PMID- 12495743
TI  - Epitope dominance, competition and T cell affinity maturation.

PMID- 12495745
TI  - Auxin transport - shaping the plant.
AB  - Plant growth is marked by its adaptability to continuous changes in environment.
      A regulated, differential distribution of auxin underlies many adaptation
      processes including organogenesis, meristem patterning and tropisms. In executing
      its multiple roles, auxin displays some characteristics of both a hormone and a
      morphogen. Studies on auxin transport, as well as tracing the intracellular
      movement of its molecular components, have suggested a possible scenario to
      explain how growth plasticity is conferred at the cellular and molecular level.
      The plant perceives stimuli and changes the subcellular position of auxin
      transport components accordingly. These changes modulate auxin fluxes, and the
      newly established auxin distribution triggers the corresponding developmental
      response.

PMID- 12495746
TI  - Shedding light on the circadian clock and the photoperiodic control of flowering.
AB  - Recently, notable progress has been made towards understanding the genetic
      interactions that underlie the function of the circadian clock in plants, and how
      these functions are related to the seasonal control of flowering time. The
      LHY/CCA1 and TOC1 genes have been proposed to participate in a negative feedback
      loop that is part of the central oscillator of the circadian clock. Furthermore,
      analysis of a flowering-time pathway has suggested how transcriptional regulation
      by the circadian clock, combined with post-transcriptional regulation by light,
      could activate proteins that control flowering time in response to appropriate
      daylengths.

PMID- 12495747
TI  - Chromatin regulation of plant development.
AB  - Chromatin remodeling factors are being identified as genetic modifiers of
      developmental mutations in plants. These mutations result in lethality in
      metazoans, whereas in plants, they are viable and affect a wide range of
      developmental and physiological processes. Recent studies have begun to define
      the many functions of chromatin remodeling factors in plants and have revealed
      apparent differences between these factors in the two kingdoms.

PMID- 12495748
TI  - Mechanisms of floral repression in Arabidopsis.
AB  - In the past two years, several early-flowering genes have been shown to encode
      putative chromatin-associated proteins in Arabidopsis. These proteins probably
      function as epigenetic silencers that repress the promotion of flowering and
      flower organ identity genes, and thereby maintain vegetative growth. As the plant
      matures, levels of the floral promoters increase despite the continued presence
      of floral repressors. High levels of the floral promoters are somehow able to
      overcome floral repression and to activate flower development. Further
      characterization of mutants that have impairments in either floral promoters or
      floral repressors revealed that these mutants not only display defects in
      flowering time but also have altered inflorescence architectures. These findings
      indicate that these flowering genes also regulate other aspects of shoot
      development and may be used to study the mechanism of shoot growth pattern.

PMID- 12495749
TI  - Pollen-tube guidance: beacons from the female gametophyte.
AB  - The sperm cell of a flowering plant cannot migrate unaided and it must be
      transported by the pollen-tube cell before successful fertilization can occur.
      The pollen tube is precisely guided to the target female gametophyte, the embryo
      sac, which contains the egg cell. The mechanism that precisely directs the pollen
      tube through the pistil to the female gametophyte has been studied for more than
      a century. There has been controversy over whether a diffusible signal attracts
      the pollen tube or whether female tissues define its path. Emerging genetic and
      physiological data show that the female gametophyte produces at least two
      directional signals, and that at least one of these signals is diffusible and
      derived from the two synergid cells.

PMID- 12495750
TI  - Endosperm: the crossroad of seed development.
AB  - The endosperm is an essential part of the seed that sustains embryo development
      and reserve storage. Several genes that are involved in endosperm differentiation
      and that have domains of expression arranged along a conserved antero-posterior
      axis have been isolated in Arabidopsis and in cereals. Endosperm polarity is
      controlled maternally by chromatin-remodeling complexes. Endosperm development
      appears to be predominantly under epigenetic controls that might be linked with
      its evolutionary origin.

PMID- 12495751
TI  - Simple hormones but complex signalling.
AB  - It has not been easy to make sense of the pleiotropic effects of plant hormones,
      especially of auxins; but now, it has become possible to study these effects
      within the framework of what we know about signal transduction in general.
      Changes in local auxin concentrations, perhaps even actively maintained auxin
      gradients, signal to networks of transcription factors, which in turn signal to
      downstream effectors. Transcription factors can also signal back to hormone
      biosynthetic pathways.

PMID- 12495752
TI  - Organ shape and size: a lesson from studies of leaf morphogenesis.
AB  - Control of the shape and size of indeterminate organs, such as roots and stems,
      is directly related to the control of the shape and size of the cells in these
      organs, as predicted by orthodox cell theory. For example, the polarity-dependent
      growth of leaf cells directly affects the polar expansion of leaves. Thus, the
      control of leaf shape is related to the control of the shape of cells within the
      leaf, as suggested by cell theory. By contrast, in determinate organs, such as
      leaves, the number of cells does not necessarily reflect organ shape or size.
      Genetic evidence shows that a compensatory system(s) is involved in leaf
      morphogenesis, and that an increase in cell volume can be triggered by a decrease
      in cell number and vice versa. Studies of chimeric leaves also suggest
      interaction between leaf cells that coordinates the behaviour of these cells at
      the organ level. Moreover, leaf size also appears to be coordinated at the whole
      plant level. The recently hypothesised neo cell theory describes how leaf shape-
      and size-control mechanisms control leaf shape at the organ-level via cell-cell
      interaction.

PMID- 12495753
TI  - Cytoskeletal control of plant cell shape: getting the fine points.
AB  - The shapes of plant cells, which are defined by their surrounding walls, are
      often important for cell function. The cytoskeleton plays key roles in
      determining plant cell shape, mainly by influencing the patterns in which wall
      materials are deposited in expanding cells. Studies employing cytoskeleton
      disrupting drugs, together with studies of mutants with cytoskeletal defects,
      have demonstrated that both microtubules and actin filaments are critical for all
      modes of cell expansion, although their precise roles remain poorly understood.
      In recent years, however, significant progress has been made in understanding the
      contributions of a variety of proteins that influence cell shape by regulating
      the organization and polymerization of cytoskeletal filaments in expanding cells.

PMID- 12495754
TI  - Cell-fate specification in the epidermis: a common patterning mechanism in the
      root and shoot.
AB  - The specification of epidermal hairs in Arabidopsis provides a useful model for
      the study of pattern formation in plants. Although the distributions of hair
      cells in the root and shoot appear quite different, recent studies show that
      pattern formation in each relies on a common cassette of transcriptional
      regulators. During development in each organ, neighboring cells compete to
      express regulators that specify the primary cell fate (including WEREWOLF
      [WER]/GLABRA1 [GL1], GL3/bHLH, TRANSPARENT TESTA GLABRA [TTG], and GL2), as well
      as those that prevent their neighbors from adopting this fate (including CAPRICE
      [CPC] and TRIPTYCHON [TRY]). The basic mechanism of lateral inhibition with
      feedback that has been uncovered by recent studies provides a conceptual
      framework for understanding how patterns of cell fate in general may be specified
      during plant development.

PMID- 12495755
TI  - Molecular regulation of leaf senescence.
AB  - Leaf senescence is a process of programmed cell death, which is induced in an age
      dependent manner and by various environmental cues. The mechanisms that regulate
      the induction and progression of leaf senescence remain unclear because of their
      complexity. However, recent genetic and reverse-genetic approaches have
      identified key components of the regulation of leaf senescence and have revealed
      glimpses of the underlying molecular mechanisms.

PMID- 12495756
TI  - QTL for plant growth and morphology.
AB  - Individuals and strains within most species exhibit heritable, and sometimes
      dramatic, differences in their growth and morphology. Advances in marker
      genotyping and statistical methods have increased the precision and sensitivity
      with which the quantitative trait loci (QTL) that are responsible for these
      differences can be mapped. This has resulted in both a more refined picture of
      the genetic architecture of many growth traits and the cloning of several of the
      genes that underlie plant QTL.

PMID- 12495757
TI  - Effect of painful heterotopic stimulation on the cutaneous silent period in the
      upper limbs.
AB  - OBJECTIVE: To evaluate the effect of heterotopic painful stimulation (HPS) on the
      cutaneous silent period (CSP) and the withdrawal flexor reflex (WFR) in the upper
      limbs, in an attempt to better identify the nociceptive component of the CSP and
      its functional relationship with the flexor reflex. METHODS: The CSP at different
      stimulus intensities, the WFR and the H/M ratio were studied in 12 healthy
      adults. Neurophysiological measurements were recorded in the following 4
      conditions: (1) control session; (2) non-painful session (dipping hand in water
      at 25 degrees C); (3) painful (cold pressor test, CPT); and (4) after-effect (3-8
      min after taking hand out of water at 5-6 degrees C). RESULTS: During the CPT,
      the duration of the high-threshold CSP was approximately 23% shorter than the
      baseline value, the high-threshold CSP latency was approximately 10% longer than
      the baseline value, and the mean RIII reflex area was approximately 40% smaller
      than the baseline reflex area (all P<0.05). A significant correlation was found
      between the percentage decrease in the CSP duration and the WFR area (r=0.61,
      P<0.05). CONCLUSIONS: Our findings indicate that the HPS specifically inhibits
      both the high-threshold CSP and the WFR, thereby providing further evidence that
      these cutaneous reflexes are functionally and anatomically related, and that they
      represent different aspects of a complex nocifensive response.

PMID- 12495758
TI  - Is Ross syndrome a dysautonomic disorder only? An electrophysiologic and
      histologic study.
AB  - OBJECTIVE: To define the involvement of peripheral nerve fibers in Ross syndrome.
      METHODS: Mechanical pain perception, tactile and thermal thresholds on hand, foot
      dorsum, thigh, median nerve orthodromic sensory conduction velocity (SCV) and
      motor conduction velocity (MCV), sural nerve antidromic SCV, peroneal nerve MCV,
      H-reflex, F-wave, median, tibial nerve somatosensory evoked potentials (SSEPs),
      perioral, hand CO(2) laser late (LEPs) and ultralate evoked potentials,
      sympathetic skin response (SSRs), cardiovascular, Minor sweat, silastic imprint,
      histamine, photopletysmographic and pupil pilocarpine tests, cutaneous
      innervation immunohistochemical techniques were studied in 3 patients with Ross
      syndrome. RESULTS: Quantitative sensory testing showed altered results in
      patients 1 and 2, and patient 3 had a slight impairment of mechanical pain
      perception. Nerve conduction, except for a median nerve distal reduction of
      sensory conduction in patient 1, F-wave and SSEP findings were normal; H-reflex
      was absent at rest in all patients. Hand LEPs were absent in patient 2, ultralate
      potentials were absent in patients 1 and 2. Skin biopsy showed a disease duration
      related reduction of unmyelinated and myelinated sensory fibers and a lack of
      unmyelinated autonomic fibers in all patients. CONCLUSIONS: Our data suggest that
      Ross syndrome is a degenerative disorder involving progressive sudomotor fibers,
      and then epidermal sensory unmyelinated and myelinated fibers.

PMID- 12495759
TI  - Temperature differences during sleep between fullterm and preterm neonates at
      matched post-conceptional ages.
AB  - OBJECTIVE: Altered physiologic behaviors during sleep have been described for
      healthy preterm neonates at post-conceptional fullterm ages. These differences
      may reflect brain dysmaturity as a result of conditions of prematurity. The
      present study examines if differences in state-specific temperature changes exist
      in a healthy preterm cohort as another expression of brain dysmaturity. METHODS:
      Rectal and skin temperatures during sleep state transitions are reported in 59
      asymptomatic post-conceptional age term infants, comparing 25 full term and 34
      preterm infants. Three-hour 24-channel electroencephalogram (EEG)-sleep studies
      were recorded for each child. One of 4 sleep states were assigned for each of
      7339 min, based on both cerebral and non-cerebral measures. For each study,
      average rectal and skin temperatures for each sleep state were calculated.
      Repeated measures MANOVA were performed using 4 explanatory variables, average
      skin and rectal temperatures and variance of rectal and skin temperatures,
      comparing preterm/fullterm status and 4 sleep states. RESULTS: Rectal temperature
      differences between neonatal cohorts during specific sleep states were noted:
      F=8.58, P<0.0001. Significant differences were noted for both average and
      variance of rectal temperatures during all 4 sleep states with higher
      temperatures in the preterm group. For all neonates, both skin and rectal
      temperature differences were also noted among sleep states (F=4.22, P<0.0004).
      Differences were specifically noted between two specific EEG segments, mixed
      frequency active sleep and trace alternant quiet sleep (P<0.0004). CONCLUSIONS:
      In summary, significant differences in temperatures were noted across sleep state
      transitions for two neonatal cohorts, with higher average rectal temperatures in
      the preterm cohort. These findings highlight an altered measure of brain function
      during sleep in preterm infants affecting temperature regulation. This altered
      physiologic behavior reflects adaptation of the infant's brain function to
      conditions of prematurity which may contribute to vulnerabilities at older ages.

PMID- 12495760
TI  - Body posture affects electroencephalographic activity and psychomotor vigilance
      task performance in sleep-deprived subjects.
AB  - OBJECTIVE: This study examined the effects of posture on electroencephalographic
      (EEG) activity and psychomotor vigilance task (PVT) performance in 16 sleep
      deprived volunteers. METHODS: EEG data were collected while participants
      completed 10 min PVTs under two counterbalanced sitting/standing conditions
      during 28 h of continuous wakefulness. RESULTS: In both the sitting and standing
      conditions, theta activity progressively increased as a function of sleep loss,
      but standing upright significantly attenuated this effect, suggesting that
      alertness was improved by the more upright posture. The PVT results showed that
      cognitive psychomotor performance was maintained at nearly well-rested levels by
      standing upright, whereas reaction time and attention noticeably deteriorated
      when participants were seated. CONCLUSIONS: These results suggest that an upright
      posture increases EEG arousal and sustained attention, indicating that postural
      manipulations can be useful for counteracting fatigue in sleep-deprived
      individuals.

PMID- 12495761
TI  - EEG findings in steroid-responsive encephalopathy associated with autoimmune
      thyroiditis.
AB  - OBJECTIVE: To analyze the electroencephalogram (EEG) findings of patients with
      steroid-responsive encephalopathy associated with autoimmune (Hashimoto)
      thyroiditis. METHODS: We reviewed 51 EEGs and the clinical records of 17 patients
      (5 men and 12 women, 27-84 years old). RESULTS: All patients had mild to severe
      generalized slowing on the EEG which corresponded to the clinical severity of the
      underlying encephalopathy. Other findings included triphasic waves, epileptiform
      abnormalities, photomyogenic response, and photoparoxysmal response. Follow-up
      EEGs of 13 patients showed slowing in 7 and a return to normal in 6. Myoclonic
      jerks were recorded during the EEG study of 8 patients but did not have an EEG
      correlate. The EEG and clinical condition improved after treatment with
      corticosteroids. When encephalopathy recurred, the EEG showed corresponding
      abnormalities. CONCLUSIONS: EEG findings in steroid-responsive encephalopathy
      associated with autoimmune thyroiditis consist mainly of slow wave abnormalities
      that reflect the degree of severity of the underlying encephalopathy. The EEG
      findings often paralleled the course of the disease, showing improvement with
      improvement in the clinical condition and worsening with recurrence of symptoms.
      SIGNIFICANCE: The EEG is helpful in evaluating and following patients with
      steroid-responsive encephalopathy associated with autoimmune thyroiditis in
      reflecting the degree of central nervous system (CNS) involvement, in determining
      whether their condition is better or worse, and in ruling out other causes of
      encephalopathy.

PMID- 12495762
TI  - Improvement in the performance of automated spike detection using dipole source
      features for artefact rejection.
AB  - OBJECTIVE: We evaluated the use of an efficient dipole source algorithm to
      improve performance of automated spike detection by identifying false detections
      caused by artefacts. METHODS: Automated spike detections were acquired from 26
      patients undergoing prolonged electroencephalograph (EEG) monitoring. Data from 6
      patients were used to develop the method and data from 20 patients were used to
      test the method. To provide a standard against which to evaluate the results, an
      electroencephalographer (EEGer) visually categorized all automated detections
      before the dipole models were calculated for all events. The event categories (as
      defined by the EEGer) were then combined with properties of the dipole model and
      features were identified that differentiated spike and artefact detections. The
      resulting method was then applied to the testing data set. RESULTS: Residual
      variance and eccentricity of the dipole models differentiated artefact and spike
      detections. A separate set of rules defining eye blink artefact was also
      developed. The combined criteria removed a mean of 53.2% of artefact from the
      testing data set. Some spike detections (4.3%) were also lost. CONCLUSIONS: The
      features of the dipole source of a detected event can be used to differentiate
      artefacts from spikes. This algorithm is computationally light and could be
      implemented on-line.

PMID- 12495763
TI  - Seizure detection in the neonatal EEG with synchronization likelihood.
AB  - OBJECTIVE: To investigate whether epileptic seizure activity can be distinguished
      from non-epileptic background activity in the neonatal electroenceplalogram
      (EEG), using synchronization likelihood as a measure of synchronization between
      EEG channels. METHODS: Forty-two 21s EEG epochs and two complete EEGs from 21
      different neonatal patients in a 12-channel bipolar recording were studied (AD
      conversion 16bit; sample frequency 200Hz; filter setting 0.5-30Hz). For EEG of
      each patient, we selected one epoch with epileptic discharges and one without.
      Synchronization was calculated in all epochs. In two complete EEGs,
      synchronization was calculated and correlated with a visual scoring of the EEG.
      RESULTS: Synchronization likelihood was higher in all the epochs with epileptic
      seizures as compared to the epochs without epileptic activity (P<0.01). When
      synchronization likelihood exceeded 0.11, the sensitivity for the presence of
      epileptic activity was 0.85 (95% confidence limits [CL(95)]=0.69-1) and the
      specificity was 0.75 (CL(95)=0.56-0.94).Analysis of EEG score and synchronization
      likelihood of two complete EEGs revealed a high correlation between the
      occurrence of epileptic seizures and elevated synchronization likelihood
      (Spearman r=0.707, P<0.001). CONCLUSIONS: The results of this study demonstrate
      that synchronization likelihood is a potential tool in the automatic monitoring
      of high-risk infants for epileptic activity on neonatal wards.

PMID- 12495764
TI  - Early ictal speech and motor inhibition in fronto-mesial epileptic seizures: a
      polygraphic study in one patient.
AB  - OBJECTIVE: To investigate ictal motor inhibition occurring during seizures in a
      patient with a tumor located in the left fronto-mesial pre-central cortex.
      METHODS: Awake and sleep video-polygraphic monitoring, recording scalp EEG and
      EMG activities from several cranial, trunk and limbs muscles, was performed in a
      patient with drug-resistant recurrent focal motor seizures before surgical
      treatment. Speech/motor tasks were repeatedly administered to the patient during
      the recording sessions in order to evaluate the occurrence of early ictal motor
      inhibition. RESULTS: Thirty-four seizures were recorded during wakefulness
      showing a stereotyped pattern of inhibition of speech and voluntary movements
      followed by sequential activation of upper limb-trunk-lower limb muscles
      contralateral to the tumor. Polygraphic recordings showed that: (1) initial
      speech and motor arrest were associated with the EMG evidence of progressive
      muscle tone suppression in cranial and right distal upper limb muscles; (2) tonic
      contraction of right deltoid, biceps brachii, intercostalis and paraspinalis
      muscles appeared after motor inhibition; (3) tonic-clonic activity in the right
      tibialis anterior muscle occurred at the end of seizures. Eleven subclinical
      seizures were recorded during sleep showing mild focal tonic EMG activity in
      right side trunk muscles. CONCLUSIONS: Our findings evidenced early and
      somatotopically organized inhibition of voluntary movement at the beginning of
      epileptic seizures with fronto-mesial onset. The demonstration that speech and
      motor arrest were associated with progressive EMG suppression in cranial and limb
      muscles supports the hypothesis of motor inhibitory seizures originating in the
      mesial aspect of pre-motor frontal cortex.

PMID- 12495765
TI  - Epileptic source localization with high density EEG: how many electrodes are
      needed?
AB  - OBJECTIVE: Electroencephalography (EEG) source reconstruction is becoming
      recognized as a useful technique to non-invasively localize the epileptic focus.
      Whereas, large array magnetoencephalography (MEG) systems are available since
      quite some time, application difficulties have previously prevented multichannel
      EEG recordings. Recently, however, EEG systems which allow for quick (10-20min)
      application of, and recording from, up to 125 electrodes have become available.
      The purpose of the current investigation was to systematically compare the
      accuracy of epileptic source localization with high electrode density to that
      obtained with sparser electrode setups. METHODS: Interictal epileptiform activity
      was recorded with 123 electrodes in 14 epileptic patients undergoing presurgical
      evaluation. Each single epileptiform potential was down sampled to 63 and 31
      electrodes, and a distributed source model (EPIFOCUS) was used to reconstruct the
      sources with the 3 different electrode configurations. The localization accuracy
      with the 3 electrode setups was then assessed, by determining the distance from
      the inverse solution, maximum of each single spike to the epileptogenic lesion.
      RESULTS: In 9/14 patients, the distance from the EEG source to the lesion was
      significantly smaller with 63 than with 31 electrodes, and increasing the number
      of electrodes to 123 increased this number of patients from 9 to 11. Simulations
      confirmed the relation between the number of electrodes and localization
      accuracy. CONCLUSIONS: The results illustrate the necessity of multichannel EEG
      recordings for high source location accuracy in epileptic patients.

PMID- 12495766
TI  - Localizing significance of temporal intermittent rhythmic delta activity (TIRDA)
      in drug-resistant focal epilepsy.
AB  - OBJECTIVE: Temporal intermittent rhythmic delta activity (TIRDA) is an EEG
      pattern characterized by sinusoidal trains of activity, ranging from 1 to 3.5 Hz,
      and well localized over the temporal regions. It is considered to be an indicator
      of temporal lobe epilepsy (TLE), but full agreement between different authors has
      still not been reached. The aim of this study was therefore to assess the role of
      TIRDA in localizing the epileptogenic zone, which was estimated using anatomo
      electro-clinical correlations obtained from non-invasive pre-surgical
      investigations, in a large group of patients affected by drug-resistant partial
      epilepsy. METHODS: The occurrence of TIRDA was investigated using a prolonged
      Video-EEG recording of 129 patients affected by drug-resistant partial epilepsy
      that underwent a non-invasive pre-surgical protocol. Patients were divided into 3
      groups: TLE only, extratemporal epilepsy, and multilobar epilepsy including
      temporal lobe. According to the epileptogenic zone identified using anatomo
      clinical-radiological correlations, 3 different subgroups of TLE were identified:
      mesial, lateral, and mesio-lateral. Statistical analysis was performed in order
      to evaluate the relationship between TIRDA and the epileptogenic zone, and
      neuroradiological, neuropathological, EEG interictal and ictal findings. RESULTS:
      The pattern of TIRDA was observed in 52 out of the 129 (40.3%) patients studied.
      Significant correlations were found between TIRDA and: (i) mesial and mesio
      lateral TLE; (ii) mesial temporal sclerosis; (iii) interictal epileptiform
      discharge localized over the anterior temporal regions; and (iv) 5-9 Hz temporal
      ictal discharge. CONCLUSIONS: Our research shows that TIRDA plays a role in
      localizing the epileptogenic zone, suggesting that this pattern might be
      considered as an EEG marker of an epileptogenesis that involves the mesial
      structures of the temporal lobe. However, further studies investigating the
      relationship between intracranial EEG monitoring and simultaneous scalp EEG
      recording are needed in order to confirm our findings and improve our
      understanding of the significance of TIRDA.

PMID- 12495767
TI  - Phase synchronization of the ongoing EEG and auditory EP generation.
AB  - OBJECTIVE: We investigated the role of phase synchronization of the spontaneous
      electroencephalogram (EEG) in auditory evoked potential (EP) generation in a
      sample of healthy individuals. METHODS: Auditory responses were obtained from 20
      healthy subjects following a double stimulus paradigm, using two identical tone
      bursts (S1 and S2) separated by 0.5s. Single-trial auditory evoked potentials
      were decomposed into sinusoidal, exponentially decaying/increasing components
      using the piecewise Prony method (PPM). Pre- and post-stimulus phase histograms
      were compared to determine the degree of phase synchronization produced by
      auditory stimulation. RESULTS: Analysis of single responses revealed that the S1
      stimuli produced phase synchronization in the 2-8Hz frequency range, with little
      or no concomitant amplitude increase. A significantly reduced phase effect was
      seen in response to S2 stimuli. CONCLUSIONS: Stimulus-induced phase
      synchronization of the ongoing EEG is a major mechanism for the generation of
      auditory EP components with a latency in the 50-250ms range. SIGNIFICANCE: The
      fact that the EP components accessed here are generated through phase
      synchronization implies that the ensemble-averaged EP will not resemble the
      single trial response, and it would certainly be misleading to consider the
      single trial response as an amplitude-scaled version of the ensemble average.

PMID- 12495768
TI  - Conduction velocity of nerve and muscle fiber action potentials after a space
      mission or a bed rest.
AB  - OBJECTIVE: The purpose of the present investigation was to study the readaptation
      of a human muscle after a prolonged stay in microgravity and after a bed rest of
      several months. METHODS: The surface electromyogram of the soleus muscle was
      recorded in 6 cosmonauts and 6 bed rest subjects at 5 different torque levels
      and, in addition, the direct muscle responses (M responses) to supramaximal
      stimulation of the posterior tibial nerve were also recorded in the bed rest
      subjects. In a supplementary experiment in normal subjects, M response was
      recorded with an array of electrodes. RESULTS: The median frequency (MF) of the
      power spectrum of the surface electromyogram was reduced, at all torque levels,
      immediately after the test period. In the bed rest subjects, the latency of the M
      response peaks and the inter-peak interval increased during the test period.
      Recovery to normal occurred within about 10 days. In the normal subjects, the
      peaks of the M response were conducted along the muscle with a velocity between
      21 and 30 m/s. CONCLUSIONS: All these results point to a reduction of the
      conduction velocity in the branching axon terminals and in the muscle fibers
      during space missions and bed rest.

PMID- 12495769
TI  - Verification of the median-to-ulnar and ulnar-to-median nerve motor fiber
      anastomosis in the forearm: an electrophysiological study.
AB  - OBJECTIVE: To estimate the real occurrence of the motor median-to-ulnar nerve
      anastomosis in the proximal forearm (Martin-Gruber anastomosis, MGA), as its
      frequency varies between 6 and 44% in the literature and to investigate the
      incidence of the ulnar-to-median nerve anastomosis in the distal forearm.
      METHODS: Compound muscle action potentials (CMAP) recorded over thenar,
      hypothenar, and first dorsal interosseus muscle on median or ulnar nerve
      stimulation at wrist and elbow and collision blocks of the median and ulnar nerve
      were compared in a group of 50 healthy volunteers. Particular precautions were
      undertaken in order to avoid false positive results due to stimulus spread to the
      neighboring nerve. Cases of uncertain MGA were classified as either MGA or non
      MGA on the basis of posterior probabilities estimated by discriminant analysis.
      RESULTS: The estimated frequency of MGA was 54% using the potential comparison
      method and 46% using the collision technique. An ulnar-to-median nerve
      anastomosis was not found in any subject. CONCLUSIONS: While the MGA is very
      common, the ulnar-to-median nerve anastomosis is a rarity. Standard nerve
      conduction studies of the median nerve with CMAP recordings solely over thenar
      will detect less than 14% of MGA cases.

PMID- 12495770
TI  - Movement-related cortical potentials in myotonic dystrophy.
AB  - OBJECTIVE: To investigate a possible deficit of the voluntary movement mechanism
      within the central nervous system (CNS) in patients with myotonic dystrophy
      (MyD). METHODS: Movement-related cortical potentials preceding voluntary
      extension of the right middle and index fingers were studied in 9 patients with
      MyD and compared with those in 11 age-matched healthy subjects and 9 age-matched
      patients with other neuromuscular disorders (NMDs). RESULTS: The amplitudes of
      Bereitschaftspotential was smaller in MyD patients than in age-matched controls
      and age-matched patients with other NMDs although there was no statistically
      significant difference. The amplitude of negative slope was significantly smaller
      in MyD patients than in age-matched controls and age-matched patients with other
      NMDs. Clinical findings such as age, disease duration, degree of motor impairment
      and cognitive function had no effect on the individual electrophysiological
      parameters. CONCLUSIONS: The present results suggest that subclinical
      abnormalities exist in CNS function associated with motor preparation and
      execution, which is independent of muscle weakness.

PMID- 12495771
TI  - Basic mechanisms of central rhythms reactivity to preparation and execution of a
      voluntary movement: a stereoelectroencephalographic study.
AB  - OBJECTIVE: To localize the sources of mu, beta and gamma rhythms and to explore
      the functional significance of their reactivity. METHODS: We used the method of
      quantification of event-related desynchronization (ERD) and synchronization (ERS)
      to analyze the reactivity of intracerebral rhythms recorded in
      stereoelectroencephalography within the sensorimotor areas during the preparation
      and the execution of a simple self-paced hand movement. We recorded 3 epileptic
      subjects who were explored before a surgical treatment. RESULTS: An ERD of mu and
      beta rhythms has been recorded before the movement onset in the precentral gyrus,
      spreading then to the postcentral gyrus and to the frontal medial cortex. The
      frontal lateral cortex was inconstantly involved during the movement. The
      movement offset was followed by an important and focused beta ERS which was found
      within the pre- and post-central gyrus and the frontal medial cortex. Within the
      beta band, we observed several narrower bands with different reactivities and
      locations. Focused gamma reactivity was also found in the precentral and
      postcentral gyri. CONCLUSIONS: The reactivities of mu and beta rhythms are
      different but their locations overlap. Mu ERD is a diffuse phenomenon that
      reflects the activation of all the sensorimotor areas during a simple movement.
      Beta band is likely to be composed of different rhythms with different functional
      significance. The primary motor area seems to contain two distinct areas with
      different reactivity to the movement preparation and execution.

PMID- 12495772
TI  - Abnormal gating of somatosensory inputs in essential tremor.
AB  - OBJECTIVE: To study whether sensorimotor cortical areas are involved in Essential
      Tremor (ET) generation. BACKGROUND: It has been suggested that sensorimotor
      cortical areas can play a role in ET generation. Therefore, we studied median
      nerve somatosensory evoked potentials (SEPs) in 10 patients with definite ET.
      METHODS: To distinguish SEP changes due to hand movements from those specifically
      related to central mechanisms of tremor, SEPs were recorded at rest, during
      postural tremor and during active and passive movement of the hand. Moreover, we
      recorded SEPs from 5 volunteers who mimicked hand tremor. The traces were further
      submitted to dipolar source analysis. RESULTS: Mimicked tremor in controls as
      well as active and passive hand movements in ET patients caused a marked
      attenuation of all scalp SEP components. These SEP changes can be explained by
      the interference between movement and somatosensory input ('gating' phenomenon).
      By contrast, SEPs during postural tremor in ET patients showed a reduction of
      N20, P22, N24 and P24 cortical SEP components, whereas the fronto-central N30
      wave remained unaffected. CONCLUSIONS: Our findings suggest that in ET patients
      the physiological interference between movement and somatosensory input to the
      cortex is not effective on the N30 response. This finding thus indicates that a
      dysfunction of the cortical generator of the N30 response may play a role in the
      pathogenesis of ET.

PMID- 12495773
TI  - Modulation of excitability of human motor cortex (M1) by 1 Hz transcranial
      magnetic stimulation of the contralateral M1.
AB  - OBJECTIVE: Previous studies demonstrated that single-pulse transcranial magnetic
      stimulation (TMS) of one motor cortex (M1) exerts a brief inhibitory effect on
      the contralateral M1. The purpose of this study was to test the hypothesis that
      30min of 1Hz TMS of M1 will result in a lasting increase in excitability in the
      contralateral M1. METHODS: Healthy volunteers were tested on 2 separate days,
      before (baseline) and after one of two interventions: (a) stimulation of M1 with
      1Hz TMS for 30min at 115% of resting motor threshold, and (b) sham stimulation.
      Recruitment curves to TMS, pinch force, and simple reaction time were assessed in
      the hand contralateral to the unstimulated motor cortex. RESULTS: The main
      finding of this study was that 30min of 1Hz significantly increased recruitment
      curves in the contralateral motor cortex in the real stimulation condition
      relative to sham (P<0.005, factorial analysis of variance (ANOVA)). This change
      outlasted the stimulation period for at least 15min and occurred in the absence
      of changes in pinch force or reaction time. CONCLUSIONS: These results raise the
      potential for inducing lasting modulation of excitability in M1 by 1Hz TMS of the
      other M1, a phenomenon possibly reflecting modulation of interhemispheric
      interactions. SIGNIFICANCE: It is conceivable that 1Hz TMS applied to M1 may be
      used to modulate excitability in the opposite motor cortex for therapeutic
      purposes.

PMID- 12495774
TI  - Electrophysiological evidence of abnormal activation of the cerebral network of
      involuntary attention in alcoholism.
AB  - OBJECTIVE: Increased distractibility is a common impairment in alcoholism, but
      objective evidence has remained elusive. Here, a task designed to investigate
      with event-related brain potentials (ERPs) the neural mechanism underlying
      distraction was used to show abnormal involuntary orienting of attention in
      chronic alcoholism. METHODS: Fifteen alcoholics and 17 matched healthy controls
      were instructed to ignore auditory stimuli while concentrating in the
      discrimination of immediately following visual stimuli. The auditory sequences
      contained repetitive standard tones occasionally replaced by deviant tones of
      slightly higher frequency, or by complex novel sounds. RESULTS: Deviant tones and
      novel sounds distracted visual performance, i.e. increased reaction time to
      visual stimuli, similarly in patients and controls. Compared to controls,
      however, alcoholics showed ERP abnormalities, i.e. enhanced P3a amplitudes over
      the left frontal region, and a positive posterior deflection instead of the
      frontally distributed reorienting negativity (RON). CONCLUSIONS: The enhanced P3a
      to novelty and subsequent positive wave instead of RON in alcoholics suggests
      encoding into working memory of task-irrelevant auditory events and provides
      neurophysiological markers of impaired involuntary attention mechanisms in
      chronic alcoholism.

PMID- 12495775
TI  - Are the neurophysiological techniques useful for the diagnosis of diaphragmatic
      impairment in multiple sclerosis (MS)?
AB  - OBJECTIVE: To characterize cortico-diaphragmatic pathway involvement in multiple
      sclerosis (MS) by means of transcranial magnetic stimulation (TMS), and verify
      its clinical impact. METHODS: TMS from diaphragm (Dia), and abductor digiti
      minimi (AbdV degrees ) was performed in 26 MS patients. Phrenic nerve (PN)
      conduction study was also performed. Expanded disability status scale (EDSS) and
      fatigue descriptive scale (FDS) were measured. Forced vital capacity (FVC),
      forced expiratory volume at the first second (FEV1), peak expiratory flow (PEF)
      were tested: the predicted percentage value (% pred) was considered. RESULTS:
      Cortical motor evoked potential (Cx-MEP) latency and central motor conduction
      time (CMCT) were prolonged, respectively, in 31 and 23% of patients from Dia, in
      76 and 79% from AbdV degrees. PN-compound motor action potential (CMAP) was
      normal. EDSS correlated to Cx-MEP from AbdV degrees (P<0.01), and PN-CMAP
      amplitude (P<0.05), FEV1 % pred (P<0.01), PEF % pred (P<0.01). PN-CMAP amplitude
      correlated to FVC % pred P=0.05, FEV1 % pred P<0.01, PEF % pred P<0.01. Fatigue
      was related to AbdV degrees Cx-MEP and CMCT (P<0.05 and P<0.01). CONCLUSIONS:
      Cortico-diaphragmatic pathway is impaired only in a minority of MS patients. Lack
      of correlation between TMS findings from Dia and respiratory tests argues against
      its routinary use to detect subclinical respiratory alterations. Fatigue seems to
      be related to the motor impairment rather than to respiratory distress.

PMID- 12495777
TI  - Effects of free fatty acids on gluconeogenesis and glycogenolysis.

PMID- 12495778
TI  - Real-time measurement of nitric oxide by luminol-hydrogen peroxide reaction in
      crystalloid perfused rat heart.
AB  - The objective of this study was to develop an assay system that allows continuous
      monitoring of nitric oxide (NO) released from crystalloid perfused hearts. We
      utilized chemiluminescence reaction between NO and luminol-H(2)O(2) to quantify
      the NO level in coronary effluent. Isolated rat hearts were subjected to ordinary
      Langendorff's perfusion, and the right ventricle was cannulated to sample
      coronary effluent. After equilibration, the coronary flow rate was set constant
      and the hearts were paced at 300 bpm. Coronary effluent was continuously sampled
      and mixed with the chemiluminescent probe containing 0.018 mmol/l luminol plus 10
      mmol/l H(2)O(2). Chemiluminescence from the mixture of coronary effluent and the
      probe was continuously measured. NO concentration was calibrated by various
      concentrations (0.5-400 pmol/l) of standard NO solution. The lower detection
      limit of NO was 1 pmol/l. Basal NO release from isolated perfused rat heart was
      0.41 +/- 0.17 pmol/min/g of heart weight, and that was significantly suppressed
      by 0.1 mmol/l of L-NAME to 0.18 +/- 0.10 pmol/min/g of heart weight (n = 7).
      Application of 0.1 and 0.3 micromol/l acetylcholine increased NO level in the
      coronary effluent, in a concentration-dependent manner, from 6.6 +/- 1.7 in a
      baseline condition to 16.3 +/- 7.4 and 30.3 +/- 16.1 pmol/l at each peak,
      respectively. Thrombin at 1 and 10 U/ml also increased NO level from 17.6 +/- 4.3
      in control to 35.5 +/- 10.4 and 48.7 +/- 8.7 pmol/l at each peak, respectively (n
      = 7). Thus, this assay system is applicable to the continuous real-time
      measurement of NO released from crystalloid perfused hearts, and it may be useful
      for the study of physiological or pathophysiological role of NO in coronary
      circulation.

PMID- 12495779
TI  - Hormonal changes during 17 days of head-down bed-rest.
AB  - We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on
      the daily rhythms of the hormones involved in hydroelectrolytic regulation. This
      HDBR study was designed to mimic a real space flight. Urine samples were
      collected at each voiding before, during and after HDBR. Urinary excretion of
      Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and
      Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion
      during the night of HDBR was noted. For GH, a rhythm was found before and during
      HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6
      Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the
      experiment without any modification to the level of phase. A decrease during the
      night was noted for normetadrenaline urinary derivates, but only during the HDBR.

PMID- 12495780
TI  - A-350619: a novel activator of soluble guanylyl cyclase.
AB  - Nitric oxide (NO) is a key mediator in many physiological processes and one of
      the major receptors through which NO exerts its effects is soluble guanylyl
      cyclase. Guanylyl cyclase converts GTP to cyclic GMP as part of the cascade that
      results in physiological processes such as smooth muscle relaxation,
      neurotransmission, inhibition of platelet aggregation and immune response. The
      properties of A-350619, a novel soluble guanylyl cyclase activator, were examined
      to determine the modulatory effect on the catalytic properties of soluble
      guanylyl cyclase. A-350619 increased V(max) from 0.1 to 14.5 micromol/min/mg (145
      fold increase), and lowered K(m) from 300 to 50 microM (6 fold decrease). When YC
      1 (another sGC activator) and A-350619 were combined, a 156 fold increase in
      V(max) and a 5 fold decrease in Km were observed, indicating that the modulation
      of the enzyme brought about by YC-1 and A-350619 are not additive, suggesting a
      common binding site. Activation of soluble guanylyl cyclase by A-350619 was
      partially inhibited by ODQ, a specific inhibitor of soluble guanylyl cyclase by
      oxidation of the enzyme heme. YC-1 and A-350619 after pre-treatment with N-omega
      nitro-L-arginine, an NO-synthase inhibitor, relaxed cavernosum tissue strips in a
      dose-dependent manner with EC(50) of 50 microM and 80 microM, respectively.
      Addition of SNP potentiated the relaxation effect of YC-1 and A-350619, shifting
      the dose-response curve to the left to 3 microM and 10 microM, respectively.
      Consistent with its biochemical activity, A-350619 (1 micromol/kg) alone induced
      penile erection in a conscious rat model. Activation of soluble guanylyl cyclase
      in cavernosum tissue as an alternate method of enhancing the effect of NO may
      provide a novel treatment of sexual dysfunction.

PMID- 12495781
TI  - Changes of heme oxygenase-carbon monoxide system in vascular calcification in
      rats.
AB  - The aim of the present study was to investigate the change in heme oxygenase (HO)
      carbon monoxide (CO)-cyclic guanosine monophosphate (cGMP) pathway in vascular
      calcification. Vascular calcification model was established in rats by using
      vitamin D(3) and nicotine. Vascular calcium content, alkaline phosphatase (ALP)
      activity, HO activity, HbCO formation and content of cGMP in vessels were
      measured. Immunochemistry (IH) for HO 1 expression and in situ hybridization
      (ISH) for HO 1 mRNA were observed. Compared to those of control rats, the aortic
      calcium content and vascular ALP activity in rats of the calcified group (VDN
      group) were obviously increased, but HO 1 activity, CO concentration and cGMP
      content in vessels of rats in VDN group were markedly decreased. Expressions of
      HO-1 protein and mRNA were significantly decreased compared to control rats.
      Vascular calcification might induce a down regulation in vascular HO-CO-cGMP
      pathway.

PMID- 12495782
TI  - Cardiac electrophysiological modulation by NS-7, a novel neuroprotective drug, of
      guinea pig ventricular muscles.
AB  - Effects of NS-7 (1 to 100 microM), a novel neuroprotective drug, on the action
      potentials in guinea pig ventricular muscles were investigated at different
      stimulation frequencies, different extracellular Ca(2+) concentrations ([Ca](o))
      and in the presence of inhibitors for selective delayed rectifier K(+) channels.
      A conventional microelectrode technique was carried out. NS-7 caused inhibitory
      actions on the action potential configuration in a concentration-dependent
      manner. NS-7 at less concentrations than 30 microM did not affect, but at 100
      microM decreased the action potential amplitude (APA) and the maximum rate of
      depolarization (V(max)) by 11.1 +/- 2.3% (n = 14, P < 0.05) and by 24.3 +/- 2.6%
      (n = 14, P < 0.01), respectively. NS-7 at 100 microM also prolonged the 75 and
      90% repolarizations of action potential duration (APD(75) and APD(90)) by 14.5 +/
      2.2% (n = 14, P < 0.05) and 20.2 +/- 2.4% (n = 14, P < 0.01), respectively, but
      it at any concentrations failed to affect the 50% repolarization of action
      potential duration (APD(50)). The resting potential was unaffected. These
      responses were almost reversible after 10-to 20-min washout. The stronger
      inhibition was caused at higher frequencies of stimulation. NS-7 prolonged the
      APD at lower [Ca](o) than 3.6 mM. In the presence of 5 microM E-4031 or 30 microM
      293B, NS-7 increased further the APD. These results indicate that NS-7 at
      relatively higher concentrations produced inhibitory actions on the cardiac
      muscles, and that the APD prolongation and the V(max) inhibition induced by NS-7
      are dependent on stimulation frequencies, but are independent of [Ca](o) levels,
      resulting in exhibition of its cardioprotective action.

PMID- 12495783
TI  - Urotensin II-induced activation of extracellular signal-regulated kinase in
      cultured vascular smooth muscle cells: involvement of cell adhesion-mediated
      integrin signaling.
AB  - Urotensin II (UII), a cyclic dodecapeptide, is a potent mammalian
      vasoconstrictive substance recently shown to induce proliferation of vascular
      smooth muscle cells (VSMCs). However, little is known about mechanisms involved
      in UII-induced mitogenic response such as cell proliferation. To investigate the
      intracellular signaling pathways involved in this process, we examined the
      effects of UII on activation of extracellular signal-regulated kinase (ERK) and
      focal adhesion kinase (FAK) in VSMCs. UII stimulated in time- and dose-dependent
      manners the phosphorylation level of ERK. In contrast, UII failed to alter the
      phosphorylation level of FAK. Although angiotensin II-induced ERK phosphorylation
      was noted even in suspended cells, UII failed to induce an increase in ERK
      phosphorylation in such cells. On the other hand, UII induced an increase in the
      phosphorylation level of ERK, but not FAK, in cells adherent to fibronectin.
      Furthermore, UII-induced proliferation of VSMCs was inhibited by ERK kinase
      inhibitor PD98059. Our results suggested that activation of integrin-mediated
      signaling pathways play a critical role in UII-induced phosphorylation of ERK,
      leading to proliferation of VSMCs, which does not involved increased
      phosphorylation of FAK.

PMID- 12495784
TI  - Protection of tea melanin on hydrazine-induced liver injury.
AB  - The protective activity of melanin derived from tea (MDFT) was studied using
      hydrazine as a DNA-reactive chemical agent. Intra-peritoneal administration of
      MDFT at the doses of 5 or 20 mg/kg dose-dependently prevented liver toxicity
      induced by hydrazine in rats. It normalized rises in serum alanine transferase
      activity and a decrease in the glutathione level in the liver. It also reduced
      the hepatic malondialdehyde concentration. Monitoring the intensity of
      chemiluminescence showed that MDFT could prevent the production of free radicals
      that are generated owing to metabolic transformation of hydrazine. It also
      prevented the formation 8-hydroxy-deoxyguanosine (8-OH-dG) DNA adducts. The
      results obtained in vivo and in vitro suggest that MDFT confers marked protection
      of the liver against hydrazine-induced oxidative toxicity.

PMID- 12495785
TI  - Effects of green tea polyphenols on dopamine uptake and on MPP+ -induced dopamine
      neuron injury.
AB  - As antioxidants, polyphenols are considered to be potentially useful in
      preventing chronic diseases in man, including Parkinson's disease (PD), a disease
      involving dopamine (DA) neurons. Our studies have demonstrated that polyphenols
      extracted from green tea (GT) can inhibit the uptake of 3H-dopamine (3H-DA) and 1
      methyl-4-phenylpyridinium (MPP(+)) by DA transporters (DAT) and partially protect
      embryonic rat mesencephalic dopaminergic (DAergic) neurons from MPP(+)-induced
      injury. The inhibitory effects of GT polyphenols on 3H-DA uptake were determined
      in DAT-pCDNA3-transfected Chinese Hamster Ovary (DAT-CHO) cells and in striatal
      synaptosomes of C57BL/6 mice in vitro and in vivo. The inhibitory effects on 3H
      MPP(+) uptake were determined in primary cultures of embryonic rat mesencephalic
      DAergic cells. Inhibition of uptake for both 3H-DA and 3H-MPP(+) was dose
      dependent in the presence of polyphenols. Incubation with 50 microM MPP(+)
      resulted in a significant loss of tyrosine-hydroxylase (TH)-positive cells in the
      primary embryonic mesencephalic cultures, while pretreatment with polyphenols (10
      to 30 microg/ml) or mazindol (10 microM), a classical DAT inhibitor,
      significantly attenuated MPP(+)-induced loss of TH-positive cells. These results
      suggest that GT polyphenols have inhibitory effects on DAT, through which they
      block MPP(+) uptake and protect DAergic neurons against MPP(+)-induced injury.

PMID- 12495786
TI  - Effects of stress and tranylcypromine on amphetamine-induced locomotor activity
      and GABA(B) receptor function in rat brain.
AB  - Modification in gamma-aminobutyric acid-B (GABA(B)) receptors may contribute to
      the symptoms of some neurological and psychiatric disorders and to the clinical
      response to psychotherapeutics. The present study was undertaken to determine
      whether chronic administration of tranylcypromine (TCP), an antidepressant, and
      chronic stress influence GABA(B) receptor function in rat brain. The results
      indicate that TCP treatment, but not stress, increases GABA(B) receptor activity
      in the cerebral cortex, as measured by baclofen-stimulated GTPgammaS binding. In
      addition, chronic administration of TCP enhances significantly the locomotor
      response to a single dose of amphetamine, an effect that is abolished by
      restraint stress. These results indicate that although TCP administration
      modifies brain GABA(B) receptor activity, which may contribute to the
      antidepressant response to this agent, this effect is unrelated to the
      interaction of stress and TCP treatment on the locomotor response to amphetamine.

PMID- 12495787
TI  - Trends in inpatient detoxification services, 1992-1997.
AB  - The paper examines trends in the use of inpatient substance abuse detoxification
      provided at general hospitals using data from the Healthcare Utilization and Cost
      Project - National Inpatient Survey. Most persons who received inpatient
      detoxification did not also receive rehabilitation while an inpatient. The
      percentage receiving rehabilitation declined between 1992 and 1997 from 38.9% to
      21.1%. The decrease in the probability of receiving rehabilitation occurred
      across gender, age, region, insurance status, income levels, diagnoses, admission
      source, and discharge destination. Two other notable trends are that average
      length of stay for detoxification dropped by one third over the six-year period,
      from 7.7 days to 5.2 days and the percentage of admissions through the emergency
      room increased from 35.6% to 40.1%. Detoxification offers an opportunity to link
      patients with rehabilitation. This analysis indicates that those opportunities
      may be missed.

PMID- 12495788
TI  - The effect of treatment completion and length of stay on employment and crime in
      outpatient drug-free treatment.
AB  - Length of stay in treatment has been found to be a significant predictor of
      positive post-treatment outcomes, such as decreases in unemployment and crime.
      However, length of stay may be an incomplete predictor of successful treatment.
      Surprisingly, few studies have examined whether completing treatment in addition
      to length of stay is an important factor in explaining positive treatment
      outcomes. The objective of our study is to examine the effect that treatment
      completion and length of stay have on post-treatment employment and crime for
      patients in outpatient drug-free treatment, the largest treatment modality in the
      United States. We use conditional logit and multiple regression models with
      program-level indicator variables (fixed effects) to estimate the effect of
      treatment completion and length of stay on employment and crime controlling for
      drug use severity, previous treatment history, and other patient demographics.
      Data are from the National Treatment Improvement Evaluation Study and include 986
      adults enrolled in outpatient drug-free programs across the United States. We
      find that treatment completion and length of stay are significantly related to
      post-treatment employment. Holding length of stay constant, the occurrence of
      employment at follow-up among patients who complete their planned treatment is
      almost 2 times that of patients who do not complete treatment. However, treatment
      completion did not have a statistically significant effect on the probability of
      post-treatment crime. Although our results are mixed, these findings suggest that
      greater attention should be placed on evaluating the importance of both length of
      stay and treatment completion in treatment outcome studies.

PMID- 12495789
TI  - Ketamine psychotherapy for heroin addiction: immediate effects and two-year
      follow-up.
AB  - Seventy detoxified heroin-addicted patients were randomly assigned to one of two
      groups receiving ketamine psychotherapy (KPT) involving two different doses of
      ketamine. The patients of the experimental group received existentially oriented
      psychotherapy in combination with a hallucinogenic ("psychedelic") dose of
      ketamine (2.0 mg/kg im). The patients of the control group received the same
      psychotherapy combined with a low, non-hallucinogenic (non-psychedelic), dose of
      ketamine (0.2 mg/kg im). Both the psychotherapist and patient were blind to the
      dose of ketamine. The therapy included preparation for the ketamine session, the
      ketamine session itself, and the post session psychotherapy aimed to help
      patients to integrate insights from their ketamine session into everyday life.
      The results of this double blind randomized clinical trial of KPT for heroin
      addiction showed that high dose (2.0 mg/kg) KPT elicits a full psychedelic
      experience in heroin addicts as assessed quantitatively by the Hallucinogen
      Rating Scale. On the other hand, low dose KPT (0.2 mg/kg) elicits "sub
      psychedelic" experiences and functions as ketamine-facilitated guided imagery.
      High dose KPT produced a significantly greater rate of abstinence in heroin
      addicts within the first two years of follow-up, a greater and longer-lasting
      reduction in craving for heroin, as well as greater positive change in nonverbal
      unconscious emotional attitudes than did low dose KPT.

PMID- 12495790
TI  - Gender differences in predictors of initiation, retention, and completion in an
      HMO-based substance abuse treatment program.
AB  - We studied gender differences in treatment process indicators among 293 HMO
      members recommended for substance abuse treatment. Treatment initiation,
      completion, and time spent in treatment did not differ by gender, but factors
      predicting these outcomes differed markedly. Initiation was predicted in women by
      alcohol diagnoses; in men, by being employed or married. Failure to initiate
      treatment was predicted in women by mental health diagnoses; in men, by less
      education. Treatment completion was predicted in women by higher income and
      legal/agency referral; in men, by older age. Failure to complete was predicted in
      women by more dependence diagnoses and higher Addiction Severity Index Employment
      scores; in men, by worse psychiatric status, receiving Medicaid, and motivation
      for entering treatment. More time spent in treatment was predicted, in women, by
      alcohol or opiate diagnoses and legal/agency referral; in men, by fewer mental
      health diagnoses, higher education, domestic violence victim status, and prior 12
      step attendance. Clinical implications of results are discussed.

PMID- 12495791
TI  - Dual Diagnosis Motivational Interviewing: a modification of Motivational
      Interviewing for substance-abusing patients with psychotic disorders.
AB  - Motivational Interviewing (MI) is a brief treatment approach for helping patients
      develop intrinsic motivation to change addictive behaviors. While initially
      developed to target primary substance using populations, professionals are
      increasingly recognizing the promise this approach has for addressing the
      motivational dilemmas faced by patients who have co-occurring psychiatric and
      psychoactive substance use disorders. Unfortunately, this recognition has not
      lead to a clear explication of how MI might be adopted for specific diagnostic
      populations of dually diagnosed patients. In this article we describe how we have
      applied the principles and practices of MI to patients who have psychotic
      disorders and co-occurring drug or alcohol use problems. Specifically, we provide
      two supplemental guidelines to augment basic MI principles (adopting an
      integrated dual diagnosis approach, accommodating cognitive impairments and
      disordered thinking). We present recommended modifications to primary MI skill
      sets (simplifying open-ended questions, refining reflective listening skills,
      heightening emphasis on affirmation, integrating psychiatric issues into
      personalized feedback and decisional balance matrices). Finally, we highlight
      other clinical considerations (handling psychotic exacerbation and crisis events,
      recommended professional qualifications) when using MI with psychotic disordered
      dually diagnosed patients.

PMID- 12495792
TI  - Characteristics, beliefs, and practices of community clinicians trained to
      provide manual-guided therapy for substance abusers.
AB  - The successful dissemination of empirically supported addiction therapies to
      community providers requires an appreciation of the characteristics of those
      practitioners who might be willing participants in this process of technology
      transfer. Clinicians (N = 66) from 11 community treatment programs associated
      with six research-clinic partnerships of the National Drug Abuse Clinical Trials
      Network volunteered to be trained in Motivational Interviewing or Motivational
      Enhancement Therapy (MET/MI) and were assessed prior to training. The sample of
      clinicians was heterogeneous in education and credentials, had a high level of
      counseling experience, reported using a wide range of counseling techniques and
      orientations, but had limited prior exposure to MET/MI or to the use of treatment
      manuals of empirically supported therapies. In general, many of the clinicians
      reported beliefs and techniques that were consistent with their stated
      theoretical orientation and recovery status. Relatively few participants reported
      relying on one dominant orientation or set of techniques.

PMID- 12495793
TI  - Patient attitudes concerning the inclusion of spirituality into addiction
      treatment.
AB  - The purpose of this exploratory study was 3-fold: (a) to determine how
      'spirituality' is defined by inner-city HIV-positive drug users; (b) to determine
      perceived relationships between spirituality and abstinence, harm reduction, and
      health promotion; and (c) to assess interest in a spirituality-based
      intervention. Opioid-dependent patients enrolled in an inner-city methadone
      maintenance program participated in the study; 21 participated in focus groups
      and 47 completed a questionnaire. In the focus groups, two predominant themes
      emerged: spirituality as a source of strength/protection of self, and
      spirituality as a source of altruism/protection of others. A large majority of
      the larger sample expressed an interest in receiving spirituality-focused
      treatment, reporting that such an intervention would be helpful for reducing
      craving and HIV risk behavior, following medical recommendations, and increasing
      hopefulness. African American women perceived spirituality as more helpful in
      their recovery than did African American men.

PMID- 12495794
TI  - Do patients' perceptions of their counselors influence outcomes of drug
      treatment?
AB  - This prospective longitudinal study examined the influence of patients'
      perceptions of their counselors on their lengths of stay in treatment and
      subsequent treatment outcomes. Patients (N = 511) were recruited from 19
      substance abuse treatment programs in Los Angeles County. While in treatment,
      patients rated their counselors on 14 aspects (e.g., empathy, directiveness); 1
      year later they were interviewed for follow-up outcomes. Multiple regression
      analyses were conducted using patients' ratings of their counselors to assess the
      impact of these ratings on treatment retention and follow-up outcomes (i.e.,
      severity of alcohol use, drug use, and psychiatric status as measured by the
      Addiction Severity Index). Results revealed that patients' positive perceptions
      of their counselors were significantly associated with a longer length of stay in
      treatment for the outpatient drug free/day treatment and residential treatment
      subsamples. Patients' positive perceptions were also significantly associated
      with better psychiatric functioning at follow-up, but had a limited relationship
      to severity of alcohol use and no relation to severity of drug use.

PMID- 12495795
TI  - A novel cognitive-behavioral approach for treatment-resistant drug dependence.
AB  - Despite the application of treatments that combine methadone administration,
      weekly counseling, and contingency reinforcement strategies, many opiate
      dependent patients continue illicit drug use. In this controlled study we piloted
      a novel cognitive-behavioral treatment (CBT) designed to reduce illicit drug use
      among patients receiving methadone treatment. The treatment targeted the
      reduction of sensitivity to interoceptive cues associated with drug craving, and
      trained alternative responses to these cues. Patients (N = 23) were randomly
      assigned to either this novel CBT program or a program of increased counseling,
      such that the two programs of treatment were equated for therapist contact,
      assessment time, and contingency-reinforcement strategies. We found that,
      compared to a doubling of contact with their outpatient counselor, the new
      program was associated with significantly greater reductions in illicit drug use
      for women, but not for men. Reasons for differential performance by women and men
      and future directions for this new treatment are discussed.

PMID- 12495796
TI  - Adoption of drug avoidance activities among patients in contingency management
      and cognitive-behavioral treatments.
AB  - This study of 97 cocaine-dependent subjects assessed differences in the effects
      of cognitive behavioral therapy (CBT) and non-CBT treatments, such as contingency
      management (CM) and methadone maintenance, on patients' adoption of drug
      avoidance activities (DAA) after treatment, and whether the adoption of these
      activities was associated with sustained reductions in cocaine use during the
      follow-up period. Subjects who had been exposed to CBT reported more frequent
      engagement in drug-use avoidance activities at treatment end and at the 1-year
      follow-up than did subjects assigned to either the CM or control conditions. The
      composite DAA scores were significantly related to cocaine abstinence at both
      follow-up contacts. This finding suggests the importance of adopting a range of
      avoidance activities and engaging in them frequently, rather than relying on any
      single activity. Further, a series of multivariate regression models revealed
      that a subject's total DAA score accounted for more variance than did treatment
      group assignment in predicting reduced cocaine use over the 1-year follow-up
      period.

PMID- 12495797
TI  - Behavioral naltrexone therapy: an integrated treatment for opiate dependence.
AB  - Treatment of opiate dependence with naltrexone has been limited by poor
      compliance. Behavioral Naltrexone Therapy (BNT) was developed to promote
      adherence to naltrexone and lifestyle changes supportive of abstinence, by
      incorporating components from empirically validated treatments, including Network
      Therapy with a significant other to monitor medication compliance, the Community
      Reinforcement Approach, and voucher incentives. An overview is presented of the
      BNT treatment manual. In an uncontrolled Stage I trial (N = 47), 19% completed
      the 6-month course of treatment. Retention was especially poor in the subsample
      of patients who were using methadone at baseline (N = 18; 39% completed 1 month,
      none completed 6 months), and more encouraging among heroin-dependent patients (N
      = 29; 65% completed 1 month, 31% completed 6 months). Thus, attrition continues
      to be a serious problem for naltrexone maintenance, although further efforts to
      develop interventions such as BNT are warranted.

PMID- 12495798
TI  - Naltrexone improves outcome of a controlled drinking program.
AB  - Naltrexone is widely used in therapeutic programs with abstinence as a goal.
      However, it has been used in only a few studies aimed at reducing alcohol
      consumption. The purpose of this study was to evaluate the efficacy of naltrexone
      as an adjunct in controlled drinking programs. This was an open randomized study
      of 12 weeks duration that compared two therapeutic strategies: use of naltrexone
      in a controlled drinking program (NTX+CD) and the controlled drinking program
      alone (CD), without NTX. Each group comprised 30 male patients with mild alcohol
      dependence. During treatment, there were no differences between groups in
      drinking behavior, though the NTX+CD group showed significantly less craving. In
      the 12-month follow-up period, the NTX+CD group showed significantly fewer
      drinking days and heavy drinking days and less craving than the CD group. The
      results of this study suggest a role for naltrexone in controlled drinking
      programs.

PMID- 12495800
TI  - Establishing the feasibility of performance measures for alcohol and other drugs.
AB  - The Washington Circle (a multiple-disciplinary group of providers, researchers,
      managed care representatives, and public policy representatives) examined three
      performance measures for alcohol and other drug (AOD) services. These measures,
      which were developed and applied to managed care organizations' administrative
      data for their commercial enrollees, are: (a) identification, the percent of
      adult enrollees with AOD diagnoses; (b) initiation, the percent of adults with an
      inpatient AOD admission or with an index outpatient visit for AOD abuse or
      dependence and any additional AOD services within 14 days of identification; and
      (c) engagement, the percent of adults diagnosed with AOD disorders that receives
      two additional AOD services within 30 days of the initiation of care. We conclude
      that using administrative databases to compare managed care organizations'
      performance is feasible, meaningful and informative. The article discusses issues
      in interpreting performance measures in several areas: organizational structure
      of alcohol and other drug services, information available for measurement, and
      computational issues.

PMID- 12495799
TI  - Is the FTND a measure of physical as well as psychological tobacco dependence?
AB  - The Fagerstrom Test for Nicotine Dependence (FTND) has been developed to assess
      tobacco dependence from a physical perspective and to match treatments to
      individuals on the basis of the extent of the physical dependence. This study
      assessed the extent to which the FTND also measures psychological tobacco
      dependence. In three independently recruited samples of smokers, FTND scores,
      scores on indices of psychological dependence and smoking cessation were
      assessed. The results show that the indices of psychological dependence in all
      three samples explained about 20% of the variance in FTND scores. Furthermore,
      the FTND and the indices of psychological dependence both predicted quitting
      activity prospectively with two quitting measures in all three samples. Lastly,
      when the FTND and the indices of psychological dependence were combined in one
      model, the psychological dependence measures predicted quitting activity more
      consistently than the FTND, although the overlap between the two measures of
      dependence was small.

PMID- 12495801
TI  - Participation and retention in drug abuse treatment services research.
AB  - We examined potential bias in treatment effectiveness research by studying client
      characteristics associated with initial participation and subsequent retention in
      research assessments among clients in substance abuse treatment receiving case
      management. Six hundred thirty-four residential and 429 outpatient clients were
      invited to participate. Participants were randomly assigned to one of four
      conditions. Logistic regression examined the relation between client
      characteristics and initial participation and retention in follow-up assessments.
      Females and clients with significant others were more likely to participate and
      remain in the study. Older persons and criminal justice-referred clients were
      less likely to participate. Older clients and urban outpatient clients were more
      likely, and criminal justice-referred clients were less likely, to be retained.
      Two case management conditions were associated with decreased retention. Client
      characteristics are important factors in participation and retention in treatment
      services research. Further, client characteristics may bias estimates of
      effectiveness generally, or for specific populations.

PMID- 12495803
TI  - Sensitivity to acute methadone dose changes in maintenance patients.
AB  - This study assessed whether methadone patients can identify acute dose changes in
      their maintenance dose, and explored the relationships between self-reported drug
      effects and real or perceived dose changes. Four times each week patients (N =
      10) unpredictably received either 80%, 90%, 100%, 110% or 120% of their usual
      daily dose (50-100 mg). Approximately 24 hr later they indicated which dose they
      had received on the previous day, and rated the previous day's dose in terms of
      good effects, bad effects, and change in medication taste. Correct estimation of
      the doses received was always at the levels expected by chance alone.
      Furthermore, this sample of patients could not detect dose-related changes in
      medication taste. However, self-reports of good effects were significantly higher
      when patients believed that they had received a dose increment, and ratings of
      bad effects were higher when patients believed that they had received a dose
      decrement.

PMID- 12495802
TI  - Gender differences in detoxification: predictors of completion and re-admission.
AB  - This study examined the medical records of 2595 consecutive admissions over a 3
      year period to an inpatient mixed-gender, hospital-based alcohol and drug
      detoxification unit. Women reported a significantly different pattern of primary
      drug use, a younger age, a different pattern of referral sources, and higher
      rates of parenting status and unemployment. In addition, females were
      administered prescription medication and medical evaluation tests at a
      significantly higher rate than males. Multiple regression analyses demonstrated
      that an opiate as a primary drug of choice was a significant risk factor for
      dropout. Risk factors for re-admission to inpatient detoxification included:
      alcohol as a primary drug of choice, residential instability, multiple drug use,
      single marital status, unemployment, an older age (> 37 years), and treatment
      dropout at Time 1 in the study. For both the final prediction models, gender was
      not a significant factor. The treatment implications of these findings are
      discussed.

PMID- 12495804
TI  - Buprenorphine treatment of opium-dependent outpatients seeking treatment in Iran.
AB  - The goal of this study was to evaluate the efficacy of 1-, 3-, and 8-mg per day
      doses of buprenorphine in the maintenance treatment of opium-dependent patients
      over a 6-month treatment period. Participants were 513 opium-dependent
      individuals who were seeking treatment in an urban outpatient clinic, offering a
      1-hr weekly individual counseling session. Overall, 305 patients (59.5%)
      completed the 6-month study. Completion rates by dosage group were 33.9% for the
      1-mg dose group, 64.3% for the 3-mg dose group, and 80.1% for the 8-mg dose group
      each significantly different from the other two groups. The results support the
      efficacy and safety of buprenorphine for outpatient treatment of opium dependence
      and seem to indicate that the highest dose (8 mg) of buprenorphine was the best
      of the three doses for Iranian opium-dependent patients to increase their
      retention in treatment.

PMID- 12495805
TI  - Psychometric properties of the Substance Abuse Subtle Screening Inventory-3.
AB  - The psychometric properties of the Substance Abuse Subtle Screening Inventory-3
      (SASSI-3) were analyzed using a sample of 254 college students. Internal
      consistency coefficients were calculated for the total scale and its subscales,
      with the face-valid subscales yielding the highest coefficients. The ability of
      the SASSI-3 to identify students with a current alcohol dependence disorder (as
      measured by the Composite International Diagnostic Interview - Substance Abuse
      Module, DSM-IV) was also evaluated. The total scale was found to offer only a
      very limited degree of clinical utility (sensitivity =.65). The scale's
      sensitivity was significantly enhanced when the cutting score for one of its
      subscales (the Face-Valid Alcohol [FVA] subscale) was optimized in the present
      sample (new sensitivity level =.89), but even with that change, the performance
      of the overall scale was matched by that of the FVA subscale alone. These results
      raise questions about the usefulness of the subtle items of the SASSI-3 in
      identifying alcohol dependence in a college population.

PMID- 12495807
TI  - Psychopathology influences treatment retention among drug-dependent women.
AB  - Three subgroups of drug dependent women (N = 78) were identified through cluster
      analysis on MCMI-II scores. Group 1 (26%) presented a relatively benign clinical
      picture. In contrast, Group 2 (37%) evidenced severe addiction, psychiatric (Axis
      I), and personality (Axis II) problems. Group 3 (37%) was characterized by fewer
      Axis I problems, prominent addiction and externalizing (Cluster B) personality
      deficits. Group membership was significantly associated with retention in a
      gender-specific day treatment program. Group 2 experienced rapid attrition, with
      only 36% completing treatment, compared to 57% for Group 1 and 76% for Group 3.
      Results indicate that drug-dependent women with externalizing psychopathology can
      be retained in treatment when environmental barriers are removed and an adequate
      "holding environment" is maintained. However, women with severe psychiatric
      problems, unstable mood, and interpersonal deficits are less likely to complete
      treatment. Early identification of women at risk for drop-out affords an
      opportunity to intervene to prevent its occurrence.

PMID- 12495806
TI  - Optimizing smoking cessation outcomes among the methadone maintained.
AB  - Several studies have shown high levels of interest in smoking cessation among
      methadone maintained heroin users, yet little is known about how to intervene
      most effectively with this population. The present study examined data from a
      large controlled trial of behavioral therapy in combination with nicotine
      replacement to find predictors of smoking cessation among the methadone
      maintained. Logistic regression analyses showed that less nicotine dependence, as
      measured by the Fagerstrom Test of Nicotine Dependence, and greater age were
      associated with higher rates of tobacco cessation. Greater opiate use, fewer
      nicotine patches used, and any tobacco smoking during weeks 2 and 3 of the
      intervention significantly negatively predicted smoking cessation outcomes.

PMID- 12495808
TI  - Improved health and self-esteem among patients with AIDS in a therapeutic
      community nursing program.
AB  - This study followed up 41 clients (26 males and 15 females) admitted into a
      modified therapeutic community (TC) nursing home for substance abusing clients
      with AIDS at 3 points in time (admission, 8 months into treatment, and after
      completing residential treatment, 16-18 months post baseline) using the Tennessee
      Self-Concept Scale and other biological and social indicators, such as CD-4 cell
      count, body weight, and number of close friends. Analyses of repeated measures
      found significant linear increases on total self-esteem, CD-4 cell count, and
      body weight biological indicators, and number of close friends social indicator.
      Discussion focused on the pertinence of the TC nursing home treatment on clients'
      internalized behavior self-concept change, as well as positive physical and
      social change indicators.

PMID- 12495810
TI  - Substrate specificity and kinetics for VP14, a carotenoid cleavage dioxygenase in
      the ABA biosynthetic pathway.
AB  - The plant growth regulator, abscisic acid (ABA), is synthesized via the oxidative
      cleavage of an epoxy-carotenoid. Specifically, a double bond is cleaved by
      molecular oxygen and an aldehyde is formed at the site of cleavage in both
      products. The Vp14 gene from maize encodes an oxidative cleavage enzyme for ABA
      biosynthesis and the recombinant VP14 protein catalyzes the cleavage reaction in
      vitro. The enzyme has a strict requirement for a 9-cis double bond adjacent to
      the site of cleavage (the 11-12 bond), but shows some plasticity in other
      features of carotenoids that are cleaved. A kinetic analysis with the 9-cis
      isomer of five carotenoids displays several substrate activity relationships. One
      of the carotenoids was not readily cleaved, but inhibited the cleavage of another
      substrate in mixed assays. Of the remaining four carotenoids used in this study,
      three of the substrates have similar V(max) values. The V(max) for the cleavage
      of one carotenoid substrate was significantly higher. Molecular modeling and
      several three-dimensional quantitative substrate-activity relationship programs
      were used to analyze these results. In addition to a 9-cis double bond, the
      presence and orientation of the ring hydroxyl affects substrate binding or the
      subsequent cleavage. Additional variations that affect substrate cleavage are
      proposed.

PMID- 12495809
TI  - Oxidative stress, NO* and smooth muscle cell extracellular superoxide dismutase
      expression.
AB  - Oxygen free radicals apparently play important roles in diseases of the blood
      vessel wall and increased secretion of superoxide radicals occurs in many
      situations. The vascular wall contains large amounts of extracellular superoxide
      dismutase (EC-SOD). The synthesis of the enzyme by the smooth muscle cells (SMC)
      is modulated by cytokines, growth factors, and vasoactive factors. Here we
      studied the effects of oxidants (pyrogallol, xanthine oxidase, Cu and Fe),
      antioxidants (SOD, catalase, and ascorbate), glutathione modulation (n
      acetylcysteine and buthionine sulfoximine) and nitric oxide on EC-SOD expression
      by human vascular SMCs. Generally, the responses in EC-SOD synthesis were small,
      and no changes were noted in mRNA levels. High concentrations of some of the
      agents caused reductions in EC-SOD synthesis, mostly concomitantly with toxic
      effects on the cells. Cell cultures are normally ascorbate deficient, and
      addition of ascorbate to approach physiological levels doubled the EC-SOD
      content. Iron ions up-regulated EC-SOD synthesis but also blocked the secretion
      of the enzyme. Only down-regulation was found by NO*-releasing compounds.In
      conclusion, there is limited response to oxidant stress of EC-SOD synthesis by
      SMCs on a cell-autonomous level. The synthesis appears mainly regulated by
      factors coordinating concerted tissue responses.

PMID- 12495811
TI  - Ligand binding subsequent to CO photolysis of methionine-modified cytochrome c.
AB  - In this report the kinetics of CO recombination to ferrocytochrome c in which
      Met80 has been oxidized to a sulfoxide are examined. Transient optical difference
      spectra suggest that the species formed immediately after photolysis contains a
      five-coordinate high spin heme. Single wavelength transient absorption data show
      triphasic kinetics with rate constants of (2.1+/-0.08)x10(4), (2.0+/-0.01)x10(3),
      and 57+/-0.01 s(-1). The data suggest a model for ligand recombination in which
      the methionine sulfoxide and CO compete for binding to the five-coordinate heme
      with rate constants of (2.1+/-0.08)x10(4) and (2.0+/-0.01)x10(3) s(-1),
      respectively. Carbon monoxide then binds to the population of cytochrome c
      containing the methionine sulfoxide with a rate constant of 57 s(-1). In
      addition, the slower than expected rate of methionine sulfoxide recombination
      (much smaller rate constant than expected for a ligand restricted to the distal
      heme pocket) is attributed to hydrogen bonding between the unbound methionine
      sulfoxide and Tyr(68).

PMID- 12495812
TI  - Cloning, heterologous expression, and characterization of recombinant class II
      cytochromes c from Rhodopseudomonas palustris.
AB  - The cytochrome (cyt) c', cyt c(556), and cyt c(2) genes from Rhodopseudomonas
      palustris have been cloned; recombinant cyt c' and cyt c(556) have been
      expressed, purified, and characterized. Unlike mitochondrial cyt c, these two
      proteins are structurally similar to cyt b(562), in which the heme is embedded in
      a four-helix bundle. The hemes in both recombinant proteins form covalent
      thioether links to two Cys residues. UV/vis spectra of the Fe(II) and Fe(III)
      states of the recombinant cyts are identical with those of the corresponding
      native proteins. Equilibrium unfolding measurements in guanidine hydrochloride
      solutions confirm that native Fe(II)-cyt c(556) is more stable than the
      corresponding state of Fe(III)-cyt c(556) (DeltaDeltaG(f)(o) =22 kJ/mol).

PMID- 12495813
TI  - Physiologic pH changes modulate calcium ion dependence of brain nitric oxide
      synthase in Carassius auratus.
AB  - Species of the fish genus Carassius survive prolonged anoxia. Nitric oxide (NO)
      regulates cerebral blood flow in these fish during normoxic conditions whereas
      adenosine is the main vasoregulating molecule during anoxia. We investigated the
      calcium ion dependence of Carassius auratus brain NO synthase (NOS) as a function
      of pH. The physiological pH decrease from 7.2 to 6.8, which takes place during
      anoxia, greatly decreases NOS activity. This strong pH dependence is mainly due
      to variation of the calcium sensitivity of the enzyme. The EC(50) is 0.15 microM
      at pH 7.2 and 2.1 microM at pH 6.8 for the soluble enzyme. The particulate enzyme
      is also dependent on pH variations. The reduced sensitivity to calcium ions at
      acidic pH decreases both NO and H(2)O(2) production, saving the cells by
      suppression of the formation of potentially toxic nitrogen and oxygen species.
      Modulation of NOS activity by variation of its calcium affinity within the range
      of physiological pH constitutes an important and rapid mechanism to control the
      formation of NO and H(2)O(2) during normoxia-anoxia and anoxia-normoxia
      transitions.

PMID- 12495814
TI  - Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive
      quinone generation in neuroblastoma cells.
AB  - Neurotoxic properties of L-dopa and dopamine (DA)-related compounds were assessed
      in human neuroblastoma SH-SY5Y cells with reference to their structural
      relationship. L-Dopa and its metabolites containing two free hydroxyl residues on
      their benzene ring showed toxicity in the cell, which was prevented by superoxide
      dismutase (SOD) and reduced glutathione (GSH), but not by catalase. Furthermore,
      a synthetic derivative of DA, 3-hydroxy-4-methoxyphenethylamine (HMPE) containing
      methoxy residue at position 4 in the benzene ring, exerted partial cytotoxicity,
      which was not prevented by SOD, GSH or catalase. However, the metabolites
      containing methoxy residue at position 3 failed to show a toxic effect in the SH
      SY5Y cells. Moreover, DA induced apoptotic cell death, which was observed by
      nuclear and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) staining and measurement of caspase-3 activity; this compound up
      regulated apoptotic factor p53 while down-regulating anti-apoptotic factor Bcl-2.
      In the cell-free in vitro electron spin resonance (ESR) spectrometry, DA
      possessing two hydroxyl groups showed generation of DA-semiquinone radicals,
      which were markedly prevented by addition of SOD or GSH but not by catalase. On
      the other hand, methylation of one of the hydroxyl residues on the benzene ring
      of DA converted DA to an unoxidizable compound (3-MT or HMPE), and caused it to
      lose the property to produce semiquinone radicals. It has been previously
      reported that SOD acting as a superoxide:semiquinone oxidoreductase prevents
      quinone formation, and that reduced GSH through forming a complex with DA-quinone
      prevents quinone binding to the thiol group of the intact protein. Therefore, the
      present results suggest that DA and its metabolites containing two hydroxyl
      residues exert cytotoxicity mainly due to generation of highly reactive quinones.

PMID- 12495815
TI  - Evidence for various calcium sites in human hair shaft revealed by sub-micrometer
      X-ray fluorescence.
AB  - New information about calcium status in human scalp hair shaft, deduced from X
      ray micro-fluorescence imaging, including its distribution over the hair section,
      the existence of one or several binding-types and its variation between people,
      is presented. The existence of two different calcium types is inferred. The first
      one corresponds to atoms (or ions) easily removable by hydrochloric acid, located
      in the cortex (granules), in the cuticle zone and also in the core of the
      medulla, which can reasonably be identified as calcium soaps. The second type
      consists of non-easily removable calcium atoms (or ions) that are located in the
      medulla wall, probably also in the cuticle, and rather uniformly in the cortex;
      these calcium atoms may be involved in Ca(2+)-binding proteins, and their
      concentration is fairly constant from one subject to another. In addition to its
      nonuniform distribution across the hair section, the second striking feature of
      the first type calcium content is its high variability from one subject to
      another, by up to a factor 10. We expect this information to be useful for
      analyzing in more detail the relationship between hair calcium and environmental
      and medical factors.

PMID- 12495816
TI  - Structural changes in DNA mediated by cationic lipids alter in vitro
      transcriptional activity at low charge ratios.
AB  - Lipid/DNA complexes or Lipoplexes have been characterized by various biochemical
      and biophysical methods to understand the physical basis of transfection. Here we
      have addressed the effect of cationic liposomes, 1,2-dioleoyl-3-trimethylammonium
      propane (DOTAP), on transcription of DNA templates in vitro. Transcriptional
      activity of DNA-dependent RNA polymerase at DNA templates complexed with the
      cationic lipid varied as a function of charge ratio of lipid/DNA. At low charge
      ratios of 0.3:1 lipid/DNA and up to 1:1, we observed stimulation in
      transcription, while at higher charge ratios of lipid/DNA 3:1, complete
      inhibition in the activity occurred. Cetyl tri-methyl ammonium bromide (CTAB), a
      cationic detergent, and polyethylenimine (PEI), a cationic polymer, also bring
      about similar changes although to a lesser extent. The stimulation in
      transcription motivated us to probe into the molecular nature of the lipid/DNA
      interactions by absorbance spectroscopy and circular dichroism (CD). Upon
      interaction with lipids, hyperchromicity and susceptibility to micrococcal
      nuclease has increased, which suggests that the DNA was partially denatured. On
      complexation with the cationic lipid (DOTAP), the magnitude of the positive band
      in CD spectra decreased, accompanied with a red shift, as a function of charge
      ratio. Results from spectroscopic and enzyme assays suggest that at low charge
      ratios DNA may be partially unwound.

PMID- 12495817
TI  - Aluminum detoxification in Pseudomonas fluorescens is mediated by oxalate and
      phosphatidylethanolamine.
AB  - 13C NMR studies with aluminum (Al)-stressed Pseudomonas fluorescens revealed that
      the trivalent metal was secreted in association with oxalate and
      phosphatidylethanolamine (PE). These moieties were observed in the insoluble
      pellet obtained upon incubation of these resting cells in the presence of either
      Al-citrate or citrate. This extrusion process was concomitant with the
      utilization of either of these tricarboxylic acids as a substrate. While only
      minimal amounts of Al were secreted in the presence of such carbon source as
      glucose, succinate or oxaloacetate, oxalate did permit the efflux of Al. Neither
      alpha-ketoglutarate nor ethylenediaminetetraacetic acid (EDTA) was effective in
      dislocating Al from the cells. The elimination of Al from the cells did not
      appear to be affected by p-dinitrophenol (DNP) or dicyclohexylcarbodiimide (DCCD)
      or azide, but was sensitive to temperature, pH and cerulenin, an inhibitor of
      lipid synthesis. Thus, it appears that P. fluorescens detoxifies Al via its
      extrusion in association with oxalate and PE in a process that apparently does
      not necessitate the direct utilization of energy.

PMID- 12495818
TI  - The export of metabolites from mitochondria and anaplerosis in insulin secretion.
AB  - Combinations of insulin secretagogue-derived metabolites were added to microgram
      amounts of mitochondria obtained from rat and mouse pancreatic islets and the INS
      1 cell line, and the export of citric acid cycle intermediates was surveyed to
      study anaplerosis in insulin secretion. Cellular levels of metabolites were also
      measured. In mitochondria from all three tissues, malate production was the most
      responsive to various substrates. The export of citrate and isocitrate in the
      presence of pyruvate and most other substrates was small and their levels in
      intact cells did not change with any secretagogue, except in INS-1 cells where
      citrate increased slightly. Changes in alpha-ketoglutarate and glutamate export
      from mitochondria and levels in intact cells indicate that glutamate can be
      consumed as a fuel secretagogue, but it is not likely produced as a messenger in
      insulin secretion. The citrate level may not need to increase in order to provide
      increased malonyl-CoA for signaling insulin secretion. Unlike some cells, insulin
      cells probably obtain cytosolic NADPH equivalents by exporting them from
      mitochondria to the cytosol via a pyruvate malate shuttle or an isocitrate
      shuttle. Only fuels that can enhance anaplerosis via pyruvate or alpha
      ketoglutarate can be insulin secretagogues.

PMID- 12495819
TI  - Characterisation of the gptA gene, encoding UDP N-acetylglucosamine: dolichol
      phosphate N-acetylglucosaminylphosphoryl transferase, from the filamentous
      fungus, Aspergillus niger.
AB  - The production of asparagine (N)-linked oligosaccharides is of vital importance
      in the formation of glycosylated proteins in eukaryotes and is mediated by the
      dolichol pathway. As part of studies to allow manipulation of this pathway, the
      gene coding for the production of the enzyme UDP N-acetylglucosamine: dolichol
      phosphate N-acetylglucosaminylphosphoryl transferase (GPT), catalysing the first
      step in the assembly of dolichol-linked oligosaccharides, was cloned from the
      filamentous fungus Aspergillus niger. Degenerate-PCR was used to amplify a 470-bp
      fragment of the gene, which was labelled as a probe to obtain a full-length clone
      from a genomic library of A. niger. This contained a 1557-bp open reading frame
      encoding a highly hydrophobic protein of 468 amino acids with a predicted
      molecular weight of 51.4 kDa. The gene contained two intron sequences and
      putative dolichol recognition sites (PDRSs) were present in the deduced amino
      acid sequence. Comparison with other eukaryotic GPTs revealed the A. niger GPT to
      share 45-47% identity with yeasts (Saccharomyces cerevisiae and
      Schizosaccharomyces pombe) and 41-42% identity with mammals (mouse, hamster,
      human). Nested-PCR of a cDNA library was used to confirm the position of an
      intron. A complete cDNA clone of A. niger gpt was obtained by employing a
      recombinant PCR approach. This was used to rescue a conditional lethal mutant of
      S. cerevisiae carrying a dysfunctional gpt gene by heterologous expression,
      confirming that the gpt genes from A. niger and S. cerevisiae are functionally
      equivalent.

PMID- 12495820
TI  - A comparative analysis of structure and spatial distribution of decorin in human
      leiomyoma and normal myometrium.
AB  - Leiomyoma is a benign smooth muscle tumor of the uterus that affects many women
      in active reproductive life. It is composed by bundles of smooth muscle cells
      surrounded by extracellular matrix. We have recently shown that the glycosylation
      of extracellular matrix proteoglycans is modified in leiomyoma: increased amounts
      of galactosaminoglycans with structural modifications are present. The data here
      presented show that decorin is present in both normal myometrium and leiomyoma
      but tumoral decorin is glycosylated with longer galactosaminoglycan side chains.
      Furthermore, these chains contain a higher ratio D-glucuronate/L-iduronate, as
      compared to normal tissue. To determine if these changes in proteoglycan
      glycosylation correlates with modifications in the extracellular matrix
      organization, we compared the general structural architecture of leiomyoma to
      normal myometrium. By histochemical and immunofluorescence methods, we found a
      reorganization of muscle fibers and extracellular matrix, with changes in the
      distribution of glycoproteins, proteoglycans, and collagen. Thin reticular
      fibers, possibly composed by types I and III collagen, were replaced by thick
      fibers, possibly richer in type I collagen. Type I collagen colocalized with
      decorin both in leiomyoma and normal myometrium, in contrast to type IV collagen
      that did not. The relative amount of decorin was increased and the distribution
      of decorin and collagen was totally modified in the tumor, as compared to the
      normal myometrium. These findings reveal that not only decorin structure is
      modified in leiomyoma but also the tissue architecture changed, especially
      concerning extracellular matrix.

PMID- 12495821
TI  - [Postural strategies and falls in elderly and in parkinsonism].
AB  - OBJECTIVE: To use a posture analysis to show the evolution of postural pattern
      connected with falls. MATERIAL AND METHOD: It is a prospective study on two
      groups of 16 persons of more than 60 years. A group concerns 16 small disability
      off drug parkinsonian patients, a group concerns 16 healthy witnesses. All the
      persons benefited from a posture recording by means of a force platform and were
      followed during 1 year. RESULTS: Data analysis underlines three groups of persons
      corresponding to three postural patterns, independently of the presence of
      Parkinson disease. A group (n = 18) did not contain fallers, the second (n = 10 )
      contained 20% of fallers, the third (n = 4) contained 100% of fallers.
      Differences between the groups were identified on 16 posturographic parameters.
      DISCUSSION: A group has a good functional value and one does not record any fall.
      Its characteristics, which correspond to a category of persons who compensate
      well for the phenomena of ageing, are found in the literature. A group has an
      intermediate functional value and regrets 20% of fallers. Kinetic profile reveals
      a tendency to the stiffness of the posture. This group is going to operate rather
      ankle strategies. A group has an inferior functional value and regrets 100% of
      fallers. Kinetic profile seems disrupted and not to be able to adapt itself in a
      satisfactory way to the situation otherwise than by stereotypical reactions. This
      group is going to operate systematically much less stabilizing hip strategies.
      CONCLUSION: A close determinism between physiological neuromotor ageing and
      Parkinson disease does exist. We showed with a prospective follow-up, the arisen
      of fall and showed the evolution of postural patterns related to fall. It appears
      as well that evolution mainly follows three stages leading from a small risk of
      fall gait pattern to a major risk of fall gait pattern.

PMID- 12495822
TI  - [Effectiveness of falls prevention strategies for elderly subjects who live in
      the community with performance assessment of physical activities (before-after)].
AB  - OBJECTIVES: The development of falls prevention strategies is an essential health
      concern in elderly people. However, a global consensus does not exist for elderly
      subjects who live independently in the community. The aim of the study was to
      evaluate the benefit of an exercises program. MATERIALS AND METHODS: A control
      group (153 subjects) and an "Intervention" group (150 subjects) were tested
      before and after a 1-year prospective study. The "Intervention" group performed
      ten training sessions of physical activity, based on balance, muscular activity
      and coordination. We compared the incidence of falls, and the performances in
      several tests between the two groups. RESULTS: The clinical features were similar
      between the two groups: mean age 71 years, 83% of females, subjects who were
      independent for activities of daily living. However, all subjects presented risk
      for factors for falls: 38% were not able to maintain the unipodal position more
      than five seconds, 29% had already fallen during the previous year. For the
      "Intervention" group, the comparison of the performances before and after the
      physical activity program showed significant increases (p < 0.001) for all the
      tests, and specifically for the unipodal position and for the exercises performed
      with eyes closed. After one year follow-up, the incidence rate of falls was lower
      in the "Intervention" group compared with the control group, but the difference
      was not significant (p = 0.32). However, falls occurred significantly latter in
      the "Intervention" group (p = 0.02). CONCLUSION: Ten training sessions of
      physical activity allowed to improve the performance of elderly people in several
      tests. This result suggests that a fall prevention program based on collective
      and regular exercises, may be efficient for elderly subjects who still have an
      active and independent way of live.

PMID- 12495823
TI  - [Clinical factors associate with shoulder subluxation in stroke patients].
AB  - OBJECTIVE: This study explores whether shoulder subluxation after stroke is
      related to age, hemiplegic side motor impairment, spasticity, sensory deficit,
      depression, unilateral neglect and length of stay in acute ward. METHOD: This
      prospective study included 57 patients with hemiplegia. The shoulder subluxation
      was systematically detected by radiography and quantified according to de Bats
      score. The complete clinical assessment of the upper limb on day 15 analyzed
      motricity (motricity index), spasticity of shoulder adductors and biceps
      (Ashworth), sensory deficit, unilateral neglect and depression (MADRS). Age, side
      of hemiplegia and the aetiology were also noted. We researched relations between
      shoulder subluxation and these clinical factors. Means were compared using Mann
      Whitney and chi(2) tests. Coefficients of correlation were estimated between two
      quantitative variables. A multiple regression analysis was also conducted
      including all significant parameters, the dependent variable being the shoulder
      subluxation. RESULTS: Shoulder subluxation was observed in 32% of hemiplegic
      patients. After multiple regression analysis, the main clinical factors related
      to subluxation were motor (p < 0.0001), spasticity of shoulder adductors (p =
      0.028) and age (p = 0.036). Statistically, the risk of subluxation was divided by
      1.62 (1.07, 2.43) for every five years age growth and by two (1.33, 2.94) when
      the motricity index went up by ten points. CONCLUSION: This study shows that the
      age could play an independent part. The loss of elasticity of the periarticular
      tissues when ageing could have a protective role.

PMID- 12495824
TI  - [Evaluation of pendulum testing of spasticity].
AB  - OBJECTIVES: To identify valid measurements of spasticity derived from the
      pendulum test of the leg in a representative population of spastic patients.
      MATERIAL AND METHODS: Pendulum testing was performed in 15 spastic and 10 matched
      healthy subjects. The reflex-mediated torque evoked in quadriceps femoris, as
      well as muscle mechanical parameters (viscosity and elasticity), were calculated
      using mathematical modelling. Correlation with the two main measures derived from
      the pendulum test reported in the literature (the Relaxation Index and the area
      under the curve) was calculated in order to select the most valid. RESULTS,
      DISCUSSION: Among mechanical parameters, only viscosity was found to be
      significantly higher in the spastic group. As expected, the computed integral of
      the reflex-mediated torque was found to be larger in spastics than in healthy
      subjects. A significant non-linear (logarithmic) correlation was found between
      the clinically-assessed muscle spasticity (Ashworth grading) and the computed
      reflex-mediated torque, emphasising the non-linear behaviour of this scale. Among
      measurements derived from the pendulum test which are proposed in the literature
      for routine estimation of spasticity, the Relaxation Index exhibited an
      unsuitable U-shaped pattern of variation with increasing reflex-mediated torque.
      On the opposite, the area under the curve revealed a linear regression, which is
      more convenient for routine estimation of spasticity. CONCLUSION: The pendulum
      test of the leg is a simple technique for the assessment of spastic hypertonia.
      However, the measurement generally used in the literature (the Relaxation Index)
      exhibits serious limitations, and would benefit to be replaced by more valid
      measures, such as the area under the goniometric curve, especially for the
      assessment of therapeutics.

PMID- 12495825
TI  - [Heterotopic ossification and brain injury].
AB  - OBJECTIVES: The aim of the study was to evaluate the incidence and the risk
      factors of heterotopic ossifications in patients with severe traumatic brain
      injury. MATERIAL AND METHODS: This retrospective study was conducted in a sample
      of 86 patients during a two years period. These patients were receiving care in
      an acute rehabilitation setting designed for traumatic brain injury patients
      emerging from coma. The statistical analysis used chi(2) and Fisher tests.
      RESULTS, DISCUSSION: Forty-nine heterotopic ossifications were observed in 24
      patients (incidence 28.57%, 2.04/patient). Most of them were localised at the
      level of the hip, of the elbow and of the knee. No significant relation was found
      between heterotopic ossification and sex, age, clinical severity, motor
      impairment, spasticity or autonomic dysreflexia. On the contrary, associated limb
      fractures, specially when requiring a surgical treatment, were found to be
      correlated to a greater incidence of heterotopic ossification. CONCLUSION: Some
      of the risk factors observed in the present study were in accordance with those
      previously described in the literature. This work shows the difficult place of
      the initial care of patients with severe traumatic brain injury specially during
      there stay in intensive care units.

PMID- 12495826
TI  - Material and behavioral factors in the explanation of educational differences in
      incidence of acute myocardial infarction: the Globe study.
AB  - PURPOSE: To quantify the contribution of material and behavioral factors to
      educational differences in the incidence of acute myocardial infarction (AMI),
      taking into account their interrelationship. METHODS: Self-reported information
      about educational level, behavioral factors (alcohol, smoking, physical
      inactivity, and obesity), and material factors (housing conditions, crowding,
      employment status, financial problems, and an income proxy) was obtained from 45
      to 74 year old responders to the baseline measurement of the Dutch prospective
      GLOBE-study in 1991 (n = 9872). Incidence of AMI in study participants was
      determined by hospital admissions due to AMI between 1991 and 1998. RESULTS: The
      increased hazard ratio of AMI in the lowest compared to the highest educational
      group [hazard ratio (HR) = 1.85, 95% confidence interval (CI): 1.19; 2.88]
      decreased by 60% after adjustment for all four behavioral factors. Similarly,
      adjustment for housing conditions, employment status and the income proxy reduced
      the hazard ratio by 76%. Thirty-six percent of the contribution of behavioral
      factors to educational differences in AMI in the lowest compared to the highest
      educational group was the result of more often living in worse material
      circumstances in the first group. CONCLUSIONS: Material factors contribute more
      to educational differences in incidence of AMI than behavioral factors. Improving
      material circumstances in lower educational groups may form an important strategy
      in the reduction of inequalities in AMI, partly because of its influence on
      unhealthy behavior.

PMID- 12495827
TI  - The relationship of physical activity and body weight with all-cause mortality:
      results from the Puerto Rico Heart Health Program.
AB  - PURPOSE: To study the relationship of physical activity and obesity with all
      cause mortality in Puerto Rican Men. METHODS: The Puerto Rico Heart Health
      Program collected physical activity and anthropometric measurements in 9,824 men
      between 1962 and 1965. After excluding those with known coronary heart disease at
      baseline, and those who died within the first three years of the study we
      analyzed the data for the relationship between physical activity and overweight
      status to all-cause mortality in 9,136 men. We stratified our participants by
      quartiles of physical activity. Participants were classified into four categories
      of body weight: underweight (BMI < 18.5), healthy weight (BMI =18.5-24.9),
      overweight (BMI = 25-29.9), and obese (BMI = 30+). RESULTS: After adjusting for
      age, education, smoking status, hypertension status, hypercholesterolemic status,
      urban/rural residence, and overweight status, physical activity was independently
      related to all-cause mortality. All-cause mortality was lower in those in
      quartile 2 (OR = 0.68, CI = 0.58-0.79) than quartile 1 (reference, sedentary
      group). Mortality among those in quartile 3 and 4 (0.63, CI = 0.54-0.75; and
      0.55, CI = 0.46-0.65, respectively) were also significantly lower than those
      observed in quartile 1, but not significantly lower than those observed in
      quartile 2. Furthermore, within every category of body weight, those who were
      most active had significantly lower odds ratio of all-cause mortality.
      CONCLUSION: Our findings support the current recommendation that some physical
      activity is better than none, in protecting against all-cause mortality. The
      benefits of an active lifestyle are independent of body weight and that
      overweight and obese Puerto Rican men who are physically active experienced
      significant reductions in all-cause mortality compared with their sedentary
      counterparts.

PMID- 12495828
TI  - Time-course of adiposity and fasting insulin from childhood to young adulthood in
      offspring of parents with coronary artery disease: the Bogalusa Heart Study.
AB  - PURPOSE: Obesity and the attendant insulin resistance/hyperinsulinemia related to
      coronary artery disease (CAD) morbidity and mortality are well documented.
      However, information is lacking on the time-course relation of adiposity and
      fasting insulin from childhood to young adulthood in offspring of parents with
      CAD, a surrogate measure of future risk. METHODS: Longitudinal analysis was
      performed on data collected from the Bogalusa Heart Study cohort with (n = 271)
      and without (n = 805) a parental history of CAD followed since childhood by
      repeated surveys from 1973 to 1991. RESULTS: Lowess smoothing and multivariate
      analyses using Generalized Estimating Equations revealed that body mass index,
      triceps, and subscapular skinfolds were consistently higher from childhood to
      adulthood in offspring of parents with CAD history. Insulin levels during
      childhood and adolescence were lower in the offspring with affected parents. On
      the other hand, higher levels of fasting insulin from offspring were associated
      with positive parental history of CAD after age 20 and this association remained
      significant even after adjusting for body mass index. There was no significant
      interaction with race or sex in these relationships. CONCLUSION: These results
      indicate that the offspring at high risk for CAD develop excess body fatness
      beginning in childhood and then later manifest hyperinsulinemia in young
      adulthood. These observations have important implications for prevention.

PMID- 12495829
TI  - Smoking, alcohol drinking and non-fatal coronary heart disease in Hong Kong
      Chinese.
AB  - PURPOSE: To examine whether smoking, alcohol drinking and other risk factors were
      associated with non-fatal coronary heart disease (CHD) in Hong Kong Chinese.
      METHODS: A case control study was carried out with 598 CHD hospital cases (431
      men, 167 women) and 1100 community controls (663 men, 437 women). Standardized
      questionnaires were used and blood lipids were measured using standard methods.
      RESULTS: Stepwise logistic regression models showed adjusted odds ratios (AOR) of
      3.36 [95% confidence interval (CI): 2.35 to 4.81] for smoking and 0.32 (95% CI:
      0.22 to 0.45) for alcohol drinking in men, and 6.50 (95% CI: 2.61 to 16.19) and
      0.15 (95% CI: 0.08 to 0.30), respectively, in women. The OR increased with
      decreasing levels of high-density lipoprotein cholesterol (HDL) and increasing
      levels of triglycerides. No patterns were observed for body mass index (BMI),
      total and low-density lipoprotein cholesterol (LDL). The protective effect of
      drinking was observed for different types of drinks and frequency of drinking,
      although few drank alcohol more than 3 days per week. CONCLUSIONS: Smoking was a
      strong risk factor and moderate alcohol drinking was a protective factor for CHD,
      and low HDL and high triglyceride levels were important risk factors in Hong Kong
      Chinese.

PMID- 12495830
TI  - Fine particulate air pollution and all-cause mortality within the Harvard Six
      Cities Study: variations in risk by period of exposure.
AB  - PURPOSE: We used Poisson regression methods to examine the relation between
      temporal changes in the levels of fine particulate air pollution (PM(2.5)) and
      the risk of mortality among participants of the Harvard Six Cities longitudinal
      study. METHODS: Our analyses were based on 1430 deaths that occurred between 1974
      and 1991 in a cohort that accumulated 105,714 person-years of follow-up. For each
      city, indices of PM(2.5) were derived using daily samples. Individual level data
      were collected on several risk factors including: smoking, education, body mass
      index (BMI), and occupational exposure to dusts. Time-dependent indices of
      PM(2.5) were created across 13 calendar periods (< 1979, 1979, 1980, em leader,
      1989, >/= 1990) to explore whether recent or chronic exposures were more
      important predictors of mortality. RESULTS: The relative risk (RR) of mortality
      calculated using Poisson regression based on average city-specific exposures that
      remained constant during follow-up was 1.31 [95% confidence interval (CI) = 1.12
      1.52] per 18.6 microg/m(3) of PM(2.5). This result was similar to the risk
      calculated using the Cox model (RR = 1.26, 95% CI = 1.08-1.46). The RR of
      mortality was attenuated when the Poisson regression model included a time
      dependent estimate of exposure (RR = 1.19, 95% CI = 1.04-1.36). There was little
      variation in RR across time-dependent indices of PM(2.5). CONCLUSIONS: The
      attenuated risk of mortality that was observed with a time-dependent index of
      PM(2.5) is due to the combined influence of city-specific variations in mortality
      rates and decreasing levels of air pollution that occurred during follow-up. The
      RR of mortality associated with PM(2.5) did not depend on when exposure occurred
      in relation to death, possibly because of little variation between the time
      dependent city-specific exposure indices.

PMID- 12495831
TI  - Systematic errors in middle-aged women's estimates of energy intake: comparing
      three self-report measures to total energy expenditure from doubly labeled water.
AB  - PURPOSE: To evaluate energy intake (EI) derived from a food frequency
      questionnaire (FFQ), seven-day dietary recall (7DDR), and seven 24-hour dietary
      recall interviews (24HR) for reporting errors associated with social desirability
      and social approval. METHODS: The FFQ and 7DDR were administered once before and
      once after a 14-day metabolic period during which total energy expenditure was
      determined using the doubly labeled water method (TEE(dlw)). Seven 24HR were
      conducted over the 14-day period. Data obtained from 80 healthy women (mean age =
      49.1 years) were fit to linear regression models in which the EI estimates were
      the dependent variables and estimates of social desirability and social approval
      traits, body mass index [weight (kg)/ height (m)(2)], and TEE(dlw) were fit as
      independent variables. RESULTS: indicated that in college-educated women there
      was an underestimate associated with social desirability on the FFQ (-42.24
      kcal/day/point on the social desirability scale; 95% CI:-75.48, -9.00). For
      college-educated women with an average social desirability score ( approximately
      17 points) this would equal an underestimate of 507 kcal/day compared to women
      with the minimum score (4 points). The 7DDR was associated with a differential
      effect of social approval when comparing by education; i.e., there was a
      difference of 36.35 kcal/day/point between the two groups (-14.69 in women with
      >/=college and 21.66 in women with <college) (95% CI: 10.25, 62.45). CONCLUSIONS:
      Social desirability and social approval distort energy intake estimates from
      structured questionnaires, in a manner that appears to vary by educational
      status. Results observed have important implications for subject recruitment,
      data collection, and for methods of detection and control of biases in
      epidemiologic studies.

PMID- 12495833
TI  - 'Mind the gap'.

PMID- 12495832
TI  - Electrolyte intake and nonpharmacologic blood pressure control.
AB  - PURPOSE: To characterize relationships between sodium and potassium intakes and
      blood pressure control. METHODS: We analyzed repeated 24-hour diet recalls and 24
      hour urine assays from 873 elderly participants with established hypertension in
      a 3-year clinical trial of lifestyle interventions. Pooled estimates of
      electrolyte intakes were developed using hierarchical measurement error models
      and related to nonpharmacologic blood pressure control. RESULTS: Relative
      decreases in sodium and increases in potassium intakes each had graded
      relationships with better blood pressure control. After adjustment for
      measurement error, a 100 mmol/24-hour decrease in sodium intake was associated
      with an odds ratio of 2.93 [95% confidence interval: 1.83, 4.64] for maintaining
      nonpharmacologic blood pressure control throughout follow-up. A 50 mmol/24-hour
      increase in potassium intake was associated with an odds ratio of 2.00 [1.12,
      3.55]. These relationships were independent of each other and of baseline levels
      of intakes. Blood pressure control was most strongly associated with sodium
      intake for participants with lower systolic blood pressures and longer duration
      of hypertension, and with potassium for those with elevated diastolic blood
      pressures. CONCLUSIONS: Sodium and potassium intakes exert independent graded
      influences on nonpharmacologic blood pressure control. Correlated measurement
      error may spuriously introduce a dependency among these relationships.

PMID- 12495834
TI  - Membranes and motors.
AB  - The 55(th) Harden Conference on the dynamics of membrane traffic convened on the
      25(th) August 2002 in the English Lake District. This meeting, which was
      organized by Bob Burgoyne and Viki Allan under the auspices of the Biochemical
      Society, comprised a highly enjoyable mixture of well-presented talks with
      uncommonly good weather. Presentations covered a broad range of topics relating
      to the dynamics of protein transport along both the exocytic and endocytic
      pathways of eukaryotic cells.

PMID- 12495835
TI  - New tricks for ubiquitin and friends.
AB  - The foothills of the Rocky Mountains provided a spectacular setting for the
      American Society for Cell Biology (ASCB) meeting entitled 'Non-traditional
      functions of ubiquitin and ubiquitin-like proteins', Colorado College, Colorado
      Springs, CO, USA, on 11-14 August, 2002. Organizers Linda Hicke and Cecile
      Pickart put together an excellent programme of talks covering functions of
      ubiquitin other than its well known role in proteasomal targeting. The
      increasingly diverse biological processes in which the ubiquitin-like proteins
      (UBLs) are involved, also featured. One of the aims of the meeting was to bring
      together researchers working directly with ubiquitin and UBLs, and also those who
      have found that their favourite molecule or process is somehow influenced by
      these small versatile tags. As a result, delegates were treated to a diverse and
      highly stimulating meeting.

PMID- 12495839
TI  - Live cell imaging: the 'green revolution' continues apace.

PMID- 12495840
TI  - Two blades of a sword: degradation coupled to deubiquitination.

PMID- 12495842
TI  - Intraflagellar transport and cilia-dependent diseases.
AB  - Intraflagellar transport involves the movement of large protein particles along
      ciliary microtubules and is required for the assembly and maintenance of
      eukaryotic cilia and flagella. Intraflagellar-transport defects in the mouse
      cause a range of diseases including polycystic kidney disease, retinal
      degeneration and the laterality abnormality situs inversus, highlighting the
      important role that motile, sensory and primary cilia play in vertebrates.

PMID- 12495843
TI  - Alzheimer disease gamma-secretase: a complex story of GxGD-type presenilin
      proteases.
AB  - Gamma-secretase is a pivotal enzymatic activity in Alzheimer disease that was
      hidden within a huge number of unrelated proteases. Only recently it has become
      clear that a protease complex containing presenilin, nicastrin, PEN-2 and
      probably APH-1 provides the long sought gamma-secretase activity. Presenilin
      itself appears to be a novel polytopic aspartyl protease of the GxGD type,
      whereas the other components might be required for substrate recognition, complex
      assembly, stability and targeting of the complex to its sites of action.

PMID- 12495844
TI  - Pathways and consequences: Hedgehog signaling in human disease.
AB  - Signaling pathways that play a fundamental role during development are turning
      out to underlie many disease states when misregulated. Here, we review some of
      the recent findings in the Hedgehog (Hh) pathway and the role it plays in
      different human diseases. We present a summary of the diseases that result from
      the inactivation or inappropriate activation of the Hh pathway. The human
      phenotypes generally fit the findings in model organisms and help to identify
      some potential targets for therapy.

PMID- 12495845
TI  - Mechanisms of enveloped RNA virus budding.
AB  - To spread infection, enveloped viruses must bud from infected host cells. Recent
      research indicates that HIV and other enveloped RNA viruses bud by appropriating
      the cellular machinery that is normally used to create vesicles that bud into
      late endosomal compartments called multivesicular bodies. This new model of virus
      budding has many potential implications for cell biology and viral pathogenesis.

PMID- 12495846
TI  - PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to
      disease.
AB  - The phosphatase and tensin homolog deleted on chromosome ten (PTEN) and
      myotubularin (MTM1) represent subfamilies of protein tyrosine phosphatases whose
      principal physiological substrates are D3-phosphorylated inositol phospholipids.
      As lipid phosphatases, PTEN- and MTM1-related (MTMR) proteins dephosphorylate the
      products of phosphoinositide 3-kinases and antagonize downstream effectors that
      utilize 3-phosphoinositides as ligands for protein targeting domains or
      allosteric activation. Here, we describe the cellular mechanisms of PTEN and MTMR
      function and their role in the etiology of cancer and other human diseases.

PMID- 12495847
TI  - Kinesin motors and disease.
AB  - Kinesins are motor proteins that move cargoes such as vesicles, organelles and
      chromosomes along microtubules. They are best known for their role in axonal
      transport and in mitosis. There is a diverse family of kinesins, members of which
      differ in composition and functions. Roles of kinesins in diseases typically
      involve defective transport of cell components, transport of pathogens, or cell
      division.

PMID- 12495848
TI  - The nuclear lamina and inherited disease.
AB  - Inherited disorders of the nuclear lamina present some of the most intriguing
      puzzles in cell biology. Mutations in lamin A and lamin C - nuclear intermediate
      filament proteins that are expressed in nearly all somatic cells - cause tissue
      specific diseases that affect striated muscle, adipose tissue and peripheral
      nerve or skeletal development. Recent studies provide clues about how different
      mutations in these proteins cause either muscle disease or partial lipodystrophy.
      Although the precise pathogenic mechanisms are currently unknown, the involvement
      of lamins in several different disorders shows that research on the nuclear
      lamina will shed light on common human pathologies.

PMID- 12495849
TI  - ADF/cofilin and actin dynamics in disease.
AB  - ADF/cofilins are key regulators of actin dynamics in normal cells. Recent
      findings suggest that, under cellular stress, the wild-type proteins might form
      complexes with actin that can alter cell function. Owing to their rapid
      formation, these complexes might initiate or aid in the progression of diseases
      as diverse as Alzheimer's disease and ischemic kidney disease. Although evidence
      for their involvement in diseases other than Alzheimer's and ischemic kidney
      disease is tenuous, recent studies suggest that altered production, regulation or
      localization of these proteins might lead to cognitive impairment, inflammation,
      infertility, immune deficiencies and other pathophysiological defects.

PMID- 12495850
TI  - Endocytosis and sorting of glycosphingolipids in sphingolipid storage disease.
AB  - Recent studies on the endocytic itinerary of glycosphingolipids (GSLs) in
      sphingolipid storage disease (SLSD) fibroblasts have yielded new insights into
      the mechanisms underlying the endocytosis and intracellular sorting of lipids in
      normal and disease cells. Here we highlight new data on clathrin-independent
      endocytosis of GSLs, the involvement of sphingolipid-cholesterol interactions in
      perturbation of endocytic trafficking, and potential roles for rab proteins in
      regulation of GSL transport in SLSDs.

PMID- 12495852
TI  - A tale of two C2 domains.

PMID- 12495854
TI  - Drooling and stuttering, or do synapses whisper?

PMID- 12495853
TI  - Ubiquitin and synaptic dysfunction: ataxic mice highlight new common themes in
      neurological disease.

PMID- 12495855
TI  - An activity-dependent spermine-mediated mechanism that modulates glutamate
      transmission.

PMID- 12495856
TI  - Linking reward expectation to behavior in the basal ganglia.

PMID- 12495857
TI  - A prominent role for intrinsic neuronal properties in temporal coding.

PMID- 12495858
TI  - Acupuncture: neuropeptide release produced by electrical stimulation of different
      frequencies.

PMID- 12495859
TI  - Improbable areas in the visual brain.

PMID- 12495860
TI  - A common architecture for K+ channels and ionotropic glutamate receptors?

PMID- 12495861
TI  - Dissecting the circuitry of the auditory system.

PMID- 12495862
TI  - Wnt-frizzled signaling in neural crest formation.

PMID- 12495863
TI  - Eph signaling: a structural view.
AB  - Eph receptors, the largest subfamily of receptor tyrosine kinases, and their
      ephrin ligands are important mediators of cell-cell communication regulating cell
      attachment, shape and mobility. Both Ephs and ephrins are membrane-bound and
      their interactions at sites of cell-cell contact initiate unique bidirectional
      signaling cascades, with information transduced in both the receptor-expressing
      and the ligand-expressing cells. Recent structural and biophysical studies
      summarized in this review reveal unique molecular features not previously
      observed in any other receptor-ligand families and explain many of the
      biochemical and signaling properties of Ephs and ephrins. Of particular
      importance is the insight into how approximation of ligand-expressing and
      receptor-expressing cells could lead to the formation and activation of highly
      ordered signaling centers at cell-cell interfaces.

PMID- 12495870
TI  - The basal ganglia and the epilepsies: translating experimental concepts to new
      therapies.

PMID- 12495871
TI  - Functional organization of the circuits connecting the cerebral cortex and the
      basal ganglia: implications for the role of the basal ganglia in epilepsy.
AB  - The basal ganglia are composed of a set of forebrain structures implicated in the
      adaptive control of behaviour. These structures process information originating
      from the entire cerebral cortex, as well as from nonspecific thalamic nuclei and
      the amygdala. In turn, they redistribute the integrated signals toward thalamic
      and brainstem nuclei related to motor, premotor, prefrontal and limbic cortical
      areas. During the two last decades, there has been increasing experimental
      evidence that the basal ganglia circuitry may be part of a remote control system
      influencing the spread of epileptic seizures. In the present article, we review
      the basic principles of the functional organization of the basal ganglia and
      provide experimental data on the activity that is transmitted by the cerebral
      cortex to the input stage of the basal ganglia during absence seizures. The
      functional organization of the basal ganglia supports the current hypothesis that
      these structures can dynamically control generalized seizures through their input
      output relationships.

PMID- 12495872
TI  - Normal functional imaging of the basal ganglia.
AB  - In non-human primates, all cortical projections into the striatum are
      topographically organized in discrete parallel circuits. These circuits are
      involved in distinct behavioral functions. In humans, functional imaging data
      support a similar organization of the striatum. The representation of the
      different elements of a motor act (such as movement learning, selection, mental
      representation, preparation and execution) are represented differentially along
      distinct cortico-basal ganglia circuits. Saccadic eye movements are predominantly
      represented in the caudate nucleus. Motivational processes are represented in the
      ventral part of the striatum. Thus, functional imaging data suggest that the
      human striatum is organized in parallel motor circuits similar to those found in
      animal studies.

PMID- 12495873
TI  - Relationship between oscillations in the basal ganglia and synchronization of
      cortical activity.
AB  - The functions of oscillations within the basal ganglia are poorly understood. We
      discuss in the present paper, the possible physiological or pathological roles of
      oscillatory activities within the basal ganglia, and their relationship to
      cortical oscillations. Three aspects are presented: 1. What do we know from
      animal studies? 2. What do we know from neurophysiological studies in
      parkinsonian patients? 3. What is the effect of L-dopa treatment and electrical
      stimulation within basal ganglia circuits on cortical oscillations? Animal
      studies suggest that neuronal oscillations are spontaneously generated within the
      basal ganglia system, especially from the GPE and the subthalamic nucleus (STN),
      but are mainly synchronized by cortical activity via the striatal inputs.
      Dopamine depletion results in a global increase of oscillations within the whole
      basal ganglia system, particularly in the GP-NST network. Oscillations within the
      basal ganglia may, in part, be related to tremor since they are enhanced,
      especially in the globus pallidus internus (GPI) and the STN, in human and animal
      dopaminergic depletion. However, they also play a role in the physiology of
      movement as revealed by coherence analysis between cortex, muscles and GPI/STN in
      parkinsonian patients undergoing deep brain stimulation. It is known that the
      basal ganglia may influence cortico-muscular oscillations such as the Piper
      rhythm and other rhythms in the beta band. In off-drug parkinsonian patients, low
      frequency oscillations (4-10 Hz) are favoured, presumably resulting in
      bradykinesia and low force. When medically (Ldopa) or surgically (deep brain
      stimulation) treated, these low frequency oscillations are replaced by high
      frequency (70 Hz) oscillations that are important for motor programs to be
      correctly executed. Studies of cortical reactivity related to planning of
      voluntary movement in parkinsonian patients provide evidence that it is possible
      to influence cortical reactivity through the basal ganglia system.

PMID- 12495874
TI  - Seizures and the basal ganglia: a review of the clinical data.
AB  - This article attempts an overview of the clinical and electrophysiological
      evidence supporting the involvement of the basal ganglia in epileptic seizures.
      In contrast to animal data, evidence for a role of these structures in human
      epilepsies is lacking. However, from the theoretical point of view, it remains
      conceivable that, given their strong interconnectivity, basal ganglia could be
      functionally linked to the cerebral cortex during an epileptic seizure. Several
      clinical ictal aspects have been suggested to be compatible with the involvement
      of basal ganglia, namely, ictal dystonic posturing during temporal lobe seizures,
      rotatory seizures and paroxysmal dyskinesia-like seizures. On the other hand,
      basal ganglia dysfunction may also influence some aspects of epilepsy, as
      suggested by pure basal ganglia pathology such as Parkinson's disease, or the
      described effect of an acute basal ganglia lesion in epileptic patients. The data
      discussed in this review may stimulate further research to link basic scientific
      data to human epilepsies, and lead to the development of novel therapeutical
      solutions.

PMID- 12495875
TI  - PET imaging in epilepsy: basal ganglia and thalamic involvement.
AB  - Positron emission tomography imaging has revealed basal ganglia and thalamic
      abnormalities in cerebral blood flow, metabolism and neurotransmission in
      patients with partial epilepsy. Although these changes remain of uncertain
      significance, this involvement could be associated with the initiation,
      propagation or control of seizures. This paper will review the imaging data
      obtained using positron emission tomography in patients with partial and
      generalized epilepsy.

PMID- 12495876
TI  - The control of seizures by the basal ganglia? A review of experimental data.
AB  - Over the past few years, the role of the basal ganglia in epilepsy has been
      widely debated, the debate being mainly based on experimental data obtained from
      several animal models. In the present review, the possibility that basal ganglia
      circuits can generate some forms of seizure or participate to their initiation
      will first be addressed. In the second part of this chapter, recent data
      suggesting the involvement of the basal ganglia in the control of seizures will
      be discussed. Although it is clear that basal ganglia circuits cannot generate
      seizures and are unlikely to be involved in their initiation, numerous
      experimental data have revealed that seizures modify the activity of this system.
      More recently, the collection of pharmacological and electrophysiological data in
      animal models of epilepsy has led to the emergence of the basal ganglia as a
      possible control circuit for the seizures. These experimental data have already
      led to initial clinical trials in epileptic patients. The preliminary clinical
      data encourage the further development of experimental research in chronic models
      of epilepsy to better determine the exact output circuits involved in seizure
      interruption, the mechanisms participating in seizure control and whether the
      same circuits are involved in the control of different types of seizures. These
      studies may allow the identification of crucial structures and the types of
      epilepsy likely to benefit from this new therapeutic approach.

PMID- 12495877
TI  - Developmental aspects of the basal ganglia and therapeutic perspectives.
AB  - Development and sex hormones play an important role in the expression of
      seizures. Sex-specific differences in the development of seizure suppressing
      neuronal networks may account, at least in part, for age- and sex related
      susceptibility to seizures. The substantia nigra pars reticulata is a site
      involved in the control of seizures. In adult male rats, there are two distinct
      GABAA sensitive regions within the substantia nigra pars reticulata, which
      mediate opposite effects in flurothyl seizures. Muscimol infused into the
      anterior region is anticonvulsant while similar infusions into the posterior
      region are proconvulsant. These two regions differ morphologically, and utilize
      different efferent networks. In contrast, in postnatal day 15 male rats, there is
      no such differentiation and muscimol infusions have only proconvulsant effects.
      The hallmark of the female substantia nigra pars reticulata is the fact that
      muscimol- mediated proconvulsant effects cannot be demonstrated in any region at
      any age. The sex-related difference in nigral seizure control may be related to
      the lack of testosterone in females. Accordingly, neonatal castration of males
      results in the loss of the proconvulsant region. The male type of the substantia
      nigra pars reticulata effects can be induced by exogenous testosterone
      administration in neonatally castrated male or in female rats. The phenotype of
      nigral GABAergic neurons, as characterized by GABAA receptor subunit composition,
      muscimol-induced electrophysiological responses, and connectivity of output
      networks may each be altered by the presence of testosterone. Better
      understanding of the influence of the endocrine system on brain development and
      neuronal activity may provide new insight into the treatment of age- and sex
      dependent seizure disorders.

PMID- 12495878
TI  - Deep brain stimulation in epilepsy with particular reference to the subthalamic
      nucleus.
AB  - Alternative methods, for the treatment of medically refractory epileptic
      patients, who cannot be treated by resective surgery, such as chronic deep brain
      neurostimulation, are under development. Such methods have been used in the
      cerebellum, various thalamic nuclei, and in the caudate nucleus. In Grenoble,
      encouraged by the suppressive effects of pharmacological or electrical inhibition
      of the STN on different types of seizure in animal models of epilepsy, and by our
      experience with STN high frequency stimulation (HFS) in patients with movement
      disorders, we have evaluated the high frequency stimulation of the subthalamic
      nucleus (STN HFS). STN HFS was performed in five patients suffering from
      medically intractable seizures and considered unsuitable for resective surgery. A
      67% to 80% reduction in seizure frequency was observed in three patients, with a
      partial symptomatic epilepsy of the central region. An additional patient
      suffering from severe myoclonic epilepsy (Dravet syndrome) also responded to STN
      HFS, with a weaker reduction of seizure frequency. The fifth patient who suffered
      from an autosomal dominant frontal lobe epilepsy with insulo-frontal seizures did
      not show any improvement. These results suggest that stimulation of STN could be
      a promising treatment for patients with drug-resistant epilepsy who would not
      benefit from conventional surgery.

PMID- 12495879
TI  - [CHEK2 and breast cancer risk].
AB  - The BRCA1 et BRCA2 genes are involved in 2/3 of genetic predisposition with major
      risk of breast cancer. One or more genes remain to be identified. The CHEK2 gene
      is a good candidate. The CHEK2 gene mutation 1100delC is associated with a
      moderate increase of breast cancer risk (RR = 2). CHEK2 is probably one of the
      genetic factors associated with moderate risk, but however when associated with
      other variants, it could explain some familial breast cancer and sporadic cancer
      cases. It seems to be too early to include CHEK2 in genetic counselling at the
      present time.

PMID- 12495880
TI  - [Integrins, cell response to anti-tumor agents and chemoresistance].
AB  - Integrins are a family of heterodimeric transmembrane receptors that mediate cell
      cell and cell-extracellular matrix adhesion. Integrin-mediated signaling is
      essential for the regulation of fundamental cellular functions, including
      proliferation and survival, and for tumor development. According to in vitro
      studies, integrin ligation by extracellular matrix proteins can modulate the
      cytotoxicity of anti-tumor agents, in a cell-type sensitive manner. Underlying
      molecular mechanisms are not well understood, but may be based on the
      interrelations between integrin signaling pathways and pathways that control cell
      cycle and apoptosis. On the other hand, alterations of integrin expression and/or
      function have been observed during the acquisition of chemoresistance in cells
      chronically exposed to cytotoxic agents. These data are in favor of a role of
      integrins in chemoresistance processes, and open new perspectives in the field of
      cancer therapy and prognosis.

PMID- 12495881
TI  - [General principles of treatment of anemia in cancer patients].
AB  - Most of cancer patients experience anemia. It's a main cause of fatigue and it
      leads to a decrease of the quality of life. It may have an impact on prognostic
      too, mainly when radiotherapy is concerned. Apart from etiologic treatments,
      anemia can be treated with transfusion and/or erythropoietin. Their respective
      pros and cons are discussed. There are few guidelines available on this topic and
      an algorithm of decision is proposed.

PMID- 12495882
TI  - [Evaluation of platinum contamination of a hazardous drug preparation area in a
      hospital pharmacy].
AB  - In our hospital, in accordance with recommendations for personnel protection,
      hazardous drugs are prepared in a class II biological safety cabinet (BSC)
      located in a specific area of the pharmacy. The aim of this study was to validate
      the efficiency of this unit in personnel protection by measuring levels of
      platinum in the working environment (platinum being the most common
      antineoplastic agent used in this hospital). Two series of surface sampling were
      conducted, preparation guidelines were changed for parts after first results have
      been completed. Performance of the sampling method is about 35%. Platinum was
      measured by atomic absorption spectrophotometry technique. The analytical
      detection limit was 10 mug/L of platinum and was sufficient to detect less than
      one micro-drop of cisplatinum solution (1 mg/mL). Platinum was found inside the
      BSC at the end of the working day: 2 to 998 pg/cm2 or 2 to 20 ppm of the total
      cisplatinum handled. All samples outside the BSC showed little (less than the
      detection limit) or no contamination. Gloves were often contaminated, either by
      contaminated commercial drug vials or through handling errors. Working guidelines
      changes did not lead to the absence contamination on surfaces. Gloves should
      therefore be changed frequently (every 15 min), personnel training should be
      regularly re-evaluated, BSC and rooms should be thoroughly cleaned every day. In
      this way, a centralized unit provides total protection from exposure to hazardous
      drugs.

PMID- 12495883
TI  - [Mammography use among women aged 35 to 75 years].
AB  - The aim of the study was to evaluate mammography use and indications (diagnosis
      or screening) among 19,253 women aged 35 to 75 attending a health screening
      centre. The data were collected by a self-administered questionnaire completed
      after by an interview with a nurse. Mammography use is frequent in women
      attending a health screening centre, even before the age of 50: 79.1% had
      undergone at least one mammography during their life and for 47.3% a screen had
      been performed within the last three years. Nevertheless mammography was only
      used by 65.2% of the women aged 50-69 years, target age group of the screening
      programme. A logistic regression model adjusting for multiple variables was used
      to examine factors associated with women who underwent a screen within the last
      three years. Women more likely to be screened were aged 50-69 (vs age 35-49:
      OR=3.1), used regular gynaecological care (OR=4.5), had a family history of
      breast cancer (OR=1.45), had in their district a breast cancer screening campaign
      (OR=1.93). The study indicated that women under 50 years of age with a family
      history of breast cancer and women aged 70 and over were under-screened. When a
      campaign for breast cancer screening was organised in the district the screening
      rates were higher in the target population (71,4% vs 60,1%) although only 64% of
      the women reported having attended. Current recommendations for breast cancer
      screening should be reviewed in the light of these results.

PMID- 12495884
TI  - [MR imaging of endometrial carcinoma: role and limits].
AB  - PURPOSE: To assess the MR imaging (MRI) in initial decision making of endometrial
      carcinoma. PATIENTS AND METHODS: From january 1997 to march 2002, 86 patients
      with clinical stage I endometrial carcinoma were studied by pelvic (22) or
      abdomino-pelvic (64) MRI. The size and signal of lesions and junctional zone, the
      enhancement after contrast administration, the associated benign lesions and the
      pelvic and lumbo-aortic lymph nodes were assessed without knowledge of surgical
      results in viewing to identify pitfalls in MRI staging. RESULTS: MRI allows
      correct staging in 81.4% (70/86) of cases. Nine cases of false negative on T2
      weighted images were correctly staged after contrast administration and dynamic
      study. Limits of MRI are due to presence of thin or lack of junctional zone,
      polyps, myomas, adenomyosis, intra cavitary bleeding, and myometrium thinning by
      large tumors. Eighteen patients were N+, with MRI sensitivity of 82% and
      specificity of 94%. CONCLUSION: MRI is the best modality for pretherapeutic
      assessment of endometrial carcinoma. MRI allows to choose type of surgery:
      laparoscopy or laparotomy and define volume of radiotherapy.

PMID- 12495885
TI  - [Usefulness of the French DRG based information system (PMSI) in the measurement
      of cancer activity in a multidisciplinary hospital: the Hospices Civils de Lyon].
AB  - Measuring the burden of cancer activity in big teaching multidisciplinary
      hospitals becomes a real challenge in France for organizational, quality of care
      and economic reasons. At the "Hospices Civils de Lyon" University Hospital in
      France, we have chosen to face this question by using the french DRG based
      information system called PMSI. It allows to identify hospital stays related to
      cancer care through the use of an algorithm based on selected ICD 10 codes for
      hospital stay. We then estimate the proportion of patients concerned by cancer
      and classify hospital stays and patients according to various epidemiological and
      clinical parameters. The results for the year 1999 taken as an example showed
      that 43,883 out of 293,827 (15%) of hospital stays were related with a diagnostic
      of cancer, corresponding to 12,777 different patients. The concordance study on
      154 patients between the data from the electronic PMSI files and medical paper
      records showed a 97% concordance for cancer diagnosis and 93% for the precise
      type of tumor. In absence of hospital based cancer registries, the PMSI data base
      gives an accurate source of information for cancer burden and provides many
      potential applications in defining hospital policies for cancer management and
      resource allocations.

PMID- 12495886
TI  - [A study based on national DRG data to evaluate work load, practice and cost
      relating to paediatric oncology in French hospitals].
AB  - OBJECTIVES: To assess if our methodology previously used for all cancers remains
      valid when only 1% of cancers are analysed, we used childhood cancer in French
      hospitals based on national DRG data. MATERIALS AND METHODS: With a specific
      algorithm we extracted from the 1999 national DRG data (16,539,352
      hospitalisations) the cancer data (2,947,471 hospitalisations) and the reduced
      cancer data (2,711,025 hospitalisations). We used this reduced cancer data to
      identify the 77 350 hospitalisations for childhood cancers. RESULTS: The majority
      of hospitalisations (83%) and the Activity Synthetic Index (ISA) for childhood
      cancers are concentrated on University hospitals and regional cancer centres. The
      cost of childhood cancers was estimated to be 136 million euros, with haematology
      costing 60 million euros. Chemotherapy, which accounted for almost 50% of the ISA
      is the predominant therapy. DISCUSSION AND CONCLUSION: Our results appear to be
      consistent with the incidence and the clinical practices described by the
      population registries and the registry of the French Society for Paediatric
      Oncology. They correspond also with the organisation of the care of those
      patients which converges towards the global care of the patient in which the
      concept of health networks and patient's trajectories are pivotal. However, an
      investigation inside the hospitals is required to see if our results correspond
      with the reality. This is the objective of our next study.

PMID- 12495887
TI  - [44th meeting of the American Society of Therapeutic Radiology and Oncology
      (Astro): New Orleans, 6-10 October 2002].

PMID- 12495888
TI  - [A good RUM (resumes d'unite medicale) is better than two "you will have"!].

PMID- 12495889
TI  - [Surgery or surveillance for limited prostate cancer?].

PMID- 12495892
TI  - Is chronic lymphocytic leukemia one disease?

PMID- 12495893
TI  - Is chronic lymphocytic leukemia one disease?

PMID- 12495894
TI  - Management of primary mediastinal B-cell lymphoma with sclerosis: advances and
      caveats.

PMID- 12495895
TI  - Guidelines in hematology.

PMID- 12495896
TI  - Practice guidelines for the therapy of primary myelodysplastic syndromes: a word
      of caution about their translation into clinical practice.

PMID- 12495897
TI  - Lyn kinase is activated following thrombopoietin stimulation of the
      megakaryocytic cell line B1647.
AB  - BACKGROUND AND OBJECTIVES: B1647 is a cell line derived from bone marrow cells of
      a patient with acute myeloid leukemia (M2) with a complete erythro-megakaryocytic
      phenotype and bears both k and p isoforms of c-mpl. Interestingly, spontaneous
      B1647 cell proliferation is significantly potentiated by thrombopoietin (TPO).
      DESIGN AND METHODS: We aimed to evaluate the proliferative signal transduction
      events following the activation of c-mpl and we stimulated B1647 cells with TPO
      40 ng/mL for 3, 7, 15 and 30 minutes; cells were then lysed and whole lysates
      were immunoprecipitated with anti-phosphotyrosine antibodies. RESULTS: In our
      hands, TPO stimulation induced phosphorylation of several substrate proteins in
      B1647 cells. The increase in tyrosine phosphorylation from background spontaneous
      activation was transient, maximal after 10 minutes and declined to reach
      constitutive levels after 30 minutes. In particular, protein substrates between
      50 and 140 kDa appeared to be selectively phosphorylated by TPO. We demonstrated
      that Jak2, Stat3 and Shc were activated in B1647 cells after TPO, as already
      shown for different cell lines by other authors. Moreover, Lyn kinase activation
      was detected. Grb2 co-immunoprecipitated with phosphorylated proteins. The
      phosphorylation of Syk kinase was not demonstrated, whereas Vav was activated by
      TPO. INTERPRETATION AND CONCLUSIONS: The pattern of protein phosphorylation
      determined in B1647 cells by TPO testifies the role of this cytokine in
      sustaining cell growth and indicates Lyn tyrosine kinase as a possible target
      protein in transduction of the TPO proliferative signal.

PMID- 12495898
TI  - Development of reference ranges in elite athletes for markers of altered
      erythropoiesis.
AB  - BACKGROUND AND OBJECTIVES: Our previous research developed two statistical models
      that are useful indicators of current (ON-model) or recently discontinued (OFF
      model) recombinant human erythropoietin (rHuEPO) use by athletes. The component
      variables of the ON-model are hematocrit (Hct), reticulocyte hematocrit (RetHct),
      serum erythropoietin (EPO), percent macrocytes (%Macro), and soluble transferrin
      receptor (sTfr), whilst the OFF-model uses only the first three variables.
      Genetics and training modalities of elite athletes may conceivably produce
      unusual values for blood parameters related to erythropoiesis. The aims of this
      study were to develop reference ranges in elite athletes for key hematologic
      parameters as well as ON- and OFF-models scores, and to evaluate the effect of
      ethnicity, gender, residence at moderate altitude (approximately 2000 m) and
      within-individual variation on the variables and model scores. DESIGN AND
      METHODS: Over a period of three weeks, 413 female and 739 male elite athletes
      from 12 countries visited laboratories to provide three blood samples for
      analysis of blood parameters sensitive to erythropoiesis. For each parameter and
      for the ON- and OFF-model scores, we used mixed modeling to establish the range
      within which we could be 95% certain that the value for a randomly chosen athlete
      would fall, taking into account various random effects (variation within and
      between subjects and laboratories) and fixed effects (means for different levels
      of ethnicity, age, sport, altitude of residency). We performed similar analyses
      for changes in the ON- and OFF-model scores between the three visits. RESULTS:
      Most fixed effects were accompanied by clear-cut, small to moderate differences
      in several parameters. However, residency at moderate altitude was accompanied by
      a much higher hematocrit than residency nearer sea level, with the mean (and 95%
      confidence limits) for the difference being 2.3 (0.9 to 3.7) and 1.8 (0.1 to 3.5)
      units for males and females, respectively. Males at altitude also demonstrated a
      moderately higher ON-model score. Otherwise the influence of these effects was
      small for ON-, OFF- and changes in model scores. INTERPRETATION AND CONCLUSIONS:
      Assessment of an athlete's blood parameters and ON- and OFF-model scores may need
      adjustment for training modalities and other characteristics of the subject.
      Changes in model scores (together with monitoring of urine samples for the
      presence of rHuEPO) provide a promising approach to detection of rHuEPO abuse,
      because they are less sensitive to subject characteristics and less variable than
      raw model scores.

PMID- 12495899
TI  - Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma
      with sclerosis: a retrospective multinational study on 426 previously untreated
      patients.
AB  - BACKGROUND AND OBJECTIVES: This multinational retrospective study compares the
      outcomes of patients with primary mediastinal large B-cell lymphoma (PMLBCL) with
      sclerosis after first-generation (dose-intensive regimens), third-generation
      (alternating regimens) and high-dose chemotherapy strategies, frequently with
      adjuvant radiation therapy. DESIGN AND METHODS: Between August 1981 and December
      1999, a total of 426 previously untreated patients with confirmed diagnosis were
      enrolled in 20 institutions to receive combination chemotherapy with either first
      generation (CHOP or CHOP-like) regimens, third generation (MACOP-B, VACOP-B,
      ProMACE CytaBOM) regimens or high-dose chemotherapy (HDS/ABMT). RESULTS: With
      chemotherapy, complete response (CR) rates were 49% (50/105), 51% (142/277) and
      53% (23/44) with first generation, third generation and high-dose chemotherapy
      strategies, respectively; partial response (PR) rates were 32%, 36% and 35%,
      respectively. All patients who achieved CR and 124/142 (84%) with PR had
      radiation therapy on the mediastinum. The final CR rates became 61% for CHOP/CHOP
      like regimens, 79% for MACOP-B and other regimens, and 75% for HDS/ABMT. After
      median follow-ups from attaining CR of 48.5 months for CHOP/CHOP-like regimens,
      51.7 months for MACOP-B type regimens and 32.4 months for HDS/ABMT, relapses
      occurred in 15/64 (23%), 27/218 (12%) and 0/33 (0%) patients, respectively.
      Projected 10-year progression-free survival rates were 35%, 67% and 78%,
      respectively (p=0.0000). Projected 10-year overall survival rates were 44%, 71%
      and 77%, respectively (p=0.0000), after median follow-ups from diagnosis of 52.3
      months, 54.9 months and 35.8 months, respectively. INTERPRETATION AND
      CONCLUSIONS: In patients with PMLBCL with sclerosis, MACOP-B plus radiation
      therapy may be a better strategy than other treatments; these retrospective data
      need to be confirmed by prospective studies. The encouraging survival results
      after high dose chemotherapy require confirmation in selected high-risk patients.

PMID- 12495900
TI  - Discrepant sensitivity of thromboplastin reagents to clotting factor levels
      explored by the prothrombin time in patients on stable oral anticoagulant
      treatment: impact on the international normalized ratio system.
AB  - BACKGROUND AND OBJECTIVES: We tested the principle of local International
      Normalized Ratio (INR) calibration using INR calibrator plasmas (PT Calibration
      Plasma Kit, Behring), two thomboplastin reagents (Neoplastin plus, rabbit brain,
      Stago, and Recombiplastin, recombinant human tissue factor, Ortho Diagnostics)
      and the same coagulometer (STA, Stago) on 92 patients on stable oral
      anticoagulant treatment. DESIGN AND METHODS: A four-point calibration was
      obtained with each reagent by linear regression (sec/INR) on a log-log scale (r >
      or = 0.999). The bias between the two reagents (Recombiplastin - Neoplastin Plus)
      was reduced from 31.7% to 17.5% and 7.5% (p=0.001) when results were expressed,
      respectively, as PT ratio (using the mean normal prothrombin time as denominator
      term), INR (using instrument-specific ISI supplied by the manufacturers) and
      calibrated INR, but there was a consistently significant regression of the
      differences over the average values even after log transformation (r > or =
      0.586). The bias between the reagents was reduced to 1% (p=ns) when assuming
      Recombiplastin as the reference thromboplastin and applying Tomenson's
      correction, but limits of agreements were as large as 20%. Factor VII, X, V and
      II activity was measured with the two thromboplastin reagents in all plasma
      samples using immunodepleted plasmas (Stago). RESULTS: Statistically significant
      biases were observed for all clotting factors with the two reagents
      (Recombiplastin Neoplastin Plus) and ranged from 3.5 % (FII) to 37.2% (FVII). In
      addition, for FVII and FV there was a significant regression of the difference
      over the average value (after log-transformation, r > or = 0.282). The patients
      were divided into 3 groups according to their degree of anticoagulation (INR
      <2.0; INR between 2.0 and 3.5; INR >3.5). Factor levels differed significantly
      with the two reagents throughout the 3 groups of patients. In addition, the
      relative distributions of the 3 vitamin K-dependent factors also differed in the
      3 groups with the two thromboplastin reagents. INTERPRETATION AND CONCLUSIONS:
      The discrepant sensitivity to factor VII, X and V levels of the two
      thromboplastin reagents explored in this study prevents INR calibration with
      commercially available calibrator plasmas and is responsible for a significant
      variability in INR values even under optimal conditions of INR calibration.

PMID- 12495901
TI  - Clinical benefits of granulocyte colony-stimulating factor therapy after
      hematopoietic stem cell transplant in children: results of a prospective
      randomized trial.
AB  - BACKGROUND AND OBJECTIVES: Hematopoietic stem cell transplantation (HSCT) is
      associated with profound neutropenia and significant morbidity and mortality. To
      evaluate the safety and efficacy of non-glycosylated recombinant human
      granulocyte colony-stimulating factor (rHuG-CSF) in accelerating myeloid recovery
      and its influence on infections, supportive therapy, and transplant-related
      mortality we carried out a randomized study in pediatric patients receiving HSCT.
      DESIGN AND METHODS: Two hundred and twenty-one consecutive children, recipients
      of an allogeneic or autologous bone marrow (BM) or peripheral blood progenitor
      cell (PBPC) transplant, were randomized to either receive rHuG-CSF 10 mg/kg
      (n=110) or not (n=111). RESULTS: Myeloid engraftment was faster in the treated
      arm (14 vs 20 days, p=0.0001). Neutrophil recovery was accelerated both in the BM
      subgroups (allogeneic and autologous, p=0.002) and in the PBPC group (p=0.0005).
      All the other evaluated variables showed an advantage in favor of rHuG-CSF
      treated patients that was significant for platelet transfusion independence and
      time to discharge (p=0.02 and p=0.04, respectively) only in the BM subgroup.
      INTERPRETATION AND CONCLUSIONS: We conclude that faster neutrophil recovery in BM
      recipients receiving rHuG-CSF led to clinical benefits, while, in the PBPC
      subgroup, it did not translate into clinical advantages.

PMID- 12495902
TI  - Quality of life in patients randomized to receive a bone marrow or a peripheral
      blood allograft.
AB  - BACKGROUND AND OBJECTIVES: Quality of life (QOL) is an important clinical end
      point to be considered in the late follow-up of patients treated with allogeneic
      bone marrow (BM) or peripheral blood progenitor cell (PBPC) transplantation.
      DESIGN AND METHODS: To assess the QOL in a group of survivors of hematologic
      malignancies who had been enrolled in a prospective randomized trial comparing
      allogeneic BM with PBPC. Sixty randomized patients had been enrolled in a study
      comparing BM with PBPC graft during 1995-99. At the time of this QOL study, 30
      were alive and 26 (13 BM and 13 PBPC) were eligible. Clinical and demographic
      data were collected and psychometric instruments (WHOQOL-100 and the Hospital
      Anxiety and Depression Scale HAD) were used. Non-parametric and univariate
      analyses were performed. RESULTS: The PBPC recipients had more chronic graft
      versus-host disease (p=0.03) and were on immunosuppressive treatment for a longer
      period (p=0.02). The WHOQOL-100 analysis demonstrated significant differences
      between groups with more favorable results in the BM group in the facets of Pain
      and Discomfort (p=0.03), Mobility (p=0.02) and Daily Living Activities (p=0.03).
      According to the patients' spontaneous responses, 8 individuals (6 in the PBPC
      group) believed that their QOL had worsened. INTERPRETATION AND CONCLUSIONS: With
      the limitations of a small randomized study, these findings suggest a lower QOL
      in recipients of allogeneic PBPC than in recipients of BM grafts, probably due to
      the frequency and severity of chronic graft-versus-host disease. This need to be
      confirmed in a large international trial.

PMID- 12495903
TI  - Evidence- and consensus-based practice guidelines for the therapy of primary
      myelodysplastic syndromes. A statement from the Italian Society of Hematology.
AB  - BACKGROUND AND OBJECTIVES: Novel therapeutic agents and strategies have been
      introduced into the management of myelodysplastic syndromes (MDS) in the last
      years. This has led to more treatment options and a better chance of long-term
      survival for MDS patients, but also to uncertainty regarding the optimal use and
      possible side effects of these treatments. The Italian Society of Hematology
      commissioned a project to develop guidelines for the therapy of MDS using
      evidence-based knowledge and consensus-formation techniques. DESIGN AND METHODS:
      An Advisory Council (AC) shaped the project around a series of key clinical
      questions, performed a systematic search for evidence and graded the available
      evidence according to the Scottish Intercollegiate Guidelines Network (SIGN). A
      list of clinical questions was mailed to each of 10 senior hematologists
      composing the Expert Panel (EP): the panelists were asked to rank the most
      relevant questions, and to formulate answers to the questions according to the
      tables of evidence. A scenario phase followed, so as to reach a consensus on the
      three top ranked questions. The EP was asked to score patient profiles as
      appropriate or not appropriate for the therapeutic strategy under scrutiny,
      according to the RAND technique. Finally, from September 2001 to January 2002,
      four Consensus Conferences conducted according to the Nominal Group Technique
      were held in Milan, Italy. The overall goal of the conferences was to take a
      final decision upon the appropriateness of the uncertain scenarios and of the
      uncertain responses to the clinical questions. RESULTS: Evidence was judged
      sufficient for providing recommendations on the use of allogeneic stem cell
      transplantation, leukemia-like chemotherapy, autologous stem cell
      transplantation, low-dose chemotherapy, danazol, immunosuppressive therapy,
      hypomethylating agents and hematopoietic growth factors. Specific recommendations
      for supportive therapy, including iron chelation, were issued. Allogeneic stem
      cell transplantation was unanimously considered as the only curative treatment
      for MDS patients, and recommendations on its use were agreed based on patient's
      age, risk, clinical features and donor availability. AML-like chemotherapy was
      also considered a valuable therapeutic option for subsets of MDS patients.
      Autologous stem cell transplantation was recommended for patients who lack an HLA
      identical donor and have achieved complete remission with AML-like chemotherapy.
      Decitabine, recombinant human erythropoietin and immunosuppressive therapy were
      judged valuable therapeutic options for subsets of MDS patients whereas low-dose
      cytarabine was not. Specific therapeutic strategies for those subjects younger
      than 18 years or older than 75 years and the strategy of watchful waiting were
      decided by patient-oriented questions. INTERPRETATION AND CONCLUSIONS: Using
      evidence and consensus, recommendations for the treatment of MDS were issued.
      Statements were graded according to the strength of the supporting evidence and
      uncertainty was explicitly declared.

PMID- 12495904
TI  - Core binding factor genes and human leukemia.
AB  - BACKGROUND: The core binding factor (CBF) transcription complex, consisting of
      the interacting proteins RUNX1 and CBFb, is essential for normal hematopoiesis.
      Recent studies have shown that mutations and gene rearrangements involving this
      complex are frequently implicated in leukemogenesis. Understanding the molecular
      events leading to the disruption of CBF has provided important insights into our
      understanding of the normal regulatory pathways that control hematopoiesis and
      has begun to reveal how alterations in these pathways induce leukemia.
      INFORMATION SOURCES: Both authors are involved in the identification and
      characterization of chromosomal abnormalities associated with hematologic
      malignancy. This has led to contributions to multicenter clinical and laboratory
      investigations as well as publications in peer-reviewed journals. All of the
      references cited in this review are published in journals covered by Medline.
      State of the Art. The core binding factor (CBF) is a heterodimeric transcription
      factor composed of the RUNX1 and CBFb subunits. RUNX1 is the DNA binding element
      of the complex and its affinity is greatly increased in the presence of CBFb.
      Knock-out studies in mice have demonstrated that both RUNX1 and CBFb are
      necessary for definitive hematopoiesis. Furthermore, reciprocal chromosomal
      translocations involving both partners have been directly implicated in
      leukemogenesis. Evidence is now emerging that at least some of the resulting
      fusion proteins, namely ETV6-RUNX1, RUNX1-MTG8 and CBFb-MYH11 dominantly inhibit
      the function of native CBF by recruiting transcriptional co-repressor complexes.
      However, knock-in studies have shown that whilst expression of these fusion genes
      may disrupt normal hematopoiesis, this, by itself, is not sufficient for the
      subsequent development of leukemia. Mutations of RUNX1 have been identified in
      familial platelet disorder (FDP), in which there is a congenital predisposition
      to the development of AML and heterozygous point mutations have been identified
      in the RUNX1 gene in some leukemias. Moreover, a small number of cases have been
      reported in which amplification of RUNX1 has been detected in childhood ALL
      suggesting mechanisms other than loss of function, such as gene dosage may also
      play a role. CONCLUSIONS: Understanding the role CBF plays in normal
      hematopoiesis and hematologic malignancies has provided critical reagents for the
      accurate identification of the broad group of leukemias harboring alterations of
      CBF. The application of these molecular approaches has already shown an impact on
      the clinical management of these patients and as more information becomes
      available, the ability to tailor therapy to improve each patient's chance of a
      cure becomes feasible.

PMID- 12495906
TI  - Dysregulated expression of Bcl-xL in CD34+ cells isolated from patients with
      refractory anemia with excess of blasts during megakaryocytic differentiation.

PMID- 12495905
TI  - DNA methylation and demethylating drugs in myelodysplastic syndromes and
      secondary leukemias.
AB  - BACKGROUND AND OBJECTIVES: Methylation of DNA is a common epigenetic modification
      that plays an important role in the control of gene expression in mammalian
      cells. This process involves CpG dinucleotide sequences and is catalyzed by DNA
      methyltransferase enzymes. Under physiological conditions, methylated CpG sites
      are only present in DNA sequences typical of bulk chromatin, where the DNA is
      inaccessible to transcription factors. In contrast, CpG islands of promoter
      regions are usually unmethylated (with few exceptions such as the genes on the
      inactive X-chromosome). DNA methylation abnormalities have recently emerged as
      the most frequent molecular changes in hematopoietic neoplasms. INFORMATION
      SOURCES: The authors of the present review are currently working in the field of
      myelodysplastic syndromes and secondary leukemias and have contributed original
      papers to peer-reviewed journals. The material analyzed in the present review
      includes articles and reviews published in journals covered by the Science
      Citation Index, and abstracts presented at recent international oncology and
      hematology meetings. STATE OF THE ART: Methylation and transcriptional status are
      inversely correlated, the hypermethylation of genes involved in cell-cycle
      control and apoptosis could have a pathogenetic role in the development of
      cancer. In particular, high-risk myelodysplastic syndromes (MDS) and secondary
      leukemias (SL) show a high prevalence of tumor-suppressor gene hypermethylation.
      The use of irreversible DNA methyltransferase inhibitors, such as 5-azacytidine
      and decitabine, appears to be a promising therapeutic option for the treatment of
      MDS and SL. Large clinical trials are still ongoing, but preliminary data
      recently published indicate for the first time that the natural history of MDS
      may be changed by a non-intensive treatment. CONCLUSIONS AND PERSPECTIVES:
      Treatment with demethylating agents, 5-azacytidine and decitabine, at present
      results in significantly higher response rates, improved quality of life, reduced
      risk of leukemic transformation, and improved survival, when compared to
      supportive care. Azacytidine and decitabine provide a new treatment option, and
      should be the treatment choice for elderly patients with high risk MDS. It is
      whorty in fact that azacytidine and decitabine are especially active in patients
      with poor prognosis MDS. The combination with histone deacetylase inhibitors may
      increase the efficacy of hypomethylating agents in vivo.

PMID- 12495907
TI  - Aggressive natural killer cell leukemia: clinical features and treatment outcome.

PMID- 12495908
TI  - STI571 (GLIVEC) induced hematologic, cytogenetic and molecular remission in a cml
      patient relapsing with accelerated phase after allogeneic stem cell
      transplantation.

PMID- 12495909
TI  - Combination of imatinib and established antileukemic treatment modalities for
      otherwise refractory BCR-ABL positive lymphoblastic leukemia.

PMID- 12495910
TI  - Fingertip cellulitis after fingerstick for capillary microhematocrit measurement
      in a patient with chronic lymphocytic leukemia: an uncommom infectious
      complication.

PMID- 12495911
TI  - Diffuse large B-cell lymphoma (DLBCL), anaplastic variant. report on a
      problematic case primarily arising in the stomach.

PMID- 12495912
TI  - Clinical and molecular remission following reduced intensity conditioning and
      allogeneic transplantation in a patient with refractory multiple myeloma.

PMID- 12495913
TI  - The prevention of the thalassemia maior: emergent problems.

PMID- 12495914
TI  - Primary cell wall composition of bryophytes and charophytes.
AB  - Major differences in primary cell wall (PCW) components between non-vascular
      plant taxa are reported. (1) Xyloglucan: driselase digestion yielded
      isoprimeverose (the diagnostic repeat unit of xyloglucan) from PCW-rich material
      of Anthoceros (a hornwort), mosses and both leafy and thalloid liverworts, as
      well as numerous vascular plants, showing xyloglucan to be a PCW component in all
      land plants tested. In contrast, charophycean green algae (Klebsormidium
      flaccidium, Coleochaete scutata and Chara corallina), thought to be closely
      related to land plants, did not contain xyloglucan. They did not yield
      isoprimeverose; additionally, charophyte material was not digestible with
      xyloglucan-specific endoglucanase or cellulase to give xyloglucan-derived
      oligosaccharides. (2) Uronic acids: acid hydrolysis of PCW-rich material from the
      charophytes, the hornwort, thalloid and leafy liverworts and a basal moss yielded
      higher concentrations of glucuronic acid than that from the remaining land plants
      including the less basal mosses and all vascular plants tested. Polysaccharides
      of the hornwort Anthoceros contained an unusual repeat-unit, glucuronic acid
      alpha(1-->3)-galactose, not found in appreciable amounts in any other plants
      tested. Galacturonic acid was consistently the most abundant PCW uronic acid, but
      was present in higher concentrations in acid hydrolysates of bryophytes and
      charophytes than in those of any of the vascular plants. Mannuronic acid was not
      detected in any of the species surveyed. (3) Mannose: acid hydrolysis of
      charophyte and bryophyte PCW-rich material also yielded appreciably higher
      concentrations of mannose than are found in vascular plant PCWs. (4) Mixed
      linkage glucan (MLG) was absent from all algae and bryophytes tested; however,
      upon digestion with licheninase, PCW-rich material from the alga Ulva lactuca and
      the leafy liverwort Lophocolea bidentata yielded penta- to decasaccharides,
      indicating the presence of MLG-related polysaccharides. Our results show that
      major evolutionary events are often associated with changes in PCW composition.
      In particular, the acquisition of xyloglucan may have been a pre-adaptive
      advantage that allowed colonization of land.

PMID- 12495915
TI  - Sexual differences in reproductive phenology and their consequences for the
      demography of Baccharis dracunculifolia (Asteraceae), a dioecious tropical shrub.
AB  - Patterns of phenological variation and reproductive investment were studied in
      the dioecious shrub Baccharis dracunculifolia DC (Asteraceae), and possible
      consequences on survivorship were evaluated. The sex ratio was determined in a
      natural field population (n = 921) of B. dracunculifolia in Belo Horizonte,
      Brazil. Fifty-two males and 56 females were sampled at random from this
      population. During the reproductive season of 1999, inflorescence production,
      shoot growth and mortality, and xylem water potential were recorded for each
      individual. The population sex ratio was male-biased (1.27 : 1, P < 0.05), and
      was associated with a higher mortality of female shoots (38.4 vs. 23.1 %, P <
      0.05), and individuals (17.8 vs. 11.5 %, P < 0.1), despite lower water stress in
      female plants. Flowering phenology also differed between the sexes, with males
      producing more inflorescences, and earlier, than females. Owing to fruit
      maturation, the number of inflorescences supported by females was higher than
      that supported by males later in the reproductive season. This occurred during
      the dry season, and drought stress may have been responsible for the greater
      female mortality. Thus, the male-biased sex ratio in this population of B.
      dracunculifolia is probably due to different reproductive functions of males and
      females. Intersexual differences in reproductive phenology had consequences for
      plant demography.

PMID- 12495916
TI  - Intraspecific variations in seedling emergence and survival of Potentilla
      matsumurae (Rosaceae) between alpine fellfield and snowbed habitats.
AB  - Potentilla matsumurae has a wide distribution from wind-blown fellfields to
      snowbeds in alpine regions of Japan. The environmental factors influencing
      seedling establishment differ between the fellfield and snowbed habitats; plants
      growing in each habitat may therefore have different germination strategies.
      Using a reciprocal sowing experiment, patterns of seedling emergence and
      survivorship were examined in both habitat types in the Taisetsu Mountains,
      Japan. Seeds derived from a fellfield population germinated earlier than did
      those derived from a snowbed population at both habitats, and the germination of
      fellfield seeds continued throughout the growing season. The timing of seedling
      emergence greatly affected subsequent survival at the fellfield. Seedlings that
      emerged in the first half of the growing season had low survivorship during the
      first year because of frost and drought damage, but the remaining seedlings had
      high survivorship during the winter; seedlings that emerged in the latter half of
      the growing season showed the opposite trend. At the snowbed, seedling survival
      was high throughout the growing season. Germination experiments in the laboratory
      highlighted a difference in the sensitivity of seeds from the fellfield and
      snowbed populations to fluctuating temperatures. These results indicate that
      intraspecific variation in emergence and survivorship may occur over a small
      scale in an alpine environment.

PMID- 12495917
TI  - First nuclear DNA C-values for 28 angiosperm genera.
AB  - This paper reports first DNA C-values for 28 angiosperm genera. These include
      first DNA C-values for 25 families, of which 16 are monocots. Overall familial
      representation is 47.2 % for angiosperms, but is now much higher for monocots (75
      %) and basal angiosperms (73.1 %) than for eudicots (38.7 %). Chromosome counts
      are reported for 22 taxa, including first records for six genera plus seven
      species. Unrepresented families will become increasingly enriched for monotypic
      taxa from obscure locations that are harder to access. Thus, completing familial
      representation for genome size for angiosperms may prove impossible in any short
      period, and progress towards this goal will become slower.

PMID- 12495918
TI  - Developmental patterns of the invasive bramble (Rubus alceifolius Poiret,
      Rosaceae) in Reunion island: an architectural and morphometric analysis.
AB  - The aim of this study was to identify the developmental stages of Rubus
      alceifolius and to determine one or more characteristic morphological markers for
      each stage. The developmental reconstitution method used involved a detailed
      description of many individuals throughout the different stages of growth, from
      germination to the development of an adult shoot capable of fruiting. Results
      revealed that R. alceifolius passes through five developmental stages that can be
      distinguished by changes in several morphological markers such as internode
      length and diameter, pith diameter and plant shape. This analysis indicated that
      R. alceifolius has a heteroblastic developmental pattern, midway between that of
      a bush and a liana. Moreover, results showed that this species taps environmental
      resources early in its development, i.e. foliarization is high (the foliar
      component overrides the caulinary component) and an autotrophic stage is rapidly
      reached, whereas it 'explores' the environment during the adult stage, i.e.
      axialization is substantial (the caulinary component overrides the foliar
      component) and autotrophy occurs at a later stage. The morphological markers
      identified could benefit land-use managers attempting to control this species
      before it reaches its optimum developmental stage.

PMID- 12495919
TI  - ITS sequence analysis and phylogenetic inference in the genus Lens mill.
AB  - The internal transcribed spacer (ITS) region of the nuclear ribosomal DNA from
      cultivated lentil (Lens culinaris subsp. culinaris) and its wild relatives was
      isolated and analysed for nucleotide sequence variation. Sequence divergence
      values ranged from no polymorphism within single species and between the cultigen
      and one accession of its wild progenitor (L. culinaris subsp. orientalis) to 14
      base substitutions between L. nigricans and L. lamottei. Jukes and Cantor
      distance ranged from 0 to 1.79 %. Phylogenetic analysis confirmed the divergence
      of L. nigricans from all species, and the closeness of cultivated lentil to its
      wild progenitor, although two gene pools could possibly be identified in subsp.
      orientalis. Based on this study, the two recently recognized species, L. lamottei
      and L. tomentosus were separated from the other species. Each wild species showed
      peculiar autapomorphies and, in general, did not display much variation among
      accessions. The trees using chickpea as an outgroup formed two main clusters, one
      constituted by L. nigricans only and the other including the remaining taxa.
      Within this larger group, small subclades could be identified.

PMID- 12495920
TI  - Branch architecture, light interception and crown development in saplings of a
      plagiotropically branching tropical tree, Polyalthia jenkinsii (Annonaceae).
AB  - To investigate crown development patterns, branch architecture, branch-level
      light interception, and leaf and branch dynamics were studied in saplings of a
      plagiotropically branching tree species, Polyalthia jenkinsii Hk. f. & Thoms.
      (Annonaceae) in a Malaysian rain forest. Lengths of branches and parts of the
      branches lacking leaves ('bare' branches) were smaller in upper branches than in
      lower branches within crowns, whereas lengths of 'leafy' parts and the number of
      leaves per branch were larger in intermediate than in upper and lower branches.
      Maximum diffuse light absorption (DLA) of individual leaves was not related to
      sapling height or branch position within crowns, whereas minimum DLA was lower in
      tall saplings. Accordingly, branch-level light interception was higher in
      intermediate than in upper and lower branches. The leaf production rate was
      higher and leaf loss rate was smaller in upper than in intermediate and lower
      branches. Moreover, the branch production rate of new first-order branches was
      larger in the upper crowns. Thus, leaf and branch dynamics do not correspond to
      branch-level light interception in the different canopy zones. As a result of
      architectural constraints, branches at different vertical positions experience
      predictable light microenvironments in plagiotropic species. Accordingly, this
      pattern of carbon allocation among branches might be particularly important for
      growth and crown development in plagiotropic species.

PMID- 12495921
TI  - Suitability of cryopreservation for the long-term storage of rare and endangered
      plant species: a case history for Cosmos atrosanguineus.
AB  - The suitability of cryopreservation for the secure, long-term storage of the rare
      and endangered species Cosmos atrosanguineus was investigated. Using
      encapsulation/dehydration of shoot tips in alginate strips, survival rates of up
      to 100 % and shoot regeneration of up to 35 % were achieved. Light and electron
      microscopy studies indicated that cellular damage to some regions of the shoot
      tip during the freeze/thaw procedure was high, although cell survival in and
      around the meristematic region allowed shoot tip regeneration. The genetic
      fingerprinting technique, amplified fragment length polymorphisms (AFLPs), showed
      that no detectable genetic variation was present between material of C.
      atrosanguineus at the time of initiation into tissue culture and that which had
      been cryopreserved, stored in liquid nitrogen for 12 months and regenerated.
      Weaned plantlets that were grown under glasshouse conditions exhibited no
      morphological variation from non-frozen controls.

PMID- 12495922
TI  - Survival of Ranunculus repens L. (creeping buttercup) in an amphibious habitat.
AB  - The turlough form of Ranunculus repens is subjected to several months' complete
      inundation with hard groundwater. Experimental flooding to the level of the soil
      surface had no effect on turlough or ruderal populations relative to drained
      controls. Experimental submergence resulted in direct tissue death of the ruderal
      population but did not affect the turlough population relative to drained
      controls. There was no detectable difference in the proportion of aerenchyma in
      drained, flooded and submerged roots of plants from either population. The
      proportion of aerenchyma increased with root age in the ruderal population. Up to
      twice the proportion of aerenchyma occurred in the lower third of the root in the
      turlough population relative to the middle and upper thirds. Submergence in
      artificially hardened tap water increased the amount of tissue death in the
      ruderal population, whereas it appeared to enhance the growth of plants from the
      turlough population relative to that of plants submerged in tap water. Only the
      ruderal population demonstrated a depth accommodation response in submerged
      conditions. Root concentrations of ethanol-soluble carbohydrates were up to three
      times higher in a field- collected turlough population during winter and autumn
      months than those in a ruderal population. Low levels of ethanol-insoluble
      carbohydrates were present in the turlough population but were absent from the
      ruderal population. Starch concentrations fluctuated greatly in the turlough
      population and were generally higher than those in the ruderal population. These
      results, together with those from previous investigations, suggest that the
      turlough population survives prolonged submergence by maintaining low levels of
      submerged photosynthesis, which may circulate oxygen within the plant tissues,
      and by utilizing storage carbohydrates for maintenance respiration.

PMID- 12495923
TI  - Evidence that carbon dioxide enrichment alleviates ureide-induced decline of
      nodule nitrogenase activity.
AB  - The hypothesis that elevated [CO(2)] alleviates ureide inhibition of N(2)
      fixation was tested. Short-term responses of the acetylene reduction assay (ARA),
      ureide accumulation and total non-structural carbohydrate (TNC) levels were
      measured following addition of ureide to the nutrient solution of hydroponically
      grown soybean. The plants were exposed to ambient (360 micromol mol(-1)) or
      elevated (700 micromol mol(-1)) [CO(2)]. Addition of 5 and 10 mM ureide to the
      nutrient solution inhibited N(2)-fixation activity under both ambient and
      elevated [CO(2)] conditions. However, the percentage inhibition following ureide
      treatment was significantly greater under ambient [CO(2)] as compared with that
      under elevated [CO(2)]. Under ambient [CO(2)] conditions, ARA was less than that
      under elevated [CO(2)] 1 d after ureide treatment. Under ambient [CO(2)], the
      application of ureide resulted in a significant accumulation of ureide in all
      plant tissues, with the highest concentration increases in the leaves. However,
      application of exogenous ureide to plants subjected to elevated [CO(2)] did not
      result in increased ureide concentration in any tissues. TNC concentrations were
      consistently higher under elevated [CO(2)] compared with those under ambient
      [CO(2)]. For both [CO(2)] treatments, the application of ureide induced a
      significant decrease of TNC concentrations in the leaves and nodules. For both
      leaves and nodules, a negative correlation was observed between TNC and ureide
      levels. Results indicate that product(s) of ureide catabolism rather than tissue
      ureide concentration itself are critical in the regulation of N(2)-fixation.

PMID- 12495924
TI  - Exploring within-tree architectural development of two apple tree cultivars over
      6 years.
AB  - The present study addresses the prediction of apple tree development, taking into
      account both the number and within-tree position of tree components. The
      architectural development of two trees per scion cultivar, 'Fuji' and 'Braeburn',
      was studied by describing all shoots over 6 years. Flowering and fruiting were
      observed over 3 years. The description included different scales [entire trees,
      axes, growth units (GUs) and metamers], and the analysis compared all axes of the
      trees as a function of their branching order and age. Three main aspects of
      vegetative development were investigated: the quantity of primary growth; the
      number and nature of developing axillary shoots; and meristem death. Results
      confirm the existence of within-tree morphological gradients, and show that the
      decrease in growth was comparable in magnitude for all axes and GUs, irrespective
      of their position. This decrease results from a reduction in the number of
      metamers per GU, which was modelled by an exponential function. The decrease in
      growth involved changes in the number and nature of the axillary shoots, which
      could be described by simple functions. The probability of spur death was
      constant over the years but differed according to cultivar and type of bearing
      shoot. The within-tree probability of flowering and fruiting was predictable for
      'Braeburn' because axes, regardless of their position and type, had a high
      probability of flowering and a low probability of fruit set which led to a
      regular bearing habit. In contrast, 'Fuji' had an alternating bearing behaviour
      that was more complex to predict. This appeared to result from a synchronized
      increase in the probability that all GUs at tree scale are floral, combined with
      a high probability of fruit set. The consequences of these results for both yield
      prediction and architectural simulations are discussed.

PMID- 12495925
TI  - Of mice and men.

PMID- 12495926
TI  - Midkine: a potential bridge between glucocorticoid and retinoid effects on lung
      vascular development.

PMID- 12495927
TI  - Interleukin-17: an emerging role in lung inflammation.

PMID- 12495928
TI  - Matrix metalloproteinase-9 in lung remodeling.
AB  - Matrix metalloproteinase (MMP)-9 (Gelatinase B, 92-kD type IV collagenase, EC
      3.4.24.35) is an MMP that is present in low quantities in the healthy adult lung,
      but much more abundant in several lung diseases, including asthma, idiopathic
      pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD).
      Despite numerous reports of MMP-9 in these and other lung diseases, whether MMP-9
      is causal in lung remodeling or part of the inflammatory and reparative response
      remains to be determined. Many intrinsic lung cells can be stimulated to produce
      MMP-9, but much of the information regarding MMP-9 in the lung deals with MMP-9
      from inflammatory cells. The multiple locations and cell types producing MMP-9
      are consistent with multiple functions in different microenvironments. In
      addition to digestion of structural proteins and antiproteases, MMP-9 can modify
      cellular function by regulation of cytokines and matrix-bound growth factors.
      Determining the role of MMP-9 in health and disease will be important, because
      broad spectrum and specific inhibitors will soon be available to enable
      conversion of the bench knowledge to bedside practice. This review addresses the
      current understanding of MMP-9 in human asthma, IPF, and COPD, and in animal
      models of these conditions.

PMID- 12495929
TI  - Involvement of the cysteinyl-leukotrienes in allergen-induced airway eosinophilia
      and hyperresponsiveness in the mouse.
AB  - The leukotriene modifiers are a novel generation of therapeutic agents in the
      treatment of allergic asthma. However, the mechanisms by which the cysteinyl
      (cys) leukotrienes (LTs) participate in allergen-induced airway eosinophilia and
      airway hyperresponsiveness (AHR) are still unclear. In the present study, we have
      investigated the role of cys-LTs in ovalbumin (OVA)-induced airway responses in a
      murine model of asthma. Montelukast (3 or 10 mg/kg), a selective cys-LT1 receptor
      antagonist, reduced airway eosinophilia and AHR after OVA challenge. The levels
      of interleukin (IL)-5 and eotaxin in the bronchoalveolar lavage fluid (BALF) from
      montelukast-treated (3 mg/kg) mice were unaffected, although a decrease in IL-5
      was observed with a dose of 10 mg/kg. LTD4 (50 ng) instilled intranasally to
      immunized mice augmented macrophages in the BALF, but in conjunction with OVA
      challenge it caused BALF eosinophilia and neutrophilia when given before
      challenge and BALF neutrophilia but not eosinophilia when given 2 h after
      challenge. However, there were no increases of IL-5 or eotaxin in BALF following
      LTD4 treatment. Repeated instillations of LTD4 to immunized mice, mimicking
      allergen challenge, did not induce AHR but in conjunction with OVA challenge LTD4
      enhanced AHR. These results indicate that allergen-induced eosinophilia and AHR
      are in part mediated by the cys-LT1 receptor, and that, although LTD4 alone has
      no effect on airway eosinophilia, in conjunction with antigenic stimulation it
      potentiates the degree of airway inflammation and AHR.

PMID- 12495930
TI  - The growth factor midkine is modulated by both glucocorticoid and retinoid in
      fetal lung development.
AB  - The glucocorticoids (GC) and retinoids (RA) modulate branching morphogenesis and
      cytodifferentiation in the developing lung. We investigated downstream target
      genes that link glucocorticoid stimulation to the achievement of a mature lung in
      glucocorticoid receptor (GR) knockout mice. All GR(null) mice and approximately
      80% of mice homozygous for a hypomorphic allele (GR(hypo)) die shortly after
      birth of respiratory failure. cDNA microarray analysis showed organ-specific
      upregulation of the retinoic acid responsive gene midkine (MK) and its
      chondroitin-sulfate binding partner PG-M/versican at fetal day 18 and at neonatal
      day 1 in lungs of GR(hypo) mice, and at neonatal day 1 in lungs of GR(null) mice.
      By contrast, lung MK and PG-M/versican were downregulated in these mice at fetal
      day 16.5. In situ hybridization studies showed a dramatic decrease in MK and PG
      M/versican RNA between days 16.5 and 17.5 in GR(WT) but not in GR(null) mice.
      Continued diffuse and robust expression of MK protein was observed in GR(null)
      mice at neonatal day 1. These findings suggest that MK may contribute to the
      dysmature lung phenotype in GR-deficient mice. Exposure of cultured day 21 fetal
      rat lung cells to GC downregulated MK, whereas RA enhanced MK expression. Our
      findings demonstrate the coincident modulation of expression of MK at the same
      developmental time point by both GC and RA, providing a potential mechanism for
      the integration of GC and RA effects on fetal lung development.

PMID- 12495931
TI  - Interleukin-17 orchestrates the granulocyte influx into airways after allergen
      inhalation in a mouse model of allergic asthma.
AB  - Interleukin (IL)-17 is produced by activated memory CD4(+) cells and induces
      cytokines and chemokines that stimulate neutrophil generation and recruitment.
      Here, we investigated the involvement of IL-17 in the bronchial influx of
      neutrophils in experimental allergic asthma. Inhalation of nebulized ovalbumin
      (OVA) by sensitized mice with bronchial eosinophilic inflammation resulting from
      chronic OVA exposure induced early IL-17 mRNA expression in inflamed lung tissue,
      concomitant with a prominent bronchial neutrophilic influx. Anti-IL-17 monoclonal
      antibodies (mAb) injected before allergen inhalation strongly reduced bronchial
      neutrophilic influx, in a manner equally as potent as the anti-inflammatory
      dexamethasone. Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in
      both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia.
      In another series of experiments, anti-IL-17 mAb were given repeatedly during the
      inhalatory challenge phase with OVA of sensitized mice. This treatment regimen
      abated bronchial neutrophilia in parallel with reduction of bone marrow and blood
      neutrophilia. In addition, anti-IL-17 mAb treatment elevated eosinophil counts in
      the bone marrow and bronchial IL-5 production, without alteration of allergen
      induced bronchial hyperresponsiveness. In summary, our results demonstrate that
      IL-17 expression in airways is upregulated upon allergen inhalation, and
      constitutes the link between allergen-induced T cell activation and neutrophilic
      influx. Because neutrophils may be important in airway remodeling in chronic
      severe asthma, targeting IL-17 may hold therapeutic potential in human asthma.

PMID- 12495932
TI  - Asbestos inhalation induces tyrosine nitration associated with extracellular
      signal-regulated kinase 1/2 activation in the rat lung.
AB  - Nitration of proteins by peroxynitrite (ONOO-) has been shown to critically alter
      protein function in vitro. We have shown previously that asbestos inhalation
      induced nitrotyrosine formation, a marker of ONOO- production, in the rat lung.
      To determine whether asbestos-induced protein nitration may affect mitogen
      activated protein kinase (MAPK) signaling pathways, lung lysates from crocidolite
      and chrysotile asbestos-exposed rats and from sham-exposed rats were
      immunoprecipitated with anti-nitrotyrosine antibody, and captured proteins were
      subjected to Western blotting with anti-phospho-extracellular signal-regulated
      kinase (ERK)1/2 antibodies. Both types of asbestos inhalation induced
      significantly greater phosphorylation of ERK1/2 in rat lung lysates than was
      noted after sham exposure. Phosphorylated ERK proteins co-immunoprecipitated with
      nitrotyrosine. Moreover, in MAPK functional assays using Elk-1 substrate,
      immunoprecipitated phospho-ERK1/2 in lung lysates from both crocidolite-exposed
      and chrysotile-exposed rats demonstrated significantly greater phosphorylation of
      Elk-1 than was noted after sham exposure. Asbestos inhalation also induced ERK
      phosphorylation in bronchoalveolar lavage cells. Lung sections from rats exposed
      to crocidolite or chrysotile (but not from sham-exposed rats nor from rats
      exposed to "inert" carbonyl iron particles) demonstrated strong immunoreactivity
      for nitrotyrosine and phospho-ERK1/2 in alveolar macrophages and bronchiolar
      epithelium. These findings suggest that asbestos fibers may activate the ERK
      signaling pathway by generating ONOO- or other nitrating species that induce
      tyrosine nitration and phosphorylation of critical signaling molecules.

PMID- 12495933
TI  - Increased expression of p21(waf) cyclin-dependent kinase inhibitor in asthmatic
      bronchial epithelium.
AB  - Because the asthmatic bronchial epithelium is characterized by widespread damage,
      we postulated that this is associated with expression of cell cycle inhibitors
      that control proliferation. Using bronchial biopsies, the epithelium was the
      major site of expression of the cyclin-dependent kinase inhibitor, p21(waf).
      Immunostaining usually occurred in the cytoplasm of columnar cells; however, in
      severe asthma, nuclear staining was also evident in the proliferative, basal cell
      compartment. p21(waf) expression was significantly higher in asthmatic versus
      nonasthmatic epithelium and was unaffected by corticosteroid treatment;
      proliferating cell nuclear antigen was not significantly different in any group.
      p21(waf), but not p27(kip1), mRNA and protein were induced by treatment of
      bronchial epithelial cells in vitro with transforming growth factor (TGF)-beta or
      H2O2, but not by dexamethasone, which induced p57(kip2). TGF-beta and
      dexamethasone inhibited epidermal growth factor (EGF)-induced DNA synthesis,
      whereas low concentrations of H2O2 synergized with EGF; at higher doses, growth
      inhibition and induction of apoptosis occurred. TGF-beta caused p21(waf) to
      become nuclear, suggesting interaction with the replicative machinery; however,
      in oxidant-stressed cells, p21(waf) was predominantly cytoplasmic, where it has
      been linked to cell survival. We conclude that p21(waf) overexpression in asthma
      influences cell proliferation and survival. This may cause abnormal repair
      responses that contribute to airway inflammation and remodeling.

PMID- 12495934
TI  - Cysteine protease activity is required for surfactant protein B processing and
      lamellar body genesis.
AB  - Surfactant protein (SP)-B is essential for lamellar body genesis and for the
      final steps in proSP-C post-translational processing. The mature SP-B protein is
      derived from multistep processing of the primary translation product proSP-B;
      however, the enzymes required for these events are currently unknown. Recent
      ultrastructural colocalization studies have suggested that the cysteine protease
      Cathepsin H may be involved in proSP-B processing. Using models of isolated human
      type 2 cells in culture, we describe the effects of cysteine protease inhibition
      by E-64 on SP-B processing and type 2 cell differentiation. Pulse-chase labeling
      and Western immunoblotting studies showed that the final step of SP-B processing,
      specifically cleavage of SP-B(9) to SP-B(8), was significantly inhibited by E-64,
      resulting in delayed accumulation of SP-B(8) without adverse effects on SP-A or
      glyceraldehyde phosphate dehydrogenase expression. E-64 treatment during type 2
      cell differentiation mimicked features of inherited SP-B deficiency in humans and
      mice, specifically disrupted lamellar body genesis, and aberrant processing of
      proSP-C. Reverse transcriptase-polymerase chain reaction and Western
      immunoblotting studies showed that Cathepsin H is induced during in vitro
      differentiation of type 2 cells and localizes with SP-B in multivesicular bodies,
      composite bodies, and lamellar bodies by immunoelectron microscopy. Furthermore,
      Cathepsin H activity was specifically inhibited in a dose-dependent fashion by E
      64. Our data show that a cysteine protease is involved in SP-B processing,
      lamellar body genesis, and SP-C processing, and suggest that Cathepsin H is the
      most likely candidate protease.

PMID- 12495935
TI  - Downregulation of hnRNP A2/B1 expression in tumor cells under prolonged hypoxia.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been previously shown
      to be overexpressed in breast and lung tumors. Because hypoxia is a feature
      inherent in solid tumors, the regulation of hnRNP A2/B1 expression and
      subcellular localization under hypoxic conditions was studied on human lung and
      breast carcinoma cell lines. We found that sustained hypoxic treatment
      downregulated hnRNP A2/B1 expression in MCF7 and H157 cell lines. Northern blot
      analysis showed that this decay: (i) was observed as a marked diminution of
      transcript levels after 24-48 h of exposure to low oxygen tension; (ii) is not
      mediated by the transcription factor, hypoxia inducible factor-1; and (iii) is
      partially dependent on a higher hnRNP A2/B1 messenger RNA turnover under hypoxic
      than normoxic conditions. Immunocytochemical staining also showed a significant
      diminution of hnRNP A2/B1 staining in these cell lines after 24-48 h of hypoxia,
      together with a predominant loss of cytoplasmic staining. Further investigations
      are warranted to evaluate the relevance of modulation of hnRNP A2/B1 in hypoxic
      environments relative to its previously reported utility as a marker of early
      lung carcinogenesis.

PMID- 12495936
TI  - Downregulation of the epidermal growth factor receptor by human cytomegalovirus
      infection in human fetal lung fibroblasts.
AB  - Epidermal growth factor plays a key role in late fetal lung development and
      differentiation as well as in regulating surfactant protein A synthesis, which is
      involved in innate immunity of the lung. Here we show that human cytomegalovirus
      (HCMV), a known lung pathogen in connatal and postnatal infection of neonates as
      well as transplant recipients, completely down-regulates EGF receptor (EGF-R) on
      the surface of human fetal lung fibroblasts. Inhibition of EGF-R synthesis occurs
      on the transcriptional rather than on the posttranscriptional level. The effect
      essentially depends on expression of viral immediate early and/or early genes, as
      binding of ultraviolet light-inactivated virus to the cells had no effect on EGF
      R expression. Furthermore, the anti-HCMV drug ganciclovir, which blocks HCMV DNA
      replication and late gene expression, cannot overcome HCMV-mediated inhibition of
      EGF-R, suggesting that immediate early or early gene products may be responsible
      for down-regulation of EGF-R. Interestingly, the glucocorticoid dexamethasone,
      which is used for its antiinflammatory action to prevent chronic lung disease in
      preterm infants, promotes HCMV-associated downregulation of the EGF-R by
      stimulation of viral gene expression. From these data it can be hypothesized that
      the pathogenesis of HCMV lung infection involves down-regulation of EGF-R and
      that congenital HCMV infection may cause retardation in lung maturation and
      surfactant protein synthesis.

PMID- 12495937
TI  - Selective inhibition of large-to-small surfactant aggregate conversion by serine
      protease inhibitors of the bis-benzamidine type.
AB  - Conversion of the biophysically active large surfactant aggregate subtype (LA) of
      alveolar surfactant into the less surface active small surfactant aggregates (SA)
      occurs in vivo and is reproduced under conditions of cyclic surface area changes
      in vitro. A serine-active carboxyl esterase has been suggested as the responsible
      enzymatic activity, although the exact mechanisms underlying the conversion
      process are presently unclear. We investigated the influence of exogenous serine
      proteases and synthetic and natural serine protease inhibitors on the conversion
      kinetics of natural rabbit surfactant, obtained as bronchoalveolar lavage fluid
      (BALF). In vitro cycling of BALF was performed for various time periods in the
      absence or presence of increasing amounts of several serine proteases (trypsin,
      plasmin, thrombin, tryptase), and one natural (aprotinin) and 25 synthetic serine
      protease inhibitors (including regular benzamidines [group A], 3
      amidinophenylalanine derivatives [group B], bis-benzamidines [group C], and
      analogs of naphthylsulfonyl-glycyl-4-amidinophenylalanine piperidide [group D]).
      LA were separated from SA by 48,000 x g centrifugation. Surface activity of the
      LA fraction was measured by means of the pulsating bubble surfactometer. None of
      the "classical" serine proteases forwarded any acceleration of the LA-to-SA
      conversion kinetics. Some of the serine protease inhibitors caused moderate
      retardation of conversion, but at the same dose range inhibited the surface
      tension-lowering properties of the LA fraction, which per se explained their
      inhibitory effect. In contrast, specific dose-dependent inhibition of the LA-to
      SA transition was observed for four derivatives of the bis-benzamidine group:
      full blockage of conversion over 240 min of cycling was noted at doses that did
      not interfere with the surface activity of the LA fraction. In addition, the
      prototype of these bis-benzamidines, 1,4-bis-[beta-naphthylsulfonyl-(3
      aminophenylalanine)]-piperazide, was found to inhibit the activity of the rabbit
      liver carboxylesterase ES-2 in two different synthetic substrate assays
      reflecting the amidase and esterase properties of carboxylesterases. These
      findings support the hypothesis that the LA-to-SA conversion is an enzymatically
      driven process with serine-active carboxyl esterase(s) being centrally involved.
      Synthetic bis-benzamidine-type serine protease inhibitors may offer specific
      inhibition of this event.

PMID- 12495938
TI  - Airway smooth muscle cells express functional neurokinin-1 receptors and the
      nerve-derived preprotachykinin-a gene: regulation by passive sensitization.
AB  - Preprotachykinin-A (PPT-A) gene-derived neuropeptides, namely substance P (SP)
      and neurokinin (NK)A, and their receptors participate in allergen-induced airway
      responses. Whether airway smooth muscle cells (ASMC) may react directly to SP
      through expression of the NK-1 receptor or express the gene for the synthesis of
      SP, the PPT-A gene, is unknown. We demonstrated using reverse transcription
      polymerase chain reaction that tracheal SMC (TSMC) from atopic Brown Norway rats
      contained mRNA transcripts for the full-length isoform of the NK-1 receptor. Flow
      cytometric analysis indicated that the NK-1 receptor was expressed on the surface
      of TSMC. This receptor was functional as demonstrated by calcium mobilization in
      response to SP stimulation. The expression of the NK-1 receptor was not altered
      in passively sensitized TSMC in response to antigenic stimulation, although this
      stimulation increased the expression of the chemokine RANTES (regulated on
      activation, normal T cells expressed and secreted). Using different sets of PCR
      primers, we showed that TSMC also express the beta, alpha, and its alternative
      splicing product delta, and possibly the gamma mRNA transcript isoforms of the
      PPT-A gene. Gene sequencing of the PCR-amplified beta isoform confirmed that it
      is a transcript product of the rat PPT-A gene, and the production of SP by TSMC
      was confirmed by enzyme immunoassay. We also showed the beta isoform increased
      after cell stimulation with rat sera, whether sensitized or not. In conclusion,
      both the PPT-A gene and NK-1 receptors are expressed by TSMC, which suggests the
      possibility of autocrine neuropeptidergic mechanisms in these cells. However,
      these mechanisms are not upregulated by passive sensitization.

PMID- 12495939
TI  - Ultrafine carbon black particles inhibit human lung fibroblast-mediated collagen
      gel contraction.
AB  - Both acute and chronic exposure to particulates have been associated with
      increased mortality and morbidity from a number of causes, including chronic
      obstructive pulmonary disease and other chronic lung diseases. The current study
      evaluated the hypothesis that ultrafine carbon particles, a component of ambient
      particulates, could affect tissue repair. To assess this, the three-dimensional
      collagen gel contraction model was used. Ultrafine carbon black particles, but
      not fine carbon black, inhibited fibroblast-mediated collagen gel contraction.
      Although previous research has indicated that inflammatory effects of ultrafine
      carbon black particles are mediated by oxidant mechanisms, the current study
      suggests that ultrafine carbon black's inhibition of fibroblast gel contraction
      is mediated by the binding of both fibronectin and transforming growth factor
      (TGF)-beta to the ultrafine particles. Binding of TGF-beta was associated with a
      reduction in nuclear localization of Smads, indicative of inhibition of TGF-beta
      signal transduction. There was also a decrease in fibronectin mRNA, consistent
      with a decrease in TGF-beta-mediated response. Taken together, these results
      demonstrate the ability of ultrafine particles to contribute to altered tissue
      repair and extend the known mechanisms by which these biologically active
      particles exert their effects.

PMID- 12495940
TI  - Microarray analysis of lipopolysaccharide-treated human neutrophils.
AB  - Neutrophils respond to infection by degranulation, release of reactive oxygen
      intermediates, and secretion of chemokines and cytokines; however, activation of
      neutrophil transcriptional machinery has been little appreciated. Recent findings
      suggest that gene expression may represent an additional neutrophil function
      after exposure to lipopolysaccharide (LPS). We performed microarray gene
      expression analysis of 4,608 mostly nonredundant genes on LPS-stimulated human
      neutrophils. Analysis of three donors indicated some variability but also a high
      degree of reproducibility in gene expression. Twenty-eight verifiable, distinct
      genes were induced by 4 h of LPS treatment, and 13 genes were repressed. Genes
      other than cytokines and chemokines are regulated; interestingly, genes involved
      in cell growth regulation and survival, transcriptional regulation, and
      interferon response are among those induced, whereas genes involved in
      cytoskeletal regulation are predominantly repressed. In addition, we identified
      monocyte chemoattractant protein-1 as a novel LPS-regulated chemokine in
      neutrophils. Included in these lists are five clones with no defined function.
      These data suggest molecular mechanisms by which neutrophils respond to infection
      and indicate that the transcriptional potential of neutrophils is greater than
      previously thought.

PMID- 12495941
TI  - Involvement of protein tyrosine kinase in Toll-like receptor 4-mediated NF-kappa
      B activation in human peripheral blood monocytes.
AB  - Bacterial lipopolysaccharide (LPS) is a powerful activator of the innate immune
      system. Exposure to LPS induces an inflammatory reaction in the lung mediated
      primarily by human blood monocytes and alveolar macrophages, which release an
      array of inflammatory chemokines and cytokines including IL-8, TNF-alpha, IL
      1beta, and IL-6. The signaling mechanisms utilized by LPS to stimulate the
      release of cytokines and chemokines are still incompletely understood.
      Pretreatment with the protein tyrosine kinase-specific inhibitors genistein and
      herbimycin A effectively blocked LPS-induced NF-kappaB activation as well as IL-8
      gene expression in human peripheral blood monocytes. However, when genistein was
      added 2 min after the addition of LPS, no inhibition was observed. Utilizing a
      coimmunoprecipitation assay, we further showed that LPS-stimulated tyrosine
      phosphorylation of Toll-like receptor 4 (TLR4) may be involved in downstream
      signaling events induced by LPS. These findings provide evidence that LPS-induced
      NF-kappaB activation and IL-8 gene expression use a signaling pathway requiring
      protein tyrosine kinase and that such regulation may occur through tyrosine
      phosphorylation of TLR4.

PMID- 12495942
TI  - Neutrophil elastase increases MUC4 expression in normal human bronchial
      epithelial cells.
AB  - In chronic obstructive pulmonary diseases, the airway epithelium is chronically
      exposed to neutrophil elastase, an inflammatory protease. The cellular response
      to neutrophil elastase dictates the balance between epithelial injury and repair.
      Key regulators of epithelial migration and proliferation are the ErbB receptor
      tyrosine kinases, including the epidermal growth factor receptor. In this
      context, we investigated whether neutrophil elastase may regulate expression of
      MUC4, a membrane-tethered mucin that has recently been identified as a ligand for
      ErbB2, the major heterodimerization partner of the epidermal growth factor
      receptor. In normal human bronchial epithelial cells, neutrophil elastase
      increased MUC4 mRNA levels in both a concentration- and time-dependent manner.
      RNA stability assays revealed that neutrophil elastase increased MUC4 mRNA levels
      by prolonging the mRNA half-life from 5 to 21 h. Neutrophil elastase also
      increased MUC4 glycoprotein levels as determined by Western analysis, using a
      monoclonal antibody specific for a nontandem repeat MUC4 sequence. Therefore,
      airway epithelial cells respond to neutrophil elastase exposure by increasing
      expression of MUC4, a potential activator of epithelial repair mechanisms.

PMID- 12495943
TI  - Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of
      Niemann-Pick disease.
AB  - Types A and B Niemann-Pick disease (NPD) are lipid storage disorders caused by
      the deficient activity of acid sphingomyelinase (ASM). In humans, NPD is
      associated with the dysfunction of numerous organs including the lung. Gene
      targeting of the ASM gene in transgenic mice produced an animal model with
      features typical of NPD, including pulmonary inflammation. To assess mechanisms
      by which ASM perturbed lung function, we studied lung morphology, surfactant
      content, and metabolism in ASM-deficient mice in vivo. Pulmonary inflammation,
      with increased cellular infiltrates and the accumulation of alveolar material,
      was associated with alterations in surfactant content. Saturated
      phosphatidylcholine (SatPC) content was increased twofold, and sphingomyelin
      content was increased 5.5-fold in lungs of the ASM knockout (ASMKO) mice.
      Additional sphingomyelin enhanced the sensitivity of surfactant inhibition by
      plasma proteins. Clearance of SatPC from the lungs of ASMKO mice was decreased.
      Catabolism of SatPC by alveolar macrophages from the ASMKO mouse was
      significantly decreased, likely accounting for decreased pulmonary SatPC in vivo.
      In summary, ASM is required for normal surfactant catabolism by alveolar
      macrophages in vivo. Alterations in surfactant composition, including increased
      sphingomyelin content, contributed to the abnormal surfactant function observed
      in the ASM-deficient mouse.

PMID- 12495944
TI  - Health protection and a new strategy for combating infection in children.

PMID- 12495945
TI  - Forty years of the Paediatric Research Society in the United Kingdom.

PMID- 12495946
TI  - Cold light transillumination as an aid to umbilical catheterisation.

PMID- 12495947
TI  - Doctor, who will be looking after my child's diabetes?

PMID- 12495948
TI  - Randomised controlled trial of site specific advice on school travel patterns.
AB  - AIMS: To evaluate the effect of site specific advice from a school travel
      coordinator on school travel patterns. METHODS: Cluster randomised controlled
      trial of children attending 21 primary schools in the London boroughs of Camden
      and Islington. A post-intervention survey measured the proportion of children
      walking, cycling, or using public transport for travel to school, and the
      proportion of parents/carers very or quite worried about traffic and abduction.
      The proportion of schools that developed and implemented travel plans was
      assessed. RESULTS: One year post-intervention, nine of 11 intervention schools
      and none of 10 control schools had travel plans. Proportions of children walking,
      cycling, or using public transport on the school journey were similar in
      intervention and control schools. The proportion of parents who were very or
      quite worried about traffic danger was similar in the intervention (85%) and
      control groups (87%). However, after adjusting for baseline and other potential
      confounding factors we could not exclude the possibility of a modest reduction in
      parental concern about traffic danger as a result of the intervention.
      CONCLUSIONS: Having a school travel coordinator increased the production of
      school travel plans but there was no evidence that this changed travel patterns
      or reduced parental fears. Given the uncertainty about effectiveness, the policy
      of providing school travel coordinators should only be implemented within the
      context of a randomised controlled trial.

PMID- 12495950
TI  - Stop tuberculosis!

PMID- 12495949
TI  - Low back pain in schoolchildren: the role of mechanical and psychosocial factors.
AB  - BACKGROUND: Low back pain (LBP) in schoolchildren with no apparent clinical cause
      is known to be a common problem, but considerably less is understood regarding
      the aetiology of such pain. AIM: To assess the role of both mechanical and
      psychosocial factors (including emotional and behavioural problems and other
      somatic pain complaints) in childhood LBP. METHODS: A cross sectional study was
      carried out in a population of 1446 schoolchildren aged 11-14 years. Information
      on these potential risk factors for LBP was sought using a self complete
      questionnaire and a five day bag weight diary. RESULTS: Mechanical factors such
      as physical activity and school bag weight were not associated with LBP. However,
      strong associations with LBP were observed for emotional problems, conduct
      problems, troublesome headaches, abdominal pain, sore throats, and daytime
      tiredness. CONCLUSION: Results suggest that psychosocial factors rather than
      mechanical factors are more important in LBP occurring in young populations and
      could possibly be a reflection of distress in schoolchildren.

PMID- 12495951
TI  - Parental knowledge of school backpack weight and contents.
AB  - Parental knowledge of their students' backpack weight and contents was assessed
      by identifying 188 students who carried backpacks weighing at least 10% of their
      body weights through a survey of 745 students in three elementary schools. Most
      parents (96%) had never checked their child's backpack weight; 34% had never
      checked the backpack contents.

PMID- 12495952
TI  - Six month impact of false positives in an Australian infant hearing screening
      programme.
AB  - AIMS: To assess short and longer term parent reported impacts of false positive
      referrals in the Victorian Infant Hearing Screening Program (VIHSP). METHODS:
      Mailed retrospective case-control survey of infants consecutively referred to
      VIHSP between December 1998 and April 1999 for whom audiology did not confirm
      permanent hearing loss, comprising 137 infants screened with a neonatal risk
      factor questionnaire and 148 older infants screened with two consecutive
      behavioural (distraction) tests. The two control groups comprised non-referred
      screened infants matched by domicile, age, and gender. Main outcome measures were
      parent reported emotions experienced before and after child's audiology test,
      parent estimated impact of hearing loss, the Child Vulnerability Scale, audiology
      assessment satisfaction questionnaire, and questions relating to their child's
      hearing and language development. RESULTS: Final sample: at risk cases (AR) 108
      (79% response), at risk controls 64 (51%); distraction test cases (DT) 103 (70%),
      distraction test controls 53 (41%). Parents across all groups believed that
      hearing loss would have major effects on a child's language (91-96%), schooling
      (81-91%), and employment opportunities (67-75%). Before audiology, 71% (AR) and
      72% (DT) of case parents were anxious/worried, falling to 4% and 15% afterwards.
      After the test 82% (AR) and 79% (DT) reported relief, but 19% and 18% continued
      to feel worried. Ongoing concerns about hearing, language, development, and
      general health were comparable for AR cases compared to controls, and for DT
      cases compared to controls. CONCLUSIONS: Hearing screening tests are generally
      well received. Parents are realistic about the impact of childhood hearing loss
      and report a range of negative emotions when a false positive hearing screen
      requires referral. Although most are reassured by a normal test, a substantial
      number report continuing concern.

PMID- 12495953
TI  - Choosing deafness.

PMID- 12495954
TI  - Screening and follow up assessment in three cases of auditory neuropathy.
AB  - Three children with auditory neuropathy are described. Two were detected via a
      targeted neonatal hearing screening programme based on auditory brain stem
      response testing, and one via the routine Health Visitor Distraction Test.
      Auditory neuropathy is an important but poorly understood disorder which has
      implications on planning future hearing screening policy and management of
      hearing impairment.

PMID- 12495955
TI  - The epidemiology of sudden infant death syndrome.
AB  - BACKGROUND: Twins compared to singletons are at increased risk of sudden infant
      death syndrome (SIDS). AIMS: To compare the epidemiology of SIDS in twins and
      singletons and to test the hypothesis that monozygous (MZ) were at greater risk
      of SIDS than dizygous (DZ) twins. METHODS: Data from the Office for National
      Statistics on all registered live births and infant deaths with registered cause
      of death "sudden unexpected death in infancy" in England and Wales from 1993 to
      1998 were obtained, together with the registered birth weight and, for twins,
      whether they were of like or unlike sex. RESULTS: The crude relative risk of SIDS
      in twins is twice that in singletons. There has been a significant temporal
      decline in SIDS mortality. There is also a significant increase in risk with
      decreasing birth weight for both twins and singletons. The birth weight specific
      risk of SIDS in all except for those > or =3000 g is greater in singletons than
      in twins. There is no significant difference in risk of SIDS in like compared
      with unlike sex twins. CONCLUSIONS: In spite of a lower risk of SIDS in twins
      compared with singletons for each birth weight group <3000 g, one component of
      the higher crude relative risk of SIDS in twins is attributable to the higher
      proportion of twins that are of low birth weight. A second component is the
      higher risk in twins compared with singletons for those of birth weight > or
      =3000 g. Like sex are at no greater risk than unlike sex twins, which suggests
      that zygosity is not a significant factor in SIDS.

PMID- 12495956
TI  - Altered arousal response in infants exposed to cigarette smoke.
AB  - AIMS: A failure of the arousal mechanism is a key feature in the apnoea theory
      for sudden infant death syndrome (SIDS). In infants studied at an age when the
      incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants
      have altered arousal response to standardised auditory stimuli, and/or sleep
      pattern, as recorded on overnight complex sleep polysomnography. METHODS: A
      standardised sequence of audiology stimuli was applied binaurally to 20 in utero
      smoke and non-smoke exposed infants aged 8-12 weeks during a rapid eye movement
      (REM) and NREM epoch, in a controlled (temperature, position, pacifier use,
      noise) sleep environment. Infants were monitored for 10-12 hours using complex
      sleep polysomnography. RESULTS: Five infants exposed to in utero tobacco smoke
      did not have behavioural arousal response, whereas all non-smoke exposed infants
      aroused during NREM (p = 0.016). There was, however, no difference in REM sleep,
      and the groups did not differ in routine overnight complex sleep polysomnography
      parameters. CONCLUSION: At the age when the incidence of SIDS is at its peak,
      infants of smoking mothers are less rousable than those of non-smoking mothers in
      NREM sleep; this may partly explain why such infants are more at risk of SIDS.

PMID- 12495957
TI  - Postnatal depression and infant growth and development in low income countries: a
      cohort study from Goa, India.
AB  - BACKGROUND: Postnatal depression is a recognised cause of delayed cognitive
      development in infants in developed countries. Being underweight is common in
      South Asia. AIMS: To determine whether postnatal depression contributes to poor
      growth and development outcomes in Goa, India. METHODS: Cohort study for growth
      outcomes with nested case-control study for developmental outcomes. A total of
      171 babies were weighed and measured at 6-8 weeks following birth. The following
      measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and
      sociodemographic and infant health variables. Outcome measures were: weight (<5th
      centile), length (<5th centile), and Developmental Assessment Scale for Indian
      Infants scores at six months. RESULTS: Postnatal depression was a strong, and
      independent, predictor of low weight and length and was significantly associated
      with adverse mental development quotient scores. CONCLUSIONS: This study provides
      evidence for the first time that postnatal depression, a potentially treatable
      disorder, is a cause of poor growth and development in South Asia.

PMID- 12495958
TI  - Divided by a common language.

PMID- 12495960
TI  - The doctor, the father, and the social scientist.
AB  - Life was sorted. With membership of the college under my belt, and my paediatric
      training completed, I needed a new challenge. I decided to launch into the deep
      waters of qualitative research. Stepping out with some trepidation into
      semistructured interviews and grounded theory, I soon found that the water was
      neither as deep nor as unknown as I had feared.

PMID- 12495959
TI  - Describing the phenotype in Rett syndrome using a population database.
AB  - BACKGROUND: Mutations in the MECP2 gene have been recently identified as the
      cause of Rett syndrome, prompting research into genotype-phenotype relations.
      However, despite these genetic advances there has been little descriptive
      epidemiology of the full range of phenotypes. AIMS: To describe the variation in
      phenotype in Rett syndrome using four different scales, by means of a population
      database. METHODS: Using multiple sources of ascertainment including the
      Australian Paediatric Surveillance Unit, the development of an Australian cohort
      of Rett syndrome cases born since 1976 has provided the first genetically
      characterised population based study of Rett syndrome. Follow up questionnaires
      were administered in 2000 to families and used to provide responses for items in
      four different severity scales. RESULTS: A total of 199 verified cases of Rett
      syndrome were reported between January 1993 and July 2000; 152 families provided
      information for the follow up study. The mean score using the Kerr scale was 22.9
      (SD 4.8) and ranged from 20.5 in those under 7 years to 24.2 in those over 17
      years. The mean Percy score was 24.9 (SD 6.6) and also increased with age group
      from 23.0 to 26.9. The mean Pineda score was 16.3 (SD 4.5) and did not differ by
      age group. The mean WeeFIM was 29.0 (SD 11.9), indicating extreme dependence, and
      ranged from 18 to 75. CONCLUSION: We have expanded on the descriptive
      epidemiology of Rett syndrome and shown different patterns according to the
      severity scale selected. Although all affected children are severely functionally
      dependent, it is still possible to identify some variation in ability, even in
      children with identified MECP2 mutations.

PMID- 12495961
TI  - Music for preterm babies.

PMID- 12495963
TI  - Diabetes services in the UK: third national survey confirms continuing
      deficiencies.
AB  - AIMS: To determine the current level of diabetes services and to compare the
      results with previous national surveys. METHODS: A questionnaire was mailed to
      all paediatricians in the UK identified as providing care for children with
      diabetes aged under 16 years. Information was sought on staffing, personnel,
      clinic size, facilities, and patterns of care. Responses were compared with
      results of two previous national surveys. RESULTS: Replies were received from 244
      consultant paediatricians caring for an estimated 17 192 children. A further 2234
      children were identified as being cared for by other consultants who did not
      contribute to the survey. Of 244 consultants, 78% expressed a special interest in
      diabetes and 91% saw children in a designated diabetic clinic. In 93% of the
      clinics there was a specialist nurse (44% were not trained to care for children;
      47% had nurse:patient ratio >1:100), 65% a paediatric dietitian, and in 25% some
      form of specialist psychology or counselling available. Glycated haemoglobin was
      measured routinely at clinics in 88%, retinopathy screening was performed in 87%,
      and microalbuminuria measured in 66%. Only 34% consultants used a computer
      database. There were significant differences between the services provided by
      paediatricians expressing a special interest in diabetes compared with "non
      specialists", the latter describing less frequent clinic attendance of dietitians
      or psychologists, less usage of glycated haemoglobin measurements, and less
      screening for vascular complications. Non-specialist clinics met significantly
      fewer of the recommendations of good practice described by Diabetes UK.
      CONCLUSIONS: The survey shows improvements in services provided for children with
      diabetes, but serious deficiencies remain. There is a shortage of diabetes
      specialist nurses trained to care for children and paediatric dietitians, and a
      major shortfall in the provision of psychology/counselling services. The services
      described confirm the need for more consultant paediatricians to receive
      specialist training and to develop expertise and experience in childhood
      diabetes.

PMID- 12495962
TI  - Monitoring cardiac function in intensive care.
AB  - Systolic cardiac function results from the interaction of four interdependent
      factors: heart rate, preload, contractility, and afterload. Heart rate can be
      quantified easily at the bedside, while preload estimation has traditionally
      relied on invasive pressure measurements, both central venous and pulmonary
      artery wedge. These have significant clinical limitations; however, adult
      literature has highlighted the superiority of several novel preload measures.
      Measurement of contractility and afterload is difficult; thus in clinical
      practice the bedside assessment of cardiac function is represented by cardiac
      output. A variety of techniques are now available for cardiac output measurement
      in the paediatric patient. This review summarises cardiac function and cardiac
      output measurement in terms of methodology, interpretation, and their
      contribution to the concepts of oxygen delivery and consumption in the critically
      ill child.

PMID- 12495964
TI  - Relation between measurements of cough severity.
AB  - BACKGROUND: In asthma, measurements of airway inflammation correlate poorly with
      clinical markers and airway hyperresponsiveness. While the relation between
      determinants of asthma severity is known, that for cough is unknown. We
      hypothesised that cough sensitivity changes relate to changes in cough scores and
      objectively measured cough frequency. AIMS: To examine the relation between
      commonly used outcome measurements of cough severity in children. METHODS: The
      concentration of capsaicin causing two and five or more coughs (C2 and C5
      respectively), cough frequency objectively measured using an ambulatory cough
      meter, and parent and child recorded subjective cough scores were determined in
      40 children with recurrent cough on two occasions. RESULTS: On occasion one, log
      cough frequency significantly correlated with parent and child recorded log cough
      score (r(s) = 0.32, p = 0.05; and r(s) = 0.32, p = 0.046 respectively) and
      significantly negatively correlated with log C2 (r(s)= -0.5, p = 0.005).
      Subjective cough scores did not relate to either C2 or C5. On occasion two, the
      relation between cough frequency and C2 and C5 measures was lost, but C2 had a
      weak but significant relation to parent recorded cough score (r(s) = -0.38, p =
      0.047). When the changes in the log values were determined, C5 but not C2
      significantly related to cough frequency. CONCLUSION: In children, measures of
      cough sensitivity have a weak relation with cough frequency. Subjective cough
      scores have a stronger and consistent relation with cough frequency. These cough
      severity indices measure different aspects of cough. The choice of indices
      depends on the reason for performing the measurement.

PMID- 12495965
TI  - A cohort study of neurodevelopmental outcome in children with DiGeorge syndrome
      following cardiac surgery.
AB  - AIMS: To examine whether the learning difficulties seen in a proportion of
      children with DGS are secondary to cardiac pathology and treatment, or a feature
      of the DGS phenotype. METHODS: Cohort study of all patients with DGS and
      coexisting cardiac lesions within a region. Ten children with 22q11 deletion were
      assigned two controls each, matched for age, sex, cardiac lesion, and
      preoperative hemodynamic status but without DGS. The neurodevelopmental status
      was evaluated with the Ruth Griffiths test for babies and young children.
      RESULTS: Children with the 22q11 deletion showed a wide range of developmental
      quotient (DQ; mean 71, 95% CI 47 to 95) and subscale scores, but these as a group
      were significantly lower than those of the control group (DQ 113, 95% CI 108 to
      118). Four of the DGS children had DQs below 60. Hypocalcaemia, prolonged
      postoperative ventilation, and abnormal neurology perioperatively were associated
      with a low DQ. CONCLUSIONS: A proportion of children with DGS have a very poor
      developmental outcome following cardiac surgery. This outcome is not attributable
      to the cardiac condition and its treatment alone, but represents either a pre
      existing component of the syndrome or an interaction between the syndrome and its
      treatment.

PMID- 12495966
TI  - The use of regional anaesthetic blockade in a child with recurrent
      erythromelalgia.
AB  - Primary erythromelalgia is a rare condition, which is characterised by redness,
      burning pain, and increased temperature of the extremities. We describe a 6 year
      old boy with symptoms of erythromelalgia and the difficulty surrounding treatment
      of this condition. Severe pain responded to the use of regional anaesthetic
      blocks.

PMID- 12495967
TI  - Successful treatment with interferon alfa in infiltrating angiolipoma: a case
      presenting with Kasabach-Merritt syndrome.
AB  - We report a case of infiltrating angiolipoma who presented with a large mass on
      the shoulder and the signs of Kasabach-Merritt syndrome. She improved
      dramatically within one month and the mass completely disappeared after six
      months of interferon treatment.

PMID- 12495968
TI  - Prolonged hypothermia following respiratory syncytial viral infection in infancy.
AB  - Following proven respiratory syncytial viral infection, a previously healthy 2
      year old boy displayed notable persistent hypothermia-the lowest temperature
      being 34.2 degrees C. No obvious ill effects were observed.

PMID- 12495970
TI  - Is there a role for treatment of asthma with omalizumab?
AB  - The allergic response is distinct from other immune reactions in its reliance on
      IgE, its high affinity receptor, Fc epsilon RI, and the primary effector cell-
      the tissue mast cell. Positive skin tests or raised concentrations of specific
      immunoglobulin E (IgE) in the serum define IgE sensitisation or "atopy". IgE
      participates both in immediate hypersensitivity response and in the induction of
      chronic allergic inflammation. It enhances allergen capture and 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.

PMID- 12495971
TI  - Respiratory problems in children with neurological impairment.
AB  - Children with severe neurological impairment have a high incidence of respiratory
      problems which are multifactorial and may be related to or dependent on the
      underlying disability. In addition, common respiratory conditions such as asthma
      will be represented in this group as in the general paediatric population. In
      order to maximise quality of life and reduce morbidity and mortality, each child
      should be carefully assessed and treated, making adjustments where necessary in
      the treatment regime to take account of the disability.

PMID- 12495972
TI  - Food allergy in childhood.

PMID- 12495973
TI  - Towards evidence based medicine for paediatricians.

PMID- 12495974
TI  - Should we glue lip lacerations in children?

PMID- 12495975
TI  - Is nebulised tolazoline an effective treatment for persistent pulmonary
      hypertension of the newborn?

PMID- 12495976
TI  - How good is clinical examination at detecting a significant patent ductus
      arteriosus in the preterm neonate?

PMID- 12495977
TI  - Hypothermia in a child secondary to ibuprofen.

PMID- 12495978
TI  - Intravenous atropine treatment in infantile hypertrophic pyloric stenosis.

PMID- 12495979
TI  - Vagal overactivity: a risk factor of sudden infant death syndrome?

PMID- 12495980
TI  - Perforated duodenal ulcer disclosing medium chain acyl-CoA dehydrogenase
      deficiency.

PMID- 12495981
TI  - Short versus standard duration antibiotic treatment for UTIs: a comparison of two
      meta-analyses.

PMID- 12495982
TI  - Glucose metabolism in sleep disordered breathing.

PMID- 12495983
TI  - Management of childhood osteoporosis.

PMID- 12495984
TI  - Newborn screening for Duchenne muscular dystrophy.

PMID- 12495985
TI  - Is life long follow up for patients with Kawasaki disease indicated?

PMID- 12495986
TI  - Differential diagnosis of periodic fevers.

PMID- 12495987
TI  - Mechanisms of pulmonary hypertension in Bordetella pertussis.

PMID- 12495988
TI  - The effect of sanctions on children of Iraq.

PMID- 12495990
TI  - Proceedings of the International Symposium on Visualization and Imaging in
      Transport Phenomena organized by the International Center for Heat and Mass
      Transfer and the Visualization Society of Japan. May 5-10, 2002. Antalya, Turkey.

PMID- 12495991
TI  - Quantitative flow visualization: toward a comprehensive flow diagnostic tool.
AB  - Quantitative flow visualization has many roots and has taken several approaches.
      The advent of digital image processing has made it practical to extract useful
      information from every kind of flow image. In a direct approach, the image
      intensity or color (wavelength or frequency) can be used as an indication of
      concentration, density and temperature field, or gradients of these scalar fields
      in the flow.(1) For whole-field velocity measurement, the method of choice for
      experimental fluid mechanicians has been digital particle image velocimetry
      (DPIV). This paper presents a novel approach to extend the DPIV technique from a
      planar method to a full three-dimensional volume mapping technique.

PMID- 12495992
TI  - Image flows and one-liner graphical image representation.
AB  - This paper introduces a novel graphical image representation consisting of a
      single curve-the one-liner. The first step of the algorithm involves the
      detection and ranking of image edges. A new edge exploration technique is used to
      perform both tasks simultaneously. This process is based on image flows. It uses
      a gradient vector field and a new operator to explore image edges. Estimation of
      the derivatives of the image is performed by using local Taylor expansions in
      conjunction with a weighted least-squares method. This process finds all the
      possible image edges without any pruning, and collects information that allows
      the edges found to be prioritized. This enables the most important edges to be
      selected to form a skeleton of the representation sought. The next step connects
      the selected edges into one continuous curve-the one-liner. It orders the
      selected edges and determines the curves connecting them. These two problems are
      solved separately. Since the abstract graph setting of the first problem is NP
      complete, we reduce it to a variant of the traveling salesman problem and compute
      an approximate solution to it. We solve the second problem by using Dijkstra's
      shortest-path algorithm. The full software implementation for the entire one
      liner determination process is available.

PMID- 12495993
TI  - Simulation and identification of deterministic structures in thermal and magnetic
      convection.
AB  - Large-scale vortical structures, found in many flows in nature, in laboratory or
      industrial equipment, have often a deterministic character. Simulation,
      identification, visualization, and interpretation of such structures is essential
      for understanding the physics of turbulence and transport processes, and for
      their control, but still poses a challenge especially in complex flows at high
      Reynolds and Rayleigh numbers. We show that such structures can be simulated by a
      transient Reynolds-averaged Navier-Stokes (T-RANS) approach. Various structure
      identification methods show that the captured deterministic structures resemble
      closely those obtained from experiments or direct numerical simulations (DNS).
      The potential of the T-RANS method is illustrated by examples of classical and
      magnetic Rayleigh-Benard (R-B) convection in a range of Rayleigh numbers that are
      at present inaccessible to experiments or other simulation techniques.

PMID- 12495994
TI  - A new definition of contours in images applications in heat and mass transfer.
AB  - A new definition for the contours of objects used in experimental visualization
      is proposed and used for edge detection and image smoothing in infrared
      thermography. This work is a contribution to image analysis, in the search for
      outlines of the features and their structures, aimed at identifying the trends
      they represent. A good example is the discovery of structures in the flow of
      liquids.

PMID- 12495995
TI  - Photogrammetric and image processing aspects in quantitative flow visualization.
AB  - The development of a measurement system for the visualization, topological
      classification, and quantitative analysis of complex flows in large-scale wind
      tunnel experiments is described. A new approach was sought in which the
      topological features of the flow (e.g., stream lines, separation and reattachment
      regions, stagnation points, and vortex lines) were extracted directly and
      preferably visualized in real-time in a virtual wind tunnel environment. The
      system was based on a stereo arrangement of two CCD cameras. A frame rate of 120
      fps allowed measurements at high flow velocities. The paper focuses on the
      problem of fast and accurate reconstruction of path lines of helium filled soap
      bubbles in three dimensions (3D). A series of simple algorithmic steps was
      employed to ensure fast data processing. These included fast image segmentation,
      a spline approximation of the path lines, a camera model, point correspondence
      building, calculation of path line points in 3D and creation of a three
      dimensional spline representation. The path lines, which contained both velocity
      and topological information, were analyzed to extract the relevant information.

PMID- 12495996
TI  - Color interpolation algorithms in visualizing results of numerical simulations.
AB  - The paper addresses the application of graphical replenishment (GR) color
      interpolation algorithms for visualizing numerical simulation of physical
      processes in order to enhance the information density of the graphic
      interpretation of these processes. The GR algorithms presented here may be
      successfully applied to two- and three-dimensional grids, and grids of various
      structures.

PMID- 12495997
TI  - Visualization of molecular dynamics by simulation.
AB  - The mechanism of formation of methane hydrate is investigated here at a molecular
      level. The key to whether or not methane hydrates can be formed is the stability
      of the hydrate structure. This paper deals with a computer simulation of methane
      hydrate type 1 formation by a molecular dynamics method and an accurate
      description of the crystal structure. Computer simulation results show that very
      stable type 1 methane hydrates can be formed below 275 K, in which 46 water and 8
      methane molecules are contained in a single cubic unit cell of length 12.0 A.
      Above 275 K, the stability of the hydrates increasingly degrades, logarithmically
      as a power function, up to 300 K, with no stability at 350 K. Pressure, as a
      parameter of formation conditions, increases with temperature and becomes
      tremendously high at 350 K. Hydrates with various hydration numbers (at least one
      guest molecule in a small cage) have roughly the same degree of stability, but
      higher pressures are required for hydrates with fewer guest molecules. Empty
      hydrates dissolve above 275 K.

PMID- 12495998
TI  - Vortex scale of unsteady separation on a pitching airfoil.
AB  - The streaklines of unsteady separation on two kinds of pitching airfoils, the
      NACA65-0910 and a blunt trailing edge airfoil, were studied by dye flow
      visualization and by the Schlieren method. The latter visualized the discrete
      vortices shed from the leading edge. The results of these visualization studies
      allow a comparison between the dynamic behavior of the streakline of unsteady
      separation and that of the discrete vortices shed from the leading edge. The
      influence of the airfoil configuration on the flow characteristics was also
      examined. Furthermore, the scale of a discrete vortex forming the recirculation
      region was investigated. The non-dimensional pitching rate was k = 0.377, the
      angle of attack alpha(m) = 16 degrees and the pitching amplitude was fixed to A =
      +/-6 degrees for Re = 4.0 x 10(3) in this experiment.

PMID- 12495999
TI  - Imaging the transient boundary layer on a free rotating disc.
AB  - This report presents a visual study of the transition process of the laminar
      boundary layer (BL) in a turbulent BL on a free rotating disc. The imaging is
      based on an experimental investigation that aimed to analyze the structure of the
      BL by relating it to the ratio between turbulent energy and vortex energy, the
      critical and the transient Reynolds numbers (Re), the vortex numbers and their
      dependence on Re, and on the distance from the rotating disc.

PMID- 12496000
TI  - Effects of a splitter plate in the near wake of a divergent trailing edge.
AB  - This paper discusses experimental research aimed at defining a base drag
      reduction device based on splitter plates. The unsteady three-dimensional nature
      of the flow is studied by Schlieren photography, particle image velocimetry, and
      measurement of the total unsteady lift and drag loads.

PMID- 12496001
TI  - Start-up behavior of viscoelastic fluid flow near a capillary entry.
AB  - The effect of elasticity on the capillary entry flow development process was
      investigated by applying a laser doppler velocimeter (LDV) and flow
      visualization. The fluid filling the test section was kept at rest under a
      pressure of compressed air or a natural head and then a valve below the capillary
      was quickly opened to start the flow. Although the development of the capillary
      entry flow field of a Newtonian fluid is virtually quasi-steady, it takes a
      considerable time for a viscoelastic PAA-solution to attain its terminal regime.
      The transient behavior of the flow rate of the PAA-solution is attributed to the
      gradual development process of the flow field upstream from the entry.

PMID- 12496002
TI  - Development and validation of an X-ray tomograph for two-phase flow.
AB  - This paper describes the development and validation of a high spatial resolution
      X-ray tomograph designed for the investigation of air-water two-phase flow. The
      device hardware mainly comprises a 60 keV X-ray source, a detector, and an
      accurate mechanical bench. Our study concentrated on accurate quantification with
      emphasis on the reconstruction procedure. As is well known, absorption gradients
      induce reconstruction artifacts when using standard algorithms based on uniform
      regularization. In the particular case of two-phase flow in a pipe, this leads to
      poor measurement accuracy in the vicinity of the walls. To overcome such effects,
      improved algorithms were developed during this study that involve spatially
      adaptive regularization methods. Preliminary calibration performed on static
      phantoms clearly exhibited the benefits of the advanced reconstruction
      algorithms. A validation procedure was carried out on an air-water bubble column,
      equipped with an optical probe, which could be translated in order to explore the
      80 mm x 80 mm square cross section. Comparisons of local void fraction
      measurements were performed pixel by pixel. They demonstrate the accuracy
      improvement induced by the advanced reconstruction algorithms.

PMID- 12496003
TI  - Visualization of turbulent wedges under favorable pressure gradients using shear
      sensitive and temperature-sensitive liquid crystals.
AB  - Turbulent wedges induced by a three-dimensional surface roughness placed on a
      flat plate were studied using both shear sensitive and temperature sensitive
      liquid crystals, respectively denoted by SSLC and TSLC. The experiments were
      carried out at a free-stream velocity of 28 m/sec at three different favorable
      pressure gradients. The purpose of this investigation was to examine the
      spreading angles of the turbulent wedges, as indicated by their associated
      surface shear stresses and heat transfer characteristics, and to obtain more
      insight about the behavior of transitional momentum and thermal boundary layers
      when a streamwise pressure gradient exists. It was shown that under a zero
      pressure gradient the spreading angles indicated by the two types of liquid
      crystals are the same, but the difference increases as the level of the favorable
      pressure gradient increases. The result from the present study is important for
      modelling the transition of thermal boundary layers over gas turbine blades.

PMID- 12496004
TI  - Visualization and measurement of multiphase flow in porous media using light
      transmission and synchrotron x-rays.
AB  - Non-aqueous phase liquids enter the vadose zone as a result of spills or leaking
      underground storage facilities, thus contaminating groundwater resources.
      Measuring the contaminant concentrations is important in assessing the risk to
      human health and the environment and to develop effective remediation. This
      research presents the development and application of the light transmission
      method (LTM) for three-phase flow systems, aimed at investigating unstable
      fingered flow in a soil-air-oil-water system. The LTM uses the hue and intensity
      of light transmitted through a slab chamber to measure fluid content, since total
      liquid content is a function of both hue and light intensity. Evaluation of the
      LTM is obtained by comparing experiments with LTM and synchrotron X-rays. The LTM
      captures the spatial resolution of the fluid contents and can provide new
      insights into rapidly changing, two-phase and three-phase flow systems.
      Application of the LTM as a visualization technique for environmental and
      physical phenomena is noted. Visualization by LTM of groundwater remediation by
      surfactants as well as visualization of model cluster growth and fractal
      dimensions was also explored.

PMID- 12496005
TI  - Assessment of physiologic and pathologic radiative heat dissipation using dynamic
      infrared imaging.
AB  - This paper reviews the mechanism and assessment of regulated radiative heat
      dissipation, involving the circulatory system and the skin. It describes the
      quantitative assessment of skin temperature modulation. The main regulating
      process, which can be quantitatively monitored by fast and sensitive dynamic
      infrared imaging, involves autonomic nervous control of cutaneous and
      subcutaneous perfusion. This control is significantly affected by a variety of
      local or systemic pathologic conditions, including cancer and certain
      neuropathies. A potential clinical application that objectively assesses local
      attenuation of temperature modulation in the presence of breast cancer is
      described in some detail. Systemic aberrations in skin temperature modulation can
      be clinically useful also in neurology. It can be used also in psychology and
      psychiatry to evaluate transient effects of mental stress on the autonomic
      nervous system.

PMID- 12496006
TI  - Molecular motion and cardiac muscle motor dynamics.
AB  - This paper reports on the kinetics of molecular motion in cardiac (and skeletal)
      muscles, studied by image analysis of the motility assay of an isolated actin
      filament sliding over isolated myosin heads that perform as linear motors. Image
      analysis allows us to study the dynamics of the crossbridges (Xbs) formed by the
      interactions between the actin molecule and the myosin heads, and to explore the
      rate kinetics of the interactions between the two. A most significant result
      pertains to the identification and characterization of two kinds of kinetics
      involved in Xb dynamics. The analysis of the acquired images suggests that Xb
      dynamics is determined by two distinctive kinetic mechanisms: fast physical
      kinetics that relates to the actin-myosin Xb attachment and detachment cycle and
      a process that is orders of magnitude slower in biochemical kinetics that relates
      to the reactions of nucleotide binding and dissociation.

PMID- 12496007
TI  - Modeling the spreading cortical depression wavefront.
AB  - Spreading cortical depression (SCD) is a wave of depolarization that spreads
      across the cortex at 2-5 mm/min and is followed by a 5-10 minute reduction in EEG
      activity. It is assumed that SCD is involved in the pathophysiology of migraine.
      We present a new model and a visualization technique for the spread of excitation
      on realistic brain surfaces. The usefulness of the technique is demonstrated on a
      rat brain that had been segmented from a three-dimensional magnetic resonance
      image data set. With the help of this methodology it is possible to create
      specific patient models to better understand the mechanisms of SCD.

PMID- 12496008
TI  - Time-varying current density distributions in the human heart and brain.
AB  - A new method for visualizing and postprocessing three-dimensional time varying
      vector fields is presented. This method is based on equivalent ellipsoids fitted
      to these fields. The new technique has been tested on vector fields representing
      current density reconstruction results based on biomagnetic data from a cardiac
      patient and a neurological patient. Multiple foci in the vector fields are
      extracted by multiple ellipsoids which are fitted in an iterative manner. The new
      method enables visualization of even very complex vector fields, as well as
      statistical postprocessing.

PMID- 12496009
TI  - Neutrophils movement in vitro.
AB  - Ineffectiveness of the motility of neutrophils is observed in some
      immunodeficiency disorders. There is a need to find an adequate description and
      means to evaluate the activity of neutrophils. Early studies describe an
      individual cell behavior by the cell motility index vector with three components:
      penetration, directionality, and expansivenesses. Movement quantification has
      been improved by extending the description of cell activity to two stages of
      classification. In the first stage, one minute of each cell's behavior is
      classified into one of five types of cell behavior, using the k-NN method. In the
      second stage, the sample level that corresponds to the final classification, the
      Shapiro-Francio test has been used. The proposed new method allows us to describe
      differences between a normal child and a Chediak-Higashi syndrome patient.

PMID- 12496010
TI  - An algorithm for estimating chaos in mechanoemission of blood and magnetic
      resonance imaging in patients with gastric cancer.
AB  - The paper describes an algorithm and computational system used to estimate the
      spatial chaos of magnetic resonance images of patients with gastric cancer and
      the quantum chaos of mechanoemission in blood.

PMID- 12496011
TI  - Microscopic study of crystal growth in cryopreservation agent solutions and
      water.
AB  - Ice formation inside or outside cells during cryopreservation is evidently the
      main factor of cryoinjury to cells. In the study described here a high voltage DC
      electric field and a cryomicroscopic stage were used to test DMSO and NaCl
      solutions under electric field strengths ranging from 83 kV/m to 320 kV/m.
      Dendritic ice crystals became asymmetric when the electric field was activated.
      This change in the ice crystal shape was more pronounced in the ionic NaCl
      solution. In addition, ice growth of distilled water without an electric field
      was tested under different cooling rates.

PMID- 12496012
TI  - Temperature and flow visualization in a simulation of the Czochralski process
      using temperature-sensitive liquid crystals.
AB  - There is no doubt today that thermal and thermocapillary convection play a
      dominant role in momentum, heat, and mass transfer in the Czochralski crystal
      growth method. Because of the complexity of the problems, measurements in one
      point of the volume are not sufficient to illuminate the flow topography or to
      compare the experimental results with real or numerically simulated data.
      Therefore, it is of great interest to measure the temperatures and velocities in
      the whole field in order to qualitatively analyze thermally driven convection.
      The new experimental particle image thermometry method, based on computer-aided
      color analysis of the TLCs reported here, enables the simultaneous determination
      of the temperature and velocity fields.

PMID- 12496013
TI  - Visualization of droplet boiling on heated transparent solid surfaces with
      various thermal properties.
AB  - The purpose of the research described in this paper is to elucidate the
      phenomenon of miniaturization boiling, which involves the scatter of a large
      number of minute liquid particles from a droplet surface to the atmosphere when
      the droplet impinges on a solid heating surface. This behavior was photographed
      from the underside of the heating surface, with special attention to the liquid
      solid contact. Transparent solid surfaces with various thermal properties
      included sapphire, glass with indium tin oxide coating, quartz, and quartz with
      chromium coating.

PMID- 12496014
TI  - Ice/water slurry blocking phenomenon at a tube orifice.
AB  - The phenomenon of ice-particle/water mixture blocking flow through a pipeline is
      a problem that needs to be solved before mixture flow can be applied for
      practical use in cold energy transportation in a district cooling system. In this
      work, the blocking mechanism of ice-particle slurry at a tube orifice is
      investigated and a criterion for blocking is presented. The cohesive nature of
      ice particles is shown to cause compressed plug type blocking and the compressive
      yield stress of a particle cluster is presented as a measure for the cohesion
      strength of ice particles.

PMID- 12496015
TI  - Convective heat transfer and infrared thermography.
AB  - Infrared (IR) thermography, because of its two-dimensional and non-intrusive
      nature, can be exploited in industrial applications as well as in research. This
      paper deals with measurement of convective heat transfer coefficients (h) in
      three complex fluid flow configurations that concern the main aspects of both
      internal and external cooling of turbine engine components: (1) flow in ribbed,
      or smooth, channels connected by a 180 degrees sharp turn, (2) a jet in cross
      flow, and (3) a jet impinging on a wall. The aim of this study was to acquire
      detailed measurements of h distribution in complex flow configurations related to
      both internal and external cooling of turbine components. The heated thin foil
      technique, which involves the detection of surface temperature by means of an IR
      scanning radiometer, was exploited to measure h. Particle image velocimetry was
      also used in one of the configurations to precisely determine the velocity field.

PMID- 12496016
TI  - Visualization of flow and heat transfer augmentation by oblique impingement jets.
AB  - Various nozzle geometries for impingement cooling jets have recently been devised
      and favorable designs for cooling effectiveness have been reported. However,
      impinging flow and the characteristics of impingement cooling are not
      sufficiently clear. This paper reports on an investigation of impingement jet
      cooling techniques. The impingement cooling characteristics by oblique jets
      through a rectangular nozzle have been clarified. Preliminary numerical
      simulations have not necessarily presented the details of heat transfer
      characteristics of the oblique jets.

PMID- 12496017
TI  - Unsteady flow patterns in the vicinity of heated wall-mounted transverse ribs.
AB  - This paper deals with experimental modeling of the unsteady junction flow
      features in the vicinity of an isoflux heated wall with mounted insulated
      rectangular ribs representing three distinctive ribbed test geometries. Both flow
      visualizations and surface temperature distributions show that the blockage
      effect upstream of the ribs, as well as the presence of complex eddy structures
      inside the open cavities, significantly affect the heat transfer process. All the
      configurations indicate degraded heat transfer performance in the area close to
      the ribs and an enhancement just downstream from the last rib.

PMID- 12496018
TI  - Investigation of transport phenomena inside a microcapsule.
AB  - Mass transfer within a microcapsule is enhanced by convection, achieved by
      introducing a movable body inside the microcapsule. This body has a different
      density from the fluid within the microcapsule and can be moved relative to the
      microcapsule by application of an external force, such as a magnetic field or
      acceleration/deceleration. The effect of the transport improvement was
      investigated as a function of the Peclet number (Pe) by using computational fluid
      dynamics and particle image velocimetry. The results show that the period to
      achieve 80% saturation in the microcapsule was reduced by 60% with a movable body
      with half of the diameter of the microcapsule and Pe = 600, compared to the mass
      transport in the microcapsule with a non-movable body.

PMID- 12496019
TI  - Measurement of the density of CO(2) solution by Mach-Zehnder interferometry.
AB  - The density of CO(2) solution was measured by using Mach-Zehnder interferometry
      in the pressure range from 5.0 to 12.5 MPa, at temperatures from 273.25 to 284.15
      K, and CO(2) mass fraction in solution up to 0.061. It was found that the density
      difference between the CO(2) solution and pure water at the same pressure and
      temperature is monotonically linear with the CO(2) mass fraction. The slope of
      this linear function, calculated by experimental data fitting, is 0.275.

PMID- 12496020
TI  - Particle image velocimetry and thermometry for two-phase flow problems.
AB  - Image processing in fluid mechanics has become an important quantitative tool for
      flow analysis. The feasibility of simultaneous measurements of instantaneous
      velocity and temperature fields, as well as for tracking interfaces, creates a
      functional tool to describe thermally driven flows accompanied by phase change.
      The information thus gathered is essential for the verification and validation of
      computation models. The paper reviews the image processing methods developed by
      the author and his coworkers to analyze typical problems of two-phase flow.
      Simultaneous measurement of temperature and velocity fields, obtained by using
      liquid crystal tracers, are applied to elucidate solidification and growing vapor
      bubble problems.

PMID- 12496021
TI  - Multiphase bubbly flow visualization using particle image velocimetry.
AB  - This article describes advances made in using particle image velocimetry (PIV)
      techniques in the study of multiphase bubbly flow. One of the fundamental issues
      in bubbly flow is the prediction of the velocity field. A methodology that allows
      for velocity field measurements of both components of a two-phase bubbly flow is
      presented. The bubble shape is also constructed via a shadow imaging technique
      combined with PIV.

PMID- 12496022
TI  - Velocity measurements by particle image velocimetry using a direct
      intercorrelation algorithm: application to the interaction between a water mist
      and a liquid pool fire.
AB  - The aim of this study was to obtain better characterization of the interaction
      between a water mist and a diffusion flame of small-scale size. A PIV algorithm
      was used to determine the flow pattern with and without a water mist and its
      relation to the velocity of water droplets.

PMID- 12496023
TI  - Visualization of bubble-fluid interaction by a moving object flow image analyzer
      system.
AB  - This paper deals with interaction between a bubble and fluid around it,
      visualized by a moving object flow image analyzer (MOFIA) consisting of a three
      dimensional (3D) moving object image analyzer (MOIA) and two-dimensional particle
      image velocimetry (PIV). The experiments were carried out for rising bubbles of
      various sizes and shapes in stagnant water in a vertical pipe. In the MOFIA
      employed, 3D-MOIA was used to measure bubble motion and PIV to measure fluid
      flow. The 3D position and shape of a bubble and the velocity field were measured
      simultaneously. The experimental results showed that the interaction was
      characterized by the shape, size and density of a bubble. Concretely, they showed
      the characteristics of bubble motion, wake shedding, and flow field.

PMID- 12496024
TI  - Effect of electrolytes on bubble coalescence in columns observed with
      visualization techniques.
AB  - Bubble coalescence and the effect of electrolytes on this phenomenon have been
      previously studied. This interfacial phenomenon has attracted attention for
      reactor design/operation and enhanced oil recovery. Predicting bubble coalescence
      may help prevent low yields in reactors and predict crude oil recovery. Because
      of the importance of bubble coalescence, the objectives of this work were to
      improve the accuracy of measuring the percentage of coalescing bubbles and to
      observe the interfacial gas-liquid behavior. An experimental setup was designed
      and constructed. Bubble interactions were monitored with a visualization setup.
      The percentage of air bubble coalescence was 100% in distilled water, about 50%
      in 0.1 M sodium chloride (NaCl) aqueous solution, and 0% in 0.145 M NaCl aqueous
      solution. A reduction of the contact gas-liquid area was observed in distillate
      water. The volume of the resulting bubble was the sum of the original bubble
      volumes. Repulsion of bubbles was observed in NaCl solutions exceeding 0.07 M.
      The percentage of bubble coalescence diminishes as the concentration of NaCl
      chloride increases. High-speed video recording is an accurate technique to
      measure the percentage of bubble coalescence, and represents an important advance
      in gas-liquid interfacial studies.

PMID- 12496025
TI  - X-ray-based flow visualization and measurement: application in multiphase flows.
AB  - Information concerning continuous or discreet phase flow in multiphase systems is
      desired for various practical and analytical applications. The potential of X-ray
      based flow visualization and measurement of multiphase flow is demonstrated here
      by two non-intrusive methods: (1) Measurement of the three-dimensional (3D)
      velocity field of the continuous liquid phase in a bubble column by X-ray-based
      particle tracking velocimetry (PTV) of seeded particles. (2) Liquid flow
      visualization in a bubble column by injecting an X-ray absorbing liquid into the
      bubble column. X-rays have the advantage that they are not affected by the
      various refraction indices of the multiphase system and penetrate the multiphase
      flow in undistorted straight lines. Hence, in contrast to optical methods, both
      of these X-ray-based methods are independent of the void fraction and are
      applicable to opaque liquids.

PMID- 12496026
TI  - Simultaneous velocity and concentration measurements of a turbulent jet mixing
      flow.
AB  - A method for the simultaneous measurement of velocity and passive scalar
      concentration fields by means of particle image velocimetry (PIV) and planar
      laser induced florescence (PLIF) techniques is described here. An application of
      the combined PIV-PLIF system is demonstrated by performing simultaneous velocity
      and concentration measurements in the near field of a turbulent jet mixing flow.
      The distributions of the ensemble-averaged velocity and concentration, turbulent
      velocity fluctuation, concentration standard deviation, and the correlation terms
      between the fluctuating velocities and concentration in the near field of the
      turbulent jet flow are presented as the measurement results of the simultaneous
      PIV-PLIF system.

PMID- 12496027
TI  - PIV measurement and numerical analysis of a new refrigeration compartment of a
      refrigerator.
AB  - A new cooling duct system was developed in order to increase the refrigerator
      performance in terms of uniform temperature distribution particle image
      velocimetry (PIV) and the commercial software FLUENT was used to compare the
      performance of the conventional cooling system with the new cooling system. The
      new cooling system effectively cooled the door basket region, thus increasing the
      uniformity of the temperature distribution in the refrigeration compartment.

PMID- 12496028
TI  - Visualization of jet flows over a plate by pressure-sensitive paint experiments
      and comparison with CFD.
AB  - Flow fields created by underexpanded sonic jets impinging on an inclined flat
      plate were studied experimentally using the pressure sensitive paint (PSP)
      measurement technique. The measurement system and some representative results are
      presented here. Two binders, thin-layer chromatography (TLC) plates and anodized
      aluminum (A-A) plates were tested with bathophen ruthenium chloride as a
      luminophore. The results show that both the binders can be used. TLC plates are
      preferable because their luminescent intensity is almost twice that of the A-A
      plates. Quantitative measurements require accurate temperature calibration. A
      preliminary effort to elucidate the flow structure by combining the PSP results
      with a computer simulation of the same flow field is presented. Although good
      agreement is obtained between the experimental and numerical results, future
      quantitative comparisons are necessary to yield a useful tool in the analysis of
      the jet-plate interaction flows.

PMID- 12496030
TI  - Visualization and phase doppler particle analysis measurements of oscillating
      spray propagation of an airblast atomizer under typical engine conditions.
AB  - Propagation of a kerosene spray formed by a prefilming airblast atomizer within a
      pulsating flame has been investigated. The measurements were performed in a 400
      kW single combustor rig at typical engine conditions of up to 0.8 MPa inlet
      pressure and 673 K inlet temperature. The homogeneity of the fuel spray
      propagation in the reacting zone substantially influences the local temperature
      distribution in the reaction zone and, therefore, the formation of thermal
      NO(chi). Phase locked visualization of the spray propagation and the flame
      luminescence was applied to the pulsating combustion process in order to analyze
      the complex interaction between the time dependent flow field, the spray
      propagation, and the combustion process. The spray characteristic was
      additionally investigated by means of time resolved PDPA measurements in the
      reacting flow.

PMID- 12496029
TI  - Transonic injection in interaction with transverse compressible flow.
AB  - An extensive study devoted to modelling blade cooling was undertaken at CEAT a
      few years ago in collaboration with SNECMA. For the turbomachinery applications,
      an experimental configuration of a turbulent boundary layer with heat transfer
      was studied for compressible and incompressible flows. The research presented
      here is a part of that study and this paper reports on the experimental results
      of an investigation concerned with a row of transonic jets interacting with a
      transverse flow. In many applications, the cooling layer does not emerge onto the
      surface from a tangential slot but comes from a slot normal to or inclined to
      what is otherwise a flush surface. In this case the freestream interacts with the
      coolant flow. The secondary (jet) flow is introduced at an angle of 45 degrees to
      the mainstream flow direction. Visualization studies using the surface flow
      patterns and surface temperature flow patterns are reported and discussed.

PMID- 12496031
TI  - Numerical visualization of two-phase plume formation in a stratification flow
      environment.
AB  - Evolution of two-phase plumes driven by air bubble buoyancy in a stratification
      ambient in a rectangular tank is visualized numerically by means of two-phase
      flow theory and large-eddy simulation technology. With a focus on the discrete
      nature of the buoyant dispersed phase and the role of momentum exchange between
      two phases in plume formation, we investigated the phenomena of mass entraining
      in and peeling-out for continuous phase plume, which may result from a
      complicated and intricate interplay with phase interaction and dynamic stability
      of the stratification ambient, respectively. Numerical simulations show that
      although mass entraining-in and peeling-out appear to be distinguished entirely
      in the vertical direction, they interact or couple locally within inner of the
      plume and present a discontinuity in nature. The numerically visualized three
      dimensional density field also indicates the same plume characteristics.

PMID- 12496032
TI  - Visualization studies of an acoustically excited liquid sheet.
AB  - The interaction between atomizing air and a liquid sheet initiates interfacial
      instabilities that develop into large amplitude waves, which ultimately promote
      liquid disintegration. However, to reduce atomizing airflow, the dynamic
      influence of the surrounding gas is not sufficient to affect the inner core of
      the liquid. In other words, the characteristic length scales of perturbation
      promoting break-up are small in comparison with the initial liquid momentum.
      Therefore, to enhance the disintegration process, the intact liquid-core near the
      nozzle outlet must be influenced by artificial or external excitations. To
      accomplish this, the present investigation employed a plane laminar liquid-sheet
      that was perturbed by acoustic excitations at an optimum frequency through the
      impinging air-streams.

PMID- 12496033
TI  - Flow characteristics of two immiscible liquid layers subjected to a horizontal
      temperature gradient.
AB  - Marangoni convection, driven by an interfacial instability due to a surface
      tension gradient, presents a significant problem in crystal growth in normal
      microgravity environments. It is important to suppress and control the convection
      phenomenon for better material processing, especially in crystal growth by the
      liquid encapsulated Czochralski or liquid encapsulated floating zone techniques,
      in which the melt is encapsulated in an immiscible medium. Marangoni convection
      can occur on the liquid-liquid interface and on the gas-liquid free surface.
      Buoyancy driven convection can also affect and complicate the flow. In the study
      we report here, experiments were carried out with two liquid layers, silicone oil
      and fluorinert, in an open and enclosed rectangular cavity. The flow in the
      cavity was subjected to a horizontal temperature gradient. The interactive flow
      near the liquid-liquid interface was measured by the particle image velocimetry
      technique. The measured flow field is in agreement with numerical predictions.
      Free surface fluctuations with several dominant frequencies were also measured.

PMID- 12496034
TI  - Quantification of myocardial microcirculatory function with X-ray CT.
AB  - A mathematical model of the intramyocardial coronary microcirculation is used to
      explore the validity of a fast CT imaging method for characterizing the
      myocardial microcirculatory functional status. The fast CT method depends on the
      demonstrated CT-based estimation of myocardial perfusion (F) and the
      intramyocardial blood volume (B(v)). The observed curvilinear myocardial blood
      volume-to-flow relationship, empirically fitted to B(v) = a.F + b.F(0.5), is a
      signature of the underlying early pathophysiologic processes thought to be
      involved in systemic disease processes, such as atherosclerosis, hypertension,
      and diabetes mellitus. The sensitivity and specificity of the CT-based estimate
      of this characteristic relationship is explored by altering the characteristics
      of the vascular diameter-to-flow relationship and the variation in the fraction
      of capillaries perfused at different coronary flows. The simulation results also
      indicate that if the vascular diameters change so that the vascular resistance
      corresponds to the change in flow, then the empirically observed myocardial B(v)
      to-F relationship holds well.

PMID- 12496035
TI  - Renal handling of X-ray contrast media imaging and exploration with electron beam
      CT.
AB  - Physiologic changes in renal hemodynamics and function reflect its role as a
      regulatory organ in maintaining homeostasis, whereas other alterations may mirror
      development of renal injury and often precede overt signs of morphologic changes.
      Furthermore, intrarenal alterations may be discreet and manifest only in the
      renal cortical, medullary, or papillary zones. The high spatial and temporal
      resolution of electron-beam computed tomography enables external detection and
      quantification of cortical, medullary, and papillary tissue density changes
      following an intravenous bolus injection of X-ray contrast media. These changes
      reflect flow of contrast media in these renal zones through the successive renal
      vascular, glomerular, and tubular compartments that can be individually plotted
      as time-density curves (TDC). Mathematical modeling then allows calculation of
      unique parameters of renal function from these TDC. This ability to quantify
      renal regional attributes may not only shed light on the physiologic mechanisms
      that the kidney controls, but also assist in detecting subtle impairment in its
      function.

PMID- 12496036
TI  - Visualization of blood microcirculation parameters in human tissues by time
      integrated dynamic speckles analysis.
AB  - Statistical analysis of images of time-integrated non-stationary speckle patterns
      is a tool for diagnostics and imaging of in vivo dynamics of blood
      microcirculation in superficial layers of tissues and organs. The approach to
      monitoring blood microcirculation using the contrast analysis of time-averaged
      speckle images is known as the laser speckle contrast analysis (LASCA) technique.
      This paper presents a modified version of LASCA, based on the application of a
      localized light source in combination with the speckle contrast analysis of time
      integrated dynamic speckle patterns. This method adds possibilities for the
      analysis of depth distributions of the blood microcirculation parameters. A
      theoretical background for the depth-resolved analysis of blood microcirculation
      parameters is considered here on the basis of the concept of effective optical
      path distributions for a multiply scattered probe light.

PMID- 12496037
TI  - Measurement of a velocity field in microvessels using a high resolution PIV
      technique.
AB  - Because endothelial cells are subject to flow shear stress, it is important to
      determine the velocity distribution in microvessels during studies of the
      mechanical interactions between the blood and the endothelium. Particle image
      velocimetry (PIV) is a quantitative method for measuring velocity fields
      instantaneously in experimental fluid mechanics. The authors have developed a
      high-resolution PIV technique that improves the dynamic flow range, spatial
      resolution, and measurement accuracy. The proposed method was applied to images
      of the arteriole in the rat mesentery, using an intravital microscope and high
      speed digital video system. Taking the mesentery motion into account, the PIV
      technique was improved to measure red blood cell (RBC) velocity. Velocity
      distributions with spatial resolutions of 0.8 3 0.8 mm were obtained even near
      the wall in the center plane of the arteriole. The arteriole velocity profile was
      blunt in the center region of the vessel cross-section and sharp in the near-wall
      region. Typical flow features for non-Newtonian fluid are shown.

PMID- 12496038
TI  - Biosimulation and visualization: effect of cerebrovascular geometry on
      hemodynamics.
AB  - Hemodynamics plays an important role in cardiovascular disorders, and the authors
      are applying numerical and experimental studies of cerebrovascular blood flow to
      the creation and rupture of cerebral aneurysms. In particular, this study aims to
      investigate the effects of cerebrovascular geometry on hemodynamics, such as flow
      pattern, wall shear stress distribution, and pressure. This report consists
      mainly of two parts: numerical study of blood flow in the artery extracted from
      computer tomography data, and numerical and experimental studies of a curved pipe
      model. The simulation was conducted by using a finite element method; the
      experiment was conducted by particle imaging velocimetry. Numerical and
      experimental results are compared and both show similar secondary flow behavior.

PMID- 12496039
TI  - Polymorphisms in DNA repair genes and associations with cancer risk.
AB  - Common polymorphisms in DNA repair genes may alter protein function and an
      individual's capacity to repair damaged DNA; deficits in repair capacity may lead
      to genetic instability and carcinogenesis. To establish our overall understanding
      of possible in vivo relationships between DNA repair polymorphisms and the
      development of cancer, we performed a literature review of epidemiological
      studies that assessed associations between such polymorphisms and risk of cancer.
      Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and
      XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for
      Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez).
      These studies focused on adult glioma, bladder cancer, breast cancer, esophageal
      cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma),
      squamous cell carcinoma of the head and neck, and stomach cancer. We found that a
      small proportion of the published studies were large and population-based.
      Nonetheless, published data were consistent with associations between: (a) the
      OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1
      R194W variant and reduced risk of various types of cancer; and (c) the BRCA2
      N372H variant and increased risk of breast cancer. Suggestive results were seen
      for polymorphisms in other genes; however, small sample sizes may have
      contributed to false-positive or false-negative findings. We conclude that large,
      well-designed studies of common polymorphisms in DNA repair genes are needed.
      Such studies may benefit from analysis of multiple genes or polymorphisms and
      from the consideration of relevant exposures that may influence the likelihood of
      cancer in the presence of reduced DNA repair capacity.

PMID- 12496040
TI  - Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review.
AB  - Endometrial cancer is a disease of the affluent, developed world, where
      epidemiological studies have shown that > or =40% of its incidence can be
      attributed to excess body weight. An additional proportion may be because of lack
      of physical activity. Alterations in endogenous hormone metabolism may provide
      the main links between endometrial cancer risk, and excess body weight and
      physical inactivity. Epidemiological studies have shown increased endometrial
      cancer risks among pre- and postmenopausal women who have elevated plasma
      androstenedione and testosterone, and among postmenopausal women who have
      increased levels of estrone and estradiol. Furthermore, there is evidence that
      chronic hyperinsulinemia is a risk factor. These relationships can all be
      interpreted in the light of the "unopposed estrogen" hypothesis, which proposes
      that endometrial cancer may develop as a result of the mitogenic effects of
      estrogens, when these are insufficiently counterbalanced by progesterone. In our
      overall synthesis, we conclude that development of ovarian hyperandrogenism may
      be a central mechanism relating nutritional lifestyle factors to endometrial
      cancer risk. In premenopausal women, ovarian hyperandrogenism likely increases
      risk by inducing chronic anovulation and progesterone deficiency. After the
      menopause, when progesterone synthesis has ceased altogether, excess weight may
      continue increasing risk through elevated plasma levels of androgen precursors,
      increasing estrogen levels through the aromatization of the androgens in adipose
      tissue. The ovarian androgen excess may be because of an interaction between
      obesity-related, chronic hyperinsulinemia with genetic factors predisposing to
      the development of ovarian hyperandrogenism.

PMID- 12496041
TI  - Why have we failed to find the low penetrance genetic constituents of common
      cancers?

PMID- 12496042
TI  - Point: myeloperoxidase -463G --> a polymorphism and lung cancer risk.
AB  - Myeloperoxidase (MPO) is released from neutrophils in lung tissue in response to
      exposure to various pulmonary insults, including tobacco smoking. This enzyme is
      involved in the activation of an intermediate metabolite of benzo(a)pyrene to the
      highly reactive benzo(a)pyrene diol epoxide. A (-463)G --> A polymorphism in the
      promoter region of the MPO gene has been identified. The A allele is associated
      with a decreased transcriptional activity attributable to the disruption of a SP1
      binding site. We therefore examined whether carriers of the A allele may be at
      reduced risk of lung cancer in a case-control study of 150 cases and 172 control
      individuals, all Caucasian smokers. Relative to subjects with the MPO G/G
      genotype, a significant decreased risk of lung cancer was found for carriers of
      the G/A genotype [odds ratio (OR) = 0.5, 95% confidence interval (CI): 0.29
      0.88]. A reduction in risk, although not statistically significant, was also
      observed for subjects with the A/A genotype (OR = 0.84, 95% CI: 0.31-2.32). The
      lung cancer risk for carriers of one or two copies of the A allele was 0.55 (95%
      CI: 0.33-0.93). Because of the low prevalence of the A/A genotype, we also
      performed a meta-analysis of 2686 lung cancer cases and 3325 controls. The
      summary OR suggested a slight protective effect of the A/A genotype (OR = 0.86,
      95% CI: 0.67-1.1), but this finding was strongly influenced by the results of a
      single large study. The meta-analysis restricted to studies comprising a
      homogeneous set yielded an OR of 0.68 (95% CI: 0.5-0.93). However, because of the
      heterogeneity in individual study results, additional large case-control studies
      are warranted to provide a more definitive conclusion.

PMID- 12496043
TI  - Counterpoint: the myeloperoxidase -463G-->a polymorphism does not decrease lung
      cancer susceptibility in Caucasians.
AB  - The myeloperoxidase (MPO) G-to-A substitution polymorphism in the promoter region
      of the MPO gene has been associated with a 40-70% reduction in lung cancer risk
      in several studies, although a recent nested case-control study disputes these
      findings. MPO is involved in the activation of a number of procarcinogens,
      including benzo(a)pyrene. The variant A allele has been shown to reduce MPO mRNA
      expression, thus potentially decreasing carcinogen activation. To confirm results
      from smaller studies, we evaluated this MPO polymorphism in 988 incident
      Caucasian lung cancer cases and 1128 controls. Logistic regression evaluated the
      association between MPO genotype and lung cancer risk, adjusting for age, gender,
      smoking status, time since quitting smoking, and pack-years of smoking. In the
      controls, the A allele frequency was 21%, and genotype distribution was in the
      Hardy-Weinberg equilibrium. Compared with the wild-type G/G genotype, the
      adjusted odds ratios for the A/A and A/G genotypes were 1.15 (95% confidence
      interval 0.7-1.9, P > 0.2) and 1.03 (95% confidence interval 0.8-1.3, P > 0.20),
      respectively. A similar lack of association was seen in analyses stratified by
      smoking status, median age, a number of smoking variables, disease stage, tumor
      grade, and histological subtype. These findings are in contrast with earlier
      studies suggesting a protective effect of carrying the variant A allele.

PMID- 12496044
TI  - Polychlorinated biphenyls, cytochrome P450 1A1, and breast cancer risk in the
      Nurses' Health Study.
AB  - There is concern that exposures to the environmental chemicals polychlorinated
      biphenyls (PCBs) may contribute to breast cancer risk. An individual's
      susceptibility to the effects of PCBs may be partially determined by
      polymorphisms in the gene encoding the biotransformation enzyme cytochrome P450
      1A1 (CYP1A1). PCB exposure induces CYP1A1 activity, and PCBs themselves or other
      xenobiotics can be metabolized to carcinogenic intermediates in the presence of
      the variant genotype. A previous case-control study provided evidence of an
      interaction between high exposures to PCBs and the CYP1A1-exon 7 polymorphism
      (the A to G transition at nucleotide 4889), leading to a significant increase in
      postmenopausal breast cancer risk. We examined the interaction of PCBs with the
      CYP1A1-MspI (the T to C transition at nucleotide 6235) and exon 7 polymorphisms
      among 367 breast cancer case-control pairs (293 postmenopausal pairs) in the
      Nurses' Health Study. Although there was no independent association of either the
      CYP1A1 variants or PCBs with breast cancer risk, the relative risk among the
      postmenopausal women with plasma PCB levels in the highest third of the
      distribution in the control group and at least one exon 7 variant allele compared
      with women who were homozygous for the wild-type allele and who had PCB levels in
      the lowest third was 2.78 (95% confidence interval, 0.99-7.82). The majority of
      studies have concluded that exposure to PCBs is unlikely to be a major cause of
      breast cancer, but these findings indicate that further studies of genetically
      susceptible populations are warranted.

PMID- 12496045
TI  - Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer.
AB  - Epidemiological evidence supports a role for the insulin-like growth factors
      (IGFs) and their binding proteins (IGFBPs) in the induction and progression of
      various cancers. Estrogen, which plays a role in the etiology of breast cancer,
      both regulates and is influenced by the IGF family. Risk of breast cancer
      associated with serum levels of IGF-I and/or IGFBPs may therefore depend upon
      menopausal status. A nested, case-control study was conducted on 66 women who
      were premenopausal and 60 who were postmenopausal at the time of diagnosis of
      primary breast cancer; they were selected from a cohort of 95,000 women who
      underwent multiphasic health check-ups > 30 years ago when enrolled in the Kaiser
      Permanente Medical Care Program. For each case, one control who matched by age,
      date of examination, and length of follow-up was chosen. Concentrations of IGF-I,
      insulin, glucose, and IGFBP-1, IGFBP-2, and IGFBP-3 in serum drawn at least 2
      years before diagnosis (mean times of 10.5 and 15.8 years for pre- and
      postmenopausal cases, respectively) were compared using conditional logistic
      regression analysis. All statistical tests were two-sided. Serum IGF-I, adjusted
      for insulin, glucose, and body mass index, was weakly associated with breast
      cancer risk across quartiles for premenopausal women only (P for trend = 0.05).
      Serum IGFBP-3 was higher in premenopausal cases versus controls (P = 0.04) and
      showed a positive trend in risk for increasing quartiles (P for trend = 0.033).
      After adjusting for insulin, glucose, body mass index, and IGF-I, premenopausal
      women in the highest quartile of IGFBP-3 had an elevated risk of breast cancer
      [odds ratio (OR) = 5.28, 95% confidence interval (CI) = 1.13-24.7]. Conversely,
      IGFBP-3 was lower in postmenopausal cases versus controls (P = 0.04) but showed
      no significant trend in risk. Postmenopausal women with glucose levels in the
      diabetic range were at increased risk for developing breast cancer (OR = 2.06,
      95% CI = 0.87-4.91), whereas those in the highest quartile of IGFBP-2 had a
      substantial reduction (71%) in risk relative to those in the lowest quartile (OR
      = 0.29, 95% CI = 0.09-0.92). Serum IGFBP-1 was not associated with breast cancer
      risk in either pre- or postmenopausal women. In premenopausal women, elevated
      serum IGF-I and IGFBP-3 are associated with increased breast cancer risk, whereas
      elevated serum IGFBP-2 is inversely associated with risk of postmenopausal breast
      cancer.

PMID- 12496046
TI  - Do thyroid disorders increase the risk of breast cancer?
AB  - The objective of this study was to determine whether thyroid disorders or
      treatment of such disorders affects the risk of breast cancer. Subjects aged 35
      64 years were participants in the National Institute of Child Health and Human
      Development Women's Contraceptive and Reproductive Experiences Study, a
      population-based, case-control study of invasive breast cancer that was carried
      out at five sites in the United States. In-person interviews were completed for
      4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682
      control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated using multiple logistic regression methods.
      Models included adjustment for age (5-year age groups), race (white or black),
      and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not
      associated with breast cancer risk. Only women with a history of thyroid cancer
      had an increased risk, but this was restricted to parous women (parous OR = 3.4,
      95% CI = 1.5-8.1; nulliparous OR = 0.5, 95% CI = 0.04-5.1). Breast cancer risk
      was not associated with treatment for thyroid disorders. There was no statistical
      interaction between thyroid disorders, thyroid treatments, and race, menopausal
      status, or parity. We found no association between thyroid disorders or their
      associated treatments and the risk of breast cancer.

PMID- 12496047
TI  - Psychosocial predictors of BRCA counseling and testing decisions among urban
      African-American women.
AB  - Genetic counseling and testing for mutations in XXX (BRCA)1/2 genes that increase
      breast cancer susceptibility potentially offer a number of benefits (e.g., more
      informed decision making regarding breast cancer prevention options) but also
      raise potential problems (e.g., issues of discrimination). However, the
      literature suggests that African-American women underuse genetics-related
      services. Therefore, the primary aim of the current study was to investigate
      predictors of the use of genetic counseling and testing for breast cancer
      susceptibility in this population. Participants were 76 African-Americans at
      increased risk for breast cancer attributable to their family history of the
      disease. Participants were recruited from an urban cancer screening clinic and
      completed measures assessing sociodemographic information, breast cancer
      knowledge, breast cancer-specific emotional distress, and perceived benefits of
      and barriers to BRCA testing. Free BRCA counseling and testing were offered to
      all interested participants, and measures were completed before counseling
      sessions. On the basis of their subsequent acceptance or refusal of these
      services, participants were described as having either: (a) declined BRCA-related
      genetic counseling (GC-); (b) participated in genetic counseling but refused
      genetic testing (GC+GT-); or (c) participated in both genetic counseling and
      testing (GC+GT+). Results revealed that participants who declined counseling had
      significantly less knowledge of breast cancer genetics than those who accepted
      both counseling and testing. No differences emerged among the three groups in
      terms of perceived benefits of testing. However, participants declining
      counseling demonstrated significantly higher perceived barrier scores compared
      with those accepting counseling and testing. Specifically, those who did not
      participate in counseling reported greater anticipation of negative emotional
      responses to testing and more concern about stigmatization, whereas those who
      underwent both counseling and testing had significantly lower family-related
      guilt. Finally, cancer-specific distress was positively associated with
      participation in counseling, regardless of participation in testing. The current
      findings underscore the need for refinement of outreach and intervention efforts
      that both increase awareness of BRCA counseling and testing among African
      American women and provide information to those considering these options.

PMID- 12496048
TI  - Association of aspirin and nonsteroidal anti-inflammatory drug use with breast
      cancer.
AB  - OBJECTIVE: Previous epidemiological studies have suggested that use of aspirin or
      other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with
      reduced risk of breast cancer, but some studies have been limited in their
      ability to separate the effects of aspirin from other NSAIDs or to account for
      breast cancer risk factors. METHODS: We examined the incidence of breast cancer
      in association with self-reported aspirin, as well as other nonaspirin NSAID use
      in a large prospective cohort of postmenopausal women (n = 27,616). Over 6 years
      of follow-up, 938 incident breast cancers were identified. RESULTS: After
      adjustment for other breast cancer risk factors, any current use of aspirin or
      other NSAIDs compared with no use was associated with a reduction in risk of
      breast cancer [relative risk (RR) = 0.80, 95% confidence interval (CI) 0.67
      0.95]. There was a trend of decreasing risk of incident breast cancer with
      increasing frequency of aspirin use (P(trend) = 0.0011). The multivariate
      adjusted RR of breast cancer was 0.71 (95% CI 0.58-0.87) for women who reported
      using aspirin six or more times per week compared with women who reported no use.
      These results did not depend on whether women had early or late stage breast
      cancer. No association was found between nonaspirin NSAID use and incident breast
      cancer. The adjusted RR of using other NSAIDs six or more times per week compared
      with no use was 1.01 (95% CI 0.83-1.25). CONCLUSION: This prospective study
      corroborates other reports that use of aspirin might reduce risk of breast
      cancer.

PMID- 12496049
TI  - Detection of 2,6-cyclolycopene-1,5-diol in breast nipple aspirate fluids and
      plasma: a potential marker of oxidative stress.
AB  - An high-performance liquid chromatography method with electrochemical detection
      was developed to quantify both 2,6-cyclolycopene-1,5-diol and lycopene in plasma
      and breast nipple aspirate fluids (NAF). As an example of the utility of this
      assay, levels in plasma and NAF of 11 women were examined and compared with
      levels of 8-isoprostane, a commonly used marker of lipid oxidation. Levels of 2,6
      cyclolycopene-1,5-diol and 8-isoprostane were higher in NAF than in plasma, but
      levels of lycopene were lower in NAF than in plasma. Levels of 2,6-cyclolycopene
      1,5-diol in plasma and in NAF were significantly correlated with both lycopene
      and 8-isoprostane levels. This is consistent with the dependence of 2,6
      cyclolycopene-1,5-diol levels on both dietary intakes of lycopene and oxidative
      stress levels. For the correlations between NAF and plasma, lycopene levels were
      significantly correlated, whereas 2,6-cyclolycopene-1,5-diol levels were not,
      indicating that levels of 2,6-cyclolycopene-1,5-diol in NAF are difficult to
      predict from plasma levels. The high levels of 2,6-cyclolycopene-1,5-diol and 8
      isoprostane in NAF are consistent with high levels of oxidative stress in the
      breast.

PMID- 12496050
TI  - Effects of a 9-month strength training intervention on insulin, insulin-like
      growth factor (IGF)-I, IGF-binding protein (IGFBP)-1, and IGFBP-3 in 30-50-year
      old women.
AB  - We assessed the effects of twice weekly strength training on several proposed
      risk factors for breast and colon cancer: body fat, waist circumference, fasting
      insulin, fasting glucose, insulin-like growth factor I (IGF-I), and several IGF
      binding proteins. Fifty-four healthy women, 30-50 years old, were randomized to
      no-contact control or treatment: 15 weeks of supervised strength training
      followed by 6 months of unsupervised training. Fifteen-week changes included
      reductions in percentage of body fat, fasting insulin, fasting glucose, and IGF-I
      that were larger in the treatment than control participants (treatment versus
      control mean +/- SE: % body fat -1.97 +/- 0.42 versus -0.43 +/- 0.40, P = 0.01;
      insulin (uU/ml) -0.29 +/- 0.35 versus 0.81 +/- 0.38, P = 0.055; glucose (mg/dl) 
      1.92 +/- 1.27 versus 1.21 +/- 1.36, P = 0.13; and IGF-I (ng/ml) -30.47 +/- 9.75
      versus 5.86 +/- 10.44, P = 0.02). There was no treatment effect on IGF-binding
      proteins 1 and 3 or either of two surrogate measures of free IGF-I. By 39 weeks
      changes in percentages of body fat were largely maintained; IGF-I returned to
      baseline levels in the treatment group but remained 15% lower in treatment
      compared with control participants. Strength training produced favorable changes
      in several proposed cancer risk factors. The importance of these changes to long
      term cancer prognosis, diagnosis, and/or recurrence remains to be determined.

PMID- 12496051
TI  - Biologic correlates of a biochemoprevention trial in advanced upper aerodigestive
      tract premalignant lesions.
AB  - OBJECTIVE: To identify tissue biomarkers that might be used to assess an
      individual's cancer risk and response to chemoprevention, we studied in
      dysplastic lesions of the larynx and the p.o. cavity, a series of biomarkers
      extensively used in previous chemoprevention trials, including chromosome
      polysomy (CP), proliferative status, p53 expression and gene mutations, and loss
      of heterozygosity at 9p, 3p, and 17p. METHOD: Biopsies from 32 participants in a
      prospective chemoprevention trial using 13-cis-retinoic acid, IFN-alpha, and
      alpha-tocopherol for 12 months (20 with vocal cord and 12 with p.o. cavity
      lesions) were analyzed for p53 and Ki-67 expression by immunohistochemistry, loss
      of heterozygosity by PCR amplification, p53 mutations by PCR-based direct
      sequencing, and CP by in situ hybridization. RESULTS: High CP (> or =4% cells
      with more than three chromosome copies per nucleus) was more common in p.o. (8 of
      10) than laryngeal lesions (4 of 16; P = 0.01), and so was a combination of CP >
      or = 4% and parabasal layer p53 labeling index > or = 0.2 (P = 0.02). Low CP was
      a significant predictor of complete histological response (8 of 14 cases with low
      versus 1 of 12 cases with high CP; P = 0.01). A trend for histological
      progression or cancer development was observed in cases with high CP and
      parabasal layer p53 labeling index. CONCLUSION: Low CP, more frequently observed
      in laryngeal lesions, appears to be a predictor of response to chemoprevention
      and could be used as a screening tool to identify suitable candidates for such
      approaches. Further investigation of biological parameters of response and cancer
      risk is warranted.

PMID- 12496052
TI  - 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and
      colon cancer in African Americans and whites.
AB  - We evaluated polymorphisms in methylenetetrahydrofolate reductase (MTHFR), folate
      intake and alcohol consumption in relation to risk of colon cancer in a
      population-based case-control study in North Carolina. The study included 555
      cases (244 African Americans and 311 whites) and 875 controls (331 African
      Americans and 544 whites). Total folate intake of <400 versus > or =400
      microg/day showed a weak positive association with colon cancer among both
      African Americans [adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) =
      1.0-2.0] and whites (OR = 1.6, 95% CI = 1.2-2.2). No association was observed
      with use of alcohol. Compared with wild-type genotypes, there was no association
      between the low activity MTHFR codon 677 TT genotype and colon cancer, but the
      low activity codon 1298 CC genotype was inversely associated with colon cancer in
      whites (OR = 0.5, 95% CI = 0.3-0.9). Unlike previous studies, we did not observe
      a strong protective effect of the codon 677 TT low-activity genotype when folate
      intake was high. Instead, we observed an increased risk of colon cancer when
      folate intake was low for participants with wild- type genotypes. Adjusted ORs
      for the combined effects of codon 677 CC and codon 1298 AA genotypes and folate
      intake <400 microg/day were 1.9 (95% CI = 1.1-3.4) in African Americans and 2.5
      (95% CI = 1.2-5.2) in whites. Our results suggest that variation at MTHFR codon
      1298 (within the COOH-terminal region) may be more important for colon cancer
      than variation at codon 677 (NH(2)-terminal region), and in populations where
      folate intake is low, wild-type MTHFR activity may increase risk for colon
      cancer.

PMID- 12496053
TI  - Semiquantitation of polycyclic aromatic hydrocarbon-DNA adducts in human
      esophagus by immunohistochemistry and the automated cellular imaging system.
AB  - It has been suggested that ingestion of polycyclic aromatic hydrocarbons (PAHs)
      may contribute to the high incidence and mortality of esophageal cancer in
      Linxian, China. To explore this relationship a semiquantitative
      immunohistochemical staining method was developed for localization of PAH-DNA
      adducts. Nuclear color intensity (bright field average pink intensity per nucleus
      for >1000 cells) was measured using the ChromaVision Automated Cellular Imaging
      System (ACIS). Paraffin-embedded sections of cultured human keratinocytes exposed
      to increasing concentrations of 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy
      7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) were incubated with BPDE-DNA antiserum
      and served as an internal positive control (standard curve). Values for nuclear
      staining intensity correlated directly with BPDE exposure concentration (r(2) =
      0.99) and were reproducible. DNA adduct levels determined by BPDE-DNA
      chemiluminescence immunoassay in DNA from BPDE-exposed keratinocytes, correlated
      with BPDE exposure concentrations (r(2) = 0.99), showing that nuclear staining
      intensity determined by ACIS correlated directly with BPDE-DNA adduct levels
      determined by chemiluminescence immunoassay. The ACIS methodology was applied to
      5 human samples from Linxian, and significantly positive nuclear PAH-DNA adduct
      staining was observed in this group when compared with esophageal tissue from 4
      laboratory-housed monkey controls and 6 samples obtained at autopsy from smokers
      and nonsmokers in the United States. Nuclear PAH-DNA staining was absent from
      Linxian samples when serial sections were incubated with normal rabbit serum
      (negative control) and was significantly reduced on incubation with BPDE-DNA
      antiserum absorbed previously with the immunogen BPDE-DNA. These results appear
      to support the hypothesis that high PAH exposure levels may be etiologically
      associated with the development of esophageal cancer in Linxian.

PMID- 12496054
TI  - Plasma 7beta-hydroxycholesterol as a possible predictor of lung cancer risk.
AB  - Epidemiological data suggests a role of dietary cholesterol in the etiology of
      lung cancer without having a clear biological hypothesis. Although smoking as the
      outstanding risk factor for lung cancer may enhance lipid peroxidation reactions,
      this study was planned to assess smoking-independent associations between the
      extent of cholesterol oxidation and the risk for lung cancer. In the frame of a
      nested case-control study in European Prospective Investigation on Cancer
      Heidelberg, six cholesterol oxidation products (COPs) were determined in plasma
      samples of 20 incident lung cancer patients obtained 1.9 +/- 0.6 years before
      diagnosis and in 40 matched (including smoking habits) controls. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic
      regression. Among all COP compounds tested, plasma 7beta-hydroxycholesterol was
      associated with lung cancer risk. The high crude risk estimate (OR approximately
      equals 5) became significant after adjustment for sports activity (OR = 6.83, CI
      = 1.08-43.01, 3rd versus 1st tertile). For the independent effect of 7beta
      hydroxycholesterol, i.e., adjusted for other COP compounds, an OR of 8.08 (CI =
      1.12-58.54, 3rd versus 1st tertile) was calculated (P = 0.04 for trend). Lung
      cancer risk adjusted for sports activity significantly increased by 26% (CI =
      1.050-1.506, P = 0.01) per unit (1 nmol/mmol plasma cholesterol) of 7beta
      hydroxycholesterol. No dietary factor had a significant effect in the regression
      model, but the dietary intake of meat, eggs, animal fat, cholesterol, and fruits
      (inversely) correlated with plasma COP concentrations. In this small study,
      plasma 7beta-hydroxycholesterol appeared to be a smoking-independent predictor of
      lung cancer risk and might therefore be used as a biomarker. Because of the
      rather high-risk estimate, research on possible intrinsic biological effects of
      this compound should be encouraged.

PMID- 12496055
TI  - Attributable risks of familial cancer from the Family-Cancer Database.
AB  - Population attributable faction (PAF) shows the proportion of the disease that
      could be prevented if the cause could be removed. PAFs for most types of familial
      cancer have not been determined. We used the Swedish Family-Cancer Database on
      10.2 million individuals and 688,537 parental and 116,741 offspring cancers to
      calculate familial risks, proportions of affected individuals, and familial PAFs
      for 28 neoplasms among 0-66-year-old offspring. The data were calculated by an
      exact proband status in the nuclear families. The familial risks for offspring
      cancer were increased at 23 of 28 sites from the same cancer in only the parent,
      at 17 sites from a sibling proband and at 12 sites from a parent and sibling
      proband. The highest PAFs by parent were for prostate (9.01%), breast (3.67%),
      and colorectal (5.15%) cancer. However, considering that in gender-specific
      cancers, the familial effect may originate from grandparents, the PAFs for
      prostate and breast cancer could be multiplied by 2. The PAFs for the sibling
      history of prostate, breast, and colorectal cancers were 1.55, 2.85, and 1.23%
      and for the parent and sibling history 0.99, 0.42, and 0.48%, respectively.
      Because of mutually exclusive proband definition, the PAFs were additive, giving
      a total PAF of 20.55% for prostate, 10.61% for breast, and 6.87% for colorectal
      cancer. The present PAF values give an estimate of the heritable single locus or
      additive effects for cancer in nuclear families. The data show that the familial
      PAF of prostate cancer was 20.55%, and breast cancer 10.61%, but for most other
      sites, it was between 1 and 3%.

PMID- 12496056
TI  - Inhibitory effects of sodium salicylate and acetylsalicylic acid on UVB-induced
      mouse skin carcinogenesis.
AB  - We conducted an in vivo carcinogenesis experiment to determine the efficacy of
      topical aspirin and sodium salicylate (NAS) in preventing UVB-induced nonmelanoma
      skin cancer. Hairless SKH-1 mice were randomly divided into eight treatment
      groups. They were treated topically with either 40 or 10 micromol aspirin or NAS
      three times weekly before 9 kJ/m(2) UVB irradiation. The experiment was carried
      out over 25 weeks. Both dose levels of NAS significantly inhibited (P < 0.05) the
      rate of tumor formation when compared with vehicle control. The 40 micromol dose
      of aspirin significantly inhibited the rate of tumor formation (P < 0.05),
      whereas the 10 micromol dose had no inhibitory effect when compared with the
      vehicle control. To investigate the mechanism of this inhibition, we studied UVB
      induced thymine dimer formation in the epidermis of the mouse skin. We found that
      NAS inhibited UVB-induced thymine dimer formation (P = 0.0001), whereas aspirin
      did not. Therefore, we conclude that NAS prevents UVB-induced tumor growth and
      formation through a sunscreen effect; whereas, the moderate inhibition of aspirin
      may be because of a molecular event, such as the inhibition of various UVB
      signaling pathways.

PMID- 12496057
TI  - Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the
      rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.
AB  - We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated
      analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the
      azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and
      aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using
      these biomarkers, in this study we examined the anticarcinogenic mechanisms of
      these chemopreventive agents. Rats were maintained on AIN-76A chow or
      supplemented with 0.4% UDCA or F(6)-D(3) (2.5 nmol/kg chow) and treated weekly
      with AOM 20 mg i.p./kg wt or saline x 2 weeks. F(6)-D(3) was continued for an
      additional 2 weeks and UDCA for the duration of the study. At 40 weeks, animals
      received bromodeoxyuridine (BrdUrd) i.p. 2 h before sacrifice. A portion of each
      tumor was fixed in formalin and the remainder flash frozen. Colons were divided
      longitudinally and half-fixed in formalin and half in ethanol. The size and
      location of methylene blue-stained ACF were recorded. Cell proliferation (BrdUrd
      labeling) and apoptosis (terminal deoxynucleotidyl transferase-mediated nick end
      labeling assay) were measured in colonic crypts and tumors. Protein expression
      levels of several regulators of cell proliferation were analyzed by
      immunostaining and Western blotting. Colonic crypt cyclin D1 and E-cadherin mRNA
      levels were measured by real-time PCR. In saline injected controls, neither UDCA
      nor F(6)-D(3) alone had any effect on cytokinetic parameters or on the expression
      of mitogenic regulators. AOM significantly increased the proliferation
      (percentage of BrdUrd-positive cells) of both ACF (23.1 +/- 1.7%) and non-ACF
      crypts (17.6 +/- 1.6%), compared with normal colonic crypts (4.5 +/- 0.8%; P <
      0.05). This hyperproliferation was accompanied by a 5-fold increase in cyclin D1
      and >50% decrease in E-cadherin protein (P < 0.05) in ACF, both of which are
      predicted to be growth-enhancing alterations. UDCA and F(6)-D(3) significantly (P
      < 0.05) inhibited AOM-induced crypt cell hyperproliferation, ACF development, and
      tumor burden. These chemopreventive agents also significantly blocked AOM-induced
      alterations in cyclin D1 and E-cadherin protein in ACF and tumors. In ACF,
      changes in mRNA levels of cyclin D1, but not E-cadherin, paralleled alterations
      in protein expression. Cyclooxygenase-2 and inducible nitric oxide synthase were
      increased in AOM tumors but not in ACF, and these changes were blocked by UDCA
      and F(6)-D(3). UDCA and F(6)-D(3) significantly inhibited ACF development and
      hyperproliferation, in part, by preventing carcinogen-induced alterations in
      cyclin D1 and E-cadherin. In established tumors, UDCA and F(6)-D(3) also limited
      inductions of cyclooxygenase-2 and inducible nitric oxide synthase, which
      together with their effects on cyclin D1 and E-cadherin, contribute to their
      chemopreventive actions.

PMID- 12496058
TI  - Effects of tea on preneoplastic lesions and cell cycle regulators in rat liver.
AB  - The effects of tea polyphenols and tea pigments on rat liver precancerous lesions
      and some cell cycle regulators were studied. A modified Solt-Farber model in rats
      was established by multiple low-dosage of N-nitrosodiethylamine (NDEA) i.p.
      injections, followed by i.p. CCl(4) injection and partial hepatectomy. Sixty male
      Wistar rats were randomly divided into four groups: positive control group, two
      tea-treated groups, and negative control group. Rats in tea-treated groups were
      given tea polyphenols (0.1%) and tea pigments (0.1%) in drinking fluid during the
      whole experiment. The number and area of glutathione S-transferase P (GST-P)
      positive foci in the rat liver were used as biomarkers of precancerous liver
      lesions. Western blotting assay was carried out to detect the expression of
      cyclin D1, CDK4, and P21(WAF1/CIP1) on whole liver extract. At the end of the
      experiment (56 days), the number and area of GST-P-positive foci in liver
      increased significantly in carcinogen-administered positive control group,
      whereas no GST-P-positive foci were found in the negative control group in which
      animals did not receive carcinogen exposure. The number and area of GST-P
      positive foci in tea-treated, carcinogen-exposed groups were significantly
      reduced as compared with the positive control group. It was also found that the
      expression of P21(WAF1/CIP1) was significantly induced and the expression of
      cyclin D1 and CDK4 was significantly inhibited in tea-treated groups. These
      results suggest that tea polyphenols and tea pigments are effective in preventing
      the precancerous liver lesions in rats, and modulation of cell cycle by
      regulating cell cycle regulators may be a possible mechanism.

PMID- 12496059
TI  - Anabasine and anatabine as biomarkers for tobacco use during nicotine replacement
      therapy.
AB  - In this study we determined urine concentration of the tobacco alkaloids
      anabasine and anatabine, nicotine and its metabolites cotinine, and nornicotine
      in 99 cigarette smokers and 205 smokeless tobacco users. We also investigated the
      possibility that anabasine and anatabine can be used as biomarkers for tobacco
      use during nicotine replacement therapy. Urine samples and data on self-reported
      tobacco use were obtained from subjects enrolled in tobacco cessation programs.
      Urine concentrations of tobacco alkaloids and metabolites were measured and
      correlated with self-reported tobacco use. Concentrations of anabasine and
      anatabine were used to validate abstinence in smokeless tobacco users who used
      nicotine gum as part of the therapy. Correlations of alkaloid concentration with
      self-reported tobacco use before treatment ranged from fair to poor. In subjects
      abstaining from smokeless tobacco but using nicotine gum, anabasine and anatabine
      levels were below the cut-point of 2 ng/ml despite high concentrations of
      nicotine and cotinine resulting from nicotine gum use. Anabasine and anatabine
      concentrations in urine can be used to validate abstinence or measure the extent
      of tobacco use in persons undergoing nicotine replacement therapy.

PMID- 12496060
TI  - Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health
      Study.
AB  - The association between soyfood consumption and subsequent bladder cancer risk
      was investigated in a population-based cohort study, the Singapore Chinese Health
      Study. As of December 31, 2000, 329,848 person-years of follow-up were accrued.
      Sixty-one histologically confirmed incident bladder cancer cases were identified.
      Information on soyfood consumption at baseline was obtained through in-person
      interviews using a validated dietary questionnaire. Relative risks and 95%
      confidence intervals were calculated using the Cox proportional hazard regression
      method. High intake of soyfood was statistically significantly related to an
      elevated risk of bladder cancer. Relative to the lowest quartile of energy
      adjusted total soy intake (<36.9 g/1000 Kcal), the highest quartile of total soy
      intake (> or =92.5 g/1000 Kcal) was associated with a 2.3-fold increase in
      bladder cancer risk (95% confidence interval = 1.1-5.1) after adjustment for
      cigarette smoking and level of education. Similar results were obtained for
      intakes of soy protein and soy isoflavones. The soyfood-bladder cancer risk
      association did not differ significantly between men and women and was not
      explained by other dietary factors. The soy-cancer relationship became stronger
      when the analysis was restricted to subjects with longer (> or =3 years) duration
      of follow-up. To our knowledge, this is the first epidemiological report on the
      effect of dietary soy on bladder cancer risk.

PMID- 12496061
TI  - Interactive effect of chemical substances and occupational electromagnetic field
      exposure on the risk of gliomas and meningiomas in Swedish men.
AB  - The objective of our study was to investigate the possible interactive effect of
      occupational exposure to extremely low-frequency magnetic field (ELFMF) and to
      known or suspected carcinogenic chemicals on the incidence of the two main
      histological types of brain cancer, gliomas and meningiomas, in a cohort of male
      Swedish workers. The historical cohort of all Swedish men gainfully employed in
      1970 were followed 19 years (1971-1989). Exposure to ELFMF and to nine chemicals
      were assessed using two Swedish job exposure matrices based on occupational codes
      and industrial activity. Relative risks adjusted for age, period, geographical
      area, and town size were computed using log-linear Poisson models. The main
      finding was the absence of ELFMF effect on glioma risk in the absence of a
      simultaneous exposure to chemical products. The effect of petroleum products was
      independent of the intensity of ELFMF exposure whereas solvents, lead, and
      pesticides/herbicides were only associated with glioma in workers also exposed to
      moderate or high levels of ELFMF. On the other hand, whereas ELFMF seemed to
      enhance the effect of specific chemicals in the causation of gliomas, we did not
      find a relationship between ELFMF exposure and meningiomas. The potential for
      ELFMF to act as an effect modifier of the association of chemical agents and
      glioma is an interesting new finding. It would be worthwhile to evaluate this
      hypothesis for other tumors. Also, it is necessary to confirm these results in
      epidemiological studies with individual exposure assessments, and in experimental
      studies that may elucidate whether there is a true causal mechanism for the
      results we observed.

PMID- 12496062
TI  - The TP53 codon 72 polymorphism may affect the function of TP53 mutations in
      breast carcinomas but not in colorectal carcinomas.
AB  - An Arg/Pro polymorphism in codon 72 of the TP53 gene was analyzed in blood
      samples from 390 breast and 162 colorectal cancer patients previously
      investigated for TP53 mutations in their tumors. Among the breast cancer cases,
      228 were homozygous for the Arg72 allele, of which, 65 (28.5%) also had a TP53
      mutation in their tumors. In contrast, of 26 cases that were homozygous for the
      Pro72 allele, only 1 case (3.8%) had a TP53 mutation in the tumor (P = 0.004).
      Cloning the TP53 gene from tumor DNA followed by sequencing was performed in 14
      heterozygotes with tumor mutation, and 9 of the mutations resided on the Arg72
      allele. Among the colorectal cancer cases, no difference in mutation frequency
      was seen between the two different homozygotes, 40 TP53 mutations in 97 Arg72
      homozygous cases (41.2%) versus 7 in 16 Pro72 homozygous cases (43.8%). These
      results suggest a selective growth advantage for cells carrying a type of TP53
      mutation seen in breast carcinomas when the mutation resides on an Arg72 allele.

PMID- 12496063
TI  - Induction of apoptosis in low to moderate-grade human prostate carcinoma by red
      clover-derived dietary isoflavones.
AB  - Epidemiological evidence suggests a geographical basis for the incidence of
      prostate cancer and dietary factors, including isoflavone consumption, may be
      linked to this phenomenon. This paper reports a nonrandomized, nonblinded trial
      with historically matched controls from archival tissue designed to determine the
      effects of acute exposure to a dietary supplement of isoflavones in men with
      clinically significant prostate cancer before radical prostatectomy. Thirty-eight
      patients were recruited to the study upon diagnosis of prostate cancer. Before
      surgery, 20 men consumed 160 mg/day of red clover-derived dietary isoflavones,
      containing a mixture of genistein, daidzein, formononetin, and biochanin A. Serum
      PSA, testosterone, and biochemical factors were measured, and clinical and
      pathological parameters were recorded. The incidence of apoptosis in prostate
      tumor cells from radical prostatectomy specimens was compared between 18 treated
      and 18 untreated control tissues. There were no significant differences between
      pre- and posttreatment serum PSA, Gleason score, serum testosterone, or
      biochemical factors in the treated patients (P > 0.05). Apoptosis in radical
      prostatectomy specimens from treated patients was significantly higher than in
      control subjects (P = 0.0018), specifically in regions of low to moderate-grade
      cancer (Gleason grade 1-3). No adverse events related to the treatment were
      reported. This report suggests that dietary isoflavones may halt the progression
      of prostate cancer by inducing apoptosis in low to moderate-grade tumors,
      potentially contributing to the lower incidence of clinically significant disease
      in Asian men. The assessment of new prostatic therapies aimed at increasing
      apoptosis should control for intake of dietary isoflavones.

PMID- 12496064
TI  - Microsomal epoxide hydrolase variants are not associated with risk of breast
      cancer.

PMID- 12496065
TI  - Modeling of the P700+ charge recombination kinetics with phylloquinone and
      plastoquinone-9 in the A1 site of photosystem I.
AB  - Light activation of photosystem I (PS I) induces electron transfer from the
      excited primary electron donor P700 (a special pair of chlorophyll a/a'
      molecules) to three iron-sulfur clusters, F(X), F(A), and F(B) via acceptors A(0)
      (a monomeric chlorophyll a) and A(1) (phylloquinone). PS I complexes isolated
      from menA and menB mutants contain plastoquinone-9 rather than phylloquinone in
      the A(1) site and show altered rates of forward electron transfer from A to
      [F(A)/F(B)] and altered rates of back electron transfer from [F(A)/F(B)](-) to
      P700+ (Semenov, A. Y., et al., J. Biol. Chem. 275:23429-23438, 2000). To identify
      the modified electron transfer steps, we studied the kinetics of flash-induced
      P700+ reduction in PS I that contains either an intact set or a subset of iron
      sulfur clusters F(X), F(A), and F(B) and with the A(1) binding site occupied by
      phylloquinone or plastoquinone-9. A modeling of the forward and backward electron
      transfer kinetics in P700-F(A)/F(B) complexes, P700-F(X) cores, and P700-A(1)
      cores shows that the replacement of phylloquinone by plastoquinone-9 induces a
      decrease in the free energy gap between A(1) and F(A)/F(B) from approximately 
      205 mV in wild-type PS I to approximately -70 mV in menA PS I. The +135 mV
      increase in the midpoint potential of A(1) explains the acceleration in the rate
      of P700+ dark reduction in menA PS I, and the resulting uphill electron transfer
      from A(1) to F(X) in menA PS I explains the absence of a contribution from F to
      the reduction of P700+. This fully quantitative description of PS I relates
      electron transfer rates, equilibrium constants, and redox potentials, and can be
      used to predict changes in these parameters upon substitution of electron
      transfer cofactors.

PMID- 12496066
TI  - The many-body problem for anisotropic membrane inclusions and the self-assembly
      of "saddle" defects into an "egg carton".
AB  - We calculate the many-body, nonpairwise interaction between N rigid, anisotropic
      membrane inclusions by modeling them as point-like constraints on the membrane's
      curvature tensor and by minimizing the membrane's curvature energy. Because
      multipolar distortions of higher-order decay on very short distances, our
      calculation gives the correct elastic interaction energy for inclusions separated
      by distances of the order of several times their size. As an application, we show
      by thermally equilibrating the many-body elastic energy using a Monte Carlo
      algorithm, that inclusions shaped as "saddles" attract each other and build an
      "egg-carton" structure. The latter is reminiscent of some patterns observed in
      membranes obtained from biological extracts, the origin of which is still
      mysterious.

PMID- 12496067
TI  - Molecular dynamics simulations of a hydrated protein vectorially oriented on
      polar and nonpolar soft surfaces.
AB  - We present a collection of molecular dynamics computer simulation studies on a
      model protein-membrane system, namely a cytochrome c monolayer attached to an
      organic self-assembled monolayer (SAM). Modifications of the system are explored,
      including the polarity of the SAM endgroups, the amount of water present for
      hydration, and the coordination number of the heme iron atom. Various structural
      parameters are measured, e.g., the protein radius of gyration and eccentricity,
      the deviation of the protein backbone from the x-ray crystal structure, the
      orientation of the protein relative to the SAM surface, and the profile
      structures of the SAM, protein, and water. The polar SAM appears to interact more
      strongly with the protein than does the nonpolar SAM. Increased hydration of the
      system tends to reduce the effects of other parameters. The choice of iron
      coordination model has a significant effect on the protein structure and the heme
      orientation. The overall protein structure is largely conserved, except at each
      end of the sequence and in one loop region. The SAM structure is only perturbed
      in the region of its direct contact with the protein. Our calculations are in
      reasonably good agreement with experimental measurements (polarized optical
      absorption/emission spectroscopy, x-ray interferometry, and neutron
      interferometry).

PMID- 12496068
TI  - An integrative model of the cardiac ventricular myocyte incorporating local
      control of Ca2+ release.
AB  - The local control theory of excitation-contraction (EC) coupling in cardiac
      muscle asserts that L-type Ca(2+) current tightly controls Ca(2+) release from
      the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type
      Ca(2+) channels (LCCs) and ryanodine receptors (RyRs). These local interactions
      give rise to smoothly graded Ca(2+)-induced Ca(2+) release (CICR), which exhibits
      high gain. In this study we present a biophysically detailed model of the normal
      canine ventricular myocyte that conforms to local control theory. The model
      formulation incorporates details of microscopic EC coupling properties in the
      form of Ca(2+) release units (CaRUs) in which individual sarcolemmal LCCs
      interact in a stochastic manner with nearby RyRs in localized regions where
      junctional SR membrane and transverse-tubular membrane are in close proximity.
      The CaRUs are embedded within and interact with the global systems of the myocyte
      describing ionic and membrane pump/exchanger currents, SR Ca(2+) uptake, and time
      varying cytosolic ion concentrations to form a model of the cardiac action
      potential (AP). The model can reproduce both the detailed properties of EC
      coupling, such as variable gain and graded SR Ca(2+) release, and whole-cell
      phenomena, such as modulation of AP duration by SR Ca(2+) release. Simulations
      indicate that the local control paradigm predicts stable APs when the L-type
      Ca(2+) current is adjusted in accord with the balance between voltage- and Ca(2+)
      dependent inactivation processes as measured experimentally, a scenario where
      common pool models become unstable. The local control myocyte model provides a
      means for studying the interrelationship between microscopic and macroscopic
      behaviors in a manner that would not be possible in experiments.

PMID- 12496070
TI  - Structure and energy of fusion stalks: the role of membrane edges.
AB  - Fusion of lipid bilayers proceeds via a sequence of distinct structural
      transformations. Its early stage involves a localized, hemifused intermediate in
      which the proximal but not yet the distal monolayers are connected. Whereas the
      so-called stalk model most successfully accounts for the properties of the
      hemifused intermediate, there is still uncertainty about its microscopic
      structure and energy. We reanalyze fusion stalks using the theory of membrane
      elasticity. In our calculations, a short (cylindrical micelle-like) tether
      connects the two proximal monolayers of the hemifused membranes. The shape of the
      stalk and the length of the tether are calculated such as to minimize the overall
      free energy and to avoid the formation of voids within the hydrocarbon core. Our
      free energy expression is based on three internal degrees of freedom of a
      perturbed lipid layer: thickness, splay, and tilt deformations. Based on exactly
      the same model, we compare fusion stalks with and without the ability included to
      form sharp edges at the interfacial region between the hydrocarbon core and the
      polar environment. Requiring the interface to be smooth everywhere, our detailed
      calculations recover previous results: the stalk energies are far too high to
      account for the experimental observation of fusion intermediates. However, if we
      allow the interface to be nonsmooth, we find a remarkable reduction of the stalk
      free energy down to more realistic values. The corresponding structure of a
      nonsmooth stalk exhibits sharp edges at the transition regions between the
      bilayer and tether parts. In addition to that, a corner is formed at each of the
      two distal monolayers. We discuss the mechanism how membrane edges reduce the
      energy of fusion stalks.

PMID- 12496069
TI  - Differences in electrostatic properties at antibody-antigen binding sites:
      implications for specificity and cross-reactivity.
AB  - Antibodies HyHEL8, HyHEL10, and HyHEL26 (HH8, HH10, and HH26, respectively)
      recognize highly overlapping epitopes on hen egg-white lysozyme (HEL) with
      similar affinities, but with different specificities. HH8 binding to HEL is least
      sensitive toward mutations in the epitope and thus is most cross-reactive, HH26
      is most sensitive, whereas the sensitivity of HH10 lies in between HH8 and HH26.
      Here we have investigated intra- and intermolecular interactions in three
      antibody-protein complexes: theoretical models of HH8-HEL and HH26-HEL complexes,
      and the x-ray crystal structure of HH10-HEL complex. Our results show that HH8
      HEL has the lowest number and HH26-HEL has the highest number of intra- and
      intermolecular hydrogen bonds. The number of salt bridges is lowest in HH8-HEL
      and highest in HH26-HEL. The binding site salt bridges in HH8-HEL are not
      networked, and are weak, whereas, in HH26-HEL, an intramolecular salt-bridge
      triad at the binding site is networked to an intermolecular triad to form a
      pentad. The pentad and each salt bridge of this pentad are exceptionally
      stabilizing. The number of binding-site salt bridges and their strengths are
      intermediate in HH10-HEL, with an intramolecular triad. Our further calculations
      show that the electrostatic component contributes the most to binding energy of
      HH26-HEL, whereas the hydrophobic component contributes the most in the case of
      HH8-HEL. A "hot-spot" epitope residue Lys-97 forms an intermolecular salt bridge
      in HH8-HEL, and participates in the intermolecular pentad in the HH26-HEL
      complex. Mutant modeling and surface plasmon resonance (SPR) studies show that
      this hot-spot epitope residue contributes significantly more to the binding than
      an adjacent epitope residue, Lys-96, which does not form a salt bridge in any of
      the three HH-HEL complexes. Furthermore, the effect of mutating Lys-97 is most
      severe in HH26-HEL. Lys-96, being a charged residue, also contributes the most in
      HH26-HEL among the three complexes. The SPR results on these mutants also
      highlight that the apparent "electrostatic steering" on net on rates actually act
      at post-collision level stabilization of the complex. The significance of this
      work is the observed variations in electrostatic interactions among the three
      complexes. Our work demonstrates that higher electrostatics, both as a number of
      short-range electrostatic interactions and their contributions, leads to higher
      binding specificity. Strong salt bridges, their networking, and electrostatically
      driven binding, limit flexibilities through geometric constrains. In contrast,
      hydrophobic driven binding and low levels of electrostatic interactions are
      associated with conformational flexibility and cross-reactivity.

PMID- 12496071
TI  - Residual charge interactions in unfolded staphylococcal nuclease can be explained
      by the Gaussian-chain model.
AB  - The discrepancy of the pH dependence of the unfolding free energy for
      staphylococcal nuclease from what is expected from an idealized model for the
      unfolded state is accounted for by the recently developed Gaussian-chain model.
      Residual electrostatic effects in the unfolded state are attributed to
      nonspecific interactions dominated by charges close along the sequence. The
      dominance of nonspecific local interactions appears to be supported by some
      experimental evidence.

PMID- 12496072
TI  - Gauging of the PhoE channel by a single freely diffusing proton.
AB  - In the present study we combined a continuum approximation with a detailed
      mapping of the electrostatic potential inside an ionic channel to define the most
      probable trajectory for proton propagation through the channel (propagation along
      a structure-supported trajectory (PSST)). The conversion of the three-dimensional
      diffusion space into propagation along a one-dimensional pathway permits
      reconstruction of an ion motion by a short calculation (a few seconds on a state
      of-the-art workstation) rather than a laborious, time-consuming random walk
      simulations. The experimental system selected for testing the accuracy of this
      concept was the reversible dissociation of a proton from a single pyranine
      molecule (8-hydroxypyrene-1,2,3-trisulfonate) bound by electrostatic forces
      inside the PhoE ionic channel of the Escherichia coli outer membrane. The crystal
      structure coordinates were used for calculation of the intra-cavity electrostatic
      potential, and the reconstruction of the observed fluorescence decay curve was
      carried out using the dielectric constant of the intra-cavity space as an
      adjustable parameter. The fitting of past experimental observations (Shimoni, E.,
      Y. Tsfadia, E. Nachliel, and M. Gutman. 1993. Biophys. J. 64:472-479) was carried
      out by a modified version of the Agmon geminate recombination program (Krissinel,
      E. B., and N. Agmon. 1996. J. Comp. Chem. 17:1085-1098), where the gradient of
      the electrostatic potential and the entropic terms were calculated by the PSST
      program. The best-fitted reconstruction of the observed dynamics was attained
      when the water in the cavity was assigned epsilon </= 55, corroborating the
      theoretical estimation of Sansom (Breed, J. R., I. D. Kerr, and M. S. P. Sansom.
      1996. Biophys. J. 70:1643-1661). The dielectric constant calculated for reversed
      micelles of comparable size (Cohen, B., D. Huppert, K. M. Solntsev, Y. Tsfadia,
      E. Nachliel, and M. Gutman. 2002. JACS. 124:7539-7547) allows us to set a margin
      of epsilon = 50 +/- 5.

PMID- 12496073
TI  - A fast in silico simulation of ion flux through the large-pore channel proteins.
AB  - The PSST program (see accompanying article) utilizes the detailed structure of a
      large-pore channel protein as the sole input for selection of trajectories along
      which negative and positive ions propagate. In the present study we applied this
      program to reconstruct the ion flux through five large-pore channel proteins
      (PhoE, OmpF, the WT R. blastica general diffusion porin and two of its mutants).
      The conducting trajectories, one for positive and one for negative particles, are
      contorted pathways that run close to arrays of charged residues on the inner
      surface of the channel. In silico propagation of the charged particles yielded
      passage time values that are compatible with the measured average passage time of
      ions. The calculated ionic mobilities are close to those of the electrolyte
      solution of comparable concentrations. Inspection of the transition probabilities
      along the channel revealed no region that could impose a rate-limiting step. It
      is concluded that the ion flux is a function of the whole array of local
      barriers. Thus, the conductance of the large-pore channel protein is determined
      by the channel's shape and charge distribution, while the selectivity also
      reflects the features of the channel's vestibule.

PMID- 12496075
TI  - Validity of Go models: comparison with a solvent-shielded empirical energy
      decomposition.
AB  - Do Go-type model potentials provide a valid approach for studying protein
      folding? They have been widely used for this purpose because of their simplicity
      and the speed of simulations based on their use. The essential assumption in such
      models is that only contact interactions existing in the native state determine
      the energy surface of a polypeptide chain, even for non-native configurations
      sampled along folding trajectories. Here we use an all-atom molecular mechanics
      energy function to investigate the adequacy of Go-type potentials. We show that,
      although the contact approximation is accurate, non-native contributions to the
      energy can be significant. The assumed relation between residue-residue
      interaction energies and the number of contacts between them is found to be only
      approximate. By contrast, individual residue energies correlate very well with
      the number of contacts. The results demonstrate that models based on the latter
      should give meaningful results (e.g., as used to interpret phi values), whereas
      those that depend on the former are only qualitative, at best.

PMID- 12496074
TI  - Structure modeling of the chemokine receptor CCR5: implications for ligand
      binding and selectivity.
AB  - The G-protein coupled receptor CCR5 is the main co-receptor for macrophage-tropic
      HIV-1 strains. I have built a structural model of the chemokine receptor CCR5 and
      used it to explain the binding and selectivity of the antagonist TAK779. Models
      of the extracellular (EC) domains of CCR5 have been constructed and used to
      rationalize current biological data on the binding of HIV-1 and chemokines.
      Residues spanning the transmembrane region of CCR5 have been modeled after
      rhodopsin, and their functional significance examined using the evolutionary
      trace method. The receptor cavity shares six residues with CC-chemokine receptors
      CCR1 through CCR4, while seven residues are unique to CCR5. The contribution of
      these residues to ligand binding and selectivity is tested by molecular docking
      simulations of TAK779 to CCR1, CCR2, and CCR5. TAK779 binds to CCR5 in the cavity
      formed by helices 1, 2, 3, and 7 with additional interactions with helices 5 and
      6. TAK779 did not dock to either CCR1 or CCR2. The results are consistent with
      current site-directed mutagenesis data and with the observed selectivity of
      TAK779 for CCR5 over CCR1 and CCR2. The specific residues responsible for the
      observed selectivity are identified. The four EC regions of CCR5 have been
      modeled using constrained simulated annealing simulations. Applied dihedral angle
      constraints are representative of the secondary structure propensities of these
      regions. Tertiary interactions, in the form of distance constraints, are
      generated from available epitope mapping data. Analysis of the 250 simulated
      structures provides new insights to the design of experiments aimed at
      determining residue-residue contacts across the EC domains and for mapping CC
      chemokines on the surface of the EC domains.

PMID- 12496076
TI  - Brownian dynamics simulation of rigid particles of arbitrary shape in external
      fields.
AB  - We have developed a Brownian dynamics simulation algorithm to generate Brownian
      trajectories of an isolated, rigid particle of arbitrary shape in the presence of
      electric fields or any other external agents. Starting from the generalized
      diffusion tensor, which can be calculated with the existing HYDRO software, the
      new program BROWNRIG (including a case-specific subprogram for the external
      agent) carries out a simulation that is analyzed later to extract the observable
      dynamic properties. We provide a variety of examples of utilization of this
      method, which serve as tests of its performance, and also illustrate its
      applicability. Examples include free diffusion, transport in an electric field,
      and diffusion in a restricting environment.

PMID- 12496077
TI  - Molecular dynamics study of Desulfovibrio africanus cytochrome c3 in oxidized and
      reduced forms.
AB  - A 5-ns molecular dynamics study of a tetraheme cytochrome in fully oxidized and
      reduced forms was performed using the CHARMM molecular modeling program, with
      explicit water molecules, Langevin dynamics thermalization, Particle Mesh Ewald
      long-range electrostatics, and quantum mechanical determination of heme partial
      charges. The simulations used, as starting points, crystallographic structures of
      the oxidized and reduced forms of the acidic cytochrome c(3) from Desulfovibrio
      africanus obtained at pH 5.6. In this paper we also report structures for the two
      forms obtained at pH 8. In contrast to previous cytochrome c(3) dynamics
      simulations, our model is stable. The simulation structures agree reasonably well
      with the crystallographic ones, but our models show higher flexibility and the
      water molecules are more labile. We have compared in detail the differences
      between the simulated and experimental structures of the two redox states and
      observe that the hydration structure is highly dependent on the redox state. We
      have also analyzed the interaction energy terms between the hemes, the protein
      residues, and water. The direct electrostatic interaction between hemes is weak
      and nearly insensitive to the redox state, but the remaining terms are large and
      contribute in a complex way to the overall potential energy differences that we
      see between the redox states.

PMID- 12496079
TI  - The nuclear pore complex mystery and anomalous diffusion in reversible gels.
AB  - The exchange of macromolecules between the cytoplasm and the nucleus of
      eukaryotic cells takes place through the nuclear pore complex (NPC), which
      contains a selective permeability barrier. Experiments on the physical properties
      of this barrier appear to be in conflict with current physical understanding of
      the rheology of reversible gels. This paper proposes that the NPC gel is
      anomalous and characterized by connectivity fluctuations. It develops a
      simplified model to demonstrate the possibility of enhanced diffusion constants
      of macromolecules trapped in such a gel.

PMID- 12496078
TI  - Driving forces of protein association: the dimer-octamer equilibrium in
      arylsulfatase A.
AB  - The enzyme arylsulfatase A (ASA) occurs in solution as dimer (alpha(2)) above pH
      6 and associates to octamers (alpha(2))(4) below pH 6. The crystal structure of
      ASA suggests that the (alpha(2))-(alpha(2))(4) equilibrium is regulated by
      protonation/deprotonation of Glu-424 located at the interface between (alpha(2))
      dimers in the octamer. The reason for this assumption is that Glu-424 can be in
      two different conformers where it forms an intra or intermolecular hydrogen bond,
      respectively. In the present study we investigate this protein association
      process theoretically. The electrostatic energies are evaluated by solving the
      Poisson-Boltzmann equation for the inhomogeneous dielectric of the protein-water
      system for the dimer and octamer configurations. If a conventional surface energy
      term is used for the nonelectrostatic interactions, the absolute value of free
      energy of association fails to agree with experiment. A more detailed treatment
      that explicitly accounts for hydrophilic and hydrophobic character of the amino
      acids in the dimer-dimer interface of the octamer can explain this discrepancy
      qualitatively. The pH dependence of the computed association energy clearly
      demonstrates that the octamer is more stable at low pH if Glu-424 becomes
      protonated and forms an intermolecular hydrogen bond. We found a slight
      preference of Glu-424 to be in a conformation where its acidic group is fully
      solvent-exposed in the dimer state to form hydrogen bonds with water molecules.
      Application of the proton linkage model to calculate the association energy from
      the simulated data yielded results identical to the one obtained from the
      corresponding direct method.

PMID- 12496080
TI  - Conformational partitioning of the fusion peptide of HIV-1 gp41 and its
      structural analogs in bilayer membranes.
AB  - Experiments have shown that the ability of the HIV-1 virus to infect cells can be
      greatly diminished by deactivation of the N-terminal (fusion) peptide of its
      glycoprotein gp41. Deactivation can be achieved by the deletion of several amino
      acid residues, or replacement of a hydrophobic residue with a polar residue, to
      form mutant variants of the wild-type peptide. We report Monte Carlo simulation
      studies of a simplified peptide/membrane model, representing the interaction of
      an HIV-1 fusion peptide (FP) and four closely related mutagens with a lipid
      bilayer. In agreement with experimental results, we show that FP inserts deeply
      into the bilayer at approximately 40 degrees to the bilayer normal. We also show
      a previously unreported behavior of membrane peptides, namely their equilibrium
      partitioning between several distinct conformations within the bilayer. We
      quantify this partitioning behavior and characterize each conformation in terms
      of its geometry, energy, and entropy. The diminished ability of FP mutagens to
      hemolyse and aggregate red blood cells due to their partitioning into unfavorable
      conformations, is also discussed. Our analysis supports a negative curvature
      mechanism for red blood cell hemolysis by FP. We also suggest that the small
      repulsive forces between surface-adsorbed peptides in opposing membrane surfaces
      may block aggregation.

PMID- 12496081
TI  - Molecular dynamics investigation of primary photoinduced events in the activation
      of rhodopsin.
AB  - Retinal cis-trans isomerization and early relaxation steps have been studied in a
      10-ns molecular dynamics simulation of a fully hydrated model of membrane
      embedded rhodopsin. The isomerization, induced by transiently switching the
      potential energy function governing the C(11)==C(12) dihedral angle of retinal,
      completes within 150 fs and yields a strongly distorted retinal. The most
      significant conformational changes in the binding pocket are straightening of
      retinal's polyene chain and separation of its beta-ionone ring from Trp-265. In
      the following 500 ps, transition of 6s-cis to 6s-trans retinal and dramatic
      changes in the hydrogen bonding network of the binding pocket involving the
      counterion for the protonated Schiff base, Glu-113, occur. Furthermore, the
      energy initially stored internally in the distorted retinal is transformed into
      nonbonding interactions of retinal with its environment. During the following 10
      ns, increased mobilities of some parts of the protein, such as the kinked regions
      of the helices, mainly helix VI, and the intracellular loop I2, were observed, as
      well as transient structural changes involving the conserved salt bridge between
      Glu-134 and Arg-135. These features prepare the protein for major structural
      transformations achieved later in the photocycle. Retinal's motion, in
      particular, can be compared to an opening turnstile freeing the way for the
      proposed rotation of helix VI. This was demonstrated by a steered molecular
      dynamics simulation in which an applied torque enforced the rotation of helix VI.

PMID- 12496082
TI  - Addition of missing loops and domains to protein models by x-ray solution
      scattering.
AB  - Inherent flexibility and conformational heterogeneity in proteins can often
      result in the absence of loops and even entire domains in structures determined
      by x-ray crystallographic or NMR methods. X-ray solution scattering offers the
      possibility of obtaining complementary information regarding the structures of
      these disordered protein regions. Methods are presented for adding missing loops
      or domains by fixing a known structure and building the unknown regions to fit
      the experimental scattering data obtained from the entire particle. Simulated
      annealing was used to minimize a scoring function containing the discrepancy
      between the experimental and calculated patterns and the relevant penalty terms.
      In low-resolution models where interface location between known and unknown parts
      is not available, a gas of dummy residues represents the missing domain. In high
      resolution models where the interface is known, loops or domains are represented
      as interconnected chains (or ensembles of residues with spring forces between the
      C(alpha) atoms), attached to known position(s) in the available structure. Native
      like folds of missing fragments can be obtained by imposing residue-specific
      constraints. After validation in simulated examples, the methods have been
      applied to add missing loops or domains to several proteins where partial
      structures were available.

PMID- 12496083
TI  - Toward the physical basis of thermophilic proteins: linking of enriched polar
      interactions and reduced heat capacity of unfolding.
AB  - The enrichment of salt bridges and hydrogen bonding in thermophilic proteins has
      long been recognized. Another tendency, featuring lower heat capacity of
      unfolding (DeltaC(p)) than found in mesophilic proteins, is emerging from the
      recent literature. Here we present a simple electrostatic model to illustrate
      that formation of a salt-bridge or hydrogen-bonding network around an ionized
      group in the folded state leads to increased folding stability and decreased
      DeltaC(p). We thus suggest that the reduced DeltaC(p) of thermophilic proteins
      could partly be attributed to enriched polar interactions. A reduced DeltaC(p)
      might serve as an indicator for the contribution of polar interactions to folding
      stability.

PMID- 12496084
TI  - Spatiotemporal features of Ca2+ buffering and diffusion in atrial cardiac
      myocytes with inhibited sarcoplasmic reticulum.
AB  - Ca(2+) signaling in cells is largely governed by Ca(2+) diffusion and Ca(2+)
      binding to mobile and stationary Ca(2+) buffers, including organelles. To examine
      Ca(2+) signaling in cardiac atrial myocytes, a mathematical model of Ca(2+)
      diffusion was developed which represents several subcellular compartments,
      including a subsarcolemmal space with restricted diffusion, a myofilament space,
      and the cytosol. The model was used to quantitatively simulate experimental
      Ca(2+) signals in terms of amplitude, time course, and spatial features. For
      experimental reference data, L-type Ca(2+) currents were recorded from atrial
      cells with the whole-cell voltage-clamp technique. Ca(2+) signals were
      simultaneously imaged with the fluorescent Ca(2+) indicator Fluo-3 and a laser
      scanning confocal microscope. The simulations indicate that in atrial myocytes
      lacking T-tubules, Ca(2+) movement from the cell membrane to the center of the
      cells relies strongly on the presence of mobile Ca(2+) buffers, particularly when
      the sarcoplasmic reticulum is inhibited pharmacologically. Furthermore, during
      the influx of Ca(2+) large and steep concentration gradients are predicted
      between the cytosol and the submicroscopically narrow subsarcolemmal space. In
      addition, the computations revealed that, despite its low Ca(2+) affinity, ATP
      acts as a significant buffer and carrier for Ca(2+), even at the modest
      elevations of [Ca(2+)](i) reached during influx of Ca(2+).

PMID- 12496085
TI  - The motion of a single molecule, the lambda-receptor, in the bacterial outer
      membrane.
AB  - Using optical tweezers and single particle tracking, we have revealed the motion
      of a single protein, the lambda-receptor, in the outer membrane of living
      Escherichia coli bacteria. We genetically modified the lambda-receptor placing a
      biotin on an extracellular site of the receptor in vivo. The efficiency of this
      in vivo biotinylation is very low, thus enabling the attachment of a streptavidin
      coated bead binding specifically to a single biotinylated lambda-receptor. The
      bead was used as a handle for the optical tweezers and as a marker for the single
      particle tracking routine. We propose a model that allows extraction of the
      motion of the protein from measurements of the mobility of the bead-molecule
      complex; these results are equally applicable to analyze bead-protein complexes
      in other membrane systems. Within a domain of radius approximately 25 nm, the
      receptor diffuses with a diffusion constant of (1.5 +/- 1.0) x 10(-9) cm(2)/s and
      sits in a harmonic potential as if it were tethered by an elastic spring of
      spring constant of ~1.0 x 10(-2) pN/nm to the bacterial membrane. The purpose of
      the protein motion might be to facilitate transport of maltodextrins through the
      outer bacterial membrane.

PMID- 12496086
TI  - Micromechanical mapping of live cells by multiple-particle-tracking
      microrheology.
AB  - This paper introduces the method of live-cell multiple-particle-tracking
      microrheology (MPTM), which quantifies the local mechanical properties of living
      cells by monitoring the Brownian motion of individual microinjected fluorescent
      particles. Particle tracking of carboxylated microspheres imbedded in the
      cytoplasm produce spatial distributions of cytoplasmic compliances and frequency
      dependent viscoelastic moduli. Swiss 3T3 fibroblasts are found to behave like a
      stiff elastic material when subjected to high rates of deformations and like a
      soft liquid at low rates of deformations. By analyzing the relative contributions
      of the subcellular compliances to the mean compliance, we find that the cytoplasm
      is much more mechanically heterogeneous than reconstituted actin filament
      networks. Carboxylated microspheres embedded in cytoplasm through endocytosis and
      amine-modified polystyrene microspheres, which are microinjected or endocytosed,
      often show directed motion and strong nonspecific interactions with cytoplasmic
      proteins, which prevents computation of local moduli from the microsphere
      displacements. Using MPTM, we investigate the mechanical function of alpha
      actinin in non-muscle cells: alpha-actinin-microinjected cells are stiffer and
      yet mechanically more heterogeneous than control cells, in agreement with models
      of reconstituted cross-linked actin filament networks. MPTM is a new type of
      functional microscopy that can test the local, rate-dependent mechanical and
      ultrastructural properties of living cells.

PMID- 12496087
TI  - Cellular characterization of adenylate kinase and its isoform: two-photon
      excitation fluorescence imaging and fluorescence correlation spectroscopy.
AB  - Adenylate kinase (AK) is a ubiquitous enzyme that regulates the homeostasis of
      adenine nucleotides in the cell. AK1beta (long form) from murine cells shares the
      same protein sequence as AK1 (short form) except for the addition of 18 amino
      acid residues at its N-terminus. It is hypothesized that these residues serve as
      a signal for protein lipid modification and targeting of the protein to the
      plasma membrane. To better understand the cellular function of these AK isoforms,
      we have used several modern fluorescence techniques to characterize these two
      isoforms of AK enzyme. We fused cytosolic adenylate kinase (AK1) and its isoform
      (AK1beta) with enhanced green fluorescence protein (EGFP) and expressed the
      chimera proteins in HeLa cells. Using two-photon excitation scanning fluorescence
      imaging, we were able to directly visualize the localization of AK1-EGFP and
      AK1beta-EGFP in live cells. AK1beta-EGFP mainly localized on the plasma membrane,
      whereas AK1-EGFP distributed throughout the cell except for trace amounts in the
      nuclear membrane and some vesicles. We performed fluorescence correlation
      spectroscopy measurements and photon-counting histogram analysis in specific
      domains of live cells. For AK1-EGFP, we observed only one diffusion component in
      the cytoplasm. For AK1beta-EGFP, we observed two distinct diffusion components on
      the plasma membrane. One corresponded to the free diffusing protein, whereas the
      other represented the membrane-bound AK1beta-EGFP. The diffusion rate of AK1-EGFP
      was slowed by a factor of 1.8 with respect to that of EGFP, which was 50% more
      than what we would expect for a free diffusing AK1-EGFP. To rule out the
      possibility of oligomer formation, we performed photon-counting histogram
      analysis to direct analyze the brightness difference between AK1-EGFP and EGFP.
      From our analysis, we concluded that cytoplasmic AK1-EGFP is monomeric.
      fluorescence correlation spectroscopy proved to be a powerful technique for
      quantitatively studying the mobility of the target protein in live cells. This
      technology offers advantages in studying protein interactions and function in the
      cell.

PMID- 12496088
TI  - Characterization of adaptation motors in saccular hair cells by fluctuation
      analysis.
AB  - The mechanical sensitivity of hair cells, the sensory receptors of the vestibular
      and auditory systems, is maintained by adaptation, which resets the transducer to
      cancel the effects of static stimuli. Adaptation motors in hair cells can be
      experimentally activated by externally applying a transduction channel blocker to
      the hair bundle, causing the hair bundle to move in the negative direction. We
      studied the variance in the position of the hair bundle during these
      displacements and found that it increases as the bundle moves to its new
      position. Often the variance peaks, and then declines to a steady-state value. We
      describe both displacement and variance with a model in which a motor acting on
      the bundle takes approximately 3.6-nm steps whose frequency (approximately 22 s(
      1)) declines with the motor's load.

PMID- 12496089
TI  - Probing distance and electrical potential within a protein pore with tethered
      DNA.
AB  - DNA molecules tethered inside a protein pore can be used as a tool to probe
      distance and electrical potential. The approach and its limitations were tested
      with alpha-hemolysin, a pore of known structure. A single oligonucleotide was
      attached to an engineered cysteine to allow the binding of complementary DNA
      strands inside the wide internal cavity of the extramembranous domain of the
      pore. The reversible binding of individual oligonucleotides produced transient
      current blockades in single channel current recordings. To probe the internal
      structure of the pore, oligonucleotides with 5' overhangs of deoxyadenosines and
      deoxythymidines up to nine bases in length were used. The characteristics of the
      blockades produced by the oligonucleotides indicated that single-stranded
      overhangs of increasing length first approach and then thread into the
      transmembrane beta-barrel. The distance from the point at which the DNA was
      attached and the internal entrance to the barrel is 43 A, consistent with the
      lengths of the DNA probes and the signals produced by them. In addition, the
      tethered DNAs were used to probe the electrical potential within the protein
      pore. Binding events of oligonucleotides with an overhang of five bases or more,
      which threaded into the beta-barrel, exhibited shorter residence times at higher
      applied potentials. This finding is consistent with the idea that the main
      potential drop is across the alpha-hemolysin transmembrane beta-barrel, rather
      than the entire length of the lumen of the pore. It therefore explains why the
      kinetics and thermodynamics of formation of short duplexes within the
      extramembranous cavity of the pore are similar to those measured in solution, and
      bolsters the idea that a "DNA nanopore" provides a useful means for examining
      duplex formation at the single molecule level.

PMID- 12496090
TI  - Modulation of endothelial inward-rectifier K+ current by optical isomers of
      cholesterol.
AB  - Membrane potential of aortic endothelial cells under resting conditions is
      dominated by inward-rectifier K(+) channels belonging to the Kir 2 family.
      Regulation of endothelial Kir by membrane cholesterol was studied in bovine
      aortic endothelial cells by altering the sterol composition of the cell membrane.
      Our results show that enriching the cells with cholesterol decreases the Kir
      current density, whereas depleting the cells of cholesterol increases the density
      of the current. The dependence of the Kir current density on the level of
      cellular cholesterol fits a sigmoid curve with the highest sensitivity of the Kir
      current at normal physiological levels of cholesterol. To investigate the
      mechanism of Kir regulation by cholesterol, endogenous cholesterol was
      substituted by its optical isomer, epicholesterol. Substitution of approximately
      50% of cholesterol by epicholesterol results in an early and significant increase
      in the Kir current density. Furthermore, substitution of cholesterol by
      epicholesterol has a stronger facilitative effect on the current than cholesterol
      depletion. Neither single channel properties nor membrane capacitance were
      significantly affected by the changes in the membrane sterol composition. These
      results suggest that 1) cholesterol modulates cellular K(+) conductance by
      changing the number of the active channels and 2) that specific cholesterol
      protein interactions are critical for the regulation of endothelial Kir.

PMID- 12496091
TI  - The synaptic vesicle protein synaptophysin: purification and characterization of
      its channel activity.
AB  - The synaptic vesicle protein synaptophysin was solubilized from rat brain
      synaptosomes with a relatively low concentration of Triton X-100 (0.2%) and was
      highly purified (above 95%) using a rapid single chromatography step on
      hydroxyapatite/celite resin. Purified synaptophysin was reconstituted into a
      planar lipid bilayer and the channel activity of synaptophysin was characterized.
      In asymmetric KCl solutions (cis 300 mM/trans 100 mM), synaptophysin formed a
      fast-fluctuating channel with a conductance of 414 +/- 13 pS at +60 mV. The open
      probability of synaptophysin channels was decreased upon depolarization, and
      channels were found to be cation-selective. Synaptophysin channels showed higher
      selectivity for K(+) over Cl(-) (P(K(+))/P(Cl(-)) > 8) and preferred K(+) over
      Li(+), Na(+), Rb(+), Cs(+), or choline(+). The synaptophysin channel is
      impermeable to Ca(2+), which has no effect on its channel activity. This study is
      the second demonstration of purified synaptophysin channel activity, but the
      first biophysical characterization of its channel properties. The availability of
      large amounts of purified synaptophysin and of its characteristic channel
      properties might help to establish the role of synaptophysin in synaptic
      transmission.

PMID- 12496092
TI  - Multiple regions of RyR1 mediate functional and structural interactions with
      alpha(1S)-dihydropyridine receptors in skeletal muscle.
AB  - Excitation-contraction (e-c) coupling in muscle relies on the interaction between
      dihydropyridine receptors (DHPRs) and RyRs within Ca(2+) release units (CRUs). In
      skeletal muscle this interaction is bidirectional: alpha(1S)DHPRs trigger RyR1
      (the skeletal form of the ryanodine receptor) to release Ca(2+) in the absence of
      Ca(2+) permeation through the DHPR, and RyR1s, in turn, affect the open
      probability of alpha(1S)DHPRs. alpha(1S)DHPR and RyR1 are linked to each other,
      organizing alpha(1S)-DHPRs into groups of four, or tetrads. In cardiac muscle,
      however, alpha(1C)DHPR Ca(2+) current is important for activation of RyR2 (the
      cardiac isoform of the ryanodine receptor) and alpha(1C)-DHPRs are not organized
      into tetrads. We expressed RyR1, RyR2, and four different RyR1/RyR2 chimeras (R4:
      Sk1635-3720, R9: Sk2659-3720, R10: Sk1635-2559, R16: Sk1837-2154) in 1B5 dyspedic
      myotubes to test their ability to restore skeletal-type e-c coupling and DHPR
      tetrads. The rank-order for restoring skeletal e-c coupling, indicated by Ca(2+)
      transients in the absence of extracellular Ca(2+), is RyR1 > R4 > R10 >> R16 > R9
      >> RyR2. The rank-order for restoration of DHPR tetrads is RyR1 > R4 = R9 > R10 =
      R16 >> RyR2. Because the skeletal segment in R9 does not overlap with that in
      either R10 or R16, our results indicate that multiple regions of RyR1 may
      interact with alpha(1S)DHPRs and that the regions responsible for tetrad
      formation do not correspond exactly to the ones required for functional coupling.

PMID- 12496093
TI  - Ion channel behavior of amphotericin B in sterol-free and cholesterol- or
      ergosterol-containing supported phosphatidylcholine bilayer model membranes
      investigated by electrochemistry and spectroscopy.
AB  - Amphotericin B (AmB) is a popular drug frequently applied in the treatment of
      systemic fungal infections. In the presence of ruthenium (II) as the maker ion,
      the behavior of AmB to form ion channels in sterol-free and cholesterol- or
      ergosterol-containing supported phosphatidylcholine bilayer model membranes were
      studied by cyclic votammetry, AC impedance spectroscopy, and UV/visible
      absorbance spectroscopy. Different concentrations of AmB ranging from a
      molecularly dispersed to a highly aggregated state of the drug were investigated.
      In a fixed cholesterol or ergosterol content (5 mol %) in glassy carbon electrode
      supported model membranes, our results showed that no matter what form of AmB,
      monomeric or aggregated, AmB could form ion channels in supported ergosterol
      containing phosphatidylcholine bilayer model membranes. However, AmB could not
      form ion channels in its monomeric form in sterol-free and cholesterol-containing
      supported model membranes. On the one hand, when AmB is present as an aggregated
      state, it can form ion channels in cholesterol-containing supported model
      membranes; on the other hand, only when AmB is present as a relatively highly
      aggregated state can it form ion channels in sterol-free supported
      phosphatidylcholine bilayer model membranes. The results showed that the state of
      AmB played an important role in forming ion channels in sterol-free and
      cholesterol-containing supported phosphatidylcholine bilayer model membranes.

PMID- 12496094
TI  - Reconstituted slow muscarinic inhibition of neuronal (Ca(v)1.2c) L-type Ca2+
      channels.
AB  - Ca(2+) influx through L-type channels is critical for numerous physiological
      functions. Relatively little is known about modulation of neuronal L-type Ca(2+)
      channels. We studied modulation of neuronal Ca(V)1.2c channels heterologously
      expressed in HEK293 cells with each of the known muscarinic acetylcholine
      receptor subtypes. Galphaq/11-coupled M1, M3, and M5 receptors each produced
      robust inhibition of Ca(V)1.2c, whereas Galphai/o-coupled M2 and M4 receptors
      were ineffective. Channel inhibition through M1 receptors was studied in detail
      and was found to be kinetically slow, voltage-independent, and pertussis toxin
      insensitive. Slow inhibition of Ca(V)1.2c was blocked by coexpressing RGS2 or
      RGS3T or by intracellular dialysis with antibodies directed against Galphaq/11.
      In contrast, inhibition was not reduced by coexpressing betaARK1ct or Galphat.
      These results indicate that slow inhibition required signaling by Galphaq/11, but
      not Gbetagamma, subunits. Slow inhibition did not require Ca(2+) transients or
      Ca(2+) influx through Ca(V)1.2c channels. Additionally, slow inhibition was
      insensitive to pharmacological inhibitors of phospholipases, protein kinases, and
      protein phosphatases. Intracellular BAPTA prevented slow inhibition via a
      mechanism other than Ca(2+) chelation. The cardiac splice-variant of Ca(V)1.2
      (Ca(V)1.2a) and a splice-variant of the neuronal/neuroendocrine Ca(V)1.3 channel
      also appeared to undergo slow muscarinic inhibition. Thus, slow muscarinic
      inhibition may be a general characteristic of L-type channels having widespread
      physiological significance.

PMID- 12496095
TI  - Flux coupling in the human serotonin transporter.
AB  - The serotonin (5-hydroxytryptamine; 5HT) transporter (SERT) catalyzes the
      movement of 5HT across cellular membranes. In the brain, SERT clears 5HT from
      extracellular spaces, modulating the strength and duration of serotonergic
      signaling. SERT is also an important pharmacological target for antidepressants
      and drugs of abuse. We have studied the flux of radio-labeled 5HT through the
      transporter stably expressed in HEK-293 cells. Analysis of the time course of net
      transport, the equilibrium 5HT gradient sustained, and the ratio of the
      unidirectional influx to efflux of 5HT indicate that mechanistically, human SERT
      functions as a 5HT channel rather than a classical carrier. This is especially
      apparent at relatively high [5HT](out) (> or =10 microM), but is not restricted
      to this regime of external 5HT.

PMID- 12496096
TI  - Movement of the C-helix during the gating of cyclic nucleotide-gated channels.
AB  - Movements within the cyclic nucleotide-binding domain of cyclic nucleotide-gated
      channels are thought to underlie the initial phase of channel gating (Tibbs, G.
      R., D. T. Liu, B. G. Leypold, and S. A. Siegelbaum. 1998. J. Biol. Chem. 273:4497
      4505; Zong, X., H. Zucker, F. Hofmann, and M. Biel. 1998. EMBO J. 17:353-362;
      Matulef, K., G. E. Flynn, and W. N. Zagotta. 1999. Neuron. 24:443-452; Paoletti,
      P., E. C. Young, and S. A. Siegelbaum. 1999. J. Gen. Physiol. 113:17-33; Johnson,
      J. P., and W. N. Zagotta. 2001. Nature. 412:917-921). To investigate these
      movements, cysteine mutation was performed on each of the 28 residues (Leu-583 to
      Asn-610), which span the agonist-binding domain of the alpha-subunit of the
      bovine rod cyclic nucleotide-gated channel. The effects of Cd(2+) ions, 2
      trimethylammonioethylmethane thiosulfonate (MTSET) and copper phenanthroline
      (CuP) on channel activity were examined, in excised inside-out patches in the
      presence and in the absence of a saturating concentration of cGMP. The
      application of 100 microM Cd(2+) in the presence of saturating concentration of
      cGMP caused an irreversible and almost complete reduction of the current in
      mutant channels E594C, I600C, and L601C. In the absence of cGMP, the presence of
      100 microM Cd(2+) caused a strong current reduction in all cysteine mutants from
      Asp-588 to Leu-607, with the exception of mutant channels A589C, M592C, M602C,
      K603C, and L606C. The selective effect of Cd(2+) ions was very similar to that
      observed when adding the oxidizing agent CuP to the bath medium, except for
      mutant channel G597C, where CuP caused a stronger current decrease (67 +/- 7%)
      than Cd(2+) (23 +/- 4%). In the absence of cGMP, MTSET caused a reduction of the
      current by >40% in mutant channels L607C, L601C, I600C, G597C, and E594C, whereas
      in the presence of cGMP only mutant channel L601C was affected. The application
      of MTSET protected many mutant channels from the effects of Cd(2+) and CuP. These
      results suggest that, when CNG channels are in the open state, residues from Asp
      588 to Leu-607 are in an alpha-helical structure, homologous to the C-helix of
      the catabolite gene activator protein (Weber, I. T., and T. A. Steitz. 1987. J.
      Mol. Biol. 198:311-326). Furthermore, residues Glu-594, Gly-597, Ile-600, and Leu
      601 of these helices belonging to two different subunits must be in close
      proximity. In the closed state the C-helices are in a different configuration and
      undergo significant fluctuations.

PMID- 12496097
TI  - Ion channels in small cells and subcellular structures can be studied with a
      smart patch-clamp system.
AB  - We have developed a scanning patch-clamp technique that facilitates single
      channel recording from small cells and submicron cellular structures that are
      inaccessible by conventional methods. The scanning patch-clamp technique combines
      scanning ion conductance microscopy and patch-clamp recording through a single
      glass nanopipette probe. In this method the nanopipette is first scanned over a
      cell surface, using current feedback, to obtain a high-resolution topographic
      image. This same pipette is then used to make the patch-clamp recording. Because
      image information is obtained via the patch electrode it can be used to position
      the pipette onto a cell with nanometer precision. The utility of this technique
      is demonstrated by obtaining ion channel recordings from the top of epithelial
      microvilli and openings of cardiomyocyte T-tubules. Furthermore, for the first
      time we have demonstrated that it is possible to record ion channels from very
      small cells, such as sperm cells, under physiological conditions as well as
      record from cellular microstructures such as submicron neuronal processes.

PMID- 12496098
TI  - Staggering of subunits in NMDAR channels.
AB  - Functional N-methyl-D-aspartate receptors (NMDARs) are heteromultimers formed by
      NR1 and NR2 subunits. The M3 segment, as contributed by NR1, forms the core of
      the extracellular vestibule, including binding sites for channel blockers, and
      represents a critical molecular link between ligand binding and channel opening.
      Taking advantage of the substituted cysteine accessibility method along with
      channel block and multivalent coordination, we studied the contribution of the M3
      segment in NR2C to the extracellular vestibule. We find that the M3 segment in
      NR2C, like that in NR1, contributes to the core of the extracellular vestibule.
      However, the M3 segments from the two subunits are staggered relative to each
      other in the vertical axis of the channel. Compared to NR1, homologous positions
      in NR2C, including those in the highly conserved SYTANLAAF motif, are located
      about four amino acids more externally. The staggering of subunits may represent
      a key structural feature underlying the distinct functional properties of NMDARs.

PMID- 12496099
TI  - Transbilayer movement of phospholipids at the main phase transition of lipid
      membranes: implications for rapid flip-flop in biological membranes.
AB  - The transbilayer movement of fluorescent phospholipid analogs in liposomes was
      studied at the lipid phase transition of phospholipid membranes. Two NBD-labeled
      analogs were used, one bearing the fluorescent moiety at a short fatty acid chain
      in the sn-2 position (C(6)-NBD-PC) and one headgroup-labeled analog having two
      long fatty acyl chains (N-NBD-PE). The transbilayer redistribution of the analogs
      was assessed by a dithionite-based assay. We observed a drastic increase of the
      transbilayer movement of both analogs at the lipid phase transition of DPPC (T(c)
      = 41 degrees C) and DMPC (T(c) = 23 degrees C). The flip-flop of analogs was fast
      at the T(c) of DPPC with a half-time (t(1/2)) of ~6-10 min and even faster at the
      T(c) of DMPC with t(1/2) on the order of <2 min, as shown for C(6)-NBD-PC.
      Suppressing the phase transition by the addition of cholesterol, the rapid
      transbilayer movement was abolished. Molecular packing defects at the phase
      transition are assumed to be responsible for the rapid transbilayer movement. The
      relevance of those defects for understanding of the activity of flippases is
      discussed.

PMID- 12496100
TI  - Structure of gel phase DMPC determined by X-ray diffraction.
AB  - The structure of fully hydrated gel phase dimyristoylphosphatidylcholine lipid
      bilayers was obtained at 10 degrees C. Oriented lipid multilayers were used to
      obtain high signal-to-noise intensity data. The chain tilt angle and an estimate
      of the methylene electron density were obtained from wide angle reflections. The
      chain tilt angle is measured to be 32.3 +/- 0.6 degrees near full hydration, and
      it does not change as the sample is mildly dehydrated from a repeat spacing of D
      = 59.9 A to D = 56.5 A. Low angle diffraction peaks were obtained up to the tenth
      order for 17 samples with variable D and prepared by three different methods with
      different geometries. In addition to the usual Fourier reconstructions of the
      electron density profiles, model electron density profiles were fit to all the
      low angle data simultaneously while constraining the model to include the wide
      angle data and the measured lipid volume. Results are obtained for area/lipid (A
      = 47.2 +/- 0.5 A(2)), the compressibility modulus (K(A) = 500 +/- 100 dyn/cm),
      various thicknesses, such as the hydrocarbon thickness (2D(C) = 30.3 +/- 0.2 A),
      and the head-to-head spacing (D(HH) = 40.1 +/- 0.1 A).

PMID- 12496101
TI  - Solid-state 19F-NMR analysis of 19F-labeled tryptophan in gramicidin A in
      oriented membranes.
AB  - The response of membrane-associated peptides toward the lipid environment or
      other binding partners can be monitored by solid-state NMR of suitably labeled
      side chains. Tryptophan is a prominent amino acid in transmembrane helices, and
      its (19)F-labeled analogues are generally biocompatible and cause little
      structural perturbation. Hence, we use 5F-Trp as a highly sensitive NMR probe to
      monitor the conformation and dynamics of the indole ring. To establish this (19)F
      NMR strategy, gramicidin A was labeled with 5F-Trp in position 13 or 15, whose
      chi(1)/chi(2) torsion angles are known from previous (2)H-NMR studies. First, the
      alignment of the (19)F chemical shift anisotropy tensor within the membrane was
      deduced by lineshape analysis of oriented samples. Next, the three principal axes
      of the (19)F chemical shift anisotropy tensor were assigned within the molecular
      frame of the indole ring. Finally, determination of chi(1)/chi(2) for 5F-Trp in
      the lipid gel phase showed that the side chain alignment differs by up to 20
      degrees from its known conformation in the liquid crystalline state. The
      sensitivity gain of (19)F-NMR and the reduction in the amount of material was at
      least 10-fold compared with previous (2)H-NMR studies on the same system and 100
      fold compared with (15)N-NMR.

PMID- 12496102
TI  - Use of a biomimetic chromatographic stationary phase for study of the
      interactions occurring between inorganic anions and phosphatidylcholine
      membranes.
AB  - A liquid chromatographic method for the study of ion-membrane interactions is
      reported. A phosphatidylcholine biomimetic stationary phase was established by
      loading dimyristoylphosphatidylcholine (DMPC) onto a reversed-phase
      octadecylsilica packed column. This column was then used to study the interaction
      of some inorganic anions with the stationary phase by UV and conductivity
      detection. Ten inorganic anions were selected as model ions and were analyzed
      with the proposed chromatographic system. Anion-DMPC interactions of differing
      magnitudes were observed for all of the model anions. Perchlorate-DMPC
      interactions were strongest, followed by thiocyanate-DMPC, iodide-DMPC, chlorate
      DMPC, nitrate-DMPC, bromide-DMPC, chloride-DMPC, fluoride-DMPC, and then sulfate
      DMPC. Cations in the eluent, especially H(+) ions and divalent cations such as
      Ca(2+), showed strong effects on anion-DMPC interactions. The chromatographic
      data suggest that DMPC interacts with both the anions and the cations. Anion-DMPC
      interactions were dependent on the surface potential of the stationary phase: at
      low surface potentials anion-DMPC interactions were predominantly solvation
      dependent in nature whereas at more positive surface potentials anion-DMPC
      interactions were predominantly electrostatic in nature. Cation-DMPC interactions
      served to raise the surface potential, causing the anion-DMPC interactions to
      vary from solvation dependent to electrostatic. The chromatographic data were
      used to provide quantitative estimates of the enthalpies of the anion-DMPC
      interactions.

PMID- 12496103
TI  - Bridging microscopic and mesoscopic simulations of lipid bilayers.
AB  - A lipid bilayer is modeled using a mesoscopic model designed to bridge atomistic
      bilayer simulations with macro-scale continuum-level simulation. Key material
      properties obtained from detailed atomistic-level simulations are used to
      parameterize the meso-scale model. The fundamental length and time scale of the
      meso-scale simulation are at least an order of magnitude beyond that used at the
      atomistic level. Dissipative particle dynamics cast in a new membrane formulation
      provides the simulation methodology. A meso-scale representation of a
      dimyristoylphosphatidylcholine membrane is examined in the high and low surface
      tension regimes. At high surface tensions, the calculated modulus is found to be
      slightly less than the atomistically determined value. This result agrees with
      the theoretical prediction that high-strain thermal undulations still persist,
      which have the effect of reducing the value of the atomistically determined
      modulus. Zero surface tension simulations indicate the presence of strong thermal
      undulatory modes, whereas the undulation spectrum and the calculated bending
      modulus are in excellent agreement with theoretical predictions and experiment.

PMID- 12496104
TI  - Early steps of supported bilayer formation probed by single vesicle fluorescence
      assays.
AB  - We have developed a single vesicle assay to study the mechanisms of supported
      bilayer formation. Fluorescently labeled, unilamellar vesicles (30-100 nm
      diameter) were first adsorbed to a quartz surface at low enough surface
      concentrations to visualize single vesicles. Fusion and rupture events during the
      bilayer formation, induced by the subsequent addition of unlabeled vesicles, were
      detected by measuring two-color fluorescence signals simultaneously. Lipid
      conjugated dyes monitored the membrane fusion while encapsulated dyes reported on
      the vesicle rupture. Four dominant pathways were observed, each exhibiting
      characteristic two-color fluorescence signatures: 1) primary fusion, in which an
      unlabeled vesicle fuses with a labeled vesicle on the surface, is signified by
      the dequenching of the lipid-conjugated dyes followed by rupture and final
      merging into the bilayer; 2) simultaneous fusion and rupture, in which a labeled
      vesicle on the surface ruptures simultaneously upon fusion with an unlabeled
      vesicle; 3) no dequenching, in which loss of fluorescence signal from both dyes
      occur simultaneously with the final merger into the bilayer; and 4) isolated
      rupture (pre-ruptured vesicles), in which a labeled vesicle on the surface
      spontaneously undergoes content loss, a process that occurs with high efficiency
      in the presence of a high concentration of Texas Red-labeled lipids. Vesicles
      that have undergone content loss appear to be more fusogenic than intact
      vesicles.

PMID- 12496105
TI  - Obstructed diffusion in phase-separated supported lipid bilayers: a combined
      atomic force microscopy and fluorescence recovery after photobleaching approach.
AB  - Proteins and other macromolecules are believed to hinder molecular lateral
      diffusion in cellular membranes. We have constructed a well-characterized model
      system to better understand how obstacles in lipid bilayers obstruct diffusion.
      Fluorescence recovery after photobleaching was used to measure the lateral
      diffusion coefficient in single supported bilayers composed of mixtures of 1,2
      dilauroylphosphotidylcholine (DLPC) and 1,2-distearoylphosphotidylcholine (DSPC).
      Because these lipids are immiscible and phase separate at room temperature, a
      novel quenching technique allowed us to construct fluid DLPC bilayers containing
      small disk-shaped gel-phase DSPC domains that acted as obstacles to lateral
      diffusion. Our experimental setup enabled us to analyze the same samples with
      atomic force microscopy and exactly characterize the size, shape, and number of
      gel-phase domains before measuring the obstacle-dependent diffusion coefficient.
      Lateral obstructed diffusion was found to be dependent on obstacle area fraction,
      size, and geometry. Analysis of our results using a free area diffusion model
      shows the possibility of unexpected long-range ordering of fluid-phase lipids
      around the gel-phase obstacles. This lipid ordering has implications for lipid
      mediated protein interactions in cellular membranes.

PMID- 12496106
TI  - Membrane protein crystallization in meso: lipid type-tailoring of the cubic
      phase.
AB  - Hydrated monoolein forms the cubic-Pn3m mesophase that has been used for in meso
      crystallization of membrane proteins. The crystals have subsequently provided
      high-resolution structures by crystallographic means. It is possible that the
      hosting cubic phase created by monoolein alone, which itself is not a common
      membrane component, will limit the range of membrane proteins crystallizable by
      the in meso method. With a view to expanding the range of applicability of the
      method, we investigated by x-ray diffraction the degree to which the reference
      cubic-Pn3m phase formed by hydrated monoolein could be modified by other lipid
      types. These included phosphatidylcholine (PC), phosphatidylethanolamine,
      phosphatidylserine, cardiolipin, lyso-PC, a polyethylene glycol-lipid, 2
      monoolein, oleamide, and cholesterol. The results show that all nine lipids were
      accommodated in the cubic phase to some extent without altering phase identity.
      The positional isomer, 2-monoolein, was tolerated to the highest level. The least
      well tolerated were the anionic lipids, followed by lyso-PC. The others were
      accommodated to the extent of 20-25 mol %. Beyond a certain concentration limit,
      the lipid additives either triggered one or a series of phase transitions or
      saturated the phase and separated out as crystals, as seen with oleamide and
      cholesterol. The series of phases observed and their order of appearance were
      consistent with expectations in terms of interfacial curvature changes. The
      changes in phase type and microstructure have been rationalized on the basis of
      lipid molecular shape, interfacial curvature, and chain packing energy. The data
      should prove useful in the rational design of cubic phase crystallization
      matrices with different lipid profiles that match the needs of a greater range of
      membrane proteins.

PMID- 12496107
TI  - Determination of membrane cholesterol partition coefficient using a lipid vesicle
      cyclodextrin binary system: effect of phospholipid acyl chain unsaturation and
      headgroup composition.
AB  - Lateral domain or raft formation in biological membranes is often discussed in
      terms of cholesterol-lipid interactions. Preferential interactions of cholesterol
      with lipids, varying in headgroup and acyl chain unsaturation, were studied by
      measuring the partition coefficient for cholesterol in unilamellar vesicles. A
      novel vesicle-cyclodextrin system was used, which precludes the possibility of
      cross-contamination between donor-acceptor vesicles or the need to modify one of
      the vesicle populations. Variation in phospholipid headgroup resulted in
      cholesterol partitioning in the order of sphingomyelin (SM) > phosphatidylserine
      > phosphatidylcholine (PC) > phosphatidylenthanolamine (PE), spanning a range of
      partition DeltaG of -1181 cal/mol to +683 cal/mol for SM and PE, respectively.
      Among the acyl chains examined, the order of cholesterol partitioning was
      18:0(stearic acid),18:1n-9(oleic acid) PC > di18:1n-9PC > di18:1n-12(petroselenic
      acid) PC > di18:2n-6(linoleic acid) PC > 16:0(palmitic acid),22:6n-3(DHA) PC >
      di18:3n-3(alpha-linolenic acid) PC > di22:6n-3PC with a range in partition DeltaG
      of 913 cal/mol. Our results suggest that the large differences observed in
      cholesterol-lipid interactions contribute to the forces responsible for lateral
      domain formation in plasma membranes. These differences may also be responsible
      for the heterogeneous cholesterol distribution in cellular membranes, where
      cholesterol is highly enriched in plasma membranes and relatively depleted in
      intracellular membranes.

PMID- 12496108
TI  - Bidirectional control of sphingomyelinase activity and surface topography in
      lipid monolayers.
AB  - Lipid lateral organization is increasingly found to modulate membrane-bound
      enzymes. We followed in real time the reaction course of sphingomyelin (SM)
      degradation by Bacillus cereus sphingomyelinase (SMase) of lipid monolayers by
      epifluorescence microscopy. There is evidence that formation of ceramide (Cer), a
      lipid second messenger, drives structural reorganization of membrane lipids. Our
      results provide visual evidence that SMase activity initially alters surface
      topography by inducing phase separation into condensed (Cer-enriched) and
      expanded (SM-enriched) domains. The Cer-enriched phase grows steadily as the
      reaction proceeds at a constant rate. The surface topography derived from the
      SMase-driven reaction was compared with, and found to differ from, that of
      premixed SM/Cer monolayers of the same lipid composition, indicating that
      substantial information content is stored depending on the manner in which the
      surface was generated. The long-range topographic changes feed back on the
      kinetics of Smase, and the onset of condensed-phase percolation is temporally
      correlated with a rapid drop of reaction rate. These observations reveal a
      bidirectional influence and communication between effects taking place at the
      local molecular level and the supramolecular organization. The results suggest a
      novel biocatalytic-topographic mechanism in which a surface enzymatic activity
      can influence the function of amphitropic proteins important for cell function.

PMID- 12496109
TI  - A simple model with myofilament compliance predicts activation-dependent
      crossbridge kinetics in skinned skeletal fibers.
AB  - The contribution of thick and thin filaments to skeletal muscle fiber compliance
      has been shown to be significant. If similar to the compliance of cycling cross
      bridges, myofilament compliance could explain the difference in time course of
      stiffness and force during the rise of tension in a tetanus as well as the
      difference in Ca(2+) sensitivity of force and stiffness and more rapid phase 2
      tension recovery (r) at low Ca(2+) activation. To characterize the contribution
      of myofilament compliance to sarcomere compliance and isometric force kinetics,
      the Ca(2+)-activation dependence of sarcomere compliance in single glycerinated
      rabbit psoas fibers, in the presence of ATP (5.0 mM), was measured using rapid
      length steps. At steady sarcomere length, the dependence of sarcomere compliance
      on the level of Ca(2+)-activated force was similar in form to that observed for
      fibers in rigor where force was varied by changing length. Additionally, the
      ratio of stiffness/force was elevated at lower force (low [Ca(2+)]) and r was
      faster, compared with maximum activation. A simple series mechanical model of
      myofilament and cross-bridge compliance in which only strong cross-bridge binding
      was activation dependent was used to describe the data. The model fit the data
      and predicted that the observed activation dependence of r can be explained if
      myofilament compliance contributes 60-70% of the total fiber compliance, with no
      requirement that actomyosin kinetics be [Ca(2+)] dependent or that cooperative
      interactions contribute to strong cross-bridge binding.

PMID- 12496110
TI  - Steered molecular dynamics studies of titin I1 domain unfolding.
AB  - The cardiac muscle protein titin, responsible for developing passive elasticity
      and extensibility of muscle, possesses about 40 immunoglobulin-like (Ig) domains
      in its I-band region. Atomic force microscopy (AFM) and steered molecular
      dynamics (SMD) have been successfully combined to investigate the reversible
      unfolding of individual Ig domains. However, previous SMD studies of titin I-band
      modules have been restricted to I27, the only structurally known Ig domain from
      the distal region of the titin I-band. In this paper we report SMD simulations
      unfolding I1, the first structurally available Ig domain from the proximal region
      of the titin I-band. The simulations are carried out with a view toward upcoming
      atomic force microscopy experiments. Both constant velocity and constant force
      stretching have been employed to model mechanical unfolding of oxidized I1, which
      has a disulfide bond bridging beta-strands C and E, as well as reduced I1, in
      which the disulfide bridge is absent. The simulations reveal that I1 is protected
      against external stress mainly through six interstrand hydrogen bonds between its
      A and B beta-strands. The disulfide bond enhances the mechanical stability of
      oxidized I1 domains by restricting the rupture of backbone hydrogen bonds between
      the A'- and G-strands. The disulfide bond also limits the maximum extension of I1
      to approximately 220 A. Comparison of the unfolding pathways of I1 and I27 are
      provided and implications to AFM experiments are discussed.

PMID- 12496111
TI  - Sequence-dependent dynamics of duplex DNA: the applicability of a dinucleotide
      model.
AB  - The short-time (submicrosecond) bending dynamics of duplex DNA were measured to
      determine the effect of sequence on dynamics. All measurements were obtained from
      a single site on duplex DNA, using a single, site-specific modified base
      containing a rigidly tethered, electron paramagnetic resonance active spin probe.
      The observed dynamics are interpreted in terms of single-step sequence-dependent
      bending force constants, determined from the mean squared amplitude of bending
      relative to the end-to-end vector using the modified weakly bending rod model.
      The bending dynamics at a single site are a function of the sequence of the
      nucleotides constituting the duplex DNA. We developed and examined several
      dinucleotide-based models for flexibility. The models indicate that the dominant
      feature of the dynamics is best explained in terms of purine- and pyrimidine-type
      steps, although distinction is made among all 10 unique steps: It was found that
      purine-purine steps (which are the same as pyrimidine-pyrimidine steps) were near
      average in flexibility, but the pyrimidine-purine steps (5' to 3') were nearly
      twice as flexible, whereas purine-pyrimidine steps were more than half as
      flexible as average DNA. Therefore, the range of stepwise flexibility is
      approximately fourfold and is characterized by both the type of base pair step
      (pyrimidine/purine combination) and the identity of the bases within the pair (G,
      A, T, or C). All of the four models considered here underscore the complexity of
      the dependence of dynamics on DNA sequence with certain sequences not
      satisfactorily explainable in terms of any dinucleotide model. These findings
      provide a quantitative basis for interpreting the dynamics and kinetics of DNA
      sequence-dependent biological processes, including protein recognition and
      chromatin packaging.

PMID- 12496112
TI  - Bacteriorhodopsin analog regenerated with 13-desmethyl-13-iodoretinal.
AB  - The retinal analog 13-desmethyl-13-iodoretinal (13-iodoretinal) was newly
      synthesized and incorporated into apomembranes to reconstitute bacteriorhodopsin
      analog 13-I-bR. The absorption maximum was 598 nm and 97% of the chromophore was
      an all-trans isomer in the dark- and light-adapted state. Upon flash
      illumination, 13-I-bR underwent a transient spectral change in which a shorter
      wavelength intermediate (lambda(max) = 426 nm) similar to the M species of the
      native bR developed. Also, 13-I-bR showed light-induced proton pumping with rates
      and extents comparable to those seen in the native bR. The ultraviolet circular
      dichroism (CD) spectrum originating from the aromatic groups was different from
      that of the native bR, indicating that the substituted bulky iodine atom strongly
      interacts with neighboring amino acids. A projection difference Fourier map
      showed the labeled iodine was in the vicinity of helix C. 13-I-bR is an
      advantageous specimen for kinetic investigations of light-induced structural
      changes associated with the proton pumping cycle by x-ray diffraction.

PMID- 12496113
TI  - Equilibrium and kinetic studies of the interactions of a porphyrin with low
      density lipoproteins.
AB  - Low-density lipoproteins (LDL) play a key role in the delivery of
      photosensitizers to tumor cells in photodynamic therapy. The interaction of
      deuteroporphyrin, an amphiphilic porphyrin, with LDL is examined at equilibrium
      and the kinetics of association/dissociation are determined by stopped-flow.
      Changes in apoprotein and porphyrin fluorescence suggest two classes of bound
      porphyrins. The first class, characterized by tryptophan fluorescence quenching,
      involves four well-defined sites. The affinity constant per site is 8.75 x 10(7)
      M(-1) (cumulative affinity 3.5 x 10(8) M(-1)). The second class corresponds to
      the incorporation of up to 50 molecules into the outer lipidic layer of LDL with
      an affinity constant of 2 x 10(8) M(-1). Stopped-flow experiments involving
      direct LDL porphyrin mixing or porphyrin transfer from preloaded LDL to albumin
      provide kinetic characterization of the two classes. The rate constants for
      dissociation of the first and second classes are 5.8 and 15 s(-1); the
      association rate constants are 5 x 10(8) M(-1) s(-1) per site and 3 x 10(9) M(-1)
      s(-1), respectively. Both fluorescence and kinetic analysis indicate that the
      first class involves regions at the boundary between lipids and the apoprotein.
      The kinetics of porphyrin-LDL interactions indicates that changes in the
      distribution of photosensitizers among various carriers could be very sensitive
      to the specific tumor microenvironment.

PMID- 12496114
TI  - FTIR spectroscopy of the M photointermediate in pharaonis rhoborhodopsin.
AB  - pharaonis phoborhodopsin (ppR; also called pharaonis sensory rhodopsin II, psR
      II) is a photoreceptor for negative phototaxis in Natronobacterium pharaonis.
      During the photocycle of ppR, the Schiff base of the retinal chromophore is
      deprotonated upon formation of the M intermediate (ppR(M)). The present FTIR
      spectroscopy of ppR(M) revealed that the Schiff base proton is transferred to Asp
      75, which corresponds to Asp-85 in a light-driven proton-pump bacteriorhodopsin
      (BR). In addition, the C==O stretching vibrations of Asn-105 were assigned for
      ppR and ppR(M). The common hydrogen-bonding alterations in Asn-105 of ppR and Asp
      115 of BR were found in the process from photoisomerization (K intermediate) to
      the primary proton transfer (M intermediate). These results implicate similar
      protein structural changes between ppR and BR. However, BR(M) decays to BR(N)
      accompanying a proton transfer from Asp-96 to the Schiff base and largely changed
      protein structure. In the D96N mutant protein of BR that lacks a proton donor to
      the Schiff base, the N-like protein structure was observed with the deprotonated
      Schiff base (called M(N)) at alkaline pH. In ppR, such an N-like (M(N)-like)
      structure was not observed at alkaline pH, suggesting that the protein structure
      of the M state activates its transducer protein.

PMID- 12496115
TI  - Pressure dependence of the photocycle kinetics of bacteriorhodopsin.
AB  - The pressure dependence of the photocycle kinetics of bacteriorhodopsin from
      Halobacterium salinarium was investigated at pressures up to 4 kbar at 25 degrees
      C and 40 degrees C. The kinetics can be adequately modeled by nine apparent rate
      constants, which are assigned to irreversible transitions of a single relaxation
      chain of nine kinetically distinguishable states P(1) to P(9). All states except
      P(1) and P(9) consist of two or more spectral components. The kinetic states P(2)
      to P(6) comprise only the two fast equilibrating spectral states L and M. From
      the pressure dependence, the volume differences DeltaV(o)(LM) between these two
      spectral states could be determined that range from DeltaV(o)(LM) = -11.4 +/- 0.7
      ml/mol (P(2)) to DeltaV(o)(LM) = 14.6 +/- 2.8 mL/mol (P(6)). A model is developed
      that explains the dependence of DeltaV(o)(LM) on the kinetic state by the
      electrostriction effect of charges, which are formed and neutralized during the
      L/M transition.

PMID- 12496116
TI  - Resonance energy transfer in a calcium concentration-dependent cameleon protein.
AB  - We report investigations of resonance energy transfer in the green fluorescent
      protein and calmodulin-based fluorescent indicator constructs for Ca(2+) called
      cameleons using steady-state and time-resolved spectroscopy of the full construct
      and of the component green fluorescent protein mutants, namely ECFP (donor) and
      EYFP (acceptor). EYFP displays a complicated photophysical behavior including
      protonated and deprotonated species involved in an excited-state proton transfer.
      When EYFP is excited in the absorption band of the protonated species, a fast
      nonradiative deactivation occurs involving almost 97% of the excited protonated
      population and leading to a low efficiency of excited-state proton transfer to
      the deprotonated species. ECFP displays a multiexponential fluorescence decay
      with a major contributing component of 3.2 ns. The time-resolved fluorescence
      data obtained upon excitation at 420 nm of Ca(2+)-free and Ca(2+)-bound YC3.1
      cameleon constructs point to the existence of different conformations of
      calmodulin dependent on Ca(2+) binding. Whereas steady-state data show only an
      increase in the efficiency of energy transfer upon Ca(2+) binding, the time
      resolved data demonstrate the existence of three distinct
      conformations/populations within the investigated sample. Although the mechanism
      of the interconversion between the different conformations and the extent of
      interconversion are still unclear, the time-resolved fluorescence data offer an
      estimation of the rate constants, of the efficiency of the energy transfer, and
      of the donor-acceptor distances in the Ca(2+)-free and Ca(2+)-bound YC3.1
      samples.

PMID- 12496117
TI  - An x-ray absorption spectroscopy study of the zinc environment in Langmuir
      Blodgett phospholipid multilayers.
AB  - For the first time x-ray absorption spectroscopy was used to investigate the Zn
      environment in Langmuir-Blodgett multilayers. The multilayers were taken as a
      model of the multilamellar structure of the myelin sheath, the membrane
      surrounding the nerve axon, which plays a crucial role for signal transduction
      along the axon. The layers were assembled from the phospholipid
      dilauroylphosphatidic acid, both in the presence and in the absence of myelin
      basic protein. The analysis of the extended x-ray absorption fine structure and
      of the near edge regions of the x-ray absorption spectra at the Zn K-edge
      provided an accurate description of the local structure showing that the Zn ions
      are bound to the heads of the phospholipid molecules. The myelin basic protein
      induces a distortion on the Zn local environment due to a steric constraint but
      does not substitute the phosphate headgroups. These findings represent an
      important step in understanding the interplay among myelin basic protein, Zn, and
      the lipids of the myelin sheath.

PMID- 12496118
TI  - Solution studies and structural model of the extracellular domain of the human
      amyloid precursor protein.
AB  - The amyloid precursor protein (APP) is the precursor of the beta-amyloid peptide
      (Abeta), which is centrally related to the genesis of Alzheimer's disease (AD).
      In addition, APP has been suggested to mediate and/or participate in events that
      lead to neuronal degeneration in AD. Despite the fact that various aspects of the
      cell biology of APP have been investigated, little information on the structure
      of this protein is available. In this work, the solution structure of the soluble
      extracellular domain of APP (sAPP, composing 89% of the amino acid residues of
      the whole protein) has been investigated through a combination of size-exclusion
      chromatography, circular dichroism, and synchrotron radiation small-angle x-ray
      scattering (SAXS) studies. sAPP is monomeric in solution (65 kDa obtained from
      SAXS measurements) and exhibits an anisometric molecular shape, with a Stokes
      radius of 39 or 51 A calculated from SAXS or chromatographic data, respectively.
      The radius of gyration and the maximum molecular length obtained by SAXS were 38
      A and 130 A, respectively. Analysis of SAXS data further allowed building a
      structural model for sAPP in solution. Circular dichroism data and secondary
      structure predictions based on the amino acid sequence of APP suggested that a
      significant fraction of APP (30% of the amino acid residues) is not involved in
      standard secondary structure elements, which may explain the elongated shape of
      the molecule recovered in our structural model. Possible implications of the
      structure of APP in ligand binding and molecular recognition events involved in
      the biological functions of this protein are discussed.

PMID- 12496119
TI  - Direct molecular dynamics observation of protein folding transition state
      ensemble.
AB  - The concept of the protein transition state ensemble (TSE), a collection of the
      conformations that have 50% probability to convert rapidly to the folded state
      and 50% chance to rapidly unfold, constitutes the basis of the modern
      interpretation of protein engineering experiments. It has been conjectured that
      conformations constituting the TSE in many proteins are the expanded and
      distorted forms of the native state built around a specific folding nucleus. This
      view has been supported by a number of on-lattice and off-lattice simulations.
      Here we report a direct observation and characterization of the TSE by molecular
      dynamic folding simulations of the C-Src SH3 domain, a small protein that has
      been extensively studied experimentally. Our analysis reveals a set of key
      interactions between residues, conserved by evolution, that must be formed to
      enter the kinetic basin of attraction of the native state.

PMID- 12496120
TI  - Folding pathways of prion and doppel.
AB  - The relevance of various residue positions for the stability and the folding
      characteristics of the prion protein in its normal cellular form are investigated
      by using molecular dynamics simulations of models exploiting the topology of the
      native state. These models allow for reproducing the experimentally validated two
      state behavior of the normal prion isoform. Highly significant correlations are
      found between the most topologically relevant sites in our analysis and the
      single point mutations known to be associated with the arousal of the genetic
      forms of prion disease. Insight into the conformational change is provided by
      comparing the folding process of cellular prion and doppel that share a similar
      native state topology: the folding pathways of the former can be grouped in two
      main classes according to which tertiary structure contacts are formed first
      enroute to the native state. For the latter a single class of pathways leads to
      the native state again through a two-state process. Our results are consistent
      and supportive of the recent experimental findings that doppel lacks the scrapie
      isoform and that such remarkably different behavior involves residues in the
      region containing the two beta-strands and the intervening helix.

PMID- 12496121
TI  - Molecular dynamics simulation of the RNA complex of a double-stranded RNA-binding
      domain reveals dynamic features of the intermolecular interface and its
      hydration.
AB  - The interaction between double-stranded RNA (dsRNA) and the third double-stranded
      domain (dsRBD) from Drosophila Staufen protein represents a paradigm to
      understand how the dsRBD protein family, one of the most common RNA-binding
      protein units, binds dsRNA. The nuclear magnetic resonance (NMR) structure of
      this complex and the x-ray structure of another family member revealed the
      stereochemical basis for recognition, but also raised new questions. Although the
      crystallographic studies revealed a highly ordered interface containing numerous
      water-mediated contacts, NMR suggested extensive residual motion at the
      interface. To address how interfacial motion contributes to molecular recognition
      in the dsRBD-dsRNA system, we conducted a 2-ns molecular dynamics simulation of
      the complex derived from Staufen protein and of the separate protein and RNA
      components. The results support the observation that a high degree of
      conformational flexibility is retained upon complex formation and that this
      involves interfacial residues that are critical for dsRBD-dsRNA binding. The
      structural origin of this residual flexibility is revealed by the analysis of the
      trajectory of motion. Individual basic side chains switch continuously from one
      RNA polar group to another with a residence time seldom exceeding 100 ps, while
      retaining favorable interaction with RNA throughout much of the simulation. Short
      lived water molecules mediate some of these interactions for a large fraction of
      the trajectory studied here. This result indicates that water molecules are not
      statically associated with the interface, but continuously exchange with the bulk
      solvent on a 1-10-ps time scale. This work provides new insight into dsRBD-dsRNA
      recognition and builds upon a growing body of evidence, suggesting that short
      lived dynamic interactions play important roles in protein-nucleic acid
      interactions.

PMID- 12496122
TI  - Labeling proteins via hole burning of their aromatic amino acids: pressure tuning
      spectroscopy of BPTI.
AB  - We demonstrate hole burning on a protein by using an intrinsic aromatic amino
      acid as a probe. The protein is bovine pancreatic trypsin inhibitor (BPTI), the
      labeled amino acid is tyrosine. Only one of the four tyrosines could be burned.
      As an application we present pressure tuning experiments from which the local
      compressibility around the burned tyrosine probe is determined.

PMID- 12496123
TI  - Spectroscopic [correction of eSpectroscopic] and structural properties of valine
      gramicidin A in monolayers at the air-water interface.
AB  - Monomolecular films of valine gramicidin A (VGA) were investigated in situ at the
      air-water interface by x-ray reflectivity and x-ray grazing incidence diffraction
      as well as polarization modulation infrared reflection absorption spectroscopy
      (PM-IRRAS). These techniques were combined to obtain information on the secondary
      structure and the orientation of VGA and to characterize the shoulder observed in
      its pi-A isotherm. The thickness of the film was obtained by x-ray reflectivity,
      and the secondary structure of VGA was monitored using the frequency position of
      the amide I band. The PM-IRRAS spectra were compared with the simulated ones to
      identify the conformation adopted by VGA in monolayer. At large molecular area,
      VGA shows a disordered secondary structure, whereas at smaller molecular areas,
      VGA adopts an anti-parallel double-strand intertwined beta(5.6) helical
      conformation with 30 degrees orientation with respect to the normal with a
      thickness of 25 A. The interface between bulk water and the VGA monolayer was
      investigated by x-ray reflectivity as well as by comparing the experimental and
      the simulated PM-IRRAS spectra on D(2)O and H(2)O, which suggested the presence
      of oriented water molecules between the bulk and the monolayer.

PMID- 12496124
TI  - Picosecond-hetero-FRET microscopy to probe protein-protein interactions in live
      cells.
AB  - By using a novel time- and space-correlated single-photon counting detector, we
      show that fluorescence resonance energy transfer (FRET) between cyan fluorescent
      protein (CFP) and yellow fluorescent protein (YFP) fused to herpes simplex virus
      thymidine kinase (TK) monomers can be used to reveal homodimerization of TK in
      the nucleus and cytoplasm of live cells. However, the quantification of energy
      transfer was limited by the intrinsic biexponential fluorescence decay of the
      donor CFP (lifetimes of 1.3 +/- 0.2 ns and 3.8 +/- 0.4 ns) and by the possibility
      of homodimer formation between two TK-CFP. In contrast, the heterodimerization of
      the transcriptional factor NF-E2 in the nucleus of live cells was quantified from
      the analysis of the fluorescence decays of GFP in terms of 1) FRET efficiency
      between GFP and DsRed chromophores fused to p45 and MafG, respectively, the two
      subunits of NF-E2 (which corresponds to an interchromophoric distance of 39 +/- 1
      A); and 2) fractions of GFP-p45 bound to DsRed-MafG (constant in the nucleus,
      varying in the range of 20% to 70% from cell to cell). The picosecond resolution
      of the fluorescence kinetics allowed us to discriminate between very short
      lifetimes of immature green species of DsRed-MafG and that of GFP-p45 involved in
      FRET with DsRed-MafG.

PMID- 12496125
TI  - Stability of bacteriorhodopsin alpha-helices and loops analyzed by single
      molecule force spectroscopy.
AB  - The combination of high-resolution atomic force microscopy imaging and single
      molecule force spectroscopy allows the identification, selection, and mechanical
      investigation of individual proteins. In a recent paper we had used this
      technique to unfold and extract single bacteriorhodopsins (BRs) from native
      purple membrane patches. We show that subsets of the unfolding spectra can be
      classified and grouped to reveal detailed insight into the individualism of the
      unfolding pathways. We have further developed this technique and analysis to
      report here on the influence of pH effects and local mutations on the stability
      of individual structural elements of BR against mechanical unfolding. We found
      that, although the seven transmembrane alpha-helices predominantly unfold in
      pairs, each of the helices may also unfold individually and in some cases even
      only partially. Additionally, intermittent states in the unfolding process were
      found, which are associated with the stretching of the extracellular loops
      connecting the alpha-helices. This suggests that polypeptide loops potentially
      act as a barrier to unfolding and contribute significantly to the structural
      stability of BR. Chemical removal of the Schiff base, the covalent linkage of the
      photoactive retinal to the helix G, resulted in a predominantly two-step
      unfolding of this helix. It is concluded that the covalent linkage of the retinal
      to helix G stabilizes the structure of BR. Trapping mutant D96N in the M state of
      the proton pumping photocycle did not affect the unfolding barriers of BR.

PMID- 12496126
TI  - Imaging the environment of green fluorescent protein.
AB  - An emerging theme in cell biology is that cell surface receptors need to be
      considered as part of supramolecular complexes of proteins and lipids
      facilitating specific receptor conformations and distinct distributions, e.g., at
      the immunological synapse. Thus, a new goal is to develop bioimaging that not
      only locates proteins in live cells but can also probe their environment. Such a
      technique is demonstrated here using fluorescence lifetime imaging of green
      fluorescent protein (GFP). We first show, by time-correlated single-photon
      counting, that the fluorescence decay of GFP depends on the local refractive
      index. This is in agreement with the Strickler Berg formula, relating the
      Einstein A and B coefficients for absorption and spontaneous emission in
      molecules. We then quantitatively image, by wide-field time-gated fluorescence
      lifetime imaging, the refractive index of the environment of GFP. This novel
      approach paves the way for imaging the biophysical environment of specific GFP
      tagged proteins in live cells.

PMID- 12496127
TI  - Self-diffusion of nonfreezing water in porous carbohydrate polymer systems
      studied with nuclear magnetic resonance.
AB  - Water is an integral part of the structure in biological porous materials such as
      wood and starch. A problem often encountered in the preparation of samples for,
      e.g., electron microscopy is that removal of water leads to a decreasing distance
      between supermolecular structural elements and a distortion of the structure. It
      is, therefore, of interest to find methods to investigate these materials in the
      native water-swollen state. We present a method to study water-swollen biological
      porous structures using NMR to determine the amount and self-diffusion of water
      within the porous objects. The contribution of bulk water to the NMR signal is
      eliminated by performing experiments below the bulk freezing temperature. Further
      decrease of the temperature leads to a gradual freezing of water within the
      porous objects. The contribution of the freezing water fraction to the migration
      of water through the porous network is, thus, estimated. The results are
      rationalized in terms of the ultrastructure of the samples studied, namely, wood
      pulp fibers and potato starch granules.

PMID- 12496128
TI  - Tuning FlaSh: redesign of the dynamics, voltage range, and color of the
      genetically encoded optical sensor of membrane potential.
AB  - The optical voltage sensor FlaSh, made from a fusion of a GFP "reporter domain"
      and a voltage-gated Shaker K(+) channel "detector domain," has been mutagenically
      tuned in both the GFP reporter and channel detector domains. This has produced
      sensors with improved folding at 37 degrees C, enabling use in mammalian
      preparations, and yielded variants with distinct spectra, kinetics, and voltage
      dependence, thus expanding the types of electrical signals that can be detected.
      The optical readout of FlaSh has also been expanded from single wavelength
      fluorescence intensity changes to dual wavelength measurements based on both
      voltage-dependent spectral shifts and changes in FRET. Different versions of
      FlaSh can now be chosen to optimize the detection of either action potentials or
      synaptic potentials, to follow high versus low rates of activity, and to best
      reflect electrical activity in cell types with distinct voltages of operation.

PMID- 12496129
TI  - Glutaraldehyde modified mica: a new surface for atomic force microscopy of
      chromatin.
AB  - We have found that mica surfaces functionalized with aminopropyltriethoxysilane
      and aldehydes bind chromatin strongly enough to permit stable and reliable
      solution imaging by atomic force microscopy. The method is highly reproducible,
      uses very small amounts of material, and is successful even with very light
      degrees of surface modification. This surface is far superior to the widely used
      aminopropyltriethoxysilane-derivatized mica surface and permits resolution of
      structure on the nanometer-scale in an aqueous environment, conditions that are
      particularly important for chromatin studies. For example, bound nucleosomal
      arrays demonstrate major structural changes in response to changes in solution
      conditions, despite their prior fixation (to maintain nucleosome loading) and
      tethering to the surface with glutaraldehyde. By following individual molecules
      through a salt titration in a flow-through cell, one can observe significant
      changes in apparent nucleosome size at lower [salt] and complete loss of DNA from
      the polynucleosomal array at high salt. The latter result demonstrates that the
      DNA component in these arrays is not constrained by the tethering. The former
      result is consistent with the salt-induced loss of histones observed in bulk
      solution studies of chromatin and demonstrates that even histone components of
      the nucleosome are somewhat labile in these fixed and tethered arrays. We foresee
      many important applications for this surface in future atomic force microscopy
      studies of chromatin.

PMID- 12496130
TI  - In situ analysis of spatial relationships between proteins of the nuclear pore
      complex.
AB  - Macromolecular transport between the nucleus and cytoplasm occurs through the
      nuclear pore complexes (NPCs). The NPC in the budding yeast Saccharomyces
      cerevisiae is a 60-MDa structure embedded in the nuclear envelope and composed of
      ~30 proteins, termed nucleoporins or nups. Here we present a large-scale analysis
      of spatial relationships between nucleoporins using fluorescence resonance energy
      transfer (FRET) in living yeast cells. Energy transfer was measured in a panel of
      strains, each of which coexpresses the enhanced cyan and yellow fluorescent
      proteins as fusions to distinct nucleoporins. With this approach, we have
      determined 13 nucleoporin pairs yielding FRET signals. Independent experiments
      are consistent with the FRET results: Nup120 localization is perturbed in the
      nic96-1 mutant, as is Nup82 localization in the nup116Delta mutant. To better
      understand the spatial relationship represented by an in vivo FRET signal, we
      have investigated the requirements of these signals. We demonstrate that in one
      case FRET signal is lost upon insertion of a short spacer between the nucleoporin
      and its enhanced yellow fluorescent protein label. We also show that the Nup120
      FRET signals depend on whether the fluorescent moiety is fused to the N- or C
      terminus of Nup120. Combined with existing data on NPC structure, the FRET pairs
      identified in this study allow us to propose a refined molecular model of the
      NPC. We suggest that the approach may serve as a prototype for the in situ study
      of other large macromolecular complexes.

PMID- 12496131
TI  - Structure of poly(ethylene glycol)-modified horseradish peroxidase in organic
      solvents: infrared amide I spectral changes upon protein dehydration are largely
      caused by protein structural changes and not by water removal per se.
AB  - Fourier transform infrared (FTIR) spectroscopy has emerged as a powerful tool to
      guide the development of stable lyophilized protein formulations by providing
      information on the structure of proteins in amorphous solids. The underlying
      assumption is that IR spectral changes in the amide I and III region upon protein
      dehydration are caused by protein structural changes. However, it has been
      claimed that amide I IR spectral changes could be the result of water removal per
      se. Here, we investigated whether such claims hold true. The structure of
      horseradish peroxidase (HRP) and poly(ethylene glycol)-modified HRP (HRP-PEG) has
      been investigated under various conditions (in aqueous solution, the amorphous
      dehydrated state, and dissolved/suspended in toluene and benzene) by UV-visible
      (UV-Vis), FTIR, and resonance Raman spectroscopy. The resonance Raman and UV-Vis
      spectra of dehydrated HRP-PEG dissolved in neat toluene or benzene were very
      similar to that of HRP in aqueous buffer, and thus the heme environment (heme
      iron spin, coordination, and redox state) was essentially the same under both
      conditions. Therefore, the three-dimensional structure of HRP-PEG dissolved in
      benzene and toluene was similar to that in aqueous solution. The amide I IR
      spectra of HRP-PEG in aqueous buffer and of dehydrated HRP-PEG dissolved in neat
      benzene and toluene were also very similar, and the secondary structure
      compositions (percentages of alpha-helices and beta-sheets) were within the
      standard error the same. These results are irreconcilable with recent claims that
      water removal per se could cause substantial amide I IR spectral changes (M. van
      de Weert, P.I. Haris, W.E. Hennink, and D.J. Crommelin. 2001. Anal. Biochem.
      297:160-169). On the contrary, amide I IR spectral changes upon protein
      dehydration are caused by perturbations in the secondary structure.

PMID- 12496132
TI  - Fluorescence resonance energy transfer-based stoichiometry in living cells.
AB  - Imaging of fluorescence resonance energy transfer (FRET) between fluorescently
      labeled molecules can measure the timing and location of intermolecular
      interactions inside living cells. Present microscopic methods measure FRET in
      arbitrary units, and cannot discriminate FRET efficiency and the fractions of
      donor and acceptor in complex. Here we describe a stoichiometric method that uses
      three microscopic fluorescence images to measure FRET efficiency, the relative
      concentrations of donor and acceptor, and the fractions of donor and acceptor in
      complex in living cells. FRET stoichiometry derives from the concept that
      specific donor-acceptor complexes will give rise to a characteristic FRET
      efficiency, which, if measured, can allow stoichiometric discrimination of
      interacting components. A first equation determines FRET efficiency and the
      fraction of acceptor molecules in complex with donor. A second equation
      determines the fraction of donor molecules in complex by estimating the donor
      fluorescence lost due to energy transfer. This eliminates the need for acceptor
      photobleaching to determine total donor concentrations and allows for repeated
      measurements from the same cell. A third equation obtains the ratio of total
      acceptor to total donor molecules. The theory and method were confirmed by
      microscopic measurements of fluorescence from cyan fluorescent protein (CFP),
      citrine, and linked CFP-Citrine fusion protein, in solutions and inside cells.
      Together, the methods derived from these equations allow sensitive, rapid, and
      repeatable detection of donor-, acceptor-, and donor-acceptor complex
      stoichiometry at each pixel in an image. By accurately imaging molecular
      interactions, FRET stoichiometry opens new areas for quantitative study of
      intracellular molecular networks.

PMID- 12496133
TI  - Atomic force microscopy investigation of fibroblasts infected with wild-type and
      mutant murine leukemia virus (MuLV).
AB  - NIH 3T3 cells were infected in culture with the oncogenic retrovirus, mouse
      leukemia virus (MuLV), and studied using atomic force microscopy (AFM). Cells
      fixed with glutaraldehyde alone, and those postfixed with osmium tetroxide, were
      imaged under ethanol according to procedures that largely preserved their
      structures. With glutaraldehyde fixation alone, the lipid bilayer was removed and
      maturing virions were seen emerging from the cytoskeletal matrix. With osmium
      tetroxide postfixation, the lipid bilayer was maintained and virions were
      observable still attached to the cell surfaces. The virions on the cell surfaces
      were imaged at high resolution and considerable detail of the arrangement of
      protein assemblies on their surfaces was evident. Infected cells were also
      labeled with primary antibodies against the virus env surface protein, followed
      by secondary antibodies conjugated with colloidal gold particles. Other 3T3 cells
      in culture were infected with MuLV containing a mutation in the gPr80(gag) gene.
      Those cells were observed by AFM not to produce normal MuLV on their surfaces, or
      at best, only at very low levels. The cell surfaces, however, became covered with
      tubelike structures that appear to result from a failure of the virions to
      properly undergo morphogenesis, and to fail in budding completely from the cell's
      surfaces.

PMID- 12496134
TI  - Energy of hydrogen bonds probed by the adhesion of functionalized lipid layers.
AB  - It is now well admitted that hydrophobic interactions and hydrogen bonds are the
      main forces driving protein folding and stability. However, because of the
      complex structure of a protein, it is still difficult to separate the different
      energetic contributions and have a reliable estimate of the hydrogen bond part.
      This energy can be quantified on simpler systems such as surfaces bearing
      hydrogen-bonding groups. Using the surface force apparatus, we have directly
      measured the interaction energy between monolayers of lipids whose headgroups can
      establish hydrogen bonds in water: nitrilotriacetate, adenosine, thymidine, and
      methylated thymidine lipids. From the adhesion energy between the surfaces, we
      have deduced the energy of a single hydrogen bond in water. We found in each case
      an energy of 0.5 kcal/mol. This result is in good agreement with recent
      experimental and theoretical studies made on protein systems showing that
      intramolecular hydrogen bonds make a positive contribution to protein
      stabilization.

PMID- 12496135
TI  - Reduced respiratory-related evoked activity in subjects with obstructive sleep
      apnea syndrome.
AB  - Midlatency respiratory-related evoked potentials were measured during wakefulness
      by using a 60-electrode array placed over the cortical region of the scalp. We
      studied the responses evoked by 200-ms pressure pulses at -5 and -10 cmH(2)O
      applied at inspiratory onset and during control tests (no pressure applied) in 14
      subjects with obstructive sleep apnea syndrome (OSAS) and 18 normal subjects.
      Wavelet decomposition was used to smooth and dissect the respiratory-related
      evoked potentials in frequency and time in 8 frequency bands. After denoising,
      selected wavelet scales were used to reconstruct the respiratory-related evoked
      potentials, which were quantified by using global field power estimates. The time
      course of the global field power activity in OSAS subjects compared with normal
      subjects was significantly depressed in the period 55-70 ms poststimulus onset, a
      time when afferent traffic from upper airway receptors arrives in normal
      subjects. The reduced evoked response in subjects with OSAS suggests that these
      subjects receive less afferent input from upper airway mechanoreceptors. This may
      reflect reduced sensitivity of mechanoreceptors or reduced mechanoreceptor
      stimulation due to decreased upper airway compliance during wakefulness in OSAS.

PMID- 12496136
TI  - Upper airway muscle paralysis reduces reflex upper airway motor response to
      negative transmural pressure in rat.
AB  - The reflex upper airway (UA) motor response to UA negative pressure (UANP) is
      attenuated by neuromuscular blockade. We hypothesized that this is due to a
      reduction in the sensitivity of laryngeal mechanoreceptors to changes in UA
      pressure. We examined the effect of neuromuscular blockade on hypoglossal motor
      responses to UANP and to asphyxia in 15 anesthetized, thoracotomized,
      artificially ventilated rats. The activity of laryngeal mechanoreceptors is
      influenced by contractions of laryngeal and tongue muscles, so we studied the
      effect of selective denervation of these muscle groups on the UA motor response
      to UANP and to asphyxia, recording from the pharyngeal branch of the
      glossopharyngeal nerve (n = 11). We also examined the effect of tongue and
      laryngeal muscle denervation on superior laryngeal nerve (SLN) afferent activity
      at different airway transmural pressures (n = 6). Neuromuscular blockade and
      denervation of laryngeal and tongue muscles significantly reduced baseline UA
      motor nerve activity (P < 0.05), caused a small but significant attenuation of
      the motor response to asphyxia, and markedly attenuated the response to UANP.
      Motor denervation of tongue and laryngeal muscles significantly decreased SLN
      afferent activity and altered the response to UANP. We conclude that skeletal
      muscle relaxation reduces the reflex UA motor response to UANP, and this may be
      due to a reduction in the excitability of UA motor systems as well as a decrease
      of the response of SLN afferents to UANP.

PMID- 12496137
TI  - Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling,
      and GLUT-4 content in rat muscles.
AB  - Physical activity is known to increase insulin action in skeletal muscle, and
      data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in
      the molecular mechanisms behind this beneficial effect. 5-Aminoimidazole-4
      carboxamide-1-beta-d-ribofuranoside (AICAR) can be used as a pharmacological tool
      to repetitively activate AMPK, and the objective of this study was to explore
      whether the increase in insulin-stimulated glucose uptake after either long-term
      exercise or chronic AICAR administration was followed by fiber-type-specific
      changes in insulin signaling and/or changes in GLUT-4 expression. Wistar rats
      were allocated into three groups: an exercise group trained on treadmill for 5
      days, an AICAR group exposed to daily subcutaneous injections of AICAR, and a
      sedentary control group. AMPK activity, insulin-stimulated glucose transport,
      insulin signaling, and GLUT-4 expression were determined in muscles characterized
      by different fiber type compositions. Both exercised and AICAR-injected animals
      displayed a fiber-type-specific increase in glucose transport with the most
      marked increase in muscles with a high content of type IIb fibers. This increase
      was accompanied by a concomitant increase in GLUT-4 expression. Insulin signaling
      as assessed by phosphatidylinositol 3-kinase and PKB/Akt activity was enhanced
      only after AICAR administration and in a non-fiber-type-specific manner. In
      conclusion, chronic AICAR administration and long-term exercise both improve
      insulin-stimulated glucose transport in skeletal muscle in a fiber-type-specific
      way, and this is associated with an increase in GLUT-4 content.

PMID- 12496138
TI  - Effect of pedal rate on primary and slow-component oxygen uptake responses during
      heavy-cycle exercise.
AB  - We hypothesized that a higher pedal rate (assumed to result in a greater
      proportional contribution of type II motor units) would be associated with an
      increased amplitude of the O(2) uptake (Vo(2)) slow component during heavy-cycle
      exercise. Ten subjects (mean +/- SD, age 26 +/- 4 yr, body mass 71.5 +/- 7.9 kg)
      completed a series of square-wave transitions to heavy exercise at pedal rates of
      35, 75, and 115 rpm. The exercise power output was set at 50% of the difference
      between the pedal rate-specific ventilatory threshold and peak Vo(2), and the
      baseline power output was adjusted to account for differences in the O(2) cost of
      unloaded pedaling. The gain of the Vo(2) primary component was significantly
      higher at 35 rpm compared with 75 and 115 rpm (mean +/- SE, 10.6 +/- 0.3, 9.5 +/-
      0.2, and 8.9 +/- 0.4 ml. min(-1). W(-1), respectively; P < 0.05). The amplitude
      of the Vo(2) slow component was significantly greater at 115 rpm (328 +/- 29
      ml/min) compared with 35 rpm (109 +/- 30 ml/min) and 75 rpm (202 +/- 38 ml/min)
      (P < 0.05). There were no significant differences in the time constants or time
      delays associated with the primary and slow components across the pedal rates.
      The change in blood lactate concentration was significantly greater at 115 rpm
      (3.7 +/- 0.2 mM) and 75 rpm (2.8 +/- 0.3 mM) compared with 35 rpm (1.7 +/- 0.4
      mM) (P < 0.05). These data indicate that pedal rate influences Vo(2) kinetics
      during heavy exercise at the same relative intensity, presumably by altering
      motor unit recruitment patterns.

PMID- 12496139
TI  - Integration-differentiation and gating of carotid afferent traffic that shapes
      the respiratory pattern.
AB  - The phase-dependent plasticity of carotid chemoafferent signaling was studied
      with electrical stimulation of a carotid sinus nerve during either inspiration or
      expiration in anesthetized, glomectomized, vagotomized, paralyzed, and ventilated
      rats. Stroboscopic and interferometric analyses of the resulting phase-contrast
      disturbances of the respiratory rhythm revealed that carotid chemoafferent
      traffic was dynamically filtered centrally by a parallel bank of leaky
      integrators and differentiators, each being logically gated to the inspiratory or
      expiratory phase in a stop-and-go manner as follows: 1) carotid short-term
      potentiation of inspiratory drive was mediated by dual integrators that both
      shortened inspiration and augmented phrenic motor output cooperatively in long
      and short timescales; 2) carotid short-term depression of respiratory frequency
      was mediated by a (possibly pontine) integrator that lengthened expiration with a
      relatively long memory; and 3) carotid "chemoreflex" shortening of expiration was
      mediated by an occult fast integrator, which, together with carotid short-term
      depression, formed a differentiator. These effects were modulated anteriorly by
      integrators in the nucleus tractus solitarius that were "auto-gated" to, or
      recruited by, the carotid sinus nerve input. Such phase-selective and activity
      dependent time-frequency filtering of carotid chemoafferent feedback in parallel
      neurological-neurodynamic central pathways may profoundly affect respiratory
      stability during hypoxia and sleep and could contribute to the dynamic
      optimization of the respiratory pattern and maintenance of homeostasis in health
      and in disease states.

PMID- 12496140
TI  - N-acetylcysteine infusion alters blood redox status but not time to fatigue
      during intense exercise in humans.
AB  - Infusion of the antioxidant N-acetylcysteine (NAC) reduces fatigability in
      electrically evoked human muscle contraction, but due to reported adverse
      reactions, no studies have investigated NAC infusion effects during voluntary
      exercise in humans. We investigated whether a modified NAC-infusion protocol (125
      mg. kg(-1). h(-1) for 15 min, then 25 mg. kg(-1). h(-1)) altered blood redox
      status and enhanced performance during intense, intermittent exercise. Eight
      untrained men participated in a counterbalanced, double-blind, crossover study in
      which they received NAC or saline (control) before and during cycling exercise,
      which comprised three 45-s bouts and a fourth bout that continued to fatigue, at
      130% peak oxygen consumption. Arterialized venous blood was analyzed for
      glutathione status, hematology, and plasma electrolytes. NAC infusion induced no
      severe adverse reactions. Exercise decreased the reduced glutathione (P < 0.005)
      and increased oxidized glutathione concentrations (P < 0.005); NAC attenuated
      both effects (P < 0.05). NAC increased the rise in plasma K(+) concentration-to
      work ratio (P < 0.05), indicating impaired K(+) regulation, although time to
      fatigue was unchanged (NAC 102 +/- 45 s; saline 107 +/- 53 s). Thus NAC infusion
      altered blood redox status during intense, intermittent exercise but did not
      attenuate fatigue.

PMID- 12496141
TI  - Na+-K+-ATPase alpha 2-gene and skeletal muscle characteristics in response to
      long-term overfeeding.
AB  - The role of Na(+)-K(+)-ATPase alpha2-gene BglII polymorphism in the changes of
      skeletal muscle metabolic properties after a 100-day overfeeding protocol
      conducted with 12 pairs of monozygotic twins is reported. The activities of
      oxoglutarate dehydrogenase (OGDH) and phosphofructokinase (PFK) were determined
      from muscle biopsies. A larger increase in the total fat mass (127 vs. 61%) (P <
      0.05) and low-density lipoprotein cholesterol (20 vs. 0.7%) (P = 0.05) in 8.0/8.0
      kb [3.3-kb negative (-); n = 7 pairs] than in 8.0/3.3 + 3.3/3.3-kb [3.3-kb
      positive (+); n = 5 pairs] subjects was observed. OGDH activity decreased in 3.3
      kb(-) (-15%), whereas PFK (+26%) as well as the PFK-to-OGDH ratio (90%)
      increased. In contrast, among 3.3-kb(+), OGDH increased (+54%) together with a
      decrease in PFK (-1%) and PFK-to-OGDH ratio (-5%). These changes were
      significantly different between genotypes (P from <0.05 to 0.01). In conclusion,
      fat mass, low-density lipoprotein cholesterol, and skeletal muscle glycolytic-to
      oxidative enzyme ratio increased more in the alpha2-gene 3.3-kb(-) subjects with
      overfeeding, suggesting more unfavorable metabolic changes compared with the 3.3
      kb(+) subjects.

PMID- 12496142
TI  - Reduced amount of mitochondrial DNA in aged human muscle.
AB  - Muscle concentrations of mRNAs encoded by mitochondrial DNA (mtDNA) decline with
      aging. To determine whether this can be explained by diminished mtDNA levels, we
      measured the relative concentrations of mtDNA and a representative mtDNA
      transcript [encoding cytochrome-c oxidase, subunit 2 (COX-2)] in muscle of young
      (21-27 yr) and older subjects (65-75 yr). The amount of COX-2 mRNA (relative to
      28S rRNA) was 22% lower (P = 0.04) in older muscle, and the amount of mtDNA
      (relative to nuclear DNA) was 38% lower (P = 0.0002). The average level of
      mitochondrial transcription factor A (Tfam), a protein essential for mtDNA
      replication, was similar in younger and older muscle. Tfam mRNA, nuclear
      respiratory factor-1 mRNA, and several mRNAs encoding proteins required for mtDNA
      replication were expressed at similar levels in younger and older muscle. The
      mtDNA concentrations were only weakly related to age-adjusted aerobic fitness
      (maximal oxygen consumption) and self-reported physical activity levels. We
      conclude that the lower concentration of mitochondrial mRNAs in older muscle can
      be explained by a reduced concentration of mtDNA.

PMID- 12496143
TI  - Molecular pathogenesis of Salmonella enterica serotype typhimurium-induced
      diarrhea.

PMID- 12496144
TI  - Pathogenicity and immune response measured in mice following intranasal challenge
      with enterotoxigenic Escherichia coli strains H10407 and B7A.
AB  - The pathogenicity and immunogenicity induced in BALB/c mice by intranasal (i.n.)
      inoculation of enterotoxigenic Escherichia coli (ETEC) strains H10407
      (O78:H11:CFA/I:LT(+):ST(+)) and B7A (O148:H28:CS6:LT(+):ST(+)) (two ETEC strains
      previously used in human challenge trials) were studied. The i.n. inoculation of
      BALB/c mice with large doses of ETEC strains H10407 and B7A caused illness and
      death. The H10407 strain was found to be consistently more virulent than the B7A
      strain. Following i.n. challenge with nonlethal doses of H10407 and B7A, the
      bacteria were cleared from the lungs of the mice at a steady rate over a 2-week
      period. Macrophages and neutrophils were observed in the alveoli and bronchioles,
      and lymphocytes were observed in the septa, around vessels, and in the pleura of
      the lungs in mice challenged with H10407 and B7A. In mice i.n. challenged with
      H10407, serum immunoglobulin G (IgG) and IgM antibodies were measured at high
      titers to the CFA/I and O78 lipopolysaccharide (LPS) antigens. In mice i.n.
      challenged with B7A, low serum IgG antibody titers were detected against CS6, and
      low serum IgG and IgM antibody titers were detected against O148 LPS. The serum
      IgG and IgM antibody titers against the heat-labile enterotoxin were equivalent
      in the H10407- and B7A-challenged mice. The CFA/I and O78 LPS antigens gave mixed
      T-helper cell 1-T-helper cell 2 (Th1-Th2) responses in which the Th2 response was
      greater than the Th1 response (i.e., stimulated primarily an antibody response).
      These studies indicate that the i.n. challenge of BALB/c mice with ETEC strains
      may provide a useful animal model to better understand the immunogenicity and
      pathogenicity of ETEC and its virulence determinants. This model may also be
      useful in providing selection criteria for vaccine candidates for use in primate
      and human trials.

PMID- 12496145
TI  - Resistance of macrophages to Mycobacterium avium is induced by alpha2-adrenergic
      stimulation.
AB  - The ability of macrophages to control the growth of microorganisms is increased
      by macrophage activation. Previously, it was shown that epinephrine activated
      mouse macrophages to resist the growth of Mycobacterium avium via alpha(2)
      adrenergic stimulation. In the present study, we show that the alpha(2)
      adrenergic agonist (alpha(2)-agonist) clonidine induced resistance to M. avium
      growth in the RAW264.7 mouse macrophage cell line. The ability of catecholamines
      to induce resistance to mycobacteria was specific to alpha(2)-adrenergic
      stimulation, as alpha(1)-, beta(1)-, and beta(2)-agonists had no effect. Receptor
      signaling through Gi proteins was required. A G-protein antagonist specific for
      the alpha subunits of the Go/Gi family blocked the increased resistance induced
      by clonidine, while a Gs-protein antagonist was without effect. Both nitric oxide
      (NO) production and superoxide (O(2)(-)) production were required for the
      increased resistance to M. avium growth induced by clonidine. Although NO
      production was required, clonidine did not increase the level of NO in M. avium
      infected cells. Since NO and O(2)(-) interact to produce peroxynitrite (ONOO(-)),
      we examined whether ONOO(-) mediates the increased resistance to M. avium induced
      by clonidine. 5,10,15,20-Tetrakis(4-sulfonatophenyl)prophyrinato iron (III)
      chloride (FeTPPS), a specific scavenger of ONOO(-), inhibited the effect of
      clonidine on M. avium growth. Clonidine also increased the production of ONOO(-)
      in M. avium-infected RAW264.7 cells, as measured by the oxidation of 123
      dihydrorhodamine and the production of nitrated tyrosine residues. We therefore
      conclude that alpha(2)-adrenergic stimulation activates macrophages to resist the
      growth of M. avium by enhancing the production of ONOO(-).

PMID- 12496146
TI  - Oral immunization with ATP-dependent protease-deficient mutants protects mice
      against subsequent oral challenge with virulent Salmonella enterica serovar
      typhimurium.
AB  - We evaluated the efficacy of mutants with a deletion of the stress response
      protease gene as candidates for live oral vaccine strains against Salmonella
      infection through infection studies with mice by using a Salmonella enterica
      serovar Typhimurium mutant with a disruption of the ClpXP or Lon protease. In
      vitro, the ClpXP protease regulates flagellum synthesis and the ClpXP-deficient
      mutant strain exhibits hyperflagellated bacterial cells (T. Tomoyasu et al., J.
      Bacteriol. 184:645-653, 2002). On the other hand, the Lon protease negatively
      regulates the efficacy of invading epithelial cells and the expression of
      invasion genes (A. Takaya et al., J. Bacteriol. 184:224-232, 2002). When 5-week
      old BALB/c mice were orally administered 5 x 10(8) CFU of the ClpXP- or Lon
      deficient strain, bacteria were detected with 10(3) to 10(4) CFU in the spleen,
      mesenteric lymph nodes, Peyer's patches, and cecum 1 week after inoculation and
      the bacteria then decreased gradually in each tissue. Significant increases of
      lipopolysaccharide-specific immunoglobulin G (IgG) and secretory IgA were
      detected at week 4 and maintained until at least week 12 after inoculation in
      serum and bile, respectively. Immunization with the ClpXP- or Lon-deficient
      strain protected mice against oral challenge with the serovar Typhimurium
      virulent strain. Both the challenged virulent and immunized avirulent salmonellae
      were completely cleared from the spleen, mesenteric lymph nodes, Peyer's patches,
      and even cecum 5 days after the challenge. These data indicate that Salmonella
      with a disruption of the ATP-dependent protease ClpXP or Lon can be useful in
      developing a live vaccine strain.

PMID- 12496147
TI  - Mucosal immunization with helicobacter, CpG DNA, and cholera toxin is protective.
AB  - The mucosal delivery of antigens requires an effective adjuvant to induce mucosal
      immunity. Current mucosal adjuvants include cholera toxin (CT) and Escherichia
      coli heat-labile toxin. Unmethylated CpG immunostimulatory oligodeoxynucleotides
      (ODNs) have been proposed as novel mucosal adjuvants. In this study, mice were
      immunized with sonicated Helicobacter felis with CT and/or CpG ODN adjuvants. All
      groups receiving either adjuvant singly or in combination developed increased
      serum anti-H. felis immunoglobulin G (IgG). The addition of either CpG or CT, or
      both, produced a specific fecal anti-H. felis IgA response, with the highest IgA
      levels occurring in animals immunized intranasally with sonicated H. felis with
      CT and CpG. Following H. felis challenge, addition of the adjuvant CpG ODN
      provided no significant protection, while groups given CT showed a high degree of
      protection, although not complete. When CpG ODN was combined with CT and the
      vaccine combination was delivered intranasally, no bacterial colonization was
      detected by quantitative PCR, providing "sterile immunity" and demonstrating
      synergy between CpG ODN and CT.

PMID- 12496148
TI  - Diversity at the locus associated with transcription of a variable surface
      antigen of Pneumocystis carinii as an index of population structure and dynamics
      in infected rats.
AB  - Pneumocystis carinii expresses a surface glycoprotein called MSG. Different
      isoforms of MSG are encoded by a gene family spread over at least 15 telomeric
      sites. Only one locus, called UCS, supports the production of MSG mRNA. Previous
      studies showed that P. carinii populations from individual rats exhibited high
      degrees of diversity with respect to the MSG genes attached to the UCS locus.
      This diversity could have been generated primarily in the rats studied.
      Alternatively, the rats may have been infected by P. carinii organisms that were
      already different at the UCS locus. To investigate this issue, we examined the
      UCS locus in P. carinii from rats that had been exposed to few of the microbes at
      a specified time, which produced a bottleneck in the microbial population. Some
      of the rats with bottlenecks produced P. carinii populations in which a single
      MSG sequence resided at the UCS locus in 80 to 90% of the organisms, showing that
      P. carinii can proliferate within a rat without generating the very high levels
      of UCS diversity previously seen. From the degree of diversity observed in the
      bottlenecked populations, the maximum rate of switching appeared to be 0.01 event
      per generation. These data also suggest that the infectious dose is as low as one
      organism, that rats that share a cage readily infect each other, and that the
      doubling time of P. carinii in vivo is approximately 3 days. In addition, we
      found that inoculation with 10(7) P. carinii organisms from a population highly
      heterogeneous at the UCS locus reproduced this heterogeneity. By contrast, shifts
      in population structure occurred in rats given 10(4) P. carinii organisms,
      suggesting that a small fraction of these proliferated.

PMID- 12496149
TI  - Interaction of pulmonary surfactant protein C with CD14 and lipopolysaccharide.
AB  - In addition to their effects on alveolar surface tension, some components of lung
      surfactant also have immunological functions. We found recently that the
      hydrophobic lung surfactant protein SP-C specifically binds to the lipid A region
      of lipopolysaccharide (LPS). In this study, we show that SP-C also interacts with
      CD14. Four observations showed cross talk between the three molecules SP-C, LPS,
      and CD14. (i) Like LBP, SP-C allows the binding of a fluorescent LPS to cells
      expressing CD14 (the other surfactant components were ineffective). (ii)
      Recombinant radiolabeled CD14 and SP-C (or a synthetic analog of SP-C) interact
      in a dose-dependent manner. (iii) LPS blocks the binding of radiolabeled CD14 to
      SP-C-coated wells. (iv) SP-C enhances the binding of radiolabeled CD14 to LPS
      coated wells. These results, obtained with native murine SP-C and with three
      synthetic analogs, suggest that LPS and CD14 interact with the same region of SP
      C and that binding of SP-C modifies the conformation of CD14 or the accessibility
      of its LPS-binding site, allowing it to bind LPS. This ability of SP-C to
      interact with the pattern recognition molecule CD14 extends the possible
      immunological targets of SP-C to a large panel of microorganisms that can enter
      the airways.

PMID- 12496150
TI  - Effects of tumor necrosis factor alpha on dendritic cell accumulation in lymph
      nodes draining the immunization site and the impact on the anticryptococcal cell
      mediated immune response.
AB  - Cell-mediated immune (CMI) responses and tumor necrosis factor alpha (TNF-alpha)
      have been shown to be essential in acquired protection against Cryptococcus
      neoformans. Induction of a protective anticryptococcal CMI response includes
      increases in dendritic cells (DC) and activated CD4(+) T cells in draining lymph
      nodes (DLN). During the expression phase, activated CD4(+) T cells accumulate at
      a peripheral site where cryptococcal antigen is injected, resulting in a
      classical delayed-type hypersensitivity (DTH) reaction. Induction of a
      nonprotective anticryptococcal CMI response results in no significant increases
      in the numbers of DC or activated CD4(+) T cells in DLN. This study focuses on
      examining the role of TNF-alpha in induction of protective and nonprotective
      anticryptococcal CMI responses. We found that neutralization of TNF-alpha at the
      time of immunization with the protective immunogen (i) reduces the numbers of
      Langerhans cells, myeloid and lymphoid DC, and activated CD4(+) T cells in DLN
      and (ii) diminishes the total numbers of cells, the numbers of activated CD4(+) T
      cells, and amount of gamma interferon at the DTH reaction site. Although TNF
      alpha neutralization during induction of the nonprotective CMI response had
      little effect on cellular and cytokine parameters measured, it did cause a
      reduction in footpad swelling when mice received challenge in the footpad. Our
      findings show that TNF-alpha functions during induction of the protective CMI
      response by influencing the accumulation of all three DC subsets into DLN.
      Without antigen stimulated DC in DLN, activated CD4(+) T cells are not induced
      and thus not available for the expression phase of the CMI response.

PMID- 12496151
TI  - Both family 1 and family 2 PspA proteins can inhibit complement deposition and
      confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae.
AB  - Pneumococcal surface protein A (PspA), a virulence factor of Streptococcus
      pneumoniae, is exceptionally diverse, being classified into two major families
      which are over 50% divergent by sequence analysis. A family 1 PspA from strain
      WU2 was previously shown to impede the clearance of pneumococci from mouse blood
      and to interfere with complement deposition on the bacterial surface. To
      determine whether a family 2 PspA can perform the same role as family 1 PspA, the
      family 1 PspA (from strain WU2) was replaced with a family 2 PspA (from strain
      TIGR4) by molecular genetic methods to make an isogenic pair of strains
      expressing different PspA proteins. Surface binding of lactoferrin and
      interference with C3 deposition by the two types of PspA proteins were determined
      by flow cytometry, and virulence was assessed in a mouse bacteremia model.
      Although the family 2 PspA appeared to bind less human lactoferrin than did the
      family 1 PspA, both PspA proteins could interfere with complement deposition on
      the pneumococcal surface and could provide full virulence in the mouse infection
      model. A mutant form of the family 2 PspA with a deletion within the choline
      binding region was also produced. Pneumococci with this mutant PspA failed to
      bind human lactoferrin even though the PspA was present on the pneumococcal
      surface. The mutant PspA only partially interfered with complement deposition and
      moderately attenuated virulence. These results suggest that family 1 and family 2
      PspA proteins play similar roles in virulence and that surface accessibility of
      PspA is important for their function.

PMID- 12496152
TI  - Role of Bordetella O antigen in respiratory tract infection.
AB  - Lipopolysaccharide (LPS), as the major surface molecule of gram-negative
      bacteria, interacts with the host in complex ways, both inducing and protecting
      against aspects of inflammatory and adaptive immunity. The membrane-distal
      repeated carbohydrate structure of LPS, the O antigen, can prevent antibody
      functions and may vary as a mechanism of immune evasion. Genes of the wbm locus
      are required for the assembly of O antigen on the animal pathogen Bordetella
      bronchiseptica and the human pathogen B. parapertussis. However, the important
      human pathogen B. pertussis lacks these genes and a number of in vitro and in
      vivo characteristics associated with O antigen in other organisms. To determine
      the specific functions of O antigen in these closely related Bordetella
      subspecies, we compared wbm deletion (Deltawbm) mutants of B. bronchiseptica and
      B. parapertussis in a variety of assays relevant to natural respiratory tract
      infection. Complement was not activated or depleted by wild-type bordetellae
      expressing O antigen, but both Deltawbm mutants activated complement and were
      highly sensitive to complement-mediated killing in vitro. Although the O-antigen
      structures appear to be substantially similar, the two mutants differed
      strikingly in their defects within the respiratory tract. The B. parapertussis
      Deltawbm mutant was severely defective in colonization of the tracheas and lungs
      of mice, while the B. bronchiseptica Deltawbm mutant showed almost no defect.
      While in vitro characteristics such as serum resistance may be attributable to O
      antigen directly, the role of O antigen during infection appears to be more
      complex, possibly involving factors differing among the closely related
      bordetellae or different interactions between each one and its host.

PMID- 12496153
TI  - Antibodies present in normal human serum inhibit invasion of human brain
      microvascular endothelial cells by Listeria monocytogenes.
AB  - Listeria monocytogenes causes meningitis and encephalitis in humans and crosses
      the blood-brain barrier by yet unknown mechanisms. The interaction of the
      bacteria with different types of endothelial cells was recently analyzed, and it
      was shown that invasion into, but not adhesion to, human brain microvascular
      endothelial cells (HBMEC) depends on the product of the inlB gene, the surface
      molecule InlB, which is a member of the internalin multigene family. In the
      present study we analyzed the role of the medium composition in the interaction
      of L. monocytogenes with HBMEC, and we show that invasion of HBMEC is strongly
      inhibited in the presence of adult human serum. The strong inhibitory activity,
      which is not present in fetal calf serum, does not inhibit uptake by macrophage
      like J774 cells but does also inhibit invasion of Caco-2 epithelial cells. The
      inhibitory component of human serum was identified as being associated with L.
      monocytogenes-specific antibodies present in the human serum. Human newborn serum
      (cord serum) shows only a weak inhibitory activity on the invasion of HBMEC by L.
      monocytogenes.

PMID- 12496154
TI  - Oral delivery of Mycobacterium bovis BCG in a lipid formulation induces
      resistance to pulmonary tuberculosis in mice.
AB  - A lipid-based formulation has been developed for oral delivery of Mycobacterium
      bovis bacille Calmette-Guerin (BCG) vaccine. The formulated M. bovis BCG was fed
      to BALB/c mice to test for immune responses and protection against M. bovis
      infection. The immune responses included antigen-specific cytokine responses,
      spleen cell proliferation, and lymphocyte-mediated macrophage inhibition of M.
      bovis. Oral delivery of formulated M. bovis BCG to mice induced strong splenic
      gamma interferon levels and macrophage inhibition of virulent M. bovis compared
      with results with nonformulated M. bovis BCG. Formulated oral M. bovis BCG
      significantly reduced the bacterial burden in the spleen and lungs of mice
      following aerosol challenge with virulent M. bovis. Our data suggest that oral
      delivery of formulated M. bovis BCG is an effective means of inducing protective
      immune responses against tuberculosis. Lipid-based, orally delivered
      mycobacterial vaccines may be a safe and practical method of controlling
      tuberculosis in humans and animals.

PMID- 12496155
TI  - Generation of Helicobacter pylori ghosts by PhiX protein E-mediated inactivation
      and their evaluation as vaccine candidates.
AB  - Bacterial ghosts are empty cell envelopes, which may be generated by the
      controlled expression of the PhiX174 lysis gene E in gram-negative bacteria to
      obtain vaccine candidates. We describe here the application of this technology to
      Helicobacter pylori. The lysis gene cassette was cloned into an Escherichia coli
      Helicobacter pylori shuttle vector and introduced into an H. pylori recipient
      strain by bacterial conjugation. Temperature induction of the lysis gene cassette
      revealed a quantitative killing of the H. pylori culture without induction of
      lysis-resistant bacteria. Biochemical and transmission electron microscopic
      studies identified structurally intact H. pylori. Prophylactic oral vaccination
      experiments using these H. pylori ghosts in the BALB/c mouse model showed a
      significant reduction of the bacterial load in the ghost group, as measured by a
      quantitative bacterial reisolation procedure. Ten of 10 and 5 of 10 mice were
      protected, respectively, without the use of a mucosal adjuvant. Coadministration
      of ghosts with cholera toxin as mucosal adjuvant resulted in a complete
      protection of 10 of 10 and 8 of 8 mice against H. pylori challenge, with three
      animals showing a sterile immunity.

PMID- 12496156
TI  - Effective induction of acquired resistance to Listeria monocytogenes by
      immunizing mice with in vivo-infected dendritic cells.
AB  - Splenic dendritic cells (DCs) obtained from mice at 48 h after Listeria
      monocytogenes infection exhibited up-regulation of CD80 and produced higher
      titers of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) than did DCs
      obtained from uninfected mice. Mice immunized with DCs obtained from mice that
      had been infected with L. monocytogenes 48 h before acquired host resistance to
      lethal infection with L. monocytogenes at 4 and 8 weeks. Immunization with DCs
      from heat-killed L. monocytogenes failed to induce resistance. Acquired
      antilisterial resistance is specific, since the immunized mice could not be
      protected from Salmonella enterica serovar Typhimurium infection. Infected DCs
      stimulated proliferation of naive CD4(+) and CD8(+) cells in vitro, suggesting
      that in vivo-infected DCs activate CD8(+) T cells, which are critical in acquired
      antilisterial resistance, as well as CD4(+) T cells. When wild-type mice were
      immunized with DCs from IFN-gamma-deficient mice, they were protected against a
      lethal L. monocytogenes challenge. In contrast, when mice were immunized with DCs
      from anti-IL-12 p40 monoclonal antibody-injected mice, they failed to gain
      acquired antilisterial resistance. These results suggest that DC-derived IL-12,
      but not IFN-gamma, may play a critical role in induction of acquired
      antilisterial resistance. Our present results suggest that splenic DCs obtained
      from mice infected with L. monocytogenes in vivo may be an effective immunogen
      with which to induce antigen-specific immunity.

PMID- 12496157
TI  - Multigenic control of disease severity after virulent Mycobacterium tuberculosis
      infection in mice.
AB  - Following challenge with virulent Mycobacterium tuberculosis, mice of the I/St
      inbred strain exhibit shorter survival time, more rapid body weight loss, higher
      mycobacterial loads in organs, and more severe lung histopathology than mice of
      the A/Sn strain. We previously performed a genome-wide scan for quantitative
      trait loci (QTLs) that control the severity of M. tuberculosis-triggered disease
      in [(A/Sn x I/St) F1 x I/St] backcross-1 (BC1) mice and described several QTLs
      that are significantly or suggestively linked to body weight loss. In the present
      study we expanded our analysis by including the survival time phenotype and by
      genotyping 406 (A/Sn x I/St) F2 mice for the previously identified chromosomal
      regions of interest. The previously identified 12-cM-wide QTL on distal mouse
      chromosome 3 was designated tbs1 (tuberculosis severity 1); the location of the
      QTL on proximal chromosome 9 was narrowed to a 9-cM interval, and this QTL was
      designated tbs2. Allelic variants of the tbs2 locus appeared to be involved in
      control of both body weight loss and survival time. Also, the data strongly
      suggested that a QTL located in the vicinity of the H-2 complex on chromosome 17
      is involved in control of tuberculosis in mice of both genders, whereas the tbs1
      locus seemed to have an effect on postinfection body weight loss in female mice.
      Interestingly, these loci appeared to interact with each other, which suggests
      that there might be a basic genetic network for the control of intracellular
      parasites. Overall, linkage data reported here for F2 mice are in agreement with,
      and add to, our previous findings concerning the control of M. tuberculosis
      triggered disease in the BC1 segregation.

PMID- 12496158
TI  - The hyaluronic acid capsule of Streptococcus uberis is not required for the
      development of infection and clinical mastitis.
AB  - The frequency at which the genes responsible for capsule biosynthesis occurred in
      field isolates of Streptococcus uberis was determined. Of the two genotypes
      detected (hasABC and hasC), the capsular genotype (hasABC) was more common. This
      genotype was present at a higher frequency in a population isolated from mastitis
      cases than in a population isolated from cattle bedding. The virulence of a
      mutant strain of S. uberis (TRF0-6) that lacked the ability to produce a
      hyaluronic acid capsule due to an insertion within its single copy of hasA (P. N.
      Ward, T. R. Field, W. G. F. Ditcham, E. Maguin, and J. A. Leigh, Infect. Immun.
      69:392-399, 2001) was compared to that of the capsular parental strain (0140J).
      Strains TRF0-6 and 0140J infected all mammary gland quarters following
      experimental challenge. The wild type and the mutant induced overt signs of
      disease in four out of four and in six out of eight mammary gland quarters,
      respectively. Both the wild type and the hasA mutant were resistant to killing by
      bovine neutrophils following cultivation in bovine milk. The ability to withstand
      the bactericidal action of neutrophils following growth in milk was therefore
      independent of the capsule and coincided with the ability of supernatants from
      such cultures to prevent the bactericidal action of neutrophils. This
      investigation revealed that, in the absence of the capsule, S. uberis is able to
      withstand the bactericidal effect of bovine neutrophils and induce mastitis in
      dairy cows.

PMID- 12496159
TI  - Fibronectin bound to the surface of Staphylococcus aureus induces association of
      very late antigen 5 and intracellular signaling factors with macrophage
      cytoskeleton.
AB  - Staphylococcus aureus Cowan I and a clinically isolated coagulase-negative
      Staphylococcus strain, S. saprophyticus 10312, were found to have two fibronectin
      binding proteins, FnBPA and FnBPB. While both staphylococci bound to serum
      fibronectin to a similar extent, fibronectin binding significantly increased the
      phagocytic activity of macrophages against S. aureus (by ca. 150%) but not
      against S. saprophyticus. This enhancing effect of fibronectin was inhibited by
      an RGD sequence-containing peptide and also by anti-very late antigen 5 antibody.
      This suggests that the effect is mediated by very late antigen 5 expressed on
      macrophages. In macrophages ingesting fibronectin-bound Cowan I, alpha(5) and
      beta(1) chains were associated with the cytoskeleton. Cytosolic signaling factors
      such as paxillin, c-Src, and c-Csk were also associated with the cytoskeleton. On
      the contrary, beta(3) integrin transiently disappeared from the cytoskeleton when
      macrophages ingested the fibronectin-treated S. aureus Cowan I. Furthermore, the
      Src kinase family tyrosine kinase Lyn dissociated from the cytoskeleton. These
      cellular components did not respond in a fibronectin-dependent manner when
      macrophages phagocytosed S. saprophyticus. This means that only fibronectin
      treated S. aureus Cowan I induces the accumulation of very late antigen 5, which
      in turn induces the association of paxillin and tyrosine kinases. It is thought
      that the phagocytic activity of macrophages against fibronectin-treated S. aureus
      was increased by signaling via the activation of very late antigen 5.

PMID- 12496160
TI  - Role of S-layer protein antigenic diversity in the immune responses of sheep
      experimentally challenged with Campylobacter fetus subsp. fetus.
AB  - Surface layer proteins (SLPs) are essential for induction of abortion by
      Campylobacter fetus subsp. fetus in experimentally challenged ewes. These
      proteins are encoded by multiple sap genes and vary in size and antigenicity. The
      role of SLP antigenic variation during experimental ovine infection was
      investigated. Following subcutaneous challenge, the SLPs were highly antigenic,
      and antibodies were detected in serum, milk, bile, and urine. Fecal anti-SLP
      antibodies were detected only in animals challenged orally. Ewes challenged with
      wild-type strain 23D with variable SLPs developed detectable circulating anti-SLP
      immunoglobulin G (IgG) antibodies by 2 weeks postchallenge. In contrast, ewes
      challenged with mutants of 23D that had fixed expression of a single SLP
      developed antibodies within 1 week postchallenge, suggesting that antigenic
      variation in SLPs may delay the host antibody response. Although not
      statistically significant, the data from challenge experiments in which
      vaccinated ewes were used suggested that SLP-expressing vaccines could protect
      animals from abortion and that this effect was independent of the SLP expressed,
      indicating involvement of conserved epitopes in the SLP. The conserved 184-amino
      acid N-terminal region of the SLP, identified from previously published
      sequences, was epitope mapped with rabbit anti-SLP antisera by using overlapping
      synthetic 20-mer peptides. Two putative epitopes were identified at amino acids
      81 to 110 and 141 to 160. Amino acids 81 to 100 also bound serum IgG antibodies
      from experimentally challenged sheep. Conserved antigenic regions of the SLP that
      induce protective immune responses may enable development of synthetic vaccine
      candidates for C. fetus subsp. fetus-associated ovine abortion.

PMID- 12496161
TI  - Lipooligosaccharide-deficient Neisseria meningitidis shows altered pilus
      associated characteristics.
AB  - Molecular interaction between host mucosal surfaces and outer membrane components
      of microbes is crucial in the infection process. The outer membrane of pathogenic
      Neisseria contains surface molecules such as pili, PilC, and Opa and a monolayer
      of lipooligosaccharide (LOS), all of which are involved in the interaction with
      host cells. Pili mediate the initial attachment to human epithelial cells, which
      is followed by tight contact between bacteria and the eucaryotic cells, leading
      to bacterial invasion. To further examine the basis for bacterium-host cell
      contact, we constructed an LOS-deficient Neisseria meningitidis serogroup C
      mutant. LOS deficiency was without exception accompanied by altered colony
      opacity and morphology, which most likely represented an "on" switch for Opa540
      expression, and by reduced levels of the iron-regulated proteins FetA and FbpA.
      We show here that LOS is essential for pilus-associated adherence but dispensable
      for fiber formation and twitching motility. The absence of attachment to
      epithelial cells could not be attributed to altered levels of piliation or
      defects in the pilus adhesion phenotype. Further, LOS mutants do not invade host
      cells and have lost the natural competence for genetic transformation.

PMID- 12496162
TI  - Two-component systems in Haemophilus influenzae: a regulatory role for ArcA in
      serum resistance.
AB  - Knockout mutations were constructed in the arcA gene of a virulent type b strain
      of Haemophilus influenzae, and the behavior of the resulting mutants was
      investigated in a number of conditions that mimicked distinct steps in the
      natural infection pathway. In arcA mutants, synthesis of capsule and
      lipooligosaccharide (LOS) and growth in synthetic media were unaltered compared
      to synthesis of capsule and LOS and growth in synthetic media in the wild-type H.
      influenzae type b parent strain. However, the virulence of the arcA mutants for
      BALB/c mice was significantly reduced. Upon exposure to human blood or serum, the
      arcA mutants showed markedly reduced survival compared with the survival of its
      wild-type parent. Serum resistance could be fully restored by complementation in
      cis with the H. influenzae arcA gene but not by complementation in cis with the
      homologous gene from Escherichia coli. The proteomes of wild-type and mutant
      bacteria were markedly different, especially under anaerobic conditions,
      underscoring the global regulatory role of ArcAB in H. influenzae. Evaluation of
      antibody titers and classical complement activities in various serum samples
      pointed to complement-mediated bactericidal activity as the factor that
      distinguishes between the arcA mutant and wild-type phenotypes. Comparative
      analysis of the membrane fractions of the arcA mutants and the wild-type strain
      revealed several ArcA-regulated proteins, some of which may be implicated in the
      serum hypersensitivity phenotype.

PMID- 12496163
TI  - Superoxide dismutase influences the virulence of Cryptococcus neoformans by
      affecting growth within macrophages.
AB  - Superoxide dismutase (SOD) is an enzyme that converts superoxide radicals into
      hydrogen peroxide and molecular oxygen and has been shown to contribute to the
      virulence of many human-pathogenic bacteria through its ability to neutralize
      toxic levels of reactive oxygen species generated by the host. SOD has also been
      speculated to be important in the pathogenesis of fungal infections, but the role
      of this enzyme has not been rigorously investigated. To examine the contribution
      of SOD to the pathogenesis of fungal infections, we cloned the Cu,Zn SOD-encoding
      gene (SOD1) from the human-pathogenic yeast Cryptococcus neoformans and made
      mutants via targeted disruption. The sod1 mutant strains had marked decreases in
      SOD activity and were strikingly more susceptible to reactive oxygen species in
      vitro. A sod1 mutant was significantly less virulent than the wild-type strain
      and two independent reconstituted strains, as measured by cumulative survival in
      the mouse inhalational model. In vitro studies established that the sod1 strain
      had attenuated growth compared to the growth of the wild type and a reconstituted
      strain inside macrophages producing reduced amounts of nitric oxide. These
      findings demonstrate that (i) the Cu,Zn SOD contributes to virulence but is not
      required for pathogenicity in C. neoformans; (ii) the decreased virulence of the
      sod1 strain may be due to increased susceptibility to oxygen radicals within
      macrophages; and (iii) other antioxidant defense systems in C. neoformans can
      compensate for the loss of the Cu,Zn SOD in vivo.

PMID- 12496164
TI  - Purification and characterization of a UDP-glucosyltransferase produced by
      Legionella pneumophila.
AB  - Legionella pneumophila is the agent of Legionnaires' disease. It invades and
      replicates within eukaryotic cells, including aquatic protozoans, mammalian
      macrophages, and epithelial cells. The molecular mechanisms of the Legionella
      interaction with target cells are not fully defined. In an attempt to discover
      novel virulence factors of L. pneumophila, we searched for bacterial enzymes with
      transferase activity. Upon screening ultrasonic extracts of virulent legionellae,
      we identified a uridine diphospho (UDP)-glucosyltransferase activity, which was
      capable of modifying a 45-kDa substrate in host cells. An approximately 60-kDa
      UDP-glucosyltransferase was purified from L. pneumophila and subjected to
      microsequencing. An N-terminal amino acid sequence, as well as the sequence of an
      internal peptide, allowed us to identify the gene for the enzyme within the
      unfinished L. pneumophila genome database. The intact gene was cloned and
      expressed in Escherichia coli, and the recombinant protein was purified and
      confirmed to possess an enzymatic activity similar to that of the native UDP
      glucosyltransferase. We designated this gene ugt (UDP-glucosyltransferase). The
      Legionella enzyme did not exhibit significant homology with any known protein,
      suggesting that it is novel in structure and, perhaps, in function. Based on PCR
      data, an enzyme assay, and an immunoblot analysis, the glucosyltransferase
      appeared to be conserved in L. pneumophila strains but was absent from the other
      Legionella species. This study represents the first identification of a UDP
      glucosyltransferase in an intracellular parasite, and therefore modification of a
      eukaryotic target(s) by this enzyme may influence host cell function and promote
      L. pneumophila proliferation.

PMID- 12496165
TI  - Molecular heterogeneity of Ehrlichia chaffeensis isolates determined by sequence
      analysis of the 28-kilodalton outer membrane protein genes and other regions of
      the genome.
AB  - Ehrlichia chaffeensis, a tick-transmitted rickettsial agent, is responsible for
      human monocytic ehrlichiosis (HME). In this study, we genetically mapped 10
      isolates obtained from HME patients. Sequence analysis of the 28-kDa outer
      membrane protein (OMP) multigene locus spanning 6 of the 22 tandemly arranged
      genes identified three distinct genetic groups with shared homology among
      isolates within each group. Isolates in Groups I and III contained six genes
      each, while Group II isolates had a gene deletion. There were two regions on the
      locus where novel gene deletion or insertion mutations occurred, resulting in the
      net loss of one gene in Group II isolates. Numerous nucleotide differences among
      genes in isolates of each group also were detected. The shared homology among
      isolates in each group for the 28-kDa OMP locus suggests the derivation of clonal
      lineages. Transcription and translation analysis of the locus revealed
      differences in the expressed genes of different group isolates. Analysis of the
      120-kDa OMP gene and variable-length PCR target gene showed size variations
      resulting from loss or gain of long, direct repeats within the protein coding
      sequences. To our knowledge this is the first study that looked at several
      regions of the genome simultaneously, and we provide the first evidence of
      heterogeneity resulting from gene deletion and insertion mutations in the E.
      chaffeensis genome. Diversity in different genomic regions could be the result of
      a selection process or of independently evolved genes.

PMID- 12496166
TI  - 4-1BB (CD137) differentially regulates murine in vivo protein- and polysaccharide
      specific immunoglobulin isotype responses to Streptococcus pneumoniae.
AB  - 4-1BB (CD137) is induced on activated CD4(+) and CD8(+) T cells and delivers a
      costimulatory signal upon binding the 4-1BB ligand (4-1BBL) expressed on antigen
      presenting cells. Induction of 4-1BB is dependent on activation via the T-cell
      receptor (TCR) and possibly CD28. It was previously demonstrated that both an in
      vivo protein (pneumococcal surface protein A [PspA])- and polysaccharide
      (phosphorylcholine [PC] determinant of teichoic acid)-specific immunoglobulin
      (Ig) isotype response to Streptococcus pneumoniae was dependent on CD4(+)
      TCRalphabeta(+) T cells and B7-dependent costimulation through CD28. We thus
      postulated that 4-1BB costimulation would also play a role in regulating the in
      vivo anti-PspA and anti-PC response to S. pneumoniae. We demonstrate that mice
      genetically deficient in 4-1BBL elicit a markedly reduced IgM and IgG anti-PC but
      normal primary and secondary IgG anti-PspA responses to S. pneumoniae relative to
      those for wild-type mice. However, injection of an agonistic anti-4-1BB
      monoclonal antibody (MAb), while having no significant effect on the anti-PC
      response, strongly inhibits the primary anti-PspA response, the generation of
      PspA-specific memory, and germinal center formation but does not induce a lasting
      state of tolerance. In contrast, anti-4-1BB MAb has no effect on the anti-PspA
      response when injected only at the time of secondary immunization. Delay of the
      addition of anti-4-1BB leads to progressively less inhibition of the primary
      response up to day 8. This inhibition is independent of CD8(+) T cells and is
      associated with the expansion of CD4(+) T cells with an activated phenotype,
      which is partly dependent on B7-dependent costimulation. These data are the first
      to suggest a stimulatory role for endogenous 4-1BB-4-1BBL interactions during a
      humoral immune response to a pathogen and further underscore significant
      differences in costimulation requirements for an in vivo protein- versus
      polysaccharide-specific Ig isotype response to an extracellular bacterium.

PMID- 12496167
TI  - Phagocyte NADPH oxidase, but not inducible nitric oxide synthase, is essential
      for early control of Burkholderia cepacia and chromobacterium violaceum infection
      in mice.
AB  - Reactive oxygen and nitrogen intermediates have critical, partially overlapping
      roles in host defense against a variety of pathogens. Using mice deficient in
      generating phagocyte superoxide (p47(phox)(-/-)) and mice deficient in generating
      inducible nitric oxide synthase (iNOS(-/-)), we examined the roles of these
      reactive species in host defense against Burkholderia cepacia and Chromobacterium
      violaceum, organisms known to have unusual virulence in chronic granulomatous
      disease. Intraperitoneal B. cepacia challenge (4.0 x 10(3) to 4.0 x 10(5)
      organisms/mouse) resulted in mortality in all p47(phox)(-/-) mice, with the
      survival interval being inversely proportionate to the amount of inoculum.
      Pretreatment with gamma interferon did not affect survival. C. violaceum was
      strikingly virulent in p47(phox)(-/-) mice (the 50% lethal dose [LD(50)] was <13
      organisms). iNOS(-/-) and wild-type mice were resistant to B. cepacia challenges
      of at least 10(6) organisms per mouse, and the LD(50) of C. violaceum was between
      10(6) and 10(7) organisms per mouse. Consistent with the survival data, numbers
      of organisms in cultures of B. cepacia from multiple sites were higher for
      p47(phox)(-/-) mice than for iNOS(-/-) and wild-type mice at day 4 after
      challenge, but numbers of organisms for different B. cepacia strains varied. The
      recovery of C. violaceum was strikingly greater at 18 h after challenge for
      p47(phox)(-/-) mice than for iNOS(-/-) and wild-type mice, in which the organism
      burdens were virtually nil. In vitro, both B. cepacia and C. violaceum were
      sensitive to H(2)O(2) and to reactive nitrogen intermediates but the
      sensitivities of different strains varied significantly. Host defense against B.
      cepacia and C. violaceum is critically dependent in vivo on reactive oxygen
      intermediates, and these species are model organisms to further dissect host and
      pathogen interactions related to the generation and scavenging of microbicidal
      reactive intermediates.

PMID- 12496168
TI  - Cleavage of antigen-bound immunoglobulin G by SpeB contributes to streptococcal
      persistence in opsonizing blood.
AB  - Group A streptococci (GAS) express a superantigen, SpeB, having cysteine protease
      activity. SpeB exhibits several properties that might contribute to virulence,
      the most recently discovered being the ability to cleave immunoglobulin G (IgG)
      in a manner similar to that of papain. In the present study, we confirmed this
      latter finding and found that the irreversible inhibition of SpeB protease
      activity completely abolishes IgG cleavage. SpeB cleavage of IgG was not species
      restricted since SpeB cleaved both human, rabbit, and mouse IgG. In order to
      investigate the nature of the SpeB cleavage of IgG, antibodies were immobilized
      prior to exposure to SpeB, either by unspecific binding of the Fc to GAS surface
      proteins or by antigen-specific binding. Analysis of the IgG molecules by SDS
      PAGE showed that SpeB could cleave antigen-bound antibodies, while the IgG bound
      to IgG-binding proteins was protected from cleavage. In a phagocytosis assay
      using whole blood, the M49 GAS strain NZ131 showed a significantly higher
      survival than its isogenic speB mutant. Furthermore, the addition of
      extracellular supernatant derived from an overnight culture of native NZ131
      increased the survival of its isogenic speB derivative. This indicates that
      SpeB's ability to cleave off the Fc part of antigen-bound IgG contributes to GAS
      escape from opsonophagocytosis while not interfering with the formation of a host
      like coat by unspecific IgG binding.

PMID- 12496169
TI  - Genetic alteration of capsule type but not PspA type affects accessibility of
      surface-bound complement and surface antigens of Streptococcus pneumoniae.
AB  - The Streptococcus pneumoniae capsular polysaccharides and pneumococcal surface
      protein A (PspA) are major determinants of virulence that are antigenically
      variable and capable of eliciting protective immune responses. By genetically
      switching the pspA genes of the capsule type 2 strain D39 and the capsule type 3
      strain WU2, we showed that the different abilities of antibody to PspA to protect
      against these strains was not related to the PspA type expressed. Similarly, the
      level of specific antibody binding to PspA, other surface antigens, and surface
      localized C3b did not depend on the PspA type but instead was correlated with the
      capsule type. The type 3 strain WU2 and an isogenic derivative of D39 that
      expresses the type 3 capsule bound nearly identical amounts of antibody to PspA
      and other surface antigens, and these amounts were less than one-half the amount
      observed with the type 2 parent strain D39. Expression of the type 3 capsule in
      D39 also reduced the amount of C3b deposited and its accessibility to antibody,
      resulting in a level intermediate between the levels observed with WU2 and D39.
      Despite these effects, the capsule type was not the determining factor in anti
      PspA-mediated protection, as both D39 and its derivative expressing the type 3
      capsule were more resistant to protection than WU2. The specific combination of
      PspA and capsule type also did not determine the level of protection. The capsule
      structure is thus a major determinant in accessibility of surface antigens to
      antibody, but certain strains appear to express other factors that can influence
      antibody-mediated protection.

PMID- 12496170
TI  - Induction of osteoclastogenesis and matrix metalloproteinase expression by the
      lipooligosaccharide of Treponema denticola.
AB  - Alveolar bone destruction is a characteristic feature of periodontitis. Treponema
      denticola is known to be involved in periodontitis. To elucidate the role of T.
      denticola in alveolar bone destruction in periodontitis, the effects of
      lipooligosaccharide (LOS) from T. denticola on osteoclast formation and on
      expression of osteoclast differentiation factor (ODF) and osteoprotegerin (OPG)
      mRNAs were examined in a coculture system by using mouse calvaria and bone marrow
      cells. In addition, the effect of T. denticola LOS on expression of matrix
      metalloproteinases (MMPs), which are involved in bone resorption, was estimated
      in mouse calvaria-derived osteoblastic cells. When the mouse calvaria and bone
      marrow cells were challenged with LOS (0.1 to 10 micro g/ml) for 4 days, the
      number of tartrate-resistant acid phosphatase-positive multinucleated cells
      increased in a dose-dependent manner. The expression of ODF mRNA increased, while
      OPG mRNA expression decreased. Polymyxin B changed the effect of LOS (10 micro
      g/ml) on ODF and OPG mRNA expression to the control level. LOS (10 micro g/ml)
      stimulated prostaglandin E(2) (PGE(2)) production in the cocultures. Adding
      indomethacin, an inhibitor of prostaglandin synthesis, resulted in a reduction in
      the number of osteoclasts induced by LOS and eliminated the effect of T.
      denticola LOS on ODF and OPG mRNA expression. T. denticola LOS increased the
      levels of mRNAs encoding MMP-3, -8, -9, -10, -13, and -14. Expression of one of
      these mRNAs, MMP-9 mRNA, was significantly induced by T. denticola LOS. These
      findings suggest that LOS from T. denticola stimulates osteoclastogenesis and MMP
      expression. Up-regulation of ODF and down-regulation of OPG by a PGE(2)-dependent
      mechanism were involved in the osteoclastogenesis induced by T. denticola LOS.

PMID- 12496171
TI  - Seeligeriolysin O, a cholesterol-dependent cytolysin of Listeria seeligeri,
      induces gamma interferon from spleen cells of mice.
AB  - Seeligeriolysin O (LSO), one of the cholesterol-dependent cytolysins produced by
      Listeria seeligeri, shows 80% homology to listeriolysin O (LLO) produced by
      Listeria monocytogenes at the amino acid sequence level. In addition to cytolytic
      activity, LLO has been shown to exhibit cytokine-inducing activity. In order to
      determine whether LSO is also capable of exhibiting these two different
      activities, we constructed a recombinant full-length LSO (rLSO530) and a
      noncytolytic truncated derivative with a C-terminal deletion (rLSO483) and
      compared these molecules with recombinant LLO. The cytolytic rLSO530 molecule
      could induce gamma interferon (IFN-gamma) production in spleen cells when the
      cytolytic activity was blocked by treatment with cholesterol. The noncytolytic
      truncated rLSO483 molecule also induced IFN-gamma production. Anti-LLO polyclonal
      antibody inhibited not only LLO-induced IFN-gamma production but also LSO-induced
      IFN-gamma production. Both NK cells and CD11b(+) cells were required for LSO
      induced IFN-gamma production. Among the various cytokines expressed in CD11b(+)
      cells, interleukin-12 (IL-12) and IL-18 appeared to be essential. We concluded
      that LSO exhibits the same biological activity as LLO.

PMID- 12496172
TI  - Identification of substrates and chaperone from the Yersinia enterocolitica 1B
      Ysa type III secretion system.
AB  - All pathogenic Yersinia enterocolitica strains carry the pYV plasmid encoding the
      Ysc-Yop type III secretion (TTS) system, which operates at 37 degrees C. In
      addition, biovar 1B Y. enterocolitica strains possess a second, chromosomally
      encoded, TTS system called Ysa, which operates, at least in vitro, under low
      temperature and high-salt (LTHS) conditions. Six open reading frames, sycB, yspB,
      yspC, yspD, yspA, and acpY, neighbor the ysa genes encoding the Ysa TTS
      apparatus. Here we show that YspA, YspB, YspC, and YspD are secreted by the Ysa
      TTS system under LTHS conditions. SycB is a chaperone for YspB and YspC and
      stabilizes YspB. YspB, YspC, and SycB share some similarity with TTS substrates
      and the chaperone encoded by the Mxi-Spa locus of Shigella flexneri and SPI-1 of
      Salmonella enterica. In addition, Ysa also secretes the pYV-encoded YopE under
      LTHS conditions, indicating that YopE is a potential effector of both Y.
      enterocolitica TTS systems. YspC could also be secreted by S. flexneri, but no
      functional complementation of ipaC was observed, which indicates that despite
      their similarity the Ysa and the Mxi-Spa systems are not interchangeable. When
      expressed from the yopE promoter, YspB and YspC could also be secreted via the
      Ysc injectisome. However, they could not form detectable pores in eukaryotic
      target cells and could not substitute for YopB and YopD for translocation of Yop
      effectors.

PMID- 12496173
TI  - THP-1 cell apoptosis in response to Mycobacterial infection.
AB  - We previously reported that Mycobacterium tuberculosis infection primes human
      alveolar macrophages (HAM) for tumor necrosis factor alpha (TNF-alpha)-mediated
      apoptosis and that macrophage apoptosis is associated with killing internalized
      bacilli. Virulent mycobacterial strains elicit much less apoptosis than
      attenuated strains, implying that apoptosis is a defense against intracellular
      infection. The present study evaluated the potential for phorbol myristate
      acetate-differentiated THP-1 cells to mimic this response of primary macrophages.
      Consistent with the behavior of alveolar macrophages, attenuated M. tuberculosis
      H37Ra and Mycobacterium bovis BCG strongly induce THP-1 apoptosis, which requires
      endogenous TNF. THP-1 apoptosis is associated with reduced viability of infecting
      BCG. In contrast, virulent wild-type M. tuberculosis H37Rv and M. bovis do not
      increase THP-1 apoptosis over baseline. BCG induced early activation of caspase
      10 and 9, followed by caspase 3. In contrast, wild-type M. bovis infection failed
      to activate any caspases in THP-1 cells. BCG-induced THP-1 apoptosis is blocked
      by retroviral transduction with vectors expressing crmA but not bcl-2. We
      conclude that differentiated THP-1 cells faithfully model the apoptosis response
      of HAM. Analysis of the THP-1 cell response to infection with virulent
      mycobacteria suggests that TNF death signals are blocked proximal to initiator
      caspase activation, at the level of TNF receptor 1 or its associated
      intracytoplasmic adaptor complex. Interference with TNF death signaling may be a
      virulence mechanism that allows M. tuberculosis to circumvent innate defenses
      leading to apoptosis of infected host cells.

PMID- 12496174
TI  - Entry of the lymphogranuloma venereum strain of Chlamydia trachomatis into host
      cells involves cholesterol-rich membrane domains.
AB  - Chlamydiae are bacterial pathogens which develop strictly inside the epithelial
      cells of their hosts. The mechanism used by chlamydiae to enter cells is not well
      characterized; however, it is thought to consist of a receptor-mediated process.
      In addition, the formation of clathrin-coated pits appears to be dispensable for
      chlamydiae to be internalized by host cells. Clathrin-independent endocytosis has
      recently been shown to occur through cholesterol-rich lipid microdomains, which
      are characterized by detergent insolubility. In the present study, we
      investigated whether these lipid domains play a role in Chlamydia trachomatis
      serovar L2 internalization by host cells. Our results show that after binding to
      HeLa cells, chlamydiae are associated with detergent-resistant lipid microdomains
      (DRMs), which can be isolated by fractionation of infected HeLa cells and
      flotation on a sucrose gradient. After internalization by HeLa cells, chlamydiae
      were still found in DRMs. In addition, extraction of plasma membrane cholesterol
      inhibited infection of HeLa cells by C. trachomatis. Many of the proteins
      associated with DRMs are glycosylphosphatidylinositol (GPI)-anchored proteins;
      however, our results could not identify a role for GPI-anchored proteins in the
      entry process. The same results were obtained for Chlamydia psittaci strain GPIC.
      We propose that cholesterol-rich domains participate in the entry of chlamydiae
      into host cells. Chlamydia binding to cholesterol-rich domains may lead to
      coalescence of the bacterial cells, which could trigger internalization by host
      cells.

PMID- 12496175
TI  - Placental tumor necrosis factor alpha but not gamma interferon is associated with
      placental malaria and low birth weight in Malawian women.
AB  - Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW).
      We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF
      alpha) and gamma interferon (IFN-gamma) in these adverse outcomes. We measured
      cytokine concentrations in placental, peripheral, and cord blood plasma in
      relation to malaria parasitemia and placental monocyte accumulation in 276
      Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus
      status, and infant birth weight were determined. Concentrations of TNF-alpha in
      placental blood were correlated with densities of Plasmodium falciparum-infected
      erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001)
      on placental histology. Peripheral blood TNF-alpha concentrations were relatively
      low and were weakly associated with malaria. TNF-alpha concentrations were higher
      in placental blood, where they were strongly associated with malaria. Placental
      plasma TNF-alpha levels were higher in women who had LBW babies (P = 0.0027),
      women with febrile symptoms (P < 0.0001), and teenage mothers (P = 0.04) than in
      other women. The presence of TNF-alpha in cord blood was not associated with
      malaria infection. IFN-gamma levels were infrequently elevated, and elevated IFN
      gamma levels were not associated with poor pregnancy outcomes. Placental
      production of TNF-alpha, but not of IFN-gamma, may be implicated in impaired
      fetal growth in Malawian women.

PMID- 12496176
TI  - Interleukin-1 receptor antagonist gene polymorphism, vaginal interleukin-1
      receptor antagonist concentrations, and vaginal ureaplasma urealyticum
      colonization in pregnant women.
AB  - Ureaplasma urealyticum is the microorganism most frequently isolated from
      amniotic fluids of women in preterm labor. The relationship between vaginal
      colonization with U. urealyticum, vaginal interleukin-1 receptor antagonist (IL
      1ra) levels, and the IL-1ra genotype in pregnant women was examined. Vaginal
      specimens, obtained with a cotton swab from 207 women in their first trimester of
      pregnancy, were tested for IL-1ra concentrations by enzyme-linked immunosorbent
      assay and for U. urealyticum and IL-1ra genotypes by PCR. U. urealyticum was
      detected in 85 (41.1%) women. The median IL-1ra level was 450 ng/ml in women
      positive for U. urealyticum, as opposed to 225 ng/ml in women negative for this
      microorganism (P < 0.0001). Sixty-two percent of the 16 women who were homozygous
      for allele 2 of the IL-1ra gene (IL-1RN*2) were colonized with U. urealyticum, as
      opposed to 47% of the 49 women who were IL-1RN*1/IL-1RN*2 heterozygotes and 34%
      of the 133 women who were IL-1RN*1 homozygotes (P < 0.05). Median IL-1ra levels
      were 750 ng/ml in IL-1RN*2 homozygotes, 300 ng/ml in IL-1RN*1/IL-1RN*2
      heterozygotes, and 250 ng/ml in IL-1RN*1 homozygotes (P = 0.02). The vast
      majority of subjects had an uneventful pregnancy and delivered a healthy infant
      at term. The IL-1ra genotype or U. urealyticum colonization was unrelated to
      birth weight. Pregnant women who are colonized with U. urealyticum during the
      first trimester have elevated vaginal IL-1ra concentrations and a higher
      prevalence of the IL-1RN*2 homozygote genotype than do noncolonized women.

PMID- 12496177
TI  - Age-related disparity in functional activities of human group C serum
      anticapsular antibodies elicited by meningococcal polysaccharide vaccine.
AB  - Serum bactericidal activity confers protection against meningococcal disease, but
      it is not known whether vaccine-induced anticapsular antibodies that lack
      bactericidal activity are protective. We developed an infant rat challenge model
      using a naturally occurring O-acetylated strain of Neisseria meningitidis group C
      and a strain that was negative for O acetylation (OAc). Rats 4 to 7 days of age
      inoculated intraperitoneally (i.p.) with approximately 10(3) CFU of either strain
      developed >5 x 10(5) CFU/ml of blood obtained 18 h later. Dilutions of
      preimmunization sera given i.p. 2 h before the bacterial challenge had no effect
      on bacteremia, whereas group C anticapsular antibody in sera from adults
      immunized with meningococcal polysaccharide vaccine conferred complete or partial
      (>99% decrease in CFU per milliliter of blood) protection against the OAc
      positive or OAc-negative strain, respectively, at antibody doses as low as 0.04
      micro g/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 micro
      g/rat) in pooled sera from children immunized at a mean age of 2.6 years failed
      to protect rats, but antibody at the same or fivefold-lower dose in a serum pool
      from a group of children immunized at 4 years of age gave complete or partial
      protection. Protective activity was observed with some serum pools that lacked
      detectable complement-mediated bactericidal activity (titers < 1:4) and
      correlated with increasing antibody avidity. Thus, not only does the magnitude of
      the group C antibody response to meningococcal polysaccharide vaccine increase
      with increasing age but there are also age-related affects on antibody functional
      activity such that higher serum concentrations of vaccine-induced antibody are
      required for protection of immunized children than for immunized adults.

PMID- 12496178
TI  - Impact of vector priming on the immunogenicity of recombinant Salmonella
      vaccines.
AB  - There are conflicting reports concerning the impact of prior vector priming on
      the immunogenicity of recombinant-Salmonella-based vaccines. A comparison of
      experimental protocols identified two variables which might account for this
      inconsistency: the potential of the vector strain to colonize the murine gut
      associated lymphoid tissue (GALT) and the nature of the foreign antigen
      subsequently delivered by the recombinant Salmonella construct. The former was
      investigated by constructing an aroA mutant of the Salmonella enterica serovar
      Stanley vector previously used in our laboratory. Although the introduction of an
      aroA mutation had surprisingly little effect on GALT colonization, it did reduce
      the strength of antilipopolysaccharide (anti-LPS) antibody responses and the
      impact of vector priming. Studies were also performed to ascertain the extent to
      which any observed hyporesponsiveness consequent upon vector priming might be
      determined by the characteristics of the foreign antigen. S. enterica serovar
      Stanley was used to deliver either of two Escherichia coli antigens, K88 pilus
      protein or the LT-B toxin subunit, to vector-primed mice. Both serum
      immunoglobulin G (IgG) and intestinal IgA responses to K88 were completely
      abolished, and those to LT-B were significantly reduced, as a consequence of
      vector priming. When similar experiments were performed with an aroA S. enterica
      serovar Dublin vector, responses to K88 were significantly reduced but those to
      LT-B were unaffected by vector priming. Paradoxically, a priming infection with
      this vector induced stronger anti-LPS antibody responses but was less likely to
      elicit a state of hyporesponsiveness to subsequently presented foreign antigen.
      The impact of vector priming thus depends on both the Salmonella strain used and
      the nature of the foreign antigen, but our present data strengthen concerns that
      preexisting antivector immunity represents a serious threat to the Salmonella
      based vaccine strategy.

PMID- 12496179
TI  - luxS and arcB control aerobic growth of Actinobacillus actinomycetemcomitans
      under iron limitation.
AB  - LuxS is responsible for the production of autoinducer 2 (AI-2), which functions
      in Vibrio harveyi as a quorum-sensing signal that controls the cell density
      dependent expression of the lux operon. In nonluminescent organisms, the
      physiologic role of AI-2 is not clear. We report that inactivation of luxS in
      Actinobacillus actinomycetemcomitans JP2 results in reduced growth of the mutant,
      but not the wild-type organism, under aerobic, iron-limited conditions. Stunted
      cultures of the luxS mutant A. actinomycetemcomitans JP2-12 grew to high cell
      density when subcultured under iron-replete conditions. In addition, the mutant
      strain grew to high cell density under iron limitation after transformation with
      a plasmid containing a functional copy of luxS. Results of real-time PCR showed
      that A. actinomycetemcomitans JP2-12 exhibited significantly reduced expression
      of afuA (eightfold), fecBCDE (10-fold), and ftnAB (>50-fold), which encode a
      periplasmic ferric transport protein, a putative ferric citrate transporter, and
      ferritin, respectively. The expressions of putative receptors for transferrin,
      hemoglobin, and hemophore binding protein were also reduced at more modest levels
      (two- to threefold). In contrast, expressions of sidD and frpB (encoding putative
      siderophore receptors) were increased 10- and 3-fold, respectively, in the luxS
      mutant. To better understand the mechanism of the AI-2 response, the A.
      actinomycetemcomitans genome was searched for homologs of the V. harveyi signal
      transduction proteins, LuxP, LuxQ, LuxU, and LuxO. Interestingly, ArcB was found
      to be most similar to LuxQ sensor/kinase. To determine whether arcB plays a role
      in the response of A. actinomycetemcomitans to AI-2, an arcB-deficient mutant was
      constructed. The isogenic arcB mutant grew poorly under anaerobic conditions but
      grew normally under aerobic iron-replete conditions. However, the arcB mutant
      failed to grow aerobically under iron limitation, and reverse transcriptase PCR
      showed that inactivation of arcB resulted in decreased expression of afuA and
      ftnAB. Thus, isogenic luxS and arcB mutants of A. actinomycetemcomitans exhibit
      similar phenotypes when cultured aerobically under iron limitation, and both
      mutants exhibit reduced expression of a common set of genes involved in the
      transport and storage of iron. These results suggest that LuxS and ArcB may act
      in concert to control the adaptation of A. actinomycetemcomitans to iron-limiting
      conditions and its growth under such conditions.

PMID- 12496180
TI  - A GRA1 DNA vaccine primes cytolytic CD8(+) T cells to control acute Toxoplasma
      gondii infection.
AB  - Protective immunity against Toxoplasma gondii is known to be mediated mainly by T
      lymphocytes and gamma interferon (IFN-gamma). The contribution of CD4(+) and
      CD8(+) T-lymphocyte subsets to protective immune responses against T. gondii
      infection, triggered by a GRA1 (p24) DNA vaccine, was assessed in this study. In
      vitro T-cell depletion experiments indicated that both CD4(+) and CD8(+) T-cell
      subsets produced IFN-gamma upon restimulation with a T. gondii lysate. In
      addition, the GRA1 DNA vaccine elicited CD8(+) T cells that were shown to have
      cytolytic activity against parasite-infected target cells and a GRA1-transfected
      cell line. C3H mice immunized with the GRA1 DNA vaccine showed 75 to 100%
      protection, while 0 to 25% of the mice immunized with the empty control vector
      survived challenge with T. gondii cysts. In vivo T-cell depletion experiments
      indicated that CD8(+) T cells were essential for the survival of GRA1-vaccinated
      C3H mice during the acute phase of T. gondii infection, while depletion of CD4(+)
      T cells led to an increase in brain cyst burden during the chronic phase of
      infection.

PMID- 12496181
TI  - Expression of L-Selectin (CD62L), CD44, and CD25 on activated bovine T cells.
AB  - Mycobacterium bovis infection of cattle represents a natural host-pathogen
      interaction and, in addition to its economic and zoonotic impact, represents a
      model for human tuberculosis. Extravasation and trafficking of activated
      lymphocytes to inflammatory sites is modulated by differential expression of
      multiple surface adhesion molecules. However, effects of M. bovis infection on
      adhesion molecule expression have not been characterized. To determine these
      changes, peripheral blood mononuclear cells from M. bovis-infected cattle were
      stimulated with M. bovis purified protein derivative (PPD) or pokeweed mitogen
      (PWM) and evaluated concurrently for proliferation and activation marker
      expression. Stimulation with PPD or PWM increased CD25 and CD44 mean fluorescence
      intensity (MFI) and decreased CD62L MFI on CD4(+) cells from infected animals.
      CD62L MFI on PPD- and PWM-stimulated gammadelta T-cell receptor-positive (TCR(+))
      and CD8(+) cells was also reduced compared to that of nonstimulated gammadelta
      TCR(+) and CD8(+) cells. Using a flow cytometry-based proliferation assay, it was
      determined that proliferating cells, regardless of lymphocyte subset, exhibited
      increased expression of CD25 and CD44 and decreased expression of CD62L compared
      to cells that had not proliferated. In contrast to proliferation, activation
      induced apoptosis of CD4(+) cells resulted in a significant down regulation of
      CD44 expression. Lymphocytes obtained from lungs of M. bovis-infected cattle also
      had reduced expression of CD44 compared to lymphocytes from lungs of noninfected
      cattle. These alterations in surface molecule expression upon activation likely
      impact trafficking to sites of inflammation and the functional capacity of these
      cells within tuberculous granulomas.

PMID- 12496182
TI  - Antiviral activity of shiga toxin requires enzymatic activity and is associated
      with increased permeability of the target cells.
AB  - This study expanded our earlier finding that Shiga toxin type 1 (Stx1) has
      activity against bovine leukemia virus (BLV) (W. A. Ferens and C. J. Hovde,
      Infect. Immun. 68:4462-4469, 2000). The Stx molecular motifs required for
      antiviral activity were identified, and a mechanism of Stx action on virally
      infected cells is suggested. Using inhibition of BLV-dependent spontaneous
      lymphocyte proliferation as a measure of antiviral activity, we showed that Stx2
      had antiviral activity similar to that of Stx1. Enzymatic and antiviral
      activities of three StxA1 chain mutants deficient in enzymatic activity or
      aspects of receptor-mediated cytotoxicity were compared. Using protein synthesis
      inhibition to measure enzymatic activity, the mutant E167D was 300-fold less
      catalytically active than wild-type StxA1, was minimally active in antiviral
      assays, and did not inhibit synthesis of viral proteins. Two StxA1 mutants, A231D
      G234E and StxA(1)1 (enzymatically active but unable to kill cells via the
      classical receptor-mediated route), had undiminished antiviral activity. Although
      binding of radiolabeled StxA1 to bovine blood cells or to free virus was not
      detected, flow cytometric analysis showed that the number of BLV-expressing cells
      were specifically reduced in cultures treated with Stx. These unique and rare
      lymphocytes were highly permeable to 40- and 70-kDa fluorescent dextrans,
      indicating that direct absorption of toxins by virus-expressing cells is a
      potential mechanism of target cell intoxication. These results support the
      hypothesis that Stx-producing Escherichia coli colonization of the
      gastrointestinal tract may benefit ruminant hosts by the ability of Stxs to exert
      antiviral activity.

PMID- 12496183
TI  - Role for recombinant gamma-glutamyltransferase from Treponema denticola in
      glutathione metabolism.
AB  - Volatile sulfur compounds, including hydrogen sulfide (H(2)S), have been
      implicated in the development of periodontal disease. Glutathione is an important
      thiol source for H(2)S production in periodontal pockets. Our recent studies have
      delineated a pathway of glutathione metabolism in Treponema denticola that
      releases H(2)S. In this pathway, gamma-glutamyltransferase (GGT) has been
      proposed to catalyze the first step of glutathione degradation. We have cloned
      the gene of GGT from T. denticola, which contains an open reading frame of 726 bp
      encoding a protein of 241 amino acids. Transformation of this gene into
      Escherichia coli led to the expression of a recombinant protein. After
      purification by chromatography, the recombinant protein showed enzymatic activity
      typical of GGT, catalyzing the degradation of Na-gamma-glutamyl-4-nitroaniline
      (GNA) and the hydrolysis of glutathione, releasing glutamic acid or glutamine and
      cysteinylglycine. L-Cysteine is not a substrate of GGT. Importantly, GNA, when
      added to T. denticola, was able to compete with glutathione and inhibit the
      production of H(2)S, ammonia, and pyruvate. This was accompanied by the
      suppression of hemoxidative and hemolytic activities of the bacteria. Purified
      GGT was inactivated by TLCK (Nalpha-p-tosyl-L-lysine chloromethyl ketone) and
      proteinase K treatment. However, higher enzymatic activity was demonstrated in
      the presence of 2-mercaptoethanol and dithiothreitol. Our further experiments
      showed that the addition of recombinant GGT to Porphyromonas gingivalis, a
      bacterium without significant glutathione-metabolizing capacity, drastically
      increased the utilization of glutathione by the bacterium, producing H(2)S,
      ammonia, and pyruvate. This was again accompanied by enhanced bacterial
      hemoxidative and hemolytic activities. Together, the results suggest an important
      role for GGT in glutathione metabolism in oral bacteria.

PMID- 12496184
TI  - sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in
      Staphylococcus aureus.
AB  - In searching the Staphylococcus aureus genome, we previously identified sarT, a
      homolog of sarA, which encodes a repressor for alpha-hemolysin synthesis.
      Adjacent but transcribed divergently to sarT is sarU, which encodes a 247-residue
      polypeptide, almost twice the length of SarA. Sequence alignment disclosed that
      SarU, like SarS, which is another SarA homolog, could be envisioned as a molecule
      with two halves, with each half being homologous to SarA. SarU, as a member of
      the SarA family proteins, disclosed conservation of basic residues within the
      helix-turn-helix motif and within the beta hairpin loop, two putative DNA binding
      domains within this protein family. The transcription of sarU is increased in a
      sarT mutant. Gel shift and transcriptional fusion studies revealed that SarT can
      bind to the sarU promoter region, probably acting as a repressor for sarU
      transcription. The expression of RNAII and RNAIII of agr is decreased in a sarU
      mutant. As RNAIII expression is up-regulated in a sarT mutant, we hypothesize
      that sarT may down regulate agr RNAIII expression by repressing sarU, a positive
      activator of agr expression. We propose that, in addition to the quorum sensing
      effect of the autoinducing peptide of agr, the sarT-sarU pathway may represent a
      secondary amplification loop whereby the expression of agr (e.g., those found in
      vivo) might repress sarT, leading to increased expression of sarU. Elevated sarU
      expression would result in additional amplification of the original agr signal.

PMID- 12496185
TI  - Differential expression of gamma interferon mRNA induced by attenuated and
      virulent Mycobacterium tuberculosis in guinea pig cells after Mycobacterium bovis
      BCG vaccination.
AB  - To determine whether Mycobacterium bovis BCG vaccination would alter gamma
      interferon (IFN-gamma) mRNA expression in guinea pig cells exposed to
      Mycobacterium tuberculosis, we cloned a cDNA encoding guinea pig IFN-gamma from a
      spleen cell cDNA library. The cDNA is composed of 1,110 bp, with an open reading
      frame encoding a 166-amino-acid protein which shows 56 and 41% amino acid
      sequence homology to human and mouse IFN-gamma, respectively. Spleen or lymph
      node cells from naive and BCG-vaccinated guinea pigs were stimulated with
      purified protein derivative (PPD) or M. tuberculosis H37Ra or H37Rv, and the
      total RNA was subjected to Northern blot analysis with a (32)P-labeled probe
      derived from the cDNA clone. Compared to the IFN-gamma mRNA expression in cells
      of naive animals, that in spleen and lymph node cells exposed to various stimuli
      was enhanced after BCG vaccination. However, there was a significant reduction in
      IFN-gamma mRNA levels when cells were stimulated with a multiplicity of infection
      of greater than 1 virulent M. tuberculosis bacterium per 10 cells. The enhanced
      IFN-gamma mRNA response in BCG-vaccinated animals was associated with an increase
      in the proportions of CD4(+) T cells in the spleens, as determined by
      fluorescence-activated cell sorter analysis. Furthermore, the nonadherent
      population in the spleens enriched either by panning with anti-guinea pig
      immunoglobulin G-coated plates or by purification on nylon wool columns produced
      more IFN-gamma mRNA than whole spleen cells following stimulation with
      concanavalin A or PPD. This indicates that T cells are principally responsible
      for the upregulation of IFN-gamma mRNA expression following BCG vaccination. The
      mechanism by which virulent mycobacteria suppress IFN-gamma mRNA accumulation is
      currently under investigation.

PMID- 12496186
TI  - Selective early production of CCL20, or macrophage inflammatory protein 3alpha,
      by human mast cells in response to Pseudomonas aeruginosa.
AB  - Mast cells are important as sentinel cells in host defense against bacterial
      infection. Much of their effectiveness depends upon recruiting other immune
      cells; however, little is known about the mechanisms of this response. CCL20,
      also known as macrophage inflammatory protein-3alpha (MIP-3alpha), Exodus, and
      LARC, is a chemokine known to be a potent chemoattractant for immature dendritic
      cells and T cells. In this study, we examined the human mast cell production of
      both CCL20 and granulocyte-macrophage colony-stimulating factor (GM-CSF), a
      critical cytokine for innate immune responses in the lung, in response to
      Pseudomonas aeruginosa. Reverse transcription-PCR and Western blot analysis
      demonstrated that the human mast cells (HMC-1) express CCL20 mRNA and are able to
      produce a significant amount (32.4 ng/ml) of CCL20 protein following stimulation
      by calcium ionophore and phorbol myristate acetate. Importantly, P. aeruginosa
      potently stimulated CCL20 production in human cord blood-derived mast cells
      (CBMC), with production peaking at 6 h after stimulation. This time course of
      expression was distinct from that of GM-CSF, which peaked after 24 to 48 h.
      Significant CCL20 production did not occur following immunoglobulin E-mediated
      activation of CBMC under conditions which induced a substantial GM-CSF response.
      Interestingly, the CCL20 response of mast cells to P. aeruginosa was relatively
      resistant to inhibition by the corticosteroid dexamethasone, interleukin-10, or
      cyclosporine, while GM-CSF production was potently inhibited. However, P.
      aeruginosa-induced CCL20 production was blocked by the protein kinase C (PKC)
      inhibitor Ro 31-8220 and a PKC pseudosubstrate. These results support a role for
      human mast cells in the initiation of immune responses to P. aeruginosa
      infection.

PMID- 12496187
TI  - Effective protective immunity to Yersinia pestis infection conferred by DNA
      vaccine coding for derivatives of the F1 capsular antigen.
AB  - Three plasmids expressing derivatives of the Yersinia pestis capsular F1 antigen
      were evaluated for their potential as DNA vaccines. These included plasmids
      expressing the full-length F1, F1 devoid of its putative signal peptide (deF1),
      and F1 fused to the signal-bearing E3 polypeptide of Semliki Forest virus
      (E3/F1). Expression of these derivatives in transfected HEK293 cells revealed
      that deF1 is expressed in the cytosol, E3/F1 is targeted to the secretory
      cisternae, and the nonmodified F1 is rapidly eliminated from the cell.
      Intramuscular vaccination of mice with these plasmids revealed that the vector
      expressing deF1 was the most effective in eliciting anti-F1 antibodies. This
      response was not limited to specific mouse strains or to the mode of DNA
      administration, though gene gun-mediated vaccination was by far more effective
      than intramuscular needle injection. Vaccination of mice with deF1 DNA conferred
      protection against subcutaneous infection with the virulent Y. pestis Kimberley53
      strain, even at challenge amounts as high as 4,000 50% lethal doses. Antibodies
      appear to play a major role in mediating this protection, as demonstrated by
      passive transfer of anti-deF1 DNA antiserum. Taken together, these observations
      indicate that a tailored genetic vaccine based on a bacterial protein can be used
      to confer protection against plague in mice without resorting to regimens
      involving the use of purified proteins.

PMID- 12496188
TI  - Interaction of Ler at the LEE5 (tir) operon of enteropathogenic Escherichia coli.
AB  - The genome of enteropathogenic Escherichia coli (EPEC) encodes a global
      regulator, Ler (locus of enterocyte effacement [LEE]-encoded regulator), which
      activates expression of several polycistronic operons within the 35.6-kb LEE
      pathogenicity island, including the LEE2-LEE3 divergent operon pair containing
      overlapping -10 regions and the LEE5 (tir) operon. Ler is a predicted 15-kDa
      protein that exhibits amino acid similarity with the nucleoid protein H-NS. In
      order to study Ler-mediated activation of virulence operons in EPEC, we used a
      molecular approach to characterize the interactions of purified Ler protein with
      the upstream regulatory sequences of the LEE5 operon. We determined the cis
      acting DNA sequences necessary for Ler binding at LEE5 by mobility shift and
      DNase I protection assays, demonstrating that Ler acts directly at LEE5 by
      binding sequences between positions -190 and -73 in relation to the
      transcriptional start site. Based on the molecular weight of Ler, the similarity
      to H-NS, and the extended region of protection observed in a DNase I footprint at
      LEE5, we hypothesized that multiple Ler proteins bind upstream of the LEE5
      promoter to increase transcriptional activity from a distance. Using an hns
      deletion strain, we demonstrated that like the LEE2-LEE3 operon pair, H-NS
      represses LEE5 transcription. We describe a model in which Ler activates
      transcription at both divergent overlapping paired and single promoters by
      displacing H-NS, which results in the disruption of a repressing nucleoprotein
      complex.

PMID- 12496189
TI  - CD36-mediated nonopsonic phagocytosis of erythrocytes infected with stage I and
      IIA gametocytes of Plasmodium falciparum.
AB  - Gametocytes, the sexual stages of malaria parasites (Plasmodium spp.) that are
      transmissible to mosquitoes, have been the focus of much recent research as
      potential targets for novel drug and vaccine therapies. However, little is known
      about the host clearance of gametocyte-infected erythrocytes (GEs). Using a
      number of experimental strategies, we found that the scavenger receptor CD36
      mediates the uptake of nonopsonized erythrocytes infected with stage I and IIA
      gametocytes of Plasmodium falciparum by monocytes and culture-derived macrophages
      (Mphis). Light microscopy and immunofluorescence assays revealed that stage I and
      IIA gametocytes were readily internalized by monocytes and Mphis. Pretreating
      monocytes and Mphis with a monoclonal antibody that blocked CD36 resulted in a
      significant reduction in phagocytosis, as did treating GEs with low
      concentrations of trypsin to remove P. falciparum erythrocyte membrane protein 1
      (PfEMP-1), a parasite ligand for CD36. Pretreating monocytes and Mphis with
      peroxisome proliferator-activated receptor gamma-retinoid X receptor agonists,
      which specifically upregulate CD36, resulted in a significant increase in the
      phagocytosis of GEs. Murine CD36 on mouse Mphis also mediated the phagocytosis of
      P. falciparum stage I and IIA gametocytes, as determined by receptor blockade
      with anti-murine CD36 monoclonal antibodies and the lack of uptake by CD36-null
      Mphis. These results indicate that phagocytosis of stage I and IIA gametocytes by
      monocytes and Mphis appears to be mediated to a large extent by the interaction
      of PfEMP-1 and CD36, suggesting that CD36 may play a role in innate clearance of
      these early sexual stages.

PMID- 12496190
TI  - Intradermal infection model for pathogenesis and vaccine studies of murine
      visceral leishmaniasis.
AB  - The levels of protection found in vaccine studies of murine visceral
      leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether
      this is due to the high-challenge murine model employed and/or is a consequence
      of differences required in tissue-specific local immune responses is not
      understood. Consequently, an intradermal murine model of visceral leishmaniasis
      has been explored. Intradermal inoculation established a chronic infection in
      susceptible mice which was associated with a pattern of parasite clearance with
      time postinfection in the liver and skin; in contrast, parasite persistence and
      expansion was observed in lymphoid tissue (spleen and draining lymph node). The
      course of disease found appears to be similar to those reported for subclinical
      canine and human visceral leishmaniasis. Clearance of parasites from the skin was
      correlated with an inflammatory response and the infiltration and activation of
      CD4(+) and CD8(+) T cells. In contrast, in lymphoid tissue (lymph node or
      spleen), the production of Th1/Th2 cytokines (interleukin-4 [IL-4], IL-10, and
      gamma interferon) appeared to correlate with parasite burden and pathogenesis. In
      vaccination experiments employing the Leishmania infantum D-13 (p80) antigen,
      significantly higher levels of protection were found with the intradermal murine
      model (29 to 7,500-fold more than naive controls) than were found with a low-dose
      intravenous infection model (9 to 173-fold). Thus, this model should prove useful
      for further investigation of disease pathogenesis as well as vaccine studies of
      visceral leishmaniasis.

PMID- 12496191
TI  - Roles of the Maltese cross form in the development of parasitemia and protection
      against Babesia microti infection in mice.
AB  - Babesia microti, a hemoprotozoan parasite of rodents, is also important as a
      zoonotic agent of human babesiosis. The Maltese cross form, which consists of
      four masses in an erythrocyte, is characteristic of the developmental stage of B.
      microti. Monoclonal antibody (MAb) 2-1E, which specifically recognizes the
      Maltese cross form of B. microti, has been described previously. In the present
      study, we examined the roles of the Maltese cross form during the infectious
      course of B. microti in mice. The number of the Maltese cross form increased in
      the peripheral blood of infected mice prior to the peak of parasitemia. With
      confocal laser scanning microscopy, MAb 2-1E was found to be reactive with the
      ring form, with the parasites undergoing transformation to the Maltese cross form
      and subsequent division, and also with extracellular merozoites. Furthermore, the
      Maltese cross form-related antigen (MRA) gene was isolated from a B. microti cDNA
      library by immunoscreening with MAb 2-1E, and the nucleotide sequence was
      determined. Genomic analyses indicated that the MRA gene exists as a single-copy
      gene in B. microti. Immunization of mice with recombinant MRA induced significant
      protective immunity against B. microti infection. These findings indicate that
      the Maltese cross form plays important roles in both the development of
      parasitemia and the protective response against the infection.

PMID- 12496192
TI  - The Salmonella enterica serovar typhimurium translocated effectors SseJ and SifB
      are targeted to the Salmonella-containing vacuole.
AB  - The Salmonella enterica serovar Typhimurium type III secretion system (TTSS)
      encoded in Salmonella pathogenicity island 2 (SPI-2) promotes replication within
      host cells and systemic infection of mice. The SPI-2 TTSS is expressed following
      Salmonella internalization into host cells and translocates effectors across the
      membrane of the Salmonella-containing vacuole (SCV). Two effectors with similar
      amino-terminal domains, SseJ and SifB, localize to the SCV membrane in infected
      HEp-2 cells and subsequently traffic away from the SCV along Salmonella-induced
      filaments (Sifs). Following infection of RAW cells, SseJ and SifB localize to the
      SCV as well as LAMP-1-positive, vesicular-appearing structures distant from the
      SCV. Trafficking of SseJ and SifB away from the SCV requires the SPI-2 effector
      SifA. Deletion of sseJ, but not sifB, leads to attenuation of Salmonella
      replication in mice following intraperitoneal inoculation. The contribution of
      SseJ to in vivo replication is identical in wild-type and sifA deletion
      backgrounds, suggesting that SseJ trafficking away from the SCV along Sifs is
      unnecessary for its virulence function.

PMID- 12496193
TI  - Divergent patterns of colonization and immune response elicited from two
      intestinal Lactobacillus strains that display similar properties in vitro.
AB  - Lactobacilli derived from the endogenous flora of normal donors are being
      increasingly used as probiotics in functional foods and as vaccine carriers.
      However, a variety of studies done with distinct strains of lactobacilli has
      suggested heterogeneous and strain-specific effects. To dissect this
      heterogeneity at the immunological level, we selected two strains of lactobacilli
      that displayed similar properties in vitro and studied their impact on mucosal
      and systemic B-cell responses in monoxenic mice. Germfree mice were colonized
      with Lactobacillus johnsonii (NCC 533) or Lactobacillus paracasei (NCC 2461).
      Bacterial loads were monitored for 30 days in intestinal tissues, and mucosal and
      systemic B-cell responses were measured. Although both Lactobacillus strains
      displayed similar growth, survival, and adherence properties in vitro, they
      colonized the intestinal lumen and translocated into mucosal lymphoid organs at
      different densities. L. johnsonii colonized the intestine very efficiently at
      high levels, whereas the number of L. paracasei decreased rapidly and it
      colonized at low levels. We determined whether this difference in colonization
      correlated with an induction of different types of immune responses. We observed
      that colonization with either strain induced similar germinal center formation
      and immunoglobulin A-bearing lymphocytes in the mucosa, suggesting that both
      strains were able to activate mucosal B-cell responses. However, clear
      differences in patterns of immunoglobulins were observed between the two strains
      in the mucosa and in the periphery. Therefore, despite similar in vitro probiotic
      properties, distinct Lactobacillus strains may colonize the gut differently and
      generate divergent immune responses.

PMID- 12496194
TI  - Normal host defense during systemic candidiasis in mannose receptor-deficient
      mice.
AB  - Pathogen pattern recognition receptors (PRRs) recognize common structural and
      molecular motifs present on microbial surfaces and contribute to induction of
      innate immune responses. The mannose receptor (MR), a carbohydrate-binding
      receptor expressed on subsets of macrophages, is considered one such PRR. In
      vitro experiments have implicated the MR in phagocytosis of mannose-bearing
      microbes, including Candida albicans, and enhancement of antifungal response by
      macrophages. However, the significance of the MR's contribution to immune
      response during systemic C. albicans infection has never been directly
      demonstrated. Using MR-deficient mice in an in vivo infection experiment, we
      examined the role of the MR in immune response during disseminated candidiasis.
      MR(-/-) and wild-type control mice were challenged intraperitoneally with C.
      albicans, and the survival rates, tissue fungal burden, inflammatory cell
      recruitment, and specific antibody production after infection were evaluated. We
      found no significant difference in survival between the two mouse strains. MR(-/
      ) mice had higher average fungal burdens in some of the organs on days 7 and 21
      but exhibited competence in inflammatory cell recruitment and antibody
      production. We also observed in vitro that MR(-/-) peritoneal cavity macrophages
      were equally capable of C. albicans uptake and that phagocytosis could be blocked
      with beta-glucan. We conclude that the MR is not required for the normal host
      defense during disseminated candidiasis or for the phagocytosis of C. albicans
      and that a beta-glucan receptor may be required for C. albicans phagocytosis.

PMID- 12496195
TI  - Cytotoxic effects of streptolysin o and streptolysin s enhance the virulence of
      poorly encapsulated group a streptococci.
AB  - Although the toxicity of streptolysin O (SLO) and streptolysin S (SLS) in
      purified group A streptococci (GAS) has been established, the effect of these
      molecules in natural infection is not well understood. To identify whether
      biologically relevant concentrations of SLO and SLS were cytotoxic to epithelial
      and phagocytic cells that the bacteria would typically encounter during human
      infection and to characterize the influence of cell injury on bacterial
      pathogenesis, we derived GAS strains deficient in SLO or SLS in the background of
      an invasive GAS M3 isolate and determined their virulence in in vitro and in vivo
      models of human disease. Whereas bacterial production of SLO resulted in lysis of
      both human keratinocytes and polymorphonuclear leukocytes, GAS expression of SLS
      was associated only with keratinocyte injury. Expression of SLO but not SLS
      impaired polymorphonuclear leukocyte killing of GAS in vitro, but this effect
      could only be demonstrated in the background of acapsular organisms. In mouse
      invasive soft-tissue infection, neither SLO or SLS expression significantly
      influenced mouse survival. By contrast, in a mouse model of bacterial sepsis
      after intraperitoneal inoculation of GAS, SLO expression enhanced the virulence
      of both encapsulated and acapsular GAS, whereas SLS expression increased the
      virulence only of acapsular GAS. We conclude that the cytotoxic effects of SLO
      protect GAS from phagocytic killing and enhance bacterial virulence, particularly
      of strains that may be relatively deficient in hyaluronic acid capsule. Compared
      to SLO, SLS in this strain background has a more modest influence on GAS
      pathogenicity and the effect does not appear to involve bacterial resistance to
      phagocytosis.

PMID- 12496196
TI  - Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel
      antibiotic strategy against tuberculosis: demonstration of efficacy in vivo.
AB  - Tuberculosis remains one of humankind's greatest killers, and new therapeutic
      strategies are needed to combat the causative agent, Mycobacterium tuberculosis,
      which is rapidly developing resistance to conventional antibiotics. Using the
      highly demanding guinea pig model of pulmonary tuberculosis, we have investigated
      the feasibility of inhibiting M. tuberculosis glutamine synthetase (GS), an
      enzyme that plays a key role in both nitrogen metabolism and cell wall
      biosynthesis, as a novel antibiotic strategy. In guinea pigs challenged by
      aerosol with the highly virulent Erdman strain of M. tuberculosis, the GS
      inhibitor L-methionine-SR-sulfoximine (MSO) protected the animals against weight
      loss, a hallmark of tuberculosis, and against the growth of M. tuberculosis in
      the lungs and spleen; MSO reduced the CFU of M. tuberculosis at 10 weeks after
      challenge by approximately 0.7 log unit compared with that in control animals.
      MSO acted synergistically with isoniazid in protecting animals against weight
      loss and bacterial growth, reducing the CFU in the lungs and spleen by
      approximately 1.5 log units below the level seen with isoniazid alone. In the
      presence of ascorbate, which allows treatment with a higher dose, MSO was highly
      efficacious, reducing the CFU in the lungs and spleen by 2.5 log units compared
      with that in control animals. This study demonstrates that inhibition of M.
      tuberculosis GS is a feasible therapeutic strategy against this pathogen and
      supports the concept that M. tuberculosis enzymes involved in cell wall
      biosynthesis, including major secretory proteins, have potential as antibiotic
      targets.

PMID- 12496197
TI  - Differential cytokine pattern in the spleens and livers of BALB/c mice infected
      with Penicillium marneffei: protective role of gamma interferon.
AB  - Penicillium marneffei is an intracellular opportunistic fungus causing invasive
      mycosis in AIDS patients. T cells and macrophages are important for protection in
      vivo. However, the role of T-cell cytokines in the immune response against P.
      marneffei is still unknown. We studied by semiquantitative reverse transcription
      PCR and biological assays the patterns of expression of Th1 and Th2 cytokines in
      the organs of wild-type (wt) and gamma interferon (IFN-gamma) knockout (GKO) mice
      infected intravenously with P. marneffei conidia. At 3 x 10(5) conidia/mouse, a
      self-limiting infection developed in wt BALB/c mice, whereas all GKO mice died at
      day 18 postinoculation. Splenic and hepatic granulomas were present in wt mice,
      whereas disorganized masses of macrophages and yeast cells were detected in GKO
      mice. The infection resolved faster in the spleens than in the livers of wt mice
      and was associated with the local expression of type 1 cytokines (high levels of
      interleukin-12 [IL-12] and IFN-gamma) but not type 2 cytokines (low levels of IL
      4 and IL-10). Conversely, both type 1 and type 2 cytokines were detected in the
      livers of wt animals. Disregulation of the cytokine profile was seen in the
      spleens but not in the livers of GKO mice. The inducible nitric oxide synthase
      mRNA level was low and the TNF-alpha level was high in both spleens and livers of
      GKO mice compared to wt mice. These data suggest that the polarization of a
      protective type 1 immune response against P. marneffei is regulated at the level
      of individual organs and that the absence of IFN-gamma is crucial for the
      activation of fungicidal macrophages and the development of granulomas.

PMID- 12496198
TI  - Identification of LpeA, a PsaA-like membrane protein that promotes cell entry by
      Listeria monocytogenes.
AB  - The intracellular life of Listeria monocytogenes starts by a complex process of
      entry involving several bacterial ligands and eukaryotic receptors. In this work,
      we identified in silico from the sequence of the genome of L. monocytogenes a
      previously unknown gene designated lpeA (for lipoprotein promoting entry)
      encoding a 35-kDa protein homologous to PsaA, a lipoprotein belonging to the LraI
      family and implicated in the cell adherence of Streptococcus pneumoniae and
      related species. By constructing a mutant of L. monocytogenes in which lpeA is
      deleted (lpeA mutant), we show that the PsaA-like protein LpeA is not involved in
      bacterial adherence but is required for entry of L. monocytogenes in eukaryotic
      cells. In contrast to wild-type bacteria, mutant bacteria failed to invade the
      epithelial Caco-2 and hepatocyte TIB73 cell lines, as confirmed by confocal
      microscopy. The mutant bacteria rapidly penetrated in mouse bone marrow-derived
      macrophages. Surprisingly, lpeA mutant bacteria survive better in macrophages
      than do wild-type bacteria. This was correlated with a weak exacerbation of
      virulence of the lpeA mutant in the mouse. LpeA is therefore a novel invasin
      favoring the entry of L. monocytogenes into nonprofessional phagocytes but not
      its invasion of macrophages. This is the first report of a lipoprotein promoting
      cell invasion of an intracellular pathogen.

PMID- 12496199
TI  - Mapping of murine Th1 helper T-Cell epitopes of mycolyl transferases Ag85A,
      Ag85B, and Ag85C from Mycobacterium tuberculosis.
AB  - BALB/c (H-2(d)) and C57BL/6 (H-2(b)) mice were infected intravenously with
      Mycobacterium tuberculosis H37Rv or vaccinated intramuscularly with plasmid DNA
      encoding each of the three mycolyl transferases Ag85A, Ag85B, and Ag85C from M.
      tuberculosis. Th1-type spleen cell cytokine secretion of interleukin-2 (IL-2) and
      gamma interferon (IFN-gamma) was analyzed in response to purified Ag85 components
      and synthetic overlapping peptides covering the three mature sequences.
      Tuberculosis-infected C57BL/6 mice reacted strongly to some peptides from Ag85A
      and Ag85B but not from Ag85C, whereas tuberculosis-infected BALB/c mice reacted
      only to peptides from Ag85A. In contrast, spleen cells from both mouse strains
      produced elevated levels of IL-2 and IFN-gamma following vaccination with Ag85A,
      Ag85B, and Ag85C DNA in response to peptides of the three Ag85 proteins, and the
      epitope repertoire was broader than in infected mice. Despite pronounced sequence
      homology, a number of immunodominant regions contained component specific
      epitopes. Thus, BALB/c mice vaccinated with all three Ag85 genes reacted against
      the same amino acid region, 101 to 120, that was also immunodominant for Ag85A in
      M. bovis BCG-vaccinated and tuberculosis-infected H-2(d) haplotype mice, but
      responses were completely component specific. In C57BL/6 mice, a cross-reactive T
      cell response was detected against two carboxy-terminal peptides spanning amino
      acids 241 to 260 and 261 to 280 of Ag85A and Ag85B. These regions were not
      recognized at all in C57BL/6 mice vaccinated with Ag85C DNA. Our results
      underline the need for comparative analysis of all three Ag85 components in
      future vaccination studies.

PMID- 12496200
TI  - Role of avian pathogenic Escherichia coli virulence factors in bacterial
      interaction with chicken heterophils and macrophages.
AB  - Avian pathogenic Escherichia coli (APEC) cause extraintestinal disease in avian
      species via respiratory tract infection. Virulence factors associated with APEC
      include type 1 and P fimbriae, curli, aerobactin, lipopolysaccharide (LPS), K1
      capsular antigen, temperature-sensitive hemagglutinin (Tsh), and an
      uncharacterized pathogen-specific chromosomal region (the 0-min region). The role
      of these virulence factors in bacterial interaction with phagocytes was
      investigated by using mutants of three APEC strains, each belonging to one of the
      most predominant serogroups O1, O2, and O78. Bacterial cell interaction with
      avian phagocytes was tested with primary cultures of chicken heterophils and
      macrophages. The presence of type 1 fimbriae and, in contrast, the absence of P
      fimbriae, K1 capsule, O78 antigen, and the 0-min region promoted bacterial
      association with chicken heterophils and macrophages. The presence of type 1 and
      P fimbriae, O78 antigen, and the 0-min region seemed to protect bacteria against
      the bactericidal effect of phagocytes, especially heterophils. The tested
      virulence factors seemed to have a limited role in intracellular survival for up
      to 48 h in macrophages. Generally, opsonized and nonopsonized bacteria were
      eliminated to the same extent, but in some cases, unopsonized bacteria were
      eliminated to a greater extent than opsonized bacteria. These results confirm the
      important role of type 1 fimbriae in promotion of initial phagocytosis, but
      nevertheless indicate a role for type 1 fimbriae in the protection of bacteria
      from subsequent killing, at least in heterophils. The results also indicate a
      role for K1 capsule, O78 antigen, P fimbriae, and the 0-min region in initial
      avoidance of phagocytosis, but demonstrate an additional role for O78 antigen, P
      fimbriae, and the 0-min region in subsequent protection against the bactericidal
      effects of phagocytes after bacterial association has occurred.

PMID- 12496201
TI  - Cholera toxin induces migration of dendritic cells from the subepithelial dome
      region to T- and B-cell areas of Peyer's patches.
AB  - Intestinal M cells deliver macromolecules, particles, and pathogens into the
      subepithelial dome (SED) region of Peyer's patch mucosa, an area rich in
      dendritic cells (DCs). We tested whether uptake of the mucosal adjuvant cholera
      toxin (CT) or live Salmonella bacteria can induce DC migration within Peyer's
      patches. Virus-sized, fluorescent polystyrene microparticles were efficiently
      transported by M cells and ingested by CD11c(+), CD11b(-), and CD8a(-) DCs in the
      SED region. DCs loaded with microparticles remained in the SED for up to 14 days.
      CT (but not the CT B subunit) and live attenuated Salmonella enterica serovar
      Typhimurium bacteria induced migration of the microparticle-loaded DCs from the
      SED region into underlying B-cell follicles and adjacent parafollicular T-cell
      zones. Our data provide the first demonstration that DCs move in response to
      enterotoxin adjuvants and live bacteria that enter the mucosa via M cells.

PMID- 12496202
TI  - The vibrio pathogenicity island-encoded mop protein modulates the pathogenesis
      and reactogenicity of epidemic vibrio cholerae.
AB  - Epidemic Vibrio cholerae possess the VPI (Vibrio pathogenicity island) essential
      virulence gene cluster. The VPI is 41.2 kb in size and encodes 29 potential
      proteins, several of which have no known function. We show that the VPI-encoded
      Orf4 is a predicted 34-kDa periplasmic protein containing a zinc metalloprotease
      motif. V. cholerae seventh-pandemic (El Tor) strain N16961 carrying an orf4
      mutation showed no obvious difference relative to its parent in the production of
      cholera toxin and the toxin-coregulated pilus, motility, azocasein digestion, and
      colonization of infant mice. However, analysis of rabbit ileal loops revealed
      that the N16961 orf4 mutant is hypervirulent, causing increased serosal
      hemorrhage and reactogenicity compared to its parent. Histology revealed a
      widening of submucosa, with an increase in inflammatory cells, diffuse lymphatic
      vessel dilatation, edema, endothelial cell hypertrophy of blood vessels, blunting
      of villi, and lacteal dilatation with lymphocytes and polymorphonuclear
      leukocytes. The mutant could be complemented in vivo with an orf4 gene on a
      plasmid but not with an orf4 gene containing a site-directed mutation in the
      putative zinc metalloprotease motif. Although its mechanism of its action is
      being studied further, our results suggest that the Orf4 protein is a zinc
      metalloprotease that modulates the pathogenesis and reactogenicity of epidemic V.
      cholerae. Based on our findings, we name this VPI-encoded protein Mop (for
      modulation of pathogenesis).

PMID- 12496203
TI  - Role of sarA in the pathogenesis of Staphylococcus aureus musculoskeletal
      infection.
AB  - We recently demonstrated that mutation of sarA in clinical isolates of
      Staphylococcus aureus results in a phenotype that is distinct by comparison to
      sarA mutants generated in the laboratory strain RN6390 (J. S. Blevins, K. E.
      Beenken, M. O. Elasri, B. K. Hurlburt, and M. S. Smeltzer, Infect. Immun. 70:470
      480, 2002). This raises the possibility that studies demonstrating that RN6390
      sarA mutants are attenuated do not accurately reflect the role of sarA in the
      pathogenesis of staphylococcal disease. To test this hypothesis, we used a murine
      model of musculoskeletal infection to assess the virulence of sarA and agr
      mutants generated in a clinical isolate of S. aureus (UAMS-1). By using this
      model, we confirmed that mutation of sarA and/or agr results in a reduced
      capacity to cause both septic arthritis and osteomyelitis.

PMID- 12496204
TI  - Production of macrophage inflammatory protein 3alpha (MIP-3alpha) (CCL20) and MIP
      3beta (CCL19) by human peripheral blood neutrophils in response to microbial
      pathogens.
AB  - Effects of bacterial pathogens on the production of macrophage inflammatory
      protein 3alpha (MIP-3alpha) and MIP-3beta from human peripheral blood neutrophils
      were investigated. Neutrophils produced both chemokines by coincubation with
      either gram-positive or gram-negative bacteria. Neutrophils may initiate antigen
      specific immune responses through the release of these chemokines that are
      capable of promoting selective recruitment of dendritic cells and T-cell subsets.

PMID- 12496205
TI  - Expression of proinflammatory cytokines and receptors by human fallopian tubes in
      organ culture following challenge with Neisseria gonorrhoeae.
AB  - Infection of the Fallopian tubes (FT) by Neisseria gonorrhoeae can lead to acute
      salpingitis, an inflammatory condition, which is a major cause of infertility.
      Challenge of explants of human FT with gonococci induced mRNA expression and
      protein secretion for the proinflammatory cytokines interleukin (IL)-1alpha, IL
      1beta, and tumor necrosis factor alpha (TNF-alpha) but not for granulocyte
      macrophage colony-stimulating factor. In contrast, FT expression of IL-6 and of
      the cytokine receptors IL-6R, TNF receptor I (TNF-RI), and TNF-RII was
      constitutive and was not increased by gonococcal challenge. These studies suggest
      that several proinflammatory cytokines are likely to contribute to the cell and
      tissue damage observed in gonococcal salpingitis.

PMID- 12496206
TI  - Vibrio vulnificus induces macrophage apoptosis in vitro and in vivo.
AB  - In this study, we compared the apoptotic activities of clinical and environmental
      isolates of Vibrio vulnificus toward macrophages in vitro and in vivo. The
      clinical isolates induced apoptosis in macrophage-like cells in vitro and in
      macrophages in vivo. This suggests that macrophage apoptosis may be important for
      the clinical virulence of V. vulnificus.

PMID- 12496207
TI  - Role of virulence factors in resistance of avian pathogenic Escherichia coli to
      serum and in pathogenicity.
AB  - In chickens, colibacillosis is caused by avian pathogenic Escherichia coli (APEC)
      via respiratory tract infection. Many virulence factors, including type 1 (F1A)
      and P (F11) fimbriae, curli, aerobactin, K1 capsule, and temperature-sensitive
      hemagglutinin (Tsh) and plasmid DNA regions have been associated with APEC. A
      strong correlation between serum resistance and virulence has been demonstrated,
      but roles of virulence factors in serum resistance have not been well elucidated.
      By using mutants of APEC strains TK3, MT78, and chi7122, which belong to
      serogroups O1, O2, and O78, respectively, we investigated the role of virulence
      factors in resistance to serum and pathogenicity in chickens. Our results showed
      that serum resistance is one of the pathogenicity mechanisms of APEC strains.
      Virulence factors that increased bacterial resistance to serum and colonization
      of internal organs of infected chickens were O78 lipopolysaccharide of E. coli
      chi7122 and the K1 capsule of E. coli MT78. In contrast, curli, type 1, and P
      fimbriae did not appear to contribute to serum resistance. We also showed that
      the iss gene, which was previously demonstrated to increase resistance to serum
      in certain E. coli strains, is located on plasmid pAPEC-1 of E. coli chi7122 but
      does not play a major role in resistance to serum for strain chi7122.

PMID- 12496208
TI  - Campylobacter jejuni cytolethal distending toxin promotes DNA repair responses in
      normal human cells.
AB  - Cytolethal distending toxin (CDT) is a multisubunit protein found in various gram
      negative bacterial pathogens of humans which is thought to cause cell death by
      direct DNA damage of host cells. We sought to determine if a cellular response to
      DNA damage could be detected by exogenous addition of the holotoxin. Exogenous
      addition of the Campylobacter jejuni 81-176 CDT to primary human fibroblasts
      resulted in formation of Rad50 foci, which are formed around double-stranded-DNA
      breaks. Moreover, such foci are formed in both proliferating and nonproliferating
      cells that are treated with C. jejuni CDT. Fibroblasts that were intoxicated and
      later stimulated to proliferate failed to divide and remained arrested in the
      G(1) phase of the cell cycle.

PMID- 12496209
TI  - MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads to
      protection against oxygen-independent neutrophil killing.
AB  - Staphylococcus aureus achieves resistance to defensins and similar cationic
      antimicrobial peptides (CAMPs) by modifying anionic membrane lipids via MprF with
      L-lysine, which leads to repulsion of these host defense molecules. S. aureus
      DeltamprF, which lacks the modification, was very efficiently killed by
      neutrophil defensins and CAMP-producing leukocytes, even when oxygen-dependent
      killing was disrupted, but was as susceptible as wild-type bacteria to
      inactivation by myeloperoxidase or human monocytes lacking defensins. These
      results demonstrate the impact and specificity of MprF-mediated CAMP resistance
      and underscore the role of defensin-like peptides in innate host defense.

PMID- 12496211
TI  - Involvement of Trypanosoma cruzi metacyclic trypomastigote surface molecule gp82
      in adhesion to gastric mucin and invasion of epithelial cells.
AB  - Upon oral infection, Trypanosoma cruzi metacyclic trypomastigotes invade and
      replicate in the gastric mucosal epithelium, being apparently uniquely
      specialized for adhesion to mucin and mucosal invasion. Here we investigated the
      involvement of gp82, the metacyclic-stage-specific surface glycoprotein
      implicated in host cell entry, in both adhesion to gastric mucin and invasion of
      the mucosal epithelium upon oral challenge. Metacyclic forms, preincubated with a
      control monoclonal antibody (MAb) or with MAb 3F6 directed to gp82, were
      administered orally to BALB/c mice, and parasitemia was monitored. Mice that
      received parasites treated with MAb 3F6 had greatly reduced parasitemia,
      displaying at the peak a mean number of blood parasites more than 100-fold lower
      than that of the control group. MAbs directed to other T. cruzi surface
      glycoproteins had no such effect. gp82, as either a native or a recombinant
      molecule, but not the metacyclic trypomastigote surface molecule gp90 or gp35/50,
      bound to gastric mucin in enzyme-linked immunosorbent assays. MAb 3F6
      significantly inhibited the penetration of cultured epithelial HeLa cells by
      metacyclic forms in the absence or in the presence of gastric mucin. Mucin alone
      did not affect parasite internalization. Parasite infectivity was not altered by
      treatment of metacyclic forms with pepsin, to which gp82 was resistant, or with
      proteinase K, which removed the N-terminal portion of gp82 but preserved its host
      cell binding site. Taken together, these findings suggest that gp82 mediates the
      interaction of metacyclic trypomastigotes with gastric mucin and the subsequent
      penetration of underlying epithelial cells.

PMID- 12496210
TI  - OxyR acts as a repressor of catalase expression in Neisseria gonorrhoeae.
AB  - It has been reported that Neisseria gonorrhoeae possesses a very high level of
      catalase activity, but the regulation of catalase expression has not been
      investigated extensively. In Escherichia coli and Salmonella enterica serovar
      Typhimurium, it has been demonstrated that OxyR is a positive regulator of
      hydrogen peroxide-inducible genes, including the gene encoding catalase. The oxyR
      gene from N. gonorrhoeae was cloned and used to complement an E. coli oxyR
      mutant, confirming its identity and function. The gene was inactivated by
      inserting a kanamycin resistance cassette and used to make a knockout allele on
      the chromosome of N. gonorrhoeae strain 1291. In contrast to E. coli, the N.
      gonorrhoeae oxyR::kan mutant expressed ninefold-more catalase activity and was
      more resistant to hydrogen peroxide killing than the wild type. These data are
      consistent with OxyR in N. gonorrhoeae acting as a repressor of catalase
      expression.

PMID- 12496212
TI  - Feasibility of an HA2 domain-based periodontitis vaccine.
AB  - In a rat periodontitis model, preinoculation with the Porphyromonas gingivalis
      HA2 binding domain for hemoglobin provided protection from disease. Protection
      was associated with induced anti-HA2 immunoglobulin G (IgG) humoral antibodies.
      The IgG subclass ratios suggested that relatively lower Th2/Th1-driven responses
      were directly associated with protection when rHA2 was administered in saline.

PMID- 12496213
TI  - Induction of emetic response to staphylococcal enterotoxins in the house musk
      shrew (Suncus murinus).
AB  - The emetic responses induced by staphylococcal enterotoxin A (SEA), SEB, SEC2,
      SED, SEE, SEG, SEH, and SEI in the house musk shrew (Suncus murinus) were
      investigated. SEA, SEE, and SEI showed higher emetic activity in the house musk
      shrew than the other SEs. SEB, SEC2, SED, SEG, and SEH also induced emetic
      responses in this animal model but relatively high doses were required. The house
      musk shrew appears to be a valuable model for studying the mechanisms of emetic
      reactions caused by SEs.

PMID- 12496214
TI  - A single-copy gene encodes Kex1, a serine endoprotease of Pneumocystis jiroveci.
AB  - We have cloned and characterized the kex1 gene of Pneumocystis jiroveci. Unlike
      the case for Pneumocystis carinii, in which the homologous PRT-1 genes are
      multicopy, kex1 is a single-copy gene encoding a protein homologous to fungal
      serine endoproteases, which localize to the Golgi apparatus. Thus, substantial
      biological differences can be seen among Pneumocystis species.

PMID- 12496215
TI  - Enhanced immunogenicity to Mycobacterium tuberculosis by vaccination with an
      alphavirus plasmid replicon expressing antigen 85A.
AB  - The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA
      replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from
      Mycobacterium tuberculosis was compared with a conventional plasmid DNA vector
      encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long
      term protection against M. tuberculosis compared with the conventional vector.

PMID- 12496216
TI  - Association of Helicobacter pylori antioxidant activities with host colonization
      proficiency.
AB  - To assess the importance of two separate antioxidant activities in Helicobacter
      pylori, we tested the abilities of strains with mutations in either tpx (encoding
      thiolperoxidase) or ahpC (encoding alkyl hydroperoxide reductase [AhpC]) to
      colonize the stomachs of mice. The tpx strain was clearly more sensitive than the
      parent strain to both oxygen and cumene hydroperoxide. The strain colonized only
      5% of the inoculated mice. Two different classes of oxygen-sensitive ahpC mutants
      in the type strain (ATCC 43504) were recently described (A. A. Olczak, J. W.
      Olson, and R. J. Maier, J. Bacteriol. 184:3186-3193, 2002). The same two classes
      of mutants were recovered upon ahpC mutagenesis of the mouse-adapted strain, SS1.
      Neither of these mutants was able to colonize mouse stomachs, whereas 78% of the
      mice inoculated with the parent strain became H. pylori positive.

PMID- 12496217
TI  - Biodefense-driven murine model of pneumonic melioidosis.
AB  - A whole-body mouse model of pneumonic melioidosis was established for future
      evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of
      Burkholderia pseudomallei strain 1026b for BALB/c and C57BL/6 mice and the times
      to death, dissemination in organs, and tissue loads after exposure of the mice to
      low- and high-dose aerosols are reported. In addition, rpsL mutant backgrounds
      were attenuated in this acute model of disease.

PMID- 12496218
TI  - Treatment of neonatal abstinence syndrome.
AB  - Neonatal abstinence syndrome (NAS) is suffered by infants withdrawing from
      substances on which they have become physically dependent after in utero
      exposure. They may require prolonged treatment and spend weeks or even months in
      hospital. A wide range of drugs have been used to treat NAS. The efficacy of few,
      however, have been adequately investigated. Evidence suggests that opioids are
      the most appropriate, at least in infants exposed to diamorphine or methadone. In
      all "head to head" trials, diazepam has been shown to be ineffective. Morphine
      and methadone are currently the most commonly prescribed opioids to treat NAS,
      but randomised trials have not been undertaken to determine which is the more
      beneficial. Many infants with NAS have been exposed to multiple substances in
      utero. Further research is required into whether a single opiate or a multiple
      drug regimen is the best option for such patients.

PMID- 12496219
TI  - Systematic review of intravenous immunoglobulin in haemolytic disease of the
      newborn.
AB  - OBJECTIVES: To assess the effectiveness of high dose intravenous immunoglobulin
      (HDIVIG) in reducing the need for exchange transfusion in neonates with proven
      haemolytic disease due to Rh and/or ABO incompatibility. To assess the
      effectiveness of HDIVIG in reducing the duration of phototherapy and hospital
      stay. DESIGN: Systematic review of randomised and quasi-randomised controlled
      trials comparing HDIVIG and phototherapy with phototherapy alone in neonates with
      Rh and/or ABO incompatibility. RESULTS: Significantly fewer infants required
      exchange transfusion in the HDIVIG group (relative risk (RR) 0.28 (95% confidence
      interval (CI) 0.17 to 0.47); number needed to treat 2.7 (95% CI 2.0 to 3.8)).
      Also hospital stay and duration of phototherapy were significantly reduced.
      CONCLUSION: HDIVIG is an effective treatment.

PMID- 12496220
TI  - Donor human milk versus formula for preventing necrotising enterocolitis in
      preterm infants: systematic review.
AB  - OBJECTIVES: To determine if enteral feeding with donor human milk compared with
      formula milk reduces the incidence of necrotising enterocolitis (NEC) in preterm
      or low birthweight infants. METHODS: Systematic review and meta-analysis of
      randomised controlled trials. RESULTS: Four small trials, all initiated more than
      20 years ago, fulfilled the prespecified inclusion criteria. None of the trials
      individually found any statistically significant difference in the incidence of
      NEC. However, meta-analysis found that feeding with donor human milk was
      associated with a significantly reduced relative risk (RR) of NEC. Infants who
      received donor human milk were three times less likely to develop NEC (RR 0.34;
      95% confidence interval (CI) 0.12 to 0.99), and four times less likely to have
      confirmed NEC (RR 0.25; 95% CI 0.06 to 0.98) than infants who received formula
      milk. CONCLUSIONS: It may be appropriate to consider further larger trials to
      compare growth, development, and the incidence of adverse outcomes, including
      NEC, in preterm infants who receive donor human milk versus formula milk.

PMID- 12496221
TI  - Outcomes for high risk New Zealand newborn infants in 1998-1999: a population
      based, national study.
AB  - OBJECTIVE: To determine short term morbidity and mortality outcomes, provision of
      care, and treatments for a national cohort of high risk infants born in 1998-1999
      and admitted to New Zealand neonatal intensive care units (NICUs). SETTING: All
      level III (six) and level II (13) NICUs in New Zealand. METHODS: Prospective
      audit by the Australian and New Zealand Neonatal Network (ANZNN) of all infants
      defined as "high risk" (born at < 32 weeks gestation or < 1500 g birth weight, or
      received assisted ventilation for four hours or more, or had major surgery). Data
      were collected from birth until discharge home or death. RESULTS: There were 3368
      high risk infants (3.0% of all live births), comprising 1241 (37%) < 32 weeks
      gestation, 1084 (32%) < 1500 g, 3156 (94%) who received assisted ventilation, and
      243 (7%) who received major surgery (categories overlap). Most infants (87%)
      received some care in tertiary hospitals, and 13% were cared for entirely in non
      tertiary hospitals. Survival was 91% for infants < 32 weeks gestation, 97% for
      infants > or = 32 weeks gestation who received assisted ventilation, and 92% for
      infants > or = 32 weeks gestation who had major surgery. The proportion of very
      preterm infants who survived free of early major morbidity was 11%, 28%, 53%,
      81%, and 90% for infants born at < 24, 24-25, 26-27, 28-29, and 30-31 weeks
      gestation respectively. CONCLUSIONS: These unique population based national data
      provide contemporary information on the care and early morbidity and mortality
      outcomes for all high risk infants, whether cared for in hospitals with level III
      or level II NICUs.

PMID- 12496222
TI  - Improved outcomes for very low birthweight infants: evidence from New Zealand
      national population based data.
AB  - OBJECTIVE: To compare the survival and short term morbidity of all New Zealand
      very low birthweight (VLBW) infants born in two epochs, 1986 and 1998-1999.
      SETTING: All level III and level II neonatal intensive care units (NICUs) in New
      Zealand. METHODS: In 1986, data were prospectively collected for a study of
      retinopathy of prematurity (ROP). In 1998-1999, prospective data were collected
      by the Australian and New Zealand Neonatal Network (ANZNN). Both cohorts included
      all VLBW infants born during the calendar year and admitted to a NICU. Data were
      collected from birth until discharge home or death. RESULTS: More VLBW infants
      were admitted for care in 1998-1999 (n = 1084, 0.96% of livebirths) than in 1986
      (n = 413, 0.78% of livebirths; p < 0.001), including a higher proportion of VLBW
      infants of < 1000 g birth weight (38% v 32% respectively; p < 0.05). Survival to
      discharge home increased from 81.8% in 1986 to 90.3% in 1998-1999 (p < 0.001).
      The 1998-1999 cohort had a higher proportion of infants born in a hospital with a
      level III NICU (87% v 72% in 1986; p < 0.001) and receiving antenatal
      corticosteroids (80% v 58% in 1986; p < 0.001). In 1998-1999, the incidence of
      several morbidities had decreased compared with 1986, including oxygen dependency
      at 28 days (29% v 39% respectively; p = 0.001) and at 36 weeks postmenstrual age
      (16% v 23%; p = 0.002), grade 1 intraventricular haemorrhage (IVH) (8% v 24%; p <
      0.001), grade 2/3 IVH (5% v 11%; p < 0.001), and stage 3/4 ROP for infants < 1000
      g (6% v 13%; p < 0.001). CONCLUSIONS: The outlook for VLBW infants in New Zealand
      has improved since 1986.

PMID- 12496223
TI  - A national two year follow up study of extremely low birthweight infants born in
      1996-1997.
AB  - OBJECTIVE: To study neurodevelopmental outcome in a two year cohort of extremely
      low birthweight (ELBW) infants at 18 months corrected age, to compare the
      development of the ELBW infant subcohort with that of control children, and to
      find risk factors associated with unfavourable outcome. STUDY DESIGN: All 211
      surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996-1997 were
      included in a national survey. The ELBW infants (n = 78) who were born and
      followed in Helsinki University Hospital belonged to a regional subcohort and
      were compared with a control group of 75 full term infants. A national follow up
      programme included neurological, speech, vision, and hearing assessments at 18
      months of corrected age. Bayley infant scale assessment was performed on the
      subcohort and their controls at 24 months of age. Risk factors for unfavourable
      outcome were estimated using logistic and linear regression models. RESULTS: The
      prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic
      abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of
      children, and 18% were classified as severely impaired. The prevalence of
      ophthalmic abnormalities decreased with increasing birth weight and gestational
      age, but the prevalence of other impairments did not. In the subcohort, a
      positive correlation was found between the date of birth and Bayley scores.
      CONCLUSION: Ophthalmic abnormalities decreased with increasing birth weight and
      gestational age, but no other outcome differences were found between birthweight
      groups or in surviving ELBW infants born at 22-26 weeks gestation. The prognosis
      in the regional subcohort seemed to improve during the short study period, but
      this needs to be confirmed.

PMID- 12496224
TI  - Excess risk of mortality in very low birthweight triplets: a national, population
      based study.
AB  - BACKGROUND: Neonatal morbidity and mortality differ between singletons, twins,
      and triplets. OBJECTIVE: To evaluate whether plurality is associated with excess
      risk of neonatal morbidity and poor outcome (death, chronic lung disease, or
      adverse neurological findings) in very low birthweight (VLBW) infants from a
      national, population based cohort. METHODS: The Israel national VLBW infant
      database has prospectively collected extensive perinatal and neonatal data on all
      liveborn VLBW infants since 1995. The study sample (n = 5594) consisted of all
      singletons (n = 3717) and all complete sets of twins (n = 1394) and triplets (n =
      483) born during 1995-1999. To account for differences in case-mix, both
      univariate and multivariate comparisons that included confounding variables such
      as antenatal steroid treatment and mode of delivery were performed for each of
      the outcome variables. RESULTS: There was a small inverse correlation between
      gestational age (GA) and birth weight (BW) and the number of fetuses (singletons:
      GA 28.9 (2.6) weeks, BW 1096 (269) g; twins: GA 28.4 (2.3) weeks, BW 1062 (271)
      g; triplets: GA 28.5 (2.4) weeks, BW 1049 (259) g). Triplets were significantly
      more likely to have been conceived following fertility treatments, to have
      received antenatal steroids, and to be delivered by caesarean section.
      Respiratory distress syndrome was significantly more common in twins and triplets
      in spite of the increased exposure to antenatal steroids. Multivariate logistic
      regression analysis using all significant perinatal covariates showed that
      triplets were at increased risk of death (odds ratio (OR) 1.54, 95% confidence
      interval (CI) 1.13 to 2.11), but not of adverse neurological outcome (OR 1.29,
      95% CI 0.91 to 1.85) or chronic lung disease (OR 0.69, 95% CI 0.46 to 1.02).
      CONCLUSION: Despite considerable differences in the incidence of confounding
      variables between the groups, VLBW triplets are at increased risk of death
      compared with twins and singletons. In addition, VLBW twins and triplets more
      often have respiratory distress syndrome but not chronic lung disease or adverse
      neurological findings.

PMID- 12496225
TI  - Recombinant erythropoietin and blood transfusion in selected preterm infants.
AB  - OBJECTIVES: To comprehensively identify preterm infants likely to require blood
      transfusion and to investigate the effectiveness of recombinant erythropoietin in
      this high risk subgroup. DESIGN: Double blind randomised controlled trial.
      SETTING: Neonatal Intensive Care Unit, Middlemore Hospital, Auckland, New
      Zealand. PATIENTS: Preterm infants < 33 weeks gestation and < 1700 g birth weight
      meeting specific criteria indicating a high possibility of requiring blood
      transfusion. INTERVENTIONS: Predictors of blood transfusion were determined by
      analysis of preterm infants admitted to a neonatal intensive care unit over a two
      year period. Using the criteria developed, high risk infants entered the study
      and received erythropoietin or sham treatment until 34 weeks completed gestation.
      The sample size was calculated to detect a reduction of one blood transfusion per
      infant (significance level 5%, power 80%). RESULTS: The selection criteria had a
      positive predictive value for transfusion of 91% and a negative predictive value
      of 94%. Mean birth weights and gestational ages were similar in the two groups.
      Absolute reticulocyte counts and haemoglobin values were higher in the group
      receiving erythropoietin. There was no significant difference in the number of
      blood transfusions received in the treatment and control groups. However,
      comparing transfusions given to < 1000 g infants after 30 days of age, there were
      significantly fewer transfusions in the erythropoietin group (mean (SD) 0.5 (0.7)
      in those receiving erythropoietin and 1.6 (1.1) in the controls). No adverse
      effects were noted. CONCLUSIONS: The selection criteria for the study were highly
      predictive of subsequent transfusion. In the group receiving erythropoietin, a
      reduction in transfusion requirements was apparent only in the < 1000 g
      birthweight group after 1 month of age.

PMID- 12496226
TI  - Growth and body composition in preterm infants with bronchopulmonary dysplasia.
AB  - OBJECTIVE: To compare growth and body composition in preterm infants with
      bronchopulmonary dysplasia (BPD) with normal healthy term infants during the
      first year of life. DESIGN: Twenty nine preterm infants with BPD (mean (SD)
      gestational age 27.1 (1.6) weeks; birth weight 852 (173) g) were followed
      prospectively. Anthropometry and body composition determined by total body
      electrical conductivity were measured and compared with those of healthy term
      infants at the same post-term age. RESULTS: In infants with BPD, the mean weight
      standard deviation scores (SD scores) 6 weeks after term were significantly lower
      (-1.44 and -2.68, boys and girls respectively) than in healthy term infants of
      the same age and did not improve during the first year. The mean length SD score
      was significantly lower in infants with BPD 6 weeks after term than in healthy
      term infants of the same age, and, although it improved significantly during the
      first year, the mean length SD score in girls with BPD was significantly below 0
      12 months after term. In infants with BPD, the mean free fat mass (FFM) SD score
      and the mean total body fat (TBF) SD score at 6 weeks post-term age were
      significantly below 0. The mean FFM SD scores (-1.01 and -2.56, boys and girls
      respectively) and the mean TBF SD scores (-1.14 and -2.40, boys and girls
      respectively) 12 months after term were significantly lower than in healthy term
      infants of the same age. CONCLUSIONS: Preterm infants with BPD have impaired
      growth, with a deficit in TBF and FFM already 6 weeks after term; FFM and TBF
      remain low compared with healthy term infants during the first year of life.
      Nutritional intervention studies in infants with BPD are needed to evaluate if
      nutrition is the major determinant of growth and body composition or if this
      pattern of growth in preterm infants with BPD is the result of disturbed
      endocrine control.

PMID- 12496227
TI  - Intestinal permeability in relation to birth weight and gestational and postnatal
      age.
AB  - OBJECTIVE: To determine the relation between intestinal permeability and birth
      weight, gestational age, postnatal age, and perinatal risk factors in neonates.
      STUDY DESIGN: Intestinal permeability was measured by the sugar absorption test
      within two days of birth and three to six days later in preterm and healthy term
      infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is
      measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol.
      RESULTS: A first sugar absorption test was performed in 116 preterm (26-36 weeks
      gestation) and 16 term infants. A second test was performed in 102 preterm and
      nine term infants. In the preterm infants, the lactulose/mannitol ratio was not
      related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p =
      0.43). The median lactulose/mannitol ratio was higher if measured less than two
      days after birth than when measured three to six days later (0.427 and 0.182
      respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm
      infants than term infants if measured within the first 2 days of life (0.404 and
      0.170 respectively, p < 0.001), but not different three to six days later (0.182
      and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal
      risk factors, only umbilical arterial pH correlated with the lactulose/mannitol
      ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05).
      CONCLUSIONS: In preterm infants (26-36 weeks gestation), intestinal permeability
      is not related to gestational age or birth weight but is higher during the first
      2 days of life than three to six days later. It is higher in preterm infants than
      in healthy term infants only if measured within two days of birth. This suggests
      rapid postnatal adaptation of the small intestine in preterm infants.

PMID- 12496228
TI  - Iodine deficiency associated with parenteral nutrition in extreme preterm
      infants.
AB  - Infants are in negative iodine balance on current standard regimens of total
      parenteral nutrition, with a mean iodine intake of 3 micro g/kg/day (150
      ml/kg/day). The recommended enteral intake of iodine for preterm infants is 30
      micro g/kg/day. Gastrointestinal absorption of iodine is high, suggesting that
      parenteral intakes should approach enteral recommendations.

PMID- 12496229
TI  - Effect of a fourth Haemophilus influenzae type b immunisation in preterm infants
      who received dexamethasone for chronic lung disease.
AB  - AIM: To assess whether a fourth Hib polysaccharide-tetanus protein conjugate
      vaccine (PRP-T) would improve antibody response in preterm infants previously
      treated with dexamethasone for chronic lung disease. METHODS: In a pilot study 12
      infants born at less than 30 weeks gestation who had received corticosteroids
      were given a supplementary Hib dose six weeks after completion of the primary
      immunisation course. Serum samples obtained before and at eight weeks following
      the fourth Hib dose were analysed for total level and avidity of anti-PRP
      antibody. RESULTS: There was no significant increase in the geometric mean titre
      (GMT) of anti-PRP antibody resulting from the fourth Hib immunisation (GMT: pre
      2.35 micro g/ml, post 2.24 micro g/ml, p = 0.79). A subgroup of six infants had
      subprotective antibody levels (<1.0 micro g/ml) after the primary immunisation
      course, which remained subprotective following the extra Hib immunisation.
      Despite the poor response in total antibody level, the study group showed a
      significant rise in PRP specific IgG avidity following the fourth immunisation
      (GMAI: pre 0.076, post 0.138, p = 0.043). CONCLUSION: An additional Hib
      immunisation given to recently steroid treated preterm infants six weeks after
      completion of the primary schedule did not augment primary immunogenicity.
      However, increasing avidity may imply successful priming and long term immunity
      to Hib.

PMID- 12496230
TI  - An inadequate glycaemic response to glucagon is linked to insulin resistance in
      preterm infants?
AB  - AIMS: To define clinical, metabolic, and hormonal characteristics of preterm
      infants relative to glucagon responsiveness. METHODS: Two phase study of 78
      preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating
      discharge home at 36 weeks mean corrected gestation. In phase 1 infants were
      fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic
      profiles were obtained at completion. Phase 2 was performed the following day. A
      feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro
      g/kg). Main outcome measures were measurements of blood glucose and lactate
      concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes
      for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was
      defined as an adequate response to glucagon. An inadequate glycaemic response was
      <1 mmol/l (23 infants). RESULTS: Several differences in fasting blood glucose and
      hormone concentrations were identified in infants with an inadequate glycaemic
      response to glucagon compared to those with an adequate response: relative
      fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting
      hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon
      ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index
      (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict
      response to glucagon. CONCLUSION: Some preterm infants show an inadequate
      glycaemic response to glucagon and have features suggestive of insulin
      resistance. The potential long term implications of such insulin resistance may
      have appreciable public health consequences.

PMID- 12496232
TI  - Paediatricians' perception of the use of extracorporeal membrane oxygenation to
      treat meconium aspiration syndrome.
AB  - This questionnaire study was designed to determine how consultant paediatricians
      perceived the value of extracorporeal membrane oxygenation (ECMO) in the
      treatment of meconium aspiration syndrome (MAS). A significant number believed
      that the survival of infants with MAS who received ECMO was lower than reported.
      Early discussion with an ECMO centre will ensure appropriate timing of referral.

PMID- 12496231
TI  - S100 protein content of umbilical cord blood in healthy newborns in relation to
      mode of delivery.
AB  - BACKGROUND: Early detection and quantification of brain damage in neonatal
      asphyxia is important. In adults, S100 protein in blood is associated with damage
      to the central nervous system. OBJECTIVE: To determine whether S100 protein can
      be detected in arterial and venous cord blood of healthy newborns and to relate
      S100 protein concentrations in cord blood to mode of delivery. METHOD: S100
      protein levels in umbilical cord blood of 81 healthy infants were determined.
      RESULTS: S100 protein was present in arterial (median concentration 1.62 micro
      g/l) and venous (median concentration 1.36 micro g/l) cord blood. Levels were
      significantly higher in vaginal births (median arterial concentration 1.72 micro
      g/l; median venous concentration 1.48 micro g/l) than births by caesarean section
      (1.51 micro g/l and 1.26 micro g/l respectively). CONCLUSION: More research is
      necessary to determine whether S100 protein is a useful marker in neonatal
      asphyxia.

PMID- 12496233
TI  - Extubation failure due to phrenic nerve injury.
AB  - A 26 week gestation infant had an increasingly elevated right hemidiaphragm
      following drainage of bilateral pleural effusions and failed extubation on
      numerous occasions. Electric stimulation of the phrenic nerves revealed absent
      activity on the right, indicating phrenic nerve injury from chest tube drain
      insertion. Diaphragmatic plication was performed and the infant successfully
      extubated four days later.

PMID- 12496234
TI  - Fetal meconium peritonitis: the "vanishing hydrocele" sign.

PMID- 12496235
TI  - Neonatal gastrointestinal perforation.

PMID- 12496236
TI  - Erich Bracht (1882-1969) of Berlin and his "breech" manoeuvre.
AB  - Erich Bracht, a German gynaecologist, described in 1935 the manoeuvre named after
      him for delivering the frank breech with minimal interference. In spite of the
      reported success of his method, it received little attention in the United
      Kingdom or North America.

PMID- 12496237
TI  - Blood transfusion in preterm neonates.

PMID- 12496240
TI  - Studies on the different modes of action of the anticoagulant protease inhibitors
      DX-9065a and Argatroban. I. Effects on thrombin generation.
AB  - The present study began with mathematical modeling of how inhibitors of both
      factor Xa (fXa) and thrombin affect extrinsic pathway-triggered blood
      coagulation. Numerical simulation demonstrated a stronger inhibition of thrombin
      generation by a thrombin inhibitor than a fXa inhibitor, but both prolonged clot
      time to a similar extent when they were given an equal dissociation constant (30
      nm) for interaction with their respective target enzymes. These differences were
      then tested by comparison with the real inhibitors DX-9065a and argatroban,
      specific competitive inhibitors of fXa and thrombin, respectively, with similar
      K(i) values. Comparisons were made in extrinsically triggered human citrated
      plasma, for which endogenous thrombin potential and clot formation were
      simultaneously measured with a Wallac multilabel counter equipped with both
      fluorometric and photometric detectors and a fluorogenic reporter substrate. The
      results demonstrated stronger inhibition of endogenous thrombin potential by
      argatroban than by DX-9065a, especially when coagulation was initiated at higher
      tissue factor concentrations, while argatroban appeared to be slightly less
      potent in its ability to prolong clot time. This study demonstrates differential
      inhibition of thrombin generation by fXa and thrombin inhibitors and has
      implications for the pharmacological regulation of blood coagulation by the
      anticoagulant protease inhibitors.

PMID- 12496241
TI  - Direct interaction with a kinesin-related motor mediates transport of mammalian
      discs large tumor suppressor homologue in epithelial cells.
AB  - Membrane-associated guanylate kinase homologues (MAGUKs) are generally found
      under the plasma membrane of cell-cell contact sites and function as scaffolding
      proteins by linking cytoskeletal and signaling molecules to transmembrane
      receptors. The correct targeting of MAGUKs is essential for their receptor
      clustering function; however, the molecular mechanism of their intracellular
      transport is unknown. Here, we show that the guanylate kinase-like domain of
      human discs large protein binds directly within the amino acids 607-831 of the
      stalk domain of GAKIN, a kinesin-like protein of broad distribution. The primary
      structure of the binding segment, termed MAGUK binding stalk domain, is conserved
      in Drosophila kinesin-73 and some other motor and non-motor proteins. This stalk
      segment is not found in GKAP, a synaptic protein that interacts with the
      guanylate kinase-like domain, and unlike GKAP, the binding of GAKIN is not
      regulated by the intramolecular interactions within the discs large protein. The
      recombinant motor domain of GAKIN is an active microtubule-stimulated ATPase with
      k(cat) = 45 s(-1), K(0.5 (MT)) = 0.1 microm. Overexpression of green fluorescent
      protein-fused GAKIN in Madin-Darby canine kidney epithelial cells induced long
      projections with both GAKIN and endogenous discs large accumulating at the tip of
      these projections. Importantly, the accumulation of endogenous discs large was
      eliminated when a mutant GAKIN lacking its motor domain was overexpressed under
      similar conditions. Taken together, our results indicate that discs large is a
      cargo molecule of GAKIN and suggest a mechanism for intracellular trafficking of
      MAGUK-laden vesicles to specialized membrane sites in mammalian cells.

PMID- 12496242
TI  - A new member of the LIM protein family binds to filamin B and localizes at stress
      fibers.
AB  - Human filamins are 280-kDa proteins containing an N-terminal actin-binding domain
      followed by 24 characteristic repeats. They also interact with a number of other
      cellular proteins. All of those identified to date, with the exception of actin,
      bind to the C-terminal third of a filamin. In a yeast two-hybrid search of a
      human placental library, using as bait repeats 10-18 of filamin B, we isolated a
      cDNA coding for a novel 374 amino acid protein containing a proline-rich domain
      near its N terminus and two LIM domains at its C terminus. We term this protein
      filamin-binding LIM protein-1, FBLP-1. Yeast two-hybrid studies with deletion
      mutants localized the areas of interaction in FBLP-1 to its N-terminal domain and
      in filamin B to repeats 10-13. FBLP-1 mRNA was detected in a variety of tissues
      and cells including platelets and endothelial cells. We also have identified two
      FBLP-1 variants. Both contain three C-terminal LIM domains, but one lacks the N
      terminal proline-rich domain. Transfection of FBLP-1 into 293A cells promoted
      stress fiber formation, and both FBLP-1 and filamin B localized to stress fibers
      in the transfected cells. The association between filamin B and FBLP-1 may play a
      hitherto unknown role in cytoskeletal function, cell adhesion, and cell motility.

PMID- 12496243
TI  - Structure of Escherichia coli 5'-methylthioadenosine/ S-adenosylhomocysteine
      nucleosidase inhibitor complexes provide insight into the conformational changes
      required for substrate binding and catalysis.
AB  - 5'-Methylthioadenosine/S-adenosylhomocysteine (MTA/AdoHcy) nucleosidase is a key
      enzyme in a number of critical biological processes in many microbes. This
      nucleosidase catalyzes the irreversible hydrolysis of the N(9)-C(1') bond of MTA
      or AdoHcy to form adenine and the corresponding thioribose. The key role of the
      MTA/AdoHcy nucleosidase in biological methylation, polyamine biosynthesis,
      methionine recycling, and bacterial quorum sensing has made it an important
      antimicrobial drug target. The crystal structures of Escherichia coli MTA/AdoHcy
      nucleosidase complexed with the transition state analog, formycin A (FMA), and
      the nonhydrolyzable substrate analog, 5'-methylthiotubercidin (MTT) have been
      solved to 2.2- and 2.0-A resolution, respectively. These are the first MTA/AdoHcy
      nucleosidase structures to be solved in the presence of inhibitors. These
      structures clearly identify the residues involved in substrate binding and
      catalysis in the active site. Comparisons of the inhibitor complexes to the
      adenine-bound MTA/AdoHcy nucleosidase (Lee, J. E., Cornell, K. A., Riscoe, M. K.,
      and Howell, P. L. (2001) Structure (Camb.) 9, 941-953) structure provide evidence
      for a ligand-induced conformational change in the active site and the substrate
      preference of the enzyme. The enzymatic mechanism has been re-examined.

PMID- 12496244
TI  - Modulation of estrogen receptor alpha function and stability by tamoxifen and a
      critical amino acid (Asp-538) in helix 12.
AB  - Estrogen receptor alpha (ER) is a ligand-activated transcription factor
      implicated in breast cancer growth. Selective estrogen receptor modulators
      (SERMs), such as tamoxifen (4-OHT), bind to the ER and affect the position of
      helix 12, thereby influencing coregulator binding and ER transcriptional
      activation. Previous studies have shown that a triple mutation in helix 12 (3m;
      D538A/E542A/D545A) caused a change in ER stability and obliterated 4-OHT action
      (Liu, H., Lee, E. S., de los Reyes, A., Zapf, J. W., and Jordan, V. C. (2001)
      Cancer Res. 61, 3632-3639). Two approaches were taken to determine the role of
      individual mutants (D538A, L540Q, E542A, and D545A) on the activity and stability
      of the 4-OHT.ER complex. First, mutants were evaluated using transient
      transfection into ER-negative T47D:C4:2 cells with an ERE3-luciferase reporter,
      and second, transforming growth factor alpha (TGFalpha) mRNA was used as a gene
      target in situ for stable transfectants of MDA-MB-231 cells. Transcriptional
      activity occurred in the presence of estrogen in all of the mutants, although a
      decreased response was observed in the L540Q, 3m, and D538A cells. The 3m and
      D538A mutants lacked any estrogenic responsiveness to 4-OHT, whereas the other
      mutations retained estrogen-like activity with 4-OHT. Unlike the other mutants,
      the ER was degraded in the D538A mutant with 4-OHT treatment. However, increasing
      the protein levels of the mutant with the proteasome inhibitor MG132 did not
      restore the ability of 4-OHT to induce TGFalpha mRNA. We suggest that Asp-538 is
      a critical amino acid in helix 12 that not only reduces the estrogen-like actions
      of 4-OHT but also facilitates the degradation of the 4-OHT.D538A complex. These
      data further illustrate the complex role of specific surface amino acids in the
      modulation of the concentration and the estrogenicity of the 4-OHT.ER complex.

PMID- 12496245
TI  - Fast kinetics of Taxol binding to microtubules. Effects of solution variables and
      microtubule-associated proteins.
AB  - The kinetics of Taxol association to and dissociation from stabilized
      microtubules has been measured by competition with the reference fluorescent
      derivative Flutax-1 (Diaz, J. F., Strobe, R., Engelborghs, Y., Souto, A. A., and
      Andreu, J. M. (2000) J. Biol. Chem. 275, 26265-26276). The association rate
      constant at 37 degrees C is k(+) = (3.6 +/- 0.1) x 10(6) m(-1) s(-1). The
      reaction profile is similar to that of the first step of Flutax-1 binding, which
      probably corresponds to the binding of the Taxol moiety. The rate constant of the
      initial binding of Flutax-1 is inversely proportional to the viscosity of the
      solution, which is compatible with a diffusion-controlled reaction. Microtubule
      associated proteins bound to the microtubule outer surface slow down the binding
      of Flutax-1 and Flutax-2 10-fold. The binding site is fully accessible to Flutax
      2 in native cytoskeletons of PtK2 cells; the observed kinetic rates of Flutax-2
      microtubule staining and de-staining are similar to the reaction rates with
      microtubule associated proteins-containing microtubules. The kinetic data prove
      that taxoids bind directly from the bulk solution to an exposed microtubule site.
      Several hypotheses have been analyzed to potentially reconcile these data with
      the location of a Taxol-binding site at the model microtubule lumen, including
      dynamic opening of the microtubule wall and transport from an initial Taxol
      binding site at the microtubule pores.

PMID- 12496246
TI  - Molecular basis of sulfonylurea herbicide inhibition of acetohydroxyacid
      synthase.
AB  - Acetohydroxyacid synthase (AHAS) (acetolactate synthase, EC ) catalyzes the first
      step in branched-chain amino acid biosynthesis and is the target for sulfonylurea
      and imidazolinone herbicides. These compounds are potent and selective
      inhibitors, but their binding site on AHAS has not been elucidated. Here we
      report the 2.8 A resolution crystal structure of yeast AHAS in complex with a
      sulfonylurea herbicide, chlorimuron ethyl. The inhibitor, which has a K(i) of 3.3
      nm, blocks access to the active site and contacts multiple residues where
      mutation results in herbicide resistance. The structure provides a starting point
      for the rational design of further herbicidal compounds.

PMID- 12496247
TI  - High resolution structure, stability, and synaptotagmin binding of a truncated
      neuronal SNARE complex.
AB  - The structure of a truncated SNARE complex has been solved to 1.4-A resolution
      revealing a stabilizing salt bridge, sites of hydration, and conformational
      variability of the ionic central layer that were not observed in a previously
      published structure at 2.4-A resolution (Sutton, R. B., Fasshauer, D., Jahn, R.,
      and Brunger, A. T. (1998) Nature 395, 347-353). The truncated complex lacks
      residues involved in phospholipid binding and denatures at a lower temperature
      than longer complexes as assessed by SDS and circular dichroism thermal melts.
      The truncated SNARE complex is monomeric, and it retains binding to synaptotagmin
      I.

PMID- 12496248
TI  - The C-terminal PDZ-ligand of JAGGED1 is essential for cellular transformation.
AB  - JAGGED1 is a member of the Delta/Serrate/Lag-2 (DSL) family of proteins that are
      cell-bound ligands for Notch receptors. Initiation of Notch signaling occurs
      through a series of proteolytic events upon the binding of Notch to a DSL protein
      presented on neighboring cells. Whether DSL proteins themselves are capable of
      initiating an intrinsic signaling mechanism within the cell they are expressed is
      not known. Aberrant misexpression of JAGGED1 and DELTA1 has been documented in
      several human tumors; however, the mechanism by which misexpression of JAGGED1
      contributes to oncogenesis has not been elucidated. We report that expression of
      human JAGGED1 transforms RKE cells in culture, therefore providing a model system
      to elucidate the function of DSL proteins. JAGGED1-mediated transformation occurs
      in a dose-dependent manner and requires a PDZ-ligand at the C terminus. Mutation
      of the PDZ-ligand did not affect the ability of JAGGED1 to initiate Notch
      signaling in neighboring cells. However, the PDZ-ligand is required for changes
      in the expression of JAGGED1 target genes and transcriptional activation of
      luciferase reporter constructs. Our data indicate the existence of a novel PDZ
      dependent signaling pathway intrinsic to JAGGED1. We propose a bi-directional
      signaling model such that DSL proteins may have two distinct functions: to
      initiate Notch signaling in a neighboring cell and to initiate a PDZ-dependent
      signaling mechanism in the DSL-expressing cell. Moreover, we conclude that this
      intrinsic signaling mechanism of JAGGED1 may partly provide a link between
      aberrant misexpression of JAGGED1 and tumorigenesis.

PMID- 12496250
TI  - Parathyroid hormone regulation of type II sodium-phosphate cotransporters is
      dependent on an A kinase anchoring protein.
AB  - Parathyroid hormone inhibits sodium-phosphate cotransport in proximal renal
      tubule cells through activation of several kinases. We tested the hypothesis that
      the activity of these kinases was coordinated by an A kinase anchoring protein
      (AKAP) by demonstrating that the type II sodium-phosphate cotransporter (NaPi-4)
      physically associated with an AKAP and that this association was necessary for
      regulation of phosphate transport by parathyroid hormone. Immunoprecipitation
      with anti-NaPi-4 antiserum and glutathione S-transferase pull-down with GST-NaPi
      4 showed that NaPi-4 associated with AKAP79, protein kinase A catalytic and
      regulatory subunits, and the parathyroid hormone receptor in opossum kidney
      cells. When the regulatory subunit of protein kinase A was uncoupled from the
      AKAP by a competing peptide, parathyroid hormone lost the ability to inhibit
      phosphate transport. This result was confirmed by co-transfecting HEK293 cells
      with the sodium-phosphate cotransporter and wild type AKAP, a mutant AKAP79, or
      the empty vector. 8-Bromo-cAMP was able to inhibit phosphate transport in cells
      expressing the wild type AKAP79 but not empty vector or mutant AKAP79. We
      conclude that parathyroid hormone inhibits proximal renal tubule sodium-phosphate
      cotransport through a signaling complex dependent upon an AKAP.

PMID- 12496249
TI  - Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP as a stimulus for Ca2+-induced
      Ca2+ release and exocytosis in pancreatic beta-cells.
AB  - The second messenger cAMP exerts powerful stimulatory effects on Ca(2+) signaling
      and insulin secretion in pancreatic beta-cells. Previous studies of beta-cells
      focused on protein kinase A (PKA) as a downstream effector of cAMP action.
      However, it is now apparent that cAMP also exerts its effects by binding to cAMP
      regulated guanine nucleotide exchange factors (Epac). Although one effector of
      Epac is the Ras-related G protein Rap1, it is not fully understood what the
      functional consequences of Epac-mediated signal transduction are at the cellular
      level. 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3'-5'-cyclic monophosphate (8
      pCPT-2'-O-Me-cAMP) is a newly described cAMP analog, and it activates Epac but
      not PKA. Here we demonstrate that 8-pCPT-2'-O-Me-cAMP acts in human pancreatic
      beta-cells and INS-1 insulin-secreting cells to mobilize Ca(2+) from
      intracellular Ca(2+) stores via Epac-mediated Ca(2+)-induced Ca(2+) release
      (CICR). The cAMP-dependent increase of [Ca(2+)](i) that accompanies CICR is shown
      to be coupled to exocytosis. We propose that the interaction of cAMP and Epac to
      trigger CICR explains, at least in part, the blood glucose-lowering properties of
      an insulinotropic hormone (glucagon-like peptide-1, also known as GLP-1) now
      under investigation for use in the treatment of type-2 diabetes mellitus.

PMID- 12496251
TI  - Metabolism of homocysteine-thiolactone in plants.
AB  - Editing of the amino acid homocysteine (Hcy) by certain aminoacyl-tRNA
      synthetases results in the formation of an intramolecular thioester, Hcy
      thiolactone. Here we show that the plant yellow lupin, Lupinus luteus, has the
      ability to synthesize Hcy-thiolactone. The inhibition of methylation of Hcy to
      methionine by the anitifolate drug aminopterin results in greatly enhanced
      synthesis of Hcy-thiolactone by L. luteus plants. Methionine inhibits the
      synthesis of Hcy-thiolactone in L. luteus, suggesting involvement of methionyl
      tRNA synthetase. Consistent with this suggestion is our finding that the plant
      Oryza sativa methionyl-tRNA synthetase, expressed in Escherichia coli, catalyzes
      conversion of Hcy to Hcy-thiolactone. We also show that Hcy is a component of L.
      luteus proteins, most likely due to facile reaction of Hcy-thiolactone with
      protein amino groups. In addition, L. luteus possesses constitutively expressed,
      highly specific Hcy-thiolactone-hydrolyzing enzyme. Thus, Hcy-thiolactone and Hcy
      bound to protein by an amide (or peptide) linkage (Hcy-N-protein) are significant
      components of plant Hcy metabolism.

PMID- 12496252
TI  - Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its
      interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor
      necrosis factor receptor-associated factor 6 (TRAF6) complex.
AB  - The signaling pathway downstream of the mammalian interleukin-1 receptor (IL
      1R)/Toll-like receptor (TLR) is evolutionally conserved with that mediated by the
      Drosophila Toll protein. Toll initiates its signal through the adapter molecule
      Tube and the serine-threonine kinase Pelle. Pelle is highly homologous to members
      of the IL-1R-associated kinase (IRAK) family in mammals. Recently, a novel Pelle
      interacting protein called Pellino was identified in Drosophila. We now report a
      mammalian counterpart of Pellino, termed Pellino 1, which is required for NF
      kappa B activation and IL-8 gene expression in response to IL-1, probably through
      its signal-dependent interaction with IRAK4, IRAK, and the tumor necrosis factor
      receptor-associated factor 6 (TRAF6). The Pellino 1-IRAK-IRAK4-TRAF6 signaling
      complex is likely to be intermediate, located between the IL-1 receptor complex
      and the TAK1 complex in the IL-1 pathway.

PMID- 12496253
TI  - The factor IX gamma-carboxyglutamic acid (Gla) domain is involved in interactions
      between factor IX and factor XIa.
AB  - During hemostasis, factor IX is activated to factor IXabeta by factor VIIa and
      factor XIa. The glutamic acid-rich gamma-carboxyglutamic acid (Gla) domain of
      factor IX is involved in phospholipid binding and is required for activation by
      factor VIIa. In contrast, activation by factor XIa is not phospholipid-dependent,
      raising questions about the importance of the Gla for this reaction. We examined
      binding of factors IX and IXabeta to factor XIa by surface plasmon resonance.
      Plasma factors IX and IXabeta bind to factor XIa with K(d) values of 120 +/- 11
      nm and 110 +/- 8 nm, respectively. Recombinant factor IX bound to factor XIa with
      a K(d) of 107 nm, whereas factor IX with a factor VII Gla domain (rFIX/VII-Gla)
      and factor IX expressed in the presence of warfarin (rFIX-desgamma) did not bind.
      An anti-factor IX Gla monoclonal antibody was a potent inhibitor of factor IX
      binding to factor XIa (K(i) 34 nm) and activation by factor XIa (K(i) 33 nm). In
      activated partial thromboplastin time clotting assays, the specific activities of
      plasma and recombinant factor IX were comparable (200 and 150 units/mg), whereas
      rFIX/VII-Gla activity was low (<2 units/mg). In contrast, recombinant factor
      IXabeta and activated rFIX/VIIa-Gla had similar activities (80 and 60% of plasma
      factor IXabeta), indicating that both proteases activate factor X and that the
      poor activity of zymogen rFIX/VII-Gla was caused by a specific defect in
      activation by factor XIa. The data demonstrate that factor XIa binds with
      comparable affinity to factors IX and IXabeta and that the interactions are
      dependent on the factor IX Gla domain.

PMID- 12496254
TI  - An enthusiasm for metabolism.

PMID- 12496255
TI  - The cell surface receptor DC-SIGN discriminates between Mycobacterium species
      through selective recognition of the mannose caps on lipoarabinomannan.
AB  - Interactions between dendritic cells (DCs) and Mycobacterium tuberculosis, the
      etiological agent of tuberculosis, most likely play a key role in anti
      mycobacterial immunity. We have recently shown that M. tuberculosis binds to and
      infects DCs through ligation of the DC-specific intercellular adhesion molecule-3
      grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped
      lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin,
      suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we
      investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was
      found for slow growing mycobacteria, such as M. tuberculosis and the vaccine
      strain Mycobacterium bovis bacillus Calmette-Guerin, our data demonstrate that
      the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC
      SIGN. Consistent with the former finding, we show that M. smegmatis-derived
      lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits
      a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using
      enzymatically demannosylated and chemically deacylated ManLAM molecules, we
      demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol
      anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM
      interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and
      uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium
      chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium,
      in which ManLAM is capped with single mannose residues, was also poorly
      recognized by the lectin. Altogether, our results provide molecular insight into
      the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may
      act as a pattern recognition receptor and discriminate between Mycobacterium
      species through selective recognition of the mannose caps on LAM molecules.

PMID- 12496256
TI  - RANK ligand-induced elevation of cytosolic Ca2+ accelerates nuclear translocation
      of nuclear factor kappa B in osteoclasts.
AB  - RANK ligand (RANKL) induces activation of NFkappaB, enhancing the formation,
      resorptive activity, and survival of osteoclasts. Ca(2+) transduces many
      signaling events, however, it is not known whether the actions of RANKL involve
      Ca(2+) signaling. We investigated the effects of RANKL on rat osteoclasts using
      microspectrofluorimetry and patch clamp. RANKL induced transient elevation of
      cytosolic free Ca(2+) concentration ([Ca(2+)](i)) to maxima 220 nm above basal,
      resulting in activation of Ca(2+)-dependent K(+) current. RANKL elevated
      [Ca(2+)](i) in Ca(2+)-containing and Ca(2+)-free media, and responses were
      prevented by the phospholipase C inhibitor. Suppression of [Ca(2+)](i) elevation
      using the intracellular Ca(2+) chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid (BAPTA) abolished the ability of RANKL to enhance osteoclast
      survival. Using immunofluorescence, NFkappaB was found predominantly in the
      cytosol of untreated osteoclasts. RANKL induced transient translocation of
      NFkappaB to the nuclei, which was maximal at 15 min. or BAPTA delayed nuclear
      translocation of NFkappaB. Delays were also observed upon inhibition of
      calcineurin or protein kinase C. We conclude that RANKL acts through
      phospholipase C to release Ca(2+) from intracellular stores, accelerating nuclear
      translocation of NFkappaB and promoting osteoclast survival. Such cross-talk
      between NFkappaB and Ca(2+) signaling provides a novel mechanism for the temporal
      regulation of gene expression in osteoclasts and other cell types.

PMID- 12496257
TI  - Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin.
      Implications fpr metabolic regulation and bioactivity.
AB  - Acrp30/adiponectin is an adipocyte-specific secretory protein that has recently
      been implicated as a mediator of systemic insulin sensitivity with liver and
      muscle as target organs. Acrp30 is found as two forms in serum, as a lower
      molecular weight trimer-dimer and a high molecular weight complex. Little is know
      about the regulation and significance of these Acrp30 complexes in serum and
      about the events that lead to the generation of the bioactive ligand. Here, we
      show that there is a profound sexual dimorphism of Acrp30 levels and complex
      distribution in serum. Female mice display significantly higher levels of the
      high molecular weight complex in serum than males. In both females and males,
      levels of the high molecular weight complex are significantly reduced in response
      to a systemic increase of insulin. The ratio of the two complexes is restored
      upon normalization of glucose levels. Structurally, we show that oligomer
      formation of Acrp30 critically depends on disulfide bond formation mediated by
      Cys-39. Mutation of Cys-39 results in trimers that are subject to proteolytic
      cleavage in the collagenous domain. Surprisingly, Acrp30(C39S) or wild-type
      Acrp30 treated with dithiothreitol are significantly more bioactive than the
      higher order oligomeric forms of the protein with respect to reduction of serum
      glucose levels. Furthermore, treatment of primary hepatocytes with trimeric and
      higher order forms of Acrp30 confirms that the increased bioactivity seen in vivo
      is reflected in an augmented potency to reduce glucose output in the presence of
      gluconeogenic stimuli. Combined, these results shed new light on the regulation
      of this complex protein and suggest a new model for in vivo activation of the
      protein, implicating a serum reductase activity.

PMID- 12496258
TI  - Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular
      endothelial cells are mediated by CXCR2.
AB  - Angiogenesis plays a critical role in metastasis and tumor growth. Human tumors,
      including colorectal adenocarcinoma, secrete angiogenic factors, inducing
      proliferation and chemotaxis of microvascular endothelial cells, eventually
      leading to tumor neovascularization. The chemokine interleukin 8 (IL-8; CXCL8)
      exerts potent angiogenic properties on endothelial cells through interaction with
      its cognate receptors CXCR1 and CXCR2. As CXCR1 and CXCR2 expression is
      differentially regulated in tissue-specific endothelial cells and effects of IL-8
      on intestinal endothelial cells are not defined, we characterized the potential
      IL-8-induced angiogenic mechanisms in primary cultures of human intestinal
      microvascular endothelial cells (HIMEC) and IL-8 receptor expression in human
      intestinal microvessels. CXCR1 and CXCR2 expression on HIMEC were defined using
      reverse transcriptase-PCR, immunohistochemistry, flow cytometry, and Western blot
      analysis. IL-8-induced downstream signaling events were assessed using immunoblot
      analysis and immunofluorescence. The angiogenic effects of IL-8 on HIMEC were
      determined using proliferation and chemotaxis assays. HIMEC responded to IL-8
      with rapid stress fiber assembly, chemotaxis, enhanced proliferation, and
      phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2).
      HIMEC express CXCR2, but not CXCR1. Neutralizing antibodies to CXCR2 diminished
      IL-8-induced chemotaxis and stress fiber assembly. Specific inhibitors of ERK 1/2
      and phosphoinositide 3-kinase abrogated endothelial tube formation and IL-8
      induced chemotaxis in HIMEC. IL-8 elicits angiogenic responses in microvascular
      endothelial cells isolated from human intestine by engaging CXCR2. We confirmed
      tissue expression of CXCR2 in human intestinal microvessels. Supported by the
      notion that malignant colonic epithelial cells overexpress IL-8, CXCR2 blockade
      may be a novel target for anti-angiogenic therapy in colorectal adenocarcinoma.

PMID- 12496259
TI  - The adipocyte plasma membrane caveolin functional/structural organization is
      necessary for the efficient endocytosis of GLUT4.
AB  - It is well established that insulin stimulation of glucose uptake requires the
      translocation of intracellular localized GLUT4 protein to the cell surface
      membrane. This plasma membrane-redistributed GLUT4 protein was partially co
      localized with caveolin as determined by confocal fluorescent microscopy but was
      fully excluded from lipid rafts based upon Triton X-100 extractability.
      Cholesterol depletion with methyl-beta-cyclodextrin, filipin, or cholesterol
      oxidase resulted in an insulin-independent increase in the amount of plasma
      membrane-localized GLUT4 that was fully reversible by cholesterol replenishment.
      This basal accumulation of cell surface GLUT4 occurred due to an inhibition of
      GLUT4 endocytosis. However, this effect was not specific since cholesterol
      extraction also resulted in a dramatic inhibition of clathrin-mediated
      endocytosis as assessed by transferrin receptor internalization. To functionally
      distinguish between caveolin- and clathrin-dependent endocytic processes, we took
      advantage of a dominant-interfering caveolin 1 mutant (Cav1/S80E) that
      specifically disrupts caveolae organization. Expression of Cav1/S80E, but not the
      wild type (Cav1/WT) or Cav1/S80A mutant, inhibited cholera toxin B
      internalization without any significant effect on transferrin receptor
      endocytosis. In parallel, Cav1/S80E expression increased the amount of plasma
      membrane-localized GLUT4 protein in an insulin-independent manner. Although
      Cav1/S80E also decreased GLUT4 endocytosis, the extent of GLUT4 internalization
      was only partially reduced ( approximately 40%). In addition, expression of
      Cav1/WT and Cav1/S80A enhanced GLUT4 endocytosis by approximately 20%. Together,
      these data indicate that the endocytosis of GLUT4 requires clathrin-mediated
      endocytosis but that the higher order structural organization of plasma membrane
      caveolin has a significant influence on this process.

PMID- 12496260
TI  - A scavenger function for a Drosophila peptidoglycan recognition protein.
AB  - Recent studies of peptidoglycan recognition protein (PGRP) have shown that 2 of
      the 13 Drosophila PGRP genes encode proteins that function as receptors mediating
      immune responses to bacteria. We show here that another member, PGRP-SC1B, has a
      totally different function because it has enzymatic activity and thereby can
      degrade peptidoglycan. A mass spectrometric analysis of the cleavage products
      demonstrates that the enzyme hydrolyzes the lactylamide bond between the glycan
      strand and the cross-linking peptides. This result assigns the protein as an N
      acetylmuramoyl-l-alanine amidase (EC ), and the corresponding gene is thus the
      first of this class to be described from a eukaryotic organism. Mutant forms of
      PGRP-SC1B lacking a potential zinc ligand are enzymatically inactive but retain
      their peptidoglycan affinity. The immunostimulatory properties of PGRP-SC1B
      degraded peptidoglycan are much reduced. This is in striking contrast to lysozyme
      digested peptidoglycan, which retains most of its elicitor activity. This points
      toward a scavenger function for PGRP-SC1B. Furthermore, a sequence homology
      comparison with phage T7 lysozyme, also an N-acetylmuramoyl-l-alanine amidase,
      shows that as many as six of the Drosophila PGRPs could belong to this class of
      proteins.

PMID- 12496261
TI  - The two photocycles of photoactive yellow protein from Rhodobacter sphaeroides.
AB  - The absorption spectrum of the photoactive yellow protein from Rhodobacter
      sphaeroides (R-PYP) shows two maxima, absorbing at 360 nm (R-PYP(360)) and 446 nm
      (R-PYP(446)), respectively. Both forms are photoactive and part of a temperature-
      and pH-dependent equilibrium (Haker, A., Hendriks, J., Gensch, T., Hellingwerf,
      K. J., and Crielaard, W. (2000) FEBS Lett. 486, 52-56). At 20 degrees C, for PYP
      characteristic, the 446-nm absorbance band displays a photocycle, in which the
      depletion of the 446-nm ground state absorption occurs in at least three phases,
      with time constants of <30 ns, 0.5 micros, and 17 micros. Intermediates with both
      blue- and red-shifted absorption maxima are transiently formed, before a blue
      shifted intermediate (pB(360), lambda(max) = 360 nm) is established. The
      photocycle is completed with a monophasic recovery of the ground state with a
      time constant of 2.5 ms. At 7 degrees C these photocycle transitions are slowed
      down 2- to 3-fold. Upon excitation of R-PYP(360) with a UV-flash (330 +/- 50 nm)
      a species with a difference absorption maximum at approximately 435 nm is
      observed that returns to R-PYP(360) on a minute time scale. Recovery can be
      accelerated by a blue light flash (450 nm). R-PYP(360) and R-PYP(446) differ in
      their overall protein conformation, as well as in the isomerization and
      protonation state of the chromophore, as determined with the fluorescent polarity
      probe Nile Red and Fourier Transform Infrared spectroscopy, respectively.

PMID- 12496262
TI  - Identification of a novel domain of fibroblast growth factor 2 controlling its
      angiogenic properties.
AB  - Fibroblast growth factor 2 (FGF-2) is a potent factor modulating the activity of
      many cell types. Its dimerization and binding to high affinity receptors are
      considered to be necessary steps to induce FGF receptor phosphorylation and
      signaling activation. A structural analysis was carried out and a region
      encompassing residues 48-58 of human FGF-2 was identified, as potentially
      involved in FGF-2 dimerization. A peptide (FREG-48-58) derived from this region
      strongly and specifically inhibited FGF-2 induced proliferation and migration of
      primary bovine aorta endothelial cells (BAEC) in vitro, and markedly reduced FGF
      2-dependent angiogenesis in two distinct in vivo assays. To further investigate
      the role of region 48-58, a polyclonal antibody raised against FREG-(48-58) was
      tested and was found to block FGF-2 action in vitro. Human FGF-2 has three
      histidine residues, one falling within the region 48-58. Chemical modification of
      histidine residues blocked FGF-2 activity and FREG-(48-58) inhibitory effect in
      vitro, indicating that histidine residues, in particular the one within FREG-(48
      58) region, play a crucial role in the observed activity. Additional experiments
      showed that FREG-(48-58) specifically interacted with FGF-2, impaired FGF-2
      interaction with itself, with heparin and with FGF receptor 1, and inhibited FGF
      2-induced receptor phosphorylation and FGF-2 internalization. These data indicate
      for the first time that region 48-58 of FGF-2 is a functional domain controlling
      FGF-2 activity.

PMID- 12496263
TI  - Role of an intrasubunit disulfide in the association state of the cytosolic homo
      oligomer methionine adenosyltransferase.
AB  - Recombinant rat liver methionine adenosyltransferase has been refolded into fully
      active tetramers (MAT I) and dimers (MAT III), using as a source chaotrope
      solubilized aggregates resulting from specific washes of inclusion bodies. The
      conditions of refolding, dialysis in the presence of 10 mm dithiothreitol or 10
      mm GSH with 1 mm GSSG, allowed the production of both isoforms, the nature of the
      redox agent determining the capacity of the final product (MAT I/III) to
      interconvert. Refolding in the presence of 10 mm dithiothreitol yielded mainly
      MAT III in a concentration-dependent equilibrium with the homotetramer MAT I.
      However, refolding in the presence of the redox pair GSH/GSSG resulted in a
      stable MAT I and III mixture. Blockage of dimer-tetramer interconversion has been
      found related to the production of a single intramolecular disulfide in
      methionine adenosyltransferase during the GSH/GSSG folding process. The residues
      involved in this disulfide have been identified by mass spectrometry and using a
      set of single cysteine mutants as cysteines 35 and 61. In addition, a kinetic
      intermediate in the MAT I dissociation to MAT III has been detected. The
      physiological importance of these results is discussed in light of the structural
      and regulatory data available.

PMID- 12496264
TI  - alpha 11beta 1 integrin recognizes the GFOGER sequence in interstitial collagens.
AB  - The integrins alpha(1)beta(1), alpha(2)beta(1), alpha(10)beta(1), and
      alpha(11)beta(1) are referred to as a collagen receptor subgroup of the integrin
      family. Recently, both alpha(1)beta(1) and alpha(2)beta(1) integrins have been
      shown to recognize triple-helical GFOGER (where single letter amino acid
      nomenclature is used, O = hydroxyproline) or GFOGER-like motifs found in
      collagens, despite their distinct binding specificity for various collagen
      subtypes. In the present study we have investigated the mechanism whereby the
      latest member in the integrin family, alpha(11)beta(1), recognizes collagens
      using C2C12 cells transfected with alpha(11) cDNA and the bacterially expressed
      recombinant alpha(11) I domain. The ligand binding properties of alpha(11)beta(1)
      were compared with those of alpha(2)beta(1). Mg(2+)-dependent alpha(11)beta(1)
      binding to type I collagen required micromolar Ca(2+) but was inhibited by 1 mm
      Ca(2+), whereas alpha(2)beta(1)-mediated binding was refractory to millimolar
      concentrations of Ca(2+). The bacterially expressed recombinant alpha(11) I
      domain preference for fibrillar collagens over collagens IV and VI was the same
      as the alpha(2) I domain. Despite the difference in Ca(2+) sensitivity,
      alpha(11)beta(1)-expressing cells and the alpha(11) I domain bound to helical
      GFOGER sequences in a manner similar to alpha(2)beta(1)-expressing cells and the
      alpha(2) I domain. Modeling of the alpha I domain-collagen peptide complexes
      could partially explain the observed preference of different I domains for
      certain GFOGER sequence variations. In summary, our data indicate that the GFOGER
      sequence in fibrillar collagens is a common recognition motif used by
      alpha(1)beta(1), alpha(2)beta(1), and also alpha(11)beta(1) integrins. Although
      alpha(10) and alpha(11) chains show the highest sequence identity, alpha(2) and
      alpha(11) are more similar with regard to collagen specificity. Future studies
      will reveal whether alpha(2)beta(1) and alpha(11)beta(1) integrins also show
      overlapping biological functions.

PMID- 12496265
TI  - Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing
      mitochondrial reactive oxygen species production.
AB  - Inhibition of mitochondrial respiratory chain complex I by rotenone had been
      found to induce cell death in a variety of cells. However, the mechanism is still
      elusive. Because reactive oxygen species (ROS) play an important role in
      apoptosis and inhibition of mitochondrial respiratory chain complex I by rotenone
      was thought to be able to elevate mitochondrial ROS production, we investigated
      the relationship between rotenone-induced apoptosis and mitochondrial reactive
      oxygen species. Rotenone was able to induce mitochondrial complex I substrate
      supported mitochondrial ROS production both in isolated mitochondria from HL-60
      cells as well as in cultured cells. Rotenone-induced apoptosis was confirmed by
      DNA fragmentation, cytochrome c release, and caspase 3 activity. A quantitative
      correlation between rotenone-induced apoptosis and rotenone-induced mitochondrial
      ROS production was identified. Rotenone-induced apoptosis was inhibited by
      treatment with antioxidants (glutathione, N-acetylcysteine, and vitamin C). The
      role of rotenone-induced mitochondrial ROS in apoptosis was also confirmed by the
      finding that HT1080 cells overexpressing magnesium superoxide dismutase were more
      resistant to rotenone-induced apoptosis than control cells. These results suggest
      that rotenone is able to induce apoptosis via enhancing the amount of
      mitochondrial reactive oxygen species production.

PMID- 12496266
TI  - P2X7 receptor cell surface expression and cytolytic pore formation are regulated
      by a distal C-terminal region.
AB  - The importance of the cytosolic C-terminal region of the P2X7 receptor (P2X7R) is
      unquestioned, yet little is known about the functional domains of this region and
      how they may contribute to the numerous properties ascribed to this receptor. A
      structure-function analysis of truncated and single-residue-mutated P2X7
      receptors was performed in HEK-293 cells and Xenopus oocytes. Cells expressing
      receptors truncated at residue 581 (of 595) have negligible ethidium ion uptake,
      whereas those expressing the P2X7R truncated at position 582 give wild type
      ethidium ion uptake suggesting that pore formation requires over 95% of the C
      terminal tail. Channel function was evident even in receptors that were truncated
      at position 380 indicating that only a small portion of the cytosolic region is
      required for channel activity. Surprisingly, truncations in the region between
      residues 551 and 581 resulted in non-functional receptors with no detectable cell
      surface expression in HEK-293 cells. A more detailed analysis revealed that
      mutations of single residues within this region could also abolish receptor
      function and cell surface expression, suggesting that this region may participate
      in regulating the surface expression of the pore-forming P2X7R.

PMID- 12496267
TI  - Cholecystokinin stimulates extracellular signal-regulated kinase through
      activation of the epidermal growth factor receptor, Yes, and protein kinase C.
      Signal amplification at the level of Raf by activation of protein kinase
      Cepsilon.
AB  - Cholecystokinin (CCK) and related peptides are potent growth factors in the
      gastrointestinal tract and may be important for human cancer. CCK exerts its
      growth modulatory effects through G(q)-coupled receptors (CCK(A) and CCK(B)) and
      activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). In the
      present study, we investigated the different mechanisms participating in CCK
      induced activation of ERK1/2 in pancreatic AR42J cells expressing both CCK(A) and
      CCK(B). CCK activated ERK1/2 and Raf-1 to a similar extent as epidermal growth
      factor (EGF). Inhibition of EGF receptor (EGFR) tyrosine kinase or expression of
      dominant-negative Ras reduced CCK-induced ERK1/2 activation, indicating
      participation of the EGFR and Ras in CCK-induced ERK1/2 activation. However,
      compared with EGF, CCK caused only small increases in tyrosine phosphorylation of
      the EGFR and Shc, Shc-Grb2 complex formation, and Ras activation. Signal
      amplification between Ras and Raf in a CCK-induced ERK cascade appears to be
      mediated by activation of protein kinase Cepsilon (PKCepsilon), because 1) down
      modulation of phorbol ester-sensitive PKCs inhibited CCK-induced activation of
      Ras, Raf, and ERK1/2 without influencing Shc-Grb2 complex formation; 2)
      PKCepsilon, but not PKCalpha or PKCdelta, was detectable in Raf-1
      immunoprecipitates, although CCK activated all three PKC isoenzymes. In addition,
      the present study provides evidence that the Src family tyrosine kinase Yes is
      activated by CCK and mediates CCK-induced tyrosine phosphorylation of Shc.
      Furthermore, we show that CCK-induced activation of the EGFR and Yes is achieved
      through the CCK(B) receptor. Together, our data show that different signals
      emanating from the CCK receptors mediate ERK1/2 activation; activation of Yes and
      the EGFR mediate Shc-Grb2 recruitment, and activation of PKC, most likely
      PKCepsilon, augments CCK-stimulated ERK1/2 activation at the Ras/Raf level.

PMID- 12496268
TI  - Mechanism of calcium-independent synaptotagmin binding to target SNAREs.
AB  - Synaptic vesicle exocytosis requires three SNARE (soluble N-ethylmaleimide
      sensitive-factor attachment protein receptor) proteins: syntaxin and SNAP-25 on
      the plasma membrane (t-SNAREs) and synaptobrevin/VAMP on the synaptic vesicles (v
      SNARE). Vesicular synaptotagmin 1 is essential for fast synchronous SNARE
      mediated exocytosis and interacts with the SNAREs in brain material. To uncover
      the step at which synaptotagmin becomes linked to the three SNAREs, we purified
      all four proteins from brain membranes and analyzed their interactions. Our study
      reveals that, in the absence of calcium, native synaptotagmin 1 binds the t-SNARE
      heterodimer, formed from syntaxin and SNAP-25. This interaction is both
      stoichiometric and of high affinity. Synaptotagmin contains two divergent but
      conserved C2 domains that can act independently in calcium-triggered phospholipid
      binding. We now show that both C2 domains are strictly required for the calcium
      independent interaction with the t-SNARE heterodimer, indicating that the double
      C2 domain structure of synaptotagmin may have evolved to acquire a function
      beyond calcium/phospholipid binding.

PMID- 12496269
TI  - Analysis of the kinetics of prothrombin activation and evidence that two
      equilibrating forms of prothrombinase are involved in the process.
AB  - Prothrombinase cleaves prothrombin at Arg(271) and Arg(320) to produce thrombin.
      The kinetics of cleavage of five recombinant prothrombins were measured: wild
      type prothrombin (WT-II), R155A/R284A/R271A prothrombin (rMZ-II),
      R155A/R284A/R320A prothrombin (rP2-II), S525C prothrombin labeled with
      fluorescein (WT-II-F*), and R155A/R284A/R271A/S525C prothrombin labeled with
      fluorescein (rMZ-II-F*). rMZ-II and rP2-II are cleaved only at Arg(320) and
      Arg(271), respectively, to yield the intermediates meizothrombin and prethrombin
      2, respectively. WT-II-F* and rMZ-II-F* were labeled at Cys(525) with
      fluorescein; cleavage was monitored by enhanced fluorescence. Activation kinetics
      of WT-II, rMZ-II, and rP2-II indicated that the catalytic efficiency of cleavage
      at Arg(320) was increased by 30,000-fold by the cofactor factor Va, as was the
      conversion of prothrombin to thrombin. However, factor Va increased cleavage at
      Arg(271) only by 34-fold. Although WT-II competitively inhibited cleavage of WT
      II-F*, rMZ-II or rP2-II did not inhibit completely even at saturating
      concentrations. However, rMZ-II and rP2-II together inhibited WT-II-F* cleavage
      competitively. Both WT-II and rMZ-II competitively inhibited rMZ-II-F* cleavage,
      whereas rP2-II did not. A model of prothrombin activation that includes two
      equilibrating forms of prothrombinase, each recognizing one of the cleavage
      sites, is quantitatively consistent with all of the experimental observations.
      Therefore, we conclude that the kinetics of prothrombin activation can be
      described by a "ping-pong"-like mechanism.

PMID- 12496270
TI  - A Kunitz-type protease inhibitor, bikunin, inhibits ovarian cancer cell invasion
      by blocking the calcium-dependent transforming growth factor-beta 1 signaling
      cascade.
AB  - Bikunin is a Kunitz-type protease inhibitor, acting at the level of tumor
      invasion and metastasis. The goal of this study was to investigate the effect of
      bikunin-dependent signal transduction involved in the expression of a plasminogen
      activator (PA) system and invasion. We report here the following. 1) The human
      ovarian cancer cell line HRA produced secreted and cell-associated urokinase-type
      PA (uPA) and PA inhibitor type 1 (PAI-1). The plasma membrane of the cells showed
      enzymatically active uPA even in the presence of high level of PAI-1, as measured
      by zymography, Western blot, chromogenic assay, enzyme-linked immunosorbent
      assay, and Northern blot. 2) HRA cells leading to invasion are induced through up
      regulation of uPA expression. 3) HRA cells specifically released transforming
      growth factor-beta type 1 (TGF-beta1) participating in an autocrine/paracrine
      regulation of cell invasion. 4) Elimination of endogenous TGF-beta1 could induce
      change in uPA/PAI-1 expression, which could in turn modify the invasive behavior
      of the cells. 5) The constitutive expression of TGF-beta1 as well as up
      regulation of the PA system observed in HRA cells was inhibited by preinoculation
      of the cells with bikunin or calcium channel blocker SK&F 96365 but not with
      nifedipine or verapamil, with an IC(50) of approximately 100 nm for bikunin or
      approximately 30 microm for SK&F 96365, respectively, as measured by enzyme
      linked immunosorbent assay. Bikunin showed no additive effect on SK&F 96365
      mediated suppression of TGF-beta1 expression. 6) The ability of TGF-beta1 to
      elevate free intracellular Ca(2+), followed by activation of Src and ERK, was
      reduced by preincubation of the cells with bikunin. In conclusion, bikunin could
      inhibit the constitutive expression of TGF-beta1 and TGF-beta1-mediated, Src- and
      ERK-dependent, PA system signaling cascade, at least in part, through inhibition
      of a non-voltage-sensitive calcium channel.

PMID- 12496271
TI  - Cleavage, but not read-through, stimulation activity is responsible for three
      biologic functions of transcription elongation factor S-II.
AB  - Transcription elongation factor S-II stimulates cleavage of nascent transcripts
      generated by RNA polymerase II stalled at transcription arrest sites. In vitro
      experiments have shown that this action promotes RNA polymerase II to read
      through these transcription arrest sites. This S-II-mediated cleavage is thought
      to be necessary, but not sufficient, to promote read-through in the in vitro
      systems. Therefore, Saccharomyces cerevisiae strains expressing S-II mutant
      proteins with different in vitro activities were used to study both the cleavage
      and the read-through stimulation activities of S-II to determine which S-II
      functions are responsible for its biologic functions. Strains expressing mutant S
      II proteins active in both cleavage and read-through stimulation were as
      resistant as wild type strains to 6-azauracil and mycophenolic acid. 6-Azauracil
      also induced IMD2 gene expression in both these mutant strains and the wild type.
      Furthermore, strains having a genotype consisting of one of these S-II mutations
      and the spt4 null mutation grew as well as the spt4 null mutant at 37 degrees C,
      a restrictive temperature for a strain bearing double null mutations of spt4 and
      S-II. In contrast, strains bearing S-II mutations defective in both cleavage and
      read-through stimulation had phenotypes similar to those of an S-II null mutant.
      However, one strain expressing a mutant S-II protein active only in cleavage
      stimulation had a phenotype similar to that of the wild type strain. These
      results suggest that cleavage, but not read-through, stimulation activity is
      responsible for all three biologic functions of S-II (i.e. suppression of 6
      azauracil sensitivity, induction of the IMD2 gene, and suppression of temperature
      sensitivity of spt4 null mutant).

PMID- 12496272
TI  - Expression cloning and characterization of a novel glycosylphosphatidylinositol
      anchored high density lipoprotein-binding protein, GPI-HBP1.
AB  - By expression cloning using fluorescent-labeled high density lipoprotein (HDL),
      we isolated two clones that conferred the cell surface binding of HDL. Nucleotide
      sequence of the two clones revealed that one corresponds to scavenger receptor
      class B, type 1 (SRBI) and the other encoded a novel protein with 228 amino
      acids. The primary structure of the newly identified HDL-binding protein
      resembles GPI-anchored proteins consisting of an N-terminal signal sequence, an
      acidic region with a cluster of aspartate and glutamate residues, an Ly-6 motif
      highly conserved among the lymphocyte antigen family, and a C-terminal
      hydrophobic region. This newly identified HDL-binding protein designated GPI
      anchored HDL-binding protein 1 (GPI-HBP1), was susceptible to
      phosphatidylinositol-specific phospholipase C treatment and binds HDL with high
      affinity (calculated K(d) = 2-3 microg/ml). Similar to SRBI, GPI-HBP1 mediates
      selective lipid uptake but not the protein component of HDL. Among various
      ligands for SRBI, HDL was most preferentially bound to GPI-HBP1. In contrast to
      SRBI, GPI-HBP1 lacked HDL-dependent cholesterol efflux. The GPI-HBP1 transcripts
      were detected with the highest levels in heart and, to a much lesser extent, in
      lung and liver. In situ hybridization revealed the accumulation of GPI-HBP1
      transcripts in cardiac muscle cells, hepatic Kupffer cells and sinusoidal
      endothelium, and bronchial epithelium and alveolar macrophages in the lung.

PMID- 12496273
TI  - The DNA binding domain of the gene 2.5 single-stranded DNA-binding protein of
      bacteriophage T7.
AB  - Gene 2.5 of bacteriophage T7 encodes a single-stranded DNA-binding protein that
      is essential for viral survival. Its crystal structure reveals a conserved
      oligosaccharide/oligonucleotide binding fold predicted to interact with single
      stranded DNA. However, there is no experimental evidence to support this
      hypothesis. Recently, we reported a genetic screen for lethal mutations in gene
      2.5 that we are using to identify functional domains of the gene 2.5 protein.
      This screen uncovered a number of mutations that led to amino acid substitutions
      in the proposed DNA binding domain. Three variant proteins, gp2.5-Y158C, gp2.5
      K152E, and gp2.5-Y111C/Y158C, exhibit a decrease in binding affinity for
      oligonucleotides. A fourth, gp2.5-K109I, exhibits an altered mode of binding
      single-stranded DNA. A carboxyl-terminal truncation of gene 2.5 protein, gp2.5
      Delta26C, binds single-stranded DNA 10-fold more tightly than the wild-type
      protein. The three altered proteins defective in single-stranded DNA binding
      cannot mediate the annealing of homologous DNA, whereas gp2.5-Delta26C mediates
      the reaction more effectively than does wild-type. Gp2.5-K109I retains this
      annealing ability, albeit slightly less efficiently. With the exception of gp2.5
      Delta26C, all variant proteins form dimers in solution and physically interact
      with T7 DNA polymerase.

PMID- 12496274
TI  - Mutational and functional analysis of a segment of the sigma family bacteriophage
      T4 late promoter recognition protein gp55.
AB  - Bacteriophage T4 late promoters, which consist of a simple 8-base pair TATA box,
      are recognized by the gene 55 protein (gp55), a small, highly diverged member of
      the sigma family proteins that replaces sigma(70) during the final phase of the
      T4 multiplication cycle. A 16-amino acid segment of gp55 that is proposed to be
      homologous to the sigma(70) region 2.2 has been subjected to alanine scanning and
      other mutagenesis. The corresponding proteins have been examined in vitro for
      binding to Escherichia coli RNA polymerase core enzyme and for the ability to
      generate accurately initiating basal as well as sliding clamp-activated T4 late
      transcription. Mutations in the amino acid 68-83 segment of gp55 generate a wide
      range of effects on these functions. The changes are interpreted in terms of the
      multiple steps of involvement of gp55, like other sigma proteins, in
      transcription. Effects of mutations on RNA polymerase core binding are consistent
      with the previously proposed homology of amino acids 68-82 of gp55 with sigma(70)
      region 2.2 and the recently determined structures of the Thermus thermophilus and
      Thermus aquaticus sigma(70)-RNA polymerase holoenzymes.

PMID- 12496275
TI  - DNA-binding mechanism of O6-alkylguanine-DNA alkyltransferase. Effects of protein
      and DNA alkylation on complex stability.
AB  - The mutagenic and cytotoxic effects of many endogenous and exogenous alkylating
      agents are mitigated by the actions of O(6)-alkylguanine-DNA alkyltransferase
      (AGT). In humans this protein protects the integrity of the genome, but it also
      contributes to the resistance of tumors to DNA-alkylating chemotherapeutic
      agents. Here we report properties of the interaction between AGT and short DNA
      oligonucleotides. We show that although AGT sediments as a monomer in the absence
      of DNA, it binds cooperatively to both single-stranded and double-stranded
      deoxyribonucleotides. This strong cooperative interaction is only slightly
      perturbed by active site mutation of AGT or by alkylation of either AGT or DNA.
      The stoichiometry of complex formation with 16-mer oligonucleotides, assessed by
      analytical ultracentrifugation and electrophoretic mobility shift assays, is 4:1
      on single-stranded and duplex DNA and is unchanged by several active site
      mutations or by protein or DNA alkylation. These results have significant
      implications for the mechanisms by which AGT locates and interacts with
      repairable alkyl lesions to effect DNA repair.

PMID- 12496276
TI  - Identification of UNC119 as a novel activator of SRC-type tyrosine kinases.
AB  - Lyn, an Src-type tyrosine kinase, is associated with the interleukin (IL)-5
      receptor in eosinophils. The mechanism of its activation is unknown. Through
      yeast two-hybrid screening we have cloned and characterized a new signaling
      molecule, Unc119, that associates with IL-5Ralpha and Src family tyrosine
      kinases. Unc119 induces the catalytic activity of these kinases through
      interaction with Src homology 2 and 3 domains. IL-5 stimulation of eosinophils
      increases Unc119 association with Lyn and induces its catalytic activity. Lyn is
      important for eosinophil survival. Eosinophils that are transduced with Unc119
      have increased Lyn activity and demonstrate prolonged survival in the absence of
      IL-5. Inhibition of Unc119 down-regulates eosinophil survival. To our knowledge
      Unc119 is the first receptor-associated activator of Src family tyrosine kinases.

PMID- 12496277
TI  - Identification of gene-selective modulators of the bile acid receptor FXR.
AB  - BAR is a nuclear bile acid receptor (BAR) (FXR) receptor that regulates gene
      networks involved in cholesterol and bile acid homeostasis. We have identified
      two classes of synthetic compounds that differentially modulate BAR activity. The
      first class activates BAR target genes in the predicted fashion and is 25-fold
      more potent than endogenous bile acids. The second class, represented by AGN34,
      antagonizes BAR in transient reporter assays. Surprisingly, this compound acts in
      a gene-selective manner in vivo: it is an agonist on CYP7A1, an antagonist on
      IBABP, and is neutral on SHP. These findings indicate that synthetic BAR
      modulators can be developed to regulate transcription in a gene-specific fashion.
      Given the ability of BAR to regulate several lipid homeostatic pathways, the
      identification of gene-selective BAR modulators have important implications for
      the development of improved cholesterol lowering agents.

PMID- 12496278
TI  - Apoptin induces tumor-specific apoptosis as a globular multimer.
AB  - The chicken anemia virus-derived Apoptin protein induces tumor-specific
      apoptosis. Here, we show that recombinant Apoptin protein spontaneously forms non
      covalent globular aggregates comprising 30 to 40 subunits in vitro. This
      multimerization is robust and virtually irreversible, and the globular aggregates
      are also stable in cell extracts, suggesting that they remain intact within the
      cell. Furthermore, studies of Apoptin expressed in living cells confirm that
      Apoptin indeed exists in large complexes in vivo. We map the structural motifs
      responsible for multimerization in vitro and aggregation in vivo to the N
      terminal half of the protein. Moreover, we show that covalently fixing the
      Apoptin monomers within the recombinant protein multimer by internal cross
      linking does not affect the biological activity of Apoptin, as these fixed
      aggregates exhibit similar tumor-specific localization and apoptosis-inducing
      properties as non-cross-linked Apoptin. Taken together, our results imply that
      recombinant Apoptin protein is a multimer when inducing apoptosis, and we propose
      that this multimeric state is an essential feature of its ability to do so.
      Finally, we determine that Apoptin adopts little, if any, regular secondary
      structure within the aggregates. This surprising result would classify Apoptin as
      the first protein for which, rather than the formation of a well defined tertiary
      and quaternary structure, semi-random aggregation is sufficient for activity.

PMID- 12496279
TI  - Evidence that high telomerase activity may induce a senescent-like growth arrest
      in human fibroblasts.
AB  - Expression of the catalytic subunit of human telomerase (hTERT), in normal human
      fibroblasts allows them to escape replicative senescence. However, we have
      observed that populations of hTERT-immortalized human fibroblasts contain 3-20%
      cells with a senescent morphology. To determine what causes the appearance of
      these senescent-like cells, we used flow cytometry to select them from the
      population and analyzed them for various senescence markers, telomere length, and
      telomerase activity. This subpopulation of cells had elevated levels of p21 and
      hypophosphorylated Rb, but telomere length was similar to that of the immortal
      cells in the culture that was sorted. Surprisingly, telomerase activity in the
      senescent-like cells was significantly elevated compared with immortal cells from
      the same population, suggesting that high telomerase activity may induce the
      senescent phenotype. Furthermore, transfection of normal fibroblasts with a hTERT
      expressing plasmid that confers high telomerase activity led to the induction of
      p21, a higher percentage of SA-beta-galactosidase-positive cells, and a greater
      number of cells entering growth arrest compared with controls. These results
      suggest that excessive telomerase activity may act as a hyperproliferative signal
      in cells and induce a senescent phenotype in a manner similar to that seen
      following overexpression of oncogenic Ras, Raf, and E2F1. Thus, there must be a
      critical threshold of telomerase activity that permits cell proliferation.

PMID- 12496280
TI  - Protein-protein interactions within an E2-RING finger complex. Implications for
      ubiquitin-dependent DNA damage repair.
AB  - The RING finger protein RAD5 interacts and cooperates with the UBC13-MMS2
      ubiquitin-conjugating enzyme in postreplication DNA damage repair in yeast.
      Previous observations implied that the function of UBC13 and MMS2 is dependent on
      the presence of RAD5, suggesting that the RING finger protein might act as a
      ubiquitin-protein ligase specific for the UBC13-MMS2 complex. In support of this
      notion it is shown here that the contact surfaces between the RAD5 RING domain
      and UBC13 correspond to those found in other pairs of ubiquitin-conjugating
      enzymes and ubiquitin-protein ligases. Mutations that compromise the protein
      protein interactions either between the RING domain and UBC13 or within the UBC13
      MMS2 dimer were found to have variable effects on repair activity in vivo that
      strongly depended on the expression levels of the corresponding mutants.
      Quantitative analysis of the affinity and kinetics of the UBC13-MMS2 interaction
      suggests a highly dynamic association model in which compromised mutual
      interactions result in phenotypic effects only under conditions where protein
      levels become limiting. Finally, this study demonstrates that beyond its
      cooperation with the UBC13-MMS2 dimer, RAD5 must have an additional role in DNA
      damage repair independent of its RING finger domain.

PMID- 12496281
TI  - Chromophore environment provides clue to "kindling fluorescent protein" riddle.
AB  - asCP, the unique green fluorescent protein-like nonfluorescent chromoprotein from
      the sea anemone Anemonia sulcata, becomes fluorescent ("kindles") upon green
      light irradiation, with maximum emission at 595 nm. The kindled protein then
      relaxes to a nonfluorescent state or can be "quenched" instantly by blue light
      irradiation. In this work, we used asCP mutants to investigate the mechanism
      underlying kindling. Using site-directed mutagenesis we showed that amino acids
      spatially surrounding Tyr(66) in the chromophore are crucial for kindling. We
      propose a model of the kindling mechanism, in which the key event is chromophore
      turning or cis-trans isomerization. Using site-directed mutagenesis we also
      managed to transfer the kindling property to the two other coral chromoproteins.
      Remarkably, most kindling mutants were capable of both reversible and
      irreversible kindling. Also, we obtained novel variants that kindled upon blue
      light irradiation. The diversity of photoactivated fluorescent proteins that can
      be developed by site-directed mutagenesis is promising for biotechnological
      needs.

PMID- 12496282
TI  - A novel protein tightly bound to bacterial magnetic particles in Magnetospirillum
      magneticum strain AMB-1.
AB  - Magnetic bacteria synthesize magnetite crystals with species-dependent
      morphologies. The molecular mechanisms that control nano-sized magnetite crystal
      formation and the generation of diverse morphologies are not well understood.
      From the analysis of magnetite crystal-associated proteins, several low molecular
      mass proteins tightly bound to bacterial magnetite were obtained from
      Magnetospirillum magneticum strain AMB-1. These proteins showed common features
      in their amino acid sequences, which contain hydrophobic N-terminal and
      hydrophilic C-terminal regions. The C-terminal regions in Mms5, Mms6, Mms7, and
      Mms13 contain dense carboxyl and hydroxyl groups that bind iron ions. Nano-sized
      magnetic particles similar to those in magnetic bacteria were prepared by
      chemical synthesis of magnetite in the presence of the acidic protein Mms6. These
      proteins may be directly involved in biological magnetite crystal formation in
      magnetic bacteria.

PMID- 12496283
TI  - The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by
      propionate and other short chain carboxylic acids.
AB  - GPR41 and GPR43 are related members of a homologous family of orphan G protein
      coupled receptors that are tandemly encoded at a single chromosomal locus in both
      humans and mice. We identified the acetate anion as an agonist of human GPR43
      during routine ligand bank screening in yeast. This activity was confirmed after
      transient transfection of GPR43 into mammalian cells using Ca(2+) mobilization
      and [(35)S]guanosine 5'-O-(3-thiotriphosphate) binding assays and by coexpression
      with GIRK G protein-regulated potassium channels in Xenopus laevis oocytes. Other
      short chain carboxylic acid anions such as formate, propionate, butyrate, and
      pentanoate also had agonist activity. GPR41 is related to GPR43 (52% similarity;
      43% identity) and was activated by similar ligands but with differing specificity
      for carbon chain length, with pentanoate being the most potent agonist. A third
      family member, GPR42, is most likely a recent gene duplication of GPR41 and may
      be a pseudogene. GPR41 was expressed primarily in adipose tissue, whereas the
      highest levels of GPR43 were found in immune cells. The identity of the cognate
      physiological ligands for these receptors is not clear, although propionate is
      known to occur in vivo at high concentrations under certain pathophysiological
      conditions.

PMID- 12496284
TI  - The orphan G protein-coupled receptor GPR40 is activated by medium and long chain
      fatty acids.
AB  - GPR40 is a member of a subfamily of homologous G protein-coupled receptors that
      include GPR41 and GPR43 and that have no current function or ligand ascribed.
      Ligand fishing experiments in HEK293 cells expressing human GPR40 revealed that a
      range of saturated and unsaturated carboxylic acids with carbon chain lengths
      greater than six were able to induce an elevation of [Ca(2+)](i), measured using
      a fluorometric imaging plate reader. 5,8,11-Eicosatriynoic acid was the most
      potent fatty acid tested, with a pEC(50) of 5.7. G protein coupling of GPR40 was
      examined in Chinese hamster ovary cells expressing the G alpha(q/i)-responsive
      Gal4-Elk1 reporter system. Expression of human GPR40 led to a constitutive
      induction of luciferase activity, which was further increased by exposure of the
      cells to eicosatriynoic acid. Neither the constitutive nor ligand-mediated
      luciferase induction was inhibited by pertussis toxin treatment, suggesting that
      GPR40 was coupled to G alpha(q/11.) Expression analysis by quantitative reverse
      transcription-PCR showed that GPR40 was specifically expressed in brain and
      pancreas, with expression in rodent pancreas being localized to insulin-producing
      beta-cells. These data suggest that some of the physiological effects of fatty
      acids in pancreatic islets and brain may be mediated through a cell-surface
      receptor.

PMID- 12496285
TI  - Calcium/calmodulin-dependent protein kinase II regulation of c-FLIP expression
      and phosphorylation in modulation of Fas-mediated signaling in malignant glioma
      cells.
AB  - Fas, upon cross-linking with Fas ligand (FasL) or Fas agonistic antibody,
      transduces apoptotic yet also proliferative signals, which have been implicated
      in tumor pathogenesis. In this study, we investigated the molecular mechanisms
      that control Fas-mediated signaling in glioma cells. Fas agonistic antibody, CH
      11, induced apoptosis in sensitive glioma cells through caspase-8 recruitment to
      the Fas-mediated death-inducing signaling complex (DISC) where caspase-8 was
      cleaved to initiate apoptosis through a systematic cleavage of downstream
      substrates. In contrast, CH-11 stimulated cell growth in resistant glioma cells
      through recruitment of c-FLIP (cellular Fas-associated death domain (FADD)-like
      interleukin-1beta-converting enzyme (FLICE)-inhibitory protein) to the Fas
      mediated DISC. Three isoforms of long form c-FLIP were detected in glioma cells,
      but only the phosphorylated isoform was recruited to and cleaved into a p43
      intermediate form in the Fas-mediated DISC in resistant cells. Calcium/calmodulin
      dependent protein kinase II (CaMK II) activity was up-regulated in resistant
      cells. Treatment of resistant cells with the CaMK II inhibitor KN-93 inhibited
      CaMK II activity, reduced c-FLIP expression, inhibited c-FLIP phosphorylation,
      and rescued CH-11 sensitivity. Transfection of CaMK II cDNA in sensitive cells
      rendered them resistant to CH-11. These results indicated that CaMK II regulates
      c-FLIP expression and phosphorylation, thus modulating Fas-mediated signaling in
      glioma cells.

PMID- 12496286
TI  - Contribution of the Atm protein to maintaining cellular homeostasis evidenced by
      continuous activation of the AP-1 pathway in Atm-deficient brains.
AB  - Maintenance of genome stability is essential for keeping cellular homeostasis.
      The DNA damage response is a central component in maintaining genome integrity.
      Among of the most cytotoxic DNA lesions are double strand breaks (DSBs) caused by
      ionizing radiation or radiomimetic chemicals. ATM is missing or inactivated in
      patients with ataxia-telangiectasia. Ataxia-telangiectasia patients display a
      pleiotropic phenotype and suffer primarily from progressive ataxia caused by
      degeneration of cerebellar Purkinje and granule neurons. Additional features are
      immunodeficiency, genomic instability, radiation sensitivity, and cancer
      predisposition. Disruption of the mouse Atm locus creates a murine model of
      ataxia-telangiectasia that exhibits most of the clinical features of the human
      disease but very mild neuronal abnormality. The ATM protein is a multifunctional
      protein kinase, which serves as a master regulator of cellular responses to DSBs.
      There is growing evidence that ATM may be involved in addition to the DSB
      response in other processes that maintain processes in cellular homeostasis. For
      example, mounting evidence points to increased oxidative stress in the absence of
      ATM. Here we report that the AP-1 pathway is constantly active in the brains of
      Atm-deficient mice not treated with DNA damaging agents. A canonical activation
      (increased phosphorylation of mitogen-activated protein kinase kinase-4, c-Jun N
      terminal kinase, and c-Jun) of the AP-1 pathway was found in Atm-deficient
      cerebra, whereas induction of the AP-1 pathway in Atm-deficient cerebella is
      likely to mediate elevated expression of c-Fos and c-Jun. Although Atm(+/+) mice
      are capable of responding to ionizing radiation by activating stress responses
      such as the AP-1 pathway, Atm-deficient mice display higher basal AP-1 activity
      but gradually lose their ability to activate AP-1 DNA-binding activity in
      response to ionizing radiation. Our results further demonstrate that inactivation
      of the ATM gene results in a state of constant stress.

PMID- 12496287
TI  - Studies with novel Pdr5p substrates demonstrate a strong size dependence for
      xenobiotic efflux.
AB  - The yeast (Saccharomyces cerevisiae) multidrug transporter Pdr5p effluxes a broad
      range of substrates that are variable in structure and mode of action. Previous
      work suggested that molecular size and ionization could be important parameters.
      In this study, we compared the relative sensitivity of isogenic PDR5 and pdr5
      strains toward putative substrates that are similar in chemical structure. Three
      series were used: imidazole-containing compounds, trialkyltin chlorides, and
      tetraalkyltin compounds. We demonstrate that the Pdr5p transporter is capable of
      mediating transport of substrates that neither ionize nor have electron pair
      donors and that are much simpler in structure than those transported by the human
      MDR1-encoded P-glycoprotein. Furthermore, the size of the substrate is critical
      and independent of any requirement for hydrophobicity. Substrates have surface
      volumes greater than 90 A(3) with an optimum response at approximately 200-225
      A(3) as determined by molecular modeling. Assays measuring the efflux from cells
      of [(3)H]chloramphenicol and [(3)H]tritylimidazole were used. A concentration
      dependent inhibition of chloramphenicol transport was observed with imidazole
      derivatives but not with either the organotin compounds or the antitumor agent
      doxorubicin. In contrast, several of the organotin compounds were potent
      inhibitors of tritylimidazole efflux, but the Pdr5p substrate tetrapropyltin was
      ineffective in both assays. This argues for the existence of at least three
      substrate-binding sites on Pdr5p that differ in behavior from those of the
      mammalian P-glycoprotein. Evidence also indicates that some substrates are
      capable of interacting at more than one site. The surprising observation that
      Pdr5p mediates resistance to tetraalkyltins suggests that one of the sites might
      use only hydrophobic interactions to bind substrates.

PMID- 12496288
TI  - Identification of bioactive molecules by adipogenesis profiling of organic
      compounds.
AB  - An important step in the postgenomic drug discovery is the construction of high
      quality chemical libraries that generate bioactive molecules at high rates. Here
      we report a cell-based approach to composing a focused library of biologically
      active compounds. A collection of bioactive non-cytotoxic chemicals was
      identified from a divergent library through the effects on the insulin-induced
      adipogenesis of 3T3-L1 cells, one of the most drastic and sensitive morphological
      alterations in cultured mammalian cells. The resulting focused library amply
      contained unique compounds with a broad range of pharmacological effects,
      including glucose-uptake enhancement, cytokine inhibition, osteogenesis
      stimulation, and selective suppression of cancer cells. Adipogenesis profiling of
      organic compounds generates a focused chemical library for multiple biological
      effects that are seemingly unrelated to adipogenesis, just as genetic screens
      with the morphology of fly eyes identify oncogenes and neurodegenerative genes.

PMID- 12496289
TI  - Down-regulation of voltage-gated Ca2+ channels by neuronal calcium sensor-1 is
      beta subunit-specific.
AB  - Neuronal Ca(2+) sensor protein-1 (NCS-1) is a member of the Ca(2+) binding
      protein family, with three functional Ca(2+) binding EF-hands and an N-terminal
      myristoylation site. NCS-1 is expressed in brain and heart during embryonic and
      postnatal development. In neurons, NCS-1 facilitates neurotransmitter release,
      but both inhibition and facilitation of the Ca(2+) current amplitude have been
      reported. In heart, NCS-1 co-immunoprecipitates with K(+) channels and modulates
      their activity, but the potential effects of NCS-1 on cardiac Ca(2+) channels
      have not been investigated. To directly assess the effect of NCS-1 on the various
      types of Ca(2+) channels we have co-expressed NCS-1 in Xenopus oocytes, with
      Ca(V)1.2, Ca(V)2.1, and Ca(V)2.2 Ca(2+) channels, using various subunit
      combinations. The major effect of NCS-1 was to decrease Ca(2+) current amplitude,
      recorded with the three different types of alpha(1) subunit. When expressed with
      Ca(V)2.1, the depression of Ca(2+) current amplitude induced by NCS-1 was
      dependent upon the identity of the beta subunit expressed, with no block recorded
      without beta subunit or with the beta(3) subunit. Current-voltage and
      inactivation curves were also slightly modified and displayed a different
      specificity toward the beta subunits. Taken together, these data suggest that NCS
      1 is able to modulate cardiac and neuronal voltage-gated Ca(2+) channels in a
      beta subunit specific manner.

PMID- 12496290
TI  - R-Ras glucosylation and transient RhoA activation determine the cytopathic effect
      produced by toxin B variants from toxin A-negative strains of Clostridium
      difficile.
AB  - Clostridium difficile induces antibiotic-associated diarrhea through the
      production of toxin A and toxin B; the former toxin has been assumed to be
      responsible for the symptoms of the disease. Several toxin A-negative strains
      from C. difficile have recently been isolated from clinical cases and have been
      reported to produce toxin B variants eliciting an atypical cytopathic effect.
      Ultrastructural analysis indicated these toxins induce a rounding cytopathic
      effect and filopodia-like structures. Toxin B variants glucosylated R-Ras, and
      transfection with a constitutively active mutant of this GTPase protected cells
      against their cytopathic effect. Treatment of cells with toxin B variants induced
      detachment from the extracellular matrix and blockade of the epidermal growth
      factor-mediated phosphorylation of extracellular-regulated protein kinases,
      demonstrating a deleterious effect on the R-Ras-controlled avidity of integrins.
      Treatment with toxin B variants also induced a transient activation of RhoA
      probably because of inactivation of Rac1. Altogether, these data indicate that
      the cytopathic effect induced by toxin B variants is because of cell rounding and
      detachment mediated by R-Ras glucosylation, and the induction of filopodia-like
      structures is mediated by RhoA activation. Implications for the pathophysiology
      of C. difficile-induced diarrhea are discussed.

PMID- 12496291
TI  - Val200 residue in Lys189-Lys205 outermost loop on the A domain of sarcoplasmic
      reticulum Ca2+-ATPase is critical for rapid processing of phosphoenzyme
      intermediate after loss of ADP sensitivity.
AB  - Possible roles of the Lys(189)-Lys(205) outermost loop on the A domain of
      sarcoplasmic reticulum Ca(2+)-ATPase were explored by mutagenesis. Both
      nonconservative and conservative substitutions of Val(200) caused very strong
      inhibition of Ca(2+)-ATPase activity, whereas substitutions of other residues on
      this loop reduced activity only moderately. All of the Val(200) mutants formed
      phosphoenzyme intermediate (EP) from ATP. Isomerization from ADP-sensitive EP
      (E1P) to ADP-insensitive EP (E2P) was not inhibited in the mutants, and a
      substantially larger amount of E2P actually accumulated in the mutants than in
      wild-type sarcoplasmic reticulum Ca(2+)-ATPase at steady state. In contrast,
      decay of EP formed from ATP in the presence of Ca(2+) was strongly inhibited in
      the mutants. Hydrolysis of E2P formed from P(i) in the absence of Ca(2+) was also
      strongly inhibited but was faster than the decay of EP formed from ATP,
      indicating that the main kinetic limitation of the decay comes after loss of ADP
      sensitivity but before E2P hydrolysis. On the basis of the well accepted
      mechanism of the Ca(2+)-ATPase, the limitation is likely associated with the
      Ca(2+)-releasing step from E2P.Ca(2). On the other hand, the rate of activation
      of dephosphorylated enzyme on high affinity Ca(2+) binding was not altered by the
      substitutions. In light of the crystal structures, the present results strongly
      suggest that Val(200) confers appropriate interactions of the Lys(189)-Lys(205)
      loop with the P domain in the Ca(2+)-released form of E2P. Results further
      suggest that these interactions, however, do not contribute much to domain
      organization in the dephosphorylated enzyme and thus would be mostly lost on E2P
      hydrolysis.

PMID- 12496292
TI  - Domain analysis of the Saccharomyces cerevisiae heterogeneous nuclear
      ribonucleoprotein, Nab2p. Dissecting the requirements for Nab2p-facilitated
      poly(A) RNA export.
AB  - Mature poly(A) RNA transcripts are exported from the nucleus in complex with
      heterogeneous nuclear ribonucleoproteins (hnRNPs). Nab2p is an essential
      Saccharomyces cerevisiae hnRNP protein that interacts with poly(A) RNA and
      shuttles between the nucleus and cytoplasm. Functional Nab2p is required for
      export of poly(A) RNA from the nucleus. The Nab2 protein consists of the
      following four domains: a unique N-terminal domain, a glutamine-rich domain, an
      arginine-glycine (RGG) domain, and a zinc finger domain. We generated Nab2p
      deletion mutants to analyze the contribution of each domain to the in vivo
      function of Nab2p. We first tested whether the deletion mutants could replace the
      essential NAB2 gene. We then examined the impact of these mutations on Nab2p
      localization, poly(A) RNA localization, and association of Nab2p with poly(A)
      RNA. Our analyses revealed that the N-terminal domain is required for nuclear
      export of both poly(A) RNA and Nab2p. We confirm that the RGG domain is important
      for Nab2p import in vivo. Finally, the zinc finger domain is critical for the
      interaction between Nab2p and poly(A) RNA in vivo. Our data support a model where
      Nab2p associates with poly(A) RNA in the nucleus through the zinc finger domain
      and facilitates the export of the poly(A) RNA through protein interactions
      mediated by the N-terminal domain.

PMID- 12496293
TI  - Involvement of a Na+/HCO-3 cotransporter in mouse sperm capacitation.
AB  - Mammalian sperm are incapable of fertilizing eggs immediately after ejaculation;
      they acquire fertilization capacity after residing in the female tract for a
      finite period of time. The physiological changes sperm undergo in the female
      reproductive tract that render sperm able to fertilize constitute the phenomenon
      of "sperm capacitation." We have demonstrated that capacitation is associated
      with an increase in the tyrosine phosphorylation of a subset of proteins and that
      these events are regulated by an HCO(3)(-)/cAMP-dependent pathway involving
      protein kinase A. Capacitation is also accompanied by hyperpolarization of the
      sperm plasma membrane. Here we present evidence that, in addition to its role in
      the regulation of adenylyl cyclase, HCO(3)(-) has a role in the regulation of
      plasma membrane potential in mouse sperm. Addition of HCO(3)(-) but not Cl(-)
      induces a hyperpolarizing current in mouse sperm plasma membranes. This HCO(3)(-)
      dependent hyperpolarization was not observed when Na(+) was replaced by the non
      permeant cation choline(+). Replacement of Na(+) by choline(+) also inhibited the
      capacitation-associated increase in protein tyrosine phosphorylation as well as
      the zona pellucida-induced acrosome reaction. The lack of an increase in protein
      tyrosine phosphorylation was overcome by the presence of cAMP agonists in the
      incubation medium. The lack of a hyperpolarizing HCO(3)(-) current and the
      inhibition of the capacitation-dependent increase in protein tyrosine
      phosphorylation in the absence of Na(+) suggest that a Na(+)/HCO(3)(-)
      cotransporter is present in mouse sperm and is coupled to events regulating
      capacitation.

PMID- 12496294
TI  - The fourth transmembrane segment forms the interface of the dopamine D2 receptor
      homodimer.
AB  - Considerable evidence suggests that G-protein-coupled receptors form homomeric
      and heteromeric dimers in vivo. Unraveling the structural mechanism for cross
      talk between receptors in a dimeric complex must start with the identification of
      the presently unknown dimer interface. Here, by using cysteine cross-linking, we
      identify the fourth transmembrane segment (TM4) as a symmetrical dimer interface
      in the dopamine D2 receptor. Cross-linking is unaffected by ligand binding, and
      ligand binding and receptor activation are unaffected by cross-linking,
      suggesting that the receptor is a constitutive dimer. The accessibility of
      adjacent residues in TM4, however, is affected by ligand binding, implying that
      the interface has functional significance.

PMID- 12496295
TI  - Why do divalent metal ions either promote or inhibit enzymatic reactions? The
      case of BamHI restriction endonuclease from combined quantum-classical
      simulations.
AB  - Divalent metal ions are essential to many enzymatic reactions involving nucleic
      acids, but their critical and specific role still needs to be uncovered.
      Restriction endonucleases are a prominent group of such metal-requiring enzymes.
      Large scale accurate simulations of Mg- and Ca-BamHI elucidate the mechanism of
      the catalytic reaction leading to DNA cleavage and show that it involves the
      concerted action of two metal ions and water molecules. It is also established
      that what is decisive for the dramatically different behavior of magnesium (a
      cocatalyst) and calcium (an inhibitor) are kinetic factors and not the properties
      of the prereactive states of the enzymes. A new perspective is opened for the
      understanding of the functional role of metal ions in biological processes.

PMID- 12496296
TI  - The impact of stereotype threat on age differences in memory performance.
AB  - This study investigated the hypothesis that age differences in memory performance
      may be influenced by stereotype threat associated with negative cultural beliefs
      about the impact of aging on memory. Recall was examined in 48 young and 48 older
      adults under conditions varying in the degree of induced threat. Conditions that
      maximize threat resulted in lower performance in older adults relative to both
      younger adults and to older adults who did not experience threat. The degree to
      which threat affected older adults' performance increased along with the value
      that these individuals placed on their memory ability. Older adults' memory
      performance across experimental conditions was observed to covary with degree of
      activation of the negative aging stereotype, providing support for the
      hypothesized relationship between stereotype activation and performance. Finally,
      stereotype threat also influenced mnemonic strategy use, which in turn partially
      mediated the impact of threat on recall. These results emphasize the important
      role played by contextual factors in determining age differences in memory
      performance.

PMID- 12496297
TI  - Use of memory compensation strategies is related to psychosocial and health
      indicators.
AB  - Research has shown that psychosocial and health characteristics may affect older
      adults' cognitive performance, self-referent beliefs, and general adaptive
      resilience. Are such characteristics related specifically to older adults'
      reported efforts to compensate for memory losses? The Memory Compensation
      Questionnaire (MCQ) measures 5 mechanisms of everyday memory compensation as well
      as 2 general aspects of compensatory motivation and awareness. Correlates were
      derived from indicators of specific health conditions, subjective health ratings,
      personality, well-being, and memory self-efficacy (MSE). All measures were
      administered to a cross-sectional sample of 528 healthy older adults between 55
      and 94 years of age from the Victoria Longitudinal Study. Specific health
      composites (i.e., infirmities, respiratory illness), several personality
      dimensions (e.g., agreeableness, neuroticism), negative affect, and low MSE were
      associated with more frequent use of everyday memory compensation strategies.
      Linking healthy older adults' cognitive resilience with individual
      characteristics is an important contribution to emerging conceptions of
      adaptation and success in late life.

PMID- 12496298
TI  - Discrete emotions in later life.
AB  - More positivity than negativity is demonstrated in this analysis of discrete
      emotions among 353 community-dwelling individuals from 72 to 99 years old. A
      complexity in positive emotions was displayed, with more happiness, contentment,
      and gratitude reported than frustration, sadness, and anger. Our results also
      imply that another individual's presence may elicit negative emotions such as
      anger and guilt, whereas perceptions of support may elicit various positive
      emotions. As expected, certain negative emotions were associated with poor
      health, with a link between sadness and sickness being most prominent. Of note,
      poor health did not undermine positive emotions. These findings provide an
      optimistic view of emotions in later life, even among individuals who are poor,
      not well educated, and/or physically unwell.

PMID- 12496299
TI  - The role of perceived control in the process of older peoples' recovery of
      physical functions after fall-related injuries: a prospective study.
AB  - This study examined the predictive role of perceived control in recovery of
      physical functions after fall-related injuries in a cohort of 165 older people
      who had completed preinjury baseline assessments including physical functioning
      and perceived control. Follow-up assessments of functioning were made at 8 weeks,
      5 months, and 12 months. Indicators for perceived control were mastery and self
      efficacy expectations. Physical functioning referred to self-reported
      difficulties with activities of daily living. Covariates included age, gender,
      level of education, preinjury health status, preinjury levels of social support
      and disability, and, additionally, the severity of the injury. Separate
      regression equations were estimated with disability as outcome at 8 weeks, 5
      months, and 12 months post injury. Although significant at 8 weeks and borderline
      significant at 5 months post injury, the predictive role of perceived control
      appeared to be comparatively small. Preinjury levels of disability were highly
      predictive for disability at 8 weeks, 5 months, and 12 months post injury. The
      severity of the injury is the predominant contributor to disability in the short
      term but becomes insignificant over time, whereas the influence of age on
      recovery becomes important after 5 months.

PMID- 12496300
TI  - Written language clues to cognitive changes of aging: an analysis of the letters
      of King James VI/I.
AB  - Reductions in language complexity normally occur in older adults because of
      decreased working memory and rate of language processing. Comparative measures
      can reveal whether linguistic change is due to normal aging or dementia.
      Linguistic analysis of a series of letters of King James, 1566-1625, investigate
      whether he exhibited a normative or atypical pattern of change. Fifty-seven
      letters from the years 1604 to 1624 were analyzed. Data modeling reveals a
      quadratic pattern of decline in written language complexity with increased
      diversity of vocabulary corresponding to historical reports of illness around
      1618-1619. This investigation demonstrates how language analysis can provide
      valuable insight to normal and pathological cognitive changes of aging as well as
      to the understanding of historical figures.

PMID- 12496301
TI  - Attentional abilities and functional outcomes following stroke.
AB  - Although stroke affects cognitive functioning as well as motor functioning,
      research on cognitive consequences has lagged behind that focused on motor
      function. The evidence that is accruing suggests that cognitive function is
      importantly related to successful rehabilitation. The present study examined two
      aspects of attentional functioning (divided attention and switching attention) in
      older adult stroke survivors and healthy older adults. In addition, the authors
      investigated the relation between attention and functional outcomes following
      stroke. Results revealed stroke-related deficits in both of the types of
      attention as well as significant associations between attentional functioning and
      both physical and social outcome measures. Poorer attentional performance was
      associated with a more negative impact of stroke on daily functioning. These
      findings suggest an important role for attention in post-stroke function and
      provide information that can contribute to improving outcomes following stroke.

PMID- 12496302
TI  - The impact of acuity on performance of four clinical measures of contrast
      sensitivity in Alzheimer's disease.
AB  - Investigations of contrast sensitivity losses in Alzheimer's disease (AD) have
      yielded mixed findings, with some investigators reporting deficits and others
      not. Potential reasons for these discrepancies include differences between
      samples and assessments utilized and the failure of some investigators to account
      for acuity differences between groups. To investigate these issues, we
      administered four clinical contrast sensitivity assessments to the same group of
      AD patients and elderly control participants and examined the impact of acuity on
      performance for each assessment. Results revealed group differences across the
      spatial frequency range. Further, group acuity differences significantly affected
      performance on two of the four measures (the Regan and the Vistech but not on the
      Pelli-Robson or Freiburg assessments). Information regarding the availability of
      established age norms, test-retest reliability data, and other factors including
      the time, cost, and training needed to administer each measure is provided to aid
      clinicians and researchers in their search for an effective measure of contrast
      sensitivity.

PMID- 12496303
TI  - Longevity and health care expenditures: the real reasons older people spend more.
AB  - OBJECTIVES: In this study, we investigated the relative contributions of both age
      and time to death to health care expenditures for elderly Medicare beneficiaries.
      We also analyzed differences in expenditure patterns by age and time to death for
      various service types and payers. METHODS: We conducted graphical analysis of
      person-month level data on 25,994 elderly persons from the 1992-1998 Medicare
      Current Beneficiary Survey Cost and Use files. RESULTS: Monthly health care
      expenditures for elderly people increase substantially with age primarily because
      mortality rates increase with age and health care expenditures increase with
      closeness to death. Time to death is the main reason for higher inpatient care
      expenditures, whereas aging is the main reason for higher long-term care
      expenditure. DISCUSSION: Both increases in the absolute number of elderly persons
      and in their longevity will increase future Medicare expenditures. Yet, the
      expected increase in per person health care expenditures caused by greater
      longevity of Medicare beneficiaries will be less than expected because of the
      concentration of expenditures at the end of life rather than during extra years
      of a relatively healthy life. The latter conclusion may be altered, however,
      because of other underlying considerations, such as technological change.

PMID- 12496304
TI  - Competing risk of household expansion or institutionalization in late life.
AB  - OBJECTIVES: The purpose of this study was to evaluate predictors of change in
      household size and institutionalization in late life. METHODS: The Duke
      Established Populations for Epidemiologic Studies of the Elderly cohort (n =
      3730) was assessed annually (1986-1996). Independent variables included home
      ownership, income, cognitive and functional ability, chronic illness, mood,
      household size, social support, and stressful life events. Competing risk of
      household expansion or institutionalization was modeled using (a) hazard of
      either event and (b) odds of household expansion or institutionalization among
      elders who experienced an event. RESULTS: Hazard of either event was associated
      with younger age, Black race, lower income, cognitive problems and stability,
      functional abilities and deterioration, low chronic illness burden, being
      unmarried, having more living children, and recent life events. Among those who
      reported either event, odds of institutionalization (vs. household expansion)
      were associated with older age, White race, cognitive and functional problems,
      high chronic illness burden, being married, having fewer living children, smaller
      household size, social isolation, and exits of nonspouse coresidents. DISCUSSION:
      Modeling separate effects of whether there was a household expansion or
      institutionalization, and if so, which type of event occurred, and taking into
      account acute and evolving states, enabled more precise understanding of the
      complex mechanisms involved in determining continued community residence or
      institutionalization.

PMID- 12496305
TI  - Religion and cognitive dysfunction in an elderly cohort.
AB  - OBJECTIVES: This study examines whether attendance at religious services has an
      inverse association with cognitive dysfunction in an elderly cohort in whom it
      has already been shown that religious attendance has an inverse association with
      physical disability and that social engagement has an inverse association with
      cognitive decline. METHODS: The study population is a racially and religiously
      diverse sample of 2,812 community-dwelling men and women from New Haven,
      Connecticut; it was representative of New Haven in 1982, but not of the United
      States then or now. The primary study hypothesis proposes that attendance at
      religious services as measured in 1982 contributes to the prediction of lower
      levels of cognitive dysfunction in 1985 and 1988. A multivariate logistic
      regression analysis controlling for seven sociodemographic, four behavioral, and
      seven biomedical covariables is conducted. RESULTS: Study results show an inverse
      association between religious attendance in 1982 and cognitive dysfunction in
      1985 (odds ratio = 0.64; 95% confidence interval = 0.49, 0.85). Religious
      attendance as measured in 1982 no longer contributes to the prediction of
      cognitive dysfunction in 1988. DISCUSSION: The short-term nature of the effect is
      partially explained by differential mortality. Persons with infrequent religious
      service attendance and with high levels of cognitive dysfunction in 1982 were
      more likely to die in the period from 1985 to 1988.

PMID- 12496306
TI  - Impact of husbands' involuntary job loss on wives' mental health, among older
      adults.
AB  - OBJECTIVES: This study estimates the consequences of older husbands' involuntary
      job loss for their wives' mental health. METHODS: Using longitudinal data from
      the 1992, 1994, and 1996 waves of the Health and Retirement Study, multivariate
      regression models were estimated to measure the impact of older husbands'
      involuntary job loss on wives' mental health. We created two longitudinal data
      sets of two waves each to use in our analysis. The first data set, or period,
      combined Waves 1 and 2 of the Health and Retirement Study and described the 1992
      1994 experience of spouse pairs in our sample. It included the wives of 55
      husbands who experienced involuntary job loss between these survey dates and a
      comparison group of wives of 730 continuously employed husbands. The second data
      set described the 1994-1996 experience of couples. In particular, it included the
      wives of an additional 38 husbands who were displaced from their jobs between
      Waves 2 and 3, and a comparison group of wives of 425 husbands who were
      continuously employed from 1994 to 1996. RESULTS: Husbands' involuntary job loss
      did not have a statistically significant effect on wives' mental health. We found
      no evidence that changes in husbands' depressive symptoms modified the effect of
      his job loss on wives' mental health. In the first period only, the effect of
      husbands' job loss on wives' mental health was more pronounced for wives who were
      more financially satisfied at baseline. DISCUSSION: There is limited evidence
      among this cohort that husbands' job loss increases wives' subsequent depressive
      symptoms. However, the effect of husbands' job loss on wives' mental health
      appears to be magnified when wives report being financially satisfied pre-job
      loss. This suggests that, for subgroups of older couples, mental health services
      specifically targeted at displaced men should also be made available to wives.

PMID- 12496307
TI  - Cognitive function and acute care utilization.
AB  - OBJECTIVES: Little is known about variation in cognitive function across the aged
      population, or how use and costs of health care vary with cognitive impairment.
      This study was designed to create a typology of cognitive function in a
      nationally representative sample, and evaluate acute care use in relation to
      cognitive function, holding constant confounding factors. By including proxy
      assessments of cognitive function, this is the first study to include individuals
      unable to respond themselves. METHODS: We analyzed the baseline year of the Asset
      and Health Dynamics Among the Oldest Old (AHEAD) survey, sponsored by the
      National Institute on Aging, to create three levels of cognitive function, using
      direct measures for self-respondents (n = 6,651) and proxy evaluations for the
      others (n = 792). We used a two-part model to predict the likelihood of using
      various health services and to evaluate intensity of care among users. RESULTS:
      Sixteen percent, 64%, and 20% of the sample fell into the low, moderate, and high
      cognitive function groups, respectively, that differed significantly on almost
      all demographic and health status measures, and some utilization measures.
      Controlling for other health and functional status measures, lower cognitive
      function had a significant and negative effect on outpatient services, but did
      not affect hospital use directly. DISCUSSION: Lower cognitive function may be a
      barrier to outpatient care, but these analyses should be repeated using
      administrative use and cost data.

PMID- 12496308
TI  - Effects of emotion-oriented care on work-related outcomes of professional
      caregivers in homes for elderly persons.
AB  - OBJECTIVES: A randomized controlled trial was conducted on the effects of emotion
      oriented care on professional caregivers in homes for elderly persons. Emotion
      oriented care is used in the care for cognitively impaired elderly persons and is
      mainly based on the validation approach. METHODS: Sixteen homes for the aged were
      randomly allocated to an intervention or control group. Three hundred
      professional caregivers were included in the study. The eight intervention homes
      received a training program in emotion-oriented care. In the eight control homes,
      usual care was continued. Measurements about job satisfaction, burnout, and sick
      leave were performed at baseline and after 3, 6, and 12 months of follow-up.
      RESULTS: Modest positive effects were found in favor of the intervention group.
      These related to various aspects of job satisfaction and burnout. The effects
      were not very consistent over time. No differences in sick leave were found.
      DISCUSSION: From this study, as well as other studies in this field, no strong
      effects were found of emotion-oriented care on work-related outcomes in
      professional caregivers. Additional research is therefore needed. In these new
      studies, special attention should be given to the optimization of the
      implementation process of emotion-oriented care programs.

PMID- 12496309
TI  - Efficacy of a psychoeducative group program for caregivers of demented persons
      living at home: a randomized controlled trial.
AB  - OBJECTIVES: To test the efficacy of a psychoeducative group program for informal
      caregivers of persons with dementia. METHODS: The study was a multicenter
      randomized controlled trial. Randomization was stratified according to sex and
      kinship. Participants randomized to the control group were referred to the
      traditional support groups. Participants in the study group had fifteen 2-hr
      weekly sessions focusing on stress appraisal and coping. Eligible participants
      (primary caregivers of community-dwelling persons with dementia) were blindly
      assessed before the randomization and after 16 weeks on the following measures:
      frequency and reactions to behavioral problems (primary outcome), burden,
      psychological distress, anxiety, perceived social support, and personal efficacy.
      RESULTS: A total of 158 participants were randomized to the study (n = 79) and
      control (n = 79) groups in 12 successive waves. Results show that study
      participants presented a 14% decrease in their reactions to the behavioral
      problems of the care-receivers as opposed to a 5% decrease in the control group (
      p =.04). The frequency of behavior problems also decreased ( p =.06), as did the
      cross-product frequency/reaction ( p =.02). There was no significant effect on
      the secondary outcome variables. DISCUSSION: This is one of the first studies
      showing a significant effect of this type of support group program on the
      caregivers of participants with dementia.

PMID- 12496310
TI  - Manganese specificity determinants in the Arabidopsis metal/H+ antiporter CAX2.
AB  - In plants and fungi, vacuolar transporters help remove potentially toxic cations
      from the cytosol. Metal/H(+) antiporters are involved in metal sequestration into
      the vacuole. However, the specific transport properties and the ability to
      manipulate these transporters to alter substrate specificity are poorly
      understood. The Arabidopsis thaliana cation exchangers, CAX1 and CAX2, can both
      transport Ca(2+) into the vacuole. There are 11 CAX-like transporters in
      Arabidopsis; however, CAX2 was the only characterized CAX transporter capable of
      vacuolar Mn(2+) transport when expressed in yeast. To determine the domains
      within CAX2 that mediate Mn(2+) specificity, six CAX2 mutants were constructed
      that contained different regions of the CAX1 transporter. One class displayed no
      alterations in Mn(2+) or Ca(2+) transport, the second class showed a reduction in
      Ca(2+) transport and no measurable Mn(2+) transport, and the third mutant, which
      contained a 10-amino acid domain from CAX1 (CAX2-C), showed no reduction in
      Ca(2+) transport and a complete loss of Mn(2+) transport. The subdomain analysis
      of CAX2-C identified a 3-amino acid region that is responsible for Mn(2+)
      specificity of CAX2. This study provides evidence for the feasibility of altering
      substrate specificity in a metal/H(+) antiporter, an important family of
      transporters found in a variety of organisms.

PMID- 12496311
TI  - Modulation of the trafficking efficiency and functional properties of ATP
      sensitive potassium channels through a single amino acid in the sulfonylurea
      receptor.
AB  - Mutations in the sulfonylurea receptor 1 (SUR1), a subunit of ATP-sensitive
      potassium (K(ATP)) channels, cause familial hyperinsulinism. One such mutation,
      deletion of phenylalanine 1388 (DeltaPhe-1388), leads to defects in both
      trafficking and MgADP response of K(ATP) channels. Here we investigated the
      biochemical features of Phe-1388 that control the proper trafficking and function
      of K(ATP) channels by substituting the residue with all other 19 amino acids.
      Whereas surface expression is largely dependent on hydrophobicity, channel
      response to MgADP is governed by multiple factors and involves the detailed
      architecture of the amino acid side chain. Thus, structural features in SUR1
      required for proper channel function are distinct from those required for correct
      protein trafficking. Remarkably, replacing Phe-1388 by leucine profoundly alters
      the physiological and pharmacological properties of the channel. The F1388L-SUR1
      channel has increased sensitivity to MgADP and metabolic inhibition, decreased
      sensitivity to glibenclamide, and responds to both diazoxide and pinacidil.
      Because this conservative amino acid substitution occurs in the SUR2A and SUR2B
      isoforms, the mutation provides a mechanism by which functional diversities in
      K(ATP) channels are generated.

PMID- 12496312
TI  - Aspartate dehydrogenase, a novel enzyme identified from structural and functional
      studies of TM1643.
AB  - The open reading frame TM1643 of Thermotoga maritima belongs to a large family of
      proteins, with homologues in bacteria, archaea, and eukaryotes. TM1643 is found
      in an operon with two other genes that encode enzymes involved in the
      biosynthesis of NAD. In several bacteria, the gene in the position occupied by
      TM1643 encodes an aspartate oxidase (NadB), which synthesizes iminoaspartate as a
      substrate for NadA, the next enzyme in the pathway. The amino acid sequence of
      TM1643 does not share any recognizable homology with aspartate oxidase or with
      other proteins of known functions or structures. To help define the biological
      functions of TM1643, we determined its crystal structure at 2.6A resolution and
      performed a series of screens for enzymatic function. The structure reveals the
      presence of an N-terminal Rossmann fold domain with a bound NAD(+) cofactor and a
      C-terminal alpha+beta domain. The structural information suggests that TM1643 may
      be a dehydrogenase and the active site of the enzyme is located at the interface
      between the two domains. The enzymatic characterization of TM1643 revealed that
      it possesses NAD or NADP-dependent dehydrogenase activity toward l-aspartate but
      no aspartate oxidase activity. The product of the aspartate dehydrogenase
      activity is also iminoaspartate. Therefore, our studies demonstrate that two
      different enzymes, an oxidase and a dehydrogenase, may have evolved to catalyze
      the first step of NAD biosynthesis in prokaryotes. TM1643 establishes a new class
      of amino acid dehydrogenases.

PMID- 12496313
TI  - What's so good about placement learning?

PMID- 12496314
TI  - Role of the clinical tutor.

PMID- 12496317
TI  - Improving the utility of prostate specific antigen (PSA) in the diagnosis of
      prostate cancer: the use of PSA derivatives and novel markers.
AB  - Prostate specific antigen (PSA) testing is now a routine part of the
      investigation of men with suspected prostate cancer. While a very useful test it
      still has its problems, in particular its lack of specificity means abnormal
      results are often caused by benign disease. This review describes the current
      problems with PSA testing in prostate cancer diagnosis and highlights potential
      ways in which these may be reduced.

PMID- 12496316
TI  - Magnesium in stroke treatment.
AB  - Magnesium is involved in multiple physiological processes that may be relevant to
      cerebral ischaemia, including antagonism of glutamate release, NMDA receptor
      blockade, calcium channel antagonism, and maintenance of cerebral blood flow.
      Systemically administered magnesium at doses that double physiological serum
      concentration significantly reduces infarct volume in animal models of stroke,
      with a window of up to six hours after onset and favourable dose-response
      characteristics when compared with previously tested neuroprotective agents.
      Small clinical trials have reported benefit, but results are not statistically
      significant in systematic review. A large ongoing trial (IMAGES) will report in
      2003-4 and further trials are planned.

PMID- 12496318
TI  - The NHS complaints system.
AB  - This paper reviews the methods by which complaints are currently handled within
      the NHS.

PMID- 12496321
TI  - Managing liver failure.
AB  - Liver disease is rare in childhood, but important new developments have altered
      the natural history and outcome. It is important that clinicians are aware of
      these diseases and their management. Acute liver failure is most often due to
      viral hepatitis, paracetamol overdose, or inherited metabolic liver disease. The
      clinical presentation includes jaundice, coagulopathy, and encephalopathy. Early
      diagnosis is necessary to prevent complications such as cerebral oedema,
      gastrointestinal bleeding, and renal failure. Early supportive management, in
      particular intravenous N-acetylcysteine, may be effective but liver
      transplantation is usually the definitive treatment and thus early referral to a
      specialist unit for liver transplantation is mandatory. Chronic liver failure may
      be due to unresolved neonatal liver disease, either inherited biliary hypoplasia
      or extrahepatic biliary atresia, while in older children, autoimmune liver
      disease or cystic fibrosis are the commonest causes. Treatment includes specific
      medication, nutritional support, and liver transplantation, which now has a 90%
      survival with good quality life.

PMID- 12496319
TI  - Epidemiology of perforated colonic diverticular disease.
AB  - Perforated colonic diverticular disease results in considerable mortality and
      morbidity. This review appraises existing evidence on the epidemiology and
      mechanisms of perforation, highlights areas of further study, and suggests an
      epidemiological approach towards preventing the condition. Computerised searches
      were used to identify published articles relating to the epidemiology,
      pathophysiology, and clinical features of perforated colonic diverticular
      disease. Several drug and dietary exposures have potential biological mechanisms
      for causing perforation. Of these only non-steroidal anti-inflammatory drugs have
      been consistently identified as risk factors in aetiological studies. The causes
      of perforated colonic diverticular disease remain largely unknown. Further
      aetiological studies, looking specifically at perforation, are required to
      investigate whether cause-effect relationships exist for both drug and dietary
      exposures. The identification of risk factors for perforation would allow primary
      public health prevention, secondary risk factor modification, and early
      prophylactic surgery to be aimed at people at high risk.

PMID- 12496322
TI  - Costs of waiting for gall bladder surgery.
AB  - Laparoscopic cholecystectomy is one of the most commonly awaited general surgical
      procedures in the UK. However, many patients awaiting a cholecystectomy are
      admitted with recurrent gallstone related symptoms while on the waiting list,
      resulting in significant morbidity. The aim of this study was to quantify this
      problem, and also to analyse the cost implications of these admissions for the
      NHS. A retrospective study was performed of all patients who underwent an
      elective cholecystectomy by three consultants in a district general hospital
      between January 1999 and January 2000. The demographic details, indications for
      surgery, details of the emergency admissions while on the waiting list, and the
      treatment given during these episodes were recorded. One hundred and fifty six
      patients were included in the study, of which 122 (78%) were females. The mean
      (SD) age of the patients was 54 (5) years. The mean waiting time for surgery in
      these patients was 12 (3) months. Thirty seven patients (23.7%) were admitted as
      an emergency due to gallstone related symptoms and complications while awaiting
      surgery. There were 47 episodes of admissions in total, of which 32 were for
      biliary colic, 13 were for acute cholecystitis, and two were for acute
      pancreatitis. In addition to routine blood tests, 20 abdominal radiographs, 10
      chest radiographs, three endoscopic retrograde cholangiopancreatography tests,
      five ultrasonograms, and one computed tomogram were carried out in these
      patients. The mean duration of each episode of admission was three days. The cost
      of treatment per episode was pound 946 and the total cost of treating the 37
      patients was calculated to be pound 44 462. Performing early laparoscopic
      cholecystectomy for acute cholecystitis may help to reduce costs by preventing
      recurrent emergency admissions in these patients. Further studies to identify
      risk factors associated with recurrent symptoms and complications in patients
      with gallstone disease may help to prioritize them for early surgery.

PMID- 12496324
TI  - Defensive practice among psychiatrists: a questionnaire survey.
AB  - OBJECTIVE: There has been little research on the prevalence of defensive practice
      within hospital settings. The aim of this report was to examine the extent of
      defensiveness among psychiatrists and to examine the relationship between
      defensiveness and seniority, as well as the effect of previous experiences on the
      level of defensiveness. DESIGN: A postal questionnaire survey on defensive
      practice. SETTING: Northern Region of England. SUBJECTS: 154 psychiatrists in the
      region. RESULTS: 96 responses were received from 48 equivalent consultants, 18
      specialist registrars, and 23 equivalent senior house officers. Overall, 75% of
      those who replied had taken defensive actions within the past month. In
      particular, 21% had admitted patients overcautiously and 29% had placed patients
      on higher levels of observations. Junior psychiatrists were particularly prone to
      practise defensively. Important contributing factors included previous experience
      of complaints (against colleague or self), critical incidents, and legal claims.
      CONCLUSION: Almost three quarters of the psychiatrists who responded had
      practised defensively within the past month. The higher propensity of junior
      trainees to practise defensively may be attributable to their lack of confidence
      and experience. Experience of complaints (colleague or self) and critical
      incidents were important factors for defensive practice. Better and more
      structured training might reduce the high level of defensive practice and the way
      complaints and investigations are handled should be improved to maintain a truly
      "no blame" environment conducive to learning from past experience.

PMID- 12496325
TI  - Anxiety and depression in an older research population and their impact on
      clinical outcomes in a randomised controlled trial.
AB  - INTRODUCTION: Anxiety and depression are common in older people living in the
      community. The aim of the study was to investigate their impact on clinical
      outcomes during a randomised controlled trial investigating the cost benefits of
      influenza vaccination in fit and healthy, independent living 65-74 year olds.
      SUBJECTS AND METHODS: A total of 729 people were recruited. Participants
      completed the hospital anxiety and depression scale (HADS) and EuroQol EQ-5D
      quality of life questionnaire immediately before receiving vaccination and every
      two months for the next six months after this. Side effects three days after
      vaccination and Barthel score at baseline were also recorded. RESULTS: At
      baseline the prevalence of "definite" anxiety in this sample (HADS score > or
      =11) was 4% and 1.2% of individuals had definite depression (HADS score > or
      =11). Individuals with anxiety or depression (HADS score > or =8) were more
      likely to complain of systemic side effects after vaccination and have a lower
      Barthel index score (p<0.001). Quality of life as measured by the EQ-5D visual
      analogue scale was reduced (p<0.001) at all time periods in those individuals
      with both anxiety and depression (HADS score > or =8 on both scales). CONCLUSION:
      Although the prevalence of anxiety and depression in this sample was low, people
      with anxiety or depression were more likely to suffer from perceived side effects
      after influenza vaccine and have a lower Barthel and EQ-5D visual analogue score.
      In future studies the effect of anxiety and depression on older participants
      should be remembered and care taken to ensure that they do not affect results
      more than the intervention under study.

PMID- 12496326
TI  - Cardiac involvement in HIV infected people in Yaounde, Cameroon.
AB  - OBJECTIVE: To study the cardiac abnormalities in HIV infected patients in
      relation to the clinical stage of the disease and the immunological status of the
      patients. METHODS: A total 75 consecutive patients tested for HIV on the basis of
      clinical suspicion of the disease from July to September 1996 at the University
      Hospital Centre, Yaounde, Cameroon were recruited. The patients were classified
      into AIDS, HIV positive non-AIDS, and HIV negative according to clinical findings
      and outcome of ELISA and western blot testing. Every patient underwent a clinical
      examination, two dimensional and M-mode echocardiography, and blood lymphocyte
      typing. RESULTS: Dilated cardiomyopathy occurred in 7/30 (23.33%) AIDS patients,
      1/24 (4.17%) HIV positive non-AIDS patient, but in none of the HIV negative
      patients. Other echocardiographic abnormalities included pericardial separation,
      effusion, thickening, and mitral valve prolapse. Although these abnormalities
      were more frequent in HIV infected patients, the differences did not reach levels
      of statistical significance. Dilated cardiomyopathy occurred in six (31.58%) of
      the patients with a CD4 cell count < or =100/mm(3) and two (6.06%) in those with
      absolute CD4 counts >100/mm(3) (chi(2) = 4.02, p = 0.03). CONCLUSIONS:
      Cardiovascular abnormalities are frequent in African HIV infected patients but
      clinically discrete. Low CD4 cell counts are associated with dilated
      cardiomyopathy. These abnormalities should be expected with greater frequency in
      cardiological clinical practice as management of opportunistic infections
      improves in a situation of continued high disease prevalence in Africa.

PMID- 12496327
TI  - Thoracoscopic sympathectomy for palmar hyperhidrosis and Raynaud's phenomenon of
      the upper limb and excessive facial blushing: a five year experience.
AB  - Primary hyperhidrosis of the palms, face, and axillae has a strong negative
      impact on social and professional life. A retrospective analysis of 40
      laparoscopic transaxillary thoracic sympathectomies performed in a district
      general hospital over a five year period was undertaken in order to determine the
      effectiveness of this procedure. A postal questionnaire was sent to all patients
      to assess the benefit from the operation; postoperative pain and time off work
      were collated. Immediate failure was noted in three patients, of whom two later
      underwent successful reoperation. Recurrence was noted in three patients (8%).
      Though immediate complications were minimal, the major long term postoperative
      morbidity was compensatory hyperhidrosis on the back, chest, and thigh (77%)
      along with gustatory sweating over the face (22%). Thoracoscopic sympathectomy is
      a safe, effective, and minimally invasive surgical treatment for hyperhidrosis,
      Raynaud's phenomenon of the upper limb, and excessive facial blushing; however,
      the chance of long term compensatory hyperhidrosis is high.

PMID- 12496328
TI  - Polyarteritis nodosa presenting as a pyrexia of unknown origin.
AB  - A case of an 18 year old woman is reported who presented with a pyrexia of
      unknown origin having returned from a trip to India. She initially had
      constitutional symptoms only, which rapidly progressed to a multisystem disorder.
      The difficulty in making the diagnosis of polyarteritis nodosa, especially with
      the possible differential diagnosis of infection after her recent travel, is
      discussed. The discussion reviews the condition of polyarteritis nodosa and
      analyses the diagnostic difficulties in this case.

PMID- 12496329
TI  - Thyrotoxic periodic paralysis in a white woman.
AB  - A 24 year old white woman presented with sudden onset of flaccid quadriparesis
      and hypokalaemia. She was later found to be thyrotoxic. Paralysis resolved with
      potassium supplements, and after initiation of antithyroid medication she had no
      further episodes of hypokalaemic paralysis. To the best of the authors'
      knowledge, and after a Medline search, thyrotoxic periodic paralysis has not been
      described previously in a white woman.

PMID- 12496330
TI  - Bullous lungs: diverse aetiology.

PMID- 12496331
TI  - Young man with progressive weight loss, fevers, and a hilar mass.

PMID- 12496332
TI  - Persistent dizziness.

PMID- 12496333
TI  - Painful knees.

PMID- 12496338
TI  - James Lind's Treatise of the Scurvy (1753).
AB  - Lind is revered as the first doctor to conduct systematic clinical trials of
      potential cures for scurvy-trials in which oranges and lemons came out as
      decisive winners. The following paper argues that our modern understanding of
      scurvy and vitamin C has hindered our understanding of Lind's own conception of
      his work and of the place within it of his clinical trials. Lind conceived of
      scurvy not as a disease of dietary deficiency, but of faulty digestion. In the
      full context of his Treatise of the Scurvy, and of his own medical practice, the
      seeming decisiveness of the trials fades, to be replaced by a sense of Lind's
      bafflement at the nature of the disease to which he had devoted his career.

PMID- 12496339
TI  - Confidence levels of PRHOs in caring for acutely ill patients.

PMID- 12496340
TI  - Knowledge of aspects of acute care in trainee doctors.

PMID- 12496341
TI  - Knowledge of aspects of acute care in trainee doctors.

PMID- 12496342
TI  - Plain abdominal radiographs in acute medical emergencies: an abused
      investigation?

PMID- 12496343
TI  - Plain abdominal radiographs in acute medical emergencies: an abused
      investigation?

PMID- 12496344
TI  - Should inexperienced trainees be delivering acute medical services?

PMID- 12496345
TI  - Vacuum assisted closure system in the management of enterocutaneous fistula.

PMID- 12496346
TI  - Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2
      adrenergic analgesia and analgesic sex differences.
AB  - The analgesia produced by inhibitory G protein-coupled receptor agonists involves
      coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying
      potassium channels (GIRKs) and presynaptic inhibition of neurotransmitter release
      through regulation of voltage-gated Ca(2+) channels. Here, we used mice lacking
      the GIRK2 channel subunit to assess the relative contribution of these two
      effector systems to nociceptive processing in male and female mice. Compared with
      female WT mice, male WT mice exhibited higher pain thresholds and enhanced opioid
      (morphine) and alpha(2)-adrenergic (clonidine) receptor-induced antinociception
      in a spinal reflex test. The GIRK2-null mutation reduced the "pain" threshold in
      male but not in female mice, effectively eliminating the sex differences in pain
      threshold. In addition, deletion of GIRK2 channels in mutant mice largely
      eliminated clonidine antinociception and significantly decreased morphine
      antinociception. Furthermore, the more pronounced morphine and clonidine-induced
      antinociception in male mice disappeared in the GIRK2 mutants. Based on the
      almost complete loss of clonidine-induced antinociception in the mutant mice, we
      conclude that it is primarily mediated by postsynaptic alpha(2)-adrenergic
      receptors. In contrast, the significant residual morphine effect in the mutant
      mice points to the presynaptic mu opioid receptor as a major contributor to its
      analgesic action. Finally, our results suggest that the reduced pain
      responsiveness of male compared with female mice results in part from GIRK2
      coupled postsynaptic receptors that are activated by endogenous antinociceptive
      systems.

PMID- 12496347
TI  - Arachidonic acid mediates muscarinic inhibition and enhancement of N-type Ca2+
      current in sympathetic neurons.
AB  - N-type Ca(2+) channels participate in acute activity-dependent processes such as
      regulation of Ca(2+)-activated K(+) channels and in more prolonged events such as
      gene transcription and long-term depression. A slow postsynaptic M(1) muscarinic
      receptor-mediated modulation of N-type current in superior cervical ganglion
      neurons may be important in regulating these processes. This slow pathway
      inhibits N-type current by using a diffusible second messenger that has remained
      unidentified for more than a decade. Using whole-cell patch-clamp techniques,
      which isolate the slow pathway, we found that the muscarinic agonist oxotremorine
      methiodide not only inhibits currents at positive potentials but enhances N-type
      current at negative potentials. Enhancement was also observed in cell-attached
      patches. These findings provide evidence for N-type Ca(2+)-current enhancement by
      a classical neurotransmitter. Moreover, enhancement and inhibition of current by
      oxotremorine methiodide mimics modulation observed with direct application of a
      low concentration of arachidonic acid (AA). Although no transmitter has been
      reported to use AA as a second messenger to modulate any Ca(2+) current in either
      neuronal or nonneuronal cells, we nevertheless tested whether a fatty acid
      signaling cascade was involved. Blocking phospholipase C, phospholipase A(2), or
      AA but not AA metabolism minimized muscarinic modulation of N-type current,
      supporting the participation of these molecules in the slow pathway. A role for
      the G protein G(q) was also confirmed by blocking muscarinic modulation of Ca(2+)
      currents with anti-G(qalpha) antibody. Our finding that AA participates in the
      slow pathway strongly suggests that it may be the previously unknown diffusible
      second messenger.

PMID- 12496348
TI  - Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of
      schizophrenic and bipolar patients.
AB  - The delineation of dopamine dysfunction in the mentally ill has been a long
      standing quest of biological psychiatry. The present study focuses on a recently
      recognized group of dopamine receptor-interacting proteins as possible novel
      sites of dysfunction in schizophrenic and bipolar patients. We demonstrate that
      the dorsolateral prefrontal cortex in schizophrenia and bipolar cases from the
      Stanley Foundation Neuropathology Consortium display significantly elevated
      levels of the D2 dopamine receptor desensitization regulatory protein, neuronal
      calcium sensor-1. These levels of neuronal calcium sensor-1 were not influenced
      by age, gender, hemisphere, cause of death, postmortem period, alcohol
      consumption, or antipsychotic and mood stabilizing medications. The present study
      supports the hypothesis that schizophrenia and bipolar disorder may be associated
      with abnormalities in dopamine receptor-interacting proteins.

PMID- 12496349
TI  - A smallpox false alarm.

PMID- 12496350
TI  - Smallpox vaccination--the call to arms.

PMID- 12496351
TI  - How contagious is vaccinia?

PMID- 12496352
TI  - The public and the smallpox threat.
AB  - BACKGROUND: The potential for a bioterrorist attack involving smallpox has led to
      a debate about what national precautions should be taken. What is unclear is the
      public's knowledge of smallpox and views about precautions. METHODS: We conducted
      a national survey of 1006 adults selected by means of random-digit dialing.
      Respondents were asked about their knowledge of and beliefs about the smallpox
      virus and the vaccine, their possible reactions to a bioterrorist attack
      involving smallpox, and a number of proposed state emergency powers. RESULTS: The
      majority of the respondents have a number of beliefs about smallpox and smallpox
      vaccination that are false. The majority believe that there is an effective
      treatment for smallpox, that there have been cases of smallpox in the past five
      years, and that there is not enough smallpox vaccine to vaccinate everyone in the
      United States. Thirty percent believe that vaccination earlier in their lives
      would protect them from the disease. The majority of respondents said they wanted
      to be vaccinated; however, only 21 percent would want to be vaccinated if
      physicians declined vaccination. There was strong support among the respondents
      for several proposed state emergency powers. CONCLUSIONS: Our results suggest the
      need for public education about smallpox. These data also point to the importance
      of a discussion in the medical community about the advisability of vaccination of
      individual physicians at this time.

PMID- 12496353
TI  - A model for a smallpox-vaccination policy.
AB  - BACKGROUND: The new reality of biologic terrorism and warfare has ignited a
      debate about whether to reintroduce smallpox vaccination. METHODS: We developed
      scenarios of smallpox attacks and built a stochastic model of outcomes under
      various control policies. We conducted a systematic literature review and
      estimated model parameters on the basis of European and North American outbreaks
      since World War II. We assessed the trade-offs between vaccine-related harms and
      benefits. RESULTS: Nations or terrorists possessing a smallpox weapon could
      feasibly mount attacks that vary with respect to tactical complexity and target
      size, and patterns of spread can be expected to vary according to whether index
      patients are hospitalized early. For acceptable results, vaccination of contacts
      must be accompanied by effective isolation. Vaccination of contacts plus
      isolation is expected to result in 7 deaths (from vaccine or smallpox) in a
      scenario involving the release of variola virus from a laboratory, 19 deaths in a
      human-vector scenario, 300 deaths in a building-attack scenario, 2735 deaths in a
      scenario involving a low-impact airport attack, and 54,729 deaths in a scenario
      involving a high-impact airport attack. Immediate vaccination of the public in an
      attacked region would provide little additional benefit. Prior vaccination of
      health care workers, who would be disproportionately affected, would save lives
      in large local or national attacks but would cause 25 deaths nationally. Prior
      vaccination of health care workers and the public would save lives in a national
      attack but would cause 482 deaths nationally. The expected net benefits of
      vaccination depend on the assessed probability of an attack. Prior vaccination of
      health care workers would be expected to save lives if the probability of a
      building attack exceeded 0.22 or if the probability of a high-impact airport
      attack exceeded 0.002. The probability would have to be much higher to make
      vaccination of the public life-saving. CONCLUSIONS: The analysis favors prior
      vaccination of health care workers unless the likelihood of any attack is very
      low, but it favors vaccination of the public only if the likelihood of a national
      attack or of multiple attacks is high.

PMID- 12496354
TI  - A different view of smallpox and vaccination.

PMID- 12496355
TI  - Imatinib mesylate (STI-571) reduces Bcr-Abl-mediated vascular endothelial growth
      factor secretion in chronic myelogenous leukemia.
AB  - A large and diverse spectrum of oncogenes has been implicated as a contributor to
      angiogenesis in solid tumors based, in part, on its ability to induce
      proangiogenic growth factors such as vascular endothelial growth factor (VEGF),
      and the fact that various anti-oncogenic signaling inhibitor drugs have been
      shown to reverse such proangiogenic effects both in vitro and in vivo. Because
      leukemias are now also considered to be angiogenesis-dependent malignancies, we
      asked whether a similar paradigm might exist for the BCR-ABL oncogene and the Bcr
      Abl targeting drug, STI-571 (imatinib mesylate), in the context of chronic
      myelogenous leukemia (CML) cells. We found that levels of VEGF expression in BCR
      ABL-positive K562 cells were reduced in vitro by treatment with STI-571 in a dose
      dependent fashion. Transfection of BCR-ABL into murine myeloid 32D and human
      megakaryocyte MO7e hematopoietic cells resulted in enhanced VEGF expression,
      which could be further elevated by the exposure to cytokines such as interleukin
      3 and granulocyte macrophage colony-stimulating factor. We also found that
      conditioned media taken from 32D-p210-transfected cells could stimulate human
      umbilical vein endothelial cells by increasing phosphorylation of VEGF-R2/KDR and
      the downstream serine/threonine kinase PKB/Akt, an important regulator of
      endothelial cell survival. Moreover, amplification of BCR-ABL in STI-571
      resistant cells was associated with elevated VEGF expression levels which could
      be reversed by treatment with higher concentrations of STI-571. Taken together,
      our results implicate BCR-ABL as a possible regulator of CML angiogenesis and
      raise the possibility that STI-571 could mediate some of its anti-CML properties
      in vivo through an angiogenesis-dependent mechanism.

PMID- 12496356
TI  - A fucosylated chondroitin sulfate from echinoderm modulates in vitro fibroblast
      growth factor 2-dependent angiogenesis.
AB  - Fucosylated chondroitin sulfate (FucCS), a glycosaminoglycan obtained from sea
      cucumber, has the same structure as mammalian chondroitin sulfate, but some of
      the glucuronic acid residues display sulfated fucose branches. This new
      polysaccharide has a more favorable effect than heparin on vascular cell growth.
      It inhibits smooth muscle cell proliferation as heparin, and it has a potent
      enhancing effect on endothelial cell proliferation and migration in the presence
      of heparin-binding growth factors. We now extend our studies to the effect of
      this glycosaminoglycan on endothelial cells to an in vitro angiogenesis model on
      Matrigel. FucCS, in the presence of fibroblast growth factor-2 (FGF-2), strongly
      increases the capacity of endothelial cells to form vascular tubes on Matrigel
      with a well-organized capillary-like network and typical closed structures.
      Comparison between the activity of native and chemically modified chondroitin
      sulfate from sea cucumber reveals that the sulfated fucose branches are the
      structural motif for the proangiogenic activity. Heparin does not induce
      angiogenesis in this experimental model. We also have evidence for the
      proposition that endothelial cell proliferation is not the sole event involved in
      the in vitro FGF-2-induced angiogenesis. It implies a variety of other
      modifications of the endothelial cells and of their interaction with the
      extracellular matrix, such as integrin expression and actin cytoskeleton
      reorganization. Finally, the proangiogenic effect of FucCS, concomitant with its
      capacity to prevent venous and arterial thrombosis, in animal models makes this
      new glycosaminoglycan a promising molecule with possible beneficial effects in
      pathological conditions affecting blood vessels such as the neovascularization of
      ischemic areas.

PMID- 12496357
TI  - Damage recovery pathways in Saccharomyces cerevisiae revealed by genomic
      phenotyping and interactome mapping.
AB  - We have generated a genomic phenotyping database identifying hundreds of
      Saccharomyces cerevisiae genes important for viable cellular recovery after
      mutagen exposure. Systematic phenotyping of 1,615 gene deletion strains produced
      distinctive signatures for each of four mutagens. Integration of the phenotyping
      database with mutagen-induced transcriptional profiling data demonstrated that
      being transcriptionally responsive to a mutagen does not predict whether or not a
      gene contributes to recovery from exposure to that mutagen. Computational
      integration of the database with 4,025 interacting proteins, comprising the yeast
      interactome, identified several multiprotein networks important for damage
      recovery. Some networks were associated with DNA metabolism and cell cycle
      control functions, but most were associated with unexpected functions such as
      cytoskeleton remodeling, chromatin remodeling, protein, RNA, and lipid
      metabolism. Hence, a plethora of responses other than the DNA damage response is
      important for recovery. These network mapping results demonstrate how systematic
      phenotypic assays may be linked directly to underlying molecular mechanisms.

PMID- 12496358
TI  - Prostate stem cell antigen is a marker of late intermediate prostate epithelial
      cells.
AB  - Prostate stem cell antigen (PSCA, named for its strong sequence homology to the
      thymocyte marker stem cell antigen 2) is a cell surface antigen expressed in
      normal prostate and associated with human and murine prostate cancer. To begin to
      investigate a possible link between PSCA expression in normal prostate and
      prostate carcinogenesis, we characterized the phenotype and proliferative
      behavior of normal PSCA-expressing prostate epithelial cells (PrEC) in tissue
      culture. PSCA was expressed in a subset of prostate epithelial cells that
      coexpress basal and secretory cytokeratins. PSCA-positive cells were the direct
      progeny of PSCA-negative cells and were characterized by a more differentiated
      morphology and a slower proliferative rate than PSCA-negative cells. Although
      PSCA-positive cells continued to express basal cell markers such as CD44, they
      lost expression of the basal cell marker p63. In contrast, expression of prostate
      specific antigen and androgen receptor transcripts was detectable in PSCA
      positive PrEC. These findings suggest that PSCA is a unique marker of an
      intermediate subpopulation of PrEC in transition from a basal to a terminally
      differentiated secretory phenotype and may be a useful marker for the study of
      normal and malignant prostate development.

PMID- 12496359
TI  - Apoptosis of mortal human fibroblasts transformed by the bovine papillomavirus E5
      oncoprotein.
AB  - Mortal human fibroblasts can be partially transformed by the bovine
      papillomavirus E5 oncoprotein through activation of the platelet-derived growth
      factor beta receptor. Here, we report that these cells undergo massive apoptosis
      2 weeks after confluence. Although activation of caspase 3 was observed in the
      apoptotic cells, it was not required for apoptosis. The appearance of the
      mitochondrial proteins cytochrome c and apoptosis-inducing factor in cytosolic
      and nuclear compartments, respectively, provided a basis for mitochondrial
      dysfunction and a caspase-independent mechanism of apoptosis in these cells.
      Although an activating conformational change in Bax also was evident in the
      apoptotic cells, enforced overexpression of Bcl-2 was insufficient to prevent
      apoptosis. Finally, a small peptide present in the conditioned medium from dying
      transformed cells appeared responsible for inducing apoptosis through affecting a
      conformational change in Bax and eventual relocalization of apoptosis-inducing
      factor to the nucleus. Thus, an atypical apoptotic pathway is activated in mortal
      human fibroblasts in response to transformation induced by sustained receptor
      tyrosine kinase activation.

PMID- 12496360
TI  - Role of reactive oxygen species in cells overexpressing manganese superoxide
      dismutase: mechanism for induction of radioresistance.
AB  - Manganese superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide
      anions (O(2)(-)) into hydrogen peroxide (H(2)O(2)). We altered the intracellular
      status of reactive oxygen species by introducing human MnSOD cDNA into the human
      ovarian cancer cell line SK-OV-3. The overexpression of MnSOD inhibited cell
      growth and induced a concomitant increase in the level of H(2)O(2) in SK-OV-3
      cells. The cells overexpressing MnSOD were more resistant to irradiation than
      parental cells. MnSOD overexpression shortened the G(2)-M duration in irradiated
      cells. Either inhibition of p38 mitogen-activated protein kinase (p38MAPK) or
      scavenging free radicals blocked the induction of radioresistance by MnSOD and
      also abolished the shortening of the G(2)-M duration with concomitant inhibition
      of p38MAPK phosphorylation. Irradiation increased the generation of H(2)O(2) even
      more in these transfectants. These results suggest that the accumulated H(2)O(2)
      potentiated the activation of p38MAPK after irradiation in cells overexpressing
      MnSOD, which led to the protection of cells from irradiation-mediated cell death
      through the G(2)-M checkpoint. SK-OV-3 cells had no constitutive expression of
      p53, and the overexpression of MnSOD and/or irradiation did not induce p53 or
      p21(WAF1), which causes cell cycle arrest. Thus, our results suggest that MnSOD
      alters the cell cycle progression of irradiated cells independently of p53 and
      p21(WAF1).

PMID- 12496361
TI  - Extracellular signal-regulated protein kinase signaling is uncoupled from initial
      differentiation of central nervous system stem cells to neurons.
AB  - Knowledge about signaling pathways in response to external signals is needed to
      understand the regulation of stem cell proliferation and differentiation toward
      particular cell fates. The Ras/extracellular signal-regulated kinase (ERK)
      pathway has been suggested to play an essential role in neuronal differentiation.
      We have examined ERK signaling in the transition from multipotent stem cell to
      post-mitotic progeny using primary stem cells from the rat embryonic cortex.
      Fibroblast growth factor-2 (FGF-2) is a stem cell mitogen, whereas platelet
      derived growth factor AA (PDGF-AA) expands a pool of committed neuronal
      precursors from stem cells. When comparing ERK activation by these growth
      factors, we found that FGF-2 stimulates high and PDGF-AA lower levels of ERK
      phosphorylation in stem cells. Differentiation was monitored as down-regulation
      of the bHLH transcription factor mammalian achaete-scute homologue-1 (MASH1).
      Even in the absence of active ERK, MASH1 became down-regulated and microtubule
      associated protein 2-positive cells could form. Thus, ERK activation seems
      dispensable for the earliest steps of CNS stem cell differentiation.

PMID- 12496362
TI  - Regulation of Lck and Fyn tyrosine kinase activities by transmembrane protein
      tyrosine phosphatase leukocyte common antigen-related molecule.
AB  - Leukocyte common antigen-related molecule (LAR) is a receptor-like protein
      tyrosine phosphatase (PTPase) with two PTPase domains. In the present study, we
      detected the expression of LAR in the brain, kidney, and thymus of mice using
      anti-LAR PTPase domain subunit monoclonal antibody (mAb) YU1. In the thymus, LAR
      was expressed on CD4(-)CD8(-) and CD4(-)CD8(low) thymocytes. The development of
      thymocytes in CD45 knockout mice is blocked partially in the maturation of CD4(
      )CD8(-) to CD4(+)CD8(+). We postulated that LAR regulates Lck and Fyn in the
      immature thymocytes. Transfection of wild-type LAR activated extracellular signal
      regulated kinase signal transduction pathway in CD45-deficient Jurkat cells
      stimulated with anti-CD3 mAb. LAR mutants, with Cys to Ser mutation in the
      catalytic center of PTPase D1, bound to tyrosine-phosphorylated Lck and Fyn, and
      LAR PTPase domain 2 was tyrosine phosphorylated by Fyn tyrosine kinase. The
      phosphorylated LAR was associated with Fyn Src homology 2 domain. Moreover, LAR
      dephosphorylated phosphorylated tyrosine residues in both the COOH terminus and
      kinase domain of Fyn in vitro. Our results indicate that Lck and Fyn would be
      substrates of LAR in immature thymocytes and that each LAR PTPase domain plays
      distinct functional roles in phosphorylation and dephosphorylation.

PMID- 12496364
TI  - Blockade of EphA receptor tyrosine kinase activation inhibits vascular
      endothelial cell growth factor-induced angiogenesis.
AB  - Angiogenesis is a multistep process involving a diverse array of molecular
      signals. Ligands for receptor tyrosine kinases (RTKs) have emerged as critical
      mediators of angiogenesis. Three families of ligands, vascular endothelial cell
      growth factors (VEGFs), angiopoietins, and ephrins, act via RTKs expressed in
      endothelial cells. Recent evidence indicates that VEGF cooperates with
      angiopoietins to regulate vascular remodeling and angiogenesis in both
      embryogenesis and tumor neovascularization. However, the relationship between
      VEGF and ephrins remains unclear. Here we show that interaction between EphA RTKs
      and ephrinA ligands is necessary for induction of maximal neovascularization by
      VEGF. EphA2 RTK is activated by VEGF through induction of ephrinA1 ligand. A
      soluble EphA2-Fc receptor inhibits VEGF-, but not basic fibroblast growth factor
      induced endothelial cell survival, migration, sprouting, and corneal
      angiogenesis. As an independent, but complementary approach, EphA2 antisense
      oligonucleotides inhibited endothelial expression of EphA2 receptor and
      suppressed ephrinA1- and VEGF-induced cell migration. Taken together, these data
      indicate an essential role for EphA receptor activation in VEGF-dependent
      angiogenesis and suggest a potential new target for therapeutic intervention in
      pathogenic angiogenesis.

PMID- 12496365
TI  - CDK5 regulates cell adhesion and migration in corneal epithelial cells.
AB  - CDK5 and its activator, p35, are expressed in mouse corneal epithelium and can be
      coimmunoprecipited from corneal epithelial cell lysates. Immunostaining shows
      CDK5 and p35 in all layers of the corneal epithelium, especially along the basal
      side of the basal cells. Stable transfection of corneal epithelial cells with
      CDK5, which increases CDK5 kinase activity by approximately 33%, also increases
      the number of cells adhering to fibronectin and the strength of adhesion. CDK5
      kinase activity seems to be required for this effect, because the kinase inactive
      mutation, CDK5-T33, either reduces adhesion or has no significant effect,
      depending on the level of expression. Using an in vitro scrape wound in confluent
      cultures of stably transfected cells to examine the effect of CDK5 on cell
      migration, we show that reoccupation of the wound area is significantly decreased
      by CDK5 and increased by CDK5-T33. These findings indicate that CDK5 may be an
      important regulator of adhesion and migration of corneal epithelial cells.

PMID- 12496366
TI  - Defective 3A trophoblast-endometrial cell adhesion and altered 3A growth and
      survival by human papillomavirus type 16 oncogenes.
AB  - Human papillomaviruses (HPVs) are found in trophoblasts of spontaneous abortions
      and replicate in these cells in culture. We used recombinant adeno-associated
      viruses (rAAV) to introduce the HPV-16 E6 and E7 oncogenes into 3A trophoblasts.
      AAV/E7/Neo-infected 3A trophoblasts died rapidly, but AAV/E6/Neo- and AAV/E6
      E7/Neo-infected cells grew more rapidly than AAV/Neo-infected 3A cells and
      parental 3A. After G418 selection, the resulting E6-E7/3A and E6/3A cell lines
      were found to be highly defective for binding RL95 and HEC endometrial cells
      compared to Neo/3A and parental 3A. Serum requirements and soft agar colony
      formation analysis showed that E6-E7/3A had the most malignant phenotype,
      followed by E6/3A, with parental 3A cells having the lowest. E6/3A and E6-E7/3A
      were also immortal. Thus, HPV-16 oncogene expression may lead to outright
      trophoblast death, defective endometrial cell recognition, or a malignant
      phenotype. Any of these changes might lead to disruption/dysfunction of the
      trophoblast layer/gestational loss.

PMID- 12496367
TI  - Overexpression and forced activation of stat5 in mammary gland of transgenic mice
      promotes cellular proliferation, enhances differentiation, and delays
      postlactational apoptosis.
AB  - Signal transducer and activator of transcription 5 (Stat5) transduces
      extracellular cytokine and growth factor signals to the nucleus of mammary
      epithelial cells and thereby regulates gene transcription during pregnancy,
      lactation, and weaning. Gene constructs were prepared which subject the wild-type
      Stat5 or a constitutively active variant of Stat5 to the control of the beta
      lactoglobulin (BLG) regulatory sequences and direct it to the mammary epithelium.
      The integrity and functionality of these constructs were confirmed through
      introduction into cultured mammary epithelial cells and hormone induction
      experiments. Expression levels and states of activity of Stat5 in mammary gland
      tissue were manipulated by introducing Stat5 variants as transgenes into the
      pronuclei of transgenic mice. The consequences of enhanced Stat5 expression and
      activation on the development of alveoli, their differentiated functions, and on
      postlactational involution were investigated. As expected, the transgenic mouse
      lines expressed the wild-type Stat5 construct (BLG/STAT5) and the constitutively
      active Stat5 variant (BLG/STAT5ca) exclusively in mammary epithelial cells during
      pregnancy and lactation. BLG/STAT5 mice exhibited larger alveoli at mid-pregnancy
      and a delayed onset of involution. Condensed alveoli, a high degree of cellular
      proliferation, and delayed involution were associated with STAT5ca expression.
      Elevated levels of beta-casein gene expression were found in BLG/STAT5 and
      STAT5ca transgenic mice during late pregnancy and lactation, indicating a
      limiting role for Stat5 under normal physiological conditions. This was
      accompanied by higher levels of beta-casein secretion into the milk and enhanced
      growth of pups. Transgenic animals expressing the BLG/STAT5ca transgene were
      predisposed to tumor formation in the mammary gland. This study extends the
      functional observations made in cultured mammary epithelial cells and in gene
      knockout mice. It identifies Stat5 as a multifunctional regulator of mammary cell
      proliferation, milk protein gene expression, and postlactational apoptosis.

PMID- 12496368
TI  - Physical and functional interaction between the transcriptional cofactor CBP and
      the KH domain protein Sam68.
AB  - CBP is a multifunctional transcriptional cofactor with tumor suppressor activity.
      The CH3 domain of CBP binds numerous transcription factors and several viral
      oncoproteins. We identified the Src substrate and RNA-binding protein Sam68 as
      novel CH3-binding protein. Sam68 binds the CH3 domain in part through a conserved
      FXD/EXXXL motif that is shared among several CH3-binding proteins, including the
      adenoviral oncoprotein E1A and the tumor suppressor p53. Sam68 and CBP interact
      in vivo and colocalize in nuclear sub-domains. Sam68 has potent transcriptional
      repression activity that is independent of its RNA binding activity, which
      suggests that RNA processing and regulation of gene expression by Sam68 are
      separable functions. Consistent with this, CBP did not stimulate the ability of
      Sam68 to promote Rev response element-containing mRNA export. Interestingly,
      Sam68 can regulate RNA processing in the absence of a Rev response element,
      suggesting that Sam68 functions through a novel RNA element. Together, these
      findings reveal a previously unidentified function for Sam68 as a transcriptional
      repressor and suggest that Sam68 might link cellular signaling pathways with
      components of the transcriptional machinery.

PMID- 12496369
TI  - Targeted disruption of the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in ras
      transformed keratinocytes demonstrates that locally produced 1alpha,25
      dihydroxyvitamin D3 suppresses growth and induces differentiation in an autocrine
      fashion.
AB  - It has been previously shown that keratinocytes express a high level of 25
      hydroxyvitamin D(3) (25-OHD(3)) 1alpha-hydroxylase (1alpha-hydroxylase). 1alpha
      Hydroxylase catalyzes the conversion of 25-OHD(3) to 1alpha,25-dihydroxyvitamin
      D(3) [1,25(OH)(2)D(3)]. 1,25(OH)(2)D(3) is both antiproliferative (i.e.,
      suppresses cell growth) and prodifferentiative (i.e., induces cell
      differentiation) in many cell types. We hypothesized that local production of
      1,25(OH)(2)D(3) by keratinocytes may suppress their growth and induce their
      differentiation in an autocrine fashion. To test this hypothesis, we inactivated
      both 1alpha-hydroxylase alleles in a ras-transformed keratinocyte cell line,
      HPK1Aras, which typically produces squamous carcinoma in nude mice. To inactivate
      1alpha-hydroxylase expression by HPK1Aras cells, we disrupted both alleles of the
      1alpha-hydroxylase gene by homologous recombination. Lack of expression and
      activity of 1alpha-hydroxylase was confirmed by Northern blot analysis and
      detected conversion of 25-OHD(3) to 1,25(OH)(2)D(3). We then examined the effect
      of substrate 25-OHD(3) on parameters of growth and differentiation in the double
      knockout cell line as compared to wild-type HPK1Aras cells in vitro. It was found
      that 1alpha-hydroxylase inactivation blocked the antiproliferative and
      prodifferentiative effect of 25-OHD(3). These in vitro effects were further
      analyzed in vivo by injecting knockout or control cells subcutaneously in
      severely compromised immunodeficient mice. Tumor growth was accelerated and
      differentiation was inhibited in mice given injections of knockout cells as
      compared to control cells in the presence of substrate 25-OHD(3). Our results
      demonstrate, for the first time, that 1alpha-hydroxylase expression by
      keratinocytes plays an important role in autocrine growth and differentiation of
      these cells, and suggest that expression of this enzyme may modulate tumor growth
      in squamous carcinomas.

PMID- 12496370
TI  - The epithelial mesenchymal transition confers resistance to the apoptotic effects
      of transforming growth factor Beta in fetal rat hepatocytes.
AB  - Fetal rat hepatocytes treated with transforming growth factor beta (TGF-beta) die
      by apoptosis. However, a subpopulation of them survives and undergoes an
      epithelial mesenchymal transition (EMT). This transition also occurs upon
      incubation with fetal bovine serum. We have isolated the subpopulations that
      undergo EMT (TGF-beta-treated-fetal hepatocytes: TbetaT-FH; serum-treated-fetal
      hepatocytes: ST-FH) and show that they present high levels of vimentin and Snail
      expression and lack cytokeratin 18 and E-cadherin. Both TbetaT-FH and ST-FH cells
      require mitogens to grow and maintain the response to TGF-beta in terms of growth
      inhibition. However, they lack differentiation markers such as the liver-enriched
      transcription factors hepatocyte nuclear factor 4 (HNF-4) or HNF-1alpha and
      express the progenitor marker OV-6. Interestingly, the EMT process confers them
      resistance to the apoptotic effect of TGF-beta, with cells showing higher levels
      of active AKT and Bcl-x(L) than fetal hepatocytes. In summary, these cells are
      refractory to the apoptotic effects of TGF-beta, showing characteristics of liver
      progenitors and of some hepatocellular carcinoma cells.

PMID- 12496371
TI  - c-Cbl-dependent EphA2 protein degradation is induced by ligand binding.
AB  - The EphA2 receptor protein tyrosine kinase is overexpressed and functionally
      altered in a large number of human carcinomas. Despite its elevated levels in
      cancer, the EphA2 on the surface of malignant cells demonstrates lower levels of
      ligand binding and tyrosine phosphorylation than the EphA2 on non-transformed
      epithelial cells. In our present study, we demonstrate that ligand-mediated
      stimulation causes EphA2 to be internalized and degraded. The mechanism of this
      response involves ligand-mediated autophosphorylation of EphA2, which promotes an
      association between EphA2 and the c-Cbl adaptor protein. We also show that c-Cbl
      promotes stimulation-dependent EphA2 degradation. These findings are important
      for understanding the causes of EphA2 overexpression in malignant cells and
      provide a foundation for investigating EphA2 as a potential target for
      therapeutic intervention.

PMID- 12496374
TI  - Cutting edge: targeting of V beta to D beta rearrangement by RSSs can be mediated
      by the V(D)J recombinase in the absence of additional lymphoid-specific factors.
AB  - Assembly of TCRbeta variable region genes is ordered during thymocyte development
      with Dbeta to Jbeta rearrangement preceding Vbeta to DJbeta rearrangement. The
      5'Dbeta 12-RSS is required to precisely and efficiently target Vbeta
      rearrangement beyond simply enforcing the 12/23 rule. By prohibiting direct Vbeta
      to Jbeta rearrangement, this restriction ensures Dbeta gene segment use in the
      assembly of essentially all TCRbeta variable region genes. In this study, we show
      that rearrangement of Vbeta 23-RSSs is significantly biased to the Dbeta 12-RSS
      over Jbeta 12-RSSs on extrachromosomal recombination substrates in nonlymphoid
      cells that express the recombinase-activating gene-1/2 proteins. These findings
      demonstrate that targeting of Vbeta to Dbeta rearrangement can be enforced by the
      V(D)J recombinase in the absence of lymphoid-specific factors other than the
      recombinase-activating gene-1/2 proteins.

PMID- 12496375
TI  - Cutting edge: identification of the targets of clonal deletion in an
      unmanipulated thymus.
AB  - Autoreactive thymocytes can be eliminated by clonal deletion during their
      development in the thymus. The precise developmental stage(s) at which clonal
      deletion occurs in a normal thymus has been difficult to assess, in large part
      because of the absence of a specific marker for TCR-mediated apoptosis. In this
      report, we reveal that Nur77 expression can be used as a specific marker of
      clonal deletion in an unmanipulated thymus and directly identify TCRintCD4+CD8+
      and semimature CD4+CD8- thymocytes as the principal targets of deletion. These
      data indicate that clonal deletion normally occurs at a relatively late stage of
      development, as cells mature from CD4+CD8+ thymocytes to single-positive T cells.

PMID- 12496376
TI  - Cutting edge: bacterial lipoprotein induces endotoxin-independent tolerance to
      septic shock.
AB  - Tolerance to bacterial cell wall components is an adaptive host response.
      Endotoxin/LPS tolerance is characterized by a survival advantage against
      subsequent lethal LPS challenge. However, it is uncertain whether LPS tolerance
      can afford protection against other septic challenges. In this study, we show
      that tolerance induced by bacterial lipoprotein (BLP) protects mice against not
      only BLP-induced lethality, but also LPS-, live bacteria-, and polymicrobial
      sepsis-induced lethality. In contrast, LPS tolerance offers no survival benefit
      against the latter two challenges. Furthermore, induction of BLP tolerance
      results in overexpression of complement receptor type 3 and FcgammaIII/IIR on
      neutrophils (polymorphonuclear neutrophils) and peritoneal macrophages, with
      increased bacterial recognition and bactericidal activity, whereas LPS-tolerized
      mice exhibit an impaired ability to ingest and to kill bacteria. These results
      indicate that BLP tolerance is a novel adaptive host response associated with a
      unique protective effect during septic shock.

PMID- 12496377
TI  - Cutting edge: induced expression of a RhoA-specific guanine nucleotide exchange
      factor, p190RhoGEF, following CD40 stimulation and WEHI 231 B cell activation.
AB  - Stimulation of the B cell surface receptor CD40 induces transcriptional
      activation and protein expression. To determine which proteins are required for
      the CD40-mediated B cell activation, we performed a two-dimensional gel
      electrophoresis of the WEHI 231 B cell lysates. We report in this study the
      identification of one protein in which the expression was remarkably induced
      following CD40 stimulation. It was the p190 Rho guanine nucleotide exchange
      factor (GEF), p190RhoGEF, a recently identified GEF that is specific for RhoA.
      Overexpression of either p190RhoGEF or RhoA (Q63L), a constitutively active form
      of RhoA, mimics the effects of CD40 stimulation, such as changes in cellular
      structure and NF-kappaB activation. These p190RhoGEF overexpression effects are
      abrogated when coexpressed with a dominant negative form of RhoA (T19N). We also
      provide evidence for the CD40-mediated cellular changes that are abrogated in
      cells that are overexpressed with the dominant negative form of either p190RhoGEF
      (Y1003A) or RhoA (T19N).

PMID- 12496378
TI  - Cutting edge: dissociation between autoimmune response and clinical disease after
      vaccination with dendritic cells.
AB  - Autoimmunity represents a caveat to the use of dendritic cells (DCs) as adjuvant
      for human vaccines. We derived DCs from normal BALB/c mice or from mice prone to
      autoimmunity (NZB x NZW) F(1). We allowed DCs to phagocytose apoptotic thymocytes
      and vaccinated syngeneic animals. All mice developed anti-nuclear and anti-dsDNA
      Abs. Autoantibodies in normal mice were transient, without clinical or
      histological features of autoimmunity or tissue involvement. In contrast,
      autoimmunity was maintained in susceptible mice, which underwent renal failure
      and precociously died. The data suggest that DC vaccination consistently triggers
      autoimmune responses. However, clinical autoimmunity develops in susceptible
      subjects only.

PMID- 12496379
TI  - Cutting edge: L-selectin (CD62L) expression distinguishes small resting memory
      CD4+ T cells that preferentially respond to recall antigen.
AB  - Naive CD4+ T cells use L-selectin (CD62L) expression to facilitate immune
      surveillance. However, the reasons for its expression on a subset of memory CD4+
      T cells are unknown. We show that memory CD4+ T cells expressing CD62L were
      smaller, proliferated well in response to tetanus toxoid, had longer telomeres,
      and expressed genes and proteins consistent with immune surveillance function.
      Conversely, memory CD4+ T cells lacking CD62L expression were larger,
      proliferated poorly in response to tetanus toxoid, had shorter telomeres, and
      expressed genes and proteins consistent with effector function. These findings
      suggest that CD62L expression facilitates immune surveillance by programming CD4+
      T cell blood and lymph node recirculation, irrespective of naive or memory CD4+ T
      cell phenotype.

PMID- 12496380
TI  - Expression of the murine CD27 ligand CD70 in vitro and in vivo.
AB  - The interaction between TNFR family member CD27 and its ligand CD70 promotes
      lymphocyte expansion and effector cell formation. In humans, control of CD27
      function is partly regulated by the restricted expression of CD70. We used newly
      developed mAbs to characterize murine (m) CD70 expression in vitro and in vivo.
      On resting lymphocytes and immature dendritic cells (DC), mCD70 is absent. In
      vitro, Ag receptor triggering induced mCD70 mRNA in T cells, but cell surface
      protein expression was very low. Activated B cells synthesized much higher levels
      of mCD70 mRNA than activated T cells and clearly expressed mCD70 at the cell
      surface. mCD70 cell surface expression could also be induced on the DC line D1
      and on in vitro-generated murine DC upon maturation. In lymphoid organs of naive
      mice, virtually no mCD70-expressing cells were found, with exception of cells in
      the thymic medulla, which may be epithelial in origin. However, after intranasal
      infection with influenza virus, lung-infiltrating T cells and T and B cells in
      draining lymph nodes expressed mCD70 according to immunohistology. In such
      activated lymphocytes, mCD70 protein is largely retained intracellularly. Plasma
      membrane expression of mCD70 was only detectable by flow cytometry on a small
      proportion of lung-infiltrating T cells and peaked at the height of the primary
      response. Thus, expression of CD70 in the mouse is highly regulated at the
      transcriptional and posttranslational level. This most likely serves to limit
      excessive effector cell formation after antigenic stimulation.

PMID- 12496381
TI  - Guanine exchange-dependent and -independent effects of Vav1 on integrin-induced T
      cell spreading.
AB  - Vav1 is a 95-kDa member of the Dbl family of guanine exchange factors and a
      prominent hemopoietic cell-specific protein tyrosine kinase substrate, the
      involvement of which in cytoskeletal rearrangements has been linked to its
      ability to activate Rho family small GTPases. Beta1 integrin ligation by
      fibronectin induced Vav1 phosphorylation in peripheral blood lymphocytes and in
      two different T cell lines. Vav1 overexpression led to massive T cell spreading
      on beta1 integrin ligands, and, conversely, two dominant negative mutants blocked
      integrin-induced spreading. Vav1 and beta1 integrin ligation synergistically
      activated Pak, but not Rac, Cdc42, or c-Jun N-terminal kinase. In addition, Vav1
      cooperated with constitutively active V12Rac mutant, but not with V12Cdc42, to
      induce T cell spreading after integrin occupancy. More importantly, a Vav1 mutant
      that lacked guanine exchange factor activity still cooperated with V12Rac. In
      contrast, a point mutation in the SH2 domain of Vav1 abolished this synergistic
      effect. Therefore, our results suggest a new regulatory effect of Vav1 in T cell
      spreading, which is independent of its guanine exchange factor activity.

PMID- 12496382
TI  - Recognition of a specific self-peptide: self-MHC class II complex is critical for
      positive selection of thymocytes expressing the D10 TCR.
AB  - We examined the specificity of positive and negative selection by using
      transgenic mice carrying a variant of the D10 TCR. We demonstrate that a point
      mutation at position 51 within the CDR2alpha segment significantly reduces the
      avidity of this TCR for its cognate ligand, but does not impact recognition of
      nonself MHC class II molecules. Although structural studies have suggested that
      this TCR site interacts with the MHC class II beta-chain, the avidity of this TCR
      for its ligand and the function of the T cell can be reconstituted by a point
      mutation in the bound antigenic peptide. These data demonstrate that the bound
      peptide can indirectly alter TCR interactions by influencing MHC structure.
      Remarkably, reducing the avidity of this TCR for a specific antigenic peptide-MHC
      ligand has a dramatic impact on thymic selection. Positive selection of
      thymocytes expressing this TCR is nearly completely blocked, whereas negative
      selection on allogenic MHC class II molecules remains intact. Therefore, the
      recognition of self that promotes positive selection of the D10 TCR is highly
      peptide-specific.

PMID- 12496383
TI  - Strong differential regulation of serum and mucosal IgA responses as revealed in
      CD28-deficient mice using cholera toxin adjuvant.
AB  - In this study, we show that costimulation required for mucosal IgA responses is
      strikingly different from that needed for systemic responses, including serum
      IgA. Following oral immunization with cholera toxin (CT) adjuvant we found that
      whereas CTLA4-H1 transgenic mice largely failed to respond, CD28-/- mice
      developed near normal gut mucosal IgA responses but poor serum Ab responses. The
      local IgA response was functional in that strong antitoxic protection developed
      in CT-immunized CD28-/- mice. This was in spite of the fact that no germinal
      centers (GC) were observed in the Peyer's patches, spleen, or other peripheral
      lymph nodes. Moreover, significant somatic hypermutation was found in isolated
      IgA plasma cells from gut lamina propria of CD28-/- mice. Thus, differentiation
      to functional gut mucosal IgA responses against T cell-dependent Ags does not
      require signaling through CD28 and can be independent of GC formations and
      isotype-switching in Peyer's patches. By contrast, serum IgA responses, similar
      to IgG-responses, are dependent on GC and CD28. However, both local and systemic
      responses are impaired in CTLA4-Hgamma1 transgenic mice, indicating that mucosal
      IgA responses are dependent on the B7-family ligands, but require signaling via
      CTLA4 or more likely a third related receptor. Therefore, T-B cell interactions
      leading to mucosal as opposed to serum IgA responses are uniquely regulated and
      appear to represent separate events. Although CT is known to strongly up-regulate
      B7-molecules, we have demonstrated that it acts as a potent mucosal adjuvant in
      the absence of CD28, suggesting that alternative costimulatory pathways are
      involved.

PMID- 12496384
TI  - Intracellular calcium waves accompany neutrophil polarization,
      formylmethionylleucylphenylalanine stimulation, and phagocytosis: a high speed
      microscopy study.
AB  - Using high sensitivity fluorescence imaging with shutter speeds approximately
      600,000 times faster than those of video frames, we have characterized Ca2+ waves
      within cells in exquisite detail to reveal Ca2+ signaling routes. Polarized
      neutrophils exhibited a counterclockwise rotating ryanodine-sensitive
      juxtamembrane Ca2+ wave during temporal calcium spikes. During stimulation with
      fMLP, a chemotactic factor, two Ca2+ waves traveling in opposite directions
      around the perimeter of the cell emanated from sites of stimulation (the
      clockwise wave is verapamil sensitive). Phagocytosed targets exhibit
      counterclockwise Ca2+ waves traveling about their periphery originating from the
      plasma membrane. This study: 1) outlines the technology to observe Ca2+ signaling
      circuitry within small living cells; 2) shows that extracellular spatial
      information in the form of a chemotactic factor gradient is transduced into
      intracellular chemical patterns, which provides fresh insights in signaling; 3)
      suggests that a line of communication exits between the cell surface and
      phagosomes; and 4) suggests that spatiotemporal Ca2+ patterns contribute to drug
      actions.

PMID- 12496385
TI  - CD19 function in early and late B cell development: I. Maintenance of follicular
      and marginal zone B cells requires CD19-dependent survival signals.
AB  - Loss of membrane-bound Ig results in the rapid onset of apoptosis in
      recirculating B cells. This observation implies that a competent B cell receptor
      (BCR) is not only required for Ag-dependent differentiation, but also for
      continued survival in the peripheral immune system. Expression of the B cell
      coreceptor, CD19, is likewise essential for key B cell differentiative events
      including the formation of B-1, germinal center, and marginal zone (MZ) B cells.
      In this study, we report that CD19 also exerts a role before Ag encounter by
      promoting the survival of naive recirculating B cells. This aspect of CD19
      signaling was first suggested by the analysis of mixed bone marrow chimeras,
      wherein CD19-/- B cells fail to effectively compete with wild-type B cells to
      reconstitute the peripheral B cell compartment. Consistent with this observation,
      Bromodeoxyuridine- and CFSE-labeling studies reveal a shorter in vivo life span
      for CD19-/- B cells vs their wild-type counterparts. Moreover, we find that CD19
      is necessary for propagation of BCR-induced survival signals and thus may
      contribute to homeostatic mechanisms of tonic signaling. To determine whether
      provision of a constitutive survival signal could compensate for the loss of CD19
      in vivo, Bcl-2-transgenic mice were bred onto the CD19-/- background. Here, we
      observe an increase in follicular B cell numbers and selective recovery of the MZ
      B cell compartment. Together these findings suggest that maintenance of the
      follicular and MZ B cell compartments require CD19-dependent survival signals.

PMID- 12496386
TI  - Impaired antibody response to group B streptococcal type III capsular
      polysaccharide in C3- and complement receptor 2-deficient mice.
AB  - Group B Streptococcus (GBS) is the foremost bacterial cause of serious neonatal
      infections. Protective immunity to GBS is mediated by specific Abs to the
      organism's capsular polysaccharide Ags. To examine the role of complement in the
      humoral immune response to type III GBS capsular polysaccharide (III-PS), mice
      deficient in C3 or in CD21/CD35 (i.e., complement receptors 1 and 2; CR1/CR2)
      were immunized with III-PS. Mice deficient in C3 or Cr2 had an impaired primary
      immune response to III-PS. The defective response was characterized by low IgM
      levels and the lack of an isotype switch from IgM to IgG Ab production. Compared
      with wild-type mice, C3- and Cr2-deficient mice exhibited decreased uptake of III
      PS by follicular dendritic cells within the germinal centers and impaired
      localization of III-PS to the marginal zone B cells. Complement-dependent uptake
      of capsular polysaccharide by marginal zone B cells appears necessary for an
      effective immune response to III-PS. The normal immune response in wild-type mice
      may require localization of polysaccharide to marginal zone B cells with
      subsequent transfer of the Ag to follicular dendritic cells.

PMID- 12496387
TI  - Established T cell-driven germinal center B cell proliferation is independent of
      CD28 signaling but is tightly regulated through CTLA-4.
AB  - CD4 T cell activation is positively (CD28) and negatively (CTLA-4) regulated by
      the costimulatory ligands CD80 and CD86. A central question is how the balance
      between these two opposing forces is controlled as T cells differentiate. We have
      previously shown that CD28 signaling is absolutely required to prime naive CD4 T
      cells to differentiate into effectors that provide help for germinal centers and
      class-switched Ab responses. In this study, we show that the requirement for CD28
      signaling is transient and effector CD4 T cells do not require CD28 signals to
      sustain their function. The CD28 independence of effector T cells within germinal
      centers suggested that a key function for CD80/CD86 under these circumstances
      might be to provide negative regulatory signals via the CD28 homologue CTLA-4. By
      examining germinal center responses in mice where the ability to signal through T
      cell CTLA-4 was compromised, we provide data that supports a critical role for
      CTLA-4 in down-regulating T cell help for germinal center B cells.

PMID- 12496388
TI  - OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires
      CD40-Apc signaling to boost the host T cell antitumor response.
AB  - Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine
      colon carcinoma is not sufficient to cure metastases in a therapeutic setting. To
      determine whether a cellular vaccine that interacts directly with both APC and T
      cells in vivo might be superior, we generated C26 carcinoma cells transduced with
      the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX40L) or
      together with GM-CSF (C26/GM/OX40L), which is known to activate APC. Mice
      injected with C26/OX40L cells displayed only a delay in tumor growth, while the
      C26/GM/OX40L tumor regressed in 85% of mice. Tumor rejection required
      granulocytes, CD4+, CD8+ T cells, and APC-mediated CD40-CD40 ligand cosignaling,
      but not IFN-gamma or IL-12 as shown using subset-depleted and knockout (KO) mice.
      CD40KO mice primed with C26/GM/OX40L cells failed to mount a CTL response, and T
      cells infiltrating the C26/GM/OX40L tumor were OX40 negative, suggesting an
      impairment in APC-T cell cross-talk in CD40KO mice. Indeed, CD4+ T cell-depleted
      mice failed to mount any CTL activity against the C26 tumor, while treatment with
      agonistic mAb to CD40, which acts on APC, bypassed the requirement for CD4+ T
      cells and restored CTL activation. C26/GM/OX40L cells cured 83% of mice bearing
      lung metastases, whereas C26/OX40L or C26/GM vaccination cured only 28 and 16% of
      mice, respectively. These results indicate the synergistic activity of OX40L and
      GM-CSF in a therapeutic setting.

PMID- 12496389
TI  - Innate immunity mediated by the cytokine IL-1 homologue 4 (IL-1H4/IL-1F7) induces
      IL-12-dependent adaptive and profound antitumor immunity.
AB  - Recently, several novel members of the IL-1 family have been identified. The
      possible therapeutic utility and the underlying biologic role of these new
      members remain unclear. In the present study we analyzed the anti-tumor activity
      of human IL-1 homologue 4(IL-1H4; renamed IL-F7) by adenovirus-mediated gene
      transfer (AdIL-1H4) directly into murine tumors. In vitro expression analysis
      showed that IL-1H4 was a secretory protein. Treatment of an established MCA205
      mouse fibrosarcoma by single intratumoral injection of AdIL-1H4 resulted in
      significant growth suppression. Furthermore, complete inhibition of tumor growth
      was observed following multiple injections of AdIL-1H4. The anti-tumor activity
      of IL-1H4 was abrogated in nude and SCID mice and in IL-12-, IFN-gamma-, or Fas
      ligand-deficient mice. In contrast, IL-1H4 was able to confer substantial anti
      tumor effects in NKT-deficient mice. These results suggest that IL-1H4 could play
      an important role in the link between innate and adaptive immunity and may be
      useful for tumor immunotherapy.

PMID- 12496390
TI  - Interaction of the estrogen receptors with the Fas ligand promoter in human
      monocytes.
AB  - The predominance of autoimmune diseases among women suggests that estrogen may
      modulate immune function. Monocytes and macrophages are important in initiating,
      maintaining, and resolving inflammatory responses through cell-signaling
      molecules, which control immune cell survival. One important mechanism of cell
      survival is mediated by the Fas/Fas ligand (FasL) system. In this study, the link
      between estrogen, monocytes/macrophages, and the Fas/FasL system was
      investigated. Estrogen treatment increased FasL expression in monocytes through
      the binding of the estrogen receptors (ER) to the estrogen recognizing elements
      and AP-1 motifs present at the FasL promoter. Furthermore, estrogen induced
      apoptosis in monocytes expressing ERbeta, but not in monocyte-differentiated
      macrophages expressing ERalpha. The expression of either ERalpha or ERbeta and
      their response to estrogen in monocytes was found to be dependent on the their
      stage of cell differentiation. Previously, we have shown that estrogen
      replacement therapy in postmenopausal women decreased the number of circulating
      monocytes. In this study, we have characterized the molecular mechanism by which
      estrogen regulates monocytes homeostasis. These findings indicate that estrogen
      may regulate immune cell survival through the Fas/FasL system. There is
      biological relevance to these findings in view of studies showing that
      accumulation of activated monocytes is involved in the pathogenesis of conditions
      such as vasculititis, arteriosclerosis, and rheumatoid arthritis.

PMID- 12496391
TI  - Detection of low-avidity CD4+ T cells using recombinant artificial APC: following
      the antiovalbumin immune response.
AB  - Subtle differences oppose CD4+ to CD8+ T cell physiologies that lead to different
      arrays of effector functions. Interestingly, this dichotomy has also unexpected
      practical consequences such as the inefficacy of many MHC class II tetramers in
      detecting specific CD4+ T cells. As a mean to study the CD4+ anti-OVA response in
      H-2(d) and H-2(b) genetic backgrounds, we developed I-A(d)- and I-A(b)-OVA
      recombinant MHC monomers and tetramers. We were able to show that in this
      particular system, despite normal biological activity, MHC class II tetramers
      failed to stain specific T cells. This failure was shown to be associated with a
      lack of cooperation between binding sites within the tetramer as measured by
      surface plasmon resonance. This limited cooperativeness translated into a low
      "functional avidity" and very transient binding of the tetramers to T cells. To
      overcome this biophysical barrier, recombinant artificial APC that display MHC
      molecules in a lipid bilayer were developed. The plasticity and size of the MHC
      bearing fluorescent liposomes allowed binding to Ag-specific T cells and the
      detection of low numbers of anti-OVA T cells following immunization. The same
      liposomes were able, at 37 degrees C, to induce the full reorganization of the T
      cell signaling molecules and the formation of an immunological synapse.
      Artificial APC will allow T cell detection and the dissection of the molecular
      events of T cell activation and will help us understand the fundamental
      differences between CD4+ and CD8+ T cells.

PMID- 12496392
TI  - A novel polymorphic CAAT/enhancer-binding protein beta element in the FasL gene
      promoter alters Fas ligand expression: a candidate background gene in African
      American systemic lupus erythematosus patients.
AB  - A single-nucleotide polymorphism (SNP), identified at nucleotide position -844 in
      the 5' promoter of the FasL gene, lies within a putative binding motif for
      CAAT/enhancer-binding protein beta (C/EBPbeta). Electrophoretic mobility shift
      and supershift assays confirmed that this element binds specifically to C/EBPbeta
      and demonstrated that the two alleles of this element have different affinities
      for C/EBPbeta. In luciferase reporter assays, the -844C genotype had twice the
      basal activity of the -844T construct, and basal expression of Fas ligand (FasL)
      on peripheral blood fibrocytes was also significantly higher in -844C than in 
      844T homozygous donors. FasL is located on human chromosome 1q23, a region that
      shows linkage to the systemic lupus autoimmune phenotype. Analysis of 211 African
      American systemic lupus erythematosus patients revealed enrichment of the -844C
      homozygous genotype in these systemic lupus erythematosus patients compared with
      150 ethnically matched normal controls (p = 0.024). The -844C homozygous genotype
      may lead to the increased expression of FasL, to altered FasL-mediated signaling
      in lymphocytes, and to enhanced risk for autoimmunity. This functionally
      significant SNP demonstrates the potential importance of SNPs in regulatory
      regions and suggests that differences in the regulation of FasL expression may
      contribute to the development of the autoimmune phenotype.

PMID- 12496393
TI  - Prostaglandins inhibit 5-lipoxygenase-activating protein expression and
      leukotriene B4 production from dendritic cells via an IL-10-dependent mechanism.
AB  - PGs produced from arachidonic acid by the action of cyclooxygenase enzymes play a
      pivotal role in the regulation of both inflammatory and immune responses. Because
      leukotriene B4 (LTB4), a product of 5-lipoxygenase (5-LO) pathway, can exert
      numerous immunoregulatory and proinflammatory activities, we examined the effects
      of PGs on LTB4 release from dendritic cells (DC) and from peritoneal macrophages.
      In concentration-dependent manner, PGE1 and PGE2 inhibited the production of LTB4
      from DC, but not from peritoneal macrophage, with an IC50 of 0.04 microM. The
      same effect was observed with MK-886, a 5-LO-activating protein (FLAP)-specific
      inhibitor. The decreased release of LTB4 was associated with an enhanced level of
      IL-10. Furthermore, the inhibition of LTB4 synthesis by PGs was significantly
      reversed by anti-IL-10, suggesting the involvement of an IL-10-dependent
      mechanism. Hence, we examined the effects of exogenous IL-10 on the 5-LO pathway.
      We demonstrate that IL-10 suppresses the production of LTB4 from DC by inhibiting
      FLAP protein expression without any effect on 5-LO and cytosolic phospholipase
      A2. Taken together, our results suggest links between DC cyclooxygenase and 5-LO
      pathways during the inflammatory response, and FLAP is a key target for the PG
      induced IL-10-suppressive effects.

PMID- 12496394
TI  - Induction of telomerase activity and maintenance of telomere length in virus
      specific effector and memory CD8+ T cells.
AB  - Acute viral infections induce extensive proliferation and differentiation of
      virus-specific CD8+ T cells. One mechanism reported to regulate the proliferative
      capacity of activated lymphocytes is mediated by the effect of telomerase in
      maintaining the length of telomeres in proliferating cells. We examined the
      regulation of telomerase activity and telomere length in naive CD8+ T cells and
      in virus-specific CD8+ T cells isolated from mice infected with lymphocytic
      choriomeningitis virus. These studies reveal that, compared with naive CD8+ T
      cells, which express little or no telomerase activity, Ag-specific effector and
      long-lived memory CD8+ T cells express high levels of telomerase activity.
      Despite the extensive clonal expansion that occurs during acute lymphocytic
      choriomeningitis virus infection, telomere length is maintained in both effector
      and memory CD8+ T cells. These results suggest that induction of telomerase
      activity in Ag-specific effector and memory CD8+ T cells is important for the
      extensive clonal expansion of both primary and secondary effector cells and for
      the maintenance and longevity of the memory CD8+ T cell population.

PMID- 12496395
TI  - Human gamma delta-T lymphocytes express and synthesize connective tissue growth
      factor: effect of IL-15 and TGF-beta 1 and comparison with alpha beta-T
      lymphocytes.
AB  - T lymphocytes bearing the gammadelta-TCR accumulate during wound healing and
      inflammation. However, the role of gammadelta-T lymphocytes in fibrogenic tissue
      reactions is not well understood. Therefore, we addressed the question of whether
      human gammadelta-T cells express and synthesize connective tissue growth factor
      (CTGF), a factor known to regulate fibrogenesis and wound healing. In addition,
      the lymphoblastic leukemia T cell line (Loucy) that possesses characteristics
      typical of gammadelta-T cells was used as a model to evaluate the regulation of
      CTGF gene expression. Blood gammadelta-T cells isolated from healthy donors were
      grown in the presence of IL-15/TGF-beta1 for 48 h and assessed for the expression
      and synthesis of CTGF. Nonstimulated human blood gammadelta-T cells and Loucy
      gammadelta-T cells expressed low levels of CTGF mRNA. Costimulation of the cells
      with IL-15 and TGF-beta1 resulted in a substantially increased level of CTGF mRNA
      expression within 4-8 h, and it remained elevated for at least 48 h. In contrast,
      no CTGF mRNA was detected when nonstimulated and stimulated human CD4+ alphabeta
      T cells were analyzed. In addition, Western blot analysis of human gammadelta-T
      cell lysates prepared 4 days following stimulation with IL-15 and TGF-beta1
      revealed a 38-kDa CTGF protein in cell lysates of human gammadelta-T cells.
      Detection was confirmed using Colo 849 fibroblasts, which can constitutively
      express high levels of CTGF. In conclusion, we herein present novel evidence that
      in contrast to CD4+ alphabeta-T cells human gammadelta-T cells are capable of
      expressing CTGF mRNA and synthesizing its corresponding protein, which supports
      the concept that gammadelta-T cells may contribute to wound healing or tissue
      fibrotic processes.

PMID- 12496396
TI  - Critical paracrine interactions between TNF-alpha and IL-10 regulate
      lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E2
      production.
AB  - Increased production of PGs by gestational membranes is believed to be a
      principal initiator of term and preterm labor. Intrauterine infection is
      associated with an inflammatory response in the choriodecidua characterized by
      elevated production of cytokines and PGs. The precise physiological significance
      of enhanced choriodecidual cytokine production in the mechanism of preterm labor
      remains uncertain. These studies were undertaken to dissect the roles and
      regulation of endogenous cytokines in regulating PG production by human
      choriodecidua. We used LPS treatment of human choriodecidual explants as our
      model system. In choriodecidual explant cultures, LPS (5 microg/ml) induced a
      rapid increase in TNF-alpha production, peaking at 4 h. In contrast, IL-10, IL
      1beta, and PGE2 production rates peaked 8, 12, and 24 h, respectively, after LPS
      stimulation. Immunoneutralization studies indicated that TNF-alpha was a primary
      regulator of IL-1beta, IL-10, and PGE2 production, while IL-1beta stimulated only
      PGE2 production. Neutralization of endogenous IL-10 resulted in increased TNF
      alpha and PGE2 production. IL-10 treatment markedly decreased TNF-alpha and IL
      1beta production, but had no effect on PGE2 production. Taken together, these
      results demonstrate that the effects of LPS on choriodecidual cytokine and PG
      production are modulated by both positive and negative feedback loops. In the
      setting of an infection of the intrauterine, TNF-alpha may be a potential target
      for treatment intervention; IL-10 could be one such therapeutic.

PMID- 12496397
TI  - Differential expression of platelet-activating factor acetylhydrolase in
      macrophages and monocyte-derived dendritic cells.
AB  - Although macrophages (Mphi) and monocyte-derived dendritic cells (MDDC) come from
      a common precursor, they are distinct cell types. This report compares the two
      cell types with respect to the metabolism of platelet-activating factor (PAF), a
      biologically active lipid mediator. These experiments were prompted by our
      studies of localized juvenile periodontitis, a disease associated with high IgG2
      production and a propensity of monocytes to differentiate into MDDC. As the IgG2
      Ab response is dependent on PAF, and MDDC selectively induce IgG2 production, we
      predicted that PAF levels would be higher in MDDC than in Mphi. To test this
      hypothesis, human MDDC were prepared by treating adherent monocytes with IL-4 and
      GM-CSF, and Mphi were produced by culture in M-CSF. Both Mphi and MDDC
      synthesized PAF; however, MDDC accumulated significantly more of this lipid. We
      considered the possibility that PAF accumulation in MDDC might result from
      reduced turnover due to lower levels of PAF acetylhydrolase (PAFAH), the enzyme
      that catabolizes PAF. Although PAFAH increased when monocytes differentiated into
      either cell type, MDDC contained significantly less PAFAH than did Mphi and
      secreted almost no PAFAH activity. The reduced levels of PAFAH in MDDC could be
      attributed to lower levels of expression of the enzyme in MDDC and allowed these
      cells to produce PGE(2) in response to exogenous PAF. In contrast, Mphi did not
      respond in this manner. Together, these data indicate that PAF metabolism may
      impinge on regulation of the immune response by regulating the accessory activity
      of MDDC.

PMID- 12496398
TI  - High avidity CD8+ T cells are the initial population elicited following viral
      infection of the respiratory tract.
AB  - Following intranasal administration, the model paramyxovirus simian virus 5 (SV5)
      establishes an infection in the respiratory tract of mice, which is subsequently
      cleared by CD8+ T cells. In this study, we sought to understand the maturation of
      the antiviral immune response over time by assessing the functional avidity of
      the responding T cells and the expansion of immunodominant populations.
      Surprisingly, we determined that the initial response to Ag at day 3 (d3) in the
      mediastinal lymph node was exclusively high avidity. However, by d5
      postinfection, low avidity cells were approximately 50% of the responding T cell
      population. Following secondary exposure to SV5, high avidity CD8+ T cells again
      are the exclusive cell type present at early times postinfection (d2). Similarly,
      high avidity cells were preferentially elicited at d3 following infection with
      the unrelated vaccinia virus. We also made the observation that the
      immunodominance profile has not been established at d3 postinfection with SV5.
      However, by d5 a clear immunodominance pattern arises and is permanently
      maintained. These data indicate that high avidity cells are the predominant
      population responding at early times postinfection following respiratory
      infection with SV5 or vaccinia virus. However, as the response progresses, low
      avidity cells are activated/expanded to a greater extent compared with high
      avidity cells.

PMID- 12496399
TI  - Models for antigen receptor gene rearrangement. III. Heavy and light chain
      allelic exclusion.
AB  - The extent of allelic exclusion in Ig genes is very high, although not absolute.
      Thus far, it has not been clearly established whether rapid selection of the
      developing B cell as soon as it has achieved the first productively rearranged,
      functional heavy chain is the only mechanism responsible for allelic exclusion.
      Our computational models of Ag receptor gene rearrangement in B lymphocytes are
      hereby extended to calculate the expected fractions of heavy chain allelically
      included newly generated B cells as a function of the probability of heavy chain
      pairing with the surrogate light chain, and the probability that the cell would
      test this pairing immediately after the first rearrangement. The expected
      fractions for most values of these probabilities significantly exceed the levels
      of allelic inclusion in peripheral B cells, implying that in most cases
      productive rearrangement and subsequent cell surface expression of one allele of
      the heavy chain gene probably leads to prevention of rearrangement completion on
      the other allele, and that additional mechanisms, such as peripheral selection
      disfavoring cells with two productively rearranged heavy chain genes, may also
      play a role. Furthermore, we revisit light chain allelic exclusion by utilizing
      the first (to our knowledge) computational model which addresses and enumerates B
      cells maturing with two productively rearranged kappa light chain genes. We show
      that, assuming that there are no selection mechanisms responsible for abolishing
      cells expressing two light chains, the repertoire of newly generated B
      lymphocytes exiting the bone marrow must contain a significant fraction of such
      kappa double-productive B cells.

PMID- 12496400
TI  - Toll-like receptor 2 ligands as adjuvants for human Th1 responses.
AB  - Bacterial lipopeptides (bLPs) are increasingly used as adjuvants to activate cell
      mediated immune responses to foreign Ags. To explore mechanisms whereby bLPs
      adjuvant T cell responses, we stimulated human PBMCs with bLPs. We found that
      bLPs stimulate T cells to proliferate and produce IFN-gamma in an accessory cell
      dependent manner and in the absence of exogenous protein Ags. The ability of bLPs
      to stimulate T cell proliferation was Toll-like receptor 2 dependent and required
      IL-12, interaction with costimulatory molecules, and MHC proteins. Our data
      suggest that bLPs adjuvant adaptive Th1 responses by enhancing Ag presentation of
      endogenous peptides.

PMID- 12496401
TI  - Self-specific MHC class II-restricted CD4-CD8- T cells that escape deletion and
      lack regulatory activity.
AB  - In the presence of the I-Ealpha protein, transgenic (Tg) mice expressing the
      1H3.1 alphabeta TCR that is specific for the Ealpha52-68:I-A(b) complex display
      drastic intrathymic deletion. Although peripheral T cells from these mice
      remained unresponsive to the Ealpha52-68:I-A(b) complex, they contained a
      subpopulation able to specifically react to this complex in the presence of
      exogenous IL-2, indicating that some 1H3.1 alphabeta TCR Tg T cells have escaped
      clonal deletion and efficiently populated the periphery. IL-2-dependent, Ealpha52
      68:I-A(b) complex-responsive T cells were CD4-CD8- and expressed the 1H3.1
      alphabeta TCR. Such T cells could develop intrathymically, did not show sign of
      regulatory/suppressor activity, displayed a typical naive phenotype, and seemed
      to persist in vivo over time. CD4-CD8- TCR Tg T cells were also detected when the
      surface density of the deleting ligand was increased on MHC class II+ cells. In
      addition, the development of CD4-CD8- 1H3.1 alphabeta TCR Tg T cells could be
      supported by I-A(b) molecules. These observations indicate that CD4 surface
      expression neither specifies, nor is required for, the thymic export of mature
      thymocytes expressing a MHC class II-restricted alphabeta TCR. The data also show
      that, although the avidity of the interaction involved in intrathymic deletion is
      significantly lower than that involved in mature T cell activation, its range can
      be large enough to be influenced by the presence or absence of coreceptors.
      Finally, the margin created by the absence of CD4 coreceptor was substantial
      because it could accommodate various amounts of the deleting ligand on thymic
      stromal cells.

PMID- 12496402
TI  - A role for Stat5 in CD8+ T cell homeostasis.
AB  - Cytokine signals are known to contribute to CD8+ memory T cell homeostasis, but
      an exact understanding of the mechanism(s) has remained elusive. We have now
      investigated the role of Stat5 proteins in this process. Whereas Stat5a and
      Stat5b KO mice have decreased numbers of CD8+ T cells, Stat5-transgenic mice have
      an increased number of these cells. Stat5b-transgenic mice exhibit increased Ag
      induced cell death of CD4+ T cells and augmented proliferation and Bcl-2
      expression in CD8+ T cells, providing a basis for this finding. Moreover, CD8+
      memory T cells are substantially affected by Stat5 levels. These findings
      identify Stat5 proteins as critical signaling mediators used by cytokines to
      regulate CD8+ T cell homeostasis.

PMID- 12496403
TI  - Regulation of mouse mammary tumor virus env transcriptional activator initiated
      mammary tumor virus superantigen transcripts in lymphomas of SJL/J mice: role of
      Ikaros, demethylation, and chromatin structural change in the transcriptional
      activation of mammary tumor virus superantigen.
AB  - Mammary tumor virus (Mtv29)-encoded superantigen expressed by SJL/J mouse B cell
      lymphomas stimulates CD4+V16+ T cells and thereby acquires T cell help necessary
      for lymphoma growth. Mtv29 mouse mammary tumor virus env transcriptional
      activator (META) env-controlled Mtv29 superantigen (vSAg29) mRNA transcripts (1.8
      kb) are not expressed in normal B or other somatic cells. Real-time PCR-based
      assays with DNA from normal SJL liver and vSAg29- lymphoma (cNJ101), digested
      with methylation-sensitive enzymes, showed hypermethylation at AvaI, FspI, HpaII,
      ThaI, and the distal HgaI sites of the META env, but vSAg29+ lymphoma cells
      showed significant demethylation at AvaI, HpaII, and the distal HgaI sites. The
      distal HgaI site that is adjacent to an Ikaros binding site is significantly
      demethylated in the META env DNA from primary lymphomas. Gel shift assays showed
      binding of Ikaros to a sequence representing this region in the META env. SJL
      lymphomas expressed the Ikaros isoform Ik6 that was absent in normal B cells.
      vSAg29+ cells exhibited increased DNaseI accessibility to chromatin at the vSAg29
      initiation site. Treatment of cNJ101 cells with a demethylating agent, 5
      azacytidine, and a histone deacetylase inhibitor, trichostatin A, caused
      hypomethylation at AvaI, HpaII, and distal HgaI sites and led to chromatin
      structural change at the vSAg29 initiation site, accompanied by the expression of
      vSAg29 transcripts. This enabled cNJ101 cells to stimulate SJL lymphoma
      responsive CD4+V16+ T hybridoma cells. Thus, demethylation at the distal HgaI
      site of the Mtv29 META env permits vSAg29 expression, which may have an impact on
      the development of germinal center-derived B cell lymphomas of SJL/J mice.

PMID- 12496404
TI  - In vivo augmentation of tumor-specific CTL responses by class I/peptide antigen
      complexes on microspheres (large multivalent immunogen).
AB  - Tumor membrane Ag immobilized on cell size microspheres (large multivalent
      immunogen (LMI)) was previously shown to augment tumor-specific CTL activity and
      reduce tumor growth, and a clinical trial examining this approach is in progress.
      In the current study, LMI treatment has been examined using adoptive transfer of
      TCR-transgenic CD8 T cells to visualize Ag-specific cells during the response. OT
      I T cells specific for H-2K(b)/OVA(257-264) were transferred into mice that were
      then challenged with LMI made by immobilizing H-2K(b)/OVA(257-264) on
      microspheres (K(b)/OVA(257-264)-LMI) alone, or along with i.p. challenge with OVA
      expressing E.G7 tumor. K(b)/OVA(257-264)-LMI caused significant reduction of
      tumor growth when administered to E.G7-bearing mice. When administered alone, the
      K(b)/OVA(257-264)-LMI caused only weak clonal expansion of OT-I cells in the
      spleen and lymph nodes, although most of the OT-I cells up-regulated expression
      of CD44 and VLA-4. In contrast, K(b)/OVA(257-264)-LMI administration to E.G7
      bearing mice stimulated no detectable expansion of OT-I cells in the spleen and
      lymph nodes but caused a rapid increase in the number of OT-I cells in the
      peritoneal cavity, the site of the growing tumor. These results demonstrate the
      potential for using class I/tumor peptide complexes for immunotherapy. In
      addition, they suggest a model for the mechanism of CTL augmentation in which
      recognition of the LMI Ag results in altered trafficking of the tumor-specific
      CD8 T cells so that they reach the site of a growing tumor more rapidly and in
      greater numbers, where they may further expand and acquire effector function.

PMID- 12496405
TI  - Efficient induction of primary and secondary T cell-dependent immune responses in
      vivo in the absence of functional IL-2 and IL-15 receptors.
AB  - IL-2 and IL-15 are thought to be important cytokines for T cell-dependent immune
      responses. Mice deficient in IL-2, IL-2Ralpha, and IL-2Rbeta are each
      characterized by a rapid lethal autoimmune lymphoproliferative disorder that
      complicates their use in studies aimed at investigating the role of these
      cytokines and receptors for immune responses in vivo. We have previously
      characterized a novel transgenic (Tg) mouse on the IL-2Rbeta-/- genetic
      background (Tg-/- mice) that lacks autoimmune disease but still contains
      peripheral T cells that are nonresponsive to IL-2 and IL-15. In the present
      study, these mice were used to investigate the extent by which IL-2 and IL-15 are
      essential for T cell immunity in vivo. Tg-/- mice generated near normal primary
      and secondary Ab responses to OVA, readily mounted first and second set
      allogeneic skin graft rejection responses, and developed primary and recall CD8 T
      cell responses to vaccinia virus. However, Tg-/- mice generated a slightly lower
      level of IgG2a Abs to OVA, exhibited a somewhat delayed first set skin graft
      rejection response with lower allo-specific CTL, and developed a significantly
      lower number of IFN-gamma-producing vaccinia-specific CD8+ T cells. Thus,
      although T effector function is somewhat impaired, T cell immunity is largely
      functional in the absence of IL-2- and IL-15-induced signaling through IL-2Rbeta.

PMID- 12496406
TI  - A gammaherpesvirus G protein-coupled receptor homologue is required for increased
      viral replication in response to chemokines and efficient reactivation from
      latency.
AB  - The open reading frame (ORF) 74 of gamma-2-herpesviruses encodes a G protein
      coupled receptor which is highly conserved in members of this subfamily and is
      homologous to the CXCR2 chemokine receptor. The viral G protein-coupled receptor
      has been implicated in viral pathogenesis. However, the advantage of such
      chemokine receptor homologues to the virus is currently unknown. To address this,
      we constructed ORF74 deletion mutants of a mouse gamma-2-herpesvirus (MHV-68) and
      examined the effect of the deletion on viral growth and reactivation from
      latency. Growth of the mutant viruses in NIH 3T3 cells was similar to that of
      wild-type virus. However, CXC chemokines with ELR motifs, KC, and macrophage
      inflammatory protein 2, significantly increased viral replication of the wild
      type, but not the mutant viruses, via a pertussis toxin-insensitive, mitogen
      activated protein/extracellular signal-regulated kinase and phosphatidylinositol
      3-kinase-dependent pathway. IFN-gamma-inducible protein 10, a CXC chemokine
      lacking an ELR motif, was able to reverse the effect of KC on viral replication.
      The mutant viruses also showed significantly reduced reactivation from latently
      infected mouse splenocytes. Reinsertion of ORF74 into the mutant virus restored
      the wild-type phenotype. Utilizing a viral CXCR2 homologue to enhance replication
      and reactivation from latency represents a novel mechanism by which
      gammaherpesviruses can subvert the immune response.

PMID- 12496407
TI  - Pre-B cell antigen receptor-mediated signal inhibits CD24-induced apoptosis in
      human pre-B cells.
AB  - We previously reported that the cross-linking of cluster of differentiation
      (CD)24 induces apoptosis in Burkitt's lymphoma cells and that this phenomenon can
      be enhanced by a B cell Ag receptor (BCR)-mediated signal. In this study, we
      extend our previous observation and report that CD24 also mediated apoptosis in
      human precursor-B acute lymphoblastic leukemia cell lines in the pro-B and pre-B
      stages accompanying activation of multiple caspases. Interestingly, simultaneous
      cross-linking of pre-BCR clearly inhibited CD24-mediated apoptosis in pre-B
      cells. We also observed that mitogen-activated protein kinases (MAPKs) were
      involved in the regulation of this apoptotic process. Pre-BCR cross-linking
      induced prompt and strong activation of extracellular signal-regulated kinase 1,
      whereas CD24 cross-linking induced the sustained activation of p38 MAPK,
      following weak extracellular signal-regulated kinase 1 activation. SC68376, a
      specific inhibitor of p38 MAPK, inhibited apoptosis induction by CD24 cross
      linking, whereas anisomycin, an activator of p38 MAPK, enhanced the apoptosis. In
      addition, PD98059, a specific inhibitor of MEK-1, enhanced apoptosis induction by
      CD24 cross-linking and reduced the antiapoptotic effects of pre-BCR cross
      linking. Collectively, whether pre-B cells survive or die may be determined by
      the magnitude of MAPK activation, which is regulated by cell surface molecules.
      Our findings should be important to understanding the role of CD24-mediated cell
      signaling in early B cell development.

PMID- 12496408
TI  - A division-linked mechanism for the rapid generation of Ig-secreting cells from
      human memory B cells.
AB  - Memory B cells, when re-exposed to Ag and T cell help, differentiate into Ig
      secreting cells (ISC) at the same time as maintaining a residual pool of non-Ig
      secreting cells with memory capabilities. To investigate the mechanism underlying
      this dual process, we followed the fate of human B cells activated in vitro with
      the T cell-derived signals CD40 ligand (CD40L), IL-2, and IL-10 using CFSE to
      monitor cell division. A substantial number of ISCs detected by ELISPOT,
      intracellular Ig staining, and Ig secretion could be generated from memory but
      not naive B cells. The proportion of ISCs increased with successive cell
      divisions and was markedly enhanced by IL-10 at each division. Within ISCs, two
      distinct populations were detected after withdrawal of CD40L. The first had
      acquired the plasma cell marker CD38 and continued to proliferate despite the
      absence of CD40L. In contrast, the second population remained CD38(-), ceased
      dividing, and underwent rapid apoptosis. The former most likely represent the
      immediate precursors of long-lived plasma cells, which preferentially home to the
      bone marrow in vivo, whereas the latter contain short-lived ISCs responsible for
      the initial Ab response to stimulation with Ag and T cell help. Taken together,
      the results point to a division-based mechanism responsible not only for
      regulating differentiation of short- and long-lived ISCs from memory B cells, but
      for preserving the memory B cell pool for reactivation upon subsequent Ag
      exposure.

PMID- 12496409
TI  - IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice.
AB  - We previously demonstrated that a specialized subset of immature myeloid cells
      migrate to lymphoid organs as a result of tumor growth or immune stress, where
      they suppress B and T cell responses to Ags. Although NO was required for
      suppression of mitogen activation of T cells by myeloid suppressor cells (MSC),
      it was not required for suppression of allogenic responses. In this study, we
      describe a novel mechanism used by MSC to block T cell proliferation and CTL
      generation in response to alloantigen, which is mediated by the enzyme arginase 1
      (Arg1). We show that Arg1 increases superoxide production in myeloid cells
      through a pathway that likely utilizes the reductase domain of inducible NO
      synthase (iNOS), and that superoxide is required for Arg1-dependent suppression
      of T cell function. Arg1 is induced by IL-4 in freshly isolated MSC or cloned MSC
      lines, and is therefore up-regulated by activated Th2, but not Th1, cells. In
      contrast, iNOS is induced by IFN-gamma and Th1 cells. Because Arg1 and iNOS share
      L-arginine as a common substrate, our results indicate that L-arginine metabolism
      in myeloid cells is a potential target for selective intervention in reversing
      myeloid-induced dysfunction in tumor-bearing hosts.

PMID- 12496410
TI  - CD25+ immunoregulatory CD4 T cells mediate acquired central transplantation
      tolerance.
AB  - Transplantation tolerance is induced reliably in experimental animals following
      intrathymic inoculation with the relevant donor strain Ags; however, the
      immunological mechanisms responsible for the induction and maintenance of the
      tolerant state remain unknown. We investigated these mechanisms using TCR
      transgenic mice (TS1) that carry T cells specific for an immunodominant, MHC
      class II-restricted peptide (S1) of the influenza PR8 hemagglutinin (HA)
      molecule. We demonstrated that TS1 mice reject skin grafts that have transgene
      encoded HA molecules (HA104) as their sole antigenic disparity and that
      intrathymic but not i.v. inoculation of TS1 mice with S1 peptide induces
      tolerance to HA-expressing skin grafts. Intrathymic peptide inoculation was
      associated with a dose-dependent reduction in T cells bearing high levels of TCR
      specific for HA. However, this reduction was both incomplete and transient, with
      a full recovery of S1-specific thymocytes by 4 wk. Peptide inoculation into the
      thymus also resulted in the generation of immunoregulatory T cells (CD4+CD25+)
      that migrated to the peripheral lymphoid organs. Adoptive transfer experiments
      using FACS sorted CD4+CD25- and CD4+CD25+ T cells from tolerant mice revealed
      that the former but not the latter maintain the capacity to induce rejection of
      HA bearing skin allografts in syngeneic hosts. Our results suggest that both
      clonal frequency reduction in the thymus and immunoregulatory T cells exported
      from the thymus are critical to transplantation tolerance induced by intrathymic
      Ag inoculation.

PMID- 12496411
TI  - Inhibition of calpain is a component of nitric oxide-induced down-regulation of
      human mast cell adhesion.
AB  - Nitric oxide is an important messenger that regulates mast cell activity by
      modifications to gene expression and intracellular pathways associated with
      exocytosis and adhesion. Integrin interactions with extracellular matrix
      components modulate an array of cell activities, including mediator production
      and secretion. To investigate the molecular mechanisms underlying NO regulation
      of mast cell function, we studied its effects on adhesion of a human mast cell
      line (HMC-1) to fibronectin (FN). The NO donors S-nitrosoglutathione and S
      nitroso-N-acetylpenicillamine strongly down-regulated the adhesion of HMC-1 to
      FN. Inhibitors of soluble guanylate cyclase and protein kinase G did not alter
      the response of cells to NO. A peroxynitrite scavenger did not affect modulation
      of adhesion by NO, nor could the effect of NO be mimicked by the peroxynitrite
      producing compound 3-morpholinosydnonimine. NO donors inhibited the cysteine
      protease, calpain, while calpain inhibitors mimicked the effect of NO and led to
      a decrease in the ability of HMC-1 cells to adhere to FN. Thus, NO is an
      effective down-regulator of human mast cell adhesion. The mechanism for this
      action does not involve peroxynitrite or activation of soluble guanylate cyclase.
      Instead, a portion of NO-induced down-regulation of adhesion may be attributed to
      inhibition of the cysteine protease, calpain, an enzyme that has been associated
      with control of integrin activation in other cell types. The inhibition of
      calpain is most likely mediated via nitrosylation of its active site thiol group.
      Calpain may represent a novel therapeutic target for the regulation of mast cell
      activity in inflammatory disorders.

PMID- 12496412
TI  - Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target
      cells enhances adhesion of resting NK cells.
AB  - The beta2 integrin LFA-1 (CD11a/CD18) mediates adhesion of lymphocytes to cells
      expressing ICAM. The strength of this adhesion is regulated by different signals
      delivered by cytokines and chemokines, and by the TCR in the case of T cells. To
      determine the receptor-ligand interactions required for adhesion of resting NK
      cells, Drosophila cells expressing different combinations of ligands of human NK
      cell receptors were generated. Expression of ICAM-1 alone was sufficient for an
      adhesion of resting NK cells that was sensitive to inhibitors of src family
      kinase and of phosphatidylinositol 3-kinase. Binding of resting NK cells to solid
      phase ICAM-1 showed similar signaling requirements. A pulse of either IL-2 or IL
      15 to resting NK cells resulted in strongly enhanced, actin-dependent adhesion to
      insect cells expressing ICAM-1 alone. Coexpression of either LFA-3 (CD58) or CD48
      with ICAM-1 resulted in strong adhesion by resting NK cells, even in the absence
      of cytokines. Therefore, receptors for LFA-3 and CD48 on resting NK cells
      strengthen the adhesion mediated by LFA-1.

PMID- 12496413
TI  - Activated STAT4 and a functional role for IL-12 in human Peyer's patches.
AB  - T cells in the Peyer's patches (PP) of the human ileum are exposed to a myriad of
      dietary and bacterial Ags from the gut lumen. Recall proliferative responses to
      common dietary Ags are readily demonstrable by PP T cells from healthy
      individuals, and the cytokine response is dominated by IFN-gamma. Consistent with
      Th1 skewing, PP cells spontaneously secrete IL-12p70, and IL-12p40 protein can be
      visualized underneath the PP dome epithelium. In this study, we have analyzed IL
      12 signaling in PP and investigated whether IL-12 plays a functional role. CD3+ T
      lymphocytes isolated from PP and adjacent ileal mucosa spontaneously secrete IFN
      gamma with negligible IL-4 or IL-5. RNA transcripts for IL-12Rbeta2, the
      signaling component of the IL-12R, are present in purified CD4+ and CD8+ T PP
      lymphocytes. Active STAT4, a transcription factor essential for IL-12-mediated
      Th1 differentiation, is readily detectable in biopsies from PP and ileal mucosa
      and STAT4-DNA binding activity is demonstrable by EMSA. Nuclear proteins from
      CD3+ T PP lymphocytes contain STAT4 and T-bet, a transcription factor selectively
      expressed in Th1 cells. Stimulation of freshly isolated PP cells with
      staphylococcal enterotoxin B dramatically enhanced the production of IFN-gamma,
      an effect which was largely inhibited by neutralizing anti-IL-12 Ab. These data
      show that IL-12 in human PP is likely to be responsible for the Th1-dominated
      cytokine response of the human mucosal immune system.

PMID- 12496414
TI  - Roles of vasoactive intestinal peptide (VIP) in the expression of different
      immune phenotypes by wild-type mice and T cell-targeted type II VIP receptor
      transgenic mice.
AB  - Vasoactive intestinal peptide (VIP) and its two G protein-coupled receptors,
      VPAC1 and VPAC2, are quantitatively prominent and functionally critical in the
      immune system. Transgenic (T) mice constitutively expressing VPAC2 selectively in
      CD4 T cells, at levels higher than those found after maximal induction in CD4 T
      cells of wild-type (N) mice, have elevated blood concentrations of IgE, IgG1, and
      eosinophils; enhanced immediate-type hypersensitivity; and reduced delayed-type
      hypersensitivity. In contrast, VPAC2-null (K) mice manifest decreased immediate
      type hypersensitivity and enhanced delayed-type hypersensitivity. The phenotypes
      are attributable to opposite skewing of the Th2/Th1 cytokine ratio, but no
      studies were conducted on the roles of T cell-derived VIP and altered expansion
      of the Th subsets. Dependence of the Th phenotype of T mice, but not of N or K
      mice, on T cell-derived VIP now is proven by showing that eliminating VIP from
      TCR-stimulated T cell cultures with VIPase IgG normalizes the elevated number of
      IL-4-secreting CD4 T cells, decreases the secretion of IL-4 and IL-10, and
      increases the secretion of IFN-gamma. Flexible responsiveness of CD4 T cells from
      N and K mice, but not T mice, to exogenous VIP in vitro and in vivo is shown by
      increased numbers of IL-4-secreting CD4 T cells, greater secretion of IL-4 and IL
      10, and lesser secretion of IFN-gamma after TCR stimulation with VIP. The level
      of VIP recognized by CD4 T cells thus is a major determinant of the relative
      contributions of Th subsets to the immune effector phenotype.

PMID- 12496415
TI  - Induction of the early growth response gene 1 promoter by TCR agonists and
      partial agonists: ligand potency is related to sustained phosphorylation of
      extracellular signal-related kinase substrates.
AB  - Responses to partial agonist TCR signals include positive selection of
      thymocytes, survival of naive T cells, and homeostatic proliferation. As part of
      an effort to understand the molecular basis of these processes, we have
      determined how agonist and partial agonist ligands act differently to induce a
      change in gene expression. We have found that the early growth response gene 1
      (Egr1) promoter is activated by agonist and partial agonist ligands, but the
      partial agonist induces 10-fold lower promoter activity. Both agonist and partial
      agonist ligands require all six serum response elements in the Egr1 promoter to
      reach maximum induction. Although slightly fewer cells respond to the partial
      agonist, all of the responding cells have reduced activity compared with the
      cells responding to agonist. The factors binding to the serum response elements
      of the Egr1 promoter form a ternary complex (TC) consisting of serum response
      factor and either Elk-1 or serum response factor accessory protein-1a. Formation
      of a stable TC and inducible promoter activity are both dependent on
      extracellular signal-related kinase activation. Examination of TC formation over
      time reveals that this complex is induced well by partial agonist ligands, but it
      is not sustained, whereas agonist stimulation induces longer lived TCs.
      Therefore, the data suggest that both agonist and partial agonist ligands can
      induce formation of multiple TC on the Egr1 promoter, but the ability of the
      agonist ligand to maintain these complexes for an extended time results in the
      increased potency of the agonist.

PMID- 12496416
TI  - Minimal requirement of tyrosine residues of linker for activation of T cells in
      TCR signaling and thymocyte development.
AB  - Linker for activation of T cells (LAT) is a membrane-associated adaptor protein
      that is phosphorylated on multiple tyrosines upon TCR cross-linking. Previous
      studies show that LAT is essential for TCR-mediated signaling and thymocyte
      development. In this study, we expressed a series of LAT Tyr to Phe mutants in
      LAT-deficient J.CaM2.5 cells and examined their tyrosine phosphorylation;
      association with Grb2, Gads, and phospholipase C (PLC)-gamma1; and function in T
      cell activation. Our results showed that the five membrane-distal tyrosines were
      phosphorylated upon T cell activation. Grb2, Gads, and PLC-gamma1 associated with
      LAT preferentially via different sets of tyrosine residues; however, they failed
      to interact with LAT mutants containing only one tyrosine. We also determined the
      minimal requirement of LAT tyrosine residues in T cell activation and thymocyte
      development. Our results showed that a minimum of three tyrosines is required for
      LAT to function in T cell activation and thymocyte development. LAT mutants that
      were capable of binding Grb2 and PLC-gamma1 could reconstitute T cell activation
      in LAT-deficient cells and thymocyte development in LAT-deficient mice.

PMID- 12496417
TI  - Regulation of cell type-specific mouse Fc epsilon RI beta-chain gene expression
      by GATA-1 via four GATA motifs in the promoter.
AB  - The FcR beta-chain, a subunit of two related multisubunit receptor complexes, the
      FcepsilonRI and FcgammaRIII, amplifies the mast cell response and is necessary
      for the cell surface expression of FcepsilonRI in mouse. The transient reporter
      assay indicated that -69/+4 region is required for cell type-specific
      transcriptional regulation of mouse beta-chain gene. EMSA using Abs against
      transcription factors or competitive oligonucleotides demonstrated that -58/-40
      region (containing overlapping three GATA-1 sites, -53/-48, -46/-51, and -42/-47)
      and -31/-26 region (containing one GATA-1 site) are recognized by GATA-1. The
      promoter activity of beta-chain was decreased by nucleotide replacements of the
      GATA-1 sites in mouse mast cell line PT18. Furthermore, exogenously produced GATA
      1 up-regulated the promoter activity in CV-1 cells, which are negative in the
      beta-chain production and the up-regulation was apparently suppressed by GATA-1
      site mutations. These results indicate that cell type-specific transcription of
      mouse beta-chain gene is regulated by GATA-1.

PMID- 12496418
TI  - Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced
      cell death.
AB  - TWEAK, a TNF family member, is produced by IFN-gamma-stimulated monocytes and
      induces multiple pathways of cell death, including caspase-dependent apoptosis,
      cathepsin B-dependent necrosis, and endogenous TNF-alpha-mediated cell death, in
      a cell type-specific manner. However, the TWEAK receptor(s) that mediates these
      multiple death pathways remains to be identified. Recently, fibroblast growth
      factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which was
      responsible for TWEAK-induced proliferation of endothelial cells and
      angiogenesis. Because Fn14 lacks the cytoplasmic death domain, it remains unclear
      whether Fn14 can also mediate the TWEAK-induced cell death. In this study, we
      demonstrated that TWEAK could induce apoptotic cell death in Fn14 transfectants.
      A pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, rather
      sensitized the Fn14 transfectants to TWEAK-induced cell death by necrosis via
      reactive oxygen intermediates and cathepsin B-dependent pathway. By using newly
      generated agonistic anti-Fn14 mAbs, we also observed that Fn14 is constitutively
      expressed on the cell surface of all TWEAK-sensitive tumor cell lines, and can
      transmit the multiple death signals. Moreover, an anti-Fn14 mAb that blocks TWEAK
      Fn14 interaction could totally abrogate TWEAK binding and TWEAK-induced cell
      death in all TWEAK-sensitive tumor cell lines. These results revealed that the
      multiple pathways of TWEAK-induced cell death are solely mediated by Fn14.

PMID- 12496420
TI  - Serial analysis of gene expression in circulating gamma delta T cell subsets
      defines distinct immunoregulatory phenotypes and unexpected gene expression
      profiles.
AB  - Gene expression profiles were compared in circulating bovine GD3.5+ (CD8-) and
      GD3.5- (predominantly CD8+) gammadelta T cells using serial analysis of gene
      expression (SAGE). Approximately 20,000 SAGE tags were generated from each
      library. A comparison of the two libraries demonstrated 297 and 173 tags
      representing genes with 5-fold differential expression in GD3.5+ and GD3.5-
      gammadelta T cells, respectively. Consistent with their localization into sites
      of inflammation, GD3.5+ gammadelta T cells appeared transcriptionally and
      translationally more active than GD3.5- gammadelta cells. GD3.5- gammadelta T
      cells demonstrated higher expression of the cell proliferation inhibitor BAP 37,
      which was associated with their less activated gene expression phenotype. The
      immune regulatory and apoptosis-inducing molecule, galectin-1, was identified as
      a highly abundant molecule and was higher in GD3.5+gammadelta T cells. Surface
      molecules attributed to myeloid cells, such as CD14, CD68, and scavenger receptor
      1, were identified in both populations. Furthermore, expression of B lymphocyte
      induced maturation protein, a master regulator of B cell and myeloid cell
      differentiation, was identified by SAGE analysis and was confirmed at the RNA
      level to be selectively expressed in gammadelta T cells vs alphabeta T cells.
      These results provide new insights into the inherent differences between
      circulating gammadelta T cell subsets.

PMID- 12496419
TI  - Expression of the Grb2-related protein of the lymphoid system in B cell subsets
      enhances B cell antigen receptor signaling through mitogen-activated protein
      kinase pathways.
AB  - Adapter proteins play a critical role in regulating signals triggered by Ag
      receptor cross-linking. These small molecules link receptor proximal events with
      downstream signaling pathways. In this study, we explore the expression and
      function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related
      adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in
      naive B cells and is down-regulated following B cell Ag receptor ligation. By
      contrast, germinal center and memory B cells express little or no GrpL. Using
      human B cell lines, we detected constitutive interactions between GrpL and B cell
      linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa,
      hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL
      binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2
      domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a
      GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular
      signal-related kinase and p38 mitogen-activated protein kinase phosphorylation.
      Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor
      mediated signaling events.

PMID- 12496421
TI  - Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and
      phospholipase C gamma 1 are required for NF-kappa B activation and lipid raft
      recruitment of protein kinase C theta induced by T cell costimulation.
AB  - The NF-kappaB activation pathway induced by T cell costimulation uses various
      molecules including Vav1 and protein kinase C (PKC)theta. Because Vav1 inducibly
      associates with further proteins including phospholipase C (PLC)gamma1 and Src
      homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76), we
      investigated their role for NF-kappaB activation in Jurkat leukemia T cell lines
      deficient for expression of these two proteins. Cells lacking SLP-76 or PLCgamma1
      failed to activate NF-kappaB in response to T cell costimulation. In contrast,
      replenishment of SLP-76 or PLCgamma1 expression restored CD3/CD28-induced IkappaB
      kinase (IKK) activity as well as NF-kappaB DNA binding and transactivation.
      PKCtheta activated NF-kappaB in SLP-76- and PLCgamma1-deficient cells, showing
      that PKCtheta is acting further downstream. In contrast, Vav1-induced NF-kappaB
      activation was normal in SLP-76(-) cells, but absent in PLCgamma1(-) cells.
      CD3/CD28-stimulated recruitment of PKCtheta and IKKgamma to lipid rafts was lost
      in SLP-76- or PLCgamma1-negative cells, while translocation of Vav1 remained
      unaffected. Accordingly, recruitment of PKCtheta to the immunological synapse
      strictly relied on the presence of SLP-76 and PLCgamma1, but synapse
      translocation of Vav1 identified in this study was independent from both
      proteins. These results show the importance of SLP-76 and PLCgamma1 for NF-kappaB
      activation and raft translocation of PKCtheta and IKKgamma.

PMID- 12496422
TI  - High affinity xenoreactive TCR:MHC interaction recruits CD8 in absence of binding
      to MHC.
AB  - The TCR from a xenoreactive murine cytotoxic T lymphocyte clone, AHIII 12.2,
      recognizes murine H-2D(b) complexed with peptide p1058 (FAPGFFPYL) as well as
      human HLA-A2.1 complexed with human self-peptide p1049 (ALWGFFPVL). To understand
      more about T cell biology and cross-reactivity, the ectodomains of the AHIII 12.2
      TCR have been produced in E. coli as inclusion bodies and the protein folded to
      its native conformation. Flow cytometric and surface plasmon resonance analyses
      indicate that human p1049/A2 has a significantly greater affinity for the murine
      AHIII 12.2 TCR than does murine p1058/D(b). Yet, T cell binding and cytolytic
      activity are independent of CD8 when stimulated with human p1049/A2 as
      demonstrated with anti-CD8 Abs that block CD8 association with MHC. Even in the
      absence of direct CD8 binding, stimulation of AHIII 12.2 T cells with "CD8
      independent" p1049/A2 produces p56(lck) activation and calcium flux. Confocal
      fluorescence microscopy and fluorescence resonance energy transfer flow cytometry
      demonstrate CD8 is recruited to the site of TCR:peptide MHC binding. Taken
      together, these results indicate that there exists another mechanism for
      recruitment of CD8 during high affinity TCR:peptide MHC engagement.

PMID- 12496423
TI  - The role of OX40 ligand interactions in the development of the Th2 response to
      the gastrointestinal nematode parasite Heligmosomoides polygyrus.
AB  - In these studies, we examined the effects of OX40 ligand (OX40L) deficiency on
      the development of Th2 cells during the Th2 immune response to the intestinal
      nematode parasite Heligmosomoides polygyrus. Elevations in IL-4 production and
      total and Ag-specific serum IgE levels were partially inhibited during both the
      primary and memory immune responses to H. polygyrus in OX40L(-/-) mice. The host
      protective memory response was compromised in OX40L(-/-) mice, as decreased worm
      expulsion and increased egg production were observed compared with H. polygyrus
      inoculated OX40L(+/+) mice. To further examine the nature of the IL-4 defect
      during priming, adoptively transferred DO11.10 T cells were analyzed in the
      context of the H. polygyrus response. Although Ag-specific T cell IL-4 production
      was reduced in the OX40L(-/-) mice following immunization with OVA peptide plus
      H. polygyrus, Ag-specific T cell expansion, cell cycle progression, CXCR5
      expression, and migration were comparable between OX40L(+/+) and OX40L(-/-) mice
      inoculated with OVA and H. polygyrus. These studies suggest an important role for
      OX40/OX40L interactions in specifically promoting IL-4 production, as well as
      associated IgE elevations, in Th2 responses to H. polygyrus. However, OX40L
      interactions were not required for serum IgG1 elevations, increases in germinal
      center formation, and Ag-specific Th2 cell expansion and migration to the B cell
      zone.

PMID- 12496424
TI  - CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and
      Th2 cells, Leishmania major infection, and colitis in mice.
AB  - Regulatory T cells play a major role in modulating the immune response. However,
      most information on these cells centers on autoimmunity, and there is also
      considerable controversy on the functional characteristics of these cells. Here
      we provide direct in vitro and in vivo evidence that CD4+CD25+ regulatory T cells
      inhibit the differentiation and functions of both Th1 and Th2 cells. Importantly,
      CD4+CD25+ T cells suppressed the disease development of Leishmania major
      infection in SCID mice reconstituted with naive CD4+CD25- T cells. Furthermore,
      CD4+CD25+ T cells inhibited the development of colitis induced by both Th1 and
      Th2 cells in SCID mice. Our results therefore document that CD4+CD25+ regulatory
      T cells suppress both Th1 and Th2 cells and that these regulatory T cells have a
      profound therapeutic potential against diseases induced by both Th1 and Th2 cells
      in vivo.

PMID- 12496425
TI  - Human CD4+ T cells present within the microenvironment of human lung tumors are
      mobilized by the local and sustained release of IL-12 to kill tumors in situ by
      indirect effects of IFN-gamma.
AB  - By implanting nondisrupted pieces of human lung tumor biopsy tissues into SCID
      mice, it has been possible to establish viable grafts of the tumor, as well as
      the tumor-associated microenvironment, including inflammatory cells, fibroblasts,
      tumor vasculature, and the extracellular matrix. Using this xenograft model, we
      have evaluated and characterized the effects of a local and sustained release of
      human rIL-12 (rhIL-12) from biodegradable microspheres. In response to rhIL-12,
      the human CD45+ inflammatory cells present within the xenograft mediate the
      suppression or the complete arrest of tumor growth in SCID mice. Analysis of the
      cellular events reveals that human CD4+ and CD8+ T cells are induced by rhIL-12
      to produce and secrete IFN-gamma. Serum levels of human IFN-gamma in mice bearing
      rhIL-12-treated tumor xenografts correlate directly with the degree of tumor
      suppression, while neutralizing Abs to human IFN-gamma abrogate the IL-12
      mediated tumor suppression. Gene expression profiling of tumors responding to
      intratumoral rhIL-12 demonstrates an up-regulation of IFN-gamma and IFN-gamma
      dependent genes not observed in control-treated tumors. Genes encoding a number
      of proinflammatory cytokines, chemokines (and their receptors), adhesion
      molecules, activation markers, and the inducible NO synthase are up-regulated
      following the introduction of rhIL-12, while genes associated with tumor growth,
      angiogenesis, and metastasis are decreased in expression. NO contributes to the
      tumor killing because an inhibitor of inducible NO synthase prevents IL-12
      induced tumor suppression. Cell depletion studies reveal that the IL-12-induced
      tumor suppression, IFN-gamma production, and the associated changes in gene
      expression are all dependent upon CD4+ T cells.

PMID- 12496426
TI  - Identification of mouse MD-2 residues important for forming the cell surface TLR4
      MD-2 complex recognized by anti-TLR4-MD-2 antibodies, and for conferring LPS and
      taxol responsiveness on mouse TLR4 by alanine-scanning mutagenesis.
AB  - The expression of MD-2, which associates with Toll-like receptor (TLR) 4 on the
      cell surface, confers LPS and LPS-mimetic Taxol responsiveness on TLR4. Alanine
      scanning mutagenesis was performed to identify the mouse MD-2 residues important
      for conferring LPS and Taxol responsiveness on mouse TLR4, and for forming the
      cell surface TLR4-MD-2 complex recognized by anti-TLR4-MD-2 Ab MTS510. Single
      alanine mutations were introduced into mouse MD-2 (residues 17-160), and the
      mutants were expressed in a human cell line expressing mouse TLR4. Mouse MD-2
      mutants, in which a single alanine mutation was introduced at Cys37, Leu71,
      Leu78, Cys95, Tyr102, Cys105, Glu111, Val113, Ile117, Pro118, Phe119, Glu136,
      Ile138, Leu146, Cys148, or Thr152, showed dramatically reduced ability to form
      the cell surface mouse TLR4-mouse MD-2 complex recognized by MTS510, and the
      mutants also showed reduced ability to confer LPS and Taxol responsiveness. In
      contrast, mouse MD-2 mutants, in which a single alanine mutation was introduced
      at Tyr34, Tyr36, Gly59, Val82, Ile85, Phe126, Pro127, Gly129, Ile153, Ile154, and
      His155 showed normal ability to form the cell surface mouse TLR4-mouse MD-2
      complex recognized by MTS510, but their ability to confer LPS and Taxol
      responsiveness was apparently reduced. These results suggest that the ability of
      MD-2 to form the cell surface mouse TLR4-mouse MD-2 complex recognized by MTS510
      is essential for conferring LPS and Taxol responsiveness on TLR4, but not
      sufficient. In addition, the required residues at codon numbers 34, 85, 101, 122,
      and 153 for the ability of mouse MD-2 to confer LPS responsiveness are partly
      different from those for Taxol responsiveness.

PMID- 12496427
TI  - Transgenic expression of stromal cell-derived factor-1/CXC chemokine ligand 12
      enhances myeloid progenitor cell survival/antiapoptosis in vitro in response to
      growth factor withdrawal and enhances myelopoiesis in vivo.
AB  - Hemopoiesis is regulated in part by survival/apoptosis of hemopoietic
      stem/progenitor cells. Exogenously added stromal cell-derived factor-1 ((SDF
      1)/CXC chemokine ligand (CXCL)12) enhances survival/antiapoptosis of myeloid
      progenitor cells in vitro. To further evaluate SDF-1/CXCL12 effects on progenitor
      cell survival, transgenic mice endogenously expressing SDF-1/CXCL12 under a Rous
      sarcoma virus promoter were produced. Myeloid progenitors (CFU-granulocyte
      macrophage, burst-forming unit-erythroid, CFU-granulocyte-erythrocyte
      megakaryocyte-monocyte) from transgenic mice were studied for in vitro survival
      in the context of delayed addition of growth factors. SDF-1-expressing transgenic
      myeloid progenitors were enhanced in survival and antiapoptosis compared with
      their wild-type littermate counterparts. Survival-enhancing effects were due to
      release of low levels of SDF-1/CXCL12 and mediated through CXCR4 and G(alpha)i
      proteins as determined by ELISA, an antagonist to CXCR4, Abs to CXCR4 and SDF-1,
      and pertussis toxin. Transgenic effects of low SDF-1/CXCR4 may be due to synergy
      of SDF-1/CXCL12 with other cytokines; low SDF-1/CXCL12 synergizes with low
      concentrations of other cytokines to enhance survival of normal mouse myeloid
      progenitors. Consistent with in vitro results, progenitors from SDF-1/CXCL12
      transgenic mice displayed enhanced marrow and splenic myelopoiesis: greatly
      increased progenitor cell cycling and significant increases in progenitor cell
      numbers. These results substantiate survival effects of SDF-1/CXCL12, now
      extended to progenitors engineered to endogenously produce low levels of this
      cytokine, and demonstrate activity in vivo for SDF-1/CXCL12 in addition to cell
      trafficking.

PMID- 12496428
TI  - Survival of Mycobacterium tuberculosis in host macrophages involves resistance to
      apoptosis dependent upon induction of antiapoptotic Bcl-2 family member Mcl-1.
AB  - Mcl-1 protein expression was found to be up-regulated during infection with
      virulent Mycobacterium tuberculosis strain H37Rv. Mcl-1 induction in THP-1 cells
      was optimal at a multiplicity of infection of 0.8-1.2 bacilli per macrophage and
      was independent of opsonin coating of the bacteria. Mcl-1 expression was elevated
      as early as 4 h, peaked at 5.8-fold above control cells at 24 h, and remained
      elevated at 48 h after infection. In THP-1 cells, mMcl-1 mRNA was induced by
      infection with live H37Rv but not with attenuated M. tuberculosis strain H37Ra,
      heat-killed H37Rv, or latex beads. In THP-1 cells and monocyte-derived
      macrophages (MDMs), Mcl-1 protein was induced by infection with live H37Rv but
      not with attenuated M. tuberculosis strain H37Ra, heat-killed H37Rv, or latex
      beads. Treatment of uninfected, H37Ra-infected, and H37Rv-infected THP-1 cells
      and MDMs with antisense oligonucleotides to mcl-1 reduced Mcl-1 expression by
      >84%. This resulted in an increase in apoptosis of both MDMs and THP-1 cells that
      were infected with H37Rv, but not cells that were uninfected or infected with
      H37Ra. Increased apoptosis correlated with a decrease in M. tuberculosis CFUs
      recovered from antisense-treated, H37Rv-infected cells at 4 and 7 days after
      infection. In contrast, CFU recoveries from sense-treated, H37Rv-infected cells
      or from antisense- or sense-treated, H37Ra-infected cells were unchanged from
      controls. Thus, the antiapoptotic effect of the induction of Mcl-1 expression in
      H37Rv-infected macrophages promotes the survival of virulent M. tuberculosis.

PMID- 12496429
TI  - Toll-like receptor 2 participates in mediation of immune response in experimental
      pneumococcal meningitis.
AB  - Heterologous expression of Toll-like receptor (TLR)2 and CD14 in Chinese hamster
      ovary fibroblasts was reported to confer responsiveness to pneumococcal
      peptidoglycan. The present study characterized the role of TLR2 in the host
      immune response and clinical course of pneumococcal meningitis. Pneumococcal
      infection of mice caused a significant increase in brain TLR2 mRNA expression at
      both 4 and 24 h postchallenge. Mice with a targeted disruption of the TLR2 gene
      (TLR2-/-) showed a moderate increase in disease severity, as evidenced by an
      aggravation of meningitis-induced intracranial complications, a more pronounced
      reduction in body weight and temperature, and a deterioration of motor
      impairment. These symptoms were associated with significantly higher cerebellar
      and blood bacterial titers. Brain expression of the complement inhibitor
      complement receptor-related protein y was significantly higher in infected TLR2-/
      than in wild-type mice, while the expression of the meningitis-relevant
      inflammatory mediators IL-1beta, TNF-alpha, IL-6, macrophage-inflammatory protein
      (MIP)-2, inducible NO synthase, and C3 was similar in both genotypes. We first
      ectopically expressed single candidate receptors in HEK293 cells and then applied
      peritoneal macrophages from mice lacking TLR2 and/or functional TLR4 for further
      analysis. Overexpression of TLR2 and TLR4/MD-2 conferred activation of NF-kappaB
      in response to pneumococcal exposure. However, pneumococci-induced TNF-alpha
      release from peritoneal macrophages of wild-type and TLR2/functional TLR4/double
      deficient mice did not differ. Thus, while TLR2 plays a significant role in vivo,
      yet undefined pattern recognition receptors contribute to the recognition of and
      initiation of the host immune defense toward Streptococcus pneumoniae infection.

PMID- 12496430
TI  - Proteomics and immunological analysis of a novel shrimp allergen, Pen m 2.
AB  - Shellfish are a common cause of adverse food reactions in hypersensitive
      individuals and shrimp is one of the most frequently reported causes of allergic
      reactions. A novel allergen from Penaeus monodon, designated Pen m 2, was
      identified by two-dimensional immunoblotting using sera from subjects with shrimp
      allergy, followed by matrix-assisted laser desorption ionization time-of-flight
      mass spectrometry analysis of the peptide digest. This novel allergen was then
      cloned and the amino acid sequence deduced from the cDNA sequence. The cloned
      cDNA encoded a 356-aa protein with an acetylated N terminus at Ala2, identified
      by postsource decay analysis. Comparison of the Pen m 2 sequence with known
      protein sequences revealed extensive similarity with arginine kinase (EC 2.7.3.3)
      from crustaceans. Pen m 2 was purified by anion exchange chromatography and shown
      to have arginine kinase activity and to react with serum IgE from shrimp allergic
      patients and induce immediate type skin reactions in sensitized patients. Using
      Pen m 2-specific antisera and polyclonal sera from shrimp-sensitive subjects in a
      competitive ELISA inhibition assay, Pen m 2 was identified as a novel cross
      reactive Crustacea allergen. This novel allergen could be useful in allergy
      diagnosis and in the treatment of Crustacea-derived allergic disorders.

PMID- 12496431
TI  - Chimeras of labile toxin one and cholera toxin retain mucosal adjuvanticity and
      direct Th cell subsets via their B subunit.
AB  - Native cholera toxin (nCT) and the heat-labile toxin 1 (nLT) of enterotoxigenic
      Escherichia coli are AB5-type enterotoxins. Both nCT and nLT are effective
      adjuvants that promote mucosal and systemic immunity to protein Ags given by
      either oral or nasal routes. Previous studies have shown that nCT as mucosal
      adjuvant requires IL-4 and induces CD4-positive (CD4+) Th2-type responses, while
      nLT up-regulates Th1 cell production of IFN-gamma and IL-4-independent Th2-type
      responses. To address the relative importance of the A or B subunits in CD4+ Th
      cell subset responses, chimeras of CT-A/LT-B and LT-A/CT-B were constructed. Mice
      nasally immunized with CT-A/LT-B or LT-A/CT-B and the weak immunogen OVA
      developed OVA-specific, plasma IgG Abs titers similar to those induced by either
      nCT or nLT. Both CT-A/LT-B and LT-A/CT-B promoted secretory IgA anti-OVA Ab,
      which established their retention of mucosal adjuvant activity. The CT-A/LT-B
      chimera, like nLT, induced OVA-specific mucosal and peripheral CD4+ T cells
      secreting IFN-gamma and IL-4-independent Th2-type responses, with plasma IgG2a
      anti-OVA Abs. Further, LT-A/CT-B, like nCT, promoted plasma IgG1 more than IgG2a
      and IgE Abs with OVA-specific CD4+ Th2 cells secreting high levels of IL-4, but
      not IFN-gamma. The LT-A/CT-B chimera and nCT, but not the CT-A/LT-B chimera or
      nLT, suppressed IL-12R expression and IFN-gamma production by activated T cells.
      Our results show that the B subunits of enterotoxin adjuvants regulate IL-12R
      expression and subsequent Th cell subset responses.

PMID- 12496432
TI  - Characterization of lung gamma delta T cells following intranasal infection with
      Mycobacterium bovis bacillus Calmette-Guerin.
AB  - The lungs are considered to have an impaired capacity to contain infection by
      pathogenic mycobacteria, even in the presence of effective systemic immunity. In
      an attempt to understand the underlying cellular mechanisms, we characterized the
      gammadelta T cell population following intranasal infection with Mycobacterium
      bovis bacillus Calmette-Guerin (BCG). The peak of gammadelta T cell expansion at
      7 days postinfection preceded the 30 day peak of alphabeta T cell expansion and
      bacterial count. The expanded population of gammadelta T cells in the lungs of
      BCG-infected mice represents an expansion of the resident Vgamma2 T cell subset
      as well as an influx of Vgamma1 and of four different Vdelta gene-bearing T cell
      subsets. The gammadelta T cells in the lungs of BCG-infected mice secreted IFN
      gamma following in vitro stimulation with ionomycin and PMA and were cytotoxic
      against BCG-infected peritoneal macrophages as well as against the uninfected
      J774 macrophage cell line. The cytotoxicity was selectively blocked by anti
      gammadelta TCR mAb and strontium ions, suggesting a granule-exocytosis killing
      pathway. Depletion of gammadelta T cells by injection of specific mAb had no
      effect on the subsequent developing CD4 T cell response in the lungs of BCG
      infected mice, but significantly reduced cytotoxic activity and IFN-gamma
      production by lung CD8 T cells. Thus, gammadelta T cells in the lungs might help
      to control mycobacterial infection in the period between innate and classical
      adaptive immunity and may also play an important regulatory role in the
      subsequent onset of alphabeta T lymphocytes.

PMID- 12496433
TI  - Lack of C3 affects Th2 response development and the sequelae of chemotherapy in
      schistosomiasis.
AB  - The role of the third component of complement (C3) during schistosome infection
      was investigated using mice deficient in C3. While no effect was observed 8 wk
      after infection on worm development or liver pathology, Ag-specific Th2
      associated cytokine production (IL-13, IL-5, IL-6, and IL-10) was significantly
      reduced, and IFN-gamma production was enhanced in the absence of C3. IgG1 and
      IgE, but not IgG2a or IgM, Ab responses were also significantly impaired in
      infected C3(-/-) mice, suggesting that C3 may play a role in IL-4-mediated Th2
      response enhancement during schistosome infection. Furthermore, C3-deficient mice
      could not effectively clear adult worms after praziquantel (PZQ) treatment and
      suffered increased morbidity due to the overproduction of proinflammatory
      mediators following drug administration. However, the ischemic liver damage that
      normally accompanies PZQ administration in infected wild-type mice was
      substantially reduced in treated C3-deficient mice, probably due to the absence
      of dead or dying worms in the livers of these animals. Together these results
      indicate that C3 enhances Th2 responses during schistosome infection, potentiates
      PZQ-mediated parasite clearance, and reduces chemotherapy-induced proinflammatory
      mediator production.

PMID- 12496434
TI  - Ablation of CD8 and CD4 T cell responses by high viral loads.
AB  - To evaluate the impact of sustained viral loads on anti-viral T cell responses we
      compared responses that cleared acute lymphocytic choriomeningitis virus
      infection with those that were elicited but could not resolve chronic infection.
      During acute infection, as replicating virus was cleared, CD8 T cell responses
      were down-regulated, and a pool of resting memory cells developed. In chronically
      infected hosts, the failure to control the infection was associated with
      pronounced and prolonged activation of virus-specific CD8 T cells. Nevertheless,
      there was a progressive diminution of their effector activities as their capacity
      to produce first IL-2, then TNF-alpha, and finally IFN-gamma was lost. Chronic
      lymphocytic choriomeningitis virus infection was also associated with
      differential contraction of certain CD8 T cell responses, resulting in altered
      immunodominance. However, this altered immunodominance was not due to selective
      expansion of T cells expressing particular TCR Vbeta segments during chronic
      infection. High viral loads were not only associated with the ablation of CD8 T
      cell responses, but also with impaired production of IL-2 by virus-specific CD4 T
      cells. Taken together, our data show that sustained exposure to high viral loads
      results in the progressive functional inactivation of virus-specific T cell
      responses, which may further promote virus persistence.

PMID- 12496435
TI  - Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum
      that mediates binding to CD18 receptors on human macrophages.
AB  - Histoplasma capsulatum (Hc), is a facultative intracellular fungus that binds to
      CD11/CD18 receptors on macrophages (Mphi). To identify the ligand(s) on Hc yeasts
      that is recognized by Mphi, purified human complement receptor type 3 (CR3,
      CD11b/CD18) was used to probe a Far Western blot of a detergent extract of Hc
      cell wall and cell membrane. CR3 recognized a single 60-kDa protein, which was
      identified as heat shock protein 60 (hsp60). Biotinylation of viable yeasts,
      followed by precipitation with streptavidin-coated beads, and Western blotting
      with anti-hsp60 demonstrated that hsp60 was on the surface of Hc yeasts. Electron
      and confocal microscopy revealed that hsp60 resided on the yeast cell wall in
      discrete clusters. Recombinant hsp60 (rhsp60) inhibited attachment of Hc yeasts
      to Mphi. Recombinant hsp60 and Abs to CD11b and CD18 inhibited binding of yeasts
      to Chinese hamster ovary cells transfected with CR3 (CHO3). Polystyrene beads
      coated with rhsp60 bound to Mphi, and attachment was inhibited by Abs to CD11 and
      CD18. Freeze/thaw extract (F/TE), a preparation of Hc yeast surface proteins that
      contained hsp60, inhibited the attachment of Hc yeasts to Mphi. Depletion of
      hsp60 from F/TE removed the capacity of F/TE to block binding of Hc to Mphi.
      Interestingly, rhsp60 did not inhibit binding of Hc yeasts to dendritic cells
      (DC), which recognize Hc via very late Ag 5. Moreover, F/TE inhibited attachment
      of Hc to DC even when depleted of hsp60. Thus, Hc hsp60 appears to be a major
      ligand that mediates attachment of Hc to Mphi CD11/CD18, whereas DC recognize Hc
      via a different ligand(s).

PMID- 12496436
TI  - HIV mucosal vaccine: nasal immunization with gp160-encapsulated hemagglutinating
      virus of Japan-liposome induces antigen-specific CTLs and neutralizing antibody
      responses.
AB  - Nasal immunization of normal mice with HIVgp160-encapsulated hemagglutinating
      virus of Japan (HVJ)-liposome induced high titers of gp160-specific neutralizing
      IgG in serum and IgA in nasal wash, saliva, fecal extract, and vaginal wash,
      along with both Th1- and Th2-type responses. HIVgp160-specific IgG- and IgA
      producing cells were also detected in mononuclear cells isolated from spleen,
      nasal cavity, salivary gland, intestinal lamina propria, and vaginal tissue of
      nasally immunized mice. In addition, CD8(+) CTLs were induced in mice nasally
      immunized with gp160-HVJ-liposome. These findings suggest that two layers of
      effective HIV-specific humoral and cellular immunity, in mucosal and systemic
      sites, were induced by this nasal vaccine. In immunodeficient mice, nasal
      immunization with gp160-HVJ-liposome induced Ag-specific immune responses for the
      systemic and mucosal compartments of both Th1 (IFN-gamma(-/-)) and Th2 (IL-4(-/
      )). In vitro Ag-specific serum IgG Ab and vaginal wash samples possessing IgA and
      IgG Abs that had been induced by nasal immunization with gp160-HVJ-liposome were
      able to neutralize a clinically isolated strain of HIV-MN strain isolated from
      Japanese hemophiliac patients. Taken together, these results suggest that, for
      the prevention and control of AIDS, nasally administered gp160-HVJ-liposome is a
      powerful immunization tool that induces necessary Ag-specific immune responses at
      different stages of HIV infection.

PMID- 12496437
TI  - Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor
      expression.
AB  - IL-6 is known to be an important pro- and anti-inflammatory cytokine, which is up
      regulated during sepsis. Our previous work has suggested a role for IL-6 in the
      up-regulation of C5aR in sepsis. We reported earlier that interception of C5a or
      C5aR results in improved outcomes in experimental sepsis. Using the cecal
      ligation/puncture (CLP) model in mice, we now demonstrate that treatment with
      anti-IL-6 Ab (anti-IL-6) results in significantly improved survival, dependent on
      the amount of Ab infused. CLP animals showed significantly increased binding of
      125I-labeled anti-C5aR to organs when compared to either control mice at 0 h or
      CLP animals infused with normal rabbit 125I-labeled IgG. Binding of 125I-labeled
      anti-C5aR to lung, liver, kidney, and heart was significantly decreased in anti
      IL-6-treated animals 6 h after CLP. RT-PCR experiments with mRNA isolated from
      various organs obtained 3, 6, and 12 h after CLP demonstrated increased C5aR mRNA
      expression during the onset of sepsis, which was greatly suppressed in CLP mice
      treated with anti-IL-6. These data suggest that IL-6 plays an important role in
      the increased expression of C5aR in lung, liver, kidney, and heart during the
      development of sepsis in mice and that interception of IL-6 leads to reduced
      expression of C5aR and improved survival.

PMID- 12496438
TI  - Induction of in vitro reprogramming by Toll-like receptor (TLR)2 and TLR4
      agonists in murine macrophages: effects of TLR "homotolerance" versus
      "heterotolerance" on NF-kappa B signaling pathway components.
AB  - In this study, tolerance induction by preexposure of murine macrophages to Toll
      like receptor (TLR)2 and TLR4 agonists was revisited, focusing on the major
      signaling components associated with NF-kappaB activation. Pretreatment of
      macrophages with a pure TLR4 agonist (protein-free Escherichia coli (Ec) LPS) or
      with TLR2 agonists (Porphyromonas gingivalis LPS or synthetic lipoprotein
      Pam3Cys) led to suppression of TNF-alpha secretion, IL-1R-associated kinase-1,
      and IkappaB kinase (IKK) kinase activities, c-jun N-terminal kinase, and
      extracellular signal-regulated kinase phosphorylation, and to suppression of NF
      kappaB DNA binding and transactivation upon challenge with the same agonist (TLR4
      or TLR2 "homotolerance," respectively). Despite inhibited NF-kappaB DNA binding,
      increased levels of nuclear NF-kappaB were detected in agonist-pretreated
      macrophages. For all the intermediate signaling elements, heterotolerance was
      weaker than TLR4 or TLR2 homotolerance with the exception of IKK kinase activity.
      IKK kinase activity was unperturbed in heterotolerance. TNF-alpha secretion was
      also suppressed in P. gingivalis LPS-pretreated, Ec LPS-challenged cells, but not
      vice versa, while Pam3Cys and Ec LPS did not induce a state of cross-tolerance at
      the level of TNF-alpha. Experiments designed to elucidate novel mechanisms of NF
      kappaB inhibition in tolerized cells revealed the potential contribution of
      IkappaBepsilon and IkappaBxi inhibitory proteins and the necessity of TLR4
      engagement for induction of tolerance to Toll receptor-IL-1R domain-containing
      adapter protein/MyD88-adapter-like-dependent gene expression. Collectively, these
      data demonstrate that induction of homotolerance affects a broader spectrum of
      signaling components than in heterotolerance, with selective modulation of
      specific elements within the NF-kappaB signaling pathway.

PMID- 12496439
TI  - Critical role of the alpha 4 integrin/VCAM-1 pathway in cerebral leukocyte
      trafficking in lupus-prone MRL/fas(lpr) mice.
AB  - MRL/fas(lpr) mice are affected by a systemic autoimmune disease that results in
      leukocyte recruitment to a wide range of vascular beds, including the cerebral
      microvasculature. The mechanisms responsible for the leukocyte trafficking to the
      brain in these animals are not known. Therefore, the aim of this study was to
      directly examine the cerebral microvasculature in MRL/fas(lpr) mice and determine
      the molecular mechanisms responsible for this leukocyte recruitment. Intravital
      microscopy was used to assess leukocyte-endothelial cell interactions (rolling,
      adhesion) in the pial microcirculation of MRL(+/+) (control) and MRL/fas(lpr)
      mice at 8, 12, and 16 wk of age. Leukocyte rolling and adhesion were rarely
      observed in MRL(+/+) mice of any age. MRL/fas(lpr) mice displayed similar results
      at 8 and 12 wk. However, at 16 wk, significant increases in leukocyte rolling and
      adhesion were observed in these mice. Histological analysis revealed that the
      interacting cells were exclusively mononuclear. Leukocyte rolling was reduced,
      but not eliminated in P-selectin(-/-)-MRL/fas(lpr) mice. However, leukocyte
      adhesion was not reduced in these mice, indicating that P-selectin-dependent
      rolling was not required for leukocyte recruitment to the cerebral vasculature in
      this model of systemic inflammation. E-selectin blockade also had no effect on
      leukocyte rolling. In contrast, blockade of either the alpha4 integrin or VCAM-1
      eliminated P-selectin-independent leukocyte rolling. alpha4 Integrin blockade
      also significantly inhibited leukocyte adhesion. These studies demonstrate that
      the systemic inflammatory response that affects MRL/fas(lpr) mice results in
      leukocyte rolling and adhesion in the cerebral microcirculation, and that the
      alpha4 integrin/VCAM-1 pathway plays a central role in mediating these
      interactions.

PMID- 12496440
TI  - House dust mite Dermatophagoides farinae augments proinflammatory mediator
      productions and accessory function of alveolar macrophages: implications for
      allergic sensitization and inflammation.
AB  - In this study, we examine the effects of Dermatophagoides farinae (Der f), a
      major source of airborne allergens, on alveolar macrophages (AMs), and we also
      test its contribution to allergic responses in mice. Der f activated NF-kappaB of
      AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In
      addition, it down-regulated antioxidants, but affected neither the expression nor
      production of IL-12. Der f-stimulated AMs expressed enhanced levels of
      costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell
      development. The enhanced accessory function was suppressed by blockade mAbs to
      B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase
      inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by
      (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and
      neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6
      and TNF-alpha productions and enhanced accessory function of AMs. Der f was more
      potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum
      allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice
      expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In
      Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3
      days before Der f instillation) augmented Der f-specific Ab production, whereas
      dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic
      airway inflammation and Ab response. We conclude that AMs are sensitive targets
      for Der f and that the Der f-induced proinflammatory responses may represent an
      important mechanism in mediating the development of allergic sensitization and
      inflammation.

PMID- 12496441
TI  - The CCR3 receptor is involved in eosinophil differentiation and is up-regulated
      by Th2 cytokines in CD34+ progenitor cells.
AB  - The involvement of chemokines in eosinophil recruitment during inflammation and
      allergic reactions is well established. However, a functional role for chemokines
      in eosinophil differentiation has not been investigated. Using in situ RT-PCR,
      immunostaining, and flow cytometric analysis, we report that human CD34+ cord
      blood progenitor cells contain CCR3 mRNA and protein. Activation of CD34+
      progenitor cells under conditions that promote Th2 type differentiation up
      regulated surface expression of the CCR3. In contrast, activation with IL-12 and
      IFN-gamma resulted in a significant decrease in the expression of CCR3. Eotaxin
      induced Ca2+ mobilization in CD34+ progenitor cells, which could explain the in
      vitro and in vivo chemotactic responsiveness to eotaxin. We also found that
      eotaxin induced the differentiation of eosinophils from cord blood CD34+
      progenitor cells. The largest number of mature eosinophils was found in cultures
      containing eotaxin and IL-5. The addition of neutralizing anti-IL-3, anti-IL-5,
      and anti-GM-CSF Abs to culture medium demonstrated that the differentiation of
      eosinophils in the presence of eotaxin was IL-3-, IL-5-, and GM-CSF-independent.
      These results could explain how CD34+ progenitor cells accumulate and persist in
      the airways and peripheral blood of patients with asthma and highlight an
      alternative mechanism by which blood and tissue eosinophilia might occur in the
      absence of IL-5.

PMID- 12496442
TI  - Oncostatin M regulates eotaxin expression in fibroblasts and eosinophilic
      inflammation in C57BL/6 mice.
AB  - Oncostatin M (OSM) is a member of the IL-6/LIF (or gp130) cytokine family, and
      its potential role in inflammation is supported by a number of activities
      identified in vitro. In this study, we investigate the action of murine OSM on
      expression of the CC chemokine eotaxin by fibroblasts in vitro and on mouse lung
      tissue in vivo. Recombinant murine OSM stimulated eotaxin protein production and
      mRNA levels in the NIH 3T3 fibroblast cell line. IL-6 could regulate a small
      induction of eotaxin in NIH 3T3 cells, but other IL-6/LIF cytokines (LIF,
      cardiotrophin-1 (CT-1)) had no effect. Cell signaling studies showed that murine
      OSM, LIF, IL-6, and CT-1 stimulated the tyrosine phosphorylation of STAT-3,
      suggesting STAT-3 activation is not sufficient for eotaxin induction in NIH 3T3
      cells. OSM induced ERK-1,2 and p38 mitogen-activated protein kinase
      phosphorylation in NIH 3T3 cells, and inhibitors of ERK (PD98059) or p38
      (SB203580) could partially reduce OSM-induced eotaxin production, suggesting
      partial dependence on mitogen-activated protein kinase signaling. OSM (but not
      LIF, IL-6, or CT-1) also induced eotaxin release by mouse lung fibroblast
      cultures derived from C57BL/6 mice. Overexpression of murine OSM in lungs of
      C57BL/6 mice using an adenovirus vector encoding murine OSM resulted in a
      vigorous inflammatory response by day 7 after intranasal administration,
      including marked extracellular matrix accumulation and eosinophil infiltration.
      Elevated levels of eotaxin mRNA in whole lung were detected at days 4 and 5.
      These data strongly support a role of OSM in lung inflammatory responses that
      involve eosinophil infiltration.

PMID- 12496443
TI  - Oxidant-mediated mitochondrial injury in eosinophil apoptosis: enhancement by
      glucocorticoids and inhibition by granulocyte-macrophage colony-stimulating
      factor.
AB  - The mainstay of asthma therapy, glucocorticosteroids (GCs) have among their
      therapeutic effects the inhibition of inflammatory cytokine production and
      induction of eosinophil apoptosis. In the absence of prosurvival cytokines (e.g.,
      GM-CSF), eosinophils appear to be short-lived, undergoing apoptosis over 96 h in
      vitro. In a dose-dependent manner, GC further enhances apoptosis, while
      prosurvival cytokines inhibit apoptosis and antagonize the effect of GC. The
      mechanisms of eosinophil apoptosis, its enhancement by GC, and antagonism of GC
      by GM-CSF are not well-understood. As demonstrated in this study, baseline
      apoptosis of eosinophils resulted from oxidant-mediated mitochondrial injury that
      was significantly enhanced by GC. Mitochondrial injury was detected by early and
      progressive loss of mitochondrial membrane potential and the antioxidant protein,
      Mn superoxide dismutase (SOD). Also observed was the activation/translocation of
      the proapoptotic protein, Bax, to mitochondria. Underscoring the role of oxidants
      was the inhibition of mitochondrial changes and apoptosis with culture in
      hypoxia, or pretreatment with a flavoprotein inhibitor or a SOD mimic. GCs
      demonstrated early (40 min) and late (16 h) activation of proapoptotic c-Jun NH2
      terminal kinase (JNK) and decreased the antiapoptotic protein X-linked inhibitor
      of apoptosis, a recently demonstrated inhibitor of JNK activation. Similarly,
      inhibition of JNK prevented GC-enhanced mitochondrial injury and apoptosis.
      Importantly, GM-CSF prevented GC-induced loss of X-linked inhibitor of apoptosis
      protein, late activation of JNK, and mitochondrial injury even in the face of
      unchanged oxidant production, loss of MnSOD, and early JNK activation. These data
      demonstrate that oxidant-induced mitochondrial injury is pivotal in eosinophil
      apoptosis, and is enhanced by GC-induced prolonged JNK activation that is in turn
      inhibited by GM-CSF.

PMID- 12496444
TI  - Repression of bleomycin-induced pneumopathy by TNF.
AB  - Idiopathic pulmonary fibrosis is a chronic inflammatory lung disease with
      interstitial fibrosis. As a potent proinflammatory cytokine, TNF has been
      suggested to play critical roles in the pathogenesis of the human disease and its
      animal model, bleomycin-induced pneumopathy. However, studies using TNF-deficient
      mice have demonstrated that TNF also has an anti-inflammatory function. To
      determine the role of TNF in pulmonary inflammation induced by bleomycin, we
      injected bleomycin intratracheally into TNF-deficient mice. In this study, we
      demonstrated persistent and intense inflammation in TNF-deficient mice due to
      reduced apoptosis of inflammatory cells. We also showed that in TNF-deficient
      mice, challenge via airways with murine, but not human rTNF, efficiently
      eliminated inflammatory cells from the bronchoalveolar space by apoptosis, and
      thus promoted tissue repair of damaged lungs. Contrary to previous reports that
      showed that TNF was a central mediator of pulmonary inflammation, we have
      demonstrated that TNF is essential for repressing pulmonary inflammation in
      bleomycin-induced pneumopathy.

PMID- 12496445
TI  - By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal
      antimicrobial response to lipopolysaccharide.
AB  - Epithelia react to microbial pathogens by mounting a defensive response that
      includes the production of antimicrobial peptides. In this study, we show that,
      in human epidermal cultures, Escherichia coli LPS was a very weak direct inducer
      of human beta-defensin (HBD)-2 mRNA and peptide, but the induction was greatly
      amplified when monocyte-derived cells (MoDeC) acted as intermediaries between LPS
      and the epidermis. IL-1R antagonist largely reversed the effect of MoDeC on
      epidermal HBD-2, indicating that, from among the many products of MoDeC, IL-1 was
      the dominant inducer of HBD-2 synthesis. In normal fresh human skin, which
      contains Langerhans cells and other myeloid cell types, in addition to
      keratinocytes, LPS also induced HBD-2 in an IL-1-dependent manner. In DNA
      microarray expression studies, HBD-2 was one of the most abundant mRNAs induced
      in epidermis by LPS-treated MoDeC, and its induction was reversed by IL-1Ra.
      Thus, epidermal response to LPS is potently amplified by MoDeC through IL-1
      mediated signaling, leading to a selective increase in the synthesis of the
      antimicrobial peptide HBD-2. This pattern of responses establishes a key role for
      both IL-1 and HBD-2 in the host defense reaction of the epidermis.

PMID- 12496446
TI  - CCR8 is not essential for the development of inflammation in a mouse model of
      allergic airway disease.
AB  - Chemokine receptors play an important role in the trafficking of various immune
      cell types to sites of inflammation. Several chemokine receptors are
      differentially expressed in Th1 and Th2 effector populations. Th2 cells
      selectively express CCR3, CCR4, and CCR8, which could direct their trafficking to
      sites of allergic inflammation. Additionally, increased expression of the CCR8
      ligand, TCA-3, has been detected in affected lungs in a mouse model of asthma. In
      this study, CCR8-deficient mice were generated to address the biological role of
      CCR8 in a model of allergic airway disease. Using two different protocols of
      allergen challenge, we demonstrate that absence of CCR8 does not affect the
      development of pulmonary eosinophilia and Th2 cytokine responses. In addition,
      administration of anti-TCA-3-neutralizing Ab during allergen sensitization and
      rechallenge failed to inhibit airway allergic inflammation. These results suggest
      that CCR8 does not play an essential role in the pathogenesis of inflammation in
      this mouse model of allergic airway disease.

PMID- 12496447
TI  - Antagonist of secondary lymphoid-tissue chemokine (CCR ligand 21) prevents the
      development of chronic graft-versus-host disease in mice.
AB  - The use of receptor antagonists for chemokines is an alternative approach to
      blocking chemokine actions and has the potential to provide novel therapeutics.
      We determined the receptor antagonist properties of murine N-terminally truncated
      secondary lymphoid tissue chemokine (SLC)/6Ckine/CCR ligand 21 analogs and
      evaluated the preventive effects of SLC antagonists on chronic graft-vs-host
      disease (GVHD) in a murine model by blocking the homing of donor CCR7-expressing
      T cells into the recipient's lymphoid organs. SLC analogs truncated >4 aa
      residues from the N terminus showed a loss of chemotaxis and Ca2+ influx of CCR7
      expressing cells and also inhibited SLC-stimulated chemotaxis and SLC-induced
      Ca2+ influx completely. To determine whether SLC antagonist inhibits the
      development of chronic GVHD, chronic GVHD was induced by injecting DBA/2 spleen
      cells into (C57BL/6 x DBA/2) F1 mice. Total numbers of spleen cells and host B
      cells, serum levels of IgE, and of total IgG and IgG1 of anti-DNA Abs in SLC
      antagonist-treated GVHD mice were significantly lower than those in control PBS
      treated GVHD mice. This was due to a reduction in the levels of activated donor
      CD4+ T cells and a decrease in IL-4 production, resulting in a reduction in the
      numbers of activated host B cells. Therefore, our results suggest that SLC
      antagonist has beneficial effects for the prevention of chronic GVHD.

PMID- 12496448
TI  - Impaired accumulation and function of memory CD4 T cells in human IL-12 receptor
      beta 1 deficiency.
AB  - Defects in IL-12 production or IL-12 responsiveness result in a vulnerability to
      infection with non-viral intracellular organisms, but the immunological
      mechanisms responsible for this susceptibility remain poorly understood. We
      present an immunological analysis of a patient with disseminated Salmonella
      enteritidis and a homozygous splice acceptor mutation in the IL-12Rbeta1-chain
      gene. This mutation resulted in the absence of IL-12Rbeta1 protein on PBMC and an
      inability of T cells to specifically bind IL-12 or produce IFN-gamma in response
      to either IL-12 or IL-23. The accumulation of memory (CD45R0(high)) CD4 T cells
      that were CCR7(high) (putative central memory cells) was normal or increased for
      age. Central memory CD4 T cells of the patient and age-matched controls were
      similar in having a low to undetectable capacity to produce IFN-gamma after
      polyclonal stimulation. In contrast, the patient had a substantial decrease in
      the number of CCR7(neg/dull) CD45R0(high) memory CD4 T cells (putative effector
      memory cells), and these differed from control cells in having a minimal ability
      to produce IFN-gamma after polyclonal stimulation. Importantly, tetanus toxoid
      specific IFN-gamma production by PBMC from the patient was also significantly
      reduced compared with that in age-matched controls, indicating that signaling via
      the IL-12Rbeta1-chain is generally necessary for the in vivo accumulation of
      human memory CD4 T cells with Th1 function. These results are also consistent
      with a model in which the IL-12Rbeta1 subunit is necessary for the conversion of
      central memory CD4 T cells into effector memory cells.

PMID- 12496450
TI  - IL-4-producing CD8+ T cells with a CD62L++(bright) phenotype accumulate in a
      subgroup of older adults and are associated with the maintenance of intact
      humoral immunity in old age.
AB  - An increased production of proinflammatory cytokines occurs in a high percentage
      of elderly persons and is associated with an impaired humoral immune response.
      However, high IL-4 production has also been observed in old age. We now
      demonstrate an IL-4-producing subpopulation of CD8+ T cells in a subgroup of
      healthy older adults. This T cell subset is substantial in size and has a
      characteristic phenotype expressing CD45RO, CD28, CD62L, and CD25. IL-4-producing
      CD8+ T cells produce large amounts of IL-2 but not IFN-gamma or perforin, and
      these cells do not have a regulatory suppressive effect on other T cells. In vivo
      IL-4-producing CD8+ T cells can be stably detected over a year. When put into
      culture they also have a stable cytokine production pattern but fail to produce
      perforin even in the presence of IL-12. This special T cell type does not occur
      in persons under the age of 40, but is present in 36% of the persons >60 years of
      age. In this age group, IL-4-producing CD8+ T cells are more frequent in persons
      who are still capable of raising a humoral immune response following immunization
      than in others who fail to produce protective Abs after vaccination. Our results
      suggest that CD8+ T cells with a CD62L++(bright) phenotype accumulate in a
      subgroup of older adults. Due to their phenotype that enables them to migrate
      into lymphoid tissues and to their capacity to produce IL-4, these cells may
      counterbalance the overproduction of proinflammatory cytokines in old age.

PMID- 12496449
TI  - Absence of IL-4 facilitates the development of chronic autoimmune myasthenia
      gravis in C57BL/6 mice.
AB  - Myasthenia gravis (MG) is a T cell-dependent, Ab-mediated autoimmune disease. Ab
      against muscle acetylcholine receptor (AChR) cause the muscular weakness that
      characterizes MG and its animal model, experimental MG (EMG). EMG is induced in
      C57BL6 (B6) mice by three injections of Torpedo AChR (TAChR) in adjuvant. B6 mice
      develop anti-TAChR Ab that cross-react with mouse muscle AChR, but their CD4+ T
      cells do not cross-react with mouse AChR sequences. Moreover, murine EMG is not
      self-maintaining as is human MG, and it has limited duration. Several studies
      suggest that IL-4 has a protecting function in EMG. Here we show that B6 mice
      genetically deficient in IL-4 (IL-4-/-) develop long-lasting muscle weakness
      after a single immunization with TAChR. They develop chronic self-reactive Ab,
      and their CD4+ T cells respond not only to the TAChR and TAChR subunit peptides,
      but also to several mouse AChR subunit peptides. These results suggest that in B6
      mice, regulatory mechanisms that involve IL-4 contribute to preventing the
      development of a chronic Ab-mediated autoimmune response to the AChR.

PMID- 12496451
TI  - Impaired processing and presentation by MHC class II proteins in human diabetic
      cells.
AB  - The biochemical processing of and Ag presentation by MHC class II molecules were
      examined in B cell lines derived from pairs of identical twins discordant for
      type 1 diabetes. MHC class II defects detected exclusively in cells derived from
      the twins with autoimmunity included increased rates of transport to and
      subsequent turnover at the cell surface, inadequate glycosylation, and a reduced
      display at the cell surface of antigenic peptides. These defects appeared to be
      secondary to a decreased abundance of the p35 isoform of the invariant chain
      (Ii), a human-specific chaperone protein for MHC class II normally generated by
      use of an alternative translation start site. Stable transfection of diabetic B
      cell lines with an Ii p35 expression vector corrected the defects in MHC class II
      processing and peptide presentation. A defect in the expression of Ii p35 may
      thus result in impairment of Ag presentation by MHC class II molecules and
      thereby contribute to the development of type 1 diabetes in at-risk genotypes.

PMID- 12496452
TI  - Autoimmune encephalomyelitis and uveitis induced by T cell immunity to self beta
      synuclein.
AB  - Beta-synuclein is a neuronal protein that accumulates in the plaques that
      characterize neurodegenerative diseases such as Parkinson's and Alzheimer's
      diseases. It has been proposed that immunization to peptides of plaque-forming
      proteins might be used therapeutically to help dissociate pathogenic plaques in
      the brain. We now report that immunization of Lewis rats with a peptide from beta
      synuclein resulted in acute paralytic encephalomyelitis and uveitis. T cell lines
      and clones reactive to the peptide adoptively transferred the disease to naive
      rats. Immunoblotting revealed the presence of beta-synuclein in heavy myelin,
      indicating that the expression of beta-synuclein is not confined to neurons.
      These results add beta-synuclein to the roster of encephalitogenic self Ags,
      point out the potential danger of therapeutic autoimmunization to beta-synuclein,
      and alert us to the unsuspected possibility that autoimmunity to beta-synuclein
      might play an inflammatory role in the pathogenesis of neurodegeneration.

PMID- 12496454
TI  - A lamellar model for the X-ray rocking curves of sagittally bent Laue crystals.
AB  - The use of sagittally bent asymmetric Laue crystals in horizontally focusing
      monochromators for high-energy synchrotron X-rays necessitates simulation of the
      X-ray reflectivity by such crystals. Based on the theory of the lattice
      distortion in the diffraction plane of sagittally bent Laue crystals, a lamellar
      model was developed to predict their rocking curves. The model was experimentally
      verified by rocking-curve measurements from various reflections on silicon
      crystals of four representative orientations, sagittally bent to various radii,
      using X-rays of 67 keV energy.

PMID- 12496453
TI  - Dichotomy of autoreactive Th1 and Th2 cell responses to desmoglein 3 in patients
      with pemphigus vulgaris (PV) and healthy carriers of PV-associated HLA class II
      alleles.
AB  - Pemphigus vulgaris (PV) is the most severe autoimmune bullous skin disorder and
      is primarily associated with circulating autoantibodies (autoAb) against
      desmoglein 3 (Dsg3). In light of recent evidence that autoreactive T cells are
      critical for the induction and regulation of Ab production, the goal of this
      study was to characterize and quantitate autoreactive T cells in patients with PV
      and healthy controls. Peripheral Dsg3-reactive Th cells from 28 patients with
      acute-onset, chronic active, and remittent PV were quantitated by MACS secretion
      assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all
      studied PV patients, while the number of autoreactive Th1 cells exceeded those of
      Th2 cells in chronic active PV. In contrast, healthy carriers of the PV
      associated HLA class II alleles, DRB1*0402 and DQB1*0503, exhibited exclusively
      Dsg3-reactive Th1 cell responses, while healthy carriers of other HLA class II
      alleles did not. Moreover, the presence of IgG1 and IgG4 against Dsg3 was
      directly related to the ratio of Dsg3-reactive Th1/Th2 cells. T cell recognition
      of Dsg3 was restricted by HLA-DRB1*0402 and DQB1*0503 in PV patients and Dsg3
      responsive healthy donors. These observations strongly suggest 1) that the
      appearance of Dsg3-reactive Th2 cells is restricted to patients with PV; 2) that
      specific HLA class II alleles that are prevalent in PV are critical for T cell
      recognition of Dsg3 in PV patients and Dsg3-responsive healthy donors; and 3)
      that autoAb production is associated with both Th1 and Th2 cells.

PMID- 12496455
TI  - Extension of the time-dependent dynamical diffraction theory to 'optical phonon'
      type distortions: application to diffraction from coherent acoustic and optical
      phonons.
AB  - An extension of the time-dependent Takagi-Taupin theory to 'optical phonon'-type
      distortions is presented. By splitting the susceptibility into the contributions
      from each atom in a unit cell, modifications to the structure factor as well as
      lattice parameter are taken into account. The result is a compact, surprisingly
      simple, equation with a strong formal similarity to the classical Takagi-Taupin
      equation, with the latter included as a special case. Time dependence is
      explicitly retained and thus the analysis is applicable to situations where the
      crystal is modified on time scales comparable with that for the X-rays to
      traverse an extinction depth. A comparison is made between the influence of
      coherent acoustic and optical phonons on the diffraction of X-rays. Numerical and
      perturbative analytical solutions of the generalized Takagi-Taupin equation are
      presented in the presence of such phonons.

PMID- 12496456
TI  - On the enumeration of the simple 3-polyhedra.
AB  - It will be proved that the simple 3-polyhedra with f + 1 facets are obtained from
      all simple 3-polyhedra with f facets by 2-face splits. The numbers of
      combinatorial types of simple 3-polyhedra with up to 15 facets are stated with
      respect to their automorphism group order.

PMID- 12496457
TI  - Structure and stability of alpha- and beta-Ti2Se. Electron diffraction versus
      density-functional theory calculations.
AB  - The alpha structure as well as the new beta modification of Ti(2)Se were recently
      characterized by electron diffraction structural analysis of nanosize
      crystallites. In this study, both structures are investigated by means of total
      energy calculations within the non-local density-functional theory in order to
      validate the experimental results. The calculated parameters for both
      modifications are in excellent agreement with data determined from electron
      microscopy. From the calculated equation of states, beta-Ti(2)Se is predicted to
      be a high-pressure modification. The present investigation proves by a well
      established non-crystallographic method that unknown structures, which are not
      accessible by other standard crystallographic techniques, can be solved and
      refined with high accuracy using electron diffraction data.

PMID- 12496458
TI  - Three-periodic nets and tilings: regular and quasiregular nets.
AB  - Regular nets are defined as those with symmetry that requires the coordination
      figure to be a regular polygon or polyhedron. It is shown that this definition
      leads to five regular 3-periodic nets. There is also one quasiregular net with a
      quasiregular coordination figure. The natural tiling of a net and its associated
      essential rings are also defined, and it is shown that the natural tilings of the
      regular nets have the property that there is just one kind of vertex, one kind of
      edge, one kind of ring and one kind of tile, i.e. transitivity 1111. The
      quasiregular net has two kinds of natural tile and transitivity 1112.

PMID- 12496459
TI  - The crystallographic symmetry test for the correctness of a set of phases.
AB  - One of the most important problems in the application of direct methods for large
      structures is to establish reliable consistency criteria for the correctness of a
      phasing trial. The introduction in the twin variables method [Bethanis, Tzamalis,
      Hountas, Mishnev & Tsoucaris (2000). Acta Cryst. A56, 105-111] of a new criterion
      based on the crystallographic symmetry consists of testing the phase extension
      and refinement algorithm by deliberately sacrificing the space-group-symmetry
      information in the auxiliary variable set then using its gradual re-appearance as
      a criterion for correctness. In the present paper, the crystallographic symmetry
      test has been used in the implementation of the twin algorithm in two different
      ways: (i) as an overall test throughout the iterations that is likely to reflect
      the correctness of the phasing procedure for each one of the extension trials in
      a macromolecular phasing environment; (ii) as a convenient criterion to determine
      the optimum cycle for freeing the initial phases used by the algorithm for the
      phase-extension procedure.

PMID- 12496460
TI  - Analysis of voids in crystal structures: the methods of 'dual' crystal chemistry.
AB  - The theoretical basics of the analysis of voids in crystal structures by means of
      Voronoi-Dirichlet polyhedra (VDP) and of the graph theory are stated. Topological
      relations are considered between VDPs and atomic domains in a crystal field.
      These relations allow the separation of two non-intersecting topological
      subspaces in a crystal structure, whose connectednesses are defined by two finite
      'reduced' graphs. The first, 'direct', subspace includes the atoms (VDP centres)
      and the network of interatomic bonds (VDP faces), the second, 'dual', one
      comprises the void centres (VDP vertices) and the system of channels (VDP edges)
      between them. Computer methods of geometrical-topological analysis of the 'dual'
      subspace are developed and implemented within the program package TOPOS. They are
      designed for automatically restoring the system of channels, visualizing and
      sizing voids and void conglomerates, dimensional analysis of continuous void
      systems, and comparative topological analysis of 'dual' subspaces for various
      substances. The methods of analysis of 'dual' and 'direct' subspaces are noted to
      differ from each other only in some details that allows the term 'dual' crystal
      chemistry to be introduced. The efficiency of the methods is shown with the
      analysis of compounds of different chemical nature: simple substances, ionic
      structures, superionic conductors, zeolites, clathrates, organic supramolecular
      complexes.

PMID- 12496461
TI  - The generalized pendulum analogy of the X-ray dynamical diffraction by one
      dimensional regularly deformed crystals.
AB  - The pendulum analogy has been generalized in a form suitable for the case of an
      off-Bragg position. It is shown that, by introducing a time variation of the
      pendula masses, this analogy can be supplied to simulate the X-ray dynamical
      diffraction by a one-dimensional regularly deformed crystal. The correspondence
      between the adiabatic invariants of the new mechanical system and the invariants
      of the Eikonal approximation of the X-ray dynamical theory is established

PMID- 12496462
TI  - Domino phase-retrieval algorithm for structure determination using electron
      diffraction and high-resolution transmission electron microscopy patterns.
AB  - Direct-method formalism to determine atomic structures using electron diffraction
      data is here aimed at a general solution of the phase-retrieval problem,
      consequently combining electron diffraction (ED) and high-resolution transmission
      electron microscopy (HRTEM) patterns in a 'domino' fashion. While there are
      similarities to conventional (kinematical) direct methods, there remain major
      differences; in particular, owing to the dynamical effects in the data, the ED
      structure factors prove to be complex and then the positivity of the
      reconstructed electron density is no longer a valid constraint for 'dynamical'
      direct methods. Besides, owing to the dynamical effects, heavy atoms no longer
      dominantly contribute to the HRTEM images. Thus, the 'dynamical' direct-methods
      concept is based on the phase-retrieval algorithm utilizing both the dynamical ED
      and the HRTEM data. The fusion of the traditional direct-method technique, which
      is described here, allows realization of a full-phase restoration of complex
      structure factors. A numerical example, using the dynamical ED and HRTEM data for
      (Ga,In)(2)SnO(5) ceramic, shows that the method is capable of yielding a unique
      phase-retrieval solution. The clear sense is that the domino transform algorithm
      proposed works well and represents a valuable method for phasing diffraction
      patterns in electron structural crystallography using an experiment that is
      readily performed when the ED and HRTEM data are collected.

PMID- 12496463
TI  - Average unit cell for Penrose tiling and its Gaussian approximation.
AB  - In this paper, the average unit cell for a quasicrystal is constructed by a
      statistical approach. For the Penrose tiling, it is shown that such a unit cell
      is fully equivalent to the oblique projection of the atomic surface onto physical
      space. The obtained statistical distributions can be easily extended to imperfect
      structures by using a Gaussian approximation. This leads to simple analytical
      expressions for diffraction intensities, which can be very useful in structure
      refinement.

PMID- 12496464
TI  - On integrating the techniques of direct methods and SIRAS: the probabilistic
      theory of doublets and its applications.
AB  - The mathematical formalism of direct methods is here applied to the SIRAS (single
      isomorphous replacement combined with anomalous scattering) case. Specifically,
      the joint probability distribution of three structure factors, which plays the
      central role in the probabilistic theory of the two-phase structure invariants
      (doublets), is derived. This distribution leads directly to the conditional
      probability distribution of the two-phase structure invariants, given the values
      of selected sets of magnitudes. Furthermore, a probabilistic formula for
      estimating individual phases of the derivative structure is derived, provided
      that the heavy-atom substructure is assumed to be known. The formulas were tested
      for experimental SIRAS data and results are reported.

PMID- 12496469
TI  - Tumor microenvironment and the response to anticancer therapy.
AB  - Human solid tumors are invariably less well oxygenated than normal tissues. This
      leads to resistance to radiotherapy and anticancer chemotherapy, as well as
      predisposing for increased tumor metastases. Prolonged hypoxia of the tumor
      tissue also leads to necrosis, and necrotic regions are also characteristic of
      solid tumors. These two characteristics-hypoxia and necrosis-represent clear
      differences between tumors and normal tissues and are potentially exploitable in
      cancer treatment. This review focuses on the phenomenon of tumor hypoxia and how
      hypoxia and its accompanying necrosis can be exploited in therapy. One such
      strategy is to use drugs that are toxic only under hypoxic conditions, and the
      first drug of this class to enter clinical testing, tirapazamine, is showing
      considerable promise. The second way to exploit hypoxia is to take advantage of
      the selective induction under hypoxia of the transcription factor HIF-1 (hypoxia
      inducible factor 1). Gene therapy strategies based on this are in development.
      Finally, tumor hypoxia can be exploited using live obligate anaerobes that have
      been genetically engineered to express enzymes that can activate non-toxic
      prodrugs into toxic chemotherapeutic agents.

PMID- 12496470
TI  - Cellular adhesion pathways and metastatic potential of human melanoma.
AB  - Cellular adhesion molecules of the cadherin, integrin, and immunoglobulin
      superfamilies are important to both growth and metastasis of many cancers,
      including malignant melanoma. Malignant melanoma is an excellent model for
      studying these molecules, due in part to a sequential series of five defineable
      stages. As the malignant phenotype of melanoma cells changes from the noninvasive
      radial growth phase to the vertical growth phase, which has high metastatic
      potential, so does the repertoire of the cellular adhesion molecules expressed on
      the cells surface. The cellular adhesion molecule MCAM/MUC18 confers metastatic
      potential and increased tumorigenicity to melanoma cells. MCAM/MUC18 mediates
      homotypic and heterotypic adhesion between melanoma cells and endothelial cells,
      respectively. Both types of interaction may promote metastasis at different
      stages in the metastasis cascade. We developed a fully humanized antibody to
      MCAM/MUC18 (ABX-MA1) that blocked melanoma metastasis in vivo. Furthermore, ABX
      MA1 blocked the homotypic interaction between melanoma cells and endothelial
      cells as well as the promoter and collagenase activity of MMP-2. During melanoma
      progression the loss of E-cadherin expression disrupts normal homeostasis in the
      skin by freeing melanoma cells from structural and functional regulation by
      keratinocytes. The loss of functional E-cadherin is parallelled by a gain in N
      cadherin function that mediates homotypic interaction between melanoma cells,
      facilitates gap-junctional formation with fibroblasts and endothelial cells and
      promotes melanoma cell migration and survival. In addition, loss of E-cadherin
      may affect the beta-catenin/wnt signaling pathways, resulting in deregulation of
      genes involved in growth and metastasis. The integrin family member
      alpha(v)beta(3) is widely expressed on melanoma cells in the vertical growth
      phase. When alpha(v)beta(3) is expressed in melanoma cells in the radial growth
      phase, this integrin is associated with increased tumor growth in vivo.
      alpha(v)beta(3) may also promote melanoma invasion, through an interaction with
      MMP-2, and transendothelial migration, via a heterotypic melanomaendothelial cell
      interaction. This review summarizes recent knowledge on how changes in these
      adhesion molecules contribute to the acquisition of the metastatic phenotype in
      human melanoma.

PMID- 12496471
TI  - Notch signaling in cancer.
AB  - Notch signaling plays a key role in the normal development of many tissues and
      cell types, through diverse effects on differentiation, survival, and/or
      proliferation that are highly dependent on signal strength and cellular context.
      Because perturbations in the regulation of differentiation, survival, and/or
      proliferation underlie malignant transformation, pathophysiologic Notch signals
      potentially contribute to cancer development in several different ways. Notch
      signaling was first linked to tumorigenesis through identification of a recurrent
      t(7;9)(q34;q34.3) chromosomal translocation involving the human Notch1 gene that
      is found in a small subset of human pre-T-cell acute lymphoblastic leukemias (T
      ALL).(1) Since this discovery, aberrant Notch signaling has been suggested to be
      involved in a wide variety of human neoplasms. In this review, we will focus on
      recent studies linking aberrant Notch signaling with cancer. First, we discuss
      various mechanisms through which Notch signaling may influence cellular
      transformation. Then, we critically review literature pertaining to the role of
      Notch signaling in several cancers, and discuss possible therapeutic targets in
      the Notch pathway.

PMID- 12496472
TI  - DNA repair and tumorigenesis: lessons from hereditary cancer syndromes.
AB  - The discovery that alterations of the DNA mismatch repair system (MMR) were
      linked to the common human cancer susceptibility syndrome hereditary nonpolyposis
      colon cancer (HNPCC) resulted in the declaration of a third class of genes
      involved in tumor development. In addition to oncogenes and tumor suppressors,
      alterations of DNA repair genes involved in maintaining genomic stability were
      found to be a clear cause of tum the level of the single nucleotides or
      chromosomes. This observation suggested that the establishment of genomic
      instability, termed the Mutator Phenotype, was an important aspect of tumor
      development.(1,2) Since the initial identification of the human MutS homolog
      hMSH2 nearly a decade ago,(3,4) more links have been described between human
      cancers and genes involved in maintaining genomic stability. Work in recent years
      has revealed that DNA repair proteins may also function in signaling pathways
      that provoke cell cycle arrest and apoptosis. This review will focus on the
      genetic and biochemical functions of DNA repair genes linked to hereditary cancer
      predisposition characterized by genomic instability (Table 1). Interestingly, the
      protein products of these genes have been directly or indirectly linked to the
      DNA damage-induce cell cycle arrest and apoptosis. We conclude that a robust
      connection between DNA repair proteins and damage-induced apoptosis may be as
      important for tumorigenesis as their role in maintaining genome stability.

PMID- 12496473
TI  - Flt-3 ligand: a potent dendritic cell stimulator and novel antitumor agent.
AB  - Dendritic cell (DC) vaccination has generated intense interest as a potential
      cancer therapy. However, the rate limiting step has been the generation of DCs.
      Flt-3 ligand (FL) is a growth factor that was first discovered by its ability to
      stimulate the proliferation of hematopoietic progenitor cells of both lymphoid
      and myeloid origin. The remarkable activity of FL to induce large numbers of
      dendritic cells both in vivo and in vitro soon captured the interest of numerous
      researchers. In this review, we examine the structure and function of the FL, its
      antitumor activity in animal models, and its potential as a novel cancer
      treatment.

PMID- 12496474
TI  - Transactivation of repair genes by BRCA1.
AB  - Recent studies have identified a link between the BRCA1 tumor suppressor and
      transcriptional regulation of a group of genes involved in nucleotide excision
      repair. There is some controversy regarding the precise mechanism of upregulation
      of XPE DDB2 or XPC by BRCA1, with some evidence suggesting that p53 is involved
      in their regulation. Some evidence suggests BRCA1 may stabilize p53 and direct
      regulation of DNA repair genes, although how BRCA1 stabilizes p53 remains unclear
      and whether BRCA1 can upregulate DNA repair genes in a p53-independent manner
      remains a possibility. A transcriptional component to the action of BRCA1 and
      involvement of XP genes brings up new and interesting questions about breast
      cancer development and therapy.

PMID- 12496475
TI  - c-Myc overcomes cell cycle inhibition by CBFbeta-SMMHC, a myeloid leukemia
      oncoprotein.
AB  - Thirty percent of acute myeloid leukemia cases express a Core Binding Factor
      (CBF) oncoprotein or harbor point mutations in one or both AML1 (RUNX1) genes.
      Each of these alterations reduces endogenous CBF activities. CBFbeta-SMMHC is
      expressed from the inv(16) chromosome in 8% of AML cases and inhibits endogenous
      CBF DNA-binding. Inhibition of CBF reduces Retinoblastoma protein phosphorylation
      and slows the G(1) to S cell cycle transition. c-Myc, a protein which stimulates
      S phase entry, is over-expressed in one-third of AMLs. We have developed Ba/F3
      cell lines in which zinc regulates CBFbeta-SMMHC expression and 4
      hydroxytamoxifen activates c-Myc-ER. In these lines, c-Myc-ER overcomes
      inhibition of cell cycle progression mediated by CBFbeta-SMMHC. CBFbeta-SMMHC
      does not affect endogenous c-Myc RNA levels, indicating that CBF does not
      regulate the c-Myc gene. Conversely, c-Myc-ER does not alter CBF DNA-binding
      activity. Thus, c-Myc-ER acts downstream of CBFbeta-SMMHC to stimulate cell cycle
      progression. In a subset of CBF leukemias, elevated expression of c-Myc is
      expected to facilitate the proliferation of the leukemic blasts and thereby
      potentiate the ability of CBF oncoproteins to block differentiation.

PMID- 12496476
TI  - A naturally occurring allele of BRCA1 coding for a temperature-sensitive mutant
      protein.
AB  - Recent evidence suggests that the breast and ovarian cancer susceptibility gene
      product BRCA1 is involved in at least two fundamental cellular processes:
      transcriptional regulation and DNA repair. However, the mechanism of action of
      BRCA1 in either of these processes is still unknown. Here, we report the
      characterization of a disease-predisposing allele of BRCA1, identified in a
      family with several cases of ovarian cancer, coding for a protein that displays
      temperature-sensitive activity in transcriptional activation. The mutant protein
      differs from the wild type protein at a single amino acid, R1699W that occurs in
      a region at the N-terminal BRCT domain that is highly conserved among BRCA1
      homologs. When the C-terminus of the mutant protein (aa 1560-1863) was fused to a
      heterologous GAL4 DNA-binding domain and expressed in yeast or mammalian cells,
      it was able to activate transcription of a reporter gene to levels observed for
      wild type BRCA1 at the permissive temperature (30 degrees C) but exhibited
      significantly less transcription activity at the restrictive temperature (37
      degrees C or 39 degrees C). Our results indicate that the transcriptional
      activity of the R1699W mutant can be modulated as a function of temperature and
      provide a novel experimental approach which can be utilized to dissect the
      molecular mechanism(s) of BRCA1 in processes related to transcription.

PMID- 12496477
TI  - Mutations in the BRCT domain confer temperature sensitivity to BRCA1 in
      transcription activation.
AB  - BRCA1 is a tumor suppressor gene and germ line mutations account for the majority
      of familial cases of breast and ovarian cancer. There is mounting evidence that
      BRCA1 functions in DNA repair and transcriptional regulation. A major hurdle to
      dissect the role of BRCA1 is the lack of molecular reagents to carry out
      biochemical and genetic experiments. Therefore, we used random mutagenesis of the
      C-terminus of BRCA1 (aa 1560-1863) to generate temperature-sensitive (TS) mutants
      in transcription activation. We obtained 11 TS mutants in transcription that
      localized primarily to the hydrophobic core of the BRCT-N domain of BRCA1. One of
      the mutants, H1686Q, also displayed temperature-dependent transcription
      activation in human cells. These conditional mutants represent valuable tools to
      assess the role of BRCA1 in transcription activation.

PMID- 12496478
TI  - Creating a tool-kit for exploring BRCA1 function.

PMID- 12496479
TI  - p53 null mutations are associated with a telomerase negative phenotype in ovarian
      carcinoma.
AB  - Telomerase activation and p53 dysfunction are important events in the development
      and progression of most cancers including ovarian cancer. However, many cancer
      cell lines and human tumors have been shown to lack telomerase, and maintain
      telomerase through the ALT (alternative lengthening of telomeres). It is not
      known whether specific types of p53 mutations are correlated with telomerase
      activity in human tumors. Invasive ovarian cancers (109) were analyzed for
      telomerase by ELISA and its subunits human telomerase RNA (hTR), and human
      telomerase reverse transcriptase (hTERT) by RT-PCR. p53 protein was analyzed in
      the same samples using immunohistochemistry, and p53 exons 2-11 were analyzed
      using SSCP and sequence analysis. Telomerase activity was detected in 80 (74%) of
      109 tumors. The subunit hTR was consistently present in all ovarian cancer
      samples, and hTERT was expressed in 96 (88%) tumors. Thirteen (16%) tumors were
      negative for hTERT and none of these expressed telomerase. Fifty-seven (52%)
      tumors stained positive for p53, and there was no correlation with telomerase
      activity based on p53 staining (p = 0.08). Eighty-two (75%) tumors were found to
      have a p53 mutation, and 40 (36%) tumors contained a null mutation. Only 14% of
      the tumors with wild type or missense p53 were negative for telomerase activity.
      In contrast, 19 (48%) of 40 tumors with a p53 null mutation were negative for
      telomerase activity (p <0.001). There was no difference in the incidence of
      telomerase positivity between critical site versus non-critical site missense p53
      mutations. Seventy-five percent of the tumors with a p53 mutation in the central
      region were telomerase positive. In contrast, only 47% of the tumors with a
      mutation in either the amino- or carboxy-terminus were telomerase positive (p =
      0.03). Ovarian cancers with a p53 null mutation are more likely to lack
      telomerase activity. This may have implications for therapeutic approaches based
      on telomerase.

PMID- 12496480
TI  - p53: a key player in the telomere dynamics.

PMID- 12496481
TI  - Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced
      apoptosis which correlates with the loss of c-FLIP expression.
AB  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL/Apo2L) can induce
      receptor-mediated apoptosis in prostate cancer cell lines that have been co
      treated with the chemotherapeutic agent doxorubicin (Voelkel-Johnson C, et al.
      Cancer Gene Therapy 2002; 9:164-172). In this study, we report that pretreatment
      with doxorubicin is sufficient to sensitize cells to TRAIL. To identify possible
      targets of doxorubicin, we analyzed levels of several Bcl-2 family members, TRAIL
      receptors and the anti-apoptotic protein c-FLIP. Doxorubicin did not affect
      steady state levels of Bax, Bcl-2 and Bcl-X(L) in the majority of the prostate
      cancer cell lines. TRAIL receptor mRNAs (DR4, DR5, and DcR2) were induced by
      doxorubicin but these changes were not reflected at the protein level. In
      contrast, in response to doxorubicin, levels of c-FLIP, particularly FLIP(S),
      decreased in all cell lines tested. The decrease in c-FLIP(S) correlated with
      onset and magnitude of caspase-8 and PARP cleavage in PC3 cells. In two TRAIL
      resistant cell lines, DU145 and LNCaP, treatment with TRAIL alone resulted in
      processing of c-FLIP(L) and initiated abortive caspase-8 proteolysis. TRAIL
      treatment did not affect levels of c-FLIP(S) in Du145 and LNCaP cells and did not
      result in PARP cleavage. Therefore, our results suggest that doxorubicin-
      mediated down regulation of c-FLIP(S) predisposes cells to TRAIL-induced
      apoptosis.

PMID- 12496482
TI  - The FLIP variation on the TRAIL DISC: doxorubicin conducts the swan song.

PMID- 12496483
TI  - Mismatch repair gene mutations in renal cell carcinoma.
AB  - We investigated the spectrum and genetic basis for mismatch repair (MMR)
      deficiency in renal cell carcinoma (RCC) by examining expression of four MMR
      genes important for hereditary and sporadic carcinogenesis. MMR deficiency was
      assessed using microsatellite instability (MSI) and genetic analyses of 25 cell
      lines derived from renal tumors. MMR gene alterations were detected using reverse
      transcription of RNA coupled with polymerase chain reaction (RT-PCR) and DNA
      sequencing. Three RCC lines with undetectable MLH1 were identified and
      investigated for MSI and inactivating mutations in the hMLH1 MMR gene. Genetic
      instability and hMLH1 mutations were identified in two RCC lines and their
      corresponding tumors. Genetic alterations affecting expression were limited to
      MLH1 since other MMR proteins (MSH2, MSH6 and PMS2) were detectable in our RCC
      lines. Complete inactivation of MMR is apparently uncommon in RCC and occurs
      predominantly through inactivating mutations in the hMLH1 gene.

PMID- 12496484
TI  - Renal cell carcinoma: taking care of business.

PMID- 12496485
TI  - Didox (a novel ribonucleotide reductase inhibitor) overcomes Bcl-2 mediated
      radiation resistance in prostate cancer cell line PC-3.
AB  - In this study, we investigated the influence of Bcl-2 overexpression on the
      radiosensitizing potential of Didox (DX; 3,4-Dihydroxybenzohydroxamic acid), a
      novel ribonucleotide reductase inhibitor, in p53-null prostate cancer cell line
      PC-3. The PC-3 cells were transfected with vector alone or ectopically
      overexpressed with CMV-Bcl-2 construct. The effect of radiation (IR) or DX alone
      and in combination (pre and post IR exposure of DX) on cell survival was
      determined by colony-forming assay. The impact of these two treatments on the
      cell cycle was determined by flow cytometry. To further understand the molecular
      mechanism of DX-mediated radiosensitization, induction of pro-survival and pro
      apoptotic factors were determined by Western blot and gel-shift assays
      respectively. When compared to PC-3/Bcl-2 cells (SF(2)=0.84; D(0)=437cGy), the PC
      3/vector cells (SF(2)=0.4; D(0)=235cGy) were significantly sensitive to ionizing
      radiation (p<0.001). Exposure of DX at 5 microM concentration prior or post to
      radiation in both PC-3/vector and PC-3/Bcl-2 transfectants caused an increase in
      radiation enhancement ratios. A significant reduction in G(2)M phase was observed
      in cells exposed to DX post IR when compared to cells exposed to IR alone.
      Exposure to DX after radiation in PC-3/vector significantly abrogated radiation
      induced Bcl-2 upregulation, with a concomitant induction of bax protein. In PC
      3/Bcl-2 transfectants, DX exposure after IR caused an induction of bax protein.
      Gel shift assays indicated that in PC-3/vector cells when exposed to IR caused an
      induction of NFkappa-B activity however, DX down regulated the NFkappa-B
      activity. Radiation-induced NFkappa-B activity was abrogated in pre and post DX
      exposure in combination with IR. These findings indicate that DX mediates a
      potent radiosensitizing effect in p53 null prostate cancer cells by overcoming
      radiation induced NFkappa-B activity and Bcl-2 expression.

PMID- 12496486
TI  - Ribonucleotide reductase inhibition: regulation of the radiosensitive phenotype
      via NF kappa B and Bcl-2.

PMID- 12496487
TI  - Gene therapy of prostate cancer with the soluble vascular endothelial growth
      factor receptor Flk1.
AB  - A variety of novel therapeutic approaches have emerged recently for the treatment
      of human cancers. We have coupled two of these therapeutic approaches, gene
      therapy and antiangiogenic therapy and tested them in two murine prostate cancer
      models Recombinant adenovirus encoding the ligand-binding ectodomain of the VEGF
      receptor 2 (Flk1) fused to an Fc domain was administered to SCID mice carrying
      orthotopic human LNCaP tumors as well as to transgenic (TRAMP) mice with
      spontaneous prostate tumors. Ad Flk1-Fc injection reduced tumor growth by 66% for
      orthotopic LNCaP tumors and by 42% for spontaneous tumors in TRAMP mice.
      Microvessel density in the primary tumors was reduced by 68% and 40% in the two
      models respectively. A decrease in microvessel density was also observed in
      lymphatic metastases in Ad Flk1-Fc-treated TRAMP mice and was correlated with a
      decrease in the frequency of regional metastases in the treated animals. Survival
      time was also extended in the Ad Flk1-Fc-treated TRAMP mice relative to the
      control-treated animals. Our results suggest that adenoviral delivery of soluble
      Flk1 receptor can reduce vascular density and prostate tumor growth and prolong
      survival time in orthotopically implanted tumors as well as in spontaneous
      prostate tumors in transgenic animals.

PMID- 12496488
TI  - Modeling antiangiogenesis gene therapy.

PMID- 12496489
TI  - IL-10/IL-10 receptor signaling regulates TIMP-1 expression in primary human
      prostate tumor lines.
AB  - An IL-10 responsive signal protein, termed IL-10E1, was cloned from human
      prostate cancer PC-3 ML cells based on its binding affinity for a novel enhancer
      element (i.e., HTE-1: 5'-CACGATGACTCATCACTGTTGAAAGACA-3') of the Tissue Inhibitor
      of metalloproteinase-1 (TIMP-1) gene. Electrophoretic mobility shift assays
      (EMSAs) and enzyme linked immuno-sandwich assays (ELISAs) showed that IL-10
      stimulated the rapid translocation of IL-10E1 to the nucleus and the activation
      of TIMP-1 expression in 4 different androgen dependent primary prostate tumor
      lines generated in our laboratory (i.e. HPCA-5a, 5b, 5c and 5d lines). IL-10
      signaling was blocked by a variety of agents, including IL-10 receptor
      antibodies, alpha-toxin, and Genistein. The inhibition of IL-10 signaling and IL
      10E1 expression correlated directly with a significant decrease in TIMP-1
      expression by the HPCA-5a, 5b, 5c and 5d cell lines. Following permanent
      transfection of HPCA-5a and 5c cells with the IL-10 gene the growth of tumor
      xenografts in SCID CB17 mice was severely retarded, yielding tiny, poorly
      vascularized tumors by approximately 90 days post-inoculation s.c. ELISAs showed
      that these tumors expressed elevated levels of IL-10, IL-10E1 and TIMP-1 compared
      with tumors from non-transfected or Mock transfected cell lines. We conclude that
      the IL-10/IL-10 receptor axis (and IL-10E1 signaling) regulation of TIMP-1
      expression plays a key role in inhibiting tumor growth, perhaps by blocking tumor
      vascularization.

PMID- 12496490
TI  - Understanding the cancer biology universe: enigmas, context and future prospects.

PMID- 12496491
TI  - The changing complexion of America's academic research enterprise.

PMID- 12496492
TI  - Whose hypothesis? Ciphering, sectorials, D lesions, freckles and the operation of
      Stigler's Law.
AB  - Common references to the famous two-hit hypothesis of tumorigenesis are
      pervasively erroneous, and the recited tenets of this model vary enormously.
      Exploration of the history of this model reveals a rich philosophical progression
      that profited from perceptive observations, clever musings, and rediscoveries by
      many investigators over a period of decades. The current work is intended to
      raise the appreciation for this rich history and to address some of the more
      common errors.

PMID- 12496493
TI  - Shifting paradigms in tumor metastasis: challenges and opportunities.

PMID- 12496495
TI  - T wave alternans for ventricular arrhythmia risk stratification.
AB  - Sudden cardiac death remains one of the leading causes of death in western
      societies. Accordingly, the ability to identify patients at high risk of sudden
      cardiac death is important so that appropriate treatments can be used
      efficiently. Recently, T wave alternans (TWA) has emerged as a promising new test
      for such risk stratification. TWA is a heart rate-dependent measure of arrhythmia
      vulnerability, with maximal predictive accuracy at sustained, regular heart rates
      of 100 to 120 bpm. In the clinical setting, these conditions may be achieved by
      either exercise or atrial pacing. TWA has been shown to predict inducibility of
      ventricular tachycardia with programmed stimulation and also spontaneous
      arrhythmic events. TWA has been successfully applied to diverse populations,
      including patients with coronary artery disease, nonischemic cardiomyopathy,
      congestive heart failure, and implantable defibrillators. Despite these
      encouraging results, the role of TWA to guide clinical therapy still needs to be
      elucidated better.

PMID- 12496496
TI  - Torsade de pointes.
AB  - Torsade de pointes ventricular tachyarrhythmia in the long QT syndrome is a prime
      example of how molecular biology, ion channel, and cellular and organ physiology,
      coupled with clinical observations, promise to be the future paradigm for
      advancement of medical knowledge. Both the congenital and the acquired long QT
      syndrome are caused by abnormalities (intrinsic, acquired, or both) of the ionic
      currents underlying ventricular repolarization. In this review, the continually
      unraveling molecular biology of congenital long QT syndrome is discussed. The
      various pharmacologic agents associated with the acquired long QT syndrome are
      listed. Although it is difficult to predict which patients are at risk for
      torsade de pointes, careful assessment of the risk to benefit ratio is important
      before prescribing drugs known to cause QT prolongation. The in vivo
      electrophysiologic mechanism of torsade de pointes in the long QT syndrome is
      described, using as a paradigm the anthopleurin-A canine model, a surrogate for
      LQT3. The characteristic association of torsade de pointes with T-wave alternans
      and short-long cardiac sequences is discussed, with emphasis on
      electrophysiologic mechanisms. Finally, the expanding knowledge of genetic
      mutations other than long QT syndrome associated with polymorphic ventricular
      tachyarrhythmia is emphasized.

PMID- 12496497
TI  - Update on cardiac resuscitation for sudden death: International Guidelines 2000
      on Resuscitation and Emergency Cardiac Care.
AB  - Cardiopulmonary resuscitation developed over the past one half century largely
      from empiric science and consensus opinions and recommendations. Treatment
      algorithms and protocols were originally developed to summarize existing
      recommendations for systematic and regimented use by a heterogenous group of
      health care providers. Now, resuscitation science and health care teams are
      focusing on major issues and continuing questions as sudden death rates remain
      undaunted and the population at risk is rapidly increasing. For the first time,
      the international resuscitation community has developed an international
      consensus on Guidelines for Resuscitation and Emergency Cardiac Care. More than
      400 basic scientists, clinical trial investigators, and educators defined common
      priority and scientific areas during the Evidence Evaluation International
      Meeting in 1999. The science of resuscitation and emergency cardiac care was
      reviewed for evidence-based support in randomized clinical trials. In 2000, this
      review was used as a foundation to structure international guidelines. The
      participants from seven resuscitation councils and foundations realized that
      regional differences in systems may exist, but the underlying science should be
      the same. Presented in this article are some of the major issues and
      controversies discussed in adult advanced cardiac life support, primarily
      focusing on the major problem of prehospital adult cardiac arrest.

PMID- 12496498
TI  - Anticoagulation in management of atrial fibrillation.
AB  - Atrial fibrillation is the most common cardiac arrhythmia in adults. The
      prevalence of atrial fibrillation rises with age, reaching as high as 9% in those
      70 years and older. Currently there are 2.2 million affected people in the United
      States, with twice the mortality rate of age-matched controls in sinus rhythm.
      Epidemiologic studies show atrial fibrillation to be responsible for as many as
      15% of the total number of strokes, a higher incidence of dementia, cardiac
      function compromise, and decreased quality of life. Recent studies indicate that
      rate control and rhythm restoration are equally effective strategies in the
      treatment of atrial fibrillation, with a trend toward better survival in patients
      treated for rate control and anticoagulation. Data from several randomized
      controlled studies on stroke prophylaxis provided consistent evidence of the
      superiority of adjusted-dose warfarin over aspirin. Guidelines developed by the
      American College of Cardiology, the American Heart Association, the European
      Society of Cardiology, and ACCP provide a convenient decision-making framework
      for the practicing physician. The safety and effectiveness of anticoagulation in
      clinical practice were found to be equal to those in major trials with rigorous
      controls. Despite the proven effectiveness and safety of oral anticoagulation for
      thromboembolism prophylaxis in atrial fibrillation, warfarin remains underused,
      especially among the elderly (75 years and older), who are at the greatest risk
      of stroke and would likely benefit the most from prophylactic anticoagulation.

PMID- 12496499
TI  - Atrial fibrillation in patients with heart failure.
AB  - Atrial fibrillation and heart failure are very common cardiac disorders, and both
      are associated with symptoms, significant morbidity, and mortality. Studies have
      attempted to determine the prognostic significance of atrial fibrillation in
      patients with heart failure. Whether atrial fibrillation is an independent risk
      factor of mortality remains controversial. Multiple trials using either
      pharmacologic or nonpharmacologic therapies in an attempt to manage atrial
      fibrillation have been developed. The purposes of this review are to present an
      overview of atrial fibrillation in patients with heart failure and to discuss the
      prevalence, prognostic significance, complications, mechanisms, and trials that
      have formed the therapies presently used.

PMID- 12496500
TI  - Pulmonary vein ablation: role in preventing atrial fibrillation.
AB  - Several investigators have identified the pulmonary vein as the most common
      initiator of atrial fibrillation, and isolation of the pulmonary vein from atrial
      tissue can cure approximately 70% of patients with paroxysmal atrial
      fibrillation. Ongoing trials of a new device may increase the success rate and
      decrease the complication rate during the pulmonary vein isolation procedure.

PMID- 12496501
TI  - Role of pacemakers in treating neurocardiogenic syncope.
AB  - Patients with frequent vasovagal syncope have a poor quality of life and often
      resist treatment with standard pharmacologic approaches. Clinical vasovagal
      syncope may be associated with some degree of bradycardia. Studies of temporary
      pacing during tilt table tests showed that pacing prevented syncope in a little
      more than half of patients who developed a vasovagal response. Six open-label
      studies of permanent pacing show that permanent pacemaker therapy is associated
      with substantial improvement over medical therapy. The roles of specific
      pacemaker modes have not been determined, although there is some evidence that
      rate-drop responsiveness helps. The second Vasovagal Pacemaker Study will
      quantify the true benefits of pacing for vasovagal syncope and assess the role of
      rate-drop response algorithms.

PMID- 12496503
TI  - Biologic therapies in the vasculitides.
AB  - Monoclonal antibody and recombinant DNA technologies have led to the development
      of biologic therapies capable of directly targeting selected components of the
      immune response. With the steady expansion of knowledge regarding the mechanisms
      of vascular inflammation, the safety and efficacy of biologic agents in the
      vasculitic diseases are being increasingly investigated. By targeting specific
      effector mechanisms involved in the pathogenesis of vasculitis, these agents may
      provide a less toxic means of inducing remission and lessening relapse. However,
      the study of biologic therapies in the vasculitides must be approached with
      caution, as unanticipated effects on disease activity and disease-specific
      toxicities can occur. Studies to examine these agents must recognize the
      potential for active vasculitis to be organ- or life-threatening as well as the
      current existence of effective therapies. In the research setting, investigation
      of biologic agents in the treatment of vasculitic diseases may also provide
      important insights into pathogenesis of these syndromes.

PMID- 12496504
TI  - Epidemiology of the vasculitides.
AB  - The past year has seen some notable publications in the field of vasculitis
      epidemiology. The appearance of reports from several different parts of the world
      has permitted comparisons to be made. In Europe, Wegener granulomatosis appears
      to be more common at high latitudes, whereas microscopic polyangiitis shows the
      reverse pattern. Kawasaki disease is most common in Japan. In China, the United
      States, and the United Kingdom, the incidence is lower, but the incidence appears
      to be increasing globally. Studies of infectious triggers continue to be
      disappointingly negative. Immunogenetic associations with cytokine polymorphisms
      are beginning to be reported.

PMID- 12496505
TI  - Glomerulonephritis in the vasculitides: advances in immunopathology.
AB  - Systemic vasculitis refers to a condition of blood vessel inflammation, of which
      the causes are various. In a substantial number of cases, autoantibodies against
      neutrophil cytoplasm constituents (ANCAs) are present. The authors then refer to
      the systemic vasculitis as ANCA-associated systemic vasculitis. Renal disease is
      an unfavorable component, leading to dialysis dependency in a considerable number
      of patients. This review aims to summarize in brief what was reported about ANCA
      associated vasculitis in the recent past. What the exact pathogenic role of ANCAs
      in the development of systemic vasculitis is remains uncertain, and it is still
      not clear how their presence leads to the histopathologic lesions called
      vasculitis.

PMID- 12496506
TI  - Organ transplantation in the vasculitides.
AB  - Despite important therapeutic improvements, permanent organ failure may develop
      in primary systemic vasculitides and affect the heart, the lungs, and especially
      the kidneys. In systemic vasculitides associated with antineutrophil cytoplasmic
      antibodies (AASV), end-stage renal failure develops in 20% of cases. Renal
      transplantation became a beneficial option in these patients, with a graft and
      patient survival comparable to that in nondiabetic patients. This review
      summarizes the current knowledge on indications and contraindications for renal
      transplantation in AASV and discusses the impact of posttransplant
      immunosuppression on the course of the patients.

PMID- 12496507
TI  - Think clearly, be sincere, act calmly: Adolf Kussmaul (February 22, 1822-May 28,
      1902) and his relevance to medicine in the 21st century.
AB  - This past year, 2002, marked the 100th anniversary of the death of Adolf
      Kussmaul. To rheumatologists, he is important as the author of the first case of
      idiopathic vasculitis, polyarteritis nodosa, which even today is the basis of our
      understanding of vasculitis. To general internists, his name is linked to
      Kussmaul's sign and Kussmaul breathing, and to gastroenterologists, he is in many
      ways-through the development of the gastric pump and the first gastroscope-the
      father of modern gastroenterology. His reputation as an excellent teacher, his
      compassion for his patients, and his ability as a clinician scientist led him to
      be regarded as a giant of 19th century medicine. Kussmaul's life and career,
      dedicated foremost to reducing human suffering and advancing medicine as a
      scientific discipline with a strong humanistic foundation, make him a role model
      for physicians of today.

PMID- 12496508
TI  - Rheumatic syndromes associated with malignancy.
AB  - The relation between rheumatic syndromes and an underlying malignancy is a
      complex one. As a result of autoimmunity, an aberrant immune response, or the use
      of immunomodulatory drugs, many of the rheumatic diseases appear to pose an
      increased risk for the development of malignancy. Unfortunately, for many of the
      same reasons, the presence of an underlying malignancy can result in the
      development of features of rheumatic disease. Awareness of the associations
      between rheumatic syndromes and malignancy will aid the clinician in the accurate
      diagnosis of underlying pathology, more effective treatment of both the symptoms
      and underlying disease, and appropriate surveillance for the development of later
      complications.

PMID- 12496509
TI  - Musculoskeletal manifestations of hemoglobinopathies.
AB  - Patients with sickle cell disease often seek treatment for rapid periorbital
      swelling due to infarction of the orbital bones. Because of resulting orbital
      compression syndrome, treatment with corticosteroids and antibiotics is
      advisable. If spinal tuberculosis occurs in patients with sickle cell anemia,
      radiologic signs will be a combination of the two conditions. The diagnosis of
      juvenile rheumatoid arthritis is usually delayed in patients with sickle cell
      disease. Sulphasalazine is the disease-modifying drug of choice for treating
      juvenile rheumatoid arthritis, because it also reduces the adhesiveness of
      sickled red cells. TNF-alpha inhibitors may also be useful for treating these
      patients. A volumetric method to determine the size and special distribution of
      the necrotic lesions of the femoral head has been developed using magnetic
      resonance imaging scans. With this method it will be easier to determine which
      early lesions require core decompression, or which ones should be treated
      conservatively. Osteomyelitis can be differentiated from bone infarction with the
      use of segmental radionuclide bone-marrow and bone scans. Reduction in frequency
      of painful crises can be achieved by increasing fetal hemoglobin with the use of
      hydroxyurea. The treatment of the actual pain requires decisions about the
      analgesics that are used as well as the route of their administration. Ketorolac
      monotherapy is likely to fail in the presence of an initial high pain score or
      with involvement of four or more pain sites.

PMID- 12496510
TI  - Musculoskeletal manifestations of chronic renal failure.
AB  - Musculoskeletal problems remain among the main limitations of the quality of life
      of renal failure patients, in particular of those treated with long-term
      maintenance dialysis. Renal osteodystrophy continues to receive great attention.
      The mechanisms of uremic skeletal resistance to parathormone (PTH) are further
      investigated. The assay used for the dosage of "intact PTH" has been found to
      detect 7-84 fragments with an inhibitory effect on the action of the whole
      hormone. A decrease in the density of PTH receptor on osteoblasts is another
      recently evidenced factor. Investigations of the recently described RANK-RANKL
      system have demonstrated an increase in serum osteprotegerin levels, which,
      together with the two above-mentioned abnormalities, may explain bone resistance
      to PTH. These are important advances in the understanding of renal osteodystrophy
      as skeletal resistance to PTH appears to play an important part in the
      pathophysiology of secondary hyperparathyroidism and of adynamic bone disease.
      Because of this skeletal resistance, it has been recommended for several years
      that serum PTH level be monitored and kept twofold to threefold above the upper
      value of the normal level to maintain normal bone turnover in dialysis patients.
      Relative hypoparathyroidism has recently been found to be associated with
      increased spontaneous fracture rate and mortality, so this recommendation appears
      to hold adequate, despite the demonstration that serum PTH levels in this range
      are a poor predictor of bone turnover and that chronic parathyroid gland
      hyperplasia is likely to favor parathyroid gland autonomization. Recent
      publications have insisted on the role that hyperphosphatemia plays not only in
      the development of secondary hyperparathyroidism, but also of vascular,
      especially coronary, calcification and as a predictor of mortality. This "silent
      killer" of uremic patients is one of the main targets for therapeutic
      intervention. Extensive use of calcium-containing phosphate binders has been
      recently criticized as calcium overload appears to favor vascular calcification.
      Sevelaner (RenaGel) is a calcium- and aluminum-free phosphate binder that is an
      important advance in the management of renal osteodystrophy, especially in
      patients with extraskeletal calcification and hypercalcemia. The use of vitamin D
      derivatives has also raised concern because they enhance calcium and phosphorus
      absorption and reduce bone turnover. New metabolites with fewer hypercalcemic
      effects have been developed. Calcium-sensing receptor agonists are stimulating
      interest and are likely to take an important place in the future management of
      renal osteodystrophy. Uremic myopathy has received recent attention. Impaired
      muscle capillary oxygen transfer has been identified as a pathophysiologic
      factor, and progressive resistance training has been shown to improve the
      condition. Finally, a new entity, nephrogenic fibrosing dermopathy, has been
      described, which must be distinguished from calciphylaxis and scleromyxedema.

PMID- 12496511
TI  - Rheumatic syndromes associated with complement deficiency.
AB  - Deficiency of an early component of the classical complement pathway, C1q,
      C1r/C1s, C4, or C2, regularly produces autoimmunity in man, especially systemic
      lupus erythematosus. It has long been suggested that disruption of this pathway
      would lead to the inappropriate handling of immune complexes. An intriguing
      hypothesis that builds on this idea relates to a defect in clearance of one's own
      cellular debris, namely apoptotic cells. An attractive feature of this emerging
      concept is that blebs on apoptotic cells are decorated with antigens to which
      much of the autoantibody specificity is directed in systemic lupus erythematosus.
      A second hypothesis, generated primarily from complement deficiencies, relates to
      an impairment in the humoral immune response or in the regulation of autoreactive
      B cells. This review begins by summarizing the recognized autoimmune
      manifestations of complement deficiency and then describes new data derived from
      targeted gene deletions of complement proteins.

PMID- 12496512
TI  - The expanding spectrum of systemic autoinflammatory disorders and their rheumatic
      manifestations.
AB  - The authors review the genes, and their respective proteins, responsible for
      eight autoinflammatory conditions. Familial Mediterranean fever is caused by
      mutations in pyrin, which is the prototype of a new family of proteins belonging
      to the death-domain superfamily. This new group of proteins, which regulate
      apoptosis, inflammation, and cytokine processing, share an approximately 90-amino
      acid N-terminal sequence called the PYRIN domain. Mutations in another PYRIN
      domain protein, termed cryopyrin, are responsible for three clinically defined
      illnesses, Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and
      NOMID/CINCA. A related protein encoded by the gene is responsible for the
      Mendelian disorder, Blau syndrome, and also predisposes to Crohn disease. The
      gene responsible for PAPA syndrome has recently been identified as, and
      preliminary results from the authors' laboratory also implicate its protein
      product in these pathways. Lastly, the authors discuss the broadening genetic and
      clinical spectrum of TRAPS, an autoinflammatory syndrome resulting from mutations
      in the 55-kDa receptor for tumor necrosis factor.

PMID- 12496513
TI  - Musculoskeletal manifestations of benign and malignant tumors of bone.
AB  - Benign and malignant tumors of bone often have common musculoskeletal
      manifestations mimicking rheumatic disorders. The detection and resolution of
      mimicking symptoms require knowledge, skills, and a problem-solving attitude for
      musculoskeletal disorders. Before engaging in an extensive investigation, a
      careful history and full physical examination must be done. This review addresses
      the recent literature from June 2001 to May 2002 on musculoskeletal
      manifestations of benign and malignant tumors of bone using "red flag" rubrics:
      nonspecific pain pattern, atypical soft-tissue or bony swellings, pathologic
      fracture, spinal paresis, osteolytic x-ray findings, and unexpected results of
      laboratory tests. Early diagnosis (appropriate use of imaging techniques) and
      multidisciplinary management have improved considerably the survival of patients
      with primary malignant bone disease (eg, osteosarcoma). For some benign bone
      tumors (eg, osteoid osteoma), interstitial laser photocoagulation is now the
      treatment of choice with a success rate comparable with that of other treatments.

PMID- 12496514
TI  - Drug-induced rheumatic syndromes.
AB  - Rheumatic syndromes related to drug therapies have been described for decades.
      The introduction of many new therapeutic agents in recent years has been
      accompanied by an increase in such reported associations. By definition, drug
      induced syndromes are temporally related to starting a drug, and the symptoms and
      signs generally regress with its discontinuation. The classic and still most
      common cases resemble systemic lupus erythematosus or scleroderma. Some newer
      agents appear related to myositis or vasculitis. The origins of most of these
      syndromes remain obscure.

PMID- 12496515
TI  - Dedicated double breast coil for magnetic resonance mammography imaging, biopsy,
      and preoperative localization.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to compare the performance of
      a dedicated double breast coil for MR imaging and intervention with a standard
      diagnostic double breast coil. MATERIALS AND METHODS: Signal-to-noise ratios
      (SNRs) were determined for both coils by using a water phantom. Fourteen patients
      were examined, 11 underwent preoperative hookwire localization, two were
      biopsied, and one received diagnostic imaging. Breast images were acquired in
      three patients with both coils and were visually compared. Harvested specimen
      from the biopsies and surgeries following hookwire localization were
      histopathologically evaluated. RESULTS: SNR was superior with the interventional
      coil in the posterior (axillary) part of the imaging volume and inferior in the
      anterior part compared with the standard coil. Anatomic MR breast images were of
      similar diagnostic quality. For the two biopsy procedures the trocar was
      correctly placed in front of the suspicious lesion. Hookwires were correctly
      located inside the lesion in nine patients and in contact with the lesion in one
      patient. In one patient a 2 mm distance between the lesion and the wire was
      observed. CONCLUSIONS: Diagnostic imaging followed by subsequent MR-guided
      intervention is possible within a single session by using the dedicated
      interventional coil. The correct final position of the hookwires demonstrates the
      precision of the MR guided localization procedure.

PMID- 12496516
TI  - Low-dose multislice spiral computed tomography in acute lung injury: animal
      experience.
AB  - RATIONALE AND OBJECTIVES: To compare low-dose multislice spiral CT (MSCT) with a
      standard protocol for the evaluation of acute lung injury (ALI) in an animal
      model. MATERIALS AND METHODS: Eleven healthy intubated pigs (weight: 32.4 kg +/-
      1.9 kg) underwent lung lavage to induce experimental lung injury before CT
      examinations. Scanning was performed using a MSCT-technique. The entire chest was
      scanned using a thin-collimated protocol (140 kV; 100 mAs). The examinations were
      performed in inspiratory breath-hold in supine and in prone positions. Scanning
      was repeated after reduction of the tube current time product down to 20 mAs. All
      other parameters were kept constant. Subjective image quality was rated using a
      six-point scale by three experienced radiologists. In addition, objective
      criteria, based on signal to noise measurements, were assessed. Finally, the
      extent, localization, and distribution of lung opacities was analyzed using
      dedicated postprocessing software. RESULTS: Subjective image quality was rated
      inferior in the low-dose MSCT-examinations (prone position: 2.1 vs. 3.0; supine
      position: 1.5 vs. 2.5). Hence, pixel noise was nearly doubled. However, exact
      information about the extent, localization and distribution of lung opacities was
      provided. There were no statistically significant differences between standard
      and low-dose MSCT in this respect. CONCLUSIONS: In the animal experiments, low
      dose MSCT-scanning did not impair the diagnostic accuracy in ALI, offering an
      advantageous reduction of radiation exposure.

PMID- 12496517
TI  - Use of additives to contrast media to improve imaging in plain film and computed
      tomography urography.
AB  - RATIONALE AND OBJECTIVES: To investigate the effects of additives to iodinated
      radiograph contrast agents on image quality in plain film and CT urography.
      MATERIALS AND METHODS: Urea (52 mg/mL), iloprost (10, 20, 50, and 100 ng/mL),
      nifedipine (0.02 mg/mL), papaverine (0.625 mg/mL) and sodium nitroprusside (0.05
      microg/mL) were added to commercial iopromide (300 mg/mL) and iotrolan
      preparations (280 mg/mL) and plain film urograms were obtained at different time
      points after contrast injection in rabbits and dogs at iodine doses of 300 or 600
      mg/kg body weight. The experiments were repeated in rabbits using CT imaging and
      iopromide or iotrolan plus urea (52 mg/mL) or iloprost (20 ng/mL) and iodine
      doses of 50 mg/kg body weight. RESULTS: Urea and iloprost at low concentrations
      (10 and 20 ng/mL) increased image quality both in plain film and in CT urography.
      Iloprost at high concentrations (50 and 100 ng/mL), nifedipine, papaverine and
      sodium nitroprusside decreased image quality. An increase in image quality was
      accompanied by faster renal elimination of the contrast agent. CONCLUSION: Image
      quality in plain film and CT urography might be improved by additives to the
      contrast medium. More data, particularly on dose-response relationships are
      needed.

PMID- 12496518
TI  - Intraindividual comparison of gadopentetate dimeglumine, gadobenate dimeglumine,
      and gadobutrol for pelvic 3D magnetic resonance angiography.
AB  - RATIONALE AND OBJECTIVES: To compare the effect on image quality of a 1.0 mol/L
      gadolinium chelate with that of two 0.5 mol/L gadolinium compounds. MATERIALS AND
      METHODS: Five healthy volunteers underwent a mono-station 3D MRA exam (Siemens
      SONATA, Erlangen, Germany) four times using four separate gadolinium
      preparations. All subjects first received a fixed volume of undiluted gadobutrol
      (1 mol/L), which corresponded to a dose between 0.1 and 0.15 mmol/kg body weight.
      This gadobutrol dosage was then diluted with saline into twice the volume and
      administered as a bolus at twice the injection rate. For Gd-DTPA and Gd BOPTA,
      because these contrast agents are 0.5 mol/L preparations, the volume and flow
      rate were doubled to match diluted gadobutrol volume and concentration.
      Quantitative and qualitative analysis of the angiographic data sets was performed
      on nine arterial segments. RESULTS: Image quality was rated diagnostic for all
      image data sets without statistically significant differences between any of the
      compounds (P > 0.3). Quantitative measurements of Gd BOPTA (SNR: 81.15; CNR:
      68.91) and both standard and diluted forms of gadobutrol (SNR: 84.33; CNR: 71.62;
      SNR(diluted): 79,23; CNR(diluted): 66.26) yielded significantly higher results (P
      < 0.02) in comparison with Gd-DTPA (SNR: 49.55; CNR: 38.24). The difference
      between either form of gadobutrol and Gd BOPTA was not shown to be statistically
      significant (P > 0.3), whereas both the SNR and CNR of standard gadobutrol were
      significantly higher than diluted gadobutrol. CONCLUSION: Gadobutrol- and Gd
      BOPTA-MRA exams lead to improved delineation of the pelvic arterial morphology
      compared with MRA exams performed with Gd-DTPA.

PMID- 12496519
TI  - In vivo comparative antithrombotic effects of ioxaglate and iohexol and
      interaction with the platelet antiaggregant clopidogrel.
AB  - RATIONALE AND OBJECTIVES: Experiments were designed to (1) compare the effects of
      iodinated contrast media (CM) on a rat model of arterial thrombosis, (2) evaluate
      which element of the ioxaglate solution supports its antithrombotic activity, and
      (3) investigate the interaction of ionic and non-ionic CM with the antiplatelet
      agent clopidogrel. MATERIALS AND METHODS: Carotid thrombosis was induced in rats
      by extravascular application of a filter paper soaked in FeCl3 (35% vol/wt),
      proximal to an ultrasonic flow probe. (1) The antithrombotic potential of low
      osmolar ionic (ioxaglate Na/meglumine) or nonionic contrast media (iohexol and
      iodixanol) (all 1600 mg iodine/kg, IV) was assessed by measuring the time to
      occlusion (TTO) of the carotid artery and the thrombus weight (TW). (2) Isotonic
      saline and iso-osmolar (280 mOsm/kg) and hyperosmolar (560 mOsm/kg) solutions of
      meglumine hydrochloride, meglumine ioxaglate (560 mOsm/kg), sodium ioxaglate (600
      mOsm/kg) and sodium and meglumine ioxaglate (commercial solution) were tested
      under similar conditions. (3) Interaction with clopidogrel was tested by
      injecting lower dose of CM (960 mg iodine/kg) 2 hours after clopidogrel (2 mg/kg
      per os). RESULTS: (1) Ioxaglate prolonged TTO when compared with saline (30.0 +/-
      1.1 minute vs. 19.6 +/- 2.4 minutes, P< 0.001), whereas iohexol had no effect
      (21.3 +/- 1.3 minutes). Ioxaglate's effect was associated with a reduction in TW
      with ioxaglate versus saline (2.6 +/- 0.4 mg and 4.7 +/- 0.7 mg, respectively, P<
      0.05) whereas TW remained unchanged in the iohexol group (4.2 +/- 0.4 mg). The
      nonionic dimer iodixanol induced a direct vasoconstrictor effect on the carotid
      artery and was consequently excluded from the study. (2) Neither iso-osmolar nor
      hyperosmolar solutions of meglumine had any effect on TTO whereas both sodium and
      meglumine salts of ioxaglic acid prolonged TTO, suggesting that the
      antithrombotic effect of ioxaglate is mediated by the ioxaglic acid moiety alone
      as neither meglumine, osmolality or sodium played a significant role. (3) A
      synergistic effect on TTO was found when ioxaglate was associated with
      clopidogrel whereas no such effect was observed with iohexol. CONCLUSIONS: These
      data show a greater in vivo antithrombotic potential for the ionic contrast
      medium ioxaglate than for the non-ionic contrast medium iohexol and, for the
      first time, a synergistic effect between a contrast medium and a platelet
      antiaggregant drug in vivo.

PMID- 12496520
TI  - Comparison of open- and closed-chest canine model for quantification of coronary
      stenosis severity by myocardial contrast echocardiography.
AB  - RATIONALE AND OBJECTIVES: The objective of the present study was to compare the
      data regarding the ability of real-time myocardial contrast echocardiography
      (MCE) to assess altered myocardial blood flow produced by graded coronary
      stenoses between open- and closed-chest canine models. MATERIALS AND METHODS:
      Three grades of left anterior descending coronary artery stenosis and occlusion
      were created in 6 open- and 6 closed-chest canine models. MCE used FS-069
      infusion and real-time imaging. Myocardial signal intensity versus time plots
      were fitted to a 1-exponential function to obtain the peak signal intensity (A)
      and rate of signal intensity rise (b) for quantification of myocardial blood
      flow. RESULTS: The value of b obtained from closed-chest canine models (without
      stenosis = 0.995 +/- 0.087, mild stenosis = 0.968 +/- 0.076, moderate stenosis =
      0.569 +/- 0.077, severe stenosis = 0.288 +/- 0.032, occlusion = 0.085 +/- 0.031)
      was not significantly different from that obtained from open-chest canine models
      (without stenosis = 1.028 +/- 0.107, mild stenosis = 0.998 +/- 0.098, moderate
      stenosis = 0.601 +/- 0.055, severe stenosis = 0.321 +/- 0.029, occlusion = 0.079
      +/- 0.028) at any grade of stenosis (P = 0.09, 0.08, 0.44, 0.11, 0.74,
      respectively). CONCLUSIONS: In myocardial regions where attenuation of the
      ultrasound beam and artifacts produced by the chest wall are minimal, the data
      from transthoracic MCE in the closed-chest model may show values similar to those
      from MCE in the open-chest model.

PMID- 12496521
TI  - Posterior tibialis tendon tears: comparison of the diagnostic efficacy of
      magnetic resonance imaging and ultrasonography for the detection of surgically
      created longitudinal tears in cadavers.
AB  - RATIONALE AND OBJECTIVES: The optimal advanced imaging method for detection and
      characterization of posterior tibialis tendon (PTT) tears is unclear. The purpose
      of this study was to investigate the utility of ultrasonography (US) and MR
      imaging in the detection of surgically created PTT tears in cadavers. MATERIALS
      AND METHODS: This was a prospective blinded study in which 16 fresh cadaveric
      foot and ankle specimens (3 men, 13 women; average age at death 83.9 years; age
      range 71-96 years) were scanned with both US and MR imaging before and after the
      surgical creation of 64 variable length longitudinal tears of the PTT.
      Ultrasonography was performed with a 12 MHz linear transducer with independent
      interpretations of static and dynamic studies separately by two blinded and
      experienced musculoskeletal radiologists. MR imaging was performed at 1.5 T with
      a standard transmit-receive extremity coil using axial, sagittal, coronal T1
      weighted (TR 600, TE 20), and axial fast spin echo proton density and T2-weighted
      (TR 3000, TE 161/20, ETL 12) images. MR images were reviewed independently by two
      experienced musculoskeletal radiologists who were blinded to the status of the
      PTT. RESULTS: Sensitivity, specificity, and accuracy of MR imaging in the
      diagnosis of PTT tears were 73%, 69%, and 72%, respectively. Dynamic US
      interpretation yielded values of 69% sensitivity, 81% specificity, and 72%
      accuracy. Static US interpretation was less reliable than dynamic interpretation,
      and the only significance of static imaging was a high specificity (94%) for
      detection of longitudinal tears. The positive predictive value (PPV) for MR
      imaging and US was 88% and 92% respectively, and the negative predictive value
      (NPV) was 46% for both MR imaging and US. CONCLUSION: Our results suggest that US
      and MR imaging perform at the same level for the detection of surgically created
      longitudinal PTT tears in a cadaveric model. US has a higher specificity compared
      with MR imaging.

PMID- 12496522
TI  - Influence of monitor luminance change on observer performance for detection of
      abnormalities depicted on chest radiographs.
AB  - RATIONALE AND OBJECTIVES: To investigate how changes in luminance affect the
      detection accuracy of radiologists viewing chest radiograph images on high
      resolution CRT monitors. MATERIALS AND METHODS: Thirteen radiologists performed a
      detection task for 11 chest radiograph images with simulated nodules on a monitor
      with 11 luminance conditions (the maximum luminance ranges from 157.4-369.0
      candela/m2) simulating CRT degraded by long-term usage, under the ambient
      illumination of 200 lux; the observation order was always from the darkest to the
      brightest. RESULTS: There was a statistically reliable effect of the 11 monitor
      display conditions on the detection of nodules (P < 0.001). In the conditions in
      which the maximum luminance of the CRT was 60.7% or below that of the standard
      display luminance, the correctly detected nodule number reliably deteriorated.
      CONCLUSIONS: The luminance change in CRT monitor display under long-term usage
      will have a detrimental effect on nodule detection performance in chest
      radiograph images.

PMID- 12496523
TI  - Laparoscopic gastric banding: a minimally invasive surgical treatment for morbid
      obesity: prospective study of 500 consecutive patients.
AB  - OBJECTIVE: To evaluate early and late morbidity of laparoscopic adjustable
      gastric banding for morbid obesity and to assess the efficacy of this procedure
      by analyzing its results. SUMMARY BACKGROUND DATA: Laparoscopic adjustable
      gastric banding is considered the least invasive surgical option for morbid
      obesity. It is effective, with an average loss of 50% of excessive weight after 2
      years of follow-up. It is potentially reversible and safe; major morbidity is low
      and there is no mortality. METHODS: Between April 1997 and June 2001, 500
      patients underwent laparoscopic surgery for morbid obesity with application of an
      adjustable gastric band. There were 438 women and 62 men (sex ratio = 0.14) with
      a mean age of 40.4 years. Preoperative mean body weight was 120.7 kg and mean
      body mass index (BMI) was 44.3 kg. m. RESULTS: Mean operative time was 105
      minutes, 84 minutes during the last 300 operations. Mean hospital stay was 4.5
      days. There were no deaths. There were 12 conversions (2.4%), 2 during the last
      300 operations. Fifty-two patients (10.4%) had complications requiring an
      abdominal reoperation. Forty-nine underwent a reoperation for minor
      complications: slippage (n = 43, incisional hernias (n = 3), and reconnection of
      the catheter (n = 3). Three patients underwent a reoperation for major
      complications: gastroesophageal perforation (n = 2) and gastric necrosis (n = 1).
      Seven patients had pulmonary complications and 36 patients experienced minor
      problems related to the access port. At 1-, 2-, and 3-year follow-up, mean BMI
      decreased from 44.3 kg. m to 34.2, 32.8, and 31.9, respectively, and mean excess
      weight loss reached 42.8%, 52%, and 54.8%. CONCLUSIONS: Laparoscopic adjustable
      gastric banding is a beneficial operation in terms of excessive weight loss, with
      an acceptably low complication rate. It can noticeably improve the quality of
      life in obese patients. Half of the excess body weight can be effortlessly lost
      within 2 years.

PMID- 12496524
TI  - Surgical treatment of severe obesity with a low-pressure adjustable gastric band:
      experimental data and clinical results in 625 patients.
AB  - OBJECTIVE: To evaluate the use of a low-pressure gastric band in the treatment of
      severe obesity in a prospective study. SUMMARY BACKGROUND DATA: Gastric banding
      for severe obesity has been associated with erosion and perforation of the
      stomach. The Swedish adjustable gastric band (SAGB) has been proposed as a low
      pressure device. METHODS: From January 1998 to October 2001, 625 patients
      underwent laparoscopic SAGB. Median age was 36 years, and 80.4% of patients were
      female. Median preoperative body mass index (BMI) was 40. Previous upper
      abdominal surgery was reported in 36 (6%) patients. A five-trocar technique was
      used without a calibration balloon. RESULTS: Median follow-up was 19.5 months.
      All patients were treated laparoscopically with a median operating time of 80
      minutes. Conversion was necessary in two patients (0.3%): one trocar injury of
      the mesentery and one esophageal perforation. Median hospital stay was 3 days;
      there were no 30-day deaths. Early morbidity was present in 27 patients (4.3%).
      Late band reoperation was necessary in 49 patients (7.8%). Indications for
      reoperation were band slippage or pouch dilation, acute total dysphagia, and band
      leakage or malfunction. Median excess weight loss was 45.8%, 49.9%, and 47.4%
      after 1, 2, and 3 years, respectively, with a measurable beneficial effect on
      arterial hypertension, sleep apnea syndrome, and diabetes control. CONCLUSIONS:
      SAGB is a safe and effective new method in the management of severe obesity. Long
      term follow-up (>3 years) is necessary to confirm its effectiveness and safety.

PMID- 12496525
TI  - Gastric banding.

PMID- 12496526
TI  - Composite tissue allotransplantation and reconstructive surgery: first clinical
      applications.
AB  - OBJECTIVE: To review the first clinical cases of composite tissue
      allotransplantation (CTA) for reconstructive surgery and to discuss the outcome
      of and indications for these procedures in the context of chronic
      immunosuppression. SUMMARY BACKGROUND DATA: The first human hand transplant was
      performed in 1998. This procedure, as well as other composite tissue transplants,
      offers the potential for correcting untreatable large tissue defects. However,
      concerns remain regarding obligatory chronic immunosuppression and long-term
      functional results. METHODS: All the CTAs performed in humans that have been
      published or documented were reviewed. The preexisting clinical conditions and
      surgical procedures and the immunosuppressive therapy are described. The
      functional results and the complications or side effects of the treatment are
      detailed. RESULTS: Vascularized tendons (two cases), vascularized femoral
      diaphyses (three cases), knees (five cases), hands (four bilateral and seven
      unilateral cases), larynx (one case), and nonvascularized peripheral nerves
      (seven cases) have been transplanted in humans in the past decade. Rejection was
      prevented in most cases without difficulty. Early results are encouraging,
      particularly for hand and larynx transplants, but will need to be evaluated in
      the long term and in a larger number of patients. CONCLUSIONS: CTA holds great
      potential for reconstructive surgery but is at present restricted by the risks of
      chronic immunosuppression and uncertain long-term results.

PMID- 12496527
TI  - Oncoplastic techniques allow extensive resections for breast-conserving therapy
      of breast carcinomas.
AB  - OBJECTIVE: To assess the oncologic and cosmetic outcomes in women with breast
      carcinoma who were treated with breast-conserving therapy using oncoplastic
      techniques with concomitant symmetrization of the contralateral breast. SUMMARY
      BACKGROUND DATA: Although breast-conserving therapy is the standard form of
      treatment for invasive breast tumors up to 4 cm, in patients with large, ill
      defined, or poorly situated tumors, cosmetic results can be poor and clear
      resection margins difficult to obtain. The integration of oncoplastic techniques
      with a concomitant contralateral symmetrization procedure is a novel surgical
      approach that allows wide excisions and prevents breast deformities. METHODS:
      This is a prospective study of 101 patients who were operated on for breast
      carcinoma between July 1985 and June 1999 at the Institut Curie. The procedure
      was proposed for patients in whom conservative treatment was possible on
      oncologic grounds but where a standard lumpectomy would have led to poor
      cosmesis. Standard institutional treatment protocols were followed. All patients
      received either pre- or postoperative radiotherapy. Seventeen patients received
      preoperative chemotherapy to downsize their tumors. Mean follow-up was 3.8 years.
      Results were analyzed statistically using Kaplan-Meier estimates. RESULTS: Mean
      weight of excised material on the tumor side was 222 g. The actuarial 5-year
      local recurrence rate was 9.4%, the overall survival rate was 95.7%, and the
      metastasis-free survival rate was 82.8%. Cosmesis was favorable in 82% of cases.
      Preoperative radiotherapy resulted in worse cosmesis than when given
      postoperatively. CONCLUSIONS: The use of oncoplastic techniques and concomitant
      symmetrization of the contralateral breast allows extensive resections for
      conservative treatment of breast carcinoma and results in favorable oncologic and
      esthetic outcomes. This approach might be useful in extending the indications for
      conservative therapy.

PMID- 12496528
TI  - Immune responses and prediction of major infection in patients undergoing
      transhiatal or transthoracic esophagectomy for cancer.
AB  - OBJECTIVE: To investigate alterations in immune responses after transhiatal
      versus transthoracic esophageal resection and to evaluate the role of
      preoperative immune functions in predicting postoperative infectious
      complications. SUMMARY BACKGROUND DATA: Impaired immune defense is associated
      with a decreased resistance to infection. Patients undergoing esophageal
      resection via a transhiatal or transthoracic approach are prone to develop
      infectious complications. There are no randomized data on immune responses after
      two major surgical interventions. METHODS: The study group consisted of 20
      patients who were randomly allocated to a limited transhiatal or extended
      transthoracic esophagectomy for cancer. Blood samples were taken before the
      operation and at regular intervals thereafter from day 1 to day 10. Monocyte and
      T-helper type 1 (Th1) and type 2 (Th2) lymphocyte functions were assessed in
      stimulated whole blood cultures. RESULTS: Both surgical groups had severely
      depressed in vitro production of interleukin (IL)-12, IL-10, interferon-gamma, IL
      2, IL-4, and IL-13 on postoperative day 1. Depression of Th2-type cytokine
      production was more profound after transthoracic than after transhiatal
      esophagectomy (IL-4, P=.005; IL-13,P=.007). Postoperative reduction in Th1-type
      cytokine production was similar between the two groups (interferon-gamma, P=.40;
      IL-2, P=.06). Irrespective of the surgical approach, patients who developed major
      infectious complications after surgery presented with a diminished T-cell
      cytokine production before the operation compared to those who had a relatively
      uneventful recovery (IL-4, P=.045; interferon-gamma, P=.064). In regression
      analysis, the occurrence of postoperative major infection was best predicted by
      increased duration of anesthesia ( P<.0001) and low preoperative interferon-gamma
      production ( P=.006). CONCLUSIONS: Both transhiatal and transthoracic
      esophagectomy induced severely depressed monocyte and T-lymphocyte cytokine
      production. The extent of the surgical procedure had a differential
      immunosuppressive impact on Th2-type but not on Th1-type cell activity,
      indicating that the two Th pathways were downregulated through distinct
      mechanisms. Preoperative interferon-gamma determination would be useful to
      anticipate the occurrence of postoperative major infectious complications.

PMID- 12496529
TI  - Effect of prolonged hyperdynamic endotoxemia on jejunal motility in fasted and
      enterally fed pigs.
AB  - OBJECTIVE: To determine the effects of hyperdynamic endotoxemia on the motility
      of the small intestine. SUMMARY BACKGROUND DATA: Motility disorders of the
      gastrointestinal tract are a common complication of sepsis. It has been suggested
      that gram-negative endotoxin plays a role in the pathogenesis of the accompanying
      diarrhea frequently observed. METHODS: Pigs were infused with lipopolysaccharide
      for a 24-hour period. During this fasting period jejunal motility was measured
      using ambulatory manometry. One and 4 days after cessation of endotoxin, pigs
      were enterally fed, and again motility was recorded. RESULTS: Hyperdynamic
      endotoxemia was achieved in this model. Manometric pressure recordings revealed
      that endotoxin infusion accelerated the migrating motor complex (MMC) migration
      along the jejunum. Also, a simultaneous increase in MMC cycling frequency was
      observed in the endotoxin-treated group. Elevated MMC migration velocity and
      cycling frequency were maintained the following day after endotoxin during
      feeding and returned to basal values 4 days after endotoxin. CONCLUSIONS: A small
      dose of continuously infused endotoxin significantly provokes jejunal motility
      disturbances that may contribute to diarrhea.

PMID- 12496530
TI  - Artificial anal sphincter in severe fecal incontinence: outcome of prospective
      experience with 37 patients in one institution.
AB  - OBJECTIVE: To evaluate the outcome of artificial anal sphincter implantation for
      severe fecal incontinence in 37 consecutive patients operated on in a single
      institution from 1993 through 2001. SUMMARY BACKGROUND DATA: Implantation of an
      artificial anal sphincter is proposed in severe fecal incontinence when local
      treatment is unsuitable or has failed. The results of this technique have not
      been determined yet, and its place among the various operative procedures is
      still debated. METHODS: Artificial anal sphincters were implanted in 37 patients
      from 1993 through 2001. All patients had complete fecal incontinence and had
      failed to respond to medical treatment. Median duration of incontinence was 16
      years. The causes of incontinence were sphincter disruption (19 patients),
      hereditary malformations (2 patients), and neurologic disease (16 patients). Six
      patients had had previous surgery for fecal incontinence. Assessment was made by
      physical examination (anal continence, rectal emptying) and anorectal manometry.
      RESULTS: In the first 12 patients, six devices had to be removed (50%); the cause
      of failure was found in all cases, and this allowed contraindications to be
      defined. Among the next 25 patients, 23 had an uncomplicated postoperative follow
      up, and 5 developed seven complications: control pump change (n = 3), balloon
      migration (n = 1), and major rectal emptying difficulties in patients with
      obstructive internal rectal procidentia (n = 2). The artificial anal sphincter
      had to be removed definitively in three cases, representing the failure rate of
      this technique in the authors' experience (12%); two other devices had to be
      removed temporarily and the patients are awaiting reimplantation. In this latter
      group of 25 patients, 80% have an activated sphincter: continence for liquid
      stool is normal in 78.9%, continence for gas in 63.1%. Seven patients have rectal
      emptying difficulties, minor in five and major in two. Manometric studies showed
      mean pressures of 110 and 37 cm H(2)O with closed and open sphincter,
      respectively, with a mean duration of artificial sphincter opening of 128
      seconds. CONCLUSIONS: The long-term functional outcome of artificial anal
      sphincter implantation for severe fecal incontinence is satisfactory; adequate
      sphincter function is recovered and the definitive removal rate is low. Good
      results are directly related to careful patient selection and appropriate
      surgical and perioperative management after a learning curve of the surgical
      team.

PMID- 12496531
TI  - Temporary fibrin glue occlusion of the main pancreatic duct in the prevention of
      intra-abdominal complications after pancreatic resection: prospective randomized
      trial.
AB  - OBJECTIVE: To determine whether temporary occlusion of the main pancreatic duct
      with human fibrin glue decreases the incidence of intra-abdominal complications
      after pancreatoduodenectomy (PD) or distal pancreatectomy (DP). SUMMARY
      BACKGROUND DATA: To the authors' knowledge, there are no randomized studies
      comparing outcomes after pancreatic resection with or without main pancreatic
      duct occlusion by injection of fibrin glue. Of three nonrandomized studies, two
      reported no fistulas after intracanal injection and ductal occlusion with fibrin
      glue after PD with immediate pancreatodigestive anastomosis, while another study
      reported no protective effect of glue injection. METHODS: This prospective,
      randomized, single-blinded, multicenter study, conducted between January 1995 and
      January 1999, included 182 consecutive patients undergoing PD followed by
      immediate pancreatic anastomosis or DP, whether for benign or malignant tumor or
      for chronic pancreatitis. One hundred two underwent pancreatic resection followed
      by ductal occlusion with fibrin glue (made slowly resorbable by the addition of
      aprotinin); 80 underwent resection without ductal occlusion. The main end point
      was the number of patients with one or more of the following intra-abdominal
      complications: pancreatic or other digestive tract fistula, intra-abdominal
      collections (infected or not), acute pancreatitis, or intra-abdominal or
      digestive tract hemorrhage. Severity factors included postoperative mortality,
      repeat operations, and length of hospital stay. RESULTS: The two groups were
      similar in pre- and intraoperative characteristics except that there were
      significantly more patients in the ductal occlusion group who were receiving
      octreotide, who had reinforcement of their anastomosis by fibrin glue, and who
      had fibrotic pancreatic stumps. However, the rate of patients with one or more
      intra-abdominal complications, and notably with pancreatic fistula, did not
      differ significantly between the two groups. There was still no significant
      difference found after statistical adjustment for these patient characteristic
      discrepancies, confirming the inefficacy of fibrin glue. The rate of intra
      abdominal complications was significantly higher in the presence of a normal,
      nonfibrotic pancreatic stump and main pancreatic duct diameter less than 3 mm,
      whereas reinforcement of the anastomosis with fibrin glue or use of octreotide
      did not influence outcome. In multivariate analysis, however, normal pancreatic
      parenchyma was the only independent risk factor for intra-abdominal
      complications. No significant differences were found in the severity of
      complications between the two groups. CONCLUSIONS: Ductal occlusion by intracanal
      injection of fibrin glue decreases neither the rate nor the severity of intra
      abdominal complications after pancreatic resection.

PMID- 12496532
TI  - Laparoscopic staging and subsequent palliation in patients with peripancreatic
      carcinoma.
AB  - OBJECTIVE: To test the hypothesis that laparoscopic staging improves outcome in
      patients with peripancreatic carcinoma compared to standard radiology staging.
      SUMMARY BACKGROUND DATA: Diagnostic laparoscopy of peripancreatic malignancies
      has been reported to improve assessment of tumor stage and to prevent unnecessary
      exploratory laparotomies in 10% to 76% of patients. METHODS: Laparoscopy and
      laparoscopic ultrasound were performed in 297 consecutive patients with
      peripancreatic carcinoma scheduled for surgery after radiologic staging. Patients
      with pathology-proven unresectable tumors were randomly allocated to either
      surgical or endoscopic palliation. All others underwent laparotomy. RESULTS:
      Laparoscopic staging detected biopsy-proven unresectable disease in 39 patients
      (13%). At laparotomy, unresectable disease was found in another 72 patients,
      leading to a detection rate for laparoscopic staging of 35%. In total, 145 of the
      197 patients classified as having "possibly resectable" disease after
      laparoscopic staging underwent resection (74%). Average survival in the group of
      14 patients with biopsy-proven unresectable tumors randomly allocated to
      endoscopic palliation was 116 days, with a mean hospital-free survival of 94
      days. The corresponding figures were 192 days and 164 days in the 13 patients
      allocated to surgical palliation. CONCLUSIONS: Because of the limited detection
      rate for unresectable metastatic disease and the likely absence of a large gain
      after switching from surgical to endoscopic palliation, laparoscopic staging
      should not be performed routinely in patients with peripancreatic carcinoma.

PMID- 12496533
TI  - Prognostic factors following curative resection for pancreatic adenocarcinoma: a
      population-based, linked database analysis of 396 patients.
AB  - OBJECTIVE: To analyze prognostic factors influencing pancreatic cancer survival
      following curative resection, using prospectively collected, population-based
      data. SUMMARY BACKGROUND DATA: Several studies have analyzed the determinants of
      long-term survival in postresection pancreatic cancer patients, but the majority
      of these have been single-institutional chart reviews yielding inconsistent
      results. METHODS: This retrospective cohort study examined 396 Medicare-eligible
      patients over age 65 who were diagnosed with nonmetastatic pancreatic
      adenocarcinoma and who underwent surgical resection with curative intent while
      residing in one of the 11 Survival, Epidemiology, and End Results (SEER)
      registries between January 1991 and December 1996. Linked Medicare data provided
      information on treatment and comorbidity, while linked census tract data supplied
      sociodemographic characteristics. RESULTS: Median survival for the overall study
      population was 17.6 months, with 1- and 3-year survival rates of 60.1% and 34.3%,
      respectively. Survival appears to be gradually improving over time, concomitant
      with a rise in the proportion of patients undergoing surgery in teaching centers.
      Prognostic variables significantly diminishing survival on univariate analysis
      included African American race, treatment not in a teaching hospital, lack of
      adjuvant chemoradiation therapy, as well as histopathologic factors that included
      tumor size larger than 2 cm in diameter, moderate to poor histologic grade, and
      positive lymph node metastases. Higher socioeconomic status was associated both
      with an increased likelihood of receiving adjuvant therapy and improved overall
      survival. Multivariate analyses indicated the strongest predictors of survival
      were adjuvant combined chemoradiotherapy, small tumors (<2 cm in diameter),
      negative lymph nodes, well-differentiated histology, undergoing surgery in a
      teaching hospital, and high socioeconomic status. CONCLUSIONS: Although biologic
      characteristics remain important predictors of survival for patients with
      resected pancreatic cancer, the most powerful determinant is postoperative
      adjuvant chemoradiation therapy. An interesting finding that warrants further
      investigation is the effect of socioeconomic status on both the likelihood of
      receiving adjuvant treatment and subsequent survival, indicating a possible
      relationship between the quality of care delivered and outcomes.

PMID- 12496534
TI  - Cohort study of surgical bypass to the gallbladder or bile duct for the
      palliation of jaundice due to pancreatic cancer.
AB  - OBJECTIVE: To compare patterns in mortality and the use of subsequent biliary
      drainage interventions (surgical, endoscopic, and percutaneous) associated with
      the different types of biliary bypass. SUMMARY BACKGROUND DATA: Surgical
      palliation of obstructive jaundice due to pancreatic cancer is often accomplished
      with an intestinal bypass to either the gallbladder or the bile duct. It is not
      known whether a gallbladder bypass, which is a simpler operation and more
      amenable to laparoscopic surgery, performs as well as a bypass to the bile duct.
      METHODS: The authors conducted a retrospective cohort study of 1,919 patients 65
      years of age or older who had a surgical biliary bypass for pancreatic cancer
      diagnosed between 1991 and 1996 using Medicare claims data and the Surveillance,
      Epidemiology and End Results (SEER) database. RESULTS: At 1, 2, and 5 years,
      7.5%, 17.4%, and 26.0% of 945 patients initially treated with a gallbladder
      bypass had additional biliary interventions, as compared with 2.9%, 11.0%, and
      13.3% of 974 patients initially treated with a bile duct bypass. Patients who
      initially had a gallbladder bypass were 4.4 times as likely to have additional
      biliary surgery and 2.9 times as likely to have any subsequent biliary
      intervention as were patients who initially had a bile duct bypass. Median
      survival was longer following bile duct bypass. The adjusted hazard ratio for
      death associated with gallbladder bypass was 1.2. CONCLUSIONS: Compared to
      patients whose initial biliary bypass was to the bile duct, the risk of having
      one or more additional surgical, endoscopic, or percutaneous biliary drainage
      procedures is substantially greater in patients whose initial bypass was to the
      gallbladder.

PMID- 12496535
TI  - Mitogen-activated protein kinases in the intensive care unit: prognostic
      potential.
AB  - OBJECTIVE: To evaluate the prognostic significance of the activational status of
      p38, specifically progression to multiple organ dysfunction syndrome (MODS), in a
      group of severely injured trauma patients. SUMMARY BACKGROUND DATA: To date,
      therapeutic manipulation of the host immunoinflammatory response has not affected
      the outcome of patients with MODS. A major concern is the inability to identify
      the patient most at risk so as to enable early intervention. METHODS: Nineteen
      trauma patients underwent bronchoalveolar lavage (BAL). Cells obtained were
      plated, stimulated with lipopolysaccharide (LPS), and then harvested at varying
      time points after stimulation. p38 was evaluated by Western blot. RESULTS:
      Nineteen patients were categorized into two groups according to baseline and LPS
      stimulated p38 activation in cells obtained by BAL. Group 1 demonstrated a 10
      fold increase in p38 activation with LPS treatment over unstimulated controls.
      Group 2 had high baseline levels of p38 that were unresponsive to subsequent LPS
      stimulation. Both groups were similar with respect to age, gender, shock
      (systolic blood pressure < 90), Injury Severity Score, APACHE II, lactate levels,
      base deficit, blood transfusions, and the cell differential of BAL fluid.
      However, patients in group 2 had a greater incidence of progression to MODS as
      defined by the Marshall MOD score, a longer duration of mechanical ventilation, a
      longer stay in the intensive care unit, and a longer overall hospital stay than
      group 1. CONCLUSIONS: These results demonstrate the prognostic significance of
      p38 activation in predicting outcome in critically ill trauma patients.
      Furthermore, these results demonstrate that trauma populations identical by
      current scoring systems contain a mixture of patients with markedly different
      outcomes as identified by p38 activation. Measurement of p38 may enable early
      identification of a subgroup of patients at increased risk for MODS to permit
      effective therapeutic intervention.

PMID- 12496536
TI  - Effects of interleukin-1alpha administration on intestinal ischemia and
      reperfusion injury, mucosal permeability, and bacterial translocation in burn and
      sepsis.
AB  - OBJECTIVE: To evaluate the effect of interleukin-1alpha (IL-1alpha) on the
      mesenteric circulation, intestinal mucosal integrity, and bacterial translocation
      in a burn/endotoxemia chronic porcine model. SUMMARY BACKGROUND DATA: Major burn
      and sepsis are associated with a high mortality, ischemia/reperfusion injury to
      the intestine, and an increased rate of bacterial translocation. Pathologic
      alterations of IL-1 synthesis, degradation, and binding to receptors have been
      reported. Manipulation of IL-1-mediated effects might be of therapeutic utility.
      METHODS: Twenty-one female pigs were instrumented with an ultrasonic flow probe
      on the superior mesenteric artery and a catheter into the superior mesenteric
      vein. After 5 days, all animals were anesthetized, and 14 received 40% total body
      surface area third-degree burn. IL-1alpha was administered intravenously at 1,000
      ng/kg to seven pigs immediately after burn. Eighteen hours after burn, 100
      microg/kg lipopolysaccharide (LPS) was administered intravenously. Systemic and
      splanchnic hemodynamics were measured and blood samples were drawn for blood gas
      analysis. Intestinal permeability was assessed every 6 hours by measuring the
      lactulose/mannitol (L/M) excretion ratio. At the end of the study (42 hours),
      tissue samples were harvested for bacteriologic cultures. RESULTS: Mesenteric
      blood flow was significantly decreased after burn and endotoxin. Administration
      of IL-1alpha significantly improved mesenteric blood flow postburn and post-LPS.
      Mesenteric oxygen supply and consumption showed a significant reduction after
      burn. In contrast, animals treated with IL-1alpha showed an increase in postburn
      mesenteric oxygen supply and consumption. LPS-induced mesenteric hypoxia was also
      ameliorated by IL-1alpha treatment. Intestinal permeability, as assessed by the
      L/M ratio, showed a 7- and 10-fold elevation after thermal injury and LPS,
      respectively. In contrast, IL-1alpha-treated animals showed an increase of only
      three- and fourfold in the L/M ratio, respectively. Bacterial translocation was
      significantly increased in the burn/endotoxin group. IL-1alpha significantly
      reduced the rates of bacterial translocation. CONCLUSIONS: IL-1alpha treatment
      attenuates mesenteric ischemia and reperfusion injury induced by thermal injury
      and endotoxemia by improving mesenteric blood flow and oxygenation. Subsequently,
      IL-1alpha reduces intestinal permeability and bacterial translocation after burn
      and sepsis.

PMID- 12496537
TI  - Perioperative GLY-GLN infusion diminishes the surgery-induced period of
      immunosuppression: accelerated restoration of the lipopolysaccharide-stimulated
      tumor necrosis factor-alpha response.
AB  - OBJECTIVE: To investigate whether the administration of different glutamine
      containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has
      a differing impact on perioperative immunomodulation. SUMMARY BACKGROUND DATA:
      Surgery leads to transitory immunosuppression, which is associated with decreased
      plasma glutamine (GLN) levels and increased susceptibility to infection and
      sepsis. A useful tool to detect immunocompetence is the ex vivo
      lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha)
      secretion in whole blood. METHODS: Forty-five patients undergoing major abdominal
      surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides
      administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino
      acid solution; control group) as a continuous infusion over 72 hours, starting 24
      hours before surgery. Blood samples were collected before infusion, at the end of
      surgery, and 48 hours postoperatively to determine the TNF-alpha release into
      whole blood stimulated with LPS. Groups were compared by analysis of variance.
      RESULTS: The groups were comparable in age, gender distribution, and length of
      operative time. At the end of surgery a significant reduction in ex vivo LPS
      stimulated TNF-alpha production was observed in all groups. In patients who
      received GLY-GLN, the induced TNF-alpha production was restored after 48 hours.
      CONCLUSIONS: In this study perioperative infusion of GLY-GLN reduced
      immunosuppression. The effect of GLN-containing dipeptides seems to be different
      when administered in glycine or alanine form.

PMID- 12496538
TI  - Surgical repair of transplant renal artery stenosis with preserved cadaveric
      iliac artery grafts.
AB  - OBJECTIVE: To review the authors' experience with ABO-matched, preserved,
      cadaveric, iliac artery grafts for treatment of transplant renal artery stenosis
      (TRAS). SUMMARY BACKGROUND DATA: TRAS is an important and treatable cause of
      hypertension and graft dysfunction in renal allograft recipients. Surgical
      treatment is reserved for lesions that are not amenable to percutaneous
      transluminal angioplasty (PTA) or for recurrence after PTA. Various surgical
      options for reconstruction of the transplant renal artery exist, although no
      single technique has been demonstrated to be superior. The authors have used
      preserved, blood type-matched, iliac artery grafts procured from cadaver organ
      donors to reconstruct transplant renal arteries in patients with specific lesions
      and following unsuccessful PTAs. METHODS: Between 1991 and 2001, 21 patients
      underwent reconstruction of allograft renal arteries using cadaveric iliac artery
      as conduit. Charts, operative notes, and imaging studies of all patients were
      reviewed. A successful intervention for TRAS was defined as technical success as
      well as a decrease in serum creatinine and/or blood pressure 6 weeks after the
      procedure. Development of a hemodynamically significant lesion following renal
      artery reconstruction was considered a recurrence. RESULTS: In patients treated
      with surgical reconstruction, hemodynamically significant TRAS occurred at or
      within 1 to 2 mm of the anastomosis in 13 patients, in the middle of the renal
      artery in 4, and secondary to a kink in 2 patients. Surgical treatment was
      undertaken in seven patients following unsuccessful PTA. Two patients had
      aneurysms of the iliac artery. Reconstruction using cadaveric iliac artery was
      successful in 19 of 21 (90%) patients, and only 1 these patients (4.8%) failed
      due to recurrence, with a median follow-up of 42 months. Graft loss secondary to
      TRAS occurred in two patients. The authors have not seen any long-term
      complications related to cadaveric iliac artery grafts, and the majority of the
      allografts continue to function well. CONCLUSIONS: Surgical reconstruction of the
      transplant renal artery with blood type-matched iliac artery grafts should be
      considered a viable option for patients with specific anatomic lesions, those who
      have had an unsuccessful PTA, and those with recurrence following PTA.

PMID- 12496539
TI  - Prevention of adhesion to prosthetic mesh: comparison of different barriers using
      an incisional hernia model.
AB  - OBJECTIVE: To assess whether use of antiadhesive liquids or coatings could
      prevent adhesion formation to prosthetic mesh. SUMMARY BACKGROUND DATA:
      Incisional hernia repair frequently involves the use of prosthetic mesh. However,
      concern exists about development of adhesions between viscera and the mesh,
      predisposing to intestinal obstruction or enterocutaneous fistulas. METHODS: In
      91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed
      intraperitoneally to cover the defect. Rats were divided in five groups:
      polypropylene mesh only (control group), addition of Sepracoat or Icodextrin
      solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm
      coating), and Parietex composite mesh (polyester mesh with collagen coating).
      Seven and 30 days postoperatively, adhesions were assessed and wound healing was
      studied by microscopy. RESULTS: Intraperitoneal placement of polypropylene mesh
      was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of
      the mesh surface was covered by adhesions after 7 days, and 48% after 30 days.
      Administration of Sepracoat or Icodextrin solution had no influence on adhesion
      formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel
      adhesions. Sepramesh was associated with a significant reduction of the mesh
      surface covered by adhesions after 7 and 30 days. Infection was more prevalent
      with Parietex composite mesh, with concurrent increased mesh surface covered by
      adhesions after 30 days (78%). CONCLUSIONS: Sepramesh significantly reduced mesh
      surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex
      composite mesh prevented bowel adhesions as well but increased infection rates in
      the current model.

PMID- 12496540
TI  - Have outcomes of incisional hernia repair improved with time? A population-based
      analysis.
AB  - OBJECTIVE: To determine if certain outcomes of incisional hernia repair have
      improved in recent eras. SUMMARY BACKGROUND DATA: Technological developments have
      been reported to improve outcomes in the repair of abdominal wall incisional
      hernias. METHODS: This retrospective, population-based cohort study was conducted
      using a 1987 to 1999 Washington hospital discharge database. Subjects were all
      Washington state residents assigned ICD9 procedure codes for incisional hernia
      repair with or without synthetic material (mesh). Main outcome measure was the
      rate of reoperative incisional hernia repair, length of hospitalization, and
      hospital charges based on the use of synthetic material and the era of operative
      repair (before and after 1995). RESULTS: A total of 10,822 Washington state
      patients underwent incisional hernia repair (mean age 58.7 +/- 15.6, 64% female).
      Of patients undergoing incisional hernia repair, 12.3% underwent at least one
      subsequent reoperative incisional hernia repair within the first 5 years after
      initial repair (23.1% at 13 years follow-up). The 5-year reoperative rate was
      23.8% after the first reoperation, 35.3% after the second, and 38.7% after the
      third. The use of synthetic mesh in incisional hernia repairs increased from
      34.2% in 1987 to 65.5% in 1999. When controlling for age, sex, comorbidity index
      of the patient, year of the initial procedure, and hospital descriptors (rural
      location, nonprofit and teaching status), the hazard for recurrence was 24.1%
      higher if no mesh was used compared to the hazard if mesh was used. After similar
      adjustment, no differences were found in the hazard of reoperation based on the
      era of the operative repair. Mean length of stay for procedures performed after
      1995 was 4.9 days compared to 4.8 days in preceding eras. CONCLUSIONS: Incisional
      hernia repair is associated with high cumulative rates of reoperative repairs.
      The expectation that important measures of adverse outcome have improved in
      recent eras is not supported by the results of this large population-based study.

PMID- 12496541
TI  - Recurrences after conventional anterior and laparoscopic inguinal hernia repair:
      a randomized comparison.
AB  - OBJECTIVE: To study the long-term recurrence rate and other complications after
      conventional and laparoscopic inguinal hernia repair. SUMMARY BACKGROUND DATA:
      Reliable long-term follow-up of patients with inguinal hernias treated by
      laparoscopic repair techniques is lacking. METHODS: The authors performed a
      randomized, multicenter trial in which 487 patients with inguinal hernia were
      treated by totally extraperitoneal laparoscopic repair and 507 patients were
      treated by conventional anterior hernia repair. Patients were followed and
      examined for recurrence and chronic inguinal pain 2, 3, and 5 years after
      surgery. Risk factors for recurrence and chronic inguinal pain were assessed.
      RESULTS: Patients who underwent conventional repair had a high risk for
      recurrence compared to patients who underwent laparoscopic repair. Risk factors
      for recurrence were operative time and type of conventional repair. Predictive
      independent risk factors for chronic inguinal pain were conventional repair
      (Bassini repairs and non-bassini repairs), inguinal pain before surgery, and
      perioperative lesion of the ilioinguinal nerve. CONCLUSIONS: Patients with
      inguinal hernia who undergo laparoscopic repair have fewer recurrences and less
      chronic inguinal pain than those who undergo conventional open repair. The
      Bassini repair produces unacceptably high recurrence rates.

PMID- 12496542
TI  - Tension-free inguinal hernia repair: TEP versus mesh-plug versus Lichtenstein: a
      prospective randomized controlled trial.
AB  - OBJECTIVE: To compare laparoscopic hernioplasty with two open tension-free hernia
      repairs. SUMMARY BACKGROUND DATA: Laparoscopic hernioplasty is associated with a
      short rehabilitation, but it is a technically difficult procedure. It is unclear
      if it has advantages over the technically easier open tension-free herniorrhaphy.
      METHODS: Two hundred ninety-nine men 30 to 75 years old were randomized to
      undergo laparoscopic totally extraperitoneal hernioplasty (TEP), open operation
      with mesh-plug and patch, or Lichtenstein's operation. RESULTS: Two hundred
      ninety-four (98%) patients were followed for 19.8 +/- 8.6 months. Over 90% of the
      patients in all groups were operated in day surgery; the rest of the patients
      were all discharged within 24 hours. Postoperative pain (visual analog score) was
      lower in the patients undergoing TEP than in those undergoing Lichtenstein and
      mesh-plug procedures. The median sick-leave period was 5 days in the TEP group, 7
      days in the mesh-plug group, and 7 days in the Lichtenstein group. The median
      time to full recovery was significantly shorter in the TEP group compared to the
      other two groups. There were no major complications. Two recurrences were found
      in the TEP group and two in the mesh-plug group. CONCLUSIONS: Laparoscopic
      hernioplasty is superior to tension-free open herniorrhaphy in terms of
      postoperative pain and rehabilitation.

PMID- 12496543
TI  - Expectations of patients with gastroesophageal reflux disease for the outcome of
      laparoscopic antireflux surgery.
AB  - Goals of gastroesophageal reflux disease (GERD) treatment are symptom relief,
      healing of esophagitis, prevention of complications, and prevention of relapses.
      The aims of the current study were to evaluate a selected group of patients
      referred to our Department of General Surgery for presurgical examination (N =
      70: 41 males and 29 females) for their expectations about laparoscopic antireflux
      surgery and to compare these expectations with the official medical treatment
      goals. The leading expectations for laparoscopic antireflux surgery were as
      follows: (1) for 92.8%, abatement of GERD-related symptoms, especially heartburn,
      regurgitation, and pain; (2) for 84.3%, a return to normal daily activities and
      life such as eating and drinking habits, sleeping habits, or work-related
      aspects; (3) for 72.9%, an improvement in quality of life; (4) for 52.9%, a
      successful surgical intervention without any complications or side effects; and
      (5) for 48.6%, protection from a Barrett esophagus and cancer risk. In contrast,
      only two patients answered that they would expect normalization of pH values and
      healing of esophagitis. The data show that the majority of patients have clear
      expectations about laparoscopic antireflux surgery. These expectations are partly
      related to official medical treatment goals. In general, patient-related aspects
      of outcome concerning expectations should be included as a standard in all
      official goals of GERD treatment and also in medical outcome studies. One of
      these aspects should absolutely be patients' quality of life.

PMID- 12496544
TI  - Laparoscopic antiperistaltic versus isoperistaltic gastrojejunostomy for
      palliation of gastric outlet obstruction in advanced cancer.
AB  - The purpose of the study was to compare the impact of the peristaltic orientation
      of laparoscopic gastrojejunal anastomoses (LGJ) in patients with malignant
      gastric outlet obstruction (GOO) on postoperative delayed-return gastric emptying
      (DRGE) rates. GOO was defined as complete holdup of contrast at barium meal
      and/or failure of gastroscope to pass beyond stricture. DRGE was defined as
      inability to eat regular diet by day 10. Thirty-four patients undergoing
      antiperistaltic LGJ were compared with 21 patients undergoing isoperistaltic LGJ
      at two institutions during the same period. Thirty-day mortality was 5.4%, and
      median survival was 6.2 months. Thirty-day morbidity was 20%, and conversion rate
      was 3.6%. DRGE rates were increased after isoperistaltic LGJ (0 vs. 3; P < 0.05),
      but patient groups were not well matched for type of primary cancer (P < 0.05).
      All patients with DRGE resumed food intake 12 to 16 days after surgery. There
      were 21 admissions before death, with a reoperation rate of 11.5% and a recurrent
      GOO rate of 3.8%. Although no conclusions could be drawn about whether the
      peristaltic orientation of the anastomosis had a bearing on DRGE rates, LGJ
      resulted in an overall 6% rate of DRGE.

PMID- 12496545
TI  - Laparoscopic placement of hepatic artery catheter for regional chemotherapy
      infusion: technique, benefits, and complications.
AB  - Approximately 15% to 18% of patients diagnosed with colorectal cancers present
      with metastases confined to the liver. Although many may undergo a liver
      resection procedure, some will not be candidates for surgery or will have
      recurrence of liver disease within the first 2 years after liver metastasis
      resection. For this subset of patients, regional hepatic chemotherapy, including
      intra-arterial chemotherapy, has been shown to improve control of the disease
      and, in some cases, prolong survival. With the advent of laparoscopic surgery and
      its application to more and more advanced procedures, the possibility of
      laparoscopic placement of a chemotherapy infusion catheter in the hepatic artery
      with all the advantages of a minimally invasive approach appears to be a viable
      alternative in our hands. From November 1993 through February 2002, 20 patients
      (12 male, 8 female) successfully underwent laparoscopic placement of a hepatic
      artery infusion catheter at the Texas Endosurgery Institute. Correct placement of
      the catheter was confirmed by methylene blue injections via the hepatic artery
      catheter at the time of surgery. Chemotherapy was generally initiated in the
      immediate postoperative period. Mean age was 68.3 years (range, 46-82). Twelve of
      the patients (60%) had previously undergone abdominal surgery. There were 27
      major laparoscopic procedures performed at the time of hepatic artery catheter
      placement. There were no conversions to an open procedure. Mean operative time
      was 186 minutes (range, 125-280), and mean blood loss was 132 mL (range, 20-300).
      These values include the 27 major concurrent laparoscopic procedures performed at
      the time of catheter placement, including 18 cholecystectomies, 7 colectomies,
      and 2 liver resections. Median hospital stay was 3 days (range, 3-25), with a
      median return to regular diet of 3 days. There were no intraoperative
      complications and no deaths secondary to catheter placement. There were 2 late
      complications, for an overall rate of 10%. For all 17 patients with residual
      hepatic disease whose chemotherapy was successfully instituted, regression of the
      metastases was evident by abdominal computed tomographic criteria and CEA levels.
      Laparoscopic hepatic artery catheterization is both feasible and safe. It incurs
      all the benefits of a minimally invasive procedure and can be performed at the
      time of laparoscopic colectomy to avoid the necessity of a second procedure.

PMID- 12496546
TI  - Preoperative selective endoscopic retrograde cholangiopancreatography and
      laparoscopic cholecystectomy without cholangiography.
AB  - The aim of this study was to show that laparoscopic cholecystectomy can be
      performed safely without routine intraoperative cholangiography. We performed a
      retrospective analysis of 1750 consecutive patients (1170 females and 580 males
      with a mean age of 51 years) who underwent laparoscopic cholecystectomy between
      January 1991 and January 2000. In all, 193 patients (11%) were selected to
      undergo preoperative endoscopic retrograde cholangiopancreatography (ERCP) on the
      basis of several criteria for risk of stones. No patients underwent
      intraoperative cholangiography. ERCP allowed us to make a diagnosis of biliary
      stones in 62.7% (121 cases). Extraction of the stones was successful in 96% of
      the cases. In 12% of cases ERCP findings were normal; in the remaining 26.3%,
      useful diagnostic information was obtained. There were three complications
      (bleeding and pancreatitis) after endoscopy (complication rate: 1.5%).
      Laparoscopic cholecystectomy was successful in 92.7% of patients, with a
      postoperative morbidity rate of 3% (0.5% of major complications). There were no
      deaths in this series. During a mean follow-up of 60 months (range, 12-120), 7
      patients (0.43%) were found to have residual biliary stones (5 had not had
      preoperative ERCP). The study confirms the hypothesis that laparoscopic
      cholecystectomy can be safely performed without routine intraoperative
      cholangiography, with selective use of preoperative ERCP.

PMID- 12496547
TI  - Laparoscopic splenectomy for idiopathic thrombocytopenic purpura.
AB  - We conducted a retrospective multicenter study by questionnaire to evaluate the
      results of laparoscopic splenectomy for idiopathic thrombocytopenic purpura
      (ITP). Between 1991 and 1998, 209 patients with a mean age of 41.2 years (range,
      10-83) had a laparoscopic splenectomy for idiopathic thrombocytopenic purpura.
      Preoperatively, 178 patients (85%) underwent medical treatment aimed at achieving
      a satisfactory platelet count. Twenty-nine patients were obese, with a body mass
      index greater than 30%, and 14% were HIV-seropositive. The so-called hanging
      spleen technique in the right lateral decubitus position was used most often. The
      average duration of surgery was 144 minutes (45-360). This was significantly
      longer in cases of conversion (170 minutes; P < 0.01). The factors influencing
      the duration of laparoscopy were operator experience and patient obesity (P <
      0.01). A conversion was necessary in 36 cases (17.2%) because of hemorrhage. The
      conversion rate varied from 5.3% to 46.7%, depending on the surgical team. A
      multivariate analysis of factors disposing to conversion identified two causes:
      obesity and operator experience. One or more accessory spleens were found in 34
      patients (16.2%). The average weight of the spleens was 194.2 g. There were no
      deaths. There were no complications in 187 patients (89.5%), with a mean hospital
      stay of 6.1 days. Patients who did not require a conversion had a significantly
      earlier return of intestinal transit, used less analgesic, and had a shorter
      length of hospitalization. Overall morbidity was 10.5% (22 cases), due to
      subphrenic collections (7 cases), abdominal wall complications (6 cases), re
      intervention for actual or suspected hemorrhage or pancreatitis (3 cases),
      pneumopathology (2 cases) and others (4 cases). A multivariate analysis about
      morbidity shows a statistically significant difference in conversions (P < 0.05)
      but not in obesity or in surgeon's experience. Normal activity was achieved on
      average by the twentieth postoperative day--earlier if conversion was not
      required (18.4 versus 33.9 days). The average preoperative platelet count was
      92.7 x 10(9)/L (range, 3 to 444). Twenty patients had a count of less than 30 x
      10(9)/L and in this group the conversion rate was 30% (6 cases). Ninety-six
      patients were seen in the outpatient clinic, with an average follow-up time of
      16.2 months (3 to 72 months), and the average platelet count was 242 x 10(9)/L (6
      to 780). Eight patients (8.3%) were failures with a platelet count of <30 x
      10(9)/L. In the 20 patients with a preoperative platelet count <30 x 10(9)/L,
      there were 3 early failures and 5 late relapses. There were 2 late deaths: chest
      infection at 3 months in an HIV seropositive patient and one case of pulmonary
      embolus at 6 months. Laparoscopic splenectomy constitutes a real alternative to
      conventional splenectomy for the treatment of idiopathic thrombocytopenic
      purpura. It is associated with fewer postoperative complications, a shorter
      duration of hospitalization and an earlier return to normal activity. The
      limiting factors are the experience of the operator and patient obesity. The long
      term results are identical to those of conventional splenectomy, with a better
      than average success rate in patients that have failed preoperative medical
      treatment.

PMID- 12496548
TI  - Postoperative pulmonary dysfunction after bilateral inguinal hernia repair: a
      prospective randomized study comparing the Stoppa procedure with laparoscopic
      total extraperitoneal repair (TEPP).
AB  - The infraumbilical incision required for open repair of bilateral inguinal hernia
      with a giant prosthesis is associated with postoperative pain and respiratory
      impairment. The aim of this study was to evaluate the postoperative respiratory
      dysfunction after bilateral hernia surgery. Thirty-nine patients were randomized
      into two groups: open repair according to the Stoppa technique and laparoscopic
      extraperitoneal repair (TEPP). Respiratory function tests were performed before
      and 24 hours after surgery. The two groups were well matched for age, American
      Society of Anesthesiologists (ASA) risk score, type of hernia, and preoperative
      lung function. The postoperative forced vital capacity (FVC), peak expiratory
      flow (PEF), and forced expiratory volume in 1 second (FEV 1.0) were significantly
      altered in both groups. The PEF dropped 15% in both groups. The FVC dropped 22%
      after Stoppa versus 25% after laparoscopy (P = 0.7). The FEV 1.0 dropped 21%
      after Stoppa versus 9% after laparoscopy (P = 0.12). We conclude that
      laparoscopic preperitoneal and open bilateral hernia repair are followed by
      similar ventilatory dysfunction, although a trend toward better postoperative FEV
      1.0 was noted after laparoscopy. This might play a role in selected patients with
      severe pulmonary limitations. Overall, the limited drop in pulmonary function
      following bilateral hernia repair under general anesthesia may serve to explain
      the low pulmonary morbidity that follows these procedures.

PMID- 12496549
TI  - Endoscopic versus conventional open thyroid lobectomy for benign thyroid nodules:
      a prospective study.
AB  - The current study compared results between endoscopic thyroidectomy and
      conventional surgery in a prospective study. Twenty-two patients eligible for
      endoscopic thyroidectomy were evaluated. Patients were divided into group A, for
      conventional open thyroidectomy (n = 12), and group B, for endoscopic
      thyroidectomy (n = 10). Operative time, blood loss, postoperative complications
      and analgesic requirements, and time taken to return to normal activity were
      compared. Groups A and B were statistically balanced. Blood loss was
      significantly less in group B than in group A (11 versus 32 mL; P = 0.004), but
      no significant differences were observed in any of the other parameters. No
      postoperative complications (hemorrhage or recurrent laryngeal nerve paralysis)
      were present in either group. Compared with conventional surgery, endoscopic
      thyroidectomy for benign thyroid nodules was associated with less blood loss,
      although blood loss was minimal for both procedures. There were no practical
      differences in technical ability to perform.

PMID- 12496550
TI  - Rectus sheath hematoma complicating percutaneous endoscopic gastrostomy.
AB  - A case is reported of a rectus sheath hematoma occurring as an early consequence
      of percutaneous endoscopic gastrostomy with hemodynamic compromise. The most
      likely etiology is damage to the superior epigastric artery intraoperatively.
      Nonsurgical methods were used to achieve hemodynamic stability. This case
      illustrates an uncommon complication of gastrostomy tube placement that should be
      considered early postoperatively for patients with hemodynamic compromise.

PMID- 12496551
TI  - Gastroscopic-assisted laparoscopic cystogastrostomy in the management of
      pseudocysts of the pancreas.
AB  - Once pancreatic pseudocysts become persistent, unresolving, and symptomatic,
      surgical drainage is mandatory. Between January 1998 and December 2001, we
      performed five laparoscopic cystogastrostomies for such pseudocysts with the
      simultaneous use of the gastroendoscope. The mean cyst diameter was 20 cm (range,
      18.5-24). In the first four cases, the anterior wall of the stomach was entered
      through two 10-mm balloon cannulae under gastroscopic guidance. By introducing
      the laparoscope through one port and a harmonic scalpel through the other, a wide
      cystogastrostomy was performed. In the fifth case, a modification of the above
      technique was carried out. A single 10-mm cannula was used to enter the stomach
      and, with the use of a side-viewing gastroduodenoscope as the camera source, the
      harmonic scalpel was used to create the cystogastrostomy. The punctures in the
      wall of the stomach were repaired with endosutures. The gallbladder was removed
      in all cases. The mean operating time was 110 minutes (range, 92-128) for the
      combined procedure. There were no postoperative complications, and the mean
      hospital stay was 4 days. Postoperative follow-up with ultrasonography over a
      period of 1 year in each case revealed complete resolution of the cyst.
      Laparoscopic cystogastrostomy using harmonic scalpel under gastroscopic control
      is an effective and rapid method of surgically managing such lesions.

PMID- 12496552
TI  - Laparoscopic endogastric pseudocyst gastrostomy: a report of three cases.
AB  - The transgastric pseudocyst-gastrostomy is the standard approach for internal
      drainage of persistent and large retrogastric pancreatic pseudocysts that
      complicate acute necrotizing pancreatitis. We report on the application of a
      laparoscopic endogastric approach for drainage of pancreatic pseudocysts and
      discuss the merits of this technique as well as of the other previously described
      minimally invasive approaches for the management of pancreatic pseudocysts.
      Between January 2001 and August 2001, three female patients presented with large
      symptomatic pseudocysts 3-10 months after an episode of acute necrotizing
      pancreatitis. Internal drainage was effected by a laparoscopic endogastric
      pseudocyst gastrostomy, and the necrotic pancreas was debrided. There were no
      conversions and no postoperative complications. The median postoperative hospital
      stay was 4 days (range, 3-5). All patients remain asymptomatic, and resolution of
      the pseudocyst was radiologically evident at a median follow-up of 6 months
      (range, 4-11). The laparoscopic endogastric pseudocyst gastrostomy appears to be
      a safe and effective minimally invasive approach for internal drainage of large
      retrogastric pancreatic pseudocysts and facilitates debridement of the necrotic
      pancreas.

PMID- 12496553
TI  - Retained fecalith: laparoscopic removal.

PMID- 12496554
TI  - Torsion of the greater omentum: treatment by laparoscopy.
AB  - Four new cases of necrosis of the omentum secondary to torsion are reported. We
      review the associated signs and symptoms, which are usually those of an acute
      inflammatory condition in the right lower quadrant (RLQ), very similar to acute
      appendicitis. Because of acute abdominal pain in the RLQ, along with an uncertain
      diagnosis, laparoscopic surgery was performed in these cases. Laparoscopy
      demonstrated the existence of the omental infarction and allowed for complete
      treatment of the condition without the need for laparotomy.

PMID- 12496555
TI  - Laparoscopic repair of vaginal evisceration: a case report.
AB  - Vaginal evisceration, although rare, is usually present in postmenopausal women
      with a history of vaginal surgery and high-grade pelvic floor dysfunction.
      Operative management is directed toward resecting any compromised bowel,
      repairing vaginal defect, and correcting the defect in the pelvic floor, which is
      associated with most cases, either in the same intervention or in a second
      procedure. Laparoscopy allows for assessment of the viability of the compromised
      bowel and the vaginal defect suture with advantages common to minimally invasive
      techniques. We report the first case in the international literature of vaginal
      evisceration managed by laparoscopy.

PMID- 12496556
TI  - Laparoscopy-assisted resection of complicated Meckel's diverticulum.

PMID- 12496558
TI  - Extraction of the appendix after laparoscopic appendectomy.

PMID- 12496557
TI  - Outpatient laparoscopic incisional/ventral hernioplasty: our experience in 55
      cases by Moreno-Egea et al.

PMID- 12496560
TI  - A long-term retrospective outcome assessment of facial growth, secondary surgical
      need, and maxillary lateral incisor status in a surgical-orthodontic protocol for
      complete clefts.
AB  - In 1965, the cleft palate team at Children's Memorial Hospital embarked on a new
      surgical-orthodontic protocol in the habilitation of newborn complete cleft lip
      and palate cases. It brought the orthodontic effort into focus at birth and in
      planned sequence to correspond with the surgical procedures of lip closure,
      maxillary alveolar stabilization by means of an autogenous graft of the authors'
      design, and complete palate closure, all within the first year of life. The
      purpose of this investigation is threefold: first, to review the authors'
      previous publications and assess growth, secondary surgical need, and lateral
      incisor status of teeth adjacent to the cleft in a series of patients who have
      all followed a precise, early surgical/orthodontic protocol; second, to compare
      these cases with other collaborative studies wherein this protocol was not used;
      and third, to report on an additional 82 cases with regard to secondary surgical
      need and the status of teeth adjacent to the cleft. Methods of assessment have
      included cephalometric radiography, periapical and occlusal dental radiography,
      computer-assisted tomography, plaster cast analysis, and intraoral and extraoral
      photography. The authors have demonstrated, along with other collaborative
      studies, that there is growth as good as other similar samples wherein there was
      no primary osteoplasty. In addition, the authors found their incidence of
      orthognathic surgery to be 18.29 percent; pharyngoplasty, 3.65 percent; and
      oronasal fistulas requiring surgical closure, 29.27 percent. In the case of
      unilateral complete clefts, 53.13 percent of those lateral incisors present
      adjacent to the cleft area were usable, and in bilateral cases, 57.77 percent
      were usable. The authors remain convinced after more than 35 years of following
      this successful protocol that early maxillary orthopedics and their technique of
      primary osteoplasty in planned sequence with lip and palate closure can produce a
      more favorable alignment of maxillary growth potential and, with comprehensive
      orthodontic treatment, can lead to teeth in a better overall occlusion than if
      these procedures had not been undertaken.

PMID- 12496561
TI  - Lip height and lip width after extended Mohler unilateral cleft lip repair.
AB  - The purpose of this study was to evaluate the symmetry in lip height and lip
      width after extended Mohler unilateral cleft lip repair, with long-term follow-up
      monitoring. In the Mohler repair procedure, Millard's C-flap is used to fill the
      entire defect created by the downward rotation of the medial lip element. Because
      a lateral advancement flap is not transposed into this defect, Mohler repair is
      often expected to produce a short lip. In a retrospective study of 120 patients,
      anthropometric measurements were made on black-and-white photographs. Of those
      patients, 49 met the study criterion of having a set of photographs taken 13
      months or less postoperatively and another set taken at least 2 years
      postoperatively. The distance from the Cupid's bow peak to a line tangent to the
      base of the columella (lip height) and the distance from the Cupid's bow peak to
      the ipsilateral commissure (lip width) were measured with a Vernier caliper. The
      medial intercanthal distance was also measured, for standardization of all
      measurements. All values were normalized to the mean intercanthal distance at age
      6, as reported by Farkas. Matched-pair test analyses were used to assess the
      statistical significance of differences in cleft-side versus non-cleft-side
      measurements for each group, as well as changes with time. No statistically
      significant difference in cleft side versus non-cleft-side lip height for the two
      groups or with time was observed (< or =13 months, p = 0.28; >2 years, p = 0.08;
      change with time, p = 0.69). Statistically significant differences in lip width
      between the cleft side and the non-cleft side were observed for both time groups.
      The average difference in lip width at 1 to 13 months was 8.6 percent (p <
      0.001). The average difference in lip width at 2 years or more postoperatively
      was 5.8 percent (p < 0.001). In comparisons of early versus late measurements, it
      was noted that lip width significantly increased with time (mean, 0.91 mm; p =
      0.035). The findings suggest that extended Mohler repair does not produce a short
      lip. Interestingly, lip width was observed to be significantly smaller on the
      cleft side in the immediate postoperative period. However, this deficiency was
      observed to decrease significantly during long-term follow-up monitoring.

PMID- 12496562
TI  - Rigid fixation of the calvaria in craniosynostosis without using "rigid"
      fixation.
AB  - Early observations of intracranial translocation of metal wires, plates, and
      screws used for infant skull surgery have led some surgeons to investigate
      alternative forms of fixation. The purpose of this study was to review a series
      of infants and children in whom absorbable suture fixation was used as the sole
      method of fixation in cranial vault remodeling. Standard osteotomies were
      successfully modified to permit the use of this less rigid form of fixation. Over
      a 6-year period, 142 cranial vault procedures were performed, primarily for
      craniosynostosis, using absorbable sutures (2-0 polydioxanone). Patients who did
      not have absorbable suture fixation, or who had a combination of absorbable
      sutures with another form of fixation, were excluded from this review. Records
      were reviewed for results (assessed by both the treating surgeon and an
      independent anthropologist) and for complications. The average age of patients
      was 2 years, 7 months (range, 1 month to 16 years). The clinical results were
      judged as follows: grade I (excellent), 49 percent; grade II (minor
      imperfections), 48 percent; grade III (small surgical procedure needed), 2
      percent; and grade IV (complete reoperation required), 1 percent. Anthropologic
      results were similarly distributed: excellent, 36 percent; good, 56 percent;
      fair, 8 percent; and poor, 0 percent. Those 3 to 8 percent of patients who were
      found to have the poorest results were all noted to have syndromes, and it
      appeared that an inherent lack of growth was the primary basis for the low score.
      There were no deaths or major complications in this series of patients. The
      smaller complications identified were infections [four cases (2.8 percent)] and
      transient cerebrospinal fluid leak [two cases (1.4 percent)]. The most important
      factor in determining whether absorbable suture fixation was sufficient was the
      size of a preexisting calvarial defect. Although concerns have been raised about
      a possible link between absorbable suture fixation and subsequent poor
      reossification, no such association was noted in this review. The primary
      disadvantage of using absorbable sutures was the lack of rigidity provided.
      Advantages included lower costs, speed of application, and the absence of
      observed intracranial translocation. In conclusion, the use of absorbable suture
      fixation (with modifications in osteotomy design) was associated with both
      acceptable aesthetic outcomes and low complication rates. Craniofacial surgeons
      may wish to consider the use of absorbable sutures as another option for bone
      fixation in treatment of craniosynostosis.

PMID- 12496563
TI  - Dynamic restoration in Mobius and Mobius-like patients.
AB  - Mobius syndrome is classically characterized by bilateral facial nerve and
      abducens nerve paralysis in combination with limb defects. In the past 110 years,
      physicians diagnosed children as having the syndrome on the basis of
      heterogeneity of symptoms and used the term "Mobius syndrome" or "Mobius-like
      syndrome" for patients with multiple cranial nerve involvement. The cause and the
      exact pathogenesis of the syndrome still elude understanding. Genetic work-ups,
      radiological findings, and data from autopsies differ in their approaches and
      their findings of the basic causes of Mobius syndrome. In the international
      literature, about 301 case reports are found scattered through the past century.
      The appearance of the facial deformity is easy to recognize, because the Mobius
      patient is impaired in his or her ability to communicate nonverbally. Despite
      ophthalmologic problems, it is the search for a smile that brings these patients
      to the reconstructive surgeon. Over the past 100 years, surgical efforts
      attempted to improve the mask-like appearance by static and dynamic procedures,
      usually local muscle transpositions. Today, combinations of microsurgical
      procedures and aesthetic techniques are being used to restore some movement to
      the expressionless face of these patients by nerve and muscle transplantation.
      This article discusses the heterogeneity of Mobius syndrome, advocates a new
      classification system, presents the clinical findings of 42 patients who were
      seen and examined in consultation, and discusses the surgical management of 20
      patients who underwent dynamic restorative microsurgery. Exemplary cases
      illustrating the preoperative work-up regimen and possible outcomes are reported.

PMID- 12496564
TI  - Use of the radial forearm flap for deep, central, midfacial defects.
AB  - Six cases that required soft-tissue replacement in the central midface are
      presented. The greatest number of flaps were used for large defects in patients
      with cleft palates who had undergone multiple previous operations. Several were
      for palatal defects attributable to cocaine abuse, and one was used for lining in
      a nasal reconstruction. There were no flap losses and, on the basis of these
      experiences, it is concluded that this is an excellent method for providing soft
      tissue in these difficult situations.

PMID- 12496565
TI  - The dorsal scapular island flap: an alternative for head, neck, and chest
      reconstruction.
AB  - The back has become an increasingly popular donor site for flaps because it can
      provide thin, pliable tissue, with minimal bulk, and the scar can be easily
      hidden under clothing. The authors performed a cadaveric and clinical study to
      evaluate the anatomy of the dorsal scapular vessels and their vascular
      contribution to the skin, fascia, and muscles of the back. On the basis of
      anatomical studies in 28 cadavers and clinical experience with 32 cases, it was
      concluded that the dorsal scapular vessels provide a reliable blood supply to the
      skin of the medial back, making it a versatile flap to use as an island flap. A
      flap raised on the dorsal scapular vessels can be harvested with a long pedicle
      and can be rotated to reach as far as the anterior regions of the head, neck, and
      chest wall. Delaying and expanding the flap may help to facilitate venous
      drainage. The authors recommend the use of this versatile island pedicle flap as
      an alternative to microvascular free-tissue transfer for the reconstruction of
      defects in the head, neck, and anterior chest.

PMID- 12496566
TI  - Expression of basic fibroblast growth factor and transforming growth factor-Beta
      1 in patients with fasciocutaneous and muscle flaps.
AB  - Angiogenesis involves multiple sequential mechanisms stimulating the growth of
      host endothelium. It occurs in surgical flaps at the interface with the
      reconstructed wound bed. In this study, concentrations of basic fibroblast growth
      factor (bFGF) and transforming growth factor-beta 1 (TGF-beta ) were analyzed in
      sera and wound fluids of 30 patients who underwent surgical treatment with muscle
      (n = 15) and fasciocutaneous flaps (n = 15). At 12 hours after operation, bFGF
      levels in wound fluids of patients with muscle flaps were significantly (p <
      0.05) higher than in patients with fasciocutaneous flaps. At 24 and 36 hours
      after surgical treatment, there was no significant difference between them. Each
      group showed a significant decrease in bFGF levels after 24 and 36 hours. In
      sera, bFGF was not detectable. The two different groups presented no remarkable
      difference in TGF-beta concentrations in wound fluids. A correlation between
      angiogenic factors in sera and wound fluids could not be observed. The results
      show that angiogenesis is initially more activated in the wound bed of muscle
      flaps. This might be of great consequence to the healing process and might
      explain the curative effect of muscle flaps on bradytrophic tissue.

PMID- 12496567
TI  - Tissue and plasma levels of endothelin in free flaps.
AB  - The goal of the study was to assess whether endothelin-1 levels are increased in
      tissue and plasma in free flaps. To assess this hypothesis, blood samples were
      taken from the general circulation before and after reperfusion and from the flap
      after reperfusion in 20 patients undergoing breast reconstruction with free
      transverse rectus abdominis musculocutaneous or deep inferior epigastric
      perforator flaps. Tissue samples were also taken from the flap before and after
      the period of ischemia. Peripheral blood samples of 10 ml each were taken before
      the vessels were clamped and at 10 minutes and 1 hour after the flap was
      recharged. The flap vein was catheterized with a smooth catheter to avoid
      endothelial trauma, and ischemic blood from the flap was obtained immediately
      after the artery was unclamped and 10 minutes later. Two skin samples of 2 cm
      each were taken: one after dissection of the flap before division of the vessels
      and one after reanastomosis of the veins (one or two veins). Statistical analyses
      were performed with the (nonparametric) Wilcoxon signed rank test. Flap ischemia
      time, from vessel division to the completion of the arterial anastomosis, ranged
      from 35 to 120 minutes (mean, 48 minutes). The plasma endothelin-1 level
      extracted from the flap was 4.34 +/- 0.85 pg/ml, significantly higher than
      baseline, 3.87 +/- 0.81 pg/ml (p < 0.0001). There was a small increase, 4.5 +/-
      1.03 pg/ml (p = NS), 10 minutes after reperfusion. The peripheral level after
      venous anastomosis was 3.78 +/- 0.79 pg/ml, not significantly different from the
      peripheral plasma level, before the flap was raised. The peripheral plasma level
      1 hour after reperfusion was 3.83 +/- 0.8 pg/ml, with no difference from
      baseline. The tissue level of endothelin-1 before clamping was 3.8 +/- 0.8 pg/mg
      and in postischemic tissue, 5.2 +/- 0.6 pg/mg, a statistically significant
      increase. The authors concluded that endothelin-1 levels are elevated in free
      flaps. This could be an explanation for vasospasm and may lead to therapy
      directed against the no-reflow phenomenon.

PMID- 12496568
TI  - Vacuum assisted closure for the treatment of sternal wounds: the bridge between
      debridement and definitive closure.
AB  - A method to refine the treatment of sternal wounds using Vacuum Assisted Closure
      (V.A.C.) therapy as the bridge between debridement and delayed definitive closure
      is described. A retrospective review of 35 consecutive patients with sternal
      wound complications over a 2-year period (March of 1999 to March of 2001) was
      performed. The treatment of sternal wounds with traditional twice-a-day dressing
      changes was compared with the treatment with the wound V.A.C. device. An analysis
      of the number of days between initial debridement and closure, number of dressing
      changes, number and types of flaps needed for reconstruction, and complications
      was performed. Eighteen patients were treated with traditional twice-a-day
      dressing changes and 17 patients were treated with V.A.C. therapy alone. The two
      groups were similar regarding age, sex, type of cardiac procedure, and type of
      sternal wound. The V.A.C. therapy group had a trend toward a shorter interval
      between debridement and closure, with a mean of 6.2 days, whereas the dressing
      change group had mean of 8.5 days. The V.A.C. therapy group had a significantly
      lower number of dressing changes, with a mean of three, whereas the twice-a-day
      dressing change group had a mean of 17 (p < 0.05). Reconstruction required an
      average of 1.5 soft-tissue flaps per patient treated with traditional dressing
      changes versus 0.9 soft-tissue flaps per patient for those treated with V.A.C.
      therapy (p < 0.05). Before closure, there was one death among patients undergoing
      dressing changes and three in the V.A.C. therapy group, all of which were
      unrelated to the management of the sternal wound. Patients with sternal wounds
      who have benefited from V.A.C. therapy alone have a significant decrease in the
      number of dressing changes and number of soft-tissue flaps needed for closure.
      Finally, the V.A.C. therapy group had a trend toward a decreased number of days
      between debridement and closure.

PMID- 12496569
TI  - Anti-soya antibodies and trilucent breast implants.
AB  - In light of the media attention surrounding the withdrawal of Trilucent breast
      implants in March of 1999, we undertook a study of 20 women with these implants
      to compare the level of serum antibodies to soya oil and protein with that of a
      control group. Two control groups were chosen: 20 women without breast implants
      and 20 women with silicone-containing breast implants. Serum antibodies to soya
      protein were detected with an enzyme-linked immunoabsorbent assay technique,
      because direct assay to soya oil is not possible owing to insolubility of the
      soya oil component. No antibody formation was detected in the patients with
      Trilucent breast implants or in either of the control groups, lending support to
      the view that these implants are unlikely to give rise to a systemic immune
      response.

PMID- 12496570
TI  - Reduction mammaplasty: a prospective study of symptom relief and alterations of
      skin sensibility.
AB  - The aim of the present study was to evaluate the alterations of symptoms and
      tactile sensibility of the breast after reduction mammaplasty. In a prospective
      study, 10 women were operated on using the inferior pedicle technique. The
      patients were examined and interviewed preoperatively and at 2 weeks and 3 and 12
      months postoperatively. Tactile sensibility was assessed by Somedic monofilaments
      applied on nine points on each breast: the nipple, four points on the areola, and
      in four quadrants of the skin. Preoperative tactile sensibility was compared with
      tactile sensibility in 10 normal controls. A median of 744 g of tissue was
      removed. All patients reported relief of shoulder and neck discomfort and
      improvement of skin sensibility 1 year after the operation. Two weeks after the
      operation, the sensibility of the areola was reduced (p < 0.05), but the skin
      sensibility of two quadrants was improved (p < 0.05). The sensibility of the
      areola was restored to preoperative values during the observation period. At 12
      months, sensibility was improved compared with preoperative values both in the
      upper part of the areola and in three quadrants of the skin (p < 0.05).
      Significant improvement of skin sensibility was found between 3 and 12 months
      postoperatively in two quadrants of the breast. Also, the erectile function of
      the nipple was not altered by the operation. In conclusion, the sensibility of
      the breast was improved or unchanged 1 year after reduction mammaplasty using the
      Robbins technique. Continuous improvement of sensibility was found during the 1
      year observation period. The evidence provided by this prospective study rules
      out the common misconception that a reduction mammaplasty gives the patient
      reduced areola sensibility and altered erectile function.

PMID- 12496571
TI  - Routine drainage is not required in reduction mammaplasty.
AB  - To date, there have been no randomized trials documenting the efficacy of closed
      suction drainage when applied to reduction mammaplasty. Despite this, it has
      become the standard of care. A recent retrospective review suggests that closed
      suction drainage is not necessary. This study attempts to resolve this issue in a
      prospective, randomized fashion. The Institutional Review Board of the College of
      Medicine of The Pennsylvania State University approved the study. Forty-nine
      consecutive patients who underwent reduction mammaplasty by the inferior pedicled
      techniques were enrolled. Each patient was randomized to having a drain in either
      the right or left breast. The other breast was undrained. Patients were followed
      up for rate of complications and for patient satisfaction. Their ages ranged from
      17 to 62 years, with a mean of 33 years. Weight of reduction from the drained
      breasts ranged from 360 to 1090 g, with a mean reduction of 675 g. Weight of
      reduction from the undrained group ranged from 380 to 1011 g, with a mean of 620
      g. There were a total of 11 complications in the study. In the drained group,
      there were six complications out of 49 breasts (partial nipple loss in one, minor
      wound breakdown in two, fat necrosis in two, and hematoma in one). In the
      undrained group, there were five complications out of 49 breasts (partial nipple
      loss in none, minor wound breakdown in three, fat necrosis in one, and hematoma
      in one). Statistical analysis using the McNemar test revealed no significant
      difference between the two groups. A questionnaire revealed that the patients
      preferred the increased early postoperative comfort afforded by the absence of a
      drain. Performing reduction mammaplasty without the use of closed suction
      drainage is safe and is preferred by the patients.

PMID- 12496572
TI  - Skin-sparing mastectomy and immediate autologous tissue reconstruction after
      whole-breast irradiation.
AB  - Traditional breast conservation therapy consists of lumpectomy and whole-breast
      irradiation. Local recurrence after breast conservation is usually managed with
      salvage mastectomy. Skin-sparing mastectomy and immediate autologous tissue
      reconstruction is an accepted method of managing primary breast malignancies with
      exceptional aesthetic results. The purpose of this study was to evaluate this
      technique in the previously irradiated breast. This study is a retrospective
      review of all patients undergoing skin-sparing mastectomy and immediate
      reconstruction with autologous tissue after failed breast conservation therapy
      between 1995 and 1999. There were 11 patients with a mean age of 45 years (range,
      34 to 58 years). Initial lumpectomy was performed for ductal carcinoma in situ in
      six patients and infiltrating carcinoma (ductal or lobular) in five patients. The
      interval from lumpectomy to salvage mastectomy ranged from 12 to 169 months
      (mean, 44 months). Reconstructive techniques included unipedicled transverse
      rectus abdominis musculocutaneous (TRAM) flap (n = 4), free TRAM flap (n = 4),
      and latissimus flap with immediate placement of a saline implant (n = 3). Flap
      survival was 100 percent, and there were no early flap complications. One patient
      developed partial-thickness mastectomy flap loss (3 x 3 cm), which was managed
      conservatively. There were no instances of full-thickness mastectomy skin loss.
      Late complications included capsular contracture (n = 2), fat necrosis (n = 1),
      and ventral hernia (n = 1). There was one late death from metastatic disease; the
      remaining patients were without evidence of disease at a mean of 48 months
      (range, 30 to 75 months). Aesthetic results were judged as excellent (n = 4),
      good (n = 5), fair (n = 1), and poor (n = 1). These results demonstrate that skin
      sparing mastectomy and immediate autologous tissue reconstruction can be safely
      performed in patients with previous whole-breast irradiation. Clearly, patient
      selection is paramount with attention to the quality of the irradiated breast
      skin and the anatomic location of the recurrent disease. In this experience, the
      best results were seen after TRAM (pedicled or free) flap reconstruction.

PMID- 12496573
TI  - Immediate breast reconstruction using biodimensional anatomical permanent
      expander implants: a prospective analysis of outcome and patient satisfaction.
AB  - Immediate breast reconstruction is offered to the majority of women requiring a
      mastectomy for cancer treatment. Improvements in implant technology have seen the
      evolution of shaped, fixed-volume implants and permanent expanders. The
      theoretical benefits of biodimensional anatomical expander implants include
      better reconstructed breast form, the potential for achieving this at a single
      procedure, and the avoidance of a contralateral procedure as a result of improved
      ipsilateral cosmesis. The aim of the present study was to assess outcome after
      immediate breast reconstruction using the McGhan 150 permanent expander implant.
      A total of 107 consecutive patients (129 breast reconstructions) were studied
      over a 30-month period; 49 patients (68 reconstructions) had submuscular implant
      placement alone, and 58 patients (61 reconstructions) had an implant in
      conjunction with a latissimus dorsi flap. The mean patient age was 47 years
      (range, 22 to 72 years) and the mean follow-up was 18 months (range, 6 to 40
      months). Outcome was assessed in the following four ways: geometric measurements,
      evaluation of photographs by four independent observers, linear numerical
      analogue scale, and a quality-of-life questionnaire. Geometric measurements after
      surgery showed median differences that were highly consistent with good symmetry.
      Transverse breast width difference between breasts was 0.35 cm, vertical breast
      height difference was 0.8 cm, sternal notch-to-nipple distance difference was 0.6
      cm, midclavicular line-to-nipple distance difference was 0.5 cm, nipple-to
      inframammary crease distance difference was 0.5 cm, midline-to-nipple distance
      difference was 0 cm, and projection difference was 0 cm. Photographic assessment
      by four observers who evaluated shape, cleavage, symmetry, and overall outcome
      produced correlation values of 0.73 to 0.81. More than 75 percent of each of
      these parameters was scored as good or excellent. A numerical analogue scale
      (from 1 to 10) assessing overall result by the surgeon and patient revealed good
      (7 to 8) or excellent (9 to 10) scores in 83 and 82 percent of respondents,
      respectively. Quality-of-life data showed that 81 and 88 percent of women felt "a
      little" or "not at all" less feminine, respectively, and 88 percent were
      satisfied with the appearance of their breasts. A total of 88 percent of women
      would also choose the same reconstructive procedure if faced with the same cancer
      diagnosis. Complication rates were low; infections occurred in 6.2 percent of
      reconstructions, hematoma occurred in 1.6 percent, and implant loss occurred in
      3.9 percent. Only 24 of 107 patients (22 percent) elected to have a synchronous
      contralateral breast adjustment, and four of 107 (4 percent) chose to have a
      subsequent procedure for symmetry. Biodimensional expander implants used in
      immediate breast reconstruction are associated with high levels of patient and
      surgeon satisfaction. Optimum breast form can be achieved during a single
      operation with a low incidence of complications.

PMID- 12496574
TI  - Cryopreserved autologous nipple-areola complex transfer to the reconstructed
      breast.
AB  - If a patient's nipple-areola complex is available for grafting after mastectomy,
      it is the best material to use for nipple-areola reconstruction. The authors
      performed delayed autologous nipple-areola complex transfer to reconstructed
      breasts in 10 patients (mean age, 47 years; range, 40 to 53 years). The nipple
      areola complex was cryopreserved with a programmed freezer after mastectomy.
      Histological examination of the tissue surrounding the nipple and areola
      eliminated the possibility of cancer invasion. At the time of transfer, the
      cryopreserved nipple-areola complex was thawed in 37 degrees C water and grafted
      on a projection made by a denuded dermal flap on the reconstructed breast. Each
      patient underwent immediate breast reconstruction using an innervated pedicled
      transverse rectus abdominis musculocutaneous (TRAM) flap. The patients'
      postoperative courses were uneventful. The timing of transfer ranged from 3
      months to 1 year (mean, 5.8 months) after breast reconstruction. Nipple
      projection was made by the "four" dermal flap in five cases, a round dermal flap
      in three cases, a double dermal flap in one case, and a denuded skate flap in one
      case. The follow-up period ranged from 5 to 36 months (mean, 21.8 months). All
      grafts were adapted. The final evaluation of nipple-areola complex adaptation was
      good in four cases, fair in four cases, and poor in two cases. Histological
      examination of the hematoxylin and eosin stains showed no remarkable destruction
      of the skin of the nipple and areola, and electron microscopic examination of the
      areola skin revealed no significant change. However, electron microscopic
      examination of the nipple skin showed serious damage to skin components,
      including elongation of the desmosome, widening of the intercellular space at the
      prickle cell and basal layers, and shrinking of prickle and basal cells. Although
      further development of the freezing process and cryopreservation technique is
      needed to prevent depigmentation of the nipple and areola, cryopreserved nipple
      areola complex transfer to a reconstructed breast could be an alternative method
      of nipple-areola reconstruction.

PMID- 12496575
TI  - Safety and efficacy of office-based surgery with monitored anesthesia
      care/sedation in 4778 consecutive plastic surgery procedures.
AB  - Office-based surgery has several potential benefits over hospital-based surgery,
      including cost containment, ease of scheduling, and convenience to both patients
      and surgeons. Scrutiny of office-based surgery by regulators and state-licensing
      agencies has increased and must be addressed by improved documentation of safety
      and efficacy. To evaluate the safety and efficacy of the authors' office-based
      plastic surgery, a review was undertaken of 3615 consecutive patients undergoing
      4778 outpatient plastic surgery procedures under monitored anesthesia
      care/sedation in a single office. The charts of 3615 consecutive patients who had
      undergone office-based surgery with monitored anesthesia care/sedation between
      May of 1995 and May of 2000 were reviewed. In all cases, the anesthesia protocol
      used included sedation with midazolam, propofol, and a narcotic administered by a
      board-certified registered nurse anesthetist with local anesthesia provided by
      the surgeon. Charts were reviewed for patient profile, types of procedures,
      multiple procedures, duration of anesthesia, American Society of
      Anesthesiologists class, and complications related to anesthesia. Outcomes
      measured included death, airway compromise, dyspnea, hypotension, venous
      thrombosis, pulmonary emboli, protracted nausea and vomiting lasting more than 24
      hours, and unplanned hospital admissions. Statistical analyses were performed
      using the Microsoft Excel program and the SAS package. Results were as follows:
      92.3 percent of the patients were female and 7.7 percent were male, with a mean
      age of 42.7 years (range, 3 to 83 years). Patients underwent aesthetic (95.6
      percent) and reconstructive (4.4 percent) plastic surgery procedures. Same
      session multiple procedures occurred in 24.8 percent of patients. The vast
      majority of patients were healthy: 84.3 percent of patients were American Society
      of Anesthesiologists class I, 15.6 percent were class II, and 0.1 percent were
      class III. The operations required a mean of 111 minutes. There were no deaths,
      ventilator requirements, deep venous thromboses, or pulmonary emboli.
      Complications were as follows: 0.05 percent (n = 2) of patients had dyspnea that
      resolved, 0.2 percent (n = 6) of patients had protracted nausea and vomiting, and
      0.05 percent (n = 2) of patients had unplanned hospital admissions (<24 hours).
      One patient had an emergent intubation. No prolonged adverse effects were noted.
      There was a 30-day follow-up minimum. Outpatient surgery is an important aspect
      of plastic surgery. It was shown that office-based surgery with intravenous
      sedation, performed by board-certified plastic surgeons and nurse anesthetists,
      is safe. Appropriate accreditation, safe anesthesia protocols, and proper patient
      selection constitute the basis for safe and efficacious office-based outpatient
      plastic surgery.

PMID- 12496576
TI  - Adjacent and spontaneous neurotization after distal digital replantation in
      children.
AB  - In an exclusively pediatric population, this retrospective study examined the
      functional and aesthetic results after distal replantation without nerve suture.
      The aim was to demonstrate, in the child, the presence of spontaneous nervous
      regeneration resulting in a fingertip pulp with discriminatory sensation. Eight
      amputations in eight children with a mean age of 9 years and 2 months on the day
      of the accident were reviewed. The cases were managed by a single surgeon over a
      period of 8 years and were collected from two different hand centers. The
      patients were then examined by a different surgeon, and the data were collected.
      Sensibility was evaluated using the Weber, Semmes-Weinstein, and wrinkle tests.
      The results were excellent, with mean values of 4.6 mm for the Weber test, 3.3
      for the Semmes-Weinstein test, and a positive wrinkle test in all subjects. All
      patients thus recovered discriminatory sensation with minimal aesthetic sequelae.
      The usual factors adversely affecting the results of the replantation (ischemic
      time, level and mechanism of the amputation, and quality of the venous return)
      were examined, but no statistical analysis was performed because of the small
      sample size. This study demonstrates the presence of the clinical phenomenon of
      adjacent neurotization in the absence of nerve repair. It thus confirms that
      children are excellent candidates for replantation of the distal extremities,
      even when nerve suture is not performed.

PMID- 12496577
TI  - Nail regeneration by elongation of the partially destroyed nail bed.
AB  - Patients with partially destroyed fingernails tend to hide them, and such
      patients often do not find help because fingernails are considered of little
      functional value. To improve the aesthetic appearance of such nails, a simple
      excision of the destroyed nail matrix can stimulate the growth of the residual
      healthy matrix and regenerate the nail. Prerequisite is a healthy nail residue of
      at least the lunula. An excision of an en bloc, crescent-shaped, full-thickness
      scar, 5 mm at its greatest width and extending from one lateral nail fold to the
      other, increases the length of the nail plate. Together with the matrix, the nail
      will grow about 4 mm distally. A second crescent-shaped excision 1 to 2 months
      later will further lengthen the nail until it has gained full length. Normal nail
      growth was achieved in 11 patients who had partially scarred nail beds after
      mycosis or trauma.

PMID- 12496578
TI  - High-pressure hand injection injuries caused by dry cleaning solvents: case
      reports, review of the literature, and treatment guidelines.
AB  - A previously unreported subset of high-pressure injection injuries, namely those
      involving solvents used in the garment dry cleaning industry, is presented. Dry
      cleaning solutions contain isoparaffinic hydrocarbons, methoxypropanol, and
      dichlorofluoroethane. Although these solvents have limited potential for systemic
      toxicity, severe local toxicity causing tissue necrosis often results in loss of
      the injured digit. Proper treatment includes prompt surgical exploration, careful
      debridement and irrigation, intravenous antibiotics, and in selected cases, high
      dose systemic corticosteroids.

PMID- 12496579
TI  - Can angiogenesis induced by chronic electrical stimulation enhance latissimus
      dorsi muscle flap survival for application in cardiomyoplasty?
AB  - In cardiomyoplasty, the latissimus dorsi muscle is lifted on its primary
      neurovascular pedicle and wrapped around a failing heart. After 2 weeks, it is
      trained for 6 weeks using chronic electrical stimulation, which transforms the
      latissimus dorsi muscle into a fatigue-resistant muscle that can contract in
      synchrony with the beating heart without tiring. In over 600 cardiomyoplasty
      procedures performed clinically to date, the outcomes have varied. Given the data
      obtained in animal experiments, the authors believe these variable outcomes are
      attributable to distal latissimus dorsi muscle flap necrosis. The aim of the
      present study was to investigate whether the chronic electrical stimulation
      training used to transform the latissimus dorsi muscle into fatigue-resistant
      muscle could also be used to induce angiogenesis, increase perfusion, and thus
      protect the latissimus dorsi muscle flap from distal necrosis. After 14 days of
      chronic electrical stimulation (10 Hz, 330 microsec, 4 to 6 V continuous, 8
      hours/day) of the right or left latissimus dorsi muscle (randomly selected) in 11
      rats, both latissimus dorsi muscles were lifted on their thoracodorsal pedicles
      and returned to their anatomical beds. Four days later, the resulting amount of
      distal flap necrosis was measured. Also, at predetermined time intervals
      throughout the experiment, muscle surface blood perfusion was measured using
      scanning laser Doppler flowmetry. Finally, latissimus dorsi muscles were excised
      in four additional stimulated rats, to measure angiogenesis (capillary-to-fiber
      ratio), fiber type (oxidative or glycolytic), and fiber size using histologic
      specimens. The authors found that chronic electrical stimulation (1)
      significantly (p < 0.05) increased angiogenesis (mean capillary-to-fiber ratio)
      by 82 percent and blood perfusion by 36 percent; (2) did not reduce the amount of
      distal flap necrosis compared with nonchronic electrical stimulation controls (29
      +/- 5.3 percent versus 26.6 +/- 5.1 percent); (3) completely transformed the
      normally mixed (oxidative and glycolytic) fiber type distribution into all
      oxidative fibers; and (4) reduced fiber size in the proximal and middle but not
      in the distal segments of the flap. Despite the significant increase in
      angiogenesis and blood perfusion, distal latissimus dorsi muscle flap necrosis
      did not decrease. This might be because of three reasons: first, the change in
      muscle metabolism from anaerobic to aerobic may have rendered the muscle fibers
      more susceptible to ischemia. Second, because of the larger diameter of the
      distal fibers in normal and stimulated latissimus dorsi muscle, the diffusion
      distance for oxygen to the center of the distal fibers is increased, making fiber
      survival more difficult. Third, even though angiogenesis was significantly
      increased in the flap, cutting all but the single vascular pedicle resulted in
      the newly formed capillaries not receiving enough blood to provide nourishment to
      the distal latissimus dorsi muscle. The authors' findings indicate that chronic
      electrical stimulation as tested in these experiments could not be used to
      prevent distal latissimus dorsi muscle flap ischemia and necrosis in
      cardiomyoplasty.

PMID- 12496580
TI  - Analysis of fiber type transformation and histology in chronic electrically
      stimulated canine rectus abdominis muscle island-flap stomal sphincters.
AB  - Dynamic skeletal muscle flaps are designed to perform a specific functional task
      through contraction and relaxation of their muscle fibers. The most commonly used
      dynamic skeletal flaps today are for cardiomyoplasty and anal or urinary
      myoplasty. Low-frequency chronic stimulation of these flaps enables them to use
      their intrinsic energy stores in a more efficient manner through aerobic
      metabolic pathways for increased endurance and improved work capacity. The
      purpose of this study was to (1) determine whether fiber type transformation from
      fatigue-prone (type II) muscle fibers to fatigue-resistant (type I) muscle fibers
      could be demonstrated in the authors' chronic canine stomal sphincter model where
      the rectus abdominis muscle was used to create a functional stomal sphincter, (2)
      assess whether there is any correlation between the degree of muscle fiber type
      transformation and the continence times, and (3) examine the long-term effects of
      the training regimens on the skeletal muscle fibers through histologic and
      volumetric analysis. Eight dynamic island-flap sphincters were created from a
      part of the rectus abdominis muscle in mongrel dogs by preserving the deep
      inferior epigastric vascular pedicle and the most caudal investing intercostal
      nerve. The muscular sphincters were wrapped around a blind loop of distal ileum
      and trained with pacing electrodes. Two different training protocols were used.
      In group A (n = 4), a preexisting anal dynamic graciloplasty training protocol
      was used. A revised protocol was used in group B (n = 4). Muscle biopsy specimens
      were obtained before and after training from the rectus abdominis muscle
      sphincter. Fiber type transformation was assessed using a monoclonal antibody
      directed against the fatigue-prone type II fibers. Pretraining and posttraining
      skeletal muscle specimens were examined histologically. A significant fiber type
      conversion was achieved in both group A and group B animals, with each group
      achieving greater than 50 percent conversion from fatigue-prone (type II) muscle
      fibers to fatigue-resistant (type I) muscle fibers. The continence time was
      different for both groups. Biopsy specimens 1 cm from the electrodes revealed
      that fiber type transformation was uniform throughout this region of the
      sphincters. Skeletal muscle fibers within both groups demonstrated a reduction in
      their fiber diameter and volume. Fiber type transformation is possible in this
      unique canine island-flap rectus abdominis sphincter model. The relative design
      of the flap with preservation of the skeletal muscle resting length and neuronal
      and vascular supply are important characteristics when designing a functional
      dynamic flap for stomal continence.

PMID- 12496581
TI  - Expression of bone morphogenetic proteins during mandibular distraction
      osteogenesis.
AB  - Distraction osteogenesis is a form of in vivo tissue engineering in which the
      gradual separation of cut bone edges results in the generation of new bone. In
      this study, the temporal and spatial expression of bone morphogenetic proteins
      (BMPs) 2, 4, and 7 was examined in a rabbit model of mandibular distraction
      osteogenesis. Fourteen skeletally mature male rabbits were studied. After
      osteotomy, a distractor was applied to one side of the mandible. After 1 week of
      latency, distraction was initiated at 0.25 mm every 12 hours for 3 weeks
      (distraction period), followed by a 3-week consolidation period. Two animals were
      killed each week after surgery. The generate bone was analyzed for the expression
      of BMP-2, -4, and -7 by using standard bone histological and immunohistochemical
      techniques. BMP-2 and -4 were highly expressed in osteoblastic cells during the
      distraction period and in chondrocytes during the consolidation period. BMP-7
      demonstrated relatively minor expression in osteoblastic cells during the
      distraction period. All BMPs were strongly expressed in vascularized connective
      tissue during the distraction period. These data indicate that BMPs participate
      in the translation of mechanical stimuli into a biological response during
      mandibular distraction osteogenesis.

PMID- 12496582
TI  - Focal adhesion kinase expression during mandibular distraction osteogenesis:
      evidence for mechanotransduction.
AB  - Distraction osteogenesis is an established treatment strategy in the
      reconstruction of the craniofacial skeleton. The underlying mechanisms that drive
      bone formation during this process are largely unknown, but a regulatory role for
      mechanical force is believed to be critical. The integrin-mediated signal
      transduction cascade is a primary pathway by which signal transduction of
      mechanical stimuli (i.e., mechanotransduction) occurs. Focal adhesion kinase
      (FAK) is a significant regulator in this pathway. The authors hypothesize that
      mechanical forces created during distraction osteogenesis are responsible for the
      osteogenic response that takes place, and that these changes arise through
      integrin-dependent mechanotransduction. Using a rat model of distraction
      osteogenesis, the authors examined the expression of FAK in critical size defects
      (n = 15), subcritical size defects (n = 15), and mandibles undergoing distraction
      osteogenesis (n = 15). Their findings demonstrated FAK immunolocalization in
      mandibles undergoing distraction osteogenesis, but not in the critical size
      defects or in subcritical size defects, despite varying degrees of bone formation
      in the latter two groups. Furthermore, bone sialoprotein mRNA in situ
      hybridization patterns were found to mirror FAK immunolocalization patterns in
      mandibles undergoing distraction osteogenesis, demonstrating an association of
      FAK expression with the osteogenic process specific to distraction osteogenesis.
      These findings suggest that the bone formation in distraction osteogenesis is
      regulated by mechanical force by means of integrin-dependent mechanotransduction
      pathways.

PMID- 12496583
TI  - Vascularized acellular dermal matrix island flaps for the repair of abdominal
      muscle defects.
AB  - The potential widespread use of tissue-engineered matrices in soft-tissue
      reconstruction has been limited by the difficulty in fabricating and confirming a
      functional microcirculation. Acellular dermal matrix placed in a soft-tissue
      pocket acts as a scaffold to be incorporated by the host's fibrovascular tissue.
      A new method for noninvasive real-time observation of functional microvascular
      networks using orthogonal polarization spectral (OPS) imaging has recently been
      reported. Arterioles, venules, and capillaries can be directly visualized, and
      the movement of individual blood cells through them can be observed. The present
      study was performed to investigate the use of prefabricated acellular dermal
      matrix with an arteriovenous unit for the repair of abdominal muscle defects. OPS
      imaging was used to determine the presence of a functional microcirculation in
      the neovascularized matrix. In Sprague-Dawley rats, vascularized matrix was
      prefabricated by placing the superficial epigastric artery and vein on a 2-cm x 2
      cm implant-type acellular dermal matrix in the thigh. Three weeks after
      implantation, the matrix-arteriovenous unit was elevated as an axial-type flap
      and a 2-cm x 2-cm full-thickness block of abdominal muscle immediately superior
      to the inguinal ligament was resected. Additional procedures were performed
      according to group: no repair (group 1, n = 20); repair with nonvascularized
      acellular dermal matrix (group 2, n = 20); repair with devascularized acellular
      dermal matrix (group 3, = 20); and repair with vascularized acellular dermal
      matrix (group 4, n = 20). OPS imaging (field of view, 1 mm in diameter; scan
      depth range, 0.2 mm) was performed on both sides of each flap on a total of 10
      random distal regions before and after pedicle transection in group 3 and with
      the pedicle preserved in group 4. Hernia rate and duration of survival were
      compared for 21 days. OPS imaging showed directional blood cell movement through
      the capillary network in all areas scanned in group 4. No microvascular perfusion
      was observed after pedicle transection in group 3. Hernia rates of 100, 80, 90,
      and 0 percent were seen in groups 1, 2, 3, and 4, respectively. Median survival
      times of 9, 11.5, 9, and 21 postoperative days were noted in groups 1, 2, 3, and
      4, respectively. Histopathologic analysis with factor VIII revealed full
      thickness infiltration of the matrix by endothelial cells, signifying newly
      formed blood vessels. Repair of abdominal muscle defects using vascularized
      acellular dermal matrix resulted in no hernia and survival of all animals for the
      duration of study. However, repairs using avascular or devascularized matrix
      resulted in significant rates of hernia and decreased survival. Acellular dermal
      matrix can be prefabricated into vascularized tissue using an arteriovenous unit
      and used successfully to repair abdominal muscle defects. OPS imaging allowed for
      high-contrast direct visualization of microcirculation in previously acellular
      tissue following prefabrication with an arteriovenous unit.

PMID- 12496584
TI  - The optimal sequence of microvascular repair during prolonged clamping in free
      flap transfer.
AB  - During free flap transfer, the surgeon may decide to begin with repair of the
      artery or the vein(s) and to unclamp the first vessel as soon as repair is
      completed or maintain the clamping of both vessels until completion of all
      repairs. Complications can lead to prolonged clamping times, potentially
      increasing the risk of tissue ischemia, vascular damage, and thrombosis. The
      goals of the present study were to determine whether the sequence of vessel
      repair and the duration of clamping affect the success of free flap transfer in
      cases requiring prolonged clamping. Sixty abdominal fasciocutaneous free flaps
      based on the superficial inferior epigastric vessels were created in Sprague
      Dawley rats. To model clinical situations in which prolonged clamping is
      necessary, the study used a 1-hour delay before the repair of the second vessel.
      Flaps were randomized into four groups. In group I (n = 15), the artery was
      repaired first, and the arterial clamp was removed immediately to allow arterial
      inflow. In group II (n = 15), the arterial repair was first, and the arterial
      clamp was maintained until completion of venous repair. In group III (n = 15),
      venous repair was first, with venous clamping maintained until completion of the
      arterial repair. In group IV (n = 15), initial venous repair was followed by
      immediate unclamping, before arterial repair. On release of all clamps, the
      patency of arteries and veins was confirmed immediately and after 1 hour using a
      "milking" test. On the fifth postoperative day, each flap was assessed for
      necrosis and for patency of the anastomoses. Of 15 flaps in each group, five (33
      percent) failed in group I, four (27 percent) failed in groups II and III, and
      six (40 percent) failed in group IV. Differences between groups were not
      statistically significant (p = 0.8). These results demonstrate that in cases
      requiring prolonged occlusive clamping (2 to 3 hours), factors such as venous
      congestion, possible clamp injury, and presence of static blood in contact with
      the new anastomosis have relatively equivalent contributions to the risk of
      failure. Accordingly, no advantage seems to be gained by beginning with the
      artery or the vein or by using early or delayed unclamping of the first vessel
      repaired.

PMID- 12496585
TI  - Local hypothermia during early reperfusion protects skeletal muscle from ischemia
      reperfusion injury.
AB  - Amputated tissue maintained in a hypothermic environment can endure prolonged
      ischemia and improve replantation success. The authors hypothesized that local
      tissue hypothermia during the early reperfusion period may provide a protective
      effect against ischemia-reperfusion injury similar to that seen when hypothermia
      is provided during the ischemic period. A rat gracilis muscle flap model was used
      to assess the protective effects of exposing skeletal muscle to local hypothermia
      during ischemia only (p = 18), reperfusion only (p = 18), and both ischemia and
      reperfusion (p = 18). Gracilis muscles were isolated and exposed to hypothermia
      of 10 degrees C during 4 hours of ischemia, the initial 3 hours of reperfusion,
      or both periods. Ischemia-reperfusion outcome measures used to evaluate muscle
      flap injury included muscle viability (percent nitroblue tetrazolium staining),
      local edema (wet-to-dry weight ratio), neutrophil infiltration (intramuscular
      neutrophil density per high-power field), neutrophil integrin expression (CD11b
      mean fluorescence intensity), and neutrophil oxidative potential (dihydro
      rhodamine oxidation mean fluorescence intensity) after 24 hours of reperfusion.
      Nitroblue tetrazolium staining demonstrated improved muscle viability in the
      experimental groups (ischemia-only: 78.8 +/- 3.5 percent, p < 0.001; reperfusion
      only: 80.2 +/- 5.2 percent, p < 0.001; and ischemia-reperfusion: 79.6 +/- 7.6
      percent, p < 0.001) when compared with the nonhypothermic control group (50.7 +/-
      9.3 percent). The experimental groups demonstrated decreased local muscle edema
      (4.09 +/- 0.30, 4.10 +/- 0.19, and 4.04 +/- 0.31 wet-to-dry weight ratios,
      respectively) when compared with the nonhypothermic control group (5.24 +/- 0.31
      wet-to-dry weight ratio; p < 0.001, p < 0.001, and p < 0.001, respectively).
      CD11b expression was significantly decreased in the reperfusion-only (32.65 +/-
      8.75 mean fluorescence intensity, p < 0.001) and ischemia-reperfusion groups
      (25.26 +/- 5.32, p < 0.001) compared with the nonhypothermic control group (62.69
      +/- 16.93). There was not a significant decrease in neutrophil CD11b expression
      in the ischemia-only group (50.72 +/- 11.7 mean fluorescence intensity, p =
      0.281). Neutrophil infiltration was significantly decreased in the reperfusion
      only (20 +/- 11 counts per high-power field, p = 0.025) and ischemia-reperfusion
      groups (23 +/- 3 counts, p = 0.041) compared with the nonhypothermic control
      group (51 +/- 28 counts). No decrease in neutrophil density was observed in the
      ischemia-only group (40 +/- 15 counts per high-power field, p = 0.672) when
      compared with the nonhypothermic control group (51 +/- 28 counts). Finally,
      dihydrorhodamine oxidation was significantly decreased in the reperfusion-only
      group (45.83 +/- 11.89 mean fluorescence intensity, p = 0.021) and ischemia
      reperfusion group (44.30 +/- 11.80, p = 0.018) when compared with the
      nonhypothermic control group (71.74 +/- 20.83), whereas no decrease in
      dihydrorhodamine oxidation was observed in the ischemia-only group (65.93 +/-
      10.3, p = 0.982). The findings suggest a protective effect of local hypothermia
      during early reperfusion to skeletal muscle after an ischemic insult. Inhibition
      of CD11b expression and subsequent neutrophil infiltration and depression of
      neutrophil oxidative potential may represent independent protective mechanisms
      isolated to local tissue hypothermia during the early reperfusion period
      (reperfusion-only and ischemia-reperfusion groups). This study provides evidence
      for the potential clinical utility of administering local hypothermia to ischemic
      muscle tissue during the early reperfusion period.

PMID- 12496586
TI  - Protective effects of superoxide dismutase against ischemia-reperfusion injury:
      development and application of a transgenic animal model.
AB  - Reperfusion of ischemic tissues can be associated with structural and functional
      injury, which is referred to as ischemia-reperfusion injury. Superoxide dismutase
      is an endogenous free radical scavenger that converts toxic oxygen derived free
      radicals to hydrogen peroxide. With the development of gene cloning technology,
      the potential of manipulating cells to overexpress endogenous proteins has been
      realized. Transgenic mice capable of overexpressing superoxide dismutase, and
      knockout mice in which the gene responsible for its production has been deleted,
      were used as a model to examine the protective effects of superoxide dismutase
      against ischemia-reperfusion injury. Epigastric island flaps were elevated in
      wild-type (control), transgenic superoxide dismutase 1, and knockout superoxide
      dismutase 1 mice and subjected to ischemic intervals of 0, 3, 6, 9, or 12 hours.
      Five animals were studied at each time point in each study group. Flap viability
      was assessed on postoperative day 7. Baseline wild-type flap survival was 100
      percent after 3 hours of ischemia and subsequent reperfusion; survival decreased
      to 21 percent after 9 hours of ischemia. Transgenic mice had significantly higher
      flap survival than wild-type animals after 6 hours of ischemia and subsequent
      reperfusion (97.0 versus 85.2 percent) and after 9 hours of ischemia (82 versus
      21 percent, p < 0.01). In knockout mice, there was complete flap necrosis after
      as little as 3 hours of ischemia. This study confirms the protective effects of
      superoxide dismutase against ischemia-reperfusion injury. In addition, its
      deficiency results in a dramatic susceptibility to ischemic injury.

PMID- 12496587
TI  - A unique combination of infrared and microwave radiation accelerates wound
      healing.
AB  - Light or electromagnetic radiation has been reported to enhance wound healing.
      The use of selected spectra, including infrared and microwave, has been
      described; however, no studies to date have examined the potential benefit of
      combining these spectra. In this study, a device that emits electromagnetic
      radiation across both the infrared and microwave ranges was used. To test the
      effects of this unique electromagnetic radiation spectrum on wound healing, two
      clinically relevant wound-healing models (i.e., tensile strength of simple
      incisions and survival of McFarlane flaps) were selected. After the creation of a
      simple full-thickness incision (n = 35 rats) or a caudally based McFarlane flap
      (n = 33 rats), animals were randomly assigned to one of three treatment groups:
      untreated control, infrared, or combined electromagnetic radiation. Treatment was
      administered for 30 minutes, twice daily for 18 days in animals with simple
      incisions, and 15 days in animals with McFarlane flaps. The wound area or flap
      was harvested and analyzed, blinded to the treatment regimens. A p value of less
      than 0.05 obtained by analysis of variance was considered to be statistically
      significant. Animals receiving combined electromagnetic radiation demonstrated
      increased tensile strength (2.62 N/mm2) compared with animals receiving infrared
      radiation (2.36 N/mm2) or untreated controls (1.73 N/mm2, p < 0.001). Animals
      with McFarlane flaps receiving combined electromagnetic radiation had increased
      flap survival (78.0 percent) compared with animals receiving infrared radiation
      (69.7 percent) and untreated controls (63.1 percent, p < 0.01). Thus, combined
      electromagnetic radiation provided a distinct advantage in wound healing that
      might augment current treatment regimens.

PMID- 12496588
TI  - Preconditioning of latissimus dorsi muscle flaps with monophosphoryl lipid a.
AB  - The use of dynamic myoplasty to restore function to failing organs is an exciting
      new application of skeletal muscle flaps. A complication of large flap elevation
      that can compromise flap function is ischemia-induced necrosis; one approach to
      minimizing this is to pretreat tissues with ischemic preconditioning. The purpose
      of this study was to determine whether systemic administration of monophosphoryl
      lipid A, a drug known to mimic late-phase ischemic preconditioning in the heart,
      could reduce ischemia-induced necrosis in latissimus dorsi muscle flaps. Forty
      latissimus dorsi muscle flaps from 20 Sprague-Dawley rats were allocated into
      four groups. In group I (n = 10), flaps were not preconditioned and served as
      controls. In group II (n = 10), flaps received ischemic preconditioning with two
      30-minute periods of ischemia interspersed by 10 minutes of reperfusion. In group
      III (n = 10), rats received an intravenous bolus of approximately 0.3 ml of
      monophosphoryl lipid A vehicle only. In group IV (n = 10), rats received an
      intravenous bolus of 450 microg/kg of monophosphoryl lipid A and vehicle. Twenty
      four hours after treatment, all latissimus dorsi muscle flaps were elevated on a
      single neurovascular pedicle and subjected to 4 hours of ischemia. After 72 hours
      of reperfusion, latissimus dorsi muscles were harvested, weighed, stained with
      nitroblue tetrazolium, and assessed for percent necrosis using digitized images
      of muscle sections and computerized planimetry. The percent necrosis in ischemic
      preconditioning-treated flaps (group II) was significantly reduced by 57 percent
      (p < 0.05) compared with control flaps (group I). The percent necrosis in flaps
      treated with monophosphoryl lipid A (group IV) was significantly reduced by 58
      percent (p < 0.05) compared with vehicle-control flaps (group III). There was no
      difference in mean percent necrosis between ischemic preconditioning (group II)
      and monophosphoryl lipid A-treated (group IV) flaps or between ischemic
      preconditioning-control (group I) and monophosphoryl lipid A vehicle-control
      (group III) flaps. Intravenous administration of systemic monophosphoryl lipid A
      mimics the late-phase protective effect of ischemic preconditioning in the
      authors' rat latissimus dorsi muscle flap model.

PMID- 12496589
TI  - Prolongation of skin xenograft survival with modified cultured fibroblasts.
AB  - Cyclosporine A, one of the most potent immunosuppressive drugs, mediates some of
      its immunosuppressive and nephrotoxic effects by enhancing transforming growth
      factor-beta secretion and receptor expression. In this experimental study, the
      effect of cyclosporine pretreatment of cultured dermal fibroblasts on xenogeneic
      tissue rejection after microimplantation beneath skin grafts was investigated.
      The effects of the site-specific immunosuppressive strategy on skin xenograft
      survival were tested. Because the skin is an immunological indicator of the
      rejection of composite tissue allografts, it was considered that this strategy
      could be used as a supportive therapy for composite tissue allotransplantation in
      the future. In the first stage of the study, fibroblast cultures obtained from
      skin biopsy samples from five rats were treated with different single doses of
      cyclosporine (100 to 3000 ng/ml), and transforming growth factor-beta levels were
      measured in culture supernatants after 72 hours. In the second stage, 60 Sprague
      Dawley rats were divided into six groups, as follows. For group I (sham), only
      the standard grafting procedure was performed. For group II, after the standard
      grafting procedure, rats were treated with intraperitoneal injections of 30 mg/kg
      (n = 5) or 10 mg/kg (n = 5) cyclosporine for 10 days. For group III, cultured
      fibroblasts obtained from skin biopsy samples from rats were treated with 100 or
      500 ng/ml cyclosporine, and the cells were collected by light trypsinization and
      centrifugation after 72 hours. After the standard skin grafting procedure,
      modified fibroblasts were implanted between the graft and the recipient bed with
      a Pasteur pipet. For group IV, the same procedures as for group III were
      performed and then rats were treated with 10 mg/kg cyclosporine, administered
      intraperitoneally, for 10 days. For group V, in addition to standard grafting,
      unmodified fibroblasts (not treated with cyclosporine) were implanted between the
      graft and the recipient bed. For group VI, the same procedures as for group V
      were performed and then rats were treated with 10 mg/kg cyclosporine,
      administered intraperitoneally, for 10 days. The rejection process was observed
      macroscopically, and statistical significance was determined with the Mann
      Whitney test (p < 0.01). Graft survival times were significantly prolonged in
      groups III and IV, compared with groups I, II, V, and VI (p < 0.001). No
      difference between groups III and IV was observed. The novel finding of this
      investigation is that xenogeneic skin graft survival times could be prolonged
      with microimplantation of cyclosporine-treated cultured fibro-blasts.

PMID- 12496590
TI  - Induction of hard keratin expression in non-nail-matrical keratinocytes by nail
      matrical fibroblasts through epithelial-mesenchymal interactions.
AB  - Epithelium in the nail matrix is different from that at other body sites, in
      terms of clinical and histological appearance. Hard keratins are exclusively
      expressed in the nail matrix and bed and the hair apparatus, and hard keratin is
      considered a differentiation marker of these sites. Whether the expression of
      hard keratin in non-nail-matrical keratinocytes could be induced by nail-matrical
      fibroblasts was examined. Skin equivalents were constructed in three ways;
      ventral keratinocytes (from the ventral side of the digit) were cocultured with
      ventral fibroblasts (group A), ventral keratinocytes were cocultured with nail
      matrical fibroblasts (group B), and nail-matrical keratinocytes were cocultured
      with ventral fibroblasts (group C). Immunohistochemical examinations with anti
      hard keratin antibody (HKN-7) revealed hard keratin expression in groups B and C.
      HKN-7-positive cells were distributed continuously in the entire epithelial
      strata or in the suprabasal layer in group B, whereas HKN-7-positive cells were
      distributed spottily in group C. This study indicates extrinsic hard keratin
      induction in non-nail-matrical keratinocytes by nail-matrical fibroblasts and
      suggests that non-nail-matrical epidermal grafts may be effective in the
      treatment of deepithelized nail injuries. In addition, it is possible that lost
      nails could be reconstructed with grafts of "tissue-engineered" nail equivalent.

PMID- 12496591
TI  - Long-term immunologic induction of donor-specific tolerance to skin allografts by
      bone marrow transplant in rabbits.
AB  - The induction of donor-specific tolerance to skin allografts was investigated in
      rabbits using bone marrow transplantation techniques reported to be effective in
      mice. Various routes of bone marrow transplantation (i.e., intravenous, portal
      venous, or intraosseous) were also examined. In regimen A, the animals were
      treated with portal venous injection of bone marrow cells from the donor on day 0
      and intravenous injection of bone marrow cells from the same donor on
      posttransplant day 5. In regimen B, the animals were treated with portal venous
      and intraosseous injections of donor bone marrow cells on day 0 and intravenous
      injection of bone marrow cells from the same donor on posttransplant day 5. In
      regimen C, the animals were given intraosseous injection of donor bone marrow
      cells on day 0 and intravenous injection of bone marrow cells from the same donor
      on posttransplant day 5. It was found that regimens B and C were more effective
      than regimen A in prolonging allograft survival. The results demonstrate that
      induction of allograft tolerance can be achieved by bone marrow transplantation
      in a rabbit model. This protocol deserves further study in other large animal
      models.

PMID- 12496593
TI  - Breast reconstruction with prefabricated transverse rectus abdominis muscle flap
      in the postabdominoplasty patient.

PMID- 12496592
TI  - Venous interruption is unnecessary to achieve an adequate delay in the rat TRAM
      flap model.
AB  - Staged division of any or all inferior dominant pedicles to the human lower
      transverse rectus abdominis musculocutaneous (TRAM) flap has previously been
      attempted to invoke the delay phenomenon to enhance the rate of success with the
      superior-pedicled version, especially for patients at high risk for
      complications. Regardless of the specific vessels ligated, this has usually been
      accomplished by division of the source artery and its accompanying vein. Whether
      division of both vessels is essential remains unclear, however. This issue was
      investigated by using the authors' standard rat TRAM flap model in 43 female
      Sprague-Dawley rats, which were randomly assigned to four groups. In group A,
      both the predominant ipsilateral cranial epigastric artery and the cranial
      epigastric vein were divided 2 weeks before elevation of the TRAM flap. In group
      B, only the artery was divided; in group C, only the vein was divided. In an
      undelayed control group, the TRAM flap was elevated immediately, with no prior
      pedicle division. The percentages of flap survival in group A (89.3 +/- 7.0
      percent) and group B (88.8 +/- 6.5 percent) (both with division of the
      predominant artery) were significantly greater than that in the control group
      (64.6 +/- 20.5 percent) (p < 0.001) or that in the group in which the vein alone
      was divided (73.9 +/- 11.3 percent) (p < 0.01). There was no significant
      difference between the group that underwent vein division only and the control
      group (p = 0.102). The clinical implication is that arterial division is critical
      for TRAM flap delay and that arbitrary venous interruption is unnecessary.

PMID- 12496594
TI  - Large involuted facial hemangioma treated with syringe liposuction.

PMID- 12496595
TI  - Maxillofacial impalement by a hair-weaving instrument.

PMID- 12496596
TI  - Reconstruction of umbilical hypogenesis accompanied by a longitudinal scar.

PMID- 12496597
TI  - Reverse osteocutaneous dorsoulnar thumb flap.

PMID- 12496598
TI  - Musculocutaneous flexor carpi ulnaris flap for reconstruction of posterior
      cutaneotricipital defects of the elbow.

PMID- 12496599
TI  - Talking jejunum: a new, safe technique for voice reconstruction using free
      jejunum transfer.

PMID- 12496600
TI  - Botulinum toxin in the treatment of zygomatic fractures.

PMID- 12496601
TI  - The turnover subdermal-periosteal median forehead flap.

PMID- 12496602
TI  - Antegrade intramedullary fixation of displaced metacarpal fractures: a new
      technique.

PMID- 12496603
TI  - Pseudosyndactylic toe-to-hand transfer for simultaneous reconstruction of the
      thumb and index finger.

PMID- 12496604
TI  - Radial artery flow-through flap for distal lower-extremity arterial bypass for
      limb salvage.

PMID- 12496605
TI  - Hand resurfacing with the superthin latissimus dorsi perforator-based free flap.

PMID- 12496606
TI  - Wrap-around cartilage flap for the correction of unilateral cleft lip-nose
      deformity.

PMID- 12496607
TI  - Patient perception of neurosensory deficit after sagittal split osteotomy in the
      mandible.

PMID- 12496608
TI  - The transverse platysma myocutaneous flap for head and neck reconstruction: an
      update.

PMID- 12496609
TI  - Further experience with the sternocleidomastoid myocutaneous flap.

PMID- 12496610
TI  - Professor Edmund Rose: his position in surgery.

PMID- 12496611
TI  - Recurrent mammary hyperplasia: current concepts.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the factors leading to undesirable long-term reduction
      mammaplasty results. 2. Delineate the differential diagnosis of recurrent
      hypermastia. 3. Understand the significance of preoperative counseling,
      particularly with regard to expected postoperative outcome. 4. Understand short
      term and long-term expected and undesirable postoperative results. 5. Understand
      safe and effective surgical planning for revision reduction mammaplasty. A large
      majority of patients who undergo reduction mammaplasty are satisfied with their
      aesthetic outcome and resolution of preoperative symptoms. Occasionally, patients
      present with postoperative concerns; these are usually aesthetic in nature and
      caused by breast scarring, breast asymmetry, and/or breast shape. Inadequate
      excision and recurrent hypermastia are more complex concerns, which require
      careful evaluation and treatment. Analysis of both the presenting deformity and
      the original surgical approach is critical in determining an operative plan. This
      article discusses the safe approach to revision reduction mammaplasty. Current
      concepts are discussed and presented. An algorithm for decision-making is
      presented and discussed.

PMID- 12496612
TI  - Mandating shorter work hours and enhancing patient safety: a new challenge for
      resident education.

PMID- 12496613
TI  - Belt lipectomy for circumferential truncal excess: the University of Iowa
      experience.
AB  - When some patients with circumferential truncal excess undergo traditional
      abdominoplasty, the trunk is not addressed as a unit. Belt lipectomy, a procedure
      that combines abdominoplasty with circumferential excision of skin and fat, is
      often more ideal for these patients. In this article, the authors review the
      literature on belt lipectomy and evaluate their series of 32 patients who
      underwent belt lipectomy at the University of Iowa. The evolution and current
      preoperative markings, intraoperative surgical technique, and postoperative care
      are described. The patients' charts and their preoperative and postoperative
      photographs were examined retrospectively. It was found that belt lipectomy
      improved abdominal contour, abdominal wall laxity, mons pubis ptosis, back rolls,
      waist contour, and buttocks contour. Initially, the procedure was performed on
      post-weight-reduction patients only, but its indications were extended to three
      other groups: patients who were 30 to 50 pounds overweight, patients of normal
      weight who desired a significant overall truncal improvement, and an obese
      patient with persistent intraabdominal excess. The improvements were significant
      in all groups of patients except for the latter patient. Complications included a
      37.5 percent seroma rate, a 9.3 percent pulmonary embolus rate, and one
      dehiscence that required reoperation. The authors concluded that belt lipectomy
      should be seriously considered for patients who present with circumferential
      truncal excess and for a select group of normal-weight patients. It is not
      recommended for the obese patient with excessive intraabdominal content.
      Furthermore, belt lipectomy should be undertaken only in patients who are well
      informed about the possible risks and complications.

PMID- 12496614
TI  - Hair transplantation for men with advanced degrees of hair loss.
AB  - In the field of surgical hair restoration, there is probably no greater challenge
      than treating the individual with advanced male pattern hair loss. Recent
      developments in follicular unit grafting and recognition of the natural
      appearance of the transplanted frontal forelock have now made it possible to
      obtain excellent, undetectable results in these patients. Over a 22-month period,
      the onset correlating with the time when the author began to use the technique of
      follicular unit grafting, 61 of 322 hair transplant procedures (approximately 20
      percent) performed for male pattern hair loss were on men with, or at high risk
      of developing, advanced male pattern hair loss. Uniformly, the creation of some
      type of frontal forelock provided excellent results and high patient
      satisfaction. The concept of the frontal forelock is not new. Developments in
      aesthetic principles, enhanced understanding of its applicability, and the
      applied advantages of follicular unit grafting allow for the first time, truly
      undetectable results.

PMID- 12496615
TI  - Is there evidence for excessive free radical production in vivo during ultrasound
      assisted liposuction?
AB  - The surgical technique of ultrasound-assisted liposuction has become a standard
      procedure for the treatment of lipodystrophy. However, little is known about the
      impact of this therapy on fatty tissue on the molecular level. There are concerns
      about possible adverse effects related to the high-intensity ultrasound energy,
      because in vitro studies have shown a substantial generation of free radicals. In
      this study, the authors investigated whether ultrasound waves can create an
      excessive free radical production in vivo by measuring lipid peroxidation
      products in the form of malondialdehyde equivalents. For this purpose, the
      thiobarbituric acid-reactive substances (TBARS) assay was chosen. In this test,
      malondialdehyde, a major product of lipid peroxidation, reacts with
      thiobarbituric acid to produce a pink adduct that can be measured
      spectrophotometrically. The authors determined oxidation products in 28 aspirates
      of 17 treated patients before ultrasound-assisted liposuction (0 minutes) to
      establish a baseline concentration and at 2, 5, and 10 minutes after the
      treatment was begun. Median malondialdehyde concentration of the control group
      (conventional liposuction, 0 minutes) was 3.40 nmol of malondialdehyde per gram
      of adipose tissue. Median concentrations after 2, 5, and 10 minutes of ultrasound
      assisted liposuction were 7.45 (n = 28), 8.84 (n = 21), and 4.07 (n = 8) nmol
      malondialdehyde per gram adipose tissue, respectively. The differences were not
      statistically significant. The data suggest that there is no excessive formation
      of lipid oxidation products in response to free radicals. The antioxidative
      capacity of adipose tissue does not seem to be overwhelmed by the standard
      application regimen of ultrasound-assisted liposuction.

PMID- 12496616
TI  - Intraoperative tissue expansion in rhytidectomy revisited.
AB  - Intraoperative tissue expansion is an adjunct that has been used during
      rhytidectomy to rejuvenate the face and neck. This technique has been thought to
      allow for additional skin resection and, thus, increased skin tightening during
      rhytidectomy. The stretch of the skin by expansion should allow for additional
      skin resection before closure. Also, when the force of the underlying expander is
      removed, the expanded skin would recoil and the advancement of the flap should
      become tighter, with improved results. The technique achieved some popularity a
      few years ago but has received little recent attention. In this study, the
      authors attempted to compare face-lift results of adjunctive intraoperative
      tissue expansion during rhytidectomy with similar techniques without
      intraoperative expansion. The results of 50 female patients who underwent
      rhytidectomy for midface rejuvenation by a single operating surgeon composed the
      study group. Twenty-five of the patients had undergone rhytidectomy that
      addressed the cheek, chin, and neck areas without expansion (nonexpanded
      rhytidectomy group). The other 25 patients (expanded rhytidectomy group) had
      adjunctive intraoperative tissue expansion performed with the rhytidectomy. A
      tissue expander was temporarily placed beneath the rhytidectomy flaps on each
      side and expanded in a standard manner before final skin resection and closure.
      Frontal and lateral photographs were evaluated by 54 examiners. Preoperative and
      postoperative photographs of the 50 patients were viewed side-by-side by the
      examiners. The patients were presented in blind fashion and random order. The
      examiners graded the results of each patient on a scale of improvement from 1 to
      10, with 10 being the maximum level of improvement. The scores were recorded and
      statistically evaluated by using the two-sample test. Evaluation of the
      examiners' scores showed that the mean rating given to patients in the expanded
      rhytidectomy group was 5.07 (SD = 1.12). The mean rating for the nonexpanded
      rhytidectomy group was 5.27 (SD = 1.57). When the two groups were compared using
      the two-sample test, the difference between the two was not statistically
      significant (p = 0.6127). Intraoperative tissue expansion as an adjunct to
      rhytidectomy did not result in improved facial rejuvenation in this patient
      series. The authors' impression is that the benefits of tissue expansion do not
      justify the added expense, time, and risks associated with using tissue expansion
      during rhytidectomy.

PMID- 12496617
TI  - Restoring palpebral fissure shape after previous lower blepharoplasty.
AB  - The youthful palpebral fissure can be described as long and narrow. Both the
      aging process and transcutaneous lower blepharoplasty can cause descent of the
      lower lid margin and medial migration of the lateral canthus, resulting in a
      rounding of the palpebral fissure. This article presents a technique to correct
      significant postsurgical lower lid malposition and palpebral fissure distortion
      without the use of outer or inner lamellar grafts. In overview, subperiosteal
      dissection frees scarred lid structures and cheek soft tissues, creating a
      continuous composite flap. Elevation of the cheek soft tissues recruits deficient
      outer lamellae and allows the sub-orbicularis oculi fat to be positioned between
      the orbital rim and scarred lid structures, filling this space and helping to
      support the repositioned lid margin. Titanium screws placed in the lateral orbit
      provide a point for secure fixation of elevated cheek tissues. Transosseous wire
      fixation securely repositions the lateral canthus. This procedure not only
      restores lower lid position and the vertical height of the palpebral fissure, but
      it also restores the palpebral fissure's horizontal length and the lateral
      canthal angle. It has been effective in correcting palpebral fissure distortion
      after lower blepharoplasty in 15 patients during a 6-year period.

PMID- 12496618
TI  - Intraoral approach for reduction malarplasty: a simple method.
AB  - Young Korean women with prominent zygoma may experience stress in daily life
      because the Oriental physiognomy often associates prominent zygoma with bad luck.
      Moreover, prominent zygoma in a wide Oriental face has the effect of making a
      person appear older and stubborn. Zygomatic reduction is often necessary to
      relieve stress from self-consciousness about facial appearance and to obtain
      younger and softer features. As such, most zygomatic procedures are cosmetic;
      therefore, an entirely intraoral approach with no skin incision is desirable. The
      current operative method of zygomatic reduction consists of two steps. The
      zygomatic body and arch are exposed through a mucoperiosteal incision from the
      maxillary canine to the first molar area. The first step is to grind and file the
      zygomatic body. The second step is made on the zygomatic arch. Using an
      oscillating saw, a partial-thickness osteotomy is made just posterior to the
      orbital rim, and a full-thickness osteotomy is made just anterior to the
      articular tubercle of the zygomatic arch. Light pressure on the posterior part of
      the arch produces a greenstick fracture of the anterior osteotomy site and a
      complete fracture of the posterior osteotomy site, resulting in inward
      repositioning of the zygomatic arch. This method of zygomatic reduction is
      simple, easy, effective, and leaves no conspicuous scars on the face.

PMID- 12496619
TI  - Endoscopically assisted malarplasty: one incision and two dissection planes.
AB  - Asian society is uniquely concerned about the distinctive facial features
      associated with malar prominence. Various methods of reduction malarplasty have
      been developed and are currently being applied. In this study, a new approach to
      malarplasty was experimentally assessed between December of 1999 and August of
      2001. After having received careful observations of their facial features and
      full counseling sessions, 32 patients were selected. These patients had three
      distinctive characteristics: (1) severe zygomatic arch prominence and normal
      zygomatic body prominence, (2) desire for only a reduction of the lateral
      prominence, and (3) desire for a less invasive surgery. Through a short incision
      in the temporal area, the authors performed the dissection as two different
      planes. Endoscopic dissection between the superficial layer of deep temporal
      fascia and the temporoparietal fascia to the zygomatic body and blunt dissection
      under the deep layer of the deep temporal fascia to the zygomatic arch were
      performed. Complete osteotomy of the zygomatic arch and an incomplete osteotomy
      of the zygomatic body were then performed with a reciprocating saw. Finally, the
      zygomatic arch for the zygoma infraction was pressed manually. The major
      advantages of this procedure are its simplicity and the short operation and
      recovery time, with little bleeding and edema.

PMID- 12496620
TI  - Measuring outcomes in aesthetic surgery: a comprehensive review of the
      literature.
AB  - Outcomes research examines the end results of medical interventions, taking into
      account patients' experiences, preferences, and values. The purpose of assessing
      outcomes is to provide evidence on which to base clinical decisions. The
      assessment of outcomes in aesthetic surgery is especially pertinent because
      patient satisfaction is the predominant factor in determining success. In
      cosmetic surgery, various scales have been used to assess outcomes.
      Unfortunately, none of these methods has achieved widespread use. The adoption of
      broadly accepted, relevant scales to measure outcomes would be advantageous,
      because this would allow the comparison of techniques, quantification of positive
      effects, and identification of patients unlikely to benefit from surgery. The
      purpose of this study was to critically review the present literature to identify
      the appropriate instruments to assess outcomes in aesthetic surgery. After a
      comprehensive review of aesthetic surgery outcome instruments, the authors
      identified body-image and quality-of-life measures to be of the greatest value in
      determining aesthetic surgery outcomes. These conclusions were based on a
      critical evaluation of the feasibility, validity, reliability, and sensitivity to
      change of these measures. The Multidimensional Body-States Relations
      Questionnaire (MBSRQ), a psychological assessment of body image, was selected as
      a potential candidate for further study. Two additional body-image assessment
      instruments, the Facial Appearance Sorting Test (FAST) and the Breast Chest
      Ratings Scale (BCRS), may be useful in the assessment of rhinoplasty and breast
      surgery, respectively. The Derriford Scale (DAS59), an instrument that assesses
      appearance-related quality of life, was also selected. In addition, the authors
      recommend the use of a generic, utility-based quality-of-life instrument, such as
      the Health Utilities Index (HUI) or the EuroQol (EQ-5D).

PMID- 12496621
TI  - An economic analysis of health care reform and its implications for plastic
      surgery: a five-year perspective.

PMID- 12496622
TI  - Skin potions, stem cells, and growth hormones: the economic costs of selling
      patients dubious products and services.

PMID- 12496623
TI  - Panning for gold.

PMID- 12496624
TI  - A method for anchoring muscle slips in temporalis transposition for facial
      reanimation.

PMID- 12496625
TI  - A new method for securing skin grafts in pediatric patients.

PMID- 12496626
TI  - Bio-Alcamid, a novel prosthetic polymer, does not interfere with morphological
      and functional characteristics of human skin fibroblasts.

PMID- 12496627
TI  - Assessing technical skills of plastic surgeons.

PMID- 12496628
TI  - One-stage facial contour augmentation with intraoral transfer of a paraumbilical
      perforator adiposal flap.

PMID- 12496630
TI  - The double-opposing Deaver retractors as a mammastat in reduction mammaplasty.

PMID- 12496629
TI  - Bloodless pedicle deepithelialization in reduction mammaplasty.

PMID- 12496631
TI  - Deflating a breast prosthesis before operation.

PMID- 12496632
TI  - Skin-sparing mastectomy with nipple-areola conservation.

PMID- 12496634
TI  - Proposal for a variant of the Duhamel technique of preputioplasty.

PMID- 12496633
TI  - Defamation law: implications for medical authors.

PMID- 12496635
TI  - Treatment of thermal injuries from the CO2 laser.

PMID- 12496636
TI  - A subperiosteal harvest of rib myo-osseous composite flap.

PMID- 12496637
TI  - A novel, triple-function vessel dilator.

PMID- 12496638
TI  - The efficacy of laboratory studies in the detection of recurrent melanoma.

PMID- 12496639
TI  - Improving digital imaging.

PMID- 12496640
TI  - Syndactyly repair in Kindler syndrome.

PMID- 12496641
TI  - Use of posterior calf fascial flap: a new concept for the management of knee
      contracture with unstable scar.

PMID- 12496642
TI  - Modified horizontal mattress suture technique for closure of large and deep
      defects.

PMID- 12496643
TI  - A technique to aid in rib cartilage excision for access to the internal mammary
      vessels.

PMID- 12496644
TI  - Breast implant evaluation: pitfall of magnetic resonance imaging.

PMID- 12496645
TI  - Leech resistance: how to deal with it.

PMID- 12496646
TI  - The Martin-Whiston hand table.

PMID- 12496647
TI  - Painful injections with Botox.

PMID- 12496648
TI  - Oat cell lung cancer diagnosed following metastasis to the skin.

PMID- 12496649
TI  - Peroneal nerve injury caused by fracture of the distal femoral shaft.

PMID- 12496650
TI  - Who decides the criteria?

PMID- 12496651
TI  - Constructive skepticism--case in point: liposuction breast reduction.

PMID- 12496652
TI  - Painless postoperative period and drain removal using local anesthesia.

PMID- 12496653
TI  - Need for public and medical awareness of pediatric craniofacial trauma in Sierra
      Leone.

PMID- 12496654
TI  - Use of keloid cutis as reconstructive flap of the auricle after keloid excision.

PMID- 12496655
TI  - Fascial extension of the free radial forearm flap to cover the anastomosis site.

PMID- 12496656
TI  - Primary intraosseous hemangioma of the zygomatic bone.

PMID- 12496657
TI  - Incidental finding of subfascial/subaponeurotic lipoma during abdominoplasty.

PMID- 12496658
TI  - Applications of cell therapy to whole kidney replacement.

PMID- 12496659
TI  - Notch signaling in kidney development.
AB  - PURPOSE OF REVIEW: Notch signaling is a highly conserved mechanism used by
      multicellular animals to specify cell fate decisions during the formation of
      complex structures such as the kidney. A number of studies have recently
      identified requirements for Notch signaling during kidney organogenesis and
      tissue repair. This review will summarize these studies and compare Notch
      signaling in the mammalian kidney with Notch signaling in other organ systems.
      RECENT FINDINGS: A targeted mutation in the mouse Notch2 receptor resulted in
      kidneys that are devoid of glomerular endothelial and mesangial cells. The mutant
      epithelial cells of the developing glomerulus have reduced amounts of vascular
      endothelial growth factor expression, which may be responsible for the lack of
      vascularization observed in these glomeruli. Notch2 is expressed in the
      epithelial cells of the developing glomerulus, and a potential ligand, Jagged1 is
      expressed in the endothelial cells of the glomerulus. Mice simultaneously
      heterozygous for mutations in both Notch2 and Jagged1 phenocopy the kidney
      defects seen in mice homozygous for the Notch2 mutation. These doubly
      heterozygous mice also display liver and heart developmental abnormalities
      reminiscent of Alagille's syndrome. SUMMARY: Notch signaling is required for
      kidney development, and the expression of Notch genes is increased in response to
      kidney damage. Further studies of Notch signaling will be important in order to
      understand kidney development and tissue repair.

PMID- 12496660
TI  - The signals that drive kidney development: a view from the fly eye.
AB  - PURPOSE OF REVIEW: Development of the mammalian kidney is a complex process
      involving numerous signals and signaling pathways. Other complex tissues have
      benefited enormously from studies in lower, simpler organisms. The present review
      provides an update on what we have learned from the fruitfly Drosophila
      melanogaster, and argues that Drosophila is an important but under-utilized
      organism for study of renal development. RECENT FINDINGS: The Malpighian tubules
      provide renal function to the fly. These require a number of signaling pathways
      for their development that are also seen in vertebrate kidney development,
      including the Notch, Ras, and Wnt signaling pathways, as well as nuclear factors
      such as Kruppel and Cut/Cux-1. Many of these factors are shared between early
      Malpighian tubule development and ureteric bud formation. The Ret signaling
      receptor, which is central to mammalian renal development, is poorly understood
      in flies, although its expression pattern is intriguing. Surprisingly, other
      signaling factors such as Neph-1, Pax2, and Wilms' tumor suppressor-1 appear to
      work within later fly retinal development, providing a surprising link between
      these two disparate tissues. SUMMARY: Drosophila offers a powerful palate of
      tools for dissecting developmental processes. Importantly, these tools can often
      be examined at the level of single cells, permitting us to address issues of
      differentiation with high resolution. If we are to take full advantage of
      Drosophila, however, then we must target specific issues and gain a better
      understanding of the details of Malpighian tubule development.

PMID- 12496661
TI  - Hox genes and kidney patterning.
AB  - PURPOSE OF REVIEW: Hox gene activity is essential for proper organization or
      pattern of the vertebrate body plan and is necessary for organogenesis. Sequence
      conservation within this family of genes is high yet they are involved in very
      diverse developmental processes. How this family functions in these processes is
      a challenging question, but is important for the understanding of renal
      organogenesis. Multiple Hox genes are expressed in the kidney and mutation in at
      least one group of paralogous genes results in severe renal defects. RECENT
      FINDINGS: Recent studies in mice with targeted Hox gene mutations and in kidney
      cell lines demonstrate that these genes have evolved to control tissue specific
      functions through their ability to regulate the expression of renal morphogens.
      The studies also demonstrate that Hox gene activity is not only restricted by the
      domain of expression but also by the specificity of the DNA binding homeodomain.
      Interestingly, these conserved homeodomains are not wholly interchangeable for
      normal renal organogenesis while they do appear to be interchangeable for axial
      skeleton development. SUMMARY: It is clear that Hox genes regulate important
      interactions between the ureteric bud and metanephric mesenchyme. Nevertheless,
      much work remains to define the expression patterns of multiple Hox genes during
      kidney development, to better determine the functional relationships of the
      encoded proteins, and to identify additional Hox downstream targets.

PMID- 12496662
TI  - Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal
      tubule cells.
AB  - PURPOSE OF REVIEW: Emerging evidence suggests that tubular epithelial
      myofibroblast transdifferentiation is an important event in renal
      tubulointerstitial fibrosis. This review describes the recent findings in the
      context of the tubular epithelial-myofibroblast transdifferentiation process and
      discusses the possible mechanisms involved. RECENT FINDINGS: Tubular epithelial
      myofibroblast transdifferentiation is a complex process involving disruption of
      polarized tubular epithelial cell morphology into cells with spindle-shaped
      mesenchymal morphology, formation of actin stress fibers, loss of cell-cell
      adhesions through downregulation of E-cadherin, destruction of basement membrane,
      and increased cell migration and invasion. This phenotypic transition has also
      been recently reported in human glomerulonephritis with progressive
      tubulointerstitial fibrosis. Transforming growth factor-beta is a key fibrogenic
      growth factor that regulates tubular epithelial-myofibroblast
      transdifferentiation, which is counter-regulated by hepatocyte growth factor. In
      addition, basic fibroblast growth factor, advanced glycation end products, and
      angiotensin II have also been reported to induce the process. Importantly, the
      recent discovery of transforming growth factor-beta/Smad signaling has allowed
      the delineation of the intracellular mechanisms of tubular epithelial
      myofibroblast transdifferentiation. Indeed, Smad signaling is a key pathway
      whereby transforming growth factor-beta and angiotensin II induce tubular
      epithelial-myofibroblast transdifferentiation in vitro. This involves the
      activation of transforming growth factor-beta receptor-associated Smad2 and is
      inhibited by an inhibitory Smad protein, Smad7. Thus, Smad signaling plays a
      critical role in tubular epithelial-myofibroblast transdifferentiation. SUMMARY:
      Renal myofibroblasts may be derived from tubular epithelial cells by a process of
      tubular epithelial-myofibroblast transdifferentiation. Transforming growth factor
      beta signals through Smads to positively or negatively regulate this process.
      Blockade of this process by either hepatocyte growth factor or targeting the Smad
      signaling pathway may provide novel therapeutic strategies to combat renal
      fibrosis.

PMID- 12496663
TI  - Shear-stress-responsive signal transduction mechanisms in renal proximal tubule
      cells.
AB  - PURPOSE OF REVIEW: Phenotypic alterations resulting from flow-induced mechanical
      strains is a growing field of research in many cell types such as vascular
      endothelial and smooth muscle cells, chondrocytes or osteocytes. Although it has
      been acknowledged for several decades that tubular flow is a main determinant of
      tubular behavior in terms of vectorial transport of water and solutes, the effect
      of flow on other characteristics of proximal tubular cell phenotype was ignored
      until recently. The purpose of the review is to summarize the various effects of
      shear-stress, recently demonstrated in renal proximal cells. RECENT FINDINGS: New
      results demonstrate that tubular flow has pleiotropic effects on proximal tubular
      cells, affecting, in vitro and in vivo, the organization of the cytoskeleton, the
      synthesis of extracellular matrix proteases and the activity of specific
      transcription factors. SUMMARY: These results suggest that flow-induced
      mechanical strains could be one determinant of tubulointerstitial lesions during
      the progression of renal diseases.

PMID- 12496664
TI  - The parathyroid hormone-related protein system: more data but more unsolved
      questions.
AB  - PURPOSE OF REVIEW: The present review focuses on recent studies that might be
      considered as the most relevant advances in the parathyroid hormone-related
      protein field, with special emphasis on proven functions in renovascular and
      cardiovascular systems, in physiological as well as pathological conditions.
      Thus, the questions as to whether and how parathyroid hormone-related protein
      intervenes in vascular development and homeostasis and in vascular diseases such
      as hypertension, atherosclerosis, restenosis and heart failure have begun to be
      unraveled. RECENT FINDINGS: Since its discovery from hypercalcemia-associated
      tumors in 1987, it has become clear that parathyroid hormone-related protein is a
      ubiquitously expressed poly-hormone and plays crucial roles in normal life. The
      early lethality to parathyroid hormone-related protein knockout mice emphasizes
      the crucial roles of the protein in development but has limited the use of these
      models. However, data accumulated from transgenic animals overexpressing the
      protein in particular cells have provided considerable support to its
      physiological and pathological relevance. The recent demonstration that nascent
      parathyroid hormone-related protein not only follows the secretory pathways, but
      also directly translocates to the nucleus, is beginning to uncover new actions
      for the protein in a number of physiological systems such as bone, mammary gland
      and vascular smooth muscle, as well as in pathological situations, such as
      cancer, osteoporosis, sepsis, atherosclerosis and hypertension. SUMMARY: The
      development of mice with conditionally deleted parathyroid hormone-related
      protein or parathyroid hormone-1 receptor alleles will allow the creation of cell
      or tissue-specific parathyroid hormone-related protein knockout mice which will
      greatly facilitate the determination of the biological relevance of this protein
      in a specific cell or tissue type, particularly in the cardiovascular system.

PMID- 12496665
TI  - Vascular endothelial growth factor: a new player in the pathogenesis of renal
      fibrosis.
AB  - PURPOSE OF REVIEW: There is new and emerging evidence that renal vascular changes
      contribute to progressive renal disease and that alteration of vascular
      endothelial growth factor might play an important role in modulating
      microvascular loss or macrovascular remodeling in the kidney. RECENT FINDINGS:
      Microvascular endothelial loss both in glomerular and peritubular capillaries of
      progressive renal disease is directly linked to impaired blood flow, the
      development of renal ischemia and scarring. Vascular endothelial growth factor is
      a proliferative survival factor for endothelial cells, which could preserve
      stressed endothelium or stimulate angiogenesis, stabilize renal function and slow
      histologic progression as shown in different animal models of progressive renal
      disease. However, there has been some evidence for the mitogen playing a role in
      the development and progression of atherosclerosis via a mechanism that amplifies
      the inflammatory reaction. Whether vascular endothelial growth factor is
      detrimental in early stages of diabetic nephropathy or other renal conditions is
      not yet clearly answered. SUMMARY: Despite dramatic progress in current knowledge
      of vascular biology in progressive renal disease, there are still controversies
      about the mechanism by which vascular endothelial growth factor works in the
      kidney in different conditions and at different time points. We suggest it is now
      time to think of integral effects of this angiogenic factor as a new player in
      renal fibrosis with its potential therapeutic implication.

PMID- 12496666
TI  - The renin receptor: the facts, the promise and the hope.
AB  - PURPOSE OF REVIEW: The renin-angiotensin system plays a major role in the control
      of blood pressure and of salt balance, but it is also involved in physiological
      and pathological processes, development, inflammation and cardiac hypertrophy. A
      concept has emerged suggesting that these effects are due to a local activation
      of the renin-angiotensin system. The search for a receptor of renin was based on
      the idea that tissue (pro)renin is taken up from the circulation and on data
      suggesting that renin has cellular effects independent of angiotensin II. RECENT
      FINDINGS: Endothelial cells and cardiac myocytes bind (pro)renin via the mannose
      6-phosphate receptor, mainly a clearance receptor as no cellular effect has been
      specifically attributed to prorenin binding. A functional receptor was cloned
      recently. It mediates intracellular signalling by activating the mitogen
      activated protein kinases, extracellular signal regulated kinases 1 and 2, and
      acts as a co-factor by increasing the efficiency of angiotensinogen cleavage by
      receptor-bound (pro)renin. The receptor is abundantly expressed in heart, brain,
      placenta and eye, compared with a lower expression in liver and kidney. In normal
      human kidney and heart, it is localized in the mesangium and in the coronary and
      kidney artery, associated with smooth-muscle cells and co-localized with renin.
      SUMMARY: This receptor provides a functional role for prorenin and may help to
      understand the physiological and pathological role of elevated levels of prorenin
      and of local activation of the renin-angiotensin system. From a practical point
      of view, it questions the need for a pharmacological compound blocking (pro)renin
      binding and activity as an alternative to the classical inhibitors of the renin
      angiotensin system.

PMID- 12496667
TI  - Blood pressure and cardiovascular risks: implications of the presence or absence
      of a nocturnal dip in blood pressure.

PMID- 12496668
TI  - Pharmacogenomics of hypertension.
AB  - PURPOSE OF REVIEW: The emerging field of pharmacogenomics has the potential to
      fundamentally change the management of essential hypertension, a common, perhaps
      polygenic syndrome characterized by substantial inter-individual variability in
      drug responsiveness. As understanding of sequence diversity in the human genome
      progresses, the prospect grows for tailoring the prescription of antihypertensive
      drugs to complement common genetic variations among individual patients, allowing
      optimization of blood pressure control and improved avoidance of drug side
      effects. Some principles of pharmacogenomics are presented here, along with a
      review of the most recent literature on genetic determinants of antihypertensive
      drug responses, with a preview of likely developments to come. RECENT FINDINGS:
      Polymorphisms at candidate pharmacodynamic loci (such as angiotensinogen,
      angiotensin converting enzyme, and the angiotensin II receptor) have already been
      shown to predict responses to such specific treatments as angiotensin converting
      enzyme inhibition and angiotensin II blockade. The National Institutes of Health
      have established a multi-institutional pharmacogenetics network and knowledge
      base, whose goals include understanding how common polymorphisms influence
      therapeutic responses to a variety of drugs, including antihypertensive agents.
      SUMMARY: The study of genetic determinants of drug responses, particularly at the
      pharmacodynamic (drug target/receptor and post-receptor) level, is likely to
      allow us to more precisely tailor therapy to the individual patient, as well as
      to promote the creation of novel therapies.

PMID- 12496669
TI  - Kidney disease, genotype and the pathogenesis of vasculopathy.
AB  - PURPOSE OF REVIEW: The two leading causes of end-stage renal disease in the
      United States are diabetes mellitus and hypertensive nephrosclerosis, accounting
      for over two-thirds of all cases. In many patients both diseases are associated
      with small- and large-vessel disease, commonly attributed to hypertension or
      accelerated atherosclerosis. Recent investigations, however, have suggested that
      renal large-vessel and microvascular disease may be independent contributors to
      progressive kidney failure. RECENT FINDINGS: Although genes have not been
      definitely linked to renal vascular disease, population- and family-based
      epidemiology of kidney disease, segregation analysis of Pima and Caucasian
      families in which diabetic nephropathy is clustered, and the positional cloning
      of genes responsible for rare, familial glomerulosclerosis syndromes support the
      hypothesis that genes regulate the pathogenesis of renal disease. This review
      highlights developments in our current understanding of vasculopathy and its role
      in renal disease, and it summarizes evidence suggesting that genetic determinants
      for the vascular phenotype are associated with common causes of chronic renal
      failure. SUMMARY: With the application of genomics and proteomics methodologies
      to drug discovery, the identification of renal susceptibility genes should
      identify new mechanisms of progressive renal disease pathogenesis and generate
      novel target molecules for the treatment of kidney disease.

PMID- 12496670
TI  - Blood pressure, antihypertensive therapy and risk for renal injury in African
      Americans.
AB  - PURPOSE OF REVIEW: African-Americans are more likely than Caucasians to develop
      hypertension-related end-stage renal disease. Elevations in blood pressure levels
      clearly potentiate pre-existing renal disease and also contribute to kidney
      injury independently of other primary renal diseases in this cohort. Until
      recently, data relevant to a full examination of the issue of blood pressure
      levels and end-stage renal disease in African-Americans have largely been from
      post-hoc analyses of clinical trials or from small, prospective, short-term
      studies. RECENT FINDINGS: The most recent United States Renal Data Systems data
      show hypertension as the primary cause of end-stage renal disease in African
      Americans until 1997, diabetes now being the most prevalent etiology. Data from
      post-hoc analyses of the Modification of Diet in Renal Disease study demonstrated
      that African-Americans with a mean arterial pressure above 98 mmHg had a higher
      risk of end-stage renal disease than Caucasians. The African-American Study of
      Kidney Disease tested the hypothesis that a blood pressure well below the usual
      recommended level will further reduce renal disease progression in African
      Americans. The study concluded that a blood pressure lower than that needed to
      reduce cardiovascular events, as defined by the Sixth Joint National Committee
      Report on the Detection, Evaluation and Treatment of High Blood Pressure, i.e.
      135-140/80-85 mmHg, will not further slow renal disease progression in African
      Americans with hypertensive nephrosclerosis. Moreover, a regimen of blood
      pressure lowering anchored on angiotensin-converting enzyme inhibitors,
      antihypertensive agents that are touted as ineffective in African-Americans, was
      more effective than one based on either beta-blockers or dihydropyridine calcium
      channel blockers in slowing the progression of renal injury. SUMMARY: Systolic
      blood pressure reduction in the range 130-139 mmHg is appropriate to reduce risk
      of nephropathy progression and cardiovascular risk in African-Americans with
      hypertensive nephrosclerosis. Moreover, a regimen that is initiated with an
      angiotensin-converting enzyme inhibitor should be the antihypertensive treatment
      of choice in African-Americans with kidney disease.

PMID- 12496671
TI  - The role of adhesion molecules and T cells in ischemic renal injury.
AB  - PURPOSE OF REVIEW: The pathophysiology of ischemic acute renal failure is
      complex, incompletely understood and there are no specific therapies. Descriptive
      observations in human acute renal failure, as well as mechanistic studies in
      animals, have demonstrated an important pathophysiological role for leukocytes
      and leukocyte adhesion molecules. The purpose of this review is to summarize and
      interpret the recent advances on the role of T cells and leukocyte adhesion
      molecules in ischemic acute renal failure. RECENT FINDINGS: Emerging data suggest
      that the T cell is involved in modulating the outcome of ischemic acute renal
      failure, as well as ischemic injury to other organs. These new data build on the
      established role of inflammation in acute renal failure, and identify novel
      therapeutic targets. In addition, identification of the role of the T cell in the
      immediate injury response extends current immunological models of T cell
      function. Studies on leukocyte adhesion in acute renal failure have now
      identified the selectins and their ligands as important components of the
      inflammatory response to ischemic injury. SUMMARY: The identification of T cells
      and new adhesion molecule pathways as modulators of ischemic acute renal failure
      offers novel and feasible therapeutic opportunities for both native and
      transplant acute renal failure. Rigorous clinical trials are required to
      translate these basic findings to the bedside. In addition, mechanistic studies
      are needed to elucidate the molecular mechanisms by which these pathways modulate
      kidney injury. The identification of T cell engagement in ischemic renal injury
      can also help explain long-standing observations linking alloantigen-independent
      and alloantigen-dependent renal damage.

PMID- 12496672
TI  - Strokes and their relationship to hypertension.
AB  - PURPOSE OF REVIEW: There is rapidly growing appreciation that stroke morbidity
      and the risk of an ischaemic stroke becoming haemorrhagic can be influenced by
      new information about prophylaxis, rapid diagnosis and treatment. RECENT
      FINDINGS: Strokes are strongly associated with hypertension mainly because
      hypertension is strongly associated with atheromatous deposits blocking or
      narrowing brain arteries, predisposing to local clot formation. Atheroma and its
      ischaemic consequences may damage cerebral arterioles and the brain tissue they
      supply. Cerebral infarcts are more common than spontaneous cerebral haemorrhages.
      High blood pressure itself cannot directly rupture cerebral blood vessels because
      their small size protects them and intracerebral haemorrhage usually follows
      previous ischaemic vascular damage. It is obvious that lowering blood pressure
      would reduce the risk and extent of bleeding into the brain once a break in an
      arteriolar wall has occurred, but it is not clear why lowering blood pressure
      should protect against cerebral infarction. One might expect that slowing down
      the rate of cerebral blood flow would give more time for local clots to form. It
      seems most likely that induced hypotension protects against ischaemic strokes by
      preventing pressure- or ischaemia-induced arteriolar spasm and by advantageous
      vasodilation of some of the more ischaemic territories. Added protection can be
      provided by coenzyme-A reductase inhibitors (statins), but probably not by
      antioxidants. SUMMARY: Lowering blood pressure strongly protects against
      ischaemic and haemorrhagic stroke. Recent work shows that more accurate and
      faster diagnosis of stroke pathology is urgently needed, so that appropriate
      treatment (e.g. with tissue plasminogen activators) can be started before local
      bleeding has occurred.

PMID- 12496673
TI  - Sleep disorders and the failure to lower nocturnal blood pressure.
AB  - PURPOSE OF REVIEW: The failure to lower systolic blood pressure at night (called
      non-dipping) and sleep apnea are both associated with adverse cardiovascular
      outcomes. Sleep apnea is a common cause of non-dipping blood pressure. RECENT
      FINDINGS: Sleep apnea increases night time blood pressure through enhanced
      cardiac pre-load, sleep disturbance and hypoxia. Hypoxia elicits increased levels
      of norepinephrine, endothelin and erythropoetin. Patients with sleep apnea tend
      to be elderly and obese, so they have poor endothelial nitric oxide release and
      blunted baroreflexes. They thus have several stimuli for high blood pressure and
      poor compensatory mechanisms to lower blood pressure. SUMMARY: Non-dipping
      patients without sleep apnea have evidence of volume overload and correct their
      blood pressure pattern in response to diuretics. Individuals with sleep apnea
      have evidence of increased cardiac pre-load from episodes of negative
      intrathoracic pressure. Their daytime blood pressure responds poorly to many
      drugs, but beta blockers may be effective. Their night time blood pressure
      responds only slightly to therapy of their sleep apnea with continuous positive
      airway pressure, even though continuous positive airway pressure decreases their
      norepinephrine, erythropoetin and endothelin levels.

PMID- 12496674
TI  - Clues to ageing from cells, organs and outer space.

PMID- 12496675
TI  - The US Department of Agriculture Food Pyramid; the birth and aging of an idea.

PMID- 12496676
TI  - Body composition in aging: a biological perspective.
AB  - PURPOSE OF REVIEW: Changes in body composition accompany and predict medical and
      surgical risk; interventions may be considered. Aging affects body composition,
      particularly in reduction of the body cell mass. RECENT FINDINGS: The molecular
      biology of aging has become an active frontier of research in the past 30 years,
      with acceleration in the past decade. A review of the toxicities of reactive
      oxygen and nitrogen species, especially at the mitochondria, can now be studied
      at the molecular, genetic, and proteomic scales, in individual cell components
      and systems, with major implications for patient management, for planning
      therapeutic interventions, and for predicting future age spans. SUMMARY: The
      intersections between the clinical fields of endocrinology, nuclear
      medicine/radiology, and geriatrics, with the more fundamental fields of
      physiology, molecular biology, genetics, and proteomics are indicated.

PMID- 12496677
TI  - Inflammatory response in the elderly.
AB  - PURPOSE OF REVIEW: During ageing there may be the onset of a chronic inflammatory
      state. This review examines the underlying causes of this phenomenon and the role
      that genotype plays in its intensity. RECENT FINDINGS: There are predisposing
      factors for the chronic inflammation that occurs during ageing. These include
      increased oxidative stress, a decrease in ovarian function, a decrease in stress
      induced glucocorticoid sensitivity of pro-inflammatory cytokine production in
      men, and an increased incidence of asymptomatic bacteriuria. Obesity induces
      chronic inflammation. Inflammation is a key factor in the progressive loss of
      lean tissue and impaired immune function observed in ageing. Polymorphisms in the
      promoter regions of pro- and anti-inflammatory cytokine genes influence the level
      of cytokine production and the ageing process. Thus, a genotype for high pro
      inflammatory cytokine production results in high cytokine production and may
      accelerate the rate of tissue loss. Conversely, polymorphisms in the genes for
      anti-inflammatory cytokines may result in a slowing of tissue loss. In the
      healthy aged male population, the former polymorphisms are under-represented and
      the latter over-represented, indicating a genetically determined survival
      advantage in maintaining inflammation at a low level. Nutrients with anti
      inflammatory properties, such as vitamin E and n-3 polyunsaturated fatty acid,
      may reduce the level of chronic inflammation and thereby ameliorate tissue and
      functional loss during ageing. New evidence suggests that, for the latter
      nutrient, gene-nutrient interactions occur that alter the effectiveness of
      dietary therapy. SUMMARY: Ageing is associated with increased levels of chronic
      inflammation. This plays a major role in the decline in immune function and lean
      body mass. Anti-inflammatory nutrient therapy may slow the rate of decline. The
      pro- and anti-inflammatory cytokine genotype is linked negatively and positively,
      respectively, with life-span, because of its influence on inflammation.

PMID- 12496678
TI  - Microgravity as a model of ageing.
AB  - PURPOSE OF REVIEW: Longevity with good health and long-term survival in space are
      two of the many challenges that scientists face in the twenty-first century.
      Ageing and life in space are both associated with undesirable effects on normal
      physiological processes. This review will outline how the endocrine, metabolic,
      immune and musculoskeletal systems are affected by microgravity and ageing,
      drawing analogies between the observed changes in an attempt to highlight common
      mechanisms. RECENT FINDINGS: Mild hypothyroidism, increased stress hormones
      (mainly catecholamines), decreased sex steroids, insulin resistance, impaired
      anabolic response to food intake, anorexia, altered mitochondrial function and
      systemic inflammatory response are common features of both ageing and
      microgravity. Both conditions lead to progressive bone and muscle atrophy,
      compromising mobility and the ability to perform essential daily tasks. In
      skeletal muscle, both ageing and space flight lead to weakness from whole muscle
      to single fibre level, accompanied by marked alterations in muscle architecture
      and in tendon mechanical properties. SUMMARY: What makes microgravity an
      interesting and unique tool for gerontologists is that many space-related
      physiological changes resemble those observed during ageing, but are more or less
      quickly restored after re-entry, thus allowing the biology of ageing to be
      investigated both ways, not only during its development but also during recovery.

PMID- 12496679
TI  - Gastrointestinal diseases in the elderly.
AB  - PURPOSE OF REVIEW: The subject of gastrointestinal disorders in the elderly is
      timely and important because of the demographic reality that soon over 20% of our
      population will be older than 65 years of age, utilizing perhaps 50% of our total
      healthcare costs. The purpose of this review is to draw attention to some areas
      of clinical information that point in the direction of better clinical care for
      the elderly. Medicine is finally advancing from the era when most symptoms in
      older patients were ascribed to the aging process itself. Indeed, within
      gastroenterology there are few changes that occur inevitably as part of aging.
      RECENT FINDINGS: Progress has been made in several areas of gastrointestinal
      pathophysiology. These include: the pathophysiology of swallowing and evacuation
      disorders and the beginning of the application of techniques derived from
      physiological studies to improve function; recognizing the importance of reflux
      esophagitis and its complications and improving treatment; understanding the
      importance of disorders of malabsorption and their impact upon nutrition in the
      elderly; major issues in the diagnosis and management of inflammatory bowel
      disease in this age group; and approaches to the prevention and treatment of
      gastrointestinal cancer, particularly colorectal cancer. SUMMARY: As we pay more
      attention to these areas and encourage clinical research we expect to improve the
      treatment of older patients with these diseases and to reduce the burden of
      morbidity in this population.

PMID- 12496680
TI  - Gut changes attributed to ageing: effects on intestinal microflora.
AB  - PURPOSE OF REVIEW: There is increased evidence of several impaired
      gastrointestinal functions with ageing. In the elderly, however, most
      gastrointestinal functions remain relatively intact because of the large reserve
      capacity of the intestine and the great secretion capacity of the pancreas. This
      review will focus on changes in gut microflora observed in the elderly and on the
      potential benefit of probiotics in this population. RECENT FINDINGS: Recent
      studies suggest that age affects the intestinal microflora with a decrease in
      anaerobes and bifidobacteria population and an increase in enterobacteria. These
      changes and the reduced intestinal immunity of the aged may favour
      gastrointestinal infections that are frequent in the elderly. Clostridium
      difficile-associated diarrhoea, one of the most common nosocomial infections in
      the elderly, has a profound effect on morbidity, mortality and health costs.
      Probiotics may have interesting positive effects on intestinal function, and the
      efficacy of treatment with Lactobacilli and Saccharomyces boulardii in
      Clostridium difficile-associated diarrhoea has been well established in a recent
      meta-analysis. Studies performed in healthy elderly patients suggest that diet
      supplementation with probiotics may reduce the impaired immunity associated with
      ageing. SUMMARY: Important changes in intestinal microflora of the elderly have
      recently been demonstrated and may have important clinical consequences. Further
      studies should be conducted to determine if the consumption of probiotics is
      associated with a lower infection rate and a higher effectiveness of vaccines.

PMID- 12496681
TI  - Mechanisms of altered protein turnover in chronic diseases: a review of human
      kinetic studies.
AB  - PURPOSE OF REVIEW: Changes in hormone secretion, tissue perfusion, oxygen
      availability, energy-protein intake, free amino acid pattern, hydration state,
      acid-base balance as well as activation of the systemic inflammatory response may
      affect protein synthesis and degradation. The overall purpose of this review is
      to describe how these factors may interact to change protein turnover in the
      different directions seen in kinetic studies in humans. RECENT FINDINGS: Evidence
      indicates that, in vivo, changes of protein synthesis and degradation are
      strictly related. When protein synthesis is primarily suppressed, protein
      degradation is found to be unchanged or even slightly decreased. When protein
      degradation is primarily accelerated, the rate of synthesis is unchanged or even
      increased. Chronic disease states can, therefore, be characterized either by
      decreased or accelerated protein turnover. Apparent discrepancies among various
      studies in chronic uraemia, liver cirrhosis, chronic obstructive pulmonary
      disease and cancer may stem from the fact that the pathogenesis of protein
      metabolism abnormalities is multifactorial. When the effects of inflammatory
      mediators and stress hormones start overwhelming factors that tend to decrease
      protein synthesis and turnover (decreased protein-energy intake, physical
      activity, tissue oxygen delivery, leucine levels, etc.), the rate of protein
      degradation and turnover may increase. SUMMARY: Low-protein turnover conditions
      are usually associated with the adequate sparing of body proteins, whereas in
      high-protein turnover conditions protein loss may proceed at a faster rate.
      Nonetheless, impaired recovery from acute complications and the reduced renewal
      of damaged and toxic proteins are potential undesired consequences of low-protein
      turnover.

PMID- 12496682
TI  - Collagen turnover in bone diseases.
AB  - PURPOSE OF REVIEW: The primary aim of this review is to highlight recent advances
      in techniques available for assessing collagen turnover, particularly in relation
      to the diagnosis and management of bone disorders. As collagen is the major
      protein constituent of bone, its metabolites form the basis of most of the
      biochemical markers, but their efficacy needs to be viewed in the context of
      other non-collagenous markers, for which methodology is also advancing rapidly.
      RECENT FINDINGS: New markers of bone metabolism have been developed utilising the
      age-dependent isomerisation and racemisation of aspartyl residues at the C
      terminal end of collagen. These methods allow measurement of the ratio between
      newly synthesised and mature collagen: this ratio appears to provide a novel
      indicator of the fracture risk for osteoporosis. Other studies have led to an
      improved understanding of biological variability, particularly in relation to the
      effects of feeding. Bone resorption assays have been applied to a wide range of
      diseases and have been especially useful in monitoring the efficacy of novel
      therapies. SUMMARY: New assays have been developed to facilitate better
      monitoring of collagen metabolism in bone diseases. A more complete understanding
      of biological variability, particularly the effects of feeding, have led to
      improved clinical applicability of these assays in detecting disease and
      monitoring therapy. Part of the future challenge, however, is to ensure that
      commercial assay developments keep pace with clinical expectations.

PMID- 12496683
TI  - Altered amino acid metabolism in chronic obstructive pulmonary disease: new
      therapeutic perspective?
AB  - PURPOSE OF REVIEW: Wasting of muscle mass, commonly present in patients with
      chronic obstructive pulmonary disease, is a complex process involving changes in
      the control of intermediary metabolism as well as in muscle cell status. Although
      research exploring intermediary metabolism in chronic obstructive pulmonary
      disease is still in its infancy, there is an increased interest in a potential
      role for amino acids in modulating muscle anabolism. This review aims at
      summarizing and critically evaluating the available clinical studies examining
      alterations in amino acid profile in plasma and skeletal muscle of patients with
      chronic obstructive pulmonary disease. RECENT FINDINGS: All studies show
      pronounced alterations in plasma and muscle amino acid status in patients with
      chronic obstructive pulmonary disease but no consistent "disease specific"
      pattern for most amino acids. Variability is likely influenced by the
      heterogeneity of the disease with respect to lung function and nutritional state.
      Nevertheless, general consistency exists in chronic obstructive pulmonary disease
      with respect to (1) a reduced plasma branched-chain amino acid level, and (2) a
      decreased muscle glutamate concentration. Alterations in branched-chain amino
      acid metabolism appear to be influenced by the degree of muscle wasting, while
      the reduction in muscle glutamate is related to the diffusing capacity as a
      hallmark of emphysema. The reduction in glutamate status is associated with
      reduced muscle glutathione levels and appears to be linked to enhanced glycolysis
      as evidenced from an accelerated increase in plasma lactate during exercise.
      SUMMARY: Underlying mechanisms of the observed alterations in amino acid profile
      in chronic obstructive pulmonary disease, and the influences of disease
      associated mediators such as chronic low-grade inflammation and (chronic and
      intermittent) hypoxia are speculative and need to be explored in experimental
      study designs.

PMID- 12496684
TI  - Protein metabolism in liver cirrhosis: from albumin to muscle myofibrils.
AB  - PURPOSE OF REVIEW: Liver cirrhosis in the advanced state is characterized by
      protein wasting, as indicated by the loss of muscle mass, hypoalbuminemia, and an
      abnormal amino acid profile. The protein wasting condition cirrhosis is
      associated with a poor prognosis and reduced survival. Poor nutrition, metabolic
      and hormonal abnormalities, and other disease-associated alterations may all
      concur to protein wasting. An understanding of the causes and mechanisms leading
      to protein wasting in cirrhosis may help in the development of nutritional
      interventions and new therapies. RECENT FINDINGS: Albumin and muscle protein
      turnover in cirrhotic patients have been studied in vivo with the aid of isotope
      dilution techniques or organ catheterization. Albumin synthesis appears to
      parallel liver function, i.e. the more compromised is the liver, the less is the
      albumin production rate. Meal-induced albumin synthesis is impaired even in
      compensated cirrhotic patients. Skeletal muscle protein synthesis is diminished
      in cirrhosis, and total muscle protein breakdown also appears to be increased,
      thus explaining the reduced muscle mass. Either hormone or substrate resistance,
      or newly involved substances (cytokines, insulin-like growth factor 1, leptin)
      may play a role in the reduced synthesis of both albumin and muscle proteins in
      liver cirrhosis. SUMMARY: Abnormalities of both albumin and muscle protein
      turnover have been demonstrated in liver cirrhotic patients. The possible role of
      the multiple hormonal and metabolic abnormalities of this disease, as well that
      of cytokines and other recently discovered substances, need to be investigated
      further.

PMID- 12496685
TI  - Exercise treatment to counteract protein wasting of chronic diseases.
AB  - PURPOSE OF REVIEW: The objective is to summarize the findings from recent (June
      2001-2002) studies that have examined the potential benefits of exercise training
      for the treatment of wasting associated with sarcopenia, cancer, chronic renal
      insufficiency, rheumatoid arthritis, osteoarthritis and HIV. In many clinical
      conditions, protein wasting and unintentional weight loss are predictors of
      morbidity and mortality. The pathogenesis of protein wasting in these conditions
      can be different, but the fundamental mechanism is an imbalance between muscle
      protein synthetic and proteolytic processes. The muscle proteins most affected
      and the precise alterations in their synthetic and proteolytic rates that occur
      in each cachectic condition are still under investigation. RECENT FINDINGS:
      Regular exercise, or sometimes just a modest increase in physical activity, can
      mitigate muscle protein wasting. Aerobic exercise training primarily alters
      mitochondrial and cytosolic proteins (enzyme activities), while progressive
      resistance exercise training predominantly increases contractile protein mass.
      Previous studies indicate that resistance exercise acutely increases the muscle
      protein synthetic rate more than muscle proteolysis such that the muscle amino
      acid balance is increased for up to 2 days after exercise. Progressive resistance
      exercise training increases muscle protein synthesis and muscle mass, but
      attenuates the increment in proteolysis that results from a single bout of
      resistance exercise. The cellular mechanisms that produce these adaptations are
      not entirely clear. SUMMARY: In general, patients with wasting conditions who can
      and will comply with a proper exercise program gain muscle protein mass, strength
      and endurance, and, in some cases, are more capable of performing the activities
      of daily living.

PMID- 12496686
TI  - Protein turnover in atrophying muscle: from nutritional intervention to
      microarray expression analysis.
AB  - PURPOSE OF REVIEW: In response to decreased usage, skeletal muscle undergoes
      adaptive reductive remodeling due to the decrease in tension on the weight
      bearing components of the musculo-skeletal system. This response occurs with
      uncomplicated disuse (e.g. bed rest, space flight), as a secondary consequence of
      several widely prevalent chronic diseases for which activity is reduced (e.g.
      chronic obstructive pulmonary disease and chronic heart failure) and is part of
      the aging process. The problem is therefore one of considerable clinical
      importance. RECENT FINDINGS: The impaired function and exercise intolerance is
      related more to the associated muscle wasting rather than to the specific organ
      system primarily impacted by the disease. Progress has continued in describing
      the use of anabolic drugs and dietary manipulation. The major advance in the
      field has been: (i) the discovery of the atrogin-1 gene and (ii) the application
      of microarray expression analysis and proteomics with the objectives of obtaining
      comprehensive understanding of the pathways changed with disuse atrophy. SUMMARY:
      Disuse atrophy is a common clinical problem. There is a need for therapeutic
      interventions that do not involve exercise. A better understanding of the
      changes, particularly at the molecular level, could indicate hitherto unsuspected
      sites for nutritional and pharmacological intervention.

PMID- 12496687
TI  - Isotopic investigation of nitric oxide metabolism in disease.
AB  - PURPOSE OF REVIEW: Nitric oxide is an important mediator of both physiological
      and pathophysiological processes. Nitric oxide is produced during direct
      conversion of arginine to citrulline. Nitric oxide is rapidly metabolized, mainly
      to nitrite/nitrate, and finally excreted as urinary nitrate. For that reason,
      plasma and urinary nitrite/nitrate have been measured frequently as indicators of
      nitric oxide production, but it is becoming clear that these methods only give
      qualitative data. More recently, stable isotope methods have been introduced for
      quantitative measurement of nitric oxide production. This review aims at
      summarizing and evaluating these isotopic investigations of nitric oxide
      metabolism in disease. RECENT FINDINGS: Different stable isotope methods are used
      to measure whole body nitric oxide production in vivo. These methods are all
      based on infusion of guanidino-labeled L-arginine and subsequent measurement of
      labeled products (e.g. nitrite/nitrate or citrulline). Nitric oxide synthesis in
      healthy individuals is found to be in the range of 0.2-1.0 micromol kg h, only
      0.5-1% of arginine production. In diseased states, nitric oxide synthesis was
      found to be either decreased or increased. Increased nitric oxide synthesis was
      observed in gastroenteritis patients and in some animal models of sepsis. In
      patients with renal failure, however, both increased and decreased nitric oxide
      production have been reported. Nitric oxide production was not changed in
      familial hypercholesterolemia patients and after typhoid vaccination. SUMMARY:
      Using stable isotopes to measure whole body nitric oxide production in vivo is
      the most accurate method to study quantitative changes in the nitric oxide
      production rate. This technique is easy to perform in both healthy and diseased
      individuals, requiring infusion of stable isotopes for only a few hours and blood
      sampling.

PMID- 12496688
TI  - Early detection of cervical neoplasia: narrowing the cytohistologic divide.

PMID- 12496690
TI  - Symposium part 1: Should the Bethesda System terminology be used in diagnostic
      surgical pathology?: Point.
AB  - During the past 50 years, the histologic classification of cervical
      intraepithelial neoplasia (CIN) has evolved to incorporate the entire spectrum of
      genital papillomavirus infections, segregating those lesions with the higher risk
      of containing prototypic high-risk human papillomavirus types, and recently has
      meshed with treatment algorithms that include loop electrical excision procedures
      and follow-up alone. This review describes a classification system that divides
      CIN into categories of low-grade (CIN 1) and high-grade (CIN 2 and CIN 3). To
      successfully apply this system, the practitioner must efficiently exclude
      nonneoplastic entities and base the distinction of CIN 1 from CIN 2/3 on criteria
      that recognize the effects of viral oncogenes on replicating cells. This is
      achieved by basing the diagnosis of CIN 1 on uniform polarized epithelial growth,
      low mitotic index, low mitotic counts, and minimal parabasal cell anisokaryosis
      and coarse chromatin and CIN 2 on the presence of these features or abnormal
      mitoses. Simply put, the definition of CIN 2 (or higher) is the presence of
      atypical immature cells in the biopsy that if seen in a cytologic smear would
      merit a diagnosis of high-grade squamous intraepithelial lesion. In essence, a
      successful two-grade system requires careful application of cytologic criteria in
      a histologic milieu. This model is illustrated in a set of 25 images that
      underscore the importance of excluding benign changes (with the appropriate use
      of biomarkers), segregating unusual variants of low-grade squamous
      intraepithelial lesions, and identifying the morphologic transition to high-grade
      squamous intraepithelial lesions (CIN 2 or CIN 3) with an acceptable level of
      reproducibility.

PMID- 12496691
TI  - Symposium part 2: Should the Bethesda System terminology be used in diagnostic
      surgical pathology?: Counterpoint.
AB  - The criteria currently used for grading cervical intraepithelial neoplasia (CIN)
      are arbitrary and subjective with consequent considerable intra- and
      interobserver variability. None of the currently used criteria make a clear-cut
      case for changing terminology. The combination of CIN 2 and CIN 3 into a high
      grade lesion is not supported by biologic behavior or HPV typing and leads to
      overtreatment. The various shifts in nomenclature over the last 50 years through
      the dysplasia, CIN, and Bethesda systems, although intellectually stimulating,
      have neither improved diagnostic accuracy nor patient management. On the
      contrary, they often caused confusion and duplication, leading to the common and
      ironic practice that several terminologies are now being used in an additive
      fashion. New diagnostic markers are on the horizon as a result of the rapid
      development in the areas of genomics and proteomics. It seems likely that
      specific molecular biomarkers will become available, allowing the consistent and
      accurate discrimination between those intraepithelial lesions that will
      ultimately become invasive from the vast majority of lesions that will regress or
      persist. It is preferable at this time to maintain the current three-tier system,
      which is well entrenched and accepted around the world, until a novel approach
      places the classification of cervical precursor lesions on a new and solid
      footing. Ideally, we will then have a single-tier system identifying reliably
      those lesions that have the potential to become invasive.

PMID- 12496692
TI  - Symposium part 3: Should pathologists diagnose endocervical preneoplastic lesions
      "less than" adenocarcinoma in situ?: Point.
AB  - The insufficient state of knowledge concerning the biology of endocervical
      glandular lesions is compounded by the lack of universal diagnostic criteria for
      recognizing endocervical glandular dysplasia. This study addressed the issue of
      diagnostic reproducibility of noninvasive endocervical glandular lesions and
      tested the proposed new scoring scheme designed to improve this reproducibility.
      We have shown that the application of this scheme has significantly improved
      interobserver agreement in all diagnostic categories. Moreover, the results of
      this study lend support to the recommendation not to diagnose endocervical
      glandular dysplasia in the clinical setting, although this category can be still
      reliably separated out for research purposes. Application of our scoring scheme
      will bring uniformity to the diagnosis of noninvasive endocervical glandular
      lesions and allow the study of a precursor to endocervical adenocarcinoma

PMID- 12496693
TI  - Symposium part 4: Should pathologists diagnose endocervical preneoplastic lesions
      "less than" adenocarcinoma in situ?: Counterpoint.
AB  - Adenocarcinoma in situ (AIS) is the acknowledged precursor to most cases of
      invasive adenocarcinoma of the cervix. However, diagnostic terminology for
      lesions that do not fulfill all of the published criteria for AIS has not been
      standardized. Some have used the terms "glandular dysplasia" or " atypical
      hyperplasia" for purported antecedents of AIS, whereas others have adopted the
      term "cervical intraepithelial glandular neoplasia" (CIGN) for the entire
      spectrum of endocervical atypicality including AIS, with subcategories of "low
      grade" and "high-grade" CIGN. In this article the appropriateness of using these
      terms in diagnostic reports (versus the use of AIS to include some or most of the
      lesions encompassed by them, with nonspecific terminology for the remainder) is
      examined in the light of the relevant objective studies bearing on this question.
      An opinion is offered favoring the latter approach.

PMID- 12496694
TI  - Serous tumors of the ovary (borderline tumors and carcinomas) with and without
      micropapillary features.

PMID- 12496695
TI  - Advanced-stage serous borderline tumors of the ovary: a clinicopathological study
      of 49 cases.
AB  - There is controversy about patient outcomes and pathological parameters of
      prognostic significance in patients with stage II or stage III ovarian serous
      borderline tumors. Forty-nine cases of stage II and III ovarian serous borderline
      tumors were identified on review of the medical records at Vancouver Hospital and
      British Columbia Cancer Agency for the period from 1979 to 1996. Pathological
      features assessed included presence of micropapillary architecture, tumor cell
      DNA content (ploidy), and characteristics of the extraovarian implants, including
      invasiveness and mitotic activity. Clinical follow-up information (3-17 years of
      follow-up) was obtained for 48 patients. Fifteen patients had stage II tumors and
      34 had stage III tumors. Fourteen patients experienced tumor recurrence 1 to 8
      (mean 3.5) years after presentation and of these, six patients died of disease
      (2, 3, 4, 7, 10, and 11 years after presentation). Patients with gross residual
      disease, as assessed by the surgeon, more frequently experienced a recurrence
      compared with patients without gross residual disease, but this difference did
      not reach statistical significance (0.05<p<0.1). The patients who died of disease
      all had stage III tumors. Patients with invasive implants had a significantly
      worse outcome than patients with noninvasive implants (p<0.005). Other
      pathological features (ploidy, micropapillary architecture, invasiveness of
      implants, mitotic activity of implants) were not significantly predictive of
      tumor recurrence or death. No single pathological feature or combination of
      features was present in all patients who subsequently died of disease. In
      conclusion, the prognosis for patients with advanced-stage serous borderline
      tumors in this population-based study is very favorable, with only six patients
      ultimately dying of progressive disease. The combination of stage (stage III) and
      invasiveness of extraovarian implants identifies a small subset of patients with
      advanced-stage serous borderline tumors with a significantly worse prognosis, who
      may benefit from adjuvant therapy.

PMID- 12496696
TI  - Mutational analysis of K-ras segregates ovarian serous carcinomas into two types:
      invasive MPSC (low-grade tumor) and conventional serous carcinoma (high-grade
      tumor).
AB  - We previously proposed a dualistic model for ovarian serous carcinogenesis. One
      pathway involves the stepwise development of invasive micropapillary serous
      carcinoma (MPSC) from serous borderline tumor (atypical proliferative serous
      tumor) to noninvasive and then invasive MPSC. The carcinomas that develop in this
      fashion are characterized by low-grade nuclei and frequent K-ras mutations. They
      generally pursue an indolent course. In the other pathway conventional serous
      carcinoma (CSC) develops from the ovarian surface epithelium without what appears
      to be intermediate stages. These tumors display high-grade nuclei, wild-type K
      ras, and are very aggressive. Some of these CSCs display micropapillary
      architecture and simulate invasive MPSCs. This raises the possibility that these
      CSCs develop from an invasive MPSC. To address this question we reviewed 31
      moderately and poorly differentiated CSCs and identified 7 with morphological
      features of invasive MPSC. These seven tumors exhibited micropapillary
      architecture in at least 25% of the tumor but contained high-grade nuclei. The 31
      tumors were assessed for K-ras mutations using digital polymerase chain reaction
      based analysis. Despite their micropapillary architecture, all 7 CSCs with
      micropapillary features contained wild-type K-ras as did the other 24 pure CSCs.
      The results indicate that CSCs with micropapillary features are not derived from
      invasive MPSCs. The molecular findings also support the view that ovarian serous
      carcinomas should be graded as low- and high-grade tumors.

PMID- 12496697
TI  - Ovarian mucinous and mixed epithelial carcinomas of mullerian (endocervical-like)
      type: a clinicopathologic analysis of four cases of an uncommon variant
      associated with endometriosis.
AB  - The epithelial cells of ovarian mucinous carcinomas may sometimes appear similar
      to those of gastrointestinal or endocervical mucinous carcinomas, but most are
      composed of cells that do not suggest any particular derivation. We report four
      cases of mucinous ovarian carcinoma in which the cells were entirely or almost
      entirely endocervical-like. The patients' ages were 34, 43, 44, and 50 years. Two
      patients had bilateral tumors confined to the ovaries at initial staging; both
      also had synchronous endometrial carcinomas of the mucinous type. The two other
      patients had unilateral tumors, both with invasive metastases in the pelvis and
      abdomen at initial staging. In one of the latter cases a mullerian (endocervical
      like) mucinous borderline tumor (MMBT) of the opposite ovary had been removed 5
      years earlier, and in this case and two other cases the ovarian carcinomas had
      foci resembling MMBT, suggesting that they may be an invasive counterpart to
      these tumors. The six tumors ranged from 4 to 19 cm; five were grossly cystic
      with papillary or solid areas, and one was entirely solid. They were composed of
      closely packed glands, cysts, and cysts containing complex papillae. There was
      abundant intraglandular and intracystic mucin. The epithelial cells were well
      differentiated with infrequent mitoses and most were tall with mucinous cytoplasm
      resembling normal endocervical glandular cells. In three tumors there also were
      round to polygonal cells with eosinophilic cytoplasm; endometrioid foci were
      present in three tumors and a squamous focus was present in one. One tumor had a
      focally infiltrative growth pattern with a desmoplastic stromal reaction; the
      remaining five tumors had an exclusively confluent (expansile) pattern of
      invasion. Endometriosis was present in residual ovarian tissue adjacent to four
      tumors in three patients and had marked epithelial proliferation in three. All
      patients were treated postoperatively with chemotherapy and were without clinical
      recurrence with follow-up intervals of 8 months, 1.2 years, 2.9 years, and 3.8
      years. By immunohistochemical analysis the neoplastic epithelium was positive for
      estrogen and progesterone receptor proteins, vimentin, and cytokeratin 7, and
      negative or only focally positive for carcinoembryonic antigen and cytokeratin
      20, a profile that differs from that of the usual mucinous ovarian carcinoma and
      is supportive of a mullerian derivation. As with MMBTs, there was a strong
      association with endometriosis, and these tumors likely arise from endometriosis,
      possibly through an MMBT precursor in some cases. To better understand their
      clinicopathologic features and pathogenesis, this uncommon variant should be
      separated from the usual type in future studies of mucinous carcinomas of the
      ovary.

PMID- 12496698
TI  - Prognostic value of histologic grading of ovarian carcinomas.
AB  - Histologic grading of ovarian carcinomas has prognostic and therapeutic
      relevance, but although several grading systems have been proposed, no universal
      grading system has been established. Silverberg's group has recently proposed a
      simple histologic grading system of ovarian carcinomas. We studied its prognostic
      value in 70 patients with invasive ovarian carcinomas and compared it with that
      of histologic typing and clinical staging. Kaplan-Meier survival curves showed
      the following 5-year survival rate using the Silverberg grading system: grade I
      (n=21) 91%, grade II (n=20) 64%, grade III (n=29) 38% (p<0.001). Multivariate
      analysis indicated that the histologic grade, the clinical stage, and clear cell
      histologic type were significant prognostic factors. The Silverberg histologic
      grade correlated well with prognosis for all histologic types of ovarian
      carcinomas except for clear cell carcinoma. It is simple, reproducible, and
      provides useful prognostic information.

PMID- 12496699
TI  - Pseudoepitheliomatous hyperplasia in lichen sclerosus of the vulva.
AB  - Small tentacles or separated nests of squamous cells in the dermis are not
      uncommonly seen in long-standing vulvar lichen sclerosus (LS) associated with
      epidermal thickening. We recently encountered a case where separated nests of
      well-differentiated squamous cells in the dermis were difficult to distinguish
      from squamous cell carcinoma (SCC). Further biopsies showed similar nests
      originating from every hair follicle. We postulated a diagnosis of multifocal
      pseudoepitheliomatous hyperplasia (PEH) to explain this phenomenon. Because we
      could find no reference to PEH in the setting of LS, we reviewed the biopsies of
      92 women with extragenital and vulvar LS with and without carcinoma to determine
      its frequency and histological appearance. The study population, which excluded
      the index case, comprised 10 women with extra-anogenital LS, 58 with vulvar LS
      without carcinoma, and 24 with vulvar LS with carcinoma. The presence of PEH,
      epidermal thickness, predominant dermal collagen change, degree of inflammation,
      and presence of fibrin and red blood cells were recorded. The presence or absence
      of lichen simplex chronicus (LSC), squamous cell hyperplasia (SCH), and
      differentiated vulvar intraepithelial neoplasia (VIN) were recorded. PEH was
      identified only in vulvar LS, where it was seen in 7/58 (12.1%) women without
      carcinoma, 1/24 (8.3%) with carcinoma, and 0/10 (0%) with extra-anogenital LS.
      Two forms of PEH were seen: predominantly epidermal 7/8 (87.5%) and predominantly
      follicular 1/8 (12.5%). PEH was associated with increased epidermal thickness,
      less dermal edema, more dermal inflammation, fresh fibrin, and red blood cell
      extravasation. In all cases, there was associated LSC, but there was no SCH or
      differentiated VIN. In conclusion, PEH may explain many of the cases of dermal
      tentacles and separated squamous nests in vulvar LS with LSC. The association
      with fresh fibrin and red blood cells suggests that PEH might be a reaction to
      tissue damage. PEH is distinguished from SCC by its lack of atypia, confinement
      to the abnormal collagen, and limited growth. The pathologist must be careful
      about making a diagnosis of PEH in LS with epidermal thickening, looking
      carefully for basal atypia and other features of differentiated VIN in the
      overlying epidermis or dermal proliferation. We do not know whether PEH occurs in
      differentiated VIN and, if it does, how it could be distinguished from SCC.

PMID- 12496700
TI  - Expression of e-cadherin and beta-catenin in trophoblastic tissue in normal and
      pathological pregnancies.
AB  - E-cadherin and beta-catenin are cell-cell adhesion molecules, which are thought
      to play an important role in trophoblastic differentiation and remodelling during
      gestation. Their expression may be altered in pathological conditions with
      trophoblastic invasion. In this study, we used immunohistochemical methods to
      study the pattern of expression of E-cadherin and beta-catenin in villous
      trophoblastic tissue in normal and pathological pregnancies. In villous
      trophoblastic tissue, E-cadherin had a membranous distribution, whereas beta
      catenin had a mixed-membranous and granular cytoplasmic distribution. The levels
      of expression of E-cadherin and beta-catenin correlated with each other. From
      first to third trimesters, the expression of both E-cadherin and beta-catenin
      showed a decreasing trend. In preeclampsia, there was an up-regulation of E
      cadherin and beta-catenin expression. In placenta accreta, the level of
      expression of both did not differ from that in normal third-trimester placenta.
      In gestational trophoblastic diseases, there was a general trend of down
      regulation of both E-cadherin and beta-catenin. Altered expression of E-cadherin
      and beta-catenin may play a role in the development of normal and pathological
      placentas.

PMID- 12496701
TI  - The prognostic value of nuclear grading and the revised FIGO grading of
      endometrial adenocarcinoma.
AB  - The purpose of this study was to determine a convenient method for the
      modification of architectural grade by nuclear features and to evaluate the
      prognostic significance of the new International Federation of Gynecology and
      Obstetrics (FIGO) grading system by studying 288 patients with endometrioid
      endometrial carcinoma. All patients were subjected to initial surgical
      exploration and staging by 1988 FIGO guidelines. Three different grading systems
      were evaluated for their prognostic value: architectural, nuclear, and FIGO
      combined systems. All three grading systems significantly predicted poor
      survival, but only the FIGO grade (p < 0.001), stage (p < 0.001), and cervical
      involvement (p = 0.04) remained significant in multivariate analysis. In the
      architectural grade 2 group, the 5-year survival rate for 39 patients with grade
      1 or 2 nuclei was 87%, compared with 66% for 35 patients with grade 3 nuclei (p =
      0.03). In the architectural grade 1 group, the 5-year survival rate for 84
      patients with grade 2 nuclei was 93% without significant difference from the
      original group (96%). FIGO grade 3 tumor predicted 70% of deaths (29/41), whereas
      architectural grade 3 tumor detected 41% (17/41) of deaths (p = 0.001). In
      conclusion, in determining the FIGO grade, upgrading of architectural grade 1 or
      2 tumors by grade 3 nuclei was the most reliable method. The new FIGO grading
      system was prognostically superior to the previously used architectural grading
      system.

PMID- 12496702
TI  - Evaluation of the relationship between adenosarcoma and carcinosarcoma and a
      hypothesis of the histogenesis of uterine sarcomas.
AB  - The terminology of uterine sarcomas is confusing and has been inconsistently
      applied. The relationships among the various types of uterine sarcomas are
      unknown. To elucidate the relationship between carcinosarcoma (malignant
      mullerian mixed tumor) and adenosarcoma, a series of 26 consecutive endometrial
      carcinosarcomas was evaluated for the presence of an adenosarcoma-like component.
      Four of 26 carcinosarcomas (15%) had an adenosarcoma-like component. The clinical
      and pathologic features of these tumors were otherwise similar to ordinary
      endometrial carcinosarcomas. A histogenetic schema for uterine sarcomas is
      proposed, interrelating endometrial stromal sarcomas, adenosarcomas with and
      without sarcomatous overgrowth, and poorly differentiated sarcoma not otherwise
      specified. Although most carcinosarcomas are accepted as being metaplastic or
      sarcomatoid carcinomas, it is suggested that the carcinomatous component of 8% to
      16% of carcinosarcomas arise within, or in the endometrium adjacent to, an
      adenosarcoma. This latter group is then integrated into the histogenetic schema.
      Observations based on our data and the limited data in the literature that
      support this hypothesis include: 13% of endometrial carcinosarcomas have gross
      and microscopic features of collision tumors, 13% have an adenosarcoma-like
      component, 16% have a low-grade stroma, and approximately 8% are biclonal
      indicative of a collision tumor. The most parsimonious interpretation of these
      data indicates that approximately 8% to 16% of endometrial carcinosarcomas arise
      because of malignant transformation of the epithelial component within, or in the
      endometrium adjacent to an adenosarcoma.

PMID- 12496703
TI  - Analysis of p53 and c-erbB-2 expression in ovarian endometrioid carcinomas
      arising in endometriosis.
AB  - We assessed the immunohistochemical expression of p53 and c-erbB-2 oncoproteins
      in 13 ovarian endometrioid adenocarcinomas arising from endometriosis (group 1)
      and compared the findings with 15 otherwise similar cases without associated
      endometriosis (group 2). Tumors in group 1 showed a higher expression of both p53
      and c-erbB-2 (p = 0.015 and p = 0.048, respectively). The expression of the two
      proteins was also significantly associated in group 1 (p = 0.013) but not in
      group 2 (p = 0.63) tumors. The different pattern of expression of p53 and c-erbB
      2 in the two groups suggests that different molecular pathways may be involved in
      their pathogenesis.

PMID- 12496704
TI  - Uterine carcinosarcoma with complete sarcomatous overgrowth mimicking pure
      embryonal rhabdomyosarcoma.
AB  - A polypoid endometrial tumor arising in an 89-year-old woman was composed of pure
      embryonal rhabdomyosarcoma, whereas the metastatic tumor in the pelvic lymph
      nodes was entirely adenocarcinomatous. This finding indicates that some
      rhabdomyosarcomas of the uterus represent carcinosarcomas with extensive or total
      overgrowth by the sarcomatous component.

PMID- 12496705
TI  - Sebaceous carcinoma of the uterine cervix: a case report.
AB  - Sebaceous carcinoma is an uncommon neoplasm that usually arises in the head and
      neck region. A few cases of sebaceous carcinoma of the female genital tract have
      been reported, most of which arose in the vulva. We report the first case of
      sebaceous carcinoma of the uterine cervix. A 25-year-old, nulligravida woman
      presented with genital bleeding; there was a history of systemic lupus
      erythematosus but not Fordyce's disease. A 3.8-cm exophytic lesion on the cervix
      was biopsied and staged FIGO stage IB1. A radical hysterectomy was performed. On
      pathological examination, the tumor replaced the entire cervix and extended into
      the left parametrium and posterior vaginal fornix. On microscopic examination,
      the tumor was a sebaceous carcinoma, similar to those described in other sites.
      Postoperative radiotherapy was administered, but the patient died of tumor 8
      months postoperatively.

PMID- 12496706
TI  - History of gynecologic pathology: XIII. Dr. James W. Reagan.

PMID- 12496707
TI  - Aurel Babes.

PMID- 12496708
TI  - Fritz Strauss, Peter Grunwald, and Arthur Hertig.

PMID- 12496709
TI  - Simple clefts, complex problems: reflections on glandular lesions of the uterine
      cervix.

PMID- 12496710
TI  - Peritoneal "melanosis".

PMID- 12496711
TI  - [Treatment of otitis "Avoid at all costs therapeutic escalation". Interview by C.
      Maunand].

PMID- 12496712
TI  - [Factors influencing the appropriation of clinical guidelines by physicians].
AB  - DEFINITION: Clinical guidelines (CG) constitute a means to facilitate the
      decision-making process, defining what is and is not appropriate in fields
      concerned with public health matters or unregulated practices. METHOD: A
      bibliographical review has been conducted on factors likely to influence
      physicians' compliance to CG. These factors involve physicians, the guidelines
      themselves and the actions taken to encourage their implementation. FACTORS
      RELATED TO PHYSICIANS: In physicians' attitudes, we find not only their
      propensity to ask for help, to admit mistakes and weakness, but also their wish
      for continuing medical education. Practicing in an establishment or group
      consulting offices enhances their awareness of CG. The use of CG and the
      consequences of their implementation, as well as legal or financial concerns,
      increase physicians' confidence in the benefits of CG for themselves and their
      patients. FACTORS RELATED TO GUIDELINES: Clinical guidelines should be issued by
      multi-professional groups, among which there should be recognized experts and day
      to-day specialists. Their access should be easy and their updating frequent. The
      adaptation to the individual conditions of local practices is essential. THE
      IMPORTANCE OF IMPLEMENTATION: Once established, an intensive dissemination and
      active appropriation policy should be enacted. On the other hand, it is unlikely
      that passively diffused and non-updated CG will be adopted by newly qualified or
      long-established physicians installed in routine practice. Account must also be
      taken of the nature of certain CG, considered restrictive or coercive, and the
      targeted physician's attitudes and practicing habits - which is still unusual in
      France.

PMID- 12496713
TI  - [Etanercept--infliximab switch in rheumatoid arthritis 14 out of 131 patients
      treated with anti TNFalpha].
AB  - OBJECTIVE: Patients with severe rheumatoid arthritis and resistant to at least
      three DMARDS can benefit from anti-TNFalpha (tumor necrosis factor) therapy. In
      some patients, because of inefficacy or adverse events, treatment with one of the
      two available TNFalpha drugs (etanercept and infliximab) must be stopped. In this
      study, we explored the results in efficacy and tolerance of switching from one
      anti-TNFalpha to the other. PATIENTS: Between August 1999 and January 2002, we
      administered one of the two anti TNFalpha drugs to 131 patients: 67 patients
      received infiximab and 64 etanercept. RESULTS: Among the 67 patients treated with
      infliximab, 17 patients had to stop treatment. In 8 of them (4 allergies, 2
      infections and 2 non responders) the switch from infliximab to etanercept was
      beneficial for 5 patients, 2 patients did not respond and 1 patient withdrew for
      personal reasons. Among the 64 patients treated with etanercept, 13 had to stop
      treatment. In 6 of them (2 adverse events, 4 failures) the switch from etanercept
      to infliximab was beneficial for 3 patients, 2 did not respond and 1 withdrew
      because of adverse events. CONCLUSION: In all, 14 patients with severe rheumatoid
      arthritis and treated by one of the two TNFalpha drugs (and in whom treatment was
      stopped because of adverse events or inefficacy) benefited from the switch to the
      other anti- TNFalpha, with excellent response in 8 out of 14 patients.

PMID- 12496714
TI  - [The therapeutic use of D9-tetrahydrocannabinol (dronabinol) in refractory
      neuropathic pain].
AB  - INTRODUCTION: Despite the recent discovery of the potential mechanisms underlying
      the analgesic effects of cannabis, few clinical studies have so far assessed its
      analgesic effects, notably in the treatment of chronic non-malignant pain. All
      the studies used administration of cannabis alone. The aim of this open, pilot,
      study was to assess the efficacy and side effect profile of oral dronabinol
      (tetrahydrocannabinol - THC) in the treatment of refractory neuropathic pain.
      METHODS: Seven patients (3 women/4 men), aged 60 +/- 14 years, suffering from
      chronic refractory neuropathic pain, received oral THC titrated to the maximum
      dose of 25 mg/day (mean dose: 15 +/- 6 mg), during an average of 55,4 days
      (range: 13-128). Various components of pain (continuous, paroxysmal and brush
      induced allodynia) were assessed using VAS scores. Health-related Quality of Life
      (HRQL) was evaluated using the Brief Pain Inventory, and the Hospital Anxiety and
      Depression scale was used to measure depression and anxiety. RESULTS: THC did not
      induce significant effect on the various pain, HRQL and anxiety and depression
      scores. Numerous side effects (notably sedation and asthenia) were observed in 5
      patients out of 7, requiring premature discontinuation of the drug in 3 patients.
      CONCLUSION: The present study did not reveal any significant efficacy of THC in a
      small cohort of patients with chronic refractory neuropathic pain, but underlined
      the unfavorable side effect profile of the drug. These results may partly relate
      to the fact that oral dronabinol exhibits a poor therapeutic ratio (efficacy at
      the price of side effects). The development of new and better tolerated
      cannabinoids is warranted.

PMID- 12496715
TI  - [Myeloid pseudo-splenomegaly in a patient with a myeloma].
AB  - INTRODUCTION: Lymphoproliferative syndromes are rarely complicated by medullar
      fibrosis simulating myeloid splenomegaly. OBSERVATION: We report an unusual case
      of an IgD myeloma revealed in a context of myeloid splenomegaly in a 37 year-old
      man, initially admitted for severe anaemia associated with a voluminous
      splenomegaly. COMMENTARIES: The occurrence of myeloid splenomegaly during myeloma
      is extremely rare and only 14 cases have been reported. In this context,
      myelofibrosis is secondary to plasmocyte invasion of the bone marrow and
      regresses, or disappears, following specific treatment of the myeloma. The
      hypothesis evoked to explain the appearance of a secondary myelofibrosis is the
      "inappropriate" secretion, by the malignant plasmocyte clone, of functional
      analogs of pro-fibrosis cytokines, usually secreted by the mega-caryocyte
      precursors implied in myeloid splenomegaly.

PMID- 12496716
TI  - [The use of drops and powders in the ears].

PMID- 12496717
TI  - [News on diabetes and public health perspectives].

PMID- 12496719
TI  - New techniques in training and education: simulator-based approaches to
      anesthesia and intensive care.

PMID- 12496718
TI  - [Efficacy and acceptability of rilmenidine in a population of 2 738 hypertensive
      diabetic patients].
AB  - CONTEXT: Despite the constant enrichment of the pharmacopoeia, the normalizing of
      blood pressure in hypertensive diabetic patients remains difficult. OBJECTIVE: To
      assess the efficacy and acceptability of rilmenidine in first intention in
      hypertensive diabetics. METHODS: In a population of 18 235 hypertensive patients,
      the sub-population of diabetic patients was followed-up in an open study over one
      year. These patients were initially treated with 1 mg/day of rilmenidine with the
      possibility of adapting the dose - increasing to 2 mg/d and association with a
      second or even third anti-hypertensor, left to the discretion of the physician -
      when the diastolic blood pressure remained strictly greater than 90 mmHg.
      RESULTS: The complete blood pressure data over a period of 12 months were
      obtained in 2 311 patients out of 2 738 (84.4%). After 12 months' treatment,
      75.9% of the 2 311 patients were normalized by the monotherapy with rilmenidine
      (diastolic blood pressure<90 mmHg according to the recommendations in force at
      the time of the study). The clinical acceptability was good and comparable to
      that obtained in the general population of 18 235 hypertensive patients. The
      biological parameters remained stable. CONCLUSION: This pharmaco-epidemiological
      assessment demonstrates, in conditions of current practice, the anti-hypertensive
      efficacy and acceptability of rilmenidine in hypertensive diabetics, therefore
      confirming its place in the therapeutic arsenal of these patients.

PMID- 12496720
TI  - Key points in resuscitation for major trauma.

PMID- 12496721
TI  - SIAARTI recommendations for the treatment of postoperative pain.

PMID- 12496722
TI  - Anesthesia in Italy in 2000: sciences and working practice.
AB  - BACKGROUND: To survey current anaesthesiology practice in Italy. METHODS: We
      submitted to 1260 Italian anaesthesiologists in 12 different regional places a
      structured form aimed at surveying their common work practice. Our sample
      consisted of anaesthesiologists, age 26-63, with 1-35 years of professional
      practice. We believe that our sample represents about 7-10% of Italian
      anaesthesiologists, reflecting a global number of 600,000 procedures performed
      during 2000. The results have been analyzed by an Excel spreadsheet and they are
      reported as mean of the percentage of use declared in the case of drugs, and as
      percentage of the responses in the case of procedure and monitoring systems used.
      Furthermore we divided our sample population according to two criteria: principal
      place of work (general operating rooms (OR), subspecialty ORs, ICU) and years of
      anaesthesiology practice (<5>). The results have been crossmatched within and
      between the subgroups. RESULTS: The survey showed a composite state of
      anaesthesia practice in Italy. The main differences are between the youngest and
      the oldest anaesthesiologists and between the anaesthesiologists working mainly
      in the ICU and in the ORs. CONCLUSIONS: Italian anaesthesia practice is still a
      very composite reality.

PMID- 12496723
TI  - [Experience with remifentanil in the ICU].
AB  - BACKGROUND: Analgesia and sedation are indispensable in patients admitted to
      intensive care for the following, principal reasons: to control their state of
      anxiety, induce amnesia, improve their adaptation to mechanical ventilation, make
      invasive manoeuvres tolerable. The purpose of the present retrospective analysis
      is to assess the effectiveness of remifentanil in a total of 1085 patients
      admitted to our Resuscitation and Intensive Care Department in 1997-2001.
      METHODS: A sample of 60 adults was taken from these patients. The group was
      homogeneous in terms of age (67.3+/-10.2 kg), weight (66.7+/-10.2 kg), duration
      of sedation (6.8+/-1.6 days) and index of gravity (SAPS 30.1+/-4.4). The patients
      were suffering from chronic obstructive bronchopneumopathy, subjected to
      mechanical ventilation and sedated with remifentanil. The sample was then
      compared with another 2 groups (homogeneous with the first) of 20 patients each,
      treated with propofol and midazolam as the only drug. Following an initial bolus
      of 2 mg/kg (+/-0.04) for propofol and 0.15 mg/kg (+/-0.03) for midazolam (no
      bolus for remifentanil), the doses of subsequent continuous infusion (initial
      doses in the case of remifentanil) were: 0.05 mcg/kg/m (+/-0.01) for
      remifentanil; 1 mg/kg/h (+/-0.04) for propofol; 0.03 mg/kg/h (+/-0.006) for
      midazolam. In order to assess the level and quality of sedation, 2 subjective
      evaluation scales (Ramsey score and the Sedation-Agitation Score: SAS) and one
      system of objective evaluation (Bispectral Index; BIS) were employed. The BIS is
      a direct measure of the effects of anaesthetics on the brain. It is represented
      by a single digit (between 100, state of arousal, and zero, EEG flat), derived
      statistically and empirically from the EEG. RESULTS: No significant differences
      were encountered as regards quality of sedation among the 3 groups but there was
      a significant difference in negative cardiovascular activity in patients treated
      with propofol (12% reduction in Cl, 13.8% reduction in SVR). A significant
      accumulation of the drug was observed in cases treated with midazolam, whereas
      there was no accumulation for remifentanil and propofol in relation to the
      duration of the infusion. CONCLUSIONS: Of the various sedation modalities
      employed, we prefer the one which uses remifentanil as the sole drug because a
      good level of sedation is obtained, there is no accumulation, little interference
      with cardiovascular parameters and lower costs in comparison with the others.

PMID- 12496724
TI  - Fibre-optic awake intubation for caesarean section in a parturient with predicted
      difficult airway.
AB  - Anaesthetic management of a parturient with predicted difficult airway presenting
      for caesarean section (CS) is not a straightforward decision: general anaesthesia
      should be avoided because intubation can be impossible and a "cannot intubate,
      cannot ventilate" scenario might ensue, on the other hand regional techniques can
      be unsuccessful or, though rarely, have complications that require emergency
      intubation. The case is presented of a primigravida admitted to hospital at 37
      weeks' gestation with hypertension, intrauterine growth retardation and
      oligohydramnios. After a few days' observation, it was decided to proceed with an
      elective CS. The preoperative airway examination revealed a poor mouth opening
      with an interdental distance of 20 mm and a Mallampati class IV. The patient was
      classified as a case of difficult intubation and the following anaesthetic
      options were considered: epidural anaesthesia, spinal anaesthesia and awake
      fibreoptic intubation followed by general anaesthesia. The pros and the cons of
      these techniques were explained to the patient and it was suggested that awake
      fibreoptic intubation was the safest option. The patient gave her consent, so an
      uneventful nasal awake fibreoptic intubation was carried out under local
      anaesthesia. This case report offers the opportunity to underline the risk to
      perform a central blockade in a parturient with predicted difficult intubation,
      arguing that the safest course of action is an awake fibrescopic intubation,
      besides some controversial points to safely perform awake fibreoptic intubation
      in obstetric patients are discussed.

PMID- 12496725
TI  - Monopharmacologic general anaesthesia with sevoflurane in paediatric patient with
      Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic disease caused by a loss of paternal
      genes located in chromosome 15. Children affected by this syndrome often have
      preterm delivery; during childhood the hallmarks are: severe infantile hypotonia
      and feeding problems. Afterward, neurologic manifestations, endocrine signs and
      dysmetabolic abnormalities are usually seen together with craniofacial
      manifestations and musculoskeletal abnormalities. Obesity causes sleep
      abnormalities including sleep apnea. The case we present is of a 5 year old child
      (CA) scheduled for strabismus surgery. The child has a lot of typical (PWS)
      signs. A number of anaesthesiologic problems are associated with (PWS). Some of
      them relate to obesity, others to facial dysmorphism. Moreover, the syndrome may
      give a prolonged and exaggerated response to every sedative drug. P.W.S. is also
      characterized by thermoregulatory disorders. Sleep apnea occurs often.
      Considering all these problems, we planned a monopharmacologic anaesthesiologic
      procedure using sevoflurane.

PMID- 12496727
TI  - Human ethology and evolutionary psychology. Special issue dedicated to the memory
      of Dr. Zdenek Klein.

PMID- 12496728
TI  - Laudatio: Zdenek Klein.

PMID- 12496731
TI  - Dynamic systems and inferential information processing in human communication.
AB  - Research in human communication on an ethological basis is almost obsolete. The
      reasons for this are manifold and lie partially in methodological problems
      connected to the observation and description of behavior, as well as the nature
      of human behavior itself. In this chapter, we present a new, non-intrusive,
      technical approach to the analysis of human non-verbal behavior, which could help
      to solve the problem of categorization that plagues the traditional approaches.
      We utilize evolutionary theory to propose a new theory-driven methodological
      approach to the 'multi-unit multi-channel modulation' problem of human nonverbal
      communication. Within this concept, communication is seen as context-dependent
      (the meaning of a signal is adapted to the situation), as a multi-channel and a
      multi-unit process (a string of many events interrelated in 'communicative' space
      and time), and as related to the function it serves. Such an approach can be
      utilized to successfully bridge the gap between evolutionary psychological
      research, which focuses on social cognition adaptations, and human ethology,
      which describes every day behavior in an objective, systematic way.

PMID- 12496732
TI  - Human mate guarding.
AB  - Long-term committed mating is a fundamental strategy in the human repertoire.
      Successful enactment of this strategy requires solving two related adaptive
      problems--fending off potential mate poachers and preventing a mates from
      defecting. Mate guarding adaptations evolved to solve these persistent problems.
      Those who failed in mate guarding risked suffering substantial reproductive costs
      ranging from genetic cuckoldry to reputational damage to the entire loss of a
      mate. Because the precise nature of the adaptive problems confronted differed
      historically for the sexes, men and women evolved corresponding differences in
      the underlying psychology of mate guarding. Men's mate guarding, relative to that
      of women's, is strongly triggered as a consequence of being mated to young and
      physically attractive women, being confronted by interested rivals who have
      superior economic resources or prospects, and having a mate who displays signs of
      sexual involvement with a rival. Women's mate guarding, relative to that of
      men's, is triggered as a consequence of being mated to men high in income and
      status striving, rivals who are more physically attractive, and having a partner
      who shows signs of emotional involvement with another woman. Behavioral output of
      mate guarding adaptations range from vigilance to violence.

PMID- 12496733
TI  - Darwinian psychiatry and the concept of mental disorder.
AB  - In this paper, we discuss the concept of mental disorder from the perspective of
      Darwinian psychiatry. Using this perspective does not resolve all of the
      quandaries which philosophers of medicine face when trying to provide a general
      definition of disease. However, it does take an important step toward clarifying
      why current methods of psychiatric diagnosis are criticizable and how clinicians
      can improve the identification of true mental disorders. According to Darwinian
      psychiatry, the validity of the conventional criteria of psychiatric morbidity is
      dependent on their association with functional impairment. Suffering, statistical
      deviance, and physical lesion are frequent correlates of mental disorders but, in
      absence of dysfunctional consequences, none of these criteria is sufficient for
      considering a psychological or behavioral condition as a psychiatric disorder.
      The Darwinian concept of mental disorder builds from two basic ideas: (1) the
      capacity to achieve biological goals is the best single attribute that
      characterizes mental health; and (2), the assessment of functional capacities
      cannot be properly made without consideration of the environment in which the
      individual lives. These two ideas reflect a concept of mental disorder that is
      both functional and ecological. A correct application of evolutionary knowledge
      should not necessarily lead to the conclusion that therapeutic intervention
      should be limited to conditions that jeopardize biological adaptation. Because
      one of the basic aims of medicine is to alleviate human suffering, an
      understanding of the evolutionary foundations of the concept of mental disorder
      should translate into more effective ways for promoting individual and social
      well-being, not into the search for natural laws determining what is
      therapeutically right or wrong.

PMID- 12496734
TI  - Psychopathology or adaptation? Genetic and evolutionary perspectives on
      individual differences and psychopathology.
AB  - A greater understanding of psychopathology will be found in the integration of
      genetic and evolutionary perspectives on adaptation and function. Evolutionary
      theory proposes that adaptive traits are reproduced more successfully than
      maladaptive ones. However, some traits, while contributing to fitness in the
      ancestral environment, may contribute to fitness no longer. This is known as
      mismatch theory. Evolutionarily informed research into various "pathologies" has
      yielded interesting results, some based on this theory. This paper serves to
      distinguish between genetic and evolutionary perspectives on psychopathology as
      well as to examine some recent research on the selective forces that may be
      implicated in psychopathy, anorexic behavior, and ADHD. We suggest that research
      into psychopathy in general would benefit from an evolutionary perspective and an
      examination of the assumptions behind past research.

PMID- 12496735
TI  - Marriage: an evolutionary perspective.
AB  - Marriage is universal, and pair bonding is found in other species too with highly
      dependent young. So marriage functions as a reproductive social arrangement that
      traditionally involved the extended family. The sexes are not identical in their
      biological contributions to children's survival, so they seek somewhat different
      attributes in a mate. Men seek a young, attractive, sexually faithful bride.
      Women seek a man who is older, taller, and (as in many other species) socially
      dominant. Both sexes prefer a kind, healthy, attractive, similar mate who is
      emotionally attached to them. A spouse who fails to maintain sufficiently high
      mate value is vulnerable to divorce. Infertility and sexual dissatisfaction
      predict divorce, as does death of a child, but the more children, the stabler the
      marriage. Cross-cultural data suggest that cruel or subdominant men (e.g., poor
      providers) and unfaithful women are prone to divorce. Marriages in which the wife
      dominates the husband in economic contributions, nonverbal behavior, and decision
      making tend to be less satisfying. In societies in which wives are economically
      independent of husbands, divorce rates are high. As women's economic power has
      risen with industrialization, divorce rates have climbed. Economic and fitness
      considerations also help explain cultural differences in polygyny, age at
      marriage, arranged marriage, concern with the bride's sexual chastity, and
      marriage ceremonies. Other factors also affect marital dynamics, such as state
      subsidies to families, the sex ratio, and influence of the couple's parents.

PMID- 12496736
TI  - (Evolutionary) Theories of warfare in preindustrial (foraging) societies.
AB  - I present an inventory of theories of war causation (and on the origin of war) in
      preindustrial (traditional, foraging, 'primitive', hunter-gatherer, band- and
      tribe-level) societies, with emphasis on the roles of natural selection, sexual
      selection and kin selection. Also the school of sociocultural evolution is
      briefly discussed.

PMID- 12496737
TI  - Sex hormones influence human cognitive pattern.
AB  - The major sex differences in cognitive skills are summarized, and the role of sex
      hormones in early organization and possible maintenance of these differences is
      discussed. Using animal models and human hormonal anomalies, a good case can be
      made that prenatal androgens strongly influence adult cognitive pattern, though
      the relation between baseline androgens and spatial ability, for example, need
      not be linear. Moreover, men and women remain sensitive to variation in hormonal
      state, as evidenced in the fluctuations in cognitive and motor performance across
      natural diurnal, menstrual and circannual rhythms. Evidence from administration
      of exogenous hormones in humans is more equivocal, though this field ultimately
      should yield useful information.

PMID- 12496738
TI  - Female mate value at a glance: relationship of waist-to-hip ratio to health,
      fecundity and attractiveness.
AB  - A fundamental assumption of adaptive explanations of female attractiveness is
      that bodily features that males judge as attractive reliably signal youthfulness,
      healthiness, and fertility or female mate value. One of the bodily features,
      waist-to-hip ratio (WHR), is a reliable indicator of a female's reproductive age,
      sex hormone profile, parity and risk for various diseases. Systematic variation
      in the size of WHR also systematically affects the judgment of female
      attractiveness, healthiness, and youthfulness. This article summarizes recent
      findings about the relationship between female's WHR and various factors
      affecting reproductive capability and risk for diseases. Research on the
      relationship between attractiveness and WHR is discussed in light of some
      methodological objections to previous research. Finally, cross-cultural and
      historical data are presented that suggest that the relationship between WHR and
      female attractiveness is not culture-specific and not inculcated by modern
      Western fashion dictates or media.

PMID- 12496739
TI  - The neural mechanisms of mate choice: a hypothesis.
AB  - Scientists have described many physical and behavioral traits in avian and
      mammalian species that evolved to attract mates. But the brain mechanisms by
      which conspecifics become attracted to these traits is unknown. This paper
      maintains that two aspects of mate choice evolved in tandem: 1) traits that
      evolved in the "display producer" to attract mates and, 2) corresponding neural
      mechanisms in the "display chooser" that enable them to become attracted to these
      display traits. Then it discusses our (in-progress) fMRI brain scanning project
      on human romantic attraction, what we believe is a developed form of "courtship
      attraction" common to avian and mammalian species as well as the primary neural
      mechanism underlying avian and mammalian mate choice. The paper hypothesizes that
      courtship attraction is associated with elevated levels of central dopamine and
      norepinephrine and decreased levels of central serotonin in reward pathways of
      the brain. It also proposes that courtship attraction is part of a triune brain
      system for mating, reproduction and parenting. 1)The sex drive evolved to
      motivate birds and mammals to court any conspecifics. 2) The attraction system
      evolved to enable individuals to discriminate among potential mating partners and
      focus courtship activities on particular individuals, thereby conserving mating
      time and energy. 3) The neural circuitry for attachment evolved to enable
      individuals to complete species-specific parental duties.

PMID- 12496740
TI  - Toward an evolutionary psychology of religiosity.
AB  - How can the evolution of religiosity be explained? To answer this question, we
      attempt to develop an understanding of the psychological domains underlying
      religious behaviour. We see four evolved domains, the sum and interaction of
      which constitute religiosity, namely: mysticism, ethics, myths and rituals. Even
      if the individual content, accents and implementations differ in each specific
      religion, they nevertheless derive from evolved Darwinian algorithms that are
      species-specific adaptations of homo sapiens. Mysticism. Intuitive ontologies are
      the basis for mystical experiences. Usually they serve to classify reality into
      animate and inanimate objects, animals or plants, for example. For a variety of
      psychological reasons, supernatural experiences result from a mixture of
      different ontological categories. Ethics. The basis for ethics lies in the social
      competency of human beings. Ethics is founded on the concept of social exchange
      ("social-contract algorithm") with its ideas about reciprocity, fairness,
      justice, cheater detection, in-group/out-group differentiation, etc. Myths. The
      basis for myths is the "language instinct". We interpret myths as the verbal
      expression of the cognitive content of those individual modules that constitute
      the belief system. Above all, myths document the experience and processing of
      contingency and thus help social bonding. Rituals. Rituals are based on the
      handicap principle. By making certain symbols and acts more expensive, they
      signal commitment for a reliable in-group morale. In conclusion, we argue that
      human religiosity emerges from a cognitive interaction between these four
      domains. Religiosity processes contingencies and enhances co-operation through
      social bonding, norm setting and cheater detection. It fulfils those functions
      for which the mental modules of its four domains have evolved so that we feel it
      appears to be justified to attribute to religiosity the evolutionary status of an
      adaptation.

PMID- 12496741
TI  - Comparative approaches in evolutionary psychology: molecular neuroscience meets
      the mind.
AB  - Evolutionary psychologists often overlook a wealth of information existing
      between the proximate genotypic level and the ultimate phenotypic level. This
      commonly ignored level of biological organization is the ongoing activity of
      neurobiological systems. In this paper, we extend our previous arguments
      concerning strategic weaknesses of evolutionary psychology by advocating a
      foundational view that focuses on similarities in brain, behavior, and various
      basic psychological features across mammalian species. Such an approach offers
      the potential to link the emerging discipline of evolutionary psychology to its
      parent scientific disciplines such as biochemistry, physiology, molecular
      genetics, developmental biology and the neuroscientific analysis of animal
      behavior. We detail an example of this through our impending work using gene
      microarray technology to characterize gene expression patterns in rats during
      aggressive and playful social interactions. Through a focus on functional
      homologies and the experimental analysis of conserved, subcortical emotional and
      motivational brain systems, neuroevolutionary psychobiology can reveal ancient
      features of the human mind that are still shared with other animals. Claims
      regarding evolved, uniquely human, psychological constructs should be constrained
      by the rigorous evidentiary standards that are routine in other sciences.

PMID- 12496742
TI  - More efficient clinical trials through use of scientific model-based statistical
      tests.

PMID- 12496743
TI  - Pharmacokinetic interaction between amprenavir and delavirdine: evidence of
      induced clearance by amprenavir.
AB  - OBJECTIVE: Our objective was to determine the pharmacokinetic interaction between
      amprenavir and delavirdine. METHODS: Healthy volunteers participated in 2 open
      label, 3-period, longitudinal studies. In the first study, 12 volunteers received
      a single dose of amprenavir, 1200 mg, alone and then again after 7 days of
      delavirdine, 600 mg twice daily. In the second study, another 12 subjects
      received amprenavir, 1200 mg twice daily, alone for 7 days. After a 7-day washout
      period, subjects received delavirdine, 600 mg twice daily, alone for 7 days
      followed by a combination with amprenavir, 600 mg twice daily, for another 7
      days. Amprenavir and delavirdine pharmacokinetics when given alone and in
      combination were compared. RESULTS: All 12 subjects completed the first study,
      and 11 subjects completed the second study. Delavirdine significantly increased
      the area under the curve (AUC) of single-dose amprenavir by 4-fold (P =.0001).
      Amprenavir, 600 mg twice daily, with delavirdine produced higher levels of
      amprenavir AUC, minimum concentration (C(min)), and maximum concentration
      (C(max)), by 30%, 90%, and 18%, respectively, than those of amprenavir, 1200 mg
      twice daily, alone (P <.05). In contrast, amprenavir decreased delavirdine AUC,
      C(min), and C(max) by 50%, 70%, and 30%, respectively (P <.005). CONCLUSIONS:
      Because of the inhibitory effect of delavirdine on the cytochrome P450 3A4
      mediated metabolism of amprenavir, the combination of a reduced dose of
      amprenavir, 600 mg twice daily, with delavirdine resulted in a higher amprenavir
      exposure than the standard dose of amprenavir, 1200 mg twice daily. However,
      amprenavir induced the clearance of delavirdine, resulting in a reduction in
      delavirdine exposure. Further clinical studies are needed to determine the
      appropriate dosing regimens for delavirdine and amprenavir during
      coadministration.

PMID- 12496744
TI  - Limited sampling model for the analysis of 5-fluorouracil pharmacokinetics in
      adjuvant chemotherapy for colorectal cancer.
AB  - BACKGROUND: Administration of 5-fluorouracil may be associated with life
      threatening toxicities, resulting from a reduced drug biotransformation to the
      inactive metabolite 5-fluoro-5,6-dihydrouracil. Patients with severe toxicities
      display significant alterations of 5-fluorouracil pharmacokinetics, the
      monitoring of which may be made easier by the availability of a limited sampling
      model (LSM). METHODS: LSMs for 5-fluorouracil and 5-fluoro-5,6-dihydrouracil
      therapeutic monitoring have been developed in 80 patients with colorectal cancer
      (training set) given 5-fluorouracil, 370 mg/m(2) per day as an intravenous bolus,
      plus leucovorin, 100 mg/m(2) per day, for 5 days every 4 weeks. Pharmacokinetic
      analysis was performed on plasma levels of 5-fluorouracil and 5-fluoro-5,6
      dihydrouracil obtained on day 1 of the first cycle of chemotherapy, and backward
      stepwise regression analysis was used to determine the optimal LSM on the basis
      of bias (percentage mean prediction error [MPE]) and precision (percentage root
      mean square prediction error [RMSE]). RESULTS: An optimal model based on 2 time
      points was obtained (percentage MPE = 1.99% +/- 1.41%; percentage RMSE = 12.70%
      +/- 1.27%), and the predicted area under the time versus plasma concentration
      curve (AUC) was calculated as follows: predicted AUC (h x microg/mL) = 0.119 x
      C(5) + 1.436 x C(45) + 2.066, in which C(5) and C(45) are plasma concentrations
      of 5-fluorouracil at 5 and 45 minutes after drug administration, respectively.
      The application of this algorithm to pharmacokinetic analysis of plasma levels of
      5-fluorouracil in 80 patients (test set) allowed a precise estimation of AUC
      (percentage MPE = -0.09% +/- 1.37%; percentage RMSE = 12.17% +/- 1.23%). The best
      LSM for 5-fluoro-5,6-dihydrouracil was characterized by a percentage MPE of 
      0.64% +/- 0.86% and a percentage RMSE of 7.64% +/- 0.81%, and the optimal
      sampling time points were 45 and 180 minutes. CONCLUSION: The current LSM allows
      a reliable assessment of drug exposure and improves the use of therapeutic drug
      monitoring for treatment optimization of 5-fluorouracil in patients with cancer.

PMID- 12496745
TI  - Population pharmacokinetic model for irinotecan and two of its metabolites, SN-38
      and SN-38 glucuronide.
AB  - OBJECTIVE: The objective of the study was to develop and validate a population
      pharmacokinetic model for irinotecan and 2 of its metabolites, SN-38 and SN-38
      glucuronide (SN-38G). METHODS: Plasma concentrations were obtained during and up
      to 48 hours after a 90-minute continuous intravenous infusion of irinotecan (100
      340 mg/m(2)) in 78 patients. Data splitting was used to create model-building and
      model-validation data sets. Pharmacokinetic parameter estimates were obtained by
      compartmental methods to describe the disposition of metabolites that are
      dependent on the disposition of the parent compound. Relationships between
      patient attributes and estimates of clearance (CL) and volume of the central
      compartment for irinotecan, as well as CL and volume of the central compartment
      adjusted for the fraction metabolized for SN-38 and SN-38G, were explored by use
      of generalized additive models and graphic analysis. Selected covariates were
      introduced into the final population model by stepwise additions or deletions
      with the likelihood ratio test. RESULTS: SN-38 and SN-38G were shown to be
      formation rate-limited and were characterized by first-order rate constants of
      formation and elimination. Two subpopulations of SN-38 disposition were
      identified, presumably because of differences in the fraction of metabolite
      formed from the parent compound. Estimated irinotecan CL (25.2 L/h) was similar
      to that determined in other studies. Age and performance status were found to be
      important predictors of irinotecan CL, whereas variability in systemic exposure
      to the active metabolite, SN-38, was predicted by sex and hepatic function.
      CONCLUSION: The validated population pharmacokinetic model describing the
      disposition of irinotecan and 2 of its metabolites should facilitate the design
      of future studies to elucidate the relative contributions of the parent compound
      and SN-38 to the pharmacologic and toxic effects of irinotecan therapy.

PMID- 12496746
TI  - Pharmacokinetics of high-dose oral calcitriol: results from a phase 1 trial of
      calcitriol and paclitaxel.
AB  - OBJECTIVES: The data reported are from a trial designed to determine, in patients
      with advanced cancer, the maximum tolerated dose and pharmacokinetics of
      calcitriol when administered with paclitaxel, an agent whose antitumor activity
      in in vitro and in vivo studies has been shown to be enhanced by calcitriol. An
      additional goal was to evaluate the relationship between calcitriol dose and
      hypercalcemia. METHODS: Calcitriol was given orally for 3 consecutive days each
      week, and paclitaxel (80 mg/m(2)) was given intravenously weekly. Thirty-six
      patients were treated in cohorts composed of 3 to 9 patients, at escalating dose
      levels of calcitriol. The starting dose of calcitriol was 4 microg for 3
      consecutive days each week, and the maximum dose administered was 38 microg for 3
      consecutive days each week. The preparation of calcitriol used in this trial was
      a commercially available caplet (0.5 microg per caplet). Serum calcitriol
      concentrations were measured by radioimmunoassay. Detailed assessments of
      calcitriol pharmacokinetics were performed in 26 patients. RESULTS: There was
      substantial interpatient variation in peak serum calcitriol concentrations
      (C(max)), time to reach C(max), and area under the concentration versus time
      curve (AUC). Serum calcitriol AUC was not proportional to calcitriol dose (P
      =.0014). AUC for the 24-hour period after calcitriol administration [AUC (0-24)]
      at 38 microg was only 4 times that at 4 microg, instead of the 9.5-fold increase
      expected for a proportional relationship. Calcitriol plasma concentrations of 600
      to 1440 pg/mL were achieved. No dose-limiting toxicity occurred in this trial.
      CONCLUSIONS: Despite variability in absorption, very high doses of calcitriol can
      be safely administered with paclitaxel. The high calcitriol serum concentrations
      achieved in this study approach those that, both in vitro and in vivo, potentiate
      the cytotoxicity of taxanes and platinum analogs.

PMID- 12496747
TI  - Population pharmacokinetics of tacrolimus in adult kidney transplant recipients.
AB  - OBJECTIVES: The aims of this study were to investigate the population
      pharmacokinetics of tacrolimus in adult kidney transplant recipients and to
      identify factors that explain variability. METHODS: Population analysis was
      performed on retrospective data from 70 patients who received oral tacrolimus
      twice daily. Morning blood trough concentrations were measured by liquid
      chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought
      for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the
      use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on
      these parameters were weight, age, gender, postoperative day, days of tacrolimus
      therapy, liver function tests, creatinine clearance, hematocrit fraction,
      corticosteroid dose, and potential interacting drugs. RESULTS: CL/F was greater
      in patients with abnormally low hematocrit fraction (data from 21 patients only),
      and it decreased with increasing days of therapy and AST concentrations (P <.01).
      Average parameter estimates were as follows: CL/F = 31.8 L/h (hematocrit <0.33),
      CL/F = 24.2 L/h (hematocrit >0.33), and V/F = 2080 L. Marked interindividual
      variability (42% to 111%) and residual random error (3.7 ng/mL) were observed. On
      the basis of the derived model, a patient with normal AST (20 U/L) or high AST
      (200 U/L) concentrations 7 days after commencement of therapy would require a
      tacrolimus dose of 4.6 mg or 4.0 mg, respectively, to achieve a steady-state
      trough concentration of 10 ng/mL. CONCLUSIONS: The population pharmacokinetics of
      tacrolimus in adult kidney transplant recipients showed wide variability. Thus it
      is not possible to use a standard tacrolimus dose as an empiric predictor of
      concentration in this population. An understanding of factors that influence the
      pharmacokinetics of tacrolimus may assist in drug dosage decisions.

PMID- 12496748
TI  - Population pharmacokinetic and pharmacodynamic modeling of propofol for long-term
      sedation in critically ill patients: a comparison between propofol 6% and
      propofol 1%.
AB  - OBJECTIVES: A population pharmacokinetic and pharmacodynamic model of propofol
      for long-term sedation in critically ill patients is described, because limited
      information is available in these patients. In the models the influence of time
      independent covariates, in particular, the propofol formulation (propofol 6%
      versus propofol 1%), and of time-dependent covariates was investigated. METHODS:
      Twenty critically ill, mechanically ventilated patients received propofol
      formulated as propofol 6% (n = 10) or propofol 1% (n = 10) during a 2- to 5-day
      period. The level of sedation was assessed with the Ramsay 6-point scale. The
      data from a short-term sedation study in 24 patients after cardiac surgery were
      included. Population pharmacokinetic and pharmacodynamic modeling was performed
      with NONMEM. RESULTS: The pharmacokinetics was adequately described by a 2
      compartment model. The propofol formulation was not a significant covariate for
      the pharmacokinetics, whereas serum triglyceride concentration (TG) and relative
      body temperature (T(c)) were significant covariates for elimination clearance
      (CL). The population pharmacokinetic parameters were as follows: CL = 2.2 + 0.27
      x T(c) - 0.049 x TG (mean, 2.1 L/min); volume of central compartment, 22.2 L; CL
      (distribution), 1.5 L/min; and volume of peripheral compartment, 168 L. The
      addition of other time-independent covariates (long-term versus short-term
      sedation study, as well as physiologic characteristics) or time-dependent
      covariates (duration of propofol infusion, additional midazolam rates, and
      hemodynamic parameters) to the model did not improve the quality of fit. For the
      pharmacodynamics, the probability that the sedation level was equal to, or more
      than, a specific score was described with the use of a sigmoid inverse logit of
      the maximal achievable probability model. The values for the inverse logit of the
      concentration causing half of the maximal effect for Ramsay sedation scores of 2
      through 6 were 0.13 +/- 0.09, 0.31 +/- 0.17, 0.56 +/- 0.24, 0.79 +/- 0.31, and
      1.78 +/- 0.65 mg/L, respectively (population mean +/- SE). Interindividual
      variability was high, with a coefficient of variation of 119% in the 50%
      effective concentration values. No covariates were identified. CONCLUSIONS: The
      population models in critically ill patients showed no differences in
      pharmacokinetics or pharmacodynamics between propofol 6% and propofol 1%. TG and
      T(c) appeared to be significant covariates for elimination clearance. For the
      pharmacodynamics, when propofol concentrations were between 0.75 and 1.5 mg/L,
      Ramsay sedation score 6 was most probable (40%-75%) and the probability for
      Ramsay sedation score 5 was 20% to 40%. Large pharmacodynamic variabilities were
      observed.

PMID- 12496749
TI  - Gemfibrozil greatly increases plasma concentrations of cerivastatin.
AB  - BACKGROUND: Concomitant use of gemfibrozil with statins, particularly with
      cerivastatin, increases the risk of rhabdomyolysis, but the mechanism of this
      potentially fatal drug interaction remains unclear. Our aim was to study the
      effect of gemfibrozil on cerivastatin pharmacokinetics. METHODS: In a randomized,
      double-blind crossover study, 10 healthy volunteers took 600 mg gemfibrozil or
      placebo twice daily for 3 days. On day 3, each subject ingested a single 0.3-mg
      dose of cerivastatin. Plasma concentrations of cerivastatin, its metabolites, and
      gemfibrozil were measured up to 24 hours. RESULTS: During gemfibrozil treatment,
      the area under the plasma concentration-time curve [AUC(0-infinity)] of parent
      cerivastatin was on average 559% (range, 138% to 995%; P =.0002) and the peak
      concentration in plasma was 307% (138% to 809%; P =.0019) of the corresponding
      values in the placebo phase. Gemfibrozil increased the AUC(0-infinity) of
      cerivastatin lactone, on average, to 440% (94% to 594%; P =.0024) and that of
      metabolite M-1 to 435% (216% to 802%; P =.0002) of the control (placebo) values,
      whereas the AUC(0-24) of metabolite M-23 was decreased to 22% (11% to 74%; P
      =.0017). CONCLUSIONS: Gemfibrozil greatly increases plasma concentrations of
      cerivastatin, cerivastatin lactone, and metabolite M-1, whereas the level of
      metabolite M-23 is markedly reduced by gemfibrozil. Gemfibrozil therefore
      inhibits the formation of M-23, which is thought to be dependent on CYP2C8. The
      increased exposure to cerivastatin in the presence of gemfibrozil may explain the
      high incidence of myopathy observed with this combination, although the role of
      pharmacodynamic interactions between these 2 agents cannot be excluded.

PMID- 12496750
TI  - Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in
      human liver.
AB  - BACKGROUND AND OBJECTIVES: Fibrates induce hepatic peroxisome proliferation and
      carcinogenesis in rodents by activating peroxisome proliferator-activated
      receptor alpha (PPAR(alpha)). There is no conclusive evidence that humans are
      unresponsive to peroxisome proliferation, and concern exists about the long-term
      safety of fibrate treatment. METHODS: In a university hospital setting, 48
      patients with uncomplicated gallstones and a serum level of low-density
      lipoprotein cholesterol greater than 130 mg/dL were randomly assigned to open
      label treatment with bezafibrate (400 mg/d), fenofibrate (200 mg/d), gemfibrozil
      (900 mg/d), or placebo for 8 weeks before elective cholecystectomy. Serum samples
      for lipid determinations were obtained at baseline and before surgery. A liver
      specimen was obtained at operation, and the relative levels of messenger
      ribonucleic acid (mRNA) for the wild and truncated forms of PPAR(alpha), acyl
      coenzyme A oxidase, liver carnitine palmitoyltransferase I, apolipoprotein A-I,
      and stearoyl coenzyme A desaturase were determined. RESULTS: Fenofibrate,
      bezafibrate, and gemfibrozil reduced plasma low-density lipoprotein cholesterol
      levels by 22% (P =.009), 14% (P =.042), and 11% (not significant), respectively.
      Plasma triglyceride levels decreased significantly (24%-36%; P <.05), whereas
      high-density lipoprotein cholesterol levels rose nonsignificantly after treatment
      with the 3 fibrates. Except for a 35% increase of apolipoprotein A-I mRNA after
      fenofibrate administration (P <.05), none of the individual fibrates induced
      significant changes in the mRNAs tested, although as a group they increased the
      mRNA for liver carnitine palmitoyltransferase I by 40%(P =.08; marginally
      significant). CONCLUSIONS: Fibrate administration to humans at pharmacologic
      doses able to activate PPAR(alpha) and to induce a hypolipidemic effect does not
      increase the hepatic expression of acyl coenzyme A oxidase, a well-known marker
      of peroxisome proliferation in rodents.

PMID- 12496751
TI  - Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance
      dose and metabolic clearance.
AB  - OBJECTIVE: Our objective was to determine the influence of cytochrome P450 (CYP)
      2C9 and CYP2C19 genetic polymorphisms on warfarin dose requirement and metabolic
      clearance. METHODS: The study population consisted of 93 Italian outpatients
      receiving long-term warfarin anticoagulant therapy (international normalized
      ratio values, 2-3), divided into 3 dose groups: low (<26.25 mg/wk; n = 37),
      medium (26.25-43.75 mg/wk; n = 32), and high (>43.75 mg/wk; n = 24). Steady-state
      unbound plasma concentrations of S- and R-warfarin were measured by HPLC and
      equilibrium dialysis, and corresponding unbound oral clearance (CL(free)) values
      were calculated. Allelic variants of CYP2C9 (CYP2C9(*)2 and CYP2C9(*)3) and
      CYP2C19 (CYP2C19(*)2) were identified by polymerase chain reaction, followed by
      restriction enzyme analysis. RESULTS: Fifty-four patients carried no CYP2C9
      mutated alleles ((*)1/(*)1), 31 carried one ((*)1/(*)2, n = 15; and (*)1/(*)3, n
      = 16), and 8 carried two ((*)2/(*)2, n = 2; (*)3/(*)3, n = 2; and (*)2/(*)3, n =
      4). Two subjects were homozygous and 19 were heterozygous for the CYP2C19(*)2
      allele variant. The frequencies of CYP2C9 mutated alleles were 72% in the low
      dose group, 36% in the medium-dose group, and 4% in the high-dose group; the
      corresponding mean S-warfarin CL(free) values were 307.5 mL/min, 480.3 mL/min,
      and 881.3 mL/min. The mean S-warfarin CL(free) values varied significantly among
      the CYP2C9 genotype groups (P <.0001), although most patients (72%) with no
      mutated alleles showed S-warfarin CL(free) values in the same range as those
      carrying mutated alleles (58-777 mL/min). No relationship was found between S
      warfarin CL(free) and CYP2C19 genotype or between R-warfarin CL(free) and either
      CYP2C9 or CYP2C19 genotype. CONCLUSION: CYP2C9 genetic polymorphisms markedly
      influence warfarin dose requirements and metabolic clearance of the S-warfarin
      enantiomer, although nongenetic factors may also contribute to their large
      interindividual variability.

PMID- 12496752
TI  - Flumazenil reduces midazolam-induced cognitive impairment without altering
      pharmacokinetics.
AB  - OBJECTIVES: Intravenous midazolam is used as an in vivo biomarker of hepatic
      cytochrome P450 (CYP) 3A activity. Midazolam is a central nervous system
      depressant and can produce cognitive impairment. The purpose of this study was 2
      fold: (1) to determine whether administration of intravenous flumazenil given
      before intravenous midazolam minimizes cognitive impairment and (2) to determine
      whether flumazenil pretreatment has an effect on midazolam pharmacokinetics
      during hepatic CYP3A phenotyping. METHODS: Eleven healthy subjects (8 men)
      received intravenous flumazenil (0.005 mg/kg) or placebo followed 7 minutes later
      by intravenous midazolam (0.025 mg/kg) in a randomized, double-blind crossover
      study. Plasma midazolam concentrations were obtained before dosing and at 5, 30,
      60, 120, 240, 300, and 360 minutes after dosing and were assayed by liquid
      chromatography-tandem mass spectrometry. Midazolam pharmacokinetics were
      determined by noncompartmental methods. The two 1-sided tests procedure was used
      to compare area under the curve (AUC) between study phases. Data were log
      transformed before analysis, and bioequivalence criteria were applied. Digit
      symbol substitution tests, performed before dosing and at 5, 30, 60, 120, 240,
      300, and 360 minutes after dosing, were used to measure cognition. General linear
      modeling was used to compare scores between study phases. RESULTS: Midazolam AUC
      extrapolated to infinity [AUC(0-infinity)] between phases was bioequivalent. The
      AUC ratio (flumazenil plus midazolam/midazolam) was 0.99, with a 90% confidence
      interval of 0.98 to 1.00. Statistically significant differences(P <or=.05) in
      digit symbol substitution test scores between phases were determined relative to
      time and a phase-by-time interaction. CONCLUSIONS: Flumazenil minimizes midazolam
      induced cognitive impairment without influencing midazolam pharmacokinetics.
      However, the risk of side effects (ie, panic attack) caused by flumazenil should
      be thoroughly considered before implementation of this drug combination during
      phenotyping in healthy subjects.

PMID- 12496753
TI  - Application of semisimultaneous midazolam administration for hepatic and
      intestinal cytochrome P450 3A phenotyping.
AB  - OBJECTIVES: Determination of hepatic and intestinal cytochrome P450 (CYP) 3A
      activity is important, because CYP3A substrates show substantial variability in
      plasma concentrations as a result of variations in both hepatic and intestinal
      metabolism. The goals of this study were (1) to determine whether the hepatic and
      intestinal extraction ratios (ER(H) and ER(G), respectively) of the CYP3A probe
      drug midazolam are different when determined after semisimultaneous
      administration, as compared with administration on separate occasions
      (traditional method), and (2) to evaluate the hepatic and intestinal metabolism
      of midazolam in the presence and absence of ketoconazole by the semisimultaneous
      method. METHODS: Midazolam pharmacokinetics was assessed in 12 healthy volunteers
      after administration of midazolam, 5 mg orally, followed at 6 hours by 2 mg given
      by intravenous infusion. Concentration-time data were fitted to a combined oral
      intravenous infusion model by nonlinear regression (semisimultaneous method).
      Data from the semisimultaneous method were compared with those obtained after
      individual midazolam doses, 1 week apart (traditional approach). The effect of
      ketoconazole on midazolam pharmacokinetics after semisimultaneous administration
      was also determined in 4 healthy volunteers. RESULTS: There were no significant
      differences in bioavailability (0.343 +/- 0.100 versus 0.343 +/- 0.094), ER(H)
      (0.269 +/- 0.064 versus 0.267 +/- 0.077), and ER(G) (0.534 +/- 0.135 versus 0.531
      +/- 0.124) between the traditional and semisimultaneous methods. As expected,
      ketoconazole markedly increased the mean bioavailability to 0.838 (2.4-fold), the
      mean ER(H) was decreased 3.7-fold, and the mean ER(G) was decreased 5.7-fold.
      CONCLUSIONS: Midazolam pharmacokinetic parameters that are specific to liver and
      intestinal metabolism were not different between the traditional and
      semisimultaneous methods. The semisimultaneous method also yielded expected
      marked changes in the parameters as a result of ketoconazole inhibition. Thus the
      semisimultaneous midazolam method appears to be a suitable approach to determine
      hepatic and intestinal CYP3A activity at baseline and with enzyme inhibition.

PMID- 12496754
TI  - Benzodiazepines and the risk of urinary incontinence in frail older persons
      living in the community.
AB  - OBJECTIVE: Urinary incontinence is a common problem among older persons living in
      different community settings. The multifactorial origin of urinary incontinence
      has been largely addressed, and many previous studies have identified several
      reversible factors associated with incontinence. The aim of this study was to
      estimate the risk of urinary incontinence associated with the use of oxidative or
      nonoxidative benzodiazepines. METHODS: We analyzed data from a large
      collaborative observational study group, the Italian Silver Network Home Care
      project, which collected data on patients admitted to home care programs (N =
      4583). A total of 22 home health agencies participated in the project, which
      evaluated the implementation of the Minimum Data Set for Home Care instrument.
      The main outcomes measure was the prevalence of urinary incontinence and the
      association with benzodiazepine use. RESULTS: A total of 1475 individuals (21% of
      patients aged 60-74 years and 38% aged >or=75 years) reported urinary
      incontinence. Users of benzodiazepines had an increased risk of urinary
      incontinence of nearly 45% (odds ratio [OR], 1.44; 95% confidence interval [CI],
      1.12-1.83). The risk seemed to be of greater magnitude for exposure to oxidative
      agents (adjusted OR, 1.47; 95% CI, 1.09-1.99) than to nonoxidative
      benzodiazepines (adjusted OR, 1.35; 95% CI, 0.93-1.96). Among the oxidative
      benzodiazepines, the effect mainly resulted from agents with a long elimination
      half-life (adjusted OR, 1.75; 95% CI, 1.13-2.72). CONCLUSIONS: The metabolic
      pathway of the benzodiazepines is a good predictor of urinary incontinence. In
      frail elderly patients, oxidative benzodiazepines are potentially more harmful
      than nonoxidative agents. Among oxidative benzodiazepines, the best ones seem to
      be those with a short elimination half-life.

PMID- 12496755
TI  - The impact of wording in "Dear doctor" letters and in black box labels.
AB  - OBJECTIVES: The Food and Drug Administration and pharmaceutical manufacturers use
      "Dear doctor" letters to alert physicians about drug safety. To determine how
      such warnings may be improved, we retrospectively examined how variations in the
      wording of one series of "Dear doctor" letters affected their impact on
      concomitant dispensing of cisapride (Propulsid; Janssen Pharmaceutica,
      Titusville, NJ) and several medications contraindicated for concomitant use.
      METHODS: Concomitant dispensing was defined as dispensing cisapride and a
      contraindicated medication on dates when the intended duration of the two
      dispensings overlapped on at least 1 day. Using outpatient pharmacy claims from a
      New England health insurer, we calculated a concomitant dispensing rate for each
      calendar month as the number of concomitant cisapride dispensings divided by the
      total number of cisapride dispensings. We grouped drugs contraindicated for
      concomitant use with cisapride as (1) explicitly named in the warnings, (2) only
      mentioned as examples of a drug class, or (3) only implied as drug class members.
      We used multivariate analysis to relate temporal changes in concomitant
      dispensing rates to type of warning (explicit, example, or implied), patient
      demographic characteristics, season, calendar year, and temporal relationship to
      the "Dear doctor" warnings. RESULTS: A highly publicized letter sent in June 1998
      was associated with a notable decline (58%) in the concomitant dispensing rate
      with explicitly contraindicated drugs but not in the concomitant dispensing of
      cisapride with the example or implied drugs. An earlier letter, which had been
      explicit but was accompanied by less publicity, had no measurable effect on this
      study's measure of coprescription, nor did a later letter that emphasized
      comorbidities. CONCLUSIONS: Explicit, well-publicized drug warnings can change
      prescriber behavior.

PMID- 12496756
TI  - Caution when lean body weight is used as a size descriptor for obese subjects.

PMID- 12496757
TI  - Mutations in SBDS are associated with Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome (SDS; OMIM 260400) is an autosomal recessive disorder
      with clinical features that include pancreatic exocrine insufficiency,
      hematological dysfunction and skeletal abnormalities. Here, we report
      identification of disease-associated mutations in an uncharacterized gene, SBDS,
      in the interval of 1.9 cM at 7q11 previously shown to be associated with the
      disease. We report that SBDS has a 1.6-kb transcript and encodes a predicted
      protein of 250 amino acids. A pseudogene copy (SBDSP) with 97% nucleotide
      sequence identity resides in a locally duplicated genomic segment of 305 kb. We
      found recurring mutations resulting from gene conversion in 89% of unrelated
      individuals with SDS (141 of 158), with 60% (95 of 158) carrying two converted
      alleles. Converted segments consistently included at least one of two pseudogene
      like sequence changes that result in protein truncation. SDBS is a member of a
      highly conserved protein family of unknown function with putative orthologs in
      diverse species including archaea and eukaryotes. Archaeal orthologs are located
      within highly conserved operons that include homologs of RNA-processing genes,
      suggesting that SDS may be caused by a deficiency in an aspect of RNA metabolism
      that is essential for development of the exocrine pancreas, hematopoiesis and
      chrondrogenesis.

PMID- 12496758
TI  - Human mitochondrial transcription factor B1 methylates ribosomal RNA at a
      conserved stem-loop.
AB  - Human mitochondrial transcription factor B1 (h-mtTFB1) has an unprecedented
      relationship to RNA methyltransferases. Here, we show that this protein
      methylates a conserved stem-loop in bacterial 16S rRNA and that the homologous
      sequence in the human mitochondrial 12S molecule is similarly modified. Thus, h
      mtTFB1 appears to be dual-function protein, acting both as a transcription factor
      and an rRNA-modification enzyme.

PMID- 12496759
TI  - Mutations in NR4A2 associated with familial Parkinson disease.
AB  - NR4A2, encoding a member of nuclear receptor superfamily, is essential for the
      differentiation of the nigral dopaminergic neurons. To determine whether NR4A2 is
      a susceptibility gene for Parkinson disease, we carried out genetic analyses in
      201 individuals affected with Parkinson disease and 221 age-matched unaffected
      controls. We identified two mutations in NR4A2 associated with Parkinson disease
      (-291Tdel and -245T-->G), which map to the first exon of NR4A2 and affect one
      allele in 10 of 107 individuals with familial Parkinson disease but not in any
      individuals with sporadic Parkinson disease (n = 94) or in unaffected controls (n
      = 221). The age at onset of disease and clinical features of these ten
      individuals were not different from those of individuals with typical Parkinson
      disease. The mutations resulted in a marked decrease in NR4A2 mRNA levels in
      transfected cell lines and in lymphocytes of affected individuals. Additionally,
      mutations in NR4A2 affect transcription of the gene encoding tyrosine
      hydroxylase. These data suggest that mutations in NR4A2 can cause dopaminergic
      dysfunction, associated with Parkinson disease.

PMID- 12496760
TI  - DNMT1 is required to maintain CpG methylation and aberrant gene silencing in
      human cancer cells.
AB  - Transcriptional silencing by CpG island methylation is a prevalent mechanism of
      tumor-suppressor gene suppression in cancers. Genetic experiments have defined
      the importance of the DNA methyltransferase Dnmt1 for the maintenance of
      methylation in mouse cells and its role in neoplasia. In human bladder cancer
      cells, selective depletion of DNMT1 with antisense inhibitors has been shown to
      induce demethylation and reactivation of the silenced tumor-suppressor gene
      CDKN2A. In contrast, targeted disruption of DNMT1 alleles in HCT116 human colon
      cancer cells produced clones that retained CpG island methylation and associated
      tumor-suppressor gene silencing, whereas HCT116 clones with inactivation of both
      DNMT1 and DNMT3B showed much lower levels of DNA methylation, suggesting that the
      two enzymes are highly cooperative. We used a combination of genetic (antisense
      and siRNA) and pharmacologic (5-aza-2'-deoxycytidine) inhibitors of DNA methyl
      transferases to study the contribution of the DNMT isotypes to cancer-cell
      methylation. Selective depletion of DNMT1 using either antisense or siRNA
      resulted in lower cellular maintenance methyltransferase activity, global and
      gene-specific demethylation and re-expression of tumor-suppressor genes in human
      cancer cells. Specific depletion of DNMT1 but not DNMT3A or DNMT3B markedly
      potentiated the ability of 5-aza-2'-deoxycytidine to reactivate silenced tumor
      suppressor genes, indicating that inhibition of DNMT1 function is the principal
      means by which 5-aza-2'-deoxycytidine reactivates genes. These results indicate
      that DNMT1 is necessary and sufficient to maintain global methylation and
      aberrant CpG island methylation in human cancer cells.

PMID- 12496761
TI  - Neural correlates of cross-modal binding.
AB  - Little is known about how the brain binds together signals from multiple sensory
      modalities to produce unified percepts of objects and events in the external
      world. Using event-related functional magnetic resonance imaging (fMRI) in
      humans, we measured transient brain responses to auditory/visual binding, as
      evidenced by a sound-induced change in visual motion perception. Identical
      auditory and visual stimuli were presented in all trials, but in some trials they
      were perceived to be bound together and in others they were perceived as unbound
      unimodal events. Cross-modal binding was associated with higher activity in
      multimodal areas, but lower activity in predominantly unimodal areas. This
      activation pattern suggests that a reciprocal and 'competitive' interaction
      between multimodal and unimodal areas underlies the perceptual interpretation of
      simultaneous signals from multiple sensory modalities.

PMID- 12496762
TI  - Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4
      signaling.
AB  - Communication between glial cells and neurons is emerging as a critical parameter
      of synaptic function. However, the molecular mechanisms underlying the ability of
      glial cells to modify synaptic structure and physiology are poorly understood.
      Here we describe a repulsive interaction that regulates postsynaptic morphology
      through the EphA4 receptor tyrosine kinase and its ligand ephrin-A3. EphA4 is
      enriched on dendritic spines of pyramidal neurons in the adult mouse hippocampus,
      and ephrin-A3 is localized on astrocytic processes that envelop spines.
      Activation of EphA4 by ephrin-A3 was found to induce spine retraction, whereas
      inhibiting ephrin/EphA4 interactions distorted spine shape and organization in
      hippocampal slices. Furthermore, spine irregularities in pyramidal neurons from
      EphA4 knockout mice and in slices transfected with kinase-inactive EphA4
      indicated that ephrin/EphA4 signaling is critical for spine morphology. Thus, our
      data support a model in which transient interactions between the ephrin-A3 ligand
      and the EphA4 receptor regulate the structure of excitatory synaptic connections
      through neuroglial cross-talk.

PMID- 12496763
TI  - Screening for gene function in chicken embryo using RNAi and electroporation.
AB  - In the postgenomic era the elucidation of the physiological function of genes has
      become the rate-limiting step in the quest to understand the development and
      function of living organisms. Gene functions cannot be determined by high
      throughput methods but require analysis in the context of the entire organism.
      This is particularly true in the developing vertebrate nervous system. Because of
      its easy accessibility in the egg, the chicken embryo has been the model of
      choice for developmental in vivo studies. However, its usefulness has been
      hampered by a lack of methods for genetic manipulation. Here we describe an
      approach that could compensate for this disadvantage. By combining gene silencing
      by dsRNA (through RNA interference, RNAi) with in ovo electroporation, we
      developed an efficient method to induce loss of gene function in vivo during the
      development of the chicken CNS. This method opens new possibilities for studying
      gene function not only by gain-of-function but also by loss-of-function
      approaches and therefore represents a new tool for functional genomics.

PMID- 12496765
TI  - Introduction.

PMID- 12496764
TI  - Fingerprinting the circulating repertoire of antibodies from cancer patients.
AB  - Recognition of molecular diversity in disease is required for the development of
      targeted therapies. We have developed a screening method based on phage display
      to select peptides recognized by the repertoire of circulating tumor-associated
      antibodies. Here we isolated peptides recognized by antibodies purified from the
      serum of prostate cancer patients. We identified a consensus motif,
      NX(S/T)DK(S/T), that bound selectively to circulating antibodies from cancer
      patients over control antibodies from blood donors. We validated this motif by
      showing that positive serum reactivity to the peptide was specifically linked to
      disease progression and to shorter survival in a large patient population.
      Moreover, we identified the corresponding protein eliciting the immune response.
      Finally, we showed a strong and specific positive correlation between serum
      reactivity to the tumor antigen, development of metastatic androgen-independent
      disease, and shorter overall survival. Exploiting the differential humoral
      response to cancer through such an approach may identify molecular markers and
      targets for diagnostic and therapeutic intervention.

PMID- 12496766
TI  - The prostate, men and men's health.
AB  - Benign prostatic hyperplasia (BPH) is the most prevalent disease in the ageing
      male and the incidence of symptomatic disease is likely to increase in the
      millenium with increased life expectancy. BPH can have a severe impact on quality
      of life, including sexual function, and yet many men do not seek medical
      attention for this and many other diseases. Surgery is no longer a mandatory
      treatment for BPH. Medical management can provide excellent symptom relief and
      improvement in urinary flow rates, as well as quality of life, and men need to be
      made aware of this in order to make informed treatment decisions. In the broader
      context, men should be encouraged to become more health conscious and develop a
      more positive attitude towards their health.

PMID- 12496767
TI  - The pharmacological perspective: role for the sympathetic nervous system in
      micturition and sexual function.
AB  - The predominant effects of the sympathetic innervation of the lower urinary tract
      in man are mediation of contraction of the bladder base and the urethra and
      inhibition of the parasympathetic pathways at spinal and ganglion levels.
      Sympathetic tone also mediates the contractility of smooth muscle fibres in the
      prostatic stroma, and it has an important role in maintaining the penis in a
      flaccid state and in ejaculation. In the detrusor muscle of most species, beta
      adrenoceptors (beta-ARs) mediating relaxation normally dominate over alpha-ARs
      mediating contraction, and the effect of noradrenaline (NA) is relaxation. The
      human detrusor is able to express beta(1)-, beta(2)- and beta(3)-ARs and
      stimulation of beta(3)-ARs causes relaxation. Low, but reproducible expression of
      alpha(1)-ARs (alpha(1a) and alpha(1d)) has been found in human detrusor muscle,
      but the alpha(1)-AR subtypes mediating contraction have not been established. The
      sympathetic pathways to the penis may mediate anti-erectile as well as erectile
      effects. Although alpha(1) and alpha(2)-ARs have been demonstrated in human
      corpus cavernosum tissue, available information supports the view of a functional
      predominance of alpha(1)-ARs. The human vas deferens also has an important
      adrenergic innervation and alpha(1A)-ARs seem to mediate contraction.

PMID- 12496768
TI  - alpha(1)-Blocker therapy in the nineties: focus on the disease.
AB  - Therapy for benign prostatic hyperplasia has evolved rapidly over the last
      decade, with the introduction in the early 1990s of new agents such as alpha(1)
      blockers and 5alpha-reductase inhibitors. The major advantage of alpha(1)
      blockers over 5alpha-reductase inhibitors is their rapid onset of action. Maximum
      flow rate is improved after first administration and optimal symptom relief is
      usually reached within 2-3 months. In addition, alpha(1)-blockers are effective
      regardless of prostate size and they provide a similar degree of symptom relief
      in patients with or without bladder outlet obstruction. The main adverse events
      with the alpha(1)-blockers relate to their effects on the cardiovascular system
      (postural hypotension) and central penetration (asthenia, somnolence). Newer
      uroselective alpha(1)-blockers, such as alfuzosin and tamsulosin, have a better
      safety profile and, as such, do not require initial dose titration. Alfuzosin has
      also been shown in a six-month study to significantly reduce both residual urine
      and the incidence of acute urinary retention (AUR) compared with placebo. In
      addition, alfuzosin is effective in improving the success rate of a trial without
      catheter in patients with AUR.

PMID- 12496769
TI  - alpha(1)-Blockade in the nineties: focus on the patient.
AB  - Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia
      (BPH) are prevalent in 14-19% of men in their 40s, increasing to 43% in men >60
      y. Symptoms impact on patient's quality of life to varying degrees and more
      recently have been shown to affect sexual function. A number of question-naires
      are available which can assess symptom severity, quality of life and sexual
      function. Comparative studies in different countries show a similar trend, in
      that as symptom severity increases, then so does the interference with quality of
      life, general health status and sexual function. Treatment of LUTS is associated
      with an improvement in the quality of life of the patient. alpha(1)-Blockers are
      an established treatment of LUTS associated with BPH and, in addition, the
      alpha(1)-blocker alfuzosin has been shown to improve sexual drive and function.
      It is not yet known, however, whether this is a direct effect or due to a general
      improvement in the patient's quality of life. When treating BPH, physicians
      should be aware of the quality of life aspects to the disease, including sexual
      function, which is still an important feature in the ageing male.

PMID- 12496770
TI  - BPH in the next millennium:a glimpse to the future.
AB  - Benign prostatic hyperplasia (BPH) is a highly prevalent, age-related disease. As
      the world population continues to grow and life expectancy increases, the
      population of men suffering from BPH will expand. A greater emphasis will be
      placed on quality of life. The BPH patient of the future will also have greater
      expectations regarding therapy, which will need to be effective in a shorter
      period of time. New technologies for the treatment of BPH are anticipated.
      Already, robot-operated vaporisation of the prostate is being undertaken. With
      regard to medical therapy, more selective and hence, more effective drugs are
      under development. With the identification of new alpha(1)-adrenoceptor subtypes,
      alpha-blocker therapy should target the prostate more accurately. Gene-based
      therapies will have an important role in the future. It is envisaged that
      technology will exist whereby defective genes can be replaced and gene expression
      controlled to overcome the disease process. Through pharmacogenomics, drugs will
      be tail-ored to the individual, which will, in turn, result in more economical
      use of medical therapy. Similarly, the development of nanotechnology will allow
      site-specific delivery of drugs. Together, these advances will make the treatment
      of BPH even more effective in the new millennium.

PMID- 12496771
TI  - What's hot in the prostate?

PMID- 12496772
TI  - Editorial.

PMID- 12496773
TI  - Gynaecomastia: aetiology and treatment options.
AB  - This paper reviews the aetiology, prevalence and treatment of gynaecomastia.
      Gynaecomastia is a proliferation of male breast tissue apparently caused by
      alterations in the ratio of oestrogen:androgen levels. It is common in the
      general population, resulting from normal physiological changes and various
      pathological causes. Gynaecomastia is also induced by many drug treatments,
      including hormonal therapies for prostate cancer. Prophylactic radiotherapy
      appears to be effective against gynaecomastia in this population. Surgery is an
      option for intractable cases, and some medical treatments have been reported,
      although there is a paucity of data evaluating such therapies.

PMID- 12496774
TI  - Combined androgen blockade for advanced prostatic carcinoma.
AB  - Hormonal therapy has been mainstay of treatment for advanced forms of prostate
      cancer for over 50 y. The choice of hormonal therapy for carcinoma of the
      prostate depends not only on the desired progression-free and overall survival
      but also on the patient's quality of life, treatment costs and treatment
      toxicities. At the present time, several important questions have been raised
      over optimal treatment modalities for advanced prostate cancer. The optimal form
      of this therapy is still an enigma.

PMID- 12496775
TI  - Prostate-specific membrane antigen (FOLH1): recent advances in characterising
      this putative prostate cancer gene.

PMID- 12496776
TI  - Improving knowledge about prostate cancer: the development of an educational
      program for African-Americans.
AB  - This study aimed to develop and test a prostate cancer educational program, as
      well as an electronic keypad survey procedure, among African-Americans. A 1 h
      seminar and 12-item knowledge questionnaire were reviewed by both professional
      and lay consultants and then tested among African-American men and women
      recruited from the city of Chicago. Eight free presentations were delivered to a
      total of 63 attendees. Mean percent correct rose from 20% pre-program to 57% post
      program (P<0.001) and there was an increase on all individual questions. This
      feasibility study demonstrated: (a) there is a general lack of information about
      prostate cancer among African-Americans; (b) know-ledge can be significantly
      increased by means of an hour-long seminar; and (c) electronic keypads provide an
      easy, acceptable means of collecting data. Finally, the study underscored the
      need for the development of active and creative recruitment strategies to
      increase attendance. Such efforts are currently underway.

PMID- 12496777
TI  - Lymph node staging in clinically localized prostate cancer.
AB  - Pelvic lymph node involvement is an adverse prognostic factor in clinically
      localized prostate cancer, and a knowledge of nodal status is important for
      patient management. Whereas nodal disease has been widely regarded as incurable,
      evidence is now accumulating that some men with lymph node involvement may
      benefit from radical multimodality treatment approaches. Pelvic nodal status may
      be assessed by predictive nomograms, by imaging studies and by surgery. The pros
      and cons of each method are discussed together with the prospects for future
      development. Optimal strategies combining the different diagnostic approaches for
      the detection of lymph node metastases are considered in the context of the
      changing therapeutic implications of nodal disease.

PMID- 12496778
TI  - Cell turnover in human seminal vesicles and the prostate: an immunohistochemical
      study.
AB  - The human prostate and seminal vesicles are both androgen-dependent sex accessory
      organs. Their growth behavior, response to hormone manipulation, susceptibility
      to benign and malignant processes and sex accessory functions, however, differ
      greatly. The growth behavior of most tissues correlates well with the cell
      turnover rate of that tissue. Therefore, we compared the cell turnover of normal
      human prostate and seminal vesicles. Immunohistochemical expression of MIB-1
      (proliferation), bcl-2 and transforming growth factor (TGF beta) were examined in
      20 different samples taken from histologically normal human prostatic and seminal
      vesicle tissue. For the quantification of apoptosis, the TUNEL technique was
      used. The apoptosis rates in normal prostatic tissue (0.73+/-0.60) were
      significantly greater (P=0.003) than those seen in seminal vesicles (0.02+/
      0.01). The proliferation rates also differed significantly (P=0.002) between
      these tissues (prostate: 0.77+/-0.78; seminal vesicles: 0.02+/-0.02). Eighty
      percent of the prostate tissue stained for bcl-2, whereas only 55% of the seminal
      vesicle tissue showed staining for bcl-2. All seminal vesicles and 75% of the
      prostate samples stained for TGF beta. For both androgen-dependent tissues,
      apoptotic rates closely equaled proliferation rates. The cell turnover, however,
      was much higher in the prostate than in the seminal vesicles. TGF beta seems to
      be more important for the regulation of cell turnover in the seminal vesicles
      than bcl-2. These differences in the proliferative behavior may explain why
      disturbances of apoptotic regulation lead to a more extensive net cell gain in
      prostatic tissue compared to the seminal vesicles. This might help explain the
      vastly different incidence of benign and malignant tumors in these organs.

PMID- 12496779
TI  - Allelic losses at 8p, 10q, 11p, 13q, 16q, 17p, and 18q in prostatic carcinomas:
      The impact of zonal location, Gleason grade, and tumour multifocality.
AB  - Molecular genetic investigations have made it clear that the development and
      progression of prostate cancer is associated with losses of genetic material in
      certain chromosomal arms. However, there are only few data about the question of
      whether the zonal location, a higher Gleason grade, or multifocality of the
      tumour have any influence on the pattern of allelic losses. In the present study,
      48 tumour foci from 32 radical prostatectomy specimens were investigated for
      allelic losses at chromosomes 8p, 10q, 11p, 13q, 16q, 17p, and 18q with a set of
      20 microsatellite markers. The results were analysed for the zonal location of
      the tumour foci and the presence of a Gleason grade 4 differentiation. Overall,
      focal allelic losses at 8p, 10q, 11p, 13q, 16q, 17p, and 18q were observed in
      62.5%, 17.2%,. 3.2%, 18.8%, 40%, 9.7%, and 22.6% of the 32 cases, respectively.
      Comparing the frequencies of allelic losses with the zonal location or the
      Gleason grade, no highly significant correlations were found at any chromosomal
      locus investigated. However, the observation of different patterns of allelic
      losses in 12 of 14 cases containing more than one tumour focus indicates a high
      rate of genetic heterogeneity. We conclude that allelic losses at the chromosomal
      loci investigated are not strongly associated with a specific zonal location or a
      higher Gleason grade of prostatic carcinoma. Genetic heterogeneity of multiple
      tumour foci within one gland might contribute to the difficulties in predicting
      the prognosis for this common malignancy.

PMID- 12496780
TI  - Effects of hCG stimulation after withdrawal of long-term oestrogen treatment in
      patients with prostate carcinoma.
AB  - Testosterone depletion is the keystone for therapy of patients metastic prostatic
      carcinoma. Our objective was to investigate Leydig cell function and testosterone
      levels after withdrawal of long-term endocrine treatment in patients with
      prostatic carcinoma. Thirteen patients with prostatic carcinoma, previously
      treated with oestrogens for at least 4 y, were stimulated with 5000 IU human
      chorionic gonadotrophin (hCG). The stimulation was performed 3-6 y after
      cessation of the oestrogen therapy. Serum concentrations of testosterone,
      luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured
      before and 24 and 48 h after hCG stimulation. Before hCG stimulation all patients
      had low serum testosterone concentrations (mean 2.0+/-0.2 nmol/l) and 24 and 48 h
      after hCG stimulation the values had not significantly increased (mean 2.4+/-0.2
      and 2.5+/-1.1 nmol/l, respectively). LH and FSH were within or above the normal
      range before but after hCG stimulation the values significantly increased. In
      conclusion, the study shows that the Leydig cells were unable to respond to hCG
      stimulation more than 3 y after cessation of oestrogen therapy. The Leydig cell
      function seems to be irreversibly impaired by long-term oestrogen treatment.

PMID- 12496781
TI  - Innovators in Urology.

PMID- 12496782
TI  - The change in free-to-total prostate-specific antigen during progression to
      androgen-independent state in prostate cancer patients: utilization for
      intermittent androgen suppression therapy.

PMID- 12496783
TI  - Artificial neural network analysis and the relationship of P53 and P21(waf-1)
      protein expression with prognosis of advanced stage prostate cancer treated by
      androgen ablation.

PMID- 12496784
TI  - Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan.

PMID- 12496785
TI  - Transductional targeting of adenoviral vectors to prostate cancer in vitro.

PMID- 12496786
TI  - Biopsying prostate gland: telomerase evaluation.

PMID- 12496788
TI  - Potent induction of carcinogen defence enzymes with sulforaphane, a putative
      prostate cancer chemopreventive agent.

PMID- 12496787
TI  - Clinical and pathologic significance of T1c adenocarcinoma of the prostate
      cancer.

PMID- 12496789
TI  - Phase III study on intermittent MAB vs continuous MAB: an international co
      operative study.

PMID- 12496790
TI  - Prostatic cancer: comparison of the traditional prognostic parameters, DNA
      analysis results based on flow cytometry and immuno-histochemical expression of
      protein p53.

PMID- 12496791
TI  - Differential RNA expression of the pS2 gene in the human benign and malignant
      prostatic tissue.

PMID- 12496792
TI  - Efficacy and limitations of delayed/salvage radiation therapy after radical
      prostatectomy.

PMID- 12496793
TI  - Autologous blood transfusion as a potential source of prostate cancer cells
      spread during radical prostatectomy.

PMID- 12496794
TI  - Dual regulation of urokinase gene expression in human prostate cancer.

PMID- 12496796
TI  - PSA nadir and risk of non-organ-confined disease in radical prostatectomy
      preceded by neoadjuvant androgen deprivation.

PMID- 12496795
TI  - Targeting anti-apoptotic genes with antisense oligodeoxy-nucleotides to delay
      progression to androgen independence.

PMID- 12496797
TI  - Predictive value of decreased p27 Kip1 protein expression for the recurrence-free
      and long-term survival of prostate cancer patients.

PMID- 12496798
TI  - Activation of TGF-beta signalling in human prostate cancer cells suppresses
      tumorigenicity via deregulation of cell cycle progression and induction of
      caspase-1 mediated apoptosis: significance in prostate tumorigenesis.

PMID- 12496799
TI  - Quality of life outcomes after brachytherapy for early prostate cancer.

PMID- 12496800
TI  - Hyaluronic acid and hyaluronidase: molecular markers associated with prostate
      cancer biology and detection.

PMID- 12496801
TI  - Update of clinical and basic science research on prostate cancer from the
      department of defense center for prostate disease research (DOD-CPDR).

PMID- 12496802
TI  - Determination of the enzyme telomerase in needle biopsies and fine needle
      aspiration cytology samples of the prostate in the diagnosis of prostate cancer.

PMID- 12496803
TI  - Association of vitamin D receptor gene polymorphism with protection against
      prostate cancer and benign prostate hyperplasia.

PMID- 12496804
TI  - Effect of prior therapy on survival after salvage cryotherapy for recurrent
      prostate cancer.

PMID- 12496805
TI  - Suicide gene therapy in the rat model of prostate cancer.

PMID- 12496806
TI  - Intraprostatic AD-p53 gene therapy followed by radical prostatectomy: feasibility
      and preliminary results.

PMID- 12496807
TI  - Diagnostic improvement of prostate cancer using an extensive biopsy protocol.

PMID- 12496808
TI  - The effect of castration on tumour growth rate and cell kinetics in hormone
      sensitive and hormone-insensitive rat prostatic adenomas.

PMID- 12496809
TI  - Molecular characterisation and racial distribution of androgen and vitamin D
      receptor polymorphisms in patients with prostate cancer, benign prostatic
      hyperplasia and age-matched healthy controls.

PMID- 12496810
TI  - Effective induction of apoptosis in human prostate carcinoma cells by vitamin E
      succinate.

PMID- 12496811
TI  - Quality of life comparison of radical prostatectomy and interstitial
      brachytherapy in the treatment of clinically localized prostate cancer.

PMID- 12496812
TI  - Augmented cytotoxicity of estramustine and etoposide combination in hormone
      refractory prostate cancer cell lines and association with TGF modulation.

PMID- 12496813
TI  - Caspase protease manipulation: a novel approach to apoptotic induction in
      prostate cancer.

PMID- 12496814
TI  - G-rich sequence factor 1, a novel marker of prostate cancer virulence identified
      through mRNA differential display.

PMID- 12496816
TI  - Delegate list.

PMID- 12496815
TI  - Is one set of transrectal sextant biopsies enough to rule out prostate cancer? A
      prospective evaluation.

PMID- 12496819
TI  - Editorial.

PMID- 12496818
TI  - What's hot in the prostate?

PMID- 12496820
TI  - Alpha-1-adrenoceptor blockade in the treatment of benign prostatic hyperplasia.
AB  - In light of the growing interest in the concept of 'uroselectivity' and in the
      increased worldwide use of alpha-blockers for benign prostatic hyperplasia (BPH),
      this review evaluates the relative benefits of various alpha-blocking agents in
      the treatment of BPH. The pharmacological and physiological selectivity as well
      as the clinical efficacy and safety of alfuzosin, doxazosin (Cardura(R)),
      tamsulosin (Flomax(R)), and terazosin (Hytrin(R)) are compared. In reviewing
      efficacy and safety, emphasis is given to 17 placebo-controlled, double-blind
      trials of these alpha-blockers published in peer-reviewed journals. This review
      also considers long-term data, effects on blood pressure, costs, and dose ranges.

PMID- 12496821
TI  - Clinical trials in prostatic cancer-interpretations and misinterpretations.
AB  - New agents and therapies in prostate cancer, as in other diseases, need to be
      accurately, comprehensively and logically developed. The golden standard, a
      prospective, randomised phase III study can only be carried out efficiently if
      phase I and phase II studies have been completed. The advent of new therapies
      which will be used in early stage disease, necessitates the development of new
      methods of measuring their activity and correlating it with an influence on the
      natural history of the disease. Efforts to get results more quickly by using
      weaker endpoints and retrospectively carrying out metanalyses have their
      disadvantages and dangers. This review will attempt to investigate how clinical
      trials from phase I through to phase IV in prostate cancer might be improved and
      made more easily interpretable. It will cover such aspects as the recruitment to
      trials, the demands of good clinical practice, the use of surrogate endpoints and
      attempt to give some indications how the newer therapeutic options can be
      reliably and quickly investigated through clinical trials.

PMID- 12496822
TI  - Molecular and cellular biology of prostate cancer-the role of apoptosis as a
      target for therapy.
AB  - Despite the high incidence and mortality rate of prostate cancer, the molecular
      mechanisms underlying the progression of the disease remain to be fully
      elucidated. This paper reviews the current state of knowledge on prostatic
      carcinogenesis, focusing not only on the molecular genetics of prostate cancer,
      but also on the role of oncogenes, tumour suppressor genes, and growth factors.
      The remarkable ability of prostate cancer cells to survive androgen withdrawal
      and apoptosis are discussed, with particular emphasis on how apoptosis may be
      manipulated from a therapeutic viewpoint.

PMID- 12496824
TI  - Interstitial laser coagulation in the treatment of benign prostatic hyperplasia
      using a diode laser system: results of an evolving technology.
AB  - Interstitial laser coagulation (ILC) treatment is a recent technique in the
      treatment of BPH that is evolving rapidly. The results of a prospective
      randomised study vs transurethral resection of the prostate (TURP) is presented
      as well as results of patients treated with a temperature sensing laser system.
      The first study included 44 patients treated in a prospective randomised study
      (randomisation ILC vs TURP=2:1) comparing changes in objective and subjective
      parameters. In the second part of the study the outcome of the treatment of 34
      patients with BPH using ILC performed with a temperature-sensing laser system are
      presented. The clinical outcome at 12, 26, 52 and 104 weeks was evaluated with
      symptom scores, quality of life measures, changes in voided volume, post void
      residual, and peak flow rate. In addition changes in prostate volume and
      urodynamic parameters at half a year follow-up are presented. In this randomised
      study patients improved markedly at any time during follow-up. In the ILC group
      there was a significant and persisting subjective improvement whereas the
      improvements in the TURP group were even more significant. The changes in voiding
      parameters, including changes in pressure-flow parameters, are superior in the
      TURP group compared to the changes in the ILC group. The retreatment rate for the
      ILC group is 21% compared to 7% in the TURP group, no patient with incontinence
      was documented in either group, while only one patients in the TURP group
      developed a urethral stricture. In the second part of the study, the clinical
      improvements following laser therapy using the temperature sensing treatment mode
      were more pronounced in voiding parameters when compared to those of the
      randomised laser group. Lower energy interstitial laser treatment of the prostate
      results in a significant improvement of all clinical parameters that are inferior
      to improvement following transurethral resection of the prostate. When using a
      temperature sensing system, the objective results of laser treatment improved and
      seem to be more durable.

PMID- 12496823
TI  - Time-resolved fluorescence imaging (TRFI) for direct immunofluorescence of PSA
      and alpha-1-antichymotrypsin in prostatic tissue sections.
AB  - We have developed a direct immunofluorescence technique utilising chelates of the
      lanthanide ions europium and terbium conjugated to monoclonal IgGs (Mabs) against
      prostate-specific antigen (PSA) and alpha-1-antichymotrypsin (ACT) for the
      detection and quantification on the same tissue section. Strong signals without
      disturbance from tissue autofluorescence were demonstrated in paraffin sections
      of ten benign and six malignant prostate tissue specimens. The signal intensity
      increased linearly with the amount of labelled Mab until epitope saturation
      began. The highest concentrations of bound IgG in tissue sections were 27.3
      fmol/pixel for ACT and 7.2 for PSA. Time-resolved fluorescence imaging (TRFI)
      offers an attractive method for histochemical studies based on specific and
      quantitative detection of fluorescent lanthanide chelates.

PMID- 12496825
TI  - Prostate specific antigen levels in the follow up of localised prostate cancer:
      how does radiotherapy compare to radical prostatectomy?
AB  - This study aimed to evaluate tumor progression as assessed by PSA level of
      curative treatment for localised prostate cancer by either radiotherapy or
      prostatectomy. From 1987 to 1993, 180 patients were treated for clinically
      localised prostate cancer either by radiotherapy or prostatectomy. One hundred
      and five patients with clinical T1T2N0M0 were eligible for this study. Forty five
      underwent external beam radiotherapy and 60 had a radical prostatectomy. After
      radiotherapy PSA slowly decreased to reach a nadir 18 months after treatment. Any
      subsequent increase from this lowest post treatment level is associated with
      tumor progression. After radical prostatectomy PSA becomes undetectable and any
      increase will be regarded as evidence of tumor progression. The median PSA level
      before treatment and the median length of follow-up were comparable for the two
      groups. There was no statistically significant difference in overall survival and
      biological evidence of disease progression at 5 y. Analysis of the evolution of
      median PSA level shows a progressive decline during the 4 y after radiotherapy.
      After radical prostatectomy PSA become undetectable, 4 y after treatment PSA
      levels become comparable in the two groups. The biochemical free survival was 60%
      for the prostatectomy group and 62% for the radiotherapy group. PSA is an
      effective marker of tumour progression after surgery or radiotherapy for
      localised prostate cancer. In our retrospective study recurrence rates at 5 y
      were not significant but direct comparisons are limited due to the Gleason score
      of the two groups. PSA levels can take up to 4 y to reach a nadir after
      radiotherapy.

PMID- 12496826
TI  - Use of prostatic massage in combination with antibiotics in the treatment of
      chronic prostatitis.
AB  - Chronic prostatitis is often refractory to antibiotics, however biopsy and
      molecular data indicate persistent symptoms may be due to occult infection.
      Combining antibiotic therapy with regular prostatic massage has been suggested as
      an effective therapy for some of these men. From November 1996 to December 1998,
      73 men with chronic pelvic pain syndromes were treated with antibiotics and
      prostatic massage. Antibiotic selection was based on culture and sensitivity of
      prostatic fluid or empirically if cultures were negative. Prostatic massage was
      done 1 to 3 times per week and fluid examined for WBCs and cultured for bacteria.
      The average age of the group was 43.5 y (range 23-72) and average duration of
      symptoms 6.7 y (median 3 y, range 3 months-30 y). Prostatic cultures were
      negative in 19, grew uropathogens in 2, and Gram positive bacteria in 52
      patients. Overall 29 patients (40%) had complete resolution of symptoms, 14 (19%)
      had complete resolution followed by a recurrence, 15 (21%) had some improvement
      and 15 (21%) had no improvement. All positive cultures were sterilized during
      treatment. Combination prostatic massage and culture specific antibiotics can be
      an effective treatment in a proportion of men with long standing refractory
      chronic prostatitis.

PMID- 12496827
TI  - Introduction.

PMID- 12496828
TI  - Intermittent versus continuous hormone deprivation in metastatic prostate cancer:
      preliminary data from an ongoing European study.

PMID- 12496830
TI  - Is there a place for neoadjuvant hormonal therapy before radical prostatectomy or
      radiation therapy in the management of prostate cancer?

PMID- 12496829
TI  - Immediate or deferred hormone ablation in PSA relapse after radical
      prostatectomy.

PMID- 12496831
TI  - Will modern molecular methods such as reverse transcriptase-polymerase chain
      reaction improve the prediction of prognosis in prostate cancer patients?

PMID- 12496832
TI  - Results of a screening program in Germany for early detection of early prostate
      cancer.

PMID- 12496833
TI  - Summary.

PMID- 12496835
TI  - What's hot in the prostate?Think tank workshop on localised prostate cancer.

PMID- 12496836
TI  - Editorial.

PMID- 12496837
TI  - Strategies for the chemoprevention of prostate cancer, Brussels, Belgium, October
      30-31, 1998.

PMID- 12496839
TI  - Medical management of BPH: Where are we going? 

PMID- 12496838
TI  - Are we making an impact on prostate cancer?

PMID- 12496840
TI  - Insulin-like Growth Factor (IGF) Network and Prostate Pathologies.
AB  - The Insulin-like Growth Factor (IGF) network in prostate tissue represents a key
      element in normal and tumour growth. It can provide us with new markers for
      prognosis or diagnosis and targets for treatment of prostate diseases. This short
      review introduces the IGF network in general and in the prostate gland,
      summarises the modifications observed in tumours and discusses the importance of
      a new family of low affinity IGF-binding proteins. Further studies on the IGF
      network will enrich our understanding of prostate tumourigenesis and its control
      and therefore provide new therapeutics to master the IGF network

PMID- 12496841
TI  - Pathologic progression of autochthonous prostate cancer in the TRAMP model.
AB  - The ability to manipulate gene expression in specific cell types at specific
      times utilizing transgenic technology has allowed the development of novel mouse
      model systems that can mimic human disease. We have previously established the
      Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model for prostate cancer
      using the rat probasin promoter to direct expression of the SV40 early genes to
      prostate epithelium. Male TRAMP mice exhibit consistent prostate-specific
      patterns of expression and develop prostatic intraepithelial neoplasia that will
      become invasive and metastasize primarily to the lymph nodes and lungs. In this
      paper we report our continued experience with this model and present a
      standardized histologic grading system to designate low and high grade prostatic
      intraepithelial neoplasia and well, moderate, and poorly differentiated prostate
      adenocarcinoma. In addition, we demonstrate the persistence of androgen receptor
      expression during pathologic progression and characterize heterogeneous
      cytokeratin expression in localized and metastatic prostate cancer. Finally, we
      report on our observations that phenotypic variability in tumor and pathologic
      progression in TRAMP occurs as a function of genetic background.

PMID- 12496842
TI  - Characterization of the FGF axis and identification of a novel FGFR1iiic isoform
      during prostate cancer progression in the TRAMP model.
AB  - Expression of the fibroblast growth factor (FGF) axis was examined during
      prostate cancer progression in the autochthonous Transgenic Adenocarcinoma of
      Mouse Prostate (TRAMP) model, including TRAMP derived cell lines. Transcripts for
      FGF-7 and FGF-10 that are normally expressed by the stroma were detected in all
      samples, including the epithelial cell lines, suggesting that elaboration of
      these factors by the epithelium may be an essential event during transformation.
      Interestingly FGFR2iiib, the FGF-7 and FGF-10 receptor, was downregulated during
      tumor progression whereas a novel FGFR1iiic (Phi) inframe splice form was found
      to be expressed. These observations support the hypothesis that specific changes
      in FGF axis correlate with, and probably facilitate, tumor progression.

PMID- 12496843
TI  - Estramustine in combination with vinblastine and mitomycin-C for patients with
      progressive androgen independent adenocarcinoma of the prostate.
AB  - A phase II trial was performed to assess the antitumor activity and toxicity of
      estramustine in combination with vinblastine and mitomycin-C in 46 consecutive
      patients with androgen independent prostate cancer. All patients presented with
      disease progression following castrate serum testosterone levels and were treated
      for six consecutive weeks with three daily 140 mg doses of oral estramustine,
      vinblastine at 5 mg/m(2) weekly by intravenous bolus and mitomycin-C at 15
      mg/m(2) every six weeks by intravenous bolus. Prostate specific antigen levels
      decreased by greater than 50% from baseline in 16 (41%; 95% CI 25-58%) and
      normalized in 11 (28%; 95% CI 14-45%) of 39 evaluable patients. Patients who
      demonstrated a greater than 50% reduction in PSA had a longer delay in time to
      disease progression. Non-hematologic toxicity was mild, predominately
      gastrointestinal. Hematologic toxicity was apparent in five patients with Grade
      III granulocytopenia and in 21 patients with Grade IV granulocytopenia of 43
      evaluable patients for toxicity. Three patients were admitted to the hospital for
      neutropenic fever. Eight patients had Grade III thrombocytopenia, four patients
      had Grade IV thrombocytopenia, no bleeding occurred. Estramustine in combination
      with vinblastine and mitomycin-C is an active regimen. The non-hematologic
      toxicity was tolerable, while the hematologic toxicity required individual dosage
      reduction. The combination and the clinical significance of the decline in the
      PSA warrants further investigation.

PMID- 12496844
TI  - Antibiotic prophylaxis for prostate biopsy: benefits and costs.
AB  - Transrectal ultrasound-guided core biopsy is a widely used method to diagnose
      prostate cancer. It is generally considered a safe procedure but the main concern
      is that significant complications such as infections do occur. To evaluate the
      effect of a combined two-dosage antibiotic prophylaxis with ciprofloxacin and
      metronidazole, a prospective study of 289 patients undergoing core-biopsy of the
      prostate was performed. Five patients (1.7%) developed urinary tract infection
      and all did recover without any further complications. The infection rate was
      significantly lower compared to our historic controls receiving no prophylaxis at
      all. This prophylactic regime resulted in a low infection rate and it was
      feasible from the patient perspective. The total cost of antibiotic medication
      and additional costs due to complications was 18 USD per patient and the cost
      effectiveness compared to no prophylactic therapy at all was considered good.

PMID- 12496845
TI  - Characterization and processing of prostate specific antigen (hK3) and human
      glandular kallikrein (hK2) secreted by LNCaP cells.
AB  - Prostate specific antigen (PSA, hK3) in serum is predominantly complexed to alpha
      1-antichymotrypsin (ACT), but a minor fraction remains in a free form despite the
      very large excess of serine protease inhibitors and alpha-2-macroglobulin. The
      fraction of free to total PSA is significantly lower in prostate cancer (CaP)
      compared to benign prostatic hyperplasia (BPH) which provides improved
      discrimination of these conditions. The molecular nature of free PSA in the
      circulation and the reason for its varying concentration in malignant and benign
      conditions is currently not known. The objective of the present investigation was
      to study the secretion of PSA and human glandular kallikrein 2 (hK2) by the LNCaP
      prostate cancer cell line, and to purify and characterize both proteins. LNCaP
      PSA was thoroughly characterized by immunological characterization, SDS-PAGE,
      isoelectric focusing, gel filtration, aminoterminal sequencing, reverse-phase
      chromatography, mass spectrometry and enzymatic activity measurements. LNCAP
      cells produced approximately equal amounts of zymogen (proPSA) and the one-chain
      mature form of PSA, whereas there was no evidence for the secretion of any
      internally cleaved forms. LNCaP cells secreted hK2 into the growth medium at
      about 3-5% of the amount of PSA. One-chain, mature PSA and hK2 obtained when
      LNCaP cells were grown in the presence of fetal bovine serum, had no enzymatic
      activity, but were active when the cells were grown in the absence of serum.
      Using enzymatically active recombinant hK2, it was possible to activate proPSA
      secreted by LNCaP cells. ProPSA formed two bands with high isoelectric points
      (8.2 and 8.4), which disappeared when proPSA was converted to mature PSA with
      hK2. Cancerous cells produce the zymogen forms of PSA, which by their isoelectric
      pI points seem to be found in serum of prostate cancer patients, but not BPH
      patients. Mature, one-chain PSA is inactive in the presence of serum. These
      findings may be highly relevant for the understanding of the generation of free
      and complexed PSA in the circulation.

PMID- 12496846
TI  - High energy transurethral thermotherapy in the treatment of benign prostatic
      hyperplasia: criteria to predict treatment outcome.
AB  - In this study we analyzed the individual value of baseline parameters to predict
      the outcome of high energy transurethral microwave thermotherapy in the treatment
      of patients with lower urinary tract symptoms and benign prostatic hyperplasia.
      Two hundred and forty-seven patients with symptomatic benign prostatic
      hyperplasia were treated with high energy microwave thermotherapy using the
      software 2.5 (Prostatron). Mean age at the time of treatment was 66.3 (s.d. 8.2)
      y, the mean prostate volume 57.0 (s.d. 25.2) cc and the mean energy applied was
      159 (s.d. 40) KJ. Multi variable analysis on baseline parameters was performed to
      evaluate their predictive value for response using the WHO-response evaluation
      criteria for IPSS, maximum flow and urodynamic obstruction (linPURR). At 1 y
      follow-up a 57% increase in maximum flow and a 59% decrease in symptom score was
      noticed following high energy transurethral thermotherapy. The percentage of good
      responders varies between 12% and 34% depending on the stratification (IPSS,
      Q(max) and linPURR), the percentage of intermediate responders in these
      categories varies between 17% and 60% and the percentage of poor responders
      varies between 20% and 49%. Independently predictive baseline parameters for poor
      response were patients' age, prostate size and grade of bladder outlet
      obstruction (BOO). The total amount of energy delivered during treatment is also
      correlated with response. For the case selection for high energy transurethral
      microwave thermotherapy three baseline parameters can be identified which predict
      response for at least one response evaluation criterium: age, prostate size,
      grade of bladder outlet obstruction (BOO) and total amount of TUMT-energy.
      Especially the total amount of TUMT-energy is strongly predictive for all three
      response evaluation criteria, which suggests an important contribution of other
      mechanisms such as vascularisation and tissue composition to the outcome of high
      energy TUMT treatment.

PMID- 12496848
TI  - Introduction.

PMID- 12496847
TI  - Immunohistochemical BCL-2 and Ki-67 expression predict survival in prostate
      cancer patients followed expectantly.

PMID- 12496849
TI  - Prostate cancer: epidemiology and screening.

PMID- 12496850
TI  - Pathology and bio markers of prostate cancer.
AB  - This session included five presentations in the areas of pathology of precursor
      lesions and carcinoma of the prostate, the value of determining neovascularity in
      the diagnosis and staging of prostate cancer, new 'molecular' markers,
      correlation between pre- and postoperative Gleason scores and a study dealing
      with transition zone PSA density. The abstracts and talks are summarized in the
      next few pages.

PMID- 12496851
TI  - Early Diagnosis and Staging.
AB  - This report reviews developments in the early diagnosis and staging of prostate
      cancer and updated on the incidence of postate cancer to discuss the pros and
      cons of population based screening. Refinements and reliability of various
      diagnosic procedures are described such as PSA testing, transrectal ultrasound,
      ratio beteen PSA-level and ultrasound measured prostate volume, rate of change of
      PSA-level, combination factor equations computed by neural network programs to
      predict likelihood of prostate cancer, artificial neural network analysis of
      subvisual transrectal ultrasound information, measurements of different PSA-forms
      of PSA (in particular percent free PSA), and glandular kallikrein 2.

PMID- 12496852
TI  - Refractory disease, new horizons and patient-physician relationships.
AB  - Understanding the role of chemotherapy for prostate cancer has advanced along two
      axes, better definition of endpoints, and biologic understanding of disease
      targets. Use of PSA as a surrogate endpoint makes possible the more rational
      design of phase III trials which will include survival and disease free intervals
      as an endpoint. Pain control has emerged as an important treatment endpoint
      through which more cost-effective care can be envisioned. Discovery of growth
      factor interactions with prostate cancer cells and the elucidation of apoptotic
      pathways have provided numerous new targets for biologic and chemotherapy of
      advanced disease.

PMID- 12496853
TI  - Advanced prostate cancer.
AB  - Both the definition and therapy of advanced prostate cancer is challenging. The
      advanced prostate cancer session at "The 8th International Prostate Cancer
      Update" had discussions which tried to answer the questions of management of
      these patients who either present with advanced disease or fail any form of
      therapy for clinically confined prostate cancer. This article provides an
      overview of therapeutic options: monotherapy and minimal androgen blockade
      options versus maximal androgen blockade, adjuvant therapy, intermittent therapy
      and timing of therapy as well as chemotherapy when all these measures fail. The
      impact of these therapies on progression as well as quality of life is reviewed.

PMID- 12496854
TI  - Strategies for chemoprevention of prostate cancer.
AB  - Because prostate cancer has a long latency and high incidence, it is a good
      target for chemoprevention by agents such as retinoids, antiandrogens,
      antiestrogens, and vitamin D analogs. Phase II chemoprevention trials are
      frequently conducted on cohorts of patients with previous cancers or premalignant
      lesions who are scheduled for prostate cancer surgery; such trials are currently
      in progress with several agents. Prostatic intraepithelial neoplasia (PIN) can be
      used as a surrogate endpoint biomarker for prostate cancer incidence. Studies of
      men with high-grade PIN (HGPIN) are particularly useful in that they require a
      much smaller cohort of 200-400 patients instead of the 18 000 patients required
      for typical Phase III trials. Even with a smaller sample size, statistically
      significant evidence of cancer prevention is achieved due to the high probability
      of HGPIN progressing to cancer (35-55%). A Bayesian sequential monitoring system
      allows interim analysis of biomarker modulation as early as the completion of 30
      patients. Putting all these strategies together will help inhibit, delay, or
      modulate the natural history of prostate carcinogenesis.

PMID- 12496856
TI  - Paper.

PMID- 12496855
TI  - Medical therapy for BPH: expanding our treatment paradigm?
AB  - Medical therapy for relief of symptoms of benign prostatic hyperplasia (BPH) is
      now a clinical reality. The challenge for urologists treating BPH with medical
      therapy is how to rationally employ the two proven classes of medications,the
      alpha blockers and finasteride, in their practice. To accomplish this, we must
      critically examine the results of multiple important clinical BPH trials
      published over the last decade and examine the short and long term effect of the
      various available medical therapies on symptoms, objective progression and
      consequences of the disease process and whether evidence based indicators will
      allow us to choose appropriate therapies. It appears that we can rationalize our
      medical therapy decisions, taking into consideration severity of disease,
      prostate size (and perhaps PSA) and most importantly, the patients' longterm
      expectations for treatment outcome. But first physicians must decide for
      themselves whether to expand their treatment paradigm beyond short term symptom
      relief to encompass long term durability and even prevention of the consequences
      of the long term progression of BPH.

PMID- 12496858
TI  - Editorial.

PMID- 12496857
TI  - What's hot in the prostate?

PMID- 12496859
TI  - Maximum androgen-blockade with medical or surgical castration in advanced
      prostate cancer: A meta-analysis of nine published randomized controlled trials
      and 4128 patients using flutamide.
AB  - With the recent Southwest Oncology Group (SWOG) publication of their metastatic
      prostate cancer clinical trial results, which concluded that orchiectomy and
      flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does
      not significantly improve survival (NCI 0105), and the 1989 publication from the
      same cooperative group indicating a 24% improvement in survival for MAB therapy
      with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may
      well be undecided about the likelihood of clinical benefits with flutamide in
      combination with medical or surgical castration. To better characterize this
      important therapeutic decision, we assessed the survival benefit of MAB therapy
      with flutamide through a meta-analysis of up-to-date information from studies
      reported/conducted from 1989 through 1998. All peer-reviewed published randomized
      controlled trials comparing treatment with flutamide plus either lutenizing
      hormone releasing hormone (LhRH) agonists or orchiectomy as MAB treatment with
      LhRH or orchiectomy alone were included. The primary objective of the study was
      to form a combined estimate and confidence interval for the hazard ratio (as
      measured by the relative risk (RR) of survival in a comparison of castration vs
      MAB) summarizing the effect of flutamide treatment on overall survival. Directly
      extracted estimates of the log hazard ratio were used if available (1 study); if
      not, either an estimate of the RR based on a reported P-value from a log rank
      test (7 studies) or a discrete proportional hazards approximation based on
      reconstructed annual life tables for the treatment arms (1 study) were used. Nine
      studies with 4128 patients with advanced prostate cancer were included in these
      analyses. Pooled estimates demonstrated a 10% improvement in overall survival
      with flutamide as MAB therapy (relative risk (RR)=0.90, 95% Confidence
      Interval=0.79, 1.00). The currently available updated evidence from randomized
      trials shows a 10% benefit in overall survival with flutamide as MAB therapy in
      comparison to conventional castration, almost identical to the estimate reported
      in the recently published Southwest Oncology Group Study (NCI 0105).

PMID- 12496860
TI  - Genetic predisposition to prostate cancer.
AB  - Prostate cancer has been known to run in families for about 40 years and
      epidemiological studies have demonstrated an increased risk to close relatives of
      cases. This risk rises markedly when the closeness and number of cases in a
      cluster increases. There has been considerable debate about the genetic model, in
      particular whether there is a commoner lower penetrance (moderately increased
      risk of the disease due to the gene(s)) in addition to contribution from high
      risk genes. For the first time, molecular results are starting to emerge,
      indicating the location of high risk genes. These have shown that there is
      evidence for more than one site of a high risk, gene two sites on chromosome 1
      and one on chromosome X. These do not account for all clusters of prostate cancer
      cases and further genes remain to be discovered. This article also outlines the
      contribution of the numerous collaborators in the British Prostate Group to the
      UK Familial Prostate Cancer Study.

PMID- 12496861
TI  - Immunohistochemical evaluation of the safety of transurethral electrovaporization
      of the prostate and its clinical results.
AB  - Short term follow up studies on transurethral electrovaporization (TUEVP) have
      shown a relative low morbidity over TURP. The use of high power current has been
      claimed as a source of possible damage on the neuronal structures surrounding the
      prostate. The aims of our study were to assess longer follow up results as well
      as the safety of this technique. Over an 18 month mean follow up period symptom
      relief remained relatively stable. Postoperative dysuria was detected in a higher
      percentage of patients and was seen for a longer period in comparison with
      previous reports. Immunohistochemical staining performed using S-100 and NF
      monoclonal antibodies showed anatomical integrity of the prostatic neuronal
      fibres surrounding the vaporization edge. In conclusion, although the
      effectiveness and safety of TUEVP are confirmed by the present study, the
      occurrence of a significant rate of long-lasting postoperative irritative
      symptoms must be taken into account.

PMID- 12496862
TI  - Eight year improvement in pathological results after radical prostatectomy.
AB  - The purpose of this paper is to compare the pathological stage of prostate cancer
      specimens with preoperative characteristics according to the year of diagnosis.
      One hundred and seventy five patients underwent radical prostatectomy for
      localized disease between January 1989 and December 1996. In each year group, the
      mean preoperative PSA (Prostate Substance Antigen, Hybutech((R)) Assay
      Nl<urgr/ml), digital rectal findings, Gleason grade, pathological staging, and
      postoperative and follow-up PSA values were prospectively recorded and compared.
      The mean PSA value was the only preoperative parameter that significantly fell
      with time (from 52-12.2 ngr/ml between 1989 and 1996), and correlated with a
      higher percentage of organ-confined disease (40% vs 81.8%). Biological
      progression one year after radical surgery decreased from 60% in 1989 to 4.5% in
      1996. Results of radical prostatectomy are improving with time, corresponding to
      lower preoperative PSA values. This might result from earlier diagnosis of
      prostate cancer based on PSA, though the number of insignificant cancers is not
      increasing.

PMID- 12496863
TI  - Adenovirus-mediated gene transfer in dog prostate: a preclinical study of a
      relevant model system for gene therapy of human prostatic cancer.
AB  - This present study evaluates the potential of adenovirus-mediated gene transfer
      (AMGT) to the prostate of normal laboratory beagles. Many morphological and
      histological similarities can be noted between dog and human prostate. Moreover,
      dogs can spontaneously develop prostate cancer with a clinical and biological
      outcome identical to that in man. Firstly we showed the capacity of human
      adenovirus to infect canine prostatic cells in vitro. Secondly, we injected
      transrectally in the dogs' prostates 2x10(9) plaque forming units of a first
      generation recombinant adenovirus vector harboring the reporter gene beta
      galactosidase (AdRSVbetagal). Seven days after the adenoviral delivery, we
      observed expression of the transgene in both prostates, and exclusively in
      epithelial cells. Despite a cellular and a humoral immune response, the infusion
      appeared safe, since the dogs had no fever and presented no urinary symptoms.
      This study constitutes the first evaluation of AMGT in dog prostate and provides
      a basis for gene therapy treatment of prostate carcinoma-bearing patients.

PMID- 12496864
TI  - Influence of pertussis toxine on local progression and metastasis after
      orthotopic implantation of the human prostate cancer cell line PC3 in nude mice.
AB  - Tumor cell migration is a fundamental process of metastasis. Pertussis toxine
      inhibits lysophosphatidic acid related cell migration by ADP-ribosylation of G
      proteins. We examined the influence of pertussis toxine (PTX) on progression and
      metastasis of the human hormone-insensitive prostate cancer cell line PC-3 after
      orthotopic implantation in nude mice. In 30 athymic male nude mice (NMRI) 5x10(5)
      PC-3 cells were injected into the dorsal prostate. After 7 d 15 mice received a
      total of six intraperitoneal injections of 5 micro g PTX/100 g body weight at an
      interval of 4 d. The other 15 mice received phosphate buffered saline and served
      as control. All mice were killed at 37 d followed by macroscopical and
      histological evaluation of local tumor growth and metastasis. In the control
      group tumorigenicity was 100% (15 out of 15). Mean weight of the tumor bearing
      unit of prostate and seminal vesicles was 541 mg (243-763 mg). The rate of
      positive lymphnodes was 100% with a mean transversal diameter of 3.9 mm (1.2-5.4
      mm). In the PTX group local take rate was 100% with a mean weight of 251 mg (88
      478 mg) (P two sided <0.0001). The rate of positive lymphnodes was 60% (9 out of
      15) (P=0.017) with a mean transversal diameter of 2.3 mm (1.0-4.5 mm). PTX
      following orthotopic implantation of the human hormone-insensitive PC-3 cell line
      significantly reduces local tumor growth as well as metastasis to locoregional
      lymphnodes.

PMID- 12496865
TI  - The microtubule-stabilizing agents epothilones A and B and their desoxy
      derivatives induce mitotic arrest and apoptosis in human prostate cancer cells.
AB  - Epothilones are a new class of natural products that bind to tubulin and prevent
      the depolymerization of microtubules, although they have no structural similarity
      to paclitaxel. Taxanes are only marginally effective in the treatment of
      disseminated prostate cancer, although they may have useful activity when
      administered in combination with estramustine. Unlike paclitaxel, epothilones are
      not substrates for P-glycoprotein and are active in multidrug resistant cells.
      Epothilones A and B (EA, EB) have recently been synthesized in toto. In this
      report, we examine the effects of synthetic epothilones and their desoxy
      derivatives, as well as paclitaxel, on prostate cancer cell lines. EB was the
      most active of these compounds in tissue culture (IC(50): 50-75 pM), four to ten
      fold more potent than paclitaxel. EA and the desoxyderivatives of EA and EB (dEA,
      dEB) were also active, but less potent than EB. Each of these compounds causes
      mitotic block followed by apoptotic cell death. The relative potencies for cell
      cycle arrest and cytotoxicity directly correlate with the ability of the drugs to
      bind microtubules, stabilize mitotic spindles and induce the formation of
      interphase microtubule bundles. Therefore, synthetic epothilones are potent
      inhibitors of prostate cancer cell lines and work in a fashion similar to
      paclitaxel. Recently, we showed that farnesyl transferase inhibitors sensitize
      tumor cells to paclitaxel-induced mitotic arrest. We now have extended these
      observations to show that paclitaxel and the epothilones synergize with FTI to
      arrest the growth of prostate cancer cells. Moreover, this occurs in DU145, a
      cell line that is not particularly sensitive to the FTI. The combination of FTI
      and epothilone represent a new potential clinical strategy for the treatment of
      advanced prostatic cancer.

PMID- 12496867
TI  - What's hot in the prostate?

PMID- 12496868
TI  - Editorial.

PMID- 12496869
TI  - Intermittent androgen suppression for prostate cancer: rationale and clinical
      experience.
AB  - Research on hormonal treatments of prostate cancer over the past 20 y have
      focused on maximizing androgen ablation through combination therapy. Maximal
      androgen ablation increases treatment-related side-effects and expense and fails
      to prolong time to androgen-independent (AI) progression. The rationale behind
      intermittent androgen suppression (IAS) is based on: (1) observations that
      androgen ablation is palliative, not curative in most patients where quality of
      life must be considered; (2) assumption that immediate androgen ablation is
      superior to delayed therapy in improving survival of patients with prostate
      cancer; and (3) the hypothesis that if tumor cells which survive androgen
      withdrawal are forced into a normal pathway of differentiation by androgen
      replacement, then apoptotic potential might be restored and progression to
      androgen independence may be delayed. Observations from animal model studies
      suggest that progression to androgen-independence involves adaptive responses to
      androgen deprivation which are, in turn, modulated by intermittent androgen
      replacement. Supported by these animal model observations, several centers have
      now tested the feasibility of IAS therapy in non-randomized groups of patients
      with prostate cancer using serum PSA as trigger points. Experimental and clinical
      data suggest that prostate cancer is amenable to control by IAS. IAS may offer
      clinicians an opportunity to improve quality of life in patients with prostate
      cancer by balancing the benefits of immediate androgen ablation (delayed
      progression and prolonged survival) while reducing treatment-related side effects
      and expense. Whether time to progression and survival is affected in a beneficial
      or adverse way is being studied in randomized, prospective protocols. The purpose
      of this article is to review the rationale behind IAS, compare observations from
      published series, and discuss potential indications and treatment strategies
      using IAS.

PMID- 12496870
TI  - Does a family history of prostate cancer result in more aggressive disease?

PMID- 12496871
TI  - Use of multivariate models to improve prediction of pathologic stage for men with
      clinically localized prostate cancer.
AB  - To benefit from definitive local therapy, men with clinically localized prostate
      cancer should have organ-confined disease. We discuss the use of multivariate
      analysis using serum PSA, biopsy Gleason score and clinical stage to improve the
      prediction of pathologic stage. Serum PSA, biopsy Gleason scores and clinical
      stage correlate with pathologic stage by univariate analysis are used in this
      study. However, each of these variables cannot accurately predict stage for the
      individual patient. Several investigators have proposed clinical algorithms based
      on multivariate analysis to enhance pretreatment staging. For men with clinically
      localized prostate cancer, multivariate algorithms are useful to determine the
      probability of a man having organ-confined disease, seminal vesicle invasion and
      lymph node involvement. This information will better enable clinicians and
      patients to make informed decisions about appropriate treatment options.

PMID- 12496872
TI  - Receptor affinity and potency of non-steroidal antiandrogens: translation of
      preclinical findings into clinical activity.
AB  - The non-steroidal antiandrogens flutamide (Eulexin((R))), nilutamide
      (Anandron((R))) and bicalutamide (Casodex((R))) are widely used in the treatment
      of advanced prostate cancer, particularly in combination with castration. The
      naturally occurring ligand 5alpha-DHT has higher binding affinity at the androgen
      receptor than the non-steroidal antiandrogens. Bicalutamide has an affinity two
      to four times higher than 2-hydroxyflutamide, the active metabolite of flutamide,
      and around two times higher than nilutamide for wild-type rat and human prostate
      androgen receptors. Animal studies have indicated that bicalutamide also exhibits
      greater potency in reducing seminal vesicle and ventral prostate weights and
      inhibiting prostate tumour growth than flutamide. Although preclinical data can
      give an indication of the likely clinical activity, clinical studies are required
      to determine effective, well-tolerated dosing regimens. As components of combined
      androgen blockade (CAB), controlled studies have shown survival benefits of
      flutamide plus a luteinising hormone-releasing hormone analogue (LHRH-A) over
      LHRH-A alone, and for nilutamide plus orchiectomy over orchiectomy alone. Other
      studies have failed to show such survival benefits, including those comparing
      flutamide plus orchiectomy with orchiectomy alone, and nilutamide plus LHRH-A
      with LHRH-A alone. In a direct comparative study, bicalutamide (50 mg, once
      daily) was compared with flutamide (250 mg, three times daily), each in
      combination with an LHRH-A. Both therapies were well tolerated, although more
      patients could not tolerate flutamide therapy: 25 flutamide plus LHRH-A and 2
      bicalutamide plus LHRH-A patients withdrew from therapy due to diarrhoea. There
      were no statistically significant differences for time to progression or survival
      between the two antiandrogens. This clinical trial of bicalutamide confirms the
      prediction from preclinical studies that a 50 mg dose of bicalutamide would be
      appropriate for use in patients with advanced prostate cancer, and demonstrates
      that this bicalutamide dose is clinically effective when administered as part of
      CAB.

PMID- 12496873
TI  - Patterns of care for metastatic carcinoma of the prostate gland: results of the
      American College of Surgeons' patient care evaluation study.
AB  - The annual incidence of prostate cancer more than doubled between 1984 and 1990,
      increasing from an estimated 76 000-200 000 cases respectively. Part of this
      increase may have been the result of increased detection. This study utilizes
      data from an American College of Surgeons Patient Care Evaluation (PCE) study to
      report on changes in the management of metastatic disease. Approximately 2000
      hospitals were invited to submit data on a standard collection form designed by a
      multidisciplinary committee of specialists. Data were received from 730 hospitals
      on 14 716 patients with newly diagnosed cancer of the prostate in 1984, and from
      1035 hospitals for 23 214 patients in 1990. Between 1984 and 1990 there was a
      decrease in the percentage of reported patients diagnosed with Stage IV disease,
      falling from 25.3-21.2%. The number of patients receiving a prostate specific
      antigen (PSA) test increased from 6.3-74.8% and the proportion of abnormal PSA
      results increased from 82-92.7%. The proportion of patients diagnosed by
      transurethral resection of the prostate (TURP) and perineal biopsy decreased,
      while an increase was noted in the proportion of men diagnosed by transrectal
      biopsy and transrectal ultrasound (TRUS). Treatment by orchiectomy alone
      increased from 31.8-40.7% of patients, while the administration of exogenous
      hormone therapy alone declined from 22.3-14.9% of patients. Two and five-year
      survival rates for the most common forms of therapy were 56.7% and 22.5%
      respectively for orchiectomy, 57% and 24.6% respectively for exogenous hormone
      therapy, and 50.3% and 23.5% respectively for no cancer directed therapy.
      Following a second course of therapy, the two-year survival rate for patients
      receiving a subsequent orchiectomy was 36.7 vs 17.8% for those receiving
      secondary exogenous hormone therapy. The percentage of patients diagnosed with
      Stage IV disease has decreased while prostate cancer diagnoses are being made
      more frequently utilizing the PSA test and TRUS biopsies. Hormone treatment
      remains the most common form of therapy with either orchiectomy or exogenous
      hormone therapy having higher survival rates than other common treatment
      modalities.

PMID- 12496874
TI  - Adjuvant radiation therapy for recurrent PSA after radical prostatectomy in T1-T2
      prostate cancer.
AB  - To evaluate retrospectively the efficacy of adjuvant radiation therapy (ART) in
      patients with T1-T2 prostate cancer (CaP) in whom extracapsular cancer (pT3) was
      detected after radical prostatectomy (RP), together with biochemical failure
      characterized by a recurrent level of serum prostate-specific antigen (PSA)>0.1
      ng/mL. Twenty-two patients with T1-T2 CaP treated by RP who subsequently were
      found to have pT3 CaP with (13) or without (9) positive surgical margins and/or
      seminal vesicle invasion, exhibited biochemical failure characterized by a
      recurrent level of serum PSA, 2-40 (mean: 25) months after RP and were treated
      with ART (65 Gy). Bone and CT scans were negative in every patient, 15 of whom
      were submitted to TRUS biopsy (Bx) of the anastomosis (resection site), which was
      positive in 8. Patients were followed up for between 6 and 60 (mean: 32.5)
      months. Transient side effects (urgency, proctitis, diarrhea) were experienced by
      9 patients after ART. A decrease in serum PSA was observed in 19 patients;
      however, only 14 of these achieved an undetectable level (<0.1 ng/mL) on one or
      more occasions after completion of ART (in 12 cases this was after 3 months). Of
      the 14 patients, 8 achieved a persistently unmeasurable PSA level at a mean
      follow-up of 20.4 (range: 9-48) months. There was no difference between patients
      in whom an undetectable level of serum PSA was attained and those in whom it was
      not, with regard to specimen pathology, PSA doubling time, timing of ART, and the
      result of Bx. Patients who achieved an undetectable PSA had a lower mean PSA at
      the time of ART (1.1 vs 2.9 ng/mL, P<0.05) and a lower preoperative mean PSA.
      Although ART for biochemical failure after RP may lead to undetectable PSA levels
      in a significant proportion of patients for a significant period of time, a
      longer follow-up shows that such unmeasurable levels persist in only 36.4% of
      such patients.

PMID- 12496875
TI  - A comparison of three free and total PSA assays.
AB  - Prostate-specific antigen (PSA) has emerged as the most predictive test of
      whether or not a man has prostatic carcinoma. The free to total PSA ratio
      provides important enhancement in specificity, thus obviating unnecessary
      negative biopsies. In the absence of an international standard for total PSA,
      much less free PSA, variation between manufacturers may cause confusing results.
      We sought to compare three different manufacturer's free and total PSA assays in
      a population consisting of consecutive patients who had PSA testing in a
      reference laboratory in Germany. Between April 1994 and July 1996, serum
      specimens from 240 men were evaluated with three different free and total PSA
      assays. Indications for PSA determination were based on the referring physician,
      who also provided the clinical diagnosis. Total and free PSA were measured on the
      same freeze-thaw cycle with Chiron Diagnostics, Enzymun Boehringer Mannheim, and
      Hybritech Tandem-R assays. Seventy-nine men had carcinoma of the prostate, 120
      had clinical evidence of benign prostatic hyperplasia and 27 were without
      evidence of prostatic disease. The Chiron ACS: 180 free to total ratio compared
      very well with the Tandem-R assay at the 95% sensitivity level, affording 17 and
      22% specificity respectively. Using the range of total PSA of 4-10 ng/ml, the
      increase in specificity of the free to total PSA is quite significant, and the
      specificity of the Enzymun assays is greatly improved. (Specificity of 49%, 29%
      and 25% at 95% sensitivity for ACS, Enzymun and Tandem respectively.) This data,
      based on 'real world' clinical experience, shows significant variation between
      different manufacturers' assays. There was significant equivalence between the
      Chiron and Hybritech assays. The Enzymun assay performed well only when data from
      the total PSA range of 4-10 ng/ml was included. Clinicians must be aware of which
      manufacturers' assays for both the free and total PSA their laboratory staff is
      utilizing, and laboratory technicians must provide meaningful outcome data based
      on the patient population they serve with respect to the performance of these
      assays.

PMID- 12496878
TI  - Keyword Index to Volume 1.

PMID- 12496876
TI  - Comparison of tamsulosin efficacy in subgroups of patients with lower urinary
      tract symptoms.
AB  - We have compared the results of treatment with tamsulosin (0.4 mg once daily) in
      subgroups of patients with lower urinary tract symptoms suggestive of benign
      prostatic obstruction, based on two large-scale, open-label, observational
      studies. Improvements of IPSS or Q(max) were largely unaffected by patient age.
      Patients with severe symptoms benefited at least as much from treatment as those
      with mild or moderate symptoms, and the majority of patients with severe symptoms
      were shifted to the moderate or even mild symptoms group. We conclude that
      tamsulosin is effective in patients of all age groups, and should be considered
      as an alternative to surgery even in patients with severe symptoms.

PMID- 12496879
TI  - What's hot in the prostate?

PMID- 12496880
TI  - PCPD editorial.

PMID- 12496881
TI  - Health-related quality of life in men with prostate cancer.

PMID- 12496882
TI  - Neurotrophic factors in prostate and prostatic cancer.
AB  - Recent progress in growth factor research has led to a reexamination of the
      involvement of neurotrophic factors outside their classical domain of the nervous
      system. These last few years have seen a substantial accumulation of data
      concerning Nerve Growth Factor (NGF)'s prevalence within the prostate. NGF and
      its receptors were reported from the normal prostatic tissue, benign hyperplasia
      and prostatic cancer. Divergent ideas about the biological role of this factor,
      its specific distribution pattern within the tissue and its implication in the
      progression of carcinogenesis have been proposed. Especially the role of NGF in
      the metastatic process bears direct clinical relevance for research in this area.
      Many questions remain to be solved like the one on the prevalence of other
      neurotrophic factors. It is now increasingly becoming clear that neurotrophic
      factors do play a role in normal physiology and pathology of prostatic cells,
      opening up new prospects for diagnosis and treatment.

PMID- 12496883
TI  - Preoperative and operative factors to predict incontinence, impotence and
      stricture after radical prostatectomy.
AB  - The purpose of this study was to determine the incidence of patient-self reported
      post prostatectomy incontinence, impotence, bladder neck contracture or
      stricture, better, same or worse quality of life and willingness for same
      treatment again in a large group of radical prostatectomy (RP) patients and to
      determine if these morbidities are predictable with demographic, surgical or
      prostate cancer (PC) factors. Methods: A patient self-reporting questionnaire was
      completed and returned by 374 out of 458 eligible (81.7%) RP patients from one
      center, 267 (72.2%) have been operated since 1990 and all of whom were a minimum
      six month postoperative (75%>1 y). Questionnaire results were independently
      analyzed by a third party and correlated to demographic, operative, and tumor
      factors in an ongoing comprehensive PC database. Results: The patient self
      reported incidence of post prostatectomy incontinence (any degree), impotence,
      and bladder neck contracture or stricture was 72.2, 87.4, and 25.9%,
      respectively. The reported rate of incontinence requiring protection was 39.0%
      and only 2.4% had persistent bladder neck contracture/stricture. Pathologic stage
      (continuous variable) was the only factor to significantly predict incontinence
      and no factor could predict impotence or bladder neck contracture/stricture in
      univariate analysis. No factor was predictive of morbidity by multivariate
      analysis. Despite incontinence and impotence significantly affecting QOL self
      reporting (P=0.001, 0.001, respectively) and willingness to undergo RP again
      (P=0.001, 0.067, respectively), the majority of patients would choose surgery
      again. Conclusions: Although radical prostatectomy morbidity is common and
      affects patient-reported overall QOL, most patients would choose the same
      treatment again. Demographic, preoperative, operative, and tumor factors did not
      reliably predict patient-reported morbidity in this series.

PMID- 12496884
TI  - Characterization of prostate size, PSA and endocrine profiles in patients with
      spinal cord injuries.
AB  - Aims of this study: From cross-sectional and longitudinal population based
      studies as well as from autopsy studies it is well documented that total prostate
      volume increases with advancing age. However, it is not well known (1) which
      factors are ultimately responsible for this growth phenomenon; or (2) at what
      time in a persons life the growth tends to occur. At present at least a
      permissive role for testicular androgens is assumed to be involved in growth
      regulation. Other factors such as growth factors, epithelial-mesenchymal
      interaction, and the role of intact neural pathways are still poorly understood.
      We aimed to study a group of men with spinal cord injuries to determine whether
      the pattern of prostate enlargement would be different in men with partially or
      completely interrupted innervation of the pelvis and the prostate gland.
      Materials and methods: Forty-three men from the Spinal Cord Injury (SCI) Service
      at the VA North Texas Health Care System ranging in age from 27-73 y (mean 51 y)
      were recruited to participate in this study. Time since SCI ranged from 2-47
      (mean 19 y). All patients underwent standardized questionnaire, physical
      examination, transrectal ultrasonography (TRUS) measurements of total and
      transition zone volume of the prostate, serum PSA, testosterone (T),
      dihydrotestosterone (DHT), FSH and LH measurements, some had TRUS guided biopsies
      taken. Results: By all the measured criteria there were no abnormalities
      regarding the pituitary-gonadal axis observed in these men. Testicular volume,
      serum T, DHT and LH were within normal ranges, and when the patients were
      stratified by age, no differences were identified. There was an age related
      increase in FSH which has been described in neurologically intact men. Serum PSA
      increased slightly with advancing age. While total (TPV) and transition zone
      (TZV) prostate volume increased with age, the groupwise differences by decades of
      life were not significant. Moreover, when compared to a group of community
      dwelling men without known prostatic diseases and a clinic cohort of men with
      BPH, TPV was substantially lower for each decade of life except for men in their
      40s, while TZV was substantially lower for men in their 60s. Conclusions: We
      observed normal age related changes regarding serum PSA and serum FSH without
      significant changes in other hormonal parameters. All parameters behaved
      consistent with changes described in neurologically intact populations. However,
      we did not observe the typical increase in TPV and TZV of the prostate as seen in
      population, autopsy and clinic patient studies. This interesting finding
      indicates that factors other than an intact pituitary-gonadal axis and male
      steroid hormones may be responsible for the normal age related growth of the
      prostate. Further studies in larger cohorts are needed to corroborate our
      findings.

PMID- 12496885
TI  - Prevalence and natural history of urinary symptoms in a longitudinal national
      prostate cancer screening (community-based) study.
AB  - The AUA Symptom score (AUASS) was administered for three consecutive years to
      participants in a national prostate cancer screening study. Although the
      prevalence symptom free (AUSS=0) individuals was very low (<7%) in this cohort of
      16 000 men, mean AUASS and proportion of men in the mild, moderate and severe
      categories are equivalent to community-based studies from around the world.
      Across all ages and races, AUASS drops after 12 months but returns to original
      levels at 24 months. No differences in AUASS were noted for race when adjusted
      for age. Age is most strongly correlated to the increase in AUASS and to the
      severity of urinary symptoms.

PMID- 12496886
TI  - Amphiregulin is expressed in primary cultures of prostate myofibroblasts,
      fibroblasts, epithelial cells, and in prostate tissue.
AB  - The effect and expression of amphiregulin, a growth factor of the EGF-system was
      investigated in prostate primary cell cultures and in human prostate tissue.
      Amphiregulin increases proliferation in primary cultures of prostate
      myofibroblasts grown in serum-free medium. Amphiregulin mRNA is expressed in high
      amounts in primary cell cultures of prostate myofibroblasts, fibroblasts,
      epithelial cells, and in samples of prostate tissue. The data are supported by
      Western-blotting of amphiregulin in prostate myofibroblasts. These data call for
      a refocus of the expression and effects of the EGF system in the prostate.

PMID- 12496887
TI  - Immunohistochemical BCL-2 and Ki-67 expression predict survival in prostate
      cancer patients followed expectantly.
AB  - The prognostic value of BCL-2 expression, solely and combined with Ki-67
      expression, was determined in prostate cancer patients followed expectantly.
      Furthermore, associations with well established prognostic markers were tested.
      Formalin fixed, paraffin-embedded tumour tissue obtained at diagnosis was
      immunohistochemically investigated in 221 patients with a 15 y median follow-up
      time. BCL-2 protein was expressed in 114 (52%) tumours and was significantly
      associated with tumour stage (P=0.01). The prognostic value of BCL-2 expression
      was significant, using both disease-specific (P=0.0015) and overall survival
      (P=0.005) as endpoint. Patients with a combined BCL-2 negative/Ki-67 'low' tumour
      had the most favourable prognosis. This combined BCL-2/Ki-67 variable was of
      independently prognostic value in both the entire population (P=0.0001) and in
      the clinically localized subpopulation (P=0.035).

PMID- 12496889
TI  - Corrigendum.

PMID- 12496888
TI  - Three-year prospective study of 3228 clinical BPH patients treated with alfuzosin
      in General Practice.
AB  - Objectives: To investigate (a) the magnitude and durability of symptom score
      reduction and HRQL score improvement (including sexual drive); (b) adverse
      outcomes; and (c) progression to acute urinary retention and prostate surgery up
      to three years of treatment with alfuzosin. Methods: Three thousand two hundred
      and twenty-eight BPH-patients out of 812 centers were included in a prospective
      three-year open-labelled study and treated with alfuzosin (immediate release
      formulation) at the recommended dosage. A symptom score (Boyarsky modified) and a
      20-item BPH specific HRQL score including three questions of sexuality
      (Urolife(TM) BPH QoL 20) were self-administered at baseline, 3, 6, 12, 18, 24,
      30, and 36 months. Results: Two thousand five hundred and seventy-nine patients
      (79.9%) completed the study at the end of three years. Symptom score was
      significantly reduced by 54% at 3 months and this reduction was maintained up to
      36 months (-48.4%); HRQL score was significantly improved by 45.4% at 12 months
      and this improvement was maintained up to 36 months (+43.4%). Alfuzosin was well
      tolerated: the quantitative and qualitative distribution of adverse events was
      similar to that previously observed in placebo-controlled studies
      (vertigo/dizziness: 2.1%). Adverse events accounted for 4.2% of the drop-outs.
      120 patients (3.7%) were operated on for BPH and nine patients (0.3%) experienced
      acute urinary retention. Conclusion: This medical outcomes study confirms the
      long-term safety profile of alfuzosin in the naturalistic conditions of general
      practice and highlights the need to measure HRQL in the context of patient's
      preferences.

PMID- 12496890
TI  - What's hot in the prostate? Edited by Arie Belldegrun.

PMID- 12496891
TI  - Breaking bad news.

PMID- 12496892
TI  - Prostate cancer and sexual function.
AB  - Erectile dysfunction is a condition affecting 1 in every 10 men. Although its
      occurrence is related to ageing, illness and its necessary therapy can play a
      major role. Prostate cancer can lead to erectile dysfunction both psychologically
      through depression and emotional distress, and physically through therapy for the
      disease. An international quality of life survey involving 401 patients with
      prostate cancer was conducted. The objectives of the study were to investigate
      the patients' understanding of the treatment options they received, to explore
      the importance of the patient-doctor communication in the treatment of prostate
      cancer and to see what effect treatment had on patient's sexual function. One of
      the main findings of the survey was that too little counselling or information on
      treatment options and their effects on sexual function was provided to patients.
      Patients themselves felt that psychosexual counselling, in particular, would be
      helpful. In addition, therapy for prostate cancer appears to have a significant
      impact on patients' lifestyle and also on their libido, sexual function and
      activity.

PMID- 12496893
TI  - Prostate brachytherapy.
AB  - In recent years there has been an increase in the number of centres, especially
      in the USA, using prostate brachytherapy as a means of treating localised
      prostate cancer. Several centres now have medium term follow up data of large
      numbers of patients treated with this technique suggesting that outcome in terms
      of tumour control may be comparable to patients treated surgically. This review
      summarises results from different brachytherapy series and outlines some of the
      possible advantages of this technique compared with current conventional
      treatments for localised prostate cancer.

PMID- 12496894
TI  - Gene therapy for prostate cancer.
AB  - The treatment options for the patient with advanced prostate cancer are limited.
      Due to the recent advances in the understanding of the molecular biology of
      prostate cancer, the easy accessibility of the gland for injection, and the
      availability of gene promoters that can provide tissue specific expression of
      therapeutic gene sequences, gene therapy for prostate cancer is rapidly
      advancing. Many potential approaches for prostate cancer gene therapy have been
      identified, with a few of these already entering Phase I clinical trials. This
      review will discuss the basis of prostate cancer gene therapy, look at the
      potential approaches, and will compare the different vectors that can be used to
      deliver the therapeutic genes to the prostate tumor.

PMID- 12496895
TI  - Prospective evaluation of percent free-PSA and complexed-PSA for early detection
      of prostate cancer.
AB  - Aims of the study: Retrospective studies investigating the use of percent free
      PSA for early detection of prostate cancer were limited for various reasons: by
      their use of long-term stored sera, poor mix of non-cancer to cancer cases and
      the use of only men with PSA values between 4.0 and 10.0 ng/mL. This prospective
      study investigates the clinical utility of percent free-PSA and complexed-PSA for
      early detection of prostate cancer in 219 consecutive men presenting for prostate
      biopsy. Methods: Of 246 consecutive men who underwent ultrasound guided sextant
      biopsy of the prostate for PSA elevation and/or suspicious digital rectal exam,
      219 men had serum total PSA levels between 2.0 and 20.0 ng/mL and were included
      in this study. Serum total, free and complexed (PSA-ACT) were measured (Hybritech
      Inc.). Results: Pathologic examinations demonstrated that 72% and 28% of the
      biopsies were non-cancer and cancer respectively. The mean percent free-PSA was
      statistically different between the groups (cancer 14%+/-6.4 and non-cancer 18+/
      9%, P<0.001) and improved cancer detection. PSA-ACT provided only modest
      improvement in cancer detection over that of total PSA. Among this cohort of men,
      the optimal total PSA reflex range for percent free-PSA was 3.0-7.0 ng/mL (38%
      specificity) with a percent free-PSA cut-off of 20% (95% sensitivity) yet only
      affected 56% of the cases. Conclusions: PSA-ACT added very little additional
      value to the clinical utility of total PSA for early detection. Percent free-PSA
      performed well for all reflex ranges. A sensitivity and specificity of 95% and
      20% respectively were obtained using a single cut-off of 25% for percent free-PSA
      for the group of men with total PSA values between 4.0 and 10.0 and correlated
      well with recently reported prospective analyses.

PMID- 12496896
TI  - Use of intravenous fosfestrol tetrasodium (Honvan) infusion in treatment of
      symptomatic advanced prostate cancer.
AB  - Fosfestrol tetrasodium (Honvan) is a synthetic oestrogen-based compound. Studies
      have suggested its use in the treatment of localised, advanced and hormone
      refractory prostate cancer. This series of 17 patients with advanced disease
      documents the response, both subjective and objective, to standard dose
      intravenous Honvan infusion. Infusions were well tolerated, with no
      cardiovascular side-effects. Twelve patients received Honvan as de novo therapy,
      of whom 10 (83%) described subjective improvement and 11 (92%) had objective
      evidence of improvement, 11 (92%) had documented falls in prostate-specific
      antigen (PSA) levels. Nine patients received Honvan infusions as secondary
      treatment for hormone-escaped disease (1 patient received Honvan for a second
      time and another for a second and third time). Of these, 1 (11%) had a documented
      fall in PSA; 3 (33%) reported a subjective symptomatic improvement, and 2 (22%)
      demonstrated objective evidence of improvement. Patients with symptoms from bulk
      abdomino-pelvic disease seemed to fare better than those with bony metastases.
      This may suggest a specific indication for Honvan in a subgroup of patients with
      acute obstructive events of the ureters, urethra or circulatory vessles, in
      particular its value as a de novo therapy. In those patients who received Honvan
      as secondary therapy, some response was seen in a third, but overall these
      patients remained hormone-refractory.

PMID- 12496897
TI  - A novel monoclonal antibody 107-1A4 with high prostate specificity: generation,
      characterization of antigen expression, and targeting of human prostate cancer
      xenografts.
AB  - Monoclonal antibodies with high specificity for prostate tissue are of interest
      for prostate cancer research and treatment. Reactivity and specificity of a new
      murine monoclonal antibody, 107-1A4, was assessed by immunohistochemistry, ELISA
      and indirect immunofluorescence (IDIF). 107-1A4 stained all normal and malignant
      prostate tissue specimens while reactivity to non-prostate tissue was limited to
      the tubules of the normal kidney and renal cell carcinoma. Twenty two human cell
      lines were included in the reactivity survey; only the immunogen prostate cancer
      line LNCaP reacted with 107-1A4. Seminal plasma proteins PSA, PAP, PSMA, and PSP
      94 were determined not to be the 107-1A4 antigen.

PMID- 12496898
TI  - Standard vs conformal radiation therapy for adenocarcinoma of the prostate: no
      difference.
AB  - Objective: To compare results of treatment of adenocardinoma of the prostate
      using Standard (2D) vs Conformal (3D) treatment planning. Methods: The records of
      all patients with adenocarcinoma of the prostate treated curatively with
      radiation therapy alone from July 1991 to June 1994 were reviewed. Acute and late
      complications were scored by the RTOG criteria. Biochemical failure was defined
      as a rising PSA of at least 10% on two measurements separated >/=1 month or
      either a PSA nadir >4 ng/ml or >1 ng/ml. Disease free survival (DFS) was defined
      as no evidence of local, distant, or biochemical failure. 2D planning included
      standard simulation with target volume drawn from the treatment planning or
      diagnostic CT. 3D planning included a CT in the treatment position with computer
      simulation using beam's-eye-view for field design. Results: Two-hundred and
      seventeen 2D and 45 3D patients had similar median age and pre-treatment PSA, T
      stage, and dose to the prostate. The median follow-up periods for the 2D and 3D
      groups were 32.0 and 21.5 months, respectively. The two-year actuarial survival,
      local or biochemical control, and DFS were not different. The 3D group had a
      significantly higher incidence of acute bladder side effects of all grades and
      acute grade 1/2 rectal complications. There were no differences in the incidence
      of late bladder or rectal complications. Conclusions: Careful 2D planning for the
      treatment of localized adenocarcinoma of the prostate is an acceptable means of
      treatment. Within the dose range of 64-70 Gy, this preliminary analysis
      demonstrated no reduction in complications nor improvement in local or
      biochemical control, or DFS was seen with the the use of 3D treatment planning.

PMID- 12496901
TI  - What's hot in the prostate?

PMID- 12496902
TI  - Unravelling the confusions in prostatic disease.

PMID- 12496903
TI  - Prostate cancer in African American men.

PMID- 12496904
TI  - Management of radiation failure for localized prostate cancer.
AB  - Due to the historically large number of patients with localized prostate cancer
      (CAP) treated by radiation therapy, an increasing number of patients are
      presenting local failure. The currently available concepts regarding its
      definition as well as management options are reviewed. The literature regarding
      radiation failure for localized prostate cancer was reviewed. Emphasis was made
      on articles concerning definition of radiation failure, patient evaluation and
      restaging and definitive as well as palliative management options. There is
      definitely a subset of patients with locally recurrent prostate cancer without
      evidence of metastasis that could potentially benefit from aggressive local
      therapy. A treatment algorithm is proposed but it should be emphasized that
      treatment options should be individualized to suit the need of a particular
      patient.

PMID- 12496905
TI  - Distress due to unwanted side-effects of prostate cancer treatment is related to
      impaired well-being (quality of life).
AB  - Based on traditional quality of life scales, it has been suggested that known
      side-effects of prostate cancer treatment do not influence the quality of life.
      The present authors have developed an alternative approach to quality of life
      assessment applying epidemiological methods. Using a self administered
      questionnaire, we investigated 431 prostate cancer patients and an age stratified
      sample of 435 randomly selected men. Patients reporting any level of distress due
      to waning sexual functions (66%) or urine or bowel symptoms (38%), reported a
      lower psychological well-being compared to patients not reporting these symptoms
      or patients not distressed by their symptoms. Our results stress that an intact
      sexual and urinary and bowel functions are important for the quality of life
      among elderly men with or without prostate cancer.

PMID- 12496906
TI  - Transitions in health-related quality of life during the first nine months after
      diagnosis with prostate cancer.
AB  - Health-Related Quality of Life (HRQOL) is an important outcome measure in the
      study of prostate cancer. There are few data regarding the effect of
      sociodemographic variables, such as insurance status, educational level, marital
      status or income, on HRQOL. We examined whether these or other sociodemographic
      and clinical variables are predictive of HRQOL outcomes using an observational
      database of prostate cancer patients accrued from a wide array of clinical
      practice settings. We studied 131 patients with newly-diagnosed prostate cancer
      who had been followed for at least nine months. Patients were enrolled in
      CaPSURE(TM), a large, observational database of patients with prostate cancer.
      General and disease-specific HRQOL were measured with established, validated
      instruments at diagnosis and nine months later. Sociodemographic data and co
      morbidity counts were recorded at baseline. Multivariate regression analysis was
      used to determine whether sociodemographic or clinical variables were predictive
      of baseline HRQOL or HRQOL changes during the study period. Several
      sociodemographic and clinical variables demonstrated significant associations
      with HRQOL. We found improvements in general and disease-specific domains of
      HRQOL during the nine months after diagnosis. For married patients, Emotional
      Well-Being and Family Functioning scores were better at baseline (+11.8, P<0.02),
      but Family Functioning declined over the nine month study period (-18.5,
      P=0.0006). Older patients had slightly better baseline performance in several
      domains of HRQOL, but experienced greater HRQOL decrements over time than did
      younger patients. Increasing comorbidity was associated with worse baseline
      general HRQOL. Early tumor stage was predictive of better scores in general HRQOL
      domains at baseline. Limited palpable disease stage (T2A/T2B) was predictive of
      worse Sexual Function and Sexual Bother at nine months (-8.6, P=0.04; -24,
      P=0.008). After initial decreases, patients appear to experience an improvement
      in general and disease-specific HRQOL within nine months of initial diagnosis
      with prostate cancer. Marital status is associated with better HRQOL, while
      advancing age is associated with more significant HRQOL declines over time.
      Patients with lower stage disease were noted to have better general HRQOL at
      baseline, although decreases in the physical domains were noted at nine months.
      These data shed new light on patients' experience with prostate cancer and
      suggest that HRQOL outcomes over time may occur in a predictable manner.

PMID- 12496907
TI  - Disease specific death after external beam radiation of prostate cancer.
AB  - Our purpose in this paper was to examine the association of age, race, stage,
      grade, and calendar period with and generate estimates of disease-specific
      mortality after external beam radiation for prostate cancer. Using data from the
      Surveillance Epidemiology and End Results Program, we fit proportional hazards
      models and used life table analyses to estimate survival distribution. High grade
      and stage, black race, and early calendar period were individually associated
      with disease-specific mortality. Disease-specific survival ranged from 43% for
      poorly differentiated regional cancer diagnosed in 1978-1982 to 88% for well
      differentiated localized cancer diagnosed in 1983-1987. Estimates of disease
      specific mortality varied by grade, stage and calendar period of diagnosis. These
      estimates may be considered in evaluating future treatments.

PMID- 12496908
TI  - The epidemic of prostate cancer and the medical literature: a causal association?
AB  - The diagnosis of prostate cancer has undergone an unprecedented recent increase,
      while mortality has increased much more slowly. We examined new prostate cancer
      diagnoses from 1987-1992 in a nationwide prospective cohort study of 51 529 men
      enrolled in the Health Professionals Follow-up Study, a population likely to be
      medically sophisticated and thus early to adopt medical innovations. The age
      adjusted incidence of prostate cancer rose approximately 2(1/2) fold during the
      study period. Nearly all of the increase occurred among organ-confined tumors,
      with a smaller increase for regionally-advanced tumors and none for metastatic
      tumors. Using a Poisson regression model of newly-diagnosed cancers, we found
      organ-confined cancers rose abruptly by 86% (95% CI: 36-256%; P=0.0001) and
      regionally-advanced tumors by 73% (95% CI:12-267%; P=0.01) after March, 1991,
      when a study advocating screening using the prostate specific antigen (PSA) was
      published in the New England Journal of Medicine. The recent increase in the
      incidence of prostate cancer is probably due to the increased PSA screening of
      asymptomatic men, resulting in the diagnosis of large numbers of men with early
      stage disease from 1990 onward. Despite ongoing debate over the value of PSA
      screening, the rate of diagnosis accelerated sharply after the publication of a
      well-publicized but inconclusive study advocating screening. In a context of
      growing disease awareness, well-publicized research reports may result in
      unexpectedly amplified acceptance into medical practice.

PMID- 12496909
TI  - Haematuria associated with BPH-Natural history and a new treatment option.
AB  - Bleeding of prostatic origin is usually caused by the friable hypervascularity of
      the prostate, the vessels of which are easily disrupted by physical activity. The
      condition is often ignored after the patient has been fully investigated and more
      serious causes for bleeding excluded and treatment is often withheld unless the
      bleeding becomes excessive. We analysed the clinical effect of finasteride in the
      treatment of this condition. We retrospectively reviewed 42 patients diagnosed as
      having haematuria secondary to bleeding from a benign prostate. Eighteen patients
      were simply reassured and given no treatment. Twenty-four patients with prostatic
      bleeding were treated using finasteride. All case notes were reviewed and the
      patients were contacted by telephone. Of 18 patients who had prostatic bleeding
      but did not receive treatment the mean age was 70 y and the mean follow-up was 10
      months; two had died, nine had no further bleeding, two had a single episode of
      bleeding requiring no treatment, six had several bleeding episodes of whom one
      started finasteride, one refused treatment, and three required TURP. In the group
      treated with finasteride the mean follow up was 9 months, the mean age of the
      patients was 75 y. Twenty patients had no further bleeding, one patient
      experienced minor intermittent bleed and required no further treatment. Two
      patients died of non-urological causes, one patient stopped the treatment because
      of impotence and one patient had mild gynecomastia. Haematuria secondary to
      prostatic bleeding can be significant if not treated. Finasteride appears to be
      effective in suppressing haematuria caused by benign prostatic hyperplasia and
      should be considered in treating this problem.

PMID- 12496910
TI  - Components of the metabolic syndrome-risk factors for the development of benign
      prostatic hyperplasia.
AB  - The purpose of the present study was to perform a BPH risk factor analysis in
      men, relating the prostate gland volume to components of the metabolic syndrome
      and to identify clues to the etiology of BPH. Our material comprised a
      consecutive series of 158 patients with lower urinary tract symptoms with or
      without manifestations of the metabolic syndrome. In this group, the measured
      volume of the prostate was related consecutively to potential risk factors. The
      diagnoses atherosclerosis, non-insulin-dependent diabetes mellitus (NIDDM) and
      treated hypertension were obtained from the patient's medical history. Data on
      blood pressure, waist and hip measure, body height and weight were collected and
      body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples
      were drawn from fasting patients to determine insulin, cholesterol,
      triglycerides, HDL and LDL-cholesterol, uric acid and ALAT. The prostate gland
      volume was determined using ultrasound. Our results show that there was a larger
      prostate gland in men with NIDDM (P=0.0058), treated hypertension (P=0.0317),
      obesity (P<0.0001), low HDL-cholesterol levels (P=0.0132) and high insulin levels
      (P<0.0001) than in men without these conditions. The prostate gland volume
      correlated positively with the systolic blood pressure (r(s)=0.17; P=0.03),
      obesity (r(s)=0.34; P<0.0001) and fasting insulin (r(s)=0.38; P<0.0001) and
      negatively with HDL-cholesterol (r(s)=-0.22; P=0.009). On the basis of our
      findings, we concluded that NIDDM, treated hypertension, obesity, low HDL
      cholesterol levels and high insulin levels constitute risk factors for the
      development of BPH. The results suggest that BPH is a facet of the metabolic
      syndrome and that BPH patients may share the same metabolic abnormality of a
      defective insulin-mediated glucose uptake and secondary hyperinsulinemia as
      patients with the metabolic syndrome. The findings generate a hypothesis of a
      causal relationship between high insulin levels and the development of BPH. In a
      clinical setting, the findings of the present report suggest that, in any patient
      presenting with BPH, the possible presence of NIDDM, hypertension, obesity, high
      insulin and low HDL-cholesterol levels should be considered. Conversely, in
      patients suffering from these conditions, the possibility of a clinically
      important BPH should be kept in mind.

PMID- 12496912
TI  - Biopsy Pathology of the Prostate.

PMID- 12496911
TI  - Morning vs evening dosing with doxazosin in benign prostatic hyperplasia:
      efficacy and safety.
AB  - Three hundred and fifty-three patients with symptomatic benign prostatic
      hyperplasia were randomized to doxazosin or placebo, with morning or evening
      dosing, to compare the effect of dosing time on the efficacy and safety of
      doxazosin treatment. After 24 weeks of treatment, the mean International Prostate
      Symptom Score had decreased by 6.8 units in the doxazosin group compared with 4.5
      units in the placebo group (P=0.003). Improvements in Q(max) of 2.03 ml/s and
      0.30 ml/s were seen for the doxazosin and the placebo groups, respectively
      (P<0.001). No differences in efficacy or safety between the morning- and evening
      dosed subgroups were observed. Doxazosin was significantly more effective than
      placebo at improving symptoms of BPH and urinary flow rates at endpoint, and was
      well tolerated. The time of dosing did not appear to influence the efficacy or
      safety of doxazosin, suggesting that there is no need to restrict administration
      of doxazosin to the evening in BPH patients.

PMID- 12496913
TI  - What's hot in the prostate?

PMID- 12496914
TI  - Editorial.

PMID- 12496915
TI  - CaPCURE's fourth meeting: the cutting edge of current prostate cancer research.

PMID- 12496916
TI  - Prostate Biopsy in the staging of prostate cancer.
AB  - The use of prostate biopsies was developed in parallel with progress in our
      knowledge of prostate cancer and the use of prostate-specific antigen (PSA).
      Prostate biopsies were initially indicated for the diagnosis of cancer, by the
      perineal approach under general anesthesia. Nowadays prostate biopsies are not
      only for diagnostic purposes but also to determine the prognosis, particularly
      before radical prostatectomy. They are performed in patients with elevated PSA
      levels, by the endorectal approach, sometimes under local anesthesia. The gold
      standard is the sextant biopsy technique described by Hodge, which is best to
      diagnose prostate cancer, particularly in case of T1c disease (patients with
      serum PSA elevation). Patients with a strong suspicion of prostate cancer from a
      negative series of biopsies can undergo a second series with transition zone
      biopsy or lateral biopsy. Karakiewicz et al and Uzzo et al proposed that the
      number of prostate biopsies should depend on prostate volume to improve the
      positivity rate. After the diagnosis of prostate cancer, initial therapy will
      depend on several prognostic factors. In the case of radical prostatectomy, the
      results of sextant biopsy provide a wealth of information. The aim of this report
      is to present the information given by prostate biopsy in the staging of prostate
      cancer.

PMID- 12496917
TI  - Conservative management of clinically localized prostate cancer.
AB  - The purpose of this paper is to review and summarize the current knowledge on
      conservative management of localized prostate cancer. Deferring treatment for low
      grade, clinically localized prostate cancer is an acceptable treatment option for
      patients with a life expectancy of 10-15 y or less. The outcome of available
      studies on deferred treatment in selected series cannot be compared with the
      outcome in register studies where the patients have been managed with noncurative
      intent, nor can it be directly compared with the outcome of selected series on
      other treatments. The outcome of different treatments for localized prostate
      cancer can only be compared in randomized studies.

PMID- 12496918
TI  - Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in late
      pathological stage human prostate cancer.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme best
      known to many investigators as a 'housekeeping' gene used as a loading control on
      northern blots. Prior studies, however, have shown that GAPDH RNA levels vary
      greatly among different prostate cancer cell lines. We undertook this study to
      determine the level of GAPDH gene expression within primary human prostate tumors
      and to determine the validity of using GAPDH as a loading control for northern
      analysis of human prostate cancer specimens and normal human organs. We found
      that GAPDH expression was significantly higher in specimens from patients with
      pathological stage C and D prostate cancer than those with stage B disease.
      Within the human prostate cancer cell lines TSUPr1, DU145, LNCaP and PC-3 and a
      normal neonatal prostate epithelial cell line FNC 267beta1, LNCaP cells expressed
      the highest level of GAPDH but all cell lines, including the normal neonate
      prostate cell line had very strong GAPDH gene expression. GAPDH RNA levels were
      highly variable among 16 normal human adult organs and four human fetal organs
      examined. We conclude that GAPDH RNA levels in human prostate tumors correlate
      with pathologic stage and that GAPDH should not be used as a loading control in
      northern blot experiments. Other controls, such as beta-actin or 28s ribosomal
      RNA, would be more suitable for such purposes.

PMID- 12496919
TI  - A cross-sectional study of vasectomy, time since vasectomy and prostate cancer.
AB  - Past studies of the association of vasectomy and prostate cancer have reported
      inconsistent results. Our objective was to investigate whether vasectomy and time
      since vasectomy are associated with a higher risk of prostate cancer. We
      conducted a cross-sectional study on unduplicated records of >95 000 participants
      in a longitudinal study (1993-1995) of prostate cancer screening conducted during
      Prostate Cancer Awareness Week. Vasectomy was reported by 28%, and there were
      2530 biopsies. (chi)(2) tests and logistic regression analyses were used and
      found that vasectomy and an increased length of time since vasectomy are not
      associated with a higher risk of prostate cancer.

PMID- 12496920
TI  - Prevalence of prostatic intra-epithelial neoplasia (PIN) in biopsies from
      hospital practice and pilot screening: clinical implications.
AB  - As high grade PIN is commonly associated with concomitant cancer, current
      literature recommends re-biopsy of patients with high grade PIN. This paper
      describes the prevalence of high grade prostatic intra-epithelial neoplasia (PIN)
      from three independent clinical settings, reported by a single pathologist (MCP).
      High grade PIN was diagnosed in biopsies from 131 of the 1205 (11%) of patients
      in whom cancer was suspected in hospital practice, 42 of the 202 (20%)
      asymptomatic men screened for prostate cancer and 29 of the 118 (25%) patients
      presenting with prostatism in a case finding study. Re-biopsy on this scale has
      major clinical and cost implications. However, from a literature review, there is
      evidence to suggest that the risk of concomitant cancer with high grade PIN may
      be stratified according to serum PSA. This opinion should be tested
      prospectively.

PMID- 12496921
TI  - Doxazosin in the treatment of benign prostatic hyperplasia. A review of the
      safety profile in older patients.
AB  - The objective of this paper is to review the safety of doxazosin in older
      patients (>/=65 y) with benign prostatic hyperplasia (BPH) as reported in seven
      international clinical trials. Data from seven double-blind, placebo-controlled,
      phase III trials, in both normotensive and hypertensive patients with BPH were
      collated and analysed. Data on doxazosin were available for 341 men 65 y and
      over. Even though older patients can be at particular risk of adverse drug
      reactions, there was no apparent evidence of poor tolerability with doxazosin in
      older patients with BPH. The percentages of younger normotensive BPH patients
      (<65 y) experiencing at least one adverse event were 47 and 44% for doxazosin and
      placebo groups, respectively; for older normotensive BPH patients (>/=65 y) the
      corresponding values were 42 and 38%. For the younger hypertensive BPH patients
      the incidence rates for adverse events were 55% (doxazosin) and 42% (placebo) and
      for older hypertensive BPH patients 43 and 30%, respectively. The most commonly
      reported adverse events for all groups were dizziness, headache and fatigue and
      few serious adverse effects were reported throughout these trials. It can be
      concluded that doxazosin is well tolerated in young and old, normotensive and
      hypertensive patients with BPH.

PMID- 12496922
TI  - Day to day changes in free and total PSA: significance of biological variation.
AB  - In this study we evaluated the physiological variation of free and total prostate
      specific antigen (PSA) levels to determine how the percent free/total PSA was
      affected. Twenty four patients had blood drawn for ten consecutive weekdays. The
      percent coefficient of variation (%CV) of biological variation was calculated.
      The results were log-normally distributed with geometric means of 12.0% CV, 7.3%
      CV, and 8.8% CV for free, total, and percent free/total PSA, respectively. When
      applied, the percent free/total, PSA would need to fluctuate by 31% to indicate
      that a significant change (critical difference, P<0.05) between two measurements
      had occurred. Biological variation of PSA measurements is substantial.

PMID- 12496923
TI  - A multicentre prospective study of prostatic volume in asymptomatic men in
      various continents.
AB  - Objective: To compare prostatic volumes in asymptomatic Asian men with similar
      controls in Europe. Patients and methods: Six centres (Beijing, Hong Kong, Jinan,
      Lisbon, Palermo and Stirling) independently selected asymptomatic men aged 55 y
      or more for assessment of prostatic volume using transrectal ultrasound
      (total=320 men) between 1992 and 1993. Results: Prostatic volumes in asymptomatic
      men were greater in Beijing than Hong Kong, Stirling and Palermo (P<0.05) and
      were smaller in Stirling than Beijing and Jinan (P<0.05). Conclusions: These
      results suggest that men from Stirling are less likely to have large prostates,
      but there is no evidence that men from any of the six cities are more likely to
      have small prostates. This small series may suggest that benign prostatic
      hyperplasia (BPH) is as common in China as in European cities. The differences
      may be due to some cities (Beijing, Jinan and Lisbon) having a greater proportion
      of high values, perhaps suggesting looser selection criteria. This may indicate
      an abandonment of traditional Asian foods with their presumptive beneficial
      effect in favour of a Western dietary style.

PMID- 12496924
TI  - Low molecular weight heparin and radical prostatectomy: a prospective analysis of
      safety and side effects.
AB  - We prospectively analyzed the safety of the perioperative use of low molecular
      weight heparin (LMWH) for prophylaxis of thromboembolic complications after
      radical retropubic prostatectomy (RRP). Seventy-three consecutive patients
      received Enoxaparin, a LMWH compound one hour before RRP and then every twelve
      hours until hospital discharge. A mean of seven doses of LMWH were administered.
      A comparison was made with a control group of eighty-nine patients undergoing RRP
      without anticoagulant prophylaxis. Estimated blood loss was 515+/-215 cc with
      LMWH patients and 611+/-471 cc in controls. Total drain output was a mean of 318
      cc with LMWH and 300 cc in controls. Seven percent of patients treated with
      enoxaparin developed a wound or operative site hematoma or lymphocele compared
      with none in the control group. LMWH appears to be a relatively safe means of
      prophylaxis for thrombo-embolic complications after RRP with no apparent increase
      in intraoperative bleeding or postoperative drainage. However, postoperative
      hemorrhagic complications or lymphocele formation are slightly increased. LMWH
      should be considered for prophylaxis of thromboembolic complications in high risk
      individuals but the associated morbidity does not support its routine use.

PMID- 12496925
TI  - Editorial.

PMID- 12496926
TI  - Pre-treatment staging of prostate cancer: recent advances and future prospects.
AB  - No abstract

PMID- 12496927
TI  - MRC study: when to commence treatment in advanced prostate cancer.
AB  - No abstract

PMID- 12496928
TI  - Epitope mapping of human prostate specific antigen and glandular kallikrein
      expressed in insect cells.
AB  - Two human prostate gland proteases were expressed in insect cells using
      recombinant baculovirus expression system. Prostate specific antigen (PSA) is an
      established serum marker of prostate cancer whereas the clinical utility of its
      close homologue, human glandular kallikrein (hK2) is presently unknown. The
      production levels using Trichoplusia ni cells were roughly 300 &mgr;g/l and 6
      mg/l for hK2 and PSA, respectively. On western-blot we estimated the size for
      both proteins to be approximately 33 kDa which was consistent with PSA purified
      from seminal plasma. Nine anti-PSA monoclonal antibodies (Mabs) out of 26 tested,
      representing five independent epitopes, also reacted with hK2. The results
      obtained in this study may help in designing more accurate diagnostic assays for
      detection and monitoring of prostate cancer.

PMID- 12496929
TI  - Aneuploidy and rapid cell proliferation in recurrent prostate cancers with
      androgen receptor gene amplification.
AB  - Mechanisms of prostate cancer recurrence during androgen deprivation are poorly
      understood. We recently described androgen receptor (AR) gene amplification in
      28% of recurrent prostate carcinomas from hormone-refractory prostate cancer
      patients. To investigate the hypothesis that amplification of the AR gene
      promotes the growth of hormone-refractory prostate carcinomas, DNA flow
      cytometric (FCM) studies were carried out to compare matched, primary and hormone
      refractory recurrent samples from 31 prostate cancer patients. Recurrent tumours
      had a higher (P=0.05) S-phase fraction (SPF) (10.6+/-4.6) than corresponding
      primary tumours from the same patients (7.0+/-4.1) and the frequency of
      aneuploidy also increased from 8-55%. Recurrent tumours with AR gene
      amplification had a significantly higher (P=0.02) SPF (14.0+/-6.5) than those
      with no amplification (9.0+/-2.9). The results suggest that clinical progression
      of prostate cancer during androgen withdrawal therapy is often associated with
      increased cell proliferation rate and formation of DNA aneuploidy. AR
      amplification may be an important molecular mechanism underlying the increase in
      proliferation rate of some recurrent tumours.

PMID- 12496930
TI  - Combined analysis of two multicenter studies of finasteride 5 mg in the treatment
      of symptomatic benign prostatic hyperplasia.
AB  - The purpose of this paper is to examine effects of finasteride 5 mg across
      different age groups in an ethnically diverse population of men with symptomatic
      benign prostatic hyperplasia (BPH) seen in community urology and primary care
      practices. Data were combined from two previous placebo-controlled randomised
      trials of finasteride that evaluated changes in urinary symptoms, blinded global
      assessments of urologic status, adverse experiences, and effects on
      dihydrotestosterone (DHT) and prostate-specific antigen (PSA) in over 4500 men.
      Finasteride showed a favourable efficacy and tolerability profile in this large
      ethnically diverse population and was similarly effective in middle-aged and
      older men with BPH and prostate gland enlargement.

PMID- 12496931
TI  - Prognostic significance of angiogenesis in clinically localized prostate cancer
      (staining for Factor VIII-related antigen and CD34 Antigen.
AB  - Tumour angiogenesis is widely considered to be an important phenomenon in the
      process of tumour growth and metastasis. We investigated the prognostic
      significance of the microvascular count (MVC) in prostate cancer of each Gleason
      grade and compared the results to other established pathologic parameters and
      progression probability. We also compared the staining of Factor VIII-related
      antigen (FVIII-RA) with CD34 antigen (CD34 Ag) staining for determination of the
      MVC. We examined 101 radical prostatectomy specimens from patients who underwent
      curative therapy for clinically localized adenocarcinoma of the prostate as the
      first form of therapy. To identify microvessels, immunohistochemical staining of
      endothelial cells was performed using antibodies to FVIII-RA and CD34 Ag in
      formalin-fixed, paraffin-embedded tissue. Microvessels were counted in fivex200
      fields (0.785 mm(2) on each Gleason grade in the 'hot' areas. We used the highest
      number of five fields in the worst Gleason grade on each staining for statistical
      analysis. MVC using FVIII-RA and CD34 Ag staining correlated with pathologic
      stage, Gleason score and preoperative serum prostate-specific antigen level. In
      addition, MVC using CD34 Ag staining also correlated with DNA ploidy and total
      tumour volume. The Gleason score was found to be the best prognostic indicator
      using Cox proportional hazards regression analysis. In this study, MVC in
      prostate cancer was predictive of pathologic stage and Gleason grade, but MVC by
      either FVIII-RA and CD34 Ag staining was not an independent prognostic predictor.
      The best prognostic indicator in this study was Gleason score.

PMID- 12496932
TI  - The relation of p53 protein nuclear accumulation and angiogenesis in human
      prostatic carcinoma.
AB  - All neoplasms require angiogenesis and resulting neovascularity for growth beyond
      1 mm(2). Quantitative microvessel density (MVD) has been shown to provide staging
      and prognostic significance in human prostate cancer (CaP). recently, it has been
      demonstrated that loss of the wild-type allele of the p53 tumour suppressor gene
      results in reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of
      angiogenesis. There is also an increased expression of vascular endothelial
      growth factor which promotes neovascularization. p53 gene mutation and MVD were
      investigated in men with prostate cancer. Sections from 103 radical prostatectomy
      cases were evaluated with immunohistochemistry to detect mutant p53 proteins.
      Quantitative MVD was performed on the cases exhibiting p53 positive staining and
      compared with negative fields of similar Gleason grade on the same histologic
      sections. Twenty of the 103 cases (19.4%) revealed positive p53 staining nuclei.
      In 19 of these 20 cases, the MVD in p53 positive areas was greater than
      corresponding control regions (overall P<0.0001). Extent of p53 abnormality, as
      well as MVD, correlated with pathologic stage. These data suggest that mutations
      of the p53 tumour suppressor gene may be associated with increased angiogenesis
      in CaP. In addition to providing staging and prognostic information, this
      relationship potentially has therapeutic implications.

PMID- 12496933
TI  - Structural dynamics of individual Holliday junctions.
AB  - The four-way DNA (Holliday) junction is the central intermediate of genetic
      recombination, but the dynamic aspects of this important structure are presently
      unclear. Although transitions between alternative stacking conformers have been
      predicted, conventional kinetic studies are precluded by the inability to
      synchronize the junction in a single conformer in bulk solution. Using single
      molecule fluorescence methodology we have been able to detect these transitions.
      The sequence dependence, the influence of counterions and measured energetic
      barriers indicate that the conformer transition and branch migration processes
      share the unstacked, open structure as the common intermediate but have different
      rate-limiting steps. Relative rates indicate that multiple conformer transitions
      occur at each intermediate step of branch migration, allowing the junction to
      reach conformational equilibrium. This provides a mechanism whereby the sequence
      dependent conformational bias could determine the extent of genetic exchange upon
      junction resolution.

PMID- 12496934
TI  - Creation of a zymogen.
AB  - Cells produce proteases as inactive zymogens. Here, we demonstrate that this
      tactic can extend beyond proteases. By linking the N and C termini of
      ribonuclease A, we obstruct the active site with the amino acid sequence
      recognized by plasmepsin II, a highly specific protease from Plasmodium
      falciparum. We generate new N and C termini by circular permutation. In the
      presence of plasmepsin II, a ribonuclease zymogen gains approximately 10(3)-fold
      in catalytic activity and maintains high conformational stability. We conclude
      that zymogen creation provides a new and versatile strategy for the control of
      enzymatic activity, as well as the potential development of chemotherapeutic
      agents.

PMID- 12496935
TI  - Olanzapine and clozapine increase the GABAergic neuroactive steroid
      allopregnanolone in rodents.
AB  - The neuroactive steroid allopregnanolone is a potent gamma-aminobutyric acid type
      A (GABA(A)) receptor modulator with anxiolytic and anticonvulsant effects.
      Olanzapine and clozapine also have anxiolytic-like effects in behavioral models.
      We therefore postulated that olanzapine and clozapine would elevate
      allopregnanolone levels, but risperidone and haloperidol would have minimal
      effects. Male rats received intraperitoneal olanzapine (2.5-10.0 mg/kg),
      clozapine (5.0-20.0 mg/kg), risperidone (0.1-1.0 mg/kg), haloperidol (0.1-1.0
      mg/kg), or vehicle. Cerebral cortical allopregnanolone and peripheral
      progesterone and corticosterone levels were determined. Adrenalectomized animals
      were also examined. Both olanzapine and clozapine increased cerebral cortical
      allopregnanolone levels, but neither risperidone nor haloperidol had significant
      effects. Olanzapine and clozapine also increased serum progesterone and
      corticosterone levels. Adrenalectomy prevented olanzapine- and clozapine-induced
      elevations in allopregnanolone. Allopregnanolone induction may contribute to
      olanzapine and clozapine anxiolytic, antidepressant, and mood-stabilizing
      actions. Alterations in this neuroactive steroid may result in the modulation of
      GABAergic and dopaminergic neurotransmission, potentially contributing to
      antipsychotic efficacy.

PMID- 12496936
TI  - Neural activation profile elicited by cues associated with the anxiogenic drug
      yohimbine differs from that observed for reward-paired cues.
AB  - Cues associated with dangerous or rewarding outcomes can themselves elicit neural
      activation. Previous work in rats has shown that cues associated with morphine,
      cocaine, nicotine or palatable food can elicit enhanced expression of the
      immediate-early gene product Fos in discrete brain regions. Activation of the
      prefrontal cortex has been shown to be particularly prominent. Some studies have
      also shown prefrontal cortical activation following exposure to fear-inducing
      stimuli. To investigate the specificity of regional brain Fos activation, we
      treated rats with an anxiogenic drug, yohimbine (2 mg/kg, intraperitoneally
      (i.p.)), or water once per day for 10 consecutive days in a test environment
      distinct from their home cages. Yohimbine elicited a robust locomotor response
      that progressively sensitized over days. After a 4-day interval, rats were
      reintroduced to the paired environment, without drug treatment. Rats re-exposed
      to the environment where they had previously been treated with yohimbine showed
      conditioned increases in motor activity compared with controls. Fos expression
      was increased in several brain regions, including the basolateral amygdala, but
      was unchanged in prefrontal cortex, in contrast to what has been reported for
      rewarding drugs. These observations show a neural activation profile elicited by
      cues associated with the anxiogenic drug yohimbine and further support the
      hypothesis that prefrontal cortex has a specific role in reward expectancy.

PMID- 12496937
TI  - Action of three ectopeptidases on corticotropin-releasing factor: metabolism and
      functional aspects.
AB  - Using purified enzyme preparations, we investigated the actions of angiotensin
      converting enzyme, aminopeptidase N, and endopeptidase 24.11 on corticotropin
      releasing factor (CRF). The effects of inhibition of these enzymes on CRF action
      in rat anterior pituitary cultures were also determined. Finally, specific
      inhibitors were used to evaluate ectopeptidase action on the regional brain
      metabolism of CRF. K(m) values for CRF were 165, 90, and 42 microM for
      angiotensin-converting enzyme, aminopeptidase N, and endopeptidase 24.11,
      respectively. A CRF metabolite profile for each enzyme was determined. In
      pituitary cultures, inhibition of endopeptidase 24.11 and aminopeptidase N
      potentiated CRF-stimulated release of adrenocorticotropic hormone (ACTH). In rat
      pituitary and hypothalamus membrane preparations, specific inhibitor experiments
      indicated that CRF hydrolysis involved members of the neutral endopeptidase and
      aminopeptidase enzyme families. In cortex membranes, similar peptidase inhibition
      was without effect. These data support the hypothesis that ectopeptidases play a
      major role in CRF metabolism and biological function.

PMID- 12496938
TI  - Subchronic continuous phencyclidine administration potentiates amphetamine
      induced frontal cortex dopamine release.
AB  - Functional dopaminergic hyperactivity is a key feature of schizophrenia. Etiology
      of this dopaminergic hyperactivity, however, is unknown. We have recently
      demonstrated that subchronic phencyclidine (PCP) treatment in rodents induces
      striatal dopaminergic hyperactivity similar to that observed in schizophrenia.
      The present study investigates the ability of PCP to potentiate amphetamine
      induced dopamine release in prefrontal cortex (PFC) and nucleus accumbens (NAc)
      shell. Prefrontal dopaminergic hyperactivity is postulated to underlie cognitive
      dysfunction in schizophrenia. In contrast, the degree of NAc involvement is
      unknown and recent studies have suggested that PCP-induced hyperactivity in
      rodents may correlate with PFC, rather than NAc, dopamine levels. Rats were
      treated with 5-20 mg/kg/day PCP for 3-14 days by osmotic minipump. PFC and NAc
      dopamine release to amphetamine challenge (1 mg/kg) was monitored by in vivo
      microdialysis and HPLC-EC. Doses of 10 mg/kg/day and above produced serum PCP
      concentrations (50-150 ng/ml) most associated with PCP psychosis in humans. PCP
      treated rats showed significant, dose-dependent enhancement in amphetamine
      induced dopamine release in PFC but not NAc, along with significantly enhanced
      locomotor activity. Enhanced response was observed following 3-day, as well as 14
      day, treatment and resolved within 4 days of PCP treatment withdrawal. These
      findings support the concept that endogenous NMDA receptor dysfunction could
      account for the pattern of dopaminergic dysfunction observed in schizophrenia,
      and suggest that even short duration abuse of PCP-like agents may greatly
      potentiate behavioral effects of psychostimulants in drug abuse situations.
      Finally, these studies provide a model system in which to evaluate effects of
      potential psychotherapeutic agents.

PMID- 12496939
TI  - Group II metabotropic glutamate receptor modulation of DOI-induced c-fos mRNA and
      excitatory responses in the cerebral cortex.
AB  - Recent studies have demonstrated that the hallucinogen 1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane (DOI) enhances glutamatergic transmission in the
      prefrontal cortex. This increase can be suppressed by metabotropic glutamate2/3
      (mGlu2/3) receptor activation. In addition to enhancing glutamatergic
      transmission, DOI increases cortical c-fos expression. We tested if a reduction
      in glutamate release produced by mGlu2/3 receptor activation attenuates DOI
      induced c-fos expression in the cortex. Similar to previous studies, DOI produced
      a robust increase in c-fos mRNA throughout the cortex, including the prefrontal,
      frontoparietal, and somatosensory regions. Pretreatment with the mGlu2/3 agonist
      LY379268 attenuated the DOI-induced increase in the prefrontal cortex. This
      suppression was blocked by the mGlu2/3 antagonist LY341495. In contrast, the DOI
      induced increase in c-fos mRNA in the frontoparietal and somatosensory cortex was
      unaffected by the mGlu2/3 agents. These findings suggest that Group II
      metabotropic glutamate receptor agonists are capable of modulating postsynaptic
      function preferentially in the limbic cortex under conditions of enhanced
      glutamate release.

PMID- 12496940
TI  - Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF,
      Bcl-2 and Cu/Zn-SOD in rat hippocampus.
AB  - It has been proposed that antidepressants have neuroprotective effects on
      hippocampal neurons. To further test this hypothesis, brain-derived neurotrophic
      factor (BDNF), B cell lymphoma protein-2 (Bcl-2), and copper-zinc superoxide
      dismutase (Cu/Zn-SOD) were examined immunohistochemically in hippocampal neurons
      of Sprague-Dawley rats following daily treatment with 5 or 10 mg/kg of
      amitriptyline or venlafaxine for 21 days. At 5 mg/kg, both amitriptyline and
      venlafaxine increased the intensity of BDNF immunostaining in hippocampal
      pyramidal neurons, and the intensity of Bcl-2 immunostaining in hippocampal mossy
      fibers, but did not alter the Cu/Zn-SOD immunoreactivity. The high dose of
      venlafaxine, however, decreased the intensity of BDNF immunostaining in all
      subareas of the hippocampus and increased the intensity of Cu/Zn-SOD
      immunostaining in the dentate granular cell layer. The high dose of amitriptyline
      increased the intensity of Cu/Zn-SOD immunostaining, but did not affect the
      immunoreactivity of Bcl-2 or BDNF. These findings suggest that the chronic
      administration of amitriptyline or venlafaxine at 5 mg/kg, but not 10 mg/kg, may
      be neuroprotective to hippocampal neurons. These dose-related effects of
      antidepressant drugs on hippocampal neurons may have relevance to disparate
      findings in the field.

PMID- 12496941
TI  - Chronic exposure to cold stress alters electrophysiological properties of locus
      coeruleus neurons recorded in vitro.
AB  - Chronic stress exposure can alter central noradrenergic function. Previously, we
      reported that in chronically cold-exposed rats the release of norepinephrine and
      electrophysiological activation of locus coeruleus (LC) neurons is enhanced in
      response to multiple excitatory stimuli without alterations in basal activity. In
      the present studies, we used in vitro intracellular recording techniques to
      explore the effect of chronic cold exposure on the basal and evoked
      electrophysiological properties of LC neurons in horizontal slices of the rat
      brainstem. Consistent with our findings from in vivo experiments, chronic cold
      exposure did not affect basal firing rate. Furthermore, gross morphology of LC
      neurons and spike waveform characteristics were similar in slices from control
      and previously cold-exposed rats. However, excitability in response to
      intracellular current injection and input resistance were larger in slices from
      previously cold-exposed rats. In addition, the accommodation of spike firing in
      response to sustained current injection was smaller and the period of
      postactivation inhibition appeared to be less in LC neurons from cold-exposed
      rats. These data demonstrate that the stress-evoked sensitization of LC neurons
      observed in vivo is at least in part maintained in the slice preparation and
      suggest that alterations in electrophysiological properties of LC neurons
      contribute to the chronic stress-induced sensitization of central noradrenergic
      function observed in vivo. Furthermore, the present data suggest that an
      alteration in autoinhibitory control of LC activity is involved in the chronic
      stress-induced alterations. The enhanced functional capacity of LC neurons
      following cold exposure of rats may represent a unique model to study the
      mechanisms underlying the alterations in central noradrenergic function observed
      in humans afflicted with mood and anxiety disorders.

PMID- 12496942
TI  - Critical role for ventral tegmental glutamate in preference for a cocaine
      conditioned environment.
AB  - Cocaine administration induces glutamatergic activation within the mesolimbic
      accumbens system. This activation has been linked to the behavioral effects of
      cocaine and recently to the induction of long-term potentiation in dopamine
      neurons within the ventral tegmental area (VTA). We sought to determine if
      glutamate receptor activation is also crucial to the development of a conditioned
      place preference (CPP) to cocaine's rewarding effects. Two groups of rats were
      given intra-VTA injections of either vehicle or a combination of NMDA (N-methyl-D
      aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
      receptor antagonists (AP5 0.24 nmol plus CNQX 0.12 nmol per side) prior to each
      cocaine place-conditioning trial. Microinjections of the glutamate antagonists
      completely blocked the development of a cocaine CPP when given within, but not
      when given outside of, the VTA. These data indicate that glutamatergic activity
      in the VTA may be crucial for learning to associate environmental stimuli with
      cocaine exposure.

PMID- 12496943
TI  - Selective alleviation of compulsive lever-pressing in rats by D1, but not D2,
      blockade: possible implications for the involvement of D1 receptors in obsessive
      compulsive disorder.
AB  - Rats undergoing extinction of lever-pressing for food after the attenuation of an
      external feedback for this behavior exhibit excessive lever-pressing
      unaccompanied by an attempt to collect a reward. This behavior may be analogous
      to the excessive and unreasonable behavior seen in obsessive-compulsive disorder.
      In the present study, we tested the hypothesis that the compulsive behavior
      induced by signal attenuation is mediated via D(1) rather than D(2) receptors.
      Administration of 0.005, 0.01 and 0.03 mg/kg of the D(1) antagonist SCH 23390
      reduced the number of compulsive lever-presses without affecting the number of
      lever-presses followed by an attempt to collect a reward. In contrast,
      administration of 0.005, 0.01, 0.024, 0.036 and 0.05 of the D(2) antagonist
      haloperidol dose-dependently decreased both types of lever-presses. In addition,
      haloperidol at doses that decreased lever-pressing in the post-training signal
      attenuation procedure (0.036 and 0.05 mg/kg) had a similar effect in regular
      extinction, whereas an SCH 23390 dose that decreased compulsive lever-pressing in
      the post-training signal attenuation procedure (0.01 mg/kg) had no effect on
      regular extinction. On the basis of electrophysiological data on the response of
      dopamine neurons to the omission of an expected reward, these results were
      interpreted as suggesting that compulsive lever-pressing depends on a phasic
      decrease in the stimulation of D(1) receptors. The implications of these results
      for the pathophysiology and treatment of obsessive-compulsive disorder are
      discussed.

PMID- 12496944
TI  - Congenic D1A dopamine receptor mutants: ethologically based resolution of
      behavioural topography indicates genetic background as a determinant of knockout
      phenotype.
AB  - D(1A)-null mice were backcrossed over 14 generations into a C57BL/6 background to
      result in essential elimination (to <0.005%) of any contribution from the 129/Sv
      component of their initially mixed (129/SvxC57BL/6) background. Their phenotype
      was assessed using an ethologically based approach that resolves each individual
      topography of behaviour in the natural repertoire. Habituation of sniffing,
      locomotion, rearing seated, and rearing to wall in wild types over several hours
      was profoundly retarded in congenic D(1A) mutants; conversely, rearing free and
      sifting were essentially abolished. Resultant increases in individual
      topographies of behaviour were substantially greater in congenic D(1A) mutants
      than in those on a mixed background. This phenotype was little altered by the
      selective D(1)-like antagonist SCH 23390 and could not be blocked by the
      selective D(2)-like antagonist YM 09151-2. The selective D(1)-like agonist SK&F
      83959 could not further elevate those behaviours already heightened in congenic
      D(1A) mutants, while the induction of stereotyped sniffing and plodding
      locomotion by the selective D(2)-like agonist RU 24213 was disrupted. Genetic
      background appears to modulate critically the magnitude but not the general
      nature of the D(1A)-null phenotype, which may involve compensatory processes
      independent of other D(1)-like or D(2)-like receptors.

PMID- 12496945
TI  - 7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel
      environment.
AB  - The D3 dopamine receptor is expressed primarily in limbic brain areas, and
      appears to play an inhibitory role in rodent locomotor behavior. Evidence
      suggests a potential role for the D3 receptor in the pathology of
      neuropsychiatric disease. Progress in elucidating D3 receptor function has been
      hampered, however, by a lack of well-characterized, selective ligands and by
      conflicting information regarding the behavioral phenotype of D3 receptor
      knockout mice. Here, we describe studies evaluating the behavioral effects of (+/
      )-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) and PD 128907, two D3
      receptor agonists whose in vivo selectivity has been a topic of considerable
      controversy. We demonstrate that both compounds inhibit locomotion under novel
      environmental conditions in wild-type (WT) mice, but are without measurable
      behavioral effect under identical conditions in D3 receptor knockout mice.
      Additionally, we demonstrate that at low, D3 selective doses, these compounds are
      without behavioral effect in both WT and D3 receptor knockout mice that have
      acclimated to the testing environment. These findings suggest that D3 receptor
      stimulation inhibits novelty-stimulated locomotion, and establish conditions for
      the use of 7-OH-DPAT and PD 128907 as D3 receptor agonists in vivo. Potential
      implications of these observations are discussed.

PMID- 12496946
TI  - Dopamine D1 rather than D2 receptor agonists disrupt prepulse inhibition of
      startle in mice.
AB  - Although substantial literature describes the modulation of prepulse inhibition
      (PPI) by dopamine (DA) in rats, few reports address the effects of dopaminergic
      manipulations on PPI in mice. We characterized the effects of subtype-specific DA
      agonists in the PPI paradigm to further delineate the specific influences of each
      DA receptor subtype on sensorimotor gating in mice. The mixed D1/D2 agonist
      apomorphine and the preferential D1-family agonists SKF82958 and dihydrexidine
      significantly disrupted PPI, with differing or no effects on startle. In contrast
      to findings in rats, the D2/D3 agonist quinpirole reduced startle but had no
      effect on PPI. Pergolide, which has affinity for D2/D3 and D1-like receptors,
      reduced both startle and PPI, but only at the higher, nonspecific doses. In
      addition, the D1-family receptor antagonist SCH23390 blocked the PPI-disruptive
      effects of apomorphine on PPI, but the D2-family receptor antagonist raclopride
      failed to alter the disruptive effect of apomorphine. These studies reveal
      potential species differences in the DA receptor modulation of PPI between rats
      and mice, where D1-family receptors may play a more prominent and independent
      role in the modulation of PPI in mice than in rats. Nevertheless, due to the
      limited selectivity of DA receptor agonists, further studies using specific
      receptor knockout mice are warranted to clarify the respective roles of specific
      DA receptor subtypes in modulating PPI in mice.

PMID- 12496947
TI  - Flattening the corticosterone rhythm attenuates 5-HT1A autoreceptor function in
      the rat: relevance for depression.
AB  - Depression is associated with glucocorticoid abnormalities, in particular a
      flattening of the diurnal cortisol rhythm. Recent data suggest that an important
      factor in the aetiology of depression may be a deficit in the function and
      expression of 5-HT(1A) receptors, which has been reported in depressed patients.
      The present study assessed the possibility that this cortisol abnormality is
      causal in the 5-HT(1A) receptor deficits. First, a rat model of flattened
      glucocorticoid rhythm was developed. Controlled release corticosterone pellets
      implanted for 14 days flattened the corticosterone rhythm and maintained levels
      constant midway between the nadir and zenith levels observed in sham-operated
      rats. Secondly, using microdialysis to assess 5-HT release in the hippocampus,
      the inhibitory response to 8-OHDPAT was measured to determine the sensitivity of
      somatodendritic 5-HT(1A) autoreceptors. Corticosterone treatment was found to
      induce a significant attenuation in the response to 8-OHDPAT, indicating
      functional desensitization of somatodendritic 5-HT(1A) autoreceptors. There was
      no effect of corticosterone treatment on basal extracellular 5-HT levels. The
      data suggest that the glucocorticoid abnormalities associated with depression may
      impact on the functioning of 5-HT(1A) receptors in the brain. These findings
      suggest that resolution of cortisol abnormalities may be a valuable target for
      pharmacotherapy in the treatment of depression.

PMID- 12496948
TI  - Fluvoxamine reduces responsiveness of HPA axis in adult female BPD patients with
      a history of sustained childhood abuse.
AB  - The aim of the study is to test whether fluvoxamine affects the function of the
      hypothalamic pituitary adrenal (HPA) axis in female borderline (borderline
      personality disorder, BPD) patients with and without a history of sustained
      childhood abuse. Special attention is given to the presence of comorbid major
      depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The HPA axis
      of 30 female BPD patients with (n = 17) and without (n = 13) a history of
      sustained childhood abuse was challenged with a combined dexamethasone and
      corticotropin releasing hormone test (DEX/CRH test) before and after 6 (n = 14)
      and 12 (n = 16) weeks of fluvoxamine treatment (150 mg/day). Both 6- and 12-week
      fluvoxamine treatments were associated with a significant and robust reduction of
      the adrenocorticotrophic hormone (ACTH) and cortisol response to the DEX/CRH
      test. The magnitude of the reduction was dependent on the presence of sustained
      childhood abuse, but not on the presence of comorbid MDD or PTSD: patients with a
      history of sustained childhood abuse showed the strongest reduction in ACTH and
      cortisol. In conclusion, Fluvoxamine treatment reduces the hyperresponsiveness of
      the HPA axis in BPD patients with a history of sustained childhood abuse. This
      effect is likely to be obtained in the first 6 weeks of treatment.

PMID- 12496949
TI  - Central serotonergic effects of m-chlorophenylpiperazine (mCPP) among normal
      control adolescents.
AB  - Central serotonin function was studied among 21 adolescents (12 males, 9
      females), mean age 14.4+/-1.5 years. A placebo-controlled design was used to
      measure three neuroendocrine hormones (prolactin, cortisol and growth hormone)
      following a challenge with the central serotonergic agonist m
      chlorophenylpiperazine (mCPP). Infusion of mCPP resulted in augmented prolactin,
      cortisol and growth hormone release. Gender effects were significant for
      prolactin, cortisol and growth hormone. Females had higher baseline prolactin
      without significant interactions with infusion or time, cortisol levels were
      higher in males than in females at all time points without significant
      interactions with infusion or time, and the augmented growth hormone response to
      mCPP was limited to males. Systolic and diastolic blood pressure, heart rate and
      temperature were all mildly elevated following mCPP infusion. Side effects to
      mCPP infusion were mild and lasted approximately 20 min. We conclude that mCPP is
      useful in the study of serotonergic neuroendocrine hormones in adolescents, is
      well tolerated, and the levels of prolactin, cortisol and growth hormone are
      influenced by gender.

PMID- 12496950
TI  - Anxious-retarded depression: relation with plasma vasopressin and cortisol.
AB  - Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is related to
      melancholic or endogenous depression; however, the strength of this relationship
      depends on the definition of the specific depression subcategory. A two
      dimensionally defined subcategory, anxious-retarded depression, is related to
      melancholic depression. Since arginine vasopressin (AVP) activates the HPA axis,
      and both major depression and the melancholic subcategory are associated with
      elevated plasma AVP levels, we investigated whether the plasma AVP level is also
      elevated in anxious-retarded depression, melancholic depression and anxious
      retarded melancholic depression, and whether plasma AVP and cortisol levels are
      correlated in these subcategories. A total of 66 patients with major depression
      not using oral contraception were investigated. Patients with anxious-retarded
      depression had a highly significant AVP-cortisol correlation, while no such
      correlation was found in patients with nonanxious-retarded depression. Log
      transformed mean plasma AVP values were higher in patients with anxious-retarded
      depression than in patients with nonanxious-retarded depression. Patients with
      anxious-retarded melancholic depression also had a significantly elevated level
      of plasma AVP and a highly significant correlation between plasma AVP and
      cortisol levels. The correlation was low in patients with melancholic depression.
      Anxious-retarded depression may be a useful refinement of the melancholic
      subcategory with regard to dysregulation of the HPA axis and plasma AVP release.

PMID- 12496951
TI  - Acute SSRI administration affects the processing of social cues in healthy
      volunteers.
AB  - Enhancement of serotonin neurotransmission plays an important role in the
      antidepressant response to agents presently available to treat depression. This
      response forms the major evidence for the role of serotonin in affective and
      social behaviour in humans. The present study investigated the effects of acute
      administration of the selective serotonin reuptake inhibitor (SSR1), citalopram
      (10 mg, i.v.) upon a measure of emotional processing in healthy female
      volunteers. Subjects completed a facial expression recognition task following
      infusion of citalopram or saline (between-subjects design, double-blind). Facial
      expressions associated with five basic emotions--happiness, sadness, fearfulness,
      anger and disgust--were displayed. Each face had been 'morphed' between neutral
      (0%) and each emotional standard (100%) in 10% steps, leading to a range of
      emotional intensities. Mood and subjective experience were also monitored
      throughout the testing session. Volunteers receiving citalopram detected a higher
      number of facial expressions of fear and happiness, with reduced response times,
      relative to those given the placebo. By contrast, changes in the recognition of
      other basic emotions were not observed following citalopram. Notable differences
      in mood were also not apparent in these volunteers. These results suggest that
      acute administration of antidepressant drugs may affect neural processes involved
      in the processing of social information. This effect may represent an early acute
      effect of SSRIs on social and emotional processing that is relevant to their
      therapeutic actions.

PMID- 12496952
TI  - Tryptophan depletion alters the decision-making of healthy volunteers through
      altered processing of reward cues.
AB  - While accumulating evidence suggests that effective real-life decision-making
      depends upon the functioning of the orbitofrontal cortex, much less is known
      about the involvement of the monoamine neurotransmitter systems and, in
      particular, serotonin. In the present study, we explored the impact of depleting
      the serotonin precursor, tryptophan, on human decision-making. Eighteen healthy
      volunteers consumed an amino-acid drink containing tryptophan and 18 healthy
      volunteers consumed an amino-acid drink without tryptophan, before choosing
      between simultaneously presented gambles, differing in the magnitude of expected
      gains (ie reward), the magnitude of expected losses (ie punishment), and the
      probabilities with which these outcomes were delivered. Volunteers also chose
      between gambles probing identified non-nomative biases in human decision-making,
      namely, risk-aversion when choosing between gains and risk-seeking when choosing
      between losses. Tryptophan-depleted volunteers showed reduced discrimination
      between magnitudes of expected gains associated with different choices. There was
      little evidence that tryptophan depletion was associated with altered
      discrimination between the magnitudes of expected losses, or altered
      discrimination between the relative probabilities with which these positive or
      negative outcomes were delivered. Risk-averse and risk-seeking biases were also
      unchanged. These results suggest that serotonin mediates decision-making in
      healthy volunteers by modulating the processing of reward cues, perhaps
      represented within the orbitofrontal cortex. It is possible that such a change in
      the cognition mediating human choice is one mechanism associated with the onset
      and maintenance of anhedonia and lowered mood in psychiatric illness.

PMID- 12496953
TI  - Substance abuse disorder and major depression are associated with the human 5
      HT1B receptor gene (HTR1B) G861C polymorphism.
AB  - The 5-HT(1B) receptor has been implicated in several psychopathologies, including
      pathological aggression, alcoholism and suicide. To test these and related
      potential genetic relationships in a single population, the human 5-HT(1B)
      receptor (h5-HTR(1B)) genotype for the G861C polymorphism was determined in 394
      psychiatric patients and 96 healthy volunteers. Structured clinical interviews
      generated DSM III-R diagnoses. No significant association of the genotype or
      allele frequencies of the h5-HTR(1B) G861C locus was observed with diagnoses of
      alcoholism, bipolar disorder, schizophrenia or a history of a suicide attempt.
      Exploratory analyses indicated an association of the genotype and allele
      frequencies of the h5-HTR(1B) G861C locus with a history of substance abuse
      disorder (chi(2) = 9.51, df = 2, p = 0.009; chi(2) = 7.31, df = 1, p = 0.007,
      respectively) and with a diagnosis of a major depressive episode (chi(2) = 6.83,
      df = 2, p = 0.033; chi(2) = 5.81, df = 1, p = 0.016, respectively). Significant
      gene dose effects on the risk for substance abuse disorder and a major depressive
      episode were observed with the 861C allele (Armitage linearity tendency test:
      chi(2) = 7.20, df = 1, p = 0.008; chi(2) = 6.80, df = 1, p = 0.009,
      respectively). Substance abuse disorder and major depression appear to be
      associated with the h5-HTR(1B) G861C locus in the patient population, but other
      psychopathologies such as bipolar disorder, schizophrenia, alcoholism, and
      suicide attempts were not found to be associated with this polymorphism. This
      preliminary result will need replication, given the limitations of association
      studies.

PMID- 12496954
TI  - Effects of the 5-HT2A agonist psilocybin on mismatch negativity generation and AX
      continuous performance task: implications for the neuropharmacology of cognitive
      deficits in schizophrenia.
AB  - Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine
      was shown to disrupt generation of the auditory event-related potential (ERP)
      mismatch negativity (MMN) and the performance of an 'AX'-type continuous
      performance test (AX-CPT)--measures of auditory and visual context-dependent
      information processing--in a similar manner as observed in schizophrenia. This
      placebo-controlled study investigated effects of the 5-HT(2A) receptor agonist
      psilocybin on the same measures in 18 healthy volunteers. Psilocybin
      administration induced significant performance deficits in the AX-CPT, but failed
      to reduce MMN generation significantly. These results indirectly support evidence
      that deficient MMN generation in schizophrenia may be a relatively distinct
      manifestation of deficient NMDAR functioning. In contrast, secondary
      pharmacological effects shared by NMDAR antagonists and the 5-HT(2A) agonist (ie
      disruption of glutamatergic neurotransmission) may be the mechanism underlying
      impairments in AX-CPT performance observed during both psilocybin and ketamine
      administration. Comparable deficits in schizophrenia may result from independent
      dysfunctions of 5-HT(2A) and NMDAR-related neurotransmission.

PMID- 12496955
TI  - Effect of divalproex combined with olanzapine or risperidone in patients with an
      acute exacerbation of schizophrenia.
AB  - This double-blind, randomized, multicenter study investigated the use of
      divalproex with an antipsychotic agent in patients hospitalized for acute
      exacerbation of schizophrenia. Patients (n = 249) who met DSM-IV criteria for
      schizophrenia were randomly assigned to receive olanzapine monotherapy,
      risperidone monotherapy, divalproex plus olanzapine, or divalproex plus
      risperidone for 28 days. Divalproex was initiated at 15 mg/kg/day and titrated
      over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone,
      were, respectively, initiated at 5 and 2 mg/day and were titrated over the first
      6 days to respective target fixed daily dosages of 15 and 6 mg/day. Improvements
      from baseline were observed at all evaluation points throughout the 28-day
      treatment period in the two combination therapy and the two antipsychotic
      monotherapy groups, with statistically significant treatment differences favoring
      combination therapy as soon as day 3 for Positive and Negative Syndrome Scale
      (PANSS) total score, derived Brief Psychiatric Rating Scale (BPRSd) total score,
      as well as PANSS and BPRSd subscales. These findings were confirmed in post hoc
      repeated-measures analyses of variance in which treatment differences favoring
      combination therapy were observed for PANSS total (p = 0.020) and PANSS positive
      scale scores (p = 0.002). Both combination therapy and antipsychotic monotherapy
      were well tolerated. Treatment with divalproex in combination with an atypical
      antipsychotic agent resulted in earlier improvements in a range of psychotic
      symptoms among acutely hospitalized patients with schizophrenia. Further
      evaluation is warranted to confirm these findings.

PMID- 12496956
TI  - Oxytocin infusion reduces repetitive behaviors in adults with autistic and
      Asperger's disorders.
AB  - Autism is a neurodevelopmental disorder characterized by dysfunction in three
      core behavioral domains: repetitive behaviors, social deficits, and language
      abnormalities. There is evidence that abnormalities exist in peptide systems,
      particularly the oxytocin system, in autism spectrum patients. Furthermore,
      oxytocin and the closely related peptide vasopressin are known to play a role in
      social and repetitive behaviors. This study examined the impact of oxytocin on
      repetitive behaviors in 15 adults with autism or Asperger's disorder via
      randomized double-blind oxytocin and placebo challenges. The primary outcome
      measure was an instrument rating six repetitive behaviors: need to know,
      repeating, ordering, need to tell/ask, self-injury, and touching. Patients with
      autism spectrum disorders showed a significant reduction in repetitive behaviors
      following oxytocin infusion in comparison to placebo infusion. Repetitive
      behavior in autism spectrum disorders may be related to abnormalities in the
      oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.

PMID- 12496958
TI  - Melusin, a muscle-specific integrin beta1-interacting protein, is required to
      prevent cardiac failure in response to chronic pressure overload.
AB  - Cardiac hypertrophy is an adaptive response to a variety of mechanical and
      hormonal stimuli, and represents an early event in the clinical course leading to
      heart failure. By gene inactivation, we demonstrate here a crucial role of
      melusin, a muscle-specific protein that interacts with the integrin beta1
      cytoplasmic domain, in the hypertrophic response to mechanical overload. Melusin
      null mice showed normal cardiac structure and function in physiological
      conditions, but when subjected to pressure overload--a condition that induces a
      hypertrophic response in wild-type controls--they developed an abnormal cardiac
      remodeling that evolved into dilated cardiomyopathy and contractile dysfunction.
      In contrast, the hypertrophic response was identical in wild-type and melusin
      null mice after chronic administration of angiotensin II or phenylephrine at
      doses that do not increase blood pressure--that is, in the absence of cardiac
      biomechanical stress. Analysis of intracellular signaling events induced by
      pressure overload indicated that phosphorylation of glycogen synthase kinase
      3beta (GSK-3beta) was specifically blunted in melusin-null hearts. Thus, melusin
      prevents cardiac dilation during chronic pressure overload by specifically
      sensing mechanical stress.

PMID- 12496959
TI  - Therapeutic dendritic-cell vaccine for simian AIDS.
AB  - An effective immune response against human immunodeficiency virus or simian
      immunodeficiency virus (SIV) is critical in achieving control of viral
      replication. Here, we show in SIV-infected rhesus monkeys that an effective and
      durable SIV-specific cellular and humoral immunity is elicited by a vaccination
      with chemically inactivated SIV-pulsed dendritic cells. After three immunizations
      made at two-week intervals, the animals exhibited a 50-fold decrease of SIV DNA
      and a 1,000-fold decrease of SIV RNA in peripheral blood. Such reduced viral load
      levels were maintained over the remaining 34 weeks of the study. Molecular and
      cellular analyses of axillary and inguinal node lymphocytes of vaccinated monkeys
      revealed a correlation between decreased SIV DNA and RNA levels and increased SIV
      specific T-cell responses. Neutralizing antibody responses were augmented and
      remained elevated. Inactivated whole virus-pulsed dendritic cell vaccines are
      promising means to control diseases caused by immuno- deficiency viruses.

PMID- 12496960
TI  - Human and porcine early kidney precursors as a new source for transplantation.
AB  - Kidney transplantation has been one of the major medical advances of the past 30
      years. However, tissue availability remains a major obstacle. This can
      potentially be overcome by the use of undifferentiated or partially developed
      kidney precursor cells derived from early embryos and fetal tissue. Here,
      transplantation in mice reveals the earliest gestational time point at which
      kidney precursor cells, of both human and pig origin, differentiate into
      functional nephrons and not into other, non-renal professional cell types.
      Moreover, successful organogenesis is achieved when using the early kidney
      precursors, but not later-gestation kidneys. The formed, miniature kidneys are
      functional as evidenced by the dilute urine they produce. In addition, decreased
      immunogenicity of the transplants of early human and pig kidney precursors
      compared with adult kidney transplants is demonstrated in vivo. Our data pinpoint
      a window of human and pig kidney organogenesis that may be optimal for
      transplantation in humans.

PMID- 12496961
TI  - Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate
      antiviral pathways.
AB  - Cancer vaccines targeting 'self' antigens that are expressed at consistently high
      levels by tumor cells are potentially useful in immunotherapy, but immunological
      tolerance may block their function. Here, we describe a novel, naked DNA vaccine
      encoding an alphavirus replicon (self-replicating mRNA) and the self/tumor
      antigen tyrosinase-related protein-1. Unlike conventional DNA vaccines, this
      vaccine can break tolerance and provide immunity to melanoma. The vaccine
      mediates production of double-stranded RNA, as evidenced by the
      autophosphorylation of dsRNA-dependent protein kinase R (PKR). Double-stranded
      RNA is critical to vaccine function because both the immunogenicity and the anti
      tumor activity of the vaccine are blocked in mice deficient for the RNase L
      enzyme, a key component of the 2',5'-linked oligoadenylate synthetase antiviral
      pathway involved in double-stranded RNA recognition. This study shows for the
      first time that alphaviral replicon-encoding DNA vaccines activate innate immune
      pathways known to drive antiviral immune responses, and points the way to
      strategies for improving the efficacy of immunization with naked DNA.

PMID- 12496962
TI  - Ezh2 controls B cell development through histone H3 methylation and Igh
      rearrangement.
AB  - Polycomb group protein Ezh2 is an essential epigenetic regulator of embryonic
      development in mice, but its role in the adult organism is unknown. High
      expression of Ezh2 in developing murine lymphocytes suggests Ezh2 involvement in
      lymphopoiesis. Using Cre-mediated conditional mutagenesis, we demonstrated a
      critical role for Ezh2 in early B cell development and rearrangement of the
      immunoglobulin heavy chain gene (Igh). We also revealed Ezh2 as a key regulator
      of histone H3 methylation in early B cell progenitors. Our data suggest Ezh2
      dependent histone H3 methylation as a novel regulatory mechanism controlling Igh
      rearrangement during early murine B cell development.

PMID- 12496963
TI  - CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR
      signaling.
AB  - The transmembrane phosphatase CD45 regulates both Lck activity and T cell
      receptor (TCR) signaling. Here we have tested whether the large ectodomain of
      CD45 has a role in this regulation. A CD45 chimera containing the large
      ectodomain of CD43 efficiently rescues TCR signaling in CD45-null T cells,
      whereas CD45 chimeras containing small ectodomains from other phosphatases do
      not. Both basal Lck activity in unstimulated cells and the TCR-induced increase
      in tyrosine phosphorylation of the TCR zeta-chain and in Lck activity depend on
      the expression of CD45 with a large ectodomain. Unlike CD45 chimeras containing
      small ectodomains, both the CD45 chimera with a large ectodomain and wild-type
      CD45 itself are partially localized to glycosphingolipid-enriched membranes
      (GEMs). Taken together, these data show that the large CD45 ectodomain is
      required for optimal TCR signaling.

PMID- 12496964
TI  - Functional interactions between dendritic cells and NK cells during viral
      infection.
AB  - Ly49H(+)NK1.1(+) natural killer (NK) cells are essential for the control of
      murine cytomegalovirus (MCMV) during the acute stage of infection. This cell
      subset expands at the later stages of infection in an MCMV-specific fashion. Here
      we demonstrate a critical interaction between Ly49H(+) NK cells and CD8alpha(+)
      dendritic cells (DCs) whereby the presence of Ly49H(+) NK cells results in
      maintenance of CD8alpha(+) DCs in the spleen during acute MCMV infection.
      Reciprocally, CD8alpha(+) DCs are essential for the expansion of Ly49H(+) NK
      cells by a mechanism involving interleukin 18 (IL-18) and IL-12. This study
      provides evidence for a functional interrelationship between DCs and NK cells
      during viral infection and defines some of the critical cytokines.

PMID- 12496965
TI  - Haves and have nots.

PMID- 12496966
TI  - PI3K comes of age.

PMID- 12496967
TI  - Darwinism and immunology: from Metchnikoff to Burnet.

PMID- 12496968
TI  - Yin outwits Yang at the IgE locus.

PMID- 12496969
TI  - Novel interferons.

PMID- 12496970
TI  - Regulatory T cells: mediating compromises between host and parasite.

PMID- 12496971
TI  - T cells versus HIV-1: fighting exhaustion as well as escape.

PMID- 12496972
TI  - Checks and balances on developing B cells.

PMID- 12496974
TI  - The dual-function CD150 receptor subfamily: the viral attraction.
AB  - The CD150 subfamily within the CD2 family is a growing group of dual-function
      receptors that have within their cytoplasmic tails a characteristic signaling
      motif. The ITSM (immunoreceptor tyrosine-based switch motif) enables these
      receptors to bind to and be regulated by small SH2 domain adaptor proteins,
      including SH2D1A (SH2-containing adaptor protein SH2 domain protein 1A) and EAT-2
      (EWS-activated transcript 2). A major signaling pathway through the prototypic
      receptor in this subfamily, CD150, leads to the activation of interferon-gamma, a
      key cytokine for viral immunity. As a result, many viruses have designed
      strategies to usurp or alter CD150 functions. Measles virus uses CD150 as a
      receptor and Molluscum contagiosum virus encodes proteins that are homologous to
      CD150. Thus, viruses use CD150 subfamily receptors to create a favorable
      environment to elude detection and destruction. Understanding the CD150 subfamily
      may lead to new strategies for vaccine development and antiviral therapies.

PMID- 12496976
TI  - What's hot in the prostate?

PMID- 12496977
TI  - Management of prostatitis.
AB  - Prostatitis is a common clinical entity with a prevalence rate of 5-9% and
      accounts for over 2 million hospital visits annually in the USA. It is
      traditionally classified into acute bacterial, chronic bacterial, abacterial
      prostatitis and prostatodynia. The recent consensus conference of the US National
      Institute of Diabetes and Digestive and Kidney Diseases in 2000 resulted in
      renewed interest in the prevalence, etiology, pathogenesis and treatment of the
      prostatitis syndromes. In this review, we present the contemporary knowledge and
      experience regarding the etiology, classification, evaluation and treatment of
      this condition including the role of transurethral microwave hyperthermia and
      transurethral needle ablation.

PMID- 12496978
TI  - Distal urethral web: a risk factor in prostatitis.
AB  - This study aims to identify a risk factor in the form of a distal urethral web in
      chronic prostatitis, resection of which should lead to significant symptom
      reduction. The distal urethral web has been identified as a risk factor in
      chronic prostatitis, surgical resection of which resulted in reduction of
      symptoms as measured by the prostatitis specific symptom indexes. A risk factor
      in chronic prostatitis has been identified as a reflux-causing distal urethral
      web, surgical resection of which resulted in significant symptom severity
      reduction and a smaller decline in the frequency of symptoms. Overall, this study
      shows that the distal urethral web is a risk factor for chronic prostatitis and
      chronic pelvic pain syndrome, and that its resection resulted in significant
      symptom severity reduction with a lesser decline in the frequency of symptoms.
      This would indicate that the patients rated surgery as having an overwhelming
      edge when it came to reducing the severity of symptoms, but not so overwhelming
      an edge as far as the frequency of symptoms was concerned. This is probably
      reflective of the patients' choice for a combination of surgery and conventional
      treatments rather than one or the other alone, and/or other risk factors as yet
      undiscovered. Like other treatments in the past, this may not be the complete
      answer to chronic pelvic pain syndrome (CPPS).

PMID- 12496979
TI  - Transurethral prostatic tissue ablation via a single needle delivery system:
      initial experience with radio-frequency energy and ethanol.
AB  - We report an initial clinical experience to evaluate the safety and efficacy of
      outpatient prostatic ablation for the treatment of symptomatic benign prostatic
      hyperplasia (BPH) using local anesthesia (OPAL) with radio-frequency energy and
      intraprostatic absolute ethanol injection (EI). Twenty-three patients were
      treated with OPAL and five patients were treated with EI. Pre-operative data for
      all patients included international prostate symptom score (IPSS), quality of
      life score (QL), maximum flow rate (Q(max)), and post void residual
      determination. Prostate specific antigen (PSA) and transrectal ultrasound
      prostate volume determination were also done for EI patients. Needle deployment
      into the prostate was carried out at the 2, 4, 8 and 10 o'clock positions for
      lateral lobe hyperplasia and the 6 o'clock position for middle lobe hyperplasia.
      IPSS, QL, Q(max) and post void residual data were collected at 1, 3, 6 and 12
      months post procedure. Both procedures resulted in statistically significant
      reductions of IPSS and QL. Trends towards improvement were seen both for Q(max)
      and post void residual, with Q(max) significantly improved after OPAL. Among EI
      patients, the prostate volume was reduced at 6 months post treatment to 37.2+/
      17.9 g from 53.0+/-19.0 g (P=0.03) preoperatively. OPAL was safe but suffered
      from a high re-treatment rate. EI demonstrated encouraging results with regards
      to safety, symptom improvement and prostate volume reduction.

PMID- 12496980
TI  - Association between the GCG polymorphism of the selenium dependent GPX1 gene and
      the risk of young onset prostate cancer.
AB  - Epidemiological studies have suggested an association between low selenium levels
      and the development of prostate cancer. Human cellular glutathione peroxidase I
      (hGPX1) is a selenium-dependent enzyme that protects against oxidative damage and
      its peroxidase activity is a plausible mechanism for cancer prevention by
      selenium. The GPX1 gene has a GCG repeat polymorphism in exon 1, coding for a
      polyalanine tract of five to seven alanine residues. To test if the GPX1 GCG
      repeat polymorphism associates with the risk of young-onset prostate cancer we
      conducted a case-control study. The GPX1Ala genotypes were determined for 267
      prostate cancer cases and 260 control individuals using polymerase chain reaction
      (PCR) amplification with fluorescently labelled primers and an ABI 377 automated
      genotyper. Associations between specific genotypes and the risk of prostate
      cancer were examined by logistic regression. We found no significant association
      between the GPX1 genotypes and prostate cancer. There was however an increased
      frequency of the GPX1Ala6/Ala6 genotype in the prostate cancer cases compared to
      controls (OR: 1.67; 95% CI: 0.97-2.87). The result of this study suggests that
      the GPX1 genotype is unlikely to be associated with the risk of developing
      prostate cancer.

PMID- 12496981
TI  - Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomy
      status, age at vasectomy, and time since vasectomy.
AB  - The aim of this study was to conduct a quantitative review of prostate cancer
      studies to pool relative risk (RR) estimates on the association between prostate
      cancer and vasectomy, in an attempt to determine whether there is an association,
      and if so, its magnitude. Random-effects models were examined along with a linear
      model for time since vasectomy. The pooled RR estimate was 1.37 (95% CI=1.15
      1.62) based on five cohort studies and 17 case-control studies. The RR estimate
      varied by study design with the lowest risk for population-based case-control
      studies. No difference was seen in risk by age at vasectomy. A linear trend based
      on the 16 studies reporting time since vasectomy suggested an 10% increase for
      each additional 10 y or a RR of 1.32 (95% CI=1.17-1.50) for 30 y since vasectomy.
      When null effects were assumed for the six studies not reporting information, the
      linear RR for the 22 studies was 1.07 (1.03-1.11) and 1.23 (1.11-1.37) for 10 and
      30 y since vasectomy, respectively. These results suggest that men with a prior
      vasectomy may be at an increased risk of prostate cancer, however, the increase
      may not be causal since potential bias cannot be discounted. The overall
      association was small and therefore could be explained by bias. The latency
      effect shown here for time since vasectomy should be examined further.

PMID- 12496982
TI  - Investigating the distribution of prostate cancer using three-dimensional
      computer simulation.
AB  - The objective of this work was to investigate the distribution of prostate cancer
      using three-dimensional (3-D) computer simulation. Two hundred and eighty-one 3-D
      computer prostate models were constructed from radical prostatectomy specimens.
      An algorithm was developed which divided each model into 24 symmetrical regions,
      and it then detected the presence of tumor within an individual region. The
      distribution rate of prostate cancer was assessed within each region of all 281
      prostate models, and the difference between the rates was statistically analyzed
      using Mantel-Haenszel methodology. There was a statistically significant higher
      distribution rate of cancer in the posterior half (57.2%) compared to the
      anterior half ( 40.5%; P=0.001). The base regions (36.8%) had a statistically
      significant lower distribution rate than either the mid regions (56.3%; P=0.001)
      or the apical regions (53.5%; P=0.001). The mid regions did have a statistically
      significant higher distribution rate compared to the apical regions (P=0.032).
      There was no statistically significant difference between the distribution rate
      on the left half (48.5%) compared to that on the right half (49.2%; P=0.494). The
      spatial distribution of prostate cancer can be analyzed using 3-D computer
      prostate models. The results illustrate that prostate cancer is least commonly
      located in the anterior half and base regions of the prostate. Through an
      analysis of the spatial distribution of prostate cancer, we believe that new
      optimal biopsy strategies and techniques can be developed.

PMID- 12496983
TI  - Pain perception during transrectal ultrasound guided prostate needle biopsy: an
      objective analysis of local anesthesia use.
AB  - We assessed the effect of periprostatic nerve blockade during transrectal
      ultrasound of the prostate prior to obtaining systematic needle biopsies and the
      discomfort associated with this procedure. A prospective randomized study was
      performed on 100 men requiring systematic needle biopsy of the prostate. Patients
      were assigned to two groups: Group 1 received no local anesthesia and Group 2
      received a periprostatic injection of 5 ml 1% lidocaine solution (2.5 ml
      bilaterally) prior to undergoing biopsy of the prostate. The patients were asked
      to respond to a pre- and post-procedural questionnaire which consisted of four
      questions designed to evaluate pain perception and pain experienced,
      respectively, during the entire procedure. Mean pain scores for Group 1 responses
      vs Group 2 responses were not statistically different for any of the pre
      procedural questions. Post-procedural pain scores were significantly lower in
      Group 2 vs Group 1 (control) for questions 1 and 3: question 1 (2.6+/-1.8 vs
      3.8+/-1.8, P<0.05), question 2 (3.0+/-1.9 vs 3.7+/-2.1, P=0.14). Question 3
      (2.8+/-2.0 vs 4.3+/-1.9, P<0.05), and question 4 (1.6+/-2.4 vs 2.1+/-2.6,
      P=0.38). During the study, no patient from Group 2 experienced any adverse
      reaction from the injection. Our data suggest that periprostatic nerve blockade
      during transrectal ultrasound of the prostate results in less patient discomfort.

PMID- 12496984
TI  - Complete embedding and close step-sectioning of radical prostatectomy specimens
      both increase detection of extra-prostatic extension, and correlate with
      increased disease-free survival by stage of prostate cancer patients.
AB  - The objectives of this work were to evaluate the efficacy of controlled close
      step-sectioned and whole-mounted radical prostatectomy specimen processing in
      prediction of clinical outcome as compared to the traditional processing
      techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were
      whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals.
      A group of 682 radical prostatectomy specimens were partially sampled as control.
      The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months,
      pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival
      based on biochemical or clinical recurrence and secondary intervention were
      computed using a Kaplan-Meier analysis. There were no significant differences in
      age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the
      two groups (P<0.05). Compared with the non-close step-sectioned group, the close
      step-sectioned group showed higher detection rates of extra-prostatic extension
      (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs
      35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y
      disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01)
      cases, over the non-uniform group. The close step-sectioned group showed
      significantly higher disease-free survival for cases with seminal vesicle
      invasion (P=0.046). No significant difference in disease-free survival was found
      for the positive margin group (P=0.39) between the close step-sectioned and non
      uniform groups. The close step-sectioned technique correlates with increased
      disease-free survival rates for organ and specimen confined cases, possibly due
      to higher detection rates of extra-prostatic extension and seminal vesicle
      invasion. Close step-sectioning provides better assurance of organ-confined
      disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.

PMID- 12496985
TI  - Multimodality radiotherapy and androgen ablation in the treatment of clinically
      localized prostate cancer: early results in high risk patients.
AB  - In patients presenting with clinically localized prostate cancer, the risk of
      biochemical failure increases significantly with higher Gleason scores, prostate
      specific antigen (PSA) levels, and clinical stages. Current surgical and
      radiotherapeutic approaches appear to offer limited success in patients with
      highly adverse prognostic factors. In an attempt to improve on these outcomes, we
      have combined external beam radiotherapy (EBRT) with a brachytherapy (BT) boost
      and neo adjuvant and adjuvant androgen ablation in a population at significant
      risk of biochemical failure. Here we present early biochemical progression data
      for this approach. From October 1997 to July 1999, 72 men with a serum PSA >or=10
      ng/ml or Gleason score >or=7 or clinical stage >or=T2c (AJC/UICC 1992) underwent
      EBRT followed by palladium-103 BT. All patients underwent 8 months of combined
      androgen ablation with leuprolide and an oral antiandrogen beginning 3 months
      prior to initiation of EBRT. Patients were followed by PSA and digital rectal
      examination (DRE) at 3-month intervals and a chart review on all patients was
      carried out during July 2001. To allow comparisons to contemporary literature,
      Kaplan-Meier survival curves were generated utilizing three alternate definitions
      of biochemical recurrence: PSA >0.2 ng/ml, PSA >1.0 ng/ml, and the American
      Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition of
      three consecutive rising PSAs. Our results indicate that when PSA >0.2 ng/ml was
      used to define biochemical progression, 88% (95% CI 80-97) of patients remained
      free of disease at 24 months. When PSA >1.0 ng/ml was used, 97% (CI 92-100) of
      patients remained disease free at 24 months. ASTRO criteria yielded 90% (CI 82
      98) recurrence-free survival at 24 months. In conclusion, this very early report
      indicates that in patients who are at increased risk of biochemical failure, EBRT
      with a BT boost in conjunction with short-term androgen ablation offers
      potentially superior biochemical disease-free survival to contemporary
      alternative approaches in the literature. Clearly, longer follow-up is required
      to confirm the durability of this approach.

PMID- 12496986
TI  - Can single dose preoperative intrathecal morphine sulfate provide cost-effective
      postoperative analgesia and patient satisfaction during radical prostatectomy in
      the current era of cost containment?
AB  - We retrospectively analyzed the analgesic efficacy and surgical outcomes of a
      single preoperative intrathecal long-acting morphine sulfate injection (0.25-0.5
      mg) and postoperative intravenous (i.v.) ketorolac in 62 patients who underwent
      radical retropubic prostatectomy (RRP). Total postoperative analgesic requirement
      was documented along with assessment of length of hospital stay, pain control and
      time for resumption of normal activity. Postoperatively, 45% of patients required
      only nonsteroidal agents (ketorolac), whereas 55% needed a mean of 13.3 mg of
      supplemental i.v. morphine sulfate. Mean hospital stay was 2.3+/-0.3 days. Eighty
      two per cent of patients felt the length of hospital stay adequate. Ninety-seven
      per cent of patients were satisfied with anesthesia selected and 95% of patients
      considered pain control on postoperative days 1 and 2 as effective. All patients
      resumed to full physical activity by 5.3+/-0.4 weeks after surgery. We conclude
      that a single preoperative injection of intrathecal morphine sulfate combined
      with i.v. ketorolac postoperatively results in effective analgesia, diminished
      supplemental narcotic requirement and high patient satisfaction during radical
      retropubic prostatectomy.

PMID- 12496987
TI  - Ibandronate in the treatment of prostate cancer associated painful osseous
      metastases.
AB  - The aim of our study was to assess the clinical efficacy and toxicity of
      ibandronate in the management of symptomatic skeletal metastases due to prostate
      cancer (PCA). Twenty-five patients with painful osseous metastases due to hormone
      refractory PCA (HRPCA) were treated with 6 mg ibandronate every 4 weeks in an
      open prospective non-randomized clinical study. Primary study endpoint was pain
      reduction documented by the use of a 10-point visual analog scale. Palliative
      response with significant reduction in pain score from 6.5 (5-10) to 2.0 [(0-4),
      P<0.001] was achieved in 23 (92%) patients; nine patients (39%) were completely
      pain free. Bisphosphonate treatment of painful osseous metastases due to HRPCA
      resulted in a significant pain reduction and a significant decrease of daily
      consumption of analgesics in 92% of the patients. Both characteristics are
      paralleled by an increase in Karnofsky index mainly due to better mobility.
      Bisphosphonates should have a definite role in the palliative management of
      symptomatic HRPCA.

PMID- 12496988
TI  - Regulation of Bcl-2 during androgen-unresponsive progression of prostate cancer.
AB  - The progression of prostate cancer from androgen-responsive to an androgen
      unresponsive state remains the greatest obstacle in the treatment of this
      disease. Androgen-unresponsive prostate cancer is highly resistant to
      chemotherapy and radiation treatment that kill cells by the induction of
      apoptosis. Elucidating the molecular mechanisms of apoptosis regulation in
      prostate cancer can be useful in the development of new strategies for effective
      therapy of androgen-unresponsive cancer. We analyzed the Bcl-2 family of
      apoptosis regulators using various passages of the LNCaP prostate cancer cell
      line, which serve as an in vitro model for the progression of prostate cancer
      from androgen-responsive to androgen-unresponsive. In our model, progressively
      higher passages of LNCaP cells represent the progression to androgen
      unresponsiveness. We examined the basal mRNA expression of the Bcl-2 family of
      apoptosis regulators. Under normal growth conditions, both androgen-responsive
      and androgen-unresponsive LNCaP cells express the Bcl-2 family of genes at
      similar levels. Western blot analysis showed the presence of Bcl-2 protein in
      androgen-responsive cells but not in androgen-unresponsive cells. Both androgen
      responsive and androgen-unresponsive cells expressed Bax protein at similar
      levels. When exposed to oxidative stress, androgen-responsive cells underwent
      apoptosis but androgen-unresponsive cells exhibited resistance suggesting that
      the progression to androgen-unresponsiveness was associated with altered
      regulation of apoptosis. Treatment with paclitaxel or sodium butyrate induced
      apoptosis in both androgen-responsive and androgen-unresponsive cells suggesting
      that the apoptotic machinery is still intact in androgen-unresponsive LNCaP
      cells.

PMID- 12496989
TI  - The management of localized prostate cancer.
AB  - At this point in time, the only possibility of curing prostate cancer is through
      the early detection and treatment of localized disease. The large number of
      treatment options available for localized prostate cancer, including radical
      prostatectomy, radiotherapy (either external beam or interstitial), hormone
      therapy and watchful waiting, can be confusing for the patient. These treatments
      are associated with different adverse effects, further complicating the treatment
      decision. As there will inevitably be a trade-off between expected cure and
      acceptable adverse effects, it is important to discuss all options with the
      patient. The doctor and patient must together decide the appropriate treatment
      for him and his tumor.

PMID- 12496990
TI  - The management of locally advanced prostate cancer.
AB  - The current management of locally advanced prostate cancer generally involves
      treatment with radiotherapy, hormone therapy or a combination of both. Of
      particular importance when choosing the type and duration of treatment is the
      patient's risk category, which predicts the risk of subclinical metastases based
      on prostate-specific antigen level, Gleason score and tumor stage. A breakout
      group at the PROstart 2002 workshop, charged with discussing this topic,
      concluded that hormone therapy is a recommended component of disease management
      and may improve survival, and that radiotherapy should be combined with
      neoadjuvant and or adjuvant hormone therapy.

PMID- 12496991
TI  - The value of patient-doctor dialog in the treatment of early prostate cancer.
AB  - A lack of information about the characteristics of prostate cancer, the treatment
      options available, and the negative effects associated with each treatment option
      leaves many newly diagnosed patients feeling anxious, depressed and confused, and
      can ultimately lead to feelings of distrust towards the treating physician.
      Improving patient-doctor dialog increases the chances of successfully achieving
      the patient's goals in managing their disease. Factors considered important for
      improving patient-doctor dialog include an individualized approach to care,
      providing the patient with complete, comprehensive and unbiased information on
      treatment options, and allowing the patient sufficient time to come to a
      treatment decision.

PMID- 12496994
TI  - What's hot in the prostate?

PMID- 12496995
TI  - Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic
      significance of the quinazoline component.
AB  - alpha(1)-Adrenoceptor antagonists, have been documented to induce apoptosis and
      reduce prostate tumor vascularity in benign and malignant prostate cells. The
      quinazoline based alpha(1)-antagonists, doxazosin and terazosin but not
      tamsulosin (a sulphonamide derivative) suppress prostate growth without affecting
      cell proliferation. These quinazoline-mediated apoptotic effects occur via an
      alpha(1)-adrenoceptor independent mechanism potentially involving activation of
      the TGF-beta signal transduction pathway. This review discusses the current
      knowledge of the action of quinazoline-derived alpha(1)-adrenoceptor antagonists
      in the benign and malignant prostate and their potential therapeutic use in the
      treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Finally, a
      molecular pathway is proposed for their observed apoptotic function against
      prostate cells. Increased understanding of the action of these established and
      clinically accepted agents would provide a basis for the design of safe,
      effective therapeutic regimens in the treatment of prostatic diseases.

PMID- 12496996
TI  - Primary cultures of prostate cells and their ability to activate carcinogens.
AB  - Differences in the incidence of prostate cancer (CaP) amongst different migrant
      populations point to causative agents of dietary and/or environmental origin.
      Prostate tissues were obtained following transurethral resection of the prostate
      (TURP) or radical retropubic prostatectomy. After surgery, TURP-derived or tumour
      adjacent tissue fragments were minced in warm PFMR-4A medium (37 degrees C) and
      suspensions pipetted into collagen-coated petri dishes. Non-adherent material was
      removed by washing with fresh medium after 12 h. Adhered cells subsequently
      reacted positively with monoclonal antibodies to prostate specific antigen (PSA).
      PSA was also detected in the medium. The genotoxicities of the chemical
      carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), its N
      hydroxy metabolite (N-OH-PhIP) and benzo[a]pyrene (B[a]P) in adherent cell
      populations from different donors (n=8) were examined. Cells were treated in
      suspension for 30 min at 37 degrees C in the presence of the DNA repair
      inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA single-strand
      breaks were detected in cells by the alkaline single cell-gel electrophoresis
      ('Comet') assay and quantified by measuring comet tail length (CTL) in microm.
      All three carcinogens induced dose-related increases in CTLs (P<0.0001) in cells
      from four donors 24 h post-seeding. However, in cells from a further two donors
      the genotoxic effects of PhIP, N-OH-PhIP and B[a]P were much less apparent after
      48 h than after 24 h in culture. After 96 h in culture, cells from these donors
      appeared to be resistant to the comet-forming activity of the compounds. However,
      B[a]P-DNA adducts were still measurable by (32)P-postlabelling for up to 14 days
      following a 24-h exposure to 50 microM B[a]P in adhered cells from another two
      donors. This study shows that primary cultures of cells derived from the prostate
      can activate members of two classes of chemical carcinogens. Further development
      may provide a robust model system in which to investigate the aetiology of CaP.

PMID- 12496997
TI  - Upregulation of estrogen and androgen receptors modulate expression of FGF-2 and
      FGF-7 in human, cultured, prostatic stromal cells exposed to high concentrations
      of estradiol.
AB  - This study was performed to develop an experimental model in which expression of
      estrogen receptors (ER) by human prostatic stromal cells could be reproducibly
      enhanced relative to similar cells with low ER expression. The second aim was to
      characterise changes in expression of ER, androgen receptor (AR), FGF-2 and FGF-7
      in stromal cells exposed to high and low concentrations of estradiol and
      testosterone mimicking the different sex hormone levels between young and elderly
      men. Five strains of human prostatic stromal cells, isolated from BPH resections,
      were grown in steroid-free medium plus 1 micromol 17beta-estradiol. After 10
      days, cells were passaged and grown in the same medium without estradiol until
      confluent. In a second study four cell strains were exposed to high and low
      concentrations of 17beta-estradiol and testosterone for 10 days. Cells were
      labelled with fluorescent antibodies to ERalpha, AR, FGF-2 and FGF-7 and the
      fluorescence intensity measured by flow cytometry. Following exposure to 1
      micromol estradiol, stromal cells showed reduced expression of AR and ERalpha but
      after passage without estradiol they showed a 25% increase in both receptors over
      controls. Different combinations of sex hormones induced inconsistent changes
      with respect to expression of ER, AR and FGFs in the various cell-strains.
      However, there was a highly significant correlation between AR, ER and FGF-2 and
      FGF-7, which was cell strain-specific. Thus, changes in sex hormone balance per
      se may not be solely responsible for the observed increases in prostatic ER
      levels in BPH. Since expression of ER is correlated with synthesis of FGF-2 and
      FGF-7, it is likely that increases in stromal ER may mediate the synthesis of
      stromally-derived growth factors which contribute to the aetiopathogenesis of
      benign prostatic hyperplasia.

PMID- 12496998
TI  - Clearance rates of total prostate specific antigen (PSA) after radical
      prostatectomy in African-Americans and Caucasians.
AB  - Racial differences in serum prostate specific antigen (PSA) values in men with
      and without prostate cancer have been observed but have yet to be explained. We
      aimed to determine if ethnic variations in the rate of metabolism of PSA could
      explain the different levels of PSA found in African-American and Caucasian men.
      In a prospective fashion, patients diagnosed with biopsy-proven clinically
      localized adenocarcinoma of the prostate and scheduled for radical prostatectomy
      were selected for the study. Eleven patients (six Caucasian, five African
      American) were enrolled in the study. All patients demonstrated normal liver and
      renal function. Sera for total PSA were obtained at the following time intervals:
      preoperative (within 3 months of operation), time 0 (at time of prostate
      removal), 1, 4, 8, 24, 48, 72, 168 and 336 h after removal of the prostate. A log
      linear regression model was then used to determine the metabolic clearance rate
      and half-life of serum total PSA. There were no statistically significant
      differences between Caucasian and African-American patients with regard to age,
      PSA prior to surgery, prostate weight, Gleason sum and PSA half-life. The
      metabolic clearance of total PSA followed first order kinetics. When comparing
      serum PSA levels expressed as a fraction of the baseline PSA, Caucasian and
      African-American patients demonstrated similar rates of metabolism. This study
      found similar rates of elimination of serum total PSA between African-Americans
      and Caucasians. These findings suggest that the rate of metabolism of PSA is
      similar for these groups. Further studies are needed to explain racial
      differences of serum PSA in patients with and without prostate cancer.

PMID- 12496999
TI  - Probability of prostate cancer at various levels of per cent free prostate
      specific antigen in Japanese men with total PSA of 4.1-10.0 ng/ml.
AB  - Estimates for the likelihood of prostate cancer at different levels of per cent
      free prostate specific antigen (PSA) were derived from experience with
      consecutive Japanese male patients with intermediate total PSA values who
      underwent ultrasound-guided biopsies and/or transurethral resection of the
      prostate. Receiver operating characteristic (ROC) curve analysis showed that in
      patients with a total PSA of 4.1-10.0 ng/ml, per cent free PSA identified those
      with prostate cancer better than did total PSA; per cent free PSA also proved
      superior in the subgroup whose glands appeared benign on palpation. The
      probabilities of prostate cancer at per cent free PSA values of <or=10.0, >10-15,
      >15-20, >20-26 and >26% were 58.3, 40.8, 25.3, 14.3 and 7.6%, respectively, when
      analyzed without regard to findings on palpation. In patients with palpably
      benign glands, the corresponding values were 55.3, 35.4, 19.6, 9.7, and 4.6%,
      respectively. These probabilities are lower than those reported in Western
      countries, probably reflecting both different patterns of practice and racial
      differences. Race-specific assessment is recommended before applying a clinical
      test.

PMID- 12497000
TI  - Distribution of vascular endothelial growth factor (VEGF) in prostate disease.
AB  - Vascular endothelial growth factor (VEGF) is a heparin-binding polypeptide growth
      factor. It is a potent mitogen for endothelial cells. Immunohistochemical
      localisation of VEGF was performed on 25 moderate to poorly differentiated stage
      T4 M+ prostate cancer specimens and 30 benign prostatic hyperplasia (BPH)
      specimens. A positive result was indicated by area staining >25% and +2 or +3
      staining intensity. Positive epithelial staining was observed in 50% of BPH
      specimens and 56% of cancer specimens, while positive stromal staining was
      observed in 73% of BPH specimens and 30% of cancer specimens. This may reflect an
      active role for stromal VEGF in the pathological process of BPH.

PMID- 12497001
TI  - Microvessel density in prostate carcinoma.
AB  - The objective of this work was to assess the correlation between microvessel
      density (MVD), pathological stage and disease recurrence in a series of patients
      who underwent radical prostatectomy for prostate cancer. Pathological material
      from 75 consecutive radical prostatectomies performed before 1994 without neo
      adjuvant treatment, in which sufficient follow-up data were available, was re
      examined. Paraffin embedded material was re-cut and hematoxylin and eosin (H&E)
      stained. Areas of maximal angiogenesis within tumor were identified. Expression
      of CD34 was investigated by using the monoclonal antibody MY 10. Within the areas
      of maximal angiogenesis, microvessels expressing CD34 were counted and specimens
      were divided into two groups, one showing a count of less than 90 microvessels
      per microscopic field at 200 x magnification (MVD<90), the second more than 90
      microvessels (MVD>90). The MVD was then related to pathological stage, Gleason
      score (GS) and outcome of the disease. Mean follow-up was 84 months. Clinical or
      biochemical progression was observed in 38.6% of patients. In low GS cases, MVD
      was always <90, whereas in GS 5-6, half had MVD <90 and half were >90. In high GS
      MVD was always >90. MVD was positively associated with a higher pathological
      stage. Progression of the disease was observed in 20% of MVD <90 and in 51% in
      MVD >90 (P=0.006). Mantel-Haensz test showed a correlation between MVD and time
      to progression (P<0.05). Although problems exist in methods of counting and in
      the cut-off number of vessels, which can discriminate the risk categories, it may
      be concluded that microvessel counts, using CD34 monoclonal antibody, can
      accurately predict the outcome of radical prostatectomy.

PMID- 12497002
TI  - Caffeine test in predicting flutamide-induced hepatic injury in patients with
      prostate cancer.
AB  - The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a
      major enzyme involved in the activation of flutamide. The usefulness of this test
      in predicting flutamide-induced hepatic injury in patients with prostate cancer
      was examined. The subjects were: (1). five patients whose aspartate
      aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l
      or higher following the start of flutamide (moderately injured group); (2). four
      patients whose AST and ALT levels were higher than normal but less than 100 IU/l
      (mildly injured group); and (3). two patients whose hepatic function remained
      normal (normal group). The subjects were each given canned coffee to drink.
      Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U)
      levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was
      calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for
      the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/
      1.42) were lower than that for the normal group (9.56). The results suggest that
      a decrease in CYP1A2 activity is involved in the onset of flutamide-induced
      hepatic injury, and that the caffeine test seems to provide a useful means of its
      prediction.

PMID- 12497003
TI  - Evaluation of preoperative ProstaScint scans in the prediction of nodal disease.
AB  - Diagnostic methods are limited for detecting microscopic soft tissue metastases
      in patients with prostate cancer. Previous studies using (111)Indium Capromab
      Pendetide (ProstaScint scan) analyzed patients with extensive localized tumor
      (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We
      evaluated the role of the ProstaScint trade mark scan in a preoperative
      population to provide histological documentation and to assess its utility in a
      surgical population. A total of 22 preoperative patients, underwent a ProstaScint
      scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9-33 ng/ml). The mean
      Gleason score at biopsy was 6.9 (range 6-9). Each patient underwent a radical
      retropubic prostatectomy and bilateral pelvic lymph node dissection, which
      included resection of both obturator and common iliac lymph nodes. Histologic
      analysis of the resected lymph nodes provided the standard of comparison with the
      ProstaScint scan. The results of the scan and pathology for all 22 patients were
      compared with the bilateral obturator and iliac nodes, creating 88 data points.
      Nine areas (10%) were positive on the scan. One of these (11%) was a true
      positive while the other eight (89%) were false positives. Seventy-nine areas
      (90%) were negative on scan results. Of these, five areas (6%) were false
      negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity
      of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive
      predictive value (PPV) of 11%. The high false positive rate and low PPV of
      ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful
      when used preoperatively.

PMID- 12497004
TI  - Initiation of salvage therapy for prostate cancer.
AB  - Physicians and patients have variable and individual levels of comfort regarding
      when to begin salvage therapy for rising prostate specific antigen (PSA) after
      definitive treatment of prostate cancer. The decision to start salvage therapy is
      a multifactorial process for which few rigorous data or guidelines exist. A
      questionnaire survey of urologists of the Department of Defense (DoD) Center for
      Prostate Disease Research (CPDR) was undertaken to obtain current perspectives on
      when to begin salvage therapy for biochemical failure after definitive therapy.
      Variables of age, grade, T-stage, nodal status, performance status, latency since
      prior therapy, PSA velocity, and ploidy were prioritized in four clinical
      situations; subsequent questions assessed consensus PSA cut-offs for beginning
      adjuvant therapy in 84 clinical scenarios. Consensus on PSA cut-off points was
      limited to postoperative radiotherapy (RT), where values of 1.0-1.5 were the mean
      cut-off points. CPDR urologists consider salvage prostatectomy post-RT only for
      patients <70-y-old with node negative, grade 2-7 disease and excellent
      performance status. Ploidy was not generally considered useful in any scenario.
      Many variables in addition to PSA level are involved in the decision of when to
      commence adjuvant therapy for initial biochemical failure. These are strikingly
      interdependent, and few clear absolutes are evident from this questionnaire. This
      is a point of necessary further research and continued discussion among
      physicians caring for these patients.

PMID- 12497005
TI  - The comparative values of bone marrow aspirate and trephine for obtaining bone
      scan-targeted metastases from hormone-refractory prostate cancer.
AB  - Samples of metastatic prostate cancer to bone are difficult to obtain. The aim of
      this study was to compare the results of bone marrow aspirate and trephine biopsy
      for obtaining metastatic hormone-refractory prostate cancer (HRPC) samples using
      previous diagnostic planar 99(m)Tc-HDP bone scans to guide the procedure. All
      samples taken were for the purposes of research and molecular studies on HRPC.
      Twenty patients with HRPC had bone marrow aspirate and trephines taken from
      lesions in the posterior superior iliac spine or sacro-iliac region when shown on
      diagnostic 99(m)Tc-HDP bone scans. Three patients also underwent plain X-ray, 18F
      positron emission tomography bone scan, pelvic MRI scan and 99(m)Tc nanocolloid
      bone marrow scans. These images were used to assess if the extra imaging
      information provided, such as three-dimensional localisation of the bone
      metastases, was of value for target bone metastases. Cancer cells were obtained
      in 15/20 (75%) cases in which a trephine biopsy was attempted and 0/20 of cases
      in which a bone marrow aspiration was attempted. The additional information
      provided by the range of other imaging investigations was of little benefit in
      obtaining tumour samples, but did suggest why negative biopsies were obtained in
      some cases after targeting with planar bone scans. We recommend the use of bone
      marrow trephine biopsy alone, guided by previous diagnostic 99(m)Tc planar bone
      scan as a practical method to obtain prostate cancer cells from bone metastases.

PMID- 12497006
TI  - Primary hormonal therapy for prostate cancer: experience with 135 consecutive PSA
      ERA patients from a tertiary care military medical center.
AB  - The use of prostate specific antigen (PSA) in the 1990s has brought on a stage
      migration of prostate cancer. Despite that, many men have still presented with
      metastatic prostate cancer in the past decade. The use of primary hormone therapy
      in the PSA era at a tertiary care Army Medical Center is studied in this paper.
      Charts were reviewed of 135 men who were diagnosed with metastatic prostate
      cancer and treated with hormone therapy as a primary treatment between 1989 and
      1995. Statistical analysis was used to determine significant predictor variables
      on the time to disease progression. In univariate analysis clinical stage,
      pretreatment alkaline phosphatase and nadir PSA values were significant
      predictors of time to progression. Race and type of treatment were not. In
      multivariate analysis the relative risk of progression was 3.2 for patients with
      an alkaline phosphatase >252 and 16.5 for patients with a nadir >2.0. This study
      supports the argument that racial disparities in prostate cancer outcomes are due
      to access to care. Furthermore, the survival rate for patients with D-2 disease
      is better than in the pre PSA studies. Clinical stage, pretreatment alkaline
      phosphatase and PSA nadir can be used to predict response for those men
      presenting with metastatic prostate cancer.

PMID- 12497007
TI  - Clinical significance of pulmonary metastases in stage D2 prostate cancer
      patients.
AB  - Several prognostic factors such as the extent of bone metastases (EOD) in
      advanced prostate cancer (PCa) have been reported. Metastasis of the lung is
      rarely a significant clinical factor in the management of prostate cancer. The
      present study evaluates the clinical significance of lung metastases. We
      retrospectively reviewed the PCa database to identify patients with pulmonary
      metastases at initial diagnosis. The medical records of the patients were
      examined with respect to age, histologic grade, EOD score, marker response to
      endocrine therapy and clinical outcome. We then compared several potential
      clinical factors between patients with and without pulmonary metastases. Next, we
      retrospectively reviewed autopsy records of 60 Japanese patients who died of
      hormone-refractory metastatic PCa with particular focus upon metastatic profiles.
      A comparative study of stage D(2) patients with (n=20) and without (n=77)
      pulmonary metastases found no significant differences in EOD score, performance
      status, marker response and survival. Only tumor grade was better in the group
      with, than without pulmonary metastases (P=0.0120, chi-square analysis). In the
      series of autopsies, we found pulmonary metastases in 38 cases (63%), following
      metastases of the bone (57 cases, 95%) and lymph nodes (52 cases, 87%). A
      retrospective analysis of survival showed that patients with bone or lymph node
      metastases had a positive relative risk. In contrast, lung metastasis could be a
      positive prognostic indicator, although the findings were not statistically
      significant. These data suggest that the presence of pulmonary metastasis has no
      ominous impact on clinical course and disease outcome even in patients with
      disseminated prostate cancer.

PMID- 12497008
TI  - Adenocarcinoma of the prostate: an expensive way to die.
AB  - The costs of radical prostatectomy and radiation therapy for localized carcinoma
      of the prostate are well known, the costs of terminal care for men with
      metastatic disease less so. We sought to determine the costs of terminal care
      incurred with prostate cancer in the last year of life. A retrospective chart
      review was conducted at five military medical centers identifying 32 patients who
      had died from prostate cancer from 1995 to 1997. The data investigated were:
      duration of metastatic disease, days hospitalized in the last year of life,
      palliative procedures (surgery or radiation), chemotherapy and need for
      transfusions. The mean duration of symptomatic metastatic disease was 3.4 y. The
      mean duration of hospitalization in the last year of life was 19 days. Seven
      patients (22%) required channel transurethral resection of the prostate (TURP).
      Three patients (9%) required either percutaneous nephrostomies or stenting. The
      mean number of transfusions required was 5.4. Eighteen patients (56%) underwent
      bilateral simple orchiectomy (BSO), 14 (44%) used LHRH agonists and 11 (34%) used
      anti-androgens. The mean total cost of hospitalization, studies, outpatient
      visits to physicians, palliative procedures and hormonal therapy was US dollars
      24660 in the last year of life. Comparatively, the cost of radical prostatectomy
      is US dollars 12250 and three-dimensional conformal radiation therapy is US
      dollars 13823. Our estimation of costs due to metastatic disease is at best an
      underestimation. Men dying of prostate cancer incur significant costs in the last
      year of life. Based upon recent epidemiological data the cost of death due to
      prostate cancer in the US is over three quarters of a billion dollars a year.

PMID- 12497009
TI  - Innovators in Urology, 4th International Meeting. 9-11 March 2002, Miami,
      Florida, USA. Abstracts.

PMID- 12497017
TI  - Editorial.

PMID- 12497016
TI  - What's hot in the prostate?

PMID- 12497018
TI  - Is there a role for antiandrogen monotherapy in patients with metastatic prostate
      cancer?
AB  - Castration is the most widely used form of androgen ablation employed in the
      treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen
      monotherapy is a potential alternative treatment option for men for whom
      castration is unacceptable or not indicated. Of the three non-steroidal
      antiandrogens, bicalutamide ('Casodex'), flutamide and nilutamide, only
      bicalutamide has been compared with castration in large, controlled, randomised,
      Phase III trials in M1 patients. A post-hoc analysis of these studies indicated
      that bicalutamide 150 mg/day monotherapy may be of benefit to M1 patients with a
      prostate specific antigen (PSA) level </=400 ng/ml. Significant advantages for M1
      patients treated with bicalutamide were observed in subjective response rate,
      maintenance of sexual interest and physical capacity. Patients with a higher
      disease burden (PSA >400 ng/ml) may decide that quality of life and symptomatic
      benefits outweigh the slight survival disadvantage seen in clinical trials and
      opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer
      and Prostatic Diseases (2001) 4, 196-203.

PMID- 12497019
TI  - Hormone-refractory prostate cancer: a multi-step and multi-event process.
AB  - Since the pioneering studies of Huggins in 1941, it has been known that prostate
      cancer cells, like certain normal epithelial cells, can chronically depend on a
      critical level of androgenic stimulation for their continuous growth and
      survival. The entire issue of the development of resistance to androgen ablation
      therapy for metastatic prostate cancer is based on the fact that a portion of
      cells can survive without androgen stimulation. The cell mechanism of androgen
      independent status is unclear. For some authors, a portion of the cells present
      within a patient with a prostate cancer before therapy is naturally androgen
      independent (selection hypothesis). However, this hypothesis does not consider
      gene alteration during prostate cancer natural history and probably hormone
      refractory prostate cancer (HRPC) is due to a multi-step and multi-event process.
      In this literature review, different cell pathways that lead to HRPC are
      described.Prostate Cancer and Prostatic Diseases (2001) 4, 204-212.

PMID- 12497020
TI  - The relationship between quality and costs: factors that affect the hospital
      costs of radical prostatectomy.
AB  - The present study seeks to establish a relationship between the quality of a
      surgical procedure and the subsequent hospital costs for that procedure by
      investigating the influence of both patient and peri-operative factors on the
      hospital costs of radical prostatectomy. All men who underwent radical
      prostatectomy at one institution during an 18-month period were included in this
      study. Clinical information was obtained from medical records and cost
      information was obtained from hospital billing data. The medical record was also
      used to determine peri-operative information such as operating room time,
      anesthesia time, surgical time, blood loss and units of packed red blood cells
      transfused. The correlation between costs and both clinical and peri-operative
      factors were determined using the Pearson correlation co-efficient. One hundred
      and four men underwent radical prostatectomy at our institution during the time
      period studied. Mean age of these patients was 60.2 y and mean length of stay for
      these patients was 3.4 days with a range of 2-10 days. Mean total hospital costs
      for this cohort was $5305 with a range of $2851-$10 358. Significant correlations
      with total hospital costs included operating room time, surgical time, estimated
      blood loss and blood transfused. Patient factors such as age, ASA class, co
      morbidities and smoking history were not correlated with total hospital costs.
      The present study demonstrates that factors at least partially controlled by the
      surgeon such as surgical time and units of blood transfused directly influence
      the total hospital costs of radical prostatectomy, while patient factors such as
      age and the presence of co-morbidities had no significant correlation with total
      hospital costs. These findings demonstrate that surgeons can impact health care
      costs by providing high quality care and begins to establish a relationship
      between high quality care and low cost care.Prostate Cancer and Prostatic
      Diseases (2001) 4, 213-216.

PMID- 12497021
TI  - Could we measure the efficiency of prostate cancer treatment? A critical
      appraisal of economic evaluation studies.
AB  - The objective of this paper is to introduce the methodology of economic analysis
      in health care, and its application to the measurement of the efficiency analysis
      of prostate cancer treatment. We presented the methodology of economic analysis.
      To review its application in prostate cancer treatment, we performed a
      bibliographic search in the main biomedical databases (February 1988-January
      2001) to identify economic evaluation studies that compared both costs and
      effects of prostate cancer treatments. The lack of economic studies for localized
      prostate cancer and the diversity of treatments for advanced prostate cancer make
      it difficult to make comparisons across studies and to make therapeutic
      recommendations.Prostate Cancer and Prostatic Diseases (2001) 4, 217-220.

PMID- 12497022
TI  - TNF-alpha protects dendritic cells from prostate cancer-induced apoptosis.
AB  - We have recently shown that human prostate cancer (PCa) cells induced apoptotic
      death of the most potent antigen-presenting cells, dendritic cells (DC), which
      are responsible for the induction of specific antitumor immune responses. Here we
      have evaluated the effect of murine PCa cells RM-1 on the survival of immature
      and tumor necrosis factor-alpha (TNF-alpha)-stimulated mature DC. PCa cells and
      DC were co-incubated for 24-48 h and DC apoptosis was assessed by morphologic
      criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation
      of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which
      was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation
      of DC maturation by TNF-alpha resulted in increased resistance of DC to PCa
      induced apoptosis. In TNF-alpha treated mature DC, but not in immature DC, the
      expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus,
      these data suggest that TNF-alpha-induced maturation of DC increases their
      resistance to PCa induced apoptosis. This is likely to be due to the stabilizing
      of the expression of anti-apoptotic protein Bcl-2. The difference in the
      sensitivity of mature and immature DC to PCa-induced cell death should be
      considered during the design of DC-based clinical trials for PCa
      patients.Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

PMID- 12497023
TI  - Influence of circumcision and sexual behaviour on PSA levels in patients
      attending a sexually transmitted disease (STD) clinic.
AB  - Early age at first intercourse, increased number of sexual partners, lack of
      circumcision and history of sexually transmitted diseases (STDs) are associated
      with prostate cancer. There has been no investigation of the effect of these
      factors on prostate health at an early age. Previously collected serum samples
      from STD clinic attendees were tested retrospectively for anti-chlamydial
      antibodies, and prostate specific antigen (PSA) concentration. Patients at an STD
      clinic were interviewed regarding age of first intercourse, number of sexual
      partners and circumcision status. This was compared to clinical diagnosis, anti
      chlamydial antibody titre and PSA concentration. The results showed: (1) that of
      patients with an anti-chlamydial antibody titre equal or greater than 1 in 64
      (n=27) 37% had a PSA concentration greater than 0.8 ng/ml while those with a
      titre less than 1/64 (n=201) only 17% had a PSA >0.8 (P<0.05). (2) No association
      was found with circumcision status. (3) Early age of first intercourse and more
      than 20 sexual partners were associated with a synergistic increase in mean anti
      chlamydial antibody titre and a mean PSA concentration of 1.2 ng/ml (95% CI 0.56
      1.76). It is concluded that these results provide the first evidence that sexual
      behaviour related risk factors for prostate cancer do damage the prostate at an
      early age. Though they do not prove that infection is a cause of prostate cancer
      they do justify further research into the specificity of agents involved and
      impact of antibiotic treatment.Prostate Cancer and Prostatic Diseases (2001) 4,
      228-231

PMID- 12497024
TI  - Association between serum triiodothyronine (t3) level and risk of disease
      recurrence in men with localized prostate cancer.
AB  - We assessed the relationship of serum triiodothyronine (t3) level and risk of
      disease recurrence in men treated for 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 had been initially
      diagnosed on the basis of rising prostate specific antigen (PSA) or abnormal
      physical examination. Histological confirmation of diagnosis was obtained for all
      subjects. Serum (t3) level was determined by chemoluminescent assay with a
      standard, commercially available instrument (Immulite Diagnostic Products
      Corporation, Los Angeles, California). Sixty-eight men with prostate cancer were
      studied. In our treatment protocol, patients are divided into three risk groups:
      low risk: serum PSA</=10, stage</=T2a, or Gleason grade</=6. These patients are
      treated with a radioactive implant; moderate risk: serum PSA 10-15 or Gleason 7
      or stage</=T2b. These patients are treated with 3 months of combined hormonal
      therapy followed by an implant; high risk: Gleason >7, tumor in seminal vesicle
      biopsy, serum PSA >15 or stage T2c or T3. These patients are treated with 3
      months combined hormonal therapy, an implant, and after 2 months break 6000 rad
      external beam radiotherapy. There was a significant increase in serum t3 with
      risk category (P=0.011). Tukey's multiple range B-test showed a significant
      difference between the t3 levels of the high risk patients, when compared to the
      t3 levels of the moderate (P=0.013) and low risk patients (P=0.041). The range
      test showed no significant difference between the t3 levels of the moderate and
      low risk patients (P=0.897). Because t3 levels may be affected by age, we
      performed multivariate linear regression, with t3 as the dependent variable.
      There was a statistically significant (P=0.035) association of t3 level with risk
      group, but there was no significant association of t3 with age (P=0.803).
      Multivariate linear regression, with t3 as dependent variable, PSA, Gleason
      score, and stage as independent variables showed a significant overall
      association of the three independent variables with t3 (P=0.042), though
      individually the relationships were not significant. None of the men had a t3
      level that was above the normal range for our laboratory (137 ng/dl). Urologists
      are actively seeking additional biomarkers of prostate cancer aggressiveness.
      Many prostate cancers are quite indolent and may never cause a problem, but it is
      impossible to identify such tumors with certainty. Further studies of serum t3
      level as a biomarker in prostate cancer might therefore be worthwhile. With more
      and better biomarkers, many older men might be spared the rigors of radiation
      therapy and/or surgery and the complications. Also, new prostate cancer therapies
      might be directed toward inhibiting the mitogenic effects of t3.Prostate Cancer
      and Prostatic Diseases (2001) 4, 232-234.

PMID- 12497025
TI  - Attitudes and use of alternative therapies in UK prostate cancer patients-isn't
      it time we were in the know?
AB  - With increasing media interest in prostate cancer and the availability of data to
      patients from support groups and the Internet, the knowledge and use of
      alternative therapies by patients is becoming more common. The purpose of our
      study was to quantify patient awareness and use of alternative therapies for the
      prevention and treatment of prostate cancer in the UK. In May 2000, we performed
      a survey of men attending our urology outpatient clinic for prostate cancer
      evaluation or follow-up. All men diagnosed with and those at high risk (abnormal
      prostate specific antigen) for prostate cancer were eligible for the study. Each
      eligible patient was then sent an anonymous 25-item questionnaire to explore
      their knowledge and use of various alternative therapies for prostate cancer. Out
      of 195 patients who were sent the questionnaire, 168 responded, for a response
      rate of 86%. One hundred and sixty-four were analysed. Eight-two out of 164 (50%)
      were aware of alternative therapies for prevention/treatment of prostate cancer,
      the most common were tomatoes/tomato-based products and low-fat diet. There were
      27 (16.5%) respondents taking alternative therapies for their prostate. Private
      patients were more aware (60.4% private vs 46.2% NHS) of complimentary therapies
      and were more likely to take them (27.9% private vs 12.4% NHS) than National
      Health Service patients. The majority of patients (60%) had not informed their GP
      or urologist. Fifteen therapies and 12 medication sources were recorded. Asked if
      doctors should discuss non-prescribed therapies, even if there is no proven
      benefit, 62% said 'yes' while 29% said 'no'. Alternative therapy use for prostate
      cancer is likely to increase. If we don't ask patients specifically whether they
      are taking them, patients are unlikely to tell us. Urologists and clinical
      oncologists treating men with prostate cancer need to be aware of alternative
      therapies and have some understanding of any benefit or harm, not only to be able
      to answer patient's questions and offer advice, but also to consider interactions
      with other treatments.Prostate Cancer and Prostatic Diseases (2001) 4, 235-241.

PMID- 12497026
TI  - Comparative early results of the sandwich technique and transurethral
      electroresection in benign prostatic hyperplasia.
AB  - No study has yet reported the comparative results of the sandwich technique and
      transurethral electroresection in the management of benign prostatic hyperplasia.
      Thirty patients with benign prostatic hyperplasia were divided into two groups,
      each consisting of 15 patients. The first group underwent the sandwich technique
      (transurethral electrovaporization-transurethral electroresection-transurethral
      electrovaporization) and the second group had transurethral electroresection
      alone (TURP). Preoperatively all patients underwent a digital examination and the
      determination of prostatic volume by transrectal ultrasonography, and a symptom
      score (IPSS), the maximal flow rate (Q (max)), post-void residual urine (PVR).
      Six months after the operation, all the variables were remeasured and the values
      compared with those before treatment and between the groups. The improvements in
      symptom score, residual urine and maximum flow rate were slightly better after
      the sandwich technique than after TURP but the differences between the two groups
      were not statistically significant. Additionally, lower amounts of irrigant
      solution were used (P>0.05) and operative time was shorter in the sandwich group
      (P>0.05). Although the duration of catheterization in the sandwich group was
      lower than that of the TURP group (1.6 and 2.26 days respectively (P<0.05)),
      three patients (20%) required catheterization. Although the improvements in the
      objective parameters 6 months after, early indications showed that the sandwich
      technique results were almost the same as after TURP. There might be several
      advantages of this technique, particularly the fact that no blood transfusion is
      required and earlier removal of urethral catheter.Prostate Cancer and Prostatic
      Diesases (2001) 4, 242-244.

PMID- 12497028
TI  - Keyword Index to Volume 4.

PMID- 12497029
TI  - What's hot in the prostate?

PMID- 12497030
TI  - Editorial.

PMID- 12497031
TI  - A quantitative analysis of the costs and benefits of prostate cancer screening.
AB  - The present study attempts to quantitate in an economically and clinically
      meaningful manner the cost and cost-effectiveness of prostate cancer screening
      and subsequent treatment, including complications from that treatment. Outcome
      data from large prostate cancer screening trials using prostate specific antigen
      (PSA) and digital rectal examination (DRE) and PSA alone were used to construct
      the screening model. The benefit of screening is expressed in years of life saved
      by screening, which is calculated by comparing the survival rate of men with
      prostate cancer to the survival rate of men in the general population. The cost
      of screening, treatment, and complications were estimated using the Medicare data
      base and published reports on the cost, morbidity and mortality for radical
      prostatectomy. The cost per year of life saved by prostate cancer screening with
      PSA and DRE was $2339-3005 for men aged 50-59, $3905-5070 for men aged 60-69, and
      $3574-4627 overall for men aged 50-69. The cost per year of life saved by
      prostate cancer screening with PSA alone for men aged 50-70 was $3822-4956. A
      sensitivity analysis demonstrates that the cost per year of life saved by
      prostate cancer screening will not change substantially even if the assumptions
      in this model have been underestimated or overestimated by 100%. This study
      quantifies only those parameters which can be reliably compared in concrete terms
      such as dollars, treatment impact on survival, published complication rates and
      published treatment costs. Using this type of analysis, prostate cancer screening
      appears to be a cost-effective intervention. However, the issue of whether
      prostate cancer screening is cost-effective will be decided definitively only
      when randomized, controlled trials are available to quantify the costs and
      benefits of prostate cancer screening.Prostate Cancer and Prostatic Diseases
      (2001) 4, 138-145.

PMID- 12497032
TI  - Prostate specific antigen density. Is there a role for this parameter when
      screening for prostate cancer?
AB  - The objective of this paper is to validate prostate specific antigen (PSA)
      density (PSAD) routine use to enhance PSA specificity in men with normal digital
      rectal examination and intermediate PSA values. It is a retrospective study of
      235 men from a prostate cancer (PCa) screening program. All of them presented PSA
      values between 4 and 10 ng/ml, normal digital rectal examination, and a
      transrectal ultrasound (TRUS) guided biopsy available (PSA>/=4 ng/ml as the sole
      criterion for biopsy). Multivariate analysis failed to demonstrate higher PSAD
      values in men with PCa. PSAD cutoff points higher than 0.07 ng/ml per cc were
      considered as unacceptable, with less than 95% sensitivity. When a cutoff point
      of 0.15 was considered, as many as 30.6% of the cancers were missed. In
      conclusion we cannot recommend the use of this parameter for the above mentioned
      purpose.Prostate Cancer and Prostatic Diseases (2001) 4, 146-149.

PMID- 12497033
TI  - KAI1 expression can be a predictor of stage A prostate cancer progression.
AB  - The disease progression and rate of cancer death were analyzed in 52 patients
      with stage A prostate cancer who underwent transurethral resection of the
      prostate (TURP) or retropubic subcapsular prostatectomy (SCP) between 1987 and
      1998. We performed immunohistochemistry on 16 patients to determine the
      correlation between the expression of the tumor metastasis suppressor gene KAI1
      and the subsequent progression of stage A prostate cancer. Nineteen and 33 of the
      patients had cancer at stage A1 and stage A2, respectively, and their subsequent
      courses were followed for an average of 53.7 months (24-134 months). Progression
      to clinical cancer was found in six patients (one with stage A1, and five with
      stage A2). This progression was evident 40.8 months (5-80 months) after TURP or
      SCP. Four (66.7%) of the patients died of cancer progression (average 31 months)
      after prostatectomy. All four patients had stage A2, poorly differentiated
      adenocarcinoma, and had been followed with administration of diethylstilbestrol
      diphosphate (DES-P). The disease-free patients (n=10) showed overexpression of
      KAI1 protein, compared to those with disease progression (n=6). These results
      indicate that progression arose mainly in the patients with stage A2 cancer, and
      that poorly differentiated, focal and weak expression of KAI1 protein is highly
      associated with disease progression. It is suggested that patients in this group
      should be treated with immediate total androgen blockade, radiation, or radical
      prostatectomy after diagnosis.Prostate Cancer and Prostatic Diseases (2001) 4,
      150-153.

PMID- 12497034
TI  - A population-based study on management of prostate cancer in four regions of
      France.
AB  - In France, as in other European countries, management of prostate cancer in the
      population is rather variable. The objective was to analyse diagnosis and
      treatment modalities of prostate cancer in patients from French cancer
      registries.A sample of 803 patients with prostate cancer diagnosed in 1995 was
      drawn at random from cases recorded in four cancer registries in the geographical
      regions of Bas-Rhin, Calvados, Isere and Tarn. Diagnosis, clinical staging and
      treatment were analysed by questionnaire. Multivariate analysis by logistic
      regression was used to describe medical determinants (age, PSA, clinical staging)
      of the various treatment choices.The mean age of the patients was 71.6 y (range
      46-94 y). Clinical staging showed 60% T(1-2) tumours, 15% T(3-4) and 17% N+or
      metastases. PSA rate (median 18.2 ng/ml) was assessed in 92.4% of patients.
      Prostate cancer was diagnosed by prostate biopsy in 63% and by transurethral
      resection of the prostate (TURP) in 32% of patients. The main treatments were
      radical prostatectomy 22%, radiotherapy 19.4%, hormonal therapy 33%, TURP alone
      17.7% and expectant management 6%. The method of treatment was unknown in 5.7% of
      cases. Adjuvant radiotherapy or hormonal therapy had been used in 31% of cases.
      Logistic regression analysis showed that radical prostatectomy was most often
      performed in patients aged <60 y, three times more frequently for T(2) tumour and
      for PSA between 4 and 20 ng/ml. Radiotherapy was the most frequently applied
      treatment for patients aged between 65 and 75 y, especially in T(3)
      tumours.Approximately 75% of the patients in the study underwent a specific
      treatment for prostate cancer with a curative intention in 40%. This study
      provides a baseline to clinicians and public health authorities on the management
      of prostate cancer in France with recent data. This survey will be useful to
      compare future descriptive analysis and to provide data regarding changing
      clinical practice.Prostate Cancer and Prostatic Diseases (2001) 4, 154-160.

PMID- 12497035
TI  - Bone loss associated with the use of LHRH agonists in prostate cancer.
AB  - Hypogonadism is a recognised cause of osteoporosis in men. When patients with
      advanced prostate cancer are treated with luteinising hormone releasing hormone
      (LHRH) agonist analogues their circulating testosterone levels decline and these
      patients may develop fractures.We have undertaken a cross-sectional study on a
      cohort of patients treated with goserelin (n=41) and compared their bone density
      and bone turnover with patients with prostate cancer not on goserelin and elderly
      patients living in the community.There was no difference in bone density between
      the patients on treatment and those living in the community and there was a
      similar incidence of osteoporosis (50 and 42%, respectively). The bone marker
      measurements were higher in the treated patients: urine N-telopeptide (NTX) 80.1
      (9) (mean (s.e.)) BCE/mmol, compared to 30.1 (2.9), P<0.001 in elderly patients;
      and bone alkaline phosphatase 41.9 (6.1) u/l in treated patients and 20.7 (1.5)
      in untreated prostate cancer patients, P<0.002. Patients on treatment with
      radionuclide scan evidence of metastases did not have higher bone marker values
      than those with negative scans.As increased bone turnover and low bone density
      are associated with enhanced risk of osteoporotic fractures, we suggest that
      patients on LHRH agonist analogues should receive advice and possibly anti-bone
      resorptive treatment with bisphosphonates to prevent further bone loss and
      fractures.Prostate Cancer and Prostatic Diseases (2001) 4, 161-166.

PMID- 12497036
TI  - Validity of PSA, free/total PSA ratio and complexed/total PSA ratio measurements
      in men with acute urinary retention.
AB  - The reliability of serum prostate specific antigen (PSA) measurements in men with
      acute urinary retention is unclear. Total PSA, free and complexed PSA were
      measured, and the free/total (f/t) PSA and complexed/total (c/t) PSA ratios
      calculated, prior to catheterisation and at 48 and 72 h post-catheterisation in
      39 men with acute retention. Subsequent histology showed 12 patients had prostate
      cancer and 27 benign prostatic hypertrophy. Serum free and total PSA fell
      following catheterisation, while complexed PSA rose during the first 48 h then
      subsequently fell. The f/t PSA and c/t PSA ratios provided the best
      discrimination at 48-72 h with 100% sensitivity and 75-82% specificity.Prostate
      Cancer and Prostatic Diseases (2001) 4, 167-172.

PMID- 12497037
TI  - Effects of bicalutamide and leuprolide on prostate-specific antigen (PSA), acid
      phosphatase (ACP) and prostatic acid phosphatase (PAP) in men with benign
      prostatic hyperplasia (BPH).
AB  - The effects of the nonsteroidal antiandrogen bicalutamide (Casodex(TM)) and the
      luteinizing hormone releasing hormone agonist leuprolide depot (Procren
      Depot(TM), Lupron Depot(TM)) on serum prostate-specific antigen (PSA), acid
      phosphatase (ACP), and prostatic acid phosphatase (PAP) in patients with benign
      prostatic hyperplasia (BPH) were determined. Thirty patients with BPH were
      randomised to receive bicalutamide 50 mg orally once daily or a placebo for 24
      weeks, followed by 24 weeks of follow-up (bicalutamide study). In another study
      55 men were randomised between 3.75 mg leuprolide depot intramuscularly at every
      28 days for 24 weeks or placebo injections (leuprolide study). In both studies
      blood sampling was performed at baseline, at week 12 at week 24 and 24 weeks
      after the end of therapy. Androgen suppression with bicalutamide 50 mg daily for
      24 weeks resulted in a median of 56% reduction of PSA (P<0.001 when compared to
      placebo). Acid phosphatase and PAP did not change. Leuprolide resulted in a
      median of 87% reduction of serum PSA (P<0.001) and a 39% reduction of PAP
      (P=0.023), whereas ACP was unchanged. Both bicalutamide and leuprolide induced a
      pronounced decline in serum PSA in BPH patients. The studies suggest a stronger
      androgen suppressive effect of leuprolide than of bicalutamide, but this
      difference might largely be due to too low a dosage of bicalutamide. ACP and PAP
      were relatively insensitive to androgen suppression. Our study suggests a
      different degree of androgen suppression on PSA originating from benign tissue
      versus cancer tissue, and that the direction of this discrepancy might be
      different for various androgen suppressive regimens.Prostate Cancer and Prostatic
      Diseases (2001) 4, 173-177.

PMID- 12497039
TI  - British Prostate Group Spring Meeting: 2nd and 3rd April 2001, The Western
      Conference Centre, Sackville Street, Manchester.

PMID- 12497038
TI  - Haematuria; a late complication of TURP?
AB  - This study was designed to investigate the cause of haematuria for patients that
      had previously undergone a TURP. One hundred patients were identified in a walk
      in haematuria clinic as having been treated by TURP and were prospectively
      investigated for the cause of bleeding. Prostate regrowth was the diagnosis in
      63% of cases. A diagnosis of malignancy was made for 23.5% of these patients. We
      have confirmed the hypothesis that for patients who present with haematuria after
      a TURP, the prostate is the usual source of bleeding.Prostate Cancer and
      Prostatic Diseases (2001) 4, 178-179.

PMID- 12497040
TI  - What's hot in the prostate?

PMID- 12497041
TI  - Editorial.

PMID- 12497042
TI  - Will the experience with tamoxifen in breast cancer help define the role of
      antiandrogens in prostate cancer?
AB  - Breast and prostate cancers are the two predominant hormone-responsive tumours.
      The use of the antioestrogen tamoxifen in the treatment of breast cancer has
      evolved over the past 30 y from treatment for advanced breast cancer to
      prevention. Tamoxifen is currently the endocrine treatment of choice for advanced
      breast cancer and for adjuvant therapy in a broad spectrum of women whose primary
      tumours have functional oestrogen receptors. It has also been shown to reduce the
      incidence of breast cancer in high-risk women. Non-steroidal antiandrogen therapy
      is used in the treatment of prostate cancer, but its role is still being defined.
      The clinical development of tamoxifen and that of the antiandrogens are reviewed
      and parallels are uncovered which provide insight into contemporary and future
      management of hormone-responsive prostate cancer.Prostate Cancer and Prostatic
      Diseases (2001) 4, 72-80

PMID- 12497043
TI  - Prostate cancer chemoprevention agents exhibit selective activity against early
      stage prostate cancer cells.
AB  - Preclinical models for the identification of prostate cancer chemoprevention
      agents are lacking. Based upon the notion that clinically useful chemoprevention
      agents should exhibit selective activity against early stage disease, studies
      were undertaken to assess whether chemoprevention agents selectively inhibited
      the growth of early stage prostate cancer, as compared to late stage cancer.
      First, a series of cell and molecular studies were performed, which, when taken
      together, validated the use of a panel of prostate cell lines as a model of the
      different stages of carcinogenesis. Next, therapeutic responsiveness to ten
      different cytotoxic or chemoprevention agents was evaluated. Chemoprevention
      agents exhibited selective activity against normal and early transformed prostate
      tissue, whereas cytotoxic agents were non-specific. Selective activity against
      early versus advanced prostate cancer cells is identified as a potential
      screening method for chemoprevention agents.Prostate Cancer and Prostatic
      Diseases (2001) 4, 81-91

PMID- 12497044
TI  - Detection of preneoplasia in histologically normal prostate biopsies.
AB  - P2X immunolabeling of prostate detected preneoplastic changes in apparently
      normal tissue. Labeling occurred in two well-defined stages before the diagnostic
      histological markers of cancer were visible. As cancer progressed, the location
      of P2X expression changed from confinement within individual nuclei in the acini
      (stage 1) to a cytoplasmic punctate label in the acinal epithelium, with an
      associated removal of nuclear stain (stage 2). Finally, in advanced cases, where
      clear morphological evidence of cancer was apparent, the P2X label condensed
      exclusively on the apical epithelium (stage 3). BPH/normal tissue was entirely
      devoid of P2X label. Biopsy samples (77) were tested in three categories. One
      group (35) were diagnosed as normal benign prostatic hyperplasia (BPH) on the
      basis of haematoxylin and eosin (H&E) stain, although underlying disease was
      suspected. Of these, 14 (40%) were clearly normal and appeared entirely devoid of
      label, 13 (37%) exhibited the first stage of P2X receptor labeling and the
      remaining eight (23%) exhibited second stage labeling. The accompanying H&E
      stained sections of all these cases had a normal appearance. Low grade cancer
      biopsy samples with Gleason scores G4-7 (25) all revealed widespread second stage
      receptor labeling in areas of both normal and cancerous morphology, while 17 high
      grade cancer biopsy samples (Gleason G8-10) all showed third stage labeling along
      with some residual second stage labeling. The features of each P2X labeling stage
      occupied the entire histological area affected, offering more opportunity to
      diagnose the tissue than was supplied by the more-localised diagnostic features
      identified by H&E-stain. Besides detecting cases of preneoplasia in biopsies with
      a normal H&E appearance, this technique was also able to rule out the presence of
      neoplasia in purely hyperplasic prostates by the absence of any P2X
      labeling.Prostate Cancer and Prostatic Diseases (2001) 4, 92-96

PMID- 12497045
TI  - An investigation into the spatial relationship between prostate intraepithelial
      neoplasia and cancer.
AB  - The distribution of high grade prostate intraepithelial neoplasia (PIN) and
      cancer was analysed in 18 separate areas from 89 radical prostatectomy specimens
      that had been sectioned and digitally imaged. When the occurrence of each type of
      pathology was summated a predilection was demonstrated for both pathologies in
      the apex of the prostate and a linear relationship was found between the
      frequency of cancer and high grade PIN (r(2)=0.744, P<0.05). This relationship
      was strongest at the apex (r(2)=0.621, P<0.005), lower in the midgland
      (r(2)=0.828, P<0.05) and bordered on significance at the base (r(2)=0.621,
      P<0.063). These results support the theory that cancer could obliterate high
      grade PIN as it over grows the areas once occupied by PIN.Prostate Cancer and
      Prostatic Diseases (2001) 4, 97-100

PMID- 12497046
TI  - A pilot study analyzing PSA, serum testosterone, lipid profile, body mass index
      and race in a small sample of patients with and without carcinoma of the
      prostate.
AB  - Androgens, diet, race and obesity are thought to play some roles in the
      pathogenesis of prostate cancer. We wanted to evaluate if there were any inter
      relationships between prostate specific antigen (PSA), serum testosterone, serum
      cholesterol, HDL, triglycerides, body mass index (BMI) and race, in older
      patients with and without prostate cancer (CaP). We evaluated 308 patients
      referred to urologists in private practice offices and clinics with and without
      prostate cancer with regard to race, serum PSA, age, serum testosterone, full
      lipid profile, height and weight, and stage of cancer. We used multivariate
      analysis, Fisher's exact test and t-tests as well as logistic regression
      analysis. Data was analyzed using SPSS computer software, and P-values<0.05 were
      considered statistically significant. Significantly higher levels of serum
      testosterone were found in black men with CaP than black men without CaP (526+/
      28 vs 404+/-19, respectively.) We also found significantly higher levels of serum
      testosterone in white men with CaP than white men without CaP (409+/-20 vs 302+/
      14, respectively, P<0.05). HDL was higher in black men than white men, and
      triglycerides were higher in white men than black men. Cholesterol was similar
      across all groups, but BMI was highest in white men with CaP. We also found a
      significant association between BMI and pathological stage of prostate cancer
      patients among both black and white men (P<0.05). Our study demonstrated that
      black men who developed CaP had higher serum testosterone levels, on average,
      than white men who developed CaP. Furthermore, BMI was highest in white men
      developing CaP compared to black men, but we found a significant association
      between pathological stage and BMI in both black and white patients. Although it
      is controversial whether obesity is considered to be a risk factor for prostate
      cancer, this small pilot study suggests that BMI may play a role in the
      progression of the disease once it is established.Prostate Cancer and Prostatic
      Diseases (2001) 4, 101-105

PMID- 12497047
TI  - Differential expression of angiogenic cytokines by cell lines and primary
      cultures of human prostate cancer.
AB  - Studies on angiogenic cytokines usually are initially based upon their expression
      by available established cell lines. Our hypothesis is that established
      epithelial prostate cancer (CaP) cell lines do not accurately reflect angiogenic
      cytokine expression as compared to epithelial and stromal components of primary
      cultures generated from clinical CaP specimens. Serum free and growth factor free
      conditioned medium (CM) was collected from PC3, LNCaP, and their orthotopic
      selected prostate cancer sublines. Surgically acquired and pathologically
      confirmed neoplastic prostate tissue was selectively grown for selection of
      epithelial or stromal components, and CM was also collected. CM was assayed for
      urokinase (u-PA), basic fibroblast growth factor (bFGF), vascular endothelial
      growth factor (VEGF), and tumor necrosis factor alpha (TNF-alpha). u-PA was
      expressed only by androgen independent cell lines, but was detectable in the
      epithelial and stromal cultures of androgen sensitive primary cultures. bFGF was
      not secreted by cell lines nor epithelial primary cultures. VEGF was universally
      expressed, but TNF-alpha was not secreted by cells lines nor primary cultures.
      These data suggest that the expression of angiogenic cytokines by established
      epithelial CaP cell lines does not reflect epithelial and stromal primary
      cultures.Prostate Cancer and Prostatic Diseases (2001) 4, 106-111

PMID- 12497048
TI  - Safety and efficacy of a non-steroidal anti-androgen, based on results of a post
      marketing surveillance of nilutamide.
AB  - The use, tolerability and efficacy of the non-steroidal anti-androgen nilutamide
      (Anandron(R)) in daily clinical practice was investigated in this 5-y project. In
      total 725 patients were recruited from 27 Dutch centres. The investigated
      population was very heterogeneous and different therapeutic options were
      reported. We may conclude that in general good results have been obtained,
      especially in first line combination therapy combined with luteinising hormone
      releasing hormone (LHRH) agonists. Patients with a good performance status at
      inclusion seem to benefit more from nilutamide combination therapy.Prostate
      Cancer and Prostatic Diseases (2001) 4, 112-117

PMID- 12497049
TI  - A population-based study on radical prostatectomy in France.
AB  - There has as yet been no descriptive study of the practice of radical
      prostatectomy in the general population in France. The objective of this work was
      to investigate the use of radical prostatectomy (RP) in France and its
      determinants and geographic variations. A total of 175 radical prostatectomies
      was identified in a random sample of 798 cases of prostate cancer recorded in
      1995 by four cancer registries, in the departments of Bas-Rhin, Calvados, Isere
      and Tarn. Tumour characteristics, diagnostic procedures and histopathological
      results were analysed. Multivariate analysis by logistic regression was used to
      take into account age, prostate specific antigen (PSA) levels and clinical stage
      in order to study variations between geographical departments and sectors of
      activity (private or public). The mean age of the patients at the time of
      diagnosis was 65.3 y (range 46-76). Median PSA level was 18.2 ng/ml (range 1
      184). Diagnosis was made by randomised biopsies in 73.8% of cases or by
      transurethral resection (6.9%). Clinical stage was classified T(1) (22.3%), T(2)
      (64%), T(3) (8.6%), N(+) (0.6%) and unknown (4.5%). The histopathological result
      was pT(2)N0 in 46.3% of cases, pT(3)N0 in 40%, pT(4)N0 in 1.7%, pT(x)N(+) in 8.6%
      and unknown in 3.4%. Adjuvant therapy (radiotherapy 13.7%, hormonal treatment
      13.7% or both 3%) was administered in 54 patients (31%). Logistic regression
      showed that the probability of undergoing RP was three times higher in one
      department than in the other departments, and was 2.6 times as high in the
      private sector. This study on the practice of RP is the first performed in the
      general population in France. It shows that practice differs according to
      geographical region and sector of activity, indicating that schools of thought
      and medical culture vary within the same country.Prostate Cnacer and Prostatic
      diseases (2001) 4, 118-123

PMID- 12497050
TI  - Treatment of lower urinary tract symptoms suggestive of benign prostatic
      obstruction in real life practice in France.
AB  - The objective of this work is to describe the profile of prevalent and incident
      populations suffering from lower urinary tract symptoms (LUTS) suggestive of
      benign prostatic obstruction (BPO) and to analyse the management of care by 620
      general practitioners (GPs) in France in 1997 and 1998. Patient records were
      extracted from the THALES database. Special attention was given to the use of
      medical therapy and switch rates (ie change to another or combination with
      another drug). In real life practice (RLP) French GPs predominantly utilise
      alpha(1)-adrenoceptor antagonists for the treatment of LUTS. This is in agreement
      with available evidence from randomised controlled trials (RCTs) with different
      medical therapies (alpha(1)-adrenoceptor antagonists, finasteride, plant
      extracts). On the contrary, the relatively high usage of phytotherapy might be
      explained by traditional and personal preferences. Using purely descriptive
      statistics, newer alpha(1)-adrenoceptor antagonists, alfuzosin and tamsulosin,
      seem to be the most frequently prescribed medical therapy for new patients and
      are, moreover, associated with a low switch rate.Prostate Cancer and Prostatic
      Diseases (2001) 4, 124-131

PMID- 12497051
TI  - Introduction.

PMID- 12497052
TI  - The Relationship between LUTS and sexual function.
AB  - Lower urinary tract symptoms (LUTS) are common in middle-aged and elderly men and
      are frequently caused by an enlarged prostate. Increasing severity of LUTS may
      negatively affect patients' health-related quality of life (QoL) to varying
      degrees. Sexual function is an important aspect of QoL and studies show that
      sexual dissatisfaction increases with increased severity of LUTS. The ICS-BPH
      International Study of 1271 men aged 45 y and over who reported to one of 12
      clinics examined the relationship between urodynamic parameters, LUTS, sexual
      dysfunction and QoL. Results showed that nearly 90% of men found that the effect
      of LUTS on their sex lives was a problem and 45% reported that their sex lives
      were spoilt by LUTS. Storage symptoms, in particular incontinence, had a greater
      association with sexual dysfunction than voiding symptoms. Similar results were
      reported in the ICS-BPH UK Community Study, which involved 423 men aged 40 y and
      over. In contrast, a French Community Study of 2011 men aged 50-80 y reported
      that symptoms of hesitancy, straining, reduced stream and wet underclothes were
      most strongly associated with sexual dysfunction. Sexuality is clearly of concern
      to men with LUTS and should be included in discussions on treatment
      decisions.Prostate Cancer and Prostatic Diseases (2001) 4, S2-S6

PMID- 12497053
TI  - Assessment of male sexual function.
AB  - Sexuality is a complex entity involving several aspects, including desire,
      libido, pleasure, sexual life, intercourse, erection, ejaculation, orgasm,
      happiness and bother. Sexuality can be assessed through patient-doctor interviews
      as well as through self-completing questionnaires. A number of these have been
      validated and translated into several languages. It is important that such
      questionnaires are simple and easy for the patient to complete. One commonly used
      instrument is the International Index of Erectile Function (IIEF), which involves
      15 questions on five domains: erectile function, orgasmic function, sexual
      desire, intercourse satisfaction and overall satisfaction. This has recently been
      simplified to five questions (IIEF-5). A number of questionnaires, such as the
      modified Danish Prostatic Symptom Score (DAN-PSS) and International Continence
      Society sex (ICSsex), take into account the bother caused by sexual dysfunction.
      There is expected to be an increasing number of sexually active men consulting
      with lower urinary tract symptoms (LUTS) as the population ages. Evidence
      suggests that the severity of LUTS is linked with sexual dysfunction and
      consequently this significant aspect of life for men of all ages should be taken
      into consideration in the management of LUTS associated with benign prostatic
      hyperplasia (BPH).Prostate Cancer and Prostatic Diseases (2001) 4, S7-S11

PMID- 12497054
TI  - Impact of treatment of BPH on sexuality.
AB  - Benign prostatic hyperplasia (BPH) can have a profound affect on a patient's
      quality of life and sexual function and is considered by patients to be one of
      the most important aspects affected by the disease. Different treatments can
      produce a variable response in terms of the patient's quality of life, including
      sexual activity and satisfaction. Varying rates of erectile dysfunction (ED) and
      retrograde ejaculation following surgery for BPH have been reported. In general,
      the incidence of these side-effects is less after minimally invasive therapies,
      such as interstitial laser coagulation and transurethral microwave therapy, but
      the data available are limited. The lowest rates of sexual dysfunction are
      reported with medical therapies. The 5alpha-reductase inhibitor, finasteride, can
      result in ED in 5-9% of patients and ejaculation disorders in 0.8-2.0%. With the
      exception of tamsulosin, alpha(1) blockers are associated with a low rate of
      sexual dysfunction. No cases of ED have been reported with alfuzosin and abnormal
      ejaculation with terazosin or alfuzosin is negligible. Indeed, early research
      suggests a beneficial effect of alpha(1) blockers on sexual function. In addition
      to information on the efficacy of a particular therapy, patients should be
      informed of side effects, in particular those relating to sexual function, in
      order that they can make informed treatment decisions.Prostate Cancer and
      Prostatic Diseases (2001) 4, S12-S16

PMID- 12497055
TI  - What's hot in the prostate?

PMID- 12497056
TI  - Editorial.

PMID- 12497057
TI  - Treatment of clinically localized prostatic carcinoma: helping our patients make
      an informed decision.

PMID- 12497058
TI  - BAUS Section of Oncology and The British Prostate Group Joint Meeting.

PMID- 12497059
TI  - Local therapy for prostate-specific antigen recurrence after definitive
      treatment.
AB  - Disease recurrence after local therapy for prostate cancer is increasingly
      common, most often with detectable or rising prostate-specific antigen (PSA) the
      earliest sign. Analysis of clinical and pathological factors can help determine
      which patients are at risk for treatment failure, while PSA characteristics and
      imaging studies can localize site of recurrent disease and identify men who may
      benefit from salvage therapy. Local treatment options include radiation therapy
      (external beam and brachytherapy) and cryoablation for patients who have
      undergone prostatectomy, and surgery, brachytherapy, and cryoablation for
      patients who have received radiotherapy. Novel treatment modalities are under
      investigation and may improve success of local salvage therapy while minimizing
      morbidity. Prostate Cancer and Prostatic Diseases (2001) 4, 20-27

PMID- 12497060
TI  - Defining a role for the inhibitors of apoptosis proteins in prostate cancer.
AB  - The aim of this paper is to review the inhibitors of apoptosis proteins, a
      recently discovered group of caspase inhibitors. We will briefly review the
      relevance of apoptosis in prostate cancer and some of the control mechanisms,
      before describing the structure, function and regulation of these molecules.
      Lastly, we will consider the evidence for the role that IAPs may have in cancer
      and the implications for prostate cancer in particular. Prostate Cancer and
      Prostatic Diseases (2001) 4, 28-32

PMID- 12497061
TI  - Farnesyl:protein transferase inhibitors as potential agents for the management of
      human prostate cancer.
AB  - The effects of farnesyl:protein transferase inhibitors (FTIs) were evaluated
      against hormone-dependent and hormone-independent prostate cancer cell lines
      harboring mutant and wild type Ras. The combinations of the FTI with hormones and
      chemotherapy were explored. The effect of FTI on the growth of human prostate
      cancer lines was examined under anchorage-dependent and -independent conditions.
      Changes in Ras processing and cellular localization were examined by
      immunoblotting and immunocytochemistry. Hormone-dependent (LNCaP) and 
      independent (TSU-Pr1, PC3 and DU145) human prostate cancer cell lines were growth
      inhibited by the FTI L-744,832 at concentrations ranging from 100 nM to 20
      &mgr;M. The inhibition was accompanied by loss of protein farnesylation and with
      the accumulation of Ha-Ras as its unprocessed, cytosolic form. No effect on N-
      and Ki-Ras processing was observed. The transformed phenotype of TSU-Pr1 cells,
      which possess a Ha-Ras Gly-12-Val activating mutation, reverted following FTI
      treatment. Enhanced antitumor effects were observed when the FTI was combined
      with gamma-radiation, etoposide, doxorubicin, cisplatin, estramustine and the
      antihormone bicalutamide. In particular, the combination of taxol and FTI was
      synergistic for DU145 cells, a cell line that is only marginally sensitive to the
      FTI alone. The sensitivity of human prostate cancer cell lines to the FTI is
      independent of the presence of mutations of tumor suppressors, cell cycle
      regulators and of the activation of a variety of oncogenes, including Ras. A cell
      line expressing mutated Ha-Ras is particularly sensitive. Enhanced antitumor
      effects were observed with an anti-androgen, gamma-irradiation, and several
      chemotherapeutic agents. These findings support the clinical evaluation of FTIs
      alone or in combination as treatment for this disease. Prostate Cancer and
      Prostatic Diseases (2001) 4, 33-43

PMID- 12497062
TI  - Combination gene therapy with adenoviral vector-mediated HSV-tk+GCV and IL-12 in
      an orthotopic mouse model for prostate cancer.
AB  - We previously demonstrated significant therapeutic activities associated with
      adenoviral vector-mediated Herpes Simplex Virus/thymidine kinase (AdHSV-tk) with
      ganciclovir (GCV) in situ gene therapy in the RM-1 orthotopic mouse prostate
      cancer model and interleukin-12 (AdmIL-12) in situ gene therapy in the RM-9
      orthotopic mouse prostate model for prostate cancer. In both protocols, local
      cytotoxicity and activities against pre-established lung metastases were
      demonstrated. To test whether combined AdHSV-tk+GCV+IL-12 gene therapy would lead
      to enhanced therapeutic effects when compared to either treatment alone, we used
      RM-9 mouse prostate cancer cells in both orthotopic and pre-established lung
      metastases models of prostate cancer. Combined treatment with a single injection
      of optimal doses of AdHSV-tk+GCV or AdmIL-12 led to significantly increased
      suppression of orthotopic tumor growth. IL-12 gene therapy alone was more
      effective than AdHSV-tk+GCV in suppressing spontaneous lymph node metastases and
      pre-established lung metastases but combination gene therapy did not result in
      additional anti-metastatic activities. Combination gene therapy also did not
      achieve significantly better animal survival compared to AdHSV-tk+GCV or AdmIL-12
      alone. Analysis of localized antitumor activities demonstrated that AdHSV-tk+GCV
      therapy induced higher levels of necrosis compared to AdmIL-12 or combination
      therapy. However, both treatments alone and combination therapy produced similar
      increases in apoptotic index. To address the possible mechanisms of locally co
      operative cytotoxic activities, we analyzed the systemic natural killer (NK)
      response and the numbers of tumor-infiltrating immune cells using quantitative
      immunohistochemical analysis. AdHSV-tk+GCV therapy alone led to detectable
      increases in iNOS-positive cells, CD4+and CD8+T-cells and moderately increased
      numbers of F4/80 (macrophage selective)-positive cells within treated tumors. In
      contrast, AdmIL-12 elicited a highly robust pattern of tumor infiltration for all
      four of these immune cells that was in general mimicked by combination therapy.
      Further analysis of the accumulation of transforming growth factor-beta1 (TGF
      beta1) immunohistochemical staining demonstrated that AdHSV-tk+GCV treatment, but
      not AdmIL-12 treatment, produced cancer cell-associated increases in this
      cytokine relative to control Ad-beta-gal injections. Interestingly, local
      injection with AdHSV-tk+GCV induced significant splenocyte-derived NK cell
      cytolytic activities with maximal response 7 days following treatment, whereas
      AdmIL-12 injection produced significantly higher NK activity with maximal
      response 2 days following injection. The combined treatment produced a higher
      systemic NK response over the 14-day treatment period. Depletion of NK cells in
      vivo demonstrated that this immunocyte subpopulation was responsible for early
      locally cytotoxic activities induced by AdHSV-tk+GCV but not AdmIL-12 and that NK
      activities were largely responsible for activities against pre-established
      metastases generated by both gene therapy protocols. Prostate Cancer and
      Prostatic Diseases (2001) 4, 44-55

PMID- 12497063
TI  - Correlation of transrectal ultrasound, computer analysis of transrectal
      ultrasound and histopathology of radical prostatectomy specimen.
AB  - A system for computerised analysis of ultrasonographic prostate images
      (AUDEX=Automated Urologic Diagnostic EXpert system) for the detection of prostate
      carcinoma was developed. The ultimate goal is to develop a system that is
      reliable and non-observer dependent. Results of an earlier study with a small
      group were encouraging and this study describes the results of the computerised
      analysis in a larger group. Sixty-two patients who were scheduled to undergo a
      radical prostatectomy were prospectively analysed. The radical prostatectomy
      specimens were step-sectioned in the transverse plane, corresponding to the
      ultrasound pictures. Malignant regions identified by each study were quantified
      and compared by computer calculation. No correlation was observed between
      ultrasound analysis and pathology result. For the AUDEX analysis an overall
      sensitivity of 85% and a specificity of 18% with only a diagnostic accuracy of
      57% was noticed when presence or absence of malignancy was evaluated by octant
      (total 496). When applying a cut-off value of 0.5 ml the numbers were 71%, 33%
      and 55%, respectively. Correlation was significantly better for the ventral
      octants. In this study the earlier results of our AUDEX system could not be
      confirmed. Although sensitivity was good, specificity and especially diagnostic
      accuracy were lower than expected. We have to conclude that the current settings
      are inappropriate for routine clinical use. Prostate Cancer and Prostatic
      Diseases (2001) 4, 56-62

PMID- 12497064
TI  - The critical role of patient follow-up after receiving a diagnosis of prostatic
      intraepithelial neoplasia.
AB  - With the increasing incidence of prostatic intraepithelial neoplasia being found
      at the time of prostate biopsy and the association of prostatic intraepithelial
      neoplasia to coexisting prostate cancer and/or the future development of prostate
      cancer, patient compliance in following post-biopsy follow-up instructions for re
      biopsy is becoming more significant in the detection of prostate cancer at an
      earlier and, therefore, potentially curable stage. During a 3-y period, we
      reviewed the charts of 130 patients who received an initial diagnosis of
      prostatic intraepithelial neoplasia after undergoing transrectal ultrasound of
      the prostate with biopsy. It is our policy to inform the patient of their
      diagnosis of prostatic intraepithelial neoplasia at the time of the initial
      biopsy and to recommend a repeat biopsy in 6-12 months. Patients are informed of
      the diagnosis of prostatic intraepithelial neoplasia verbally and in writing. In
      addition, a letter is sent to their referring physician with the re-biopsy
      recommendation. Thirty-nine of 130 patients (30%) were seen for re-biopsy within
      the specified time. An additional 36 patients (27.69%) were re-biopsied between
      12 and 18 months after the initial diagnosis of prostatic intraepithelial
      neoplasia. An additional 11 patients (7%) were re-biopsied more than 18 months
      after their initial diagnosis. Forty-four patients failed to return for re
      biopsy. Overall, patient follow-up within the desired protocol was poor and must
      be improved upon to prevent any delays in the diagnosis of prostate cancer.
      Prostate Cancer and Prostatic Diseases (2001) 4, 63-66

PMID- 12497065
TI  - What's hot on the prostate?

PMID- 12497066
TI  - Editorial.

PMID- 12497067
TI  - Prostate cancer 2000.

PMID- 12497068
TI  - Androgens and growth factors in prostate cancer: a transgenic perspective.
AB  - With the advent of transgenic technology, novel animal models are being developed
      to facilitate prostate cancer research. The ability to perform genetic
      perturbation studies in a temporally and spatially restricted manner has
      established a new paradigm for investigations of the molecular mechanisms
      involved in the initiation, progression and metastogenesis of prostate cancer.
      Using the transgenic adenocarcinoma of the mouse prostate (TRAMP) model we have
      begun to identify specific molecular events related to the emergence of the
      androgen-insensitive phenotype. In addition, a number of new models have recently
      been generated to characterize how the deregulation of stromal to epithelial
      interactions mediated by polypeptide growth factor signaling could facilitate
      transformation of the prostate. It is anticipated that these models and their
      successors will ultimately provide new molecular pathway-based strategies for the
      prevention, detection and treatment of prostate cancer. Prostate Cancer and
      Prostatic Diseases (2000) 3, 224-228

PMID- 12497069
TI  - In vitro human cell culture models for the study of prostate cancer.
AB  - Prostate cancer is the most commonly diagnosed malignancy in the American men and
      the second leading cause of male cancer death in the United States. Despite its
      high incidence, the molecular and genetic events involved in prostate cancer
      progression remain poorly understood. A hurdle in understanding the molecular
      genetic changes in prostate cancer has been the difficulty in establishing
      premalignant lesions and primary prostate tumors as in vitro cell cultures.
      Primary epithelial cells grow for a finite life span and then senesce.
      Immortalization is defined by continuous growth of otherwise senescing cells and
      is believed to represent an early stage in tumor progression. In order to examine
      these early stages, we and others have developed in vitro models of prostate
      epithelial cell immortalization. Because prostate cancer is a multistep,
      progressive disease with a typical onset later in life and with an unusually high
      number of latent cases that do not develop into clinically manifest cancer, the
      steps in the progression to malignancy are of particular interest. To understand
      the many factors that are suspected to contribute to the development of this
      malignancy, there is a need for an in vitro multistep human prostate epithelial
      (HPE) culture system. These models have been extremely important in identifying
      genetic and molecular changes involved in prostate cancer progression. Prostate
      Cancer and Prostatic Diseases (2000) 3, 229-235

PMID- 12497070
TI  - The role of candidate genetic polymorphisms in the etiology of prostate cancer.
AB  - Prostate cancer appears to result from complex interactions among genetic,
      endocrine and environmental factors. Identification of risk factors for
      development and progression of prostate cancer is needed. This will allow
      researchers to design strategies to reduce the morbidity and mortality from this
      cancer and to identify individuals at increased risk of developing the disease.
      It is probable that common genetic polymorphisms (variants) in genes directly and
      indirectly involved in androgen biosynthesis, metabolism and regulation are
      important. Other important genes are likely to be those directly involved in
      regulation of prostate cell proliferation and apoptosis.Prostate Cancer and
      Prostatic Diseases (2000) 3, 236-240

PMID- 12497071
TI  - High risk genes predisposing to prostate cancer development-do they exist?
AB  - There is evidence for genetic predisposition to prostate cancer. However,
      prostate cancer genes have been more difficult to find than genes for some of the
      other common cancers, such as breast and colon cancer. The reasons for this are
      discussed in this article and it is now becoming clear that prostate cancer is
      probably due to multiple genes, many of which are moderate or low penetrance. The
      advances in the Human Genome Project and technology, especially that of robotics,
      will help to overcome these problems. Prostate Cancer and Prostatic Diseases
      (2000) 3, 241-247

PMID- 12497072
TI  - Targeted screening for prostate cancer in African-American men.
AB  - African-American men and black men throughout the world have a higher rate of
      prostate cancer than other ethnic groups. They also are most likely to present at
      a younger age with more advanced disease and have historically had a poorer
      prognosis. Whether this observed difference is due to behavior, lack of access,
      environmental factors or genetics is hotly debated. Whatever the cause or causes,
      there is growing concensus that targeting screening to this high-risk group is
      justified. Focused education about risk and screening in black men can be
      effective and demonstration screening programs in African-American community
      settings have been successful. There is much debate about the proper normal
      values of PSA to be used in screening high risk black men. Some have argued for a
      very low normal range such as </=2.0 ng/ml to improve sensitivity for detection
      of curable disease. Others, recognizing the balance between sensitivity (cancer
      detection) and specificity (avoiding unnecessary prostate biopsies), have
      proposed age-adjusted PSA ranges. Until randomized or prospective screening
      trials are completed, it seems reasonable to encourage black men to start
      screening at age 40 using a PSA threshold of </=2.0 to 2.5 ng/ml to prompt
      further evaluation. Prostate Cancer and Prostatic Diseases (2000) 3, 248-255

PMID- 12497073
TI  - The influence of dietary and environmental factors on prostate cancer risk.
AB  - Prostate cancer is the most common malignancy found in males and one of the most
      common causes of cancer death. The epidemiology implicates environmental and
      nutritional factors in the initiation and progression of the disease.
      Identification of these factors would allow chemoprevention strategies to be
      tested. Potent mutagenic and carcinogenic heterocyclic amines and polycyclic
      aromatic hydrocarbons are produced in cooked meat, and following metabolic
      activation some of them are strongly associated with prostate carcinogenesis in
      rodents. Primary cell cultures of human prostate epithelial cells were obtained
      from patients undergoing transurethral resection of the prostate. Metabolic
      activation of the cooked food carcinogens 2-amino-1-methyl-6-phenylimidazo- [4,5
      b]pyridine (PhIP) and benzo[a]pyrene (B[a]P) was examined and resultant DNA
      damage (single strand breaks) measured using the Comet assay. Increased
      concentrations of carcinogen were associated with increased DNA damage and comet
      tail length compared to controls. Prostate Cancer and Prostatic Diseases (2000)
      3, 256-258

PMID- 12497074
TI  - Investigating the clinical utility of the percent of positive prostate biopsies
      in predicting PSA outcome following local therapy for patients with clinically
      localized prostate cancer.
AB  - The clinical utility of the percent of positive prostate biopsies in predicting
      prostate-specific antigen (PSA) outcome following radical prostatectomy (RP), or
      external beam radiation therapy (RT), for men with PSA detected, or clinically
      palpable prostate cancer was investigated. After accounting for the established
      prognostic significance of the PSA level, biopsy Gleason score and the clinical T
      stage, the percent of positive prostate biopsies added clinically significant
      information regarding time to PSA failure following RP. These findings were
      validated in the intermediate risk patients using an independent surgical and
      radiation data set. Prostate Cancer and Prostatic Diseases (2000) 3, 259-264

PMID- 12497075
TI  - Prognostic and treatment-predictive factors-is there a difference?
AB  - The terms risk factor, prognostic factor and predictive factor are often
      imprecisely used. We defined a prognostic factor as a patient characteristic that
      identifies subgroups of untreated patients having different outcomes, and a
      factor predictive of treatment effect as a patient characteristic that identifies
      subgroups of treated patients having different (as a consequence of treatment)
      outcomes. To illustrate this, theoretical graphical examples were constructed and
      data from the literature on prostate cancer were used to substantiate the
      theoretical examples. In most situations, but not necessarily always, a
      prognostic factor is also pre- dictive of the effect of specific treatments.
      Whether a prognostic factor is also predictive of treatment effect or not can
      only be assessed in a valid comparative setting such as in a randomized trial. A
      factor that is predictive for treatment effect may not be predictive for another
      treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 265-268

PMID- 12497076
TI  - Use of pretreatment prostate-specific antigen doubling time to predict outcome
      after radical prostatectomy.
AB  - The objective of this study was to better understand the implications of the rate
      of prostate-specific antigen (PSA) changes in prostate carcinoma. We
      retrospectively calculated PSA doubling times prior to surgery in 62 patients
      with prostate carcinoma. The calculated values were compared with final
      pathologic findings and with rates of PSA failure after surgery. PSA values
      increased during the period of observation in 82.3% of the patients, whereas
      17.7% had levels that remained stable. The median calculated PSA doubling time in
      those with increasing levels was 25.8 months, with doubling times </=24 months
      observed in 37.1% of the patients. Stage pT3 disease was more common in patients
      with PSA doubling times of </=36 months than in those with doubling times >36
      months (P=0.02). Biochemical failure was more common in patients with rapid PSA
      doubling times (P<0.01). The calculated PSA doubling time prior to radical
      surgery is significantly associated with the final pathologic findings. Early PSA
      failure is more common in patients with rapid PSA doubling times prior to radical
      surgery. Prostate Cancer and Prostatic Diseases (2000) 3, 269-274

PMID- 12497077
TI  - Polyamine depletion therapy in prostate cancer.
AB  - The prostate gland has among the highest level of polyamines in the body and
      prostate carcinomas have even greater elevated polyamine levels. These ubiquitous
      molecules synthesized by prostate epithelium are involved in many biochemical
      processes including cellular proliferation, cell cycle regulation, and protein
      synthesis. These properties have made polyamines a potential target for
      therapeutic intervention in diseases of excessive cell proliferation such as
      cancer. However, attempts to limit tumor growth by inhibition of polyamine
      synthesis have not been very successful since cells have the capacity to take up
      polyamines from the bloodstream. We report here studies utilizing polyamine
      depletion by means of a combination of blockade of polyamine synthesis with DFMO
      (alpha-difluoromethylornithine), an inhibitor of ornithine decarboxylase, the
      rate limiting enzyme in the polyamine synthetic pathway, and ORI 1202, a novel
      inhibitor of polyamine transport into the cell. This cytostatic combination, even
      in the presence of excess extracellular polyamines, significantly slowed the
      growth of the human tumor cell line PC-3 grown in tissue culture with an EC(50)
      in the &mgr;M range. Other prostate cell lines were similarly growth inhibited
      including LNCaP.FGC and DU145. Growth of the PC-3 tumor cell line as a xenograft
      in nude mice was also slowed significantly by this combination of compounds.
      Polyamine levels in the tumor were lowered from control tumor levels. This
      combination therapy could provide an effective and potentially non-toxic therapy
      for prostate tumors.Prostate Cancer and Prostatic Diseases (2000) 3, 275-279

PMID- 12497078
TI  - Intermittent androgen deprivation therapy: schedule modifications based on a
      novel in vivo human xenograft model.
AB  - In most clinical trials of intermittent androgen deprivation (IAD), the decision
      to stop androgen withdrawal is based on monitoring PSA levels, waiting for its
      drop to nadir. Based on in vitro pre-clinical studies, a modified 'on-off'
      schedule of short intervals of androgen deprivation, designated pulsed androgen
      deprivation (PAD), is proposed to destroy androgen dependent (AD) cells more
      gradually and to conserve their androgen-independent (AI) inhibitory potential
      for longer periods, resulting in an overall prolongation of time to hormone
      resistant progression.Prostate Cancer and Prostatic Diseases (2000) 3, 280-282

PMID- 12497079
TI  - Bone morphogenetic protein-6: potential mediator of osteoblastic metastases in
      prostate cancer.
AB  - The mechanisms by which prostate cancer metastasizes to bone with a strong
      osteoblastic reaction remain poorly understood. Several factors have been
      previously implicated, including transforming growth factor-beta, fibroblast
      growth factors, endothelin-1 and bone morphogenetic proteins (BMPs). BMP-6
      expression has been shown exclusively in the malignant epithelial cells of
      prostate cancers that have metastasized, but not in organ confined disease.
      Expression of BMP-6 in radical prostatectomy specimens has been shown to
      correlate with increased recurrence rates and decreased survival. This article
      presents the results of work by the authors' group in this field and a current
      literature review. Prostate Cancer and Prostatic Diseases (2000) 3, 283-285

PMID- 12497080
TI  - Potential of intermittent hormone therapy for M+ and M0 prostate cancer patients.
AB  - Increasingly animal and clinical studies suggest that intermittent therapy may
      improve the duration of hormone dependence in patients with prostate cancer.
      However there remains uncertainty as to optimal duration of treatment and level
      of prostate-specific antigen (PSA) before treatment is restarted. The aim of this
      study was to identify risk factors that predict duration of therapy in prostate
      cancer patients receiving intermittent hormone therapy. Any patients who had
      achieved PSA complete remission after hormone therapy for metastatic or locally
      advanced prostate cancer were included in the study. Fifty patients entered on
      intermittent hormone therapy after achieving a PSA complete remission. In all,
      57% of patients remained off treatment at 12 months and the median time for
      restarting further hormone therapy was 14 months. At 1 y, 95% of patients
      retreated are progression free and overall 92% are alive at 3 y. There was some
      evidence that there was a slower progression to require treatment in older M0
      patients and those who had been on treatment for more than 9 months. Although M0
      patients receiving radiation concurrently after initial hormone down staging had
      a slower recurrence rate, 53% of M0 patients treated with hormone alone remained
      off hormones for more than one year. Clearly selection cannot be excluded as a
      cause for this good survival. However as overall survival in this study is at
      least as good as that of patients with M0 disease on hormone therapy in the
      immediate arm of the MRC immediate vs deferred therapy study, there is a case to
      extend examination of this approach to a randomized trial. This might also
      include patients failing to achieve PSA complete remission in order to examine
      the issue of whether continued androgen withdrawal is required in the terminal
      treatment phase of hormone-resistant patients to keep the hormone sensitive clone
      under control. Prostate Cancer and Prostatic Diseases (2000) 3, 286-289

PMID- 12497081
TI  - New strategies for the treatment of hormone-independent prostate cancer.
AB  - It is quite likely that in every prostate cancer, at the start of clinical
      disease there are hormone-independent cells present. These cells may be sensitive
      to changes in the diet, to chemotherapeutic agents, to immunological agents, to
      the use of vaccines or may be sensitive to radiotherapy. The introduction of
      these non-hormonal therapies has classically been reserved for the time when the
      patient has exhausted all other treatment therapies and has a large tumour volume
      which will almost certainly not respond to such treatments. The purpose of this
      chapter will be to try to arrive at a more sensible definition of hormone
      independent disease than has been used in the past, to outline some of the new
      treatment strategies and to make suggestions as to where in the natural history
      of the disease these would be most effectively and easily employed.Prostate
      Cancer and Prostatic Diseases (2000) 3, 290-295

PMID- 12497082
TI  - Anti-EGF receptor therapy.
AB  - The epidermal growth factor receptor (EGFR) signalling pathway contributes to a
      number of processes important to tumour progression, including cell
      proliferation, apoptosis, angiogenesis and metastatic spread. EGFR signalling is
      thought to be an important cell survival mechanism in hormone-resistant prostate
      cancer. ZD1839 ('Iressa') is an orally active, selective EGFR-tyrosine kinase
      inhibitor (EGFR-TKI) which blocks signal transduction pathways implicated in
      promoting cancer growth. In preclinical studies, ZD1839 alone, and in combination
      with cytotoxic agents, produced reversible growth inhibition and growth delay in
      a wide range of tumour cell lines and human tumour xenografts. Preliminary
      results from phase I trials in patients with advanced disease suggest that ZD1839
      has an acceptable tolerability profile and promising clinical efficacy in
      patients with a variety of tumour types, including hormone-resistant prostate
      cancer, where new treatment strategies are needed. Prostate Cancer and Prostatic
      Diseases (2000) 3, 296-302

PMID- 12497083
TI  - The immunotherapy of prostate cancer.
AB  - Advanced prostate cancer remains incurable with standard treatment options.
      Immunotherapy may be a realistic alternative given the growing evidence that the
      immune response can affect the growth of other solid tumours and the regulation
      of both specific and shared prostate cancer antigens. Early studies suggest that
      both non-specific and specific vaccines can effect relevant animal models and
      clinical trials based on these observations are now in progress. A number of
      other approaches including gene therapy with HSVtk are already undergoing
      clinical studies (Herman et al. Hum Gene Ther 1999; 10: 1239-1249). Prostate
      Cancer and Prostatic Diseases (2000) 3, 303-307

PMID- 12497086
TI  - Keyword Index To Volume 3.

PMID- 12497084
TI  - Targeting of adenoviral vectors for gene therapy of prostate cancer.
AB  - The transduction of cytotoxic genes by adenoviral vectors into prostatic cells
      offers a new entity for the treatment of prostate cancer. Current adenoviral
      vectors cannot infect prostatic cells selectively, and expression of therapeutic
      genes is often too low to be efficient. Bispecific antibodies may alter the
      natural tropism of adenoviral vectors towards prostatic cells, and increase the
      efficacy of infection (transductional targeting). The transcription of transgenes
      can be placed under the control of prostate-specific promoters (transcriptional
      targeting), and the combination of this with transductional targeting may be
      warranted to construct targeted vectors that are adequate for gene therapy of the
      prostate. Prostate Cancer and Prostatic Diseases (2000) 3, 308-312

PMID- 12497087
TI  - What's hot in the prostate?

PMID- 12497088
TI  - Editorial.

PMID- 12497089
TI  - Neoadjuvant hormonal therapy prior to radical prostatectomy: promises and
      pitfalls.
AB  - Prostate Cancer and Prostatic Diseases (2000) 3, 136-144

PMID- 12497090
TI  - SELECT: the Selenium and Vitamin E Cancer Prevention Trial: rationale and design.
AB  - Prostate cancer is the commonest non-skin malignancy in the United States and has
      a substantial mortality rate despite the use of PSA-based screening. Furthermore,
      therapy for prostate cancer by surgery, radiotherapy or hormonal manipulation
      carries a significant risk of treatment-related morbidity. Recent analysis of
      secondary endpoints of several large-scale randomized prospective clinical trials
      for other malignancies has suggested that selenium or vitamin E may result in a
      decreased incidence and mortality from prostate cancer. In vitro and preclinical
      studies of these antioxidants support this hypothesis. This review outlines the
      rationale and design of SELECT, the Selenium and Vitamin E Cancer Prevention
      Trial, designed to test the hypothesis that selenium or vitamin E alone or in
      combination can reduce the clinical incidence of prostate cancer in a population
      based cohort of men at risk. SELECT is a phase III, randomized, double-blinded,
      prospective, 2x2 factorial clinical trial which will randomize 32,400 healthy men
      with normal DRE and serum PSA to one of four study arms: selenium alone, vitamin
      E alone, selenium+vitamin E, or placebo. Study agents will be taken orally for a
      minimum of 7 and maximum of 12 y with assessments of general health, incident
      prostate cancer and toxicity performed at 12 month intervals. Under the
      assumptions described, the detectable risk reduction is 25% for an effective
      single agent relative to placebo, with an additional 25% reduction for the
      combination relative to an effective single agent. The estimated power for the
      comparison of a single agent vs placebo is 96% and the power for the comparison
      of an effective single agent vs combination is 89%. Secondary endpoints will
      include prostate cancer-free survival, all-cause mortality, and the incidence and
      mortality of other cancers and diseases potentially impacted by the chronic use
      of selenium and vitamin E. Other trial objectives will include periodic quality
      of life assessments, assessment of serum micronutrient levels and prostate cancer
      risk, and studies of the evaluation of biological and genetic markers with the
      risk of prostate cancer. Prostate Cancer and Prostatic Diseases (2000) 3, 145-151

PMID- 12497091
TI  - Interpretation of the ALLHAT interim analysis and implications for the treatment
      of patients with BPH.
AB  - The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) was designed to see if the effects of doxazosin, amlodipine and
      lisinopril were superior to those of chlorthalidone on the incidence of
      cardiovascular disease in high-risk patients with hypertension. Earlier this
      year, following an interim analysis of 24,335 patients, the doxazosin treatment
      arm was stopped amid reports of an increased incidence of secondary
      cardiovascular endpoints relative to chlorthalidone. This paper will offer some
      insight into the interpretation of the ALLHAT interim data, and clarify any
      issues around the use of alpha-1 adrenoceptor antagonists, such as doxazosin, in
      the management of patients with benign prostatic hyperplasia. Prostate Cancer and
      Prostatic Diseases (2000) 3, 152-156

PMID- 12497092
TI  - Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review.
AB  - We present a review of the epidemiological evidence for relations of prostate
      cancer risk to circulating total and bioavailable androgens, to alterations in
      the metabolism of insulin-like growth factor-1 (IGF-1), and to anthropometric
      indices of longitudinal growth (body stature) and overweight. In addition, we
      review the physiological inter-relationships between insulin, growth hormone/IGF
      1 axis, and sex steroid metabolism, as well as the associations of bioavailable
      sex steroid levels with overweight and obesity. A first conclusion of this review
      is that, taken together, epidemiological studies have provided little support for
      the hypothesis that prostate cancer risk is increased in men with elevated total
      or biovailable testosterone (T). Although one prospective study showed an
      increased risk in men with low plasma sex hormone-binding globulin (SHBG) and
      with elevated plasma T for given levels of SHBG, this was not confirmed by
      results from other cohort studies. A second conclusion is that overweight, which
      is generally associated with moderate reductions in both total and bioavailable
      plasma T, appears to be unrelated to any significant increase or decrease in
      prostate cancer risk. However, significant increases in risk have been observed
      for men with a taller body stature, or with elevated plasma IGF-1. IGF-1 may
      directly enhance prostate tumorigenesis by inhibiting apoptosis and by
      stimulating cell proliferation. In addition, IGF-1 downregulates the synthesis of
      SHBG, and enhances sex steroid synthesis. Therefore, we do not entirely rule out
      that due to an elevation of plasma IGF-1 levels, men at increased risk of
      prostate cancer also have mildly elevated plasma bioavailable T, which
      epidemiological studies may have failed to demonstrate because of methodological
      problems. Prostate Cancer and Prostatic Diseases (2000) 3, 157-172

PMID- 12497093
TI  - Serum IGF-1 determination in relation to prostate cancer screening: possible
      differential diagnosis in relation to PSA assays.
AB  - Prostate Cancer and Prostatic Diseases (2000) 3, 173-175

PMID- 12497094
TI  - Risk perceptions among patients and their relatives regarding prostate cancer and
      its heredity.
AB  - We performed a qualitative study to examine how prostate cancer (PC) patients and
      their spouses and relatives take into account family history when considering
      susceptibility to PC. Semi-structured interviews were conducted with 20
      participants. All interviews were tape-recorded, transcribed and content
      analyzed. Patients' and spouses' views concerning the seriousness of PC were
      different. Wives viewed PC as a serious disease because it has affected their
      marital relationships; patients found PC to be less serious because it can be
      treated. All participants viewed PC as a male disease that can be passed on from
      fathers to sons. Furthermore, participants were aware of PC clustering in their
      families. However, this awareness did not encourage (healthy) male relatives to
      seek early detection. Additionally, participants perceived age, high-fat diet,
      and less exercise as important risk factors, while socioeconomic status, ethnic
      origin and a family history of PC were viewed as less important. We recommend
      that health educators pay special attention to these findings when planning to
      teach patients, spouses and their relatives about PC, its heredity and risks.
      Prostate Cancer and Prostatic Diseases (2000) 3, 176-185

PMID- 12497095
TI  - The role of pretreatment serum albumin to predict pathological stage and
      recurrence among radical prostatectomy cases.
AB  - Serum albumin level has been implicated as a prognostic factor in various
      cancers, however it has not been studied in early stage prostate cancer. We
      examine the clinical prognostic value of the readily available pretreatment
      albumin level as a marker for determining staging and prognosis for men
      undergoing radical prostatectomy. A retrospective review was performed on 354
      patients who underwent a radical prostatectomy at a tertiary facility from 15
      April, 1990 until 3 December, 1996 who had a pretreatment serum albumin within 6
      months prior to surgery. Albumin levels were analyzed and compared to the values
      of standard prognostic factors to assess the ability of albumin to predict
      pathological stage and serological recurrence by PSA level after radical
      prostatectomy. Albumin level was not of value in predicting serological disease
      recurrence, but interestingly was an independent prognostic factor in predicting
      risk of nonorgan-confined disease (T3 or T4). Our data also showed that, as
      expected, grade and pretreatment PSA levels were independent predictors of
      pathological stage. Albumin appears to be of clinical utility to augment
      assessment of pretreatment pathological stage. However, it is not of value in
      predicting serological disease recurrence following radical prostatectomy.
      Further study in other cohorts and in using additional analysis such as neural
      networks is indicated. Prostate Cancer and Prostatic Diseases (2000) 3, 186-190

PMID- 12497096
TI  - Long-term stability of alpha-1-antichymotrypsin complexed form of prostate
      specific antigen.
AB  - PSA complexed with alpha-1-anti-chymotrypsin (cPSA trade mark ) is the moiety in
      greatest proportion in the serum of men with prostate cancer (CAP). The
      performance of this analyte has been established primarily in retrospective
      archival serum. Studies indicate cPSA trade mark provides the specificity
      enhancement of the free-to-total PSA ratio, yet obviates the need to measure two
      markers. In the present investigation we sought to establish the stability of
      cPSA trade mark with long-term storage. Serum from men undergoing ultrasound
      guided biopsy was utilized. Serum was assayed soon after collection and 18 months
      later. All serum was initially aliquotted and stored at -80 degrees C. There was
      no freeze-thaw. cPSA trade mark was measured utilizing the Bayer Immuno 1 method
      according to manufacturer's recommendations. The mean (s.d.) PSA was 5.5 (3.8)
      and 5.6 (3.9) ng/ml at the initial and subsequent testing, respectively. The
      medians were 4.3 and 4.4 ng/ml, respectively. No significant differences exist
      between the two determinants (r(2)=1.0, slope=1.01, t-test P=0.9194). These data
      establish for the first time the long-term stability of cPSA trade mark.
      Retrospective studies performed on archival material should give meaningful
      results. Prostate Cancer and Prostatic Diseases (2000) 3, 191-194

PMID- 12497097
TI  - Early urodynamic effects of the lipido-sterolic extract of Serenoa repens
      (Permixon(R)) in patients with lower urinary tract symptoms due to benign
      prostatic hyperplasia.
AB  - This prospective, controlled study was undertaken to evaluate the early
      urodynamic and symptomatic impact of the lipido-sterolic extract of Serenoa
      repens (Permixon(R) ) in the treatment of patients with benign prostatic
      hyperplasia (BPH). A total of 75 patients, aged 52-78 y with lower urinary tract
      symptoms due to mild/moderate BPH (mean International Prostate Symptom Score (I
      PSS) 8.2) were included in the study, of which 57 received Permixon(R) 160 mg
      twice daily for 9 weeks. Urodynamic evaluation, including maximum urinary flow
      rate (Q(max)) and detrusor pressure (DP), was performed at baseline and endpoint.
      Prostate volume and post-void residual urine volume were assessed by transrectal
      and transabdominal ultrasound respectively. In addition, the I-PSS and its
      associated quality of life (QoL) score were determined and adverse events were
      recorded. Baseline parameters were comparable between the active treatment and
      control groups. After 9 weeks of Permixon(R) treatment Q(max) increased (6.0%,
      P<0.001), and there were reductions in DP at maximum flow (12.8%, P<0.001),
      opening DP (12.6%, P<0.001), and residual urine volume (12.6%, P<0.05). In
      addition, the I-PSS and QoL score both decreased significantly from baseline in
      the active treatment group (26.8% and 18.2% respectively, P<0.001). None of these
      parameters improved significantly in control patients. There were also
      improvements in prostate volume (2.7%) and maximum DP (5.2%) in the Permixon(R)
      group which did not reach significance. Three patients receiving Permixon(R)
      experienced gastrointestinal disturbances but these did not lead to withdrawal or
      require additional therapy. In patients with mild/moderate BPH, Permixon(R)
      treatment reduced infravesical obstruction and produced a rapid improvement in
      urodynamic parameters and symptoms. The drug was well tolerated. These data
      support the use of Permixon(R) as first-line therapy in patients with
      uncomplicated symptomatic BPH. Prostate Cancer and Prostatic Diseases (2000) 3,
      195-199

PMID- 12497098
TI  - Prostate specific antigen measurements after minimally invasive surgery of the
      prostate in men with benign prostatic hypertrophy.
AB  - There is a trend of minimally invasive surgery in the treatment of benign
      prostatic hypertrophy (BPH). Studies have examined levels of prostate specific
      antigen (PSA) in patients after open prostatectomy or transurethral resection of
      prostate (TURP) and noted reset of PSA to lower values after surgery. We reviewed
      PSA levels in patients after minimally invasive procedures to determine if levels
      were reset. There were 120 patients (age 45-70) enrolled in the study. Fifty
      patients underwent laser ablation, 20 patients had electrovaporization (TVP) and
      50 patients underwent TURP. PSA measurements were obtained prior to and after
      surgical procedures in a three-year follow-up. Mean pre-operative PSA was 2.8 (+/
      0.34) ng/ml for laser cohort, 3.2 (+/-0.31) ng/ml for the TURP group and 2.3 (+/
      0.42) ng/ml for TVP patients (P=0.33). At 1 y follow-up, mean PSA decreased 32%
      for laser patients, 46% for the TURP cohort and 8% for TVP group. The largest
      mean decrease in PSA velocity was-1.5 (+/-0.31) ng/ml per y for TURP followed by
      0.9 (+/-0.29) ng/ml per y for laser patients and-0.1 (s.d.+/-1.2) ng/ml per y for
      TVP group in y 1. The TURP group maintained the largest decrease in PSA velocity
      in y 2,-0.6 (+/-0.26) ng/ml per y. Three patients (2-TURP, 1-TVP) were diagnosed
      with prostate cancer during follow-up. In conclusion, serum PSA levels were reset
      at lower levels following different surgical interventions. This lower level of
      PSA remained decreased for 2 y post-procedure. Urologists should be cognizant of
      this reset level and monitor PSA levels for possible increases to screen for
      prostate cancer in this patient population. Prostate Cancer and Prostatic
      Diseases (2000) 3, 200-202

PMID- 12497099
TI  - Maximum androgen blockade: a case study report.
AB  - The use of maximum androgen blockade (MAB) in advanced prostate cancer remains
      controversial due to conflicting data from clinical trials. Some of the trials
      that report no advantage of MAB over monotherapy have been criticized on a number
      of points, including a lack of statistical power and too short a follow-up
      period. Three randomized trials, SWOG-INT 0036, EORTC-30853 and the Anandron
      Study Group Trial, report a survival advantage and a longer time to disease
      progression with MAB, although only one reaches statistical significance. The
      widespread use of MAB is controversial on the basis of the available clinical
      data. It has been suggested that three clinical situations exist for its use in
      advanced cancer: in symptomatic disease; as neoadjuvant therapy prior to
      radiotherapy; and for the prevention of flare following the use of luteinizing
      hormone-releasing hormone analogues as monotherapy. Case studies are presented in
      this article involving the use of MAB in these circumstances, as well as its use
      under other conditions. MAB fits into an algorithm of progressive step-up therapy
      and by tailoring hormonal therapy to individual patients and their tumours we may
      improve survival and define further the future role of MAB. Prostate Cancer and
      Prostatic Diseases (2000) 3, 203-212

PMID- 12497100
TI  - What's hot in the prostate?

PMID- 12497101
TI  - Prostate cancer: are new prognostic markers on the horizon?
AB  - Current diagnostic methods in prostate cancer are lacking in their ability to
      predict individual patient outcome which highlights the need for more sensitive
      prognostic markers. Biological markers are seen as attractive and relevant
      candidates in current efforts to improve prognostic methods. Since metastasis is
      the most important component of cancer progression and mortality, markers which
      are able to predict the likely acquisition of the metastatic phenotype, before
      the onset of metastases, would be extremely useful clinically. This review
      outlines various metastasis suppressor genes and metastasis promoters which might
      have potential prognostic use in prostate cancer. Prostate Cancer and Prostatic
      Diseases (2000) 3, 62-65

PMID- 12497102
TI  - MRP1 not MDR1 gene expression is the predominant mechanism of acquired multidrug
      resistance in two prostate carcinoma cell lines.
AB  - Multidrug resistant prostate cancer cell lines DU 0.03 and PC 0.03 were
      established from the parental prostate cancer cell lines DU145 and PC-3
      respectively by stepwise selection in doxorubicin (DOX) from 0.001 to 0.03
      &mgr;g/ml. As cells adapted to each concentration of DOX. the drug concentration
      was increased by 0.001 &mgr;g/ml. The chemosensitivity of each line was
      determined by growth inhibition assay. The DU 0.03 and PC 0.03 lines exhibit a 5
      10-fold and 1.3-2.8-fold increase in resistance to anthracyclines, vinblastine
      (VLB) and mitozantrone (Mito), respectively. Verapamil (5 &mgr;M) partially
      reversed the resistance to the anthracycline and completely reversed the
      resistance to VLB and Mito. Drug kinetic studies measured by intracellular
      accumulation of (3)H-daunorubicin demonstrated a 3 fold decrease in the level of
      intracellular (3)H-daunorubicin in the PC 0.03 and DU 0.03 resistant lines
      compared with their respective parental line. This effect was partially reversed
      by 5 &mgr;M verapamil. The expression of MDR1 and MRP genes was analysed by
      Northern blotting and RT-PCR. P-glycoprotein (Pgp) and MRP protein were tested by
      immunocytochemistry staining using the monoclonal antibodies J-SB1. C219 and
      MRK16 (Pgp) and MRPm6 and MRPr1 (MRP). Neither Northern blot analysis nor the
      more sensitive RT-PCR demonstrated detectable MDR1 transcripts in any of the
      prostate cancer cell lines and the three Pgp monoclonal antibodies failed to
      reveal expression of Pgp. A 2-4-fold increase in MRP1 mRNA levels in the drug
      resistant DU 0.03 and PC 0.03 lines were demonstrated by both Northern blotting
      and RT-PCR consistent with the findings observed after staining by the two
      specific monoclonal antibodies, MRPm6 and MRPr1. Southern blot analysis
      demonstrated a 2-fold increase in the MRP1 gene copy number in the PC 0.03 line
      but not in the DU 0.03 line, suggesting that the overexpression of the MRP gene
      was regulated at the level of transcription in the latter line. We conclude that
      MRP1 not MDR1 overexpression. contributes to acquired drug resistance in these
      two prostate cancer cell lines. Prostate Cancer and Prostatic Diseases (2000) 3,
      66-75

PMID- 12497103
TI  - alpha(1)-Adrenoceptor selectivity and the treatment of benign prostatic
      hyperplasia and lower urinary tract symptoms.
AB  - The storage (irritative) and voiding (obstructive) symptoms associated with
      benign prostatic hyperplasia are generally attributed to prostate enlargement and
      increased prostatic smooth muscle tone mediated by the prevailing alpha(1)
      adrenoceptors in the bladder neck and prostate. This results in obstruction and
      subsequent secondary changes to the bladder. However, there is growing evidence
      that many of these symptoms may be due to changes in extraprostatic alpha(1)
      adrenoceptors, possibly alpha(1D)-adrenoceptors. Findings from the VA cooperative
      trial challenge the current theory that the common side effects associated with
      these agents are due to vascular action of alpha(1)-adrenoceptor blockers.
      Prostate Cancer and Prostatic Diseases (2000) 3, 76-83

PMID- 12497104
TI  - Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces
      apoptosis in both androgen-dependent and androgen-independent prostate cancer
      cells.
AB  - In an effort to find an alternative nontoxic means of inducing the apoptosis
      potential in both androgen-dependent and hormone refractory prostate cancer
      cells, attention was focused on curcumin (turmeric), traditionally used in
      medicine and cuisine in India and other south-east Asian countries. The results
      indicate that curcumin is a novel and potent inducer of apoptosis in both
      androgen-dependent and androgen-independent prostate cancer cells. This was
      accomplished by down-regulating apoptosis suppressor proteins and other crucial
      proteins such as the androgen receptor. It is concluded that curcumin may provide
      an alternative, nontoxic modality by which the clinician may prevent the
      progression of prostate cancer to its hormone refractory state or to treat
      advanced prostate cancer by forcing them to undergo apoptosis. Prostate Cancer
      and Prostatic Diseases (2000) 3, 84-93

PMID- 12497105
TI  - Nonaggressive management of White and Black prostate cancer patients in the
      United States.
AB  - Appropriate treatment for prostate cancer is controversial because of the lack of
      information from randomized clinical trials indicating the benefits of one
      treatment over another. Watchful waiting or conservative management remains an
      alternative for this disease. This paper assesses the extent to which White and
      Black prostate cancer patients in the USA choose nonaggressive therapy.
      Nonaggressive therapy is defined as patients not receiving cancer-directed
      surgery or radiation, or that undergo a transurethral resection of the prostate
      (TURP)/simple prostatectomy but no radiation. Of 112,445 prostate cancer patients
      diagnosed in 1992-1996, 40% Whites and 46% Blacks were not aggressively treated.
      Approximately 28% Whites and 33% Blacks did not receive cancer-directed surgery
      or radiation, and 12% Whites and 13% Blacks underwent a TURP/simple prostatectomy
      but no radiation. Stage, histologic grade and age at diagnosis, race (White and
      Black), and number of cancer primaries each significantly influence how patients
      are managed. Black patients are more likely than White patients to forego
      aggressive therapy, even after adjusting for less preferential stage and
      histologic grade at diagnosis, as well as differences in age and number of cancer
      primaries. Explanations for this result deserve further consideration. Prostate
      Cancer and Prostatic Diseases (2000) 3, 94-99

PMID- 12497106
TI  - Ultrasound-guided seminal vesicle biopsies in prostate cancer.
AB  - Invasion of prostatic adenocarcinoma into the seminal vesicles (SV) is generally
      accepted as an index of poor prognosis. The pre-operative identification of SV
      invasion is an important element in staging since it may alter subsequent
      treatment decisions. We studied the possibility of diagnosing SV invasion with
      two biopsies from the junction between the prostate and seminal vesicles. Also we
      studied the correlation of several prognostic factors with the risk of clinical
      stage T(1,2,3) prostate cancer patients of having cancer growth into the seminal
      vesicles. Consecutive patients referred for transrectal ultrasound (TRUS) and
      biopsy because of clinical suspicion of prostate cancer were examined. This
      staging procedure was evaluated in patients who underwent a pelvic
      lymphadenectomy and radical retropubic prostatectomy (RRP). In 83 out of 138
      patients prostate cancer was detected whereas 55 patients had benign disease. In
      44% of prostate cancer patients a positive SV biopsy was found. The accuracy of
      the biopsies adjacent to the junction of the SV and the prostate was 91%. The
      best predictors for SV invasion were tumor grade of the biopsy sample (P<0.001),
      serum prostate-specific antigen (PSA) (P<0.0005), PSA density (P<0.0005) and
      clinical stage (P<0.0005). No significance was found in the relation to seminal
      vesicle involvement with free/total (f/t) PSA ratio (P=0.588) for the prostate
      cancer group (SV+ and SV-). In a receiver operating characteristic curves
      analysis, PSA density was significantly more accurate for prediction of SV
      invasion than PSA or f/t PSA ratio. In five prostatectomized patients (and
      negative SV biopsy) no SV invasion was found in the final pathologic examination
      either. SV biopsy at the junction of the SV and prostate is accurate for staging
      with high efficacy and low morbidity. To predict SV invasion in prostate cancer
      patients, PSA density was more accurate than PSA or f/t PSA ratio. The
      determination of the f/t PSA ratio in patients with low and intermediate PSA
      levels (eg <15 &mgr;g/L) is not useful to estimation of the risk of seminal
      vesicle involvement. The combination of serum PSA concentration, PSA density,
      tumor grade from the biopsy specimens ad clinical stage provides the best
      prediction of SV invasion. These parameters are identical to the conventional
      predictors of pathology after RRP. SV biopsies may provide additional
      information; if one or both basal biopsies are positive, a clinical T(1,2)
      disease is altered to T(3). Hence SV biopsy is useful for selection of patients
      who might obtain good results from RRP for prostate cancer. Prostate Cancer and
      Prostatic Diseases (2000) 3, 100-106

PMID- 12497107
TI  - Apolipoprotein E genotype is not linked to locally recurrent hormone-refractory
      prostate cancer.
AB  - Mechanisms of prostate cancer recurrence during androgen deprivation are poorly
      understood. Recently, the putative role of apolipoprotein E varepsilon 4 allele
      in the aetiology of prostate cancer was raised. To investigate the hypothesis
      that varepsilon 4 allele of apolipoprotein E gene predisposes to prostate cancer
      and is involved in the relapse of hormonal therapy response, 38 hormone
      refractory locally recurrent carcinoma samples from 38 prostate cancer patients
      were screened for apolipoprotein E genotype. The frequency distribution of
      apolipoprotein E genotypes among tumours did not differ significantly from that
      among controls. The allele frequency of varepsilon 4 was 19.7% and 19.3% in
      tumours and controls, respectively. The results suggest that clinical progression
      of prostate cancer during androgen withdrawal therapy is not associated with
      apolipoprotein E genotype. Prostate Cancer and Prostatic Diseases (2000) 3, 107
      109

PMID- 12497108
TI  - Genetic alterations in microdissected prostate cancer cells by comparative
      genomic hybridization.
AB  - Molecular genetic abnormalities were assessed on 23 cases of prostate
      adenocarcinoma by performing microdissection on archived tumor tissue sections
      followed by degenerate oligonucleotide primed PCR (DOP-PCR) on extracted DNA,
      providing sufficient product to carry out comparative genomic hybridization
      (CGH). The results of CGH show a significant regional DNA copy number alteration
      in 100% of the cases. Copy number gains were detected most frequently in
      chromosome 8q (91.3%), followed by chromosome X (43.5%), and chromosomes 20, 7,
      4, and 3 (8.7%). DNA copy number losses occurred most frequently in chromosome 18
      (34.8%), followed by chromosome 20 (21.7%), chromosomes 16 and 22 (17.4%) and
      chromosomes 12, 17, and 19 (8.7%). Since tissue microdissection and DOP-PCR
      yields product for analysis that represents DNA from pure tumor cells. CGH shows
      high sensitivity in detecting copy number alterations. This method indicates
      regions of the genome that are likely to be driven to amplification or deletion
      by the presence of oncogenes or tumor suppressor genes, respectively. The most
      common alteration detected was a regional gain in copy number in chromosome 8
      near 8q21, indicating an oncogene in this region may be key to development of
      prostate adenocarcinoma. Prostate Cancer and Prostatic Diseases (2000) 3, 110-114

PMID- 12497109
TI  - Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis
      induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB).
AB  - The objective of this study was to determine the effects of androgen depletion by
      5alpha-reductase inhibitor (eg epristeride), pure antiandrogen (eg casodex) or
      C17-20 lyase inhibitor (eg YM116) on rat prostate carcinogenesis induced by
      administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB). DMAB was subcutaneously
      administered on male F344 rats for the first 20 weeks. Epristeride (10 and 50
      mg/kg, three times per week), casodex (15 and 30 mg/kg, three times per week) or
      YM116 (15 and 30 mg/kg, three times per week) were administered orally for 40
      consecutive. Then, all accessory sex organs were studied for the formation of
      neoplastic lesions by histological examination. All carcinoma lesions were
      produced only in the ventral lobe of the prostate. The incidence of carcinoma
      developing in the ventral lobe of the prostate was 9.5% in the control group on
      which DMAB alone was administered, whereas it was 31.6% in the epristeride 10
      mg/kg group. 45.0% in the epristeride 50 mg/kg group, 47.8% in the casodex 15
      mg/kg group, 63.2% in the casodex 30 mg/kg group, 10.5% in the YM116 15 mg/kg
      group and 5.0% in the YM116 30 mg/kg group. The incidences of carcinoma in the
      epristeride 10 mg/kg group, casodex 15 mg/kg group and casodex 30 mg/kg group
      were significantly higher than that of the control group. In this experimental
      model, all ventral prostate carcinomas were in situ adenocarcinomas that did not
      form palpable nodules or distant metastasis. Epristeride and casodex showed a
      dose-dependent promoting effect on rat ventral prostate carcinogenesis. These
      results were contradictory to the results of our previous studies; exogenous
      testosterone in combination with DMAB produced palpable, and metastatic tumors in
      other portions of accessory sex organs of F344 rats but no carcinoma in ventral
      prostate, and those invasive carcinomas were significantly inhibited by 5alpha
      reductase inhibitor and nonsteroidal anti-androgen. The action mechanisms of
      androgen and the effects of androgen-regulatory drugs on prostate carcinogenesis
      should be further studied. Prostate Cancer and Prostatic Diseases (2000) 3, 115
      119

PMID- 12497111
TI  - Innovators in Urology 2000.

PMID- 12497110
TI  - (The British Prostate Group Spring Meeting, 16-17 March 2000, The Swallow Royal
      Hotel, Bristol).

PMID- 12497112
TI  - Novel biochemical markers for the endocrine management of prostate cancer: serum
      chromogranin A and interleukin-6.

PMID- 12497113
TI  - Prostate biopsy strategies in the United Kingdom.

PMID- 12497114
TI  - Volume-weighted mean nuclear volume predicts tumour biology after radical
      prostatectomy.

PMID- 12497116
TI  - The role of radical prostatectomy in patients with PSA of 20 or greater and/or a
      prostate biopsy with a total Gleason sum of 8 or greater.

PMID- 12497115
TI  - Adenoviral mediated gene therapy for prostate cancer: studies on vector tropism
      and payload.

PMID- 12497117
TI  - Studies on phenotypic expression patterns of proteases and protease inhibitors in
      benign compared to malignant prostate tissues.

PMID- 12497118
TI  - Invasive phenotype of primary human prostatic epithelial cells.

PMID- 12497119
TI  - Correlation of serum prostate specific antigen and semi quantitative tissue RT
      PCR from prostate cancer samples.

PMID- 12497120
TI  - The role of adenoviral vectors in genetic prodrug activation therapy in prostate
      cancer.

PMID- 12497121
TI  - Use of pretreatment prostate specific antigen doubling time to predict outcome
      after radical prostatectomy.

PMID- 12497123
TI  - Serum and tissue lycopene and biomarkers of oxidation in prostate cancer
      patients: a case control study.

PMID- 12497122
TI  - Regulation of angiogenesis in human prostate cancer.

PMID- 12497124
TI  - Does adjuvant hormonal treatment with goserelin acetate depot 3.6 mg modify 5
      years disease free survival in patients with pathological 'C stage' prostate
      cancer at radical retropubic prostatectomy?

PMID- 12497125
TI  - New treatments based on gene therapy approaches to increase radiosensitisation in
      prostate cancer.

PMID- 12497126
TI  - Castration-induced upregulation of insulin-like growth factor binding protein-5
      potentiates IGF-1 and accelerates androgen-independent progression in prostate
      cancer.

PMID- 12497127
TI  - Methylation-specific PCR (MSP) for detection of tumour DNA in the blood plasma
      and serum of patients with prostate cancer.

PMID- 12497128
TI  - A validated strategy to select patients for a nerve-sparing radical
      prostatectomy.

PMID- 12497130
TI  - Intermittent androgen suppression in the management of prostate cancer: a phase
      II comparative study.

PMID- 12497129
TI  - Ratio free/total PSA (%f-PSA) in men with total PSA 0.5-3 ng/ml: improvement for
      prostate cancer detection?

PMID- 12497131
TI  - The impact of sexual and urinary dysfunction on health-related quality-of-life
      (HRQOL) following radical prostatectomy (RP).

PMID- 12497132
TI  - A prospective comparison of anatomic radical perineal and retropubic
      prostatectomy specimens: are surgical margins equivalent?

PMID- 12497133
TI  - Detection of viral HPV 16 DNA in prostate cancer and benign prostatic hyperplasia
      by quantitative PCR-directed analysis.

PMID- 12497134
TI  - Induction of apoptosis by alpha1-adrenoceptor antagonists in benign prostatic
      hyperplasia and prostate cancer.

PMID- 12497135
TI  - A prospective, longitudinal study of the short-term effects of brachytherapy vs
      radical prostatectomy on health-related quality of life.

PMID- 12497136
TI  - P53 regulated maspin protein expression determines recurrence-free survival of
      patients with localised prostate cancer.

PMID- 12497137
TI  - Molecular staging of prostatic cancer with RT-PCR assay for PSA in peripheral
      blood and lymph nodes. Comparison with standard histological staging and
      immunohistochemical assessment of occult regional lymph node metastases.

PMID- 12497138
TI  - cDNA microarray gene chip for prostate cancer and translational study in a
      prospective tissue bank and clinical longitudinal database.

PMID- 12497139
TI  - Treatment of prostate cancer-use of specific monoclonal antibodies.

PMID- 12497140
TI  - PTEN/MMAC1 mutations in prostate cancer.

PMID- 12497141
TI  - Sural nerve graft during non-nerve-sparing radical retropubic prostatectomy
      restores erectile function in patients with locally advanced prostate cancer.

PMID- 12497142
TI  - Pubourethral sling simultaneous with radical retropubic prostatectomy for
      patients at high risk for postprostatectomy incontinence.

PMID- 12497143
TI  - Ten systematic transrectal-guided prostate re-biopsies in patients with a
      negative prostatic biopsy.

PMID- 12497144
TI  - Global analysis of differential gene expression between prostate cancer and
      normal prostate tissues using cDNA microarray of open-reading frame expressed
      sequence tags (ORESTES).

PMID- 12497145
TI  - Oedematous swelling of the prostate as a result of seed implantation: impact on
      dosimetry in T1/T2 tumours.

PMID- 12497146
TI  - The role of androgen receptor coactivators in prostate cancer growth.

PMID- 12497147
TI  - Transformation dependent signalling pathways leading to transcriptional induction
      of vascular endothelial growth factor in prostate cancer.

PMID- 12497148
TI  - Augmented cytotoxicity of estramustine in prostate cancer cell lines by N-acetyl
      L-cysteine.

PMID- 12497149
TI  - The influence of psychosocial factors on the measured quality of life (QoL) in
      patients suffering from benign prostate hyperplasia (BPH) and patients with
      prostate cancer (PC).

PMID- 12497150
TI  - Insulin-like growth factor-1 alters apoptotic signalling in prostate cancer.

PMID- 12497151
TI  - Tumour angiogenesis as a target for adenoviral mediated antisense gene therapy in
      human prostate cancer.

PMID- 12497152
TI  - Delegate list.

PMID- 12497154
TI  - What's hot in the prostate?

PMID- 12497155
TI  - Cell adhesion and chemotaxis in prostate cancer metastasis to bone: a minireview.
AB  - Bone metastasis is a common phenomenon in patients with advanced prostate cancer.
      The molecular and cellular mechanisms involved in this process are not well
      understood. Past reviews on this subject primarily focused on prostate tumor
      growth in the bone marrow and the effects this growth has on bone homeostasis (ie
      osteoblastic and osteolytic). Cell chemotaxis and adhesion are also important for
      site-specific metastasis. In this review we have focused on chemotactic and cell
      adhesion molecules potentially involved in prostate cancer metastasis to bone. In
      addition, recently developed animal models for prostate cancer metastasis to bone
      are discussed. Prostate Cancer and Prostatic Diseases (2000) 3, 6-12

PMID- 12497156
TI  - Diagnostic dilemmas in detection of prostate cancer in patients undergoing
      transrectal ultrasound-guided needle biopsy of the prostate.
AB  - Transrectal ultrasound (TRUS)-guided needle biopsy of the prostate is a widely
      practised method for obtaining high quality tissue cores for histological
      diagnosis in men with suspected prostate cancer. Technological advances such as
      high-resolution hand held probes with biplanar imaging capabilities and spring
      loaded needles that easily permit multiple biopsies to be obtained have ensured
      that this technique has rightly taken its place at the forefront of prostate
      cancer diagnosis. However, the capacity for TRUS to identify prostate cancer
      remains limited because of poor specificity and variability in the ultrasonic
      appearance of tumours. Widespread prostate-specific antigen (PSA) testing has
      increasingly resulted in greater numbers of tumours being diagnosed at an early
      stage, when they are clinically impalpable and ultrasonically indistinguishable
      from surrounding normal prostate tissue. In this setting, the principal role for
      TRUS is to facilitate systematic sampling of all relevant zones of the prostate.
      Despite advances in technology and in our understanding of this disease, a number
      of diagnostic dilemmas arise. Should we perform lesion-directed or random
      biopsies? How many tissue cores should be obtained for optimal diagnostic yield,
      to reduce the incidence of false-negative biopsies? What areas of the prostate
      should be biopsied to give the best diagnostic results? If the initial biopsies
      fail to detect cancer, who should undergo repeat biopsy? Some have also voiced
      concern that TRUS risks identifying clinically insignificant disease. Here, we
      review the studies that have addressed these issues and have lead to the
      evolution of TRUS-guided prostate biopsy into an essential tool in the detection
      of carcinoma of the prostate. Prostate Cancer and Prostatic Diseases (2000) 3, 13
      20

PMID- 12497157
TI  - Tailoring of hormonal therapy in prostate cancer.
AB  - With an increasing interest in the early introduction of hormonal therapy in
      patients who cannot be cured of their prostate cancer by radical surgery or
      radiotherapy, there is a need to consider the most patient-friendly, effective
      hormonal therapy at each stage of the disease, thereby hoping not only to improve
      the quantity of the patient's life but also to maintain a reasonable quality of
      life. With the development of new hormonal therapies such as non-steroidal
      androgens, LHRH-antagonists and differentiation agents, urologists need to look
      again at the hormonal status of their patients before prescribing an appropriate
      therapy. There is increasing evidence that at certain stages of the disease
      patients are prepared to trade off the length of life for improved quality and
      bearing this in mind there needs to be some substantial re-thinking over the most
      appropriate therapy, particularly at early stages of the patient's disease and
      following progression to the later stages. Prostate Cancer and Prostatic Diseases
      (2000) 3, 21-27

PMID- 12497158
TI  - Models for studying benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting
      aging man. Attempts have been made to clarify the etiology and pathogenesis and,
      to that end, experimental models have been developed. To date, in vitro and in
      vivo models have been used, depending on the concept of the study. Spontaneous
      animal models are limited to the chimpanzee and the dog. Ethical and financial
      factors restrict the applicability of these models. The hormonal-induced canine
      BPH model is a good alternative that closely resembles human BPH in many aspects.
      The experimental models currently used for studying BPH are reviewed. Prostate
      Cancer and Prostatic Diseases (2000) 3, 28-33

PMID- 12497159
TI  - Ganglion cells in the human prostate.
AB  - Prostate carcinoma infiltrating around ganglion cells is claimed to be diagnostic
      of extracapsular extension because ganglion cells are only found in periprostatic
      soft tissue. However, the presence of autonomic ganglion cells in the fibrous
      capsule of the prostate has been reported. In this study, we aimed to define the
      exact localization of the ganglion cells in radical prostatectomy specimens.
      Slides of 64 totally embedded radical prostatectomies were reviewed. The ganglion
      cells were noted as outside the gland if no relation could be defined with
      prostate capsule or prostatic glands. They were noted as in the capsule when
      ganglion cells were observed inside the capsule, which was easily and definitely
      discerned. Ganglion cells were noted as in the prostate when ganglion cells were
      observed beneath the capsule and in close proximity to the prostatic glands.
      Also, the ganglion cells were noted as in the capsule if they were observed
      inside the capsule but not adjacent to the prostatic glands, and as outside the
      prostate when the capsule could not be easily defined and distant from the
      prostatic glands. Ganglion cells were observed in the prostate in 12 cases
      (18.75%). There was no relationship of these ganglion cells with the tumor in the
      prostatectomy specimens. Ganglion cells were located in the capsule in 14 cases
      (21.9%). The ganglion cells were observed outside the prostate in the other 38
      cases (59.4%). These results show that there may be ganglion cells in the
      prostate. Therefore, defining ganglion cell invasion by the tumor as
      extracapsular invasion may lead to staging error and cause erroneous management
      of the disease. Presence of carcinoma in ganglion cells should be recorded by
      defining whether these structures are within or outside the prostate gland.
      Prostate Cancer and Prostatic diseases (2000) 3, 34-36

PMID- 12497160
TI  - Localized prostate cancer and 30 years of follow-up in a population-based
      setting.
AB  - Some patients with a histopathological diagnosis of prostate cancer have a tumour
      that behaves benignly during long-term follow-up. The proportion of patients with
      such a tumour is unknown, as is the fraction who die of prostate cancer between
      10 and 20 y of follow-up. All men aged 45-84 y obtaining a diagnosis of prostate
      cancer between 1965 and 1993 and being reported to the Finnish Cancer Registry
      were observed. Death was recorded as caused by prostate cancer or not. We
      identified 11,500 men with localized prostate cancer and in this group the
      disease-specific survival rate reached a plateau at approximately 30% after 23 y
      of follow-up. In the same cohort, 5% of the patients died of prostate cancer
      during years 11-20 of follow-up. During the observation period, somewhat less
      than half of the patients with localized prostate cancer who died, died of the
      disease. This proportion decreased with duration of follow-up. In conclusion,
      early aggressive therapy for localized prostate cancer is unnecessary, in terms
      of survival, for those with a benignly behaving tumour (about 30% in this series)
      or who die of intercurrent disease (about 50% in this series). Such therapy may,
      however, prolong life for the patients and may cure the patients that die of
      prostate cancer after more than 10 y follow-up. Prostate Cancer and Prostatic
      Diseases (2000) 3, 37-42

PMID- 12497161
TI  - Lateral biopsies added to the traditional sextant prostate biopsy pattern
      increases the detection rate of prostate cancer.
AB  - Urologists routinely use the systematic sextant needle biopsy technique to detect
      prostate cancer. However, recent evidence suggests that this technique has a
      significant sampling error and data based upon whole-mounted step-sectioned
      radical prostatectomy specimens using a three-dimensional computer-assisted
      prostate biopsy simulator suggests that an increased detection rate is possible
      using laterally placed biopsies. The simulated 10-core biopsy pattern
      (traditional sextant biopsy cores and four laterally placed biopsies in the right
      and left apex and mid portion of the prostate gland) was shown to be superior to
      the traditional sextant biopsy. The objective of this pilot study was to confirm
      the higher prostate cancer detection rate obtained using the 10-core biopsy
      pattern in patients. We reviewed data on 35 consecutive patients with a
      pathologic diagnosis of prostate cancer biopsied by a single urologist using the
      10-core biopsy pattern. The frequency of positive biopsy was determined for each
      core. Additionally, the sextant and 10-core prostate biopsy patterns were
      compared with respect to prostate cancer detection rate. Of the 35 patients
      diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy
      only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients
      being diagnosed solely with the laterally placed biopsies. The laterally placed
      biopsies had the highest frequency of positive biopsies when compared to the
      sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies
      based upon a five region anatomical model are superior to the routinely used
      sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3,
      43-46

PMID- 12497162
TI  - Imaging with prostate-specific membrane antigen (PSMA) in prostate cancer.
AB  - Radioimmunoscintigraphy using a radio-labelled antibody to prostate-specific
      membrane antigen (PSMA) has growing applications as a means of tissue-specific
      imaging based on functional characteristics and complements traditional staging
      investigations. Clinical applications in men with carcinoma of the prostate are
      being refined, and this study reports outcomes with this technique in our
      practice. Prostatic immunoscintigraphy scans were performed with In-111 CYT 356
      in 49 men with carcinoma of the prostate, obtaining sequential images in two and
      three dimensions at 10 min, 24 and 48 h. Of the 49 men, 36 had clinically
      localized cancer, 10 had recurrent disease after radical radiotherapy or radical
      prostatectomy and three had rising PSA after primary endocrine treatment. Scan
      findings are discussed in the context of clinical management. Of the 36 men with
      clinically localized cancer, seven had increased uptake in regional and distant
      lymph nodes. Of these seven, three were treated with hormone manipulation, two by
      radical prostatectomy and two by radical radiotherapy. Among 10 patients who had
      recurrence after radical treatment of the primary tumour, scans showed local
      recurrence alone in four, and six had regional or distant metastases. Three
      patients treated with primary hormone manipulation had scans for rising PSA, and
      of these one had a positive regional node and two had distant soft tissue and
      bone metastases. In conclusion, prostatic radio-immunoscintigraphy scans
      highlight tissues involved by prostate cancer, including the prostate, lymph
      nodes, soft tissues and bone metastases as well as pelvic recurrence. Results may
      contribute to the clinical management of individual patients, although
      histological confirmation may be appropriate when considering alternative
      treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 47-52

PMID- 12497163
TI  - Postradiation therapy adenosquamous cell carcinoma of the prostate.
AB  - The objective of this study was to present two cases of adenosquamous cell
      carcinoma of the prostate following radiation therapy. Two patients with history
      of prostate cancer treated with radiation therapy presented with rectal bleeding
      and a large ulcerated rectal mass. The rectal biopsy revealed on both cases
      squamous cell carcinoma. The initial diagnosis was invasive squamous cell
      carcinoma from anal origin. Both patients underwent pelvic exenteration with
      continent urinary diversion. After extensive histological sampling and immuno
      histochemisty, they were correctly diagnosed of adenosquamous cell carcinoma of
      the prostate with invasion of the rectum. The patients died 6 and 16 months after
      surgery with widespread metastases. A review of the literature is presented.
      Adenosquamous cell carcinoma of the prostate is an unusual histological variant
      of prostate cancer. To our knowledge, only three cases of adenosquamous cell
      carcinoma of the prostate following radiation therapy have been reported. The
      unusual clinical and histopathological features of the two cases reported here
      led to an initial mistaken diagnosis. Adenosquamous cell carcinoma of the
      prostate should be considered in the differential diagnosis when a patient with
      prostate cancer develops a rectal mass or rectal bleeding following radiation
      therapy and the rectal biopsy reveals squamous cell carcinoma. Prostate Cancer
      and Prostatic Diseases (2000) 3, 53-56

PMID- 12497165
TI  - Editorial.

PMID- 12497164
TI  - What's hot in the prostate? Prostate Cancer screening approved in the USA and
      Highlights from the Annual Meeting of The Western Section American Urological
      Association.

PMID- 12497166
TI  - Update in Prostatic Diseases First congress of CEAU, 5-6 November, Vienna,
      Austria.

PMID- 12497167
TI  - Artificial neural networks in urology: Update 2000.
AB  - Artificial neural networks (ANNs) are widely available and have been demonstrated
      to be superior to standard empirical methods of detecting, staging and monitoring
      prostate cancer. These algorithms have been statistically validated in diverse,
      well-characterized patient groups and are now being evaluated for clinical use
      worldwide. New variables based on demographic data, tissue and serum markers show
      promise for improving our ability to predict disease extent and outcome and may
      be integrated in future ANN models. This review focuses on recently developed
      neural networks for detecting, staging and monitoring prostate cancer.

PMID- 12497168
TI  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for treatment of
      prostate cancer: first results and review of the literature.
AB  - We present the involvement and association of TNF-related apoptosis-inducing
      ligand (TRAIL) with apoptosis. Its potential application as a therapeutic agent
      in urologic oncology is discussed. We have examined the sensitivity of prostate
      carcinoma cell lines DU145, PC3 and LNCaP to TRAIL-induced apoptosis and the
      expression of TRAIL receptors. Furthermore we looked into the sensitization of
      those prostate carcinoma cell lines to TRAIL-mediated apoptosis by low toxic
      levels of actinomycin-D. Furthermore, we review and discuss the pertinent
      literature on the molecular biology of TRAIL, its receptors and future potential
      for therapy in urologic oncology. Recent discovery and characterization of TRAIL
      has led to further broadening and insights into the apoptotic process. Based on
      preceding in-vitro studies, the first in-vivo study using TRAIL has been
      conducted and published in 1999. Systemic application of TRAIL in severe combined
      immune deficient (SCID) mice resulted in tumor regression of subcutaneous
      implanted mammary and colon cancer and several groups are looking into TRAIL
      sensitivity of prostate cancer and renal cancer cellines. Our in-vitro data
      revealed a significant increase of apoptotic cell death rate following the
      combined application of TRAIL with actinomycin-D. Our results suggest that the
      combination of TRAIL and ActD may be a therapeutic option in the treatment of
      drug/hormone refractory prostate carcinoma. In the future TRAIL may be used in
      combination therapy with other immunotherapies or gene therapies providing a
      synergistic effect or enhancing the efficacy of chemotherapeutic or
      radiotherapeutic regimens.

PMID- 12497169
TI  - Prostatitis.
AB  - The objective of this article is to present a detailed review of the
      international literature concerning both the already established and the most
      recent information about clinical picture, aetiology, classification, diagnosis
      and treatment of prostatitis. The symptomatology of the condition is non-specific
      and requires a wide spectrum of diagnostic tools in order the clinician be able
      to reach a firm conclusion. A novel classification system is outlined, with
      already established international reputation. The treatment of the various
      chronic types is often empirical and the available therapies need controlled
      studies in order to achieve an established status in Urologist's armamentarium.
      Finally it is emphasized that continuous research addressing to aetiology,
      pathogenesis, diagnosis and treatment is of paramount importance in answering
      questions and shedding light on this obscure syndrome.

PMID- 12497170
TI  - Transrectal ultrasound imaging of the prostate: review and perspectives of recent
      developments.
AB  - We present a critical review of the recent literature and discuss the development
      and prospective view of the evaluations of transrectal ultrasound with regard to
      prostate malignancy. We illustrate this with personal experiences. Material and
      Methods: Based on a critical evaluation of clinical data we address the apparent
      shortcoming of greyscale transrectal ultrasonography in the assessment of
      prostate cancer. New developments and future possibilities are also discussed.
      Evaluation of the value of greyscale transrectal ultrasonography in the diagnosis
      of prostate cancer indicates a limited role, because of the non-uniform
      appearance of prostate cancer on the ultrasound images. Ameliorating of
      transrectal ultrasound, like the use of contrast ultrasonography, could improve
      the detection of prostate cancer. Although the use of greyscale transrectal
      ultrasonography lacks sensitivity and specificity for the diagnosis of prostate
      cancer, its use in volume measurement of the prostate and biopsy guidance is
      unquestionable. The first results of the application of contrast ultrasonography
      are promising, both in detection of prostate cancer as in treatment follow up.
      Other developments like improvement of transducer and computer technology could
      make the use of ultrasound more versatile. However, future research will indicate
      whether all these improvements will lead to clinical applications.

PMID- 12497171
TI  - Morbidity in patients with clinically localized prostate cancer managed with non
      curative intent. A population-based case-control study.
AB  - To compare the morbidity in patients with newly diagnosed clinically localized
      prostate cancer managed conservatively with the morbidity in a randomly selected
      age-matched background population with no history of prostate cancer. Patients
      younger than 75 y at diagnosis with newly diagnosed clinically localized prostate
      cancer reported to the Danish Cancer Registry in the period 1977-1992. Morbidity
      in patients and age-matched controls was extracted from The Danish Hospital
      Discharge Registry. Admissions were stratified by discharge diagnosis. Overall
      4744 patients were hospitalized for 251,695 days within the first 10 y following
      diagnosis compared with 74,563 days in 4774 age-matched controls. The patients
      were admitted 6.7 (6.4-7.1) times more often than controls in the year following
      diagnosis, and 2.7 (2.6-2.8) times more often in the following 9 y. Excess
      morbidity declined over time. When prostate cancer-related admissions were
      excluded, the relative risk of admission was reduced to 1.35 (1.3-1.4) and 0.86
      (0.83-0.89), respectively. The estimated costs associated with deferred therapy
      in patients with clinically localized prostate cancer exceeded the estimated cost
      in age-matched controls by approximately US$88 million, equivalent to an average
      extra cost per patient of approximately US$18,500. Patients with clinically
      localized prostate cancer managed conservatively had a significantly higher
      morbidity than age-matched controls due to admissions associated with prostate
      cancer. In future comparisons of treatment strategies, morbidity following
      treatment and impact on quality of life have to be included when evaluating the
      outcome.

PMID- 12497172
TI  - Isolation and partial characterization of an epithelial cell line (RPE-F344) from
      the regenerating prostate of a normal adult male rat.
AB  - Normal prostate epithelial cells are difficult to propagate in vitro without
      experimental immortalization. The goal of this study was to isolate and
      characterize a propagable epithelial cell line from normal adult rat prostate.
      Enrichment of proliferation-competent cells was accomplished in vivo by
      initiating a single cycle of prostatic involution/regeneration. The RPE-F344 cell
      line was established from an androgen-deprived, involuted prostate four days
      after the initiation of regeneration by administration of testosterone. The cell
      line has been cultured in vitro for >50 passages, forms a uniform monolayer in
      culture, exhibits contact inhibition at confluence, and does not form colonies in
      soft agar. Immunocytochemical and RT-PCR analyses demonstrated that the RPE-F344
      cells express anti-apoptotic genes associated with cell survival, and several
      growth factor receptors important in prostate development and homeostasis. RPE
      F344 cells are p27kip1 negative, telomerase positive, and express high molecular
      weight cytokeratins specific for prostatic basal cells. They also express low
      levels of androgen receptor (AR) and prostatic acid phosphatase (PAP); features
      associated with secretory luminal epithelial cells. RPE-F344 cells are maintained
      in vitro without androgen supplementation, but addition of 15nM dihydrotesterone
      (DHT) to the culture media results in a significant but transient enhancement of
      cellular proliferation. Establishment of RPE-F344-like colonies from rat prostate
      is limited to the ventral and dorsal lobes of the prostate 2-4 days after
      initiation of regeneration, suggesting that RPE-F344 cells may originate from a
      stem cell-like compartment that is responsible for regenerative repopulation.

PMID- 12497173
TI  - Proteinchip(R) surface enhanced laser desorption/ionization (SELDI) mass
      spectrometry: a novel protein biochip technology for detection of prostate cancer
      biomarkers in complex protein mixtures.
AB  - Improving early detection, diagnosis, treatment monitoring and prognosis of
      cancer will require rapid and high throughput detection, identification, and
      measurement of multiple biomarkers. In this study, we demonstrate the versatility
      of the innovative SELDI ProteinChip(R) MS technology for the rapid, reproducible
      and simultaneous identification of four well-characterized prostate cancer
      associated (PCA) biomarkers, prostate specific antigen (free and complexed
      forms), prostate specific peptide, prostate acid phophatase and prostate specific
      membrane antigen in cell lysates, serum and seminal plasma. Proteins
      corresponding to the mass of these biomarkers could readily be captured and
      detected using either chemically defined or antibody coated ProteinChip(R)
      arrays. Several (yet to be identified) proteins were found upregulated in cell
      lysates of pure populations of PCA cells procured by laser capture
      microdissection (LCM) when compared with mass spectra of normal cell lysates.
      Coupling LCM with SELDI provides tremendous opportunities to discover and
      identify the signature proteins associated with each stage of tumor development.
      Collectively, these observations demonstrate the potential of SELDI for the
      discovery and simultaneous detection of and clinical assay development for PCA
      biomarkers in complex biological mixtures.

PMID- 12497174
TI  - A prospective randomized trial evaluating tissue effects of finasteride therapy
      in benign prostatic hyperplasia.
AB  - Finasteride is widely used for the treatment of benign prostatic hyperplasia
      (BPH). Its therapeutic efficacy is believed to be mediated through selective
      inhibition of prostatic 5alpha-reductase (type II). This prospective, controlled,
      randomized study examines various relationships between changes in tissue 5alpha
      reductase isozyme activity, epithelial proliferative index and morphology in men
      with BPH treated with finasteride for 6 months, and correlates these with
      clinical response. Thirty-one patients presenting with symptomatic bladder
      outflow obstruction were prospectively randomized to receive either finasteride
      or placebo (2:1) for 24 weeks. Of these, 27 men aged 55-80 y (median 69 y)
      completed the study, including 18 patients on treatment. Symptom score
      determination, uroflow and prostate volume were assessed at baseline and end of
      study. Prostatic tissue was obtained by ultrasound-guided needle biopsy at
      baseline and by transurethral resection (TURP) at end of study for biochemical
      and morphometric analysis. Epithelial proliferation was examined quantitatively
      in the resected tissue using MIB-1 antibody to Ki-67 and counting the percentage
      of positively staining cells. Type II 5alpha-reductase activity was strongly
      inhibited by finasteride in resected BPH tissue, with over 100-fold decrease in
      V(max) (P=0.001), whereas the type I isozyme was inhibited 5-fold (P=0.005).
      Selective inhibition of type II 5alpha-reductase was demonstrated in all treated
      patients. No significant difference in epithelial proliferation was observed
      between the finasteride and placebo groups. Epithelial proliferation was,
      however, greater in prostatic tissue with histological manifestation of
      inflammation (2.02% vs 0.89%, P=0.001). Positive correlation between the total
      epithelial volume and the ratio of transition zone volume/total prostate volume
      was observed in the placebo group (r=0.834), whereas there was no such
      correlation in men taking finasteride (r=-0.300), consistent with a reduction in
      epithelial content in the treatment group. Improvement in uroflow and reduction
      in prostatic volume in patients treated with finasteride did not reach
      statistical significance. This study shows that finasteride causes inhibition of
      5alpha-reductase activity in human BPH tissue with selectivity for the type II
      isozyme. In spite of this, no significant effects in epithelial proliferation or
      tissue morphology were demonstrated. The presence of inflammation was, however,
      associated with significantly greater proliferative activity. The power of this
      study was limited by the small number of recruited patients, and a larger study
      would be required for further investigation of morphological changes induced by
      finasteride in BPH tissue and their biochemical basis.

PMID- 12497175
TI  - Is invasive anesthetic monitoring necessary during radical prostatectomy?
AB  - The purpose of this study was to obtain objective information on the necessity of
      invasive anesthetic monitoring during radical prostatectomy. We reviewed
      retrospectively the charts of 257 patients undergoing radical prostatectomy on an
      established pathway which did not include the intraoperative use of an arterial
      line or central venous catheter. Outcome measures including intraoperative vital
      signs, cardiac arrhythmias, blood loss and fluid management were assessed. In
      particular, we sought to determine situations in which insertion of monitoring
      devices was required because of an unanticipated intraoperative event. The
      patient ages ranged from 40 to 75 y with a mean of 60.3 y. The mean estimated
      blood loss was 546.9 cm(3) (median 500 cm(3)). Thirty-eight patients had a
      measured intraoperative systolic blood pressure of <90 mmHg, but no hypotensive
      episodes required any treatment other than fluid administration. A single patient
      required pharmacologic therapy for hypertension. One patient received intravenous
      lidocaine because of premature ventricular contractions, but no other arrhythmias
      were observed. No patient required intraoperative insertion of an arterial line
      or central venous catheter. These data provide objective evidence for the
      abandonment of routine use of central venous catheters or arterial lines during
      radical prostatectomy. This avoids not only the expense of these maneuvers, but
      also the potential morbidity of unnecessary invasive medical procedures.

PMID- 12497176
TI  - Plasma steroid hormones, surgery for benign prostatic hyperplasia, and severe
      lower urinary tract symptoms.
AB  - Because benign prostatic hyperplasia (BPH) may be influenced by plasma steroid
      hormones, we examined their relation in the Health Professionals Follow-up Study.
      In 1993-1995, 18,000 cohort members provided blood. We selected as cases men who
      had had surgery for BPH (n=174) or who scored 20-35 points (n=126) on the
      American Urological Association index of severity of lower urinary tract
      symptoms. Cases were matched by age to men who scored</=3 points and without an
      enlarged prostate or elevated prostate-specific antigen. We estimated the odds
      ratio (OR) of BPH surgery and severe lower urinary tract symptoms for plasma
      testosterone (T), dihydrotestosterone (DHT), androstanediol glucuronide (AAG),
      estradiol (E2), and sex hormone binding globulin (SHBG) in multivariable
      conditional logistic regression models. Compared to the lowest tertiles, men in
      the middle (OR=1.42) and top (OR=1.78) tertiles of AAG were at increased risk for
      having either BPH surgery or severe lower urinary tract symptoms (P-trend=0.02).
      Men in the middle (OR=0.58) and top (OR=0.60) tertiles of E2 were at lower risk.
      T level was unrelated to surgery and symptoms. Our findings support opposing
      roles for DHT, reflected by its metabolite AAG, and E2 in the etiology of BPH.

PMID- 12497177
TI  - Malignant ascites as only manifestation of metastatic prostate cancer.
AB  - Prostate cancer is the most common malignancy in men in the US. Both at diagnosis
      and throughout the disease progression it can metastasize to multiple organs
      (bone and lymph being the most common). Effusions (either pleural or abdominal)
      are relatively uncommon, but usually occur as a result of soft tissue lesions.
      Herein we report on a patient with androgen independent prostate cancer and an
      elevated PSA with disease confined to ascites of the abdomen.

PMID- 12497180
TI  - Keyword Index To Volume 2.

PMID- 12497178
TI  - The British Prostate Group Autumn Meeting, 20-21 September 1999, Keble College,
      Oxford.

PMID- 12497181
TI  - Responding to the threat of bioterrorism: a microbial ecology perspective--the
      case of anthrax.
AB  - Anthrax is a disease of herbivores caused by the gram-positive bacterium Bacillus
      anthracis. It can affect cattle, sheep, swine, horses and various species of
      wildlife. The routes for the spread among wildlife are reviewed. There are three
      kinds of human anthrax--inhalation, cutaneous, and intestinal anthrax--which
      differ in their routes of infection and outcomes. In the United States,
      confirmation of cases is made by the isolation of B. anthracis and by biochemical
      tests. Vaccination is not recommended for the general public; civilians who
      should be vaccinated include those who, in their work places, come in contact
      with products potentially contaminated with B. anthracis spores, and people
      engaged in research or diagnostic activities. After September 11, 2001, there
      were bioterrorism anthrax attacks in the United States: anthrax-laced letters
      sent to multiple locations were the source of infectious B. anthracis. The US
      Postal Service issued recommendations to prevent the danger of hazardous exposure
      to the bacterium. B. anthracis spores can spread easily and persist for very long
      times, which makes decontamination of buildings very difficult. Early detection,
      rapid diagnosis, and well-coordinated public health response are the key to
      minimizing casualties. The US Government is seeking new ways to deter
      bioterrorism, including a tighter control of research on infectious agents, even
      though pathogens such as B. anthracis are widely spread in nature and easy to
      grow. It is necessary to define the boundary between defensive and offensive
      biological weapons research. Deterring bioterrorism should not restrict critical
      scientific research.

PMID- 12497182
TI  - Plant-microbe interactions and the new biotechnological methods of plant disease
      control.
AB  - Plants constitute an excellent ecosystem for microorganisms. The environmental
      conditions offered differ considerably between the highly variable aerial plant
      part and the more stable root system. Microbes interact with plant tissues and
      cells with different degrees of dependence. The most interesting from the
      microbial ecology point of view, however, are specific interactions developed by
      plant-beneficial (either non-symbiotic or symbiotic) and pathogenic
      microorganisms. Plants, like humans and other animals, also become sick, but they
      have evolved a sophisticated defense response against microbes, based on a
      combination of constitutive and inducible responses which can be localized or
      spread throughout plant organs and tissues. The response is mediated by several
      messenger molecules that activate pathogen-responsive genes coding for enzymes or
      antimicrobial compounds, and produces less sophisticated and specific compounds
      than immunoglobulins in animals. However, the response specifically detects
      intracellularly a type of protein of the pathogen based on a gene-for-gene
      interaction recognition system, triggering a biochemical attack and programmed
      cell death. Several implications for the management of plant diseases are derived
      from knowledge of the basis of the specificity of plant-bacteria interactions.
      New biotechnological products are currently being developed based on stimulation
      of the plant defense response, and on the use of plant-beneficial bacteria for
      biological control of plant diseases (biopesticides) and for plant growth
      promotion (biofertilizers).

PMID- 12497183
TI  - Microbial mats and the search for minimal ecosystems.
AB  - This article reviews some ecological concepts common to all kinds of ecosystems,
      describes the characteristics of microbial mats, and focuses on the description
      of the Ebro Delta microbial mats, to assess whether they fit the concept of a
      minimal ecosystem. First, microorganisms as components of ecosystems are
      considered, and some features of microbial life, including ubiquity, size and
      metabolism, genetic versatility, and strategies to overcome unfavorable
      conditions, are discussed. Models for ecosystems, regardless of their size, have
      the same basic components; tropical forests, multilayered planktonic microbial
      communities, and benthic microbial mats are analogous ecosystems at different
      scales. The structure--in terms of populations and communities--and ecophysiology
      of microbial mats are also discussed. The linear distribution of microbial
      populations along steep gradients of light and hydrogen sulfide allows for the
      simultaneous presence of different microbial populations. Defining the minimal
      ecosystem requirements necessary for the survival and proliferation of organisms
      is crucial in the search for extraterrestrial life and for establishing
      ecosystems beyond the Earth.

PMID- 12497184
TI  - Bioremediation of oil by marine microbial mats.
AB  - Cyanobacterial mats developing in oil-contaminated sabkhas along the African
      coasts of the Gulf of Suez and in the pristine Solar Lake, Sinai, were collected
      for laboratory studies. Samples of both mats showed efficient degradation of
      crude oil in the light, followed by development of an intense bloom of Phormidium
      spp. and Oscillatoria spp. Isolated cyanobacterial strains, however, did not
      degrade crude oil in axenic cultures. Strains of sulfate-reducing bacteria and
      aerobic heterotrophs were capable of degrading model compounds of aliphatic and
      aromatic hydrocarbons. Results indicate that degradation of oil was done
      primarily by aerobic heterotrophic bacteria. The oxygenic photosynthesis of oil
      insensitive cyanobacteria supplied the molecular oxygen for the efficient aerobic
      metabolism of organisms, such as Marinobacter sp. The diurnal shifts in
      environmental conditions at the mat surface, from highly oxic conditions in the
      light to anaerobic sulfide-rich habitat in the dark, may allow the combined
      aerobic and anaerobic degradation of crude oil at the mat surface. Hence, coastal
      cyanobacterial mats may be used for the degradation of coastline oil spills.
      Oxygen microelectrodes detected a significant inhibition of photosynthetic
      activity subsequent to oil addition. This prevailed for a few hours and then
      rapidly recovered. In addition, shifts in bacterial community structure following
      exposure to oil were determined by denaturing gradient gel electrophoresis of PCR
      amplified fractions of 16S rRNA from eubacteria, cyanobacteria and sulfate
      reducing bacteria. Since the mats used for the present study were obtained from
      oil-contaminated environments, they were believed to be preequilibrated for
      petroleum remediation. The mesocosm system at Eilat provided a unique opportunity
      to study petroleum degradation by mats formed under different salinities (up to
      21%). These mats, dominated by cyanobacteria, can serve as close analogues to the
      sabkhas contaminated during the Gulf War in Kuwait and Saudi Arabia.

PMID- 12497185
TI  - Studying marine microorganisms from space.
AB  - Microorganisms are but a few micrometers in diameter and are not visible to the
      naked eye. Yet, the large numbers of microorganisms present in the oceans and the
      global impact of their activities make it possible to observe them from space.
      Here a few examples of how microorganisms can be studied from satellites are
      presented. The first case is the best known: the main pigment used in
      photosynthesis (chlorophyll a) can be determined from satellites. These kinds of
      studies have contributed a tremendous amount of understanding about the
      distribution and dynamics of primary production in the oceans. Two other examples
      will concern analysis of heterotrophic prokaryotic production and estimates of
      dimethyl sulfide (DMS) concentration and flux to the atmosphere. These three
      processes are of fundamental importance for the functioning of the biosphere.
      Marine microbes carry out about half of the total primary production in the
      planet. A substantial fraction of the respiration in the oceans is due to the
      activity of heterotrophic prokaryotes. Finally, the flux of DMS to the atmosphere
      is believed to constitute one of the mechanisms by which the biota can regulate
      climate. The global implications of microbial processes in the oceans can only be
      addressed with the help of satellites.

PMID- 12497186
TI  - Microbial transformation of elements: the case of arsenic and selenium.
AB  - Microbial activity is responsible for the transformation of at least one third of
      the elements in the periodic table. These transformations are the result of
      assimilatory, dissimilatory, or detoxification processes and form the
      cornerstones of many biogeochemical cycles. Arsenic and selenium are two elements
      whose roles in microbial ecology have only recently been recognized. Known as
      "essential toxins", they are required in trace amounts for growth and metabolism
      but are toxic at elevated concentrations. Arsenic is used as an osmolite in some
      marine organisms while selenium is required as selenocysteine (i.e. the twenty
      first amino acid) or as a ligand to metal in some enzymes (e.g. FeNiSe
      hydrogenase). Arsenic resistance involves a small-molecular-weight arsenate
      reductase (ArsC). The use of arsenic and selenium oxyanions for energy is
      widespread in prokaryotes with representative organisms from the Crenarchaeota,
      thermophilic bacteria, low and high G+C gram-positive bacteria, and
      Proteobacteria. Recent studies have shown that both elements are actively cycled
      and play a significant role in carbon mineralization in certain environments. The
      occurrence of multiple mechanisms involving different enzymes for arsenic and
      selenium transformation indicates several different evolutionary pathways (e.g.
      convergence and lateral gene transfer) and underscores the environmental
      significance and selective impact in microbial evolution of these two elements.

PMID- 12497187
TI  - The biomineralization of magnetosomes in Magnetospirillum gryphiswaldense.
AB  - Magnetotactic bacteria (MTB) are major constituents of natural microbial
      communities in sediments and chemically stratified water columns. The ability of
      MTB to migrate along magnetic field lines is based on specific intracellular
      structures, the magnetosomes, which, in most MTB, are nanometer-sized, membrane
      bound magnetic particles consisting of the iron mineral magnetite (Fe(3)O(4)). A
      broad diversity of morphological forms has been found in various MTB. The unique
      characteristics of bacterial magnetosomes have attracted a broad
      interdisciplinary research interest. The magnetosome membrane (MM) in
      Magnetospirillum gryphiswaldense contains a number of specific Mam proteins.
      Several mam genes were analyzed and assigned to different genomic regions. Many
      of the Mam proteins are highly conserved in other MTB but display low sequence
      similarity to any proteins from nonmagnetic organisms.

PMID- 12497188
TI  - New approaches to the study of Antarctic lithobiontic microorganisms and their
      inorganic traces, and their application in the detection of life in Martian
      rocks.
AB  - Microbial life in the harsh conditions of Antarctica's cold desert may be
      considered an analogue of potential life on early Mars. In order to explore the
      development and survival of this epilithic and endolithic form of microbial life,
      our most sophisticated, state-of-the-art visualization technologies have to be
      used to their full potential. The study of any ecosystem requires a knowledge of
      its components and the processes that take place within it. If we are to
      understand the structure and function of each component of the microecosystems
      that inhabit lithic substrates, we need to be able to quantify and identify the
      microorganisms present in each lithobiontic ecological niche and to accurately
      characterize the mineralogical features of these hidden microhabitats. Once we
      have established the techniques that will allow us to observe and identify these
      microorganisms and mineral substrates in situ, and have confirmed the presence of
      water, the following questions can be addressed: How are the microorganisms
      organized in the fissures or cavities? Which microorganisms are present and how
      many are there? Additional questions that logically follow include: What are the
      existing water relationships in the microhabitat and what effects do the
      microorganisms have on the mineral composition? Mechanical and chemical changes
      in minerals and mineralization of microbial cells can give rise to physical
      and/or chemical traces (biomarkers) and to microbial fossil formation. In this
      report, we describe the detection of chains of magnetite within the Martian
      meteorite ALH84001, as an example of the potential use of SEM-BSE in the search
      for plausible traces of life on early Mars.

PMID- 12497189
TI  - Searching for life in the Universe: unconventional methods for an unconventional
      problem.
AB  - The search for life, on and off our planet, can be done by conventional methods
      with which we are all familiar. These methods are sensitive and specific, and are
      often capable of detecting even single cells. However, if the search broadens to
      include life that may be different (even subtly different) in composition, the
      methods and even the approach must be altered. Here we discuss the development of
      what we call non-earthcentric life detection--detecting life with methods that
      could detect life no matter what its form or composition. To develop these
      methods, we simply ask, can we define life in terms of its general properties and
      particularly those that can be measured and quantified? Taking such an approach
      we can search for life using physics and chemistry to ask questions about
      structure, chemical composition, thermodynamics, and kinetics. Structural
      complexity can be searched for using computer algorithms that recognize complex
      structures. Once identified, these structures can be examined for a variety of
      chemical traits, including elemental composition, chirality, and complex
      chemistry. A second approach involves defining our environment in terms of energy
      sources (i.e., reductants), and oxidants (e.g. what is available to eat and
      breathe), and then looking for areas in which such phenomena are inexplicably out
      of chemical equilibrium. These disequilibria, when found, can then be examined in
      detail for the presence of the structural and chemical complexity that presumably
      characterizes any living systems. By this approach, we move the search for life
      to one that should facilitate the detection of any earthly life it encountered,
      as well as any non-conventional life forms that have structure, complex
      chemistry, and live via some form of redox chemistry.

PMID- 12497190
TI  - A study of the early stage of Dysphagia in amyotrophic lateral sclerosis.
AB  - In amyotrophic lateral sclerosis (ALS) patients, dysphagia eventually occurs
      independent of time of onset. We studied dysphagia conditions in the early stage
      of ALS, principally at the oral phase. Videofluoroscopic and manometric studies
      were conducted on 11 patients (5 males and 6 females, age range = 47-82 years)
      who were diagnosed at our Neurology Clinic as having ALS. All patients were able
      to ingest orally. Swallowing scores on the ALS severity scale were from 10 to 5.
      In the oral phase of swallowing, abnormal movements of the anterior and/or
      posterior tongue were recognized in 8 cases. Dysphagia severity tended to be
      particularly influenced by dysfunction of the posterior tongue. Manometric
      studies were almost normal in all cases except one. These results suggested that
      the early stage of dysphagia in ALS was mainly caused by oral dysfunction, and
      the oral phase disorders began in some cases with a decreased function of bolus
      transport at the anterior part of the tongue, and in other cases with a
      deteriorated function of holding the bolus at the posterior part of the tongue.
      In conclusion, the tongue function of holding the bolus in the oral cavity mainly
      affects the severity of the early stage of dysphagia in ALS.

PMID- 12497191
TI  - Epiphrenic diverticulum: clinical and radiographic findings in 27 patients.
AB  - The purpose of our study was to reassess the clinical and radiographic findings
      in patients with epiphrenic diverticula. A search of our radiology files revealed
      27 patients with epiphrenic diverticula within 10 cm of the gastroesophageal
      junction. Medical records and radiographic reports and images were reviewed to
      determine the clinical and radiographic findings. Twenty-three patients had a
      solitary epiphrenic diverticulum, three had two diverticula, and one had three
      diverticula. The diverticula arose from the right side of the distal esophagus in
      19 patients and the left side in eight. The diverticula had a mean width of 4.4
      cm and a mean height of 3.7 cm. Other findings included prolonged retention of
      barium in the diverticula in 19 patients, preferential filling in 11, retained
      debris in 5, regurgitation of barium or debris in 5, compression of the esophagus
      in 5, pseudodiverticula formation in 3, and ulceration in 1. We found a
      significant correlation between the width of the diverticulum and preferential
      filling with barium. Twelve patients had abnormal esophageal motility, with
      diffuse esophageal spasm in two. Seventeen patients had symptoms attributable to
      the diverticulum (dysphagia in 11 and/or reflux symptoms in 12). We also found a
      significant correlation between the size or preferential filling of the
      diverticulum and the presence of symptoms. Conversely, we found no correlation
      between esophageal dysmotility and the presence of symptoms. Our experience
      suggests that the development of symptoms in patients with epiphrenic diverticula
      is more likely to be related to the morphologic features of the diverticula than
      to underlying esophageal motility disorders.

PMID- 12497192
TI  - Effects of mechanical, cold, gustatory, and combined stimulation to the human
      anterior faucial pillars.
AB  - Tactile-Thermal Application (TTA) is a therapy technique designed to enhance the
      swallowing response in persons with dysphagia. In this study, TTA was broken down
      into each component stimulus (i.e., Cold, Mechanical, Gustatory), and all
      combinations thereof, to study the effects of each condition on measurable
      parameters of the normal human swallow response. Using surface electromyography
      (EMG), latency to swallow-specific activity and duration of submental EMG
      activity were measured to examine the following questions: (1) Are there stimulus
      dependent differences in onset latencies and contraction durations of the
      submental muscle activity? (2) Which stimulus components are responsible for this
      response? (3) How long do the effects of stimulation last on the response? (4)
      Are there response differences according to age and gender? Between-subjects
      multivariate analysis of variance showed that the main effects for Treatment,
      Gender, and Age were significant. Latency to swallow-specific activity was
      significantly shorter following Mechanical + Cold + Gustatory condition compared
      to No Stimulation. The effect of stimulation on the swallow response lasted for
      only one swallow.

PMID- 12497193
TI  - Esophageal actinomycosis: a case report and review of the literature.
AB  - A 37-year-old African-American male with acquired immunodeficiency syndrome
      (AIDS) presented with recurrent chest pain. An upper gastrointestinal endoscopy
      had been performed two months previously and esophageal biopsy revealed extensive
      candidal infection with ulceration. He temporarily responded to fluconazole.
      Repeat biopsy revealed actinomyces and continued candidal infection. Review of
      the original biopsy also demonstrated actinomyces in addition to candida. After
      initial response to therapy with penicillin, he worsened on outpatient therapy
      and subsequently expired from progression of disease. Lack of compliance may have
      been contributary. To date, 8 patients with esophageal actinomycosis have been
      reported, five of whom had AIDS. Of the remaining three, none was otherwise
      immunocompromised. This is the first report of esophageal actinomycosis occurring
      as a superinfection of candidal ulceration. We also describe the findings and
      utility of thoracic CT in this condition and review the literature.

PMID- 12497194
TI  - Simultaneous modified barium swallow and blue dye tests: a determination of the
      accuracy of blue dye test aspiration findings.
AB  - The overall objective of this pilot study was to determine blue dye test
      reliability and validity for the identification of aspiration of secretions,
      food, and/or drink in 50 simultaneously administered blue dye (BDT) and modified
      barium swallow (MBS) tests of tracheostomized individuals. With the MBS as an
      objective test of aspiration, BDT sensitivity and specificity identifying
      aspiration were less than 80% and 62%, respectively. Certain tracheostomy tube
      conditions and food consistencies were associated with more accurate BDT
      aspiration results than others. Characteristics of the aspiration episodes,
      interpretation of the results, and needs for further research are discussed.

PMID- 12497195
TI  - The effects of cervical bracing upon swallowing in young, normal, healthy
      volunteers.
AB  - The purpose of this study was to evaluate radiographically the effects of
      cervical bracing upon swallowing thin liquids and solid food in normal adults
      under three cervical bracing conditions. This was a prospective, repeated
      measures design study. Seventeen healthy adult volunteers between the ages of 30
      and 50 were recruited from hospital staff. All subjects reported no previous
      history of swallowing difficulty or diseases that might affect swallowing.
      Subjects were radiographically observed swallowing thin liquids and solid food
      without cervical bracing and with three common cervical orthoses (Philadelphia
      collar, SOMI, and halo-vest brace). Order of bracing and type of bolus were
      randomized. Changes in swallowing function (point of initiation of swallow
      response, presence of pharyngeal residue, airway penetration, hyoid bone
      movement, diameter of oropharyngeal airway, and durational measurements) were
      analyzed by two independent raters. Eighty-two percent (14/17) of the subjects
      demonstrated radiographic changes under one or more of the bracing conditions.
      Forty-seven percent (8/17) of subjects demonstrated changes with point of
      initiation of the swallow response, 59% (10/17) demonstrated increased pharyngeal
      residue, and 23.5% (4/17) demonstrated changes with bolus flow with laryngeal
      penetration present. Aspiration did not occur under any of the bracing
      conditions. Changes noted in durational measurements for oral containment and
      total pharyngeal transit under the bracing conditions were not considered
      statistically significant. This study shows that cervical bracing does change
      swallowing physiology in normal healthy adults.

PMID- 12497196
TI  - Which commercial thickening agent do patients prefer?
AB  - If an objective swallowing assessment reveals that a particular patient is at
      risk of aspirating liquids into the trachea while drinking, speech and language
      therapists may prescribe a commercial "thickening agent" to mix into their
      drinks. If used correctly, these can help to reduce the risk of aspiration. This
      study compared the palatability of the five main thickening agents currently
      available on prescription in the UK. Eight patients, three therapists, and ten
      therapy students blind-tested three different nonalcoholic drink flavors,
      thickened with each of the five thickening agents. Their perceptual rating of
      each of these drinks was recorded using 5-point visual analog scales. Significant
      differences between the visual analog scale scores for each of the thickening
      agents was found, independent of the drink flavor. There was no significant
      difference between the patient and the therapist results. By offering the more
      palatable thickening agents in drink flavors that patients enjoy, we would hope
      to improve compliance with speech and language therapy recommendations, thereby
      reducing the patient's risk of aspiration.

PMID- 12497197
TI  - Interrater reliability of videofluoroscopic swallow evaluation.
AB  - The past two decades have brought an enormous widening of interest in and
      knowledge about swallowing disorders. The most frequently used technique for
      swallow evaluation is X-ray videofluoroscopy. Most interventions are based on
      this examination. Only a few studies assessing interobserver reliability of
      videofluoroscopy have been published. The aim of our study was to assess the
      interobserver reliability of videofluoroscopy for swallow evaluation. Fifty-one
      consecutive dysphagic patients referred for videofluoroscopy were entered into
      the study regardless of their underlying disorder. The first swallow (5 ml of a
      semisolid radio-opague contrast media) of each patient was assessed in the
      lateral projection by 9 independent, experienced observers from different
      international swallow centers. All studies were evaluated according to a
      standardized protocol sheet and the interobserver reliability was calculated. The
      interobserver reliabilities assessed as kappa coefficient for parameters of the
      oral and pharyngeal phase, for the temporal occurrence of penetration/aspiration,
      and for the location of bolus residue ranged from 0.01 to 0.56. High reliability
      with an intraclass coefficient of 0.80 was achieved only with the well defined
      penetration/aspiration score. Our study underlines the need for exact definitions
      of the parameters assessed by videofluoroscopy, in order to raise interobserver
      reliability. To date, only aspiration is evaluated with high reliability by
      videofluoroscopy, whereas the reliability of all other parameters of
      oropharyngeal swallow is poor.

PMID- 12497198
TI  - Role of the pharyngeal branch of the vagus nerve in laryngeal elevation and UES
      pressure during swallowing in rabbits.
AB  - Elevation of the larynx during swallowing plays an important role in protecting
      the laryngeal inlet and in the opening of the upper esophageal sphincter (UES).
      The thyrohyoid (TH) muscle is the most important muscle for laryngeal elevation,
      and it is thought to be innervated by the thyrohyoid branch. However, in
      preliminary studies we found that laryngeal elevation was severely disturbed
      after sectioning of the pharyngeal branch of the vagus nerve (X-ph). In the
      present study, we examined the role of the X-ph in laryngeal elevation and the
      contribution of this nerve to UES pressure. Ten male rabbits under anesthesia
      were used. Sectioning of the X-ph not only abolished the electromyographic
      activities of the TH and cricopharyngeus (CP) muscles, it also greatly reduced
      the maximal value of laryngeal elevation during swallowing. On the other hand,
      sectioning of the hypoglossal nerve, which contains the thyrohyoid branch,
      produced no appreciable change in the electromyographic activity of either muscle
      and it reduced the maximal value of the elevation only slightly. These results
      indicate that the X-ph innervates the TH and CP muscles and suggest that the X-ph
      plays an important role in elevating the larynx and in regulating the UES
      pressure in rabbits.

PMID- 12497200
TI  - The combi-targeting concept: a novel 3,3-disubstituted nitrosourea with EGFR
      tyrosine kinase inhibitory properties.
AB  - PURPOSE: To study the dual mechanism of action of FD137, a 3,3-disubstituted
      nitrosourea designed to block signaling mediated by the epidermal growth factor
      receptor (EGFR) on its own and to be hydrolyzed to an inhibitor of EGFR plus a
      DNA-damaging species. MATERIALS AND METHODS: HPLC was used to determine the half
      life (t(1/2)) of FD137 and to characterize its derived metabolite FD110. The dual
      mechanisms of DNA damaging and EGFR tyrosine kinase (TK) targeting were
      ascertained by the comet assay for DNA damage and by inmunodetection of
      phosphotyrosine in an ELISA and a whole-cell assay for EGFR-mediated signaling.
      The antiproliferative effects of the different drugs and their combinations were
      determined by the sulforhodamine B (SRB) assay. RESULTS: In contrast to BCNU,
      FD137 significantly blocked EGF-induced EGFR autophosphorylation (IC(50) 4 micro
      M) in the human solid tumor cell line A431. DNA damage induced by FD137 could
      only be observed after 24 h exposure, but the level of DNA damage remained 3.6
      fold lower than that induced by BCNU. This difference was rationalized by the 160
      fold greater stability of FD137 when compared with BCNU in serum-containing
      medium. Further, degradation of FD137 was accompanied by the slow release of
      FD110, an extremely potent inhibitor of EGFR TK [IC(50) (EGFR
      autophosphorylation) <0.3 micro M]. The complex properties of FD137 translated
      into a 55-fold greater antiproliferative activity than BCNU against the EGFR
      overexpressing A431 cells that coexpresses the O(6)-alkylguanine transferase
      (AGT). Depletion of AGT in these cells by the use of O(6)-benzylguanine (O(6)-BG)
      enhanced their sensitivity to BCNU by 8-fold, but only by 3-fold to FD137.
      CONCLUSIONS: The results overall suggest that the superior antiproliferative
      activity of FD137 when compared with BCNU may be associated with its ability to
      behave as a combination of many species with different mechanisms of action.
      However, the enhancement of its potency by O(6)-BG suggests that its
      antiproliferative effect was at least partially mitigated by AGT and perhaps it
      may be largely dominated by its signal transduction inhibitory component.

PMID- 12497201
TI  - Differential responses of EGFR-/AGT-expressing cells to the "combi-triazene"
      SMA41.
AB  - PURPOSE: Previous studies have demonstrated enhanced potency associated with the
      binary [DNA/epidermal growth factor receptor (EGFR)] targeting properties of
      SMA41 (a chimeric 3-(alkyl)-1,2,3-triazene linked to a 4-anilinoquinazoline
      backbone) in the A431 (epidermal carcinoma of the vulva) cell line. We now report
      on the dependence of its antiproliferative effects (e.g. DNA damage, cell
      survival) on the EGFR and the DNA repair protein O6-alkylguanine DNA
      alkyltransferase (AGT) contents of 12 solid tumor cell lines, two of which,
      NIH3T3 and NIH3T3 HER14 (engineered to overexpress EGFR), were isogenic. METHODS:
      Receptor type specificity was determined using ELISA for competitive binding, as
      well as growth factor-stimulation assays. DNA damage was studied using single
      cell microelectrophoresis (comet) assays, and levels of EGFR were determined by
      Western blotting. The effects of SMA41 on the cell cycle of NIH3T3 cells were
      investigated using univariate flow cytometry. RESULTS: Studies of receptor type
      specificity showed that SMA41: (a) preferentially inhibited the kinase activity
      of EGFR over those of Src, insulin receptor and protein kinase C (PKC, a
      serine/threonine kinase), (b) induced stronger inhibition of growth stimulated
      with EGF than of growth stimulated with platelet-derived growth factor (PDGF) or
      fetal bovine serum (FBS). Despite the EGFR specificity of SMA41, there was an
      absence of a linear correlation between the EGFR status of our solid tumor cell
      lines and levels of DNA damage induced by the alkylating component. Similarly,
      EGFR levels did not correlate with IC(50) values. The antiproliferative
      activities of SMA41 correlated more with the AGT status of these cells and
      paralleled those of the clinical triazene temozolomide (TEM). However, throughout
      the panel, tumor cell sensitivity to SMA41 was consistently stronger than to its
      closest analogue TEM. Experiments performed with the isogenic cells showed that
      SMA41 was capable of inducing twofold higher levels of DNA damage in the EGFR
      transfectant and delayed cell entry to G(2)/M in both cell types. When the cells
      were starved and growth-stimulated with FBS (conditions under which both cell
      types were growth-stimulated), in contrast to TEM, SMA41 and its hydrolytic
      metabolite SMA52 exhibited approximately nine- and threefold stronger inhibition
      of growth of the EGFR transfectant. CONCLUSIONS: These results suggest that, in
      addition to its ability to induce DNA damage and cell cycle perturbations, SMA41
      is capable of selectively targeting the cells with a growth advantage conferred
      by EGFR transfection. When compared with the monoalkyltriazene prodrug TEM, its
      potency may be further enhanced by its ability to hydrolyze to another signal
      transduction inhibitor (SMA52) plus a DNA alkylating agent that may further
      contribute to chemosensitivity. Thus, our new "combi-targeting" strategy may well
      represent a tandem approach to selectively blocking receptor tyrosine kinase
      mediated growth signaling while inducing significant levels of cytotoxic DNA
      lesions in refractory tumors.

PMID- 12497202
TI  - Evidence for the involvement of ET(B) receptors in ET-1-induced changes in blood
      flow to the rat breast tumor.
AB  - PURPOSE: Structure, growth, and function of the blood vessels in breast tumors
      are markedly different from those in normal breast tissue due to changes in the
      production of growth factors such as vascular endothelial growth factor (VEGF),
      vasoactive substances such as endothelin-1 (ET-1) and cytokines. The role of ET-1
      in breast tumor angiogenesis is not adequately understood. Studies have shown
      that the expression of proET-1, proET-3, and ET(B) receptors is increased in
      breast tumor. However, it is unclear whether there are any changes in ET-1
      induced vascular responses in breast tumor. Hence, in the present study we
      investigated systemic hemodynamics and regional circulatory effects of ET-1 in
      rats with breast tumors. METHODS: Female Sprague-Dawley rats weighing 180-200 g
      were divided into the following groups: (1) normal rats treated with saline (
      n=6), (2) tumor-bearing rats treated with methylnitrosourea (MNU) ( n=6), (3)
      normal rats treated with saline plus the specific ET(B) receptor antagonist BQ
      788 ( n=5), and (4) tumor-bearing rats treated with MNU plus BQ 788 ( n=5). Tumor
      development was monitored by regular palpation and measurement of tumor size.
      Once tumors had reached approximately 2-4 cm in diameter, the rats were
      anesthetized with urethane (1.5 g/kg i.p.) and their cardiovascular parameters
      were measured using a radioactive microsphere technique. Simultaneously, blood
      perfusion to the breast tissue was also measured using a laser Doppler technique.
      RESULTS: ET-1 produced a significant increase in mean arterial pressure in normal
      and tumor-bearing rats. Blood flow to the tumor tissue increased significantly in
      response to ET-1 as compared to breast tissue in normal rats. This response was
      accompanied by a concomitant decrease in vascular resistance in the tumor tissue.
      These results were confirmed by laser Doppler flowmetry, which showed a
      significant increase in blood perfusion to breast tumor compared to normal breast
      tissue. This increase in blood perfusion was attenuated by pretreatment with BQ
      788, suggesting an ET(B) receptor-mediated vasodilator action of ET-1 in rat
      breast tumor. CONCLUSIONS: The results indicate that ET-1 induced an increase in
      blood flow to breast tumor tissue mediated through ET(B) receptors.

PMID- 12497203
TI  - Clinical significance of thymidine phosphorylase and dihydropyrimidine
      dehydrogenase expression in transitional cell cancer.
AB  - PURPOSE: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine dehydrogenase
      (DPD) are thought to be key enzymes in the metabolic pathways of 5-fluorouracil
      (5-FU). Theoretically, tumors which have low DPD and/or high TdR-Pase expression
      should be 5-FU-sensitive. TdR-Pase also has angiogenic expression which aids
      tumor progression and metastasis. However, little is known concerning the
      relationship between DPD expression and clinical malignant potential, especially
      in urological cancer. MATERIALS AND METHODS: Transitional cell cancer (TCC)
      tissues were obtained from 50 patients, and TdR-Pase and DPD expression was
      measured by ELISA and radioenzyme assay, respectively. The sensitivity of 23 of
      the 50 specimens to 5-FU was assessed in a histoculture drug response assay
      (HDRA), an in vitro chemosensitivity test. RESULTS: TdR-Pase and DPD expression
      in TCC tissues was higher than in normal urothelial tissues. The expression of
      both TdR-Pase and DPD in TCC increased with histological grade and stage.
      Superficial bladder cancer patients who had undergone transurethral resection
      were divided into two groups, a recurrent and a nonrecurrent group. The
      expression of TdR-Pase and DPD was higher in the recurrent group than in the
      nonrecurrent group, but the differences were not significant. There was a
      significant inverse correlation between DPD expression and 5-FU sensitivity.
      However, TdR-Pase exhibited no correlation with 5-FU sensitivity. CONCLUSIONS:
      The expressions of both enzymes may be a good indicator of the malignant
      potential of TCC. Although DPD may be a good indicator of sensitivity of TCC to 5
      FU, TdR-Pase appeared not to regulate the sensitivity of TCC to 5-FU.

PMID- 12497204
TI  - Ototoxicity, nephrotoxicity and pharmacokinetics of cisplatin and its
      monohydrated complex in the guinea pig.
AB  - PURPOSE: To evaluate and compare the ototoxicity and nephrotoxicity of cisplatin
      and cis-diammineaquachloroplatinum(II) ion (monohydrated complex of cisplatin,
      MHC, formed in vivo by hydrolysis of cisplatin) after their separate
      administration to guinea pigs. METHODS: A dose of 4 mg/kg body weight of MHC was
      deemed suitable for the toxicity evaluation after dose titration.
      Electrophysiological hearing thresholds (auditory brainstem response, ABR),
      plasma creatinine and weight were measured in three groups of animals before and
      after receiving MHC 4 mg/kg (0.0141 mmol/kg), cisplatin 4.24 mg/kg (0.0141
      mmol/kg, i.e. equimolar dose) or cisplatin 8 mg/kg (0.0267 mmol/kg) as an i.v.
      bolus injection. Cisplatin and MHC were analysed using liquid chromatography with
      post-column derivatization. RESULTS: Administration of MHC 4 mg/kg caused a
      moderate ABR threshold shift, a significant increase in creatinine and a
      significant weight loss, changes similar to those seen after administration of
      cisplatin 8 mg/kg. Animals given cisplatin 4.24 mg/kg had a slight increase in
      creatinine, but had no ABR threshold shift and gained weight during the
      experiment. The pharmacokinetic parameters of cisplatin and MHC were estimated
      after administration of cisplatin 4.24 mg/kg and MHC 4 mg/kg. The area under the
      blood-ultrafiltrate concentration versus time curve (AUC) for cisplatin after
      administration of MHC 4 mg/kg was 23% (56+/-5.0 micro g.min.ml(-1)) (means+/-SD)
      of that after administration of cisplatin 4.24 mg/kg (240+/-25 micro g.min.ml(
      1)). The AUC for MHC after administration of cisplatin 4.24 mg/kg was 20% (30+/
      4.9 micro g.min.ml(-1)) of that after administration of MHC 4 mg/kg (149+/-26
      micro g.min.ml(-1)). CONCLUSIONS: MHC 4 mg/kg causes ototoxicity, nephrotoxicity
      and weight loss when administered to guinea pigs. The toxic effects were similar
      to those seen after administration of cisplatin 8 mg/kg and higher than those
      seen after administration of cisplatin 4.24 mg/kg.

PMID- 12497205
TI  - Marked potentiation of the antitumour activity of chemotherapeutic drugs by the
      antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
AB  - PURPOSE: To determine whether there is a therapeutic interaction between the
      antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and nine
      chemotherapy drugs against an early-passage mouse mammary tumour (MDAH-MCa-4),
      and to investigate the mechanism of any such interaction. METHODS AND RESULTS:
      Female C3H/HeN mice bearing intramuscular MDAH-MCa-4 tumours were injected
      intraperitoneally with DMXAA (80 micro mol/kg) or chemotherapy drug (at a range
      up to the maximum tolerated dose) alone, or coadministered. A small reduction in
      the dose of the chemotherapy drug was required in most cases, but the increase in
      antitumour effect was much greater than the increase in host toxicity (body
      weight loss). The therapeutic gain increased in the order 5-fluorouracil (no
      gain)<(etoposide, carboplatin, cyclophosphamide, doxorubicin,
      cisplatin)<(docetaxel, vincristine)<paclitaxel. The interaction with paclitaxel
      (31.6 micro mol/kg) was striking, with coadministration of DMXAA extending the
      median tumour growth delay from 0.3 to 80 days with three of seven animals cured.
      The interaction showed a broad timing of the optimum with similar activity when
      paclitaxel was administered 4 h before to 1 h after DMXAA: No therapeutic synergy
      was obtained when paclitaxel was combined with the antivascular agent
      combretastatin A4 phosphate (227 micro mol/kg), which induced only transient
      blood flow inhibition in this tumour, measured using the H33342 perfusion marker.
      Paclitaxel did not enhance the antivascular activity of DMXAA: Plasma and tumour
      concentrations of paclitaxel (and carboplatin), measured by LC-MS and ICP-MS
      respectively, were not elevated by combination with DMXAA: CONCLUSIONS: There was
      a dramatic therapeutic interaction between DMXAA and standard chemotherapy drugs,
      particularly paclitaxel, against the MDAH-MCa-4 tumour, which was not due to a
      pharmacokinetic interaction or potentiation of antivascular activity. It is
      suggested that the major mechanism of synergy is killing of cells by DMXAA in
      poorly perfused regions of tumours that are inaccessible to chemotherapy drugs.

PMID- 12497206
TI  - Delivery of interleukin-12 in gelatin hydrogels effectively suppresses
      development of transplanted colonal carcinoma in mice.
AB  - PURPOSE: The sustained effects of interleukin-12 (IL-12) incorporated in
      biodegradable hydrogel on the development of transplanted colon carcinoma were
      investigated in C57BC/6 N mice. METHODS: IL-12 was given to the animals
      incorporated in gelatin hydrogels (GH) which allow its gradual release. As the
      control administration, IL-12 was given via two subcutaneous injections at an
      interval of 6 days. Growth of the tumors was evaluated in terms of volume.
      RESULTS: When IL-12 at 500 ng/animal was administered in GH, the tumor volume was
      decreased 9 and 12 days after administration, and the response was dose dependent
      in the range 0-500 ng/animal. The effect of IL-12 was stronger in mice treated
      with GH than in mice treated by subcutaneous injection at the same dose (i.e. 250
      ng/animal twice at an interval of 6 days). Feeding behavior and the post-mortem
      wet weight of several visceral organs were unchanged after IL-12 administration.
      Serum parameters relative to the liver, heart and kidneys were unaffected by IL
      12 treatment. No noticeable toxicity was detected when the dose of IL-12 in GH
      was increased to 1000 ng/animal. CONCLUSIONS: The results suggest that IL-12 is
      effective in suppressing the growth of colon carcinoma, and that delivery of this
      agent in GH is efficient in the treatment of carcinoma.

PMID- 12497207
TI  - A study to evaluate the pharmacokinetics of oral 5-fluorouracil and eniluracil
      after concurrent administration to patients with refractory solid tumours and
      varying degrees of renal impairment (FUMA1005).
AB  - BACKGROUND: Eniluracil is an inactivator of dihydropyrimidine dehydrogenase, the
      first enzyme in the catabolic pathway of 5-fluorouracil (5-FU). Concurrent
      administration of oral eniluracil with oral 5-FU not only increases the
      bioavailability of 5-FU, owing to elimination of first-pass metabolism, but can
      change the route of elimination of 5-FU from hepatic metabolism to renal
      excretion. An open-label study was performed to determine the effect of renal
      impairment on the pharmacokinetics of 5-FU in the presence of eniluracil.
      METHODS: Enrolled in the study were 17 patients with refractory solid tumours
      (Karnofsky performance status >/=70%; age 31-74 years; 12 male, 5 female). The
      patients were separated into two groups based upon creatinine clearance (CLCr):
      group A had "normal" renal function arbitrarily defined as CLCr >/=50 ml/min (
      n=8), and group B had moderate renal impairment, i.e. CLCr <50 ml/min ( n=9).
      Treatment was separated into test and treatment periods. During the test period
      all patients received eniluracil 50 mg orally on days 1-3 and 5-FU 10 mg/m(2)
      together with pharmacokinetic measurements. During the treatment period, all
      patients received eniluracil 50 mg orally on days 1-7 with 5-FU at a standard
      dose of 20 mg/m(2) for those in group A or a dose individualized according to the
      pharmacokinetic parameters in the test period for those in group B. RESULTS: The
      clearance of both eniluracil and 5-FU was decreased in patients with renal
      impairment compared to those with normal renal function. A linear relationship
      was observed between 5-FU CL/F and CLCr in patients with renal impairment, but
      not in those with normal renal function. 5-FU dose modification, on the basis of
      the test dose pharmacokinetic data for the patients with renal function
      impairment, accurately resulted in drug exposure in the potentially therapeutic
      range. Toxicity was not increased. CONCLUSIONS: Eniluracil increases the oral
      bioavailability of 5-FU and results in a switch from hepatic metabolism to renal
      elimination. A standard dose of this combination can be administered safely to
      patients with CLCr >50 ml/min. The combination can also be given to patients with
      renal impairment using a test dose and pharmacokinetic measurements to predict
      the appropriate dose of 5-FU. It is expected that sufficient information will be
      available from this and other studies to allow accurate prediction of the
      appropriate 5-FU dose modifications required in patients with renal impairment.

PMID- 12497208
TI  - Biological properties of jatrophane polyesters, new microtubule-interacting
      agents.
AB  - PURPOSE: The biological activities of macrocyclic jatrophane polyesters 1-3 from
      the Sardinian endemism Euphorbia semiperfoliata Viv. have not been evaluated in
      depth. We investigated the microtubule-interacting and antiproliferative
      activities of these drugs and the molecular mechanisms underlying their effects.
      METHODS: We tested jatrophanes for their interaction with purified bovine brain
      tubulin by an in vitro polymerization assay and by electron microscopy. At a
      cellular level, the effects of jatrophanes on microtubular architecture, nuclear
      morphology, cell viability, cell cycle perturbations, and p53 and Raf-1/Bcl-2
      involvement were investigated. RESULTS: Jatrophanes exhibited microtubule
      interacting activity. They stimulated purified tubulin assembly in vitro, and
      induced paclitaxel-like microtubules, as revealed by electron microscopy. In the
      cells, rearrangement of microtubule architecture was in contrast to the bundling
      produced by paclitaxel. Jatrophanes inhibited the growth of some human cancer
      cell lines without inducing cell cycle arrest in the G2/M phase. Moreover, they
      influenced p53 expression and Raf-1/Bcl-2 activation. CONCLUSIONS: Despite their
      structural difference from paclitaxel and other microtubule-interacting agents,
      jatrophanes may represent a new type of tubulin binder.

PMID- 12497209
TI  - Suppressive effect of Astragalus membranaceus Bunge on chemical
      hepatocarcinogenesis in rats.
AB  - Astragalus membranaceus (AM) has been widely used for treating liver diseases in
      traditional Chinese medicine. Experimental evidence indicates that it has
      antitumor potential. In this study, the effect of AM on hepatocarcinogenesis
      induced by diethylnitrosamine (DEN), two-thirds partial hepatectomy, and 2
      acetylaminofluorene (2-AAF) (DEN-PH-AAF) was evaluated using glutathione S
      transferase placenta form (GST-P) as marker. First, rats were injected
      intraperitoneally (i.p.) with DEN (200 mg/kg in saline), a two-thirds partial
      hepatectomy was carried out 2 weeks later, and the rats were then placed on a
      basal diet containing 0.02% AAF from week 3 to week 8 to induce
      hepatocarcinogenesis. The rats were given AM (90 mg/kg or 180 mg/kg body weight)
      by gavage from week 3 to week 8 (treatment groups). The formation of GST-P
      positive foci and the expression of GST-P protein and mRNA caused by DEN-PH-AAF
      were reduced in the treatment groups, which clearly suggests that AM is effective
      in delaying DEN-PH-AAF-induced hepatocarcinogenesis.

PMID- 12497210
TI  - Pilot study of pegylated interferon-alpha 2b in patients with essential
      thrombocythemia.
AB  - PURPOSE: Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce
      platelet counts, and reduce the bone marrow megakaryocyte mass in patients with
      essential thrombocythemia (ET). A semisynthetic protein-polymer conjugate of IFN
      alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducted
      a pilot study of Peg-IFN2b in patients with ET. PATIENTS AND METHODS: Patients
      with a history of persistent (greater than 2 months) platelet counts >600 x
      10(9)/l, with hyperplasia of bone marrow megakaryocytes in the absence of an
      alternate identifiable cause of thrombocytosis were eligible. Patients were
      required to have either thrombohemorrhagic signs and/or symptoms if previously
      untreated; persistence of thrombohemorrhagic signs and/or symptoms if receiving
      anagrelide, IFN-alpha, or hydroxyurea; or intolerance to anagrelide, IFN-alpha,
      or hydroxyurea. The initial PEG-IFN2b dose was from 1.5 to 4.5 micro g/kg per
      week subcutaneously with subsequent dose adjustments as indicated by response and
      adverse events. RESULTS: Eleven patients (nine female, median age 54 years, range
      26-69 years) were treated. PEG-IFN2b rapidly controlled platelet counts and
      resolved symptoms in all patients. The median duration of PEG-IFN2b therapy on
      study was 9 months (range 4-17 months). No patient had signs or symptoms of
      thrombosis or hemorrhage while on study. After 2 months of therapy, 10 patients
      (91%) were in complete remission, and 11 (100%) after 4 months. One patient
      discontinued therapy at 4 months because of persistent grade 3 fatigue and a
      second at 5 months because of anxiety and depression. CONCLUSION: PEG-IFN2b has
      significant activity in patients with ET. Long-term follow-up of a larger cohort
      of patients is needed to define its role in this disease.

PMID- 12497211
TI  - Pilot study of Mylotarg, idarubicin and cytarabine combination regimen in
      patients with primary resistant or relapsed acute myeloid leukemia.
AB  - PURPOSE: Mylotarg has moderate activity as a single agent in patients with CD33
      positive refractory or relapsed acute myelogenous leukemia (AML). A combination
      of an anthracycline and cytarabine (ara-C) is the core of most AML induction
      regimens. We conducted a pilot study of Mylotarg combined with idarubicin and ara
      C in patients with refractory or relapsed AML. METHODS: Mylotarg was administered
      at 6 mg/m(2) intravenously on days 1 and 15, idarubicin 12 mg/m(2) daily on days
      2 through 4, and ara-C at 1.5 g/m(2) daily on days 2 through 5 (MIA) RESULTS: Of
      14 patients were treated, 4 (29%) had primary resistant AML, and 10 (71%)
      relapsed AML. The median age of the patients was 61 years (range 34-74 years).
      MIA induced complete remission (CR) in three patients (21%) and CR with
      incomplete platelet recovery (CRp) in three patients (21%). The median survival
      was 8 weeks (range 2-64 weeks), and the median failure-free survival of CR
      patients was 27 weeks (range 11-64 weeks). All patients developed grade 3/4
      myelosuppression - severe sepsis occurred in ten patients (71%). Other grade 3/4
      nonhematologic toxicities included hepatic transaminitis, oral mucositis, and
      diarrhea. Two patients (14%) developed hepatic venoocclusive disease (VOD).
      CONCLUSIONS: The addition of Mylotarg to idarubicin and ara-C is feasible. MIA
      has significant activity in patients with refractory AML. Hepatotoxicity and VOD
      are significant toxicities of Mylotarg-based combinations.

PMID- 12497212
TI  - Sensitivity to cisplatin treatment of human K1 thyroid carcinoma cell lines with
      altered p53 function.
AB  - AIM: p53 is the most frequently altered gene in human cancer. It was expected to
      be the principle marker for chemo/radiosensitivity, resistance, tumor recurrence
      and ultimate survival, but is no longer considered a universal prognostic factor.
      Different alterations in the p53 gene have led to conflicting results depending
      on cell/tissue specificities and on radiation and drug specificities. METHODS: We
      evaluated the properties of isogenic and isophenotypic cell lines from the K1
      papillary thyroid carcinoma in which p53 function was disrupted either by
      mutation (expression of dominant-negative p53, 143(ala)) or by inactivation
      (expression of human papilloma virus protein HPV16 E6). Their proliferation,
      their propensity to trigger apoptosis and their survival were analyzed after
      treatment with cisplatin (CDDP). RESULTS: Only K1 lines with wild-type p53 had
      significantly accumulated apoptotic bodies 72 h after treatment. Despite their
      incapacity to trigger apoptosis in response to CDDP treatment, the survival of K1
      cell lines in which p53 expression was altered was not significantly different
      from the survival of K1 cell lines expressing wild-type p53. In addition, the
      order of magnitude of resistance of K1 cells in which p53 was mutated was similar
      to that in which p53 was totally inactivated, although the pathways involved may
      be different. CONCLUSIONS: These results show that the means by which p53
      expression is disrupted and the consequence on downstream pathways regulated by
      p53 deserve to be considered in order to elucidate some apparently conflicting
      responses of this gene.

PMID- 12497213
TI  - Relationship between the descending branch of the inferior gluteal artery and the
      posterior femoral cutaneous nerve applicable to flap surgery.
AB  - Flap surgery in the distal part of the gluteal region has to deal with a lack of
      detailed descriptions of the inferior gluteal artery and the posterior femoral
      cutaneous nerve. The existing papers are mainly clinical studies, based on low
      numbers of observations. Our study includes 118 cadaveric gluteal regions. The
      descending branch was present in 91% and gave rise to a cutaneous branch. When
      the descending branch was absent, this cutaneous branch came from the medial or
      lateral femoral circumflex artery or as a perforator of the deep artery of the
      thigh. The posterior femoral cutaneous nerve was found in a common sheath of
      connective tissue with the descending branch of the inferior gluteal artery in
      72% of cases. Nerve loops around the vessel are present in 29%. Our results show
      that a cutaneous or fasciocutaneous flap, either local or free, in this region
      can be reliably lifted on a cutaneous branch of the descending branch of the
      inferior gluteal artery without loss of sensitivity. However, the close
      relationship of the artery and nerve limits the arc of rotation in the case of a
      local flap.

PMID- 12497214
TI  - Facial subdermal vascular network flap: anatomic study and clinical application.
AB  - Despite the numerous flaps for facial reconstruction that have been described,
      the search for the ideal flap with good color matching and minimal donor-site
      morbidity continues. In the past 3 years we have repaired 13 facial defects with
      success using the lateral genicervical flap - a type of facial subdermal vascular
      network flap (SVNF) - with a pedicle located on the preauricular region. An
      anatomic study of the facial SVNF, including blood supply and vascular
      distribution of the face and anatomic characteristics of facial vessels, based on
      14 cadaver dissections, was carried out. The blood supply of the facial skin
      basically originated from the branches of the facial, superficial temporal and
      infraorbital arteries. The lateral genicervical skin was supplied basically by
      the branches of the facial, superficial temporal and occipital arteries, but also
      by the terminal branches of the superior thyroid artery. The branches diverging
      from these arteries became superficial and formed a subcutaneous arterial
      network. The arterioles from the network went to the corium layer and formed a
      subdermal arterial network whose arterioles anastomosed with each other in a
      honeycomb-like structure. The vascular distribution presented certain directivity
      on different areas. The blood supply of the pedicle originated from the subdermal
      vascular network formed by the perforator branches of these arteries. The
      arterioles from the facial and superficial temporal arteries anastomosed in the
      lateral genicervical region. From the anatomic study, we think that the viability
      of the facial SVNF depends basically on the subdermal vascular network formed by
      the perforator branches of the pedicle, and that the anastomoses between the
      facial and superficial temporal arteries provide a solid anatomic basis to the
      lateral genicervical flap. The clinical data also indicated that this flap is a
      useful alternative for facial, especially superficial temporal, defects. But the
      directivity must be taken into account in its clinical application.

PMID- 12497215
TI  - Variations in collateral contributions to the blood supply to the sternum.
AB  - The blood supply of the sternum plays a major role in healing of the sternum
      after sternotomy. The sternal blood supply is derived mainly from the medial
      horizontal branches of the internal thoracic artery (ITA). The ITA is usually
      described as giving off sternal, anterior intercostal and perforating branches
      supplying their respective areas. The aim of the present study was to describe
      variations in the arterial branching pattern of collateral contributions to the
      sternum. The study was conducted on 30 fresh specimens of anterior thoracic wall
      in which cellulose acetate butyrate was injected into the ITA. The branches of
      the ITA in the first to sixth intercostal spaces were dissected and any
      additional artery supplying the sternum in each intercostal space was observed.
      In the present study, the ITA gave off non-collateral branches - sternal,
      anterior intercostal and perforating. The ITA was also found to have branches
      which divided into two to supply two destinations which could establish
      collateral flow to the sternum: (1). A sterno-intercostal branch (1-12 mm in
      length) divided and diverged in a Y or T shape. The medial limb supplied the
      sternum and the lateral limb supplied the adjoining thoracic wall, anastomosing
      with the terminal part of the posterior intercostal artery. (2). A sterno
      perforating branch supplied the sternum either anteriorly or posteriorly before
      perforating and supplying the pectoral region and anastomosing with the
      thoracoacromial artery. This study reinforces the practice of ligating branches
      of the ITA close to its trunk as they have the potential to develop collateral
      blood supply. In the present study the posterior intercostal artery was at times
      found to supply the sternum directly or via its collateral branch and was named
      the persistent posterior intercostal artery.

PMID- 12497216
TI  - Microvascularization of the female urethra in fetuses, neonates and infants.
AB  - The microvascularization of the female urethra was studied in fetuses, neonates
      and infants by injection of agarized China ink into the circulation. The purpose
      of this study was to specify the angioarchitecture of each tunic and their
      specific drainage. The disposition of the microvascularization of the urethra is
      superimposed on the orientation of the fibers of the muscular tunic. The
      orientation of the veins of the sub-mucous tunic is longitudinal and not
      plexiform.

PMID- 12497217
TI  - A study on the sectional anatomy of the oculomotor nerve and its related blood
      vessels with plastination and MRI.
AB  - To obtain normal images and sectional anatomical data of the oculomotor nerve and
      its related arteries, the optimal angles and the length of intracisternal segment
      of the oculomotor nerve were measured on MPR images. Meanwhile, the relationships
      between the nerve and the basilar, posterior cerebral, superior cerebellar and
      posterior communicating arteries were observed from plastination slices, original
      images, MPR and MIP images. MRI revealed similar results to the plastination
      sections. The intracisternal segment of oculomotor nerve formed an angle with the
      posterior plane of the brainstem. The angle was significantly smaller in
      individuals under 10 and over 50 years old ( P<0.05), and there was no marked
      difference in the angle between the oculomotor nerve and the median sagittal
      plane among the different groups ( P>0.05). Shift of the basilar artery was more
      likely to be found in aged individuals. Most of the posterior cerebral and
      superior cerebellar arteries were close to the nerve, and a few of them seemed to
      compress it; for the posterior communicating artery, only the embryonic type was
      close to or seemed to compress the nerve. MRI is an accurate imaging technique
      for determination of the relationship of the oculomotor nerve to its related
      arteries.

PMID- 12497218
TI  - Morphology and some biomechanical properties of human liver and spleen.
AB  - The aim of the study was an experimental determination of some morphological and
      mechanical properties of human liver and spleen (amount of collagen in organ
      capsules, their critical tension and density), followed by a definition of the
      threshold of critical acceleration, above which the organs can be injured during
      a car crash. Experiments were done on 33 fresh cadavers (18 males, 15 females;
      age 3 months to 88 years), and completed by sled tests on dummies testing the
      loads of both hypochondrial regions protected by air bags and/or seat belts.
      Results obtained were the following: (1). liver: capsule collagen 14-35%,
      critical tension 0.066-0.386 MPa, density 0.92-1.19 g/ml, critical acceleration
      48-155 g; (2). spleen: capsule collagen 1.8-24.4%, critical tension 0.022-0.652
      MPa, density 0.85-1.25 g/ml, critical acceleration 33-149 g. Loads of both
      hypochondrial regions measured on dummies during a predefined sled test were 34
      67 g. Results obtained were evaluated qualitatively and discussed from the point
      of view of their possible use in future passive safety engineering and design
      calculations.

PMID- 12497219
TI  - Anatomical study of the length of the human intestine.
AB  - Although preoperative assessment of the length of the intestine may be of
      interest to avoid postoperative consequences of large intestinal resection,
      measurements of the intestine are quite rare and results variable in the
      literature. This anatomical study aimed to assess the length of the different
      intestinal segments, their variation and their correlation with sex, age, weight
      and height. Two hundred non-fixed adult cadavers (100 men, 100 women) who
      willingly gave their bodies for scientific purposes were studied. The post mortem
      average length of the whole intestine was 795.5+/-129 cm and was significantly
      longer in men and in young subjects. It was correlated with the subject's weight
      but not height. Multivariate analysis demonstrated that the factor showing the
      strongest correlation with intestinal length was body weight. This latter
      parameter may be useful in the preoperative assessment of intestinal length.

PMID- 12497220
TI  - Biometry of the radial head: biomechanical implications in pronation and
      supination.
AB  - The aim of this study was to perform biometry of the proximal extremity of the
      radius and to characterize the shape of the radial head. Knowledge of the size
      and shape of the radial head is necessary for the creation of a radial head
      prosthesis that is anatomically and biomechanically correct. Twenty-seven
      measurements, focused on the proximal extremity, were done on 96 radii. The shape
      of the radial head was determined by the difference between the maximum diameter
      and the minimum diameter. We considered the shape to be circular when the
      difference was less than 1 mm, and elliptical when the difference was greater
      than 1 mm. The shape of the radial head was compared with the neck/diaphysis
      angle. Fifty-seven percent of radial heads were elliptical and 43% were circular.
      When the head was elliptical the maximum diameter was 22 mm +/-2.9 and the
      minimum diameter was 20 mm +/-2.8 ( P<0.001). When the head was circular the
      maximum diameter was 21.2 mm +/-2.4 and the minimum diameter was 20.4 mm +/-2.4 (
      P<0.14). The angle between the neck and the diaphysis varied with regard to the
      shape of the radial head. It was 166.75 degrees +/-3 for the circular heads and
      168.62 degrees +/-3.2 for the elliptical heads ( P<0.01). The biomechanics of the
      circular shape and the elliptical shape are different, involving an adaptation of
      the angle between the neck and the radial diaphysis. This difference must be
      taken in consideration in the design of a radial head prosthesis.

PMID- 12497221
TI  - The synovial fold of the humeroradial joint: anatomical and histological
      features, and clinical relevance in lateral epicondylalgia of the elbow.
AB  - The synovial fold of the humeroradial joint is known, and sometimes considered as
      a meniscus that could be injured by chronic repeated trauma related to pronation
      and supination. The aims of this study were to determine the gross anatomy and
      histological structure of this fold, and to clarify its participation in the
      painful lateral syndromes of the elbow. Fifty elbows from adult cadavers were
      dissected. The capsule of the humeroradial part of the elbow joint was resected
      with the annular ligament. The presence of a synovial fold, and its location
      relative to the cranial edge of the annular ligament divided into five sectors
      (ventral, ventrolateral, lateral, laterodorsal and dorsal) were noted;
      morphological parameters such as thickness, width and length were measured. The
      histological examination determined the structure of the folds. Five synovial
      folds were resected during surgery for epicondylalgia in five patients who
      suffered from pain precisely at the level of the joint between the capitulum and
      the fovea radialis, and were also examined. A fold was present in 43 cases, and
      in two cases two folds were seen at the deep side of the junction between the
      capsule and the annular ligament. The most frequent positions were: dorsal (
      n=11), laterodorsal and dorsal ( n=6;), lateral to dorsal ( n=5), lateral ( n=5),
      ventral ( n=4) and circular ( n=4). The mean length was 21.4 mm (range from 9-51
      mm). The mean width was 2.9 mm (range 1-10 mm), and the mean maximal thickness
      1.7 mm (range 1-4 mm). The histological study showed two types of folds: a rigid
      structure, with oriented fibrous tissue, triangular with a peripheral capsular
      base, covered on its two sides and along the free edge by a synovial layer; and a
      pliable structure, formed of two synovial layers that surrounded a thin fatty
      tissue, with a villous appearance of the free edge. No fibromyxoid structure, as
      in a real meniscus, was observed. Some nerve fibers were seen in the folds. The
      five folds resected in operated patients were hypertrophic, and showed an
      increased number of nerve fibers, along the capsule but also close to the
      synovial layer. Some painful syndromes of the lateral side of the elbow are not
      related to tendinitis or to posterior interosseous nerve compression, but have an
      intra-articular origin. This study showed that the synovial fold is not a
      meniscus, and may be involved in the etiology of lateral epicondylalgia.

PMID- 12497222
TI  - The anatomical relationship of the aortic bifurcation to the lumbar vertebrae: a
      MRI study.
AB  - The objective of this study was to determine the level of the aortic bifurcation
      in relation to the lumbar spine by MRI and the effect of lumbosacral anomalies on
      the aortic bifurcation. A prospective study of 441 patients was performed.
      Sagittal MR images of the entire spine were obtained along with the standard
      protocol for imaging of the lumbar spine. The vertebrae were counted caudally
      from C2 instead of cranially from the presumed L5 vertebra. The aortic
      bifurcation in relation to the lumbar vertebrae was determined. The aorta
      bifurcated at the L4 vertebral body in 67% of cases. In patients with
      sacralization of L5 the aortic bifurcation was at the L3 vertebral body in 59%.
      In those patients with lumbarization of S1 the aorta bifurcated at the level of
      the L4 vertebral body in 40% and at the L4/5 disc space in 33%. There was no
      demographic variation of the aortic bifurcation in relation to age or sex. The
      aorta bifurcated at L4 in two-thirds of cases and was variably located in the
      remaining third. The stability of this as a landmark is disturbed by the
      significant high incidence of lumbosacral transitional segments.

PMID- 12497223
TI  - Identification of the anterior and posterior portions of the lateral pedicle
      cortex by roentgenograms in pedicle screw fixation.
AB  - Forty lumbar pedicles and pedicle screws in four cadavers were used to identify
      the anterior and posterior portions of the lumbar pedicle cortex by
      roentgenograms in order to evaluate the penetration of the pedicle cortex by
      pedicle screws intraoperatively. Firstly, the transverse pedicle angles were
      measured on roentgenograms. Three roentgenograms were taken on each pedicle in
      three different directions: (1). medial to the pedicle axis; (2). pedicle axis;
      (3). lateral to the pedicle axis. They revealed that the anterior portion of the
      lateral pedicle cortex was demonstrated by the pedicle lateral outline on the
      roentgenogram medial to the pedicle axis, and the posterior portion by the
      pedicle lateral outline on the roentgenogram lateral to the pedicle axis. Wire
      markers were used to confirm these data. Finally, anterior and/or posterior
      penetrations on the lateral pedicle cortex in pedicle screw fixation were studied
      by roentgenograms in these cadavers and showed that anterior penetration of
      lateral cortex was demonstrated by the view medial to the pedicle axis, and
      posterior penetration by the view lateral to the pedicle axis. It is concluded
      that projections medical and lateral to the pedicle axis are necessary to
      identify lateral screw penetration intraoperatively when X-ray checking is used.

PMID- 12497224
TI  - Computed tomography of a cyclotocephalic neonate.
AB  - Cyclotocephaly is a very rare malformative lethal condition which associates
      otocephaly (extreme hypoplasia of the mandibular arch with agnathia) and cyclopy
      with proboscis. The head of a cyclotocephalic neonate from our Museum of Anatomy
      and Embryology was examined using computed tomography (CT). Cutaneous and osseous
      three-dimensional reformations were performed. Severe bony malformations were
      observed. A single orbital cavity was surrounded by a cartilaginous proboscis and
      a median fusion of maxillae, temporal and zygomatic bones. The single orbital
      cavity contained both paramedial eyeballs (synophthalmia). The external auditory
      meati and the ear pinnae were also parasagittal. No oral cavity and mandible were
      observed. Despite the poor conservation state of the brain, lobar
      holoprosencephaly was suspected. The mesencephalon and pituitary gland were
      absent. This exercise could lead to optimizing ultrasonographic prenatal
      diagnosis.

PMID- 12497225
TI  - Agenesis of sphenoid sinuses.
AB  - We present a 50-year-old woman with agenesis of the sphenoid sinuses. She was
      referred for evaluation of the aeration status of the sphenoid sinus and related
      nasal structures before endoscopic transsphenoidal hypophysectomy for pituitary
      microadenoma. Axial and coronal computed tomography (CT) scans revealed absence
      of the sphenoid sinuses and the right posterior ethmoidal cell. Agenesis of
      sphenoid sinuses documented using CT scans is uncommon. One case with a history
      of Hand-Schuller-Christian disease has been reported in the English language
      literature. In the case reported here agenesis of the sphenoid sinuses was not
      accompanied by craniofacial anomaly or skeletal disease.

PMID- 12497226
TI  - Celiac trunk compression by arcuate ligament and living-related liver
      transplantation: a two-step strategy for flow-induced enlargement of donor
      hepatic artery.
AB  - The median arcuate ligament is a tendinous arch joining the two medial borders of
      the diaphragm crura together. In 10-50% of subjects it is responsible for
      significant angiographic celiac trunk compression. In severe cases, a decrease in
      hepatic arterial blood flow with subsequent artery caliber reduction and reverse
      vascularization via the gastroduodenal artery is present. In liver
      transplantation, small-caliber hepatic arteries are higher risk factors for
      hepatic arterial thrombosis and frequent graft loss. We report a case of celiac
      trunk compression in a living-related donor and the two-step strategy we
      developed to perform a safer liver transplantation via flow-induced enlargement
      of the donor hepatic artery. A 29-year-old father was selected as a living
      related liver donor for his 4-year-old daughter. Angiography revealed celiac
      trunk compression by the median arcuate ligament with reverse vascularization of
      the middle hepatic artery via the gastroduodenal artery, a proper hepatic artery
      2 mm in diameter irrigating the left lateral segment exclusively, and a right
      hepatic artery irrigating the right lobe and segment 4. First-step division of
      the median arcuate ligament and gastroduodenal artery ligation were performed.
      Repeat angiography at the third week showed a 50% enlargement of the middle
      hepatic artery (3 mm). Second-step left lobectomy was performed at the fifth
      week. The transplantation was achieved with an arterial anastomosis between the
      middle hepatic arteries of donor and recipient. This two-step strategy including
      median arcuate ligament division provided flow-induced enlargement of the donor
      middle hepatic artery for a safer transplantation with arteries of more suitable
      calibers.

PMID- 12497227
TI  - Radiographic features of large cystic lesions of the jaws in children.
AB  - BACKGROUND: The surgical approach to cystic lesions of the jaws is either
      marsupialisation or enucleation. The treatment of choice is dependent on the size
      of the lesion, the bony integrity of the cyst and its proximity to anatomical
      structures. OBJECTIVES: To assess large (>2.0 cm) cystic lesions of the jaws
      using plain film radiography (PFR), CT, multiplanar reconstruction program (MPR)
      and three-dimensional CT (3D-CT). PATIENTS AND METHODS: Twelve children aged 7-14
      years. RESULTS: The classic radiological feature was a unilocular radiolucent
      area surrounded by a well-defined radio-opaque margin adjacent to the root of a
      non-viable tooth or associated with the crown of an unerupted tooth. Malposition
      of teeth and root resorption were more common in dentigerous cysts. The features
      seen on CT were clear and more precise than those seen on PFR. MPR, by the three
      dimensional visualisation of the jaw (axial, panoramic, and bucco-lingual),
      provided useful information for determining the outline of the cyst and its
      proximity to adjacent anatomical structures, such as teeth, nerves or maxillary
      sinus. 3-D CT further and more clearly demonstrated discontinuity in the buccal
      or palatal/lingual cortices of the jaw bone. PFR was very accurate in determining
      root resorption. CONCLUSIONS: CT with MPR and, ideally, 3-D CT should be used for
      the comprehensive diagnostic work-up and meticulous surgical management of large
      cystic lesions of the jaws in children.

PMID- 12497228
TI  - Congenital distal humeral dysplasia: a case report.
AB  - Congenital dysplasia of the humerus is very rare. It is characteristically seen
      in omodysplasia and has also been reported as one of the associated features of
      Larsen's syndrome. We report a 4-year-old girl with bilateral humero-ulnar
      dysplasia, with dislocation of the elbows, facial dysmorphism, ball-and-socket
      ankles and foot deformities. Although the elbow dysplasia is similar to that seen
      in Larsen's syndrome, other pathognomic features of Larsen's syndrome were
      absent. The changes seen in the elbows in this patient are also different from
      those encountered in omodysplasia. We believe that this condition may be a
      distinct form of skeletal dysplasia hitherto undescribed.

PMID- 12497229
TI  - Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead
      poisoning in a child with hypotonia and seizures.
AB  - We report the case of a 23-month-old male with hypotonia, developmental delay,
      and complex seizures. Radiographs revealed profound sclerosis of the metaphyses
      and epiphyses of the long and short bones in the extremities, with a unique
      pattern of distribution. Sclerosis also involved the anterior ribs, iliac crests,
      talus, and calcaneus. The skull and vertebral bodies appeared unaffected. Blood
      lead levels were normal. We believe that this constellation of clinical and
      radiographic abnormalities closely resembles osteosclerotic metaphyseal dysplasia
      (OMD) due to an autosomal recessive defect. Characteristic skeletal findings were
      instrumental in determining the diagnosis. OMD is a very rare sclerosing bone
      disorder, first described in 1993. The syndrome is characterized clinically by
      developmental delay of a progressive nature, hypotonia, elevated alkaline
      phosphatase, and late-onset spastic paraplegia. We encountered a young child with
      these neurologic symptoms who displayed sclerotic metaphyseal changes on hand
      radiographs obtained to determine the bone age. Lead poisoning, a known cause of
      metaphyseal sclerosis, was initially suspected. Careful analysis of the
      metaphyseal bone changes helped to distinguish this bone dysplasia from lead
      poisoning and other causes of metaphyseal sclerosis.

PMID- 12497230
TI  - Angiographic features of rapidly involuting congenital hemangioma (RICH).
AB  - Rapidly involuting congenital hemangioma (RICH) is a recently recognized entity
      in which the vascular tumor is fully developed at birth and undergoes rapid
      involution. Angiographic findings in two infants with congenital hemangioma are
      reported and compared with a more common postnatal infantile hemangioma and a
      congenital infantile fibrosarcoma. Congenital hemangiomas differed from infantile
      hemangiomas angiographically by inhomogeneous parenchymal staining, large and
      irregular feeding arteries in disorganized patterns, arterial aneurysms, direct
      arteriovenous shunts, and intravascular thrombi. Both infants had clinical
      evidence of a high-output cardiac failure and intralesional bleeding. This
      congenital high-flow vascular tumor is difficult to distinguish angiographically
      from arteriovenous malformation and congenital infantile fibrosarcoma.

PMID- 12497231
TI  - Congenital, solitary, large, intrahepatic arterioportal fistula in a child:
      management and review of the literature.
AB  - Congenital intrahepatic arterioportal fistula (APF) is a rare condition. In most
      cases, the symptoms and complications develop during infancy. We report here the
      incidental finding of a large and solitary congenital APF in a 13-year-old boy,
      with subsequent related clinical complications. At angiography, an APF connecting
      the left hepatic artery and the left branch of the portal vein (PV) was
      demonstrated with reversed flow in the left and main PV. The fistula was
      successfully occluded, in a single embolisation session, using an Amplatzer
      occlusion device. This was associated with immediate restoration of normal
      hepatopetal flow in the PV and followed by resolution of the clinical signs of
      portal hypertension. This patient is the oldest child with congenital
      intrahepatic APF to be reported. We emphasise the interest of using a large
      device (Amplatzer) to occlude a solitary large APF in a single session and, more
      importantly, to avoid other possible complications related to embolisation.

PMID- 12497232
TI  - Hepatic artery pseudoaneurysm following laparoscopic cholecystectomy.
AB  - The authors describe a hepatic pseudoaneurysm following laparoscopic
      cholecystectomy in a child. It arose from a hepatic artery that was ligated
      during surgery and was supplied by collaterals from the superior right branch.
      Because of the risk of hepatic infarction and recanalization of the
      pseudoaneurysm by new collaterals, the authors decided not to occlude the
      superior right branch, but to embolize the aneurysm itself with cyanoacrylate.
      Since the intra-arterial approach was not feasible, a transhepatic puncture was
      successfully performed.

PMID- 12497233
TI  - Lassoed liver: hepatic pseudo-fissure caused by ventriculoperitoneal shunt.
AB  - A 2-year-old child with a ventriculoperitoneal shunt and a shunt revision 18
      months previously developed a shunt infection. A CT scan of the abdomen was
      performed soon after the shunt catheter was removed. A peculiar invagination in
      the liver was demonstrated along the same course of a recently removed
      intraperitoneal catheter, presumably caused by the catheter. There have been no
      reported cases of deformity and pseudo-fissure of the liver, which may mimic
      pathologic processes on ultrasound or CT, caused by a ventriculoperitoneal shunt.

PMID- 12497234
TI  - Inflammatory myofibroblastic tumour of the liver in a child: CT and MR findings.
AB  - Inflammatory myofibroblastic tumour of the liver is a rare disease in children
      and is characterized by an inflammatory mass of uncertain aetiology which
      simulates a true neoplasm, often resulting in a diagnostic dilemma. We report a
      pathologically proven case of inflammatory myofibroblastic tumour of the liver in
      a 14-month-old boy with jaundice. CT and MRI showed an ill-defined, homogeneously
      enhancing mass located in the hilar portion of the liver with biliary
      obstruction. He underwent percutaneous transhepatic biliary drainage to relieve
      obstructive jaundice, followed by lobectomy and, finally, liver transplantation.

PMID- 12497235
TI  - Torsion of a giant mesenteric lipoma.
AB  - Mesenteric lipoma is a rare benign neoplastic condition that can grow to be very
      large and mimic other midgut fatty tumors. These benign tumors can cause various
      gastrointestinal symptoms such as obstruction and abdominal pain. We report the
      case of a 9-year-old boy who presented with a small bowel obstruction caused by
      torsion of a large mesenteric lipoma. This is an important but unusual tumor and
      should be considered in the differential of fatty lesions within the mesentery.

PMID- 12497236
TI  - Mesenteric lipoblastoma: case report.
AB  - We present a rare case of mesenteric lipoblastoma in a 16-month-old girl. The US,
      CT and MRI features of this unusual tumour are described and correlated with the
      pathology findings. MRI more clearly suggested the presence of fat components in
      the tumour. In addition, multiplanar MR images demonstrated the anatomical extent
      better, which was essential for successful complete tumour excision.

PMID- 12497237
TI  - Lower gastrointestinal bleeding in a newborn caused by isolated intestinal
      vascular malformation.
AB  - We report a 3-week-old neonate with an intestinal vascular malformation. The
      usual investigations performed for the examination of lower gastrointestinal
      bleeding had negative results, but ultrasound revealed bowel loops of abnormal
      calibre and altered flow in the superior mesenteric artery. Ultrasound should be
      considered a diagnostic study of primary importance when assessing a neonate with
      gastrointestinal bleeding.

PMID- 12497238
TI  - Central pontine myelinolysis secondary to cytomegalovirus hepatitis in a 10-month
      old child.
AB  - We present a 10-month-old child with central pontine myelinolysis (CPM) secondary
      to chronic active hepatitis due to cytomegalovirus (CMV) infection. A total of 35
      paediatric cases of pontine and/or extrapontine myelinolysis are reported and, to
      our knowledge, CPM secondary to CMV hepatitis in an infant has not been
      previously reported. The MRI findings are highlighted.

PMID- 12497239
TI  - Alexander's disease in a neurologically normal child: a case report.
AB  - We report the clinical and MRI findings of symmetric hyperintensity involving the
      deep and subcortical white matter of the frontal lobes in a neurologically normal
      child with macrocephaly. In this patient, a serum test for mutations in glial
      fibrillary acidic protein, used to diagnose Alexander's disease (AD), was
      positive. This case indicates an extraordinarily mild or early form of juvenile
      onset AD.

PMID- 12497240
TI  - Neuromuscular hamartoma: imaging features of a rare paediatric craniofacial
      tumour.
AB  - Neuromuscular hamartoma (also referred to as neuromuscular choristoma or benign
      triton tumour) has not previously been described in the radiological literature.
      It is a rare benign lesion composed of mature elements of striated muscle and
      neural tissue. We report a case of neuromuscular hamartoma involving the skull
      base, nasopharynx, orbit and maxilla in a 2.5-year-old child who presented with
      facial swelling. The CT and MRI appearances of this unusual soft-tissue tumour
      are emphasized, together with a discussion of the pathological findings,
      differential diagnosis and review of the literature.

PMID- 12497241
TI  - Multiple fetuses in fetu:imaging findings.
AB  - Fetus in fetu is an extremely rare developmental abnormality secondary to
      abnormal embryogenesis in a diamniotic monochorionic pregnancy. It occurs when a
      vertebrate fetus is enclosed within the abdomen of a normally developing fetus.
      This report describes the prospective diagnosis of fetus in fetu by findings on a
      plain radiograph and CT scan. At surgery, two fetus in fetu were discovered.

PMID- 12497242
TI  - Sclerosing stromal tumor of the ovary in a premenarchal female.
AB  - Sclerosing stromal tumor (SST) is a rare benign ovarian neoplasm of stromal
      origin with less than 100 cases reported in the literature. Unlike the other
      stromal tumors, thecomas and fibromas, which tend to occur in the fifth and sixth
      decades, sclerosing stromal tumors predominantly affect females in the second and
      third decades. Computed tomography (CT), magnetic resonance imaging (MRI), and
      ultrasound findings have been described, but have not been reported previously in
      the pediatric literature. We present a case of SST of the ovary in a 10-year-old
      premenarchal female, the youngest patient to our knowledge reported in the
      literature, and describe the ultrasound and CT findings with pathologic
      correlation.

PMID- 12497243
TI  - Scintigraphic detection of 'yo-yo' phenomenon in incomplete ureteric duplication.
AB  - 'Yo-yo' reflux in an incompletely duplicated renal system was demonstrated on
      (99m)Tc-mercaptoacetyltriglycine (MAG3) renal scintigraphy in a 7-year-old girl
      presenting with low-grade fever and pyelonephritis. Incomplete duplication and a
      bifid renal pelvis, which may be seen in up to 4% of the North American
      population, occasionally causes symptoms because of recurrent urinary tract
      infection or loin pain. (99m)Tc-MAG3 renal scintigraphy can demonstrate 'yo-yo'
      reflux in patients with incomplete renal duplication and should be considered in
      cases with unexplained loin pain, even if (99m)Tc-dimercaptosuccinic acid (DMSA)
      renal scintigraphy is normal.

PMID- 12497244
TI  - Unusual mesoblastic nephroma in a young child.
AB  - We report a 1-year 11-month-old girl demonstrating a large renal mass with a
      unique presentation on imaging (US, CT and plain radiography), pathology and
      histology. The imaging features did not correspond with a Wilms' tumour, the most
      commonly found renal tumour in the child of this age. The US and CT findings
      resembled a benign lesion with an unusually high fat content. Histological
      evaluation demonstrated a congenital mesoblastic nephroma, a tumour entity
      typical for the neonatal period or early infancy, with an additional unusual,
      predominantly lipomatous differentiation.

PMID- 12497245
TI  - Detection by CT scan of Penicillium sp. lesions in a patient with B-precursor
      acute lymphoblastic leukemia.

PMID- 12497246
TI  - The diagnosis of acute left-sided appendicitis with computed tomography.

PMID- 12497247
TI  - Skewed X-chromosome inactivation is associated with trisomy in women ascertained
      on the basis of recurrent spontaneous abortion or chromosomally abnormal
      pregnancies.
AB  - An increase in extremely skewed X-chromosome inactivation (XCI) (> or = 90%)
      among women who experienced recurrent spontaneous abortion (RSA) has been
      previously reported. To further delineate the etiology of this association, we
      have evaluated XCI status in 207 women who experience RSA. A significant excess
      of trisomic losses was observed among the women who had RSA with skewed XCI
      versus those without skewed XCI (P=.02). There was also a significant excess of
      boys among live births in this group (P=.04), which is contrary to expectations
      if the cause of skewed XCI was only that these women carried X-linked lethal
      mutations. To confirm the association between skewed XCI and the risk of trisomy,
      an independent group of 53 women, ascertained on the basis of a prenatal
      diagnosis of trisomy mosaicism, were investigated. Only cases for which the
      trisomy was shown to be of maternal meiotic origin were included. The results
      show a significantly higher level of extreme skewing (> or = 90%) in women whose
      pregnancies involved placental trisomy mosaicism (17%) than in either of two
      separate control populations (n=102 and 99) (P=.02 compared with total control
      subjects). An additional 11 cases were ascertained on the basis of one or more
      trisomic-pregnancy losses. When all women in the present study with a trisomic
      pregnancy (n=103) were considered together, skewed XCI was identified in 18%, as
      compared with 7% in all controls (n=201) (P=.005). This difference was more
      pronounced when a cutoff of extreme skewing of 95% was used (10% vs. 1.5% skewed;
      P=.002). Maternal age was not associated with skewing in either the patient or
      control populations and therefore cannot account for the association with
      trisomy. Previous studies have shown that a reduced ovarian reserve is associated
      with increased risk of trisomic pregnancies. We hypothesize that the association
      between skewed XCI and trisomic pregnancies is produced by a common mechanism
      that underlies both and that involves a reduction of the size of the follicular
      pool.

PMID- 12497292
TI  - [Systemic inflammatory response syndrome and primary of spontaneous intracerebral
      haemorrhage].
AB  - OBJECTIVE: Systemic inflammatory response syndrome (SIRS) without infection is a
      well known phenomenon that accompanies various acute cerebral insults. We in
      tented to determine whether SIRS was associated with outcome in patients with
      spontaneous intracerebral hemorrhage. PATIENTS AND METHODS: In patients with
      intracerebral hemorrhage, the occurrence of SIRS was assessed according to the
      guidelines of the 1992 Consensus Conference. SIRS criteria and other prognostic
      parameters were evaluated as predictors of final outcome. RESULTS: SIRS was
      highly related to poor clinical grade (Glasgow coma scale), hemorrhage volume on
      CT scan and intraventricular extension of hemorrhage. By univariate analysis,the
      occurrence of SIRS was associated with higher mortality and morbidity rates than
      was the nonoccurrence (p<0.005). CONCLUSIONS: In patients with intracerebral
      hemorrhage, SIRS reflected the extent of tissue damage and predicted a poor
      outcome.

PMID- 12497293
TI  - [Intracranial carotid artery bifurcation aneurysms].
AB  - INTRODUCTION: Intracranial carotid artery bifurcation aneurysms are infrequent
      but its clinical behavior, high risk of bleeding and complex anatomic
      relationships of the sac permit to consider these lesions as a challenge cases.
      PATIENTS AND METHODS: 497 patients harboring intracranial aneurysms were operated
      on at Manuel Ascunce Domenech Hospital, Camaguey, Cuba between January 1982 to
      august 2001. We utilized microsurgical procedures, optical magnification,
      specialized neuroanesthesia and Intensive Care Unit postoperatory following. All
      patients were evaluated clinically with World Federation Neurological Surgeon
      Scale and Glasgow Outcome Scale. RESULTS: There were 16 patients with
      intracranial carotid artery bifurcation aneurysms (3.2 %). 12 patients were under
      40 years and 50% were between 16 and 30 years old. All patients present
      intracranial bleeding. There was 87.5% of total or partial recuperation. There
      was one death only. Postoperative deficit were observed at 44% but 31%
      disappeared three month later. CONCLUSION: Intracranial carotid artery
      bifurcation aneurysms are complex anatomoclinical lesions. Clinically, we
      observed high tendency to bleed and multiplicity. Anatomically, these sacs have
      complex arterial relationship that difficult dissection and clipping. They have
      frequent postoperative morbidity. Multiple or bilateral aneurysmal sacs will be
      clipped by one surgical procedure.

PMID- 12497294
TI  - [Paraneoplastic cerebellar degeneration as initial presentation of a pancreatic
      small-cell carcinoma].
AB  - INTRODUCTION: Oat (small) cell carcinoma is the type of tumour most frequently
      associated to neurologic paraneoplastic syndromes. It is usually located in the
      lungs although it has been described in some other locations. Cerebellar symptoms
      may appear alone, associated to anti Yo antibodies ( Breast and gynaecologic
      carcinomas), or as manifestation of a more generalized paraneoplastic
      encephalopathy, associated to signs and symptoms of some other neurologic systems
      affected. CASE REPORT: A 52 year old patient consulted due to a pancerebellar
      clinical picture, which started about two months before, and later associated to
      polineuropathy. Abdominal CT showed a 4 cm mass in the head of the pancreas.
      Pathologic evaluation demonstrated a poorly differentiated small cell pancreatic
      tumour. Anti Hu antibodies in high titres were found both in serum and
      cerebrospinal fluid. DISCUSSION: The association of anti Hu immunity and
      paraneoplastic encephalomyelitis has been observed in patients with
      neuroblastoma, seminomas, colorectal, breast and prostate carcinomas and some
      types of sarcoma. Only about 1% of pancreatic malignancies correspond to small
      cell type. We have not found any previous report about the association between a
      paraneoplastic syndrome and pancreatic poorly differentiated small cell
      carcinoma.

PMID- 12497295
TI  - [Clinical neuropsychology of the surgery of temporal lobe epilepsy].
AB  - INTRODUCTION AND OBJECTIVES: The surgery of epilepsy has become a real
      alternative for the treatment of patients with drug resistant epilepsy. In this
      study we review the part played by Clinical Neuropsychology in programmes of
      surgery for epilepsy, particularly in operations designed to treat drug resistant
      temporal lobe epilepsy. DEVELOPMENT: Firstly we describe the function of the
      clinical neurologist in relation to these patients. Then we consider the main
      national and international forms of assessment. Finally we describe the main
      findings of neuropsychological investigation regarding the approach to temporal
      lobectomy. Thus we describe the main presurgical characteristics of candidates
      for surgery regarding cognition and personality. Similarly we describe what is
      known of the possibilities of finding the site of the epilepetogenic focus and
      prognosis of the results and neuropsychological consequences of the operation.
      Finally, we describe the cognitive results, particularly memory, after temporal
      lobectomy. CONCLUSIONS: Review of the literature shows how important it is for
      the clinical neuropsychologist to be involved in programmes of the surgery of
      epilepsy, studying the patients before and after surgery and assessing prognosis.
      Clinical neuropsychology is also important for predicting the post surgical
      neuropsychological results.

PMID- 12497296
TI  - [Transplantation of haematopoietic stem cells in multiple sclerosis].
AB  - INTRODUCTION AND METHOD: The idea of treating auto immune diseases which are
      resistant to conventional immunodepressive treatment by autologous
      transplantation of haematopoietic stem cells obtained from peripheral blood
      (TAPH) is based on the hypothesis that immuno ablative treatment would destroy
      the patients anti self lymphocytes and the reinfusion of stem cells would give
      rise to lymphocytes which would be tolerant of the antigens responsible for the
      auto immune response. By July 2000 90 patients with multiple sclerosis (ES) had
      received a TAPH according to data of the European Group for Blood and Marrow
      Transplantation/European League against Rheumatism (EBMT/EULAR). In the
      literature there are reports of the results obtained in 43 patients in whom EM
      was the sole indication for treatment [30 secondary progressive (SP), 10 primary
      progressive (PP) and 3 progressive relapsing (PR) ES]. The transplant related
      mortality (death within the first 100 days) was 4.6% (2/43), in both cases caused
      by infection. In the study which included 24 patients, the TAPH was considered to
      have been effective, since 92% of the patients with SP MS had no further
      progression after 3 years. However, of the patients with PP EM only 40% scored
      the same or better on the EDSS, as compared to their basal scores, at the end of
      the study. In any case, this treatment cannot be considered to cure the MS since
      the probability of patients having no signs of active disease 3 years after
      transplantation is 12% in SP MS and 0% in PP MS. CONCLUSIONS: TAPH remains an
      experimental treatment. Only in the future will it be clear whether this
      treatment is really useful for patients with multiple sclerosis.

PMID- 12497297
TI  - [Symptomatic treatment of multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis is a chronic neurological disorder which affects
      middle aged adults. It usually means serious physical, psychological, social and
      employment problems for the patients concerned. METHOD: From the anatomo
      pathological point of view, it is characterized by demyelination and axon damage
      in the central nervous system. The clinical features are variable, depending on
      the course of the disease, its clinical form and the sites of the lesions.
      Symptoms may appear in bouts, as relapses of the disorder or as a result of
      incomplete recovery from these episodes and cause severe disability. CONCLUSION:
      We review the physiopathology and most widely used treatment for management of
      the commonest symptoms of multiple sclerosis.

PMID- 12497300
TI  - [Abstracts of the 2nd LACTRIMS (Latinamerican Committee for Treatment and
      Research in Multiple Sclerosis) Congress. Monterrey, Mexico, 9-12 October 2002].

PMID- 12497301
TI  - [HTLV I associated tropical spastic paraplegia. Two case reports diagnosed in
      Paraguay].

PMID- 12497298
TI  - [Immunosuppressive medication in multiple sclerosis].
AB  - Immunosuppressive drugs have been used for decades in the treatment of multiple
      sclerosis. The recent availability of immunomodulators has caused a major change
      in the treatment of this disease, but has not meant the disappearance of the use
      of immunosuppressive drugs, some of which (such as mitoxantrone) have been
      introduced recently. At present, it is difficult to assess the precise
      indications for these drugs, since most efficacy studies were made before the
      availability of magnetic resonance imaging, on criteria which are now considered
      obsolete. Independently of their value in monotherapy, immunosuppressants may
      probably be useful in combination with immunomodulators. We review the experience
      with the most widely used immunosuppressants and mention those drugs which might
      be used in the near future.

PMID- 12497303
TI  - [The effects of axotomy on the nociceptive neurons of the leech].
AB  - INTRODUCTION: It has been described several similarities between mammalian and
      invertebrate nociceptors. Lateral N neuron, in the segmental ganglion of the
      leech Hirudo medicinalis, behave like polimodal nociceptors in mammals, meanwhile
      medial N cells is similar to mechano nociceptors (Pastor, Soria, Belmonte 1996).
      The effects of axotomy in sensory neurons in leeches are poorly understood.
      OBJECTIVE: We have focused on the electrophysiological properties of leech
      nociceptive neurons after axotomy. RESULTS: In N lateral neurons, axotomy induced
      an increase in the total membrane capacitance, membrane time constant, decrease
      in the steady state/maximum hyperpolarization rate, increment in the time
      constant of voltage relaxation of inward rectifier, increase in action potential
      duration, dV/dtmax, dV/dtmin, and maximum amplitude and duration of after
      hyperpolarization; firing threshold (always in not axotomized) and an increment
      in adaptation spike frequency. In N medial cells, axotomy produced a slight
      depolarization and a decrease in Rinput, a rise in the time constant of voltage
      relaxation of inward rectifier, a decrement of action potential maximum
      amplitude, dV/dtmax, dV/dtmin, and after hyperpolarization maximum amplitude,
      with an increase in action potential and after hyperpolarization duration.
      Finally, firing threshold increased both in axotomized and not axotomized after
      axotomy. Axotomy not only induced changes in injured cells, but modified neurons
      whose axons did not run into the cutting nerves. CONCLUSION: axotomy induces
      different changes in N lateral and N medial nociceptive cells, and it is
      suggested some kind of communication between axotomized and not axotomized cells

PMID- 12497304
TI  - [A comparison between low doses of amitriptyline and low doses of fluoxetin used
      in the control of depression in patients suffering from Parkinson's disease].
AB  - INTRODUCTION: On average 40% of all patients suffering from Parkinson s disease
      (PD) undergo bouts of depression. It is thought that this is due to a dysfunction
      in the orbitofrontal and dorsolateral circuits, together with hypometabolism in
      the orbital, caudate nucleus and frontal dorsolateral tract regions. AIMS: The
      aim of this study is to compare the effectiveness of low doses of fluoxetin with
      that of low doses of amitriptyline in controlling depression in patients with PD.
      PATIENTS AND METHODS: The study examined a total of 77 patients (34 females and
      43 males), with an average age of 68.2 years, who had been suffering from PD
      (according to the diagnostic criteria of Calne et al, in stage II of Hoehn and
      Yahr) for an average of 6.9 years. They were divided randomly into two groups
      which received fluoxetin (37 patients, dosage: 20 40 mg/day) or amitriptyline (40
      patients, dosage: between 25 and 75 mg/day). A basal evaluation and four others
      (at 3, 6, 9 and 12 months of treatment) were performed, including the STMS (Short
      test of mental status), the Hamilton scale, and extent of functional disability
      using the UPDRS. A statistical analysis was performed by comparing the variance
      of the above mentioned parameters and the c2 test with Yates correction or the
      Fisher exact two tailed test, to evaluate the reasons for dropping out. In both
      cases a value of p< 0.05 was accepted as significant. RESULTS: 58 patients
      finished the study. Drop out because of side effects only took place in the group
      that received amitriptyline (p< 0.02), which was better than fluoxetin at
      controlling the depression (p< 0.009, 0.001, 0.002 and 0.00006) at 3, 6, 9 and 12
      months, respectively. CONCLUSIONS: At an average dosage of 35.2 mg/day,
      amitriptyline is effective in controlling the depression presented by patients
      with PD. However, despite the low dosage, the side effects it caused forced 15%
      of the patients abandon the treatment.

PMID- 12497305
TI  - [Prevalence of mental retardation in teenagers with dissocial conduct disorder].
AB  - INTRODUCTION: Prevalence of adolescents with conduct disorder (CD) has been
      calculated between 4 y 10%. OBJECTIVE: To estimate the prevalence of mental
      retardation in Colombian adolescent offenders, using the Wechsler Intelligence
      Scales for Children Revised (WISC R). PATIENTS AND METHODS: 106 male adolescent
      offenders with CD, aged 12 to 16 years, and attending to institutions of re
      education in Medell n Colombia were selected in a randomized approach. WISC R
      Hispanic version was administered to the sample, using 4 verbal (information,
      vocabulary, similarities and arithmetic) and 4 performance (Picture completion,
      block design, picture arrangement, and digit symbol) subtests for calculating
      verbal, performance and full scale IQs (VIQ, PIQ, and FSIQ), according to the
      manual instructions. RESULTS: 43 participants (40.6%) obtained a FSIQ < 70, then
      they were categorized as mild mental retardation. 34 offenders (32.1%) had a FSIQ
      between 70 and 84, then they were classified as people with borderline
      intellectual functioning, only 29 participants (27.4%) obtained a FSIQ over 85.
      CONCLUSION: 72.7% of the institutionalized adolescents offenders had low
      intellectual functioning, which may be interfere with the re education programs.

PMID- 12497306
TI  - [Estimations of the prevalence of attention deficit hyperactivity disorder in
      Marabino children].
AB  - AIMS: This study reports the findings of research aimed at determining the rate
      of prevalence of attention deficit hyperactivity disorder (ADHD) in children of
      school age. SUBJECTS AND METHOD: The epidemiological study was conducted using a
      community sample extracted by means of multi stage stratified sampling according
      to socio economic level and schooling and consisted in 1,141 children of both
      sexes of school age from the city of Maracaibo. The revised Conners scales were
      used to collect data. RESULTS: The estimated prevalence of ADHD was 7.19% and we
      also obtained 0.35% for the hyperactive type, 1.14% for the disattentional
      subtype, and 5.70% for the combined type. Contrary to what was expected,
      prevalence was higher for females. It was found that 7.45% of the general sample
      scored higher on the academic problems scales, whereas for the sample identified
      as having ADHD, academic problems were 50% and the comorbidity between ADHD and
      academic problems was confirmed. CONCLUSIONS: The estimates for prevalence found
      in this study are consistent with those reported in the literature, which
      suggests that ADHD is a valid diagnosis for Marabino children.

PMID- 12497307
TI  - [Serum alpha-1 antitrypsin levels in patients with Cuban epidemic neuropathy].
AB  - INTRODUCTION: Cuban epidemic neuropathy is an emergent disease that due to its
      magnitude and health problem it was considered the most devastating outbreak of
      the XX century of the world. On the other hand it has been reported that the
      protease inhibitor, in particular alpha 1 antitrypsin has importance for the
      brain metabolic process and its genetic deficiency was produced peripheric
      neuropathy. Because of it we should decided to study the serum levels of patients
      suffering from this disease. PATIENTS AND METHODS: It has been studied serum
      alpha 1 antitripsin levels in 39 patients with peripheric Cuban epidemic
      neuropathy, six patients with the mixt variant of the disease and 10 patients
      with diabetic neuropathy. All patients has no toxic habits like alcohol and
      tobacco consumption. The quantification of alpha 1 antitrypsin was performed by
      radial immunodiffusion. RESULTS: When the median values of alpha 1 antitrypsin
      were compared no significant differences were obtained among the different
      neuropathies with a significance levels less than 0.05. There was a significant
      increased of apha 1 antitrypsin with the evolution time of the disease in the
      patients with the mixt variant and a significant correlation between alpha 1
      antitrypsin levels and age with diabetic neuropathy. CONCLUSIONS: This protease
      inhibitor looks to be involved in the physiopathology of the Cuban epidemic
      neuropathy with a decreased levels during the initial time of the disease.

PMID- 12497308
TI  - [Infiltration of the optic nerve by lymphoma. Diagnosis by magnetic resonance
      imaging].
AB  - INTRODUCTION: Systemic lymphoma with meningeal involvement is frequent and
      diagnosis is based on the clinical features, the study of the cerebrospinal fluid
      and evaluation by magnetic resonance imaging (MRI). Lymphoma with involvement of
      the orbitary region is more frequent in the optic nerve (ON) than of the eye
      itself. CLINICAL CASE: We report the case of a patient with diffuse non Hodgkin
      gastric lymphoma of the large B cell type, which coursed with amaurosis,
      exophthalmus and signs of tumorous meningeal involvement. The ophthalmologic
      study revealed a thrombosis in the central retinal vein. The MRI exploration only
      showed an infiltration of the ON with no pathological meningeal enhancement. ON
      involvement consisted in a peripheral enhancement of the sheath with obliteration
      of the subarachnoid space. This pattern accounts for the existence of an ischemic
      neuropathy by direct compression over the central retinal vein and artery. There
      are different anatomopathologic or ophthalmologic studies of neuropathy of the ON
      by lymphoma in the literature, but there is only one case of diagnosis by MRI.
      CONCLUSIONS: ON involvement can be the only radiological sign in cases of
      neoplastic tumours with meningeal involvement. The radiological pattern consists
      in a peripheral infiltration of the sheath of the ON.

PMID- 12497309
TI  - [Neurofibromatosis type 2 as a result of a de novo mutation: a case report].
AB  - INTRODUCTION: Neurofibromatosis type 2 is a dominant autosomic hereditary disease
      which courses with distinct tumours of the central nervous system and scant
      cutaneous manifestations. The increased knowledge of the natural history and the
      genetics of NF 2 acquired over the past few years has shown that clinical onset
      possibly occurs during the paediatric age and an early diagnosis of these
      patients can be decisive in the final outcome. CLINICAL CASE: A 12 year old girl
      who visited the clinic because of a month old presentation of cervical tumour,
      otalgia and dysphonia. Exploration revealed signs of cranial nerve disorder and
      the magnetic resonance (MR) showed bilateral schwannomas of the eighth cranial
      nerves. The extension study showed ocular, auditory, troncoencephalic and
      cervical spinal cord disorders. The patient died three months after hospital
      admission. The genetic study showed a de novo mutation in the NF 2 gene
      (chromosome 22q12). DISCUSSION: The identification of the various mutations that
      cause NF 2 has enabled the early diagnosis of the patient s relatives. However,
      there are still patients who have not been confirmed genetically. Furthermore, de
      novo mutations are not predictable. NF 2 diagnosis is still clinical. In the last
      few years, two disease phenotypes have been defined: mild and moderate/serious,
      which is associated with an early onset and de novo mutations. The high incidence
      rate of cataracts and other associated tumours, such as those affecting
      paraspinal and cutaneous areas together with meningiomas, which up until now
      could have gone unnoticed, has also been observed. Clinical onset in the
      paediatric age is more frequent than was expected and shows distinct and subtle
      symptoms.

PMID- 12497310
TI  - [Hemangiomas, and cutaneous and intracranial vascular deformations (Pascual
      Castroviejo syndrome tipe II ). A case report].
AB  - OBJECTIVE: To present a case with several cutaneous hemangiomas associated with
      intracranial hemangiomas and possibly with an intrahepatic hemangioma. CASE
      REPORT: A boy, 17 months old, showing several cutaneous hemangiomas and epileptic
      seizures resisting to antiepileptic medication, who also presented psychomotor
      retardation. The study by angiographic magnetic resonance (AMR ) revealed the
      presence of three small intracranial angiomas and possibly a hepatic hemangioma.
      The seizures were controlled with antiepileptic medication. CONCLUSION: This case
      shows the association of the cutaneous hemangiomas and the subjacent vascular
      alterations also hemangiomas in this patient which are included in the most
      frequent neurocutaneous disease, which is known as Pascual Castroviejo syndrome.

PMID- 12497311
TI  - [Advances in physiopathology and the treatment of neuropathic pain].
AB  - AIMS: In this paper we review the most significant studies on the treatment of
      neuropathic pain over the last few decades, as well as the most recent research
      work in which the physiopathological mechanisms of pain, with the intention of
      looking for evidence based criteria that can help us to choose the most
      appropriate treatment. METHOD: The physiopathological bases of neuropathic pain
      are founded, peripherally, on alterations in the neuronal excitability mediated
      by voltage dependent sodium channels; from the central point of view, the chief
      neurotransmitter involved is glutamate, which allows calcium to enter through the
      N-methyl D-aspartate receptor and conditions a more prolonged depolarisation and
      the activation of secondary messengers. This determines the chronification of the
      pain. Thanks to these physiopathological findings about pain, some of the new
      antiepileptics, which inhibit the sodium channels or the calcium channels,
      increase the GABA or reduce the level of glutamate in the synapses, have been
      added to the already existing classic forms of medication. CONCLUSIONS: Different
      neurophysical alterations induce the most diverse clinical manifestations, such
      as paresthesia, hyperalgesia or allodynia, regardless of the etiological
      processes that condition them. The efficiency of tricyclic antidepressants and of
      carbamazepine is made clear in different clinical studies, but the new
      antiepileptics (with the exception of gabapentin) have frequently been used in
      open clinical studies, which means there is a need for double blind controlled
      clinical trials in order to determine the efficiency and the tolerability of the
      different therapeutic alternatives in each of the clinical manifestations of
      neuropathic pain.

PMID- 12497312
TI  - [Auditory evoked potentials and alcohol: characteristics of the mismatch
      negativity component in alcoholism].
AB  - AIMS: The aim of this work is to review the effects of alcohol on the MMN
      component, to discuss its viability as a vulnerability marker for alcoholism, and
      to link it with the P300 component. METHOD: Alcohol alters the P300 and MMN
      components of auditory evoked potentials. In alcoholism, the alterations observed
      in the P300 component in risk subjects have been seen as markers of
      susceptibility to development of the illness. In the case of the MMN component,
      on the other hand, to date its viability as a vulnerability marker has only been
      evaluated in three studies, with varying results. While two of them found no
      differences, in the third and most recent it was found that risk subjects
      presented an increase in the amplitude of the MMN, which was interpreted as a
      reflection of the cortical hyperexcitability suggested by other authors and which
      was also reflected in the decrease in the P300 amplitude. CONCLUSIONS: The
      results obtained do not enable us to draw conclusions about whether the MMN
      component is altered in risk subjects for alcoholism. The differences in the
      studies that have been conducted could be due to the variations in the
      characteristics of the samples used or of the evaluation of the characteristics
      of MMN. The analysis of previous work on P300 or MMN suggests that broader, more
      homogeneous samples should be used in future research and that, in addition to
      the MMN peak, its mean amplitude in successive intervals, together with its two
      subcomponents should also be evaluated separately.

PMID- 12497313
TI  - [Primary intracerebral hemorrhage: most relevant aspects of the disease].
AB  - INTRODUCTION: Intracerebral hemorrhage is very frequently one of the most ignored
      aspects of cerebrovascular disease. AIM: To review many aspects of intracerebral
      hemorrhage ranging from its epidemiology to its etiology, pathogenesis, clinical
      manifestations, diagnosis and prognosis. METHODS: A thorough review of literature
      has been carried out paying special attention to papers published over the last
      few years. Actual tendencies in both medical and surgical treatment have been
      analyzed and some ideas for treatment have been derived from this review.
      CONCLUSIONS: It is obvious that there are important lacunes that affect many
      aspects of intracerebral hemorrhage management. Therefore we should assist in the
      near future to the performance of different trials that would come to offer data
      which reduce the uncertainties that affect this pathology.

PMID- 12497314
TI  - [Clinical features of relapsing remitting-multiple sclerosis. Prognostic
      factors].
AB  - Multiple sclerosis is the most frequent chronic neurological disease in young
      adults of the white population in developed countries. The diagnosis has been
      notably improved by the use of universal diagnostic criteria and by the
      extraordinary help of the paraclinical methods of laboratory studies, evocated
      potentials and particularly magnetic resonance imaging. Nowadays there are
      consensus criteria for the classification of the different clinical subtypes.
      Relapsing remitting multiple sclerosis is the most frequent subtype and
      eventually evolves to a secondary progressive form. Ultimately there have been
      notably advances in the knowledge of the natural history and of the pathogenetic
      mechanisms of the disease, which has permitted a more precocious therapeutic
      intervention, that ideally will provide a more benign prognosis for this disease.

PMID- 12497315
TI  - [Primary progressive multiple sclerosis].
AB  - Mainly progressive multiple sclerosis (MPMS) is an uncommon clinical form of
      multiple sclerosis which includes 10 20% of all patients with the disorder. MPMS
      shows certain clinical characteristics which differentiate it from other forms of
      progression of the disease. We review the immunological and radiological
      behaviour of this clinical form, and discuss recent classifications of the
      disease and new diagnostic criteria. Finally we comment on the few therapeutic
      options currently available for these patients and their future prospects.

PMID- 12497316
TI  - [Impairment, disability and handicap scales in multiple sclerosis].
AB  - INTRODUCTION AND METHOD: In recent years the need to create scales for measuring
      the dysfunction or impairment suffered by patients with multiple sclerosis has
      increased. The aim of the scales that measure neurological impairment is two
      fold: to homogenise the data from different series so that studies into the
      prognosis and natural history of the disease can be compared, and to measure the
      changes in the progress of the disease when a therapy has been established. Over
      the past few years a large number of scales have appeared that attempt to redress
      the shortcomings of the EDSS (Expanded Disability Status Scale). The latest of
      these, the MSF Composite, manages to overcome the statistical problems of the
      EDSS and enables significant differences between two groups to be detected when
      studying the effect of a treatment. CONCLUSIONS: In the coming years we will
      possibly witness a joint use of several of the scales described, and both the
      EDSS and the Composite will be employed together in the evaluation of patients in
      therapeutic protocols, perhaps together with a quality of life scale.

PMID- 12497317
TI  - [Preventive treatment of multiple sclerosis. Rules for treatment with
      immunomodulators].
AB  - INTRODUCTION AND METHOD: At present treatment of multiple sclerosis (EM) is a
      challenge for neurologists in general and specialists in EM in particular, who
      have the problem of digesting the avalanche of information they receive. Use of
      immuno modulators has shown that it is possible to change the natural course of
      the disease and improve life expectancy in EM. Both the number of exacerbations
      of EM and the overall improvement benefit from such treatment. Immunomodulators
      have an established place in the treatment of the remitting relapsing form,
      although its efficacy seems to become less when it is used at more advanced
      stages of EM and seems to have been ruled out for progressive primary forms.
      Immunomodulators may be useful during initial stages of the disorder in the first
      episodes before a definite diagnosis has been established, although it is obvious
      that markers for prognosis are still needed. MR and cerebrospinal fluid studies
      may be useful for this. CONCLUSION: Patient selection is essential to obtain good
      results. Although it is not fully established, it seems that early use of high
      doses improves long term control of the disease.

PMID- 12497542
TI  - Serious infections caused by enteric gram-negative bacilli--mechanisms of
      antibiotic resistance and implications for therapy of gram-negative sepsis in the
      transplanted patient.
AB  - The Enterobacteriaceae (eg, Escherichia coli, Klebsiella spp., Enterobacter spp.)
      are common causes of intraabdominal, respiratory tract, and bloodstream
      infections in transplant recipients. Antibiotic resistance in these organisms is
      increasing. The major mechanism of resistance to cephalosporins is beta-lactamase
      production. The most important beta-lactamases are the inducible group 1
      cephalosporinases, which are resistant to beta-lactamase inhibitors, and the
      plasmid-mediated extended-spectrum beta-lactamases (ESBLs). Organisms producing
      these beta-lactamases also may be resistant to quinolones and aminoglycosides by
      different mechanisms. A worrying recent development has been the detection of
      plasmid-mediated carbapenemases, which can inactivate antibiotics such as
      imipenem and meropenem. In general, third-generation cephalosporins should be
      avoided in the therapy of serious infections in transplant recipients because of
      the common occurrence of cephalospo-rinases in the Enterobacteriaceae. Antibiotic
      options are becoming more limited as the prevalence of resistance mechanisms in
      gram-negative bacilli increases.

PMID- 12497543
TI  - Antiviral resistance in cytomegalovirus: an emerging problem in organ transplant
      recipients.
AB  - In the era of more aggressive immunosuppressive regimens and antiviral
      prophylaxis, ganciclovir-resistant cytomegalovirus (CMV) has been recognized as
      an important clinical problem in organ transplant recipients. Among the various
      solid-organ transplant (SOT) recipients, lung transplant recipients appear to be
      disproportionately affected. Ganciclovir-resistant CMV appears to be a relatively
      late posttransplant complication and is seen predominantly among CMV-seronegative
      recipients of organs from seropositive donors, particularly in the setting of
      potent immunosuppression and prolonged exposure to ganciclovir (especially oral
      ganciclovir). Limitations in current diagnostic methods mandate a high clinical
      index of suspicion. In high-risk patients in whom ganciclovir resistance is
      clinically suspected, while awaiting laboratory confirmation of resistance,
      empiric addition of intravenous foscarnet, often combined with reduction in
      immunosuppression and CMV hyperimmune globulin, are commonly used. 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- 12497544
TI  - Mycobacterial infections in organ transplant recipients.
AB  - Tuberculosis has a major adverse impact on solid organ transplant recipients;
      this article attempts to define this fact. The prevalence of posttransplant
      tuberculosis is increasing globally and currently is 13.7% at our center. The
      transplant surgery divides the continuum of pretransplant tuberculosis and
      posttransplant tuberculosis; immunosuppression accounts for a greater severity of
      the latter. Cyclosporin and tacrolimus are associated with an earlier onset of
      tuberculosis when compared with prednisolone and azathioprine immunosuppression.
      Disseminated disease is more common in nonrenal transplants. The risk for
      developing posttransplant tuberculosis in renal transplant recipients increased
      2.25 times independently with cytomegalovirus (CMV) and twice with chronic liver
      disease; OKT3 treatment enhances the risk 1.8-fold. Tuberculosis occurring after
      2 years of transplantation, diabetes mellitus, posttransplant diabetes mellitus,
      chronic liver disease, CMV, and deep mycoses each independently confer a risk,
      1.5-times or higher, for death. Disseminated disease entails a 2-fold risk.
      Treatment with or without rifampicin is possible; the former is associated with a
      higher risk for allograft rejection. Isoniazid prophylaxis is recommended for
      high-risk patients with apparent clinical efficacy. However, in endemic areas,
      attendant liver disease makes it a difficult goal.

PMID- 12497545
TI  - Burkholderia cepacia infection and lung transplantation.
AB  - Burkholderia cepacia has emerged as an important pathogen in patients with cystic
      fibrosis (CF) undergoing lung transplantation. Taxonomic analyses have divided B.
      cepacia into 7 closely related species called genomovars. The prevalence of B.
      cepacia infection ranges from 2% to 13% in CF patients with genomovar III being
      most prevalent. Risk factors for the acquisition of B. cepacia include greater
      severity of underlying CF, increasing age, having a sibling colonized with B.
      cepacia, and previous hospitalizations. One-year survival in patients with CF
      undergoing lung transplantation usually have been reported to be less than 70%.
      The antimicrobial resistance pattern of B. cepacia has correlated with
      inconsistent effect on survival. Presence of genomovar III also has been linked
      with survival of B. cepacia-infected patients; the survival rates were inferior
      for genomovar III as compared with non-genomovar III patients. Standard infection
      control techniques including isolation of both colonized and noncolonized
      individuals with frequent sputum culture have been recommended to prevent CF
      patients from acquiring B. cepacia infection. B. cepacia is inherently resistant
      to antipseudomonal antibiotics, colistin, and polymyxin. The combination of 2 or
      more antibiotics usually is recommended for the treatment of B. cepacia
      infections. Studies delineating the epidemiology and influence of B. cepacia
      infection on lung transplantation are warranted. This is a US government work.
      There are no restrictions on its use.

PMID- 12497546
TI  - Infectious pulmonary complications in lung transplant recipients.
AB  - Pulmonary infections are the most common cause of morbidity in the lung
      transplant population. Prompt recognition and treatment is necessary to prevent
      poor outcomes. An understanding of the temporal relationship between
      immunosuppression and the risk for developing infection can assist the clinician
      with appropriate treatment. Bacterial pneumonia is common within the first 4
      months after transplantation whereas cytomegalovirus (CMV) infection or disease
      becomes prevalent after the discontinuation of prophylaxis in at-risk patients.
      Fungal infections, especially aspergillosis, can be fatal if not treated early
      and the risk for infection is present throughout the transplant period. Community
      acquired viral infections present with upper-respiratory symptoms and wheezing
      that may lead to a chronic decline in lung function. Suspicion of a pulmonary
      infection in these immunosuppressed individuals should lead to an urgent
      diagnostic bronchoscopy and empiric antimicrobial therapy.

PMID- 12497547
TI  - Phaeohyphomycotic infections in solid organ transplant patients.
AB  - Phaeohyphomycoses are darkly pigmented fungi that rarely cause infection in
      immunocompetent persons. In the past 2 decades these fungi increasingly have been
      reported as pathogens that cause significant morbidity and mortality in the
      immunocompromised host, especially solid organ transplant recipients. Clinical
      manifestations range from superficial lesions to disseminated infections.
      Exophiala spp. and Alternaria spp. account for the great majority of these
      infections. Treatment should include complete surgical excision of the lesions
      that are accessible combined with antifungal therapy, especially when invasive or
      systemic infection is present. Itraconazole usually suffices if only subcutaneous
      lesions are present; however, if the infection is systemic or it involves the
      central nervous system, the addition of amphotericin B is required. New
      investigational azoles also should be considered in these types of infections.
      This is a very heterogenous group of fungi and as such the sensitivities to
      antifungal agents is variable. Therefore, sensitivities should be obtained on
      every fungal isolate.

PMID- 12497548
TI  - Bronchiolitis obliterans and lung transplantation: evidence for an infectious
      etiology.
AB  - Bronchiolitis obliterans (OB) or bronchiolitis obliterans syndrome (BOS) remains
      a major hurdle in the long-term survival of lung transplant recipients. The
      pathogenesis of OB or BOS remains to be fully discerned, but it is hypothesized
      that allogenic or nonallogenic insults result in the release of chemokines and T
      lymphocytes propagating the injury and ultimately recruiting fibroblasts
      culminating in intraluminal proliferation. Infectious agents, with or without
      other exogenous factors, have been proposed to have a contributory role in the
      development of OB or BOS. Cytomegalovirus (CMV) is an immunomodulating virus that
      may lead to persistent stimulation of T cells with the release of chemokines that
      may promote OB. Animal studies have correlated the development of OB with CMV
      infection. However, assessment of CMV as a risk factor for the development of OB
      or BOS in clinical studies has yielded conflicting results. CMV infection was
      noted to have a hazard ratio of 1.62 in one study, whereas CMV pneumonitis was
      associated with relative risk of 2.3. Additional studies did not find a higher
      risk for developing OB or BOS with CMV. Other viruses including respiratory
      syncytial virus and parainfluenza viruses can promote epithelial damage and act
      synergistically with chronic rejection in the development of OB. A higher (47%)
      incidence of BOS has been noted during the respiratory virus season. The evidence
      of Pneumocystis carinii pneumonia or other infectious episodes causing OB is
      lacking. Thus, although the role of infectious agents in the development of OB or
      BOS is biologically plausible, an incontrovertible association between infection
      and OB or BOS has not been documented. This is a US government work. There are no
      restrictions on its use.

PMID- 12497549
TI  - HIV, Pneumocystis carinii pneumonia, and pneumothoraces.

PMID- 12497550
TI  - Caregivers of people with Alzheimer's disease: a qualitative study from the
      Indian 10/66 Dementia Research Network.
AB  - BACKGROUND: Dementia is a rapidly growing problem in all parts of the developing
      world. Such societies are characterised by low levels of awareness regarding
      dementia as a chronic degenerative brain syndrome, and by an absence of
      supportive health and welfare services. There is reliance upon families as the
      cornerstone of support and care. However, surprisingly little is known of the
      care arrangements for people with dementia and the strain experienced by their
      family caregivers. METHOD: In a qualitative study of 17 caregivers of people with
      Alzheimer's disease identified through an innovative case-finding program in
      Thrissur, South India, we obtained information on the range of care arrangements,
      attitudes towards care giving roles and sources of strain. RESULTS: The majority
      of caregivers were young women, often daughters-in-law of women with dementia.
      The principal sources of caregiver strain were behavioural problems associated
      with the dementia syndrome, and incontinence. Strain was exacerbated by the lack
      of supportive response by local health services, and by lack of support and,
      sometimes, criticism from other family members. Family conflict was commonly
      encountered. The majority of caregivers experienced significant deterioration in
      their mental health. One caregiver unfortunately committed suicide after the
      death of her husband. CONCLUSIONS: There is a clear need for more education,
      advice and support for families affected by dementia. Community services in
      developing countries should consider training existing domiciliary outreach
      services, the community-based multi-purpose health workers, to identify and
      support family caregivers.

PMID- 12497551
TI  - Neuropathological evidence for ischemia in the white matter of the dorsolateral
      prefrontal cortex in late-life depression.
AB  - BACKGROUND: Signal hyperintensities on magnetic resonance imaging in late-life
      depression are associated with treatment resistance and poor outcome. These
      lesions are probably vascular in origin and proposed sites for vascular damage
      include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex
      (ACC). METHODS: We therefore examined white matter in these areas for
      microvascular disease and evidence of ischemia using intercellular adhesion
      molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained
      postmortem tissue from elderly depressed (n = 20) and control (n = 20) subjects
      and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using
      quantitative image analysis in sections of the DLPFC, ACC and occipital cortex
      (OC; control area). RESULTS: We found a significant increase in ICAM-1 in the
      deep white matter of the DLPFC in the depressed group (p = 0.01) and a trend
      towards an increase for VCAM-1 (p = 0.10). In the gyral white matter there was a
      trend towards significance for both molecules (p = 0.07 and 0.10). No differences
      were found in the ACC or OC or for microvascular disease in any area.
      CONCLUSIONS: These findings are consistent with white matter ischemia in the
      DLPFC and lend support to the 'vascular depression' hypothesis. They implicate
      the DLPFC as an important site in the pathogenesis of late-life depression and
      have major implications for the understanding and management of late-life
      depression and raise the possibility of novel treatments being introduced in the
      future.

PMID- 12497552
TI  - The role of depressive symptoms in recovery from injuries to the extremities in
      older persons. A prospective study.
AB  - BACKGROUND: Previous research suggested that depressive symptoms play a role in
      recovery after hip fracture. However none of these studies were prospective and
      included only patients with hip fractures. OBJECTIVE: To examine the effect of
      depressive symptoms on the recovery of (instrumental) activities of daily living
      after fall-related injuries to the extremities in older persons. DESIGN:
      Prospective cohort study. METHODS: Data were collected from 168 older persons at
      baseline, prior to their injuries (hip fractures, other fractures or contortions
      and dislocations), and 8 weeks, 5 months and 12 months after their accident.
      Hierarchical multiple regression analysis was used to study the impact of
      depressive symptoms (as assessed with the Hospital Anxiety and Depression Scale;
      HADS) on disability (as assessed with the Groningen Activity Restriction Scale;
      GARS) after the injury while adjusting for several covariates. RESULTS:
      Depressive symptoms at baseline were not predictive for disability after the
      injury when covariates were taken into account. However, depressive symptoms 8
      weeks after the fall were significantly related to disability at 8 weeks, 5
      months and even 12 months after the injury. In addition, disability levels before
      the injury were highly predictive for recovery later on. Severity of injury was
      particularly predictive for disability at 8 weeks while age (which may generally
      represent the amount of physiological reserve) predicted disability at 5 and 12
      months after the injury. Cognitive functioning 8 weeks post-injury was, in
      contrast to previous research, not predictive for recovery when covariates were
      taken into account. CONCLUSIONS: Pre-injury levels of disability and post-injury
      depressive symptoms are associated with recovery and may warrant concern and
      special attention in clinical practice.

PMID- 12497553
TI  - Psychopathology and autobiographical memory in stroke and non-stroke hospitalized
      patients.
AB  - BACKGROUND: Psychopathology and autobiographical memory were investigated in a
      cohort of stroke and non-stroke hospitalized patients. Both these cohorts have
      been identified as having high levels of psychopathology (Katon and Sullivan
      1990; Burvill et al., 1995). Difficulties recalling specific autobiographical
      memories (overgeneral memory) have been identified as important psychological
      variables in depression and predictors of outcome (Williams and Scott 1988;
      Brittlebank et al., 1993). Intrusive autobiographical memories have also been
      found to be associated with depression and overgeneral memory in depressed women
      (Kuyken and Brewin, 1995) and depressed cancer patients (Brewin et al., 1998a).
      This study looked at levels of psychopathology and autobiographical memories in
      stroke and non-stroke hospital patients. METHOD: 417 patients were screened, of
      the 176 eligible 103 agreed to participate (54 stroke and 49 non-stroke).
      Participants were assessed for overgenerality using the Autobiographical Memory
      Test and intrusiveness of memories using the Impact of Events Scale. Also
      assessed were PTSD-like symptoms (PCL-S), mood (HADS, GHQ-28) and cognitive
      ability (MMSE, verbal fluency, digit span and estimated pre-morbid IQ). RESULTS:
      No significant differences were found between stroke and non-stroke patients on
      severity of depression, anxiety, severity of PTSD-like symptoms or
      autobiographical memories. Backward multivariate regression analyses for combined
      data (stroke and non-stroke) indicated that overgeneral memory recall, intrusive
      memories of past events and intrusive memories of illness were significant
      independent predictors of depression (HADS). Avoidance of intrusive memories and
      reported childhood distress were not predictors of overgeneral memory recall.
      Significant predictors of overgeneral memory recall were; Gender, antidepressant
      medication, and estimated IQ. CONCLUSION: Significant levels of psychopathology
      were identified in this cohort. However, there were no significant differences in
      the levels of depression, anxiety, PTSD symptoms and autobiographical memory
      between stroke and non-stroke hospitalized patients. Of particular interest was
      the finding that PTSD-like symptoms did not appear to be influenced by the nature
      of the person's illness. In combined data (stroke and non-stroke)
      autobiographical memories (intrusive images of their illness, intrusive memories
      of other events and overgeneral memory recall variables) were significant
      predictors of depression in this cohort. This suggests that psychological
      intervention of memory processes may be a worthwhile target in psychological
      intervention for depression in these cohorts. Gender, cognitive impairment,
      antidepressant medication, and estimated IQ were significant predictors of
      overgeneral memory recall and further investigation into the validity of these
      findings are warranted. Suggestions for further research and limitations of the
      study are also discussed.

PMID- 12497554
TI  - Differences in community mental health literacy in older and younger Australians.
AB  - BACKGROUND: Depression has been traditionally considered to increase with age,
      although that may be due to sampling of those who have presented with depressive
      conditions. It is now recognised that patients' understanding of depression and
      beliefs about its appropriate treatment, mental health literacy, influences
      treatment-seeking behaviour. OBJECTIVES: This study delineates depression, recent
      use of health services and mental health literacy in a random and representative
      community sample of younger and older South Australians. METHODS: Depression,
      health service utilisation and mental health literacy were assessed in a random
      and representative sample of 2010 South Australians. Results for those aged
      between 65 and 74 years (n=300) and those aged 15 to 24 years (n=521) were
      compared. RESULTS: Compared with the younger group, older subjects did not report
      greater levels of current depression although they were more likely to have seen
      a medical practitioner in the last 12 months and be taking antidepressants.
      However, their mental health literacy in terms of recognition of a mental health
      problem in a vignette was somewhat poorer and fewer recommended treatment from a
      counsellor, telephone service or psychologist and more considered that a
      psychiatrist would be harmful. They also more often perceived the clergy as
      helpful. CONCLUSIONS: Depression was not more common among older than younger
      members of the community. Despite recognising depression in a vignette less often
      and perceiving less likelihood of help from several different mental health
      professionals, those in the older group were more likely to receive
      antidepressant medication and to have recently consulted a medical practitioner.

PMID- 12497555
TI  - Ethics and dementia: mapping the literature by bibliometric analysis.
AB  - OBJECTIVES: This paper reports on a bibliometric analysis of keywords in the
      literature on ethics and dementia during the period 1980-2000. METHODS: Keywords
      were drawn from titles, abstracts and keyword fields of 14 bibliographic
      databases and clustered in to 19 categories. These categories were then examined
      for their frequency and co-occurrences. The strength of relationships between
      these categories is mapped using the metaphor of the 'night sky' showing
      constellations of issues and changes over time. RESULTS: Four categories appear
      consistently and frequently in the literature: professional care, end-of-life
      issues, decision-making and treatment. Other issues come and go (such as quality
      of-life issues) while others appear to respond to outside events (e.g. feeding
      issues). The research literature is based predominantly on surveys or studies
      soliciting responses to predefined issues. Little research has been undertaken to
      establish the range of ethical issues for either family members or professionals.
      DISCUSSION: We discuss the domination of the literature by four categories of
      ethical issues, the new and emerging areas of ethical interest and those areas
      that are triggered by external events such as legal cases. We also discuss some
      of the limitations of the study and note some omissions in the literature.
      CONCLUSION: During the period 1980-2000 the research literature has been
      dominated by surveys and studies soliciting views on predefined issues with
      relatively few in-depth, open-ended qualitative studies.

PMID- 12497556
TI  - Adult day service use and reductions in caregiving hours: effects on stress and
      psychological well-being for dementia caregivers.
AB  - BACKGROUND: The objective of this study was to determine whether adult day
      service use interacts with decreases in primary caregiving hours (i.e. the time
      caregivers spent on activities of daily living/instrumental activities of daily
      living, memory problems, and behavior problems for patients) to alleviate
      caregiver stress and negative mental health over time. METHODS: Three-month
      longitudinal data from the Adult Day Care Collaborative Study (n=400) were used.
      RESULTS: Decreases in memory problem hours among adult day service users were
      associated with reduced feelings of role overload; decreases in ADL hours among
      non-users were associated with decreases in worry and strain over a three-month
      period. CONCLUSION: The findings suggest that adult day services are potentially
      effective in restructuring caregiving time and providing respite to family
      members.

PMID- 12497557
TI  - Accuracy of the 15-item geriatric depression scale (GDS-15) in a community sample
      of the oldest old.
AB  - BACKGROUND: Cognitive impairment is common in the oldest old. This might
      influence the sensitivity and specificity of the 15-item Geriatric Depression
      Scale (GDS-15). Few studies, however, have included subjects older than 85 years
      to evaluate the GDS-15 as a screening instrument for depression. OBJECTIVE: To
      assess the sensitivity and specificity of the GDS-15 in a community sample of the
      oldest old. METHODS: Seventy-nine subjects aged 85 and over were enrolled in the
      study. The GDS-15 and the Mini-Mental State Examination (MMSE) were administered
      by a trained interviewer. Within two days the Geriatric Mental State
      (GMS)/AGECAT, was administered to obtain a clinical diagnosis of depression.
      RESULTS: Eight subjects (10%) were diagnosed with clinical depression. At a cut
      off point of 3/4 the sensitivity and specificity of the GDS-15 were 88% and 76%
      respectively. In the group with MMSE scores of 28 and higher sensitivity was
      unaffected at all cut-off points while specificity increased. In the group with
      MMSE scores below 28 sensitivity was also unaffected at all cut-off points while
      specificity decreased. CONCLUSION: The GDS-15 is a suitable instrument to
      diagnose depression in the general population of the oldest old. The optimal cut
      off point depends on its intended use. In subjects with cognitive impairment the
      accuracy should be investigated further.

PMID- 12497558
TI  - Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration.
AB  - BACKGROUND: Frontotemporal lobar degeneration (FTLD) is commonly associated with
      behavioural disturbances such as disinhibition and aggression; these often result
      in the use of neuroleptic medication. METHODS: All available case notes of
      patients attending a specialist cognitive disorders clinic with a diagnosis of
      FTLD were selected. This gave 100 subjects (62 male, 38 female). RESULTS: In 61
      patients significant behavioural disturbances were present. Of these patients, 24
      had been prescribed neuroleptics. Significant extrapyramidal side effects were
      reported in eight patients (33%); in five patients these were severe enough to
      cause severe mobility problems and in one patient resulted in impaired
      consciousness. In some instances the extrapyramidal side effects took weeks to
      wear off. CONCLUSION: These results suggest that patients with FTLD may, as in
      Lewy body dementia, be particularly sensitive to the extrapyramidal side effects
      of neuroleptics. We suggest that neuroleptics should be used cautiously in FTLD
      and treatment should be started at low doses avoiding depot preparations until
      further prospective studies have been performed.

PMID- 12497560
TI  - A comparative study of stress and burnout among staff caregivers in nursing homes
      and acute geriatric wards.
AB  - OBJECTIVE: To compare levels of stress and burnout among staff caregivers in
      nursing homes and acute geriatric wards of general hospitals. METHODS: A cross
      sectional survey was conducted in three nursing homes (total of 522 beds, 270
      caregivers) and nine geriatric sections of general hospitals (total of 371 beds,
      280 caregivers). Staff caregivers were asked to answer a four-part questionnaire
      made up of socio-demographic data, the General Health Questionnaire (GHQ-12), the
      Maslach Burnout Inventory (MBI) and the Stressful Events Questionnaire (SEQ).
      RESULTS: 355 carers (172 from nursing homes, 183 from acute geriatric wards)
      answered the questionnaire (response rate 66%). Bivariate analysis reveals that
      general hospital carers show higher GHQ scores, higher MBI-Depersonalisation (DP)
      and Emotional Exhaustion (EE) sub-scores and lower MBI-Personal Accomplishment
      sub-scores. Stressful Events (as revealed by the SEQ) are more frequently
      reported by general hospital carers, particularly events related to patients'
      behavioural disorders. Multivariate analysis shows that general hospital work
      setting, professional role, female gender and patient/carer ratio are significant
      explanatory variables of a high MBI-EE sub-score, while general work setting and
      disability are the best explanatory variables of a high MBI-DP sub-score.
      Professional role and general hospital work-setting are independent factors in a
      low MBI-Personal Accomplishment (PA) sub-score. CONCLUSION: These results appear
      to show that levels of stress and burnout among staff caregivers are moderate in
      acute geriatric wards, but significantly higher than in nursing homes. This
      suggests that increasing the rate of trained staff and improving staff support
      for instance by the implementation of Consultation-Liaison (C-L) Psychiatry
      and/or continuing education programmes-could be needed mostly in acute geriatric
      wards.

PMID- 12497559
TI  - A three-factor analytic model of the MADRS in geriatric depression.
AB  - OBJECTIVE: Major depression is a heterogeneous disorder, perhaps comprising
      several clinical subtypes or subgroups of symptoms. This study examined whether
      items on the Montgomery-Asberg Depression Rating Scale (MADRS) form distinct
      symptom subgroups among geriatric depressive patients that might form the basis
      of new outcome measures for tracking treatment effects. METHOD: The study
      examined a sample of 225 adults age 59 and older diagnosed with major depression.
      Factor analysis with oblique rotation was used to analyze baseline MADRS item
      scores. RESULTS: Three distinct interpretable factors were obtained; all ten
      items loaded <0.60 on a domain. The first factor, dysphoric apathy/retardation,
      comprised five items: apparent sadness, reported sadness, lassitude, reduced
      concentration, and inability to feel. Psychic anxiety, the second factor,
      included three items: inner tension, pessimistic thoughts, and suicidal thoughts.
      The third factor, vegetative symptoms, resulted from items involving sleep and
      appetite. CONCLUSIONS: The study produced three interpretable MADRS factors
      reflecting geriatric depression dimensions that may be useable to monitor focused
      treatment outcomes.

PMID- 12497561
TI  - Assessing the efficacy of cholinesterase inhibitor drugs.

PMID- 12497562
TI  - Outcomes of Alzheimer's disease treatment: the Italian CRONOS project.

PMID- 12497563
TI  - Dementia in footballers.

PMID- 12497564
TI  - Stop all the clocks (W H Auden).

PMID- 12497566
TI  - Design of a new suture practice card for microsurgical training.
AB  - Suturing technique is of paramount importance in microsurgery. Basic training in
      this technique can be done using the practice card, a purpose-made polyurethane
      card. A practice card has been designed in the Minimally Invasive Surgery Centre
      to closely resemble microsurgical requirements in order to practice and learn
      correct microsuturing maneuvers. This practice card is a key part of
      microsurgical training. After many years of experience, and based on a survey we
      conducted, we can conclude that this practice card is essential for step-by-step
      microsurgical training. Using this card, the number of animals required to attain
      necessary microsurgical skills is reduced significantly. Furthermore, costs are
      also reduced, and the trainee can avoid mistakes during training with live
      animals, thus optimizing results.

PMID- 12497567
TI  - Effect of nondepleting anti-CD4 monoclonal antibody (Rib 5/2) plus donor antigen
      pretreatment in peripheral nerve allotransplantation.
AB  - Peripheral nerve allotransplantation allows the reconstruction of injuries with
      long nerve gaps that are otherwise unsalvageable. In this study, the efficacy of
      anti-CD4 monoclonal antibody (mAb) combined with donor antigen pretreatment in
      prolonging the survival of short peripheral nerve allografts was investigated in
      a rodent model. Such an approach could potentially avoid the need for systemic
      immunosuppression and its concomitant morbidities. Buffalo rats received either
      nerve isografts or nerve allografts from Lewis rats. Untreated isograft and
      allograft groups were used as controls. Allograft recipients received either a
      single dose of RIB 5/2, a nondepleting anti-CD4 mAb, a single dose of Lewis
      splenocytes, or both antigen and RIB 5/2, 7 days prior to transplantation. Flow
      cytometric analysis verified that the T-lymphocyte population was maintained,
      while CD4 expression was downregulated by RIB 5/2. Histologic evaluation
      demonstrated better regeneration in the allograft recipients receiving both donor
      antigen and antibody, compared to recipients of untreated allografts or treatment
      with antigen or antibody alone.

PMID- 12497568
TI  - Vein grafting with telescoping anastomoses for repair of a double-cut artery.
AB  - The rat femoral artery was cut in two places, and the telescoping anastomosis
      technique was used for all vascular repairs in combination with vein grafting, to
      determine whether the telescoping technique could safely be used more than three
      times for repair of an artery that has been injured at two places. One cut was
      repaired with vein grafting, and the other with either a telescoping anastomosis
      (the triple group) or with a second vein grafting (the quadruple group). The
      patency rate 3 weeks postoperatively was 86.4% for the triple group, and 90.5%
      for the quadruple group. Although tension of the repaired vessel was kept low by
      vein grafting, and deformities of the inserted vessel were carefully minimized,
      the patency rate was not 100%. It appears that a telescoping anastomosis should
      not be used more than three times on the same artery in combination with vein
      grafting.

PMID- 12497569
TI  - Traction injury of common peroneal nerve associated with multiple ligamentous
      rupture of the knee: a case report.
AB  - We report on a case of a 19-year-old male student who sustained a hyperextension
      injury to his left knee while playing rugby, which resulted in a traction injury
      of the common peroneal nerve and multiple ligamentous injuries at the knee joint.
      The damaged part of the common peroneal nerve was resected, and an end-to-end
      suture was performed, because the gap between the nerve ends was small enough to
      allow closure with little mobilization. Now, 2.5 years after the surgery, the
      patient shows remarkable recovery. This result suggests that end-to-end suture is
      an ideal procedure for nerve traction injury, if the nerve ends can be closed
      without tension, without excessive flexion of the adjacent joint.

PMID- 12497570
TI  - Protective effects of ligustrazine on ischemia-reperfusion injury in rat kidneys.
AB  - To investigate the protective effects of ligustrazine on renal ischemia
      reperfusion injury, the influence of ligustrazine injection on plasma superoxide
      dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1), as well as
      changes of morphology of renal tubules, were studied in rat kidney models with
      ischemia-reperfusion injury. The results showed that in the group treated with
      ligustrazine, the plasma SOD level was significantly higher than that of the
      control group (P < 0.05), but levels of plasma MDA and ET-1 and the pathological
      grading of injured renal tubules were significantly lower than those in the
      control group (P < 0.05). These findings suggest that ligustrazine has protective
      effects against ischemia-reperfusion injury in rat kidneys.

PMID- 12497571
TI  - Microscopic vs. endoscopic assisted harvesting and transplantation of free groin
      flaps: a comparative experimental study in the rat model.
AB  - Advances in video technology can now permit the surgeon to view a microsurgical
      field on a video monitor without the necessity of physically looking through the
      microscope eyepieces. In this project, we investigated the possibility of the
      performance of rat groin free-flap harvesting and transplantation with the visual
      assistance of the endoscope, and compared it with the conventional operating
      microscope, not for its replacement but as an alternative operating tool that may
      be preferred by a younger generation of microsurgeons or in certain operative and
      financial situations. Although there were not many technical differences between
      the microscope and the endoscope, we recorded significantly shorter operative,
      harvesting, and transplantation times by using the endoscope. The endoscope seems
      to be a promising new tool in performing microsurgery, with better handling and
      greater physical comfort for the surgeon. It is reliable, time-efficient, and
      cost-effective.

PMID- 12497572
TI  - Effect of allopurinol, superoxide-dismutase, and hyperbaric oxygen on flap
      survival.
AB  - The effect of allopurinol, superoxide-dismutase, and hyperbaric oxygen was
      compared on axial pattern skin flap survival. An abdominal flap based on the
      inferior epigastric pedicle was raised in rats for this purpose. Three
      experimental groups were studied. In the first group, adult male Wistar rats
      received 50 mg/kg I.P. of allopurinol. The second received 20,000 I.U./kg of
      superoxide-dismutase. The third group was submitted to hyperbaric oxygen therapy.
      The flaps were exposed to 8-h warm ischemia. Flap survival was evaluated on
      postoperative day 7. All flaps survived, and the mean survival areas were 63.53%,
      83.03%, and 55.98%, respectively, in the allopurinol, superoxide-dismutase, and
      hyperbaric groups. The percentage of flap necrosis was significantly smaller in
      all experimental groups when compared to controls (P < 0.05). It was clear that
      the superoxide-dismutase group had better results on axial pattern ischemic skin
      flap survival, under the tested conditions. The tested methods improved flap
      survival to ischemic injury, and the flap designed is a reliable model for
      further investigations.

PMID- 12497573
TI  - Protective effects of immunosuppressants and steroids against ischemia
      reperfusion injury in cremaster muscle flap at microcirculatory level.
AB  - The sequential events between leukocytes and endothelium have significant
      implications in surgical procedures, trauma, vascular injury, and wound healing.
      These sequential events are mediated by free oxygen radicals, leukocytes, red
      blood cells, and endothelial cells. In this study, we investigated the protective
      effects of steroids and immunosuppressants against ischemia-reperfusion injury in
      cremaster muscle flaps at the microcirculatory level. In this experimental study,
      50 male Sprague-Dawley rats, weighing about 120-130 g, were used. The rats were
      divided into five groups of 10 rats each: the control group (group 1, n = 10),
      methyl prednisolone group (group 2, n = 10), dexamethasone group (group 3, n =
      10), cyclosporin A group (group 4, n = 10), and azathioprine (group 5, n = 10).
      Surgical procedures were divided into two stages. In the first stage, a cremaster
      muscle end-organ tube flap was created by extracting the testes and spermatic
      cord. The flap was placed into a subcutaneous tunnel in the anteromedial aspect
      of the ipsilateral limb. In the experimental groups, ischemia was performed by
      clamping the femoral artery and vein above and below the cremaster pedicle for 4
      h. Then the clamps were removed, and perfusion of the cremaster muscle was
      allowed for 24 h. In the second stage, a round flap was obtained from the
      cremaster muscle tube-flap to evaluate microcirculation after 24 h of
      reperfusion, and dissected along its front wall using cauterization. Vessel
      diameter, red blood cell velocities, leukocyte activation, perfused capillaries,
      and endothelial edema index were measured and evaluated statistically. There was
      a significant decrease in the number of rolling, sticking, and transmigrating
      neutrophils of groups 2 (cyclosporin A), 4 (methylprednisolone), and 3
      (azathioprine) (P < 0.05), whereas those of group 5 (dexamethasone) were not
      decreased (P > 0.05). There was a significant increase in the number of perfused
      capillaries of groups 2 (cyclosporin A), 4 (methylprednisolone), and 3
      (azathioprine) (P < 0.05), nearly 0.75-, 0.5-, and 0.75-fold, respectively. We
      conclude that cyclosporin and azathioprine showed a protective effect on muscle
      tissue against ischemia-reperfusion injury by inhibiting leukocyte infiltration,
      and that methylprednisolone had a beneficial effect against ischemia-reperfusion
      injury by reducing the synthesis of eicosanoids, edema formation, and leukocyte
      infiltration. However, we believe that dexamethasone might have a salutary effect
      due to reducing the synthesis of eicosanoids, edema formation, and release of
      free oxygen radicals, but not due to leukocyte infiltration.

PMID- 12497574
TI  - Hypertrophy after free vascularized fibular transfer to the lower limb.
AB  - This study included 25 patients with lower limb tumors who had reconstruction by
      vascularized fibula osteoseptocutaneous flap performed at least 24 months before
      the end of the study. Hypertrophy of the transplanted fibula was estimated on
      serial radiographs by a modification of the formula of De Boer and Wood (J Bone
      Joint Surg [Br] 71:374-378, 1989). A significant graft was observed in 90% of the
      patients at an average follow-up of 27 months (range, 30-200%). The time to graft
      union (start of partial weight-bearing) positively correlated with the time to
      significant graft hypertrophy (r = 0.9, P < 0.01). The final amount of graft
      hypertrophy was affected by the age of the patient (P < 0.01) and the length of
      follow-up (P < 0.05). Graft hypertrophy progressed at an average rate of 3.3% per
      month (range, 2.3-4.9%) until the end of the 30th month; thereafter, little or no
      increase in graft hypertrophy was observed. The rate of graft hypertrophy showed
      two significant peaks at 6-12 months (P < 0.001) and at 18-24 months (P < 0.05).
      Patients younger than age 20 years showed faster hypertrophy, with a peak at the
      12th month. Hypertrophy progressed faster in patients who received chemotherapy
      until the 12th month, and then declined sharply compared to those who did not
      receive chemotherapy.

PMID- 12497575
TI  - Auxiliary partial liver grafting in rats: effect of host hepatectomy on graft
      regeneration, and review of literature on surgical technique.
AB  - Auxiliary partial liver transplantation (APLT) is beneficial for fulminant liver
      failure when there is potential for recovery of the diseased liver. However, the
      impact of host hepatectomy on regeneration of the grafted liver is unclear. In
      this study, we modified a previous rat model of auxiliary whole liver
      transplantation without portal vein reconstruction, and studied the effect of
      host hepatectomy on regeneration of the cut liver graft. Thirty percent of the
      liver was heterotopically transplanted, to connect the recipient's left renal
      artery and vein with the graft's aortic cuff of the hepatic artery and inferior
      vena cava, respectively, using a cuff technique; 30% of the recipient liver then
      was cut. The control group was left intact. The liver grafts were weighed
      preoperatively and 2 weeks postoperatively. This procedure prevented congestion
      of the graft liver and achieved a high success rate, even when performed by a
      surgeon who was relatively inexperienced with the technique. The weight of the
      grafted liver in the host hepatectomized group significantly increased (P < 0.05)
      compared with that of the control group. We developed an experimental model of
      APLT and reviewed the literature on rat heterotopic liver transplantation, and
      compared the surgical techniques.

PMID- 12497576
TI  - Biochemical evaluation of serum and flexor tenosynovium in carpal tunnel
      syndrome.
AB  - In total, 41 consecutive patients with "idiopathic carpal tunnel syndrome" and
      abnormal electrophysiologic findings who underwent carpal tunnel release were
      studied prospectively. The focus of this investigation was the evaluation of the
      levels of specific chemical mediators within the serum and flexor tenosynovium of
      these patients. Blood was collected from these patients within 1 week prior to
      carpal tunnel release, and flexor tenosynovium was obtained at time of surgery.
      Specimens were then analyzed to determine the levels of interleukins 1 and 6,
      prostaglandin E(2) (PGE(2)), and malondialdehyde bis diethyl acetal. These values
      were compared to those of controls who had no evidence of carpal tunnel syndrome.
      A significant increase was noted in the serum malondialdehyde and tenosynovial
      levels of malondialdehyde, interleukin 6, and prostaglandin PGE(2) compared to
      controls. The elevated levels of these biologic factors and the absence of
      interleukin 1 elevation support a noninflammatory ischemia-reperfusion etiology
      for so-called "idiopathic carpal tunnel syndrome" that causes progressive edema
      and fibrosis of the tissues within the carpal canal. These findings correlate
      with previous histopathology reports. We believe that "idiopathic carpal tunnel
      syndrome" is an "-osis" not an "-itis."

PMID- 12497577
TI  - Rapid neurorrhaphy with titanium clips.
AB  - The purpose of this study was to evaluate the usefulness of titanium clips in the
      repair of transected peripheral nerves. The results of neurorrhaphy using
      titanium clips (VCS) were compared with the conventional technique of
      neurorrhaphy using nylon sutures. Transected sciatic nerves in 15 New Zealand
      white rabbits were repaired with VCS clips on one side and interrupted 9-0 nylon
      sutures on the other. The average time required for neurorrhaphy using the clip
      closure was 8.7 +/- 2.6 min, and this was shorter than the suture closure, which
      took 14.9 +/- 3.6 min (P < 0.01). Electromyographic studies revealed no
      significant differences in amplitudes of compound motor action potentials in both
      groups. Also, the number and extent of myelinizations of regenerated axons were
      not significantly different in both methods of nerorrhaphies. These results
      demonstrate that microscopic neurorrhaphy using titanium clips is a potential
      alternative to conventional neurorrhaphy using sutures.

PMID- 12497579
TI  - Another tool in microsurgery: Tsai loupes.

PMID- 12497578
TI  - Management of flaps with compromised venous outflow in head and neck
      microsurgical reconstruction.
AB  - Microvascular tissue transfer has become an indispensable procedure for head and
      neck reconstruction. Although remarkable progress has been made technically,
      anastomosed vessel occlusion is still a serious complication. Even with
      technically skilled microsurgeons, anastomosed vessel occlusion occurs because
      the technique is not the sole prophylaxis against thrombosis in microsurgery.
      Therefore, to minimize the possibility of an unfavorable result in microsurgery,
      microsurgeons must be familiar with management options for a vascular compromised
      flap. Most investigators have agreed that venous obstruction occurs more often
      than arterial obstruction. Here, we reviewed the published literature on the
      salvage of venous compromised flaps from the viewpoints of surgical correction,
      including reanastomosis and catheter thrombectomy, and nonsurgical procedures,
      such as a medicinal leech, hyperbaric oxygen, and thrombolytic therapy.

PMID- 12497580
TI  - Differential expression of the estrogen receptor beta (ERbeta) in human prostate
      tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic
      adenocarcinoma.
AB  - BACKGROUND: Estrogen signaling mediated by the estrogen receptor beta (ERbeta)
      has potential implications in normal and abnormal prostate growth. Few studies
      have addressed this issue in human prostate tissue leaving conflicting results on
      the immunolocalization of the ERbeta in benign and neoplastic lesions. METHODS:
      Using a new monoclonal antibody, the current study reports on the differential
      expression of the ERbeta in tissue sections from 132 patients with prostate
      cancer. RESULTS: The prostatic epithelium expressed the ERbeta extensively in
      secretory luminal cell types and at lower levels in basal cells. Atrophic changes
      of the peripheral zone (PZ) were more immunoreactive than hyperplastic lesions of
      the transition zone (TZ). When compared with glandular tissue of the PZ, high
      grade prostatic intraepithelial neoplasia (HGPIN) revealed decreased levels of
      the ERbeta in 30 of 47 cases and was unreactive in six lesions. In informative
      cases with suitable internal controls, all primary tumors (n = 60), lymph node (n
      = 7), and bone metastases (n = 5) expressed the ERbeta at variable degree. No
      correlation was found between the ERbeta status, the primary Gleason grade (P =
      0.254), and the pathological stage (P = 0.157). Recurrent adenocarcinoma revealed
      markedly decreased levels in 15 of 40 cases and was ERbeta negative in five
      recurrent lesions. CONCLUSIONS: The secretory epithelium is a major target of
      ERbeta-mediated estrogen signaling in the human prostate. Its downregulation in
      HGPIN is consistent with chemopreventive effects that the ERbeta may exert on the
      prostatic epithelium. The continuous expression of the receptor protein at
      significant levels in untreated primary and metastatic adenocarcinoma indicates
      that these tumors can use estrogens through an ERbeta-mediated pathway. The
      partial loss of the ERbeta in recurrent tumors after androgen-deprivation may
      reflect the androgen-dependence of ERbeta gene expression in human prostate
      cancer.

PMID- 12497581
TI  - Using splines to detect changes in PSA doubling times.
AB  - BACKGROUND: PSA doubling time (PSADT) can predict the likelihood of clinical
      progression in patients with biochemical relapse after surgery or radiation for
      prostate cancer. Changes in PSA doubling time in response to therapy may be of
      clinical or investigational significance. How does one estimate PSADT before and
      after the initiation of therapy and determine if any change is statistically
      significant or simply the result of random variation? These are the type of
      questions addressed. METHODS: Our technique uses a best-fitting spline (i.e., a
      broken-line approximation) to a graph of log PSA on time to estimate PSADTs
      before and after treatment initiation. A linear regression program is used to
      produce the fit and to evaluate the statistical significance of any change in
      PSADT. This method differs from previous methods in that it uses all the data,
      exploits the continuity of PSA at the time of treatment initiation, and allows
      one to make statistical significance statements about specific individuals.
      RESULTS: Our technique is illustrated with data from a pilot clinical trial using
      a nutritional supplement in 12 men with prostate cancer. A detailed analysis of
      the first patient shows how the data are handled, how two lines of computer code
      are sufficient to fit the spline model, and how the doubling times and
      statistical significance of a change are read from the computer output. In the
      study, 9 of 12 patients had a statistically significant increase in doubling
      time. Because the study is preliminary and used only to illustrate our method, no
      medical discussion of the study is included. The last section of the study, in
      part expository, is devoted to explaining the underlying principles for those who
      may want to know not only what to do, but why it works. CONCLUSIONS: The method
      presented here for determining changes in PSADT is both simple and broadly
      applicable. It allows the evaluation of the size and statistical significance of
      an observed change or increase in PSADT in response to therapy for prostate
      cancer. It can be done using essentially any statistical software and widely
      accepted statistical methods.

PMID- 12497582
TI  - Expression of functionally active cannabinoid receptor CB1 in the human prostate
      gland.
AB  - BACKGROUND: Cannabinoids exert a wide spectrum of effects in men including
      alterations in the reproductive system. To date, two types of cannabinoid
      receptors have been cloned in humans, namely CB(1) and CB(2) belonging to the G
      protein-coupled receptor superfamily. Although cannabinoids have functional and
      morphologic effects in the prostate gland, the expression of cannabinoid
      receptors in this tissue has never been investigated. The aim of this study was
      to analyze the expression of cannabinoid receptors in the human prostate gland
      and their regulatory effects on adenylyl cyclase activity. METHODS: To
      investigate the existence of cannabinoid receptors in prostate, we used various
      methods, including reverse transcriptase-polymerase chain reaction, Western
      blotting, and immunohistochemistry. Adenylyl cyclase activity was analyzed by
      measuring the cAMP produced by means of a competitive assay by using PKA.
      RESULTS: Both mRNA for CB(1) and the corresponding protein are expressed in the
      human prostate gland at a level comparable with the receptor expressed in
      cerebellum. The molecular mass of the protein estimated from Western blot
      analysis was 58 kDa, which is in concordance with previous data for CB(1) in
      other tissues. Immunohistochemical studies show that CB(1) is preferentially
      expressed in the epithelia of the prostate. The cannabinoid receptor expressed in
      the prostate negatively regulates adenylyl cyclase activity through a pertussis
      toxin-sensitive protein.

PMID- 12497583
TI  - Clinical significance of chromosome 8p, 10q, and 16q deletions in prostate
      cancer.
AB  - BACKGROUND: We lack simple and reliable diagnostic tools to predict pathological
      staging as well as further progression of prostate cancer in individual cases.
      METHODS: We studied deletions on 8p (8p22 and 8p23-pter), 10q (10q24-qter), and
      16q (16q24) by fluorescence in situ hybridization in 53 specimens from patients
      with prostate cancer, and compared the status of these deletions with various
      clinical parameters. Forty-five cases were further evaluated regarding disease
      progression with a median follow-up period of 62 months. RESULTS: The overall
      frequencies of deletions for 8p, 10q, and 16q were 74, 55, and 55%, respectively.
      The frequency of 8p and 16q deletions increased significantly in parallel with
      tumor grade (P < 0.01 and < 0.05, respectively), while that of 10q deletions did
      not. Patients whose tumors showed 8p22 deletions had a significantly higher
      frequency in pT3 or metastatic tumors than in pT2 tumors. Patients whose tumors
      showed both 8p22 and 16q24 deletions had a significantly higher frequency of
      nodal metastases than non-metastases. A Cox hazard proportional model revealed
      8p22 deletion to be the strongest parameter predictive of disease progression
      (hazard ratio = 6.624; P = 0.0001). CONCLUSION: Estimation of 8p22 and 16q24
      deletions may serve as a genetic diagnosis for predicting pathological staging as
      well as disease progression in prostate cancer.

PMID- 12497584
TI  - Effects of bufalin and cinobufagin on the proliferation of androgen dependent and
      independent prostate cancer cells.
AB  - BACKGROUND: Cardiac glycosides may induce oncolytic effects in cancers. This
      study was to evaluate bufalin and cinobufagin effects on the proliferation of
      prostate cancer cell lines named LNCaP, DU145, and PC3. METHODS: Cell
      proliferation was measured by MTT assay. The cytotoxic effects were determined by
      lactate dehydrogenase measurements. The intracellular calcium concentration
      ([Ca(2+)](i)) was measured by a dual-wavelength spectrometer system. TUNEL assay
      and flow cytometry were performed to measure percentage of apoptotic cells. A
      colorimetric assay was to measure caspases activities. RESULTS: Bufalin and
      cinobufagin inhibited proliferation of cancer cells at doses of 0.1, 1, or 10
      microM after 2-4 days of culture. Cytotoxicity of bufalin and cinobufagin on the
      DU145 and LNCaP cells was dose-dependent. Bufalin or cinobufagin increased
      [Ca(2+)](i) and apoptosis in cancer cells after a 24-hr culture as well as
      caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP
      cells. CONCLUSIONS: Bufalin and cinobufagin may inhibit the proliferation of
      prostate cancer cell lines associated with sustained elevation of the [Ca(2+)](i)
      and that of apoptosis.

PMID- 12497585
TI  - Serum insulin-like growth factor binding protein-3/prostate-specific antigen
      ratio is a useful predictive marker in patients with advanced prostate cancer.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor
      binding protein-3 (IGFBP-3) play an important role in regulation of prostate
      cancer cell growth. We studied the prognostic significance of serum IGF-1 and
      IGFBP-3 levels, and IGF-1/prostate-specific antigen (PSA) and IGFBP-3/PSA ratios
      in patients with prostate cancer. METHODS: Serum levels of IGF-1, IGFBP-3, and
      PSA were determined in 112 patients diagnosed with prostate cancer. Serum samples
      from 32 patients with histologically confined benign prostatatic hyperplasia
      (BPH) served as control. RESULTS: Serum IGF-1 levels were significantly higher in
      advanced prostate cancer (n = 84) than in BPH patients (P < 0.01). IGFBP-3 levels
      were significantly lower in patients with advanced prostate cancer than in
      localized tumor (n = 28) or BPH (P < 0.05, each). Univariate analysis showed that
      serum PSA, IGF-1/PSA ratio, IGFBP-3/PSA ratio, T, N and M classifications
      correlated significantly with relapse-free survival of advanced prostate cancer
      patients treated with hormonal therapy. Multivariate analysis identified IGFBP
      3/PSA ratio as the only significant variable for relapse-free survival (odds
      ratio 5.81, 95% CI 1.57-21.51). IGFBP-3/PSA ratio was also an independent
      predictor of cause-specific survival (stepwise analysis, odds ratio 4.86, P <
      0.01). CONCLUSIONS: Our results suggested that IGFBP-3/PSA ratio might be a
      useful prognostic marker of advanced prostate cancer.

PMID- 12497586
TI  - Ribozyme-mediated inhibition of PKCalpha sensitizes androgen-independent human
      prostate cancer cells to cisplatin-induced apoptosis.
AB  - BACKGROUND: Therapeutic strategies to target the molecular basis of hormone and
      drug resistance of prostate cancer cells are needed. Since protein kinase Calpha
      (PKCalpha) is thought to have a role in the development of the androgen
      independent phenotype of prostate cancer cells and in apoptosis suppression, the
      objective of the present study was to test whether specific inhibition of
      PKCalpha by a hammerhead ribozyme was able to sensitize androgen-independent
      prostate cancer cells the effects of apoptosis-inducing anticancer drugs.
      METHODS: An active ribozyme (PKCalphaRZ) targeting codon 4 in human PKCalpha mRNA
      was synthesized by in vitro transcription. A mutant ribozyme (PKCalphamutRZ) was
      also made by deleting G(12) from the catalytic core of the active ribozyme and
      used as a control throughout the study. The double-stranded, ribozyme-encoding
      sequences were then inserted into an expression vector under the control of the
      cytomegalovirus promoter and delivered to growing prostate cancer cells (DU145
      and PC-3) by a DOTAP-mediated transfer. A neomycin resistance gene on the vector
      was used to select ribozyme-expressing clones. The clones were analyzed for
      PKCalpha expression, sensitivity to anticancer drugs and ability to undergo drug
      induced apoptosis. RESULTS: Two DU145-derived cell clones expressing the active
      ribozyme (DURZ 2 and DURZ 12) and one clone expressing the catalytically inactive
      ribozyme (DUmutRZ) were selected for the study. DURZ 2 and DURZ 12 were
      characterized by a markedly (about 40-50%) lower PKCalpha protein level than
      parental DU145 cells, whereas no reduction in PKCalpha expression was observed in
      DUmutRZ cells. Results of cytotoxicity experiments indicated that DURZ 2 and DURZ
      12 but not DUmutRZ cells were significantly more sensitive than parental DU145
      cells to a 1 hr exposure to the mononuclear platinum compounds (cisplatin and
      oxaliplatin) and showed an increased susceptibility to undergo cisplatin-induced
      apoptosis. A significantly enhanced apoptotic response to cisplatin was also
      observed in a PC-3-derived polyclonal cell population endogenously expressing the
      active ribozyme. CONCLUSIONS: Results of the study highlight the importance of
      PKCalpha in the response of prostate cancer cells to mononuclear platinum
      compounds and indicate specific inhibition of the enzyme as a potential
      therapeutic strategy to sensitize androgen-independent prostate cancer cells to
      these drugs.

PMID- 12497587
TI  - TERE1, a novel gene affecting growth regulation in prostate carcinoma.
AB  - Recently, we isolated a ubiquitously expressed gene designated TERE1, which has a
      significant effect on the growth regulation in bladder cancer. The TERE1 gene
      maps to chromosome 1p36.11-1p36.33 between the micro-satellite markers D1S2667
      and D1S434, a chromosome locus that has been identified by loss of heterozygosity
      studies as a site of a putative tumor suppressor gene or genes for multiple tumor
      types including prostate carcinoma. The expression of the TERE1 transcript and
      protein was examined in a series of thirty microdissected prostate tumors by semi
      quantitative RT/PCR and immunohistochemistry. There was a significant 61%
      decrease in the TERE1 transcript in prostate carcinoma (CaP) and a distinct loss
      of the TERE1 protein in metstatic prostate. Though a loss of heterozygosity at
      chromosome 1p36 was found in 25% of these prostate tumors, there appeared to be
      no TERE1 mutations present in these tumor samples. Induced TERE1 expression after
      transduction or transfection of TERE1 constructs into two prostate carcinoma
      (LNCaP and PC-3) cell lines significantly decreased proliferation up to 80% with
      a significant increase in the number of cells in G1. Serum factors but not DHT
      (dihydrotestosterone) appear to regulate the amount of TERE1 protein in the
      androgen responsive LNCaP cell line. Additionally, we have identified by
      microarray analysis various growth regulatory genes that are down-regulated or up
      regulated in TERE1-transduced PC-3 cells. Altogether, these data suggest that
      TERE1 maybe significant in prostate cancer growth regulation and the down
      regulation or absence of TERE1 may be an important component of the phenotype of
      advanced disease.

PMID- 12497588
TI  - Ionic and pharmacologic characteristics of epithelial cells in a semi-intact
      preparation of the rat ventral prostate gland.
AB  - BACKGROUND: The essential ionic and pharmacologic characteristics of epithelial
      cells within the ducts of the prostate gland are not well known. METHODS:
      Experiments were carried out on segments of ventral prostate glands from adult
      male rats. By using sharp microelectrodes, intracellular epithelial cell and
      transepithelial (lumen) potentials were recorded in response to ionic
      substitution and application of ion channel blockers, hormones, and other
      pharmacologic agents related to prostatic function. RESULTS: Membrane
      permeabilities to K(+), Na(+), and Cl(-) were found to account for approximately
      43% of the resting membrane potential, whereas some 39% was likely to be
      metabolic in origin. The membrane potential also responded to adrenaline,
      acetylcholine, insulin, prolactin, testosterone, nerve growth factor, and nitric
      oxide. The lumen potential was found to be particularly sensitive to citrate,
      prolactin, and testosterone. CONCLUSION: It was concluded that the basal membrane
      potential of prostatic epithelial cells is associated with a relatively high
      Na(+):K(+) permeability ratio and metabolic dependence. The hormonal and
      pharmacologic sensitivity observed is consistent with the functional
      characteristics of the prostate gland.

PMID- 12497589
TI  - Multicenter clinical experience with flow cytometric method for fetomaternal
      hemorrhage detection.
AB  - BACKGROUND: Enumeration of fetal red blood cells (RBCs) is important in the
      management of fetomaternal hemorrhage (FMH), particularly in situations of Rh
      incompatibility. METHODS: We evaluated results from three institutions using the
      flow cytometric method (FCM) to detect fetal RBCs based on the anti-hemoglobin F
      (HbF) monoclonal antibody method. RESULTS: During 1997-2001, 69 of 1248 patients
      (5.5%) had measurable fetal erythrocytes (RBCs) in maternal blood. Only 21
      patients (1.7%) had more than 30 mL of fetal blood detected in maternal blood. Of
      the 11 patients with large FMH and clinical follow-up, 7 had fetal demise (64%).
      In positive samples, significant differences were found in the fluorescence
      intensity (FI) of anti-HbF antibody staining between HbF-negative erythrocytes
      (HbF-) and adult HbF containing erythrocytes (F cells; 4 +/- 0 versus 57 +/- 9
      linear mean channels [LMC]; P < 0.001) and between HbF-cells and fetal RBCs (4 +/
      0 versus 433 +/- 136 LMC; P < 0.001). In addition, significant differences were
      observed in forward light scatter intensity between HbF-cells and fetal RBCs (298
      +/- 15 versus 355 +/- 68 LMC, P = 0.03). The transportability of the test is also
      addressed by comparing results from two other laboratories. The experience of our
      three laboratories, as well as the results from the recently reinitiated College
      of American Pathologists survey, which compares FCM and manual methods, clearly
      documents the superiority of the FCM test over the manual Kleihauer-Betke (KB)
      test. CONCLUSIONS: The FCM is a simpler, more objective, and more precise
      alternative to the KB method in clinical testing. The high mortality rate
      associated with large FMH and therapeutic implications of these results should
      give laboratories motivation to abandon the KB method with more robust FCM to
      detect FMH.

PMID- 12497590
TI  - Determination of bronchoalveolar lavage leukocyte populations by flow cytometry
      in patients investigated for respiratory disease.
AB  - BACKGROUND: Characteristic changes in the proportions of leukocyte populations in
      bronchoalveolar lavage (BAL) reflect different disease states in the lung. The
      standard method for examination of BAL leukocytes is by microscopy of cytospin
      preparations. This method may not be the optimum technique due to difficulties in
      distinguishing cell types morphologically and due to the low number of cells
      routinely counted. We hypothesized that flow cytometry (FCM) may be a more
      precise tool for investigating BAL. METHODS: 100 BALs were performed on 92
      patients. All samples were stained using the pan-leukocyte marker (CD45) in
      combination with a granulocyte marker (CD15) and a cell viability marker (7
      aminoactinomycin D). Selected samples were also stained with an eosinophil marker
      (CD23). These samples were run on an FCM and the results compared with leukocyte
      differentials obtained by light microscopy of parallel cytospin preparations.
      RESULTS: Close correlations between the two methods were demonstrated for the
      enumeration of all leukocyte subsets, but the coefficient of variation was
      considerably lower by FCM than by cytospin. CONCLUSIONS: These findings, combined
      with the speed of FCM and the ability to perform simple lymphocyte phenotyping,
      argue in favor of this becoming the method of choice for investigating BAL.

PMID- 12497591
TI  - Flow cytometric immunophenotyping test for staging/monitoring neuroblastoma
      patients.
AB  - Ten years ago, we made an incidental flow cytometric observation while
      immunophenotyping biopsy and marrow samples from children suspected to have
      leukemia/non-Hodgkin's lymphoma, but were subsequently diagnosed with
      neuroblastoma. The samples contained neoplastic CD45(-) cells that had an
      extremely bright CD56(+) (beyond the fourth decade on a four-decade scale)
      population distinguishable from CD45(+)CD56(usual density+) natural killer
      lymphocytes as well as other CD45(-)CD56(usual density+) nonhematopoietic tumors
      such as small cell carcinoma or melanoma. Following the "rare event" philosophy
      of selecting one negative and two positive antigens, we initially tried a
      "cocktail" of CD45(-)CD56(very bright+) neuron-specific enolase
      (NSE)(cytoplasmic+). We later modified the procedure to a more clinically
      applicable "lysed whole blood" CD45(-)CD56(very bright+) ganglioside GD2(+)
      cocktail to improve turnaround time (eliminating the cell permeabilization step
      for cytoplasmic NSE analysis), specificity, and sensitivity of the assay. A total
      of 123 marrow/tissue/fluid samples were analyzed by the various forms of the
      assay. Clearly interpretable samples had an 83% specificity and a 100%
      sensitivity. The three-color GD2 assay has successfully detected cells in marrow
      samples to a level of 0.002% (1 per 10(5) cells) using patient samples (not
      artificially "spiked" material). We added CD81 expression of the neuroblastoma
      cells as a fourth color and now use this rare event clinical test to help stage
      and monitor all patients with neuroblastoma.

PMID- 12497592
TI  - Flow cytometric-based isolation of nucleated erythroid cells during maturation:
      an approach to cell surface antigen studies.
AB  - Nucleated red blood cells (NRBCs) are involved in normal physiologic processes,
      as well as in several malignancies. They are usually counted manually under the
      microscope. However, blood sample manipulation may be a source of variability and
      manual counting is imprecise, time-consuming, and subjective. To improve
      identification of CD45-negative cells, we used a flow cytometry technique that
      avoids the addition of lysing reagents and stains viable cell nuclei. We applied
      this method for counting and isolating NRBC subpopulations in whole blood
      samples, using DNA/RNA viable staining to discriminate nonnucleated erythroid
      cells and debris. NRBC counts gave 197.95 cells per mm(3) in mobilized peripheral
      blood samples (1.00%, n = 20), 3897.59 cells per mm(3) in leukapheresis products
      (3.08%, n = 20), and 765.21 cells per mm(3) in cord blood samples (6.09%, n =
      20). Normal bone marrow counts were 5449.42 cells per mm(3) (11.76%, n = 20).
      Scatter profiles showed three distinct populations, from early to late-stage
      erythroblasts, consisting of erythroblasts, orthochromatic erythroblasts, and
      ejected nuclei, as confirmed by Wright-Giemsa staining. In addition, flow
      cytometry immunophenotyping showed that glycophorin A was expressed dimly on
      NRBCs during maturation. These findings point to the feasibility of live NRBCs
      studies, which offer great potential for a wide range of disciplines.

PMID- 12497593
TI  - Measurement of the distribution of red blood cell deformability using an
      automated rheoscope.
AB  - BACKGROUND: Red blood cells (RBCs) have to deform markedly to pass through the
      smallest capillaries of the microcirculation. Techniques for measuring RBC
      deformability often result in an indication of the mean value. A deformability
      distribution would be more useful for studying diseases that are marked by
      subpopulations of less deformable cells because even small fractions of rigid
      cells can cause circulatory problems. METHODS: We present an automated rheoscope
      that uses advanced image analysis techniques to determine a RBC deformability
      distribution (RBC-DD) by analyzing a large number of individual cells in shear
      flow. The sensitivity was measured from density-separated fractions of one blood
      sample and from cells rendered less deformable by heat treatment. A preliminary
      experiment included the RBC-DDs of a patient with sickle cell anemia, one on
      dialysis and being treated with erythropoietin, and one with elliptocytosis.
      RESULTS: Measurement of the RBC-DD was highly reproducible. The sensitivity test
      showed markedly different deformability distributions of density-separated cells
      and yielded distinct RBC-DDs after each additional minute of heat treatment.
      CONCLUSION: The automated rheoscope enabled the determination of RBC-DDs from
      which less deformable subpopulations can be established. The shape of an RBC-DD
      may be valuable in assessing cell fractions with normal and anomalous
      deformability within pathologic blood samples.

PMID- 12497594
TI  - An ab initio force field for the cofactors of bacterial photosynthesis.
AB  - This article presents a new ab initio force field for the cofactors of bacterial
      photosynthesis, namely quinones and bacteriochlorophylls. The parameters has been
      designed to be suitable for molecular dynamics simulations of photosynthetic
      proteins by being compatible with the AMBER force field. To our knowledge, this
      is the first force field for photosynthetic cofactors based on a reliable set of
      ab initio density functional reference data for methyl bacteriochlorophyll a,
      methyl bacteriopheophytin a, and of a derivative of ubiquinone. Indeed, the new
      molecular mechanics force field is able to reproduce very well not only the
      experimental and ab initio structural properties and the vibrational spectra of
      the molecules, but also the eigenvectors of the molecular normal modes. For this
      reason it might also be helpful to understand vibrational spectroscopy results
      obtained on reaction center proteins.

PMID- 12497595
TI  - Structural and dynamical analysis of the hydration of the Alzheimer's beta
      amyloid peptide.
AB  - An analysis of the water molecules in the first solvation shell obtained from the
      molecular dynamics simulation of the amyloid beta(10-35)NH2 peptide and the
      amyloid beta(10-35)NH2E22Q "Dutch" mutant peptide is presented. The structure,
      energetics, and dynamics of water in the hydration shell have been investigated
      using a variety of measures, including the hydrogen bond network, the water
      residence times for all the peptide residues, the diffusion constant,
      experimentally determined HN amide proton exchange, and the transition
      probabilities for water to move from one residue to another or into the bulk. The
      results of the study indicate that: (1) the water molecules at the peptide
      solvent interface are organized in an ordered structure similar for the two
      peptide systems but different from that of the bulk, (2) the peptide structure
      inhibits diffusion perpendicular to the peptide surface by a factor of 3 to 5
      relative to diffusion parallel to the peptide surface, which is comparable to
      diffusion of bulk water, (3) water in the first solvation shell shows dynamical
      relaxation on fast (1-2 ps) and slow (10-40 ps) time scales, (4) a novel solvent
      relaxation master equation is shown to capture the details of the fast relaxation
      of water in the peptide's first solvation shell, (5) the interaction between the
      peptide and the solvent is stronger in the wild type than in the E22Q mutant
      peptide, in agreement with earlier results obtained from computer simulations
      [Massi, F.; Straub, J. E. Biophys J 2001, 81, 697] correlated with the observed
      enhanced activity of the E22Q mutant peptide.

PMID- 12497596
TI  - Parallel stored-integral and semidirect Hartree-Fock and DFT methods with data
      compression.
AB  - Recent developments in magnetic disk technology have made stored-integral
      techniques competitive with the currently more widely used direct methods, which
      involve the recalculation of the basic two-electron integrals. We present
      efficient conventional (all integrals stored) and semidirect Hartree-Fock and DFT
      algorithms with data compression for single-processor and distributed memory
      parallel computers, and compare them with the corresponding direct algorithms. On
      inexpensive modern personal computer-based hardware, the stored integral method
      is up to three times more efficient than the direct method in terms of total
      elapsed job time.

PMID- 12497597
TI  - Inter- and intramolecular potential for the N-formylglycinamide-water system. A
      comparison between theoretical modeling and empirical force fields.
AB  - An intramolecular NEMO potential is presented for the N-formylglycinamide
      molecule together with an intermolecular potential for the N-formylglycinamide
      water system. The intramolecular N-formylglycinamide potential can be used as a
      building block for the backbone of polypeptides and proteins. Two intramolecular
      minima have been obtained. One, denoted as C5, is stabilized by a hydrogen bonded
      five member ring, and the other, denoted as C7, corresponds to a seven membered
      ring. The interaction between one water molecule and the N-formylglycinamide
      system is also studied and compared with Hartree-Fock SCF calculations and with
      the results obtained for some of the more commonly used force fields. The
      agreement between the NEMO and SCF energies for the complexes is in general
      superior to that of the other force fields. In the C7 region the surfaces
      obtained from the intramolecular part of the commonly used force fields are too
      flat compared to the NEMO potential and the ab initio calculations. We further
      analyze the possibility of using a charge distribution obtained from one
      conformation to describe the charge distribution of other conformations. We have
      found that the use of polarizabilities and generic dipoles can model most of the
      changes in charge density due to the different geometry of the new conformations,
      but that one can expect additional errors in the interaction energies that are of
      the order of 1 kcal/mol.

PMID- 12497598
TI  - Hydride transfer catalyzed by xylose isomerase: mechanism and quantum effects.
AB  - We have applied molecular dynamics umbrella-sampling simulation and ensemble
      averaged variational transition state theory with multidimensional tunneling (EA
      VTST/MT) to calculate the reaction rate of xylose-to- xylulose isomerization
      catalyzed by xylose isomerase in the presence of two Mg2+ ions. The calculations
      include determination of the free energy of activation profile and ensemble
      averaging in the transmission coefficient. The potential energy function is
      approximated by a combined QM/MM/SVB method involving PM3 for the quantum
      mechanical (QM) subsystem, CHARMM22 and TIP3P for the molecular mechanical (MM)
      environment, and a simple valence bond (SVB) local function of two bond distances
      for the hydride transfer reaction. The simulation confirms the essential features
      of a mechanism postulated on the basis of kinetics and X-ray data by Whitlow et
      al. (Whitlow, M.; Howard, A. J.; Finzel, B. C.; Poulos, T. L.; Winborne, E.;
      Gilliland, G. L. Proteins 1991, 9, 153) and Ringe, Petsko, and coworkers (Labie,
      A.; Allen, K.-N.; Petsko, G. A.; Ringe, D. Biochemistry 1994, 33, 5469). This
      mechanism involves a rate-determining 1,2-hydride shift with prior and post
      proton transfers. Inclusion of quantum mechanical vibrational energy is important
      for computing the free energy of activation, and quantum mechanical tunneling
      effects are essential for computing kinetic isotope effects (KIEs). It is found
      that 85% of the reaction proceeds by tunneling and 15% by overbarrier events. The
      computed KIE for the ratio of hydride to deuteride transfer is in good agreement
      with the experimental results. The molecular dynamics simulations reveal that
      proton and hydride transfer reactions are assisted by breathing motions of the
      mobile Mg2+ ion in the active site, providing evidence for concerted motion of
      Mg2+ during the hydride transfer step.

PMID- 12497599
TI  - Prediction of beta-sheet topology and disulfide bridges in polypeptides.
AB  - An ab initio method has been developed to predict beta architectures in
      polypeptides. The approach predicts the topology of beta-sheets and disulfide
      bridges through a novel superstructure-based mathematical framework originally
      established for chemical process synthesis problems. Two types of superstructure
      are introduced, both of which emanate from the principle that hydrophobic
      interactions drive the formation of a beta-structure. The mathematical
      formulation of the problem results in a set of integer linear programming (ILP)
      problems that can be solved to global optimality to identify the optimal beta
      configuration. These (ILP) models can also predict a ranked ordered list of the
      best, second-best, third-best, etc., topologies of beta-sheets and disulfide
      bridges. The approach is shown to perform very well for several benchmark
      polypeptide systems, as well as polypeptides exhibiting challenging nonsequential
      beta-sheet topologies folds (56 to 187 amino acids).

PMID- 12497600
TI  - Hybrid QM/MM molecular dynamics simulations for an ionic SN2 reaction in the
      supercritical water: OH- + CH3Cl --> CH3OH + Cl-.
AB  - A hybrid real space quantum mechanical/molecular mechanical (RS-QM/MM) method has
      been applied to an ionic S(N)2 reaction (OH- + CH3Cl --> CH3OH + Cl-) in water
      solution to investigate dynamic solvation effects of the supercritical water
      (SCW) on the reaction. It has been demonstrated that the approaching process of
      OH- to methyl group is prevented by water molecules in the ambient water (AW),
      while the reaction takes place easily in the gas phase. Almost the same solvation
      effect on the dynamics of OH- is observed in the SCW, though the bulk density of
      water is substantially reduced compared with that of the AW. It has been shown
      that the solvation of the SCW around the OH anion is locally identical to that of
      the AW due to the strong ion-dipole interactions between OH- and water molecules.
      At the transition state, the QM/MM simulations have revealed that the excess
      electron is quite flexible, and the charge volume, as well as the fractional
      charges on atoms, vary seriously depending on the instantaneous solvent
      configurations. However, it has been found that the solvation energy in the SCW
      can be qualitatively related to the HOMO volume of the system by Born's equation.

PMID- 12497601
TI  - An improved method for nonbonded list generation: rapid determination of near
      neighbor pairs.
AB  - Generation of the list of near-neighbor pairs of atoms not bonded to each other
      is a key feature of many programs for calculating the energy and energy
      derivatives for large molecules. Because this step can take a significant amount
      of CPU time, more efficient nonbonded list generation can speed up the energy
      calculations. In this article, a novel nonbonded list generation algorithm, BYCC,
      is introduced. It combines certain features of other algorithms and achieves more
      rapid nonbonded list generation; a factor of approximately 2.5 for a molecule of
      5000 atoms with a cutoff in the 10 A range is obtained on Hewlett-Packard (HP)
      and Alpha processors, without greatly increasing memory requirements.

PMID- 12497602
TI  - Exact rotamer optimization for protein design.
AB  - Computational methods play a central role in the rational design of novel
      proteins. The present work describes a new hybrid exact rotamer optimization
      (HERO) method that builds on previous dead-end elimination algorithms to yield
      dramatic performance enhancements. Measured on experimentally validated physical
      models, these improvements make it possible to perform previously intractable
      designs of entire protein core, surface, or boundary regions. Computational
      demonstrations include a full core design of the variable domains of the light
      and heavy chains of catalytic antibody 48G7 FAB with 74 residues and 10(128)
      conformations, a full core/boundary design of the beta1 domain of protein G with
      25 residues and 10(53) conformations, and a full surface design of the beta1
      domain of protein G with 27 residues and 10(60) conformations. In addition, a
      full sequence design of the beta1 domain of protein G is used to demonstrate the
      strong dependence of algorithm performance on the exact form of the potential
      function and the fidelity of the rotamer library. These results emphasize that
      search algorithm performance for protein design can only be meaningfully
      evaluated on physical models that have been subjected to experimental scrutiny.
      The new algorithm greatly facilitates ongoing efforts to engineer increasingly
      complex protein features.

PMID- 12497603
TI  - Computational study of epoxy-amine reactions.
AB  - Density functional theory calculations were carried out for the title reactions.
      Ethylene oxide and methylamine were adopted as reactants. Amine clusters (dimer,
      trimer, tetramer, and pentamer) were considered, because the combination of one
      oxide and one amine molecule gave a large activation energy. An amine tetramer
      was found to react favorably with the oxide via various zwitterionic
      intermediates. A back-side S(N)2 nucleophilic attack of one amine and the
      subsequent proton relay up to the front side provide a stabilized reaction field.
      The amine-alcohol mixed reactant may react readily with the oxide, because the
      alcoholic O-H group is in contact with the oxide oxygen with the strong hydrogen
      bond stabilization.

PMID- 12497604
TI  - ICFF: a new method to incorporate implicit flexibility into an internal
      coordinate force field.
AB  - We introduce a new method to accurately "project" a Cartesian force field onto an
      internal coordinate molecular model with fixed-bond geometry. The algorithm
      automatically generates the Internal Coordinate Force Field (ICFF), which is a
      close approximation of the "source" Cartesian force field. The ICFF method
      reduces the number of free variables in a model by at least 10-fold and
      facilitates the fast convergence of geometry optimizations, an advantage that is
      critical for many applications such as the docking of flexible ligands or
      conformational modeling of macromolecules. Although covalent geometry is fixed in
      an ICFF model, implicit flexibility is incorporated into the force field
      parameters in the following two ways. First, we formulate an empirical torsion
      energy term in ICFF as a sixfold Fourier series and develop a procedure to
      calculate the Fourier coefficients from the conformational energy profiles of the
      fully flexible Cartesian model. The ICFF torsion parameters thus represent not
      only torsion component of the source force field, but also bond bending, bond
      stretching, and "1-4" van der Waals interactions. Second, we use a soft
      polynomial repulsion function for "1-5" and "1-6" interactions to mimic the
      flexibility of bonds, connecting these atoms. Also, we suggest a way to use a
      local part of the Cartesian force field to automatically generate fixed covalent
      geometries, compatible with the ICFF energy function. Here, we present an
      implementation of the ICFF algorithm, which employs the MMFF94s Cartesian force
      field as a "source." Extensive benchmarking of ICFF with a representative set of
      organic molecules demonstrates that the implicit flexibility model accurately
      reproduces MMFF94s equilibrium conformational energy differences (RMSD
      approximately 0.64 kcal) and, most importantly, detailed torsion energy profiles
      (RMSD approximately 0.37 kcal). This accuracy is characteristic of the method,
      because all the ICFF parameters (except one scaling factor in the "1-5,1-6"
      repulsion term) are derived directly from the source Cartesian force field and do
      not depend on any particular molecular set. In contrast, the rigid geometry model
      with the MMFF94s energy function yields highly biased estimations in this test
      with the RMSD exceeding 1.2 kcal for the equilibrium energy comparisons and
      approximately 3.4 kcal for the torsion energy profiles.

PMID- 12497605
TI  - Selectivity of verbal memory deficit in schizophrenic patients and their
      relatives.
AB  - Some of the relatives of people with schizophrenia show impairments of memory and
      executive function. It is not known, however, whether within these domains there
      is a class of processes that is especially impaired. Seventy schizophrenic or
      schizoaffective patients, 115 of their relatives and 66 normal controls underwent
      a series of assessments evaluating modality specific recall/learning, and aspects
      of executive functioning, including, planning ability, spatial working memory,
      strategy formation and rapid mental flexibility. The pattern of performance
      across cognitive processes was assessed using z-scores that allow direct
      comparison between tests with different raw score metrics. Selectivity of deficit
      was evaluated by subtracting the z-score of each cognitive process from the mean
      of the z-scores of those remaining. Patients performed out worse than controls on
      most measures, with verbal immediate recall and visual memory/learning the most
      impaired. Their relatives showed lower scores than controls on verbal and visual
      memory/learning and strategy formation; verbal memory and strategy formation
      remained impaired after eliminating those relatives with a psychiatric diagnosis.
      Consistent with the findings in their schizophrenic kin, healthy relatives also
      showed disproportionate impairments in verbal immediate recall. Our finding of a
      selective deficit in verbal memory among relatives suggests that such impairment
      constitutes a familial, probably genetic, risk factor for schizophrenia.

PMID- 12497606
TI  - Genetic linkage and association between chromosome 1q and working memory function
      in schizophrenia.
AB  - Schizophrenia is substantially heritable, but specific susceptibility genes
      remain to be identified. Progress in this endeavor has been hindered by non
      Mendelian transmission patterns, probable genetic heterogeneity, and an inability
      to detect premorbid and nonpenetrant carriers of predisposing genes. To
      circumvent these complexities, this study employed quantitative measures of
      liability, or "endophenotypes," within a sample of twins discordant for
      schizophrenia, drawn from the relatively genetically isolated population of
      Finland. A region on the distal portion of chromosome 1 has shown evidence for
      linkage to schizophrenia in two prior studies using Finnish patient samples. To
      elucidate further the nature and location of this potential susceptibility gene,
      linkage and association analyses were carried out across the chromosome 1 region
      of interest using quantitative neuropsychological measures of liability. Analyses
      with a composite measure of liability yielded suggestive evidence for linkage at
      marker D1S2833 (P = 0.04). Follow-up analyses of the individual trait measures
      showed that the Visual Span subtest of the Wechsler Memory Scale (WMS), an
      indicator of spatial working memory function, was uniquely sensitive to marker
      D1S2833 (P = 0.007). Association analysis confirmed that allelic variation in
      D1S2833 is associated with variation in spatial working memory performance as
      measured by the Visual Span subtest (P = 0.003), the significance of which was
      confirmed in an analysis of 10,000 Monte Carlo permutations. These data support
      the utility of this approach and provide evidence for a gene affecting spatial
      working memory function in schizophrenia patients and their unaffected co-twins.

PMID- 12497607
TI  - Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype
      with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed
      across the gene region.
AB  - The glutamatergic dysfunction hypothesis suggests that genes involved in the
      glutamate neurotransmitter system are candidates for schizophrenia-susceptibility
      genes. We have been conducting systematic studies of the association between
      glutamate receptors and schizophrenia. We report on a positive association of
      some haplotypes of the AMPA receptor subunit GluR4 gene (GRIA4) with
      schizophrenia. We genotyped 100 Japanese schizophrenics and 100 controls for six
      single nucleotide polymorphism (SNP) markers distributed at intervals of about 50
      kb in the GRIA4 region, and estimated the degree of linkage disequilibrium (LD)
      between the SNPs. We constructed haplotypes of the SNPs in LD using the EM
      algorithm to test their association with schizophrenia. Significant associations
      were detected for the combination of SNP4-5 (chi(2) = 12.54, df = 3, P = 0.0057,
      P = 0.029 with Bonferroni correction) and for the combination of SNP3-4-5 (chi(2)
      = 18.9, df = 7, P = 0.0085, P = 0.043 with Bonferroni correction). These results
      suggest that at least one susceptibility locus for schizophrenia is located
      within or very close to the GRIA4 region in Japanese.

PMID- 12497608
TI  - Early-onset schizophrenia and dopamine-related gene polymorphism.
AB  - Schizophrenic patients with an onset before age 16 years (early-onset
      schizophrenia, EOS) would be a rare but attractive subpopulation for genetic
      studies. This study explored the relationship between the polymorphism of four
      dopamine-regulating-enzymes (tyrosine hydroxylase, dopamine-beta-hydroxylase,
      catechol-O-methyltransferase, monoamine oxidase-A) genes, four dopamine-receptors
      (dopamine D1, D2, D3, D4 receptors) genes and susceptibility to EOS in a Japanese
      sample. Subjects comprised 51 Japanese patients who met DSM-IV criteria for
      schizophrenia with an onset before age 16 (by age 15) and 148 Japanese healthy
      controls. DNA was extracted from whole blood and genotyping was carried out by
      PCR-RELP using each restriction endonuclease. No significant difference was found
      in the allele frequencies or genotype distributions of any of the eight genes
      examined between EOS and the control groups. We did not find the relationship
      between the polymorphism of eight dopamine-related genes and susceptibility to
      EOS in a Japanese sample.

PMID- 12497609
TI  - Fine mapping of an isodicentric Y chromosomal breakpoint from a schizophrenic
      patient.
AB  - We report on a male schizophrenic patient who carried an isodicentric Y
      chromosome [idic(Y)] with a mosaic karyotype [mos 45,X/46,X,idic(Y)(q11)].
      Although a potential association between sex chromosome abnormalities and a
      susceptibility to psychoses has been documented, there has only been one previous
      report of idic(Y) coincident with schizophrenia. The [45,X] karyotype is known to
      be associated with Turner syndrome (TS), but our patient lacked most of the
      phenotypic features of TS, except for short stature. To define the precise
      position of the breakpoint on the patient's abnormal Y chromosome, we carried out
      polymerase chain reaction (PCR) analysis, using primers for 15 marker loci along
      the chromosome. The breakpoint was localized to between the marker loci sY118 and
      sY119 on Yq in the 5M interval of the deletion map. This position represents the
      most centromeric breakpoint recorded for idic(Y). We cannot exclude the
      possibility that the development of schizophrenia is unrelated to the Y
      chromosome abnormality in this patient but we hope that this study will stimulate
      further cytogenetic and molecular genetic analyses of Y chromosome regions that
      may influence psychiatric traits.

PMID- 12497610
TI  - Association study between CAG trinucleotide repeats in the PCQAP gene (PC2
      glutamine/Q-rich-associated protein) and schizophrenia.
AB  - Schizophrenia or schizoaffective disorders are quite common features in patients
      with DiGeorge/velocardiofacial syndrome (DGS/VCFS) as a result of hemizygosity of
      chromosome 22q11.2. We evaluated the PCQAP gene, which maps within the DGS/VCFS
      interval, as a potential candidate for schizophrenia susceptibility. PCQAP
      encodes for a subunit of the large multiprotein complex PC2, which exhibits a
      coactivator function in RNA polymerase II mediated transcription. Using a case
      control study, we searched association between schizophrenia and the intragenic
      coding trinucleotide polymorphism. The distribution of the CAG repeat alleles was
      significantly different between patients and controls with the Mann-Whitney test
      (z = -2.5694, P = 0.0051; schizophrenics: n = 378, W = 161,002.5, Mean rank =
      425.9325; controls: n = 444, W = 177,250.5, Mean rank = 399.2128). This result
      may indicate a possible involvement of the multiprotein complex PC2 in
      schizophrenia susceptibility.

PMID- 12497611
TI  - Generalized cognitive impairment in male adolescents with schizotypal personality
      disorder.
AB  - Schizotypal Personality Disorder (SPD) shares common genetic and biological
      substrates with schizophrenia, and patients with SPD have been reported to suffer
      both from specific cognitive impairments, and from a generalized cognitive
      dysfunction, similar to those found in schizophrenia. The aim of this cross
      sectional, population-based study was to assess general cognitive functioning in
      adolescents with SPD. The Israeli Draft Board systematically assesses cognitive
      functioning and administers psychiatric screening in all 16-17-year-old males in
      the population. Of 341,511 males assessed, the cognitive test scores of
      adolescents with SPD (N = 326) were retrieved, and compared to the scores of
      adolescents diagnosed as suffering from schizophrenia (N = 901), and adolescents
      with no neurological or psychiatric diagnosis (controls, N = 293,820). Male
      adolescents with SPD or with schizophrenia scored lower on all measures compared
      to healthy individuals (effect sizes ranging from 0.6-0.88, all P < 0.001). The
      SPD patients scored significantly higher than the schizophrenia patients on the
      sub-tests of similarities and Ravens Progressive Matrices, tests that reflect
      abstract reasoning. On the sub-tests of arithmetic and instruction comprehension,
      tests that rely on concentration, SPD and schizophrenia patients' scores did not
      differ significantly from each other. These results might be interpreted to imply
      that a generalized cognitive impairment, in the presence of schizotypal
      personality traits and in the absence of psychosis, might be conceptualized as
      being the core of the schizotaxia syndrome. The greater impairment in abstract
      reasoning in the schizophrenia patients might be correlated with the psychotic
      symptoms that differentiate schizophrenia from SPD.

PMID- 12497612
TI  - Association study between the fibronectin gene and schizophrenia.
AB  - Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an
      important role in neural and synaptic genesis, and their dysfunction may result
      in neurodevelopmental abnormalities, which have been assumed to be a factor in
      the pathogenesis of schizophrenia. To examine the possible involvement of
      fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms,
      located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human
      fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n =
      104) and age-and gender-matched controls (n = 104). No significant positive
      association was observed between either of the polymorphisms and schizophrenia,
      nor was an association found between either of the polymorphisms and any subtypes
      of schizophrenia. These data did not provide evidence for a contribution of the
      FN1 gene to susceptibility to schizophrenia.

PMID- 12497613
TI  - CAG repeat polymorphisms in KCNN3 (HSKCa3) and PPP2R2B show no association or
      linkage to schizophrenia.
AB  - The purpose of this study was to determine whether genetic linkage or association
      could be observed between schizophrenia (SZ) and the CAG repeat polymorphisms
      within the genes KCNN3 (known previously as hSKCa3) and PPP2R2B (linked to Spino
      Cerebellar Atrophy 12) in the Xhosa population in South Africa. Neither locus has
      been studied previously in African populations. The polymorphisms were genotyped
      in 589 individuals to form samples for Transmission Disequilibrium Test (TDT)
      analysis (176 unrelated probands, 145 with both parents and 30 with one parent
      genotyped), linkage analysis (49 families with 54 independent affected sib pairs
      [ASPs]), and case-control analyses (67 familial cases with a first-degree SZ
      relative, 101 sporadic cases with no affected first- or second-degree relative,
      and 90 control cases). No significant differences were found among familial
      cases, sporadic cases and controls in allele sizes (Kruskal-Wallis tests) or the
      numbers of alleles with sizes above and below the mean size for each
      polymorphism. Allele size was not correlated with age of onset (Spearman
      correlation). No significant evidence for association was observed using TDT
      analyses for all triads and separately for the familial triads. No significant
      evidence for linkage was observed for either locus with affected sib pair
      analysis using the possible triangle method or with Non-Parametric Linkage (NPL)
      analysis of the multiplex families. In conclusion, no significant evidence for
      linkage or association with SZ was observed for either polymorphism in this
      population.

PMID- 12497614
TI  - Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients
      with schizophrenia.
AB  - The putative role of dopamine in the pathophysiology of tardive dyskinesia (TD)
      makes the genes coding for dopamine receptors the appropriate candidates for
      study. We investigate the association of the polymorphism of the Ser311Cys and
      Ser9Gly of the dopamine D2 (DRD2) and D3 receptor (DRD3) genes respectively with
      TD in Chinese patients with schizophrenia. In a case-control study, 117 Chinese
      patients with TD were compared to 200 patients without TD. Patients were
      diagnosed to have schizophrenia according to DSM-IV criteria. Dyskinesia was
      assessed by the Abnormal Involuntary Movement Scale (AIMS), whereas
      extrapyramidal side-effects (EPSE) were assessed by the Simpson-Angus Rating
      Scale. Genotype groups were comparable in age, gender, duration of illness, daily
      neuroleptic and benzodiazepine dose as well as the mean scores for EPSE. We
      failed to find an association between the polymorphism of the DRD2 gene with TD
      but found an increased risk of developing TD among those with D3 serine/serine
      genotype. Our results did not indicate that the D2 genotype has a role in the
      pathophysiology of TD in Chinese patients with schizophrenia. The association of
      TD with the serine/serine genotype of the DRD3 may be an epiphenomenon of
      patients with a subtype of schizophrenia who had more exposure to neuroleptics.

PMID- 12497615
TI  - Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder.
      Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors
      are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the
      third exon of the dopamine receptor type 4 (DRD4) gene has been described.
      Previous case control studies, however, have reported inconclusive results in
      OCD. The aim of the study was to study this polymorphism in a family-based
      association study of 55 trios. Extended transmission-disequilibrium test (ETDT)
      for preferential allele transmission in this group showed an absence of
      transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene
      (P = 0.005). Moreover, in a population-based association study, we found a
      significantly lower frequency of the allele 2 in patients suffering from OCD
      compared to ethnically-matched controls (P = 0.02). We found no association of
      DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics.
      This study is the first to report on a significant association of variants of the
      DRD4 gene in OCD, found on both family- and population-based studies. The results
      suggest that the 2 allele or a nearby genetic variation could have a protective
      effect against OCD symptoms.

PMID- 12497616
TI  - Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with
      Gilles de la Tourette syndrome.
AB  - Obsessive-compulsive disorder (OCD) is an etiologically heterogeneous disorder.
      Recent factor analyses have consistently identified several symptom dimensions,
      two of which are associated with increased familial risk for OCD; aggressive,
      sexual, and religious obsessions and checking compulsions (FACTOR 1) and symmetry
      and ordering obsessions and compulsions (FACTOR 2). Both of these symptom
      dimensions are also frequently seen in association with Gilles de la Tourette
      syndrome (GTS). The purpose of this study was to determine whether these
      obsessive-compulsive (OC) symptom dimensions are correlated within families
      (between sibs and between parent-child pairs). Using data collected by the
      Tourette Syndrome Association International Consortium for Genetics Affected
      Sibling Pair Study, the authors selected all available GTS sib pairs and their
      parents for which these OC symptom dimensions (factor scores) could be generated.
      This group included 128 full sibs and their mothers (54) and fathers (54). Four
      OC symptom dimension scores were computed for each family member using an
      algorithm derived from item endorsements from the Yale-Brown Obsessive-Compulsive
      Scale (Y-BOCS) symptom checklist. In addition to a series of univariate analyses,
      complex segregation analyses were also completed using these quantitative OC
      symptom dimension scores. FACTOR 1 and FACTOR 2 scores were significantly
      correlated in sib pairs concordant for GTS. The mother-child correlations, but
      not father-child correlations, were also significant for these two factors.
      Segregation analyses were consistent with dominant major gene effects for both
      FACTOR 1 and FACTOR 2. We conclude that familial factors contribute significantly
      to OC symptom dimension phenotypes in GTS families. This familial contribution
      could be genetic or environmental.

PMID- 12497617
TI  - Lack of association between serotonin 5-HT1B receptor gene polymorphism and
      suicidal behavior.
AB  - A genetic susceptibility to suicide attempts has been repeatedly suggested by
      family-, twin-, and adoption-studies. Because elevated impulsive aggression is
      one of the most prominent characteristics of suicide attempters and aggressive
      behavior has been reported in 5-HT1B receptor gene knockout mice, the serotonin
      receptor 1B gene (5-HT1B) is an attractive candidate. The distribution of a
      polymorphism (G861C) in the 5-HT1B gene was examined in 148 consecutively
      hospitalized German suicide attempters, and 327 German healthy volunteers
      randomly recruited from the general population. The controls and their first
      degree relatives had no history of mental disorders or suicidal behavior. We
      found no significant difference in allele or genotype frequency between patients
      and controls. The results did not differ when the patients were divided into
      several subgroups (gender, suicide attempters with a violent method or suicide
      attempters with unipolar-, bipolar-, borderline personality-, and schizophrenia
      spectrum disorders). These findings suggest that the 5-HT1B polymorphism is
      unlikely to play a major role in the genetic susceptibility to suicide attempts.

PMID- 12497618
TI  - No association between non-violent suicidal behavior and the serotonin
      transporter promoter polymorphism.
AB  - There is compelling evidence that suicidal behavior is associated with the
      dysfunction of the serotonin system. A functional polymorphism in the promoter
      region of the serotonin transporter gene (5-HTTLPR) was recently identified and
      the presence of the short allele was associated with lower gene expression, lower
      5-HT uptake and violent suicidal behavior. Thus, we attempted to determine
      whether 5-HTTLPR is also involved in the susceptibility to non-violent suicidal
      behavior. We compared the genotype from 166 West European Caucasians who
      attempted suicide by a non-violent mean with 139 controls with no history of
      suicidal behavior from the same ethnic origin. The frequencies of the S allele
      and the SS genotype in the sample who attempted non-violent suicide were not
      statistically different to those in the controls. Thus, the genetically altered
      expression of the 5-HT transporter might be associated with more severe or
      violent suicidal behavior, but not with non-violent suicidal behavior.

PMID- 12497619
TI  - Polymorphism screening of PIK4CA: possible candidate gene for chromosome 22q11
      linked psychiatric disorders.
AB  - Lithium is potent non-competitive inhibitor of an enzyme involved in the
      metabolism of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P(2)), a critical
      phosphoinositide (PI) that regulates signal transduction and synaptic vesicle
      function. Interestingly, a number of genes involved in the regulation of PtdIns
      4,5-P(2) synthesis and dephosphorylation are found in regions of the genome
      previously mapped in bipolar disorder (BPD) including 10p, 18q, 21q, and 22q. One
      is PIK4CA, a member of the phosphatidylinositol 4-kinase family that
      phosphorylates PtdIns at the D4 position of the inositol ring as part of the
      PtdIns-4,5-P(2) synthetic pathway. PIK4CA maps to 22q11 in a region believed to
      contain a susceptibility gene for psychiatric disorders. Screening of two
      functional domains of PIK4CA and the promoter region resulted in the
      identification of 15 different polymorphisms. Rare variants at a consensus splice
      donor site and the promoter region were found in a total of three patients with
      BPD, three with schizophrenia (SZ) and only one control. Several common non
      synonymous changes and a common single nucleotide polymorphism (SNP) at position 
      31 in the putative promoter were identified and analyzed in patients with BPD,
      SZ, and controls. There was no difference in the allele distribution in mentally
      ill subjects and controls for two variants, R2259C and E2079Q, both located in
      the PIK4CA catalytic domain. There was, however, a trend toward significance in
      the distribution of the -31 promoter genotypes in bipolar subjects and controls.
      Although the results of this analysis were modest, considering the heterogeneity
      of BPD and SZ and the hypothesis that BPD may be caused by abnormalities in genes
      that regulate PI-mediated phenomena in the brain, the polymorphisms we detected
      in the PIK4CA gene should be analyzed in a larger data set to help determine
      their significance in 22q11-linked mental disorders.

PMID- 12497620
TI  - Association analysis of monoamine oxidase A and attention deficit hyperactivity
      disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder.
      Although the causes of ADHD are unknown, dopaminergic, serotonergic and nor
      adrenergic pathways have been strongly implicated. Monoamine Oxidase A (MAOA) is
      involved in the degradation of all three of these neurotransmitters and therefore
      has been suggested as a strong candidate gene for ADHD. Animal and human studies
      have implicated MAOA and 5-HT in impulsive and aggressive behavior. We therefore
      additionally postulated that MAOA might be associated with a subtype of ADHD
      where aggressive and impulsive features are especially prominent. We have tested
      this hypothesis by genotyping two polymorphisms (the 30-bp VNTR in the promoter
      and the Fnu4HI 941T-->G) in MAOA that are associated with altered MAOA function.
      Our sample consisted of 171 British Caucasian children 6-16 years of age
      fulfilling DSM-III R, DSM-IV or ICD-10 criteria for ADHD/Hyperkinetic Disorder.
      Using case control analysis and then the TDT, no association was found between
      these two MAOA polymorphisms and ADHD. Case control analysis of the VNTR showed
      an association with a subgroup of children with comorbid conduct problems (OR =
      2.0, 95% CI = 1.09, 3.5), and TDT analysis indicated a statistical trend toward
      association. Our findings highlight the importance of phenotype definition and
      the need for the MAOA VNTR to be further examined.

PMID- 12497621
TI  - Familial aggregation of psychotic symptoms in a replication set of 69 bipolar
      disorder pedigrees.
AB  - We found evidence previously of familial aggregation of psychotic symptoms in 65
      bipolar disorder pedigrees. This finding, together with prior evidence from
      clinical, family, neurobiological, and linkage studies, suggested that psychotic
      bipolar disorder may delineate a valid subtype. We sought to replicate this
      finding in 69 new bipolar disorder pedigrees. The presence of psychotic symptoms,
      defined as hallucinations or delusions, during an affective episode was compared
      in families of 46 psychotic and 23 non-psychotic bipolar I probands ascertained
      at Johns Hopkins for the NIMH Bipolar Disorder Genetics Initiative. There were
      198 first-degree relatives with major affective disorder including 90 with
      bipolar I disorder. Significantly more psychotic proband families than non
      psychotic proband families (76% vs. 48%) contained at least one affected relative
      with psychotic symptoms. Psychotic symptoms occurred in 35% of relatives of
      psychotic probands and in 22% of relatives of non-psychotic probands (P = 0.10).
      Both psychotic affective disorder generally and psychotic bipolar I disorder
      clustered significantly in families. These results are consistent with our prior
      report although the magnitude of the predictive effect of a psychotic proband is
      less in the replication families. Our findings provide modest support for the
      validity of psychotic bipolar disorder as a subtype of bipolar disorder. This
      clinically defined subtype may prove more homogeneous than the disorder as a
      whole at the level of genetic etiology and of neuropathology/pathophysiology.
      Families with this subtype should be used to search for susceptibility genes
      common to bipolar disorder and schizophrenia, and for biological markers that may
      be shared with schizophrenia.

PMID- 12497622
TI  - Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in
      African-Americans.
AB  - Apolipoprotein D (APOD, gene; apoD, protein) is involved in neuroregenerative and
      neurodegenerative processes, and is upregulated in late-onset Alzheimer disease
      (AD) patients compared to nondemented controls. No genetic association studies
      have yet been carried out to investigate the role of APOD in AD. We have reported
      recently several sequence variants in the APOD gene, which are present
      exclusively among African blacks. In the present study we examined the role of
      four APOD genetic variants (Intron 1, codons 36, 108, 158) in modifying the risk
      of AD in 70 subjects with AD and 163 nondemented subjects from a population-based
      African-American cohort in Indianapolis. The Intron 1*2 allele was associated
      with an increased AD risk with an age, gender and APOE adjusted odds ratio (OR)
      of 2.29 (95% confidence interval [CI]: 1.19-4.43; P = 0.013), and this risk was
      confined to APOE*4 carriers (OR 3.12; 95% CI: 1.13-8.60; P = 0.028). The
      frequency of the codon 36/GT genotype was non-significantly higher in individuals
      with AD than nondemented subjects (4.3% vs. 1.2%) with an adjusted OR of 4.24
      (95% CI: 0.66-27.14; P = 0.13). Our data suggest that the risk of AD among
      African-Americans may be modified by genetic variation in APOD. Larger population
      based or case-control studies are needed to confirm the role of APOD genetic
      variation in AD.

PMID- 12497623
TI  - The real problem in association studies.

PMID- 12497624
TI  - D2 dopamine receptor gene in psychiatric and neurologic disorders and its
      phenotypes.
AB  - The D2 dopamine receptor (DRD2) has been one of the most extensively investigated
      gene in neuropsychiatric disorders. After the first association of the TaqI A
      DRD2 minor (A1) allele with severe alcoholism in 1990, a large number of
      international studies have followed. A meta-analysis of these studies of
      Caucasians showed a significantly higher DRD2 A1 allelic frequency and prevalence
      in alcoholics when compared to controls. Variants of the DRD2 gene have also been
      associated with other addictive disorders including cocaine, nicotine and opioid
      dependence and obesity. It is hypothesized that the DRD2 is a reinforcement or
      reward gene. The DRD2 gene has also been implicated in schizophrenia,
      posttraumatic stress disorder, movement disorders and migraine. Phenotypic
      differences have been associated with DRD2 variants. These include reduced D2
      dopamine receptor numbers and diminished glucose metabolism in brains of subjects
      who carry the DRD2 A1 allele. In addition, pleiotropic effects of DRD2 variants
      have been observed in neurophysiologic, neuropsychologic, stress response,
      personality and treatment outcome characteristics. The involvement of the DRD2
      gene in certain neuropsychiatric disorders opens up the potential of a targeted
      pharmacogenomic approach to the treatment of these disorders.

PMID- 12497626
TI  - eMelanoBase: an online locus-specific variant database for familial melanoma.
AB  - A proportion of melanoma-prone individuals in both familial and non-familial
      contexts has been shown to carry inactivating mutations in either CDKN2A or,
      rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from
      alternately spliced transcripts that are read in different frames. The alpha
      transcript (exons 1alpha, 2, and 3) produces the p16INK4A cyclin-dependent kinase
      inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF,
      a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2
      can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta,
      and 2, which can theoretically generate p16INK4A-p14ARF fusion proteins. No
      online database currently takes into account all the consequences of these
      genotypes, a situation compounded by some problematic previous annotations of
      CDKN2A-related sequences and descriptions of their mutations. As an initiative of
      the international Melanoma Genetics Consortium, we have therefore established a
      database of germline variants observed in all loci implicated in familial
      melanoma susceptibility. Such a comprehensive, publicly accessible database is an
      essential foundation for research on melanoma susceptibility and its clinical
      application. Our database serves two types of data as defined by HUGO. The core
      dataset includes the nucleotide variants on the genomic and transcript levels,
      amino acid variants, and citation. The ancillary dataset includes keyword
      description of events at the transcription and translation levels and
      epidemiological data. The application that handles users' queries was designed in
      the model-view-controller architecture and was implemented in Java. The object
      relational database schema was deduced using functional dependency analysis. We
      hereby present our first functional prototype of eMelanoBase. The service is
      accessible via the URL www.wmi.usyd.edu.au:8080/melanoma.html.

PMID- 12497627
TI  - Two cases of misinterpretation of molecular results in incontinentia pigmenti,
      and a PCR-based method to discriminate NEMO/IKKgamma dene deletion.
AB  - Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that
      affects ectodermal tissues. Over 90% of IP carrier females have a recurrent
      genomic deletion of exons 4-10 of the NEMO (IKBKG-IKKgamma) gene, which encodes a
      regulatory component of the IkB kinase complex, required to activate the NF-kB
      pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation
      creating a susceptibility to cellular apoptosis in response to TNF-alpha. This
      condition is lethal for males during embryogenesis while females, who are mosaic
      as a result of X-inactivation, can survive. Recently, a second nonfunctional copy
      of the gene, DeltaNEMO, was identified, opposite in direction to NEMO in a 35.5
      kb duplicated sequence tract. PCR-based detection of the NEMO deletion is
      diagnostic for IP disease. However, we present instances in which ex 4-10
      DeltaNEMO pseudogene deletion occurs in unaffected parents of two females with
      clinically characteristic IP. These were missed by the currently standard PCR
      based method, but can be easily discriminated by a new PCR-based test reported
      here that permits unambiguous molecular diagnosis and proper familial genetic
      counseling for IP.

PMID- 12497628
TI  - Direct estimates of human per nucleotide mutation rates at 20 loci causing
      Mendelian diseases.
AB  - I estimate per nucleotide rates of spontaneous mutations of different kinds in
      humans directly from the data on per locus mutation rates and on sequences of de
      novo nonsense nucleotide substitutions, deletions, insertions, and complex events
      at eight loci causing autosomal dominant diseases and 12 loci causing X-linked
      diseases. The results are in good agreement with indirect estimates, obtained by
      comparison of orthologous human and chimpanzee pseudogenes. The average direct
      estimate of the combined rate of all mutations is 1.8x10(-8) per nucleotide per
      generation, and the coefficient of variation of this rate across the 20 loci is
      0.53. Single nucleotide substitutions are approximately 25 times more common than
      all other mutations, deletions are approximately three times more common than
      insertions, complex mutations are very rare, and CpG context increases
      substitution rates by an order of magnitude. There is only a moderate tendency
      for loci with high per locus mutation rates to also have higher per nucleotide
      substitution rates, and per nucleotide rates of deletions and insertions are
      statistically independent on the per locus mutation rate. Rates of different
      kinds of mutations are strongly correlated across loci. Mutational hot spots with
      per nucleotide rates above 5x10(-7) make only a minor contribution to human
      mutation. In the next decade, direct measurements will produce a rather precise,
      quantitative description of human spontaneous mutation at the DNA level.

PMID- 12497629
TI  - Meta-analysis of indels causing human genetic disease: mechanisms of mutagenesis
      and the role of local DNA sequence complexity.
AB  - A relatively rare type of mutation causing human genetic disease is the indel, a
      complex lesion that appears to represent a combination of micro-deletion and
      micro-insertion. In the absence of meta-analytical studies of indels, the
      mutational mechanisms underlying indel formation remain unclear. Data from the
      Human Gene Mutation Database (HGMD) were therefore used to compare and contrast
      211 different indels underlying genetic disease in an attempt to deduce the
      processes responsible for their genesis. Each indel was treated as if it were the
      result of a two-step insertion/deletion process and was assessed in the context
      of 10 base-pairs DNA sequence flanking the lesion on either side. Several indel
      hotspots were noted and a GTAAGT motif was found to be significantly over
      represented in the vicinity of the indels studied. Previously postulated
      mechanisms underlying micro-deletions and micro-insertions were initially
      explored in terms of local DNA sequence regularity as measured by its complexity.
      The change in complexity consequent to a mutation was found to be indicative of
      the type of repeat sequence involved in mediating the event, thereby providing
      clues as to the underlying mutational mechanism. Complexity analysis was then
      employed to examine the possible intermediates through which each indel could
      have occurred and to propose likely mechanisms and pathways for indel generation
      on an individual basis. Manual analysis served to confirm that the majority of
      indels (>90%) are explicable in terms of a two-step process involving established
      mutational mechanisms. Indels equivalent to double base-pair substitutions (22%
      of the total) were found to be mechanistically indistinguishable from the
      remainder and may therefore be regarded as a special type of indel. The observed
      correspondence between changes in local DNA sequence complexity and the
      involvement of specific mutational mechanisms in the insertion/deletion process,
      and the ability of generated models to account for both the number and identity
      of the bases deleted and/or inserted, makes this approach invaluable not only for
      the analysis of indel formation, but also for the study of other types of complex
      lesion.

PMID- 12497630
TI  - Sequence diversity of KIAA0027/MLC1: are megalencephalic leukoencephalopathy and
      schizophrenia allelic disorders?
AB  - The aim of the study is to validate the etiological role of KIAA0027/MLC1 in
      childhood-onset megalencephalic leukoencephalopathy with subcortical cysts (MLC)
      and in schizophrenia, particularly the catatonic subtype, which were reported to
      be allelic diseases. Among a series of five patients with MLC, four mutant
      alleles were detected: one case of compound heterozygosity for a splice site
      mutation and a six-base-pair in-frame deletion, one patient with a homozygous
      frameshifting insertion-deletion, and a further case heterozygous for a A157E
      substitution. A systematic mutation screening in 140 index cases with
      schizophrenia revealed 13 different single nucleotide polymorphisms (SNPs): one
      SNP in the 5'-UTR, seven SNPs in intronic regions, two synonymous codon variants
      (T52, Y199), and three coding variants. Two of them, C171F and N218K, were
      observed in controls at a significant frequency. The L309M variant that was
      previously supposed to be the causative factor for chromosome 22q(tel) linked
      periodic catatonia was found nonsegregating in a further multiplex pedigree.
      Furthermore, a complicated 33-bp insertion/deletion polymorphism at the 5'-end of
      exon 11 of MLC1 was found at equal frequency among schizophrenic patients and
      controls. In summary, our study provides further evidence for allelic
      heterogeneity in megalencephalic leukoencephalopathy, excludes MLC1 as a
      susceptibility locus for schizophrenia, and thereby rules out that MLC and
      schizophrenia are allelic disorders.

PMID- 12497631
TI  - Further evidence for role of a promoter variant in the TNFRSF6 gene in Alzheimer
      disease.
AB  - The tumor necrosis factor receptor superfamily, member 6 gene (TNFRSF6) is
      situated on chromosome 10q, near the region indicated in several AD linkage
      studies. In a previous study a significant association was found between a
      promoter variant within the TNFRSF6 gene and Alzheimer disease (AD). To further
      investigate the TNFRSF6 region, 34 SNPs within 180 kb were first genotyped in an
      exploratory set of 121 early-onset dementia cases and 152 controls in order to
      establish the extent of linkage disequilibrium (LD) and the major haplotypes in
      the region. This analysis showed that the LD was clustered in two large blocks
      within each of which a limited number of haplotypes represented most of the
      diversity. Haplotype tagging markers were chosen and genotyped in an additional
      204 late onset AD cases and 177 controls. Tests of association were performed for
      single markers for case/control status and for a quantitative measure of
      cognitive ability [Mini-Mental State Examination (MMSE) scores] within cases
      only. The previously associated marker, located in the promoter of TNFRSF6, now
      gave significant association with cognitive status in the Scottish early-onset
      dementia samples (p = 0.005) with the strongest signals being evident in the APOE
      e4 carrier subgroup, thus providing a second independent positive result for this
      marker. The same marker was also significantly associated with cognitive
      performance in the Swedish APOE-e4 carriers (p = 0.014), providing a third
      independent signal. Association analysis was also performed using the major
      haplotypes in the region, employing both case/control status and MMSE scores. The
      haplotype analysis did not give further significant findings. These results
      together with previous data suggest that a promoter marker in TNFRSF6 plays a
      moderate but demonstrable role in AD etiology.

PMID- 12497632
TI  - Dynamics of CAG repeat loci revealed by the analysis of their variability.
AB  - In order to understand the dynamics of the expressed single tandem repeat
      trinucleotides (most of them involved in pathological expansion), the diversity
      in 10 different loci (SCA1, SCA2, SCA3, SCA6, SCA8, SCA12, DRPLA, HD, KCNN3, and
      NCOA3) was analyzed in four major human groups (Africans, Europeans, Indians, and
      East Asians). The present analysis intends to disentangle population-based from
      genetic-based factors having shaped STR (trinucleotide) variation and to
      recognize, for each locus, the specific rate and pattern of mutation (bias toward
      expansion or contraction, constraints on allele size), and the footprints of
      selection. Population differences account for a very small part of the total
      variation, but a clear footprint appears of population growth after a bottleneck
      in all non-African populations, giving support to the out-of-Africa model of
      modern humans. Most of the diversity is found among loci, and different dynamics
      are inferred for each of them. SCA2 and SCA3 follow an unrestricted stepwise
      mutation model, while the rest of loci are found under allele size constrictions
      and a bias to expansion (SCA1, SCA6, HD, and KCNN3), contraction (SCA12, DRPLA,
      and NCOA3), or unbiased (SCA8).

PMID- 12497633
TI  - The mutational spectrum of human autosomal tetranucleotide microsatellites.
AB  - We studied by multiplex amplification and single-run electrophoretic analysis 10
      microsatellite loci, composed of nine tetranucleotide-repeats (D1S1612, D3S2387,
      D4S2431, D5S2501, D10S1237, D15S657, D16S2622, D18S1270, and IFNAR-ALU) and one
      trinucleotide repeat (D2S1353). After elimination of proven null allele events
      involving D1S1612 and D5S2501 and of all data of D3S2387, in which we suspected
      but could not prove the occurrence of null alleles, we were left with nine loci,
      encompassing 24,224 meioses and 23 mutations. Twenty-two of the mutations (96%)
      were single-step events. Moreover, 18 of the mutations were paternal, four were
      maternal, and one was indeterminate. There was no significant difference between
      the number of additions and deletions in the mutants. Our findings are compatible
      with a simple model in which tetranucleotide microsatellites mutate primarily in
      paternal germinative cells by DNA slippage, such that the vast majority of
      mutations are equiprobable additions or deletions of a single-repeat unit. By
      combining the data from our tetranucleotide loci with literature information of
      highly and lowly mutable microsatellites, we observed a very highly significant
      correlation between mutation rate and the geometric mean of the length of the
      longest perfect repeat region (LRPR), compatible with a power or exponential
      relationship. The variation of the length of the LRPR explained as much as 80% of
      the variance of the mutation rate of autosomal tetranucleotide microsatellites.

PMID- 12497634
TI  - ATM mutations on distinct SNP and STR haplotypes in ataxia-telangiectasia
      patients of differing ethnicities reveal ancestral founder effects.
AB  - Due to the large size (150 kb) of the ataxia-telangiectasia mutated (ATM) gene
      and the existence of over 400 mutations, identifying mutations in patients with
      ataxia-telangiectasia (A-T) is labor intensive. We compared the SNP and STR
      haplotypes of A-T patients from varying ethnicities who were carrying common ATM
      mutations. We used SSCP to determine SNP haplotypes. To our surprise, all of the
      most common ATM mutations in our large multiethnic cohort were associated with
      specific SNP haplotypes, whereas the STR haplotypes varied, suggesting that ATM
      mutations predated STR haplotypes but not SNP haplotypes. We conclude that these
      frequently observed ATM mutations are not hot spots, but have occurred only once
      and spread with time to different ethnic populations. More generally, a
      combination of SNP and STR haplotyping could be used as a screening strategy for
      identifying mutations in other large genes by first determining the ancestral SNP
      and STR haplotypes in order to identify specific founder mutations. We estimate
      this approach will identify approximately 30% of mutations in A-T patients across
      all ethnic groups.

PMID- 12497635
TI  - Mutation scanning by ion-pair reversed-phase high-performance liquid
      chromatography-electrospray ionization mass spectrometry (ICEMS).
AB  - Partially denaturing high-performance liquid chromatography has emerged as the
      most sensitive physical mutation scanning method. However, there are a few
      reports of mutations missed or only detectable at unique temperatures. The
      combined use of ion-pair reversed-phase high-performance liquid chromatography
      under completely denaturing conditions and electrospray ionization quadrupole ion
      trap mass spectrometry (ICEMS) obviates the need for selecting appropriate
      temperatures for resolving heteroduplices and allows the discrimination of
      different alleles even when they co-elute due to distinct mass differences
      between nucleobases. This was demonstrated for the detection of four mutations
      (259G>A, 286A>G, 300T>G, and 331+1G>A) in exon 5 and intron 5 of BRCA1,
      respectively. Current mass resolution of quadrupole ion trap mass spectrometers
      limits the identification of single A>T or T>A transversions with a mass
      difference of 9 Da to fragments <80 base pairs (bp). The presence of all other
      mutations can be detected in fragments up to approximately 105 bp. The approach
      may prove particularly useful in the mutational scanning of AT- or GC-rich
      sequences that are recalcitrant to most other methods.

PMID- 12497636
TI  - MEFV sequence variants and amyloidosis: still an enigmatic question.

PMID- 12497637
TI  - Evaluation of Cx26/GJB2 in German hearing impaired persons: mutation spectrum and
      detection of disequilibrium between M34T (c.101T>C) and -493del10.
AB  - Mutations in the connexin 26 gene (GJB2) are responsible for the major part of
      nonsyndromic autosomal recessive or apparently sporadic prelingual deafness in
      Caucasians (DFNB1). We screened 228 German hearing-impaired persons for mutations
      in the GJB2 gene by sequence analysis. Homozygous or compound heterozygous GJB2
      mutations were detected in 38/228 (16.7%) of hearing impaired persons. The most
      frequently occurring mutation was the c.35delG mutation, which was found in 71.1%
      of the mutated alleles. The next frequent mutation detected in the group of
      hearing impaired persons was the c.101T>C mutation (9/76 alleles; 11.8%). One new
      mutation, c.567delA, was observed. We further studied the presence of a 10bp
      deletion in the 5' UTR of the GJB2 gene (c.-493del10) which was assumed to occur
      together with the c.101T>C mutation. Ten out of thirteen patients (76.9%) were
      found to be carriers of both the c.101T>C mutation and the 10bp variant and in
      7/14 alleles a linkage disequilibrium between c.101T>C and the 10bp deletion was
      proven. In 4/14 alleles the linkage was ruled out and for the remaining 3 cases
      the phase determination was not possible. Seventy one controls were screened for
      the prevalence of Cx26 mutations and for the c.-493del10 variant. Heterozygosity
      frequency in the control group was for c.35delG 4.2%, for c.101T>C 1.4% and for
      c.-493del10 it was 5.6%.

PMID- 12497638
TI  - BRCA1 germline mutations in Indian familial breast cancer.
AB  - Germline mutation analysis of BRCA1 gene has demonstrated significant allelic
      heterogeneity. These differences represent historical influences of migration,
      population structure and geographic or cultural isolation. To date, there have
      been no reports of Indian families with mutations in BRCA1. We have screened for
      mutations in selected coding exons of BRCA1 and their flanking intron regions in
      three breast or breast and ovarian cancer families with family history of three
      or more cases of breast cancer under age 45 and/or ovarian cancer at any age. We
      have also analyzed 10 female patients with sporadic breast cancer regardless of
      age and family history, as well as 50 unrelated normal individuals as controls.
      Thus a total of 90 samples were analyzed for BRCA1 mutations using polymerase
      chain reaction-mediated site directed mutagenesis (PSM) and single stranded
      conformation polymorphism (SSCP) analysis for various selected exons followed by
      sequencing of variant bands. Eight point mutations were identified. Two
      deleterious pathogenic, protein truncating non-sense mutations were detected in
      exon 11 (E1250X) and exon 20 (E1754X) and six novel and unique amino acid
      substitutions (F1734S, D1739Y, V1741G, Q1747H, P1749A, R1753K). One complex
      missense mutation of exon 20 [V1741G; P1749A] was seen in two out of three
      families and another complex combination of missense and non-sense mutations of
      the same exon [V1741G; E1754X] was observed in only one family. These complex
      mutations exist only in breast cancer families but not in control populations of
      women. Three splice site variants (IVS20+3A>C, IVS20+4A>T, IVS20+5A>T) and two
      intronic variants (IVS20+21_22insG, IVS20+21T>G) were also detected. In the group
      of 10 sporadic female patients no mutations were found.

PMID- 12497639
TI  - Mutations spectrum of GNE in hereditary inclusion body myopathy sparing the
      quadriceps.
AB  - Hereditary Inclusion Body Myopathy (HIBM) is a unique group of neuromuscular
      disorders characterized by adult onset and a typical muscle pathology. We have
      recently identified the gene encoding for a bifunctional enzyme, UDP-N
      acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE), as the mutated
      gene in the prototype form of the disease presenting quadriceps sparing,
      particularly common in Middle Eastern Jews. Interestingly, we have identified the
      homozygous M712T Middle Eastern Jewish mutation also in two unrelated Middle
      Eastern Moslem families. We have also evaluated the involvement of GNE in several
      families from worldwide non-Jewish ethnic origins presenting symptoms similar to
      the Middle Eastern HIBM prototype. A total of 14 GNE mutations were identified
      (one nonsense and 13 missense), of which six are novel: an homozygous missense
      mutation in a consanguineous family from Italy and in a non consanguineous family
      from USA, and distinct compound heterozygotes in families from Germany, Italy,
      Ireland, Bahamas, USA and East India. This study brings to 17 the number of
      reported GNE mutations in quadriceps sparing myopathy, occurring either in the
      epimerase or the kinase domain of the enzyme. The mechanism leading to this
      unique phenotype still remains to be elucidated.

PMID- 12497640
TI  - Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille
      syndrome.
AB  - Alagille syndrome (AGS) is an autosomal dominant disorder characterized by five
      major symptoms: cholestasis, vertebral deformity, heart malformations, ocular
      defects and peculiar facial appearance. The previously described Jagged1 (JAG1)
      gene on chromosome 20p12 has been identified as being responsible for AGS. JAG1
      encodes a transmembrane protein acting as ligand for the evolutionarily conserved
      Notch signaling pathway. Here we report 36 novel mutations in the JAG1 gene. We
      identified 12 novel deletions, 4 insertions, 8 missense, 7 nonsense and 5 splice
      site mutations. All mutations map to the sequence encoding the extracellular part
      of the Jagged1 protein. The mutations spread over the entire gene with slightly
      increased rates in exons 2 to 6 and exon 23 and 24. Eight novel missense
      mutations map to the Delta-Serrate-Lag2 (DSL) domain and adjacent sequences which
      are important for ligand-receptor interaction. Inheritance was determined in 27
      families. Sixteen mutations (55%) were de novo and eleven mutations (45%) were
      transmitted. Altogether 226 different JAG1 mutations have been described in
      association with AGS, including our novel 36 mutations. AGS variants are spread
      over the entire gene with only a few mutations in exon 26. A relatively high
      number of mutations are clustered in exons 2 to 6. This sequence region shows
      high interspecies conservation and encodes the Notch receptor-binding region (DSL
      domain).

PMID- 12497641
TI  - Novel mutations in the Charcot-Marie-Tooth disease genes PMP22, MPZ, and GJB1.
AB  - Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous
      disorder of the peripheral nervous system. CMT type 1 is most frequently caused
      by a 1.4 Mb tandem duplication in chromosome 17p11.2 comprising the peripheral
      myelin protein 22 (PMP22) gene. Furthermore sequence variations of PMP22, myelin
      protein zero (MPZ) and the gap junction protein b 1 gene (GJB1 or Connexin 32)
      may cause a variety of distinct CMT phenotypes. In this study we screened DNA
      from 42 unrelated patients for mutations in the PMP22, MPZ and GJB1 genes. Four
      novel mutations were identified. A Val65Phe amino acid exchange in PMP22 causes
      CMT type 1 associated with deafness, in GJB1 Tyr7_Thr8delinsSer, Pro172Ala and
      Ser138Asn are causes of CMTX neuropathies".

PMID- 12497642
TI  - Glucose-6-phosphate dehydrogenase (G6PD) variants in Malaysian Malays.
AB  - We performed DNA analysis using cord blood samples on 86 male Malay neonates
      diagnosed as G6PD deficiency in the National University of Malaysia Hospital by a
      combination of rapid PCR-based techniques, single-stranded conformation
      polymorphism analysis (SSCP) and DNA sequencing. We found 37.2% were 871G>A (G6PD
      Viangchan), 26.7% were nt 563 C>T (G6PD Mediterranean) and 15.1% were 487G>A
      (G6PD Mahidol) followed by 4.7% 1376G>T (G6PD Canton), 3.5% 383T>C (G6PD Vanua
      Lava), 3.5% 592C>T (G6PD Coimbra), 2.3% 1388G>A (G6PD Kaiping), 2.3% 1360C>T
      (G6PD Union), 2.3% 1003G>A (G6PD Chatham), 1.2% 131C>G (G6PD Orissa) and 1.2%
      1361G>A (G6PD Andalus). Seventy-one (82.6%) of the 86 G6PD-deficient neonates had
      neonatal jaundice. Fifty seven (80%) of the 71 neonates with jaundice required
      phototherapy with only one neonate progressing to severe hyperbilirubinemia
      (serum bilirubin >340 micromol/l) requiring exchange transfusion. There was no
      significant difference in the incidence of neonatal jaundice, mean serum
      bilirubin level, mean age for peak serum bilirubin, percentage of babies
      requiring phototherapy and mean number of days of phototherapy between the three
      common variants. In conclusion, the molecular defects of Malay G6PD deficiency is
      heterogeneous and G6PD Viangchan, Mahidol and Mediterranean account for at least
      80% of the cases. Our findings support the observation that G6PD Viangchan and
      Mahidol are common Southeast Asian variants. Their presence in the Malays
      suggests a common ancestral origin with the Cambodians, Laotians and Thais. Our
      findings together with other preliminary data on the presence of the
      Mediterranean variant in this region provide evidence of strong Arab influence in
      the Malay Archipelago.

PMID- 12497643
TI  - Splice mutations in the p53 gene: case report and review of the literature.
AB  - Splice mutations in the p53 gene (TP53) are described as rare events that occur
      at a frequency of less than 1%. Using a functional assay based on the
      transcriptional activity of p53 and using RNA as starting material, we describe
      here a p53 splice mutation that could not be detected by genomic sequencing. This
      lack of detection is due to a deletion of the region complementary to primers
      commonly used for amplification. Reviewing the literature, we show that p53
      splice mutations have been certainly underestimated and that careful strategy
      should be used for a complete mutational analysis of the p53 gene. Furthermore,
      some p53 gene mutations described as "neutral" due to the absence of any amino
      acid change are truly deleterious, as they affect gene splicing.

PMID- 12497645
TI  - Psychometric properties and three proposed subscales of a self-report version of
      the Liebowitz Social Anxiety Scale translated into Hebrew.
AB  - We investigated the overall test-retest reliability and other psychometric
      properties of a self-report version of the Liebowitz Social Anxiety Scale (LSAS)
      translated into Hebrew. We also evaluated the utility of three new subscales that
      were identified by nonparametric analysis (multidimensional scaling; MDS). Two
      hundred and seven patients who sought treatment for social anxiety or panic
      disorder were evaluated. All patients completed the self-administered version of
      the LSAS. A subsample completed the LSAS a second time prior to the beginning of
      treatment. The results indicate that the self-report format of the LSAS
      translated into Hebrew demonstrates high test-retest reliability, internal
      consistency, and discriminant validity. Additionally, some evidence for
      convergent and divergent validity was noted, and treatment sensitivity was high.
      MDS analysis followed by the investigation of common underlying facets for items
      related in two-dimensional space identified three subgroups: 1) the Group
      Performance/Interaction ("Group") subscale that consists of group performance and
      group interaction items; 2) the Dyadic Interaction ("Dyadic") subscale that
      consists of Dyadic interaction items; and 3) the Public Activities ("Public")
      subscale that consists of individual activities carried out in public. The three
      new subscales identified by MDS appear to provide clinically relevant information
      that relates to both demographic and treatment outcome variables and warrant
      further study.

PMID- 12497646
TI  - Panic disorder patients at the time of air strikes.
AB  - We assessed the impact of real danger on several aspects of the panic disorder
      (PD) patients' psychopathology and level of disability. At the time of the NATO
      air strikes on Belgrade, 84 PD patients who were in partial or complete remission
      were administered the Panic and Agoraphobia Scale (PAS). All had been treated
      previously, and the majority (58.3%) were taking antipanic medications. The PAS,
      which was used as part of the regular follow-up assessment battery for PD
      patients, measures the overall severity of PD and the severity of key aspects and
      components of PD. Compared to the PAS assessments made before the onset of air
      strikes, the PAS assessments made at the time of air strikes showed significant
      differences in terms of decreased overall severity of PD, fewer health concerns,
      decrease in the level of disability, and greater intensity and frequency of
      anticipatory anxiety. Differences on the measures of panic attacks and
      agoraphobic avoidance were negligible. These results suggest that there is no
      relationship between panic attacks and real danger and lend support to the notion
      that panic attacks and fear induced by real danger are different phenomena.
      Contrary to the expectations of many PD patients, the presence of real danger
      does not seem to be associated with deterioration in their functioning, and PD
      patients can be reassured that they are not likely to cope worse under conditions
      of danger.

PMID- 12497647
TI  - Racial differences in psychotic symptoms among combat veterans with PTSD.
AB  - We tested the hypothesis that race may influence clinical presentation and
      symptomatology in combat veterans with posttraumatic stress disorder (PTSD).
      African-American and Caucasian veterans were administered the Psychotic Screen
      Module of the Structured Clinical Interview for DSM, Minnesota Multiphasic
      Personality Inventory-2 (MMPI-2), and other psychometric measures at a Veterans
      Affairs outpatient PTSD clinic. Subjects were consecutive referrals who were not
      matched for level of combat trauma or preexisting trauma; however, there were no
      group differences in other relevant demographic or diagnostic variables.
      Significant racial differences, with modest effect sizes, were found on clinician
      ratings of psychotic symptoms, MMPI-2 scale 6 ("paranoia"), and a measure of
      dissociation. No significant differences were found for the MMPI-2 scale 8
      ("schizophrenia"), or on measures that might suggest comorbid depression or
      anxiety. African-Americans with PTSD endorsed more items suggesting positive
      symptoms of psychosis, without higher rates of primary psychosis, depression, or
      anxiety than Caucasians.

PMID- 12497648
TI  - Generalized anxiety disorder: prevalence, burden, and cost to society.
AB  - Generalized anxiety disorder (GAD) is a prevalent and disabling disorder
      characterized by persistent worrying, anxiety symptoms, and tension. It is the
      most frequent anxiety disorder in primary care, being present in 22% of primary
      care patients who complain of anxiety problems. The high prevalence rate of GAD
      in primary care (8%) compared to that reported in the general population (12
      month prevalence 1.9-5.1%) suggests that GAD patients are high users of primary
      care resources. GAD affects women more frequently than men and prevalence rates
      are high in midlife (prevalence in females over age 35: 10%) and older subjects
      but relatively low in adolescents. The natural course of GAD can be characterized
      as chronic with few complete remissions, a waxing and waning course of GAD
      symptoms, and the occurrence of substantial comorbidity particularly with
      depression. Patients with GAD demonstrate a considerable degree of impairment and
      disability, even in its pure form, uncomplicated by depression or other mental
      disorders. The degree of impairment is similar to that of cases with major
      depression. GAD comorbid with depression usually reveals considerably higher
      numbers of disability days in the past month than either condition in its pure
      form. As a result, GAD is associated with a significant economic burden owing to
      decreased work productivity and increased use of health care services,
      particularly primary health care. The appropriate use of psychological treatments
      and antidepressants may improve both anxiety and depression symptoms and may also
      play a role in preventing comorbid major depression in GAD thus reducing the
      burden on both the individual and society.

PMID- 12497649
TI  - The match-mismatch model and panic patients' accuracy in predicting naturally
      occurring panic attacks.
AB  - The match-mismatch model of panic states that panic disorder patients tend to
      overestimate the probability of panic prior to engaging in a fear-provoking
      situation. Furthermore, patients are expected to become more accurate in
      predicting panic over subsequent occasions of exposure. We tested the model with
      naturally occurring panic attacks. Patients rated the probability of a panic
      attack in the morning, and these ratings were compared to the actual occurrence
      of panic that day. Ratings were collected daily in a baseline period before
      treatment, during treatment, and again for 2 weeks after treatment. The results
      confirmed that panic disorder patients tend to overpredict the likelihood of
      panic. However, patients did not become more accurate in their predictions over
      time. In fact, overprediction bias increased because expectancy of panic remained
      stable, in spite of the decline of the frequency of panic from pre- to post-test.
      Thus, over a short course of therapy panic patients tend to persist in
      overestimating the chance that panic may occur. At baseline, expectancy of panic
      and the tendency to overpredict were not associated with other aspects of the
      symptomatology. Neither expectancy nor overprediction bias was predictive of
      treatment outcome. Finally, improvement in treatment was not associated with a
      decreased expectancy of panic.

PMID- 12497650
TI  - Etiological beliefs about chronic worry.

PMID- 12497651
TI  - The comparison of cytotoxic T-lymphocyte effects of dendritic cells stimulated by
      the folate binding protein peptide cultured with IL-15 and IL-2 in solid tumor.
AB  - The current modalities for treating cancer employ not only single but multiple
      approaches involving surgery, radiotherapy and chemotherapy. Unfortunately, the
      survival outcome is not promising even with these approaches. Alternative
      approaches for cancer therapy are now emerging. Immunotherapy is aiming at both
      increasing the power, and in redirecting the specificity of the patients' immune
      system to attack the tumor cells. Recently, many studies using tumor associated
      lymphocytes (TAL) isolated from malignant ascites cultured in a media containing
      interleukin-2 exhibit antitumor responses. IL-2 is a lymphokine produced by T
      cells. It facilitates activation, sustained growth and rescue from apoptosis.
      Lately, newly developed IL-15 has also exhibited antitumor activity similar to IL
      2. IL-15 is a newly described cytokine produced from monocytes-marcrophages and T
      cells. It has a different molecular structure but it functions like IL-2 by
      binding to the IL-2R beta and gammac chain. These antitumor responses are
      mediated by the cytotoxic T lymphocytes (CTL) that recognize the antigen in the
      context of the MHC molecules using the T cell receptors. CD8+-CTL recognize the
      peptide epitopes that are processed from the cellular proteins in the context of
      the MHC class I molecules. These peptides have a restricted length of 8-11 amino
      acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian
      and 20-50% in breast cancers. The FBP is the source of the antigenic peptides
      that are recognized by a number of these CTL-TAL, and is antigenic to both
      ovarian and breast cancer in vivo. To define the antitumor response of IL-15 and
      its' FBP immunogenicity, a peptide defining epitope E39 and E75 were presented by
      the PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14
      method to ovarian and breast CTL-TAL. Stimulating both ovarian and breast CTL-
      TAL by E39 or E75 pulsed DC (DC-E39, DC-E75), in the presence of IL-15 and IL-2
      can rapidly enhance or induce the E39 or E75 specific CTL activity. The antitumor
      activities were measured by a chromium release assay for the tumor specific lysis
      activity using the ovarian and breast cancer cell lines. The tumor specific lysis
      activity for the ovarian TALs for IL-15 vs IL-2 were 28.6 +/- 3.9% and 30.3 +/-
      3.2%, respectively and in the breast TALs, they were 14.8 +/- 3.1% vs 13.5 +/-
      2.9%, respectively. Using autologous tumor cells, a slightly higher tumor
      specific lysis activity was obtained for the ovarian TALs cultured in IL-15
      compared to IL-2 (72.0 +/- 8.2% vs 68.5 +/- 3.6%). However, for the breast TALs,
      they were 39.5 +/- 4.2% vs 41.5 +/- 3.3%, respectively. IL-15 is a newly
      developed cytokine that shows promising antitumor activity similar to IL-2.
      However, it requires lower dosage and is less toxic. Therefore, IL-15 might be a
      potential anticancer immunotherapeutic agent.

PMID- 12497652
TI  - Expression of E-cadherin and alpha-, beta-, gamma-catenin proteins in endometrial
      carcinoma.
AB  - Loss of the cell adhesion molecule E-cadherin is suggested to promote tumor
      invasion and distant metastasis in tumor development. Recently, it has been
      proposed that E-cadherin function requires its linkage to the cytoskeleton
      through catenins. We evaluated the expression of E-cadherin and alpha-, beta-,
      gamma-catenins in tissues of human endometrial carcinoma, analyzed the patterns
      of cell adhesion molecules' expression in endometrial carcinoma and investigated
      the relationship between the statuses of cell adhesion molecules and various
      clinicopathological factors. This study investigated the immunohistochemical
      expression of E-cadherin and alpha-, beta-, gamma-catenins in 33 paraffin
      embedded formalin fixed tissues of endometrial carcinomas. Aberrant E-cadherin,
      and alpha-, beta-, gamma-catenin expression was observed in 33.3 (11 of 33), 27.3
      (9 of 33), 18.2 (6 of 33), and 51.5 (17 of 33) % of the specimens, respectively.
      Statistically significant correlation was found between aberrant expression of E
      cadherin and lymph node metastasis and cell types other than endometrioid
      adenocarcinoma. Aberrant pattern of gamma-catenin expression was also correlated
      with deep myometrial invasion. However, alpha-, and beta-catenin expression was
      not correlated with any clinicopathological parameters. Using the Kaplan-Meier
      method and log-rank comparison test, abnormal expression of E-cadherin was
      correlated closely with poor survival (p < 0.05), but cases with loss of both E
      cadherin and catenin expression predicted even poorer survival than cases with
      only one or no aberrant expression in E-cadherin and catenins. We revealed
      aberrant expression of these cell adhesion molecules among patients with
      endometrial carcinoma. Aberrant expression of E-cadherin was correlated with
      lymph node metastasis and cell types other than endometrioid adenocarcinoma,
      while aberrant expression of gamma-catenin was related with deep myometrial
      invasion. The expression of E-cadherin might be a possible prognostic factor for
      endometrial cancer while the expression of catenins may help predict patient's
      survival.

PMID- 12497653
TI  - GSTP1 polymorphism, cigarette smoking and cervical cancer risk in Korean women.
AB  - Previous studies have suggested that glutathione S-transferase (GST) genotypes
      may play a role in determining susceptibility to cervical cancer, though the data
      have often been conflicting. The objective of this study was to examine the
      effect of GSTP1 polymorphism on cervical carcinogenesis. The studied subjects,
      patients who were pathologically diagnosed with invasive cervical cancer yielding
      positive results for human papillomavirus (HPV) (n=342), were compared to
      healthy, normal, female controls (n=707). DNA from peripheral blood samples from
      studied subjects whose GSTP1 specific sequences had been determined by PCR with
      allele-specific primers were reviewed in comparison with the normal controls. The
      genetic susceptibility of GSTP1 (11q 13.1) in cervical carcinogenesis was
      determined by examining the effect of gene and environmental factors by the
      different histopathologic types of invasive cervical cancers. In assessing
      polymorphism GSTP1, the percentages of individuals homozygous for the A allele,
      homozygous for the G allele, and heterozygous for the two alleles were 66.8%,
      3.9%, and 29.3%, respectively, in the control group, and 64.3%, 4.1%, and 31.6%,
      respectively, among in women with cervical cancer. Compared with GSTP1 G allele
      positive (GA or G/G), the odds ratio (OR) (95% confidence interval) for GSTP1 A/A
      was 1.0 (0.7 - 1.4) for invasive cervical cancer. However, the risk increased
      with GSTP1 A/A among ever smokers (3.9, 1.7 - 8.9, p-value=0.0012) compared with
      GSTP1 G allele positive among nonsmokers. In particular, this risk was higher
      among women with squamous cell carcinoma (4.7, 2.0 - 10.8, p=0.0003).
      Polymorphism of GSTP1 among smoking women was associated with a higher risk of
      developing cervical cancer.

PMID- 12497654
TI  - Screening the high risk patient for gynaecological cancer.
AB  - It is often difficult to conclude that improvements in survival with time are due
      to a screening programme alone. Although a reduction in the death rate from a
      given cancer may reflect the benefits of early detection or improved treatment,
      the benefits may also result from lead time bias and over-diagnosis, the former
      resulting in longer survival of screen-identified cancers because the time before
      the cancer would have been clinically diagnosed is included in calculations.
      Furthermore, recent reviews on randomised clinical trials of cancer screening
      have provided strong evidence that misclassifications in causes of death have
      been a major problem, leading to an over-estimation of the effectiveness (or
      alternatively an under-estimation of potential harm) of screening.

PMID- 12497655
TI  - Alteration of cell cycle in cervical tumor associated with human papillomavirus:
      cyclin-dependent kinase inhibitors.
AB  - The ability of viral oncoproteins to subvert cell cycle checkpoints may
      constitute a mechanism by which viral oncoproteins induce genetic instability.
      HPV 16 E6 and E7 disrupt cell cycle checkpoints, particularly affecting nearly
      all cyclin-dependent kinase inhibitors linked to the G1- and G2- checkpoints, in
      each case by means of a different mechanism. HPV 16 E7 shows homology with the
      pRb binding sites of cyclin D1, which consequently releases E2F. In addition, E7
      directly binds to p21, and releases PCNA and other S-phase promoting genes. In
      turn, released E2F activates cyclin E, and cyclin E accelerates p27 proteolysis
      as a function of the antagonistic reaction of its own inhibitor. The induction of
      p16 expression is assumed to be indirectly associated with E7, which is
      upregulated only after prolonged inactivation of Rb. HPV 16 E6 decreased the
      fidelity of multiple checkpoints controlling both entry into and exit from
      mitosis, with the mechanism of p53 inactivation. In addition, HPV 16 E6 increased
      the sensitivity to chemically induced S-phase premature mitosis and decreased
      mitotic spindle assembly checkpoint function. Alongside the impressive advances
      made in the understanding of the molecular mechanisms, which HPV disrupts, the
      validity of these conclusions should be evaluated in the diagnostic and
      prognostic fields.

PMID- 12497656
TI  - Advances in cervical cancer management from North American cooperative group
      clinical trials.
AB  - Despite effective screening methods for detecting pre- malignant diseases of the
      cervix, cervical cancer remains a leading cause of cancer mortality in women
      globally. There has been a dramatic decline in the age adjusted death rate from
      cervical cancer in the United States, where cervical cancer has declined from the
      leading cause of cancer mortality in women prior to 1940 to a point where it is a
      relatively uncommon cause of cancer mortality today. Despite these advances in
      screening and early detection reported in the United States, intraepithelial
      disease detection rates in many non-industrialized countries remain low because
      screening programs are generally lacking. As a result most cancers detected in
      many underdeveloped areas of the world are advanced at diagnosis. Furthermore, in
      such countries there may be inadequacies in physicians trained in the most
      effective means of treating cervical cancer, technical support required for the
      effective delivery of radiation therapy or the administration of chemotherapy,
      and modern equipment required for optimal treatment with radiation therapy. Thus
      cure rates for women with cervical cancers in many areas of the world remain low.

PMID- 12497658
TI  - Concurrent chemoradiotherapy in cervical cancer (a new paradigm in cervical
      cancer treatment).
AB  - During the last century, the mainstay for the treatment of uterine cervix cancer
      has been via two main primary treatment modalities, these being radical surgery
      (radical hysterectomy and regional lymph nodes dissection) and radiotherapy.
      Generally, radical surgery is restricted to stages I and IIa of FIGO (the
      International Federation of Gynecology and Obstetrics) Classification, while
      radiotherapy may be applied to all stages of cervical cancer. In 1999 the
      National Cancer Institute Clinical Announcement established concurrent
      chemoradiotherapy as a new primary treatment modality, which is the focus of this
      review.

PMID- 12497657
TI  - Fractionated high-dose-rate brachytherapy in the management of uterine cervical
      cancer.
AB  - It is well known that intracavitary radiotherapy (ICR), either alone or in
      combination with external-beam radiotherapy (EBRT) is an essential component of
      the radiation treatment of uterine cervical cancer. Although low-dose-rate (LDR)
      brachytherapy has been successfully applied to the management of such patients,
      several radiation oncologists have experience of using high-dose-rate (HDR)
      brachytherapy with promising clinical results over the past 4 decades. However,
      there has been a considerable reluctance by radiation oncologists and
      gynecologists in North America to employ the HDR remote afterloading technique
      instead of the more firmly established LDR treatment modality. In contrast, the
      HDR-ICR system is rapidly gaining acceptance in Korea since the introduction of
      the Ralstron, remotely controlled afterloading system using HDR Co-60 sources, at
      the Yonsei Cancer Center in 1979. According to brachytherapy statistics reported
      by the Korean Society of Therapeutic Radiology and Oncology, in 1997,
      brachytherapy was performed upon 1,758 Korean patients with uterine cervical
      cancer, of whom approximately 83% received HDR brachytherapy. In this review, we
      present our experiences of HDR-ICR for the treatment of uterine cervical cancer.
      In addition, we discuss the controversial points, which are raised by those
      considering the use of HDR-ICR for uterine cervical cancer; these issues include
      physical and radiobiological considerations, and the prospect of future technical
      improvements.

PMID- 12497659
TI  - Surgical management of recurrent cervical cancer.
AB  - The majority of patients with recurrent cervical cancer are incurable and
      treatment is based on the type of primary therapy delivered. Only a very small
      percentage of the patients with recurrent cervical cancer following primary
      radiotherapy will have central pelvic recurrences that are amenable to surgical
      resection and curable by pelvic exenteration. These procedures should be
      undertaken only after the completion of exhaustive attempts to exclude
      extrapelvic disease.

PMID- 12497660
TI  - The application of human papillomavirus testing to cervical cancer screening.
AB  - Although cytologic screening has considerably reduced the incidence of cervical
      cancer, there are some problems which remain to be solved, such as the low
      sensitivity of this procedure. HPV testing is fundamentally different from
      conventional cytologic testing, because it evaluates the HPV infection itself,
      the most important causative factor for cervical cancer. In this study, the roles
      and clinical applications of HPV testing in cervical cancer screening are
      examined from 3 standpoints: in primary screening, in the management of women
      with low-grade cytologic abnormalities, and in the follow-up after treatment of
      pre-invasive or early invasive lesions.

PMID- 12497661
TI  - Clinicopathologic and biological parameters predicting the prognosis in
      endometrial cancer.
AB  - Endometrial carcinoma is the most common malignancy of the female genital tract
      in United States or Europe, but in Korea, its incidence is comparatively low than
      that of cervical cancer of uterine cervix. Recently the prolonged life
      expectancy, postmenopausal use of hormone replacement therapy, and the
      availability of easily applied diagnostic techniques have led to increasing
      incidence of endometrial cancer. Although during the past several decades, the
      histopathology, spread patterns, and prognostic factors of endometrial cancers
      have been better defined, the clinicopathologic and biologic prognostic
      parameters should be further evaluated for the better treatment results in
      endometrial cancer.

PMID- 12497662
TI  - Pitfall in chemotherapy for ovarian cancer.
AB  - Concerning the biological properties of recurrent ovarian cancer, other than drug
      resistance, we revealed that the expressions of mutant p53 and CD44v6 genes were
      significantly greater in recurrent ovarian cancer than in those of its primary
      counterpart. These findings suggest that chemotherapeutic agents may modify some
      biological characteristics of cancer by altering gene expressions. The biological
      behavior concerning the metastatic potential of a recurrent disease must be
      elucidated in order to develop an optional treatment regimen against recurrent
      tumors. Therefore, we established in-vivo cisplatin-resistant cell lines by
      repeated administration, in order to find a more suitable model for reflecting
      the biological aggressiveness of clinically recurrent ovarian cancer following
      chemotherapy. Chemotherapeutic agents have given a substantial advantage to
      cancer patients. It must be borne in mind that the cancer cells surviving
      following chemotherapy possibly present different biological properties from
      primary cancer cells, and that these properties might be developed by the
      chemotherapeutic agents.

PMID- 12497663
TI  - Lymph node metastasis in a gynecologic malignancy.
AB  - A radical hysterectomy was performed on patients with stage IA2 to IIB cervical
      cancer. For these patients, many histopathological parameters have been reported
      to be prognostic factors of cervical cancer, such as a pelvic lymph node (PLN)
      metastasis, the histological subtype, the tumor diameter, the depth of the
      stromal invasion, a lymph-vascular space invasion (LVSI), a parametrial invasion,
      a corpus invasion and a vaginal invasion. Ovarian cancer is normally treated with
      cytoreductive surgery followed by chemotherapy. Although physicians have paid a
      great deal of attention to intraperitoneal disease, a substantial number of
      ovarian cancers have reported to involve the retroperitoneal lymph nodes.
      Therefore, a lymph node metastasis has been introduced into FIGO staging.
      However, the prognostic significance of a lymph node metastasis is controversial.
      In order to determine the possibility of individualizing a pelvic lymph node
      (PLN) dissection in patients with endometrial cancer, the relationship between
      PLN metastasis and the various prognostic factors was investigated. In this
      paper, various prognostic variables including a lymph node metastasis were
      analyzed in cervical cancer, endometrial cancer, and ovarian cancer.

PMID- 12497664
TI  - Hyponatremia in a cold weather ultraendurance race.
AB  - We assessed the incidence and etiology of hyponatremia in the 100-mile (161 km)
      Iditasport ultramarathon. Subjects (8 cyclists, 8 runners) were weighed and serum
      sodium was measured pre- and post-race. Race diets were analyzed to determine
      fluid and sodium consumption. Subjects were split by post-race serum sodium
      concentration into hyponatremic and normonatremic groups for statistical
      analyses. Seven of 16 subjects (44%) were hyponatremic. The hyponatremic group
      exhibited a significant decrease in serum sodium concentration (137.0 to 132.9
      mmol/L), and the normonatremic group experienced a significant decrease in weight
      (82.1 to 80.2 kg) pre- to post-race. The hyponatremic group drank more fluid per
      hour (0.5 versus 0.4 L/h) and consumed less sodium per hour (235 versus 298 mg/h)
      compared to the normonatremic group. In conclusion, hyponatremia is common in an
      ultraendurance race held in the extreme cold, and may be caused by excessive
      fluid consumption and/or inadequate sodium intake.

PMID- 12497665
TI  - Anal cancer in Alaska; a retrospective study of incidence, treatment, and
      outcomes.
AB  - Anal cancer is a rare tumor usually of squamous histology that is managed most
      often with concurrent chemotherapy and radiation therapy. Surgery is commonly
      reserved for those who fail primary treatment. We conducted a retrospective
      analysis of the medical records of patients with anal cancer seen in two
      radiation therapy centers in Alaska from the period of 1996 to mid-2001. Records
      were reviewed for diagnosis, sex, age, staging, treatment and outcomes. Twenty
      four patients were identified with squamous cell carcinoma of the anus. Average
      age at diagnosis was 53. Tumor size was predominantly 2-5 centimeters. Four
      patients had nodal involvement and three had distant metastasis. Twenty patients
      received radiation. Nineteen received flourouracil and either cisplatin or
      mitomycin. Three patients underwent abdominoperineal resections. Ten were found
      to have no evidence of disease at an average of twenty-two months. These results
      are consistent with findings of larger studies elsewhere.

PMID- 12497666
TI  - Neurilemmoma: an unusual benign tumor of the cervix.
AB  - BACKGROUND: A Neurilemmoma (also called Schwannoma) is a benign, slowly growing
      neoplasm of the Schwann cells which may occur in association with any nerve. Its
      finding in the cervix of the uterus is extremely rare. CASE: At a routine annual
      exam, a 47-year-old woman was found to have a tumor on the posterior lip of the
      cervix. The patient was completely asymptomatic. The tumor was excised using a
      large electrical loop (LEEP) and found to be a benign Neurilemmoma. Subsequently
      a CT scan of the pelvis did not reveal any other abnormalities and no further
      treatment was contemplated. CONCLUSION: A benign neurilemmoma can present on the
      cervix as a vascular appearing tumor. This is a most unusual location for this
      tumor which arises from the Schwann cell of a nerve sheet.

PMID- 12497667
TI  - Traditional medical cures along the Yukon.

PMID- 12497668
TI  - Community facilities v.s. volume institutions.

PMID- 12497669
TI  - Oral contraception update: focus on a new progestin. November 2002.

PMID- 12497670
TI  - Oral contraception: trends over time.
AB  - Since their introduction in 1960, oral contraceptives have undergone an evolution
      in content and dosage. The doses of the steroid components of combination oral
      contraceptives have been dramatically decreased since the first formulations.
      Ethinyl estradiol is now used as the estrogenic component of most combination
      oral contraceptives. The majority of progestins currently used in combination
      oral contraceptives are derivatives of 19-nortestosterone. However, drospirenone,
      which is combined with ethinyl estradiol in a new combination oral contraceptive,
      is a novel progestin that is derived from 17 alpha-spirolactone and is an
      analogue of spironolactone. The extremely low failure rate with ideal use of
      combination oral contraceptives is seldom duplicated in actual usage. Women often
      discontinue combination oral contraceptives within the first 2 months due to side
      effects that would likely have decreased over time. Although there are some areas
      of increased health risk with combination oral contraceptives, the benefits far
      outweigh the potential risks. In addition to providing effective contraception,
      combination oral contraceptives are sometimes used for their many
      noncontraceptive health benefits--e.g., treatment of menstrual irregularities and
      management of premenstrual symptoms. The most practical solution to the problem
      of poor compliance appears to lie in providing adequate education and counseling
      to women using combination oral contraceptives so that they know how to use them
      properly and what side effects they might expect. Patients also need to be given
      the facts about potential increases in the risk of certain conditions to help
      correct any misperceptions.

PMID- 12497671
TI  - Evolution of progestins. Focus on the novel progestin drospirenone.
AB  - Combination oral contraceptives have changed considerably since they were
      introduced, in 1960. Although ethinyl estradiol has been the primary estrogen in
      combination oral contraceptives for years, a number of progestogenic agents have
      been developed. All of the progestins currently used in combination oral
      contraceptives are derived from 19-nortestosterone. The exception is a new
      progestin derived from 17 alpha-spirolactone--drospirenone. As compared with that
      of other progestins used in combination oral contraceptives, drospirenone
      pharmacology more closely resembles the pharmacology endogenous progesterone. Its
      antiandrogenic and antimineralocorticoid activities result in special benefits-
      e.g., improvement in androgen-related disorders (such as acne and hirsutism) and
      avoidance of estrogen-related fluid retention.

PMID- 12497672
TI  - Safety and efficacy of a new oral contraceptive containing drospirenone.
AB  - An oral contraceptive containing ethinyl estradiol and the unique progestin
      drospirenone provides a new contraceptive option. Ethinyl estradiol is the form
      of synthetic estrogen used in most oral contraceptives. Drospirenone differs from
      other synthetic progestins in that it is derived from 17 alpha-spirolactone and
      is an analogue of spironolactone. The oral contraceptive containing ethinyl
      estradiol and the unique progestin drospirenone has been shown to be highly
      efficacious and to provide safety equivalent to that of other oral contraceptive
      formulations.

PMID- 12497673
TI  - Quality of life issues. Potential role for an oral contraceptive containing
      ethinyl estradiol and drospirenone.
AB  - The new combined oral contraceptive containing ethinyl estradiol and drospirenone
      has the potential for improving a woman's quality of life. Drospirenone's
      antiandrogenic activity, for example, makes it effective in reducing acne and
      seborrhea. The majority of reproductive-age women suffer from some degree of
      premenstrual symptomatology. In some cases, these monthly symptoms are severe
      enough to negatively impact a woman's quality of life. Drospirenone's
      antimineralocorticoid activity aids in reducing some of the most bothersome
      symptoms associated with the premenstrual phase of the menstrual cycle.

PMID- 12497674
TI  - Ectopic pregnancy risk when contraception fails. A review.
AB  - OBJECTIVE: To alert clinicians to the risk of ectopic pregnancy when certain
      contraceptive methods fail by summarizing data from trials reviewed by the U.S.
      Food and Drug Administration (FDA). STUDY DESIGN: The review focuses on 7
      contraceptive drug products with an increased risk of ectopic pregnancy when the
      method fails. Data were extracted from reviews of clinical trials submitted to
      the FDA to support marketing applications and from the medical literature. Data
      on 6 other contraceptive drug products and published data for tubal ligations are
      used for comparison. This review does not include medroxyprogesterone acetate
      injections because the FDA reviews for this method did not include any pregnancy
      outcome information. RESULTS: The results are presented in a table and are
      compared to postmarketing surveillance reports and published literature, when
      available. The proportion of ectopic pregnancies among all pregnancies ranged
      from 1:2 to 1:21 for intrauterine devices, tubal ligations, progestin-only
      implants and progestin-only oral contraceptives. Although the confidence
      intervals for the proportions were large in trials with few pregnancies, both
      postmarketing surveillance reports and published literature support proportions
      calculated from clinical trial data. CONCLUSION: Pregnancies in women using
      progestin-only oral contraceptives, progestin-only implants, intrauterine devices
      and tubal ligations are more likely to be ectopic than pregnancies in the general
      population.

PMID- 12497675
TI  - Intraovarian stromal artery Doppler indices in predicting ovarian response.
AB  - OBJECTIVE: To determine the value of ovarian stromal artery Doppler indices in
      the prediction of ovarian response in in vitro fertilization-embryo transfer (IVF
      ET) cycles. STUDY DESIGN: Forty-five cases were involved in the study. Following
      controlled ovarian hyperstimulation and detection of at least three follicles >
      17 mm in diameter by transvaginal sonography in both ovaries, human chorionic
      gonadotropin was administered and follicle aspiration performed at the 34th-36th
      hour. The patients were separated into two groups according to the number of
      oocytes collected. Group I consisted of 8 (18%) patients who had three or fewer
      oocytes (low-responder cases); group II consisted of 37 (82%) patients who had 4
      or more oocytes (good-response cases). RESULTS: A significant negative
      correlation was found between both the stromal ovarian artery pulsatility index
      and the number of aspirated follicles (r = -.31, P = .04) and number of oocytes
      collected (r = -.32, P = .03). Although there was no significant correlation
      between the resistance index and number of aspirated follicles (r = .24, P =
      .12), a significant negative correlation was determined between the resistance
      index and number of oocytes collected (r = -.30, P = .04). Pulsatility and
      resistance indices were significantly different between the two groups (1.6 +/-
      0.5 and 1.2 +/- 0.5, P = .02, versus 0.7 +/- 0.08 and 0.6 +/- 0.08, P = .03,
      respectively). CONCLUSION: Blood flow in the vessels that supply blood to the
      follicles in the ovaries in the early follicular phase correlates significantly
      with ovarian response.

PMID- 12497676
TI  - Clinical predictors of cervical intraepithelial neoplasia 2 or greater in women
      with mildly abnormal Pap smears.
AB  - OBJECTIVE: To evaluate clinical predictors of cervical intraepithelial neoplasia
      (CIN) 2 or greater in women with mildly abnormal Pap smears. STUDY DESIGN: Using
      a computerized colposcopy database of 2,200 women, we identified 1,494 with
      atypical squamous cells of undetermined significance (ASCUS) or low grade
      squamous intraepithelial lesions (LSILs). Of the 1,494, 1,016 (68%) underwent
      biopsy and formed the cohort for this retrospective review. Clinical variables
      associated with CIN 2 or greater in a univariate analysis (P < .10) were included
      in a multivariate regression analysis. RESULTS: Of the 1,016 women biopsied, 195
      (19%) had CIN 2 or greater. In the initial analysis, age (< 35 years), race
      (Caucasian and African American), marital status (unmarried) and smoking status
      (current and former) were found to be significantly associated with more severe
      histologic disease. In the regression analysis, a history of smoking remained a
      statistically significant clinical predictor of CIN 2 or greater (odds ratio
      1.57, 95% confidence intervals 1.09-2.27). CONCLUSION: A significant predictor of
      CIN 2 or greater in a large cohort of women with mildly abnormal Pap smears was a
      history of current or former smoking.

PMID- 12497677
TI  - Clinical practice guidelines as educational tools for obstetrician-gynecologists.
AB  - OBJECTIVE: To examine the awareness of and attitudes toward clinical practice
      guidelines (CPGs) produced by the American College of Obstetricians and
      Gynecologists (ACOG) among its fellows and to identify factors that would enhance
      the perceived value of the CPGs. STUDY DESIGN: A questionnaire survey on clinical
      practice guidelines sent to 1,000 practicing fellows of ACOG. RESULTS: Four
      hundred sixty-two fellows (46.2%) responded. Virtually all (98%) were aware of
      ACOG CPGs; 61% stated that an ACOG CPG had changed their practice. Far fewer (6
      56%) were aware of CPGs from other organizations; 71.9% were aware of all eight
      ACOG CPGs that were added in 2000 (range, 83.3-90%). Important factors that would
      enhance the value of CPGs to the respondents were CPGs that were up to date, had
      demonstrated improved outcomes, were evidence based and were produced by ACOG.
      Barriers to use were CPGs without summaries, CPGs not specific to the fellows'
      settings, CPGs not taking patient cost into account and patient requests for
      different procedures. CONCLUSION: The widespread awareness by ACOG fellows of
      CPGs produced by ACOG demonstrates the potential importance of specialty
      societies in disseminating CPGs. The data suggest that important characteristics
      of CPGs are being up to date, being evidence based, containing a summary and
      providing patient education materials.

PMID- 12497678
TI  - Reappraisal of neonatal clavicular fracture. Relationship between infant size and
      risk factors.
AB  - OBJECTIVE: To examine the role of fetal size in neonatal clavicular fracture.
      STUDY DESIGN: A retrospective, case-control study was performed on infants
      diagnosed with neonatal clavicular fractures and born vaginally between July 1997
      and June 2000. For each index case, a control matched for gestational age (within
      one week) and birth weight (within 250 g) and delivered within the same 24-hour
      period was selected at random from the delivery suite registry. The maternal and
      intrapartum factors were compared and the results analyzed according to whether
      the infants were large for gestational age (LGA) or not. RESULTS: Among 9,540
      neonates delivered vaginally during this period, 151 (1.6%) had a fractured
      clavicle. Multivariate analysis indicated that the independent risk factors were
      shoulder dystocia and vacuum extraction. When analyzed according to fetal size,
      shoulder dystocia was significant only for LGA infants, while vacuum extraction
      was significant only for non-LGA infants. CONCLUSION: Independent risk factors
      for neonatal clavicular fracture are related to fetal size.

PMID- 12497679
TI  - Non-evidence-based use of Rho(D) immune globulin for threatened abortion by
      family practice and obstetric faculty physicians.
AB  - OBJECTIVE: To examine the practice patterns and differences between faculty
      members in obstetrics and gynecology (OB/G) and family practice (FP) residency
      programs in administering Rho(D) immune globulin (RhIG) for threatened abortion.
      STUDY DESIGN: A questionnaire was mailed to 50% (222) of all FP residencies and
      100% (267) of OB/G programs in the United States. The obstetric curriculum
      coordinator at each FP residency and the director of obstetrics or maternal-fetal
      medicine at each OB/G residency were asked to respond. A total of 156 (70%) FP
      questionnaires and 186 (70%) OB/G questionnaires were returned after two
      mailings. RESULTS: Seventy-six percent of FP faculty and 85% of OB/G faculty
      reported giving RhIG in threatened abortion. Physicians with advanced training
      were more likely to recommend giving RhIG. CONCLUSION: Most FP and OB/G residency
      faculty report using RhIG in threatened abortion. The practice has become part of
      the medical culture despite the lack of supporting evidence and should be
      revaluated in that light.

PMID- 12497680
TI  - CO2 laser surgery for vulvar intraepithelial neoplasia. Excisional, destructive
      and combined techniques.
AB  - OBJECTIVE: To evaluate CO2 laser excision, vaporization and combined techniques
      for treatment of vulvar intraepithelial neoplasia (VIN). STUDY DESIGN: Thirty
      nine cases of VIN 3, 15 cases of VIN 2 and 9 of VIN 1, for a total of 63 patients
      with histologically proven VIN, underwent laser excision or vaporization under
      colposcopic guidance, using local anesthesia, in an outpatient setting or after
      day-surgery admission. Clinical aspects, cervical intraepithelial neoplasia (CIN)
      and vaginal intraepithelial neoplasia (VaIN) association, types of CO2 laser
      treatment, follow-up, recurrences and second treatments were evaluated. RESULTS:
      Twenty-seven (41.3%) patients underwent laser vaporization, and 37 (58.7%) with
      VIN 3, underwent laser excision or the combined technique. Colposcopic and biopsy
      examinations of patients with VIN revealed three cases of CIN 3 and nine cases of
      VaIN 3; two patients had concomitant VIN 3, CIN 3 and VaIN 3. Local anesthesia,
      using 2% carbocaine, and outpatient or day-surgery treatments were possible in
      all cases. A small incidence of intraoperative complications (4.8%) and absence
      of postoperative complications were observed. A single session was curative in
      76.9% of patients treated with laser vaporization and in 78.4% of those treated
      with laser excision. Eleven cases of recurrent VIN and two cases of invasive
      vulvar carcinoma were observed during follow-up. A second laser procedure was
      carred out in all cases of relapsed VIN, with an overall cure rate of 96.8% after
      two treatments. Radical vulvectomy associated with inguinal-femoral
      lymphadenectomy was performed in the two cases of invasive carcinoma. CONCLUSION:
      CO2 laser surgery permits treatment of VIN in an outpatient or day-surgery
      setting under local anesthesia with excellent cosmetic and functional results.
      The treatment can also be adjusted to the patient's specific needs, with the
      possibility of calibrating the depth of the vaporized and removed tissues.
      Excisional treatment is the preferred method because it permits histologic
      evaluation of the excised tissue and detection of possible occult early invasion.

PMID- 12497681
TI  - Influence of NaMFP therapy on plasma leptin concentration in postmenopausal
      women.
AB  - OBJECTIVE: To investigate the effect of a low dose of fluoride on the plasma
      leptin concentration in postmenopausal women. STUDY DESIGN: One hundred one
      healthy, postmenopausal women participated in this comparative study. To evaluate
      the influence of NaMFP treatment and body mass index (BMI) on leptin
      concentrations, patients were allocated to one of four groups: postmenopausal
      women (1) on NaMFP with BMI < 25 (n = 29), (2) on NaMFP with BMI > or = 25 (n =
      26), (3) not on NaMFP with BMI > or = 25 (n = 24) and (4) not on NaMFP with BMI <
      25 (n = 22). Plasma leptin levels were measured before and 12 months after the
      initiation of NaMFP or, in groups 3 and 4, after the start of the study. Ninety
      eight women completed the study. RESULTS: There were significant differences in
      leptin concentrations at baseline and 12 months between NaMFP users with BMI > or
      = 25 and BMI < 25 and between women not taking NaMFP with BMI > or = 25 and BMI <
      25 (group 2 versus 1 and 3 versus 4). After controlling for BMI, the use of NaMFP
      was not found to be related to the leptin value (group 1 versus 4 and group 2
      versus 3). Although plasma leptin concentrations tended to be decreased slightly
      at 12 months in NaMFP users, this decrease was not statistically significant (P =
      .065). CONCLUSION: Leptin concentrations are significantly higher in obese,
      postmenopausal women than in nonobese, postmenopausal women. Plasma leptin
      concentrations are slightly but nonsignificantly influenced by long-term, low
      dose fluoride treatment. Further studies are needed to elucidate the role of
      NaMFP on plasma leptin concentrations.

PMID- 12497682
TI  - Severe preeclampsia and the very-low-birth-weight infant. The controversy over
      delivery mode continues.
AB  - OBJECTIVE: To compare the effects of labor induction with those of cesarean
      delivery without labor on neonatal outcome in pregnancies complicated by severe
      preeclampsia and delivery of very-low-birth-weight infants. STUDY DESIGN: This
      retrospective study covered 400 singleton, live-born infants who weighed 750
      1,500 g at birth and were delivered because of severe preeclampsia. Outcome in
      infants delivered by cesarean section without labor was compared with that in
      infants exposed to labor induction. RESULTS: Of the 400 women with severe
      preeclampsia who delivered infants between 750 and 1,500 g; 280 (70%) had labor
      induced, and 120 (30%) delivered without labor. Vaginal delivery was accomplished
      by 182 (65%) women in the induced group. Apgar scores of < or = 3 at five minutes
      was more common in the labor-induced group (6% versus 3%, P = .04); however,
      other neonatal outcomes, including respiratory distress syndrome, ventricular
      hemorrhage, sepsis, seizures and neonatal death, were similar in the two groups.
      Data analysis of the induced group did not reveal an association between route of
      delivery and neonatal outcome. Outcome in both groups was satisfactory at six
      months. CONCLUSION: Induction of labor in women with severe preeclampsia is not
      harmful to very-low-birth-weight infants and appears to be a safe mode of
      delivery.

PMID- 12497683
TI  - Effect of labor induction on cesarean section rates in diabetic pregnancies.
AB  - OBJECTIVE: To determine if induced labor increases the incidence of cesarean
      delivery in pregnancies complicated by diabetes. STUDY DESIGN: This retrospective
      cohort study of pregnancies complicated with diabetes involved data from birth
      certificates reported to the New Mexico Department of Health between January 1996
      and December 1999. RESULTS: There were 108,487 births, with 3,392 (3.1%) in women
      with diabetes. As compared to those without diabetes, this group had an almost
      twofold-increased risk of primary cesarean delivery (20.3% versus 11.3%; OR 2.00;
      95% CI 1.83, 2.19). The risk of primary cesarean delivery in diabetic women was
      lower in the presence than in the absence of induced labor (17.7% versus 21.9%;
      OR .77; 95% CI .50, 0.89). This association continued after controlling for birth
      weight > or = 4,000 g, breech presentation, twins, maternal age > 35 and
      gestational age > 42 weeks. CONCLUSION: Induction of labor was not an independent
      risk factor that could explain the higher cesarean delivery rate in diabetic
      pregnancies.

PMID- 12497684
TI  - Primary peritoneal carcinoma presenting as adenocarcinoma on a Pap smear. A case
      report.
AB  - BACKGROUND: Primary peritoneal carcinoma is an uncommon malignancy that usually
      presents with gastrointestinal symptoms from abdominal carcinomatosis. CASE: A
      postmenopausal woman presented with vaginal bleeding and adenocarcinoma cells on
      a Pap smear. Colposcopy, endocervical and endometrial curettage, mammography,
      colonoscopy and pelvic ultrasound were all normal. Computed tomography revealed a
      large omental cake and ascites, and the CA-125 level was elevated, 2,907 IU/mL.
      Exploratory laparotomy revealed a primary peritoneal carcinoma with abdominal
      carcinomatosis. CONCLUSION: Primary peritoneal carcinoma should be considered in
      the differential diagnosis of adenocarcinoma cells arising on a Pap smear in the
      absence of cervical and endometrial cancer.

PMID- 12497685
TI  - Uterus didelphys with cervical agenesis associated with adenomyosis, a leiomyoma
      and ovarian endometriosis. A case report.
AB  - BACKGROUND: Elevated level of serum CA-125 was detected in a 48-year-old woman
      who was diagnosed with a lateral fusion defect in association with congenital
      agenesis of the uterine cervix. This unusual case combined two developmental
      anomalies of the mullerian duct. CASE REPORT: A 48-year-old woman consulted our
      outpatient department due to persistent abdominal pain for six months. Bimanual
      pelvic examination showed absence of the cervix, an anteverted uterus and a 6-cm,
      left adnexal mass. Ultrasound and computed tomography revealed a uterus didelphys
      with a 3-cm cystic mass over the right ovary. Serum level of CA-125 was 641.4
      U/mL. The patient underwent exploratory laparotomy, and total abdominal
      hysterectomy with bilateral salpingo-oophorectomy was performed. Pathology
      confirmed adenomyosis and a leiomyoma of the uterus with functional endometrium
      in conjunction with endometriosis of the right ovary. CONCLUSION: Multiple
      mullerian anomalies associated with adenomyosis and endometriosis should be
      considered in patients presenting with primary amenorrhea. Thorough evaluation,
      careful planning, fertility preservation and postoperative outcomes should be
      reviewed.

PMID- 12497686
TI  - Concomitant urethral and uterovaginal prolapse in a postmenopausal woman. A case
      report.
AB  - BACKGROUND: Urethral prolapse is frequently encountered in girls. Although its
      occurrence in elderly women is not rare, little published information exists
      regarding this clinical condition or its management. CASE: A 90-year-old woman
      (gravida 1, para 1) with a four-year history of intermittent vaginal bleeding had
      both urethral and uterovaginal prolapse. The condition was initially managed
      conservatively with estrogen and a pessary. Ultimately, surgical intervention was
      required for complete resolution. CONCLUSION: Urethral prolapse can occur in
      elderly women and may present concomitantly with other forms of pelvic floor
      dysfunction such as uterovaginal prolapse. Conservative treatment with estrogen
      is partially effective in reducing the size of the urethral prolapse and may
      point to hypoestrogenism as one potential cause of this condition in elderly
      women. However, surgical management may ultimately be required for complete
      resolution of these problems, even in medically compromised patients.

PMID- 12497687
TI  - Conservative therapy for malignant struma ovarii. A case report.
AB  - BACKGROUND: Thyrocarcinoma in struma ovarii is rare. Treatment options include
      salpingo-oophorectomy, complete surgical resection and/or adjuvant therapy. CASE:
      A young woman presented with a pelvic mass. Unilateral salpingo-oophorectomy was
      performed with findings of malignant thyroid tissue. No adjuvant therapy was
      administered. CONCLUSION: Conservative surgical approaches should be considered
      in patients with malignant struma ovarii who wish to maintain fertility.

PMID- 12497688
TI  - Malignant mixed mesodermal tumor in a young woman with polycystic ovary syndrome.
      A case report.
AB  - BACKGROUND: Malignant mixed mesodermal tumors (MMMTs) are uncommon, highly
      aggressive tumors of the uterus composed of both carcinomatous and sarcomatous
      elements, both likely to be derived from the same original stem cell. There is a
      strong association between endometrial adenocarcinoma and polycystic ovary
      disease. However, only two cases of MMMT occurring in women with polycystic
      ovaries have been reported. CASE: A 36-year-old woman with polycystic ovary
      disease developed an MMMT of the endometrium. CONCLUSION: Some cases of MMMT may
      be estrogen related.

PMID- 12497689
TI  - Fibroadenoma of the vulva. A report of two cases.
AB  - BACKGROUND: Vulvar fibroadenoma is a rare entity. It has been proposed that the
      tissue of origin is either ectopic breast tissue or vulvar mammarylike glands.
      Sporadic examples of benign and malignant vulvar tumors arising from such glands
      have been previously reported. CASES: We recently encountered two cases of vulvar
      fibroadenoma, one in a 29-year-old woman and one in a 42-year-old woman, with
      both neoplasms presenting clinically as vulvar cysts. CONCLUSION: Fibroadenoma of
      the vulva is an uncommon lesion histologically similar to fibroadenoma of the
      breast. Clinicians need to be aware that the lesion can occur in this location.

PMID- 12497690
TI  - Fetal meconium peritonitis in the infant of a woman with fulminant hepatitis B. A
      case report.
AB  - BACKGROUND: Simultaneous fulminant maternal hepatitis B infection and fetal
      meconium peritonitis has never been reported before in the English-language
      literature. CASE REPORT: Fetal meconium peritonitis was detected at 32 weeks'
      gestation in a 21-year-old woman suffering from fulminant hepatitis. Fulminant
      hepatitis B was confirmed by clinical observation and serologic examination
      results. The course was also complicated with preterm labor. The fetus was
      diagnosed with meconium peritonitis prenatally. Because of failed tocolytic
      treatment, the fetus was delivered vaginally. Both the mother and fetus received
      intensive care, and the mother recovered. In contrast, the fetus's course
      worsened due to progressive abdominal distension. Although exploratory laparotomy
      was attempted, the operation was not successful. The infant died five days after
      birth. CONCLUSION: Recognition of the predisposing factors in fetal meconium
      peritonitis and immediate referral to a tertiary medical center, where
      specialists are available, could help physicians determine an accurate diagnosis
      and might improve prognosis.

PMID- 12497691
TI  - Management of intramedullary endometriosis of the conus medullaris. A case
      report.
AB  - BACKGROUND: Few data exist on treating spinal cord endometriosis. CASE: Total
      excision of the endometriotic lesion, followed by a bilateral oophorectomy and
      aromatase inhibitor therapy, led to a clinical improvement. CONCLUSION: Attempts
      at total removal of spinal cord endometriosis may be safer after achieving
      pharmacologic control.

PMID- 12497692
TI  - Viable intrauterine pregnancy with acute salpingitis progressing to septic
      abortion. A case report.
AB  - BACKGROUND: A viable intrauterine pregnancy with salpingitis has been reported
      rarely. CASE: A 27-year-old woman at 10 weeks' gestation developed abdominal
      pain, fever, leukocytosis, peritoneal signs, closed cervix and a viable
      pregnancy. Progression from acute salpingitis to septic abortion was documented.
      CONCLUSION: Acute salpingitis in the presence of a viable pregnancy warrants
      aggressive intervention.

PMID- 12497693
TI  - Possible maternal inheritance of a common obstructive urinary tract anomaly.
      Report of a case of a woman with multiple urinary tract infections and two sons
      with posterior urethral valves.
AB  - BACKGROUND: Posterior urethral valves (PUVs) are the most common cause of lower
      urinary tract obstruction in boys. Several prior reports have described PUV in
      siblings and twins, often with a variable phenotype. CASE: PUVs were found in two
      brothers. The first child had developmental delay, while the second had a
      branchial cleft cyst and an anteriorly rotated right ear. The children's mother
      had a history of numerous urinary tract infections of unknown etiology.
      CONCLUSION: Though most cases of PUV appear to be sporadic, there are reports
      that suggest a partial genetic etiology, as our case suggests.

PMID- 12497694
TI  - Symposium on human subjects research: redux.

PMID- 12497695
TI  - From the lab to the clinic: one investigator's journey.

PMID- 12497696
TI  - Obtaining informed consent for research: a model for use with participants who
      are mentally ill.

PMID- 12497697
TI  - Evidence, belief, and action: the failure of equipoise to resolve the ethical
      tension in the randomized clinical trial.

PMID- 12497698
TI  - RAC oversight of gene transfer research: a model worth extending?

PMID- 12497699
TI  - Financial conflicts of interest in human subjects research: the problem of
      institutional conflicts.

PMID- 12497700
TI  - Universality and its limits: when research ethics can reflect local
      circumstances.

PMID- 12497701
TI  - The invisible hand in clinical research: the study coordinator's critical role in
      human subjects protection.

PMID- 12497702
TI  - Professionalism in forensic bioethics.

PMID- 12497703
TI  - Solid organ donation between strangers.

PMID- 12497704
TI  - Commentary: making the most of strangers' altruism.

PMID- 12497705
TI  - All donations should not be treated equally: a response to Jeffrey Kahn's
      commentary.

PMID- 12497706
TI  - Reforming medical ethics education.

PMID- 12497707
TI  - ADA: Supreme Court denies cert to ADA duty of accommodation case.

PMID- 12497708
TI  - Assisted suicide: court strikes down Ashcroft directive.

PMID- 12497709
TI  - First Amendment: contractor physician's speech is protected.

PMID- 12497710
TI  - FMLA: Department of Labor overstepped authority.

PMID- 12497711
TI  - Patient confidentiality: Illinois Supreme Court upholds consent forms for release
      of records.

PMID- 12497712
TI  - Privacy: users of pharmaceutical websites.

PMID- 12497713
TI  - Products liability: the fate of the learned intermediary doctrine.

PMID- 12497714
TI  - Transplant tissue: Cryolife human soft tissue implants recalled.

PMID- 12497715
TI  - [Anti-infective agents and bacterial resistance, monitor, eradicate or avoid
      resistance?].

PMID- 12497716
TI  - [The need to optimize growth hormone treatments].

PMID- 12497717
TI  - [Arguments in favor of a link between hyperhomocysteinemia and dementia].

PMID- 12497718
TI  - [Antifungal treatments].
AB  - THE SITUATION: Invasive fungal infections are increasing and are associated with
      high rates of morbidity and mortality. The recent emergence of new molecules and
      antifungal classes raises the hope of new therapeutic perspectives. SECOND
      GENERATION TRIAZOLES: Voriconazole, ravuconazole and posaconazole have a broader
      spectrum than the first generation, including notably Aspergillus species and
      Candida species, resistant to fluconazole. ECHINOCANDINES: Caspofongine and
      micafongine belong to a new family of antifungals: echinocandines. With a
      different mechanism of action, they affect the fungal wall. PRESENT RESEARCHES:
      Are oriented towards the exploration of prophylaxis in patients at risk and, in
      particular, towards antifungal combinations. However, regarding the latter, in
      vitro studies and experiments in animals are rare and sometimes contradicting,
      and clinical trials are almost inexistent.

PMID- 12497719
TI  - [Risk factors and treatment of methicillin-resistant Staphylococcus aureus
      infections].
AB  - METICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS INFECTIONS (MRSA): The maintenance of
      a catheter in febrile neutropenic patients with MRSA bacteremia is justified,
      except when the latter persists 2 to 3 days after the initiation of treatment.
      Prior administration of fluoroquinolones (levofloxacine or ciprofloxacine) is a
      risk factor significantly associated with the isolation of MRSA. Meticillin
      resistance is not a factor of mortality in HIV-infected patients exhibiting S.
      aureus bacteremia. Surveillance blood cultures represent a simple method for
      identifying patients at high risk of secondary foci. INFECTIONS WITH GLYCOPEPTIDE
      INTERMEDIATE MRSA (HETERO-GISA): In liver transplant recipients, the risk of
      acquiring a hetero-GISA is not associated with prior MRSA infection nor prior
      glycopeptide treatment. It is significantly associated with the occurrence of an
      infectious episode in the weeks preceding the transplant and with the
      administration of beta-lactams during the previous two months. Mortality is not
      increased in patients with hetero-GISA. NEW ANTIBIOTICS: Linezolide and
      quinupristine-dalfopristine are new agents available for the treatment of MRSA
      infection. Other antibiotics under development have demonstrated their activity:
      lipopeptides (daptomycin), semi-synthetic glycopeptides (oritavancin,
      dalbavancin), glycylglycines (tigecyclin), carbapenems (CP5609), and
      cephalosphorins (LB 11058). ANTIBIOTIC COMBINATIONS: Various studies have shown
      that antibiotic combinations must be used with care in the treatment of MRSA and
      GISA infections (glycopeptide intermediate strains) because of the antagonism
      between molecules belonging to different families.

PMID- 12497720
TI  - [Update on Acinetobacter baumannii].
AB  - RESISTANCE TO IMIPENEM: The increase in the prevalence of A. baumannii resistance
      is worrying because of the diversity of the enzymes implicated in the resistance
      and its epidemic diffusion that is always difficult to handle. BROAD SPECTRUM
      BETA-LACTAMASE: Still rare in Acinetobacter, a broad spectrum beta-lactamase has
      been demonstrated in a strain isolated during a urinary infection and at the
      origin of an outbreak. RISK FACTORS: Other than the classic risk factors, a
      survey regrouping the data from 28 Spanish hospitals showed that hospitalisation
      in an intensive care unit and the administration of an inappropriate
      antibiotherapy are two risk factors of mortality during Acinetobacter infections.
      DEPENDING ON THE PRODUCTION OF SLIME: An antibiotherapy must be administered
      earlier in strains producing slime than in strains that do not. TO FIGHT
      ACINETOBACTER: It is essential to break the epidemic chain. In addition to this
      priority measure, a policy of correct antibiotic use must be installed.

PMID- 12497721
TI  - [Community-acquired bacterial infections].
AB  - CORTICOSTEROIDS IN BACTERIAL MENINGITIS: A randomised multicentre study on
      meningitis in adults versus a placebo showed significant benefits of corticoids
      in terms of reduction in mortality and neurological complications. These results
      were essentially observed in pneumococcal infections. THE INTEREST IN MONITORING
      BLOOD CULTURES: Several works on Staphylococcus aureus bacteremia have confirmed
      the necessity of monitoring hemocultures, 48-72 hours following initiation of
      treatment. The persistence of bacteremia strongly suggests the poor prognosis and
      endocardial grafting should be envisaged. CARDIOVASCULAR RISK: Persisting
      Salmonella enterica bacteremia in an adult aged over 50 must lead to search for a
      cardiovascular infection, notably mycotic aneurism, in view of the risk of
      rupture and the necessity of early surgery. This type of infection is observed in
      10 to 23% of cases. BACTERIAL ENDOCARDITIS: The size of the vegetations > 2 cm
      and the neurological complications of embolic nature are clearly identified as
      predictive factors of death in endocarditis of drug addicts. Early surgery in the
      case of voluminous vegetations, including in the right endocardium, is therefore
      discussed. URINARY INFECTIONS: A randomised study against a placebo in
      asymptomatic urinary infections of diabetic women showed no significant benefits
      of the antibiotherapy on reducing morbidity.

PMID- 12497722
TI  - [Latest news on fluoroquinolones].
AB  - THE AIMS OF NEW FLUOROQUINOLONES: Are to widen the antimicrobial spectrum and
      eventually reach anaerobic bacteria, to increase the activity on resistant Gram
      positive bacteria and to enhance the affinity of the molecule for the target
      enzymes of the bacteria THE EXPECTATIONS WITH THE NEW QUINOLONES: Globally, the
      tests conducted show far superior activity than that of the agents used for
      comparison. CONCERNING THE OLDER FLUOROQUINOLONES: Despite the threat of
      emergence of resistance in pneumococci, questions are raised on the clinical
      correspondence of the microbiological data obtained, notably with the rates of
      therapeutic failure, observed in patients exhibiting strains with supposedly high
      MICs.

PMID- 12497723
TI  - [Concentrations preventing resistance mutations against fluoroquinolones].
AB  - AS A PRECAUTION: The new fluoroquinolones are clearly active on both Gram
      negative and Gram positive bacteria and on intracellular and strictly anaerobic
      bacteria, with excellent pharmacological properties. Nevertheless, there is a
      risk of resistant mutants appearing due to selective pressure, that would rapidly
      delete their activity. CONCENTRATIONS AVOIDING MUTATIONS: Among the definitions
      envisaged for the concept of a concentration that would prevent mutations or
      "mutation preventing concentration" (MPC), the most frequently retained is the
      concentration at which no mutant appears in the presence of a high inoculum.
      VALUES OF CONCENTRATIONS PREVENTING MUTATIONS: These have been established for
      Gram negative bacilli, for staphylococci methicillinsusceptible and for
      pneumococci. The MPC values are not correlated with those of the minimum
      inhibitory concentration (MIC), they are related to the bactericidal potential of
      fluoroquinolones. IN PRACTICE: Despite their limits, the MPC are of major
      interest for the prevention of mutants, which are always dangerous, since their
      underlying resistance mechanism is eventually unknown.

PMID- 12497724
TI  - [Peptide-deformylase inhibitors, a new class of antibiotics].
AB  - PEPTIDE-DEFORMYLASE: During protein synthesis in bacteria, a transformylase
      coding the fmt gene provides a formyl group on methionine before binding to the
      ARNm-ARNt complex. This tormylated methionine initiates the protein synthesis.
      The adjunction of an amino acid to the peptide chain leads to a peptide
      associated with a formylated methionine. The final stage requires a metallo
      enzyme, peptide deformylase, which releases the peptide and regenerates the
      methionin. PEPTIDE-DEFORMYLASE INHIBITORS (PDF): Often rejected by the efflux
      pumps of Gram negative bacteria, PDF inhibitors are administered in the form of
      pro-drugs, capable of acting even in the bacteria that have lost their
      transformylase gene. TWO PRODUCTS: These are VCR 4887 developed by Versicor and
      Novartis and BB 83698 developed by British Biotechnology Genesoft. They are
      presently in the process of clinical predevelopment. They represent an important
      innovation and widen the range of new antibiotic classes.

PMID- 12497726
TI  - [Psychopathology of traveling].

PMID- 12497725
TI  - [Smallpox, bioterrorism agent].
AB  - A CONSIDERABLE RISK: Among the infectious agents that might be used as terrorist
      weapons, the smallpox virus represents a sufficiently high risk, which is
      difficult to manage and must be seriously taken into account. FROM A
      MICROBIOLOGICAL POINT OF VIEW: Two viral strains of the smallpox virus, which
      belong to the Poxviridae and orthopoxvirus-type families, are known. They are
      associated with various clinical presentations of smallpox, i.e., variola major
      and variola minor or "alastrim". VARIOLA MAJOR: Five clinical forms of varying
      prognosis are described. Common smallpox, haemorrhagic smallpox (the most severe
      form of the disease), mild smallpox (predominantly observed in vaccinated
      patients), flat-type smallpox (defined by coalescent and slowly progressive
      lesions) and so-called "sine eruptione" smallpox. VARIOLA MINOR: This form is not
      as severe as variola major and the mortality rate is lesser. DIAGNOSIS: Smallpox
      must be systematically evoked on clinical elements and confirmed by electronic
      microscopy of a sample of liquid from a vesicle or pustule or a scab. The strains
      can be characterised by PCR (Polymerase Chain Reaction). TREATMENT: It is
      symptomatic. Early vaccination, within 4 days following exposure to the virus,
      permits the reduction in mortality by 50%. The only efficient prevention is
      vaccination prior to any exposure to the virus. In the case of a bioterrorist
      attack, the United States and most of the EC countries propose to vaccinate only
      the health professionnals most exposed to the virus and those having contacted
      identified cases.

PMID- 12497727
TI  - Compensation for "pure psychiatric injury": resolution from the Australian High
      Court?

PMID- 12497728
TI  - Legal liability for pain management involving opioid medication: an American
      perspective.

PMID- 12497729
TI  - Review of death investigation and certification in the United Kingdom.

PMID- 12497730
TI  - Enrolled nurses and the administration of medications: to give or not to give?

PMID- 12497731
TI  - Wrongful death claims. Harriton v Stephens. [2002] NSWSC 461. Edwards v Blomeley.
      [2002] NSWSC 460. Waller v James [2002] NSWSC 462.
AB  - Studdert J in all three cases went to great length to summarise the global
      judicial position of "wrongful life" claims. He did not, however, examine in
      great length how or whether "wrongful life" claims or "wrongful birth" claims are
      reconcilable with tort and common law principles. Although the cases identify the
      difficulty in assessing and quantifying damages, they do not directly address the
      strict legal principles which apply in the assessment of damages. The main
      conclusion of the three judgments was that no duty of care is owed to the
      plaintiff in these circumstances and, even if a duty could be established, the
      impossibility of quantifying damages and public policy considerations warrant the
      rejection of such a claim: "thus conscience does make cowards of us all." The
      significance of the decisions cannot be understand. The decisions deny
      recognition of "wrongful life" claims in circumstances where a disabled person
      has incurred injuries en ventre sa mere (in the mother's womb) as a result of
      infections contracted by a plaintiff's mother or genetic material passed on by a
      plaintiff's parents. Some countries have now legislated for the abolition of
      "wrongful life and birth" suits. In January 2002 the French legislature passed a
      Bill overturning the "wrongful life" decision of the Cour de Cassation in
      Perruche (17 November 2000). As the issue now falls for ultimate determination by
      the French Senate, the French pro-life movement continues to lobby for the
      prohibition of "wrongful birth" suits as well. Furthermore, eight States in the
      United States have prohibited either one or both actions and the State of
      Michigan prohibited both actions in 2001. It is likely that all three cases will
      be appealed. The appeal in Harriton will re-examine the viability of a "wrongful
      life" claim in Australia whereas the cases of Edwards and Waller still need to
      determine the "wrongful birth" claims brought by the plaintiffs' parents. It is
      likely that the latter two cases will not be determined until the High Court has
      considered the Queensland "wrongful birth" case of Melchior v Cattanach, expected
      to be late in 2002.

PMID- 12497732
TI  - The right not to know and coronary angiography: is the common law of Australia
      consistent with patients' wishes?
AB  - In "The Right Not to Know: Patient Autonomy or Medical Paternalism?" (2000) 7 JLM
      286 Judy Gutman qualitatively examined the direction of the law relating to the
      duty of medical practitioners to disclose information to their patients about
      risks associated with medical treatment. Prompted by theoretical issues raised in
      that article, a quantitative study was performed. The study focused on the wishes
      of patients referred for coronary angiography regarding information about the
      risks inherent in that procedure. The results of the study contribute to the
      ongoing academic discussion about risk disclosure and consent to medical
      treatment and demonstrate a need for further empirical research in the area. The
      study also highlights the desirability of clinical medical practice conforming to
      the tenets of the common law and vice versa.

PMID- 12497733
TI  - Cervical manipulation--how might informed consent be obtained before treatment?
AB  - This article discusses methods and mediums of obtaining informed consent in
      physiotherapy clinical practice, specifically in relation to cervical
      manipulation. Whilst cervical manipulation is a useful method of treatment for
      spinal joint pain and dysfunction, it has also been shown to be ineffective or
      even positively harmful. Legal precedents have set boundaries for informing
      patients of such adverse consequences. However, a degree of uncertainty exists in
      the physiotherapy profession, as in other health care professions, as to how to
      obtain informed consent in a busy clinical setting in order to discharge the
      legal duties owed. Obtaining meaningful informed consent in clinical practice
      raises issues of patient comprehension, memory and decision-making capacity. A
      large quantity of research directed at enhancing patient understanding has been
      undertaken in recent years. The important findings are that a variety of
      communication methods and mediums need to be employed in both providing
      information and assessing patient understanding. A combination of verbal, written
      and audiovisual information provides patients with maximum opportunity to be
      involved in treatment decisions.

PMID- 12497734
TI  - Supervisory responsibilities of specialists.
AB  - The public hospital system in New Zealand is heavily reliant on junior doctors
      for the day-to-day provision of medical care to hospital patients. Specialists
      have supervisory responsibilities for junior doctors during the day, as leaders
      of clinical teams, and after hours when they are on call. Due to changes in the
      health system over the past 20 years, there has been a change in the nature and
      level of specialist supervision required. Under the Code of Health and Disability
      Services Consumers' Rights, where aspects of clinical care are delegated to
      junior doctors, specialists have a duty to provide supervision with reasonable
      care and skill and in accordance with professional standards.

PMID- 12497735
TI  - Surrogacy: ill-conceived rights.
AB  - Despite the fact that altruistic surrogacy arrangements occur in Australia, the
      law does not adequately regulate many important aspects of such arrangements.
      Failure to regulate surrogacy leaves infertile couples contemplating such
      treatment, as well as clinics dealing with them, in an unsatisfactory position.
      This article examines the law that operates in Australian States and Territories
      (and the problems associated with them) as well as in New Zealand, the United
      Kingdom and some United States jurisdictions, considers whether the argument
      against surrogacy arrangements can be legitimately sustained in modern times, and
      examines some regulatory regimes that seem to be working satisfactorily elsewhere
      in the world.

PMID- 12497736
TI  - Euthanasia: why it doesn't matter (much) what the doctor thinks and why there is
      no suggestion that doctors should have a duty to kill.
AB  - A major reason that The Netherlands has taken a different approach to the rest of
      the world on such a fundamental moral issue is that the courts and legislature in
      that country have accorded the interests of doctors a cardinal role in the
      euthanasia debate. This article argues that the interests of doctors are of only
      incidental and peripheral relevance in relation to the moral status of
      euthanasia. The moral status of euthanasia has little to do with the preparedness
      of doctors to administer the lethal injection or their general attitude towards
      the practice. Euthanasia is principally about the interests of the patient and
      the impact that the practice may have on the community in general, not preserving
      the conscience or improving the working life of doctors.

PMID- 12497737
TI  - Implications of legalising euthanasia in The Netherlands: greater regulatory
      control?
AB  - Euthanasia has been decriminalised in The Netherlands for the last 30 years, but
      it was only in April 2001 that the Dutch Parliament legalised voluntary physician
      assisted suicide. The legislation incorporates developments in case law,
      including scope for peer review, and provides common ethical principles for a
      clear system of control over doctors' actions in regard to patients who request
      euthanasia. The legalised regulatory system may prove more effective in
      controlling voluntary and non-voluntary euthanasia in The Netherlands than in
      countries where euthanasia remains illegal.

PMID- 12497738
TI  - Autonomy and the competent patient's right to refuse life-prolonging medical
      treatment--again.
AB  - This article discusses the recent decision of the Court of Appeal of the United
      Kingdom in Re B (Adult: Refusal of Medical Treatment) [2002] 2 All ER 449, which
      confirmed the common law right of a competent patient to refuse medical
      treatment, even though exercise of the right would (and later did) result in the
      patient's own death. Re B indicates that if a competent refusal is not respected,
      health professionals and hospitals face the prospect of awards of damages being
      made against them for unlawful trespass.

PMID- 12497739
TI  - [Postgraduate nephrology teaching in Spain].

PMID- 12497740
TI  - [Macro- and microvascular disease in type 2 diabetes mellitus].

PMID- 12497741
TI  - [The nephrologists and renal polycystic disease].

PMID- 12497742
TI  - [Emerging viruses in nephrology: polyomavirus].

PMID- 12497743
TI  - [The fate of podocytes in proteinuric nephropathies].

PMID- 12497744
TI  - [Differences between the glomerular filtration rate estimated by the MDRD
      equation and the measurement of creatinine and urea clearance in unselected
      patients with terminal renal insufficiency].
AB  - From the results of the Modification of Diet in Renal Disease (MDRD) study, a
      prediction equation for a more accurate estimate of glomerular filtration rate
      (GFR), was developed. The present study ais to compare the GFR estimated by MDRD
      formula and that calculated by the average of creatinine and urea clearances in
      unselected patients with advanced renal failure. The study group consisted of 320
      (163 males) with advanced renal failure not yet on dialysis. Their mean age was
      63 +/- 14 years. Diabetic nephropathy was the most common etiology of renal
      failure (25%). Significant comorbidity was observed in 115 patients. Serum
      creatinine (Cr), urea and albumin were determined in all patients. Creatinine
      (Ccr) and urea clearance (Cu) were calculated on a 24-hour urine collection. The
      GFR was estimated by summing Ccr and Cu, and dividing by two (Ccr-Cu). THe
      clearances were corrected for a body surface area of 1.73 m2. The MDRD formula
      for the estimation of GFR included the following parameters: serum Cr, BUN, age,
      gender and serum albumin. Linear regression analysis and Bland-Altmann plot were
      utilized to establish the degree of correlation and agreement between both
      estimations of GFR. The percent differences between the two estimations of GFR
      was especially analyzed in those subgroups of patients which were not included in
      the MDRD study (patients older than 70 years, diabetics and those with comorbid
      conditions). The mean GFR estimated by Ccr-Cu and by MDRD formula were 10.04 +/-
      3.10 ml/min and 10.55 +/- 3.60 ml/min, respectively (p < 0.0001). The two
      parameters correlated significantly (R = 0.76, p < 0.0001). GFR by the MDRD
      formula tended to overestimate the highest values of Ccr-Cu. The mean percent
      difference between both methods was 6.5 +/- 23.6. MDRD predictive equation
      overestimated significantly Ccr-Cu in patients older than 70 years (mean
      overestimation of 15%), males (10%), diabetics (10%), and mainly in patients with
      comorbidity (17%). In conclusion, the GFR estimated by MDRD formula is very
      similar to Ccr-Cu in young uremic patients without comorbidity. However, major
      discrepancies between these two methods could be observed in older patients, and
      mainly in those with comorbidity.

PMID- 12497745
TI  - [Evaluation of food intake in hemodialysis using a food consumption and appetite
      questionnaire].
AB  - Protein calorie malnutrition is a common complication in chronic hemodialysis
      patients (CHP). Although many factors could promote malnutrition, inadequate
      nutrient intake seems to be one of the most important. An Appetite and Diet
      Assessment Questionnaire (ADAQ) was developed, and we have performed a cross
      sectional study in 44 CHP to investigate its capacity to predict an inadequate
      intake. Dietary evaluation was based on a diet diary-assisted recalls (DDAR). On
      the other hand, the validity of PCR and the differences in the DDAR and ADAQ
      between the days of dialysis and the days without dialysis were studied. The
      predictive value of inadequate intake of the ADAQ and the PCR were analysed with
      the ROC curve. The protein intake was 1.3 +/- 0.3 g/kg/day and the energy intake
      29.2 +/- 0.6 kcal/kg/day. The average PCR was 1.14 +/- 0.3. The ROC curve to
      predict inadequate intake from the ADAQ shows an area under the curve of 0.84 for
      the protein intake and 0.73 for the energy intake. A cut-off ponit of 18 gives a
      sensitivity of 100% and a specificity of 44% for the detection of poor protein
      intake (< 1.2 g/kg/day) and of 74% and 56% for the detection of poor energy
      intake (< 30 kcal/kg/day). The ROC curve to predict inadequate protein intake
      from the PCR obtains an area under the curve of 0.81. The cut-off 1.06 gives the
      best sensitivity (100%) and specificity (64%) for the detection of insufficient
      protein intake. We did not find any significant difference in the DDAR or in the
      ADAQ between the days of dialysis and the days without dialysis. Despite the
      subjective interpretation, the relationship between ADAQ and protein-energy
      intakes analysed by DDAR was highly significant. The questionnaire is simple and
      can therefore be used as a screening rest to detect and correct alterations in
      the diet which could otherwise lead to malnutrition. The determination of PCR
      gives a good sensitivity and specificity for the detection of poor protein
      intake, although the results are modified in anabolic or catabolic states which
      can clinically go undetected. We do not register differences in diet between the
      days of dialysis and the days without dialysis.

PMID- 12497746
TI  - RenaGel efficacy in severe secondary hyperparathyroidism.
AB  - BACKGROUND: Haemodialysis patients frequently have simultaneous hypercalcemia and
      hyperphosphatemia, posing a therapeutic dilemma for the traditional calcium--and
      aluminum--based binders. RenaGel (sevelamer hydrochloride) is an effective
      phosphate binder without changes in serum calcium or aluminum levels. However
      being an expensive medication it is currently used mainly for patients with
      moderate to severe secondary hyperparathyroidism. However most of the previous
      studies have not included patients with severe secondary hyperparathyroidism.
      METHODS: Our purpose is to determine RenaGel binder efficacy in haemodialysis
      patients with severe secondary hyperparathyroidism. As a secondary purpose we
      have followed the variations of parathyroid hormone, serum calcium, serum lipids
      [low- and high-density lipoprotein cholesterol, triglycerides and
      Lipoprotein(a)], uric acid and bicarbonate. All phosphate binders previously used
      were suspended one week before RenaGel prescription. Our study included 18 adult
      haemodialysis patients, with PTHi of 810 +/- 330 pg/ml after the "pre-treatment"
      washout. The binder was administered during 12 weeks, beginning with a mean dose
      of 2.4 +/- 0.4 g daily and adjusted to obtain serum phosphorus under 6.5 mg/dl
      (at the end of the study, the mean RenaGel dose was 2.8 +/- 0.6 g daily. RESULTS:
      The mean changes after RenaGel in serum phosphorus was -0.7 +/- 1.5. mg/dl (P <
      0.05), in serum calcium was 0.5 +/- 1.0 mg/dl (P < 0.05) and in calcium x
      phosphate product of -4.0 +/- 12.4 mg/dl (P = NS). "Post-treatment" the PTHi
      levels remained stable (820 +/- 360 pg/ml vs 810 +/- 330) but serum alkaline
      phosphatase increased (14.3 +/- 14.4 U/l; P < 0.01). LDL cholesterol serum levels
      decreased by -35 +/- 10 mg/dl (P < 0.01), HDL cholesterol showed a trend to
      increase (3.0 +/- 8.1 U/l; P = NS), triglycerides decreased by 38 +/- 56 mg/dl (P
      < 0.05) and Lipoprotein(a) remained stable. Serum albumin increased by 0.1 +/-
      0.2 g/L (P < 0.05), uric acid decreased -0.8 +/- 1.2 mg/dl (P < 0.05) and
      bicarbonate remained unchanged. CONCLUSIONS: RenaGel is an effective phosphate
      binder, even in haemodialysis patients with severe secondary hyperparathyroidism.
      The lipid profile improved with the treatment, with the exception of
      Lipoprotein(a) stabilization. Selection of patients with severe secondary
      hyperparathyroidism at the beginning of RenaGel disposal, for economic reasons is
      debatable, but could be correct.

PMID- 12497747
TI  - [Platelet antiaggregation and hemorrhagic risk in hemodialysis].
AB  - Although the efficacy of antiplatelet therapy in the prevention of cardiovascular
      disease in chronic renal failure is not clearly defined, the improvement in
      cardiovascular disease outcomes in the general population has resulted in its use
      in dialysis patients. The hemorrhagic risk of hemodialysis patients treated with
      anti-platelet agents has not been clarified. Our aim was to evaluate the risk of
      bleeding in hemodialysis patients treated with antiplatelet agents. We assessed
      haemorrhagic complications (HC) in 190 haemodialysis patients from May 1998 to
      August 2000. HC was defined an event that required hospitalization and/or blood
      product transfusion. We evaluated the bleeding events in the haemodialysis
      patients treated with antiplatelet agents and compare them to those not receiving
      this therapy to establish the relative risk of bleeding. Uni- and multivariate
      analyses were conducted to establish the relationships between the haemorrhagic
      event and the following variables: age, gender, time on dialysis, dialysis
      membrane (synthetic or cellulosic), systemic anticoagulation during
      haemodialysis, anaemia (haematocrit), PTH, urea, dialysis efficacy (Kt/V),
      hypertension, diabetes, use of erythropoietin and antisecretory gastric agents.
      RESULTS: 81 (42.6%) were treated with antiplatelet agents. Of the 190 patients,
      28 (14.7%) had 36 haemorrhagic events (10.3 episodes/100 patient-years); 31
      digestive-tract haemorrhages, 4 intracranial and 1 pulmonary. Twenty (24.7%) of
      patients treated with antiplatelet agents had 16.2 episodes/100 patient-years and
      8 (7.3%) without this therapy had 6 episodes/100 patient-years (p < 0.01). In the
      multivariate analysis the antiplatelet therapy remained associated with higher
      probability of having a haemorrhagic complication (OR 3.8; CI 95%: 1.52-9.76, p =
      0.004). Older age (OR 1.03; CI 95%: 1-1.06, p = 0.043), anaemia (OR 0.91; CI 95%;
      0.84-0.9, p = 0.027) and hypertension (OR 2.99; CI 95%: 1.05-8.48, p = 0.039)
      remained associated with the risk of bleeding. 88.2% of patients that had a
      digestive-tract haemorrhage with antiplatelet therapy were receiving an
      antisecretory agent (histamine H2-receptor antagonist or a proton-pump
      inhibitor). CONCLUSIONS: 1) dialysis patients with antiplatelet therapy had a
      higher haemorrhagic risk. The relative risk of bleeding was more than three times
      that of the dialysis population without antiplatelet therapy, and 2) older age
      and hypertension were associated with the haemorrhagic risk. Optimal correction
      of anaemia was associated with less probability of bleeding.

PMID- 12497748
TI  - [Diffuse lymphoproliferative disease after renal transplantation and its relation
      with Epstein-Barr virus. Experience at one center].
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous
      lymphoid proliferations in chronic immunosuppressed recipients which appear to be
      related to Epstein Barr Virus (EBV). Receptor EBV seronegativity, use of
      antilymphocyte antibodies and CMV disease have been identified as risk factors
      that may tigger development of PTLD. We have studied the incidence of PTLD and
      its relationship with EBV in 588 adult renal transplant recipients who were
      transplanted in our hospital from 1988 to 2001. We have also evaluated the
      diagnostic and therapeutic methods used, the risk factors and outcome of the
      patients who developed PTLD. We identified 8 recipients (4 males and 4 females),
      range from 18 to 67 years (mean age 45.6 years) with a median time between
      grafting and PTLD of 4.1 years (0.1-7 years), who developed PTLD (1.3%). Only 1
      patient received OKT3 and had CMV disease, two of them (25%) had been treated
      with hight doses of prednisolone, another was EBV seronegative, but the rest of
      them (50%) had no risk factors. Two patients were diagnosed at autopsy, the
      diagnosis of 5 was based on the histology of biopsy and the last one by CT scans
      of chest-abdomen and cytology. The presence of EBV in the lymphoproliferative
      cells was assessed in 5 out of the 7 studied patients (71.4%). The outcome of our
      recipients was poor. Five out of 8 patients died shortly after diagnosis as a
      direct consecuence of PTLD and another of an infectious complication of the
      treatment (75%). The 2 patients alive started dialysis and 1 of them died 2 years
      later of a non-related cause. In conclusion, PTLD is a relatively frequent
      disease with a poor prognosis in renal transplant patients. It seems to have a
      close relationship with EBV and can develop in the absence of the classical risk
      factors.

PMID- 12497750
TI  - [40-year-old man with primary antiphospholipid syndrome].
AB  - We report the case o a 40-year-old male patient with "primary antiphospholipid
      syndrome" who developed ischemic cerebral infarctions and renal microangiopathy
      with infarction. A review of the literature on renal involvement in the primary
      antiphospholipid syndrome disclosed the differences from the antiphospholipid
      syndrome in the systemic lupus erythematosus. We describe the evolution of the
      patient at eight years, and we emphasize the importance of the treatment with
      warfarin. Also, we review the pathophysiology of severe secondary arterial
      hypertension.

PMID- 12497749
TI  - [Interaction between sildenafil and calcineurin inhibitors in renal transplant
      recipients with erectile dysfunction].
AB  - AIM: Hepatic metabolism of sildenafil uses the same metabolic pathway as the
      calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme.
      The aim of this pilot study was to evaluate the potential interaction between
      sildenafil therapy and circulating levels of cyclosporine and tacrolimus in a
      group of steady-state renal transplant recipients with erectile dysfunction.
      MATERIAL AND METHODS: A prospective pilot study of sildenafil interactions was
      carried out in 9 stable male renal transplant recipients with severe erectile
      dysfunction (mean age 50 +/- 8 years, range 38-64). All patients were receiving
      therapy with calcineurin inhibitors (5 with cyclosporine and 4 with tacrolimus).
      Erectile dysfunction was evaluated by clinical history, physical examination,
      International Index of Erectile Function (IIEF) questionnaire and the nocturnal
      penile tumescence test (RigiScan). Each patient received a first dose of 50 mg of
      sildenafil, one hour before sexual activity and a second dose at 72 hours of 50
      or 100 mg according to the clinical response to the first dose. We evaluated the
      efficacy and safety of sildenafil and the evolution of cyclosporine-tacrolimus
      levels. Cyclosporine and tacrolimus trough whole blood concentrations were
      determined in basal conditions (before starting sildenafil) and on days 1, 4 and
      7 after sildenafil therapy. RESULTS: Eighty-nine percent of patients (n = 8)
      required a complete 100 mg dose of sildenafil. There was a positive clinical
      response in two-thirds of cases (6 patients). In 5 patients (55%) sildenafil
      administration produced a complete response, in one patient the response was
      incomplete, and in the remaining 3 cases (33%) no clinical response was observed.
      Associated side effects included self-limited tachycardia in one patient and mild
      visual disturbances in another. Cyclosporine and tacrolimus levels remained
      stable in all patients. There were no significant differences in circulating
      levels of cyclosporine (basal 120 +/- 47; day 1: 116 +/- 55; day 4: 123 +/- 56
      and day 7: 121 +/- 56 ng/ml p = NS) or tacrolimus (basal 11.6 +/- 1.3; day 1:
      11.9 +/- 1.3; day 4: 11.1 +/- 1.0 and day 7: 11.8 +/- 0.9 ng/ml p = NS) over the
      study period. CONCLUSIONS: Sildenafil therapy is safe and effective for the
      treatment of erectile dysfunction in renal transplant recipients. Recommended
      therapeutic doses of sildenafil did not modify cyclosporine and tacrolimus trough
      blood levels.

PMID- 12497751
TI  - [Recurrence and spontaneous remission of nephrotic syndrome in secondary renal
      amyloidosis].
AB  - Secondary systemic amyloidosis (AA) occurs in association with chronic
      inflammatory disorders and chronic infections. Regression can occur after
      therapeutically induced remission of the underlying disease; spontaneous
      remissions has been reported infrequently. We report a 61 year-old woman, with
      antecedent pulmonary tuberculosis, who developed a nephrotic syndrome at the time
      of a respiratory infection. Renal biopsy showed secondary amyloidosis. Remission
      in the nephrotic syndrome appeared spontaneous, but it recurred in the course of
      pneumonia, and had a second spontaneous remission a maintained at present.

PMID- 12497752
TI  - [Amyloidosis associated with chronic granulomatous disease in a patient with a
      renal transplant and recurrent urinary tract infections].
AB  - Chronic granulomatous disease is a group of syndromes which share a defect in a
      component of the phagocyte NADPH-oxidase complex. Without this enzyme activity,
      phagocytic cells cannot produce superoxide, peroxide, and other potent
      microbicidal radicals, and are less able to kill ingested pathogens. The clinical
      picture is characterised by recurrent life-threatening bacterial and fungal
      infections and abnormal tissue granuloma formation. On the other hand,
      amyloidosis is a systemic disease with renal involvement occurring in the
      majority of cases. Recurrent amyloidosis is a rare but well documented event in
      renal transplant recipients. However, graft loss secondary to amyloidosis has
      been noted infrequently. In addition, de novo amyloidosis has not been previously
      associated with graft loss. We report here a renal transplant recipient with
      chronic granulomatous disease and history of recurrent urinary tract infections,
      who developed nephrotic syndrome and progressive renal insufficiency secondary to
      de novo AA amyloidosis leading to graft loss 66 months after transplantation.

PMID- 12497753
TI  - [The added value of a structured evaluation of patients with vascular disease].
AB  - In 3 patients, 2 women aged 21 and 34 years and a man aged 56 years, with
      complaints related to wide-ranging and extensive vascular conditions, an organ
      specific diagnostic approach and treatment did not lead to the correct diagnosis
      of the underlying clinical condition. Hereafter a structured, partly protocol
      based approach was started which considered the entire vascular system and risk
      factors for vascular disease. The youngest women died a few years later due to
      ventricular fibrillation, while the two other patients were assisted in reducing
      those risk factors that could be influenced. As a result, the planned bypass
      operation was no longer necessary for the male patient. A structured evaluation
      by a multidisciplinary team can optimise the care of these patients. The basis of
      such a team consists of a vascular specialist and vascular nurse-practitioner,
      both of whom should have specific knowledge of risk factors, aetiology, life
      style intervention and treatment of these disorders.

PMID- 12497754
TI  - [Systematic reviews in practice. X. Searching, selecting and the methodological
      assessment of diagnostic evaluation research].
AB  - Literature concerning the value of diagnostic tests is poorly indexed in
      electronic bibliographical databases. An extensive, sensitive and specific search
      strategy for evaluation of a diagnostic test in Medline is a combination of key
      words or text words concerning the diagnostic test with: 'sensitivity and
      specificity' (exploded), 'mass screening' (exploded), 'reference values', 'false
      positive reactions', 'false negative reactions', 'specificit$.tw',
      'screening.tw', 'false positive$.tw', 'false negative$.tw', 'accuracy.tw',
      'predictive value$.tw', 'reference value$.tw', 'roc$.tw' or 'likelihood
      ratio$.tw'. Inclusion and exclusion criteria select publications which meet
      certain minimum requirements, such as the presence of an accepted reference
      standard, a clear definition of 'diseased', and the presence of a suitable
      outcome measure. The methodological assessment list should contain a number of
      validity criteria as well as a number of criteria by which to measure the extent
      to which the study results can be generalised. Important assessment criteria that
      may affect the diagnostic value of the test are: study design, blinding, use of
      different reference standards, the absence of details about the diagnostic
      criteria for the diagnostic test and insufficient information about the study
      population.

PMID- 12497755
TI  - [Anticoagulant treatment of patients with atrial fibrillations: dependent on age
      and other risk factors for thromboembolism].
AB  - Atrial fibrillation is a common arrhythmic disorder which is becoming
      increasingly prevalent among the elderly. Atrial fibrillation is an independent
      risk factor for ischaemic stroke. Patients with hypertension, heart failure,
      diabetes, age older than 65 years, previous thromboembolisms, left atrial
      enlargement and left ventricular dysfunction have an increased risk. Coumarins
      (with a target international normalised ratio (INR) of 2.0 to 3.0) are the
      treatment of first choice in patients with atrial fibrillation. In young patients
      without additional risk factors, acetyl salicylic acid provides sufficient
      protection. The management of anticoagulant therapy during electric cardioversion
      in the acute phase of an ischaemic stroke and during elective surgical
      interventions, is still a subject of clinical research.

PMID- 12497756
TI  - [Revised terminology for allergies and related conditions].
AB  - The European Academy of Allergology and Clinical Immunology has proposed a
      revised terminology for allergic and allergy-related reactions that can be used
      independently of target organ or patient age group. The proposed terminology is
      based on the present knowledge of the mechanisms which initiate and mediate
      allergic reactions. 'Hypersensitivity' is an umbrella term, 'allergy' involves a
      hypersensitivity reaction which is initiated by an immunological mechanism, and
      'atopy' is an individual or familial tendency to produce IgE antibodies in
      response to low doses of allergens, and is accompanied by the typical symptoms or
      asthma rhino-conjunctivitis or eczema/dermatitis. Each condition should be
      categorised as 'allergic/not allergic', and the allergic conditions should be
      further categorised as 'IgE-mediated/non IgE-mediated' (sometimes: 'IgE
      associated'). Terms which are no longer in use include: 'idiosyncrasy' (this will
      now become 'hypersensitivity'); 'pseudo-allergy' ('non-allergic
      hypersensitivity'); 'extrinsic', 'intrinsic', 'endogenous' and 'exogenous asthma'
      ('allergic' (possibly 'IgE-mediated') and 'non-allergic asthma'); 'atopic eczema'
      ('atopic eczema/dermatitis syndrome': 'allergic (possibly 'IgE-mediated') or 'non
      allergic'); 'intrinsic' and 'cryptogenic variants of eczema' ('non-allergic
      atopic eczema/dermatitis syndrome'); 'food intolerance' ('non-allergic food
      hypersensitivity') and 'anaphylactoid reaction' ('non-allergic anaphylaxis').

PMID- 12497757
TI  - [Diagnostic image (116). A man with acute exanthema. Epstein-Barr virus
      infection].
AB  - A 19-year-old man presented with a rash, several days after antibiotic therapy
      for pharyngitis. Such a rash is highly suggestive of an acute viral infection;
      Epstein-Barr virus infection was confirmed serologically.

PMID- 12497758
TI  - [From gene to disease; adrenocortical insufficiency, achalasia and disrupted tear
      secretion: Allgrove syndrome].
AB  - Allgrove syndrome (triple A syndrome) is an autosomal recessive disorder
      characterised by adrenocortical insufficiency, achalasia and alacrima. Patients
      also suffer from diverse neurological disorders. Allgrove syndrome is caused by
      mutations in the AAAS gene located at chromosome 12q13, which encodes for a
      tryptophan-aspartic acid (WD) repeat protein (aladin). The exact function of this
      protein is still not known.

PMID- 12497759
TI  - [Correlation between prenatal ultrasound diagnosis and findings from autopsies or
      neonatal operations due to structural congenital heart defects; a retrospective
      analysis].
AB  - OBJECTIVE: To determine the contribution of the prenatal ultrasound diagnosis of
      structural congenital heart defects to the care of patients requiring surgery for
      their condition in the neonatal period. DESIGN: Retrospective. METHOD: During the
      period January 1991-June 1999, data were collected from two groups of children.
      One group had a structural heart defect diagnosed prenatally and the other
      underwent a neonatal operation due to a heart defect. In the prenatal group, the
      management and follow-up were analysed, whilst in the surgery group, the extent
      to which ultrasound investigation had been performed and whether there was a
      relationship between prenatal diagnosis and the severity of acidosis were
      analysed. RESULTS: A structural heart defect was found through prenatal
      ultrasound in 170 children and 64% of these prenatally diagnosed patients died
      before or immediately after birth, or the pregnancy was aborted. 14% underwent
      surgery within 31 days post partum. This last category formed an overlap with the
      surgery group. The surgery group contained 191 patients, who required surgery in
      the neonatal period, including 24 from the prenatal group. In total, 87% had no
      prenatal diagnosis. In the group with a prenatal diagnosis pre-operative lactate
      values were significantly lower. CONCLUSION: The heart defect was only diagnosed
      prenatally in 13% of the patients from the surgery group, although this would
      have been technically feasible in 46%. Better prenatal diagnosis of heart disease
      could contribute to a better counselling of parents in their choice between
      abortion, conservative treatment or emergency surgery. In the case of emergency
      surgery, prenatal detection might lead to a decrease in morbidity and mortality.

PMID- 12497760
TI  - [Hospital care at home; a review of the literature on the effects of a form of
      transmural care].
AB  - OBJECTIVE: To evaluate the effects of hospital at home on health outcomes and
      quality of life of patients and carers; to evaluate the costs of this form of
      care and the experiences of the (para)medics involved. DESIGN: Literature study.
      METHOD: Using Medline, EMBASE-Excerpta Medica, Sci-search and Cinahl, a search
      was carried out for Dutch- and English-language studies from 1990-2001 which
      compared hospital at home with conventional inpatient care. RESULTS: Twenty-seven
      (randomised) controlled trials and cross-over studies from seven different
      countries were found, which resulted in 37 publications. No differences were
      found in health outcomes between patients allocated to hospital at home and
      inpatient care, providing there was careful patient selection and the home met a
      number of basic conditions. Patients and their carers rated hospital at home
      positively. The expected reduction in costs to the health services was
      disappointing. Good organisation, communication and funding were essential
      boundary conditions to the success of this form of care. Health benefits appear
      to be primarily attained with schemes designed to avoid admission to hospital for
      the elderly.

PMID- 12497761
TI  - [Two brothers with familial hemophagocytic lymphohistiocytosis, treated by
      transplantation of stem cells from a single unrelated donor].
AB  - In two Turkish brothers familial haemophagocytic lymphohistiocytosis (FHLH) was
      diagnosed at 3 years and 2.5 months, respectively. FHLH is a rare autosomal
      recessive condition with a typical clinical presentation including prolonged
      fever, failure to thrive, irritability and hepatosplenomegaly. Laboratory
      evaluations show cytopenia (at least two out of the three cell lines),
      hypertriglyceridaemia and hypofibrinogenaemia. A pathognomonic sign is
      haemophagocytosis in bone marrow or tissue biopsy. Both patients were treated
      with stem-cell transplants using bone marrow and peripheral blood stem cells,
      respectively, from one unrelated donor. They showed a good haematological
      recovery, with minor complications, and at follow-up after one year were free of
      disease. Immune suppression can induce prolonged remission in FHLH, but cure is
      only achieved after a successful allogeneic stem-cell transplantation. Without
      transplantation, the prognosis is very poor.

PMID- 12497762
TI  - ['Necessity' determined on the basis of disease severity when prioritising health
      care interventions].
AB  - In the Netherlands, the Priorities in Healthcare [Keuzen in de Zorg] Committee
      proposed that the prioritisation of healthcare interventions should in part be
      based on the criterion 'necessity'. However, this criterion has hardly ever been
      used. It was proposed that 'necessity' should be defined in terms of disease
      severity. This concept examines the fraction of expected quality-adjusted life
      years (QALY) that a patient will lose if the condition concerned is not treated.
      The following two possible applications for healthcare policy were studied.
      Firstly, relatively necessary care could be fully reimbursed, whereas less
      necessary care would only be reimbursed in part. Secondly, for relatively
      necessary interventions a lower cost-effectiveness threshold (relatively high
      costs per QALY for necessary care) could be accepted. In these cases the concept
      of disease severity provides a new feasible interpretation of the criterion
      'necessity'.

PMID- 12497763
TI  - [Amyoplasia congenita: a serious congenital abnormality with a relatively
      favorable prognosis].

PMID- 12497764
TI  - [Psychiatric morbidity in adults in the Netherlands: NEMESIS survey. III.
      Psychiatric diseases occur more often in homosexuals than heterosexuals].

PMID- 12497765
TI  - Science based aseptic processing.

PMID- 12497766
TI  - Theoretical analysis of the condensation of hydrogen peroxide gas and water
      vapour as used in surface decontamination.

PMID- 12497767
TI  - Development of the antimicrobial effectiveness test as USP chapter <51>.
AB  - The antimicrobial effectiveness test first appeared as a USP General Chapter in
      the 18th revision, official September 1, 1970. This chapter, at the beginning,
      was designed to evaluate the performance of antimicrobials added to inhibit the
      growth of microorganisms that might be introduced during or subsequent to the
      manufacturing process. As Good Manufacturing Practices (GMPs) became a governing
      principal in pharmaceutical manufacturing, the purpose of the test was refined to
      focus on activity of the preservative system as a protection against inadvertent
      contamination during storage and usage of the product. This article will review
      the history of the antimicrobial test; its function, technique, and the
      background discussions that resulted in the changes from the test that appeared
      in USP XVIII to that of the current USP 25.

PMID- 12497768
TI  - ICH Q7A; 4.40 containment of beta-lactam antibiotics: an industry perspective.
AB  - The ICH Q7A guidance was finalized at the Fifth International Conference on
      Harmonization in San Diego, Nov. 9-11, 2000, and has been implemented in Japan
      since Nov. 2, 2001. However, in ICH Q7A; 4.40, Containment, there is no clear
      stipulation about whether a dedicated or multi-purpose facility should be
      employed in the production of highly sensitizing materials of different types of
      beta-lactam antibiotics, such as cephalosporins and cephems. This study presents
      the threshold levels for the induction of anaphylaxis by beta-lactam antibiotics
      to show that it is possible to use a multi-purpose facility for the production of
      several different types of beta-lactam antibiotics except for penicillins, if
      there are validated cleaning standards based on threshold values.

PMID- 12497769
TI  - Operating precision of steam BIER vessels and the interactive effects of varying
      Z values on the reproducibility of listed D values.

PMID- 12497770
TI  - Extractable/leachable substances from plastic materials used as pharmaceutical
      product containers/devices.
AB  - A review is provided related to the accumulation of organic and inorganic
      leachable substances from DEHP-plasticized PVC, polyolefin and various other
      related pharmaceutical plastic packaging materials. The review considers both the
      identification of such leachables as well as their reported levels in actual and
      simulated pharmaceutical products.

PMID- 12497771
TI  - Pittsburgh Regional Healthcare Initiative puts new spin on improving healthcare
      quality.
AB  - For nearly 4 years, the Pittsburgh Regional Healthcare Initiative (PRHI) has been
      working to improve the way healthcare is delivered in southwestern Pennsylvania
      by combining the voices and resources of hospitals, providers, the business
      community, insurers, health plans, and federal agencies. As one example of
      borrowing from business, the PRHI has created a new learning and management
      system, called Perfecting Patient Care, which is based on the Toyota Production
      System model and is now being used successfully in hospitals.

PMID- 12497772
TI  - Clinical quality, hospital patient safety important to healthcare consumers.
AB  - While consumers still see cost as a top concern in receiving healthcare services,
      clinical quality is rapidly replacing service quality as the next most important
      issue, according to focus group findings in a new VHA report: "Consumers Look at
      Clinical Quality: Beyond Bricks and Mortar."

PMID- 12497773
TI  - [Clinical and diagnostic features of ischemic cardiopathy in women].

PMID- 12497774
TI  - Acute coronary syndromes in women: pathophysiology and therapeutic options.
AB  - Patients presenting with acute coronary syndromes disclose a number of gender
      related differences. Women are more likely than men to have unstable angina and
      less likely to present with myocardial infarction. Women have a better prognosis
      than men among patients with unstable angina. Among patients with myocardial
      infarction without ST-segment elevation, men and women show similar outcomes. In
      contrast, among patients with myocardial infarction and ST-segment elevation,
      women consistently show a worse prognosis than men. This difference is not fully
      explained by age, comorbidities, extent of epicardial artery disease, or baseline
      left ventricular function, and may reflect gender differences in
      pathophysiological, functional and anatomical variables. Moreover,
      revascularization procedures and several anti-ischemic drugs appear underutilized
      in women.

PMID- 12497775
TI  - Risks and benefits of hormone replacement therapy for the prevention of
      cardiovascular disease.
AB  - Study of the circulatory effects of ovarian hormones has become a subject of
      increasing interest with the promise of new treatment approaches for the
      prevention of cardiovascular disease. Work with estrogens is the most extensive
      and does indicate the benefits outweigh the risks albeit we continue to await the
      findings of several large, prospective randomized trials. The addition of
      progestins does appear to be compromising but it is possible that an approach
      will be developed that is cardioprotective without increasing the cancer risk.

PMID- 12497776
TI  - [Strategies for primary and secondary prevention in women].

PMID- 12497777
TI  - [Selection criteria in the treatment of arterial hypertension and recommended
      guidelines].

PMID- 12497778
TI  - [Delayed delivery diuretics: from pharmacology to clinical use].

PMID- 12497779
TI  - [Role of diuretics in the treatment of hypertensive patients at risk].

PMID- 12497780
TI  - Left ventricular hypertrophy regression: the LIVE trial.
AB  - Left ventricular hypertrophy (LVH) is a clinical condition associated with an
      increased risk of vascular events. Several trials have been done to evaluate the
      action of different antihypertensive treatments on the regression of LVH IN
      HYPERTENSIVE PATIENTS. The efficacy of diuretics in the reduction of LVH is
      controversial. The LIVE study (Left Ventricular Hypertrophy Regression:
      Indapamide Versus Enalapril) is a European, prospective, double-blind,
      randomised, controlled trial aimed to compare the efficacy of indapamide 1.5 mg
      daily with that of enalapril 20 mg daily in the reduction of LVH in hypertensive
      patients (systolic blood pressure > 160 and < 210 mmHg) with LVH (left
      ventricular mass index 120 g/m2 in men and > 100 g/m2 in women) after 1 year of
      treatment. The assessment of LVH was done by echocardiography. A blind randomised
      reading of the echo recordings was performed at the end of the study by an
      independent Core Echocardiography Committee with three readers. Preliminary data
      are available from this trial. These data confirm the antihypertensive efficacy
      of indapamide and its efficacy in the reduction of left ventricular mass through
      a progressive action over 1 year.

PMID- 12497781
TI  - [Restenosis: mechanisms].

PMID- 12497782
TI  - [Restenosis: diagnostic criteria].

PMID- 12497783
TI  - [Prevention of restenosis: besides stents, what has the lead?].

PMID- 12497784
TI  - [New horizons in revascularization: neoangiogenesis].

PMID- 12497785
TI  - [New indications for cardioverter-defibrillator implant: heart failure].

PMID- 12497786
TI  - [Current indications for cardioverter-defibrillator implant in patients with
      syncope].

PMID- 12497787
TI  - [Definition and prognosis in unstable angina].

PMID- 12497788
TI  - [Stratification of risk in clinical practice].

PMID- 12497789
TI  - [New strategies in the management of unstable angina/non-Q infarction: clinical
      results of the PURSUIT study].

PMID- 12497790
TI  - [Tridimensional echocardiography].

PMID- 12497791
TI  - [Coronary reserve].

PMID- 12497792
TI  - [New perspectives in echocardiography: myocardial perfusion. What we need to
      know].

PMID- 12497793
TI  - [Assessment of transmural heterogenicity of contractions: new perspectives in
      echocardiography].

PMID- 12497794
TI  - [Cardiac morphology and function].

PMID- 12497795
TI  - [Magnetic resonance in cardiology: myocardial perfusion].

PMID- 12497796
TI  - [Visualization of coronary circulation with magnetic resonance].

PMID- 12497797
TI  - [Myocardial magnetic resonance spectroscopy].

PMID- 12497798
TI  - [Obesity: a time bomb to be defused].

PMID- 12497799
TI  - [Obesity and left ventricular function].

PMID- 12497800
TI  - [Obesity and cardiovascular risk].

PMID- 12497801
TI  - [Therapeutic perspectives in overweight and obesity].

PMID- 12497802
TI  - [An old strategy which comes up again: metabolic therapy of acute myocardial
      infarction].

PMID- 12497803
TI  - [Update on anticoagulant therapy].

PMID- 12497804
TI  - [New third-class drugs].

PMID- 12497805
TI  - [Cardiac sources of embolism].

PMID- 12497806
TI  - [Cryptogenetic stroke].

PMID- 12497807
TI  - [Therapeutic strategies in the treatment of sources of embolism in
      cerebrovascular disease. Pharmacologic treatment].

PMID- 12497808
TI  - [Patent foramen ovale and cryptogenic stroke: role of interventional
      hemodynamics].

PMID- 12497809
TI  - [Acute myocardial infarction: thrombolysis].

PMID- 12497810
TI  - [Acute myocardial infarction: primary angioplasty].

PMID- 12497811
TI  - [Timing of surgical intervention in aortic defects].

PMID- 12497812
TI  - [Timing in surgical interventions for aortic valve disease].

PMID- 12497813
TI  - [Multivessel coronary disease: angioplasty of the culprit lesion or complete
      revascularization].

PMID- 12497814
TI  - [Multivessel coronary disease: complete revascularization].

PMID- 12497815
TI  - [EPA and DHA ethyl esters: potential mechanisms of antischemic action].

PMID- 12497816
TI  - [From large trials and the GISSI Prevenzione study to field secondary
      prevention].

PMID- 12497817
TI  - [Dynamic assessment of the sensitivity of heart baroreflexes control: new
      perspectives].

PMID- 12497818
TI  - [Invasive and non-invasive assessment of baroreflexes: redundant or complementary
      information?].

PMID- 12497819
TI  - [Assessment of sensitivity of heart baroreflexes control in various pathological
      conditions].

PMID- 12497820
TI  - [Spectral analysis of arterial pressure variability, heart rate, and muscular
      sympathetic nerve activity in man].

PMID- 12497821
TI  - The coronary microcirculation in left ventricular hypertrophy.

PMID- 12497822
TI  - [Changes in resistance small arteries in arterial hypertension: clinical
      significance and possibility of pharmacologic remission].

PMID- 12497823
TI  - [Peculiar features of the physiopathology of coronary circulation in hypertensive
      patients: therapeutic implications].

PMID- 12497824
TI  - Unstable angina and non-Q-wave myocardial infarction. Treatment beyond aspirin
      and heparin.

PMID- 12497825
TI  - [Prevalence of heart failure in function of age and relative relevance of current
      clinical trials].

PMID- 12497826
TI  - [Heart failure in the elderly: differences, problems, and uncertainty].

PMID- 12497827
TI  - [Neuroendocrine changes, remodelling, and peripheral changes in heart failure in
      elderly patients].

PMID- 12497828
TI  - [Pharmacologic treatment in elderly patients with heart failure. Which
      precautions?].

PMID- 12497829
TI  - [Hypertensive cardiopathy: a problem that is still important].

PMID- 12497830
TI  - [Vasopeptidase inhibitors: new pharmacologic classes, new therapeutic
      opportunities].

PMID- 12497831
TI  - [Omapatrilat: current data and future perspectives].

PMID- 12497832
TI  - [Autonomic nervous system and arrhythmogenesis].

PMID- 12497833
TI  - [Autonomic reflexes and ventricular tachycardia].

PMID- 12497834
TI  - [Autonomic nervous system and tachyarrhythmia in heart failure].

PMID- 12497835
TI  - [Autonomic nervous system and atrial fibrillation].

PMID- 12497836
TI  - [Does apoptosis participate in heart failure?].

PMID- 12497837
TI  - [Epidemiology and natural history of cardiovascular diseases].

PMID- 12497838
TI  - [Relationship between hypercholesterolemia and coronary disease: Italian data and
      international data].

PMID- 12497839
TI  - [New risk factors related with genetic background].

PMID- 12497840
TI  - [Prevention of cardiovascular diseases. Primary prevention: field intervention].

PMID- 12497841
TI  - [Electrophysiological bases of atrial fibrillation].

PMID- 12497842
TI  - [Paroxysmal atrial fibrillation: epidemiology and clinical relevance].

PMID- 12497843
TI  - [Persistent atrial fibrillation: when to use cardioversion].

PMID- 12497844
TI  - [Pharmacologic treatment of persistent atrial fibrillation].

PMID- 12497845
TI  - [Persistent atrial fibrillation: electric cardioversion].

PMID- 12497846
TI  - [Persistent atrial fibrillation: cardioversion and anticoagulation].

PMID- 12497847
TI  - [Persistent atrial fibrillation: prevention of recurrence].

PMID- 12497848
TI  - [Role of pacing in the prevention of recurrence].

PMID- 12497849
TI  - [Control of ventricular frequency in permanent atrial fibrillation].

PMID- 12497850
TI  - [Prevention of thromboembolism in non-valvular atrial fibrillation].

PMID- 12497851
TI  - [Indications for the use of echo-contrast in venous disease].

PMID- 12497852
TI  - [Angiography with computerized tomography].

PMID- 12497853
TI  - [Current role of phlebography for the diagnosis of deep venous thrombosis].

PMID- 12497854
TI  - [Second-level angiologic diagnosis: current indications.Arteriography].

PMID- 12497855
TI  - [Stenosis of supra-aortic vessels].

PMID- 12497856
TI  - Aortic decoarctation in adults: balloon angioplasty and stenting.

PMID- 12497857
TI  - [Treatment of abdominal aortic aneurysm: traditional or endovascular surgery?].

PMID- 12497858
TI  - [Stenosis of renal arteries].

PMID- 12497859
TI  - [Stenosis of iliac arteries].

PMID- 12497860
TI  - [Clinical trials. When and why: the principle of randomization and double-blind
      method].

PMID- 12497861
TI  - [Significance of reliable data: informatics in the collection of data and
      centralized reading].

PMID- 12497862
TI  - [Interpretation of results of a trial: from a population to the single
      individual].

PMID- 12497863
TI  - [Critical review of published trials].

PMID- 12497864
TI  - [Methodologic rigour and ethics: from the patient to science].

PMID- 12497865
TI  - [Dynamic monitoring of blood pressure for 24 hours. From the research laboratory
      to clinical practice: problems and perspectives].

PMID- 12497866
TI  - [Monitoring of blood pressure for 24 hours: historical, technical, and
      methodological features].

PMID- 12497867
TI  - [Significance and limits of dynamic monitoring of blood pressure in the clinical
      assessment of hypertensive patients].

PMID- 12497868
TI  - [Dynamic monitoring of blood pressure and assessment of antihypertensive drugs].

PMID- 12497869
TI  - [Dynamic monitoring of blood pressure: population studies].

PMID- 12497870
TI  - [Mutations and polymorphisms: clinical significance in cardiology].

PMID- 12497871
TI  - [Genetic polymorphisms for the definition of risk in ischemic cardiopathy].

PMID- 12497872
TI  - [Molecular diagnosis in cardiology].

PMID- 12497873
TI  - [Molecular therapeutic strategies in cardiology].

PMID- 12497874
TI  - [Physician-patient relation in cardiology].

PMID- 12497875
TI  - [The general physician and the field cardiologist: a complementary relationship].

PMID- 12497876
TI  - [Field cardiology and recovery structure: communication and operative synergism].

PMID- 12497877
TI  - [Exploration of the frequency domain in cardiovascular neuroregulation].

PMID- 12497878
TI  - [Standards for commercialization of medications in the European Union].

PMID- 12497879
TI  - [Use of the notes of the Single Commission of Medications].

PMID- 12497880
TI  - The future of antiarrhythmic therapy.

PMID- 12497881
TI  - [Failure resulting from diastolic dysfunction].

PMID- 12497882
TI  - [ACE-inhibitors, AT1 receptor antagonists and diastolic dysfunction].

PMID- 12497883
TI  - [Diastolic heart failure: excess or diminution of compliance?].

PMID- 12497884
TI  - [Beta blockers and calcium antagonists in diastolic dysfunction].

PMID- 12497885
TI  - [Instrumental diagnosis: is carotid angiography always necessary?].

PMID- 12497886
TI  - [Carotid disease: when to apply medical, interventionist, and surgical
      treatment].

PMID- 12497887
TI  - [Surgical problems related to the association of atherosclerosis in other areas].

PMID- 12497888
TI  - [New findings in hypertension treatment: role of angiotensin II antagonists].

PMID- 12497889
TI  - [Dyslipidemia as cardiovascular and cerebrovascular risk factor: epidemiology and
      physiopathology].

PMID- 12497890
TI  - [Treatment of dyslipidemia in specific patient groups].

PMID- 12497891
TI  - [Pharmacologic treatment with statins].

PMID- 12497892
TI  - Inflammation and early events in atherogenesis.

PMID- 12497893
TI  - [Infective agents in the pathogenesis of ischemic cardiopathy].

PMID- 12497894
TI  - [Leukocyte activation in ischemic cardiopathy].

PMID- 12497895
TI  - [Epidemiologic and socioeconomic impact of heart failure].

PMID- 12497896
TI  - [Hospital-field comprehensive care models for the management of the patient with
      failure].

PMID- 12497897
TI  - [Role of heart rehabilitation in failure].

PMID- 12497898
TI  - [Organization of a health education program for failure].

PMID- 12497899
TI  - [Identification of vital myocardium: perfusion study or inotropic reserve
      assessment?].

PMID- 12497900
TI  - [Vitality and inducible ischemia: to which degree do they coincide?].

PMID- 12497901
TI  - [Vital myocardium and post-infarction ventricular remodelling].

PMID- 12497902
TI  - [Vitality and prognosis in infarction patients].

PMID- 12497903
TI  - [History and significance of guidelines in cardiology: the example of arterial
      hypertension].

PMID- 12497904
TI  - [Agonist sports activity and arrhythmia].

PMID- 12497905
TI  - [Update on the treatment with nitrates in ischemic cardiopathy].

PMID- 12497906
TI  - [Neurohormone hypothesis in heart failure: new therapeutic opportunities].

PMID- 12497907
TI  - [Neurohormonal hypothesis and arterial hypertension: therapeutic implications].

PMID- 12497908
TI  - [Neurohormonal hypothesis and sudden death: a logical explanation of unexpected
      data?].

PMID- 12497909
TI  - Dilated cardiomyopathy and muscular dystrophies: which lesson can be learned?

PMID- 12497911
TI  - [Brugada syndrome. Clinical, epidemiologic, and electrophysiologic features].

PMID- 12497910
TI  - [Hypertrophic cardiomyopathy].

PMID- 12497912
TI  - [Progress in molecular genetics of arrhythmogenic cardiomyopathy of the left
      ventricle].

PMID- 12497913
TI  - [Wake-sleep cycle and vegetative regulation].

PMID- 12497914
TI  - [Circadian rhythm in myocardial infarction in relation to the site and the
      different cases of coronary involvement].

PMID- 12497915
TI  - [Circadian rhythm of coronary reserve in ischemic cardiopathy].

PMID- 12497916
TI  - Circadianicity of hemostatic function and coronary vasomotion.
AB  - Acute myocardial infarction, sudden cardiac death and ischemic stroke show a
      circadian periodicity, occurring more frequently in the morning. Because arterial
      thrombosis is common to these disorders, a circadianicity of prothrombotic and
      antithrombotic processes may contribute to explain the 24 h rhythms of these
      acute events. Available data indeed indicate that coronary vasomotor tone,
      platelet aggregability, plasma inhibition of fibrinolysis, coagulant activity and
      blood viscosity are all greater in the morning than at other times of day,
      producting a relative prothrombotic state in the early morning.

PMID- 12497917
TI  - [Surrogate end points in the assessment of benefits of antihypertensive
      treatment].

PMID- 12497918
TI  - [Hypertension and atherosclerosis].

PMID- 12497919
TI  - [Ventricular arrhythmia and hypertension].

PMID- 12497920
TI  - [Arterial hypertension and dementia].

PMID- 12497921
TI  - [Long-QT caused by drugs and torsade de pointes: a genetic basis?].

PMID- 12497922
TI  - [Integrated approach to heart failure: a teaching and medical update model].

PMID- 12497923
TI  - [Heart failure: a neurohormonal disorder?].

PMID- 12497924
TI  - Heart failure: a skeletal muscle disorder?

PMID- 12497925
TI  - [Heart failure: an endothelial disorder?].

PMID- 12497926
TI  - [Diagnostic and prognostic assessment in acute coronary syndromes].

PMID- 12497927
TI  - [Rationale of the cardioprotective effect of diltiazem].

PMID- 12497928
TI  - [Diltiazem in acute coronary syndromes].

PMID- 12497929
TI  - [Myocardial infarction in the elderly. Significance of autonomic markers in the
      early risk stratification].

PMID- 12497930
TI  - [Significance of ambulatory pressure monitoring in the assessment of
      antihypertensive agents].

PMID- 12497931
TI  - Antihypertensive treatment: full 24 hour control and trough to peak ratio.

PMID- 12497932
TI  - [Trough-peak ratio and the smoothness index in the assessment of duration and
      homogeneity of 24-hour antihypertensive effect].

PMID- 12497933
TI  - [Myocardial perfusion: role of contrast echocardiography].

PMID- 12497934
TI  - [Myocardial perfusion: methodology of analysis. The angiographic approach
      revisited].

PMID- 12497935
TI  - [Clinical pharmacology of nebivolol].

PMID- 12497936
TI  - [Therapeutic effects of nebivolol].

PMID- 12497937
TI  - [Hemodynamic properties of nebivolol].

PMID- 12497938
TI  - [Perfusion myocardial scintigraphy after coronary angiography: a way to choose
      from medical, surgical, or intervention therapy].

PMID- 12497939
TI  - [Effects of myocardial revascularization assessed with positron emission
      tomography].

PMID- 12497940
TI  - [Non-fluoroscopic system for the tridimensional electroanatomical heart mapping
      (CARTO)].

PMID- 12497941
TI  - [The non-contact mapping].

PMID- 12497942
TI  - [Transvenous removal of permanent electrocatheters for heart stimulation and
      defibrillation].

PMID- 12497943
TI  - [From the results of large trials to the optimal management of a patient].

PMID- 12497944
TI  - Diabetes: a new challenge in the prevention of coronary heart disease.

PMID- 12497945
TI  - [Present and future of simvastatin: new questions for the third millennium].

PMID- 12497946
TI  - Sudden death in the young and in the athlete: causes, mechanisms and prevention.

PMID- 12497947
TI  - Coronary stenting: current state of the art.

PMID- 12497948
TI  - [Angiotensin II receptor antagonists in arterial hypertension: new clinical
      evidence with candesartan].

PMID- 12497949
TI  - [Atrial tachycardia and flutter].

PMID- 12497950
TI  - [Nodal paroxysmal tachycardia].

PMID- 12497951
TI  - [Mahaim fiber tachycardia and re-entry tachycardia through decremental
      atrioventricular accessory pathways with anterograde unidirectional block].

PMID- 12497952
TI  - [Coronary stents: elective use].

PMID- 12497953
TI  - [Coronary stents in emergencies].

PMID- 12497954
TI  - [Is there an ideal stent for each type of coronary lesion?].

PMID- 12497955
TI  - [Radioactive stents].

PMID- 12497956
TI  - [Genetics as a guide for antihypertensive therapy: future perspectives].

PMID- 12497957
TI  - [New therapeutic strategies in heart failure. Pharmacologic therapy].

PMID- 12497958
TI  - [Electromechanical re-synchronization with sequential heart stimulation as a new
      non-pharmacologic treatment of advanced heart failure. Physiopathologic features
      and clinical results].

PMID- 12497959
TI  - [New therapeutic strategies in heart failure. Which patients need defibrillation
      backup?].

PMID- 12497960
TI  - An ethicist's commentary on the case of the client requesting anesthesia
      medication.

PMID- 12497961
TI  - CVMA Task Force on "education, licensing, and the expanding scope of veterinary
      practice".

PMID- 12497962
TI  - Time to critical overcrowding of Manitoba swine barns in the event of restriction
      on animal movement.
AB  - Canada maintains a stamping-out policy for control of foreign animal disease.
      Integral to stamping out, there are obligatory animal movement restrictions that,
      over time, can result in severe animal welfare problems. The purpose of this
      study was to estimate the time to critical overcrowding in a sample of Manitoba
      swine farms, if they were placed under movement restriction. Time to critical
      overcrowding in both static and dynamic populations was estimated by modeling
      swine growth and projecting anticipated on-farm stocking density through time and
      comparing it with a standard maximal stocking density. The time to critical
      overcrowding of 15 isowean piglet production units was 0.66 +/- 0.88 weeks. On
      average, 7 isolated nursery facilities reached critical overcrowding in 52 +/- 14
      days and 5 farrow-to-finish operations reached critical overcrowding in 43 +/- 18
      days. Animal welfare concerns should be included in contingency plans to control
      foreign animal disease.

PMID- 12497963
TI  - Coinfection with bovine viral diarrhea virus and Mycoplasma bovis in feedlot
      cattle with chronic pneumonia.
AB  - Chronic, antibiotic-resistant pneumonia, sometimes with concurrent polyarthritis,
      occurs in feedlot cattle in western Canada. The prevalence of Mycoplasma bovis,
      bovine viral diarrhea virus, and Haemophilus somnus was determined by using
      immunohistochemical staining of lung and heart tissue from 2 groups of animals
      with this history. Mycoplasma bovis antigen was present in 44/48 cases submitted
      between 1995 and 1998 (retrospective group) and 15/16 of cases from 1999
      (prospective group), and was associated with pulmonary necrosis. Bovine viral
      diarrhea virus antigen was present in association with microscopic vascular
      lesions in 31/48 retrospective and 9/16 of prospective cases. Types Ib and II
      bovine viral diarrhea virus were isolated from 4/16 prospective cases.
      Haemophilus somnus antigen was present in heart, lung, or both of 15/48
      retrospective and 8/16 prospective cases. The results suggest that there may be
      synergism between bovine viral diarrhea virus and M. bovis in this pneumonia with
      arthritis syndrome.

PMID- 12497964
TI  - Comparison of lidocaine and compression for velvet antler analgesia in wapiti.
AB  - This research compared ring block lidocaine anesthesia (L) and compression (C)
      for velvet antler removal in elk. Thirty-two wapiti were given 1 mg/kg body
      weight of zuclopenthixol acetate. The next day, they were restrained in a
      hydraulic chute and given either a compression device or a lidocaine ring block
      on the antler pedicle. Behavioral and physiological responses to treatment
      application and antler removal were recorded, and blood was collected for
      cortisol analysis. During application of L and C, increases in mean heart rate
      and systolic arterial blood pressure were greater in the C treatment group (P <
      0.05, and P = 0.05, respectively). When antler was removed, more behavioral
      responses occurred in the C treatment group (P = 0.02) and its median behavior
      score was higher (P = 0.03). Mean heart rates increased for both treatment groups
      when antlers were removed (P < 0.01). It was concluded that application of C may
      be painful, and that C was not as effective as L for analgesia for velvet antler
      removal.

PMID- 12497965
TI  - Angiostrongylus vasorum infection in 2 dogs from Newfoundland.
AB  - Described are the first antemortem diagnosis made via fecal examination using the
      Baermann technique and the first postmortem recovery of endemic Angiostrongylus
      vasorum in dogs from North America, specifically the Avalon peninsula of
      Newfoundland. In one dog, A. vasorum was recovered and identified at postmortem;
      gross and histologic lesions are described.

PMID- 12497966
TI  - Chronic wasting disease in a Rocky Mountain elk.
AB  - A 24-month-old Rocky Mountain elk was presented because of suspected chronic
      wasting disease (CWD). The animal was emaciated, had retained its winter hair,
      and had abnormal behavior patterns suggestive of CWD, including bruxism,
      ptyalism, and diminished flight zone size. Immunohistochemical analysis of the
      brain confirmed the diagnosis of CWD.

PMID- 12497967
TI  - Craniomandibular osteopathy in a bullmastiff.
AB  - A 6-month-old bullmastiff was presented with bilateral painful swellings of the
      mandible. Craniomandibular osteopathy was diagnosed based on skull radiographs
      and histological findings from bone biopsies. Treatment consisted of meloxicam to
      alleviate the pain. Three months later, the dog was pain free without medication
      or palpable change in the mandible.

PMID- 12497968
TI  - Screening for chronic wasting disease in caribou in northern Quebec.

PMID- 12497969
TI  - Diagnostic ophthalmology.

PMID- 12497970
TI  - Re-treatment of mosquito nets with insecticide.

PMID- 12497971
TI  - Wash resistance of insecticide-treated materials.
AB  - The effectiveness of insecticide-treated materials (ITMs) for malaria control is
      reduced by washing them. This research in Colombia and Bolivia investigated the
      resistance of different insecticide formulations and, in particular, a
      commercially available impregnated bednet (PermaNet) which provides chemical
      protection for the insecticide. The fabrics studied were all polyester; the
      pyrethroids used for impregnation were deltamethrin (tablet and suspension
      concentrate both at 25 mg/m2 target dose), lambdacyhalothrin (capsule suspension
      at 15 mg/m2; laboratory study only), alphacypermethrin (suspension concentrate at
      40 mg/m2) and, in the case of PermaNet, deltamethrin (55 mg/m2). The indicator of
      wash resistance was Anopheles spp. mortality (using the bioassay cone method)
      before and after different numbers and intensities of washing. When the fabrics
      were washed under controlled conditions, gently with water and a bar of soap, the
      wash resistance of all formulations was good (100% Anopheles mortality after 3
      washes). However, when the impregnated nets were soaked for 30-60 min and washed
      with soap powder and tap water by local women in the usual way, the mortality
      after 4 washes declined considerably (43.5% and 41.3% for deltamethrin tablets
      and liquid respectively when washing every second day). Alphacypermethrin showed
      slightly better results after 3 washes every 7th day compared to deltamethrin
      tablets (63.8% and 43.3% mortality, respectively). The wash resistance offered by
      PermaNet was much better and longer lasting: Anopheles mortality after 4 washes
      was 92.6%, after 10 washes 83.7% and after 20 washes 87.1%. The limitations of
      commercially available wash-resistant nets are, however, their limited
      accessibility and the difficulty of replacing all existing bednets with a new
      product.

PMID- 12497972
TI  - Epidemiology of malaria from East Timor among Australian Defence Force personnel.

PMID- 12497973
TI  - Trypanosoma cruzi isoenzyme variability in Ecuador: first observation of zymodeme
      III genotypes in chronic chagasic patients.
AB  - We have analysed by multilocus enzyme electrophoresis (MLEE) at 21 genetic loci
      10 Trypanosoma cruzi stocks isolated from chronic chagasic patients and 3 stocks
      isolated from Triatoma dimidiata collected in human habitats from the coastal
      part of Ecuador (all stocks isolated in August-December 1998). Isoenzyme profiles
      were compared to those of 4 laboratory-cloned stocks representing the major
      phylogenetic subdivisions of T. cruzi. This parasite's genetic variability in
      Ecuador proved to be considerable, even in this limited sample, since all main
      isoenzyme genotypes were recorded. Four stocks from patients were identical at
      all loci to the reference stock MNcl2 ('major clonet #39'; T. cruzi II) isolated
      in Chile. The 3 stocks isolated from T. dimidiata were closely related to the
      formerly described zymodeme I (T. cruzi I). Finally, 3 stocks from chronic
      chagasic patients (one with an asymptomatic form, 2 with a cardiac-digestive
      form) were closely related to the formerly described zymodeme III (presently not
      classified in either T. cruzi I or T. cruzi II). This is the first observation of
      this category of T. cruzi genotypes in chronic chagasic patients. In the past it
      was recorded only in acute patients, wild mammals and wild triatomine bugs. The
      epidemiological implications of these results are discussed.

PMID- 12497974
TI  - Combined eco-epidemiological and molecular biology approaches to assess
      Echinococcus granulosus transmission to humans in Mauritania: occurrence of the
      'camel' strain and human cystic echinococcosis.
AB  - Mauritania lies between West-Central Africa where human cystic echinococcosis
      (CE) is considered extremely rare and West Maghreb where CE accounts for a real
      public health problem. Until 1992, Mauritania was considered as human CE-free
      even through CE seemed well known in livestock. In 1992, the introduction of
      ultrasonography led to the diagnosis of the first human CE cases. In 1997, a
      veterinary study revealed that dogs living around Nouakchott were commonly
      infected by Echinococcus granulosus. To assess E. granulosus transmission and to
      identify the most relevant animal reservoir responsible for human CE emerging in
      Mauritania, a simultaneous eco-epidemiological and molecular biology approach was
      performed. The fieldwork included sample collection and investigation of
      relationship between intermediate hosts, definitive hosts and humans. Typing of
      E. granulosus strains was performed using comparison of polymerase chain reaction
      (PCR)-amplified DNA sequences with one nuclear (BG 1/3) and 2 mitochondrial (COI,
      NDI) targets. Results show that the 'camel' strain is actually infectious to
      humans and circulates between intermediate hosts including camels and cattle. It
      is suggested that preventive measures at slaughtering places could reduce human
      contamination.

PMID- 12497975
TI  - The seasonal pattern of dengue in endemic areas: mathematical models of
      mechanisms.
AB  - In dengue-endemic areas such as Thailand, there is clear seasonality in the
      number of reported cases of dengue virus disease. However, the roles of different
      entomological and biological variables in determining this pattern have not been
      ascertained. To investigate this, seasonally-varying parameters were introduced
      in a step-wise fashion into a mathematical model of the transmission dynamics of
      dengue viruses. The predicted prevalence of infection was then compared to
      observed seasonal patterns of disease. The strongest influences on the pattern of
      infection and its seasonal variation were duration of infectiousness of the host,
      vector mortality, and biting rate. However, seasonally-varying parameters such as
      the latent period of infection in the vector had to be incorporated into the
      model to generate the correct timing of peak infection prevalence. A few limiting
      variables usually control the prevalence of an infectious disease because small
      changes in their values can carry the infection beyond the threshold at which its
      basic reproductive number is one. It was changes in such parameters (vector
      biting and mortality rate) which caused seasonal prevalence, but the timing of
      peak prevalence was a result of time delays within the system.

PMID- 12497976
TI  - First documented outbreak of hepatitis E virus transmission in Java, Indonesia.
AB  - A suspected hepatitis outbreak occurred in Bondowoso District, East Java
      Province, Indonesia, in March-May 1998. An investigation was initiated in April
      1998, involving a retrospective review of hospital records, a community-based
      cross-sectional study, and a health service-based case detection and household
      follow-up. Sera and epidemiological information were collected from 962
      individuals: 235 from 3 outbreak-affected communities along the same rural
      stretch of river, 101 from community controls living distant from the river, 151
      cases detected in health centres, 141 family members of the cases, and 334
      subjects from neighbouring families. The prevalence of acute hepatitis E virus
      (HEV), based on anti-HEV IgM, total antibody (Ig) to HEV and polymerase chain
      reaction (PCR), was significantly (P < 0.00001) higher (52.4%) among the outbreak
      communities than among the community controls (3%). The background prevalence of
      HEV, based on anti-HEV IgG, was also significantly (P < 0.00001) higher (47%)
      among the outbreak communities than among the community controls (3%). None of
      the 476 sera screened for anti-HAV (hepatitis A virus) IgM was positive. These
      results indicate that HEV was the aetiological agent responsible for the
      outbreak. The overall attack rate (AR) for the 3 outbreak-affected communities
      surveyed was 19%, with AR determined on the basis of clinically recognized, acute
      jaundice illness. The usage of river water as primary source for bathing, human
      waste disposal, and drinking purposes differed significantly (P < 0.00001)
      between the communities in outbreak areas and those in non-outbreak areas. There
      is no significant influence attributed to 'boiling water' on acute HEV. No
      climatic influences (flooding or drought) predisposed this instance of epidemic
      HEV transmission. This outbreak represents the first documented evidence of
      epidemic HEV transmission in Java, Indonesia.

PMID- 12497977
TI  - Surveillance and screening of American cutaneous leishmaniasis by Colombian
      primary health care workers using a clinical prediction rule.
AB  - Confirmed cases of American cutaneous leishmaniasis (ACL) and other
      dermatological diseases were evaluated in Colombia with a clinical prediction
      rule independently by 3 types of evaluators: community health volunteer (CHV),
      practical nurse (PN) and programme physician (PP). The adapted prediction rule
      included 6 variables based upon clinical-historical information. The screening
      instrument was a rotating tower of coloured squares, one colour for each
      variable. A score ranging from 0 to 7, and a cutoff point of > or = 4 was
      selected for ACL classification (sensitivity 94.3%, specificity 53.3% and
      efficiency 80.3%). Disease classification, total score, and variable-specific
      score obtained by CHVs and PNs were compared to those obtained by a PP. The
      impact on case detection in the study area was assessed. Both types of primary
      health worker had a high agreement with the PP (sensitivity) on the
      classification of patients with ACL by score, CHV (92.3%) and PN (93.3%). Case
      detection of ACL increased 3-fold over that observed one year earlier. This
      screening instrument and prediction rule, when incorporated into a community
      surveillance programme for ACL, can facilitate greater case detection and
      appropriate referral for more-specific diagnostic procedures.

PMID- 12497978
TI  - Glucose and lactate turnover in adults with falciparum malaria: effect of
      complications and antimalarial therapy.
AB  - Hypoglycaemia and lactic acidosis are potentially life-threatening, poorly
      understood sequelae of Plasmodium falciparum infections. We investigated
      relationships between clinical status, treatment, and glucose and lactate
      kinetics during management of falciparum malaria in 14 Vietnamese adults. Nine
      had severe malaria, of whom 4 were administered quinine (Group 1a) and 5
      artesunate (Group 1b). Five uncomplicated cases received artesunate (Group 2).
      Glucose and lactate turnover were studied on 3 occasions: (i) immediately after
      initial antimalarial treatment, (ii) at parasite clearance a median of 3 days
      later, and (iii) at discharge from hospital a median of 9 days post-admission.
      Steady-state glucose and lactate kinetics were derived from plasma isotopic
      enrichment during a primed-continuous infusion of D-[6,6-D2]glucose and a
      parallel infusion of L-[1-13C]lactate. Group 1a patients had the lowest plasma
      glucose concentrations in the admission study (median [range] 3.9 [3.6-5.1] vs
      6.3 [4.9-7.1] and 4.5 [4.3-5.5] mmol/L in Groups 1b and 2 respectively; P < 0.05
      vs Group 1b), but glucose production rates and serum insulin concentrations that
      were similar to those in the other groups (P > 0.17). This was also the case at
      parasite clearance and suggested an inappropriate beta cell response. Group 1a
      patients had the highest admission lactate production (60 [36-77] vs 26 [21-47]
      and 22 [4-31] mumol/kg.min in Group 1b and 2 respectively; P < 0.05 vs Group 2).
      Amongst the 9 severe cases, there was an inverse association between plasma
      glucose and lactate production at admission and parasite clearance (P < 0.05),
      but no correlation between admission lactate production and serum bicarbonate (P
      = 0.73). The present data confirm previous studies showing that quinine depresses
      plasma glucose through stimulation of insulin secretion. It is hypothesized that
      the low plasma glucose activates Na+,K(+)-ATPase through increased plasma
      catecholamine concentrations, leading to accelerated glycolysis and increased
      lactate production in well-oxygenated tissues. In some severely ill patients with
      falciparum malaria, a raised plasma lactate on its own may, therefore, be an
      unreliable index of a developing acidosis.

PMID- 12497979
TI  - Chloroquine resistance of Plasmodium falciparum is associated with severity of
      disease in Nigerian children.
AB  - Chloroquine resistance of Plasmodium falciparum in vitro was significantly higher
      in isolates from patients with severe malaria than those with uncomplicated
      disease. This association may be due to either progression of uncomplicated to
      severe disease following chloroquine failure or increased virulence of
      chloroquine-resistant parasites. The implication of this for antimalarial
      treatment policy is discussed.

PMID- 12497980
TI  - Trypanosoma brucei gambiense African trypanosomiasis: differences between men and
      women in severity of disease and response to treatment.
AB  - To compare the characteristics of women and men with Trypanosoma brucei gambiense
      trypanosomiasis, all 3231 cases treated in Nioki hospital, Democratic Republic of
      Congo, from 1982 to 2000 were reviewed for demographic information, date and mode
      of diagnosis, pre-treatment cerebrospinal fluid (CSF) examination, treatment
      given and its adverse effects, and whether a diagnosis of relapse was made during
      post-treatment follow-up. Women had a higher apparent incidence of Gambian
      trypanosomiasis than men (1768 cases in females, 1463 in males), due to selective
      migration of males out of endemic foci and potentially to a higher exposure among
      females. Women presented with a less-advanced disease than men: 27% (384/1431) of
      women had CSF trypanosomes and 72% (1024/1431) had an abnormal CSF white cell
      count, while corresponding figures in men were 39% (431/1115) and 82% (910/1115)
      (P < 0.001 for both comparisons), presumably because of differences in health
      seeking behaviour. Men (61/718, 8.5%) were more likely to relapse after
      melarsoprol treatment than women (41/857, 4.8%) (P = 0.004), even after
      adjustment for other independent risk factors in multivariate analysis. The cause
      of this higher risk of treatment failure among men treated with melarsoprol
      remains unclear.

PMID- 12497981
TI  - Portopulmonary hypertension syndrome in schistosomiasis mansoni.
AB  - Portopulmonary hypertension syndrome (PPHS) is a complication of portal
      hypertension where the substrate is micro-vessel lesions which are indicative of
      plexogenic arteriopathy. PPHS has not been linked to pulmonary schistosomiasis.
      We report, to the best of our knowledge for the first time, a case of PPHS
      associated with schistosomiasis mansoni.

PMID- 12497982
TI  - Impact of resistance to anti-tuberculosis drugs on treatment outcome using World
      Health Organization standard regimens.
AB  - We compared treatment outcome in 410 patients with drug-susceptible tuberculosis
      (DS-TB) and 150 patients with drug-resistant tuberculosis (DR-TB) among 560 adult
      patients (> or = 15 years old) notified with smear-positive pulmonary
      tuberculosis between July 1997 and June 1998 in the West Province of Cameroon and
      treated with World Health Organization (WHO) standard regimens under field
      conditions. Information on treatment outcome was collected for all smear-positive
      TB patients having a positive culture with drug susceptibility tests performed
      for isoniazid, rifampicin, ethambutol and streptomycin. Treatment outcome was
      recorded as cured, completed treatment, failed, defaulted, died or transferred
      out, 332 of the 410 patients (81%) with DS-TB were cured, compared to 109/150
      (72.7%) patients with DR-TB (odds ratio [OR] = 0.62, 95% confidence interval [CI]
      0.40-0.99). Seven patients (1.7%) failed treatment in the DS-TB group vs. 9
      (6.0%) in the DR-TB group (OR = 3.67, 95% CI 1.23-11.18). No significant
      difference was found in rates of death, default or transfer. Sputum smear
      conversion at the end of the intensive treatment phase was observed in 78.8% of
      the cases, drug resistance having no effect on the conversion rate. After
      adjusting for age, sex and resistance, the death rate was higher in patients also
      infected with human immunodeficiency virus (HIV). In TB cases with multidrug
      resistance, standard regimens result in unacceptably high failure rates (26.1%).
      For all other drug-resistant forms of TB, rifampicin-based short-course
      chemotherapy gave satisfactory results. The death toll in the West Province seems
      due to HIV co-infection rather than to TB alone. To prevent development of drug
      resistance, the proportion of defaulters must be decreased and prevention and
      control strategies endorsed by the WHO and the International Union Against
      Tuberculosis and Lung Disease must be implemented nation-wide.

PMID- 12497983
TI  - Higher gametocyte prevalence following failure of treatment of Plasmodium
      falciparum malaria with sulfadoxine-pyrimethamine and the combination of
      chloroquine plus sulfadoxine-pyrimethamine: implications for progression of anti
      folate resistance.
AB  - Chloroquine (CQ) treatment of CQ-resistant Plasmodium falciparum is associated
      with a significantly higher prevalence of post-treatment gametocytaemia which has
      been linked to the preferential transmission of CQ-resistant parasites. It is not
      known whether treatment failure (TF) with sulfadoxine-pyrimethamine (SP) is
      associated with the same higher prevalence of gametocytaemia as that seen with CQ
      TF. Using 1997 WHO in-vivo drug efficacy protocols for malaria, we therefore
      compared (in a study in 1999) the frequency of gametocytaemia in those with TF to
      the frequency seen in those with an adequate clinical and parasitological
      response (ACPR) following treatment with one of 3 regimens in Papua, Indonesia:
      SP monotherapy (n = 87; TF 20.7%), CQ monotherapy (n = 48; TF 83.3%), and the
      combination of CQ plus SP (n = 34; TF 38.2%). Following SP, day 7 prevalence was
      significantly higher in those with TF (67%) than with ACPR (38%, P = 0.03).
      Following combination treatment with CQ + SP, the day 14 gametocyte prevalence
      was significantly higher in those with TF (100% vs 38%, P = 0.016). The higher
      prevalence of SP TF-associated gametocytaemia may contribute to increased
      transmission of antifolate-resistant strains, and further cautions against the
      use of SP as monotherapy. Adding SP to CQ, after significant resistance has
      emerged to both drugs, may not prevent enhanced transmission of dual-resistant
      strains and progression of anti-folate resistance.

PMID- 12497984
TI  - Five-year impact of repeated praziquantel treatment on subclinical morbidity due
      to Schistosoma japonicum in China.
AB  - We report the 5-year impact (1996-2001) of repeated praziquantel chemotherapy on
      subclinical morbidity related to Schistosoma japonicum infection. We repeated
      stool examinations and hepatosplenic ultrasonography in a cohort of 120
      individuals living on an island with endemic infection in Dongting Lake, China.
      Prevalence of schistosome infection fell by 43% and intensity (geometric mean
      eggs per gram) declined by 80% over the 5 years. However, transmission persisted
      at a dangerously high rate of 13% per year for re-infection or new infection in
      the cohort. The prevalence of left-lobe enlargement and dilated portal vein fell
      significantly (P < 0.01) to about half initial levels although a few patients
      progressed during the study period. At study endpoint, infection was nearly twice
      as common if the portal vein was dilated (23% versus 13%, respectively), but this
      association was not statistically significant (P > 0.05). However, endpoint
      infection was even more strongly associated with left-lobe enlargement (57%
      versus 15%, P < 0.01). The proportions of subjects with improved parenchymal and
      periportal fibrosis were much higher than the proportions of subjects that
      progressed (P < 0.05). Reduction of prevalence and intensity of infection, and
      improvement of subclinical morbidity, were benefits of repeated treatments.
      Further research is needed to understand why some patients developed fibrosis
      despite substantial reductions in egg counts and to evaluate the functional
      importance of residual subclinical morbidity after chemotherapy-based control in
      the lake and marshland area of China.

PMID- 12497985
TI  - Praziquantel efficacy against schistosomiasis mansoni in schoolchildren in north
      west Ethiopia.
AB  - The efficacy of praziquantel against schistosomiasis mansoni has been measured in
      10-14 years old schoolchildren in a highly endemic area of north-west Ethiopia.
      The egg reduction rate was 97% and the cure rate was 94%, as assessed by a single
      Kato smear. No evidence for praziquantel resistance was detected.

PMID- 12497986
TI  - Lymphatic filariasis-specific immune responses in relation to lymphoedema grade
      and infection status. I. Cellular responses.
AB  - The filariasis-specific cellular responsiveness was assessed in 109 adult
      individuals from a Wuchereria bancrofti-endemic area in north-east Tanzania.
      There were 9 study groups. Five groups of individuals were negative for
      microfilariae (mf) and specific circulating filarial antigen (CFA) and had leg
      lymphoedema of varying severity ranging from early to more advanced grades
      (pathology groups 1-5). Another group comprised individuals with mixed grades of
      lymphoedema and positive for mf and/or CFA (mixed pathology group). Three
      asymptomatic groups consisted of individuals without leg pathology but with
      different infection status: (i) CFA- and mf-negative individuals, (ii) CFA
      positive but mf-negative individuals, and (iii) CFA- and mf-positive individuals.
      Peripheral blood mononuclear cells were collected and proliferative
      responsiveness and secretion of interleukin (IL)-4, IL-10 and gamma interferon
      (IFN gamma) were measured upon stimulation with a Brugia pahangi antigen. No
      distinct differences in responses were observed between the 5 uninfected
      pathology groups. Instead, responses were associated with infection status, with
      generally higher proliferative activity and higher levels of IL-4 and IFN gamma
      in uninfected as compared to infected individuals. High levels of IL-10 were
      observed in asymptomatic individuals without infection and in asymptomatic CFA
      positive but mf-negative individuals. Asymptomatic individuals with mf had
      relatively low IL-10 levels. Groups presenting with chronic pathology generally
      had low levels of IL-10 independently of infection status. The findings thus give
      no immediate indication that the measured immunological parameters are related to
      progression of leg pathology. However, alternative interpretations are presented
      which suggest a possible role of immunological reactions in development of
      pathology in lymphatic filariasis.

PMID- 12497987
TI  - Lymphatic filariasis-specific immune responses in relation to lymphoedema grade
      and infection status. II. Humoral responses.
AB  - The filarial-specific humoral responses (IgG1, IgG2, IgG3, IgG4 and IgE) to a
      Brugia pahangi antigen was assessed in 9 groups of adult individuals from a
      Wuchereria bancrofti-endemic area in north-east Tanzania. In 5 of the groups,
      individuals were negative for microfilariae (mf) and circulating filarial antigen
      (CFA) and had leg lymphoedema of varying severity ranging from early to more
      advanced grades. A 6th group had mixed grades of lymphoedema and were actively
      infected with mf and/or CFA. Three groups of asymptomatic individuals with
      different infection status (mf+CFA+; mf-CFA+; mf-CFA-) were also included. No
      differences in the antibody levels were observed between the 5 uninfected
      pathology groups. However, groups with advanced lymphoedema had a significantly
      higher level of IgG3 as compared to groups with early lymphoedema. A decline in
      the IgG4/IgE ratios were observed when moving from groups with early to groups
      with more advanced lymphoedema, which could indicate that increasing levels of
      IgE relatively to IgG4 are associated with progression of pathology. When all
      study groups were compared, higher IgG4/IgE ratios were observed in infected
      groups than in uninfected groups. This could suggest that high levels of IgG4
      relative to IgE protect the parasite, whereas the opposite may play a role in
      parasite killing. When relating IgG4/IgE ratios to levels of gamma interferon
      (IFN gamma), a clear inverse relationship was observed. Thus, high levels of IFN
      gamma were found in groups with low IgG4/IgE ratios (uninfected groups) and low
      levels of IFN gamma were found in groups with high IgG4/IgE ratios (infected
      groups). The relationship between cellular (IFN gamma) and humoral (IgG4/IgE
      ratios) responses and their possible role in parasite protection and killing, and
      in development of early lymphoedema, are discussed.

PMID- 12497988
TI  - [The general theory of pathophysiological mechanisms of neurological and
      psychopathological syndromes].
AB  - Besides structural and functional deficits, central nervous system (CNS) damage
      causes another effect in the form of novel pathological integrations consisting
      of CNS primarily and secondarily changed structures. At the neuronal level, the
      integration presents as aggregation of hyperactive uncontrollable neurons, which
      produces enhanced uncontrolled impulse flow and acts as a generator of
      pathologically enhanced excitation, network type. At the system interrelation
      level, the integration is represented by a new pathodynamic organization
      including damaged CNS regions, which constitutes a pathological system (PS). The
      hyperactive CNS structure plays a role of a pathological determinant promoting PS
      formation may determine a type of PS activity. A clinical manifestation of PS
      activity is a corresponding neurological or psychopathological syndrome.

PMID- 12497989
TI  - [Hypertensive angioencephalopathies].
AB  - The results of clinical and physiological study of 2000 patients, aged 20-60
      years, suffering from hypertensive encephalopathy with differential evaluation of
      varying cerebrovascular pathology types (according to RAMS Neurology Institute
      classification) and stages of their development were summarized. The complex of
      methods used comprised psychological personality questionnaires,
      neuropsychological methods, computed tomography, rheoencephalography, ultrasonic
      diagnosis, etc. The data was computer processed. The main diagnostic and
      prognostic criteria for chronic hypertensive angioencephalopathies on early
      stages of arterial hypertension and the principles of their prevention are
      outlined.

PMID- 12497990
TI  - [Central nervous system damage in inflammatory demyelinating polyneuropathies].
AB  - The results of subclinical brain damage study of 20 patients with inflammatory
      demyelinating polyneuropathy, aged 46.5 +/- 3.7 years, are presented. Eleven
      patients were diagnosed to have Guillain--Barre syndrome and 9--chronic
      inflammatory demyelinating polyneuropathy. No clinical systems for central
      nervous system damage were found. Magnetic resonance tomography defected
      demyelination foci in periventricular and sub-cortical brain regions in 35% of
      the patients and diffuse atrophic process--in 55%. Registration of brainstem
      acoustic-evoked potentials showed bilateral latency increase and a change of a
      signal shape in 60% of the patients. Possible mechanisms of combined damage of
      central and peripheral nervous system in this pathology are discussed.

PMID- 12497991
TI  - [Clinical heterogeneity of X-linked adrenoleukodystrophy ].
AB  - X-linked adrenoleukodystrophy (X-ALD) is a relatively common world spread disease
      characterized by significant clinical heterogeneity. Clinico-biochemical
      examination in the Medico-genetic research center identified, 20 X-ALD cases in
      17 families over 5 years. Prevalence of children (60%) and adolescence (25%)
      cerebral forms is explained, in part, by patients referring for medical-genetic
      counseling. Adrenomyeloneuropathy was diagnosed in one patient. In two healthy
      siblings presymptomatic stage was found. A main X-ALD biochemical marker is an
      increase of very long chain fatty acids (VLCFA) level, which does not depend on
      clinical form of the disease. Most interesting appeared to be a family including
      5 patients in 3 generations with intrafamilial combination of childhood and
      adolescence cerebral forms, and atypically mild disease course in proband.
      Regarding symptoms of childhood and adolescence cerebral forms, attention has
      been drawn to 3 patients with tics, which mask organic nature of the disease on
      its initial stage. X-ALD is so far incurable, but its timely diagnosis provides
      an adequate medico-genetic help on the base of modern prenatal diagnosis.

PMID- 12497992
TI  - [Clinical peculiarities of the first depressive episodes in adolescents].
AB  - Seventy-three adolescents, aged 10-15 years, have been examined. According to
      analysis of development and psychopathological structure of depressive state and
      personality changes as well as of the features of premanifesting and initial
      stages, nosology of the disorders studied has been established. First depressive
      episodes were observed in 26 patients with attack-like and slow-progredient
      schizophrenia (ICD-10 F20; F21), and in 29 patients with affective disorder (F32;
      F33). Three types of first depressive episode-melancholic, anxious, dysphoriac-
      were determined. In a group with indefinite diagnosis (18 patients),
      differentiation of a state was conducted between schizophrenia, atypical puberty
      and affective disorder in accentuated personality.

PMID- 12497993
TI  - [Intermittent hypoxia in the treatment of dyscirculatory encephalopathy].
AB  - An influence of intermittent hypoxia (IH) on antioxidant enzymes activity was
      investigated in 42 patients, aged 48.2 +/- 1.8 years, with 1-2-nd stage of
      dyscirculatory encephalopathy (DE) in the presence of I-II stage of arterial
      hypertension (AH). Patients with arterial pressure below 145/85 mmHg receiving
      basic antihypertensive drugs treatment were included in the study. Before IH, the
      patients showed increased total oxidant activity (TOA) as well as concentration
      of thiobarbituric acid reactive substances (TBRS) in blood plasma and reduced
      activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GP) in erythrocytes comparing to control group (14 healthy subjects). In 27
      patients, it was combined with increased peak systolic and peak diastolic blood
      flow rate in middle cerebral artery according to Doppler examination. After 10
      days hypoxia training (60 min daily atmospheric air breathing alternated with 9
      10 V% O2 hypoxic mixture breathing), TOA and TBRS were decreased by 39% and 25%
      respectively, whereas enzymes activity was increased as follows: SOD--by 29%; CAT
      -by 18%; GP--by 38%. The treatment resulted in reduction of peak systolic and
      peak diastolic blood flow rate in the meddle cerebral artery, decrease of
      frequency of headache episodes and in improvement of nighttime sleep and short
      term memory. The results demonstrate a possibility for correction of oxidative
      homeostasis disturbances in patients with DE on the background of AH and can be
      beneficial for DE prevention and treatment.

PMID- 12497994
TI  - [Neurovisualization in diagnosis of mesial temporal sclerosis in children].
AB  - We present specific magnetic resonance characteristics of mesial temporal
      sclerosis (MTS) represented by hypoxic-ischemic, dysplastic and mixed clinical
      variants. Temporal size decrease, irregular grey-white differentiation and
      ipsilateral dilatation of inferior horn of lateral ventricle were identified as
      specific MTS markers.

PMID- 12497995
TI  - [Clinico-immunological comparisons in evaluation of interferon system functioning
      in patients with multiple sclerosis].
AB  - In search for rational approach for immunotherapy individualization in patients
      with multiple sclerosis (MS) assigned to interferon (IFN) treatment, an
      evaluation of IFN-alpha and IFN-gamma production by peripheral blood leucocytes
      (PBL) under standard induction and exogenous IFN priming in comparison with
      clinical characteristics was made. Fifteen patients with MS (6 males and 9
      females, aged 25-58 years) with verified diagnosis of MS were examined. IFN
      production priming allowed to obtain characteristics of IFN system deficiency,
      which could not be detected by standard induction methods. Correlation between
      induced and primed PBL. IFN-gamma production and MS severity, duration and course
      was found. Patients with no PBL blood cells dissociate response to IFN-alpha and
      IFN-gamma exhibited less neurological deficit than those with associations in
      response. A use of blood cell sensitivity to exogenous IFN in individualization
      of MS immunotherapy with IFN-medications is discussed.

PMID- 12497996
TI  - [Private nursing homes for mental patients and first steps of specialized
      psychiatric care in Russia].

PMID- 12497997
TI  - [Dynamics of demyelinating activity in various courses of progressive multiple
      sclerosis].

PMID- 12497998
TI  - [Paraneoplastic syndromes].

PMID- 12497999
TI  - [Optokinetic nystagmus: non-used diagnostic and therapeutic possibilities].

PMID- 12498000
TI  - [Hyperventilation disorders].

PMID- 12498001
TI  - The impact of beta-lactamases on the development of novel antimicrobial agents.
AB  - beta-Lactamases have been critical factors for the selection and development of
      beta-lactam-containing antibacterial agents for almost 60 years. New agents under
      investigation continue to be evaluated based on their interactions with beta
      lactamases. Oral carbapenems, penems and antimethicillin-resistant Staphylococcus
      aureus cephalosporins are all being selected for development, in part, because of
      their stability to hydrolysis by the beta-lactamases of their target organisms.
      beta-Lactamase inhibitors must selectively inhibit the major beta-lactamase
      groups appearing in current clinical isolates. For all agents, the multiplicity
      of beta-lactamases in single organisms or in mixed infections poses a new set of
      challenges requiring agents that can respond to enzymes with varying functional
      characteristics.

PMID- 12498002
TI  - GM-CSF treatment for Crohn's disease: a stimulating new therapy?
AB  - Crohn's disease (CD) has been classically viewed as an overactive intestinal
      immune response to the normal constituents of the gut flora. Most therapeutic
      strategies to date have tried to suppress this overactive adaptive immune
      response. Recently, a novel, rather alternative therapeutic strategy has been
      proposed, wherein the approach is to stimulate the innate immune system with
      growth factors. This review will take a closer look at this unconventional
      hypothesis and the data that support it, and will place the information in the
      context of some of the other biological and experimental therapies currently
      under consideration for the treatment of CD.

PMID- 12498003
TI  - Role of tumor necrosis factor in Crohn's disease.
AB  - Tumor necrosis factor-alpha (TNF alpha) is one of several pro-inflammatory
      cytokines that have been implicated in the pathogenesis of Crohn's disease (CD).
      Treatment with antibodies to TNF alpha has been shown to reduce mucosal
      inflammation in the disease, promote tissue healing, achieve and maintain
      remission, improve the CD activity index (CDAI) and improve the quality of life.
      The first part of this article reviews the role of TNF alpha in CD.

PMID- 12498004
TI  - Therapeutic inhibitors of tumor necrosis factor in Crohn's disease.
AB  - Therapeutic options for patients with refractory ulcerative colitis or Crohn's
      disease have recently been augmented by the introduction of biological therapies.
      The pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha is present in
      elevated concentrations in patients with inflammatory bowel disease and
      inhibitors of TNF alpha have proved effective as treatment. Strategies aimed at
      reducing TNF in patients with Crohn's disease, include the mouse/human chimeric
      monoclonal antibody, infliximab (Centocor Inc), the humanized monoclonal
      antibody, CDP-571 (Celltech Group plc), the human recombinant TNF receptor fusion
      protein, etanercept (Immunex Corp), and thalidomide. New approaches, including
      the use of soluble TNF receptors, appear promising. This article reviews the
      evidence of therapeutic inhibition of TNF.

PMID- 12498005
TI  - Tacrolimus Fujisawa.
AB  - Fujisawa has launched the immunosuppressant tacrolimus extensively for use in
      organ transplantation. The compound has also been developed for the treatment of
      atopic dermatitis, for which it has been launched in the US, Japan, Switzerland,
      Canada and Germany [425053], [426616], [435668], [447770]. Tacrolimus has also
      been developed for chronic rheumatoid arthritis (RA) and several other autoimmune
      diseases [351891], [352195], [360717]. By March 2002, tacrolimus had entered
      phase III trials for inflammatory bowel disease (IBD) in Japan [442503]. This
      evaluation will focus on the development of tacrolimus for this indication.

PMID- 12498006
TI  - Pleiotropic effects of HMG-CoA reductase inhibitors.
AB  - HMG-CoA reductase, in addition to being the rate-limiting enzyme in the
      cholesterol biosynthetic pathway, is involved in the regulation of receptors for
      low-density lipoprotein (LDL)-cholesterol. Clinical studies in men and women
      demonstrate that inhibitors of HMG-CoA reductase (statins), by reducing plasma
      cholesterol, may limit the development of atherosclerosis and reduce the risk of
      mortality and ischemic events. Preclinical evidence suggests that under
      controlled conditions of plasma cholesterol lowering, statins may have ancillary
      properties or pleiotropic effects, which may directly limit atherosclerosis
      progression. In this review, pleiotropic effects have been defined as 'ancillary
      properties of statins, which result in hepatic and/or vascular changes that may
      or may not be a consequence of inhibition of HMG-CoA reductase.' Beyond the LDL
      lowering activity of statins, improvements have been noted in endothelial
      dysfunction through direct stimulation of expression of such vasodilators as
      nitric oxide and/or reduction in vasoconstrictors. Factors associated with
      atherogenesis, such as monocyte adhesion to endothelial cells, macrophage
      production of proinflammatory molecules and matrix metalloproteases, smooth
      muscle cell proliferation and migration and macrophage-induced oxidation of LDL
      particles have also been reduced by various statins. It is unclear whether the
      observed pleiotropic effects are independent of LDL-cholesterol lowering or
      inhibition of HMG-CoA reductase, and whether they are clinically relevant;
      however, one can conclude that the pleiotropic effects appear to be a class
      effect of statins and can be attenuated by addition of the post-reductase
      product, mevalonate.

PMID- 12498007
TI  - Combination therapy with statins.
AB  - Statins effectively inhibit cholesterol synthesis and are currently the most
      commonly used drugs for the treatment of hypercholesterolemia. However, patients
      with familial hypercholesterolemia and those unwilling to take, or who cannot
      tolerate statins, and patients with combined hyperlipidemia require a combination
      treatment. Statins combined with cholesterol malabsorption, caused, e.g., by
      plant stanol esters or ezetimibe (Schering-Plough Corp/Merck & Co Inc), or with
      bile acid malabsorption, caused by bile acid binding resins or guar gum, inhibit
      compensatory increases in cholesterol synthesis and effectively lower LDL
      cholesterol levels. Combination therapy of statins with fibrates should be
      controlled by lipidology experts. Recent information on indications and
      advantages of combining statins with n-3 fatty acids, hormone replacement
      therapy, or niacin, will also be discussed.

PMID- 12498008
TI  - S-18886 Servier.
AB  - S-18886, the active isomer of S-18204, is a thromboxane A2 receptor antagonist
      with a long duration of action. The compound is under development by Servier for
      the potential treatment of cardiovascular diseases [269611]. By 2000, a clinical
      trial had been carried out in patients with coronary artery disease [389458];
      advanced clinical trials were ongoing in August 2001 [420310].

PMID- 12498009
TI  - Avasimibe Pfizer.
AB  - Avasimibe (also known as CI-1011 or PD-148515) is a selective acyl-coenzyme
      A:cholesterol O-acyltransferase (ACAT) inhibitory lipid-regulating agent under
      development by Pfizer (formerly Parke-Davis) for the potential treatment of
      hyperlipidemia and atherosclerosis. The compound is currently undergoing phase
      III clinical trials [371470].

PMID- 12498010
TI  - Pitavastatin Nissan/Kowa Yakuhin/Novartis/Sankyo.
AB  - Pitavastatin (nisvastatin) is an HMG CoA reductase inhibitor being developed
      jointly by Nissan, Kowa Kogyo, Novartis and Sankyo for the potential treatment of
      atherosclerosis and hyperlipidemia.

PMID- 12498011
TI  - Utilizing brain imaging for analgesic drug development.
AB  - Analgesia is defined as loss of pain sensation without loss of consciousness;
      pain may be acute or chronic. Acute pain is well understood and can be controlled
      with currently available analgesics. Chronic pain, however, is not effectively
      controlled with current analgesics and side effect profiles often limit the use
      of these agents. Currently there are: (i) no objective methods for defining pain
      or analgesia in humans; (ii) no objective methods for correlating efficacy of
      analgesics in animal testing with human testing; and (iii) no objective method of
      evaluating the efficacy of analgesics in painful conditions, including
      neuropathic pain in which adaptive or maladaptive changes evolve with time. A
      technological revolution in functional brain imaging in humans and animals offers
      new approaches to objective evaluation of analgesics and of clinical pain states.
      These approaches hold great promise for revolutionizing drug development at
      preclinical and clinical stages.

PMID- 12498012
TI  - COX-2 inhibition and the control of pain.
AB  - The discovery of the two isoenzymes of cyclooxygenase COX-1 and COX-2 and their
      separate functions, localization and regulation, has initiated the search for new
      and more selective inhibitors of prostaglandin biosynthesis. Selective COX-2
      inhibitors were developed in order to improve an anti-inflammatory and analgesic
      specificity and potency. The role of inducible COX-2 at the peripheral site of
      inflammation is well known. The discovery of COX-2 in the spinal cord suggests
      that it is responsible for spinal prostaglandin release in nociceptive processes
      following a peripheral inflammatory stimulus. In the future, selective COX-2
      inhibitors such as celecoxib (GD Searle & Co), rofecoxib (Merck & Co Inc) and the
      recently developed etoricoxib (Merck & Co Inc) may play an important role in the
      treatment of a wider range of pain conditions in addition to their present use as
      anti-inflammatory and analgesic drugs.

PMID- 12498013
TI  - Eletriptan Pfizer.
AB  - Pfizer has developed and launched eletriptan, a 5-HT1B/1D agonist, for the
      potential treatment of migraine with and without aura. Eletriptan has 6-fold
      greater affinity for the 5-HT1D receptor than sumatriptan, and a 3-fold greater
      affinity for the 5-HT1B receptor [249570]. Eletriptan pharmacology has also been
      evaluated in vitro in comparison with zolmitriptan (AstraZeneca plc) and
      naratriptan (GlaxoSmithKline plc) [290116].

PMID- 12498014
TI  - Avinza Elan.
AB  - Avinza is a once-daily morphine sulfate controlled-release formulation utilizing
      SODAS (Spheroidal Oral Drug Absorption System) technology developed by Elan and
      Ligand for the potential treatment of pain [220806], [223862]. This
      multiparticulate product is designed to provide a rapid onset of action together
      with a sustained therapeutic effect over 24 h. It is thought that once-daily
      administration should improve compliance and help eliminate breakthrough pain
      which is a feature of many twice-daily products, thereby providing better pain
      management [220806].

PMID- 12498015
TI  - Frovatriptan Vernalis.
AB  - Vanguard (now Vernalis) has developed frovatriptan, a selective 5-HT1B/1D partial
      agonist licensed from GlaxoSmithKline as a potential treatment for migraine
      [188478], [194382], [377863].

PMID- 12498016
TI  - Selective induction of tumor ischemia: development of vascular targeting agents
      for cancer therapy.

PMID- 12498017
TI  - Erlotinib OSI/Roche/Genentech.
AB  - Erlotinib (CP-358774, OSI-774, Tarceva), a quinazoline derivative, is an orally
      active epidermal growth factor receptor tyrosine kinase inhibitor under
      development jointly by Genentech, OSI (formerly Oncogene Science) and Roche, both
      as monotherapy and combination therapy for the potential treatment of solid
      tumors, including non-small-cell lung cancer (NSCLC) and pancreatic, breast, head
      and neck cancers [203487]. Development of the compound is most advanced for NSCLC
      and pancreatic cancer; in July 2001, phase III combination trials were initiated
      for NSCLC [416835]. In October 2001, phase III monotherapy trials in NSCLC and
      phase III combination trials in pancreatic cancer were also initiated [426704].
      In Japan, the compound was in phase I studies in January 2002 [439189].

PMID- 12498018
TI  - FR-901228 Fujisawa/National Cancer Institute.
AB  - The depsipeptide FR-901228 is a histone deacetylas inhibitor under development by
      Fujisawa and the National Cancer Institute as a potential treatment for neoplasm.
      By May 2002, phase II trials had commenced in the US [452248], [461017].

PMID- 12498019
TI  - Discounting or waiving patient co-payments and deductibles--an overview primer.

PMID- 12498020
TI  - High court to review arbitration ruling in RICO suit against HMOs.

PMID- 12498021
TI  - CMS named to enforce HIPAA transaction and code set standards HHS office for
      civil rights to continue to enforce privacy standards.

PMID- 12498022
TI  - HHS announces Medicare premium and deductible rates for 2003.

PMID- 12498024
TI  - Draft WHO guidelines on the use of vaccines and antivirals during influenza
      pandemics.

PMID- 12498023
TI  - Global Advisory Committee on Vaccine Safety, 20-21 June 2002.

PMID- 12498025
TI  - Safety culture: sustaining the strategy.

PMID- 12498026
TI  - Implementing PSM for non-chemical industries.

PMID- 12498027
TI  - Building a business case for AEDs.

PMID- 12498028
TI  - Maximizing skills retention.

PMID- 12498029
TI  - Signs of age in today's workforce.

PMID- 12498030
TI  - Pallets pack a punch.

PMID- 12498031
TI  - Restraints change for the better.

PMID- 12498032
TI  - More than they used to be.

PMID- 12498033
TI  - [Molecular targets in original drug research].
AB  - Selection of the molecular target, a macromolecule mediating the beneficial
      effects of the drug substance and thereby determining the mechanism of drug
      action, is of utmost importance in original drug research. Publication of the
      draft sequence of the human genome offers a plethora of new possible molecular
      targets to scientists. That should deeply impact on drug research of the next
      decades.

PMID- 12498034
TI  - [Neuroprotective effects of vinpocetine in vivo and in vitro. Apovincaminic acid
      derivatives as potential therapeutic tools in ischemic stroke].
AB  - The aim of the present study was to review neuroprotective therapy from the
      preclinical point of view as a potential tool for the treatment of stroke, as
      well as to discuss neuroprotective effects of the apovincaminic acid derivative
      vinpocetine (Cavinton). Our own in vivo and in vitro experiments were aimed at
      further characterizing pharmacological effects involved in the vinpocetine
      induced neuroprotection. The effect of vinpocetine on infarct volume (obtained by
      2,3,5-triphenyltetrazolium-chloride staining) was studied in permanent middle
      cerebral artery occlusion (MCAO) in rats (3 mg/kg i.p., 30 min postischemia).
      Vinpocetine treatment significantly decreased infarct volume (by 42%, p < 0.05)
      compared to control, which was better than the effect of nimodipine (17%) or MK
      801 (18%). Neurotoxicity measurements were made in primary cortical cell culture
      using LDH release as an indicator. Vinpocetine dose-dependently inhibited
      prolonged (24 h) or transient (15 min) glutamate, and transient N-metil-D
      aspartate (NMDA) or veratridine (0.1-1 mM) induced excitotoxicity (IC50 = 2-7 x
      10(-6) M). In these tests the neuroprotective potency of vinpocetine was lower
      than that of MK-801, but it was similar to those of flunarizine or nimodipine.
      These results together with former literature data indicate that apovincaminic
      acid derivatives possessing strong neuroprotective potential may play an
      important role in the therapy of ischemic stroke.

PMID- 12498035
TI  - [METAPRINT: a metabolic fingerprint].
AB  - METAPRINT, a metabolic fingerprint based on predicted metabolic pathways and
      corresponding potential metabolites, has been developed. Calculated drug-likeness
      parameters (logP and MW) have been added into METAPRINT to achieve metabolic
      discrimination among the members of a chemical library. The application of
      METAPRINT in the design of cassette dosing experiments is demonstrated on a
      library of alpha-1a antagonists. Cassette design was performed by maximizing the
      intracassette Euclidean distances between compounds in METAPRINT space, using
      Metropolis Monte Carlo simulated annealing. Calculated distances in METAPRINT
      space were in accordance with experimental data.

PMID- 12498036
TI  - [Formulation of advancing products of pulmonary medicine absorption].
AB  - The author introduces the various possibilities of the production of medical
      aerosols ensuring pulmonary absorption. He also mentions the method of selecting
      the auxiliary materials formulated with propellants, and describes the
      characteristics of norfluran Dymel 134 and apafluran HFC 227. In the experimental
      section, he handles the development of an anxiolitic byciclo-heptane-type
      aerosol, for which the aim was to develop a homogeneous liquid-phase aerosol. For
      this he used a Freon 12/114 mixture and Dymel 134 propellants in a solvent
      mixture of ethanol and ethanol-propylene glycol. The solubility of byciclo
      heptane could be significantly improved with beta-cyclodextrine. The formation of
      enclosure complex can be proved by IR spectrum, and the complete dissolution was
      furthered by the OH groups of the auxiliary material.

PMID- 12498037
TI  - [Sensitivity of NMR spectroscopy].
AB  - Modern high-resolution liquid-phase NMR spectroscopy offers a huge array of
      techniques in the structure elucidation of small molecules, including their
      geometrical and dynamical aspects. This "repertoir" however can only be utilized
      properly if detection sensitivity is sufficiently high. The sensitivity issue has
      therefore become a crucial aspect of utilizing NMR spectroscopy amidst the ever
      increasing challenges the pharmaceutical R+D activities face. In the present
      paper we discuss the importance of high detection sensitivity in the process of
      structure elucidation. We also give a short overview of the most important
      development strategies aimed at increasing the sensitivity of NMR signal
      detection.

PMID- 12498038
TI  - [EFfect of quinazolone-alkyl-carboxylic acid derivatives on the transmembrane
      Ca2+ ion flux mediated by AMPA receptors].
AB  - The excitatory neurotransmitter, Glu, plays a crucial role in many sensory and
      motor functions as well as in brain development, learning and memory and it is
      also involved in the pathogenesis of a number of neurological disorders,
      including epilepsy, Alzheimer's and Parkinson's diseases. Therefore, the study of
      Glu receptors (GluRs) is of therapeutical importance. We showed here by
      fluorescence monitoring of transmembrane Ca2+ ion fluxes in response to (S)-alpha
      amino-3-hidroxi-5-metil-4-izoxazol propionic acid ((S)-AMPA) on the time scale of
      0.00004-10 s that Ca2+ ion influx proceeds through faster and slower
      desensitizing receptors. Pharmacological isolation of the slower and faster
      desensitizing AMPA receptor was possible by fluorescence monitoring of Ca2+ ion
      translocation in response to (S)-AMPA in the presence and absence of various 2
      methyl-4-oxo-3H-quinazoline-3-alkyl-carboxilic acid derivatives (Qxs): the acetic
      acid Q1 inhibits the slower desensitizing receptor response specifically, while
      the acetyl-piperidine Q5 is a more potent inhibitor of the faster desensitizing
      receptor response. In addition, spontaneous interictal activity, as induced by
      high [K+] conditions in hippocampal slices, was reduced significantly by Q5,
      suggesting a possible anticonvulsant property of Q5. Substitutions of Qxs into
      the GluR2 S1S2 binding core were consistent with their effect by causing variable
      degree of S1S2 bridging interaction as one of the main determinants of AMPA
      receptor agonist activity. The exploitation of differences between similar
      receptors will be important in the development and use of drugs with high
      pharmacological specificity.

PMID- 12498039
TI  - [Influence of storage conditions on the physical aging of amorphous
      polyvinylpyrrolidone].
AB  - The aim of the present study was to examine the structural changes of amorphous
      polyvinylpirrolidone, associated with the physical ageing, by the determination
      of the free volume of the polymer and to find a correlation between the
      structural changes of the polymer and the physical stability of tablets
      containing it. The water absorption from the storage medium resulted in the
      glassy to rubbery transition of amorphous polyvinylpyrrolidone at room
      temperature. This spontaneous transition was not continuous in the case of PVP
      K25. Not only the actual water content but the storage history determines the
      free volume distribution of the samples. The structural changes associated with
      the physical ageing influence the physical stability of solid dosage forms
      containing this polymer.

PMID- 12498040
TI  - [Huntington chorea: genetics and biochemistry, diagnosis and therapy].
AB  - Huntington chorea (HC) is a serious neurodegenerative disease. Its genetic
      background has recently been discovered by positional cloning due to the enormous
      progress in molecular biology. This disease is caused by the mutation of CAG, a
      changeable, repetitive Citosin-Adenin-Guanin trinucleotide sequence. The protein
      coded by this sequence is called huntingtin. The role of huntingtin is known
      neither in mutant nor in normal proteins, despite several hypotheses on this
      matter. Nevertheless, in connection with the number of the CAG repeat many
      regularities have been proved which can be used in diagnosis and also in
      prediction of the disease. The latter is of great importance since the treatment
      of HC is still limited to symptomatic therapies, however numerous therapeutical
      approaches are being observed. In the future, real treatment of this disease is
      expected from gene therapy. Until the application of this method, the most
      effective approach is prevention, on the basis of genetic counseling.

PMID- 12498041
TI  - [Chemical discrimination of compounds possessing an amino group].
AB  - Cyclic 1,3-amino alcohols have been successfully resolved via lipase-catalysed O
      acylation of their Z derivatives, using vinyl butyrate as acyl donor in different
      ether solvents. A direct HPLC method was developed for the monitoring of the
      resolutions. Most of the screened lipases preferred the S enantiomer. Both
      alcohol and ester enantiomers were obtained in ee > 90% after gram-scale
      resolutions. A new isothiocyanato-type CDA, (1S,2S)- or (1R,2R)-1,3-diacetoxy-1
      (4-nitrophenyl)-2-propyl isothiocyanate [(R,R)- or (S,S)-DANI], was designed for
      the indirect HPLC enantioseparation of primary and secondary amino compounds. The
      new reagent can be readily synthetized in optically pure form (> or = 99.5%)
      after a straightforward two-step synthesis. It is stable chemically and
      stereochemically both in the solid and in the solution phase. It is available in
      both enantiomeric forms, allowing the appropriate selection of the elution
      sequence. The kinetics of derivatization was studied in detail for alpha-amino
      acids and for beta-blockers. The quantitativeness of reactions was ensured by
      optimization of reaction conditions (pH, reagent excess, temperature). As
      concerns the HPLC analyses of the thiourea derivatives formed, significant
      differences were found between selectivities of the organic modifiers applied; in
      most cases, MeOH proved much more effective than MeCN with respect to both
      retention times and resolutions. In conclusion, the new CDA was capable of the
      resolution of most of the investigated analytes.

PMID- 12498042
TI  - [IMZ implants in the treatment of the shortened dental arch in the upper and
      lower jaws].
AB  - The aim of this study was to evaluate the long-term prognosis after insertion of
      510 IMZ-implants in case of free-end situations of the upper and lower jaw and
      prosthodontic restoration. We examined 222 patients prospectively who were
      treated in a dental practice because of uni- or bilateral free-end situation
      between 1984 and 1996. Affected and crowned teeth which were neighbouring the
      implant-based suprastructure, were blocked with these by use of bridge
      restorations or attachments. In all the other cases purely implant-based bridge
      or single-tooth restorations were inserted. Clinical parameters as for example
      the peri-implant tissue reaction, sulcus depths as well as implant mobility and
      radiological findings were documented and evaluated statistically. In case of
      pure implant-based suprastructures we found six implant losses (1.2%), whereas in
      case of combined tooth-implant-based prosthodontic restorations 20 losses (3.9%)
      were found.

PMID- 12498043
TI  - [Lateral periodontal cyst. A case report].

PMID- 12498044
TI  - [Immediate implant-supported bridge for the mandible. A new treatment concept].

PMID- 12498045
TI  - [Stem cells between research and social dialogue].

PMID- 12498046
TI  - [The stem cell debate: in favor of ethical clarification].
AB  - Stem cell research raises ethical issues, the grounds for which however are
      fairly unclear. As a form of fundamental research, it should be assessed
      according to the same classical ethical criteria. The strategic scientific
      question of the priority of adult stem cells versus embryonic stem cells cannot
      be dogmatically answered in advance, but rather contextually. The question of the
      moral status of the embryo outside the woman's body will always involve personal
      beliefs. But legislation will have to regulate this issue from a "middle-of-the
      road" position reflecting the convictions of most of the citizens (e.g., embryos
      will be protected, but not the same as already-born persons).

PMID- 12498047
TI  - [Plasticity of stem cells: a change of paradigm?].
AB  - Until a few years ago, an interest in stem cells, mostly of hematopoietic origin,
      was limited to a relatively small representation of scientists and clinicians
      seeking to understand the role of these rare cells in tissue homeostasis and to
      utilize their remarkable potential to regenerate an adult tissue following
      transplantation. Over the last few years, an ability of bone marrow-, brain-,
      muscle- and other tissue-derived stem cells to branch off, move between tissues
      and contribute to their repair was discovered. According to this novel view, at
      least a subset of stem cells may alter their fate in a manner that is more
      plastic and dynamic than previously thought, causing a fascination with these
      cells to spread to nearly all clinical disciplines. Expectations are high: stem
      cells are considered a future remedy for major diseases of our civilization.
      There are more questions raised than answers, and pressure grows to extend the
      knowledge and accelerate its implementation.

PMID- 12498048
TI  - [New developments in hematopoietic stem cell transplantation].
AB  - Transplantation of hematopoetic stem cells is established therapy today. It
      includes transplants from bone marrow, peripheral blood or cord blood. Leukemias,
      lymphoproliferative disorders, aplastic anemia and congenital disorders of the
      bone marrow are main indications for allogeneic, lymphoproliferative disorders,
      leukemias, solid tumors and severe autoimmune disorders main indications for
      autologous transplants. New developments, such as reduced intensity conditioning
      approaches and selective donor lymphocyte infusions open the procedure to older
      patients and to those with coexisting other morbidities. Whenever possible, the
      transplant is integrated into the treatment plan from diagnosis. The individual
      risk profile determines choice of procedure and time point. Diagnosis and age as
      sole criteria no longer suffice. Hematopoetic stem cell transplantation might
      serve in the future as a model for stem cell transplants for other organs.

PMID- 12498049
TI  - [Stem cells from cord blood: current status and future potential].
AB  - Umbilical cord blood is rich in hematopoietic stem cells. At birth, it can be
      collected, HLA-typed and stored. Cord blood is successfully used since over 10
      years as source of transplantation of hematopoietic stem cells, in addition to
      bone marrow and mobilized peripheral blood stem cells. Allogeneic
      transplantations are performed between HLA-identical siblings and from HLA
      matched unrelated donors. Most recipients of cord blood are children with
      Leukemia or genetic disorders, but also increasingly adolescents and adults.
      Based on the promising results, cord blood banks with kryopreserved, HLA-typed
      cord blood samples from anonymous donors are set up worldwide, ready to be used
      as allogeneic stem cell graft. In addition, so-called "private" cord blood banks
      have been set up, providing the possibility to store cord blood at birth from
      healthy children with no affected family member for a possible autologous stem
      cell transplantation in the future if the child later develops a disease such as
      Leukemia. For several reasons, however, this procedure has been scientifically as
      well as ethically challenged. To date, there is no established indication for an
      autologous cord blood transplantation. Nevertheless, the plasticity and
      multipotency of adult stem cells, which has been recently discovered, could lead
      to a possible autologous use of cord blood stem cells for different indications
      in the field of regenerative medicine (cell- and organ replacement/regeneration).
      So far, however, this remains speculatative. Research in the field of stem cell
      development and differentiation in the next decade will try to find some answers.

PMID- 12498050
TI  - [Stem cells from cord blood: legal and ethical questions of transplantation and
      banking].
AB  - Transplantation and banking of stem cells from cord blood raise different legal
      and ethical questions. Who owns the cord blood? Does transplantation infringe the
      physical integrity of the neonate? And if so, who has to give her or his consent?
      In any case, legal representation by the neonate's guardians has to be guided by
      the "welfare of the child". Banking stem cells from cord blood may be private or
      public. Private banking causes difficulties concerning the right to health care
      and the issues of justice and equity. Public banking too raises complex legal
      issues, e.g. protection of potential recipients from life-threating illnesses at
      the one hand and the right of the donor to autonomy in disclosing information at
      the other.

PMID- 12498051
TI  - [Embryonic stem cells: new possible therapy of degenerative diseases].
AB  - The capacity of embryonic stem (ES) cells for virtually unlimited self-renewal
      and differentiation has opened up the prospect of widespread applications in
      biomedical research and regenerative medicine. The use of these cells would allow
      to overcome the problems of donor tissue shortage and also implant rejection if
      the cells are made immunocompatible with the recipient. Since the derivation in
      1998 of human ES cell lines from pre-implantation embryos, considerable research
      is centered on their biology, on how differentiation can be encouraged towards
      particular cell lineages and also on means to enrich and purify derivative cell
      types. In addition, ES cells may be used as an in vitro system not only to study
      cell differentiation but also to evaluate the effects of new drugs and the
      identification of genes as potential therapeutic targets. This review will
      summarize what is known about animal and human ES cells with particular emphasis
      on their application in four animal models of human diseases. Present studies of
      mouse ES cell transplantation reveal encouraging results but also technical
      barriers that have to be overcome before clinical trials can be considered.

PMID- 12498052
TI  - [About easy answers].
AB  - In the last few months all aspects of stem cell research--biomedical, ethical,
      legal--have been given broad space in the print and electronic media. Biologists,
      physicians, lawyers and ethicists covered many of the facets and have thus laid a
      solid foundation of basic information for a very wide public. The political
      discussions in the context of the new Swiss Federal law governing the use and
      protection of supernumerary fertilized oocytes in IVF are about to completely and
      irreversibly change the character of these discussions. Information has been
      superseded by lobbying for particular interests. Before society has had time to
      find widely accepted answers to the many questions raised by stem cell research
      and to come to terms with it, economic pressure groups demand a legal framework
      in which therapeutic cloning is permitted. At the same time, patents on genes and
      stem cells are to be introduced to finance research. Together, the two claims
      shed a new light on stem cell research. Both claims tend to polarize public
      opinion. Well-known patterns will dominate the communication process and allow
      both sides to shirk the real issues: what are the broadly accepted ethical
      answers to the many questions raised by stem cell research? Again scientists will
      argue for the freedom of research in an economic context on behalf interest
      groups. Their closeness to interest groups will undermine their own credibility,
      the credibility of science and the public confidence. It is to be hoped that
      other scientists will continue to independently argue the case for their
      research, to talk about it and its problems and to discuss them in an
      interdisciplinary exchange with their colleagues from other branches of science
      with a view to a consensus acceptable to a majority of the public. This
      consensus, even if it has to be reviewed and redefined constantly in the light of
      new research, will give scientists the inner security needed for their work. Only
      the dialogue with society can create the necessary understanding for science and
      thus serve best its interest.

PMID- 12498053
TI  - [Pancreatic stem cells--a new therapeutic option for the treatment of type 1
      diabetes mellitus?].
AB  - The recent discovery of heretofore unknown, multipotential stem cells within the
      embryonic and adult islets of Langerhans suggests new therapeutic options for the
      treatment of diabetes mellitus type 1. These cells are characterised by the
      expression of the neural stem cell marker nestin and by their ability to
      differentiate ex vivo into pancreatic endocrine, exocrine and hepatic phenotypes
      with the expression of insulin, glucagon, amylase, cytokeratin-19 as well as
      liver specific proteins such as alpha-fetoprotein. The insulinotropic hormone
      glucagon-like peptide-1 enhances the differentiation of these nestin positive
      islet derived progenitor (NIP) cells into insulin secreting cells by activation
      of IDX-1, the key transcription factor for the differentiation into a beta-cell.

PMID- 12498054
TI  - [Ethical aspects of embryonic stem cell research].
AB  - Research using embryonic stem cells raises a variety of ethical questions, which
      will be explored in this article. At the core of the ethical controversy is the
      question of the status of the embryo and its availability for research. A range
      of countries have approved the use of "supernumerous" embryos from in-vitro
      fertilization. But ethical problems also arise in reproduction medicine, the
      informed consent of affected couples, and the targeted production of embryos and
      egg cell donation for research. The author discuss some of these neglected issues
      and develops suggestions for comprehensive ethical reflection.

PMID- 12498055
TI  - [Embryos and embryo-like entities: problem of definition in the draft of the
      Swiss embryonic research law].
AB  - At the end of May 2002, the draft of the Swiss "Federal Act on Research on
      Surplus Embryos and Embryonic Stem Cells" (EFG, Embryonic Research Act) reached
      the pre-legislative consultation stage. Under certain conditions, it would allow
      research on "surplus" embryos from in-vitro fertilization, and the derivation of
      embryonic stem cells from surplus embryos for research purposes. The EFG draft
      defines an embryo as "the developing organism from the point of nuclear fusion
      until the completion of organ development". New technological developments show
      that embryo-like entities can also be created without nuclear fusion having taken
      place. It remains unclear how to treat embryonic entities that don't fall under
      the draft's narrow definition of an embryo. Expanding this definition would be a
      welcome improvement.

PMID- 12498056
TI  - [Prenatal stem cell transplantation: from bench to bedside].
AB  - Prenatal stem cell transplantation is a novel, promising therapeutic option for
      genetic disorders, which is now at the edge of moving from preclinical research
      into clinical application. The first clinical experience shows that inborn
      diseases, which lead to a severe immunodeficiency, can be treated successfully
      inutero. No therapeutic success has been achieved in genetic disorders which do
      not severely affect the immune system. Therefore, new strategies to improve the
      success are being developed, including e.g., graft modification, prenatal
      conditioning of the fetus, postnatal re-transplantation after prenatal induction
      of immune tolerance, and fetal gene therapy using autologous fetal stem cells.
      The use of non-hematopoietic (e.g. mesenchymal) or pluripotent stem cells will
      most probably lead to an expansion of the spectrum of indications in genetic
      diseases for this novel treatment. At the same time, however, ethical
      implications, in particular regarding fetal gene therapy and the use of
      pluripotent stem cells must be evaluated.

PMID- 12498057
TI  - Care of the elderly: the problem of clinical inertia.

PMID- 12498058
TI  - Making computers work for us.

PMID- 12498059
TI  - Engineering hearing.

PMID- 12498060
TI  - Yukon Gold.

PMID- 12498061
TI  - All in my head.

PMID- 12498062
TI  - Sensory mystery.

PMID- 12498063
TI  - Islands of sight.

PMID- 12498064
TI  - Getting a feel for touch.

PMID- 12498065
TI  - When good hearing goes bad.

PMID- 12498066
TI  - Aromatherapy: therapeutic applications of plant essential oils.
AB  - As is the case with many other complementary and alternative therapies in the
      United States, the use of essential oils or aromatherapy has increased in recent
      years. The term "aromatherapy" can be confusing because it is used to describe a
      wide range of practices involving odorous substances. In order to advise and
      better inform patients, physicians and other health professionals should be able
      to differentiate between aesthetic applications of odors and clinical uses of
      essential oils (essential oil therapy). They also should be able to identify key
      issues regarding safety and efficacy. There is a growing body of evidence in the
      scientific literature suggesting that plant essential oils, alone or in
      combination with other therapies, may be beneficial in treating a number of
      health conditions. This article describes essential oil therapy and identifies
      key issues for practice.

PMID- 12498068
TI  - Big changes ahead in JCAHO's survey process, so start working now.

PMID- 12498067
TI  - Sensory processing disorders.
AB  - Most people are able to effectively process and respond to the sensory stimuli of
      daily life. But people who have sensory processing disorders struggle to form
      meaningful responses to sensory stimuli. As a result these individuals often
      exhibit problems with coordination, sensory-seeking or sensory-avoiding
      behaviors, and sensory modulation. The concept of sensory processing disorders
      stems from the work of occupational therapist Jean Ayres, Ph.D. Her work has
      launched a sensory-based treatment approach, primarily practiced by occupational
      therapists. This article outlines the theories supporting the notion of sensory
      processing disorders, options for assessment and treatment, and research on the
      efficacy of treatment.

PMID- 12498069
TI  - Patient satisfaction planner. Decision-aid tool helps patient communication.

PMID- 12498070
TI  - Patient satisfaction planner. Make a good thing better: one hospital's rallying
      call.

PMID- 12498071
TI  - Patient satisfaction planner. Bedside registration: wireless system's a hit.

PMID- 12498072
TI  - NCQA: quality measures up for third year in a row.

PMID- 12498073
TI  - Improve quality with systems thinking. Part 1.

PMID- 12498074
TI  - [Localization of NADPH diaphorase in the central nervous system of the bivalve
      mollusc Cristaria tuberculata].
AB  - By histochemical and electron histochemical methods, NADPH-diaphorase was
      discovered in neurons and their processes of all ganglia of the central nervous
      system (CNS) of Cristaria tuberculata. Small cells predominated among neurons
      containing NADPH-diaphorase. Ultrastructural localization of the enzyme was
      detected on the perinuclear membrane and membranes of endoplasmic reticulum,
      cytoplasmic granules and cytosol. In the majority of cells, the reaction product
      was commonly found in cytoplasmic granules-cytosomes. We studied peculiarities of
      synaptic contacts between nitrogen oxide synthesizing neurons and their
      processes. In active synaptic areas, a sediment was discovered on the internal
      surface of pre- and postsynaptic membranes.

PMID- 12498075
TI  - [Cytological and molecular changes in the atypical case of accelerated human
      aging].
AB  - A complex research of cells of a patient with unusual form of premature ageing
      was made. The clinical picture is not typical for any of known forms of
      hereditary premature aging--progerias. Skin fibroblasts of the patient AG has
      limited proliferation capacity in vitro. It was shown by fluorescent
      immunochemical hybridization (FISH-method), that the level of stable chromosome
      aberrations in AG blood lymphocytes was characteristic of aged 55-65 years,
      though as he was only 26 years old. Some characteristic peculiarities, typical
      for progerias, were found in the reaction of skin fibroblasts of AG to growth
      factors addition. Some clinical and biochemical peculiarities are results rather,
      than reasons of the disease. The conclusion is that the premature ageing in this
      case is a manifestation of Werner's syndrome--one of hereditary forms of
      accelerated senescence.

PMID- 12498076
TI  - Cell cycle and its parameters in flowering plants.
AB  - Data on the duration of cell cycle and its phases in meristems are reviewed for
      170 species from 93 genera of 38 families of higher plants. The reviewed cell
      cycle parameters are submitted in tabulated form, including taxonomic and
      anatomical characteristics of particular subjects, methods, experimental
      conditions, duration of cell cycle and its phases, and references. The influence
      of environmental factors on the cell cycle and temperature dependence of cell
      cycle parameters are considered in addition to certain features and causes of
      daily dynamics of mitotic index. Special attention is paid to the problem of
      comparability of different results of determination of cell cycle duration. As
      shown below, the only correct comparison of cell cycle parameters in different
      species is that, which is based on the evidence provided at species-specific
      optimum temperatures. A rather simple method for determining the optimum
      temperature of cell division and growth is based on the analysis of root growth
      rate. Critical temperature points are defined to serve for determination of
      optimum temperature for the cell cycle. As shown below, retardation of growth
      rate at low temperatures results from the proportional increase in the duration
      of cell cycle phases, while at the minimum temperature the morphological
      characteristics of meristem remain unchanged. Cell division anomalies or
      morphogenesis disruption that occur as cell cycle parameters change may be due
      presumably to the shock temperature action within the tolerant limits. Our
      experiments have suggested that the rhythm of illumination may exert essential
      influence on the parameters, structure and stationarity of the cell cycle.

PMID- 12498077
TI  - [Somatic polyploidy in neurons of the gastropod mollusca. III. Mitosis and
      endomitosis in the postnatal development of neurons in the Succinea snail central
      nervous system].
AB  - General morphology of chromatin, the number of chromosomes and chromocenters in
      normal condition and at the increase of bivalent cation (Ca2+, Mg2+)
      concentration were studied with the purpose to reveal mechanisms of
      polyploidization of neuron nuclei in the snail Succinea lauta (Gastropoda,
      Pulmonata). The morphology of nuclei was studied on squashed preparations. Normal
      diploid mitoses are described in the cerebral ganglia. A possibility is supposed
      that part of neurons or neuroblasts in the central nervous system (CNS) of
      succineid snail may divide mitotically. It has been shown that the basic
      mechanism of neuron postnatal growth is endomitotic polyploidization of nuclei.
      The transition from ordinary mitosis to polyploid cycles occurs via restitutional
      (polyploidizing) mitosis (4c2n-->4c4n). The next endocycles are carried out by
      means of classic endomitosis up to reaching the highest ploidy levels--4096n-
      16,384n. The study of general morphology of chromatin and chromocenters at normal
      condition and at artificial compactization enabled us to exclude any probability
      of polyteny in the CNS of lauta.

PMID- 12498078
TI  - [Stabilization of chromonema--one of the highest compactization levels--by
      visible light in the presence of ethidium bromide].
AB  - This paper deals with the ultrastructure and behavior of interphase chromatin and
      metaphase chromosomes of L-197 culture cells under experimental conditions, which
      help to reveal the chromonemal level of chromosomal structure after the treatment
      of living cells with 0.1% Triton X-100 and 3 mM CaCl2. In these conditions, the
      chromonemata can be seen as dense chromatin fibers with thickness about 100 nm.
      Such chromosomes, whose chromonemal substructure after the treatment with
      hypotonic solution (10 mM Tris-HCl), look like loose chromosomal bodies composed
      of elementary 30 nm DNP fibrils. On the other hand, if chromosomes, in which
      chromonemal levels were revealed by 3 mM CaCl2, were treated with etidium bromide
      and then illuminated by light with length wave about 460 nm, no chromosomal
      decondensation in hypotonic conditions is observed. Chromonemata in chromosomes
      stabilized by light retain their density and dimensions. It is very important
      that chromonemata in stabilizated chromatin of metaphase chromosome keep specific
      connections between themselves and also general trend in their composition inside
      the chromosome. Thus, we have found conditions for observation of chromonemal
      elements in metaphase chromosome, providing the possibility for future three
      dimensional investigation of chromonema packing in mitotic chromosomes.

PMID- 12498079
TI  - [Meiosis spindle formation and chromosome behavior in diploid potatoes with
      'fused spindles' mutation].
AB  - Chromosomal behaviour and spindle morphology were studied in microsporogenesis of
      two kinds of diploid potato clones: with normal meiosis, and with "fused
      spindles" (fs) occurring during the second meiotic division from prometaphase II
      (proMII) to telophase II (TII). For the first time, morphological effect of fs
      was found at the late proMII stage to be expressed as two interrelated processes:
      1) abnormal chromosome movement, which resulted in joining two groups of
      chromosomes in the central zone of meiocytes, and 2) abnormal formation of two
      spindles in the direction to two division poles instead of four poles that
      actually led to the formation of a united bipolar spindle. Thus, it is not the
      fusion of two parallel spindles but the formation of united bipolar spindle that
      constitutes fs abnormality, while the parallel co-orientation of two spatially
      separated meiotic spindles is a norm in diploid potato. These primary
      abnormalities detected at proMII resulted in abnormalities at its subsequent
      meiotic stages: formation of fused spindle and united metaphase plate at MII,
      bipolar chromosome segration at anaphase II, formation of two telophase nuclei at
      TII and dyads at the tetrad stage. The results obtained evidence the polar
      division disturbance in diploid potato clones with fs abnormality.

PMID- 12498081
TI  - [DNA-containing polygonal structures detected in somatic nuclei of Bursaria ovata
      during preparation to cryptobiosis].
AB  - Supramolecular chromatin organization of the somatic nucleus (macronucleus--Ma)
      was studied in a free-living unicellular eukaryotic organism, the ciliate
      Bursaria ovata Beers 1952, at two late successive stages of its encystment (in
      the state of preparation to cryptobiosis). A modified Miller's method (Sergejeva
      et al., 1987) and the same technique in combination with high resolution DNA
      autoradiography were used. In chromatin spread preparations of Ma, not labeled by
      3H-thymidine, numerous electron dense structures (rounded, stick-like and
      polygonal) were revealed, along with rarely occurring typical supramolecular
      chromatin structures, such as nucleosomic and not nucleosomic threads,
      nucleomeres, chromomeres, rosette-like looping chromatin, and electron dense
      chromonemes (Fig. 1). For DNA visualizing in the revealed polygonal structures,
      the vegetative cells (trophonts) of B. ovata were inoculated into the culture
      medium, containing 3H-thymidine and food (ciliates Paramecium caudatum). Here,
      the ciliates passed through 3-4 successive cell division cycles, thus
      progressively accumulating the radioactive DNA precursor in Ma. After washing the
      ciliates in 3H-thymidine-free culture medium, the process of their encystment was
      induced, and Ma were isolated by hand from the ciliates being at two late
      successive stages of encystment. Isolated Ma were dispersed in the low ionic
      solutions, as described elsewhere (Sergejeva et al., 1987). The carbon shadowed
      electron grids, that contained spread Ma preparations, were individually coated
      with photographic emulsion, according to the loop interference method (Angelier
      et al., 1976a; Bouteille, 1976). After a 6 month exposure at 4 degrees C,
      thymidine incorporation was revealed in fibril crowds, rosette-like structures
      (Fig. 2), and crystal-like plates of different size and morphology (Fig. 3). In
      all our experiments, non-specific localization of radioactive DNA precursor was
      not observed. The above data confirm undoubtedly our earlier assumption
      (Sergejeva et al., 1987; Sergejeva, Bobyleva, 1988) that the Ma chromatin of
      Bursaria may undergo crystallization during encystment, i.e. in the state of
      preparation to cryptobiosis. The present data enable us first to suggest that the
      looping rosette-like chromatin may be transformed into crystal-like structures
      ("exotic liquid crystal structures") by means of a peculiar loop packing within
      the limits of an individual resette (Fig. 2-4), these structural transformations
      taking place without any visible loop destruction. In this paper, we first
      describe new morphological types of polygonal plates, differing from those
      earlier reported elsewhere for the Ma of Bursaria (Sergejeva, Bobylova, 1988),
      and also from the plates earlier described in studies on liquid crystals both in
      vivo and in vitro (see: Gianonni et al., 1969; Lerman, 1974; Livolant, 1991:
      Leforestier et al., 1993, 1997, 1999). The technical approaches used in the
      present work enabled us to obtain, for the first time, a direct evidence of the
      presence of DNA in the crystallized structures of somatic nuclei of ciliates
      during their preparation to cryptobiosis, the DNA-containing polygonal structures
      being highly morphologically diverse. Further studies into the reasons of this
      diversity are needed.

PMID- 12498082
TI  - [Free radical oxidation of DNA and its biomarker oxidized guanosine(8-oxodG)].
AB  - Endogenous free radicals, in particular, reactive species of oxygen, nitrogen,
      chlorine cause DNA oxidation which is potentiated by exogenous prooxidant
      factors. The free radicals cause various DNA damages. This review highlights one
      of them, oxidative modification of guanosine, and also modern methods of the
      estimation of oxidized guanosine (8-oxodG) content. The numerous data on an
      induction of 8-oxodG in DNA by exogenous genotoxicants in vitro and in vivo are
      presented. 8-oxodG is used as a biomarker of DNA oxidation, accompanying some
      human diseases.

PMID- 12498084
TI  - [Regulation of opioid receptors by thyroliberin analogues].
AB  - The ability of thyroliberin (TRH) to interact with opioid receptors (OR) was
      studied using radioligand analysis. TRH did not influence specific binding of
      [3H]-naloxone, but increased affinity of high affinity binding sites for the
      ligand in a dose-dependent manner. TRH also decreased affinity of low- affinity
      binding sites. Kinetic analysis of low-affinity binding sites suggests the
      existence of at least two subpopulations of OR, which differed in their affinity
      to naloxone and mode of interaction with TRH. TRH acted as non-competitive and
      competitive inhibitor of receptor binding sites with the lowest and moderate
      affinity, respectively. The allosteric pattern of TRH influence on OR with high
      and the lowest affinity to naloxone was suggested. TRH analogues were estimated
      for their ability to change in OR binding characteristics. The level of [3H]-DADL
      specific binding was not influenced by the peptides tested but the affinity was
      changed. Blind control experiment showed the ability of the TRH relative
      substances to increase in affinity of d-receptors could be ranked in the row:
      dihydroorotyl-hystidyl-prolinamide > TRH > methionyl-asparagyl-phenylalaninamide.
      This is consistent with ability of these compounds to influence the dopaminergic
      events.

PMID- 12498085
TI  - [Hepatoprotective effects of gamma-L-glutamylhistamine].
AB  - The influence of gamma-GluHA and glutarylhistamine on the lipid peroxidation,
      cholesterol, phospholipid and liver aminotransferase activity was investigated
      using carbon tetrachloride-induced model of subacute liver damage. Pretreatment
      of rats with gamma-GluHA and glutarylhistamine prevented liver necrosis and
      normalized activity of alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) in blood plasma, lipid peroxidation in the liver and
      plasma, lipid profiles and cholesterol content in the liver and plasma.

PMID- 12498086
TI  - [Effect of treatment with perftoran on the course of experimental uveitis, lipid
      peroxidation and activity of antioxidant defense enzymes].
AB  - Experimental uveitis is characterized by a pronounced lipid peroxidation (LPO) in
      damaged tissues of eye, which is complicated by reduced activity of the
      antioxidant enzymes, SOD and catalase. The intensification of LPO was also found
      in blood serum and hepatic tissue. However, hepatic lipid peroxidation was
      accompanied by compensatory increase of catalase activity. The activity of
      antioxidant defence enzymes decreased in blood, whereas catalase was activated in
      hepatic tissue. The therapeutic effect was accompanied by a decrease of LPO
      products and increase of activity of the antioxidant enzymes in all tissues.
      Treatment of uveitis with gentamycin and, especially, perftoran reduced
      inflammatory events.

PMID- 12498088
TI  - [Glutamine metabolism in the liver after partial hepatectomy in chronic
      hepatitis].
AB  - A long-term treatment of female rats with CCl4 caused a decrease of glutamine
      content in the liver. This decrease may be attributed to stable reduction of
      glutamine synthetase activity and slightly elevated (or unchanged) phosphate
      dependent glutaminase. Partial hepatectony (15-20% of the liver) did not
      normalise glutamine metabolism.

PMID- 12498087
TI  - [Effect of UV-radiation on the level of ascorbic acid, SH-groups, and activity of
      glutathione reductase in the eye lens].
AB  - The effect of UV radiation in vitro on the level of ascorbate, SH-groups and
      glutathione reductase activity in the soluble fraction of bovine eye lens was
      studied. UV-Irradiation increased NADPH-oxidoreductase activity, the level of
      ascorbate oxidation and decreased the content of SH-groups and activity of
      glutathione reductase. Significant activation of the NADPH-oxidoreductase
      activity in the presence of ascorbate and Cu2+ was observed after UV-irradiation.
      It is suggested that ascorbate may play an important role in the UV-induced lens
      pathology.

PMID- 12498089
TI  - [Transfection of eucaryotic cells using cytochrome CYP450 2B6 gene: sensitivity
      to cyclophosphamide].
AB  - Sensitivity of 293 human epithelial kidney cells transfected by human cytochrome
      CYP450 gene to cyclophosphamide was investigated. Transfection was carried out by
      plasmid DNA containing CYP2B6 gene complexed with cationic liposomes. Liposomes
      were prepared from mixture of cationic lipids and cholesterol at different molar
      ratios. Experimental protocol included the following steps: transfection of
      epithelial kidney cells by complexes of plasmid DNA-cationic liposomes, clone
      selection in the medium with antibiotic Geneticin G418, selected clone harvesting
      and their treatment by cyclophosphamide as following cytotoxicity evaluation. It
      was shown that addition of 0.25 mM of cyclophosphamide resulted in death of 40
      45% transfected cell population.

PMID- 12498090
TI  - [Monoclonal anti-NSE-antibodies: purification, characterization, and immunoenzyme
      analysis].
AB  - The results of NSE purification procedure, as well as hybridoma technology of
      anti NSE monoclonal antibodies synthesis are presented. The employment of this
      procedure yielded highly purified NSE preparation. The immunization of BALB/C
      mice with NSE preparation led to sensitization of the immunocompetent cells,
      which could form hybridomes, producing the anti-NSE monoclonal antibodies, after
      the confluence with myeloma cells Sp 2/0-Ag 14. The ELISA test-system for NSE
      analysis was developed on the basis of highly purified NSE preparation and
      monoclonal anti-NSE antibodies. This system was characterized by high
      specificity, accuracy and reliability. This system may be recommended for
      analysis of blood-brain barrier functions in the neurological and psychiatric
      diseases.

PMID- 12498091
TI  - [Effect of GABA and pyracetam on mitochondrial ADP phosphorylation in
      experimental hypokinesia].
AB  - Long-term limitation of motor activity of male rats is accompanied by impairments
      of mitochondrial ADP phosphorylation in liver and heart. The most significant
      changes were observed after 15 and 45 days of hypokinesia. Administration of GABA
      and pyracetam to animals subjected to hypokinesia induced a tendency to
      "normalization" of ADP phosphorilation processes.

PMID- 12498092
TI  - [Intensity of pentose phosphate metabolism of carbohydrates in various brain
      areas in normal and starved animals].
AB  - The activities of key enzymes of pentose phosphate pathway, glucose-6-phosphate
      dehydrogenase (G-6 PD) and 6-phosphogluconate dehydrogenase (6-PGD), were studied
      in cytoplasmatic fractions of brain cortical (limbic, orbital, sensorimotor
      cortex) and subcortical (myelencefalon, mesencefalon, hypothalamus) structures of
      rats subjected to starvation for 1, 2, 3, 5 and 7 days. Short-term starvation (1
      3 days) caused activation of 6-GPD and 6-PGD both in cortical and subcortical
      structures. Long-term starvation for 5-7 days caused a decrease of activities of
      the pentose phosphate pathway enzymes in all studied structures. It is suggested
      that enzymes of pentose phosphate pathway in nervous tissues are functionally and
      metabolically related to glutathione system and during starvation they indirectly
      participate in the regulation lipid peroxidation processes.

PMID- 12498093
TI  - [Comparative effect of partial opiate agonists buprenorphine and butorphanol on
      the phospholipid composition of hepatocytes plasma membranes during hemorrhagic
      shock in cats].
AB  - Comparative effects of the partial opiate agonists buprenorphine and butorphanol
      on the phospholipid composition of liver cell plasma membranes were investigated
      in cats under conditions of hemorrhagic shock. Buprenorphine administration (0.03
      mg/kg) normalized the level of phosphatidylinositol. The higher dose (0.3 mg/kg)
      induced additional disturbances in the phospholipid composition of liver cell
      plasma membranes by increasing the content of phosphatidylserine and by
      decreasing the contents of sphingomyelin and lysophosphatidylcholine. The
      protective effect of butorphanol on liver cells was more pronounced than that of
      buprenorphine.

PMID- 12498094
TI  - [Effect of nifedipine and verapamil on cytosolic glucocorticoid receptors in
      hemorrhagic shock].
AB  - Function of rat liver cytosolic glucocorticoid receptors in the haemorrhagic
      shock and the effects of verapamil and nifedipine were investigated. Nifedipine
      administration normalised hepatic receptor functioning affected by the shock.
      Verapamil administration to animals subjected to shock treatment caused further
      suppression of the receptor functioning. Both drugs reduced blood corticosterone
      level in hemorrhagic animals up to control level. Verapramil potentiated
      hypotension and this deteriorated the course of posthamorrhagic period. This
      effect may be at least partially attributed to verapramil-induced inhibition of
      glucocorticoid receptor type II. Nifedipine maintained BP in the subnormal level
      and reduced the number of animals with the decompensated shock course, which is
      probably associated with its positive influence on glucocorticoid receptor
      properties and permits to recommend an introduction of this drug into the complex
      therapy of the shock.

PMID- 12498095
TI  - [Changes in the system of antioxidant blood defence in newborns with different
      pathology].
AB  - Blood antioxidant enzymes (superoxide dismutase, catalase, ceruloplasmin) were
      investigated in gestational ages and diseases. Low activity of blood superoxide
      dismutase and catalase were observed in premature babies and in newborns after
      acute and chronic hypoxia. In hemolytic disease the activity of antioxidant
      enzymes of newborns was significantly higher than in healthy infants. This work
      demonstrates advantages of haemosorbtion compared to exchange blood transfusion.
      So the antioxidant activity in blood, decreased after blood transfusion, remained
      at a high level after haemosorbtion. Any deficiency of antioxidant enzymes in
      newborns may lead to toxyc oxygen effects. Antioxidants are potential therapeutic
      agents in the above mentioned conditions.

PMID- 12498096
TI  - [The activity of NAD(P)-dependent dehydrogenases in blood lymphocytes in children
      and adolescents with different duration of insulin-dependent diabetes mellitus].
AB  - The levels of blood lymphocyte NAD(P)-dependent dehydrogenases were investigated
      in children and teenagers with different duration of insulin-dependent diabetes
      mellitus (IDDM). The level of some NAD(P)-dependent dehydrogenases changed
      proportionally in dependence of IDDM duration and insulin therapy did not restore
      their activities to the normal level. It is suggested that these changes may
      reflect decrease of energy metabolism and plastic processes in blood lymphocytes
      from diabetic children and teenagers reflecting. These changes correspond to
      altered functional reactivity of immunocompetent cells and represent metabolic
      basis of immunopathogenic complications of IDDM.

PMID- 12498097
TI  - [Computer model of 3D structure of cytochrome P450 2B4].
AB  - Cytochromes P450 (CYPs) play an important role in the oxidative metabolism of
      xenobiotics. Three-dimensional structures of CYPs are needed to study structure
      function relationships in their molecules and interaction with partner proteins.
      Experimental determination of eucaryotic CYPs 3D structures is difficult because
      of hydrophobic membrane anchors and surface hydrophobic regions that prevent
      their crystallization. Replacement of surface hydrophobic amino acids by
      hydrophilic residues without any changes in protein structure and function can
      help to solve this problem. Such modification can be proposed using the analysis
      of 3D model of protein. In this work computer aided 3D structure of microsomal
      P450 2B4 (CYP2B4) was modeled for the further prediction of surface mutations for
      hydrophilization of the protein surface. The model of 3D structure of CYP2B4 was
      constructed by homology with CYP2C5 Model optimization was made by energy
      minimization and molecular dynamics simulation of protein molecule in water
      environment. The model was verified by using special statistic software and by
      comparison with the experimental data on the substrate recognition site, redox
      partner binding sites and chemical modification of the protein surface.

PMID- 12498098
TI  - Neuroimmune relationships in perspective.

PMID- 12498099
TI  - Sympathetic nervous system interaction with the immune system.

PMID- 12498100
TI  - Mechanisms by which cytokines signal the brain.

PMID- 12498101
TI  - Neuropeptides: modulators of immune responses in health and disease.

PMID- 12498102
TI  - Brain-immune interactions in sleep.
AB  - This chapter discusses various levels of interactions between the brain and the
      immune system in sleep. Sleep-wake behavior and the architecture of sleep are
      influenced by microbial products and cytokines. On the other hand, sleep
      processes, and perhaps also specific sleep states, appear to promote the
      production and/or release of certain cytokines. The effects of immune factors
      such as endotoxin and cytokines on sleep reveal species specificity and usually
      strong dependence on parameters such as substance concentration, time relative to
      administration or infection with microbial products, and phase relation to sleep
      and/or the light-dark cycle. For instance, endotoxin increased SWS and EEG SWA in
      humans only at very low concentrations, whereas higher concentrations increased
      sleep stage 2 only, but not SWS. In animals, increases in NREM sleep and SWA were
      more consistent over a wide range of endotoxin doses. Also, administration of pro
      inflammatory cytokines such as IL-6 and IFN-alpha in humans acutely disturbed
      sleep while in rats such cytokines enhanced SWS and sleep. Overall, the findings
      in humans indicate that strong nonspecific immune responses are acutely linked to
      an arousing effect. Although subjects feel subjectively tired, their sleep
      flattens. However, some observations indicate a delayed enhancing effect on sleep
      which could be related to the induction of secondary, perhaps T-cell-related
      factors. This would also fit with results in animals in which the T-cell-derived
      cytokine IL-2 enhanced sleep while cytokines with immunosuppressive functions
      like IL-4 and L-10 suppressed sleep. The most straightforward similarity in the
      cascade of events inducing sleep in both animals and humans is the enhancing
      effect of GHRH on SWS, and possibly the involvement of the pro-inflammatory
      cytokine systems of IL-1 beta and TNF-alpha. The precise mechanisms through which
      administered cytokines influence the central nervous system sleep processes are
      still unclear, although extensive research has identified the involvement of
      various molecular intermediates, neuropeptides, and neurotransmitters (cp. Fig.
      5, Section III.B). Cytokines are not only released and found in peripheral blood
      mononuclear cells, but also in peripheral nerves and the brain (e.g., Hansen and
      Krueger, 1997; Marz et al., 1998). Cytokines are thereby able to influence the
      central nervous system sleep processes through different routes. In addition,
      neuronal and glial sources have been reported for various cytokines as well as
      for their soluble receptors (e.g., Kubota et al., 2001a). Links between the
      immune and endocrine systems represent a further important route through which
      cytokines influence sleep and, vice versa, sleep-associated processes, including
      variations in neurotransmitter and neuronal activity may influence cytokine
      levels. The ability of sleep to enhance the release and/or production of certain
      cytokines was also discussed. Most consistent results were found for IL-2, which
      may indicate a sleep-associated increase in activity of the specific immune
      system. Furthermore, in humans the primary response to antigens following viral
      challenge is enhanced by sleep. In animals results are less consistent and have
      focused on the secondary response. The sleep-associated modulation in cytokine
      levels may be mediated by endocrine parameters. Patterns of endocrine activity
      during sleep are probably essential for the enhancement of IL-2 and T-cell
      diurnal functions seen in humans: Whereas prolactin and GH release stimulate Th1
      derived cytokines such as IL-2, cortisol which is decreased during the beginning
      of nocturnal sleep inhibits Th1-derived cytokines. The immunological function of
      neurotrophins, in particular NGF and BDNF, has received great interest. Effects
      of sleep and sleep deprivation on this cytokine family are particularly relevant
      in view of the effects these endogenous neurotrophins can have not only on
      specific immune functions and the development of immunological memories, but also
      on synaptic reorganization and neuronal memory formation.

PMID- 12498103
TI  - Neuroendocrinology of autoimmunity.
AB  - The HPA axis is fundamental for long-term survival and protection from the
      ravages of autoimmune disease. Continuing investigations suggest that the
      hypothesis linking susceptibility to autoimmune disease and a hyporesponsive HPA
      axis is somewhat simplistic. Instead, data from a number of different human
      diseases and from preclinical studies in a variety of models have suggested a
      more complicated picture. Alterations in the diurnal rhythms of ACTH, cortisol,
      and immune parameters appear to be linked to severity of disease. The use of low
      doses of steroids timed to target disrupted diurnal immune system changes in
      patients with RA may reduce the unfortunate side effects of long-term steroid
      use. Studies in cancer patients have related alterations in diurnal cortisol to
      survival. Whether differences in individual cortisol profiles are predictive of a
      deterioration in symptoms of autoimmune disease remains to be established.
      Responsiveness of the HPA axis to subtle challenges such as the dexamethasone
      suppression test and the related dexamethasone-CRF test suggest that there are
      different sub-populations of patients with RA and MS and these may have
      confounded earlier, apparently contradictory, studies. These different responses
      may be related to the severity of the disease. That these HPA axis differences
      can be altered beneficially through the use of antidepressants, as has been shown
      in MS, may impact on future health care strategies. However, reports of negative
      developments in arthritis associated with SSRI use suggest that the SSRIs may be
      unsuitable under some circumstances. The link of behavioral differences to
      alterations in neurotransmitter changes associated with disease is intriguing and
      opens new avenues of research. These future studies will require input from
      neuroscientists, neuroendocrinologists, psychologists, and immunologists working
      with the clinical specialties already involved in treating patients with
      autoimmune disease. These multidisciplinary studies reflecting the increased
      importance of hormonal and neurotransmitter involvement with the immune system
      hold great promise for the future.

PMID- 12498104
TI  - Systemic stress-induced Th2 shift and its clinical implications.

PMID- 12498105
TI  - Neural control of salivary S-IgA secretion.

PMID- 12498106
TI  - Stress and secretory immunity.

PMID- 12498107
TI  - Cytokines and depression.

PMID- 12498108
TI  - Immunity and schizophrenia: autoimmunity, cytokines, and immune responses.
AB  - As is evident from the present account, there is no single or persuasive argument
      that signals emanating from the immune system are directly involved in the
      etiology of schizophrenia. We do not even know if we are dealing with a single
      disorder with a single causality; almost certainly we are not. The precise
      etiology of schizophrenia, as with so many neurological disorders, remains
      obscure. However, there is abundant evidence in schizophrenia of mutual
      dysregulation of neuronal function and immune system activity. Although this
      evidence is not always consistent, a pattern emerges suggesting aspects of immune
      activity being involved in the pathology of neuronal development that
      characterizes schizophrenia. Exposure to infective agents, HLA associations,
      autoimmune associations, disturbances in lymphocyte populations, and cytokine
      imbalances with a skew toward Th2 activity are supportive of this view. That the
      evidence is not always consistent is a testament to the complexity and
      heterogeneity of the disorder, to confounding by antipsychotics that themselves
      are immunomodulatory, and to the multifaceted nature, with all its checks and
      balances, of the immune system itself.

PMID- 12498109
TI  - Cerebral lateralization and the immune system.

PMID- 12498110
TI  - Behavioral conditioning of the immune system.

PMID- 12498111
TI  - Psychological and neuroendocrine correlates of disease progression.

PMID- 12498112
TI  - The role of psychological intervention in modulating aspects of immune function
      in relation to health and well-being.

PMID- 12498113
TI  - [Vaccine prophylaxis: questions without answers].

PMID- 12498114
TI  - [Biochemical characterization of viral hepatitis in humans, using and not using
      narcotics].
AB  - AIM: To compare biochemical changes in viral hepatitis (VH) in drug abusers (DA)
      and non-abusers (NA). MATERIAL AND METHODS: Hepatic function was examined in 1125
      patients with parenteral hepatitis, 540 of them were DA. Transaminases tests and
      protein precipitation tests were made at the disease height and in convalescence.
      RESULTS: In DA patients with VH biochemical changes were found more frequently
      than in NA. In convalescence, elevation of alaninaminotransferase was higher in
      DA than in NA. CONCLUSION: Drug abuse in VH patients influences biochemical
      indices. In DA with VH correlations of biochemical indices with the disease
      severity are less frequent than in NA, while changes of biochemical indices
      reflecting hepatic function occur more frequently and persist longer.

PMID- 12498115
TI  - [Complex therapy of chronic viral hepatitis, occurring in combination with
      opisthorchosis].
AB  - AIM: To design and substantiate an effective combined therapy scheme for patients
      with chronic viral hepatitis (CVH) and chronic opisthorchiasis (CO). MATERIAL AND
      METHODS: 10 patients with CHB and 12 patients with CHB + C in the presence of CO.
      All the patients have undergone clinical and device examinations before the
      treatment and in the course of therapy with biltricide and reaferon. RESULTS:
      Patients with CVH at the stage of moderate activity and in the phase of virus
      replication received antihelminthic therapy with biltricide which caused neither
      complications nor deterioration, antihelminthic effect was observed in 20 of 22
      patients. In a month, the patients started on reaferon given for therapy of
      hepatitis. As a result, all the patients improved clinically with normalization
      of biochemical blood parameters. Markers of viral hepatitides disappeared in 17
      of 22 patients. CONCLUSION: Combined therapy of CVH in active process in the
      presence of CO may include antihelminthic and antiviral treatment and should be
      staged.

PMID- 12498116
TI  - [Prospects for interferon therapy in chronic hepatitis C with normal transaminase
      levels].
AB  - AIM: To study effectiveness of recombinant interferon-alpha (Ifna) in patients
      with chronic hepatitis C with normal transaminases. MATERIAL AND METHODS: 26
      patients with positive tests for abHCV and RNA HCV with a normal level of
      alaninaminotransferase (AlAT) entered the study. 16 patients of the test group
      received recombinant Ifna three times a week in a dose 3 mln IU. Mean duration of
      interferon therapy was 7.44 +/- 4.27 months. Control group consisted of 10
      patients with natural course of the disease. Biochemical, virusological and
      morphological examinations were conducted in all the patients. The patients were
      followed up for 1.5-2 years, on the average. RESULTS: Treatment with recombinant
      Ifna was well tolerated. A persistent positive virusological response after the
      treatment was achieved in 25% of the test patients. They exhibited improvement of
      histological structure of the liver. In control group the dynamics was opposite.
      CONCLUSION: In patients with chronic hepatitis C with normal transaminases level
      interferon therapy improves structure of hepatic tissue. Puncture biopsy of the
      liver is the main method which determines the validity of the treatment and its
      efficacy.

PMID- 12498117
TI  - [Some aspects of evaluating endogenous intoxication in patients with acute
      dysentery].
AB  - AIM: To evaluate endogenic intoxication in patients with acute dysentery (AD) by
      examination of substances of low and medium molecular mass (LM and MM) in
      different body media. MATERIAL AND METHODS: 122 patients with acute dysentery
      were tested for LM and MM substances by M. Ya. Malakhova in plasm, red cells,
      urine in the course of the disease. RESULTS: Concentration of LM and MM
      substances in patients with AD was much higher compared to healthy subjects in
      all the examined fluids at the height of the disease. In decline of clinical
      symptoms the studied concentrations diminished, in early convalescence the
      substances were at normal levels in red cells and urine being higher in plasm.
      Maximal changes of the LM and MM substances' concentrations were noted in a
      severe course of AD. CONCLUSION: In acute bacterial dysentery concentration of LM
      and MM substances in blood plasm, red cells and urine depend on the period of the
      disease course and AD severity. This may indicate the degree of endogenic
      intoxication in these patients.

PMID- 12498118
TI  - [Epidemiologic and economic efficacy of massive prophylaxis of influenza and
      other acute respiratory viral infections using curantil in Moscow enterprises].
AB  - AIM: To evaluate epidemiological and cost-effect value of curantil in "in-office"
      prophylaxis of influenza and acute respiratory diseases (ARD) in Moscow. MATERIAL
      AND METHODS: Curantil was given once a week for 4-5 weeks in a dose 50 mg with 2
      3-week intervals in autumn peaks of ARD and influenza epidemics. Participation of
      the population was 50-70% maximum. Prevailing influenza viruses causing epidemic
      in 1990-1991, 1991-1992 were A(H3N2) and B, respectively; ARD were caused by
      parainfluenza viruses, PC, P, mycoplasma etc. Efficiency index and rate were
      calculated: EI = a/b; ER = (a-b)/a x 100 where a--morbidity in the test group, b-
      in the control. Cost effectiveness was estimated by sick leaves pays for workers
      equal to the number protected by curantil and wages for those who worked instead
      of the ill workers or by the cost of the saved production. RESULTS:
      Epidemiological efficiency at enterprise 1 in autumn 1990 was the following (70%
      covarage): EI = 4.4, ER = 77.2%; in winter epidemic EI = 2.7, ER = 62.4%
      (covarage 50%). Close results were obtained in the next epidemiological season.
      In autumn in the enterprise 2 EI = 3.9; ER = 74.3%. Curantil prophylaxis at
      enterprise 1 protected 53 workers and saved 11278.88 roubles. CONCLUSION:
      Curantil effectiveness, wide spectrum of action, safety in oral administration 50
      mg once a week make curantil convenient for mass prevention of influenza and ARD.

PMID- 12498119
TI  - [Connection between severity of the course of tick-borne encephalitis with the
      concentration of interleukin-2 and interleukin-6 in blood].
AB  - AIM: To test IL-6 and IL-2 serum concentrations as indirect prognostic indicators
      in tick-borne encephalitis (TBE) course. MATERIAL AND METHODS: 13 TBE patients'
      sera were examined for IL-2 and IL-6. RESULTS: IL-6 was not detected in patients
      with TBE fever but was detected in meningoencephalytic TBE. CONCLUSION: TBE
      patients demonstrate a positive correlation between the disease severity and
      serum IL-6. This criterion is proposed as a prognostic factor of a TBE course.

PMID- 12498120
TI  - [Status of cellular immunity in patients with Astrakhan fever].
AB  - AIM: To ascertain regularities of development of cellular immunity in patients
      with Astrakhan fever (AF) with reference to AF severity, treatment and course.
      MATERIAL AND METHODS: Cellular factors of immunity--relative and absolute
      contents of T-lymphocytes (early and late), T-helpers and T-suppressors, B
      lymphocytes, neutrophils (early and late)--were studied in 75 patients with AF
      (63 patients with moderate and 12 patients with severe disease) in the course of
      the disease progression (weeks 1-5). The patients received antibacterial
      treatment--doxicyclin, rifampicin and doxicycline in combination with alpha 2
      realdiron and gamma-reaferon. RESULTS: Examination of immunocompetent cells has
      revealed suppression of T- and B-immunity for 2 weeks in moderate AF and 3 weeks
      in severe AF. The number of T-helpers was low for 3 weeks while of T-suppressors
      rose beginning from week 2. Immunoregulatory index Tx/Tc remains low till the end
      of the disease. The number of early and late neutrophils increased since weeks 2
      of the disease in moderate and week 3 in severe AF. CONCLUSION: Doxicycline
      efficiency was higher than that of rifampicin. Interferon preparations decrease
      relative number of early and late T-lymphocytes, neutrocytes and T-helpers but
      their absolute number is at the control level. Relative content of T-suppressors
      and B-lymphocytes is as in controls but their absolute content is higher.

PMID- 12498121
TI  - [Clinico-epidemiologic characteristics of streptococcal (group A) infections at
      the current time].

PMID- 12498122
TI  - [Local cases of three-day malaria in the Moscow area].

PMID- 12498123
TI  - [Clinical and structural parallels in changes of the myocardial conduction system
      in diphtheria patients].
AB  - AIM: Comparison of the results of clinical device investigations of the heart
      with morphological autopsy evidence in diphtheria. MATERIAL AND METHODS: Hearts
      of 309 patients with diphtheria aged 25 to 80 years and 60 hearts of patients who
      died of diphtheria were investigated using ECG, echo-CG, doppler echo-CG, Holter
      ECG monitoring, biochemical tests of blood. Structural study of cardiac
      conduction included examination of the sinus-atrial node, atrioventricular node
      and bundle regarding the adjacent myocardium. RESULTS: Variants of structural
      functional state of the myocardium and conduction system are explained by
      variability of the pathological processes which arose due to individual features
      of the conduction system structure and location, relationships with the
      myocardium. In acute diphtheria (day 1-10) dystrophic, necrobiotic and vascular
      disorders prevailed followed on days 11-30 by inflammation ending in
      myocardiosclerosis. Nodes and bundles of the conduction system are affected less
      frequently than the myocardium. CONCLUSION: A correlation exists between
      structural state of the cardiac conduction system and variants of clinical
      affection of the heart in diphtheria.

PMID- 12498124
TI  - [Papillomavirus infection in men].

PMID- 12498125
TI  - [Liver involvement in secondary infections in HIV-infected patients].
AB  - AIM: To determine spectrum and frequency of hepatic lesions, clinical, laboratory
      and morphological characteristics of hepatic pathology in secondary diseases in
      HIV-infected patients. MATERIAL AND METHODS: In 1991 to 2002 the authors observed
      59 HIV-infected patients with hepatic affection caused by opportunistic
      infections and tumors. The examination included biochemical tests of blood,
      immunological tests, biopsies and tests of the autopsy material for CMVDNA, T.
      Gondii, M. Tuberculosis. Polymerase chain reaction, puncture biopsy of the liver,
      ultrasound investigation of the abdominal organs. 57 lethal outcomes were
      registered. RESULTS: Hepatic lesion was of tuberculous origin in 42.4%, CMV--in
      16.9%, toxoplasmic--in 6.8%. 3 patients had fungal infection. Cancer of the liver
      was diagnosed in 18.6%. Clinical picture in most of the examinees was not clear
      and did not correspond to morphological severity of the condition. Ultrasound
      detected hepatic lesions if they were caused by CMV infection, toxoplasmosis and
      malignant tumors. Biochemical parameters were changed moderately. Patients with
      CMV hepatitis showed significant rise in the activity of GGT and AP. CONCLUSION:
      Apart from virus hepatitis B, C and D, the liver of HIV-infected patients got
      affected with tuberculosis, CMV-infection, toxoplasmosis, cancer. Hepatitis in
      HIV-infected subjects unrelated to viruses or medicines indicates a generalized
      disease, late stage of HIV-infection with a fall of the number of CD4-lymphocytes
      under 100 cells/microl.

PMID- 12498126
TI  - [Complexity in clinical diagnosis of internal diseases of acutely-progressive
      forms of tuberculosis].

PMID- 12498127
TI  - [Course of tuberculosis in patients with HIV infection].
AB  - AIM: To evaluate clinical features of tuberculosis in correlation with HIV
      infection duration. MATERIAL AND METHODS: 117 patients with HIV-infection were
      divided into three groups: HIV-infected in the presence of long-standing
      tuberculosis (group 1), HIV- and tuberculosis-infected simultaneously (group 2),
      tuberculosis-infected 5-10 years after getting HIV-infection. CONCLUSION:
      Clinical picture and course of tuberculous infection in HIV-infected patients
      depend on the time of getting HIV-infection and are determined by the severity of
      T-cell immunodeficiency. RESULTS: Tuberculosis runs its usual course in patients
      of groups 1 and 2. In group 3 tuberculosis ran atypically, had lethal outcome due
      to either tuberculosis or opportunistic infections.

PMID- 12498128
TI  - [Tuberculous pericarditis in clinical practice].

PMID- 12498129
TI  - [Clinical and morphofunctional characteristics of hydatid liver echinococcosis].
AB  - AIM: To examine the levels of aspartate aminotransferase (AsAT) and
      alaninaminotransferase (AlAT) in homogenates of hepatic biopsies from patients
      with echinococcosis. MATERIAL AND METHODS: Clinical, biochemical examinations,
      ultrasonic examination of the liver were made in 49 patients with hydatid
      echinococcosis of the liver and 5 control patients operated on for extrahepatic
      pathology. Morphological picture of the liver was examined with light microscopy.
      AsAT and AlAT activity in hepatic tissue were estimated with 2,4
      dinitrophenilhydrazin method. RESULTS: There were marked cellular and
      extracellular disorders and significant lowering of transaminases in the
      pericystic zone of hepatic tissue vs such indices for far from the echynococcal
      cyst sites of the liver. CONCLUSION: In hepatic echinococcosis hepatic tissue
      undergoes diffuse alteration associated with severe morphofunctional disorders
      which require adequate preoperative preparation of the patients, in postoperative
      period adequate intensive therapy is needed.

PMID- 12498130
TI  - [Epidemiologic features of cryptosporidiosis in Turkmenistan].
AB  - AIM: To study epidemiological characteristics of cryptosporidosis (CS) in
      conditions of arid climate which contributes to suppression of the immune status
      of the organism. MATERIAL AND METHODS: 1935 patients were treated for acute
      intestinal infection with watery diarrhea in Ashkhabad hospital in 1994-1999.
      Monocryptosporidiosis was diagnosed in 511 of them. Also, 46 mothers of CS
      children and 32 foci of the infection were examined. Cryptosporidial oocysts in
      the feces were detected by the Fulleborn's method. The preparations were stained
      by Ziehl-Neelsen. RESULTS: CS incidence in Turkmenistan was high, especially in
      children aged 2 to 7 years and adults aged 31-35 and 46-50 years. CS occurs
      throughout the year, but the morbidity is higher in summer and winter. The
      leading route of transmission is alimentary, it prevails over contact, watery and
      perinatal.

PMID- 12498131
TI  - [Analysis of the structural-functional status of nucleoli from cardiomyocytes,
      fibroblast-like cells and endotheliocytes in patients with familial obstructive
      hypertrophic cardiomyopathy].

PMID- 12498132
TI  - [Prevalence of main risk factors for cardiovascular diseases and efficacy of long
      term multifactoral prophylaxis].
AB  - AIM: To study prevalence of cardiovascular disease risk factors (CRF) in relation
      to sex, age, occupation as well as efficiency of active long-term multifactorial
      prophylaxis in the groups of active intervention (AI) and observation. MATERIAL
      AND METHODS: The comparison group consisted of 1848 male and 1643 female
      volunteers. 8326 males and 13,116 females entered the group of active
      intervention and observation. RESULTS: Risk factors correction led to lowering of
      mean systolic and diastolic arterial pressure, smoking intensity, overweight, to
      improvement of wellbeing of cardiovascular patients. The number of examinees with
      several risk factors decreased while those free of risk factors increased. There
      was also a reduction in the number of days of temporary disability. In AI group
      total mortality, coronary heart disease and cerebral event mortality fell
      manifold. CONCLUSION: Five- and ten-year active multifactorial "in-office"
      prophylaxis decreased frequency and intensity of risk factors. Lowering of
      cardiovascular disease incidence was associated with a 44.4% decrease in the
      number of days on sick-leave. The presence of cardiovascular diseases,
      combination of risk factors in healthy subjects and in cardiovascular patients in
      the beginning of the study significantly increased total mortality,
      cardiovascular mortality in comparison and active intervention groups. Active
      multifactor prophylaxis in persons with risk factors and cardiovascular diseases,
      especially in combination with risk factors, in the beginning of the study
      reduced total mortality and mortality of cardiovascular disease in active
      intervention.

PMID- 12498133
TI  - [Seeking medical advice in myocardial infarction].
AB  - AIM: Seeking medical advice (SMA) in myocardial infarction (MI) has been reviewed
      for 22 (1977-1998) years. Causes of late SMA have been analysed. MATERIAL AND
      METHODS: SMA was studied in 4093 MI patients. In 757 cases the time of SMA was
      considered depending on the diagnostic category, intensity of pain syndrome,
      first or repeated MI. RESULTS: SMA early after MI (within the initial hours) in
      1977-1991 was low. Later (in 1992-1998), the situation became worse. SMA depends
      on sex and age. Young men and old women seek medical advice late after MI. Early
      SMA does not depend on awareness of having ischemic heart disease. The majority
      of the patients are unaware of the risk of the first MI hours, while half of them
      do not know symptoms of MI. CONCLUSION: As SMA in MI is a behavioral
      characteristic of the population, the problem is social and can be solved only by
      relevant education of the population.

PMID- 12498134
TI  - [Status of microcirculation and cardiodynamics in ischemic heart disease patients
      with decreased left ventricular fraction and their response to carvedilol].
AB  - AIM: Assessment of microcirculation in IHD patients at preclinical stage or in
      those with initial symptoms of cardiac failure, clarification of relationship
      between parameters of microcirculation and cardiodynamics. MATERIAL AND METHODS:
      A blind cross-over trial was made to compare skin microcirculation and
      cardiodynamic parameters in response to a short carvedilol course and beta
      blocker anaprilin in 40 patients with ischemic heart disease with angina of
      effort (NYHA class I-IV, ejection fraction under 45%). RESULTS: IHD with initial
      symptoms of cardiac failure had a congestion-spastic type of microcirculation
      defect. Microcirculatory picture and cardiodynamics were related. CONCLUSION:
      Compared to anaprilin therapy, treatment with carvedilol enhanced capillary blood
      flow and improved cardiodynamics.

PMID- 12498135
TI  - [Echocardiographic changes associated with risk of developing embolic
      complications in patients with ischemic stroke].
AB  - AIM: To study echocardiographic parameters associated with embolic complications
      in patients with cardioembolic and other pathogenetic subtypes of ischemic
      stroke. MATERIAL AND METHODS: 330 patients with ischemic stroke (IS) were
      examined. Transthoracal echocardiography was made in all the patients,
      transesophageal echocardiography was performed in 53 (16.1%) patients. The
      patients were divided into two groups: 104 (31.5%) patients who survived
      cardiocerebral embolism (group 1), 226 (68.5%) patients with other pathogenetic
      subtypes of stroke (group 2). RESULTS: Cardiac pathology was detected in 220 of
      330 (66.7%) examinees with ischemic heart disease in 50.0% and 51.3% patients of
      group 1 and 2, respectively; infectious-inflammatory diseases--in 27.9 and 4.4%,
      respectively (p < 0.0001), other diseases (mitral prolapse, aneurysm and
      interatrial defect, idiopathic arhythmia) in 25.0 and 5.3% patients, respectively
      (p < 0.0001). Left atrial myxoma was diagnosed in 1.9% patients of group 1.
      CONCLUSION: Echocardiographic changes associated with a risk of embolic
      complications were visualized in all pathogenetic subtypes of ischemic stroke. In
      cardioembolic stroke echocardiography detected most frequently prolapse with
      myxomatous degeneration of the cusps and mitral vegetations, mitral failure,
      calcinosis of the mitral ring, local hypokinesia of the left ventricle, dilation
      and thrombosis of the left atrium. Rare changes, indicating cerebral embolism,
      include replaced aortic and mitral valves, mitral stenosis, cardiac tumor,
      aneurysm and defect of the interatrial septum.

PMID- 12498136
TI  - [Complex assessment of efficacy and tolerance of metoprolol CR/ZOK in treating
      hypertension].
AB  - AIM: To study efficacy and tolerance of betaloc ZOK (Astra-Zeneca, UK) in
      patients with stage I-II (WHO classification) essential hypertension. MATERIAL
      AND METHODS: 27 patients were enrolled in the study (13 men and 14 women, mean
      age 40.6 +/- 1.57 years). Complete physical examination, ambulatory blood
      pressure monitoring, assessment of central hemodynamics, microcirculation were
      made before the treatment and on the treatment week 8. RESULTS: Monotherapy with
      betalok ZOK (50-100 mg/day) resulted in a significant lowering of mean daily, day
      and night systolic and diastolic arterial pressure. Variability index was
      reduced, circadian rhythm of blood pressure did not change. 28% had to take
      diuretics (arifon or hypotiazide). CONCLUSION: Betaloc ZOK (50-100 mg) is highly
      effective in patients with mild to moderate essential hypertension.

PMID- 12498137
TI  - [Bronchial reactivity and mucosal bioamines as criteria for acute bronchitis
      becoming chronic].
AB  - AIM: To study bronchial reactivity and sensitivity with consideration of
      histamine, serotonin and catecholamines concentration in bronchial mucosa in
      patients with acute bronchitis (AB) as possible criteria of its becoming chronic.
      MATERIAL AND METHODS: Before the treatment 116 patients with verified AB were
      examined using inhalation provocative tests (IPT) with histamine, serotonin and
      obsidian in increasing doses. Also, external respiration function was studied.
      IPT were repeated after the course of treatment. RESULTS: 87 of 116 AB patients
      exhibited high bronchial sensitivity and reactivity to inhalations of histamine,
      serotonin, obsidian. In parallel, there was a rise in the levels of histamine and
      serotonin and a fall in the level of catecholamines in bronchial mucosa (alveolar
      macrophages, lymphocytes, neutrophils, mast and APUD-cells). Changes in
      monoamines concentration in bronchial mucosa were relevant to activity of
      bronchial inflammation and the presence of obstructive syndrome. CONCLUSION:
      Persistent bronchial hyperreactivity to inhalations of histamine and obsidian
      along with high histamine levels and low level of catecholamines in alveolar
      macrophages, lymphocytes and mucus is a criterion of bronchitis transformation to
      chronic one.

PMID- 12498138
TI  - [Effect of highly active antiretroviral therapy on the immune system in patients
      with HIV infection].

PMID- 12498139
TI  - [Obstructive breathing disorders in sleep: epidemiology, pathophysiology,
      clinical symptoms, treatment].

PMID- 12498140
TI  - [Prospects for pulse oximetric monitoring for screening diagnosis of
      apnea/hypoapnea in sleep].

PMID- 12498141
TI  - [Cytokine system and respiratory system diseases].

PMID- 12498142
TI  - [Clinico-pharmacological approach to choosing non-prescription analgesics].

PMID- 12498143
TI  - Analysis of the random distribution of station-tested pigs based on their genetic
      merit.
AB  - The analysis was conducted on the national database of the station tests carried
      out between May 1996 and February 2001, using the Hungarian Large White (LW) and
      Hungarian Landrace (LR) breeds, and the A-line of the Ka-Hyb hybrid (MLW). Days
      of test, total amount of feed consumed and valuable cuts were taken into the
      analysis to test the random distribution of the animals' phenotypic measurements
      and predicted breeding values across the contemporary groups of origin. The
      phenotypic measurements of all traits were clearly positively associated with the
      herds of origin (b = 0.52-1.08). Animals with favourable phenotypic measurements
      originated from better herds. On the contrary, the predicted breeding values
      seemed to be independent of the herd effects (b = -0.16-0.08) and suggested a
      possible random distribution across the contemporary groups.

PMID- 12498144
TI  - Percutaneous ultrasound-guided cholecystocentesis in dogs.
AB  - Percutaneous ultrasound-guided cholecystocentesis was performed on 13 healthy
      beagle dogs to determine whether percutaneous ultrasound-guided
      cholecystocentesis in the dog was a feasible and safe procedure. Clinical,
      laboratory and ultrasonographic examinations were done at 0 and 10 minutes, in
      the 2nd and 16th hour, and on the 7th day. They included a detailed physical
      examination of the mucous membranes, cardiorespiratory system and abdominal
      organs. Laboratory examinations of the blood consisted of a complete blood count,
      determination of packed cell volume (PCV), haemoglobin (Hb), total plasma protein
      (TPP), parameters of haemostasis including prothrombin time (PT), activated
      partial thromboplastin time (APTT), and enzyme activities reflecting
      hepatobiliary function, i.e. aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and gamma-glutamyltransferase (GGT). Ultrasonographic
      findings of the gallbladder (size, shape, wall, content) and appearance of the
      biliary tract and the surrounding cranial intraabdominal organs were also
      evaluated. Percutaneous ultrasound-guided cholecystocentesis was performed easily
      during the study, and dogs tolerated well the procedure performed without
      anaesthesia. All laboratory parameters of the blood remained within normal limits
      throughout the study. However, some follow-up values, i.e. PCV, TPP, APTT and
      ALT, demonstrated statistically significant differences when compared to baseline
      measurements, which might reflect the effect of 24-hour fasting before the
      experiment, as well as day-to-day metabolic fluctuations due to feeding and water
      supply during the study. There were no visible signs of bleeding from the liver,
      bile leakage from the gallbladder or accumulation of free peritoneal fluid during
      repeated ultrasonographic examinations. Percutaneous ultrasound-guided
      cholecystocentesis seems to be an important diagnostic procedure in canine
      gallbladder diseases and can be used safely and easily to gain gallbladder bile
      for diagnosis of bacterial cholecystitis or for investigating hepatobiliary
      function in the dog.

PMID- 12498145
TI  - Effects of a non-starch polysaccharidase enzyme preparation from Thermomyces
      lanuginosus on energy and protein metabolism and milk yield of dairy cattle.
AB  - Non-starch polysaccharides (NSPs) form an integral part of the cell walls in
      plants and represent considerable available energy when degraded into absorbable
      mono-, di-, tri- and oligosaccharides. The ruminal microflora hydrolyses a good
      part of NSPs, however, recently there have been attempts to enhance the rate of
      utilisation by using external polysaccharidase enzymes. In the present study the
      effects of an enzyme preparation (Rumino-Zyme) high in xylanase activity were
      studied on ruminal volatile fatty acid (VFA) concentration, parameters of energy
      and protein metabolism, milk yield, feed conversion ratio (FCR) and body
      condition score of high-yielding dairy cows. A lignolytic enzyme preparation
      produced by the thermophilic fungus Thermomyces lanuginosus was applied in the
      present experiment and fed to dairy cows at 34 g/day dosage in the period between
      calving and the 110th day of lactation. This preparation increased VFA
      concentration in the rumen from about 32 days after calving and onward. Increased
      VFA concentration was followed by an about 5 to 10% increase in milk production
      and an almost 0.1% increase in butterfat production. Increased VFA concentration
      produced more balanced energy metabolism in the experimental cows as indicated by
      the lower incidence rate of hyperketonaemia, and lower acetoacetic acid and non
      esterified fatty acid (NEFA) concentration in the blood of the experimental cows.
      Aspartate aminotransferase (AST) activity was tendentiously higher in the control
      group and the proportion of cows that had AST activity higher than 100 U/l was
      also higher in the control group. Both control and experimental cows showed
      balanced protein and acid-base metabolism throughout the experiment. Enhanced VFA
      concentration contributed to an improvement in energy balance in the experimental
      cows with a resultant improvement of feed intake and feed utilisation. Due to the
      more balanced energy metabolism postparturient body condition loss of the treated
      cows was reduced.

PMID- 12498146
TI  - Association between endometritis and urocystitis in culled sows.
AB  - Slaughterhouse sampling and examination of urogenital tracts of 499 sows and
      gilts culled for reproductive reasons from 21 Hungarian herds were performed over
      a 6-year period. The aim was to estimate the prevalence of different urogenital
      tract lesions, and to provide sensitivity and specificity estimates for
      macroscopic and bacteriological examinations in the diagnosis of urocystitis and
      endometritis. Furthermore, the association between endometritis and urocystitis
      was assessed. The prevalence of main lesions of the urogenital tract was similar
      to that reported in other studies. The 'sensitivity' of macroscopic and
      bacteriological methods was determined statistically by taking histopathology as
      the 'Gold Standard'. As a result, the 'sensitivity' of macroscopic methods for
      the diagnosis of endometritis and urocystitis was < or = 18.1% and 47.9%,
      respectively, while the 'sensitivity' of bacteriology for the diagnosis of the
      same conditions was < or = 31.8% and 63.0%, respectively. The presumed positive
      association between urocystitis and endometritis was confirmed; it was not
      confounded by parity. Animals affected by urocystitis had a 3.5 times higher odds
      to simultaneously have endometritis than animals without urocystitis.

PMID- 12498147
TI  - Somatotrophic and thyroid hormones around the onset of lay in broiler breeders
      under different conditions.
AB  - Somatotrophic and thyroid hormones were determined around the onset of
      reproduction in broiler breeders reared in two different housing systems [dark,
      close-sided house (CH) and conventional, open-sided house (OH)]. In both groups
      age-related changes were obvious for thyroxine (T4), growth hormone (GH) and
      insulin-like growth factor (IGF-1); levels of T4 decreased, especially between 24
      and 28 weeks in both groups; concomitantly GH sharply increased over the same
      period. A transient peak in triiodothyronine (T3) occurred between 25 and 27
      weeks. The effect of housing was only present after the onset of lay. Between
      weeks 27-28 and the end of the period studied, the CH group showed higher levels
      of GH and T3 but lower T4 levels as compared to the OH group. A significant
      increase in GH after onset of lay, without any significant rise in T3 or in IGF
      I, could point to a relative insensitivity to high plasma GH levels. Changes at
      GH receptor level, together with an increased pituitary GH secretion and/or
      decreased GH turnover may be expected. This may indicate that hypothalamo
      pituitary changes at the onset of lay not only imply changes of gonadotrophic
      cell function, but also other hormonal axes. The relatively decrease in T4
      without changes in T3, may point to a decrease in the activity of the thyrotropic
      axis.

PMID- 12498148
TI  - Content of retinol and retinyl esters in blood plasma, liver, kidney and
      reproductive organs of Japanese quails.
AB  - Due to its importance in many physiological processes such as cell proliferation
      and differentiation, vitamin A plays a key role in reproduction. The present
      study examines the content and distribution of retinol and retinyl esters in the
      blood plasma, liver, kidney, ovary and oviduct (infundibulum, magnum, isthmus and
      uterus) of the laying Japanese quail. (1) The results show that the stage of egg
      laying had no influence on the level of vitamin A (retinol or retinyl esters) in
      plasma, kidney and liver. (2) The results further indicate that in the oviduct
      there are quantitative and qualitative differences in the concentration of
      retinol and retinyl esters, but that these differences are not altered by the
      stage of egg formation. (3) The highest levels of vitamin A in the isthmus and
      uterus were associated with a predominance of retinyl esters (palmitate and
      stearate); sections with lower total levels of vitamin A (infundibulum, magnum)
      had retinol as the more dominant form of vitamin A. (4) Changes in the ratio of
      retinol to retinyl esters in the various sections of the avian oviduct might
      point to metabolic differences. The storage of vitamin A might therefore be the
      predominant function of the uterus and isthmus; in the infundibulum and magnum,
      where vitamin A is predominantly present as retinol, vitamin A serves rather as a
      precursor for the modulation of the cellular metabolism of these structures.

PMID- 12498149
TI  - Effect of double nursing on some anatomical and physiological properties of the
      digestive tract of rabbits between 23 and 44 days of age.
AB  - Anatomical and physiological properties of the digestive tract were examined and
      compared in young rabbits nursed either by one (SS) or by two does (DD) daily up
      to the age of 35 days. At the age of 23, 30, 37 and 44 days, 8 young per
      treatment were euthanised. Double suckling and the subsequent higher level of
      solid feed intake after weaning were found to exert a stronger influence on the
      weight of the entire gastrointestinal tract and that of its individual parts (the
      stomach, small intestine, caecum and colon) than on its length. The quantity of
      the gastric content was found to rise with advancing age in both groups (from 36
      to 70 g and from 37.5 to 79 g). In both groups the pH of the stomach was higher
      during the suckling period (4.5-5.3) than subsequent to weaning (1.6-2.4). The
      quantity of the caecal content also increased with age (from 4 or 8 g), but on
      the 37th day significantly higher quantities of caecal content were recorded in
      DD rabbits (50.5 g compared with 35 g). The pH of the caecal content decreased
      more slowly from an initial high value (6.0 and 6.5 in SS and DD rabbits,
      respectively), and by the 37th day had settled at a low value (5.7-5.8) in both
      groups. The dry matter content of the caecal content decreased from 270-273 g to
      188-207 g in both groups. Total volatile fatty acid (tVFA) and acetic acid (C2)
      concentration, which amounted to 66-88% of tVFA, rose; in SS rabbits they were at
      higher levels by the 30th day (53.6 and 42.2 mmol/L, respectively), and remained
      at an increased level until the 44th day (P < 0.05). The ratio of C3: C4 was high
      on the 23rd day (2.5 and 2.4), but dropped at the age of 30 days (0.5 in SS and
      1.7 in DD, P < 0.05) and, further, by the 37th day (0.2 in SS). In SS rabbits
      coliform count proved significantly lower (10(5)) on the 23rd day than in DD
      rabbits (10(6)). By the 37th day this count had decreased in both groups and
      subsequently remained at a low level (< 10(4)). By the 23rd day Bacteroides were
      present in large quantities (10(8)) in the caecum and showed no change with
      advancing age or feeding regime.

PMID- 12498150
TI  - Haematology and some blood chemical parameters of young carp till the age of
      three years.
AB  - Haematological and biochemical analyses of blood were performed in carp (Cyprinus
      carpio L.) kept in small ponds. Caught and anaesthetised carp were clinically
      examined and blood samples were taken at regular intervals during the three
      years. In the first year of examinations, the haemoglobin and haematocrit values
      of carp fry significantly increased (P < 0.01) from June to September. The
      intensive growth of carp in the summer period in the second year was accompanied
      by adequate erythropoiesis. During hibernation haematocrit and haemoglobin
      significantly decreased (P < 0.05) and mean corpuscular haemoglobin concentration
      (MCHC) increased (P < 0.01) in both scaly and mirror carp. MCHC increased also
      with the age and increasing body weight of the fish. Mirror carp had lower
      haematocrit and haemoglobin values than scaly carp (P < 0.01). Comparative
      haematological analyses between carp of normal and poor body condition showed
      that moderate anaemia appeared in those with poor body condition. The results
      indicate that there is marked seasonal and age-dependent variation in the values
      of haematocrit and haemoglobin. Pond water quality investigations indicated good
      environmental conditions. A 50% increase (P < 0.05) of glucose concentration was
      found from June to September in the blood plasma of carp in the third year,
      accompanied by an even more increased (80%; P < 0.01) concentration of total
      lipids. At the same time, considerable changes of cholesterol and total protein
      concentrations were not observed. The results suggest that the investigated
      haematological and biochemical variables could be successfully utilised in
      monitoring the metabolic balance and health status of fish in intensive culture.

PMID- 12498151
TI  - A simplified biopsy method for precompacted mouse embryos: a technical report.
AB  - This article presents a new, simple and rapid embryo biopsy method. The
      blastomere for genetic analysis can be separated from a precompacted mouse embryo
      after a partial zona digestion with the use of a holding pipette. For the
      micromanipulation only two microcapillaries and micromanipulators are needed. The
      development of the biopsied embryos was studied during in vitro culture and in
      utero following embryo transfer. There was no significant difference between the
      treated and the control groups in the ratio of embryos that developed to the
      blastocyst stage, although the biopsied embryos were delayed in their development
      because they contained significantly fewer cells compared to the control ones at
      the same stage. Although there was no difference in the ratio of implantation,
      the development of the biopsied embryos in utero was also delayed 12-24 hours on
      the 9th day of pregnancy. No difference in development was visible from the 13th
      day of pregnancy. Statistically, no differences were found in the developmental
      ratio (number of developed fetuses/transferred embryos) of the control and
      treated embryos during gastrulation (9th day of pregnancy), at the beginning of
      organogenesis (13th day of pregnancy) and before birth (19th day of pregnancy).
      The embryo biopsy method presented here can be a new and useful tool for
      preimplantation genetic diagnosis.

PMID- 12498152
TI  - The endosomal epsilon-coatomer protein is involved in human adenovirus type 5
      internalisation.
AB  - The effects of bafilomycin A1 and of the reduced level of endosomal epsilon-COP
      (coatomer protein) on the infectivity of human adenovirus type 5 were
      investigated in Coxsackie adenovirus receptor- (CAR-) transfected Chinese hamster
      ovary (CHO) cells. The endosomal proton pump inhibitor bafilomycin A1 was able to
      cause only partial inhibition. Using Id1F cells (an epsilon-COP thermosensitive
      mutant CHO cell line) the reduction of epsilon-COP level also had partial
      inhibitory effect. Based on these results and comparing them to existing models
      of the adenovirus entry, we propose a refined model in which there are two
      pathways of adenoviral entry: the first one involves the epsilon-COP as the
      downstream effector of the acidification and can be blocked by bafilomycin A1 and
      the second one is a pH-independent pathway.

PMID- 12498153
TI  - The HIV pharmacy: managing quality and costs of HIV care.

PMID- 12498154
TI  - Can HIV infection be treated successfully with a once-daily regimen?
AB  - Although once-daily dosing might not be appropriate for all patients, this
      schedule provides patients with a regimen that can fit more easily into their
      established routines, thereby increasing treatment adherence. Maintaining strict
      adherence is especially important in the treatment of HIV infection, because drug
      resistant variants of HIV can emerge in suboptimal treatment environments.
      Didanosine, tenofovir, efavirenz, and lamivudine are the 4 single-agent
      antiretroviral drugs currently approved for once-daily administration. The
      combination of amprenavir boosted with ritonavir was FDA-approved for once-daily
      use in February 2002. Other new antiretroviral drugs are currently in
      development, as are new dosing schedules for existing antiretroviral drugs.
      Combinations of antiretroviral drugs, especially protease inhibitors boosted with
      ritonavir, are also being studied.

PMID- 12498155
TI  - Editorial comment: once-daily antiretroviral therapy.

PMID- 12498156
TI  - Brain natriuretic peptide and HIV-related cardiomyopathy.
AB  - The brain natriuretic peptide (BNP) assay is a new, relatively inexpensive, and
      simple test that has the potential to be an early, cost-effective, and reliable
      marker for HIV-related cardiomyopathy. We report 1 case of HIV-related
      cardiomyopathy and 10 cases of of HIV infection with unknown heart disease in
      which we measured BNP levels and performed echocardiography. We found a
      significant inverse relationship between BNP and left ventricular function in
      these patients. Further basic and epidemiologic research on BNP measurement for
      the detection of HIV-related cardiomyopathy is needed to support these findings,
      which if confirmed, could have important clinical and public health implications.

PMID- 12498157
TI  - A novel family of nuclear transport receptors mediates the export of messenger
      RNA to the cytoplasm.
AB  - Fully processed mRNAs are exported to the cytoplasm where they direct protein
      synthesis. A general feature of mRNA export is that it is an active, receptor
      mediated process. The mRNA export receptors are thought to recognize and bind to
      the mRNA-export cargoes either directly or indirectly (via adaptor proteins) and
      facilitate their translocation across the central channel of the nuclear pore
      complex (NPC). On the cytoplasmic side of the NPC, the exported mRNA is released
      and the receptor returns to the nucleoplasm, without the cargo, to initiate
      additional rounds of export. Recent, studies in yeast and in higher eukaryotes
      have led to the elucidation of an evolutionarily conserved pathway for the export
      of bulk mRNA to the cytoplasm.

PMID- 12498158
TI  - To: J. Hoffstedt et al. (2002) The common -675 4G/5G polymorphism in the
      plasminogen activator inhibitor-1 gene is strongly associated with obesity.

PMID- 12498159
TI  - Conflicting results on variation in the IGFI gene highlight methodological
      considerations in the design of genetic association studies.

PMID- 12498160
TI  - Report of the 15th Annual General Meeting of the EASD European Diabetic
      Nephropathy Study Group (EDNSG) held in Barcelona, Spain 3-4 May 2002.

PMID- 12498161
TI  - Diabetes and Nutrition Study Group of the EASD (DNSG). Minutes of the General
      Assembly held at Samos on 29 June 2002. European Association for the Study of
      Diabetes.

PMID- 12498162
TI  - JAMA patient page. Quality of life.

PMID- 12498163
TI  - 7th EASD/JDRF Oxford Workshop. "New Frontiers in the Treatment and Prevention of
      Type 1 Diabetes and its Complications. Keble College, Oxford, 3-5 August 2002.
      European Association for the Study of Diabetes/Juvenile Diabetes Research
      Foundation.

PMID- 12498164
TI  - The discovery of the electric shock.

PMID- 12498165
TI  - The paucity of grants among young scientists.

PMID- 12498166
TI  - The paucity of grants among young scientists.

PMID- 12498167
TI  - The paucity of grants among young scientists.

PMID- 12498168
TI  - The paucity of grants among young scientists.

PMID- 12498170
TI  - Like it and lump it.

PMID- 12498169
TI  - Phage biology: coming of age.

PMID- 12498171
TI  - Diabetics don't get recommended care.

PMID- 12498172
TI  - New treatment offers alternative to spinal fusion surgery.

PMID- 12498173
TI  - Sexually transmitted disease guidelines focus on prevention.

PMID- 12498174
TI  - Outpatient pelvic inflammatory disease treatment as effective as inpatient care,
      study finds.

PMID- 12498175
TI  - Speciosity in the early Homo lineage: too many, too few, or just about right?

PMID- 12498176
TI  - About benign idiopathic partial epilepsies in infancy.

PMID- 12498177
TI  - Continuing to manage professional identities.

PMID- 12498178
TI  - Does MS have a future after the Nobel Prize?

PMID- 12498179
TI  - Looking at trace impurities on silicon wafers with synchrotron radiation.

PMID- 12498180
TI  - Isotopically labeled analogues for drug quantitation.

PMID- 12498181
TI  - American Society for Mass Spectrometry: evolution of a scientific society.

PMID- 12498182
TI  - Are ELSDs coming out of the shadows?

PMID- 12498184
TI  - Dual conductivity/amperometric detection system for microchip capillary
      electrophoresis.
AB  - The performance characteristics and advantages of a new dual electrochemical
      microchip detection system based on simultaneous conductivity and amperometric
      measurements are described. The system relies on the combination of a contactless
      conductivity detector with an end-column thick-film amperometric detector. Such
      coupling of the conductivity and amperometric detection modes in a single
      separation channel greatly enhances the sample characterization to offer
      simultaneous measurements of both ionic and electroactive species, improved
      reproducibility, and confirmation of peak identity. The simultaneous measurement
      of nitroaromatic and ionic explosives is used for demonstrating the ability to
      detect both electroactive and ionic species. Major improvements are also observed
      for analytes responding at both detectors. For example, the generation of dual
      response ratios can be used to improve the reproducibility and confirm the peak
      identity/integrity. Such dual response ratios reflect the distinct redox and
      conductivity properties of the individual analytes. The independence of the two
      detectors is reflected in the absence of "cross-talk" effects. The behavior of
      the dual detector is comparable with those of the individual detectors. Such a
      dual electrochemical detection system is easy to implement and requires
      inherently portable low-cost instrumentation.

PMID- 12498183
TI  - A disposable, reagentless, third-generation glucose biosensor based on
      overoxidized poly(pyrrole)/tetrathiafulvalene-tetracyanoquinodimethane composite.
AB  - A disposable glucose biosensor based on glucose oxidase immobilized on
      tetrathiafulvalene-tetracyanoquinodimethane (ITF-TCNQ) conducting organic salt
      synthesized in situ onto an overoxidized poly(pyrrole) (PPy(ox).) film is
      described. The TIF-TCNQ crystals grow through the nonconducting polypyrrole film
      (ensuring electrical connection to the underlying Pt electrode) and emerge from
      the film forming a treelike structure. The PPy(ox) film prevents the interfering
      substances from reaching the electrode surface. The sensor behavior can be
      modeled by assuming a direct reoxidation of the enzyme at the surface of the TTF
      TCNQ crystals. A heterogeneous rate constant around 10(-6) - 10(-7) cm s(-1) has
      been estimated. The biosensor is nearly oxygen- and interference-free and when
      integrated in a flow injection system displays a remarkable sensitivity (70
      nA/mM) and stability.

PMID- 12498185
TI  - Optical and electrochemical properties of optically transparent, boron-doped
      diamond thin films deposited on quartz.
AB  - The optical and electrochemical properties of transparent, boron-doped diamond
      thin film, deposited on quartz, are discussed. The films were deposited by
      microwave-assisted chemical vapor deposition, for 1-2 h, using a 0.5% CH4/H2
      source gas mixture at 45 Torr and 600 W of power. A high rate of diamond
      nucleation was achieved by mechanically scratching the quartz. This pretreatment
      leads to the formation of a continuous film, in a short period of time, which
      consists of nanometer-sized grains of diamond. The thin-film electrode was
      characterized by cyclic voltammetry, atomic force microscopy, and UV-visible
      absorption spectrophotometry. The film's electrochemical response was evaluated
      using Ru(NH3)6(3+/2+) in 1 M KCl, Fe(CN)6(3-/4-) in 1 M KCl, and chlorpromazine
      (CPZ) in 10 mM HClO4. The film exhibited a low voltammetric background current
      and a stable and active voltammetric response for all three redox systems. The
      optical transparency of the polycrystalline film in the visible region was near
      50% and fairly constant between 300 and 800 nm. The optical and electrical
      properties were extremely stable during 48-h exposure tests in various aqueous
      (HNO3, NaOH) solutions and nonaqueous (e.g., chlorinated) solvents. The
      properties were also extremely stable during anodic and cathodic potential
      cycling in harsh aqueous environments. This stability is in stark contrast to
      what was observed for an indium-doped tin oxide thin film coated on quartz. The
      spectroelectrochemical response (transmission mode) for CPZ was studied in
      detail, using a thin-layer spectroelectrochemical cell. Thin-layer voltammetry,
      potential step/ absorption measurements, and detection analytical figures of
      merit are presented. The results demonstrate that durable, stable, and optically
      transparent diamond thin films, with low electrical resistivity (approximately
      0.026 omega x cm) laterally through the film, can be deposited on quartz.

PMID- 12498186
TI  - Allele-specific genotype detection of factor V Leiden mutation from polymerase
      chain reaction amplicons based on label-free electrochemical genosensor.
AB  - An electrochemical genosensor for the genotype detection of allele-specific
      factor V Leiden mutation from PCR amplicons using the intrinsic guanine signal is
      described. The biosensor relies on the immobilization of the 21-mer inosine
      substituted oligonucleotide capture probes related to the wild-type or mutant
      type amplicons, and these probes are hybridized with their complementary DNA
      sequences at a carbon paste electrode (CPE). The extent of hybridization between
      the probe and target sequences was determined by using the oxidation signal of
      guanine in connection with differential pulse voltammetry (DPV). The guanine
      signal was monitored as a result of the specific hybridization between the probe
      and amplicon at the CPE surface. No label-binding step was necessary, and the
      appearance of the guanine signal shortened the assay time and simplified the
      detection of the factor V Leiden mutation from polymerase chain reaction (PCR)
      amplified amplicons. The discrimination between the homozygous and heterozygous
      mutations was also established by comparing the peak currents of the guanine
      signals. Numerous factors affecting the hybridization and nonspecific binding
      events were optimized to detect down to 51.14 fmol/mL target DNA. With the help
      of the appearance of the guanine signal, the yes/no system is established for the
      electrochemical detection of allele-specific mutation on factor V for the first
      time. Features of this protocol are discussed and optimized.

PMID- 12498187
TI  - Nitric oxide-releasing fluorescence-based oxygen sensing polymeric films.
AB  - The in vitro analytical performance of fluorescence-based oxygen sensing
      polymeric films prepared with silicone rubbers that spontaneously release nitric
      oxide (NO) is examined. The use of NO-release polymers for fabricating functional
      optical sensors is proposed as a potential solution to fingering biocompatibility
      and concomitant performance problems encountered with prototype intravascular
      optical oxygen sensors. Plasticized silicone rubber films formulated with two
      distinct types of diazeniumdiolate NO donors release NO for more than 24 h. The
      optical oxygen sensing films prepared by doping these NO release polymeric
      materials with oxygen indicators (pyrene/perylene donor/acceptor pair) display
      different analytical responses, as compared to controls without NO release
      capability. Nonlinear Stern-Volmer behavior is observed for single-layer NO
      release oxygen sensors owing to heterogeneous environments for the
      pyrene/perylene pair and a concomitant quenching of the fluorescence by excess
      amine sites in such films. In contrast, a dual-layer configuration using an
      underlying NO-release silicone rubber layer covered with a second polymeric layer
      containing the fluorescent indicators is shown to yield identical sensitivity and
      linearity toward oxygen as conventional non-NO-releasing oxygen sensing films,
      while still providing surface NO fluxes necessary to yield more thromboresistive
      devices.

PMID- 12498188
TI  - In vivo biocompatibility and analytical performance of intravascular amperometric
      oxygen sensors prepared with improved nitric oxide-releasing silicone rubber
      coating.
AB  - The in vivo biocompatibility and analytical performance of amperometric oxygen
      sensing catheters prepared with a new type of nitric oxide (NO)-releasing
      silicone rubber polymer (DACA/N2O2 SR) is reported. The NO-release silicone
      rubber coating contains diazeniumdiolated secondary amine sites covalently
      anchored to a dimethylsiloxane matrix. Narrow diameter (0.9 mm, o.d.) silicone
      rubber tubing coated with this polymer can be employed to construct functional
      oxygen-sensing catheters that release NO continuously at levels > 1 x 10(-10)
      mol/cm2-min for more than 20 h. In vivo evaluation of such sensors within the
      carotid and femoral arteries of swine over a 16-h time period demonstrates that
      sensors prepared with the new NO-release coating exhibit no significant platelet
      adhesion or thrombus formation, but control sensors (non-NO release) implanted
      within the same animals do show a high propensity for cell adhesion and bulk clot
      formation. Furthermore, the in vivo analytical data provided by sensors
      fabricated with NO-release coatings (N = 9) are shown to be statistically
      equivalent to PO2 levels measured in vitro on discrete samples of blood. Control
      sensors (N = 9) placed within the same animals yield average PO2 values that are
      statistically different (p < or = 0.05) (lower) from both the levels measured on
      discrete samples and those provided by the NO-release sensors over a 16-h in vivo
      monitoring period.

PMID- 12498189
TI  - Internal response correction for fluorescent whole-cell biosensors.
AB  - Whole-cell biosensors based on reporter genes are finding a variety of
      applications in analytical chemistry. Despite their ability to selectively
      recognize the analyte in a complex mixture, few applications of such sensing
      devices to real sample analysis are reported. This is mainly due to nonspecific
      effects on the biosensor response caused by components of the sample matrix and
      by environmental changes. To overcome this problem, a bacterial biosensor with an
      internal correction mechanism of the analytical response was developed by
      introducing an additional reporter gene that provides a reference signal of the
      analytical performance of the biosensor. The first reporter (GFPuv), expressed in
      response to the concentration of L-arabinose, provides the analytical signal; the
      second reporter (EYFP), constitutively expressed if a constant amount of IPTG is
      added to each sample, was used as an internal reference. By inducing the
      biosensor with varying amounts of L-arabinose and a constant amount of IPTG, it
      was possible to obtain a dose-response curve for L-arabinose, together with a
      constant production of EYFP, which allowed for a dynamic evaluation of the
      metabolic activity of the cell. When tested in nonoptimal conditions (e.g., in
      the presence of either ethanol or deoxycholic acid at toxic concentrations), the
      presence of the internal reference system corrected the analytical response due
      to nonspecific interferences.

PMID- 12498190
TI  - Effect of interfacial refractive index on optical molecular orientation
      measurements.
AB  - The sensitivity of optical molecular orientation measurements to assumptions
      regarding thin film refractive index was investigated. Specifically, the
      influence of the interfacial refractive index on second harmonic generation (SHG)
      and linear dichroism measurements made in a total internal reflection (TIR)
      geometry was probed for five distinct molecular systems. The five molecular thin
      films ranged from weakly adsorbed species in equilibrium with solution to
      covalently bound molecules. Polarization data from the two techniques were fit
      using a range of assumed interfacial refractive indices. Surprisingly, a linear
      relationship between the difference in calculated apparent orientation angle and
      the difference in solvent-prism refractive index was observed. The trend
      indicates that for a TIR geometry, the error introduced by the thin film
      refractive index is negligible when the difference in solvent and prism
      refractive indices is less than approximately 0.08. However, there are clearly
      cases, such as a glass/air interface, in which assumptions regarding the thin
      film refractive index can result in significant error in the extracted
      orientation angle.

PMID- 12498191
TI  - Identification and quantification of feathers, down, and hair of avian and
      mammalian origin using matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry.
AB  - We describe a fast method for the identification of the origin of native and
      chemically processed feathers, down, and hair and for distinguishing closely
      related species using enzyme digestion and MALDI-TOF mass spectrometry.
      Additionally we present two methods for the quantification of different
      identified bird and mammalian samples, respectively, in binary species mixtures.
      Without any prior cleaning or isolation of single proteins, enzymatical digests
      of feathers, down, and hair are performed. Fragments generated are analyzed by
      MALDI-TOF mass spectrometry, and peak groups of different selectivity are
      established for every animal species. For the identification of individual animal
      species, only unique species-specific peaks are accepted while for species
      classification of tinted or bleached hair, the group of semispecific peaks
      (SEMPs) is used. Samples from native animal species show a higher coincidence of
      digest peak masses of SEMPs than far-related species, indicating a phylogenetical
      relationship of the investigated structure proteins. Quantification of mixed
      binary avian samples is performed by identification of preweighed single feathers
      and down, followed by calculation of the gravimetric mass fractions. The
      composition of mixed binary mammalian samples is calculated from correlation of
      the quotient of the relative peak intensities or areas of these species and the
      quotient of corresponding gravimetric mass fractions. High accuracy is achieved
      by both quantification methods. The fast methods are well suited for industrial
      quality control for example.

PMID- 12498192
TI  - Quantitative study of concentration overload, peak asymmetry, and efficiency loss
      in micellar electrokinetic chromatography.
AB  - An equation is derived for the velocity of a thin zone of specific analyte
      concentration in micellar electrokinetic chromatography. The velocity varies with
      analyte concentration, because micellar solubilization changes electrical
      conductivity, micellar electrophoretic mobility, and the partitioning of anabyte
      between mobile and micellar phases. Two studies based on a weakly and a strongly
      retained neutral analyte are made to test a limiting form of the equation in
      which the first two changes are ignored. In the first study, peak asymmetries are
      characterized and plate numbers are measured in two types of experiments: one of
      fixed surfactant concentration and variable analyte concentration and one of
      fixed analyte concentration and variable surfactant concentration. In the second
      study, the isotherm describing both experiment types is measured and interpreted
      by the Langmuir model to evaluate the velocity equation. The equation of
      continuity is solved numerically for the peak profiles governed by the velocity
      equation. In all but one case, a good agreement is found between theoretical and
      experimental peak asymmetries and plate numbers in both experiment types. An
      equation is derived for the relative change of analyte velocity caused by the
      Langmuir isotherm. The change depends on the relative migration time, micellar
      saturation, and retardation factor. The predicted velocity changes correlate well
      with peak asymmetries and efficiency losses.

PMID- 12498193
TI  - Thermodynamic interpretation of retention equilibrium in reversed-phase liquid
      chromatography based on enthalpy-entropy compensation.
AB  - The fundamentals of the retention equilibrium in reversed-phase liquid
      chromatography (RPLC) are studied on the basis of enthalpy-entropy compensation
      (EEC). First, retention data were acquired and the influence of the nature of the
      compounds, organic solvent modifier, and temperature on these data was assessed.
      Then, the data were analyzed according to the four different methods proposed by
      Krug et al., and an EEC was formally established. Linear correlations were
      observed between the logarithm of the adsorption equilibrium constants under the
      different RPLC conditions, suggesting linear free energy relationships (LFERs).
      Finally, the variations of the retentions with the experimental conditions are
      shown to be quantitatively explained by a new model based on EEC. This model
      affords a comprehensive interpretation of the variations of retention originating
      from changes of either one parameter alone or several simultaneously. The slope
      and intercept of the LFER that relates two equilibrium systems are accounted for
      by the new model. The parameters of this model are the changes of enthalpy and
      entropy associated with the retention, the compensation temperatures, and the
      experimental conditions.

PMID- 12498194
TI  - Negligible depletion solid-phase microextraction with radiolabeled analytes to
      study free concentrations and protein binding: an example with [3H]estradiol.
AB  - A new method is presented that enables sensitive measurement of free
      concentrations of radiolabeled ligands. Additionally, protein binding of
      radiochemicals in complex matrixes can be determined with this new technique that
      combines negligible depletion solid-phase microextraction (nd-SPME) with liquid
      scintillation counting (LSC) as detection. [3H]Estradiol was taken as an example
      compound. Possible matrix effects of protein on fiber uptake kinetics were
      studied. No matrix effect was found, either by fouling of the fiber, or by
      changed uptake kinetics. The validity of the method was shown in the
      determination of the affinity constant (Ka) of estradiol for human serum albumin
      (HSA). The Ka was estimated at 8.9 x 10(4) M(-1), which corresponds well with
      literature values. This study shows that nd-SPME is suitable to study the free
      concentration and protein binding of [3H]estradiol. The method described in this
      paper combines the advantages of nd-SPME with the advantages of radiolabeled
      analytes, creating a timesaving, simple, and sensitive analytical tool that will
      be particularly useful in complex matrixes containing many potential
      interferences for chromatographic methods.

PMID- 12498196
TI  - Simulation of packed-bed chromatography utilizing high-resolution flow fields:
      comparison with models.
AB  - A computer simulation of a section of the interior region of a liquid
      chromatographic column is performed. The detailed fluid flow profile is provided
      from a microscopic calculation of low Reynolds number flow through a random
      packed bed of nonporous spherical particles. The fluid mechanical calculations
      are performed on a parallel processor computer utilizing the lattice Boltzmann
      technique. Convection, diffusion, and retention in this flow field are calculated
      using a stochastic-based algorithm. This computational scheme provides for the
      ability to reproduce the essential dynamics of the chromatographic process from
      the fundamental considerations of particle geometry, particle size, flow
      velocity, solute diffusion coefficient, and solute retention parameters when
      retention is utilized. The simulation data are fit to semiempirical models. The
      best agreement is found for the "coupling" model of Giddings and the four
      parameter Knox model. These models are verified over a wide range of particle
      sizes and flow velocities at both low and high velocity. The simulations appear
      to capture the essential dynamics of the chromatographic flow process for non
      dimensional flow velocities (Peclet number) less than 500. Since the same packing
      geometry is utilized for different particle size studies, the interpretation of
      the parameter estimates from these models can be extended to the physical column
      model. The simulations reported here agree very well with a number of experiments
      reported previously.

PMID- 12498195
TI  - Determination of trace isoflavone phytoestrogens in biological materials by
      capillary electrochromatography.
AB  - Capillary electrochromatography using a specialty monolithic matrix was utilized
      in developing a rapid and highly efficient separation of isoflavones in
      biological materials. Without a preconcentration technique, it is relatively easy
      to reach ppm-ppb concentrations of these compounds in soy-based foods and verify
      them structurally using a photodiode array detector. With on-column
      preconcentration, we were able to measure low-ppb levels in human serum. Using
      blood samples from human volunteers, whose diet was supplemented by a soy-based
      product, the method has been validated for high-throughput screening of
      isoflavones in clinical studies.

PMID- 12498197
TI  - In situ single-molecule detection of antibody-antigen binding by tapping-mode
      atomic force microscopy.
AB  - We performed in situ detection of specific and nonspecific binding during
      immunoreaction on surfaces at the same location before and after analyte was
      injected using tapping-mode atomic force microscopy (TM-AFM) in liquid and
      demonstrated the ability of TM-AFM to monitor the occurrence of single-molecule
      binding events and to distinguish nonspecific from specific binding by examining
      topographical change. Two antigen/antibody pairs were investigated: chorionic
      gonadotropin (hCG)/mouse monoclonal anti-hCG and goat IgG (anti-intact hCG)/
      mouse monoclonal anti-goat IgG. Antibody (or antigen) molecules were covalently
      immobilized on uniform mixed self-assembled monolayers (SAMs) terminated with
      carboxylic acid and hydroxyl groups. Mixed SAMs allow the control of the density
      of immobilized antibody (or antigen) on surfaces to achieve the detection of
      individual antigens, antibodies, and antigen/antibody complexes. This in situ TM
      AFM-based detection method allows the single-molecule detection of
      antigen/antibody binding under near-physiological environment and the distinction
      of nonspecific from specific binding. It could be extended into a microarray.

PMID- 12498198
TI  - Simulation and optimization of retention in ion chromatography using virtual
      column 2 software.
AB  - A new software package, Virtual Column 2, is described for the simulation and
      optimization of the separation of inorganic anions by ion chromatography (IC).
      The software uses a limited amount of experimental retention data acquired
      according to a correct experimental design to predict retention times for
      analytes over a designated search area of eluent compositions. The experimental
      retention data are used to solve a new retention model, called the linear solvent
      strength model, empirical approach (LSSM-EA), which then enables prediction of
      retention times for all eluent compositions in the search area. The theoretical
      development of LSSM-EA and the processes used for solving the equations are
      discussed. Virtual Column 2 can be used for eluents containing one or two
      competing ions, and the software contains retention databases for up to 33
      analytes on the Dionex AS9A-HC, AS4A-SC, and AS14A analytical columns with
      carbonate-bicarbonate eluents and the Dionex AS10, AS15, and AS16 analytical
      columns with hydroxide eluents (results for the AS10 and AS15 columns are not
      discussed in the present study). Virtual Column 2 has been evaluated extensively
      and is shown to give predicted retention times that in most cases agree with
      experimentally determined data to within 5%. The software has uses in practical
      IC method development, education and training in IC, and refinement of existing
      IC methodology. A free version of this program is available by download at
      www.virtualcolumn.com.

PMID- 12498199
TI  - Detection and resolution of intermediate species in protein folding processes
      using fluorescence and circular dichroism spectroscopies and multivariate curve
      resolution.
AB  - Thermally induced protein unfolding/folding processes have been studied on alpha
      lactalbumin and alpha-apolactalbumin. Experiments monitored by fluorescence and
      circular dichroism spectroscopic techniques on alpha-apolactalbumin showed the
      formation of an intermediate species, whereas in the case of alpha-lactalbumin,
      this intermediate species was not detected. The presence and resolution of this
      intermediate species, its spectrum, and the evolution of all conformations during
      protein unfolding/folding processes were estimated using the multivariate curve
      resolution-alternating least-squares method. Elucidation of the nature and
      contribution of the different secondary structure motifs in each of the resolved
      protein conformations, including the intermediate, was also carried out.
      Multivariate resolution has shown to be an excellent tool for the complete
      characterization of all protein conformations involved in folding processes,
      including intermediate species that cannot be isolated by physical or chemical
      means. Indeed, it is in the determination and modeling of these intermediates
      that this chemometric approach outperforms in power and reliability previous
      methodologies based on simpler measurements and data treatments and fills the
      void linked to the elucidation and interpretation of complex mechanisms in
      protein folding processes.

PMID- 12498200
TI  - Determination of platinum and rhodium in environmental matrixes by solid sampling
      electrothermal vaporization-inductively coupled plasma mass spectrometry.
AB  - Electrothermal vaporization from a graphite furnace was used in combination with
      inductively coupled plasma mass spectrometry (ICPMS) for the determination of Pt
      and Rh in environmental matrixes. Solid samples of tunnel dust, grass, and
      atmospheric aerosol collected on a cellulose filter could be analyzed directly,
      such that sample dissolution-which is not self-evident for the determination of
      platinum group metals-could be avoided. By heating the graphite furnace according
      to a multistep temperature program, spectral interferences were avoided, since a
      "dry" plasma was obtained, while "parent" ions such as Cu, Zn, and Pb, giving
      origin to interfering molecular ions, were vaporized during the thermal
      pretreatment step. For tunnel dust, the most demanding sample matrix, a mixture
      of HCl and HF was used as a modifier to stimulate the vaporization of matrix
      components during the thermal pretreatment step and, hence, to alleviate matrix
      induced analyte signal suppression during the actual vaporization step.
      Calibration was accomplished by means of single standard addition with an aqueous
      standard solution. The results obtained agreed within the experimental
      uncertainty with the corresponding reference values (certified values or results
      obtained using pneumatic nebulization ICPMS), while relative standard deviations
      of < or = 15% were typical for both Pt and Rh. In all samples, a Pt/Rh ratio of
      approximately 6-8 was established. For a typical sample mass of 2 mg, limits of
      detection were 0.35 ng/g for Pt and 0.05 ng/g for Rh.

PMID- 12498201
TI  - Optimum condition of Fourier transform infrared multiple-angle incidence
      resolution spectrometry for surface analysis.
AB  - A novel measurement technique of pure out-of-plane vibrational modes of thin
      films on a nonmetallic substrate has recently been proposed, which is named
      multiple-angle incidence resolution spectrometry (MAIRS). Since this technique
      could not be replaced by other conventional techniques, MAIRS was expected to be
      a promising tool for analysis of thin soft materials and surface adsorbates.
      Nevertheless, some experimental conditions have been found to be inappropriate
      for MAIRS, which yields incorrect results. In the present study, therefore, the
      problems in the technique have been investigated in terms of optics to improve
      the accomplishments of MAIRS. The problems have been found to have a strong
      relationship with optics in FT-IR, which is influenced by refractive index of the
      sample material and angle of incidence. In particular, optimization of the size
      matching of the detector surface and the infrared spot at the detector was a key
      to having MAIRS perform properly. It has been concluded that reliable MAIRS
      measurements require overfilling of the detector and a substrate with a high
      refractive index.

PMID- 12498202
TI  - Segmented flow injection, UV digestion, and amperometric detection for the
      determination of total cyanide in wastewater treatment plant effluents.
AB  - The currently approved method for the analysis of total cyanide (TCN) in
      wastewaters has remained virtually unchanged in the 25 years since its initial
      use; this despite its subjection to a number of interferences, many of which
      provide a positive bias in cyanide measurements, including the formation of TCN
      during sample processing and some of which remain undocumented to this day. In
      particular, many municipal wastewater treatment plant chlorinated effluents
      throughout North America have often been cited for permit violations on the
      levels of total cyanide in their effluents measured using this methodology. A
      recently developed procedure for the analysis of TCN in various matrixes that
      utilizes segmented flow injection for sample transport and reaction, on-line
      acidic UV digestion for conversion of complexed cyanide to HCN, and amperometric
      detection achieved within 4 min of sample injection is demonstrated on
      chlorinated effluents discharged from municipal wastewater treatment plants.
      Through a systematic evaluation of the chemistry of the processes involved in
      this method and an understanding of the complexity of the wastewater matrix, an
      application was developed that showed consistent reproducibility in measuring TCN
      in a variety of effluents. The method was employed initially on synthetic
      solutions containing controlled levels of constituents identified in the
      literature as interfering with the measurement of TCN through the traditional
      distillation/colorimetric approach. In its application to the analysis of TCN in
      chlorinated wastewaters, an approach was evolved that ensured that dechlorination
      carried out during sample processing did not bias the results of analysis.

PMID- 12498203
TI  - Simultaneous determination of pesticides using a four-band disposable optical
      capillary immunosensor.
AB  - The development of a four-band capillary optical immunosensor for the
      simultaneous determination of mesotrione, hexaconazole, paraquat, and diquat is
      described. Four distinct bands (each corresponding to a different analyte) are
      created in the internal walls of a plastic capillary by immobilizing protein
      conjugates of the analytes. To perform the assay, the capillary is filled with a
      mixture of anti-analyte-specific antibodies together with a standard or sample
      containing the analyte(s). After a short incubation, a mixture of the appropriate
      second antibodies labeled with fluorescein is introduced into the capillary. To
      measure the fluorescence intensity bound onto each band, the capillary was
      scanned, perpendicularly to its axis, by a laser light beam. Part of the emitted
      photons were trapped into the capillary walls and waveguided to a photomultiplier
      placed at the one end of the capillary. The analytical characteristics of the
      assays of mesotrione, paraquat, diquat, and hexaconazole were as follows:
      detection limits of 0.04, 0.06, 0.09, and 0.10 ng/mL, respectively; dynamic
      ranges up to 9, 6, 12, and 15 ng/ mL, respectively, intra- and interassay CVs
      less than 10%. The analytical characteristics of the assays were comparable with
      those of the corresponding single-analyte fluoroimmunoassays performed in
      microtitration wells, proving the ability of the proposed immunosensor for
      reliable multianalyte determinations. Moreover, the combination of low-cost
      disposable plastic capillary tubes with the low consumption of reagents, the
      short assay time, and the multianalyte feature of the proposed immunosensor
      indicates its potential for environmental analysis.

PMID- 12498204
TI  - High-basicity determination in mixed water-alcohol solutions by a dual optical
      sensor approach.
AB  - The activity of NaOH is known to be significantly affected by the presence of an
      alcohol in aqueous solutions. A novel linear relationship between
      (deltaA/deltaC(alcohol)) and C(base) was found in the highly alkaline, mixed H2O
      ROH solutions (R = Me, Et, i-Pr). The use of this linear relationship led to a
      dual-transducer approach to decompose the optical signals of optical base sensors
      and to give base and alcohol concentrations in concentrated NaOH-H2O-ROH
      solutions ([OH-] = 0.05-3.6 M). The scope of the new dual-sensor approach was
      evaluated, and errors in C(base) and C(alcohol) were analyzed. The optical base
      sensors consist of sol-gel SiO2-ZrO2-organic polymer composites doped with high
      pKa indicators. The pKa(s) of the indicators encapsulated in the composite films
      were determined and found to be affected by the composition of the sol-gel
      composites. Optical sensors and their uses in multicomponent systems are of
      intense current interest.( 1-7) In the multicomponent systems, the activity of
      the analyte and sensor response are often affected by change in ionic strength.
      For optical sensors that are based on indicator equilibria involving the analyte
      as their transducing mechanism, such effect is particularly significant. The
      concentrations of both the analyte and other chemicals affect ionic strength, and
      the sensor response to concentration of the analyte is thus often
      indistinguishable from those of other chemicals. An accurate measurement of each
      component in these multicomponent systems is actively studied. Several approaches
      have been developed to correct ionic strength in optical sensing for the pH
      region and solutions of low-to-medium ionic strength. (1-9) We recently reported
      a dual-transducer approach to measure acid concentrations (2-9 M HCl) in salt
      containing, concentrated strong acids such as MClx-HCl (M = Li, Ca, Al)
      solutions. (10) This approach was shown to reduce the error in C(acid) from, for
      example,

PMID- 12498205
TI  - Hydrophobic, pellicular, monolithic capillary columns based on cross-linked
      polynorbornene for biopolymer separations.
AB  - Monolithic capillary columns were prepared by transition metal-catalyzed ring
      opening metathesis copolymerization of norborn-2-ene and 1,4,4a,5,8,8a-hexahydro
      1,4,5,8-exo,endo-dimethanonaphthalene inside a silanized 200-microm-i.d. fused
      silica capillary using a mixture of toluene and 2-propanol as porogen and
      Cl2(PCy3)2Ru(=CHPh) as initiator. The synthesized columns allowed the rapid and
      highly efficient separation of single- and double-stranded nucleic acids by ion
      pair reversed-phase high-performance liquid chromatography and of proteins by
      reversed-phase high-performance liquid chromatography. Compared to 3-mm-i.d.
      analytical columns synthesized from an identical polymerization mixture, a
      considerable improvement in the peak widths at half-height of oligonucleotides in
      the order of 60-80% was obtained. Significant differences in morphology between
      the capillary column, where the surface of the monolith was rather soft and
      rugulose, and the analytical column, where the surface was very sharp and smooth,
      were observed, most probably due to differences in polymerization kinetics. The
      synthesized monoliths were successfully applied to the separation of the
      diastereomers of phosphorothioate oligodeoxynucleotides. To confirm the identity
      of the eluting compounds on the basis of their intact molecular masses, the
      chromatographic separation system was on-line hyphenated to electrospray
      ionization mass spectrometry.

PMID- 12498206
TI  - Small-scale analysis of O-linked oligosaccharides from glycoproteins and mucins
      separated by gel electrophoresis.
AB  - A technique with subpicomolar sensitivity was developed for analyzing O-linked
      oligosaccharides released from glycoproteins separated by gel electrophoresis.
      The protocol involves gel electrophoresis, electroblotting to poly-(vinylidene
      fluoride) membrane, reductive beta-elimination, and analysis of released
      oligosaccharides by liquid chromatography coupled to negative ion electrospray
      mass spectrometry. It was also found that N-linked oligosaccharides could be
      recovered under the same conditions, found both as free oligosaccharides and as
      distinct glycopeptides created from reductive cleavage of the protein backbone,
      giving some information on site-specific glycosylation. The method was used to
      demonstrate that the difference between human alpha-2HS-glycoprotein isoforms
      separated by 2D-gel electrophoresis was partially due to sialylation of both O
      linked and N-linked oligosaccharides. It was also shown that both acidic and
      neutral oligosaccharides could be recovered and analyzed simultaneously from high
      molecular mass (200,000-5,000,000 Da) highly glycosylated mucin glycoproteins
      collected from small intestine and saliva and separated by sodium dodecyl sulfate
      agarose/polyacrylamide composite gels. Mass spectrometric data not only gave
      information about the mass distribution of the heterogeneous mixtures of
      oligosaccharides from [M - xH](x-) ions but also gave information about the
      isomeric heterogeneity of the oligosaccharides from their resolution by porous
      graphitized carbon chromatography. Tandem mass spectrometry was explored as a
      technique for distinguishing between oligosaccharide isomers with different
      sequences and also between oligosaccharides with the same sequence but with
      different linkage configurations.

PMID- 12498207
TI  - Oxygen isotopic measurements by secondary ion mass spectrometry in uranium oxide
      microparticles: a nuclear forensic diagnostic.
AB  - To exploit oxygen isotopic measurement by SIMS as a diagnostic tool in nuclear
      forensics, the magnitude and reproducibility of 0-isotope instrumental mass
      discrimination for O-isotope standards in the SIMS laboratory at the Institute
      for Transuranium Elements has been evaluated. Tests for matrix-dependent
      discrimination effects on three different O-isotope standards with substantially
      different matrix compositions have been performed. The results were checked by an
      interlaboratory comparison of O-isotope discrimination with those obtained in the
      SIMS laboratory at the Lawrence Livermore National Laboratory on two standards.
      The results from the two laboratories are in very good agreement, indicating
      statistically indistinguishable instrumental mass discrimination factors for
      180/160 ratios on the Cameca 6f and 3f, when the analyses are performed under the
      experimental conditions described. The 2sigma(mean) uncertainties of these
      factors are in the range of 0.3-0.9%. In accordance with the tested methodology,
      0-isotope compositions were measured in three particulate uranium oxide samples
      of nuclear forensics interest.

PMID- 12498208
TI  - Room-temperature isopiestic distillation of in situ generated arsenious chloride
      and its application for the determination of trace level impurities in arsenious
      oxide.
AB  - The room-temperature vapor pressures of HCl and AsCl3 in the presence of
      hydrochloric acid have been utilized in situ for the removal of arsenious oxide
      matrix as AsCl3 by isopiestic distillation. Reagent purification, sample
      dissolution, and matrix separation have been carried out in one step with a clean
      environment for both analyte and analyst. Quantitative recoveries have been
      achieved for most of the elements including volatile elements. Blank levels were
      found to be in nanograms per gram of As2O3 despite use of common reagents and
      simple reaction vessel. The utility of the present method for the analysis of
      As2O3 samples has been demonstrated.

PMID- 12498209
TI  - Application of an absorption-based surface plasmon resonance principle to the
      development of SPR ammonium ion and enzyme sensors.
AB  - Two new types of surface plasmon resonance (SPR) sensors that can determine the
      concentration of ammonium cations and urea were realized based on the previously
      reported theory of the absorption-based SPR measurement method. The change of the
      dielectric constant caused by the change of the light absorption characteristics
      of dyes incorporated in a sensing membrane phase is utilized in these SPR
      sensors. The determination of ions using the SPR sensor was realized by detecting
      the SPR signals of the minimum reflectance related to the change of absorption
      spectra of the dye in the ion optode membrane consisting of an ammonium-selective
      ionophore (TD19C6) and a lipophilic cationic dye (KD-M11) that shows absorption
      spectral changes due to protonation and deprotonation. A SPR enzyme sensor that
      can determine the concentration of urea was prepared by the combination of this
      ion optode membrane and an enzyme membrane based on urease. With the newly
      developed SPR sensors, the intensity changes of the reflectance at the fixed SPR
      resonance angle are monitored, which is different from conventional SPR sensors
      where usually the change of the SPR resonance angles is detected. In a continuous
      flow experiment using the SPR ion sensor for NH4+ ion determination, a dynamic
      measurement range from 10(-5) to 10(-2) M was achieved. In the case of the enzyme
      based SPR urea sensor, a dynamic range from 10(-4) to 10(-1) M was observed in a
      stopped-flow batch arrangement. It is expected that this sensing technique can be
      applied for the SPR-based detection of a wide range of low molecular weight
      analytes.

PMID- 12498210
TI  - Quantitation of manganese by use of an electron spin resonance method.
AB  - An electron spin resonance (ESR) measurement is described for the quantitation of
      manganese in biological materials. The content of Mn was measured at room
      temperature by using 5 microL of a solution of the tissue wet-ashed with HNO3. In
      the ESR spectrum, Mn(H2O)6(2+) showed the characteristic six lines, and
      interferences were not detected from other substances in the tissues. For these
      tissue samples, good agreement was obtained between the values obtained by the
      present method and those obtained by conventional flame atomic absorption
      spectroscopy. The concentrations of Mn in urine, blood, and most tissues were so
      low that enrichment of Mn by coprecipitation with ZnS was applied for these
      samples. It took, however, only 5 min to quantify Mn in 1 mL of urine.

PMID- 12498211
TI  - Nine-analyte detection using an array-based biosensor.
AB  - A fluorescence-based multianalyte immunosensor has been developed for
      simultaneous analysis of multiple samples. While the standard 6 x 6 format of the
      array sensor has been used to analyze six samples for six different analytes,
      this same format has the potential to allow a single sample to be tested for 36
      different agents. The method described herein demonstrates proof of principle
      that the number of analytes detectable using a single array can be increased
      simply by using complementary mixtures of capture and tracer antibodies. Mixtures
      were optimized to allow detection of closely related analytes without significant
      cross-reactivity. Following this facile modification of patterning and assay
      procedures, the following nine targets could be detected in a single 3 x 3 array:
      Staphylococcal enterotoxin B, ricin, cholera toxin, Bacillus anthracis Sterne,
      Bacillus globigii, Francisella tularensis LVS, Yersiniapestis F1 antigen, MS2
      coliphage, and Salmonella typhimurium. This work maximizes the efficiency and
      utility of the described array technology, increasing only reagent usage and
      cost; production and fabrication costs are not affected.

PMID- 12498212
TI  - Measurements of chemical warfare agent degradation products using an
      electrophoresis microchip with contactless conductivity detector.
AB  - This paper reports on a microfluidic device for the screening of
      organophosphonate nerve agent degradation products. The miniaturized system
      relies on an efficient chip-based separation of alkyl methylphosphonic acids
      (breakdown products of Sarin, Soman, and VX nerve agents) followed by their
      sensitive contactless conductivity detection. Experimental parameters relevant to
      the separation and detection processes have been optimized to yield high
      sensitivity (with 48-86 microg L(-1) detection limits), fast response (50 s for a
      three alkyl methylphosphonic acid mixture), high precision (RSD = 3.8-5.0%), and
      good linearity (over the 0.3-100 mg L(-1) range). Applicability to natural
      (river) water samples is demonstrated. The new microsystem offers promise for
      monitoring degradation products of chemical warfare agents, with advantages of
      speed/warning, efficiency, portability, sample size, and cost compared to
      conventional ion chromatography or capillary electrophoresis systems.

PMID- 12498213
TI  - Photoelectrochemical oxygen sensor using copper-plated screen-printed carbon
      electrodes.
AB  - We report here an efficient photocatalytic amperometric sensor for the
      determination of dissolved oxygen (DO) in phosphate buffer solution using a
      disposable copper-plated screen-printed carbon electrode (CuSPE). The
      photoelectrochemical activity toward DO of the CuSPE was related to the formation
      of a p-type semiconductor Cu(I)2O. The solution pH and biased potential (E(bias))
      were systematically optimized as pH 8 PBS and -0.7 V vs Ag/AgCl, respectively.
      Under optimized conditions, the calibration plot was linear in the range of 1-8
      ppm with sensitivity and regression coefficient of 23.51 (microA cm2)(-1) ppm(-1)
      and 0.9982, respectively. The reproducibility of the system was good with seven
      successive measurements of DO yielding a RSD value of 1.87%. Real sample assays
      for groundwater and tap water were also consistent with those measured by a
      commercial DO meter. The principle used in DO measurement has an opportunity to
      extend into various research fields.

PMID- 12498214
TI  - Nitrite reduction by a mixed culture under conditions relevant to shortcut
      biological nitrogen removal.
AB  - Dissimilative reduction of nitrite by nitrite-acclimated cells was investigated
      in a batch reactor under various environmental conditions that can be encountered
      in shortcut biological nitrogen removal (SBNR: ammonia to nitrite and nitrite to
      nitrogen gas). The maximum specific nitrite reduction rate was as much as 4.3
      times faster than the rate of nitrate reduction when individually tested, but the
      reaction was inhibited in the presence of nitrate when the initial nitrate
      concentration was greater than approximately 25 mg-N/1 or the initial NO3(
      )N/NO2(-)-N ratio was larger than 0.5. Nitrite reduction was also inhibited by
      nitrite itself when the concentration was higher than that to which the cells had
      been acclimated. Therefore, it was desirable to avoid excessively high nitrite
      and nitrate concentrations in a denitrification reactor. Nitrite reduction,
      however, was not affected by an alkaline pH (in the range of 7-9) or a high
      concentration of FA (in the range of 16-39 mg/l), which can be common in SBNR
      processes. The chemical oxygen demand (COD) requirement for nitrite reduction was
      approximately 22-38% lower than that for nitrate reduction, demonstrating that
      the SBNR process can be economical. The specific consumption, measured as the
      ratio of COD consumed to nitrogen removed, was affected by the availability of
      COD and the physiological state of the cells. The ratio increased when the cells
      grew rapidly and were storing carbon and electrons.

PMID- 12498215
TI  - Evaluation of methods to predict bacterial yield using thermodynamics.
AB  - Thermodynamic models can be used to predict bacterial yields and develop
      stoichiometric representation of biological reactions in the absence of empirical
      data. Several methods have been used by microbiologists, biotechnologists, and
      environmental engineers. This manuscript illustrates that these formulations are
      related. Yields predicted by estimation of Gibbs energy of dissipation and yields
      predicted by assumed efficiency of energy capture are comparable. Direct
      comparison of yield predictions from different methods shows the effects of
      assumptions inherent in the methodologies. Mathematical relationships between
      estimated values from the different methods help identify the best predictions
      from each method to bound the estimate of bacterial yield.

PMID- 12498216
TI  - Biosorption and solubilization of copper oxychloride fungicide by Aspergillus
      niger and the influence of calcium.
AB  - The biosorption of copper oxychloride fungicide particulates (approximately 1
      microm diameter), at concentrations ranging from 25 to 500 ppm active ingredient
      (ai), by pelleted mycelium of Aspergillus niger grown on Czapek Dox medium was
      evaluated. The concentration of the fungicide adsorbed to the mycelium, remaining
      suspended or solubilized in the medium, was determined by analysis of its copper
      content (CuF) using atomic absorption spectrophotometry (AAS). 2-day-old pellets
      exhibited high biosorption efficiency ranging from 97 +/- 1.0 to 88 +/- 1.2% of
      the initially added fungicide concentrations, respectively, within 10 min.
      However, under the same conditions, amounts of the removed fungicide by 6-day-old
      mycelial pellets were significantly lower and ranged from 0.5 +/- 0.03 to 0.15 +/
      0.01%. Scanning electron microscopy studies of 2-day-old pellets supplemented
      with the fungicide revealed predominant aggregations of clumps and dense
      particulates on the hyphal tips. The adsorbed CuF of 125 ppm ai fungicide
      subsequently decreased from 7.5 +/- 0.5 to 2.1 +/- 0.1 micromol Cu (mg dry wt)(
      1) after 12 h incubation. Simultaneously, the soluble portion of CuF remaining in
      the medium increased from 0.9 +/- 0.6 to 4.9 +/- 0.2 micromol Cu ml(-1). The
      presence of 50 mM CaCl2 resulted in a decrease of the adsorbed CuF to 3.5 +/- 0.5
      micromol Cu (mg dry wt)(-1) and solubilized copper in the medium increased to 5.9
      +/- 0.8 micro mol Cu ml(-1). Additionally, the cellular copper contents attained
      after 2 h were 0.08 +/- 0.01 and 0.16 +/- 0.007 micromol Cu (mg dry wt)(-1) in
      absence and presence of calcium, respectively. The addition of calcium to glucose
      starved pellets greatly increased the medium [H+] which was conclusively
      discussed in relation to Ca2+/H+ exchange capacity of the fungal cells. These
      results are of potential environmental, biotechnological and agricultural
      importance.

PMID- 12498217
TI  - Inhibition of the anaerobic digestion process by linear alkylbenzene sulfonates.
AB  - Linear Alkylbenzene Sulfonates (LAS) are the most widely used synthetic anionic
      surfactants. They are anthropogenic, toxic compounds and are found in the primary
      sludge generated in municipal wastewater treatment plants. Primary sludge is
      usually stabilized anaerobically and therefore it is important to investigate the
      effect of these xenobiotic compounds on an anaerobic environment. The inhibitory
      effect of Linear Alkylbenzene Sulfonates (LAS) on the acetogenic and methanogenic
      step of the anaerobic digestion process was studied. LAS inhibit both
      acetogenesis from propionate and methanogenesis from acetate and hydrogen and it
      is shown that the propionateutilising bacteria are more sensitive to the presence
      of LAS than the acetoclastic methanogens. It has been proven that the inhibition
      intensity depends on the solids concentration and thus the term "biomass specific
      LAS concentration" has been introduced in order to describe the phenomenon
      better. Conclusively, it is believed that the inhibitory effect of LAS is the
      main reason that anaerobic microbial enrichments on LAS have not been succeeded
      yet. Also, the inhibition caused by LAS on the acetogenic and methanogenic step
      of the anaerobic digestion process should be seriously taken into consideration
      when wastewater from a surfactant producing industry is to be treated
      biologically or enter a municipal wastewater treatment plant that employs
      anaerobic technology. The upper allowable biomass specific LAS concentration
      should be 14 mg LAS (gVSS)(-1).

PMID- 12498218
TI  - Enrichment of microbial cultures able to degrade 1,3-dichloro-2-propanol: a
      comparison between batch and continuous methods.
AB  - Microbial cultures able to degrade xenobiotic compounds are the key element for
      biological treatment of waste effluents and are obtained from enrichment
      processes. In this study, two common enrichment methods, suspension batch and
      immobilized continuous, were compared. The main selection factor was the presence
      of 1,3-dichloro-2-propanol (1,3-DCP) as the single carbon source. Both methods
      have successfully enriched microbial consortia able to degrade 1,3-DCP. When
      tested in batch culture, the degradation rates of 1,3-DCP by the two consortia
      were different, with the consortia obtained by batch enrichment presenting
      slightly higher rates. A preliminary morphological and biochemical analysis of
      the predominant colonial types present in each degrading consortia revealed the
      presence of different constituting strains. Three bacterial isolates capable of
      degrading 1,3-DCP as single strains were obtained from the batch enrichments.
      These strains were classified by 16S rRNA analysis as belonging to the
      Rhizobiaceae group. Degradation rates of 1,3-DCP were lower when single species
      were used, reaching 45 mg 1(-1) d(-1), as compared to 74 mg 1(-1) d(-1) of the
      consortia enriched on the batch method. Mutualistic interactions may explain the
      better performance of the enriched consortia.

PMID- 12498219
TI  - Clinicopathologic relevance of apoptotic and proliferative factors in human lung
      adenocarcinoma: Fas expression correlates with the histologic subtype, but not
      with the degree of apoptosis.
AB  - We immunohistochemically examined 141 surgically resected peripheral lung
      adenocarcinomas for the expression of Fas, single stranded (ss-) DNA and Ki-67,
      and statistically evaluated the relationship of these parameters with other
      clinicopathologic variables, including clinical stage, nodal involvement, and
      histopathologic subtypes classified according to WHO criteria. Fas expression by
      cancer cells was characteristically localized in the cytoplasm, and the extent of
      expression correlated well with the degree of Ki-67 reactivity (p = 0.0004), but
      not with the degree of apoptic occurrence, as assessed by ss-DNA reactivity.
      Cancer cells of the bronchioloalveolar carcinoma (BAC) subtype without invasive
      growth exhibited a significantly lower Fas expression than those of other
      subtypes (p < 0.0001). Positive expression of Fas was frequently associated with
      a high incidence of nodal involvement and advanced clinical stage, as compared
      with cases of negative expression (p = 0.0111 and p = 0.0439, respectively).
      Multivariate analysis revealed that Fas expression significantly correlated with
      the histologic subtype, but not with tumor size, nodal involvement, or clinical
      stage. Survival analysis determined by the log-rank test revealed that clinical
      stage and Ki-67 reactivity were poor prognostic variables, and Fas expression was
      not statistically significant. Based on these data, intracytoplasmic expression
      of Fas in cancer cells may participate in the development of resistance to fas
      mediated apoptosis.

PMID- 12498220
TI  - Identification of isolated and early prostatic adenocarcinoma in radical
      prostatectomy specimens with correlation to biopsy cores: clinical and
      pathogenetic significance.
AB  - Prostatic adenocarcinoma (PAC) is a multifocal disease. In this study, we
      identified isolated and small foci of PAC (ISPAC) in radical prostatectomy
      specimens, described the histopathologic features, investigated their zonal
      distribution in the prostate and their relationship with large tumor nodules, and
      correlated the findings with those of preceding biopsy cores. One hundred and
      thirty radical prostatectomy specimens performed for PAC or for urothelial
      carcinoma of the urinary bladder with incidental PAC were reviewed for
      identification of ISPAC. Prostates were serially sectioned in the horizontal
      plane and submitted in toto for microscopic examination. ISPAC were defined as
      foci of PAC measuring less than 3 mm in maximum diameter. There were 461 ISPAC
      identified in 114 cases. They were distributed in the transitional zone (TZ) (18
      foci), the apex (73 foci), the anterior horn of the non-TZ (NTZ) (118 foci), the
      base (8 foci), and the remaining NTZ (244 foci). ISPAC usually consisted of
      groups of small acini with a GS ranging from 2 to 7 (3 + 4). GSs of ISPAC
      consisted of single grade or two consecutive grades equal to or lower than those
      of the main PAC. ISPAC were more often located in close proximity to large tumor
      nodules. The number of ISPAC increased with the tumor volume up to 3 cm3, then
      decreased as the PAC became more extensive (p value = 0.02, statistically
      significant). Prostates with NTZ PAC <1.5 cm3 and TZ PAC or prostates containing
      4 or more than 4 ISPAC tended to be frequently associated with small foci of PAC
      in biopsy cores In this study, we identified ISPAC that likely represent foci of
      PAC in early development and account for the multicentricity and heterogeneity of
      PAC. ISPAC in the NTZ were common and may account for small foci of PAC or atypia
      in biopsy cores. Although these small foci of PAC or atypia in biopsy cores
      without accompanying higher GS PAC were often associated with significant PAC,
      they may also occasionally represent insignificant or vanishing PAC in subsequent
      radical prostatectomies.

PMID- 12498221
TI  - Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with
      clinicopathologic parameters and prognosis.
AB  - The aim of this study was to investigate the relationship between MUC1 and MUC2
      mucin expressions and clinicopathologic variables in gastric carcinomas with
      regard to survival times. MUC1 and MUC2 expressions were revealed
      immunohistochemically in 143 gastric carcinomas. Of these 143 patients, follow-up
      data were available for 45 (median survival time of 30 months, ranging from 2 to
      80 months). MUC1 was detected in 82 (58%), and MUC2 in 60 (42%) out of 143 cases.
      Papillary adenocarcinomas showed significantly higher MUC1 and MUC2
      immunoreactivity than did signet-ring cell and mucinous tumors (p = 0.045 and p =
      0.01, respectively). MUC1 was highly positive in intestinal-type carcinomas (p =
      0.006), whereas intestinal and diffuse carcinomas did not differ in MUC2
      expression. There was a positive correlation between tumor differentiation and
      MUC1 expression. However, no correlation was found between MUC1 and MUC2
      expressions and angiolymphatic invasion. According to the TNM classification,
      stage 1A tumors have significantly lower rates of MUC1 reactivity compared to
      higher stages (p = 0.04). The patients with gastric carcinomas expressing MUC1
      showed significantly poorer survival than those without MUC1 expression (p =
      0.04). The present study suggests that MUC1 expression be a useful prognostic
      factor for predicting the outcome of gastric carcinoma patients, whereas the role
      of MUC2 expression is still unclear.

PMID- 12498222
TI  - Histopathology of candidal hyperplastic lesions of the larynx.
AB  - Candidiasis of the larynx is rare, and candidal involvement of the larynx mostly
      occurs after pulmonary, pharyngeal and esophageal candidiasis, or as part of
      disseminated disease. We here report our morphologic observations made in five
      cases of laryngeal candidiasis. These cases had the following morphologic
      features in common: 1. pronounced epithelial hyperplasia, which may show a
      verrucous pattern, 2. prominent ortho-parakeratosis, and 3. predominantly
      neutrophilic infiltration located in the upper layers of the mucosal epithelium.
      Our morphologic observations were similar to the morphologic changes encountered
      in chronic hyperplastic candidosis of the oral mucosa. As this type of candidal
      lesions contains fewer hyphae than the usual thrush, fungal infection may be
      easily overlooked. Pronounced epithelial hyperplasia and prominent ortho
      parakeratosis may mimic squamous cell and verrucous carcinomas. In conclusion, we
      suggest performing special stains for fungi of laryngeal biopsies that have the
      morphologic features mentioned above. In that way, it is possible to detect a
      candidal infection, keeping in mind that the fungal organisms may be very few in
      number and morphologically distorted.

PMID- 12498223
TI  - Digital imaging and electronic patient records in pathology using an integrated
      department information system with PACS.
AB  - Picture archiving and communication systems have been widely used in radiology
      thus far. Owing to the progress made in digital photo technology, their use in
      medicine opens up further opportunities. In the field of pathology, digital
      imaging offers new possiblities for the documentation of macroscopic and
      microscopic findings. Digital imaging has the advantage that the data is
      permanently and readily available, independent of conventional archives. In the
      past, PACS was a separate entity. Meanwhile, however, PACS has been integrated in
      DIS, the department information system, which was also run separately in former
      times. The combination of these two systems makes the administration of patient
      data, findings and images easier. Moreover, thanks to the introduction of special
      communication standards, a data exchange between different department information
      systems and hospital information systems (HIS) is possible. This provides the
      basis for a communication platform in medicine, constituting an electronic
      patient record (EPR) that permits an interdisciplinary treatment of patients by
      providing data of findings and images from clinics treating the same patient. As
      the pathologic diagnosis represents a central and often therapy-determining
      component, it is of utmost importance to add pathologic diagnoses to the EPR.
      Furthermore, the pathologist's work is considerably facilitated when he is able
      to retrieve additional data from the patient file. In this article, we describe
      our experience gained with the combined PACS and DIS systems recently installed
      at the Department of Pathology, University of Magdeburg. Moreover, we evaluate
      the current situation and future prospects for PACS in pathology.

PMID- 12498224
TI  - Primary pulmonary low-grade marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue type with prominent hyalinosis. A case report.
AB  - We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of
      the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which
      morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory
      pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a
      history of Sjogren's syndrome and primary biliary cirrhosis, presented with a
      lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is
      characterized by dense bundles of collagen with scattered plasma cells, mature
      small lymphocytes, and histiocytes among the collagen bundles. Only the
      peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid
      infiltrates. A few centrocyte-like cells were obscured by the numerous plasma
      cells and plasmacytoid cells. In addition, lymphoepithelial lesions and
      colonalized lymphoid follicles were identified by immunohistochemistry alone.
      Although PHG and IPT are unlikely to be confused with pulmonary MALT-type
      lymphomas, the present case suggests that MALT-type lymphoma should be added to
      the list of differential diagnoses for PHG and IPT.

PMID- 12498225
TI  - Coxsackie B3 myocarditis in 4 cases of suspected sudden infant death syndrome:
      diagnosis by immunohistochemical and molecular-pathologic investigations.
AB  - Immunohistochemical and molecular-pathologic techniques have improved the
      diagnosis of myocarditis as compared with conventional histologic staining
      methods done according to the Dallas criteria. Most investigations were carried
      out on adults, and only a few authors investigating childhood deaths applied
      these modern methods, used for diagnosing myocarditis. We report on four children
      under one year of age, who suddenly died without prodromal symptoms. Their deaths
      were attributed to SIDS (sudden infant death syndrome). Immunohistochemical (LCA,
      CD68, CD45R0, MHC-class-II-molecules, VP1-capsid-protein of enteroviruses) and
      molecular-pathologic (RT-PCR) investigations, however, suggested that death was
      caused by a coxsackie-B3-myocarditis. In the future, these methods should be used
      for investigating cases with suspicion of SIDS.

PMID- 12498226
TI  - Squamous cell carcinoma arising in a hepatic forgut cyst.
AB  - We report the second case of squamous cell carcinoma arising in a hepatic foregut
      cyst (CHFC) in a 40-year-old woman. Microscopically, the lining of the cyst was
      composed of ciliated columnar epithelium, gastric and squamous epithelium. The
      squamous epithelium showed areas with dysplastic changes and other areas with
      carcinomatous transformation. In this congenital lesion, it was not surprising to
      find squamous and gastric mucosa because oesophagus, stomach, and tracheobronchic
      tree derive from the embryologic foregut. Squamous carcinoma might develop in a
      context of inflammation as in biliary cyst. In agreement with the first case
      described in the literature, this report also suggests that a large-sized
      symptomatic hepatic cyst should be excised.

PMID- 12498227
TI  - Heparan sulphate proteoglycan in scleromyxedema promotes FGF-2 activity.
AB  - The cause of progressive dermal sclerosis, proliferation of fibroblasts, and
      collagen deposition in scleromyxedema is unknown. We analyzed the heparan
      sulphate proteoglycans (HSPG) in cutaneous nodules from a patient with
      scleromyxedema in order to ascertain their role in the binding of fibroblast
      growth factor (FGF) and promoting signaling complex assembly. Total heparan
      sulphate (HS) was detected with a monoclonal antibody to HSPG on paraffin
      sections. Binding of FGF to HS was assessed using FGF-2 followed by anti-FGF-2
      antibody. The formation of HS-mediated signaling complex was studied using
      soluble FR1-AP, which contains the extracellular domain of FGF receptor-1 linked
      to alkaline phosphatase (AP) and monoclonal anti-AP-antibody. Anti FGF-2 and anti
      AP antibodies were visualized using the DAKO Envision Plus system. The dermal
      nodule of scleromyxedema contained ample HS and these bound FGF-2 and FR1-AP.
      Specificity was confirmed by prior incubation with heparitinase (no staining) and
      omission of FGF-2 (no staining). Increased amounts of HSPG were present in the
      dermal nodules of scleromyxedema compared to adjacent normal dermis and these
      bound FGF-2, immobilized the soluble receptor protein FGFR-1 and, therefore,
      formed a ternary complex composed of HSPG, FGF-2 and FGFR-1 in vitro. Since this
      complex resembles the signaling complex formed on live cells, HSPG in the nodules
      of scleromyxedema are in a configuration that promotes FGF activity.

PMID- 12498228
TI  - Novel surface modification of polymer-based separation media controlling
      separation selectivity, retentivity and generation of electroosmotic flow.
AB  - Uniformly sized packing materials based on synthetic polymer particles for high
      performance liquid chromatography (HPLC) and capillary electrochromatography
      (CEC) have been prepared from polymerization mixtures containing methacrylic acid
      (MAA) as a functional monomer and by using a novel surface modification method.
      This "dispersion method" affords effectively modified separation media. Both the
      amount of MAA utilized in the preparation and reaction time affect the
      selectivity of chromatographic separation in both the HPLC and the CEC mode and
      electroosmotic flow. This detailed study revealed that the dispersion method
      effectively modified internal surface of macroporous separation media and, based
      on the amount of MAA introduced, exclusion mechanism for the separation of
      certain solutes could be observed.

PMID- 12498229
TI  - Sample matrix influence on the choice of background electrolyte for the analysis
      of bases with capillary zone electrophoresis.
AB  - Low levels of impurities need to be determined in drugs. Consequently, if UV
      detection is used, a large sample amount must be loaded and as narrow peaks as
      possible obtained. The sample matrix and the stability of the samples as well as
      the peak resolution should be considered when the electrolyte is chosen. In this
      study the influence of the sample matrix composition with varying background
      electrolytes on the peak appearance of model mixtures loaded in large amounts was
      investigated. A robust electrolyte for analysis of bases in a sample with varying
      pH was found to consist of a buffering co-ion and a buffering counter-ion (the pH
      was approximately 4.2 in the electrolyte). If a minor component has higher
      mobility than the macrocomponent and the co-ion, better peak shape can be
      obtained if, for instance, enough sodium chloride is added to the sample, i.e.,
      sample self-stacking is exploited. The effect of addition of organic modifiers,
      isopropanol or acetonitrile, was examined and good linearity and precision have
      been shown for impurities in the concentration range tested, approximately 0.03
      to 5 mol% of the main component, in model mixtures.

PMID- 12498231
TI  - Sub-second liquid chromatographic separations by means of shear-driven
      chromatography.
AB  - Utilizing the concept of shear-driven chromatography, we have been able to
      realize reversed-phase LC separations in flat rectangular nano-channels coated
      with a C8 monolayer and being as thin as 100 nm. At this scale, the separation
      kinetics are strongly enhanced, as is witnessed by the extremely short time (<
      0.1 s) needed to separate a mixture of coumarin dyes. The observed plate numbers
      are still relatively small, because the experiments were conducted in ultra-short
      columns (< or = 1 mm) and under injection band width-limiting conditions.

PMID- 12498230
TI  - Application of 1-alkyl-3-methylimidazolium-based ionic liquids in non-aqueous
      capillary electrophoresis.
AB  - In many cases salts, which are liquid at room temperature show a better
      solubility in organic solvents, and can be used in nonaqueous capillary zone
      electrophoresis as ionic additives. In this study 1-alkyl-3-methylimidasolium
      based ionic liquids were used as additives in separation media to assess the
      interactions between the analytes and the ionic additive present and to find an
      influence of the type and concentration of the ionic additive, also the nature of
      the nonaqueous medium employed. Different organic solvents (acetonitrile and
      methanol) contribute differently to the conversion of analytes into a charged
      form. Complexes with either an anionic or a cationic part of the ionic liquid
      additive were formed. This was the case for electrophoresis separation of
      Bronsted acids and polyphenolic compounds.

PMID- 12498232
TI  - Evaluation and optimization of capillary zone electrophoresis with different
      dynamic capillary coatings for the determination of carbohydrate-deficient
      transferrin in human serum.
AB  - Serum transferrin (Tf) comprises several isoforms with up to two complex
      oligosaccharide chains containing zero to eight sialic acid residues and neutral
      sugars. The major glycoform, known as tetrasialo-Tf, contains four sialic acid
      residues and accounts for about 80% of whole Tf in human serum. Carbohydrate
      deficient transferrin (CDT) encompasses isoforms that are deficient in
      carbohydrate chains and consequently in sialic acid residues (including asialo-,
      monosialo- and disialo-Tf) and is a well known marker for chronic alcohol abuse.
      Recently capillary zone electrophoresis (CZE) has been reported as a tool
      extremely effective for the simultaneous, individual, quantitative determination
      of CDT isoforms. Three CZE methods that feature different dynamic capillary
      coatings were evaluated and optimized for CDT determination in human serum of
      alcohol abusers and control subjects. CZE separation was performed in alkaline
      borate buffers after serum sample saturation with iron, electropherograms were
      detected at 200 nm, data were evaluated as % area of disialo-Tf in relation to
      tetrasialo-Tf and peak identification was accomplished via relative migration
      times to tetrasialo-Tf, immunosubtraction and enzymatic sequential cleavage of
      sialic acid residues. Dynamic capillary coatings with diaminobutane, spermine and
      a double coating produced by commercially available proprietary agents were
      investigated and found to be suitable for determination of CDT in human serum.
      For all three approaches, best results were obtained in 50 microm I.D. fused
      silica capillaries of 50 cm effective length and a capillary cartridge
      temperature of 20-25 degrees C. Using 3 mM 1,4-diaminobutane or 0.02 mM spermine
      in a borate-based running buffer of pH 8.3 provided data of remarkable similarity
      with resolution of di-, tri-, tetra- and pentasialo-Tf within 15-18 min. With the
      double coating, asialo-Tf and Tf isoforms with two to six sialic acid residues
      were baseline separated. Compared to the two amine-based procedures, the run
      times were found to be somewhat shorter, the detector signals higher, the applied
      power level significantly lower and the reproducibility better.

PMID- 12498233
TI  - Evaluation of calibration data in capillary electrophoresis using artificial
      neural networks to increase precision of analysis.
AB  - Increase of precision in capillary electrophoresis can be achieved applying
      suitable markers and evaluating calibration curves and data analysis with
      artificial neural networks. They are able to account for errors in both x- and y
      axes, nonlinear response of detector and non-linearity of calibration curves
      eventually. A comparison of the artificial neural networks approach with ordinary
      least-squares (OLS) and bivariate least-squares regression (BLS) was done. While
      OLS and BLS give similar results, the method proposed and tested in analysis of
      several pharmaceutical products yields lower prediction errors than traditional
      linear least-squares methods and the precision of analysis was found in the range
      0.5-1.5% relative.

PMID- 12498234
TI  - Sample pre-concentration by isotachophoresis in microfluidic devices.
AB  - We have designed microfluidic devices with the aim of coupling isotachophoresis
      (ITP) with zone electrophoresis (ZE) as a method to increase the concentration
      limit of detection in microfluidic devices. We used plastic multi-channel chips,
      designed with long sample injection channel segments, to increase the sample
      loading. The chip was designed to allow stacking of the sample into a narrow band
      by discontinuous ITP buffers and subsequent separation in the ZE mode. In the ITP
      ZE mode, with a 2-cm long sample injection plug, sensitivity was increased by 400
      fold over chip ZE and we found that the separation performance after the ITP
      stacking was comparable to that of regular chip ZE. We report sub-picomolar
      limits of detection of fluorescently labeled ACLARA eTag reporter molecules
      electrokinetically injected from cell lysate sample matrixes containing moderate
      salt concentrations. We evaluated sample injections from buffers with varied
      ionic strengths and found that efficient stacking and separations were obtained
      in both low and high conductivity buffers, including physiological buffer with at
      least 140 mM salt. We applied ITP-ZE to the analysis of a cell surface protease
      (ADAM 17) which used live intact cells in physiological buffers with detection
      limits below 10 cells/assay.

PMID- 12498235
TI  - Two dimensional mapping of cancer cell extracts by liquid chromatography
      capillary electrophoresis with ultraviolet absorbance detection.
AB  - A two-dimensional liquid chromatography/capillary electrophoresis technique was
      developed for rapid and comprehensive mapping of cell extracts. The cell extracts
      were first separated by reversed-phase HPLC based on hydrophobicity. Fractions of
      the effluent from the HPLC system were collected into 96-well microtiter plates
      and dried under vacuum. The fractions were reconstituted with deionized water,
      separated by capillary array electrophoresis based on charge-to-size ratio, and
      detected by UV absorption at 214 nm. Prior to analysis by multiplexed capillary
      electrophoresis, the reconstituted fractions were concentrated on-column using
      large volume sample stacking with polarity switching. In this way, high
      resolution analysis of even the minor components in the complicated mixture was
      possible.

PMID- 12498236
TI  - Analysis of active chemical species generated by electrolysis using non-aqueous
      capillary electrophoresis. Detection of the anion radical and the divalent anion
      of tetracyanoquinodimethane.
AB  - We have investigated detection of the anion radical and the divalent anion of
      tetracyanoquinodimethane (TCNQ) by acetonitrile-CE under anaerobic conditions.
      With electrolysis at a potential of 0.0 V (vs. Ag/AgCl), an acetonitrile solution
      of TCNQ turned green, characteristic of the TCNQ anion radical (TCNQ-). Only one
      peak of the anionic compound was observed in CE of the electrolysis solution and
      it should be that of TCNQ-. Then, the electrolysis potential was shifted to -0.8
      V expected to be sufficient potential for the further reduction of TCNQ-, and the
      solution turned almost colourless. In CE analysis of the latter solution, another
      anionic component possessing a larger electrophoretic mobility than that of TCNQ-
      was detected, and it was decomposed immediately under aerobic conditions. This
      product was strongly suggested to be the divalent anion of TCNQ, and the present
      method would contribute notably to detection of the unstable species.

PMID- 12498237
TI  - Electroosmotic flow variations caused by the volatility of buffer components:
      diagnosis and therapy.
AB  - In order to separate a polar amine pharmaceutical and its potential impurities, a
      micellar electrokinetic chromatography method was developed. The main compound
      and 11 other substances were completely separated using a 20 mM Tris buffer, pH
      8.0, containing 50 mM sodium dodecylsulfate (SDS) and 24% (v/v) acetonitrile.
      However, a strong, continuous reduction in the EOF occurred and quantification
      was not possible. The EOF reproducibility could not be improved by suitable
      rinsing procedures. Surface effects or interactions did not cause the EOF
      changes, but the evaporation of acetonitrile was identified as the major source
      for EOF instability. However, a high concentration of acetonitrile was decisive
      for selectivity. Thus a reliable protection against the evaporation of this
      buffer constituent had to be found. Paraffin and various silicon oils were tested
      as covering film. In order to quickly test buffer systems if the evaporation of
      electrophoresis solutions is acceptable, an alternative experimental design
      without doing CE experiments had to be found. Electrical conductivity was chosen
      as parameter, because it can be determined simply and fast. The buffers under
      investigation were placed in a 50-ml beaker with a magnetic stirring rod, placed
      on a magnetic stirrer. The buffer solution was kept in motion at 120 rev./min.
      The beaker was covered around the measuring head with laboratory film and in
      addition to this with paraffin or silicon oil. An acetonitrile content up to 10%
      (v/v) was acceptable if a coverage was used. The various cover liquids had a
      similar effect. A content of 15% (v/v) already increased the evaporation effect
      significantly. Higher acetonitrile contents are not acceptable. A buffer similar
      to the originally transferred method, 20 mM Tris (pH 8.0), 50 mM SDS containing
      10% (v/v) acetonitrile as well as 10% (v/v) isopropanol showed an acceptably low
      evaporation in the conductivity experiments. With this buffer, a stable EOF was
      also obtained. Conductivity measurements are generally applicable to quickly test
      buffers that contain organic solvents.

PMID- 12498238
TI  - Micromachined capillary cross-connector for high-precision fraction collection.
AB  - A new approach for high-precision fraction collection of double-stranded DNA
      fragments by capillary electrophoresis coupled to a micromachined plastic
      capillary cross-connector is presented. The system design integrates four fused
      silica capillaries with an acrylic cross-channel connector. The cross-channel
      structure was introduced to enhance the efficiency of the fraction collection
      process by electrokinetic manipulations. Following the detection of the sample
      zone of interest at or slightly upstream of the cross during the separation mode,
      the potentials were reconfigured to collection mode to direct the selected
      analyte zone into the corresponding collection vial, while keeping the rest of
      the sample components virtually stopped within the separation capillary. In this
      way the spacing between consecutive bands of interest can be physically
      increased, allowing precise isolation of spatially close sample zones. After
      collection of the target fraction the separation mode is resumed, and the
      separation/collection cycle is repeated until all desired sample zones are
      separated and captured. The capillary cross-connector was fabricated of a
      transparent acrylic substrate by microdrilling flat end and through channels,
      matching precisely the O.D. and I.D. of the connected capillary tubing,
      respectively. This design provided a close to zero dead volume connection
      assembly for the separation and collection capillaries causing minimal extra band
      broadening during high-precision micropreparative DNA fractionation.

PMID- 12498239
TI  - Separation of aromatic aminophosphonic acid enantiomers by capillary
      electrophoresis with the application of cyclodextrins.
AB  - The detailed studies concerning capillary electrophoresis separation of
      aminophosphonic acid enantiomers with various commercially available
      cyclodextrins are presented. The obtained results show that the separation of
      these stereoisomers is dependent on pH of background electrolyte, concentration
      of cyclodextrin as well as on the type of applied chiral selector. The separation
      mechanism is based on the co-operative effect of hydrogen bond type interactions
      enhanced by hydrophobic forces and sterical constrains between aminophosphonate
      and cyclodextrin. With application of elaborated method, enantiomeric baseline or
      partial separation of 18 alpha-aminophosphonic acids was achieved. This
      separation can be successfully used for routine aminophosphonic acids
      enantiopurity determination.

PMID- 12498240
TI  - Effect of feed zone width on product purity in preparative-scale, continuous free
      flow isoelectric focusing separation of enantiomers.
AB  - The effects of the increased width of the sample feed stream upon the purity of
      the collected fractions were examined in the continuous free-flow isoelectric
      focusing separation of the enantiomers of dansyl-tryptophan. Compared to the
      reference separation obtained with a narrow feed stream introduced through the
      central sample feed port of the continuous free-flow isoelectric focusing
      separation unit, the final pH gradient, the position of the enantiomer band
      centroids and the values of the cumulative product recoveries and cumulative
      product purities remained essentially identical as the width of the feed band of
      the racemic sample dissolved in the carrier ampholyte was increased up to the
      full width of the separation chamber suggesting that the current, limiting
      practice of narrow, central feed bands can be safely abandoned and dilute
      feedstock solutions can be utilized in preparative-scale isoelectric focusing
      enantiomer separations.

PMID- 12498241
TI  - On-line sample preconcentration in micellar electrokinetic chromatography using
      ion-pair reagents.
AB  - To improve the detection sensitivity of some aromatic carboxylic acids and
      naphthalenesulfonic acids, the use of ion-pair reagents was examined in sweeping
      micellar electrokinetic chromatography (MEKC) with an anionic sodium dodecyl
      sulfate (SDS) micelle. Tetraalkylammonium (TAA) salts were used as ion-pair
      reagents to improve the sweeping efficiency. The effects of the alkyl chain
      length of the TAA groups and the TAA salt concentration on sweeping were
      examined. Under optimized conditions, about 400-fold enhancement in detection
      sensitivity was obtained in terms of peak heights by addition of ion-pair
      reagents in sweeping MEKC. This value was about 10 times greater than that
      obtainable by the SDS micelle used alone.

PMID- 12498242
TI  - Simultaneous separation of different enantiomeric pairs in capillary
      electrophoresis by mixing different hemispherodextrins, a very versatile class of
      receptors.
AB  - Six different racemates of the profen family were used as analytes in order to
      test the chiral selector properties of three members of a new class of
      cyclodextrin derivatives, hemispherodextrins (HMs), in capillary electrophoresis.
      In addition to experiments carried out to separate each enantiomeric pair one by
      one, other experiments were carried out on samples containing all six
      enantiomeric pairs. Electropherograms were obtained either by adding a single HM
      to the background electrolyte (BGE), or a binary mixture of HMs. The results
      obtained confirm the excellent chiral selector properties of the HMs, and
      furthermore show that these compounds can also be used for achiral selection.
      When mixing different HMs, a complementary effect in chiral selectivity is
      observed, which, in our opinion, deserves further study.

PMID- 12498243
TI  - Voltage-addressable on/off microvalves for high-pressure microchip separations.
AB  - We present a microchip-based, voltage-addressable on/off valve architecture that
      is fundamentally consistent with the pressures and solvents employed for high
      pressure liquid chromatography. Laser photopatterning of polymer monoliths inside
      glass microchannels is used to fabricate mobile fluid control elements, which are
      opened and closed by electrokinetic pressures. The glass substrates and
      crosslinked polymer monoliths operate in water-acetonitrile mixtures and have
      been shown to hold off pressures as high as 350 bar (5000 p.s.i.). Open/closed
      flow ratios of 10(4) to 10(6) have been demonstrated over the pressure range 1.5
      70 bar (20-1000 p.s.i.), and the pressure-leak relationship shows the potential
      for valving control of flow through packed or monolithic chromatography columns.
      We expect that this valve platform will enable multiplexing of multiple
      chromatographic separations on single microchips.

PMID- 12498244
TI  - Preparative-scale isoelectric trapping separations using a modified Gradiflow
      unit.
AB  - The Gradiflow BF200 preparative electrophoretic unit (Gradipore), which has been
      developed for size-based and charge-sign-based protein separations and in which
      the hydraulic flow path of the recirculating sample stream in the separation
      cartridge is orthogonal to the electric field, has been modified to carry out
      binary protein separations using the principles of isoelectric trapping. The
      disposable separation cartridge contained three isoelectric membranes which,
      along with the cartridge holder, formed the anode and cathode compartments and
      the anodic and cathodic separation compartments. The utility of the modified
      instrument was demonstrated by effecting a binary separation of chicken egg white
      across an isoelectric point 5.5 isoelectric membrane. The desalting and
      subsequent binary separation steps proved to be remarkably rapid, due to the
      favorable combination of short electrophoretic path, high electric field strength
      and large effective isoelectric membrane surface area.

PMID- 12498245
TI  - Combination of liquid-phase microextraction and on-column stacking for trace
      analysis of amino alcohols by capillary electrophoresis.
AB  - We described a new method for the enrichment of basic drugs present in water
      samples via liquid-phase microextraction (LPME) combined with on-column stacking
      in capillary electrophoresis. Two steps were employed to enhance the detection
      sensitivity of four amino alcohols. The analytes were first extracted from
      aqueous sample (donor solution) that were adjusted to basic through a thin layer
      of 1-octanol entrapped within the pores of a polypropylene hollow fiber, and then
      into a 5-microl acidic acceptor solution inside the hollow fiber. The extract was
      then further enriched through on-column stacking in capillary electrophoresis.
      With this two-step enrichment procedure, the method provided 72-110-fold
      preconcentration of the target amino alcohols. The limits of detection were 0.08
      0.5 microg/ml. Relative standard deviation (n=6) ranged between 4.3 and 6.9% for
      the studied drugs utilizing 2-amino-1-phenylethanol as internal standard. The
      extraction of amino alcohols in spiked urine samples was evaluated using the
      developed procedure.

PMID- 12498246
TI  - Electrophoretic analysis of amines using reversed-phase, reversed-polarity, head
      column field-amplified sample stacking and laser-induced fluorescence detection.
AB  - This paper describes the use of reversed-phase, reversed-polarity head-column
      field-amplified sample stacking (HCFASS) for on-line sample concentration in
      conventional capillary electrophoresis. The effective stacking efficiency was
      determined as a function of sodium hydroxide concentration in the sample matrix.
      Results concur with theoretical predictions where stacking efficiency depends on
      the conductivity (electric field strength) and electrophoretic mobility in the
      sample matrix solution. Fluorescein isothiocyanate-derivatized aniline and 2,4
      dimethylaniline were dissolved in sodium hydroxide (800 microM), separated in a
      phosphate running buffer (0.05 M, pH 9.0) and detected utilising laser-induced
      fluorescence. The use of reversed-phase, reversed-polarity HCFASS with laser
      induced fluorescence detection yielded sensitivity improvements with respect to
      normal injection schemes in excess of three orders of magnitude, and a limit of
      detection as low as 10(-13) M.

PMID- 12498247
TI  - Analysis of catecholamines by capillary electrophoresis and capillary
      electrophoresis-nanospray mass spectrometry. Use of aqueous and non-aqueous
      solutions compared with physical parameters.
AB  - Catecholamines were analysed in aqueous and alcoholic non-aqueous solutions by
      capillary electrophoresis and capillary electrophoresis-mass spectrometry using
      sheathless nanospray coupling. Decreases in the electrophoretic mobilities of the
      catecholamines and in the electroosmotic mobilities were observed from water to 1
      propanol. Separations were more efficient in all non-aqueous media than in water.
      The diffusion coefficients of the catecholamines in the different media were
      determined. The solvent had little effect on the sensitivity of the UV or MS
      detection. Both methods were successfully applied to the analysis of urine
      samples.

PMID- 12498248
TI  - Separation and enantioseparation of derivatized amino acids and biogenic amines
      by high-performance liquid chromatography with reversed and chiral stationary
      phases.
AB  - This study demonstrates that an amino-beta-cyclodextrin-bonded phase column
      exhibits enantioselectivity for various amino acid derivatives. Mixtures of
      methanol, acetonitrile, tetrahydrofuran or dioxan and triethylamine buffers (pH
      4.0-7.0) were used as mobile phases. The effect of the mobile phase on the
      resolution process was studied by varying the mobile phase composition (type and
      percentage of organic modifiers, pH, and ionic strength of the buffer solution).
      The 1-octanol-water partition coefficients are calculated and tabulated for 16
      derivatized amino acids. The chromatographic data for 42 pairs of derivatized
      amino acids resolved on the amino-beta-cyclodextrin-bonded phase are summarised.
      The separation of adrenaline, noradrenaline and amphetamine on a novel vancomycin
      stationary phase is demonstrated.

PMID- 12498249
TI  - Direct monitoring of glycohemoglobin A1c in the blood samples of diabetic
      patients by capillary electrophoresis. Comparison with an immunoassay method.
AB  - The capillary electrophoresis (CE) study was focused on quantifying
      glycohemoglobin A1c, HbA1c, in whole blood samples of patients suffering diabetes
      mellitus. The results showed that dynamic polyionic coating of the capillary made
      the method very reproducible. The precision evaluation, method comparison and
      bias estimation in CE were performed during 20 days with patient blood samples
      and with four control samples. The influence of the storage time and temperature
      on the glycohemoglobin levels were also tested. High resolution in CE could be
      used to show evidences of the ageing of the samples stored at -70 degrees C. The
      results showed that the ageing peak was not originated from HbA1c, because it did
      not affect the HbA1c level which was in balance with the results of fresh samples
      measured with immunoassay. The HbA1c % values of blood samples of 105 patients
      measured with the CE technique varied between 3.6 and 11.8 and they were
      approximately 2-3% lower than measured with immunoassay. The correlation (R2) of
      CE results with immunoassay and HPLC results were 0.962 and 0.781, respectively.

PMID- 12498250
TI  - Choice of different dyes to label tyrosine and nitrotyrosine.
AB  - In this work, we will present some attempts to analyze tyrosine and nitrotyrosine
      using capillary electrophoresis and either UV-Visible detection or laser-induced
      fluorescence (LIF) detection. An argon ion (488 nm) laser is used for fluorescein
      isothiocyanate (FITC) and 7-fluoro-4-nitro-2,1,3-benzoxadiazole (NBD-F). A near
      infrared (780 nm) laser is used for NIR 780 derivatives. The UV-Visible limit of
      detection is 2.5 microM whereas it is in the range of 30 nM for LIF detection.

PMID- 12498251
TI  - Determination of recombinant hirudin structural deviants by capillary zone
      electrophoresis augmented with buffer additives.
AB  - The polypeptide hirudin is a potent and specific thrombin inhibitor used in
      anticoagulant therapy and naturally occurring in medicinal leech. Using gene
      technology methods, recombinant (r) hirudin can be produced on a large scale.
      Purity evaluation of the synthesized r-hirudin is essential to monitor co
      expressed structural deviants and degradation products before therapeutic use.
      Although the well established RP-HPLC analysis appears to be the method of
      choice, in the case of r-hirudin baseline separation of the structural deviants
      is not necessarily achieved. Capillary zone electrophoresis augmented with buffer
      additives was used as a complementary technique to separate r-hirudin
      successfully from several similar species, in order to provide characterization
      information, as well as performing purity control and stability studies.

PMID- 12498252
TI  - Rapid method for the determination of amino acids in serum by capillary
      electrophoresis.
AB  - A rapid method for the determination of amino acids in serum is presented. The
      derivatization of amino acids with 2,4-dinitrofluorobenzene was performed in 0.5
      M sodium borate (pH 9.5). The complete separation of derivatives of 16 amino
      acids and an internal standard (D-norleucine) was achieved within 8 min by
      capillary zone electrophoresis. The running buffer consisted of 30 mM sodium
      tetraborate (pH 9.8)-isopropanol-30% Brij 35 (825:150:25, v/v). The capillary
      used had an internal diameter of 75 microm and an effective length of 300 mm. A
      voltage of 28 kV was applied. Temperature was maintained at 15 degrees C.
      Detection was 360 nm. The assay was linear from 10 to 700 microM. The minimal
      detection limit was 2.5-7.9 microM. The recovery of amino acids added to serum
      samples was 86.3-107.4%. Within-run precision was 2.8-10.3%, and between-run
      precision was 3.5-11.6%. The concentrations of amino acids in serum of 32
      patients with chronic renal failure were measured. Among them, the levels of
      serine, isoleucine and valine were significantly lower than those of healthy
      volunteers (P<0.01), but the concentrations of cystine, tryptophan and phenylane
      were significantly higher than those of healthy volunteers (P<0.01). The result
      showed that the method could be used for determining amino acids in clinical
      practice and scientific research.

PMID- 12498253
TI  - Microcolumns with self-assembled particle frits for proteomics.
AB  - LC-MS-MS experiments in proteomics are usually performed with packed microcolumns
      employing frits or outlets smaller than the particle diameter to retain the
      packing material. We have developed packed microcolumns using self-assembled
      particles (SAPs) as frits that are smaller than the size of the outlet. A five to
      one ratio of outlet size to particle diameter appears to be the upper maximum. In
      these situations the particles assembled into an arch over the outlet like the
      stones in a stone bridge. When 3 microm particles were packed into a tapered
      column with an 8 microm outlet, two particles bridged the outlet with 0.3 pl dead
      volume and perfect success rate. In peptide analysis by LC-MS, the peak width at
      half height was normally less than 6 s, compared to 12 s without SAPs. The LC-MS
      MS system provided 37% sequence coverage (21 matched peptides) for a tryptically
      digested sample of 10 fmol bovine serum albumin. We also describe application of
      the SAP principle to make disposable pipette tip columns with short pieces of
      fused-silica capillary as the outlet.

PMID- 12498254
TI  - Miniaturized membrane-based reversed-phase chromatography and enzyme reactor for
      protein digestion, peptide separation, and protein identification using
      electrospray ionization mass spectrometry.
AB  - A commonly used capillary fitting is employed for housing miniaturized membrane
      chromatography for performing reversed-phase peptide separations. By placing a
      hydrophobic and porous polyvinylidene fluoride membrane around the end of a
      polymer sleeve, the assembly of capillary fitting not only provides the
      stationary phase, but also establishes the necessary flow paths using capillary
      connections. The miniaturized membrane chromatography system is coupled with a
      micro-enzyme reactor containing immobilized trypsins for performing rapid protein
      digestion, peptide separation, and protein identification using electrospray
      ionization mass spectrometry. Separation performance of cytochrome c digest in
      miniaturized membrane chromatography is compared with the results obtained from
      micro-LC and capillary LC. The efficacy and the potentials of miniaturized
      membrane chromatography in tryptic mapping are reported. The use of miniaturized
      membrane chromatography allows significant reduction in sample consumption
      together with enhanced detection sensitivity. By minimizing the void volume in
      miniaturized membrane chromatography, the elution times of cytochrome c peptides
      are significantly shortened in this study in comparison with our previous
      results, and are comparable with those in micro-LC and capillary LC using
      considerably higher mobile phase flow-rates.

PMID- 12498255
TI  - Evidence for oligomerization of metallothioneins in their functional state.
AB  - Capillary zone electrophoresis in the polyacrylamide-coated capillary was used to
      study metallothionein (MT) isoforms at physiological pH in horse kidney and
      rabbit liver MT preparations produced commercially by Sigma. Evidence is put
      forward that MT develops oligomers or aggregates in its metal binding situation
      at these pH values in both species. For the horse kidney preparation two forms
      were found for both the MT-IA and the MT-IB forms, for the rabbit liver three
      forms could be seen for the MT-I form and two for the MT-II form. At pH values
      above the physiological range (pH 8-10) up to four forms could be seen for the MT
      I form (MT-IA in the horse) in both preparations. Compared to the MTCd-II form,
      the rabbit liver MTZn-II form not only behaved electrophoretically identical, but
      also showed a corresponding oligomerization behaviour. Our results indicate that
      the oligomerized MT-I form in the rabbit liver and the MT-IA form in the horse
      kidney bind more Cd atoms than the expected number of 7 per monomer.

PMID- 12498256
TI  - Assay of total homocysteine and other thiols by capillary electrophoresis and
      laser-induced fluorescence detection. II. Pre-analytical and analytical
      conditions.
AB  - In recent papers, we presented a new analytical method for thiol quantification
      in serum. This method was developed with capillary electrophoresis (CE) and laser
      induced fluorescence (LIF) to analyze thiol-iodoacetamidofluoresceine (IAF)
      derivatives. Quantitative results for homocysteine, glutathione,
      cysteinylglycine, and cysteine were presented (Causse E., et al., Clin. Chem. 45
      (1999) 412). An exhaustive comparison of the quantitation of homocysteine in
      plasma, using high-performance liquid chromatography with either conventional
      fluorescence detection or fluorescence polarization immunoassay was also reported
      (Causse E., et al., Electrophoresis 21 (2000) 2074). Sample preparation prior to
      derivatization with IAF had never been investigated. Recently we studied protein
      precipitation in serum with different organic agents (Causse E., et al., J.
      Chromatogr. A 895 (2000) 173). In this work, we evaluated the conditions of
      protein precipitation in function of the amounts of acetonitrile and their
      influence on quantitation and quality of the electropherograms. Then, we looked
      at the variation of thiol concentrations in the haemolysis states and studied the
      thiol stability of blood samples cooled on ice.

PMID- 12498257
TI  - On-line concentration of trace proteins by pH junctions in capillary
      electrophoresis with UV absorption detection.
AB  - We report an on-line concentration approach based on pH junctions for the
      analysis of trace proteins under acidic conditions by capillary electrophoresis
      (CE) with UV absorption detection. Stacking is due to decreases in the
      electrophoretic mobilities of proteins when migrating from the sample zone to a
      relatively high-pH buffer filled in the capillary. Acidic buffers prepared from
      tris(hydroxymethyl)aminomethane (co-ions) and propanoic acid were suitable. With
      respect to speed, resolution, and stacking efficiency, it is appropriate to
      conduct the analysis of proteins under discontinuous conditions: pH 3.8 (inside
      the capillary), 2.8 (protein samples), and 3.3 (anodic reservoir). To minimize
      protein adsorption on the capillary wall, capillaries dynamically coated with
      single, double, and triple layers of polymers have been made and tested.
      Capillaries dynamically coated with three layers of neutral, cationic and neutral
      polymers in sequence were used to separate four proteins with good
      reproducibility. When using a 60-cm capillary, the peak height increased linearly
      with the injection volume up to 1.42-microl and peak profiles were sharp,
      indicating stacking of proteins. As a result, the limits of detection for
      lysozyme, myoglobin, carbonic anhydrase, and alpha-lactalbumin were 1.9, 3.2,
      11.3 and 6.5 nM, respectively. Furthermore, this method has been applied to the
      analysis of about 1.31 and 0.66 microl of 5.00 and 0.20 microM peptic and tryptic
      digests of beta-casein, with results of detecting 26 and 12 peaks in 21 and 14
      min, respectively.

PMID- 12498258
TI  - Extension of separation range in capillary isoelectric focusing for resolving
      highly basic biomolecules.
AB  - The non-availability of commercial carrier ampholytes in the pH range greater
      than 11 has contributed to difficulties in focusing and resolving highly basic
      proteins/peptides using capillary isoelectric focusing (cIEF). Two different
      approaches, involving the use of N,N,N',N'-tetramethylethylenediamine (TEMED) and
      ampholyte 9-11, are investigated for their effects on the extension of separation
      range in cIEF. The addition of TEMED into pharmalyte 3-10 not only prevents the
      peptides/proteins from focusing in sections of the capillary beyond the detection
      point, but also extends the separation range to at least isoelectric point (pI)
      12. The combination of ampholyte 9-11 with pharmalyte 3-10 surprisingly provides
      baseline resolution between bradykinin (pI 12) and cytochrome c (pI 10.3). The
      sample mixture, containing bradykinin, the high-pI protein calibration kit (pI
      5.2-10.3), and cytochrome c digest, is employed to demonstrate the cIEF
      separation of proteins and peptides over a wide pH range of 3.7-12.

PMID- 12498259
TI  - Capillary electrophoresis study of outer membrane proteins of Pseudomonas strains
      upon antibiotic treatment.
AB  - Nosocomial wound infections by Pseudomonas aeruginosa strains have increasing
      importance in orthopaedic surgery. Outer membrane protein composition and cell
      surface hydrophobicity of the bacteria have strong influence on adhesion to
      living tissues or artificial medical devices. Outer membrane proteins of five
      Pseudomonas strains (KT 2, KT 7, KT 25, KT 28, KT 39) isolated from orthopaedic
      patients' wounds and one standard strain NIH Hungary 170000 isolated from pus
      were examined. The capillary electrophoretic patterns of the outer membrane
      proteins were characteristic to each bacterial strains possessing different
      relative ratios of major and minor proteins. Antibiotic treatment of bacteria
      with three antibiotics, cefotaximum, amoxicillinum/clavulinic acid and amikacinum
      (applied often in prophylaxis and treatment of patients) induced changes in the
      electrophoretic profiles showing that outer membrane protein composition was
      altered significantly. The most pronounced alterations in the electrophoretic
      patterns after antibiotic treatment were obtained in the cases of the strains KT
      2, KT 7 and KT 28. The amikacinum administration strongly decreased the relative
      percentage of the 38800 rel. mol. mass protein in KT 2 (from 20 to 6%). while the
      relative amount of the same protein increased significantly in KT 7 and KT 28
      after cefotaximum treatment (from 2 to 16% and from 12 to 28%, respectively).
      Decrease in cell-surface hydrophobicity was also observed by salt aggregation
      test. The results obtained can be used to determine the therapeutic
      concentrations of antibiotics to induce changes in the adhesion properties of
      bacteria.

PMID- 12498260
TI  - Potential binding of borate ions to mono- and oligonucleotides: a capillary
      electrophoresis investigation.
AB  - The potential binding of borate to oligonucleotides and DNA fragments is here
      investigated. In case of free nucleotides, such as AMP, there appears to be a
      weak binding, although no free versus complexed species could ever be separated
      under any experimental condition. The binding was suggested by the strong peak
      asymmetry and by the fact that, at progressively lower borate molarities in the
      background electrolyte, the peak shape suddenly switched from fronting to
      tailing. This indicated, as also confirmed by theoretical simulations, that the
      AMP-borate complex was the slow, not the fast moving species. On the contrary, in
      the case of free adenosine, strong binding ensued, since in Tris-acetate buffer
      this compound was only eluted with the electroendoosmotic flux, being neutral,
      whereas in Tris-borate it had a much higher mobility, comparable to, although
      lower than, that of AMP. When running oligonucleotides, at standard borate
      molarities (ca. 45 mM), and under strict iso-ionic strength conditions, no
      binding to borate could be demonstrated, since the free mobility of a 24-mer DNA
      was identical in TA and TB buffers. However, at very high borate molarities (200
      mM) and high pH values (pH 8.92), some binding to oligonucleotides could occur,
      since in these latter conditions the mobility of a 24-mer was seen to be ca. 20%
      lower than at pH 7.69, a pH value that should discourage any complex formation.

PMID- 12498261
TI  - Comparison of the separation of large DNA fragments in the presence and absence
      of electroosmotic flow at high pH.
AB  - This paper describes the analysis of large DNA fragments at pH > 10.0 by
      capillary electrophoresis (CE) in the presence of electroosmotic flow (EOF) using
      hydroxyethylcellulose (HEC) solution. HEC solution in the anodic reservoir enters
      the capillaries filled with high-pH buffer by EOF after sample injection. With
      respect to resolution, sensitivity, and speed, separation conducted under
      discontinuous conditions (different pH values of HEC solutions and buffer filling
      the capillary) is appropriate. Using HEC solution at concentrations higher than
      its entanglement threshold ensures a good separation of large DNA fragments in
      the presence of EOF at high pH. In addition to pH and HEC, the electrolyte
      species, dimethylamine, methylamine, and piperidine, play different roles in
      determining the resolution. The separation of DNA fragments ranging in size from
      5 to 40 kilo base pairs was completed in 6 min using 1.5% HEC prepared in 20 mM
      methylamine-borate, pH 12.0, and the capillary filled with 40 mM dimethylamine
      borate, pH 10.0. In comparison, this method allows faster separations of large
      DNA fragments compared with that conducted in the absence of EOF using dilute HEC
      solutions.

PMID- 12498262
TI  - Handling and detection of 0.8 amol of a near-infrared cyanine dye by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - We are interested in the detection of DNA adducts and other trace analytes by
      labeling them with a fluorescent tag followed by use of capillary electrophoresis
      with laser-induced fluorescence detection (CE-LIF) for high resolution and
      sensitivity. Towards this goal, here we report the following: (1) synthesis and
      handling properties of a near-IR, carboxyl-substituted heptamethine cyanine dye;
      (2) modification of an existing ball lens LIF detector to provide near-LIF
      detection with excitation at 785 nm for CE; and (3) corresponding handling and
      detection of as little as 0.8 amol of the dye by enrich-injection of 4.7 microl
      of 1 x 10(-13) mol/l dye in methanol from an 8-microl volume into a corresponding
      CE-LIF system. The electrolyte for the separation was methanol-40 mmol/l aqueous
      sodium borate (98:2, v/v). This finding encourages further exploration of the dye
      by functionalization of its carboxyl group for chemical labeling purposes.

PMID- 12498263
TI  - Application of micellar electrokinetic chromatography to the determination of
      sultamicillin in oral pharmaceutical preparations.
AB  - A micellar electrokinetic capillary electrophoretic method for determination of
      sultamicillin in Unasyn oral preparations--tablets and suspension--was evaluated.
      Phosphate-borate buffer at pH 7.0 containing 1.0% sodium dodecylsulfate was used
      as a mobile phase. The elaborated method ensures separation of sultamicillin from
      p-toluenesulfonic acid and the impurities, ampicillin, sulbactam and
      penicillamine. The method was validated for specificity, reproducibility,
      precision, accuracy and assay linearity (in a concentration range of
      sultamicillin of 0.05-1.5 mg/ml). Statistical analysis by Student's t-test showed
      no significant differences between the results obtained by micellar
      electrokinetic chromatography and HPLC, t(calculated) 0.519 for suspension assays
      and 0.284 for tablets assays were smaller then t(tabulated).

PMID- 12498264
TI  - Optimization and validation of a capillary zone electrophoretic method for the
      analysis of several angiotensin-II-receptor antagonists.
AB  - We optimized a capillary zone electrophoretic method for separation of six
      angiotensin-II-receptor antagonists (ARA-IIs): candesartan, eprosartan,
      irbesartan, losartan potassium, telmisartan, and valsartan. A three-level, full
      factorial design was applied to study the effect of the pH and molarity of the
      running buffer on separation. Combination of the studied parameters permitted the
      separation of the six ARA-IIs, which was best carried out using 60 mM sodium
      phosphate buffer (pH 2.5). The same system can also be applied for the
      quantitative determination of these compounds, but only for the more soluble
      ones. Some parameters (linearity, precision and accuracy) were validated.

PMID- 12498265
TI  - Peak compression effects in capillary electrochromatography of basic drug
      substances using a strong cation-exchanger.
AB  - Peak compression effects in capillary electrochromatography of basic drug
      substances using a strong cation-exchanger have been studied. Extremely narrow
      peaks with apparent efficiencies of several million plates per meter could be
      obtained when the composition of the sample zone differed from that of the mobile
      phase. The increased efficiencies were predominately observed when the analyte
      had an elution time similar to that of the electroosmotic flow marker. Peak
      compression was found to be reproducible and could be obtained for all
      investigated basic drug substances by altering the composition of the mobile
      phase in such a way that the analyte co-eluted with the sample zone. An
      explanation of the observed phenomena is proposed. A sample zone differing in
      composition from the mobile phase will disturb the equilibrium between the
      stationary and mobile phase. The elution rate of an analyte will consequently be
      different when residing inside the sample zone. If the analyte migrates through
      the sample zone at a higher speed than the rest of the mobile phase and is
      strongly retained after passing through a boundary in the sample zone, a
      continuous stacking can be obtained trapping the analyte as a very narrow band.

PMID- 12498266
TI  - Analysis of illicit amphetamine seizures by capillary zone electrophoresis.
AB  - Capillary zone electrophoresis was applied for the determination of amphetamine
      and related substances in seized drugs. A buffer made of 0.1 M phosphoric acid
      adjusted to pH 3.0 with triethanolamine was selected. With this background
      electrolyte, triethanolamine is adsorbed to the capillary wall and the
      electroosmotic flow is reversed. This gives rise to peaks with good symmetry,
      high efficiency and reproducible migration times. The separation of the different
      analytes was performed in a fused-silica capillary thermostatted at 25 degrees C
      and the applied voltage was 25 kV. Under these experimental conditions,
      amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4
      methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethamphetamine, N-methyl
      1-(1,3-benzodioxol-5-yl)-2-butamine and ephedrine were resolved within 8 min and
      without interference from adulterants usually found in illicit powders. Their
      identification by the migration time was confirmed by their UV spectra recorded
      with a diode array UV detector (190-350 nm). The selected method was then applied
      to identify these substances in illicit tablets known as "Ecstasy" and the MDMA
      determined in these samples according to a laboratory validation procedure.

PMID- 12498267
TI  - Therapeutic drug monitoring of lamotrigine using capillary electrophoresis.
      Evaluation of assay performance and quality assurance over a 4-year period in the
      routine arena.
AB  - The performance of a capillary zone electrophoresis (CZE)-based assay for
      lamotrigine (LAMO) in human plasma and serum with complete internal and external
      quality assurance over an extended period of time is reported. The assay,
      originally reported by Shihabi and Oles [J. Chromatogr. B 683 (1996) 119], is
      based upon protein precipitation by acetonitrile and analysis of an aliquot of
      the acidified supernatant and was adopted in our laboratory for routine use with
      multi-level internal calibration on different commercial instruments. Evaluation
      of the calibration and control data of 103 sets of analysis and data from four
      years of external quality assurance based upon analysis of four-monthly sera
      containing LAMO and eight other anticonvulsants in sub-therapeutic, therapeutic
      or toxicological concentration levels revealed the robustness of the CZE-based
      assay and its suitability for therapeutic drug monitoring of LAMO in a routine
      setting. CZE data obtained in single determinations were found to compare well
      with the spike values and the mean of HPLC data determined in 50-70 laboratories.
      Furthermore, the gathered data were evaluated retrospectively using single-level
      internal calibration. When applied with caution, this approach was determined to
      produce slightly higher but otherwise equivalent drug concentrations. For the 4
      years of routine operation with external quality control, the reported laboratory
      ranking was between 19 (out of 67 participating laboratories) and 43 (69). This
      is the first account of a CZE-based drug assay with complete external quality
      assessment.

PMID- 12498268
TI  - Rapid screening of pKa values of pharmaceuticals by pressure-assisted capillary
      electrophoresis combined with short-end injection.
AB  - A method applying pressure-assisted capillary electrophoresis combined with short
      end injection has been developed for the rapid screening of the pKa values of
      pharmaceuticals. The electrophoretic separation is performed on a short capillary
      length with short-end injection under an applied pressure, and the effective
      mobility is measured in a series of 10 different buffers with constant ionic
      strength (I = 0.05). The application of pressure not only reduces migration
      times, particularly in lower pH buffers, but also improves the repeatability of
      effective mobility measurements. The influence of pressure on the effective
      mobility was investigated at various pH values. It was observed for the first
      time that an increase in pressure resulted in a slight decrease in the effective
      mobility when the pH was above the pKa for acidic analytes, whereas an increased
      effective mobility with increasing pressures was observed when the pH was below
      the pKa. However, the observed effective mobility shift by the applied pressure
      did not significantly affect the determined pKa values. The determined pKa values
      were in good agreement with published data. Furthermore, a stacking condition was
      applied to increase the sensitivity, and a concentration down to 2 microM could
      readily be detected with UV detection using a 50 microm I.D. capillary. This
      technique is particularly suitable for measurement of pKa values for compounds
      with poor aqueous solubility. The method also omits the commonly used
      preconditioning steps with sodium hydroxide and water. The exclusion of excessive
      preconditioning steps and the use of pressure reduces the total cycling analysis
      time, and makes it possible to determine the pKa in less than 40 min per compound
      without loss of accuracy.

PMID- 12498269
TI  - Determination of free and liposome-associated daunorubicin and daunorubicinol in
      plasma by capillary electrophoresis.
AB  - Liposomal daunorubicin (DaunoXome) is a formulation of the anticancer drug
      daunorubicin encapsulated into vesicles of about 45 nm diameter. To understand
      the pharmacodynamic relationships associated with the toxicity and efficacy of
      liposome-encapsulated daunorubicin in vivo and in vitro, it is essential to have
      a rapid method of separating the free and liposomal forms of the drug. We have
      developed and validated a method to quantify drug concentrations of liposomal
      daunorubicin, free daunorubicin and its main metabolite daunorubicinol that
      requires only 50 microl of plasma to conduct studies in children. The method
      involves the use of solid-phase extraction followed by capillary electrophoresis
      with laser-induced fluorescence (LIF) detection. With LIF detection a limit of
      quantification of 1 microg/l is obtained for the free form and the metabolite.
      Precision and accuracy are in accordance with the generally accepted criteria for
      bioanalytical methods. The method is rapid and allows for multiple samples to be
      processed simultaneously.

PMID- 12498270
TI  - Potential of formamide and N-methylformamide in nonaqueous capillary
      electrophoresis coupled to electrospray ionization mass spectrometry. Application
      to the analysis of beta-blockers.
AB  - A nonaqueous capillary electrophoresis (NACE) method, coupled with either UV or
      electrospray mass spectrometry (ESI-MS), is described for the simultaneous
      analysis of seven beta-blockers. The same electrolyte, namely 25 mM ammonium
      formate and 1 M formic acid, was used with different investigated organic
      solvents. In addition to frequently used organic solvents such as methanol (MeOH)
      and acetonitrile (MeCN), formamide and its derivatives were investigated.
      Formamide (FA) and N-methylformamide (NMF) present several interesting physico
      chemical properties, one of them being a high dielectric constant (e). Since FA
      and NMF possess a high UV cutoff, beta-blockers with an absorbance above 250 nm
      were selected as model compounds in order to compare NACE-UV and NACE-MS
      performances. FA and NMF showed different selectivity compared to water, MeOH or
      MeCN, and also demonstrated a higher efficiency in terms of the number of
      theoretical plates (especially NMF). To overcome their unfavorable optical
      properties, hyphenation with MS detection appears as a promising technique,
      thanks to its benefits in terms of selectivity, sensitivity and universality. The
      practical compatibility of FA and NMF with ESI-MS detection in combination with a
      sheath liquid configuration was demonstrated. In comparison to UV detection,
      sensitivity was increased, while a high efficiency was maintained. In addition,
      the low and stable generated currents observed were evidences for the successful
      hyphenation with ESI-MS. Hence, FA and NMF seemed to be promising alternatives in
      NACE-ESI-MS, either used as pure organic solvent or as a mixture with MeOH or
      MeCN.

PMID- 12498271
TI  - Separation and migration behavior of structurally related phenothiazines in
      cyclodextrin-modified capillary zone electrophoresis.
AB  - The influences of buffer pH and the concentration of beta-cyclodextrins (beta
      CDs) on the separation and migration behavior of 13 structurally related
      phenothiazines in CD-modified capillary zone electrophoresis (CD-CZE) using a
      phosphate background electrolyte at low pH were investigated. We focused on the
      separation of these phenothiazines, including the enantiomers of chiral analytes,
      with the use of beta-CD and hydroxypropyl-beta-CD (HP-beta-CD) as electrolyte
      modifiers or chiral selectors at concentrations less than 8 mM. The results
      indicate that the interactions of phenothiazines with beta-CDs are very strong
      and that effective separations of 13 analytes can be achieved with addition of
      0.3 mM beta-CD or 0.5 mM HP-beta-CD in a phosphate buffer at pH 3.0. Binding
      constants of phenothiazines to beta-CDs were evaluated for a better understanding
      of the interactions of phenothiazines with beta-CDs.

PMID- 12498272
TI  - Laser-induced fluorescence and UV detection of derivatized aldehydes in air
      samples using capillary electrophoresis.
AB  - In this work, two capillary zone electrophoresis methodologies using UV
      absorption detection (214 nm) and laser-induced fluorescence detection (He/Cd
      laser, 325 nm excitation, 520 nm emission) of selected aldehydes (formaldehyde,
      acetaldehyde, propionaldehyde and acrolein) derivatized with dansylhydrazine
      (DNSH, 5-dimethylaminonaphthalene-1-sulfohydrazide) were proposed and validated.
      The aldehydes react with DNSH to form negatively charged molecules in methanolic
      medium. In both methodologies, nine DNSH-derivatives, including isomers of
      acetaldehyde, propionaldehyde and acrolein and two impurities were baseline
      separated in 20 mmol l(-1) phosphate buffer at pH 7.02, in less than 9 min. The
      limits of detection for the UV and LIF methodologies ranged from 1.1-9.5 microg
      l(-1) and 0.29-5.3 microg l(-1), respectively. The applicability of both
      methodologies to contemplate real samples was confirmed in the analysis of
      aldehyde-DNSH derivatives in indoor and outdoor air samples.

PMID- 12498273
TI  - Separation and identification of aromatic acids in soil and the Everglades
      sediment samples using solid-phase microextraction followed by capillary zone
      electrophoresis.
AB  - The separation and identification of aromatic acids in soil and the Everglades
      sediment samples was carried out using solid-phase microextraction (SPME)
      followed by capillary zone electrophoresis (CZE). The soil and sediment samples
      were subject to a series of sample treatments including oxidative hydrolysis with
      molecular oxygen in a sodium hydroxide solution, acidification and filtration.
      The aromatic acids in the sample filtrate were extracted using SPME with a
      polyacrylate-coated fiber. The acids adsorbed on the fiber were subsequently
      desorbed in methanol. The desorbed acids were then separated by CZE. Several
      aromatic acids (e.g.. salicylic acid, p-coumaric acid, ferulic acid and vanillic
      acid) in both soil and sediment samples were separated, identified and
      quantified. The results of this study show that the combination of SPME with CZE
      is promising for environmental analysis.

PMID- 12498274
TI  - Separation and on-line concentration of bisphenol A and alkylphenols by micellar
      electrokinetic chromatography with cationic surfactant.
AB  - The separation and on-line concentration of bisphenol A and three alkylphenols
      were investigated by micellar electrokinetic chromatography with cationic
      surfactant. Tetradecyltrimethylammonium bromide was used as surfactant and the
      separation conditions were optimized by the addition of the organic solvents and
      cyclodextrins to the running solution. The separation of hydrophobic analytes and
      4-nonylphenol isomers was improved by the addition of 20% acetonitrile and 20 mM
      beta-cyclodextrin to the running solution. When the sweeping with the running
      solution used as the on-line concentration procedure, 56-, 67- and 29-fold
      increase in detection sensitivity of bisphenol A, 4-tert.-butylphenol and 4
      (1,1,3,3-tetramethylbutyl)phenol, respectively. The detection limits were 0.030,
      0.098 and 0.159 mg/l, respectively.

PMID- 12498275
TI  - Analysis of chitin oligosaccharides by capillary electrophoresis with laser
      induced fluorescence.
AB  - A method, using capillary electrophoresis (CE) with laser-induced fluorescence
      (LIF) detection for analyzing chitin oligosaccharides is described. Chitin
      oligosaccharides were derivatized with 9-aminopyrene-1,4,6-trisulfonate (APTS)
      via reductive amination at 37 degrees C for 16 h (optimized conditions). The APTS
      chitin oligosaccharides were analyzed using either an acidic citric acid
      phosphate buffer or an alkaline borate buffer. The effects of buffer types,
      buffer pH values, and buffer concentrations on the separation were examined. The
      analytes were successfully separated by using a pH 4.6 citric acid-phosphate
      within 19 min. The APTS-derivatized chitin monosaccharide (D-glucosamine)
      migrated first. The analytes were also completely separated by using a pH 9.0
      borate buffer within 24 min. Moreover, the specificity of enzyme digestion on
      chitin polysaccharides using the optimized APTS labeling procedure and the CE-LIF
      method was demonstrated.

PMID- 12498276
TI  - Separation and determination of nitrobenzenes by micellar electrokinetic
      chromatography and high-performance liquid chromatography.
AB  - A micellar electrokinetic chromatographic method and a high-performance liquid
      chromatographic method are proposed for the separation and determination of a
      mixture of 12 nitrobenzenes and their reduction products, namely 4-nitro-1,2
      phenylenediamine, 4-nitro-1,3-phenylenediamine, 2-nitro-1,4-phenylenediamine, 2
      nitroaniline, 3-nitroaniline, 4-nitroaniline, 4-amino-2-nitrophenol, 2-amino-5
      nitrophenol, 2-amino-4-nitrophenol, 2-nitrophenol, 3-nitrophenol, and 4
      nitrophenol. A solution of 50 mM sodium dodecyl sulfate and 10% ethanol in 23 mM
      sodium borate buffer was used as the electrophoretic medium. Good resolution
      could be obtained by the addition of tetrahydrofuran to the liquid
      chromatographic mobile phase. The retention and migration behavior of the
      nitrobenzenes are discussed.

PMID- 12498277
TI  - Novel general expressions that describe the behavior of the height equivalent of
      a theoretical plate in chromatographic systems involving electrically-driven and
      pressure-driven flows.
AB  - Novel general expressions are constructed and presented that describe the
      behavior of the height equivalent of a theoretical plate (plate height), H, as a
      function of the linear velocity, Vx, along the axis, x, of the column and the
      kinetic parameters that characterize the mass transfer and adsorption mechanisms
      in chromatographic columns. Open tube capillaries as well as columns packed with
      either non-porous or porous particles are studied. The porous particles could
      have unimodal or bimodal pore-size distributions and intraparticle convective
      fluid flow and pore diffusion are considered. The expressions for the plate
      height, H, presented in this work could be applicable to high-performance liquid
      chromatography (HPLC) and capillary electrochromatography (CEC) systems, and
      could be used together with experimental plate height, H, versus linear velocity,
      Vx, data to determine the values of the parameters that characterize
      intraparticle convective fluid flow and pore diffusion. Furthermore,
      chromatographic systems under unretained as well as under retained conditions are
      examined. The experimental values of the plate height, H, versus the linear
      velocity, Vx, for a CEC system involving charged porous silica C8 particles and
      an uncharged analyte are compared with the theoretical results for the plate
      height, H, obtained from the expressions presented in this work. The agreement
      between theory and experiment is good, and the results indicate that the
      magnitude of the intraparticle electroosmotic flow (EOF) in the pores of the
      particles is substantial while the pore diffusion coefficient was of small
      magnitude. But the overall intraparticle mass transfer resistance in these
      particles was low because of the significant contribution of the intraparticle
      EOF. Simulation results are also presented (i) for a hybrid HPLC-CEC system, and
      (ii) for different CEC systems involving open capillaries as well as packed
      columns having non-porous or porous particles. The analysis of the results
      indicates (a) the reasons for the superior performance exhibited by the hybrid
      HPLC-CEC system over the performance obtained when the system is operated only in
      the HPLC mode, and (b) the operational configuration and the properties that the
      structure of the porous particles would have to have in CEC systems involving
      uncharged or charged analytes under unretained or retained conditions in order to
      obtain high CEC efficiency (low values of the plate height, H).

PMID- 12498278
TI  - Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath
      test, suggesting bacterial overgrowth.
AB  - We have recently described an association between irritable bowel syndrome (IBS)
      and abnormal lactulose breath test, suggesting small intestinal bacterial
      overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is
      unknown. In this case-control study we evaluate the role of small intestinal
      motility in subjects with IBS and SIBO. Small intestinal motility was studied in
      consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic
      placement of an eight-channel water-perfused manometry catheter, 4-hr fasting
      recordings were obtained. Based on this, the number and duration of phase III was
      compared to 30 control subjects. To test whether there was a relationship between
      the motility abnormalities seen and the SIBO status of the patient at the time of
      the motility, subjects with a breath test within 5 days of the antroduodenal
      manometry were also compared. Sixty-eight subjects with IBS and SIBO were
      compared to controls. The number of phase III events was 0.7 +/- 0.8 in IBS
      subjects and 2.2 +/- 1.0 in controls (P < 0.000001). The duration of phase III
      was 305 +/- 123 sec in IBS subjects and 428 +/- 173 in controls (P < 0.001).
      Subjects whose SIBO was still present at the time of manometry had less frequent
      phase III events than subjects with eradicated overgrowth (P < 0.05). In
      conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of
      bacterial overgrowth seems to result in some normalization of motility.

PMID- 12498279
TI  - Appearance of peristaltic reflex in isolated guinea pig ileum in response to
      boluses of air, water, oil, and cellulose.
AB  - Distension of an isolated preparation of guinea pig ileum triggers the
      peristaltic reflex, a characteristic movement of the intestinal walls which
      generates luminal pressures and clearance of luminal contents. To determine how
      the reflex responds to properties of luminal contents, we compared the responses
      triggered by boluses of air, oil, and cellulose to boluses of Krebs' solution. We
      found that oil and cellulose increased pressures and contraction length and
      decreased outflow. Cellulose, but not oil, slowed the velocity with which the
      contraction propagated and increased the delay with which the end point (upstream
      edge) of the contraction started to propagate after the lead point (downstream
      edge). Air tended to produce short contraction segments and high velocity. We
      conclude that bolus properties such as viscosity determine the response that
      isolated intestinal segments generate to distension. Response patterns are
      reflected in contraction length, propagation velocity, and other visual
      parameters that define wall movements.

PMID- 12498280
TI  - Effects of seirogan (wood creosote) on propulsive colonic motility and stool
      characteristics in ambulatory mini-pigs.
AB  - Our goal was to determine whether Seirogan, an herbal medicine used as an
      antidiarrheal agent, modifies colonic function, including motility. Experiments
      were performed on four female Yucatan mini-pigs with established permanent cecal
      fistulas providing direct access to the colon. Long-term recordings of proximal
      colonic motility were accomplished by a solid-state probe (six pressure ports 10
      cm apart), and a motility index was calculated. Stool viscosity was also
      measured. The laxative bisacodyl (15 mg/kg) was used to induce colonic motility
      (increase in motility index) and stool softening, prior to investigating the
      effect of Seirogan (2-15 mg/kg per os twice a day) or a vehicle control. Seirogan
      (15 mg/kg), but not the placebo, reversed the bisacodyl-induced stool softening
      and restored the motility index to normal values by reducing the number of
      propagating contractions. Taken together the results suggest that inhibition of
      proximal colonic motility by Seirogan may contribute to its antidiarrheal action.

PMID- 12498281
TI  - Extrinsic neural regulation of antroduodenal motor activity in preterm infants.
AB  - This study was designed to assess whether extrinsic neural regulation of
      antroduodenal motor function is present in preterm neonates. Antroduodenal motor
      patterns were recorded in 48 infants during fasting and after a 10 ml/kg/15 min
      orograstric feeding. Plasma concentrations of pancreatic polypeptide were
      determined before and after each feeding. Of 48 infants, 24 had adult like
      duodenal motor responses to feeding, and they released pancreatic polypeptide
      postprandially. When 18 of these 24 infants were given atropine, their heart
      rates increased. Feedings, however, now failed to trigger adultlike duodenal
      motor responses or postprandial release of pancreatic polypeptide. Those 24
      infants who lacked adultlike responses failed to release pancreatic polypeptide
      postprandially. When a subset of 10 of these infants was given atropine, feedings
      failed to trigger adultlike motor responses or release of pancreatic polypeptide.
      We conclude that extrinsic neural regulation of duodenal motor patterns is
      present in only about half of preterm infants.

PMID- 12498282
TI  - Inflammatory causes of gastroparesis: report of five cases.

PMID- 12498283
TI  - Can quantitative tests of liver function discriminate between different
      etiologies of liver cirrhosis?
AB  - Studies comparing quantitative testing of liver function (QTLF) in large numbers
      of patients with defined etiology of cirrhosis are lacking. In all 316 patients
      with proven cirrhosis underwent QTLF, including aminopyrine breath test (ABT),
      galactose elimination capacity (GEC), sorbitol (SCI), and indocyanine green
      clearance (ICG). Values were correlated with the Child-Pugh classification (CP)
      and the etiology of liver cirrhosis. Fifty-five percent of the patients had
      alcoholic cirrhosis (ALC), 31% cirrhosis due to viral hepatitis (VIC), and 14%
      primary biliary cirrhosis (PBC). In all three groups there was a decrease of QTLF
      levels from CP grade A to C, which differed from normal values. QTLF was most
      compromised in patients with ALC and VIC compared to patients with PBC. In
      conclusion, QTLF in ALC and VIC patients was more reduced than in patients with
      PBC. This may be due to saturation of enzymes in ALC and ongoing inflammation in
      VIC.

PMID- 12498285
TI  - Fatal spontaneous gallbladder variceal bleeding in a patient with alcoholic
      cirrhosis.
AB  - Gallbladder varices are unusual ectopic varices that may develop in patients with
      portal hypertension, particularly in those with portal vein occlusion. In rare
      instances, these varices may cause hemobilia, life-threatening bleeding, or even
      rupture of the gallbladder. We report the first case of a 41-year-old man with
      alcoholic cirrhosis and patent portal vein who developed massive hemoperitoneum
      from spontaneous rupture of varices in the gallbladder fossa. The diagnosis of
      gallbladder varices eluded conventional imaging and was made only at autopsy.
      Gallbladder variceal hemorrhage is a rare, but potentially catastrophic
      complication of cirrhosis.

PMID- 12498284
TI  - Assessment of fatigue in patients with chronic hepatitis C using the Fatigue
      Impact Scale.
AB  - The aim of this study was to assess the impact of fatigue on the quality of life
      of patients with chronic hepatitis C (CHC) and to examine its relationship with
      various parameters of the disease, including viral load. The Fatigue Impact Scale
      (FIS), a self-report questionnaire, was applied to 92 patients with CHC, and the
      results were compared to those of an age-matched cohort of 213 healthy blood
      donors. Fatigue was frequent and disabling, being present in 67% of CHC patients,
      and the FIS was significantly increased in CHC patients compared to the healthy
      controls. Fatigue severity was not correlated with the activity of the disease or
      with the level of viremia. The FIS proved to be a valuable tool to assess this
      symptom. It should be of help for better evaluation of the clinical spectrum of
      the disease and should be included in trials assessing the efficacy of
      therapeutic interventions.

PMID- 12498286
TI  - Normalization of markedly elevated alpha-fetoprotein in a virologic nonresponder
      with HCV-related cirrhosis.
AB  - Measurement of serum AFP can be useful in the diagnosis of hepatocellular
      carcinoma (HCC). AFP is a fetal protein that is not normally present in the serum
      of adults but is elevated in most patients with HCC. The diagnosis of HCC is
      generally made in patients with a mass lesion in a cirrhotic liver if the AFP is
      over 400 ng/ml. Unfortunately, AFP is elevated in other conditions such as
      nonseminomatous germ cell tumor, chronic hepatitis, cirrhosis, pregnancy, and
      hepatic metastasis. A high AFP cutoff value for HCC would increase the
      specificity of the test, but would decrease the sensitivity considerably. We
      report the case of a patient with HCV and cirrhosis with a markedly elevated AFP
      of 1257 ng/ml in whom no evidence of HCC could be found after a thorough
      radiologic and histologic evaluation. Despite a virologic nonresponse to IFN
      alpha2b and ribavirin therapy, there was a complete normalization of AFP.

PMID- 12498287
TI  - Evaluation of role of bile flow patterns in process of in vitro stent occlusion.
AB  - Stent placement above the sphincter of Oddi might have advantages over stent
      placement across the sphincter of Oddi in prolonging stent patency in the
      treatment for malignant obstructive jaundice. To evaluate the role of bile flow
      patterns corresponding to biliary stent positioning in the process of stent
      occlusion in an in vitro bile perfusion model, one group of polyethylene stents
      was perfused continuously and another group of stents was perfused with
      additional flushing three times a day, simulating gallbladder emptying. After 8
      weeks, the flow rates through the perfused stents were measured for evaluating
      the extent of stent occlusion indirectly. The results showed that bile flow rate
      of stents with additional flushing was significantly higher than the continuously
      perfused stents (P < or = 0.01). It was demonstrated that after 18 hr of
      perfusion, additional flushing obviously decreased bacterial adherence to stent
      when compared to continuously perfused stents. In conclusion, flushing of bile
      may decrease the build-up of substance in vitro and thus improve stent flow
      rates, for which decreasing bacterial adherence to stents may be responsible.

PMID- 12498288
TI  - Effect of lafutidine, a histamine H2-receptor antagonist, on gastric mucosal
      blood flow and duodenal HCO3- secretion in rats: relation to capsaicin-sensitive
      afferent neurons.
AB  - Lafutidine is a new type of antiulcer drug, possessing both an antisecretory
      effect, exerted via a blockade of the histamine H2 receptor, and gastroprotective
      activity, mediated by capsaicin-sensitive afferent nerves (CSN). In the present
      study, we examined the effect of lafutidine on gastric mucosal blood flow (GMBF)
      and duodenal HCO3- secretion (DAS) under basal and acid-stimulated conditions in
      rats. Under urethane anesthesia, GMBF was measured using a laser Doppler
      flowmeter in a chambered stomach before and after exposure to 20 mM taurocholate
      (TC) plus 50 mM HCl, while DAS was measured in a proximal duodenal loop before
      and after mucosal acidification (10 mM HCl for 10 min) by titrating the perfusate
      at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Lafutidine given
      intraperitoneally affected neither GMBF nor DAS under basal conditions, but
      augmented an increase in both GMBF and DAS induced by mucosal acidification.
      Although the acid-induced GMBF and DAS responses were significantly mitigated by
      both indomethacin and sensory deafferentation but not by ruthenium red (RT), the
      vanilloid receptor (VR)-1 antagonist, the responses were preserved in lafutidine
      treated animals, even in the presence of indomethacin. Both GMBF and DAS were
      significantly increased by local application of capsaicin, the responses being
      attenuated by indomethacin and RT as well as sensory deafferentation. Lafutidine
      augmented the GMBF and DAS responses to capsaicin and preserved the responses,
      even in the presence of indomethacin. Capsaicin evoked an increase in [Ca2+]i in
      rat VR1-transfected HEK293 cells, while lafutidine had no effect by itself on
      [Ca2+]i in these cells and did not affect the increase in [Ca2+]i evoked by
      capsaicin. In conclusion, these results suggest that lafutidine mimics endogenous
      effects of prostaglandins to augment the GMBF and DAS responses to acid or
      capsaicin, probably by sensitizing CSN through an unknown site other than VR1.
      The luminal H+ itself is not a ligand for the RT-sensitive site of VR1 but plays
      a modulator role in the CSN-mediated physiological responses.

PMID- 12498289
TI  - Regeneration of small intestinal mucosa after acute ischemia-reperfusion injury.
AB  - To determine whether c-Fos and c-Jun are involved in the repair of small
      intestinal mucosa after ischemia-reperfusion (I/R), we investigated the mechanism
      of regeneration following acute I/R injury in rats by evaluating changes in DNA
      synthesis, fractional synthesis rate (FSR) of proteins, and alkaline phosphatase
      (ALP) activity. Furthermore, we examined the sequential expression of c-Fos and c
      Jun using western blot analysis and immunohistochemical staining. Proliferating
      cell nuclear antigen (PCNA) labeling index (LI) demonstrated that the LI of the
      I/R group at 2 and 6 hr after reperfusion was significantly higher than that of
      the controls. Statistically significant differences were found between the FSRs
      of the I/R group and the corresponding conventional group at 2, 6, and 12 hr. The
      expression of c-Fos and c-Jun proteins increased markedly after I/R and these
      proteins decreased with time. The levels of ALP in the I/R group were
      significantly decreased at 2 and 6 hr after reperfusion compared to controls.
      These results indicate that c-Fos and c-Jun play a central role in the repair
      process that results in complete restoration of intestinal mucosal function after
      I/R.

PMID- 12498290
TI  - Asymptomatic chronic intestinal ischemia caused by idiopathic phlebosclerosis of
      mesenteric vein.
AB  - Phlebosclerosis of the mesenteric vein is a rare condition causing chronic
      intestinal ischemia, it has only been reported in Japan. A 56-year-old man with
      liver cirrhosis and hepatic tumor presented with phlebosclerosis of mesenteric
      vein without any abdominal symptoms. He was admitted for examination of suspected
      hepatic tumor. Abdominal plain x-ray films and computed tomography revealed
      calcification of the mesenteric vein. Barium enema revealed narrowing and
      thumbprinting from the cecum to transverse colon. On colonoscopic examination,
      blue-black vessels were visible in the terminal ileum, and hyperemic nodular
      mucosa with small irregular ulcers surrounded by dark purple mucosa was found
      from the cecum to transverse colon. The etiology of mesenteric vein
      phlebosclerosis is unknown, although a physical mechanism rather than
      inflammatory changes appear to be involved in this rare and usually progressive
      condition of chronic intestinal ischemia.

PMID- 12498291
TI  - Racial differences in use of colonoscopy, sigmoidoscopy, and barium enema in
      Medicare beneficiaries.
AB  - Colorectal cancer is often diagnosed at a later stage in blacks. We wanted to
      know if racial differences existed in the use of tests for detection of
      colorectal cancer. A 5% random sample was obtained of all Medicare beneficiaries
      with Part B coverage, aged 65 years and older and classified as white or black
      race. The numbers of colonoscopies, flexible sigmoidoscopies, and barium enemas
      were determined from the Physician/Supplier file. Blacks were 18% less likely to
      receive colonoscopy and 39% less likely to receive flexible sigmoidoscopy after
      controlling for age, sex, income, and access to care in a multivariable logistic
      regression model. Barium enema was not significantly different between the races.
      Black men had 25% lower use of colonoscopy and 50% decreased use of flexible
      sigmoidoscopy. Blacks receive less colonoscopy and flexible sigmoidoscopy than
      whites. Black men are particularly vulnerable to the under-use of these tests.

PMID- 12498292
TI  - Distribution of estrogen receptor subtypes, expression of their variant forms,
      and clinicopathological characteristics of human colorectal cancer.
AB  - We examined the expression of estrogen receptor (ER) messenger RNAs (ER-alpha, ER
      beta, and ER-beta isoforms) in colorectal tumor samples and corresponding normal
      mucosa, paying particular attention exons 3 and 5 of both ER mRNA subtypes that
      likely suffer deletions, and may encode proteins that have lost either DNA- or
      ligand-binding moieties. Then we correlated these findings with the
      clinicopathological properties of the tumors. Our results demonstrated that in
      all patients the two ER subtype mRNAs were coexpressed in wild-type form. In 10%
      of the patients the ER-alpha mRNA was also present as an exon-5-deleted form that
      encoded any aberrant protein. Immunohistochemical analysis revealed that the ER
      beta protein was present in tumor stroma, but not in infiltrating lymphocytes. ER
      beta1 and ER-beta2, isoforms of ER-beta, were up-regulated in malignant tissues,
      whereas the ER-beta5 isoform, was found to be equally expressed, at very low
      levels, in the two tissue compartments. No correlations between ER levels and
      clinicopathological parameters were found. This suggests that the ER-beta mRNA
      levels are independent of the tumor characteristics.

PMID- 12498293
TI  - Prohormone convertase furin has a role in gastric cancer cell proliferation with
      parathyroid hormone-related peptide in a reciprocal manner.
AB  - We investigated the expression of parathyroid hormone-related peptide (PTHrP) and
      the relationship between PTHrP and its endoprotease furin in gastric cancer.
      PTHrP was colocalized with furin in 75% of gastric cancer tissues (six of eight)
      from patients with high serum PTHrP levels. PTHrP mRNA expression was confirmed
      in 67% of gastric cancer cell lines (four of six), whereas furin mRNA was
      detected in all six gastric cancer cell lines. In a cultured gastric cancer cell
      line, MKN28, mature PTHrP protein expression was markedly increased by
      transfection of furin cDNA. Furin cDNA-transfected MKN28 cells grew faster than
      did the mock controls. Moreover, furin mRNA expression in cultured gastric cancer
      cells was enhanced when PTHrP was added to the culture medium. These results
      suggest a link between PTHrP and furin in the regulation of gastric cancer cell
      growth. Furin might be involved not only in the production of the mature form of
      PTHrP, but also in promoting growth in gastric cancer cells.

PMID- 12498294
TI  - Interrelation between expression of matrix metalloproteinase 7 and beta-catenin
      in esophageal cancer.
AB  - Matrix metalloproteinase 7 (MMP-7) may play a key role in the progression of
      various human malignant tumors. Nuclear beta-catenin enhances the activating
      expression of MMP-7 genes by binding with the T-cell factor/lymphoid enhancer
      factor family of transcription factors. We immunohistochemically examined the
      expression of MMP-7 and beta-catenin to better understand the significance of
      these factors in the progression of esophageal squamous cell carcinoma. The
      entire coding region of beta-catenin exon 3 was also analyzed by direct
      sequencing in all cases. We found that MMP-7 was expressed in 7 (20.6%) of 34
      esophageal squamous cell carcinomas. There was a significant relationship between
      MMP-7 expression and tumor invasion into adjacent structures (P < 0.05). Aberrant
      nuclear expression of beta-catenin was found in 12 of 34 (35.3%) esophageal
      cancers and correlated with MMP-7 expression, the statistical difference being (P
      < 0.05). None of the 34 esophageal cancers examined carried mutations in beta
      catenin exon 3. MMP-7 expression correlates with penetrating tumor progression in
      esophageal cancer. Nuclear translocation of beta-catenin, without mutations in
      beta-catenin exon 3, is associated with MMP-7 expression.

PMID- 12498295
TI  - Human esophageal cancer is distinguished from adjacent esophageal tissue by
      tissue cysteine concentrations.
AB  - Recent studies have suggested that cysteine, in addition to glutathione, may play
      a role in the genesis, pathobiology, and treatment response of rodent and human
      cancers. We examined the relative concentrations of cysteine and glutathione in
      human esophageal cancer and adjacent, minimally involved esophageal tissue. Small
      biopsies from tumors and adjacent esophageal tissues were placed into cold acid
      to allow extraction of low-molecular-mass compounds and simultaneous
      precipitation of macromolecules. Supernatants were analyzed by high-performance
      liquid chromatography with electrochemical detection for thiol content. While
      there was no statistically significant difference between the glutathione content
      of tumor versus adjacent tissue (2.2 mM vs 2.1 mM, respectively), tumor tissue
      had significantly higher levels of cysteine than adjacent tissue (0.21 mM vs 0.13
      mM, respectively). In conclusion, cysteine content distinguishes tumor from
      adjacent more normal tissue.

PMID- 12498296
TI  - Effect of interleukin-11 on ameliorating intestinal damage after methotrexate
      treatment of breast cancer in rats.
AB  - Gastrointestinal mucositis after cancer chemotherapy is an increasing problem
      that is essentially untreatable once established, although it gradually remits.
      The aim of this study was to investigate the time-course and effect of
      interleukin-11 (IL-11) on apoptosis and intestinal morphometry as measures of
      mucositis. Female DA rats were implanted subcutaneously with syngeneic breast
      cancer and treated with methotrexate (MTX). Intestinal morphometry was used to
      assess villus area, crypt length, and mitotic count per crypt. Apoptosis was
      assessed by TUNEL assay in the tumor and jejunum. Tumor proliferation was
      assessed by mitotic count. The time-course study showed that MTX increased
      apoptosis by 28-fold in the crypts of the small intestine and by 3-fold in the
      tumor, and peaked at 6 hr after chemotherapy. IL-11 (100 microg/kg/twice daily
      subcutaneously) maintained intestinal weight, and reduced the severity of
      mucositis, as measured by villus area, crypt length, and mitotic count per crypt.
      IL-11 at higher doses (200 microg and 400 microg/kg/twice daily subcutaneously),
      did not further improve villus area, crypt length, and mitotic count per crypt.
      IL-11 did not affect tumor apoptosis or proliferation. We conclude that IL-11
      attenuated mucositis by maintaining intestinal weight and morphometry. IL-11 did
      not prevent apoptosis, but rather induced compensatory crypt cell proliferation.

PMID- 12498297
TI  - Adenocarcinoma within a diverticulum: a common tumor arising in an uncommon
      location.

PMID- 12498298
TI  - Adenocarcinoid of the appendix vermiformis: complete and persistent remission
      after chemotherapy (folfox) of a metastatic case.
AB  - A 58-year-old woman underwent surgery for a pelvic mass. Palliative resection was
      performed despite the presence of multiple retroperitoneal lymph nodes. All
      pathology specimens exhibited an adenocarcinomatous component associated with
      carcinoid proliferation related to an appendicular tumor leading to the diagnosis
      of appendicular adenocarcinoid with ovarian, peritoneal, and nodal metastases.
      The patient's general status worsened rapidly with widespread nodal metastasis.
      Chemotherapy (Folfox 4 regimen) was given, and the patient improved within six
      weeks. Complete response was achieved after three months. Presently, more than
      three years after the end of the treatment, the patient is still alive and in
      complete remission. Appendicular adenocarcinoid is exceptional. These tumors
      exhibit two cellular components. Ovarian metastasis is frequent. Prognosis is
      intermediate between adenocarcinoma and malignant carcinoid. When given to
      patients with colonic carcinoma, the Folfox regimen used effectively here, is
      associated with a 50% objective response but complete response is very
      exceptional.

PMID- 12498299
TI  - An open-label trial of theophylline for functional chest pain.
AB  - Visceral hypersensitivity may play a role in the pathogenesis of functional chest
      pain, although the underlying mechanism(s) is unknown. We investigated the
      effects of theophylline, an adenosine receptor antagonist, on sensory perception
      and biomechanical properties of esophagus in patients with functional chest pain.
      Esophageal balloon distention was performed using impedance planimetry in 21
      consecutive patients with functional chest pain. Patients found to have a
      hypersensitive esophagus received intravenous theophylline and balloon distension
      was repeated. If the hypersensitivity improved, oral theophylline was prescribed
      for three months as an open label trial. Balloon distension reproduced typical
      chest pain in 16 (76%) patients at thresholds suggestive of hypersensitivity.
      After theophylline infusion, pain thresholds increased in 12 (75%) patients.
      Median threshold pressures for discomfort and pain improved (P < 0.01). Cross
      sectional area increased (P < 0.05) and the tension/strain association shifted to
      the right (P < 0.01). Seven of eight patients reported sustained improvement in
      pain after oral theophylline. Theophylline may ameliorate chest pain in patients
      with hypersensitive esophagus, possibly by altering adenosine-mediated
      nociception.

PMID- 12498300
TI  - Gastric bilirubin monitoring to assess duodenogastric reflux.
AB  - Duodenogastric reflux (DGR) was assessed with 24-hour gastric bilirubin
      monitoring in 345 patients (219 men; 49 +/- 13 years) with foregut symptoms and
      41 healthy subjects (24 men, 28 +/- 5 years). Bilirubin exposure was measured as
      percent time above absorbance level 0.25 and excessive DGR was defined above the
      95th percentile of normal values (>24.8%). DGR was highest following Billroth II
      gastric resection (60 +/- 24%, N = 15). Patients after cholecystectomy (28 +/-
      25%, N = 25), patients with gastroesophageal reflux disease (24 +/- 24%, N =
      199), and patients with nonulcer dyspepsia (23 +/- 21%, N = 61) had a
      significantly higher exposure to DGR than healthy subjects (7 +/- 8%, P <
      0.0001). In conclusion, gastric bilirubin monitoring is useful for the assessment
      of DGR specifically in symptomatic patients following gastric resection.
      Increased amounts of DGR may further be of clinical importance in patients with
      reflux disease or nonulcer dyspepsia and following cholecystectomy.

PMID- 12498301
TI  - Differences in gastroprotective processes in 6- to 8- and 14- to 16-week-old
      rats.
AB  - The gastroprotective effect of opioid peptides, prostaglandin E2 and capsaicin
      against acidified ethanol-induced gastric mucosal damage in young mature rats of
      different (6-8 and 14-16 weeks) ages has been investigated. It was found that
      gastric mucosal damage was more severe in 14-16 weeks old rats. The
      gastroprotective effect of opioid peptides--[D-Ala2, D-Leu5]-enkephalin (DADLE),
      deltorphin II, [D-Ala2, Phe4, Gly5 -ol]-enkephalin (DAGO) and beta-endorphin-
      given either intracerebroventricularly (0.6, 3.3, 0.2, and 0.01 nmol/rat,
      respectively) or subcutaneously (825 and 960 nmol/kg, respectively) was highly
      reduced in 14-16 weeks old rats. The mucosal protective action of orally
      administered capsaicin (1600-3200 nmol/kg) and PGE2 (280-560 nmol/kg) was also
      diminished in 14-16 weeks old animals. Both ACTH and corticosterone plasma levels
      were significantly higher in 14-16 weeks old rats. These results suggest that the
      gastric mucosal susceptibility to ethanol and the gastroprotective effect of
      opioid peptides, capsaicin and PGE2 are age-related.

PMID- 12498302
TI  - Extra-virgin olive oil-enriched diets reduce indomethacin-induced gastric
      oxidative damage in rats.
AB  - Olive oil, the main fat component of the Mediterranean diet, has been found to be
      protective against oxidative stress and could be beneficial in inflammatory and
      gastrointestinal disorders. First-pressed, extra-virgin olive oil (EVOO) has
      appreciable amounts of powerful antioxidants such as polyphenolic compounds that
      prevent its autoxidation and are responsible for its high stability. The aim of
      the present study was to determine whether diets supplemented with EVOO could
      reduce the severity of indomethacin-induced gastric oxidative damage and also to
      study changes in the activities of certain oxidative stress-related enzymes such
      as xanthine oxidase, myeloperoxidase as a marker of neutrophil infiltration, and
      the antioxidant enzyme superoxide dismutase. Lipid peroxidation and possible
      modifications in gluthatione metabolism were also studied. Weanling rats were
      maintained on semisynthetic diet for 6 weeks; a standard diet containing 5% (w/w)
      of fat as control or EVOO supplemented diets (5% and 20% w/w). Gastric lesions
      were induced on the last day by oral administration of indomethacin (60 mg/kg
      body wt). In animals fed EVOO diets, gastric lesions were decreased significantly
      and in parallel with dietary fat, when compared to animals consuming a standard
      diet. These protective effects were related to a reduction of lipid peroxides
      generation, neutrophil infiltration, and xanthine oxidase activity. Superoxide
      dismutase, an important enzyme to scavenger of lipid peroxides, was unaffected by
      feeding conditions. On the other hand, dietary supplementation with EVOO
      significantly increased both glutathione peroxidase activity and total
      glutathione content. In conclusion, this study provides evidence that fat diets
      containing EVOO reduces indomethacin-induced gastric damage in rats. This effect
      may be partly due not only to reducing oxidative stress and neutrophil-induced
      toxicity but also to enhancing the glutathione antioxidant defense system.

PMID- 12498303
TI  - Gastrointestinal tolerability of metamizol, acetaminophen, and diclofenac in
      subchronic treatment in rats.
AB  - The gastrointestinal tolerability of metamizol and acetaminophen [weak
      cyclooxygenase (COX) inhibitors] in comparison with diclofenac (nonselective
      cyclooxygenase inhibitor) was evaluated in subchronic treatments in rats. Wistar
      rats received 60 mg/kg body weight of metamizol and acetaminophen, and 3 mg/kg
      body weight of diclofenac by oral route twice daily for 14 days. Myeloperoxidase
      activity, an index of neutrophil infiltration, COX expression and the effects on
      blood parameters used as indicators of liver and renal functions were also
      studied. Metamizol and acetaminophen did not cause apparent gastrointestinal
      lesions; in contrast diclofenac showed swelling and an increased thickness on the
      distal intestinal mucosa. Myeloperoxidase activity was significantly increased in
      the small bowel with diclofenac treatment. In gastric mucosa the expression of
      the cyclooxygenase-1 was not affected and the expression of cyclooxygenase-2 was
      not observed. Diclofenac treatment significantly diminished hematocrit,
      hemoglobin, and corpuscular volume and increased the number of platelets.
      Aspartate aminotransferase and gamma-glutamyltransferase activity were also
      altered and, regarding the renal biochemical parameters, the animals treated with
      diclofenac had increased urea values. In contrast, acetaminophen treatment did
      not affect either of these parameters and metamizol increased only the alanine
      aminotransferase activity. Under our experimental conditions, metamizol and
      acetaminophen seem to be safe drugs. In contrast, with diclofenac treatment blood
      loss and anemia are observed which could stem from the small intestinal injury.
      Moreover, this drug could to impair kidney function.

PMID- 12498304
TI  - Induction of a 72-kDa heat-shock protein in cultured rat gastric mucosal cells
      and rat gastric mucosa by zinc L-carnosine.
AB  - An antiulcer drug, zinc L-carnosine (polaprezinc), provides gastric mucosal
      protection against various irritants. In this study, we evaluated the effects of
      zinc L-carnosine on expression of 72-kDa heat shock protein (HSP72, stress
      inducible HSP70), which is known as an endogenous cytoprotectant in a wide
      variety of cells, including rat gastric mucosa in vitro and in vivo. Expression
      of HSP72 after exposure to zinc L-carnosine, zinc sulfate, or L-carnosine (1-300
      microM) in rat gastric mucosal cells (RGM1) and intragastric administration of
      zinc L-carnosine, zinc sulfate (30 or 100 mg/kg) and L-carnosine (76 mg/kg) was
      investigated by western blotting and densitometric analysis. Exposure to zinc L
      carnosine and zinc sulfate increased the expression of HSP72 significantly in
      RGM1 cells. Intragastric administration of zinc L-carnosine and zinc sulfate
      showed significant increment in HSP72 in rat gastric mucosa also in vivo. The
      ability to induce HSP72 is significantly higher in zinc L-carnosine compared with
      zinc sulfate based on molecular concentration in vivo. However, L-carnosine did
      not increase the expression of HSP72 in vitro and in vivo. Zinc derivatives,
      especially zinc L-carnosine, could be a strong HSP72 (chaperon) inducer, which
      has been known to enhance mucosal protective ability.

PMID- 12498305
TI  - Clinical features of patients with novel Yersinia species.
AB  - Our purpose was to describe the clinical features of patients with novel Yersinia
      species. Between 1985 and 1999; 194 patients had yersinia species isolated from
      stool specimens, 38 (20%) had non-Yersinia enterocolitica species; 12 (32%) had
      Yersinia intermedia, 7 (18%) Yersinia fredericksenii, 3 (8%) Yersinia
      kristensenii, and the remaining 16 (42%) were unclassified non-Yersinia
      enterocolitica species. The most common presenting symptom was diarrhea alone in
      10 (26.3%) patients. Symptoms persisted for >1 month in 54% of cases; 21% had
      symptoms for <1 week; 18 (47%) patients were taking corticosteroids, acid
      suppressants, and/or antibiotics when Yersinia was isolated. An immunocompromised
      state was present in 11 (29%) patients. An immunocompromised host and
      administration of acid suppressants predicted persistence of symptoms for >1
      month. Most [27 (71%)] patients received no treatment; 5 (13%) received
      antibiotics. In conclusion, novel non-Yersinia enterocolitica species, including
      Yersinia intermedia, Y. fredericksenii, and Y. kristensenii may represent up to
      20% of all Yersinia isolates. Diarrhea is the most common symptom.

PMID- 12498307
TI  - Radiation-induced crypt intestinal epithelial cell apoptosis in vivo involves
      both caspase-3-dependent and -independent pathways.
AB  - Caspases play a major role in virtually all forms of apoptosis. Radiation is well
      known to induce apoptosis of crypt intestinal epithelial cells (IEC). Here, we
      examined the role of caspase-3 in radiation-induced IEC apoptosis. We demonstrate
      that while caspase-3 is present in IEC and activated upon irradiation, IEC in
      caspase-3-deficient mice partially underwent radiation-induced apoptosis. Typical
      morphological changes of IEC undergoing radiation-induced apoptosis (ie,
      blebbing, shrinkage, and nuclear condensation) can occur independently of caspase
      3; however DNA fragmentation, as analyzed by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL) staining, is mostly, but not
      entirely, caspase-3-dependent. Overall, these results demonstrate that radiation
      induced crypt IEC apoptosis has both caspase-3-independent and -dependent
      components.

PMID- 12498306
TI  - Diminished efficacy of colonic adaptation to lactulose occurs in patients with
      inflammatory bowel disease in remission.
AB  - Lactulose has been proposed to be beneficial in treating inflammatory bowel
      disease (IBD). The hypothesis is based on the prebiotic potential of lactulose. A
      practical approach to testing its usefulness is to determine colonic adaptation
      to tolerable doses in patients with IBD. Our objective was to determine if a 3
      week course of lactulose will decrease BH2 and symptoms in response to an acute
      lactulose challenge test in control subjects and IBD patients. The design was a
      prospective cohort study. Subjects were given a 30-g lactulose challenge test
      (test 1), and then ingested 10 g of lactulose twice a day for 3 weeks before
      being retested (Test 2). A third test was given after a further 5-week washout
      period. The main outcomes were the change in 4-hr sum of BH2 (sum(4HrBH2)) values
      obtained every 30 min, peak BH2, and 4-hr sum of symptom score (sum(4HrSS))
      during the lactulose challenge test. In addition, we also report the change in
      self-reported symptoms and diarrhea during the 3-week administration of
      lactulose. In controls, sum(4HrBH2) decreased from test 1 (380.5 +/- 56.6 ppm) to
      test 2 (288.6 +/- 57.4 ppm) (P < 0.05), and returned toward test 1 levels by test
      3 (307.5 +/- 53.1, P > 0.5). Unlike controls, the sum(4HrBH2) in patients failed
      to achieve significance between test 1 (444.5 +/- 55.8 ppm), test 2 (366.5 +/-
      80.7 ppm, P > 0.2) or test 3 (411.6 +/- 62.5 ppm, P > 0.2). Sum(4HrSS) results in
      controls followed a pattern similar to sum(4HrBH2), achieving significance only
      in test 2 (P < 0.02). Symptoms during the intertest periods decreased by the
      third week in controls (P < 0.05), but not in patients (P > 0.5). Symptoms were
      lower in patients and varied insignificantly both in challenges and intertest
      periods. In conclusion, although controls adapt to a 3-week period of lactulose
      ingestion, IBD patients fail to meet the criteria for adaptation. However, longer
      studies may be needed to establish whether IBD patients are slower to adapt.

PMID- 12498309
TI  - Effects of octreotide acetate and Saccharomyces boulardii on bacterial
      translocation in an experimental intestinal loop obstruction model of rats.
AB  - Intestinal obstruction (IO) induces bacterial translocation (BT) due to mucosal
      disruption, motility dysfunction, and increased intestinal volume, leading to
      bacterial overgrowth. This study was conducted to investigate the effects of
      octreotide acetate (OA) and Saccharomyces boulardii (SB) on the BT and intestinal
      integrity in an animal model of intestinal loop obstruction (LO). Forty adult
      male Sprague-Dawley rats (250-300 g) were randomized into 4 groups containing 10
      rats each. Complete IO was created in the distal ileum of rats by a single 3-0
      silk suture (LO). Group Sham: Sham (Laparotomy only was performed in this group);
      group LO: LO; group OA: LO plus OA (100 microg/kg, at 0, 12 hours of
      obstruction); group (SB): LO plus SB (800 mg/kg/day, via orogastric and
      preoperative for 3 days). After 24 hours, samples of mesenteric lymph nodes
      (MLN), liver, spleen and blood were obtained and cultured. The terminal ileum
      specimens were examined histopathologically. There were no BT in group Sham, but
      BT was noticed totally in 31 (77.5%) cultures in group LO. This rate was reduced
      to 30% (n = 12), 10% (n = 4) in the groups OA and SB respectively. Bacterial
      translocations of MLN and the liver in group LO were significantly higher than
      those of groups OA and SB. Bacterial translocations of the both spleen and blood
      in group LO were significantly higher than those of groups OA and SB. The mean
      bacterial counts, colony-forming units per gram tissue (cfu/g), in the MLN, liver
      and spleen of group LO were found significantly higher than those of groups OA
      and SB. The mean villus height in group OA was significantly higher than that of
      group LO and it in the group SB significantly higher than those of groups LO and
      OA. The present experimental study has demonstrated that OA and SB may have
      protective effects against BT in mechanical bowel obstruction and additionally SB
      preserves intestinal mucosal integrity.

PMID- 12498308
TI  - Development of a vitamin D-responsive organ culture system for adult and old rat
      intestine.
AB  - The purpose of this study was to develop an organ culture system for adult and
      old rat small intestine that is responsive to vitamin D. Explants from F344 rats
      were cultured on Millipore tissue culture inserts placed in 6-well dishes at a
      temperature of 28 degrees C and in the presence of 95% oxygen. Explants from
      young (2 months old), adult (12 months old), and old (22 months old) rats were
      viable for up to 12 hr as determined by constant rates of DNA and protein
      synthesis. Hormonal responsiveness was characterized by measuring the capacity of
      1,25-dihydroxyvitamin D [1,25(OH)2D], the hormonal form of vitamin D, to increase
      mRNA levels of the intestinal 24-hydroxylase cytochrome P-450 (CYP24). Jejunal
      explants from young rats increased CYP24 mRNA levels in a linear fashion with an
      EC50 of 3 nM in response to 1,25(OH)2D. There was no change with age in the
      magnitude of the jejunal response with regard to time (0-12 hr) or dose (0.1-100
      nM). However, in the duodenum, 1,25(OH)2D increased CYP24 mRNA to significantly
      higher levels in the adult compared to the young. Since the 24-hydroxylase is the
      first step in the degradative pathway for 1,25(OH)2D in the intestine, increased
      duodenal expression of the 24-hydroxylase may contribute to the decreased action
      of 1,25(OH)2D on the adult duodenum.

PMID- 12498310
TI  - Micronucleus evaluation in mitogen-stimulated lymphocytes of PUVA treated
      patients.
AB  - PUVA describes the treatment of patients with psoralens plus an exposure to a
      source of UV light of 320-400 nm (UVA). Contradictory results have been reported
      on the chromosomal damage of PUVA when assayed by sister chromatid exchange (SCE)
      method. Micronucleus (MN) test is used to detect both clastogenic (breaking) and
      aneugenic (abnormal segregation) effect of physical/chemical agents on the
      chromosomes. No data have been found on the MN formation in the cells of PUVA
      treated patients. Frequency of micronuclei in 72 hours cultivated/mitogen
      stimulated lymphocytes of patients have been evaluated at zero time and after 20,
      40, 60 sessions of PUVA treatment. While the beginning MN frequency was
      approximately 0.22% (n=23), it raised to approximately 0.32 (n=23), approximately
      0.42 (n=14) and approximately 0.53% (n=10) corresponding respectively to 20, 40
      and 60 sessions. These sessions correspond reciprocally to 54+/-23, 172+/-48,
      300+/-61 joules/cm2 of UVA and 13, 26, 39 mg/kg of 8-metoxypsoralen (8-MOP).
      While large interindividual variances were apparent, highly significant
      differences have been observed between initial MN frequency and after that of the
      20, 40 and 60 sessions, (p = 0.000, p = 0.004, p = 0.005, reciprocally, Wilcoxon
      two-related samples test). The coefficient of correlation between MN frequency
      and UVA doses starting from zero to 60 sessions of treatment has been found as r
      = 0.61. This indicates a significant relationship between UVA doses and MN
      frequencies. However, MN inducibility and synergistic property of 8-MOP with UVA
      should be taken into account. Gradual MN increase during different sessions of
      PUVA treatment shows that--once appeared--a part of MN at least persist in the
      cells of patients from a few days to a few weeks. Smoking as a confounding factor
      seems to increase MN frequency (p = 0.053, Mann-Whitney U-test) in the beginning
      population, taken as the control population. This is the first report on the
      kinetics of MN formation during different sessions of PUVA treatment. Based on
      our results, we concluded that PUVA treatment causes a detectable chromosome
      damaging effect on the relatively profound cells/tissues of its human users.
      Therapists should be careful with its use, especially on the patients who may be
      more susceptible to carcinogenesis (e.g. immunosuppressed and/or elderly
      subjects).

PMID- 12498311
TI  - Recombinant human interleukin-1alpha increases serum albumin, Gc-globulin, and
      alpha1-antitrypsin levels in burned mice.
AB  - The response to thermal injury is a complex physiologic process requiring
      communication between sites of injury and distant target organs. The liver, one
      of these target organs, synthesizes a family of secretory proteins, the acute
      phase proteins, that carries out specific immunoprotective functions. In this
      study we investigated the effects of daily recombinant human interleukin-1alpha
      (rhIL-1alpha) administration on the serum levels of negatively regulated, i.e.,
      albumin and Gc-globulin and positively regulated, i.e., alpha1-antitrypsin, acute
      phase proteins in a murine model of thermal injury. Adult CF-1 female mice
      underwent a 6.5-seconds, 20% total burn surface area, full thickness steam
      injury, and received either intraperitoneal rhIL-1alpha (20 microg x kg(-1) x
      day(-1)) or diluent for 10 days. Seven and 14 days after injury, mice were
      sacrificed, and serum albumin, Gc-globulin and alpha1-antitrypsin levels were
      measured by crossed immunoelectrophoresis technique. Thermal injury significantly
      lowered serum albumin levels, tended to decrease Gc-globulin levels, and
      increased serum alpha1-antitrypsin levels. Daily rhIL-1alpha administration after
      burn injury prevented hypoalbuminemia, and increased serum levels of Gc-globulin
      and alpha1-antitrypsin. IL-1 therapy might be helpful to maintain the homeostasis
      and immunity of the host after thermal injury.

PMID- 12498312
TI  - Marked increase in urinary bicarbonate and pH caused by heavy muscular exercise
      with dynamic knee extension.
AB  - In order to estimate the physiological responses to heavy muscular exercise with
      dynamic knee extension, the levels of urinary variables such as bicarbonate,
      urinary pH and blood lactate were studied before and after the exercise. Nine
      male volleyball players aged 19 or 20 years were involved in the present study.
      They performed 10%, 30% and 80% 1 repetition maximum (RM) knee extension. The
      levels of urinary bicarbonate and urinary pH did not change for 2.5 hours after
      cessation of the exercise with 10% 1 RM load, compared with the baseline levels.
      When 30% 1 RM loading was given, urinary bicarbonate and pH moderately increased
      for 2.5 hours. When 80% 1 RM loading was given, both urinary bicarbonate and pH
      increased immediately after cessation of the exercise, for 2.5 hours. Levels of
      blood lactate increased extensively within 1 minute after cessation of the
      exercise in the subjects with 80% 1 RM load, but no significant increase was seen
      in subjects with 10% 1 RM load. The changes in urinary bicarbonate and pH could
      be explained by the continuous production of CO2 in the muscular tissues involved
      in the exercise with a submaximal load where excess postexercise oxygen
      consumption is accelerated. It is also possible that the liver and muscle where
      blood lactate is aerobically metabolized could be the cause of these changes. It
      was also suggested that the measurement of urinary bicarbonate and pH may be
      useful for the estimation of events in the body after submaximal exercise
      loading.

PMID- 12498313
TI  - A case of solitary fibrous tumor of the parotid gland: review of the literatures.
AB  - We report a rare case of solitary fibrous tumor of the parotid gland. A 47-year
      old woman presented with a 3-year-history of left-sided subauricular swelling.
      Computed tomographic scans and magnetic resonance images revealed a well-defined
      and dumbbell-shaped mass, measuring about 30 mm in its greatest dimension, in the
      left parotid gland. Because the tumor occupied both superficial and deep lobes of
      the gland, she underwent total parotidectomy with preservation of the facial
      nerve. The microscopic finding showed short-spindle and ovoid cells arranged in a
      haphazard pattern with interspersed thin collagen fibrils. Immunohistochemically,
      the tumor cells were strongly positive for CD34, bcl-2 and vimentin, whereas
      stains for S-100, cytokeratin, smooth muscle actin, collagen type IV and CD117
      (KIT) were negative. On the basis of these findings, the tumor was diagnosed as
      solitary fibrous tumor. Her post-operative course was uneventful, and she is
      currently free from disease 14 months after surgery. Diagnosis, clinical behavior
      and treatment of solitary fibrous tumor are reviewed from perusal of the
      literature.

PMID- 12498314
TI  - The effect of vitamin E treatment on oxidative stress generated in trained rats.
AB  - The aim of this study was to investigate the effect of vitamin E treatment on
      increased oxidative stress in rats exposed to a swimming exercise protocol. In
      order to examine the effects of physical swimming training on the antioxidant
      defences of tissues and on their susceptibility to damage induced by exercise,
      the levels of glutathione (GSH) and thiobarbituric acid reacting substances
      (TBARS) levels, on indicator of lipid peroxidation in various tissues, have been
      determined. In this study, four groups of female rats were used while the rats
      were trained to swim for 30 minutes a day and five days a week which lasted eight
      weeks and vitamin E (vit. E) supplementation (30 mg/kg/day) has been carried out
      for five days a week. TBARS levels are significantly found lower in both trained
      and sedentary vit. E supplemented groups, since vit. E is the most important
      antioxidant in an earlier line of defence in lipid peroxidation. Also, in vit. E
      supplemented trained rats, the glutathione response is observed to be
      significantly higher, supporting with the TBARS levels and in accordance with the
      literature. But in the sedentary group without vit. E supplementation, the GSH
      levels of the liver and the heart tissues were significantly lower than both vit.
      E supplemented sedentary and trained groups. These results evaluate that vit. E
      confers protection to GSH levels in these tissues where the GSH levels were found
      significantly lower in the groups not supplemented with vit. E.

PMID- 12498315
TI  - Establishment and characterization of a simian virus 40-immortalized rat
      pancreatic stellate cell line.
AB  - Activated pancreatic stellate cells (PSCs) have recently been implicated in the
      pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be
      subcultured only several times because of their limited growth potential. A
      continuous cell line would be valuable in studying molecular mechanisms of these
      pancreatic disorders. The aim of this study was to establish an immortalized cell
      line of rat PSCs. PSCs were isolated from the pancreas of male Wistar rats, and
      the simian virus 40 T antigen was introduced to PSCs by retrovirus-mediated gene
      transfer. This procedure yielded an actively growing cell line, designated as SAM
      K. This cell line has been passaged repeatedly for almost 2 years, and is thus
      likely immortalized. SAM-K cells retained morphological characteristics of
      primary PSCs, and expressed alpha-smooth muscle actin, glial fibrillary acidic
      protein, type I collagen, fibronectin, and prolyl hydroxylases. The level of p53
      expression was very high in SAM-K cells. Proliferation of SAM-K cells was
      stimulated by serum and platelet-derived growth factor-BB. Interleukin-1beta (IL
      1beta) activated nuclear factor-kappaB, activator protein-1, and three classes of
      mitogen-activated protein (MAP) kinases: extracellular signal-regulated
      kinase1/2, c-Jun N-terminal kinase, and p38 MAP kinase. IL-1beta induced
      expression of intercellular adhesion molecule-1 and monocyte chemoattractant
      protein-1, both of which were abolished in the presence of pyrrolidine
      dithiocarbamate, a specific inhibitor of nuclear factor-kappaB activation. IL
      1beta-induced monocyte chemoattractant protein-1 was partially inhibited by
      specific inhibitors of MAP kinase kinase (U0126) and of p38 MAP kinase (SB203580)
      whereas intercellular adhesion molecule-1 expression was not altered by the
      inhibitors. Thus, SAM-K would be useful for in vitro studies of cell biology and
      signal transduction of PSCs.

PMID- 12498316
TI  - Lead, chemical porphyria, and heme as a biological mediator.
AB  - One of the most well-characterized symptoms of lead poisoning is porphyria. The
      biochemical signs of lead intoxication related to porphyria are delta
      aminolevulinic aciduria, coproporphyrinuria, and accumulation of free and zinc
      protoporphyrin in erythrocytes. From the 1970s to the early 80s, almost all of
      the enzymes in the heme pathway had been purified and characterized, and it was
      demonstrated that delta-aminolevulinic aciduria is due to inhibition of delta
      aminolevulinate dehydratase by lead. Lead also inhibits purified ferrochelatase;
      however, the magnitude of inhibition was essentially nil even under pathological
      conditions. Further study proved the disturbance of iron-reducing activity by
      moderate lead exposure. Far different from these two enzymes, lead failed to
      inhibit purified coproporphyrinogen oxidase, i.e., the mechanism of
      coproporphyrinuria has not yet been understood. During the 80s to the 90s, the
      effects of environmental hazards including lead were elucidated through stress
      proteins, indicating the induction of some heme pathway enzymes as stress
      proteins. At that time, gene environment interaction was another focus of
      toxicology, since gene carriers of porphyrias are considered to be a high-risk
      group to chemical pollutants. Toxicological studies from the 70s to the 90s
      focused on the direct effect of hazards on biological molecules, such as the heme
      pathway enzymes, and many environmental pollutants were proved to affect
      cytosolic heme. Recently, we demonstrated the mechanism of the heme-controlled
      transcription system, which suggests that the indirect effects of environmental
      hazards are also important for elucidating toxicity, i.e., the hazards can affect
      cell functions through such biological mediators as regulatory heme. It is,
      therefore, probable that toxicology in the future will focus on biological
      systems such as gene regulation and signal transduction systems.

PMID- 12498317
TI  - Investigation of intracellular factors involved in methylmercury toxicity.
AB  - Methylmercury is a known pollutant that causes severe central nervous system
      disorders. It is capable of passing through the blood-brain barrier and
      accumulates in cerebral cells. However, little is known regarding the mechanism
      of its toxicity at the molecular level. Using yeast cells, we searched for the
      genes involved in the expression of methylmercury toxicity, and found that genes
      encoding L-glutamine.D-fructose-6-phosphate amidotransferase (GFAT) and ubiquitin
      transferase (Ubc3) confer methylmercury resistance on the cells. It has also been
      shown that GFAT is the target molecule of methylmercury in yeast cells. These
      findings provide important clues about the mechanism underlying methylmercury
      toxicity in mammals.

PMID- 12498318
TI  - Modification of mercury toxicity by selenium: practical importance?
AB  - The interaction between mercury and selenium may involve a variety of
      toxicologically and biochemically distinct processes. In this paper, the
      interaction between inorganic mercury and sodium selenite, the interaction most
      extensively studied, as well as the interaction between methylmercury (MeHg) and
      selenium, the interaction perhaps most significant for non-occupational human
      populations, will be discussed. It has been shown that the former interaction can
      be understood as a modification of the kinetic behavior of inorganic mercury by
      selenite, but this interaction may occur only under very limited conditions. On
      the other hand, the mechanism of the latter interaction is largely unknown, and
      kinetic modification appears to play only a minor role. An interaction between
      MeHg and seleno-proteins or a possible interaction between the inorganic mercury,
      resulting from the demethylation of MeHg, and the selenium may be important.
      Compared to the experimental findings, little evidence of the toxicological
      modification of MeHg by selenium was obtained in epidemiological studies.

PMID- 12498319
TI  - Placental to fetal transfer of mercury and fetotoxicity.
AB  - Mercury vapor is known penetrate the placental barrier more easily than inorganic
      mercury. A relative amount of mercury accumulates in the fetus after exposure of
      pregnant animals to mercury vapor. Mercury concentration in fetal organs is much
      lower than that in maternal organs except the liver, and fetal liver shows
      significantly higher mercury concentrations than maternal liver. In fetal liver,
      a substantial portion of mercury is bound to metallothionein (MT), which plays an
      important role as a reservoir of mercury during the prenatal period. The mercury
      retained in fetal liver is redistributed to other organs, such as the brain and
      kidney, with diminishing MT levels during postnatal development. Consequently, an
      increase in mercury concentration in the brain and kidney of the neonate is
      observed. In studies on animal offspring in utero exposed to mercury vapor,
      behavioral changes, such as radial arm maze, morris maze and lever-press
      durations, are observed when the levels of mercury vapor exceed the threshold
      limit value (TLV).

PMID- 12498320
TI  - Developmental neurotoxicity following prenatal exposures to methylmercury and
      PCBs in humans from epidemiological studies.
AB  - Adverse health effects following prenatal exposures to methylmercury (MeHg) have
      been apparent from several prospective cohort studies conducted in a fish-eating
      population. A prospective study in a Faroese birth cohort documented subtle
      deficits of several functional domains at prenatal MeHg exposure levels
      previously thought to be safe. Recent additional studies also showed
      neurobehavioral deficits associated with exposures to polychlorinated biphenyls
      (PCBs) with concomitant MeHg poisoning. In contrast, a prospective study in the
      Seychelles did not detect a similar association between MeHg exposure and
      neurodevelopmental deficits; children of the highest MeHg exposure group showed
      better scores in some developmental tests than those of the lower exposure groups
      for both prenatal and postnatal MeHg exposures. This paradoxical difference
      between both studies is summarized herein. The primary source of human exposure
      to MeHg is fish. Since a considerable number of pollutants, including
      polychlorinated biphenyls (PCBs) and pesticides, are also present in fish, and
      since some organochemical substances including PCBs are also well documented to
      be neurotoxic to the developing brain from epidemiological studies, the combined
      effects of these pollutants should be considered in discussing the neurotoxicity
      of MeHg. In this article, therefore, major prospective cohort studies focusing on
      the exposures to PCBs were reviewed.

PMID- 12498321
TI  - Paradigm shift in zinc: metal pathology.
AB  - Zinc (Zn) is an essential, common metal in animal tissues. Zn levels were
      elevated in only four tissues after Zn administration, the highest increase being
      in the pancreas. Zn concentration was increased by metallothionein induction.
      Metallothionein-bound Zn significantly reduced the toxicity of the metals Cd, Cu
      and Hg. It should be noted that tissue Zn levels are different in experimental
      animals and humans. Acute pancreatitis was observed following the injection of a
      large dose of Zn. Different metals have different target organs. Using metal
      pathology, treatments may be developed to save patients suffering from hepatic
      and renal diseases because Zn is used to a model animal of hepatic or renal
      disease.

PMID- 12498322
TI  - Recent studies on metallothionein: protection against toxicity of heavy metals
      and oxygen free radicals.
AB  - Metallothionein (MT) is a ubiquitous, cysteine-rich, metal-binding protein. MT
      synthesis is induced by various stimuli such as cadmium, mercury, zinc, oxidative
      stress, glucocorticoid, and anticancer agents. Recently, transgenic mice with
      loss-of-function mutations in the MT-I/-II genes were established. It has been
      assumed that MT plays a role in the detoxification of heavy metals. In recent
      studies using MT-null mice, the ability of MT to protect against cadmium-induced
      renal, liver and bone injuries has been confirmed. Moreover, MT is also capable
      of scavenging oxygen free radicals. MT is involved in the protection of tissues
      against various forms of oxidative injury, including radiation, lipid
      peroxidation, oxidative stress caused by anticancer drugs, and conditions of
      hyperoxia. However, MT still lacks an established biological function.
      Unexpectedly, the MT-null mice were apparently in good health, and the critical
      biological roles of MT have been questioned. MT seems to be a protective protein
      produced in response to a variety of stresses. Here, current studies on the
      protective roles of MT against toxicity of heavy metals and reactive oxygen
      species are reviewed, and the putative biological functions of MT are discussed.

PMID- 12498323
TI  - Perspectives on cadmium toxicity research.
AB  - Since there are a plethora of studies on cadmium toxicity and poisoning in
      laboratory animals and humans, we have limited this review to studies that are
      relevant to human health issues by focusing on carcinogenicity, genotoxicity,
      circulatory disease, nephrotoxicity and life expectancy. Cadmium exposure has
      been established to induce cancer in various tissues of laboratory animals.
      Contrary to early findings of the lack of genotoxicity by cadmium, recent
      findings of mammalian cell culture studies have revealed genotoxic effects.
      Furthermore, cadmium exposure at relatively low doses induces circulatory
      diseases in laboratory animals. Despite such results of various cadmium
      toxicities in animal studies, data from human studies are lacking and
      insufficient to support the cause-effect relationship. Although cadmium is
      currently considered to be a human carcinogen by the International Agency for
      Research and Cancer, it is inappropriate to conclude that sufficient evidence on
      the carcinogenicity of cadmium in humans exists. It is also thought that
      epidemiological studies so far reported do not support the occurrence of cadmium
      induced circulatory disease in humans. Since there are inconsistent reports on
      the relationship of cadmium exposure with the life expectancy of people living in
      cadmium-polluted areas, further studies are needed for clarification. It is also
      necessary to examine apparent discrepancies in result between humans and
      experimental animals. It has been established that long-term exposure to cadmium
      causes renal dysfunction in both humans and experimental animals, and whether
      there are any differences in the inducibility of metallothionein in the kidney
      warrants further study.

PMID- 12498324
TI  - Effects of cadmium intake on bone metabolism of mothers during pregnancy and
      lactation.
AB  - Cadmium (Cd) is a heavy metal that exists ubiquitously in the environment, and it
      interacts with essential elements such as zinc, copper, iron, and calcium (Ca).
      Particularly, Cd interferes with Ca and vitamin D metabolism in bone kidney and
      intestine. The interaction between Cd and Ca in bone, intestine, and kidney may
      result in the disorder of bone metabolism. On the other hand, pregnancy and
      lactation are also important physiological factors affecting bone metabolism in
      the mother. Ca absorption is decreased by competition with Cd in the intestine,
      and more Ca is released from maternal bone and transferred to neonate by
      lactation. In the intestine, Cd uptake competes with Ca uptake. Cd causes a
      marked decrease in bone density compared to the normal decrease in bone mineral
      density during lactation. Lactation is an important factor contributing to the
      decrease in bone mineral density and Cd has an additive effect of decreasing bone
      metabolism of mother animal, although the Cd intake level is relatively low
      (approximately 3-14 microgCd/kg/day). The relationship among maternal Cd intake,
      renal function and bone metabolism and the interaction between Cd and Ca during
      lactation are reviewed herein, together with additional data obtained recently in
      our laboratory.

PMID- 12498325
TI  - Cellular cadmium uptake mediated by the transport system for manganese.
AB  - The mechanism of cellular cadmium (Cd) uptake has been poorly understood.
      Recently, we developed Cd-resistant cell lines from metallothionein null mouse
      cells and showed that the Cd resistance of these cells was conferred primarily by
      a reduced Cd accumulation. Surprisingly, the uptake rate of manganese (Mn) was
      also markedly reduced in Cd-resistant cells. Subsequent studies on the kinetics
      of Cd and Mn uptake by Cd-resistant and parental cells revealed that the Mn
      transport system with high affinity for Mn is used for cellular Cd uptake, and
      that this pathway is suppressed in Cd-resistant metallothionein null cells. This
      is the first indication that the transport system for Mn is used for Cd uptake in
      mammalian cells. Divalent metal transporter 1 (DMT1) is the only known mammalian
      transporter involved in the uptake of both Cd and Mn. However, the high-affinity
      Mn/Cd transport system we found seems to be distinct from DMT1 because of the
      difference in optimal pH and substrate specificity. On the other hand, various
      types of Mn transporters have been shown to play an important role in cellular Cd
      uptake in non-mammalian species such as yeast, plants and bacteria, suggesting
      the existence of Mn transporters other than DMT1 in mammals.

PMID- 12498326
TI  - Retraction. A Utstein-style analysis of prognostic factors related to survival in
      out-of-hospital cardiac arrests in Akita-City, Japan.

PMID- 12498327
TI  - The consequences of different "lapses" on relapse to heroin seeking in rats.
AB  - Although human studies have shown that a lapse, the first violation of
      abstinence, often induces resumption of drug taking, or relapse, it is not known
      what aspect of a lapse is critical to relapse or whether this phenomenon can be
      studied in other species. Rats were trained to self-administer heroin accompanied
      by a discrete light stimulus. After extinction, different groups experienced
      different "lapses." Twenty-four hours later, all groups received a test for
      relapse. It was found that a lapse during which heroin was self-administered, or
      was presented in close temporal contiguity with lever pressing, induced
      subsequent heroin seeking. Simple exposure to heroin, or to heroin-related
      stimuli, during the lapse had little effect on responding in the test for
      relapse.

PMID- 12498328
TI  - How will we know a lapse when we see one? Comment on Leri and Stewart (2002).
AB  - The article by F. Leri and J. Stewart (2002) addresses the validity of animal
      models of relapse in a more sophisticated manner than does much prior research.
      These researchers have shown that drug self-administration can be influenced by
      the presence of drug contingent cues as well as by active self-administration
      versus passive infusion of "lapse" doses. This research also leads to additional
      questions about the external validity of animal relapse models. Current relapse
      models may lack validity because of the parameters of drug exposure, because
      abstinence is imposed on the organism, and because there is no motivational
      influence that counters resumption of drug self-administration. F. Leri and J.
      Stewart's (2002) article encourages a more thorough assessment of the
      motivational context of relapse models.

PMID- 12498329
TI  - On the nature of the conditioned stimulus: comment on Leri and Stewart (2002).
AB  - F. Leri and J. Stewart (2002) present convincing evidence that a relapse to
      heroin-seeking behavior is established when rats are given a momentary lapse in
      which they are allowed to respond while under the influence of heroin. Although
      exposure to a conditioned stimulus (CS) paired with heroin self-infusion did not
      induce a relapse, it was able to control responding. In addition to serving as
      both a discriminative stimulus and a conditioned reinforcer, it is argued in this
      article that the CS also may have positive hedonic value independent of its
      association with heroin and that this property should be considered in
      interpreting the results of future experiments.

PMID- 12498330
TI  - Lapses and reinstatement of heroin seeking in rats: comment on Leri and Stewart
      (2002).
AB  - In an elegant series of experiments, F. Leri and J. Stewart (2002) report that
      exposure to heroin increases subsequent reinstatement responding if the animal
      has access to the drug lever during the lapse and if responding on the lever
      results in the presentation of conditioned cues. It is interesting that exposure
      to only these conditioned cues in the absence of heroin did not affect
      reinstatement responding on the following day. Although these are important
      experiments, the results should be interpreted with some degree of caution for
      several reasons. Nevertheless, the experiments described in this article
      represent the first attempt to address the effects of self-administered versus
      investigator-delivered heroin on subsequent reinstatement behavior. Future
      research should attempt to replicate these experiments taking these
      considerations into account.

PMID- 12498331
TI  - Do animal models provide a valid analogue for human drug lapse and relapse?
      Comment on Leri and Stewart (2002).
AB  - Prior research on animal models of drug relapse has demonstrated that passive
      exposure to an addictive substance following acquisition and extinction of drug
      self-administration has a "priming effect" on subsequent drug use. The validity
      of this animal analogue of human relapse can be criticized, however, because most
      human drug relapses are precipitated by the user's voluntary self-administration
      of a substance. The results of the present study by F. Leri and J. Stewart (2002)
      clearly show that if the initial heroin lapse is self-administered by rats,
      subsequent heroin seeking during the relapse test is significantly greater than
      if the heroin is externally administered. These results help bridge the gap
      between animal and human models of drug use and highlight the significance of
      both behavioral and environmental determinants of relapse.

PMID- 12498332
TI  - The promise and pitfalls of animal and human models of relapse: comment on Leri
      and Stewart (2002).
AB  - F. Leri and J. Stewart (2002) recently presented results from an animal study of
      lapse and relapse in an attempt to model the human situation. The authors of this
      comment consider two criteria for evaluating the usefulness of animal models for
      studies of human relapse: (a) the extent to which the animal model captures the
      essential components of human lapse and relapse phenomena and (b) the extent to
      which the conceptualization guiding the animal model is congruent with modern
      research and theory on animal behavior in related preparations. The authors argue
      that F. Leri and J. Stewart's (2002) model, as of yet, does not meet the
      standards suggested by these criteria. However, features of this work may prove
      valuable for informing efforts to develop relapse paradigms in both human and
      animal research.

PMID- 12498333
TI  - Self-administration of cocaine, alfentanil, and nalbuphine under progressive
      ratio schedules: consumer demand and labor supply analyses of relative
      reinforcing effectiveness.
AB  - Progressive-ratio (PR) schedules of intravenous (i.v.) drug self-administration
      are useful for establishing the relationships between reinforcing effectiveness
      and pharmacological actions of abused drugs. The authors compared the reinforcing
      effects of the high-efficacy opioid alfentanil, the low-efficacy opioid
      nalbuphine, and cocaine using a PR schedule of i.v. drug injection in rhesus
      monkeys in which the response requirement increased during the experimental
      session and the initial response requirement (IRR) was varied. Analyses based on
      either consumer demand or labor supply models of behavioral economics revealed
      that the relative reinforcing effectiveness of cocaine and alfentanil was greater
      than that of nalbuphine. These results suggest that PR schedules with varying
      IRRs can provide meaningful estimates of the relative reinforcing effectiveness
      of abused drugs.

PMID- 12498334
TI  - Discriminative stimulus properties in rats of the novel antipsychotic quetiapine.
AB  - Rats discriminated the novel antipsychotic quetiapine (Seroquel). Full
      generalization was seen with the novel ("atypical") antipsychotics, clozapine,
      olanzapine, and risperidone. Generalization was not seen with the older "typical"
      antipsychotics, haloperidol, chlorpromazine, and loxapine, or with the novel
      atypical antipsychotic, amisulpride. The pattern of generalization resembled that
      seen in rats trained to discriminate a low dose (1.25 mg/kg) of clozapine, which
      dissociates most novel antipsychotics from typical antipsychotics. However, the
      failure of the novel antipsychotic amisulpride to generalize demonstrates that
      this bioassay does not detect all novel antipsychotics. These data suggest that
      the discrimination of antipsychotics such as quetiapine may be of value in the
      development of novel antipsychotics, although the relationship between the
      discriminative properties of such drugs and their clinical actions is unclear.

PMID- 12498335
TI  - Dantrolene diminishes forelimb force-related tremor at doses that do not decrease
      operant behavior in the rat.
AB  - A behavioral preparation that affords concurrent measurement of forelimb force
      and tremor in rats was used to assess the effects of dantrolene sodium, a muscle
      relaxant and potential neuroprotective drug. Rats that were trained to press
      downward on an isometric force transducer while simultaneously licking water
      reinforcement were administered dantrolene (5.0 mg/kg, 7.5 mg/kg, and 10.0
      mg/kg). Dantrolene diminished force output at the 7.5 mg/kg and 10.0 mg/kg doses
      and decreased tremor at all three doses. Dantrolene decreased the ratio of
      forelimb tremor to force output at all three doses. Dantrolene did not suppress
      operant behavioral output at these doses. These results suggest that dantrolene
      may affect fine motor control and decrease tremor at doses that do not produce
      behavioral suppression.

PMID- 12498336
TI  - Effects of triazolam, 8-OH-DPAT, and buspirone on repeated acquisition in
      squirrel monkeys.
AB  - The nonserotonergic benzodiazepine, triazolam, was compared with two 5-HT1A
      receptor agonists, 8-OH-DPAT and buspirone, in squirrel monkeys responding under
      a repeated-acquisition procedure. In each session, subjects acquired a 4-response
      sequence by responding sequentially on 3 keys in the presence of 4 discriminative
      stimuli (colors). Response sequences for each session were maintained by food
      presentation under a second-order fixed-ratio schedule. Errors produced a brief
      time-out but did not reset the sequence. In general, all of the drugs produced
      dose-dependent decreases in overall response rate and increases in the percentage
      of errors as the cumulative dose was increased. Together, these results indicate
      that 5-HT1A receptor agonists disrupt learning in squirrel monkeys by producing
      rate-decreasing and error-increasing effects in a manner comparable with the
      nonserotonergic benzodiazepine triazolam.

PMID- 12498337
TI  - Stimulant medication improves recognition memory in children diagnosed with
      attention-deficit/hyperactivity disorder.
AB  - The effect of stimulant medication on recognition memory was examined in 18
      children with attention-deficit/hyperactivity disorder (ADHD). Recognition memory
      was assessed using a delayed matching-to-sample task at 6 delays ranging from 1
      to 32 s. Each child was tested on 2 separate occasions, once 60 to 90 min after
      taking stimulant medication and the other at least 18 hr after taking medication.
      Children performed significantly better on medication than off. Stimulant
      administration significantly increased accuracy and the number of nickel
      reinforcers earned. Decreases in observing response latency and correct choice
      response latency occurred after taking stimulant medication. The results indicate
      that stimulant medication improved recognition memory for children with ADHD.

PMID- 12498338
TI  - Kinetic assessment of the effects of task difficulty, microencephaly, and a
      response manipulandum alteration on the rate of fixed-ratio discrimination
      acquisition.
AB  - Fixed-ratio discrimination (FRD) training session-accuracy curves were
      constructed using first-order, nonlinear regression and probit analyses to
      determine maximal (asymptotic) accuracy and the number of sessions required to
      reach half-maximal accuracy. Increased FRD difficulty (reductions in the
      differences between the 2 fixed-ratio values to be discriminated) and a training
      parameter change each increased the number of sessions required to reach half
      maximal accuracy and decreased maximal FRD accuracy (i.e., session-accuracy
      curves were shifted down and to the right) regardless of analysis procedure.
      These findings indicate that the above manipulations induced mixed competitive
      noncompetitive inhibition of the rate of FRD learning. Microencephalic rats were
      more sensitive to increases in FRD difficulty, whereas control rats were more
      sensitive to the training parameter change.

PMID- 12498339
TI  - Constraints on information processing under alcohol in the context of response
      execution and response suppression.
AB  - This study tested the degree that alcohol restricts information processing on
      tasks requiring response execution and response suppression. A dual task required
      12 participants to respond to 2 task stimuli (Tasks 1 and 2) presented in close
      succession. The task was performed before and after receiving 3 alcohol doses
      (placebo, 0.45 g/kg, and 0.65 g/kg) administered on separate days in a
      counterbalanced order. Alcohol increased task interference, as evidenced by
      increased time to respond to Task 2. Impairment was comparable regardless of
      whether Task 1 required a response to be executed or suppressed. The evidence
      supports a resource limitation account that argues that alcohol reduces capacity
      to process information required for execution and suppression of responses.

PMID- 12498340
TI  - The relations among personality, symptoms of alcohol and marijuana abuse, and
      symptoms of comorbid psychopathology: results from a community sample.
AB  - This study examined the relation of the Five-Factor Model (FFM) of personality to
      symptoms of alcohol and marijuana abuse before and after controlling for symptoms
      of antisocial personality disorder (APD) and internalizing psychopathology. The
      481 participants completed a well-validated measure of the FFM and a structured
      diagnostic interview at age 21 years. Hierarchical regression analyses indicated
      that unique constellations of personality characteristics were associated with
      symptoms of alcohol abuse, marijuana abuse, APD, and internalizing disorders. For
      example, symptoms of alcohol abuse were associated with high Extraversion and low
      Conscientiousness, whereas symptoms of marijuana abuse were characterized by low
      Extraversion and high Openness to Experience. Findings have implications for
      models of the etiology and treatment of substance use and abuse.

PMID- 12498341
TI  - EEG coherence following acute and chronic clozapine in treatment-resistant
      schizophrenics.
AB  - Electroencephalographic (EEG) coherence is an index of brain regional coupling
      that has been found to be abnormal in people with schizophrenia but has not been
      systematically examined in response to neuroleptics. EEG coherence in slow (delta
      and theta) frequencies was assessed in 17 treatment-resistant people with
      schizophrenia at baseline, 2 hr after their first oral dose (25 mg) and after 6
      weeks of clozapine treatment. Compared with EEG norms, participants exhibited
      significant interhemispheric and intrahemispheric coherence abnormalities prior
      to treatment. Both acute and chronic treatments altered coherence but differed
      with respect to their relationship to symptom reduction and their ability to
      normalize or augment pretreatment abnormalities. Findings are discussed in
      relation to "disconnection" theories of schizophrenia.

PMID- 12498342
TI  - Interstitial telomeric sites and NORs in Hartmann's zebra (Equus zebra
      hartmannae) chromosomes.
AB  - Interstitial telomeric sites (ITSs) are considered as signatures of chromosomal
      rearrangements that take place during karyotype evolution. Understanding that
      equids have undergone rapid karyotype evolution compared with the average in
      other mammals, a search of these signatures was carried out in the Hartmann's
      mountain zebra (Equus zebra hartmannae; EZH) chromosomes. Six consistent ITSs
      were identified on five of the zebra chromosomes (EZH1p, 1q, 2q, 5q, 6q and 11q).
      The location of these ITSs coincided with fusion points of some of the
      evolutionarily conserved human-Hartmann's zebra chromosomal segments suggesting
      that the sequences are remnants of fusion events between ancestral chromosomes.
      Incidentally, three of the ITSs also matched with the presence of constitutive
      heterochromatin. Further, ribosomal gene clusters were localized on five zebra
      chromosomes and the data were compared with those in other equid species. The
      findings offer preliminary evidence on the likely evolution of some of the
      Hartmann's zebra chromosomes and add to the current search for clues that lead to
      the ancestral chromosomal configuration in equids.

PMID- 12498343
TI  - The 3D structure of human chromosomes in cell nuclei.
AB  - The spatial arrangement of some genetic elements relative to chromosome
      territories and in parallel with the cell nucleus was investigated in human
      lymphocytes. The structure of the chromosome territories was studied in
      chromosomes containing regions (clusters) of highly expressed genes (HSA 9, 17)
      and those without such clusters (HSA 8, 13). In chromosomes containing highly
      expressed regions, the elements pertaining to these regions were found close to
      the centre of the nucleus on the inner sides of chromosome territories; those
      pertaining to regions with low expression were localized close to the nuclear
      membrane on the opposite sides of the territories. In chromosomes with generally
      low expression (HSA 8, 13), the elements investigated were found symmetrically
      distributed over the territories. Based on the investigations of the chromosome
      structure, the following conclusions are suggested: (1) Chromosome territories
      have a non-random internal 3D structure with defined average mutual positions
      between elements. For example, RARalpha, TP53 and Iso-q of HSA 17 are nearer to
      each other than they are to the HSA 17 centromere. (2) The structure of a
      chromosome territory reflects the number and chromosome location of clusters of
      highly expressed genes. (3) Chromosome territories behave to some extent as solid
      bodies: if the territory is found closer to the nuclear centre, the individual
      genetic elements of this chromosome are also found, on average, closer the centre
      of the nucleus. (4) The positions of centromeres are, on average, nearer to the
      fluorescence weight centre of the territory (FWCT) than to genes. (5) Active
      genes are not found near the centromeres of their own territory. A simple model
      of the structure of chromosome territory is proposed.

PMID- 12498344
TI  - Differential association of SMC1alpha and SMC3 proteins with meiotic chromosomes
      in wild-type and SPO11-deficient male mice.
AB  - SMC proteins are components of cohesin complexes that function in chromosome
      cohesion. We determined that SMC1alpha and SMC3 localized to wild-type mouse
      meiotic chromosomes, but with distinct differences in their patterns. Anti-SMC3
      coincided with axial elements of the synaptonemal complex, while SMC1alpha was
      observed mainly in regions where homologues were synapsed. This pattern was
      especially visible in pachytene sex vesicles where SMC1alpha localized only
      weakly to the asynapsed regions. At diplotene, SMC3, but not SMC1alpha, remained
      bound along axial elements of desynapsed chromosomes. SMC1alpha and SMC3 were
      also found to localize along meiotic chromosome cores of Spo11 null
      spermatocytes, in which double-strand break formation required for DNA
      recombination and homologous pairing were disrupted. In Spo11 -/- cells,
      SMC1alpha localization differed from SMC3 again, confirming that SMC1alpha is
      mainly associated with homologous or non-homologous synapsed regions, whereas
      SMC3 localized throughout the chromosomes. Our results suggest that the two
      cohesin proteins may not always be associated in a dimer and may function as
      separate complexes in mammalian meiosis, with SMC1alpha playing a more specific
      role in synapsis. In addition, our results indicate that cohesin cores can form
      independently of double-strand break formation and homologous pairing.

PMID- 12498345
TI  - Transient CENP-E-like kinetochore proteins in plants.
AB  - Derived from candidate sequences of a barley EST database two proteins with
      homology to the coiled coil region of the human kinetochore protein (KP) CENP-E
      were generated and classified as centromere protein E-like 1 and 2 (Cpell and
      Cpe12). Specific antibodies produced against recombinant Cpe11 and Cpe12 proteins
      labeled the centromere on mitotic chromosomes of barley and field bean and
      recognized specifically proteins from nuclear/chromosomal protein extracts on
      immunoblots. No function was predicted for homologues of Cpe11 within the
      databases for Arabidopsis and rice genomes. However, the centromeric location of
      Cpe11 and Cpe12 suggests they may have a function within the kinetochore. Plant
      homologues to barley Cpe12 are N-type kinesins, suggesting that Cpe12 is
      functionally homologous to human CENP-E.

PMID- 12498346
TI  - The use of laser microdissection for the preparation of chromosome-specific
      painting probes in farm animals.
AB  - Laser microbeam microdissection and laser pressure catapulting procedure were
      used for the construction of chromosome-specific painting probes, arm-specific
      probes and probes for chromosomal subfragments. We report on a method for
      generation of fluorescence in-situ hybridization probes from laser dissected
      chromosomes of farm animals. So far, using the described method, a set of
      chromosome-specific painting probes has been obtained for all porcine
      chromosomes, 17 chromosomes of cattle and selected equine chromosomes. It is
      concluded that the laser technology appears to be a useful and powerful tool for
      the construction of chromosome-specifi c painting probes. Its main advantage is
      the fast non-contact collection of chromosomes.

PMID- 12498347
TI  - Allele-specific underacetylation of histone H4 downstream from promoters is
      associated with X-inactivation in human cells.
AB  - We have used a novel approach to investigate the histone H4 acetylation status at
      X-inactivated genes compared with their active counterparts. Immunoprecipitation
      with a sheep antibody that preferentially binds multiply-acetylated H4 isoforms
      was used to select hyperacetylated chromatin from a human female lymphoblastoid
      cell line exhibiting non-random X-inactivation as a result of an X/autosome
      translocation. The distribution of active and inactive gene sequences between the
      immunoprecipitated and bulk chromatin was compared at four X-linked loci
      containing intragenic polymorphic microsatellite repeats to allow identification
      of individual alleles by polymerase chain reaction. We find that DNA sequences
      corresponding to transcriptionally silent alleles are consistently under
      represented in the hyperacetylated fraction. As the microsatellite repeat
      sequences used to identify alleles range in distance from 6.5 kb to 25 kb
      downstream of promoters, we conclude that differential H4 acetylation of active
      and silent chromatin is not confined to regions involved in the initiation of
      transcription, contrary to previous reports.

PMID- 12498348
TI  - Higher-order organization and compartmentalization of satellite DNA PIM357 in
      species of the coleopteran genus Pimelia.
AB  - The PIM357 satellite DNA family is present in 26 Pimelia taxa (Tenebrionidae,
      Coleoptera) with endemic congeneric species from the Canary Islands showing
      higher interrepeat variability than continental ones. In this paper, we compare
      the repetitive DNA sequences of a Canarian species that has distinct subfamilies
      of repeat units, P. radula ascendens, with another without such subfamilies, P.
      sparsa sparsa. The chromosomal localization of the repeat units and the
      comparison of the variability of randomly cloned monomers to the one estimated by
      comparing repeat units from dimers and trimers suggest the absence of satellite
      subfamilies in P. sparsa sparsa. Hence, the repeat units of this species seem to
      be uniformly and randomly distributed throughout all chromosomes out of one
      chromosomal pair. On the contrary, P. radula ascendens shows four divergent
      subfamilies of repeat units supported by several diagnostic nucleotide
      substitutions. These subfamilies seem to form four distinct repeat units: monomer
      subfamily 1, monomer subfamily 4 and two higher-order units (dimer linking
      subfamily 1 and 4, and dimer linking subfamily 2 and 3). Moreover, monomers of
      subfamily 1 are present in three chromosomal pairs only. We discuss the effect of
      different potential factors acting in the concerted evolution and the genomic
      organization of stDNA sequences in these taxa.

PMID- 12498349
TI  - Genetic load caused by variation in the amount of rDNA in a wasp.
AB  - Extensive variation in the size of the short (heterochromatic) arm of chromosome
      14 was found in the wasp Trypoxylon (Trypargilum) albitarse. Ten different
      variants were differentiated by size and C-banding pattern. Fluorescent in-situ
      hybridization (FISH) revealed that ribosomal DNA in this species is clustered in
      the darkly C-banded parts of the heterochromatic short arm of chromosome 14. On
      this basis, we got an indirect estimate of the amount of rDNA from the area of
      these dark C-bands. The significant absence in males of the three chromosome
      variants with lower amounts of rDNA indicates that these three variants are
      lethal in this sex, and suggests the existence of a threshold marking the minimum
      amount of rDNA which is tolerable in haploidy. This implies about 4% genetic load
      in the population caused by variation in rDNA amount.

PMID- 12498350
TI  - A comparison of the occurrence and nature of vocal symptoms in two groups of
      Icelandic teachers.
AB  - Research suggests that teaching activities involve a high risk of developing
      voice disorders. The aim of this study is to examine the possible difference in
      the occurrence and nature of vocal symptoms in two groups of teachers-head
      teachers (N = 43), including both principals and assistant head teachers, and
      teachers of physical education (N = 43)--and to investigate the possible role of
      gender. The questionnaire results indicate that demands on the voice for P.E.
      teachers and head teachers are different. The findings suggest that (i) demands
      influence the occurrence and nature of reported vocal symptoms, (ii) that
      teachers of physical education are at a greater risk of developing voice
      problems, and (iii) that female P.E. teachers are at particular risk.

PMID- 12498351
TI  - Some objective measures indicative of perceived voice robustness in student
      teachers.
AB  - One of the problems confronted in the teaching profession is the maintenance of a
      healthy voice. This basic pedagogical tool is subjected to extensive use, and
      frequently suffers from overload, with some teachers having to give up their
      profession altogether. In some teacher training schools, it is the current
      practice to examine the student's voice, and to refer any perceived
      susceptibility to strain to voice specialists. For this study, a group of vocally
      healthy students were examined first at the teacher training schools, and then at
      the ENT clinic at the University Hospital of Nijmegen. The aim was to predict
      whether the subject's voice might be at risk for occupational dysphonia as a
      result of the vocal load of the teaching profession. We tried to find objective
      measures of voice quality in student teachers, used in current clinical practice,
      which reflect the judgements of the therapists and phoniatricians. We tried to
      explain such measures physiologically in terms of robustness of, and control over
      voicing. Objective measures used included video-laryngostroboscopy, phonetography
      and spectrography. Maximum phonation time, melodic range in conjunction with
      maximum intensity range, and the production of soft voice are suggested as
      possible predictive parameters for the risk of occupational voice strain.

PMID- 12498352
TI  - Changes in voice during a day in normal voices without vocal loading.
AB  - Various changes in vocal parameters have been observed during the working days of
      voice professionals, e.g. teachers. The present study investigated vocal
      parameters during daytime when voice was not used. Eleven females and ten males
      (mean ages 30 and 40 years) volunteered as subjects. They recorded the same
      reading task in the forenoon and in the afternoon with an interval of 6-8 hours.
      Between the recordings voice use was avoided. Six females repeated the test in
      six days with the intervals from one week to three months. Fundamental frequency
      (F0) and sound pressure level (SPL) were measured. Voice quality was studied by
      calculating the alpha ratio (SPL 1000-5000 Hz/SPL 50-1000 Hz). In most cases F0
      was higher in the afternoon, although the change was on the average small (in
      most cases within 5 Hz) and statistically non-significant. Alpha ratio was
      significantly higher for the females and lower for the males in the afternoon.
      Similar changes have been reported after vocal loading. The results suggest that
      studies on the effects of vocal loading should also address changes in vocal
      parameters when no vocal loading is present. Gender difference in the vocal
      changes warrants further study.

PMID- 12498353
TI  - Comparisons between therapists' and patients' views of dysphonia: a survey study.
AB  - Speech and language therapists (SLTs) recognise the need to involve patients in
      the design and implementation of services. The present study describes the
      results of a questionnaire survey undertaken among SLTs working with patients
      with voice disorders to determine whether patients' and therapists' views on
      issues around dysphonia were in harmony. The SLTs' views of patients'
      disabilities and handicaps associated with dysphonia are reported and compared
      with those of an earlier survey of patient-reported difficulties (Scott et al.
      Clin Otolaryngol 1997; 22: 37-40). A close, but incomplete, match of therapists'
      and patients' views of dysphonia is reported and discussed.

PMID- 12498354
TI  - Stability of memory traces for speech sounds in cochlear implant patients.
AB  - For this study, we examined the perception and production of vowels by
      postlingually deafened patients with cochlear implant. Four patients and one
      normally hearing subject produced typical vowel sounds of Finnish by using a
      speech synthesizer. Also acoustic analyses of the pronounced vowels were made.
      The first (F1) and the second (F2) formant frequencies were measured. The
      mismatch negativity (MMN), a cortical cognitive auditory event related potential,
      was used to measure objectively the patients' preattentive discrimination of a
      prototypical /i/ sound from deviants differing in the F2 continuum. In the
      phonetic tests the hyperspace effect was seen also among the patients. The MMN,
      which reflects the phonetic discrimination ability, could be identified from the
      patient with the best vowel perception abilities. The phonetic memory traces once
      developed for vowels seem to remain quite stable even though they have not been
      activated by vowel information for years.

PMID- 12498355
TI  - Personality and close relationships: embedding people in important social
      contexts.
AB  - This special issue of the Journal of Personality is predicated on the assumption
      that close relationships provide the central stage for the drama of human
      experience. This all-important context both shapes and conditions the expression
      of personality, and thus must play an integral role in any truly adequate account
      of human behavior. The importance of this agenda is perhaps overshadowed only by
      its difficulty. Contributions to the present issue, therefore, take stock of past
      research, highlight current state-of-the-art research, and offer a vision of the
      next generation of research on personality and close relationships. The
      conceptual and methodological approaches highlighted in this issue remain
      faithful to the dynamic, interdependent, and multilayered nature of the processes
      linking personality and close relationships.

PMID- 12498356
TI  - Seventy years of research on personality and close relationships: substantive and
      methodological trends over time.
AB  - The present review is based on a quantitative analysis of the abstracts for 477
      studies published since 1932 on the topic of personality and close (romantic)
      relationships. This approach enables a "bird's-eye" view of the content and
      methods that have characterized research in this area and an examination of
      publication trends over time. Results showed that 60% of all published studies in
      this area relied exclusively on cross-sectional and self-report methods; that
      nearly all used convenience samples, though more than half used nonstudent
      samples; and that more than one-third relied exclusively on data from individuals
      rather than couples. Few studies appeared to include elaborated networks of
      constructs in either the personality or relationship domain or to attempt to
      integrate an elaborated model of personality with an elaborated relationship
      model. Examination of trends over time revealed a mixed picture, with increasing
      use of the least informative designs balanced by evidence of increasingly complex
      conceptual models.

PMID- 12498357
TI  - Finding the person in personal relationships.
AB  - The search for dispositional factors that influence the course and conduct of
      close relationships has long and popular roots. No cogent theory of interpersonal
      processes would deny that dispositional factors matter, and, furthermore, both
      scholarly and lay analyses often emphasize them. Although existing research has
      made progress in understanding how dispositions affect behavior in ongoing
      relationships, when all is said and done, this progress has been modest. In this
      paper, we discuss several interlocking theoretical and methodological principles
      that may facilitate movement to the next (and more sophisticated) generation of
      theory and research. We draw particularly on interdependence theory to discuss
      the concepts of relationship and persons-in-relationship. Central to our analysis
      is the principle that interaction in relationships is an inherently dynamic,
      temporal, and thoroughly interdependent process that cannot be properly
      understood from examination of the static, global dispositions of one of its
      members. To provide grounding for our analysis, we also discuss several specific
      implications of these concepts for the conduct of research seeking to understand
      personality in relationships.

PMID- 12498358
TI  - Personality in context: an interpersonal systems perspective.
AB  - Because a significant part of individuals' lives involve close relationships, an
      important and substantial part of the situations they encounter consists of other
      people's behaviors. We suggest that individuals' characteristic ways of behaving,
      which are typically attributed to "personality," arise from two processes. One
      lies primarily within the individual, conceptualized as individual differences in
      one's cognitive and affective processing system. The other process, which has
      received less attention in personality research, lies outside the person in the
      individual differences in the situations that people encounter in their everyday
      lives. The interplay between these two processes can be particularly relevant for
      understanding close relationships. By assuming that each partner's behavior
      provides the situational context for the other partner, we conceptualize a dyadic
      relationship as the "interlocking" of the cognitive-affective processing systems
      of both partners. We illustrate this approach to personality-in-context with a
      hypothetical scenario and use this framework to organize research on attachment
      styles, rejection sensitivity, self-fulfilling prophecy, the self in relation to
      others, and interdependence theory.

PMID- 12498359
TI  - Modeling the personality of dyads and groups.
AB  - The paper presents a methodological approach for assessing the personality of a
      dyad or a group, a concept that is not equivalent to the sum, or mean, of the
      individual scores. We illustrate how the logic of the multitrait multimethod
      approach, which is a familiar technique for establishing construct validity, can
      be extended to assess the construct of a relationship "personality." The model,
      which we call the latent group model, provides a decomposition and comparison of
      individual-level and group-level variance in a given trait, and the individual
      level and group-level covariance or correlation between two traits. The model is
      also extended to the assessment of stability of the individual and group level
      traits. Throughout the paper, we draw connections between related methods and
      show how the latent group model can be estimated through hierarchical linear
      modeling.

PMID- 12498360
TI  - It's not just who you're with, it's who you are: personality and relationship
      experiences across multiple relationships.
AB  - The present study examined the influence of stable personality traits on romantic
      relationships using longitudinal data on a large, representative sample of young
      adults. Relationship experiences (quality, conflict, and abuse) showed relatively
      small mean-level changes over time and significant levels of rank-order
      stability, even across different relationship partners. Antecedent personality
      traits (assessed at age 18) predicted relationship experiences at age 26 and
      change in relationship experiences from age 21 to 26. Conversely, relationship
      experiences also predicted change in personality. Importantly, these findings
      generally held across relationship partners, suggesting that some people tend to
      be generally happy (or unhappy) across relationships, and this is due, in part,
      to stable individual differences in personality. Discussion focuses on the
      broader implications of the findings, in particular the need for relationship
      researchers to consider the importance of personality for why relationships
      thrive or fail and the need for personality researchers to consider the impact of
      relationship experiences on intraindividual personality development.

PMID- 12498361
TI  - Psychosocial vulnerability from adolescence to adulthood: a prospective study of
      attachment style differences in relationship functioning and partner choice.
AB  - Using a prospective research design, this study explored whether attachment style
      during adolescence forecasts the nature and quality of romantic relationships in
      early adulthood and investigated two general pathways for explaining these
      effects. Black and White community residents were first interviewed in
      adolescence at which time they completed a self-report measure of attachment
      style. Approximately 6 years later, they participated in a follow-up interview
      along with their current romantic partners (N = 224 couples). Results revealed
      that insecure attachment in adolescence was a risk factor for adverse
      relationship outcomes in adulthood, although the effects were most consistent for
      avoidant attachment. Avoidant adolescents were involved in relationships that
      they (and their partners) rated as less satisfying overall; they also engaged in
      fewer pro-relationship behaviors, and perceived that their partners engaged in
      fewer pro-relationship behaviors. In addition, avoidant adolescents were involved
      with partners who had less healthy personality profiles. Results for anxious
      ambivalent and secure attachment were weaker, more complex, and moderated by
      gender. This study provides the first prospective evidence that avoidant
      attachment places individuals at risk for adverse relationship outcomes and
      highlights potential pathways through which this occurs.

PMID- 12498362
TI  - Self-respect and pro-relationship behavior in marital relationships.
AB  - This work advances an interdependence theoretic analysis of the role of self
      respect in ongoing close relationships. Self-respect is defined as the tendency
      to perceive the self as a principled person who is worthy of honor and high
      regard and is argued to rest on moral integrity. Consistent with predictions,
      results from a study of marital relationships revealed that individual self
      respect is positively associated with both the individual's and the partner's pro
      relationship behavior (accommodation, forgiveness, conciliation). Mediation
      analyses revealed that self-respect not only exhibits direct associations with
      each person's behavior, but also exhibits indirect associations with each
      person's behavior, via the impact of each person's actions on reciprocal pro
      relationship behavior from the partner. Mediation was more reliably observed for
      the association of self-respect with partner behavior than for the association
      with individual behavior. Both individual pro-relationship behavior and partner
      pro-relationship behavior are positively associated with couple well-being, which
      in turn is positively associated with personal well-being (life satisfaction,
      physical health, psychological adjustment). These associations were evident in
      both within-participant and across-partner analyses and for both self-report and
      interaction-based measures of behavior. Self-respect reliably accounts for unique
      variance beyond variance attributable to self-esteem.

PMID- 12498363
TI  - Witnessing interparental psychological aggression in childhood: implications for
      daily conflict in adult intimate relationships.
AB  - We examined the consequences of witnessing interparental psychological aggression
      in childhood for daily conflict processes in adult intimate relationships. Both
      partners in 73 heterosexual couples provided daily diary reports of relationship
      conflict over a 28-day period. Partners' reports of witnessing mother-to-father
      and father-to-mother psychological aggression were used to predict exposure to
      daily relationship conflicts and reactivity to those conflicts (as reflected in
      end-of-day anger). Results showed no evidence of exposure effects: Witnessing
      interparental psychological aggression was unrelated to the number of conflict
      days reported by either partner. Reactivity effects emerged for males only, with
      father's aggression predicting increased reactivity and mother's aggression
      predicting the opposite. However, we found evidence of direct or unmediated
      effects of interparental conflict on daily anger for both males and females.
      Mirroring the reactivity pattern, the same-sex parent's psychological aggression
      predicted greater daily anger, whereas the opposite-sex parent's aggression
      predicted less daily anger. These effects emerged independently of Big Five
      measures of personality; moreover, Big Five measures did not predict outcomes
      independently of interparental aggression.

PMID- 12498364
TI  - Judgments of a relationship partner: specific accuracy but global enhancement.
AB  - How do partners in satisfying close relationships perceive each other? Some argue
      that relationships benefit from each partner having an accurate view of the
      other, while others maintain that partners benefit when they perceive each other
      in the most positive light possible. The current paper proposes that each of
      these benefits operates at a separate level of abstraction. Specifically, we
      propose that satisfied partners tend to be accurate in their specific perceptions
      of each other, but enhancing in their global evaluations. To address hypotheses
      derived from this model, global and specific perceptions of self and partner were
      obtained from a sample of 82 newlywed couples. Results indicate that: 1) trait
      perceptions assessed by different commonly used measures differ significantly in
      their breadth; 2) broader or more global traits are rated as significantly more
      desirable and important; 3) spouses in satisfying marriages describe their
      partners' positive traits in more global terms and their negative traits in more
      specific terms; and 4) spouses perceive each other more accurately on specific
      traits than global traits.

PMID- 12498365
TI  - Analysis of spiral ganglion cell populations in children with normal and
      pathological ears.
AB  - This study analyzed features of total and segmental spiral ganglion cell
      populations in children with normal ears and those with various pathological
      conditions. Sixty-three human temporal bone specimens, obtained from 43 children
      4 days to 9 years of age, were studied histopathologically. These specimens were
      divided into 5 diagnostic groups: group 1, normal ears (13 ears); group 2,
      congenital infectious diseases (13 ears); group 3, chromosomal aberrations (11
      ears); group 4, multiple craniofacial anomalies with hereditary or genetic causes
      (21 ears); and group 5, perinatal and postnatal asphyxia (5 ears). Eighteen of
      the 63 ears had documented profound deafness. In either normal ears (group 1) or
      those with various pathological conditions (groups 2 through 5), the total number
      of ganglion cells did not change as a function of age during the first 10 years.
      The total number of ganglion cells was significantly larger in group 1 (33,702)
      than in each of groups 2, 3, 4, and 5 (p < .01), and the number was significantly
      larger in group 2 than in each of groups 4 and 5 (p < .01 and p < .05,
      respectively). The ratio of basal to apical ganglion cell populations remained
      constant in both normal and pathological ears. Each ratio of the number of basal
      and apical ganglion cells in groups 2, 3, 4, and 5 to the mean number in group 1
      (basal and apical survival ratios) was at least approximately 40%. There was no
      statistical difference between these two ratios in groups 2, 3, 4, and 5. The
      mean (+/-SD) total number of ganglion cells in ears with documented profound
      deafness was 15,417 +/- 5,944, which is approximately 40% of those present in
      normal ears. Our results suggest that normally, cochlear neurons are completely
      present at birth and minimally regress during the first decade of life. In
      addition, although intergroup differences among various pathological groups were
      present, the majority of pathological ears had more than 10,000 spiral ganglion
      cells present. Cochlear implantation has gradually been recognized as an
      effective and reliable tool for rehabilitation of children who have profound
      deafness, even congenitally or prelingually deafened children. On the basis of
      the results obtained in this study, we discuss the implications for cochlear
      implantation in children.

PMID- 12498366
TI  - New treatment options for lymphangioma in infants and children.
AB  - Lymphangiomas are congenital malformations of the lymphatic system. These lesions
      occur most often in the head and neck area, and their treatment continues to be a
      challenge. Fortunately, a number of advances have occurred in the diagnosis and
      management of lymphatic malformations in the past decade. The purpose of this
      article is to clarify the embryology, pathogenesis, histopathology, and
      classification of these lesions, as well as to describe their various forms of
      clinical presentation. We provide a complete review of the diagnostic measures
      available and thoroughly discuss new therapeutic interventions proposed to treat
      lymphangiomas.

PMID- 12498367
TI  - Repair of a type IV laryngotracheoesophageal cleft with cardiopulmonary bypass.
AB  - Laryngotracheoesophageal clefts (LTECs) are rare congenital defects of variable
      severity depending on the extent of malformation. Management of a complete LTEC
      represents a major surgical and anesthetic challenge. The main problems are
      achieving adequate operative exposure and maintaining ventilatory support during
      and after the operation. We describe correction of a type IV LTEC extending down
      to the carina in an infant who had respiratory distress at birth. Surgical repair
      was achieved in a single stage by an anterior sternotomy approach on the 11th day
      of life. The procedure was facilitated by cardiopulmonary bypass. After the
      operation, the infant was intubated, mechanically ventilated, and sedated. Nissen
      fundoplication and gastrostomy were carried out on the 11th postoperative day.
      The child was extubated on the 12th postoperative day. The rationale for this
      method and its advantages in comparison with other surgical approaches are
      discussed.

PMID- 12498368
TI  - Nasal polyposis in children with cystic fibrosis: a long-term follow-up study.
AB  - The incidence of nasal polyposis among children 5 to 18 years of age with cystic
      fibrosis (CF) was investigated with a systematic examination of all children on
      the local CF register. Out of 23 children with CF, 13 had endoscopic evidence of
      nasal polyposis. Four children had grade 2 polyposis, and 9 children had grade 3
      polyposis. Complete opacity of the maxillary sinus was identified on a computed
      tomographic sinus scan in all but 2 of the children. Only 1 child had a developed
      frontal sinus. Between 1989 and 2000, 12 children underwent radical endoscopic
      sinus surgery for their nasal polyposis. There was good postoperative improvement
      in all of the children; however, 7 eventually required revision surgery because
      of recurrence of the nasal polyps. The median interval between repeated sinus
      surgeries was 4 years (range, 18 months to more than 6 years). This information
      can help in the counseling of parents when sinus surgery is considered for
      children with CF.

PMID- 12498369
TI  - Paraganglioma of the cervical sympathetic trunk.
AB  - We report the case of a 17-year-old man who presented with left-sided Horner's
      syndrome. Magnetic resonance imaging revealed a spindle-shaped cervical tumor in
      the left paravertebral space. During operation, a tumor originating from the left
      sympathetic trunk was found. The histopathologic analysis showed a sympathetic
      paraganglioma. The sympathetic trunk is an extremely rare location for a cervical
      paraganglioma; only a few cases have been reported in the literature.

PMID- 12498370
TI  - Effects of nimodipine on salicylate ototoxicity.
AB  - The purpose of this study was to examine the effects of nimodipine on salicylate
      ototoxicity in guinea pigs. The compound action potential (CAP) was recorded at
      the round window, and the cochlear blood flow (CBF) was measured simultaneously
      from the lateral wall of the basal turn of the cochlea by laser Doppler
      flowmetry. After administration of salicylate (100 mg/kg), the CAP thresholds
      were significantly elevated, by 5 to 20 dB (p < .05), and the CBF was
      significantly decreased (p < .05). After administration of nimodipine (2 mg/kg),
      the CAP thresholds were unchanged, but the CBF had increased significantly (p <
      .05), while systemic blood pressure had decreased significantly (p < .05).
      Simultaneous administration of both salicylate (100 mg/kg) and nimodipine (2
      mg/kg) resulted in significant elevation of the CAP thresholds (p < .05), while
      the CBF did not decrease. These results suggest that nimodipine prevents the
      decrease in CBF induced by salicylate, but that nimodipine does not prevent the
      deterioration in the CAP.

PMID- 12498371
TI  - Glucocorticoid-induced differential expression of the sialylated and
      nonsialylated Lewis(a) epitopes and respective binding sites in human nasal
      polyps maintained under ex vivo tissue culture conditions.
AB  - We characterized the anti-inflammatory effects of budesonide on the expression of
      adhesion molecules involving Lewis(a) (Le(a)) epitope, its sialylated derivative
      (sLe(a)), and their respective binding sites in human nasal polyposis. By
      computer-assisted microscopy, we quantitatively characterized the level of
      histochemical expression of L- and P-selectins, sialylated and nonsialylated
      Le(a) epitopes, and their respective binding sites in both surface epithelium and
      glandular epithelium of human nasal polyps obtained from surgical resection,
      maintained under ex vivo tissue culture conditions for 24 hours, and treated or
      not with budesonide. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell
      adhesion molecule 1 (VCAM-1) were chosen as methodological controls, because data
      already published in the literature clearly indicated budesonide-mediated effects
      on ICAM-1 and VCAM-1 levels of expression. The present data show that budesonide
      significantly modified the levels of expression of ICAM-1 and VCAM-1, and to a
      lesser extent that of P-selectin, in the surface and glandular epithelia.
      Budesonide markedly decreased the levels of expression of the binding sites for
      both Le(a) and sLe(a), while those of Le(a) and sLe(a) remained globally
      unchanged. In conclusion, the present study documents that glucocorticoid-induced
      effects can encompass receptors for Le(a) epitopes different from E- and P
      selectins on epithelial cells of human nasal polyps.

PMID- 12498372
TI  - Hearing loss in Usher syndrome type II is nonprogressive.
AB  - Usher syndrome is an autosomal recessive disorder characterized by sensorineural
      hearing loss and progressive visual loss secondary to retinitis pigmentosa. In
      the literature, a possible progression of the moderate to severe hearing loss in
      Usher syndrome type II (Usher II) is controversial. We studied the development of
      the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type
      II intraindividually and interindividually by repeatedly performing complete
      audiological and neuro-otologic examinations. Our data show a very characteristic
      slope of the hearing curve in all Usher II patients and no clinically relevant
      progression of the hearing loss over up to 17 years. The subjective impression of
      a deterioration of the communicative abilities of Usher II patients must
      therefore be attributed to the progressive visual loss. The patients should be
      reassured that changes in their hearing abilities are unlikely and should be
      provided with optimally fitted modern hearing aids.

PMID- 12498373
TI  - Osteocartilaginous differentiation of mucosal melanoma in the sinonasal cavity.
AB  - We present a very rare case of mucosal melanoma with osteocartilaginous
      differentiation (MMOD). This is the first report of MMOD originating in the
      sinonasal cavity. Preoperative diagnosis of this tumor from specimens resected
      for biopsy alone is very difficult, because it has 2 histopathologic components:
      a primary melanoma site and the part of the melanoma with osteocartilaginous
      differentiation. The immunohistochemical technique is useful in histopathologic
      diagnosis of this tumor. Malignant melanoma usually shows reactivity with MelanA
      (melanoma tumor antigen) and S-100 proteins. We diagnosed this case as MMOD
      because both regions in this tumor were stained with MelanA and S-100 proteins.
      Magnetic resonance imaging provides the best clinical ability to detect malignant
      melanoma in the sinonasal region. In this case, the melanotic melanoma site in
      the posterior ethmoid sinus appeared hyperintense to gray matter on T1-weighted
      image magnetic resonance imaging. Thus, it would have been possible to diagnose
      this case as MMOD before operation, even though we could not obtain a biopsy
      specimen from the posterior ethmoid sinus lesion.

PMID- 12498374
TI  - Hyperviscoelasticity of epipharyngeal mucus may induce globus pharyngis.
AB  - Detailed observation reveals a lump of translucent sticky mucus standing in the
      epipharynx of most globus patients, suggesting that the mucus adherent to the
      epipharynx causes a globus sensation. The epipharyngeal mucus of 70 consecutive
      globus patients was sampled via the nasal cavity. Fucose and sialic acid, the
      determinants of the viscoelasticity of mucus, were measured. Twenty-three
      patients were also asked to complete the Throat Questionnaire so we could
      evaluate the correlation between the degree of globus sensation and the
      viscoelasticity of the mucus. The mucus of 10 healthy subjects was sampled,
      analyzed, and compared with the data of the patients. The fucose and sialic acid
      concentrations found in the patients with globus pharyngis were significantly
      higher than those in the control subjects (Mann-Whitney U test, p < .01). The
      fucose concentrations correlated significantly with the globus pharyngis scores
      (Spearman correlation, p < .05). We conclude that there is a close association
      between stagnant mucus in the epipharynx and globus sensation.

PMID- 12498375
TI  - Rat laryngeal transplant model: technical advancements and a redefined rejection
      grading system.
AB  - The rat laryngeal transplant model, introduced in 1992, laid the basic science
      foundation that contributed to the first successful human larynx transplant in
      1998. Over 1,500 rat transplants later, numerous modifications have improved the
      model, increasing the initially reported evaluability rate of 50% to almost 100%.
      The observed histologic rejection process has been altered, as well. We report
      the technique modifications, as well as the results of a new study using
      nonimmunosuppressed, allogenic transplantations, in order to define a new
      rejection grading system. Using the updated model, we performed 50
      transplantations between LBN(f1) donor rats and Lewis recipients. Larynges from 8
      groups of 5 to 10 animals were harvested at intervals between 1 and 20 days after
      transplantation. The larynges were examined grossly and microscopically in a
      blinded manner for evidence of rejection. A multivariable linear regression model
      was used to define a new rejection grading scale. All 50 animals survived their
      assigned posttransplantation period. No animals exhibited vascular thromboses,
      for an evaluability rate of 100%. Histologic criteria in 7 categories and gross
      criteria in 5 categories demonstrated increased rejection proportional to the
      amount of time after transplantation. The equation [Group = -2.209 + 0.465 x
      (Size) + 0.901 x (VA Flow) + 0.613 x (Muscle) + 1.040 x (Thyroid)] reproducibly
      grades rejection on the basis of gross and histologic findings. New modifications
      to the rat laryngeal transplant model have conferred greatly improved animal
      survival rates and anastomotic patency rates. Additionally, the observed rates of
      rejection have been reduced in comparison to those of initial studies. This
      updated rejection staging system will be used to compare immunosuppressive
      regimens in future rat laryngeal transplant studies.

PMID- 12498376
TI  - Effects of Clarion electrode design on mapping levels in children.
AB  - The design of the placement of the Clarion cochlear implant's intracochlear
      electrode array has undergone 2 revisions since its introduction, each to improve
      modiolar proximity. Stimulation with modiolar proximity may reduce current
      requirements for threshold levels and most comfortable levels of stimulation.
      This study analyzed the effects of electrode design on programming levels for
      deaf children implanted with the 3 cochlear implant designs and followed at The
      Children's Hospital of Philadelphia. Psychophysical data were reported if
      measurements were taken approximately 3 months after initial activation, and
      programming parameters included nonsequential monopolar stimulation of 75-micros
      per-phase biphasic pulses presented at 813 Hz per electrode. The threshold level
      and most comfortable programming level were measured by standard clinical
      techniques appropriate for children. The results indicate that the 2 electrode
      placement revisions have each significantly reduced threshold levels and most
      comfortable stimulation levels. These results are discussed in the context of
      device aesthetics, safety, and function.

PMID- 12498377
TI  - Localization of glucocorticoid receptors in the murine inner ear.
AB  - We performed an immunohistochemical investigation of the distribution of
      glucocorticoid receptors (GRs) in the murine inner ear and found that GRs were
      expressed extensively, but with various degrees of immunoreactivity in different
      regions. We observed the strongest GR expression in the type III fibrocytes of
      the spiral ligament. Although the immunoreactivity of the cochlear hair cells and
      of the vestibular sensory epithelia was weak, the neighboring cochlear supporting
      cells and the subepithelial regions of the vestibular sensory epithelia were
      immunostained. Staining for GRs was also positive in the spiral ganglia and
      vestibular ganglia, as well as in the endolymphatic sac. The role of GRs in the
      inner ear is discussed.

PMID- 12498378
TI  - Internet resources available to otolaryngologists.
AB  - During recent years, the Internet has evolved into the largest computer network
      in the world, allowing access to vast amounts of information and services.
      Medical information is increasingly available to both patients and professionals,
      and ever more biomedical resources are becoming available on-line to assist in
      research, clinical medicine, and education. The Internet has always provided
      useful resources to otolaryngologists, implemented at various academic
      departments and national organizations or by specialists or specific medical web
      sites offering technical, scientific, and biomedical information. The purpose of
      this article is to provide as complete a list as possible of the World Wide Web
      sites accessible through the Internet that are of interest to otolaryngologists.
      It summarizes different types of resources available, including educational
      material, audiology sites, outcomes research, discussion lists, research
      laboratories, publications, medical libraries, news and medical conferences,
      organizations, academic departments, otolaryngological and medical resources,
      medical and surgical equipment and suppliers, and miscellaneous other sites of
      interest to otolaryngologists. This review is intended to present the wealth of
      the accessible information on the Internet and to promote the use of the network
      to otolaryngologists who do not have extensive experience in computers or
      telecommunications.

PMID- 12498379
TI  - Voice and treatment outcome from phonosurgical management of early glottic
      cancer.
AB  - Phonosurgical management of early glottic cancer has evolved considerably, but
      objective vocal outcome data are sparse. A prospective clinical trial was done on
      32 patients with unilateral cancer (T1a in 28 and T2a in 4) who underwent
      ultranarrow-margin resection; 15 had resection superficial to the vocal ligament,
      and 17 deep to it. The subepithelial infusion technique facilitated selection of
      these patients for the appropriate procedure. All are cancer-free without
      radiotherapy or open surgery. Involvement of the anterior commissure (22/32) or
      the vocal process (15/32) of the arytenoid cartilage did not influence local
      control. Nine of 17 patients had resection of paraglottic musculature, and all
      underwent medialization reconstruction by lipoinjection and/or Gore-Tex
      laryngoplasty. Eight of the 17 had resections deep to the vocal ligament, but
      without vocalis muscle, and 1 of the 8 underwent medialization. Posttreatment
      vocal function measures were obtained for all patients. A clear majority of the
      patients displayed normal values for average fundamental frequency (72%) during
      connected speech, and normal noise-to-harmonics ratio (75%) and average glottal
      airflow (91%) measures during sustained vowels. Smaller majorities of patients
      displayed normal values for average sound pressure level (SPL; 59%) during
      connected speech and for maximum ranges for fundamental frequency (56%) and SPL
      (59%). Fewer than half of the patients displayed normal values for sustained
      vowel measures of jitter (45%), shimmer (22%), and maximum phonation time (34%).
      Almost all patients had elevated subglottal pressures and reduced values for the
      ratio of SPL to subglottal pressure (vocal efficiency). There were significant
      improvements in a majority of patients for most vocal function measures after
      medialization reconstruction. Normal or near-normal conversation-level voices
      were achieved in most cases, regardless of the disease depth, by utilization of a
      spectrum of resection and reconstruction options. These favorable results are
      based on establishing aerodynamic glottal competency and preserving the layered
      microstructure of noncancerous glottal tissue.

PMID- 12498380
TI  - Phonomicrosurgery in singers and performing artists: treatment outcomes,
      management theories, and future directions.
AB  - Phonomicrosurgery in performing artists has historically been approached with
      great trepidation, and vocal outcome data are sparse. The vocal liability of
      surgically disturbing the superficial lamina propria (SLP) and epithelium must be
      balanced with the inherent detrimental vocal effect of the lesion(s). A
      prospective investigation was performed on 185 performing artists who underwent
      phonomicrosurgical resection of 365 lesions: 201 nodules, 71 polyps, 66 varices
      and ectasias, 13 cysts, 8 keratotic lesions, 2 granulomas, 2 Reinke's edema, and
      2 papillomas. Nearly all patients with SLP lesions reported improvement in their
      postsurgical vocal function. This subjective result was supported by objective
      acoustic and aerodynamic measures. All postsurgical objective vocal function
      measures fell within normal limits, including a few that displayed presurgical
      abnormalities. However, given the relative insensitivity of standard objective
      measures to assess higher-level vocal performance-related factors, it is even
      more noteworthy that 8 of 24 objective measures displayed statistically
      significant postsurgical improvements in vocal function. Such changes in
      objective measures mostly reflect overall enhancement in the efficiency of voice
      production. Phonomicrosurgical resection of vocal fold lesions in performing
      artists is enjoying an expanding role because of a variety of improvements in
      diagnostic assessment, surgical instrumentation and techniques, and specialized
      rehabilitation. Most of these lesions are the result of phonotrauma and arise
      within the SLP. Successful management depends on prudent patient selection and
      counseling, ultraprecise technique, and vigorqus vocal rehabilitation.
      Furthermore, an understanding of the vocal function and dysfunction of this high
      performance population provides all otolaryngologists who manage laryngeal
      problems with valuable information that they can extrapolate for use in their
      practices.

PMID- 12498381
TI  - Cytokine responses to physical activity, with particular reference to IL-6:
      sources, actions, and clinical implications.
AB  - The present review examines the cytokine response to acute exercise stress, with
      particular emphasis on the balance between proinflammatory and anti-inflammatory
      mechanisms, and the release of IL-6. Prolonged endurance exercise induces a
      sequenced release of pro- and anti-inflammatory cytokines, and IL-6 plays a
      dominant role. The magnitude of this response bears a general relationship to the
      intensity of effort, but the duration of activity and many environmental factors
      also modulate cytokine release. Although many types of cells are capable of
      producing cytokines, the main source of the exercise-induced IL-6 production
      appears to be the exercising muscle. The primary function of the additional IL-6
      may be to regulate the supply of carbohydrate as muscle reserves of glycogen
      become depleted. There is also a delayed release of cytokines following eccentric
      exercise that is related to the repair of muscle injury. Since the production of
      cytokines is greater with endurance than with resistance exercise, it seems
      unlikely that they play an important role in the hypertrophy of muscle and bone.
      More research is needed on a number of important clinical issues where the
      exercise-induced release of cytokines may have relevance. Exercise-induced
      cytokine secretion has the potential to provide a simple model of sepsis.
      Preliminary observations suggest it may also modulate the risk of type 2 diabetes
      mellitus. Cytokine concentrations are increased in chronic fatigue syndrome,
      although it is less dear that the cytokine secretion is responsible for fatigue
      in humans. Exercise-induced modulations in cytokine secretion may contribute to
      allergies, bronchospasm, and upper respiratory infections in the endurance
      athlete. Further, the cytokine cascade is involved in the process of
      atherogenesis, and exercise-induced changes in cytokine production may expose
      latent HIV to chemotherapeutic agents.

PMID- 12498382
TI  - DNA target motifs of somatic mutagenesis in antibody genes.
AB  - During humoral immunity to T-cell-dependent antigens, responding B lymphocytes
      selectively mutate their antibody variable region genes at a high rate. This,
      together with the process of clonal selection, ultimately enhances the affinity
      and specificity of the antibody molecule and memory B cells that express it as a
      receptor. Despite several decades of investigation, the mutation mechanism has
      remained unresolved, largely due to the convoluted nature of experimental systems
      used to approach it. Somatic mutations preferentially occur within specific
      oligonudeotide motifs, and this targeting is consistent in all immunoglobulin
      genes of humans and mice that we have examined, suggesting that a conserved
      mechanism operates in both species. Our mutation targeting analyses implicate
      evolution of germline variable gene sequences to direct somatic mutations to
      specific codon positions in a manner that regulates the frequency of amino acid
      replacements to the benefit of the antibody product. Finally, our recent strand
      bias analyses support the idea that somatic mutation occurs preferentially,
      perhaps exclusively, at two bases on both strands of DNA. These and related
      observations from other laboratories support a mutation model that invokes at
      least two error-prone polymerases that have distinct template biases and
      requirements for elements of postreplicative mismatch repair.

PMID- 12498383
TI  - Immune function of the decoy receptor osteoprotegerin.
AB  - Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor (TNFR)
      superfamily. OPG has an important function as a protector of bone, demonstrated
      by the fact that OPG(-/-) mice have severe osteoporosis. OPG acts as a decoy
      receptor, binding to RANK ligand (RANKL), thus preventing the interaction between
      receptor activator of NF-kappaB (RANK) and RANKL. This interaction is required
      for the development of functionally active osteoclasts. Osteoclasts are cells of
      the monocytic lineage that are responsible for bone resportion. Furthermore, as
      well as being an important player in the regulation of bone metabolism, OPG also
      has a role in the regulation of the immune response. Dendritic cells (DCs)
      express RANK and T cells express RANKL. The ligation of RANK by RANKL can
      activate both T cells and DCs. Furthermore, both B cells and DCs secrete OPG, and
      this secretion is regulated by the CD40 receptor. OPG(-/-) mice have B-cell
      developmental defects. Also, DCs isolated from OPG(-/-) mice more efficiently
      present antigen in vitro and secrete elevated amounts of inflammatory cytokines
      when stimulated with bacterial products, or soluble RANKL in vitro. Taken
      together, this suggests that OPG plays an important role in the immune response
      regulating the interactions between T cells and DCs.

PMID- 12498384
TI  - Signal integration following Toll-like receptor triggering.
AB  - Innate immune cells sense infectious danger through recognition of pathogen
      associated molecular patterns (PAMP). Toll-like receptors (TLRs) play a pivotal
      role in the recognition of PAMP. Although various TLRs with distinct ligand
      specificities are expressed almost completely and contemporaneously by innate
      immune cells, and although central key signal transduction pathways of TLRs are
      shared, the innate response pattern is not uniform. Innate immune cells organize
      their response dependent on spatial and temporal requirements and mount a
      pathogen-specific and microbial-adopted reaction. Thus, after triggering of TLRs,
      complex signaling interactions take place that control and shape the reactivity
      patterns of innate immune cells. Here we discuss the central signaling pathways
      of TLRs and their interconnection with other signaling pathways, with emphasis on
      Janus kinases/signal transducers and activators of transcription JAK/STAT)
      dependent intracellular signals. Cis and trans acting signal convergence
      mechanisms and mutual influence of TLR and cytokine signaling pathways determine
      the response profile. Hence, in innate immune cells, integration and processing
      of microbial-dependent and immunologic signals is achieved within individual
      cells to ascertain an appropriate immune response. Knowledge of these complex
      mechanisms will help to clarify the critical events during initiation of
      infection, which in turn may lead to new strategies to control and overcome
      infectious disease.

PMID- 12498385
TI  - A murine model of bone marrow micrometastasis in breast cancer.
AB  - Bone marrow (BM) is one of the most common sites and often the first clinical
      indication of metastatic progression of breast cancer. Multivariate analyses have
      shown that the presence of cytokeratin positive tumor cells in the marrow of
      women with newly diagnosed stage I, II or III breast cancer is an independent
      predictor of survival. The objective of this study was to develop an orthotopic
      model of spontaneous BM metastasis to facilitate studies of this process. A
      murine mammary adenocarcinoma cell line, Clone 66, was transduced with the
      neomycin resistance gene (Cl66neo) and injected orthotopically into female Balb/c
      mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells
      harvested from tumor bearing mice demonstrated as few as 10(2) injected tumor
      cells produced BM micrometastases at 4 weeks postinjection. Small foci of tumor
      cells were identified in the mammary fatpad (mfp) without gross evidence of
      primary tumors. Higher doses of tumor cells produced BM micrometastases,
      detectable by PCR, at one week post-injection. Constructs containing green
      fluorescent protein (GFP) and the neomycin resistance gene (neo) were also
      transduced into Clone 66 cells (Cl66-GFPneo) and injected into the mfp. GFP
      transduced tumor cells were identified in multiple tissues in addition to BM by
      flow cytometric analysis (FACS) but less 13% of the animals developed gross
      metastases. This model is a clinically relevant tool for the analysis of organ
      specificity of metastasis.

PMID- 12498386
TI  - Quantification of human Alu sequences by real-time PCR--an improved method to
      measure therapeutic efficacy of anti-metastatic drugs in human xenotransplants.
AB  - For measuring the efficacy of new anti-metastatic drugs in preclinical models,
      macroscopical analysis or classical histology of secondary organs are established
      methods. However, macroscopical evaluation does not take into consideration intra
      organ metastasis. Histological analysis is often performed in few sections of the
      relevant organs, and this may be misleading, since equal distribution of tumor
      cells within an organ is unlikely. In addition, recent studies have demonstrated
      that anti-tumorigenic drugs are able to promote metastasis and to change the
      metastatic pattern. Therefore, extensive analysis of metastasis is mandatory for
      the evaluation of new compounds. A feasibility study was conducted to find out if
      the quantification of human Alu sequences could be applied as a surrogate marker
      for metastasis in xenografts. Alu PCR was performed by using the LightCycler
      system, which allows PCR reaction and subsequent quantification of the PCR
      products in less than 30 min. We found that i) the equivalent of one human tumor
      cell in 1 x 10(6) murine cells could be detected; ii) in tumor-carrying mice, Alu
      signal increased over time in secondary organs; iii) this increase was more
      prominent using highly metastatic tumor cells; iv) Alu signal intensity in DNA
      extracted from tissue slides correlated with the expression of histological tumor
      markers; v) in three different tumor models (colon, breast and lung), treatment
      with Taxol or 5-fluorouracil reduced the amount of Alu in different organs. In
      contrast, reduction of Alu by the matrix metalloproteinase inhibitor RO 28-2653
      was not significant. Taken together, quantification of Alu sequences is a fast
      and accurate method to evaluate the therapeutic efficacy of anti-metastatic drugs
      in xenografts.

PMID- 12498387
TI  - Mechanisms involved in the differential bone marrow homing of CD45 subsets in 5T
      murine models of myeloma.
AB  - Multiple myeloma (MM) is an incurable plasma cell cancer, localized in the bone
      marrow (BM). The mechanisms used by these cells to (re-)enter this organ remain
      largely unknown. Recently, we reported that both CD45+ and CD45- myeloma cells
      home to the BM and induce myeloma disease. In this work, we investigated the
      underlying mechanisms involved in the homing of CD45+ and CD45- myeloma cells in
      the experimental 5T2MM and 5T33MM murine models. In vivo tracing of flow
      cytometric sorted and radioactively labeled CD45 subsets revealed a reduced
      homing of the CD45- 5TMM cells to the BM as compared to the CD45+ 5TMM cells.
      Migration assays demonstrated an impaired chemotaxis towards BM endothelial cell
      conditioned medium, BM stromal cell conditioned medium and towards the basement
      membrane component laminin-1 of the CD45- 5TMM cells compared to the CD45+
      subset. Matrix metalloproteinase-9 (MMP-9) and urokinase type plasminogen
      activator (uPA) are key extracellular matrix proteases involved in the invasion
      of cancer cells. Inhibitor and antibody blocking experiments demonstrated the
      involvement of both in the invasion of the 5TMM cells. CD45- 5TMM cells had a low
      secretion of MMP-9 and (for the non-aggressive line 5T2MM only) a low cell
      surface expression of uPA receptor, as revealed by gelatin zymography and flow
      cytometric analysis, respectively. Accordingly, the synthetic basement membrane
      invasive capacity of the CD45- 5TMM subpopulations was also impaired. Our results
      indicate that CD45+ and CD45- 5T myeloma cells have a differential BM homing
      attributable to differential migratory and invasive capacities.

PMID- 12498388
TI  - Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate
      cancer cell invasion.
AB  - The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to
      investigate the correlation of the COX-2 expression and its arachidonic acid
      metabolites, prostaglandins, with their invasiveness through Matrigel using a
      Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was
      approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1
      expression was similar in both cell sublines. When incubated with arachidonic
      acid, PGE2 was the major prostaglandin produced by these cells. PC-3 High
      Invasive cells produced PGE2 approximately 2.5-fold higher than PC-3 Low Invasive
      cells. PGD2 was the second most abundant prostaglandin produced by these cells.
      Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2
      inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE2
      alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE2
      reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion
      of the PC-3 High Invasive cells. In contrast, PGD2 slightly inhibited the cell
      invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2
      derived PGE2 may not be sufficient to induce cell invasion while in the PC-3 High
      Invasive cells, PGE2 may be sufficient to act as an enhancer for the cell
      invasion. Further, PGD2 may represent a weak inhibitor and counteracts the effect
      of PGE2 in the cell invasion.

PMID- 12498389
TI  - Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast
      cancer cells.
AB  - Autotaxin (ATX), originally isolated from human melanoma cells, is a novel
      metastasis-enhancing motogen and angiogenesis factor. In the present study, we
      compared the expression level of ATX mRNA between normal and breast cancer
      tissues and found that the expression of ATX mRNA was closely linked to
      invasiveness of cancer cells. Reverse transcriptase-polymerase chain reaction (RT
      PCR) and immunohistochemical analysis showed higher cellular ATX mRNA expression
      in the cancer than normal breast tissues. MDA-MB-435S breast cancer cells,
      expressing higher amount of ATX mRNA, showed greater relative invasiveness to
      fibroblast-conditioned medium (FCM) than MCF7, MDA-MB-231, and HBL-100 breast
      cancer cells. Furthermore, ATX-transfected MCF7 cells showed increased motility
      and invasiveness than vector-transfected MCF7 cells. Collectively, our results
      suggest that the expression of ATX is closely linked to the invasiveness of
      breast cancer cells.

PMID- 12498390
TI  - Evidence for the causal role of endogenous interferon-alpha/beta in the
      regulation of angiogenesis, tumorigenicity, and metastasis of cutaneous
      neoplasms.
AB  - Primary tumor growth and metastasis depend on angiogenesis, which is determined
      by the balance between proangiogenic and antiangiogenic molecules. Interferon
      (IFN)-alpha and -beta inhibit angiogenesis through downregulation of interleukin
      8, matrix metalloproteinase-9, and basic fibroblast growth factor. To provide
      evidence for the causal role of IFN-alpha/beta in the induction of neoplasms,
      their angiogenesis, and hence, progressive growth, we carried out experiments
      using 129S6 IFN-alpha/beta receptor -/- mice back-crossed to BALB/c nude mice.
      Subcutaneous angiogenesis was determined following implantation of gelfoam
      sponges containing 0.4% agarose and several proangiogenic molecules.
      Tumorigenicity and production of lung metastasis were determined subsequent to
      subcutaneous and intravenous injections, respectively, of highly metastatic
      A375SM human melanoma cells. Carcinogenesis was induced by chronic exposure of
      mice to UVB radiation (5 kJ/m2, 3 times/week). Angiogenesis, tumorigenicity, and
      production of metastasis, as well as development of autochthonous skin tumors,
      were all accelerated in IFN-alpha/beta receptor -/- mice as compared to control
      mice. Collectively, the data show that inability to respond to endogenous IFN
      alpha/beta (through a mutation in the IFN-alpha/beta receptor) leads to increased
      susceptibility to carcinogenesis, enhanced angiogenesis, tumorigenicity, and
      metastasis.

PMID- 12498391
TI  - Immunomagnetic enrichment and detection of isolated tumor cells in bone marrow of
      patients with epithelial malignancies.
AB  - The detection of isolated tumor cells (ITC) in the bone marrow of patients with
      epithelial malignancies is an independant prognostic factor for several entities
      as breast cancer, colorectal cancer or non-small lung cancer. However, with
      conventional immunocytology using Ficoll density gradient and APAAP staining,
      only a small proportion of the bone marrow samples can be scanned for cytokeratin
      positive (CK+) cells. To improve detection rates, we evaluated the enrichment of
      ITC by magnetic activated cell sorting (MACS) compared to regularly stained
      cytospins. Recovery experiments with a CK+ breast cancer cell line (SKBR3) were
      performed to calculate the MACS enrichment rate. Bone marrow was obtained by
      aspiration from 20 patients with carcinomas of epithelial origin and from 17
      controls. ITC were enriched and stained with magnetically labeled CAM 5.2
      antibodies directed to cytokeratin 7 and 8. MACS of SKBR3 seeded in peripheral
      blood revealed average recovery rates of 62% and 48% and average enrichment
      factors of 104-fold and 8139-fold of the CK+ cells after one and after two
      separations, respectively. After immunomagnetic enrichment, CK+ cells were
      detected in 16 of 20 (80%) cancer patients, whereas only 7 (35%) patients showed
      CK+ cells without magnetic enrichment (P = 0.002). Ten of twelve (83%) patients
      with metastatic disease (stage M1) and six of eight (75%) patients without any
      overt metastases (M0) had CK+ cells in their bone marrow. None of the negative
      controls showed any CK+ cells. Enrichment with magnetically labeled anti
      cytokeratin antibodies increases the detection rate of epithelial cells in bone
      marrow of cancer patients compared to immunocytology.

PMID- 12498392
TI  - Increased resistance towards oxidative stress accompanies enhancement of
      metastatic potential obtained by repeated in vivo passage of colon carcinoma
      cells in syngeneic rats.
AB  - The colon carcinoma cell line CC531 is metastatic to liver after splenic
      injection in syngeneic rats. After repeated in vivo passages, a subline was
      selected that produced liver metastases at a considerably higher rate than the
      original cell line. These cells were characterized by increased intracellular
      glutathione, proliferation and ability to restore glutathione after exposure to
      oxidative stress, thus indicating an elevated resistance to oxidative stress.
      Furthermore, the increased metastatic ability was also accompanied by increased
      proliferation rate, adhesion to extracellular matrix proteins and endothelial
      cells, and secretion of a 60 kD matrix metalloproteinase. When cultured in vitro
      for a prolonged time (more than 30 trypsinizations), the cells showed a reduced
      in vivo metastatic ability, reduced secretion of three metalloproteinases
      including the 60 kD proteinase, and reduced intracellular glutathione. These
      results indicate that metastatic ability can be influenced through several
      adaptive mechanisms, and that the cell's ability to resist oxidative stress and
      maintain intracellular glutathione are of central importance.

PMID- 12498393
TI  - Redistribution of fibroblasts and macrophages as micrometastases develop into
      established liver metastases.
AB  - Fibroblastic tissue is an important component of malignant tumors, involved in
      the establishment of metastatic foci from micrometastases, and thought to prevent
      invasion of metastatic tumor cells into surrounding tissue. However, experimental
      models of fibrosis during the growth of micrometastasis into established
      metastases were not previously available. In the present paper, we performed
      immunohistochemical studies on experimental hepatic metastasis with colon 38
      mouse colon carcinoma cells injected into syngeneic C57BL/6 mice. Early and late
      stages of metastatic nodules were examined for the distribution of endothelial
      cells, fibroblasts, and macrophages by the use of markers of these cells. One
      week after intrasplenic injection of colon 38 cells, micrometastases mainly
      appeared in the region of sinusoids accompanied with invasion of F4/80-positive
      Kupffer cells. Transitional metastases can be defined based on the histological
      appearance and intensive infiltration of both macrophages and fibroblasts. These
      transitional metastases were connected by protrusions of fibroblast-rich tissues
      co-localized with collagen-rich matrix and CD31-positive cells. This protrusion
      preceded fibrosis formation characteristics to established metastases associated
      with angiogenesis and segregation of tumor cells from host cells. Three stages
      can thus be classified during the development of hepatic metastasis in this
      syngeneic experimental system: micrometastasis, transitional metastasis, and
      established metastasis.

PMID- 12498395
TI  - Seeking security--weapons or words.

PMID- 12498394
TI  - Deregulated activation of matriptase in breast cancer cells.
AB  - Matriptase is an epithelial-derived, cell surface serine protease. This protease
      activates hepatocyte growth factor (HGF) and urokinase plasminogen activator
      (uPA), two proteins thought to be involved in the growth and motility of cancer
      cells, particularly carcinomas, and in the vascularization of tumors. Thus,
      matriptase may play an important role in the progression of carcinomas, such as
      breast cancer. We examined the regulation of activation of matriptase in human
      breast cancer cells, in comparison to non-transformed mammary epithelial cells
      184A1N4 and MCF-10A. Results clearly indicated that unlike non-transformed
      mammary epithelial cells, breast cancer cells do not respond to the known
      activators of matriptase, serum and sphingosine 1-phosphate (S1P). Similar levels
      of activated matriptase were detected in breast cancer cells, grown in the
      presence or absence of S1P. However, up to five-fold higher levels of activated
      matriptase were detected in the conditioned media from the cancer cells grown in
      the absence of serum and S1P, when compared to non-transformed mammary epithelial
      cells. S1P also induces formation of cortical actin structures in non-transformed
      cells, but not in breast cancer cells. These results show that in non-transformed
      cells, S1P induces a rearrangement of the actin cytoskeleton and stimulates
      proteolytic activity on cell surfaces. In contrast, S1P treatment of breast
      cancer cells does not activate matriptase, and instead these cells constitutively
      activate the protease. In addition, breast cancer cells respond differently to
      S1P in terms of the regulation of actin cytoskeletal structures. Matriptase and
      its cognate inhibitor, HGF activator inhibitor 1 (HAI-1) colocalize on the cell
      periphery of breast cancer cells and form stable complexes in the extracellular
      milieu, suggesting that the inhibitor serves to prevent undesired proteolysis in
      these cells. Finally, we demonstrate that treatment of T-47D cells with epidermal
      growth factor (EGF), which promotes cell ruffling, stimulates increased
      accumulation of activated matriptase at the sites of membrane ruffling,
      suggesting a possible functional role at these sites.

PMID- 12498396
TI  - The United Nations: the embarrassment of international law.
AB  - The United Nations should be working towards an international community living in
      peace under the aegis of international law. Although progress was made in its
      early years, notably in decolonization, with its membership increased from 50 to
      189, major inequalities remain between its nations and their peoples. The
      Security Council, and in particular its five permanent members (P5), has been
      guilty of double standards in enforcing international law. Investment should
      create prosperity and not increase demand for arms. Independent oversight of the
      UN, and particularly the Security Council, by civil society is needed. If the
      legitimacy of the UN is to be restored, the Security Council should become more
      representative, the power of the General Assembly should be restored and the role
      of the International Court of Justice should be increased. All members of the UN,
      especially the PS, must respect international law as enshrined in the UN Charter
      and Conventions.

PMID- 12498397
TI  - Aiming for Prevention: international medical conference on small arms, gun
      violence and injury.
AB  - IPPNW and Physicians for Social Responsibility, Finland organized an
      international conference on small arms and firearms injury in Helsinki from 28-30
      September 2001, emphasizing the preventive medicine aspects of the issues
      discussed. This article describes the background to this conference and reports
      the work of IPPNW in following it up.

PMID- 12498398
TI  - Small arms, physicians and politics.
AB  - Figures for deaths from private use of small arms, particularly in children and
      young people, are summarized and responses to the discussion of these figures in
      a recent editorial in the British Medical Journal are considered. It is contended
      that the figures highlight a major public health problem, particularly in the
      United States. Further, this article emphasizes that the politicization of the
      debate by the US gun lobby should not be allowed to obscure the conflict-related
      consequences of small arms in the developing world.

PMID- 12498399
TI  - More guns, more deaths.
AB  - It is contended that easier access to small arms increases the likelihood of
      misuse, on the basis of evidence comparing rates of firearm mortality and
      availability both between comparably developed countries, contrasting
      particularly the United States and others, and in different regions of individual
      countries. For example, firearm mortality is often greater in rural areas than
      urban. Possible inaccuracies in data collection are considered, but felt not
      sufficient to account for the finding. Measures to restrict availability such as
      stricter licensing, regulations governing storage and legally-imposed 'gun-free
      zones' may all reduce the death toll. In conflict zones, measures to remove arms
      post-conflict reduce subsequent mortality. Breaking the supply chain is also
      important and the link between supply, demand and the values of a society must be
      kept in mind.

PMID- 12498400
TI  - The value of credible data from under-resourced areas.
AB  - Data collection requires a substantial investment in human resources and
      infrastructure, but it is essential that it is accurate to ensure the credibility
      of its use. These issues are explored in the light of data from injuries in
      'disorganized' settings based on the experiences of field hospitals staffed by
      the International Committee of the Red Cross. Such data was influential in the
      campaign to ban landmines and can be used in the legitimate questioning of
      states' foreign policies. It is important to distinguish between combatant and
      non-combatant weapons injuries. A significant proportion of civilian weapons
      injuries in combat zones, particularly post-conflict, occur in a domestic
      context; some widely quoted figures for civilian war-related injuries are too
      high, though the correct figures are still far too high. While reducing the
      supply of arms, the importance of other social factors such as education, poverty
      and the provision of health care is stressed-provision of health care is affected
      in combat zones.

PMID- 12498401
TI  - The physician's role in preventing small arms injury.
AB  - The first step in defining a public health problem is to describe its scope and
      nature. For most diseases, this involves details on the victims, morbidity and
      mortality, and the agent of the disease. In the case of the small-arms 'disease',
      apart from data on the injuries caused, most other information resides with
      criminal justice agencies that are primarily concerned with criminal activity. In
      the United States, beginning in the state of Wisconsin, an approach based on the
      nation-wide data system of car crash deaths has been developed, linking medical
      examiners, coroners, police data and other information to provide a comprehensive
      picture of firearm-related deaths. The next step should be to develop
      standardized firearm-markings that would aid in controlling the illicit trade in
      small arms and more detailed information on the relationship between type of
      firearm and injury. Physicians can do much to aid prevention of small arms injury
      by advocating this public health approach.

PMID- 12498402
TI  - The effects of war on the Colombian population.
AB  - In the last decade, more than 1.5 million children have died as victims of war
      and 2000 over 300,000 children were being used as combatants. Colombia, the
      fourth largest country in Latin America in terms of population and second in
      area, has been the site of conflict between the government and guerrilla groups,
      which has created over 200,000 victims and has worsened in the last five years.
      There is severe poverty and illegal trading in arms and narcotics is closely
      linked to the conflict. Kidnapping, both individual and mass and often of
      children, has been a particular feature. Colombia urgently needs programmes to
      eradicate poverty and violence and must be fully supported by international
      organizations. Research to suggest effective interventions is an essential part
      of such programmes.

PMID- 12498403
TI  - The relationship between human security, demand for arms and disarmament in the
      horn of Africa.
AB  - The drive to find security through possession of weapons is linked to the history
      and culture of a social group. Amongst pastoralists in the Horn of Africa there
      is a failure of security through state systems such as police and the recent
      replacement of less-lethal traditional weapons by small arms and other light
      weapons. A warrior or vendetta culture with these arms leads to violent inter
      clan clashes with many casualties, although traditional methods of weapons
      control still seem operational within clans. Understanding the drive to seek
      weapons is essential in finding ways to control their use. Improving the
      capacities of the police must come hand in hand with human rights training and an
      end to corruption. Further work is required on how traditional methods of arms
      control can be co-operatively linked with state controls.

PMID- 12498404
TI  - Guns, health and the exploitation of natural resources.
AB  - There are about 1 million small arms in Nigeria, which contribute to a large
      number of politically motivated killings. These are mainly sectarian (Christian
      and Muslim) and ethnic, over land and water rights and the relationship between
      the activities of companies and the environment. In the Ogoni region of the Niger
      Delta, with a population of half a million in an area of just over 400 square
      miles, there are 100 oil wells; the local community is attempting non-violently
      to clean up their environment. From July 1993 to April 1994 there were about
      3,000 cases of gun violence, compared with only two in the previous five years.
      There were 250 deaths and about 100 amputations. Other forms of violence,
      including rape, also increased. Routine procedures in the hospitals that remained
      open were disrupted, there were serious effects on the mental health of the
      community and many became refugees. It appears that the guns used in this episode
      were imported by a multinational company for use by the Nigerian police.

PMID- 12498405
TI  - Summit for survival: International Physicians for Prevention of Nuclear War XVth
      World Congress.

PMID- 12498406
TI  - Putting the art into veterinary practice.

PMID- 12498407
TI  - Effects of epidural injections and transvaginal aspiration of ovarian follicles
      in heifers used repeatedly for ultrasound-guided retrieval of ova and embryo
      production.
AB  - Postmortem examinations of 13 Simmental heifers that had received between 16 and
      28 injections to induce caudal epidural anaesthesia, the last not less than seven
      months before they were slaughtered, showed that none of them had any evidence of
      infection or inflammation at the injection site or in adjacent bone and soft
      tissues. Seven of them had minor damage to intercoccygeal discs, consisting of
      discospondylosis with neovascularisation and chondroid metaplasia, consistent
      with injuries caused by needles. The severity of the damage was not related to
      the number of epidural injections received, suggesting that the damage was
      probably caused by a discrete suboptimal injection procedure. In a second study,
      the ovaries from 22 Simmental heifers that had undergone between 13 and 16
      transvaginal follicular aspirations were examined postmortem. Approximately one
      third of them had a natural texture with little or no evidence of scar tissue,
      and less than one in five had extensive scarring and a toughened texture. There
      was no evidence of compromised ovarian function, as determined by the number and
      normality of corpora lutea and large follicles, in any of the animals.

PMID- 12498408
TI  - Study of crib-biting and gastric inflammation and ulceration in young horses.
AB  - Nineteen young horses that had recently started to perform the stereotypy of crib
      biting were compared with 16 non-stereotypic horses for 14 weeks. After initial
      observations of their behaviour and an endoscopic examination of the condition of
      their stomachs, the horses were randomly allocated to a control or an antacid
      diet At the start of the trial, the stomachs of the crib-biting foals were
      significantly more ulcerated and inflamed than the stomachs of the normal foals.
      In addition, the faecal pH of the crib-biting foals (6.05) was significantly
      lower than that of the normal foals (6.58). The antacid diet resulted in a
      significant improvement in the condition of the horses' stomachs. The crib-biting
      behaviour declined in most of the foals, regardless of their diet, but tended to
      decline to a greater extent in the foals on the antacid diet.

PMID- 12498409
TI  - Vitamin E deficiency in dogs with retinal pigment epithelial dystrophy.
AB  - The role of vitamin E deficiency in the development of retinal pigment epithelial
      dystrophy was investigated in 11 cocker spaniels and four other dogs. The
      concentration of alpha-tocopherol was measured by high performance liquid
      chromatography in plasma samples obtained from the affected dogs and from 28
      ophthalmoscopically normal, healthy control dogs. The mean (sd) plasma alpha
      tocopherol concentration in the normal dogs was 20.2 (7.1) microg/ml, compared
      with 1.14 (0.67) microg/ml in the 11 affected cocker spaniels. The difference
      between the two groups remained highly significant when the alpha-tocopherol
      concentrations were expressed relative to the concentrations of the plasma lipids
      cholesterol and triglycerides. Low plasma concentrations of alpha-tocopherol were
      observed in the four affected dogs of other breeds, but the finding was not so
      consistent. The plasma lipid concentrations were normal in the affected dogs. The
      deficiency of alpha-tocopherol in the affected dogs appeared to be primary,
      because there was no clinical, biochemical or pathological evidence of underlying
      disease, or any indication of a dietary deficiency which might have contributed
      to the low concentrations of alpha-tocopherol.

PMID- 12498410
TI  - Review of foot-and-mouth disease virus survival in animal excretions and on
      fomites.

PMID- 12498411
TI  - DNA macrorestriction analysis by pulsed-field gel electrophoresis of Pseudomonas
      aeruginosa isolates from mastitis in dairy sheep.

PMID- 12498412
TI  - Equine renal granuloma caused by Halicephalobus species.

PMID- 12498413
TI  - Human case of EBL type 2 following exposure to bats in Angus, Scotland.

PMID- 12498414
TI  - Ewe genotyping.

PMID- 12498415
TI  - Competition Commission inquiry into POMs.

PMID- 12498416
TI  - Competition Commission inquiry into POMs.

PMID- 12498417
TI  - FMD control strategies.

PMID- 12498418
TI  - Encephalitozoon cuniculi in rabbits.

PMID- 12498419
TI  - Cell-free fetal DNA and intact fetal cells in maternal blood circulation:
      implications for first and second trimester non-invasive prenatal diagnosis.
AB  - Both intact fetal cells as well as cell-free fetal DNA are present in the
      maternal circulation and can be recovered for non-invasive prenatal genetic
      diagnosis. Although methods for enrichment and isolation of rare intact fetal
      cells have been challenging, diagnosis of fetal chromosomal aneuploidy including
      trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50
      75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from
      maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and
      paternally derived single gene mutations. Real-time PCR assays are robust in
      detecting low-level fetal DNA concentrations, with sensitivity of approximately
      95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free
      fetal DNA methods for non-invasive prenatal screening for fetal chromosomal
      aneuploidy reveals that the latter is at least four times more sensitive. These
      preliminary results do not support a relationship between frequency of intact
      fetal cells and concentration of cell-free fetal DNA. The above results imply
      that the concentration of fetal DNA in maternal plasma may not be dependent on
      circulating intact fetal cells but rather be a product of growth and cellular
      turnover during embryonic or fetal development.

PMID- 12498420
TI  - Fetal cells and cell-free fetal DNA in maternal blood: new insights into pre
      eclampsia.
AB  - The examination of fetal cells, specifically erythroblasts, and cell-free fetal
      DNA from the blood of pregnant women is currently the subject of intense research
      with the aim of developing new risk-free methods for prenatal diagnosis. An
      unexpected finding made during these studies was that the traffic of fetal
      erythroblasts into the maternal peripheral circulation was enhanced in pre
      eclampsia. Independent prospective studies examining samples collected in the
      second trimester indicated that this perturbation in fetal cell trafficking
      occurs early in pregnancy, well before the onset of pre-eclampsia symptoms. The
      quantitative analysis of cell-free fetal and maternal DNA levels indicated that
      these concentrations were elevated in a co-ordinate manner in manifest pre
      eclampsia, and that these elevations corresponded to disease severity. On the
      other hand, analysis of prospectively collected samples indicated that only cell
      free fetal but not maternal DNA levels were elevated before onset of symptoms in
      pregnancies which subsequently developed pre-eclampsia. These data support
      hypotheses suggesting that pre-eclampsia is a multi-step disorder, initiated by a
      placental lesion that occurs early in pregnancy and which subsequently leads to a
      systemic maternal inflammatory response and associated endothelial cell damage.

PMID- 12498421
TI  - Strategies for automated fetal cell screening.
AB  - Studies to date have demonstrated fetal sex determination and aneuploidy
      detection from maternal blood, but a clinical screening technique has not yet
      emerged. A key limiting factor is the small number of fetal cells, which makes
      detection specificity and reliability critical. Visual inspection of unsorted or
      sorted fetal cells is laborious, and cells can be easily missed. Moreover, it is
      impractical to examine manually all the separated cells. It is highly likely that
      automation may increase the number of cells inspected, resulting in higher
      detection sensitivities. Flow and image cytometry are two feasible approaches for
      automated detection of cells. This review details computerized microscopy (image
      cytometry) techniques for the automatic detection of fetal cells. Microscopy
      based approaches used to identify fetal origin include: (i) immunocytochemical
      identification of fetal haemoglobin-specific cells (light or fluorescence
      microscopy); (ii) identification of sex chromosomes and/or aneuploidy using
      fluorescence in-situ hybridization; and (iii) morphological identification of
      nucleated red blood cells using light microscopy. The relevant instrumentation,
      including motorized stages and filters, cameras and digitizer boards are
      discussed, and software algorithms, including image enhancement, autofocusing,
      object detection and relocation, and features for operator review and data
      analysis, are outlined.

PMID- 12498422
TI  - Culture of fetal cells from maternal blood for prenatal diagnosis.
AB  - The isolation and analysis of fetal cells from maternal blood would allow non
      invasive prenatal genetic screening and diagnosis. Over the past decade, progress
      has been made towards this goal using various enrichment strategies and analysis
      by fluorescence in-situ hybridization with chromosome-specific probes and PCR.
      One method that is currently being explored involves culturing fetal cells.
      Developing conditions which allow the number of fetal-derived cells to expand in
      culture and the number of maternally derived cells to be suppressed in culture
      may lead to a new selection process for obtaining fetal cells. Culturing of fetal
      cells from maternal blood could make possible conventional metaphase analysis of
      fetal cells for diagnosis of chromosomal abnormalities.

PMID- 12498423
TI  - Inhibins, activins and follistatin in reproduction.
AB  - The regulation of reproductive processes involves a complex network of
      communication systems between the brain, endocrine organs, the gonads and other
      reproductive tissues. Classically, our understanding has focused on the role of
      endocrine hormones, but more recently interest has also dwelt on the paracrine
      and autocrine regulation of these cell systems. In this review, the structure and
      physiology of the inhibins, activins and follistatin are discussed in terms of
      the evidence supporting their role as endocrine hormones, and how they might
      function as paracrine factors within the pituitary, gonad and associated tissues.
      With the advent of more specific techniques and assays for their measurement, the
      potential of inhibins, activins and follistatin as clinical markers of
      reproductive function and in the screening of various pathologies is also
      evaluated.

PMID- 12498424
TI  - The use of LH activity to drive folliculogenesis: exploring uncharted territories
      in ovulation induction.
AB  - LH plays critical roles in the control of folliculogenesis and ovarian function
      in humans. LH activity administration during gonadotrophin ovulation induction
      can enhance ovarian response and optimise treatment. More specifically, LH
      activity (both LH and low-dose hCG) can support the growth and stimulate the
      maturation of larger ovarian follicles as a result of specific granulosa cell
      receptors that develop after a few days of FSH priming. This action of LH is
      independent of FSH, and it has been shown recently that the last stages of
      follicular development can be supported by sole administration of LH activity in
      the form of low-dose hCG, without causing premature luteinization. Reproductively
      competent oocytes and pregnancy can be obtained with this regimen. Furthermore,
      LH activity is capable of reducing the development of small ovarian follicles
      (<10 mm) that may predispose patients to developing complications such as the
      ovarian hyperstimulation syndrome. Thus, better understanding of the dynamics and
      mechanisms that control human folliculogenesis and a more rational and selective
      use of LH activity administration may allow a reduction in cost and increased
      safety, while maintaining a high efficacy of the ovulation induction regimens
      used in assisted reproduction.

PMID- 12498425
TI  - Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a
      review.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic complication of
      ovarian stimulation occurring during the luteal phase or during early pregnancy.
      Fortunately, the reported prevalence of the severe form of OHSS is small, ranging
      from 0.5 to 5%. Nevertheless, as this is an iatrogenic complication of a non
      vital treatment with a potentially fatal outcome, the syndrome remains a serious
      problem for specialists dealing with infertility. The aim of this literature
      review was to determine whether it is possible to identify patients at risk, and
      which preventive method should be applied when an exaggerated ovarian response
      occurs. Data pertaining to the epidemiology and prevention of OHSS in women were
      searched using Medline, Current Contents and PubMed, and are summarized.
      Preventive strategies attempt either to limit the dose or concentration of hCG or
      to find a way to induce luteolysis without inducing a detrimental effect on
      endometrial and oocyte quality. The following particular preventive strategies
      were reviewed: cancelling the cycle; coasting; early unilateral ovarian
      follicular aspiration (EUFA); modifying the methods of ovulation triggering;
      administration of glucocorticoids, macromolecules and progesterone;
      cryopreservation of all embryos; and electrocautery or laser vaporization of one
      or both ovaries.

PMID- 12498426
TI  - Child development and quality of parenting in lesbian families: no psychosocial
      indications for a-priori withholding of infertility treatment. A systematic
      review.
AB  - Among fertility centres, much discussion focuses on whether to withhold
      infertility treatment from special patient groups (lesbians, prospective single
      parent(s), prospective parent(s) of relatively advanced age, or with severe
      diseases) because it is assumed that this is in the best interest of the child.
      The present study aimed to establish whether there is any empirical evidence for
      this assumption. A literature search was made in PubMed/Medline and PsycINFO to
      identify studies that had assessed psychological outcomes of children and quality
      of parenting after infertility treatment. Eight studies met the following
      inclusion criteria: published in an English-language peer-reviewed journal
      between 1978 and 2002, and focused on psychosocial child development and quality
      of parenting after infertility treatment in the above-mentioned special patient
      groups. All reviewed studies focused on lesbian or single-parent families.
      Overall, the methodological quality of studies as assessed by a standardized set
      of criteria was high. The evidence of the studies (assessed by the best evidence
      synthesis method) was strong for the conclusion that in lesbian families the
      psychosocial development of children (median age 6.1 years) and the quality of
      parenting are not different from those in healthy heterosexual two-parent
      families after infertility treatment or natural conception. Therefore,
      withholding infertility treatment from lesbian families on the assumption that
      such intervention may not be in the interest of the prospective child seems
      unjustified. For the other special patient groups, no conclusions could be drawn,
      because of a lack of relevant studies.

PMID- 12498428
TI  - Preserving proven concepts in implant dentistry.

PMID- 12498427
TI  - Management of ovarian endometriomas.
AB  - The efficiency of medical therapy as a unique treatment for endometrioma has not
      been demonstrated. Operative laparoscopic management is the 'gold standard' for
      surgical treatment, and there are no indications to prescribe medical treatment
      before cystectomy. Post-operative administration of low-dose cyclic oral
      contraceptives does not significantly affect the long-term recurrence of
      endometriosis after surgical treatment. In case of infertility, the management of
      endometriomas is controversial. Recurrent ovarian surgery is not recommended.

PMID- 12498429
TI  - The effect of implant diameter, restoration design, and occlusal table variations
      on screw loosening of posterior single-tooth implant restorations.
AB  - The purpose of this study was to (1) determine in vitro the effect of narrowing
      the buccolingual width of the occlusal table on the untightening torque required
      to loosen gold prosthetic screws after subjecting implants and implant-supported
      restorations to occlusal loads, and (2) to compare the incidence of screw
      loosening and values of untightening torque of the screws among crowns supported
      by 1 wide-diameter as opposed to 2 standard implants after loading in vitro. The
      restorations were divided into 4 groups (group 1, a narrow crown supported by one
      5-mm wide-diameter implant; group 2, a narrow crown supported by 2 standard 3.75
      mm-diameter implants; group 3, a wide crown supported by one 5-mm wide-diameter
      implant; and group 4, a wide crown supported by 2 standard 3.75-mm-diameter
      implants). A custom-designed chewing machine was used to simulate the grinding
      phase of the masticatory cycle and lateral excursions. The crowns were subjected
      to a 6-kg load for 16660 cycles over 5.5 hours and were loaded at the outer and
      inner inclines and cusp tips with an untightening loading pattern. The
      untightening torque was measured for the gold screws in the different groups
      before and after loading at 4 different locations for 8 cycles on the simulated
      chewing machine. A 1-way analysis of variance indicated a significant difference
      (P < .001) among the test groups. Pairwise multiple comparison tests (Scheffe)
      were carried out on mean "change scores." Group 3 was significantly different
      from the other groups, which were not significantly different from each other.
      Restoring missing molars with 1 wide-diameter implant had a greater incidence of
      screw loosening as compared with 2 implants. Narrowing the occlusal table of the
      restoration is critical when using 1 implant to support a missing molar. The
      untightening torque of gold screws was not affected by changing the width of the
      occlusal table of crowns supported by 2 implants.

PMID- 12498430
TI  - Minimally invasive implant surgery.
AB  - The use of dental implants in the esthetic zone is a viable alternative to the
      traditional fixed partial denture A modification of the Tatum bone expansion
      technique is described as an option for patients considering the replacement of 1
      or more missing maxillary incisors.

PMID- 12498431
TI  - An overview of the Lew attachment: clinical reports.
AB  - Although the Lew attachment was originally developed to provide retention for
      overdentures fabricated in conjunction with subperiosteal implants, these
      attachments can also be used with other types of implants. Two cases are
      presented to describe the use of Lew attachments, one with a conventional
      subperiosteal implant, and the other with 4 endosteal implants and an implant
      connecting bar.

PMID- 12498432
TI  - The use of ramus bone cores for maxillary sinus bone grafting: a surgical
      technique.
AB  - The study describes a surgical technique for the use of ramus bone cores
      routinely used in the surgical rebuilding of deficient maxillary sinuses. The
      bone core harvest is predictable and without significant morbidity to the
      patient. There is clinical evidence to suggest this technique may significantly
      speed up the process of building load-bearing bone with mechanical stability,
      allowing for earlier implant placement in strong bone.

PMID- 12498433
TI  - Ridge-lapping restorative crowns over endosteal and subperiosteal implant
      abutments.
AB  - Crowns on countless dental implant abutments have been successfully ridge lapped
      for over 25 years. When properly fabricated, ease of cleansing and maintenance of
      health at the pergingival site is routine. The advantages of this technique are
      significant. It promotes pleasing aesthetic results almost regardless of the
      vestibulo-lingual and mesio-distal location of the abutment relative to the
      required position of the crown. The technique-sensitive procedures associated
      with the creation and maintenance of acceptable emergent profiles are rendered
      unnecessary. Ridge lapping is compatible with abutment heads of any diameter and
      configuration and with cementable or screw-retained fixed prostheses. This
      article discusses current opinion and controversy regarding ridge lapping of
      crowns over implant abutments and offers step-by-step procedures in the
      diagnosis, design, fabrication, and professional and home care maintenance of
      highly aesthetic ridge-lapped crowns over abutments of the common dental implant
      modalities.

PMID- 12498434
TI  - Use of autogenous bone grafting to reconstruct a mandibular knife edge ridge
      before implant surgery: a case report.
AB  - Patients can present some anatomic limitations that prevent ideal implant
      placement, and it might be necessary to reconstruct the alveolar ridge. Intraoral
      autogenous bone grafts are the ideal source for the reconstruction of small
      deficiencies. Mandibular symphysis or mandibular ramus area (or both) may be used
      for bone harvesting. Use of intraoral sites has many advantages compared with the
      use of extraoral sites.

PMID- 12498435
TI  - Implantologists have rights, too!

PMID- 12498436
TI  - Localized ridge augmentation using titanium micromesh.
AB  - Guided bone regeneration (GBR) has been used recently for the regeneration of
      bone in conjunction with the placement of dental implants, for augmentation of
      resorbed alveolar crests, and to treat localized ridge deformities. Twenty-two
      patients with alveolar crest defects or peri-implant dehiscences participated in
      this study. Titanium implants were inserted, and the defects were covered with a
      titanium micromesh, above which was positioned an e-PTFE membrane. After healing,
      the 2 membranes were removed and a small specimen of the underlying tissues was
      retrieved with a small trephine. The postoperative healing was mostly uneventful,
      and only a few dehiscences with membrane exposure were observed. The space under
      the membranes was, in all patients, filled by a tissue with the macroscopic
      features of newly formed bone. No residual bone defects were observed and an
      increase of the alveolar width or height was observed. No untoward effects on
      bone regeneration were observed in the cases with membrane exposure. Histology
      showed that the underlying regenerated tissues were composed, in all cases, by
      newly formed bone. In conclusion, our results show that very satisfactory results
      concerning GBR techniques can be obtained even without the use of grafts under
      barrier membranes.

PMID- 12498437
TI  - Therapeutic biomechanics concepts and clinical procedures to reduce implant
      loading. Part I.
AB  - A new approach called therapeutic biomechanics that uses 5 possible corrective
      procedures that can be used in conjunction with each other to reduce implant
      loading has been suggested. These procedures are the following: (1) a cross
      occlusion (to reduce horizontal implant offset); (2) the head (hex) of the
      implant should be placed as close to the midline of the restoration as possible;
      (3) angled or custom reangulated abutment; (4) shallow cusp inclines; and (5)
      modified centric occlusal anatomy. On maxillary anterior restorations, a
      horizontal lingual stop redirects the resultant line of force in a vertical
      direction much closer to the implant and supporting bone. Part II of this paper
      will focus on laboratory and clinical procedures to implement the concept of
      therapeutic biomechanics.

PMID- 12498438
TI  - Therapeutic biomechanics concepts and clinical procedures to reduce implant
      loading. Part II: therapeutic differential loading.
AB  - Practical laboratory procedures were suggested in order to provide a modified
      occlusal anatomy to reduce implant loading. The concept of differential mobility
      caused by the flexion between a natural tooth/periodontal ligament interface with
      its supporting bone, compared with the stiffness of the implant/bone interface,
      was described. When individual tooth-supported and implant-supported prostheses
      coexist in the same arch, this differential mobility can shift the loading
      disproportionately from the natural teeth to the implants. A new concept of
      therapeutic differential loading is introduced and a clinical technique of
      differential occlusal adjustment is described to bring about a more favorable
      distribution of loading to all the supporting bone. Long-term natural tooth
      intrusion can cause implant overload. Therefore, it is suggested that periodic
      differential occlusal adjustment procedures be used to re-establish a long-term
      balance of loading between individual implant- and tooth-supported prostheses
      within the same arch.

PMID- 12498439
TI  - Immediate replacement of nonrestorable roots.
AB  - The following paper represents a case report describing procedures and techniques
      that have been successfully performed clinically over a period of 52 months. The
      intent of these procedures is to replace nonrestorable roots in fresh extraction
      sites with immediate fixture placement and provisional prosthesis placement at
      the time of fixture placement.

PMID- 12498440
TI  - An impression technique to accurately transfer soft tissue contours for implant
      supported restorations: three case reports.
AB  - This article describes an alternative method for making an impression of implants
      that will simultaneously capture the soft tissue contours accurately. This
      customizing of the pick-up impression technique is specifically useful for
      aesthetic areas.

PMID- 12498441
TI  - Restoration of divergent free-standing implants in the maxilla.
AB  - Divergent implants in the maxilla can make restoration with removable prosthetics
      difficult when the implants will not be splinted with a superstructure.
      Attachments to be used with individual implants require that the implants be
      within 10 degrees of divergence. This article will address a new angled male
      designed to fit the locator attachment (female component) that can accommodate up
      to a 40 degrees divergence.

PMID- 12498442
TI  - Alternative retention for an implant-retained auricular prosthesis.
AB  - The introduction of intraoral endosseous implants was inevitably followed by
      their external use in maxillofacial prosthodontics. Bar and clip attachments
      provide satisfactory retention for auricular prostheses, although the bar may
      inhibit patient hygiene by limiting access to the defect area. A simple clinical
      and laboratory technique to enhance the retention of an implant-retained
      auricular prosthesis is described, with custom-made stud attachments used for
      retention. Improved access for hygiene is provided. A clinical case is presented.

PMID- 12498443
TI  - A clinical method for the diagnosis and treatment planning of restorative dental
      patients.
AB  - This article describes a method of clinical diagnosis and treatment planning for
      restorative dental patients that emphasizes well-defined pre- and posttreatment
      communication between practitioner and patient.

PMID- 12498444
TI  - Reconstruction of the severely resorbed atrophic edentulous ridge of the maxilla
      and mandible for implant rehabilitation: report of a case.
AB  - We describe a case with a severely resorbed atrophic edentulous ridge in both the
      maxilla and mandible. The maxilla was reconstructed using a sinus-lifting
      procedure and onlay bone graft. The mandible was reconstructed by anterior
      osteotomy with an interpositional sandwich iliac bone graft at the symphysis
      area, subperiosteally with iliac bone chips mixed with hydroxylapatite
      bilaterally at the posterior atrophic ridge, and vestibuloplasty with a split
      thickness skin graft (STSG). After full-mouth implant rehabilitation, a 5-year
      follow-up of this case shows a satisfactory result.

PMID- 12498445
TI  - Report from Israel.

PMID- 12498446
TI  - The evolution of multiplanar diagnostic imaging: predictable transfer of
      preoperative analysis to the surgical site.
AB  - Presurgical planning and communication between the prosthodontist and the surgeon
      is essential to achieve optimal placement of functional implants. Besides the
      basic clinical examination and the use of mounted study casts, radiographic
      imaging is an essential adjunctive aid in treatment planning. In the past decade,
      multiplanar reformatted computerized tomography (CT) has become the most
      comprehensive and accurate aid for implant treatment planning. Available software
      programs allow precise assessment of the 3-dimensional architecture and internal
      anatomy of the jaws. The programs enable accurate preoperative evaluation for
      planning implant placement with a maximum use of bone. However, the accurate
      transfer of the implant analysis from 2- and 3-dimensional computer
      reconstruction to the surgical site was not predictable until recently. As
      advancements occurred in technology with the advent of the helical CT scanner and
      rapid prototype 3-dimensional model production by stereolithography, a CAD-CAM
      program was developed to create an accurate transfer from the image to the
      surgical site. Detailed preoperative analyses of the quantity and quality of bone
      as well as the ideal positioning of implant fixtures may be established with the
      aid of a surgical guide that is placed directly on the bone for precise implant
      insertion.

PMID- 12498447
TI  - Enhancement of osteoblast proliferation in vitro by selective enrichment of
      demineralized freeze-dried bone allograft with specific growth factors.
AB  - Decalcified freeze-dried bone allograft (DFDBA), believed to serve as a matrix
      for new bone growth and to contain various bone-inducing growth factors, is
      currently used to regenerate periodontal defects and to restore and maintain
      dental alveolar ridges. Growth factors within DFDBA are extracted during the
      demineralization process, thus rendering the allograft incapable of spontaneous
      osteogenesis; however, exogenous growth factor addition to DFDBA may enhance the
      osteogenic capacity of native osteoblasts. This study's purpose is to evaluate
      murine osteoblast proliferation in the presence of various exogenous soluble
      growth factors as measured by fluorescence units. Osteoblasts harvested from
      mouse pup calvaria were cultured with 2% residual calcium-DFDBA and supplemented
      by one of the following growth factors or combinations of these factors:
      transforming growth factor-beta (TGF-beta), insulin-like growth factor-I (IGF-I),
      platelet-derived growth factor (PDGF), fibroblast growth factors basic (bFGF), or
      vascular endothelial growth factors (VEGF). Osteoblast proliferation rates
      indicate that the in vitro supplementation of 2% residual calcium-DFDBA with the
      combination of IGF and TGF-beta, IGF and PDGF, and PDGF and TGF-beta
      significantly (P < or = .05) enhance murine osteoblast activity and proliferation
      at 7 days compared with the control containing no exogenous growth factors.

PMID- 12498448
TI  - Relationship between implant preload and screw loosening on implant-supported
      prostheses.
AB  - The purpose of this study was to determine whether varying the preload on the
      implant-abutment complex would affect screw loosening under simulated loading
      conditions. Abutment screws in sample models were tightened to 25, 30, 35, and 40
      N-cm. One group of samples was allowed to stand for 3 hours after being torqued
      and then loosened. Another group of samples was retorqued after 10 minutes with
      the same initial torque value and then allowed to stand for 3 hours before
      loosening. For the load group of samples, the abutments were torqued into place,
      retorqued after 10 minutes, and a load applied for 3 hours before loosening.
      Cyclic loading was carried out using a servo-hydraulic testing machine with the
      values cycled between 1 and 26 pounds and the load applied directly to the
      abutments. Analysis of variance, analysis of covariance, and linear regression
      analysis was performed. Within the parameters of this in vitro investigation, the
      following recommendations can be made: (1) retightening abutment screws 10
      minutes after the initial torque applications should be routinely performed and
      (2) increasing the torque value for abutment screws above 30 N-cm can be
      beneficial for abutment-implant stability and to decrease screw loosening.

PMID- 12498449
TI  - Risk factors affecting dental implant survival.
AB  - Given the predictability of dental implant success, the attention of the
      scientific community is moving from descriptions of implant success toward a more
      detailed analysis of factors associated with implant failure. The purposes of
      this study were (1) to estimate the 1- and 5-year survival of Bicon dental
      implants and (2) to identify risk factors associated with implant failure in an
      objective, statistically valid manner. To address the research purposes, we used
      a retrospective cohort study design and a study sample composed of patients who
      had one or more implants placed. The predictor variables were grouped into the
      following categories: demographic, health status, anatomic, implant fixture
      specific, prosthetic, perioperative, and ancillary variables. The major outcome
      variable of interest was implant failure defined as implant removal. Overall
      implant survival was estimated using the Kaplan-Meier analysis. Risk factors for
      implant failure were identified using the Cox proportional hazard regression
      models. The study sample was composed of 677 patients who had 677 implants
      randomly selected for analysis. The overall 1- and 5-year survival of the Bicon
      implant system was 95.2% and 90.2%, respectively. After adjusting for other
      covariates in a multivariate model, both tobacco use (P = .0004) and single-stage
      implant placement (P = .01) were statistically associated with an increased risk
      for failure. The results of these analyses suggest that the overall survival of
      the Bicon dental implant is comparable with other current implant systems. In
      addition, after controlling for covariates, we identified 2 exposures associated
      with implant survival, tobacco use and implant staging. Of interest, both of
      these exposures are under the clinician's control.

PMID- 12498450
TI  - An overview of the O-ring implant overdenture attachment: clinical reports.
AB  - The O-ring is used to increase retention of implant complete and partial
      overdenture prostheses. They possess a number of advantages, including ease of
      use and maintenance, low cost, and possible elimination of a superstructure bar.
      O-rings wear over time, gradually lose retention, and must be replaced
      periodically. It is essential that O-ring abutments be parallel to each other.
      Two cases are presented showing the use of O-rings with a complete mandibular
      implant overdenture and a maxillary removable partial denture.

PMID- 12498451
TI  - Immediate implant loading: a case report.
AB  - The therapeutic goal of implant dentistry is not merely tooth replacement but
      total oral rehabilitation. Considering dental implants as a treatment option can
      provide patients with positive, long-term results. Implants have developed into a
      viable alternative to conventional prosthetic reconstruction of edentulous areas.
      They provide excellent support for fixed or fixed detachable appliances, which
      increases function compared with conventional complete dentures. Implant
      dentistry has gone through many phases over the years. Modern technology and
      design allows us to predictably place our dental implants in immediate extraction
      sites and often load the implants at the time of placement. Single tooth-by-tooth
      reconstruction provides easy access for the patient to floss and clean the areas
      compared with the relative difficulty in maintenance when crowns are splinted.
      This case study demonstrates full maxillary and partial mandibular reconstruction
      using dental implants. The implants were surgically placed immediately after
      extractions and loaded using a stable roundhouse composite temporary bridge.
      Following osseointegration, the implants were permanently restored with
      individual crowns.

PMID- 12498452
TI  - Apical (retrograde) peri-implantitis: a case report of an active lesion.

PMID- 12498453
TI  - US Supreme Court decisions, expert testimony, and implant dentistry.
AB  - There have been 3 US Supreme Court decisions in the last 8 years that have
      established new rules of admissibility of expert witness testimony. These will
      have great bearing on the practice of oral implantology now and in the future.

PMID- 12498454
TI  - Guidelines for expert testimony in implant dentistry.

PMID- 12498455
TI  - The 50th anniversary meeting of the American Academy of Implant Dentistry.

PMID- 12498456
TI  - Bone response to machined and resorbable blast material titanium implants: an
      experimental study in rabbits.
AB  - The aim of the present study was a comparison of implants' responses to a
      machined surface and to a surface sandblasted with hydroxyapatite (HA) particles
      (resorbable blast material [RBM]). Threaded machined and RBM, grade 3,
      commercially pure, titanium, screw-shaped inplants were used in this study.
      Twenty-four New Zealand white mature male rabbits were used. The inplants were
      inserted into the articular femoral knee joint according to a previously
      described technique. Each rabbit received 2 inplants, 1 test (RBM) and 1 control
      (machined). A total of 48 implants (24 control and 24 test) were inserted. The
      rabbits were anesthetized with intramuscular injections of fluanisone (0.7 mg/ kg
      body weight) and diazepam (1.5 mg/kg b.wt.), and local anesthesia was given using
      1 mL of 2% lidocaine/adrenalin solution. Two rabbits died in the postoperative
      course. Four animals were euthanatized with an overdose of intravenous
      pentobarbital after 1, 2, 3, and 4 weeks; 6 rabbits were euthanatized after 8
      weeks. A total of 44 implants were retrieved. The specimens were processed with
      the Precise 1 Automated System to obtain thin ground sections. A total of 3
      slides were obtained for each implant. The slides were stained with acid and
      basic fuchsin and toluidine blue. The slides were observed in normal transmitted
      light under a Leitz Laborlux microscope, and histomorphometric analysis was
      performed. With the machined implants, it was possible to observe the presence of
      bone trabeculae near the implant surface at low magnification. At higher
      magnification many actively secreting alkaline phosphatasepositive (ALP+)
      osteoblasts were observed. In many areas, a not yet mineralized matrix was
      present. After 4 to 8 weeks, mature bone appeared in direct contact with the
      implant surface, but in many areas a not yet mineralized osteoid matrix was
      interposed between the mineralized bone and implant surface. In the RBM implants,
      many ALP+ osteoblasts were present and in direct contact with the implant
      surface. In other areas of the implant perimeter it was possible to observe the
      formation of an osteoid matrix directly on the implant surface. Mature bone with
      few marrow spaces was present after 4 to 8 weeks. Beginning in the third week, a
      statistically significant difference (P < .001) was found in the bone-implant
      contact percentages in machined and RBM implants. It must be stressed that these
      results have been obtained in a passive, nonloaded situation.

PMID- 12498457
TI  - Clinical radiographic, and histologic evaluation of maxillary bone reconstruction
      by using a titanium mesh and autogenous iliac graft: a case report.
AB  - The current clinical report describes the use of titanium mesh for maxillary
      alveolar ridge augmentation. Autogenous bone graft was harvested from the iliac
      crest and was loaded on a titanium mesh that was left in the patient's maxilla
      for 7 months before it was removed. Twelve months after the bone grafting
      procedure the patient received 10 implants on the maxilla, and a biopsy was taken
      from the augmented ridge. CT scan examination was performed before and after the
      maxillary ridge augmentation. Clinical evaluation revealed successful integration
      of the graft. The radiographic analysis demonstrated that a 10-mm vertical ridge
      augmentation had been achieved. Histologic evaluation revealed remnants of the
      autogenous bone graft still present, whereas the grafted area had a reduced
      remodeling activity. The clinical report demonstrated the potential of the
      titanium mesh to achieve extensive alveolar ridge augmentation, whereas the
      augmented ridge may possess an inferior capability forbone remodeling.

PMID- 12498458
TI  - Treatment planning to retain hopeless teeth as support for transitional
      appliances: three case reports.
AB  - Treatment in endosteal implant dentistry follows an orderly sequence. Determining
      a patient's need and desire, removal of hopeless teeth, bone augmentation (if
      necessary), implant placement, implant uncovery, and prosthetic restoration are
      considered in order. Three case reports that alter traditional treatment planning
      sequence are presented. Possible potential benefits and disadvantages to
      practitioners and patients are discussed.

PMID- 12498459
TI  - Osseous regeneration in compromised extraction sites: a ten-year case study.
AB  - One of the many problems facing surgeons is finding adequate bone sites for
      implant support. Without adequate bone, there can be implant failure or poor
      esthetic results. By using guided tissue regeneration (GTR) membranes and bone
      grafting materials, implants may be placed into immediate extraction sites and
      areas with large osseous defects with an expectation of long-term positive
      results. These concepts are illustrated by comparing the results of a ten-year
      follow-up evaluation of a patient lacking healthy bone at the implant site with
      another case in which the implant site had bone of acceptable morphology and
      density, with both cases showing similarly good results.

PMID- 12498460
TI  - An incision design to promote a gingival base for the creation of interdental
      implant papillae.
AB  - A surgical flap method that promotes reproduction of the interdental papilla for
      endosseous dental implant treatment is described. This incision design allows
      lifting of the gingiva without disrupting the periosteum and its blood supply.

PMID- 12498461
TI  - The use of computerized tomography for diagnosis and treatment planning in
      implant dentistry.
AB  - Preoperative radiographic imaging of recipient sites for implant placement is
      imperative to obtain a functional and aesthetic implant-supported prosthesis.
      Although conventional radiographic techniques have inherent problems that
      restrict accurate imaging, the main drawback of panoramic and periapical
      radiography is the two-dimensional image. Computerized tomography provides cross
      sectional radiographic images that facilitate proper assessment of potential
      recipient sites for implant placement. This paper reviews the role of
      computerized tomography in implant dentistry.

PMID- 12498462
TI  - If it ain't broke..

PMID- 12498463
TI  - A synthetic bioactive resorbable graft for predictable implant reconstruction:
      part one.
AB  - Animal studies were conducted to evaluate the cell response and chemical
      potentiality of a synthetic bioactive resorbable graft (SBRG) made of nonceramic
      cluster particulate of low-temperature HA material. The study evaluated bone
      bridging of the SBRG particulates in 1-mm wide implant channels of 5 x 8 mm long
      roughened titanium interface in 6 dogs and compared results to the same implant
      channels left empty as controls at 6- and 12-week intervals. Resorption rate
      capacity and cell response were evaluated with an assessment of the chemical
      characterization of the synthetic nonceramic material next to the titanium
      implant interfaces. Results of the animal studies were compared with human
      histologic biopsies of the SBRG for bone quality, density, and bone growth into
      defect sites concurrent with resorption time of the graft. One human biopsy
      consisted of a graft mixture of the SBRG and dense bovine-derived HA, compared
      under the electron microscope, including histology by H and E staining. Part 1 of
      this paper presents evidence of the predictability and efficacy of the SBRG
      osteoconductive, particulate chemical potentiality to aid in the regeneration of
      lost bone anatomy next to titanium implant interfaces. Recent technological
      innovations in computer hardware and software have given clinicians the tools to
      determine 3-dimensional quality and density of bone, including anatomical
      discrepancies, which can aid in the diagnosis and treatment planning for grafting
      procedures. When teeth are extracted, the surrounding bone and soft tissue are
      challenged as a result of the natural resorptive process. The diminished
      structural foundation for prosthetic reconstruction, with or without implants,
      can be compromised. A synthetic bioactive resorbable graft material having
      osteoconductive biochemical and biomechanical qualities similar to the host bone
      provides the means to improve compromised bone topography for ridge preservation,
      ridge augmentation, or to enhance the bony site for implant placement and
      subsequent prosthetic rehabilitation. Part two of this paper will demonstrate
      clinical applications of the SBRG material for purposes of implant placement and
      prosthetic reconstruction.

PMID- 12498464
TI  - Predictable synthetic bone grafting procedures for implant reconstruction: part
      two.
AB  - When teeth are missing, the surrounding bone and soft tissue is challenged as a
      result of the natural resorptive process or from traumatic destruction subsequent
      to extraction. The diminished structural foundation for prosthetic reconstruction
      with or without implants can therefore be compromised. Recent technological
      innovations in computer hardware and software have given clinicians the tools to
      determine 3-dimensional anatomy, quality, and density of bone, which can aid in
      the diagnosis and treatment planning for reparative or augmentative grafting
      procedures. Advanced synthetic bioactive resorbable bone graft (SBRG) materials
      and innovative surgical techniques have made it possible to predictably alter the
      defective site to create favorable osseous conditions for implant placement. The
      synthetically derived, resorbable, cluster-like, hydrophilic, particulate, bone
      grafting material, having similar mechanical and chemical properties as the host
      bone, can provide the means to modify existing bone topography by aggressively
      overpacking the material for ridge preservation, ridge augmentation, or to
      enhance the bony site and subsequent prosthetic rehabilitation. Since bone does
      not bridge in empty spaces, the aggressive overfill, commonly referred to as
      force mineralization, controls excessive bleeding and eliminates voids. Part 1 of
      this 2-part series presented evidence of safety and effectiveness of the SBRG
      materials, crystal morphology, chemical properties, and characterization through
      animal and clinical studies. The osteoconductive cluster particulate assists in
      the bridging of lost bone anatomy by chemotactic response and resorption
      concurrent with regeneration of new bone formations. Part 2 demonstrates specific
      clinical handling characteristics and use of this material to facilitate implant
      placement and/or prosthetic reconstruction through clinical case applications.
      Additionally, in a unique clinical presentation, a composite graft mixture
      consisting of the SBRG and dense, ceramic, bovine-derived HA (sintered at 1,150
      degrees C) was compared using electron microscopy.

PMID- 12498465
TI  - Use of an extraoral verification template for dental implant-supported
      prostheses.
AB  - This article demonstrates the utilization of a preprosthetic extraoral
      verification template that could be used to ensure the accuracy of the master
      cast from which the laboratory working model is used as the in vitro foundation
      for the implant-supported prosthesis framework construction.

PMID- 12498466
TI  - Delayed immediate single-step maxillary sinus lift using autologous fibrin
      adhesive in less than 4-millimeter residual alveolar bone: a case report.
AB  - This paper presents a combination of techniques to replace a missing first
      premolar in an atrophic posterior maxillary ridge with less than 4 mm of residual
      bone. Simultaneous sinus lift and implant placement were carried out as a delayed
      immediate procedure 6 weeks following the extraction of the premolar. The
      osteotome technique was used to gain primary stability. Demineralized freeze
      dried bone and deproteinized cancellous bovine bone (Bio-Oss) were used to create
      the bone volume. Autologous fibrin adhesive was subsequently used to stabilize
      the bone grafting materials both in the sinus and on the coronal part of the
      implant. This combined technique preserves the alveolar bone after extraction;
      simplifies the primary closure; avoids a second surgical site; and reduces the
      total operation time, cost, and inconvenience to the patient.

PMID- 12498467
TI  - Transpositioned flap vestibuloplasty combined with implant surgery in the
      severely resorbed atrophic edentulous ridge.
AB  - The use of transpositioned flap (lipswitch) vestibuloplasty combined with implant
      surgery in patients with severely resorbed atrophic edentulous ridges is
      reviewed. The cases of 17 patients with severely resorbed atrophic edentulous
      ridges at the mandible undergoing implant rehabilitation were reviewed. Lipswitch
      vestibuloplasty was followed immediately by the implant surgery. Postoperative
      follow-up consisted of clinical and radiographic examinations. Seventeen patients
      with atrophic ridges (12 class II and 5 class III) each had 2 implant fixtures
      placed in the mandible as abutments for a clip and bar overdenture. The average
      time of follow-up was 6 years. Before surgery, all patients had severely atrophic
      ridges with a compromised shallow vestibule of varying degrees. Satisfactory
      results were observed in regard to the immediate and long-term morphology of the
      vestibule, the health of the peri-implant tissue, the stability of implant
      fixtures, and the functionality of the prostheses. The lipswitch vestibuloplasty
      offers a safe and convenient method of surgical access for implant fixture
      installation, with the advantage of rebuilding the vestibule of a compromised
      atrophic ridge in the anterior mandible.

PMID- 12498469
TI  - In support of the implantologist.

PMID- 12498468
TI  - Immediate loading implants: a clinical report of 1301 implants.
AB  - The purpose of this study is to suggest 4 immediate load of implants techniques
      that are alternative and/or complementary to the traditional submersion
      technique. These techniques meet the criteria for implant immobilization during
      the entire period of osteointegration, and are based on the principles of
      splinting and load sharing. One hundred fifty-three maxillary and 309 mandibular
      arches were treated with 1301 implants. Only implants that satisfied the primary
      retention were immediately loaded with a provisional crown with wings (94),
      provisional plastic prosthesis (478), provisional plastic prosthesis with metal
      frame (293), and intraoral welding (436). Facies morphology, type of occlusion,
      size and function of the tongue, bone density, number, and length of implants
      appeared to have an influence on the results. Success rates achieved over 21
      years are 99.3% with the intraoral welding machine, 98.3% with the provisional
      plastic prosthesis with metal frame, 97.9% with metal wings, and 88.02% with
      provisional plastic prosthesis. This last percentage is reflective of the years
      1974 to 1984 when only blade-forms and root-forms with unscrewable abutments were
      available and a provisional plastic prosthesis was the only immobilization
      technique known. Guidelines are proposed for a treatment plan indicating when and
      why immediate loading implants can be suggested.

PMID- 12498470
TI  - Collagen as an implantable material in medicine and dentistry.
AB  - Collagen is a highly versatile material, extensively used in the medical, dental,
      and pharmacological fields. Collagen is capable of being prepared into cross
      linked compacted solids or into lattice-like gels. Resorbable forms of collagen
      have been used to dress oral wounds, for closure of graft and extraction sites,
      and to promote healing. Collagen-based membranes also have been used in
      periodontal and implant therapy as barriers to prevent epithelial migration and
      allow cells with regenerative capacity to repopulate the defect area. It has been
      hypothesized that membrane regenerative techniques facilitate the natural
      biological potential by creating a favorable environment for periodontal and peri
      implant regeneration. Due to the enormous potential of collagen-based
      regenerative barriers, clinicians may benefit from a review of potential
      applications of implantable collagen and knowledge of collagen preparation and
      membrane types as well as from as awareness of the functional and degradation
      properties of those materials.

PMID- 12498471
TI  - Implant site development and alveolar bone resorption patterns.
AB  - Resorption of the alveolar ridges after tooth extraction can mandate site
      development (preparation) by augmentation, grafting, or both before implants can
      be placed. The fabrication of successful implant prostheses generally can be
      accomplished only if the artificial teeth are placed in the same position as was
      occupied by the natural teeth they are replacing. A knowledge of resorption
      patterns is necessary for satisfactory implant placement.

PMID- 12498472
TI  - Implant surgery: the management of soft tissues.
AB  - Soft tissue healing plays a significant role in determining the outcome of
      implant and other osseous surgery. A variety of methods is required to accomplish
      primary soft tissue closure. These include the techniques of undermining; free
      grafting, both full and split thickness; and pedicle grafting. Preprosthetic
      surgery, which includes the correction of high muscle attachments and vestibular
      deficiencies, involves the use of broad spectrum grafting modalities in order to
      create an appropriate environment for the placement of implants.

PMID- 12498473
TI  - The masticatory efficiency of mandibular implant-supported overdentures as
      compared with tooth-supported overdentures and complete dentures.
AB  - This study assesses the comparative masticatory efficiency (CME) of mandibular
      implant-supported overdentures (ISOs) to tooth-supported overdentures (TSOs) and
      complete dentures (CDs). Three groups of patients in equal numbers were evaluated
      by assessing chewing efficiency, and the results were correlated with tracings of
      mandibular excursion (ME) and electromyographic (EMG) computerized analysis. CME
      was measured by utilizing standardized portions of 2 food staples with fixed
      masticatory sequencing. In a following session, utilizing the same fixed
      masticatory sequence, tracings of ME and EMG of the masseter and temporal muscles
      were recorded and analyzed. The results revealed that the ISO provided the
      greatest degree of efficiency, followed by the TSO and then the CD group. CME is
      more correlated to ME and less correlated to EMG.

PMID- 12498474
TI  - Implant prosthodontics: from single tooth to complex cases.
AB  - Types of commonly used implant prostheses have been described and illustrated,
      including single tooth replacements, multiple tooth replacement fixed prostheses,
      implant and soft-tissue-supported removable complete dentures, implant-supported
      removable complete dentures, and fixed-detachable complete dentures.

PMID- 12498475
TI  - Evaluation of commercial compost quality.
AB  - Ten commercial composts were evaluated on the basis of chemical, physical and
      biological characteristics and compared with a compost produced by a safe matrix
      in controlled conditions. FT-IR spectra, (13)C CP-MAS NMR spectra and molecular
      weights were also assayed on humic acids extracted from the composts. The results
      show that the origin of the starting materials affects the quality of the end
      products especially for their heavy metal content and genotoxic effect. The
      presence of a high percentage of low molecular weight fractions generally
      recorded in the humic acids from commercial composts could be due to uncorrected
      composting process. FT-IR and (13)C CP-MAS NMR spectra agree with functional
      group assignments, characterising the level of humification. The results show
      that commercial composts can display harmful properties probably due to the
      origin of the starting material, therefore a regulation about both compost
      production and characterisation should be suitable.

PMID- 12498476
TI  - A model for the reallocation of recycling containers: application to the case of
      glass.
AB  - From both the social as well as the economic perspective, the recycling of
      household waste products is of growing importance. The recycling of glass in
      particular is one of the most successful as far as public collaboration is
      concerned, as well as due to the demand for recycled material on the part of
      glass manufacturers. This article presents a model for designing the first stage
      in the reverse logistics chain, i.e. the collection of material (in our case,
      applying the model to the collection of glass) directly from the consumer by
      means of containers. The aim of this model is to determine how to distribute the
      recycling containers in a specific region in the most efficient way possible,
      taking into account the economic and sociological characteristics of the
      population (level of education, number of catering establishments, etc.), while
      attempting to maximise the material collected and reducing the logistics costs.
      The model has been applied to the case of the Principality of Asturias, Spain,
      obtaining estimations that improve the performance of the system.

PMID- 12498477
TI  - Adding crumb rubber into exterior wall materials.
AB  - In Arizona US, most houses are built with walls covered by
      stuccos/coatings/mortars. This paper presents an explorative investigation of
      adding crumb rubber into stuccos/coatings/mortars. A series of experiments are
      conducted to examine the thermal and mechanical performance of the crumb rubber
      mixes. The results show that, the mixes with crumb rubber do exhibit more
      desirable performances like being high in crack-resistance and thermal
      insulation, and low in thermal expansion/contraction. The drawback for the crumb
      rubber mixes is the reduction in compressive strength, but which can be
      compensated by other means. As a site experiment, an area of 100 square-feet of
      crumb rubber coatings for two mix designs is sprayed on a tire-adobe wall. After
      being sprayed more than 14 months, the coatings apparently are in good condition.
      Significance of this study is that this practice, if accepted, will yield
      improved products that consume large quantities of crumb rubber.

PMID- 12498478
TI  - Minimisation and utilisation of waste mineral sludge from sodium perborate
      production.
AB  - Various approaches to waste minimisation, waste treatment and recycling or safe
      disposal of the waste mineral sludge from sodium perborate production are
      presented and critically discussed. Some most promising actions for waste (or its
      harmful potential) reduction on the production level are identified. These
      include: a) use of better raw materials (richer boron ore), b) improvement of the
      ore leaching process, and c) intensification of sludge washing and dewatering.
      These source reduction measures have already resulted in 50% reduction of boron
      content in the sludge. Utilisation of the raw or treated (e.g. dried, compacted)
      waste sludge could be found in agriculture, civil engineering and construction
      material production. Agricultural use (as a lime substitute) is based on
      favourable content of calcium-magnesium minerals and alkali pH value of the
      sludge, and simultaneous absence of heavy metals. Application in civil
      engineering (as an aggregate) is possible after calcination, which is costly, or
      as a cement kiln additive. Stabilisation of sludge before disposal, when no
      utilisation is available, is possible by small addition of commercial binders
      (e.g. Portland cement) or larger amounts of pozzolanic wastes (e.g. coal fly
      ash).

PMID- 12498479
TI  - Methane and leachate pollutant emission potential from various fractions of
      municipal solid waste (MSW): effects of source separation and aerobic treatment.
AB  - The effects of source-separation of putrescibles as well as aerobic pre-treatment
      and landfill aeration on the pollutant emission potential of methane and leachate
      pollutants were studied in the fresh (PFMSW) and composted (CPFMSW) source
      separated putrescible fraction of municipal solid waste, and in the grey waste,
      and in lysimeter landfilled grey waste and ten-year-old unsorted MSW from our
      landfill lysimeter study. After 0, 23 and 51 days, an aerobic lysimeter
      experiment, an elution test and biochemical methane potential (BMP) test was done
      on samples. PFMSW had high methane (CH4) potential (410 m(3) CH4 t(-1)TS) as well
      as a high amount of ammonium-nitrogen (3.6 kg NH4-N) was eluted, whereas CPFMSW
      produced 41 m(3) CH4 t(-1)TS and 2.0 kg NH4-N t(-1)TS. A high nitrogen elution
      potential was found in the grey waste (2.1 kg NH4-N t(-1)TS). Aeration for 51
      days in lysimeters reduced CH4 potential by more than 68% for the PFMSW and
      CPFMSW samples, whereas for the lysimeter landfilled grey waste the reduction was
      50% indicating the potential of aeration for CH4 emission reduction. The
      effective separation and biological treatment of the PFMSW are important in
      reducing the environmental impacts of waste management, especially for minimising
      the methane potential of MSW fractions.

PMID- 12498480
TI  - The effect of various environmental and design parameters on methane oxidation in
      a model biofilter.
AB  - Methane from landfills built with RCRA (Resource Conservation and Recovery Act)
      covers is frequently vented directly to the atmosphere. Alternatively, landfill
      gasses could be vented through a layer of soil that could serve as a biofilter to
      oxidize CH4 to carbon dioxide and water. Properly designed soil biofilters may
      reduce atmospheric CH4 emissions from landfills and help reduce the accumulation
      of greenhouse gasses in the atmosphere. This study was conducted to investigate
      the performance of a lab-scale model biofilter system using soil as the filterbed
      medium in packed columns to measure the effect of a variety of environmental and
      design factors on the CH4 oxidation capacity of a soil biofilter. Biofilter
      performance was tested under a variety of environmental and design conditions.
      The optimum soil moisture content for CH4 oxidation in a loamy sand was 13% by
      weight. Addition of NO3-N did not affect the CH4 oxidation rate. Soil depths of
      30 cm and 60 cm were equally efficient in CH4 oxidation. When the CH4 loading
      rate was decreased, the percentage of CH4 oxidized increased. The maximum CH4
      oxidation rate was 27.2 mol m(-2) d(-1) under optimum conditions.

PMID- 12498481
TI  - Linking landfill hydrology and leachate chemical composition at a controlled
      municipal landfill (Kastrup, Denmark) using state-space analysis.
AB  - Leachate production and composition data for a municipal landfill measured over a
      25-year period was used to investigate important processes and parameters. Long
      term leachate production could be satisfactorily predicted from a simple top
      layer landfill hydrology model while short-term predictions were less accurate,
      likely due to water storage in the waste. State-space and multiple regression
      modelling were used to identify relations between different parameters. State
      space models proved most accurate in fitting measured data, likely because
      temporal correlation between measurements is accounted for unlike multiple
      regression. State-space modelling showed that temporal correlation in leachate
      production must be taken into account and confirmed that water storage inside the
      landfill is important. Temporal correlation is also important when predicting pH
      and chloride concentrations but less so for BOD5 and NH3/NH4+concentrations.
      Leachate flow did in general not have a strong impact upon leachate composition,
      small effects were observed for Cl-, and NH3/NH4+ concentrations. It was also
      observed that the mass load of nitrogen from the landfill was strongly dependent
      upon leachate nitrogen (ammonia/ammonium) concentrations and to a lesser degree
      upon leachate flow rates. This study introduces state-space modelling in solid
      waste management as a powerful tool to identify governing parameters for
      hydrological and bio-chemical processes.

PMID- 12498482
TI  - A review of the UK metals recycling industry.
AB  - This paper reviews the volatile nature of the price of recycled metals over the
      past decade and examines legislative and fiscal drivers that have affected the
      industry. Results from this study have shown that the UK scrap metals markets are
      presently seeing some of the lowest scrap prices for nearly a decade for both
      ferrous and non-ferrous metals, in many cases halving in value in less than a
      year. Scrap metals and other recycled materials prices were high in 1994-96,
      which have since fallen back to more traditional low levels. World recessions and
      the steady decline of the UK manufacturing and engineering sectors have effected
      prices. With tougher new Government legislation, such as the Climate Change Levy
      and the proposed End of Life Vehicles Directive, small and medium sized scrap
      merchants are finding it increasingly difficult to compete.

PMID- 12498483
TI  - Calcium hypochlorite removal of mercury and petroleum hydrocarbons from co
      contaminated soils.
AB  - Former oil and gas processing sites are often contaminated with both mercury and
      petroleum hydrocarbons. Traditional methods for treating these co-contaminated
      soils include thermal treatments and placement in landfills (Stepan et al. 1993).
      This study examines a chemical oxidation treatment, calcium hypochlorite, and its
      effectiveness in reducing both the petroleum and mercury content of several
      industrial soils. A sequential extraction method was used to determine the forms
      of mercury removed through the hypochlorite treatment. The forms included five
      organic forms of mercury, mercury associated with the mineral phase, ion
      exchangeable mercury, water phase mercury, and mercury associated with the
      petroleum hydrocarbons. The hypochlorite treatment did lower the mercury content
      of all five soils, but failed to remove the petroleum hydrocarbons from the
      soils. Prior to the hypochlorite treatment the dominant form of mercury was that
      associated with soil organic matter while after treatment most of the mercury
      remaining in the soil was associated with either the petroleum hydrocarbons or
      the mineral phase.

PMID- 12498484
TI  - Report: operational experiences and legal aspects of co-combustion in Germany.
AB  - From 2000-2001, a project entitled "Analysis of effects on environment from waste
      incineration in industrial facilities" was undertaken by Prognos AG. The project
      was funded by the German Environmental Agency and the North Rhine-Westphalian
      Ministry for Environment and Conservation, Agriculture and Consumer Protection.
      This paper presents a summary of the main results. The most important industrial
      processes with practised waste-to-energy are identified, respectively cement
      kilns, steel works, installations in the non ferrous industry and large
      combustion plants. The amount of waste being co-incinerated is determined in
      permitting procedures. In general the volume of permitted and practised co
      incineration is increasing in Germany. For the greatest possible use of waste it
      is necessary to establish suitable measures to prevent or to limit, as far as
      possible, environmental pollution. Emission limit values are determined according
      to the requirements set out in the German Standards, 17th BImSchV and TA Luft.
      Plant operators meet generally the air emission limit values fixed in the
      respective granted permits.

PMID- 12498485
TI  - Should we measure cerebral blood flow in head-injured patients?
AB  - Inadequate cerebral blood flow (CBF) after head injury is an important cause of
      secondary ischaemic damage. Rapid identification of episodes of hypo- or
      hyperperfusion would allow timely intervention and would possibly improve
      outcome. Despite a large number of methods to estimate CBF, this concept is only
      marginally implemented in clinical practice. The methods to detect such episodes
      are limited for technical reasons, but also because the thresholds of ischaemia
      and hyperaemia are variable after head injury. Furthermore, we are not always
      able to manipulate CBF in a controlled manner. Accordingly, it is not surprising
      that attempts to compare a CBF-targeted strategy with another management option
      have failed to demonstrate a clear benefit. Methods need to be developed that
      allow either identification of thresholds for critically low or high CBF in
      individual patients, allow monitoring oxygen extraction fraction, representing
      circulatory reserve, or alternatively provide a measure of the volume of
      ischaemic or hyperaemic brain.

PMID- 12498486
TI  - Team working: a report from the Society of British Neurological Surgeons.
AB  - Despite the obvious advantages of team-working these early pilot studies have
      provided an opportunity to see how difficult it is to formalize this concept in
      the current neurosurgical environment. The team approach and the patient database
      have often demonstrated the problems of patient management due to lack of
      resources, insufficient staff and pressure to deliver volume, rather than quality
      with inadequate levels of staff--precisely the criticism levelled at Bristol. If
      team working in neurosurgery is to succeed in developing quality standards for
      the continuity of patient care then the infrastructure has to be developed,
      support guaranteed and some aspects of culture within the service changed.

PMID- 12498487
TI  - The operative learning curve for vestibular schwannoma excision via the
      retrosigmoid approach.
AB  - The results of 127 operations for vestibular schwannomata via the retrosigmoid
      approach performed by a single surgeon over a 24-year period are examined. Facial
      nerve preservation and function, morbidity and mortality were recorded
      prospectively for three consecutive 8-year periods to assess the effect of
      increasing surgical experience on outcome. Rates of facial nerve preservation and
      good function (House grade I & II) improved over the study period. This reached
      statistical significance for medium-sized tumours, indicating that the effect was
      independent of tumour size, whose distribution varied through the series.
      Improvements occurred independently in the ability to preserve the nerve and its
      function. Analysis of the percentage of good facial nerve outcomes achieved over
      time indicated that the improvements occurred mainly between the 40th and 100th
      cases. Overall mortality was 3% and there were no deaths in the final time
      period. The implications of these findings for patient care and surgical training
      are discussed.

PMID- 12498488
TI  - Driving after epilepsy surgery: effects of visual field defects and epilepsy
      control.
AB  - The aim of this study was to assess the eligibility to drive in patients with
      mesial temporal sclerosis who undergo anterior temporal lobectomy. The two major
      determinants in a patient's ability to drive after such surgery are visual field
      defects and their seizure frequency. Thirteen patients were selected. The
      postoperative seizure frequency was assessed using Engel's criteria. Automated
      static perimetry was performed which consisted of a Humphrey Field Analyser (HFA)
      30-2 Test, one for each eye and a Binocular Esterman 120 Test. Seven out of the
      13 (54%) selected patients had no seizures post-operatively (Engel's 1); three
      (23%) patients had less than two seizures per year (Engel's 2) and three (23%)
      had more than 90% improvement in the frequency of seizures (Engel's 3). The seven
      patients with no seizures postoperatively were eligible to apply for a driving
      licence. Automated static perimetry performed on the same patients revealed three
      (23%) had normal visual field or non-specific loss, seven (54%) had partial
      homonymous quadrantanopia, one (8%) had complete homonymous quadrantanopia and
      two (15%) had bilateral concentric loss attributable to vigabatrin, which may
      have masked any loss occurring due to surgery. Of the 13 patients, only seven
      (54%) passed the standardised DVLA Esterman visual field test. Of the six (46%)
      who failed DVLA Esterman visual field test, one had complete homonymous
      quadrantanopia, three had incomplete homonymous quadrantanopia and two had
      concentric loss (due to vigabatrin). Although seven (54%) patients passed the
      visual field test and seven (54%) patients were seizure free only five of the
      seven seizure-free patients (i.e. 38% of the total number of patients) had visual
      fields that would make them eligible to drive. As driving is now stated by
      patients' as a major factor that improves their quality of life, it is important
      to stress the significance of surgically induced or other iatrogenic visual field
      defects that may prevent them from driving prior to the operation to avoid
      disappointments afterwards.

PMID- 12498489
TI  - Neuropathological diagnostic accuracy.
AB  - This study investigated variations in neuropathological diagnosis when
      histopathological slides are evaluated with access to all information pertinent
      to a case, compared with evaluation of H & E stained slides with only limited
      clinical information. The aim of the study is to evaluate the role of 'local'
      factors in reaching a definitive, neuropathological diagnosis. Each of 227 cases
      was reviewed by the local neuropathologist at one of three European centres with
      access to all clinical, radiological and histopathological data. Each case was
      also reviewed by a second, independent neuropathologist at another European unit,
      who was blinded to the local pathologist's diagnosis, and only had access to the
      age and sex of the patient and the location of the lesion. For the
      histopathological evaluation, initially he had access to H & E and GFAP stains
      only. Diagnoses were made using the WHO 2000 classification system and the two
      evaluations were classified into one of the following four categories: complete
      agreement; minor disagreement (not affecting treatment); minor disagreement
      (affecting treatment); complete disagreement. In 175 (77.1%) cases there was
      complete agreement between the two neuropathologists and in 18 (7.9%) cases there
      were non-treatment altering discrepancies in the diagnoses. Overall, there was
      disagreement which might potentially affect treatment in 34 (15%) of the cases.
      Histopathological diagnosis of the majority (85%) of brain tumours is accurate
      and uniform. However, histopathology is subject to a degree of interpretation.
      The availability of full, 'local', clinical information may be of considerable
      importance to the diagnostic process.

PMID- 12498490
TI  - The role of neuroendoscopy in the management of brain tumours.
AB  - Neuroendoscopy is increasingly used in the management of brain tumours and tumour
      related hydrocephalus and this study reviews the efficacy of neuroendoscopic
      interventions in this unit in patients with brain tumours. A series of 87
      neuroendoscopic operations carried out in 77 patients with brain tumours over a 6
      year period is reported. The age range of the patients was from 5 months to 70
      years (median 13 years). In 56 cases (64%) presentation was with a newly
      diagnosed tumour and hydrocephalus. The majority of the remaining patients had
      varying degrees of worsening hydrocephalus on the background of a previously
      diagnosed tumour. Neuroendoscopic third ventriculostomy (NTV) was successful in
      relieving hydrocephalus in the short term in 63/66 cases (95%) and in the longer
      term in 55/66 cases (83%). Neuroendoscopic tumour biopsies were successful in
      providing a tissue diagnosis in 17/28 cases (61%) and four extensive and three
      partial resections of tumour were carried out. There were two deaths within 30
      days of the procedure with only one of these, secondary to intraventricular
      haemorrhage, directly related to neuroendoscopy. Few significant complications
      were noted otherwise. For selected intraventricular and paraventricular tumours
      neuroendoscopy offers the opportunity to combine relief of hydrocephalus with
      tumour biopsy and sampling of CSF in a single procedure.

PMID- 12498491
TI  - Discordant temporal patterns of S100beta and cleaved tau protein elevation after
      head injury: a pilot study.
AB  - There is considerable interest in S100beta protein as a potential marker that can
      be used to quantify central nervous system injury. However, increasing
      appreciation that S100beta may be produced by non-neural tissue (specifically
      adipocytes), has led to a search for more specific markers of brain injury.
      Recent interests have focused on a cleaved form of tau protein (c tauP) which is
      elevated in CSF from patients suffering traumatic brain injury. We have
      investigated whether levels in peripheral blood are a satisfactory alternative to
      provide an accessible marker of CNS injury severity. We measured levels of
      S100beta and c tauP in arterial blood from 20 patients with severe head injury.
      When compared with normal values S100beta was elevated 10-fold in the first 24
      hours and c tauP was elevated at all time points, but showed a reversal of the
      temporal trend observed with S100beta. Patients with a poor outcome (GOS 1-3) had
      significantly higher S100beta levels on day one. Plasma c tauP levels did not
      correlate with outcome following head injury.

PMID- 12498492
TI  - Changing utilization of stereotactic radiosurgery in the UK: the Sheffield
      experience.
AB  - Recognizing a change in our workload and variabilities in referral patterns, we
      reviewed our previous activity from 1994 to 2000 retrospectively and examined
      prospectively formal referrals to the Unit in 2001. Arteriovenous malformations
      still constitute 30% of referrals and treatments, although as a proportion of our
      workload, this has declined. Radiosurgery is increasingly being chosen as a first
      line treatment for small and moderate-sized acoustic neuromas, although referral
      rates vary widely, some neuroscience units referring all and others none of their
      acoustic neuromas at least for a radiosurgical opinion. About 100 meningiomas,
      mainly skull-base and/or recurrent tumours after previous surgery, are now
      treated per year. Compared with other units world-wide, very few pituitary
      adenomas and cerebral metastases are treated. The implications of this are
      discussed.

PMID- 12498493
TI  - Craniocervical fusion for rheumatoid arthritis: comparison of sublaminar wires
      and the lateral mass screw craniocervical fusion.
AB  - The majority of rheumatoid arthritis patients with C1/2 instability causing neck
      pain and neurological compromise can be treated with unisegmental fusion.
      However, a minority will require decompression and more extensive craniocervical
      fusion. Two cohorts of patients with rheumatoid arthritis requiring decompression
      and craniocervical fusion were included in a retrospective study comparing
      sublaminar wiring (Ransford Loop, n = 10, follow-up = 36 +/- 9.5 months) and
      lateral mass screws (Cervifix system, n = 11; follow-up = 39.7 +/- 7.9 months).
      Both cohorts of patients experienced significant improvements in high cervical
      pain scores [McGill 5-point score; preop = 4.5 +/- 0.75 for Cervifix and 4.5 +/-
      0.75 for Ransford loop; postop = 1.17 +/- 0.9 (p = 0.003) for Cervifix (at 39.7
      months +/-7.9) and 2.8 +/- 1.6 (p = 0.011) for Ransford loop (at 36 +/- 9.5
      months)]. Lateral mass screws for craniocervical fusion (seven out of 11 pain
      free) appear to produce better early results for rheumatoid arthritis patients
      suffering high cervical neck pain than sublaminar wire techniques (three out of
      10 pain free).

PMID- 12498494
TI  - Prognosis of severe head injury: an experience in Thailand.
AB  - This study of 300 patients with severe head injury evaluated the clinical
      predictors determined after admission and associated with significant increase of
      poor outcome. The overall poor outcome was 58%. Logistic regression showed that
      age, status of basal cisterns on initial CT, Glasgow Coma Scale score (GCS) at 24
      h after injury and electrolyte derangement occurring during admission strongly
      correlated with the outcome. A probability diagram of the outcome determined at
      24 h after injury from the combination of the significant predictive factors
      provides a basis for determining the interventions to the appropriate target
      population. Intracranial pressure monitors with sophisticated devices may not be
      suitable for a developing country. Allocation of resources toward development of
      adequate intensive care beds and well-trained staff combined with serial CT
      imaging may be an alternative approach for the improvement of the outcome of
      severe head injury.

PMID- 12498495
TI  - Laminal fenestration for the treatment of lumbar nerve root foraminal stenosis.
AB  - A new technique is reported for the treatment of isolated lumbar nerve root
      foraminal stenosis. Nerve root decompression is performed via a 5-mm drill hole
      in the lamina immediately below the superior facet. This technique preserves
      spinal stability even if done at multiple levels. It also provides early mobility
      of the patient and subsequently shortens the hospital stay. The technical details
      are described.

PMID- 12498496
TI  - Minimally invasive electrodiagnostic monitoring in epilepsy surgery.
AB  - A new method of obtaining electrographic recordings from endoscopically-based
      intraventricular monitoring was performed in three patients with intractable
      epilepsy, who subsequently underwent open resective neurosurgery. As a minimally
      invasive procedure, it was associated with no peri-operative complications, and
      electrical intraoperative monitoring of the epileptogenic focus yielded excellent
      results.

PMID- 12498497
TI  - Percivall Pott and the miners of Cornwall.
AB  - Percivall Pott (1714-1788) was an astute and prolific mid-eighteenth century
      English surgeon with a strong interest in head injury. He was partial to the use
      of the trephine for all skull fractures and favoured early exploratory
      trephination when an intracranial collection could not be ruled out. If
      haemorrhage or abscess was beneath the dura, it was incised. Later in eighteenth
      century England and France, trephination fell out of favour. This was especially
      so in the crowded hospitals where putrid conditions were common. Surprisingly, on
      the remote southwestern English peninsula of Cornwall, where compound depressed
      skull fractures in miners were a frequent occurrence, Pott's principles prevailed
      unchanged. Generations of surgeons trephined early in suspected cranial
      fractures, without waiting for symptoms of compression or irritation. A large
      percentage of patients recovered. Those who died generally had diffuse injury,
      brain laceration, or a fractured base. The Atlantic breezes were believed
      beneficial to recovery. The operation of early 'preventive' trephination
      continued in the Cornish mining districts through the 1870s, when antiseptic
      methods were gradually adopted as elsewhere in England. Head injuries in miners
      became less common as mining reforms were introduced and head protection
      improved.

PMID- 12498498
TI  - Spontaneous spinal cord herniation.
AB  - Spontaneous spinal cord herniation is a rare and under recognized condition. The
      commonest presentation is a Brown-sequard syndrome. It most commonly occurs in
      the thoracic region through an anterolateral dural defect, and the
      pathophysiology is ill understood. We present a case of spontaneous spinal cord
      herniation along with a review of literature.

PMID- 12498499
TI  - Clear cell sarcoma (malignant melanoma of soft parts) presenting as cervical
      myelopathy.
AB  - A 47-year-old woman presented with a 2 year history of progressive cervical
      myelopathy. MRI revealed a lesion anterior to the cord at the level of C1/C2.
      This was excised and found to be a clear cell sarcoma, a tumour not previously
      reported at this site.

PMID- 12498500
TI  - Paget's disease complicated by hydrocephalus and syringomyelia.
AB  - The authors report a case of Paget's disease involving the skull with the rare
      but severe complications of hydrocephalus and syringomyelia related to basilar
      impression. Complications of Paget's disease of the skull are briefly discussed
      and current treatment strategies outlined.

PMID- 12498501
TI  - Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and
      review of the literature.
AB  - Schilder's myelinoclastic diffuse sclerosis is a rare demyelinating disease,
      which often mimics intracranial neoplasm or abscess. This disease is of
      importance to the neurosurgeon in that the clinical manifestations and course may
      closely simulate brain tumour, including the development of papilloedema and
      other signs of increased intracranial pressure. We have treated a 29-year-old
      right-handed young man presenting with left hemiplegia, aphasia and behavioural
      changes. Magnetic resonance imaging showed two large lesions, irregular contrast
      enhancing, in the subcortical white matter of the right frontal and parietal
      lobes, and increased intracranial pressure. Definitive diagnosis was made with
      biopsy. The characteristic pathological features are demyelinization of the white
      matter, lymphocytic perivascular infiltrates, microglial proliferation and
      immunohistochemical signs. The patient improved with steroid treatment.
      Schilder's disease constitutes an important diagnosis for any neurosurgeon to be
      aware of which has not received adequate coverage in the neurosurgical
      literature.

PMID- 12498502
TI  - Cervical cord tethering and congenital mirror movements: is it an association
      rather than a coincidence?
AB  - Two unusual cases of cervical cord tethering associated with mirror movements of
      the hands are presented. A brief discussion of the literature pertaining to
      mirror movements is included. It is concluded that the association of cervical
      cord tethering and mirror movements can be more than a coincidence.

PMID- 12498503
TI  - 'Mind the gap': resorption of a bone flap stored subcutaneously for 6 months.

PMID- 12498504
TI  - Fenestrated anterior cerebral artery.
AB  - Two rare cases of fenestrated anterior cerebral artery associated with aneurysms
      are described. The importance of identifying this unusual anatomical anomaly and
      its implication during surgery is discussed.

PMID- 12498505
TI  - Circular posterior-hinged craniotomy malignant cerebral oedema.

PMID- 12498506
TI  - The differential diagnosis of crystals in the retina.
AB  - Crystalline deposits in the retina may be associated with a wide variety of
      systemic disorders such as oxalosis, cystinosis, hyperornithinaemia and Sjogren
      Larsson syndrome. Refractile crystalline deposits may also be a manifestation of
      drug toxicity like the antineoplastic agent tamoxifen, the anesthetic
      methoxyflurane and the oral tanning agent canthaxanthine. Crystals may also occur
      in drug abusers who inject multiple crushed tablets of methadone or meperidine
      intravenously (talc retinopathy). The differential diagnosis of retinal crystals
      also includes primary ocular diseases like Bietti's crystalline retinopathy,
      calcified macular drusen, idiopathic parafoveal telangiectasis and longstanding
      retinal detachment. This article will review the most common causes of
      crystalline retinopathies, their etiologies, pathologies and clinical
      characteristics.

PMID- 12498507
TI  - A utility analysis correlation with visual acuity: methodologies and vision in
      the better and poorer eyes.
AB  - OBJECTIVE: To ascertain the correlation between visual acuity levels and
      ophthalmic utility values obtained using time tradeoff and standard gamble
      utility analysis methodologies. METHODS: Three hundred twenty-five consecutive
      patients with visual loss to 20/40 or less in at least one eye with predominantly
      vitreoretinal pathology were evaluated in a cross-sectional fashion using a
      standardized testing methodology to obtain ophthalmic time tradeoff and standard
      gamble utility values. Spearman correlation coefficients were employed to
      correlate the utility values with visual acuity in better seeing and poorer
      seeing eyes. RESULTS: The Spearman correlation coefficient for time tradeoff
      utility values and vision in the better seeing eye was 0.455 (p < 0.001), while
      that for time tradeoff utility values and visual acuity in the poorer seeing eye
      was 0.268 (p < 0.001). The coefficient for standard gamble utility values and the
      better seeing eye was 0.371 (p < 0.001), while that for standard gamble utility
      values and vision in the poorer seeing eye was 0.250 (p < 0.001). CONCLUSIONS:
      There is a greater correlation between ophthalmic utility values and vision in
      the better seeing eye, as versus vision in the poorer seeing eye. Time tradeoff
      ophthalmic utility values demonstrate a greater correlation with vision in the
      better seeing eye than do standard gamble utility values.

PMID- 12498508
TI  - Choroidal effusion and shallowing of the anterior chamber after adjunctive
      therapy with latanoprost in a trabeculectomized patient with angle closure
      glaucoma.
AB  - PURPOSE: Choroidal effusion and anterior chamber loss can occur in a
      trabeculectomized eye either spontaneously or following aqueous suppressant drug
      use. METHODS: A 50 year-old women with complaints of pain in the left eye (LE)
      was diagnosed as angle closure glaucoma. She was treated medically and underwent
      bilateral laser iridotomy. Because of high intraocular pressure it was decided to
      perform trabeculectomy. During the follow up period, the bleb became flat and
      after 3 months the IOP was again 24 mmHg with timolol maleate 0.5% and
      dorzolamide twice a day. Latanoprost was added to the therapy of the LE. RESULTS:
      12 days later the patient returned with pain and vision loss in her LE. The
      anterior chamber was diffusely narrow and ophthalmoscopy showed massive choroidal
      effusion. CONCLUSION: The possible mechanisms of this complication were
      discussed.

PMID- 12498509
TI  - Occurrence of catecholaminergic nerve fibers in the human uveoscleral tissue in
      conditions of normal and raised intraocular pressure.
AB  - The distribution of catecholaminergic nerve fibers (CNF) in human uveoscleral
      tissue was studied in six human eyes with normal intraocular pressure and in five
      eyes with increased pressure. The eyes with increased pressure had no visual
      field alterations and the patients did not have any glaucoma-related optic
      neuropathies. The amount of norepinephrine in these structures was also analysed.
      Catecholaminergic nerve fibers were detected by means of fluorescence microscopy
      and were counted using the quantitative analysis of images. Our results
      demonstrate that the occurrence of catecholaminergic nerve fibers (expressed in
      Conventional Units = C.U.) in human uveoscleral tissue is 15.4 +/- 1.6 C.U. in
      eyes with normal intraocular pressure. In eyes with increased intraocular
      pressure, these values were 12.2 +/- 1.2 C.U. Moreover, the amount of
      norepinephrine in tissue homogenates of the same eyes was evaluated and found to
      be 21.7 +/- 1.3 microg/gr tissue fresh weight of the human uveoscleral tissue in
      eyes with normal intraocular pressure. This value decreased to 18.8 +/- 1.1
      microg/gr tissue fresh weight in the same tissue in conditions of raised
      intraocular pressure. In these experiments, the small number of eyes examined
      made it difficult to draw general conclusions. However, the role of human
      uveoscleral tissue was emphasized by the rich catecholaminergic innervation. A
      decrease of catecholaminergic nerve fibers and norepinephrine occurs when
      intraocular pressure is elevated. The modifications of these parameters, involved
      in the sympathetic control of aqueous humor outflow, may support the hypothesis
      of a possible relevant role for the human uveoscleral tissue in different
      pathological conditions.

PMID- 12498510
TI  - Retinal vascular alterations associated with dome-shaped and mushroom-shaped
      choroidal melanomas.
AB  - PURPOSE: Retinal vascular abnormalities are associated with choroidal melanoma.
      Although tumor ischemia, resulting in soluble angiogenic factor production, is a
      proposed etiology of these abnormalities, other sources of ischemia may also
      contribute. Mushroom-shaped choroidal melanomas have increased loss of the
      overlying choriocapillaris and increased subretinal fluid when compared to dome
      shaped tumors; factors that may result in outer retinal ischemia, angiogenic
      factor production and resultant retinal vascular abnormalities. The differing
      amounts of retinal vascular abnormalities overlying dome-shaped compared to
      mushroom-shaped melanomas were determined to evaluate this hypothesis. METHODS:
      Retinal vascular abnormalities observed on fluorescein angiograms of eyes with
      choroidal melanoma were compared to the tumor configuration and presence of
      subretinal fluid. RESULTS: 23 eyes of 22 patients were included in the study.
      Retinal vascular abnormalities observed included dilated capillaries,
      telangiectatic capillaries, capillary nonperfusion, microaneurysms,
      neovascularization, lipid exudation and late staining of dye within the retina.
      Retinal vascular abnormalities were present in 4 of 14 eyes with dome-shaped
      tumors (29%) and in 8 of 9 eyes with mushroom-shaped tumors (89%). (Fisher's
      Exact Test, p = 0.009). Retinal vascular abnormalities were present in 2 of 10
      eyes without subretinal fluid (20%) and in 10 of 13 eyes with subretinal fluid
      (77%). (Fisher's Exact Test, p = 0.012). CONCLUSIONS: Retinal vascular
      abnormalities are associated with mushroom-shaped choroidal melanomas more
      commonly than dome-shaped tumors. Outer retinal ischemia may result from
      choriocapillaris loss or the presence of subretinal fluid, contributing to
      soluble angiogenic factor production and resultant retinal vascular abnormalities
      in these eyes. SUMMARY STATEMENT: Retinal vascular abnormalities are associated
      with mushroom-shaped choroidal melanomas more commonly than dome-shaped tumors.
      These retinal vascular abnormalities may be related to an increase in outer
      retinal ischemia associated with mushroom-shaped tumors.

PMID- 12498511
TI  - Silicone oil in the surgical treatment of endophthalmitis associated with retinal
      detachment.
AB  - PURPOSE: To investigate the use of silicone oil in the patients who had undergone
      vitrectomy for the treatment of endophthalmitis associated with retinal
      detachment. METHODS: Six consecutive cases of endophthalmitis associated with
      retinal detachment were included in the study. The mean age of the 4 males and 2
      females was 47.25 +/- 23.76 years. Endophthalmitis associated with retinal
      detachment occurred following perforating injuries in 4 eyes, pneumatic
      retinopexy in I eye and cataract surgery complicated with vitreous loss in I eye.
      Preoperative visual acuity was light perception-only in all eyes. Red reflex was
      absent in all eyes. All the patients underwent vitreous tapping, encirclement,
      vitrectomy, liquid-gas exchange, endolaser photocoagulation and silicone oil
      injection. RESULTS: Mean follow-up time was 14.3 +/- 7.20 months. The
      microorganisms that were isolated from the vitreous aspiration were
      Staphylococcus epidermidis in 3 cases, Staphylococcus aureus in 1 case. Remaining
      cases were culture negative. Retinal breaks could be found in 4 eyes.
      Inflammation subsided significantly at 5 days in all cases. Final retinal
      reattachment and treatment of endophthalmitis was achieved in 5 eyes at the end
      of follow-up. Final visual acuity was 20/40 in I case, counting finger in 4 cases
      and no light perception in 1 case. The postoperative complications were optic
      atrophy in 1 eye, epiretinal membrane in 2 eyes and phitisis bulbi in 1 eye.
      CONCLUSION: Silicone oil, a retinal tamponading agent that has antimicrobial
      activity, may have benefical effect in the surgical treatment of endophthalmitis
      associated with retinal detachment.

PMID- 12498512
TI  - Results of vitrectomy and the no-touch-technique using autologous adjuvants in
      macular hole treatment.
AB  - BACKGROUND: Anatomic and functional results of macular holes using vitrectomy and
      platelet-concentrate (PC) or autologous whole blood (WB) were investigated
      without peeling any epiretinal membrane in order to minimize retinal trauma.
      METHODS: 44 patients with macular holes stage II, III and IV underwent a
      vitrectomy with removal of posterior cortical vitreous (in stage II and III) and
      C2F6 gas endotamponade. No peeling of any epiretinal membrane or the ILM was
      performed. In 14 patients autologous WB was injected and in 30 patients
      autologous PC. The mean follow-up time was 9.3 months. RESULTS: An anatomic
      closure was observed in 36.4% of patients in the WB-group and in 93.9% of
      patients in the PC-group. SLO-microperimetry showed a reduction of absolute
      scotomas in 80% of the WB- and in 75% of the PC-group. In the WB-group 1 retinal
      detachment and 1 branch vein occlusion occurred; in the PC-group 3 retinal
      detachments, 1 central artery occlusion, 1 macular pucker, 1 cystoid macular
      edema, 1 late reopening and 1 secondary glaucoma were observed. In both groups no
      endophthalmitis occurred. CONCLUSION: If autologous platelet concentrate is
      available, high anatomic success rates can be achieved without aggressive
      membrane removal, which may cause retinal damage. Autologous whole blood cannot
      be recommended as an alternative adjunct for the treatment of macular holes
      without membrane removal.

PMID- 12498513
TI  - Pycnogenol for diabetic retinopathy. A review.
AB  - Diabetic retinopathy represents a serious health threat to a rapidly growing
      number of patients with diabetes mellitus. The retinal microangiopathy is
      characterised by vascular lesions with exudate deposits and haemorrhages causing
      vision loss. Pycnogenol, a standardised extract of the bark of the French
      maritime pine (Pinus pinaster), is known to increase capillary resistance.
      Pycnogenol has been tested for treatment and prevention of retinopathy in five
      clinical trials with a total number of 1289 patients since the late 1960's. All
      but one of these studies have been reported in French and German and, today, are
      of limited accessibility, giving the impetus for reviewing them in detail in this
      article. There were two open case studies and two double blind studies (one
      controlled against calcium dobesilate and another against placebo) and, finally,
      one multi-center field study with 1169 diabetics. All of these studies
      unequivocally showed that Pycnogenol retains progression of retinopathy and
      partly recovers visual acuity. Treatment efficacy of Pycnogenol was at least as
      good as that of calcium dobesilate. Pycnogenol was shown to improve capillary
      resistance and reduce leakages into the retina. Tolerance was generally very good
      and side effects were rare, mostly referring to gastric discomfort. In
      conclusion, treatment with Pycnogenol had a favourable outcome in the majority of
      the patients with diabetic retinopathy.

PMID- 12498514
TI  - Bilateral central retinal vein occlusions in a Chinese patient with HIV
      infection.
AB  - PURPOSE: To report a case of bilateral nonischemic central retinal vein
      occlusions as the initial presentation in a Chinese patient with HIV-infection.
      METHODS: Complete ophthalmological examination and fundus fluorescein angiography
      were performed in the eyes of this patient. RESULTS: Ophthalmic examination and
      fundus fluorescein angiography revealed bilateral nonischemic central retinal
      vein occlusions and optic disc edema in a 22-year-old man who was HIV-positive.
      The findings of fundus examination and fluorescein angiography were similar in
      both eyes. CONCLUSION: This case provides additional evidence that central
      retinal vein occlusion is probably part of the spectrum of HIV retinopathy.

PMID- 12498515
TI  - USTUR case 0259 whole body donation: a comprehensive test of the current ICRP
      models for the behavior of inhaled 238PuO2 ceramic particles. U.S. Transuranium
      and Uranium Registries.
AB  - An analysis of 238Pu in the whole body donation to the U.S. Transuranium and
      Uranium Registries (USTUR) is presented. This donor accidentally inhaled an
      unusual physical form of plutonium, predominantly the 238Pu isotope in the form
      of a highly insoluble ceramic. Along with six other workers accidentally exposed
      at the same time, this donor excreted little or no 238Pu in his urine for several
      months. Subsequently, however, and, with no further intakes, the urinary
      excretion of 238Pu by all of these workers increased progressively. Such a
      pattern of increasing urinary excretion of plutonium resulting from a single
      acute inhalation was unknown at the time. The subject of this study provided a
      unique opportunity to analyze not only the pattern of urinary excretion for 17 y
      following this unusual intake but also the complete distribution of 238Pu in his
      donated body tissues and skeleton at death. Radiochemical analyses of tissues
      from this whole body donation were used to perform critical tests of the
      applicability and accuracy of the respiratory tract model and the systemic
      biokinetic models for plutonium currently recommended by the International
      Commission on Radiological Protection. The respiratory tract model was applied to
      analyze the donor's long-term urinary excretion pattern. The facility provided by
      this model to represent progressive transformation of insoluble particles in the
      lungs into a more soluble form, applied in conjunction with the systemic
      biokinetic model, predicted the total amount of 238Pu measured in the donor's
      body to within 17% accuracy. The measured division of 238Pu between the donor's
      lungs and systemic organs was predicted to within 10%. Small adjustments to
      several rate constants in these models provided precise predictions of the
      absolute amounts of 238Pu in the lungs, thoracic lymph nodes, liver, red bone
      marrow, skeleton (including the distribution of 238Pu between trabecular and
      cortical bone matrices derived from the radiochemical analyses), kidneys, testes,
      and muscle. The resulting individual-specific parameters were applied to evaluate
      the equivalent dose rates and cumulative doses received by the donor's organs and
      the overall effective dose. Whereas these individual modifications to the ICRP
      models provided a more accurate representation of the distribution of dose
      between the donor's organs, it was determined that the ICRP models provided an
      adequate estimate of the overall effective dose.

PMID- 12498516
TI  - Estimation of actinide skeletal content in humans based on bone samples collected
      at autopsy.
AB  - The USTUR has developed simple linear and multiple regression models for
      estimating skeletal actinide concentrations on the basis of bone samples
      collected at autopsies of non-whole body tissue donors. Bone samples usually
      collected include a clavicle, the patella(e), one or more ribs, the sternum, and
      a vertebral wedge cut from within the abdominal cavity. The described models were
      derived by regression analyses with the analytical results from those bones and
      the entire skeletons of eight whole body donations to the USTUR. With the model,
      skeletal concentrations of 238Pu, (239+240)Pu, and 241Am can be estimated from
      wet or ashed actinide concentrations in one to five of the bones usually
      collected at autopsy and analyzed. Application of the models to a selected USTUR
      non-whole body donation (Case 0240) indicated that the skeletal actinide
      concentration estimates were reasonably precise and that there was good agreement
      between the results from individual bones with wet or ashed actinide
      concentrations. The USTUR will apply the model that is based on wet
      concentrations of bones to estimate skeletal concentrations of actinides in all
      non-whole body autopsy cases for the sake of consistency because of the large
      number of early cases for which ashed weights of bones were not recorded.

PMID- 12498517
TI  - Thyroid cancer incidence among adolescents and adults in the Bryansk region of
      Russia following the Chernobyl accident.
AB  - Thyroid cancer incidence in the Bryansk region, the most contaminated area of
      Russia after the Chernobyl accident, is analyzed for the residents aged 15-69 y
      at the time of the accident (about 1 million persons according to the 1989
      census) for the period from 1986 to 1998. Sex and age standardized incidence
      rates are presented and compared to the whole Russian population rates (SIR
      analysis). Also, a geographical correlation analysis is performed for incidence
      rates and mean thyroid doses at the district level, which provides a basis for
      preliminary estimation of radiation associated risks for the period 1991-1998 (to
      allow for a potential five year latent period). Thyroid doses were estimated
      based on the State official document "Methodology for reconstruction of dose from
      iodine radioisotopes in residents of the Russian Federation exposed to
      radioactive contamination as a result of the Chernobyl accident in 1986" (2000).
      Altogether, 1,051 thyroid cancer cases were detected in the Bryansk oncological
      dispensary from 1986 to 1998 and 769 from 1991 to 1998. Histological confirmation
      was available for 87% and 95% of these cases, respectively. Standardized
      incidence ratios (SIR) were 1.27 (95% CI = 0.92, 1.73) for the period 1986-1990
      and 1.45 (95% CI = 1.20, 1.73) for the period 1991-1998 for males and 1.94 (95%
      CI = 1.70, 2.20) and 1.96 (95% CI = 1.82, 2.1) for females. The excess relative
      risk per 1 Gy (using external control) estimate for the period 1991-1998 was -0.4
      (95% CI = -3.5, 2.7), -1.3 (95% CI = -2.8, 0.1) for males and females,
      respectively, and -0.6 (95% CI = -2.1, 0.8) for both sexes. Using internal
      controls, the excess relative risk (ERR(1Gy)) per unit dose of 1 Gy was found to
      be 0.7 with 95% CI (-2.3, 5.2) for males, -0.9 with 95% CI (-2.4, 0.8) for
      females and 0.0 with 95% CI (-1.4, 1.7) for males and females together. These
      results are discussed in the light of the quality of information available on
      thyroid cancer cases and screening campaigns carried out after the Chernobyl
      accident.

PMID- 12498518
TI  - A method for estimating occupational radiation doses subject to minimum detection
      levels.
AB  - Occupational radiation exposure is often coded as zero when the exposure dose is
      below the minimum detection level. This leads to an underestimation of the doses
      received by individuals and can lead to overestimates of risk in occupational
      epidemiologic studies. The extent of the dose underestimation is increased with
      the magnitude of the minimum detection level and the frequency of monitoring. The
      paper proposes a Bayesian approach to estimate the actual dose and the dose
      distribution parameter when the observed dose is subject to censoring due to
      minimum detection level. A Gibbs sampling algorithm is developed to implement the
      method. Simulation studies are used to evaluate the performance of the
      estimators. The method is applied to a sample of historical occupational
      radiation exposure data from the Oak Ridge National Laboratory.

PMID- 12498519
TI  - Computer simulation and experimental studies of implanted 210Po in glass
      resulting from radon exposure.
AB  - Retrospective radon exposure measurements rely on an understanding of how the
      depth distribution of the implanted activity in glass is influenced by processes
      such as implantation, diffusion, corrosion, and cleaning. In this study, the
      implantation depth of 210Po was found by step-wise etching with two different
      etchants to obtain the depth distribution. The depth profiles are compared with
      results from simulations using the SRIM computer program. Theoretically estimated
      distributions showed good agreement with experimental 210Pb (or 210Po) activity
      depth profiles obtained by sequential etching. The maximum depth of implanted
      activity was about 100 nm, and activity deeper than about 70 nm is associated
      with the second alpha decay from 214Po activity previously implanted in the glass
      matrix. However, there was no depth interval where the activity was solely due to
      a single decay from the surface. The results also show that measurement of the
      depth profile for both "old" and controlled 222Rn exposure

PMID- 12498520
TI  - Gas mixing for achieving suitable conditions for single point aerosol sampling in
      a straight tube: experimental and numerical results.
AB  - Experimental measurements of velocity and tracer gas concentration are taken in a
      straight tube to evaluate the effectiveness of mixing in achieving conditions as
      required by ANSI N13.1-1999 for single point extractive sampling from stacks and
      ducts of nuclear facilities. Mixing is evaluated for inlet turbulent intensities
      of 1.5%, 10%, and 20%, achieved by introducing various bi-plane grids, and for
      conditions generated by a commercial static gas mixer. The data obtained (at
      Reynolds number = 15,000) highlight the importance of inlet turbulence intensity
      in the process of turbulent dispersion of a dilute gas. The gas mixer does not
      introduce significant pressure losses and unlike bi-plane grids, the turbulence
      downstream of the mixer is not homogenous. A judicious choice of the release
      location that uses the large scale eddies and inhomogeneity of the turbulence
      ensures that the specified ANSI N13.1-1999 criteria are attained within 7
      diameters downstream of the duct inlet. This is significantly more effective than
      a bi-plane grid where even with 20% inlet intensity the criteria are met only at
      21 diameters downstream. The predictions of a proposed semi-empirical correlation
      match favorably with data. For example, at 18 diameters downstream with inlet
      intensities of 1.5% and 10%, the predicted coefficients of variation (COVs) of
      150% and 65% are close to the actual values of 154% and 50%; where the COV of a
      set of measurements is the ratio of the standard deviation of the set to its mean
      value. The corresponding results obtained using commercially available software
      are 141% and 12%. Results from a particle-tracking model show good qualitative
      trends, but they should not be used to determine compliance with the requirements
      of the ANSI standard.

PMID- 12498521
TI  - Cosmic-ray-induced neutron spectra and effective dose rates near air/ground and
      air/water interfaces in Taiwan.
AB  - The ground-level cosmic-ray neutrons were measured at various elevations from sea
      level to 4,000 m in Taiwan, where the vertical cutoff of geomagnetic rigidity is
      high. High-efficiency Bonner cylinders were used in the measurements. The
      measured results were used to normalize and confirm one-dimensional transport
      calculations for cosmic-ray neutrons near interfaces. According to these
      measurements and calculations, the ground-level neutron fluence rates, effective
      dose rates, and their altitude dependence in Taiwan were determined. As compared
      with that reported elsewhere, the appreciable differences both in their absolute
      values and associated dependence on altitude could be attributed to the
      substantial latitude effect. In addition, the energy spectra of cosmic-ray
      neutrons near air/ground and air/water interfaces were measured. The neutron
      fluence rate near the air/ground interface is greater than that near the
      air/water interface; however, the spectral shape is harder at the air/water
      interface than at the air/ground interface. The air/ground and in-flight spectra
      differ somewhat at low energies, especially in the thermal energy region, but the
      general shapes of the spectra are similar to each other. The influence of the
      difference in spectral shape on the evaluation of effective dose rate was
      investigated.

PMID- 12498522
TI  - Radon concentration measurements and personnel exposure levels in Bavarian water
      supply facilities.
AB  - As part of a study covering the whole of Bavaria, the southern most of Germany's
      16 states, water supply facilities were examined to determine the radon (222Rn)
      concentrations in ground water and indoor air and the radon exposure to the staff
      working in these buildings. Bavaria can be divided into ten geological regions of
      different geogenic radon potential. From each region, a number of water supply
      facilities proportional to the size of the region were selected for measurements.
      Over 500 of a total number of 2,600 water supply facilities were asked to take a
      1-L groundwater sample and expose several track-etch detectors in order to obtain
      the mean room concentration of the main staff work places. In addition, for a
      period of 2 mo, the personnel had to wear a track-etch detector during the time
      they spent in the supply facilities. The resulting measurements were then used to
      estimate their individual effective dose of radon and its progenies. In the East
      Bavarian crystalline region, the region of the highest geogenic radon potential
      within Bavaria, indoor radon gas concentrations of up to 400 kBq m(-3) were
      observed. About 10% of the process controllers in this region are subjected to an
      annual effective dose of more than 20 mSv. In the other Bavarian regions, only 2%
      of staff exposure levels exceed this limit. The correlation between the radon
      concentration measurements of the indoor air, the ground water, and individual
      personnel exposure levels was determined. The average ratio of the radon indoor
      air to the processed groundwater concentration is 0.14. But due to the different
      types of ventilation in the various supply facilities, there can be great
      variations in this figure. Therefore, there is no clear relationship between the
      groundwater and the indoor air concentration of a supply facility. This study
      also reveals no clear relationship between radon indoor air concentrations and
      the personnel exposure levels of a supply facility.

PMID- 12498523
TI  - Does soft tissue cancer affect the development of radionuclide-induced skeletal
      malignancy?
AB  - Data in the archives of the beagle project at the University of Utah were used to
      determine whether there might have been an association between the occurrence of
      soft tissue cancer and bone tumor (skeletal malignancy) among the dogs injected
      with bone-seeking radionuclides. In addition to comparing the numbers of animals
      with and without bone tumors and with and without soft tissue cancers, data on
      bone sarcomas and soft tissue sarcomas were compared. Longevity (postinjection
      survival) of the dogs was investigated. It appeared that survival (time between
      radionuclide injection and death) was important in the eventual expression of
      malignancies. There could not be established a possible susceptibility to
      skeletal malignancy associated with the occurrence of soft tissue cancer (or soft
      tissue sarcoma). We concluded that, although the literature reports an increased
      susceptibility for subsequent malignancies for individuals with naturally
      occurring or radiation-induced cancer, the data derived from this study do not
      confirm the concept that the appearance of soft tissue cancer is strongly
      associated with an increased risk of developing a radionuclide-induced skeletal
      malignancy.

PMID- 12498524
TI  - Health issues of ultraviolet tanning appliances used for cosmetic purposes.

PMID- 12498525
TI  - Ethics in orthopedic practice.

PMID- 12498526
TI  - Pharmacologic therapy for osteoarthritis.
AB  - Osteoarthritis is treated with a variety of pharmacologic therapies, including
      acetaminophen, traditional nonsteroidal anti-inflammatory drugs, cyclo-oxygenase
      2 inhibitors, intra-articular steroids, viscosupplements, glucosamine,
      chondroitin sulfate, capsaicin, and vitamins. In this review, we describe the
      clinical efficacy and side effects of these pharmaceuticals. Except for vitamins,
      each of these therapies is effective over the short-term when compared with
      placebo in controlled clinical trials. Risk-benefit analysis should be considered
      when prescribing these medications, as side effects are relatively common, and
      long-term efficacy is variable. In this review, we also examine current and
      future research on new medications--particularly matrix metalloproteinases and
      inducible nitric oxide synthase inhibitors--that may modify osteoarthritis.

PMID- 12498527
TI  - The femoral collodiaphyseal angle in Malawian adults.
AB  - We used unilateral anteroposterior radiographs to measure the collodiaphyseal
      angle of the hip in 368 Malawian adults--222 men and 146 women 18 to 76 years
      old. The angle ranged from 105 degrees to 144 degrees (mean, 121.09 degrees; SD,
      7.17 degrees). Results confirmed that the angle was wider in men than in women
      indicating dimorphism based on sex--but no Malawian could be identified by sex
      using the recommended demarking point method of Jit and Singh (1966). The
      importance of the angle and its usefulness to practicing orthopedic surgeons in
      this part of the world are emphasized.

PMID- 12498528
TI  - Fixed subtalar subluxation in a pediatric patient: an unusual entity.
AB  - Atraumatic, fixed subluxation of the subtalar joint in the pediatric population
      has not been described. This report describes such a case in a skeletally
      immature boy.

PMID- 12498529
TI  - Partial peroneus longus tendon rupture in professional basketball players: a
      report of 2 cases.
AB  - Partial tears of the peroneal tendons are rare. Partial longitudinal tears of the
      peroneus longus tendon are even more rare. We report on 2 professional basketball
      players who had partial peroneus longus tendon tears beneath the cuboid. A
      literature review and discussion of treatment is included.

PMID- 12498530
TI  - Trends in stresses on barrier integrity.

PMID- 12498531
TI  - Racial differences on skin barrier function.

PMID- 12498532
TI  - Topical niacinamide and barrier enhancement.

PMID- 12498533
TI  - Promoting production in the extracellular matrix without compromising barrier.

PMID- 12498534
TI  - Clinical situations conducive to proactive barrier enhancement.

PMID- 12498535
TI  - Bone regeneration with calcium sulfate: evidence for increased angiogenesis in
      rabbits.
AB  - Autologous bone is the preferred bone graft material because it carries proteins
      as bone-enhancing substrates, minerals, and vital bone cells. Calcium sulfate
      (CS) is a well-tolerated, biodegradable, osteoconductive bone graft substitute
      and is a reasonable alternative to autogenous bone graft. Blood vessels are an
      important component of bone formation and maintenance. The process of vascular
      induction is called angiogenesis, and it plays a key role in all regenerative
      processes. Bone tissue differentiation is related to the local presence of blood
      vessels. One method to evaluate the presence of blood vessels in a tissue is to
      count the microvessels to evaluate microvessel density (MVD). The aim of the
      present study was to conduct a comparative evaluation of microvessel density in
      sites treated with CS and autologous bone in rabbits, with or without e-PTFE
      nonresorbable membranes (Gore-Tex, Flagstaff, Ariz). Nine New Zealand rabbits,
      each weighing about 2.5 kg, were used in this experiment. Three 6-mm wide defects
      were created in each tibial metaphysis. The defects were filled in a random way.
      The defects of group 1 (3 rabbits) were filled with CS granules (Surgiplaster,
      Classimplant, Rome, Italy) and covered with e-PTFE membranes. The defects in
      group 2 (3 rabbits) were filled with CS granules (Surgiplaster). The defects in
      group 3 (3 rabbits) were filled with autologous bone. A total of 54 defects were
      filled (18 with CS and e-PTFE membranes, 18 with CS alone, and 18 with autologous
      bone). No postoperative deaths or complications occurred. All nine animals were
      sacrificed at 4 weeks. MVD results were as follows: in the first group, 9.88 +/-
      4.613; in the second group, 7.92 +/- 1.998; and in the third group, 5.56 +/-
      1.895. P = .000 was highly significant. Statistically significant differences
      were found between groups 1 and 3, 1 and 2, and 2 and 3. The presence of more
      blood vessels in the sites treated with CS could help to explain the good results
      reported in the literature with the use of CS.

PMID- 12498536
TI  - Implant replacement of congenitally missing lateral incisor: a case report.
AB  - The therapeutic goal of reconstruction dentistry is to provide our patients with
      a dentition that is in harmony with the patient's musculature and
      temporomandibular joints. Malocclusion can contribute to both muscular and joint
      dysfunction. This case report demonstrates the reconstruction of a malocclusion
      caused by a congenitally missing lateral incisor utilizing a combination of
      orthodontic treatment and a dental implant to replace the congenitally missing
      tooth.

PMID- 12498537
TI  - Placement of plate-form implants using osteotomes.
AB  - This article describes the use of osteotomes for the placement of plate-form
      implants. Comparison is made between the use of cylinders and the plate form as
      it relates to bone mass and resistant forces. It concludes by showing several
      cases in function.

PMID- 12498538
TI  - Bone regeneration graft materials.
AB  - This article focuses on the materials used for the regeneration, rather than
      repair, of the osseous support needed to anchor both teeth and implants. Once the
      bone was supportive, but now it is insufficient and must be restored.
      Specifically, the article examines different materials that aid in regeneration,
      as well as ones that do not. The pros and cons of osteoinduction and
      osteoconduction are compared. Autogenous, allographic, alloplastic, and
      xenographic materials are delineated and their intended purpose is described.
      These materials build the foundation of osseous support toward a functional
      future.

PMID- 12498539
TI  - Cortical bone spreader osteotome and method for dental implant placement.
AB  - This article describes an osteotome designed for placement of dental implants in
      narrow sites with less dense bone.

PMID- 12498540
TI  - Platelet-rich plasma: harvesting with a single-spin centrifuge.
AB  - This paper discusses the results recently seen by practitioners who use platelet
      rich plasma, as well as the practical considerations that they must make when
      considering whether to adapt their practice for its use. In this study, an
      average of a 358% increase in platelet concentration was achieved.

PMID- 12498541
TI  - CT data and its CAD and CAM utility in implant planning: part I.

PMID- 12498542
TI  - Circadian adaptation of aircrew to transmeridian flight.
AB  - BACKGROUND: Most research investigating the rate of circadian adaptation to
      transmeridian flight has focused on single, acute time zone transitions. Often
      however, aircrew experience compound time zone transitions, the physiological
      effects of which are not well understood. The primary aim of the current study
      was to investigate the circadian adaptation of a Royal Australian Air Force
      (RAAF) aircrew to several small time zone transitions using salivary melatonin
      onset as the marker of circadian phase. METHODS: Fifteen members of an RAAF
      aircrew collected saliva samples, sleep/wake records, and subjective alertness
      ratings during a 13-d surveillance patrol around the southwest Pacific Ocean.
      RESULTS: During the first 6 d of the surveillance patrol, the aircrew traveled
      3.5 time zones east and melatonin onset advanced by 3.8 h. During the next 6 d
      the aircrew traveled 2 time zones west, but melatonin onset did not shift. Night
      time sleep duration was shorter prior to workdays (6.4 h) than prior to rest days
      (8.4 h). Subjective alertness was not significantly affected by either the
      duration of night-time sleep prior to work, or the duration of flight.
      CONCLUSIONS: The melatonin onset results indicate that participants' body clocks
      adapted well to several small time zone transitions when initially traveling
      eastward, but did not adapt to a similar pattern of time zone transitions when
      subsequently traveling westward. This finding is contrary to expectations based
      on studies of single acute time zone transitions which indicate that adaptation
      to westward flight is more rapid than adaptation to eastward flight.

PMID- 12498543
TI  - Enhancement of preoxygenation for decompression sickness protection: effect of
      exercise duration.
AB  - INTRODUCTION: Since strenuous exercise for 10 min during preoxygenation was shown
      to provide better protection from decompression sickness (DCS) incidence than
      resting preoxygenation, a logical question was: would a longer period of
      strenuous exercise improve protection even further? HYPOTHESIS: Increased
      strenuous exercise duration during preoxygenation increases DCS protection.
      METHODS: There were 60 subjects, 30 men and 30 women, who were exposed to 9,144 m
      (4.3 psia) for 4 h while performing mild, upper body exercise. Before the
      exposures, each subject performed three preoxygenation profiles on different days
      in balanced order: a 90-min resting preoxygenation control; a 240-min resting
      preoxygenation control; and a 90-min preoxygenation including exercise during the
      first 15 min. The subjects were monitored at altitude for venous gas emboli (VGE)
      with an echo-imaging system and observed for signs and symptoms of DCS. RESULTS:
      There were no significant differences in occurrence of DCS following any of the
      three preoxygenation procedures. Results were also comparable to an earlier
      report of 42% DCS with a 60-min preoxygenation including a 10-min exercise. There
      was no difference between VGE incidence in the comparison of protection offered
      by a 90-min preoxygenation with or without 13 min of strenuous exercise. The DCS
      incidence following a 240-min resting preoxygenation, 40%, was higher than
      observed during NASA studies and nearly identical with the earlier 42% DCS after
      a 60-min preoxygenation including exercise during the first 10 min. CONCLUSION:
      The protection offered by a 10 min exercise in a 60-min preoxygenation was not
      increased with extension of the preoxygenation exercise period to 15 min in a 90
      min preoxygenation, indicating an upper time limit to the beneficial effects of
      strenuous exercise.

PMID- 12498544
TI  - Body temperature in sedentary adults during moderate exercise: no effect from
      exercise the day before.
AB  - BACKGROUND: Epidemiological findings show a continued presence of exertional heat
      injury during military basic recruit training. Current guidelines do not consider
      the carry-over effects of prior exercise or exposure to high ambient temperatures
      on the risk of succumbing to heat illness. HYPOTHESIS: From the epidemiological
      evidence we hypothesized that both prior exercise and exposure to hot
      environments on the day before would increase the core temperature response
      during exercise the next day. METHODS: Seven sedentary and non heat-acclimated
      men and women each performed eight randomized exposures involving treadmill
      walking for a maximum of 2 h every 2 wk. Two separate control trials at a wet
      bulb globe temperature (WBGT) of 22.5 degrees C and 26.5 degrees C consisted of
      exercise during the morning only. Six experimental trials involved successive
      days of exercise with trials on the second day at either a WBGT of 22.5 degrees C
      or 26.5 degrees C. All of the experimental trials involved walking during the
      first morning at a WBGT of 22.5 degrees C. Further, four of these trials included
      additional exercise in the afternoon at either a WBGT of 22.5 degrees C (two
      trials) or 29.5 degrees C (two trials). RESULTS: There was no impact of prior
      exercise on the day preceding the tests at either WBGT for any of the dependent
      measures. Rectal temperatures increased to 38.0 degrees C at the WBGT of 22.5
      degrees C and to 38.5 degrees C for trials at 26.5 degrees C. There were also no
      carry-over effects from exercise conducted during the preceding afternoon.
      CONCLUSIONS: Under situations where individuals are well hydrated, rested, and
      free of injury, illness, and drug use, repeated exercise bouts on successive days
      do not alter the thermoregulatory response to exercise.

PMID- 12498545
TI  - Investigation of rifle marksmanship on simulated targets during thermal
      discomfort.
AB  - BACKGROUND: Marksmanship has been reported to deteriorate during exposure to heat
      or cold, yet the effect of the resultant thermal strain in isolation of the
      inflicting thermal stress is not entirely clear. In most studies, the
      debilitating effects on marksmanship are confounded by an evolving thermal strain
      (in terms of body heat storage/debt). HYPOTHESIS: Thermal strain (hot and cold)
      should degrade marksmanship, more with moving targets than with conventional pop
      up targets that are deemed less challenging. METHODS: The 12 rifle-trained
      military reservists (7 men and 5 women) were tested on their marksmanship skills
      using a small arms simulator. Subjects conducted three trials in an
      environmentally controlled chamber, 1 wk apart in a counter-balanced order. Trial
      conditions were neutral (N; 22 degrees C), hot (H; 35 degrees C), and cold (C; 5
      degrees C), and all were preceded with an immersion in water to chest level to
      establish thermal strain (for H and C) or to maintain thermal neutrality prior to
      shooting. Subjects fired a C7 rifle at various targets during sixteen 5-min
      engagements over 2 h. Targets were presented either as moving in an urban setting
      or as pop-ups in a lane setting. Body temperatures, heart rate, saliva cortisol
      concentration, subjective ratings, and measures of marksmanship accuracy and
      precision were recorded and analyzed using a repeated measures design. RESULTS:
      Mean +/- SD of the rectal temperature during the shooting were 36.9 +/- 0.2
      degrees C, 37.7 +/- 0.3 degrees C, and 36.8 +/- 0.6 degrees C for N, H, and C,
      respectively (H > N, C). Corresponding hand temperatures were 31.5 +/- 1.2
      degrees C, 35.2 +/- 0.7 degrees C, and 19.4 +/- 3.0 degrees C (H > N > C). These
      body temperatures were consistent with the subjective indices of heat illness,
      cold discomfort, and muscle discomfort. Cortisol concentration and perceived
      exertion were higher during H. Surprisingly, thermal strain did not degrade
      marksmanship. Instead, some aspects of precision (horizontal displacement) and
      accuracy (shooting error) were poorer during N compared with H and C.
      CONCLUSIONS: Deep body temperatures not higher than approximately 37.9 degrees C
      and not less than 36.4 degrees C (accompanied by hand temperatures of not less
      than 19 degrees C) do not negatively affect rifle marksmanship performance, even
      if significant respective sensations of heat and cold are present.

PMID- 12498546
TI  - Development of an aviation safety locus of control scale.
AB  - INTRODUCTION: Individual differences in locus of control have be shown to be
      associated with differential risk for accident involvement among industrial and
      hospital workers. Previous research has also de onstrated that pilots are higher
      on internality than externality. HYPOTHESIS: This study was performed to assess
      individual differences on a new scale developed to assess locus of control with
      respect to aviation safe It was hypothesized that pilots would exhibit higher
      levels of internalility than externality on this new scale. METHODS: An existing
      safety locuss of control scale was modified to place the items in an aviation
      context, and the items were administered to a sample of approximately 480 pilots.
      Internality and externality subscales were created, and construct valid was
      assessed by correlating these subscales with measures of resignation and
      involvement in hazardous aviation events. RESULTS: The subscales exhibited
      acceptable internal consistency, and were negatively correlated (r = -0.419, p <
      0.001). Consistent with previous research, pilots exhibited substantially higher
      internality than externality. Correlation the subscales with the measures of
      resignation and involvement hazardous events supported the construct validity of
      the scale. DISCUSSION: Differences exist among pilots on the Aviation Safety
      Locusof Control scale that may be associated with increased accident risk. In its
      present form, the new scale might be employed as a self-awareness exercise for
      pilots or as a covariate in research investigating the effect of other factors on
      accident involvement.

PMID- 12498547
TI  - Neuroretinal function during mild systemic hypoxia.
AB  - PURPOSE: Few studies have investigated the effect of systemic hypoxia on the
      vascular and neural function of the human retina. Such studies can help us
      understand physiological responses to environmental hypoxia, as well as the
      pathophysiological mechanisms underlying certain ocular diseases. The objective
      of this study was to investigate the impact of mild systemic hypoxia on
      neuroretinal function through photopic flash electroretinogram (fERG) and
      oscillatory potential (OP) recordings. METHODS: The photopic fERGs and OPs were
      recorded in 18 healthy adults under conditions of mild systemic hypoxia. The
      retinal responses were recorded before, during, and after a 5-min period of
      breathing 12% oxygen (O2) in 88% nitrogen. The heart rate (HR), respiratory rate
      (RR), end-tidal carbon dioxide pressure (Petco2), and O2 saturation (SaO2) were
      measured throughout testing. The systemic blood pressure (BP) and intraocular
      pressure (IOP) were measured to derive the ocular perfusion pressure (OPP).
      RESULTS: Systemic hypoxia reduced SaO2 and PetCO2, increased HR but did not alter
      the RR or OPP. The a-wave amplitude and latency were not altered throughout
      testing. The b-wave amplitude decreased with hypoxia, whereas its latency was not
      affected. The amplitude of OP1, OP2, and OP4 remained stable throughout testing,
      whereas the amplitude of OP3 tended to decrease with hypoxia and was increased at
      the end of testing. The latency of OP1, OP3, and OP4 did not vary. The latency of
      OP2 was reduced at the end of testing. CONCLUSIONS: Our results show that mild
      systemic hypoxia alters the fERG b-wave and OPs but not the a-wave. This suggests
      that the outer retina in humans is more resistant to a mild systemic hypoxic
      stress than the inner retinal layers.

PMID- 12498548
TI  - Individual thermal profiles as a basis for comfort improvement in space and other
      environments.
AB  - BACKGROUND: The development of individualized countermeasures to address problems
      in thermoregulation is of considerable importance for humans in space and other
      extreme environments. A methodology is presented for evaluating minimal/maximal
      heat flux from the total human body and specific body zones, and for assessing
      individual differences in the efficiency of heat exchange from these body areas.
      The goal is to apply this information to the design of individualized protective
      equipment. METHODS: A multi-compartment conductive plastic tubing liquid
      cooling/warming garment (LCWG) was developed. Inlet water temperatures of 8-45
      degrees C were imposed sequentially to specific body areas while the remainder of
      the garment was maintained at 33 degrees C. RESULTS: There were significant
      differences in heat exchange level among body zones in both the 8 degrees and 45
      degrees C temperature conditions (p < 0.001). The greatest amount of heat was
      absorbed/released by the following areas: thighs (8 degrees C: -2.12 +/- 0.14
      kcal min(-1); 45 degrees C: +1.58 +/- 0.23); torso (8 degrees C: -2.12 +/- 0.13
      kcal min(-1); 45 degrees C: +1.31 +/- 0.27); calves (8 degrees C: -1.59 +/- 0.26
      kcal min(-1); 45 degrees C: +1.53 +/- 0.24); and forearms (8 degrees C: -1.67 +/-
      0.29 kcal x min(-1); 45 degrees C: +1.45 +/- 0.20). These are primarily zones
      with relatively large muscle mass and adipose tissue. Calculation of
      absorption/release heat rates standardized per unit tube length and flow rate
      instead of zonal surface area covered showed that there was significantly greater
      heat transfer in the head, hands, and feet (p < 0.001). The areas in which there
      was considerable between-subject variability in rates of heat transfer and thus
      most informative for individual profile design were the torso, thighs, shoulders,
      and calves or forearms. CONCLUSIONS: The methodology developed is sensitive to
      individual differences in the process of heat exchange and variations in
      different body areas, depending on their size and tissue mass content. The design
      of individual thermal profiles is feasible for better comfort of astronauts on
      long-duration missions and personnel in other extreme environments.

PMID- 12498549
TI  - Salivary immunoglobulin-A as a marker of stress during strenuous physical
      training.
AB  - BACKGROUND: Immunoglobulin-A in saliva (SIgA) has been proven to be decreased
      during periods of stress, a change that also correlates with increased disease
      risk. HYPOTHESIS: Concentration of SIgA is negatively associated with dietary
      deprivation, negative moods, and anxiety. METHODS: SIgA was evaluated as a marker
      of the severity of stress during a 19-day Royal Australian Air Force (RAAF)
      survival course, during which students experienced hunger, thirst, boredom,
      loneliness, and extreme heat and cold combined with demanding physical effort.
      There were 27 men and 2 women who participated. Students kept daily food diaries,
      from which daily intakes of energy and macronutrients were calculated. Saliva
      samples were collected on 9 d for the measurement of the ratio of SIgA to albumin
      (Alb). Students completed a health checklist and the State Anxiety Inventory on
      the same 9 d and the Profile of Mood States on 3 of the days. RESULTS: Dietary
      restriction, consumption of alcohol, body mass loss, occurrence of upper
      respiratory tract infection, and negative emotions were negatively associated
      with SIgA:Alb. CONCLUSION: SIgA:Alb is a useful marker of the severity of
      stresses encountered during stressful training.

PMID- 12498550
TI  - Pulmonary embolism at autopsy in a normal population: implications for air travel
      fatalities.
AB  - BACKGROUND: Much attention has been focused on the apparent risk to long-haul air
      travelers of venous thromboembolism [deep vein thrombosis (DVT) and pulmonary
      embolism (PE)], following a number of well-publicized cases. However, there is
      little epidemiological data to elucidate the problem. PE tends to be under
      diagnosed as a cause of death in the general population. This study sets out to
      establish the level of risk of fatal PE among long-haul passengers arriving in
      the UK, on the basis of a reappraisal of the role of PE in mortality in the
      general population. METHODS: Autopsies carried out at Gloucester in 1996-2000
      were reviewed to determine age-specific mortality rates for PE for West
      Gloucestershire. These rates were applied to long-haul air travelers arriving in
      the UK, for whom the number of passenger-years at risk were calculated, to
      estimate the expected numbers of deaths in this group. RESULTS: In 3764
      autopsies, PE was the primary cause of death in 221 cases (5.9%), while in 304
      (8.1%) it was present as an incidental finding. This suggests that PE was
      involved in approximately 13.9% of deaths, and is more common with age. Passenger
      years at risk per annum among long-haul passengers arriving in the UK were
      estimated (mid-range) at 21,830.482; it was anticipated that 6.55 deaths
      involving PEs, but not related to air travel, could be expected annually in this
      group. CONCLUSIONS: It appears that the risks of venous thromboembolism due to
      air travel are overstated. Some deaths are bound to occur inflight, but there is
      no evidence to suggest an increase, though clearly there are predisposing risk
      factors for DVT present on long journeys.

PMID- 12498551
TI  - Effect of head-out water immersion on neuromuscular function of the plantarflexor
      muscles.
AB  - INTRODUCTION: Electromyograms (EMGs) recorded during head-out immersion have
      demonstrated reduced signal amplitudes and decreased EMG/force ratios for both
      maximal and submaximal isometric contractions compared with measurements on dry
      land. Similar EMG changes have been found in spaceflight. HYPOTHESIS: This study
      was designed to examine neuromuscular function in the legs during immersion with
      special reference to reflex sensitivity. METHODS: Recordings were made during
      plantarflexion in air and water. EMGs were recorded from surface and/or internal
      electrodes on the soleus (SOL) and medial gastrocnemius (MG) muscles during
      maximal voluntary contraction (MVC). Hoffman and Achilles tendon reflexes were
      measured during submaximal plantarflexion (50% MVC) in air and water. RESULTS:
      During immersion, MVC decreased 13% while EMG amplitude of the plantarflexor
      muscles decreased by 29% and 35% for SOL and MG, respectively. A similar trend
      was observed in measurements of Hofman and Achilles tendon reflexes. CONCLUSIONS:
      Head-out immersion induced a deterioration of neuromuscular function, perhaps by
      triggering inhibitory mechanisms. The origin of these mechanisms seems to be
      related mainly to effects of partial weightlessness, but hydrostatic pressure
      should also be considered.

PMID- 12498552
TI  - Medical care system for NASA-Mir spaceflights.
AB  - A fundamental goal of space medicine is to maintain the health and fitness of
      spacecrews. Meeting this goal requires reliable, effective, up-to-date medical
      support systems for use in microgravity. This article describes some of the
      factors considered in the design and assembly of Russian and U.S. in-flight
      medical care systems. The successful mutual use of U.S. and Russian medications
      and medical equipment under the NASA-Mir program conclusively demonstrated the
      importance and advantages of cooperation among participating space agencies.
      Continued progress toward the integration of U.S. and Russian flight medical
      systems will further increase the effectiveness of the medical support of joint
      missions aboard the International Space Station.

PMID- 12498553
TI  - Transient neurological disorders during a simulated ascent of Mount Everest.
AB  - BACKGROUND: Transient neurological disorders are often observed at high altitude
      but are poorly documented under field conditions. The mechanism usually invoked
      is a hypocapnic vasoconstriction due to severe hypoxic hyperventilation. During a
      simulated ascent of Mount Everest in a hypobaric chamber by eight volunteer
      alpinists (Operation Everest III, Comex '97), three subjects presented
      neurological symptoms. We report here on the clinical observations and testing to
      detect mechanisms in addition to hypocapnic vasoconstriction. METHODS: The
      experiment was designed to investigate factors limiting physiological performance
      at altitude and the pathophysiology of acute mountain sickness. A retrospective
      analysis was made comparing the three cases of transient neurological disorder at
      high altitude (TNDHA) with the five subjects who had no neurological symptoms.
      RESULTS: Analysis of clinical and blood parameters showed no difference between
      cases and controls. The cases showed no neurological sequelae following the
      experiment and were normal on cardiac imaging. However, one case had a history of
      migraine in his youth, leading us to hypothesize that segmental vasoconstriction
      was a factor. In another case, gas bubbles were detected in the pulmonary artery
      by transthoracic echocardiography when he was symptomatic, suggesting that gas
      emboli may have played a role. All three cases shared a possible triggering
      factor in that each experienced hyperventilation alternating with straining
      against a closed glottis shortly before the onset of symptoms. CONCLUSION:
      Mechanisms other than hypocapnic vasoconstriction in hypoxia may be causal
      factors of TNDHA. The existence of triggering factors and evidence of a possible
      embolic mechanism should be further explored.

PMID- 12498554
TI  - Intraocular lens and corneal status following aircraft ejection by a USAF
      aviator.
AB  - Prior to 1967, military aviators who developed visually significant cataracts
      that affected visual performance were grounded. Those that ultimately required
      surgical removal were permanently grounded because of significant optical effects
      post-operatively. With the advent of contact lenses, a limited number of aircrew
      were returned to the cockpit because of improved optical factors provided by
      contacts post-cataract surgery. However, development of the intraocular lens
      (IOL) in the 1970s marked a major technological breakthrough that provided the
      potential to restore post-cataract surgical vision to near normal conditions.
      This case report is the first known occurrence of ejection from a high
      performance militaryaircraft by an aviator with an IOL. The success and stability
      of the IOL through this event provided additional clinical and operational
      information relative to the overall USAF experience with certain types of IOL
      approved for use in USAF aircrew. The aviator also sustained unexpected corneal
      foreign bodies due to the canopy fragmentation system.

PMID- 12498555
TI  - Cases from the aerospace medicine residents' teaching file. Case report of an
      aviator with focal myocarditis mimicking myocardial infarction with normal
      coronaries.
AB  - A military aviator was initially diagnosed with myocardial infarction following a
      viral syndrome. Confusion about recurrence of chest pain versus gastritis led to
      his continued cardiac patient status until this was clarified diagnostically. He
      was presumed to have had coronary vasospasm, and was treated with a calcium
      channel blocker. Absent his strong desire to return to flying duties, he may have
      continued in that diagnostic pathway indefinitely. After thorough aeromedical
      evaluation, resolved focal viral myocarditis was felt to be the most likely
      diagnosis and he was returned to military flying duties.

PMID- 12498556
TI  - Appropriate management of pilots diagnosed with depression.

PMID- 12498558
TI  - Aviation medicine course offered at Central American Agency for Aviation Safety.

PMID- 12498557
TI  - Alternative treatment for head pediculosis in confined environments and space
      travel.

PMID- 12498559
TI  - Total body negative pressure--revisited.

PMID- 12498560
TI  - Psychological effects of September 11th.

PMID- 12498561
TI  - The scientific basis for and efficacy of optometric vision therapy in
      nonstrabismic accommodative and vergence disorders.
AB  - BACKGROUND: For nearly 75 years, optometric vision therapy has been an important
      mode of therapy for both children and adults who manifested a range of
      nonstrabismic accommodative and vergence disorders. METHODS: In this article, the
      scientific basis for, and efficacy of, optometric vision therapy in such patients
      will be discussed. Using bio-engineering models of the oculomotor system as the
      conceptual framework, emphasis will be focused on studies that used objective
      recording techniques to directly assess therapeutically related changes in
      oculomotor responsivity. RESULTS AND CONCLUSIONS: The findings clearly support
      the validity of optometric vision therapy. Furthermore, the results are
      consistent with the tenets of general motor learning.

PMID- 12498562
TI  - Mediating a partnership dissolution.

PMID- 12498563
TI  - Outsourcing human resources management.

PMID- 12498564
TI  - National Glaucoma Awareness Month targets under-used Medicare screening benefit.

PMID- 12498565
TI  - Risk factors associated with colic in horses.
AB  - Many factors have been identified as risk factors for colic in horses in several
      epidemiological studies. The aim of our paper was to review the results of 12
      epidemiological studies, in order to assess the impact of each risk factor for
      colic. According to the literature, the factors that increase the risk of colic
      are feeding practices (type and quality of food, type and changes of feeding),
      the intrinsic factors of horses (sex, age and breed), management (type and
      changes of housing and activity), medical history (a previous colic,
      administration of a medical treatment) and parasite control (the presence of
      worms and type of deworming program). Several individual factors were
      incriminated as risk factors by all the studies. Nevertheless, the different
      studies did not always agree on the role of other risk factors. The conclusions
      were tightly related to several criteria in the selection of the study
      population, like the type of the epidemiological study, the number and the origin
      of horses included and the location of the study.

PMID- 12498566
TI  - In situ hybridization for the detection of the apxIV gene in the lungs of pigs
      experimentally infected with twelve Actinobacillus pleuropneumoniae serotypes.
AB  - The detection of the apxlV gene in lung tissues from pigs experimentally infected
      with the 12 major A. pleuropneumoniae serotype (1 to 12) reference strains was
      studied by in situ hybridization using a non-radioactive digoxigenin-labeled DNA
      probe. In situ hybridization produced a distinct positive signal in all pigs
      inoculated with the 12 A. pleuropneumoniae serotypes. Positive hybridization
      typically exhibited a dark-brown to black reaction product in intracellular and
      extracellular locations, without background staining. A strong hybridization
      signal was seen in degenerated alveolar leukocytes ("oat cells") adjacent to the
      foci of coagulative necrosis and in the alveolar spaces. The in situ
      hybridization methodology developed for the detection of the apxIV gene is a
      valuable tool for the diagnosis of porcine pleuropneumonia caused by A.
      pleuropneumoniae when only formalin-fixed tissues are submitted for diagnosis.

PMID- 12498567
TI  - Antioxidant systems and lymphocyte proliferation in the horse, sheep and dog.
AB  - To better define the species-specific antioxidant systems and to ascertain the
      influence of the intracellular redox status on the immune system of different
      animal species, we determined lymphocyte glutathione peroxidase (GSHPx) activity,
      plasmatic glutathione levels (GSH) and the effect of H2O2 on the responsiveness
      of lymphocytes to proliferative stimuli. Among the three species considered,
      sheep presented the lowest plasmatic GSH and the highest lymphocyte GSHPx
      activity. On the contrary, dogs showed an inverted pattern (high GSH - low
      GSHPx). Horses displayed intermediate values for both parameters analysed. The
      effect of H2O2 on the proliferative capacity of lymphocytes was the same for all
      three species; the 200 microM dose in particular was strongly inhibiting. Each
      species, however, showed different rates of inhibition: sheep exhibited the
      highest sensitivity to the antiproliferative effect of H2O2. Our results
      confirmed that high H2O2 concentrations (200 microM) are noxious for the cellular
      functions of all animals; however this effect is mediated by a rigorously species
      specific relationship between the intracellular reactive oxygen species (ROS) and
      the molecular systems involved in cell proliferation.

PMID- 12498568
TI  - Experimental infection of specific pathogen free (SPF) cats with two different
      strains of bartonella henselae type I: a comparative study.
AB  - Domestic cats are the reservoir of Bartonella henselae, the main causative agent
      of cat scratch disease. We compared B. henselae type I infection characteristics
      in 6 SPF cats infected with a feline strain (4.8 x 10(7) colony-forming units
      (CFU)/mL) and in 6 SPF cats infected with the reference Houston I strain (6.6 x
      10(6) CFU/mL to 9.6 x 10(7) /mL). All the cats inoculated with the feline strain,
      but none of the cats inoculated with B. henselae Houston I, developed a fever
      within 2-12 days (mean: 5.8 days) post inoculation (PI), which lasted for 1-2
      weeks. However, all 12 cats became bacteremic. The duration of bacteremia was
      significantly longer in the cats inoculated with the feline strain (mean: 237
      days) than in the cats inoculated with Houston I strain (mean: 60 days) (p <
      0.01). Five (83%) cats inoculated with the feline strain and none of the six cats
      inoculated with B. henselae Houston I had relapsing bacteremia (p = 0.02). IgG
      antibodies were detected by IFA within 1-2 weeks for both strains, but peaked
      later (week 10 versus week 3 PI) for the feline strain. By ELISA, using antigens
      of each B. henselae strain, all 12 cats developed Bartonella specific IgM and IgG
      antibodies, but the cats infected with B. henselae Houston I antigen yielded
      significantly lower optical density values (p < 0.05). By SDS-PAGE, PFGE and
      Western blotting, protein profile differences (84 to 89% homology) were observed
      between the two strains. If a feline vaccine is to be developed in order to
      prevent human infection, the choice of the vaccine strain will be critical, since
      major differences were identified even between strains belonging to the same
      sero/genotype.

PMID- 12498569
TI  - Nematophagous fungi as a biological control agent for nematode parasites of small
      ruminants in Malaysia: a special emphasis on Duddingtonia flagrans.
AB  - Approximately 2,800 fresh dung samples from animals, mainly ruminant livestock,
      were screened for the presence of nematophagous fungi in Malaysia. Arthrobotrys
      spp. was noted on numerous occasions, but only one isolate of Duddingtonia
      flagrans was made. For the purposes of producing sufficient quantities of this
      fungus for feeding trials in sheep, various, commonly available, cheap plant
      materials were tested as possible growth substrates. This showed that cereal
      grains (wheat, millet and rice) were the best media for fungal growth. Pen
      feeding trials were carried out using sheep, both naturally and experimentally
      infected with nematode parasites (predominantely Haemonchus contortus), to test
      the efficiency of D. flagrans when administered either in a grain supplement, or
      incorporated into a feed block. These showed that the fungus survived gut passage
      in sheep and that dose rates of approximately 1 x 10(6) D. flagrans spores /
      animal / day, reduced the percentage of infective larvae developing in faecal
      cultures by more than 90%. These results indicate that using D. flagrans as a
      biological control agent of nematode parasites, is a promising alternative to
      nematode parasite control of small ruminants in Malaysia, where anthelmintic
      resistance is now a major problem.

PMID- 12498570
TI  - Mechanisms controlling the oxygen consumption in experimentally induced
      hypochloremic alkalosis in calves.
AB  - The study was carried out on healthy Friesian calves (n = 10) aged between 10 and
      30 days. Hypochloremia and alkalosis were induced by intravenous administration
      of furosemide and isotonic sodium bicarbonate. The venous and arterial blood
      samples were collected repeatedly. 2,3-diphosphoglycerate (2,3-DPG), hemoglobin
      and plasmatic chloride concentrations were determined. The red blood cell
      chloride concentration was also calculated. pH, PCO2 and PO2 were measured in
      arterial and mixed venous blood. The oxygen equilibrium curve (OEC) was measured
      in standard conditions. The correspondence of the OEC to the arterial and mixed
      venous compartments was calculated, taking blood temperature, pH and PCO2 values
      into account. The oxygen exchange fraction (OEF%), corresponding to the degree of
      blood desaturation between the arterial and mixed venous compartments and the
      amount of oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were
      calculated from the arterial and mixed venous OEC, combined with PO2 and
      hemoglobin concentration. Oxygen delivery (DO2) was calculated using the arterial
      oxygen content, the cardiac output measured by thermodilution, and the body
      weight of the animal. The oxygen consumption (VO2) was derived from the cardiac
      output, OEF Vol% and body weight values. Despite the plasma hypochloremia, the
      erythrocyte chloride concentration was not influenced by furosemide and sodium
      bicarbonate infusion. Due to the alkalosis-induced increase in the 2,3-DPG, the
      standard OEC was shifted to the right, allowing oxygen to dissociate from
      hemoglobin more rapidly. These changes opposed the increased affinity of
      hemoglobin for oxygen induced by alkalosis. Moreover, respiratory acidosis,
      hemoconcentration, and the slight decrease in the partial oxygen pressure in
      mixed venous blood (Pvo2) tended to improve the OEF Vol% and maintain the oxygen
      consumption in a physiological range while the cardiac output, and the oxygen
      delivery were significantly decreased. It may be concluded that, despite reduced
      oxygen delivery, oxygen consumption is maintained during experimentally induced
      hypochloremic alkalosis in healthy 10-30 day old calves.

PMID- 12498571
TI  - Sternal recumbency or suspension by the hind legs immediately after delivery
      improves respiratory and metabolic adaptation to extra uterine life in newborn
      calves delivered by caesarean section.
AB  - The aim of this study was to evaluate the effect of body positioning immediately
      after delivery on respiratory and metabolic adaptation to extra-uterine life in
      newborn calves. One hundred and one Belgian White and Blue calves were delivered
      at term by an elective caesarean section and were assigned into three categories
      according to the body position imposed immediately after umbilical cord rupture:
      71 calves were placed in lateral recumbency; 16 calves were placed in sternal
      recumbency and 14 calves were suspended by the hind legs for less than 90 seconds
      (75 +/- 5 s). Following this initial body position, the calves were allowed to
      move without restraint. They were examined at birth, 5, 15, 30, 45 and 60
      minutes, and 2, 3, 6, 12 and 24 hours after birth by the following measurements:
      physical examination, heart rate, arterial blood gas analysis, pulmonary function
      tests using the esophageal balloon catheter technique, arterial and venous blood
      acid-base balance analysis, rectal temperature, jugular venous blood sampling for
      the determination of blood glucose, plasma lactate and serum cortisol
      concentrations, haematologic variables and passive immune transfer variables.
      Body positioning immediately after delivery clearly influenced respiratory and
      metabolic adaptation to extra-uterine life in term calves delivered by an
      elective caesarean section. Systematic sternal recumbency and suspension by the
      hind legs for less than 90 seconds immediately after umbilical cord rupture had a
      positive functional impact on postnatal pulmonary mechanics and gas exchange and
      on postnatal correction of mixed acidosis present at birth, contributing in turn
      to an enhanced passive immune transfer. These two body positions should be
      encouraged to improve adaptation at birth in healthy term calves delivered by an
      elective caesarean section. Evaluation of possible side-effects is required
      before application in severely asphyxiated calves.

PMID- 12498572
TI  - Flow and transport in unsaturated fractured rock: effects of multiscale
      heterogeneity of hydrogeologic properties.
AB  - The heterogeneity of hydrogeologic properties at different scales may have
      different effects on flow and transport processes in a subsurface system. A model
      for the unsaturated zone of Yucca Mountain, Nevada, is developed to represent
      complex heterogeneity at two different scales: (1) layer scale corresponding to
      geologic layering and (2) local scale. The layer-scale hydrogeologic properties
      are obtained using inverse modeling, based on the available measurements
      collected from the Yucca Mountain site. Calibration results show a significant
      lateral and vertical variability in matrix and fracture properties. Hydrogeologic
      property distributions in a two-dimensional, vertical cross-section of the site
      are generated by combining the average layer-scale matrix and fracture properties
      with local-scale perturbations generated using a stochastic simulation method.
      The unsaturated water flow and conservative (nonsorbing) tracer transport through
      the cross-section are simulated for different sets of matrix and fracture
      property fields. Comparison of simulation results indicates that the local-scale
      heterogeneity of matrix and fracture properties has a considerable effect on
      unsaturated flow processes, leading to fast flow paths in fractures and the
      matrix. These paths shorten the travel time of a conservative tracer from the
      source (repository) horizon in the unsaturated zone to the water table for small
      fractions of total released tracer mass. As a result, the local-scale
      heterogeneity also has a noticeable effect on global tracer transport processes,
      characterized by an average breakthrough curve at the water table, especially at
      the early arrival time of tracer mass. However, the effect is not significant at
      the later time after 20% tracer mass reaches the water table. The simulation
      results also verify that matrix diffusion plays an important role in overall
      solute transport processes in the unsaturated zone at Yucca Mountain.

PMID- 12498573
TI  - A large-scale experiment on mass transfer of trichloroethylene from the
      unsaturated zone of a sandy aquifer to its interfaces.
AB  - A large-scale experiment was conducted to investigate the transport of
      trichloroethylene (TCE) vapors in the unsaturated zone and to determine the mass
      transfer to the groundwater and the atmosphere. The experiment involved injection
      of 5 1 of TCE in the unsaturated zone under controlled conditions, with
      multidepth sampling of gas and water through the unsaturated zone and across the
      capillary zone into underlying groundwater. The mass transfer of TCE vapors from
      the vadose zone to the atmosphere was quantified using a vertical flux chamber. A
      special soil water sampler was used to monitor transport across the capillary
      fringe. Experimental data indicated that TCE in the unsaturated zone was mainly
      transported to the atmosphere and this exchange reduced significantly the
      potential for groundwater pollution. The maximum measured TCE flux to the
      atmosphere was about 3 g/m(2)/day. Observed and calculated fluxes based on
      vertical TCE vapor concentration gradients and Fick's law were in good agreement.
      This confirms that TCE vapor transport under the experimental conditions was
      governed essentially by molecular diffusion. TCE vapors also caused a lower, but
      significant contamination of the underlying groundwater by dispersion across the
      capillary fringe with a corresponding maximum flux of about 0.1 g/m(2)/day. This
      mass transfer to groundwater is partly uncertain due to an inadvertent entry of
      some nonaqueous phase liquid (NAPL) from the source area into the saturated zone.
      Application of an analytical solution to estimate the TCE flux from the
      unsaturated zone to the groundwater indicated that this phenomenon is not only
      influenced by molecular diffusion but also by vertical dispersion. The mass
      balance indicates that, under the given experimental conditions (e.g. proximity
      of the source emplacement relative to the soil surface, relatively high permeable
      porous medium), nearly 95% of the initial TCE mass was transferred to the
      atmosphere.

PMID- 12498574
TI  - The effects of surfactant formulation on nonequilibrium NAPL solubilization.
AB  - Surfactant-enhanced aquifer remediation (SEAR) involves the injection of
      surfactant solutions into aquifers contaminated with nonaqueous phase liquids
      (NAPL). Batch and column experiments were used to assess the effect of surfactant
      formulation on the rate of NAPL solubilization. The experimental variables were
      surfactant type, surfactant concentration, electrolyte concentration, and
      cosolvent concentration. Model equations were proposed and solved to describe
      solubilization under the conditions of each type of experiment. Using these
      models, a solubilization rate constant, kappa(b), and an overall mass transfer
      rate coefficient, kappa, were estimated from the batch and column experiments,
      respectively. The solubilization rate constant was consistently sensitive to
      surfactant type, surfactant concentration, and electrolyte concentration. The
      estimated solubilization rate constants varied over two orders of magnitude. The
      results of the column experiments also were sensitive to the surfactant
      formulation. Variations in the fitted mass transfer rate coefficient parameter,
      beta(0), were related to variations in the surfactant formulations. A comparison
      between the results of the batch and column experiments yields an apparent
      relationship between beta(0) and kappa(b). This relationship suggests that the
      mass transfer rate coefficient is directly related to the formulation of the
      surfactant solution.

PMID- 12498575
TI  - A micromodel analysis of factors influencing NAPL removal by surfactant foam
      flooding.
AB  - A methodology to study the trichloroethylene (TCE) and dodecane removal in porous
      media by surfactant foams (SF) was presented by using etched-glass micromodels.
      The purpose of this work was to systematically evaluate the impact of various
      physicochemical factors such as gas fraction (GF), surfactant concentration, pore
      structure and nonaqueous phase liquid (NAPL) types on NAPL removal during SF
      flooding. The TCE displacement by SF was dependent on the gas fraction of SF. Low
      GFs (50% and 66%) were more efficient for TCE removal and sweep efficiencies than
      a high GF (85%). An increase in TCE removal was observed with increasing
      surfactant concentration at a fixed GF. TCE removal by SF flooding appeared to be
      dependent more to the value of Capillary number rather than to the concentration
      of surfactant solution. The effect of the pore heterogeneity was evaluated by
      employing two different types of micromodels. The Capillary number is an
      important parameter in the determination of sweep efficiency or gas saturation of
      SF in a nonhomogeneous porous medium. However, the TCE removal from a
      nonhomogeneous porous medium may not be associated with sweep efficiency. The
      initial configuration of residual TCE blobs in a nonhomogeneous porous medium
      would also be influential in displacing TCE. Sweep efficiencies and pressure
      responses of two NAPL systems (TCE and dodecane) were monitored to evaluate foam
      stability when the foam contacts the NAPLs. Stable foam contacting with TCE is
      implied, while it appears that dodecane cause the SF to collapse. All results
      indicate that the Capillary number (a ratio of viscous forces to capillary
      forces) is the most important parameter for TCE removal by SF flooding.
      Micromodel visualizations of water, surfactant and SF floods were showed and also
      discussed.

PMID- 12498576
TI  - Quantification of mass fluxes and natural attenuation rates at an industrial site
      with a limited monitoring network: a case study.
AB  - At many "real world" field sites, the number of available monitoring wells is
      limited due to economic or geological reasons. Under such restricted conditions,
      it is difficult to perform a reliable field investigation and to quantify primary
      lines of evidence for natural attenuation (NA), like the documentation of a
      decrease of contaminant mass flux in flow direction. This study reports the
      results of a groundwater investigation at a former manufactured gas plant
      situated in a Quaternary river valley in southwest Germany. The location,
      infrastructure and aquifer setting are typical of many industrial sites in
      Germany. Due to difficult drilling conditions (coarse glaciofluvial gravel
      deposits and an anthropogenic fill above the aquifer), only 12 monitoring wells
      were available for the investigation and localisation of the contaminant plume.
      These wells were situated along three control planes (CP) downgradient from the
      contaminant source, with four wells along each plane. Based on the sparse set of
      monitoring wells, field scale mass fluxes and first-order natural attenuation
      rate constants of benzene, toluene, ethylbenzene, and o-xylene and p-xylene
      (BTEX) and low molecular weight polycyclic aromatic hydrocarbons (PAH) were
      estimated utilizing different point scale and also a new integral investigation
      method. The results show that even at a heterogeneous site with a sparse
      monitoring network point scale investigation methods can provide reliable
      information on field scale natural attenuation rates, if a dependable flow model
      or tracer test data is available. If this information is not available, only the
      new integral investigation method presented can yield adequate results for the
      quantification of contaminant mass fluxes under sparse monitoring conditions.

PMID- 12498577
TI  - Application of the method of temporal moments to interpret solute transport with
      sorption and degradation.
AB  - In this note, we applied the temporal moment solutions of [Das and Kluitenberg,
      1996. Soil Sci. Am. J. 60, 1724] for one-dimensional advective-dispersive solute
      transport with linear equilibrium sorption and first-order degradation for time
      pulse sources to analyse soil column experimental data. Unlike most other moment
      solutions, these solutions consider the interplay of degradation and sorption.
      This permits estimation of a first-order degradation rate constant using the
      zeroth moment of column breakthrough data, as well as estimation of the
      retardation factor or sorption distribution coefficient of a degrading solute
      using the first moment. The method of temporal moment (MOM) formulae was applied
      to analyse breakthrough data from a laboratory column study of atrazine,
      hexazinone and rhodamine WT transport in volcanic pumice sand, as well as
      experimental data from the literature. Transport and degradation parameters
      obtained using the MOM were compared to parameters obtained by fitting
      breakthrough data from an advective-dispersive transport model with equilibrium
      sorption and first-order degradation, using the nonlinear least-square curve
      fitting program CXTFIT. The results derived from using the literature data were
      also compared with estimates reported in the literature using different
      equilibrium models. The good agreement suggests that the MOM could provide an
      additional useful means of parameter estimation for transport involving
      equilibrium sorption and first-order degradation. We found that the MOM fitted
      breakthrough curves with tailing better than curve fitting. However, the MOM
      analysis requires complete breakthrough curves and relatively frequent data
      collection to ensure the accuracy of the moments obtained from the breakthrough
      data.

PMID- 12498578
TI  - Exposure and respiratory health in farming in temperate zones--a review of the
      literature.
AB  - To review studies in farming populations from temperate zones focusing on: (1)
      exposure to dust, bacteria, moulds, endotoxin, and ammonia, (2) sensitisation to
      common airborne allergens, (3) prevalence, incidence and risk factors of chronic
      bronchitis, asthma and bronchial hyperresponsiveness, and (4) measurements of
      lung function. Working in animal housings can be associated with exposure to
      organic dust, bacteria, moulds, endotoxin, and ammonia in concentrations that can
      induce cellular and immunological responses and result in respiratory diseases.
      Working in poultry housing might be associated with higher exposures to dust,
      bacteria, and ammonia than in swine and cow housings, and endotoxin exposure
      seems to be higher in North America than in Europe. Working exposure might
      influence the domestic area on farms, and there might be a protective effect of
      being raised on a farm regarding sensitisation and allergic diseases.
      Sensitisation to mites seems to be the most prevalent of the common inhalant
      allergens. Chronic bronchitis is frequent and data suggests that it is work
      related in farmers. Findings concerning asthma are less uniform, and data
      regarding bronchial hyperresponsiveness are too sparse and inconsistent to
      evaluate the effect on farming. Several risk factors have been described, and age
      is shared for all three clinical manifestations, while male gender, atopy,
      smoking, pig farming, and animal production are common risk factors for chronic
      bronchitis and asthma. FEV(1), and FEV(1)/FVC seems to be reduced in farmers, and
      longitudinal studies indicate an increased annual loss in FEV(1) in farmers,
      especially in pig farmers. The increased annual decline has been associated with
      lung function, bronchial hyperresponsiveness, smoking, automatic dry feeding
      systems, and endotoxin. Despite studies with methodological weaknesses,
      heterogenity in sampling times, measurement techniques, equipment, and diagnostic
      criteria, the review has revealed that the exposure to organic dust in farming
      can be substantial and might lead to respiratory diseases and increased annual
      loss in lung function. Working exposure seems to influence the domestic area in
      farms, and being raised on a farm might have a protective effect regarding
      sensitisation and allergic diseases.

PMID- 12498579
TI  - Canine borreliosis--epidemiology and diagnostics.
AB  - Ixodes ticks, vectors of B. burgdorferi, carry the spirochaetes to a number of
      vertebrates; however in natural conditions only the species from outside the
      forest biotope display the clinical form of borreliosis, mainly humans and dogs.
      In dogs, B. burgdorferi s.l. has been implicated as a cause of various disorders
      often resembling those observed in human borreliosis, including polyarthropathy,
      anorexia, malaise, and neurological dysfunction. In areas infested with I.
      ricinus, and I. dammini in the USA and known to be endemic for Lyme disease,
      veterinarians may suspect borreliosis in dogs with limb/joint disorders. In
      serological diagnosis, it should be considered that the occurrence of even
      specific antibodies does not necessarily mean the active disease or primary
      exposition to the pathogen. Studies on antibody titers in the sera of dogs either
      naturally or experimentally infected, and on their associations with clinical
      symptoms, indicate the same limitations of serological tests as in the diagnostic
      of human Lyme disease; therefore, PCR is the most appropriate method of
      diagnosis.

PMID- 12498580
TI  - Investigations on ecological effects of heavy metal pollution in Hungary by moss
      dwelling water bears (Tardigrada), as bioindicators.
AB  - The authors demonstrate a possible relationship between the concentrations of
      metals (Cd, Cr, Cu, Fe, Ni, Pb, V, Zn) measured in mosses and the composition of
      Tardigrade species detected in the same samples. Cushions of Hypnum cupressiforme
      were collected at 18 sites distributed in the whole of Hungary to estimate the
      background air pollution, then analyzed by ICP-AES to determine the
      concentrations of heavy metals. Data reflect the expected correlation; elevated
      heavy metal contents decrease the number of water bear species and of specimens,
      and abundance of Tardigrada depends strongly on air pollution. Higher
      concentrations of cadmium and chromium seem to have particularly damaging and
      toxic influence on community structure. As the biologically relevant effects of
      pollution can only be evaluated by carrying out measurements on the organisms
      themselves, our method applied species of Bryophyte and of Tardigrade, as
      bioindicators were appeared to be an adequate method to show the effect of air
      pollution on abundance of water bears.

PMID- 12498581
TI  - Antigenic and allergenic properties of Amaranthus Spinosus pollen--a commonly
      growing weed in India.
AB  - Amaranthus spinosus (Fam. Amaranthaceae) is an important aeroallergen in India
      and grows commonly in different parts of the country. In spite of its clinical
      significance in Type I hypersensitivity disorders, the antigenic and the
      allergenic properties of the pollen have not been systematically resolved. We
      investigated antigenic and allergenic properties of 5 pollen samples of
      Amaranthus spinosus collected from the Delhi area at fortnightly intervals. The
      protein content did not exhibit statistically significant variability. However,
      samples collected during the peak flowering season showed higher protein content.
      Biochemical characterization of samples showed multiple protein fractions by IEF
      and SDS-PAGE analysis. Samples collected during peak season showed a slightly
      higher number of bands (22) in the mw range of 14-70 kD. Seven protein fractions
      of 70, 66, 60, 50, 40, 30 and 14 kD were observed to have IgE binding
      capabilities and 9 were treated as allergenic. The observations will be helpful
      in standardizing pollen antigens for diagnosis and immunotherapy in India.

PMID- 12498582
TI  - Seroprevalence of anti-Borrelia burgdorferi antibodies in sheep and goats from
      mountainous areas of Slovakia.
AB  - In the present study, domestic animals such as sheep and goats from eastern
      Slovakia were screened for the presence of anti-Borrelia antibodies.
      Seroprevalence in 181 sheep and 65 goats were carried out in 1999 and 2000.
      Modified ELISA method was used for detection of anti-Borrelia IgG antibodies.
      Seroprevalence obtained was 15.8% and 17.5% in 1999 and 2000 respectively in
      sheep, whereas in goats it was 17.2% and 19.4% respectively. The results suggest
      that these domestic species have potential to transmit the disease to other
      animals. Though the role of sheep and goats in Lyme disease has not yet been
      documented, there is great possibility of transmission of the causative agent via
      co-feeding to human beings.

PMID- 12498583
TI  - Hearing loss among private farmers in the light of current criteria for
      diminished sense of hearing.
AB  - The study covered a group of 128 private farmers aged 28-65 (mean age 47.2) who
      had a period of occupational activity of 11-40 years (23.9 years average). The
      evaluation of hearing capability was based on 2 calculated values: PTA (mean from
      frequency: 0.5; 1; 2 and 3 kHz) and HFA (mean from 3; 4; and 6 kHz).
      Statistically significant differences in mean hearing loss were observed between
      the 2 groups in the study: farmers-control group (p < 0.001). The value of 20 dB
      was adopted as a criterion of the deterioration of hearing. This criterion was
      exceeded in 78% of farmers examined--within the range of high frequencies (HFA),
      and in 45 % of farmers within the range of medium frequencies (PTA). In the
      control group, abnormal hearing loss was noted in 17% of people only for mean HFA
      value. In the group of farmers a significant correlation was noted between
      hearing loss (PTA and HFA) and age, as well as period of occupational activity.
      It was statistically confirmed that the most significant decrease in hearing
      occurred during the age interval up to the age of 50 and during the period of
      occupational activity of up to 30 years. The results of the study confirmed that
      noise present in the agricultural environment is the primary cause of the
      decrease in hearing among private farmers.

PMID- 12498584
TI  - A controlled intervention study concerning the effect of intended temperature
      rise on house dust mite load.
AB  - In epidemiological studies, increased indoor temperature--producing a lower
      relative humidity--is associated with low house dust mite (HDM) load. Twenty
      eight dwellings were allocated for either intervention (12/15 completed) or
      control (11/13 completed). In the intervention group, participants were asked to
      increase the bedroom temperature by at least 3 degrees C compared to the self
      assessed temperature of the previous winter. Dust samples were repeatedly
      collected from mattress and floor, and bedroom temperature and relative humidity
      were recorded hourly throughout one year. Dust was analysed for allergen (Der f 1
      + Der p 1 + Der m 1 = Der 1) by ELISA and HDMs were counted. Changes in mite and
      in mite allergen concentration were the same in the control and intervention
      groups, and measured temperatures did not differ during intervention period in
      the groups (18 degrees C and 19 degrees C). Groups turned out not to be
      comparable with respect to initial (self-assessed) bedroom temperature (lowest in
      the intervention group). There was a significant seasonal variation, with doubled
      Der 1 concentrations in dust collected in July-November compared to January-May
      samples. No effect was obtained on mites or mite allergens, but this may be due
      either to a general lack of effect of increase in bedroom temperature, or to an
      insufficient increase in temperature in our intervention group. Seasonal
      variations in HDM and HDM allergens must be accounted for when data on exposure
      are interpreted.

PMID- 12498585
TI  - Disorders of the musculoskeletal system among dentists from the aspect of
      ergonomics and prophylaxis.
AB  - The profession of dentist exposes them during their work to many burdensome and
      harmful factors. The irrational posture adopted by dentists during their work
      causes discomfort and disorders of the musculoskeletal system and the peripheral
      nervous system. The methods and organization of the work of Polish dentists were
      evaluated from the aspect of ergonomics, with regard to reported by them painful
      disorders connected with the musculoskeletal system, with the aim of applying
      proper methods of treatment and prophylaxis. The study showed that dentists
      worked in conditions which generally produced disorders of the musculoskeletal
      system. As a result, the long working time in the course of a day was used
      irrationally from the point of view of ergonomics, which over the years of work
      consequently increased the number of disorders of the musculoskeletal system.
      Dentists must make use of various forms of treatment. The effectiveness of
      prophylaxis concerning the musculoskeletal system were only partly assessed by
      the respondents through questionnaire. Most dentists are convinced of the
      effectiveness of physical activity in prophylaxis which they carry out
      themselves.

PMID- 12498586
TI  - The prevalence of piroplasms in a population of Ixodes ricinus (Acari: Ixodidae)
      from north-western Poland.
AB  - Developmental forms of Babesia spp. were studied in isolated salivary glands of
      Ixodes ricinus, subjected to the Feulgen reaction. The same ticks were also hosts
      to Babesia microti, which was determined by PCR amplification with primers
      specific to the fragment of a gene encoding the nuclear small sub-unit ribosomal
      RNA (SS-rDNA). Presence of Babesia spp. was recorded in the salivary glands of
      59.9% of ticks collected, both in nymphs and adults. PCR reactions specific to
      Babesia microti were positive in 1.9% of nymphs.

PMID- 12498587
TI  - Occurrence of enterotoxigenic Staphylococcus aureus in food.
AB  - Gastroenteritis is one of the most frequent microbial diseases, which is caused
      by the ingestion of food contaminated with staphylococcal enterotoxins. In our
      study, the production of staphylococcal enterotoxins A, B (SEA, SEB) and the
      presence of respective staphylococcal enterotoxin genes were investigated in the
      field S. aureus isolates obtained from foods and food industry manufactures in
      East Slovakia. Radioimmunoassay (RIA), polymerase chain reaction (PCR) and dot
      blot hybridisation were used for examination. The ability to synthesise
      enterotoxins was found in 20 (39.2%) of the total number of 51 isolates.
      Production of SEA was recorded in 3 (5.9%), production of SEB in 12 (23.5%) and
      production SEA together with SEB in 5 (9.8%) staphylococcal isolates. Nine
      (47.4%) sheep cheese isolates of the total number of 19 produced enterotoxins,
      especially SEB (36.8%). S. aureus isolates from pasta were enterotoxigenic in 6
      cases (33.3%). The synthesis of enterotoxins was not detected in Bryndza cheese
      and sausages isolates. One enterotoxigenic isolate was obtained from smears of
      technological equipment and 4 isolates from throat and nasal swabs. No
      differences in results were recorded between RIA and PCR as well as PCR and dot
      blot hybridisation. Our results suggest that it is of special importance to
      follow the presence of enterotoxigenic S. aureus strains in foodstuffs,
      especially for protecting the consumers from food poisoning.

PMID- 12498588
TI  - Toxin producing micromycetes on fruit, berries, and vegetables.
AB  - In 1999-2001 the investigations on mycological state of stored and sold fruit,
      berries, and vegetables grown in Lithuania and imported from other countries were
      performed. The samples of foodstuff were taken from storehouses, various
      supermarkets, and market places. Such ecological conditions lead to a rapid
      spreading of micromycetes and contamination of other articles of food stored and
      sold nearby. On fresh fruit and berries the development of microorganisms is
      slow. However, microorganisms penetrate into internal tissues of berries and
      fruit, thus becoming difficult to notice visually. Some microorganisms,
      especially micromycetes of some species belonging to the Penicillium Link,
      Aspergillus Mich. ex Fr., and other genera, are able to produce secondary
      metabolites (mycotoxins) of various compositions that are toxic to plants,
      animals, and humans. Therefore, the ability of micromycetes to synthesise and
      excrete toxic secondary metabolites was examined. Considering this issue, 393
      micromycete strains ascribed to 54 genera and 176 species were tested. 46 strains
      were identified as active producers of toxic substances and were selected for
      further examinations. Most of them belonged to the Penicillium, Aspergillus and
      Fusarium genera. Their detection frequency on the investigated berries, fruit,
      and vegetables was determined, and the impact upon warm-blooded animals (BALB/c
      mice) was tested. Significant changes of the internal organs and blood
      composition were found in mice infected with toxic micromycetes. In conclusion,
      it was evidenced that more than 10% of micromycete strains developing on
      incorrectly-preserved fruit, berries and vegetables, produce toxic secondary
      metabolites that pose a potential health hazard for people eating or handling the
      foodstuff.

PMID- 12498589
TI  - Hematological alternations after pyrethroids poisoning in mice.
AB  - The aim of the study was evaluation of the effect of alpha-cypermethrin,
      deltamethrin or fenvalerate poisoning on hematological parameters in male and
      female Swiss mice in sub-acute poisoning. All pyrethroids examined, irrespective
      of the dose and sex of animals, caused an increase in the number of leukocytes in
      peripheral blood. In alpha-cypermethrin poisoning no changes in the hematological
      parameters were observed in male mice, whereas in female animals the
      administration of a lower alpha-cypermethrine dose resulted in an inhibition, and
      a higher dose in mobilization of hemopoietic system. In male mice poisoned with
      deltamethrin or fenvalerate, mobilization of the hemopoietic system was noted. No
      changes in the hematological parameters were observed in female mice poisoned
      with a higher deltamethrin dose. In female animals which were administered a
      lower deltamethrin dose or fenvalerate a decrease was noted in the number of
      erythrocytes, as well as hemoglobin and hematocrit levels.

PMID- 12498590
TI  - Prevalence and risk factors for airway diseases in farmers--summary of results of
      the European Farmers' Project.
AB  - The aim of the European Farmers' Project was to determine prevalence and risk
      factors of respiratory diseases in farmers across Europe. A cross-sectional study
      in 7 centres was carried out. In the first stage of the study, nearly 8,000
      farmers in Denmark, Germany, Switzerland, the UK, and Spain answered a
      standardised questionnaire on farming characteristics and respiratory symptoms.
      The second stage of the study included exposure assessment and lung function
      measurements in 4 of the centres. Within the group of farmers, pig farmers were
      at high risk of asthma-like syndrome as compared to farmers keeping other kinds
      of animals. Among plant farmers, greenhouse workers were at higher risk for
      symptoms of asthma. The prevalence of symptoms of allergies were significantly
      lower among animal farmers as compared to the population of the European
      Community Respiratory Health Survey. In contrast, animal farmers had a
      significantly higher prevalence of symptoms of chronic bronchitis. The major risk
      factor for respiratory symptoms was shown to be ventilation of the animal houses
      and greenhouses. Intervention studies are now warranted to test the effectiveness
      of improved ventilation on respiratory health. The reasons for the low prevalence
      of allergic diseases among farmers are currently under study.

PMID- 12498591
TI  - Distribution of dermally absorbed 14C DDT in the organs of Wistar rats.
AB  - The aim of study was evaluation of the concentration of dermally applied (14)C
      DDT in the organs of rats, and evaluation of histological and ultrastructural
      changes after the dermal application of unlabelled DDT standard in the organs of
      rats, in which the presence of this pesticide was determined by the radio
      isotopic method. (14)C DDT of radiochemical purity of 97% was applied in the
      study. The activity of the preparation per 1 cm(2) of the tail skin was 22.2 KBq-
      (175.38 microg DDT). The material for the study was taken directly after single
      exposure and 6 h, 8 h, 10 h, 12 h, 14 h, 18 h and 20 h after exposure. The
      following organs were taken for the determination of radioactivity of tissues:
      brain, heart, lung, liver, kidney, skin at the site of exposure. Unlabelled
      chemically pure, DDT (99.7%) was used to evaluate histological and
      ultrastructural changes after dermal application. Experimental animals received
      an oil emulsion of DDT (10 mg/9 cm(2)), applied to the skin of the tail for 4
      weeks. The time of exposure was 4h daily. The animals of the control group were
      dermally exposed to the emulsion at the same time and under the same conditions.
      4 h after dermal exposure it was observed that the preparation applied on the
      surface of 9 cm(2) in the amount of 1.578 microg was present in the skin in the
      amount of 1 microg/9 cm(2) (0.11 microg/cm(2)), i.e. 0.063% of (14)C DDT applied
      dose. Directly after dermal application lasting 4 h the greatest amount of (14)C
      DDT was noted in the liver--0.285 microg, i.e. 0.033 micrcog/g. Histopatological
      and ultrastructural changes were observed in the liver, kidney, lungs and heart.

PMID- 12498592
TI  - Exposure to airborne microorganisms and endotoxin in a potato processing plant.
AB  - Microbiological air sampling was performed in a big potato processing plant
      located in eastern Poland. Air samples for determination of concentrations of
      microorganisms, dust and endotoxin were collected at 6 sites in the division
      producing potato flakes and meal from dried potato pulp and at 2 sites in the
      division producing potato syrup from imported starch. The concentrations of total
      airborne microorganisms were within a range of 28.3-93.1 x 10(3) cfu/m(3).
      Mesophilic bacteria were dominant at all sampling sites, forming 73.1-98.8% of
      the total count. Among them, distinctly prevailed corynebacteria (irregular Gram
      positive rods) that accounted for 54.3-81.1% of the total airborne microflora.
      The most common were strains of Corynebacterium spp., followed by strains of
      Arthrobacter spp., Microbacterium spp., and Agromyces ramosus. The latter
      species, so far not reported from the air of occupational environments,
      abundantly develops in the parenchyma of potato tubers. Its airborne
      concentration increased rapidly after peeling of potatoes, and attained maximal
      values at cutting and blanching (steaming and sulfuration) of potatoes, and at
      sacking of potato meal. The proportions of Gram-negative bacteria and endospore
      forming bacilli were low, respectively 0.6-7.6% and 2.0-8.1% of total count.
      Fungi constituted 1.2-26.9% of total count. The dominant species was Aspergillus
      niger that formed 99.8% of total airborne fungi. The values of the respirable
      fraction of airborne microflora varied between 25.3-73.2%. The concentrations of
      airborne dust were 1.4-26.6 mg/m(3) in the division producing potato flakes and
      meal and 114.9-200.5 mg/m(3) at pouring of potato and corn starch for syrup. The
      concentrations of airborne endotoxin were in the range of 0.011-0.089 microg/m(3)
      during the initial stages of potato processing (unloading, washing, peeling) and
      drastically increased after blanching to the extraordinarily high levels of 45.9
      1893.9 microg/m(3). At pouring of starch for syrup, the concentrations of
      airborne endotoxin were much lower, within a range of 0.029-0.156 microg/m(3). In
      conclusion, the workers of potato processing facilities could be exposed to large
      concentrations of microorganisms, dust and endotoxin posing a risk of work
      related respiratory disease.

PMID- 12498593
TI  - Precipitin response of potato processing workers to work-related microbial
      allergens.
AB  - Serum samples from 61 potato processing workers and 30 urban dwellers not exposed
      to organic dusts (as a reference group) were examined in agar-gel precipitation
      test performed by Ouchterlony double diffusion method with the antigens of 12
      microorganisms associated with organic dusts. Each serum was tested twice: not
      concentrated, and three-fold concentrated, for the detection of low levels of
      precipitins. The antibody response of workers to the antigen of coryneform
      bacterium Agromyces ramosus was high, at both not concentrated and 3-fold
      concentrated sera (respectively 29.5% and 45.9%)--significantly greater than in
      reference group (p < 0.001). Workers' response to the antigens of Gram-negative
      bacterium Alcaligenes faecalis and thermophilic actinomycete Thermoactinomyces
      vulgaris was lower (respectively 13.1% and 13.1% at not concentrated sera, 24.6%
      and 29.5% at 3-fold concentrated sera) but in all cases significantly greater
      than in reference group (p < 0.05 at not concentrated sera, p < 0.01 and p <
      0.001 at 3-fold concentrated sera). The frequency of positive precipitin
      reactions of potato workers to antigen of Penicillium citrinum was high only at 3
      fold concentrated sera (55.7%)--significantly higher compared to reference group
      (p < 0.001). The antibody response of potato workers to other antigens was either
      unspecific or low, showing no significant difference compared to reference group.
      Twenty eight out of 61 examined potato processing workers (45.9%) reported the
      occurrence of the work-related pulmonary symptoms. The frequency of positive
      precipitin reactions to Agromyces ramosus, Alcaligenes faecalis,
      Thermoactinomyces vulgaris, Penicillium citrinum and Acinetobacter calcoaceticus
      was significantly greater in the subgroup of 28 workers reporting work-related
      pulmonary symptoms compared to 33 asymptomatic workers (p < 0.05). Study results
      suggest that antigens of Agromyces ramosus, Alcaligenes faecalis,
      Thermoactinomyces vulgaris and Penicillium citrinum should be considered as
      potential occupational allergens, probably stimulating an adverse
      immunopathological reaction in the exposed potato processing workers.

PMID- 12498594
TI  - The effects of exposure to organic dust on the respiratory system of potato
      processing workers.
AB  - A cross-sectional study was carried out to evaluate lung function and the
      prevalence of work-related symptoms in workers of a potato processing plant
      located in Lublin region (eastern Poland). The study group comprised 61 workers
      employed in 2 departments. The examination included: physician-administrated
      questionnaire on occurrence of work-related symptoms, occupational history and
      smoking habits. Spirometry was performed before (7:00-8:00) and after (16:00
      17:00) the morning shift. Altogether 41/61 (67.2%) subjects reported at least one
      symptom associated with their job. Pulmonary symptoms were recorded in 28/61
      (45.9%) subjects. The most commonly recorded complaints were: cough (44.3%),
      hoarseness (19.7%), shortness of breath (18%), followed by headache and skin
      lesion (13.1% each), and eye and nose irritation (11.5%). The prevalence of work
      related symptoms (except for eye and nose irritation) was higher in the group of
      subjects working longer than 4 years (the difference was statistically
      significant only for skin lesion). Among non-smoking workers a significantly
      higher prevalence of headache was seen compared to smokers (Fisher's test, p <
      0.05). Smokers complained more frequently of respiratory symptoms such as cough,
      shortness of breath, hoarseness and chest pain. The difference was significant
      only for cough (p < 0.05). A statistically significant over-shift decline in all
      measured spirometric values: FVC, FEV(1) (p < 0.001), FEV(1)/VC (p < 0.05), PEF
      (p < 0.01) was observed.

PMID- 12498595
TI  - Occupational airborne and hand dermatitis to hop (Humulus lupulus) with non
      occupational relapses.
AB  - We report a case of a 57-years-old female farmer with occupational airborne
      dermatitis and hand dermatitis to hop (Humulus lupulus). The disease appeared at
      the age of 46, after 30 years of working with hop without any health problems.
      The patient had skin erythema of the face, neck and decollete , oedema of the
      eyelids, conjunctivitis, as well as acute dermatitis of the hands. The symptoms
      were provoked both by fresh and dried hop, appeared after half-an-hour of working
      and persisted over 1-2 days. There were no other skin or allergic problems. Skin
      tests were carried out with hop leaves (saline extract: prick positive, patch
      negative; glycerol extract: prick positive, patch negative) and hop cones (saline
      extract: prick positive, patch negative; glycerol extract: prick negative, patch
      positive after 48 and 72 hours). Despite discontinuing work, the patient
      experienced several relapses of her dermatitis. We identified new sources of hop
      allergens: a beauty cream and a herbal sedative, both containing hop extract.
      During the next hop cultivation period it also turned out that sleeping in one
      bed with her husband was provoking relapses of the patient's dermatitis. The
      husband admitted that sometimes he felt too tired to wash thoroughly after
      working on the plantation. Our case shows that connubial contacts with husband
      working in the same workplace may cause relapses of occupational dermatitis. To
      our knowledge, this is the first report on the concurrent occupational and
      connubial dermatitis to hop.

PMID- 12498596
TI  - Wild pigeons and pheasants--a source of Chlamydophila psittaci for humans and
      animals.
AB  - The authors present results of serological examination in 275 pheasants
      (Phaisanus colchicus) and 273 pigeons (Columba livia f. domestica) for the
      presence of Chlamydophila (Ch) psittaci IgG antibodies. Using micromethod of
      complement fixation (CF) test with genus-specific antigen Ch. psittaci (Bioveta,
      Ivanovice na Hane, Czech Republic), the seropositivity in pheasants oscillated
      between 31.5-40.4 %. No clinical signs of chlamydiosis were detected in pheasants
      under study. The seropositivity in pigeons ranged between 33.1-85.1%. Total 77.1%
      positivity with maximal 1:1024 antibody titre was found in 83 pigeons caught in
      April 2000, while, in June 2000 positivity was 41.0% with maximum titre 1: 512.
      Similarly, in the year 2001 the seropositivity in the group of 74 pigeons trapped
      in April reached up to 85.1% with the highest titre 1:1024 and in the pigeons
      trapped in June positivity decreased to 33.3% with the titer 1:256. These results
      prove an acute form of chlamydiosis and suggest that pigeons in spring time are
      an especially significant source of chlamydiosis for the human and animal
      population.

PMID- 12498597
TI  - Positive findings of Borrelia burgdorferi in Culex (Culex) pipiens pipiens larvae
      in the surrounding of Brno city determined by the PCR method.
AB  - After first finding Borrelia in the midgut of imago mosquitoes, we concentrated
      on the presence of Borrelia in mosquito development stages--larvae of the third
      or fourth instar. In the summer season in the years of 2000-2001 a total of 439
      Culex (Culex) pipiens pipiens larvae were collected from a barrel of rainwater in
      the Obrany holiday area of Brno city (East Moravia, Czech Republic). The larvae
      midgut was observed under dark-field microscopy. Ten DFM positive samples (2.28%)
      were further analysed using the single-tube nested PCR method for the presence of
      flagellum DNA sequence specific for Borrelia burgdorferi sensu lato, of which 5
      were positive. Borrelian positivity of Culex (C.) pipiens pipiens larvae was
      1.14%. One spirochete isolated strain in BSK-H medium was obtained. PCR detection
      for borrelian DNA of the isolated strain was negative. From these results we can
      conclude that a low percentage Borreliae can be also found in mosquito larvae and
      are likely to survive into imago stage.

PMID- 12498598
TI  - Legionella in sprinkling water as a potential occupational risk factor for
      gardeners.
AB  - To study a possibility of infection with Legionella at gardening by inhaling of
      water aerosolized at sprinkling of plants, samples of tap water used for
      sprinkling of plants grown in outdoor gardens and in greenhouses in the Lublin
      province (eastern Poland) were examined for the presence of Legionella, along
      with the samples of soil, artificial medium and air collected in modern
      greenhouses. The strains of Legionella were isolated from 8 out of 36 samples of
      water (22.2%) collected from outdoor taps used for sprinkling plants cultivated
      in outdoor gardens, and from 5 out of 20 samples of water (25.0%) collected from
      indoor taps used for sprinkling of plants cultivated in traditional greenhouses
      or foil tunnels. Both in the samples collected from outdoor and indoor taps
      Legionella pneumophila 2-14 was more common than Legionella spp. (respectively
      13.9% vs. 8.3%, and 15.0% vs. 10.0%). No legionellae were found in 18 samples of
      tap water, 14 samples of soil, 14 samples of artificial medium or 6 samples of
      air collected in modern greenhouses. The results of this preliminary study
      suggest that water aerosolized at sprinkling of plants represents a potential
      source of Legionella infection among gardeners.

PMID- 12498599
TI  - Position of the hyoid bone in cleft lip, alveolus, and palate: variation of
      normal anatomy or sign accompanying the malformation?
AB  - OBJECTIVE: To compare the hyoid bone position in patients with clefts of lip,
      alveolus, and palate with orthodontic patients with no cleft. DESIGN:
      Retrospective cephalometric long-term study. PATIENTS: Lateral cephalograms of 23
      patients with a complete unilateral cleft were compared with those of 24
      orthodontic patients with no cleft with an Angle class 1 occlusion. Twenty-five
      of the patients were girls, and 22 were boys. The age of the patients with cleft
      at the beginning of the study was 8.1 +/- 0.7 years and at the end 14.8 +/- 0.6
      years. The patients without cleft were 8.4 +/- 0.8 years old at the beginning and
      14.4 +/- 0.6 years at the end of the study. MAIN OUTCOME MEASURES: Cephalometric
      analysis was used to determine the skull growth pattern as well as the positions
      of the head and hyoid bone twice in all 47 persons. RESULTS: With increasing age
      of the patients, the skull growth pattern changed from vertical to horizontal
      growth, but no significant differences were found between patients with and
      without cleft. Head position did not differ significantly between patients with
      and without cleft. However, hyoid bone position differed significantly. The hyoid
      in patients with cleft was located more caudally and more anteriorly than in
      patients without cleft. CONCLUSION: The hyoid bone in a subset of north German
      adolescents with complete unilateral cleft lip and palate was found to be caudal
      and anterior, compared with a control group.

PMID- 12498600
TI  - Volume and shape of masticatory muscles in patients with hemifacial microsomia.
AB  - OBJECTIVE: To test the following hypotheses in hemifacial microsomia (HFM): (1)
      the volumes of the masseter, lateral and medial pterygoid, and temporal muscles
      are reduced on the affected versus unaffected side; (2) significant differences
      exist between the degrees of right-left disproportion in these four masticatory
      muscles; (3) circumferential shapes of the masticatory muscles are more irregular
      on the affected versus unaffected side; and (4) the degree of masticatory muscle
      right-left disproportion can be judged by the degree of ear, mandibular, or
      dental anomalies. SUBJECTS AND METHODS: Ten preadolescent patients with HFM were
      studied using facial photographs, dental casts, cephalometric and panoramic
      radiographs, and helical computed tomography scanning and three-dimensional
      reconstruction technique. Volumes of masseter, lateral and medial pterygoid, and
      temporal muscles on both sides were measured. Muscle volume disproportion was
      expressed as the affected/unaffected ratio. Muscle circumferential irregularity
      was expressed as the ratio between the total circumferential length and
      corresponding cross-sectional area. RESULTS: Masticatory muscle volumes were
      significantly smaller on the affected versus unaffected side. No significant
      differences were observed between the degrees of disproportion of the four
      masticatory muscles examined. Circumferential shapes of masticatory muscles were
      significantly more irregular on the affected versus unaffected side. There were
      no significant relationships of the degree of ear, mandibular, or dental
      anomalies in relation to masticatory muscle disproportion. CONCLUSIONS: In HFM
      the masseter, lateral and medial pterygoid, and temporal muscles all have a
      significantly smaller volume on the affected versus unaffected side, and specific
      muscles were not severely affected in the present subjects. Furthermore, all four
      muscles showed a significantly more irregular shape on the affected versus
      unaffected side. Finally, the severity of masticatory muscle disproportion can
      probably not be judged by the degree of ear, mandibular, and dental anomalies in
      preadolescent patients with HFM.

PMID- 12498601
TI  - Surgical airway management in Pierre Robin sequence: is there a role for tongue
      lip adhesion?
AB  - OBJECTIVE: The purpose of this study was to examine the efficacy of tongue-lip
      adhesion (TLA) in the management of clinically significant airway obstruction
      associated with Pierre Robin sequence. DESIGN: The records of all children
      admitted to The Children's Hospital of Philadelphia with a diagnosis of Pierre
      Robin sequence were reviewed. Charts were reviewed for birth data, diagnosis,
      preoperative airway management methods, and surgical intervention. Records of
      infants undergoing TLA were analyzed for timing of surgery, operative technique,
      postoperative complications, length of hospital stay, and treatment outcome.
      RESULTS: Over the 28-year period 1971 to 1999, 107 patients (47 boys, 60 girls)
      meeting the criteria for Pierre Robin sequence were admitted for treatment. Of
      these, 74 (69.2%) were successfully managed by positioning alone. Surgical
      management of the airway was performed in the remaining 33 (30.8%) patients, 29
      of whom underwent TLA and 4 of whom underwent tracheostomy. Dehiscence of the
      adhesion occurred in five patients (17.2%), two of whom subsequently required
      tracheostomy. Within the group of patients who underwent mucosal adhesion alone,
      the dehiscence rate was 41.6%. When the adhesion included muscular sutures,
      however, dehiscence was not observed in any patient. Of the 24 patients in whom
      primary TLA healed uneventfully, airway obstruction was successfully relieved in
      20 (83.3%). Failure of a healed TLA to relieve the airway obstruction resulted in
      conversion to a tracheostomy in four patients. Six patients who underwent TLA
      (20.7%) ultimately required a tracheostomy; five of these patients (83.3%) were
      syndromic. Of patients requiring preoperative intubation, 42.9% ultimately
      required tracheostomy. CONCLUSION: TLA successfully relieves airway obstruction
      that is unresponsive to positioning alone in the majority of patients with Pierre
      Robin sequence and should therefore play an important role in the management of
      these infants.

PMID- 12498602
TI  - Speech development of children with cleft palate before and after palatal
      surgery.
AB  - OBJECTIVE: This study examined the speech production abilities of children with
      cleft palate before and after palate repair. PARTICIPANTS: Twenty-eight children
      participated in the study, 14 with cleft palate and 14 without clefts matched for
      age, gender, and mothers' educational level. MAIN OUTCOME MEASURES: Comparisons
      were made between the children with cleft palate before and after surgery for
      canonical babbling ratios, size of consonant inventories, place and manner
      characteristics, and early developing sounds [p, b, t, d, k, g, m, n, eta]. Also,
      comparisons were made between the children with cleft palate and their peers
      without clefts at postsurgery/17 months for the measures described above.
      RESULTS: Paired t tests revealed differences in pre- and postsurgery performance
      of the children with cleft palate for production of canonical syllables and size
      of consonant inventories. Although no significant differences were noted for
      place and manner features, production of oral stops doubled from the time before
      surgery to that after surgery. Specifically, production of the bilabial stop [b]
      showed significant change over time. Results of independent t tests indicated no
      difference between groups for production of canonical syllables and size of
      consonant inventories at 17 months. However, significant group differences were
      noted for production of stops, oral stops, nasals, glides, and alveolars. The
      children without clefts produced more stops, oral stops, and alveolars. In
      contrast, more nasals and glides were seen in the vocalizations of the children
      with cleft palate. CONCLUSIONS: Children with cleft palate made gains in
      production of canonical syllables and size of consonant inventories postsurgery;
      however, they continued to show deficits in production of stops and alveolar
      place features.

PMID- 12498603
TI  - Phonological development of toddlers with unilateral cleft lip and palate who
      were treated with and without infant orthopedics: a randomized clinical trial.
AB  - OBJECTIVE: To investigate the phonological development of toddlers from 2 to 3
      years of age with complete unilateral cleft lip and palate (UCLP) treated during
      the first year of life with and without infant orthopedics (IO). DESIGN: In a
      randomized clinical trial (Dutchcleft), two groups of children were followed up:
      one treated with IO (IO group) and another that did not receive IO (non-IO
      group). Phonological skills were analyzed at 2, 2.5, and 3 years of age using a
      system for assessing phonological development of Dutch children (Fonologische
      Analyse van het Nederlands: FAN). The analysis included number of acquired
      consonants, order of phonological development, use of phonological processes, and
      occurrence of nasal escape. PATIENTS: Criteria for inclusion were complete UCLP,
      no soft tissue bands, no other malformations, parents fluent in Dutch, birth
      weight of a minimum of 2500 g, and gestation time of a minimum of 38 weeks.
      INTERVENTIONS: IO treatment based on a modified Zurich approach was started
      within 2 weeks after birth and used until soft palate closure at 12 months of
      age. Children in the non-IO group visited the clinic for an extra check-up at 6
      weeks as well as before and after lip repair and soft palate closure. All other
      interventions were the same across groups. RESULTS: Phonological development of
      most 2.5-year-old IO children was normal or delayed. Most children in the non-IO
      group followed an abnormal developmental pattern. At age 3, the children in the
      IO group had acquired more initial consonants. There were no group differences in
      the use of phonological processes or the occurrence of nasal escape. CONCLUSIONS:
      Children treated with IO during their first year of life followed a more normal
      path of phonological development between 2 and 3 years of age.

PMID- 12498604
TI  - Comparison of nasalance scores obtained from the Nasometer and the NasalView.
AB  - OBJECTIVE: Nasalance scores obtained from the Nasometer and the NasalView were
      compared for five different sentences. DESIGN: Vowel content was controlled in
      the design of the five stimulus sentences. One sentence was loaded with high
      front vowels, one with high-back vowels, one with low-front vowels, one with low
      back vowels, and one contained a mixture of vowel types. SUBJECTS: The subjects
      were 50 elementary school children ranging from kindergarten to sixth grade. Each
      subject was a native speaker of English, had no history of adenoidectomy, and was
      not currently enrolled in speech therapy services. MAIN OUTCOME MEASURES: The
      main outcome measures were the nasalance scores obtained from the Nasometer and
      the NasalView for each of the five sentences. RESULTS: There was a significant
      difference in the nasalance scores between the Nasometer and the NasalView for
      four of the five stimuli, but not all differences were in the same direction. For
      two stimuli, the Nasometer scores were significantly higher, and for two stimuli
      the NasalView scores were higher. Bivariate correlations between nasalance scores
      for individual stimuli were in the good range for the Nasometer but poor for the
      NasalView. CONCLUSION: Speech stimuli weighted with different vowel types are
      differentially affected by the different acoustical filtering used in the
      Nasometer versus the NasalView. Nasalance scores obtained with the NasalView were
      qualitatively and quantitatively different from those obtained with the
      Nasometer. This suggests that the two machines provide different information, and
      the scores are not interchangeable.

PMID- 12498605
TI  - Aerodynamic and cephalometric analyses of velopharyngeal structure and function
      following re-pushback surgery for secondary correction in cleft palate.
AB  - OBJECTIVE: The goal of this study was to clarify the efficacy of and indication
      for re-pushback surgery as secondary treatment for cleft palate. PARTICIPANTS:
      Fifteen patients treated by re-pushback surgery involving intravelar veloplasty
      (IVV) with buccal mucosal grafting on the nasal surface and followed up more than
      6 months were enrolled in this study. MAIN OUTCOME MEASURES: Pre- and
      postoperative velopharyngeal functions were analyzed by perceptual voice
      analysis, blowing ratio, and nasalance scores during phonation of /i/ and /tsu/.
      Cephalometric analysis was used to evaluate the relationship between
      velopharyngeal structure and the outcome of re-pushback surgery. Control data
      were obtained from the longitudinal files of normal 10-year-old children in
      Kyushu University Dental Hospital. RESULTS: Eight of 15 patients obtained
      complete velopharyngeal closure (complete group), five patients improved
      remarkably (improved group), and no effective result was seen in two patients
      (ineffective group). Nasality disappeared or remarkably improved after the
      operation in 13 patients. Effective surgical results were found in 86.7% of the
      patients. Partial flap necrosis was seen in two patients in whom re-pushback
      surgery was performed using mucosal palatal flaps instead of mucoperiosteal
      flaps. Preoperative velar length and the length/depth ratio of the re-pushback
      group were significantly smaller than the controls, but there was no difference
      after the operation. Furthermore, the preoperative length/depth ratio of the
      complete group (ranged more than 100%) was significantly greater than those of
      the other two groups (ranged less than 100%). CONCLUSION: Re-pushback surgery by
      IVV with free mucous grafting on the nasal surface was effective in managing
      velopharyngeal incompetence secondarily, improving velopharyngeal structure and
      function.

PMID- 12498606
TI  - Effects of orthognathic surgery on speech and breathing of subjects with cleft
      lip and palate: acoustic and aerodynamic assessment.
AB  - OBJECTIVE: To evaluate the impact of orthognathic surgery on acoustic nasalance
      of subjects with cleft and investigate the causes of possible changes by
      analyzing velopharyngeal function and nasal patency. DESIGN/PATIENTS: Nasalance
      was measured in 29 subjects with operated cleft palate +/- lip before (PRE) and
      45 days (POST1) and 9 months (POST2) after surgery, on average. In 19 of the
      patients, the minimum velopharyngeal (VP) and nasal cross-sectional (N) areas
      were also determined. INTERVENTIONS: Le Fort I osteotomy with maxillary
      advancement in combination with procedures involving the nose, maxilla, mandible
      or all three. MAIN OUTCOME MEASURES: Nasalance, VP area, N area. RESULTS: We
      observed: (1) a significant (p < .05) increase in mean nasalance at POST1 and
      POST2, compared with PRE during the reading of oral sentences and nasal
      sentences; at POST2, high nasalance on the oral sentences was observed in 45% of
      the patients with normal nasalance at PRE, and 57% of patients with low nasalance
      on the nasal sentences at PRE no longer presented abnormal nasalance; (2) a
      significant increase in mean VP area at POST1; two borderline patients
      demonstrated deterioration of VP closure at POST2, compared with PRE; and (3) a
      significant increase in mean N area at POST2, with 73% of patients no longer
      presenting subnormal areas seen at PRE. CONCLUSIONS: On a long-term basis,
      orthognathic surgery modifies speech nasalance of some subjects with cleft,
      perhaps because of an increase in internal nose size. This may also improve nasal
      patency for breathing.

PMID- 12498607
TI  - Importance of soft tissue for skeletal stability in maxillary advancement in
      patients with cleft lip and palate.
AB  - OBJECTIVE: Assessment of stability of the advanced maxilla after two-jaw surgery
      and Le Fort I osteotomy in patients with cleft palate based on soft tissue
      planning. SUBJECTS: Between 1995 and 1998, 15 patients with cleft lip and palate
      deformities underwent advancement of a retruded maxilla, without insertion of
      additional bone grafts. Eleven patients had bimaxillary osteotomies and four
      patients only a Le Fort I osteotomy. Relapse of the maxilla in horizontal and
      vertical dimensions was evaluated by cephalometric analysis after a clinical
      follow-up of at least 2 years. RESULTS: In the bimaxillary osteotomies,
      horizontal advancement was an average 4 mm at point A. After 2 years, there was
      an additional advancement of point A of an average of 0.7 mm. In the mandible, a
      relapse of 0.8 mm was seen after an average setback of 3.9 mm. In the four
      patients with Le Fort I osteotomy, point A was advanced by 3.8 mm and the relapse
      after 2 years was 0.9 mm. Vertical elongation at point A resulted in relapse in
      both groups. Impaction of the maxilla led to further impaction as well.
      CONCLUSION: Cephalometric soft tissue analysis demonstrates the need for a two
      jaw surgery, not only in severe maxillary hypoplasia. Alteration of soft tissue
      to functional harmony and three-dimensional correction of the maxillomandibular
      complex are easier to perform in a two-jaw procedure. It results in a more stable
      horizontal skeletal position of the maxilla.

PMID- 12498608
TI  - Chromosome 17: gene mapping studies of cleft lip with or without cleft palate in
      Chinese families.
AB  - OBJECTIVE: Involvement of loci on chromosome 17, including retinoic acid receptor
      alpha (RARA) in nonsyndromic oral clefts has been reported in Caucasian
      populations, although never investigated in Asian populations. The purpose of the
      present study was to investigate several loci on chromosome 17, including RARA,
      in Chinese families. PARTICIPANTS: Thirty-six multiplex families (310
      individuals), ascertained through nonsyndromic cleft lip with or without cleft
      palate surgical probands from hospitals in Shanghai, China, participated in the
      present study. There were 23 families whose probands had cleft lip and cleft
      palate (CLP) and 13 with cleft lip alone (CL). RESULTS: Seventeen markers,
      spanning chromosome 17 and about 10 cM apart were assessed. Logarithm of odds
      ratio (LOD) scores (two point and multipoint), model-free linkage analyses, and
      allelic association tests (transmission/disequilibrium, Fisher's exact tests, and
      chi-square) were performed on the total family sample, families with CLP probands
      (CLP subgroup), and families with CL probands (CL subgroup). LOD scores from the
      two-point analyses were inconclusive. Multipoint analyses rejected linkage except
      for a few regions in the CL subgroup. However, positive results were found using
      the model-free linkage and association methods (p < .05). The markers with
      positive results varied across the CL and CLP subgroups. However, the RARA region
      and loci nearby yielded consistently positive results. CONCLUSION: Genetic
      variation within the RARA locus or nearby appears to be involved in the
      pathogenesis of nonsyndromic oral clefts in this population. Furthermore, based
      on the differing pattern of results in the CL versus CLP subgroups, it appears
      that the formation of CL and CLP is because of either differing alleles at the
      same genetic locus or different but related (and/or linked) genes that modify the
      severity and expression of oral clefting.

PMID- 12498609
TI  - A survey of cleft lip and palate management taught in training programs in Korea.
AB  - OBJECTIVE: A national survey was conducted to obtain an overall view of the
      status, assess changes in trends of cleft management, and study new categories of
      interest. METHOD: Questionnaires were sent to 90 chief residents of all Korean
      institutes with plastic surgery training programs. RESULTS: Forty-eight
      respondents returned completed questionnaires. The results were: (1) the most
      common unilateral cleft lip repair method used is the rotation-advancement
      technique (100%); (2) 73% of respondents correct cleft lip nasal deformity at
      preschool age; (3) the Millard technique is the most common management in
      bilateral cleft lip repair (65%); (4) in the management of protruding premaxilla,
      44% of the respondents choose presurgical orthopedics; (5) the usual cleft palate
      repairs are the pushback (64%) and double-opposing Z-plasty (43%) in complete
      cleft palates and the double-opposing Z-plasty (75%) and pushback (36%) comprised
      the common techniques in incomplete cases; (6) 86% of responding programs perform
      alveolar cleft repairs during the period of mixed dentition; the most common
      treatment of velopharyngeal incompetence is pharyngeal flap (71%); and (8) the
      interdisciplinary team approach is practiced by 64% of respondents. CONCLUSIONS:
      Many changes were noted since a previous 1995 survey. We hope that this study
      provides the necessary information needed for the eventual establishment of
      standard cleft management in Korea.

PMID- 12498610
TI  - Breast-feeding and sugar intake in babies with cleft lip and palate.
AB  - OBJECTIVE: To investigate the pattern of breast-feeding and sugar intake among
      babies with cleft lip and palate. PARTICIPANTS: Caretakers of 200 babies with
      cleft lip and palate enrolled at the Hospital for Rehabilitation of Craniofacial
      Anomalies, University of Sao Paulo, Bauru, Brazil. RESULTS: A low prevalence of
      breast-feeding was found. The most reported reason was the sucking inability of
      the baby. Complete cleft lip and palate was the primary cause affecting sucking.
      The first contact with sugar occurred mainly through the baby bottle with milk
      during the first month of life. For nutritional supplement, the children were
      given sugar and fruit juices in the bottle. CONCLUSIONS: It was observed that
      dietary habits in babies with cleft lip and palate are more risky. This
      highlights the role played by early education and constant oral hygiene follow-up
      for prevention in these patients.

PMID- 12498611
TI  - Case report: cleft palate closure in 18-month-old female with epidermolysis
      bullosa.
AB  - OBJECTIVE: In a patient with epidermolysis bullosa and cleft palate,
      perioperative guidelines and surgical management can be unclear. This case report
      illustrates the occurrence of a skin anomaly often associated with potentially
      significant morbidity and a cleft palate. Perioperative guidelines to
      successfully manage the cleft palate closure in these patients are presented.

PMID- 12498612
TI  - Bilateral superiorly based full-thickness nasolabial island flaps for closure of
      residual anterior palatal fistulas in an unoperated elderly patient.
AB  - OBJECTIVE: Unoperated bilateral complete cleft lip and palate in an adult or
      elderly patient is seen rarely, and the existence of unoperated clefts is a
      result of unfavorable economic and social circumstances. We report an unoperated
      65-year-old patient with bilateral complete cleft lip and palate and present our
      preference for the surgical management. INTERVENTIONS: Repair of the bilateral
      complete cleft lip and palate was successfully carried out using straight-line
      closure for the bilateral cleft lip and two-flap pushback palatoplasty with
      superiorly based lateral port control pharyngeal flap for the wide cleft palate
      at the first stage, and large residual anterior palatal fistulas were closed
      using bilateral superiorly based (retrograde flow) full-thickness nasolabial
      island flaps at the second stage. CONCLUSIONS: To our knowledge based on a review
      of the literature, this is the first report of an elderly patient with bilateral
      complete cleft lip and palate and the first application of bilateral superiorly
      based (retrograde flow) full-thickness nasolabial island flaps for closure of
      large residual anterior palatal fistulas or alveolar clefts. The bilateral
      superiorly based (retrograde flow) full-thickness nasolabial island flap may be a
      good solution in large anterior palatal defects using unilaterally or bilaterally
      in a single stage with minimal donor site morbidity, in which there is not enough
      tissue for local repair or if previous attempts are unsuccessful.

PMID- 12498613
TI  - Midface distraction to alleviate upper airway obstruction in achondroplastic
      dwarfs.
AB  - OBJECTIVE: The use of midface distraction in patients with achondroplasia and
      upper airway obstruction secondary to midface hypoplasia has not been reported.
      In this report, we review the treatment of two patients with severe midface
      hypoplasia and obstructive sleep apnea secondary to achondroplasia using midface
      distraction osteogenesis. DESIGN, SETTING, AND PATIENTS: Two patients with
      achondroplastic dwarfism and midface hypoplasia with airway obstruction were
      treated in a tertiary referral center for craniofacial disorders. RESULTS AND
      CONCLUSIONS: Both patients had their tracheostomies decannulated after midface
      distraction of 25 mm. Midface distraction osteogenesis is useful to alleviate
      upper airway obstruction from midface hypoplasia seen in achondroplasia.

PMID- 12498614
TI  - Syngnathia and Van der Woude syndrome: a case report and literature review.
AB  - OBJECTIVE: Syngnathia is a rare anomaly involving soft tissue or bony adhesions
      between the maxilla and mandible. We review the literature and present a case of
      syngnathia associated with Van der Woude syndrome. Syngnathia can have very
      different etiologies, but this has rarely been reported in Van der Woude
      syndrome. Treatment of this condition is rarely discussed in the literature
      because of a paucity of case reports. RESULTS: Oral adhesion (syngnathia) in our
      patient was caused by a mandibular to maxillary fibrous band. Surgical treatment
      was successful. Clinical implications and review of literature for the treatment
      of this rare association of syngnathia and Van der Woude syndrome are discussed.

PMID- 12498615
TI  - Palate re-repair revisited.

PMID- 12498617
TI  - Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid
      esters.
AB  - BACKGROUND: Sarcoidosis is a multisystem disease of unknown origin characterized
      by the formation of noncaseating granulomas, in particular in the lungs, lymph
      nodes, eyes, and skin. Systemic treatment for cutaneous sarcoidosis can be used
      for large disfiguring lesions, generalized involvement, or recalcitrant lesions
      that did not respond to topical therapy. CASE PRESENTATIONS: We report three
      patients with recalcitrant cutaneous sarcoidosis who were treated with oral
      fumaric acid esters (FAE). Three female patients presented with cutaneous
      sarcoidosis that have proved to be refractory to various therapies, including
      corticosteroids and chloroquine. We treated the patients with FAE in tablet form
      using two formulations differing in strength (Fumaderm initial, Fumaderm). Dosage
      of FAE was performed according to the standard therapy regimen for psoriasis
      patients. After treatment with FAE (4-12 months), a complete clearance of skin
      lesions was achieved in the three patients. The side effects observed in this
      trial correspond to the well-known spectrum of adverse effects of FAE (flush,
      minor gastrointestinal complaints, lymphopenia). CONCLUSIONS: On the basis of our
      findings FAE therapy seems to be a safe and effective regimen for patients with
      recalcitrant cutaneous sarcoidosis. Nevertheless further investigations are
      necessary to confirm our preliminary results.

PMID- 12498618
TI  - Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of
      chronic fatigue syndrome and non-fatigued subjects.
AB  - BACKGROUND: The association of an infectious agent with chronic fatigue syndrome
      (CFS) has been difficult and is further complicated by the lack of a known lesion
      or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection
      and disease occurring throughout the body. This type of systemic sample coupled
      with broad-range amplification of bacterial sequences was used to determine
      whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS and
      55 non-fatigued subjects was assessed to determine plasma DNA concentration and
      the presence of bacterial 16S ribosomal DNA (rDNA) sequences. RESULTS: DNA was
      isolated from 81 (91%) of 89 plasma samples. The 55 non-fatigued subjects had
      higher plasma DNA concentrations than those with CFS (average 151 versus 91 ng)
      and more CFS subjects (6/34, 18%) had no detectable plasma DNA than non-fatigued
      subjects (2/55, 4%), but these differences were not significant. Bacterial
      sequences were detected in 23 (26%) of 89. Only 4 (14%) CFS subjects had 16S rDNA
      sequences amplified from plasma compared with 17 (32%) of the non-fatigued (P =
      0.03). All but 1 of the 23 16S rDNA amplicon-positive subjects had five or more
      unique sequences present. CONCLUSIONS: CFS subjects had slightly lower
      concentrations or no detectable plasma DNA than non-fatigued subjects. There was
      a diverse array of 16S rDNA sequences in plasma DNA from both CFS and non
      fatigued subjects. There were no unique, previously uncharacterized or
      predominant 16S rDNA sequences in either CFS or non-fatigued subjects.

PMID- 12498619
TI  - Cynomolgus monkey testicular cDNAs for discovery of novel human genes in the
      human genome sequence.
AB  - BACKGROUND: In order to contribute to the establishment of a complete map of
      transcribed regions of the human genome, we constructed a testicular cDNA library
      for the cynomolgus monkey, and attempted to find novel transcripts for
      identification of their human homologues. RESULT: The full-insert sequences of
      512 cDNA clones were determined. Ultimately we found 302 non-redundant cDNAs
      carrying open reading frames of 300 bp-length or longer. Among them, 89 cDNAs
      were found not to be annotated previously in the Ensembl human database. After
      searching against the Ensembl mouse database, we also found 69 putative coding
      sequences have no homologous cDNAs in the annotated human and mouse genome
      sequences in Ensembl. We subsequently designed a DNA microarray including 396 non
      redundant cDNAs (with and without open reading frames) to examine the expression
      of the full-sequenced genes. With the testicular probe and a mixture of probes of
      10 other tissues, 316 of 332 effective spots showed intense hybridized signals
      and 75 cDNAs were shown to be expressed very highly in the cynomolgus monkey
      testis, but not ubiquitously. CONCLUSIONS: In this report, we determined 302 full
      insert sequences of cynomolgus monkey cDNAs with enough length of open reading
      frames to discover novel transcripts as human homologues. Among 302 cDNA
      sequences, human homologues of 89 cDNAs have not been predicted in the annotated
      human genome sequence in the Ensembl. Additionally, we identified 75 dominantly
      expressed genes in testis among the full-sequenced clones by using a DNA
      microarray. Our cDNA clones and analytical results will be valuable resources for
      future functional genomic studies.

PMID- 12498620
TI  - The temporal reliability of serum estrogens, progesterone, gonadotropins, SHBG
      and urinary estrogen and progesterone metabolites in premenopausal women.
AB  - BACKGROUND: There is little existing research to guide researchers in estimating
      the minimum number of measurement occasions required to obtain reliable estimates
      of serum estrogens, progesterone, gonadotropins, sex hormone-binding globulin
      (SHBG), and urinary estrogen and progesterone metabolites in premenopausal women.
      METHODS: Using data from a longitudinal study of 34 women with a mean age of 42.3
      years (SD = 2.6), we calculated the minimum number of measurement occasions
      required to obtain reliable estimates of 12 analytes (8 in blood, 4 in urine).
      Five samples were obtained over 1 year: at baseline, and after 1, 3, 6, and 12
      months. We also calculated the percent of true variance accounted for by a single
      measurement and intraclass correlation coefficients (ICC) between measurement
      occasions. RESULTS: Only 2 of the 12 analytes we examined, SHBG and estrone
      sulfate (E1S), could be adequately estimated by a single measurement using a
      minimum reliability standard of having the potential to account for 64% of true
      variance. Other analytes required from 2 to 12 occasions to account for 81% of
      the true variance, and 2 to 5 occasions to account for 64% of true variance. ICCs
      ranged from 0.33 for estradiol (E2) to 0.88 for SHBG. Percent of true variance
      accounted for by single measurements ranged from 29% for luteinizing hormone (LH)
      to 92% for SHBG. CONCLUSIONS: Experimental designs that take the natural
      variability of these analytes into account by obtaining measurements on a
      sufficient number of occasions will be rewarded with increased power and
      accuracy.

PMID- 12498622
TI  - Recommendations by health organizations for pulse consumption.
AB  - The present paper aims to study why and how health organizations recommend the
      consumption of pulses such as beans, chickpeas or lentils. Although it is
      recognized that frequent pulse consumption may reduce serum cholesterol levels
      and helps reduce risks of coronary heart disease and diabetes, these advantages
      are scarcely mentioned by health-promoting associations, i.e. vegetarians and
      organizations helping people to reduce the risks for chronic diseases. Pulses,
      especially common beans, are rather considered as whole grains that provide
      plenty of proteins, starch, dietary fibres, minerals and vitamins. Many
      organizations refer to the food guide pyramid to advise their members, and place
      beans either in the third part, together with meat, in the second one with fruits
      and vegetables, or in the bottom part with starchy foods. Whatever their place,
      they have acquired the status of staple food for anyone who wants to eat a
      healthy diet.

PMID- 12498623
TI  - Overview of the market and consumption of pulses in Europe.
AB  - The human consumption of grain legumes and pulses in Europe and the EU is lower
      than in other regions of the world. However, there is a lot of variation between
      countries and an overall slight increase has been observed in recent years. The
      major trends in the EU pulse market are illustrated here with a specific focus on
      Spain, France and the UK, which account for about 60 % of the EU pulse
      consumption. The ways in which pulses are consumed are very different in the
      various EU countries, due to different regional food habits and traditions, and
      to differences in the supplies of grain legumes and the markets. Canned products
      dominate pulse sales compared with dry pulses sold in packets. Dry beans are the
      most consumed of the pulses in the EU, but the preference between species varies
      according to country. The factors limiting the consumption of pulses in the EU
      are mainly: an inadequate level of innovation for developing products adapted to
      modern life, a small home supply of pulses and competition from cheaper low
      quality imports. Recently, however, consumers are favouring healthy and balanced
      vegetable diets. Pulses have significant nutritional and health advantages for
      consumers and their cultivation has a positive impact on agriculture and the
      environment. Therefore the trend in the consumption of pulses could change,
      especially if publicity about the benefits of pulses is improved and if the food
      industry and professional organizations take up the challenge to incorporate
      grain legumes in novel, convenient and healthy food products.

PMID- 12498624
TI  - Factors influencing pulse consumption in Latin America.
AB  - In Latin America, pulse consumption ranges from 1 kg/capita per year (Argentina)
      to 25 kg/capita per year (Nicaragua). Common beans account for 87 % of the total.
      The differences between countries, regions or groups of population within the
      same country can be explained by the following factors: (1) beans are very
      nutritious; (2) beans and maize are traditional foods and the habit of consuming
      them is deeply rooted in many people and communities; (3) the rural population
      eats more pulses than the urban population, due to geographical constraints that
      limit exchanges and favour consumption of locally produced foods; (4) income
      level, beans are still the poor man's meat; and (5) other factors, such as
      consumers' taste, the constraints on cooking beans, etc. The evolution of the
      consumption level in the future will depend on the urbanization of the
      population, access to processed foods and income level. Health issues would be an
      argument for maintaining or increasing the current consumption level.

PMID- 12498625
TI  - Health benefits of low glycaemic index foods, such as pulses, in diabetic
      patients and healthy individuals.
AB  - The present paper covers the health benefits of low glycaemic index foods, such
      as pulses. Nutritional factors potentially play a crucial role in health and
      disease. A low-fat, high-carbohydrate diet is often recommended as a part of a
      healthy life-style. Historical works have shown that carbohydrate foods differ in
      their ability to affect post-ingestive glycaemia. The glycaemic index concept
      allows a ranking of carbohydrate-rich foods in terms of their blood glucose
      raising potential. Pulses are foods with very low glycaemic index values.
      Numerous studies have documented the health benefits that can be obtained by
      selecting foods of low glycaemic index. These benefits are of crucial importance
      in the dietary treatment of diabetes mellitus: glycaemic control is improved as
      well as several metabolic parameters, such as blood lipids. The results of human
      studies have been confirmed by animal experiments in the field of diabetes. Diets
      with low glycaemic index value improve the prevention of coronary heart disease
      in diabetic and healthy subjects. In obese or overweight individuals, low
      glycaemic index meals increase satiety and facilitate the control of food intake.
      Selecting low glycaemic index foods has also demonstrated benefits for healthy
      persons in terms of post-prandial glucose and lipid metabolism. Several public
      health organizations have recently integrated consideration of the glycaemic
      index in their nutritional recommendations for patients with metabolic diseases
      and for the general population.

PMID- 12498626
TI  - Pulses and lipaemia, short- and long-term effect: potential in the prevention of
      cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the leading cause of death in most developed
      countries. Most CVD deaths are preventable through life-style measures such as
      diet, exercise and avoidance of cigarette smoking. Decreased intake of saturated
      fat and cholesterol and increased intake of cholesterol-reducing foods, such as
      pulses, deserve a high priority for activities designed to prevent CVD.
      Epidemiological and observational studies indicate that habitual intakes of large
      amounts of dietary fibre or of vegetables are associated with significantly lower
      rates of CVD. Studies over four decades document the hypocholesterolaemic effect
      of pulses and soyabeans. We performed a meta-analysis of eleven clinical trials
      that examined the effects of pulses (not including soyabeans) on serum
      lipoproteins. Intake of non-soya pulses was associated with these changes:
      fasting serum cholesterol, -7.2 %, 95 % CI -5.8, -8.6 %; LDL-cholesterol, -6.2 %,
      95 % CI -2.8, -9.5 %; HDL-cholesterol, +2.6 %, 95 % CI +6.3, -1.0 %;
      triacylglycerols, -16.6 %, 95 % CI -11.8 %, -21.5 %; and body weight, -0.9 %, 95
      % CI +2.2 %, -4.1 %. The hypocholesterolaemic effects of pulses appear related,
      in estimated order of importance, to these factors: soluble dietary fibre,
      vegetable protein, oligosaccharides, isoflavones, phospholipids and fatty acids,
      saponins and other factors. Intake of pulses may also reduce risk for CVD by
      favourable effects on blood pressure, glycaemia and risk for diabetes, and risk
      for obesity. Overall, the available evidence indicates that regular consumption
      of pulses may have important protective effects on risk for CVD.

PMID- 12498627
TI  - Pulses and carcinogenesis: potential for the prevention of colon, breast and
      other cancers.
AB  - Consumption of pulses as components of healthy diets is encouraged because it is
      believed that this is likely to help in reducing the risk of common non
      communicable diseases, including cancers. However, the evidence base for the role
      of pulses in prevention of cancers is unconvincing because of the difficulties,
      using conventional epidemiological tools, in ascertaining the quantitative
      contribution made by pulses to cancer risk. Advances in understanding of the
      biological basis of cancer and of the mechanisms of action of cancer-preventing
      compounds offer new insights into the role of food-derived substances and of diet
      gene interactions in modulating cancer risk. Pulses contain a rich variety of
      compounds which, if consumed in sufficient quantities, may help to reduce tumour
      risk.

PMID- 12498628
TI  - Bioavailability of minerals in legumes.
AB  - The mineral content of legumes is generally high, but the bioavailability is poor
      due to the presence of phytate, which is a main inhibitor of Fe and Zn
      absorption. Some legumes also contain considerable amounts of Fe-binding
      polyphenols inhibiting Fe absorption. Furthermore, soya protein per se has an
      inhibiting effect on Fe absorption. Efficient removal of phytate, and probably
      also polyphenols, can be obtained by enzymatic degradation during food
      processing, either by increasing the activity of the naturally occurring plant
      phytases and polyphenol degrading enzymes, or by addition of enzyme preparations.
      Biological food processing techniques that increase the activity of the native
      enzymes are soaking, germination, hydrothermal treatment and fermentation. Food
      processing can be optimized towards highest phytate degradation provided that the
      optimal conditions for phytase activity in the plant is known. In contrast to
      cereals, some legumes have highest phytate degradation at neutral or alkaline pH.
      Addition of microbial enzyme preparations seems to be the most efficient for
      complete degradation during processing. Fe and Zn absorption have been shown to
      be low from legume-based diets. It has also been demonstrated that nutritional Fe
      deficiency reaches its greatest prevalence in populations subsisting on cereal-
      and legume-based diets. However, in a balanced diet containing animal protein a
      high intake of legumes is not considered a risk in terms of mineral supply.
      Furthermore, once phytate, and in certain legumes polyphenols, is degraded,
      legumes would become good sources of Fe and Zn as the content of these minerals
      is high.

PMID- 12498629
TI  - New legume sources as therapeutic agents.
AB  - This review evaluates the potential health benefits of three legume sources that
      rarely appear in Western diets and are often overlooked as functional foods.
      Fenugreek (Trigonella foenum graecum) and isolated fenugreek fractions have been
      shown to act as hypoglycaemic and hypocholesterolaemic agents in both animal and
      human studies. The unique dietary fibre composition and high saponin content in
      fenugreek appears to be responsible for these therapeutic properties. Faba beans
      (Vicia faba) have lipid-lowering effects and may also be a good source of
      antioxidants and chemopreventive factors. Mung beans (Phaseolus aureus, Vigna
      radiatus) are thought to be beneficial as an antidiabetic, low glycaemic index
      food, rich in antioxidants. Evidence suggests that these three novel sources of
      legumes may provide health benefits when included in the daily diet.

PMID- 12498630
TI  - Carbohydrate fractions of legumes: uses in human nutrition and potential for
      health.
AB  - Starch and fibre can be extracted, using wet or dry processes, from a variety of
      grain legumes and used as ingredients for food. alpha-Galactosides can be
      isolated during wet processes from the soluble extract. Starch isolates or
      concentrates are mostly produced from peas, whereas dietary fibre fractions from
      peas and soyabean are commercially available. The physico-chemical
      characteristics of fibre fractions very much depend on their origin, outer fibres
      being very cellulosic whereas inner fibres contain a majority of pectic
      substances. Inner fibres are often used as texturing agents whereas outer fibres
      find their main uses in bakery and extruded products, where they can be
      introduced to increase the fibre content of the food. Most investigations on
      impacts on health have been performed on soyabean fibres. When positive
      observations were made on lipaemia, glucose tolerance or faecal excretion, they
      were unfortunately often obtained after non-realistic daily doses of fibres.
      Legume starches contain a higher amount of amylose than most cereal or tuber
      starches. This confers these starches a lower bioavailability than that of most
      starches, when raw or retrograded. Their low glycaemic index can be considered as
      beneficial for health and especially for the prevention of diseases related to
      insulin resistance. When partly retrograded, these starches can provide
      significant amount of butyrate to the colonic epithelium and may help in colon
      cancer prevention. alpha-Galactosides are usually considered as responsible for
      flatus but their apparent prebiotic effects may be an opportunity to valorize
      these oligosaccharides.

PMID- 12498631
TI  - Non-nutrient bioactive substances of pulses.
AB  - Pulses supply many bioactive substances found in minor amounts in food, but which
      may have significant metabolic and/or physiological effects. These compounds have
      long been classified as antinutritional factors, but many studies have
      reconsidered their impact on health. Some could play a role in the prevention of
      the major diseases of affluent societies. As these compounds can be beneficial or
      adverse, depending on conditions, an assessment of their various physiological
      effects is necessary to determine whether they should be preserved or eliminated
      in each main nutritional situation.

PMID- 12498632
TI  - Larval trematode infections in freshwater snails from the highveld and lowveld
      areas of Zimbabwe.
AB  - Between November 1998 and October 2000, freshwater snails were collected monthly
      from the highveld and lowveld areas of Zimbabwe to determine the occurrence of
      larval trematodes. A total of 13,789 snails, representing ten species, were
      collected from 21 sites and 916 (6.6%) harboured patent trematode infections.
      Eight morphologically distinguishable types of cercariae were identified. Bulinus
      tropicus had the highest overall prevalence of infection (13.1%). The echinostome
      was the most common type of cercaria recovered, contributing 38.2% of all
      infections. Schistosoma cercariae were recovered mainly from the highveld and
      comprised 8.0% of all infections. Amphistome cercariae contributed 37.6% of all
      infections and were recorded from both the highveld and lowveld areas with a peak
      prevalence occurring during the post-rainy period (March-May). The main
      intermediate host for amphistomes was B. tropicus. Infections in B. globosus, B.
      forskalii and Biomphalaria pfeifferi with amphistome cercariae are new records
      for Zimbabwe.

PMID- 12498633
TI  - Predacious activity of Duddingtonia flagrans within the cattle faecal pat.
AB  - Two studies were conducted to investigate the growth and activity of the fungus,
      Duddingtonia flagrans, within cattle faecal pats. Artificial faecal pats were
      constructed with the centre separated from the outer layer by a nylon mesh. Eight
      treatments were tested, by varying the presence/absence of Cooperia oncophora
      eggs and fungal spores within each layer. With parasite eggs in the centre layer,
      a statistically lower recovery of larvae was observed compared to both pats with
      parasite eggs in the periphery and pats with parasite eggs throughout both
      layers. Regardless of location within the pat, if co-located with the parasite
      egg, D. flagrans was found to be effective in trapping developing larvae. The
      reduction in recovery of larvae from pats with parasite eggs and fungal spores in
      the centre was found to be significantly higher than when parasite eggs were in
      the centre and fungal spores in the periphery. In the second study, pats were
      made up in two treatments: pats containing fungal spores and C. oncophora eggs
      (fungus) and pats containing C. oncophora eggs (control). The pats were incubated
      at low or high humidity. Ten pats were used in a cross over where five pats
      incubated at low humidity for 7 weeks were removed, water added and then
      incubated at a high humidity for 1 week. Another five pats were incubated at a
      high humidity for 7 weeks, aerated and incubated at a low humidity for 1 week.
      There was no apparent growth of fungus in faecal pats incubated at a high
      humidity and less than 20% of larvae were recovered. The growth of D. flagrans
      was observed in faecal pats incubated at a low humidity, but a corresponding
      reduction in the percentage recovery of larvae did not occur, except in week 4.
      No statistical difference between fungal and control pats was seen in the change
      over pats. Nematophagous activity was assessed throughout the study and observed
      in the first 4 weeks within the pats containing fungus.

PMID- 12498634
TI  - The effect of cobalt compounds on uninfected and Ascaridia galli-infected
      chickens: a kinetic model for Ascaridia galli populations and chicken growth.
AB  - The effect of dietary cobalt from three different sources on uninfected and
      Ascaridia galli-infected Hisex chickens, has been studied. The chicken diet was
      supplemented with 0.06 Co2+ kg-1 food either in the form of two glycine-cobalt
      compounds or mixed zinc-cobalt basic salt. An excess of dietary cobalt in small
      doses increases the gain of body weight and decreases host mortality. A greater
      bioefficiency of cobalt was established in infected chickens. A mathematical
      model has been used to provide a quantitative interpretation of the observed
      results. The model solutions of the kinetics of worm numbers and body weight are
      in a good agreement with experimental data. The model is valid for different
      degrees of A. galli infections and for treatment with different trace elements.
      The value of the kinetic parameter, regarded as a phenomenological constant of
      the host immune response, depends on the degree of infection.

PMID- 12498635
TI  - Dogs as alternative intermediate hosts of Taenia solium in Papua (Irian Jaya),
      Indonesia confirmed by highly specific ELISA and immunoblot using native and
      recombinant antigens and mitochondrial DNA analysis.
AB  - Serology (ELISA and immunoblot) using native glycoproteins, affinity purified
      glycoproteins, and a recombinant antigen is known to be highly specific to Taenia
      solium cysticercosis in humans and pigs. These techniques were applied for dogs
      in the highly endemic area of cysticercosis in Papua (Irian Jaya), Indonesia.
      Analysis of dog sera by both ELISA and immunoblot revealed 7 of 64 dogs were
      highly positive. Examination of two sero-positive dogs revealed cysticerci of T.
      solium in the brain and heart of these dogs. Mitochondrial DNA analysis confirmed
      that they were the same as T. solium previously confirmed from pigs and biopsies
      from local people from Irian Jaya. It is suggested that the life cycle of T.
      solium may be completed not only between humans and pigs but also between humans
      and dogs.

PMID- 12498636
TI  - Long-term stability in the richness and structure of helminth communities in
      eels, Anguilla anguilla, in Lough Derg, River Shannon, Ireland.
AB  - A data set on intestinal helminth parasites was collected in the course of an 18
      year investigation into the biology of eels in Meelick Bay, Lough Derg, River
      Shannon. This was used to test two hypotheses relating to the composition and
      structure of intestinal helminth communities, namely that eels in large rivers do
      not harbour richer and more diverse communities than those in small rivers but
      that community composition and structure are more stable over time than in small
      rivers. The helminth community was species poor, with only six species comprising
      the component community and a maximum infracommunity richness of three species.
      The community was overwhelmingly dominated by the acanthocephalan Acanthocephalus
      lucii, reflecting the importance of its intermediate host Asellus aquaticus in
      the eels' diet. The remaining helminth species contributed to species richness
      but made very little contribution to community diversity. Population levels of
      Acanthocephalus lucii fell and remained low between 1992 and 2000, probably
      reflecting increased movement of eels from other parts of the lough into Meelick
      Bay. Diversity values were low, but similar to those reported from other rivers
      in Britain and Europe. The results provided support for both hypotheses and
      indicated that in respect of richness, diversity and dominance, the helminth
      communities of eels in the River Shannon were typical of, and comparable to,
      those of other large rivers throughout Europe.

PMID- 12498637
TI  - Effect of acanthocephalan parasites on hiding behaviour in two species of shore
      crabs.
AB  - The effect of acanthocephalan parasites (Profilicollis spp.) on the hiding
      behaviour during low tide of two species of shore crabs (intermediate hosts),
      Macrophthalmus hirtipes (Brachyura: Ocypodidae) and Hemigrapsus crenulatus
      (Brachyura: Grapsidae), was examined at Blueskin Bay, South Island, New Zealand.
      Exposed M. hirtipes were found to have significantly higher infection levels than
      did hidden conspecifics. This pattern was not observed for H. crenulatus. Mean
      cystacanth numbers were found to be considerably higher in M. hirtipes than H.
      crenulatus. Crabs exposed at low tide are at a greater risk of predation by
      definitive shorebird hosts than are hidden conspecifics. Preferential
      manipulation of one intermediate host species over another could influence
      diversity within ecosystems.

PMID- 12498638
TI  - Adult worm tegumental damage and egg-granulomas in praziquantel-resistant and 
      susceptible Schistosoma mansoni treated in vivo.
AB  - The effect of treatment with praziquantel (PZQ) on the tegument of adult
      Schistosoma mansoni worms and on liver egg-granulomas has been examined in mice
      infected with PZQ-resistant and -susceptible parasite isolates. Two PZQ-resistant
      S. mansoni isolates, one selected by passage in the laboratory under drug
      pressure and one from Senegal established from eggs excreted by an uncured
      patient, were compared with PZQ-susceptible control isolates. Scanning electron
      microscopic observations on the tegument of Schistosoma adult worms treated in
      vivo with PZQ showed that more severe damage was inflicted by PZQ on susceptible
      worms than on drug-resistant worms. Observations on the pathology of Schistosoma
      egg-granulomas in the liver of infected mice after treatment with PZQ indicated
      that eggs from susceptible control isolates were more sensitive to PZQ than those
      from drug-resistant isolates.

PMID- 12498639
TI  - Immunodiagnosis of ocular toxocariasis using Western-blot for the detection of
      specific anti-Toxocara IgG and CAP for the measurement of specific anti-Toxocara
      IgE.
AB  - A prospective multicentric study was carried out to assess both the performance
      of Western-blot (WB) detecting specific anti-Toxocara IgG and that of CAP
      measuring specific IgE titre for the immunodiagnosis of ocular toxocariasis. For
      14 outpatients presenting ophthalmic symptoms (choroiditis, chorioretinitis,
      papillar oedema, hyalitis, retinal detachment and/or uveitis), samples of serum
      and aqueous fluid (AF) were sent to the Department of Parasitology, University
      Hospitals, Toulouse, France. All patients but two tested positive with WB on the
      serum; 13 WB tests were performed on the AF, 12 of which were positive. The two
      patients who had a negative WB serum result tested positive for the AF. Specific
      IgE detection was considered as a complementary test of WB. Two patients showed a
      greater specific IgE titre in the AF than in the serum, and one had a positive
      result in the AF, but not in the serum. These six patients were considered as
      clear cases of ocular toxocariasis. Western-blot coupled with specific anti
      Toxocara IgE detection appeared therefore to be an accurate procedure for the
      immunodiagnosis of ocular toxocariasis, provided the testing was simultaneously
      performed on the serum and AF.

PMID- 12498640
TI  - The Hydrobia ulvae-Maritrema subdolum association: influence of temperature,
      salinity, light, water-pressure and secondary host exudates on cercarial
      emergence and longevity.
AB  - The effects of environmental factors and exudates from the amphipod Corophium
      volutator on the emergence of Maritrema subdolum cercariae (Digenea:
      Microphallidae) from the snail Hydrobia ulvae were investigated in the
      laboratory. Increasing the temperature (15 to 25 degrees C) caused an overall 11
      fold increase in emergence rate under varying salinities (24 to 36 per thousand).
      The effect of salinity depended on the experimental temperature. Emergence
      increased with increasing salinity at higher temperatures, but decreased with
      increasing salinity at 15 degrees C. Whereas the different levels of salinity had
      no effect, increasing the temperature significantly reduced the life span of
      cercariae. In comparison with complete darkness, light caused a two-fold increase
      in emergence, whereas an increment of the water pressure from 1.0 to 1.3 ATM
      (corresponding to 0 and 3 m of depth) left the shedding rate unaffected.
      Unidentified exudates from the second intermediate host, C. volutator,
      significantly depressed the cercarial emergence rate. The main transmission
      window of M. subdolum seems to occur during low water in tidal pools where light
      levels are high and solar radiation rapidly elevates the water temperature, as
      well as salinity through evaporation. The consequence of such a transmission
      strategy is discussed in relation to the impact of M. subdolum on the population
      dynamics of the second intermediate host.

PMID- 12498641
TI  - The Hydrobia ulvae-Maritrema subdolum association: cercarial emergence controlled
      by host activity.
AB  - The release of Maritrema subdolum cercariae (Digenea: Microphallidae) from the
      marine mud snail Hydrobia ulvae is significantly affected by temperature,
      salinity, light and exudates from the second intermediate amphipod host. Based on
      (i) previously published data on temperature-salinity dependent H. ulvae
      activity, (ii) new experimental data on H. ulvae activity in light and darkness
      as well as in the presence and absence of host exudates, and (iii) the cercarial
      emergence rate from free moving snails and snails prevented from crawling, the
      present analysis indicates that emergence of M. subdolum larvae is regulated
      mainly by host activity as the ultimate factor for release. The adaptive
      significance of such an emergence strategy is emphasized.

PMID- 12498642
TI  - Helminth communities of two sympatric skinks (Mabuya agilis and Mabuya
      macrorhyncha) from two "restinga" habitats in southeastern Brazil.
AB  - The helminth fauna of two sympatric congeneric skinks (Mabuya agilis and M.
      macrorhyncha) from two distinct "restinga" habitats (Praia das Neves and Grussai)
      in southeastern Brazil were studied, totalling four data sets (sample sizes
      ranging from 11 to 28). A total of ten helminth species were associated with the
      skinks: Raillietiella sp., Paradistomum parvissimum, Pulchrosomoides elegans,
      Oochoristica ameivae, Hexametra boddaertii, Parapharyngodon sceleratus,
      Physalopteroides venancioi, Physaloptera sp., an unidentified acuariid nematode
      and an unidentified centrorhynchid acanthocephalan. Except for Hexametra
      boddaertii (found only in Grussai) and Pulchrosomoides elegans (found only in
      Praia das Neves), all helminth species were present at both localities. Half of
      the helminth species were present only as larvae and, in most cases, appear to
      represent paratenic parasitism. Overall prevalences of infection were high for
      both host species in both localities. Mabuya agilis tended to have richer and
      more diverse infracommunities than M. macrorhyncha. Some parameters of infection
      by individual helminth species seem to be related to the ecology of each Mabuya
      species. The parasite faunas were qualitatively very similar among species and/or
      localities, but quantitative similarities were more varied, due to differential
      representativeness of individual helminth species among host populations. The
      helminth communities of both skink species can be classified as non-interactive,
      being composed of site-specialists and immature stages of non-lizard parasites.

PMID- 12498643
TI  - The response of Anisakis larvae to freezing.
AB  - Anisakis third stage larvae utilize a variety of fish as intermediate hosts.
      Uncooked fish are rendered safe for human consumption by freezing. Larvae freeze
      by inoculative freezing from the surrounding medium but can survive freezing at
      temperatures down to -10 degrees C. This ability may be aided by the production
      of trehalose, which can act as a cryoprotectant, but does not involve
      recrystallization inhibition. Monitoring of fish freezing in commercial blast
      freezers and under conditions which simulate those of a domestic freezer,
      indicate that it can take a long time for all parts of the fish to reach a
      temperature that will kill the larvae. This, and the moderate freezing tolerance
      of larvae, emphasizes the need for fish to be frozen at a low enough temperature
      and for a sufficient time to ensure that fish are safe for consumption.

PMID- 12498644
TI  - Emergence of cercariae of Echinostoma caproni and Schistosoma mansoni from
      Biomphalaria glabrata under different laboratory conditions.
AB  - Release of Echinostoma caproni cercariae and Schistosoma mansoni from
      experimentally infected Biomphalaria glabrata snails maintained under different
      laboratory conditions was studied. Infected snails were isolated individually for
      1 h in Stender dishes containing 5 ml of artificial spring water and the number
      of cercariae released during this time was recorded. Of numerous conditions
      tested, the addition of lettuce, the use of water conditioned by B. glabrata
      snails and a temperature of 35 degrees C significantly increased the release of
      E. caproni cercariae. A significant increase in cercarial release of S. mansoni
      was seen only in cultures fed lettuce. A temperature of 12 degrees C caused a
      significant decrease in cercarial release of both E. caproni and S. mansoni.
      Increased snail activity associated with feeding behaviour was probably
      responsible for the enhanced cercarial sheds observed in this study.

PMID- 12498645
TI  - Qualitative and quantitative aspects of recent research on helminth parasites.
AB  - Relationships between the species diversity of different taxa, the mean number of
      articles published per year on each taxon, and the mean impact factor of the
      journals in which they appear, were examined across six taxa of helminths:
      Nematomorpha, Acanthocephala, Monogenea, Trematoda, Cestoda and Nematoda, the
      latter including only animal parasitic nematodes. The mean annual output of
      scientific articles per taxon was not related to the species diversity of these
      taxa or, at least, not significantly. Thus, the large volume of publications on
      nematodes is not merely a reflection of their estimated diversity. There were
      significant differences among taxa in the mean impact factor of the journals in
      which papers on each taxon appeared, with nematodes having the highest mean
      score, followed by trematodes and cestodes. In addition, across the six taxa, the
      mean journal impact factor correlated positively and significantly with the mean
      annual number of papers published: not only are there more papers published on
      nematodes and trematodes than on nematomorphs or acanthocephalans, but they are
      also generally published in higher-ranking journals. These results suggest that
      there is an increasing gap in the quantity and general importance of the research
      carried out on different helminth taxa.

PMID- 12498649
TI  - First Isolation of West Nile virus from a patient with encephalitis in the United
      States.
AB  - West Nile virus (WNV) was isolated from a patient who developed encephalitis
      while undergoing treatment with CHOP (cyclophosphamide, hydroxydoxorubicin,
      vincristine [Oncovin], predisone) and rituximab for a non-Hodgkin B-cell
      lymphoma. Both standard reverse transcription-polymerase chain reaction (RT-PCR)
      and Taqman RT-PCR established the diagnosis of WNV infection from cerebrospinal
      fluid (CSF). Several whole blood samples and one serum sample underwent further
      testing. CSF and serum samples were negative for WNV antibody; however, all
      samples were positive by both RT-PCR assays. Infectious virus was recovered from
      a blood sample, and its identity was confirmed by using a WNV-specific
      immunofluorescence assay. The complete WNV genomes determined from CSF and from
      the virus isolate adapted from cell culture were the same. The results represent
      the first complete WNV genome sequence obtained directly from human CSF and the
      first time that infectious WNV has been recovered from a patient with
      encephalitis in North America.

PMID- 12498650
TI  - West Nile virus epidemic in horses, Tuscany region, Italy.
AB  - During the late summer of 1998, veterinary authorities in Tuscany, Italy,
      received reports of cases of neurologic disease among horses residing in a large
      wetland area located in the provinces of Florence and Pistoia. West Nile virus
      was isolated from two of the six horses that died or were euthanized. A
      retrospective epidemiologic study identified 14 clinical neurologic cases that
      occurred from August 20 to October 6 (attack rate of 2.8%). A serologic survey
      conducted over a 700-km2 area in stables with and without apparent clinical cases
      confirmed a wider spread of the infection, with an overall seroprevalence rate of
      38% in the affected area. No significant differences in age-specific prevalence
      were observed, suggesting that the horses residing in the area had not been
      exposed previously to West Nile virus and supporting the hypothesis of its
      introduction in the wetland area during the first half of 1998.

PMID- 12498651
TI  - Induction of inflammation by West Nile virus capsid through the caspase-9
      apoptotic pathway.
AB  - West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne
      pathogens. Clinical signs of WNV infection include neurologic symptoms, limb
      weakness, and encephalitis, which can result in paralysis or death. We report
      that the WNV-capsid by itself induces rapid nuclear condensation and cell death
      in tissue culture. Apoptosis is induced through the mitochondrial pathway
      resulting in caspase-9 activation and downstream caspase-3 activation. Capsid
      gene delivery into the striatum of mouse brain or interskeletal muscle resulted
      in cell death and inflammation, likely through capsid-induced apoptosis in vivo.
      These studies demonstrate that the capsid protein of WNV may be responsible for
      aspects of viral pathogenesis through induction of the apoptotic cascade.

PMID- 12498652
TI  - Vector competence of California mosquitoes for West Nile virus.
AB  - To identify the mosquito species competent for West Nile virus (WNV)
      transmission, we evaluated 10 California species that are known vectors of other
      arboviruses or major pests: Culex tarsalis, Cx. pipiens pipiens, Cx. p.
      quinquefasciatus, Cx. stigmatosoma, Cx. erythrothorax, Ochlerotatus dorsalis, Oc.
      melanimon, Oc. sierrensis, Aedes vexans, and Culiseta inornata. All 10 became
      infected and were able to transmit WNV at some level. Ochlerotatus, Culiseta, and
      Aedes were low to moderately efficient vectors. They feed primarily on mammals
      and could play a secondary role in transmission. Oc. sierrensis, a major pest
      species, and Cx. p. quinquefasciatus from southern California were the least
      efficient laboratory vectors. Cx. tarsalis, Cx. stigmatosoma, Cx. erythrothorax,
      and other populations of Cx. pipiens complex were the most efficient laboratory
      vectors. Culex species are likely to play the primary role in the enzootic
      maintenance and transmission of WNV in California.

PMID- 12498653
TI  - Efficacy of killed virus vaccine, live attenuated chimeric virus vaccine, and
      passive immunization for prevention of West Nile virus encephalitis in hamster
      model.
AB  - Results of experiments evaluating the efficacy of three immunization strategies
      for the prevention of West Nile virus (WNV) encephalitis are reported.
      Immunization strategies evaluated included a killed virus veterinary vaccine, a
      live attenuated chimeric virus vaccine candidate, and passive immunization with
      WNV-immune serum; all were tested by using a hamster model of the disease. Each
      product protected the animals from clinical illness and death when challenged
      with a hamster-virulent ewild-type WNV strain 1 month after initial immunization.
      The live attenuated chimeric virus vaccine candidate induced the highest humoral
      antibody responses, as measured by hemagglutination inhibition, complement
      fixation, and plaque reduction neutralization tests. Although the duration of
      protective immunity was not determined in this study, our preliminary results and
      the cumulative experience of other virus vaccines suggest that the live
      attenuated chimeric virus provides the longest lasting immunity.

PMID- 12498654
TI  - Mass vaccination campaign following community outbreak of meningococcal disease.
AB  - During December 12-29, 1998, seven patients ages 2-18 years were diagnosed with
      serogroup C meningococcal disease in two neighboring Florida towns with 33,000
      residents. We evaluated a mass vaccination campaign implemented to control the
      outbreak. We maintained vaccination logs and recorded the resources used in the
      campaign that targeted 2- to 22-year-old residents of the two towns. A total of
      13,148 persons received the vaccinations in 3 days. Vaccination coverage in the
      target population was estimated to be 86% to 99%. Five additional cases of
      serogroup C meningococcal disease occurred in the community during the year after
      the campaign began, four in patients who had not received the vaccine. The cost
      of control efforts was approximately $370,000. Although cases continued to occur,
      the vaccination campaign appeared to control the outbreak. Rapid implementation,
      a targeted approach, and high coverage were important to the campaign's success.

PMID- 12498655
TI  - Meteorologic influences on Plasmodium falciparum malaria in the Highland Tea
      Estates of Kericho, Western Kenya.
AB  - Recent epidemics of Plasmodium falciparum malaria have been observed in high
      altitude areas of East Africa. Increased malaria incidence in these areas of
      unstable malaria transmission has been attributed to a variety of changes
      including global warming. To determine whether the reemergence of malaria in
      western Kenya could be attributed to changes in meteorologic conditions, we
      tested for trends in a continuous 30-year monthly malaria incidence dataset (1966
      1995) obtained from complete hospital registers at a Kenyan tea plantation.
      Contemporary monthly meteorologic data (1966-1995) that originated from the tea
      estate meteorologic station and from global climatology records were also tested
      for trends. We found that total hospital admissions (malaria and nonmalaria)
      remained unchanged while malaria admissions increased significantly during the
      period. We also found that all meteorologic variables showed no trends for
      significance, even when combined into a monthly suitability index for malaria
      transmission. We conclude that climate changes have not caused the highland
      malaria resurgence in western Kenya.

PMID- 12498656
TI  - Antimicrobial resistance of Escherichia coli O26, O103, O111, O128, and O145 from
      animals and humans.
AB  - Susceptibilities to fourteen antimicrobial agents important in clinical medicine
      and agriculture were determined for 752 Escherichia coli isolates of serotypes
      O26, O103, O111, O128, and O145. Strains of these serotypes may cause urinary
      tract and enteric infections in humans and have been implicated in infections
      with Shiga toxin-producing E. coli (STEC). Approximately 50% of the 137 isolates
      from humans were resistant to ampicillin, sulfamethoxazole, cephalothin,
      tetracycline, or streptomycin, and approximately 25% were resistant to
      chloramphenicol, trimethoprim-sulfamethoxazole, or amoxicillin-clavulanic acid.
      Approximately 50% of the 534 isolates from food animals were resistant to
      sulfamethoxazole, tetracycline, or streptomycin. Of 195 isolates with STEC
      related virulence genes, approximately 40% were resistant to sulfamethoxazole,
      tetracycline, or streptomycin. Findings from this study suggest antimicrobial
      resistance is widespread among E. coli O26, O103, O111, O128, and O145 inhabiting
      humans and food animals.

PMID- 12498657
TI  - Genetic analysis of viruses associated with emergence of Rift Valley fever in
      Saudi Arabia and Yemen, 2000-01.
AB  - The first confirmed Rift Valley fever outbreak outside Africa was reported in
      September 2000, in the Arabian Peninsula. As of February 2001, a total of 884
      hospitalized patients were identified in Saudi Arabia, with 124 deaths. In Yemen,
      1,087 cases were estimated to have occurred, with 121 deaths. Laboratory
      diagnosis of Rift Valley fever virus (RVFV) infections included virus genetic
      detection and characterization of clinical specimens by reverse transcription
      polymerase chain reaction, in addition to serologic tests and virus isolation.
      Genetic analysis of selected regions of virus S, M, and L RNA genome segments
      indicated little genetic variation among the viruses associated with disease. The
      Saudi Arabia and Yemen viruses were almost identical to those associated with
      earlier RVF epidemics in East Africa. Analysis of S, M, and L RNA genome segment
      sequence differences showed similar phylogenetic relationships among these
      viruses, indicating that genetic reassortment did not play an important role in
      the emergence of this virus in the Arabian Peninsula. These results are
      consistent with the recent introduction of RVFV into the Arabian Peninsula from
      East Africa.

PMID- 12498658
TI  - Co-feeding transmission and its contribution to the perpetuation of the lyme
      disease spirochete Borrelia afzelii.
AB  - To determine whether direct passage of spirochetes between co-feeding vector
      ticks contributes to the likelihood that the Lyme disease spirochete Borrelia
      afzelii will perpetuate in nature, we compared the effects of time and space on
      transmission efficiency between simultaneously feeding ticks. The likelihood of
      co-feeding transmission increases with duration of attachment of the infecting
      tick. Co-feeding transmission becomes less efficient as distance from the
      infecting tick increases. Approximately 6 times as many ticks acquire infection
      when feeding on infected mice than when co-feeding with infected ticks. Both
      subadult stages of the wood tick Ixodes ricinus infrequently co-infest mice and
      voles in nature; on approximately 1 in 20 small rodents, larvae co-feed with
      spirochete-infected nymphs. Because only 1 in 100 larvae in nature appear to
      acquire spirochetal infection when co-feeding with infected nymphs, perpetuation
      of B. afzelii depends largely on horizontal transmission of such pathogens from
      previously infected mice to noninfected larvae.

PMID- 12498659
TI  - Binary cumulative sums and moving averages in nosocomial infection cluster
      detection.
AB  - Clusters of nosocomial infection often occur undetected, at substantial cost to
      the medical system and individual patients. We evaluated binary cumulative sum
      (CUSUM) and moving average (MA) control charts for automated detection of
      nosocomial clusters. We selected two outbreaks with genotyped strains and used
      resistance as inputs to the control charts. We identified design parameters for
      the CUSUM and MA (window size, k, alpha, Beta, p(0), p(1)) that detected both
      outbreaks, then calculated an associated positive predictive value (PPV) and time
      until detection (TUD) for sensitive charts. For CUSUM, optimal performance (high
      PPV, low TUD, fully sensitive) was for 0.1 < or = alpha < or = 0.25 and 0.2 < or
      = Beta < or = 0.25, with p(0) = 0.05, with a mean TUD of 20 (range 8-43)
      isolates. Mean PPV was 96.5% (relaxed criteria) to 82.6% (strict criteria). MAs
      had a mean PPV of 88.5% (relaxed criteria) to 46.1% (strict criteria). CUSUM and
      MA may be useful techniques for automated surveillance of resistant infections.

PMID- 12498660
TI  - Using automated health plan data to assess infection risk from coronary artery
      bypass surgery.
AB  - We determined if infection indicators were sufficiently consistent across health
      plans to allow comparison of hospitals' risks of infection after coronary artery
      bypass surgery. Three managed care organizations accounted for 90% of managed
      care in eastern Massachusetts, from October 1996 through March 1999. We searched
      their automated inpatient and outpatient claims and outpatient pharmacy
      dispensing files for indicator codes suggestive of postoperative surgical site
      infection. We reviewed full text medical records of patients with indicator codes
      to confirm infection status. We compared the hospital-specific proportions of
      cases with an indicator code, adjusting for health plan, age, sex, and chronic
      disease score. A total of 536 (27%) of 1,953 patients had infection indicators.
      Infection was confirmed in 79 (53%) of 149 reviewed records with adequate
      documentation. The proportion of patients with an indicator of infection varied
      significantly (p < 0.001) between hospitals (19% to 36%) and health plans (22% to
      33%). The difference between hospitals persisted after adjustment for health plan
      and patients' age and sex. Similar relationships were observed when postoperative
      antibiotic information was ignored. Automated claims and pharmacy data from
      different health plans can be used together to allow inexpensive, routine
      monitoring of indicators of postoperative infection, with the goal of identifying
      institutions that can be further evaluated to determine if risks for infection
      can be reduced.

PMID- 12498661
TI  - Cross-sectional study on influenza vaccination, Germany, 1999-2000.
AB  - To assess influenza vaccination coverage in Germany, we conducted a nationwide
      telephone survey in November 1999 in adults (>18 yrs) using random-digit dialing.
      Overall, 23% of 1,190 survey participants reported having been vaccinated
      (adjusted 18%) with 16% (adjusted 15%) in former West Germany versus 35%
      (adjusted 32%) in former East Germany. Immunization rates for vaccination target
      groups were lower in West Germany (21%) than in East Germany (40%). Seven percent
      of health-care workers were immunized. Previous influenza vaccination, positive
      attitudes towards immunization, and having a family physician increased the rate
      of vaccination; fear of adverse effects lowered the rate. Family physicians
      performed 93% of the vaccinations, which suggests their key role in improving low
      vaccination coverage in Germany. The fact that >71% (850/1,190) of participants
      belonged to at least one of the vaccination target groups recommended by the
      German Standing Commission on Immunization emphasizes the need to focus the
      definition of target groups.

PMID- 12498662
TI  - Legionnaires' disease at a Dutch flower show: prognostic factors and impact of
      therapy.
AB  - After a large outbreak of Legionnaires' disease in the Netherlands, we determined
      risk factors for intensive care unit (ICU) admission and death and the impact of
      adequate therapy on ICU-free survival among 141 hospitalized patients. Overall
      mortality rate was 13%, and ICU mortality rate was 36%. Smoking, temperature
      >38.5 degrees C, and bilateral infiltrates shown on chest x-ray were independent
      risk factors for ICU admission or death (all p<0.05). Starting adequate therapy
      within 24 hours after admission resulted in a higher ICU-free survival rate
      compared to therapy initiation after 24 hours: 78% versus 54%, respectively
      (p=0.005). However, delay in providing therapy to patients with urinary antigen
      tests with negative results did not influence outcome. These data suggest that by
      using the urinary antigen test on admission a more tailored approach to patients
      with community-acquired pneumonia may be applied.

PMID- 12498663
TI  - Leptospirosis: skin wounds and control strategies, Thailand, 1999.
AB  - After an outbreak of leptospirosis in workers who participated in cleaning a pond
      during September 1999 in Thailand, a serologic survey was conducted. Among a
      cohort of 104 persons from one village who participated in pond cleaning
      activity, 43 (41.3%) were seropositive for immunoglobulin M antibodies against
      Leptospira, indicating recent infection. Only 17 (39.5%) of 43 seropositive
      persons reported a recent febrile illness; the remaining seropositive persons
      were considered asymptomatic, suggesting that asymptomatic leptospirosis
      infection may be common where leptospirosis is endemic. Multivariable logistic
      regression indicated that wearing long pants or skirts was independently
      protective against leptospirosis infection (OR(adjusted) = 0.217), while the
      presence of more than two wounds on the body was independently associated with
      infection (OR(adjusted) = 3.97). Educational efforts should be enhanced in areas
      where leptospirosis is endemic to encourage the use of protective clothing. In
      addition, wound management and avoidance of potentially contaminated water when
      skin wounds are present should be included in health education programs.

PMID- 12498664
TI  - Outpatient antibiotic use and prevalence of antibiotic-resistant pneumococci in
      France and Germany: a sociocultural perspective.
AB  - The prevalence of penicillin-nonsusceptible pneumococci is sharply divided
      between France (43%) and Germany (7%). These differences may be explained on
      different levels: antibiotic-prescribing practices for respiratory tract
      infections; patient-demand factors and health-belief differences; social
      determinants, including differing child-care practices; and differences in
      regulatory practices. Understanding these determinants is crucial for the success
      of possible interventions. Finally, we emphasize the overarching importance of a
      sociocultural approach to preventing antibiotic resistance in the community.

PMID- 12498665
TI  - Identifying reservoirs of infection: a conceptual and practical challenge.
AB  - Many infectious agents, especially those that cause emerging diseases, infect
      more than one host species. Managing reservoirs of multihost pathogens often
      plays a crucial role in effective disease control. However, reservoirs remain
      variously and loosely defined. We propose that reservoirs can only be understood
      with reference to defined target populations. Therefore, we define a reservoir as
      one or more epidemiologically connected populations or environments in which the
      pathogen can be permanently maintained and from which infection is transmitted to
      the defined target population. Existence of a reservoir is confirmed when
      infection within the target population cannot be sustained after all transmission
      between target and nontarget populations has been eliminated. When disease can be
      controlled solely by interventions within target populations, little knowledge of
      potentially complex reservoir infection dynamics is necessary for effective
      control. We discuss the practical value of different approaches that may be used
      to identify reservoirs in the field.

PMID- 12498666
TI  - Dengue hemorrhagic fever in infants: research opportunities ignored.
AB  - The age distribution of cases of dengue hemorrhagic fever and dengue shock
      syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok,
      Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar;
      and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants,
      all of whom were having a primary dengue infection. Progress studying the
      immunologically distinct infant DHF/DSS has been limited; most contemporary
      research has centered on DHF/DSS accompanying secondary dengue infections. In
      designing research results obtained in studies on a congruent animal model,
      feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV
      immune queens should be considered. Research challenges presented by infant
      DHF/DSS are discussed.

PMID- 12498667
TI  - Role of the domestic chicken (Gallus gallus) in the epidemiology of urban
      visceral leishmaniasis in Brazil.
AB  - Zoonotic visceral leishmaniasis (ZVL) is a serious public health problem in
      several Brazilian cities. Although the proximity of chicken houses is often cited
      as a risk factor in studies of urban ZVL, the role chickens play in the
      epidemiology of the disease has not been defined. Chickens attract both male and
      female sand flies (Lutzomyia longipalpis) but are unable to sustain Leishmania
      infections, and their presence may exert a zooprophylactic effect. We discuss
      environmental, physiologic, socioeconomic, and cultural factors related to
      chicken raising that could influence Le. infantum transmission in Brazilian
      cities and evaluate whether this practice significantly affects the risk of
      acquiring ZVL.

PMID- 12498668
TI  - Antimicrobial resistance in Streptococcus pneumoniae, Taiwan.
AB  - Taiwan has one of the highest levels of antibiotic-resistant pneumococcus in the
      world. Pneumococcal isolates not susceptible to penicillin first appeared in
      Taiwan in 1986; in 1995 an increase in the prevalence of nonsusceptibility to
      penicillins, extended-spectrum cephalosporins, trimethoprim-sulfamethoxazole, and
      macrolides as well as multidrug resistance began to be recognized. With the
      persistence of antibiotic selective pressure, resistance in some antibiotics
      reached a high plateau (beta-lactam antibiotics) or continued to increase
      (macrolides), while novel resistance (fluoroquinolones) emerged in the last 3
      years. Widespread distribution of some novel resistant 23F and 19F clones (and
      the international epidemic of 23F clones) contributes further to the rapid
      increase of resistance. Because Streptococcus pneumoniae is a major pathogen that
      causes community-acquired lower respiratory tract infections and meningitis in
      adults and children, antibiotic-resistance in this organism is a serious problem.

PMID- 12498669
TI  - Isolation and genetic characterization of Rift Valley fever virus from Aedes
      vexans arabiensis, Kingdom of Saudi Arabia.
AB  - An outbreak of Rift Valley fever in the Kingdom of Saudi Arabia and Yemen in 2000
      was the first recognized occurrence of the illness outside of Africa and
      Madagascar. An assessment of potential mosquito vectors in the region yielded an
      isolate from Aedes vexans arabiensis, most closely related to strains from
      Madagascar (1991) and Kenya (1997).

PMID- 12498670
TI  - Rat-to-human transmission of Cowpox infection.
AB  - We isolated Cowpox virus (CPXV) from the ulcerative eyelid lesions of a 14-year
      old girl, who had cared for a clinically ill wild rat that later died. CPXV
      isolated from the rat (Rattus norvegicus) showed complete homology with the
      girl's virus. Our case is the first proven rat-to-human transmission of cowpox.

PMID- 12498671
TI  - Naturally occurring Ehrlichia chaffeensis infection in two prosimian primate
      species: ring-tailed lemurs (Lemur catta) and ruffed lemurs (Varecia variegata).
AB  - A naturally occurring infection of Ehrlichia chaffeensis in lemurs is described.
      DNA of Ehrlichia chaffeensis was identified by polymerase chain reaction in
      peripheral blood from six of eight clinically ill lemurs. Organisms were cultured
      from the blood of one lemur exhibiting clinical and hematologic abnormalities
      similar to those of humans infected with E. chaffeensis.

PMID- 12498672
TI  - Increasing fluoroquinolone resistance in Campylobacter jejuni, Pennsylvania,
      USA,1982-2001.
AB  - Fluoroquinolone-resistant Campylobacter jejuni has been observed worldwide and is
      now being seen in the United States. Among patients in our health-care system in
      Pennsylvania, fluoroquinolone-resistant C. jejuni were not observed from 1982 to
      1992; however, resistance increased to 40.5% in 2001. Resistance to erythromycin
      remains at a low level (<5%).

PMID- 12498673
TI  - New variant of varicella-zoster virus.
AB  - In 1998, a varicella-zoster virus glycoprotein E (gE) mutant virus (VZV-MSP) was
      isolated from a child with chickenpox. VZV-MSP, representing a second VZV
      serotype, was considered a rarity. We isolated another VZV-MSP-like virus from an
      elderly man with herpes zoster. These gE mutant viruses may have arisen through
      independent mutation or may represent a distinct VZV subpopulation that emerged
      more than 50 years ago.

PMID- 12498674
TI  - Plasmodium ovale malaria acquired in central Spain.
AB  - We describe a case of locally acquired Plasmodium ovale malaria in Spain. The
      patient was a Spanish woman who had never traveled out of Spain and had no other
      risk factors for malaria. Because patients with malaria may never have visited
      endemic areas, occasional transmission of malaria to European hosts is a
      diagnostic and clinical challenge.

PMID- 12498675
TI  - Puumala hantavirus infection in humans and in the reservoir host, Ardennes
      region, France.
AB  - We compared the occurrence of nephropathia epidemica cases, over a multi-annual
      population cycle, in northeastern France with the hantavirus serology for bank
      voles captured in the same area. We discuss hypotheses to explain the pattern of
      infection in both humans and rodents and their synchrony.

PMID- 12498676
TI  - Capsule switching among C:2b:P1.2,5 meningococcal epidemic strains after mass
      immunization campaign, Spain.
AB  - A mass immunization campaign for 18-month to 19-year-olds was undertaken in Spain
      in 1996-1997 because of an epidemic of serogroup C meningococcal disease
      associated with a C:2b:P1.2,5 strain belonging to the A4 lineage. Surveillance
      for the "capsule-switching" phenomenon producing B:2b:P1.2,5 isolates was
      undertaken. Of 2,975 meningococci characterized, B:2b:P1.2,5 and B:2b:P1.2
      antigenic combinations were found in 18 isolates; 15 meningococci were defined as
      serogroup B belonging to the A4 lineage.

PMID- 12498677
TI  - Human pathogens in body and head lice.
AB  - Using polymerase chain reaction and sequencing, we investigated the prevalence of
      Rickettsia prowazekii, Bartonella quintana, and Borrelia recurrentis in 841 body
      lice collected from various countries. We detected R. prowazekii in body lice
      from Burundi in 1997 and in lice from Burundi and Rwanda in 2001; B. quintana
      infections of body lice were widespread. We did not detect B. recurrentis in any
      lice.

PMID- 12498678
TI  - Clinical failures of linezolid and implications for the clinical microbiology
      laboratory.

PMID- 12498679
TI  - Avian reservoirs of the agent of human granulocytic ehrlichiosis?

PMID- 12498680
TI  - Emerging leptospirosis, North India.

PMID- 12498681
TI  - A Formin Homology protein and a profilin are required for cytokinesis and Arp2/3
      independent assembly of cortical microfilaments in C. elegans.
AB  - BACKGROUND: F-actin is enriched at the cortex of embryonic cells in the nematode
      Caenorhabditis elegans and is required for multiple processes that include the
      establishment of an anterior-posterior (A-P) axis and cytokinesis. However, the
      mechanisms that regulate cortical microfilament (MF) assembly remain poorly
      understood. RESULTS: We show here that a profilin called PFN-1 accumulates at the
      cortex independent of the actin cytoskeleton and is required for the assembly or
      maintenance of cortical MFs and myosin. Reducing PFN-1 levels by RNAi results in
      cytokinesis and A-P polarity defects. PFN-1 binds to the Formin Homology (FH)
      protein CYK-1, which also is required for cortical MFs. In contrast to PFN-1 and
      CYK-1, the Arp2/3 complex appears to be dispensable for the assembly of cortical
      MFs, for A-P polarity, and for cytokinesis. Instead, the Arp2/3 complex is
      required for cell migrations that occur during gastrulation and may also be
      involved in cellular rearrangements required for epidermal enclosure prior to
      elongation of ovoid embryos into vermiform larvae. CONCLUSIONS: We conclude that
      the FH protein CYK-1 and the profilin PFN-1 mediate the Arp2/3-independent
      assembly of MFs and are required for cytokinesis in the early embryo. These data
      suggest that CYK-1 and PFN-1 may nucleate MFs, as has recently been shown for an
      FH protein and a profilin in yeast.

PMID- 12498682
TI  - Live imaging of telomeres: yKu and Sir proteins define redundant telomere
      anchoring pathways in yeast.
AB  - BACKGROUND: The positioning of chromosomal domains within interphase nuclei is
      thought to facilitate transcriptional repression in yeast. Although this is
      particularly well characterized for telomeres, the molecular basis of their
      specific subnuclear organization is poorly understood. The use of live
      fluorescence imaging overcomes limitations of in situ staining on fixed cells and
      permits the analysis of chromatin dynamics in relation to stages of the cell
      cycle. RESULTS: We have characterized the dynamics of yeast telomeres and their
      associated domains of silent chromatin by using rapid time-lapse microscopy. In
      interphase, native telomeres are highly dynamic but remain within a restricted
      volume adjacent to the nuclear envelope. This constraint is lost during mitosis.
      A quantitative analysis of selected mutants shows that the yKu complex is
      necessary for anchoring some telomeres at the nuclear envelope (NE), whereas the
      myosin-like proteins Mlp1 and Mlp2 are not. We are able to correlate increased
      telomeric repression with increased anchoring and show that silent chromatin is
      tethered to the NE in a Sir-dependent manner in the absence of the yKu complex.
      Sir-mediated anchoring is S phase specific, while the yKu-mediated pathway
      functions throughout interphase. Subtelomeric elements of yeast telomere
      structure influence the relative importance of the yKu- and Sir-dependent
      mechanisms. CONCLUSIONS: Interphase positioning of telomeres can be achieved
      through two partially redundant mechanisms. One requires the heterodimeric yKu
      complex, but not Mlp1 and Mlp2. The second requires Silent information
      regulators, correlates with transcriptional repression, and is specific to S
      phase.

PMID- 12498683
TI  - Crosstalk between CARM1 methylation and CBP acetylation on histone H3.
AB  - BACKGROUND: Dynamic changes in the modification pattern of histones, such as
      acetylation, phosphorylation, methylation, and ubiquitination, are thought to
      provide a code for the correct regulation of gene expression mostly by affecting
      chromatin structure and interactions of non-histone regulatory factors with
      chromatin. Recent studies have suggested the existence of an interplay between
      histone modifications during transcription. The CBP/p300 acetylase and the CARM1
      methyltransferase can positively regulate the expression of estrogen-responsive
      genes, but the existence of a crosstalk between lysine acetylation and arginine
      methylation on chromatin has not yet been established in vivo. RESULTS: By
      following the in vivo pattern of modifications on histone H3, following estrogen
      stimulation of the pS2 promoter, we show that arginine methylation follows prior
      acetylation of H3. Within 15 min after estrogen stimulation, CBP is bound to
      chromatin, and acetylation of K18 takes place. Following these events, K23 is
      acetylated, CARM1 associates with chromatin, and methylation at R17 takes place.
      Exogenous expression of CBP is sufficient to drive the association of CARM1 with
      chromatin and methylation of R17 in vivo, whereas an acetylase-deficient CBP
      mutant is unable to induce these events. A mechanism for the observed cooperation
      between acetylation and arginine methylation comes from the finding that
      acetylation at K18 and K23, but not K14, tethers recombinant CARM1 to the H3 tail
      and allows it to act as a more efficient arginine methyltransferase. CONCLUSION:
      These results reveal an ordered and interdependent deposition of acetylation and
      arginine methylation during estrogen-regulated transcription and provide support
      for a combinatorial role of histone modifications in gene expression.

PMID- 12498684
TI  - Control of Lte1 localization by cell polarity determinants and Cdc14.
AB  - BACKGROUND: The putative guanine nucleotide exchange factor Lte1 plays an
      essential role in promoting exit from mitosis at low temperatures. Lte1 is
      thought to activate a Ras-like signaling cascade, the mitotic exit network (MEN).
      MEN promotes the release of the protein phosphatase Cdc14 from the nucleolus
      during anaphase, and this release is a prerequisite for exit from mitosis. Lte1
      is present throughout the cell during G1 but is sequestered in the bud during S
      phase and mitosis by an unknown mechanism. RESULTS: We show that anchorage of
      Lte1 in the bud requires septins, the cell polarity determinants Cdc42 and Cla4,
      and Kel1. Lte1 physically associates with Kel1 and requires Kel1 for its
      localization in the bud, suggesting a role for Kel1 in anchoring Lte1 at the bud
      cortex. Our data further implicate the PAK-like protein kinase Cla4 in
      controlling Lte1 phosphorylation and localization. CLA4 is required for Lte1
      phosphorylation and bud localization. Furthermore, when overexpressed, CLA4
      induces Lte1 phosphorylation and localization to regions of polarized growth.
      Finally, we show that Cdc14, directly or indirectly, controls Lte1
      dephosphorylation and delocalization from the bud during exit from mitosis.
      CONCLUSION: Restriction of Lte1 to the bud cortex depends on the cortical
      proteins Cdc42 and Kel1 and the septin ring. Cla4 and Cdc14 promote and demote
      Lte1 localization at and from the bud cortex, respectively, suggesting not only
      that the phosphorylation status of Lte1 controls its localization but also
      indicating that Cla4 and Cdc14 are key regulators of the spatial asymmetry of
      Lte1.

PMID- 12498686
TI  - The Cdc20 homolog, FZY-1, and its interacting protein, IFY-1, are required for
      proper chromosome segregation in Caenorhabditis elegans.
AB  - Accurate chromosome segregation is achieved by a series of highly regulated
      processes that culminate in the metaphase-to-anaphase transition of the cell
      cycle. In the budding yeast Saccharomyces cerevisiae, the degradation of the
      securin protein Pds1 reverses the binding and inhibition of the separase protein
      Esp1. Esp1 cleaves Scc1. That cleavage promotes the dissociation of the cohesin
      complex from the chromosomes and leads the separation of sister chromatids.
      Proteolysis of Pds1 is regulated by the anaphase-promoting complex (APC), a large
      multi-subunit E3 ubiquitin ligase whose activity is regulated by Cdc20/Fizzy. We
      have previously shown that the Caenorhabditis elegans genes mdf-1/MAD1 and mdf
      2/MAD2 encode key members of the spindle checkpoint. Loss of function of either
      gene leads to an accumulation of somatic and heritable defects and ultimately
      results in death. Here we show that a missense mutation in fzy-1/CDC20/Fizzy
      suppresses mdf-1 lethality. We identified a FZY-1-interacting protein, IFY-1, a
      novel destruction-box protein. IFY-1 accumulates in one-cell-arrested emb-30/APC4
      embryos and interacts with SEP-1, a C. elegans separase, suggesting that IFY-1
      functions as a C. elegans securin.

PMID- 12498685
TI  - The large GTPase dynamin associates with the spindle midzone and is required for
      cytokinesis.
AB  - Cytokinesis involves the concerted efforts of the microtubule and actin
      cytoskeletons as well as vesicle trafficking and membrane remodeling to form the
      cleavage furrow and complete daughter cell separation. The exact mechanisms that
      support membrane remodeling during cytokinesis remain largely undefined. In this
      study, we report that the large GTPase dynamin, a protein involved in membrane
      tubulation and vesiculation, is essential for successful cytokinesis. Using
      biochemical and morphological methods, we demonstrate that dynamin localizes to
      the spindle midzone and the subsequent intercellular bridge in mammalian cells
      and is also enriched in spindle midbody extracts. In Caenorhabditis elegans,
      dynamin localized to newly formed cleavage furrow membranes and accumulated at
      the midbody of dividing embryos in a manner similar to dynamin localization in
      mammalian cells. Further, dynamin function appears necessary for cytokinesis, as
      C. elegans embryos from a dyn-1 ts strain, as well as dynamin RNAi-treated
      embryos, showed a marked defect in the late stages of cytokinesis. These findings
      indicate that, during mitosis, conventional dynamin is recruited to the spindle
      midzone and the subsequent intercellular bridge, where it plays an essential role
      in the final separation of dividing cells.

PMID- 12498687
TI  - Lefty proteins are long-range inhibitors of squint-mediated nodal signaling.
AB  - The regulation of signaling pathways by feedback inhibitors has become an
      emerging theme in the control of pattern formation during development. Nodal and
      Lefty proteins belong to divergent subfamilies of the TGF-beta family. Nodal
      signals promote mesendoderm induction in vertebrates, and Lefty proteins
      antagonize it. In zebrafish, Squint functions as a long-range Nodal signal during
      mesoderm induction. We report that the range over which Squint induces mesoderm
      is reduced by Lefty proteins. In contrast, the activity range of the short-range
      Nodal signal Cyclops is not regulated by Lefty activity. We present three lines
      of evidence that Lefty proteins diminish the range of Squint signaling by acting
      not only as antagonists of Squint autoregulation but also as long-range
      inhibitors of Squint activity. First, Lefty can block Nodal signaling at a
      distance. Second, Lefty regulates the range of Squint signaling before regulating
      squint expression. Third, Lefty restricts the range of Squint activity in squint
      mutant embryos, in which the endogenous gene is not subject to autoregulation. We
      also find that Lefty restricts the response to both high and low levels of Nodal
      signaling. These results indicate that Lefty proteins restrict the activity range
      of Nodal signals by dampening Nodal signaling in surrounding cells.

PMID- 12498688
TI  - Lefty antagonism of Squint is essential for normal gastrulation.
AB  - Activities of a variety of signaling proteins that regulate embryogenesis are
      limited by endogenous antagonists. The zebrafish Nodal-related ligands, Squint
      and Cyclops, and their antagonists, Lefty1 and Lefty2, belong to the TGFbeta
      related protein superfamily, whose members have widespread biological activities.
      Among other activities, Nodals direct the formation of most mesendoderm. By
      inducing their own transcription and that of the Lefties, Nodal signals establish
      positive and negative autoregulatory loops. To investigate how these
      autoregulatory pathways regulate development, we depleted zebrafish embryos of
      Lefty1 and/or Lefty2 by using antisense morpholino oligonucleotides. Loss of
      Lefty1 causes aberrations during somitogenesis stages, including left-right
      patterning defects, whereas Lefty2 depletion has no obvious consequences.
      Depletion of both Lefty1 and Lefty2, by contrast, causes unchecked Nodal
      signaling, expansion of mesendoderm, and loss of ectoderm. The expansion of
      mesendoderm correlates with an extended period of rapid cellular internalization
      and a failure of deep-cell epiboly. The gastrulation defects of embryos depleted
      of Lefty1 and Lefty2 result from the deregulation of Squint signaling. In
      contrast, deregulation of Cyclops does not affect morphology or the transcription
      of Nodal target genes during gastrulation. Furthermore, we find that Cyclops is
      specifically required for the maintenance of lefty1 and lefty2 transcription.

PMID- 12498689
TI  - Lefty-dependent inhibition of Nodal- and Wnt-responsive organizer gene expression
      is essential for normal gastrulation.
AB  - During gastrulation, diffusible "organizer" signals, including members of the
      TGFbeta Nodal subfamily, pattern dorsal mesoderm and the embryonic axes.
      Simultaneously, negative regulators of these signals, including the Nodal
      inhibitor Lefty, an atypical TGFbeta factor, are induced by Nodal. This suggests
      that Lefty-dependent modulation of organizer signaling might regulate dorsal
      mesoderm patterning and axial morphogenesis. Here, Xenopus Lefty (Xlefty)
      function was blocked by injection of anti-Xlefty morpholino oligonucleotides
      (MO). Xlefty-deficient embryos underwent exogastrulation, an aberrant
      morphogenetic process not predicted from deregulation of the Nodal pathway alone.
      In the absence of Xlefty, both Nodal- (Xnr2, gsc, cer, Xbra) and Wnt-responsive
      (gsc, Xnr3) organizer gene expression expanded away from the dorsal blastopore
      lip. Conversely, coexpression of Xlefty with Nodal or Wnt reduced the ectopic
      expression of Nodal- (Xbra) and Wnt-responsive (Xnr3) genes in a dose-dependent
      manner. Furthermore, Xlefty expression in the ectodermal animal pole inhibited
      endogenous Nodal- and Wnt-responsive gene expression in distant mesoderm cells,
      indicating that Xlefty inhibition can spread from its source. We hypothesize that
      Xlefty negatively regulates the spatial extent of Nodal- and Wnt-responsive gene
      expression in the organizer and that this Xlefty-dependent inhibition is
      essential for normal organizer patterning and gastrulation.

PMID- 12498690
TI  - The cell cycle regulatory factor TAF1 stimulates ribosomal DNA transcription by
      binding to the activator UBF.
AB  - Control of ribosome biogenesis is a potential mechanism for the regulation of
      cell size during growth, and a key step in regulating ribosome production is
      ribosomal RNA synthesis by RNA polymerase I (Pol I). In humans, Pol I
      transcription requires the upstream binding factor UBF and the selectivity factor
      SL1 to assemble coordinately on the promoter. UBF is an HMG box-containing factor
      that binds to the rDNA promoter and activates Pol I transcription through its
      acidic carboxy-terminal tail. Using UBF (284-670) as bait in a yeast two-hybrid
      screen, we have identified an interaction between UBF and TAF1, a factor involved
      in the transcription of cell cycle and growth regulatory genes.
      Coimmunoprecipitation and protein-protein interaction assays confirmed that TAF1
      binds to UBF. Confocal microscopy showed that TAF1 colocalizes with UBF in Hela
      cells, and cell fractionation experiments provided further evidence that a
      portion of TAF1 is localized in the nucleolus, the organelle devoted to ribosomal
      DNA transcription. Cotransfection and in vitro transcription assays showed that
      TAF1 stimulates Pol I transcription in a dosage-dependent manner. Thus, TAF1 may
      be involved in the coordinate expression of Pol I- and Pol II-transcribed genes
      required for protein biosynthesis and cell cycle progression.

PMID- 12498691
TI  - Neural processing of auditory looming in the human brain.
AB  - Acoustic intensity change, along with interaural, spectral, and reverberation
      information, is an important cue for the perception of auditory motion.
      Approaching sound sources produce increases in intensity, and receding sound
      sources produce corresponding decreases. Human listeners typically overestimate
      increasing compared to equivalent decreasing sound intensity and underestimate
      the time to contact of approaching sound sources. These characteristics could
      provide a selective advantage by increasing the margin of safety for response to
      looming objects. Here, we used dynamic intensity and functional magnetic
      resonance imaging to examine the neural underpinnings of the perceptual priority
      for rising intensity. We found that, consistent with activation by horizontal and
      vertical auditory apparent motion paradigms, rising and falling intensity
      activated the right temporal plane more than constant intensity. Rising compared
      to falling intensity activated a distributed neural network subserving space
      recognition, auditory motion perception, and attention and comprising the
      superior temporal sulci and the middle temporal gyri, the right temporoparietal
      junction, the right motor and premotor cortices, the left cerebellar cortex, and
      a circumscribed region in the midbrain. This anisotropic processing of acoustic
      intensity change may reflect the salience of rising intensity produced by looming
      sources in natural environments.

PMID- 12498692
TI  - An unusual cation channel mediates photic control of locomotion in Drosophila.
AB  - A unique family of putative ion channels that are related to voltage-gated sodium
      and calcium channels has been identified in genomic and cDNA studies of
      metazoans. Aside from evidence for expression of family members in the nervous
      system, little is known about the operation of the channel or its functional
      significance. In the present study, this conserved family's sole Drosophila
      member, a gene known both as CG1517 and as Dmalpha1U, is shown to correspond to
      the narrow abdomen (na) gene and is the locus of a set of mutations that affect
      sensitivity to anesthetics. Immunohistochemistry of adult heads reveals that the
      channel is expressed in the neuropil of the central complex and optic lobe;
      expression is severely depressed in the mutants. In addition to previously
      described defects, the mutant phenotype is demonstrated here to include
      dysfunction in the coupling between light and locomotor behavior. Most
      dramatically, mutant flies have an inversion of relative locomotor activity in
      light versus dark. The involvement of the channel in daily rhythms of the fruit
      fly is especially provocative because the human ortholog lies in a candidate
      region linked to bipolar disorder, a disease frequently associated with altered
      diurnal behavior.

PMID- 12498693
TI  - Gene-specific targeting of H3K9 methylation is sufficient for initiating
      repression in vivo.
AB  - Covalent modifications of chromatin have emerged as key determinants of the
      genome's transcriptional competence. Histone H3 lysine 9 (H3K9) methylation is an
      epigenetic signal that is recognized by HP1 and correlates with gene silencing in
      a variety of organisms. Discovery of the enzymes that catalyze H3K9 methylation
      has identified a second gene-specific function for this modification in
      transcriptional repression. Whether H3K9 methylation is causative in the
      initiation and establishment of gene repression or is a byproduct of the process
      leading to the repressed state remains unknown. To investigate the role of HMTs
      and specifically H3K9 methylation in gene repression, we have employed engineered
      zinc-finger transcription factors (ZFPs) to target HMT activity to a specific
      endogenous gene. By utilizing ZFPs that recognize the promoter of the endogenous
      VEGF-A gene, and thus employing this chromosomal locus as an in vivo reporter, we
      show that ZFPs linked to a minimal catalytic HMT domain affect local methylation
      of histone H3K9 and the consequent repression of target gene expression.
      Furthermore, amino acid substitutions within the HMT that ablate its catalytic
      activity effectively eliminate the ability of the ZFP fusions to repress
      transcription. Thus, H3K9 methylation is a primary signal that is sufficient for
      initiating a gene repression pathway in vivo.

PMID- 12498694
TI  - Hapmap flap.

PMID- 12498695
TI  - Cloned cattle controversy.

PMID- 12498696
TI  - Down but not out.

PMID- 12498697
TI  - Prize divide.

PMID- 12498698
TI  - Kin selection.

PMID- 12498699
TI  - Retinal function: coupling cones clarifies vision.
AB  - Gap junctions have been shown to electrically couple cone photoreceptors:
      coupling blurs the image coded by cones, but this loss is offset by a decrease in
      noise. Electrical coupling thus improves the resolution of signals distributed
      across groups of cells.

PMID- 12498700
TI  - Drosophila oogenesis: generating an axis of polarity.
AB  - New studies of moesin function during Drosophila oogenesis show that Dmoesin
      tethers actin to the oocyte membrane. Interestingly, Dmoesin and an intact cortex
      are also required to stabilise ooycte polarity.

PMID- 12498701
TI  - Color vision: how the cortex represents color.
AB  - Our understanding of how we see color has benefited from the long tradition of
      visual psychophysics. More recently, models and methods from psychophysics are
      guiding modern neuroimaging experiments on color vision. Combining the two
      techniques can lead to discoveries that neither can make alone.

PMID- 12498702
TI  - Photoperiodism: the coincidental perception of the season.
AB  - Many plants use the seasonal change in daylength as a signal for flowering.
      Daylength sensing in Arabidopsis has now been shown to occur by an external
      coincidence mechanism, which operates by the circadian and light regulation of
      CONSTANS.

PMID- 12498703
TI  - Chloroplast division: a work of ARTEMIS.
AB  - Chloroplasts contain three membrane systems that constrict together during
      division of the organelle. A newly identified protein, ARTEMIS, may shed light on
      the nuclear control of chloroplast division, and also on the mechanism of
      thylakoid membrane fission and how this is coordinated with fission of the two
      envelope membranes.

PMID- 12498704
TI  - DNA repair: bioinformatics helps reverse methylation damage.
AB  - Recent work has uncovered a novel DNA repair enzyme: the AlkB protein of
      Escherichia coli, which oxidises the methyl groups of 1-methyladenine and 3
      methylcytosine to hydroxymethyl moieties; the oxidised groups are subsequently
      released as formaldehyde, regenerating the unmodified bases.

PMID- 12498705
TI  - Olfactory axons: a remarkable convergence.
AB  - Thousands of neurons expressing a given mouse odorant receptor project to a few
      glomeruli in the olfactory bulb. New observations on mice expressing small
      odorant receptor transgenes provide support for the idea that interdependence is
      involved in the maturation of this remarkable convergence.

PMID- 12498706
TI  - RNA interference: the fragile X syndrome connection.
AB  - Fragile X syndrome is caused by loss of expression of FMRP, a protein proposed to
      act as a regulator of mRNA translation which promotes synaptic maturation and
      function. Now FMRP has been found to associate with the RNP complex that mediates
      post-transcriptional silencing by RNAi.

PMID- 12498707
TI  - Polyadenylation: a tail of two complexes.
AB  - Recent studies have uncovered new connections between the enzymes of mRNA 3' end
      processing and RNA polymerase II. These connections improve the efficiency of
      polyadenylation and signal to the polymerase to terminate transcription; their
      discovery reveals another level of gene regulation.

PMID- 12498708
TI  - A putative link between exocytosis and tumor development.
AB  - Desmoplastic small round cell tumor (DSRCT) is characterized by a
      t(11;22)(p13;q12) translocation breakpoint. In this issue of Cancer Cell, now
      show that the resulting EWS-WT1 gene-fusion product leads to overexpression of
      BAIAP3, a protein implicated in regulated exocytosis.

PMID- 12498709
TI  - Vaccination against tumor neovascularization: Promise and reality.
AB  - Immunization against angiogenic-associated antigens selectively expressed on
      tumor vasculature provides for a novel strategy to block tumor growth. The
      feasibility of this approach has recently been borne out in several reports
      demonstrating that the protein or DNA of angiogenic molecules, such as VEGF-R2,
      can be used as vaccines to generate an effective cytotoxic T cell and antibody
      response against tumor vessels, thereby blocking tumor growth and metastasis.

PMID- 12498710
TI  - Is NF-kappaB2/p100 a direct activator of programmed cell death?
AB  - Transcription factor NF-kappaB has been implicated in cancer development due to
      its ability to upregulate expression of genes with potentially prooncogenic
      functions, such as cell cycle regulators and antiapoptotic proteins (Karin et
      al., 2002). A recent report by suggests that a structural motif, a death domain
      (DD), present in one of the mammalian NF-kappaB proteins, NF-kappaB2/p100, allows
      it to directly activate cell death in a transcription-independent manner.
      Further, it is suggested that loss of the proapoptotic function of NF
      kappaB2/p100 is directly linked to its oncogenic activity in lymphomas.

PMID- 12498711
TI  - p53: regular or super?
AB  - Increased p53 expression under the endogenous promoter protects "super p53" mice
      from tumorigenesis without the undesirable effects of premature aging.

PMID- 12498712
TI  - Acute leukemia: a pediatric perspective.
AB  - The spectrum of hematological malignancies differs markedly between children and
      adults. Moreover, diseases such as acute lymphoblastic leukemia, acute myeloid
      leukemia, and myelodysplastic syndrome also demonstrate distinct biologic
      features and responses to treatment between these populations. In this review, we
      summarize our current understanding of the molecular pathology of acute leukemia
      and myelodysplastic syndrome, emphasizing areas in which studies in pediatric
      patients are providing unique insights into the hematopoietic malignancies of
      adults.

PMID- 12498713
TI  - Focus on embryonal malignancies.

PMID- 12498714
TI  - Conditional activation of Neu in the mammary epithelium of transgenic mice
      results in reversible pulmonary metastasis.
AB  - To determine the impact of tumor progression on the reversibility of Neu-induced
      tumorigenesis, we have used the tetracycline regulatory system to conditionally
      express activated Neu in the mammary epithelium of transgenic mice. When induced
      with doxycycline, bitransgenic MMTV-rtTA/TetO-NeuNT mice develop multiple
      invasive mammary carcinomas, essentially all of which regress to a clinically
      undetectable state following transgene deinduction. This demonstrates that Neu
      initiated tumorigenesis is reversible. Strikingly, extensive lung metastases
      arising from Neu-induced mammary tumors also rapidly and fully regress following
      the abrogation of Neu expression. However, despite the near universal dependence
      of both primary tumors and metastases on Neu transgene expression, most animals
      bearing fully regressed Neu-induced tumors ultimately develop recurrent tumors
      that have progressed to a Neu-independent state.

PMID- 12498715
TI  - E2F4 loss suppresses tumorigenesis in Rb mutant mice.
AB  - The E2F transcription factors mediate the activation or repression of key cell
      cycle regulatory genes under the control of the retinoblastoma protein (pRB)
      tumor suppressor and its relatives, p107 and p130. Here we investigate how E2F4,
      the major "repressive" E2F, contributes to pRB's tumor-suppressive properties.
      Remarkably, E2F4 loss suppresses the development of both pituitary and thyroid
      tumors in Rb(+/-) mice. Importantly, E2F4 loss also suppresses the inappropriate
      gene expression and proliferation of pRB-deficient cells. Biochemical analyses
      suggest that this tumor suppression occurs via a novel mechanism: E2F4 loss
      allows p107 and p130 to regulate the pRB-specific, activator E2Fs. We also detect
      these novel E2F complexes in pRB-deficient cells, suggesting that they play a
      significant role in the regulation of tumorigenesis in vivo.

PMID- 12498716
TI  - Id1 regulates angiogenesis through transcriptional repression of thrombospondin
      1.
AB  - Id proteins are helix-loop-helix transcription factors that regulate tumor
      angiogenesis. In order to identify downstream effectors of Id1 involved in the
      regulation of angiogenesis, we performed PCR-select subtractive hybridization on
      wild-type and Id1 knockout mouse embryo fibroblasts (MEFs). Here we demonstrate
      that thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, is a target of
      transcriptional repression by Id1. We also show that Id1-null MEFs secrete an
      inhibitor of endothelial cell migration, which is completely inactivated by
      depletion of TSP-1. Furthermore, in vivo studies revealed decreased
      neovascularization in matrigel assays in Id1-null mice compared to their wild
      type littermates. This decrease was completely reversed by a TSP-1 neutralizing
      antibody. We conclude that TSP-1 is a major target for Id1 effects on
      angiogenesis.

PMID- 12498717
TI  - Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in
      esophageal squamous cell carcinoma.
AB  - We performed a comprehensive survey of commonly inactivated tumor suppressor
      genes in esophageal squamous cell carcinoma (ESCC) based on functional
      reactivation of epigenetically silenced tumor suppressor genes by 5-aza-2'
      deoxycytidine and trichostatin A using microarrays containing 12599 genes. Among
      58 genes identified by this approach, 44 (76%) harbored dense CpG islands in the
      promoter regions. Thirteen of twenty-two tested gene promoters were methylated in
      cell lines, and ten in primary ESCC accompanied by silencing at the mRNA level.
      Potent growth suppressive activity of three genes including CRIP-1,
      Apolipoprotein D, and Neuromedin U in ESCC cells was demonstrated by colony focus
      assays. Pharmacologic reversal of epigenetic silencing is a powerful approach for
      comprehensive identification of tumor suppressor genes in human cancers.

PMID- 12498718
TI  - Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated
      exocytosis in tumorigenesis.
AB  - Desmoplastic small round cell tumor (DSRCT) is defined genetically by the
      chimeric fusion of the Ewing's sarcoma and Wilms' tumor genes, generating a novel
      transcription factor, EWS-WT1. By using cells with inducible EWS-WT1 to screen
      high-density microarrays, we identified BAIAP3 as a transcriptional target of the
      chimera. The BAIAP3 promoter is specifically bound in vivo by the (-KTS) isoform
      of EWS-WT1, consistent with its activation in reporter assays. BAIAP3 encodes a
      protein implicated in regulated exocytosis, which is colocalized with a secreted
      growth factor within cytoplasmic organelles. Ectopic expression of BAIAP3 in
      tumor cells dramatically enhances growth in low serum and colony formation in
      soft agar. BAIAP3 therefore encodes a transcriptional target of an oncogenic
      fusion protein that implicates the regulated exocytotic pathway in cancer cell
      proliferation.

PMID- 12498719
TI  - Hyperactivation of protein kinase B and ERK have discrete effects on survival,
      proliferation, and cytokine expression in Nf1-deficient myeloid cells.
AB  - The Nf1 tumor suppressor encodes a GTPase-activating protein for Ras. Previous
      work has implicated hyperactive Ras in the aberrant growth of Nf1-deficient
      cells; however, there are limited data on which effectors modulate specific
      phenotypes. To address this, we generated myeloid cell lines by infecting fetal
      liver cells with a retrovirus encoding a truncated allele of c-Myb. Granulocyte
      macrophage colony stimulating factor (GM-CSF) promoted the survival of wild-type
      Myb cells in a dose-dependent manner. By contrast, Nf1-deficient myeloid cells
      deprived of growth factors, were resistant to apoptosis due to hyperactivation of
      the phosphoinositide-3-OH kinase/protein kinase B cascade. Nf1(-/-) cells also
      demonstrated growth factor-independent proliferation and upregulation of GM-CSF
      mRNA production that were dependent upon Raf/MEK/ERK signaling. These data link
      specific Ras effectors with discrete cellular phenotypes in Nf1-deficient cells.

PMID- 12498721
TI  - Linking Chinese medicine and G-protein-coupled receptors.
AB  - Following the purification of the immunosuppressant ISP-1 from a Chinese
      medicine, Japanese scientists have developed a more potent immune modulator,
      FTY720, that induces T-cell homing. FTY720, a promising immunosuppressant for use
      in patients with tissue transplants and autoimmune diseases, is currently in
      clinical trials. Two recent studies have elucidated that the mechanism of action
      of FTY720 is via a subset of G-protein-coupled receptors for the lysophospholipid
      mediator sphingosine-1-phosphate.

PMID- 12498722
TI  - Correlation between affinity and efficacy.

PMID- 12498724
TI  - Therapeutic vaccination for spinal cord injury: helping the body to cure itself.
AB  - Inflammation is thought to exacerbate the outcome of spinal cord injury. However,
      our findings have led us to view inflammation as a healing response that needs
      the help of a systemic immune response mediated by T helper 1 (Th1) cells that
      are specific to the abundant antigens residing in the lesion site. Strains differ
      in their ability to manifest, at the right time and intensity, a spontaneous T
      cell response to antigens at the lesion site and therefore in their ability to
      generate a local inflammatory response whose outcome is beneficial (maintenance
      and repair). All strains, however, can benefit from immune intervention that
      boosts and regulates the inflammatory response. Because recovery comprises multi
      step processes, pharmacological intervention will be less effective than well
      synchronized, self-healing immune activity. Risk-free neuroprotective
      intervention might be achieved by post-traumatic vaccination with a weak, non
      pathogenic, auto-antigen, causing autoimmune T cells to home to the lesion site
      where they become activated and therefore activate local phagocytic cells to
      remove hostile elements and provide growth factors.

PMID- 12498725
TI  - Manipulating neuroinflammatory reactions in the injured spinal cord: back to
      basics.
AB  - Recruitment of inflammatory leukocytes to the injured spinal cord is a
      physiological response that is associated with the production of cytokines and
      proteinases that are involved in host defense and wound repair. Cells in the
      spinal cord are mainly post-mitotic and tissue regeneration is poor; thus, these
      inflammatory mediators can exacerbate the damage to spared tissue and thereby
      impair spontaneous functional recovery. Although several aspects of immune
      function might benefit the CNS, experimental studies indicate that acute
      neuroinflammation aggravates tissue injury. Until the timing and nature of the
      molecular signals that govern leukocyte recruitment and activation after spinal
      injury are defined, clinical therapies designed to boost immune cell function
      should be avoided.

PMID- 12498726
TI  - Neurological disease: UPS stops delivering!
AB  - The ubiquitin-proteasome system (UPS) plays a vital role in directing molecules
      to the 26S proteasome for degradation as well as other locales in the cell.
      Disrupting UPS function can lead to the aggregation of mutant or misfolded
      proteins, which disrupts normal cellular activity in diverse ways. Here we
      discuss how UPS dysfunction might contribute to a variety of neurological
      problems.

PMID- 12498727
TI  - Regulation of endothelium-derived vasoactive autacoid production by hemodynamic
      forces.
AB  - Endothelial cells, which are situated at the interface between blood and the
      vessel wall, have a crucial role in controlling vascular tone and homeostasis,
      particularly in determining the expression of pro-atherosclerotic and anti
      atherosclerotic genes. Many of these effects are mediated by changes in the
      generation and release of endothelium-derived autacoids [from the Greek autos
      (self) and akos (remedy)], which are generally short-lived and locally acting. In
      vivo, endothelial cells are constantly subjected to mechanical stimulation, which
      in turn determines the acute production of autacoids and the levels of autacoid
      producing enzymes.

PMID- 12498728
TI  - Emerging roles for orphan G-protein-coupled receptors in the cardiovascular
      system.
AB  - Despite current drug therapies, including those that target enzymes, channels and
      known G-protein-coupled receptors (GPCRs), cardiovascular disease remains the
      major cause of ill health, which suggests that other transmitter systems might be
      involved in this disease. In humans, approximately 175 genes have been predicted
      to encode 'orphan' GPCRs, where the endogenous ligand is not yet known. As a
      result of intensive screening using 'reverse pharmacology', an increasing number
      of orphan receptors are being paired with their cognate ligands, many of which
      are peptides. The existence of some of these peptides such as urotensin-II and
      relaxin had been known for some time but others, including ghrelin and apelin,
      represent novel sequences. The pharmacological characterization of these emerging
      peptide-receptor systems is a tantalising area of cardiovascular research, with
      the prospect of identifying new therapeutic targets.

PMID- 12498729
TI  - Rhodopsin crystal: new template yielding realistic models of G-protein-coupled
      receptors?
AB  - Molecular modelling is of major help to understand structure-function data on G
      protein-coupled receptors (GPCRs). Since the first determination of the structure
      of rhodopsin, at high resolution, the view has emerged that it will be now easy
      to automatically obtain realistic models for any GPCR by homology modeling. Our
      experience on cholecystokinin CCK(1) receptor modelling together with available
      data on other GPCRs leads us to rule out this opinion. We believe that
      construction of realistic models of certain GPCRs still remains time-consuming
      and requires many refinements of the models in close association with
      experiments. This conclusion has important consequences for modelling orphan
      GPCRs.

PMID- 12498730
TI  - Techniques: fruit flies as models for neuropharmacological research.
AB  - An unlikely animal model is gaining popularity in neuropharmacological research:
      the 2-mm fruit fly (Drosophila melanogaster). Drugs have been administered to
      adult flies in their food and, more recently, via gasses and injections.
      Pharmacological tools have introduced behavioral alterations in Drosophila
      reminiscent of human behavior, rescued flies from gene-alteration-triggered
      neuropathologies, and triggered gene silencing. Combined, these methods hold
      promise for significant neuropharmacological advancement.

PMID- 12498731
TI  - Techniques: applications of the nerve-bouton preparation in neuropharmacology.
AB  - Single mammalian neurons can be isolated with adherent functional synaptic
      terminals using an enzyme-free, mechanical dissociation procedure. This allows
      investigations of the effects of presynaptic modulators of synaptic transmission
      with unprecedented ease and accuracy. Furthermore, single presynaptic terminals
      and boutons can be visualized using fluorescent markers and can also be focally
      stimulated with electrical pulses. In this article, the isolated-nerve-adherent
      synaptic-bouton preparation and some examples of its general properties and uses
      are discussed.

PMID- 12498732
TI  - Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding
      study with female B6C3F(1) mice.
AB  - Fumonisinmycotoxins are produced by Fusaria fungi that grow worldwide primarily
      on corn. Fumonisin B(1), the most predominant form in corn samples, is a renal
      carcinogen in male F344/N rats and a hepatocarcinogen in female B6C3F(1) mice
      when fed at concentrations higher than 50 ppm (70 micromol/kg) in the diet for 2
      years. We sought to determine the relative toxicities of several naturally
      occurring fumonisin derivatives when included in the diet of female B6C3F(1)
      mice. Mice were fed diets containing fumonisin B(1), fumonisin B(2), fumonisin
      B(3), fumonisin P1, hydrolyzed-fumonisin B(1), N-(acetyl)fumonisin B(1), or N
      (carboxymethyl)fumonisin B(1) (approximately 0, 14, 70, and 140 micromol/kg diet)
      for 28 days. None of the doses used caused a decrease in body weight gain over
      the 28 days. Serum levels of total bile acids, cholesterol, and alkaline
      phosphatase were increased only in mice receiving 72 and 143 micromol/kg
      fumonisin B(1), suggesting that only fumonisin B(1) was hepatotoxic in the mice.
      Corroborating this observation, the liver weight, relative to body weight, was
      decreased only in the mice that consumed 143 micromol/kg fumonisin B(1).
      Consistent with fumonisin B(1) inhibition of ceramide synthase, the liver
      sphinganine-to-sphingosine ratio was increased and the liver ceramide levels were
      decreased only in the mice receiving 72 and 143 micromol/kg fumonisin B(1).
      Increased hepatocellular apoptosis, hepatocellular hypertrophy, Kupffer cell
      hyperplasia, and macrophage pigmentation were detected in the mice consuming 72
      and 143 micromol/kg fumonisin B(1). The other fumonisin derivatives did not alter
      serum analytes, organ weights, or hepatic structure. These results suggest that,
      of the naturally occurring fumonisins, fumonisin B(1) is the principal
      hepatotoxic derivative in the B6C3F(1) mouse.

PMID- 12498733
TI  - Effects of P-glycoprotein inhibitors on cadmium accumulation in cultured renal
      epithelial cells, LLC-PK1, and OK.
AB  - The purpose of this study was to investigate whether cadmium (Cd) efflux across
      the apical membrane of cultured renal epithelial cells, LLC-PK(1) and OK, is
      mediated via P-glycoprotein (P-gp). These cells were preincubated for 30 min with
      a typical P-gp inhibitor such as verapamil, diltiazem, nifedipine, vinblastine,
      or cyclosporin A before the incubation with 1 microM (109)CdCl(2) for 15 min.
      Preincubation with each P-gp inhibitor significantly increased Cd accumulation in
      LLC-PK(1), and OK cells. Treatment of these cells with UIC2, a P-gp monoclonal
      antibody, also significantly increased Cd accumulation in these cells. Thus, the
      pretreatment of cells with P-gp inhibitor appears to increase Cd accumulation as
      a result of the inhibition of Cd efflux via P-gp. To confirm Cd efflux via P-gp,
      Cd accumulation in P-gp-overexpressed cells (LLC-GA5-COL150 cells) was compared
      with that in parental LLC-PK(1) cells. LLC-GA5-COL150 cells accumulated less Cd
      than did LLC-PK(1) cells, and the effects of the P-gp inhibitors and UIC2 on Cd
      accumulation were greater in LLC-GA5-COL150 cells. These results suggest that P
      gp in LLC-PK(1) and OK cells appear to act as an efflux pump of Cd, decreasing
      cellular Cd accumulation.

PMID- 12498734
TI  - Cytotoxic effect of peroxisome proliferator fenofibrate on human HepG2 hepatoma
      cell line and relevant mechanisms.
AB  - The aim of this work was to investigate the effects of hypolipidemic agent
      fenofibrate (FF), a peroxisome proliferator (PP), on human HepG2 cells and to
      characterize the intracellular events involved. The results showed that, in
      contrast to the tumor-promoting effects in rodents, high FF concentrations
      induced human HepG2 cell death through a mechanism involving an increase in the
      levels of reactive oxygen species (ROS) and intracellular GSH depletion, which
      led, through mitochondrial dysfunction and perturbation of intracellular Ca(2+)
      homeostasis, to cell death. The nuclear receptor peroxisome proliferator
      activated receptor-alpha (PPAR(alpha)) was expressed following FF treatment. The
      results suggest that, although long-term administration of PPs causes liver
      cancer in susceptible species (e.g., rodents), FF inhibits the growth of human
      HepG2 cells in a dose-related manner and oxidative stress was involved in this
      effect.

PMID- 12498735
TI  - Gene expression changes induced in mouse liver by di(2-ethylhexyl) phthalate.
AB  - Increasing chemical use necessitates a better understanding of how pollutants,
      such as di(2-ethylhexyl) phthalate (DEHP), a peroxisome proliferator and a
      phthalate plasticizer, affect human health. To understand the effects of DEHP
      exposure, we utilized microarray technology to identify novel DEHP targets in
      livers of male C57BL/6 mice treated with 1.0% dietary DEHP for 13 weeks. We
      identified 51 DEHP-regulated genes; these genes are involved in, but not limited
      to, peroxisome proliferation, xenobiotic detoxification, oxidative stress
      response, immune function, steroid hormone metabolism, testis development, and
      pheromone transport. The reproductive toxicity mechanism of DEHP may be due to
      its effects on steroid hormone metabolism and sexual development. Confirmation of
      microarray results with Northern blots demonstrated that both low- and high-dose
      DEHP treatments altered the expression of genes associated with testis
      development and steroid hormone synthesis. Vanin-1, a regulator of testis
      development, was upregulated after exposure to 0.2 and 1.0% DEHP by 1.8- and 2.9
      fold, respectively. Several genes involved in hormone metabolism were also
      regulated by DEHP. 11betaHSDI was downregulated 1.8- and 3.1-fold by 0.2 and 1.0%
      DEHP, respectively, while HSD3b5 was suppressed similarly by 0.2% DEHP, 1.5-fold,
      and more severely by 1.0% DEHP, 8.0-fold. Interestingly, food restriction had a
      similar effect to DEHP on several genes, including HSD3b5. In addition,
      steroidogenic gene cyp7B1 was downregulated while phospholipid transfer protein
      and cyp2B9 were induced. Genes peripherally associated with steroid hormones were
      also affected: ALDH3, GSTtheta2, and Id2. Collectively, our data validate the
      concern for DEHP as a reproductive developmental toxicant.

PMID- 12498736
TI  - Altered protein profile and possible hypoxia in the placenta of 2,3,7,8
      tetrachlorodibenzo-p-dioxin-exposed rats.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy causes
      fetal death in many animal species. In an earlier study we observed alteration of
      placental glucose kinetics at the same TCDD exposure level that resulted in fetal
      death (Ishimura et al., Toxicol. Appl. Pharmacol. 178, 161-171, 2002). In the
      present study, in order to identify the molecules that might explain the
      alterations of placental function and the mechanism of fetal death, we used two
      dimensional gel electrophoresis (2D/E) to detect and identify placental proteins
      whose amounts changed after exposure to TCDD and we examined the expression
      properties of these proteins in the placenta during hypoxia by using the uterine
      artery ligation model. Pregnant Holtzman rats were given a single oral dose of
      1600 ng TCDD/kg body wt or an equivalent volume of vehicle (control) on
      gestational day (GD) 15 and placental tissue was collected on GD16 and GD20. The
      15,000 g supernatant fractions of placental homogenates from the control group
      and TCDD-exposed group were subjected to the 2D/E analysis, and the protein spots
      whose amounts had changed after exposure to TCDD were characterized by amino acid
      sequence analysis. The amounts of heat shock protein 27 (Hsp27) and beta
      tropomyosin (beta-TM) in TCDD-exposed placentas tended to have increased on GD16
      and had increased significantly on GD20, and these changes were followed by an
      approximately twofold increase in glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH) on GD20. Next, the uterine-artery ligation model was prepared on GD15,
      and the hypoxic placentas were collected on GD20. Two-D/E analysis of the 15,000
      g supernatant proteins of the placentas revealed an increased level of GAPDH but
      not of other proteins, including Hsp27 and beta-TM. The results of this study
      showed that the increase in GAPDH level during hypoxia previously observed in
      endothelial cells occurs in the placenta and indicated that the TCDD-exposed
      placentas were in a hypoxic state at the end of pregnancy. Finally, the results
      of this study suggested the possibility that the increased incidence of fetal
      death after exposure to TCDD was due to the placental hypoxia.

PMID- 12498737
TI  - Presence and regulation of metallothioneins in peripheral blood leukocytes of
      grey seals.
AB  - Heavy metal residues have been reported at high levels in marine mammals.
      Although the immunotoxicity of these contaminants has been demonstrated in
      laboratory models, evaluation of their potential immunotoxicity for human and
      wildlife species is complicated by variables that modulate the immune response
      and the immunotoxic effects of xenobiotics under field conditions.
      Metallothioneins (MT) modulate the bioavaibility of physiological cations and the
      toxicity of heavy metals. Moreover, these proteins have been demonstrated to
      modulate immune functions. In the present study, we demonstrated a rapid and
      sustained increase of transcripts of the two major isoforms of MT (MT-1 and MT-2)
      in grey seal peripheral blood leukocytes (PBL) exposed in vitro to Zn. This
      increase in mRNA corresponds to an increase of MT proteins in PBL. However, we
      demonstrated a high heterogeneity among the three major PBL subpopulations
      (granulocytes, lymphocytes and monocytes). Monocytes appear to be the most
      sensitive cells to Zn or Cd exposure. Intracellular MT levels in PBL
      subpopulations were dependent not only on the duration of exposure and the
      concentration, but also on the metal species. Cd was more potent than Zn as an
      inducer of MT in lymphocytes but not in monocytes. Moreover, grey seal peripheral
      blood lymphocytes are less sensitive to Cd exposure than human lymphocytes. This
      noninvasive approach helps to better assess the risk of heavy metal exposure by
      considering the potential role of MT as modulators of immune response.

PMID- 12498738
TI  - Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy.
AB  - Several cytopathic mechanisms have been suggested to mediate the dose-limiting
      cumulative and irreversible cardiomyopathy caused by doxorubicin. Recent evidence
      indicates that oxidative stress and mitochondrial dysfunction are key factors in
      the pathogenic process. The objective of this investigation was to test the
      hypothesis that carvedilol, a nonselective beta-adrenergic receptor antagonist
      with potent antioxidant properties, protects against the cardiac and hepatic
      mitochondrial bioenergetic dysfunction associated with subchronic doxorubicin
      toxicity. Heart and liver mitochondria were isolated from rats treated for 7
      weeks with doxorubicin (2 mg/kg sc/week), carvedilol (1 mg/kg ip/week), or the
      combination of the two drugs. Heart mitochondria isolated from doxorubicin
      treated rats exhibited depressed rates for state 3 respiration (336 +/- 26 versus
      425 +/- 53 natom O/min/mg protein) and a lower respiratory control ratio (RCR)
      (4.3 +/- 0.6 versus 5.8 +/- 0.4) compared with cardiac mitochondria isolated from
      saline-treated rats. Mitochondrial calcium-loading capacity and the activity of
      NADH-dehydrogenase were also suppressed in cardiac mitochondria from doxorubicin
      treated rats. Doxorubicin treatment also caused a decrease in RCR for liver
      mitochondria (3.9 +/- 0.9 versus 5.6 +/- 0.7 for control rats) and inhibition of
      hepatic cytochrome oxidase activity. Coadministration of carvedilol decreased the
      extent of cellular vacuolization in cardiac myocytes and prevented the inhibitory
      effect of doxorubicin on mitochondrial respiration in both heart and liver.
      Carvedilol also prevented the decrease in mitochondrial Ca(2+) loading capacity
      and the inhibition of the respiratory complexes of heart mitochondria caused by
      doxorubicin. Carvedilol by itself did not affect any of the parameters measured
      for heart or liver mitochondria. It is concluded that this protection by
      carvedilol against both the structural and functional cardiac tissue damage may
      afford significant clinical advantage in minimizing the dose-limiting
      mitochondrial dysfunction and cardiomyopathy that accompanies long-term
      doxorubicin therapy in cancer patients.

PMID- 12498739
TI  - Cytokine profiling and chemical allergy.

PMID- 12498741
TI  - fMRI retinotopic mapping--step by step.
AB  - fMRI retinotopic mapping provides detailed information about the correspondence
      between the visual field and its cortical representation in the individual
      subject. Besides providing for the possibility of unambiguously localizing
      functional imaging data with respect to the functional architecture of the visual
      system, it is a powerful tool for the investigation of retinotopic properties of
      visual areas in the healthy and impaired brain. fMRI retinotopic mapping differs
      conceptually from a more traditional volume-based, block-type, or event-related
      analysis, in terms of both the surface-based analysis of the data and the phase
      encoded paradigm. Several methodological works related to fMRI retinotopic
      mapping have been published. However, a detailed description of all the methods
      involved, discussing the steps from stimulus design to the processing of phase
      data on the surface, is still missing. We describe here step by step our
      methodology for the complete processing chain. Besides reusing methods proposed
      by other researchers in the field, we introduce original ones: improved stimuli
      for the mapping of polar angle retinotopy, a method of assigning volume-based
      functional data to the surface, and a way of weighting phase information
      optimally to account for the SNR obtained locally. To assess the robustness of
      these methods we present a study performed on three subjects, demonstrating the
      reproducibility of the delineation of low order visual areas.

PMID- 12498742
TI  - Steady-state visually evoked potential topography during processing of emotional
      valence in healthy subjects.
AB  - The International Affective Picture System (IAPS) is increasingly used in brain
      imaging studies to examine emotional processes. This task allows valence and
      arousal content to be systematically investigated; however, previous studies have
      generally failed to select images that vary in one dimension as well as hold
      constant the variability on the other dimension. In addition, no studies have
      investigated the temporal structure associated with the conscious, ongoing
      processing of emotional stimuli following systematic selection of IAPS images.
      The aim of the present study was therefore to use steady-state probe topography
      (SSPT) to examine the steady-state visually evoked potentials (SSVEPs) associated
      with the processing of pleasant and unpleasant images low in arousal content.
      Seventy-five IAPS images, categorized as unpleasant, neutral, or pleasant, were
      presented to 16 healthy subjects while brain activity was recorded from 64 scalp
      sites. Analysis subtracted the activity associated with the presentation of
      neutral images from the activity associated with the presentation of pleasant as
      well as unpleasant images. Results demonstrate that both pleasant and unpleasant
      valence is associated with transient, widespread, and bilateral frontal SSVEP
      latency reductions. Unpleasant images were also associated with a transient
      bilateral anterior frontal amplitude decrease. Latency reductions are interpreted
      as increases in neural information processing speed, while amplitude reductions
      are interpreted in the current paper as analogous to an event-related
      desynchronisation commonly associated with the alpha bandwidth. These key
      findings support previous literature in terms of there being substantial overlap
      in frontal neural circuitry when the brain processes pleasant and unpleasant
      valence relative to neutral valence.

PMID- 12498743
TI  - Selective activation of a parietofrontal circuit during implicitly imagined
      prehension.
AB  - It is generally held that motor imagery is the internal simulation of movements
      involving one's own body in the absence of overt execution. Consistent with this
      hypothesis, results from numerous functional neuroimaging studies indicate that
      motor imagery activates a large variety of motor-related brain regions. However,
      it is unclear precisely which of these areas are involved in motor imagery per se
      as opposed to other planning processes that do not involve movement simulation.
      In an attempt to resolve this issue, we employed event-related fMRI to separate
      activations related to hand preparation-a task component that does not demand
      imagining movements-from grip selection-a component previously shown to require
      the internal simulation of reaching movements. Our results show that in contrast
      to preparation of overt actions, preparation of either hand for covert movement
      simulation activates a large network of motor-related areas located primarily
      within the left cerebral and right cerebellar hemispheres. By contrast, imagined
      grip selection activates a distinct parietofrontal circuit that includes the
      bilateral dorsal premotor cortex, contralateral intraparietal sulcus, and right
      superior parietal lobule. Because these areas are highly consistent with the
      frontoparietal reach circuit identified in monkeys, we conclude that motor
      imagery involves action-specific motor representations computed in parietofrontal
      circuits.

PMID- 12498744
TI  - Visualization of auditory habituation by fMRI.
AB  - The aim of this study was to measure and quantify habituation phenomena within
      the auditory cortex of 18 healthy subjects by means of fMRI. Auditory stimulation
      was done by digitally generated pulsed (nu = 5 Hz) 800-Hz sine tones with three
      alternating ON (duration 2 min) and OFF (1 min) periods. Binaural stimulation
      resulted in symmetrical bihemispheric activation of the auditory cortex. Our data
      revealed a characteristic signal decay to repeated acoustic stimulation: the
      response to the second was even more pronounced, and the third stimulation block
      significantly lower compared to the first. Thus, our data clearly demonstrate
      habituation phenomena, probably due to reduced neuronal activity with increased
      duration and/or frequency of stimuli.

PMID- 12498746
TI  - Age-related differences in movement representation.
AB  - Repetitive movements have been used as motor activation tasks in the
      investigation of various neurological disorders. To determine the importance of
      an age-matched control group in such studies we investigated whether there are
      significant age-related changes in the pattern of cortical activation seen during
      simple repetitive movements. Sixteen right-handed healthy subjects were studied-8
      young and 8 old. Functional magnetic resonance images were acquired while
      subjects performed a motor task or a nonmovement rest condition. Two continuous
      motor tasks, index finger abduction/adduction and wrist extension/flexion, were
      performed by each hand, paced using a metronome. The fMRI data were processed and
      analyzed with SPM '99. For the between-group comparisons, for each motor task,
      contralateral primary sensorimotor cortex and premotor cortex had significantly
      greater activation in the Young group and caudal supplementary motor area had
      significantly greater activation in the Old group. Ipsilateral sensorimotor
      cortex was more significantly activated in the Old group for index finger motor
      tasks of both hands. All noted differences in the Old group were more prominent
      for the index finger movement and most prominent when using the nondominant hand.
      In conclusion, there are significant age-related differences in the activation
      pattern associated with repetitive movements. This may represent compensatory
      recruitment of motor cortical units in the older subjects as larger differences
      are noted in the older group during the more difficult motor tasks, those of
      isolated finger movement and nondominant hand use. This study has important
      implications for functional imaging experiments of neurological disorders in
      older subjects.

PMID- 12498745
TI  - Voxel-based morphometric analysis of gray matter in first episode schizophrenia.
AB  - Voxel-based morphometry (VBM) may afford a more rapid and extensive survey of
      gray matter abnormalities in schizophrenia than manually drawn region of interest
      (ROI) analysis, the current gold standard in structural MRI. Unfortunately, VBM
      has not been validated by comparison with ROI analyses, nor used in first-episode
      patients with schizophrenia or affective psychosis, who lack structural changes
      associated with chronicity. An SPM99-based implementation of VBM was used to
      compare a group of 16 patients with first-episode schizophrenia and a group of 18
      normal controls and, as a further comparison, 16 first-episode patients with
      affective psychosis. All groups were matched for age and handedness. High spatial
      resolution structural images were normalized to the SPM99 template and then
      segmented, smoothed, and subjected to an ANCOVA. Schizophrenia vs control group
      comparisons: Voxel-by-voxel comparison of gray matter densities showed that only
      the left STG region was significantly different when corrected for multiple
      comparisons (P <.05), consistent with our previously reported manual ROI results.
      Analysis of the extent of voxel clusters, replicated with permutation analyses,
      revealed group differences in bilateral anterior cingulate gyri and insula (not
      previously examined by us with manually drawn ROI) and unilateral parietal lobe,
      but not in medial temporal lobe (where our ROI analysis had shown differences).
      However, use of a smaller smoothing kernel and a small volume correction revealed
      left-sided hippocampal group differences. Affective psychosis comparisons: When
      the same statistical thresholding criteria were used, no significant differences
      between affective psychosis patients and controls were noted. Since a major
      interest was whether patients with affective psychosis shared some anatomical
      abnormalities with schizophrenia, we applied a small volume correction and
      searched within the regions that were significantly less dense in schizophrenia
      compared to control subjects. With this statistical correction, the insula
      showed, bilaterally, the same pattern of differences in affective disorder
      subjects as that in schizophrenic subjects, whereas both left STG and left
      hippocampus showed statistical differences between affectives and schizophrenics,
      indicating the abnormalities specific to first-episode schizophrenia. These
      findings suggest both the promise and utility of VBM in evaluating gray matter
      abnormalities. They further suggest the importance of comparing VBM findings with
      more traditional ROI analyses until the reasons for the differences between
      methods are determined.

PMID- 12498747
TI  - Visual imagery of famous faces: effects of memory and attention revealed by fMRI.
AB  - Complex pictorial information can be represented and retrieved from memory as
      mental visual images. Functional brain imaging studies have shown that visual
      perception and visual imagery share common neural substrates. The type of memory
      (short- or long-term) that mediates the generation of mental images, however, has
      not been addressed previously. The purpose of this study was to investigate the
      neural correlates underlying imagery generated from short- and long-term memory
      (STM and LTM). We used famous faces to localize the visual response during
      perception and to compare the responses during visual imagery generated from STM
      (subjects memorized specific pictures of celebrities before the imagery task) and
      imagery from LTM (subjects imagined famous faces without seeing specific pictures
      during the experimental session). We found that visual perception of famous faces
      activated the inferior occipital gyri, lateral fusiform gyri, the superior
      temporal sulcus, and the amygdala. Small subsets of these face-selective regions
      were activated during imagery. Additionally, visual imagery of famous faces
      activated a network of regions composed of bilateral calcarine, hippocampus,
      precuneus, intraparietal sulcus (IPS), and the inferior frontal gyrus (IFG). In
      all these regions, imagery generated from STM evoked more activation than imagery
      from LTM. Regardless of memory type, focusing attention on features of the
      imagined faces (e.g., eyes, lips, or nose) resulted in increased activation in
      the right IPS and right IFG. Our results suggest differential effects of memory
      and attention during the generation and maintenance of mental images of faces.

PMID- 12498748
TI  - Neural correlates of timbre change in harmonic sounds.
AB  - Timbre is a major structuring force in music and one of the most important and
      ecologically relevant features of auditory events. We used sound stimuli selected
      on the basis of previous psychophysiological studies to investigate the neural
      correlates of timbre perception. Our results indicate that both the left and
      right hemispheres are involved in timbre processing, challenging the conventional
      notion that the elementary attributes of musical perception are predominantly
      lateralized to the right hemisphere. Significant timbre-related brain activation
      was found in well-defined regions of posterior Heschl's gyrus and superior
      temporal sulcus, extending into the circular insular sulcus. Although the extent
      of activation was not significantly different between left and right hemispheres,
      temporal lobe activations were significantly posterior in the left, compared to
      the right, hemisphere, suggesting a functional asymmetry in their respective
      contributions to timbre processing. The implications of our findings for music
      processing in particular and auditory processing in general are discussed.

PMID- 12498749
TI  - Computational models of MRI characteristics of focal cortical dysplasia improve
      lesion detection.
AB  - In many patients, focal cortical dysplasia (FCD) is characterized by minor
      structural changes that may go unrecognized by standard radiological analysis. We
      previously demonstrated that visual analysis of a composite map based on three
      simple models of MRI features of FCD increased the sensitivity of FCD lesion
      detection, compared to visual analysis of conventional MRI. Here we report on the
      use of improved methods for characterizing FCD which improve contrast in the
      composite maps: a Laplacian-based metric for measuring cortical thickness, a
      convolutional kernel to model blurring of the GM-WM interface, and an operator to
      measure hyperintense T1 signal. To validate these methods, we processed the MRIs
      of 14 FCD patients with our original set of image processing operators and an
      improved set of image processing operators. Comparison of the composite maps
      associated with the two sets of operators revealed that contrast between lesional
      tissue and nonlesional cortex was significantly increased in the composite maps
      associated with the set of improved operators. Increasing this contrast is an
      important step toward the goal of automated FCD lesion detection.

PMID- 12498750
TI  - Modulation of the lexical-semantic network by auditory semantic priming: an event
      related functional MRI study.
AB  - The current event-related fMRI study specifies the neuroanatomical correlates of
      semantic priming and differences in semantic relation types using an auditory
      primed lexical decision task (LDT). Word pairs consisted of different relation
      types, associations (key-chain), pure categorical relations (cow-dog), and
      unrelated words (table-window), as well as word-pseudoword (way-tinne) and
      pseudoword-pseudoword (ahurn-dova) pairs. The factor lexical status, i.e., the
      processing of words compared to pseudowords, was associated with activation in
      the middle temporal gyri and the left striatum. The factor relatedness, i.e., the
      contrast between unrelated and related target words, was associated with
      increased activation of the left inferior frontal gyrus, the deep frontal
      operculum bilaterally, and the middle frontal gyri. A direct contrast between the
      two semantic relation types indicated that the processing of purely categorical
      compared to associative information recruits the right precuneus, the isthmus
      gyrus cinguli, and the cuneus, suggesting more effortful processing of the former
      information type. The present data show that the factors lexical status, semantic
      relatedness, and type of semantic relation in a primed LDT modulate the
      hemodynamic response in cerebral areas that subserve auditory word recognition
      and subsequent lexical-semantic processing.

PMID- 12498751
TI  - Independent components of magnetoencephalography: single-trial response onset
      times.
AB  - Werecently demonstrated that second-order blind identification (SOBI), an
      independent component analysis (ICA) method, can separate the mixture of neuronal
      and noise signals in magnetoencephalographic (MEG) data into neuroanatomically
      and neurophysiologically meaningful components. When the neuronal signals had
      relatively higher trial-to-trial variability, SOBI offered a particular advantage
      in identifying and localizing neuronal source activations with increased source
      detectability (A. C. Tang et al., 2002, Neural Comput. 14, 1827-1858). Here, we
      explore the utility of SOBI in the analysis of temporal aspects of neuromagnetic
      signals from MEG data. From SOBI components, we were able to measure single-trial
      response onset times of neuronal populations in visual, auditory, and
      somatosensory modalities during cognitive and sensory activation tasks, with a
      detection rate as high as 96% under optimal conditions. Comparing the SOBI-aided
      detection results with those obtained directly from the sensors, we found that
      with SOBI preprocessing, we were able to measure, among a greater proportion of
      trials, single-trial response onset times that are above background neuronal
      activity. We suggest that SOBI ICA can improve our current capability in
      measuring single-trial responses from human subjects using the noninvasive brain
      imaging method MEG.

PMID- 12498752
TI  - Neural basis of temporal context memory: a functional MRI study.
AB  - Temporal context information is crucial to understanding human episodic memory.
      Human lesion and neuroimaging data indicate that prefrontal regions are important
      for retrieving temporal context memory, although the exact nature of their
      involvement is still unclear. We employed functional magnetic resonance imaging
      (fMRI) to elucidate the neural basis of two kinds of temporal context memory: the
      temporal order of items between lists and within a list. On the day of the fMRI
      experiment, subjects memorized a list of 30 pictures in the morning and another
      list of 30 pictures in the afternoon. During the scanning session, the subjects
      performed three tasks. In a between-lists task, they were asked to judge the
      temporal order between two items that had been presented in different lists. In a
      within-list task, they were asked to judge the temporal order between two items
      that had been presented in a single list. We found bilateral prefrontal
      activities during these two temporal context memory tasks compared with a simple
      item-recognition task. Furthermore, in direct comparison between these two tasks,
      we found differential prefrontal activities. Thus, right prefrontal activity was
      associated with temporal order judgment of items between lists, whereas left
      prefrontal activity was related to temporal order judgment of items within a
      list. These results indicate that retrieval processes of two kinds of temporal
      context memory are supported by different, but overlapping, sets of cerebral
      regions. We speculate that this reflects different cognitive processes for
      retrieving temporal context memory between separate episodes and within a single
      episode.

PMID- 12498753
TI  - Task-independent functional brain activity correlation with skin conductance
      changes: an fMRI study.
AB  - Lesions of the ventromedial prefrontal cortex cause a loss of skin conductance
      response (SCR) to stimuli with affective content and an inability to integrate
      information with social consequences into decisions. Previous behavioral studies
      using a gambling task were able to differentiate patients with lesions in this
      region from normal subjects. In the present imaging study, this region, among
      others, was shown to be "spontaneously" activated during three different
      cognitive states: a gambling task, a working memory task, and resting state. SCR
      data were simultaneously collected during the scanning process. Six subjects were
      scanned at 1.5 T during all three states, and one subject was scanned at 3 T
      during the resting state only. SCR data were used as a reference function for
      correlation analysis with the fMRI time series during each of the three tasks.
      SCR changes were evident during the gambling and two-back tasks as well as during
      rest. SCR activity was not observed to be specifically related to reward-based
      decisions in the gambling task. Correlation of the fMRI time series directly with
      the SCR data revealed a consistent set of activated regions. The activity of
      these regions showing correlation with the SCR appeared independent of the
      cognitive state. Further, the subject scanned only at rest (without the possible
      confound of task-related carryover activity) replicated the findings in the
      original six subjects. From these data, SCR appears to be a marker of a network
      that is active during, but independent of, the task being studied.

PMID- 12498754
TI  - Mapping cortical gray matter asymmetry patterns in adolescents with heavy
      prenatal alcohol exposure.
AB  - Here we report on detailed three-dimensional quantitative maps of brain surface
      and gray matter density asymmetry patterns during normal adolescent development
      and show how these anatomical features of the brain are disrupted as a result of
      prenatal exposure to large quantities of alcohol. We studied two independent
      samples of normally developing children, adolescents, and young adults, totaling
      83 subjects from two different research groups, and compared them to 21
      individuals with heavy prenatal alcohol exposure. Surface-based image analysis
      techniques allowed us to match cortical anatomy across subjects and between
      hemispheres based on manually delineated sulcal landmarks. Quantitative maps of
      brain surface asymmetry reveal prominent peri-Sylvian hemispheric differences in
      which the superior temporal and inferior parietal cortices are shifted backward
      in the left relative to the right hemisphere in both normal and alcohol-exposed
      subjects. Cortical surface gray matter asymmetry, mapped here in adolescent
      populations, is most prominent in the posterior inferior temporal lobes (right
      greater than left), and this effect does not differ between groups of normally
      developing children, adolescents, or young adults. Alcohol-exposed individuals
      show a significant reduction in this asymmetry, whether studied with surface
      based or more traditional volumetric region of interest analyses. This region of
      cortex, near the junction of Brodmann's areas 21, 22, and 37, primarily subserves
      language functions that are known to be impaired on average in the alcohol
      exposed subjects. Our findings elucidate regional patterns of brain surface and
      gray matter asymmetry during normal development and may contribute to a more
      comprehensive understanding of the neural substrates of cognitive dysfunction
      after heavy prenatal alcohol exposure.

PMID- 12498755
TI  - Dissociable executive functions in the dynamic control of behavior: inhibition,
      error detection, and correction.
AB  - The present study employed event-related fMRI and EEG to investigate the
      biological basis of the cognitive control of behavior. Using a GO/NOGO task
      optimized to produce response inhibitions, frequent commission errors, and the
      opportunity for subsequent behavioral correction, we identified distinct cortical
      areas associated with each of these specific executive processes. Two cortical
      systems, one involving right prefrontal and parietal areas and the second regions
      of the cingulate, underlay inhibitory control. The involvement of these two
      systems was predicated upon the difficulty or urgency of the inhibition and each
      was employed to different extents by high- and low-absent-minded subjects. Errors
      were associated with medial activation incorporating the anterior cingulate and
      pre-SMA while behavioral alteration subsequent to errors was associated with both
      the anterior cingulate and the left prefrontal cortex. Furthermore, the EEG data
      demonstrated that successful response inhibition depended upon the timely
      activation of cortical areas as predicted by race models of response selection.
      The results highlight how higher cognitive functions responsible for behavioral
      control can result from the dynamic interplay of distinct cortical systems.

PMID- 12498756
TI  - Visual attention to words in different languages in bilinguals: a
      magnetoencephalographic study.
AB  - We recorded evoked magnetic fields from bilingual subjects while they were
      visually presented with words. The task was to count words in a target language
      when most of the words were in another language and there were also nontarget
      deviants in a third language. Our results indicate that in a multilingual visual
      environment there is a different need for attention to a nontarget language
      depending on whether the subject is attending to words in the subject's first
      (L1) or second (L2) language. When words in L2 are attended to, more effort
      appears to be devoted to words in the nontarget language than when words in L1
      are attended to. In addition, attention to the nontarget language while counting
      words in L2 does not seem to depend on the age of acquisition of L2.

PMID- 12498757
TI  - Contribution of corticospinal tract damage to cortical motor reorganization after
      a single clinical attack of multiple sclerosis.
AB  - The objectives of this study were to assess whether cortical motor reorganization
      in the early phase of multiple sclerosis (MS) is correlated with the clinical
      presentation and with specific damage to the corticospinal tract. Twenty patients
      with clinically isolated syndrome (CIS) and serial MR findings indicative of MS
      were selected. In 10 patients the CIS was hemiparesis (group H), and in 10
      patients the CIS was optic neuritis (group ON). There were no significant
      differences in age, disease duration, total T2 lesion load (LL), and total T1 LL
      between group H and group ON. Ten age-matched healthy subjects served as controls
      (group C). All subjects were submitted to fMRI during a sequential finger-to
      thumb opposition task of the right hand. Group H showed a significantly higher
      EDSS score and T1 LL calculated along the corticospinal tract than group ON.
      Three-group comparison by ANOVA showed significantly higher activation in group H
      than in the other two groups (P < 0.001). Significant foci were located in the
      sensory-motor cortex (BA 1-4), the parietal cortex (BA 40), the insula of the
      ipsilateral hemisphere, and the contralateral motor cortex (BA 4/6). Group ON
      showed, although at a lower level of significance (P < 0.01), higher activation
      of the contralateral motor-related areas than group C. Multiple regression
      analysis showed that T2 and T1 LL along the corticospinal tract and time since
      clinical onset positively correlated with activation in motor areas in both
      cerebral hemispheres (P < 0.005). Total T2 LL positively correlated with
      activation in motor areas in the contralateral hemisphere (P < 0.005). Total T1
      LL and EDSS did not show any significant correlation. More severe specific damage
      to the motor pathway in patients with previous hemiparesis may explain the
      significantly higher involvement of ipsilateral motor areas observed in group H
      than in group ON. Furthermore, the significant correlation between the time since
      clinical onset and activation in motor areas suggests that cortical
      reorganization develops gradually in concomitance with the subclinical
      accumulation of tissue damage.

PMID- 12498758
TI  - Interscan displacement-induced variance in PET activation data is excluded by a
      scan-specific attenuation correction.
AB  - In PET activation studies, linear changes in regional cerebral blood flow may be
      caused by subject interscan displacements rather than by changes in cognitive
      state. The aim of this study was to investigate the impact of these artifacts and
      to assess whether they can be removed by applying a scan-specific calculated
      attenuation correction (CAC) instead of the default measured attenuation
      correction (MAC). Two independent data sets were analyzed, one with large (data
      I) and one with small (data II) interscan displacements. After attenuation
      correction (CAC or MAC), data were analyzed using SPM99. Interscan displacement
      parameters (IDP), obtained during scan realignment, were included as additional
      regressors in the General Linear Model and their impact was assessed by variance
      statistics revealing the affected brain volume. For data I, this volume reduced
      dramatically from 579 to 12 cm(3) (approximately 50-fold) at P(uncorr) </= 0.001
      and from 100 to 0 cm(3) at P(corr) </= 0.05 when CAC was applied instead of MAC.
      Surprisingly, for data II, applying CAC instead of MAC still resulted in a
      substantial (approximately 10-fold) reduction of the affected volume from 23 to 2
      cm(3) at P(uncorr) </= 0.001. We conclude that interscan displacement-induced
      variance can be prevented by applying a (realigned attenuation correction scan
      (e.g., CAC). With MAC data, introducing IDP covariates is not an alternative
      since they model only this variance. Even in data with minor interscan
      displacements, applying a (realigned attenuation correction method (e.g., CAC) is
      superior to a nonaligned MAC with IDP covariates.

PMID- 12498759
TI  - Mapping of neuronal function in the healthy and injured human spinal cord with
      spinal fMRI.
AB  - Functional magnetic resonance imaging of the human spinal cord is carried out
      with a graded thermal stimulus in order to establish the relationship between
      signal changes and neural activity. Studies of the lumbar spinal cord in 15
      healthy subjects with 10 degrees C stimulation of the skin overlying the calf
      demonstrate a pattern of activity that matches the neuronal anatomy of the spinal
      cord. This pattern shows primarily dorsal horn activity, with expected components
      of motor reflex activity as well. Moreover, a later response shifting to noxious
      cold over time is also demonstrated with a shift to more dorsal horn activity.
      Signal intensity changes detected at different degrees of thermal stimulation
      have a biphasic nature, with much larger signal changes below 15 degrees C as the
      stimulus becomes noxious, and agree well with electrophysiological results
      reported in the literature. These findings demonstrate a strong correspondence
      between Spinal fMRI results and neural activity in the human spinal cord. Spinal
      fMRI is also applied to studies of the injured spinal cord, below the site of
      injury. Results consistently demonstrate activity in the spinal cord even when
      the subjects cannot feel the stimulus being applied. Signal intensity changes
      demonstrate the same stimulus-response pattern as that in noninjured subjects,
      but the areas of activity in the spinal gray matter are notably altered. In
      subjects with complete injuries, activity is absent ipsilateral to the thermal
      stimulation, but appears to be enhanced on the contralateral side. These findings
      demonstrate the reliability of Spinal fMRI and its clinical potential.

PMID- 12498760
TI  - A direct test for lateralization of language activation using fMRI: comparison
      with invasive assessments in children with epilepsy.
AB  - This study introduces a direct method of assessing cerebral lateralization for
      language based on fMRI activation. The method, derived from a voxel-based
      morphometry study by C. H. Salmond et al. (2000, Hum. Brain Mapping 11, 223-232),
      bases lateralization on the direct statistical comparison of the magnitude of
      task-induced activation in homotopic regions of the two hemispheres.
      Lateralization results obtained with this direct method were compared to those
      obtained with a widely used method which involves the calculation of a laterality
      index (LI) based on the number of significantly activated voxels in the inferior
      frontal gyrus of each hemisphere. In order to compare the validity of the two
      methods, a covert verb-generation task was performed by eight children with
      epilepsy whose language lateralization was examined using invasive techniques.
      Lateralization results derived from fMRI activation showed that the calculation
      of a LI presented some limitations. Importantly, the LI value was dependent on
      the activation threshold chosen to calculate that LI. As a consequence, the
      correlation between the LI and the invasive methods could vary with the chosen
      threshold. By contrast, the proposed direct method gave some indication of the
      reliability of the lateralization and provided results that, in all eight
      children, were consistent with those obtained using invasive techniques. It is
      suggested that the direct method could be used in future fMRI studies to
      establish hemispheric lateralization for cognitive functions.

PMID- 12498761
TI  - Functional frequency-domain near-infrared spectroscopy detects fast neuronal
      signal in the motor cortex.
AB  - Millisecond changes in the optical properties of the human brain during
      stimulation were detected in five volunteers using noninvasive frequency-domain
      near-infrared spectroscopy. During a motor stimulation task we found highly
      significant signals, which were directly related to neuronal activity and
      exhibited much more localized patterns than the slow hemodynamic signals that are
      also detected by the near-infrared method. We considerably reduced the noise in
      the instrumental system and improved data analysis algorithms. With the achieved
      signal-to-noise ratio, single subject measurements were feasible without the
      requirement of particularly strong stimuli and within a reasonable period of
      measurement of 5 min at a mean signal-to-noise ratio of 3.6. The advantage of
      this noninvasive technique with respect to electrical recording is that it is
      able to detect neuronal activity with the relatively high spatial resolution of 8
      mm.

PMID- 12498762
TI  - Cerebral blood flow change in arterial hypoxemia is consistent with negligible
      oxygen tension in brain mitochondria.
AB  - The regulation of blood flow during neuronal activation is poorly understood.
      Current explanations of the mismatch between increased blood flow and oxygen
      consumption during neuronal excitation hold that blood flow must rise more than
      oxygen consumption to compensate for a low oxygen reserve in brain mitochondria.
      Contrary to the result of a previous study by Mintun et al. (2001), the present
      test of the hypothesis revealed no conflicts among the claims of unidirectional
      blood-brain transfer of oxygen, negligible oxygen in mitochondria, and
      measurements of cerebral blood flow and oxygen consumption. With a simple
      compartmental model of oxygen delivery to brain tissue, the test showed that
      neuronal excitation elicits identical increases of cerebral blood flow in
      normoxemia and hypoxemia, in complete agreement with the claim of a negligible
      reserve of oxygen in brain mitochondria in vivo.

PMID- 12498763
TI  - Making the promise a reality.

PMID- 12498764
TI  - 2002 Nobel Prize for physiology and medicine.

PMID- 12498765
TI  - Sperm mediated transgenesis rushes 'back to the future'.

PMID- 12498766
TI  - Decreased insulitis and blood glucose levels after injection of GAD-transduced
      lymphocytes into NOD mice.
AB  - We used NOD mice to investigate the effects of injecting transduced lymphocytes
      on insulitis, nonfasting blood glucose levels, and immune responses. Syngeneic
      splenocytes were transduced with retroviral particles carrying a cDNA construct
      encoding the beta cell antigen glutamic acid decarboxylase (GAD65), a secreted
      form of GAD65 (SGAD55), or secreted alkaline phosphatase (SEAP) as a control
      antigen. Different multiplicities of infection (m.o.i.) were used with different
      constructs. Four-week-old NOD mice received intravenous injection of CD4(+) cells
      isolated from transduced splenocytes, and insulitis and blood glucose levels were
      determined at 10 weeks of age. No significant effects were observed with
      lymphocytes transduced with gad65 and sgad55 constructs at low m.o.i. By
      contrast, at high m.o.i., lymphocytes transduced with the sgad55 and seap
      constructs caused a decrease in insulitis and blood glucose levels and in
      insulitis alone, respectively. ELISA of anti-GAD antibody isotypes indicated that
      GAD-transduced lymphocytes induced similar Th2-like responses at all m.o.i. These
      results suggest that retroviral particles carrying sgad55 can be used for
      engineering cell vaccines for type 1 diabetes and provide further evidence that
      Th2-like responses induced by immunization may not always be a primary cause of
      diabetes suppression in NOD mice.

PMID- 12498767
TI  - Bone-marrow-derived macrophages genetically modified to produce IL-10 reduce
      injury in experimental glomerulonephritis.
AB  - Macrophages are intimately involved in the development of immune-mediated
      inflammation, including glomerulonephritis. We have transduced primary cultures
      of macrophages to express IL-10 and tested the ability of these cells to control
      rat nephrotoxic nephritis (NTN), a model of human glomerulonephritis. Ad-IL-10
      transduced bone-marrow-derived macrophages (BMDM) produced large amounts of IL-10
      in culture, and their TNF-alpha production was decreased in response to
      interferon-gamma and LPS. Transduced macrophages were injected into the renal
      artery of rats, 6 h after the induction of NTN, where they localized efficiently
      to inflamed rat glomeruli. Delivery of IL-10-expressing macrophages to nephritic
      rats produced a marked reduction in albuminuria compared with unmodified NTN or
      injection of Ad-null-transduced BMDM. IL-10 treatment decreased the number of
      glomerular ED1- and ED3-positive cells, MHC class II expression, and the number
      of fibrinoid lesions. Interestingly, anti-inflammatory changes in the Ad-IL-10
      injected kidney were mirrored by changes in the contralateral kidney. These
      results highlight that Ad-IL-10-transduced macrophages infiltrate inflamed
      glomeruli and reduce the severity of glomerular inflammation, emphasizing the
      value of local delivery of genetically modified macrophages in the manipulation
      of inflammatory disease.

PMID- 12498768
TI  - Repair of a splicing defect in erythroid cells from patients with beta
      thalassemia/HbE disorder.
AB  - A HeLa cell line stably expressing the human beta-globin gene carrying
      thalassemic mutations beta(E)/IVS1-6 served as a thalassemia model for repair of
      aberrant splicing of beta(E)-globin pre-mRNA with antisense oligonucleotides.
      Treatment of beta(E)/IVS1-6 HeLa cells with a morpholino oligonucleotide targeted
      immediately upstream of the aberrant 5' splice site activated by the mutations
      resulted in an increase in the amount of correctly spliced beta(E)-globin mRNA in
      a dose-dependent and sequence-specific fashion. The repaired beta(E)-globin mRNA
      was stable and could be translated into full-length beta(E)-globin polypeptide.
      Application of the same oligonucleotide to erythroid progenitor cells from two
      beta-thalassemia/HbE patients resulted in an approximately 70% increase in
      correct beta(E)-globin mRNA and 36% increase in hemoglobin E. The erythroid
      progenitor cells represent the actual targets for the clinical application of
      antisense repair of defective pre-mRNAs.

PMID- 12498769
TI  - Intraarticular gene transfer of TNFR:Fc suppresses experimental arthritis with
      reduced systemic distribution of the gene product.
AB  - Tumor necrosis factor alpha (TNFalpha) plays a pivotal role in the pathogenesis
      of rheumatoid arthritis (RA). Blockage of TNFalpha actions by systemic
      administration of TNF antagonists has recently been shown to ameliorate joint
      symptoms in RA patients. In the present study, a streptococcal cell wall (SCW)
      induced rat arthritis model was used to evaluate the effect of different gene
      transfer routes of a TNF antagonist on the development and severity of arthritis.
      Successful delivery of a plasmid DNA encoding a rat TNF receptor-immunoglobulin
      Fc (TNFR:Fc) fusion gene prompted the subsequent administration of a recombinant
      adeno-associated virus (rAAV) vector encoding the antagonist, either locally
      (intraarticular) or systemically (intramuscular). The TNFR:Fc gene, delivered by
      either route, resulted in profound suppression of the arthritis as reflected in
      decreased inflammatory cell infiltration, pannus formation, cartilage and bone
      destruction, and mRNA expression of joint proinflammatory cytokines. Increased
      bioactive serum TNFR levels were detected as a result of rAAV-ratTNFR:Fc
      administration, concomitant with a decrease in circulating TNFalpha.
      Administration of the rAAV-ratTNFR:Fc vector to one joint also suppressed
      arthritis in the contralateral joint. Importantly, intraarticular administration
      resulted in significantly lower systemic distribution of the gene product. Hence,
      the use of rAAV as the delivery vector for TNFR:Fc effectively suppressed SCW
      induced arthritis and may provide an approach for local delivery of antiarthritic
      therapy.

PMID- 12498770
TI  - Therapeutic effect of intravenous interferon gene delivery with naked plasmid DNA
      in murine metastasis models.
AB  - Interferons (IFNs) exhibit pleiotropic biological activities that are considered
      to play important roles in tumor suppression and rejection. Therefore, IFN genes
      are promising for in vivo cytokine gene therapy targeted against tumors. In the
      present study, we evaluated the efficacy of hydrodynamics-based IFN gene transfer
      for tumor treatment, in which the naked pDNA encoding IFN-beta or IFN-gamma was
      administered into the tail vein of mice following portal vein (liver metastasis),
      tail vein (lung metastasis), or subcutaneous injection (subcutaneous tumor) of
      mouse colon carcinoma CT-26 cells. A substantial amount of IFN was soon markedly
      expressed in the liver and a transient increase in IFN activity was detected in
      the circulation. This procedure caused transgene-specific IFN production with
      little induction of other proinflammatory cytokines. In the liver metastasis
      experiment, the mice treated with IFN-expressing pDNA displayed a profound
      reduction in liver metastasis and a prolonged survival. Administration of the
      pDNA at an earlier stage of metastasis was more crucial for the antitumor effect.
      Similar tumor suppression was seen in the lung metastasis experiment. These
      therapeutic effects were more marked with IFN-beta-expressing pDNA treatment than
      with IFN-gamma-expressing pDNA treatment. On the other hand, subcutaneous CT-26
      tumor growth was hardly affected by pDNA administration. These results suggest
      that the hydrodynamics-based transfer of naked pDNA is a convenient and efficient
      method of IFN gene therapy against metastatic tumors.

PMID- 12498771
TI  - Evaluation of pathological manifestations of disease in mucopolysaccharidosis VII
      mice after neonatal hepatic gene therapy.
AB  - Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease caused by beta
      glucuronidase (GUSB) deficiency. Intravenous injection of a retroviral vector
      expressing canine GUSB into neonatal MPS VII mice resulted in transduction of 6
      to 35% of hepatocytes, which secreted GUSB into blood. Serum GUSB activity was
      stable for 6 months at 600 (low expression) to 10,000 (high expression) U/ml, and
      enzyme was modified appropriately with mannose 6-phosphate. The average serum
      GUSB activity (3531 U/ml) is the highest long-term expression reported for MPS
      VII mice after gene therapy. Secreted enzyme was taken up by other tissues, as
      the average enzyme activity was >13% of normal in somatic organs and 2% of normal
      in brain. Low expression markedly reduced histopathological evidence of lysosomal
      storage in liver, spleen, kidney, small intestine, neurons, and glial cells. High
      expression appeared to be more effective than low expression at reducing
      lysosomal storage in aorta, heart valves, thymus, bronchial epithelium, cornea,
      and retinal pigmented epithelium. Future experiments will determine if greater
      pathological improvements will consistently be observed in retrovirus-treated MPS
      VII mice with higher serum GUSB activity relative to animals with lower activity
      and if these result in clinical benefits.

PMID- 12498772
TI  - In vivo correction of murine tyrosinemia type I by DNA-mediated transposition.
AB  - Gene therapy applications of naked DNA constructs for genetic disorders have been
      limited because of lack of permanent transgene expression. This limitation,
      however, can be overcome by the Sleeping Beauty (SB) transposable element, which
      can achieve permanent transgene expression through genomic integration from
      plasmid DNA. To date, only one example of an in vivo gene therapy application of
      this system has been reported. In this report, we have further defined the
      activity of the SB transposon in vivo by analyzing the expression and integration
      of a fumarylacetoacetate hydrolase (FAH) transposon in FAH-deficient mice. In
      this model, stably corrected FAH(+) hepatocytes are clonally selected and stable
      integration events can therefore be quantified and characterized at the molecular
      level. Herein, we demonstrate that SB-transposon-transfected hepatocytes can
      support significant repopulation of the liver, resulting in long-lasting
      correction of the FAH-deficiency phenotype. A single, combined injection of an
      FAH-expressing transposon plasmid and a transposase expression construct resulted
      in stable FAH expression in approximately 1% of transfected hepatocytes. The
      average transposon copy number was determined to be approximately 1/diploid
      genome and expression was not silenced during serial transplantation. Molecular
      analysis indicated that high-efficiency DNA-mediated transposition into the mouse
      genome was strictly dependent on the expression of wild-type transposase.

PMID- 12498773
TI  - RNA-based anti-HIV-1 gene therapeutic constructs in SCID-hu mouse model.
AB  - Effective suppression of HIV-1 replication requires inhibition of critical viral
      target molecules. Tat and Rev are indispensable regulatory factors for HIV-1
      replication, whereas Env mediates virus entry by direct interaction with surface
      receptor CD4 and coreceptor CCR5 or CXCR4. Anti-HIV-1 tat-rev and env ribozymes
      and Rev aptamers were previously demonstrated to provide relatively long-term
      protection against HIV-1 infection in vitro. However, further improvements in
      these constructs for clinical application in a stem-cell-based gene therapy
      setting requires in vivo characterization. Toward this end, we introduced these
      constructs into CD34(+) hematopoietic progenitor cells by retrovirus-mediated
      gene transduction. Ribozyme- and aptamer-transduced CD34(+) cells differentiated
      normally into multiple lineages of erythroid and myeloid progenies in a colony
      forming unit assay. Macrophages that differentiated from the transduced CD34(+)
      cells expressed anti-tat-rev and -env ribozymes and Rev aptamers and displayed
      their normal characteristic surface markers CD14, CD4, and CCR5. Using the SCID
      hu mouse in vivo human thymopoiesis model, we demonstrated that ribozyme- and
      aptamer-transduced CD34(+) cells retained their normal capacity to reconstitute
      human fetal thymus and liver tissue (thy/liv) grafts. Reconstitution by ribozyme-
      and aptamer-transduced CD34(+) cells reached levels of up to 87% based on HLA
      surface marker staining. Differentiated thymocytes derived from reconstituted
      grafts expressed anti-tat-rev and -env ribozymes and Rev aptamers and showed
      significant resistance to HIV-1 infection upon challenge. Analysis of
      reconstituted thymocytes by hybridization revealed an average of 0.4 to 2 copies
      of vector sequences per cell. Southern analysis of proviral integration junctions
      in progeny thymocytes demonstrated that the human thy/liv grafts were
      reconstituted by a few primitive hematopoietic stem cells. These results
      highlight the utility of RNA-based anti-HIV-1 gene therapeutic approaches and
      their preclinical testing in a surrogate animal model harboring human tissue.

PMID- 12498774
TI  - Enhanced gene expression in breast cancer cells in vitro and tumors in vivo.
AB  - Gene therapy clinical trials for cancer frequently produce inconsistent results.
      Some of this variability could result from differences in transcriptional
      regulation that limit expression of therapeutic genes in specific cancers.
      Systemic liposomal delivery of a nonviral plasmid DNA showed efficacy in animal
      models for several cancers. However, we observed large differences in the levels
      of gene expression from a CMV promoter-enhancer between lung and breast cancers.
      To optimize gene expression in breast cancer cells in vitro and in vivo, we
      created a new promoter-enhancer chimera to regulate gene expression. Serial
      analyses of gene expression data from a panel of breast carcinomas and normal
      breast cells predicted that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      promoter is highly active in breast cancers. Furthermore, GAPDH is up-regulated
      by hypoxia, which is common in tumors. We added the GAPDH promoter, including the
      hypoxia enhancer sequences, to our in vivo gene expression plasmid. The novel CMV
      GAPDH promoter-enhancer showed up to 70-fold increased gene expression in breast
      tumors compared to the optimized CMV promoter-enhancer alone. No significant
      increase in gene expression was observed in other tissues. These data demonstrate
      tissue-specific effects on gene expression after nonviral delivery and suggest
      that gene delivery systems may require plasmid modifications for the treatment of
      different tumor types. Furthermore, expression profiling can facilitate the
      design of optimal expression plasmids for use in specific cancers.

PMID- 12498775
TI  - Mechanisms leading to sustained reversion of beta-thalassemia in mice by
      doxycycline-controlled Epo delivery from muscles.
AB  - Erythropoiesis has been considered as a potential treatment for beta-thalassemia.
      Although Epo secretion from genetically engineered muscles allowed long-term
      correction of the disease in the mouse, repeated injections of rHuEpo were
      disappointing in human patients. Whether different mechanisms operate in humans
      and mice or whether Epo exhibits different biological activity depending on the
      administration route is currently unknown. We provide evidence that mechanisms
      recruited over a 36-week follow-up in beta-thalassemic mice were similar to those
      acting during stress-induced erythropoiesis in humans. beta-Thalassemic mice were
      rendered steadily normocythemic by the intramuscular injection of a tetracycline
      inducible AAV vector encoding mouse Epo. Doxycycline dosage was adapted to
      hematocrit. Circulating red blood cells essentially synthesized beta-minor
      globin, the mouse equivalent to human gamma-globin. Quantification of erythroid
      progenitors indicated a steady-state expansion of erythroid burst-forming units
      programmed for beta-minor globin synthesis and a hastening of their maturation to
      hemoglobin-synthesizing cells. We discuss hypotheses that could account for the
      failure to recruit this mechanism over the long term in beta-thalassemic patients
      and raise the possibility of Epo gene therapy trials to treat beta-thalassemia.

PMID- 12498776
TI  - Codelivery of NF-kappaB decoy-related oligodeoxynucleotide improves LPD-mediated
      systemic gene transfer.
AB  - A systemic gene delivery vector for LPD (cationic liposome-polycation-DNA) has
      been reported previously to transfect the pulmonary endothelium and holds promise
      for treating pulmonary diseases. However, the uptake of LPD by immune cells
      triggers a strong inflammatory response that is toxic to animals and limits
      transgene expression. In this study, LPD was used to codeliver phosphorothioate
      oligodeoxynucleotides (ODNs) containing an NF-kappaB consensus binding sequence
      with plasmid DNA carrying a reporter gene. Codelivery of a single-stranded kappaB
      ODN inhibited TNF-alpha induction by LPD-plasmid delivery and increased transgene
      expression in the lung in a dose-dependent manner. A similar effect was observed
      with the double-stranded ODN of the same sequence at twice the dose, and the
      complementary ODN (antisense) had no effect. Sequence mutation study suggested
      that the effect was sequence specific and these ODNs may achieve their effect
      through interaction with NF-kappaB family proteins in a decoy manner. In addition
      to enhancing gene transfer, these single-stranded ODNs formulated in LPD may be
      explored as anti-inflammatory agents.

PMID- 12498777
TI  - Intercellular trafficking of adenovirus-delivered HSV VP22 from the retinal
      pigment epithelium to the photoreceptors--implications for gene therapy.
AB  - Adenovirus (Ad)-mediated gene transfer is a promising technology for therapy of a
      wide variety of genetic disorders of the retina. The tropism of Ad vectors limits
      their utility to cells that express the coxsackie-adenovirus receptor. Upon
      ocular delivery, Ad vectors primarily infect the retinal pigment epithelium (RPE)
      and the Muller cells of the retina. However, the most frequent blinding diseases
      such as retinitis pigmentosa and age-related macular degeneration are associated
      with the expression of mutant proteins in the photoreceptors. In this study we
      demonstrate that adenovirus-delivered heterologous proteins fused to the herpes
      simplex virus tegument protein VP22 can translocate from infected cells to
      uninfected cells in culture and in vivo. We tested three different ocular cell
      lines, specifically Y79, RPE-J, and Chang C. We show that there is a 3.25-fold
      increase in the number of Y79 cells that take up GFP mediated by the
      intercellular trafficking properties of VP22. Our data are based on FACS analysis
      of living cells and there was no need for cell fixation for the effect to be
      observed. When adenovirus expressing a VP22-GFP fusion was injected into the
      subretinal space of adult mice, the VP22-GFP fusion peptides translocated from
      the RPE to all of the other layers of the retina, including the outer nuclear
      layer, which contains the photoreceptor cell bodies. Our study has significant
      implications for a wide variety of diseases of the retina and other organ
      systems.

PMID- 12498778
TI  - Direct genetic correction as a new method for diagnosis and molecular
      characterization of MHC class II deficiency.
AB  - Major histocompatibility complex class II (MHCII) deficiency is a primary
      immunodeficiency resulting from defects in one of four different MHCII-specific
      transcription factors-CIITA, RFX5, RFXAP, and RFXANK. Despite this genetic
      heterogeneity, the phenotypical manifestations are homogeneous. It is frequently
      difficult to establish a definitive diagnosis of the disease on the basis of
      clinical and immunological criteria. Moreover, the phenotypical homogeneity
      precludes unambiguous identification of the regulatory gene that is affected.
      Identification of the four genes mutated in the disease has now allowed us to
      develop a rapid and straightforward diagnostic test for new MHCII-deficiency
      patients. This test is based on direct correction of the genetic defect by
      transduction of cells from patients with lentiviral vectors encoding CIITA,
      RFXANK, RFX5, or RFXAP. We have validated this approach by defining the molecular
      defects in two new patients. The RFXANK vector restored MHCII expression in a T
      cell line from one patient. The RFXAP vector corrected primary cells (PBL) from a
      second patient. Molecular analysis confirmed the presence of homozygous mutations
      in the RFXANK and RFXAP genes, respectively. Direct genetic correction represents
      a valuable tool for the diagnosis and classification of new MHCII-deficiency
      patients.

PMID- 12498779
TI  - Effects of plasmid-mediated growth hormone-releasing hormone in severely
      debilitated dogs with cancer.
AB  - Cachexia is a common manifestation of late stage malignancy and is characterized
      by anemia, anorexia, muscle wasting, loss of adipose tissue, and fatigue.
      Although cachexia is disabling and can diminish the life expectancy of cancer
      patients, there are still no effective therapies for this condition. We have
      examined the feasibility of using a myogenic plasmid to express growth hormone
      releasing hormone (GHRH) in severely debilitated companion dogs with naturally
      occurring tumors. At a median of 16 days after intramuscular delivery of the
      plasmid, serum concentrations of insulin-like growth factor I (IGF-I), a measure
      of GHRH activity, were increased in 12 of 16 dogs (P < 0.01). These increases
      ranged from 21 to 120% (median, 49%) of the pretreatment values and were
      generally sustained or higher on the final evaluation. Anemia resolved
      posttreatment, as indicated by significant increases in mean red blood cell
      count, hematocrit, and hemoglobin concentrations, and there was also a
      significant rise in the percentage of circulating lymphocytes. Treated dogs
      maintained their weights over the 56-day study and did not show any adverse
      effects from the GHRH gene transfer. We conclude that intramuscular injection of
      a GHRH-expressing plasmid is both safe and capable of stimulating the release of
      growth hormone and IGF-I in large animals. The observed anabolic responses to a
      single dose of this therapy might be beneficial in patients with cancer
      associated anemia and cachexia.

PMID- 12498780
TI  - Bone morphogenetic proteins but not growth differentiation factors induce
      dopaminergic differentiation in mesencephalic precursors.
AB  - Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) are
      potential therapeutic molecules for the treatment of Parkinson's disease (PO).
      Here we compare the effects of BMP3, 5, 6, and 7 and GDF5 and 6 in a rat
      mesencephalic cell culture system that reflects the developmental stage of
      neurons around birth. High concentrations of BMP5, 6, and 7 and GDF5 and 6
      induced astroglial cell fate and a depletion of oligodendrocytes. Only BMP5, 6,
      and 7, however, significantly increased the number of tyrosine hydroxylase (TH)
      positive neurons and induced nuclear translocation of the phosphorylated BMP
      restricted Smad in a substantial number of TH- and microtubule-associated protein
      2(MAP2ab)-positive cells. None of the proteins protected TH-positive cells
      against 6-hydroxydopamine-induced oxidative stress. BMP3 was without any effect
      throughout the studies. We conclude that BMP5, 6, and 7 act directly and
      independently on precursors of the dopaminergic and astroglial lineage and induce
      their differentiation. In contrast, GDF5 and 6 primarily affect nonneuronal cells
      in mesencephalic cultures of this stage.

PMID- 12498781
TI  - Induction of STAT3 signaling in activated astrocytes and sprouting septal neurons
      following entorhinal cortex lesion in adult rats.
AB  - Entorhinal cortex lesion (ECL) leads to the activation of astrocytes and reactive
      axonal sprouting in the denervated fascia dentata. Previous studies indicated
      that CNTF or related cytokines are involved in the regulation of these processes.
      Therefore, we studied (1). whether the cytokine-associated STAT3 signaling
      pathway is activated in response to ECL and (2). which CNTF/cytokine receptor
      components are available for signal transduction. Lesion-induced STAT3
      phosphorylation was found in reactive astrocytes of the fascia dentata.
      Intriguingly, rapid and transient activation of STAT3 signaling was also observed
      in sprouting neurons of the medial septum. Messenger RNAs for the three
      components of the CNTF/cytokine receptor complex were expressed and
      differentially regulated following ECL both in septal neurons and in reactive
      astrocytes of the fascia dentata. These data indicate that CNTF or related gp130
      associated cytokines play a dual role after brain lesion: (1). regulation of
      astrocytic responses to deafferentation and (2). regulation or modulation of
      axonal sprouting.

PMID- 12498782
TI  - The calsyntenins--a family of postsynaptic membrane proteins with distinct
      neuronal expression patterns.
AB  - We have identified two novel postsynaptic membrane proteins that are highly
      similar to calsyntenin-1 in their extracellular parts but vary considerably in
      their cytoplasmic segment. Calsyntenin-1 has recently been identified in our lab
      as a postsynaptic membrane protein with a highly acidic cytoplasmic segment with
      putative Ca(2+)-binding capacity (Vogt et al., 2001, Mol. Cell. Neurosci. 17: 151
      166). Based on their structural similarity to calsyntenin-1, we have called the
      novel proteins calsyntenin-2 and -3, respectively. By immunoelectron microscopy,
      the calsyntenin protein family was localized in the postsynaptic membrane of
      excitatory central nervous system (CNS) synapses. In situ hybridization analysis
      revealed that calsyntenin-1 was abundant in most neurons of the CNS with
      relatively little variation in its expression level. Calsyntenin-2 and -3
      expressions varied much more with highest levels in GABAergic neurons. Based on
      their distinct expression patterns and the differences in their cytoplasmic
      segments, we suggest a cell-type-specific functional role for the three
      calsyntenins in excitatory synaptic transmission.

PMID- 12498783
TI  - CNS expression pattern of Lmx1b and coexpression with ptx genes suggest
      functional cooperativity in the development of forebrain motor control systems.
AB  - In the central nervous system, acquisition of regional specification is an
      important developmental process. The regional specification is reflected by
      restricted and overlapping expression of homeobox genes, which are regulators of
      this event. Here, we detail the expression pattern of Lmx1b during late embryonic
      brain development and show that this gene is expressed in multiple regions and
      diverse sets of neurons. Noteworthy, the Lmx1b expression domain is shared by
      Ptx2 in posterior hypothalamic regions and by Ptx3 in the dopaminergic neurons of
      the ventral midbrain. In addition, the mutual cofactor Ldb1 is expressed in these
      regions. The expression of these gene sets is maintained in the adult brain. The
      subthalamic nucleus, where Lmx1b is coexpressed with Ptx2, and the substantia
      nigra/ventral tegmental area, where Lmx1b is coexpressed with Ptx3, are both
      ancillary nuclei of the motor control circuitry, but use different
      neurotransmitters. These data point to a combinatorial gene network that allows
      Lmx1b to diversify its regulatory actions by cooperation with specific Ptx genes.

PMID- 12498784
TI  - Dynamic changes in gene expression profiles following axotomy of projection
      fibres in the Mammalian CNS.
AB  - Following postcommissural fornix transection we have investigated the postaxotomy
      transcriptional program in the subiculum where the injured axons originate. cDNA
      array hybridization revealed 125 genes that were specifically regulated as the
      injured neurons passed through three distinct postlesion (PL) stages comprising
      (i). early phase of injury and axon degeneration, (ii). sprouting phase of the
      proximal stump, and (iii). axonal growth arrest at the lesion scar. Numerous
      genes were detected which have, so far, not been associated with axotomy or
      axonal growth. Following the early lesion response that is characterized
      predominantly by down-regulation of genes at 1 day PL, neurons switch to a
      sprouting program with the majority of genes up-regulated at 7 days PL. However,
      the latter program of gene expression is not maintained but largely reversed (at
      3 weeks PL) to the initial profile as axonal growth is blocked at the lesion
      barrier, indicating retrograde signaling that leads to down-regulation of
      neuronal genes previously up-regulated during axon sprouting.

PMID- 12498785
TI  - Macrophages and Microglia Produce Local Trophic Gradients That Stimulate Axonal
      Sprouting Toward but Not beyond the Wound Edge.
AB  - Following injury to the mammalian CNS, axons sprout in the vicinity of the wound
      margin. Growth then ceases and axons fail to cross the lesion site. In this
      study, using dopaminergic sprouting in the injured striatum as a model system, we
      have examined the relationship of periwound sprouting fibers to reactive glia and
      macrophages. In the first week after injury we find that sprouting fibers form
      intimate relationships with activated microglia as they traverse toward the wound
      edge. Once at the wound edge, complicated plexuses of fibers form around
      individual macrophages. Axons, however, fail to grow further into the interior of
      the wound despite the presence of many macrophages in this location. We find that
      the expression of BDNF by activated microglia progressively increases as the
      wound edge is approached, while GDNF expression by macrophages is highest at the
      immediate wound margin. In contrast, the expression of both factors is
      substantially reduced within the macrophage-filled interior of the wound. Our
      data suggest that periwound sprouting fibers grow toward the wound margin along
      an increasing trophic gradient generated by progressively microglial and
      macrophage activation. Once at the wound edge, sprouting ceases over macrophages
      at the point of maximal neurotrophic factor expression and further axonal growth
      into the relatively poor trophic environment of the wound core fails to occur.

PMID- 12498786
TI  - Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin.
AB  - Synaptophysin is one of the most abundant proteins of the synaptic vesicle
      membrane. Here, we selected the cytoplasmic carboxyterminal region of
      synaptophysin to search for interacting proteins by using the yeast two-hybrid
      system. This identified gamma-adaptin, a component of the AP-1 adaptor complex,
      as a synaptophysin binding protein. An anti-synaptophysin antibody
      coimmunoprecipitated gamma-adaptin from brain extracts, and immunocytochemistry
      disclosed a partial colocalization of synaptophysin and gamma-adaptin in the
      perinuclear region of cultured hippocampal neurons. Our results are consistent
      with synaptophysin serving as a docking site for AP-1 during clathrin-dependent
      vesicle budding and/or kinesin-based transport reactions.

PMID- 12498787
TI  - Phosphorylation of hippocampal Erk-1/2, Elk-1, and p90-Rsk-1 during contextual
      fear conditioning: interactions between Erk-1/2 and Elk-1.
AB  - The phosphorylation of proteins involved in the MAP kinase signal transduction
      pathway was investigated during associative learning of C57BL/6J mice. Context
      dependent fear conditioning, consisting of a single exposure of mice to a context
      followed by foot shock, was employed as a learning paradigm. Control groups
      consisted of mice exposed to context only or an immediate shock in the context.
      Coincident up-regulation of phosphorylated Erk-1/2 and Elk-1 was observed in the
      CA3 hippocampal subfield and dentate gyrus 30 min after fear conditioning but not
      after the control paradigms. Phosphorylated Erk-1/2 and Elk-1 were associated and
      predominantly colocalized in the mossy fibers. In vitro kinase assays showed that
      hippocampal Erk-1/2 phosphorylates Elk-1. Notably, Elk-1 in turn enhances the
      phosphorylation of Erk-1/2 and its downstream target p90Rsk-1. Increased
      phosphorylation and nuclear translocation of p90Rsk-1 was also demonstrated in
      the CA3 hippocampal area in vivo during contextual fear conditioning. The
      observed interactions between hippocampal Elk-1 and Erk-1/2 proteins may affect
      the consolidation of contextual memories through activation of the downstream
      nuclear targets of Erk-1/2, such as p90Rsk-1, without requiring nuclear
      translocation of Elk-1 and Erk-1/2.

PMID- 12498788
TI  - NMDA receptor-dependent pattern transfer from afferents to postsynaptic cells and
      dendritic differentiation in the barrel cortex.
AB  - N-Methyl-D-aspartate receptors (NMDARs) are important for synaptic refinement
      during development. In CxNR1KO mice, cortical excitatory neurons lack NR1, the
      essential subunit of the NMDAR, and in their primary somatosensory (S1) cortex
      whisker-specific cellular patterns, "barrels," are absent. Despite this
      cytoarchitectural defect, thalamocortical axons (TCAs) representing the mystacial
      vibrissae form topographically organized patterns and undergo critical period
      plasticity. This region-specific knockout mouse model allows for dissection of
      the mechanisms underlying patterning of the pre- and postsynaptic neural elements
      in the S1 cortex. In the absence of functional NMDARs, layer IV cell numbers are
      unaltered, but these cells fail to segregate into barrels. Furthermore, the
      dendritic fields of spiny stellate cells do not orient toward TCA terminal
      patches as in normal mice. Instead, they radiate in all directions covering
      larger territories, exhibiting profuse branching with increased spine density.
      Comparison of TCA patches with serotonin transporter (5-HTT) immunohistochemistry
      or Dil labeling also indicates that in the CxNR1KO cortex TCAs form smaller
      patches and individual axon terminal branching is not as well developed as in
      control cortex. Our results suggest that postsynaptic NMDAR activation is
      critical in communicating periphery-related sensory patterns from TCAs to barrel
      cells. When postsynaptic NMDAR function is disrupted, layer IV spiny stellate
      cells remain imperceptive to patterning of their presynaptic inputs and elaborate
      exuberant dendritic specializations.

PMID- 12498789
TI  - Lithium ameliorates HIV-gp120-mediated neurotoxicity.
AB  - To investigate the protective effects of lithium against HIV-gp120-mediated
      toxicity in vivo, mice were exposed to lithium and gp120 and levels of the
      neuronal markers, microtubule-associated protein-2 and NeuN, and the astrocyte
      marker, glial fibrillary acidic protein, were determined. In addition, SH-SY5Y
      neuronal cells exposed to gp120 and lithium were assessed for cell viability.
      Lithium pretreatment protected the hippocampus of mice from gp120-mediated
      toxicity. Similarly, preexposure of neuronal cultures to lithium significantly
      reduced gp120-associated neurotoxicity. However, posttreatment with lithium had
      minimal neuroprotective effects against gp120, both in vivo and in vitro. The
      protective effects of lithium in vitro were blocked by LY294002, an inhibitor of
      the phosphatidylinositol 3-kinase/Akt pathway. Taken together, these results
      demonstrate that lithium might be neuroprotective against gp120-mediated toxicity
      and suggest that prophylactic treatment with lithium may prevent the
      onset/progression of HIV-associated cognitive impairments.

PMID- 12498790
TI  - Early steps in the production of sensory neurons by the neurogenic placodes.
AB  - Neurogenic placodes are specialized regions of the embryonic ectoderm that
      generate the majority of the neurons of the cranial sensory ganglia. Here we have
      accurately determined the onset of neurogenesis in each of the placodes in the
      chick, and we have also analyzed the expression profiles of genes that are
      believed to be involved in determining the types of sensory neurons produced by
      each placode. Interestingly, we find that there is a major difference in the
      expression domains of neurogenin-1 and neurogenin-2 in the chick, when compared
      with those reported for the mouse. We do find, however, that Brn-3a and Phox-2a
      and Phox-2b which are also associated with the specification of neuronal type are
      expressed in the same domains in the chick as they are in the mouse. These
      results suggest that neurogenin-1 and neurogenin-2 are functionally
      interchangeable in neurogenic placodes. We have also found major differences
      between the ophthalmic and maxillomandibular trigeminal placodes, and while all
      of the other placodes generate mitotically active cells the ophthalmic trigeminal
      placode seems to throw off postmitotic neuronal cells.

PMID- 12498791
TI  - Estrogen-receptor-dependent regulation of neural stem cell proliferation and
      differentiation.
AB  - Estrogen has profound effects on function and plasticity of the nervous system.
      Receptors for estrogen (ERs) are expressed by neurons in several areas of the
      brain. Here we demonstrate that embryonic and adult rat neural stem cells (NSC)
      express ERalpha and ERbeta, 17beta-Estradiol treatment decreased the
      proliferation of NSC stimulated by epidermal growth factor (EGF), which was due
      to the upregulation of the cyclin-dependent kinase (CDK) inhibitor, p21(Cip1).
      The modulatory effect of 17beta-estradiol on EGF was more pronounced in adult
      NSC. However, 17beta-estradiol alone increased the proliferation of embryonic,
      but not adult, NSC. The effect of 17beta-estradiol was inhibited by the ER
      antagonist, ICI-182780, showing an involvement of ERs. 17beta-Estradiol also
      increased the ratio of neurons to glia cells in embryonic NSC, but not in adult
      NSC, suggesting an influence on neurogenesis during embryonic development. The
      data show that estrogen, via ER, affects the proliferation and differentiation of
      NSC cells, probably acting in conjunction with other factors governing NSC
      development.

PMID- 12498792
TI  - Structures of phosphate and trivanadate complexes of Bacillus stearothermophilus
      phosphatase PhoE: structural and functional analysis in the cofactor-dependent
      phosphoglycerate mutase superfamily.
AB  - Bacillus stearothermophilus phosphatase PhoE is a member of the cofactor
      dependent phosphoglycerate mutase superfamily possessing broad specificity
      phosphatase activity. Its previous structural determination in complex with
      glycerol revealed probable bases for its efficient hydrolysis of both large,
      hydrophobic, and smaller, hydrophilic substrates. Here we report two further
      structures of PhoE complexes, to higher resolution of diffraction, which yield a
      better and thorough understanding of its catalytic mechanism. The environment of
      the phosphate ion in the catalytic site of the first complex strongly suggests an
      acid-base catalytic function for Glu83. It also reveals how the C-terminal tail
      ordering is linked to enzyme activation on phosphate binding by a different
      mechanism to that seen in Escherichia coli phosphoglycerate mutase. The second
      complex structure with an unusual doubly covalently bound trivanadate shows how
      covalent modification of the phosphorylable His10 is accompanied by small
      structural changes, presumably to catalytic advantage. When compared with
      structures of related proteins in the cofactor-dependent phosphoglycerate mutase
      superfamily, an additional phosphate ligand, Gln22, is observed in PhoE.
      Functional constraints lead to the corresponding residue being conserved as Gly
      in fructose-2,6-bisphosphatases and Thr/Ser/Cys in phosphoglycerate mutases. A
      number of sequence annotation errors in databases are highlighted by this
      analysis. B. stearothermophilus PhoE is evolutionarily related to a group of
      enzymes primarily present in Gram-positive bacilli. Even within this group
      substrate specificity is clearly variable highlighting the difficulties of
      computational functional annotation in the cofactor-dependent phosphoglycerate
      mutase superfamily.

PMID- 12498793
TI  - Bistable secondary structures of small RNAs and their structural probing by
      comparative imino proton NMR spectroscopy.
AB  - We investigate 25-34 nucleotide RNA sequences, that have been rationally designed
      to adopt two different secondary structures that are in thermodynamic
      equilibrium. Experimental evidence for the co-existence of the two conformers
      results from the NH...N 1H NMR spectra. When compared to the NH...N 1H NMR
      spectra of appropriate reference sequences the equilibrium position is easily
      quantifiable even without the assignment of the individual NH resonances. The
      reference sequences represent several Watson-Crick base-paired double helical
      segments, each encountered in either of the two conformers of the bistable target
      sequence. In addition, we rationalize the influence of nucleotide mutations on
      the equilibrium position of one of the bistable RNA sequences. The approach
      further allows a detailed thermodynamic analysis and the evaluation of secondary
      structure predictions for multistable RNAs obtained by computational methods.

PMID- 12498794
TI  - Solution structure of a DNA duplex containing 8-hydroxy-2'-deoxyguanosine
      opposite deoxyguanosine.
AB  - Deoxyguanosine residues are hydroxylated by reactive oxygen species at the C-8
      position to form 8-hydroxy-2'-deoxyguanosine (8-OG), one of the most important
      mutagenic lesions in DNA. Though the spontaneous G:C to C:G transversions are
      rare events, the pathways leading to this mutation are not established. An 8-OG:G
      mispair, if not corrected by DNA repair enzymes, could lead to G:C to C:G
      transversions. NMR spectroscopy and restrained molecular dynamics calculations
      are used to refine the solution structure of the base mismatch formed by the 8
      OG:G pair on a self complementary DNA dodecamer duplex d(CGCGAATT(8-O)GGCG)(2).
      The results reveal that the 8-OG base is inserted into the helix and forms
      Hoogsteen base-pairing with the G on the opposite strand. The 8-OG:G base-pairs
      are seen to be stabilized by two hydrogen bonding interactions, one between the
      H7 of the 8-OG and the O6 of the G, and a three-center hydrogen bonding between
      the O8 of the 8-OG and the imino and amino protons of the G. The 8-OG:G base
      pairs are very well stacked between the Watson-Crick base-paired flanking bases.
      Both strands of the DNA duplex adopt right-handed conformations. All of the
      unmodified bases, including the G at the lesion site, adopt anti glycosidic
      torsion angles and form Watson-Crick base-pairs. At the lesion site, the 8-OG
      residues adopt syn conformations. The structural studies demonstrate that 8
      OG(syn):G(anti) forms a stable pair in the interior of the duplex, providing a
      basis for the in vivo incorporation of G opposite 8-OG. Calculated helical
      parameters and backbone torsional angles, and the observed 31P chemical shifts,
      indicate that the structure of the duplex is perturbed near lesion sites, with
      the local unwinding of the double helix. The melting temperature of the 8-OG:G
      containing duplex is only 2.6 deg. C less than the t(m) of the unmodified duplex.

PMID- 12498795
TI  - Substitutions at Phe61 in the beta3-beta4 hairpin of HIV-1 reverse transcriptase
      reveal a role for the Fingers subdomain in strand displacement DNA synthesis.
AB  - Unlike most DNA polymerases, retroviral reverse transcriptases (RTs) are capable
      of strand displacement DNA synthesis in vitro, unassisted by other proteins.
      While human immunodeficiency virus type 1 (HIV-1) RT has been shown to possess
      this rare ability, the structural determinants responsible are unknown. X-Ray
      crystallographic and biochemical studies have indicated that the beta3-beta4
      hairpin of the fingers subdomain of HIV-1 RT contains key contacts for the
      incoming template strand. In order to assess the possible role of the fingers
      subdomain in strand displacement synthesis, a set of substitutions was created at
      the highly conserved Phe61 residue, which is thought to contact the template
      strand immediately ahead of the dNTP-binding site. Purified heterodimeric RTs
      containing Phe61 substitutions displayed altered degrees of strand displacement
      synthesis on nicked and gapped duplex DNA templates with the relative order
      being: F61Y > or = F61L > wild-type = F61A > F61W. In order to verify that the
      effects on strand displacement synthesis were not an indirect effect of
      alterations in processivity, all Phe61 mutants were tested for processive
      polymerization. While the strand displacement activity of F61W RT variant was
      affected severely, it displayed a wild-type-like processivity. In contrast, both
      F61L and F61Y substitutions, despite showing enhanced strand displacement
      synthesis, displayed reduced processivity. In contrast, the processivity of F61A
      mutant, which had displayed nearly wild-type-like strand displacement synthesis,
      was affected most. These results showed that the effects of Phe61 substitutions
      on strand displacement are not due to global changes in polymerase processivity.
      Analysis of pause sites during DNA polymerization on double-stranded templates
      revealed that the wild-type and the Phe61 mutant RTs interact with the template
      quite differently. Modeling a 5 nt duplex DNA ahead of the dNTP-binding site of
      HIV-1 RT suggested a correlation between the ability of the side-chain of the
      amino acid residue at position 61 to stabilize the first base-pair of the DNA
      duplex to be melted and the degree of strand displacement synthesis. Our results
      confirm a role for F61 residue in processive synthesis and indicate that the
      fingers subdomain harbors a structural determinant of strand displacement
      synthesis by HIV-1 RT.

PMID- 12498796
TI  - Structure of the filamentous phage pIV multimer by cryo-electron microscopy.
AB  - The homo-multimeric pIV protein constitutes a channel required for the assembly
      and export of filamentous phage across the outer membrane of Escherichia coli. We
      present a 22 A-resolution three-dimensional reconstruction of detergent
      solubilized pIV by cryo-electron microscopy associated with image analysis. The
      structure reveals a barrel-like complex, 13.5 nm in diameter and 24 nm in length,
      with D14 point-group symmetry, consisting of a dimer of unit multimers. Side
      views of each unit multimer exhibit three cylindrical domains named the N-ring,
      the M-ring and the C-ring. Gold labeling of pIV engineered to contain a single
      cysteine residue near the N or C terminus unambiguously identified the N-terminal
      region as the N-ring, and the C-terminal region was inferred to make up the C
      ring. A large pore, ranging in inner diameter from 6.0 nm to 8.8 nm, runs through
      the middle of the multimer, but a central domain, the pore gate, blocks it.
      Moreover, the pore diameter at the N-ring is smaller than the phage particle. We
      therefore propose that the pIV multimer undergoes a large conformational change
      during phage transport, with reorganization of the central domain to open the
      pore, and widening at the N-ring in order to accommodate the 6.5 nm diameter
      phage particle.

PMID- 12498797
TI  - Crystal structure and site-directed mutagenesis of enzymatic components from
      Clostridium perfringens iota-toxin.
AB  - Iota-toxin from Clostridium perfringens type E is an ADP-ribosylating toxin
      (ADPRT) that ADP-ribosylates actin, which is lethal and dermonecrotic in mammals.
      It is a binary toxin composed of an enzymatic component (Ia) and a binding
      component (Ib). Ia ADP-ribosylates G-actin at arginine 177, resulting in the
      depolymerization of the actin cytoskeleton. Here, we report on studies of the
      structure-function relationship by the crystal structures of Ia complexed with
      NADH and NADPH (at 1.8 A and 2.1 A resolution, respectively) and mutagenesis that
      map the active residues. The catalytic C-domain structure was similar to that of
      Bacillus cereus vegetative insecticidal protein (VIP2), which is an insect
      targeted toxin, except for the EXE loop region. However, a significant structural
      difference could be seen in the N-domain, which interacts with Ib, suggesting an
      evolutionary difference between mammalian-targeted and insect-targeted ADPRT. The
      high resolution structure analysis revealed specific NAD conformation (a ring
      like conformation of nicotinamide mononucleotide (NMN)) supported by Arg295,
      Arg296, Asn335, Arg352 and Glu380. Additionally, the mutagenesis study showed
      that the residues Tyr251, Arg295, Glu301, Ser338, Phe349, Arg352 and Glu380,
      including a newly identified one, are essential for NAD(+)-glycohydrolase
      (NADase) activity. At least one residue, Glu378, is an essential residue for ADP
      ribosyltransferase (ARTase), but not for NADase. Consequently, the structural
      feature and these mutagenesis findings suggest that the catalytic mechanism of Ia
      proceeds via an Sn1-type reaction.

PMID- 12498798
TI  - The structure of the aquaporin-1 water channel: a comparison between cryo
      electron microscopy and X-ray crystallography.
AB  - Three different medium-resolution structures of the human water channel aquaporin
      1 (AQP1) have been solved by cryo-electron microscopy (cryo-EM) during the last
      two years. Recently, the structure of the strongly related bovine AQP1 was solved
      by X-ray crystallography at higher resolution, allowing a validation of the
      original medium-resolution structures, and providing a good indication for the
      strengths and limitations of state of the art cryo-EM methods. We present a
      detailed comparison between the different models, which shows that overall, the
      structures are highly similar, deviating less than 2.5 A from each other in the
      helical backbone regions. The two original cryo-EM structures, however, also show
      a number of significant deviations from the X-ray structure, both in the backbone
      positions of the transmembrane helices and in the location of the amino acid side
      chains facing the pore. In contrast, the third cryo-EM structure that included
      information from the X-ray structure of the homologous bacterial glycerol
      facilitator GlpF and that was subsequently refined against cryo-EM AQP1 data,
      shows a root mean square deviation of 0.9A from the X-ray structure in the
      helical backbone regions.

PMID- 12498799
TI  - DsbA and DsbC-catalyzed oxidative folding of proteins with complex disulfide
      bridge patterns in vitro and in vivo.
AB  - Oxidative protein folding in the periplasm of Escherichia coli is catalyzed by
      the thiol-disulfide oxidoreductases DsbA and DsbC. We investigated the catalytic
      efficiency of these enzymes during folding of proteins with a very complex
      disulfide pattern in vivo and in vitro, using the Ragi bifunctional inhibitor
      (RBI) as model substrate. RBI is a 13.1 kDa protein with five overlapping
      disulfide bonds. We show that reduced RBI can be refolded quantitatively in
      glutathione redox buffers in vitro and spontaneously adopts the single correct
      conformation out of 750 possible species with five disulfide bonds. Under
      oxidizing redox conditions, however, RBI folding is hampered by accumulation of a
      large number of intermediates with non-native disulfide bonds, while a
      surprisingly low number of intermediates accumulates under optimal or reducing
      redox conditions. DsbC catalyzes folding of RBI under all redox conditions in
      vitro, but is particularly efficient in rearranging buried, non-native disulfide
      bonds formed under oxidizing conditions. In contrast, the influence of DsbA on
      the refolding reaction is essentially restricted to reducing redox conditions
      where disulfide formation is rate limiting. The effects of DsbA and DsbC on
      folding of RBI in E.coli are very similar to those observed in vitro. Whereas
      overexpression of DsbA has no effect on the amount of correctly folded RBI, co
      expression of DsbC enhanced the efficiency of RBI folding in the periplasm of
      E.coli about 14-fold. Addition of reduced glutathione to the growth medium
      together with DsbC overexpression further increased the folding yield of RBI in
      vivo to 26-fold. This shows that DsbC is the bacterial enzyme of choice for
      improving the periplasmic folding yields of proteins with very complex disulfide
      bond patterns.

PMID- 12498800
TI  - Three-dimensional structure-activity relationship modeling of cocaine binding to
      two monoclonal antibodies by comparative molecular field analysis.
AB  - Successful immunotherapy of cocaine addiction and overdoses requires cocaine
      binding antibodies with specific properties, such as high affinity and
      selectivity for cocaine. We have determined the affinities of two cocaine-binding
      murine monoclonal antibodies (mAb: clones 3P1A6 and MM0240PA) for cocaine and its
      metabolites by [3H]-radioligand binding assays. mAb 3P1A6 (K(d) = 0.22 nM)
      displayed a 50-fold higher affinity for cocaine than mAb MM0240PA (K(d) = 11 nM)
      and also had a greater specificity for cocaine. For the systematic exploration of
      both antibodies' binding specificities, we used a set of approximately 35 cocaine
      analogues as structural probes by determining their relative binding affinities
      (RBAs) using an enzyme-linked immunosorbent competition assay. Three-dimensional
      quantitative structure-activity relationship (3D-QSAR) models on the basis of
      comparative molecular field analysis (CoMFA) techniques correlated the binding
      data with structural features of the ligands. The analysis indicated that despite
      the mAbs' differing specificities for cocaine, the relative contributions of the
      steric (approximately 80%) and electrostatic (approximately 20%) field
      interactions to ligand-binding were similar. Generated three-dimensional CoMFA
      contour plots then located the specific regions about cocaine where the
      ligand/receptor interactions occurred. While the overall binding patterns of the
      two mAbs had many features in common, distinct differences were observed about
      the phenyl ring and the methylester group of cocaine. Furthermore, using
      previously published data, a 3D-QSAR model was developed for cocaine binding to
      the dopamine reuptake transporter (DAT) that was compared to the mAb models.
      Although the relative steric and electrostatic field contributions were similar
      to those of the mAbs, the DAT cocaine-binding site showed a preference for
      negatively charged ligands. Besides establishing molecular level insight into the
      interactions that govern cocaine binding specificity by biopolymers, the three
      dimensional images obtained reflect the properties of the mAbs binding pockets
      and provide the initial information needed for the possible design of novel
      antibodies with properties optimized for immunotherapy.

PMID- 12498801
TI  - Biophysical properties of human antibody variable domains.
AB  - There are great demands on the stability, expression yield and resistance to
      aggregation of antibody fragments. To untangle intrinsic domain effects from
      domain interactions, we present first a systematic evaluation of the isolated
      human immunoglobulin variable heavy (V(H)) and light (V(L)) germline family
      consensus domains and then a systematic series of V(H)-V(L) combinations in the
      scFv format. The constructs were evaluated in terms of their expression behavior,
      oligomeric state in solution and denaturant-induced unfolding equilibria under
      non-reducing conditions. The seven V(H) and seven V(L) domains represent the
      consensus sequences of the major human germline subclasses, derived from the
      Human Combinatorial Antibody Library (HuCAL). The isolated V(H) and V(L) domains
      with the highest thermodynamic stability and yield of soluble protein were V(H)3
      and V(kappa)3, respectively. Similar measurements on all domain combinations in
      scFv fragments allowed the scFv fragments to be classified according to
      thermodynamic stability and in vivo folding yield. The scFv fragments containing
      the variable domain combinations H3kappa3, H1bkappa3, H5kappa3 and H3kappa1 show
      superior properties concerning yield and stability. Domain interactions diminish
      the intrinsic differences of the domains. ScFv fragments containing V(lambda)
      domains show high levels of stability, even though V(lambda) domains are
      surprisingly unstable by themselves. This is due to a strong interaction with the
      V(H) domain and depends on the amino acid sequence of the CDR-L3. On the basis of
      these analyses and model structures, we suggest possibilities for further
      improvement of the biophysical properties of individual frameworks and give
      recommendations for library design.

PMID- 12498802
TI  - Structural details, pathways, and energetics of unfolding apomyoglobin.
AB  - Protein folding is often difficult to characterize experimentally because of the
      transience of intermediate states, and the complexity of the protein-solvent
      system. Atomistic simulations, which could provide more detailed information,
      have had to employ highly simplified models or high temperatures, to cope with
      the long time scales of unfolding; direct simulation of folding is even more
      problematic. We report a fully atomistic simulation of the acid-induced unfolding
      of apomyoglobin in which the protonation of acidic side-chains to simulate low pH
      is sufficient to induce unfolding at room temperature with no added biasing
      forces or other unusual conditions; and the trajectory is validated by comparison
      to experimental characterization of intermediate states. Novel insights provided
      by their analysis include: characterization of a dry swollen globule state
      forming a barrier to initial unfolding or final folding; observation of
      cooperativity in secondary and tertiary structure formation and its explanation
      in terms of dielectric environments; and structural details of the intermediate
      and the completely unfolded states. These insights involve time scales and levels
      of structural detail that are presently beyond the range of experiment, but come
      within reach through the simulation methods described here. An implicit solvation
      model is used to analyze the energetics of protein folding at various pH and
      ionic strength values, and a reasonable estimate of folding free energy is
      obtained. Electrostatic interactions are found to disfavor folding.

PMID- 12498803
TI  - AFM characterization of tilt and intrinsic flexibility of Rhodobacter sphaeroides
      light harvesting complex 2 (LH2).
AB  - Atomic force microscopy (AFM) has developed into a powerful tool to investigate
      membrane protein surfaces in a close-to-native environment. Here we report on the
      surface topography of Rhodobacter sphaeroides light harvesting complex 2 (LH2)
      reconstituted into two-dimensional crystals. These photosynthetic trans-membrane
      proteins formed cylindrical oligomeric complexes, which inserted tilted into the
      lipid membrane. This peculiar packing of an integral membrane protein allowed us
      to determine oligomerization and tilt of the LH2 complexes, but also protrusion
      height and intrinsic flexibility of their individual subunits. Furthermore the
      surface contouring reliability and limits of the atomic force microscopy could be
      studied. The two-dimensional crystals examined had sizes of up to 5 microm and,
      as revealed by a 10 A cryo electron microscopy projection map, p22(1)2(1) crystal
      symmetry. The unit cell had dimensions of a = b = 150 A and gamma = 90 degrees,
      and housed four nonameric complexes, two pointing up and two pointing down. AFM
      topographs of these 2D crystals had a lateral resolution of 10 A. Further, the
      high vertical resolution of approximately 1 A, allowed the protrusion height of
      the cylindrical LH2 complexes over the membrane to be determined. This was
      maximally 13.1 A on one side and 3.8 A on the other. Interestingly, the
      protrusion height varied across the LH2 complexes, showing the complexes to be
      inserted with a 6.2 degree tilt with respect to the membrane plane. A detailed
      analysis of the individual subunits showed the intrinsic flexibility of the
      membrane protruding peptide stretches to be equal and independent of their
      protrusion height. Furthermore, our analysis of membrane proteins within this
      peculiar packing confirmed the high vertical resolution of the atomic force
      microscopy on biological samples, and led us to conclude that the image
      acquisition function was equally accurate for contouring protrusions with heights
      up to approximately 15 A.

PMID- 12498804
TI  - In vitro and in silico design of alpha1-antitrypsin mutants with different
      conformational stabilities.
AB  - Alpha(1)-antitrypsin, a protein belonging to the serine protease inhibitor
      (serpin) superfamily, is characterized by the ability to undergo dramatic
      conformational changes leading to inactive polymers. Serpin polymerization, which
      causes a range of diseases such as emphysema, thrombosis and dementia, occurs
      through a process in which the reactive center loop residues of one serpin
      molecule insert into the A beta-sheet of another. PoPMuSiC, a program that uses
      database-derived mean force potentials to predict changes in folding free energy
      resulting from single-site mutations, was used to modulate rationally the
      polymerization propensity of alpha(1)-antitrypsin. This was accomplished by
      generating mutants with a stabilized active form and destabilized polymerized
      form, or the converse. Of these mutants, five were expressed and characterized
      experimentally. In agreement with the predictions, three of them, K331F, K331I
      and K331V, were shown to stabilize the active form and decrease the
      polymerization rate, and one of them, S330R, to destabilize the active form and
      to increase polymerization. Only one mutant (K331T) did not display the expected
      behavior. Thus, strikingly, the adjacent positions 330 and 331, which are located
      at the beginning of the beta-strand next to the additionally inserted beta-strand
      in the polymerized form, have opposite effects on the conformational change.
      These residues therefore appear to play a key role in inducing or preventing such
      conformational change.

PMID- 12498805
TI  - Antibody-cytokine fusion proteins: harnessing the combined power of cytokines and
      antibodies for cancer therapy.

PMID- 12498806
TI  - Lymphocytes expressing alpha1beta1 integrin (very late antigen-1) in peripheral
      blood of patients with arthritis are a subset of CD45RO(+) T-cells primed for
      rapid adhesion to collagen IV.
AB  - We report that very late antigen-1 (VLA-1(+)) CD3(+)CD45RO(+) T-cells are
      selectively segregated from VLA-1(-) peripheral blood (PB) mononuclear cells
      (MC), in which CD3(+) T-cells are evenly CD45RO(+) and CD45RO(-), when PBMC are
      stained with a monoclonal antibody (mAb) to VLA-1 and passaged on immunomagnetic
      columns. In contrast, both VLA-1(+) and VLA-1(-) MC isolated from synovial fluid
      (SF) are mainly CD45RO(+)CD3(+) T-cells. VLA-1(+) MC formed 13 +/- 5.3% of MC
      eluting from columns loaded with PBMC of patients with seropositive rheumatoid
      arthritis (n = 6) and 2.3 +/- 1.6% of patients (n = 4) with other arthritides (P
      < 0.022). Importantly, only the VLA-1(+) MC from PB and SF adhered to collagen IV
      upon triggering with phorbol 12-myristate 13-acetate. Moreover, adhesion and
      migration on collagen IV were preferentially maintained in lines cultured from
      VLA-1(+) T-cells, and both were inhibited by mAb to the VLA-1 alpha1 I domain.
      These results suggest that VLA-1(+) CD45RO(+) T-cells in patients with arthritis
      could play a role in both systemic and local inflammation by rapidly adhering to
      collagen IV.

PMID- 12498807
TI  - A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28
      antibodies enables rapid expansion and long-term growth of CD4 T lymphocytes.
AB  - We compared the ability of two genetically modified myeloid cells, K562 and U937,
      to serve as artificial antigen-presenting cells (aAPC). Both aAPC were stably
      transfected with the low-affinity Fcgamma receptor CD32 (K32/U32 cells). K32
      cells loaded with anti-CD3 and anti-CD28 Ab (K32/CD3/28) induced more rapid CD4 T
      cell expansion than CD3/28-coated beads. In contrast, U32/CD3/28 induced high
      levels of CD4 T-cell thymidine uptake but were unable to sustain long-term T-cell
      expansion. K32 cells, but not U32 cells, loaded with anti-CD3 alone also
      stimulated CD4 T-cell growth and IL-2 secretion, indicating the expression of
      additional costimulatory molecules on K32 cells. We found constitutive expression
      of B7-H3 and a strong upregulation of mRNA encoding for IL-15, PD-L1, and PD-L2
      after coculture with CD4 T cells activated by K32/CD3/28 but not U32/CD3/28. We
      conclude that K32 aAPCs are a robust system for clinical scale ex vivo expansion
      of CD4 T cells.

PMID- 12498808
TI  - Diminished T cell numbers in patients with chronic granulomatous disease.
AB  - Chronic granulomatous disease is a neutrophil disorder in which phagocytic cells
      fail to produce a respiratory burst. Five genetic types of chronic granulomatous
      disease have been described and in each case the clinical manifestations relate
      to the inability to effectively kill catalase-positive organisms. It is
      classically described as a pure disorder of intracellular killing, with
      preservation of other aspects of phagocytic function such as migration and
      phagocytosis and normal function of nonmyeloid cells. This article describes a
      heretofore unrecognized feature of chronic granulomatous disease. Fifty-three
      patients with chronic granulomatous disease and 42 age-matched controls were
      studied by flow cytometry. Total T cell numbers and CD4 and CD8 T cell numbers
      were compared between patients and controls. Patients with chronic granulomatous
      disease had diminished T cell numbers compared to controls after 3 years of age.
      The difference increased with age. It is not known whether diminished T cell
      numbers influence the susceptibility to infections in these patients, but T cell
      effects could represent a significant cofactor for infection.

PMID- 12498809
TI  - Serum concentration of gammaGT is a surrogate marker of hepatic TNF-alpha mRNA
      expression in chronic hepatitis C.
AB  - Serum gammaGT levels and hepatic expression of tumor necrosis factor-alpha (TNF
      alpha) are host factors that can independently predict the outcome of interferon
      (IFN) treatment in patients with chronic hepatitis C virus (HCV) infection. To
      explore whether a correlation exists between these two factors, we measured
      pretreatment gammaGT levels in serum and TNF-alpha mRNA levels in liver biopsies
      of chronic HCV patients. Seventy-two HCV patients treated with 3-to-5 million
      units of IFN-alpha three times a week were enrolled in the study. Treatment
      lasted 24 weeks and was followed by a 48-week follow-up period. Efficacy was
      assessed by measuring HCV RNA and alanine aminotransferase by the end of follow
      up. Twelve patients (16.6%) showed a sustained biochemical and virological
      response. Normal pretreatment gammaGT levels, low HCV RNA titer, and infection
      with genotype other than HCV-1 were shown to be independent predictors of
      sustained response. Hepatic levels of TNF-alpha mRNA, quantified by polymerase
      chain reaction, were significantly higher in nonresponders (3.44 arbitrary units)
      compared to sustained responders (1.84 arbitrary units; P = 0.009). Values
      </=3.12 arbitrary units independently predicted a sustained response to IFN (P =
      0.014). Finally, TNF-alpha mRNA levels were significantly correlated with serum
      gammaGT levels (r = 0.79, P < 0.0001). These findings suggest that serum gammaGT
      levels may represent a surrogate marker of hepatic TNF-alpha expression, thus
      explaining the importance of serum gammaGT levels in predicting treatment
      outcome.

PMID- 12498810
TI  - Dysfunctional and short-lived subsets in monocyte-derived dendritic cells from
      patients with advanced cancer.
AB  - Dendritic cells (DCs) are antigen-presenting cells specialized for the induction
      of the primary T-cell response. Tumor immunotherapy using DCs loaded with tumor
      antigens is under way for patients with several types of advanced malignancies.
      In this study, DC-like cells (Mo-DCs) were generated from peripheral blood
      monocytes with granulocyte-macrophage colony-stimulating factor and interleukin
      4. The antigen-presenting abilities, including capture of apoptotic tumor cells,
      IL-12 secretion, expression of antigen-presentation-related molecules (HLA-ABC,
      HLA-DR, and CD80), and mixed leukocyte reaction, of Mo-DCs from 37 patients with
      advanced cancer (pMo-DCs) were compared to those of 20 healthy volunteers (hMo
      DCs). Seven days after the initial culture, no significant difference was found
      in either the number or the size of Mo-DC-forming colonies between the two
      groups. However, most of the antigen-presenting abilities of pMo-DCs were weaker
      than those of hMo-DCs on day 7. On day 14, both number and size of colonies were
      significantly decreased in pMo-DCs but not in hMo-DCs. Interestingly, the antigen
      presenting abilities of the remaining pMo-DCs gradually strengthened with time
      and by day 14 no significant difference was observed between pMo-DCs and hMo-DCs.
      These results indicate that pMo-DCs contain dysfunctional and short-lived Mo-DC
      subsets.

PMID- 12498811
TI  - Dendritic cells are decreased in blood and accumulated in granuloma in
      tuberculosis.
AB  - Immunity against tuberculosis consists of innate and adaptive immune responses.
      In this study, we investigated the dynamics of dendritic cells (DC), which are
      known to elicit a variety of immune responses, in patients with tuberculosis.
      CD11c(+) peripheral blood DC were decreased in patients with tuberculosis.
      Immunohistochemical analyses demonstrated that a number of fascin(+), CD11c(+),
      HLA-DR(+) DC were infiltrating the lymphocyte areas of the tuberculous granulomas
      (tubercles). Immunohistochemical analyses also demonstrated that interferon-gamma
      producing Th1 cells were increased in the tubercles of the patients, indicating
      the presence of Th1 polarization at least in the context of inflammatory tissues.
      In vitro coculture of autologous naive T cells with CD11c(+) or CD11c(-) DC
      pretreated with Bacillus Calmette Guerin augmented the production of Th1 cells.
      These findings suggested that the trafficking of DC from the peripheral blood
      into the tubercles causes a dominant Th1 balance and thus plays an essential role
      in the immunity against tuberculosis.

PMID- 12498812
TI  - Retroviral gene therapy of collagen-induced arthritis by local delivery of IL-4.
AB  - Rheumatoid arthritis (RA) is an autoimmune arthritis, for which treatment options
      remain limited. This study investigated the potential role of adoptive cellular
      gene therapy as a novel means for treating the RA animal model collagen-induced
      arthritis (CIA). Adoptive transfer of antigen-specific T-cell hybridomas
      retrovirally transduced to express IL-4 1 day before booster immunization
      significantly reduced the number of inflamed joints. Cell transfer after clinical
      onset of disease had no therapeutic effect. Bioluminescence imaging showed that
      the hybridomas migrated to the inflamed joints, thus delivering the regulatory
      protein locally at the site of inflammation. The homing was, at least in part,
      due to chemotaxis in response to proinflammatory chemokines that are expressed in
      inflamed joints. There were no significant changes in the cytokine milieu of the
      draining lymph nodes, nor in the systemic levels of anti-collagen antibodies in
      treated mice. We conclude that the beneficial clinical effects observed in our
      model were most likely based on the local action(s) of IL-4 in the inflamed
      joints and that the local delivery (and effects) of regulatory cytokines, like IL
      4, constitutes a novel and effective method of preventing organ-specific
      autoimmune disease and of minimizing systemic adverse effects.

PMID- 12498813
TI  - Phenotypic characterization of inflammatory cells from osteoarthritic synovium
      and synovial fluids.
AB  - Osteoarthritis (OA) is considered a degenerative joint disorder caused by
      mechanical wear to the articular surface. However, while joint injury, obesity,
      and mutations in collagen increase the risk of developing OA, evidence implicates
      inflammatory mechanisms in disease progression and chronicity. To address this
      question we used FACS analysis, immunohistochemistry, and in vitro cell culture
      to evaluate inflammatory mechanisms in synovial fluids and joint tissues obtained
      after arthrocentesis or knee replacement surgery. Immunohistochemistry revealed a
      significant T cell infiltrate in six of nine tissue specimens. T cells were
      present throughout the synovial membrane and were particularly localized around
      vasculature and in large cellular aggregates. Cells within the aggregates
      expressed markers associated with immune activation and antigen presentation. T
      cells from OA synovial fluids expressed an activated phenotype and synthesized
      interferon-gamma following in vitro stimulation. These data support the
      hypothesis that inflammatory cells play a significant role in OA disease
      progression and chronicity.

PMID- 12498814
TI  - Oral recombinant Mycobacterium bovis bacillus Calmette-Guerin expressing HIV-1
      antigens as a freeze-dried vaccine induces long-term, HIV-specific mucosal and
      systemic immunity.
AB  - Induction of HIV-1-specific immune responses was evaluated using a recombinant
      BCG (rBCG) vector-based vaccine expressing HIV-1 Env V3 peptide (rBCG-pSOV3J1).
      rBCG-pSOV3J1 was manufactured as a freeze-dried preparation based on good
      laboratory practice guidelines. Guinea pigs were immunized with the freeze-dried
      rBCG vaccine by oral administration to test the effectiveness of what is
      generally considered the most convenient and practical route for vaccination.
      While delayed-type hypersensitivity (DTH) skin reactions to purified protein
      derivative were not detected in any of the animals receiving oral rBCG-pSOV3J1,
      HIV-1 V3J1 antigen-specific DTH responses were detected in all of the immunized
      guinea pigs 1.5 years after immunization. In addition, significant proliferative
      responses against HIV-1 V3J1 antigen were measured in peripheral blood
      mononuclear cells and splenocytes from all animals receiving oral rBCG.
      Interestingly, intestinal intraepithelial lymphocytes from the animals also
      exhibited high levels of proliferative activity against HIV-1 V3J1 antigen. These
      results suggest that oral vaccination of guinea pigs with freeze-dried rBCG
      pSOV3J1 induces high levels of functional T cells specific for HIV-1 antigens in
      both mucosal and systemic compartments and suggest that this approach has
      potential for use as a vaccine against HIV-1.

PMID- 12498815
TI  - During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell
      population comprises multiple antigenic specificities.
AB  - In the NOD mouse model of type 1 diabetes, major histocompatibilitycomplex (MHC)
      class I-restricted CD8(+) T cells are essential for disease development. However,
      the extent of diversity of their antigenic specificities during early
      pathogenesis remains unclear. An insulin-derived peptide was recently identified
      as the epitope for the NOD-derived diabetogenic T-cell clone G9C8. To explore the
      possibility that the early pathogenic CD8(+) T-cell population comprises
      additional antigenic specificities, we employed the T-cell clones AI4 and NY8.3,
      both of which are pathogenic and represent specificities present in early
      insulitic lesions. The clones responded to distinct fractions of
      chromatographically separated class I MHC-bound peptides purified from NOD
      derived NIT-1 beta cells, and neither clone recognized the insulin-derived
      peptide. NIT-1 cells represent an unlimited peptide source that will allow for
      the future isolation and sequencing of the novel multiple epitopes targeted early
      in the autoimmune response by pathogenic CD8(+) T cells.

PMID- 12498816
TI  - Anti-GM-CSF titer predicts response to GM-CSF therapy in pulmonary alveolar
      proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is an idiopathic disease characterized by
      the accumulation of surfactant in the pulmonary airspaces. The development of a
      PAP-like syndrome in the GM-CSF knockout mouse and resolution of disease by local
      GM-CSF expression strongly implicates GM-CSF in surfactant homeostasis and
      disease pathogenesis. Based on murine data, GM-CSF therapy was administered to
      PAP patients, with a subset responding to therapy. The lack of response to GM-CSF
      therapy in some patients is unexplained. In adult idiopathic PAP there appears to
      be no intrinsic cellular defect in synthesizing or secreting GM-CSF and/or
      function in the GM-CSF receptor. Subsequent studies have shown the presence of
      circulating, neutralizing anti-GM-CSF antibodies in all adult PAP patients
      studied to date. Whether the anti-GM-CSF is causally related to the PAP disease
      and whether it should be the target of manipulation remains to be determined. The
      present study quantified the anti-GM-CSF levels sequentially in PAP patients
      receiving GM-CSF therapy. The data indicate that titers of circulating anti-GM
      CSF predict response to GM-CSF therapy. In addition, we present data from a
      patient undergoing plasmapheresis in which anti-GM-CSF titer decreased with
      improvement in the lung disease. Together, these data support the hypothesis that
      PAP is an anti-GM-CSF autoimmune disease due to the development of antibodies,
      which results in the deactivation or neutralization of GM-CSF.

PMID- 12498817
TI  - Streptococcal cell wall arthritis: kinetics of immune cell activation in
      inflammatory arthritis.
AB  - The streptococcal cell wall model of arthritis in Lewis rats consists of an
      acute, non-T-cell-dependent initiation phase, followed by a remission and then a
      chronic, inflammatory T-cell-dependent phase. In this report, we define pertinent
      changes in the cognate and noncognate immune system of the Lewis rats during
      various phases of the disease. We examined changes in the population size of
      various cell types using lineage-specific markers in three different tissues
      (blood, spleen, and lymph nodes) over 28 days. Our results indicate that the T
      cell and monocyte populations were significantly altered in PG-PS-treated rats
      and the activation status of these cells parallel initiation, remission, and
      chronic phases of joint inflammation. Activation of B cells also increases in
      certain tissues in the chronic phase of the disease. In summary, our results
      confirm the involvement of both innate and cognate immunity in the development of
      arthritis and demonstrate that monocytes, in addition to T cells, play a
      substantive role in the induction and maintenance of the inflammatory process in
      this rat model.

PMID- 12498818
TI  - A combination therapy using IL-12 and soluble IL-4 receptor on herpes simplex
      virus Type 1 infection in a human-SCID chimera model of thermal injury.
AB  - Herpes simplex virus type 1 (HSV-1) is a severe pathogen in thermally injured
      patients. Type 1 T cells are essential for the host's anti-HSV protective
      immunity. Type 2 cytokines, commonly detected in thermally injured patients, have
      been described as inhibitors for the type 1 T cell generation. Therefore, the
      antiviral effects of combination therapy with a type 1 T cell inducer
      [interleukin (IL)-12] and a type 2 T cell inhibitor [soluble IL-4 receptor (sIL
      4R)] were investigated in severe combined immunodeficiency (SCID) mice inoculated
      with peripheral blood lymphocytes (PBL) of thermally injured patients. Patient
      PBL-SCID chimeras (SCID mice inoculated with patient PBL) were susceptible to
      infection with 1 x 10(3) PFU/kg of HSV-1 (0% survival), while healthy PBL-SCID
      chimeras (SCID mice inoculated with PBL from healthy donors) were resistant (92%
      survival). When patient PBL-SCID chimeras exposed to HSV-1 were treated with
      saline, human recombinant (r) IL-12 or human sIL-4R, 0, 0, or 12.5% of them
      survived, respectively. However, 75% of these chimeras survived when they were
      treated with rIL-12 and sIL-4R in combination. These results indicate that HSV-1
      infection in patient PBL-SCID chimeras was therapeutically controlled by the
      inducer of type 1 T cell responses and the inhibitor of type 2 T cell responses
      in combination.

PMID- 12498819
TI  - Iatrogenic keratectasia: current knowledge, current measurements.

PMID- 12498820
TI  - Big bubble technique in anterior lamellar keratoplasty.

PMID- 12498822
TI  - Prevention of capsular block syndrome.

PMID- 12498824
TI  - Silicone oil bubbles in ophthalmic viscosurgical devices.

PMID- 12498825
TI  - Noncontact tonometry after LASIK.

PMID- 12498826
TI  - Heparin in the irrigation solution during cataract surgery.

PMID- 12498827
TI  - Comparison of prophylactic measures.

PMID- 12498828
TI  - Consultation section: cataract surgical problem.

PMID- 12498840
TI  - Transition to nonpenetrating trabecular surgery: sclerotrabeculectomy.
AB  - A transition from trabeculectomy to nonpenetrating trabecular surgery (NPTS) is
      proposed under the name of sclerotrabeculectomy. The technique, which is aimed at
      facilitating the transition to NPTS, is a modification of both penetrating and
      nonpenetrating techniques. Sclerotrabeculectomy uses a more superficial
      sclerokeratectomy than NPTS to avoid the risk of perforation. A
      minitrabeculectomy with cross-linked hyaluronate implant insertion in the
      sclerokeratectomy site is performed, with several sutures placed in the
      superficial flap. The sclerokeratectomy site is filled with cohesive viscoelastic
      substance to avoid a flat or shallow anterior chamber. Using this technique, it
      is possible to move to NPTS by finding the pre-Descemet's plane in front of the
      scleral spur and removing the external trabeculum. In case of accidental
      microperforation of Descemet's plane, the operation is finished as a standard
      sclerotrabeculectomy with no risk to the patient's eye. A safe transition can
      thus be achieved. Initial clinical results demonstrate excellent lowering of
      intraocular pressure without significant complications.

PMID- 12498841
TI  - Posterior chamber intraocular lens supported by an intact vitreous face.
AB  - We describe a technique of posterior chamber intraocular lens (IOL) implantation
      in eyes with inadequate capsule support caused by inadvertent or planned
      intracapsular cataract extraction (ICCE) or in eyes having secondary IOL
      implantation after previous ICCE. The procedure is only performed in eyes with an
      intact anterior vitreous face, no vitreous prolapse into the anterior chamber,
      and no vitreous loss. The anterior vitreous is pushed back by viscoelastic
      material or air. The viscoelastic material is injected under the iris to create a
      free space between the iris and anterior vitreous. A single-piece, C-loop,
      poly(methyl methacrylate) IOL is slid onto the iris to rest on the anterior
      vitreous face; care is taken not to disturb the anterior vitreous. The technique
      was used in 15 eyes with a follow-up from 19 months to 5 years. All eyes had a
      stable IOL at each follow-up, and the visual acuity was 6/12 or better at the
      last follow-up.

PMID- 12498842
TI  - Evaluation of the prophylactic use of mitomycin-C to inhibit haze formation after
      photorefractive keratectomy.
AB  - PURPOSE: To evaluate the results of the prophylactic use of mitomycin-C to
      inhibit haze formation after excimer laser photorefractive keratectomy (PRK) for
      medium and high myopia in eyes that were not good candidates for laser in situ
      keratomileusis (LASIK). SETTING: Carones Ophthalmology Center, Milan, Italy.
      METHODS: This prospective randomized masked study comprised 60 consecutive eyes
      (60 patients). The inclusion criteria were a spherical equivalent correction
      between -6.00 and -10.00 diopters (D) and inadequate corneal thickness to allow a
      LASIK procedure with a residual stromal thickness of more than 250 microm. The
      eyes were divided into 2 groups according to the randomization protocol. After
      PRK, the study group eyes were treated with a single intraoperative dose of
      mitomycin-C (0.2 mg/mL), applied topically with a soaked microsponge placed over
      the ablated area and maintained for 2 minutes. The control eyes did not receive
      this treatment. Refraction, uncorrected visual acuity (UCVA), best corrected
      visual acuity (BCVA), and slitlamp evidence of corneal opacity (haze) or other
      visible complications were evaluated. RESULTS: No toxic or side effects were
      encountered postoperatively. No study group eye had a haze rate higher than 1
      during the 6-month follow-up; 19 eyes (63%) in the control group did (P =.01). At
      6 months, the between-group difference in the refractive outcome was
      statistically significant (P =.05), with 26 study group eyes (87%) and 14 control
      eyes (47%) within +/-0.50 D of the attempted correction. No study group eye had a
      BCVA loss during the follow-up; 7 control eyes had lost 1 to 3 lines at 6 months
      (P =.0006). CONCLUSIONS: The prophylactic use of a diluted mitomycin-C 0.02%
      solution applied intraoperatively in a single dose after PRK produced lower haze
      rates, better UCVA and BCVA results, and more accurate refractive outcomes than
      those achieved in the control group.

PMID- 12498843
TI  - Comparative performance of intraocular lenses in eyes with cataract and uveitis.
AB  - PURPOSE: To evaluate the postoperative outcomes in uveitic eyes after
      phacoemulsification and posterior chamber intraocular lens (IOL) implantation.
      SETTING: Multicenter (19) international study. METHODS: This prospective
      randomized comparative interventional case series comprised 140 eyes of 140
      patients who had phacoemulsification and implantation of IOLs of various
      materials: hydrophobic acrylic (n = 48), silicone (n = 44), poly(methyl
      methacrylate) (PMMA) (n = 26), or heparin-surface-modified PMMA (HSM PMMA) (n =
      22). Preoperative and postoperative grading and control of intraocular
      inflammation were performed. Clinically significant observations, visual
      outcomes, and the incidence of postoperative complications were recorded.
      RESULTS: At the final follow-up, 64 eyes (46.3%) had a best corrected visual
      acuity of 20/40 or better, an improvement that was highly significant (P <.0001).
      One day after surgery, the acrylic group had the lowest inflammation values and
      the silicone group the highest (P =.02). The acrylic group continued to have the
      lowest inflammation grade values until the 3-month follow-up. The acrylic and HSM
      PMMA groups had the lowest incidence of relapses. Posterior capsule opacification
      developed in 48 eyes (34.2%), with the highest incidence in the silicone group.
      CONCLUSIONS: Phacoemulsification with IOL implantation in selected uveitic eyes
      was safe and effective. Acrylic IOLs provided a better visual outcome and lower
      complication rate than IOLs of other materials.

PMID- 12498844
TI  - Analyzing refractive data.
AB  - PURPOSE: To provide a general approach to the analysis of refractive data that
      overcomes the shortcomings of traditional treatments and can be easily adapted to
      most spreadsheets. SETTING: Corneal Service, Royal Liverpool Hospital, Liverpool
      United Kingdom, and Optometric Science Group, Rand Afrikaans University, Auckland
      Park, South Africa. METHOD: The basis of the analyses is the dioptric power
      matrix. Using a hypothetical sample of data on pre-event and post-event
      refractions, the calculation of the mean pre-event and post-event refractions and
      the effect of an event on the refractive outcome, for example the refractive
      surgical effect, are illustrated. The most important statistics, the mean and the
      variance-covariance of refractions, and the formal testing of hypotheses on the
      mean are provided. RESULTS: The method of analysis demonstrated how an event such
      as cataract surgery, occlusion treatment of amblyopia, or anisometropia can be
      evaluated in terms of refractive outcome. Hypothesis testing showed how the
      significance of this effect may be demonstrated. CONCLUSIONS: This standardized
      method of analyzing and reporting refractive data enables a quantitative analysis
      and statistical hypothesis testing of the complete refractive data. This approach
      has generalized applicability in a range of commonly encountered contexts such as
      the refractive change after cataract and refractive surgery, corneal
      transplantation, and treatment for amblyopia or the significance of
      anisometropia. The method is relatively straightforward and can be adapted to
      most conventional spreadsheets.

PMID- 12498845
TI  - Retinal nerve fiber layer thickness changes after an acute increase in
      intraocular pressure.
AB  - PURPOSE: To determine whether the increase in intraocular pressure (IOP) for 45
      seconds during laser in situ keratomileusis (LASIK) suction can induce a decrease
      in retinal nerve fiber layer thickness (RNFLT) assessed by a confocal scanning
      laser polarimeter. SETTING: Jules Gonin Hospital, University of Lausanne,
      Lausanne, Switzerland. METHODS: Eleven normal volunteers were enrolled in the
      study. The optic disc of each eye was analyzed by the GDx(R) Nerve Fiber Analyzer
      (Laser Diagnostic Technologies, Inc.), version 1.0.14. Using the standard circle
      that appears as a 10-pixel green circle on the GDx display, the system assessed
      the RNFLT at 1.75 disc diameter from the outer edge of the optic nerve head. To
      further evaluate the possible retinal nerve fiber layer (RNFL) loss, the 360
      degree circumference was divided into 36 segments measuring 10 degrees each and
      the RNFLT was calculated for each sector. All subjects had a GDx assessment
      before 100 mm Hg ocular compression of 1 eye for 45 seconds and then 2 minutes
      and 1 month after compression. RESULTS: Before compression, the mean RNFLT was
      69.09 microm +/- 10.96 (SD); it was 69.27 +/- 10.98 microm after 2 minutes and
      67.00 +/- 10.58 microm after 1 month. No statistically significant difference was
      found between the before and after measurements. CONCLUSION: A 45-second acute
      increase in IOP, such as during LASIK suction, did not decrease the RNFLT in
      normal eyes.

PMID- 12498846
TI  - Change in retinal nerve fiber layer thickness after laser in situ keratomileusis.
AB  - PURPOSE: To determine the effect of laser in situ keratomileusis (LASIK) on
      retinal nerve fiber layer (RNFL) dropout. SETTING: Nevyas Eye Associates,
      Philadelphia, Pennsylvania, USA. METHODS: This prospective consecutive study
      comprised 120 eyes. The GDx((R)) nerve fiber analyzer (Laser Diagnostic
      Technologies, Inc.) was used to measure RNFL thickness, an early indicator of
      glaucomatous damage, preoperatively and 1 week to 4 months and 6 months
      postoperatively to determine whether any change in apparent RNFL thickness was
      due to corneal change or to actual RNFL damage and to determine whether apoptotic
      cascade caused ongoing RNFL dropout. Humphrey visual fields were done in eyes
      with an abnormal GDx (increase of 20 in GDx number). RESULTS: The GDx was normal
      in 89 eyes, including 6 eyes with tilted discs, an abnormal number, and a normal
      image and 15 eyes with a nonprogressive increase in the GDx number. Three eyes,
      normal at the interim, were abnormal at 6 months but had a normal visual field.
      Eleven eyes had a significant increase in the number at 6 months, including 1 eye
      that showed a possible glaucomatous visual field defect at 9 months and a normal
      visual field at 14 months. CONCLUSIONS: There was no evidence of RNFL thinning or
      glaucomatous damage. A new baseline GDx should be established post LASIK to
      correct for corneal change.

PMID- 12498847
TI  - Frequency-doubling perimetry after photorefractive keratectomy.
AB  - PURPOSE: To evaluate the effect of photorefractive keratectomy (PRK) on frequency
      doubling perimetry (FDP) patterns in myopic patients without glaucoma. SETTING:
      Department of Ophthalmology, University of Bari, Bari, Italy. METHODS: Sixteen
      myopic patients (16 eyes) with a spherical equivalent worse than -7.0 diopters
      were enrolled. The fellow eyes were used as controls. All patients had PRK for
      myopia. Using FDP, the mean defect (MD) and pattern standard deviation (PSD) were
      evaluated preoperatively and 2 weeks and 3 and 6 months after PRK. At the same
      examinations, the effect of the reprofiled cornea on the visual field was
      studied; the cornea was divided into 4 concentric zones (central, paracentral,
      lateral, and peripheral) and each median zone contrast sensitivity (MZCS)
      evaluated. RESULTS: There was no difference in PSD and MZCS between treated eyes
      and controls in any zone at any time (P >.05). Longitudinally, there was no
      variation in any perimetry zone (P >.05). In treated eyes, there was a
      significant relationship among ablation depth, MD, and MZCS in all zones until 2
      weeks after laser surgery (P <.02). CONCLUSIONS: Frequency-doubling perimetry did
      not appear to be affected by corneal changes induced by PRK and can therefore be
      safely used in the early diagnosis of glaucoma.

PMID- 12498848
TI  - Repeatability and validity of Zywave aberrometer measurements.
AB  - PURPOSE: To study the repeatability of Zywave aberrometer (Bausch & Lomb)
      measurements and compare the measurements with those of subjective refraction and
      noncycloplegic and cycloplegic autorefractions in a clinical setting. SETTING:
      Department of Ophthalmology, University Hospital Maastricht, Maastricht, The
      Netherlands. METHODS: Subjective manifest refraction, noncycloplegic
      autorefraction, cycloplegic autorefraction, and Zywave aberrometer measurements
      were performed in 20 eyes of 20 myopic patients. Three consecutive Zywave
      measurements were performed with and without dilation of the pupil. The mean
      difference and 95% limits of agreement among the measurement methods were
      determined for dilated and 3.5 mm pupils. The repeatability coefficient of the
      Zywave aberrometer measurements was determined. RESULTS: The mean differences in
      spherical equivalent (SE), sphere, and cylinder between subjective refraction and
      Zywave predicted phoropter refraction (PPR) with a dilated pupil were -1.10
      diopters (D) +/- 0.46 (SD) (P <.001), -1.08 +/- 0.44 D (P <.001), and -0.02 +/-
      0.37 D (P =.87), respectively (paired Student t test). After the data were
      converted to a 3.5 mm pupil, the mean differences were -0.55 +/- 0.48 D (P
      <.001), -0.50 +/- 0.49 D (P <.001), and -0.16 +/- 0.50 D (P =.15), respectively.
      The mean difference in SE between autorefraction and cycloplegic autorefraction
      versus subjective refraction was +0.18 +/- 0.71 D (P =.27) and +0.35 +/- 0.62 D
      (P =.02), respectively. The mean difference in SE between cycloplegic
      autorefraction and Zywave PPR with a dilated pupil was -1.44 +/- 0.79 D (P
      <.001). The repeatability coefficient of Zywave PPR was +/-0.25 D for SE, +/-0.29
      D for sphere, and +/-0.29 D for cylinder. CONCLUSIONS: Subjective refraction
      measurements are slightly more myopic than cycloplegic autorefraction
      measurements. With a dilated pupil, the Zywave measurements were significantly
      more myopic than subjective refractions and even more myopic than cycloplegic
      autorefractions. Zywave measurements and subjective refractions were in better
      agreement with a 3.5 mm pupil. The repeatability of Zywave aberrometer
      measurements is adequate for lower-order aberrations.

PMID- 12498850
TI  - Mismatch between flap and stromal areas after laser in situ keratomileusis as
      source of flap striae.
AB  - PURPOSE: To calculate theoretically the magnitude of the excess area between the
      lower surface of the flap and the underlying ablated stroma. METHODS: On the
      initial assumptions of a nonextensible flap and a spherical cornea, flap and
      ablated stromal areas were determined as a function of myopic correction in the
      range of 0 to -12 diopters (D) for typical values of corneal radius (7.8 mm) and
      flap thickness (160 microm), together with a range of ablation zone diameters
      (4.0 mm, 6.0 mm, 8.0 mm, and 10.0 mm). RESULTS: Excess flap area increases with
      the magnitude of the refractive correction and the diameter of the ablated zone.
      For a -6.0 D correction and an 8.0 mm ablation zone, the excess area is nominally
      about 1.0 mm(2), giving a potential overlap of the flap at the edge opposite the
      hinge of about 100 microm. CONCLUSIONS; Excess flap area may cause striae because
      of wrinkling. Although a nonextensible flap is assumed in the model, any
      stretching or contraction due to cutting the flap will be independent of the
      refractive correction. Hence, a mismatch in areas must still occur. This
      geometric effect may have clinical consequences in optical aberration, refractive
      regression, or impaired wound healing.

PMID- 12498849
TI  - Comparison of ultrasound pachymetry and partial coherence interferometry in the
      measurement of central corneal thickness.
AB  - PURPOSE: To compare central corneal thickness (CCT) measurements obtained with 3
      ultrasound pachymeters and with partial coherence interferometry (PCI) and
      evaluate the effect of repeated contact by a pachymetry probe on corneal
      thickness. SETTING: Department of Ophthalmology, University of Vienna, Vienna,
      Austria. METHODS: Central corneal thickness was measured in 20 eyes of 20 healthy
      volunteers with 3 different ultrasound pachymeters (DGH 500, DGH Technology Inc.;
      SP 2000, Tomey Inc.; Paxis, Biovision Inc.) and with PCI. In each eye, 5
      measurements with PCI were followed by 5 measurements with each ultrasound
      pachymetry device and another 5 measurements with PCI. RESULTS: The mean CCT
      measured with the DGH 500, SP 2000, and Paxis was 541.0 microm, 539.2 microm, and
      545.1 microm, respectively. Although the differences among the 3 ultrasound
      pachymetry devices were within 6.0 microm, they were statistically significant
      (P<.05). The PCI measurements were significantly smaller (P <.05) than the
      ultrasound measurements: 518.8 microm before and 517.5 microm after repeated
      contact with the ultrasound pachymetry probe (P <.05). The mean precision
      (standard deviation) was 0.77 microm for PCI and between 2.40 microm and 3.58
      microm for ultrasound pachymetry measurements. The correlation coefficients for
      the intraobserver variability were 0.999 for PCI and between 0.987 and 0.995 for
      ultrasound pachymetry measurements. CONCLUSIONS: Partial coherence interferometry
      was the more precise method of measuring CCT and had better intraobserver
      variability. Repeated contact by a pachymetry probe reduced corneal thickness by
      1.3 microm. However, the reason for the smaller measurements with PCI than with
      ultrasound pachymetry remains unclear.

PMID- 12498851
TI  - Analyzing small-incision cataract surgery by Orbscan II fourth-dimensional
      pachymetry mapping.
AB  - PURPOSE: To assess the changes in pachymetry after routine corneal and scleral
      tunnel phacoemulsification. SETTING: Discipline of Ophthalmology, University of
      Auckland, Auckland, New Zealand. METHOD: This prospective study comprised 174
      eyes of 174 consecutive patients having uneventful, small-incision, sutureless,
      phacoemulsification cataract surgery; 124 patients had a clear corneal incision
      and 50, a superior scleral tunnel incision. Difference pachymetry maps were
      derived from Orbscan II elevation topography data obtained before and 4 weeks
      after surgery. Corneal thickness changes at 12 midperipheral areas located in 12
      meridians were derived from difference (subtraction) maps. The mean corneal
      thickness within a single area corresponding to the center of the surgical
      incision was compared to the mean pachymetry readings of all 12 midperipheral
      measurements. RESULTS: The overall mean midperipheral corneal thickness (12
      samples per cornea) increased by a mean of 5.89 microm +/- 16.09 (SD) in the
      clear corneal incision group and 6.89 +/- 14.50 microm in the scleral tunnel
      group. The mean central corneal thickness increased by 7.28 +/- 20.98 microm and
      7.74 +/- 21.34 microm, respectively. The corneal thickness in the meridian
      closest to the incision was significantly higher than the mean value of the 12
      meridians measured in both groups, with means of 14.95 +/- 26.86 microm in the
      clear corneal group (P =.001) and 16.22 +/- 21.23 microm in the scleral tunnel
      group (P =.002). There were no statistically significant postoperative
      differences in the central, midperipheral, or incision-site corneal thickness
      measurements between the 2 surgical techniques (P =.77). CONCLUSIONS: Time
      dependent (fourth-dimensional) pachymetry subtraction maps are useful for
      following corneal dynamics over time. This study found that small-incision
      phacoemulsification techniques--scleral and corneal tunnel--had a minor but
      similar effect on corneal thickness 4 weeks after surgery.

PMID- 12498852
TI  - Long-term effect of cataract surgery on intraocular pressure after
      trabeculectomy: extracapsular extraction versus phacoemulsification.
AB  - PURPOSE: To compare the effect of phacoemulsification with intraocular lens (IOL)
      implantation on long-term intraocular pressure (IOP) control in glaucoma patients
      who had previous trabeculectomy with the effect on IOP control in similar
      patients after extracapsular cataract extraction (ECCE) with IOL implantation.
      SETTING: Oxford Eye Hospital, Oxford, England. METHODS: Twenty-eight consecutive
      patients who had phacoemulsification with IOL implantation (phaco group) at least
      3 months after trabeculectomy were identified from hospital records, and 28
      patients who had ECCE with IOL implantation (ECCE group) were matched
      retrospectively to the phaco group with respect to age, sex, diagnosis, and IOP.
      In both groups, the IOP before cataract extraction was compared with the IOP at
      intervals up to 2 years after cataract extraction. A Kaplan-Meier survival
      analysis was performed. RESULTS: The mean IOP in the phaco group did not differ
      significantly from the mean IOP before cataract extraction at any interval.
      Twelve months after cataract extraction, the mean IOP in the ECCE group was
      significantly higher than preoperatively (P =.01); however, the mean IOP did not
      differ between groups over time (P =.704). There was significantly better long
      term IOP control in the phaco group as determined by Kaplan-Meier survival
      analysis and the log-rank test (P =.038). CONCLUSION: After trabeculectomy,
      phacoemulsification provided better long-term IOP control than ECCE; however, the
      mean IOP was not significantly lower.

PMID- 12498853
TI  - Phacoemulsification with indocyanine green versus manual expression extracapsular
      cataract extraction for advanced cataract.
AB  - PURPOSE: To compare the outcomes of indocyanine green dye (ICG)-assisted
      phacoemulsification with manual expression extracapsular cataract extraction
      (ECCE) in eyes with advanced cataract. SETTING: Parkland Memorial Hospital and
      Dallas Veterans Affairs Medical Center, Dallas, Texas, USA. METHODS: In this
      retrospective study, 72 consecutive cases of advanced or mature cataract
      extractions performed in a 1-year period were reviewed. Fifty-nine eyes met the
      inclusion and exclusion criteria; 33 had ICG-assisted phacoemulsification and 26,
      manual expression ECCE. Preoperative and intraoperative findings and the
      postoperative outcomes up to 6 months were analyzed. RESULTS: Intraoperative
      complications included posterior capsule tear with vitreous prolapse in 2 eyes
      (6.6%) and conversion to manual expression ECCE in 1 eye (3.3%) in the ICG
      phacoemulsification group. There was no intraoperative complication in the manual
      expression ECCE group. There were significantly more patients with a best
      corrected visual acuity of 20/30 or better in the ICG phacoemulsification group
      than in the manual expression ECCE group at all postoperative periods. The mean
      logMAR visual acuities were significantly better in the ICG phacoemulsification
      group at all postoperative intervals. The ICG phacoemulsification group had
      significantly less postoperative astigmatism. There was no significant difference
      between the groups in the early postoperative intraocular pressure. CONCLUSIONS:
      Phacoemulsification with ICG led to better postoperative visual acuity and less
      postoperative astigmatism than manual expression ECCE. Phacoemulsification with
      ICG was associated with more intraoperative complications than manual expression
      ECCE; however, the complication rate is comparable to a previously published rate
      for phacoemulsification performed in a university training program.
      Phacoemulsification with ICG appears to be a reasonable alternative to manual
      expression ECCE for advanced cataract.

PMID- 12498854
TI  - Pupil diameter changes and reaction after posterior chamber phakic intraocular
      lens implantation.
AB  - PURPOSE: To compare the different aspects of pupil constriction before and after
      the implantation of an implantable contact lens (ICL). SETTING: Augenabteilung
      der Schlosspark-Klinik Berlin, Berlin, Germany. METHODS: This study comprised 15
      myopic and 9 hyperopic eyes that were evaluated before and after the implantation
      of an ICL using a compact integrated pupillograph (CIP, AMTech) under
      standardized conditions. The preoperative and postoperative pupil diameters, rate
      and latency of the pupil reaction, and amplitude of constriction were compared.
      RESULTS: The latency and the duration of pupil constriction were significantly
      prolonged after ICL implantation. The rate of pupil contraction and redilation,
      the pupil diameter, and the amplitude of pupil constriction were reduced after
      ICL implantation. CONCLUSIONS: The pupil reaction after implantation of a phakic
      posterior chamber ICL was slower. The postoperative pupil diameter was smaller,
      and the amplitude of constriction was reduced. The changes have not proved to be
      clinically significant to date.

PMID- 12498855
TI  - Microbial contamination of the anterior chamber during phacoemulsification.
AB  - PURPOSE: To study the nature and frequency of anterior chamber contamination
      during phacoemulsification. SETTING: Department of Ophthalmology, Jawaharlal
      Institute of Postgraduate Medical Education and Research, Pondicherry, India.
      METHODS: Eighty eyes of 80 patients having routine phacoemulsification cataract
      surgery were recruited into this prospective study. Bacterial cultures from the
      intraoperative anterior chamber aspirates from the patients were assessed.
      RESULTS: Anterior chamber fluid aspirates were positive for bacteria in 37 eyes
      (46.25%). Coagulase-negative Staphylococcus was the most common aerobe and
      Propionibacterium acnes, the most common anaerobe. CONCLUSION: Results indicate
      that phacoemulsification has no proven advantage over conventional extracapsular
      cataract extraction in reducing intraoperative bacterial contamination.

PMID- 12498856
TI  - Preventing intraocular pressure increase after phacoemulsification and the role
      of perioperative apraclonidine.
AB  - PURPOSE: To evaluate the effectiveness of prophylactic topical apraclonidine 1%
      in preventing an intraocular pressure (IOP) rise in the early period after
      uneventful phacoemulsification with intraocular lens (IOL) implantation. SETTING:
      District general hospital, United Kingdom. METHODS: In this prospective masked
      randomized trial, 61 patients had elective, routine, corneal tunnel, sutureless
      phacoemulsification with in-the-bag foldable IOL implantation. A single surgeon
      operated on all the patients. Patients were randomized to receive topical
      apraclonidine 1% eyedrops (n = 31) or artificial tears (control group, n = 30) 1
      hour preoperatively and at the end of the surgery. An observer masked to the
      perioperative drops used measured the IOP preoperatively and 3 to 6 hours and 16
      to 24 hours postoperatively. The primary outcome was the change in IOP between
      the baseline and the 2 postoperative intervals. The IOP changes within and
      between the groups were analyzed using the t test and chi-square test. RESULTS:
      The changes between the postoperative and preoperative IOPs in the study groups
      were statistically significant (apraclonidine, P = 0.018 and P = 0.007,
      respectively; artificial tears, P = 0.028 and P = 0.023, respectively; paired t
      test). There was no significant difference in the postoperative IOP between the
      apraclonidine and control groups 3 to 6 hours and 16 to 24 hours postoperatively
      (P = 0.717 and P = 0.497, respectively; independent t test). The mean difference
      was 0.2 mm Hg (95% confidence interval [CI], -3.4 to 3.1) in the apraclonidine
      group and 2.2 mm Hg (95% CI, -2.5 to 7.0) in the control group. In each group, a
      few patients had an IOP greater than 30 mm Hg in the first 24 hours. CONCLUSION:
      Prophylactic topical perioperative apraclonidine 1% did not cause a significant
      reduction in the postoperative IOP when compared with a control group.

PMID- 12498857
TI  - Accuracy of Orbscan II slit-scanning elevation topography.
AB  - PURPOSE: To establish the accuracy of Orbscan II (Orbtek Inc.) slit-scanning
      elevation topography in analyzing the anterior surface of complex test objects.
      SETTING: Discipline of Ophthalmology, University of Auckland, Faculty of Medical
      and Health Sciences, Auckland, New Zealand. METHODS: Six test objects were
      created from 2 materials: standard calibration poly(methyl methacrylate) (PMMA)
      (Orbtek Inc.) and a research PMMA material. The test objects were produced with
      spherical (radii of curvature 6.00 mm, 7.67 mm, and 8.88 mm), aspherical (apical
      radius 7.67, eccentricity 0.5, Q -0.25), and toroidal (7.67/7.92 mm radii of
      curvature) surfaces. The accuracy of the test surfaces was established by Form
      Talysurf Analysis. A single calibrated Orbscan II device was used to obtain 20
      separate anterior elevation maps of each test object. The data obtained from
      Orbscan II, at 0.2 mm intervals along the chosen meridian, were directly compared
      with the Talysurf values for each test surface. RESULTS: Orbscan II measurements
      of all test objects were statistically significantly different from the Talysurf
      values (P <.001). The test objects produced from standard calibration material
      were more accurately measured by Orbscan II than the objects produced from the
      research material. Data obtained by Orbscan II from the central 3.5 mm of all
      test objects were more accurate than peripheral data when compared with the
      Talysurf values (P =.001). CONCLUSIONS: Orbscan II anterior surface elevation
      measurements differed significantly from Form Talysurf Analysis of complex test
      surfaces. However, the magnitude of the errors in the measurement of standard
      test objects was small, less than 0.20 microm centrally and 0.70 microm
      peripherally. Clinically, if similar accuracy of measurement is confirmed in the
      human eye, anterior surface elevation maps can be considered accurate
      representations of corneal shape.

PMID- 12498858
TI  - Nitric oxide levels in aqueous humor after lens extraction and poly(methyl
      methacrylate) and foldable acrylic intraocular lens implantation in rabbit eyes.
AB  - PURPOSE: To measure the nitric oxide (NO) level in the aqueous humor of rabbit
      eyes after common cataract surgery techniques. SETTING: Department of
      Ophthalmology, Military Medical University, and Department of Immunology and
      Immunotoxicology of Respiratory System, Clinic of Pneumonology and Allergology,
      Medical University of Lodz, Lodz, Poland. METHODS: Thirty rabbits were randomly
      divided into 4 groups, and surgery was performed as follows: Group 1,
      extracapsular cataract extraction (ECCE) and poly(methyl methacrylate) (PMMA)
      intraocular lens (IOL) implantation; Group 2, ECCE; Group 3, phacoemulsification
      and foldable acrylic IOL implantation; Group 4, phacoemulsification. The aqueous
      humor specimens were collected on days 1, 3, and 5. Nitric oxide measurements
      were performed indirectly with a spectrophotometer. The NO level in the aqueous
      humor collected before surgery served as a control group. RESULTS: In the
      physiological condition, the concentration of NO was 26.52 nm/dL +/- 4.86 (SD).
      Postoperatively, the highest NO level in each groups was as follows: Group 1,
      46.26 +/- 5.23 nm/dL on day 3; Group 2, 72.46 +/- 6.94 nm/dL on day 1; Group 3,
      41.04 +/- 7.31 nm/dL on day 1; and Group 4, 32.67 +/- 2.84 nm/dL on day 3.
      Significantly higher levels of NO (P <.05) were observed in Groups 1 and 2 at
      each follow-up day; in Group 3, on days 1 and 3; and in Group 4, on day 3.
      CONCLUSIONS: Techniques of cataract extraction caused the NO level to increase;
      however, phacoemulsification with a foldable IOL caused the smallest release of
      NO. Rapid postoperative NO changes may theoretically contribute to blood-aqueous
      barrier breakdown secondary to cataract surgery.

PMID- 12498859
TI  - Complications of foldable intraocular lenses requiring explantation or secondary
      intervention--2001 survey update.
AB  - A survey of the complications associated with foldable intraocular lenses (IOLs)
      that required explantation or secondary intervention was sent to members of the
      American Society of Cataract and Refractive Surgery and the European Society of
      Cataract and Refractive Surgeons. Preoperative data about visual acuity, patient
      signs and symptoms, and complications requiring IOL removal were assessed.
      Postoperative results and outcomes were also analyzed. Complications and symptoms
      for each of the following major groups of foldable IOLs explanted were tabulated
      separately: 3-piece hydrophilic acrylic or hydrogel; 3-piece monofocal silicone;
      3-piece hydrophobic acrylic; 1-piece hydrophobic acrylic with haptics; 3-piece
      multifocal silicone; 1-piece plate-type silicone. A total of 286 surveys were
      returned for evaluation. Intraocular lens calcification, incorrect lens power,
      optical visual aberrations, and decentration/dislocation were the most common
      reasons for removing a foldable IOL. Accurate IOL measurements, meticulous
      surgical technique, proper patient counseling, and careful manufacture of
      foldable IOL materials are the most important factors in avoiding complications
      with foldable IOLs.

PMID- 12498860
TI  - Resident cataract surgical training in United States residency programs.
AB  - A comprehensive survey was sent to the residency directors of 129 ophthalmology
      training programs in the United States. Forty percent of residents gained
      experience as primary surgeon during their first year; 43% performed only part of
      the surgery. Seventy-three percent began learning cataract extraction using the
      extracapsular cataract extraction (ECCE) technique, 24% began with
      phacoemulsification, and 2% began with either method. If beginning with ECCE, 18%
      must have completed more than 10 before moving to phacoemulsification, 37% more
      than 5, and 45% more than 1. Seventy-five percent learned various
      phacoemulsification techniques; 25% learned only 1 technique. If beginning with 1
      technique, 44% began with the scleral tunnel combined with divide and conquer.
      Sixty-four percent learned phacoemulsification on the Alcon Legacy, 21% on the
      Alcon Legacy and Storz Millennium, and 6% on the Storz Millennium. Sixty-eight
      percent of residents rotated out of their main facility to perform cataract
      surgery. The mean and median number of cataract procedures a resident completed
      by the end of training was 113 and 100, respectively.

PMID- 12498861
TI  - Progressive post-LASIK keratectasia: biomechanical instability or chronic disease
      process?
AB  - Progressive post-LASIK keratectasia (PPLK) is a progressive deformation of
      corneal anatomy that occurs rarely but may have severe consequences. Using the
      scientific literature and new hypotheses, we attempted to determine whether PPLK
      is a biomechanical result of laser in situ keratomileusis (LASIK), a chronic
      disease process affecting individuals predisposed to the condition, or a
      combination of processes. We look at whether the combination of fatigue,
      specifically a form of dynamic fatigue, and proteolysis provides an environment
      conducive to the occurrence and progression of PPLK. This review may raise more
      questions than it answers and in so doing may move us toward a better
      understanding of this occasionally serious consequence of LASIK.

PMID- 12498862
TI  - Bilateral spontaneous subluxation of scleral-fixated intraocular lenses.
AB  - Two young men with primary ectopic lenses had intracapsular cataract extraction
      and scleral fixation of posterior chamber intraocular lenses (PC IOLs) using 10-0
      polypropylene sutures tied to the IOL eyelets. Three to 9 years after
      implantation, spontaneous IOL vertical subluxation occurred in all 4 eyes (5 IOL
      loops), probably because of suture breakage. Late subluxation of a sutured IOL
      may occur several years after implantation. Double fixation and thicker sutures
      should be considered, especially in young patients.

PMID- 12498863
TI  - Malignant glaucoma induced by a phakic posterior chamber intraocular lens for
      myopia.
AB  - A 23-year-old woman with -14.00 diopters of myopia requested emmetropia for
      professional reasons. An ICM 130 V2 myopic phakic intraocular lens (IOL) (Staar
      Surgical AG) was implanted in the posterior chamber. Three days later, the
      patient developed malignant glaucoma. Pupillary block glaucoma and choroidal
      hemorrhage or effusion were ruled out. As maximum medical treatment failed, rapid
      secondary surgery was performed with sclerotomy, aspiration in the midvitreous
      cavity, and removal of the IOL. The follow-up was 43 months.

PMID- 12498864
TI  - Phakic posterior chamber intraocular lens pupillary block.
AB  - A 49-year-old woman developed bilateral pupillary block after implantation of a
      phakic posterior chamber intraocular lens despite patent-appearing but
      nonfunctional peripheral iridotomies. This case serves as a basis to identify
      clinical signs that distinguish this diagnosis from other causes of elevated
      intraocular pressure and types of pupillary block.

PMID- 12498865
TI  - Refractive changes produced by capsule contraction after piggyback acrylic
      intraocular lens implantation.
AB  - I describe a case of anterior capsule contraction after implantation of piggyback
      acrylic intraocular lenses (IOLs). Treatment by neodymium:YAG capsulotomy
      resulted in anterior chamber deepening despite a myopic shift. With acrylic IOLs,
      refractive changes may be due to optical deformation rather than axial shifts.

PMID- 12498866
TI  - Phacoemulsification with a blow-out fracture in the early postoperative period.
AB  - An 81-year-old woman had uneventful phacoemulsification through a self-sealing
      clear corneal wound. The postoperative course was complicated by a fall 10 days
      after surgery during which she hit her face on the carpet with sufficient force
      to cause an orbital floor blow-out fracture. Despite the blow, the corneal wound
      remained intact. As well as the advantage of rapid visual rehabilitation,
      sutureless corneal wounds provide a secure incision that has the ability to avoid
      leakage and iris prolapse despite great forces that may be applied to them.

PMID- 12498867
TI  - Intralenticular metallic foreign body.
AB  - We report the case of a 58-year-old man who despite having an intralenticular
      metallic foreign body maintained good vision for at least 40 years. We describe
      the natural course of intraocular foreign body and the healing capacity of the
      anterior lens capsule as well as management issues to consider when dealing with
      intraocular foreign bodies.

PMID- 12498868
TI  - Rhodococcus globerulus keratitis after laser in situ keratomileusis.
AB  - A healthy 20-year-old woman with myopia had uneventful bilateral laser in situ
      keratomileusis after which the uncorrected visual acuity was 20/20 in the right
      eye and 20/30 in the left eye. Fifteen days later, a stromal paraxial lesion was
      found in the right eye with a corresponding loss of visual acuity, pain, and
      photophobia. The flap was lifted and the infiltrate scraped for smears. Cultures
      showed that Rhodococcus globerulus was the infectious agent. Intensive topical
      antibiotic treatment was applied with good visual results.

PMID- 12498869
TI  - Unidentified foreign objects in the wound after clear corneal tunnel
      phacoemulsification.
AB  - We describe the presence of unidentified foreign objects, including small
      freckles and fibrillary material, in the corneal stroma seen on slitlamp
      biomicroscopy in 2 patients who had uneventful clear corneal tunnel
      phacoemulsification. Clinically, these foreign objects did not appear to affect
      the final visual outcome. Further study is required to explain their source, role
      in the wound healing, and toxicity and the behavior of metallic particles in the
      magnetic field in relation to magnetic resonance imaging.

PMID- 12498870
TI  - Keratic precipitates and iris nodules after uneventful phacoemulsification in
      diabetic patients.

PMID- 12498871
TI  - Capsular tension ring in eyes with pseudoexfoliation.

PMID- 12498872
TI  - Effect of ablation zone decentration on optical aberrations.

PMID- 12498873
TI  - Evolution of cataract surgery anesthesia.

PMID- 12498874
TI  - Basilea pharmaceutica AG mining a rich inheritance.

PMID- 12498875
TI  - One, two, infinity: genomes filled with aptamers.

PMID- 12498876
TI  - Augmenting vitamin D to combat genetic disease.
AB  - Vitamin D-resistant rickets is a genetic disease that causes severe bone
      underdevelopment due to mutations in the vitamin D receptor. Orthogonal analogs
      of vitamin D were recently identified that correct defects in the ligand binding
      pocket of a mutant receptor associated with this disease.

PMID- 12498877
TI  - Control in the N-linked glycoprotein biosynthesis pathway.
AB  - N-linked glycosylation is vital for the development and maintenance of eukaryotic
      cells. The individual steps of this complex process are slowly being elucidated.
      In this issue, the Imperiali group further dissects the mechanics of
      oligosaccharyl transferase using substrate analogs.

PMID- 12498878
TI  - Combinatorial glycosylation of glycopeptide antibiotics.
AB  - The glycosyltransferases GtfE and GtfD from the vancomycin producer Amycolatopsis
      orientalis have promiscuous substrate and NDP-sugar specificities. They have been
      used to generate novel glycopeptide antibiotics containing the heptapeptide
      scaffolds of vancomycin and teichoplanin.

PMID- 12498879
TI  - One step closer to a sweet conclusion.
AB  - OtsA is required for the biosynthesis of trehalose, a nonreducing disaccharide
      that is important for bacterial survival and stress responses. In this issue of
      Chemistry & Biology, the structure of OtsA is uncovered and reveals an unexpected
      relationship between the enzyme's structure and function.

PMID- 12498880
TI  - Small molecules, big impact: a history of chemical inhibitors and the
      cytoskeleton.
AB  - Chemical inhibitors, whether natural products or synthetic, have had an enormous
      impact on the study of the eukaryotic cytoskeleton. Here we review the history of
      some of the most widely used cytoskeletal poisons and their influence on our
      understanding of cytoskeletal functions. We then highlight several new inhibitors
      and the targeted screens used to identify them and discuss why this approach has
      been successful.

PMID- 12498881
TI  - Remarkable structural similarities between diverse glycosyltransferases.
AB  - From a functional standpoint, glycosyltransferases (GTases) comprise one the most
      diverse group of enzymes in existence. Every category of biopolymer
      (oligosaccharides, proteins, nucleic acids, and lipids) plus numerous natural
      products are modified by GTases, with remarkably varied effects. Given the
      structural and functional diversity of the products of glycosyl transfer combined
      with the often distant evolutionary relationships between glycosyltransferases,
      it is not surprising that sequence homologies between glycosyltransferases are
      low. What is surprising is that the majority of glycosyltransferases belong to
      only two structural superfamilies, implying that nature has come up with only a
      few solutions to the ubiquitous problem of how to catalyze glycosyl transfer. The
      conservation of GTase structure suggests that it will be simpler to manipulate
      glycosyltransferases for various applications than previously envisioned. A new
      age in glycoconjugate chemistry is beginning.

PMID- 12498882
TI  - Trapping distinct structural states of a protein/DNA interaction through
      disulfide crosslinking.
AB  - The N-terminal domain of the Escherichia coli Ada protein (N-Ada) repairs methyl
      phosphotriesters in DNA through a zinc-mediated transfer to Cys38 of the protein.
      Methylation of Cys38 enhances the sequence-specific DNA affinity of N-Ada by
      approximately 1000-fold, thereby enabling the protein to activate the genes of a
      methylation-resistance regulon. It is of interest to understand the structural
      basis for metalloactivated methyl transfer and methylation-dependent enhancement
      of DNA binding activity. Although recent progress has been made on the structural
      front, efforts to develop a complete picture of N-Ada structure/function have
      been hampered by the inability to prepare homogeneous protein/DNA complexes
      representing different states of the unmethylated protein. Here, we describe the
      development of an approach to trap both sequence-specific and nonsequence
      specific DNA recognition complexes of N-Ada through formation of an
      intermolecular disulfide crosslink between the protein and DNA.

PMID- 12498883
TI  - Incorporation of glucose analogs by GtfE and GtfD from the vancomycin
      biosynthetic pathway to generate variant glycopeptides.
AB  - Analogs of the glycopeptide antibiotics vancomycin and teicoplanin with
      alterations in one or both sugar moieties of the disaccharide have been prepared
      by tandem action of the vancomycin pathway glycosyltransferases GtfE and GtfD.
      All four regioisomers (2-, 3-, 4-, 6-) of TDP-deoxyglucoses and UDP/TDP
      aminoglucoses were prepared, predominantly by action of D-glucopyranosyl-1
      phosphate thymidylyltransferase, E(p). GtfE transferred the deoxyglucoses or
      aminoglucoses onto the 4-OH of 4-hydroxyphenylglycine of both the vancomycin and
      teicoplanin aglycone scaffolds. Kinetic analysis indicated the 2-, 3-, 4-, and 6
      amino-glucoses were transferred by GtfE with only a 4- to 30-fold drop in k(cat)
      and no effect on K(m) compared to the native substrate, UDP/TDP-glucose,
      suggesting preparative utility. The next enzyme, GtfD, could utilize the variant
      glucosyl-peptides as substrates for transfer of L-4-epi-vancosamine. The
      aminosugar moieties in these variant glycopeptides introduce sites for acylation
      or reductive alkylation.

PMID- 12498884
TI  - Sequence-dependent DNA dynamics by scanning force microscopy time-resolved
      imaging.
AB  - Scanning force microscopy was used to study in fluid the conformational
      fluctuations of two double-stranded DNA molecules resulting from differently cut
      pBR322 circular DNAs. A new approach was conceived to monitor the thermodynamic
      equilibrium of the chain dynamics on different scale lengths. This method made it
      possible to demonstrate that both the observed DNA molecules were allowed to
      equilibrate only on their local small-scale dynamics during the time of the
      experiment. This capability of monitoring the length scale and the time scale of
      the equilibration processes in the dynamics of a DNA chain is relevant to give an
      insight in the thermodynamics of the DNA binding with proteins and synthetic
      ligands. It was also shown that the small-scale equilibration of the DNA chain
      during surface-restricted dynamics is enough to allow a valid measurement of the
      local sequence-dependent curvature.

PMID- 12498885
TI  - Neoglycopeptides as inhibitors of oligosaccharyl transferase: insight into
      negotiating product inhibition.
AB  - Linear hexapeptides featuring the asparagine mimetics alanine-beta-hydrazide,
      alanine-beta-hydroxylamine, and 1,3-diaminobutanoic acid have been synthesized as
      oligosaccharyl transferase (OT) substrate mimetics and chemoselectively N
      glycosylated to obtain the corresponding neoglycopeptides as OT product mimetics.
      The effect of glycosylation on the binding of these asparagine surrogates is in
      stark contrast with the effect of modification of native asparagine. In native N
      linked glycosylation, product inhibition is minimal and glycopeptides show very
      low affinity for OT. In contrast, glycosylation of the substrate mimetics
      maintains or even improves affinity of the corresponding product mimetic for OT.
      Conformational considerations suggest that the flexibility of the N-glycosyl
      linkage in these neoglycopeptides allows them to be accommodated in the OT
      binding site while the native trans glycosyl amide linkage is rejected. These
      results provide insight into how OT minimizes product inhibition, thereby
      ensuring effective substrate turnover.

PMID- 12498886
TI  - Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on
      a single cysteine residue.
AB  - S-Nitrosylation of specific cysteine residues is a reversible signaling mechanism
      of nitric oxide (NO) generated by NO synthase (NOS) enzymes. In some proteins,
      evidence has accumulated that more than one cysteine can be S-nitrosylated;
      however, it is difficult to distinguish S-nitrosylation on separate cysteine
      residues. We report a novel simple, sensitive, and specific procedure for
      nitrosopeptide mapping. Dexras1 is a monomeric G protein whose guanine nucleotide
      exchange activity is augmented by NO; the identity and number of its S
      nitrosylated cysteines is unknown. We describe the radiolabeling of S
      nitrosylated cysteine residues in Dexras1. A nitrosopeptide map, generated by two
      dimensional peptide chromatography, reveals that only a single cysteine is S
      nitrosylated following NO exposure. Mutagenesis of Cys11 abolished the effect of
      NO donors on Dexras1, implicating this residue in the NO-mediated activation of
      Dexras1.

PMID- 12498887
TI  - Insights into trehalose synthesis provided by the structure of the retaining
      glucosyltransferase OtsA.
AB  - Trehalose is a nonreducing disaccharide that plays a major role in many
      organisms, most notably in survival and stress responses. In Mycobacterium
      tuberculosis, it plays a central role as the carbohydrate core of numerous
      immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The
      classical pathway for trehalose synthesis involves the condensation of UDP
      glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the
      retaining glycosyltransferase OtsA. The configurations of two anomeric positions
      are set simultaneously, resulting in the formation of a double glycoside. The
      three-dimensional structure of the Escherichia coli OtsA, in complex with both
      UDP and glucose-6-phosphate, reveals the active site at the interface of two
      beta/alpha/beta domains. The overall structure and the intimate details of the
      catalytic machinery reveal a striking similarity to glycogen phosphorylase,
      indicating a strong evolutionary link and suggesting a common catalytic
      mechanism.

PMID- 12498888
TI  - Spatially discrete, light-driven protein expression.
AB  - Transgene-based inducible expression systems offer the potential to study the
      influence of any gene at any point during an organism's lifetime. However, the
      expression of individual genes is both temporally and spatially (i.e.,
      cell/tissue)-regulated. The inducible gene expression systems devised to date do
      not offer fine spatial control over gene expression. We describe herein the
      creation and study of a light-activatable, ecdysone-inducible gene expression
      system. We have constructed the first example of a caged ecdysteroid, which is
      virtually inactive as an inducing agent in a luciferase-based gene expression
      system. However, upon exposure to brief illumination, the caged ecdysteroid is
      rapidly converted into active beta-ecdysone. Caged beta-ecdysone is cell
      permeable, can be intracellularly photouncaged, and, in combination with spot
      illumination, can be used to drive spatially discrete protein expression in a
      multicellular setting.

PMID- 12498889
TI  - The albonoursin gene Cluster of S noursei biosynthesis of diketopiperazine
      metabolites independent of nonribosomal peptide synthetases.
AB  - Albonoursin [cyclo(deltaPhe-DeltaLeu)], an antibacterial peptide produced by
      Streptomyces noursei, is one of the simplest representatives of the large
      diketopiperazine (DKP) family. Formation of alpha,beta unsaturations was
      previously shown to occur on cyclo(L-Phe-L-Leu), catalyzed by the cyclic
      dipeptide oxidase (CDO). We used CDO peptide sequence information to isolate a
      3.8 kb S. noursei DNA fragment that directs albonoursin biosynthesis in
      Streptomyces lividans. This fragment encompasses four complete genes: albA and
      albB, necessary for CDO activity; albC, sufficient for cyclic dipeptide precursor
      formation, although displaying no similarity to non ribosomal peptide synthetase
      (NRPS) genes; and albD, encoding a putative membrane protein. This first isolated
      DKP biosynthetic gene cluster should help to elucidate the mechanism of DKP
      formation, totally independent of NRPS, and to characterize novel DKP
      biosynthetic pathways that could be engineered to increase the molecular
      diversity of DKP derivatives.

PMID- 12498890
TI  - Photo-polymerization shrinkage-stress kinetics in resin-composites: methods
      development.
AB  - OBJECTIVES: Studies of free shrinkage-strain kinetics on restoratives have begun
      to multiply. However, there have been fewer investigations of the more difficult
      problem of concurrent stress-kinetic measurements. The aim was to outline design
      parameters for a new methodology for this problem, amenable especially to light
      cured materials, and to present illustrative results for a range of restorative
      composites. METHODS: Absolute values of stress measurable for a given material
      and geometry are dependent upon the stiffness of the measurement system. In an
      infinitely stiff system, the measured stress would also tend towards infinity.
      Real teeth and their cavities are not infinitely stiff; they have elastic and
      visco-elastic compliance. Consequently, it is important that some minimal, but
      essentially constant compliance be allowed, whatever the final or time-dependent
      modulus of the material may be. This goal has been realised by measurement of the
      time-development, for a disk-geometry specimen (phi=10, h approximately 1.0 mm)
      of stress (S(r)), with a calibrated cantilever beam-geometry load cell. A novel
      specimen-holder design was used for this purpose, held in a rigid base assembly.
      Specimen thicknesses (or gap-widths) of 0.8 and 1.2 mm were specifically
      investigated on four representative resin-composites. Concurrent measurements
      were made of the end-displacement of the cantilever load cell, relative to a
      lower glass plate retaining the specimen. RESULTS: Load-calibration of the
      cantilever load cell gave an end-displacement per unit stress of circa 6
      microm/MPa. This compares with literature values for cuspal compliance or
      displacement of circa 20 microm. Re-normalisation of the stress-data was
      implemented. This was accomplished assuming Hooke's law behavior at each instant
      and equivalent to a stiffer system, with a correction (multiplier) factor of 4 on
      the raw-stress values. For the materials examined, resultant maximum-stress
      levels determined were circa 5-8 MPa Stress-levels obtained at 1.2mm thickness
      were slightly higher (11-15%) than the level of stress obtained at 0.8 mm
      thickness. This is attributable to the greater mass of material undergoing
      shrinkage at 1.2 mm, offset slightly by the different C-factors. SIGNIFICANCE:
      The new device is a practical and self-contained system for rapid and accurate
      measurement of stress-kinetics in photo-polymerising and also self-cure
      materials.

PMID- 12498891
TI  - Effects of various finishing systems on the surface roughness and staining
      susceptibility of packable composite resins.
AB  - OBJECTIVES: The purpose of the present study was to investigate the influence of
      various finishing systems on the surface roughness and staining of three packable
      resin composites and a conventional microhybrid one. METHODS: Three packable
      composites (Solitaire-Heraeus-Kulzer, ALERT-Jeneric-Pentron, SureFil-Dentsply)
      and a conventional microhybrid (Z250-3M-ESPE) were used. Composite specimens were
      prepared and polished with Poli I and Poli II aluminum oxide pastes, Ultralap
      diamond paste, Enhance finishing points, Politip rubber polishers, fine and extra
      fine diamond burs, and 30-blade tungsten carbide burs according to the
      manufacturers' instructions. The polished surfaces were evaluated with a
      profilometer, and then immersed in 2% methylene blue for 24h. Afterwards, the
      specimens were prepared for the spectrophotometric analysis. Results were
      statistically analyzed by ANOVA and Tukey test. RESULTS: Significant differences
      were found for the surface roughness and staining recorded, with interaction
      among composite resins and the finishing systems used. No correlation was found
      between surface roughness and staining susceptibility (p=0.5657). SIGNIFICANCE:
      For most of the polishing agents used, Z250 presented the smoothest surfaces and
      the least dye uptake. ALERT presented the roughest surfaces, and Solitaire, the
      highest dye concentration. The smoothest surfaces were not necessarily the most
      stain resistant. Staining is highly influenced by each composite monomer and
      filler composition.

PMID- 12498892
TI  - A new method for the computer-aided evaluation of three-dimensional changes in
      gypsum materials.
AB  - OBJECTIVES: The quantitative evaluation of the time- or process-dependent three
      dimensional stability of dental materials is a common question in dentistry. An
      investigation procedure has been developed based on a CAD-surface model of a
      prepared upper canine, as well as a high-precision physical copy (metal master
      die). The specific aim of this study was to test this method's reliability.
      Additionally, the ability of the developed procedure to determine the three
      dimensional stability of resin-reinforced gypsum master casts over time was
      investigated. METHODS: Ten duplicate dies of improved dental stone (esthetic
      rock, dentona, Germany) were manufactured, and digitized 1, 3, 7, 28 and 56 days
      after pouring. A three-coordinate optical measuring device was used for the data
      acquisition. The three-dimensional accuracy of stone dies was determined by
      comparing the digitized data of the stone dies made from the metal master die to
      its CAD-surface model (Surfacer) Version 9.0. Imageware Inc., Ann Arbor Michigan,
      USA). To assess the procedure, test surfaces were created from the digitized data
      and compared with a reference. RESULTS: The mean deviation between the digitized
      point cloud and the test surface was less than 3 microm. During the 56 day
      examination period no significant three-dimensional changes in dimensional
      stability were found. SIGNIFICANCE: The procedure for the quantitative three
      dimensional evaluation was shown to be suitable. Best-fit registration enabled a
      reliable alignment of the point cloud to the CAD-surface model. Alteration of
      three-dimensional accuracy over 6 weeks was insignificant and without clinical
      relevance.

PMID- 12498893
TI  - In vitro biological response to core and flowable dental restorative materials.
AB  - OBJECTIVES: In vitro cytotoxicities of commercially available core and flowable
      dental restorative materials were assessed and compared to traditional resin
      composites. Our hypothesis was that the increased resin diluents added to achieve
      higher flow in flowables would increase cytotoxicities, whereas the higher filler
      content of core materials would decrease cytotoxicities relative to traditional
      resin composites. METHODS: Specimens were made under aseptic conditions, then
      extracted into an artificial saliva solution for 0-4 weeks, to assess the effect
      of aging on cytotoxicity. After extraction, specimens were tested for
      cytotoxicity in vitro using Balb/c fibroblasts in direct contact format. Cells
      were exposed to the materials for 48h, after which the mitochondrial activity of
      the cells was measured (MTT method). Cellular activity was normalized to Teflon
      negative controls. RESULTS: Core materials were uniformly and severely (<50% of
      Teflon cellular activity) cytotoxic initially, but several materials (Corepaste,
      Definite core) improved somewhat with aging in artificial saliva. Flowable
      materials were uniformly and severely cytotoxic with no trend toward improvement
      with aging. The Definite-flow was the least cytotoxic of the flowable materials,
      but it too was severely cytotoxic. SIGNIFICANCE: Commercially available core and
      flowable restorative materials showed severe in vitro cytotoxicities that are
      worse than some traditional composites and most dental casting alloys and
      amalgams used today. Of particular note was the persistent cytotoxicity of these
      materials after 4 weeks of extraction with artificial saliva. These
      cytotoxicities indicate a continuing release of mass from these materials at
      levels that have biological relevance in vitro. In vivo relevance of these
      cytotoxicities is less clear, but these results indicate a higher biological risk
      for these materials compared to traditional materials that exhibit less initial
      toxicity and improve with aging time.

PMID- 12498894
TI  - The recharge of esthetic dental restorative materials with fluoride in vitro-two
      years' results.
AB  - OBJECTIVES: A range of esthetic restorative dental materials are now available to
      dental clinicians. The aim of this study was to evaluate the relative fluoride
      recharge potential of a number of these materials in vitro over two years.
      METHODS: Disc samples (12 mm x 2 mm) of each of the materials were placed into
      artificial saliva at neutral pH. The materials tested were: two glass ionomers
      (Chemfil; Ketac-Fil), two resin-modified glass ionomers (Photac-Fil Aplicap;
      Vitremer), two compomers (Dyract; Compoglass) and two composites (Heliomolar;
      Concise). At 13 intervals over a two years period the discs were subjected to a 2
      min fluoride recharge by exposure to sodium fluoride (500 ppm F). The pre- and
      post-recharge fluoride release values were determined using an ion sensitive
      electrode. RESULTS: At all time intervals the post-recharge fluoride release of
      the materials was significantly different (MANOVA p<0.0001). The mean values for
      post-recharge fluoride release after two years were: Chemfil 10.3, Ketac 3.0,
      Vitremer 9.0, Photac-Fil Aplicap 12.1, Compoglass 5.0, Dyract 3.6, Concise 0.3,
      Heliomolar 0.2 (units = microgF/cm(2)/h). SIGNIFICANCE: Esthetic fillings vary
      significantly in their capacity to absorb and re-release fluoride. The glass
      ionomer-based materials displayed a far greater potential for fluoride recharge
      than the composites, in which the recharge was virtually negligible. Whilst it
      cannot be assumed that fluoride release is directly proportional to cariostatic
      potential, these results suggest that, where possible, glass ionomer-based
      materials should be used in patients who have a high caries rate.

PMID- 12498895
TI  - Mercury release from dental amalgams into continuously replenished liquids.
AB  - OBJECTIVE: Studies have been performed using high- and low-copper amalgams to
      measure the amounts of mercury dissolution from dental amalgam in liquids such as
      artificial saliva; however, in most cases, mercury dissolution has been measured
      under static conditions and as such, may be self-limiting. This study measured
      the mercury release from low- and high-copper amalgams into flowing aqueous
      solutions to determine whether the total amounts of dissolution vary under these
      conditions when tested at neutral and acidic pH. METHODS: High- and low-copper
      amalgam specimens were prepared and kept for 3 days. They were then
      longitudinally suspended in dissolution cells with an outlet at the bottom.
      Deionized water or acidic solution (pH1) was pumped through the cell. Test
      solutions were collected at several time periods up to 6 days or 1 month and then
      analyzed with a cold vapor atomic absorption spectrophotometer. After dissolution
      testing, the specimens were examined using SEM/XEDA for any selective degradation
      of the phases in the amalgam. RESULTS: Except for the high-copper amalgam in the
      pH1 solution, the dissolution rates were found to decrease exponentially with
      time. The rate for the high-copper amalgam in pH1 solution slowly increased for 1
      month. The total amounts (microgram/cm(2)) of mercury released over 6 days or 1
      month from both types of amalgam in deionized water were not significantly
      different (p>/=0.05). The high-copper amalgam released significantly more mercury
      than the low-copper amalgam in the pH1 solution at both time periods. For both
      amalgams, the dissolution in pH1 was significantly higher than in deionized
      water. SIGNIFICANCE: Mercury dissolution from amalgam under dynamic conditions is
      enhanced in an acidic media, and most prominently for a high-copper formulation.

PMID- 12498896
TI  - Extended creep behavior of dental composites using time-temperature superposition
      principle.
AB  - OBJECTIVES: The purpose of the study was to characterize long-term creep
      deformation behavior of selected dental composite resins. METHODS: Two hybrid
      composite resins (one midifill type Clearfill and the other minifill type
      Charisma) and one microfill type (Durafill) were evaluated. 25 mm x 10 mm x 2 mm
      rectangular bar specimens were subjected to single cantilever mode of flexural
      loading and their creep compliance changes determined over 10 min durations in
      the temperature range of 32-120 degrees C at 5 degrees C intervals. The reference
      temperature selected was the body temperature of 37 degrees C for the oral
      environment. All creep compliance curves at other temperatures were shifted along
      the log time axis to superimpose them on the reference temperature (37 degrees C)
      curve to generate an extended isothermal master curve over eight decades of time
      (seconds). The shift factors were determined as a function of temperature and
      fitted by the least square method to the William-Landel-Ferry model. RESULTS: The
      data showed excellent fit to the model, indicating the validity of the model to
      characterize the long-term behavior using the time-temperature superposition
      principle. The creep compliance changed from initial mean values of 76, 245 and
      605 microm(2)/N to 3 year mean values of 217, 880 and 1653 microm(2)/N for
      Clearfill, Charisma and Durafill systems, respectively. These means were
      significantly different both as a function of composites and time (p<0.05).
      SIGNIFICANCE: The results indicate that resin volume fraction and filler
      parameters may play a critical role in the long-term deformation and energy
      release processes, and these processes may be an important influence on the long
      term clinical durability of composite restorations.

PMID- 12498897
TI  - Galvanic corrosion behavior of implant suprastructure dental alloys.
AB  - OBJECTIVE: The purpose of this study was to evaluate and compare in vitro, the
      galvanic corrosion behavior of Co-Cr alloys (R2000, R800), Ni-Cr (RCS), silver
      palladium (Jelstar), Gold (Pontallor-4) and Ternary Ti (experimental Ter Ti) when
      coupled with endosseous Ti implant abutment material. Amalgam alloy and
      commercially pure Ti cylinders (SSTi) were coupled with endosseous Ti implants as
      negative and positive controls, respectively. METHODS: An EG&G Model 263 Scanning
      Potentiostat was used for this purpose. Specimens were prepared and fresh
      artificial saliva was used as an electrolyte solution. The experiment run time
      was 24h for each couple. The common potential, galvanic current and current
      integration during the last 6h were recorded for each couple. RESULTS: The
      results showed that the best couples were Ti/Pontallor-4, Ti/Ter Ti, Ti/R800 and
      Ti/Jelstar. The least acceptable couples were Ti/amalgam, SSTi/SSTi and Ti/R2000,
      while the Ti/RCS couple showed unstable galvanic corrosion behavior.
      SIGNIFICANCE: It is concluded that the following alloys can be used as
      suprastructure alloys with Ti implants: Pontallor-4, R800, Jelstar and Ter Ti.
      Although Ter Ti alloy is an experimental alloy, it showed good results, but
      cannot be used in the clinical field unless extensive investigations are carried
      out. The SSTi/SSTi couple showed unexpected galvanic corrosion behavior which
      needs further investigation.

PMID- 12498898
TI  - Submicron hiati in acid-etched dentin are artifacts of desiccation.
AB  - OBJECTIVES: The submicron hiatus represents a potential space between the base of
      the collagen network and the mineralized dentin when dentin is acid-etched for
      bonding. These spaces were observed in SEM studies after acid-etched dentin
      specimens were critical point dried or dehydrated in hexamethyldisilasane.
      However, they have never been identified in TEM studies of dentin hybrid layers.
      This study critically examined the cause of submicron hiati formation using a
      silver staining technique to measure nanoleakage. METHODS: Two multi-step, total
      etch adhesives (One-Step, Bisco; Single Bond, 3M) and two single-step, self
      etching adhesives (Prompt L-Pop, ESPE; One-Up Bond F, Tokuyama) were examined.
      Flat dentin surfaces were bonded with these adhesives and a lining composite. In
      each adhesive group, 0.8mm thick slabs from the same bonded tooth were coated
      with nail varnish applied 1mm from the bonded interfaces. The varnish was either
      left to dry completely for 10min before immersing in 50wt% silver nitrate
      (AgNO(3)) for 24h (group D), or painted on blotted tooth slabs that were
      immediately dropped into the AgNO(3) solution (group M). After developing,
      undemineralized, unstained, epoxy resin-embedded sections were prepared for
      transmission electron microscopy (TEM) to identify the amount and distribution of
      silver uptake. RESULTS: Nanoleakage patterns were observed in all adhesive-bonded
      teeth, regardless of brand. Fine reticular silver deposits were also found in the
      underlying undemineralized dentin. In group D, submicron hiati were seen as
      tunnels of heavy silver deposits beneath hybrid layers. Specifically, a hiatus
      occurred between the undemineralized intertubular dentin and a cohesively
      fractured layer of the same matrix that was attached to the base of the hybrid
      layer. Hiati were completely absent in group M, regardless of the brand of
      adhesive. SIGNIFICANCE: Submicron hiati are artifacts created by desiccation
      during specimen processing, and should be referred to as such in future studies
      of bonded dentin interfaces.

PMID- 12498899
TI  - The effect of cement type and mixing on the bi-axial fracture strength of
      cemented aluminous core porcelain discs.
AB  - OBJECTIVES: Luting agents in current use include zinc phosphate, zinc
      polycarboxylate, conventional glass-ionomer, resin-modified glass-ionomer and
      resin composite cements. Dental cements may be used in practice with a wide range
      of mixing ratios. Accordingly, the impact of cement type and mixing on the
      strength of alumina reinforcing porcelain was investigated. METHODS: Standard
      Vitadur-N core porcelain disc specimens were coated with different cement types
      of varying mixing ratios to produce a luting thickness. Sets of 25 coated
      specimens were stored at 37+/-1 degrees C for 24h prior to testing. Mean fracture
      strengths, standard deviations and associated Weibull Moduli (m) were determined
      using bi-axial fracture (ball-on-ring). RESULTS: The strength data for porcelain
      discs coated with different cement types manipulated at the consistency indicated
      for luting all-ceramic crowns showed little variation in magnitude and
      consistency. The plots of survival probability against strength for specimens
      coated with acid-base cements appear to develop a slight asymmetry at the lower
      values of strength. This effect was more pronounced for acid-base cements
      prepared at mixing ratios below that recommended for luting purposes.
      SIGNIFICANCE: The corrosive acidic environment of acid-base cements may have
      extended pre-existing flaws in the porcelain discs producing the asymmetry in the
      survival distributions. Resin composite cements appear to enhance the strength of
      the porcelain disc specimens possibly by healing the surface imperfections. This
      may increase their scope of application over acid-base cements to include the
      luting of all-ceramic restorations.

PMID- 12498901
TI  - Bradykinin B1 and B2 receptors differentially regulate cardiac Na+-H+ exchanger,
      Na+-Ca2+ exchanger and Na+-HCO3- symporter.
AB  - Bradykinin B(1) and B(2) receptors are up-regulated in the infarcted myocardium,
      and both receptors are involved in the regulation of intracellular pH and Ca(2+).
      The present study investigated the role of bradykinin B(1) and B(2) receptors in
      the regulation of Na(+)-H(+) exchanger (NHE-1), Na(+)-Ca(2+) exchanger (NCE-1)
      and Na(+)-HCO(3)(-) symporter (NBC-1) in the infarcted myocardium. NHE-1, NCE-1
      and NBC-1 mRNA expression was determined by Northern blot analysis and the
      protein levels by Western blot analysis. Measurements were performed 1, 7 and 14
      days after induction of myocardial infarction. Localization of NHE-1, NCE-1 and
      NBC-1 within the myocardium was studied using confocal microscopy. Cardiac
      morphology was measured in picrosiris-red-stained hearts. Rats were treated with
      placebo, the bradykinin B(2) receptor antagonist icatibant (0.5 mg/kg/day) or the
      bradykinin B(1) receptor antagonist des-Arg(9)-[Leu(8)]bradykinin (1 mg/kg/day).
      Treatment was started 1 week prior to surgery and continued until 1, 7 and 14
      days post infarction. NHE-1, NCE-1 and NBC-1 mRNA expression and protein levels
      were increased 1 day and reached maximum values on day 7 post infarction. NHE-1
      was localized in the plasma membrane, NCE-1 in the membrane of the sarcoplasmatic
      reticulum and NBC-1 near the Z-line. Icatibant reduced NHE-1 and inhibited NCE-1
      mRNA- and protein up-regulation, while des-Arg(9)-[Leu(8)]bradykinin had no
      effect on NHE-1 and NCE-1 expression and translation. Transcriptional and
      translational up-regulation of NBC-1 was unaffected by the bradykinin B(1) and
      B(2) receptor antagonists. Icatibant, but not des-Arg(9)-[Leu(8)]bradykinin,
      limited infarct size and reduced left ventricular dilation, septal thickening and
      interstitial fibrosis post infarction. Bradykinin B(2) receptors are involved in
      transcriptional and translational regulation of NHE-1 and NCE-1 in the ischemic
      myocardium. Chronic B(2) receptor blockade might exert an anti-ischemic effect
      via limitation of NHE-1-mediated acidosis and NCE-1-mediated Ca(2+)-overload.

PMID- 12498902
TI  - Involvement of the system L amino acid transporter on uptake of S-nitroso-L
      cysteine, an endogenous S-nitrosothiol, in PC12 cells.
AB  - Previously, we proposed that S-nitroso-L-cysteine, an endogenous S-nitrosothiol,
      was incorporated via the system L-like amino acid transporter(s) in rat brain
      slices. In this study, we investigated the effect of S-nitroso-L-cysteine on L
      [3H]leucine uptake in PC12 cells (a neuronal cell line). L-[3H]Leucine uptake in
      PC12 cells was Na(+) independent and significantly inhibited by an inhibitor of
      system L and by L-phenylalanine, L-cysteine, L-methionine and L-leucine at 1 mM.
      The effects of L-alanine, L-serine and L-threonine were limited. S-Nitroso-L
      cysteine, but not other nitric oxide compounds, inhibited L-[3H]leucine uptake,
      and this inhibitory effect was eliminated by washing with buffer. System L is
      composed of the 4F2 light chains (LAT1 or LAT2) and the heavy chain, and the
      transcripts of these components were detected in RNA from PC12 cells. These
      findings suggest that S-nitroso-L-cysteine is incorporated via the system L amino
      acid transporter and thus regulates cell responses in PC12 cells.

PMID- 12498903
TI  - Interactions of the narcotic l-alpha-acetylmethadol with human cardiac K+
      channels.
AB  - l-alpha-acetylmethadol is a long-acting narcotic analgesic that is used in the
      treatment of opiate addiction. However, the drug has been associated with cases
      of QT interval prolongation and ventricular arrhythmia. To understand the
      mechanism underlying these clinical findings, we examined the effects of l-alpha
      acetylmethadol on the cloned human cardiac K(+) channels HERG (human ether-a-go
      go-related gene), KvLQT1/minK and Kv4.3. Using patch clamp electrophysiology, we
      found that l-alpha-acetylmethadol inhibited HERG channel currents in a voltage
      dependent manner displaying an IC(50) value of 3 microM. The major active
      metabolite of l-alpha-acetylmethadol, noracetylmethadol, inhibited HERG with an
      estimated IC(50) values of 12 microM. l-alpha-acetylmethadol had little or no
      effect on Kv4.3 or KvLQT1/minK K(+) channel currents at concentration up to 10
      microM. We conclude that the proarrhythmic effects of l-alpha-acetylmethadol are
      due to specific blockade of the HERG cardiac K(+) channel and that its active
      metabolite noracetylmethadol may provide a safer alternative in the treatment of
      opiate addiction.

PMID- 12498904
TI  - Ceramide-induced alterations in dopamine transporter function.
AB  - The purpose of this study was to determine the effects of ceramide on dopamine
      and serotonin (5-HT, 5-hydroxytryptamine) transporters. Exposure of rat striatal
      synaptosomes to C2-ceramide caused a reversible, concentration-dependent decrease
      in plasmalemmal dopamine uptake. In contrast, ceramide exposure increased
      striatal 5-HT synaptosomal uptake. This increase did not appear to be due to an
      increased uptake by the 5-HT transporter. Rather, the increase appeared to result
      from an increase in 5-HT transport through the dopamine transporter, an assertion
      evidenced by findings that this increase: (1) does not occur in hippocampal
      synaptosomes (i.e., a preparation largely devoid of dopamine transporters), (2)
      occurs in striatal synaptosomes prepared from para-chloroamphetamine-treated rats
      (i.e., a preparation lacking 5-HT transporters), (3) is attenuated by
      pretreatment with methylphenidate (i.e., a relatively selective dopamine reuptake
      inhibitor) and (4) is inhibited by exposure to exogenous dopamine (i.e., which
      presumably competes for uptake with 5-HT). Taken together, these results reveal
      that ceramide is a novel modulator of monoamine transporter function, and may
      alter the affinity of dopamine transporters for its primary substrate.

PMID- 12498905
TI  - Block of erg current by linoleoylamide, a sleep-inducing agent, in pituitary GH3
      cells.
AB  - Linoleoylamide is physiological constituent of neurons. The effects of this
      agent, also a sleep-inducing agent, on ion currents in pituitary GH(3) cells were
      investigated. Hyperpolarization-elicited K(+) currents in GH(3) cells bathed in a
      high-K(+), Ca(2+)-free solution were studied to determine the effects of
      linoleoylamide and other related compounds on the I(K(IR)) that was sensitive to
      inhibition by E-4031 and identified as an erg (ether-a-go-go-related-gene)
      current. Linoleoylamide suppressed the amplitude of I(K(IR)) in a concentration
      dependent manner with an IC(50) value of 5 microM. Oleamide (20 microM) inhibited
      the amplitude of I(K(IR)), while neither arachidonic acid (20 microM) nor 14,15
      epoxyeicosatrienoic acid (20 microM) had an effect on it. In GH(3) cells
      incubated with anandamide (20 microM) or arachidonic acid (20 microM), the
      linoleoylamide-induced inhibition of I(K(IR)) remained unaltered. In inside-out
      patches, arachidonic acid (20 microM) and 14,15-epoxyeicosatrienoic acid (20
      microM) stimulated large-conductance Ca(2+)-activated K(+) channels; however,
      linoleoylamide (20 microM) had little or no effect on them. Under current-clamp
      mode, linoleoylamide (20 microM) increased the firing rate. In IMR-32
      neuroblastoma cells, linoleoylamide also suppressed I(K(IR)). This study provides
      the evidence that linoleoylamide has a depressant effect on the erg current, and
      suggests that this effect may affect hormonal secretion.

PMID- 12498906
TI  - Evidence for a non-MDR1 component in digoxin secretion by human intestinal Caco-2
      epithelial layers.
AB  - Caco-2 epithelial layers were used as a model to re-evaluate the mechanism(s) by
      which intestinal digoxin absorption is limited by its active secretion back into
      the lumen. It is widely recognised that intestinal secretion of digoxin is
      mediated by the ATP-binding cassette (ABC) transporter Multidrug Resistance 1,
      MDR1. In MDR1-transfected Madin-Darby canine kidney, MDCKII, cell monolayers,
      digoxin secretion was reduced by the MDR1 inhibitor cyclosporin A, whereas no
      inhibition was seen in the presence of MK-571, 3-([(3-(2-[7-chloro-2
      quinolinyl]ethyl)phenyl]-[(3-dimethylamino-3-oxoprphyl)-thio)-methyl]-thio)
      propanoic acid, a Multidrug Related Protein (MRP) inhibitor. In contrast, digoxin
      secretion by Caco-2 epithelia was significantly inhibited by both cyclosporin A
      and MK-571, suggesting that an additional non-MDR1 component may contribute to
      this transport. Since digoxin secretion by MRP2-transfected MDCKII monolayers was
      increased by only 1.2-fold relative to controls, it is likely that the
      contribution of MRP2 to digoxin secretion by Caco-2 cells is negligible. An
      additional MK-571-sensitive secretory pathway for digoxin, together with MDR1, is
      likely to mediate digoxin secretion in Caco-2 epithelia.

PMID- 12498907
TI  - Modulation of spontaneous transient Ca2+-activated K+ channel currents by cADP
      ribose in vascular smooth muscle cells.
AB  - Transient local releases of Ca(2+) from the sarcoplasmic reticulum activate
      nearby Ca(2+)-activated K(+) channels to produce spontaneous transient outward
      current (STOC) in smooth muscle cells. We examined if cADP-ribose, an endogenous
      mediator of Ca(2+) release channels of the sarcoplasmic reticulum, could modify
      STOC activity. In freshly isolated rat tail arterial cells, cADP-ribose (5
      microM) increased STOC frequency significantly from 308+/-26.2 to 398.8+/-28.8
      per minute. The average current at a test potential of -20 mV was increased
      significantly from 47.8+/-0.7 to 101.1+/-0.7 pA in the presence of cADP-ribose.
      The cell permeant antagonist 8-bromo-cADP-ribose (50 microM) reduced
      significantly the STOC frequency to 52.5+/-7.5 per minute and the average current
      to 24.7+/-0.1 pA. The STOCs were inhibited significantly by ryanodine (1 microM)
      and charybodotoxin (150 nM). These findings suggest the presence of basal cADP
      ribose activity in resting vascular smooth muscle cells and that STOC activity is
      stimulated by cADP-ribose.

PMID- 12498908
TI  - Cellular distribution of vanilloid VR1 receptor immunoreactivity in the guinea
      pig myenteric plexus.
AB  - Recent investigations suggest that vanilloid receptor-1 (VR1) immunoreactivity
      occurs in the intestine. We have determined and quantified this immunoreactivity
      in the myenteric plexus with respect to cholinergic and neurofilament protein
      positive neurones. Guinea-pig and rat preparations were dual-labelled with
      specific antibodies raised in rabbit or goat against vanilloid receptor-1 and
      against other neurochemical markers. In the rat ileum, both vanilloid receptor
      antibodies were co-distributed, whereas in the guinea-pig ileum and colon,
      tertiary fibres were also detected with the goat antibody. In the guinea-pig, all
      vanilloid receptor-1-immunoreactive cell bodies were choline acetyltransferase
      immunopositive (100%) and showed some immunoreactivity to neurofilament proteins
      (NFP-200 kDa (79%) or triplet (10.8%)) or calretinin. Immunoreactive fibres in
      the secondary plexus co-localised with calcitonin gene-related peptide (CGRP) and
      with substance P, calretinin and synapsin I in the tertiary plexus.
      Subpopulations of cholinergic neurones including sensory, interneuronal and
      secretory neurones express vanilloid receptor-1. Co-localisation with substance P
      and calretinin in fibres suggests that vanilloid receptor-1 may be expressed by
      excitatory motor neurones. The association of vanilloid receptors with calcitonin
      gene-related peptide and synaptic protein in fibres implies a role for vanilloid
      receptors in neurotransmitter/neuropeptide release. Although it is likely that at
      least some of the vanilloid receptor-bearing fibres originate in immunopositive
      myenteric soma, the origin of all these fibres cannot be identified in the
      present study.

PMID- 12498909
TI  - Screening of novel pentacyclo-undecylamines for neuroprotective activity.
AB  - A novel series of pentacyclo-undecylamines with 8-benzylamino-8,11
      oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane (NGP1-01) as the lead compound
      was synthesised and screened for neuroprotective activity in the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian mouse model. We hypothesise
      that these compounds may attenuate excitotoxic neuronal cell death mediated
      through the NMDA receptor (similar to memantine), and through calcium channel
      block. The pentacyclo-undecylamines (300 mg/kg) were administered to C57BL/6 mice
      30 min before intraperitoneal (i.p.) MPTP administration (35 mg/kg). Striatal
      dopamine, 3,4-hydroxyphenylacetic acid (DOPAC), and homovanillic acid levels were
      analysed 10 days later by means of HPLC with electrochemical detection. Increased
      levels of DOPAC and homovanillic acid were observed when some of the test
      compounds were administered together with MPTP (compared to animals receiving
      only MPTP). One compound in the series, 8-phenylethylamino-8,11
      oxapentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane, attenuated MPTP-induced
      striatal dopamine depletion when compared to animals treated with MPTP only
      (p<0.05).

PMID- 12498910
TI  - Protective effects of selegiline and desmethylselegiline against N-methyl-D
      aspartate-induced rat retinal damage.
AB  - Selegiline, a therapeutic agent of Parkinson's disease, and its metabolite,
      desmethylselegiline, were explored for their neuroprotective effects against N
      methyl-D-aspartate (NMDA)-induced cell death in rat retina. Morphometric analysis
      of the retina revealed that an intravitreal injection of NMDA induced a
      significant decrease in cell density in the ganglion cell layer and in thickness
      of the inner plexiform layer, but not of other retinal layers such as the outer
      nuclear layer. Concurrent intravitreal injection of selegiline with NMDA did not
      show a significant protective effect, whereas co-injection of desmethylselegiline
      provided protection from NMDA-induced retinal damage. Parenteral administration
      (both single and consecutive dosing) of selegiline significantly prevented loss
      of ganglion cell layer cells. Counting of retinal ganglion cells by fluorescent
      tracer labeling confirmed that selegiline protected retinal ganglion cells from
      NMDA toxicity. The selegiline treatment did not produce a significant increase,
      though it tended to such as effect, in a brain-derived neurotrophic factor (BDNF)
      level in the retina, when compared with the NMDA-treated control group. These
      results indicate that parenteral treatment with selegiline rescues inner retinal
      cells from NMDA-induced neural damage, and that desmethylselegiline may
      contribute, in part, to the protective activities of selegiline. The
      neuroprotective effects exerted by selegiline may be attributed partially to a
      change in the retinal BDNF expression.

PMID- 12498911
TI  - Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the
      spinal reflex transmission through 5-HT(2) receptors.
AB  - The centrally acting muscle relaxant cyclobenzaprine decreases the amplitude of
      monosynaptic reflex potentials by inhibiting the facilitatory descending
      serotonergic influences in the spinal cord. Interestingly, the structure of
      cyclobenzaprine is much similar to those of amitriptyline and cyproheptadine. In
      the present study, we attempted to elucidate the relationship between 5-HT(2)
      receptor antagonistic and inhibitory effects of cyclobenzaprine, amitriptyline,
      cyproheptadine and ketanserin on the spinal reflexes. Cyclobenzaprine,
      amitriptyline, cyproheptadine, and ketanserin significantly inhibited
      facilitatory effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on
      flexor reflexes and mono- and polysynaptic spinal reflex potentials in spinalized
      rats. In intact rats, these drugs significantly reduced the mono- and
      polysynaptic reflex potentials. 5-HT depletion significantly prevented the
      depression of the spinal reflex potentials induced by these drugs. These results
      suggest that the inhibitory effects of cyclobenzaprine, amitriptyline, and
      cyproheptadine on mono- and polysynaptic reflex potentials are due to the
      inhibition of descending serotonergic systems through 5-HT(2) receptors in the
      spinal cord.

PMID- 12498912
TI  - Functional interactions between delta- and mu-opioid receptors in rat
      thermoregulation.
AB  - The selective delta-opioid receptor agonist deltorphin II (25.0-100.0 microg,
      i.c.v.) produced biphasic effects on core temperature in rats, in which
      hypothermia was followed by hyperthermia. Pretreatment with the selective delta
      opioid receptor antagonist, naltrindole (25.0 microg, i.c.v.), blocked
      hypothermia produced by deltorphin II and had a tendency to potentiate the
      hyperthermic effect of deltorphin II. The non-selective opioid receptor
      antagonist naloxone (1.5 mg kg(-1), s.c.) potentiated hypothermia, and blocked
      hyperthermia, produced by deltorphin II (100.0 microg). Also, naloxone
      potentiated hypothermia produced by a lower dose of deltorphin II (25.0 microg),
      which did not produce hyperthermia. A similar pattern was found for the selective
      mu-opioid receptor antagonist, beta-funaltrexamine (5.0 microg, i.c.v.), which
      potentiated and blocked deltorphin II-induced hypo- and hyperthermia,
      respectively. The selective kappa-opioid receptor antagonist nor-binaltorphimine
      (20.0 microg, i.c.v.) had no effects on deltorphin II-induced temperature
      changes. The present results suggest that deltorphin II produces hypothermia
      through activation of delta-opioid receptors, whereas the hyperthermic effect of
      deltorphin II involves activation of mu-opioid receptors. This mu-opioid receptor
      stimulatory effect of deltorphin II is furthermore more pronounced than was
      anticipated based on the reported in vitro properties of this compound. The
      biphasic effect of deltorphin II implies a negative interaction between delta-
      and mu-opioid receptors in thermoregulation in rats.

PMID- 12498913
TI  - The NMDA receptor NR2B subtype selective antagonist Ro 25-6981 aggravates
      paroxysmal dyskinesia in the dt(sz) mutant.
AB  - Previously, enhanced levels of spermine which stimulates N-methyl-D-aspartate
      (NMDA) receptors, particularly those containing the NR2B subunit, were found in
      brains of dt(sz) mutant hamsters, a model of paroxysmal dyskinesia in which
      dystonic episodes occur in response to stress. Therefore, the effects of the NR2B
      selective NMDA receptor antagonist Ro 25-6981 ([R-(R,S)]-alpha-(4-hydroxyphenyl)
      beta-methyl-4-phenyl-methyl)-1-piperidine-propanol] on severity of dystonia were
      investigated in the dt(sz) hamster. Ro 25-6981 failed to exert antidystonic
      effects, but even caused a moderate aggravation at higher doses (10.0, 12.5
      mg/kg). This result indicates that overstimulation of receptors that include the
      NR2B subunit by polyamines is not involved in the dystonic syndrome. NR2B
      selective NMDA receptor antagonists seem not to provide a novel approach in the
      treatment of hereditary paroxysmal dyskinesias.

PMID- 12498914
TI  - Blockade of nicotine-induced locomotor sensitization by a novel neurotensin
      analog in rats.
AB  - Neurotensin is a tridecapeptide with anatomic and functional relationships to
      dopaminergic neurons. Previously we showed that one of our brain-penetrating
      neurotensin analogs, NT69L (N-met-L-Arg, L-Lys, L-Pro, L-neo-Trp, L-tert-Leu, L
      Leu), blocks cocaine- and D-amphetamine-induced hyperactivity in rats. We have
      now performed a similar study in rats sensitized to nicotine over 15 days of
      administration. Male Sprague-Dawley rats were randomly assigned to receive daily
      injections for 15 days with one of the following combinations: saline/nicotine
      (0.35 mg/kg), NT69L (1 mg/kg)/nicotine, saline/saline, or NT69L/saline with a 30
      min period between injections. On day 15 each group was given saline/nicotine or
      NT69L/nicotine and tested in an activity chamber. One-time administration of
      NT69L attenuated nicotine-induced activity with an ED(50) of 1.6 microg/kg. Rats
      injected with nicotine over the 15 days had a significant increase in locomotor
      activity, consistent with nicotine-induced locomotor sensitization. A single
      injection of NT69L on day 15 prior to nicotine markedly decreased nicotine
      induced hyperactivity. Although daily injections of NT69L lessened its effect,
      statistically significant reductions in hyperactivity to nicotine persisted
      throughout the study. There was no significant difference in activity between
      rats injected with NT69L/saline and saline/saline. Thus, the activity reduction
      was not due to sedation. Acute and chronic nicotine injection caused an increase
      in cytisine binding in prefrontal cortex. NT69L significantly reduced the
      increase caused by acute but not chronic injection of nicotine. Nicotine
      injection resulted in an increase in dopamine levels in the striatum and dopamine
      and norepinephrine levels in the prefrontal cortex. NT69L lowered the
      norepinephrine and dopamine levels in the prefrontal cortex but did not affect
      striatal dopamine. The present study is the first report, to our knowledge, of a
      possible role for neurotensin in the development of nicotine dependence, and
      suggests that neurotensin analogs such as NT69L may be explored as treatment for
      nicotine and other psychostimulant abuse.

PMID- 12498915
TI  - Nitric oxide within the ventral tegmental area is involved in mediating morphine
      reward.
AB  - In the present study, the effects of intra-ventral tegmental area injection of L
      arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester
      (L-NAME), a nitric oxide synthase (NOS) inhibitor, on morphine-induced
      conditioned place preference in male Wistar rats were investigated. Our data
      showed that subcutaneous (s.c.) injection of morphine sulphate (0.5-10 mg/kg)
      significantly increased the time spent in the drug-paired compartment in a dose
      dependent manner. Intra-ventral tegmental area administration of a low dose of L
      arginine (0.05 microg/rat) with an ineffective dose of morphine (0.5 mg/kg)
      elicited significant conditioned place preference; however, a higher dose of L
      arginine (0.1 microg/rat) reduced the morphine response. Intra-ventral tegmental
      area administration of L-NAME (0.03 and 0.1 microg/rat) decreased the acquisition
      of morphine (7.5 mg/kg)-induced place preference. The response to different doses
      of L-arginine was decreased by L-NAME (0.03 microg/rat). L-Arginine and L-NAME by
      themselves did not elicit any effect on place conditioning; however, intra
      ventral tegmental area administration of L-arginine (0.01-0.1 microg/rat) and a
      higher dose of L-NAME (0.1 microg/rat) significantly decreased the expression of
      morphine (7.5 mg/kg)-induced place preference. The attenuation of already
      established morphine-induced place preference on the test day by L-arginine was
      inhibited by L-NAME (0.03 microg/rat). The results indicate that NO may be
      involved in the acquisition and expression of morphine-induced place preference.

PMID- 12498916
TI  - Reversal of antidepressant-induced dopaminergic behavioural supersensitivity
      after long-term chronic imipramine withdrawal.
AB  - Chronic antidepressant treatments enhance dopaminergic neurotransmission in the
      mesolimbic dopamine system. We suggested that this potentiation might underlie
      both the antidepressant therapeutic effect and the antidepressant-induced switch
      from depression to mania, which in turn, might be involved in the development of
      rapid cycling in bipolar patients. In this study, we investigated the changes
      occurring in the sensitivity of the mesolimbic dopamine system up to 40 days
      after antidepressant withdrawal. Male Sprague-Dawley rats were treated for 3
      weeks with imipramine (20 mg/kg) and tested for motor activity 24 h, 12, 33 and
      40 days after treatment withdrawal. Ambulatory activity and rearing counts were
      recorded after challenge with the dopamine D2-like receptor agonist quinpirole
      (0.15 mg/kg). Imipramine increased the motor response to quinpirole, 24 h after
      treatment discontinuation. No relevant differences between the groups were found
      after 12 and 33 days. After 40 days, a decreased level of rearing was observed in
      the group treated with imipramine. These results show a reversal of the
      imipramine-induced dopaminergic supersensitivity after 40 days of chronic
      imipramine withdrawal and suggest that the mood-switches observed in bipolar
      patients following antidepressant treatment and subsequent withdrawal, i.e. mania
      followed by rebound depression, might depend upon parallel changes in the
      mesolimbic dopamine system sensitivity.

PMID- 12498917
TI  - Modulation of stress-induced neurobehavioral changes by nitric oxide in rats.
AB  - The involvement of nitric oxide (NO) in stress-induced neurobehavioral changes in
      rats was evaluated using the elevated plus maze and open field tests. Restraint
      stress (1 h) reduced both the number of entries and time spent in open arms, with
      both expressed as percent of controls (no restraint stress), and these changes
      were reversed with diazepam (1 mg/kg) and the NO precursor, L-arginine (500 and
      1000 mg/kg) pretreatment. The nitric oxide synthase inhibitor, N-nitro-L-arginine
      methyl ester (L-NAME) (50 mg/kg), aggravated restraint stress effects in the
      elevated plus maze test, whereas the lower dose (10 mg/kg) of the drug attenuated
      the same. In the open field test, the restraint stress-induced (a) increased
      entry latency and (b) decreased ambulation and rearing were reversed by diazepam
      and L-arginine and L-NAME (10 mg/kg), whereas L-NAME (50 mg/kg) aggravated
      restraint stress effects. The neuronal nitric oxide synthase inhibitor, 7
      nitroindazole (10 and 50 mg/kg), did not influence these restraint stress-induced
      behavioral changes to any significant extent. Biochemical data showed that L-NAME
      (10 and 50 mg/kg.) induced opposite effects on the total brain nitrate/nitrite
      content during restraint stress. The results indicate a possible involvement of
      NO in stress-induced neurobehavioral effects.

PMID- 12498918
TI  - The 5-HT1A receptor agonist MKC-242 increases the exploratory activity of mice in
      the elevated plus-maze.
AB  - The effect of (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3
      benzodioxole HCl (MKC-242), a 5-HT(1A) receptor agonist, on mouse behavior was
      examined in the elevated plus-maze. MKC-242 significantly increased the
      percentage of open-arm entries and the percentage of open-arm time, indices of
      anxiety reduction, while it did not increase the enclosed-arm entries and time
      spent in enclosed arms. The effect of MKC-242 was antagonized by a low dose of
      the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N
      (2-pyridinyl)cyclohexanecarboxamide which alone did not affect the behavior.
      These findings suggest that MKC-242 increases the exploratory activity of mice in
      the elevated plus-maze via activation of 5-HT(1A) receptors, probably the
      presynaptic autoreceptors.

PMID- 12498919
TI  - NS-398, a selective cyclooxygenase-2 blocker, acutely inhibits receptor-mediated
      contractions of rat aorta: role of endothelium.
AB  - NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)-methane sulfonamide) is a selective
      inhibitor of the cyclooxygenase-2 isozyme in vitro and in vivo. This study
      reports on acute inhibition of receptor-mediated contractions of isolated rat
      aorta by NS-398 and its modulation by endothelium-derived nitric oxide. NS-398 (1
      10 microM) blocked norepinephrine, and 5-hydroxytryptamine (5-HT) evoked
      contractions and suppressed E(max) responses for both agonists. E(max) changes
      occurred in endothelium-intact vessel rings and in the absence, as well as in the
      presence of cycloheximide or dexamethasone in the physiological salt solution
      (PSS) bathing the tissues. NS-398 altered contractions to these receptor agonists
      in denuded rings only at 10 microM, and did not significantly alter contractions
      to KCl and sodium fluoride in all situations. NS-398 (3 and 10 microM) reduced
      aortic contractions initiated by cyclopiazonic acid (CPA), a sarcoplasmic
      reticulum Ca(2+)-ATPase blocker, in endothelium intact rings bathed with PSS
      with/without nitro-D-arginine methyl ester (D-NAME; 100 microM), but did not
      alter contractions to the compound in endothelium-denuded aortic rings and in
      vessel rings bathed with PSS+L-NAME (100 microM). Western blot analyses reveal
      significantly denser cyclooxygenase-2 protein expressions in freshly isolated
      endothelium-intact, compared to, denuded vessel segments. We conclude that: (1)
      cyclooxygenase-2 is constitutively expressed in rat aortic endothelial and smooth
      muscle cells, and (2) NS-398 modulates aortic contractions principally through an
      action on endothelial cyclooxygenase-2. Our data strongly suggest that
      cyclooxygenase-2 and/or its product(s), in concert with endothelium-derived
      nitric oxide, regulates the sarcoplasmic reticulum Ca(2+) pump activity in rat
      aorta.

PMID- 12498920
TI  - Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+
      exchanger, on myocardial ischemia-reperfusion injuries.
AB  - The Na(+)/Ca(2+) exchanger (NCX) is involved in myocardial ischemia-reperfusion
      injuries. We examined the effects of 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5
      ethoxyaniline (SEA0400), a potent and selective inhibitor of NCX, on myocardial
      ischemia-reperfusion injury models. In canine cardiac sarcolemmal vesicles and
      rat cardiomyocytes, SEA0400 potently inhibited the Na(+)-dependent 45Ca(2+)
      uptake with an IC(50) value of 90 and 92 nM, compared with 2-[2-[4-(4
      nitrobenzyloxy)phenyl]isothiourea (KB-R7943, 7.0 and 9.5 microM), respectively.
      In rat cardiomyocytes, SEA0400 (1 and 3 microM) attenuated the Ca(2+) paradox
      induced cell death. In isolated rat Langendorff hearts, SEA0400 (0.3 and 1
      microM) improved the cardiac dysfunction induced by low-pressure perfusion
      followed by normal perfusion. In anesthetized rats, SEA0400 (0.3 and 1 mg/kg,
      i.v.) reduced the incidence of ventricular fibrillation and mortality induced by
      occlusion of the left anterior descending coronary artery followed by
      reperfusion. These results suggest that SEA0400 is a most potent NCX inhibitor in
      the heart and that it has protective effects against myocardial ischemia
      reperfusion injuries.

PMID- 12498921
TI  - The indirect negative inotropic effect of carbachol in beta1-adrenoceptor
      antagonist-treated human right atria.
AB  - To find out whether indirect negative inotropic effects of carbachol (i.e.
      decreases in force of contraction that had been stimulated by cyclic AMP
      increasing agents) might differ dependent on the agonist employed to increase
      contractile force in isolated human right atrium, we studied effects of carbachol
      on atria prestimulated with noradrenaline, terbutaline, histamine and serotonin.
      All four agonists increased right atrial adenylyl cyclase activity and
      contractile force, whereby increases for terbutaline, histamine and serotonin,
      but not for noradrenaline, were significantly larger in right atria from beta(1)
      adrenoceptor antagonist-treated vs. non-beta(1)-adrenoceptor antagonist-treated
      patients. Carbachol (10(-8)-10(-3) M) concentration-dependently decreased agonist
      stimulated contractile force: maximum decrease was not significantly different
      within the four agonists. pD(2) values for carbachol, however, were higher in
      atria from non-beta(1)-adrenoceptor antagonist-treated vs. beta(1)-adrenoceptor
      antagonist-treated patients.We conclude that, in isolated human right atria,
      carbachol-induced indirect negative inotropic effect is not dependent from the
      agonist employed to increase (via cyclic AMP accumulation) contractile force.
      However, in atria from beta(1)-adrenoceptor antagonist-treated patients,
      carbachol-induced indirect negative inotropic effect is attenuated.

PMID- 12498922
TI  - Nuclear factor-kappaB inhibitors abolish hypoxic vasoconstriction in sheep
      isolated pulmonary arteries.
AB  - The aim of this study was to determine the role of nuclear factor-kappaB (NF
      kappaB) in hypoxic constriction of isolated pulmonary arteries. Rings were
      suspended in an organ bath filled with Krebs-Henseleit solution and isometric
      contractions were recorded continuously. Hypoxia (%95 N(2)-%5 CO(2)) had no
      marked effect on resting force in artery rings. However, hypoxia caused further
      contractions in serotonin-precontracted arteries. Hypoxia-induced
      vasoconstrictions were abolished by preincubation with NF-kappaB inhibitors,
      pyrrolidine dithiocarbamate (100 microM) or pyrithione (10 microM). These results
      suggest that reactive oxygen species and/or NF-kappaB activation may be involved
      in the hypoxia-induced vasoconstriction in sheep-isolated pulmonary arteries.

PMID- 12498923
TI  - Study of the mechanisms involved in the bradykinin-induced contraction of the pig
      iris sphincter muscle in vitro.
AB  - This study was designed to investigate the mechanisms by which bradykinin induces
      contraction of the pig iris sphincter muscle in vitro. Addition of bradykinin,
      Lys-bradykinin and Met-Lys-bradykinin to the pig iris sphincter resulted in a
      graded contraction with a mean EC(50s) of 21, 11 and 5 nM, respectively. The
      bradykinin B(1) receptor agonist des-Arg(9)-bradykinin only caused a slight
      contraction, measured 6 h after the tissue was set up. The B(2) receptor
      antagonists FR 173657 ((E)-3-(6-acetamido-3-pyridyl)-N [N-2-4-dichloro-3-[(2
      methyl-8-quinolinyl) oxymethyl] phenyl]-N-methylamino-carbonyl-ethyl] acrylamide)
      and Hoe 140 (D-Arg(0)-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin produced a
      graded shift to the right associated with marked inhibition of the bradykinin
      induced contraction. Atropine, guanethidine or tetrodotoxin significantly reduced
      the bradykinin-induced contraction. Dazoxiben, an inhibitor of thromboxane A(2),
      and MK-571 (3-(3-(2-(7-chloro-2-quinolinyl) ethenyl) phenyl ((3-dimethyl amino
      3oxo-propyl) thio) methyl) propanoic acid, a leukotriene D(4) receptor-selective
      antagonist, also caused inhibition of the bradykinin-mediated contraction.
      Cyclooxygenase-1 and -2 inhibitors, indomethacin, ibuprofen, valeryl salicylate
      and NS 398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]methanosulfonamide) all
      significantly inhibited the bradykinin-mediated contraction without affecting the
      carbachol-induced contraction of the pig iris sphincter. Taken together, these
      results indicate that the bradykinin-mediated contraction of the pig iris
      sphincter muscle seems to be mediated primarily by the activation of the B(2)
      receptor release of acetylcholine, noradrenaline and both cyclooxygenase-1 and -2
      metabolites besides the release of leukotriene D(4) and tromboxane A(2) from the
      arachidonic acid pathway.

PMID- 12498924
TI  - YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and
      facilitates penile erection in rats.
AB  - The aim of present study was to characterize the in vitro and in vivo
      pharmacological effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl
      indazole), a soluble guanylate cyclase activator, on corpus cavernosal smooth
      muscle and penile erectile activity. YC-1 relaxed phenylephrine precontracted
      cavernosal smooth muscle (EC(50)=4.4 microM) and this effect was partially
      antagonized by 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ). ODQ is a
      selective soluble guanylate cyclase inhibitor that completely blocked the
      relaxation induced by sodium nitroprusside, suggesting that YC-1 binds to soluble
      guanylate cyclase at a different site from nitric oxide (NO). Both YC-1 and
      sodium nitroprusside, but not sildenafil (1-100 microM) caused concentration
      dependent increases in cyclic GMP levels in cultured rabbit cavernosal smooth
      muscle cells and produced synergistic effects. Intraperitoneal administration of
      YC-1 (10 micromol/kg) evoked penile erection in rats with 70% incidence. More
      importantly, YC-1 was able to significantly augment the pro-erectile effects of a
      suboptimal dose of apomorphine. These results suggest that the soluble guanylate
      cyclase activator YC-1 increases cyclic GMP levels, leading to relaxation of
      cavernosal smooth muscle. These biochemical events may be related to the pro
      erectile properties of YC-1 in vivo.

PMID- 12498925
TI  - The role of Ca2+ in the control of renin release from dog renal cortical slices.
AB  - Using a continuous superfusion system of dog renal cortical slices, we studied
      the role of Ca(2+) in the intracellular control mechanism for renin release. The
      calcium ionophore A23187 (10 microM) produced a significant decrease in renin
      release. This effect was abolished in the absence of extracellular Ca(2+).
      Moreover, pretreatment with the calmodulin inhibitor W-7 (N-(6-aminohexyl)-5
      chloro-1-naphthalenesulfonamide, 20 microM) completely prevented the inhibitory
      effect of A23187 (10 microM). The beta-adrenoceptor agonist isoproterenol (1, 10
      and 100 microM) produced a concentration-dependent increase in renin release.
      Pretreatment with W-7 (20 microM) potentiated the stimulation of renin release
      induced by isoproterenol (1 microM). These results suggest that A23187-induced
      inhibition of renin release is mediated by the activation of calmodulin via an
      increase in intracellular Ca(2+) and beta-adrenoceptor-stimulated renin release
      is modulated by intracellular Ca(2+) mobilization.

PMID- 12498926
TI  - Adenosine A1 receptor blockade reverses experimental postoperative ileus in rat
      colon.
AB  - Inhibition of colonic propulsive motility is the main contributor to
      postoperative ileus in humans. Experimental models for investigating colonic
      propulsion in surgically induced postoperative ileus have not previously been
      available. This study was designed to assess whether adenosine A(1) receptor
      antagonists (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]
      piperidin-2-yl acetic acid (FK352) and 8-cyclopentyl-1, 3-dipropylxanthine
      (DPCPX) reverse the colonic motility disorder in newly developed rat experimental
      ileus models. When rats underwent anesthesia (pentobarbital) or surgical traumas
      (partial gastrectomy, cecectomy or gentle touching of the colon with fingers),
      colonic propulsive motility was evaluated by migration of intracolonically
      injected dye in awake unrestrained rats. Propulsive motility resulted in
      significant decrease after the treatment of the anesthesia or partial
      gastrectomy. Intravenous administration of either adenosine A(1) receptor
      antagonist reversed the slowed colonic propulsion in these experimental ileus
      models. The present study suggests that the blockade of adenosine A(1) receptors
      has therapeutic potential for postoperative ileus.

PMID- 12498927
TI  - Vas deferens response to selective opioid receptor agonists in adult mice is
      impaired following postnatal repeated mild stress.
AB  - Mild stress repeatedly applied to neonatal rodents induces alterations of central
      nervous system functions, persisting up to the adult age. Most alterations may be
      mediated through hormones and neuromediators active on the autonomic nervous
      system, therefore we tested the efficacy of selective opioid receptor agonists on
      the vas deferens of adult mice that, as neonates, had undergone daily mild stress
      until weaning (brief isolation and solvent injection). We found in the adult
      mouse (90 days old) decreased sensitivity of vas deferens to selective mu-, delta
      and kappa-opioid receptor agonist drugs. The neonatal administration of an
      antisense oligodeoxynucleotide adrenocorticotropin-synthesis-inhibitor partly
      prevented these effects.

PMID- 12498928
TI  - Inhibition of interleukin-8 release in the human colonic epithelial cell line HT
      29 by cannabinoids.
AB  - We have investigated the effects of cannabinoid agonists and antagonists on
      tumour necrosis factor-alpha (TNF-alpha)-induced secretion of interleukin-8 from
      the colonic epithelial cell line, HT-29. The cannabinoid receptor agonists [(-)-3
      [2-hydroxy-4-(1,1-dimethyl-heptyl)-phenyl]4-[3-hydroxypropyl]cyclo-hexan-1-ol]
      (CP55,940); Delta-9-tetrahydrocannabinol; [R(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl) methyl] pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl)
      methanone mesylate] (WIN55,212-2) and 1-propyl-2-methyl-3-naphthoyl-indole (JWH
      015) inhibited TNF-alpha induced release of interleukin-8 in a concentration
      dependent manner. The less active enantiomer of WIN55212-2, [S(-)-[2,3-dihydro-5
      methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]1,4-benzoxazin-6-yl](1-naphthyl)
      methanone mesylate (WIN55212-3), and the cannabinoid CB(1) receptor agonist
      arachidonoyl-2-chloroethylamide (ACEA) had no significant effect on TNF-alpha
      induced release of interleukin-8. The cannabinoid CB(1) receptor antagonist N
      (piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1,4-pyrazole
      3-carboxamide hydrochloride (SR141716A; 10(-6) M) antagonised the inhibitory
      effect of CP55,940 (pA(2)=8.3+/-0.2, n=6) but did not antagonise the inhibitory
      effects of WIN55212-2 and JWH 015. The cannabinoid CB(2) receptor antagonist N
      (1,S)-endo1,3,3-trimethylbicyclo(2,2,1)heptan-2-yl)-5(4-chloro-3-methyl-phenyl)-1
      (4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 10(-6) M) antagonised the
      inhibitory effects of CP55,940 (pA(2)=8.2+/-0.8, n=6), WIN55212-2 (pA(2)=7.1+/
      0.3, n=6) and JWH 015 (pA(2)=7.6+/-0.3, n=6), respectively. Western
      immunoblotting of HT-29 cell lysates revealed a protein with a size that is
      consistent with the presence of cannabinoid CB(2) receptors. We conclude that in
      HT-29 cells, TNF-alpha-induced interleukin-8 release is inhibited by cannabinoids
      through activation of cannabinoid CB(2) receptors.

PMID- 12498929
TI  - Piperlactam S suppresses macrophage migration by impeding F-actin polymerization
      and filopodia extension.
AB  - This study was designed to evaluate the anti-inflammatory effect of piperlactam S
      on chemoattractant-induced migration, functions underlying leukocyte recruitment
      in vitro. Results showed that RAW264.7 macrophages migrate toward complement 5a,
      a powerful chemoattractant for macrophages. This phenomenon could be suppressed
      concentration dependently by piperlactam S (0.3-30 microM). Fluorescence staining
      demonstrated that piperlactam S and cytochalasin B both effectively reversed
      complement 5a-induced cell polarization, filopodia extension, as well as the
      increase in the cell content of F-actin. Functional inhibition by antibodies
      suggested that Mac-1 (CD11b) integrin plays a central role in complement 5a
      induced migration. However, piperlactam S failed to modify Mac-1 expression.
      Furthermore, complement 5a triggered the activation of Cdc42, a Rho-family
      protein involved in the regulation of filopodia extension, with a time course
      that paralleled that of filopodia extension and which was inhibited by
      piperlactam S. In summary, piperlactam S exerts anti-inflammatory effects
      possibly by interfering with cell migration, impeding F-actin polymerization,
      filopodia formation, and/or Cdc42 activation. However, the detailed mechanism by
      which piperlactam S regulates the above processes needs further study.

PMID- 12498930
TI  - Long-term oral nicotine administration reduces insulin resistance in obese rats.
AB  - This study aimed to investigate the effect of long-term oral nicotine
      administration on insulin resistance in an animal model of obesity. Eight-week
      old male Zucker fatty rats (ZFRs) were administered nicotine tartrate dihydrate
      (4.6 mg/kg/day) in the drinking water. The control group was pair-fed. The body
      weights and food intake over 8 weeks were similar in both groups. Plasma glucose
      levels at 3, 6, 9, 12, and 15 min after insulin administration (0.5 U/kg) in the
      nicotine group were significantly lower than those in the control group. The
      calculated K(ITT) value for the nicotine group was significantly higher than that
      for the control group. Wet weight of the liver in the nicotine group was
      significantly lower than that in the control group. Transaminases and
      histological examination of the liver revealed no alteration by nicotine
      administration. Glycogen, glycogen synthetase activity and gluconeogenesis in the
      liver in the nicotine group were significantly lower than those in the control
      group. Phosphorylase-a activity of the liver in the nicotine group was
      significantly higher than that in the control group. Glycogen, glycogen
      synthetase, and phosphorylase-a activity of skeletal muscle were similar in both
      groups. These results suggest that long-term oral nicotine administration may
      reduce insulin resistance in obese diabetic rats through a reduced hepatic
      glucose release and, in part, contribute to lowering blood glucose levels.

PMID- 12498931
TI  - Sonography of the common bile duct and the gallbladder during ceruletid infusion.
AB  - In the present study, we investigated a new sonographic test to confirm or
      exclude partial common bile duct (CBD) obstruction, hereinafter called "dynamic
      cholangio-cholecysto sonography (DCCS)." Healthy controls (6) and patients with
      low- to intermediate probability for partial CBD obstruction (17) were
      investigated. DCCS started with three baseline masurements of gallbladder volume
      and CBD diameter, which were then repeated every 2 to 3 min for 45 min during a
      30-min infusion of ceruletid. According to CBD diameter change during gallbladder
      contraction, DCCS was considered positive (> 1 mm), negative (< 0.5 mm) or
      equivocal (remainder). After DCCS, all patients underwent endoscopic retrograde
      cholangiography (ERCP) and all but one patient had endoscopic sphincterotomy
      (EST). A follow-up examination was performed at least 4 weeks after ERCP. Based
      on these results, an outcome score was calculated to classify the patients as
      having a flow-relevant CBD obstruction or not. DCCS was true positive in 4
      patients (sensitivity 66%, positive predictive value 100%). DCCS was false
      negative in 1 patient and equivocal in another patient. DCCS was true-negative in
      9 patients (specifity 82%, negative predictive value 90%). Two patients without
      flow-relevant CBD obstruction had equivocal DCCS test results. DCCS might be used
      as a noninvasive test for further workup of patients with low- to intermediate
      probability of flow relevant CBD obstruction, helping to avoid unnecessary ERCP
      and to serve as an additional indication for ERCP and EST.

PMID- 12498932
TI  - Assessment of fetal adrenal gland volume using three-dimensional ultrasound.
AB  - To assess the normal fetal adrenal gland volume during normal gestation, we
      performed a prospective study on 119 normal fetuses with gestational age ranging
      from 21 to 40 weeks using a 3-D ultrasound (US) volume scanner with a pure cross
      sectional design. Polynomial regression analysis was calculated to find the best
      fit model between gestational age (GA) and adrenal gland volume. In addition,
      estimated fetal weight (EFW) was also measured to demonstrate the correlation
      between adrenal gland volume and fetal weight. Our results showed that fetal
      adrenal gland volume is highly correlated with GA. Furthermore, using GA as the
      independent variable and adrenal gland volume as the dependent variable, the best
      fit regression equation was adrenal glands volume (mL) = -0.2683 x GA + 0.0082 x
      GA(2) + 3.1927 (r = 0.93, n = 119, p < 0.0001). For clinical use, a chart of
      normal growth centiles of fetal adrenal gland volume in utero was then calculated
      based on this equation. In addition, fetal adrenal gland volume during normal
      gestation is also highly correlated with EFW (p < 0.0001). In conclusion, our
      data of fetal adrenal gland volume assessed by 3-D US can serve as a useful
      reference in evaluating fetal growth status during gestation.

PMID- 12498933
TI  - Volume quantification of intracardiac mass lesions by transesophageal three
      dimensional echocardiography.
AB  - As compared with two-dimensional (2-D) transesophageal echocardiography (TEE), 3
      D echocardiography now permits more realistic visualization of cardiac anatomy
      and of intracardiac lesions. The aim of this study was to apply newer 3-D
      echocardiographic techniques to quantify volumes of intracardiac masses
      undergoing surgical resection seen during an intraoperative TEE. The calculated
      volumes were compared with actual in vitro measurements of surgically resected
      masses. A total of 14 patients (9 men; 5 women; age range between 21 and 77
      years) with intracardiac mass lesions (4 tumors: 3 left atrial myxomas and 1
      mitral valve fibroelastoma, and 10 vegetations: 5 aortic valve, 3 mitral valve, 1
      tricuspid and 1 pulmonary valve) were studied. Using commercially available 3-D
      reconstruction software (TomTec v. 4.1), the volumes of intracardiac masses were
      estimated using both the average rotation (rotation around the long axis, AR) and
      disk summation (parallel short axis cuts, DS) methods. Volumes of these lesions
      were also measured in vitro by water submersion. They ranged from 0.20 mL to 24
      mL (mean +/- SD = 8.07 +/- 9.21 mL). Both 3-D TEE AR and 3-D TEE DS calculated
      volumes correlated excellently with in vitro measured volumes (r = 1.00 and r =
      0.98, respectively, p = < 0.0001). The correlation between 3-D TEE AR and 3-D TEE
      DS calculated volumes was also excellent (r = 0.98, p = < 0.0001). In conclusion,
      the volume assessments by 3-D TEE of intracardiac mass lesions correlated well
      with in vitro measured volumes of surgical specimens. This technique may prove to
      be valuable in further defining intracardiac pathology and is a further
      advancement toward the application of clinically useful 3-D echocardiography.

PMID- 12498934
TI  - Left ventricular transmural systolic function by high-sensitivity velocity
      measurement "phased-tracking method" across the septum in doxorubicin
      cardiomyopathy.
AB  - The clinical usefulness of doxorubicin is limited by doxorubicin-induced
      cardiomyopathy (DoxCM). The prognosis of this disorder is poor, and a sensitive
      noninvasive method for detection of DoxCM is strongly required. In this study, we
      examined if the transmural systolic function (TSF) obtained by the novel phased
      tracking method is capable of supplying new information on DoxCM. A total of 18
      healthy subjects and 30 patients with acute lymphoblastic leukemia were examined
      for TSF, as defined by the transmural profile of % thickening obtained by
      measuring the velocity at each preset point of 0.75-mm intervals. The total
      number of measurements was 94. In the patients, a decrease in both the peak
      velocity and the systolic layer thickening was observed, even in the subclinical
      phase of the normal ejection fraction. For healthy subjects, systolic thickening
      occurred in the left ventricular (LV) side of the interventricular septum (IVS),
      and was characterized by a sharp single-peak configuration of the profile. For
      the patients, however, the peak became dull and/or unclear, which indicates that
      a change in transmural functional distribution occurred. We concluded that the
      TSF is a useful measure for diagnosis of the early phase of DoxCM.

PMID- 12498935
TI  - Prognostic and diagnostic value of global cerebral blood flow volume and cerebral
      transit time in acute stroke.
AB  - Conventional duplex sonography is a well-established method for the assessment of
      the brain-supplying arteries in acute stroke. However, ultrasound (US) remains
      inconclusive in a significant number of stroke patients. Recently, two new US
      parameters, the cerebral transit time (cTT) and the global cerebral blood flow
      volume (CBF), have been introduced. In the present study, we investigated the
      diagnostic and prognostic value of both parameters in stroke patients.
      Conventional duplex examinations of the extra- and intracranial brain-supplying
      arteries and measurement of cTT and CBF were performed in 50 consecutive stroke
      patients within 24 h after symptom onset and compared with US findings in 22 age
      matched healthy controls. Neurological deficits and the degree of disability were
      graded using several stroke scores, and were re-evaluated for outcome measure
      after 1 year. CBF and cTT were not assessable in 26% and 20% of the patients,
      respectively. Compared with the healthy control group, stroke patients showed a
      significant reduction of CBF and prolongation of cTT. More than 50% of patients
      with otherwise normal routine duplex examination had abnormal CBF or cTT
      findings. Furthermore, there was a strong correlation between the reduction of
      global CBF and the outcome after 1 year. Sonographic assessment of the CBF and
      cTT are additional parameters that might increase the diagnostic sensitivity of
      US in stroke patients, and may have prognostic relevance.

PMID- 12498936
TI  - Ultrasound measurement of the effect of temperature on microperfusion in the eye.
AB  - Recent developments in ultrasound (US) technology have allowed the study of
      microperfusion in the anterior segment of the eye. Our aim was to determine the
      effect of the thermal environment on blood flow in the anterior segment. We
      measured blood flow in the major arterial circle of five rabbits. A 38-MHz US
      transducer was coupled to the eye with a normal saline water-bath with
      temperature controlled from 1 degrees C to 38 degrees C. The major arterial
      circle was localized and imaged using the swept-scan technique and M-mode data
      were then acquired for measurement of pulsatile flow. Peak systolic and mean
      velocity averaged 4.51 and 1.32 mm/s, respectively. Positive correlations were
      found between peak systolic (1.69%/ degrees C) and mean (1.76%/ degrees C)
      velocities and temperature. Vessel diameter (mean = 178 microm) did not show any
      significant change with temperature. High-resolution US flowmetry demonstrated
      decreasing flow rates in the iris with decreasing temperature.

PMID- 12498937
TI  - A transfer function-based mathematical model of the fetal-placental circulation.
AB  - The circulation of a human fetus has been modeled using a transfer function that
      is based on the arterial dimensions at 28 weeks gestational age (GA). These
      dimensions have then been adapted for growth between 28 and 40 weeks GA. The
      input to the model is a series of current pulses at the fetal heart rate, where
      current in the model is analogous to volume blood flow in the fetus. The arterial
      system is divided into short segments that are cascaded together. The respective
      transfer functions are based on the dimensions, wall properties and fluid
      characteristics at each frequency and GA. Bleed off conductances distribute
      current to circuits representing the various anatomical regions. In particular,
      the placenta is simplified to a symmetrically distributed network of branching
      vessels, each represented by a transfer function. All calculations are performed
      in the frequency domain, after which the inverse Fourier transform is used to
      calculate the currents that represent the time-domain blood flow waveforms.
      Simulated flow waveform resistance index and pulsatility index values are within
      8% of those reported for human clinical studies, at all gestational ages.

PMID- 12498938
TI  - Transcranial contrast diminution imaging of the human brain: a pilot study in
      healthy volunteers.
AB  - Analysis of contrast diminution kinetics after bubble destruction is a new aspect
      in harmonic imaging. The purpose of this study was to investigate this approach
      to human cerebral perfusion. A total of 12 healthy volunteers were investigated
      transtemporally (Philips SONOS 5500, S4-probe, 1.8 to 3.6 MHz, 10 cm) at two
      ultrasound (US) contrast agent (UCA) infusion rates (0.5 and 1.0 mL/min of
      Optison). After achieving a steady-state, a set of 12 US pulses (6.67 Hz, MI 1.6)
      was applied. Time-intensity plots of three regions-of-interest (ROIs) (thalamus,
      white matter and cortex) were analyzed, using an exponential curve fit (I((t)) =
      I(0)e(-betat) + B). A total of 20 of 20 successful investigations showed a signal
      decrease after pulsed US application. In all cases, it was possible to generate
      exponential time-intensity curves. Half-life (T(1/2) = ln2/beta) and baseline
      intensity (B) showed a significant dependence on infusion rate (p = 0.01). At 1.0
      mL/min, T(1/2) also depended on investigation depth (p = 0.01). It is possible to
      assess contrast diminution kinetics in human cerebral microcirculation. This new
      approach may provide additional information on cerebral perfusion within a short
      investigation time.

PMID- 12498939
TI  - Microemboli detection using ultrasound backscatter.
AB  - Microemboli detection and characterisation have recently received great attention
      due to its clinical importance in the management of cerebrovascular disease. The
      new method presented in this paper is directly based on the idea that the
      ultrasound (US) backscattered signal from flowing blood is chaotic (El-Brawany
      and Nassiri 2002). The detection technique involves building a nonlinear model of
      the deterministic characteristics of the chaotic backscatter signal from blood,
      and the use of this model to look at the prediction error as a primary decision
      making criterion for the microemboli detector. A complementary feature to the
      prediction error, namely, the degree of coherence between the US excitation pulse
      and the prediction error signal is used to enhance the detection process. The
      detector has been built using a feed-forward neural network with error back
      propagation. The detection technique is tested successfully using a vascular flow
      phantom with solid spheres and bubbles of known sizes introduced in the flow
      circuit to mimic solid and gaseous emboli. Receiver operating characteristic
      (ROC) curve is used to assess the performance of the detection process. The total
      classification rate ranges from 88% to 96%.

PMID- 12498940
TI  - Microembolic signal description: a reappraisal based on a customized digital
      postprocessing system.
AB  - The high variability in presence and signature of microembolic signals (MES),
      detected with transcranial Doppler sonography (TCD) in the middle cerebral artery
      (MCA), cannot be explained with the currently available published data. We
      applied customized postprocessing on the radiofrequency (RF) signal of a standard
      TCD system. The spatial resolution was on the order of 2 mm, depending only on
      the length of the ultrasound (US) burst emitted. The amplitude of clutter
      filtered RF signals was color-coded and plotted as a function of time and depth
      (range 30 mm). Additionally, 128 point fast Fourier transforms (FFTs) (50%
      temporal overlap) were calculated, visualizing both the background Doppler
      spectrum and the MES. We evaluated 122 gaseous MES from two patients during
      cardiac surgery and 52 particulate MES from four patients after carotid
      endarterectomy. Both MES categories showed comparable properties: they appeared
      in the RF amplitude plot as rather straight lines of increased intensity,
      indicating that the velocity remained approximately the same while they passed
      the US beam. The velocity calculated from the amplitude plot never exceeded that
      of the background Doppler spectrum. Various "MES patterns" could be identified
      with respect to the depth range at which the MES were visible. A quarter of the
      gaseous MES changed their direction at a specific depth, suggesting that the MES
      entered a branch (e.g., an M2 artery or the anterior cerebral artery). In the FFT
      analysis, these MES contained both positive and negative frequencies. It is
      concluded that MES show consistent signature patterns in the amplitude-time plots
      and that the previously reported variability of MES appearance in conventional
      Doppler systems is an artefact caused by relatively large signal amplitudes and
      sample volumes.

PMID- 12498941
TI  - Strain during gastric contractions can be measured using Doppler ultrasonography.
AB  - This study was undertaken to explore if strain of the muscle layers within the
      gastric wall could be measured by transabdominal strain rate imaging (SRI), a
      novel Doppler ultrasound (US) method. A total of 9 healthy fasting subjects (8
      women, 1 man; ages 22 to 55 years) were studied and both grey-scale and Doppler
      US data were acquired with a 5- to 8-MHz linear transducer in cineloops of 97 to
      256 frames. Rapid stepwise inflation (5 to 60 mL) of an intragastric bag was
      carried out and bag pressure and SRI were measured simultaneously. SRI enabled
      detailed studies of layers within the gastric wall in all subjects. Great
      variations in strain distribution of the muscle layers were found. Radial strain
      was much higher in the circular than in the longitudinal muscle layer. Strains
      derived from SRI correlated well with strains obtained with B-mode measurements
      (r = 0.98, p < 0.05). During balloon distension, we found an inverse correlation
      between pressure and radial strain (r = -0.87, p < 0.05). Intraobserver
      correlation of strain estimation was r = 0.98 (p < 0.05) and intraobserver
      agreement was 0.2% +/- 18.6% (mean difference +/- 2SD, % strain). Interobserver
      correlation was r = 0.84 (p < 0.05) and interobserver agreement was 6.9% +/-
      56.8%. SRI enables detailed mapping of radial strain distribution of the gastric
      wall and correlates well with B-mode measurements and pressure increments.

PMID- 12498942
TI  - Elastographic imaging of thermal lesions in the liver in vivo following
      radiofrequency ablation: preliminary results.
AB  - Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can
      be used in a percutaneous fashion. This modality provides in situ destruction of
      hepatic tumors. However, local recurrence rates after RF ablative therapy are as
      high as 34% to 55%, believed to be due in part to the inability to visualize
      accurately the zone of necrosis (thermal lesion). This can lead to the incomplete
      ablation of the tumor, generally in areas near the tumor edges. In this paper, we
      show that ultrasound (US)-based in vivo elastography can accurately depict
      thermal lesions after thermal therapy. However, elastography of the liver and
      other abdominal organs is challenging due to the difficulty in providing
      controlled and reproducible compression. The use of the RF ablation probe as the
      compressor/displacement device reduces lateral slippage or nonaxial motion that
      may occur with externally applied compressions or imaging during the respiratory
      cycle. This technique also provides controlled and reproducible compressions of
      the liver for in vivo elastographic imaging. Comparison of elastograms with
      histology of ablated tissue demonstrates a close relationship between
      elastographic image features and histopathology.

PMID- 12498943
TI  - Strain imaging of internal deformation.
AB  - A tissue-like gelatin elasticity-flow phantom was examined to develop ultrasonic
      strain imaging for the detection of internal pulsatile deformations. The same
      imaging technique was then applied in vivo to monitor deformation in tissues
      surrounding the normal brachial artery. The results suggest that vascular strain
      patterns resulting from biologic stimuli are very different from those generated
      using externally applied stress fields, and are directly related to pressure
      variations within the vessel. These data suggest a potential role for strain
      imaging in measuring the relative pressure or vascular elasticity locally and
      noninvasively.

PMID- 12498944
TI  - Ability of ultrasound bone profile score (UBPS) to discriminate between fractured
      and not fractured osteoporotic women.
AB  - In this study, we evaluated the ability of different quantitative ultrasound
      (QUS) parameters (speed of sound, SOS, coefficient of variation, CV, = 0.34% and
      broadband ultrasound (US) attenuation, BUA, CV = 3.25% measured at the heel by an
      Hologic Sahara unit; Ad-Sos and ultrasound bone profile score (UBPS) at the
      proximal phalanges by an Igea DBM Sonic 1200 unit, Ad-Sos CV = 0.57%) to detect
      differences between osteoporotic patients with vertebral fractures and
      osteoporotic patients without fractures. We examined 87 women with primary
      osteoporosis: 53 women with femoral neck bone mineral density (BMD) T scores less
      than -2.5 SD and no vertebral fractures and 34 women with one or more vertebral
      fractures, regardless of T score values. Considering all the patients together,
      the correlations between QUS parameters and BMD resulted in statistical
      significance (p < 0.05) only for BUA and femoral neck BMD. Lumbar and femoral
      neck BMD did not statistically differ between the two groups, while UBPS, which
      is a quality control of measurement and is correlated with bone quality, was
      significantly higher in women without fractures than those with fractures; the
      other QUS parameters were not statistically different. Our data indicate that,
      among QUS parameters, only UBPS is able to detect differences among osteoporotic
      patients with and without vertebral fractures.

PMID- 12498945
TI  - The ability of quantitative ultrasound at the calcaneus to identify
      postmenopausal women with different types of nontraumatic fractures.
AB  - The aim of the cross-sectional study was to determine if ultrasound (US)
      measurements of the calcaneus have the ability to predict the risk for fractures
      and to discriminate between postmenopausal women with and without different types
      of nontraumatic fractures. All women (n = 1,129, age range 40 to 87 years) were
      divided into group 1, created by 656 women with 956 nontraumatic past fractures,
      and group 2, consisting of 473 women without fractures. Group 1 was divided into
      subgroups: with hip fractures, with vertebral (nonhip) fractures, with wrist
      (nonhip and nonspine) fractures and with other (nonhip, nonspine and nonwrist)
      fractures. The speed of sound (SOS; m/s) and broadband ultrasound attenuation
      (BUA; dB/MHz) were measured with the Achilles system (Lunar), which also
      calculates stiffness index (SI; %). US values were significantly lower in group 1
      (1,481.4 +/- 20.2 m/s, 98.7 +/- 9.4 dB/MHz, 61.1 +/- 11.0%; p < 0.000001) and in
      subgroups (p < 0.000001), and these women had a higher mean age and longer
      postmenopausal period than women without fractures (1508.2 +/- 26.5 m/s, 107.7 +/
      9.9 dB/MHz, 74.2 +/- 13.0%). Women with hip fractures had the lowest US values
      (1464.6 +/- 18.6 m/s, 89.9 +/- 8.7 dB/MHz, 50.6 +/- 10.5%), women with vertebral
      fractures had intermediate values (1473.6 +/- 17.4 m/s, 94.8 +/- 8.9 dB/MHz, 56.4
      +/- 10.0%), and women with wrist (1,484.3 +/- 19.8 m/s, 99.9 +/- 9.3 dB/MHz, 62.7
      +/- 10.7%) and other fractures (1,483.3 +/- 21.0 m/s, 100.4 +/- 8.6 dB/MHz, 62.7
      +/- 10.6%) had the highest values. The US values differed significantly between
      subgroups with fractures (p < 0.05), with no significant differences between
      women with wrist and other fractures. ROC analysis showed SOS to have the best
      sensitivity and specificity in detecting fracture cases. All US parameters
      revealed the greatest areas under the ROC curve (AUCs) for hip fracture (0.92 to
      0.93) in comparison to smaller AUCs for vertebral fractures (ranging from 0.84 to
      0.87), and the smallest AUCs for wrist and other fractures (ranging from 0.72 to
      0.77 and 0.72 to 0.78, respectively). Generally, the SOS measurement presented
      greater odds ratio (OR) than BUA and SI: 4.1 (3.09 to 5.43) for any fracture,
      11.66 (3.09 to 43.96) for hip fracture, 6.51 (3.61 to 11.73) for vertebral
      fracture, 3.32 (2.41 to 4.58) for wrist fracture and 4.2 (2.7 to 6.54) for other
      fracture. The present study demonstrates the ability of calcaneal QUS to
      discriminate between healthy individuals and subjects with different types of
      nontraumatic fractures. Calcaneal US parameters show the best sensitivity and
      specificity in discriminating the hip fracture patients from the controls.
      Generally, the SOS parameter is a better discriminator than SI and BUA and
      estimates the highest OR for fractures.

PMID- 12498946
TI  - Doppler ultrasound tracking instrument for monitoring blood flow velocity.
AB  - Doppler ultrasound (US) is potentially a valuable method for monitoring changes
      of blood flow velocity over a period of many minutes or even hours, but is seldom
      used in this way. One difficulty that may have contributed to this is the problem
      of maintaining a fixed geometry between the US beam and the blood vessel. A
      method of improving the success of monitoring might be to actively steer the US
      beam so as to maintain an adequate signal even when small displacements of the
      transducer occur. We have designed and built a prototype system for this purpose.
      The system comprises a continuous-wave phased-array transducer controlled by a
      purpose-built Doppler unit. The system constantly evaluates the quality of the
      returning Doppler signal in terms of total power and signal-to-noise ratio (SNR)
      (evaluated by assessing the quality of derived envelope signals), and steers the
      ultrasonic beam in a manner so as to improve the signal, should this be
      necessary. The system was tested in vitro, where the automatic tracking of the
      Doppler signal doubled the effective beam width of the transducer. Further
      developments that increase sensitivity and steering range should result in US
      Doppler systems that are better suited to long-term monitoring.

PMID- 12498947
TI  - Experimental evaluation of indicators of nonlinearity for use in ultrasound
      transducer characterizations.
AB  - Because the number of applications for medical ultrasonic devices continue to
      increase and, hence, the number of diagnostic ultrasound (US) systems increase,
      there is a need to reliably characterize the sources in terms of their output
      pressures. Currently, the transducers are characterized by making pressure
      measurements in water for every voltage range applied to the source and, then,
      linearly derate the measured pressure values to estimate the derated acoustic
      pressure levels. The process is time-consuming and inaccuracies are introduced in
      the derating process due to nonlinear effects. Therefore, there is a need to find
      an indicator of nonlinearity that could classify the measured pressure waveform
      as either linear, where the derating procedure would yield an accurate derated
      acoustic pressure estimate, or nonlinear, where the derating process would fail.
      Eight different indicators of nonlinearity were evaluated experimentally using
      spherically focused US transducers. The transducers were selected to test the
      indicator sensitivity to frequency (3 to 8 MHz), f-number (1 and 2), and
      transducer diameter (1.905 and 5.08 cm). Sensitivity to drive voltage conditions
      was also tested by exciting one of the transducers with pulses of different
      duration and phase. None of the eight nonlinearity indicators yielded consistent
      results. The lack of consistency resulted from the competing effects of nonlinear
      absorption and asymmetrical distortion, which have yet to be combined into a
      unified theory.

PMID- 12498948
TI  - The effects of digitization on the elastographic signal-to-noise ratio.
AB  - In elastography, the tissue under investigation is compressed and the resulting
      strain is estimated from the gradient of the displacement (time-delay) estimates.
      The displacements are typically estimated by cross-correlating the radiofrequency
      (RF) ultrasound signals of the pre- and postcompressed tissue. One of the
      parameters used to quantify the resulting quality of the elastogram is the
      elastographic signal-to-noise ratio (SNR(e)). For a uniformly elastic target (a
      single elastic modulus), the dependence of the SNR(e) on the applied strain has a
      bandpass characteristic that has been termed the strain filter. Theoretical
      expressions for the upper bound on the strain filter were developed earlier. Yet,
      simulated as well as experimental strain filters derived from uniformly elastic
      phantoms deviate from these upper bounds. The failure to achieve the upper bounds
      could be partially attributed to the fact that, in both simulations and
      experiments, the RF signals used to compute the TDEs are sampled and quantized.
      Using simulated models of uniformly elastic phantoms, a study of the dependence
      of the strain filter on the quantization and sampling rates was performed. The
      results indicated that the strain filter improves with both the sampling rate and
      the quantization, as expected. A theoretical analysis was done to incorporate
      quantization as a derating factor to the strain filter.

PMID- 12498949
TI  - Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in
      anesthetized rats.
AB  - The generation of ultrasound (US) bioeffects using a clinical imaging system is
      controversial. We tested the hypothesis that the presence of microbubbles in the
      US field of a medical imager induces biologic effects. Both kidneys of
      anesthetized rats were insonified for 5 min using a medical imaging system after
      the administration of microbubbles. One kidney was insonified using a continuous
      mode (30 Hz) and the opposite kidney was insonified using an intermittent (1 Hz)
      technique. The microbubbles were exposed to three different transducer
      frequencies and four transducer output powers. After insonification, the animals
      were euthanized, the kidneys were removed and their gross appearance scored under
      "blinded" conditions using a defined scale. After the administration of
      microbubbles, US imaging of the kidney caused hemorrhage in the renal tissue. The
      severity and area of hemorrhage increased with an increase in the transducer
      power and a decrease in the transducer frequency. Intermittent insonification in
      the presence of microbubbles produced a greater degree of renal hemorrhage than
      continuous imaging techniques.

PMID- 12498950
TI  - The influence of pulsed low-intensity ultrasound on matrix production of
      chondrocytes at different stages of differentiation: an explant study.
AB  - The proximal and distal parts of sterna of chick embryos represent cartilage
      undergoing endochondral ossification and hyaline cartilage, respectively.
      Cartilage explants from both regions were exposed for 20 min to pulsed low
      intensity ultrasound (PLIUS) with an intensity of 30 mW. cm(-2) (spatial average
      temporal average) at a frequency of 1.5 MHz, with a pulse burst frequency of 1
      kHz and burst duration of 200 micros. Histological and immunohistochemical
      analysis was performed on days 1, 3, 5 and 7 after treatment. An anabolic effect
      of PLIUS on matrix production was shown by an increase of up to 10% to 20% in
      quantitative immunohistochemical staining for type II collagen and aggrecan in
      the two parts of the sternum. PLIUS also increased type X collagen staining by up
      to 10% in certain regions of the proximal part of the sternum. Staining for type
      X collagen was negative in the distal part of the sternum in both PLIUS and
      control groups. These results suggest that PLIUS may stimulate bone formation by
      increasing hypertrophy of chondrocytes directed to terminal differentiation.
      However, PLIUS did not induce hypertrophy in hyaline cartilage; moreover,
      increased matrix synthesis indicates a potential role in cartilage repair.

PMID- 12498951
TI  - Prolongation of TCD-enhanced Doppler signal by continuous infusion of levovist.
AB  - This study evaluated the effects of two different rates of infusion of echo
      contrast agents (ECA) on signal enhancement. A total of 15 patients with
      insufficient Doppler signal due to inadequate transtemporal acoustic bone window
      were examined. Signal from the middle cerebral artery was recorded during the IV
      infusion of Levovist (300 mg/mL). Increment of signal enhancement in dB, time to
      signal enhancement appearance, time to clinically useful signal enhancement
      appearance, and duration of clinically useful signal enhancement were assessed
      during two infusions at the rate of 1 and 0.66 mL/min, respectively. Increment of
      signal enhancement was similar at the rate of 1 and 0.66 mL/min (p = 0.4). Mean
      time to signal enhancement appearance and mean time to clinically useful signal
      enhancement appearance were not significantly different with the two rates of
      infusion (p = 0.9 and p = 0.3, respectively). Mean duration of clinically useful
      signal enhancement was significantly higher with the infusion rate of 0.66 mL/min
      as compared to 1 mL/min (p < 0.0001). Levovist injected at the infusion rate of
      0.66 mL/min prolonged the mean duration of signal enhancement, maintaining its
      effectiveness.

PMID- 12498952
TI  - The effect of speed of sound in ultrasound test objects on lateral resolution.
AB  - Urethane test objects are available that are more durable than traditional gel
      based objects. Their ultrasound (US) propagation speed differs from scanner
      calibration velocity. This is clearly a disadvantage in checking caliper
      accuracy, but its effect on other measurements such as resolution is not well
      known. A test object containing a column of nylon filaments was constructed and
      filled with water at different temperatures to give US speeds of 1,540 m s(-1)
      and 1,450 m s(-1). Images of the filaments were digitally captured and analysed
      to obtain the full-width half-maximum of the target images at each depth. Target
      image width was greater at 1,450 m s(-1). Measurements were also performed for
      the two types of tissue-mimicking test objects; results were in close agreement
      with the water test object. US beam profiles are broader in media with low
      propagation velocities.

PMID- 12498953
TI  - The effect of pulsed ultrasound exposure on the oxygen dissociation curve of
      human erythrocytes in in vitro conditions.
AB  - The P(50) value, a marker for the behavior of the oxygen dissociation curve (ODC)
      and values of 2,3-diphosphoglyceric acid (2,3-DPG), blood gases and acid base
      parameters (pH, PCO(2), actual HCO(3)(-), base excess, PO(2), SO(2)) and
      erythrocyte parameters (the number of erythrocyte, hematocrit and hemoglobin
      values) that are known to effect P(50), were measured before and after ultrasound
      (US) exposure to examine the effect of pulsed US beams on the ODC of human
      erythrocytes. Venous blood samples taken from healthy subjects were sonicated at
      0 degrees C for 30 min by pulsed US beams with a constant frequency of 5 MHz.
      Experiments showed that the values of pH, actual HCO(3)(-), standard HCO(3)(-),
      base excess, 2,3-DPG and P(50) were changed considerably by pulsed US.
      Furthermore, correlation calculations were made to find out the relation between
      the P(50) values and the other parameters. As a result, a significant relation
      was found between P(50) values and the values of pH, actual HCO(3)(-), PO(2),
      SO(2) and 2,3-DPG. In conclusion, we can express that a highly significant
      increase occurs in P(50) value of venous blood after a pulsed US exposure at a
      constant frequency of 5 MHz for 30 min under in vitro conditions at 0(0)C. That
      is hemoglobin becomes suitable for deoxy (tense structure) conformation when
      blood affinity of O(2) is low. It means that hemoglobin becomes convenient for
      proton (H(+)) and CO(2) binding.

PMID- 12498954
TI  - Staging of brain pathology related to sporadic Parkinson's disease.
AB  - Sporadic Parkinson's disease involves multiple neuronal systems and results from
      changes developing in a few susceptible types of nerve cells. Essential for
      neuropathological diagnosis are alpha-synuclein-immunopositive Lewy neurites and
      Lewy bodies. The pathological process targets specific induction sites: lesions
      initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal
      nerves and anterior olfactory nucleus. Thereafter, less vulnerable nuclear grays
      and cortical areas gradually become affected. The disease process in the brain
      stem pursues an ascending course with little interindividual variation. The
      pathology in the anterior olfactory nucleus makes fewer incursions into related
      areas than that developing in the brain stem. Cortical involvement ensues,
      beginning with the anteromedial temporal mesocortex. From there, the neocortex
      succumbs, commencing with high order sensory association and prefrontal areas.
      First order sensory association/premotor areas and primary sensory/motor fields
      then follow suit. This study traces the course of the pathology in incidental and
      symptomatic Parkinson cases proposing a staging procedure based upon the readily
      recognizable topographical extent of the lesions.

PMID- 12498955
TI  - The vascular lesions in vascular and mixed dementia: the weight of functional
      neuroanatomy.
AB  - Vascular dementia appears rarer than previously thought, but the contribution of
      vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected
      patients (mixed dementias) is now recognized as frequent. The role of strategic
      areas of the brain involved in the cognitive decline induced by vascular lesions
      and their relative contributions to the severity of the dementing process remain
      poorly understood. We determined the relationship between the severity of
      clinical dementia and the volume of different brain areas affected by infarcts in
      a prospective clinicopathological study in elderly patients. A volumetric study
      of the functional zones of Mesulam's human brain map affected by vascular lesions
      was made and correlations between quantified neuropathological data and the
      severity of dementia were performed in cases with large vascular lesions only,
      pure AD, and both lesions. The severity of cognitive impairment was significantly
      correlated with the total volume of infarcts but in a multi-variate model the
      volume destroyed in the limbic and heteromodal association areas, including the
      frontal cortex and in the white matter explained 50% of the variability in MMSE
      and GDS. The total volume of ischemic lesions explained only 0.1-5% of the
      variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study
      confirms that infarcts located in strategic areas have a role in the mechanism of
      cognitive impairment and brings a key for their quantification. It may be useful
      for developing neuropathological criteria in multi-infarct and mixed dementias.

PMID- 12498956
TI  - A voxel-based morphometry study of temporal lobe gray matter reductions in
      Alzheimer's disease.
AB  - Several MRI studies have reported reductions in temporal lobe volumes in
      Alzheimer's disease (AD). Measures have been usually obtained with regions-of
      interest (ROI) drawn manually on selected medial and lateral portions of the
      temporal lobes, with variable choices of anatomical borders across different
      studies. We used the fully automated voxel-based morphometry (VBM) approach to
      investigate gray matter abnormalities over the entire extension of the temporal
      lobe in 14 AD patients (MMSE 14-25) and 14 healthy controls. Foci of
      significantly reduced gray matter volume in AD patients were detected in both
      medial and lateral temporal regions, most significantly in the right and left
      posterior parahippocampal gyri and the left posterior inferior temporal
      gyrus/fusiform gyrus (P<0.05, corrected for multiple comparisons). At a more
      flexible statistical threshold (P<0.001, uncorrected for multiple comparisons),
      circumscribed foci of significant gray matter reduction were also detected in the
      right amygdala/enthorinal cortex, the anterior and posterior borders of the
      superior temporal gyrus bilaterally, and the anterior portion of the left middle
      temporal gyrus. These VBM results confirm previous findings of temporal lobe
      atrophic changes in AD, and suggest that these abnormalities may be confined to
      specific sites within that lobe, rather than showing a widespread distribution.

PMID- 12498957
TI  - DHA-enriched phospholipid diets modulate age-related alterations in rat
      hippocampus.
AB  - Our previous work on rat hippocampus showed that a loss of docosahexaenoic acid
      (DHA) occurs in the fatty acid composition of phosphatidylethanolamine (PE),
      plasmenylethanolamine (PmE) and phosphatidylserine (PS) with increasing age. The
      present study investigated whether a DHA-enriched phospholipid dietary supplement
      could restore DHA levels and cholinergic activity. Male rats were fed a balanced
      diet containing both linoleic and alpha-linolenic acids until the age of 2, 18
      and 21 months. From 18 to 21 months, one subgroup received a diet supplemented
      with DHA-enriched phospholipids from egg yolk (E-PL), and another a diet with DHA
      enriched phospholipids from pig brain (B-PL). Compared to the control diet, the E
      PL diet restored the proportion of polyunsaturated fatty acids (PUFAs: 22:6n-3
      and 20:4n-6) in PE and PmE, while enhancing spontaneous and evoked-acetylcholine
      (Ach) release. The B-PL diet had no effect on PUFAs, but increased basal
      extracellular levels of Ach in 21-month-old rats as compared to the age-matched
      control. Our results show that supplementation with DHA-enriched egg PL can
      enhance Ach release and correct PUFA composition.

PMID- 12498958
TI  - Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha
      synuclein A30P transgenic mice.
AB  - Alpha-synuclein is a major component of Lewy bodies (LBs) in the substantia nigra
      and cortex in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and
      in glial inclusions in multiple systems atrophy (MSA). Mutations in alpha
      synuclein have been associated with autosomal dominant forms of PD. We
      investigated the clinical and neuropathological effects of overexpression of
      human alpha-synuclein, alpha-synuclein A30P, and alpha-synuclein A53T under the
      control of the hamster prion protein (PrP) promoter; 5-15x endogenous levels of
      protein expression were achieved with widespread neuronal, including nigral,
      transgene expression. High expression of alpha-synuclein A30P in the Tg5093 line
      was associated with a progressive motor disorder with rigidity, dystonia, gait
      impairment, and tremor. Histological analysis of this line showed aberrant
      expression of the protein in cell soma and progressive CNS gliosis, but no
      discrete Lewy body-like alpha-synuclein inclusions could be identified.
      Biochemical analysis demonstrated alpha-synuclein fragmentation. Despite strong
      expression of the transgene in the nigra, there was no specific deterioration of
      the nigrostriatal dopaminergic system as assessed by quantitation of nigral
      tyrosine hydroxylase (TH) containing neurons, striatal TH immunoreactivity,
      dopamine levels, or dopamine receptor number and function. Lower expressing lines
      had no specific behavioral or histopathological phenotype. Thus, high expression
      of mutant human alpha-synuclein resulted in a progressive motor and widespread
      CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line.

PMID- 12498959
TI  - Aged Fischer 344 rats exhibit altered orolingual motor function: relationships
      with nigrostriatal neurochemical measures.
AB  - The present study utilized a novel behavioral preparation to measure differences
      in orolingual motor function between young (6 months) and aged (24 months)
      Fischer 344 (F344) rats. Rats were trained to lick an isometric force-sensing
      operandum for water reinforcement so that the number of licks per session,
      licking rhythm and lick force could be compared between the two groups. The aged
      rats exhibited a greater number of licks per session, but a slowed licking
      rhythm, compared to the young rats. Lick force did not differ significantly
      between the groups. The dopamine (DA) uptake inhibitor nomifensine decreased all
      three measures in both groups. Analyses of whole brain tissue content of DA, 3,4
      dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the substantia
      nigra and dorsal striatum revealed no significant differences between the two age
      groups. Differences were observed between the two groups with respect to
      relationships between behavioral and neurochemical tissue measures. Striatal DA
      content and the number of licks per session were positively correlated for the
      young rats but not for the aged rats. In the aged rats, but not the young rats,
      positive correlations were also observed between licking rhythm and the
      DOPAC+HVA/DA ratio in the substantia nigra. These findings suggest that age
      related alterations in orolingual motor function may relate in part to functional
      changes in DA neuronal circuits.

PMID- 12498960
TI  - Age-related changes in theta frequency stimulation-induced long-term
      potentiation.
AB  - Several signaling mechanisms that are crucial for the induction of long-term
      potentiation (LTP) by theta frequency (5 Hz) trains of synaptic stimulation are
      altered in aged animals. To determine whether theta frequency stimulation-induced
      LTP is particularly sensitive to changes in synaptic function that occur in aged
      animals, we examined whether activating synapses in the hippocampal CA1 region
      with three different trains of theta pulse stimulation (TPS) has different
      effects on synaptic strength in hippocampal slices from aged and young mice. Our
      results indicate that TPS-induced LTP is not diminished in the aged hippocampus
      but does show a dependence on L-type voltage-sensitive calcium channels that is
      not seen in young animals. Moreover, we found that the facilitation of TPS
      induced LTP by co-activation of beta-adrenergic and cholinergic receptors is
      strongly reduced in slices from aged animals. Together, these results suggest
      that memory impairments in aged animals might arise, at least in part, from
      deficits in the ability of modulatory transmitters to regulate activity-dependent
      forms of synaptic plasticity.

PMID- 12498961
TI  - NMDA receptor antagonist treatment increases the production of new neurons in the
      aged rat hippocampus.
AB  - The production of new neurons declines during adulthood and persists, although at
      very low levels, in the aged hippocampus. Since neurogenesis in young adults has
      been related to learning and memory, its reduction may contribute to the age
      related impairments in these abilities. Adrenalectomy (ADX) enhances neurogenesis
      in the aged hippocampus, although it also induces neuronal cell death. Since the
      administration of an NMDA receptor antagonist enhances neurogenesis in young
      adult rats without deleterious morphological effects, we have tested whether
      neurogenesis could be reactivated in aged rats. Our study shows that cell
      proliferation, cell death, neurogenesis and the number of radial glia-like nestin
      immunoreactive cells decrease in middle-age (10 months) and remain very low in
      the aged hippocampus. Injection of the NMDA receptor antagonist to aged rats
      increases significantly the number of proliferating cells, new neurons and radial
      glia-like cells in the hippocampus.

PMID- 12498962
TI  - Age-related differences in brain activation during emotional face processing.
AB  - Advancing age is associated with significant declines on neurobehavioral tasks
      that demand substantial mental effort. Functional imaging studies of mental
      abilities indicate that older adults faced with cognitive challenges tend to
      activate more regions, particularly frontal, than their younger counterparts, and
      that this recruitment of additional regions may reflect an attempt to compensate
      for inefficiency in cortical networks. The neural basis of emotion processing in
      aging has received little attention, and the goal of the present study was to use
      functional magnetic resonance imaging (fMRI) to examine the influence of age on
      facial emotion processing and activation in cortical and limbic regions.
      Participants (eight old and eight young adults) viewed facial displays of
      happiness, sadness, anger, fear, disgust, and neutrality in alternating blocks of
      emotion and age discrimination. We predicted that in response to an emotion
      discrimination task, older adults would demonstrate increased use of frontal
      regions relative to younger adults, perhaps combined with diminished use of
      regions recruited by younger adults, such as temporo-limbic regions. During the
      emotion discrimination task, young participants activated, visual, frontal and
      limbic regions, whereas older participants activated parietal, temporal and
      frontal regions. A direct comparison between emotion and age discrimination
      revealed that while younger adults activated the amygdala and surrounding temporo
      limbic regions, older adults activated left frontal regions. The results of this
      study suggest that older adults may rely on different cortical networks to
      perceive emotional facial expressions than do their younger counterparts.

PMID- 12498963
TI  - Place cell rigidity correlates with impaired spatial learning in aged rats.
AB  - In humans and in animals, some aged individuals are severely impaired in learning
      and memory capacity whereas others perform as well as young adults. In the
      present study, the spatial memory capacity of young and aged rats was
      characterized by the Morris water maze task, and then firing patterns of
      hippocampal "place cells" were assessed as the animals explored a familiar
      environment and a geometrically-altered version of the environment. Spatial
      representations of hippocampal cells in young and memory-intact aged rats changed
      upon exposure to the altered environment. In contrast, spatial representations of
      many cells in aged, memory-impaired rats were unaffected by the environmental
      alteration. Furthermore, combining all groups, the extent to which spatial
      representations distinguished the familiar and altered environments predicted
      learning capacity in the water maze. These findings suggest that a major
      component of memory impairment in aging may be the failure of the hippocampus to
      encode subtle differences in contextual information that differ across multiple
      experiences, such as the sequence of training trials in the water maze.

PMID- 12498964
TI  - Association between blood pressure levels over time and brain atrophy in the
      elderly.
AB  - The relation between blood pressure level and degree of global brain atrophy is
      equivocal. We evaluated past and present blood pressure levels and change in
      blood pressure over 20 years in relation to the degree of cortical atrophy on
      magnetic resonance imaging (MRI). In 1995-1996, we measured blood pressure and
      performed MRI in 1077 nondemented elderly (age 60-90 years). For 513 of these, we
      had information on a blood pressure level 20 years before. The degree of cortical
      atrophy was semi-quantitatively scored (range 0-15). In late life, a high (>/=90
      mmHg) and low (<65 mmHg) diastolic blood pressure were associated with more
      cortical atrophy than a diastolic blood pressure level between 65-74 mmHg
      (adjusted difference 0.60 units (95% confidence interval (CI), 0.18-1.02) and
      0.77 units (0.28-1.25), respectively). Persons whose diastolic blood pressure had
      declined more than 10 mmHg over 20 years had more cortical atrophy than those
      with stable blood pressure levels (adjusted difference 0.53 units, 0.05-1.02).
      Both high and declining diastolic blood pressure levels are associated with more
      global brain atrophy on MRI.

PMID- 12498965
TI  - Effects of Ca2+ antagonists on motor activity and the dopaminergic system in aged
      mice.
AB  - We investigated the effects of the Ca(2+) antagonist nilvadipine on the
      dopaminergic system and motor activity in aged mice, in comparison with an other
      Ca(2+) antagonist, amlodipine. Furthermore, we examined the close correlation
      between the dopaminergic system and motor activity during the aging process.
      Striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA) contents were measured in 2-, 4-, 8-, 18- and 36-week-old mice. Behavioral
      tests (pole and catalepsy test) were performed with 4- and 36-week-old mice.
      Nilvadipine or amlodipine was administered intraperitoneally twice a day for 3
      consecutive days to 30-36-week-old mice. The striatal dopamine, DOPAC and HVA
      contents were examined and behavioral tests were performed 1h after the last
      injection of each Ca(2+) antagonist. The dopamine, DOPAC and HVA contents in 2
      week-old mice were significantly decreased in the striatum, as compared with 4
      week-old animals. Thereafter, age-related increases in the dopamine, DOPAC and
      HVA contents were observed from 4 to 18 weeks old. However, in 36-week-old mice,
      the dopamine and DOPAC contents were reduced in the striatum, as compared with 18
      week-old animals. Age-related decreases in motor function between 5- and 36-week
      old mice were observed in both pole test and catalepsy tests. On the other hand,
      nilvalipine treatment produced a significant and dose-dependent increase in the
      striatal dopamine and DOPAC contents in 30-36-week-old mice. In contrast, no
      significant changes were observed in the striatal dopamine content in amlodipine
      treated mice, although this drug showed a significant and dose-dependent increase
      in the striatal DOPAC and HVA content. In our behavioral study, nilvadipine also
      showed a significant and dose-dependent inhibition against motor deficits in 30
      36-week-old mice. In contrast, amlodipine showed no significant effect on motor
      deficits in 30-36-week-old mice. The present study demonstrated that nilvadipine
      has a protective effect against the deficits in both the striatal dopaminergic
      system and motor activity in aged mice. Our study also suggested that the
      beneficial effect of nilvadipine against motor abnormalities may be mediated by a
      protective effect against the reduced activity of the dopaminergic system in aged
      mice. These results suggested that nilvadipine may offer a new approach for the
      treatment of hypobulia in aged humans.

PMID- 12498966
TI  - Immune reactive cells in senile plaques and cognitive decline in Alzheimer's
      disease.
AB  - We examined the associations of postmortem neocortical immunoreactivities for
      microglia, astrocytes, Abeta and Tau with cognitive changes in clinically
      characterized subjects with pathological diagnoses (CERAD classification) of
      definite AD (9), possible AD (15) and age-matched controls (11). By measuring the
      fractional area (FA) of immunoreactivity, we found that Abeta deposits appear
      early in the pathogenesis of Abeta, but cannot account for cognitive decline. We
      found a significant increases in FA for microglia in possible AD cases
      (nondemented) compared to controls (P<0.05) and in FA for astrocytes in definite
      AD (demented) compared to possible AD (P<0.01). Tau immunoreactivity was observed
      only in the neuropil of definite AD cases (P<0.001). The significant increase in
      microglia between controls and AD possible cases suggests that activation of
      microglia occurs in the early pathogenesis of AD, whereas the significant
      association between astrocytic reaction and dementia, suggests that these cells
      play a role in the late stage of the disease, when dementia develops. Tau
      immunoreactivity appears as the strongest morphological correlate of dementia.

PMID- 12498967
TI  - Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer's disease and
      vascular dementia.
AB  - Increasing evidence suggests an interaction of oxidative stress and the formation
      of advanced glycation end products (AGE) in the onset and progression of
      Alzheimer's disease. We studied levels of pentosidine and N(epsilon)
      (carboxymethyl)-lysine (CML) in serum and cerebrospinal fluid (CSF) of 15
      patients with probable Alzheimer's disease (AD), 20 patients with vascular
      dementia (VD), and 31 control subjects (14 matched for age, and 17 younger
      patients). AGE protein concentrations in CSF did not differ within controls when
      divided into two subgroups by age. We found significantly elevated levels of CML
      in CSF of AD patients and of pentosidine in CSF of patients suffering from
      vascular dementia when compared to controls. The concentrations of pentosidine
      and CML in serum apparently did not relate directly to CSF values, suggesting
      influence of extra-cerebral factors in serum samples. It is concluded that AGE
      proteins are differentially affected in these types of dementia, depending on the
      specific neuropathology. Furthermore, measurements of AGE products in vivo should
      rely on CSF rather than blood samples.

PMID- 12498968
TI  - Screening of two mutations at exon 3 of the apolipoprotein E gene (sites 28 and
      42) in a sample of patients with sporadic late-onset Alzheimer's disease.
AB  - The search for further variation at the APOE gene in a sample of patients with
      sporadic late-onset Alzheimer's disease (AD) and related controls revealed two
      different mutations in the exon 3 of the gene. One, the Leu28-->Pro, always found
      on an APOE e(*)4 allele, was present in five of the 94 patients and in 1 of the
      157 controls. The other, Thr42-->Ala, found on an e(*)3 allele, was observed in
      only one AD patient, who also carried the Leu28-->Pro, but in none of the
      controls. In the AD patient group the allele e(*)4(-), corresponding to Leu28-
      >Pro, showed a frequency of 0.027, compared with only 0.003 in the controls.
      Compared to E3/3 and E3/2 genotypes, the risk of developing AD associated with
      the genotypes carrying the e(*)4 allele, the well-established risk allele for AD
      onset, was observed to be high (OR=3.16; 95% CI=1.62-6.20; P=0.0009), but the
      risk associated with genotypes carrying the Leu28-->Pro mutation was higher still
      (OR=10.95; 95% CI=1.25-95.75; P=0.015). The higher risk associated with this
      mutation was assessed by meta-analysis carried out using the data of three
      patient groups from a previously published study Kamboh et al. and from our
      study. The results indicated that, compared with all the other APOE genotypes,
      those carrying the Leu28-->Pro mutation were at a substantially higher risk of
      developing AD (OR=4.25; 95% CI=1.21-14.97).

PMID- 12498969
TI  - Optical imaging reveals reduced seizure spread and propagation velocities in aged
      rat brain in vitro.
AB  - Old age is the most common time for patients to develop epileptic seizures, and
      due to their frequent unusual clinical presentation the diagnosis of epilepsy is
      often delayed in the elderly. It is as yet unknown if pronounced alterations in
      the plastic properties of aging nervous tissue contribute to these phenomena. We
      employed a non-lesional in vitro epilepsy model to study seizure susceptibility,
      spread pattern, and propagation velocities in combined hippocampal-entorhinal
      cortex slices of aged rats and controls using electrophysiological methods and
      imaging of intrinsic optical signals. In aged animals we saw a less extensive
      spread of seizure-like events into areas adjacent to the region of onset of
      activity and a decreased spread velocity in various anatomical regions. In
      addition, both the activity-dependent shrinkage of the extracellular space (ECS)
      volume and the extracellular K(+) concentration were significantly reduced
      compared to controls. The results of this study are consistent with the clinical
      observation that epileptic seizures in the elderly have a reduced tendency to
      spread. In addition, our data suggest that in the absence of structural lesions
      seizure susceptibility in the aging brain is not increased.

PMID- 12498970
TI  - TGFbeta1 enhances formation of cellular Abeta/apoE deposits in vascular myocytes.
AB  - Brain injury increases the risk of Alzheimer's disease (AD) through unknown
      mechanisms. We studied deposition of amyloid-beta protein (Abeta) in cells
      exposed to transforming growth factor beta1 (TGFbeta1), a cytokine that regulates
      cell metabolism during brain injury, and apolipoproteinE (apoE), the major lipid
      transporter in the brain. The studies were conducted by using brain vascular
      smooth muscle cells that are engaged in beta-amyloidosis in vivo and produce
      Abeta in cell culture. We found that cell treatment with TGFbeta1 together with
      apoE4 strongly increased the amount of cellular Abeta. The intracellular Abeta co
      localized with apoE but not with TGFbeta, similarly as in vascular beta-amyloid.
      Some cellular Abeta/apoE deposits increased in size and persisted in culture even
      after the TGFbeta1 and apoE4 were removed. The appearance of cellular deposits of
      Abeta was associated with increased production of the amyloid-beta precursor
      protein and cellular retention of its mature form. The results suggest that the
      concomitant presence of apoE and TGFbeta1 can trigger vascular beta-amyloidosis
      by inducing intracellular formation of stable Abeta/apoE deposits.

PMID- 12498971
TI  - Progressive age-related impairment of cognitive behavior in APP23 transgenic
      mice.
AB  - Transgenic APP23 mice expressing human APP(751) with the K670N/M671L mutation,
      were compared at ages 3, 18 or 25 months to non-transgenic littermates in passive
      avoidance and in a small and large Morris maze. The task in the smaller pool
      habituated their flight response to the platform. Impairments in passive
      avoidance and small pool performance in APP23 mice were clearly age-related. In
      the larger Morris maze APP23 mice at all ages were impaired in latency and
      distance swum before finding the platform. Identical performance of 18-month
      APP23 and controls in a visible platform condition indicates that the Morris maze
      performance deficit was not due to sensory, motor or motivational alterations. At
      age 3 months both groups initially unexpectedly avoided the visible platform,
      suggesting that in young mice neophobia may contribute significantly to
      performance in cognitive tests. In conclusion, APP23 mice exhibit both early
      behavioral impairment in the large Morris maze as well as impairments in passive
      avoidance and small pool performance that are marked only in old age.

PMID- 12498972
TI  - Intrastriatal infusions of methoctramine improve memory in cognitively impaired
      aged rats.
AB  - Alterations of striatal cholinergic markers may correlate with cognitive
      impairments in aged rats. M2 muscarinic receptors were found to be presynaptic
      inhibitory autoreceptors on striatal cholinergic interneurons. The effect of
      bilateral intrastriatal infusions of the M2 muscarinic receptor antagonist
      methoctramine was assessed, in cognitively impaired aged (24-26 months) Long
      Evans female rats, on memory performances in a water maze. Compared with vehicle
      infusions, methoctramine injected bilaterally (1 microg/side) in the dorsolateral
      striatum, significantly improved procedural memory performance while having no
      effect on spatial working memory. Our results suggest that, in cognitively
      impaired aged rats, the blockade of M2 muscarinic receptors in the dorsolateral
      striatum improves procedural memory probably by enhancing the release of
      acetylcholine.

PMID- 12498973
TI  - Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer's
      disease.
AB  - Inflammatory processes are considered important in the pathogenesis of
      Alzheimer's disease (AD). Intercellular adhesion molecule-1 (ICAM-1) is an
      important mediator of inflammatory response and immune cell activation, is
      expressed on cerebrovascular endothelium and neuritic plaques in brain of AD
      patients, and seems to be implicated in the process of neuro-degeneration. A
      common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In
      this case-control study, we evaluated the distribution of E/K alleles and
      genotypes of the ICAM-1 gene in 98 patients affected by sporadic AD and 115 age-
      and sex-matched controls. The frequency of the EE genotype was significantly
      higher in AD patients (P<0.01). Logistic regression analysis indicated that the
      presence of EE genotype significantly increased the risk of AD (odds ratio 3.01
      [1.1-8.0], P<0.05). This study shows for the first time an association between
      ICAM-1 E/K gene polymorphism and AD, suggesting that polymorphisms of the ICAM-1
      gene may be clinically important and confirming that inflammatory mechanisms may
      be crucial in the pathophysiology of neuro-degenerative diseases.

PMID- 12498974
TI  - Oxidative stress in viral and alcoholic hepatitis.
AB  - Liver damage ranges from acute hepatitis to hepatocellular carcinoma, through
      apoptosis, necrosis, inflammation, immune response, fibrosis, ischemia, altered
      gene expression and regeneration, all processes that involve hepatocyte, Kupffer,
      stellate, and endothelial cells. Reactive oxygen and nitrogen species (ROS, RNS)
      play a crucial role in the induction and in the progression of liver disease,
      independently from its etiology. They are involved in the transcription and
      activation of a large series of cytokines and growth factors that, in turn, can
      contribute to further production of ROS and RNS. The main sources of free
      radicals are represented by hepatocyte mitochondria and cytochrome p450 enzymes,
      by endotoxin-activated macrophages (Kupffer cells), and by neutrophils. The
      consequent alteration of cellular redox state is potentiated by the correlated
      decrease of antioxidant and energetic reserves. Indices of free radical-mediated
      damage, such as the increase of malondialdehyde, 4-hydroxynonenal, protein
      adducts, peroxynitrite, nitrotyrosine, etc., and/or decrease of glutathione,
      vitamin E, vitamin C, selenium, etc., have been documented in patients with viral
      or alcoholic liver disease. These markers may contribute to the monitoring the
      degree of liver damage, the response to antiviral therapies and to the design of
      new therapeutic strategies. In fact, increasing attention is now paid to a
      possible "redox gene therapy." By enhancing the antioxidant ability of
      hepatocytes, through transgene vectors, one could counteract
      oxidative/nitrosative stress and, in this way, contribute to blocking the
      progression of liver disease.

PMID- 12498975
TI  - Proteomic method detects oxidatively induced protein carbonyls in muscles of a
      diabetes model Otsuka Long-Evans Tokushima Fatty (OLETF) rat.
AB  - Oxidative stress is implicated in a broad variety of chronic and acute diseases,
      including such age-related diseases as diabetes. To understand at the protein
      level cellular damage caused by the stress, we developed a proteomic method, in
      which protein carbonyls were derivatized with biotin hydrazide followed by two
      dimensional gel electrophoresis. The method, being capable of analyzing high
      molecular-mass proteins as large as myosin heavy chains (molecular mass
      approximately 200 kDa), was applied to detecting protein carbonyls in muscles of
      a diabetes model Otsuka Long-Evans Tokushima Fatty (OLETF) rat and a control Long
      Evans Tokushima Otsuka (LETO) rat. A number of proteins, including mitochondrial
      ATP synthase beta-chain, desmin, actin, and myosin, were found carbonylated. Our
      method would provide a means toward clarifying a comprehensive view of oxidative
      modifications of proteins during a long progression of age-related diseases and
      understanding the mechanism of the onset, progression, and complication of the
      diseases.

PMID- 12498976
TI  - Reversible S-glutathionylation of Cys 374 regulates actin filament formation by
      inducing structural changes in the actin molecule.
AB  - S-glutathionylation, the reversible formation of mixed disulphides of cysteinyl
      residues in target proteins with glutathione, occurs under conditions of
      oxidative stress; this could be a posttranslational mechanism through which
      protein function is regulated by the cellular redox status. A novel physiological
      relevance of actin polymerization regulated by glutathionylation of Cys(374) has
      been recently suggested. In the present study we showed that glutathionylated
      actin (GS-actin) has a decreased capacity to polymerize compared to native actin,
      filament elongation being the polymerization step actually inhibited. Actin
      polymerizability recovers completely after dethiolation, indicating that S
      glutathionylation does not induce any protein denaturation and is therefore a
      reversible oxidative modification. The increased exposure of hydrophobic regions
      of protein surface observed upon S-glutathionylation indicates changes in actin
      conformation. Structural alterations are confirmed by the increased rate of ATP
      exchange as well as by the decreased susceptibility to proteolysis of the
      subtilisin cleavage site between Met(47) and Gly(48), in the DNase-I-binding loop
      of the actin subdomain 2. Structural changes in the surface loop 39-51 induced by
      S-glutathionylation could influence actin polymerization in view of the
      involvement of the N-terminal portion of this loop in intermonomer interactions,
      as predicted by the atomic models of F-actin.

PMID- 12498977
TI  - Nitroxyl affords thiol-sensitive myocardial protective effects akin to early
      preconditioning.
AB  - Nitric oxide (NO) donors mimic the early phase of ischemic preconditioning (IPC).
      The effects of nitroxyl (HNO/NO(-)), the one-electron reduction product of NO, on
      ischemia/reperfusion (I/R) injury are unknown. Here we investigated whether
      HNO/NO(-), produced by decomposition of Angeli's salt (AS; Na(2)N(2)O(3)), has a
      cardioprotective effect in isolated perfused rat hearts. Effects were examined
      after intracoronary perfusion (19 min) of either AS (1 microM), the NO donor
      diethylamine/NO (DEA/NO, 0.5 microM), vehicle (100 nM NaOH) or buffer, followed
      by global ischemia (30 min) and reperfusion (30 min or 120 min in a subset of
      hearts). IPC was induced by three cycles of 3 min ischemia followed by 10 min
      reperfusion prior to I/R. The extent of I/R injury under each intervention was
      assessed by changes in myocardial contractility as well as lactate dehydrogenase
      (LDH) release and infarct size. Postischemic contractility, as indexed by
      developed pressure and dP/dt(max), was similarly improved with IPC and pre
      exposure to AS, as opposed to control or DEA/NO-treated hearts. Infarct size and
      LDH release were also significantly reduced in IPC and AS groups, whereas DEA/NO
      was less effective in limiting necrosis. Co-infusion in the triggering phase of
      AS and the nitroxyl scavenger, N-acetyl-L-cysteine (4 mM) completely reversed the
      beneficial effects of AS, both at 30 and 120 min reperfusion. Our data show that
      HNO/NO(-) affords myocardial protection to a degree similar to IPC and greater
      than NO, suggesting that reactive nitrogen oxide species are not only necessary
      but also sufficient to trigger myocardial protection against reperfusion through
      species-dependent, pro-oxidative, and/or nitrosative stress-related mechanisms.

PMID- 12498978
TI  - Cell-mediated reduction of protein and peptide hydroperoxides to reactive free
      radicals.
AB  - Radical attack on proteins in the presence of O(2) gives protein hydroperoxides
      in high yields. These peroxides are decomposed by transition metal ions, reducing
      agents, UV light and heat, with the formation of a range of reactive radicals
      that are capable of initiating further damage. Evidence has been presented for
      the formation of alcohols as stable products of peroxide decomposition, and these
      have been employed as markers of oxidative damage in vivo. The mechanism of
      formation of these alcohols is unclear, with both radical and nonradical pathways
      capable of generating these products. In this study we have investigated the
      reduction of peptide and protein hydroperoxides by THP-1 (human monocyte-like)
      cells and it is shown that this process is accompanied by radical formation as
      detected by EPR spin trapping. The radicals detected, which are similar to those
      detected from metal-ion catalyzed reduction, are generated externally to the
      cell. In the absence of cells, or with cell-conditioned media or cell lysates,
      lower concentrations of radicals were detected, indicating that intact cells are
      required for rapid hydroperoxide decomposition. The rate of radical generation
      was enhanced by preloading the cells with ascorbate, and this was accompanied by
      intracellular formation of the ascorbate radical. It is proposed that
      decomposition of some amino acid and peptide hydroperoxides occurs
      extracellularly via the involvement of a cell-surface reducing system, such as a
      trans-plasma membrane electron transport system (TPMET) either directly, or
      indirectly via redox cycling of trace transition metal ions.

PMID- 12498979
TI  - Antioxidant ebselen reduces oxidative damage in focal cerebral ischemia.
AB  - The antioxidant and neuroprotective potential of the glutathione peroxidase mimic
      ebselen has been investigated in experimental stroke. Intravenous ebselen (1
      mg/kg/h) or vehicle infusion was started 45 min before permanent middle cerebral
      artery occlusion in the rat, and continued until the end of the experiment. The
      topography and extent of oxidative damage to the brain was assessed
      immunohistochemically using an antibody for DNA damage that identified
      hydroxylated products of 2'-deoxyguanosine (8-OHdG/8-oxodGuo) and an antibody for
      lipid peroxidation that identified the 4-hydroxynonenal histidine adduct (4-HNE).
      Ischemic damage was mapped and evaluated with standard histopathology. In the
      vehicle-treated rats immunopositive staining for both 8-oxodGuo and 4-HNE
      extended beyond the boundary of ischemic damage. In ebselen-treated rats, the
      extent of tissue immunopositive for 8-oxodGuo, and 4-HNE was less than that
      demonstrating ischemic damage confirming the antioxidant mechanism of action in
      vivo. In addition, ebselen treatment induced a 28% reduction in cortical ischemic
      damage (p <.02).

PMID- 12498980
TI  - Spinal cord injury increases iron levels: catalytic production of hydroxyl
      radicals.
AB  - This study used a weight drop impact injury model to explore the role of iron and
      the reality of iron-catalyzed hydroxyl radical ((*)OH) formation in secondary
      spinal cord injury (SCI). The time course of total extracellular iron was
      measured following SCI by microcannula sampling and atomic absorption
      spectrophotometry analysis. Immediately following SCI, the total iron
      concentration increased from an undetectable level to an average of 1.32 microM.
      The time course of SCI-induced (*)OH-generating catalytic activity in the cord
      was obtained by determining the ability of tissue homogenate to convert hydrogen
      peroxide to (*)OH and then measuring 2,3-dihydroxybenzoic acid, a hydroxylation
      product of salicylate. The concentration of 2,3-DHBA quickly and significantly
      increased (p <.001) and returned to sham level (p = 1) by 30 min post-SCI.
      Desferrioxamine (80 and 800 mg/kg body weight) significantly (p <.001) reduced
      the catalytic activity, suggesting that iron is the major contributor of the
      activity. Administering FeCl(3) (100 microM)/EDTA (0.5 mM) in ACSF into the cord
      through a dialysis fiber significantly increased SCI-induced (*)OH production in
      the extracellular space, demonstrating that Fe(3+) can catalyze (*)OH production
      in vivo. Our results support that iron-catalyzed (*)OH formation plays a role in
      the early stage of secondary SCI.

PMID- 12498981
TI  - Ethnic diversity in a critical gene responsible for glutathione synthesis.
AB  - The tripeptide glutathione is an important biomolecule that acts as a scavenger
      of free radicals and plays a role in a number of other cellular processes. A
      number of diseases, including Parkinson's disease, cancer, sickle cell anemia,
      and HIV infection, are thought to involve oxidative stress and depletion of
      glutathione. The heterodimeric enzyme glutamate cysteine ligase catalyzes the
      first, rate-limiting step in the de novo synthesis of glutathione. Functional
      polymorphisms within the gene encoding the subunits of glutamate cysteine ligase
      have the potential to affect the body's capacity to synthesize glutathione and
      thus, may affect those diseases in which oxidative stress and glutathione have
      roles. We undertook systematic screening for polymorphisms within the exons and
      intronic flanking sequences of the gene encoding the catalytic subunit of
      glutamate cysteine ligase (GCLC). We identified 11 polymorphisms in GCLC and
      established allele frequencies for those polymorphisms in a population fitting
      the demographics of the middle Tennessee area. The nonsynonymous polymorphism
      C1384T was found only in individuals of African descent. In addition, allele
      frequencies for three other polymorphisms differ between Caucasians and African
      Americans. Understanding these polymorphisms may lead to better understanding of
      diseases where glutathione is important so that better treatments may be
      developed.

PMID- 12498982
TI  - Melatonin does not "directly scavenge hydrogen peroxide": demise of another myth.
AB  - We have reexamined claims that melatonin directly scavenges hydrogen peroxide and
      shown them to be unfounded. Relative hydrogen peroxide concentrations were
      determined in the absence and presence of melatonin using both an isoluminol
      based chemiluminescence assay (with measurements at circa 40 s, 6 h, and 24 h
      after mixing) and the phenol red/horseradish peroxidase assay employed by two
      earlier groups of workers (with measurements at 5 s, then every minute for the
      first 5 min, and then every hour to 5 h). Both assay procedures were in
      agreement. There was no significant change in the hydrogen peroxide
      concentrations over 24 h, and, furthermore, the concentrations of H(2)O(2) in the
      presence and absence of melatonin were the same within experimental error. Our
      results were obtained in metal ion-free systems. It therefore appears likely that
      the claims for a direct melatonin/H(2)O(2) reaction were due to contamination by
      traces of transition metal ions.

PMID- 12498983
TI  - Flavan-3-ols and procyanidins protect liposomes against lipid oxidation and
      disruption of the bilayer structure.
AB  - The antioxidant activity and the membrane effects of the flavanols (-)
      epicatechin, (+)-catechin, and their related oligomers, the procyanidins, were
      evaluated in liposomes composed by phosphatidylcholine:phosphatidylserine (60:40,
      molar ratio). When liposomes were oxidized with a steady source of free radicals,
      the flavanols and procyanidins (25 microM monomer equivalents) inhibited
      oxidation in a manner that was related to procyanidin chain length. Flavanols and
      procyanidins did not influence membrane fluidity or lipid lateral phase
      separation. However, flavanols and procyanidins induced a decrease in the
      membrane surface potential and protected membranes from detergent-induced
      disruption. These effects were dependent on flavonoid concentration, procyanidin
      chain length, and membrane composition. Flavanol- and procyanidin-induced
      inhibition of lipid oxidation was correlated with their effect on membrane
      surface potential and integrity. These results indicate that the interaction of
      flavanols and procyanidins with phospholipid head groups, particularly with those
      containing hydroxyl groups, is associated with a reduced rate of membrane lipid
      oxidation. Thus, flavanols and procyanidins can potentially reduce oxidative
      modifications of membranes by restraining the access of oxidants to the bilayer
      and the propagation of lipid oxidation in the hydrophobic membrane matrix.

PMID- 12498984
TI  - A low molecular weight antioxidant decreases weight and lowers tumor incidence.
AB  - Stable free radical nitroxides are potent antioxidants possessing superoxide
      dismutase- and catalase-mimetic activity that protect cells and animals against a
      variety of oxidative insults. Tempol, as a representative nitroxide, was
      evaluated for its influence on weight maintenance and spontaneous tumor incidence
      in C3H mice. Tempol administered in either the drinking water or food did not
      show any untoward effects and prevented animals from becoming obese. Tempol
      treated animals' leptin levels were reduced. Long-term treatment with Tempol
      significantly decreased tumorigenesis when compared to controls (10 vs. 40%,
      respectively). Selected tissues from Tempol-treated animals exhibited elevated
      levels of mitochrondrial uncoupling protein-2 (UCP-2) and HSP70. The present data
      suggest that nitroxides upregulate UCP-2, obviate weight gain, and decrease age
      related spontaneous tumor incidence. As a class, nitroxides may provide overall
      health benefits by contributing to decreased obesity and tumor incidence.

PMID- 12498985
TI  - Vitamin C inhibits diethylmaleate-induced L-cystine transport in human vascular
      smooth muscle cells.
AB  - Adaptive increases in intracellular glutathione (GSH) in response to oxidative
      stress are mediated by induction of L-cystine uptake via the anionic amino acid
      transport system x(c)(-). The recently cloned transporter xCT forms a
      heteromultimeric complex with the heavy chain of 4F2 cell surface antigen
      (4F2hc/CD98). Depletion of GSH by the electrophile diethylmaleate (DEM) induces
      the activity and expression of xCT in peritoneal macrophages. We here examine the
      effects of vitamin C on induction of xCT by DEM in human umbilical artery smooth
      muscle cells. DEM caused time- (3-24 h) and concentration- (25-100 microM)
      dependent increases in L-cystine transport, with GSH depleted by 50% after 6 h
      and restored to basal values after 24 h. xCT mRNA levels increased after 4 h DEM
      treatment with negligible changes detected for 4F2hc mRNA. DEM caused a rapid (5
      30 min) phosphorylation of p38(MAPK). Inhibition of p38(MAPK) by SB203580 (10
      microM) enhanced DEM-induced increases in L-cystine transport and GSH, whereas
      inhibition of p42/p44(MAPK) (PD98059, 10 microM) had no effect. Pretreatment of
      cells with vitamin C (100 microM, 24 h) attenuated DEM-induced adaptive increases
      in L-cystine transport and GSH levels. Inhibition of p38(MAPK), but not
      p42/p44(MAPK), reduced the cytoprotective action of vitamin C. Our findings
      suggest that DEM induces activation of xCT via intracellular signaling pathways
      involving p38(MAPK), and that vitamin C, in addition to its antioxidant
      properties, may modulate this signaling pathway to protect smooth muscle cells
      from injury.

PMID- 12498986
TI  - Evidence for dopamine-derived hydroxyl radical formation in the nigrostriatal
      system in response to axotomy.
AB  - We have evaluated the ability of the injured nigrostriatal dopaminergic system to
      produce highly reactive hydroxyl radicals ((*)OH) by the electrochemical
      detection of salicylate hydroxylation. Unilateral transection of the medial
      forebrain bundle transiently increased the formation of (*)OH in substantia nigra
      (SN) but not in striatum during the first 48 h postlesion, when most relevant
      changes in terms of oxidatively modified proteins take place. Short-term adaptive
      axotomy-induced changes in substantia nigra included downregulation of nigral
      tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA expression and more
      intense TH immunoreactivity. Maintained inhibition of monoamine oxidase activity
      with deprenyl totally prevented the axotomy-induced formation of (*)OH, thus
      demonstrating the dopaminergic nature of these radicals. In contrast, deprenyl
      treatment, which is associated with a diminution in free radical production,
      failed to delay the onset of dopaminergic degeneration. This observation
      highlights the importance of being extremely cautious when analyzing parameters
      of oxidative stress and extrapolating them as a primary cause of cell death in
      the context of neurodegeneration. Long-term adaptive changes included a dramatic
      downregulation of DAT mRNA expression along with a moderate decrease in TH mRNA
      levels in SN. We anticipate a key regulatory role of the DAT to maximally
      optimize dopaminergic transmission in the synaptic cleft under conditions of
      degeneration.

PMID- 12498987
TI  - Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron.
AB  - In many models, a protective role for heme oxygenase-1 (HO-1), the rate-limiting
      enzyme in heme degradation, has been demonstrated. Also, HO-1 null mice (KO) are
      more susceptible to inflammation and hypoxia and transplant rejection.
      Nonetheless, their response to hyperoxia (> 95% O(2)) has not yet been evaluated.
      Surprisingly, after acute hyperoxic exposure, KO had significantly decreased
      markers of lung oxidative injury and survived chronic hyperoxia as well as wild
      type (WT) controls. Disrupted HO-1 expression was associated with decreased lung
      reactive iron and iron-associated proteins, decreased NADPH cytochrome cp450
      reductase activity, and decreased lung peroxidase activity compared to WT.
      Injection of tin protoporphyrin, an inhibitor of HO, in the WT decreased acute
      hyperoxic lung injury, whereas transduction of human HO-1 in the KO reversed the
      relative protection of the KO to acute injury and worsened hyperoxic survival.
      This suggests that disruption of HO-1 protects against hyperoxia by diminishing
      the generation of toxic reactive intermediates in the lung via iron and H(2)O(2).

PMID- 12498988
TI  - Retrograde signaling in the regulation of synaptic transmission: focus on
      endocannabinoids.
AB  - This review covers recent developments in the cellular neurophysiology of
      retrograde signaling in the mammalian central nervous system. Normally at a
      chemical synapse a neurotransmitter is released from the presynaptic element and
      diffuses to the postsynaptic element, where it binds to and activates receptors.
      In retrograde signaling a diffusible messenger is liberated from the postsynaptic
      element, and travels "backwards" across the synaptic cleft, where it activates
      receptors on the presynaptic cell. Receptors for retrograde messengers are
      usually located on or near the presynaptic nerve terminals, and their activation
      causes an alteration in synaptic transmitter release. Although often considered
      in the context of long-term synaptic plasticity, retrograde messengers have
      numerous roles on the short-term regulation of synaptic transmission. The focus
      of this review will be on a group of molecules from different chemical classes
      that appear to act as retrograde messengers. The evidence supporting their
      candidacy as retrograde messengers is considered and evaluated. Endocannabinoids
      have recently emerged as one of the most thoroughly investigated, and widely
      accepted, classes of retrograde messenger in the brain. The study of the
      endocannabinoids can therefore serve as a model for the investigation of other
      putative messengers, and most attention is devoted to a discussion of systems
      that use these new messenger molecules.

PMID- 12498989
TI  - Coexistence and function of different neurotransmitter transporters in the plasma
      membrane of CNS neurons.
AB  - Transporters able to recapture released neurotransmitters into neurons can no
      longer be considered as cell-specific neuronal markers. In fact, colocalization
      on one nerve terminal of transporters able to selectively recapture the released
      endogenously synthesized transmitter (homotransporters) and of transporters that
      can selectively take up transmitters/modulators originating from neighboring
      structures (heterotransporters) has been demonstrated to occur on several
      families of nerve terminals. Activation of heterotransporters often increases the
      release of the transmitter stored in the terminals on which the
      heterotransporters are localized. The release caused by heterotransporter
      activation takes place through multiple mechanisms including exocytosis, either
      dependent on external Ca(2+) or on Ca(2+) mobilized from intraterminal stores,
      and homotransporter reversal. Homocarrier-mediated release elicited by
      heterocarrier activation represents a clear case of transporter-transporter
      interaction. Although the functional significance of transporter coexpression on
      one nerve terminal remains to be established, it may in some instances reflect
      cotransmission. In other cases, heterotransporters may mediate modulation of
      basal transmitter release in addition to the modulation of the evoked release
      brought about by presynaptic heteroreceptors. Heterotransporters are also
      increasingly reported to exist on neuronal soma/dendrites. With the exception of
      EAAT4, the glutamate transporter/chloride channel situated on GABAergic Purkinje
      cells in the cerebellum, the functions of somatodendritic heterocarriers is not
      understood.

PMID- 12498990
TI  - Controversies in urinary iodine determinations.
AB  - Iodine deficiency (ID) is associated with increased prevalence of goiter,
      increased risk for neurodevelopmental disorders, and is the world's leading cause
      of intellectual deficits. Iodine nutritional status of a population is assessed
      by measurements of urinary iodine concentrations which are also used to define,
      indicate, survey and monitor iodine deficiency and consequently its treatment.
      Several methods are available for urinary iodine determination. Discussed here
      are some of the limitations and controversies related to urinary iodine
      determinations, and recent findings with emphasis on measurements of urinary
      iodine concentrations in children and during pregnancy.

PMID- 12498991
TI  - Optimized preparation of urine samples for two-dimensional electrophoresis and
      initial application to patient samples.
AB  - OBJECTIVE: We optimized of the preparation of urinary samples to obtain a
      comprehensive map of urinary proteins of healthy subjects and then compared this
      map with the ones obtained with patient samples to show that the pattern was
      specific of their kidney disease. DESIGN AND METHODS: The urinary protein
      excretion patterns of 49 healthy men and 4 patients with renal disease were
      obtained by 2D electrophoresis. Silver nitrate stained protein spots were
      identified by mass spectrometry. RESULTS: Reproductive 2D gels identified 5
      classes of proteins systematically found in healthy subjects, irrespective of
      age. The proteins evidenced included serum albumin and its specific proteolytic
      products, Tamm-Horsfall, transferrin, zinc-alpha2-glycoprotein, alpha1
      microglobulin, haptoglobin, and Ig light chains. CONCLUSIONS: This study of a
      large panel of healthy individual showed that 2D urinary pattern was constant
      over time and reveal for the first time the relative abundance of albumin
      fragments in healthy subjects' urine. The profiles of the 4 patients, were
      specific of their renal disease.

PMID- 12498992
TI  - A reverse transcription comparative real-time PCR method for quantitative
      detection of angiogenic growth factors in head and neck cancer patients.
AB  - OBJECTIVES: Head and neck cancer is one of the ten most frequent cancers in the
      world. The angiogenic growth factors VEGF, PDGF and bFGF play a role in cancer
      aggressiveness. We developed a sensitive method to quantify the gene expression
      of these factors in the tissues of head and neck cancer patients. DESIGN AND
      METHODS: All assays were performed using real-time RT-PCR, which yields a value
      (Ct) denoting the threshold cycle of PCR amplification at which product is first
      detected by fluorescence. The Ct is dependent on the quantity of the target
      molecule in the sample. To control for variation in RNA quantity and quality, we
      used 18S ribosome RNA as an internal control to calculate a relative Ct for the
      target molecules of interest, VEGF, PDGF and bFGF. A serially diluted positive
      control sample was analyzed by linear regression to determine the sensitivity and
      linearity of the assay. Paired normal and cancerous tissue samples from 115 head
      and neck cancer patients were assayed to ascertain the relative levels of the
      growth factors. RESULTS: The CVs of within-run and between-run assays for VEGF,
      PDGF and bFGF were all less than 3%. The correlation coefficient of the RNA
      concentrations and Ct values were 0.9987, 0.9977, and 0.9996 respectively for
      VEGF, PDGF and bFGF. The assay was sensitive to as little as 10(-3) ng of RNA.
      All three growth factors were significantly increased in tumor tissue as compared
      to normal tissue. VEGF, PDGF and bFGF levels were elevated in 71.3%, 58.2% and
      54.0% of cancerous tissue samples, with average levels of over-expression of
      35.1, 24.6 and 13. sixfold, respectively. CONCLUSION: This method provides
      sensitive, quantitative, high-throughput analysis for direct comparison of gene
      expression levels between samples, while adjusting for factors that may influence
      quantity determination. It should be applicable to molecules other than
      angiogenic growth factors, as well.

PMID- 12498993
TI  - Role of estrogen in the regulation of cholesteryl ester synthesis in macrophages:
      the interaction between native and modified low density lipoprotein and human
      monocyte-derived macrophages.
AB  - OBJECTIVES: To study the effects of estrogen on the changes in cholesterol
      esterification induced by native and modified low density lipoprotein (LDL) in
      macrophages. DESIGN AND METHODS: Human monocyte-derived macrophages (HMDM) were
      used, and the influence of the presence of 17beta estradiol in the short term,
      and during the maturation of the cells, on the esterification of cholesterol from
      native (nLDL), acetylated (acLDL) and oxidized (oxLDL) LDL was determined.
      RESULTS: In the short-term (6 h), 17beta estradiol (1.5 x 10(-6)M) did not affect
      the esterification of cholesterol from acLDL or oxLDL, but with native LDL (nLDL)
      a 1.5-fold increase was observed. In contrast, long-term exposure of HMDM during
      maturation to 17beta-estradiol (1.5 x 10(-9)M - 1.5 x 10(-5)M) decreased
      cholesterol esterification in the presence of oxLDL and acLDL, but not nLDL.
      CONCLUSIONS: These results suggest that both the time of exposure and the
      concentration of estrogen used influence its effects on the interaction between
      HMDM and LDL, and thus on macrophage foam cell formation.

PMID- 12498994
TI  - Evaluation of cytokeratin-19 & cytokeratin-20 and interleukin-6 in Egyptian
      bladder cancer patients.
AB  - OBJECTIVES: This study was designed to detect the expression of CK-19 and CK-20
      in tissue specimens and IL-6 in the sera (as a noninvasive maneuver) of bladder
      cancer patients. Results were correlated with the clinico-pathologic parameters,
      Bilharziasis and the occurrence of relapse of the carcinoma among Egyptian
      bladder cancer patients. METHODS: Subjects of this study were 50 cases of bladder
      carcinoma (19 cases were positive for Bilharziasis) as well as 20 cystitis cases
      as control (7 cases were positive for Bilharziasis). Messenger ribonucleic acid
      extracted from fresh frozen tissue specimens with bladder tumor and the control
      group were collected and subjected to RT-PCR to detect expression of the
      amplification bands of CK-19 and CK-20 (214 and 370 base pairs). In the mean
      time, Interleukin-6 was quantified in the sera of the patients using ELISA kit.
      RESULTS: CK-19 and CK-20 RNAs were expressed in bladder cancer cases, but not
      expressed in the control group. They were significantly correlated to advanced
      tumor stage and grade, while CK-19 positivity, was also, correlated to tumor
      recurrence and tumor pathology being more in SCC than TCC. Moreover, IL-6
      positivity was correlated to the occurrence of malignancy, advanced grade and
      pathology being more in SCC than TCC. ROC curve was utilized to choose the best
      cut-off for serum IL-6 (49.2 pg/mL). At the determined cut-off, the sensitivity
      was 66% and the specificity was 95%. Bilharziasis was found to be related to
      advanced stages and grades of bladder cancer. CONCLUSION: CK-19, CK-20 and IL-6
      were strongly associated with malignant phenotype of Egyptian bladder tissues, so
      they may be used as additional markers for assessment of bladder cancer patients.

PMID- 12498995
TI  - Reduced acetylcholinesterase activity in erythrocyte membranes from patients with
      phenylketonuria.
AB  - OBJECTIVE: a) To evaluate acetylcholinesterase (AChE) activities in erythrocyte
      membranes from phenylketonuric (PKU) patients and controls and to correlate with
      their plasma phenylalanine (Phe), tyrosine (Tyr), alanine (Ala) and dopamine (DA)
      levels. b) To determine the in vitro effects of Phe, Ala and Phe plus Ala on
      their AChE activities. DESIGN AND METHODS: AChE activities were determined
      spectrophotometrically in erythrocyte membranes from PKU children (n = 12)
      adhering to their diet (group A), from 11 "off diet" (group B) and from 23
      controls. Their plasma amino acids were evaluated with an amino acid analyser and
      DA with an HPLC method. Ala (1.8 mM) and/or Phe (1.8 mM) were added in the enzyme
      incubation medium from controls, whereas only Ala was added in that from group B.
      RESULTS: AChE activity (1.19 +/- 0.05 deltaOD/min x mg protein), Tyr (46 +/- 17
      micromol/L) and DA (56 +/- 18 micromol/L) were remarkably decreased by about 60%
      in group B as compared to those of group A (3.01 +/- 0.18 deltaOD/min x mg
      protein, 115 +/- 39 micromol/L, 137 +/- 29 micromol/L, respectively, p < 0.001)
      and controls (3.13 +/- 0.16 deltaOD/min x mg protein, 117 +/- 44 micromol/L, 142
      +/- 22 micromol/L, respectively, p < 0.001). Phe negatively correlated with AChE
      activity and positively with plasma Tyr and DA. Ala reversed the inhibited AChE
      by Phe in erythrocyte membranes from healthy children to control values, whereas
      no reverse effect was observed on the enzyme activity from PKU patients.
      CONCLUSIONS: a) The low levels of DA and its precursor Tyr are due to the high
      Phe blood levels, as a consequence of the decreased activity of Phe-hydroxylase
      in the liver of our patients. So, high Phe blood levels inhibit AChE in PKU
      patients, probably resulting in higher acetylcholine concentrations. b)
      Determination of AChE in erythrocyte membranes from PKU could be a useful marker
      for the neurotoxic effects of Phe.

PMID- 12498996
TI  - Circulating lipid peroxidation and antioxidant status in cervical cancer
      patients: a case-control study.
AB  - OBJECTIVES: The present case-control study was conducted to investigate the
      status of circulating lipid peroxidation and the enzymic and nonenzymic
      antioxidants of cervical cancer patients. DESIGN AND METHODS: Plasma
      thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and the
      levels of antioxidants such as reduced glutathione (GSH), glutathione peroxidase
      (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), vitamin C and
      vitamin E were estimated in circulation of thirty patients and an equal number of
      age matched normal subjects as control. RESULTS: Significantly elevated levels of
      plasma TBARS and CD and significantly lowered levels of GSH, GPx, GST, SOD
      vitamin C and vitamin E were observed in cervical cancer patients as compared to
      controls. Our study reveals increased lipid peroxidation and possible breakdown
      of antioxidant status in patients with cervical carcinoma. CONCLUSION: These
      results indicate that low levels of GSH, GPx, GST, SOD, vitamin E and vitamin C
      in the circulation of cervical cancer patients may be due to their increased
      utilization to scavenge lipid peroxides as well as their sequestration by tumor
      cells. Malnutrition may also be a significant cause for the increased prevalence
      of cervical cancer in women with a low socioeconomic status.

PMID- 12498997
TI  - Increased oxidative stress and hypozincemia in male obesity.
AB  - OBJECTIVES: Antioxidants protect an organism from the detrimental effects of free
      radicals via scavenging or inhibiting their formation. Alterations in the levels
      of antioxidants and several essential trace elements in the plasma and various
      tissues of ob/ob mice have been reported previously. The aim of this study was to
      investigate oxidative status and trace elements in obese individuals. DESIGN AND
      METHODS: Seventy-six obese men (body mass index (BMI) > 30 kg/m(2)) and 24
      healthy, age-matched male control volunteers were enrolled in the study. Fasting
      plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL
      levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide
      dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive
      substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu),
      zinc (Zn) and iron (Fe) levels were also measured. RESULTS: We found that the
      mean Cu and Fe levels in obese individuals were not significantly different than
      those in the control group, whereas the mean Zn levels were significantly lower
      than those of the control group (p = 0.023). The mean erythrocyte CuZn-SOD and
      GSH-Px levels in obese individuals were significantly lower than those in
      controls (p = 0.001) whereas erythrocyte TBARS levels were significantly higher
      (p = 0.001) than those of the control group. CONCLUSION: We conclude that male
      obesity is associated with defective antioxidant status and hypozincemia, which
      may have implications in the development of obesity related health problems.

PMID- 12498998
TI  - Effects of vitamin E supplementation on blood antioxidants levels in patients
      with Behcet's disease.
AB  - Behcet's disease (BD) is known for many years, yet its etiology remains unknown.
      In BD, the increased production of reactive oxygen species from activated
      neutrophils may reduce concentrations of antioxidant vitamins and enzymes in
      plasma and red blood cells (RBC). Vitamin E is an important fat soluble
      antioxidant and its role on antioxidant parameters of BD is unclear. The study
      was undertaken to evaluate the role of vitamin E on lipid peroxidation (MDA)
      levels, antioxidant vitamin and enzyme concentrations in plasma and RBC in
      patients with BD. There were three groups i.e., control, patient and treatment
      groups with twenty-five subjects in each. Nonsmoking patients with BD, patient
      group, was compared with an equal number of healthy control subjects (control
      group). Blood samples were taken from both control and patient groups and then
      oral vitamin E was daily supplemented to the patients with BD for six weeks
      (treated group). At the end of six weeks, blood was taken from the treated group
      once more. RBC and plasma MDA levels, serum neopterin, complement system (C(3)
      and C(4)), ASO, CRP, rheumatoid factor, plasma lipoprotein (a), total cholesterol
      concentrations and erythrocyte sedimentation rate were higher in the patient
      group than in the control group, but they were lower in the treatment group than
      in the patient group. While vitamins A, E and beta-carotene concentrations in
      plasma, catalase, glutathione peroxidase activities and reduced glutathione
      levels in RBC and plasma were lower in patient group than in the controls, they
      were found to be higher in the treatment group than in the patient group. These
      results provide some evidence for a potential role of increased lipid
      peroxidation and decreased enzymatic and non enzymatic antioxidants in BD by its
      inflammatory character and vitamin E which may strengthen the antioxidant defense
      system, and may contribute to the treatment of BD.

PMID- 12498999
TI  - Serum nitrates and vasoactive intestinal peptide in patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND: The normal esophageal motility is a balance between excitatory
      cholinergic "muscarinic" innervations and noncholinergic nonadrenergic inhibitory
      innervations. The latter is mediated by nitric oxide (NO) and/or vasoactive
      intestinal polypeptide (VIP). METHODS: The study included 50 patients with gastro
      esophageal reflux disease (GERD), and 10 healthy controls of matched age and sex.
      Patients were divided into five groups according to the degree of lower end
      esophagitis (Savary-Miller classification). Serum VIP was measured using enzyme
      immunoassay after peptide purification. Serum nitrate as an index of nitric oxide
      generation was determined biochemically. RESULTS: Serum nitrate and VIP levels
      were significantly higher in GERD patients than the control group (p < 0.001).
      Grade 0 serum nitrates was significantly higher than the control group (p < 0.05)
      with some overlap between the individual values of the two groups. Serum VIP was
      significantly higher in grade 0 group compared to control group (p < 0.001) with
      no overlap in the individual values. There was a significant positive correlation
      between the grade of lower end esophagitis and each of serum nitrate and VIP (p <
      0.001), as well as between serum nitrate and each of serum VIP, cigarette smoking
      index (CSI) and BMI (p < 0.001). CONCLUSION: Abnormally high levels of serum VIP
      and NO may have a role in the pathogenesis of GERD. Exposure of esophageal mucosa
      to noxious effect of acid refluxed due to the relaxant effect of VIP on lower
      esophageal sphincter may cause increased NO levels. BMI and CSI are risk factors
      for GERD progression.

PMID- 12499000
TI  - Myoglobin, creatine kinase MB isoforms and creatine kinase MB mass in early
      diagnosis of myocardial infarction in patients with acute chest pain.
AB  - OBJECTIVES: Measurements of myoglobin and creatine kinase (CK)-MB isoforms have
      been suggested to be sensitive tests for the early diagnosis of myocardial
      infarction (MI). We have investigated the utility of myoglobin, creatine kinase
      (CK)-MB isoforms and creatine kinase MB mass (CK-MBm) in early diagnosis of MI
      using cardiac troponin T (cTnT) positivity as a reference. DESIGN AND METHODS:
      The study population comprised 440 patients who had had chest pain for less than
      12 h. Patients were divided into cTnT negative (cTnT-) or cTnT positive (cTnT+)
      patients (concentration of cTnT >0.1 microg/L at two different time points during
      72 h). RESULTS: At the time of admission to the emergency department receiver
      operating characteristics (ROC) curves of CK-MB isoforms and CK-MBm were not
      better than that of myoglobin. Six hours after admission CK-MB isoforms and CK
      MBm provided statistically significantly larger areas under the curve (AUC) than
      myoglobin (p < 0.01). When ROC curves were related to the onset of chest pain (<
      3 h, 3-6 h, and > 6 h) there were no significant differences between the cardiac
      markers studied. CONCLUSIONS: According to the present findings, CK-MB isoforms
      or myoglobin offer no advantage over CK-MBm as early markers of myocardial
      infarction.

PMID- 12499001
TI  - In-vivo quantification of hepatic 11beta-hydroxysteroid dehydrogenase type I
      activity--a preliminary study.

PMID- 12499003
TI  - Pasture-based dairying: challenges and rewards for New Zealand producers.
AB  - New Zealand dairying farm systems are principally pasture-based or seasonal
      supply. Features of these systems and their management are described, together
      with their advantages and limitations. The characteristics of reproductive
      management needed to attain satisfactory economic performance of these farm
      systems is discussed. The low-cost pasture-based seasonal system dictates that
      animals be bred over a very short period compared to many overseas countries and
      this is assisted in particular by the use of hormonal treatment for anoestrum.
      Oestrus synchrony is not widely used although uptake is increasing, particularly
      in large herds. The constraints imposed by the farming system represent a
      significant challenge to the application of embryo technologies as embryos must
      be recovered and transferred over the short period between calving and artificial
      insemination and farmers demand either a high pregnancy rate or a high value calf
      to compensate for the cost of the procedure and any delay in achieving a
      pregnancy.

PMID- 12499004
TI  - Dairy cattle production in Europe.
AB  - The European Union (EU) is a major player on world markets for most dairy
      products and produces the largest single share of the global market. Dairying is
      one of the most profitable sectors of EU agriculture. Milk yields per cow have
      increased steadily in every member state between 1985 and 1997. Overall EU dairy
      production continues to follow a trend towards increased intensification on a
      smaller number of larger, more specialised production units. In this paper we
      highlight the main characteristics of dairy cattle production in the EU, as well
      as their impact on cow and herd reproductive performances. AI is widely used in
      areas where there is high input:high output farming and farmers' primary
      objective is to have each cow produce a calf every 12 months without any
      particular calving pattern. The use of embryo technologies is increasing and in
      some areas (e.g. IVP embryo transfers) Europe leads the world. In most areas of
      Europe, because of both year round calving and ethical or consumer concerns,
      hormones are mainly used to treat reproductive diseases and not for
      pharmaceutical control of breeding.

PMID- 12499005
TI  - Artificial insemination: the state of the art.
AB  - The history of research into artificial insemination (AI) is over two centuries
      old and its commercial application now spans 75 years. It is appropriate to
      reflect on the contribution of this powerful method of gene dispersal. AI remains
      as one of the most important assisted reproductive technologies. The three
      cornerstones for its application are: it is simple, economical and successful.
      The importance of AI will be challenged in the next few decades. The remarkable
      progress made in other assisted reproductive technologies does have the potential
      to rapidly generate offspring. The challenge for any of these reproductive
      technologies to attain widespread use is to match AI in being simple, economical
      and successful. This review aims at capturing the salient advances in AI, the
      comparisons with natural mating and other reproductive technologies, and, whether
      the future of AI will be challenged. It predicts what the new horizon looks like
      and the role that AI will play in the overall reproductive technologies
      landscape.

PMID- 12499006
TI  - Economics of selecting for sex: the most important genetic trait.
AB  - Over 20,000 calves have resulted from artificial insemination (AI) of cattle with
      sexed, frozen/thawed sperm in the course of experimentation in several countries,
      and from commercial sales in the United Kingdom. This technology likely will
      become commercially available in many countries within a few years. Accuracy of
      the process is about 90% for either sex, and resulting calves appear to be no
      different from non-sexed controls in birthweight, mortality, rate of gain, and
      incidence of abnormalities. The main determinants of the extent of use of sexed
      sperm will be pregnancy rate and cost. Fertility of low doses (1.5 x 10(6)-2 x
      10(6)) of sexed, frozen sperm for AI of heifers usually has been in the range of
      70-80% of unsexed sperm at normal doses (10 x 10(6)-20 x 10(6) sperm) in well
      managed herds; it has been lower in poorly managed herds, and likely will be
      lower with lactating dairy cows. It is expected that fertility of sexed sperm
      will increase significantly due to very recent improvements in the hydrodynamics
      of the sexing process and potential improvements in cryopreservation procedures.
      It is unclear how sexed sperm will be priced; the cost of sexed sperm for cattle
      will likely be more than double the cost of unsexed sperm in most markets. The
      economic benefit of using sexed sperm also will depend on the baseline fertility
      of the herd since at lower fertility, it takes more doses of semen per calf
      produced. It is noted that for a small percentage of elite cattle, the economics
      of using sexed sperm do not depend primarily on increased production or
      efficiency of producing meat or milk, but rather on factors such as scarcity,
      tradition, cattle show winnings, and biosecurity during herd expansion. Until
      sorting efficiencies improve and costs decline, sales likely will be limited
      primarily to these niche markets. With near normal fertility and a premium for
      sexing in the range of US$ 10 per insemination dose, sexed sperm likely would
      become economically and environmentally beneficial for many, if not most
      populations of cattle being bred by AI.

PMID- 12499007
TI  - Bovine embryo technologies.
AB  - Embryo technologies are a combination of assisted reproduction, cellular and
      molecular biology and genomic techniques. Their classical use in animal breeding
      has been to increase the number of superior genotypes but with advancement in
      biotechnology and genomics they have become a tool for transgenesis and
      genotyping. Multiple ovulation and embryo transfer (MOET) has been well
      established for many years and still accounts for the majority of the embryos
      produced worldwide. However, no progress has been made in the last 20 years to
      increase the number of transferable embryos and to reduce the side effects on the
      reproductive performance of the donors. In vitro embryo production (IVP) is a
      newer and more flexible approach, although it is technically more demanding and
      requires specific laboratory expertise and equipment that are most important for
      the quality of the embryos produced. Somatic cell cloning is a rapidly developing
      area and a very valuable technique to copy superior genotypes and to produce or
      copy transgenic animals. More knowledge in oocyte and embryo biology is expected
      to shed new light on the early developmental events, including epigenetic changes
      and their long lasting effect on the newborn.Embryo technologies are here to stay
      and their use will increase as advances in the understanding of the mechanisms
      governing basic biological processes are made.

PMID- 12499008
TI  - Factors affecting commercial application of embryo technologies in New Zealand: a
      modelling approach.
AB  - New reproductive technologies include sexed sperm and embryo-based technologies.
      The technology of sperm sexing, for various reasons, is not available in New
      Zealand and its use has not been modelled. Embryo technologies are however
      already in use on a limited scale and various scenarios for their use in both the
      dairy and beef industries in New Zealand have been modelled. This review briefly
      discusses the various technologies available and some of their potential
      strengths and weaknesses. In the dairy industry, modelling has been used to
      simulate the production of breeding bulls for large breeding companies and the
      production of replacement heifers in dairy herds. For the beef industry, similar
      modelling has been carried out to determine the opportunities for more efficient
      beef production. All the models confirmed that at current levels of performance,
      embryo-based reproductive technologies are usually not profitable in New Zealand
      except in niche market situations where the returns from the resulting offspring
      are significantly greater than can be obtained from natural mating or artificial
      insemination (AI) reproduction systems. This is confirmed by the low uptake of
      these technologies in this country to date. Even if performance lifts to levels
      similar to AI, profitability is likely to occur only if the costs of pregnancies
      to embryo-based reproductive technologies can occur at prices less than two to
      four times greater than AI or natural mating. This break-even requirement depends
      on the returns that can be achieved and the advantages that can be captured by
      the technology over and above those available from AI or natural mating. Two new
      uses for reproductive technologies in dairy cattle could be the proliferation of
      novel or rare genotypes from gene discovery programs and improving the female
      reproductive rate for optimal marker assisted selection. In both these uses the
      technology is not at present competing with AI or natural mating. The challenge
      exists therefore for the biological scientists to satisfy these requirements,
      coupled with the ethical and human factors involved in the introduction of any
      new technology. Potential end users of the technologies have been surveyed. They
      are quite positive about the technologies provided they can use them profitably
      and are keen to obtain more information about them.

PMID- 12499009
TI  - Factors affecting commercial application of embryo technologies in dairy cattle
      in Europe--a modelling approach.
AB  - Reproductive techniques have a major impact on the structure of breeding
      programmes, the rate of genetic gain and dissemination of genetic gain in
      populations. This manuscript reviews the impact of reproductive technologies on
      the underlying components of genetic gain and inbreeding with special reference
      to the role of female reproductive technology. Evaluation of alternative breeding
      schemes should be based on genetic gain while constraining inbreeding. Optimum
      breeding schemes can be characterised by: decreased importance of sib
      information; increased accuracy at the expense of intensity; and a factorial
      mating strategy. If large-scale embryo cloning becomes feasible, this will have a
      small impact on the rate of genetic gain but will have a large impact on the
      structure of breeding programmes.

PMID- 12499010
TI  - Factors affecting oocyte quality and quantity in commercial application of embryo
      technologies in the cattle breeding industry.
AB  - With the introduction of multiple ovulation, embryo recovery and transfer
      techniques (MOET) plus embryo freeze-thaw methods in the early 1980s, the
      breeding industry has the tools in hand to increase the number of calves from
      donors of high genetic merit. In the early 1990s, the introduction of ovum pick
      up followed by in vitro embryo production (OPU-IVP) opened up even greater
      possibilities. Using these technologies, we challenge biological mechanisms in
      reproduction. Where normally one oocyte per estrous cycle will develop to
      ovulation, now numerous other oocytes that otherwise would have degenerated are
      expected to develop into an embryo. Completion of oocyte growth and pre
      maturation in vivo before final maturation both appear to be essential phases in
      order to obtain competence to develop into an embryo and finally a healthy
      offspring. In order to increase oocyte quality and quantity in embryo production
      technologies, current procedures focus primarily on improving the homogeneity of
      the population of oocytes with regard to growth and state of pre-maturation at
      the start of a treatment. In the case of MOET, dominant follicle removal (DFR)
      before superovulation treatment improves the number of viable embryos per session
      from 3.9 to 5.4 in cows but not in heifers and a prolonged period of follicle
      development obtained by preventing release of the endogenous LH surge increases
      the number of ova but not the number of viable embryos per session. In the case
      of OPU-IVP, the frequency of OPU clearly affects quantity and quality of the
      collected oocytes and FSH stimulation prior to OPU every 2 weeks resulted in 3.3
      embryos per session. Analysis of 7,800 OPU sessions demonstrated that the oocyte
      yield is dependent on the team, in particular, the technician manipulating the
      ovaries. It is concluded that an increased understanding of the processes of
      oocyte growth, pre- and final maturation will help to improve the efficiency of
      embryo technologies. However, somewhere we will meet the limits dictated by
      nature.

PMID- 12499011
TI  - In vitro production of bovine embryos and their application for embryo transfer.
AB  - This review introduces newly developed serum-free media (IVD101 and IVMD101),
      that are effective for producing high yields of transferable embryos of good
      quality from in vitro-matured and -fertilized oocytes. Both serum-free media
      produced better results than serum-containing medium, including increased rates
      of blastocyst formation, post-thaw embryo viability, and pregnancy after
      transfer. In addition, reduced risks of calf mortality and large calf syndrome
      were also observed for the serum-free-derived embryos. Serum-derived embryos
      contained a large number of lipid droplets and immature mitochondria in their
      cytoplasm that may account for the lower production of transferable embryos and
      poor embryo quality. A non-invasive technique using scanning electrochemical
      microscopy was successful in quantitatively measuring oxygen consumption of
      single embryos. This technique may prove to be reliable for predicting embryo
      viability and subsequent developmental ability.

PMID- 12499012
TI  - Improving successful pregnancies after embryo transfer.
AB  - Over the past 20 years the rate of blastocyst development in vitro has improved
      through the development of sequential defined media, refining the oxygen
      concentrations during culture and providing substrates to ameliorate free radical
      accumulation. Despite these advances there has been little progress in improving
      calving rates after the transfer of in vitro produced embryos. This suggests that
      the culture conditions have been very effective in enabling those fertilised
      oocytes to reach the blastocyst stage that otherwise would not occur in vivo. We
      suggest that the next advance by which the embryo transfer technology gains more
      acceptance in cattle production will be identifying those cows which are
      intrinsically superior recipients. This must be coupled to the development of non
      invasive assessments of the developmental competence of both the oocyte and the
      blastocyst. Until these two goals are achieved the ET industry will remain static
      and unable to overcome the economic loss caused by embryo mortality occurring 7
      10 days after transfer.

PMID- 12499013
TI  - Implementation challenges of smart semen adn embryo technologies in cattle.
      Proceeding to the IETS Post-Conference Satellite Symposium. Auckland, New
      Zealand. January 15, 2003.

PMID- 12499014
TI  - Gene expression and chromatin structure in the pre-implantation embryo.
AB  - The pre-implantation period of mammalian development includes the formation of
      the zygote, the activation of the embryonic genome (EGA), and the beginning of
      cellular differentiation. During this period, protamines are replaced by
      histones, the methylated haploid parental genomes undergo demethylation following
      formation of the diploid zygote, and maternal control of development is succeeded
      by zygotic control. Superimposed on this activation of the embryonic genome is
      the formation of a chromatin-mediated transcriptionally repressive state
      requiring enhancers for efficient gene expression. The development of this
      transcriptionally repressive state most likely occurs at the level of chromatin
      structure, because inducing histone hyperacetylation relieves the requirements
      for enhancers. Characterization of zygotic mRNA expression patterns during the
      pre-implantation period and their relationship to successful development in vitro
      and in vivo will be essential for defining optimized culture conditions and
      nuclear transfer protocols. The focus of this review is to summarize recent
      advances in this field and to discuss their implications for developmental
      biology.

PMID- 12499015
TI  - Mammalian epigenomics: reprogramming the genome for development and therapy.
AB  - Epigenetic modifications of DNA and chromatin are important for genome function
      during development and in adults. DNA and chromatin modifications have central
      importance for genomic imprinting and other aspects of epigenetic control of gene
      expression. In somatic lineages, modifications are generally stably maintained
      and are characteristic of different specialized tissues. The mammalian genome
      undergoes major reprogramming of modification patterns in germ cells and in the
      early embryo. Some of the factors that are involved both in maintenance and in
      reprogramming, such as methyltransferases, are being identified. Epigenetic
      reprogramming is deficient in animal cloning, which is a major explanation for
      the inefficiency of the cloning procedure. Deficiencies in reprogramming are
      likely to underlie the occurrence of epimutations and of epigenetic inheritance.
      Environmental factors can alter epigenetic modifications and may thus have long
      lasting effects on phenotype. Epigenomics methods are being developed to
      catalogue genome modifications under normal and pathological conditions.
      Epigenetic engineering is likely to play an important role in medicine in the
      future.

PMID- 12499016
TI  - Nuclear reprogramming of cloned embryos produced in vitro.
AB  - Despite the fact that cloned animals derived from somatic cells have been
      successfully generated in a variety of mammalian species, there are still many
      unsolved problems with current cloning technology. Somatic cell nuclear transfer
      has shown several developmental aberrancies, including a high rate of abortion
      during early gestation and increased perinatal death. One cause of these
      developmental failures of cloned embryos may reside in the epigenetic
      reprogramming of somatic donor genome. In mammals, DNA methylation is an
      essential process in the regulation of transcription during embryonic development
      and is generally associated with gene silencing. A genome-wide demethylation may
      be a prerequisite for the formation of pluripotent stem cells that are important
      for later development. We analyzed methylation patterns in cloned bovine embryos
      to monitor the epigenetic reprogramming process of donor genomic DNA. Aberrant
      methylation profiles of cloned bovine embryos were observed in various genomic
      regions, except in single-copy gene sequences. The overall genomic methylation
      status of cloned embryos was quite different from that of normal embryos produced
      in vitro or in vivo. These results suggest that the developmental failures of
      cloned embryos may be due to incomplete epigenetic reprogramming of donor genomic
      DNA. We expect that advances in understanding the molecular events for
      reprogramming of donor genome will contribute to clarify the developmental
      defects of cloned embryos.

PMID- 12499017
TI  - Coordination between donor cell type and cell cycle stage improves nuclear
      cloning efficiency in cattle.
AB  - Several studies have shown that both quiescent and proliferating somatic donor
      cells can be fully reprogrammed after nuclear transfer (NT) and result in viable
      offspring. So far, however, no comparative study has conclusively demonstrated
      the relative importance of donor cell cycle stage on nuclear cloning efficiency.
      Here, we compare two different types of bovine fetal fibroblasts (BFFs) that were
      synchronized in G(0), G(1), and different phases within G(1). We show that for
      non-transgenic (non-TG) fibroblasts, serum starvation into G(0) results in a
      significantly higher percentage of viable calves at term than synchronization in
      early G(1) or late G(1). For transgenic fibroblasts, however, cells selected in
      G(1) show significantly higher development to calves at term and higher post
      natal survival to weaning than cells in G(0). This suggests that it may be
      necessary to coordinate donor cell type and cell cycle stage to maximize overall
      cloning efficiency.

PMID- 12499018
TI  - Bringing up small oocytes to eggs in pigs and cows.
AB  - It has been known that the mammalian ovary contains a huge number of non-growing
      small oocytes, of which only a small number grow to their final size, mature, and
      are ovulated. Artificial maturation of small oocytes could provide a new source
      of mature eggs for livestock production and assisted reproduction in humans and
      in endangered species. Two methods have been used for oocyte growth, in vitro
      growth (IVG) culture and xenotransplantation. By these methods, oocytes in some
      species grow up to their final size and acquire developmental competence,
      although the methods are still at the experimental stage. The experiments remind
      us of many basic questions in mammalian oogenesis: Does the oocyte require
      certain stimuli to initiate growth? How are the few oocytes selected to grow to
      final size? How do they grow up in follicular units? How do they acquire meiotic
      competence during the growth phase? This paper will give some clues to answer
      these questions by presenting our recent data from IVG and xenotransplantation
      experiments, and by illustrating differences between the oocytes of mice and
      larger animals.

PMID- 12499019
TI  - Prospects for spermatogenesis in vitro.
AB  - In recent years, extraordinary progress has been made in a broad range of
      reproductive technologies, including spermatogonial transplantation in the male.
      However, effective procedures for the complete recapitulation of spermatogenesis
      in vitro, including meiosis, have remained elusive. Such procedures have the
      potential to facilitate (1) mechanistic studies of spermatogenesis, (2) directed
      genetic modification of the male germ line, and (3) treatment of male factor
      infertility. Early studies demonstrated the importance of germ cell-Sertoli
      association for germ cell survival in vitro. Recently, evidence for male germ
      cell survival and progression through meiosis has been reported for the rat,
      mouse, and man. We demonstrated the expression of spermatid-specific genes
      (protamine and transition protein 1) by alginate-encapsulate neonatal bull testis
      cells after 10 weeks in culture, suggesting that meiosis had occurred. Although
      identifiable germ cells in these cultures were very sparse, some indication of
      acrosome development was observed. Following round spermatid injection (ROSI)
      with presumptive spermatids produced in vitro, 50% of blastocysts produced were
      diploid and 37% were Y-chromosome positive. Improved culture conditions, which
      promote germ cell survival, differentiation, and proliferation, are essential for
      in vitro spermatogenesis (IVS) to become a useful technology. Other approaches to
      male germ cell manipulation and spermatid production are discussed.

PMID- 12499020
TI  - New microinsemination techniques for laboratory animals.
AB  - Since the development of a reliable mouse intracytoplasmic sperm injection (ICSI)
      technique in 1995, microinsemination techniques have been widely applied in
      several laboratory species. As gametes and embryos have specific biological and
      biochemical features according to the species, technical improvements are
      necessary for successful microinsemination that subsequently leads to normal
      fetal development in several species. Recent advanced reproductive research
      involving genetic engineering often depends on microinsemination techniques that
      require a high degree of skill, and new human assisted reproductive technology
      (ART) requires experimental models using laboratory animals. The accumulation of
      technical improvements in these fields should accelerate the development of
      microinsemination techniques in mammals, including humans.

PMID- 12499021
TI  - Development of efficient strategies for the production of genetically modified
      pigs.
AB  - Although pronuclear DNA micro-injection has long been the most reliable method to
      produce transgenic pigs, the efficiency of production of transgenic offspring is
      generally plagued by 1% of the DNA-injected embryos. Therefore, a problem with
      this method is the need for large numbers of pronuclear stage embryos. One great
      advancement would be the use of in vitro-matured (IVM) oocytes for the purpose of
      transgenic pig production. High developmental competence of IVM oocytes was
      proven by transfer of parthenogenetic IVM oocytes. A combined method of sperm
      vectors with the IVM of oocytes would make the production of transgenic pigs
      remarkably feasible. Rate of blastocyst formation following intracytoplasmic
      sperm injection (ICSI) by frozen sperm was over 20%, and transgene was expressed
      in approximately 50% of blastocysts generated. Somatic cell nuclear transfer
      would enable more efficient and sophisticated genetic modification of the pig.
      Simultaneous comparison between two nuclear transfer methods by electro-fusion
      and intracytoplasmic injection revealed clear differences in the pattern of
      nuclear remodeling and development of the reconstructed embryos. To specify the
      donor cell type that allows efficient genetic modification and easy reprogramming
      or to establish such cell lines is a critical issue in pig cloning. We tested pre
      adipocytes from the subcutaneous adipose tissue of adult pigs for nuclear
      transfer. Cell cycle synchronization by differentiation induction is unique to
      the pre-adipocytes. Frequency of apoptosis was low in the cells synchronized by
      differentiation induction compared with other synchronization methods, including
      serum starvation, confluency, and chemical treatment. It would be of great worth
      if cryopreserved clone embryos were available. We have demonstrated that
      cryopreservation of in vitro-produced porcine embryos as well as clone
      blastocysts is possible by our unique method.

PMID- 12499022
TI  - Artificial chromosome vectors and expression of complex proteins in transgenic
      animals.
AB  - Artificial chromosome vectors are autonomous, replicating DNA sequences
      containing a centromere, two telomeres and origins of replication. Artificial
      chromosomes have been proposed as possible vectors for transferring very large
      sequences of DNA into animals. Our goal has been to insert the entire human heavy
      and light-chain immunoglobulin loci into cattle as a step in developing a
      production system for large quantities of human therapeutic polyclonal
      antibodies. A mitotically stable fragment of chromosome 14, containing the human
      heavy-chain locus, was identified. A chromosome cloning system was used to
      transfer the human lambda locus from an unstable chromosome 22 fragment to the
      chromosome 14 fragment to create a human artificial chromosome (HAC) carrying
      both immunoglobulin loci. The HAC vector was introduced into bovine primary
      fibroblasts. Selected fibroblast clones were rejuvenated and expanded by
      producing cloned fetuses. Cloned fetal cells were selected and recloned to
      produce 21 healthy, transchromosomic (Tc) calves. Four were analyzed and shown to
      functionally rearrange both heavy- and light-chain human immunoglobulin loci and
      produce human polyclonal antibodies. These results demonstrate the feasibility of
      using HAC vectors for production of transgenic livestock. More importantly, Tc
      cattle containing human immunoglobulin genes may be used to produce novel human
      polyclonal therapeutics.

PMID- 12499023
TI  - Transgenic swine for biomedicine and agriculture.
AB  - Initial technologies for creating transgenic swine only permitted random
      integration of the construct. However, by combining the technology for homologous
      recombination in fetal somatic cells with that of nuclear transfer (NT), it is
      now possible to create specific modifications to the swine genome. The first such
      example is that of knocking out a gene that is responsible for hyperacute
      rejection (HAR) when organs from swine are transferred to primates. Because swine
      are widely used as models of human diseases, there are opportunities for genetic
      modification to alter these models or to create additional models of human
      disease. Unfortunately, some of the offspring resulting from NT have abnormal
      phenotypes. However, it appears that these abnormal phenotypes are a result of
      epigenetic modifications and, thus, are not transmitted to the offspring of the
      clones. Although the technique of producing animals with specific genetic
      modifications by NT has been achieved, improvements to the NT technique as well
      as improvements in the culture conditions for somatic cells and the techniques
      for genetic modification are still needed.

PMID- 12499024
TI  - Commercialization of animal biotechnology.
AB  - Commercialization of animal biotechnology is a wide-ranging topic for discussion.
      In this paper, we will attempt to review embryo transfer (ET) and related
      technologies that relate to food-producing mammals. A brief review of the history
      of advances in biotechnology will provide a glimpse to present and future
      applications. Commercialization of animal biotechnology is presently taking two
      pathways. The first application involves the use of animals for biomedical
      purposes. Very few companies have developed all of the core competencies and
      intellectual properties to complete the bridge from lab bench to product. The
      second pathway of application is for the production of animals used for food.
      Artificial insemination (AI), embryo transfer, in vitro fertilization (IVF),
      cloning, transgenics, and genomics all are components of the toolbox for present
      and future applications. Individually, these are powerful tools capable of
      providing significant improvements in productivity. Combinations of these
      technologies coupled with information systems and data analysis, will provide
      even more significant change in the next decade. Any strategies for the
      commercial application of animal biotechnology must include a careful review of
      regulatory and social concerns. Careful review of industry infrastructure is also
      important. Our colleagues in plant biotechnology have helped highlight some of
      these pitfalls and provide us with a retrospective review. In summary, today we
      have core competencies that provide a wealth of opportunities for the members of
      this society, commercial companies, producers, and the general population.
      Successful commercialization will benefit all of the above stakeholders.

PMID- 12499025
TI  - New commercial opportunities for advanced reproductive technologies in horses,
      wildlife, and companion animals.
AB  - As advanced reproductive technologies become more efficient and repeatable in
      livestock and laboratory species, new opportunities will evolve to apply these
      techniques to alternative and non-traditional species. This will result in new
      markets requiring unique business models that address issues of animal welfare
      and consumer acceptance on a much different level than the livestock sector.
      Advanced reproductive technologies and genetic engineering will be applied to
      each species in innovative ways to provide breeders more alternatives for the
      preservation and propagation of elite animals in each sector. The
      commercialization of advanced reproductive techniques in these niche markets
      should be considered a useful tool for conservation of genetic material from
      endangered or unique animals as well as production of biomedical models of human
      disease.

PMID- 12499026
TI  - Embryo technologies in the horse.
AB  - Recent studies demonstrated that zwitterionic buffers could be used for
      satisfactory storage of equine embryos at 5 degrees C. The success of freezing
      embryos is dependent upon size and stage of development. Morulae and blastocysts
      <300 microm can be slowly cooled or vitrified with acceptable pregnancy rates
      after transfer. The majority of equine embryos are collected from single
      ovulating mares, as there is no commercially available product for superovulation
      in equine. However, pituitary extract, rich in FSH, can be used to increase
      embryo recovery three- to four-fold. Similar to human medicine, assisted
      reproductive techniques have been developed for the older, subfertile mare.
      Transfer of in vivo-matured oocytes from young, healthy mares into a recipient's
      oviduct results in a 70-80% pregnancy rate compared with a 30-40% pregnancy rate
      when the oocytes are from older, subfertile mares. This procedure can also be
      used to evaluate in vitro maturation systems. In vitro production of embryos is
      still quite difficult in the horse. However, intracytoplasmic sperm injection
      (ICSI) has been used to produce several foals. Cleavage rates of 60% and
      blastocyst rates of 30% have been reported after ICSI of in vitro-matured
      oocytes. Gamete intrafallopian tube transfer (GIFT) is a possible treatment for
      subfertile stallions. Transfer of in vivo-matured oocytes with 200,000 sperm into
      the oviduct of normal mares resulted in a pregnancy rate of 55-82%. Oocyte
      freezing is a technique that has proven difficult in most species. However,
      equine oocytes vitrified in a solution of ethylene glycol, DMSO, and Ficoll and
      loaded onto a cryoloop resulted in three pregnancies of 26 transfers and two live
      foals produced. Production of a cloned horse appears to be likely, as several
      cloned pregnancies have recently been produced.

PMID- 12499027
TI  - Current status of embryo technologies in sheep and goat.
AB  - This review presents an overview of the technical bases of in vivo and in vitro
      embryo production in sheep and goat. The current limitations of in vivo
      production, such as variability of response to the hormonal treatment,
      fertilization failure in females showing a high ovulatory response, and the
      importance of premature regressed CL in the goat, are described along with
      possibilities for improvement. The new prospects offered by in vitro embryo
      production, by repeated ovum pick-up from live females and by juvenile breeding,
      are presented along with their limiting steps and research priorities. The recent
      improvements of embryo production and freezing technologies could be used for
      constitution of flocks without risks of disease transmission and will allow wider
      propagation of valuable genes in small ruminants populations in the future.

PMID- 12499028
TI  - New developments reproductive technologies in deer.
AB  - In vitro embryo production is the platform for advanced reproductive
      technologies, such as cloning. The in vitro embryo production system developed
      for farmed red deer (Cervus elaphus) evolved along similar lines to that
      pioneered by other domestic species researchers. However, applying existing in
      vitro embryo production methods from these other species resulted in limited
      success and has necessitated developing a species-specific methodology for red
      deer based on the their physiology. Analysis of oviduct fluid led to the
      development of a semi-defined fertilization and culture media system, Deer
      Synthetic Oviduct Fluid (DSOF), which resulted in successful culture of red deer
      embryos to the blastocyst stage. Transvaginal ultrasound-guided ovarian
      examination and ovum pickup has enabled the study of seasonality constraint and
      propagation from selected female genetics, respectively. During the 4-month
      breeding season (April-July), 15% of cleaved oocytes developed to blastocysts,
      whereas no blastocysts developed from oocytes collected after July. The process
      of developing an in vitro embryo production system for farmed red deer may serve
      as a beneficial model for the propagation of endangered cervine species.

PMID- 12499029
TI  - Insertion of the Multiload Cu375 intrauterine device; experience in over 16,000
      New Zealand women.
AB  - Insertion of Multiload Cu375 was studied in 16,159 women in a 10-year prospective
      observational cohort study in New Zealand. Of 17,468 insertions, about 9% were
      performed in nulliparous women. Problems fitting Multiload Cu375 (e.g., failed or
      difficult insertion) were experienced during approximately 2% of all insertions.
      The incidence of these was significantly higher in nulliparous women compared to
      parous women. Adverse reactions to insertion (e.g., pain, bleeding) occurred in
      1.2% of all insertions, with nulliparous women experiencing significantly more
      adverse reactions than parous women. The insertions were performed by 1,700
      different doctors in New Zealand with general practitioners performing 92% of
      these. Doctors who reported inserting over 100 devices in the study period
      experienced significantly less insertion problems than doctors who reported
      inserting less than 10 devices. This study suggests that insertion of Multiload
      Cu375 in a mixed community setting is associated with few inserting problems and
      adverse reactions to insertion. Risk factors identified for inserting problems
      included nulliparity and experience of the doctor inserting the intrauterine
      device.

PMID- 12499030
TI  - Primary dysmenorrhea treatment with a desogestrel-containing low-dose oral
      contraceptive.
AB  - This randomized, double-blind, placebo-controlled exploratory study examined the
      efficacy and safety of a low-dose oral contraceptive (Mircette),
      desogestrel/ethinyl estradiol [DSG/EE] and ethinyl estradiol [EE]) in relieving
      the symptoms of dysmenorrhea. Twenty-three clinics in the United States enrolled
      77 women (age < or =32 years) with primary dysmenorrhea documented for at least
      four consecutive cycles. Forty participants received DSG/EE&EE and 37 received
      placebo for four consecutive 28-day cycles. The intensity of menstrual-related
      distress was measured with the Menstrual Distress Questionnaire (MDQ). Patient
      diaries were used to assess number of school/work days missed as well as the use
      of rescue medication. Participants receiving DSG/EE&EE recorded reduced menstrual
      pain severity, lower total MDQ scores, and significantly less menstrual cramping.
      No significant change in bloating, anxiety, loneliness, weight gain, or acne was
      reported. The DSG/EE&EE formulation shows promise for the treatment of primary
      dysmenorrhea and was well tolerated by the participants in this study.

PMID- 12499031
TI  - Clinical comparative study of oral contraceptives containing 30 microg
      ethinylestradiol/150 microg levonorgestrel, and 35 microg ethinylestradiol/250
      microg norgestimate in Thai women.
AB  - The study was conducted to compare cycle control, efficacy and side effects of
      two oral contraceptives containing 30 microg ethinylestradiol (EE)/150 microg
      levonorgestrel (LNG) and 35 microg ethinylestradiol (EE)/250 microg norgestimate
      (NGM). An open-label, randomized, comparative study was conducted in which 140
      healthy women received the 30 microg EE/150 microg LNG or 35 microg EE/250 microg
      NGM preparation for six treatment cycles. There were no significant statistical
      differences between both groups in terms of cycle length and amount of withdrawal
      bleeding. The mean duration in the 35 microg EE/250 microg NGM group was longer
      than 30 microg EE/150 microg LNG group with significant statistical difference.
      More patients in 35 microg EE/250 microg NGM group experienced BTT at each cycle
      compared with the 30 microg EE/150 microg LNG group, but was not statistically
      significant. There was no amenorrhea nor pregnancies occurring in either group.
      No significant changes in body weight or blood pressure were found in both
      groups. The incidence of adverse events in both groups was low and tended to
      decrease with time. Statistically significant differences were observed for
      headache and dizziness, which occurred more in the 30 microg EE/150 microg LNG
      group. In conclusion, 35 microg EE/250 microg NGM provides reliable contraceptive
      efficacy. It also provides good cycle control equal to 30 microg EE/150 microg
      LNG with a lower incidence of minor adverse effects such as headache and
      dizziness compared to 30 microg EE/150 microg LNG.

PMID- 12499032
TI  - A comparison of cycle control, efficacy, and side effects among healthy Thai
      women between two low-dose oral contraceptives containing 20 microg
      ethinylestradio1/75 microg gestodene (Meliane) and 30 microg ethinylestradio1/75
      microg gestodene (Gynera).
AB  - The purpose of this study was to compare cycle control, efficacy and side effects
      of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg
      gestodene, with a reference preparation containing 30 microg ethinylestradiol
      combined with 75 microg gestodene. From the study, it was demonstrated that the
      two regimens had no difference in cycle control, efficacy, and side effects. The
      occurrence of spotting and breakthrough bleeding was low and was not different
      between these two preparations. The most common adverse events in both treatment
      groups were nausea, vomiting, dizziness, and chloasma. There were no
      statistically significant change in body weight and blood pressure in both groups
      at the end of study. It is concluded that both preparations are good cycle
      control, reliable and low side effects oral contraceptives.

PMID- 12499033
TI  - Randomized controlled study of the influence of two low estrogen dose oral
      contraceptives containing gestodene or desogestrel on carbohydrate metabolism.
AB  - This study compared the impact on carbohydrate metabolism of two combinedoral
      contraceptives (COCs). This open-label, single-center trial enrolled participants
      for a total of 15 cycles. Thirty-six women were randomized to receive either 20
      microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) or 20 microg ethinyl
      estradiol and 150 microg desogestrel (DSG) daily for 21 days out of 28. A glucose
      tolerance test was performed at baseline and cycles 6 and 13. The area under the
      curve (AUC) for glucose increased in both study groups. The change was
      statistically significant (p = 0.036) for the 20 EE/75 GSD group at cycle 6
      versus baseline. Fasting blood glucose at cycle 13 was significantly (p < 0.01)
      higher for both treatment groups compared to baseline. No changes were found for
      fasting insulin and fasting C-peptide levels or for the AUCs of insulin or C
      peptide. Both regimens were well tolerated. Gestodene and desogestrel in
      combination with 20-microg ethinyl estradiol induce similar changes in
      carbohydrate metabolism which are smaller than those described earlier for COCs
      containing higher estrogen doses or more androgenic progestins such as
      levonorgestrel.

PMID- 12499034
TI  - Knowledge and attitudes about the differences between emergency contraception and
      medical abortion among middle-class women and men of reproductive age in Mexico
      City.
AB  - Two reproductive technologies--emergency contraception and medical abortion--have
      the potential to reduce unintended pregnancy significantly in Latin America. Lack
      of knowledge and negative attitudes about the methods may limit their impact,
      however. Results from focus group discussions with middle-class men and women of
      reproductive age residing in Mexico City indicate that knowledge about emergency
      contraception and medical abortion is low. After being informed about both
      methods, participants supported emergency contraception but tied their support
      for medical abortion to its legal status. Participants remained concerned about
      the methods' efficacy, mechanism of action, and potential to encourage sexual
      risk-taking. While almost all desired greater dissemination of information about
      and access to both methods in Mexico, participants cited religious and cultural
      concerns, as well as barriers in communication with providers and within
      families, as significant challenges. Participants hoped, however, that both
      emergency contraception and medical abortion might play important roles in
      preventing unwanted pregnancy and abortion-related morbidity and mortality in
      Mexico in the future.

PMID- 12499035
TI  - Emergency contraception: knowledge and use among Danish women requesting
      termination of pregnancy.
AB  - The aim of this study was to describe knowledge about and use of emergency
      contraception (EC) among Danish women requesting termination of pregnancy. The
      study included 1514 women (response rate 83.7%) referred during the period August
      2000 to May 2001. Sufficient knowledge of EC was defined as knowledge about both
      the correct time limit and where to acquire the EC. We found adequate knowledge
      in 44.7%. These women were typically younger, better educated and more often
      singles, nulliparae, and users of contraception. No relation was found to the
      type of contraception used or to previous terminations of pregnancies. EC was
      used in the actual pregnancy by 6.6% and 24.1% had used it previously. Actual or
      formers users were characterized in the same way. The general knowledge about EC
      has not improved significantly during the last few years and there is still need
      for information about the correct use of EC.

PMID- 12499036
TI  - Scanning electron microscopic (SEM) changes of the endometrium in women taking
      high doses of levonorgestrel as emergency postcoital contraception.
AB  - Endometrial surface changes by scanning electron microscope were studied in three
      women who intentionally took high doses of levonorgestrel as an emergency
      postcoital contraceptive. Based upon findings of a close link between endometrial
      receptivity and surface integrity, significant alterations of the uterine lining
      structure may represent a drug effect accomplishing endometrial contraception.
      High doses of levonorgestrel (4-6 times more than recommended) caused detectable
      changes on the surface regardless of the menstrual cycle phase when the
      medication was taken. Cycle classification was based on estradiol and
      progesterone hormone levels, which corresponded to the menstrual diary.
      Comparison to control specimens displayed marked restructuralization of the
      endometrium. As a main feature, the number of ciliated cells were reduced, and
      cilia disappeared in the proliferative and periovulatory phase. In the secretory
      phase, pinopodia disappeared and the endometrial integrity broke down. The
      contraceptive effect of levonorgestrel seems to be accomplished by alteration of
      the endometrial surface and, therefore, receptivity.

PMID- 12499037
TI  - Condoms are not a risk factor for sensitization to latex.
AB  - The study was conducted to assess the prevalence of sensitization to latex in a
      group of women with a high risk for atopy and to determine whether the use of
      condoms is a relevant risk factor. In a prospective study, 100 atopic women
      (defined as having specific IgE to common aero- or nutritional allergens) were
      screened for specific IgE antibodies to latex after delivery: Ten of the 100
      women (10%) showed specific IgE to latex. Total IgE concentrations were higher
      with a history of occupational exposure or of symptoms after contact with latex
      (p < 0.05, and p < 0.005, respectively), but condom users were not significantly
      more frequent in the latex-positive group. Our results indicate that prior use of
      condoms does not appear to be a specific risk factor for sensitization to latex
      in post-partum women at high-risk for atopy. Latex-free condoms should only be
      recommended to women already known to be sensitized to latex.

PMID- 12499038
TI  - Magnetic resonance imaging to determine the distribution of a vaginal gel:
      before, during, and after both simulated and real intercourse.
AB  - To provide effective contraception and protection against sexually transmitted
      disease, vaginal gels should maximally cover the cervical os and the vaginal
      epithelium before, during and after intercourse. To non-invasively monitor the
      intravaginal distribution of an applied intravaginal gel, we performed high
      resolution magnetic resonance imaging (MRI) of the female pelvis before, during
      and after both real and simulated sexual intercourse. We sought to determine
      whether simulated intercourse with a plastic phallus could be used as a surrogate
      for real intercourse for such experiments. Dilute gadolinium chelate solution was
      mixed with Gynol-II gel and introduced intravaginally to volunteer female human
      subjects using a conventional applicator. MRI was performed at 1.5 Tesla with a
      surface coil. Imaging of the female pelvis was performed: (1) immediately after
      insertion of the gel; (2) during real intercourse with a male partner (2
      subjects) or simulated intercourse with a plastic phallus (4 subjects); and (3)
      after completion of real or simulated intercourse. Subjects were studied after
      application of both 3 mL and 5 mL of vaginal gel. Measurements of gel thickness
      covering the vaginal mucosa were made digitally using electronic calipers. The
      bolus of gel is initially located in the upper vaginal canal, superior to the
      urogenital diaphragm. Both real and simulated intercourse dramatically increases
      the spread of gel to the lower vagina. The cervix appears to be adequately
      covered with gel both before and after intercourse. Increasing the volume of the
      gel increases initial vaginal mucosal coverage but also increases leakage from
      the introitus. No statistically significant differences in vaginal mucosal
      coverage were found between patients having undergone real vs. simulated
      intercourse, or on post-intercourse scans of 3 mL versus 5 mL. MRI is a
      sensitive, reproducible means of tracking the spread of intravaginal medications.

PMID- 12499039
TI  - The effects of levonorgestrel on various sperm functions.
AB  - Two doses of 750-microg levonorgestrel at 12 h apart is one of the regimens for
      emergency contraception. The mechanism of action of this regimen is not fully
      known. We investigated whether levonorgestrel influences sperm functions and
      thereby, exerts contraceptive activity. The motility, acrosome reaction, zona
      binding capacity, and oocyte fusion capacity of human spermatozoa treated with 1,
      10, and 100 ng/mL levonorgestrel for 3 h were evaluated. Levonorgestrel decreased
      the curvilinear velocity of the treated spermatozoa in a dose-dependent manner. A
      significant decrease in straight-line velocity, average path velocity and
      linearity were also found with 100 ng/mL levonorgestrel treatment. This
      concentration of levonorgestrel, but not others, also marginally decreased (p =
      0.045) the zona binding capacity of the treated spermatozoa. The steroid had no
      effect on acrosome reaction but had a dose-dependent inhibition on spermatozoa
      oocyte fusion. These data show that levonorgestrel affects sperm function only at
      high concentration and the contribution of these effects to emergency
      contraception is unlikely to be significant.

PMID- 12499040
TI  - Use of cauda epididymis extract as immunocontraceptive.
AB  - The objective of this study was to evaluate use of a cauda epididymis extract
      (CEE) as an immunocontraceptive in rats. Twenty-two rats in puberty or 19 rats
      that gave birth once (primipara) were immunized with intraperitoneal (IP)
      injection of CEE. Rats in puberty received one or two injections of CEE
      containing 1.5 x 10(9) sperm/mL, while primipara rats received injections of CEE
      containing 3 x 10(6) sperm/mL up to three times. Animals were tested for the
      presence and concentration of anti-CEE antibody by enzyme-linked immunosorbent
      assay (ELISA) and monitored for pregnancy following natural insemination. Results
      revealed that 38 (92.6%) of the 41 rats were positive for anti-CEE antibodies,
      regardless of animal type or immunization procedure. However, there was no
      relation between pregnancy rates and concentration of anti-CEE antibody in rats
      immunized with CEE. These results indicate that immune response against CEE may
      not play a major role in contraception in rats.

PMID- 12499041
TI  - Effect of styrene maleic anhydride (SMA) on viability and integrity of isolated
      rat oocytes in vitro.
AB  - In vitro spermicidal property of the polymer, styrene maleic anhydride (SMA), a
      compound under clinical trial as an intravasal male contraceptive, is already
      established. The present study was designed to evaluate the effect of the polymer
      (SMA) on the viability and integrity of rat oocytes in vitro. The pH-lowering
      effect of this polymer was evident following precipitation in Medium 199. Oocytes
      became nonviable with clearly resolved granulated cytoplasm following incubation
      with undiluted polymeric first wash medium. Dilution of polymeric wash medium
      prolonged the integrity and viability of oocytes under incubation. The potency of
      the first wash medium in terms of affecting the viability of oocytes was highest
      among different washes and dilutions. Bulging of cytoplasm and an enlarged zona
      pellucida envelope were observed in a few oocytes treated with the first wash.
      These findings have shown that, like sperm, oocytes also lose their integrity and
      viability when coincubated with the polymer or medium containing the polymer.
      However, developing an appropriate technology for delivery is crucial to exploit
      this potency of the polymer for development of a female contraceptive.

PMID- 12499042
TI  - Rat testicular structure and ultrastructure after paracetamol treatment.
AB  - The morphological modifications of Wistar rat testicles were investigated for
      animals treated with paracetamol. The rats (n = 6) received a single dose of 4.4
      mmol/kg paracetamol, while controls (n = 6) received the same volume of
      physiological solution. After 5, 10 and 50 days, the rats were perfused with
      Karnovsky's fixative and processed by routine methods for light and electron
      microscopy. Some altered seminiferous tubules were found, as well as a few
      degenerating tubules. Within the tubules, Sertoli cells appeared fragmented while
      the spermatids showed unusually well-developed rough endoplasmic reticulum and
      Golgi complexes and had irregularly compacted chromatin. Morphologically altered
      late spermatids were found retaining a larger volume of residual cytoplasm than
      spermatids of controls. An indirect cause of alterations was also suggested based
      on the occurrence of dilated blood vessels and edema.

PMID- 12499043
TI  - High frequency repetitive transcranial magnetic over the medial cerebellum
      induces a shift in the prefrontal electroencephalography gamma spectrum: a pilot
      study in humans.
AB  - In the present study the anatomical projections from the medial cerebellum to the
      prefrontal cortex (PFC) were investigated in healthy human subjects, using high
      frequency repetitive transcranial magnetic (rTMS) stimulation and
      electroencephalography (EEG). Medial cerebellar rTMS, compared to placebo induced
      a significant shift in anterior asymmetry, from left to right dominance in the
      fast (30-50 Hz) EEG spectrum, whereas occipital and lateral cerebellum
      stimulation did not show such an effect. Moreover elevations in mood and
      alertness were reported again after medial cerebellar stimulation only. Taken
      together, these data confirm and further specify the assumed cerebellar
      modulation of PFC activity and affect.

PMID- 12499044
TI  - Increased RNA levels of the 25 kDa synaptosomal associated protein in brain
      samples of adult patients with Down Syndrome.
AB  - The synaptosomal associated protein of 25kDa (SNAP-25) is widely distributed in
      the brain and reduced in neurodegenerative diseases. In a previous paper we have
      shown reduced amounts of SNAP-25 protein in adult Down Syndrome (DS) brain.
      Neuronal cell death and downregulation at the transcriptional level may be
      responsible for the decrease. Therefore SNAP-25 mRNA levels were determined in
      frontal cortex and cerebellum of adult DS by a competitive reverse transcription
      polymerase chain reaction. We found significantly increased mRNA levels in DS
      either related to 10 ng total RNA (P < 0.05 level in cerebellum: DS 2622 +/- 1081
      attogr mean +/- SEM and controls 154 +/- 37 attogr. mean +/- SEM) or normalized
      versus the house keeping gene beta-actin (P < 0.05 level in frontal cortex: DS
      1324 +/- 504 attogr. mean +/- SEM and control 131 +/- 32 attogr. mean +/- SEM;
      P<0.01 in cerebellum: DS 632 +/- 189 attogr. mean +/- SEM and control 21 +/- 2
      attogr. mean +/- SEM). The main finding of this study shows elevated mRNA levels
      of SNAP-25 in adult DS brain whereas histological and protein-chemical evidence
      for decreased synaptosomal structures including SNAP-25 in a comparable cohort
      has been reported. We suggest compensatory mechanisms for the upregulation at the
      transcriptional level. We propose that SNAP-25 as many other brain proteins are
      regulated by protein stability rather than at the mRNA level.

PMID- 12499045
TI  - Light-dependent development of asymmetry in the ipsilateral and contralateral
      thalamofugal visual projections of the chick.
AB  - Light-exposure of the chick embryo induces development of asymmetry in the
      thalamofugal visual projections to the Wulst regions of the forebrain since the
      embryo is turned so that it occludes its left and not its right eye. This
      asymmetry can be reversed by occluding the embryo's right eye and exposing its
      left eye to light. Here we show that three sub-regions of the thalamus (two in
      the dorsolateral anterior thalami (DLA) and one more caudal) have differing
      asymmetries of contralateral and/or ipsilateral projections. Hence the effect of
      asymmetrical light stimulation is regionally specific within the thalamus.
      Lateralised light stimulation appears to promote the development of ipsilateral
      projections from DLA pars dorsolateralis pars anterioris and contralateral
      projections from the caudal regions (the nucleus superficialis parvocellularis
      especially) but it may suppress the development of contralateral projections from
      the nucleus dorsolateralis anterior thalami pars lateralis rostralis. We also
      show that the light stimulation causes lateralised expression of c-fos and
      receptors for neurotransmitters.

PMID- 12499046
TI  - Repetitive transcranial magnetic stimulation induces different responses in
      different cortical areas: a functional magnetic resonance study in humans.
AB  - Repetitive transcranial magnetic stimulation (TMS) for 1 s at 4 Hz and 150% of
      the individual motor threshold was applied to primary motor cortex and adjacent
      cortical regions where no motor response could be produced. The hemodynamic
      reaction was measured using an event-related functional magnetic resonance setup.
      While all volunteers showed a typical signal increase beneath the coil during
      motor cortex stimulation, no consistent signal changes were present during
      frontal or parietal stimulation apart from activation of auditory cortex. The
      results suggest that neuronal stimulation by TMS is followed by an inhibitive
      phase that compensates for the effect of an initial neuronal activation. It is
      further concluded that the signal increases during motor cortex fit a sensory
      feedback from the moving body parts.

PMID- 12499047
TI  - Concentration-dependent dual effect of anandamide on sensory neuropeptide release
      from isolated rat tracheae.
AB  - Most actions of anandamide (AEA) are mediated by the cannabinoid 1 (CB(1))
      receptor activation, but on sensory neurones it is also an agonist on the
      vanilloid subtype 1 receptor (VR(1)). The aim of the present study was to analyse
      the effect of AEA (10(-6)-10(-4) M) on inhibitory CB(1) and excitatory VR(1)
      receptors by measuring sensory neuropeptide release such as somatostatin,
      substance P and calcitonin gene-related peptide, from isolated rat tracheae. AEA
      (10(-6) M) vas without significant effect, 10(-5) M inhibited neuropeptide
      release, which was abolished by the G protein-coupled receptor blocker pertussis
      toxin (100 ng/ml) and the CB(1) receptor antagonist SR141716A (5x10(-7) M). High
      concentrations of AEA (5x10(-5) M, 10(-4) M) increased the release of the
      peptides and this inhibition was prevented by the competitive VR(1) antagonist
      capsazepine (10(-5) M). These results indicate a dual, concentration-dependent
      action of AEA on CB(1) receptors and VR(1) on peripheral sensory nerve terminals.

PMID- 12499048
TI  - Transforming growth factor-beta-inducible gene-h3 (beta(ig)-h3) promotes cell
      adhesion of human astrocytoma cells in vitro: implication of alpha6beta4
      integrin.
AB  - Beta(ig)-h3 is a secretory protein that is induced by transforming growth factor
      (TGF)-beta. We have recently found that beta(ig)-h3 expression is induced in
      cultured astrocytes by TGF-beta1 and in rat cerebral cortex by stab wound. The
      purpose of this study was to examine the effect of the secreted beta(ig)-h3 on
      cell adhesion of astrocytes and the underlying mechanisms. When U87 human
      astrocytoma cells were seeded on dishes coated with recombinant beta(ig)-h3, cell
      adhesion was significantly enhanced. Blocking experiments using various
      antibodies to the integrin subunit suggested alpha6beta4 integrin could be
      involved in the beta(ig)-h3-mediated astrocyte cell adhesion. Cell adhesion to
      beta(ig)-h3 substrate was substantially blocked by preincubation with the
      inhibitor to the src kinase. When cells were plated on beta(ig)-h3-coated dishes,
      tyrosine phosphorylation of focal adhesion kinase was prominently increased
      within 20 min in a beta4 integrin-dependent manner. The results suggest that
      alpha6beta4 integrin-mediated interactions of astrocytes with beta(ig)-h3
      transduce intracellular signals through the focal adhesion proteins, which may
      regulate certain aspects of astrocyte response to brain injury.

PMID- 12499049
TI  - Solubilization and immunological identification of presynaptic alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat hippocampus.
AB  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have
      been identified mostly as postsynaptic receptors mediating fast glutamatergic
      synaptic transmission. However, neurochemical studies based on the modulation of
      neurotransmitter release have suggested the existence of presynaptic AMPA
      receptors. We have used a recently described technique that allows a high-purity
      fractionation of the pre- and postsynaptic proteins of synaptic junctions to
      evaluate the distribution of the different AMPA receptor subunits in rat
      hippocampal synapses. Surprisingly, we found very high levels of GluR1- and
      GluR2/3-like immunoreactivity in the presynaptic fraction, but also in the
      postsynaptic and extrasynaptic fractions. GluR4-like immunoreactivity was much
      less abundant but was still detected, predominantly in the postsynaptic fraction.
      This methodology appears to be far more sensitive than the classical immunogold
      electron microscopy to determine the localization of synaptic receptors.

PMID- 12499050
TI  - A polymorphism in the complement component C1r is not associated with sporadic
      Alzheimer's disease.
AB  - A growing body of evidence suggests that Alzheimer's disease (AD) is associated
      with local inflammation processes. Complement activation is one of the cardinal
      pathological features of the inflammation. Intensive AD association studies
      investigating polymorphisms in inflammatory-related genes have been recently
      performed, mainly in cytokines, but much less has been focused on AD association
      with polymorphisms in complement components. We performed a case-control
      association study between the codon 135 polymorphism in the complement component
      C1r gene and sporadic AD. No association was detected with AD: neither as a risk
      factor, and nor as a modifier gene affecting the age at disease onset and disease
      progression. No interactive effect was found with apolipoprotein E e4. These
      findings show no evidence for association between C1r codon 135 polymorphism and
      AD in our population.

PMID- 12499051
TI  - Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and
      serum from patients with Parkinson's disease.
AB  - In order to investigate the possible role of oxidative RNA damage in the
      pathogenesis of Parkinson's disease (PD), the concentrations of the oxidative
      stress marker 8-hydroxyguanosine (8-OHG) were measured in the cerebrospinal fluid
      (CSF) and the serum of patients with PD and control subjects. The concentration
      of 8-OHG in CSF in PD patients was approximately three-fold that in controls (P <
      0.001). The concentration of 8-OHG in CSF decreased significantly with the
      duration of disease (r(s) = -0.46, P < 0.05). However, the concentration of 8-OHG
      in serum was not significantly altered in PD patients compared to that in
      controls. In addition, the concentration of 8-OHG in CSF showed no correlation
      with that in serum in both the controls and PD patients suggesting that the 8-OHG
      concentrations in the CSF do not reflect those in serum and may be probably
      reflect those in brain tissue. These in vivo findings suggest a possible role of
      8-OHG and increased oxidative RNA damage in the early stage of the development of
      PD.

PMID- 12499052
TI  - Noxious visceral inputs enhance cutaneous tactile response in rat thalamus.
AB  - The current study investigates whether visceral nociceptive inputs affect tactile
      processing in the thalamic ventroposterior lateral nucleus in anesthetized rats
      by means of extracellular single unit recordings. Twenty out of the 44 neurons
      had their response to tactile stimulation increased by preceding nociceptive
      colorectal distension (CRD), and this influence appear more potent than the
      opposite effect, tactile on CRD response. There was a dynamic change of tactile
      response along with CRD response and the background activities as a function of
      repeated colorectal stimulation. The abnormal neuronal discharge in response to
      tactile stimulation in the condition of visceral nociception could contribute to
      the development of referred pain and allodynia.

PMID- 12499053
TI  - Trigeminal antinociception induced by bicuculline in the periaqueductal gray
      (PAG) is not affected by PAG P/Q-type calcium channel blockade in rat.
AB  - We have recently shown that injection of the P/Q-type (Ca(v)2.1/alpha(1A))
      calcium channel blocker, omega-agatoxin IVA, into the periaqueductal gray (PAG)
      facilitates meningeal dural stimulation-evoked trigeminal nociceptive processing.
      We injected the GABA(A) antagonist bicuculline into the PAG in addition to the
      agatoxin and observed bicuculline's effect on neurons responding to dural
      stimulation recorded in the trigeminal nucleus caudalis of rats in order to
      determine if P/Q channel-mediated changes acted through GABAergic mechanisms. The
      inhibition of trigeminal nociceptive neurons characteristic of bicuculline
      administered into the PAG was maintained in the presence of blocked PAG P/Q-type
      calcium channels. This suggests the PAG descending pain modulatory pathway is not
      affected by P/Q-type calcium channel blockade at the postsynaptic GABAergic
      inhibitory interneuron and the facilitation produced by agatoxin is mediated by
      another mechanism. These findings have implications for disorders involving the
      PAG or P/Q-type channels, such as migraine, in particular for the development of
      preventative treatments, suggesting GABAergic and voltage-gated calcium channels
      could be separately modulated.

PMID- 12499054
TI  - Attenuation of mechanical hyperalgesia following spinal cord injury by
      administration of antibodies to nerve growth factor in the rat.
AB  - Spinal cord injury (SCI) often leads to central pain syndrome including
      hyperalgesia to mechanical stimulation. Since there is evidence that nerve growth
      factor (NGF) contributes to pain-related behaviors, we wished to determine if
      anti-NGF might inhibit abnormal somatosensory behaviors that develop following
      SCI in rats. SCI was performed in male Sprague-Dawley rats by T13 spinal
      hemisection. After spinal hemisection, animals were untreated or treated daily
      with anti-NGF or saline intraperitoneally for 10 days. In groups of both
      hemisection only and hemisection with saline treatment, mechanical hyperalgesia
      developed in both hindlimbs, as evidenced by a decrease in paw withdrawal
      thresholds. Mechanical responsiveness of wide dynamic range (WDR) neurons on both
      sides of spinal cord also increased. The anti-NGF treated group demonstrated
      significant suppression of both mechanical hyperalgesia and increased WDR
      neuronal responsiveness. These results indicate that anti-NGF prevents the
      development of abnormal somatosensory behavior and suggest a potential pre
      emptive analgesic treatment for central pain.

PMID- 12499055
TI  - CaM kinase II-alpha activity, levels and Ca/calmodulin dependent phosphorylation
      of substrate proteins in mice brain during fatal murine cerebral malaria.
AB  - The activity and levels of CaM kinase II-alpha was investigated in the cytosolic
      and membrane fraction of mice cerebral cortex and cerebellum using an
      experimental model of fatal murine cerebral malaria (FMCM). In parallel,
      Ca(2+)/Calmodulin dependent phosphorylation of target substrate proteins was
      studied using syntide-2 as substrate. Pathology of FMCM resulted in decreased CaM
      kinase-II activity in both cortex and cerebellum though western analysis revealed
      no appreciable changes in the levels of CaM kinase-II alpha in cytosol and
      membrane fractions from control and cerebral malaria infected brain. Given the
      abundant expression of Cam kinase-II in neuronal tissue, its significance in
      neurotransmitter release and synthesis and signal transduction during apoptosis,
      decreased levels of enzyme activity and altered phosphorylation of substrate
      proteins by CaM kinase II may serve as important cues in understanding the CaM
      kinase signal transduction events central to neurological disorders during FMCM.

PMID- 12499056
TI  - Upregulation of phospholipase D1 in the spinal cords of rats with clip
      compression injury.
AB  - This study examined phospholipase D 1 (PLD1) expression in the central nervous
      system following clip compression spinal cord injury (SCI) in Sprague-Dawley
      rats. After inducing SCI with a vascular clip, the expression of PLD1 in the
      affected spinal cord was analyzed by Western blot and immunohistochemistry.
      Western blot analysis showed that the expression of PLD1 gradually increased in
      the spinal cord on days 0.5, 1, 2, and 4 post injury. Immunohistochemistry showed
      that some cells, including neurons, astrocytes, and some inflammatory cells, were
      positive for PLD1 in the lesions at days 1 and 2 post injury. At day 4, the
      number of PLD1-positive cells in SCI lesions increased, largely matching the
      increases in ED1-positive macrophages and glial fibrillary acidic protein
      positive astrocytes. At this time, macrophages expressed proliferating cell
      nuclear antigen in addition to PLD1. These results suggest that PLD1 expression
      is increased in injured spinal cords, and might be involved in the activation and
      proliferation of macrophages and astrocytes in SCI.

PMID- 12499057
TI  - 1 Hz repetitive transcranial magnetic stimulation of the unaffected hemisphere
      ameliorates contralesional visuospatial neglect in humans.
AB  - The aim of the study was to investigate whether low-frequency repetitive
      transcranial magnetic stimulation (rTMS) over the unaffected hemisphere can
      ameliorate visuospatial neglect. We treated three right brain damaged patients
      with left neglect. 900 pulses (1 Hz frequency) were given over left posterior
      parietal cortex every other day for 2 weeks. Patients performed a computerized
      task requiring length judgement of prebisected lines, tachistoscopically
      presented for 150 ms. With respect to rTMS the task was given 15 days before, at
      the beginning, at the end and 15 days after. At these times patients performed
      also line bisection and clock drawing tasks. rTMS induced a significant
      improvement of visuo-spatial performance that remained quite unchanged 15 days
      after. Patients performance at Time 3 and 4 improved also as concerns line
      bisection and clock drawing tasks.

PMID- 12499059
TI  - Lung cancer screening with low-dose CT.
AB  - Screening for lung cancer is hoped to reduce mortality from this common tumour,
      which is characterised by a dismal overall survival, relatively well defined risk
      groups (mainly heavy cigarette smokers and workers exposed to asbestos) and a
      lack of early symptoms. In the past studies using sputum cytology and chest
      radiography have failed to demonstrate any reduction in lung cancer mortality
      through screening. One of the reasons is probably the relatively poor sensitivity
      of both these tests in early tumours. Low radiation dose computed tomography (CT)
      has been shown to have a much higher sensitivity for small pulmonary nodules,
      which are believed to be the most common presentation of early lung cancer. As,
      however, small pulmonary nodules are common and most are not malignant, non
      invasive diagnostic algorithms are required to correctly classify the detected
      lesions and avoid invasive procedures in benign nodules. Nodule density, size and
      the demonstration of growth at follow-up have been shown to be useful in this
      respect and may in the future be supplemented by contrast-enhanced CT and
      positron emission tomography. Based on these diagnostic algorithms preliminary
      studies of low-dose CT in heavy smokers have demonstrated a high proportion of
      asymptomatic, early, resectable cancers with good survival. As, however, several
      biases could explain these findings in the absence of the ultimate goal of cancer
      screening, i.e. mortality reduction, most researchers believe that randomised
      controlled trials including several 10000 subjects are required to demonstrate a
      possible mortality reduction. Only then general recommendations to screen
      individuals at risk of lung cancer with low-dose CT should be made. It can be
      hoped that international cooperation will succeed in providing results as early
      as possible.

PMID- 12499060
TI  - Classification, staging and prognosis of lung cancer.
AB  - Lung cancer has increased in incidence throughout the twentieth century and is
      now the most common cancer in the Western World. It has a poor prognosis, only 10
      15% of patients survive 5 years or longer. Outcome is dependent on clinical stage
      and cancer cell type. Lung cancer is broadly subclassified on the basis of
      histological features into squamous cell carcinoma, adenocarcinoma, large cell
      carcinoma and small cell carcinoma. The histopathological type of lung cancer
      correlates with tumour behaviour and prognosis. Staging based on prognosis is
      essential in clinical trials comparing different management strategies, and
      enables universal communication regarding the efficacy of different treatments in
      specific patient groups. The anatomic extent of disease determined either
      preoperatively using imaging supplemented by invasive procedures such as
      mediastinoscopy, and anterior mediastinotomy or following resection are described
      according to the T-primary tumour, N-regional lymph nodes, M-distant metastasis
      classification. The International System for Staging Lung Cancer attempts to
      group together patients with similar prognosis and treatment options. Various
      combinations of T, N, and M define different clinical or surgical-pathological
      stages (IA-IV) characterised by different survival characteristics. Refinements
      in staging based on imaging findings have enabled clinical staging to more
      accurately reflect the surgical-pathological stage and therefore more accurately
      predict prognosis. Recent advances including the use of positron emission
      tomography in combination with conventional staging promises to increase the
      accuracy of staging and therefore to reduce the number of invasive staging
      procedures and inappropriate thoracotomies.

PMID- 12499061
TI  - Staging of non-small cell lung cancer: imaging of intrathoracic disease.
AB  - This article reviews the contribution of diagnostic imaging to the intrathoracic
      staging of non-small cell lung cancer. The principle features of the current
      staging system are discussed along with the relative roles of the various imaging
      modalities in the evaluation of the primary tumour and metastatic disease. The
      emerging role of positron emission tomography with fluorodeoxyglucose (FDG-PET)
      as a clinically useful, potentially cost effective, complementary imaging
      technique is also reviewed.

PMID- 12499062
TI  - Extra-thoracic staging of lung cancer.
AB  - This article reviews the staging of extra-thoracic metastatic lung cancer. The
      imaging strategy, including when to screen as well as the different modalities
      available for different sites of spread of disease are discussed. The emerging
      role of whole body positron emission tomography in screening for metastases is
      also explored.

PMID- 12499063
TI  - Bronchoscopy and surgical staging procedures and their correlation with imaging.
AB  - Bronchoscopy, computed tomography (CT) and surgical staging procedures are
      complimentary methods of investigating patients with lung cancer. CT has been
      shown to be of value prior to bronchoscopy in the investigation of haemoptysis
      and malignancy, with excellent correlation between the detection of disease
      within the large airways on CT and direct visualisation at bronchoscopy. The
      utility of CT has been further increased by the development of multislice
      scanners with the generation of volumetric data enabling multiplanar image
      acquisition. Additionally the advent of CT co-registered with positron emission
      tomography will play an important role in guiding the choice of surgical staging
      procedures The increasing use of multidisciplinary medical care requires
      radiologists to have a greater understanding of the abilities and limitations of
      both bronchoscopy and surgical staging procedures in evaluating disease
      demonstrated on imaging.

PMID- 12499064
TI  - Value of FDG-PET in the management of non-small cell lung cancer.
AB  - In the past 5 years, metabolic imaging with positron emission tomography (PET)
      using 18F-fluoro-2-deoxy-glucose (FDG) has become an important imaging modality
      in lung cancer patients. FDG-PET consistently proved to be superior to structure
      based imaging modalities in both the diagnosis and staging of lung cancer. At
      this moment the use of FDG-PET in these indications needs further validation in
      multi-centre large-scale randomised studies, focusing mainly on treatment outcome
      parameters, survival and cost-efficacy. More recently, interesting findings have
      also been reported in the response assessment to cytotoxic treatments providing
      information of greater prognostic significance than can be obtained using
      conventional approaches. This review focuses on the potential role of FDG-PET in
      the diagnosis of lung nodules and masses, and in locoregional and extrathoracic
      staging of non-small cell lung cancer. Emphasis is put on the potential clinical
      implementation of the numerous data of the last decade.

PMID- 12499065
TI  - Percutaneous biopsy in lung cancer.
AB  - This paper presents current indications, contraindications, technical aspects,
      complications and yield of diagnosis of percutaneous lung biopsy in the setting
      of lung cancer. Percutaneous lung biopsy should be performed each time that the
      therapeutic strategy can be significantly influenced, when the procedure is
      technically feasible and to patients for which the benefits outweigh the risks,
      that are pneumothorax and pulmonary haemorrhage. Factors identified as
      potentially favouring post-biopsy pneumothorax are numerous whereas the use of a
      needle size larger than 18 gauge is the major risk factor of bleeding. Although a
      coaxial system is highly suitable in any case, two categories of needles can be
      used; those providing aspiration and those for core biopsies. Both offer similar
      yields for the diagnosis of malignancy, but core biopsies are more efficient for
      the specific diagnosis of benignity and lymphoma. Technical improvements of
      guidance, needle design and pathological techniques may contribute to lower the
      size limit of the nodule to be biopsied, to decrease the complication rate and
      their severity and to increase the yield of diagnosis.

PMID- 12499066
TI  - The solitary pulmonary nodule.
AB  - The solitary pulmonary nodule will be found increasingly by the use of newer
      imaging techniques, including computed tomography (CT) screening. The aim must be
      to have an approach that avoids unnecessary surgery or biopsy with their
      attendant risks. Plain films characterisation, CT assessment, including
      densitometry and enhancement, and growth patterns are discussed and evaluated.
      The use of Bayes theorem to guide these assessment strategies is also described.

PMID- 12499067
TI  - Resolution of limbic encephalitis with detection and treatment of lung cancer:
      clinical-radiological correlation.
AB  - Paraneoplastic limbic encephalitis may develop in the setting of an otherwise
      occult malignancy. In the case reported here, the neuropsychiatric syndrome
      resolved with treatment of the underlying, previously undiagnosed small-cell lung
      cancer, and MR imaging showed resolution of the characteristic temporal lobe
      signal abnormalities.

PMID- 12499068
TI  - In vitro antimicrobial activity of ethanol and water extracts of Cassia alata.
AB  - Crude ethanol and water extract of leaves and barks from Cassia alata were tested
      in vitro against fungi, (Aspergillus fumigatus and Microsporum canis), yeast
      (Candida albicans) and bacteria (Staphylococcus aereus and Escherichia coli). C.
      albicans showed concentration-dependent susceptibility towards both the ethanol
      and water extracts from the barks, but resistant towards the extracts of leaves.
      The degree of susceptibility varied, the water extract from barks showed bigger
      inhibition zone than the ethanol extracts (12-16 and 10-14 mm, diameter
      respectively). The growth of Aspergillus fumigatus and Microsporum canis were not
      affected by all types of the plant extracts. Results were comparable to standard
      antifungal drug Tioconazole (18 mm diameter) at equivalent concentration. The
      anti-bacterial activity of C. alata extracts on S. aureus was detected with only
      the leaves extracts using water and ethanol. The water extract exhibited higher
      antibacterial activity than the ethanol extract from leaves (inhibition zones of
      11-14 and 9-11 mm, respectively). E. coli showed resistance to all types of
      extracts. Based on the current findings, it can be concluded that this plant has
      antimicrobial activity, which is as potent as standard antimicrobial drugs
      against certain microorganisms.

PMID- 12499069
TI  - Pharmacokinetic analysis of rhein in Rheum undulatum L.
AB  - This research aims to identify the main active compounds of Rhei undulati Rhizoma
      (roots of Rheum undulatum LINNE) and determine the types of anthraquinones
      absorbed into the body and their pharmacokinetic parameters. The boiling-water
      extract of the herb was administered to 12 healthy volunteers (9 men/3 women) at
      a dosage of 100 mg/kg the anthraquinone levels in plasma were determined with
      TLC, HPLC, and LC-MS. Rhein was the only anthraquinone compound absorbed by the
      body as determined for plasma analysis of the volunteers. The elimination rate
      constant of rhein in Rhei undulati Rhizoma was 0.23+/-0.02/h and the half life
      was 3.38+/-0.35 h. This experiment confirmed that rhein is the most important
      active compound absorbed by the body among anthraquinones contained in Rhei
      undulati Rhizoma, indicating that rhein is a promising marker substance to
      evaluate Rhei Rhizoma and Rhei undulati Rhizoma.

PMID- 12499070
TI  - Evaluation of anti-diarrhoeal activity in seed extracts of Mangifera indica.
AB  - Mangifera indica is commonly grown in many parts of the world. Its seeds have
      been used for anti-diarrhoeal activity in Indian traditional medicine. This study
      evaluates the potential anti-diarrhoeal activity of methanolic (MMI) and aqueous
      (AMI) extracts of seeds of M. indica in experimental diarrhoea, induced by castor
      oil and magnesium sulphate in mice. Both MMI and AMI were given orally in the
      dose of 250 mg/kg, showed significant anti-diarrhoeal activity comparable with
      that of the standard drug loperamide. However, only MMI significantly reduced
      intestinal transit in charcoal meal test as compared with atropine sulphate (5
      mg/kg; im). The in vitro antimicrobial activity of MMI and AMI showed variable
      results. While, AMI significantly inhibited growth of Streptococcus aureus and
      Proteus vulgaris, both MMI and AMI did not show any significant effect on growth
      of E. coli and Klebsiella. The results illustrate that the extracts of M. indica
      have significant anti-diarrhoeal activity and part of the activity of MMI may be
      attributed to its effect on intestinal transit.

PMID- 12499071
TI  - Anti-inflammatory and analgesic properties of the stem bark extract of Mitragyna
      ciliata (Rubiaceae) Aubrev. & Pellegr.
AB  - Mitragyna ciliata is widely used in traditional medicine for the treatment of
      inflammation, hypertension, headache, rheumatism, gonorrhoea and broncho
      pulmonary diseases. In the present study, the anti-inflammatory and analgesic
      properties of the stem bark extract of M. ciliata were investigated. The stem
      bark of this plant was extracted over Soxhlet with hexane followed by another
      extraction with methanol. The resulting methanol extract was used for the
      pharmacological test. Anti-inflammatory activity was evaluated on the basis of
      the inhibitory effect of the extract on 5-lipoxygenase, and carrageenin-induced
      hind paw oedema in the rat. The methanol extract, at a dose of 19.2 microg/ml,
      exhibited no inhibition on 5-lipoxygenase. However, this extract administered per
      os (50 mg/kg) produced about 70% inhibition of carrageenin-induced paw oedema 1 h
      after administration. This inhibition was maintained to about 50% 2 h after
      administration. The dose of 50 mg/kg of MeOH extract significantly decreased
      sensitivity to pain from 78.75 to 107.5 g These findings suggest that extracts of
      the bark of M. ciliata, possess potent anti-inflammatory and analgesic effects.
      Chemical analysis of the extract showed the presence of alkaloids and kaempferol
      derivative which may be responsible for the anti-inflammatory properties.

PMID- 12499072
TI  - Effects of wogonin, wogonoside, and 3,5,7,2',6'-pentahydroxyflavone on chemical
      mediator production in peritoneal exduate cells and immunoglobulin E of rat
      mesenteric lymph node lymphocytes.
AB  - Wogonin (WG), wogonoside (WGS), and 3,5,7,2',6'-pentahydroxyl flavanone (PHF)
      were isolated from Scutellaria baicalensis, and their effects on histamine,
      leukotriene B(4) (LTB(4)), and immunoglobulin E (IgE) were examined in rats,
      observing for a manifestation of a type I allergic reaction. WG and WGS in the
      amounts of 10 and 100 microM were shown to markedly inhibit histamine release in
      cells stimulated with calcium ionophore A23187 or compound 48/80. PHF exerted
      inhibitory activity only at 100 microM. In the case of LTB(4), WG, WGS and PHF
      markedly inhibited LTB(4) production at the concentration of 100 microM. We also
      find that the increase in the IgE content induced by concanavalin A (ConA) was
      alleviated in the presence WG and WGS, while the inhibitory effect of PHF was
      much weaker. However, the magnitude of inhibitory effect observed on the content
      of lipid peroxidation induced by ConA was in order of PHF > WG > WGS, with PHF
      being the strongest. Interestingly, WG and WGS with the methoxyl group strongly
      inhibited histamine and IgE production, whereas PHF with the hydroxyl group in
      the B ring was much stronger than WG and WGS against lipid peroxidation. Based on
      data, it was concluded that the flavonoid components, WG, WGS, and PHF, may block
      a common pathway for the release of histamine and LTB(4), and that the IgE level
      is responsible for the lipid peroxidation induced by ConA.

PMID- 12499073
TI  - Anti-inflammatory, antipyretic and antinociceptive activities of Tabernaemontana
      pandacaqui Poir.
AB  - Studies on carrageenin-induced rat paw edema, yeast-induced hyperthermia in rat
      and writhing response induced by acetic acid in mice showed that the alcoholic
      extract of stems of Tabernaemontana pandacaqui (T. pandacaqui) has significant
      anti-inflammatory, antipyretic and antinociceptive activities. These activities
      are due to alkaloidal components since they were also observed when the crude
      alkaloidal (CA) fraction separated from alcoholic extract was tested in the same
      models.

PMID- 12499074
TI  - Ethnomedicobotany of Uttara Kannada District in Karnataka, India--plants in
      treatment of skin diseases.
AB  - Present paper deals with the herbal remedies for skin diseases in Uttara Kannada
      district of Karnataka--a Southern State in India, which is located in the hearts
      of Western Ghats. In an ethnobotanical exploration of this area 52 herbal
      preparations from 31 plants belonging to 21 families have been recorded. This
      also includes 17 new claims to the ethnomedical knowledge. The parts used and
      methods of preparation are discussed along with the family and local name for all
      the plants.

PMID- 12499075
TI  - Advanced studies on the hypoglycemic effect of Caesalpinia bonducella F. in type
      1 and 2 diabetes in Long Evans rats.
AB  - Caesalpinia bonducella, widely distributed throughout the coastal region of India
      and used ethnically by the tribal people of India for controlling blood sugar was
      earlier reported by us to possess hypoglycemic activity in animal model. This
      prompted us to undertake a detail study with the aqueous and ethanolic extracts
      of the seeds of this plant in both type 1 and 2 diabetes mellitus in Long Evans
      rats. Significant blood sugar lowering effect (P < 0.05) of C. bonducella was
      observed in type 2 diabetic model. Special emphasis was given on the mechanistic
      study by gut absorption of glucose and liver glycogen.

PMID- 12499076
TI  - Liv.52 in alcoholic liver disease: a prospective, controlled trial.
AB  - Liv.52, a hepatoprotective agent of herbal origin, is used empirically for the
      treatment of alcoholic liver disease in Sri Lanka. We conducted a controlled
      trial to assess the efficacy of Liv.52 in patients with alcoholic liver disease.
      Patients with evidence of alcoholic liver disease attending outpatient clinics
      were included in a prospective, double blind, randomized, placebo controlled
      trial. During the trial period, 80 patients who fulfilled inclusion criteria were
      randomly assigned Liv.52 (cases; n = 40) or placebo (controls) the recommended
      dose of three capsules twice daily for 6 months. All patients underwent clinical
      examination (for which a clinical score was computed), and laboratory
      investigations for routine blood chemistry and liver function before commencement
      of therapy (baseline). Thereafter, clinical assessments were done monthly for 6
      months, while laboratory investigations were done after 1 and 6 months of
      therapy. There was no significant difference in the age composition, alcohol
      intake and baseline liver function between the two groups. The two-sample t-test
      was used to analyze data obtained after 1 and 6 months of therapy against
      baseline values. There was no significant difference in clinical outcome and
      liver chemistry between the two groups at any time point. There were no reports
      of adverse effects attributable to the drug. Our results suggest that Liv.52 may
      not be useful in the management of patients with alcohol induced liver disease.

PMID- 12499077
TI  - Effect of the rhizomes of Atractylodes lancea and its constituents on the delay
      of gastric emptying.
AB  - The effect of rhizomes of Atractylodes lancea on gastric disorders, in
      particular, the delay in gastric emptying induced by N(G)-nitro-L-arginine in
      rats, was investigated. Intragastric treatment with an aqueous extract (250
      mg/kg) and its lipophilic fractions (4 mg/kg) significantly improved delayed
      gastric emptying. The major constituents of the lipophilic fraction were two
      sesquiterpens, hinesol and beta-eudesmol, and four known polyacetylenic
      compounds, atractylodin, atractylodinol, acetylatractylodinol and 4,6,12
      tetradecatriene-8,10-diyne-1,3,14-triol. The activity was found in the four
      polyacetylenic compounds at a similar potency, but not in the two sesquiterpens.
      To clarify the effect of the four polyacetylenic compounds in this extract, we
      attempted to evaluate the activity of atractylodin, as representative, at a dose
      of 0.2 mg/kg based on the total amounts (0.2 mg/250 mg aqueous extract) of the
      four polyacetylenic compounds. In addition, atractylodin improved the delay in
      gastric emptying at between 0.1 and 0.3 mg/kg in a dose-dependent manner. These
      results suggest that the aqueous extract improved the delayed gastric emptying,
      and polyacetylenic compounds contributed to its activity.

PMID- 12499078
TI  - Traditional herbal drugs of Southern Uganda, II: literature analysis and
      antimicrobial assays.
AB  - Continuing field interviews brought the total species used for disease treatment
      by herbalists of the majority Baganda Tribe of southern Uganda to 168. Literature
      searches provided support for the ethnomedical claims for a number of these
      species, and provided criteria for the species classification into four
      categories of use validation. They also helped guide the selection of species for
      recollection, for chemical extraction and further testing in laboratories of the
      Uganda Ministry of Health and the University of Illinois at Chicago. Many species
      proved active against microorganisms in several susceptibility assays conducted
      in Uganda and the US.

PMID- 12499079
TI  - The Maasai ethnodiagnostic skill of livestock diseases: a lead to traditional
      bioprospecting.
AB  - A survey study was conducted on the ethnoveterinary knowledge of the Ilkisonko
      Maasai of Kenya. The data on the ethnodiagnostic skills of livestock diseases was
      gathered using a well-structured questionnaire. The result show that the Maasai
      rely not only on symptoms of diseases but also on vectors of disease, season
      effects and species affected by a particular malady. The Ilkisonko Maasai use 18
      medicinal plant species to combat the diseases positively diagnosed. It is
      concluded that, the Maasai ethnodiagnostic skill is the bases of their
      traditional bioprosecting techniques.

PMID- 12499080
TI  - Inhibitory effects of the root cortex of Paeonia suffruticosa on interleukin-8
      and macrophage chemoattractant protein-1 secretions in U937 cells.
AB  - In an effort to elucidate the mechanism of the anti-inflammatory effect of
      mudanpi, the root cortex of Paeonia suffruticosa Andrews (Ranunculaceae), we
      determined the effects of the methanolic extract of mudanpi (MEM) on the
      secretions of interleukin (IL)-8, a major mediator of acute neutrophil-mediated
      inflammation, and macrophage chemoattractant protein (MCP)-1, a major mediator of
      chronic macrophage-mediated inflammation, in human monocytic U937 cells
      stimulated with phorbol myristate acetate (PMA). MEM significantly inhibited PMA
      induced secretions of IL-8 and MCP-1 proteins in a dose-dependent manner. The
      inhibition of these chemokines by MEM was due to its suppression of IL-8 and MCP
      1 genes. In addition, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, one of major
      constituents isolated from MEM, inhibited PMA-induced secretions of IL-8 and MCP
      1 proteins by its suppression of IL-8 and MCP-1 genes. Thus, one possible anti
      inflammatory mechanism of mudanpi, an anti-inflammatory Chinese crude drug, may
      be to inhibit the secretions of inflammatory chemokines.

PMID- 12499081
TI  - The effects of aqueous extract of Lavandula angustifolia flowers in glutamate
      induced neurotoxicity of cerebellar granular cell culture of rat pups.
AB  - In the present study, neuroprotective effect of Lavandula angustifolia flower
      aqueous extract in glutamate-induced neurotoxicity in rat pups cerebellar
      granular cell culture was investigated. The extract at doses of 10 microg ml(-1),
      100 microg ml(-1), 1 mg ml(-1) and 10 mg ml(-1) was applied to culture flasks.
      The extract at doses of 100 microg ml(-1) and 1 mg ml(-1) significantly blocked
      glutamate-induced neurotoxicity, with the most effective dose being 1 mg ml(-1).
      On the other hand, 10 mg ml(-1) dose of extract increased the dead cell with
      respect to glutamate group, despite being found insignificant statistically. As a
      result, L. angustifolia protected the neurons against glutamate toxicity.

PMID- 12499082
TI  - Ethyl ether fraction of Gastrodia elata Blume protects amyloid beta peptide
      induced cell death.
AB  - Alzheimer's disease is the most common cause of dementia in the elderly.
      Recently, it has been reported that Alzheimer's disease is associated with cell
      death in neuronal cells including the hippocampus. Amyloid beta-peptide
      stimulates neuronal cell death, but the underlying signaling pathways are poorly
      understood. In order to develop anti-dementia agents with potential therapeutic
      value, we examined the effect of the herbal compound Gastrodia elata Blume (GEB)
      on neuronal cell death induced by amyloid beta-peptide in IMR-32 neuroblastoma
      cells. The fractionation of GEB was carried out in various solvents. The hydroxyl
      radical scavenging effect of the ethyl ether fraction was more potent than any
      other fractions. In cells treated with amyloid beta-peptide, the neuroprotective
      effect of the ethyl ether, chloroform, and butanol fractions was 92, 44, and 39%,
      respectively, compared with control. Taken together, these results suggest that
      the ethyl ether fraction of GEB contains one or more compounds that dramatically
      reduce amyloid beta-peptide induced neuronal cell death in vitro.

PMID- 12499083
TI  - Antifertility activity of Derris brevipes variety coriacea.
AB  - Traditional physicians in and around Kotagiri village near Ootacamund, use a
      mixture of powdered roots of Cassia occidentalis, Derris brevipes variety
      coriacea and Justicia simplex to control female fertility. A mixture of powdered
      roots of these three plants, powdered root of Derris brevipes variety coriacea
      and its ethanolic extract were screened for antifertility activity in proven
      fertile female rats at 200 and 600 mg/kg body weight, respectively and given
      orally on D(1-7) of pregnancy. Both doses of the root powder of Derris brevipes
      variety coriacea showed 50% anti-implantation activity and also a significant
      reduction in the number of litters born. The ethanolic extract exhibited 40% anti
      implantation activity when given orally at 600 mg/kg body weight. The rats, which
      continued their pregnancy, did not deliver any litters after their full term.
      Hence, the combined antifertility (anti-implantation and abortifacient) activity
      of the ethanolic extract was 100%. The results suggest that the ethanolic extract
      possesses more abortifacient type effect than the anti-implantation activity. The
      ethanolic extract also exhibited weak estrogenic activity when given alone and
      tested in immature ovariectomised female albino rats. But, when given along with
      ethinyl estradiol, it exhibited slight antiestrogenic activity. Histological and
      biochemical estimations were carried out to confirm this.

PMID- 12499084
TI  - Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants
      in alloxan diabetic rats.
AB  - In our experiments 30 hypoglycaemic medicinal plants (known and less known) have
      been selected for thorough studies from indigenous folk medicines, Ayurvedic,
      Unani and Siddha systems of medicines. In all the experiments with different
      herbal samples (vacuum dried 95% ethanolic extracts), definite blood glucose
      lowering effect within 2 weeks have been confirmed in alloxan diabetic albino
      rats. Blood glucose values are brought down close to normal fasting level using
      herbal samples at a dose of 250 mg/kg once, twice or thrice daily, as needed.
      While evaluating comparative hypoglycaemic activity of the experimental herbal
      samples, significant blood glucose lowering activities are observed in decreasing
      order in the following 24 samples-Coccinia indica, Tragia involucrata, G.
      sylvestre, Pterocarpus marsupium, T. foenum-graecum, Moringa oleifera, Eugenia
      jambolana, Tinospora cordifolia, Swertia chirayita, Momordica charantia, Ficus
      glomerata, Ficus benghalensis, Vinca rosea, Premna integrifolia, Mucuna prurita,
      Terminalia bellirica, Sesbenia aegyptiaca, Azadirachta indica, Dendrocalamus
      hamiltonii, Zingiber officinale, Aegle marmelos, Cinnamomum tamala, Trichosanthes
      cucumerina and Ocimum sanctum. Present studies besides confirming hypoglycaemic
      activities of the experimental herbal samples, help identify more potent
      indigenous hypoglycaemic herbs (in crude ethanolic extract) from the comparative
      study of the reported experimental results.

PMID- 12499085
TI  - Investigations into the immunomodulatory activity of Argyreia speciosa.
AB  - The objective of the present study was to investigate the immunomodulatory
      activity of Argyreia speciosa on cellular and humoral immunity. Oral
      administration of the ethanolic extract of A. speciosa root (ASEE), at the doses
      of 50, 100 and 200 mg/kg in mice, dose-dependently potentiated the delayed-type
      hypersensitivity reaction induced both by sheep red blood cells (SRBC) and
      oxazolone. It significantly enhanced the production of circulating antibody titre
      in mice in response to SRBC. ASEE failed to show any effect on macrophage
      phagocytosis. Chronic administration of ASEE significantly ameliorated the total
      white blood cell count and also restored the myelosuppressive effects induced by
      cyclophosphamide. The present investigation reveals that ASEE possesses
      immunomodulatory activity.

PMID- 12499086
TI  - Components of Panax ginseng that improve accelerated small intestinal transit.
AB  - We previously clarified that Dai-kenchu-to, a Chinese prescription, was useful
      for improving carbachol-induced hyperperistalsis of the small intestine in vivo,
      and the efficacy of Ginseng Radix, a crude drug component of Dai-kenchu-to, was
      also confirmed. Ginseng Radix, the root of Panax ginseng C.A. Meyer, showed
      significant ameliorative effects on both the carbachol-induced and the BaCl(2)
      induced accelerated small intestinal transit model in mice, suggesting that both
      an inhibitory effect on the cholinergic nervous system and direct suppressive
      effect on muscles were involved in the ameliorative effect of Ginseng Radix on
      the accelerated small intestinal transit. Ginsenoside Rb1 (4) and ginsenoside Rd
      (7), major components of Ginseng Radix, improved both animal models. These
      results suggest that ginsenoside Rb1 (4) and ginsenoside Rd (7) were
      representative compounds of Ginseng Radix for improving the accelerated movement
      of the small intestine and that these compounds partly contribute to the action
      of Dai-kenchu-to on small intestinal transit.

PMID- 12499088
TI  - Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non
      small cell lung cancer: potential targets for chemoprevention and systemic
      therapy.
AB  - The epidermal growth factor receptor (EGFR) is part of a family of plasma
      membrane receptor tyrosine kinases that control many important cellular
      functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is
      an enzyme which catalyses the conversion of arachidonic acid to prostagladins and
      thromboxane. It is induced by various inflammatory stimuli, including the pro
      inflammatory cytokines, Interleukin (IL)-1beta, Tumour Necrosis Factor (TNF)
      alpha and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung
      cancer (NSCLC) and have been implicated in the early stages of tumourigenesis.
      This paper considers their roles in the development and progression of lung
      cancer, their potential interactions, and reviews the recent progress in cancer
      therapies that are directed toward these targets. An increasing body of evidence
      suggests that selective inhibitors of both EGFR and COX-2 are potential
      therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and
      chemopreventative settings.

PMID- 12499089
TI  - Expression of antioxidant enzymes in bronchial metaplastic and dysplastic
      epithelium.
AB  - We investigated immunohistochemical expression of manganese superoxide dismutase
      (MnSOD) and three hydrogen peroxide (H(2)O(2)) scavenging pathways, i.e. catalase
      (CAT), gamma-glutamyl cysteine synthetase (gammaGCS) and thioredoxin (Trx) system
      in normal bronchial epithelium, bronchial metaplasia and dysplasia and correlated
      their expression with NF-kappaB activation (p50) and proliferation (Ki67). Normal
      bronchial epithelium was positive for MnSOD, heavy and light subunits of
      gammaGCS, CAT and Trx and TrxR. Metaplastic epithelium showed strongest
      expression of gammaGCSh and Trx, whereas dysplastic epithelium expressed most
      prominently MnSOD and CAT. There was a significant correlation between expression
      of gammaGCSh and gammaGCSl (P=0.034) and Trx and TrxR (P=0.037). Trx expression
      also correlated with gammaGCSh (P<0.001) and gammaGCSl (P=0.012) and TrxR with
      gammaGCSh (P<0.001) but not with gammaGCSl immunoreactivity (P=0.744). Expression
      of p50 was highest in metaplastic epithelium while Ki67 was highest in dysplastic
      lesions. Expression of Trx and gammaGCSh correlated inversely with age of the
      patients (R=-0.6038, P<0.001 for Trx and R=-0.6162, P<0.001 for gammaGCSh).
      Changes in the expression of these enzymes in bronchial lesions might be due to
      alterations of antioxidative mechanisms due to irritation via exogenous toxins
      and activation of reactive oxygen species (ROS) known to be associated with
      induction of metaplasia and dysplasia in the bronchial tree.

PMID- 12499090
TI  - Patterns of allelic loss differ in lung adenocarcinomas of smokers and
      nonsmokers.
AB  - Cigarette smoking is the most important cause of lung cancer, however
      approximately 10% of patients with lung cancer have no history of smoking. While
      the molecular pathogenesis of smoking associated lung carcinogenesis is becoming
      well characterized, the pathogenesis of lung cancer in nonsmokers is not. We
      designed a study to examine the pathogenesis of adenocarcinoma in nonsmokers by
      determining if loss of heterozygosity (LOH) in tumors of nonsmokers differs from
      those of smokers. We evaluated six cases of primary adenocarcinoma in never
      smokers and six selected cases in smokers, matched by clinical and histological
      criteria. LOH in tumor DNA relative to nonmalignant lung DNA was determined at 52
      microsatellites located on ten chromosomal loci. The extent of allelic loss in
      smokers, as measured by fractional allelic loss (FAL), was compared with
      nonsmokers. LOH was more frequent in the tumors of nonsmokers than of smokers
      with mean FAL of 46% in nonsmokers and 28% in smokers (P<0.05). Increased LOH in
      nonsmokers was most pronounced at chromosomes: 3p, 8p, 9p, 10p, and 18q. Since
      this study compared allelic loss between lung and tumor-bearing lung, less
      frequent LOH in smokers' tumors can be interpreted to suggest LOH was already
      present in the nonmalignant lung of smokers and fewer additional instances of
      allelic loss were present in the tumors of smokers. Our results suggest that the
      early steps of lung carcinogenesis differ in nonsmokers compared with smokers. In
      addition, the chromosomal sites of LOH may identify genes important for lung
      carcinogenesis in nonsmokers.

PMID- 12499091
TI  - Expression of thyroid transcription factor-1 in 16 human lung cancer cell lines.
AB  - It has been suggested that thyroid transcription factor-1 (TTF-1) is frequently
      expressed in human lung cancer, especially in adenocarcinoma and small cell lung
      cancer, and the TTF-1 expression is closely related with the expression of
      surfactant protein. We hypothesized that TTF-1 is expressed in human lung cancer
      cell lines and its expression might be related to the expression of surfactant
      protein. To test this, expressions of TTF-1 and surfactant protein A (SP-A) were
      immunohistochemically evaluated in 16 human lung cancer cell lines. In addition,
      expressions of mRNAs for TTF-1 and SP-A were analyzed by reverse transcriptase
      polymerase chain reaction (RT-PCR) and sequencing. As a result, nuclear staining
      of TTF-1 was observed in two of six adenocarcinoma cell lines, none of seven
      small cell lung cancer cell lines, and none of three squamous lung cancer cell
      lines. Among the 16 cell lines, six cell lines (PC3, LC2/Ad, A549, RERF-LC-OK,
      HI1017, and PC9) expressed significant amounts of mRNA for TTF-1. In contrast,
      cytoplasmic staining of TTF-1 was observed in five of six adenocarcinoma cell
      lines, in six of seven small cell lung cancer cell lines, and in all three
      squamous cell lung cancer cell lines. One of the two adenocarcinoma cell lines
      those showed positive nuclear staining and cytoplasmic SP-A staining released a
      significant amount of SP-A in culture supernatant. Our present study demonstrates
      that the frequency of TTF-1 expression in the nucleus was very low in human lung
      cancer cell lines; however, their cytoplasmic positivities should be further
      investigated.

PMID- 12499092
TI  - Comparison of three tracers for detecting sentinel lymph nodes in patients with
      clinical N0 lung cancer.
AB  - The goal of this pilot study was to compare three tracers for the detection of
      sentinel nodes in patients with lung cancer. Forty-eight patients with clinical
      N0 non-small cell lung cancer were enrolled. Indocyanine green (n=16) or
      isosulfan blue (n=18) was injected around the tumor intraoperatively, or
      technetium tin colloid was injected preoperatively under CT guidance (n=14).
      Sentinel nodes were detected in 6.3% of patients injected with indocyanine green,
      50.0% of patients injected with isosulfan blue, and 64.3% of patients injected
      with technetium tin colloid. The detection rate achieved with indocyanine green
      was significantly lower than with the other two tracers. A false-negative
      sentinel node was seen in 1 patient using isosulfan blue. Both isosulfan blue and
      technetium tin colloid seem to be suitable for intraoperative sentinel node
      mapping in patients with lung cancer.

PMID- 12499093
TI  - Relevance of p53, bcl-2 and Rb expression on resistance to cisplatin-based
      chemotherapy in advanced non-small cell lung cancer.
AB  - PURPOSE: Tumors with p53 overexpression have been associated with enhanced
      resistance to cisplatin-based chemotherapy in a few and small studies involving
      non-small cell lung cancer. The relationships and interactions between p53, Rb
      and bcl-2 immunostaining, clinical parameters and response to cisplatin-based
      chemotherapy were evaluated in the present study. EXPERIMENTAL DESIGN:
      Histological specimens obtained by bronchial or fine-needle biopsy from patients
      who underwent cisplatin-based chemotherapy between 1992 and 1999 were evaluated
      by immunostaining. RESULTS: There were 102 patients, 88 men. Median age was 63
      years; 47 had stage III and 55 stage IV disease. Forty-six tumor samples (45%)
      had positive immunostaining for p53, 61 (59%) had negative immunostaining for Rb
      and 8 (8%) had positive immunostaining for bcl-2. The response rate of the group
      with p53 positive immunostaining was 26% versus 57% of the p53 negative group
      (P=0.004). In multivariate analyses p53 positive immunostaining was identified as
      an independent predictive factor for resistance to cisplatin-based chemotherapy
      (P=0.006). CONCLUSIONS: Our study confirmed an association of p53 immunostaining
      and response rate of patients treated with cisplatin-based chemotherapy.

PMID- 12499094
TI  - Bronchoscopic treatment of patients with intraluminal microinvasive
      radiographically occult lung cancer not eligible for surgical resection: a follow
      up study.
AB  - Bronchoscopic treatment (BT) has a curative potential for patients with
      intraluminal microinvasive radiographically occult lung cancer (ROLC). We report
      the long-term follow-up in a group of 32 patients, ineligible for surgery, in
      whom ROLC was diagnosed and treated with BT. Tumors were strictly <or=1 cm in
      size, intraluminally located in the central airways, with no bronchial wall
      invasion or extraluminal tumor growth on high resolution CT (HRCT), with visible
      distal margin under conventional and autofluorescence bronchoscopy (AFB). BT was
      given with curative intent and consecutive patients were treated with
      photodynamic therapy (five patients), Nd-YAG laser therapy (one patient),
      electrocautery (24 patients) and argon plasma coagulation (two patients). Follow
      up evaluation at 3-4 months interval included HRCT scans, both conventional and
      AFB, including biopsies and brush cytology for histological evaluation. The
      average follow-up period was 5 years (range: 2-10 years). In three patients local
      recurrence was again successfully treated with electrocautery. Sixteen patients
      died during follow-up. Eight of the nine patients who died due to lung cancer had
      a previous resection of a more advanced stage lung cancer up to 5 years before BT
      of the ROLC. The remaining seven patients cause of death was not related to lung
      cancer. Sixteen patients are still alive without any tumor recurrence. These data
      showed that BT is an effective treatment modality for high-risk patients with
      ROLC, who are not eligible for surgical resection.

PMID- 12499095
TI  - A retrospective analysis of the outcome of patients who have received two prior
      chemotherapy regimens including platinum and docetaxel for recurrent non-small
      cell lung cancer.
AB  - With the availability of chemotherapy agents for first- and second-line treatment
      of advanced non-small-cell lung cancer (NSCLC), the patient population that
      requires subsequent chemotherapy is increasing. This retrospective analysis was
      performed to describe the clinical course after two standard or approved
      chemotherapy agents in patients with good overall performance status. Data were
      selected from patients with advanced NSCLC who had received third- or fourth-line
      chemotherapy after two prior chemotherapy regimens that included platinum and
      docetaxel given concurrently or sequentially. Prior regiments had failed due to
      discase progression within 90 days of chemotherapy, or unacceptable toxicity.
      Examination of over 700 patient records between January 1993 and January 2000 at
      one US and one European cancer centre revealed 43 patients that fulfilled the
      inclusion criteria. Response rates decreased with each line of treatment: first
      line, 20.9%; second line, 16.3%; third line, 2.3%; and fourth line, 0%. The
      disease control rate (response plus stable disease) also decreased dramatically
      from first- to fourth-line treatment, although it was higher for second-line
      treatment (74.4%) than for first-line treatment (62.8%). The median overall
      survival time from diagnosis was 16.4 months. The median overall survival time
      from the start of the last treatment (either third or fourth line) was 4 months.
      Patients with stage III disease at diagnosis had a longer overall survival from
      diagnosis than patients with stage IV disease (P=0.02). This review highlights
      the need for novel therapy approaches for patients with recurrent NSCLC who have
      failed second-line therapy and provides a baseline for the statistical design of
      such studies.

PMID- 12499096
TI  - Long-term survival in SCLC after treatment with paclitaxel, carboplatin and
      etoposide--a phase II study.
AB  - PURPOSE: We evaluated the toxicity and feasibility of adding paclitaxel to a
      standard platinum/etoposide regimen in the first-line treatment of patients with
      small cell lung cancer (SCLC). PATIENTS AND METHODS: Eighty-nine patients with
      limited disease (LD) or extensive disease without distant metastases (ED I) were
      treated in this multi-centered phase II trial between April 1996 and June 1997.
      Paclitaxel administration (175 mg/m(2) by a 1 h intravenous infusion) was
      immediately followed by a 30 min infusion of carboplatin at an area under the
      concentration time curve (AUC) of 5 on day 1 and etoposide 50 mg orally twice
      daily (bid) was given on days 2-8. Courses were repeated every 21 days. Patients
      who had an objective response continued treatment for a maximum of 6 courses.
      RESULTS: Eighty-four patients were assessable for response. Overall response rate
      (RR) was 82.1% with 17.8% complete remissions and 64.3% partial remissions.
      Median survival for LD patients was 20.5 months with a 1 year survival rate of
      71.4% and a 3 year survival rate of 21.4%. Median survival of ED I patients was
      11 months with a 1 year survival rate of 31.3% and a 3 year survival rate of
      3.1%. Overall median survival was 18.1 months with a 1 year survival rate of
      56.8% and a 3 year survival rate of 14.8%. Median progression-free intervals were
      12.3 months for patients with LD stage of the disease and 8 months with ED I
      stage. Grade 3/4 toxicity was primarily hematologic. Grade 3/4 leucopenia
      occurred in 16.0% of courses and febrile episodes were detected in 0.3% of
      courses. Non-hematologic toxicities were uncommon. Grade 3 GI-tract toxicities or
      peripheral neuropathy appeared in less than 1% of the courses. Toxicities were
      detected according to WHO toxicity criteria. CONCLUSION: Paclitaxel can be added
      at full dose (175 mg/m(2)) to a carboplatin/etoposide combination while
      maintaining a tolerable toxicity profile. Efficacy data, RR, progression-free
      interval and survival in both, extensive and limited stage patients compare
      favorably with other reported data. This new regimen will be further evaluated in
      comparison to standard regimens in a phase III trial.

PMID- 12499097
TI  - Sequential administration of cisplatin-etoposide followed by topotecan in
      patients with extensive stage small cell lung cancer. A multicenter phase II
      study.
AB  - PURPOSE: To evaluate the activity of the sequential administration of cisplatin
      etoposide (PE) followed by topotecan (TOP) in patients with extensive stage small
      cell lung cancer (SCLC). PATIENTS AND METHODS: Previously untreated patients with
      extensive stage SCLC received 4 cycles of cisplatin 75 mg/m(2) IV on day 1 and
      etoposide 100 mg/m(2) IV on days 1-3 every 21 days followed by 4 cycles of TOP
      1.5 mg/m(2) IV on days 1-5 every 21 days. RESULTS: Thirty-eight patients were
      entered in the study. Their median age was 63 years and the performance status
      (WHO) was 0 for 5, 1 for 25 and 2 for 8 patients. All patients were evaluable for
      toxicity and 32 for response to PE and 25 to TOP. Of the 38 patients receiving
      PE, 1 (3%) patient achieved complete response (CR) and 17 (45%) partial responses
      (PR) for an overall response rate to PE of 47% (95% confidence interval: 36.7
      68.5%). Four (23.5%) of the 17 patients with PR after PE, achieved CR with TOP.
      None of the patients with stable or progressive disease after PE responded to
      TOP. The response rate of the 27 patients receiving TOP following PE was 15% (95%
      confidence interval: 1.4-28.2%). After a median follow up of 9 months, the median
      duration of response was 6.5 months, the time to tumor progression 6.5 months,
      the median survival 8.5 months and the 1-year survival 34%. A total of 136 cycles
      of PE and 89 cycles of TOP have been administered with a median of 4
      cycles/patient for each regimen. There were 2 toxic deaths after PE associated
      with grade IV febrile neutropenia. Treatment delays due to toxicity occurred in
      17 (12%) cycles of PE and 20 (22%) cycles of TOP while doses were reduced in 7
      (5%) and 4 (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and
      febrile neutropenia occurred in 24, 2 and 3% of PE cycles and 21, 12 and 1% of
      TOP. Non-hematologic toxicity was mild. The delivered dose intensity was 100% for
      PE and 93% for TOP. CONCLUSIONS: The sequential administration of TOP after PE is
      associated with manageable toxicity and may increase the number of CRs in
      patients with chemosensitive extensive stage SCLC. However, based on this data
      and the lack of survival benefit in a previous phase III study, the sequential
      regimen should not be used outside of a clinical trial.

PMID- 12499098
TI  - Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a
      novel sequence as first-line treatment of patients with small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy and tolerability of paclitaxel, carboplatin and
      etoposide when administered in combination to previously-untreated small-cell
      lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients (n=95) with limited
      stage disease (LSD; n=45) or extensive-stage disease (ESD; n=50) from 14 Spanish
      hospitals were entered into the study. Etoposide was administered 80 mg/m(2)/day
      intravenous (i.v.) on days 1, 2 and 3, paclitaxel 175 mg/m(2) i.v. on day 3 and
      carboplatin area-under-the-concentration-time-curve=6; i.v. on day 3, of a 3-week
      cycle, and repeated for up to 6 cycles. RESULTS: The overall response (OR) rate
      was 74% (n=70; 32 complete, 38 partial). Although the OR in LSD and ESD patients
      was similar (73 vs 74%, respectively), the percentage complete response was
      significantly higher among the former (49 vs 20%). The main toxicities were grade
      3-4 neutropenia and febrile neutropenia (62 and 18%, respectively) and there were
      3 toxic deaths. Other toxicities were rare or easily manageable. Disease-free
      survival and overall survival rates at 1 year were 53 and 70% in LSD and 18 and
      39% in ESD patients, respectively. CONCLUSION: The results indicate that the
      combination of paclitaxel, etoposide and carboplatin has an anti-tumour activity
      in SCLC that is comparable to other combination regimens, and is well tolerated.

PMID- 12499099
TI  - Weekly low-dose docetaxel in advanced non-small cell lung cancer previously
      treated with two chemotherapy regimens.
AB  - BACKGROUND: The role of salvage chemotherapy in advanced non-small cell lung
      cancer (NSCLC) is still controversial, but the recent development of a number of
      active antineoplastic agents has created new possibilities for disease
      management. The aim of this study was to evaluate the activity and safety of
      weekly docetaxel treatment in patients with advanced NSCLC previously treated
      with two chemotherapy regimens. PATIENTS AND METHODS: The study involved 26
      patients with histologically documented stage IIIB, IV or recurrent metastatic
      NSCLC previously treated with two non-taxane based-chemotherapy regimens. They
      all received docetaxel 25 mg/m(2)/week administered as a 1-h infusion in an
      outpatient setting with corticosteroid premedication. RESULTS: Fourteen of the 26
      patients (54%) had distant metastases and 12 (46%) chest-localised disease. Six
      patients (23%; confidence interval: 9.8-44.1%) showed a partial response, 8 (31%)
      stable disease, and 12 (46%) progressive disease. The median time to progression
      was 4 months (range 2-8), and the median survival was 7+ months (range 3-13+).
      There were no statistically significant differences between the global quality of
      life scores recorded at baseline and those recorded after subsequent cycles. The
      treatment was very well tolerated. CONCLUSION: The results of this study suggest
      that weekly low-dose docetaxel is effective, well tolerated and maintains a
      relatively good quality of life in patients with advanced NSCLC previously
      exposed to two chemotherapy regimens.

PMID- 12499100
TI  - Phase I study of the combination of gemcitabine and nedaplatin for treatment of
      previously untreated advanced non-small cell lung cancer.
AB  - This trial was conducted to determine the maximum-tolerated dose (MTD), principal
      toxicity, and recommend dose for phase II study of the combination of gemcitabine
      and nedaplatin in patients with advanced non-small cell lung cancer (NSCLC).
      Patients with previously untreated NSCLC were eligible if they had a performance
      status of 0-2, were 75 years or younger, and had adequate organ function. The
      doses of gemcitabine (days 1, 8) and nedaplatin (day 1) studied were 800/60,
      800/70, 800/80, 1000/80, and 1000/100 (mg/m(2)), repeated every 3 weeks. Toxicity
      could be assessed in all 21 patients enrolled, response could be assessed in 20
      patients. The patients were 12 men and 9 women with a mean age of 69 years
      (range, 47-75 years). Four patients had stage IIIB disease and 17 patients had
      stage IV disease. The most common histologic type was adenocarcinoma. The MTD was
      not reached even at the highest doses. The most frequent toxic effects were
      thrombocytopenia and neutropenia: grade 3 or 4 thrombocytopenia was observed in
      19% of patients, and grade 3 or 4 neutropenia in 24% of patients. Nonhematologic
      toxicities were mild. Grade 3 hepatic dysfunction occurred in 3 patients.
      Relatively few patients required dose modifications. The median dose-intensities
      were 91.5 and 93.1%, respectively, of the planned doses of gemcitabine and
      nedaplatin. The overall response rate was 35% (95% confidence interval, 15.4
      59.2%). All responses were seen above level 3. The MTD was not reached even at
      the highest combination doses. We recommend doses of 1000 mg/m(2) of gemcitabine
      and 100 mg/m(2) of nedaplatin for phase II study. This combination chemotherapy
      is active and well tolerated and warrants phase II study.

PMID- 12499101
TI  - Efficacy of modified regimen with attenuated doses of paclitaxel plus carboplatin
      combination chemotherapy in elderly and/or weak patients with advanced non-small
      cell lung cancer.
AB  - PURPOSE: We conducted this study to evaluate the activity and toxicity of a
      combination regimen of paclitaxel plus carboplatin in patients with advanced
      NSCLC aged 65 years or older and/or in those with an ECOG performance status (PS)
      2. MATERIALS AND METHODS: Chemotherapy-naive patients with unresectable
      pathologically-proven NSCLC and of either age >or=65 or ECOG PS 2 were eligible.
      Patients received modified regimen with attenuated doses of paclitaxel (135
      mg/m(2) i.v. for 3 h D1) and carboplatin (AUC=5, D1) every 3 weeks. RESULTS:
      Thirty-five patients were enrolled. Nineteen patients were aged 65 or older (54%)
      and 26 patients (74%) were ECOG PS 2. The objective response rate was 40% with 14
      partial responses. The median time to progression was 22 weeks. Grade 3
      leucopenia occurred in 1 cycle and one case of neutropenic fever. CONCLUSIONS:
      The modified regimen with attenuated doses of paclitaxel plus carboplatin
      combination chemotherapy was effective and well tolerated in patients with
      advanced NSCLC aged 65 years or older and/or in those with ECOG PS 2.

PMID- 12499102
TI  - Atypical lipomatous tumour (lipoma-like well-differentiated liposarcoma) arising
      in a pulmonary hamartoma and clinically presenting with pneumothorax.
AB  - We document an uncommon variant of pulmonary hamartoma (PH), discovered in the
      left upper lobe of a 60-year-old man after an episode of pneumothorax, a unique
      clinical presentation for such an occurrence. The tumour showed a prominent leaf
      like pattern and was mainly composed of mature fat with adipocytes of different
      size and scattered throughout lipoblasts and floret-like cells. A lobectomy was
      performed and more than 7 years after surgery the patient's course is still
      uneventful. This case represents an exceedingly rare example of an histologically
      malignant change in PH and bears a close clinicopathologic resemblance to
      atypical lipomatous tumours of soft tissues.

PMID- 12499103
TI  - Carboplatin and gemcitabine in stage IV non small cell lung cancer: beyond
      cisplatin in palliative chemotherapy.

PMID- 12499104
TI  - Mediastinal lymph-node dissection in the surgical treatment of non-small cell
      lung cancer. Is it still worthwhile?

PMID- 12499105
TI  - Similarity as transformation.
AB  - We propose that similarity is determined by the transformation distance between
      representations: entities which are perceived to be similar have representations
      which are readily transformed into one another, whereas transforming between
      dissimilar entities requires many transformations. We present three experiments
      that indicate that similarity is strongly influenced by transformation distance.
      These data present a challenge for featural or spatial accounts of similarity.
      Finally, we introduce a family of transformation-based accounts of similarity,
      called 'Representational Distortion', as a specific example of a transformational
      approach to similarity.

PMID- 12499106
TI  - The shape of holes.
AB  - The shape of holes can be recognized as accurately as the shape of objects
      (Palmer, S. E. (1999). Vision science: photons to phenomenology. Cambridge, MA:
      MIT Press), yet the area enclosed by a hole is a background region, and it can be
      demonstrated that background regions are not represented as having shape. What is
      therefore the shape of a hole, if any? To resolve this apparent paradox, we
      suggest that the shape of a hole is available indirectly from the shape of the
      surrounding object. We exploited the fact that observers are faster at judging
      the position of convex vertices than concave ones (Perception 30 (2001) 1295),
      and using a figural manipulation of figure/ground we found a reversal of the
      relative speeds when the same contours were presented as holes instead of
      objects. If contours were perceived as belonging to the hole rather than the
      surrounding object then there would have been no qualitative difference in
      responses to the object and hole stimuli. We conclude that the contour bounding a
      hole is automatically assigned to the surrounding object, and that a change in
      perception of a region from object to hole always drastically changes the encoded
      information. We discuss the many interesting aspects of holes as a subject of
      study in different disciplines and predict that much insight especially about
      shape will continue to come from holes.

PMID- 12499107
TI  - Abrupt onsets and gaze direction cues trigger independent reflexive attentional
      effects.
AB  - The present study investigated whether the direction of visual signals is
      influenced independently by two automatic visual orienting phenomena: orienting
      to a gazed-at location and inhibition of return (IOR) to the location of an
      abrupt onset. A schematic face served as both a nonpredictive gaze direction cue
      and an abrupt onset cue. Results indicated that target detection was facilitated
      at the gazed-at location, and that it was inhibited at the abrupt onset location.
      Importantly, these two different reflexive attention effects were triggered by
      the same event and exhibited overlapping time courses. Moreover, the IOR effect
      did not vary as a function of the facilitatory effect of gaze. These findings
      strongly suggest that reflexive attention to gaze direction and reflexive
      inhibition to an abrupt onset are independent processes, and that gaze direction
      does not produce IOR at the gazed-at location.

PMID- 12499108
TI  - Explaining modulation of reasoning by belief.
AB  - Although deductive reasoning is a closed system, one's beliefs about the world
      can influence validity judgements. To understand the associated functional
      neuroanatomy of this belief-bias we studied 14 volunteers using event-related
      fMRI, as they performed reasoning tasks under neutral, facilitatory and
      inhibitory belief conditions. We found evidence for the engagement of a left
      temporal lobe system during belief-based reasoning and a bilateral parietal lobe
      system during belief-neutral reasoning. Activation of right lateral prefrontal
      cortex was evident when subjects inhibited a prepotent response associated with
      belief-bias and correctly completed a logical task, a finding consistent with its
      putative role in cognitive monitoring. By contrast, when logical reasoning was
      overcome by belief-bias, there was engagement of ventral medial prefrontal
      cortex, a region implicated in affective processing. This latter involvement
      suggests that belief-bias effects in reasoning may be mediated through an
      influence of emotional processes on reasoning.

PMID- 12499109
TI  - The development of a word-learning strategy.
AB  - Two studies investigated young infants' use of the word-learning principle Mutual
      Exclusivity. In Experiment 1, a linear relationship between age and performance
      was discovered. Seventeen-month-old infants successfully used Mutual Exclusivity
      to map novel labels to novel objects in a preferential looking paradigm. That is,
      when presented a familiar and a novel object (e.g. car and phototube) and asked
      to "look at the dax", 17-month-olds increased looking to the novel object (i.e.
      phototube) above baseline preference. On these trials, 16-month-olds were at
      chance. And, 14-month-olds systematically increased looking to the familiar
      object (i.e. car) in response to hearing the novel label "dax". Experiment 2
      established that this increase in looking to the car was due solely to hearing
      the novel label "dax". Several possible interpretations of the surprising form of
      failure at 14 months are discussed.

PMID- 12499110
TI  - An empirical comparison of rhythm in language and music.
AB  - Musicologists and linguists have often suggested that the prosody of a culture's
      spoken language can influence the structure of its instrumental music. However,
      empirical data supporting this idea have been lacking. This has been partly due
      to the difficulty of developing and applying comparable quantitative measures to
      melody and rhythm in speech and music. This study uses a recently-developed
      measure for the study of speech rhythm to compare rhythmic patterns in English
      and French language and classical music. We find that English and French musical
      themes are significantly different in this measure of rhythm, which also
      differentiates the rhythm of spoken English and French. Thus, there is an
      empirical basis for the claim that spoken prosody leaves an imprint on the music
      of a culture.

PMID- 12499111
TI  - A perceptual interference account of acquisition difficulties for non-native
      phonemes.
AB  - This article presents an account of how early language experience can impede the
      acquisition of non-native phonemes during adulthood. The hypothesis is that early
      language experience alters relatively low-level perceptual processing, and that
      these changes interfere with the formation and adaptability of higher-level
      linguistic representations. Supporting data are presented from an experiment that
      tested the perception of English /r/ and /l/ by Japanese, German, and American
      adults. The underlying perceptual spaces for these phonemes were mapped using
      multidimensional scaling and compared to native-language categorization
      judgments. The results demonstrate that Japanese adults are most sensitive to an
      acoustic cue, F2, that is irrelevant to the English /r/-/l/ categorization.
      German adults, in contrast, have relatively high sensitivity to more critical
      acoustic cues. The results show how language-specific perceptual processing can
      alter the relative salience of within- and between-category acoustic variation,
      and thereby interfere with second language acquisition.

PMID- 12499112
TI  - 2,3-Dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid
      increase mercury- and cadmium-induced inhibition of delta-aminolevulinate
      dehydratase.
AB  - Compounds derived from Dimercaprol, such as meso-2,3-dimercaptosuccinic acid
      (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS), are becoming common
      agents for treating humans exposed to heavy metals. Heavy metals such as Pb(2+),
      Hg(2+) and Cd(2+) can inhibit delta-aminolevulinate dehydratase (delta-ALA-D)
      activity. Delta-ALA-D catalyzes the condensation of two delta-aminolevulinic acid
      (delta-ALA) molecules with the formation of porphobilinogen, a heme precursor.
      The effects of DMSA and DMPS alone or in combination with Cd(2+), Hg(2+), or
      Pb(2+) on hepatic delta-ALA-D were examined. DMPS and DMSA caused a dose
      dependent inhibition of hepatic delta-ALA-D. In the presence of Hg(2+) or Cd(2+)
      the inhibitory potency of DMPS increased. Similarly, the inhibitory effects of
      Hg(2+) and Cd(2+) were markedly increased in the presence of DMSA. In contrast,
      the inhibitory effect of DMPS was not changed by inclusion of Pb(2+). As observed
      with DMSA, Zn(2+) did not modified the inhibitory effect of DMPS. Data of the
      present report support the idea that the complexes formed (metals-DMSA or DMPS)
      were more inhibitory than the metal (Hg(2+) and Cd(2+)) or the chelating agent
      alone to the hepatic delta-ALA-D activity, in vitro. The mechanism of hepatic
      delta-ALA-D inhibition by Hg(2+)-DMPS/DMSA and Cd(2+)-DMPS/DMSA complexes involve
      the essential thiol groups of the enzyme.

PMID- 12499113
TI  - Species variations in cutaneous alcohol dehydrogenases and aldehyde
      dehydrogenases may impact on toxicological assessments of alcohols and aldehydes.
AB  - Alcohol dehydrogenase (ADH; EC. 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC
      1.2.1.3) play important roles in the metabolism of both endogenous and exogenous
      alcohols and aldehydes. The expression and localisation patterns of ADH (1-3) and
      ALDH (1-3) were investigated in the skin and liver of the mouse (BALB/c and
      CBA/ca), rat (F344) and guinea-pig (Dunkin-Hartley), using Western blot analysis
      and immunohistochemistry with class-specific antisera. ALDH2 expression and
      localisation was also determined in human skin, while ethanol oxidation,
      catalysed by ADH, was investigated in the mouse, guinea-pig and human skin
      cytosol. Western blot analysis revealed that ADH1, ADH3, ALDH1 and ALDH2 were
      expressed, constitutively, in the skin and liver of the mouse, rat and guinea
      pig. ADH2 was not detected in the skin of any rodent species/strain, but was
      present in all rodent livers. ALDH3 was expressed, constitutively, in the skin of
      both strains of mouse and rat, but was not detected in guinea-pig skin and was
      absent in all livers. Immunohistochemistry showed similar patterns of expression
      for ADH and ALDH in both strains of mouse, rat, guinea-pig and human skin
      sections, with localisation predominantly in the epidermis, sebaceous glands and
      hair follicles. ADH activity (apparent V(max), nmoles/mg protein/min) was higher
      in liver (6.02-16.67) compared to skin (0.32-1.21) and lower in human skin (0.32
      0.41) compared to mouse skin (1.07-1.21). The ADH inhibitor 4-methyl pyrazole (4
      MP) reduced ethanol oxidation in the skin and liver in a concentration dependent
      manner: activity was reduced to approximately 30-40% and approximately 2-10% of
      the control activity, in the skin and liver, respectively, using 1 mM 4-MP. The
      class-specific expression of ADH and ALDH enzymes, in the skin and liver and
      their variation between species, may have toxicological significance, with
      respect to the metabolism of endogenous and xenobiotic alcohols and aldehydes.

PMID- 12499114
TI  - Characterization of myoglobin toxicity in renal cortical slices from Fischer 344
      rats.
AB  - Rhabdomyolysis is associated with acute renal failure. The following study first
      characterized myoglobin in vitro toxicity using renal cortical slices isolated
      from male Fischer 344 rats. This model provided interaction between various cells
      within the nephron and provides myoglobin access predominantly through the
      basolateral membrane. Second, this study examined the effect of deferoxamine
      (DFX) and glutathione on myoglobin toxicity to determine the role of radicals and
      iron. Renal cortical slices were incubated for 30-120 min with 0, 4, 10 or 12
      mg/ml myoglobin. Myoglobin was pretreated with 4 mM ascorbic acid prior to
      addition to the slices to ensure that myoglobin was in its reduced state. In
      other experiments tissues were pretreated for 15 min with 0.1 mM of the iron
      chelator DFX or 30 min with 1 mM glutathione prior to co-incubation with
      myoglobin. Finally, slices were pretreated with 1 mM glutathione for 30 min,
      rinsed and incubated only with myoglobin. Early event changes occurred within a
      60 min exposure and included a decline in pyruvate-stimulated gluconeogenesis,
      increased lipid peroxidation levels and decreased glutathione levels. Loss of ATP
      levels and increased lactate dehydrogenase (LDH) release required a 120 min
      exposure to myoglobin. DFX reduced myoglobin induced effects on LDH leakage but
      had no effect on gluconeogenesis suggesting that myoglobin toxicity had an iron
      dependent (LDH) and independent (gluconeogenesis) pathway. Pretreatment with
      glutathione provided complete protection and was mediated by intracellular
      events.

PMID- 12499115
TI  - Intestinal permeability of chlorpyrifos using the single-pass intestinal
      perfusion method in the rat.
AB  - The intestinal transport of chlorpyrifos (CPF), an organothiophosphate pesticide,
      was investigated using the single-pass intestinal perfusion (SPIP) technique in
      male, Sprague-Dawley rats. SPIP was performed in each isolated region of the
      small intestine (i.e. duodenum, jejunum and ileum) with three concentrations of
      CPF (0.1, 2.0 and 10 microM) at a flow rate of 0.25 ml/min. Preliminary binding
      and stability studies were conducted to ensure that the loss of CPF in the SPIP
      study can be attributed to intestinal absorption. The effective permeability
      (P(eff)) of CPF was determined for each segment and concentration. CPF exhibits a
      high intestinal permeability over the length of the small intestine indicative of
      compounds that are well absorbed. Decreases in permeability values at the highest
      CPF concentration studied in the duodenum and ileum suggest a saturable transport
      process. Based on these results, passive, transcellular diffusion dominates the
      intestinal transport mechanism of CPF, with a saturable transport process evident
      in the duodenum and ileum. The P(eff) of CPF is in the range of drugs with high
      intestinal permeability and high fraction of dose absorbed indicating that CPF
      readily crosses the intestine. The dependence of CPF's P(eff) on concentration in
      the duodenum and ileum suggests that CPF is transported by a combination of
      mechanisms across the intestine. Using established relationships, the human
      fraction dose absorbed for CPF was estimated to be >99%. The permeability values
      obtained from this study may be useful in models of exposure assessment.

PMID- 12499116
TI  - Comparison of the toxicokinetics between perfluorocarboxylic acids with different
      carbon chain length.
AB  - Toxicokinetics was compared between perfluoroheptanoic acid (PFHA),
      perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and
      perfluorodecanoic acid (PFDA) in male and female rats. Half lives (t(1/2)) in
      male and female rats were calculated to be 0.10 and 0.05 days, respectively, for
      PFHA, 5.63 and 0.08 days for PFOA, 29.5 and 2.44 days for PFNA and 39.9 and 58.6
      days for PFDA. Total clearance (CL(tot)) of PFHA was higher than those of other
      perfluorocarboxylic acids (PFCAs) in both male and female rats. By contrast,
      CL(tot) of PFDA was extremely low in both sexes. PFCAs having shorter carbon
      chain length showed higher CL(tot). There was a significant sex-related
      difference in CL(tot) of PFOA and PFNA. Distribution volumes in steady state
      (V(ss)) were not much different between PFCAs and between sexes. To estimate the
      role of urinary excretion in plasma clearance of PFCA, renal clearance (CL(R))
      was determined for PFCAs. CL(R) of PFCAs were in the order PFHA>PFOA>PFNA
      approximately equal PFDA and PFHA approximately equal PFOA>PDNA>PFDA in male and
      female rats, respectively. There was a close relationship between CL(tot) and
      CL(R) (r(2)=0.981). Plasma protein binding, estimated in vitro, was over 98% for
      all PFCAs tested. The results indicate that CL(R) is responsible for the
      difference in CL(tot) between PFCAs having different carbon chain length and
      between sexes.

PMID- 12499117
TI  - Protection against ultraviolet B-induced oxidative DNA damage in rabbit corneal
      derived cells (SIRC) by 4-coumaric acid.
AB  - The exposure of cells to ultraviolet B radiation (UV-B) can induce the production
      of reactive oxygen species (ROS) which damage cellular components. Free radical
      scavengers and antioxidants can interfere with the production of ROS. We measured
      8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, a marker of oxidative DNA damage in
      rabbit corneal-derived cells (SIRC) exposed to UV-B in the presence of 4-coumaric
      acid, a natural polyphenol. The levels of 8-OHdG were increased significantly
      (P<0.01) following irradiation (from 12+/-1.2x10(-6) to 29+/-6.2x10(-6) dG,
      means+/-SE). When 10 microM 4-coumaric acid was added to the medium, 8-OHdG
      levels were similar to those of unexposed cells (16.8+/-0.8x10(-6) dG). UV-B
      irradiation decreased superoxide dismutase (SOD) activity in SIRC cells from
      0.29+/-0.6 to 0.15+/-0.04 mU/mg (means+/-SE). The presence of 10 microM 4
      coumaric acid prevented the decrease in SOD activity (0.20+/-0.05 mU/mg, P<0.05).
      On the contrary, SIRC cells exposed to UV-B had higher levels of xanthine oxidase
      (XO) activity compared with control ones (0.40+/-0.07 and 0.24+/-0.08 mU/mg,
      means+/-SE, respectively). In the presence of 10 microM 4-coumaric acid, the
      increase in XO activity was prevented (0.16+/-0.03 mU/mg; mean+/-SE). In
      conclusion, UV-B-induced oxidative DNA damage in SIRC cells is inhibited by 4
      coumaric acid, which, probably through its free radical scavenging activity,
      stabilizes SOD activity and blocks the increase of XO activity following UV-B
      irradiation. Thus, the topical use of 4-coumaric acid may prevent free radical
      damage in the cornea.

PMID- 12499118
TI  - The effect of acetylcholinesterase-inhibition on depolarization-induced GABA
      release from rat striatal slices.
AB  - The severity of poisoning after intoxication with the acetylcholinesterase (AChE)
      inhibitor soman has been shown to be positively correlated with GABA release in
      rat striatum. Since most of the neurons in striatum and striatal projection
      regions use GABA as transmitter, it is still unclear, whether an increase of
      extracellular GABA in this region results from enhanced activation of these
      projections or is due to the local effect of AChE inhibition. In this study, the
      modulation of depolarization-induced increase in GABA concentration by soman was
      determined in the superfusate of rat striatal slices. Soman and neostigmine
      increased GABA concentration in the superfusate dose dependently. This increase
      was exerted through M-cholinoceptors as it could be blocked by atropine and
      enhanced by application of the muscarinic agonists pilocarpine or oxotremorine.
      These results clearly indicate that AChE inhibition by soman in rat striatum can
      directly lead to enhanced release of GABA through M-cholinoceptors.

PMID- 12499119
TI  - Mechanisms regulating the cadmium-mediated suppression of Sp1 transcription
      factor activity in alveolar epithelial cells.
AB  - This study demonstrates that in vitro exposure of adult rat alveolar epithelial
      cells to CdCl(2) decreases DNA binding activity of specificity protein 1 (Sp1), a
      zinc-finger transcription factor known to play a key role in eukaryotic gene
      expression, maintenance of homeostasis, cell cycle control, terminal
      differentiation, and apoptosis. Suppression of Sp1 function, as assessed by
      electrophoretic mobility shift assays (EMSAs), is dependent upon cadmium (Cd)
      dose and duration of exposure. A 45% decrease of Sp1 activity occurs as early as
      30 min after Cd addition. By 2 h, Sp1 activity is reduced even further with no
      loss of cell viability, suggesting that Sp1 inactivation precedes cell death. If
      Cd is removed from cultures during these early periods of exposure, inhibition of
      Sp1 binding activity is reversed. Sp1 inactivation does not appear to be a
      generalized, non-selective response to Cd as other transcription factors are up
      regulated under the same conditions. Phosphorylation is involved in Sp1 down
      regulation, as evidenced by the finding that alkaline phosphatase treatment of
      nuclear extracts from cells exposed to Cd for 2 h helps restore Sp1 binding
      activity. A broad spectrum Protein Kinase C (PKC) inhibitor, GF109203X,
      substantially reduces the Cd-mediated effect on Sp1 suggesting that a member of
      the PKC family is required for Sp1 phosphorylation. More prolonged Cd exposure
      promotes Sp1 degradation with the appearance of cleavage products (40 and 50
      kDa), as detected by Western blotting. Changes in the integrity of the Sp1
      protein are accompanied by a corresponding decline in cell survival. Cd-induced
      cell death is substantially attenuated if cells are pretreated with antagonists
      of PKC activity which implies that a PKC isoform is also a participant in this
      process.

PMID- 12499120
TI  - Profile of nonprotein thiols, lipid peroxidation and delta-aminolevulinate
      dehydratase activity in mouse kidney and liver in response to acute exposure to
      mercuric chloride and sodium selenite.
AB  - The effects of mercury (Hg(2+)) and selenite (Se(4+)) on delta-aminolevulinic
      acid dehydratase (delta-ALA-D) activity, 2-thiobarbituric acid reactive
      substances (TBARS) and nonprotein sulfhydryl content (NPSH) in mouse kidney and
      liver were investigated. Male mice were given a single i.p. injection of Hg(2+)
      and/or Se(4+) (25 micromol/kg) and were killed at 6, 12, 24 and 48 h after
      treatment. Hg(2+) inhibited renal delta-ALA-D at 6 and 12 h after treatment.
      Se(4+) abolished the inhibitory effect of mercury on renal delta-ALA-D at 12 h
      after treatment. Renal and hepatic NPSH content decreased after Hg(2+) exposure
      and selenite inhibited, at least in part, the Hg-induced oxidation of renal and
      hepatic NPSH. Se(4+) and Hg(2+), when injected alone, did not alter hepatic or
      renal TBARS levels; however, simultaneous exposure to these compounds increased
      hepatic and renal TBARS levels at 12 and 48 h after treatment, respectively.
      Present results suggest that selenium abolishes the interaction of Hg(2+) with
      sulfhydryl groups of protein and nonprotein sources.

PMID- 12499121
TI  - Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat
      lung and alveolar epithelial cells.
AB  - The current study tested the hypothesis that the pulmonary carcinogenic potential
      of cadmium (Cd) is related to its ability to inhibit the expression (mRNA and
      protein) and activity of 8-oxoguanine-DNA glycosylase (OGG1), a base excision
      repair (BER) enzyme that functions to preferentially excise pre-mutagenic 7,8
      dihydro-8-oxoguanine (8-oxoG) from DNA. We demonstrate that a single Cd aerosol
      exposure of adult male Lewis rats causes time- and dose-dependent down-regulation
      in the pulmonary levels of rOGG1 mRNA and OGG1 protein, quantified by real-time
      reverse transcriptase-polymerase chain reaction (RT-PCR) assays and western
      analyses, respectively. Immunohistochemical studies confirmed that Cd inhalation
      reduces the relative amount of OGG1 in lungs of exposed animals without altering
      its over-all distribution within the lung, which appears to be more prominent
      within the alveolar epithelium. In agreement with our in vivo studies, we show
      that OGG1 expression is also attenuated in alveolar epithelial cell cultures
      exposed to CdCl(2) either acutely or by repeated passaging in Cd-containing
      medium. The effects caused by Cd were observed in cells that show no loss in
      viability, as assessed by colony forming ability, the MTT assay, and propidium
      iodide membrane permeability studies. Nuclear extracts prepared from Cd-treated
      cells also exhibit a reduction in the ability to nick a synthetic oligonucleotide
      containing 8-oxoG. We conclude from these studies that Cd causes suppression of
      OGG1 in the lung and that this mechanism may, in part, play a role in the Cd
      carcinogenic process.

PMID- 12499122
TI  - A study on CYP1A inhibitory action of E-2-(4'-methoxybenzylidene)-1-benzosuberone
      and some related chalcones and cyclic chalcone analogues.
AB  - In vivo investigation of E-2-(4'-methoxybenzylidene)-1-benzosuberone (4a) on the
      7,12-dimethylbenz[a]anthracene (DMBA)-induced onco/tumor suppressor gene
      expressions suggested that inhibition of metabolic activation of DMBA might play
      a role in the observed activity of the compound. In order to explore this
      possible biological action we have investigated whether 4a and some of its
      structurally related analogues had inhibitory effects on the CYP1A enzymes.
      During our study 7-ethoxyresorufin O-dealkylation activity of CYP1A isoenzymes
      was measured in liver microsomes prepared from 3-methylcholanthrene treated male
      rats. Inhibition constants (K(i) values) were determined by using different
      concentrations of 7-ethoxyresorufin and the investigated chalcones (1), E-2
      benzylidene-1-indanones (2), -tetralones (3) and -benzosuberones (4). Each
      compound was found to be a strong competitive inhibitor of the CYP1A enzymes.
      Their inhibitory activity was comparable with or even higher than that of 7,8
      benzoflavone, the known strong CYP1A inhibitor used as reference substance. By
      proper selection of the substituents on the benzylidene moiety we investigated
      how the inhibitory activity (K(i) value) of 1-4 varied as a function of the ring
      size (n=0, 5, 6, 7) carbon atoms, and the nature as well as the position of the
      substituents. To test applicability of the previously set structural requirements
      for binding of xenobiotics to the CYP1A enzymes we compared some topological,
      physico-chemical and quantum mechanical parameters of 1-4 with 7-ethoxyresorufin
      and 7,8-benzoflavone, the investigated CYP1A substrate and inhibitor,
      respectively.

PMID- 12499123
TI  - Effects of lipopolysaccharide-stimulated inflammation and pyrazole-mediated
      hepatocellular injury on mouse hepatic Cyp2a5 expression.
AB  - Murine hepatic cytochrome P450 2a5 (Cyp2a5) is induced during hepatotoxicity and
      hepatitis, however, the specific regulatory mechanisms have not been determined.
      We compared the influence of acute inflammation elicited in vivo by bacterial
      endotoxin lipopolysaccharide (LPS) and liver injury caused by the hepatotoxin
      pyrazole on hepatic Cyp2a5 expression in mice. Pyrazole treatment resulted in
      statistically significant increases in levels of Cyp2a5 mRNA, protein and
      catalytic activity by 540, 273 and 711%, respectively (P<0.05). In LPS-treated
      livers Cyp2a5 expression was significantly reduced compared to controls at the
      mRNA (46%) protein (35%), and activity (23%) levels (P<0.05). Treatment of mice
      with recombinant murine interleukin-1 beta and interleukin-6 had no significant
      effect on Cyp2a5 mRNA and protein levels. Liver injury, as assessed by serum
      alanine aminotransferase, was greater with pyrazole than with LPS treatment (609
      vs 354% of control levels respectively). ER stress, determined by hepatic glucose
      regulated protein 78 (grp78) levels, was greater with pyrazole (185% of controls)
      than with LPS (128% of controls). In pyrazole-treated liver, overexpression of
      immunoreactive grp78 protein revealed that ER stress was localized to pericentral
      hepatocytes in which Cyp2a5 was induced. Evidence of glycogen loss and membrane
      damage in these cells was suggestive of oxidative damage. Moreover, vitamin E
      attenuated Cyp2a5 induction by pyrazole in vivo. These results suggest that
      induction of Cyp2a5 that has been observed in mouse models of hepatitis and
      hepatoxicity may be related to oxidative injury to the endoplasmic reticulum of
      pericentral hepatocytes rather than exposure to pro-inflammatory cytokines.

PMID- 12499124
TI  - Effects of monocrotaline pyrrole and thrombin on pulmonary endothelial cell
      junction and matrix adhesion proteins.
AB  - Previous work in our laboratory has shown that monocrotaline pyrrole (MCTP)
      interacts with actin and potentiates thrombin-mediated endothelial barrier
      permeability through increasing the overall surface area of intercellular gaps.
      To better characterize endothelial barrier leak in this model, we examined the
      effects of MCTP and thrombin on the localization and structure of three adhesion
      associated proteins that directly or indirectly interact with actin in regulating
      barrier function: cell-cell occludens junction molecule (ZO-1), the cell-cell
      adherens junction linker, ss-catenin, and the cell-matrix intermediary signaling
      protein, focal adhesion kinase (FAK). Immunohistochemistry demonstrated that
      thrombin treatment resulted in radial reorganization of focal adhesions and
      broader distribution of adherens and occludins junctions at the cell border
      suggestive of membrane stretching in contracture. MCTP pretreatment resulted in
      fewer and more disorganized focal adhesions and marked thinning of occludins and
      adherens junctions. MCTP pretreatment also interfered with thrombin stimulated
      junctional reorganization. Western blot analysis showed thrombin stimulated
      catalysis of ZO-1 and FAK while MCTP pretreatment resulted in FAK fragmentation
      similar to previous reports for apoptosis. We conclude that both MCTP and
      thrombin alter critical endothelial cell adhesion molecules and this may be an
      underlying mechanism for the potentiating effect MCTP has on thrombin induced
      vascular permeability in vitro.

PMID- 12499125
TI  - Grief takes no holiday. For people who have lost loved ones, the holidays may
      elicit dread and apprehension. Here are some ideas that may help, now and year
      round.

PMID- 12499126
TI  - Banishing urinary tract infections. Prompt treatment reduces the risk of
      complications. And some simple lifestyle strategies can help prevent a
      recurrence.

PMID- 12499128
TI  - Mammograms: to screen or not to screen?

PMID- 12499127
TI  - Medications for postmenopausal osteoporosis prevention.

PMID- 12499129
TI  - By the way, doctor. I'm 50 years old, and like everybody else my age, I was
      vaccinated against smallpox before first grade. Do I still have some immunity?

PMID- 12499130
TI  - By the way, doctor. I would like to start the resistance-training program you
      outlined in your August 2002 issue. I feel fine now, but I had a heart attack
      five years ago. Is it safe for me to do those exercises?

PMID- 12499131
TI  - Aspirin and its rivals. As your options increase, your choices get harder.

PMID- 12499132
TI  - Diet wars I: How do you measure up?

PMID- 12499133
TI  - PC-SPES: A cautionary tale.

PMID- 12499134
TI  - On call. September 11 was an emotional day for all of us, but September 12 was a
      confusing day for me. I read two newspapers that reported on research in the New
      England Journal of Medicine. The New York Times headline said: "Prostate cancer
      surgery found to cut death risk," but the Washington Post announced: "Studies
      find no advantage to prostate cancer surgery." Which was right?

PMID- 12499135
TI  - Questioning child care. A government-funded study has provoked controversy about
      the effects of day care on children.

PMID- 12499136
TI  - Vagus nerve stimulation.

PMID- 12499137
TI  - Reversing race consciousness.

PMID- 12499138
TI  - The price of deinstitutionalization.

PMID- 12499139
TI  - Food for good behavior?

PMID- 12499140
TI  - Help from foster care.

PMID- 12499141
TI  - Heroin for addiction treatment.

PMID- 12499142
TI  - All in the head.

PMID- 12499143
TI  - Drinking and dementia.

PMID- 12499144
TI  - Top 10 health stories of 2002.

PMID- 12499145
TI  - Rules to eat by.

PMID- 12499146
TI  - Sinus infection detection.

PMID- 12499148
TI  - Surgery: does more equal better?

PMID- 12499147
TI  - Quitting HRT. Now that hormone replacement therapy has faded from the headlines,
      it's time to consider the nuances.

PMID- 12499149
TI  - Is it a cold or flu?

PMID- 12499150
TI  - Calcium and cancer.

PMID- 12499151
TI  - By the way, doctor. I'm 86 and have been getting four cortisone shots a year for
      the past several years for the arthritis in my right knee. But my doctor seems to
      think the shots are a bad idea. Doesn't the pain relief outweigh any long-term
      harm, especially at my age?

PMID- 12499153
TI  - A shortcut in the heart. Patent foramen ovale causes no problems in most people.
      But it may explain some mysterious strokes.

PMID- 12499152
TI  - By the way, doctor. I take vitamin E pills, but I've heard they can cause
      bleeding. Is this anything to worry about?

PMID- 12499154
TI  - Carbohydrates and health: Not that simple...or that complex. Taking control of
      your blood sugar and insulin levels may pay off for your heart and overall
      health.

PMID- 12499155
TI  - Cholesterol testing at home is more bother than benefit. You can avoid a trip to
      the doctor by testing your cholesterol at home. But the results won't give you
      the information you need.

PMID- 12499156
TI  - A close look at coenzyme Q10 and policosanol. Do these supplements live up to
      their claims for improving heart health?

PMID- 12499157
TI  - Heartwarming news for heart failure.

PMID- 12499158
TI  - Pregnancy problems echo later in life.

PMID- 12499159
TI  - Ask the doctor. I'm a 51-year-old man with no risk factors for heart disease
      other than being male. My blood pressure and cholesterol levels are fine. I
      exercise, and my diet is pretty good. I've never smoked. Yet I recently underwent
      a triple bypass for sudden chest pain. What could have caused this blockage and
      can I prevent future problems?

PMID- 12499160
TI  - Ask the doctor. I just got a pacemaker for a slow heartbeat. The idea that I am
      going to need to have the pacemaker changed when the battery runs out bothers me.
      Can I do anything to make my battery last longer?

PMID- 12499161
TI  - Transcriptional profile of the Escherichia coli response to the antimicrobial
      insect peptide cecropin A.
AB  - Cationic antimicrobial peptides are believed to exert their primary activities on
      anionic bacterial cell membranes; however, this model does not adequately account
      for several important structure-activity relationships. These relationships are
      likely to be influenced by the bacterial response to peptide challenge. In order
      to characterize the genomic aspect of this response, transcription profiles were
      examined for Escherichia coli isolates treated with sublethal and lethal
      concentrations of the cationic antimicrobial peptide cecropin A. Transcript
      levels for 26 genes changed significantly following treatment with sublethal
      peptide concentrations, and half of the transcripts corresponded to protein
      products with unknown function. The pattern of response is distinct from that
      following treatment with lethal concentrations and is also distinct from the
      bacterial response to nutritional, thermal, osmotic, or oxidative stress. These
      results demonstrate that cecropin A induces a genomic response in E. coli apart
      from any lethal effects on the membrane and suggest that a complete understanding
      of its mechanism of action may require a detailed examination of this response.

PMID- 12499162
TI  - VanD-type vancomycin-resistant Enterococcus faecium 10/96A.
AB  - VanD type Enterococcus faecium 10/96A is constitutively resistant to vancomycin
      and to low levels of teicoplanin by nearly exclusive synthesis of peptidoglycan
      precursors terminating in D-alanyl-D-lactate (L. M. Dalla Costa, P. E. Reynolds,
      H. A. Souza, D. C. Souza, M. F. Palepou, and N. Woodford, Antimicrob. Agents
      Chemother. 44:3444-3446, 2000). A G(184)S mutation adjacent to the serine
      involved in the binding of D-Ala1 in the D-alanine:D-alanine ligase (Ddl) led to
      production of an impaired Ddl and accounts for the lack of D-alanyl-D-alanine
      containing peptidoglycan precursors. The sequence of the vanD gene cluster
      revealed eight open reading frames. The organization of this operon, assigned to
      a chromosomal location, was similar to those in other VanD type strains. The
      distal part encoded the VanH(D) dehydrogenase, the VanD ligase, and the VanX(D)
      dipeptidase, which were homologous to the corresponding proteins in VanD-type
      strains. Upstream from the structural genes for these proteins was the vanY(D)
      gene; a frameshift mutation in this gene resulted in premature termination of the
      encoded protein and accounted for the lack of penicillin-susceptible D,D
      carboxypeptidase activity. Analysis of the translated sequence downstream from
      the stop codon, but in a different reading frame because of the frameshift
      mutation, indicated homology with penicillin binding proteins (PBPs) with a high
      degree of identity with VanY(D) from VanD-type strains. The 5' end of the gene
      cluster contained the vanR(D)-vanS(D) genes for a putative two-component
      regulatory system. Insertion of ISEfa4 in the vanS(D) gene led to constitutive
      expression of vancomycin resistance. This new insertion belonged to the IS605
      family and was composed of two open reading frames encoding putative transposases
      of two unrelated insertion sequence elements, IS200 and IS1341.

PMID- 12499163
TI  - Integration of a transposon Tn1-encoded inhibitor-resistant beta-lactamase gene,
      bla(TEM-67) from Proteus mirabilis, into the Escherichia coli chromosome.
AB  - Proteus mirabilis NEL-1 was isolated from a urine sample of a patient
      hospitalized in a long-term care facility. Strain NEL-1 produced a beta-lactamase
      with a pI of 5.2 conferring resistance to amoxicillin and amoxicillin-clavulanic
      acid. Sequencing of a PCR amplicon by using TEM-specific primers revealed a novel
      bla(TEM) gene, bla(TEM-67). TEM-67 was an IRT-1-like TEM derivative related to
      TEM-65 (Lys39, Cys244) with an additional Leu21Ile amino acid substitution in the
      leader peptide. The biochemical properties of TEM-67 were equivalent to those
      described for TEM-65. Analysis of sequences surrounding bla(TEM-67) revealed that
      it was located on a transposon, Tn1, which itself was located on a 48-kb non-self
      transferable plasmid, pANG-1. Electroporation of plasmid pANG-1 into Escherichia
      coli DH10B resulted in the integration of bla(TEM-67) into the chromosome,
      whereas it remained episomal in the P. mirabilis CIP103181 reference strain.
      Further characterization of pANG-1 revealed the presence of two identical
      sequences on both sides of Tn1 that contained an IS26 insertion sequence followed
      by a novel colicin gene, colZ, which had 20% amino acid identity with other
      colicin genes. The characterization of this novel TEM derivative provides further
      evidence for the large diversity of plasmid-encoded beta-lactamases produced in
      P. mirabilis and for their spread to other enterobacterial species through
      transposable-element-mediated events.

PMID- 12499164
TI  - Contributions of MexAB-OprM and an EmrE homolog to intrinsic resistance of
      Pseudomonas aeruginosa to aminoglycosides and dyes.
AB  - Of the six putative small multidrug resistance (SMR) family proteins of
      Pseudomonas aeruginosa, a protein encoded by the PA4990 gene (emrE(Pae)) shows
      the highest identity to the well-characterized EmrE efflux transporter of
      Escherichia coli. Reverse transcription-PCR confirmed the expression of emrE(Pae)
      in the wild-type strain of P. aeruginosa. Using isogenic emrE(Pae), mexAB-oprM,
      and/or mexB deletion mutants, the contributions of the EmrE protein and the MexAB
      OprM efflux system to drug resistance in P. aeruginosa were assessed by a drug
      susceptibility test carried out in a low-ionic-strength medium, Difco nutrient
      broth. We found that EmrE(Pae) contributed to intrinsic resistance not only to
      ethidium bromide and acriflavine but also to aminoglycosides. In this low-ionic
      strength medium, MexAB-OprM was also shown to contribute to aminoglycoside
      resistance, presumably via active efflux. Aminoglycoside resistance caused by
      these two pumps could not be demonstrated in high-ionic-strength media, such as
      Luria broth or Mueller-Hinton broth. The EmrE-dependent efflux of ethidium
      bromide was confirmed by a continuous fluorescence assay.

PMID- 12499165
TI  - Fluconazole susceptibility of vaginal isolates obtained from women with
      complicated Candida vaginitis: clinical implications.
AB  - Despite considerable evidence of azole resistance in oral candidiasis due to
      Candida species, little is known about the azole susceptibilities of the genital
      tract isolates responsible for vaginitis. The fluconazole susceptibilities of
      vaginal isolates obtained during a multicenter study of 556 women with
      complicated Candida vaginitis were determined by evaluating two fluconazole
      treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were
      highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.6%) were
      resistant (MICs, >or=64 microg/ml). Following fluconazole therapy, one case of in
      vitro resistance developed during 6 weeks of monitoring. In accordance with the
      NCCLS definition, in vitro fluconazole resistance correlated poorly with the
      clinical response, although a trend of a higher mycological failure rate was
      found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 micro
      g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue,
      no significant differences in the clinical and mycological responses were
      observed when isolates (n = 250) for which MICs were <or=1 microg/ml were
      compared with isolates (n = 30) for which MICs were >1 microg/ml, although a
      trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7;
      95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon,
      symptomatic recurrence or mycological relapse almost invariably occurred with
      highly sensitive strains (MICs, <1.0 microg/ml). In vitro fluconazole resistance
      developed in 2 of 18 initially susceptible C. glabrata isolates following
      fluconazole exposure. Susceptibility testing for women with complicated Candida
      vaginitis appears to be unjustified.

PMID- 12499166
TI  - In vitro activities of ABT-773 and other antimicrobials against human
      mycoplasmas.
AB  - The in vitro susceptibilities of 103 Mycoplasma pneumoniae isolates, 14
      Mycoplasma hominis isolates, 12 Mycoplasma fermentans isolates, and 24 Ureaplasma
      species to ABT-773, an investigational ketolide, and seven other agents were
      determined. For M. pneumoniae, the ABT-773 MIC at which 90% of isolates are
      inhibited (MIC(90); <or=0.001 microg/ml) was comparable to those of azithromycin,
      clarithromycin, and erythromycin and at least 128-fold lower than those of
      levofloxacin, gatifloxacin, moxifloxacin, and doxycycline. For M. fermentans, the
      ABT-773 MIC(90) (<or=0.008 microg/ml) was 2- to 128-fold lower than those of all
      other agents tested. For M. hominis, the ABT-773 MIC(90) (0.031 microg/ml) was
      equivalent to that of moxifloxacin, 2-fold lower than those of gatifloxacin and
      clindamycin, and 16-fold lower than that of levofloxacin. ABT-773 was equally
      active against doxycycline-susceptible and doxycycline-resistant organisms. The
      ABT-773 MICs (0.016 microg/ml) for Ureaplasma species were the lowest of those of
      any drug tested. The MIC(90) was 4- to 64-fold lower than those of
      clarithromycin, azithromycin, and erythromycin and >or=16-fold lower than those
      of all three fluoroquinolones. Minimal bactericidal concentrations determined for
      a subgroup of organisms were <or=0.063 micro g/ml for M. pneumoniae and 0.25
      microg/ml for M. fermentans, but they were several dilutions higher for M.
      hominis and Ureaplasma spp. ABT-773 has great potential for further study for the
      treatment of infections due to mycoplasmas and ureaplasmas.

PMID- 12499167
TI  - In vivo antibacterial activity of RWJ-54428, a new cephalosporin with activity
      against gram-positive bacteria.
AB  - RWJ-54428 (MC-02,479) is a new cephalosporin with activity against resistant gram
      positive organisms, including methicillin-resistant Staphylococcus aureus,
      vancomycin-resistant enterococci, and penicillin-resistant Streptococcus
      pneumoniae. The in vivo efficacy of RWJ-54428 was evaluated against gram-positive
      bacteria in four mouse models of infection. RWJ-54428 was effective in vivo
      against methicillin-susceptible and -resistant S. aureus in a mouse model of
      sepsis, with 50% effective doses being similar to those of vancomycin. In a
      single-dose neutropenic mouse thigh model of infection, RWJ-54428 at 30 mg/kg of
      body weight showed activity similar to that of vancomycin at 30 mg/kg against a
      strain of methicillin-resistant S. aureus. RWJ-54428 also showed a prolonged in
      vivo postantibiotic effect in this model. In a mouse model of pneumonia due to a
      penicillin-susceptible strain of Streptococcus pneumoniae, RWJ-54428 displayed
      efficacy and potency superior to those of penicillin G and cefotaxime. In a mouse
      model of pyelonephritis due to Enterococcus faecalis, RWJ-54428 had bactericidal
      effects similar to those of vancomycin and ampicillin, but at two- to threefold
      lower total daily doses. These studies show that RWJ-54428 is active in
      experimental mouse models of infection against gram-positive organisms, including
      strains resistant to earlier cephalosporins and penicillin G.

PMID- 12499168
TI  - Fourteen-member macrolides promote the phosphatidylserine receptor-dependent
      phagocytosis of apoptotic neutrophils by alveolar macrophages.
AB  - An inflammation of the airway of patients with diffuse panbronchiolitis (DPB), is
      characterized by dense neutrophil infiltration. Resolution of the inflammation
      can be achieved by the removal of apoptotic neutrophils by human alveolar
      macrophages (AM) without liberating neutrophil proteases in the airway. To
      understand clinical efficacy for the treatment of DPB by 14- or 15-member
      macrolides, their effects on the phagocytosis of apoptotic neutrophils by AM were
      examined. Treatment of AM with erythromycin (ERY) or clarithromycin at clinically
      achievable levels significantly increased the levels of phagocytosis of apoptotic
      neutrophils. A serum factor was not essential for the enhancement by these 14
      member macrolides. Of the antibiotics tested, these effects were specific for the
      14-member macrolides and a 15-member macrolide, azithromycin, but not for the 16
      member macrolides, clindamycin or beta-lactam antibiotics. The enhanced
      phagocytosis of apoptotic neutrophils by ERY had no effect on the levels of
      interleukin-8 or tumor necrosis factor alpha production by lipopolysaccharide
      stimulated AM after phagocytosis of the apoptotic neutrophils. The increased
      phagocytosis of apoptotic neutrophils by ERY was also found to be
      phosphatidylserine receptor-dependent for AM. These data indicate a novel anti
      inflammatory action of 14-member and 15-member macrolides, and suggest that such
      antibiotics achieve clinical efficacy for patients with DPB, in part, through
      enhancing the nonphlogistic phagocytosis of apoptotic neutrophils by AM.

PMID- 12499169
TI  - Correlation of phenotypic zidovudine resistance with mutational patterns in the
      reverse transcriptase of human immunodeficiency virus type 1: interpretation of
      established mutations and characterization of new polymorphisms at codons 208,
      211, and 214.
AB  - Zidovudine resistance (ZDV-R) is associated with classic genotypic changes at
      codons 41, 67, 70, 210, 215, and 219 of the human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT) gene as well as with the multinucleoside
      resistance (MNR) complexes (Q151M MNR complex; 6-bp insertion/A62V complex). In
      addition, enhanced resistance to ZDV in the context of the classic ZDV mutations
      plus the M184V mutation has been associated with additional mutations at
      positions 208, 211, 214, and 333. In this study we investigated phenotypic ZDV-R
      determined by a recombinant virus assay (Antivirogram; Virco) in 223 clinical
      samples in relation to the above genotypic changes. 150 out of 223 clinical
      samples had the M184V mutation. Phenotypic ZDV-R ranged from 0.3- to 5,338-fold.
      Sixteen samples (15 with high ZDV-R ranging from 90- to 3,571-fold) contained MNR
      associated patterns. Analysis of classic mutational patterns broadly demonstrated
      increasing ZDV-R with increasing number of ZDV mutations. A comparable
      correlation was obtained when ZDV-R was analyzed only relative to the T215Y/F
      mutation. Site-directed mutagenesis experiments investigating the influence of
      the additional mutations H208Y, R211K, and L214F on ZDV-R resulted in a 7.4- or
      21-fold increase in ZDV-R when the R211K/L214F or H208Y/R211K/L214F mutations,
      respectively, were added to a highly ZDV-R virus. In the clinical sample data set
      we analyzed, the combination of R211K/L214F appeared most frequently. The H208Y
      change was detected only in highly ZDV-R viruses, whereas the G333E/D change was
      distributed equally. All changes were independent of the M184V mutation. A 2.4-
      or 8-fold increase in ZDV-R was observed in the clinical samples with high ZDV-R
      containing the R211K/L214F or H208Y/R211K/L214F mutations, respectively. We have
      shown that the combination of the additional mutations H208Y, R211K, and L214F in
      HIV-1 RT may influence ZDV-R and should be considered when assessing ZDV-R.

PMID- 12499170
TI  - Mannopeptimycins, new cyclic glycopeptide antibiotics produced by Streptomyces
      hygroscopicus LL-AC98: antibacterial and mechanistic activities.
AB  - Mannopeptimycins alpha, beta, gamma, delta, and epsilon are new cyclic
      glycopeptide antibiotics produced by Streptomyces hygroscopicus LL-AC98.
      Mannopeptimycins gamma, delta, and epsilon, which have an isovaleryl substitution
      at various positions on the terminal mannose of the disaccharide moiety,
      demonstrated moderate to good antibacterial activities. Mannopeptimycin epsilon
      was the most active component against methicillin-resistant staphylococci and
      vancomycin-resistant enterococci (MICs, 2 to 4 micro g/ml for staphylococci and
      streptococci and 4 to 32 micro g/ml for enterococci), while mannopeptimycins
      gamma and delta were two- to fourfold less active. Mannopeptimycins alpha and
      beta, which lack the isovaleryl substitution and the disaccharide moiety,
      respectively, had poor antibacterial activities. The in vivo efficacies of the
      mannopeptimycins in Staphylococcus aureus mouse protection studies paralleled
      their in vitro activities. The median effective doses of mannopeptimycins gamma,
      delta, and epsilon were 3.8, 2.6, and 0.59 mg/kg of body weight, respectively.
      The mannopeptimycins were inactive against cell wall-deficient S. aureus and
      caused spheroplasting of Escherichia coli imp similar to that observed with
      penicillin G in an osmotically protective medium. Mannopeptimycin delta rapidly
      inhibited [(3)H]N-acetylglucosamine incorporation into peptidoglycan in Bacillus
      subtilis and had no effect on DNA, RNA, or protein biosynthesis. On the basis of
      the observations presented above, an effect on cell wall biosynthesis was
      suggested as the primary mode of action for mannopeptimycin delta. The
      mannopeptimycins were inactive against Candida albicans, did not initiate
      hemolysis of human erythrocytes, and did not promote potassium ion leakage from
      E. coli imp, suggesting a lack of membrane damage to prokaryotic or eukaryotic
      cells.

PMID- 12499171
TI  - Susceptibility of Candida dubliniensis to salivary histatin 3.
AB  - Candida dubliniensis is a recently described Candida species associated with oral
      candidiasis in human immunodeficiency virus (HIV)-infected patients and patients
      with AIDS. The majority of C. dubliniensis clinical isolates tested to date are
      susceptible to the commonly used antifungal drugs, including fluconazole,
      ketoconazole, itraconazole, and amphotericin B. However, the appearance of
      fluconazole-resistant C. dubliniensis strains in this patient group is
      increasing. Histatins are a family of basic histidine-rich proteins present in
      human saliva which have therapeutic potential in the treatment of oral
      candidiasis. The mechanism of action of histatin is distinct from that of
      commonly used azole and polyene drugs. Characterization of the antifungal
      activity of histatin has mainly been carried out using C. albicans but it is also
      effective in killing C. glabrata and C. krusei. Here we report that C.
      dubliniensis is also susceptible to killing by histatin 3. The concentration of
      histatin 3 giving 50% killing (the IC(50) value) ranged from 0.043 to 0.196 mg/ml
      among different strains of C. dubliniensis. The least-susceptible C. dubliniensis
      strain, P9224, was found to internalize histatin at a lower rate than the C.
      albicans reference strain CA132A. The dissociation constant (K(d)) for the least
      susceptible strain (C. dubliniensis 9224) was ninefold higher than that for the
      C. albicans reference strain. These results suggest that histatin 3 may have
      potential as an effective antifungal agent, particularly in the treatment of oral
      candidiasis in HIV-infected patients and patients with AIDS in which resistance
      to the commonly used antifungal drug fluconazole has emerged.

PMID- 12499172
TI  - Contribution of the 8-methoxy group to the activity of gatifloxacin against type
      II topoisomerases of Streptococcus pneumoniae.
AB  - The inhibitory activities (50% inhibitory concentrations [IC(50)s]) of
      gatifloxacin and other quinolones against both DNA gyrase and topoisomerase IV of
      the wild-type Streptococcus pneumoniae IID553 were determined. The IC(50)s of 10
      compounds ranged from 4.28 to 582 microg/ml against DNA gyrase and from 1.90 to
      35.2 microg/ml against topoisomerase IV. The inhibitory activity against DNA
      gyrase was more varied than that against topoisomerase IV among fluoroquinolones.
      The IC(50)s for DNA gyrase of the 8-methoxy quinolones gatifloxacin and AM-1147
      were approximately seven times lower than those of their 8-H counterparts AM-1121
      and ciprofloxacin, whereas the IC(50)s for topoisomerase IV were 1.5 times lower.
      Moreover, the IC(50) ratios (IC(50) for DNA gyrase/IC(50) for topoisomerase IV)
      of gatifloxacin, AM-1147, and moxifloxacin, which possess 8-methoxy groups, were
      almost the same. The 8-methoxy quinolones showed higher antibacterial activity
      and less mutant selectivity against IID553 than their 8-H counterparts. These
      results suggest that the 8-methoxy group enhances both target inhibition,
      especially for DNA gyrase, leading to potent antipneumococcal activity and dual
      inhibition against both DNA gyrase and topoisomerase IV in the bacterial cell.

PMID- 12499173
TI  - Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine.
AB  - The in vitro antifungal susceptibilities of six clinical Trichophyton rubrum
      isolates obtained sequentially from a single onychomycosis patient who failed
      oral terbinafine therapy (250 mg/day for 24 weeks) were determined by broth
      microdilution and macrodilution methodologies. Strain relatedness was examined by
      random amplified polymorphic DNA (RAPD) analyses. Data obtained from both broth
      micro- and macrodilution assays were in agreement and revealed that the six
      clinical isolates had greatly reduced susceptibilities to terbinafine. The MICs
      of terbinafine for these strains were >4 microg/ml, whereas they were <0.0002
      microg/ml for the susceptible reference strains. Consistent with these findings,
      the minimum fungicidal concentrations (MFCs) of terbinafine for all six strains
      were >128 microg/ml, whereas they were 0.0002 microg/ml for the reference strain.
      The MIC of terbinafine for the baseline strain (cultured at the initial screening
      visit and before therapy was started) was already 4,000-fold higher than normal,
      suggesting that this is a case of primary resistance to terbinafine. The results
      obtained by the broth macrodilution procedure revealed that the terbinafine MICs
      and MFCs for sequential isolates apparently increased during the course of
      therapy. RAPD analyses did not reveal any differences between the isolates. The
      terbinafine-resistant isolates exhibited normal susceptibilities to clinically
      available antimycotics including itraconazole, fluconazole, and griseofulvin.
      However, these isolates were fully cross resistant to several other known
      squalene epoxidase inhibitors, including naftifine, butenafine, tolnaftate, and
      tolciclate, suggesting a target-specific mechanism of resistance. This is the
      first confirmed report of terbinafine resistance in dermatophytes.

PMID- 12499174
TI  - pfcrt polymorphism and chloroquine resistance in Plasmodium falciparum strains
      isolated in Cambodia.
AB  - Plasmodium falciparum chloroquine resistance was first detected in Cambodia in
      the early sixties. Treatment with chloroquine was abandoned 20 years ago. In
      vitro chloroquine sensitivity monitoring indicates that all eastern Cambodian
      isolates were sensitive to chloroquine, whereas most isolates collected from
      western provinces displayed reduced susceptibility to chloroquine. This indicates
      that the rate of chloroquine resistance remains high and stable in this region in
      the absence of chloroquine pressure. Characterization of codons 72 to 78 and 218
      to 220 of pfcrt revealed six distinct haplotypes, four of which had never been
      described. The frequency of each haplotype depended on the geographical origin of
      the samples. The CVIETIF//ISS haplotype was detected in 92% of western Cambodian
      isolates and in 11% of isolates collected from the eastern province, where
      CVMNKIF//ISA and CVIDTIF//ISS predominate. The detection of an intermediate
      haplotype from a susceptible area with 76T/220A, suggests that acquisition of
      chloroquine resistance might be a stepwise process, during which accumulation of
      point mutations modulates the response to chloroquine. The association of the
      K76T mutation with chloroquine resistance was not clear. The mutation was
      detected in resistant and susceptible samples, suggesting that additional factors
      are involved in chloroquine resistance. By contrast, the pfcrt D/N75E mutation
      was strongly associated with the in vitro chloroquine resistance in Cambodian
      isolates. The N86 allelic form of pfmdr1 was detected in all isolates, consistent
      with a poor association with resistance to chloroquine. This indicates that in
      vitro resistance to chloroquine was associated with accumulation of point
      mutations in pfcrt.

PMID- 12499175
TI  - Regulation of membrane permeability by a two-component regulatory system in
      Pseudomonas aeruginosa.
AB  - Membrane impermeability is the major contributing factor to multidrug resistance
      in clinical isolates of Pseudomonas aeruginosa. By using laboratory strain PAK, a
      spontaneous P. aeruginosa mutant (mutant PAK1-3) whose membrane had reduced
      permeability and which displayed increased levels of resistance to various
      antibiotics, especially aminoglycosides, was isolated. By complementation of the
      mutant with a genomic clone library derived from wild-type strain PAK, a novel
      two-component regulatory system (PprA and PprB) was identified and was found to
      be able to increase the permeability of the bacterial membrane and render PAK1-3
      sensitive to antibiotics. Furthermore, specific phosphorylation of the response
      regulator (PprB) by histidine kinase (PprA) was observed in vitro, demonstrating
      that they are cognate two-component regulatory genes. Introduction of a plasmid
      expressing the pprB gene into randomly chosen clinical isolates (n = 17) resulted
      in increased sensitivity to aminoglycosides in the majority of isolates (n = 13)
      tested. This is the first demonstration that P. aeruginosa membrane permeability
      can be regulated, providing an important clue in the understanding of the
      mechanism of membrane impermeability-mediated multidrug resistance in P.
      aeruginosa.

PMID- 12499176
TI  - Antimicrobial susceptibilities of Campylobacter strains isolated from Finnish
      subjects infected domestically or from those infected abroad.
AB  - The in vitro susceptibilities of 678 Campylobacter jejuni and Campylobacter coli
      strains isolated from stool samples of the same number of Finnish subjects were
      studied. A total of 523 patients, representing inhabitants from throughout
      Finland, had not traveled abroad within the 2 weeks prior to becoming ill,
      whereas 155 persons had presumably acquired their infections abroad. The
      antimicrobial agents studied were erythromycin, ciprofloxacin, levofloxacin,
      trovafloxacin, and moxifloxacin. The MICs of these antimicrobial agents were
      determined by the agar dilution method. The growth of all domestic isolates was
      inhibited by erythromycin at concentrations of 4 microg/ml, and for these
      isolates the fluoroquinolone MICs at which 90% of isolates are inhibited
      (MIC(90)s) ranged from 0.06 to 0.5 microg/ml. For the foreign isolates, the
      erythromycin MIC(90) was still low (4 microg/ml), but their susceptibilities to
      fluoroquinolones were clearly reduced (MIC(90)s, 8 to 64 microg/ml). Of the four
      different fluoroquinolones studied, ciprofloxacin was the least active (MIC(90),
      64 micro g/ml).

PMID- 12499177
TI  - In vitro drug interaction modeling of combinations of azoles with terbinafine
      against clinical Scedosporium prolificans isolates.
AB  - The in vitro interaction between terbinafine and the azoles voriconazole,
      miconazole, and itraconazole against five clinical Scedosporium prolificans
      isolates after 48 and 72 h of incubation was tested by a microdilution
      checkerboard (eight-by-twelve) technique. The antifungal effects of the drugs
      alone and in combination on the fungal biomass as well as on the metabolic
      activity of fungi were measured using a spectrophotometric method and two
      colorimetric methods, based on the lowest drug concentrations showed 75 and 50%
      growth inhibition (MIC-1 and MIC-2, respectively). The nature and the intensity
      of the interactions were assessed using a nonparametric approach (fractional
      inhibitory concentration [FIC] index model) and a fully parametric response
      surface approach (Greco model) of the Loewe additivity (LA) no-interaction theory
      as well as a nonparametric (Prichard model) and a semiparametric response surface
      approaches of the Bliss independence (BI) no-interaction theory. Statistically
      significant synergy was found between each of the three azoles and terbinafine in
      all cases, although with different intensities. A 27- to 64-fold and 16- to 90
      fold reduction of the geometric mean of the azole and terbinafine MICs,
      respectively, was observed when they were combined, resulting in FIC indices of
      <1 to 0.02. Using the MIC-1 higher levels of synergy were obtained, which were
      more consistent between the two incubation periods than using the MIC-2. The
      strongest synergy among the azoles was found with miconazole using the BI-based
      models and with voriconazole using the LA-based models. The synergistic effects
      both on fungal growth and metabolic activity were more potent after 72 h of
      incubation. Fully parametric approaches in combination with the modified
      colorimetric method might prove useful for testing the in vitro interaction of
      antifungal drugs against filamentous fungi.

PMID- 12499178
TI  - Steady-state pharmacokinetics of amprenavir coadministered with ritonavir in
      human immunodeficiency virus type 1-infected patients.
AB  - The protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome
      P450 3A4, which boosts the activities of coadministered PIs, resulting in
      augmented plasma PI levels, simplification of the dosage regimen, and better
      efficacy against resistant viruses. The objectives of the present open-label,
      multiple-dose study were to determine the steady-state pharmacokinetics of
      amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at
      100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated
      with different antiretroviral combinations including or not including a
      nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients
      completed the study. The steady-state mean minimum plasma amprenavir
      concentration (C(min,ss)) was 1.92 microg/ml for patients who received amprenavir
      and ritonavir without an NNRTI and 1.36 microg/ml for patients who received
      amprenavir and ritonavir plus efavirenz. For patients who received amprenavir
      ritonavir without an NNRTI, the steady-state mean peak plasma amprenavir
      concentration (C(max,ss)) was 7.12 microg/ml, the area under the concentration
      time curve from 0 to 10 h (AUC(0-10)) was 32.06 microg. h/ml, and the area under
      the concentration-time curve over a dosing interval (12 h) at steady-state
      (AUC(ss)) was 35.74 microg. h/ml. Decreases in the mean values of C(min,ss)
      (29%), C(max,ss) (42%), AUC(0-10) (42%), and AUC(ss) (40%) for amprenavir
      occurred when efavirenz was coadministered with amprenavir-ritonavir. No
      unexpected side effects were observed. As expected, coadministration of
      amprenavir with ritonavir resulted in an amprenavir C(min,ss) markedly higher
      than those previously reported for the marketed dose of amprenavir. When
      amprenavir-ritonavir was coadministered with efavirenz, amprenavir-ritonavir
      maintained a mean amprenavir C(min,ss) above the mean 50% inhibitory
      concentration of amprenavir previously determined for both wild-type HIV-1
      isolates and HIV-1 strains isolated from PI-experienced patients. These data
      support the use of low-dose ritonavir to enhance the level of exposure to
      amprenavir and increase the efficacy of amprenavir.

PMID- 12499179
TI  - Ribavirin quantification in combination treatment of chronic hepatitis C.
AB  - Ribavirin in combination with alpha 2 interferon is the consensus treatment for
      chronic hepatitis C. However, recent preliminary pharmacological studies have
      suggested that the bioavailability of ribavirin displays great interindividual
      variability. In order to monitor serum ribavirin levels during combination
      treatment, we developed and validated a quantitative assay using an approach
      adaptable for routine hospital laboratories. The method involved solid-phase
      extraction on phenyl boronic acid cartridges followed by high-performance liquid
      chromatography with a C(18)-bonded silica column and a mobile phase containing 10
      mM ammonium phosphate buffer (with the pH adjusted to 2.5) and UV detection (207
      nm). The sensitivity, recovery, linearity of the calibration curve, intra- and
      interassay accuracies, precision, and stability at 4 degrees C were consistent
      with its use in the laboratory routine. In addition, other nucleoside analogues
      sometimes used with ribavirin in patients coinfected with hepatitis C virus (HCV)
      and human immunodeficiency virus did not interfere with the quantification of
      ribavirin levels. The ribavirin concentration was quantified in 24 serum samples
      from patients with chronic hepatitis C treated with a combination of ribavirin
      and alpha 2 interferon. The mean serum ribavirin concentration was 2.67 +/- 1.06
      micro g/ml (n = 24) at week 12 of treatment (W12) and 3.24 +/- 1.35 micro g/ml (n
      = 24) at week 24 of treatment (W24). In addition, ribavirin concentrations
      displayed high interindividual variabilities: the coefficients of variation of
      the serum ribavirin concentrations adjusted to the administered dose were 44 and
      48% at W12 and W24, respectively. Moreover, the ribavirin concentration was
      higher in patients with a sustained virological response (n = 11) than in
      patients with treatment failure (n = 13), with significant intergroup differences
      at W12 (P = 0.030) and W24 (P = 0.049). The present study describes a simple
      analytical method for the quantification of ribavirin in human serum that could
      be a useful tool for the monitoring of ribavirin concentrations in HCV-infected
      patients in order to improve the efficacy and safety of therapy with ribavirin
      plus interferon.

PMID- 12499180
TI  - Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and
      indinavir: Adult AIDS Clinical Trial Group Study 398.
AB  - The present population pharmacokinetic (PK) and pharmacodynamic (PD) study
      modeled the effects of covariates including drug adherence and the
      coadministration of protease inhibitors (PIs) on the pharmacokinetics of
      efavirenz (EFV) and the relationship between EFV exposure and virological failure
      in patients who failed initial PI treatment in Adult AIDS Clinical Trial Group
      (AACTG) study 398. We also report on the population PKs of the PIs nelfinavir
      (NFV) and indinavir (IDV). AACTG study 398 patients received EFV, amprenavir,
      adefovir dipivoxil, and abacavir and were randomized to take, in addition, one of
      the following: NFV, IDV, saquinavir (SQV), or placebo. The PK databases consisted
      of 531 EFV concentrations (139 patients), 219 NFV concentrations (75 patients),
      and 66 IDV concentrations (11 patients). Time to virological failure was
      ascertained for all patients in the PK databases. PK data were fit with a
      population PK model that assumed exclusive hepatic elimination (the well-stirred
      model). Notable findings with respect to EFV PK and PD are as follows. (i) The
      hepatic clearance of EFV is unaltered by NFV, IDV, or SQV coadministration. (ii)
      The hepatic clearance of EFV appears to be 28% higher in white non-Hispanics than
      in African Americans and Hispanics (P = 0.03). (iii) Higher adherence scores (as
      measured with the Medication Event Monitoring System) are associated with
      marginally increased levels of exposure to EFV. (iv) In patients with no prior
      experience with nonnucleoside reverse transcriptase inhibitors (NNRTIs), a given
      percent increase in the oral clearance (CL/F) of EFV is associated with a greater
      percent increase in the hazard of virological failure (P < 0.0003). Among NNRTI
      experienced patients, however, hazard is relatively uncorrelated with EFV CL/F.

PMID- 12499181
TI  - Modeling of transfer kinetics at the serum-cerebrospinal fluid barrier in rabbits
      with experimental meningitis: application to grepafloxacin.
AB  - The goals of the present study were to model the population kinetics of in vivo
      influx and efflux processes of grepafloxacin at the serum-cerebrospinal fluid
      (CSF) barrier and to propose a simulation-based approach to optimize the design
      of dose-finding trials in the meningitis rabbit model. Twenty-nine rabbits with
      pneumococcal meningitis receiving grepafloxacin at 15 mg/kg of body weight
      (intravenous administration at 0 h), 30 mg/kg (at 0 h), or 50 mg/kg twice (at 0
      and 4 h) were studied. A three-compartment population pharmacokinetic model was
      fit to the data with the program NONMEM (Nonlinear Mixed Effects Modeling).
      Passive diffusion clearance (CL(diff)) and active efflux clearance (CL(active))
      are transfer kinetic modeling parameters. Influx clearance is assumed to be equal
      to CL(diff), and efflux clearance is the sum of CL(diff), CL(active), and bulk
      flow clearance (CL(bulk)). The average influx clearance for the population was
      0.0055 ml/min (interindividual variability, 17%). Passive diffusion clearance was
      greater in rabbits receiving grepafloxacin at 15 mg/kg than in those treated with
      higher doses (0.0088 versus 0.0034 ml/min). Assuming a CL(bulk) of 0.01 ml/min,
      CL(active) was estimated to be 0.017 ml/min (11%), and clearance by total efflux
      was estimated to be 0.032 ml/min. The population kinetic model allows not only to
      quantify in vivo efflux and influx mechanisms at the serum-CSF barrier but also
      to analyze the effects of different dose regimens on transfer kinetic parameters
      in the rabbit meningitis model. The modeling-based approach also provides a tool
      for the simulation and prediction of various outcomes in which researchers might
      be interested, which is of great potential in designing dose-finding trials.

PMID- 12499182
TI  - Vancomycin acts synergistically with gentamicin against penicillin-resistant
      pneumococci by increasing the intracellular penetration of gentamicin.
AB  - Vancomycin and gentamicin act synergistically against penicillin-resistant
      pneumococci in vitro and in experimental rabbit meningitis. The aim of the
      present study was to investigate the underlying mechanism of this synergism. The
      intracellular concentration of gentamicin was measured by using the following
      experimental setting. Bacterial cultures were incubated with either gentamicin
      alone or gentamicin plus vancomycin for a short period (15 min). The gentamicin
      concentration was determined before and after grinding of the cultures by using
      the COBAS INTEGRA fluorescence polarization system (Roche). The grinding
      efficacies ranged between 44 and 54%, as determined by viable cell counts. In the
      combination regimen the intracellular concentration of gentamicin increased to
      186% compared to that achieved with gentamicin monotherapy. These data suggest
      that the synergy observed in vivo and in vitro is based on an increased
      intracellular penetration of the aminoglycoside, probably due to the effect of
      vancomycin on the permeability of the cell wall.

PMID- 12499183
TI  - Bacteremia due to Bacteroides fragilis group: distribution of species, beta
      lactamase production, and antimicrobial susceptibility patterns.
AB  - A retrospective analysis of susceptibility data on 542 blood isolates of the
      Bacteroides fragilis group tested from 1987 to 1999 by the same NCCLS-recommended
      broth microdilution method throughout is presented. Metronidazole, beta-lactam
      beta-lactamase inhibitor combinations, carbapenems, and trovafloxacin were the
      most active agents (susceptibility of >or=93%). Among the cephalosporin
      cephamycins, the order of activity was cefoxitin > ceftizoxime > cefotetan =
      cefotaxime = cefmetazole > ceftriaxone. All isolates were resistant to penicillin
      G, and 22% were resistant to clindamycin. The susceptibility rates to
      piperacillin-tazobactam, imipenem, and meropenem were affected least among
      isolates resistant to cefoxitin or clindamycin. Except for piperacillin
      tazobactam, imipenem, and meropenem, the B. fragilis species was more susceptible
      than were the non-B. fragilis species. These data underscore the importance of
      susceptibility testing of the B. fragilis group and can serve as a guide in the
      choice of empirical antimicrobial therapy.

PMID- 12499185
TI  - In vitro susceptibilities to and bactericidal activities of garenoxacin (BMS
      284756) and other antimicrobial agents against human mycoplasmas and ureaplasmas.
AB  - The in vitro susceptibilities to garenoxacin (BMS-284756), an investigational des
      fluoroquinolone, and eight other agents were determined for 63 Mycoplasma
      pneumoniae, 45 Mycoplasma hominis, 15 Mycoplasma fermentans, and 68 Ureaplasma
      sp. isolates. Garenoxacin was the most active quinolone, inhibiting all isolates
      at <or=1 microg/ml. The garenoxacin MIC at which 90% of isolates are inhibited
      (MIC(90)s; <or=0.008 microg/ml) was at least 4-fold less than those of
      moxifloxacin and clindamycin, 8-fold less than that of sparfloxacin, and 64-fold
      less than those of levofloxacin and ciprofloxacin for M. pneumoniae. For M.
      hominis, the garenoxacin MIC(90) (<or=0.008 microg/ml) was 4-fold less than those
      of clindamycin and moxifloxacin, 8-fold less than that of sparfloxacin, and 64
      fold less than those of levofloxacin and ciprofloxacin. All 15 M. fermentans
      isolates were inhibited by garenoxacin at concentrations <or=0.008 microg/ml,
      making it the most active drug tested against this organism. For Ureaplasma spp.,
      the garenoxacin MIC(90) (0.25 microg/ml) was equivalent to those of moxifloxacin
      and doxycycline, 4-fold less than those of levofloxacin and sparfloxacin, 8-fold
      less than that of azithromycin, and 32-fold less than that of ciprofloxacin.
      Garenoxacin and the other fluoroquinolones tested were demonstrated to have
      bactericidal activities against M. pneumoniae and M. hominis by measurement of
      minimal bactericidal activities and by time-kill studies. Further study of
      garenoxacin is required, as it has great potential for use in the treatment of
      infections due to mycoplasmas and ureaplasmas.

PMID- 12499184
TI  - Structure-activity relationships for inhibition of cysteine protease activity and
      development of Plasmodium falciparum by peptidyl vinyl sulfones.
AB  - The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 appear
      to be required for hemoglobin hydrolysis by intraerythrocytic malaria parasites.
      Previous studies showed that peptidyl vinyl sulfone inhibitors of falcipain-2
      blocked the development of P. falciparum in culture and exerted antimalarial
      effects in vivo. We now report the structure-activity relationships for
      inhibition of falcipain-2, falcipain-3, and parasite development by 39 new vinyl
      sulfone, vinyl sulfonate ester, and vinyl sulfonamide cysteine protease
      inhibitors. Levels of inhibition of falcipain-2 and falcipain-3 were generally
      similar, and many potent compounds were identified. Optimal antimalarial
      compounds, which inhibited P. falciparum development at low nanomolar
      concentrations, were phenyl vinyl sulfones, vinyl sulfonate esters, and vinyl
      sulfonamides with P(2) leucine moieties. Our results identify independent
      structural correlates of falcipain inhibition and antiparasitic activity and
      suggest that peptidyl vinyl sulfones have promise as antimalarial agents.

PMID- 12499186
TI  - In vitro activities of cethromycin (ABT-773), a new ketolide, against
      Streptococcus pneumoniae strains that are not susceptible to penicillin or
      macrolides.
AB  - Pneumococcal resistance to antimicrobials presents problems to physicians for
      empirical treatment of acute otitis media (AOM). Three hundred thirty-three
      isolates of Streptococcus pneumoniae selected for nonsusceptibility to penicillin
      (MIC >0.1 microg/ml) from the middle ear (n = 325) or mastoid (n = 8) of children
      seen between 1994 and 2000 at four children's hospitals in the United States were
      tested by broth microdilution for susceptibility to nine antibiotics. Using NCCLS
      2002 breakpoints, resistance to the following drugs was as indicated:
      amoxicillin, 1%; azithromycin, 71%; cefprozil, 71%; ceftriaxone, 2%; cefdinir,
      98%; erythromycin, 70%; levofloxacin, 0%; and trimethoprim-sulfamethoxazole, 93%.
      Of the penicillin- and erythromycin-nonsusceptible isolates, 97% were inhibited
      by cethromycin (ABT-773) and 83% were inhibited by telithromycin at a
      concentration of <or=0.125 microg/ml. Macrolide resistance among penicillin
      nonsusceptible pneumococci increased from 44 to 80% in the 6 years of the study
      from which the isolates were selected; however, the proportion of isolates with M
      or MLS(B) phenotypes remained constant over the time period (53 and 18%,
      respectively). Prior treatment with a macrolide or clindamycin alone or in
      combination with a beta-lactam resulted in 94 or 85% of isolates causing
      infections being macrolide and or clindamycin resistant. No prior individual
      macrolide (azithromycin, erythromycin, or clarithromycin) resulted in more
      macrolide resistance or in a more prevalent resistance phenotype. The ketolides
      appear to be active antimicrobials against penicillin- and macrolide-resistant
      pneumococci.

PMID- 12499187
TI  - Simple in vitro assay for determining the sensitivity of Plasmodium vivax
      isolates from fresh human blood to antimalarials in areas where P. vivax is
      endemic.
AB  - The aim of this study was to develop a simple, field-practical, and effective in
      vitro method for determining the sensitivity of fresh erythrocytic Plasmodium
      vivax isolates to a range of antimalarials. The method used is a modification of
      the standard World Health Organization (WHO) microtest for determination of P.
      falciparum drug sensitivity. The WHO method was modified by removing leukocytes
      and using a growth medium supplemented with AB(+) serum. We successfully carried
      out 34 in vitro drug assays on 39 P. vivax isolates collected from the Mae Sod
      malaria clinic, Tak Province, Thailand. The mean percentage of parasites maturing
      to schizonts (six or more merozoites) in control wells was 66.5% +/- 5.9%
      (standard deviation). This level of growth in the control wells enabled rapid
      microscopic determination (5 min per isolate per drug) of the MICs of
      chloroquine, dihydroartemisinin, WR238605 (tafenoquine), and sulfadoxine. P.
      vivax was relatively sensitive to chloroquine (MIC = 160 ng/ml, 50% inhibitory
      concentration [IC(50)] = 49.8 ng/ml) and dihydroartemisinin (MIC = 0.5 ng/ml,
      IC(50) = 0.47 ng/ml). The poor response of P. vivax to both tafenoquine (MIC =
      14,000 ng/ml, IC(50) = 9,739 ng/ml) and sulfadoxine (MIC = 500,000 ng/ml, IC(50)
      = 249,000 ng/ml) was due to the slow action of these drugs and the innate
      resistance of P. vivax to sulfadoxine. The in vitro assay developed in our study
      should be useful both for assessing the antimalarial sensitivity of P. vivax
      populations and for screening new antimalarials in the absence of long-term P.
      vivax cultures.

PMID- 12499188
TI  - In vitro activities of 7-substituted 9-chloro and 9-amino-2-methoxyacridines and
      their bis- and tetra-acridine complexes against Leishmania infantum.
AB  - 9-Chloro and 9-amino-2-methoxyacridines bearing different substituents in
      position 7, as well as their corresponding unsubstituted dimeric and tetrameric
      complexes, were investigated for in vitro antiproliferative properties against
      Leishmania infantum compared to toxicity towards human monocytes. The results
      clearly confirmed that several compounds of the 2-methoxyacridine series,
      together with their corresponding dimeric and tetrameric derivatives, had strong
      in vitro antiparasitic properties. Antileishmanial activity was shown to depend
      on the nature of both 7- and 9-substituted groups in monoacridines, while it
      varied according to the nature of the 9-substituted group and the length of the
      linker among bis- and tetra-acridines. The effects of acridine derivatives on DNA
      synthesis raised the hypothesis that DNA metabolism constituted their main target
      in Leishmania promastigotes; however, secondary effects on other biochemical
      pathways, including protein and lipid metabolism, were observed, suggesting that
      acridine compounds could be considered multitarget drugs.

PMID- 12499189
TI  - The proton channel is the minimal structure of ATP synthase necessary and
      sufficient for microcin h47 antibiotic action.
AB  - It had been previously determined that the presence of F(o)F(1) ATP synthase was
      required for microcin H47 antibiotic action. In this work, microcin-resistant atp
      mutants were genetically analyzed. Their mutations, originated by Tn5 insertion,
      in all cases were found to affect determinants for the F(o) portion of ATP
      synthase. To discern if microcin action required the presence of the entire
      complex or if the F(o) proton channel would suffice, recombinant plasmids
      carrying different segments of the atp operon were constructed and introduced
      into an atp deletion strain. The phenotypic analysis of the strains thus obtained
      clearly indicated that the presence of the F(o) proton channel was absolutely
      required for microcin H47 action, while the F(1) catalytic portion was found to
      be dispensable. Furthermore, when any of the three components of the proton
      channel was missing, total resistance to the antibiotic ensued. Complementation
      analysis between atp::Tn5 chromosomal mutations and recombinant atp plasmid
      constructions further supported the idea that the proton channel would be the
      minimal structure of the ATP synthase complex needed for microcin H47 antibiotic
      action.

PMID- 12499190
TI  - Exploring the structure and function of the mycobacterial KatG protein using
      trans-dominant mutants.
AB  - In order to probe the structure and function of the mycobacterial catalase
      peroxidase enzyme (KatG), we employed a genetic approach using dominant-negative
      analysis of katG merodiploids. Transformation of Mycobacterium bovis BCG with
      various katG point mutants (expressed from low-copy-number plasmids) resulted in
      reductions in peroxidase and catalase activities as measured in cell extracts.
      These reductions in enzymatic activity usually correlated with increased
      resistance to the antituberculosis drug isoniazid (INH). However, for the N138S
      trans-dominant mutant, the catalase-peroxidase activity was significantly
      decreased while the sensitivity to INH was retained. trans-dominance required
      katG expression from multicopy plasmids and could not be demonstrated with katG
      mutants integrated elsewhere on the wild-type M. bovis BCG chromosome. Reversal
      of the mutant phenotype through plasmid exchange suggested the catalase
      peroxidase deficiency occurred at the protein level and that INH resistance was
      not due to a second site mutation(s). Electrophoretic analysis of KatG proteins
      from the trans-dominant mutants showed a reduction in KatG dimers compared to WT
      and formation of heterodimers with reduced activity. The mutants responsible for
      these defects cluster around proposed active site residues: N138S, T275P, S315T,
      and D381G. In an attempt to identify mutants that might delimit the region(s) of
      KatG involved in subunit interactions, C-terminal truncations were constructed
      (with and without the D381G dominant-negative mutation). None of the C-terminal
      deletions were able to complement a DeltakatG strain, nor could they cause a
      dominant-negative effect on the WT. Taken together, these results suggest an
      intricate association between the amino- and carboxy-terminal regions of KatG and
      may be consistent with a domain-swapping mechanism for KatG dimer formation.

PMID- 12499191
TI  - Comparative molecular analysis of community- or hospital-acquired methicillin
      resistant Staphylococcus aureus.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a
      growing public health concern that has been associated with pediatric fatalities.
      It is hypothesized that the evolution of CA-MRSA is a recent event due to the
      acquisition of mec DNA by previously methicillin-susceptible strains that
      circulated in the community. This study investigated the genetic relatedness
      between CA-MRSA, hospital-associated MRSA (HA-MRSA), and nonmenstrual toxic shock
      syndrome (nmTSS) isolates. Thirty-one of 32 CA-MRSA isolates were highly related
      as determined by pulsed-field gel electrophoresis and spa typing yet were
      distinguishable from 32 HA-MRSA strains. The 31 related CA-MRSA isolates produced
      either staphylococcal enterotoxin B (n = 5) or C (n = 26), and none made TSS
      toxin 1. All CA-MRSA isolates tested contained a type IV staphylococcal cassette
      chromosome mec (SCCmec) element. In comparison, none of the HA-MRSA isolates (n =
      32) expressed the three superantigens. Antibiotic susceptibility patterns were
      different between the CA-MRSA and HA-MRSA isolates; CA-MRSA was typically
      resistant only to beta-lactam antibiotics. Six of twenty-one nmTSS isolates were
      indistinguishable or highly related to the CA-MRSA isolates. MnCop, an nmTSS
      isolate obtained in Alabama in 1986, was highly related to the CA-MRSA isolates
      except that it did not contain an SCCmec element. These data suggest that CA-MRSA
      strains may represent a new acquisition of SCCmec DNA in a previously susceptible
      genetic background that was capable of causing nmTSS. CA-MRSA poses a serious
      health risk not only because it is resistant to the antibiotics of choice for
      community-acquired staphylococcal infections but also because of its ability to
      cause nmTSS via superantigen production.

PMID- 12499192
TI  - A clonal lineage of VanA-type Enterococcus faecalis predominates in vancomycin
      resistant Enterococci isolated in New Zealand.
AB  - Avoparcin was used as a feed additive in New Zealand broiler production from 1977
      until June 2000. We report here on the effects of the usage and discontinuation
      of avoparcin on the prevalence of vancomycin-resistant enterococci (VRE) in
      broilers. Eighty-two VRE isolates were recovered from poultry fecal samples
      between 2000 and mid-2001. VRE isolates were only obtained from broiler farms
      that were using, or had previously used, avoparcin as a dietary supplement. Of
      these VRE isolates, 73 (89%) were VanA-type Enterococcus faecalis and nine (11%)
      were VanA-type Enterococcus faecium. All E. faecalis isolates were found to have
      an identical or closely related pulsed-field gel electrophoresis (PFGE) pattern
      of SmaI-digested DNA and were susceptible to both ampicillin and gentamicin. The
      PFGE patterns of the nine E. faecium isolates were heterogeneous. All VRE
      contained both the vanA and ermB genes, which, regardless of species or PFGE
      pattern, resided on the same plasmid. Eighty-seven percent of the VRE isolates
      also harbored the tet(M) gene, while for 63 and 100%, respectively, of these
      isolates, the avilamycin and bacitracin MICs were high (>or=256 microg/ml). Five
      of eight vancomycin-resistant E. faecalis isolates recovered from humans in New
      Zealand revealed a PFGE pattern identical or closely related to that of the E.
      faecalis poultry VRE isolates. Molecular characterization of Tn1546-like elements
      from the VRE showed that identical transposons were present in isolates from
      poultry and humans. Based on the findings presented here, a clonal lineage of
      VanA-type E. faecalis dominates in VRE isolated from poultry and humans in New
      Zealand.

PMID- 12499193
TI  - Garenoxacin (BMS-284756) and moxifloxacin in experimental meningitis caused by
      vancomycin-tolerant pneumococci.
AB  - The emergence of multidrug-resistant strains of Streptococcus pneumoniae drives
      the development and evaluation of new antipneumococcal agents, especially for the
      treatment of bacterial meningitis. The aims of the present study were to assess
      the antibacterial effectiveness of two new quinolones, garenoxacin (BMS; BMS
      284756) and moxifloxacin (MOX) in experimental meningitis caused by a vancomycin
      (VAN)-tolerant S. pneumoniae strain and to compare the results with those
      obtained by therapy with VAN and ceftriaxone (CRO) in combination. Meningitis was
      induced in young male New Zealand White rabbits by intracisternal inoculation of
      a VAN-tolerant pneumococcal strain (strain Tupelo) from a child with meningitis.
      Sixteen hours after inoculation, therapy was given by intravenous administration
      of BMS at 20 mg/kg of body weight, followed 5 h later by administration at a
      dosage of 10 mg/kg (n = 9 animals) or MOX as two doses of 20 mg/kg every 5 h (n =
      8 animals). For comparison, we studied the following groups: (i) animals treated
      with VAN (20 mg/kg every 5 h, three doses) and CRO (125 mg/kg, one dose) (n = 9),
      (ii) animals infected with a VAN-tolerant strain but not treated (n = 8), (iii)
      animals infected with a VAN-tolerant pneumococcus isolated from the nasopharynx
      of a carrier and treated with BMS (n = 8), and (iv) animals infected with a
      cephalosporin-resistant type 6B S. pneumoniae strain and treated with BMS (n =
      6). The MICs of penicillin, CRO, VAN, BMS, and MOX for the Tupelo strain were 2,
      1, 0.5, 0.06, and 0.03 micro g/ml, respectively. The rates of killing of strain
      Tupelo (the change in the log(10) number of CFU per milliliter per hour) in
      cerebrospinal fluid at 5 h were -0.70 +/- 0.35, -0.61 +/- 0.44, and -0.49 +/-
      0.36 for BMS, MOX, and VAN-CRO, respectively. Therapy with BMS and MOX was as
      effective as therapy with VAN-CRO against VAN-tolerant pneumococcal meningitis in
      rabbits.

PMID- 12499194
TI  - Activity and diffusion of tigecycline (GAR-936) in experimental enterococcal
      endocarditis.
AB  - The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in
      vitro and in experimental endocarditis due to the susceptible Enterococcus
      faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA
      type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were
      0.06 micro g/ml for the three strains. In vitro pharmacodynamic studies
      demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by
      increasing concentrations to more than 1 micro g/ml and a postantibiotic effect
      ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous
      injection of [(14)C]GAR-936 to five rabbits with enterococcal endocarditis
      sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower
      clearance of GAR-936 from aortic vegetations than from serum and a homogeneous
      diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936
      (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was
      bacteriostatic against both strains of E. faecalis. Against E. faecium HB217,
      bacterial counts in vegetations significantly decreased during therapy (P <
      0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once
      a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly
      above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR
      936-resistant mutants were selected in vivo with any regimen. We concluded that
      the combination of prolonged half-life, significant postantibiotic effect, and
      good and homogeneous diffusion into the vegetations may account for the in vivo
      activity of GAR-936 against enterococci susceptible or resistant to glycopeptides
      and tetracyclines, even when using a o.d. regimen in rabbits.

PMID- 12499195
TI  - Chemotherapy with benznidazole and itraconazole for mice infected with different
      Trypanosoma cruzi clonal genotypes.
AB  - The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set
      of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the
      chronic phase of experimental chagasic infection in BALB/c mice. Twenty
      laboratory-cloned stocks representative of the total phylogenetic diversity of T.
      cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T.
      cruzi II), were analyzed. Our results demonstrate important differences among
      stocks that could be pointed out as markers of biological behavior. Members of
      the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of
      the T. cruzi II group were partially resistant to both drugs, despite their
      susceptibilities to ITC during the chronic phase of infection. The resistance to
      BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas
      resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns
      of response to BZ observed for genotype 39 isolates had a major impact on the
      partial resistance pattern observed for members of the T. cruzi II group.
      Genotype 32 isolates showed a typical profile of susceptibility. The correlation
      between the response to treatment and phylogenetic classification of T. cruzi
      stocks was clearer for ITC than for BZ. In conclusion, the data presented show a
      correlation between phylogenetic divergence among T. cruzi stocks and their
      susceptibilities to chemotherapeutic agents in vivo. Our results warn of the
      necessity to take into account the lesser genetic subdivisions of T. cruzi stocks
      since the upper subdivisions (T. cruzi I and II) show a great deal of
      heterogeneity for in vivo drug susceptibility.

PMID- 12499196
TI  - Combination of drug level measurement and parasite genotyping data for improved
      assessment of amodiaquine and sulfadoxine-pyrimethamine efficacies in treating
      Plasmodium falciparum malaria in Gabonese children.
AB  - Many African countries currently use a sulfadoxine-pyrimethamine combination (SP)
      or amodiaquine (AQ) to treat uncomplicated Plasmodium falciparum malaria. Both
      drugs represent the last inexpensive alternatives to chloroquine. However,
      resistant P. falciparum populations are largely reported in Africa, and it is
      compulsory to know the present situation of resistance. The in vivo World Health
      Organization standard 28-day test was used to assess the efficacy of AQ and SP to
      treat uncomplicated falciparum malaria in Gabonese children under 10 years of
      age. To document treatment failures, molecular genotyping to distinguish
      therapeutic failures from reinfections and drug dosages were undertaken. A total
      of 118 and 114 children were given AQ or SP, respectively, and were monitored. SP
      was more effective than AQ, with 14.0 and 34.7% of therapeutic failures,
      respectively. Three days after initiation of treatment, the mean level of
      monodesethylamodiaquine (MdAQ) in plasma was 149 ng/ml in children treated with
      amodiaquine. In those treated with SP, mean levels of sulfadoxine and
      pyrimethamine in plasma were 100 microg/ml and 212 ng/ml, respectively. Levels of
      the three drugs were higher in patients successfully treated with AQ (MdAQ plasma
      levels) or SP (sulfadoxine and pyrimethamine plasma levels). Blood concentration
      higher than breakpoints of 135 ng/ml for MdAQ, 100 micro g/ml for sulfadoxine,
      and 175 ng/ml for pyrimethamine were associated with treatment success (odds
      ratio: 4.5, 9.8, and 11.8, respectively; all P values were <0.009). Genotyping of
      merozoite surface proteins 1 and 2 demonstrated a mean of 4.0 genotypes per
      person before treatment. At reappearance of parasitemia, both recrudescent
      parasites (represented by common bands in both samples) and newly inoculated
      parasites (represented by bands that were absent before treatment) were present
      in the blood of most (51.1%) children. Only 3 (6.4%) therapeutic failures were
      the result not of treatment inefficacy but of new infection. In areas where
      levels of drug resistance and complexity of infections are high, drug dosage and
      parasite genotyping may be of limited interest in improving the precision of drug
      efficacy measurement. Their use should be weighted according to logistical
      constraints.

PMID- 12499197
TI  - Discrepancies between protease inhibitor concentrations and viral load in
      reservoirs and sanctuary sites in human immunodeficiency virus-infected patients.
AB  - The variable penetration of antiretroviral drugs into sanctuary sites may
      contribute to the differential evolution of human immunodeficiency virus (HIV)
      and the emergence of drug resistance. We evaluated the penetration of indinavir,
      nelfinavir, and lopinavir-ritonavir (lopinavir/r) in the central nervous system,
      genital tract, and lymphoid tissue and assessed the correlation with residual
      viral replication. Plasma, cerebrospinal fluid (CSF), semen, and lymph node
      biopsy samples were collected from 41 HIV-infected patients on stable highly
      active antiretroviral therapy regimens to determine drug concentrations and HIV
      RNA levels. When HIV RNA was detectable, sequencing of the reverse transcriptase
      and protease genes was performed. Ratios of the concentration in
      semen/concentration in plasma were 1.9 for indinavir, 0.08 for nelfinavir, and
      0.07 for lopinavir. Only indinavir was detectable in CSF, with a concentration in
      CSF/concentration in plasma ratio of 0.17. Differential penetration into lymphoid
      tissue was observed, with concentration in lymph node tissue/concentration in
      plasma ratios of 2.07, 0.58, and 0.21 for indinavir, nelfinavir, and lopinavir,
      respectively. HIV RNA levels were <50 copies/ml in all CSF samples of patients in
      whom HIV RNA was not detectable in plasma. HIV RNA was detectable in the semen of
      three patients (two patients receiving nelfinavir and one patient receiving
      lopinavir/r), and its detection was associated with multiple resistance
      mutations, while the viral load in plasma was undetectable. HIV RNA was
      detectable in all lymph node tissue samples. Differential drug penetration was
      observed among the three protease inhibitors in the sanctuary sites, but there
      was no correlation between drug levels and HIV RNA levels, suggesting that
      multiple factors are involved in the persistence of viral reservoirs. Further
      studies are required to clarify the role and clinical relevance of drug
      penetration in sanctuaries in terms of long-term efficacy and drug resistance.

PMID- 12499198
TI  - Ribonucleoside analogue that blocks replication of bovine viral diarrhea and
      hepatitis C viruses in culture.
AB  - A base-modified nucleoside analogue, beta-D-N(4)-hydroxycytidine (NHC), was found
      to have antipestivirus and antihepacivirus activities. This compound inhibited
      the production of cytopathic bovine viral diarrhea virus (BVDV) RNA in a dose
      dependant manner with a 90% effective concentration (EC(90)) of 5.4 microM, an
      observation that was confirmed by virus yield assays (EC(90) = 2 microM). When
      tested for hepatitis C virus (HCV) replicon RNA reduction in Huh7 cells, NHC had
      an EC(90) of 5 microM on day 4. The HCV RNA reduction was incubation time and
      nucleoside concentration dependent. The in vitro antiviral effect of NHC was
      additive with recombinant alpha interferon-2a and could be prevented by the
      addition of exogenous cytidine and uridine but not of other natural ribo- or 2'
      deoxynucleosides. When HCV RNA replicon cells were cultured in the presence of
      increasing concentrations of NHC (up to 40 micro M) for up to 45 cell passages,
      no resistant replicon was selected. Similarly, resistant BVDV could not be
      selected after 20 passages. NHC was phosphorylated to the triphosphate form in
      Huh7 cells, but in cell-free HCV NS5B assays, synthetic NHC-triphosphate (NHC-TP)
      did not inhibit the polymerization reaction. Instead, NHC-TP appeared to serve as
      a weak alternative substrate for the viral polymerase, thereby changing the
      mobility of the product in polyacrylamide electrophoresis gels. We speculate that
      incorporated nucleoside analogues with the capacity of changing the
      thermodynamics of regulatory secondary structures (with or without introducing
      mutations) may represent an important class of new antiviral agents for the
      treatment of RNA virus infections, especially HCV.

PMID- 12499199
TI  - Enzymatic assay for measurement of intracellular DXG triphosphate concentrations
      in peripheral blood mononuclear cells from human immunodeficiency virus type 1
      infected patients.
AB  - DXG ([2R-cis]-2-amino-1,9-dihydro-9-[2-[hydroxymethyl]-1,3-dioxolan-4-yl]-6H
      purin-6-one) and its prodrug DAPD ([2R-cis]-4-[2,6-diamino-9H-purin-9-yl]-1,3
      dioxolane-2-methanol; amdoxovir) are novel 2',3'-dideoxynucleosides (ddNs)
      displaying activity against human immunodeficiency virus type 1 (HIV-1). In this
      paper, we describe the development of an enzymatic assay for determining the
      intracellular active metabolite of DXG and DAPD, DXG triphosphate (DXGTP), in
      peripheral blood mononuclear cells (PBMCs) from HIV-infected patients. The assay
      involves inhibition of HIV reverse transcriptase (RT), which normally
      incorporates radiolabeled deoxynucleoside triphosphates (dNTPs) into a synthetic
      template primer. DXGTP (0.6 pmol) inhibited control product formation with or
      without a preincubation step. Inhibition was greatest when the template primer
      was most diluted. DAPDTP inhibited control product formation only at very high
      levels (50 pmol) and when a preincubation procedure was used. However, reduced
      template primer stability in assays using preincubation steps, coupled with
      potential interference by DAPDTP, led to the current assay method for DXGTP being
      performed without preincubation. Standard DXGTP inhibition curves were
      constructed. The presence of PBMC extracts or endogenous dGTP did not interfere
      with the DXGTP assay. Intracellular DXGTP and dGTP concentrations were determined
      in PBMCs from HIV-infected patients receiving oral DAPD (500 mg b.i.d.). Peak
      concentrations of DXGTP were obtained 8 h after dosing and were measurable
      through 48 h postdose. Levels of endogenous dGTP were also determined over 48 h.
      No direct relationship was observed between concentrations of DXGTP and dGTP.
      Quantification of DXGTP concentrations in PBMCs from patients receiving a
      clinically relevant dose of DAPD is possible with this enzymatic assay.

PMID- 12499200
TI  - Synergistic activity of the N-terminal peptide of human lactoferrin and
      fluconazole against Candida species.
AB  - In light of the need for new antifungal regimens, we report that at
      noncandidacidal concentrations, the lactoferrin-derived peptide hLF(1-11), which
      is highly active against fluconazole-resistant Candida albicans, acts
      synergistically with fluconazole against this yeast and a fluconazole-sensitive
      C. albicans strain as well as C. glabrata, C. krusei, C. parapsilosis, and C.
      tropicalis. When these yeasts were exposed to hLF(1-11) for 5 min and then
      incubated with fluconazole, they were killed effectively, while no candidacidal
      activity was observed when they were incubated first with fluconazole and then
      exposed to the peptide, indicating that the candidacidal activity is initiated by
      the peptide while fluconazole is only required during the effector phase.
      Investigations of the effect of azide, which inhibits mitochondrial respiration,
      on the activity of combinations of hLF(1-11) and fluconazole against fluconazole
      resistant C. albicans revealed that it inhibits this activity, even when added
      during the effector phase only. As expected, azide inhibited the accumulation of
      rhodamine 123 in mitochondria and the production and release of ATP by C.
      albicans that occurred upon exposure to the combination of hLF(1-11) and
      fluconazole. Accordingly, oxidized ATP (oATP), an antagonist of ATP receptors,
      completely blocked the candidacidal activity of the hLF(1-11)-fluconazole
      combination, whereas oATP did not block the activity when its presence was
      restricted to the effector phase. The candidacidal activity of combinations of
      hLF(1-11) and fluconazole, which is initiated by the peptide through the
      involvement of energized mitochondria, renders fluconazole-resistant C. albicans
      sensitive to this azole.

PMID- 12499201
TI  - Genetic and functional analysis of the chromosome-encoded carbapenem-hydrolyzing
      oxacillinase OXA-40 of Acinetobacter baumannii.
AB  - Clinical isolate Acinetobacter baumannii CLA-1 was resistant to a series of
      antibiotic molecules, including carbapenems. Cloning and expression of the beta
      lactamase gene content of this isolate in Escherichia coli DH10B identified a
      chromosome-encoded oxacillinase, OXA-40, that differed by one or two amino acid
      changes from OXA-24, -25, and -26 and an AmpC-type cephalosporinase. The OXA-40
      beta-lactamase had a mainly narrow-spectrum hydrolytic profile, but it included
      ceftazidime and imipenem. Its activity was resistant to inhibition by clavulanic
      acid, tazobactam, sulbactam, and, like most of the other carbapenem-hydrolyzing
      oxacillinases, NaCl. OXA-40 had an FGN triad replacing a YGN motif at class D
      beta-lactamase (DBL) positions 144 to 146. Site-directed DNA mutagenesis leading
      to a Phe-to-Tyr change at DBL position 144 in OXA-40 gave a mutant enzyme with
      increased hydrolytic activity against most beta-lactams, including imipenem.
      Conversely, with a gene encoding the narrow-spectrum oxacillinase OXA-1 as the
      template, a nucleotide substitution leading to a Tyr-to-Phe change in the YGN
      motif of OXA-1 gave a mutant enzyme with decreased hydrolytic activity without an
      increase in carbapenem-hydrolyzing activity. Thus, the Phe residue in the FGN
      motif was not associated with carbapenem-hydrolyzing activity by itself but
      instead was associated with weak overall hydrolytic activity. Finally, this Phe
      residue in OXA-40 explained resistance to inhibition by NaCl whereas a Tyr
      residue in motif YGN was related to susceptibility to NaCl.

PMID- 12499202
TI  - Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus
      aureus.
AB  - Gemifloxacin, a novel quinolone with potent activity against Staphylococcus
      aureus, was 8- to 16-fold more active against wild-type S. aureus than
      ciprofloxacin. The two- to fourfold increase in the MIC of gemifloxacin in
      genetically defined grlBA mutants and the twofold increase in a single gyrA
      mutant, supported by the low frequency of selection of resistant mutants at twice
      the MIC (7.4 x 10(-11) to 1.1 x 10(-10)), suggested similar targeting of the two
      enzymes by gemifloxacin. Dual mutations in both gyrase and topoisomerase IV
      caused a 64- to 128-fold increase in the MIC of gemifloxacin, similar to that
      seen with ciprofloxacin. Gemifloxacin also had similar activity in vitro against
      topoisomerase IV and gyrase purified from S. aureus (50% inhibitory
      concentrations of 0.25 and 0.31 micro g/ml, respectively). This activity was 10-
      to 20-fold higher than that of ciprofloxacin for topoisomerase IV and 33-fold
      higher than that for gyrase. In contrast to the in vitro findings, only
      topoisomerase IV mutants were selected in first-step mutants. Overexpression of
      the NorA efflux pump had a minimal effect on resistance to gemifloxacin, and a
      mutation in the promoter region of the gene for NorA was selected only in the
      sixth step of serial selection of mutants. Our data show that although
      gemifloxacin targets purified topoisomerase IV and gyrase similarly in vitro,
      topoisomerase IV is the preferred target in the bacteria. Selection of novel
      resistance mutations in grlA requires further expansion of quinolone-resistance
      determining regions, and their study may provide increased insight into enzyme
      quinolone interactions.

PMID- 12499203
TI  - Roles of Mycobacterium smegmatis D-alanine:D-alanine ligase and D-alanine
      racemase in the mechanisms of action of and resistance to the peptidoglycan
      inhibitor D-cycloserine.
AB  - D-Cycloserine (DCS) targets the peptidoglycan biosynthetic enzymes D-alanine
      racemase (Alr) and D-alanine:D-alanine ligase (Ddl). Previously, we demonstrated
      that the overproduction of Alr in Mycobacterium smegmatis determines a DCS
      resistance phenotype. In this study, we investigated the roles of both Alr and
      Ddl in the mechanisms of action of and resistance to DCS in M. smegmatis. We
      found that the overexpression of either the M. smegmatis or the Mycobacterium
      tuberculosis ddl gene in M. smegmatis confers resistance to DCS, but at lower
      levels than the overexpression of the alr gene. Furthermore, a strain
      overexpressing both the alr and ddl genes displayed an eightfold-higher level of
      resistance. To test the hypothesis that inhibition of Alr by DCS decreases the
      intracellular pool of D-alanine, we determined the alanine pools in M. smegmatis
      wild-type and recombinant strains with or without DCS treatment. Alr
      overproducing strain GPM14 cells not exposed to DCS displayed almost equimolar
      amounts of L- and D-alanine in the steady state. The wild-type strain and Ddl
      overproducing strains contained a twofold excess of L- over D-alanine. In all
      strains, DCS treatment led to a significant accumulation of L-alanine and a
      concomitant decease of D-alanine, with approximately a 20-fold excess of L
      alanine in the Ddl-overproducing strains. These data suggest that Ddl is not
      significantly inhibited by DCS at concentrations that inhibit Alr. This study is
      of significance for the identification of the lethal target(s) of DCS and the
      development of novel drugs targeting the D-alanine branch of mycobacterial
      peptidoglycan biosynthesis.

PMID- 12499204
TI  - Worldwide antimicrobial susceptibility patterns and pharmacodynamic comparisons
      of gatifloxacin and levofloxacin against Streptococcus pneumoniae: report from
      the Antimicrobial Resistance Rate Epidemiology Study Team.
AB  - The use of fluoroquinolones for the treatment of community-acquired respiratory
      tract infection is increasing. Since for Streptococcus pneumoniae a ratio of the
      24-h area under the concentration-time curve (AUC(24)) for the agent to the MIC
      (AUC(24)/MIC) greater than 30 for the fraction of unbound drug (f(u)) is the
      major pharmacokinetic-pharmacodynamic (PK-PD) parameter correlating with
      bacterial eradication by fluoroquinolones in nonclinical models of infection and
      in infected patients, the Antimicrobial Resistance Rate Epidemiology Study Team
      systematically compared the in vitro susceptibility patterns and estimated the
      probability of attainment of the PK-PD target ratios for gatifloxacin and
      levofloxacin against pneumococci worldwide. Monte Carlo simulation was used to
      estimate the probability that gatifloxacin or levofloxacin would achieve an f(u)
      AUC(24)/MIC ratio of 30 or greater. A total of 10,978 S. pneumoniae isolates
      collected from 1997 to 2000, each indexed by site of infection and geographic
      region (North America, Latin America, Europe, and Asia-Pacific), were used to
      estimate the probability mass functions of the microbiological activities for
      each region considered in the analysis. f(u) AUC(24) probability distribution
      functions were estimated by using data that were part of each product's
      submission accepted by the Food and Drug Administration. A 10,000-patient
      simulation was performed for each drug-organism-region combination. The
      percentages of strains susceptible to each drug by region were as follows: for
      gatifloxacin, North America, 99.6%; Latin America, 99.8%; Europe, 99.9%; and Asia
      Pacific, 99.2%; for levofloxacin, North America, 99.6%; Latin America, 99.8%;
      Europe, 99.8%; and Asia-Pacific, 99.1%. The MIC at which 50% of isolates are
      inhibited (MIC(50)) and the MIC(90) of each drug by region were as follows: for
      gatifloxacin, North America, 0.25 and 0.5 mg/liter, respectively; Latin America,
      0.25 and 0.5 mg/liter, respectively; Europe, 0.25 and 0.5 mg/liter, respectively;
      and Asia-Pacific, 0.25 and 0.5 mg/liter, respectively; for levofloxacin, North
      America, 1 and 2 mg/liter, respectively; Latin America, 1 and 2 mg/liter,
      respectively; Europe, 1 and 1 mg/liter, respectively; and Asia-Pacific, 1 and 1
      mg/liter, respectively. The probabilities of attaining an f(u) AUC(24)/MIC ratio
      greater than 30 for each drug by region were as follows: for gatifloxacin, North
      America, 97.6%; Latin America, 98.3%; Europe, 99.1%; and Asia-Pacific, 98.8%; for
      levofloxacin, North America, 78.9%; Latin America, 84.1%; Europe, 87.1%; and Asia
      Pacific, 86.5%. These results for a very large collection of recent clinical
      strains demonstrate that, globally, gatifloxacin is two- to fourfold more active
      than levofloxacin against S. pneumoniae and that gatifloxacin has an overall
      14.3% higher probability of achieving clinically important PK-PD target ratios
      than levofloxacin.

PMID- 12499205
TI  - A type II pathway for fatty acid biosynthesis presents drug targets in Plasmodium
      falciparum.
AB  - It has long been held that the malaria parasite, Plasmodium sp., is incapable of
      de novo fatty acid synthesis. This view has recently been overturned with the
      emergence of data for the presence of a fatty acid biosynthetic pathway in the
      relict plastid of P. falciparum (known as the apicoplast). This pathway
      represents the type II pathway common to plant chloroplasts and bacteria but
      distinct from the type I pathway of animals including humans. Specific inhibitors
      of the type II pathway, thiolactomycin and triclosan, have been reported to
      target this Plasmodium pathway. Here we report further inhibitors of the plastid
      based pathway that inhibit Plasmodium parasites. These include several analogues
      of thiolactomycin, two with sixfold-greater efficacy than thiolactomycin. We also
      report that parasites respond very rapidly to such inhibitors and that the
      greatest sensitivity is seen in ring-stage parasites. This study substantiates
      the importance of fatty acid synthesis for blood-stage parasite survival and
      shows that this pathway provides scope for the development of novel antimalarial
      drugs.

PMID- 12499206
TI  - Reactivity of reduced [2Fe-2S] ferredoxins parallels host susceptibility to
      nitroimidazoles.
AB  - The kinetics of the electron transfer reaction between reduced [2Fe-2S]
      ferredoxins and select nitroimidazole antimicrobial agents is reported. The
      ferredoxins from the protozoan Trichomonas vaginalis and the cyanobacterium
      Anabaena sp. strain 7120 were studied because they are the proximal electron
      donors to nitroimidazoles in these two organisms with significantly different
      nitroimidazole susceptibilities. The rates of electron transfer from Anabaena
      ferredoxin to all nitroimidazoles were 1 to 2 orders of magnitude lower than for
      T. vaginalis ferredoxin. Quantitative structure-activity analysis of the kinetic
      data showed that the size of the alkyl substituent on the N-1 position of the
      imidazole ring strongly influenced the magnitude of the electron transfer rate
      constant. This implies that the distance between the iron-sulfur cluster and the
      nitro group of the imidazole is the critical variable in determining the rate of
      electron transfer. A correlation between the magnitude of the one-electron
      transfer rate constant with the susceptibility of the host organism to the
      cytotoxic effects of nitroimidazoles was also discovered. These results
      demonstrate that reductive activation is the most crucial step in determining the
      toxicity of nitroimidazoles.

PMID- 12499207
TI  - High-throughput growth assay for Toxoplasma gondii using yellow fluorescent
      protein.
AB  - A high-throughput growth assay for the protozoan parasite Toxoplasma gondii was
      developed based on a highly fluorescent transgenic parasite line. These parasites
      are stably transfected with a tandem yellow fluorescent protein (YFP) and are
      1,000 times more fluorescent than the wild type. Parasites were inoculated in
      optical-bottom 384-well culture plates containing a confluent monolayer of host
      cells, and growth was monitored by using a fluorescence plate reader. The signal
      was linearly correlated with parasite numbers over a wide array. Direct
      comparison of the YFP growth assay with the beta-galactosidase growth assay by
      using parasites expressing both reporters demonstrated that the assays'
      sensitivities were comparable but that the accuracy of the YFP assay was higher,
      especially at higher numbers of parasites per well. Determination of the 50%
      inhibitory concentrations of three known growth-inhibiting drugs (cytochalasin D,
      pyrimethamine, and clindamycin) resulted in values comparable to published data.
      The delayed parasite death kinetics of clindamycin could be measured without
      modification of the assay, making this assay very versatile. Additionally, the
      temperature-dependent effect of pyrimethamine was assayed in both wild-type and
      engineered drug-resistant parasites. Lastly, the development of mycophenolic acid
      resistance after transfection of a resistance gene in T. gondii was followed. In
      conclusion, the YFP growth assay limits pipetting steps to a minimum, is highly
      versatile and amendable to automation, and should enable rapid screening of
      compounds to fulfill the need for more efficient and less toxic antiparasitic
      drugs.

PMID- 12499208
TI  - Contributions of antibiotic penetration, oxygen limitation, and low metabolic
      activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and
      tobramycin.
AB  - The roles of slow antibiotic penetration, oxygen limitation, and low metabolic
      activity in the tolerance of Pseudomonas aeruginosa in biofilms to killing by
      antibiotics were investigated in vitro. Tobramycin and ciprofloxacin penetrated
      biofilms but failed to effectively kill the bacteria. Bacteria in colony biofilms
      survived prolonged exposure to either 10 micro g of tobramycin ml(-1)or 1.0 micro
      g of ciprofloxacin ml(-1). After 100 h of antibiotic treatment, during which the
      colony biofilms were transferred to fresh antibiotic-containing plates every 24
      h, the log reduction in viable cell numbers was only 0.49 +/- 0.18 for tobramycin
      and 1.42 +/- 0.03 for ciprofloxacin. Antibiotic permeation through colony
      biofilms, indicated by a diffusion cell bioassay, demonstrated that there was no
      acceleration in bacterial killing once the antibiotics penetrated the biofilms.
      These results suggested that limited antibiotic diffusion is not the primary
      protective mechanism for these biofilms. Transmission electron microscopic
      observations of antibiotic-affected cells showed lysed, vacuolated, and elongated
      cells exclusively near the air interface in antibiotic-treated biofilms,
      suggesting a role for oxygen limitation in protecting biofilm bacteria from
      antibiotics. To test this hypothesis, a microelectrode analysis was performed.
      The results demonstrated that oxygen penetrated 50 to 90 micro m into the biofilm
      from the air interface. This oxic zone correlated to the region of the biofilm
      where an inducible green fluorescent protein was expressed, indicating that this
      was the active zone of bacterial metabolic activity. These results show that
      oxygen limitation and low metabolic activity in the interior of the biofilm, not
      poor antibiotic penetration, are correlated with antibiotic tolerance of this P.
      aeruginosa biofilm system.

PMID- 12499209
TI  - Comparison of anti-hepatitis B virus activities of lamivudine and clevudine by a
      quantitative assay.
AB  - In this study, we used a quantitative assay to measure the concentration
      dependent effects of antivirals on extracellular hepatitis B virus (HBV) DNA as
      well as on different cytoplasmic and nuclear forms of HBV DNA that participate in
      HBV replication. HBV recombinant baculovirus, which efficiently delivers the HBV
      genome to HepG2 cells, was used for this study because (i) antivirals can be
      administered prior to initiation of HBV infection or after HBV infection and (ii)
      sufficiently high HBV replication levels are achieved that HBV covalently closed
      circular (CCC) DNA can be easily detected and individual HBV DNA species can be
      quantitatively analyzed separately from total HBV DNA. The results showed that
      the levels of HBV replicative intermediate and extracellular DNA decreased in a
      concentration-dependent fashion following antiviral treatment. The 50% effective
      concentration (EC(50)) and EC(90) values and the Hill slopes differed for the
      different HBV DNA species analyzed. The data clearly indicated that (i) nuclear
      HBV DNAs are more resistant to antiviral therapy than cytoplasmic or
      extracellular HBV DNAs and (ii) nuclear HBV CCC DNA is more resistant than the
      nuclear relaxed circular form. This report presents the first in vitro comparison
      of the effects of two antivirals administered prior to initiation of HBV
      infection and the first thorough in vitro quantitative study of concentration
      dependent antiviral effects on HBV CCC DNA.

PMID- 12499210
TI  - In vitro activities of daptomycin, vancomycin, quinupristin- dalfopristin,
      linezolid, and five other antimicrobials against 307 gram-positive anaerobic and
      31 Corynebacterium clinical isolates.
AB  - The activities of daptomycin, a cyclic lipopeptide, and eight other agents were
      determined against 338 strains of gram-positive anaerobic bacteria and
      corynebacteria by the NCCLS reference agar dilution method with supplemented
      brucella agar for the anaerobes and Mueller-Hinton agar for the corynebacteria.
      The daptomycin MICs determined on Ca(2+)-supplemented (50 mg/liter) brucella agar
      plates were one- to fourfold lower than those determined in unsupplemented media.
      Daptomycin was highly active (MICs, <or=2 microg/ml) against many strains
      including 36 of 37 peptostreptococci, 37 of 48 isolates of the Eubacterium group,
      and all strains of Propionibacterium spp., Clostridium perfringens, Clostridium
      difficile, and other Clostridium spp. It was fourfold or greater more active than
      vancomycin against Clostridium innocuum and 16 of 34 strains of vancomycin
      resistant lactobacilli. Three strains of C. difficile for which quinupristin
      dalfopristin and linezolid MICs were >8 microg/ml were inhibited by <1 microg of
      daptomycin per ml. Daptomycin MICs were >or=4 microg/ml for most strains of
      Clostridium clostridioforme, Clostridium paraputrificum, Clostridium tertium, and
      Clostridium ramosum; the isolates were generally more resistant to other
      antimicrobials. Daptomycin was two- to fourfold less active against Actinomyces
      spp. than vancomycin, quinupristin-dalfopristin, or linezolid. Twenty-nine of 31
      strains of Corynebacterium spp., including Corynebacterium jeikeium,
      Corynebacterium amycolatum, and Corynebacterium pseudodiphtheriticum, were
      inhibited by <or=0.25 microg of daptomycin per ml. For two strains of
      "Corynebacterium aquaticum," 8 microg of daptomycin per ml was required for
      inhibition. Daptomycin demonstrated very good activities against a broad range of
      gram-positive organisms including vancomycin-resistant C. innocuum and
      lactobacillus strains and quinupristin-dalfopristin- and linezolid-resistant C.
      difficile strains.

PMID- 12499211
TI  - In34, a complex In5 family class 1 integron containing orf513 and dfrA10.
AB  - A complex class 1 integron, In34, found in a conjugative plasmid from a multidrug
      resistant Klebsiella pneumoniae strain isolated in 1997 at a hospital in Sydney,
      Australia, was shown to have a backbone related to that of In2, which belongs to
      the In5 family. In In34, the aadB gene cassette replaces the aadA1a cassette in
      In2, and two additional resistance genes, dfrA10 and aphA1, that are not part of
      a gene cassette are present. The aphA1 gene is in a Tn4352-like transposon that
      is located in the tniA gene. The dfrA10 gene lies adjacent to a 2,154-bp DNA
      segment, known as the common region, that contains an open reading frame
      predicting a product of 513 amino acids (Orf513). Orf513 is 66 and 55% identical
      to the products of two further open reading frames that, like the common region,
      are found adjacent to antibiotic resistance genes. A 27-bp conserved sequence was
      found at one end of each type of common region. The loss of dfrA10 due to
      homologous recombination between flanking direct repeats and incorporation of the
      excised circle by homologous recombination were demonstrated. Part of In34 is
      identical to the sequenced portion of In7, which is from a multidrug-resistant
      Escherichia coli strain that had been isolated 19 years earlier in the same
      hospital. In34 and In7 are in plasmids that contain the same six resistance genes
      conferring resistance to ampicillin, chloramphenicol, gentamicin, kanamycin,
      neomycin, tobramycin, trimethoprim, and sulfonamides, but the plasmid backbones
      appear to be unrelated, suggesting that translocation of a multiple-drug
      resistance-determining region as well as horizontal transfer may have occurred.

PMID- 12499212
TI  - Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination
      with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively
      pretreated human immunodeficiency virus-infected patients.
AB  - The steady-state pharmacokinetics and pharmacodynamics of two oral doses of
      lopinavir-ritonavir (lopinavir/r; 400/100 and 533/133 mg) twice daily (BID) when
      dosed in combination with efavirenz, plus two nucleoside reverse transcriptase
      inhibitors, were assessed in a phase II, open-label, randomized, parallel arm
      study in 57 multiple protease inhibitor-experienced but non-nucleoside reverse
      transcriptase inhibitor-naive human immunodeficiency virus (HIV)-infected
      subjects. All subjects began dosing of lopinavir/r at 400/100 mg BID; subjects in
      one arm increased the lopinavir/r dose to 533/133 mg BID on day 14. When codosed
      with efavirenz, the lopinavir/r 400/100 mg BID regimen resulted in lower
      lopinavir concentrations in plasma, particularly C(min), than were observed in
      previous studies of lopinavir/r administered without efavirenz. Increasing the
      lopinavir/r dose to 533/133 mg increased the lopinavir area under the
      concentration-time curve over a 12-h dosing interval (AUC(12)), C(predose), and
      C(min) by 46, 70, and 141%, respectively. The increase in lopinavir C(max) (33%,)
      did not reach statistical significance. Ritonavir AUC(12), C(max), C(predose),
      and C(min) values were increased 46 to 63%. The lopinavir predose concentrations
      achieved with the 533/133-mg BID dose were similar to those observed with
      lopinavir/r 400/100 mg BID in the absence of efavirenz. Results from univariate
      logistic regression analyses identified lopinavir and efavirenz inhibitory
      quotient (IQ) parameters, as well as the baseline lopinavir phenotypic
      susceptibility, as predictors of antiviral response (HIV RNA < 400 copies/ml at
      week 24); however, no lopinavir or efavirenz concentration parameter was
      identified as a predictor. Multiple stepwise logistic regressions confirmed the
      significance of the IQ parameters, as well as other baseline characteristics, in
      predicting virologic response at 24 weeks in this patient population.

PMID- 12499213
TI  - Activities of moxifloxacin alone and in combination with other antimicrobial
      agents against multidrug-resistant Mycobacterium tuberculosis infection in BALB/c
      mice.
AB  - The activity of moxifloxacin was enhanced by the addition of ethionamide but not
      by that of cycloserine, thiacetazone, capreomycin, para-aminosalicylic acid, or
      linezolid in BALB/c mice infected with a strain of Mycobacterium tuberculosis
      resistant to isoniazid, rifampin, and six other drugs. These observations are
      important for the therapy of multidrug-resistant tuberculosis.

PMID- 12499214
TI  - Clindamycin modulates inflammatory-cytokine induction in lipopolysaccharide
      stimulated mouse peritoneal macrophages.
AB  - We investigated the mechanism by which clindamycin (CLI) modulates cytokine
      induction after lipopolysaccharide (LPS) stimulation. Although CLI decreased the
      intracellular expression levels of tumor necrosis factor alpha and interleukin
      1beta (IL-1beta) and increased IL-6 expression in macrophages, cytokine mRNA
      expression levels were similar in CLI-treated and untreated groups. Our findings
      suggest that CLI modulates cytokine production in LPS-stimulated macrophages.

PMID- 12499215
TI  - Penetration of dihydroartemisinin into cerebrospinal fluid after administration
      of intravenous artesunate in severe falciparum malaria.
AB  - Penetration of cerebrospinal fluid (CSF) by artesunate and DHA was assessed in
      six adults with cerebral or severe malaria. Lumbar punctures were performed on
      admission and during convalescence, at 15 min (patient 1), 30 min (patient 2), 45
      min (patient 3), 60 min (patient 4), 90 min (patient 5), and 120 min (patient 6)
      after intravenous administration of 120 mg of artesunate. No artesunate was
      detectable in CSF. In both studies, DHA levels in CSF increased with time while
      dihydroartemisinin levels in plasma fell. Dihydroartemisinin might accumulate in
      CSF during frequent artesunate dosing.

PMID- 12499216
TI  - Penetration of fosfomycin into inflammatory lesions in patients with cellulitis
      or diabetic foot syndrome.
AB  - We investigated the distribution of the broad-spectrum antibiotic fosfomycin in
      infected soft tissue of patients with uncomplicated cellulitis of the lower
      extremities or diabetic foot infection using in vivo microdialysis. Our findings
      suggest that fosfomycin exhibits good and similar penetration into the fluid in
      the interstitial space in inflamed and noninflamed soft tissue in patients.

PMID- 12499217
TI  - Synergistic lethal effect of a combination of phage lytic enzymes with different
      activities on penicillin-sensitive and -resistant Streptococcus pneumoniae
      strains.
AB  - Pal and Cpl-1, two purified bacteriophage lytic enzymes, were tested for their in
      vitro activity, alone and in combination, against several serotypes of
      Streptococcus pneumoniae, including penicillin-resistant strains. The enzymes
      demonstrated synergism in their ability to cleave the bacterial peptidoglycan and
      thus may be more efficient for the prevention and elimination of pneumococcal
      colonization.

PMID- 12499218
TI  - Drug targeting Mycobacterium tuberculosis cell wall synthesis: development of a
      microtiter plate-based screen for UDP-galactopyranose mutase and identification
      of an inhibitor from a uridine-based library.
AB  - A microtiter plate assay for UDP-galactopyranose mutase, an essential cell wall
      biosynthetic enzyme of Mycobacterium tuberculosis, was developed. The assay is
      based on the release of tritiated formaldehyde from UDP-galactofuranose but not
      UDP-galactopyranose by periodate and was used to identify a uridine-based enzyme
      inhibitor from a chemical library.

PMID- 12499219
TI  - gyrA mutations in ciprofloxacin-resistant Bartonella bacilliformis strains
      obtained in vitro.
AB  - We isolated and characterized mutants of Bartonella bacilliformis that are
      resistant to the fluoroquinolone antibiotic ciprofloxacin, which targets the A
      subunit of DNA gyrase. Mutants had single point mutations in the gyrA gene that
      changed either Asp-90 to Gly or Asp-95 to Asn and had 3- or 16-fold higher
      resistance, respectively, to ciprofloxacin than did wild-type B. bacilliformis.
      Asp-95 is homologous to Asp-87 of Escherichia coli GyrA and is a common residue
      mutated in fluoroquinolone-resistant strains of other bacteria. This is the first
      report of a mutation at an Asp-90 homologue, which corresponds to Asp-82 in E.
      coli GyrA.

PMID- 12499220
TI  - Site-specific mutagenesis analysis of PBP 1A from a penicillin-cephalosporin
      resistant pneumococcal isolate.
AB  - Our mutagenesis study has investigated all amino acid mutations in the penicillin
      binding domain of PBP 1A from Hungarian pneumococcal isolate 3191 to determine
      the importance of every mutation in the development of penicillin and cefotaxime
      resistance. Our data reveal that mutations at amino acid positions 574 to 577 and
      position 539 cause penicillin and cefotaxime resistance.

PMID- 12499221
TI  - In vivo selection of Campylobacter isolates with high levels of fluoroquinolone
      resistance associated with gyrA mutations and the function of the CmeABC efflux
      pump.
AB  - Enrofloxacin treatment of chickens infected with fluoroquinolone(FQ)-sensitive
      Campylobacter promoted the emergence of FQ-resistant Campylobacter mutants which
      propagated in the intestinal tract and recolonized the chickens. The recovered
      isolates were highly resistant to quinolone antibiotics but remained susceptible
      to non-FQ antimicrobial agents. Specific single-point mutations in the gyrA gene
      and the function of the CmeABC efflux pump were linked to the acquired FQ
      resistance. These results reveal that Campylobacter is hypermutable in vivo under
      the selection pressure of FQ and highlight the need for the prudent use of FQ
      antibiotics.

PMID- 12499222
TI  - Escherichia coli with a self-transferable, multiresistant plasmid coding for
      metallo-beta-lactamase VIM-1.
AB  - An Escherichia coli strain exhibiting decreased susceptibility to carbapenems was
      isolated from a hospitalized patient in Greece. The strain carried a self
      transferable plasmid coding for metallo-beta-lactamase VIM-1. bla(VIM-1), along
      with aacA7, dhfrI, and aadA, was included as a gene cassette in a novel class 1
      integron. A Citrobacter freundii ampC-derived gene, not associated with the
      integron, was also located in the same plasmid.

PMID- 12499223
TI  - Comparison of linezolid activities under aerobic and anaerobic conditions against
      methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus
      faecium.
AB  - Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus
      faecium were exposed to linezolid (MIC of 2 mg/liter) under aerobic or anaerobic
      conditions in an in vitro pharmacodynamic model. Drug concentration and half-life
      were adjusted to simulate clinical dosing (600 mg twice daily) of linezolid.
      Linezolid produced a 2-log(10) killing at 24 h, and rates of killing against each
      of these facultative organisms as measured by mean survival time appeared similar
      under aerobic and anaerobic conditions.

PMID- 12499224
TI  - Activities of the glycylcycline tigecycline (GAR-936) against 1,924 recent
      European clinical bacterial isolates.
AB  - The in vitro activities of tigecycline against 1,924 clinical isolates were
      examined. The new glycylcycline exhibited excellent activity against all gram
      positive cocci (MICs at which 90% of the isolates tested were inhibited
      [MIC(90)s], <or=1 microg/ml). In addition, it was also very potent against most
      members of the Enterobacteriaceae, with most MIC(90)s being <or=2 microg/ml.
      Among the nonfermenters, Acinetobacter spp. and Stenotrophomonas maltophilia are
      included in the in vitro spectrum of tigecycline activity.

PMID- 12499225
TI  - Activities of HMR 3787 and RU 64399 compared with those of four other agents
      against Haemophilus influenzae and Haemophilus parainfluenzae.
AB  - Activities of HMR 3787, a new 2-fluoroketolide, and its (des)-fluor derivative,
      RU 64399, were tested against 111 Haemophilus influenzae and 26 H. parainfluenzae
      strains and compared with those of telithromycin, erythromycin, azithromycin, and
      clarithromycin. HMR 3787 and RU 64399 MICs were comparable with those of
      azithromycin but were less affected by incubation in CO(2). Time-kill studies of
      12 strains showed that HMR 3787, RU 64399, and telithromycin were bactericidal
      against all strains after 24 h at two times the MIC.

PMID- 12499226
TI  - Flow cytometric assessment of susceptibilities of Streptococcus pyogenes to
      erythromycin and rokitamycin.
AB  - The effects of erythromycin (a 14-membered ring macrolide) and rokitamycin (a 16
      membered ring macrolide) on the viability of the Streptococcus pyogenes M
      phenotype were studied by means of flow cytometry and fluorescence microscopy by
      using a combination of two fluorochromes (syto 9 and propidium iodide) that
      stains live bacteria green and dead bacteria red. In order to apply the flow
      cytometry, a bacterial sonication procedure was expressly set up to separate
      single cells from the long, intralaced S. pyogenes chains of up to 30 to 40 cells
      that have previously prevented the application of flow cytometry to this type of
      bacteria. The association of flow cytometry using an appropriate sonication
      procedure, together with a combination of fluorescent probes, offered the
      possibility of very quickly investigating the different microbiological effects
      of rokitamycin at 2 microg/ml, which was active on the S. pyogenes M phenotype,
      and of erythromycin at doses of up to 32 microg/ml, which was not.

PMID- 12499227
TI  - Antibiotic susceptibilities of Anaplasma (Ehrlichia) phagocytophilum strains from
      various geographic areas in the United States.
AB  - We tested the antibiotic susceptibilities of eight strains of Anaplasma
      phagocytophilum (the agent of human granulocytic ehrlichiosis) collected in
      various geographic areas of the United States, including Minnesota, Wisconsin,
      California, and New York. The results are homogeneous and show that doxycycline,
      rifampin, and levofloxacin are the most active antibiotics against these strains
      in vitro.

PMID- 12499228
TI  - In vitro activities of linezolid against clinical isolates of Mycobacterium
      tuberculosis that are susceptible or resistant to first-line antituberculous
      drugs.
AB  - We evaluated 117 isolates of Mycobacterium tuberculosis for susceptibility to
      linezolid by the proportion and E-test methods. Linezolid showed high in vitro
      activity, with all the strains inhibited by <or=1 microg of the drug per ml. E
      test MICs were at least 4 dilutions lower than their equivalents by the standard
      proportion method.

PMID- 12499229
TI  - In vitro bactericidal activities of linezolid in combination with vancomycin,
      gentamicin, ciprofloxacin, fusidic acid, and rifampin against Staphylococcus
      aureus.
AB  - The in vitro activities of linezolid were determined alone and in combination
      with vancomycin, ciprofloxacin, gentamicin, fusidic acid, or rifampin against
      five methicillin-susceptible Staphylococcus aureus (MSSA) and five methicillin
      resistant S. aureus (MRSA) strains. Similar responses were obtained against MSSA
      and MRSA. When combined with fusidic acid, gentamicin, or rifampin, linezolid
      prevented selection of resistant mutants but showed no synergy. When linezolid
      was combined with vancomycin and ciprofloxacin, a slight antagonism was observed.
      While the combination with linezolid may reduce the emergence of mutants
      resistant to the associated drugs, the absence of synergy, especially in the case
      of vancomycin and ciprofloxacin, does not argue in favor of such combinations.

PMID- 12499230
TI  - Class 1 integron-borne gene cassettes in multidrug-resistant Yersinia
      enterocolitica strains of different phenotypic and genetic types.
AB  - Seventy nine strains of Yersinia enterocolitica resistant to one or more
      antimicrobials were analyzed for integrons. Only class 1 sul1 integrons
      containing aadA1a (28 strains), aadA1a-dfr1-sat1 (2 strains), and dfr1-aadA1a (1
      strain) gene cassettes were found. The first two types were found in clinical
      isolates belonging to serotype O:3, biotypes 2 to 4, and eight combined
      ribotypes, and the third was found in the reference strain, CECT4054 (O:8). All
      screened resistance markers were found in strains with and without integrons
      (except for chloramphenicol resistance, encoded by catA1 gene, which was only
      present in strains with integrons), but in different resistance profiles (R
      profiles). A profile (ampicillin, streptomycin, sulfadiazine, and trimethoprim
      resistance, encoded by the tem1, aadA1a, sul1, and dfr1 genes, respectively) was
      found in strains, with and without integrons. Integrons and some of the
      resistance genes are located on plasmids with sizes ranging between 65 and 140
      kb. This is the first report of class 1 integrons in Y. enterocolitica.

PMID- 12499231
TI  - Activation and deactivation of a broad-spectrum antiviral drug by a single
      enzyme: adenosine deaminase catalyzes two consecutive deamination reactions.
AB  - Ribavirin is an approved broad-spectrum antiviral drug. A liver-targeting prodrug
      of ribavirin, viramidine, is in clinical trial in an attempt to provide a better
      therapeutic index. The conversion of viramidine to ribavirin, and of ribavirin to
      an inactive metabolite through adenosine deaminase, is reported. Kinetic analysis
      indicates that adenosine deaminase is likely involved in activation of viramidine
      in vivo, and the process is highly pH sensitive. The differential activities of
      two consecutive deamination reactions are kinetically studied and interpreted
      based on adenosine deaminase structural information. A comprehensive
      understanding of the viramidine and ribavirin deamination mechanism should help
      in designing better nucleoside therapeutics in the future.

PMID- 12499232
TI  - Lincomycin resistance mutations in two regions immediately downstream of the -10
      region of lmr promoter cause overexpression of a putative multidrug efflux pump
      in Bacillus subtilis mutants.
AB  - We isolated 19 lincomycin-resistant Bacillus subtilis mutants by expressing lmrB
      encoding a putative multidrug efflux protein. Eighteen of the mutants altered at
      two regions (-3 to -1 and +15) immediately downstream of the -10 region of the
      lmr promoter increased lmr transcription in vivo and in vitro.

PMID- 12499233
TI  - Molecular characterization of quinolone-resistant Neisseria gonorrhoeae in Hong
      Kong.
AB  - In Hong Kong, ParC changes among high-level quinolone-resistant Neisseria
      gonorrhoeae (QRNG) isolates at Ser-87-->Arg were associated with a higher level
      of resistance than a Ser-87-->Ile alteration. Two previously undescribed
      mutations in clinical isolates occurring in gyrA, conferring Ala-92-->Pro and Asp
      95-->Tyr changes, were detected. Nine different outer membrane lipoprotein (Lip)
      repeat classes-11 to 19 repeats-were identified, with repeat lengths of 16 and 17
      the most common, indicating considerable strain diversity.

PMID- 12499234
TI  - Mutant prevention concentration of gemifloxacin for clinical isolates of
      Streptococcus pneumoniae.

PMID- 12499235
TI  - High impact of an expanded restriction fragment length polymorphism assay on
      detection of ganciclovir-resistant UL97 mutants of human cytomegalovirus.

PMID- 12499236
TI  - Moxifloxacin for community-acquired pneumonia.

PMID- 12499237
TI  - Use of macrolides for Q fever.

PMID- 12499239
TI  - P21Waf1 control of epithelial cell cycle and cell fate.
AB  - As a broad-acting cyclin-dependent kinase inhibitor, p21(WAF1) occupies a central
      position in the cell cycle regulation of self-renewing tissues such as oral
      mucosa and skin. In addition to regulating normal cell cycle progression
      decisions, p21(WAF1) integrates genotoxic insults into growth arrest and
      apoptotic signaling pathways that ultimately determine cell fate. As a result of
      its complex interactions with cell cycle machinery and response to mutagenic
      agents, p21(WAF1) also has stage-specific roles in epithelial carcinogenesis.
      Finally, a view is emerging of p21(WAF1) as not merely a cyclin-dependent kinase
      inhibitor, but also as a direct participant in regulating genes involved in
      growth arrest, senescence, and aging, thus providing an additional layer of
      control over matters of the cell cycle. This review discusses these various roles
      played by p21(WAF1) in cell cycle control, and attempts to relate these to
      epithelial cell biology, with special emphasis on keratinocytes.

PMID- 12499240
TI  - The fate of the terminally differentiated chondrocyte: evidence for
      microenvironmental regulation of chondrocyte apoptosis.
AB  - Chondrocytes contained within the epiphyseal growth plate promote rapid bone
      growth. To achieve growth, cells activate a maturation program that results in an
      increase in chondrocyte number and volume and elaboration of a mineralized
      matrix; subsequently, the matrix is resorbed and the terminally differentiated
      cells are deleted from the bone. The major objective of this review is to examine
      the fate of the epiphyseal chondrocytes in the growing bone. Current studies
      strongly suggest that the terminally differentiated epiphyseal cells are deleted
      from the cartilage by apoptosis. Indeed, morphological, biochemical, and end
      labeling techniques confirm that death is through the apoptotic pathway. Since
      the induction of apoptosis is spatially and temporally linked to the removal of
      the cartilage matrix, current studies have examined the apoptogenic activity of
      Ca(2+)-, Pi-, and RGD-containing peptides of extracellular matrix proteins. It is
      observed that all of these molecules are powerful apoptogens. With respect to the
      molecular mechanism of apoptosis, studies of cell death with Pi as an apoptogen
      indicate that the anion is transported into the cytosol via a Na(+/)Pi
      transporter. Subsequently, there is activation of caspases, generation of NO, and
      a decrease in the thiol reserve. Finally, we examine the notion that chondrocytes
      transdifferentiate into osteoblasts, and briefly review evidence for, and the
      rationale of, the transdifferentiation process. It is concluded that specific
      microenvironments exist in cartilage that can serve to direct chondrocyte
      apoptosis.

PMID- 12499241
TI  - Cementum and periodontal wound healing and regeneration.
AB  - The extracellular matrix (ECM) of cementum resembles other mineralized tissues in
      composition; however, its physiology is unique, and it contains molecules that
      have not been detected in other tissues. Cementum components influence the
      activities of periodontal cells, and they manifest selectivity toward some
      periodontal cell types over others. In light of emerging evidence that the ECM
      determines how cells respond to environmental stimuli, we hypothesize that the
      local environment of the cementum matrix plays a pivotal role in maintaining the
      homeostasis of cementum under healthy conditions. The structural integrity and
      biochemical composition of the cementum matrix are severely compromised in
      periodontal disease, and the provisional matrix generated during periodontal
      healing is different from that of cementum. We propose that, for new cementum and
      attachment formation during periodontal regeneration, the local environment must
      be conducive for the recruitment and function of cementum-forming cells, and that
      the wound matrix is favorable for repair rather than regeneration. How cementum
      components may regulate and participate in cementum regeneration, possible new
      regenerative therapies using these principles, and models of cementoblastic cells
      are discussed.

PMID- 12499242
TI  - Salivary (SD-type) cystatins: over one billion years in the making--but to what
      purpose?
AB  - Human saliva contains relatively abundant proteins that are related ancestrally
      in sequence to the cystatin superfamily. Most, although not all, members of this
      superfamily are potent inhibitors of cysteine peptidases. Four related genes have
      been identified, CST1, 2, 4 and 5, encoding cystatins SN, SA, S, and D,
      respectively. CST1, 4, and probably CST5 are now known to be expressed in a
      limited number of other tissues in the body, primarily in exocrine epithelia, and
      the term SD-type cystatin is more appropriate than 'salivary cystatin'. These
      genes are co-ordinately regulated in the submandibular gland during post-natal
      development. The organization of these tissue-specifically-expressed genes in the
      genome, and their phylogeny, indicate that they evolved from an ancestral
      housekeeping gene encoding the ubiquitously expressed cystatin C, and are members
      of a larger protein family. Their relationship to rat cystatin S, a
      developmentally regulated rodent submandibular gland protein, remains to be
      established. In this review, the evolution of the SD-type cystatins in the
      cystatin superfamily, their genomics, expression, and structure-function
      relationships are examined and compared with known cystatin functions, with the
      goal of providing clues to their biological roles.

PMID- 12499243
TI  - Analysis of pulpal reactions to restorative procedures, materials, pulp capping,
      and future therapies.
AB  - Every year, despite the effectiveness of preventive dentistry and dental health
      care, 290 million fillings are placed each year in the United States; two-thirds
      of these involve the replacement of failed restorations. Improvements in the
      success of restorative treatments may be possible if caries management
      strategies, selection of restorative materials, and their proper use to avoid
      post-operative complications were investigated from a biological perspective.
      Consequently, this review will examine pulp injury and healing reactions to
      different restorative variables. The application of tissue engineering approaches
      to restorative dentistry will require the transplantation, replacement, or
      regeneration of cells, and/or stimulation of mineralized tissue formation. This
      might solve major dental problems, by remineralizing caries lesions, vaccinating
      against caries and oral diseases, and restoring injured or replacing lost teeth.
      However, until these therapies can be introduced clinically, the avoidance of
      post-operative complications with conventional therapies requires attention to
      numerous aspects of treatment highlighted in this review.

PMID- 12499244
TI  - Suppression of tumor metastasis by blockade of transforming growth factor beta
      signaling in bone marrow cells through a retroviral-mediated gene therapy in
      mice.
AB  - Transforming growth factor B (TGF-beta) is a potent immunosuppressive cytokine
      that is frequently associated with mechanisms of tumor escape from
      immunosurveillance. We report that transplantation of murine bone marrow (BM)
      expressing a dominant-negative TGF-beta type II receptor (TbetaRIIDN) leads to
      the generation of mature leukocytes capable of a potent antitumor response in
      vivo. Hematopoietic precursors in murine BM from donor mice were rendered
      insensitive to TGF-beta via retroviral expression of the TbetaRIIDN construct and
      were transplanted in C57BL/6 mice before tumor challenge. After i.v.
      administration of 5 x 10(5) B16-F10 murine melanoma cells into TbetaRIIDN-BM
      transplanted recipients, survival of challenged mice at 45 days was 70% (7 of 10)
      versus 0% (0 of 10) for vector-control treated mice, and surviving TbetaRIIDN-BM
      mice showed a virtual absence of metastatic lesions in the lung. We also
      investigated the utility of the TGF-beta-targeted approach in a mouse metastatic
      model of prostate cancer, TRAMP-C2. Treatment of male C57BL/6 mice with
      TbetaRIIDN-BM resulted in the survival of 80% (4 of 5) of recipients versus 0% (0
      of 5) in green fluorescent protein-BM recipients or wild-type controls. Cytolytic
      T-cell assays indicate that a specific T-cell response against B16-F10 cells was
      generated in the TbetaRIIDN-BM-treated mice, suggesting that a gene therapy
      approach to inducing TGF-beta insensitivity in transplanted BM cells may be a
      potent anticancer therapy.

PMID- 12499245
TI  - Eradication of glioblastoma, and breast and colon carcinoma xenografts by Hsp70
      depletion.
AB  - Heat shock protein 70 (Hsp70) is an antiapoptotic chaperone protein highly
      expressed in human tumors. Here we demonstrate that locoregional application of
      adenovirus expressing antisense Hsp70 cDNA (Ad.asHsp70) eradicates orthotopic
      xenografts of glioblastoma and breast carcinoma, as well as s.c. xenografts of
      colon carcinoma in immunodeficient mice. Ad.asHsp70-treated tumors showed massive
      apoptosis-like cell death and recruitment of macrophages. Human monocyte-derived
      macrophages effectively removed the corpses of Ad.asHsp70-treated tumor cells in
      vitro. Interestingly, both tumor cell death and phagocytosis were caspase
      independent. Thus, Hsp70 appears as a promising target for the treatment of
      cancers resistant to classic caspase-mediated apoptosis.

PMID- 12499246
TI  - Prediction of in vivo synergistic activity of antiangiogenic compounds by gene
      expression profiling.
AB  - Angiogenesis, an essential phenotype for tumor formation, requires the
      interaction of many cells within the tumor microenvironment. Therefore,
      successful antiangiogenic therapies must be able to block all of the different
      mechanisms tumors use to induce neovascularization. A major challenge for
      developing such protocols is determining which agents are likely to have the
      highest degree of synergistic activity in vivo. We treated human microvascular
      endothelial cells with six inhibitors of angiogenesis and used microarrays to
      seek divergent patterns of gene expression suggestive of potential synergies. The
      expression profiles of a thrombospondin-mimetic peptide (DI-TSPa) and TNP-470
      (TNP) were very similar, whereas endostatin had a dramatically different profile.
      In vitro, endostatin was synergistically antiangiogenic with either TNP-470 or DI
      TSPa. In vivo, mice bearing Lewis lung carcinoma cells treated with a combination
      of endostatin and either DI-TSPa or TNP-470, at doses that were ineffective when
      used alone, resulted in a marked inhibition of tumor growth and decreased tumor
      angiogenesis. Conversely, animals treated with both DI-TSPa and TNP-470
      demonstrated a modest effect on both tumor growth and angiogenesis. These results
      suggest that even in the absence of a complete mechanistic understanding of how
      these inhibitors work, gene expression profiling may be used to predict
      synergistic antiangiogenic activity and thus maximize their antitumor efficacy.

PMID- 12499248
TI  - Amplification of wild-type K-ras promotes growth of head and neck squamous cell
      carcinoma.
AB  - In contrast to many other tumors of different lineage, oncogenic ras mutations
      are rarely found within head and neck squamous cell carcinoma (HNSCC). On the
      other hand, increased expression of wild-type K-ras in HNSCC tumor material has
      been noticed, but the potential physiological consequences of this observation
      have not yet been experimentally assessed. The current study addresses this issue
      by modulating K-ras expression in HNSCC cell lines and primary keratinocytes and
      determining its effects on cell growth and survival in vitro. Consistent with
      earlier reports using patient tumor material, Western blot analysis of four HNSCC
      lines (SCC-9, SCC-15, SCC-25, and FaDu) revealed varying but universally
      increased protein expression of K-ras relative to keratinocytes. All HNSCC lines
      expressed wild-type K-ras mRNA based on a random sequencing of eight K-ras cDNA
      samples obtained by reverse transcription-PCR from each HNSCC line (P <or=
      0.00391). Transfection of keratinocytes with a plasmid expression vector
      containing wild-type K-ras cDNA resulted in dramatically increased proliferation
      and survival compared with control-transfected or untransfected keratinocytes.
      Conversely, transfection of FaDu cells, which express the highest level of
      endogenous K-ras, with K-ras antisense oligonucleotides but not control
      oligonucleotides significantly reduced cellular proliferation (P <or= 0.0022).
      These results show that the level of K-ras protein expression is a major
      determinant of proliferation of HNSCC cells and keratinocytes and suggest that
      amplification of nonmutated K-ras in HNSCC contributes to tumor growth. These
      novel findings may have important ramifications for potential K-ras-targeted
      interventions in the treatment of HNSCC.

PMID- 12499247
TI  - Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr
      Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571).
AB  - Imatinib mesylate, a selective inhibitor of the Abl tyrosine kinase, is effective
      as a single-agent therapy for chronic myelogenous leukemia. However, resistance
      has been reported, particularly in patients with advanced-stage disease.
      Mutations within the Abl kinase domain are a major cause of resistance,
      demonstrating that Bcr-Abl remains a critical drug target. Recently, a novel
      pyrido[2,3-d]pyrimidine derivative, PD180970, has been shown to potently inhibit
      Bcr-Abl and induce apoptosis in Bcr-Abl-expressing leukemic cells. We analyzed
      the inhibitory activity of PD180970 against Abl kinase domain mutations and cells
      expressing clinically relevant mutations. Our data indicate that PD180970 is
      active against several Bcr-Abl mutations that are resistant to imatinib and
      support the notion that developing additional Abl kinase inhibitors would be
      useful as a treatment strategy for chronic myelogenous leukemia.

PMID- 12499249
TI  - Identification of a candidate oncogene SEI-1 within a minimal amplified region at
      19q13.1 in ovarian cancer cell lines.
AB  - High-level amplification of DNA sequence at 19q13.1 is one of the frequent
      genetic alterations in ovarian cancer. In an attempt to verify the minimal
      amplified region (MAR) at 19q13.1 and to identify the target oncogenes, 49 probes
      within a region from D19S425 to D19S907 ( approximately 19.5 cM) were used to
      survey the amplification status in four ovarian cancer cell lines that have been
      confirmed as containing amplification at 19q13.1. Two separated overlapping MARs,
      MAR1 (approximately 200 kb) and MAR2 (approximately 1.1 Mb), were identified at
      19q13.1. Two candidate oncogenes, AKT2 and SEI-1, were identified in MAR2.
      Amplification and overexpression of these two genes in four ovarian cancer cell
      lines were confirmed by Southern and Northern blot analyses. The proliferation
      related function of AKT2 and SEI-1 suggests that both genes are likely to be
      biological targets of an amplification event at 19q13.1 in ovarian cancer and to
      play important roles in ovarian tumorigenesis.

PMID- 12499250
TI  - High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor
      prognosis in patients with esophageal squamous cell carcinoma.
AB  - Transforming growth factor beta (TGF-beta) regulates growth of various cells, and
      inactivation of the TGF-beta signaling pathway contributes to tumor progression.
      Smad2 is phosphorylated and activated by TGF-beta, resulting in the
      antiproliferative effects of TGF-beta signaling. Smurf2 (Smad ubiquitination
      regulatory factor 2) was identified as the Smad ubiquitin ligase that induces the
      ubiquitination and degradation of Smad2. This study was undertaken to elucidate
      the relationships between Smurf2 expression and the clinicopathological
      characteristics of patients with esophageal squamous cell carcinoma (SCC) and the
      correlation between Smurf2 and Smad2 expression. Surgical specimens obtained from
      80 patients with esophageal SCC were subjected to immunohistochemical staining.
      Our data indicated that high-level expression of Smurf2 correlated with depth of
      invasion, lymph node metastasis, and a poor survival rate. We also found an
      inverse correlation between the expression of Smurf2 and Smad2. Western blotting
      analysis of esophageal SCC-derived cell lines revealed similar inverse
      correlations. We demonstrated that high-level expression of Smurf2 appears to
      correlate with tumor development and poor prognosis in patients with esophageal
      SCC and that alteration of Smad2 expression in the TGF-beta signaling pathway may
      be induced by enhancement of Smad2 degradation mediated by high-level expression
      of Smurf2.

PMID- 12499251
TI  - GFP expression in the mammary gland for imaging of mammary tumor cells in
      transgenic mice.
AB  - To examine the behavior of tumor cells in tumors developing directly from mammary
      tissue in transgenic models, we have evaluated transgenic mice expressing green
      fluorescent protein (GFP). Using the mouse mammary virus promoter (MMTV) to
      directly drive expression of GFP, we find low levels of fluorescence in the
      mammary and salivary glands of transgenic animals. Using MMTV-Cre or WAP-Cre in
      combination with the Cre-activatable CAG-CAT-EGFP construct, we find stronger
      expression of GFP that is still tissue specific. These animals provide a range of
      expression of GFP that is suitable for analysis of transgenic mammary tumors and
      metastases in vivo at the single cell level of resolution.

PMID- 12499253
TI  - Feline immunodeficiency virus integration in B-cell lymphoma identifies a
      candidate tumor suppressor gene on human chromosome 15q15.
AB  - Infection with immunosuppressive lentiviruses is associated with increased cancer
      risk,but most studies have implicated indirect mechanisms as the tumor cells
      generally lack integrated viral sequences. An exception wasfound in a B-cell
      lymphoma (Q254) where the tumor cells contained a single integrated feline
      immunodeficiency virus genome. Additional analysis now indicates that feline
      immunodeficiency virus integration in lymphoma Q254 resulted in promoter
      insertion and truncation of a conserved gene on feline chromosome B3, whereas the
      unaffected allele of the gene appeared to be transcriptionally down-regulated.
      The orthologous human gene (FLJ12973), is expressed ubiquitously and encodes a WD
      repeat protein with structural similarity to DDB2, the small subunit of the
      xeroderma pigmentosum XP-E complex. Moreover, the gene is located within a region
      of frequent tumor-specific deletions on chromosome 15q15. These observations
      demonstrate the direct mutagenic potential of the lentiviruses and identify a new
      candidate tumor suppressor gene.

PMID- 12499252
TI  - Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of
      tumor necrosis factor-related apoptosis-inducing ligand.
AB  - Current therapies for gliomas fail to address their highly infiltrative nature.
      Standard treatments often leave behind microscopic neoplastic reservoirs,
      resulting in eventual tumor recurrence. Neural stem cells (NSCs) are capable of
      tracking disseminating glioma cells. To exploit this tropism to develop a
      therapeutic strategy that targeted tumor satellites, we inoculated human
      glioblastoma xenografts with tumor necrosis factor-related apoptosis-inducing
      ligand-secreting NSCs. This resulted in the dramatic induction of apoptosis in
      treated tumors and tumor satellites and was associated with significant
      inhibition of tumor growth. These results add credence to the potential of NSCs
      as therapeutically effective delivery vehicles for the treatment of intracranial
      glioma.

PMID- 12499254
TI  - Proviral insertion indicates a dominant oncogenic role for Runx1/AML-1 in T-cell
      lymphoma.
AB  - The RUNX1/AML1 gene is a frequent target for chromosomal translocations in human
      leukemia. The biological properties of the resulting fusion products and the
      finding that haploinsufficiency increases the risk of developing leukemia (W-J.
      Song et al., Nat. Genet., 23: 166-175, 1999; M. Osata et al., Blood, 93: 1817
      1824, 1999) have led to the widely held view that RUNX1 loss-of-function is a key
      event. However, we now report that the gene is a target for insertional
      mutagenesis in T-cell lymphomas of mice carrying a MYC oncogene, where promoter
      insertion results in overexpression without affecting the integrity of the coding
      sequence. Moreover, Runx1 haploinsufficiency does not accelerate lymphoma
      development in MYC/Runx2 transgenic or murine leukemia virus-infected mice. These
      findings reveal that the Runx1 gene can also act as a dominant oncogene and
      suggest that the involvement of the Runx gene family in human leukemia may be
      more widespread and complex than previously realized.

PMID- 12499255
TI  - Significantly high levels of ultraviolet-specific mutations in the smoothened
      gene in basal cell carcinomas from DNA repair-deficient xeroderma pigmentosum
      patients.
AB  - The Sonic hedgehog (SHH) pathway is implicated in the etiology of the most common
      human cancer in Caucasians, the basal cell carcinoma (BCC). Mutations in the
      receptor of SHH, the patched gene, have been characterized in sporadic BCCs as
      well as those from patients with the rare genetic syndromes nevoid BCC and
      xeroderma pigmentosum (XP). To elucidate the role of UV in the deregulation of
      the SHH pathway, we analyzed for alterations of smoothened, a transmembrane
      signaling component regulated by patched, in BCCs and squamous cell carcinomas
      from UV hypersensitive XP patients. We find UV-specific smoothened mutations in
      30% of XP BCCs, three times higher than those in sporadic Caucasian BCCs,
      confirming the high rate of UV-induced mutations in DNA repair-deficient XP
      patients. No alteration was found in XP squamous cell carcinomas, indicating the
      involvement of smoothened specifically in the development of BCC.

PMID- 12499256
TI  - Internalizing antibodies are necessary for improved therapeutic efficacy of
      antibody-targeted liposomal drugs.
AB  - Direct experimental proof has been sought for the hypothesis that liposomal drugs
      targeted against internalizing epitopes (e.g., CD19) will have higher therapeutic
      efficacies than those targeted against noninternalizing epitopes (e.g., CD20).
      Anti-CD19-targeted liposomes were rapidly internalized into human B-lymphoma
      (Namalwa) cells, whereas those targeted with anti-CD20 were not internalized.
      Similar in vitro binding and cytotoxicity were observed for anti-CD19-targeted
      and anti-CD20-targeted liposomal formulations of doxorubicin (DXR). Therapeutic
      experiments were performed in severe combined immunodeficient mice inoculated
      i.v. with Namalwa cells. Administration of single i.v. doses of DXR-loaded anti
      CD19-targeted liposomes resulted in significantly greater survival times than
      either DXR-loaded anti-CD20-targeted liposomes or nontargeted liposomes. The
      therapeutic advantage of targeting internalizing versus noninternalizing epitopes
      has been directly demonstrated.

PMID- 12499257
TI  - Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4(+) T
      cells.
AB  - The EBV-encoded nuclear antigen 1 (EBNA1) is required for the maintenance and
      replication of the viral episome in EBV-transformed human B-lymphoblastoid cell
      lines. It is expressed in all EBV-associated tumors, making it a potentially
      important target for immunotherapy. However, this promise has not been realized,
      because an endogenously processed MHC class I-restricted T-cell epitope remains
      to be identified, and relatively little is known about MHC class II-restricted
      helper epitopes in the molecule. In this report, we identify a T-cell peptide
      derived from EBNA1 that is recognized by CD4(+) T cells. More importantly, EBNA1
      specific, HLA-DP3-restricted CD4(+) T cells are capable of recognizing MHC class
      II-matched Burkitt's lymphoma cells, autologous peripheral blood mononuclear
      cells loaded with the purified EBNA1 protein, as well as target cells transfected
      with Ii-EBNA1 cDNA. These new findings demonstrate that EBNA1 is processed
      endogenously and presented to T cells by MHC class II molecules, and, hence, may
      be useful to incorporate into cancer vaccines to enhance antitumor immunity
      against EBV-associated tumors.

PMID- 12499258
TI  - Potential for the 2G single nucleotide polymorphism in the promoter of matrix
      metalloproteinase to enhance gene expression in normal stromal cells.
AB  - The 1G/2G polymorphism of matrix metalloproteinase 1 (MMP-1) affects activity of
      the promoter in transient transfections, and has been associated with the
      incidence or invasiveness of five types of cancer. In light of these findings,
      and because stromal cells may contribute to tumor cell invasion, we used
      quantitative real-time reverse transcription-PCR to measure endogenous MMP-1 mRNA
      expression in 34 human foreskin fibroblasts homozygous or heterozygous for the 1G
      and 2G alleles. We measured basal, cytokine, and growth factor induced MMP-1 mRNA
      expression. The genotype of the MMP-1 promoter polymorphism was not predictive of
      mean MMP-1 mRNA expression. However, within the population of cell lines with at
      least one 2G polymorphism, there were more individuals with higher levels of MMP
      1 mRNA after treatment with a cytokine or growth factors. Our data suggest that
      the presence of the 2G polymorphism does not significantly affect mean expression
      levels of a population but may increase the potential for an individual to have
      higher MMP-1 expression in response to growth factors and cytokines.

PMID- 12499259
TI  - Vascular endothelial growth factor promotes breast carcinoma invasion in an
      autocrine manner by regulating the chemokine receptor CXCR4.
AB  - We report that vascular endothelial growth factor (VEGF), a major angiogenic
      factor, is also arequisite autocrine factor for breast carcinoma invasion in
      vitro and that the VEGF receptor Neuropilin-1 but not Flt-1 is essential for this
      function. VEGF regulates expression of the chemokine receptor CXCR4, and this
      VEGF target is needed for invasion but not for cell survival. CXCR4 mediates
      migration of breast carcinoma cells toward stromal-derived factor-1, and this
      migration is dependent on autocrine VEGF. Of interest, a CXCR4-inhibitory peptide
      that is currently in HIV clinical trials suppressed invasion. Our findings
      indicate that a VEGF autocrine pathway induces chemokine receptor expression in
      breast carcinoma cells, thus promoting their directed migration toward specific
      chemokines.

PMID- 12499260
TI  - Cancer-inducible transgene expression by the Grp94 promoter: spontaneous
      activation in tumors of various origins and cancer-associated macrophages.
AB  - A major challenge in treating cancer is the difficulty of bringing therapy to
      poorly perfused areas of solid tumors, which are often most resistant to
      chemotherapy and radiation. GRP94 is a chaperone protein localized in the
      endoplasmic reticulum with antiapoptotic properties. We report here that in vitro
      the proximal murine grp94 promoter is regulated differently from the hypoxia
      response element fused to the SV40 minimal promoter, with glucose starvation as
      an inducer of grp94 but a potent repressor of the hypoxia response element/SV40
      fusion promoter. Through the use of transgenic mouse models, we showed that LacZ
      transgene expression driven by the grp94 promoter was strongly activated not only
      in spontaneous but also in a variety of chemically induced tumors. We
      additionally discovered that macrophages in the vicinity of malignant tumor
      showed a high level of transgene expression, consistent with intense beta
      galactosidase staining at boundaries between viable tumor cells and necrotic
      areas. Isolated macrophages also showed grp94 mRNA and transgene activation under
      glucose starvation in vitro. In contrast, transgene activity was not detected in
      the normal tissue counterparts of any of the malignant tumors examined or
      macrophages associated with normal organs. These studies provide direct evidence
      that the tumor microenvironment is a potent physiological inducer of the grp94
      promoter. The unique properties of the grp94 promoter suggest that it may offer a
      novel tool for directing transcription of therapeutic agents to tumors
      particularly in resistant regions bordering necrotic areas, delivered through
      standard vectors or macrophages.

PMID- 12499261
TI  - Dependence of histone modifications and gene expression on DNA hypermethylation
      in cancer.
AB  - We examined the relationship between aberrant DNA hypermethylation and key
      histone code components at a hypermethylated, silenced tumor suppressor gene
      promoter in human cancer. In lower eukaryotes, methylated H3-lysine 9 (methyl-H3
      K9) determines DNA methylation and correlates with repressed gene transcription.
      Here we show that a zone of deacetylated histone H3 plus methyl-H3-K9 surrounds a
      hypermethylated, silenced hMLH1 promoter, which, when unmethylated and active, is
      embedded in methyl-H3-K4 and acetylated H3. Inhibiting DNA methyltransferases,
      but not histone deacetylases, leads first to promoter demethylation, second to
      gene reexpression, and finally to complete histone code reversal. Our findings
      suggest a new paradigm-DNA methylation may directly, or indirectly by inhibiting
      transcription, maintain key repressive elements of the histone code at a
      hypermethylated gene promoter in cancer.

PMID- 12499262
TI  - Distribution of furamidine analogues in tumor cells: targeting of the nucleus or
      mitochondria depending on the amidine substitution.
AB  - Diphenylfuran diamidines represent an important class of DNA minor groove binders
      of high therapeutic interest as antiparasitic or antitumor agents depending on
      the compounds structures. To exert their cytotoxic action, the compounds must
      first get into the cell and reach the nuclear compartment where the main target,
      DNA, is located. The forces that drive the drugs into cell nuclei, as well as the
      influence of the molecular structures on the cell distribution, are not known. To
      address these issues, we took advantage of the fluorescence of the molecules to
      analyze their intracellular distribution profiles in tumor cells of different
      origins (B16 melanoma, MCF7 mammary adenocarcinoma, A549 lung carcinoma, HT29
      colon carcinoma, LNCaP, and PC3 prostatic carcinoma) by epifluorescence and
      confocal microscopy. A homogeneous series of synthetic bis-substituted alkyl or
      phenyl amidine and reverse amidine derivatives of furamidine was used to dissect
      the molecular mechanisms that control the distribution of the drugs into the
      cytoplasm or the nucleus of the cells. The amidine (DB75) and the various N-alkyl
      derivatives were found to accumulate selectively in the cell nuclei. This is also
      the case for a guanidine derivative but not for the phenyl-substituted compound
      DB569, which essentially localizes in cytoplasmic granules. Similar cytoplasmic
      patterns were observed with a reverse amidine analogue and a pyridine-substituted
      compound indicating that the presence of aromatic rings on the terminal side
      chain is the limiting factor that restricts the uptake of the compounds in the
      nuclear compartment. The use of different organelle-selective fluorescent probes,
      such as JC-1 and chloromethyl-X-rosamine, both specific to mitochondria and
      neutral red considered as a lysosome-selective probe, suggests that DB569
      preferentially accumulates in mitochondria. Competition experiments with the
      antitumor drug daunomycin reveal that the diphenylfurans are attracted into the
      nuclei by the DNA. The DNA minor groove-drug interactions provide the driving
      force that permits massive accumulation of the fluorescent molecules in the
      nuclei. The DNA binding properties of the diphenylfuran derivatives were
      investigated by DNase I footprinting and surface plasmon resonance biosensor
      experiments to measure sequence selectivity and binding affinities, respectively.
      Furamidine and its phenyl-substituted analogue that accumulate in the cell nuclei
      and mitochondria, respectively, share a common selectivity for AT sites and bind
      equally tightly to these sites. Therefore, it is possible to modulate the
      intracellular distribution of the furamidine derivatives without affecting their
      DNA binding and sequence recognition properties. The introduction of aromatic
      substituents on diphenylfuran diamidines represents a novel strategy to control
      the intracellular compartmentalization of these DNA binding agents and directs
      them to mitochondria. This drug design strategy may prove useful to trigger drug
      induced apoptosis.

PMID- 12499263
TI  - 8-Hydroxyguanosine repair is defective in some microsatellite stable colorectal
      cancer cells.
AB  - Mutator phenotypes are involved in the carcinogenesis of some cancers, e.g.,
      defects in mismatch repair produce a mutator phenotype that drives carcinogenesis
      and causes microsatellite instability in hereditary nonpolyposis colon cancers
      and some sporadic colorectal cancers (CRC). Less understood, however, is the
      potential role of mutator phenotypes in microsatellite stable (MSS) CRC
      carcinogenesis. A novel transversion mutator phenotype was reported recently in
      an MSS CRC cell line. We hypothesized that 8-hydroxyguanosine could be involved
      and found elevations in 5 of 15 (33%) MSS CRC cell lines analyzed. Repair of an
      adenine*8-hydroxyguanosine mispair was functionally defective in the same five
      cell lines. The human MutY homologue transcript and MutY homologue protein levels
      were also decreased. These findings may reflect a MSS mutator phenotype
      contributing to the development of CRC.

PMID- 12499264
TI  - Both E7 and CpG-oligodeoxynucleotide are required for protective immunity against
      challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells:
      involvement of CD4+ and CD8+ T cells in protection.
AB  - An important goal of immunotherapy against human papillomavirus (HPV) infection
      and the cervical cancer is to control viral infection and the cancer cell growth.
      Here we investigate the utility of HPV 16 E7 along with CpG-oligodeoxynucleotide
      (ODN) for protection against HPV-immortalized tumor cells using an animal model.
      E7+ODN coinjection showed a significant suppression of tumor growth at both
      prophylactic and therapeutic levels. However, no such effect was observed without
      addition of both E7 and ODN. We additionally evaluated levels of immune responses
      by E7+ODN coinjection. E7+ODN resulted in E7-specific antibody (IgG1, IgG2a,
      IgG2b, and IgG3) and T-helper cell proliferative responses significantly higher
      than E7 alone. However, CTL responses were induced only by E7+ODN. Moreover, IFN
      gamma production was detected only in E7+ODN immunized groups in which IFN-gamma
      releasing CD4+ (T-helper 1 type) and CD8+ T cells (CTL) were induced only by
      E7+ODN. Moreover, tumor protection appears to be mediated by CD4+ and in most
      CD8+ T cells, as determined by in vivo T-cell subset depletion. Taken together,
      these data suggest that E7+ODN codelivery could be an effective approach to
      induce E7-specific protective immune responses as a possible immunotherapeutic
      strategy for cervical cancer.

PMID- 12499265
TI  - Stability, cellular uptake, biotransformation, and efflux of tea polyphenol (-)
      epigallocatechin-3-gallate in HT-29 human colon adenocarcinoma cells.
AB  - The biological effects of (-)-epigallocatechin-3-gallate (EGCG) have been
      extensively investigated in cell lines, but its stability and interactions with
      cells under culture conditions are unclear. In the present study, the stability,
      uptake, biotransformation, and efflux of [(3)H]EGCG in HT-29 human colon
      adenocarcinoma cells were investigated. EGCG was unstable in McCoy's 5A culture
      media with a half-life of less than 30 min, and the half-life increased to 130
      min in the presence of cells. The major oxidative products were theasinensin
      (M(r) 914) and another dimer with M(r) 884. Addition of EGCG (50 micro M) to cell
      culture media caused the production of H(2)O(2) (up to 25 micro M), and the
      amount was lower and gradually decreased in the presence of cells. The uptake of
      EGCG was concentration dependent and did not plateau, even at 640 micro M,
      suggesting a passive diffusion process. Approximately 75% of the [(3)H]EGCG was
      found in the cytoplasmic fraction when the cells were incubated with 0.5-20 micro
      M [(3)H]EGCG for 15 min. The membrane-associated radioactivity increased with
      time, apparently because of the binding of dimers to the membrane. The
      accumulation of [(3)H]EGCG in the cells was significantly higher at 4 degrees C
      than at 37 degrees C. Multidrug-resistant protein inhibitors, such as
      indomethacin and probenecid, effectively increased the accumulation of EGCG 4"
      glucuronide and 4"-methyl EGCG in the cell. These results suggest that EGCG is
      metabolized in the cell and that the metabolites are pumped out by MRPs. The
      present study provides fundamental information on the stability, uptake,
      biotransformation, and efflux of EGCG under cell culture conditions and suggests
      the need for careful interpretation of related results on the biological
      activities of EGCG.

PMID- 12499266
TI  - ZD6126: a novel vascular-targeting agent that causes selective destruction of
      tumor vasculature.
AB  - Physiological differences between tumor and normal vasculature provide a target
      for drug discovery. In particular, the immature nature of tumor vasculature may
      render it intrinsically sensitive to disruption by agents affecting the
      endothelial cell cytoskeleton, including tubulin-binding agents. In this article,
      we report the synthesis of a water-soluble phosphate prodrug, ZD6126, of the
      tubulin-binding agent N-acetylcolchinol. In vitro studies demonstrate the
      comparative tubulin-binding properties of the prodrug and active drug, and show
      the induction of pronounced, reversible changes in endothelial cell morphology at
      subcytotoxic doses. Neither ZD6126 nor N-acetylcolchinol showed effects on the
      growth of human umbilical vein endothelial cells at concentrations below 100
      micro M. In contrast, changes in endothelial cell morphology were seen at much
      lower, noncytotoxic concentrations (0.1 micro M) of ZD6126 and more pronounced
      effects were seen in proliferating versus confluent endothelial cell cultures. In
      vivo studies were carried out using a murine tumor model (CaNT) with single
      administration of a dose well below the maximum tolerated dose. These studies
      showed a large reduction in vascular volume, induction of extensive necrosis in
      tumors, and a reduced tumor cell yield in a clonal excision assay, consistent
      with vascular rather than cytotoxic effects. A viable rim of tumor remained after
      single-dose administration and minimal growth delay was observed. However, well
      tolerated, multiple administration regimens led to pronounced tumor-growth delay.
      In the human xenograft FaDu, the growth delay given by a single dose of
      paclitaxel was enhanced by combination with a single dose of ZD6126, and the
      growth delay given by the combination was greater than the sum of the growth
      delays from the individual treatments. These findings show that ZD6126 is a
      promising antivascular agent for the treatment of solid tumors.

PMID- 12499267
TI  - Cancer immunotherapy with interleukin 12 and granulocyte-macrophage colony
      stimulating factor-encapsulated microspheres: coinduction of innate and adaptive
      antitumor immunity and cure of disseminated disease.
AB  - Tumor cells, injected s.c., were maintained until spontaneous metastases to the
      lungs were established in all of the mice. Mice were then treated with a single
      dose of cytokine-encapsulated biodegradable microspheres injected directly into
      primary s.c. tumors to achieve a local and sustained release of interleukin 12
      (IL-12), granulocyte-macrophage colony-stimulating factor (GM-CSF), or a
      combination of these cytokines to the tumor microenvironment. The s.c. tumors
      were surgically excised 6 days after microsphere injections, and the mice were
      monitored for recurrence of the primary tumor, survival, and progression of
      metastatic disease. Combined neoadjuvant treatment with IL-12 and GM-CSF
      microspheres was superior to all other treatments in reducing the recurrence of
      primary tumors, enhancing postoperative survival, and suppressing established
      metastatic disease. Long-term survival analysis demonstrated that intratumoral
      injection of IL-12 + GM-CSF-loaded microspheres resulted in the complete cure of
      disseminated disease in the majority of the animals. The addition of systemic low
      dose IL-2 therapy to the treatment protocol resulted in the loss of the antitumor
      activity induced by IL-12 + GM-CSF treatment. In vivo lymphocyte subset
      depletions established that both T- and natural killer-cell subsets were required
      for the suppression of primary and metastatic tumors. Long-term, tumor-specific T
      cell activity was demonstrated by immunohistochemical analysis of metastatic
      lesions, IFN-gamma enzyme-linked immunosorbent spot (ELISPOT) assays and tumor
      challenge studies. These results establish that neoadjuvant in situ tumor
      immunotherapy with IL-12 + GM-CSF microspheres induces both innate and adaptive
      antitumor immune responses resulting in the eradication of disseminated disease.

PMID- 12499268
TI  - Reexpression of the tumor suppressor gene ARHI induces apoptosis in ovarian and
      breast cancer cells through a caspase-independent calpain-dependent pathway.
AB  - ARHI, an imprinted putative tumor suppressor gene, encodes a M(r) 26,000 GTP
      binding protein that is 60% homologous to ras and rap but has a dramatically
      different function. ARHI expression is down-regulated in a majority of breast and
      ovarian cancers. Using a dual adenovirus system, we have reexpressed ARHI in
      ovarian cancer and breast cancer cells that have lost ARHI expression.
      Reexpression of ARHI inhibited growth, decreased invasiveness, and induced
      apoptosis. At 5 days after infection with ARHI adenovirus, 30-45% of MDA-MB-231
      breast cancer cells and 5-11% of SKOv3 ovarian cancer cells were apoptotic as
      judged by a terminal deoxynucleotidyl transferase-mediated nick end labeling
      assay and by Annexin V staining with flow cytometric analysis. Although poly(ADP
      ribose) polymerase could be detected immunohistochemically in the nuclei of
      apoptotic cells, no activation of the effector caspases (caspase 3, 6, 7, or 12)
      or the initiator caspases (caspase 8 or 9) could be detected in cell lysates
      using Western blotting. When gene expression was analyzed on a custom cDNA array
      that contained 2304 known genes, infection with ARHI adenovirus up-regulated 15
      genes relative to control cells infected with LacZ adenovirus. The greatest
      degree of mRNA up-regulation was observed in a Homo sapiens calpain-like
      protease. On Western blot analysis, calpain protein was increased 2-3-fold at 3-5
      days after infection with ARHI adenovirus. No increase in calpain protein was
      observed after LacZ adenovirus infection. Calpain cleavage could be detected
      after ARHI reexpression, and inhibitors of calpain, but not inhibitors of
      caspase, partially prevented ARHI-induced apoptosis. Consequently, reexpression
      of ARHI in breast and ovarian cancer cells appears to induce apoptosis through a
      caspase-independent, calpain-dependent mechanism.

PMID- 12499269
TI  - Photodynamic therapy creates fluence rate-dependent gradients in the intratumoral
      spatial distribution of oxygen.
AB  - In photodynamic therapy (PDT), treatment efficacy may be reduced by the presence
      of pre-existing tumor hypoxia or by oxygen depletion during the therapy. Tumor
      oxygenation during PDT has been measured with needle electrodes, but the
      intratumoral distribution of this oxygen is not known. In the present study, the
      spatial distribution of hypoxia during PDT was quantified using the hypoxia
      labeling marker EF3. Mice bearing radiation-induced fibrosarcoma tumors were
      treated with Photofrin-mediated PDT to a total dose of 135 J/cm(2), delivered at
      a fluence rate of either 75 mW/cm(2) or 38 mW/cm(2). PDT-created hypoxia at each
      fluence rate was labeled by exposing tumors to EF3 (52 mg/kg) during the period
      of illumination. Cryosectioning, immunohistochemistry, and fluorescence
      microscopy were carried out to quantify EF3 binding as a function of distance to
      the nearest perfused blood vessels in sections cut from within the superficial
      (light-adjacent) 600 micro m or the deep (light-distant) 600 micro m of tumors (5
      6 mm in diameter, approximately 3 mm in depth). In both superficial and deep
      sections, PDT at 75 mW/cm(2) resulted in the development of significant gradients
      in tumor hypoxia as a function of distance to a perfused blood vessel.
      Furthermore, significant hypoxia was detected even in vascular-adjacent tissue.
      These effects were associated with a significant decrease in the percentage of
      perfused vessels and a significant increase in the median distance of a cell to
      the nearest perfused blood vessel. In contrast, during PDT at 38 mW/cm(2),
      sections from deep tumor levels demonstrated only insignificant increases in the
      rise in hypoxia as a function of distance to a perfused vessel and in the level
      of hypoxia in vascular-adjacent tissue. No effects on tumor perfusion were
      detected during PDT at 38 mW/cm(2). Overall, these results demonstrate that
      spatially dependent depletion of oxygen can occur during PDT as a function of the
      fluence rate and that PDT can create significant hypoxia in even tissue adjacent
      to perfused blood vessels.

PMID- 12499270
TI  - Ultrasonically activated chemotherapeutic drug delivery in a rat model.
AB  - Systemic delivery of anticancer agents is accompanied by many unwanted side
      effects that can be mitigated by encapsulation of antineoplastic agents. However,
      encapsulation necessitates a technique for controlled delivery to the cancerous
      tissue. We have developed a novel drug delivery system that releases drug from
      stabilized micelles upon application of low-frequency ultrasound and that
      demonstrates efficacy using doxorubicin (Dox) to treat tumors in vivo. Forty-two
      BDIX rats were inoculated in each hind leg with a DHD/K12/TRb tumor cell line.
      Dox was encapsulated within stabilized Pluronic micelles and administered weekly
      i.v. to the rats starting 6 weeks after the tumor inoculations. One of the two
      tumors was exposed to low-frequency ultrasound for 1 h. Dox concentrations of
      1.33, 2.67, and 8 mg/kg and ultrasound frequencies of 20 and 70 kHz were used for
      treatment. Tumor volume was measured with calipers and observed over the
      treatment time. Administration of encapsulated Dox at concentrations of 1.33 and
      2.67 mg/kg was not lethal to the rats. Application of low-frequency ultrasound
      (both 20 and 70 kHz) significantly reduced the tumor size when compared with
      noninsonated controls (P = 0.0062) in the other leg for rats receiving
      encapsulated Dox. Significant tumor reduction was also noted for those rats
      receiving ultrasound and encapsulated Dox at 2.67 mg/kg (P = 0.017) and rats
      receiving Dox and ultrasound at 70 kHz (P = 0.029). We postulate that ultrasound
      releases the Dox from the micelles as they enter the insonated volume, and
      ultrasound could also assist the drug and/or carriers to extravasate and enter
      the tumor cells. Encapsulation of Dox using stabilized Pluronic micelles and
      localized release using low-frequency ultrasound show promise in offering
      controlled drug delivery in the treatment of tumors in a rat model.

PMID- 12499271
TI  - ZD6474, an orally available inhibitor of KDR tyrosine kinase activity,
      efficiently blocks oncogenic RET kinases.
AB  - RET/papillary thyroid carcinoma (PTC) oncogenes, generated by recombination of
      the tyrosine kinase-encoding domain of RET with different heterologous genes, are
      prevalent in papillary carcinomas of the thyroid. Point mutations of RET cause
      multiple endocrine neoplasia type 2 (MEN2) familial cancer syndrome and are found
      in sporadic medullary thyroid carcinomas. Here, we show that ZD6474, a low
      molecular weight tyrosine kinase inhibitor, blocks the enzymatic activity of RET
      derived oncoproteins at a one-half maximal inhibitory concentration of 100 nM.
      ZD6474 blocked in vivo phosphorylation and signaling of the RET/PTC3 and
      RET/MEN2B oncoproteins and of an epidermal growth factor (EGF)-activated EGF
      receptor/RET chimeric receptor. RET/PTC3-transformed cells-treated ZD6474 lost
      proliferative autonomy and showed morphological reversion. ZD6474 prevented the
      growth of two human PTC cell lines that carry spontaneous RET/PTC1
      rearrangements. Finally, it blocked anchorage-independent growth of RET/PTC3
      transformed NIH3T3 fibroblasts and the formation of tumors after injection of NIH
      RET/PTC3 cells into nude mice. Thus, targeting RET oncogenes with ZD6474 might
      offer a potential treatment strategy for carcinomas sustaining oncogenic
      activation of RET.

PMID- 12499272
TI  - Inhibition of the mammalian target of rapamycin sensitizes U87 xenografts to
      fractionated radiation therapy.
AB  - The mammalian target of rapamycin (mTOR) modulates key signaling pathways that
      promote uncontrolled proliferation of glioblastoma multiforme (GBM). Because
      rapid tumor proliferation may contribute to the clinical radioresistance of GBM
      tumors, the combination of rapamycin, a selective mTOR inhibitor, and radiation
      was studied in vitro and in vivo in a GBM model. In monolayer cultures of U87 and
      SKMG-3 cells, rapamycin had no impact on radiation sensitivity. In contrast,
      rapamycin significantly enhanced the efficacy of fractionated radiation of
      established U87 xenografts in nude mice. Similar effects were seen in U87
      spheroids treated with rapamycin and radiation, which suggests that the
      sensitizing effects of this drug are dependent on disruption of mTOR signaling
      pathways specifically within tumor cells. Inhibition of these signaling pathways
      can lead to inhibition of G(1)-specific cyclin-dependent kinase activities, and
      this could contribute to the sensitizing effects of rapamycin. Consistent with
      this idea, roscovitine, a specific cyclin-dependent kinase inhibitor, also
      enhanced the efficacy of fractionated radiation in U87 spheroids. These data
      demonstrate that inhibition of tumor proliferation does not diminish the efficacy
      of fractionated radiation and suggest that disruption of key signal transduction
      pathways may significantly enhance the effectiveness of radiation therapy in
      malignant gliomas.

PMID- 12499273
TI  - Disruption of the murine major vault protein (MVP/LRP) gene does not induce
      hypersensitivity to cytostatics.
AB  - Vaults are ribonucleoprotein particles with a distinct structure and a high
      degree of conservation between species. Although no function has been assigned to
      the complex yet, there is some evidence for a role of vaults in multidrug
      resistance. To confirm a direct relation between vaults and multidrug resistance,
      and to investigate other possible functions of vaults, we have generated a major
      vault protein (MVP/lung resistance-related protein) knockout mouse model. The
      MVP(-/-) mice are viable, healthy, and show no obvious abnormalities. We
      investigated the sensitivity of MVP(-/-) embryonic stem cells and bone marrow
      cells derived from the MVP-deficient mice to various cytostatic agents with
      different mechanisms of action. Neither the MVP(-/-) embryonic stem cells nor the
      MVP(-/-) bone marrow cells showed an increased sensitivity to any of the drugs
      examined, as compared with wild-type cells. Furthermore, the activities of the
      ABC-transporters P-glycoprotein, multidrug resistance-associated protein and
      breast cancer resistance protein were unaltered on MVP deletion in these cells.
      In addition, MVP wild-type and deficient mice were treated with the anthracycline
      doxorubicin. Both groups of mice responded similarly to the doxorubicin
      treatment. Our results suggest that MVP/vaults are not directly involved in the
      resistance to cytostatic agents.

PMID- 12499274
TI  - Gadd45a protects against UV irradiation-induced skin tumors, and promotes
      apoptosis and stress signaling via MAPK and p53.
AB  - Skin cancer is the most frequent form of malignancy in the world, and UV
      radiation is the primary environmental carcinogen responsible for its
      development. Herein we demonstrate that Gadd45a is a critical factor protecting
      the epidermis against UV radiation-induced tumorigenesis by promoting damaged
      keratinocytes to undergo apoptosis and/or cell cycle arrest, two crucial events
      that prevent the expansion of mutant or deregulated cells. Whereas Gadd45a has
      been implicated in cell cycle arrest, apoptosis, and DNA repair, to determine the
      physiological function of endogenous Gadd45a after genotoxic stress, the skin of
      Gadd45a-null mice was targeted with UV radiation. We report that Gadd45a induces
      apoptosis and cell cycle arrest by maintaining p38 and c-JNK MAPK activation in
      keratinocytes. The absence of Gadd45a results in loss of sustained p38/JNK MAPK
      activity beyond 15-30 min after UV radiation that leads to inadequate p53
      activation and loss of normal activation of G(1) and G(2) checkpoints. Moreover,
      loss of Gadd45a dramatically reduces UV-induced apoptotic keratinocytes, "sunburn
      cells." Consequently, Gadd45a-null mice are more prone to tumors relative to wild
      type mice. Therefore, we conclude that Gadd45a, like p53, is a key component
      protecting skin against UV-induced tumors.

PMID- 12499275
TI  - Tissue-specific induction of p53 targets in vivo.
AB  - The in vivo response to radiotherapy is not well understood but appears to
      involve the p53 tumor suppressor protein. We investigated the expression of
      apoptosis-inducing p53 target genes during gamma-irradiation-induced cell death
      in p53(+/+) or p53(-/-) mouse tissues using in situ hybridization. Our results
      reveal striking tissue specificity with distinct regulation of target p53-induced
      genes in different cells and tissue compartments, as well as variations in
      dependence on p53 for basal expression. p53-dependent induction of Puma occurred
      in the splenic white pulp, whereas Noxa and Bid were induced in the red pulp.
      These patterns correlated with activation of caspase-3 in both compartments. All
      apoptotic targets of p53 studied here (DR5, Bid, Puma, Noxa) were induced in the
      jejunum and ileum, which appeared to be the tissues most sensitive to
      irradiation. We also observed unexpected differences in p53 target gene
      activation between the transverse and descending colon. Finally, in the liver
      where irradiation did not lead to caspase-3 activation, we primarily observed
      p21(WAF1) induction as the major p53-dependent target gene response. Our findings
      indicate that the selectivity of p53 in transactivation following DNA damage in
      vivo results in unique tissue and cell type specificity, which may correlate with
      growth arrest or variable sensitivity to gamma-irradiation.

PMID- 12499276
TI  - Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic
      potential of murine B16 melanoma cells.
AB  - The chemokine receptors CC chemokine receptor (CCR) 7 and CXC chemokine receptor
      (CXCR) 4 have been implicated in cancer metastasis. To evaluate whether CXCR4 is
      sufficient to increase tumor metastasis in an organ-specific manner, we
      transduced murine B16 melanoma cells with CXCR4 (CXCR4-B16) and followed the
      metastatic fate of the transduced cells in both i.v. and s.c. inoculation models
      of metastasis. CXCR4-B16 cells demonstrated marked increases (>10-fold) in
      pulmonary metastasis compared with vector (pLNCX2)-B16 after i.v. and s.c.
      inoculation of tumor cells. The increase in metastasis could be completely
      inhibited by T22, a small peptide antagonist of CXCR4. As early as 24 and 48 h
      after i.v. injection, CXCR4-B16 cells were significantly increased in the lung
      compared with control B16 cells by 5- and 10-fold (P < 0.05), respectively. CXCR4
      B16 cells adhered better to both dermal and pulmonary microvascular endothelial
      cells relative to control B16 cells. Moreover, CXCL12 promoted the growth of
      CXCR4-B16 cells in vitro. Whereas expression of CXCR4 in B16 cells dramatically
      enhanced pulmonary metastasis, metastasis to the lymph nodes, liver, and kidney
      was rare. Immunohistochemical staining of both primary human cutaneous melanoma
      and pulmonary metastases revealed CXCR4 expression. Thus, CXCR4 plays a
      potentially important role in promoting organ-selective metastasis, possibly by
      stimulating tumor adhesion to microvascular endothelial cells and by enhancing
      the growth of tumor cells under stress.

PMID- 12499277
TI  - Constitutive activation of Akt/protein kinase B in melanoma leads to up
      regulation of nuclear factor-kappaB and tumor progression.
AB  - The serine/threonine kinase Akt/protein kinase B and the pleiotropic
      transcription factor nuclear factor-kappaB [NF-kappaB (p50/p65)] play important
      roles in the control of cell proliferation, apoptosis, and oncogenesis. Previous
      studies from our laboratory have shown the constitutive activation of NF-kappaB
      in melanoma cells. However, the mechanism of this activation is not clearly
      understood. The purpose of this study was to explore the role of Akt in the
      activation of NF-kappaB during melanoma tumor progression. Based on our
      observation that two of the five melanoma cell lines examined exhibit
      constitutive Akt activation, we evaluated Akt activation by immunohistochemistry
      in a series of pigmented skin lesions using an antibody specific for phospho-Akt
      Ser-473. Normal and slightly dysplastic nevi exhibited no significant Akt
      expression, in marked contrast to the dramatic Akt immunoreactivity seen in
      severely dysplastic nevi and melanomas (66.3% positive). When these same lesions
      were stained for nuclear p65, a similar expression pattern was observed. In
      addition, interruption of Akt activation resulted in increased apoptosis and
      decreased NF-kappaB promoter activity. These results indicate that activation of
      Akt kinase is linked to enhanced NF-kappaB nuclear localization and
      transactivation. We propose that activation of Akt may be an early marker for
      tumor progression in melanoma.

PMID- 12499278
TI  - Simultaneous reduction in cancer pain, bone destruction, and tumor growth by
      selective inhibition of cyclooxygenase-2.
AB  - More than half of all chronic cancer pain arises from metastases to bone, and
      bone cancer pain is one of the most difficult of all persistent pain states to
      fully control. Several tumor types including sarcomas and breast, prostate, and
      lung carcinomas grow in or preferentially metastasize to the skeleton where they
      proliferate, and induce significant bone remodeling, bone destruction, and cancer
      pain. Many of these tumors express the isoenzyme cycloxygenase-2 (COX-2), which
      is involved in the synthesis of prostaglandins. To begin to define the role COX-2
      plays in driving bone cancer pain, we used an in vivo model where murine
      osteolytic 2472 sarcoma cells were injected and confined to the intramedullary
      space of the femur in male C3HHeJ mice. After tumor implantation, mice develop
      ongoing and movement-evoked bone cancer pain-related behaviors, extensive tumor
      induced bone resorption, infiltration of the marrow space by tumor cells, and
      stereotypic neurochemical alterations in the spinal cord reflective of a
      persistent pain state. Thus, after injection of tumor cells, bone destruction is
      first evident at day 6, and pain-related behaviors are maximal at day 14. A
      selective COX-2 inhibitor was administered either acutely [NS398; 100 mg/kg,
      i.p.] on day 14 or chronically in chow [MF. tricyclic; 0.015%, p.o.] from day 6
      to day 14 after tumor implantation. Acute administration of a selective COX-2
      inhibitor attenuated both ongoing and movement-evoked bone cancer pain, whereas
      chronic inhibition of COX-2 significantly reduced ongoing and movement-evoked
      pain behaviors, and reduced tumor burden, osteoclastogenesis, and bone
      destruction by >50%. The present results suggest that chronic administration of a
      COX-2 inhibitor blocks prostaglandin synthesis at multiple sites, and may have
      significant clinical utility in the management of bone cancer and bone cancer
      pain.

PMID- 12499279
TI  - Impact of epidermal growth factor receptor expression on survival and pattern of
      relapse in patients with advanced head and neck carcinoma.
AB  - A correlative study was performed to address the impact of epidermal growth
      factor receptor (EGFR) overexpression on survival and pattern of failure in
      patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled
      in a Phase III trial and randomized to receive conventional radiotherapy. The
      study population comprised 155 of 268 (58%) randomized patients with sufficient
      pretreatment biopsy specimens for immunohistochemical assay. The specimens were
      dewaxed and incubated after standard preparation with mouse monoclonal antibodies
      recognizing the extracellular domain of the EGFR molecule. The catalyzed product
      was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly
      counterstained with Mayer's hematoxylin. Quantitative EGFR immunohistochemistry
      (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of
      the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and
      quick score (QS). These EGFR IHC parameters were correlated with the T stage, N
      stage, combined stage grouping, and recursive partitioning analysis classes.
      Subsequently, the EGFR parameters were correlated with the outcome end points,
      i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR)
      relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide
      variation in EGFR expression (MOD, 0.2-66.0; SI, 0.3-97.0; QS, 0.01-69.9) with a
      relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There
      was no correlation between EGFR expression and T stage, N stage, stage grouping,
      and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS
      rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly
      significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse
      rate was highly significantly higher (P = 0.0031) compared with those of patients
      with low EGFR-expressing HNSCCs. However, there was no difference in the distant
      metastasis rate between the two groups (P = 0.96). Significant correlations,
      although somewhat less robust than MOD, were also observed between SI and QS and
      the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR
      expression was an independent determinant of survival and a robust independent
      predictor of LR relapse. In summary, this correlative study in a large series of
      patients revealed that EGFR expression, which varied considerably among HNSCCs,
      was a strong independent prognostic indicator for OS and DFS and a robust
      predictor for LR relapse but not for distant metastasis. The data suggest that
      EGFR IHC should be considered for selecting patients for more aggressive combined
      therapies or enrollment into trials targeting EGFR signaling pathways.

PMID- 12499280
TI  - SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor
      angiogenesis.
AB  - Neuroblastoma (NB), a common pediatric neoplasm, consists of two main cell
      populations: neuroblastic/ganglionic cells and Schwann cells. NB tumors with
      abundant Schwannian stroma display a more benign clinical behavior than stroma
      poor tumors. Recent studies suggest that Schwann cells influence NB tumor growth
      via secreted factors that induce differentiation, suppress proliferation, and
      inhibit angiogenesis. Two angiogenesis inhibitors, pigment epithelium-derived
      factor and tissue inhibitor of metalloproteinase-2, have been detected in Schwann
      cell secretions. Here, we isolated another Schwann cell-derived secreted
      inhibitor of angiogenesis, a 43-kDa protein identified as SPARC (secreted protein
      acidic and rich in cysteine), an extracellular matrix protein. We found SPARC to
      be critical for the antiangiogenic phenotype of cultured Schwann cells. We also
      show that purified SPARC potently inhibits angiogenesis and significantly impairs
      NB tumor growth in vivo. SPARC may be an effective candidate for the treatment of
      children with clinically aggressive, Schwannian stroma-poor NB tumors.

PMID- 12499281
TI  - Chemoradiation of cervical cancer cells: targeting human papillomavirus E6 and
      p53 leads to either augmented or attenuated apoptosis depending on the platinum
      carrier ligand.
AB  - Recent clinical trials comparing concurrent chemotherapy and radiation with
      radiation alone in cervical cancer have shown that chemoradiation reduces the
      risk of death by 30-50%. Despite the clinical success, treatment responses at the
      cellular level are still inadequately explored. A key event in cervical
      carcinogenesis is the disruption of p53 tumor suppressor pathway by human
      papillomavirus (HPV) E6 oncogene. We found that regardless of the HPV type in
      SiHa (HPV 16+) CaSki (HPV 16+), HeLa (HPV 18+), and UT-DEC-1 (HPV 33+) cell
      lines, cisplatin, carboplatin, and a novel platinum compound, oxaliplatin,
      activated a p53 reporter and reduced the HPV E6 mRNA. Carboplatin and oxaliplatin
      treatment led also to stabilization of p53, whereas none of the platinums changed
      p73 levels. After irradiation (IR) alone, a decrease in HPV E6 mRNA levels and an
      activation of the p53-reporter were detected in SiHa, CaSki, and HeLa cells, but
      not in UT-DEC-1 cells. Concomitant platinum treatment and IR led to poly(ADP
      ribose) polymerase cleavage as a sign of caspase-3 activation and apoptosis.
      Clonogenic survival was enhanced by expressing a dominant negative p53 or ectopic
      HPV16 E6 in SiHa and HeLa cells treated with IR, carboplatin, or oxaliplatin or
      with a combination of IR + carboplatin or oxaliplatin. In contrast, dominant
      negative p53 or ectopic HPV 16 E6 sensitized the cells to cisplatin. Pt
      chemotherapeutics and radiation had a synergistic cytotoxic effect as determined
      by Bliss independence criterion. Taken together, p53 has a significant role in
      the cellular response to chemoradiation treatment in cervical cancer cell lines,
      but p53 activity may have a dramatically different effect on cell survival
      depending on the platinum carrier ligand.

PMID- 12499282
TI  - Insulin-like growth factor-I antagonizes the antiproliferative effects of
      cyclooxygenase-2 inhibitors on BxPC-3 pancreatic cancer cells.
AB  - Cyclooxygenase (COX)-2 inhibitors demonstrate modest antineoplastic activity in
      experimental models of human malignancies, but little is known about factors that
      may confer resistance to their antiproliferative actions. We observed that fetal
      bovine serum antagonizes growth inhibition and G(1) arrest induced by two COX-2
      inhibitors (NS-398 and celecoxib) on BxPC-3 pancreatic cancer cells. We
      investigated the hypothesis that insulin-like growth factor I (IGF-I), a major
      survival factor present in serum, mediates these effects. Treatment of BxPC-3
      cells with 25 micro M celecoxib in 1% fetal bovine serum-containing medium for 48
      h resulted in a approximately 40% decrease in cell viability. Coincubation of
      BxPC-3 cells with 25 micro M celecoxib and 50 ng/ml IGF-I resulted in complete
      attenuation of the celecoxib-associated decrease in cell viability. Cell cycle
      analysis revealed that this IGF-I-induced increase in cell viability was
      correlated with an IGF-I-induced inhibition of celecoxib-mediated G(1) arrest.
      Similar results were observed when another COX-2 inhibitor (50 micro M NS-398)
      was used. When IGF-binding protein-3 (an inhibitor of IGF-I bioactivity) was
      added in combination with 25 micro M celecoxib, enhanced growth inhibition was
      observed (approximately 60% decrease in cell viability). Treatment of BxPC-3
      cells with a higher dose (50 micro M) of celecoxib for 24 h resulted in the
      induction of apoptosis, as assayed by flow cytometry and poly(ADP-ribose)
      polymerase cleavage. Addition of 50 ng/ml IGF-I resulted in a complete
      attenuation of celecoxib-induced apoptosis. The protection from celecoxib-induced
      apoptosis by IGF-I correlated with an increase in the levels of the activated
      antiapoptotic protein Akt. These results suggest that alterations of IGF-I levels
      or IGF-I receptor signal transduction modulate the antineoplastic actions of COX
      2 inhibitors.

PMID- 12499286
TI  - Wavelets in bioinformatics and computational biology: state of art and
      perspectives.
AB  - MOTIVATION: At a recent meeting, the wavelet transform was depicted as a small
      child kicking back at its father, the Fourier transform. Wavelets are more
      efficient and faster than Fourier methods in capturing the essence of data.
      Nowadays there is a growing interest in using wavelets in the analysis of
      biological sequences and molecular biology-related signals. RESULTS: This review
      is intended to summarize the potential of state of the art wavelets, and in
      particular wavelet statistical methodology, in different areas of molecular
      biology: genome sequence, protein structure and microarray data analysis. I
      conclude by discussing the use of wavelets in modeling biological structures.

PMID- 12499287
TI  - Novel organelle-targeting signals in viral proteins.

PMID- 12499288
TI  - Reconstruction of DNA sequencing by hybridization.
AB  - MOTIVATION: It is widely recognized that the hybridization process is prone to
      errors and that the future of DNA sequencing by hybridization is predicated on
      the ability to successfully cope with such errors. However, the occurrence of
      hybridization errors results in the computational difficulty of the
      reconstruction of DNA sequencing by hybridization. The reconstruction problem of
      DNA sequencing by hybridization with errors is a strongly NP-hard problem. So far
      the problem has not been solved well. RESULTS: In this paper, a new approach is
      presented to solve the reconstruction problem of DNA sequencing by hybridization,
      which realizes the computational part of the SBH experiment. The proposed
      algorithm accepts both the negative and positive errors. The computational
      experiments show that the algorithm behaves satisfactorily, especially for the
      case with k-tuple repetitions and positive errors.

PMID- 12499289
TI  - A divide-and-conquer approach to fragment assembly.
AB  - MOTIVATION: One of the major problems in DNA sequencing is assembling the
      fragments obtained by shotgun sequencing. Most existing fragment assembly
      techniques follow the overlap-layout-consensus approach. This framework requires
      extensive computation in each phase and becomes inefficient with increasing
      number of fragments. RESULTS: We propose a new algorithm which solves the
      overlap, layout, and consensus phases simultaneously. The fragments are clustered
      with respect to their Average Mutual Information (AMI) profiles using the k-means
      algorithm. This removes the unnecessary burden of considering the collection of
      fragments as a whole. Instead, the orientation and overlap detection are solved
      efficiently, within the clusters. The algorithm has successfully reconstructed
      both artificial and real data. AVAILABILITY: Available on request from the
      authors.

PMID- 12499290
TI  - Representation of DNA sequences with virtual potentials and their processing by
      (SEQREP) Kohonen self-organizing maps.
AB  - MOTIVATION: We propose representing individual positions in DNA sequences by
      virtual potentials generated by other bases of the same sequence. This is a
      compact representation of the neighbourhood of a base. The distribution of the
      virtual potentials over the whole sequence can be used as a representation of the
      entire sequence (SEQREP code). It is a flexible code, with a length independent
      of the sequence size, does not require previous alignment, and is convenient for
      processing by neural networks or statistical techniques. RESULTS: To evaluate its
      biological significance, the SEQREP code was used for training Kohonen self
      organizing maps (SOMs) in two applications: (a) detection of Alu sequences, and
      (b) classification of sequences encoding for HIV-1 envelope glycoprotein (env)
      into subtypes A-G. It was demonstrated that SOMs clustered sequences belonging to
      different classes into distinct regions. For independent test sets, very high
      rates of correct predictions were obtained (97% in the first application, 91% in
      the second). Possible areas of application of SEQREP codes include functional
      genomics, phylogenetic analysis, detection of repetitions, database retrieval,
      and automatic alignment. AVAILABILITY: Software for representing sequences by
      SEQREP code, and for training Kohonen SOMs is made freely available from
      http://www.dq.fct.unl.pt/qoa/jas/seqrep. SUPPLEMENTARY INFORMATION: Supplementary
      material is available at http://www.dq.fct.unl.pt/qoa/jas/seqrep/bioinf2002

PMID- 12499291
TI  - Genetic algorithms applied to multi-class prediction for the analysis of gene
      expression data.
AB  - MOTIVATION: An important challenge in the use of large-scale gene expression data
      for biological classification occurs when the expression dataset being analyzed
      involves multiple classes. Key issues that need to be addressed under such
      circumstances are the efficient selection of good predictive gene groups from
      datasets that are inherently 'noisy', and the development of new methodologies
      that can enhance the successful classification of these complex datasets.
      METHODS: We have applied genetic algorithms (GAs) to the problem of multi-class
      prediction. A GA-based gene selection scheme is described that automatically
      determines the members of a predictive gene group, as well as the optimal group
      size, that maximizes classification success using a maximum likelihood (MLHD)
      classification method. RESULTS: The GA/MLHD-based approach achieves higher
      classification accuracies than other published predictive methods on the same
      multi-class test dataset. It also permits substantial feature reduction in
      classifier genesets without compromising predictive accuracy. We propose that GA
      based algorithms may represent a powerful new tool in the analysis and
      exploration of complex multi-class gene expression data. AVAILABILITY:
      Supplementary information, data sets and source codes are available at
      http://www.omniarray.com/bioinformatics/GA.

PMID- 12499292
TI  - Evolutionary algorithms for finding optimal gene sets in microarray prediction.
AB  - MOTIVATION: Microarray data has been shown recently to be efficacious in
      distinguishing closely related cell types that often appear in different forms of
      cancer, but is not yet practical clinically. However, the data might be used to
      construct a minimal set of marker genes that could then be used clinically by
      making antibody assays to diagnose a specific type of cancer. Here a replication
      algorithm is used for this purpose. It evolves an ensemble of predictors, all
      using different combinations of genes to generate a set of optimal predictors.
      RESULTS: We apply this method to the leukemia data of the Whitehead/MIT group
      that attempts to differentially diagnose two kinds of leukemia, and also to data
      of Khan et al. to distinguish four different kinds of childhood cancers. In the
      latter case we were able to reduce the number of genes needed from 96 to less
      than 15, while at the same time being able to classify all of their test data
      perfectly. We also apply this method to two other cases, Diffuse large B-cell
      lymphoma data (Shipp et al., 2002), and data of Ramaswamy et al. on multiclass
      diagnosis of 14 common tumor types. AVAILABILITY:
      http://stravinsky.ucsc.edu/josh/gesses/.

PMID- 12499293
TI  - Analysis of whole-genome microarray replicates using mixed models.
AB  - MOTIVATION: Microarray experiments are inherently noisy. Replication is the key
      to estimating realistic fold-changes despite such noise. In the analysis of the
      various sources of noise the dependency structure of the replication needs to be
      taken into account. RESULTS: We analyzed replicate data sets from a Mycobacterium
      tuberculosis trcS mutant in order to identify differentially expressed genes and
      suggest new methods for filtering and normalizing raw array data and for imputing
      missing values. Mixed ANOVA models are applied to quantify the various sources of
      error. Such analysis also allows us to determine the optimal number of samples
      and arrays. Significance values for differential expression are obtained by a
      hierarchical bootstrapping scheme on scaled residuals. Four highly upregulated
      genes, including bfrB, were analyzed further. We observed an artefact, where
      transcriptional readthrough from these genes led to apparent upregulation of
      adjacent genes. AVAILABILITY: All methods and data discussed are available in the
      package YASMAhttp://www.cryst.bbk.ac.uk/wernisch/yasma.html for the statistical
      data analysis system R (http://www.R-project.org).

PMID- 12499294
TI  - Prediction of biologically significant components from microarray data:
      Independently Consistent Expression Discriminator (ICED).
AB  - MOTIVATION: Class distinction is a supervised learning approach that has been
      successfully employed in the analysis of high-throughput gene expression data.
      Identification of a set of genes that predicts differential biological states
      allows for the development of basic and clinical scientific approaches to the
      diagnosis of disease. The Independent Consistent Expression Discriminator (ICED)
      was designed to provide a more biologically relevant search criterion during
      predictor selection by embracing the inherent variability of gene expression in
      any biological state. The four components of ICED include (i) normalization of
      raw data; (ii) assignment of weights to genes from both classes; (iii) counting
      of votes to determine optimal number of predictor genes for class distinction;
      (iv) calculation of prediction strengths for classification results. The search
      criteria employed by ICED is designed to identify not only genes that are
      consistently expressed at one level in one class and at a consistently different
      level in another class but identify genes that are variable in one class and
      consistent in another. The result is a novel approach to accurately select
      biologically relevant predictors of differential disease states from a small
      number of microarray samples. RESULTS: The data described herein utilized ICED to
      analyze the large AML/ALL training and test data set (Golub et al., 1999,
      Science, 286, 531-537) in addition to a smaller data set consisting of an animal
      model of the childhood neurodegenerative disorder, Batten disease, generated for
      this study. Both of the analyses presented herein have correctly predicted
      biologically relevant perturbations that can be used for disease classification,
      irrespective of sample size. Furthermore, the results have provided candidate
      proteins for future study in understanding the disease process and the
      identification of potential targets for therapeutic intervention.

PMID- 12499295
TI  - Simple rules underlying gene expression profiles of more than six subtypes of
      acute lymphoblastic leukemia (ALL) patients.
AB  - MOTIVATIONS AND RESULTS: For classifying gene expression profiles or other types
      of medical data, simple rules are preferable to non-linear distance or kernel
      functions. This is because rules may help us understand more about the
      application in addition to performing an accurate classification. In this paper,
      we discover novel rules that describe the gene expression profiles of more than
      six subtypes of acute lymphoblastic leukemia (ALL) patients. We also introduce a
      new classifier, named PCL, to make effective use of the rules. PCL is accurate
      and can handle multiple parallel classifications. We evaluate this method by
      classifying 327 heterogeneous ALL samples. Our test error rate is competitive to
      that of support vector machines, and it is 71% better than C4.5, 50% better than
      Naive Bayes, and 43% better than k-nearest neighbour. Experimental results on
      another independent data sets are also presented to show the strength of our
      method. AVAILABILITY: Under http://sdmc.lit.org.sg/GEDatasets/, click on
      Supplementary Information.

PMID- 12499296
TI  - Mining gene expression databases for association rules.
AB  - MOTIVATION: Global gene expression profiling, both at the transcript level and at
      the protein level, can be a valuable tool in the understanding of genes,
      biological networks, and cellular states. As larger and larger gene expression
      data sets become available, data mining techniques can be applied to identify
      patterns of interest in the data. Association rules, used widely in the area of
      market basket analysis, can be applied to the analysis of expression data as
      well. Association rules can reveal biologically relevant associations between
      different genes or between environmental effects and gene expression. An
      association rule has the form LHS --> RHS, where LHS and RHS are disjoint sets of
      items, the RHS set being likely to occur whenever the LHS set occurs. Items in
      gene expression data can include genes that are highly expressed or repressed, as
      well as relevant facts describing the cellular environment of the genes (e.g. the
      diagnosis of a tumor sample from which a profile was obtained). RESULTS: We
      demonstrate an algorithm for efficiently mining association rules from gene
      expression data, using the data set from Hughes et al. (2000, Cell, 102, 109-126)
      of 300 expression profiles for yeast. Using the algorithm, we find numerous rules
      in the data. A cursory analysis of some of these rules reveals numerous
      associations between certain genes, many of which make sense biologically, others
      suggesting new hypotheses that may warrant further investigation. In a data set
      derived from the yeast data set, but with the expression values for each
      transcript randomly shifted with respect to the experiments, no rules were found,
      indicating that most all of the rules mined from the actual data set are not
      likely to have occurred by chance. AVAILABILITY: An implementation of the
      algorithm using Microsoft SQL Server with Access 2000 is available at
      http://dot.ped.med.umich.edu:2000/pub/assoc_rules/assoc_rules.zip. Our results
      from mining the yeast data set are available at
      http://dot.ped.med.umich.edu:2000/pub/assoc_rules/yeast_results.zip.

PMID- 12499297
TI  - MADGE: scalable distributed data management software for cDNA microarrays.
AB  - MOTIVATION: The human genome project and the development of new high-throughput
      technologies have created unparalleled opportunities to study the mechanism of
      diseases, monitor the disease progression and evaluate effective therapies. Gene
      expression profiling is a critical tool to accomplish these goals. The use of
      nucleic acid microarrays to assess the gene expression of thousands of genes
      simultaneously has seen phenomenal growth over the past five years. Although
      commercial sources of microarrays exist, investigators wanting more flexibility
      in the genes represented on the array will turn to in-house production. The
      creation and use of cDNA microarrays is a complicated process that generates an
      enormous amount of information. Effective data management of this information is
      essential to efficiently access, analyze, troubleshoot and evaluate the
      microarray experiments. RESULTS: We have developed a distributable software
      package designed to track and store the various pieces of data generated by a
      cDNA microarray facility. This includes the clone collection storage data,
      annotation data, workflow queues, microarray data, data repositories, sample
      submission information, and project/investigator information. This application
      was designed using a 3-tier client server model. The data access layer (1st tier)
      contains the relational database system tuned to support a large number of
      transactions. The data services layer (2nd tier) is a distributed COM server with
      full database transaction support. The application layer (3rd tier) is an
      internet based user interface that contains both client and server side code for
      dynamic interactions with the user. AVAILABILITY: This software is freely
      available to academic institutions and non-profit organizations at
      http://www.genomics.mcg.edu/niddkbtc.

PMID- 12499298
TI  - Gene selection: a Bayesian variable selection approach.
AB  - Selection of significant genes via expression patterns is an important problem in
      microarray experiments. Owing to small sample size and the large number of
      variables (genes), the selection process can be unstable. This paper proposes a
      hierarchical Bayesian model for gene (variable) selection. We employ latent
      variables to specialize the model to a regression setting and uses a Bayesian
      mixture prior to perform the variable selection. We control the size of the model
      by assigning a prior distribution over the dimension (number of significant
      genes) of the model. The posterior distributions of the parameters are not in
      explicit form and we need to use a combination of truncated sampling and Markov
      Chain Monte Carlo (MCMC) based computation techniques to simulate the parameters
      from the posteriors. The Bayesian model is flexible enough to identify
      significant genes as well as to perform future predictions. The method is applied
      to cancer classification via cDNA microarrays where the genes BRCA1 and BRCA2 are
      associated with a hereditary disposition to breast cancer, and the method is used
      to identify a set of significant genes. The method is also applied successfully
      to the leukemia data. SUPPLEMENTARY INFORMATION:
      http://stat.tamu.edu/people/faculty/bmallick.html.

PMID- 12499299
TI  - Predicting HIV drug resistance with neural networks.
AB  - MOTIVATION: Drug resistance is a very important factor influencing the failure of
      current HIV therapies. The ability to predict the drug resistance of HIV protease
      mutants may be useful in developing more effective and longer lasting treatment
      regimens. METHODS: The HIV resistance is predicted to two current protease
      inhibitors, Indinavir and Saquinavir. The problem was approached from two
      perspectives. First, a predictor was constructed based on the structural features
      of the HIV protease-drug inhibitor complex. A particular structure was
      represented by its list of contacts between the inhibitor and the protease. Next,
      a classifier was constructed based on the sequence data of various drug resistant
      mutants. In both cases, self-organizing maps were first used to extract the
      important features and cluster the patterns in an unsupervised manner. This was
      followed by subsequent labelling based on the known patterns in the training set.
      RESULTS: The prediction performance of the classifiers was measured by cross
      validation. The classifier using the structure information correctly classified
      previously unseen mutants with an accuracy of between 60 and 70%. Several
      architectures were tested on the more abundant sequence data. The best single
      classifier provided an accuracy of 68% and a coverage of 69%. Multiple networks
      were then combined into various majority voting schemes. The best combination
      yielded an average of 85% coverage and 78% accuracy on previously unseen data.
      This is more than two times better than the 33% accuracy expected from a random
      classifier.

PMID- 12499300
TI  - Finding the common structure shared by two homologous RNAs.
AB  - MOTIVATION: CARNAC is a new method for pairwise folding of RNA sequences. The
      program takes into account local similarity, stem energy, and covariations to
      produce the common folding. It can handle all RNA types, and has also been
      adapted to align a new homologous sequence along a reference structured sequence.
      RESULTS: Using different data sets, we show that CARNAC provides a good partial
      prediction for a wide range of sequences (16S ssu rRNA, RNase P RNA, viruses)
      with only two sequences. In presence of a whole family of sequences, we also show
      that CARNAC can be used to detect whether the sequences actually share the same
      structure. AVAILABILITY: CARNAC is available at the
      URLhttp://www.lifl.fr/~perrique/rna/.

PMID- 12499301
TI  - Search for structural similarity in proteins.
AB  - MOTIVATION: The expanding protein sequence and structure databases await methods
      allowing rapid similarity search. Geometric parameters-dihedral angle between two
      sequential peptide bond planes (V) and radius of curvature (R) as they appear in
      pentapeptide fragments in polypeptide chains-are proposed for use in evaluating
      structural similarity in proteins (VeaR). The parabolic (empirical) function
      expressing the radius of curvature's dependence on the V-angle in model
      polypeptides is altered in real proteins in a form characteristic for a
      particular protein. This can be used as a criterion for judging similarity.
      RESULTS: A structural comparison of proteins representing a wide spectrum of
      structures was assessed versus sequence similarity analysis based on the genetic
      semihomology algorithm. The term 'consensus structure', analogous to 'consensus
      sequence', was introduced for the serpine family. AVAILABILITY: Semihom-sequence
      comparison freely available on request from J. Leluk. VeaR-structural comparison
      freely available on request from I. Roterman.

PMID- 12499302
TI  - Whole-proteome interaction mining.
AB  - MOTIVATION: A major post-genomic scientific and technological pursuit is to
      describe the functions performed by the proteins encoded by the genome. One
      strategy is to first identify the protein-protein interactions in a proteome,
      then determine pathways and overall structure relating these interactions, and
      finally to statistically infer functional roles of individual proteins. Although
      huge amounts of genomic data are at hand, current experimental protein
      interaction assays must overcome technical problems to scale-up for high
      throughput analysis. In the meantime, bioinformatics approaches may help bridge
      the information gap required for inference of protein function. In this paper, a
      previously described data mining approach to prediction of protein-protein
      interactions (Bock and Gough, 2001, Bioinformatics, 17, 455-460) is extended to
      interaction mining on a proteome-wide scale. An algorithm (the phylogenetic
      bootstrap) is introduced, which suggests traversal of a phenogram, interleaving
      rounds of computation and experiment, to develop a knowledge base of protein
      interactions in genetically-similar organisms. RESULTS: The interaction mining
      approach was demonstrated by building a learning system based on 1,039
      experimentally validated protein-protein interactions in the human gastric
      bacterium Helicobacter pylori. An estimate of the generalization performance of
      the classifier was derived from 10-fold cross-validation, which indicated
      expected upper bounds on precision of 80% and sensitivity of 69% when applied to
      related organisms. One such organism is the enteric pathogen Campylobacter
      jejuni, in which comprehensive machine learning prediction of all possible
      pairwise protein-protein interactions was performed. The resulting network of
      interactions shares an average protein connectivity characteristic in common with
      previous investigations reported in the literature, offering strong evidence
      supporting the biological feasibility of the hypothesized map. For inferences
      about complete proteomes in which the number of pairwise non-interactions is
      expected to be much larger than the number of actual interactions, we anticipate
      that the sensitivity will remain the same but precision may decrease. We present
      specific biological examples of two subnetworks of protein-protein interactions
      in C. jejuni resulting from the application of this approach, including elements
      of a two-component signal transduction systems for thermoregulation, and a
      ferritin uptake network.

PMID- 12499303
TI  - Protein structures and information extraction from biological texts: the PASTA
      system.
AB  - MOTIVATION: The rapid increase in volume of protein structure literature means
      useful information may be hidden or lost in the published literature and the
      process of finding relevant material, sometimes the rate-determining factor in
      new research, may be arduous and slow. RESULTS: We describe the Protein Active
      Site Template Acquisition (PASTA) system, which addresses these problems by
      performing automatic extraction of information relating to the roles of specific
      amino acid residues in protein molecules from online scientific articles and
      abstracts. Both the terminology recognition and extraction capabilities of the
      system have been extensively evaluated against manually annotated data and the
      results compare favourably with state-of-the-art results obtained in less
      challenging domains. PASTA is the first information extraction (IE) system
      developed for the protein structure domain and one of the most thoroughly
      evaluated IE system operating on biological scientific text to date.
      AVAILABILITY: PASTA makes its extraction results available via a browser-based
      front end: http://www.dcs.shef.ac.uk/nlp/pasta/. The evaluation resources
      (manually annotated corpora) are also available through the website:
      http://www.dcs.shef.ac.uk/nlp/pasta/results.html.

PMID- 12499304
TI  - Simulating complex traits influenced by genes with fuzzy-valued effects in
      pedigreed populations.
AB  - MOTIVATION: Methods involving fuzzy theory have been rarely applied to genetics.
      We present an open platform for experimentation with fuzzy numbers as a tool to
      represent imprecise phenotypes in genetic modeling. RESULTS: A C++ library for
      simulation of genetic information transmission is introduced. The study of
      genetic linkage was its first goal, though a design so general as possible has
      been meant. Fuzzy-valued phenotypes are handled by means of fuzzy numbers.
      AVAILABILITY: ftp://carleos.etsiig.uniovi.es/pub/falin
      ftp://fisher.ciencias.uniovi.es/pub/falin
      ftp://bellman.ciencias.uniovi.es/pub/falin Licensed under the GNU General Public
      License version 2 (see http://www.gnu.org/licenses/gpl.html).

PMID- 12499305
TI  - Genetic Power Calculator: design of linkage and association genetic mapping
      studies of complex traits.
AB  - SUMMARY: A website for performing power calculations for the design of linkage
      and association genetic mapping studies of complex traits. AVAILABILITY: The
      package is made available athttp://statgen.iop.kcl.ac.uk/gpc/.

PMID- 12499306
TI  - MAVG: locating non-overlapping maximum average segments in a given sequence.
AB  - SUMMARY: MAVG is a software tool for finding k non-overlapping maximum-average
      segments that are sufficiently long in a given sequence of real numbers, for any
      k > 0. It has applications in several areas of biomolecular sequence analysis
      including locating GC-rich regions and CpG islands in a genomic sequence, and
      annotating multiple sequence alignments. AVAILABILITY:
      http://iubio.bio.indiana.edu/soft/molbio/pattern/cpg_islands/.

PMID- 12499307
TI  - An integrated genetic data environment (GDE)-based LINUX interface for analysis
      of HIV-1 and other microbial sequences.
AB  - MOTIVATION: Sequence databases encode a wealth of information needed to develop
      improved vaccination and treatment strategies for the control of HIV and other
      important pathogens. To facilitate effective utilization of these datasets, we
      developed a user-friendly GDE-based LINUX interface that reduces input/output
      file formatting. DESIGN AND RESULTS: GDE was adapted to the Linux operating
      system, bioinformatics tools were integrated with microbe-specific databases, and
      up-to-date GDE menus were developed for several clinically important viral,
      bacterial and parasitic genomes. Each microbial interface was designed for local
      access and contains Genbank, BLAST-formatted and phylogenetic databases.
      AVAILABILITY: GDE-Linux is available for research purposes by direct application
      to the corresponding author. Application-specific menus and support files can be
      downloaded from (http://www.bioafrica.net).

PMID- 12499308
TI  - An extensible application for assembling annotation for genomic data.
AB  - SUMMARY: AnnBuilder is an R package for assembling genomic annotation data. The
      system currently provides parsers to process annotation data from LocusLink, Gene
      Ontology Consortium, and Human Gene Project and can be extended to new data
      sources via user defined parsers. AnnBuilder differs from other existing systems
      in that it provides users with unlimited ability to assemble data from user
      selected sources. The products of AnnBuilder are files in XML format that can be
      easily used by different systems. AVAILABILITY: (http://www.bioconductor.org).
      Open source.

PMID- 12499309
TI  - Microarray data assembler.
AB  - SUMMARY: Large volumes of microarray data are generated and deposited in public
      databases. Most of this data is in the form of tab-delimited text files or Excel
      spreadsheets. Combining data from several of these files to reanalyze these data
      sets is time consuming. Microarray Data Assembler is specifically designed to
      simplify this task. The program can list files and data sources, convert selected
      text files into Excel files and assemble data across multiple Excel worksheets
      and workbooks. This program thus makes data assembling easy, saves time and helps
      avoid manual error. AVAILABILITY: The program is freely available for non-profit
      use, via email request from the author, after signing a Material Transfer
      Agreement with Johns Hopkins University.

PMID- 12499310
TI  - XdomView: protein domain and exon position visualization.
AB  - SUMMARY: The relationship between intron distribution in the eukaryotic gene and
      protein structural elements is essential for understanding the origin and
      evolution of genes. XdomView is a web-based viewer mapping protein structural
      domains and intron positions in eukaryotic homologues to its tertiary structure.
      The association of sequence signals to 3D structure in XdomView provides a
      valuable visualization environment for eukaryotic gene organization, gene
      evolution, protein folding and protein structure classification. AVAILABILITY:
      Freely available from http://surya.bic.nus.edu.sg/xdom.

PMID- 12499311
TI  - InterPreTS: protein interaction prediction through tertiary structure.
AB  - SUMMARY: InterPreTS (Interaction Prediction through Tertiary Structure) is a web
      based version of our method for predicting protein-protein interactions (Aloy and
      Russell, 2002, PROC: Natl Acad. Sci. USA, 99, 5896-5901). Given a pair of query
      sequences, we first search for homologues in a database of interacting domains
      (DBID) of known three-dimensional complex structures. Pairs of sequences
      homologous to a known interacting pair are scored for how well they preserve the
      atomic contacts at the interaction interface. InterPreTS includes a useful
      interface for visualising molecular details of any predicted interaction.
      AVAILABILITY: http://www.russell.embl.de/interprets.

PMID- 12499312
TI  - ConSurf: identification of functional regions in proteins by surface-mapping of
      phylogenetic information.
AB  - We recently developed algorithmic tools for the identification of functionally
      important regions in proteins of known three dimensional structure by estimating
      the degree of conservation of the amino-acid sites among their close sequence
      homologues. Projecting the conservation grades onto the molecular surface of
      these proteins reveals patches of highly conserved (or occasionally highly
      variable) residues that are often of important biological function. We present a
      new web server, ConSurf, which automates these algorithmic tools. ConSurf may be
      used for high-throughput characterization of functional regions in proteins.
      AVAILABILITY: The ConSurf web server is available at:http://consurf.tau.ac.il.
      SUPPLEMENTARY INFORMATION: A set of examples is available at
      http://consurf.tau.ac.il under 'GALLERY'.

PMID- 12499313
TI  - ModView, visualization of multiple protein sequences and structures.
AB  - SUMMARY: We describe ModView, a web application for visualization of multiple
      protein sequences and structures. ModView integrates a multiple structure viewer,
      a multiple sequence alignment editor, and a database querying engine. It is
      possible to interactively manipulate hundreds of proteins, to visualize
      conservative and variable residues, active and binding sites, fragments, and
      domains in protein families, as well as to display large macromolecular complexes
      such as ribosomes or viruses. As a Netscape plug-in, ModView can be included in
      HTML pages along with text and figures, which makes it useful for teaching and
      presentations. ModView is also suitable as a graphical interface to various
      databases because it can be controlled through JavaScript commands and called
      from CGI scripts. AVAILABILITY: ModView is available at
      http://guitar.rockefeller.edu/modview.

PMID- 12499314
TI  - Detection of hydrogen-bond signature patterns in protein families.
AB  - SUMMARY: We have developed a WWW server, HBPRINT, for the identification of
      hydrogen-bond signature patterns in protein families from their structures. The
      server calculates (a) common hydrogen bonds between two structures (b) a hydrogen
      bond fingerprint in a set of structural neighbours and (c) details of conserved
      hydrogen bonds. The server also enables the visualization of the hydrogen bond
      network comprising the signature pattern. AVAILABILITY: HBPRINT and a tutorial
      are available from http://144.16.93.115/hb_page/index.html.

PMID- 12499315
TI  - We are fifty.

PMID- 12499316
TI  - Folate fortification: enough already?

PMID- 12499317
TI  - Does milk intake in childhood protect against later osteoporosis?

PMID- 12499318
TI  - Isotopic tracer techniques for studying the bioavailability and bioefficacy of
      dietary carotenoids, particularly beta-carotene, in humans: a review.
AB  - Vitamin A deficiency is a serious health problem in many developing countries.
      Provitamin A carotenoids in fruit and vegetables are the major source of vitamin
      A for a large proportion of the world's population. However, the contribution of
      plant foods is substantial only when both the consumption and provitamin A
      content of such food is high and, at the same time, the bioefficacy of the
      provitamin A is high. With respect to provitamin A carotenoids, the term
      bioefficacy is defined as the product of the fraction of the ingested amount that
      is absorbed (bioavailability) and the fraction of that which is converted to
      retinol in the body (bioconversion). Isotopic tracer techniques can meet the need
      for accurate and precise estimates of the bioavailability, bioconversion, and
      bioefficacy of dietary carotenoids in humans. Use of such techniques will enable
      proper evaluation of food-based approaches to eliminating vitamin A deficiency.
      In addition, the putative antioxidant capacities of carotenoids can be better
      understood if their bioavailability is known. Here, we discuss how tracer
      techniques can be applied to obtain reliable and representative data. A step-by
      step discussion of aspects related to these techniques is provided, including
      study design, choice of isotopic tracers, dosing regimen, collection of samples,
      chemical analysis of samples, and data analysis.

PMID- 12499319
TI  - Change in the prevalence of overweight and obesity among young Australians, 1969
      1997.
AB  - BACKGROUND: Effective public policy requires information on the prevalence of
      overweight and obesity. OBJECTIVE: We determined changes in the population
      prevalence of overweight and obesity among young Australians (aged 7-15 y) from
      1969 to 1985 to 1997. DESIGN: Data from 5 independent population surveys were
      analyzed: the Australian Youth Fitness Survey, 1969; the Australian Health and
      Fitness Survey, 1985; the South Australian Schools Fitness and Physical Activity
      Survey, 1997; the New South Wales Schools Fitness and Physical Activity Survey,
      1997; and the Health of Young Victorians Study, 1997. Measured body mass index
      was used as the index of adiposity, and recently published body mass index cutoff
      values were used to categorize each subject as nonoverweight, overweight, obese,
      or either overweight or obese. RESULTS: For 1985-1997, the population prevalence
      of overweight increased by 60-70%, obesity increased 2-4-fold, and the combined
      overweight and obesity categories doubled. The findings were consistent across
      data sets and between the sexes. For 1969-1985, there was no change in the
      prevalence of overweight or obesity among girls, but among boys the prevalence of
      overweight increased by 35%, the prevalence of obesity trebled, and the
      prevalence of overweight and obesity combined increased by 60%. CONCLUSIONS: The
      data show that in 1985-1997, the prevalence of overweight and obesity combined
      doubled and that of obesity trebled among young Australians, but the increase
      over the previous 16 y was far smaller. These results should increase our sense
      of urgency in identifying and implementing effective responses to this major
      threat to public health.

PMID- 12499320
TI  - Effects of supplementation with fish oil-derived n-3 fatty acids and gamma
      linolenic acid on circulating plasma lipids and fatty acid profiles in women.
AB  - BACKGROUND: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and gamma
      linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The
      effects of supplement mixtures of these fatty acids on plasma lipids and the
      fatty acid compositions of serum phospholipids have received little attention.
      OBJECTIVE: The objective was to determine the effects of different levels of GLA
      supplementation together with a constant intake of EPA plus DHA on the
      triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid
      patterns (eicosanoid precursors) of serum phospholipids. DESIGN: Thirty-one women
      were assigned to 1 of 4 groups, equalized on the basis of their fasting
      triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA
      (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2),
      or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum
      phospholipids were measured on days 0 and 28. RESULTS: Plasma triacylglycerol
      concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1,
      and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2
      group. Dihomo-gamma-linolenic acid increased significantly in serum phospholipids
      only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4
      groups. CONCLUSIONS: A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood
      lipid and fatty acid profiles in healthy women. On the basis of calculated PROCAM
      values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of
      myocardial infarction.

PMID- 12499321
TI  - Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects
      consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic
      diets.
AB  - BACKGROUND: Hypertriglyceridemia is associated with increased risk of
      cardiovascular disease. Until recently, the importance of hepatic de novo
      lipogenesis (DNL) in contributing to hypertriglyceridemia was difficult to assess
      because of methodologic limitations. OBJECTIVE: We evaluated the extent of the
      contribution by DNL to different conditions associated with hypertriglyceridemia.
      DESIGN: After 5 d of an isoenergetic high-fat, low-carbohydrate diet, fasting DNL
      was measured in normoinsulinemic (<or= 85 pmol/L) lean (n = 9) and obese (n = 6)
      and hyperinsulinemic (>or= 115 pmol/L) obese (n = 8) subjects. Fasting DNL was
      measured after a low-fat, high-carbohydrate diet in normoinsulinemic lean (n = 5)
      and hyperinsulinemic obese (n = 5) subjects. Mass isotopomer distribution
      analysis was used to measure the fraction of newly synthesized fatty acids in
      VLDL-triacylglycerol. RESULTS: With the high-fat, low-carbohydrate diet,
      hyperinsulinemic obese subjects had a 3.7-5.3-fold higher fractional DNL (8.5 +/-
      0.7%) than did normoinsulinemic lean (1.6 +/- 0.5%) or obese (2.3 +/- 0.3%)
      subjects. With the low-fat, high-carbohydrate diet, normoinsulinemic lean and
      hyperinsulinemic obese subjects had similarly high fractional DNL (13 +/- 5.1%
      and 12.8 +/- 1.4%, respectively). Compared with baseline, consumption of the high
      fat, low-carbohydrate diet did not affect triacylglycerol concentrations.
      However, after the low-fat, high-carbohydrate diet, triacylglycerols increased
      significantly and DNL was 5-6-fold higher than in normoinsulinemic subjects
      consuming a high-fat diet. The increase in triacylglycerol after the low-fat,
      high-carbohydrate diet was correlated with fractional DNL (P < 0.01), indicating
      that subjects with high DNL had the greatest increase in triacylglycerols.
      CONCLUSIONS: These results support the concept that both hyperinsulinemia and a
      low-fat diet increase DNL, and that DNL contributes to hypertriglyceridemia.

PMID- 12499322
TI  - Cholesterol precursors and plant sterols in children with food allergy.
AB  - BACKGROUND: The data on lipid metabolism in allergic children is limited.
      OBJECTIVE: We investigated lipid and sterol metabolism in young children whose
      diets were restricted because of food allergy. DESIGN: Children in group A [n =
      21; mean (+/- SD) age: 1.78 +/- 0.73 y] were allergic to fish, eggs, and either
      cow milk or cereals; those in group B (n = 31, aged 1.45 +/- 0.58 y) were
      allergic to fish, eggs, and both cow milk and cereals. Cholesterol precursor and
      plant sterol to cholesterol ratios (10(2) x micro mol/mmol cholesterol) and
      apolipoprotein E phenotype distributions were analyzed in 36 subjects. The
      control group for cholesterol precursor and plant sterol measurements consisted
      of 18 healthy age-matched children. RESULTS: The mean serum cholesterol
      concentration was 3.6 +/- 0.6 mmol/L, and HDL cholesterol was 1.03 +/- 0.3 mmol/L
      in group A. Corresponding values in group B were 3.4 +/- 0.7 and 1.09 +/- 0.2
      mmol/L. The daily cholesterol intake was low: 61.3 +/- 36.0 mg in group A and
      50.7 +/- 48.5 mg in group B. Cholesterol precursor plant sterol concentrations
      were significantly higher in allergic subjects than in control subjects.
      CONCLUSIONS: Allergic children with restricted diets have a low intake of
      cholesterol and relatively low serum cholesterol concentrations. Dietary intake
      of plant sterols was obviously increased because of supplementation with rapeseed
      oil, which is rich in plant sterols, leading to elevated plant sterol
      concentrations. Plant sterols may have inhibited cholesterol absorption, which in
      turn stimulated cholesterol synthesis in compensation, also explaining the
      increased precursor sterol ratios in serum in our subjects.

PMID- 12499323
TI  - Iron status in association with cardiovascular disease risk in 3 controlled
      feeding studies.
AB  - BACKGROUND: The role of body iron stores in free radical-induced peroxidation and
      cardiovascular disease risk has been debated, but controlled feeding studies
      using measurements of non-transferrin-bound iron (NTBI) and LDL oxidation have
      not been conducted. OBJECTIVE: We tested the hypothesis that NTBI and other
      measures of iron status do not affect oxidative susceptibility in healthy
      subjects with normal iron status. DESIGN: Plasma samples were analyzed from 77
      healthy men and women aged 20-65 y who participated in 3 controlled feeding
      studies in which the type and amount of dietary fat were controlled. Iron status
      and in vitro LDL oxidation were assessed at baseline and at the end of each
      feeding period (4-8 wk). RESULTS: No significant relations were found between any
      measure of iron status (ferritin: 83 +/- 8.9 micro g/L; iron: 20.9 +/- 5.4 micro
      mol/L; TIBC: 74.4 +/- 11.0 micro mol/L; NTBI: 0.184 +/- 0.15 micro mol/L) and the
      in vitro measures of LDL oxidation (total dienes: 485 +/- 55 micro mol/mg LDL
      protein; lag time: 51.7 +/- 15.9 min; and rate of oxidation: 25.4 +/- 6.8 micro
      mol dienes.min(-1).g LDL protein(-1)). Equal-iron peanut butter-based diets were
      associated with higher plasma iron in men (22.4 +/- 3.8 micro mol/L) than was the
      olive oil diet (17.7 +/- 4.5 micro mol/L) (P = 0.02), but this slight elevation
      did not alter LDL oxidation. CONCLUSIONS: Diet composition may affect plasma iron
      in men, but LDL oxidative susceptibility is unaffected by the subtle variation in
      iron status. Thus, the results do not support a relation between iron status and
      LDL oxidative susceptibility, a possible risk factor for cardiovascular disease.

PMID- 12499324
TI  - Thermolabile methylenetetrahydrofolate reductase, homocysteine, and
      cardiovascular disease risk: the European Concerted Action Project.
AB  - BACKGROUND: Homozygotes for the thermolabile mutation (TT genotype) of the
      methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme have elevated
      plasma concentrations of the cardiovascular disease risk factor homocysteine,
      particularly if folate depleted. OBJECTIVE: We examined the relations between
      thermolabile MTHFR, plasma homocysteine, plasma folate, and vascular disease
      risk. DESIGN: This was a case-control comparison in 711 vascular disease cases
      and 747 controls from 9 European countries. RESULTS: The TT genotype was
      associated with higher homocysteine and lower plasma folate than the CC and CT
      genotypes in both cases and controls and a nonsignificant increase in vascular
      disease risk (1.26; 95% CI: 0.88, 1.81; P = 0.20). The frequency of the TT
      genotype in cases was not significantly different from that in controls (12.8%
      compared with 10.8%). After adjustment for traditional risk factors, the TT
      genotype was associated with an odds ratio of 1.48 (1.0, 2.20) for risk of
      vascular disease. This risk was attenuated after further adjustment for
      homocysteine. In subgroups with homocysteine concentrations >or= 9 micro mol/L,
      risk tended to be higher in CC than in TT subjects. However, CC subjects were
      characterized by a higher prevalence of the conventional risk factors associated
      with both elevated plasma homocysteine and serum creatinine. After adjustment,
      the risk of vascular disease associated with each genotype was not significantly
      different. CONCLUSIONS: There was a strong graded association between
      homocysteine and vascular risk in all genotypes. MTHFR genotype is a key
      determinant of plasma total homocysteine concentrations. The initially
      nonsignificant risk estimate associated with the TT genotype was strengthened
      after adjustment for conventional cardiovascular disease risk factors but was
      attenuated after adjustment for plasma folate and total homocysteine. The modest
      risk increase conferred by the TT genotype is mediated mainly by increased total
      homocysteine and low plasma folate concentrations.

PMID- 12499325
TI  - Is percentage body fat differentially related to body mass index in Hispanic
      Americans, African Americans, and European Americans?
AB  - BACKGROUND: Limited research has been done to explore differences between ethnic
      groups, including Hispanic Americans (HAs), in the association between percentage
      body fat (PBF) and body mass index (BMI; in kg/m(2)); the numbers of HAs are
      increasing in the US population. OBJECTIVE: We investigated whether the relation
      between PBF and BMI in adult HAs differed from that of African Americans (AAs)
      and European Americans (EAs). DESIGN: We used a multiple regression model in
      which PBF measured with dual energy X-ray absorptiometry was predicted by the
      reciprocal of BMI (1/BMI; in m(2)/kg) in a sample of 487 men (n(EA) = 192, n(AA)
      = 148, and n(HA) = 147) and 933 women (n(EA) = 448, n(AA) = 304, and n(HA) =
      181). RESULTS: For men, our results showed no significant differences between HAs
      and EAs, AAs and EAs, or HAs and AAs in the slope of the line relating 1/BMI to
      PBF. In women, there were significant differences in PBF as predicted by BMI
      between HAs and EAs (P < 0.002) and AAs and HAs (P = 0.020), but not between AAs
      and EAs. When PBF was estimated on the basis of predicting equations, the trend
      of the predicted PBF value in women differed according to ethnic group and BMI
      category. At a BMI < 30, HAs tended to have more body fat than did EAs and AAs,
      and at a BMI > 35, EAs tended to have more body fat than did the other groups.
      CONCLUSIONS: Our results show that the relation between PBF and BMI in HA women
      differs from that of EA and AA women.

PMID- 12499326
TI  - Whole-body skeletal muscle mass: development and validation of total-body
      potassium prediction models.
AB  - BACKGROUND: A substantial proportion of total body potassium (TBK) in humans is
      found in skeletal muscle (SM), thus affording a means of predicting total-body SM
      from whole-body counter-measured (40)K. There are now > 30 whole-body counters
      worldwide that have large cross-sectional and longitudinal TBK databases.
      OBJECTIVE: We explored 2 SM prediction approaches, one based on the assumption
      that the ratio of TBK to SM is stable in healthy adults and the other on a
      multiple regression TBK-SM prediction equation. DESIGN: Healthy subjects aged
      >or= 20 y were recruited for body-composition evaluation. TBK and SM were
      measured by whole-body (40)K counting and multislice magnetic resonance imaging,
      respectively. A conceptual model with empirically derived data was developed to
      link TBK and adipose tissue-free SM as the ratio of TBK to SM. RESULTS: A total
      of 300 subjects (139 men and 161 women) of various ethnicities with a mean (+/-
      SD) body mass index (in kg/m(2)) of 25.1 +/- 5.4 met the study entry criteria.
      The mean conceptual model-derived TBK-SM ratio was 122 mmol/kg, which was
      comparable to the measurement-derived TBK-SM ratios in men and women (119.9 +/-
      6.7 and 118.7 +/- 8.4 mmol/kg, respectively), although the ratio tended to be
      lower in subjects aged >or= 70 y. A strong linear correlation was observed
      between TBK and SM (r = 0.98, P < 0.001), with sex, race, and age as small but
      significant prediction model covariates. CONCLUSIONS: Two different types of
      prediction models were developed that provide validated approaches for estimating
      SM mass from (40)K measurements by whole-body counting. These methods afford an
      opportunity to predict SM mass from TBK data collected in healthy adults.

PMID- 12499327
TI  - Effect of low-glycemic-index dietary advice on dietary quality and food choice in
      children with type 1 diabetes.
AB  - BACKGROUND: The practicality of diets with a low glycemic index (GI) is
      controversial. Theoretically, low-GI diets may limit food choice and increase
      dietary fat intake, but there is little objective evidence to support such a
      theory. OBJECTIVE: The objective was to determine the effect of low-GI dietary
      advice on dietary quality and food choice in children with diabetes. DESIGN:
      Children aged 8-13 y with type 1 diabetes (n = 104) were recruited to a
      prospective, randomized study comparing the effects of traditional carbohydrate
      exchange dietary advice (CHOx) with those of more flexible low-GI dietary advice
      (LowGI). We determined the effect on long-term macronutrient intake and food
      choice with the use of 3-d food diaries. RESULTS: There were no differences in
      reported macronutrient intakes during any of the recording periods. After 12 mo,
      intakes of dietary fat (33.5 +/- 5.6% and 34.2 +/- 6.7% of energy, P = 0.65),
      carbohydrate (48.8 +/- 5.4% and 48.6 +/- 6.5% of energy, P = 0.86), protein (17.6
      +/- 2.5% and 17.3 +/- 3.7% of energy, P = 0.61), total sugars, and fiber did not
      differ significantly between the CHOx and LowGI groups, respectively. The average
      number of different carbohydrate food choices per day also did not differ
      significantly. Subjects in the lowest-GI quartile consumed less carbohydrate as
      potato and white bread, but more carbohydrate as dairy-based foods and whole
      grain breads than did subjects in the highest-GI quartile. CONCLUSION: Children
      with diabetes who receive low-GI dietary advice do not report more limited food
      choices or a diet with worse macronutrient composition than do children who
      consume a traditional carbohydrate-exchange diet.

PMID- 12499328
TI  - Meals with similar energy densities but rich in protein, fat, carbohydrate, or
      alcohol have different effects on energy expenditure and substrate metabolism but
      not on appetite and energy intake.
AB  - BACKGROUND: It has been suggested that the satiating power of the 4
      macronutrients follows the oxidation hierarchy: alcohol > protein > carbohydrate
      > fat. However, the experimental evidence for this is still scarce. OBJECTIVE:
      The goal was to investigate the effects on appetite, energy intake and
      expenditure, and substrate metabolism of meals rich in 1 of the 4 macronutrients.
      DESIGN: Subjective appetite sensations, ad libitum food intake, energy
      expenditure, substrate metabolism, and hormone concentrations were measured for 5
      h after breakfast meals with similar energy density and fiber contents but rich
      in either protein (32% of energy), carbohydrate (65% of energy), fat (65% of
      energy), or alcohol (23% of energy). Subjects were normal-weight, healthy women
      (n = 9) and men (n = 10) studied in a crossover design. RESULTS: There were no
      significant differences in hunger or satiety sensations or in ad libitum energy
      intake after the 4 meals. Diet-induced thermogenesis was larger after the alcohol
      meal (by 27%; P < 0.01), whereas protein produced an intermediary response (17%;
      NS) compared with carbohydrate and fat (meal effect: P < 0.01). After the alcohol
      meal, fat oxidation and leptin concentrations were greatly suppressed (meal
      effects, P < 0.0001 and P < 0.05) and triacylglycerol concentrations were as high
      as after the fat meal. CONCLUSION: Intake of an alcohol-rich meal stimulates
      energy expenditure but suppresses fat oxidation and leptin more than do
      isoenergetically dense meals rich in protein, carbohydrate, or fat. Despite
      differences in substrate metabolism and hormone concentrations, satiety and ad
      libitum energy intake were not significantly different between meals. Our data,
      therefore, do not support the proposed relation between the macronutrient
      oxidation hierarchy and the satiety hierarchy.

PMID- 12499329
TI  - Lysine requirements of chronically undernourished adult Indian men, measured by a
      24-h indicator amino acid oxidation and balance technique.
AB  - BACKGROUND: In earlier studies with well-nourished subjects that used a 24-h
      indicator amino acid oxidation or balance approach, we concluded that the 1985
      FAO/WHO/UNU requirement for lysine (12 mg x kg(-1) x d(-1)) was inadequate for
      healthy South Asian subjects and proposed a tentative requirement of 30 mg x kg(
      1) x d(-1). OBJECTIVE: We assessed whether chronic undernutrition, with low
      habitual dietary protein and lysine intakes, leads to changed lysine
      requirements. DESIGN: Twenty-seven otherwise clinically healthy, chronically
      undernourished Indian men were studied during 2 randomly assigned 7-d diet
      periods supplying 12 and 30, 18 and 36, or 24 and 42 mg lysine x kg(-1) x d(-1),
      based on an L-amino acid diet. The subjects' leucine intake was 40 mg x kg(-1) x
      d(-1). At 1800 on day 6, a 24-h intravenous [(13)C]leucine tracer-infusion
      protocol was conducted to assess leucine oxidation and daily leucine balance at
      each test lysine intake. RESULTS: A breakpoint was not identified in the lysine
      intake-leucine oxidation or balance response over the range of intakes studied.
      Mixed-models linear regression analysis indicated a mean requirement of 44 mg
      lysine x kg(-1) x d(-1) (95% CI: 36, 63) for the lysine intake-leucine balance
      relation. CONCLUSIONS: The mean lysine requirement in chronically undernourished
      men is estimated to be higher than the value of 30 mg x kg(-1) x d(-1) proposed
      for well-nourished individuals. This may be related to body-composition
      differences. It also suggests that these subjects have not elicited a metabolic
      adaptation in response to their habitually low lysine intakes by substantially
      improving their efficiency of dietary lysine utilization.

PMID- 12499330
TI  - Meta-analysis of nitrogen balance studies for estimating protein requirements in
      healthy adults.
AB  - BACKGROUND: The most recent international dietary protein recommendations for
      healthy adults are those developed and proposed by the 1985 FAO/WHO/UNU Joint
      Expert Consultation. OBJECTIVE: The objective was to analyze available nitrogen
      balance data to establish new recommendations for the protein required by healthy
      adults. DESIGN: Data were gathered from published nitrogen balance studies that
      had as their primary objective either the estimation of basal or maintenance
      requirements or the testing of the adequacy of specific nitrogen intakes in
      healthy adults. These data were synthesized to characterize the distribution of
      individual protein requirements; the effects of climate of the study site, adult
      age, sex, and dietary protein source on individual requirements; and the midpoint
      of and the variability between the protein requirements of healthy persons.
      RESULTS: Data for 235 individual subjects, each studied at >or= 3 test protein
      intakes, were gathered from 19 studies. The median estimated average requirement
      (EAR) of nitrogen from these data was 105 mg N x kg(-1) x d(-1). Individual
      requirements were found to fit a log-normal distribution. The median EAR was
      estimated as the median of this distribution, 105 mg N x kg(-1) x d(-1), whereas
      the 97.5th percentile (the recommended dietary allowance; RDA) was estimated from
      the distribution of the log of the requirement (after correction of the total
      observed variability to remove within-individual variability) as 132 mg N x kg(
      1) x d(-1). No significant differences between the climate of the study site,
      adult age class, sex, or source of dietary protein were observed, although there
      was an indication that women might have a lower requirement than do men.
      CONCLUSION: This meta-analysis provides new recommendations for dietary reference
      values, ie, an EAR (median) and RDA (97.5th percentile) for healthy adults of 105
      and 132 mg N x kg(-1) x d(-1) (0.65 and 0.83 g good-quality protein x kg(-1) x d(
      1)), respectively.

PMID- 12499331
TI  - Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan
      and tyrosine ratios.
AB  - BACKGROUND: The delivery of circulating tryptophan to the brain and its
      conversion to serotonin vary directly with plasma concentrations of tryptophan
      and inversely with those of other large neutral amino acids (LNAAs). Although
      carbohydrate-rich, protein-free formula diets have been shown to elevate, and
      high-protein diets to depress, the tryptophan-LNAA ratio, few data are available
      about this ratio's responses to actual meals. OBJECTIVE: We determined whether
      carbohydrate-rich or protein-rich breakfasts, such as those Americans normally
      eat, produce substantial differences in the plasma tryptophan-LNAA ratio and in
      the corresponding ratio for tyrosine, the precursor of brain dopamine and
      norepinephrine. DESIGN: Nine overnight-fasted subjects consumed, 3-7 d apart, a
      carbohydrate-rich (69.9 g carbohydrate and 5.2 g protein) and a protein-rich
      (15.4 g carbohydrate and 46.8 g protein) breakfast. Blood samples collected at
      baseline and after 40, 80, 120, and 240 min were assayed for tryptophan,
      tyrosine, the 5 other LNAAs, and insulin. RESULTS: The carbohydrate-rich and
      protein-rich breakfasts had significantly different effects on both the plasma
      tryptophan-LNAA and tyrosine-LNAA ratios (each P < 0.01). Among the 8 subjects
      who consumed both breakfasts, the median difference for tryptophan:LNAA was 54%
      (range: 36-88%) and for tyrosine:LNAA was 28% (range: 10-64%). Insulin
      concentrations rose significantly after the carbohydrate but not after the
      protein meal. CONCLUSIONS: High-carbohydrate and high-protein breakfasts similar
      to those Americans normally eat can cause substantial differences in the plasma
      tryptophan ratio and thus, probably, in brain tryptophan concentrations and
      serotonin synthesis. Such meals also change the plasma tyrosine ratio and may
      thereby modify catecholamine synthesis.

PMID- 12499332
TI  - Serum lycopene concentrations and carotid atherosclerosis: the Kuopio Ischaemic
      Heart Disease Risk Factor Study.
AB  - BACKGROUND: Interest in lycopene is growing rapidly following the recent
      publication of epidemiologic studies in which high circulating lycopene
      concentrations were associated with reductions in cardiovascular disease.
      Lycopene is one of the major carotenoids in the Western diet and is probably one
      of the protective factors in a vegetable-rich diet. OBJECTIVE: We studied the
      hypothesis that the intima-media thickness of the common carotid artery (CCA-IMT)
      would be greater in men with low serum lycopene concentrations. DESIGN: We
      investigated the relation between serum lycopene concentration and CCA-IMT in
      1028 middle-aged men (aged 46-64 y) in eastern Finland who were participants in
      the Kuopio Ischaemic Heart Disease Risk Factor study and who were examined in
      1991-1993. The subjects were classified into quarters according to serum lycopene
      concentration. RESULTS: In a covariance analysis with adjustment for covariates,
      the men in the lowest quarter of serum lycopene concentration had a significantly
      higher mean CCA-IMT and maximal CCA-IMT (P = 0.005 and P = 0.001 for the
      difference, respectively) than did the other men. The mean and maximal CCA-IMT
      increased linearly across the quarters of serum lycopene concentration.
      CONCLUSIONS: A low serum lycopene concentration is associated with a higher CCA
      IMT in middle-aged men from eastern Finland. This finding suggests that the serum
      lycopene concentration may play a role in the early stages of atherosclerosis.
      Increased thickness of the intima-media has been shown to predict coronary
      events; thus, lycopene intakes and serum concentrations may have clinical and
      public health relevance.

PMID- 12499333
TI  - Effect of dietary antioxidants on postprandial endothelial dysfunction induced by
      a high-fat meal in healthy subjects.
AB  - BACKGROUND: Persons following current dietary guidelines have a lower risk of
      mortality from coronary heart disease. OBJECTIVE: The objective was to compare
      the short-term effect of a high-fat meal and a high-carbohydrate meal, with and
      without dietary antioxidants, on vasomotor, antiplatelet, and hemostatic
      functions of the endothelium in healthy subjects. DESIGN: In an observer-blinded,
      randomized crossover study, 25 (13 men and 12 women) healthy subjects were given
      each of 3 meals in random order at 1-wk intervals: a high-fat meal (760 kcal), an
      isoenergetic high-carbohydrate meal, and a high-fat meal with dietary
      antioxidants from vegetables (865 kcal). Endothelial functions, as assessed by
      hemodynamic and rheologic responses to L-arginine--the natural precursor of
      nitric oxide--were evaluated before and 4 h after each meal. RESULTS: Unlike the
      high-carbohydrate meal, the high-fat meal increased the plasma concentrations of
      triacylglycerol (P < 0.01); both meals activated hemostasis. The high
      carbohydrate meal did not modify blood pressure, and platelet aggregation
      decreased in response to the L-arginine load (-7.1 +/- 2.3 mm Hg and -8.5 +/-
      4.5%, respectively). After the high-fat meal, the decrease in blood pressure in
      response to L-arginine was reduced (-1 +/- 0.8 mm Hg), and platelet aggregation
      showed a paradoxical increase (4.1 +/- 2.1%; P < 0.01 compared with the high
      carbohydrate meal). The high-fat meal with antioxidants partially restored the
      vascular response to L-arginine. CONCLUSION: Compared with a high-carbohydrate
      meal, a high-fat meal can modify endothelial functions toward a more
      atherogenetic profile, which is partially prevented by dietary antioxidants.

PMID- 12499334
TI  - No enhancing effect of vitamin A on iron absorption in humans.
AB  - BACKGROUND: Vitamin A and beta-carotene were recently reported to enhance iron
      absorption by counteracting the inhibitory effect of phytic acid in cereal-based
      meals and of polyphenol-containing beverages on nonheme-iron absorption in
      humans. OBJECTIVE: Our objective was to further evaluate the influence of vitamin
      A on iron absorption. DESIGN: Iron absorption from corn bread with or without
      added vitamin A (retinyl palmitate) was determined in 5 studies in young adult
      human subjects by using either a stable-isotope method (2 studies) or a
      radioisotope technique (3 studies). Iron absorption was measured by erythrocyte
      incorporation of the isotopic labels and by whole-body retention of (59)Fe. Corn
      bread was served with water (studies 1 and 3) or coffee (studies 2, 4, and 5).
      The studies differed in the amounts and chemical forms of added tracer and
      fortification iron. The possibility of methodologic artifacts in earlier
      investigations was evaluated. RESULTS: No effect of vitamin A on iron absorption
      from the test meals was identified in the individual studies by using paired
      Student's t test. A slightly negative effect of vitamin A on iron absorption was
      found with the use of analysis of variance. CONCLUSIONS: The previously reported
      findings of a positive effect of vitamin A on nonheme-iron absorption in humans
      was not confirmed. Incomplete isotopic equilibration of the tracer with native
      iron in the meal or with fortification iron cannot explain the previous findings.
      However, the present study does not exclude the possibility that suboptimal
      vitamin A status influences the effect of dietary vitamin A on iron absorption.

PMID- 12499336
TI  - Smoking and exposure to environmental tobacco smoke decrease some plasma
      antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary
      antioxidant intakes.
AB  - BACKGROUND: Free radicals in cigarette smoke may cause oxidative damage to
      macromolecules, contributing to cardiovascular diseases and cancer. Decreased
      plasma antioxidant concentrations may indicate cigarette smoke-related oxidative
      stress. OBJECTIVE: We compared the effects on plasma antioxidant concentrations
      in cotinine-confirmed active and passive smokers with those in nonsmokers,
      independent of differences in dietary intakes and other covariates. DESIGN:
      Plasma samples from 83 smokers, 40 passive smokers, and 36 nonsmokers were
      analyzed for total ascorbic acid, alpha- and gamma-tocopherols, 5 carotenoids,
      retinol, and cotinine. Groups were compared by using analysis of variance with
      adjustment for sex, age, race, body mass index, alcohol intake, triacylglycerol
      concentration, fruit and vegetable intakes, and dietary antioxidants. RESULTS:
      After adjustment for dietary antioxidant intakes and other covariates, smokers
      and passive smokers had significantly lower plasma beta-carotene concentrations
      than did nonsmokers (0.15, 0.17, and 0.24 micro mol/L, respectively) and
      significantly higher gamma-tocopherol concentrations (7.8, 7.8, and 6.5 micro
      mol/L, respectively). Smokers had significantly lower plasma ascorbic acid and
      beta-cryptoxanthin concentrations than did nonsmokers and passive smokers
      (ascorbic acid: 43.6, 54.5, and 54.6 micro mol/L, respectively; beta
      cryptoxanthin: 0.12, 0.16, and 0.16 micro mol/L, respectively) and significantly
      lower concentrations of lutein and zeaxanthin than did nonsmokers (0.33 compared
      with 0.41 micro mol/L). The P values for all the differences described above were
      < 0.05. No significant differences in plasma concentrations of alpha-tocopherol,
      alpha-carotene, total carotenoids, lycopene, or retinol were observed.
      CONCLUSIONS: These results indicate that cigarette smokers and nonsmokers exposed
      to cigarette smoke have a significantly lower plasma antioxidant status than do
      unexposed nonsmokers, independent of differences in dietary antioxidant intakes.
      Further research is required to explain why plasma gamma-tocopherol
      concentrations were significantly higher in smokers and passive smokers than in
      nonsmokers.

PMID- 12499335
TI  - Improved antioxidant and fatty acid status of patients with cystic fibrosis after
      antioxidant supplementation is linked to improved lung function.
AB  - BACKGROUND: Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8
      iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic
      fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to
      oxidative stress after respiratory exacerbations. OBJECTIVE: We examined changes
      in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status,
      and clinical markers resulting from short-term antioxidant supplementation.
      DESIGN: Forty-six CF patients were randomly assigned to either group A [low dose
      of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose
      of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro
      g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha),
      vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid
      composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide
      dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were
      measured before and after 8 wk of supplementation. RESULTS: Antioxidant defenses
      in group B improved, whereas those in group A did not: in groups B and A, the
      mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9
      micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and
      -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51
      +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and
      (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g
      hemoglobin, respectively (P = 0.016). There were no significant differences
      between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty
      acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or
      (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with
      (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005),
      (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in
      1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations
      correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583,
      P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010). CONCLUSIONS:
      Whereas increased beta-carotene, selenium, and fatty acid concentrations are
      linked to improved lung function, increased plasma fatty acid concentrations are
      linked to oxidative stress. If oxidative stress is deemed to be important to the
      clinical outcome of CF patients, means of reducing oxidative stress while
      maintaining a high-fat, high-energy diet must be investigated.

PMID- 12499337
TI  - Influence of environmental tobacco smoke on vitamin C status in children.
AB  - BACKGROUND: It is known that vitamin C status is compromised in smokers. The
      vitamin C status of nonsmokers who are exposed to environmental tobacco smoke
      (ETS) is now being elucidated. OBJECTIVE: We assessed vitamin C status in
      children who were either exposed or not exposed to ETS, and we sought to
      associate changes in vitamin C status with the amount of ETS exposure. DESIGN:
      The study group included 512 children aged 2-12 y; 50% of them were exposed to
      ETS in the home because their parents smoked. Dietary intake of vitamin C,
      obtained with a 24-h recall questionnaire, and blood ascorbate concentrations
      were compared in the exposed and unexposed groups. Smoke exposure was assessed by
      measuring a biomarker, urinary cotinine. Age, sex, and body mass index were
      examined as potential correlates of vitamin C status in each exposure category.
      RESULTS: Plasma ascorbate concentrations were lower, by 3.2 micro mol/L on
      average, in ETS-exposed children than in unexposed children who consumed
      equivalent amounts of vitamin C; this was a highly significant difference (P =
      0.002). This reduction in plasma ascorbate occurred even with very low exposure
      to ETS. CONCLUSIONS: ETS can reduce concentrations of ascorbate, an important
      blood antioxidant, even when the amount of smoke exposure is minimal. Children
      exposed to ETS should be encouraged to consume increased amounts of foods rich in
      vitamin C or should be given the equivalent amount of this vitamin as a
      supplement.

PMID- 12499338
TI  - Nonheme-iron absorption from a phytate-rich meal is increased by the addition of
      small amounts of pork meat.
AB  - BACKGROUND: Muscle tissue from various sources is known to promote nonheme-iron
      absorption. However, systematic studies of the dose dependency of this effect of
      meat on iron absorption from an inhibitory meal with low amounts of meat are
      lacking. OBJECTIVE: We investigated the dose-response effect of small amounts of
      meat on nonheme-iron absorption from a meal presumed to have low iron
      bioavailability. DESIGN: Forty-five healthy women with a mean (+/-SD) age of 24
      +/- 3 y were randomly assigned to 1 of 3 groups, each of which was served (A) a
      basic meal (rice, tomato sauce, pea puree, and a wheat roll) and (B) the basic
      meal with either 25, 50, or 75 g pork (longissimus muscle). Meal A contained 2.3
      mg nonheme iron, 7.4 mg vitamin C, and 220 mg (358 micro mol) phytate. Each meal
      was served twice, and the order of the meals was ABBA or BAAB. The meals were
      extrinsically labeled with (55)Fe or (59)Fe. Iron absorption was determined from
      measurements of (59)Fe whole-body retention and the activity of (55)Fe and (59)Fe
      in blood samples. RESULTS: Twenty-five grams meat did not increase nonheme-iron
      absorption significantly (P = 0.13), whereas absorption increased 44% (P < 0.001)
      and 57% (P < 0.001), respectively, when 50 and 75 g meat were added to the basic
      meal. In absolute values, this corresponds to an absorption that was 2.6% and
      3.4% higher, respectively, than that with the basic meal after adjustment of the
      data to a level of 40% absorption from a reference dose. CONCLUSION: Small
      amounts of meat (>or=50 g) significantly increase nonheme-iron absorption from a
      phytate-rich meal low in vitamin C.

PMID- 12499339
TI  - Women with low iron stores absorb iron from soybeans.
AB  - BACKGROUND: Worldwide, 30% of the population, a greater proportion of whom are
      women and children, is iron deficient. Soybeans are a major source of nonheme
      iron in many human diets, but information on iron bioavailability is still
      conflicting. Because much of soybean iron is in ferritin [distinct from the
      poorly bioavailable iron in cereals resulting from interactions between calcium,
      Fe(III), phytate, and proteins in the meal], soybeans provide a target for
      manipulating seed iron composition to achieve increased iron bioavailability.
      OBJECTIVE: The aim was to reevaluate soybean iron bioavailability. DESIGN:
      Eighteen women, most with marginal iron deficiency, consumed meals with
      intrinsically labeled ((55)Fe) soybeans (hydroponically grown and nonnodulating)
      as soup (n = 11) or muffins (n = 7) and a reference dose of (59)Fe as ferrous
      sulfate in ascorbate solution. The radioactivity in red cells was measured 14 and
      28 d later. RESULTS: The mean (55)Fe absorption from either soup or muffins was
      27% and that from the reference dose was 61%. (55)Fe was distributed
      approximately equally between protein (49.3 +/- 3.0%) and phytate, a contrast
      with nodulating soybeans likely caused by a high phosphate content in the growth
      medium. There was an expected inverse correlation (r = -0.793, P < 0.001) between
      red cell radioactivity and serum ferritin concentration. CONCLUSIONS: These
      results show that soybeans appear to be a good source of nutritional iron in
      marginally iron-deficient individuals. More study is needed on the effect of
      plant nodulation on the form of soybean iron, aimed at enhancing bioavailability
      to combat iron deficiency in at-risk populations.

PMID- 12499340
TI  - Lipophilic antioxidants in patients with phenylketonuria.
AB  - BACKGROUND: Low serum ubiquinone-10 concentrations have been described in
      phenylketonuric patients fed natural-protein-restricted diets. Such low
      concentrations may be related to increased free radical damage. OBJECTIVE: We
      evaluated the relation between low serum ubiquinone-10 concentrations and other
      lipophilic antioxidants (tocopherol and retinol), selenium, glutathione
      peroxidase activity, and malondialdehyde concentrations as a marker of lipid
      peroxidation. DESIGN: This was a cross-sectional study of 58 patients with
      phenylketonuria (aged 2-36 y; median: 13 y) under dietary treatment, 58 age
      matched control subjects, and 30 children with moderate hyperphenylalaninemia fed
      unrestricted diets (aged 3-17 y; median: 7.5 y). Serum ubiquinone-10
      concentrations were analyzed by HPLC with electrochemical detection. Serum
      retinol, serum tocopherol, and plasma malondialdehyde were analyzed by HPLC with
      ultraviolet detection. RESULTS: A significant positive correlation was observed
      between ubiquinone-10 and tocopherol (r = 0.510, P < 0.001) in the patients with
      phenylketonuria. After the patients were stratified into 2 groups according to
      ubiquinone-10 values, significantly lower concentrations of tocopherol were
      observed in group 1 (low ubiquinone values) than in group 2 (normal ubiquinone
      values), the hyperphenylalaninemic children, and the control group. Plasma
      malondialdehyde concentrations were significantly higher in group 1 than in the
      other groups. No significant differences between groups 1 and 2 were observed in
      daily intakes of selenium, ascorbate, tocopherol, or retinol. CONCLUSIONS: Plasma
      lipid peroxidation seems to be increased in phenylketonuria. Low concentrations
      of ubiquinone-10 could be associated with either excessive tocopherol consumption
      or high malondialdehyde concentrations in patients with phenylketonuria.

PMID- 12499341
TI  - Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency.
AB  - BACKGROUND: Ascorbate and glutathione play central roles in the defense against
      free radicals and oxidants that are implicated in chronic diseases. OBJECTIVE:
      The objective was to determine the ability of vitamin C supplements to modulate
      the concentration of glutathione in human lymphocytes. DESIGN: The effect of
      vitamin C supplements was determined in a sequential study with time points
      before supplementation, after 13 wk of vitamin C supplements (500 or 1000 mg/d),
      and after 13 wk of matching placebo. The supplementation group was selected on
      the basis of low plasma ascorbate (<33 mmol/L) and consisted of 48 healthy men
      and women, smokers and nonsmokers, aged 25-64 y. Ascorbate and glutathione were
      measured in purified lymphocytes. RESULTS: At baseline, the mean (+/-SD)
      concentration of plasma ascorbate was 19.5 +/- 7.2 micro mol/L, 22.5 micro mol/L
      below the median of normal distribution. The ascorbate concentration in plasma
      was linearly associated with that in lymphocytes (r = 0.53, P < 0.001). On
      supplementation with vitamin C, lymphocyte ascorbate increased by 51% (from 16.7
      +/- 4.9 to 25.3 +/- 6.9 nmol/mg protein; P < 0.001) and was accompanied by an
      increase of lymphocyte glutathione by 18% (from 22.5 +/- 4.5 to 26.6 +/- 6.5
      nmol/mg protein; P < 0.001). After placebo, the ascorbate and glutathione
      concentrations fell to near baseline concentrations (17.1 +/- 5.4 and 23.5 +/-
      6.4 nmol/mg protein, respectively). No significant interaction was observed for
      sex and smoking status. Finally, the changes in lymphocyte ascorbate after
      supplementation were strongly associated with changes in lymphocyte glutathione
      (r = 0.71, P < 0.001). The association suggests that every 1-mol change in
      ascorbate is accompanied by a change of approximately 0.5 mol in glutathione.
      CONCLUSION: Vitamin C supplements increase glutathione in human lymphocytes.

PMID- 12499342
TI  - Influence of reporting error on the relation between blood folate concentrations
      and reported folic acid-containing dietary supplement use among reproductive-aged
      women in the United States.
AB  - BACKGROUND: Folic acid intake is the most important predictor of blood folate
      concentrations among nonpregnant women, but the reporting of folic acid
      containing supplement use is subject to error. OBJECTIVE: We assessed the effect
      of reporting error of supplement use on blood folate concentrations. DESIGN: Data
      from the third National Health and Nutrition Examination Survey were analyzed.
      Respondents to that survey were asked twice about supplement use: ie, during the
      household interview, to recall use in the previous month, and during the physical
      examination, to recall use in the previous 24 h. To examine the effect of error
      reporting, we classified women (aged 15-44 y) into 5 groups according to
      supplement use in the previous month (nonusers, those ingesting < 400 micro g/d,
      and those ingesting >or= 400 micro g/d) and in the 24 h before the physical
      examination (yes or no). We expected nonappreciable differences in red blood cell
      (RBC) folate concentration by status of 24-h recall within the same category of
      previous-month use because RBC folate reflects long-term average consumption. We
      calculated covariate-adjusted means of serum and RBC folate concentrations.
      RESULTS: Among women who reported average daily use of >or= 400 micro g folic
      acid in the previous month, the adjusted mean RBC folate was 436.5 nmol/L (95%
      CI: 406.7, 466.3 nmol/L) in those who did not take the supplement in the previous
      24 h and 519.7 nmol/L (95% CI: 496.2, 543.2 nmol/L) in those who did do so (P <
      0.01). This significant difference indicates apparently erroneous reporting of
      supplement use in the previous month by some participants. CONCLUSION: The effect
      of reporting error on blood folate concentrations is important in interpreting
      survey results, evaluating health education campaigns, and identifying
      populations needing special education programs.

PMID- 12499343
TI  - Human serum 25-hydroxycholecalciferol response to extended oral dosing with
      cholecalciferol.
AB  - BACKGROUND: The cholecalciferol inputs required to achieve or maintain any given
      serum 25-hydroxycholecalciferol concentration are not known, particularly within
      ranges comparable to the probable physiologic supply of the vitamin. OBJECTIVES:
      The objectives were to establish the quantitative relation between steady state
      cholecalciferol input and the resulting serum 25-hydroxycholecalciferol
      concentration and to estimate the proportion of the daily requirement during
      winter that is met by cholecalciferol reserves in body tissue stores. DESIGN:
      Cholecalciferol was administered daily in controlled oral doses labeled at 0, 25,
      125, and 250 micro g cholecalciferol for approximately 20 wk during the winter to
      67 men living in Omaha (41.2 degrees N latitude). The time course of serum 25
      hydroxycholecalciferol concentration was measured at intervals over the course of
      treatment. RESULTS: From a mean baseline value of 70.3 nmol/L, equilibrium
      concentrations of serum 25-hydroxycholecalciferol changed during the winter
      months in direct proportion to the dose, with a slope of approximately 0.70
      nmol/L for each additional 1 micro g cholecalciferol input. The calculated oral
      input required to sustain the serum 25-hydroxycholecalciferol concentration
      present before the study (ie, in the autumn) was 12.5 micro g (500 IU)/d, whereas
      the total amount from all sources (supplement, food, tissue stores) needed to
      sustain the starting 25-hydroxycholecalciferol concentration was estimated at
      approximately 96 micro g (approximately 3800 IU)/d. By difference, the tissue
      stores provided approximately 78-82 micro g/d. CONCLUSIONS: Healthy men seem to
      use 3000-5000 IU cholecalciferol/d, apparently meeting > 80% of their winter
      cholecalciferol need with cutaneously synthesized accumulations from solar
      sources during the preceding summer months. Current recommended vitamin D inputs
      are inadequate to maintain serum 25-hydroxycholecalciferol concentration in the
      absence of substantial cutaneous production of vitamin D.

PMID- 12499344
TI  - Hyperhomocysteinemia and vitamin B-12 deficiency in elderly using Title IIIc
      nutrition services.
AB  - BACKGROUND: The effect of the folate food fortification program on the prevalence
      of hyperhomocysteinemia in the older population with coexisting vitamin B-12
      deficiency is not known. OBJECTIVE: The objective was to determine the prevalence
      of hyperhomocysteinemia and vitamin B-12 deficiency in elderly who were using
      Title IIIc nutrition services, after folate food fortification in the United
      States. DESIGN: Demographic, nutritional, cognitive, routine diagnostic, and
      serum methylmalonic acid (MMA) and total homocysteine (tHcy) tests were performed
      in a convenience sample of 103 elderly enrolled in nutrition service programs in
      rural northeast Georgia. A subgroup (n = 27) was treated with vitamin B-12, 2.5
      mg, and a multivitamin with 400 micro g folic acid, 2 mg vitamin B-6, and 27 mg
      ferrous fumarate. RESULTS: The total cohort included 103 participants (+/- SD
      age: 76.4 +/- 8.1; 80% female; 68% white, 32% African American). Vitamin B-12
      deficiency (serum vitamin B-12 < 258 pmol/L and MMA > 271 nmol/L) was present in
      23%. Mean serum folate was high, 39.3 nmol/L, and no subject had serum folate <
      6.8 nmol/L. Mean tHcy was 17.6 +/- 7.2 micro mol/L in vitamin B-12-deficient
      subjects and 10.8 +/- 3.6 micro mol/L in those who were nondeficient.
      Determinants of high tHcy were vitamin B-12 deficiency, high serum creatinine,
      and low red blood cell folate. Those with vitamin B-12 deficiency were more
      likely to have poor cognition (58% compared with 20%, P < 0.001) and anemia (38%
      compared with 18%, P = 0.042). High-dose oral B-12 therapy lowered mean MMA and
      tHcy by 49% and 32%, respectively. CONCLUSION: Vitamin B-12 deficiency was
      prevalent and was associated with poor cognition, anemia, and
      hyperhomocysteinemia.

PMID- 12499345
TI  - Effect of food fortification on folic acid intake in the United States.
AB  - BACKGROUND: The addition of folic acid to all enriched cereal-grain foods,
      mandated by the Food and Drug Administration (FDA), was initiated in January
      1998. Although this program was designed such that typical folate intakes would
      be increased by approximately 100 micro g/d and that the risk of intakes > 1000
      micro g/d (the FDA's safe upper limit of daily intake) would be minimal, its
      actual effect on folate intake has yet to be determined. OBJECTIVE: The objective
      was to estimate the effect of folic acid fortification on the amount of folate
      consumed by persons in the United States. DESIGN: Linear regression analysis of
      data from published studies was used to determine the relation between a chronic
      folic acid dose and the resulting increase in steady state concentrations of
      folate in plasma or serum. Using this regression equation and reverse prediction,
      we quantified the increase in folic acid intake from fortification required to
      achieve the increase in plasma or serum folate observed in published studies.
      RESULTS: The increase in circulating folate concentration was linearly related to
      folic acid intake over the range of 100-1000 micro g/d (r = 0.984, P < 0.0001).
      Predicted increases in folic acid intake from fortified food ranged from 215 to
      240 micro g/d. CONCLUSIONS: Typical intakes of folic acid from fortified foods
      are more than twice the level originally predicted. The effect of this much
      higher level of fortification must be carefully assessed, especially before calls
      for higher levels of fortification are considered.

PMID- 12499346
TI  - Supplementing lactating women with flaxseed oil does not increase docosahexaenoic
      acid in their milk.
AB  - BACKGROUND: Flaxseed oil is a rich source of 18:3n-3 (alpha-linolenic acid, or
      ALA), which is ultimately converted to 22:6n-3 (docosahexaenoic acid, or DHA), a
      fatty acid important for the development of the infant brain and retina.
      OBJECTIVE: The objective of this study was to determine the effect of flaxseed
      oil supplementation on the breast-milk, plasma, and erythrocyte contents of DHA
      and other n-3 fatty acids in lactating women. DESIGN: Seven women took 20 g
      flaxseed oil (10.7 g ALA) daily for 4 wk. Breast-milk and blood samples were
      collected weekly before, during, and after supplementation and were analyzed for
      fatty acid composition. RESULTS: Breast milk, plasma, and erythrocyte ALA
      increased significantly over time (P < 0.001) and after 2 and 4 wk of
      supplementation (P < 0.05). Over time, 20:5n-3 (eicosapentaenoic acid, or EPA)
      increased significantly in breast milk (P = 0.004) and in plasma (P < 0.001). In
      addition, plasma EPA increased significantly (P < 0.05) after 2 and 4 wk of
      supplementation. There were significant increases over time in breast-milk 22:5n
      3 (docosapentaenoic acid, or DPA) (P < 0.02), plasma DPA (P < 0.001), and
      erythrocyte DPA (P < 0.01). No significant changes were observed in breast-milk,
      plasma, or erythrocyte DHA contents after flaxseed oil supplementation.
      CONCLUSIONS: Dietary flaxseed oil increased the breast-milk, plasma, and
      erythrocyte contents of the n-3 fatty acids ALA, EPA, and DPA but had no effect
      on breast-milk, plasma, or erythrocyte DHA contents.

PMID- 12499347
TI  - Iron supplementation improves iron status and reduces morbidity in children with
      or without upper respiratory tract infections: a randomized controlled study in
      Colombo, Sri Lanka.
AB  - BACKGROUND: Iron deficiency anemia and recurrent infections are common among
      children of low socioeconomic status. OBJECTIVE: The objective was to evaluate
      the effects of iron supplementation on iron status and morbidity in children with
      or without infection. DESIGN: Children aged 5-10 y were recruited for a
      randomized, controlled, double-blind study from outpatients attending the
      Children's Hospital, Colombo, Sri Lanka. Clinical, inflammatory, nutritional, and
      iron statuses were determined at baseline and after the intervention. Children
      with a history of recurrent upper respiratory tract infections (URTIs) and with
      laboratory and clinical evidence of a current URTI constituted the infection
      group (n = 179), and children without infection constituted the control group (n
      = 184). Subjects in both groups were supplemented with ferrous sulfate (60 mg Fe)
      or placebo once daily for 8 wk. Morbidity from URTIs, the number of
      gastrointestinal infections, and compliance were recorded every 2 wk. RESULTS:
      The overall prevalence of anemia was 52.6%. Iron supplementation significantly
      improved iron status by increasing hemoglobin (P < 0.001) and serum ferritin (P <
      0.001) concentrations from baseline values in the children with or without
      infection. There was no significant improvement in iron status in the children
      who received placebo. In both the infection group and the control group, the mean
      number of URTI episodes and the total number of days sick with an URTI during the
      period of intervention were significantly lower (P < 0.005 and P < 0.001,
      respectively) in the children who received iron supplements than in those who
      received placebo. CONCLUSION: Iron supplementation significantly improves iron
      status and reduces morbidity from URTIs in children with or without infection.

PMID- 12499348
TI  - Titers of antibody to common pathogens: relation to food-based interventions in
      rural Kenyan schoolchildren.
AB  - BACKGROUND: Undernutrition is widely perceived to affect the development of an
      effective immune system. OBJECTIVE: We used a mini-analysis system to quantitate
      antibody titers and evaluate the sera of 200 Kenyan schoolchildren for antibodies
      to Helicobacter pylori [isotypes of immunoglobulins A (IgA), G (IgG), and M
      (IgM)], hepatitis A virus, rotavirus, tetanus toxoid (IgG), and a panel of
      recombinant malarial antigens (MSP1(19), MSP2, Ag512, MSP4, and MSP5). DESIGN:
      Children participated in a school-based feeding intervention with meat, milk, or
      nonanimal-source foods or in a nonintervention control group. Microvolumes (200
      mL) of sera were analyzed at baseline and after 1 y. RESULTS: Nearly all children
      had elevated titers of antibody to H. pylori, hepatitis A virus, rotavirus, and
      malaria at the outset, despite a high prevalence of apparent biochemical
      micronutrient deficiencies and stunting, but many had titers of tetanus toxoid
      IgG antibodies below the protective concentration. Children with low hemoglobin
      had a greater proportion of elevated H. pylori IgM antibody titers at baseline,
      which suggests that current infection with H. pylori may be associated with
      anemia. Compared with the control subjects, only the group eating meat had a
      significant increase in H. pylori IgM antibodies during the intervention (P =
      0.019). No other group comparisons with the control subjects were statistically
      significant. The additional finding that the sera of some children showed
      inadequate tetanus-protective antibodies, despite immunization, suggests that the
      vaccination program was suboptimal. CONCLUSIONS: A large battery of immune assays
      can be performed on microvolumes of sera. Furthermore, despite evidence of
      malnutrition, children do develop significant antibody-mediated responses to
      common pathogens.

PMID- 12499349
TI  - Plasma taurine concentrations increase after enteral glutamine supplementation in
      trauma patients and stressed rats.
AB  - BACKGROUND: Taurine is a unique amino acid with antioxidant and osmolytic
      properties. Glutamine serves as the preferred fuel for the gut, liver, and immune
      cells and as a precursor for antioxidants. Trauma patients have low glutamine
      concentrations. OBJECTIVES: We investigated the effect of glutamine-enriched
      enteral nutrition on plasma taurine concentrations in patients with severe trauma
      (injury severity score >20). Additionally, plasma taurine concentrations and
      organ fluxes were studied in a stressed rat model. DESIGN: Twenty-nine patients
      with multiple trauma received glutamine-enriched nutrition and 31 patients
      received isocaloric, isonitrogenous control solution for 5 d. Plasma taurine and
      glutamine concentrations were measured. Male Wistar rats (250-300 g) received a
      glutamine-enriched diet (12%, by wt) or a control solution for 2 wk. Plasma
      taurine concentrations were measured. Taurine fluxes and fractional extraction
      rates in the liver, kidneys, and gut were assessed with a radioactive microsphere
      technique. RESULTS: Both patient groups had low taurine concentrations on day 1.
      From day 3 onward, the glutamine-fed patients had significantly higher taurine
      concentrations. Rats fed a glutamine-enriched diet had significantly higher
      plasma taurine concentrations than did the controls. A high taurine uptake was
      found in the liver, kidneys, and gut of the glutamine-fed rats. Fractional
      extraction rates were not significantly different between the rat groups.
      CONCLUSIONS: Glutamine enrichment increases plasma taurine in trauma patients and
      in stressed rats. Because of increased availability, organ fluxes showed a higher
      taurine uptake in the liver, kidneys, and gut. The reduction in morbidity with
      glutamine enrichment could be explained in part by increased taurine
      availability.

PMID- 12499350
TI  - Milk intake during childhood and adolescence, adult bone density, and
      osteoporotic fractures in US women.
AB  - BACKGROUND: Calcium supplements increase bone mass in children, but the effect
      does not persist once supplementation is discontinued. OBJECTIVE: The objective
      of this study was to determine whether milk intake during childhood and
      adolescence, when controlled for current calcium intake, is associated with adult
      bone mass (ie, bone mineral content), bone mineral density, and the incidence of
      osteoporotic fracture. DESIGN: We used data from the third National Health and
      Nutrition Examination Survey of 3251 non-Hispanic, white women age >or=20 y. Bone
      density was measured at the hip. History of fracture of the hip, spine, or
      forearm was classified as a lifetime fracture (occurring after age 13 y) or an
      osteoporotic fracture (occurring after age 50 y). Subjects reported frequency of
      milk consumption during childhood (aged 5-12 y) and during adolescence (aged 13
      17 y). Regression models controlled for weight, height, age, menopause and use of
      estrogen, physical activity, smoking, and current calcium intake. RESULTS: Among
      women aged 20-49 y, bone mineral content was 5.6% lower in those who consumed <1
      serving of milk/wk (low intake) than in those who consumed >1 serving/d (high
      intake) during childhood (P < 0.01). Low milk intake during adolescence was
      associated with a 3% reduction in hip bone mineral content and bone mineral
      density (P < 0.02). Among women aged >or=50 y, there was a nonlinear association
      between milk intake during childhood and adolescence and hip bone mineral content
      and bone mineral density (P < 0.04). Low milk intake during childhood was
      associated with a 2-fold greater risk of fracture (P < 0.05). CONCLUSION: Women
      with low milk intake during childhood and adolescence have less bone mass in
      adulthood and greater risk of fracture.

PMID- 12499351
TI  - Concentrative sorting of secretory cargo proteins into COPII-coated vesicles.
AB  - Here, we show that efficient transport of membrane and secretory proteins from
      the ER of Saccharomyces cerevisiae requires concentrative and signal-mediated
      sorting. Three independent markers of bulk flow transport out of the ER indicate
      that in the absence of an ER export signal, molecules are inefficiently captured
      into coat protein complex II (COPII)-coated vesicles. A soluble secretory
      protein, glycosylated pro-alpha-factor (gpalphaf), was enriched approximately 20
      fold in these vesicles relative to bulk flow markers. In the absence of Erv29p, a
      membrane protein that facilitates gpalphaf transport (Belden and Barlowe, 2001),
      gpalphaf is packaged into COPII vesicles as inefficiently as soluble bulk flow
      markers. We also found that a plasma membrane protein, the general amino acid
      permease (Gap1p), is enriched approximately threefold in COPII vesicles relative
      to membrane phospholipids. Mutation of a diacidic sequence present in the COOH
      terminal cytosolic domain of Gap1p eliminated concentrative sorting of this
      protein.

PMID- 12499352
TI  - Spatial and temporal association of Bax with mitochondrial fission sites, Drp1,
      and Mfn2 during apoptosis.
AB  - We find that Bax, a proapoptotic member of the Bcl-2 family, translocates to
      discrete foci on mitochondria during the initial stages of apoptosis, which
      subsequently become mitochondrial scission sites. A dominant negative mutant of
      Drp1, Drp1K38A, inhibits apoptotic scission of mitochondria, but does not inhibit
      Bax translocation or coalescence into foci. However, Drp1K38A causes the
      accumulation of mitochondrial fission intermediates that are associated with
      clusters of Bax. Surprisingly, Drp1 and Mfn2, but not other proteins implicated
      in the regulation of mitochondrial morphology, colocalize with Bax in these foci.
      We suggest that Bax participates in apoptotic fragmentation of mitochondria.

PMID- 12499353
TI  - A role for PKC-epsilon in Fc gammaR-mediated phagocytosis by RAW 264.7 cells.
AB  - Protein kinase C (PKC) plays a prominent role in immune signaling, and the
      paradigms for isoform selective signaling are beginning to be elucidated. Real
      time microscopy was combined with molecular and biochemical approaches to
      demonstrate a role for PKC- epsilon in Fc gamma receptor (Fc gammaR)-dependent
      phagocytosis. RAW 264.7 macrophages were transfected with GFP-conjugated PKC
      isoforms, and GFP movement was followed during phagocytosis of fluorescent IgG
      opsonized beads. PKC- epsilon, but not PKC-delta, concentrated around the beads.
      PKC- epsilon accumulation was transient; apparent as a "flash" on target
      ingestion. Similarly, endogenous PKC- epsilon was specifically recruited to the
      nascent phagosomes in a time-dependent manner. Overexpression of PKC- epsilon,
      but not PKC-alpha, PKC-delta, or PKC-gamma enhanced bead uptake 1.8-fold.
      Additionally, the rate of phagocytosis in GFP PKC- epsilon expressors was twice
      that of cells expressing GFP PKC-delta. Expression of the regulatory domain (
      epsilon RD) and the first variable region ( epsilon V1) of PKC- epsilon inhibited
      uptake, whereas the corresponding PKC-delta region had no effect. Actin
      polymerization was enhanced on expression of GFP PKC- epsilon and epsilon RD, but
      decreased in cells expressing epsilon V1, suggesting that the epsilon RD and
      epsilon V1 inhibition of phagocytosis is not due to effects on actin
      polymerization. These results demonstrate a role for PKC- epsilon in Fc gammaR
      mediated phagocytosis that is independent of its effects on actin assembly.

PMID- 12499354
TI  - Ribonucleoprotein-dependent localization of the yeast class V myosin Myo4p.
AB  - Class V myosins are motor proteins with functions in vesicle transport, organelle
      segregation, and RNA localization. Although they have been extensively studied,
      only little is known about the regulation of their spatial distribution. Here we
      demonstrate that a GFP fusion protein of the budding yeast class V myosin Myo4p
      accumulates at the bud cortex and is a component of highly dynamic cortical
      particles. Bud-specific enrichment depends on Myo4p's association with its cargo,
      a ribonucleoprotein complex containing the RNA-binding protein She2p. Cortical
      accumulation of Myo4p at the bud tip can be explained by a transient retention
      mechanism that requires SHE2 and, apparently, localized mRNAs bound to She2p. A
      mutant She2 protein that is unable to recognize its cognate target mRNA, ASH1,
      fails to localize Myo4p. Mutant She2p accumulates inside the nucleus, indicating
      that She2p shuttles between the nucleus and cytoplasm and is exported in an RNA
      dependent manner. Consistently, inhibition of nuclear mRNA export results in
      nuclear accumulation of She2p and cytoplasmic Myo4p mislocalization. Loss of
      She2p can be complemented by direct targeting of a heterologous lacZ mRNA to a
      complex of Myo4p and its associated adaptor She3p, suggesting that She2p's
      function in Myo4p targeting is to link an mRNA to the motor complex.

PMID- 12499355
TI  - The prepower stroke conformation of myosin V.
AB  - We have used electron microscopy and single-particle image processing to study
      head conformation in myosin V molecules. We find that in the presence of ATP,
      many heads have a sharply angled conformation that is rare in its absence. The
      sharply angled conformation is similar to a myosin II atomic structure proposed
      to mimic the prepower stroke state. The leading head in molecules attached to
      actin by both heads has a similar conformation, but is also sharply angled in a
      second plane by tethering through the trail head. The lead head lever joins the
      motor domain approximately 5 nm axially from where it joins the trail motor.
      These positions locate the converter subdomain and show the lead motor is in the
      prepower stroke conformation. Tethering by the trail head places the lead head
      motor domain at the correct axial position along the actin for binding, but at
      the wrong orientation. Attachment is achieved either by bending the lead head
      lever throughout its length or at the pliant point. The microscopy shows that
      most of the walking stride is produced by changes in lever angle brought about by
      converter movement, but is augmented by distortion produced by thermal energy.

PMID- 12499356
TI  - Direct regulation of Arp2/3 complex activity and function by the actin binding
      protein coronin.
AB  - Mechanisms for activating the actin-related protein 2/3 (Arp2/3) complex have
      been the focus of many recent studies. Here, we identify a novel mode of Arp2/3
      complex regulation mediated by the highly conserved actin binding protein
      coronin. Yeast coronin (Crn1) physically associates with the Arp2/3 complex and
      inhibits WA- and Abp1-activated actin nucleation in vitro. The inhibition occurs
      specifically in the absence of preformed actin filaments, suggesting that Crn1
      may restrict Arp2/3 complex activity to the sides of filaments. The inhibitory
      activity of Crn1 resides in its coiled coil domain. Localization of Crn1 to actin
      patches in vivo and association of Crn1 with the Arp2/3 complex also require its
      coiled coil domain. Genetic studies provide in vivo evidence for these
      interactions and activities. Overexpression of CRN1 causes growth arrest and
      redistribution of Arp2 and Crn1p into aberrant actin loops. These defects are
      suppressed by deletion of the Crn1 coiled coil domain and by arc35-26, an allele
      of the p35 subunit of the Arp2/3 complex. Further in vivo evidence that coronin
      regulates the Arp2/3 complex comes from the observation that crn1 and arp2
      mutants display an allele-specific synthetic interaction. This work identifies a
      new form of regulation of the Arp2/3 complex and an important cellular function
      for coronin.

PMID- 12499357
TI  - Intermediate filament-membrane attachments function synergistically with actin
      dependent contacts to regulate intercellular adhesive strength.
AB  - By tethering intermediate filaments (IFs) to sites of intercellular adhesion,
      desmosomes facilitate formation of a supercellular scaffold that imparts
      mechanical strength to a tissue. However, the role IF-membrane attachments play
      in strengthening adhesion has not been directly examined. To address this
      question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP)
      mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the
      plasma membrane and led to dissociation of IFs from the junctional plaque,
      without altering total or cell surface distribution of adherens junction or
      desmosomal proteins. However, a specific decrease in the detergent-insoluble pool
      of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP
      expressing cell aggregates in suspension or substrate-released cell sheets
      readily dissociated when subjected to mechanical stress whereas controls remained
      largely intact. Dissociation occurred without lactate dehydrogenase release,
      suggesting that loss of tissue integrity was due to reduced adhesion rather than
      increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation
      were also more weakly adherent compared with normal keratinocytes. When used in
      combination with DPNTP, latrunculin A, which disassembles actin filaments and
      disrupts adherens junctions, led to dissociation up to an order of magnitude
      greater than either treatment alone. These data provide direct in vitro evidence
      that IF-membrane attachments regulate adhesive strength and suggest furthermore
      that actin- and IF-based junctions act synergistically to strengthen adhesion.

PMID- 12499358
TI  - The Cdc37 protein kinase-binding domain is sufficient for protein kinase activity
      and cell viability.
AB  - Cdc37 is a molecular chaperone required for folding of protein kinases. It
      functions in association with Hsp90, although little is known of its mechanism of
      action or where it fits into a folding pathway involving other Hsp90
      cochaperones. Using a genetic approach with Saccharomyces cerevisiae, we show
      that CDC37 overexpression suppressed a defect in v-Src folding in yeast deleted
      for STI1, which recruits Hsp90 to misfolded clients. Expression of CDC37
      truncation mutants that were deleted for the Hsp90-binding site stabilized v-Src
      and led to some folding in both sti1Delta and hsc82Delta strains. The protein
      kinase-binding domain of Cdc37 was sufficient for yeast cell viability and
      permitted efficient signaling through the yeast MAP kinase-signaling pathway. We
      propose a model in which Cdc37 can function independently of Hsp90, although its
      ability to do so is restricted by its normally low expression levels. This may be
      a form of regulation by which cells restrict access to Cdc37 until it has passed
      through a triage involving other chaperones such as Hsp70 and Hsp90.

PMID- 12499359
TI  - Regulation of Rac1 activation by the low density lipoprotein receptor-related
      protein.
AB  - The low density lipoprotein receptor-related protein (LRP-1) binds and mediates
      the endocytosis of multiple ligands, transports the urokinase-type plasminogen
      activator receptor (uPAR) and other membrane proteins into endosomes, and binds
      intracellular adaptor proteins involved in cell signaling. In this paper, we show
      that in murine embryonic fibroblasts (MEFs) and L929 cells, LRP-1 functions as a
      major regulator of Rac1 activation, and that this activity depends on uPAR. LRP-1
      deficient MEFs demonstrated increased Rac1 activation compared with LRP-1
      expressing MEFs, and this property was reversed by expressing the VLDL receptor,
      a member of the same gene family as LRP-1, with overlapping ligand-binding
      specificity. Neutralizing the activity of LRP-1 with receptor-associated protein
      (RAP) increased Rac1 activation and cell migration in MEFs and L929 cells. The
      same parameters were unaffected by RAP in uPAR-/- MEFs, prepared from uPAR gene
      knockout embryos, and in uPAR-deficient LM-TK- cells. Untreated uPAR+/+ MEFs
      demonstrated substantially increased Rac1 activation compared with uPAR-/- MEFs.
      In addition to Rac1, LRP-1 suppressed activation of extracellular signal
      regulated kinase (ERK) in MEFs; however, it was Rac1 (and not ERK) that was
      responsible for the effects of LRP-1 on MEF migration. Thus, LRP-1 regulates two
      signaling proteins in the same cell (Rac1 and ERK), both of which may impact on
      cell migration. In uPAR-negative cells, LRP-1 neutralization does not affect Rac1
      activation, and other mechanisms by which LRP-1 may regulate cell migration are
      not unmasked.

PMID- 12499360
TI  - Migration of nerve growth cones requires detergent-resistant membranes in a
      spatially defined and substrate-dependent manner.
AB  - Motility of nerve growth cones (GCs) is regulated by region-specific activities
      of cell adhesion molecules (CAMs). CAM activities could be modified by their
      localization to detergent-resistant membranes (DRMs), specialized microdomains
      enriched in signaling molecules. This paper deals with a question of whether DRMs
      are involved in GC migration stimulated by three CAMs; L1, N-cadherin (Ncad), and
      beta1 integrin. We demonstrate that L1 and Ncad are present in DRMs, whereas
      beta1 integrin is exclusively detected in non-DRMs of neurons and that
      localization of L1 and Ncad to DRMs is developmentally regulated. GC migration
      mediated by L1 and Ncad but not by beta1 integrin is inhibited after DRM
      disruption by micro-scale chromophore-assisted laser inactivation (micro-CALI) of
      GM1 gangliosides or by pharmacological treatments that deplete cellular
      cholesterol or sphingolipids, essential components for DRMs. Characteristic
      morphology of GCs induced by L1 and Ncad is also affected by micro-CALI-mediated
      DRM disruption. Micro-CALI within the peripheral domain of GCs, or even within
      smaller areas such as the filopodia and the lamellipodia, is sufficient to impair
      their migration. However, micro-CALI within the central domain does not affect GC
      migration. These results demonstrate the region-specific involvement of DRMs in
      CAM-dependent GC behavior.

PMID- 12499361
TI  - SadA, a novel adhesion receptor in Dictyostelium.
AB  - Little is known about cell-substrate adhesion and how motile and adhesive forces
      work together in moving cells. The ability to rapidly screen a large number of
      insertional mutants prompted us to perform a genetic screen in Dictyostelium to
      isolate adhesion-deficient mutants. The resulting substrate adhesion-deficient
      (sad) mutants grew in plastic dishes without attaching to the substrate. The
      cells were often larger than their wild-type parents and displayed a rough
      surface with many apparent blebs. One of these mutants, sadA-, completely lacked
      substrate adhesion in growth medium. The sadA- mutant also showed slightly
      impaired cytokinesis, an aberrant F-actin organization, and a phagocytosis
      defect. Deletion of the sadA gene by homologous recombination recreated the
      original mutant phenotype. Expression of sadA-GFP in sadA-null cells restored the
      wild-type phenotype. In sadA-GFP-rescued mutant cells, sadA-GFP localized to the
      cell surface, appropriate for an adhesion molecule. SadA contains nine putative
      transmembrane domains and three conserved EGF-like repeats in a predicted
      extracellular domain. The EGF repeats are similar to corresponding regions in
      proteins known to be involved in adhesion, such as tenascins and integrins. Our
      data combined suggest that sadA is the first substrate adhesion receptor to be
      identified in Dictyostelium.

PMID- 12499362
TI  - GlcNAc 2-epimerase can serve a catabolic role in sialic acid metabolism.
AB  - Sialic acid is a major determinant of carbohydrate-receptor interactions in many
      systems pertinent to human health and disease. N-Acetylmannosamine (ManNAc) is
      the first committed intermediate in the sialic acid biosynthetic pathway; thus,
      the mechanisms that control intracellular ManNAc levels are important regulators
      of sialic acid production. UDP-GlcNAc 2-epimerase and GlcNAc 2-epimerase are two
      enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc, respectively.
      Whereas the former enzyme has been shown to direct metabolic flux toward sialic
      acid in vivo, the function of the latter enzyme is unclear. Here we study the
      effects of GlcNAc 2-epimerase expression on sialic acid production in cells. A
      key tool we developed for this study is a cell-permeable, small molecule
      inhibitor of GlcNAc 2-epimerase designed based on mechanistic principles. Our
      results indicate that, unlike UDP-GlcNAc 2-epimerase, which promotes biosynthesis
      of sialic acid, GlcNAc 2-epimerase can serve a catabolic role, diverting
      metabolic flux away from the sialic acid pathway.

PMID- 12499363
TI  - The catabolism of amino acids to long chain and complex alcohols in Saccharomyces
      cerevisiae.
AB  - The catabolism of phenylalanine to 2-phenylethanol and of tryptophan to
      tryptophol were studied by (13)C NMR spectroscopy and gas chromatography-mass
      spectrometry. Phenylalanine and tryptophan are first deaminated (to 3
      phenylpyruvate and 3-indolepyruvate, respectively) and then decarboxylated. This
      decarboxylation can be effected by any of Pdc1p, Pdc5p, Pdc6p, or Ydr380wp;
      Ydl080cp has no role in the catabolism of either amino acid. We also report that
      in leucine catabolism Ydr380wp is the minor decarboxylase. Hence, all amino acid
      catabolic pathways studied to date use a subtly different spectrum of
      decarboxylases from the five-membered family that comprises Pdc1p, Pdc5p, Pdc6p,
      Ydl080cp, and Ydr380wp. Using strains containing all possible combinations of
      mutations affecting the seven AAD genes (putative aryl alcohol dehydrogenases),
      five ADH genes, and SFA1, showed that the final step of amino acid catabolism
      (conversion of an aldehyde to a long chain or complex alcohol) can be
      accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p,
      Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.)

PMID- 12499364
TI  - Characterization and in vivo functional analysis of splice variants of cypher.
AB  - Previously, we reported two splice variants of Cypher, a striated muscle-specific
      PDZLIM domain protein, Cypher1 and Cypher2. We have now characterized four
      additional splice isoforms, two of which are novel. The six isoforms can be
      divided into skeletal or cardiac specific classes, based on the inclusion of
      skeletal or cardiac specific domains. Short and long isoforms share an N-terminal
      PDZ domain, but the three C-terminal LIM domains are unique to long isoforms. By
      RNA and protein analysis, we have demonstrated that Cypher isoforms are
      developmentally regulated in both skeletal and cardiac muscle. We have previously
      shown that knockout of Cypher is neonatal lethal. To investigate the function of
      splice variants in vivo, we have performed a rescue experiment of the Cypher null
      mutant by replacing the endogenous Cypher gene with cDNAs encoding either a short
      or long skeletal muscle isoform. In contrast to Cypher null mice, a percentage of
      mice that express only a short or a long skeletal muscle-specific isoform can
      survive to at least 1 year of age. Although surviving mice exhibit muscle
      pathology, these results suggest that either isoform is sufficient to rescue the
      lethality associated with the absence of Cypher.

PMID- 12499365
TI  - Identification of protein kinase C isozymes responsible for the phosphorylation
      of photoreceptor-specific RGS9-1 at Ser475.
AB  - Inactivation of the visual G-protein transducin by GTP hydrolysis is regulated by
      the GTPase-accelerating protein (GAP) RGS9-1. Regulation of RGS9-1 itself is
      poorly understood, but we found previously that it is subject to a light- and
      Ca(2+)-sensitive phosphorylation on Ser(475). Because there are much higher RGS9
      1 levels in cones than in rods, we investigated whether Ser(475) is
      phosphorylated in rods using Coneless mice and found that both the
      phosphorylation and its regulation by light occur in rods. Therefore, we used rod
      outer segments as the starting material for the purification of RGS9-1 kinase
      activity. Two major peaks of activity corresponded to protein kinase C (PKC)
      isozymes, PKCalpha and PKCtheta. A synthetic peptide corresponding to the
      Ser(475) RGS9-1 sequence and RGS9-1 were substrates for recombinant PKCalpha and
      PKCtheta. This phosphorylation was removed efficiently by protein phosphatase 2A,
      an endogenous phosphatase in rod outer segments, but not by PP1 or PP2B.
      Phosphorylation of RGS9-1 by PKC had little effect on its activity in solution
      but significantly decreased its affinity for its membrane anchor protein and GAP
      enhancer, RGS9-1 anchor protein (R9AP). PKCtheta immunostaining was at higher
      levels in cone outer segments than in rod outer segments, as was found for the
      components of the RGS9-1 GAP complex. Thus, PKC-mediated phosphorylation of RGS9
      1 represents a potential mechanism for feedback control of the kinetics of
      photoresponse recovery in both rods and cones, with this mechanism probably
      especially important in cones.

PMID- 12499366
TI  - Dynamin-like protein 1 is involved in peroxisomal fission.
AB  - The mammalian dynamin-like protein 1 (DLP1), a member of the dynamin family of
      large GTPases, possesses mechanochemical properties known to constrict and
      tubulate membranes. In this study, we have combined two experimental approaches,
      induction of peroxisome proliferation by Pex11pbeta and expression of dominant
      negative mutants, to test whether DLP1 plays a role in peroxisomal growth and
      division. We were able to localize DLP1 in spots on tubular peroxisomes in HepG2
      cells. In addition, immunoblot analysis revealed the presence of DLP1 in highly
      purified peroxisomal fractions from rat liver and an increase of DLP1 after
      treatment of rats with the peroxisome proliferator bezafibrate. Expression of a
      dominant negative DLP1 mutant deficient in GTP hydrolysis (K38A) either alone or
      in combination with Pex11pbeta caused the appearance of tubular peroxisomes but
      had no influence on their intracellular distribution. In co-expressing cells, the
      formation of tubulo-reticular networks of peroxisomes was promoted, and
      peroxisomal division was completely inhibited. These findings were confirmed by
      silencing of DLP1 using siRNA. We propose a direct role for the dynamin-like
      protein DLP1 in peroxisomal fission and in the maintenance of peroxisomal
      morphology in mammalian cells.

PMID- 12499367
TI  - Dynamic chromatin alterations triggered by natural and synthetic activation
      domains.
AB  - The activation domains (ADs) of transcription activators recruit a multiplicity
      of enzymatic activities to gene promoters. The mechanisms by which such
      recruitment takes place are not well understood. Using chromatin
      immunoprecipitation, we demonstrate dynamic alterations in the abundance of
      histones H2A, H3, and H4 at promoters of genes regulated by the HSF and Gal4
      activators of Saccharomyces cerevisiae. Transcriptional activation of these
      genes, particularly those regulated by HSF, is accompanied by a significant
      reduction in both acetylated and unacetylated histones at promoters and may
      involve the transient displacement of histone octamers. To gain insight into the
      function of ADs, we conducted a genetic screen to identify polypeptides that
      could substitute for the 340-residue C-terminal activator of HSF and rescue the
      temperature sensitivity caused by its deletion. We found that the ts(-) phenotype
      of HSF(1-493) could be complemented by peptides as short as 11 amino acids. Such
      peptides are enriched in acidic and hydrophobic residues, and exhibit both trans
      activating and chromatin-modifying activities when fused to the Gal4 DNA-binding
      domain. We also demonstrate that a previously identified 14-amino acid histone H3
      binding module of human CTF1/NF1, which is similar to synthetic ADs, can
      substitute for the HSF C-terminal activator in conferring temperature resistance
      and can mediate the modification of promoter chromatin structure. Possible
      mechanisms of AD function, including one involving direct interactions with
      histones, are discussed.

PMID- 12499368
TI  - DNA-dependent acetylation of p53 by the transcription coactivator p300.
AB  - Reconstitution of the stages in the assembly of the p300.p53 transcription
      complex has identified a novel type of DNA-dependent regulation of p300-catalyzed
      acetylation. Phosphorylation at the CHK2 site (Ser(20)) in the N-terminal
      activation domain of p53 stabilized p300 binding. The phosphopeptide binding
      activity of p300 was mapped in vitro to two domains: the C-terminal IBiD domain
      and the N-terminal IHD domain (IBiD homology domain). The IHD or IBiD minidomains
      can bind to the p53 activation domain in vivo as determined using the mammalian
      two-hybrid VP16-GAL4 luciferase reporter assay. The IHD and IBiD minidomains of
      p300 also functioned as dominant negative inhibitors of p53-dependent
      transcription in vivo. Upon examining the affects of p300 binding on substrate
      acetylation, we found that the p53 consensus site DNA promotes a striking
      increase in p53 acetylation in vitro. Co-transfection into cells of the p53 gene
      and plasmid DNA containing the consensus DNA binding site of p53 activated DNA
      dependent acetylation of p53 in vivo. The phosphopeptide binding activity of p300
      is critical for DNA-dependent acetylation, as p53 acetylation was inhibited by
      phospho-Ser(20) peptides. Consensus site DNA-dependent acetylation of p53
      stabilized the p300.p53 protein complex, whereas basal acetylation of p53 by p300
      in the presence of nonspecific DNA resulted in p300 dissociation. These data
      identify at least three distinct stages in the assembly of a p300.p53 complex: 1)
      p300 docking to the activation domain of p53 via the IBiD and/or IHD domains; 2)
      DNA-dependent acetylation of p53; and 3) stabilization of the p300.p53(AC)
      complex after acetylation. The ability of DNA to act as an allosteric ligand to
      activate substrate acetylation identifies a conformational constraint that can be
      placed on the p300-acetylation reaction that is likely to be an amplification
      signal and influence protein-protein contacts at a promoter.

PMID- 12499369
TI  - NFBD1/KIAA0170 is a chromatin-associated protein involved in DNA damage signaling
      pathways.
AB  - NFBD1/KIAA0170 is a nuclear factor with an N-terminal FHA (forkhead-associated)
      domain and a tandem repeat of BRCT (breast cancer susceptibility gene-1 C
      terminus) domains, both of which are present in a number of proteins involved in
      DNA repair and/or DNA damage signaling pathways. We have investigated the
      association of NFBD1 with DNA damage responses. We found that the NFBD1
      transcript is abundant in the testis relative to other tissues. NFBD1 is a
      chromatin-associated protein and is modified in G(2)/M phase or after DNA damage.
      NFBD1 phosphorylation in response to ionizing radiation (IR) was ATM-dependent.
      NFBD1 exhibited diffuse nuclear staining in the majority of untreated cells
      analyzed by indirect immunofluorescence and formed discrete nuclear foci after
      exposure to IR, UV radiation, and hydroxyurea treatment. IR induced NFBD1 foci
      within 1 min. The foci colocalized with gamma-H2AX foci, which have been
      previously shown to localize at sites of DNA double-strand breaks. IR-induced
      NFBD1 foci also colocalized with 53BP1 and MRE11/RAD50 foci. Taken together,
      these results suggest that NFBD1 is a mediator of DNA damage-dependent signaling.

PMID- 12499370
TI  - Mechanism of minus strand strong stop transfer in HIV-1 reverse transcription.
AB  - Retrovirus minus strand strong stop transfer (minus strand transfer) requires
      reverse transcriptase-associated RNase H, R sequence homology, and viral
      nucleocapsid protein. The minus strand transfer mechanism in human
      immunodeficiency virus-1 was examined in vitro with purified protein and
      substrates. Blocking donor RNA 5'-end cleavage inhibited transfers when template
      homology was 19 nucleotides (nt) or less. Cleavage of the donor 5'-end occurred
      prior to formation of transfer products. This suggests that when template
      homology is short, transfer occurs through a primer terminus switch-initiated
      mechanism, which requires cleavage of the donor 5' terminus. On templates with 26
      nt and longer homology, transfer occurred before cleavage of the donor 5'
      terminus. Transfer was unaffected when donor 5'-end cleavages were blocked but
      was reduced when internal cleavages within the donor were restricted. Based on
      the overall data, we conclude that in human immunodeficiency virus-1, which
      contains a 97-nt R sequence, minus strand transfer occurs through an acceptor
      invasion-initiated mechanism. Transfer is initiated at internal regions of the
      homologous R sequence without requiring cleavage at the donor 5'-end. The
      acceptor invades at gaps created by reverse transcriptase-RNase H in the donor
      cDNA hybrid. The fragmented donor is eventually strand-displaced by the acceptor,
      completing the transfer.

PMID- 12499371
TI  - Structural basis for peptide binding in protein kinase A. Role of glutamic acid
      203 and tyrosine 204 in the peptide-positioning loop.
AB  - For optimal activity the catalytic subunit of cAMP-dependent protein kinase
      requires a phosphate on Thr-197. This phosphate anchors the activation loop in
      the proper conformation and contributes to catalytic efficiency by enhancing the
      phosphoryl transfer rate and increasing the affinity for ATP (1). The crystal
      structure of the catalytic subunit bound to ATP, and the inhibitor peptide, IP20,
      highlights the contacts made by the Thr-197 phosphate as well as the role
      adjacent residues play in contacting the substrate peptide. Glu-203 and Tyr-204
      interact with arginines in the consensus sequence of PKA substrates at the P-6
      and P-2 positions, respectively. To assess the contribution that each residue
      makes to peptide recognition, the kinetic properties of three mutant proteins
      (E203A, Y204A, and Y204F) were monitored using multiple peptide substrates. The
      canonical peptide substrate, Kemptide, as well as a longer 9-residue peptide and
      corresponding peptides with alanine substitutions at the P-6 and P-2 positions
      were used. While the effect of Glu-203 is more localized to the P-6 site, Tyr-204
      contributes to global peptide recognition. An aromatic hydrophobic residue is
      essential for optimal peptide recognition and is conserved throughout the protein
      kinase family.

PMID- 12499372
TI  - The alpha-helical D1 domain of the tobacco bZIP transcription factor BZI-1
      interacts with the ankyrin-repeat protein ANK1 and is important for BZI-1
      function, both in auxin signaling and pathogen response.
AB  - The tobacco (Nicotiana tabacum) bZIP transcription factor BZI-1 is involved in
      auxin-mediated growth responses and in establishing pathogen defenses. Transgenic
      plants expressing a dominant-negative BZI-1-DeltaN derivative, which lacks the N
      terminal activation domain, showed altered vegetative growth. In particular auxin
      induced rooting and formation of tobacco mosaic virus-induced hypersensitive
      response lesions are affected. BZI-1-related proteins described in various plant
      species share the conserved domains D1, D2, BD, and D4. To define those BZI-1
      domains involved in transcription factor function, BZI-1 deletion derivatives
      were expressed in transgenic plants. The domains D1 or BD are crucial for BZI-1
      DeltaN function in planta. The basic BD domain is mediating DNA binding of BZI-1.
      Yeast two-hybrid and in vitro binding studies reveal the ankyrin-repeat protein
      ANK1, which specifically interacts with a part of the BZI-1 protein (amino acids
      73-222) encoding the D1 domain. ANK1 does not bind DNA or act as a co-activator
      of BZI-1-mediated transcription. Moreover, green fluorescence protein
      localization studies propose that ANK1 is acting mainly inside the cytosol.
      Transcription analysis reveals that ANK1 is ubiquitously expressed, but after
      pathogen attack transcription is transiently down-regulated. Along these lines,
      ANK1 homologous proteins in Arabidopsis thaliana have been reported to function
      in pathogen defense. We therefore propose that the D1 domain serves as an
      interaction surface for ANK1, which appears to regulate BZI-1 function in auxin
      signaling as well as pathogen response.

PMID- 12499373
TI  - In vitro characterization of conditions for amyloid-beta peptide oligomerization
      and fibrillogenesis.
AB  - Extensive research causally links amyloid-beta peptide (A beta) to Alzheimer's
      disease, although the pathologically relevant A beta conformation remains
      unclear. A beta spontaneously aggregates into the fibrils that deposit in senile
      plaques. However, recent in vivo and in vitro reports describe a potent
      biological activity for oligomeric assemblies of A beta. To consistently prepare
      in vitro oligomeric and fibrillar forms of A beta 1-42, a detailed knowledge of
      how solution parameters influence structure is required. This manuscript
      represents the first study using a single chemically and structurally homogeneous
      unaggregated starting material to demonstrate that the formation of oligomers,
      fibrils, and fibrillar aggregates is determined by time, concentration,
      temperature, pH, ionic strength, and A beta species. We recently reported that
      oligomers inhibit neuronal viability 10-fold more than fibrils and approximately
      40-fold more than unaggregated peptide, with oligomeric A beta 1-42-induced
      neurotoxicity significant at 10 nm. In addition, we were able to differentiate by
      structure and neurotoxic activity wild-type A beta1-42 from isoforms containing
      familial mutations (Dahlgren, K. N., Manelli, A. M., Stine, W. B., Jr., Baker, L.
      K., Krafft, G. A., and LaDu, M. J. (2002) J. Biol. Chem. 277, 32046-32053).
      Understanding the biological role of specific A beta conformations may define the
      link between A beta and Alzheimer's disease, re-focusing therapeutic approaches
      by identifying the pernicious species of A beta ultimately responsible for the
      cognitive dysfunction that defines the disease.

PMID- 12499374
TI  - GDP affinity and order state of the catalytic site are critical for function of
      xanthine nucleotide-selective Galphas proteins.
AB  - Xanthine nucleotide-selective small GTP-binding proteins with an Asp/Asn mutation
      are valuable for the analysis of individual GTP-binding proteins in complex
      systems. Similar applications can be devised for heterotrimeric G-proteins.
      However, Asp/Asn mutants of Galpha(o), Galpha(11), and Galpha(16) were inactive.
      An additional Gln/Leu mutation in the catalytic site, reducing GTPase activity
      and increasing GDP affinity, was required to generate xanthine nucleotide
      selective unspecified G-protein alpha-subunit (Galpha). Our study aim was to
      generate xanthine nucleotide-selective mutants of Galpha(s), the stimulatory G
      protein of adenylyl cyclase. The short splice variant of Galpha(s) (Galpha(sS))
      possesses higher GDP affinity than the long splice variant (Galpha(sL)).
      Nucleoside 5'-[gamma-thio]triphosphates (NTPgammaSs) and nucleoside 5'
      [beta,gamma-imido]triphosphates effectively activated a Galpha(sS) mutant with a
      D280N exchange (Galpha(sS)-N280), whereas nucleotides activated a Galpha(sL)
      mutant with a D295N exchange (Galpha(sL)-N295) only weakly. The Gln/Leu mutation
      enhanced Galpha(sL)-N295 activity. NTPgammaSs activated Galpha(sS)-N280 and a
      Galpha(sL) mutant with a Q227L and D295N exchange (Galpha(sL)-L227/N295) with
      similar potencies, whereas xanthosine 5'-triphosphate and xanthosine 5'
      [beta,gamma-imido]triphosphate were more potent than GTP and guanosine 5'
      [beta,gamma-imido]triphosphate, respectively. Galpha(sS)-N280 interacted with the
      beta(2)-adrenoreceptor and exhibited high-affinity XTPase activity. Collectively,
      (i) Galpha(sS)-N280 is the first functional xanthine nucleotide-selective Galpha
      with the Asp/Asn mutation alone; (ii) sufficiently high GDP affinity is crucial
      for Galpha Asp/Asn mutant function; (iii) with nucleoside 5'-triphosphates and
      nucleoside 5'-[beta,gamma-imido]triphosphates, Galpha(s)-N280 and Galpha(sL)
      L227/N295 exhibit xanthine nucleotide selectivity, whereas NTPgammaSs sterically
      perturb the catalytic site of Galpha and annihilate xanthine selectivity.

PMID- 12499375
TI  - Identification of conserved amino acid residues in rat liver carnitine
      palmitoyltransferase I critical for malonyl-CoA inhibition. Mutation of
      methionine 593 abolishes malonyl-CoA inhibition.
AB  - Carnitine palmitoyltransferase (CPT) I, which catalyzes the conversion of
      palmitoyl-CoA to palmitoylcarnitine facilitating its transport through the
      mitochondrial membranes, is inhibited by malonyl-CoA. By using the SequenceSpace
      algorithm program to identify amino acids that participate in malonyl-CoA
      inhibition in all carnitine acyltransferases, we found 5 conserved amino acids
      (Thr(314), Asn(464), Ala(478), Met(593), and Cys(608), rat liver CPT I
      coordinates) common to inhibitable malonyl-CoA acyltransferases (carnitine
      octanoyltransferase and CPT I), and absent in noninhibitable malonyl-CoA
      acyltransferases (CPT II, carnitine acetyltransferase (CAT) and choline
      acetyltransferase (ChAT)). To determine the role of these amino acid residues in
      malonyl-CoA inhibition, we prepared the quintuple mutant CPT I
      T314S/N464D/A478G/M593S/C608A as well as five single mutants CPT I T314S, N464D,
      A478G, M593S, and C608A. In each case the CPT I amino acid selected was mutated
      to that present in the same homologous position in CPT II, CAT, and ChAT. Because
      mutant M593S nearly abolished the sensitivity to malonyl-CoA, two other Met(593)
      mutants were prepared: M593A and M593E. The catalytic efficiency (V(max)/K(m)) of
      CPT I in mutants A478G and C608A and all Met(593) mutants toward carnitine as
      substrate was clearly increased. In those CPT I proteins in which Met(593) had
      been mutated, the malonyl-CoA sensitivity was nearly abolished. Mutations in
      Ala(478), Cys(608), and Thr(314) to their homologous amino acid residues in CPT
      II, CAT, and ChAT caused various decreases in malonyl-CoA sensitivity. Ala(478)
      is located in the structural model of CPT I near the catalytic site and
      participates in the binding of malonyl-CoA in the low affinity site (Morillas,
      M., Gomez-Puertas, P., Rubi, B., Clotet, J., Arino, J., Valencia, A., Hegardt, F.
      G., Serra, D., and Asins, G. (2002) J. Biol. Chem. 277, 11473-11480). Met(593)
      may participate in the interaction of malonyl-CoA in the second affinity site,
      whose location has not been reported.

PMID- 12499376
TI  - The ST6Gal I sialyltransferase selectively modifies N-glycans on CD45 to
      negatively regulate galectin-1-induced CD45 clustering, phosphatase modulation,
      and T cell death.
AB  - The addition of sialic acid to T cell surface glycoproteins influences essential
      T cell functions such as selection in the thymus and homing in the peripheral
      circulation. Sialylation of glycoproteins can be regulated by expression of
      specific sialyltransferases that transfer sialic acid in a specific linkage to
      defined saccharide acceptor substrates and by expression of particular
      glycoproteins bearing saccharide acceptors preferentially recognized by different
      sialyltransferases. Addition of alpha2,6-linked sialic acid to the
      Galbeta1,4GlcNAc sequence, the preferred ligand for galectin-1, inhibits
      recognition of this saccharide ligand by galectin-1. SAalpha2,6Gal sequences,
      created by the ST6Gal I enzyme, are present on medullary thymocytes resistant to
      galectin-1-induced death but not on galectin-1-susceptible cortical thymocytes.
      To determine whether addition of alpha2,6-linked sialic acid to lactosamine
      sequences on T cell glycoproteins inhibits galectin-1 death, we expressed the
      ST6Gal I enzyme in a galectin-1-sensitive murine T cell line. ST6Gal I expression
      reduced galectin-1 binding to the cells and reduced susceptibility of the cells
      to galectin-1-induced cell death. Because the ST6Gal I preferentially utilizes N
      glycans as acceptor substrates, we determined that N-glycans are essential for
      galectin-1-induced T cell death. Expression of the ST6Gal I specifically resulted
      in increased sialylation of N-glycans on CD45, a receptor tyrosine phosphatase
      that is a T cell receptor for galectin-1. ST6Gal I expression abrogated the
      reduction in CD45 tyrosine phosphatase activity that results from galectin-1
      binding. Sialylation of CD45 by the ST6Gal I also prevented galectin-1-induced
      clustering of CD45 on the T cell surface, an initial step in galectin-1 cell
      death. Thus, regulation of glycoprotein sialylation may control susceptibility to
      cell death at specific points during T cell development and peripheral
      activation.

PMID- 12499378
TI  - Functional analysis of TBX5 missense mutations associated with Holt-Oram
      syndrome.
AB  - TBX5 is a T-box transcription factor that plays a critical role in organogenesis.
      Seven missense mutations in TBX5 have been identified in patients with Holt-Oram
      syndrome characterized by congenital heart defects and upper limb abnormalities.
      However, the functional significance and molecular pathogenic mechanisms of these
      mutations are not clear. In this study we describe functional defects in DNA
      binding, transcriptional activity, protein-protein interaction, and cellular
      localization of mutant TBX5 with these missense mutations (Q49K, I54T, G80R,
      G169R, R237Q, R237W, and S252I). Mutations G80R, R237Q, and R237W represent a
      group of mutations that dramatically reduce DNA-binding activity of TBX5, leading
      to reduced transcription activation by TBX5 and the loss of synergy in
      transcriptional activation between TBX5 and NKX2.5. The second group of mutations
      includes Q49K, I54T, G169R, and S252I, which have no or moderate effect on DNA
      binding activity and the function of transcription activation of TBX5 but cause
      the complete loss of synergistic transcription activity between TBX5 and NKX2.5.
      All seven missense mutations greatly reduced the interaction of TBX5 with NKX2.5
      in vivo and in vitro. Immunofluorescent staining showed that wild type TBX5 was
      localized completely into the nucleus, but mutants were localized in both nucleus
      and cytoplasm. These results demonstrate that all seven missense mutations
      studied here are functional mutations with a spectrum of defects ranging from
      decreases in DNA-binding activity and transcriptional activation to the dramatic
      reduction of interaction between TBX5 and NKX2.5, and loss of synergy in
      transcriptional activation between these two proteins, as well as impairment in
      the nuclear localization of TBX5. These defects are likely central to the
      pathogenesis of Holt-Oram syndrome.

PMID- 12499379
TI  - O-glycosylation of mucin-like domain retains the neutral ceramidase on the plasma
      membranes as a type II integral membrane protein.
AB  - Ceramidase is a key enzyme involved in regulating cellular levels of ceramide,
      sphingosine, and possibly sphigosine 1-phosphate and thus could modulate
      sphingolipid signaling. Here we report that O-glycosylation of the mucin-like
      domain of neutral ceramidases was required for localization to the surface of
      plasma membranes. The deduced amino acid sequences of the mammalian enzymes
      contain a serine-threonine-rich domain (mucin box), which follows the
      signal/anchor sequence, whereas those of bacterial and invertebrate enzymes
      completely lack a mucin box, suggesting that the specific domain has been
      acquired during evolution. In HEK293 cells overexpressing ceramidase, the enzyme
      was not only secreted into the medium after cleavage of the NH(2)-terminal
      signal/anchor sequence but also localized at the plasma membrane as a type II
      integral membrane protein. Lectin blot analysis using peanut agglutinin revealed
      that the mucin box of the enzyme is highly glycosylated with O-glycans.
      Interestingly, a mutant lacking the mucin box or possible O-glycosylation sites
      in the mucin box was secreted into the medium but not localized at the surface of
      the cells. Furthermore, a mucin box-fused chimera green fluorescent protein
      (GFP), but not GFP itself, with the signal/anchor sequence was distributed on the
      surface of the cells. These results suggest that O-glycosylation of the mucin box
      retains proteins on the plasma membranes. We also found that the 112-kDa membrane
      bound enzyme from mouse kidney is O-glycosylated, whereas the 94-kDa soluble
      enzyme from liver is not. These results clearly indicate that post-translational
      modification of the enzyme with O-glycans is tissue-specific and helps the enzyme
      to localize at the surface of plasma membranes as a type II membrane protein.

PMID- 12499380
TI  - Association of the death-inducing signaling complex with microdomains after
      triggering through CD95/Fas. Evidence for caspase-8-ganglioside interaction in T
      cells.
AB  - In this investigation we show that the death-inducing signaling complex (DISC)
      associates with glycosphingolipid-enriched microdomains (GEM) upon CD95/Fas
      engagement. We primarily analyzed the ganglioside pattern and composition of GEM
      after triggering through CD95/Fas and observed that GM3 is the main ganglioside
      constituent of GEM. Stimulation with anti-CD95/Fas did not cause translocation of
      gangliosides within or from the GEM fraction. Scanning confocal microscopy showed
      that triggering through CD95/Fas induced a significant GM3-caspase-8 association,
      as revealed by nearly complete colocalization areas. Coimmunoprecipitation
      experiments demonstrated that GM3 and GM1 were immunoprecipitated by anti-caspase
      8 only after triggering through CD95/Fas. This association was supported by the
      recruitment of caspase-8, as well as of CD95/Fas, to GEM upon CD95/Fas
      engagement, as revealed by the analysis of linear sucrose gradient fractions. It
      indicates that the DISC associates with GEM; no changes were observed in the
      distribution of caspase-9. The disruption of GEM by methyl-beta-cyclodextrin
      prevented DNA fragmentation, as well as CD95/Fas clustering on the cell surface,
      demonstrating a role for GEM in initiating of Fas signaling. These findings
      strongly suggest a role for gangliosides as structural components of the membrane
      multimolecular signaling complex involved in CD95/Fas receptor-mediated apoptotic
      pathway.

PMID- 12499381
TI  - Differential regulation of amidase- and formamidase-mediated ammonia production
      by the Helicobacter pylori fur repressor.
AB  - The production of high levels of ammonia allows the human gastric pathogen
      Helicobacter pylori to survive the acidic conditions in the human stomach. H.
      pylori produces ammonia through urease-mediated degradation of urea, but it is
      also able to convert a range of amide substrates into ammonia via its AmiE
      amidase and AmiF formamidase enzymes. Here data are provided that demonstrate
      that the iron-responsive regulatory protein Fur directly and indirectly regulates
      the activity of the two H. pylori amidases. In contrast to other amidase-positive
      bacteria, amidase and formamidase enzyme activities were not induced by medium
      supplementation with their respective substrates, acrylamide and formamide. AmiE
      protein expression and amidase enzyme activity were iron-repressed in H. pylori
      26695 but constitutive in the isogenic fur mutant. This regulation was mediated
      at the transcriptional level via the binding of Fur to the amiE promoter region.
      In contrast, formamidase enzyme activity was not iron-repressed but was
      significantly higher in the fur mutant. This effect was not mediated at the
      transcriptional level, and Fur did not bind to the amiF promoter region. These
      roles of Fur in regulation of the H. pylori amidases suggest that the H. pylori
      Fur regulator may have acquired extra functions to compensate for the absence of
      other regulatory systems.

PMID- 12499382
TI  - Residues involved in the catalysis, base specificity, and cytotoxicity of
      ribonuclease from Rana catesbeiana based upon mutagenesis and X-ray
      crystallography.
AB  - The Rana catesbeiana (bullfrog) ribonucleases, which belong to the RNase A
      superfamily, exert cytotoxicity toward tumor cells. RC-RNase, the most active
      among frog ribonucleases, has a unique base preference for pyrimidine-guanine
      rather than pyrimidine-adenine in RNase A. Residues of RC-RNase involved in base
      specificity and catalytic activity were determined by site-directed mutagenesis,
      k(cat)/K(m) analysis toward dinucleotides, and cleavage site analysis of RNA
      substrate. The results show that Pyr-1 (N-terminal pyroglutamate), Lys-9, and Asn
      38 along with His-10, Lys-35, and His-103 are involved in catalytic activity,
      whereas Pyr-1, Thr-39, Thr-70, Lys-95, and Glu-97 are involved in base
      specificity. The cytotoxicity of RC-RNase is correlated, but not proportional to,
      its catalytic activity. The crystal structure of the RC-RNase.d(ACGA) complex was
      determined at 1.80 A resolution. Residues Lys-9, His-10, Lys-35, and His-103
      interacted directly with catalytic phosphate at the P(1) site, and Lys-9 was
      stabilized by hydrogen bonds contributed by Pyr-1, Tyr-28, and Asn-38. Thr-70
      acts as a hydrogen bond donor for cytosine through Thr-39 and determines B(1)
      base specificity. Interestingly, Pyr-1 along with Lys-95 and Glu-97 form four
      hydrogen bonds with guanine at B(2) site and determine B(2) base specificity.

PMID- 12499383
TI  - Rapid flip-flop of oleic acid across the plasma membrane of adipocytes.
AB  - Nonesterified long-chain fatty acids may enter cells by free diffusion or by
      membrane protein transporters. A requirement for proteins to transport fatty
      acids across the plasma membrane would imply low partitioning of fatty acids into
      the membrane lipids, and/or a slower rate of diffusion (flip-flop) through the
      lipid domains compared to the rates of intracellular metabolism of fatty acids.
      We used both vesicles of the plasma membrane of adipocytes and intact adipocytes
      to study transmembrane fluxes of externally added oleic acid at concentrations
      below its solubility limit at pH 7.4. Binding of oleic acid to the plasma
      membrane was determined by measuring the fluorescent fatty acid-binding protein
      ADIFAB added to the external medium. Changes in internal pH caused by flip-flop
      and metabolism were measured by trapping a fluorescent pH indicator in the cells.
      The metabolic end products of oleic acid were evaluated over the time interval
      required for the return of intracellular pH to its initial value. The primary
      findings were that (i) oleic acid rapidly binds with high avidity in the lipid
      domains of the plasma membrane with an apparent partition coefficient similar to
      that of protein-free phospholipid bilayers; (ii) oleic acid rapidly crosses the
      plasma membrane by the flip-flop mechanism (both events occur within 5 s); and
      (iii) the kinetics of esterification of oleic acid closely follow the time
      dependence of the recovery of intracellular pH. Any postulated transport
      mechanism for facilitating translocation of fatty acid across the plasma membrane
      of adipocytes, including a protein transporter, would have to compete with the
      highly effective flip-flop mechanism.

PMID- 12499384
TI  - Isolation and characterization of androgen receptor mutant, AR(M749L), with
      hypersensitivity to 17-beta estradiol treatment.
AB  - Estrogens, primarily 17beta-estradiol (E(2)), may play important roles in male
      physiology via the androgen receptor (AR). It has already been shown that E(2)
      modulates AR function in LNCaP prostate cancer cells and xenograft CWR22 prostate
      cancer tissues. Using a molecular model of E(2) bound-AR-ligand binding domain
      (LBD) and employing site-directed mutagenesis strategies, we screened several AR
      mutants that were mutated at E(2)-AR contact sites. We found a mutation at amino
      acid 749, AR(M749L), which confers AR hypersensitivity to E(2). The reporter
      assays demonstrate that E(2) can function, like androgen, to induce AR(M749L)
      transactivation. This E(2)-induced AR mutant transactivation is a direct effect
      of the AR(M749L), because the transactivation was blocked by antiandrogens. The
      hypersensitivity of AR(M749L) to E(2) is not due to increased affinity of
      AR(M749L) for E(2), rather it may be due to the existence of the proper
      conformation necessary to maintain E(2) binding to the AR-LBD long enough to
      result in E(2)-induced transactivation. AR(M749L) transactivation can be further
      enhanced in the presence of AR coregulators, such as ARA70 and SRC-1. Therefore,
      amino acid 749 may represent an important site within the AR-LBD that is involved
      in interaction with E(2) that, when mutated, allows E(2) induction of AR
      transactivation.

PMID- 12499385
TI  - Binding and transport in norepinephrine transporters. Real-time, spatially
      resolved analysis in single cells using a fluorescent substrate.
AB  - Monoamine transporters, the molecular targets for drugs of abuse and
      antidepressants, clear norepinephrine, dopamine, or serotonin from the synaptic
      cleft. Neurotransmitters, amphetamines, and neurotoxins bind before being
      transported, whereas cocaine and antidepressants bind to block transport.
      Although binding is crucial to transport, few assays separate binding from
      transport, nor do they provide adequate temporal or spatial resolution to
      describe real-time kinetics or localize sites of active uptake. Here, we report a
      new method that distinguishes substrate binding from substrate transport using
      single-cell, space-resolved, real-time fluorescence microscopy. For these studies
      we use a fluorescent analogue of 1-methyl-4-phenylpyridinium, a neurotoxic
      metabolite and known substrate of monoamine transporters, to assess binding and
      transport with 50-ms, sub-micron resolution. We show that ASP(+) (4-(4
      (dimethylamino)styrl)-N-methylpyridinium) has micromolar potency for the human
      norepinephrine transporter, that ASP(+) accumulation is Na(+)-, Cl(-)-, cocaine-,
      and desipramine-sensitive and temperature-dependent, and that ASP(+) competes
      with norepinephrine uptake. Using this method we demonstrate that norepinephrine
      transporters are efficient buffers for substrate, with binding rates exceeding
      transport rates by 100-fold. Furthermore, substrates bind deep within the
      transporter, isolated from both the bath and the lipid bilayer. Although
      transport per se depends on Na(+) and Cl(-), binding is independent of Na(+) and
      actually increases in low Cl(-). We further demonstrate that ASP(+) interacts
      with transporters not only in transfected cells but in cultured neurons. ASP(+)
      is also a substrate for dopamine and serotonin transporters and therefore
      represents a powerful new technique for studying the biophysical properties of
      monoamine transporters, an approach also amenable to high throughput assays for
      drug discovery.

PMID- 12499386
TI  - Intravacuolar membrane lysis in Saccharomyces cerevisiae. Does vacuolar targeting
      of Cvt17/Aut5p affect its function?
AB  - The integral membrane protein Cvt17/Aut5p is a putative lipase essential for
      intravacuolar lysis of autophagic bodies. It is localized at the endoplasmic
      reticulum, from which it is targeted via the multivesicular body (MVB) pathway to
      intravacuolar MVB vesicles. Proteinase protection experiments now demonstrate
      that the Aut5 amino terminus is located in the cytosol, and the carboxyl terminus
      is located inside the ER lumen. In contrast to procarboxypeptidase S, targeting
      of Cvt17/Aut5p to MVB vesicles is not blocked in cells lacking the ubiquitin
      ligase Tul1p or the deubiquitinating enzyme Doa4p. Also, truncation of the amino
      terminal cytosolic Cvt17/Aut5p domain does not inhibit its targeting to MVB
      vesicles. These findings suggest that similar to Sna3p sorting of Cvt17/Aut5p to
      MVB vesicles is independent of ubiquitination. By fusing the ER
      retention/retrieval signal HDEL to the carboxyl terminus of Cvt17/Aut5p, we
      generated a construct that is held back at the ER. Detailed analysis of this
      construct suggests an essential role of vacuolar targeting of Cvt17/Aut5p for its
      function. Consistently, aut5Delta cells are found impaired in vacuolar
      degradation of autophagocytosed peroxisomes. Importantly, biochemical and
      morphological data further suggest involvement of Cvt17/Aut5p in disintegration
      of intravacuolar MVB vesicles. This points to a general function of Cvt17/Aut5p
      in intravacuolar membrane breakdown.

PMID- 12499387
TI  - T cell receptor can be recruited to a subset of plasma membrane rafts,
      independently of cell signaling and attendantly to raft clustering.
AB  - The constitutive/inducible association of the T cell receptor (TCR) with isolated
      detergent-resistant, lipid raft-derived membranes has been studied in Jurkat T
      lymphocytes. Membranes resistant to 1% Triton X-100 contained virtually no
      CD3epsilon, part of the TCR complex, irrespective of cell stimulation. On the
      other hand, membranes resistant either to a lower Triton X-100 concentration
      (i.e. 0.2%) or to the less hydrophobic detergent Brij 58 (1%) contained (i) a low
      CD3epsilon amount (approximate 2.7% of total) in resting cells and (ii) a several
      times higher amount of the TCR component, after T cell stimulation with either
      antigen-presenting cells or with phytohemagglutinin. It appeared that CD3/TCR was
      constitutively associated with and recruited to a raft-derived membrane subset
      because (i) all three membrane preparations contained a similar amount of the
      raft marker tyrosine kinase Lck but no detectable amounts of the conventional
      membrane markers, CD45 phosphatase and transferrin receptor; (ii) a larger amount
      of particulate membranes were resistant to solubilization with 0.2% Triton X-100
      and Brij 58 than to solubilization with 1% Triton X-100; and (iii) higher
      cholesterol levels were present in membranes resistant to either the lower Triton
      X-100 concentration or to Brij 58, as compared with those resistant to 1% Triton
      X-100. The recruitment of CD3 to the raft-derived membrane subset appeared (i) to
      occur independently of cell signaling events, such as protein-tyrosine
      phosphorylation and Ca(2+) mobilization/influx, and (ii) to be associated with
      clustering of plasma membrane rafts induced by multiple cross-linking of either
      TCR or the raft component, ganglioside GM(1). We suggest that during T cell
      stimulation a lateral reorganization of rafts into polarized larger domains can
      determine the recruitment of TCR into these domains, which favors a polarization
      of the signaling cascade.

PMID- 12499388
TI  - Lipid raft-dependent and -independent signaling through HLA-DR molecules.
AB  - Lipid rafts are plasma membrane microdomains that are highly enriched in
      signaling molecules and that act as signal transduction platforms for many immune
      receptors. The involvement of these microdomains in HLA-DR-induced signaling is
      less well defined. We examined the constitutive presence of HLA-DR molecules in
      lipid rafts, their possible recruitment into these microdomains, and the role of
      these microdomains in HLA-DR-induced responses. We detected significant amounts
      of HLA-DR molecules in the lipid rafts of EBV(+) and EBV(-) B cell lines,
      monocytic cell lines, transfected HeLa cells, tonsillar B cells, and human
      monocytes. Localization of HLA-DR in these microdomains was unaffected by the
      deletion of the cytoplasmic domain of both the alpha and beta chains. Ligation of
      HLA-DR with a bivalent, but not a monovalent, ligand resulted in rapid tyrosine
      phosphorylation of many substrates, especially Lyn, and activation of ERK1/2 MAP
      kinase. However, the treatment failed to induce further recruitment of HLA-DR
      molecules into lipid rafts. The HLA-DR-induced signaling events were accompanied
      by the induction of cell-cell adhesion that could be inhibited by PTK and Lyn but
      not ERK1/2 inhibitors. Disruption of lipid rafts by methyl-beta-cyclodextrin
      (MbetaCD) resulted in the loss of membrane raft association with HLA-DR
      molecules, inhibition of HLA-DR-mediated protein tyrosine phosphorylation and
      cell-cell adhesion. MbetaCD did not affect the activation of ERK1/2, which was
      absent from lipid rafts. These results indicate that although all the HLA-DR
      induced events studied are dependent on HLA-DR dimerization, some require the
      presence of HLA-DR molecules in lipid rafts, whereas others do not.

PMID- 12499389
TI  - Mapping CD55 function. The structure of two pathogen-binding domains at 1.7 A.
AB  - Decay-accelerating factor (CD55), a regulator of the alternative and classical
      pathways of complement activation, is expressed on all serum-exposed cells. It is
      used by pathogens, including many enteroviruses and uropathogenic Escherichia
      coli, as a receptor prior to infection. We describe the x-ray structure of a
      pathogen-binding fragment of human CD55 at 1.7 A resolution containing two of the
      three domains required for regulation of human complement. We have used
      mutagenesis to map biological functions onto the molecule; decay-accelerating
      activity maps to a single face of the molecule, whereas bacterial and viral
      pathogens recognize a variety of different sites on CD55.

PMID- 12499390
TI  - Disruption of scribble (Scrb1) causes severe neural tube defects in the
      circletail mouse.
AB  - Circletail is one of only two mouse mutants that exhibit the most severe form of
      neural tube defect (NTD), termed craniorachischisis. In this disorder, almost the
      entire brain and spinal cord is affected, owing to a failure to initiate neural
      tube closure. Craniorachischisis is a significant cause of lethality in humans,
      yet the molecular mechanisms involved remain poorly understood. Here, we report
      the identification of the gene mutated in circletail (Crc), using a positional
      cloning approach. This gene, Scrb1, encodes a member of the LAP protein family
      related to Drosophila scribble, with 16 leucine rich repeats and four PDZ
      domains. The Crc mutant contains a single base insertion that creates a frame
      shift and leads to premature termination of the Scrb1 protein. We report the
      expression pattern of Scrb1 during embryonic and fetal development, and show that
      Scrb1 expression closely mirrors the phenotypic defects observed in Crc/Crc
      mutants. In addition, circletail genetically interacts with the loop-tail mutant,
      and we reveal overlapping expression of Scrb1 with Vangl2, the gene mutated in
      loop-tail. The identification of the Crc gene further defines the nature of the
      genetic pathway required for the initiation of neural tube closure and provides
      an important new candidate that may be implicated in the aetiology of human NTDs.

PMID- 12499391
TI  - Nonsense mediated decay downregulates conserved alternatively spliced ABCC4
      transcripts bearing nonsense codons.
AB  - Drug transporters are an important part of the defense of cells against cytotoxic
      agents. One major group of transporters is known as multidrug resistance
      associated proteins (MRP; ABCC gene family). The MRPs belong to the ATP binding
      cassette transporter superfamily. One family member, ABCC4 (also known as MRP4)
      functions as a cellular efflux pump for anti-HIV drugs, such as 9-(2
      phoshoenylmethoxyethyl) adenine and azido-thymidine-monophosphate, an antiviral
      nucleotide, ganciclovir-monophosphate, and anti-cancer agents such as
      thiopurines. We isolated a ABCC4 cDNA encoding a non-functional protein, owing to
      an insertion, and subsequently determined the ABCC4 gene structure. This analysis
      revealed that the insertion was attributed to two additional exons that would be
      predicted to produce premature termination codons (PTC) in ABCC4. The highly
      similar mouse Abcc4 gene also contained these exons, which were remarkable
      because their size and sequence identity were much higher than the overall
      similarity between these genes. Further, a comparison of human, monkey and rodent
      ABCC4 genes revealed that these same PTC-producing exons were also highly
      conserved in evolution. As all the ABCC4 mRNA containing these PTC exons might
      produce nonsense mRNA, we further tested the hypothesis that these mRNAs were
      targets of nonsense-mediated mRNA decay (NMD). Protein synthesis inhibition
      selectively stabilized PTC containing ABCC4 transcripts in human, monkey and
      rodent cell lines. Moreover, the amount of PTC-containing ABCC4 transcripts was
      critically dependent upon protein synthesis, as removal of the inhibitor
      dramatically decreased expression, which correlated with the resumption of
      protein synthesis. These are the first studies to indicate that the highly
      conserved PTC exons of the ABCC4 gene may dictate its expression.

PMID- 12499392
TI  - Haplotype analysis of the CETP gene: not TaqIB, but the closely linked -629C-->A
      polymorphism and a novel promoter variant are independently associated with CETP
      concentration.
AB  - The TaqIB polymorphism in intron 1 of the cholesteryl ester transfer protein
      (CETP) gene is associated with plasma CETP concentration, high-density
      lipoprotein cholesterol (HDL-C) and coronary artery disease (CAD). These
      associations are generally thought to arise from linkage disequilibrium between
      TaqIB and (an)other functional polymorphism(s). To identify putative functional
      sites, we investigated phenotypic associations of TaqIB and four tightly linked
      polymorphisms (novel -2708G-->A and +784CCC-->A, and previously identified -971G-
      >A and -629C-->A) in 709 males with CAD (REGRESS). In addition to genotype
      analyses, a novel method to estimate haplotype effects was used to examine the
      individual and joint effects of these DNA variants on CETP concentration and HDL
      C. All polymorphisms were associated with CETP concentration and HDL-C, except
      for -971 with HDL-C. Stepwise regression and haplotype analyses indicated that
      only -629 was independently associated with HDL-C. Similar analyses additionally
      indicated that -2708 and -629 were independently associated with CETP
      concentration, whereby the most frequent alleles acted in a cumulative manner.
      Nonetheless, detailed haplotype analysis revealed that a 3-polymorphism haplotype
      model consisting of -2708, -629 and -971 explained the variation in CETP
      concentration best. The involvement of -971 could be due to interaction effects
      that were observed between -971 and both -629 (P<0.001) and -2708 (P=0.047). In
      conclusion, the TaqIB polymorphism is not instrumental in determining CETP or HDL
      C levels, but is a marker for the -629 promoter variant. Our analyses,
      furthermore, indicate that the -2708 and -971 polymorphisms are likely to play a
      role in determining CETP concentration.

PMID- 12499393
TI  - Characterization and quantitation of differential Tsix transcripts: implications
      for Tsix function.
AB  - In dosage compensation of female mammals, the accumulation of Xist RNA initiates
      silencing of one X-chromosome. Xist action is repressed by the antisense gene,
      Tsix, whose full-length RNA product is complementary to Xist RNA in mice. While
      previous work showed that Tsix transcription blocks the accumulation of Xist RNA,
      it is still unclear whether this repression requires the antisense RNA product or
      whether the antisense transcriptional movement is sufficient. A better
      understanding of potential mechanisms requires elucidation of Tsix RNA structure
      and determination of Tsix RNA copy number relative to that of Xist RNA. Previous
      work indicated that at least some of murine Tsix is spliced and that human TSIX
      truncates within the 3' end of XIST. Here, further characterization and
      quantitation of murine Tsix RNA reveal three new findings: first, in
      undifferentiated embryonic stem cells, Tsix RNA is present at 10-100-fold molar
      excess over Xist RNA. Second, only 30-60% of Tsix RNA is spliced at known exon
      intron junctions. The nearly equal abundance of spliced and unspliced species
      leaves open possible roles for both isoforms. Finally, Tsix is spliced
      heterogeneously at the 5' end and most detectable splice variants exhibit only a
      1.9 kb region of complementarity between sense and antisense RNAs. Implications
      for Tsix's possible mechanisms of action are discussed.

PMID- 12499394
TI  - Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by
      homozygosity-by-descent mapping in a large Hutterite pedigree.
AB  - Serum triglyceride (TG) level is a well-known risk factor for cardiovascular
      disease, a leading cause of morbidity and mortality in Western countries.
      Although genome-wide scans for TG have been conducted in several populations, few
      loci have shown strong evidence for linkage. The Hutterites are a founder
      population, which practices a communal lifestyle that includes a uniformly high
      fat, high-cholesterol diet. We measured serum TG in 485 Hutterites >or=14 years
      old and performed a genome-wide scan to find genetic determinants of the observed
      variation in TG levels, using mapping methods that take advantage of the
      extensive inbreeding and linkage disequilibrium (LD) in this single, 1623-member
      pedigree. We report two highly significant associations with TG levels, alleles
      at D2S410 on 2q14 (locus P=5.8 x 10(-6), genome-wide P=0.005) and at IFNA on
      chromosome 9p21 (locus P=4.3 x 10(-5), genome-wide P=0.024). In each case,
      homozygosity at the locus is associated with low TG levels, suggesting that
      alleles at nearby loci may protect against high TG levels.

PMID- 12499395
TI  - Intracellular retention is a common characteristic of childhood obesity
      associated MC4R mutations.
AB  - Heterozygous mutations in the coding region of the serpentine Melanocortin 4
      receptor are the most common genetic cause of human obesity described to date.
      There are still conflicting data regarding the overall prevalence of such
      mutations in obesity and limited information is available on the functional
      defects caused by most obesity-associated MC4R mutations. We report here the
      screening for mutations in the coding region of the MC4R of a new cohort of 172
      patients presenting with severe childhood obesity and a family history of
      obesity. Three heterozygous MC4R mutations (Ser127Leu, Ala244Glu and Pro299His)
      were found in three patients of this cohort (1.74%), confirming that such
      mutations are implicated in a significant number of childhood obesity cases. A
      functional analysis of these mutant receptors, in addition to 11 other childhood
      obesity-associated MC4R mutations, indicates that they all alter the activation
      of the receptor by the endogenous agonist alpha-MSH. To further examine the
      functional defects caused by childhood obesity-associated MC4R mutations, we
      developed a novel, sensitive technique to quantitatively analyze the effect of a
      mutation on MC4R cell surface expression. Using this method we analyzed the cell
      surface expression of all the 14 described childhood obesity-associated MC4R
      missense mutations. We demonstrate that 81.3% of childhood obesity-associated
      heterozygous MC4R mutations lead to intracellular retention of the receptor. This
      result has implications for the potential pharmacologic rescue of childhood
      obesity-associated MC4R mutations and for the treatment of patients presenting
      with this condition.

PMID- 12499396
TI  - Interaction of alphaPIX (ARHGEF6) with beta-parvin (PARVB) suggests an
      involvement of alphaPIX in integrin-mediated signaling.
AB  - Members of the Rho GTPase family are key regulatory molecules that link surface
      receptors to the organization of the actin cytoskeleton. It is now well
      established that these small GTPases are also crucial for neuronal morphogenesis
      and connectivity. Moreover, mutations in ARHGEF6 (also known as alphaPIX or Cool
      2 ), encoding a Rac1/Cdc42-specific guanine nucleotide exchange factor, have been
      implicated in X-linked mental retardation. In an attempt to get insight into the
      biological function of ARHGEF6 and the upstream signaling cascades leading to its
      activation, we used the full-length coding region of ARHGEF6 as bait in yeast-two
      hybrid screens and identified PARVB (beta-parvin or affixin) as a novel binding
      partner. The interaction was confirmed by co-immunoprecipitation and GST pull
      down. We showed by immunofluorescence that ARHGEF6 and PARVB co-localize at the
      cell periphery to lamellipodia and ruffles in well-spread and actively spreading
      cells adhered to fibronectin. In addition, interaction of ARHGEF6 to ARHGEF7
      (betaPIX or Cool-1), a close homolog of ARHGEF6, was confirmed. In in vivo
      assays, two ARHGEF6 mutations identified previously in patients with X-linked non
      specific mental retardation, ARHGEF6 deltaaa56-83 and deltaaa396-776, abolished
      interaction of ARHGEF6 to PARVB. Binding between ARHGEF6 and ARHGEF7 was not
      affected by ARHGEF6 deltaaa56-83 but did not occur with ARHGEF6 deltaaa396-776.
      These data suggest that both the N-terminal calponin homology (CH) and C-terminal
      coiled-coil domains are necessary for the ARHGEF6-PARVB binding. In contrast, it
      seems that only the coiled-coil domain is required for the interaction and
      heterodimerization of ARHGEF6 and ARHGEF7. PARVB is known to interact with
      integrin-linked kinase (ILK) and is involved in the early stage of cell-substrate
      interaction through integrins. The identification of PARVB as an ARHGEF6
      interacting partner together with the co-localization of ARHGEF6 and ILK in
      spreading cells suggest that ARHGEF6 is involved in integrin-mediated signaling
      leading to activation of the GTPases Rac1 and/or Cdc42.

PMID- 12499397
TI  - Human BOULE gene rescues meiotic defects in infertile flies.
AB  - Defects in human germ cell development are common and yet little is known of
      genes required for germ cell development in men and women. The pathways that
      develop germ cells appear to be conserved broadly, at least in outline, in
      organisms as diverse as flies and humans beginning with allocation of cells to
      the germ cell lineage, migration of these cells to the fetal gonad, mitotic
      proliferation and meiosis of the germ cells, and maturation into sperm and eggs.
      In model organisms, a few thousand genes may be required for germ cell
      development including meiosis. To date, however, no genes that regulate critical
      steps of reproduction have been shown to be functionally conserved from flies to
      humans. This may be due in part to strong selective pressures that are thought to
      drive reproductive genes to high degrees of divergence. Here, we investigated the
      micro- and macro-evolution of the BOULE gene, a member of the human DAZ (deleted
      in azoospermia) gene family, within primates, within mammals and within
      metazoans. We report that sequence divergence of BOULE is unexpectedly low and
      that rapid evolution is not detectable. We extend the evolutionary analysis of
      BOULE to the level of phyla and show that a human BOULE transgene can advance
      meiosis in infertile boule mutant flies. This is the first demonstration that a
      human reproductive gene can rescue reproductive defects in a fly. These studies
      lend strong support to the idea that BOULE may encode a key conserved switch that
      regulates progression of germ cells through meiosis in men.

PMID- 12499398
TI  - A central role of interferon regulatory factor-1 for the limitation of neointimal
      hyperplasia.
AB  - Neointima formation, the leading cause of restenosis after catheter angioplasty,
      is a paradigm for vascular proliferative responses. Neointima formation is self
      limiting after a variable degree of tissue growth, causing significant
      renarrowing in a substantial number of patients. To investigate the mechanisms
      that limit neointima formation we studied the role of the transcription factor
      IRF-1, which is a regulator of interferons and a tumor suppressor. We demonstrate
      that IRF-1 is highly regulated in human vascular lesions and exhibits a growth
      inhibitory function in coronary artery smooth muscle cells (CASMC). IRF-1
      deficient mice display a high grade of susceptibility towards neointima formation
      following vessel injury. IRF-1 leads to G(1) cell cycle arrest in CASMC and
      induces the CDK inhibitor p21. In addition, IRF-1 induces NO production, which is
      known to attenuate endothelial dysfunction. Mitogen-mediated cellular migration
      is abrogated by IRF-1. In conclusion, IRF-1 displays pleiotropic anti-restenotic
      activities in vascular restenosis through transcriptional activation of several
      relevant mechanisms that limit neointima formation. These findings suggest an
      important role of this transcription factor as an endogenous inhibitor of
      neointimal growth following vessel injury and it is likely that IRF-1 regulation
      also plays a role in the pathophysiology of primary atherosclerosis. In addition,
      IRF-1 may be an interesting target for interventions to prevent neointimal
      hyperplasia.

PMID- 12499399
TI  - Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links
      actin filaments and controls sarcomere assembly.
AB  - The assembly and maintenance of the muscle sarcomere requires a complex interplay
      of actin- and myosin-associated proteins. Myotilin is a thin filament-associated
      Z-disc protein that consists of two Ig-domains flanked by a unique serine-rich
      amino-terminus and a short carboxy-terminal tail. It binds to alpha-actinin and
      filamin c and is mutated in limb girdle muscular dystrophy 1A (LGMD1A). Here we
      show that myotilin also directly binds F-actin, efficiently cross-links actin
      filaments alone or in concert with alpha-actinin and prevents filament
      disassembly induced by Latrunculin A. Myotilin forms dimers via its carboxy
      terminal half, which may be necessary for the actin-bundling activity.
      Overexpression of full-length myotilin but not the carboxy-terminal half induces
      formation of thick actin cables in non-muscle cells devoid of endogenous
      myotilin. The expression of myotilin in muscle cells is tightly regulated to the
      later stages of in vitro myofibrillogenesis, when preassembled myofibrils begin
      to align. Expression of either amino- or carboxy-terminally truncated myotilin
      fragments but not wild-type myotilin in differentiating myocytes leads to
      myofibril disarray. The disease association and functional characteristics
      indicate an indispensable role for myotilin in stabilization and anchorage of
      thin filaments, which may be a prerequisite for correct Z-disc organization.

PMID- 12499400
TI  - A complete alpha1,3-galactosyltransferase gene is present in the human genome and
      partially transcribed.
AB  - The synthesis of Galalpha1-3Gal-terminated oligosaccharides (alpha-Gal) epitopes
      has been interrupted during the course of evolution, starting with Old World
      primates. Partial sequences similar to the alpha1,3-galactosyltransferase
      (alpha1,3GalT) gene, which governs the synthesis of alpha-Gal epitopes, have been
      detected in the human genome and were found to correspond to pseudogenes. We
      completed the sequence of the human alpha1,3GalT pseudogene present on chromosome
      9 and found it to be organized like the murine alpha1,3GalT gene. In human cell
      lines and several normal and tumor tissues we detected truncated transcripts
      corresponding to this pseudogene. Considering these mRNAs, translation of an open
      reading frame containing the first four translated exons but missing the two
      catalytic exons could predict a truncated alpha1,3GalT polypeptide that should be
      enzymatically inactive. We show that transcription of human alpha1,3GalT is
      prematurely terminated at the level of a strong transcriptional stop signal in
      the middle of intron VII. We were able to reproduce this effect in vitro by
      subcloning the implicated DNA region upstream from a reporter cDNA. The premature
      transcriptional arrest of human alpha1,3-GalT gene leads to an ectopic splicing
      event and to the connection of a short intronic sequence downstream from
      translated exons. Finally, we show that these truncated transcripts are
      overexpressed in cell lines with modifications of O-glycans.

PMID- 12499401
TI  - Histidine 271 has a functional role in pig alpha-1,3galactosyltransferase enzyme
      activity.
AB  - Alpha(1,3)Galactosyltransferase (GT) is a Golgi-localized enzyme that catalyzes
      the transfer of a terminal galactose to N-acetyllactosamine to create
      Galalpha(1,3)Gal. This glycosyltransferase has been studied extensively because
      the Galalpha(1,3)Gal epitope is involved in hyperacute rejection of pig-to-human
      xenotransplants. The original crystal structure of bovine GT defines the amino
      acids forming the catalytic pocket; however, those directly involved in the
      interaction with the donor nucleotide sugars were not characterized. Comparison
      of amino acid sequences of GT from several species with the human A and B
      transferases suggest that His271 of pig GT may be critical for recognition of the
      donor substrate, UDP-Gal. Using pig GT as the representative member of the GT
      family, we show that replacement of His271 with Ala, Leu, or Gly caused complete
      loss of function, in contrast to replacement with Arg, another basic charged
      residue, which did not alter the ability of GT to produce Galalpha(1,3)Gal.
      Molecular modeling showed that His271 may interact directly with the Gal moiety
      of UDP-Gal, an interaction possibly retained by replacing His with Arg. However,
      replacing His271 with amino acids found in alpha(1,3)GalNAc transferases did not
      change the donor nucleotide specificity. Thus His271 is critical for enzymatic
      function of pig GT.

PMID- 12499402
TI  - Glycopeptide export from the endoplasmic reticulum into cytosol is mediated by a
      mechanism distinct from that for export of misfolded glycoprotein.
AB  - When glycoproteins formed in the endoplasmic reticulum (ER) are misfolded, they
      are generally translocated into the cytosol for ubiquitination and are
      subsequently degraded by the proteasome. This system, the so-called ER-associated
      glycoprotein degradation, is important for eukaryotes to maintain the quality of
      glycoproteins generated in the ER. It has been established in yeast that several
      distinct proteins are involved in this translocation and degradation processes.
      Small glycopeptides formed in the ER are exported to the cytosol in a similar
      manner. This glycopeptide export system is conserved from yeast to mammalian
      cells, suggesting its basic biological significance for eukaryotic cells. These
      two export systems (for misfolded glycoproteins and glycopeptides) share some
      properties, such as a requirement for ATP and involvement of Sec61p, a central
      membrane protein presumably forming a dislocon channel for export of proteins.
      However, the machinery of glycopeptide export is poorly understood. In this
      study, various mutants known to have an effect on export/degradation of misfolded
      glycoproteins were examined for glycopeptide export activity with a newly
      established assay method. Surprisingly, most of the mutants were found not to
      exhibit a defect in glycopeptide export. The only gene that was found to be
      required on efficient export of both types of substrates was PMR1, the gene
      encoding the medial-Golgi Ca(2+)/Mn(2+)-ion pump. These results provide evidence
      that although the systems involved in export of misfolded glycoproteins and
      glycopeptides share some properties, they have exhibited distinct differences.

PMID- 12499403
TI  - Identification, cloning, purification, and enzymatic characterization of
      Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate synthase.
AB  - The enzyme encoded by Rv2682c in Mycobacterium tuberculosis is a functional 1
      deoxy-D-xylulose 5-phosphate synthase (DXS), suggesting that the pathogen
      utilizes the mevalonate-independent pathway for isopentenyl diphosphate and
      subsequent polyprenyl phosphate synthesis. These key precursors are vital in the
      biosynthesis of many essential aspects of the mycobacterial cell wall. Rv2682c
      encodes the conserved DRAG sequence that has been proposed as a signature motif
      for DXSs and also all 13 conserved amino acid residues thought to be important to
      the function of transketolase enzymes. Recombinant Rv2682c is capable of
      utilizing glyceraldehyde 3-phosphate and erythrose 4-phosphate as well as D- and
      L-glyceraldehyde as aldose substrates. The enzyme has K(m) values of 40 microM,
      6.1 microM, 5.6 mM, and 4.5 mM for pyruvate, D-glyceraldehyde 3-phosphate, D
      glyceraldehyde, and L-glyceradehyde, respectively. Rv2682c has an absolute
      requirement for divalent cation and thiamin diphosphate as cofactors. The K(d)
      (thiamin diphosphate )for the native M. tuberculosis DXS activity partially
      purified from M. tuberculosis cytosol is 1 microM in the presence of Mg(2+).

PMID- 12499404
TI  - Production in yeast of alpha-galactosidase A, a lysosomal enzyme applicable to
      enzyme replacement therapy for Fabry disease.
AB  - A mammalian-like sugar moiety was created in glycoprotein by Saccharomyces
      cerevisiae in combination with bacterial alpha-mannosidase to produce a more
      economic enzyme replacement therapy for patients with Fabry disease. We
      introduced the human alpha-galactosidase A (alpha-GalA) gene into an S.
      cerevisiae mutant that was deficient in the outer chains of N-linked mannan. The
      recombinant alpha-GalA contained both neutral (Man(8)GlcNAc(2)) and acidic ([Man
      P](1-2)Man(8)GlcNAc(2)) sugar chains. Because an efficient incorporation of alpha
      GalA into lysosomes of human cells requires mannose-6-phosphate (Man-6-P)
      residues that should be recognized by the specific receptor, we trimmed down the
      sugar chains of the alpha-GalA by a newly isolated bacterial alpha-mannosidase.
      Treatment of the alpha-GalA with the alpha-mannosidase resulted in the exposure
      of a Man-6-P residue on a nonreduced end of oligosaccharide chains after the
      removal of phosphodiester-linked nonreduced-end mannose. The treated alpha-GalA
      was efficiently incorporated into fibroblasts derived from patients with Fabry
      disease. The uptake was three to four times higher than that of the nontreated
      alpha-GalA and was inhibited by the addition of 5 mM Man-6-P. Incorporated alpha
      GalA was targeted to the lysosome, and hydrolyzed ceramide trihexoside
      accumulated in the Fabry fibroblasts after 5 days. This method provides an
      effective and economic therapy for many lysosomal disorders, including Fabry
      disease.

PMID- 12499405
TI  - An investigation of the interactions of E-selectin with fuco-oligosaccharides of
      the blood group family.
AB  - This investigation is concerned with assignments of Lewis(a) (Le(a)) and Le(x)
      analogs on linear and branched di- to hexasaccharide backbones as components of
      the recognition motifs for E-selectin. The influence of the location of fucose
      residue(s) was investigated using 14 structurally defined and variously
      fucosylated oligosaccharides in biotinylated form or as neoglycolipids in static
      binding assays, in microwells, and on thin-layer chromatograms. Results of the
      two assay systems were in agreement overall and showed that the recognition
      motifs for E-selectin include 4-fucosyl-lacto (Le(a)) and 3-fucosyl-neo-lacto
      (Le(x)) sequences strictly at capping positions and not Le(x) at an internal
      position as a part of VIM-2 antigen sequence. There is greater potency of the
      Le(a) over the Le(x) series. Additional fucose residues alpha1-2-linked to
      neighboring galactoses or alpha1-3-linked to inner N-acetyglucosamines or to
      reducing-terminal glucose residues of the tetrasaccharide backbone had little or
      no effect on the selectin binding. E-selectin binding to the Le(a) or Le(x
      )capping motif on a 3-linked branch was equivalent to the binding on the
      corresponding linear backbone. A lack of E-selectin binding to the Le(x) motif
      capping a 6-linked branch and to the Le(x) trisaccharide linked to biotin via a
      nine-carbon spacer indicates that the -GlcNAcbeta1-3Gal- sequence on the
      oligosaccharide backbone adjoining the Le(x) is a part of recognition motif for E
      selectin. These findings contribute to understanding the molecular basis of E
      selectin recognition and could influence future designs of selectin antagonists
      as possible therapeutic substances.

PMID- 12499406
TI  - Identification of glycan structure and glycosylation sites in cellobiohydrolase
      II and endoglucanases I and II from Trichoderma reesei.
AB  - Mass spectrometric techniques combined with enzymatic digestions were applied to
      determine the glycosylation profiles of cellobiohydrolase (CBH II) and
      endoglucanases (EG I, II) purified from filamentous fungus Trichoderma reesei.
      Electrospray mass spectrometry (ESMS) analyses of the intact cellulases revealed
      the microheterogeneity in glycosylation where glycoforms were spaced by hexose
      units. These analyses indicated that glycosylation accounted for 12-24% of the
      molecular mass and that microheterogeneity in both N- and O-linked glycans was
      observed for each glycoprotein. The identification of N-linked attachment sites
      was carried out by MALDI-TOF and capillary liquid chromatography-ESMS analyses of
      tryptic digests from each purified cellulase component with and without PNGase F
      incubation. Potential tryptic glycopeptide candidates were first detected by
      stepped orifice-voltage scanning and the glycan structure and attachment site
      were confirmed by tandem mass spectrometry. For purified CBH II, 74% of glycans
      found on Asn310 were high mannose, predominantly Hex(7-9)GlcNAc(2), whereas the
      remaining amount was single GlcNAc; Asn289 had 18% single GlcNAc occupancy, and
      Asn14 remained unoccupied. EG I presented N-linked glycans at two out of the six
      potential sites. The Asn56 contained a single GlcNAc residue, and Asn182 showed
      primarily a high-mannose glycan Hex(8)GlcNAc(2) with only 8% being occupied with
      a single GlcNAc. Finally, EG II presented a single GlcNAc residue at Asn103. It
      is noteworthy that the presence of a single GlcNAc in all cellulase enzymes
      investigated and the variability in site occupancy suggest the secretion of an
      endogenous endo H enzyme in cultures of T. reesei.

PMID- 12499407
TI  - Expression of histo-blood group A antigen increases resistance to apoptosis and
      facilitates escape from immune control of rat colon carcinoma cells.
AB  - A and B histo-blood group antigens are present on carcinoma cells at the early
      stages of cancerogenesis and tend to disappear at later stages, but it is not yet
      clear whether they take part to the process of tumor progression. To gain some
      insight into this issue, we used a rat colon carcinoma experimental model. To
      obtain expression of the A antigen, REG cells were cotransfected with the rat A
      enzyme cDNA and a rat alpha1,2fucosyltransferase cDNA, either FTA or FTB, whereas
      PRO cells that spontaneously have alpha1,2fucosyltransferase activity were only
      transfected with the A enzyme cDNA. All A antigen-expressing transfected cells
      derived from either REG FTA, REG FTB, or PRO parental cells were more resistant
      to apoptosis induced by either serum deprivation or heat shock than were their
      respective controls. When injected to syngeneic immunocompetent rats, A enzyme
      transfected PRO cells formed tumors that grew faster than those formed by mock
      transfected PRO cells. However, in immunodeficient SCID mice, no difference in
      growth could be observed between the two types of tumors, indicating that the
      faster tumor growth of the A antigen-positive cells in immunocompetent animals
      was due to their higher ability to escape immune control and that this was
      associated with their higher degree of resistance to apoptosis. These results
      might explain the slightly augmented incidence of carcinomas observed in A and B
      blood group individuals compared to O individuals.

PMID- 12499408
TI  - Functional neuroimaging studies of patients.

PMID- 12499409
TI  - Functional imaging studies of neuropsychological patients: applications and
      limitations.
AB  - Functional imaging studies of neuropsychologically impaired patients have not
      enjoyed the immediate success that was attained by functional imaging studies of
      normal subjects. This is largely because it has taken time to appreciate some of
      the deeper issues surrounding study design, analysis and interpretation. The most
      significant limitation is that functional imaging experiments with patients need
      tasks that the patients can perform. This precludes direct investigations of the
      physiological correlates of cognitive deficits. Nevertheless, functional imaging
      studies of brain-damaged patients who retain task competence can provide
      information that is not available from structural imaging, behavioural
      assessments or functional imaging with normal subjects. This is because intact
      task performance, following a brain lesion, does not necessarily entail normal
      neuronal responses in undamaged cortical areas. Abnormal neuronal responses, in
      the context of normal performance, can indicate alternative neuronal and
      cognitive mechanisms for supporting the same task. This, in turn, has important
      implications for understanding the mechanisms that mediate recovery and the
      organizational principles that underlie functional architectures in the human
      brain.

PMID- 12499410
TI  - Investigating cognitive neuroplasticity in single cases: lessons learned from
      applying functional neuroimaging techniques to the traditional neuropsychological
      case study framework.
AB  - We summarize two case studies as a context for discussing the use of neuroimaging
      as a convergent methodology in the study of neuroplasticity in single subjects.
      Throughout this paper we argue for a different approach for including
      neuroimaging in these types of study. Previous case studies of neuroplasticity in
      patients (ours as well as others reported elsewhere) have added neuroimaging to
      the traditional neuropsychological framework of comparing patient results with
      matched control groups, and synthesized results through descriptions of
      anatomical and behavioral dissociations. This type of approach is referred to as
      the comparison approach. We advocate a different approach that builds on findings
      from previous behavioral skill learning research. Specifically, we propose adding
      neuroimaging throughout learning or recovery of the ability of interest and
      making inferences from systematic changes in activation topography and intensity
      that occur within the context of predicted behavioral changes. We dub this
      approach the online approach. This approach should allow future investigators to
      circumvent many of the interpretation pitfalls that are common in comparison
      studies.

PMID- 12499411
TI  - Cerebral organization in a right-handed trilingual patient with right-hemisphere
      speech: a positron emission tomography study.
AB  - Using the method of positron emission tomography, combined with word-generation
      tasks, we had the opportunity to examine the cerebral representation of multiple
      languages in the brain in a right-handed patient, RA, with known right-hemisphere
      speech representation as determined by intracarotid sodium amobarbital testing.
      Similar patterns of cerebral blood flow were observed across all three languages
      (French, Spanish and English), when synonym generation was compared with a silent
      resting baseline. In particular, several regions in the right inferior frontal
      cortex were activated. These foci are in locations corresponding to those
      observed in the left hemisphere in normal right-handed volunteers with presumed
      left-hemisphere dominance, and in patients known to be left-hemisphere dominant
      for speech. The lack of anatomical separation of the three languages within the
      same individual, who acquired two languages early and one language later in life,
      suggests that at least at this single-word level of analysis, age of acquisition
      was not a significant factor in the determining of functional organization in the
      brain.

PMID- 12499412
TI  - Recovery of semantic word processing in transcortical sensory aphasia: a
      functional magnetic resonance imaging study.
AB  - In a previous functional magnetic resonance imaging (fMRI) study with normal
      subjects, we demonstrated regions related to conceptual-semantic word processing
      around the first frontal sulcus (BA 9) and the posterior parietal lobe (BA 7/40)
      in agreement with several previous reports. We had the possibility, using the
      same fMRI paradigm, to study two consecutive cases with left middle cerebral
      artery (MCA) infarction (RC and HP) and lesions affecting either solely the pre
      frontal (HP) or both the pre-frontal and posterior parietal part of the network
      activated in normal subjects (RC). Both patients showed transcortical sensory
      aphasia (TSA) on acute assessment. This contradicts classical disconnection
      accounts of the syndrome stating intact conceptual representations in TSA. Their
      recovery of language comprehension was associated with activation of a left
      hemispheric network. Mainly activations of left perilesional pre-frontal regions
      (RC), left Wernicke's area (RC and HP) or the left posterior middle and inferior
      temporal cortex (HP) were demonstrated in the TSA patients. The latter findings
      suggest that in our cases of TSA functional take-over has occurred in regions
      with related functions ('redundancy recovery') rather than in previously
      unrelated areas ('vicarious functioning'). Our data support distributed models of
      conceptual-semantic word processing and multiple left hemispheric representations
      of closely related functions.

PMID- 12499413
TI  - Neural correlates of conscious and unconscious vision in parietal extinction.
AB  - Brain areas activated by stimuli in the left visual field of a right parietal
      patient suffering from left visual extinction were identified using event-related
      functional magnetic resonance imaging. Left visual field stimuli that were
      extinguished from awareness still activated the ventral visual cortex, including
      areas in the damaged right hemisphere. An extinguished face stimulus on the left
      produced robust category-specific activation of the right fusiform face area. On
      trials where the left visual stimulus was consciously seen rather than
      extinguished, greater activity was found in the ventral visual cortex of the
      damaged hemisphere, and also in frontal and parietal areas of the intact
      hemisphere. These findings extend recent observations on visual extinction,
      suggesting distinct neural correlates for conscious and unconscious perception.

PMID- 12499414
TI  - Detecting residual cognitive function in persistent vegetative state.
AB  - Despite converging agreement about the definition of persistent vegetative state,
      recent reports have raised concerns about the accuracy of diagnosis in some
      patients, and the extent to which, in a selection of cases, residual cognitive
      functions may remain undetected. Objective assessment of residual cognitive
      function can be extremely difficult as motor responses may be minimal,
      inconsistent, and difficult to document in many patients, or may be undetectable
      in others because no cognitive output is possible. Here we describe strategies
      for using H(2)(15)O positron emission tomography activation studies to study
      covert cognitive processing in patients with a clinical diagnosis of persistent
      vegetative state. Three cases are described in detail. Of these, two exhibited
      clear and predicted regional cerebral blood flow responses during well-documented
      activation paradigms (face recognition and speech perception) which have been
      shown to produce specific, robust and reproducible activation patterns in normal
      volunteers. Some months after scanning, both patients made a significant
      recovery. In a third case, blood flow data were acquired during a speech
      perception task, although methodological difficulties precluded any systematic
      interpretation of the results. In spite of the multiple logistic and procedural
      problems involved, these results have major clinical and scientific implications
      and provide a strong basis for the systematic study of possible residual
      cognitive function in patients diagnosed as being in a persistent vegetative
      state.

PMID- 12499415
TI  - High dose rate endobronchial brachytherapy effectively palliates symptoms due to
      inoperable lung cancer.
AB  - BACKGROUND: Intraluminal brachytherapy has become an established treatment for
      major airway occlusion by relapsed or persistent inoperable endobronchial tumors.
      The aim of this study was to compare the palliation improvement pre- and post
      radiotherapy. METHODS: The study group was 95 patients with the diagnosis of
      inoperable lung cancer who were eligible for HDR brachytherapy. Fiber-optic
      bronchoscopy was performed and the level and degree of endobronchial obstruction
      were estimated in terms of bronchial obstruction index. Endobronchial irradiation
      was delivered using remote HDR afterloading brachytherapy with iridium-192.
      Brachytherapy was delivered at weeks 1, 2 and 3 at 7.5 Gy per fraction or at
      weeks 1 and 2 at 10 Gy per fraction. All patients were evaluated at the beginning
      and at the third month of therapy. Using Speiser's symptomatic scoring criteria,
      the severity of symptoms (dyspnea, cough, hemoptysis and postobstructive
      pneumonia) was weighted. Bronchoscopic findings at the initial evaluation and at
      the third month were also scored. Surviving patients were followed up for a
      minimum of 3 months with a mean of 7.5 +/- 5.35 months (median: 6 months).
      RESULTS: All the symptoms and bronchial obstruction improved significantly after
      brachytherapy (P < 0.05). The most responding symptoms were dyspnea and
      hemoptysis. The factors determining the complete response were evaluated; age,
      staging, histological type, lesion localization and previous history of
      radiotherapy did not seem to determine the complete response (P > 0.05).
      CONCLUSIONS: All the symptoms and bronchial obstruction index seemed to improve
      after brachytherapy. However, it is difficult to predict the response before the
      therapy.

PMID- 12499416
TI  - Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell
      lung cancer: a phase II study.
AB  - PURPOSE: To assess the activity and toxicity of low-dose weekly paclitaxel in
      patients with non-resectable or metastatic non-small cell lung cancer (NSCLC) and
      who had disease recurrence or failure with previous chemotherapy. PATIENTS AND
      METHODS: Forty patients with NSCLC previously treated with platinum-based
      chemotherapy received weekly paclitaxel 80 mg/m(2) as a 1 h infusion. The median
      age was 63 years (range 42-77 years); 25 patients had Eastern Cooperative
      Oncology Group performance status (PS) 1 and 15 had PS 2. Thirty-one patients had
      stage IV disease and nine stage III (eight stage IIIB and one stage IIIA).
      RESULTS: A total of 364 weeks of treatment were administered (median 8 weeks,
      range 2-17 weeks). There were no episodes of grade 3 or 4 haematological
      toxicities. Severe non-haematological toxicity was uncommon: grade 1-2 asthenia
      in 50%; grade 1-2 motor neuropathy in 45% and grade 3 in 10%; grade 1-2 sensory
      neuropathy in 62% of patients. Alopecia was mild. The overall response rate was
      37.5% (95% CI, 23.9-55): 2 CR, 13 PR, 15 SD, 8 PD, 2 NE. Median overall survival
      was 9.7 months (95% CI, 6.5-12.8). Median time to progression was 5.4 months (95%
      CI, 1.8-8.9). CONCLUSION: A low-dose weekly paclitaxel regimen had good clinical
      efficacy with low toxicity in this group of patients with poor prognosis. This
      regimen increases the therapeutic options available for second-line therapy in
      NSCLC patients.

PMID- 12499417
TI  - Prognostic factors in patients with hepatocellular carcinoma treated by
      transcatheter arterial embolization.
AB  - BACKGROUND: Transcatheter arterial embolization induces marked antitumor response
      in patients with hepatocellular carcinoma, but the survival benefit of
      transcatheter arterial embolization remains to be determined. This study
      investigated prognostic factors in patients with advanced hepatocellular
      carcinoma treated by transcatheter arterial embolization. METHODS: A total of 128
      consecutive patients with non-resectable hepatocellular carcinoma, who had
      undergone transcatheter arterial embolization between May 1990 and August 1998,
      were analyzed to investigate prognostic factors. RESULTS: Median survival time
      and survival proportions at 1, 3 and 5 years were 3.3 years, 92.0, 54.6 and
      23.4%, respectively. By multivariate analysis using the accelerated failure time
      model, age <60 years, hepatitis C virus antibody positivity, serum albumin >3.5
      g/dl, absence of portal vein invasion and serum alpha-fetoprotein level <400
      ng/ml were significantly associated with favorable survival. For clinical
      application, we also propose a prognostic equation with combination of specific
      prognostic factors, by which survival curves of each patient could be predicted
      directly. CONCLUSION: The findings of the current study may be helpful in
      predicting the life expectancy of hepatocellular carcinoma patients treated by
      transcatheter arterial embolization and in designing future clinical trials of
      transcatheter arterial embolization for hepatocellular carcinoma.

PMID- 12499418
TI  - Clinical study of G3 superficial bladder cancer without concomitant CIS treated
      with conservative therapy.
AB  - OBJECTIVE: The treatment for superficial G3 transitional cell carcinoma (TCC) of
      the urinary bladder remains controversial. It is important to reveal the clinical
      features of superficial G3 bladder cancer that can be treated conservatively.
      PATIENTS AND METHODS: A total of 39 patients with primary superficial bladder
      cancer (Ta, T1) with G3 components but without concomitant carcinoma in situ
      (CIS), who had been treated initially with transurethral resection (TUR), were
      retrospectively analyzed for factors related to tumor recurrence, progression and
      survival. The patients were 34 males and five females whose age ranged from 49 to
      85 years (average, 68 years). Initial tumor stages were Ta in one patient and T1
      in 38. Initial treatments were TUR alone in 18 patients and TUR with adjuvant
      therapy (intravesical chemotherapy or BCG therapy) in 21. Factors examined
      included age, gender, morphology, size and number of tumors and adjuvant
      therapies. RESULTS: Follow-up periods were 3-138 months (median, 37 months).
      Tumor recurrence, progression and cancer death were observed in 23, seven and
      four cases, respectively. The 5-year progression-free rate (75%) and survival
      rate (83%) in 39 patients with G3 did not show a statistically significant
      difference from those of the 109 patients with G1 or the 187 patients with G2
      superficial bladder cancer who were treated with TUR initially. Only the rate of
      recurrence of patients with G3 was significantly higher than that of patients
      with G2 or G1. Adjuvant therapies reduced the recurrence rate of the patients
      with G3. Only tumor morphology, papillary or non-papillary, affected both the
      progression-free rate and the survival rate of patients with G3. There were no
      statistically significant differences associated with other factors. CONCLUSION:
      The results suggest that superficial G3 bladder cancer could be treated with TUR
      initially, especially for papillary tumors.

PMID- 12499419
TI  - Salvage external beam radiotherapy for local recurrence without systemic
      progression or prostate specific antigen recurrence of prostate cancer after
      initial hormonal therapy: is it possible to identify patients likely to have good
      treatment outcomes?
AB  - BACKGROUND: We attempted to identify factors that predict the outcomes of salvage
      external beam radiotherapy (sEBRT) in patients who showed local recurrence
      without systemic progression or isolated prostate specific antigen (PSA)
      recurrence after initial hormonal therapy. METHODS: The subjects were 33 patients
      who were diagnosed as having local recurrence without systemic progression (30
      cases) or isolated PSA recurrence (three cases). Of these patients, those with
      continuously decreasing PSA levels, which were 1.0 ng/ml or less 1-1.5 years
      after sEBRT, were regarded as good responders (GR) whereas the remaining patients
      were regarded as poor responders (nGR). Survival rates in these patients and
      factors that distinguish GR from nGR were evaluated retrospectively. RESULTS: The
      cancer-specific 10-year survival rate was 82.4% in the 33 patients, 100% in the
      21 GR patients and 55% in the 12 nGR patients (P < 0.0001). Stepwise variable
      selection to discriminate between GR and nGR revealed that the time from sEBRT
      initiation to the nadir PSA was the most significant factor (P = 0.000097).
      Before sEBRT, GR can be predicted in patients with pre-sEBRT PSA <30.0 ng/ml and
      PSA doubling time (PSADT) >7.0 months, with a sensitivity of 95.2% (20/21), a
      specificity of 100% and an accuracy of 97.0%. CONCLUSION: Good responses to sEBRT
      can be expected in patients with local recurrence without systemic progression or
      isolated PSA recurrence after initial hormonal therapy when the patients show
      both pre-sEBRT PSA <30.0 ng/ml and PSADT >7.0 months.

PMID- 12499420
TI  - Lectin-reactive alpha-fetoprotein (AFP-L3%) curability and prediction of clinical
      course after treatment of non-seminomatous germ cell tumors.
AB  - OBJECTIVE: Alpha-fetoprotein (AFP) is an important tumor marker for non
      seminomatous germ cell tumors (NSGCTs) that greatly affects diagnosis and the
      evaluations of therapy and therapeutic policy. However, it is sometimes very
      difficult to make the distinction between tumors and falsely elevated AFP levels
      due to benign liver disease. We assessed the usefulness of lectin-reactive alpha
      fetoprotein (AFP-L3%), which has been reported to be superior to total AFP in
      both sensitivity and specificity in hepatocellular carcinomas, for the evaluation
      of predictions of clinical courses after the treatment of NSGCTs. METHODS: Frozen
      sera of 25 tumor-bearing patients with testicular cancers whose AFP levels were
      5.0 ng/ml or higher were used. The total AFP levels and the ratio of L3 fraction
      to total AFP (AFP-L3%) were measured by liquid-phase binding assay (LBA).
      RESULTS: The total AFP levels were 6.3-14 907 ng/ml (median: 105.9 ng/ml). The
      median AFP-L3% was 69.9% (range;: 1.1-88.1%). Except for one patient, 24 patients
      (96.0%) with evident disease showed high levels of AFP-L3% of >50%, regardless of
      their total AFP levels. In nine patients whose sera were sequentially measured,
      AFP-L3% was considered highly useful for the detection of residual tumors (n = 2)
      and recurrence (n = 1) and for the exclusion of false-positive cases (n = 1).
      CONCLUSIONS: When the total AFP level increases slightly (e.g. to 5-20 ng/ml), a
      measurement of AFP-L3% may provide additional useful information for monitoring
      NSGCT patients and in distinguishing falsely elevated AFP.

PMID- 12499421
TI  - Amifostine-induced toxic epidermal necrolysis during radiotherapy: a case report.
AB  - Amifostine is a phosphorylated aminothiol prodrug that can selectively protect
      normal tissues against the toxic effects of chemotherapy and radiotherapy. In
      clinical use amifostine is well tolerated and may rarely cause allergic
      reactions. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are two closely related entities that present with severe acute mucocutaneous
      reactions most often triggered by drugs. There are only two case reports related
      to the use of amifostine during radiotherapy, one case with SJS and the other
      with SJS-TEN overlap. In this paper, a case with amifostine-induced TEN during
      radiotherapy is presented.

PMID- 12499422
TI  - Giant metastatic myxoid liposarcoma causing cardiac tamponade: a case report.
AB  - We report a case of a rapidly progressing isolated giant metastatic myxoid
      liposarcoma to the heart in a 54-year-old man, who presented with acute symptoms
      of cardiac tamponade. Surgery remains the best treatment option for this rare
      condition.

PMID- 12499423
TI  - Poly(ADP-ribose) polymerase and cancer: in relation to the lectures presented by
      Dr Gilbert de Murcia.

PMID- 12499424
TI  - Diagnostic role of tests for T cell receptor (TCR) genes.
AB  - Rapid advances in molecular biological techniques have made it possible to study
      disease pathogenesis at a genomic level. T cell receptor (TCR) gene rearrangement
      is an important event in T cell ontogeny that enables T cells to recognise
      antigens specifically, and any dysregulation in this complex yet highly regulated
      process may result in disease. Using techniques such as Southern blot
      hybridisation, polymerase chain reaction, and flow cytometry it has been possible
      to characterise T cell proliferations in malignancy and in diseases where T cells
      have been implicated in the pathogenesis. The main aim of this article is to
      discuss briefly the process of TCR gene rearrangement and highlight the disorders
      in which expansions or clonal proliferations of T cells have been recognised. It
      will also describe various methods that are currently used to study T cell
      populations in body fluids and tissue, their diagnostic role, and current
      limitations of the methodology.

PMID- 12499426
TI  - What is Good's syndrome? Immunological abnormalities in patients with thymoma.

PMID- 12499428
TI  - Comparative genomic hybridisation divides retinoblastomas into a high and a low
      level chromosomal instability group.
AB  - BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood
      and is responsible for approximately 1% of all deaths caused by childhood cancer.
      AIMS/METHODS: Comparative genomic hybridisation was performed on 13 consecutive,
      histologically confirmed retinoblastomas to analyse patterns of chromosomal
      changes and correlate these to clinicopathological variables. Six cases were
      hereditary and seven cases were sporadic. RESULTS: In 11 of the 13 tumours
      chromosomal abnormalities were detected, most frequently gains. Frequent
      chromosomal gains concerned 6p (46%), 1q (38%), 2p, 9q (30%), 5p, 7q, 10q, 17q,
      and 20q (23%). Frequent losses occurred at Xq (46%), 13q14, 16q, and 4q (23%).
      High level copy number gains were found at 5p15 and 6p11-12. A loss at 13q14
      occurred in three cases only. Relatively few events occurred in the hereditary
      cases (27) compared with the non-hereditary cases (70 events). The number of
      chromosomal aberrations in these 13 retinoblastomas showed a bimodal
      distribution. Seven tumours showed less than four chromosomal aberrations,
      falling into a low level chromosomal instability (CIN) group, and six tumours
      showed at least eight aberrations, falling into a high level CIN group. In the
      low level CIN group the mean age was half that seen in the high level CIN group,
      there were less male patients, and there were more hereditary and bilateral
      cases. Microsatellite instability was not detected in either of the two groups.
      CONCLUSION: Despite the complex pattern of genetic changes in retinoblastomas,
      certain chromosomal regions appear to be affected preferentially. On the basis of
      the number of genetic events, retinoblastomas can be divided in low and a high
      level chromosomal instability groups, which have striking differences in clinical
      presentation.

PMID- 12499427
TI  - acp Best Practice No 168. The investigation and management of obesity.
AB  - Obesity is a chronic condition characterised by an excess of body fat. It is a
      complex disorder of appetite regulation and energy metabolism controlled by
      specific biological factors. In the past 10 years, great progress has been made
      in the scientific understanding of the pathophysiology of obesity and the
      interactions between genetic predisposition to weight gain and the environment.
      This article will review the current understanding of the pathophysiology and the
      approach to the investigation and management of obesity.

PMID- 12499429
TI  - Detection of telomerase, its components, and human papillomavirus in cervical
      scrapings as a tool for triage in women with cervical dysplasia.
AB  - AIM: To examine whether the detection of either telomerase and its components or
      high risk human papillomavirus (HPV) are of value in predicting the presence of
      cervical intraepithelial neoplasia (CIN) grade II/III in women referred because
      of cervical cytology reports showing at most moderate dyskaryosis. METHODS:
      Cervical scrapings of 50 women referred with cytological borderline, mild, or
      moderate dyskaryosis were analysed. Telomerase activity was assessed by a
      commercially available telomere repeat amplification protocol assay and its
      components human telomerase RNA (hTR) and human telomerase reverse transcriptase
      (hTERT) were assessed by reverse transcriptase polymerase chain reaction (PCR).
      HPV was detected by GP5+/6+ PCR enzyme immunosassay. Histological findings on
      colposcopy guided biopsies or excised cervical tissue were regarded as the final
      pathological diagnosis. The sensitivity and specificity for detecting CIN II/III
      were calculated. RESULTS: Twenty eight women were diagnosed with CIN II/III.
      Telomerase activity was detected in none, hTR in 88%, hTERT in 23%, and high risk
      HPV was detected in 79% of these women. As a diagnostic test none of the
      described analyses combined a sensitivity of at least 90% with a specificity >or=
      90%. Despite the small numbers, calculation of the 95% confidence intervals
      excluded a combined sensitivity and specificity of at least 90% for all of the
      evaluated parameters. CONCLUSIONS: Neither detection of telomerase or its
      components, nor detection of high risk HPV seem suitable for the triage of women
      with borderline, mild, and moderate cytological dyskaryosis.

PMID- 12499432
TI  - Corridor consultations and the medical microbiological record: is patient safety
      at risk?
AB  - The performance procedures of the General Medical Council are aimed at
      identifying seriously deficient performance in a doctor. The performance
      procedures require the medical record to be of a standard that enables the next
      doctor seeing the patient to give adequate care based on the available
      information. Setting standards for microbiological record keeping has proved
      difficult. Over one fifth of practising medical microbiologists (including
      virologists) in the UK (139 of 676) responded to a survey undertaken by the
      working group developing the performance procedures for microbiology, to identify
      current practice and to develop recommendations for agreement within the
      profession about the standards of the microbiological record. The cumulative
      frequency for the surveyed recording methods used indicated that at various times
      65% (90 of 139) of respondents used a daybook, 62% (86 of 139) used the back of
      the clinical request card, 57% (79 of 139) used a computer record, and 22% (30 of
      139) used an index card system to record microbiological advice, suggesting wide
      variability in relation to how medical microbiologists maintain clinical records.

PMID- 12499431
TI  - Chromosomal translocation t(11;18)(q21;q21) in gastrointestinal mucosa associated
      lymphoid tissue lymphoma.
AB  - AIMS: To evaluate the chromosomal translocation t(11;18)(q21;q21) in
      gastrointestinal lymphomas. METHODS: A possible API2-MLT fusion transcript
      specific to t(11;18)(q21;q21) was examined by means of reverse transcription
      polymerase chain reaction (RT-PCR) in tumours from 47 cases of primary
      gastrointestinal lymphoma (28 low grade mucosa associated lymphoid tissue (MALT)
      lymphomas, four low grade MALT lymphomas with a high grade component, nine
      secondary diffuse large B cell lymphomas, four primary diffuse large B cell
      lymphomas, and two T cell lymphomas). RESULTS: API2-MLT fusion was seen in four
      of 28 cases of low grade MALT lymphoma, but it was not seen in other types of
      lymphoma. Among the low grade MALT lymphomas, the fusion transcript was seen more
      frequently in colonic tumours than in gastric tumours (two of three compared with
      two of 24) and in tumours with submucosal invasion than in those confined to the
      mucosa (four of 13 compared with 0 of 15). Helicobacter pylori negative tumours
      tended to show a higher positive rate than H pylori positive tumours (three of
      six compared with one of 21). None of the gastric tumours that responded to H
      pylori eradication expressed the API2-MLT fusion transcript. CONCLUSIONS:
      t(11;18)(q21;q21) seems to be one of the genetic alterations related to the
      development of gastrointestinal low grade MALT lymphoma. Such translocations may
      be predominantly associated with the development of intestinal MALT lymphoma.

PMID- 12499433
TI  - A systematic review of outcome measures reported for the therapeutic
      effectiveness of oral anticoagulation.
AB  - AIMS: To evaluate the evidence of therapeutic international normalised ratio
      (INR) control reporting and to provide recommendations for future reporting,
      particularly for research and audit purposes. METHODS: A systematic review of
      literature published over a five year period describing therapeutic INR control.
      Papers were identified from the Medline electronic database, and those that met
      the quality criteria were reviewed independently by an academic general
      practitioner and a consultant haematologist. RESULTS: Fifteen papers were
      identified that met the quality criteria for review. The sample size of studies
      ranged from 53 to 2545 (mean, 483.9) patients. Follow up ranged from three months
      to 13 years. Twelve studies reported results from secondary care only, one from
      primary care only, and two from both primary and secondary care. Seven of the 15
      papers reported percentage time in range, five of 15 papers reported mean INR,
      six of 15 papers reported the proportion of tests in range, and five of 15 papers
      reported mean warfarin dose. Additional methods of presenting INR results were:
      dose changes each month, distribution of INR results, deviation of INR value from
      mean, percentage dose changes, time between visits, and median INR value. Six
      papers reported only one outcome measure, six reported two outcomes, two papers
      reported three outcomes, and one paper reported five outcomes. CONCLUSIONS: It is
      recommended that at least two outcome measures should be reported and measures
      should be selected so that both the INR determinations and dosing advice are
      monitored.

PMID- 12499437
TI  - p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies
      and ThinPrep smears.
AB  - AIM: To examine the potential of p16(INK4A) as a biomarker for dysplastic
      squamous and glandular cells of the cervix in tissue sections and ThinPrep
      smears. METHODS: Immunocytochemical analysis of p16(INK4A) expression was
      performed on 22 normal cervical tissue samples, five cervical glandular
      intraepithelial neoplasia (cGIN), 38 cervical intraepithelial neoplasia 1 (CIN1),
      33 CIN2, 46 CIN3, and 10 invasive cancer cases (eight squamous and two
      adenocarcinomas). All samples were formalin fixed and paraffin wax embedded, and
      immunohistochemical analysis was carried out using a mouse monoclonal anti
      p16(INK4A) antibody after antigen unmasking. The staining intensity was assessed
      using a 0 to 3 scoring system. In addition, the expression status of p16(INK4A)
      was examined in 12 normal ThinPrep smears, one smear exhibiting cGIN, and a total
      of 20 smears exhibiting mild, moderate, and severe dyskaryosis. Human
      papillomavirus (HPV) detection was carried out using a modified SYBR green assay
      system. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were
      used for specific HPV typing. RESULTS: p16(INK4A) immunoreactivity was absent in
      all normal cervical tissues examined. Dysplastic squamous and glandular cells
      were positive for p16(INK4A) expression in all cases included in this study,
      except for one CIN3 case. p16(INK4A) expression was mainly nuclear in CIN1 cases,
      and both nuclear and cytoplasmic in CIN2, CIN3, cGIN, and invasive cases. All
      cases positive for HPV expressed the p16(INK4A) protein, although not all cases
      found positive for p16(INK4A) were HPV positive. In general, the p16(INK4A)
      staining intensity was lower in cases negative for HPV or those containing a low
      risk HPV type. CONCLUSION: This pattern of overexpression demonstrates the
      potential use of p16(INK4A) as a diagnostic marker for cervical squamous and also
      glandular neoplastic lesions. In addition, the technique can be used to identify
      individual dyskaryotic cells in ThinPrep smears. Thus, p16(INK4A) is a useful
      marker of cervical dyskaryosis.

PMID- 12499435
TI  - Endothelin B receptor gene hypermethylation in prostate adenocarcinoma.
AB  - BACKGROUND: Alterations in the methylation patterns of promoter CpG islands have
      been associated with the transcriptional inhibition of genes in many human
      cancers. These epigenetic alterations could be used as molecular markers for the
      early detection of cancer-that is, while potentially curable according to current
      therapeutic strategies. In prostate cancer, GSTP1 hypermethylation is the most
      common epigenetic alteration, and can be detected in up to 90% of cases. Thus,
      screening for methylation of other loci would probably increase the number of
      primary tumours amenable to screening. Moreover, previous studies have shown that
      the endothelin B receptor (EDNRB) gene is abnormally methylated in a high
      proportion of prostate tumours ( approximately 70%). AIMS: To investigate the
      potential use of EDNRB gene hypermethylation as a prostate cancer specific
      marker. METHODS: Methylation specific polymerase chain reaction (MSP) for the
      promoter region of EDNRB was performed on prospectively collected tissue samples
      from 48 patients harbouring clinically localised prostate cancer, and in a group
      of 23 patients with benign prostatic hyperplasia (BPH). Genomic DNA was isolated
      from the samples and the methylation status was examined in a blinded manner.
      RESULTS: EDNRB methylation was found in 40 of 48 of the adenocarcinomas. However,
      the same alteration was found in the paired normal tissue, and 21 of 23 of the
      BPH samples were found to harbour EDNRB hypermethylation. CONCLUSIONS: EDNRB
      hypermethylation at CpG sites upstream of the transcription start site can be
      detected in a high proportion of prostate adenocarcinomas. However, because this
      same alteration is also present in normal and hyperplastic tissue, it does not
      distinguish normal from neoplastic prostate cells, thus precluding its use as a
      prostate cancer marker.

PMID- 12499438
TI  - Clinical, biochemical, and immunohistochemical features of necrobiotic
      xanthogranulomatosis.
AB  - AIMS: To describe the clinical features of two patients with paraproteinaemia and
      necrobiotic xanthogranulomatosis together with detailed immunohistochemistry of
      the lesions in one. METHODS: The clinical history and results of biochemical
      investigations of the patients were retrieved from the files.
      Immunohistochemistry was used to investigate the expression of macrophage and
      mast cell markers, amyloid A and P, S-100 protein, and apolipoprotein AI and B in
      xanthogranulomatous skin lesions from patient 2. In addition, protein A-sepharose
      chromatography was used to separate serum from patient 2 and apolipoprotein B and
      the IgG paraprotein were measured in the fractions eluted. RESULTS:
      Monocytes/macrophages comprised the major cellular component of the lesion, and
      unusually for xanthomata, areas of collagen necrosis were also seen. Activated
      mast cells were present at the margins of macrophage clusters and adjacent to
      areas of collagen necrosis. Serum paraprotein was bound to low density
      lipoproteins as judged by protein A-sepharose chromatography, and was also
      located within macrophagic foam cells of the lesion on immunohistochemistry.
      CONCLUSIONS: These observations demonstrate many features similar to
      atherosclerosis including collagen necrosis and mast cell activation.

PMID- 12499442
TI  - Sputum cytology: an unsatisfactory test?

PMID- 12499439
TI  - APC mutation and tumour budding in colorectal cancer.
AB  - AIM: To determine the frequency of tumour budding and somatic APC mutation in a
      series of colorectal cancers stratified according to DNA microsatellite
      instability (MSI) status. MATERIAL/METHODS: Ninety five colorectal cancers were
      genotyped for APC mutation in the mutation cluster region (exon 15) and scored
      for the presence of tumour budding at the invasive margin in haematoxylin and
      eosin stained sections. A subset was immunostained for beta catenin and p16.
      RESULTS: The frequency of both somatic APC mutation and tumour budding increased
      pari passu in cancers stratified as sporadic MSI high (MSI-H), hereditary non
      polyposis colorectal cancer (HNPCC), MSI low (MSI-L), and microsatellite stable
      (MSS). Both budding and APC mutation were significantly less frequent in sporadic
      MSI-H cancers than in MSI-L or MSS cancers. Tumour buds were characterised by
      increased immunostaining for both beta catenin and p16. CONCLUSION: Tumour
      budding is associated with an adverse prognosis. The lack of budding in MSI-H
      colorectal cancer may account for the improved prognosis of this subset and may
      be explained by an intact WNT signalling pathway and/or inactivated p16(INK4a).

PMID- 12499440
TI  - Low grade marginal zone B cell lymphoma of the breast associated with localised
      amyloidosis and corpora amylacea in a woman with long standing primary Sjogren's
      syndrome.
AB  - Primary low grade marginal zone B cell lymphoma (MZL) of the breast and localised
      mammary amyloidosis are exceedingly rare entities. This report describes the case
      of a woman with long standing Sjogren's syndrome presenting with asymptomatic MZL
      of the breast showing plasmacytic differentiation, associated with local ductular
      amyloidosis. The lesion was discovered incidentally in breast tissue resected for
      microcalcifications. Immunohistochemistry revealed kappa light chain restriction,
      supporting the neoplastic nature of the infiltrate. A retrospective molecular
      study of the salivary gland biopsy showed a B cell clone. This is the first
      report of the association of human mammary ductular amyloidosis with cartwheel
      shaped material identical to corpora amylacea, usually seen in brain, lung, and
      prostate, but unknown in the human breast. The excellent outcome without
      treatment seen in this patient further emphasises the need to distinguish between
      MZL with plasmacytic differentiation and extramedullary plasmacytoma.

PMID- 12499443
TI  - A rare presentation of a rare disease.

PMID- 12499444
TI  - CD10 is useful in demonstrating endometrial stroma at ectopic sites and in
      confirming a diagnosis of endometriosis.

PMID- 12499445
TI  - Glottis oedema and interstitial pulmonary disease as a result of extramedullary
      haemopoiesis in polycythaemia vera rubra causing asphyctic death.

PMID- 12499447
TI  - Detection of genes with tissue-specific expression patterns using Akaike's
      information criterion procedure.
AB  - We applied a method based on Akaike's information criterion (AIC) to detect genes
      whose expression profile is considerably different in some tissue(s) than in
      others. Such observations are detected as outliers, and the method we used was
      originally developed to detect outliers. The main advantage of the method is that
      objective decisions are possible because the procedure is independent of a
      significance level. We applied the method to 48 expression ratios corresponding
      to various tissues in each of 14,610 clones obtained from the RIKEN Expression
      Array Database (READ; http://read.gsc.riken.go.jp). As a result, for several
      tissues (e.g., muscle, heart, and tongue tissues that contain similar cell types)
      we objectively obtained specific clones without any "thresholding." Our study
      demonstrates the feasibility of the method for detecting tissue-specific gene
      expression patterns.

PMID- 12499446
TI  - Neurokinin 1 receptors and neprilysin modulation of mouse bladder gene
      regulation.
AB  - Neurokinin 1 (NK(1)) receptors play a fundamental role in neurogenic
      inflammation. We sought to determine the mechanisms downstream from NK(1)
      receptor (NK(1)R) activation using cDNA arrays and a novel statistical method to
      analyze gene expression. We used female NK(1)R(-/-) and wild-type (WT) mice that
      were sensitized actively by intraperitoneal injections of dinitrophenol 4
      (DNP(4))-human serum albumin. Cystitis was induced by intravesical instillation
      of antigen of DNP(4)-ovalbumin, and control mice were challenged with saline. At
      1, 4, and 24 h after instillation, bladders were removed for 1) RNA extraction (n
      = 3), 2) replicate of RNA extraction (n = 3), and 3) morphological analysis (n =
      6). For cDNA array experiments, three bladders from each group were homogenized,
      and total RNA was obtained. DNase-treated RNA was reverse-transcribed to cDNA,
      labeled with [alpha-(32)P]dATP and hybridized to Atlas Mouse 1.2 Arrays
      (Clontech). After calculating the mean and SD for background spots, each
      experimental value was assigned a normalized score S using the formula S' = (S -
      Av)/SD, where S' is the original pixel value, and Av and SD are the mean and
      standard deviation of background spots, respectively. Only genes that expressed 3
      SD values above background were used. Hypervariable genes were sorted by cluster
      analysis. Matrices of correlation coefficients were calculated and represented in
      a connectivity mosaic. As results, we found that in WT mice the most prominent
      gene cluster had neprilysin in a central position and positively correlated to a
      group of activator protein-1 (AP-1)-responsive genes, including laminin-alpha3,
      tissue plasminogen activator 11, fos-B, and TNF-beta. In WT mice, antigen-induced
      bladder inflammation led to a downregulation in neprilysin expression. In
      contrast, NK(1)R(-/-) mice failed to mount an inflammatory reaction and presented
      neprilysin negatively correlated with the same genes described in WT. In
      conclusion, this work indicates an overriding participation of NK(1)R and
      neprilysin in bladder inflammation, provides a working model for the involvement
      of AP-1 transcription factor, and evokes testable hypotheses regarding the role
      of NK(1)R and neprilysin in inflammation.

PMID- 12499448
TI  - Good medical practice for occupational physicians.

PMID- 12499449
TI  - Reducing work related psychological ill health and sickness absence: a systematic
      literature review.
AB  - A literature review revealed the following: key work factors associated with
      psychological ill health and sickness absence in staff were long hours worked,
      work overload and pressure, and the effects of these on personal lives; lack of
      control over work; lack of participation in decision making; poor social support;
      and unclear management and work role. There was some evidence that sickness
      absence was associated with poor management style. Successful interventions that
      improved psychological health and levels of sickness absence used training and
      organisational approaches to increase participation in decision making and
      problem solving, increase support and feedback, and improve communication. It is
      concluded that many of the work related variables associated with high levels of
      psychological ill health are potentially amenable to change. This is shown in
      intervention studies that have successfully improved psychological health and
      reduced sickness absence.

PMID- 12499451
TI  - The effectiveness of current approaches to workplace stress management in the
      nursing profession: an evidence based literature review.
AB  - The effectiveness of current approaches to workplace stress management for nurses
      was assessed through a systematic review. Seven randomised controlled trials and
      three prospective cohort studies assessing the effectiveness of a stress
      management programmes were identified and reviewed. The quality of research
      identified was weak. There is more evidence for the effectiveness of programmes
      based on providing personal support than environmental management to reduce
      stressors. However, since the number and quality of studies is low, the question
      as to which, if any, approach is more effective cannot be answered definitively.
      Further research is required before clear recommendations for the use of
      particular interventions for nursing work related stress can be made.

PMID- 12499452
TI  - Dose-response patterns for vibration-induced white finger.
AB  - AIMS: To investigate alternative relations between cumulative exposures to hand
      transmitted vibration (taking account of vibration magnitude, lifetime exposure
      duration, and frequency of vibration) and the development of white finger
      (Raynaud's phenomenon). METHODS: Three previous studies have been combined to
      provide a group of 1557 users of powered vibratory tools in seven occupational
      subgroups: stone grinders, stone carvers, quarry drillers, dockyard caulkers,
      dockyard boilermakers, dockyard painters, and forest workers. The estimated total
      operating duration in hours was thus obtained for each subject, for each tool,
      and for all tools combined. From the vibration magnitudes and exposure durations,
      seven alternative measurements of cumulative exposure were calculated for each
      subject, using expressions of the form: dose = summation operator a(m)(i)t(i),
      where a(i) is the acceleration magnitude on tool i, t(i) is the lifetime exposure
      duration for tool i, and m = 0, 1, 2, or 4. RESULTS: For all seven alternative
      dose measures, an increase in dose was associated with a significant increase in
      the occurrence of vibration-induced white finger, after adjustment for age and
      smoking. However, dose measures with high powers of acceleration (m > 1) faired
      less well than measures in which the weighted or unweighted acceleration, and
      lifetime exposure duration, were given equal weight (m = 1). Dose determined
      solely by the lifetime exposure duration (without consideration of the vibration
      magnitude) gave better predictions than measures with m greater than unity. All
      measures of dose calculated from the unweighted acceleration gave better
      predictions than the equivalent dose measures using acceleration frequency
      weighted according to current standards. CONCLUSIONS: Since the total duration of
      exposure does not discriminate between exposures accumulated over the day and
      those accumulated over years, a linear relation between vibration magnitude and
      exposure duration seems appropriate for predicting the occurrence of vibration
      induced white finger. Poorer predictions were obtained when the currently
      recommended frequency weighting was employed than when accelerations at all
      frequencies were given equal weight. Findings suggest that improvements are
      possible to both the frequency weighting and the time dependency used to predict
      the development of vibration-induced white finger in current standards.

PMID- 12499453
TI  - Organisational justice and health of employees: prospective cohort study.
AB  - AIMS: To examine the association between components of organisational justice
      (that is, justice of decision making procedures and interpersonal treatment) and
      health of employees. METHODS: The Poisson regression analyses of recorded all
      cause sickness absences with medical certificate and the logistic regression
      analyses of minor psychiatric morbidity, as assessed by the General Health
      Questionnaire, and poor self rated health status were based on a cohort of 416
      male and 3357 female employees working during 1998-2000 in 10 hospitals in
      Finland. RESULTS: Low versus high justice of decision making procedures was
      associated with a 41% higher risk of sickness absence in men (rate ratio (RR)
      1.4, 95% confidence interval (CI) 1.1 to 1.8), and a 12% higher risk in women (RR
      1.1, 95% CI 1.0 to 1.2) after adjustment for baseline characteristics. The
      corresponding odds ratios (OR) for minor psychiatric morbidity were 1.6 (95% CI
      1.0 to 2.6) in men and 1.4 (95% CI 1.2 to 1.7) in women, and for self rated
      health 1.4 in both sexes. In interpersonal treatment, low justice increased the
      risk of sickness absence (RR 1.3 (95% CI 1.0 to 1.6) and RR 1.2 (95% CI 1.2 to
      1.3) in men and women respectively), and minor psychiatric morbidity (OR 1.2 in
      both sexes). These figures largely persisted after control for other risk factors
      (for example, job control, workload, social support, and hostility) and they were
      replicated in initially healthy subcohorts. No evidence was found to support the
      hypothesis that organisational justice would represent a consequence of health
      (reversed causality). CONCLUSIONS: This is the first longitudinal study to show
      that the extent to which people are treated with justice in workplaces
      independently predicts their health.

PMID- 12499455
TI  - Asbestos related diseases from environmental exposure to crocidolite in Da-yao,
      China. I. Review of exposure and epidemiological data.
AB  - BACKGROUND: Scattered patches of crocidolite, one form of asbestos, were found in
      the surface soil in the rural county of Da-yao in southwestern China. In 1983,
      researchers from the West China University of Medical Sciences (WCUMS) discovered
      that residents of two villages in Da-yao had hyperendemic pleural plaques and
      excessive numbers of pleural mesotheliomas. AIMS: To review and summarise
      epidemiological studies, along with other relevant data, and to discuss the
      potential contribution to environmental risk assessment. METHODS: This report is
      based on a review of several clinical/epidemiological studies conducted by WCUMS
      researchers since 1984, which included one cross sectional medical examination
      survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three
      retrospective cohort mortality studies. Additional information acquired from
      reviewing original data first hand during a personal visit along with an
      interview of medical specialists from Da-yao County Hospital was also
      incorporated. RESULTS: The prevalence of pleural plaque was 20% among peasants in
      Da-yao over 40 years of age in the cross sectional survey. The average number of
      mesothelioma cases was 6.6 per year in the 1984-95 period and 22 per year in the
      1996-99 period, in a population of 68 000. For those mesothelioma cases that were
      histology confirmed, there were 3.8 cases/year in the first period and 9
      cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis.
      Lung cancer deaths were significantly increased in all three cohort studies. The
      annual mortality rate for mesothelioma was 85 per million, 178 per million, and
      365 per million for the three cohort studies, respectively. The higher exposed
      peasants had a fivefold increased mesothelioma mortality compared to their lower
      exposed counterparts. There were no cases of mesothelioma in the comparison
      groups where no crocidolite was known to exist in the environment. In the third
      cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The
      ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3,
      3.0, and 1.2, respectively). CONCLUSIONS: The observation of numerous
      mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime
      exposure to crocidolite asbestos. The finding of cases dying at a younger age and
      the relatively high ratio of mesothelioma cases to lung cancer could also be
      another unique result of lifetime environmental exposure to crocidolite asbestos.
      Although the commercial use of crocidolite has been officially banned since 1984,
      the incidence of mesothelioma has continued to show a steady increase,
      particularly among peasants. Since the latency of mesothelioma is approximately
      30-40 years, the ban had little effect in the 1990s. The increased awareness and
      changes in diagnosis over time may also contribute to the increase. Furthermore,
      exposure to asbestos stoves and walls continued. The government implemented
      reduction of these exposures. However, from a public health standpoint, the most
      important issue is the complete avoidance of further exposure to asbestos.

PMID- 12499456
TI  - The impact of roster changes on absenteeism and incident frequency in an
      Australian coal mine.
AB  - BACKGROUND: The occupational health and safety implications associated with
      compressed and extended work periods have not been fully explored in the mining
      sector. AIMS: To examine the impact on employee health and safety of changes to
      the roster system in an Australian coal mine. METHODS: Absenteeism and incident
      frequency rate data were collected over a 33 month period that covered three
      different roster schedules. Period 1 covered the original 8-hour/7-day roster.
      Period 2 covered a 12-month period under a 12-hour/7-day schedule, and period 3
      covered a 12-month period during which a roster that scheduled shifts only on
      weekdays, with uncapped overtime on weekends and days off (12-hour/5-day) was in
      place. Data were collected and analysed from the maintenance, mining, and coal
      preparation plant (CPP) sectors. RESULTS: The only significant change in
      absenteeism rates was an increase in the maintenance sector in the third data
      collection period. Absenteeism rates in the mining and CPP sectors were not
      different between data collection periods. The increase in the maintenance sector
      may be owing to: (1) a greater requirement for maintenance employees to perform
      overtime as a result of the roster change compared to other employee groups; or
      (2) greater monotony associated with extended work periods for maintenance
      employees compared to others. After the first roster change, accident incident
      frequency decreased in the CPP sector but not in the other sectors. There was no
      effect on incident frequency after the second roster change in any sector.
      CONCLUSIONS: The current study did not find significant negative effects of a 12
      hour pattern, when compared to an 8-hour system. However, when unregulated and
      excessive overtime was introduced as part of the 12-hour/5-day roster,
      absenteeism rates were increased in the maintenance sector. The combination of
      excessive work hours and lack of consultation with employees regarding the second
      change may have contributed to the overall negative effects.

PMID- 12499458
TI  - Combined effect of smoking and occupational exposure to noise on hearing loss in
      steel factory workers.
AB  - BACKGROUND: Evidence has accumulated concerning the adverse effects of smoking on
      hearing acuity, but it is not clear whether smoking modifies the association
      between exposure to noise and hearing loss. AIMS: To examine the synergistic
      effect of these variables on hearing. METHODS: Data used were derived from
      periodic health examinations for 4624 steel company workers in Japan and included
      audiometry testing and information on smoking habits. Occupational exposure to
      noise was determined based on company records. Logistic regression was used to
      examine the dose-response association between smoking and hearing loss. The
      Cochran-Mantel-Haenszel method was used to calculate the prevalence rate ratio
      (PRR) of hearing loss for each combination of smoking and noise exposure factors,
      taking non-smokers not exposed to occupational noise as a reference. The
      interaction between smoking and noise exposure was assessed using a synergistic
      index, which equals 1 when the joint effect is additive. RESULTS: Smoking was
      associated with increased odds of having high frequency hearing loss in a dose
      response manner. The PRR for high frequency hearing loss among smokers exposed to
      occupational noise was 2.56 (95% CI 2.12 to 3.07), while the PRR for smokers not
      exposed to noise was 1.57 (95% CI 1.31 to 1.89) and the PRR for non-smokers
      exposed to noise was 1.77 (95% CI 1.36 to 2.30). The synergistic index was 1.16.
      Smoking was not associated with low frequency hearing loss. CONCLUSIONS: Smoking
      may be a risk factor for high frequency hearing loss, and its combined effect on
      hearing with exposure to occupational noise is additive.

PMID- 12499457
TI  - Update of predictions of mortality from pleural mesothelioma in the Netherlands.
AB  - AIMS: To predict the expected number of pleural mesothelioma deaths in the
      Netherlands from 2000 to 2028 and to study the effect of main uncertainties in
      the modelling technique. METHODS: Through an age-period-cohort modelling
      technique, age specific mortality rates and cohort relative risks by year of
      birth were calculated from the mortality of pleural mesothelioma in 1969-98.
      Numbers of death for both sexes were predicted for 2000 to 2028, taking into
      account the most likely demographic development. In a sensitivity analysis the
      relative deviation of the future death toll and peak death number were studied
      under different birth cohort risk assumptions. RESULTS: The age-cohort model on
      mortality 1969-98 among men showed the highest age specific death rates in the
      oldest age group (79 per 100 000 person-years in the age group 80-84 years) and
      the highest relative risks for the birth cohorts of 1938-42 and 1943-47. Among
      men a small period effect was observed. The age-cohort model was considered the
      best model for predicting future mortality. The most plausible scenario predicts
      an increase in pleural mesothelioma mortality up to 490 cases per year in men,
      with a total death toll close to 12 400 cases during 2000-28. However, using
      different assumptions this death toll could rise to nearly 15 000 in men (20%
      increase). Mortality among women remains low, with a total death toll of about
      800 cases. It is predicted that the total death toll in the period 2000-28 is 44%
      lower than previous predictions using mortality data from 1969 to 1993.
      CONCLUSION: Adding five recent years of observed mortality in an age-cohort model
      resulted in a 44% lower prediction of the future death toll of pleural
      mesothelioma. A statistically significant period effect was observed, possibly
      influenced by initial asbestos safety guidelines in the 1970s and introduction of
      the ICD-10 codification.

PMID- 12499459
TI  - Periportal fibrosis and other liver ultrasonography findings in vinyl chloride
      workers.
AB  - AIMS: To investigate the presence of liver lesions and their relation with vinyl
      chloride monomer (VCM) exposure or other personal risk factors, in workers
      involved in the production of VCM and polyvinyl chloride (PVC). METHODS: A liver
      ultrasonography examination was conducted in 757 workers, some of whom had long
      standing service in the production of VCM and PVC. The study involved: assessment
      of individual past and present VCM exposure of each worker; collection of past
      personal health history, lifestyle and personal data; routine liver function
      tests; and liver ultrasonography. RESULTS: No cases of liver malignancies were
      detected. Angiomas and liver cysts were found with a frequency of occurrence
      within the expected range of the general population. The main findings consisted
      of hepatomegaly (34.7%), steatosis (31.8%), and periportal fibrosis (16.0%). A
      logistic regression analysis indicated that hepatomegaly and steatosis were
      associated with obesity and lipid metabolism disturbances and not with VCM
      exposure. Periportal fibrosis, in addition to constitutional or dietary factors,
      was shown to be associated with VCM exposure, but only when maximum exposure in
      the subject's history had been at least 200 ppm as a yearly average; no effects
      were observed at 50 ppm or below. CONCLUSIONS: Workers exposed to 200 ppm VCM for
      at least one year have a fourfold increased risk of developing periportal liver
      fibrosis. Liver ultrasonography is a suitable and important diagnostic test for
      the medical surveillance of vinyl chloride workers.

PMID- 12499460
TI  - Multiple sclerosis in nurse anaesthetists.
AB  - BACKGROUND: Volatile anaesthetics are chemically related to organic solvents used
      in industry. Exposure to industrial solvents may increase the incidence of
      multiple sclerosis (MS). AIM: To examine the risk among nurse anaesthetists of
      contracting MS. METHODS: Nurses with MS were identified by an appeal in the
      monthly magazine of the Swedish Nurse Union and a magazine of the Neurological
      Patients Association in Sweden. Ninety nurses with MS responded and contacted our
      clinic. They were given a questionnaire, which was filled in by 85 subjects; 13
      of these were nurse anaesthetists. The questionnaire requested information about
      work tasks, exposure, diagnosis, symptoms, and year. The number of active nurse
      anaesthetists was estimated based on information from the National Board of
      Health and Welfare and The Nurse Union. Incidence data for women in the region of
      Gothenburg and Denmark were used as the reference to estimate the risk by
      calculation of the standardised incidence ratio (SIR). RESULTS: Eleven of the 13
      nurse anaesthetists were exposed to anaesthetic gases before onset of MS. Mean
      duration of exposure before diagnosis was 14.4 years (range 4-27 years). Ten
      cases were diagnosed in the study period 1980-99, resulting in significantly
      increased SIRs of 2.9 and 2.8 with the Gothenburg and the Danish reference data,
      respectively. CONCLUSION: Although based on crude data and a somewhat approximate
      analysis, this study provides preliminary evidence for an excess risk of MS in
      nurse anaesthetists. The risk may be even greater than observed, as the case
      ascertainment might have been incomplete because of the crude method applied.
      Further studies in this respect are clearly required to more definitely assess
      the risk.

PMID- 12499461
TI  - Visual and ocular changes associated with exposure to two tertiary amines.
AB  - AIMS: To determine if exposure to dimethylisopropanolamine (DMIPA) and
      dimethylaminoethanol (DMAE) in a label printing plant was associated with visual
      disturbances and/or ocular changes. METHODS: Questionnaires, eye examinations
      (visual acuity, contrast sensitivity at 2.5% and 1.25% contrast, slit lamp
      biomicroscopy, and pachymetry), and industrial hygiene monitoring for DMIPA and
      DMAE were performed over a two week period. RESULTS: Eighty nine per cent of line
      workers reported having experienced blurry vision while at work in the past 12
      months, compared to 12.5% of prime workers. A total of 108 full shift personal
      breathing zone (PBZ) air samples for the amines were collected. The mean time
      weighted average (TWA) concentration of DMIPA was significantly higher in the
      line division than in the prime division, as was the mean TWA concentration for
      total amines. The mean TWA concentration of DMAE was higher in the prime division
      than the line division. Higher levels of total amines were associated with
      increased risk of reporting blurry vision, halo vision, and blue-grey vision. The
      risk of corneal opacity rose with increasing exposure to total amines. The
      prevalence of corneal opacity also increased with increasing concentration of
      total amines. Median corneal thickness increased with increasing grades of
      corneal opacity. There was a statistically significant relation between total
      amine concentration and increased risk of reduced bilateral visual acuity and
      2.5% contrast sensitivity. CONCLUSIONS: Exposure to tertiary amines was
      associated with blurry, halo, and blue-grey vision, corneal opacity, and
      decrements in visual acuity and contrast sensitivity at 2.5% contrast.

PMID- 12499462
TI  - Occupational asthma from fungicides fluazinam and chlorothalonil.
AB  - We report two cases of occupational asthma caused by sensitisation to powdered
      fungicides fluazinam and chlorothalonil, from the same fungicide formulation
      plant. Both developed work related lower respiratory symptoms after a latent
      interval of asymptomatic exposure. The diagnosis in each case was confirmed with
      a serial peak flow record in the workplace followed by specific inhalation tests.
      These fungicides are known to cause dermatitis; this report indicates that these
      compounds can induce specific immunological reactions in the airways as well as
      skin.

PMID- 12499464
TI  - Diagnosis of CIDP.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease
      that targets the myelin sheaths of peripheral nerves. In clinical practice the
      diagnosis is often difficult to make because of the clinical heterogeneity of the
      disease, its multifocality and predilection for proximal nerve segments, and the
      limitations of our electrophysiologic and pathologic techniques. Although there
      are rather stringent research criteria for selecting patients to clinical trials,
      there are no generally agreed-on clinical diagnostic criteria for CIDP, and
      application of the research criteria to routine clinical practice would miss the
      diagnosis in a majority of patients. Because of this uncertainty, the prevalence
      of CIDP is greatly underestimated, and patients are often left untreated despite
      progression of their disease. However, given what is known about the clinical
      presentation and pathophysiology of CIDP, patients with neuropathy of otherwise
      unknown etiology are more likely to have CIDP than idiopathic axonal neuropathy,
      and warrant a trial of therapy if they have nerve conduction velocities below the
      lower limits of normal, prolongation of F-waves beyond the normal range, or
      presence of conduction block or temporal dispersion. A favorable response to
      therapy, consisting of stabilization or improvement of the neuropathy, would
      confirm the diagnosis.

PMID- 12499465
TI  - Immune mechanisms in chronic inflammatory demyelinating neuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune
      mediated peripheral neuropathy. In recent years, the application of basic
      principles of general immunology has widened our understanding of the etiology
      and immunopathogenesis of this neuropathy. Although both cellular and humoral
      factors have been implicated, the data are still fragmentary and insufficient for
      a unified hypothesis. This review summarizes the present knowledge of the
      fundamental immune mechanisms related to the immunopathogenesis of CIDP and
      discusses the role of T cells, activated macrophages, cytokines, co-stimulatory
      molecules, and anti-myelin antibodies. An important factor in current approaches
      to the therapy of CIDP is the increasingly recognized concomitant axonal loss
      that occurs secondary to primary demyelination.

PMID- 12499466
TI  - Mechanisms of action of IVIg and therapeutic considerations in the treatment of
      acute and chronic demyelinating neuropathies.
AB  - Intravenous immunoglobulin (IVIg) is an immunomodulating agent that has multiple
      activities, including modulation of complement activation products, suppressing
      idiotypic antibody, saturating Fc receptors on macrophages, and suppressing
      various inflammatory mediators including cytokines, chemokines, and
      metalloproteinases. Because all these factors are implicated to various degrees
      in the pathogenesis of immune-mediated demyelination of the PNS, administration
      of IVIg could be beneficial in treating neuropathies by suppressing the immune
      mediated processes that are directed against myelin or axonal antigenic targets.
      This article outlines the actions of IVIg in CIDP and other autoimmune
      neuropathies based on data derived from in vivo and in vitro studies. The
      predominant mechanisms by which IVIg exerts its action on these neuropathies
      appear to be a combined effect on complement inactivation, neutralization of
      idiotypic antibodies, cytokine inhibition, and saturation of Fc receptors on
      endoneurial macrophages.

PMID- 12499467
TI  - Therapy of CIDP and related immune-mediated neuropathies.
AB  - This study assesses the data supporting the current use of immunotherapy for
      management of neuropathies with a presumed autoimmune basis. Immune or
      inflammatory mechanisms are implicated in an increasing number of disorders that
      involve damage to peripheral nerves and sensory ganglia. The most prevalent of
      these is chronic inflammatory demyelinating polyradiculoneuritis (CIDP). CIDP is
      clinically distinguishable from a series of other immune- or inflammation
      mediated neuropathies. These include the following: multifocal acquired
      demyelinating sensory and motor (MADSAM) neuropathy associated with conduction
      block; brachial or lumbar plexitis; multifocal motor neuropathy, a distal
      demyelinating neuropathy associated with antibodies to the myelin-associated
      glycoprotein (MAG); and sensory neuronopathy. We reviewed the literature of the
      National Library of Medicine using the above terms and their variations. The
      results from short-term, randomized, controlled trials support the efficacy of
      intravenous immunoglobulin (IVIg), plasma exchange, and corticosteroids in the
      treatment of CIDP, and the efficacy of IVIg in the treatment of MMN. Only
      anecdotal experience is available for assessing the treatment of MADSAM
      neuropathy, lumbar and brachial plexitis, MAG neuropathy, and sensory
      neuronopathy. Cytotoxic and immunosuppressive drugs are frequently used to treat
      patients with many of these disorders when they are refractory to standard
      treatments, but no controlled trials have been done to support their use. This
      review discusses the complications and criteria for use of these therapies.
      Selecting the best immunotherapy for an individual patient should be based on the
      proven efficacy of a given regimen in modulating the pathophysiology underlying
      the neuropathy, the anticipated duration of disease, and the patient's age,
      reproductive status, and coexisting metabolic derangement.

PMID- 12499468
TI  - Composition and properties of IVIg preparations that affect tolerability and
      therapeutic efficacy.
AB  - The use of intravenous immune globulin (IVIg) has increased significantly in the
      past decade, benefiting a wide variety of immune diseases. Seven different
      formulations of IVIg are now licensed in the United States. Although all contain
      pooled IgG, there are differences in their production and composition that affect
      their efficacy, tolerability, and side-effect profile. Important variables
      include concentration, volume, osmolality, sodium, and sugar content. This
      article reviews what is known about the composition and properties of the various
      IVIg formulations that might affect the therapeutic outcome.

PMID- 12499469
TI  - Intravenous gammaglobulin (IVIg) for treatment of CIDP and related immune
      mediated neuropathies.
AB  - Intravenous immune globulin (IVIg) is considered an effective and safe treatment
      for autoimmune neuropathies, especially in comparison to the alternative
      treatments such as corticosteroids, chemotherapy, and plasmapheresis. Patients
      are frequently given a standard induction dose of 2 g/kg, which may be followed
      by maintenance therapy as needed. Mild infusion-related reactions are frequent
      but these can often be controlled by slowing the infusion rate or by symptomatic
      medications. Serious adverse effects are rare and can include thromboembolic
      events, renal failure, anaphylaxis, or septic meningitis. Patients with IgA
      deficiency are at risk for anaphylaxis. Immobility, increased serum viscosity,
      and preexisting vascular disease can increase the risk for thromboembolic events.
      Preexisting renal insufficiency or the use of sucrose-containing IVIg
      preparations can increase the risk for renal failure, and patients with migraine
      are at risk for development of aseptic meningitis. Screening patients for risk
      factors that predispose to development of adverse events may reduce the incidence
      of complications.

PMID- 12499470
TI  - Regulatory and reimbursement issues in treating patients with immune-mediated
      neuropathies.
AB  - Neurologists are prescribing intravenous immunoglobulin (IVIg) with increasing
      frequency to treat many neurologic conditions that have a proven or presumed
      autoimmune or inflammatory pathogenesis. Although IVIg is not FDA approved for
      any neurologic condition, physicians can safely prescribe it for several
      disorders with reasonable certainty that the cost for the agent will be
      reimbursed by third-party carriers. This article discusses present FDA
      indications for using IVIg, off-label uses of IVIg, policies of third-party
      payers toward reimbursement, the Local Medical Review Policy of Medicare, coding,
      billing, and reimbursement for IVIg infusion, and approaches to use when
      reimbursement is delayed or denied.

PMID- 12499471
TI  - Holoprosencephaly: the face predicts the brain; the image predicts its function.

PMID- 12499472
TI  - GDAP1 mutations in CMT4: axonal and demyelinating phenotypes?: The exception
      "proves the rule".

PMID- 12499473
TI  - Immunization and MS: a summary of published evidence and recommendations.
AB  - OBJECTIVE: To review the risk of MS exacerbations after infectious episodes
      potentially preventable by vaccination, and the risks and benefits of immunizing
      patients with MS. METHODS: The authors searched MEDLINE (1966 to January 2001;
      U.S. National Library of Medicine, Bethesda, MD), HealthSTAR, and Cumulative
      Index to Nursing and Allied Health Literature (CINAHL) database (Cinahl
      Information Systems, Glendale, CA) for English-language articles. Each study was
      summarized and rated for quality of evidence. Then feasible data were pooled and
      analyzed in meta-analysis. RESULTS: The risk of contracting common infectious
      diseases in patients with MS is not well established. There is strong evidence
      for an increased risk of MS exacerbations during weeks around an infectious
      episode. There is strong evidence against an increased risk of MS exacerbation
      after influenza immunization. There is no evidence that hepatitis B, varicella,
      tetanus, or Bacille Calmette-Guerin vaccines increase the risk of MS
      exacerbations. Insufficient evidence was found for other vaccines. CONCLUSIONS:
      Evidence supports 1) strategies to minimize the risk of acquiring infectious
      diseases that may trigger exacerbations of MS; and 2) the safety of using
      influenza, hepatitis B, varicella, tetanus, and Bacille Calmette-Guerin (BCG)
      vaccines in patients with MS.

PMID- 12499474
TI  - Middle interhemispheric variant of holoprosencephaly: a distinct
      cliniconeuroradiologic subtype.
AB  - BACKGROUND: The middle interhemispheric variant (MIH) is a subtype of
      holoprosencephaly (HPE) in which the posterior frontal and parietal areas lack
      midline separation, whereas more polar areas of the cerebrum are fully cleaved.
      While the neuroradiologic features of this subtype have been recently detailed,
      the clinical features are largely unknown. OBJECTIVE: To present the clinical
      manifestations of MIH and to compare them with classic subtypes (alobar,
      semilobar, and lobar) of HPE. METHODS: The authors evaluated 15 patients with MIH
      in a multicenter study. Neuroimaging and clinical data were collected and
      correlated. They compared the data with those of 68 patients who had classic HPE.
      RESULTS: The frequency of endocrinopathy in MIH (0%) was lower compared with the
      classic subtypes (72%) (p < 0.0001). This correlated with the lack of
      hypothalamic abnormalities. The percentage of patients with seizures (40%) did
      not significantly differ from classic HPE. Spasticity was the most common motor
      abnormality, seen in 86% of MIH patients, similar to other subtypes. The
      frequency of choreoathetosis in MIH (0%) was lower than that for semilobar HPE
      (41%) (p < 0.0039). This correlated with the lack of caudate and lentiform nuclei
      abnormalities. Developmental functions, including mobility, upper-extremity
      function, and language, of the MIH group were similar to the least severe classic
      type, lobar HPE. CONCLUSION: MIH is a recognizable variant of HPE with differing
      clinical prognosis. Similar to the lobar subtype by functional measures, MIH
      differs from classic HPE by the absence of endocrine dysfunction and
      choreoathetosis.

PMID- 12499475
TI  - Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy.
AB  - BACKGROUND: Mutations in the ganglioside-induced differentiation-associated
      protein 1 gene (GDAP1) were recently shown to be responsible for autosomal
      recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as
      well as AR axonal CMT with vocal cord paralysis. METHODS: The coding region of
      GDAP1 was screened for the presence of mutations in seven families with AR CMT in
      which the patients were homozygous for markers of the CMT4A locus at chromosome
      8q21.1. RESULTS: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a
      1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon
      6 (c.844C>T, R282C). CONCLUSIONS: Mutations in GDAP1 are a frequent cause of AR
      CMT. They result in an early-onset, severe clinical phenotype. The range of nerve
      conduction velocities (NCV) is variable. Some patients have normal or near normal
      NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV
      compatible with demyelination. The peripheral nerve biopsy findings are equally
      variable and show features of demyelination and axonal degeneration.

PMID- 12499476
TI  - Thalidomide-induced neuropathy.
AB  - BACKGROUND: Thalidomide is effective for the treatment of some refractory
      dermatologic and oncologic diseases. Toxic neuropathy limits its use, as
      embryopathy can be avoided by contraceptive measures. OBJECTIVE: To describe the
      clinical, electrophysiologic, and pathologic features of thalidomide-induced
      peripheral neuropathy. METHODS: Clinical and electrophysiologic examinations were
      performed in seven patients with thalidomide-induced peripheral neuropathy.
      Thalidomide was used for graft-vs-host disease, pyoderma gangrenosum, and discoid
      lupus with dosages ranging from 100 to 1,200 mg/day for 5 to 16 months
      (cumulative dosages of 24 to 384 g). RESULTS: All seven patients had clinical and
      electrophysiologic evidence of a sensory more than motor, axonal, length
      dependent polyneuropathy that presented as painful paresthesias or numbness.
      Sural nerve biopsies, done in three patients, showed evidence of Wallerian
      degeneration and loss of myelinated fibers. The symptoms, signs, and
      electrophysiologic data correlated with total cumulative dose of thalidomide.
      CONCLUSIONS: Thalidomide induces a dose-dependent sensorimotor length-dependent
      axonal neuropathy; it should be judiciously used with close neurologic
      monitoring.

PMID- 12499477
TI  - Modafinil reduces excessive somnolence and enhances mood in patients with
      myotonic dystrophy.
AB  - OBJECTIVE: To evaluate the potential of modafinil in reducing excessive daytime
      somnolence (EDS) and enhancing indexes of quality of life and mood in patients
      with myotonic dystrophy (DM). METHODS: Forty patients with DM were randomized to
      receive modafinil and placebo for 14 days each, using a double-blind, cross-over
      design. Before and after each trial, subjects completed handgrip strength
      testing, spirometry, and quality-of-life measures (RAND). On days 7 and 14, each
      subject completed the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness
      Scale (SSS), and the Profile of Mood States (POMS). RESULTS: ESS scores were
      lower while taking modafinil (mean 248 mm; 95% confidence limit 220 to 276 mm) as
      compared with placebo (309 mm; 281 to 336 mm) (p < 0.001). Mean SSS scores were
      also lower during the modafinil trial (3.05; 2.77 to 3.33) than during the
      placebo trial (3.45; 3.18 to 3.71) (p < 0.05). The POMS indicated that modafinil
      decreased fatigue-inertia (p < 0.001) and increased vigor-activity and tension
      anxiety (p < 0.001) indexes. The total mood disturbance score was also decreased
      during the modafinil trial as compared with placebo (p < 0.05). The RAND quality
      of-life measures of energy (p < 0.001) and health change (p < 0.05) were both
      significantly enhanced during the modafinil treatment phase. No changes in
      maximal grip strength or forced expired volume in 1 second were detected over the
      course of the study. Headache was the most frequently reported adverse event.
      Four patients withdrew from the study, three because of side effects (two during
      modafinil ingestion and one during placebo ingestion). CONCLUSION: Modafinil
      reduces somnolence and improves mood in patients with DM.

PMID- 12499478
TI  - Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta
      subunit mutation.
AB  - OBJECTIVE: To determine the molecular basis of a disabling congenital myasthenic
      syndrome (CMS) observed in two related and one unrelated Arab kinship.
      BACKGROUND: CMS can arise from defects in presynaptic, synaptic basal lamina
      associated, or postsynaptic proteins. Most CMS are postsynaptic, and most reside
      in the AChR epsilon subunit; only two mutations have been reported in the AChR
      delta subunit to date. METHODS: Cytochemistry, electron microscopy, alpha
      bungarotoxin binding studies, microelectrode and patch-clamp recordings, mutation
      analysis, mutagenesis, and expression studies in human embryonic kidney cells
      were employed. RESULTS: Endplate studies showed AChR deficiency, fast decaying,
      low-amplitude endplate currents, and abnormally brief channel opening events.
      Mutation analysis revealed a novel homozygous missense mutation (deltaP250Q) of
      the penultimate proline in the first transmembrane domain (TMD1) of the AChR
      delta subunit. Expression studies indicate that deltaP250Q (1) hinders
      delta/alpha subunit association during early AChR assembly; (2) hinders opening
      of the doubly occupied closed receptor (A(2)R); and (3) speeds the dissociation
      of acetylcholine from A(2)R. Mutagenesis studies indicate that deltaP250L also
      has fast-channel effects, whereas epsilon P245L and epsilon P245Q, identical
      mutations of the corresponding proline in the epsilon subunit, have mild slow
      channel effects. CONCLUSIONS: deltaP250Q represents the third mutation observed
      in the AChR delta subunit. The severe phenotype caused by deltaP250Q is
      attributed to endplate AChR deficiency, fast decay of the synaptic response, and
      lack of compensatory factors. That the penultimate prolines in TMD1 of the delta
      and epsilon subunits exert a reciprocal regulatory effect on the length of the
      channel opening bursts reveals an unexpected functional asymmetry between the two
      subunits.

PMID- 12499479
TI  - Periodic leg movements in REM sleep behavior disorder and related autonomic and
      EEG activation.
AB  - OBJECTIVE: To assess the frequency of periodic leg movements (PLM) in idiopathic
      REM sleep behavior disorder (RBD) and to analyze their polysomnographic
      characteristics and associated autonomic and cortical activation. BACKGROUND: PLM
      during sleep (PLMS) and wakefulness (PLMW) are typical features of restless legs
      syndrome (RLS), but are also frequently observed in patients with RBD. METHODS:
      Forty patients with idiopathic RBD underwent one night of polysomnographic
      recording to assess PLMS frequency. PLM features, PLMS-related cardiac activation
      during stage 2 sleep, and EEG changes were analyzed in 15 of these patients with
      RBD. Results were compared with similar data obtained in 15 sex- and age-matched
      patients with primary RLS. RESULTS: Twenty-eight (70%) of 40 patients with RBD
      showed a PLMS index greater than 10. No between-group differences were found in
      sleep architecture or indexes of PLMW and PLMS during non-REM sleep, but a trend
      for a higher PLMS index during REM sleep was found in patients with RBD. PLM mean
      duration and interval in the two conditions were similar. A transient tachycardia
      followed by a bradycardia was observed in close association with every PLMS in
      both groups, but the amplitude of the cardiac activation was significantly
      reduced in patients with RBD. In addition, significantly fewer PLMS were
      associated with microarousal in this condition. CONCLUSIONS: Periodic leg
      movements are very common in idiopathic RBD, occurring in all stages of sleep,
      especially during REM sleep. In idiopathic RBD, the reduction of cardiac and EEG
      activation associated with PLMS suggests the presence of an impaired autonomic
      and cortical reactivity to internal stimuli.

PMID- 12499480
TI  - Severe neurologic complications after hematopoietic stem cell transplantation in
      children.
AB  - OBJECTIVE: To describe and evaluate the incidence and risk factors of severe
      neurologic events (SNE) in pediatric recipients of allogeneic or autologous
      hematopoietic stem cell transplantation (HSCT) for hematologic or nonhematologic
      diseases. METHODS: Retrospective analysis of 272 consecutive children admitted to
      the G. Gaslini Children's Research Institute and given HSCT (70 from unrelated
      donors, 115 from related donors, and 87 autologous) between June 1985 and January
      2001. RESULTS: Thirty-seven children (13.6%) developed SNE after a median of 90
      days (range, 5 days to 8.8 years) after HSCT. Cyclosporine A (CSA) neurotoxicity
      was the most frequent SNE (n = 21), followed by irradiation or chemotherapy
      injury (n = 7), CNS infections (n = 7), cerebrovascular events (n = 3), and
      immune-mediated etiology SNE (n = 2). Eleven patients (30%) died because of the
      neurologic complications. Type of HSCT, treatment with total body irradiation
      (TBI), acute graft-vs-host disease (GvHD), GvHD >grade 2, and treatment with CSA
      were associated with a significant increased risk of SNE. CONCLUSIONS: Severe
      neurologic complications are frequent (14%) among children receiving HSCT,
      causing 8.5% of deaths after transplant. Transplant from allogeneic donor,
      especially if unrelated, the development of severe acute GvHD grade >2, and the
      use of TBI in the preparative regimen are the main risk factors for such
      complications.

PMID- 12499481
TI  - A novel form of autosomal recessive pure hereditary spastic paraplegia maps to
      chromosome 13q14.
AB  - BACKGROUND: Hereditary spastic paraplegia (HSP) is a clinically and genetically
      heterogeneous disorder characterized by a progressive weakening and spasticity of
      the lower limbs. HSP is classified according to the presence or absence of
      accompanying neurologic problems and by the mode of inheritance. Currently, 17
      loci have been linked to the various forms of HSP. OBJECTIVE: To determine the
      chromosomal location of a gene causing pure autosomal recessive spastic
      paraplegia. METHODS: Genotyping using fluorescently labeled microsatellite
      markers was performed on three affected individuals and three unaffected
      individuals from a family displaying pure autosomal recessive HSP (ARHSP) and
      sensorineural deafness. All family members were then included in the analysis to
      narrow the genetic interval. Candidate genes were screened for the presence of
      mutations by heteroduplex analysis. RESULTS: The paraplegic trait linked to a 1.8
      Mb region of chromosome 13q14 flanked by the FLJ11712 gene and the microsatellite
      marker D13S270. The deafness did not link to this region and did not cosegregate
      with the paraplegic trait. CONCLUSION: The HSP that this family had represents a
      novel genetic form of pure ARHSP as no other form of HSP (autosomal dominant or
      recessive) has been linked to chromosome 13.

PMID- 12499482
TI  - Cognitive activity and incident AD in a population-based sample of older persons.
AB  - BACKGROUND: Participation in cognitively stimulating activities is hypothesized
      to be associated with risk of AD, but knowledge about this association is
      limited. METHODS: A biracial community in Chicago was censused, persons aged 65
      years and older were asked to participate in an interview, and 6,158 of 7,826
      (79%) eligible persons did so. As part of the interview, persons rated current
      frequency of participation in seven cognitive activities (e.g., reading a
      newspaper) and nine physical activities (e.g., walking for exercise) from which
      composite measures of cognitive and physical activity frequency were derived.
      Four years later, 1,249 of those judged free of AD were sampled for a detailed
      clinical evaluation of incident disease and 842 (74% of those eligible)
      participated. RESULTS: The composite measure of cognitive activity ranged from
      1.28 to 4.71 (mean 3.30; SD 0.59), with higher scores indicating more frequent
      activity. A total of 139 persons met National Institute of Neurological and
      Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association criteria for AD on clinical evaluation. In a logistic regression
      model adjusted for age, education, sex, race, and possession of the APOE epsilon4
      allele, a one-point increase in cognitive activity score was associated with a
      64% reduction in risk of incident AD (OR 0.36; 95% CI 0.20 to 0.65). By contrast,
      weekly hours of physical activity (mean 3.5; SD 5.1) was not related to disease
      risk (OR 1.04; 95% CI 0.98 to 1.10). Education was associated with risk of AD and
      a similar trend was present for occupation, but these effects were substantially
      reduced when cognitive activity was added to the model. CONCLUSION: Frequency of
      participation in cognitively stimulating activities appears to be associated with
      risk of AD and may partially explain the association of educational and
      occupational attainment with disease risk.

PMID- 12499483
TI  - Diet and risk of dementia: Does fat matter?: The Rotterdam Study.
AB  - OBJECTIVE: To examine whether high intake of total fat, saturated fatty acids
      (saturated fat), trans fatty acids (trans fat), and cholesterol and low intake of
      monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-6 PUFA,
      and n-3 PUFA are associated with increased risk of dementia and its subtypes.
      METHOD: Data from the Rotterdam Study, a prospective cohort study among elderly,
      were used. At baseline (1990 to 1993), 5,395 subjects had normal cognition, were
      noninstitutionalized, and underwent complete dietary assessment by a
      semiquantitative food-frequency questionnaire. The cohort was continuously
      monitored for incident dementia, and re-examinations were performed in 1993 to
      1994 and 1997 to 1999. The association between fat intake and incident dementia
      was examined by Cox's proportional hazards models. RESULTS: After a mean follow
      up of 6.0 years, 197 subjects developed dementia (146 AD, 29 vascular dementia).
      High intake of total, saturated, trans fat, and cholesterol and low intake of
      MUFA, PUFA, n-6 PUFA, and n-3 PUFA were not associated with increased risk of
      dementia or its subtypes. Rate ratios of dementia per standard deviation increase
      in intake were for total fat 0.93 (95% CI 0.81 to 1.07), for saturated fat 0.91
      (95% CI 0.79 to 1.05), for trans fat 0.90 (95% CI 0.77 to 1.06), for cholesterol
      0.93 (95% CI 0.80 to 1.08), for MUFA 0.96 (95% CI 0.84 to 1.10), for PUFA 1.05
      (95% CI 0.80 to 1.38), for n-6 PUFA 1.03 (95% CI 0.77 to 1.36), and for n-3 PUFA
      1.07 (95% CI 0.94 to 1.22). CONCLUSION: High intake of total, saturated, and
      trans fat and cholesterol and low intake of MUFA, PUFA, n-6 PUFA, and n-3 PUFA
      were not associated with increased risk of dementia or its subtypes.

PMID- 12499484
TI  - Course and prognosis in early-onset MS: comparison with adult-onset forms.
AB  - OBJECTIVES: To establish the prognostic role of clinical and demographic factors
      in a hospital-based cohort of MS patients categorized by age at clinical onset
      and clinical course. METHODS: Eighty-three patients with MS had a clinical onset
      of the disease in childhood (age <16 years; early-onset MS [EOMS]) and 710 in
      adult age (between 16 and 65 years; adult-onset MS [AOMS]). Patients were
      followed for a mean period of observation of 5 years. Univariate and multivariate
      analyses of clinical and demographic predictors for rapid progression and
      disability were performed using a stepwise Cox regression model with time
      dependent covariates. RESULTS: In EOMS, the Expanded Disability Status Scale
      (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a
      longer disease duration. The probability to reach growth disability and
      progression was significantly lower in EOMS than in AOMS. Median times to reach
      EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but
      the age at both endpoints was significantly lower in EOMS. In EOMS and AOMS, an
      irreversible disability was related to a secondary progressive course, a
      sphincteric system involvement at onset, and an older age at onset (in EOMS only
      for the group >14 years); in AOMS, other unfavorable factors were a pyramidal
      involvement at onset and a high relapse frequency in the first 2 years. The risk
      of entering secondary progression was significantly influenced by a high number
      of relapses in EOMS and by a higher age at onset and a short interattack interval
      in AOMS. CONCLUSION: A slower rate of progression of disease characterized EOMS
      patients, suggesting more plasticity to recover in developing CNS, but the early
      clinical manifestation cannot be considered a positive prognostic factor.

PMID- 12499485
TI  - Face encoding and psychometric testing in healthy dextrals with right hemisphere
      language.
AB  - OBJECTIVE: To document how right hemisphere language dominance in neurologically
      normal right-handed individuals affects lateralization of face encoding and level
      of performance in neuropsychological tests. METHODS: Three healthy right-handed
      adults with predominantly right hemisphere language activation during single-word
      or sentence-level processing were identified from 210 consecutive right-handed
      subjects studied using blood oxygenation level-dependent contrast fMRI. These
      three study subjects (S1 to S3) underwent a second scanning session where they
      performed word and face encoding. Their functional scans were contrasted with
      those obtained from six healthy control subjects (C1 to C6) with left hemisphere
      language dominance. Psychometric tests were performed on the study subjects.
      RESULTS: Right hemisphere-dominant language activation was reproduced in the
      second scanning session in the three study subjects. The extent to which the
      lateralization of face encoding was reversed varied. Right hemisphere language
      was associated with lower (but within normal) verbal IQ compared with performance
      IQ in two of three volunteers. Verbal and nonverbal memory scores were normal and
      did not differ appreciably. CONCLUSION: Right hemisphere-dominant language in
      healthy dextrals exists but is rare. The extent to which face encoding is
      reversed in these individuals is variable. Cognitive function does not appear to
      be significantly compromised even though some psychometric test scores are
      asymmetric in favor of nonverbal performance when the reversal of lateralization
      of face and word memory is not complete.

PMID- 12499486
TI  - Do quiescent arachnoid cysts alter CNS functional organization?: A fMRI and
      morphometric study.
AB  - OBJECTIVE: To investigate whether congenital and clinically quiescent arachnoid
      cysts (AC) in the left temporal fossa alter the functional organization of
      adjacent cortices. METHODS: fMRI mapping was applied in five right-handed
      asymptomatic patients to determine the functional organization of language.
      Moreover, morphometry was performed in each patient to gain the size of cortical
      surface areas and cortical thickness values in the neighboring brain adjacent to
      the AC and explicitly in the left opercular region. RESULTS: Four patients showed
      a clear left hemisphere language dominance regardless of the cyst size; a mixed
      laterality of language organization was found in the remaining patient. An
      interesting dissociation of morphometric data was assessed when comparing
      strongly language-related cortices in the inferior frontal gyrus with the entire
      neighboring cortices. Morphometry in the neighboring brain regions of the AC
      showed 1) overall reduced cortical surface areas and 2) a decrease in cortical
      thickness compared to the homologous right side. However, the surface area of the
      fronto-opercular region in the left inferior frontal gyrus-i.e., the pars
      triangularis and the pars opercularis-was larger on the left as compared to the
      right side. Both structures have earlier been identified to represent the
      morphologic substrate of language dominance in the left hemisphere. CONCLUSION:
      Arachnoid cysts do not disturb the normal asymmetry of hemisphere language
      organization despite delicate locations adjacent to the left inferior frontal
      gyrus.

PMID- 12499487
TI  - Elevation of blood beta-carboline alkaloids in essential tremor.
AB  - BACKGROUND: beta-Carboline alkaloids are normal body constituents but are also
      potent tremor-producing chemicals that are naturally present in the food chain.
      OBJECTIVE: To explore the hypothesis that high concentrations of beta-carboline
      alkaloids are associated with essential tremor (ET). METHODS: One hundred cases
      and 100 controls were frequency matched on age, sex, and ethnicity. Blood
      concentrations of harmane and harmine were quantified by high-performance liquid
      chromatography, blinded to clinical information. RESULTS: The mean log blood
      concentration of harmane was higher in cases than controls (0.72 +/- 0.53 vs 0.51
      +/- 0.64 g(-10)/mL; p = 0.01). A nonparametric test on nontransformed data
      (median harmane = 5.21 g(-10)/mL in cases and 2.28 g(-10)/mL in controls)
      confirmed this difference (p = 0.005). The mean log blood concentration of
      harmine was 0.20 +/- 0.48 g(-10)/mL in cases and 0.10 +/- 0.65 g (-10)/mL in
      controls (p = 0.20). Log harmane concentrations were stratified based on the
      median value; 62% of cases vs 39% of controls had a high log harmane
      concentration (p = 0.001). Mean log harmane concentration was similar in the
      cases with (0.74 +/- 0.58 g(-10)/mL) and without (0.71 +/- 0.50 g(-10)/mL) an
      affected relative (p = 0.83). CONCLUSIONS: Blood concentrations of harmane were
      measured in ET cases compared with controls. Concentrations were elevated in
      cases with and without a family history of ET.

PMID- 12499489
TI  - Strokes restricted to the insular cortex.
AB  - OBJECTIVE: To characterize clinically acute insular strokes from four patients
      with a first ever acute stroke restricted to the insula on MRI. METHODS: The
      authors studied the clinical presentation of four patients with a first ever
      acute stroke restricted to the insula on MRI. RESULTS: The authors found five
      main groups of clinical presentations: 1) somatosensory deficits in three
      patients with posterior insular stroke (two with a transient pseudothalamic
      sensory syndrome, one with partial distribution); 2) gustatory disorder in a
      patient with left posterior insular infarct; 3) vestibular-like syndrome, with
      dizziness, gait instability, and tendency to fall, but no nystagmus, in three
      patients with posterior insular strokes; 4) cardiovascular disturbances,
      consisting of hypertensive episodes in a patient with a right posterior insular
      infarct; and 5) neuropsychological disorders, including aphasia (left posterior
      insula), dysarthria, and transient somatoparaphrenia (right posterior insula).
      CONCLUSION: Strokes restricted to the posterior insula may present with
      pseudothalamic sensory and vestibular-like syndromes as prominent clinical
      manifestations, but also dysarthria and aphasia (in left lesions),
      somatoparaphrenia (right lesions) and gustatory dysfunction and blood pressure
      with hypertensive episodes in right lesions; we did not find acute dysphagia
      reported in anterior, insular strokes.

PMID- 12499490
TI  - Localizing value of torsional nystagmus in small midbrain lesions.
AB  - BACKGROUND: The topodiagnostic value and specificity of nystagmus in patients
      with mesencephalic lesions and its relation to tonic torsional deficits and
      vertical saccade deficits is controversial and anecdotal. METHODS: The authors
      examined 11 patients with vascular MRI-identified mesencephalic lesions and
      clinical evidence of vertical-torsional nystagmus on gaze straight ahead,
      focusing on the three-dimensional nystagmus components recorded with the three
      dimensional search coil technique. RESULTS: Combined lesions of the rostral
      interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the
      interstitial nucleus of Cajal (iC) are much more frequent than riMLF and, in
      particular, iC lesions alone. Eight patients showed contralesional torsional
      nystagmus with a conjugate vertical component on gaze straight ahead and had
      anatomic (MRI) and clinical evidence (slowing of vertical saccades) for riMLF
      involvement. Tonic ocular torsion and the subjective visual vertical were shifted
      to the contralesional side (n = 7). Torsional nystagmus to the ipsilesional side
      was uncommon (n = 3) and found in patients with midbrain lesions involving the
      iC, all of whom also had decreased time constants of the slow phases of gaze
      evoked nystagmus. CONCLUSIONS: Contrary to previous proposals, contralesional
      torsional nystagmus was the most frequent direction and is probably not
      compensatory for contralesional tonic ocular torsion. Small amplitude vertical
      saccades with normal velocities in association with ipsilesional torsional
      nystagmus may indicate isolated iC lesions. Torsional nystagmus following
      mesencephalic lesions may last for years and may help to distinguish rostral
      (riMLF) from caudal (iC) midbrain lesions.

PMID- 12499488
TI  - Medication adherence among HIV+ adults: effects of cognitive dysfunction and
      regimen complexity.
AB  - BACKGROUND: Although the use of highly active antiretroviral therapy in the
      treatment of HIV infection has led to considerable improvement in morbidity and
      mortality, unless patients are adherent to their drug regimen (i.e., at least 90
      to 95% of doses taken), viral replication may ensue and drug-resistant strains of
      the virus may emerge. METHODS: The authors studied the extent to which
      neuropsychological compromise and medication regimen complexity are predictive of
      poor adherence in a convenience sample of 137 HIV-infected adults. Medication
      adherence was tracked through the use of electronic monitoring technology (MEMS
      caps). RESULTS: Two-way analysis of variance revealed that neurocognitive
      compromise as well as complex medication regimens were associated with
      significantly lower adherence rates. Cognitively compromised participants on more
      complex regimens had the greatest difficulty with adherence. Deficits in
      executive function, memory, and attention were associated with poor adherence.
      Logistic regression analysis demonstrated that neuropsychological compromise was
      associated with a 2.3 times greater risk of adherence failure. Older age (>50
      years) was also found to be associated with significantly better adherence.
      CONCLUSIONS: HIV-infected adults with significant neurocognitive compromise are
      at risk for poor medication adherence, particularly if they have been prescribed
      a complex dosing regimen. As such, simpler dosing schedules for more cognitively
      impaired patients might improve adherence.

PMID- 12499491
TI  - Visual hallucinations in PD.

PMID- 12499492
TI  - A severe variant of childhood ataxia with central hypomyelination/vanishing white
      matter leukoencephalopathy related to EIF21B5 mutation.
AB  - Childhood ataxia with central hypomyelination (CACH)/vanishing white matter (VWM)
      leukoencephalopathy is related to mutations in all five genes of the eukaryotic
      translation initiation factor (eIF2B). In a fatal infantile leukoencephalopathy,
      which the authors previously classified as a severe variant of CACH/VWM, a new
      homozygous missense mutation in the EIF2B5 gene was found. Abnormal decrease in
      blood uric acid and increase of erythrocyte guanosine 5'-diphosphate sugars found
      in two siblings may contribute to the explanation of this particularly severe
      condition.

PMID- 12499493
TI  - MRI shows abnormal white matter maturation in classical holoprosencephaly.
AB  - In an attempt to assess white matter maturation in holoprosencephaly (HPE), MRI
      scans of 47 patients with HPE were retrospectively reviewed. White matter
      maturation was delayed in 25/47 patients, including 24/29 patients with classic
      HPE who were </=12 months old at the time of imaging. Of interest, all six
      patients with the middle interhemispheric (MIH) variant of HPE had normal
      myelination, regardless of age. This study provides further evidence that the
      classic and MIH variants of HPE have different underlying causes.

PMID- 12499494
TI  - Improvement of diabetic autonomic gustatory sweating by botulinum toxin type A.
AB  - Fourteen diabetic subjects with gustatory sweating were treated by intracutaneous
      injections of botulinum toxin type A into the affected facial skin areas. In all
      subjects, sweating (measured by Minor starch iodine test) ceased within 4 days,
      with the maximal follow-up time lasting 24 weeks. This therapeutic approach,
      which could be used to reduce the severity of diabetic gustatory sweating,
      appears to be long lasting, adverse effect free, and minimally invasive.

PMID- 12499495
TI  - [(123)I]-FP-CIT-SPECT in the early diagnosis of PD presenting as exercise-induced
      dystonia.
AB  - Isolated foot dystonia following exercise is a rare manifestation of early PD. It
      may precede the onset of parkinsonism by years and can be clinically
      indistinguishable from familial exercise-induced dystonia. The authors present a
      patient with dystonic claudication where dopamine transporter SPECT using (123)I
      FP-CIT allowed early diagnosis of PD and enabled effective symptomatic treatment
      with a dopamine agonist.

PMID- 12499496
TI  - Bilateral subthalamic nucleus stimulation improves health-related quality of life
      in PD.
AB  - In order to assess the impact of bilateral subthalamic nucleus (STN) stimulation
      in PD on quality of life, the PD Quality of Life questionnaire was assessed in 60
      consecutive patients with PD before surgery and 12 months after surgery. All
      aspects of quality of life, including motor (+48%), systemic (+34%), emotional
      (+29%), and social (+63%) dimensions, significantly improved with long-term STN
      stimulation.

PMID- 12499497
TI  - Hallucinations and sleep-wake cycle in PD: a 24-hour continuous polysomnographic
      study.
AB  - Twenty-four-hour ambulatory polysomnography was performed in 20 patients with PD
      who were having visual hallucinations (12 men and 8 women, mean age 70 +/- 6
      years). Visual hallucinations were clearly related to daytime NREM sleep or
      nocturnal REM sleep in 33% of the instances. The data reinforce the hypothesis
      that neural mechanisms implicated in generating sleep and, in particular, in
      dream imagery play a role in the occurrence of visual hallucinations in PD.

PMID- 12499498
TI  - Minimal tissue damage after stimulation of the motor thalamus in a case of chorea
      acanthocytosis.
AB  - Autopsy findings are reported from a patient with chorea-acanthocytosis treated
      for 2 years by deep brain stimulation (DBS) of the motor thalamus. Postoperative
      testing showed a progressive improvement in axial truncal spasms. Although
      relatively high currents were used for 2 years in this patient, postmortem
      analysis showed minimal tissue damage in the vicinity of the electrode tip. It is
      concluded that DBS has little impact on the surrounding tissues.

PMID- 12499499
TI  - Cerebellar degeneration and autoimmunity to zinc-finger proteins of the
      cerebellum.
AB  - The serum of a patient with subacute cerebellar dysfunction was used to probe a
      cDNA expression library and isolate two genes: Zic1 (zinc-finger of the
      cerebellum) and Zic4. The patient had intrathecal synthesis of Zic antibodies,
      suggesting that the Zic proteins were autoantigens of the neurologic disorder.
      The Zic proteins are involved in cerebellar development and are reported as being
      preferentially expressed by medulloblastomas. It was found that the expression of
      Zic proteins is enriched in, but not limited to, medulloblastomas and primitive
      neuroectodermal tumors.

PMID- 12499500
TI  - Corticospinal excitability in human sleep as assessed by transcranial magnetic
      stimulation.
AB  - The excitability of the corticospinal system was studied in 23 healthy subjects
      in sleep stages NREM2, NREM4, REM, and wakefulness using transcranial magnetic
      stimulation. Assessment of motor thresholds, stimulus-response curves, and
      latencies of motor evoked potentials shows activation of the fast-conducting
      corticospinal fibers in all sleep stages and a neuronal recruitment pattern
      similar to wakefulness, however, at a lower level of excitability and with
      significant differences between sleep stages.

PMID- 12499501
TI  - Gabapentin in late-onset poststroke seizures.
AB  - Stroke is a frequent cause of epileptic seizures (ES) in adults. The authors
      evaluated the long-term efficacy and tolerability of gabapentin (900 to 1,800
      mg/day) in 71 patients with a first poststroke late ES during a mean follow-up
      time of 30 months. ES recurred in 18.3% of the patients and side effects were
      noted in 27 cases (38%), but only two (2.8%) required discontinuation or early
      withdrawal. Gabapentin monotherapy was useful and safe for late poststroke ES.

PMID- 12499502
TI  - CNS angiitis in graft vs host disease.
AB  - Graft-vs-host disease (GVHD) is a potentially treatable cause of progressive
      neurologic decline after bone marrow transplantation (BMT). The authors present
      histologic confirmation of CNS granulomatous angiitis in a child with chronic
      GVHD after BMT. Since cranial MRI showed only nonspecific findings, CNS
      vasculitis associated with GVHD after BMT may be underdiagnosed.

PMID- 12499503
TI  - Similar binding to glutamate receptors by Rasmussen and partial epilepsy
      patients' sera.
AB  - Immunoreactivity of sera from patients with Rasmussen encephalitis (RE) and
      patients with partial epilepsy (PE) was analyzed by immunohistoblot on rat brain
      sections and the staining pattern compared with that obtained with antibodies to
      a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and NMDA receptors.
      Staining for anti-glutamate receptor 3 (GluR3) was found in 82% of patients with
      RE and 64% of patients with PE. Histoblot analysis showed a positive staining in
      GluR3- and NMDA-specific regions of rat brain, providing a comprehensive CNS
      immunolocalization.

PMID- 12499505
TI  - Hypersomnia in MS.

PMID- 12499504
TI  - SPG3A: An additional family carrying a new atlastin mutation.
AB  - The authors report on a novel frameshift mutation (c.1688insA) in the SPG3A gene
      resulting in premature translation termination of the gene product atlastin.
      These data add a new variant to the second disease gene in autosomal dominant
      hereditary spastic paraplegia (ADHSP) and lend definitive support to its
      causative role. By combining direct testing of SPAST and SPG3A, at least 50% of
      ADHSP families can now receive appropriate genetic diagnosis.

PMID- 12499506
TI  - Transient cerebral white matter lesions in a patient with connexin 32 missense
      mutation.

PMID- 12499507
TI  - Fine-needle, negative-pressure lumbar puncture: a safe technique for collecting
      CSF.

PMID- 12499508
TI  - Hereditary neuropathy with liability to pressure palsies in a toddler.

PMID- 12499509
TI  - Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics.

PMID- 12499510
TI  - Isolated weakness of index finger due to small cortical infarction.

PMID- 12499511
TI  - Is there a neurologist on this flight?

PMID- 12499512
TI  - Alopecia induced by dopamine agonists.

PMID- 12499513
TI  - Early symptom progression rate is related to ALS outcome: a prospective
      population-based study.

PMID- 12499514
TI  - Hematoma causing cortical hand.

PMID- 12499515
TI  - Severe neurologic complications after hematopoietic (peripheral blood) stem cell
      transplantation in children.

PMID- 12499516
TI  - Firsthand learning through intent participation.
AB  - This article examines how people learn by actively observing and "listening-in"
      on ongoing activities as they participate in shared endeavors. Keen observation
      and listening-in are especially valued and used in some cultural communities in
      which children are part of mature community activities. This intent participation
      also occurs in some settings (such as early language learning in the family) in
      communities that routinely segregate children from the full range of adult
      activities. However, in the past century some industrial societies have relied on
      a specialized form of instruction that seems to accompany segregation of children
      from adult settings, in which adults "transmit" information to children. We
      contrast these two traditions of organizing learning in terms of their
      participation structure, the roles of more- and less-experienced people,
      distinctions in motivation and purpose, sources of learning (observation in
      ongoing activity versus lessons), forms of communication, and the role of
      assessment.

PMID- 12499517
TI  - Diary methods: capturing life as it is lived.
AB  - In diary studies, people provide frequent reports on the events and experiences
      of their daily lives. These reports capture the particulars of experience in a
      way that is not possible using traditional designs. We review the types of
      research questions that diary methods are best equipped to answer, the main
      designs that can be used, current technology for obtaining diary reports, and
      appropriate data analysis strategies. Major recent developments include the use
      of electronic forms of data collection and multilevel models in data analysis. We
      identify several areas of research opportunities: 1. in technology, combining
      electronic diary reports with collateral measures such as ambulatory heart rate;
      2. in measurement, switching from measures based on between-person differences to
      those based on within-person changes; and 3. in research questions, using diaries
      to (a) explain why people differ in variability rather than mean level, (b) study
      change processes during major events and transitions, and (c) study interpersonal
      processes using dyadic and group diary methods.

PMID- 12499518
TI  - Linking brain and behavior in sleep-dependent learning and memory consolidation.

PMID- 12499519
TI  - A randomized comparison of direct stenting versus stenting with predilatation in
      native coronary artery disease: results from the multicentric Crosscut study.
AB  - Stenting without predilatation has become possible due to the availability of a
      new generation of flexible, low-profile, securely crimped, balloon-expandable
      stents. This study compared the feasibility, efficacy and cost-effectiveness of
      direct stenting (DS) to the standard predilatation technique (PS) using the
      premounted Crossflex LC stent (Cordis Corporation, Miami Lakes, Florida). The
      study is a randomized prospective multicenter evaluation including 271 patients
      (140 patients in the DS group and 131 patients in the PS group) with 1 or 2 de
      novo or restenotic lesions located in native coronary arteries. Procedural
      success was 98.9% and 98.7% in the DS and PS groups, respectively (p = NS);
      crossover to PS was required in 22/166 lesions (13.2%) enrolled in the DS group
      because of inability to cross the target lesion without predilatation.
      Nonsignificant reductions in procedural time (-10.5%), fluoroscopy time (-4.7%)
      and amount of contrast (-3.8%) were observed in the DS group in comparison to the
      PS group. The number of balloons used (-76.6%) and the global cost of the
      procedure (-18.8%) were significantly lower in the DS group (p < 0.01 for both
      comparisons). After 6 months, no differences were observed in the restenosis rate
      between the two groups (22.0% for DS group versus 18.1% for PS group; p = NS) and
      in the incidence of major adverse clinical events (5.0% for DS group versus 3.0%
      for PS group; p = NS). Direct stenting is safe and feasible for the treatment of
      lesions in native coronary arteries and obtains a significant reduction in
      procedural cost, mainly due to the lower number of balloons used. Clinical and
      angiographic results at 6 months are comparable to those obtained after a
      conventional predilatation-stenting strategy.

PMID- 12499520
TI  - Miniaturization of the equipment for percutaneous coronary interventions: a
      prospective study in 1,200 patients.
AB  - The aim of this prospective study was to analyze the technical feasibility,
      success rate and special complications of percutaneous coronary interventions
      (PCI) using a newly released 5 French (Fr) guiding catheter with an inner
      diameter of 0.058 . The study was performed in 1,200 consecutive patients
      subjected to coronary angioplasty. In 92% of the patients, the intervention was
      started with a 5 Fr catheter; in 8% of the patients, a 6 or 7 Fr catheter was
      used. In 5% of the 1,105 patients, the guiding catheter had to be changed during
      PCI from 5 Fr to a 6 or 7 Fr catheter. In 92% of the patients, the intervention
      was successfully performed using a 5 Fr catheter. In 3%, the overall success rate
      was 95% after changing the guiding catheter. Predictors of procedural failure
      with the 5 Fr guiding catheter were type C lesion morphology and a diameter
      stenosis of 99% and 100%. The success rate was 90% in acute functional occlusions
      and 63% in chronic total occlusions (CTO). In CTOs, predictors of procedural
      failure of the recanalizations using 5 Fr guiding catheters were sidebranch at
      the point of the total occlusion, complex lesion morphology type C and abrupt
      morphology of the occlusion. This study confirms that PCI was technically
      feasible using a 5 Fr guiding catheter in the majority of consecutive patients
      (success rate: 92%). There were significant differences in the success rate
      depending on the lesion type and the diameter stenosis.

PMID- 12499521
TI  - The smaller they come.

PMID- 12499522
TI  - A novel percutaneous technique for accessing the normal pericardium: a single
      center successful experience of 53 porcine procedures.
AB  - Recently, the pericardial space has been under consideration as an ideal site for
      prevention and treatment of coronary artery and heart disease. Historically, safe
      percutaneous entry has not been possible to sample or remove pericardial fluids
      for diagnostic purposes or to employ therapeutic agents in the absence of a
      sizable pericardial effusion. A non-surgical percutaneous approach to permit
      rapid access to the normal or minimally effused pericardial space holds high
      potential for considerable diagnostic and therapeutic utility. This study
      examines the utility of the PerDUCER  pericardial access device, a simplistic
      approach to permit percutaneous access to the normal, minimal or diseased
      pericardial space, in a large series of animals (swine). The PerDUCER , inserted
      through the introducer sheath in a sub-xiphoid position, allowed capture and
      delivery of the intrapericardial guidewire into the pericardial space in all
      animals. The procedure was well tolerated by all animals and exhibited no signs
      of significant adverse hemodynamic effects. Twelve animals were sacrificed
      immediately after the experiment, while 41 animals were sacrificed 28 days after
      the procedure. Histologic examination showed no occurrence of epicardial vessel
      or myocardial damage. In addition, no late complications were found related to
      pericardial access with the PerDUCER . This initial experiment demonstrates that
      the PerDUCER  provides an efficient, safe and effective technique to gain
      pericardial access in the normal or minimal pericardial space to obtain
      diagnostic sampling of the pericardial fluids and renders local intrapericardial
      delivery of therapeutic agents a possibility.

PMID- 12499523
TI  - Impact of gender on the incidence and outcome of contrast-induced nephropathy
      after percutaneous coronary intervention.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is a recognized complication after
      percutaneous interventions (PCI). We sought to determine the impact of gender on
      incidence and clinical outcome of CIN. METHODS AND RESULTS: Of a total 8,628
      patients who underwent PCI, there were 1,431 (16.5%) who developed CIN (defined
      as > 25% rise in creatinine after PCI). Patients were followed clinically for one
      year. CIN was present in 23.6% of female versus 17.4% of male patients (p <
      0.0001). Multivariate analysis showed that female gender (OR = 1.4, 95% CI = 1.25
      1.60; p < 0.0001), pre-PCI chronic renal failure (CRF) (OR= 1.8, 95% CI = 1.53
      2.10, p < 0.0001), diabetes mellitus (OR = 1.5, 95% CI = 1.34 1.70; p < 0.0001),
      age (OR = 1.01, 95% CI = 1.01 1.02, p < 0.0001), and hypertension (OR = 1.2, 95%
      CI = 1.06 1.36, p = 0.0035) were independent predictors of CIN. Clinical outcomes
      after CIN were examined in patients with or without CRF. Among patients without
      CRF who developed CIN, females (n = 465) had higher rates of one-year mortality,
      and MACE comparing to males (n = 710) without CRF (14% vs. 10% mortality, 36% vs.
      30% MACE; p = 0.05 and 0.06, respectively). In patients with CRF who developed
      CIN, we found no significant gender differences in one-year clinical events (37%
      vs. 36% mortality, 42% vs. 45% MACE; p = 0.8 and 0.6, respectively). By
      multivariate analysis only baseline CRF, diabetes, age, functional NYHA IV class
      were identified as independent predictors of one-year mortality in patients with
      CIN after PCI. CONCLUSIONS: Female gender is an independent predictor of CIN
      development after PCI and a marker of worse 1-year mortality after CIN in
      patients without baseline CRF. After CIN is developed, pre-PCI CRF, diabetes
      mellitus, age, severe heart failure (not gender) are independent predictors of
      one-year mortality.

PMID- 12499524
TI  - Radiocontrast nephropathy: a time for affirmative action.

PMID- 12499525
TI  - Transcatheter closure of patent ductus arteriosus in Chinese adults: immediate
      and long-term results.
AB  - BACKGROUND: Transcatheter closure of patent ductus arteriosus (PDA) has been
      established as a safe and effective treatment for pediatric patients. However,
      long-term experience in adults remains limited. Therefore, our purpose is to
      report our experience with this approach in Chinese adults. METHODS: Twenty-five
      patients (mean age, 34 years) who underwent transcatheter closure of PDA in a
      tertiary cardiology center in Hong Kong were recruited. RESULTS: The mean PDA
      diameter measured by angiogram was 3.1 mm (range, 1.3 6.6 mm) and the mean
      pulmonary-to-systemic shunt was 1.65 (range, 1.3 1.8). All procedures were
      performed under local anesthesia. The average procedure and fluoroscopy times
      were 54   14 minutes and 14   4 minutes, respectively. The mean period of
      hospitalization was 4 days (range, 3 5 days). Immediate, one-month and late
      success rates were 96%, 92% and 84%, respectively. CONCLUSIONS: Percutaneous
      closure of PDA in adults is a safe and feasible procedure. It should be a
      reasonable alternative for adult patients who are either not fit for open-chest
      surgery or who prefer a less invasive approach.

PMID- 12499526
TI  - The prognostic value of QT dispersion in patients presenting with acute
      neurological events.
AB  - QT dispersion (QTD) reflects heterogeneity of myocardial repolarization, which is
      modulated by the central nervous system. Previous studies have shown increased
      QTD to be a predictor of adverse outcomes in various cardiac states. The
      objective of this study was to determine the significance of QTD in patients
      hospitalized with cerebrovascular accidents (CVA) and transient ischemic
      accidents (TIA). We studied 140 consecutive patients (72   years old, 48% male)
      admitted to our institution with neurologic events from January 1998 to April
      1998. QTD was calculated from admission electrocardiogram as the difference
      between maximum and minimum QT intervals in at least 11 of 12 leads. Three
      separate instruments (NIH Stroke Scale, Barthel Index and Modified Rankin Scale)
      were used to assess functional status on discharge. QTD was higher in patients
      with intercerebral hemorrhage as compared to CVA and TIA (70   15 msec versus 53 
      27 msec versus 48   31 msec, respectively; p = 0.03). Increasing QTD was
      associated with lower functional outcomes on all 3 scales (all p < 0.05) and with
      higher mortality (p = 0.02). QTD was higher in patients with congestive heart
      failure (80   43 msec versus 47   24 msec; p = 0.006) and with carotid disease
      (59   32 msec versus 46   27 msec; p = 0.045) as compared to those without. On
      multivariate analysis, other independent predictors of worse outcome were QTD
      (odds ratio, 1.35; 95% confidence interval, 1.08 1.68) and a trend toward age
      (odds ratio, 1.07; 95% confidence interval, 0.99 1.16). On age-adjusted logistic
      regression, mortality increased by odds ratio of 1.28 and 95% confidence interval
      of 1.02 1.61 for every 10 msec increase in QTD. QTD is an independent predictor
      of functional outcome and mortality following acute neurological events. In this
      setting, QTD reflects neurological injury as well as underlying heart disease.

PMID- 12499527
TI  - Thrombectomy with rescue percutaneous thrombectomy catheter: our initial
      experience.
AB  - Plaque rupture and subsequent thrombus formation inside the coronary arteries has
      been known for years. Mechanical devices have been used for the extraction or
      dissolution of thrombus inside the coronary arteries. This report illustrates the
      use of the Rescue Percutaneous Thrombectomy Catheter in a right coronary artery
      loaded with thrombus. Following thrombectomy, the stenosis in the artery was well
      delineated. Successful balloon angioplasty was performed, which resulted in TIMI
      3 flow and no distal embolization. Rescue Percutaneous Thrombectomy Catheter has
      been successfully used in the setting of acute myocardial infarction. The present
      case illustrates that the Rescue Percutaneous Thrombectomy Catheter can be used
      for removing thrombus even one month after acute myocardial infarction.

PMID- 12499528
TI  - Acute stent recoil in the left main coronary artery treated with additional
      stenting.
AB  - We report a case of acute stent recoil occurring after the stenting of an ostial
      left main coronary artery lesion. The marked recoil after high-pressure balloon
      inflation confirmed that the radial force of the first stent was unable to ensure
      vessel patency. The addition of a second stent provided the necessary support to
      achieve a good final result. This case illustrates a possible complication of
      aorto-ostial angioplasty that could be treated with double stenting.

PMID- 12499529
TI  - Triple wire technique for a bifurcation lesion and a subtotal occlusive lesion.
AB  - In a critical distal right coronary artery bifurcation lesion, the proximal
      course of the posterior descending artery was also subtotally occluded. The
      posterior descending artery gave rise to a small sidebranch just before the
      occlusion. In the subsequent revascularization procedure, the bifurcation lesion
      was double-wired. One wire was placed in the postero-lateral branch, and another
      wire was intended for placement in the posterior descending artery, but it
      repeatedly selected the sidebranch despite multiple shapings of the wire tip.
      While the second wire was deliberately kept in the sidebranch, a third wire was
      used and crossed the occlusive lesion without much difficulty. The second wire
      was then withdrawn and the revascularization procedure proceeded in the usual
      manner. The positioning of the second wire in the sidebranch significantly
      shortened the procedure.

PMID- 12499530
TI  - Successful transradial coronary angioplasty and stenting using a self-expandable
      RADIUS stent to the anomalous left main coronary artery.
AB  - Stenting of anomalous coronary artery is technically challenging both from the
      femoral and radial approaches because of difficulty in cannulating the artery by
      the guiding catheters with enough back-up support for delivering the stent. We
      report the first case in the literature of transradial coronary angioplasty and
      stenting to an anomalous left main coronary artery originating from the right
      sinus of Valsalva. Left Amplatz guidance from the radial approach provided an
      adequate platform to advance the stent using a dummy guidewire technique, and a
      self-expandable RADIUS stent was successfully deployed in a tortuous lesion of
      the anomalous artery.

PMID- 12499531
TI  - Extensive dissection requiring multiple stents following balloon angioplasty for
      non-specific aorto-arteritis.
AB  - Discrete stenoses of the thoraco-abdominal aorta in non-specific aorto-arteritis
      are considered favorable lesions for balloon angioplasty characterized by good
      results without major complications. Herein, we describe one such case
      manifesting with severe hypertension, left ventricular dysfunction and congestive
      heart failure treated by angioplasty. Balloon dilatation, however, resulted in
      extensive dissection requiring implantation of two Wallstents. Over a follow-up
      of one year, hypertension remained under good control with fewer drugs and
      symptom relief was maintained. Left ventricular ejection fraction improved from
      35% to 61%.

PMID- 12499532
TI  - Changing of the guard.

PMID- 12499533
TI  - Physical aspects of protein crystal growth investigated with the Advanced Protein
      Crystallization Facility in reduced-gravity environments.
AB  - The physicochemical aspects of protein crystallization in reduced-gravity
      environments ( micro g) have been investigated with the Advanced Protein
      Crystallization Facility during six space missions. This review summarizes the
      results, dealing with the mechanisms of nucleation and crystal growth and with
      the quality of the crystals that were obtained under reduced gravity as well as
      under normal gravity on earth. Statistical analyses of the experimental data
      strongly support the fact that micro g has a positive effect on crystallization
      and on crystal quality. A comparison of experiments and theories of protein
      crystallization in reduced-gravity environments is presented. Recommendations for
      improving the performance of protein crystallization experiments in micro g and
      on earth are discussed.

PMID- 12499534
TI  - Structure of the N-terminal domain of human FKBP52.
AB  - FKBP52 is a member of the FK506-binding protein family (FKBPs). The N-terminal
      domain of FKBP52 (FKBP52-N; residues 1-140) is responsible for peptidyl-prolyl
      isomerase activity and binding of FK506. Here, the crystal structure of FKBP52-N
      has been determined by molecular replacement to 2.4 A. FKBP52-N is defined by a
      six-stranded antiparallel beta-sheet wrapping with a right-handed twist around a
      short alpha-helix, an architecture similar to that of FKBP12. FKBP52-N is able to
      bind FK506 in a similar way to FKBP12. The variability in two loop regions
      (residues 70-76 and 108-127) is the principal reason for the specificity
      differences between FKBP52-N and FKBP12. The Pro120 change corresponding to Gly89
      in FKBP12 limits the conformational adaptation between the loop (residues 108
      127) and FK506 and decreases the FK506 affinity, while the Lys121 substitution
      corresponding to Ile90 of FKBP12 destroys a key interaction between FKBP52-N and
      calcineurin. It can be inferred from the locations of strictly conserved amino
      acids in the polypeptide chain that the maintenance of the overall conformation
      of the PPIase domains of FKBPs is essential for the PPIase activity. The N
      terminal region and beta-sheets of FKBP52-N forms a hydrophobic patch which may
      be responsible for the binding of target proteins such as dynein or PAHX.

PMID- 12499535
TI  - Structure and catalytic mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate
      (MECDP) synthase, an enzyme in the non-mevalonate pathway of isoprenoid
      synthesis.
AB  - Precursors for isoprenoid synthesis are essential in all organisms. These
      compounds are synthesized by one of two known routes: the well characterized
      mevalonate pathway or a recently discovered non-mevalonate route which is used in
      many bacteria and human pathogens. Since the second pathway is both vital and
      unlike any found in humans, enzymes catalysing reactions along this synthetic
      route are possible drug targets. The structure of one such enzyme from the
      thermophilic bacterium Thermus thermophilus has been solved to high resolution in
      the presence of substrate and with a substrate analogue. Enzyme co-crystallized
      with substrate shows only one product, cytosine monophosphate (CMP), in the
      active site. At the high resolution of the refinement (1.6 A) the positions and
      coordination of the magnesium ions in the active site are clearly seen.

PMID- 12499536
TI  - Is the bond-valence method able to identify metal atoms in protein structures?
AB  - The proper assignment of metal ions in X-ray structures of proteins is not always
      easy, but in many cases this knowledge can be important, e.g. for an
      understanding of enzyme mechanism. In this publication, the bond-valence approach
      is assessed critically. A simplified version, the calcium bond-valence sum
      (CBVS), is proposed for the convenient analysis of the geometric environment of
      potential sites with a view to metal-ion assignment. The bond-valence approach is
      found to be more reliable for structures determined from high-resolution data
      (1.5 A or better).

PMID- 12499537
TI  - Automated main-chain model building by template matching and iterative fragment
      extension.
AB  - An algorithm for the automated macromolecular model building of polypeptide
      backbones is described. The procedure is hierarchical. In the initial stages,
      many overlapping polypeptide fragments are built. In subsequent stages, the
      fragments are extended and then connected. Identification of the locations of
      helical and beta-strand regions is carried out by FFT-based template matching.
      Fragment libraries of helices and beta-strands from refined protein structures
      are then positioned at the potential locations of helices and strands and the
      longest segments that fit the electron-density map are chosen. The helices and
      strands are then extended using fragment libraries consisting of sequences three
      amino acids long derived from refined protein structures. The resulting segments
      of polypeptide chain are then connected by choosing those which overlap at two or
      more C(alpha) positions. The fully automated procedure has been implemented in
      RESOLVE and is capable of model building at resolutions as low as 3.5 A. The
      algorithm is useful for building a preliminary main-chain model that can serve as
      a basis for refinement and side-chain addition.

PMID- 12499538
TI  - Automated side-chain model building and sequence assignment by template matching.
AB  - An algorithm is described for automated building of side chains in an electron
      density map once a main-chain model is built and for alignment of the protein
      sequence to the map. The procedure is based on a comparison of electron density
      at the expected side-chain positions with electron-density templates. The
      templates are constructed from average amino-acid side-chain densities in 574
      refined protein structures. For each contiguous segment of main chain, a matrix
      with entries corresponding to an estimate of the probability that each of the 20
      amino acids is located at each position of the main-chain model is obtained. The
      probability that this segment corresponds to each possible alignment with the
      sequence of the protein is estimated using a Bayesian approach and high
      confidence matches are kept. Once side-chain identities are determined, the most
      probable rotamer for each side chain is built into the model. The automated
      procedure has been implemented in the RESOLVE software. Combined with automated
      main-chain model building, the procedure produces a preliminary model suitable
      for refinement and extension by an experienced crystallographer.

PMID- 12499539
TI  - Three-dimensional structure of homodimeric cholesterol esterase-ligand complex at
      1.4 A resolution.
AB  - The three-dimensional structure of a Candida cylindracea cholesterol esterase
      (ChE) homodimer (534 x 2 amino acids) in complex with a ligand of proposed
      formula C(23)H(48)O(2) has been determined at 1.4 A resolution in space group P1
      using synchrotron low-temperature data. The structure refined to R = 0.136 and
      R(free) = 0.169 and has revealed new stereochemical details in addition to those
      detected for the apo- and holo-forms at 1.9 and 2.0 A resolution, respectively
      [Ghosh et al. (1995), Structure, 3, 279-288]. The cholesterol esterase structure
      is a dimer with four spatially separated interfacial contact areas and two
      symmetry-related pairs of openings to an internal intradimer cavity. Hydrophobic
      active-site gorges in each subunit face each other across a central interfacial
      cavity. The ChE subunits have carbohydrate chains attached to their Asn314 and
      Asn351 residues, with two ordered N-acetyl-D-glucosoamine moieties visible at
      each site. The side chains of 14 residues have two alternative conformations with
      occupancy values of 0.5 +/- 0.2. For each subunit the electron density in the
      enzyme active-site gorge is well modeled by a C(23)-chain fatty acid.

PMID- 12499540
TI  - Locating the anomalous scatterer substructures in halide and sulfur phasing.
AB  - Improved data quality now makes it feasible to exploit the weak anomalous signal
      derived only from the sulfurs inherent to the protein or in particular from
      halide ions incorporated by soaking. The latter technique requires the location
      of a high number of partially occupied halide sites. This number appears to be
      roughly proportional to the exposed protein surface. This paper explores the
      application of dual-space ab initio methods as implemented in the program SHELXD
      to the location of substructures of sulfur in SAD experiments, bromide in SAD and
      MAD experiments and iodide using SAD and SIRAS to determine the anomalous-atom
      substructure. Sets of atoms consistent with the Patterson function were generated
      as a starting point for the dual-space recycling procedure in SHELXD. The
      substructure is then expanded to the full structure by maximum-likelihood phasing
      with SHARP and density modification with the program DM. Success in the location
      of the substructures and subsequent phasing depends critically on the quality of
      the data and on the extent of the anomalous signal. This varies with each crystal
      and soak, but for the same crystal the significance of the anomalous signal was
      found to be highly sensitive to the redundancy of the intensity measurements,
      which in some cases made all the difference. This is illustrated by the
      determination of the previously unknown structure of repeat 11 of the human
      mannose-6-phosphate/insulin-like growth factor II receptor (Man6P/IGFII
      receptor), with 310 amino acids in the asymmetric unit, which was phased by
      soaking the crystals in a cryoprotectant solution containing halide anions.

PMID- 12499541
TI  - Near-atomic resolution crystal structure of an A-DNA decamer d(CCCGATCGGG):
      cobalt hexammine interaction with A-DNA.
AB  - The structure of the DNA decamer d(CCCGATCGGG) has been determined at 1.25 A
      resolution. The decamer crystallized in the tetragonal space group P4(3)2(1)2,
      with unit-cell parameters a = b = 44.3, c = 24.8 A and one strand in the
      asymmetric unit. The structure was solved by the molecular-replacement method and
      refined to R(work) and R(free) values of 16.3 and 18.5%, respectively, for 5969
      reflections. The decamer forms the A-form DNA duplex, with the abutting crystal
      packing typical of A-DNA. The crystal packing interactions seem to distort the
      local conformation: A5 adopts the trans/trans conformation for the torsion angles
      alpha and gamma instead of the usual gauche(-)/gauche(+) conformations, yielding
      G*(G.C) base triplets. The highly hydrated [Co(NH(3))(6)](3+) ion adopts a novel
      binding mode to the DNA duplex, binding directly to phosphate groups and
      connecting to N7 and O6 atoms of guanines by water bridges. Analysis of thermal
      parameters (B factors) shows that the nucleotides involved in abutting crystal
      packing are thermally more stable than other nucleotides in the duplex.

PMID- 12499542
TI  - Structure of Escherichia coli uridine phosphorylase at 2.0 A.
AB  - The 2.0 A crystal structure has been determined for Escherichia coli uridine
      phosphorylase (UP), an essential enzyme in nucleotide biosynthesis that catalyzes
      the phosphorolytic cleavage of the C-N glycosidic bond of uridine to ribose-1
      phosphate and uracil. The structure determination of two independent monomers in
      the asymmetric unit revealed the residue composition and atomic details of the
      apo configurations of each active site. The native hexameric UP enzyme was
      revealed by applying threefold crystallographic symmetry to the contents of the
      asymmetric unit. The 2.0 A model reveals a closer structural relationship to
      other nucleotide phosphorylase enzymes than was previously appreciated.

PMID- 12499543
TI  - A rapid method for assessing lipid:protein and detergent:protein ratios in
      membrane-protein crystallization.
AB  - A simple procedure for rapidly measuring lipid:protein ratios and detergent
      concentrations at different stages of the solubilization, purification and
      crystallization of membrane proteins has been developed. Fourier-transform
      infrared spectra recorded from 10 micro l aliquots of solution using a single
      bounce diamond-attenuated total reflectance apparatus exhibit characteristic
      bands arising from the vibrations of lipid, protein and detergent. Lipid:protein
      molar ratios as low as 5:1 (for a protein with a molecular weight of 300 kDa) are
      determined by comparing the ratio of the integrated intensity of the lipid ester
      carbonyl band near 1740 cm(-1) with the protein amide I band near 1650 cm(-1).
      Detergent concentrations at levels well below the critical micellar concentration
      of most detergents are determined by comparing the integrated intensities of the
      detergent vibrations, particularly in the 1200-1000 cm(-1) region, with a
      standard curve. Protein amide I band-shape analysis provides insight into the
      effects of detergents on protein secondary structure. The importance of
      monitoring detergent concentration changes during simple procedures, such as the
      concentration of a membrane protein by ultrafiltration, is demonstrated. This
      analytical tool has been used to rapidly establish protocols for minimizing lipid
      and detergent levels in solubilized membrane-protein samples.

PMID- 12499544
TI  - Atomic resolution structure of Erwinia chrysanthemi L-asparaginase.
AB  - An X-ray structure of L-asparaginase from Erwinia chrysanthemi (ErA) has been
      refined at 1 A resolution to an R factor of below 0.1, using data collected on a
      synchrotron source. With four molecules of the enzyme consisting of 327 amino
      acids each, this crystal contains one of the largest asymmetric units of a
      protein refined to date at atomic resolution. Previously, structures of ErA and
      of related enzymes from other bacterial sources have been refined at resolutions
      not exceeding 1.7 A; thus, the present structure represents a very significant
      improvement in the quality of the available models of these proteins and should
      provide a good basis for future studies of the conformational variability of
      proteins, identification of subtle conformational features and corroboration of
      the stereochemical libraries, amongst other things. L-Asparaginases, which are
      enzymes that catalyze the hydrolysis of L-asparagine to aspartic acid, have been
      used for over 30 y as therapeutic agents in the treatment of acute childhood
      lymphoblastic leukemia, although the details of the enzymatic reaction and
      substrate specificity have not yet been completely elucidated. This atomic
      resolution structure is a step in that direction.

PMID- 12499545
TI  - The refined atomic structure of carbonic anhydrase II at 1.05 A resolution:
      implications of chemical rescue of proton transfer.
AB  - Using synchrotron radiation and a CCD detector, X-ray data have been collected at
      100 K for the His64Ala mutant of human carbonic anhydrase II complexed with 4
      methylimidazole (4-MI) to a maximal 1.05 A resolution, allowing full anisotropic
      least-squares refinement. The refined model has a conventional R factor of 15.7%
      for all reflections. The C(alpha) coordinates of the model presented here have an
      r.m.s. deviation of 0.10 A relative to the previously determined structure at 1.6
      A resolution. Several amino-acid residues (six of the 255 observed) have been
      identified with multiple rotamer side-chain conformations. C, N and O atoms can
      be differentiated with selective electron-density map contouring. The estimated
      standard deviations for all main-chain non-H atom bond lengths and angles are
      0.013 and 0.030 A, respectively, based on unrestrained full-matrix least-squares
      refinement. This structure gives detailed information about the tetrahedrally
      arranged zinc ion coordinated by three histidine N atoms (His94 N(epsilon 2),
      His96 N(epsilon2) and His119 N(delta1)) and a water/hydroxide, the multiple
      binding sites of the proton chemical rescue molecule 4-MI and the solvent
      networks linking the zinc-bound water/hydroxide and 4-MI molecules. This
      structure presents the highest resolution structure of a carbonic anhydrase
      isozyme so far determined and adds to the understanding of proton-transfer
      processes.

PMID- 12499546
TI  - Thermostable xylanase from Thermoascus aurantiacus at ultrahigh resolution (0.89
      A) at 100 K and atomic resolution (1.11 A) at 293 K refined anisotropically to
      small-molecule accuracy.
AB  - Thermoascus aurantiacus xylanase is a thermostable enzyme which hydrolyses xylan,
      a major hemicellulose component of the biosphere. The crystal structure of this
      F/10 family xylanase, which has a triosephosphate isomerase (TIM) barrel
      (beta/alpha)(8) fold, has been solved to small-molecule accuracy at atomic
      resolution (1.11 A) at 293 K (RTUX) and at ultrahigh resolution (0.89 A) at 100 K
      (CTUX) using X-ray diffraction data sets collected on a synchrotron light source,
      resulting in R/R(free) values of 9.94/12.36 and 9.00/10.61% (for all data),
      respectively. Both structures were refined with anisotropic atomic displacement
      parameters. The 0.89 A structure, with 177 476 observed unique reflections, was
      refined without any stereochemical restraints during the final stages. The salt
      bridge between Arg124 and Glu232, which is bidentate in RTUX, is water-mediated
      in CTUX, suggesting the possibility of plasticity of ion pairs in proteins, with
      water molecules mediating some of the alternate arrangements. Two buried waters
      present inside the barrel form hydrogen-bond interactions with residues in
      strands beta2, beta3, beta4 and beta7 and presumably contribute to structural
      stability. The availability of accurate structural information at two different
      temperatures enabled the study of the temperature-dependent deformations of the
      TIM-barrel fold of the xylanase. Analysis of the deviation of corresponding
      C(alpha) atoms between RTUX and CTUX suggests that the interior beta-strands are
      less susceptible to changes as a function of temperature than are the alpha
      helices, which are on the outside of the barrel. betaalpha-loops, which are
      longer and contribute residues to the active-site region, are more flexible than
      alphabeta-loops. The 0.89 A structure represents one of the highest resolution
      structures of a protein of such size with one monomer molecule in the asymmetric
      unit and also represents the highest resolution TIM-barrel fold structure to
      date. It may provide a useful template for theoretical modelling studies of the
      structure and dynamics of the ubiquitous TIM-barrel fold.

PMID- 12499547
TI  - A new class of gadolinium complexes employed to obtain high-phasing-power heavy
      atom derivatives: results from SAD experiments with hen egg-white lysozyme and
      urate oxidase from Aspergillus flavus.
AB  - Seven gadolinium complexes are shown to be excellent compounds for the
      preparation of heavy-atom derivatives for macromolecular crystallography
      projects. De novo phasing has been carried out using single-wavelength anomalous
      diffraction (SAD) on a series of gadolinium-derivative crystals of two proteins:
      hen egg-white lysozyme and urate oxidase from Aspergillus flavus. Lysozyme
      derivative crystals were obtained by co-crystallizing the protein with the
      corresponding gadolinium complex at a concentration of 100 mM. Diffraction data
      were collected to a resolution of 1.7 A using Cu K(alpha) radiation from a
      rotating-anode generator, making use of the high anomalous signal of gadolinium
      at this wavelength. Urate oxidase derivative crystals were obtained by soaking
      native crystals in 100 mM gadolinium complex solutions. Diffraction data were
      collected to a resolution close to 3 A using X-rays at the Gd L(III) absorption
      edge, taking advantage of the sharp white line on that edge. For all urate
      oxidase derivative crystals and three of the lysozyme crystals, SAD phasing led
      to electron-density maps of very high quality, allowing unambiguous chain
      tracing. From this study, the binding effectiveness of the gadolinium complexes
      seems to be related to the nature of the precipitant used for crystallization.
      These gadolinium complexes represent a new class of high-phasing-power heavy-atom
      derivatives that may be used for high-throughput structure-determination
      projects.

PMID- 12499548
TI  - Structure of a yeast hypothetical protein selected by a structural genomics
      approach.
AB  - Yeast hypothetical protein YBL036C (SWISS-PROT P38197), initially thought to be a
      member of an 11-protein family, was selected for crystal structure determination
      since no structural or functional information was available. The structure has
      been determined independently by MIR and MAD methods to 2.0 A resolution. The MAD
      structure was determined largely through automated model building. The protein
      folds as a TIM barrel beginning with a long N-terminal helix, in contrast to the
      classic triose phosphate isomerase (TIM) structure, which begins with a beta
      strand. A cofactor, pyridoxal 5'-phosphate, is covalently bound near the C
      terminal end of the barrel, the usual active site in TIM-barrel folds. A single
      domain monomeric molecule, this yeast protein resembles the N-terminal domain of
      alanine racemase or ornithine decarboxylase, both of which are two-domain dimeric
      proteins. The yeast protein has been shown to have amino-acid racemase activity.
      Although selected as a member of a protein family having no obvious relationship
      to proteins of known structure, the protein fold turned out to be a well known
      and widely distributed fold. This points to the need for a more comprehensive
      base of structural information and better structure-modeling tools before the
      goal of structure prediction from amino-acid sequences can be realised. In this
      case, similarity to a known structure allowed inferences to be made about the
      structure and function of a widely distributed protein family.

PMID- 12499549
TI  - Crystals of trp repressor suitable for high-resolution neutron Laue diffraction
      studies.
AB  - Crystallization and preliminary neutron-diffraction measurements of wild-type
      variant Val58-->Ile of the Escherichia coli trp repressor are reported. A vapor
      diffusion chamber suitable for initial protein-solution Volumes in the range 0.2
      0.5 ml was used to grow cube-shaped crystals with edge dimensions in the range
      0.8-1.4 mm. Neutron Laue measurements to a nominal resolution of 2.1 A were
      recorded from a D(2)O-exchanged crystal using the LADI instrument at ILL. These
      results demonstrate that it will be possible for the first time to obtain a full
      atom neutron structural model of a DNA-binding protein plus its associated
      solvent. Direct observation of hydrogen bonding between protein and solvent
      should enhance understanding of the role of solvent in protein-DNA recognition.

PMID- 12499550
TI  - Crystallization and preliminary X-ray analysis of Alicyclobacillus acidocaldarius
      endoglucanase CelA.
AB  - Crystallization of a family 9 beta-1,4-glucanase from the thermoacidophilic
      bacterium Alicyclobacillus acidocaldarius CelA is reported. Thin plates can be
      obtained by hanging-drop vapour-diffusion crystallization in high concentrations
      (60%) of MPD. These crystals are unusual in that they do not bind the dye IZIT in
      the mother liquor and do not appear to dissolve in water after three weeks or in
      the storage buffer after 2 d. The crystals diffract weakly and the diffraction
      pattern is compatible with crystal disorder in one direction. After testing
      several crystals at the ESRF beamlines ID14-1 and ID14-2, a crystal was found
      which gave ordered diffraction in all directions. A full data set was collected
      to 3.0 A resolution, which allowed unambiguous determination of the space group
      as P2(1)2(1)2 and the unit-cell parameters as a = 85, b = 129.7, c = 48.6 A.
      Initial promising results from molecular-replacement searches are reported.

PMID- 12499551
TI  - Crystallization and X-ray diffraction analysis of an all-RNA U39C mutant of the
      minimal hairpin ribozyme.
AB  - The hairpin ribozyme is a naturally occurring catalytic RNA composed of two helix
      loop-helix domains, A and B, that dock to form the biologically active enzyme.
      Previously, the crystal structure of the hairpin has been solved as a four-way
      helical junction that incorporated the U1A protein as an artificial crystal
      packing motif [Rupert & Ferre-D'Amare (2001), Nature (London), 410, 780-786].
      Here, the crystallization of a minimal junctionless hairpin ribozyme 64-mer is
      reported in the absence of protein. Crystals grow in space group P6(1)22, with
      unit-cell parameters a = 93.1, c = 123.2 A. Complete diffraction data have been
      collected to 3.35 A resolution. Structural analysis should provide details of
      intermolecular RNA docking, including the ground-state conformations of the
      U(39)C mutation relevant to hairpin catalysis.

PMID- 12499552
TI  - Crystallization and preliminary crystallographic analysis of a partial
      extracellular fragment of a sperm membrane protein YWK-II/APPH related to the
      Alzheimer betaA4-amyloid precursor protein.
AB  - Crystals of a partial extracellular fragment of a human sperm membrane protein
      YWK-II/APPH have been grown at 291 K using PEG 4000 as precipitant. The
      diffraction pattern of the crystal extends to 2.8 A resolution at 100 K using Cu
      K(alpha) radiation. The crystals belong to space group P2(1)2(1)2(1), with unit
      cell parameters a = 46.009, b = 67.387, c = 149.241 A, alpha = beta = gamma = 90
      degrees. The presence of two molecules per asymmetric unit gives a crystal Volume
      per protein mass (V(M)) of 3.51 A(3) Da(-1) and a solvent content of 64.6% by
      Volume. A full set of X-ray diffraction data were collected to 2.8 A resolution
      from the native crystal.

PMID- 12499553
TI  - Expression, crystallization and preliminary X-ray analysis of isomaltulose
      synthase (PalI) from Klebsiella sp. LX3.
AB  - Isomaltulose synthase (PalI) catalyzes the hydrolysis of the alpha-1,2 bond
      between the glucose and fructose moieties of sucrose and the formation of alpha
      1,6 and alpha-1,1 bonds between the two components to produce isomaltulose (alpha
      D-glucosylpyranosyl-1,6-D-fructofranose) and trehalulose (alpha-D
      glucosylpyranosyl-1,1-D-fructofranose), respectively. The PalI protein has been
      overexpressed, purified and crystallized at 295 K using the hanging-drop vapour
      diffusion method. The crystals diffract to 2.2 A resolution using synchrotron
      radiation and belong to the orthorhombic space group P2(1)2(1)2(1), with unit
      cell parameters a = 59.239, b = 94.153, c = 111.294 A.

PMID- 12499554
TI  - Preliminary X-ray crystallographic analysis of tRNA pseudouridine 55 synthase
      from the thermophilic eubacterium Thermotoga maritima.
AB  - Thermotoga maritima TruB, an enzyme responsible for the formation of
      pseudouridine in tRNA, has been purified and crystallized by the hanging-drop
      vapour-diffusion method in 100 mM citrate pH 3.5, 200 mM Li(2)SO(4), 20%
      glycerol, 13% PEG 8000. Crystals display orthorhombic symmetry, with unit-cell
      parameters a = 47.39, b = 83.88, c = 98.72 A, and diffract to 2.0 A resolution
      using synchrotron radiation. A solution was obtained by molecular replacement
      using part of the recently published crystal structure of Escherichia coli TruB
      bound to a synthetic RNA.

PMID- 12499555
TI  - Crystallization of the GTP-dependent transcriptional regulator CodY from Bacillus
      subtilis.
AB  - CodY is a GTP sensor that represses transcription of early stationary phase and
      sporulation genes in Bacillus subtilis. As nutrients become limiting, GTP levels
      fall and CodY-mediated repression is relieved. Crystals of CodY have been grown
      in the presence and absence of GTP from sodium citrate buffered solutions
      containing lithium sulfate and diffraction data have been collected extending to
      3.5 A spacing.

PMID- 12499556
TI  - X-ray analysis of two antibiotic-synthesizing bacterial ester hydrolases:
      preliminary results.
AB  - Alpha-amino-acid ester hydrolases are multimeric enzymes of potential use in
      antibiotic production. Knowledge of their structure could help to engineer these
      enzymes into economically viable biocatalysts. The alpha-amino-acid ester
      hydrolases from Xanthomonas citri and Acetobacter turbidans have been
      crystallized. The X. citri enzyme crystallizes in a primitive monoclinic space
      group (unit-cell parameters a = 90.1, b = 125.8, c = 132.1 A, beta = 90.9 degrees
      ). The A. turbidans enzyme crystallizes in both a primitive orthorhombic (a =
      99.1, b = 104.9, c = 284.9 A) and a body-centred cubic space group with a = b = c
      = 342.2 A. From both enzymes, diffraction-quality crystals (resolution 3.0 A or
      better) were obtained. Data-collection statistics are reported for data sets from
      both enzymes.

PMID- 12499557
TI  - Jel44 monoclonal Fab fragment specific for HPr of the phosphoenolpyruvate:sugar
      phosphotransferase system of Escherichia coli and the complex of Jel44 Fab
      fragment with HPr: preparation, crystallization and preliminary crystallographic
      analysis.
AB  - Jel44 is a mouse monoclonal antibody specific for the histidine-containing
      phosphocarrier protein (HPr), a component of a sugar-transport system in
      Escherichia coli. Because Jel44 binding to HPr is dependent upon ionic strength
      and the enthalpic and entropic contributions do not vary over the temperature
      range 277-310 K, the complex is of great interest. A single crystal of the Jel44
      Fab fragment was obtained and diffracted X-rays to a maximum resolution of 4.6 A
      on an in-house X-ray source. The crystal belongs to space group P2(1), with unit
      cell parameters a = 68.6, b = 67.7, c = 105.5 A, beta = 96 degrees. Although
      crystals of the complex of Jel44 Fab fragment with HPr could not be fully
      characterized owing to suspected crystal twinning, it was encouraging that they
      diffracted X-rays to 2.5 A on an in-house X-ray source. It is thus foreseen that
      improvement of crystal quality will allow the complete solution of this novel
      structure.

PMID- 12499558
TI  - Crystallization and preliminary X-ray studies of thymus and activation-regulated
      chemokine (TARC).
AB  - Thymus and activation-regulated chemokine (TARC) is a CC chemokine that is most
      highly expressed in the thymus. TARC interacts primarily with the CCR4 receptor
      and to a lesser extent with the CCR8 receptor. Three different crystal forms of
      synthetically prepared TARC were grown in triclinic, hexagonal and tetragonal
      systems. The X-ray data for the triclinic crystals (unit-cell parameters a =
      56.46, b = 76.48, c = 88.37 A, alpha = 85.8, beta = 72.8, gamma = 70.0 degrees )
      extend to 1.85 A on a conventional radiation source. The hexagonal crystals
      diffracted to 2.2 A at a synchrotron-radiation source and belong to either space
      group P6(1)22 or P6(5)22, with unit-cell parameters a = 61.8, c = 315. A. The
      tetragonal crystals diffracted to about 5 A at a synchrotron-radiation source and
      had approximate unit-cell parameters a = b = 47.7, c = 58.2 A.

PMID- 12499559
TI  - Crystallization and preliminary X-ray crystallographic analysis of malonyl-CoA
      decarboxylase from Rhizobium leguminosarum bv. trifolii.
AB  - Malonyl-CoA decarboxylase (MCD), which catalyzes the conversion of malonyl-CoA to
      acetyl-CoA, is an evolutionarily distinct and highly conserved enzyme. MCD does
      not share sequence homology with other known decarboxylases, while the enzymes
      from different species exhibit at least >30% sequence identity to each other. In
      order to provide a canonical structure of the enzyme for detailed study of its
      structure-function relationship, the MCD of Rhizobium leguminosarum bv. trifolii
      was overexpressed and crystallized. The crystals belong to the orthorhombic space
      group P2(1)2(1)2, with unit-cell parameters a = 133.45, b = 127.10, c = 66.37 A.
      The asymmetric unit is likely to contain two molecules of MCD (molecular weight
      of 51 418 Da), with a crystal Volume per protein weight (V(M)) of 2.69 A(3) Da(
      1) and a solvent content of about 54.3% by Volume. A native data set to 3.0 A
      resolution was obtained using a rotating-anode X-ray generator.

PMID- 12499560
TI  - SseA, a 3-mercaptopyruvate sulfurtransferase from Escherichia coli:
      crystallization and preliminary crystallographic data.
AB  - SseA, the translation product of the Escherichia coli sseA gene, is a 31 kDa
      protein endowed with 3-mercaptopyruvate:cyanide sulfurtransferase activity in
      vitro. As such, SseA is the prototype of a sulfurtransferase subfamily
      distinguished from the better known rhodanese sulfurtransferases, which display
      thiosulfate:cyanide sulfurtransferase activity. The physiological role of the two
      homologous enzyme families, whose catalytic activity is centred on a reactive
      invariant cysteine, is a matter of debate. In this framework, the forthcoming
      crystal structure analysis of SseA will be based on the tetragonal crystal form
      (space group P4(1) or P4(3)) reported here, with unit-cell parameters a = b =
      150.2, c = 37.9 A.

PMID- 12499561
TI  - Crystallization and preliminary X-ray diffraction studies of Hje, a HolliDay
      junction resolving enzyme from Sulfolobus solfataricus.
AB  - HolliDay junction endonuclease (Hje) from Sulfolobus solfataricus is a resolving
      enzyme involved in cleaving specific sites on either side of recombinant four-way
      HolliDay junctions. The HJE gene from S. solfataricus was cloned from genomic DNA
      into the pET19b Escherichia coli expression vector and recombinant protein was
      expressed to high levels. Hje was purified using heat treatment, cation exchange
      and gel filtration. Hanging-drop crystallization trials yielded primitive
      hexagonal crystals which diffract to 2.4 A on a laboratory source. Systematic
      absences (only 00l = 6n present) and poor scaling in P622 indicate that the space
      group is P6(1) or its enantiomer. Failed attempts at molecular replacement using
      models of a related archaeal resolving enzyme, Hjc, raise the possibility of a
      difference in quaternary structure between Hjc and Hje, which may be responsible
      for differences in their activities.

PMID- 12499562
TI  - Crystallization and preliminary X-ray diffraction studies of a novel alcohol
      dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix.
AB  - A novel alcohol dehydrogenase enzyme has been cloned from the hyperthermophilic
      archaeon Aeropyrum pernix and overexpressed in Escherichia coli. This zinc
      containing enzyme has been crystallized by the sitting-drop vapour-diffusion
      method using PEG 600 as precipitant. The crystals diffract to 1.5 A resolution
      and belong to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters
      a = 100.7, b = 103.2, c = 67.5 A. The asymmetric unit contains two enzyme
      monomers. Two synchrotron data sets have been collected: one at a wavelength near
      the absorption edge of zinc and one at a remote wavelength. Three strong zinc-ion
      positions were visible in the anomalous Patterson map. Two additional weaker zinc
      ions have been identified by anomalous Fourier synthesis.

PMID- 12499563
TI  - Crystallographic characterization of the radixin FERM domain bound to the C
      terminal region of the human Na+/H+-exchanger regulatory factor (NHERF).
AB  - Radixin is a member of the ERM proteins, which cross-link plasma membranes and
      actin filaments. The N-terminal FERM domains of ERM proteins interact with
      Na(+)/H(+)-exchanger regulatory factors (NHERFs), which are PDZ-containing
      adaptor proteins, to modulate the ion-channel activity. Here, crystals of
      complexes between the radixin FERM domain and the C-terminal regions of NHERF and
      NHERF2 have been obtained. The crystals of the FERM-NHERF complex were found to
      belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 69.38 (2), b =
      146.27 (4), c = 177.76 (7) A. The crystal contains four complexes in the
      asymmetric unit. An intensity data set was collected to a resolution of 2.50 A.

PMID- 12499564
TI  - Crystallization and preliminary X-ray crystallographic studies of 3-deoxy-manno
      octulosonate cytidylyltransferase from Haemophilus influenzae.
AB  - The enzyme 3-deoxy-manno-octulosonate cytidylyltransferase (CMP-KDO synthetase;
      CKS) catalyzes the activation of 3-deoxy-manno-octulosonate (KDO) by forming CMP
      KDO. It is essential for the biosynthesis of lipopolysaccharides in Gram-negative
      bacteria and is a potential target for the discovery of antibacterial agents. L
      CKS from Haemophilus influenzae was overexpressed with a C-terminal hexahistidine
      tag in Escherichia coli and crystallized in the presence of the substrate KDO at
      297 K using PEG 4000 as a precipitant and ethylene glycol as an additive. The
      diffraction limit and spot shape of the native crystal could be improved
      significantly by dehydration/annealing. X-ray diffraction data were collected to
      2.5 A resolution from a native crystal. The crystals are orthorhombic, belonging
      to the space group P2(1)2(1)2(1), with unit-cell parameters a = 48.6, b = 83.1, c
      = 117.3 A. The presence of two monomers of recombinant L-CKS in the
      crystallographic asymmetric unit gives a reasonable V(M) of 2.05 A(3) Da(-1),
      with a solvent content of 40.0%.

PMID- 12499565
TI  - Crystallization and preliminary X-ray crystallographic analysis of
      tRNA(m1G37)methyltransferase from Haemophilus influenzae.
AB  - The enzyme tRNA(m(1)G37)methyltransferase (TrmD) catalyzes the transfer of a
      methyl group from S-adenosyl-L-methionine (AdoMet) specifically to guanosine at
      position 37 within a subset of tRNA species in bacteria. The modified guanosine
      is next to the anticodon and is important for the maintenance of the correct
      reading frame during translation. TrmD from Haemophilus influenzae with both N-
      and C-terminal tags was overexpressed in Escherichia coli and crystallized at 297
      K using sodium acetate as a precipitant. Native X-ray diffraction data were
      collected to 1.85 A resolution. The crystals are rhombohedral, belonging to the
      space group R32, with unit-cell parameters a = b = 98.05, c = 176.79 A, alpha =
      beta = 90, gamma = 120 degrees. The presence of one monomer of recombinant TrmD
      in the crystallographic asymmetric unit gives a V(M) of 3.07 A(3) Da(-1) and a
      solvent content of 59.9%.

PMID- 12499566
TI  - Crystallization and preliminary crystallographic analysis of T7 RNA polymerase
      elongation complex.
AB  - Stable transcription-elongation complexes consisting of T7 RNA polymerase
      (molecular mass 99 kDa) in association with a nucleic acid scaffold consisting of
      an 8 bp RNA-DNA hybrid and 10 bp of downstream DNA were assembled and
      crystallized by the sitting-drop vapour-diffusion technique under near
      physiological conditions. The crystals diffract beyond 2.6 A resolution and
      belong to space group P1, with unit-cell parameters a = 79.91, b = 84.97, c = 202
      A, alpha = 90.36, beta = 92.97, gamma = 109.94 degrees. An unambiguous molecular
      replacement solution was found using the C-terminal portion of the T7 RNA
      polymerase structure from the early initiation complex as a search model. Model
      building and structure refinement are now in progress.

PMID- 12499567
TI  - Preliminary crystallographic analysis of 3-chlorocatechol 1,2-dioxygenase of a
      new modified ortho-pathway from the Gram-positive Rhodococcus opacus 1CP grown on
      2-chlorophenol.
AB  - 3-Chlorocatechol 1,2-dioxygenase (3-ClC1,2DO), a key enzyme of a new modified
      ortho-pathway, was isolated from a variant of the Gram-positive bacterium
      Rhodococcus opacus 1CP utilizing 2-chlorophenol as the sole energy and carbon
      source via a 3-chlorocatechol branch of a modified ortho-pathway. 3-ClC1,2DO
      catalyzes the intradiol cleavage of 3-chlorocatechol. The enzyme contains Fe(III)
      ions essential to the catalytic activity; it is a homodimer with a molecular
      weight of about 58 kDa composed of two identical subunits in an (alphaFe)(2)-type
      quaternary structure. Its physicochemical properties are intermediate between
      those of the pyrocatechase from the ordinary pathway and those of the chloro
      pyrocatechase from the modified pathway described previously for this strain. 3
      ClC1,2DO was crystallized using the sitting-drop vapour-diffusion method. After 2
      d, prismatic crystals grew in 15% PEG 8000, 0.3 M magnesium acetate, 100 mM HEPES
      pH 7.5, 5% glycerol. X-ray diffraction data were collected from a frozen crystal
      to a maximum resolution of 2.0 A using 25% PEG 400 as cryoprotectant at the
      Elettra synchrotron source, Trieste, Italy, at a wavelength of 1.01 A using a MAR
      CCD detector. The crystals belong to space group P1, with unit-cell parameters a
      = 83.18, b = 86.61, c = 93.44 A. Assuming a reasonable range for V(M), the
      asymmetric unit could contain from three to five (alphaFe(III))(2) dimers. A peak
      present in the kappa = 180 degrees and kappa = 90 degrees sections is consistent
      with a fourfold axis and four dimers in the asymmetric unit. Comparison of the
      crystal structure of this enzyme with that of the 4-chlorocatechol 1,2
      dioxygenase recently crystallized from the same bacterium (Ferraroni et al.,
      2002) may reveal important details of the influence of the active-site
      conformation and the amino-acid substitutions involved in substrate selectivity.

PMID- 12499568
TI  - Crystallization and preliminary crystallographic analysis of the kinase
      recruitment domain of the PP2C-type phosphatase RsbU.
AB  - The general stress response of Bacillus subtilis provides a protective resistance
      to a variety of pressures. The key molecule is a subunit of RNA polymerase,
      sigma(B), which confers promoter specificity and is regulated by two signalling
      modules. Each module comprises protein kinases and phosphatases and 'switch'
      protein substrates for the kinase and phosphatase. The phosphorylation state of
      the switch molecules indirectly controls the activity of sigma(B). The binding of
      the kinase RsbT to the phosphatase RsbU stimulates its enzymatic activity towards
      its substrate, phosphorylated RsbV. To understand how these enzymes interact,
      thus regulating transcription, crystallization of the kinase-recruitment domain
      of RsbU in a form suitable for high-resolution structure determination is
      reported.

PMID- 12499569
TI  - Application of a two-liquid system to sitting-drop vapour-diffusion protein
      crystallization.
AB  - A new method of protein crystallization, the floating-drop vapour-diffusion
      technique, has been developed. The method combines the traditional sitting-drop
      vapour-diffusion technique and a novel two-liquid system. A crystallization drop
      composed of a mixture of sample and reagent floats on an insoluble and very dense
      liquid. Protein crystals are grown by vapour diffusion at the interface of the
      two liquids. The method makes it possible to remove the crystals easily without
      causing mechanical damage. This approach also significantly reduces the time and
      cost compared with the hanging-drop technique, which is presently the most
      popular method for protein crystallization.

PMID- 12499572
TI  - Development of a chymase inhibitor: pharmacological characterization of a chymase
      inhibitor in inflamed tissue remodeling and fibrosis.
AB  - Chymase, a chymotrypsin-like serine protease, has not only alternative
      angiotensin II-generating activity but also various activities involving
      inflammatory responses. However, little is known of its contribution to
      physiological functions. Therefore, chymase inhibitors are thought to be
      potentially useful as tools for elucidating the physiological functions of
      chymase and therapeutic agents. Within the last five years, many patents on non
      peptide chymase inhibitors have been published. We developed a potent non-peptide
      chymase inhibitor BCEAB (4-[1-[[bis-(4-methyl-phenyl)-methy]-carbamoyl]-3-(2
      ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid) and examined its effect on
      inflamed tissue remodeling and fibrosis using a hamster sponge implant model.
      BCEAB has high inhibitory activity against human chymase but not against
      angiotensin-converting enzyme, elastase and tryptase. In the hamster sponge
      implant model, oral administration of BCEAB for 15 days dose-dependently
      suppressed both the dry weight of granuloma tissues in the sponge discs and the
      amounts of hydroxyproline in the tissues gradually increased during the
      experimental period. These results suggest that chymase, at least in part,
      participates in the growth of granuloma tissues of inflammatory regions by
      stimulating fibroblast growth and extracellular matrix collagen deposition.
      Chymase inhibitors for oral administration, such as BCEAB, might be useful for
      clarifying the pathophysiological roles of chymase in vivo.

PMID- 12499573
TI  - Recombinant human chymase produced by silkworm-baculovirus expression system: its
      application for a chymase detection kit.
AB  - Human chymase is a mast cell-derived serine proteinase, which is a non
      angiotensin converting enzyme angiotensin II-generating enzyme. It appears to
      participate in various diseases, but it is unclear whether chymase plays major
      roles in physiological and pathophysiological functions in vivo. To obtain
      information on the physiological and pathophysiological functions of chymase and
      to search for diseases in which chymase participates, in the present study, we
      aimed at producing recombinant human chymase in large quantities and at
      developing an ELISA system using anti-human chymase antibodies. A recombinant
      human chymase was produced by a silkworm-baculovirus expression system. The
      recombinant chymase in active form was efficiently purified from larval hemolymph
      using cation-exchange and heparin column chromatography. This recombinant enzyme
      was enzymatically identical with native human chymase. On the other hand, the
      stability of the recombinant enzyme in cultured medium for mammalian cells at 37
      degrees C was very high as compared with the stability of the native enzyme; 20%
      of the activity was maintained 120 h after addition of medium. These results
      indicated that the recombinant enzyme could also utilize in vitro and in vivo
      assay systems. We obtained several anti-chymase monoclonal antibodies by using
      the recombinant human chymase as antigen. These antibodies were used to construct
      an ELISA system for measuring the chymase concentration in blood. As a result of
      preliminary examination using this ELISA system, it was shown that the chymase
      concentration in each serum from hypertensive patients is significantly higher
      than in normal serum. The ELISA system will be applicable for clinical diagnosis
      and in vivo evaluation systems for chymase-targeting drugs.

PMID- 12499574
TI  - Therapeutic potential of a specific chymase inhibitor in atopic dermatitis.
AB  - A novel therapeutic mechanism may be the key to improving the chief symptoms and
      signs of atopic dermatitis (AD), which are persistent pruritus and high serum
      IgE. We demonstrate here that mast cell chymase may be a possible initiating
      factor and that the orally active specific inhibitor Y-40613 may have a
      therapeutic potential in the treatment of AD. We found that Y-40613 (2-[5-amino-2
      (4-fluorophenyl)-1,6-dihydro-6-oxo-1-pyrimidinyl]-N-[1-[(5-methoxycarbonyl-2
      benzoxazolyl)carbonyl]-2-phenylethyl]acetamide) dose-dependently suppressed the
      scratching response in a mouse pruritus model, with inhibitory efficacy enhanced
      by combination with conventional drugs, suggesting that chymase contributes to
      the development of pruritus by a unique mechanism or mechanisms. In fact, chymase
      injected in the model induced the scratching response. In vitro IgE production
      from mouse B cells was increased by purified rat chymase and suppressed by Y
      40613. Increased serum IgE observed in Brown Norway rats injected with mercury
      chloride was suppressed by Y-40613. Furthermore, Y-40613 lowered ear thickness as
      well as serum IgE level in a mouse contact dermatitis model. Taken together,
      these findings suggest that the specific chymase inhibitor Y-40613 may ameliorate
      symptoms of AD through the dual inhibition of the chymase-dependent IgE
      production pathway and itching sensation.

PMID- 12499575
TI  - Development of the chymase inhibitor as an anti-tissue-remodeling drug:
      myocardial infarction and some other possibilities.
AB  - Chymase leading to tissue remodeling is expected to be a potent pharmaceutical
      target. Its functions in vivo are still unclear, because of lack of orally
      available inhibitors. Recently, however, the chymase inhibitor NK3201 (2-(5
      formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2
      pyridyloxy)]-2-heptyl] acetamide) was demonstrated to have oral activity against
      neointimal hyperplasia in dog models (Takai S. et al., Life Sci 69, 1725 - 1732
      (2001)). In this review, by showing the efficacy of NK3201 in some hamster
      models, chymase functions in vivo are summarized, and the potency of this chymase
      inhibitor is introduced. In vitro study, NK3201 showed potent chymase specific
      inhibitory activity, and Dixon plot analysis indicated competitive inhibition.
      Oral administration of NK3201 into normal rats resulted in rapid spread over
      every tissue except the brain, and sufficient activity to inhibit tissue chymase
      was detected even after 24 h. In passive cutaneous anaphylaxis, myocardial
      infarction and bleomycin-induced pulmonary fibrosis models, orally administered
      NK3201 showed potent inhibition of inflammatory response, tissue angiotensin II
      formation, and fibrosis, respectively. These data suggest that chymase has a
      vital role in tissue remodeling through promotion of the inflammatory response,
      tissue angiotensin II and tissue fibrosis. Our recent data indicated chymase
      participation in bladder fibrosis, like interstitial cystitis. Therefore, the
      orally active chymase inhibitor NK3201 may have protective effects on tissue
      remodeling in several diseases.

PMID- 12499576
TI  - Effect of chymase inhibitor on vascular proliferation.
AB  - In vascular tissues, angiotensin II is potentially cleaved from angiotensin I by
      chymase and angiotensin-converting enzyme (ACE). In the normal state, vascular
      ACE regulates local angiotensin II formation and plays a crucial role in the
      regulation of blood pressure, whereas chymase is stored in mast cells and has no
      enzymatic activity. Chymase is activated immediately upon its release into the
      extracellular matrix in vascular tissues after mast cells have been activated by
      stimuli such as vessel injury by grafting or a balloon catheter. In dog grafted
      veins, chymase activity is increased, and the vascular proliferation is
      suppressed by either a chymase inhibitor or an angiotensin II receptor blocker.
      After balloon injury in dog vessels, chymase activity is significantly increased
      in the injured artery, and a chymase inhibitor is effective in preventing the
      vascular proliferation, but an ACE inhibitor is ineffective. Chymase plays an
      important role in the development of vascular proliferation via the induction of
      local angiotensin II formation in injured vessels.

PMID- 12499577
TI  - KB-R7943, a Na+/Ca2+ exchange inhibitor, does not suppress ischemia/reperfusion
      arrhythmias nor digitalis arrhythmias in dogs.
AB  - KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate)
      has been used as a pharmacological tool to block the Ca(2+) influx-mode of the
      Na(+)/Ca(2+) exchanger, which is thought to contribute to ischemia/reperfusion
      and digitalis arrhythmias. We examined effects of KB-R7943 on
      ischemia/reperfusion arrhythmias in beagle dogs anesthetized with sodium
      pentobarbital. Lead II ECG and BP were measured. KB-R7943 or the solvent (10%
      DMSO) was injected i.v. as a bolus, and 5 min later, the left anterior descending
      coronary artery was occluded for 30 min followed by reperfusion. KB-R7943 at 5 or
      10 mg/kg increased BP without changing ECG parameters including the heart rate.
      Although 5 mg/kg KB-R7943 deceased the number of arrhythmic beats during the
      ischemic period, mortality due to ischemia/reperfusion was not decreased by KB
      R7943 (5 and 10 mg/kg). KB-R7943 at 5 mg/kg also did not suppress the ouabain
      induced arrhythmias. These negative results suggest that Na(+)/Ca(2+) exchange
      inhibition may not be a useful strategy of suppressing arrhythmias.

PMID- 12499578
TI  - Effects of methylprednisolone on bone formation and resorption in rats.
AB  - Excessive glucocorticoids induce osteoporosis. However, there is some controversy
      regarding the mechanism of action, and even the endpoint result. The present
      study was carried out to obtain further insight into the action of
      glucocorticoids on bone formation and resorption in rats. Growing rats were
      injected subcutaneously with methylprednisolone (mPSL) at doses of 0, 2.5, 5, 10
      or 20 mg/kg per day for 4 weeks. Bone mineral density (BMD), enchondral and
      periosteal bone formation, collagen synthetic activities of osteoblasts, numbers
      of osteoblasts and osteoclasts, and serum markers to assess bone turnover were
      determined. Administration of mPSL dose-dependently increased the BMD in the
      tibial metaphysis, while it dose-dependently decreased the BMD in the diaphysis.
      Both enchondral and periosteal bone formation were decreased in a dose-dependent
      fashion. The incorporation and secretion of (3)H-proline by osteoblasts were both
      decreased in trabecular and cortical bones. The number of osteoclasts, together
      with the number of osteoblasts, in the tibial metaphysis was drastically
      decreased. Serum alkaline phosphatase and osteocalcin were decreased at higher
      doses. These results support the recent notion that glucocorticoids inhibit both
      bone formation and resorption. In addition, BMD as an endpoint result might
      differ from site to site in bone due to a different balance between bone
      formation and resorption.

PMID- 12499579
TI  - Effects of fragrance inhalation on sympathetic activity in normal adults.
AB  - We investigated the effects of fragrance inhalation on sympathetic activity in
      normal adult subjects using both power spectral analysis of blood pressure
      fluctuations and measurement of plasma catecholamine levels. Fragrance inhalation
      of essential oils, such as pepper oil, estragon oil, fennel oil or grapefruit
      oil, resulted in 1.5- to 2.5-fold increase in relative sympathetic activity,
      representing low frequency amplitude of systolic blood pressure (SBP-LF
      amplitude), compared with inhalation of an odorless solvent, triethyl citrate
      (P<0.05, each). In contrast, fragrance inhalation of rose oil or patchouli oil
      caused a 40% decrease in relative sympathetic activity (P<0.01, each). Fragrance
      inhalation of pepper oil induced a 1.7-fold increase in plasma adrenaline
      concentration compared with the resting state (P = 0.06), while fragrance
      inhalation of rose oil caused a 30% decrease in adrenaline concentration
      (P<0.01). Our results indicate that fragrance inhalation of essential oils may
      modulate sympathetic activity in normal adults.

PMID- 12499580
TI  - Axonal and dendritic extension by protopanaxadiol-type saponins from ginseng
      drugs in SK-N-SH cells.
AB  - Extension of axons and dendrites in neurons may compensate for and repair damaged
      neuronal networks in the dementia brain. To find out drugs capable of
      regenerating the neuronal network, we focused on several herbal drugs belonging
      to the genus Panax, kinds of Ginseng, and investigated neurite outgrowth activity
      of their extracts and compounds. We found that the methanol extracts of Ginseng
      (root of P. ginseng), Notoginseng (root of P. notoginseng) and Ye-Sanchi in
      Chinese (rhizome of a relative to P. vietnamensis) increased neurite outgrowth in
      SK-N-SH cells. The protopanaxadiol-type saponins, ginsenosides Rb(1) and Rb(3),
      and notoginsenosides R(4) and Fa isolated from Ye-Sanchi extract extended
      neurites, while protopanaxatriol-, ocotillol- and oleanane-type saponins had no
      effect on the neurite outgrowth. The percentage of cells with multipolar neurites
      and number of varicosities were intensely high in cells treated with the methanol
      extract of Ye-Sanchi as well as ginsenosides Rb(1) and Rb(3), and
      notoginsenosides R(4) and Fa. Both phosphorylated NF-H-expressing neurites and
      MAP2-expressing ones were extended by treatment with those saponins and the
      extract. Especially, longer neurites were mainly positive for phosphorylated NF
      H. These results suggest that protopanaxadiol-type saponins enhance axonal and
      dendritic formation activity.

PMID- 12499581
TI  - Daily expression of mRNAs for the mammalian Clock genes Per2 and clock in mouse
      suprachiasmatic nuclei and liver and human peripheral blood mononuclear cells.
AB  - The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) of
      the hypothalamus and in most peripheral tissues. Clock genes drive the biological
      clock. However, circadian expression variations of the human clock genes are
      still unclear. In this study, we analyzed the daily variations of mPer2 and
      mClock mRNA expression in both the mouse SCN and liver to evaluate the central
      and peripheral alterations in the rodent clock genes. We also examined whether
      there are the daily variations of the clock genes hPer2 and hClock in human
      peripheral blood mononuclear cells (PBMCs). The daily variation of mClock and
      mPer2 mRNA expression in mouse SCN and liver were determined at ZT2, ZT6, ZT10,
      ZT14, ZT18 or ZT22. We isolated PBMCs from 9 healthy volunteers at 9:00 and 21:00
      and examined the expression of hPer2 and hClock mRNA by RT-PCR analysis. The
      animals exhibited a robust daily rhythm in the RNA levels of mPer2 in the SCN and
      liver (P<0.01, respectively). In humans, hPer2 mRNA expression also had daily
      variation, and the hPer2 mRNA levels at 9:00 were significantly larger than those
      at 21:00 (P<0.01). While, the Clock mRNA in both mice and humans exhibited no
      daily variation. These findings suggest that the variation in hPer2 mRNA
      expression may be useful for assessing human peripheral circadian systems.

PMID- 12499582
TI  - Naloxone-precipitated morphine withdrawal elicits increases in c-fos mRNA
      expression in restricted regions of the infant rat brain.
AB  - This paper is the first report of a genetic index for morphine withdrawal in
      infant rats. We examined the effects of naloxone (2 mg/kg) on c-fos mRNA levels
      in brains of infant and adult rats following repeated treatment with morphine (20
      mg/kg, once daily for 5 days). One hour after a single administration of naloxone
      (naloxone challenge), an increase in c-fos mRNA was observed in the olfactory
      bulb, hypothalamus and medulla oblongata of infant rats, and in the olfactory
      bulb and hypothalamus, but not in the medulla oblongata of adult rats. The c-fos
      mRNA levels returned to control levels 6 h after the naloxone challenge. The
      increase in c-fos mRNA levels was followed by body weight loss in both infant and
      adult rats. When MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonist, was co-administered along with morphine, it inhibited the naloxone
      induced increases in c-fos mRNA levels in infant rats following repeated morphine
      administration. These results suggest that physical dependence develops in infant
      rats following repeated morphine administration and that the increment of c-fos
      mRNA levels is a useful indicator for naloxone-precipitated morphine withdrawal
      in infant as well as in adult rats.

PMID- 12499583
TI  - Inhibitory effect of the water-soluble extract of Salvia miltiorrhiza on
      neutrophil-endothelial adhesion.
AB  - The effect of the water-soluble extract (WSE) of Salvia miltiorrhiza on
      neutrophil-endothelial cell adhesion was investigated. Cell adhesion was
      evaluated by testing neutrophil myeloperoxidase activity: expression of adhesion
      molecules in human umbilical vein endothelial cells (HUVEC) was measured by
      ELISA: the neutrophil activation rate induced by N-formyl-methionyl-leucyl
      phenylalanine (fMLP) was tested by the method of nitroblue tetrazolium (NBT)
      reduction. The results showed that the adhesion rate of neutrophils to
      unstimulated HUVEC was very low. TNFalpha (50 - 800 U/ml) increased the adhesion
      of neutrophils to TNFalpha-stimulated HUVEC in a concentration- and time
      dependent manner. The WSE of Salvia miltiorrhiza (0.01 - 1 mg/ml) dose
      dependently inhibited the adhesion of neutrophils. The inhibitory rate of the WSE
      of Salvia miltiorrhiza at 0.01, 0.1 and 1 mg/ml was 6.2%, 17.0% and 28.0%,
      respectively. fMLP (10(-9) - 10(-5) M) increased the activation rate of
      neutrophils concentration-dependently. The WSE of Salvia miltiorrhiza also
      concentration-dependently inhibited the adhesion of fMLP-activated neutrophils to
      HUVEC. The inhibitory rate of the WSE of Salvia miltiorrhiza at 0.001, 0.01 and
      0.1 mg/ml was 5.3%, 26.3% and 28.9%, respectively. Moreover, TNFalpha upregulated
      expression of adhesion molecule E-selectin, ICAM-1 and VCAM-1. The WSE of Salvia
      miltiorrhiza had an inhibitory effect on TNF alpha-induced expression of these
      molecules. These results indicated that the WSE of Salvia miltiorrhiza inhibited
      neutrophil-endothelial adhesion. The action mechanism of the WSE of Salvia
      miltiorrhiza was partly related to suppressing the expression of adhesion
      molecules.

PMID- 12499584
TI  - Method for simultaneous recording of the prostatic contractile and urethral
      pressure responses in anesthetized rats and the effects of tamsulosin.
AB  - We simultaneously recorded the prostatic contractile and urethral pressure
      responses to electrical stimulation (ES) of the hypogastric nerves (HGNs) or
      phenylephrine in anesthetized rats and studied the effects of tamsulosin on these
      responses. At 0.01 and 0.1 mg/kg, i.v., tamsulosin inhibited the prostatic
      responses to ES of the HGNs in a dose-dependent manner, while at 1 microg/kg,
      i.v., it reduced the response to phenylephrine (0.01 mg/kg, i.v.) to about 26% of
      the nonantagonized level. These inhibitory effects on prostatic responses were
      maintained for 60 min. Tamsulosin exerted an inhibitory effect on the urethral
      response to ES of the HGNs at 0.01 mg/kg, i.v. but not at 0.1 mg/kg, i.v. At 1
      microg/kg, i.v., tamsulosin also reduced the urethral response to phenylephrine
      to about 46% of the nonantagonized level; this effect was maintained for 60 min.
      Furthermore, tamsulosin was found to exert a stronger inhibitory effect on the
      prostatic response than on the urethral response induced by sympathetic nerve
      activation. Our findings suggest that rat urethral sympathetic nerve terminals
      may contain prejunctional alpha1 adrenoceptors that modulate the release of
      norepinephrine.

PMID- 12499585
TI  - Enhanced lipid peroxidation in epileptics with null genotype of glutathione S
      transferase M1 and intractable seizure.
AB  - Null genotype of glutathione S-transferase class me (GSTM1(-)) and the plasma
      level of malondialdehyde (MDA) were determined in normal subjects, epileptics
      with good seizure control and epileptics with intractable seizure. The frequency
      of GSTM1(-) of the epileptics with intractable seizure was significantly higher
      than that of the group with good seizure control and that of the normal subjects.
      The average plasma level of MDA of the patients with GSTM1(-) genotype was higher
      than that of the subjects with GSTM1(+) in either the normal or epileptic group.
      Thus, the GSTM1(-) genotype may be one of the genetic factors involved in the
      response to anticonvulsant therapy.

PMID- 12499586
TI  - Cross-coupling reactions of organosilicon compounds: new concepts and recent
      advances.
AB  - This review highlights the rapid evolution of the newly-developed class of
      palladium-catalyzed cross-coupling reactions of organosilicon compounds. A myriad
      of heteroatom-containing silicon moieties (silyl hydrides, siletanes, silanols,
      silyl ethers, orthosiliconates, di- and polysiloxanes and pyridylsilanes) undergo
      mild and stereospecific cross-coupling. The diversity of methods for introduction
      of silicon groups into organic molecules and the range of organic electrophiles
      that can be used are emphasized.

PMID- 12499587
TI  - Preparation of antipyretic analgesic by direct compression and its evaluation.
AB  - Direct compression is able to produce tablets at a lower cost than wet
      granulation and tableting method, due to a fewer items of process validation. In
      this study, acetaminophen was used as a medicine with various granular diameters
      to formulate tablets by direct compression, thus evaluating their physical
      properties. Consequently, direct compression was found effective in formulating
      tablets with excellent physical properties, with the granular diameter taken into
      account. It was confirmed that tablets produced by direct compression were
      similar in physical properties in tablets produced by wet granulation and
      tableting method. Further, it was suggested that use of a dry-type binder would
      make it possible to provide a tablet having higher content of the medicine with
      excellent physical properties.

PMID- 12499588
TI  - Optimization of operating conditions in a high-shear mixer using dem model:
      determination of optimal fill level.
AB  - For the purpose of evaluating optimal fill level of starting materials in a high
      shear mixer, discrete element method (DEM) simulation was conducted to visualize
      kinetic status between particles. The simulation results obtained by changing
      fill levels were used to determine solid fraction of particles, particle
      velocity, particle velocity vector, and kinetic energy and discuss the flow
      pattern. Optimal fill level was obtained from the information on these matters.
      It was pointed out that understanding the kinetic energy between particles in an
      agitating vessel was effective in determining the optimal fill level. Granulation
      experiment was conducted to validate the optimal fill level obtained by the
      simulation, confirming the good agreement between these two results. It was
      pointed out that determination of kinetic energy between particles through the
      simulation was effective in obtaining an index of the kinetic status of
      particles. Further, it was confirmed that the simulation could provide more
      information than conventional granulation experiments could provide and also
      helpful in optimizing the operating conditions.

PMID- 12499589
TI  - Novel sphingolipids from Conyza canadensis.
AB  - New sphingolipids, 1,3,5-trihydroxy-2-hexadecanoylamino-(6E,9E)-heptacosdiene
      (1). 1,3,5-trihydroxy-2-hexadecanoylamino-(6E,9E)-heptacosdiene-1-O
      glucopyranoside (2). 1,3-dihydroxy-2-hexanoylamino-(4E)-heptadecene (3). have
      been isolated from Conyza canadensis, along with five known compounds, p
      hydroxybenzoic acid, 3,5-dihydroxybenzoic acid, 3,5-dimethoxybenzoic acid, 3beta
      hydroxyolean-12-en-28-oic acid, and 3beta-erythrodiol, isolated for the first
      time from this species. Their structures were determined by spectroscopic methods
      ((1)H- and (13)C-NMR, IR and MS) and two dimensional (2D)-NMR experiments.

PMID- 12499590
TI  - Taxumairols X--Z, new taxoids from Taiwanese Taxus mairei.
AB  - In addition to 19-dydroxybaccatin III, 1beta-hydroxy-5 alpha-deacetylbaccatin I,
      taxayuntin G and 13-O-deacetyltaxumairol Z (4), three new taxane diterpenoids,
      taxumairols X (1), Y (2), Z (3) have been isolated from extracts of the Formosan
      Taxus mairei (LEMEE & LEVL.) S. Y. HU. Compounds 1-2 belong to the 11(15-->1)
      abeo-taxane system, having a tetrahydrofuran ring at C-2, C-3, C-4 and C-20. The
      new compound 3 and 4, which was misidentified previously are derivatives of 11(15
      ->1)-abeo-taxane with an intact oxirane system. The structures of compounds 1-4
      were elucidated on the basis of extensive two dimensional (2D)-NMR analysis.

PMID- 12499591
TI  - Anti-allergic agents from natural sources (4): anti-allergic activity of new
      phloroglucinol derivatives from Mallotus philippensis (Euphorbiaceae).
AB  - Two new phloroglucinol derivatives, mallotophilippen A (1). and B (2). were
      isolated from the fruits of Mallotus philippensis. These compounds were
      identified, using chemical and spectral data, as 1-[5,7-dihydroxy-2,2-dimethyl-6
      (2,4,6-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-yl]-2-methyl-butan-1
      one and 1-[6-(3-Acetyl-2,4,6-trihydroxy-5-methyl-benzyl)-5,7-dihydroxy-2,2
      dimethyl-2H-chromen-8-yl]-2-methyl-butan-1-one, respectively. They inhibited
      nitric oxide (NO) production and inducible NO synthase (iNOS) gene expression by
      a murine macrophage-like cell line (RAW 264.7), which was activated by
      lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma).
      Furthermore, they inhibited histamine release from rat peritoneal mast cells
      induced by Compound 48/80. These results suggest that the novel phloroglucinol
      derivatives have anti-inflammatory effects.

PMID- 12499592
TI  - Physicochemical analyses of phase transition and dehydration processes of a new
      oral 1beta-methylcarbapenem antibiotic agent, CS-834.
AB  - The characterizations of the anhydrate (A-form), monohydrate (B1-form), and
      dihydrate (B2-form) of CS-834 were investigated by powder X-ray diffraction,
      differential scanning calorimetry (DSC), thermogravimetry-differential thermal
      analysis (TG-DTA), infrared spectroscopy, and Karl Fischer moisture titration.
      The typical DSC curve of the B2-form showed five endothermic peaks at 35.0, 46.4,
      56.2, 99.2, and 190.4 degrees C and an exothermic peak at 123.4 degrees C. In TG
      DTA analysis, the three peaks at 35.0, 46.4, and 56.2 degrees C had a total
      weight loss of 7.3%, corresponding to the release of two water molecules. From
      morphological observation under thermomicroscopy, the endothermic peak at 99.2
      degrees C was attributed to the melting of the dehydrous crystals (B0-form) and
      the exothermic peak at 123.4 degrees C to the recrystallization to the A-form
      crystals. The endothermic peak at 190.4 degrees C was due to the melting of the A
      form crystals. After incubation for 6.0 h at 35, 50, 60, and 80 degrees C, the
      powder X-ray diffraction patterns of the B2-form indicated that it was converted
      into the A-form via the B1-form and B0-form. Thus CS-834 exists in homologous
      hydrous crystal forms in multiple-phase transformations with the dehydration of
      two water molecules.

PMID- 12499593
TI  - Pyridazines. Part 31: synthesis and antiplatelet activity of 4,5-disubstituted-6
      phenyl-3(2H)-pyridazinones.
AB  - This paper describes the synthesis and the antiplatelet activity of a series of
      4,5-disubstituted-6-phenyl-3(2H)-pyridazinones. Some of these compounds show a
      dose-dependent activity and were found to be more active than their 5-substituted
      analogues.

PMID- 12499594
TI  - Hydrophobicity parameters determined by reversed-phase liquid chromatography. XV:
      optimal conditions for prediction of log P(oct) by using RP-HPLC procedures.
AB  - The use of log k derived from reversed phase (RP)-HPLC retention times provides a
      convenient method for estimating log P(oct) values (P(oct): 1-octanol/water
      partition coefficient). In order to establish optimal HPLC conditions, the
      difference between chromatographic (C18 modified column and aqueous methanol
      eluents) and bulk solvent systems was examined by use of a batch-like
      equilibration with octane/aqueous methanol. Comparison of values for log P(O/M-W)
      (log P for the Octane/MeOH-Water partitioning system) and log k measured for
      monosubstituted pyrazines at different methanol concentrations, showed closest
      correlation (r, 0.94) with 50% aqueous methanol; and importantly, under these
      conditions, log k shows even better correlation (r, 0.99) with log P(oct).
      Effects of residual silanols on HPLC retention with C18 stationary phases were
      examined. The results show that, in the presence of a small quantity of
      accessible silanols, the use of 50% aqueous methanol (M50) as eluent yields
      values of log k directly proportional to log P(oct) in accord with our earlier
      proposal that use of log k(M50) provides a convenient means for rapid estimation
      and prediction of log P(oct).

PMID- 12499595
TI  - Reaction of phosgene with the tricycle related to the minor base of phenylalanine
      transfer ribonucleic acids.
AB  - 1-Benzylwye (8) underwent electrophilic substitution at the 7-position in the
      presence of phosgene and pyridine in tetrahydrofuran (THF) to afford the 1,4
      dihydropyridines (11, 10, and 14) together with the carboxylic acid 6 and its
      methyl ester 2 after short treatment of the reaction mixture with methanol and
      then with water. When triethylamine was used instead of pyridine, phosgene
      reacted with triethylamine rather than 8, producing (E)-3-(diethylamino)propenoyl
      chloride (17) and diethylcarbamoyl chloride (18).

PMID- 12499596
TI  - The effect of various substances on the suppression of the bitterness of quinine
      human gustatory sensation, binding, and taste sensor studies.
AB  - The purpose of this study was to quantify the degree of suppression of the
      perceived bitterness of quinine by various substances and to examine the
      mechanism of bitterness suppression. The following compounds were tested for
      their ability to suppress bitterness: sucrose, a natural sweetener; aspartame, a
      noncaloric sweetener; sodium chloride (NaCl) as the electrolyte; phosphatidic
      acid, a commercial bitterness suppression agent; and tannic acid, a component of
      green tea. These substances were examined in a gustatory sensation test in human
      volunteers, a binding study, and using an artificial taste sensor. Sucrose,
      aspartame, and NaCl were effective in suppressing bitterness, although at
      comparatively high concentrations. An almost 80% inhibition of bitterness
      (calculated as concentration %) of a 0.1 mM quinine hydrochloride solution
      required 800 mM of sucrose, 8 mM of aspartame, and 300 mM NaCl. Similar levels of
      bitterness inhibition by phosphatidic acid and tannic acid (81.7, 61.0%,
      respectively) were obtained at much lower concentrations (1.0 (w/v)% for
      phosphatidic acid and 0.05 (w/v)% for tannic acid). The mechanism of the
      bitterness-depressing effect of phosphatidic acid and tannic acid was
      investigated in terms of adsorption and masking at the receptor site. With
      phosphatidic acid, 36.1% of the bitterness-depressing effect was found to be due
      to adsorption, while 45.6% was due to suppression at the receptor site. In the
      case of 0.05 (w/v)% tannic acid, the total bitterness-masking effect was 61.0%.
      The contribution of the adsorption effect was about 27.5% while the residual
      masking effect at the receptor site was almost 33%. Further addition of tannic
      acid (0.15 (w/v)%), however, increased the bitterness score of quinine, which
      probably represents an effect of the astringency of tannic acid itself. Finally,
      an artificial taste sensor was used to evaluate or predict the bitterness
      depressing effect. The sensor output profile was shown to reflect the depressant
      effect at the receptor site rather well. Therefore, the taste sensor is
      potentially useful for predicting the effectiveness of bitterness-depressant
      substances.

PMID- 12499597
TI  - Inhibitory effects of 1,3-selenazol-4-one derivatives on mushroom tyrosinase.
AB  - This study reports depigmenting potency of 1,3-selenazol-4-one derivatives, which
      would be based upon the finding of direct inhibition to mushroom tyrosinase. 1,3
      Selenazol-4-one derivatives exhibited inhibitory effect on dopa oxidase activity
      of mushroom tyrosinase. In this study, inhibitory effects of six kinds of 1,3
      selenazol-4-one derivatives (A, B, C, D, E and F) on mushroom tyrosinase were
      investigated. Compounds at a concentration of 500 microM exhibited 33.4-62.1% of
      inhibition on dopa oxidase activity of mushroom tyrosinase. Their inhibitory
      effects were higher than that of kojic acid (31.7%), a well known tyrosinase
      inhibitor. 2-(4-Methylphenyl)-1,3-selenazol-4-one (A) exhibited the strongest
      inhibitory effect among them dose-dependently and in competitive inhibition
      manner.

PMID- 12499598
TI  - Effect of the hydrophobic nature of triacetyl-beta-cyclodextrin on the
      complexation with nicardipine hydrochloride: physicochemical and dissolution
      properties of the kneaded and spray-dried complexes.
AB  - The inclusion ability of triacetyl-beta-cyclodextrin (TAbetaCD), a hydrophobic
      cyclodextrin (CD) derivative was examined, using nicardipine hydrochloride (NC)
      as model drug. The binary compounds were prepared in a 1 : 1 molar ratio by the
      kneading and the spray-drying techniques. In order to confirm the complexation
      between NC and TAbetaCD in the solid state, differential scanning calorimetry, X
      ray diffractometry, Fourier transformation-infrared spectroscopy and scanning
      electron microscopy were carried out and the results were compared with the
      corresponding physical mixture in the same molar ratio. The kneaded product
      presented only slight modifications on the drug physicochemical and morphological
      properties, which could mean that no complex formation occurred during this
      process. In contrast, spray-drying was found to produce inclusion complexes with
      amorphous nature. In vitro dissolution studies were carried out in simulated
      gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the United States
      Pharmacopoeia (USP) basket method. The NC in vitro release from the kneaded and
      spray-dried products was markedly retarded in both dissolution media. However,
      this retarding effect was significantly more evident for the spray-dried
      compound. It was concluded that the formation of real inclusion complexes could
      only be achieved by the spray-drying method.

PMID- 12499599
TI  - New triterpenoids from Tricholoma saponaceum.
AB  - Six new triterpenes, saponaceolides E (1), F (2), and G (3), and saponaceoic
      acids I (4), II (5), and III (6) were isolated from the fruiting body of the
      fungus Tricholoma saponaceum, and their structures were elucidated on the base of
      extensive NMR experiments. Compounds 1 and 2 exhibited inhibitor activity against
      B16 and L929 cells.

PMID- 12499600
TI  - A novel cytotoxic C-methylated biflavone, taiwanhomoflavone-B from the twigs of
      Cephalotaxus wilsoniana.
AB  - A novel C-methylated biflavone, taiwanhomoflavone-B (1), together with known
      compounds, 7,4',7"-tri-O-methylamentoflavone, 6-C-methylnaringenin and apigenin-7
      O-beta-glucoside were isolated from an ethanolic extract of Cephalotaxus
      wilsoniana. The structure of 1 was elucidated on the basis of spectroscopic
      analysis. Taiwanhomoflavone-B is cytotoxic with ED(50) values of 3.8 and 3.5
      microg/ml, against KB oral epidermoid carcinoma and Hepa-3B hepatoma cells,
      respectively.

PMID- 12499601
TI  - New quinone sulfates from the crinoids Tropiometra afra macrodiscus and
      Oxycomanthus japonicus.
AB  - Quinone pigments in the crinoids were investigated. New quinone sulfates 1 and 3
      were isolated from Tropiometra afra macrodiscus and Oxycomanthus japonicus,
      respectively. The structures 1 and 3 were determined to be 1,6,8-trihydroxy-3
      propylanthraquinone-2-carboxylic acid 6-O-sulfate (ptilometric acid 6-O-sulfate)
      and 2-butanoyl-3,6,8-trihydroxy-1,4-naphtoquinone 6-O-sulfate, respectively, by
      chemical and spectroscopic analysis. Ptilometric acid 6-O-sulfate (1) showed an
      antifeedant activity on fish.

PMID- 12499602
TI  - Chromone and phenanthrene alkaloids from Dennettia tripetala.
AB  - Dennettine, a new 2,6-dimethoxychromone and three known phenanthrene alkaloids
      (uvariopsine, stephenanthrine and argentinine) in addition to the phenolic and
      known compound vanillin were isolated from the roots of Dennettia tripetala.
      Their structures were determined by physical and spectroscopical one dimensional
      (1D) and 2D-NMR analysis, including heteronuclear multiple bond correlation and
      nuclear Overhauser enhancement spectroscopy.

PMID- 12499603
TI  - New phenylethanoid glycosides from Bacopa monniera.
AB  - Three new phenylethanoid glycosides, viz. monnierasides I-III (1-3) along with
      the known analogue plantainoside B were isolated from the glycosidic fraction of
      Bacopa monniera. Their structures were elucidated mainly on the basis of two
      dimensional (2D) NMR spectral analyses.

PMID- 12499604
TI  - A new acylated flavonol glycoside from the leaves of Eriobotrya japonica.
AB  - A new acylated flavonol glycoside was isolated from the leaves of Eriobotrya
      japonica along with two known flavonol glycosides. Their structures were
      determined by extensive spectroscopic investigation.

PMID- 12499605
TI  - Investigation of water mobility and diffusivity in hydrating micronized low
      substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and
      hydroxypropyl cellulose matrix tablets by magnetic resonance imaging (MRI).
AB  - The water mobility and diffusivity in the gel-layer of hydrating low-substituted
      hydroxypropyl cellulose (LH41) tablets with or without a drug were investigated
      by magnetic resonance imaging (MRI) and compared with those properties in the gel
      layer of hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC)
      tablets. For this purpose, a localized image-analysis method was newly developed,
      and the spin-spin relaxation time (T(2)) and apparent self-diffusion coefficient
      (ADC) of water in the gel-layer were visualized in one-dimensional maps. Those
      maps showed that the extent of gel-layer growth in the tablets was in the order
      of HPC>HPMC>>LH41, and there was a water mobility gradient across the gel-layers
      of all three tablet formulations. The T(2) and ADC in the outer parts of the gel
      layers were close to those of free water. In contrast, these values in the inner
      parts of the gel-layer decreased progressively; suggesting that the water
      mobility and diffusivity around the core interface were highly restricted.
      Furthermore, the correlation between the T(2) of (1)H proton in the gel-layer of
      the tablets and the drug release rate from the tablets was observed.

PMID- 12499606
TI  - A new synthesis of a potent cancer chemopreventive agent, 13-oxo-15,16-dinorlabda
      8(17),11E-dien-19-oic acid from trans-communic acid.
AB  - The first synthesis of a labdane diterpenoid, (-)-13-oxo-15,16-dinorlabda
      8(17),11E-dien-19-oic acid [(-)-1a], isolated from the stem bark of Thuja
      standishii (GORD.) CARR., from the major component trans-communic acid (3a) is
      described.

PMID- 12499607
TI  - Isolation and characterization of dinochrome A and B, anti-carcinogenic active
      carotenoids from the fresh Water red tide Peridinium bipes.
AB  - Two epimeric carotenoids, named dinochromes A (2) and B (3), were isolated from
      the fresh water red tide Peridinium bipes, as anti-carcinogenic compounds. The
      stereostructure of dinochrome A and B were characterized to be
      (3S,5R,6R,3'S,5'R,8'R)- and (3S,5R,6R,3'S,5'R,8'S)-5',8'-epoxy-6,7-didehydro
      5,6,5',8'-tetrahydro-beta,beta-carotene-3,5,3'-triol 3-O-acetate, respectively by
      (1)H- and (13)C-NMR, and circular dichroism (CD) data. Dinochromes A (2) and B
      (3) inhibit 12-O-tetradecanoyl phorbol 13-acetate (TPA)-stimulated (32)P
      incorporation into the phosholipids of HeLa cells. Furthermore, dinochrome A was
      found to inhibit the proliferation of human malignant tumor cells, such as GOTO,
      OST and HeLa cells.

PMID- 12499608
TI  - Chemical modification of coumarin dimer and HIV-1 integrase inhibitory activity.
AB  - A systematic series of chemically modified coumarin dimmers has been synthesized
      and tested for their inhibitory activity against HIV-1 integrase. We observed
      that modified coumarin dimmers containing hydrophobic moiety on the linker
      display potent inhibitory activities.

PMID- 12499609
TI  - Photoreaction generating active oxygens of In(3+)-tetrakis(4-methylpyridyl)
      porphine in the presence of albumins.
AB  - The complex formation of In(3+)-tetrakis(4-N-methylpyridyl)-porphine (In-TMPyP)
      with albumin was studied by resonance Raman spectroscopy. Albumin coordinated to
      In(3+) through the -S(-) group(s). The photoreaction was investigated using the
      visible spectral change and In-TMPyP-thiourea complex was used as a model. It was
      demonstrated that the complex in a weak basic solution (pH 8.5) is excited by
      light and the excited complex converts oxygen to superoxide anion, which finally
      cleavages the porphine ring of In-TMPyP.

PMID- 12499610
TI  - Recent progress in gene therapy for cardiovascular disease.
AB  - Gene therapy is emerging as a potential strategy for the treatment of
      cardiovascular diseases, such as peripheral arterial disease, ischemic heart
      disease, restenosis after angioplasty, vascular bypass graft occlusion and
      transplant coronary vasculopathy, for which no known effective therapy exists.
      The first human trial in cardiovascular disease started in 1994 treating
      peripheral vascular disease with vascular endothelial growth factor (VEGF) and
      since then, many different potent angiogenic growth factors have been tested in
      clinical trials for the treatment of peripheral arterial disease. In addition,
      therapeutic angiogenesis using the VEGF gene has been used to treat ischemic
      heart disease since 1997. The results from these clinical trials have exceeded
      expectations; improvement in the clinical symptoms of peripheral arterial disease
      and ischemic heart disease has been reported. Another strategy for combating the
      disease processes, targeting the transcriptional process, has been tested in a
      human trial. IN particular, transfection of cis-element double-stranded (ds)
      oligodeoxynucleotides (ODN) (= decoy) is a powerful tool in a new class of anti
      gene strategies. Transfection of ds-ODN corresponding to the cis sequence will
      attenuate the authentic cis-trans interaction, leading to removal of trans
      factors from the endogenous cis-elements and subsequent modulation of gene
      expression. Genetically modified vein grafts transfected with a decoy against
      E2F, an essential transcription factor in cell cycle progression, appear to have
      long-term potency in human patients. There is great potential in gene therapy for
      cardiovascular disease.

PMID- 12499611
TI  - Large scale cohort study of the relationship between serum cholesterol
      concentration and coronary events with low-dose simvastatin therapy in Japanese
      patients with hypercholesterolemia.
AB  - Hyperlipidemia is a well-established risk factor for primary coronary heart
      disease (CHD). Although simvastatin is known to lower serum lipid concentrations,
      the protective effect of such lipid-lowering therapy against primary CHD has not
      been established in Japanese patients with hypercholesterolemia. The Japan Lipid
      Intervention Trial was a 6-year, nationwide cohort study of 47,294 patients
      treated with open-labeled simvastatin (5-10 mg/day) and monitored by physicians
      under standard clinical conditions. The aim of the study was to determine the
      relationship between the occurrence of CHD and the serum lipid concentrations
      during low-dose simvastatin treatment. Simvastatin reduced serum concentrations
      of total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C) and
      triglyceride (TG), by 18.4%, 26.8% and 16.1% on average, respectively, during the
      treatment period. The risk of coronary events was higher when the average TC
      concentration was > or =240 mg/dl and the average LDL-C concentration was > or
      =160 mg/dl. The incidence of coronary events increased in the patients with TG
      concentration > or =300 mg/dl compared with patients with TG concentration <150
      mg/dl. The high-density lipoprotein cholesterol (HDL-C) inversely correlated with
      the risk of coronary events. The J-curve association was observed between average
      TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent
      cause of death. The health of patients should be monitored closely when there is
      a remarkable decrease in TC and LDL-C concentrations with low-dose statin. A
      reasonable strategy to prevent coronary events in Japanese hypercholesterolemic
      patients without prior CHD under low-dose statin treatment might be regulating
      the serum lipid concentrations to at least <240 mg/dl for TC, <160 mg/dl for LDL
      C, <300 mg/dl for TG, and >40 mg/dl for HDL-C.

PMID- 12499612
TI  - Large scale cohort study of the relationship between serum cholesterol
      concentration and coronary events with low-dose simvastatin therapy in Japanese
      patients with hypercholesterolemia and coronary heart disease: secondary
      prevention cohort study of the Japan Lipid Intervention Trial (J-LIT).
AB  - Hyperlipidemia is primarily implicated in the progression of coronary heart
      disease (CHD) and its treatment is essential for patients with a history of CHD.
      Statins such as simvastatin, the lipid-lowering agents, are well-known for their
      ability to normalize patient's serum lipid levels. The Japan Lipid Intervention
      Trial study of simvastatin is the first nationwide investigation of the
      relationship between serum lipid levels and the development of CHD in Japanese
      patients with hypercholesterolemia. Of 5,127 patients, exclusively with a history
      of documented CHD at enrollment, 4,673 were treated with open-labeled simvastatin
      at an initial dose of 5-10 mg/day and were monitored for 6 years. The risk of
      coronary events tended to be higher in patients with a serum total cholesterol
      (TC) > or =240 mg/dl compared with total cholesterol <240 mg/dl. The
      concentration of low-density lipoprotein cholesterol (LDL-C) positively
      correlated and that of high-density lipoprotein cholesterol (HDL-C) inversely
      correlated with the risk of CHD. Each 10 mg/dl decrease in LDL-C and each 10
      mg/dl increase in HDL-C concentration reduced the risk of CHD by 8.0% (95%
      confidence interval 3.8-12.0) and 28.3% (95% CI 13.9-40.3), respectively. A
      reasonable therapeutic strategy to reduce CHD progression in patients with prior
      CHD under low-dose statin treatment might be regulating the serum LDL-C
      concentration to at least <120 mg/dl and HDL-C >40 mg/dl, respectively.

PMID- 12499613
TI  - Prolongation of LAS40 (duration of the low amplitude electric potential component
      (<40 microV) of the terminal portion of the QRS) induced by isoproterenol in 11
      patients with Brugada syndrome.
AB  - The electrophysiological mechanism of Brugada syndrome is unclear, but transmural
      dispersion of repolarization in the right ventricle is believed to be the most
      likely mechanism. On the other hand, the presence of a conduction delay region is
      considered to be related to the occurrence of ventricular fibrillation; that is,
      a relationship between the presence of a ventricular late potential (LP) and
      arrhythmogenic right ventricular cardiomyopathy. In this study, the LP from
      signal-averaged electrocardiography during isoproterenol (ISP) administration in
      patients with Brugada syndrome is discussed. The subjects were 11 patients with
      Brugada syndrome and 6 healthy individuals. In all subjects, the total filtered
      QRS duration (fQRS), root mean square voltage of the 40 ms terminal portion of
      the QRS (RMS(40)), duration of the low amplitude electric potential component (40
      microV) of the terminal portion of the QRS (LAS(40)), and time duration of the
      fQRS-LAS(40) difference were compared between when ISP was prescribed and when it
      was not. During ISP administration, a peculiar response, which resulted in an
      LAS(40) prolongation, was observed in the patients with Brugada syndrome. With
      ISP, the fQRS remained unchanged, but the RMS(40) and the fQRS-LAS(40) decreased.
      Consequently another 3 patients with a positive LP were diagnosed using the
      ordinary standard because of the administration of ISP. We believe that the low
      amplitude component was unmasked by shortening of the high-amplitude component.
      In patients with Brugada syndrome, a conduction delay in the ventricle may be
      present and may be related to the occurrence of ventricular fibrillation.

PMID- 12499614
TI  - Correlation between thallium-201 myocardial perfusion defects and the functional
      severity of coronary artery stenosis as assessed by pressure-derived myocardial
      fractional flow reserve.
AB  - Although a relationship between the coronary pressure-derived fractional flow
      reserve (FFR) and the presence of myocardial ischemia as demonstrated by
      radionuclide imaging has been reported in a select group of patients, it remains
      to be established whether this relation also holds true in actual clinical
      settings with a heterogeneous group of patients. Accordingly, 194 coronary
      vessels and their supply territories were evaluated in 165 consecutive patients
      with suspected or known coronary artery disease. An FFR <0.75, which is regarded
      as indicative of functionally important stenosis, showed a significant
      correlation with the redistribution of (201)Tl (p<0.0001), with a sensitivity of
      79% and specificity of 73%. In 70 infarct-related coronary arteries, the
      sensitivity and specificity were 79% and 75%, respectively, whereas in the 124
      remaining vessels that were not related to the myocardial infarct, the
      sensitivity and specificity were 80% and 72%, respectively. In addition, the FFR
      exhibited a significant inverse correlation with the (201)Tl reversibility score
      (r=-0.62; p<0.0001). These results suggest that the FFR has a significant
      relationship with scintigraphic evidence of myocardial ischemia and can be
      regarded as a marker of its presence or absence in patients in actual clinical
      settings.

PMID- 12499615
TI  - Review of coronary artery disease in patients with infrarenal abdominal aortic
      aneurysm.
AB  - In the process of establishing a less invasive assessment strategy for coronary
      artery disease (CAD) in patients with infrarenal abdominal aortic aneurysm (AAA),
      the incidence of CAD and the surgical and mid-term outcomes were reviewed. From
      January 1994 through September 2001, 94 elective surgical repairs of AAA were
      carried out. Preoperative coronary angiography showed 43 patients (45.7%) had
      CAD: 29 (67.4%) were asymptomatic, 23 had single-vessel disease (1VD), 12 had 2VD
      and 8 had 3VD. Of the 43 patients with CAD, 19 (44.2%) underwent coronary
      interventional therapy before aortic surgery (11 percutaneous transluminal
      coronary angioplasty (PTCA), 8 coronary artery bypass grafting). Eight
      asymptomatic patients underwent coronary interventional therapy. None of the
      patients died of cardiac causes or experienced a postoperative cardiac event.
      During the follow-up period, 10 late deaths occurred: 7 patients with CAD, and 3
      cerebrovascular or cardiac deaths. There was no statistical difference in the
      survival rate between the groups with and without CAD. Two patients with CAD
      underwent PTCA during the follow-up period. The findings confirm the need for a
      less invasive assessment strategy of CAD that does not overlook asymptomatic
      myocardial ischemia, because the incidence of CAD in patients with AAA is high.

PMID- 12499616
TI  - Relation between transverse conduction capability and the anatomy of the crista
      terminalis in patients with atrial flutter and atrial fibrillation: analysis by
      intracardiac echocardiography.
AB  - Although crista terminalis (CT) has been identified as the barrier to transverse
      conduction during typical atrial flutter (AFL), the relation between transverse
      conduction capabilities and anatomy of the CT remains unclear. The aim of the
      study was to evaluate that relation using intracardiac echocardiography (ICE).
      Ten patients with typical AFL (group AFL), 7 patients with paroxysmal atrial
      fibrillation (PAF) (group AF) and 8 patients without PAF or AFL (group N)
      underwent electrophysiologic testing. Using ICE images, the maximum diameter of
      the short axis of the CT (dCT) was measured and mapping and pacing catheters were
      positioned precisely. From extrastimulation delivered 1-2 cm anteriorly (free
      wall) or posteriorly (posterior wall) to the CT, the effective refractory period
      (CT-ERP) was determined as the longest coupling interval that resulted in split
      potentials at the mapping catheter positioned along the CT, a finding consistent
      with a transverse conduction block at the CT. The dCT was greater in group AFL
      than in groups AF and N (5.0+/-0.8 vs 4.3 +/-0.7, p<0.05 and 4.2+/-0.4 mm,
      p<0.01, respectively). The CT-ERP was longer during pacing from the posterior
      wall than from the free wall (307+/-68 vs 266+/-29 ms, p<0.05) as a whole group.
      The CT-ERP for the posterior wall pacing was longer in group AFL than in group N
      (339+/-80 vs 255+/-13, p<0.05). CT-ERP did not correlate with dCT; however, dCT
      was greater in patients with split potentials at the CT than in patients without
      them (4.9 +/-0.8 vs 4.1+/-0.5 mm, p<0.05). Therefore, the transverse conduction
      block of CT was more likely to occur in a thick CT. A limited transverse
      conduction capability of the CT is related to its thickness and might contribute
      to the development of typical AFL.

PMID- 12499617
TI  - Effect of intracoronary nicorandil administration on preventing no-reflow/slow
      flow phenomenon during rotational atherectomy.
AB  - A major limitation of the rotational atherectomy (RA) procedure is the occurrence
      of the no-reflow/slow flow phenomenon and the optimal strategy is still evolving.
      Recent clinical studies have demonstrated the beneficial effects of nicorandil,
      an adenosine triphosphate (ATP)-sensitive potassium channel opener, on no-reflow
      in patients with acute myocardial infarction. The purpose of this study was to
      evaluate the effect of nicorandil on no-reflow/slow flow phenomenon during RA
      procedures. Sixty-one patients who underwent RA of complex coronary lesions were
      randomly divided into 2 groups: (i) nicorandil cocktail (n=24 patients, 37
      lesions) and (ii) verapamil cocktail (n=37 patients, 63 lesions). In each group,
      the drug cocktail mixed with pressurized saline was infused through the 4Fr
      Teflon sheath of the rotablator system during the RA procedure. In the nicorandil
      group, the drug cocktail consisted of 24 mg of nicorandil, 5 mg of nitroglycerin,
      and 10,000 U of heparin. In the verapamil group, the drug cocktail consisted of
      10 mg of verapamil, 5 mg of nitroglycerin, and 10,000 U of heparin. Baseline and
      procedure characteristics did not differ between the 2 groups. RA was performed
      successfully, and death, Q-wave myocardial infarction, or emergency coronary
      artery bypass surgery did not occur in any patients. The no-reflow/slow flow
      phenomenon was observed in 11/63 (17.4%) lesions of the verapamil group, but in
      only 1/37 (2.7%) lesions of the nicorandil group (p=0.03). No untoward
      complications were observed during nicorandil infusion. These data indicate that
      the intracoronary continuous infusion of nicorandil during RA procedures is easy
      and safe, and prevents no-reflow/slow flow phenomenon more effectively than
      infusion of verapamil.

PMID- 12499618
TI  - An incremental test to identify the pain threshold speed in patients with
      intermittent claudication.
AB  - The purpose of this study was to develop a test for identifying the speed of
      onset of claudication, or pain threshold speed (PTS), in 16 patients affected by
      intermittent claudication. An echo-Doppler examination and the ankle-brachial
      index (ABI) determination were also performed. Test repeatability was evaluated
      in 10 patients retested within a few days. All 16 patients underwent the
      incremental walking test 3 times during a 6-month rehabilitation training program
      to verify the test's sensitivity in detecting the expected functional
      modifications. PTS was identified in all patients examined and the test-retest
      correlation coefficient (R) for PTS was 0.98. During the 6-month rehabilitation
      period, the ABI rose from 0.43 +/-0.16 to 0.72+/-0.15 for the worst limb and PTS
      also rose significantly from 3.9+/-1.4 km/h to 6.1+/-1.1 km/h. The average
      increments of ABI and PTS were significantly correlated. An incremental walking
      test for the identification of the walking speed at which claudication occurs has
      been developed. The PTS is a reproducible parameter that can be combined with
      other test results to establish the severity of the disease and to check any
      modifications that occur during rehabilitation.

PMID- 12499619
TI  - Use of near-infrared spectroscopic measurement at the buttocks during abdominal
      aortic surgery.
AB  - During abdominal aortic surgery, dynamic changes occur in the pelvic circulation.
      Near-infrared spectroscopy (NIRS) was used in this study to evaluate arterial
      flow in the buttocks as a monitor of arterial flow in the pelvic area during
      abdominal aortic surgery. Twenty-two patients who underwent abdominal aortic
      aneurysmectomy comprised the study group. The NIRS probe was mounted on the left
      buttock during surgery, and the changes in oxy- and deoxy-hemoglobin (Hb)
      concentration were measured. In all cases Hb values reflected decreased arterial
      flow caused by aortic clamping and increased arterial flow after reconstruction
      of the distal arteries. The recovery pattern of the Hb values varied, but all
      recovered to the baseline value recorded before aortic clamping. None of the
      patients exhibited postoperative claudication of vessels supplying the gluteal
      muscles or colonic ischemia, and recovery time varied in accordance with the
      patient's arterial condition. This method is simple and enables individual
      evaluation of blood flow recovery from reconstructed arteries. This method allows
      approximate evaluation of the pelvic arterial flow of individual arteries, helps
      to predict postoperative claudication of the gluteal muscles, and offers
      additional information for evaluating colonic ischemia.

PMID- 12499620
TI  - Comparative study of dobutamine stress echocardiography and dual single-photon
      emission computed tomography (thallium-201 and I-123 BMIPP) for assessing
      myocardial viability after acute myocardial infarction.
AB  - Discordance between the (123)I-labelled 15-iodophenyl-3-R, S-methyl pentadecanoic
      acid (BMIPP) and (201)Tl findings may indicate myocardial viability (MV). This
      study compared dobutamine stress echocardiography (DSE) and single-photon
      emission computed tomography (SPECT) using the dual tracers for assessment of MV
      and prediction of functional recovery after acute myocardial infarction (AMI).
      DSE and dual SPECT were studied in 35 patients after AMI, of whom 28 underwent
      percutaneous coronary intervention in the acute stage. Dual SPECT was performed
      to compare the defect score of BMIPP and (201)Tl. The left ventricular wall
      motion score (WMS) was estimated during DSE and 6 months later to assess
      functional recovery of the infarct area. The rate of agreement of MV between dual
      SPECT and DSE was 89% (p<0.01), and the sensitivity and specificity of DSE for
      dual SPECT in MV assessment was 86% and 93%, respectively. The positive and
      negative predictive values for functional recovery by dual SPECT were 76% and
      67%, respectively, and by DSE were 90% and 79%, respectively. Four of 5 patients
      with positive MV by dual SPECT, but without functional recovery, had residual
      stenosis of the infarct-related artery. The WMS and defect scores of BMIPP and
      (201)Tl were significantly smaller in patients with functional recovery than in
      those without. Assessment of MV using DSE concords with the results of dual SPECT
      in the early stage of AMI. DSE may have a higher predictive value for long-term
      functional recovery at the infarct area. However, a finding of positive MV by
      dual SPECT, without functional recovery, may indicate residual stenosis of the
      infarct-related artery, although the number of cases was small. Combined
      assessment by dual SPECT and DSE may be useful for detecting MV and jeopardized
      myocardium. Furthermore, the results suggest that functional recovery of
      dysfunctional myocardium may depend on the size of the infarct and risk area.

PMID- 12499621
TI  - Use of thallium-201 myocardial scintigraphy for the prediction of the response to
      beta-blocker therapy in patients with dilated cardiomyopathy.
AB  - This study was performed to evaluate whether thallium-201 myocardial scintigraphy
      (Tl-201) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy
      could predict the usefulness of beta-blocker therapy in patients with dilated
      cardiomyopathy (DCM). Tl-201 and MIBG were performed in 47 patients before beta
      blocker therapy. Patients were classified into group A, if their cardiac function
      improved, and group B, whose function remained unchanged. Two types of extent
      score (ES) by Tl-201 were proposed to quantitate myocardial damage, mean-2SD (ES
      2) and mean-3SD (ES-3). The ES difference between ES-2 and ES-3 was calculated,
      and according to ES and ES difference, DCM cases were classified into 3 groups:
      mild-defect type (mild-type), moderate-defect type (moderate-type) and severe
      defect type (severe-type). The heart-to-mediastinum (H/M) MIBG uptake ratio was
      evaluated, and the percent washout ratio of myocardial MIBG was obtained from
      these data. Group A comprised 18 mild-type, 14 moderate-type and 1 severe-type
      cases, and group B comprised 5 mild-type, 4 moderate-type and 5 severe-type
      cases. A significant relation was observed between the defect type on Tl-201 and
      the response to beta-blocker therapy (p=0.0090). Both H/M MIBG uptake ratios and
      washout ratio were not significantly different in the 2 groups. Tl-201 may be
      useful for predicting the response to beta-blocker therapy in patients with DCM.

PMID- 12499622
TI  - Increasing mortality from pulmonary embolism in Japan, 1951-2000.
AB  - In the United States, annual mortality rates from pulmonary embolism (PE) tended
      to increase from the 1960s to the mid 1980s, but thereafter began to decrease. In
      Japan, PE is not yet widespread and there have not been any reports of the time
      trend of its mortality rate. The present study calculated the annual age-adjusted
      and age-specific PE mortality rates for Japanese residents during 1951 to 2000
      from the 'Vital Statistics of Japan' and the census data and population estimates
      for the intercensal years. Throughout the study period, the age-adjusted deaths
      and mortality rates from PE continued to increase, and between 1976 and 1996 the
      increases in the annual age-specific mortality rates were substantial in males 45
      49 years of age and 55 years or older, and in females 30 years of age or older.
      The age-specific PE death rates increased throughout the life span in general and
      according to the decade. Male mortality was greater at most ages. In Poisson
      regression analysis, the relative risk of death from PE was increased in males,
      the aged, and in recent years. Overall, mortality from PE in Japan increased
      significantly during 1951 to 2000.

PMID- 12499623
TI  - Cardiovascular and adenylate cyclase stimulating effects of colforsin daropate, a
      water-soluble forskolin derivative, compared with those of isoproterenol,
      dopamine and dobutamine.
AB  - Colforsin daropate is a recently developed water-soluble derivative of forskolin
      that directly stimulates adenylate cyclase, unlike the catecholamines. The
      chronotropic, inotropic and coronary vasodilator actions of colforsin daropate
      were compared with those of isoproterenol, dopamine and dobutamine, using canine
      isolated, blood-perfused heart preparations. The stimulating effect of each drug
      on adenylate cyclase activity was also assessed. Colforsin daropate, as well as
      each of the catecholamines, exerted positive chronotropic, inotropic and coronary
      vasodilator actions. The order of selectivity for the cardiovascular variables of
      colforsin daropate was coronary vasodilation >> positive inotropy > positive
      chronotropy; whereas that of isoproterenol, dopamine and dobutamine was positive
      inotropy >> coronary vasodilation > positive chronotropy. Thus, a marked
      characteristic of colforsin daropate is its potent coronary vasodilator action.
      On the other hand, each drug significantly increased the adenylate cyclase
      activity in a dose-related manner: colforsin daropate >> isoproterenol > dopamine
      = dobutamine. These results suggest that colforsin daropate may be preferable in
      the treatment of severe heart failure where the coronary blood flow is reduced
      and beta-adrenoceptor-dependent signal transduction pathway is down-regulated.

PMID- 12499624
TI  - Short polymers of arginine rapidly translocate into vascular cells: effects on
      nitric oxide synthesis.
AB  - The present study was designed to determine the efficiency of translocation of
      short polymers of arginine into vascular smooth muscle cells (VSMC) and to
      determine their effect on nitric oxide (NO) synthesis. Immunostaining revealed
      that heptamers of L-arginine (R7) rapidly translocated into the VSMC. This rapid
      transport was not observed with shorter polymers of L-arginine (R5) nor heptamers
      of lysine (K7). Translocation of R7 was not inhibited by the addition of free L
      arginine into the media. When cells were transiently pretreated with R7 or a
      nonamer of arginine (R9), NO(2) production from cytokine stimulated VSMC was
      significantly increased, whereas incubation with R5 and K7 had no effect. Short
      polymers of arginine not only have a unique ability of rapid VSMC translocation
      but once internalized enhance NO production. Heptamers (or larger polypeptides)
      of arginine may be useful in therapy to enhance NO production in the vascular
      system.

PMID- 12499625
TI  - Arrhythmogenic and inotropic effects of interferon investigated in perfused and
      in vivo rat hearts: influences of cardiac hypertrophy and isoproterenol.
AB  - Although the arrhythmogenic effects of interferon (IF) have been reported in
      clinical practice, the experimental data are limited. Therefore, these effects
      were investigated in in vivo and Langendorff-perfusion studies using 3 different
      groups of rats (ie, control, aorta-banded, and deoxycorticosterone acetate (DOCA)
      salt hypertension groups) in the presence or absence of isoproterenol. In the
      perfusion study, human recombinant IF-alpha (< or =15,000 U/ml) alone induced
      irreversible atrioventricular blockade in all groups, whereas this agent (< or
      =1,500 U/ml) caused negative inotropism and ventricular tachyarrhythmias
      (arrhythmic score greater in the order of DOCA-salt>aorta-banded = control group)
      in the preparations pretreated with isoproterenol (10(-9) mol/L). In an in vivo
      study, IF-alpha (6x10(6) U/kg) resulted in ventricular tachyarrhythmias only in
      the presence of isoproterenol (10 mg/kg), as in the perfusion study (arrhythmic
      score; DOCA-salt>aorta-banded>control). In conclusion, the arrhythmogenesis of IF
      alpha is potentiated in pathophysiological conditions such as cardiac hypertrophy
      or elevated sympathetic activity.

PMID- 12499626
TI  - Left and right coronary circulation in left ventricular hypertrophy: effects of
      angiotensin converting enzyme inhibition.
AB  - The circulation in the left and right coronary beds in pressure overload-induced
      left ventricular (LV) hypertrophy was studied in Wistar male rats (n=6/group)
      that were subjected to abdominal aortic constriction or to sham-operation. From 3
      to 6 weeks after surgery, the animals with aortic constriction received vehicle
      or 0.01, 0.1, or 1 mg/kg per day po of the angiotensin converting enzyme (ACE)
      inhibitor, ramipril. At 6 weeks, after measuring blood pressure in the carotid
      artery in vivo, the hearts were isolated and the left and right coronary beds
      subjected to independent perfusion. Minimum coronary vascular resistance per unit
      heart weight (MCVR/g) was determined in both beds during simultaneous infusion of
      10 micromol/L adenosine. Aortic constriction resulted in a significant increase
      in blood pressure, LV weight/body weight ratio, and bilateral MCVR/g. Ramipril
      lowered arterial pressure in a dose-dependent manner and reversed the increased
      right MCVR/g at the anti-hypertensive dose, but it did not affect LV mass or left
      MCVR/g. These results suggest that both coronary hypertension and myocardial
      hypertrophy contribute to the global impairment of coronary circulation in LV
      hypertrophy. ACE inhibitors may improve coronary circulation in LV hypertrophy
      when administrated at an appropriate dose and for a sufficient period.

PMID- 12499627
TI  - Attenuation of biventricular pressure gradients by cibenzo-line in an 18-year-old
      patient with hypertrophic obstructive cardiomyopathy.
AB  - An 18-year-old male patient with biventricular hypertrophic obstructive
      cardiomyopathy (HOCM) had successful reduction of the pressure gradients by
      cibenzoline. At 11 months after birth, he was first diagnosed with cardiac
      murmurs and by the age of 5 years, he was diagnosed with subpulmonic infundibular
      stenosis with a pressure gradient of 10 mmHg by cardiac catheterization. At the
      age of 14, re-catherterization revealed hypertrophic cardiomyopathy with isolated
      obstruction of the right ventricular outflow tract, with a pressure gradient of
      70 mmHg, but no obstruction in the left ventricle. He began daily treatment with
      30 mg propranolol. At the age of 18, he was admitted for cardiac evaluation. An
      echocardiogram revealed left mid-ventricular and subpulmonic obstructions
      associated with pressure gradients of 88 mmHg and 65 mmHg, respectively. A single
      oral dose of 200 mg of cibenzoline decreased the pressure gradients in the left
      and right ventricles (38 mmHg and 36 mmHg, respectively). He was then given 300
      mg daily of cibenzoline, and both pressure gradients remained low without any
      complications 8 months later at the time of discharge.

PMID- 12499628
TI  - Surgical treatment of a descending aortic aneurysm in a patient with noncirrhotic
      portal hypertension and a portal systemic shunt.
AB  - A 63-year-old male with atrial fibrillation and mild mitral valve regurgitation
      was referred to hospital because of a descending aortic aneurysm. During the
      evaluation, he developed an encephalopathy because of hyperammoniaemia. Further
      examination revealed a portal systemic shunt, perhaps caused by the noncirrhotic
      portal hypertension. The patient underwent successful replacement of the aneurysm
      after controlling the blood ammonia level by eliminating protein from the diet
      and removal of nitrogen from the gastrointestinal tract. Cardiovascular surgery
      in a patient with noncirrhotic portal hypertension and a portal systemic shunt
      has not been previously reported. Meticulous management of the perioperative
      blood ammonia concentration is essential.

PMID- 12499629
TI  - Noninvasive diagnosis of partial atrial standstill using magnetocardiograms.
AB  - A 59-year-old woman with partial atrial standstill was studied using
      magnetocardiograms (MCGs), which revealed through QRS-T subtraction and time
      frequency analysis that there was a high-frequency (6 Hz) magnetic source at the
      low atrial septum. MCGs are useful for noninvasively evaluating the clinical
      course of patients with atrial fibrillation.

PMID- 12499630
TI  - Effect of intravenous propranolol on left ventricular apical ballooning without
      coronary artery stenosis (ampulla cardiomyopathy): three cases.
AB  - The precise etiological basis of transient left ventricular apical ballooning
      without coronary artery stenosis (ampulla or so-called 'takotsubo'
      cardiomyopathy) remains unknown, so the present study examined the acute effects
      of intravenous propranolol (2-4 mg) in 3 female patients (age range, 61-76 years)
      with the condition. Although one patient who did not have any intraventricular
      pressure gradients showed no improvement in the electrocardiographic and left
      ventricular wall motion abnormalities, the other 2 patients, who had significant
      intraventricular pressure gradients, did show improvement. Dynamic
      intraventricular obstruction might play a role in maintaining apical ballooning,
      at least, in patients exhibiting an intraventricular pressure gradient.

PMID- 12499631
TI  - Neuroprotective effects of the green tea components theanine and catechins.
AB  - The neuroprotective effects of theanine and catechins contained in green tea are
      discussed. Although the death of cultured rat cortical neurons was induced by the
      application of glutamic acid, this neuronal death was suppressed with exposure to
      theanine. The death of hippocampal CA1 pyramidal neurons caused by transient
      forebrain ischemia in the gerbil was inhibited with the ventricular
      preadministration of theanine. The neuronal death of the hippocampal CA3 region
      by kainate was also prevented by the administration of theanine. Theanine has a
      higher binding capacity for the AMPA/kainate receptors than for NMDA receptors,
      although the binding capacity in all cases is markedly less than that of glutamic
      acid. The results of the present study suggest that the mechanism of the
      neuroprotective effect of theanine is related not only to the glutamate receptor
      but also to other mechanisms such as the glutamate transporter, although further
      studies are needed. One of the onset mechanisms for arteriosclerosis, a major
      factor in ischemic cerebrovascular disease, is probably the oxidative alteration
      of low-density lipoprotein (LDL) by active oxygen species. The oxidative
      alterations of LDL were shown to be prevented by tea catechins. Scavenging of
      *O(2)(-) was also exhibited by tea catechins. The neuroprotective effects of
      theanine and catechins contained in green tea are a focus of considerable
      attention, and further studies are warranted.

PMID- 12499632
TI  - Characterization of the surface activity of a synthetic surfactant with albumin.
AB  - We previously reported that a human analogue of pulmonary surfactant protein-C
      (SP-C), SP-CL16 (6-28), with 23 residues was the most active analogue in a
      reconstituted lipid mixture and had the shortest chain among the poly leucine
      analogues examined. In this study, we verified the influence of albumin, a
      component of serum, on the surface activity of surfactant. Surface activity was
      measured using the Langmuir-Wilhelmy surface balance (WSB), pulsating bubble
      surfactometer (PBS), and stable microbubble test (MBT). The surface activity of
      synthetic lung surfactant (SLS) was only slightly influenced by albumin (0.1-10
      mg/ml) as compared with that of a ternary mixture of phospholipids. The ternary
      mixture of phospholipids showed a decrease in surface activity due to albumin. In
      particular, SLS did not show interaction of surface activity with albumin in
      vitro (WSB, PBS, and MBT). In contrast,
      dipalmitoylphosphatidylcholine/phosphatidylglycerol/palmitic acid had
      significantly weaker surface activity in the presence of albumin. Surfactant-TA
      showed interaction of surface activity with albumin in the MBT. The number of
      stable microbubble increased in the presence of albumin at a concentration of 0.1
      mg/ml.

PMID- 12499633
TI  - Stimulation of 14-3-3 protein and its isoform on histamine secretion from
      permeabilized rat peritoneal mast cells.
AB  - The effect of the 14-3-3 protein, an adaptor protein of intracellular signal
      pathways, on histamine release from rat peritoneal mast cells was investigated.
      The exogenous 14-3-3 protein from bovine brain increased the Ca(2+)-dependent
      histamine release from permeabilized mast cells, but only slightly affected the
      non-permeabilized cells. Partial amino acid sequences showed that the bovine
      brain 14-3-3 protein contained 14-3-3beta, gamma and zeta isoforms, and that
      these recombinant isoforms were prepared. Among them, 14-3-3zeta was an active
      species while the 14-3-3beta and gamma were inactive for histamine release from
      the permeabilized mast cells. Approximately 15% of the histamine release was
      stimulated by 14-3-3zeta at 2.5 microM, and half-maximal stimulation occurred at
      1 microM. Treatment of the mast cells with wortmannin or staurosporine completely
      inhibited the stimulatory effect on histamine release caused by Ca(2+) or
      Ca(2+)/14-3-3zeta, and genistein partially inhibited both stimulatory effects. PD
      98059, however, had little effect on the histamine release. These results suggest
      the possibility that 14-3-3zeta is associated with signal transduction for
      degranulation of the mast cells.

PMID- 12499634
TI  - Analysis of the gene encoding copper/zinc superoxide dismutase homolog in
      Dictyostelium discoideum.
AB  - SodD, a Cu/Zn superoxide dismutase in Dictyostelium discoideum, shows 48%
      identity to the cytosolic Cu/Zn superoxide dismutase (SOD) of Saccharomyces
      cerevisiae (SOD1). The sodD gene is expressed in D. discoideum cells at late
      developmental stages. However, gene expression was not detected in the sporeless
      mutant, indicating that sodD is a spore cell-specific gene. The D. discoideum
      mutant, in which sodD was disrupted, grew and formed a multicellular structure
      normally, therefore the gene is not essential for growth and development. The
      mutant spores were sensitive to UV-light compared to the wild-type spores,
      indicating that SodD protects spores from cellular damage caused by UV-light.

PMID- 12499635
TI  - Cloning and characterization of a novel chromosomal drug efflux gene in
      Staphylococcus aureus.
AB  - A novel drug efflux gene (named sepA, staphylococcal efflux pump gene) is cloned
      from antiseptic-resistant mutants of Staphylococcus aureus into Escherichia coli.
      The sepA gene conferred the reduction of susceptibility to acriflavine and the
      acceleration of ethidium bromide efflux from the E. coli cells. The sepA (474 bp)
      encoded the protein that has four predicted transmembrane segments. These results
      indicate that sepA gene is a multidrug-resistant gene and encodes a drug efflux
      protein.

PMID- 12499636
TI  - Humanization of the mouse anti-Fas antibody HFE7A and crystal structure of the
      humanized HFE7A Fab fragment.
AB  - Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system plays
      important roles in many biological processes, including the elimination of
      autoreactive lymphoid cells. We have previously obtained the mouse anti-Fas
      antibody HFE7A (m-HFE7A), which specifically induces apoptosis in inflammatory
      cells. In order to apply m-HFE7A for human therapy, we performed antibody
      humanization of m-HFE7A by grafting the mouse complementarity-determining regions
      (CDRs) to a human antibody. Five versions of humanized HFE7A (h-HFE7A)
      demonstrated the same antigen-binding affinity and same competition-binding
      activity against Fas as the chimeric HFE7A. Furthermore, these h-HFE7As induced
      the same degree of apoptosis in WR19L12a cells that express human Fas on their
      surface as chimeric HFE7A does. To further probe the structural basis for
      antibody humanization, we determined the three-dimensional structure of the h
      HFE7A antigen-binding fragment (Fab) by X-ray crystallography and compared it
      with the crystal structure of the parent m-HFE7A Fab previously determined. The
      main-chain conformation in each h-HFE7A CDR is almost identical to that in m
      HFE7A with root mean square (rms) deviations of 0.14-0.77 A. However, a
      significant segmental shift was observed in the CDR-L1 loop. Together with the
      high temperature factors of the CDR-L1 residues, both the loops are flexible,
      suggesting that the CDR-L1 loop would undergo conformational change upon binding
      to the antigen. Our results indicate that the humanization of m-HFE7A succeeded
      in maintaining the main-chain conformation as well as the flexibility of the CDR
      loop.

PMID- 12499637
TI  - Magnolol has the ability to induce apoptosis in tumor cells.
AB  - We previously found that multiple intraperitoneal administration of magnolol from
      Magnolia obovata inhibited tumor metastasis and growth in vivo, and that the anti
      metastatic effect of magnolol was due to the inhibition of the tumor cell
      invasion. The purpose of this study was to clarify the inhibitory mechanism of
      magnolol on the growth of tumor cells, and we expect that magnolol may have the
      ability to induce apoptosis in tumor cells. In an in vitro proliferation assay,
      100 microM of magnolol inhibited the proliferation of B16-BL6, THP-1, BAE and HT
      1080 cells, but 30 microM of magnolol did not affected cells proliferation. In
      addition, 100 microM of magnolol induced apoptotic cell death within 24 h in
      three tumor cell lines, B16-BL6, THP-1 and HT-1080, not BAE cells, and then up
      regulated the activity of caspase-3 and caspase-8. The up-regulation of caspases
      activity by 100 microM of magnolol was suppressed by the inhibitor of all
      caspases, z-VAD-fmk. These data suggest that magnolol possesses ability to
      inhibit tumor growth, and the ability is due to the induction of apoptosis with
      the activation of caspases.

PMID- 12499638
TI  - Ginseng radix increases cell proliferation in dentate gyrus of rats with
      streptozotocin-induced diabetes.
AB  - In the present study, the effect of Ginseng radix on cell proliferation in the
      dentate gyrus of rats with streptozotocin-induced diabetes was investigated via
      immunohistochemistry. Aqueous extract of Ginseng radix was shown to exert no
      significant effect on weight in normal rats, while it prevented weight loss in
      rats with streptozotocin-induced diabetes. Cell proliferation in the dentate
      gyrus of diabetic rats was increased by Ginseng radix treatment, but it had no
      effect on cell proliferation in normal rats. These results suggest that Ginseng
      radix may help in improve the central nervous system complications of diabetes
      mellitus.

PMID- 12499639
TI  - Modulation of multidrug resistance by artemisinin, artesunate and
      dihydroartemisinin in K562/adr and GLC4/adr resistant cell lines.
AB  - Overcoming MDR (multidrug resistance) phenomena is a crucial aspect of cancer
      chemotherapy research. Artemisinin and its derivatives have been found to inhibit
      the proliferation of cancer cells in the microM range. They poorly inhibited the
      function of P-glycoprotein and did not inhibit the function of MRP1-protein. The
      concentrations required to inhibit by 50% the function of P-glycoprotein are
      110+/-5 microM. Artemisinin, artesunate and dihydroartemisinin efficiently
      decreased the mitochondrial membrane potential, leading to a decrease in
      intracellular ATP in all cell lines tested: by 30 to 50% at 5 microM.
      Artemisinin, artesunate and dihydroartemisinin increased cytotoxicity of
      pirarubicin and doxorubicin in P-glycoprotein-overexpressing K562/adr, and in
      MRP1-overexpressing GLC4/adr, with the delta(0.5) ranging from 200 to 860 nM, but
      not in their corresponding drug-sensitive cell lines. In this range of
      concentrations these compounds did not decrease the function of P-glycoprotein,
      suggesting a mechanism by which the drugs did not reverse MDR phenomenon at the P
      glycoprotein level but at the mitochondrial level.

PMID- 12499640
TI  - Pharmacological characteristics of Ryokan-kyomi-shinge-nin-to, an antiallergic
      Kampo medicine.
AB  - The pharmacological characteristics of Ryokan-kyomi-shinge-nin-to (RKS), a
      traditional oriental herbal (Kampo) medicine which has been used for the
      treatment of allergic asthma and rhinitis, were investigated. The number of
      sneezes by actively sensitized mice after a topical antigen challenge was
      significantly reduced by pretreatment with RKS (300 and 1000 mg/kg, p.o.).
      Although RKS did not inhibit the antigen-induced histamine release from rat
      peritoneal exudate cells (PEC), it significantly inhibited an increase in
      vascular permeability induced by histamine and serotonin. These results suggest
      that RKS has antiallergic activity in animals, and the functional antagonism of a
      histamine response may be one of the mechanisms of its effect. In addition, RKS
      prevented histamine hypersensitivity in actively sensitized mice. Because RKS did
      not affect sleeping time induced by pentobarbital in mice and did not inhibit
      gastric emptying in rats, the drug appears to be useful for treating allergic
      patients suffering from classical antihistamines side effects such as stomach
      discomfort or relative drowsiness.

PMID- 12499641
TI  - Aromatase inhibition by 4 beta,5 beta-epoxides of 16 alpha-hydroxyandrostenedione
      and its 19-oxygenated analogs, potential precursors of estriol production in the
      feto-placental unit.
AB  - To gain insight into the nature of the substrate binding site and the catalytic
      function of aromatase, we studied the inhibition of androstenedione aromatization
      by 4beta,5beta-epoxy-16alpha-hydroxyandrostenedione (4) and its 19-hydroxy and 19
      oxo derivatives, 5 and 6, as well as the biochemical aromatization of these
      steroids in human placental microsomes. The 19-methyl and 19-oxo compounds, 4 and
      6, were weak competitive inhibitors of aromatase, with apparent K(i) values of
      246 microM and 270 microM, respectively, whereas the 19-hydroxy compound 5
      inhibited aromatase in a non-competitive manner with the K(i) of 135 microM. The
      19-methyl compound 4 inactivated aromatase in a time-dependent manner with
      k(inact) of 0.213 min(-1) in the presence of NADPH in air, but the other two did
      not cause it. The conversion of the three epoxides into estrogen, as well as 19
      oxygenation of 19-methyl steroid 4 with human placental microsomes in the
      presence of NADPH in air, were not detected by gas chromatography-mass
      spectrometry. The present results are consistent with the two binding sites
      theory in the active site of aromatase.

PMID- 12499642
TI  - The pharmacological characterization of attentional processes using a two-lever
      choice reaction time task in rats.
AB  - Activating the noradrenergic and cholinergic systems is known to enhance
      attentional processes, while stimulating dopaminergic, serotonergic, and
      GABAergic systems suppresses them. The objective of the present study was to
      investigate the pharmacological characterization in the attentional processes of
      a two-lever choice reaction time (CRT) task using different centrally acting
      drugs. We designed seven parameters in this task: the correct response (CR) rate;
      error response rate; nonresponse (NR) rate; differential reinforcement of other
      behavior (DRO) responses; number of incorrect lever pressings during both the
      intertrial interval and DRO periods; the mean CRT of CR; and activity during 30
      trials. The compounds produced different profiles at each dose. 1) Facilitative
      and disruptive effects on attentional processes occurred with changes in CRT
      alone. Scopolamine (0.1 mg/kg) and prazosin (0.3-1 mg/kg) prolonged the CRT,
      whereas methamphetamine (0.3 mg/kg) shortened the CRT. 2) Attentional deficits
      occurred with abnormal behavior showing premature response or perseverative
      behavior. Scopolamine (0.2-1 mg/kg), methamphetamine (3 mg/kg), delta(9)
      tetrahydrocannabinol (10 mg/kg), and MK-801 (0.1-0.3 mg/kg) produced a marked
      increase in the number of total lever pressings. 3) Motor function deficits
      rather than attentional deficits occurred. 8-OH DPAT (1 mg/kg) and muscimol (1
      mg/kg) produced a decrease in CR and an increase in NR with a marked decrease in
      activity and prolonged the CRT. Activating noradrenergic alpha(1) receptors was
      found to enhance the attentional processes, while blocking muscarinic receptors,
      alpha(1) receptors, and NMDA receptors, and stimulating cannabinoid receptors and
      the dopaminergic systems impaired the attentional processes in the two-lever CRT
      task.

PMID- 12499643
TI  - Inhibition of cholesterol synthesis causes both hypercholesterolemia and
      hypocholesterolemia in hamsters.
AB  - Effects of FR194738 ((E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2
      (3-thienylmethoxy)propyloxy]benzylamine hydrochloride), a squalene epoxidase
      inhibitor, on lipid metabolism were compared with those of pravastatin, a 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in hamsters.
      Drugs were given for 10 d either as a diet mixture or as a bolus oral gavage, and
      similar results were obtained with each type of administration. FR194738 (0.01
      0.32% as a diet mixture; 10-100 mg/kg as an oral gavage) dose-dependently
      decreased serum total cholesterol, non high density lipoprotein (HDL)
      cholesterol, HDL cholesterol and triglyceride levels, and the changes in serum
      parameters were similar. Pravastatin (0.01-0.32% as a diet mixture; 1-100 mg/kg
      as an oral gavage) increased serum cholesterol levels, and dose-dependently
      decreased serum triglyceride levels. Although oral gavage of FR194738 at 32 mg/kg
      and pravastatin at 3.2 and 10 mg/kg increased hepatic HMG-CoA reductase activity,
      the degree of the changes was far greater with the latter than the former drug.
      FR194738 slightly increased hepatic cholesterol content at 32 mg/kg, whereas
      pravastatin dose-dependently increased hepatic cholesterol content until it
      leveled off at 32 and 100 mg/kg. It is concluded that inhibition of squalene
      epoxidase and HMG-CoA reductase triggers both hypercholesterolemic (hepatic
      cholesterol synthesis) and hypocholesterolemic (hepatic cholesterol uptake)
      mechanisms. FR194738 appears to induce a greater enhancement of the latter rather
      than the former, whereas pravastatin has a greater effect on the former.

PMID- 12499644
TI  - Uptake of liposomally entrapped fluorescent antisense oligonucleotides in NG108
      15 cells: conventional versus pH-sensitive.
AB  - Antisense oligodeoxynucleotides (asODN) are novel therapeutic agents designed to
      alter RNA metabolism, ultimately resulting in decreased production of disease
      associated gene products. To investigate internalisation of liposomally delivered
      asODN in NG108-15 cells, a hybrid cell line of mouse neuroblastoma and rat
      glioma, and assure that uptake of marker corresponds to that of antisense, we
      compared the cellular uptake of fluorescently labelled marker (fluorescein
      isothiocyanate (FITC)-dextran) and antisense oligonucleotide (FITC-asODN),
      entrapped either in conventional soy phosphatidylcholine (SPC) liposomes or pH
      sensitive liposomes (composed of dioleoylphosphatidylethanolamine and cholesteryl
      hemisuccinate in a molar ratio of 3 : 2). Both SPC and pH-sensitive liposomes
      were prepared by a modified freeze-thawing method. Entrapment efficiencies (about
      20% of the original material) did not depend on the liposome compositions and
      fluorescent material used. Fluorescence activated cell sorting (FACS) analysis
      was used to quantify the association of fluorescent material with the NG108-15
      cells, whereas confocal microscopy gave insight on the location of cell
      associated-fluorescence. Conventional liposomes failed to deliver fluorescent
      material into the cells, but in contrast, pH-sensitive liposomes significantly
      improved the uptake of both FITC-dextran and FITC-asODN, with the uptake of
      liposomal FITC-dextran being greater than the uptake of liposomal FITC-asODN.
      These results suggest that pH-sensitive liposomes can be applied as a carrier
      system in the delivery of genetic material into the cells.

PMID- 12499645
TI  - Mechanical stretch-induced mitogen-activated protein kinase activation is
      mediated via angiotensin and endothelin systems in vascular smooth muscle cells.
AB  - We previously reported that pressure loading of the vascular wall can activate
      mitogen-activated protein kinases (MAPKs), enzymes believed to be involved in the
      pathway for cell proliferation, partly via the vascular angiotensin system in
      isolated perfused rat aorta. In this study, we examined whether cyclic stretching
      of vascular smooth muscle cells (VSMC) also produces activation of p42 and p44
      MAPKs in cultured rat VSMC and whether stretch-induced MAPK activation is
      mediated via angiotensin and endothelin systems in VSMC. Cyclic stretching of
      VSMC produced an elongation-dependent and frequency-dependent increase in p42 and
      p44 MAPK activity. The stretch-induced p42 and p44 MAPK activation was inhibited
      by the angiotensin receptor antagonist losartan and by the angiotensin-converting
      enzyme inhibitor, captopril. The MAPK activation was also inhibited by the
      endothelin receptor antagonist cyclo(D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D
      tryptophyl) (BQ123) and by the endothelin-converting enzyme inhibitor
      phosphoramidon. Replacement of medium with culture medium of stretched cells
      caused MAPK activation, which was inhibited by losartan and BQ123. The results of
      the present study suggest that cyclic stretching of VSMC can activate p42 and p44
      MAPKs and that the MAPK activation is mediated via angiotensin and endothelin
      systems in VSMC.

PMID- 12499646
TI  - Sequence analysis of Chinese and Japanese Curcuma drugs on the 18S rRNA gene and
      trnK gene and the application of amplification-refractory mutation system
      analysis for their authentication.
AB  - The botanical origins of Chinese and Japanese Curcuma drugs were determined to be
      Curcuma longa, C. phaeocaulis, the Japanese population of C. zedoaria, C.
      kwangsiensis, C. wenyujin, and C. aromatica based on a comparison of their 18S
      rRNA gene and trnK gene sequences with those of six Curcuma species reported
      previously. Moreover, to develop a more convenient identification method,
      amplification-refractory mutation system (ARMS) analysis of both gene regions was
      performed on plants. The ARMS method for the 18S rRNA gene was established using
      two types of forward primers designed based on the nucleotide difference at
      position 234. When DNAs of four Curcuma species were used as templates, PCR
      amplification with either of the two primers only generated a fragment of 912
      base pairs (bp). However, when DNAs of the purple-cloud type of C. kwangsiensis
      and C. wenyujin were used, PCR amplifications with both primers unexpectedly
      generated the fragment, suggesting that these two were heterozygotes. The ARMS
      method for the trnK gene was also established using a mixture of four types of
      specific reverse primers designed on the basis of base substitutions and indels
      among six species, and common reverse and forward primers. C. phaeocaulis or the
      Chinese population of C. zedoaria, the Japanese population of C. zedoaria or the
      purple-cloud type of C. kwangsiensis, the pubescent type of C. kwangsiensis or C.
      wenyujin, and C. aromatica were found to show specific fragments of 730, 185, 527
      or 528, and 641 or 642 bp, respectively. All species including C. longa also
      showed a common fragment of 897-904 bp. Using both ARMS methods, together with
      information on producing areas, the identification of Curcuma plants was
      achieved. Moreover, the ARMS method for the trnK gene was also useful for
      authentication of Curcuma drugs.

PMID- 12499647
TI  - Evaluation of the cytotoxicity effect of dimethyl sulfoxide (DMSO) on Caco2/TC7
      colon tumor cell cultures.
AB  - Dimethyl sulfoxide (DMSO) is usually used to solubilize poorly soluble drugs in
      permeation assays such as that using Caco2 enterocyte-like cells. The objective
      of this study was to evaluate the toxicity of DMSO on Caco2/TC7 cells and
      determinate the maximal concentration usable in permeation experiments. Caco2/TC7
      cells were cultured for 21 d on 96-well plates for evaluation of toxicity. The
      determination of lactate dehydrogenase (LDH) release in cell supernatant and the
      measurement of Neutral Red (NR) uptake are used for cytotoxicity assays. DMSO
      solutions (0-100%) in Hank's balanced salt solution containing HEPES (25 mM), pH
      7.4, were incubated with Caco-2/TC7 cells on 96 well plates. Caco2/TC7 cells were
      cultured on Transwell-Clear inserts to evaluate the influence of DMSO on the
      apparent permeability of the paracellular marker mannitol. DMSO 10% did not
      induce any significant increase in LDH release whereas a significant increase in
      LDH activity (ANOVA, p<0.05) occurred at a DMSO concentration of 20 to 50%. NR
      incorporation in viable cells was statistically reduced by 27 to 36% at DMSO
      concentration of 20% up to 100% (ANOVA, p>0.05). No statistical difference
      (p<0.05) in apparent mannitol permeability was observed between the control and
      10% DMSO groups. In conclusion, at concentrations of up to 10%, DMSO did not
      produce any significant alteration in apical membrane permeability or on cell-to
      cell tight junctional complexes.

PMID- 12499648
TI  - MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs.
AB  - The multidrug transporter, MDR1-mediated interaction of digoxin with
      antiarrhythmic or antianginal drugs was examined in vitro by using the MDR1
      overexpressing LLC-GA5-COL150 cells, which were established by transfection with
      human MDR1 cDNA into porcine kidney epithelial LLC-PK(1) cells. Amiodarone, its
      active metabolite monodesethyl-amiodarone (DEA), and quinidine markedly inhibited
      the basal-to-apical transport (renal secretion) of [(3)H]digoxin and increased
      the apical-to-basal transport (reabsorption), but cibenzoline and lidocaine
      showed slight inhibition of the transport, and disopyramide and mexiletin had no
      such effects. The IC(50) values for amiodarone, DEA and quinidine on
      [(3)H]digoxin transport in LLC-GA5-COL150 cells were 5.48 microM, 1.27 microM and
      9.52 microM, respectively. These were comparable to, or only several times the
      achievable concentration in clinical use, suggesting that MDR1 could be
      responsible for the drug interaction between digoxin and amiodarone found in
      clinical reports and that DEA contributes the elevation of digoxin serum
      concentration. Similarly, dipyridamole altered the transport, but isosorbide
      showed only slight modification of the transport. The IC(50) value for
      dipyridamole was 40.0 microM, also only several times the achievable
      concentration in clinical use, indicating a risk of interaction.

PMID- 12499649
TI  - Permeation-enhancing effect of aloe-emodin anthrone on water-soluble and poorly
      permeable compounds in rat colonic mucosa.
AB  - The aims of this study were to examine the enhancing effects of aloe-emodin
      anthrone (AEA) on the colonic membrane permeability of water-soluble and poorly
      permeable compounds and to clarify the mechanism of the permeation-enhancing
      activity of AEA. The permeation-enhancing activity of AEA was estimated from
      changes in the permeability coefficient of 5(6)-carboxyfluorescein (CF) in rat
      colonic mucosa using a Ussing-type chamber. Various inhibitors were used to
      investigate the mechanism of action of AEA. The structural change in the membrane
      and the cytotoxicity of AEA in the intestinal mucosa were evaluated by measuring
      the electrical resistance of the membrane (R(m)) and lactate dehydrogenase (LDH)
      activity, respectively. AEA significantly increased the permeation of CF in a
      dose-dependent manner. The enhanced permeability was significantly suppressed by
      a histamine H(1) receptor antagonist, pyrilamine, and a mast cell stabilizer,
      ketotifen, but not by a histamine H(2) receptor antagonist, cimetidine. The
      enhancing effect was also inhibited by an inhibitor of protein kinase C (PKC).
      Potential difference and short-circuit current values decreased, while R(m)
      values remained constant throughout the experiment. The addition of AEA to the
      mucosal solution decreased R(m) to 30%, but then remained constant. LDH activity
      with AEA was not significantly different from that of the control. In conclusion,
      AEA is a candidate for effective absorption enhancers without damage of the
      membrane and cytotoxicity. We propose that AEA stimulates mast cells within the
      colonic mucosa to release histamine, which probably bind to the H(1) receptor.
      The intracellular PKC route activated by H(1) receptor activation enhances the
      permeability of water-soluble and poorly permeable drugs via opening of tight
      junctions in rat colonic membrane.

PMID- 12499650
TI  - Pharmacokinetics of ketotifen fumarate after intravenous, intranasal, oral and
      rectal administration in rabbits.
AB  - The pharmacokinetics of ketotifen fumarate (KF) was examined after administration
      in rabbits through four different routes (intravenous, intranasal, oral and
      rectal). The time-course of the plasma concentration of KF after intravenous
      administration (1 mg/kg dose) fitted a two-compartment open model. KF was rapidly
      absorbed and showed a high plasma concentration within 0.33 h after intranasal
      administration. The absolute bioavailability of KF after intranasal
      administration was 66%. After oral administration at a dose of 1 mg/kg, the
      plasma concentration of KF was below the detection limit of HPLC analysis. Even
      at 5 mg/kg, the value of the area under the plasma concentration-time curve (AUC)
      after oral administration of KF was significantly lower than that after
      intranasal administration of 1 mg/kg. Oral bioavailability was only 8%. The very
      low bioavailability of KF after oral administration might be due to the first
      pass effect in the liver. We also prepared suppositories containing KF (1 mg/kg)
      for rectal administration in rabbits. After rectal administration, KF was rapidly
      absorbed and its bioavailability was 34%. These results indicated that the
      intranasal route appears the most effective for administering KF, and that rectal
      administration may be superior to oral administration in terms of
      bioavailability.

PMID- 12499651
TI  - Cell type-dependent divergence of transactivation by glucocorticoid receptor
      ligand.
AB  - The glucocorticoid receptor regulates gene expression mainly by two mechanisms;
      transactivation and trans-repression. A ligand with strong transrepression and
      weak transactivation activity is predicted to be a beneficial agent with potent
      anti-inflammatory activity and minor adverse effects. Recently, the profile of a
      synthetic steroid, RU24858, has been reported to fulfill this condition in vitro,
      but others have reported no dissociation between the anti-inflammatory activity
      and side effects in vivo. To gain further information on the profile of this
      compound, we evaluated its transactivation ability using a reporter gene analysis
      both in vitro and in vivo. In the in vitro analysis, RU24858 demonstrated only a
      weak transactivation activity in HeLa cells, when compared with prednisolone. In
      CV-1 cells, however, these two glucocorticoids exhibited equivalent
      transactivation activities. This behavior is independent of whether the reporter
      gene is regulated by mouse mammary tumor virus promoter or multiple copies of
      glucocorticoid response element. When the reporter plasmid was inoculated into
      mouse abdominal skin using a gene gun, followed by orally administration of
      glucocorticoids, RU24858 induced significantly higher reporter enzyme activity
      than prednisolone. These results suggest that the profile of RU24858 is divergent
      and its transactivation ability is comparable to prednisolone depending on the
      cell-type both in vitro and in vivo.

PMID- 12499652
TI  - Evaluation of skin barrier function using direct current II: effects of duty
      cycle, waveform, frequency and mode.
AB  - The aim of this study was to evaluate the reduction in skin barrier function
      caused by pulsed iontophoresis by measuring resistance in the short term.
      Experiments under direct current (DC) and pulsed direct current (PDC) conditions
      were carried out using rat abdominal skin in vivo. The resistance was measured
      every 62.5 micros and analyzed using a two-compartment model consisting of
      surface and skin resistance. Moreover, the initial value and the rate constant of
      surface resistance were calculated with the non-linear approximation program.
      Using this method, effects of duty cycle, waveform, frequency and mode on the
      skin barrier function were examined. The barrier function decreased with
      increasing duty cycle. With regard to waveforms, the influence on the skin
      barrier function was greatest in the order of sine, rectangular, saw and
      triangular waveforms. A frequency of less than 100 Hz reduced the barrier
      function. Considering the reduction in barrier function and skin polarization,
      the PDC of a rectangular waveform (around 75% as duty cycle and less than 100 Hz
      as frequency) or sine waveform was most suitable. In addition, the difference in
      the amount of drug delivered by DC and by PDC was discussed.

PMID- 12499653
TI  - Anxiolytic and sedative effects of extracts and essential oil from Citrus
      aurantium L.
AB  - Citrus aurantium L. is commonly used as an alternative treatment for insomnia,
      anxiety and epilepsy. Essential oil from peel (EOP) and hydroethanolic (70% w/v)
      extract (HE) from leaves were obtained. Hexanic (HF), dichloromethanic (DF) and
      final aqueous (AF) fractions were obtained from HE by successive partitions.
      Swiss male mice (35-45 g) were treated orally with 0.5 or 1.0 g/kg of these
      preparations 30 min before the experiments for the evaluation of the
      sedative/hypnotic activity (sleeping time induced by sodium pentobarbital - SPB:
      40 mg/kg, i.p.), anxiolytic activity (elevated plus maze--EPM) and anticonvulsant
      activity (induced by pentylenetetrazole--PTZ: 85 mg/kg, sc or by maximal
      electroshock--MES: 50 mA, 0.11 s, corneal). The results showed that EOP (0.5
      g/kg) increased the latency period of tonic seizures in both convulsing
      experimental models. This effect was not dose-dependent. Treatment with 1.0 g/kg
      increased the sleeping time induced by barbiturates and the time spent in the
      open arms of the EPM. Specific tests indicated that the preparation, in both
      doses used, did not promote deficits in general activity or motor coordination.
      HF and DF fractions (1.0 g/kg) did not interfere in the epileptic seizures, but
      were able to enhance the sleeping time induced by barbiturates. The results
      obtained with EOP in the anxiety model, and with EOP, HF and DF in the sedation
      model, are in accord with the ethnopharmacological use of Citrus aurantium L.,
      which could be useful in primary medical care, after toxicological investigation.

PMID- 12499654
TI  - Serum concentrations of delta 5-3 beta-hydroxysteroids in type 2 diabetes
      mellitus.
AB  - We examined the serum concentrations of delta(5)-3beta-hydroxysteroids,
      pregnenolone (Preg), 17-hydroxypregnenolone (17-OH-Preg), dehydroepiandrosterone
      (DHEA), androstenediol (ADIOL) and their sulfates in 30 well controlled (Group I:
      HbA1c<7.0%) and 15 poorly controlled (Group II: HbA1c>7.1%) type 2 diabetic
      patients, and 30 normal controls. These patients were treated with diet therapy
      or anti-diabetic agent. The distribution of gender and age of the subjects were
      matched between the groups. The serum levels of sulfo-conjugated and unconjugated
      steroids described above were measured by GC-MS and enzyme immunoassay (EIA),
      respectively. The serum levels of the entire sulfo-conjugated steroid measured in
      this study were significantly lower in Groups I and II than in controls. On the
      other hand, Preg levels in both Groups I and II were significantly higher than
      those in controls, whereas the serum levels of the downstream unconjugated
      steroids were not different from controls. To investigate the effect of
      sulfonylurea (SU) on the serum levels of steroids, the serum concentrations of
      steroids between the patients who were treated with diet therapy and SU agent
      were compared in Group I. No significant differences were observed between both
      groups. These results suggest that (1) since increased Preg levels did not cause
      any changes in the downstream delta(5)-3beta-hydroxysteroid levels, the metabolic
      pathway of delta(4)-3-ketosteroids may be accelerated in type 2 diabetes; (2)
      serum steroid levels were not affected by SU treatment; (3) sulfo-conjugated
      steroid catabolism was altered in type 2 diabetes; (4) the decreased sulfo
      conjugated steroids especially ADIOLS may contribute to the alteration of sex
      steroid levels and onset or exacerbate infectious diseases in diabetes.

PMID- 12499655
TI  - Determination of ethanol in biological samples by gas chromatography with an
      electron-capture detection.
AB  - A simple and sensitive procedure for determination of ethanol in biological
      samples was established. In this procedure, ethanol in biological samples was
      first converted to acetaldehyde by yeast alcohol dehydrogenase. Then,
      acetaldehyde formed was derivatized to 2,4-dinitrophenylhydrazone, which was
      determined by gas chromatography with an electron-capture detection. Ethanol
      concentration in 1 ml of rat blood plasma can be measured as 19.5 nmol/ml with
      98.0% recovery. Since this procedure enable to determine minute amount of ethanol
      in biological samples, the method is useful to study the metabolism of ethanol.

PMID- 12499656
TI  - A simple method for the selection of a suitable emulsifier based on color
      difference.
AB  - The purpose of this study was to establish a simple and rapid method for
      selecting a nonionic surfactant to prepare an emulsion that can maintain a stable
      emulsification phase. As an index of the degree of emulsification, the white
      chromaticity of the prepared sample was measured using a color difference meter.
      When liquid paraffin was used as an oil, the color difference (dE(H)) was shown
      as a change in a V-shaped curve depending on changes in the hydrophile-lipophile
      balance (HLB) number of sorbitan ester, polyoxyethylene sorbitan ester, or
      polyethyleneglycol ester. Although there was a difference in the minimal value of
      dE(H) in these experiments, the dE(H) was similar to the required HLB of liquid
      paraffin (HLB=10). On the other hand, no relationship was found between the HLB
      number and color difference when polyglycerol ester was used. It seems that there
      was possibility of the effect by the lowering of apparent HLB with a collapse of
      the hydration. These results indicate that color difference could be utilized for
      the selection of surfactants, except for polyglycerol ester.

PMID- 12499657
TI  - Effect of dried fruits of Carica papaya Linn on hepatotoxicity.
AB  - Ethanol and aqueous extracts of Carica papaya has been evaluated for its anti
      hepatotoxic activity. The ethanol and aqueous extracts of Carica papaya showed
      remarkable hepatoprotective activity against CCl(4) induced hepatotoxicity. The
      activity was evaluated by using biochemical parameters such as serum aspartate
      amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase,
      total bilirubin and gamma glutamate transpeptidase (GGTP). The histopathological
      changes of liver sample was compared with respect to control.

PMID- 12499658
TI  - Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth
      involve activation of NK cells.
AB  - Natural killer (NK) cells are directly cytotoxic for tumor cells and play a
      primary role in regulating immune responses. We monitored levels of NK cell
      cytotoxic activity in cancer patients receiving D-Fraction extracted from maitake
      mushrooms (Grifola frondosa). Elevated levels of cytotoxic activity were
      maintained for one year. To elucidate the mechanisms underlying long-term
      activation of NK cells during treatment with D-Fraction, we examined tumor volume
      and levels of IFN-gamma and TNF-alpha in MM46-bearing C3H/HeN mice to which D
      Fraction was administered for 19 d. D-Fraction markedly suppressed tumor growth,
      corresponding with increases in TNF-alpha and IFN-gamma released from spleen
      cells and a significant increase in TNF-alpha expressed in NK cells. This
      suggests that the D-Fraction activates NK cells even on the 20th day after
      treatment. Furthermore, D-Fraction increased macrophage-derived interleukin (IL)
      12, which serves to activate NK cells. These results suggest that NK cells are
      not only responsible for the early effects of D-Fraction on tumor growth, but
      also for the long-term tumor-suppressive effects of D-Fraction through increased
      IL-12 released from macrophages.

PMID- 12499659
TI  - Inhibitory effect of isoquinoline alkaloids on movement of second-stage larvae of
      Toxocara canis.
AB  - To find new anthelmintics against parasites living in host tissues, we used an in
      vitro assay to screen isoquinoline alkaloids for nematocidal activity on the
      larva of dog roundworm, Toxocara canis. To evaluate the efficacy of anthelmintics
      in vitro, Tsuda et al. previously introduced the concept of Relative Mobility
      (RM) of Toxocara larvae. After improvement of the assay system using image data
      processing, we generated a new index, RM(50), the concentration at which RM=50%.
      However, except for pyrantel, the RM(50) of most existing anthelmintics could not
      be calculated because of low activity. Of the isoquinoline alkaloids tested,
      emetine, sanguinarine, 6-methoxydihydrosanguinarine (6-MS), chelerythrine and
      berberine showed strong nematocidal activities. However, these compounds were
      highly cytotoxic; thus, the prospect of their direct application is low. We then
      tested the cytotoxicity (IC(50)) of other isoquinoline alkaloids in HL60 tissue
      culture cells. We continued our search for new anthelmintics by examining in
      detail the relationship between RM(50) and IC(50). We determined that an ideal
      target compound would exhibit a low RM(50)/IC(50) ratio. Allocryptopine,
      dehydrocorydaline and papaverine were identified as potentially effective
      anthelmintics.

PMID- 12499660
TI  - Effects of conjugated linoleic acid on anaphylaxis and allergic pruritus.
AB  - The effects of conjugated linoleic acid (CLA) against anaphylaxis and allergic
      pruritus were investigated using a in vivo assay. Inhibitory effects of CLA were
      observed on the immediate (type 1) hypersensitivity reaction, with CLA
      significantly suppressing the decrease in blood pressure (BP) and blood flow (BF)
      induced by the hen egg-white lysozyme (HEL)-anaphylactic reaction in ddY mice.
      After oral administration, CLA showed antipruritic activity, with significant
      inhibition of scratching behavior induced by compound 48/80 (COM), a histamine
      release agent. When painted onto the skin, CLA also inhibited COM, platelet
      activating factor, and protease-induced scratching behavior, and COM-induced
      vasodilation of the skin. CLA offers promise as a drug for the treatment of
      allergic and inflammatory pruritus not only as an oral but also a topical agent.
      The present findings demonstrate that CLA can be effective for the prevention and
      treatment of allergic disease with severe pruritus.

PMID- 12499661
TI  - Time- and dose-dependent effect of fosfomycin on suppression of infection-induced
      endotoxin shock in mice.
AB  - Therapeutic effects of fosfomycin (FOF) and imipenem (IPM) were investigated in a
      novel model for endotoxin shock that was caused by intraperitoneal (i.p.)
      infection with 10(8) colony forming units of attenuated Salmonella typhimurium.
      Acute lethal shock was observed in BALB/c and ddY but not in lipopolysaccharide
      (LPS)-nonresponder BALB/lps(d) mice. Effects of FOF, but not its enantiomer, and
      IPM were dose- and time-dependent, since therapeutic efficacy was demonstrated in
      mice injected i.p. or orally at doses of more than 20 mg/kg 15 min before or 1 h
      after infection. Treatment with FOF 1 h postinfection (p.i.) resulted in
      significant decreases in bacterial numbers in spleen and liver, suggesting that
      the antimicrobial activity of FOF seems to closely correlate to suppression of
      infection-induced lethal shock. Regarding coagulation systems, FOF inhibited
      increase in the prothrombin time but upregulated fibrinogen concentration. Plasma
      levels of LPS released from bacilli were significantly higher in FOF- than IPM
      treated mice and infection controls, but both antibiotics showed similar efficacy
      in protection.

PMID- 12499662
TI  - Mechanosensory control of antennal movement by the scapal hair plate in the
      American cockroach.
AB  - The voluntary movement of antennae of blinded cockroaches was examined in the
      tethered-walking condition. An object of metal plate was presented to a tip of a
      single antenna in order to induce tactile orientation behavior. Horizontal
      movements of the antenna before and during the object presentation were analyzed
      both before and after ablation of a mechanosensory organ, the scapal hair plate
      (S-HP), at the base of antenna. The resting antennal position shifted outwardly
      by about 20 degrees after the S-HP ablation. Spontaneous antennal movements in
      ablated animals became stiff and wider ranged. The tactile object was set at two
      different horizontal positions, 45 degrees and 90 degrees clockwise to the head,
      for the right side antenna. The number of contacts in a constant test period was
      significantly decreased in the tests at 45 degrees after ablation. Trajectories
      of antennal movements before and after contacts were categorized into four
      patterns. In the case that an antenna made contact with the object during its
      abduction (outward) movement, it then passed the object outwardly or withdrew
      inwardly. These were termed "outward-pass (O-P)" and "outward-withdrawal (O-W)"
      patterns, respectively. Similarly, contacts during the adduction (inward)
      movement were divided into "inward-pass (I-P)" or "inward-withdrawal (I-W)"
      pattern. Significant effects of the S-HP ablation appeared in the tests at 90
      degrees : the I-P pattern mostly disappeared and was replaced by the I-W pattern.
      The results strongly suggest that the S-HP has crucial roles for controlling both
      spontaneous and stimulated movements of the cockroach antenna.

PMID- 12499663
TI  - Stimulatory effects of prostaglandin E2 on neurogenesis in the dentate gyrus of
      the adult rat.
AB  - Neurogenesis in the dentate gyrus of adult rodents is elicited by transient
      global ischemia. Cyclooxygenase (COX) -2, a rate-limiting enzyme for prostanoid
      synthesis, is also induced by ischemia. We recently found that the administration
      of a non-selective COX inhibitor to ischemic animals suppressed cell
      proliferation in the subgranular zone (SGZ) at the dentate gyrus of the
      hippocampus. To clarify whether prostaglandin E2 (PGE2) synthesis by COX's is
      involved in neurogenesis, sulprostone, an analogue of PGE2, was injected into the
      rat hippocampus. Sulprostone injection increased the number of 5-bromo-2'
      deoxyuridine (BrdU)-positive cells in the SGZ. BrdU-positive cells also expressed
      polysialylated isoforms of neural cell adhesion molecule and neuronal nuclear
      antigen. These results suggest that PGE2 plays an important role in the
      proliferation of cells in the SGZ.

PMID- 12499664
TI  - Innervation of holothurian body wall muscle: inhibitory effects and localization
      of 5-HT.
AB  - We investigated innervation to body wall muscles as well as distribution of 5-HT
      (serotonin) and its effects on longitudinal muscles of body wall (LMBW) of the
      sea cucumber Apostichopus japonicus. With serial sections we found neural
      branches and fibers extending from hyponeural part of radial nerve towards LMBW
      and circular muscles of body wall. With the aqueous aldehyde (Faglu) method
      yellow fluorescence indicating indolamines was observed in LMBW and in the
      mesentery connecting LMBW to the body wall. With indirect immunohistochemistry 5
      HT-like immunoreactivity was observed in LMBW and in mesentery. These results
      strongly suggested that both LMBW and mesentery contained 5-HT. The effects of
      monoamine neurotransmitters were studied in LMBW. Putative neurotransmitters
      tested were 5-HT, adrenaline, noradrenaline, dopamine, and DOPA at the
      concentration of 10(-6) M. The application of 5-HT caused no contraction or
      relaxation, but it inhibited the contraction induced by 10(-6)-10(-5) M
      acetylcholine (ACh). Catecholamines were ineffective by themselves and had no
      effects on the contraction induced by ACh. The present histological,
      histochemical, and pharmacological studies strongly suggested that holothurian
      LMBW was innervated by inhibitory serotonergic neurons of the hyponeural nervous
      system.

PMID- 12499665
TI  - Retinal topography of ganglion cells and putative UV-sensitive cones in two
      Antarctic fishes: Pagothenia borchgrevinki and Trematomus bernacchii
      (Nototheniidae).
AB  - Accessory corner cones (ACC) have recently been suggested to be UV-sensitive
      photoreceptor cells. With a view toward explaining prey detection, we examined
      the topography of retinal ganglion cells and ACCs in two Antarctic nototheniids
      occupying different ecological niches: the cryopelagic Pagothenia borchgrevinki
      and the benthic Trematomus bernacchii. Isodensity maps of retinal ganglion cells
      showed that the main visual axis, coincident with the feeding vector, was in a
      forward direction in both species. Visual acuity was determined as 3.64 and 4.77
      cycles/degree for the respective species. In P. borchgrevinki the highest density
      of ACCs was associated with the eye's main visual axis. This suggested that this
      species uses UV-vision during forward-swims and probably in encounters with prey.
      On the other hand, T. bernacchii possessed two horizontal band-shaped high
      density areas of ACCs, which stretched from temporal to nasal and ventral to
      peripheral retinal regions. Therefore, this species appears to use UV-vision to
      watch prey across the entire circumference of the lateral area and in the water
      column above its head.

PMID- 12499666
TI  - Localization of retinal proteins in the stalk and dorsal eyes of the marine
      gastropod, Onchidium.
AB  - Onchidium possesses stalk eye (SE) and dorsal eye (DE) which comprise part of a
      unique multiple photoreceptive system. The retina of SE consists of rhabdomeric
      type visual cells, whereas the DE contains two types of photoreceptor cells;
      ciliary-type cells in the retina and rhabdomeric-type cells in the lens. High
      performance liquid chromatography (HPLC) analyses revealed the presence of 11-cis
      retinal as well as all-trans-retinal in both eyes. The amount of retinal of one
      DE (0.17 pmol) is far less than that in one SE (0.41 pmol) in the dark-adapted
      Onchidium. In the dark-adapted SE, the amount of all-trans-retinal was higher
      than that of 11-cis-retinal. This finding is consistent with the presence of
      photic vesicles, including retinochrome, in rhabdomeric-type visual cells. In
      contrast, a higher amount of 11-cis-retinal than all-trans-retinal was present in
      dark-adapted DE, although this was decreased in light-adapted DE. Upon UV
      irradiation following treatment with sodium borohydride (NaBH(4)), the
      fluorescence (derived from retinochrome) was observed in the somatic layer of SE.
      Additional fluorescence (due to rhodopsin) was observed in the villous layer upon
      treatment with NaBH(4) after denaturation. However, only weak, obscure
      fluorescence of retinyl proteins was observed in the DE, not in a specific but an
      indefinite area on treatment with NaBH4 with or without denaturation. With
      fluorescence histochemistry, the localization of rhodopsin and retinochrome was
      confirmed at specific regions in the retina of the SE, whereas no distinct
      localization of these photopigments in DE was demonstrated. The amount of retinal
      to detect the fluorescence may be too low in the DE, or photopigments of DE may
      differ in chemical nature from those of SE.

PMID- 12499667
TI  - Female preference for nest size in the stream goby Rhinogobius sp DA.
AB  - Females of the stream goby Rhinogobius sp. DA with paternal care favor males
      courting in fast water currents, whereby they mate males of high parental
      ability. Here we examined female choice of male nest size of this goby in
      laboratory. The dichotomous choice experiment clearly indicated that females
      prefer large nests. Spawning at large nests seems to improve egg survival rates
      in natural habitats in this goby. We discuss the possibility of multiple criteria
      in mate choice of this goby.

PMID- 12499668
TI  - Variability of autogamy-maturation pattern in genetically identical populations
      of Paramecium tetraurelia.
AB  - Autogamy in Paramecium tetraurelia is a form of sexual reproduction in a single
      cell that results in homozygosity in every genetic locus. Autogamy becomes
      inducible by natural starvation several fissions after the previous autogamy, and
      percent autogamy increases gradually with clonal age to reach 100%. We here
      report the degree of variability of the autogamy-maturation pattern, and how it
      is inherited through autogamous generations. We assessed the autogamy-maturation
      pattern by monitoring percent autogamy at the ages of 9, 18 and 27 fissions in
      the wild-type stock 51. To determine how the autogamy-maturation pattern is
      inherited, clones that showed the lowest and the highest percent autogamy at age
      18 in a given autogamous generation (Gn) were examined for their percent autogamy
      in the next autogamous generation (Gn+1). This procedure was repeated through
      successive autogamous generations. We found that percent autogamy at ages 9 and
      27 was rather stable (low and high, respectively), while it was extremely
      variable at age 18 ranging from 3% to 100%. We also found that percent autogamy
      at age 18 in the progeny clones was variable irrespective of percent autogamy at
      age 18 in the parental clones; there was no regular rule such as producing
      progeny with higher (or lower) percent autogamy from parents with lower (or
      higher) percent autogamy.

PMID- 12499669
TI  - Effects of proteasome inhibitor (lactacystin) and cysteine protease inhibitor (E
      64-d) on processes of mitosis in Xenopus embryonic cells.
AB  - At least two different protease pathways have been implicated in the degradation
      that is required to control the eukaryotic cell cycle; these two pathways center
      on the activities of ubiquitin/proteasome and cysteine protease. The proteasome
      inhibitors, lactacystin and AcLLnL and the cysteine protease inhibitor E-64-d
      were tested for their ability to inhibit the cell cycles of Xenopus embryos.
      Lactacystin, AcLLnL and E-64-d all caused the complete arrest of the cell cycle.
      To define the specific cell cycle processes that were affected by the two
      inhibitors, we performed a cytological analysis. Inhibition of the cell cycle by
      lactacystin and E-64-d occurred during prophase and metaphase. The number of
      cells that arrested in prophase was 1.4-times higher in the E-64-d-treated group
      than in the control group and the number of arrested cells in the lactacystin
      treated group was 1.4-times higher than in the E-64-d-treated group. The number
      of cells that arrested in metaphase was 3-to-4-times higher in the E-64-d and
      lactacystin groups than in the control group. These results indicate that both
      cysteine protease(s) and proteasomes are involved in the prophase and metaphase
      stages of cell division.

PMID- 12499670
TI  - Cultivation and characterization of planarian neuronal cells isolated by
      fluorescence activated cell sorting (FACS).
AB  - Studies using molecular markers have revealed that planarians possess a highly
      organized brain. Here we separated brain neurons from dissociated planarian head
      cells by fluorescence activated cell sorting (FACS), and characterized them by
      single cell PCR analysis and cell culture. Dissociated cells were labeled with
      three different fluorescent dyes, Hoechst 33258, Merocyanine 540, and Propidium
      Iodide (PI), and fractioned by FACS. Interestingly, we have succeeded in
      identifying a cell fraction specific to the head, which we have named the head
      abundant cell fraction (HAC). Most of the HAC expressed neuron-specific genes and
      proteins. When they were cultured in vitro, they showed an ability to extend
      neurites on several types of extracellular matrices (ECMs), and, depending on the
      ECM type used, presented a high level of plasticity in morphology and gene
      expression.

PMID- 12499671
TI  - Seasonal changes in the sexualization of the planarian Dugesia ryukyuensis.
AB  - Asexual individuals in a fissiparous clone of the planarian Dugesia ryukyuensis
      develop hermaphroditic sexual organs and eventually undergo sexual reproduction
      instead of asexual reproduction if they are fed with the adults of Bdellocephala
      brunnea, an oviparous planaria. The experimental sexualization means that the
      adults of B. brunnea contain a putative sexualizing substance(s), which is the
      first candidate for the chemical(s) responsible for switching from asexual to
      sexual reproduction in metazoans. In the present study, the feeding experiment
      over two consecutive years revealed that the experimental sexualization has
      seasonal changes. In summer, the asexual individuals were not fully sexualized,
      though they developed a pair of ovaries. The developing ovaries degenerate if the
      feeding is stopped. On the contrary, in winter, they developed all the sexual
      organs. The sexual organs keep developing even if the feeding is stopped after a
      certain critical point named the point-of-no-return. It was demonstrated that the
      extreme difference of the sexualization was attributed to the seasonal change of
      the quality and/or quantity of the sexualizing substance contained in B. brunnea,
      as well as the minor change of the susceptibility to the sexualizing substance in
      the asexual individuals. On the other hand, the histological research of B.
      brunnea revealed that the degree of the maturation of the sexual organs varied
      extremely through a year. Taking these results into account, we suggest that the
      production of the sexualizing substance has no direct relation to any particular
      mature sexual organs.

PMID- 12499672
TI  - A new cheilostome bryozoan with gigantic zooids from the North-West Pacific.
AB  - Gontarella gigantea gen. et sp. nov. is described from two stations, one in the
      Sea of Okhotsk and the second on the Pacific side of the Small Kuril Arc. This
      membraniporiform anascan cheilostome bryozoan has very large zooids, the largest
      known among extant sheet-like encrusting anascans. Comparative data on similar
      sheet-like cheilostomes gathered from the literature shows that the new species
      represents a conspicuous outlier in size, with the surface area of the zooid
      being approximately twice that of the next largest species. Skeletal evidence,
      including the lack of ovicells, indicates that G. gigantea belongs within the
      malacostegan family Electridae. The gigantic ancestrula suggests that the species
      has a cyphonautes larva about 1 mm in maximum dimension.

PMID- 12499673
TI  - Speciation and dispersal of Tribolodon species (Pisces, Cyprinidae) around the
      Sea of Japan.
AB  - Gene products of 22 protein coding loci from 29 populations of a uniquely sea
      going cyprinid genus Tribolodon, T. hakonensis (anadromous and/or river
      resident), T. brandtii (anadromous), T. ezoe (freshwater) and T. nakamurai
      (freshwater), were analyzed in order to infer the genetic divergence and
      dispersal of Tribolodon species around the Sea of Japan. According to the genetic
      distance, T. brandtii is located near the center between T. hakonensis and T.
      ezoe-T. nakamurai cluster. The outgroup root (Pseudaspius leptocephalus,
      Rhynchocypris lagowskii and Leuciscus waleckii) is attached between T. hakonensis
      T. brandtii and the T. ezoe-T. nakamurai clusters. The origin of the genus
      Tribolodon and its salinity tolerance may date back to the Miocene Sea-of-Japan
      Lake and the Pliocene Paleo-Sea-of-Japan, respectively, as judged from the
      divergence time between Tribolodon and the outgroups. The genetic relationships
      and distribution pattern of Tribolodon species suggest they speciated on the
      Sakhalin-Japan side, and the continental populations of T. hakonensis and T.
      brandtii originated from anadromous colonizers. A new faunal element of Japanese
      freshwater fishes, the Sakhalin-Japan sub-element, is proposed for Tribolodon and
      some other fishes.

PMID- 12499674
TI  - Phylogenetic relationships of the Asian box turtles of the genus Cuora sensu lato
      (Reptilia: Bataguridae) inferred from mitochondrial DNA sequences.
AB  - Phylogenetic relationships of the genus Cuora sensu lato (Cuora sensu stricto and
      Cistoclemmys) and other testudinoid genera were inferred from variations in 882
      base positions of mitochondrial 12S and 16S rRNA genes. Results yielded a robust
      support to the monophyly of a group (Cuora group) consisting of Cuora sensu lato
      and the monotypic Pyxidea. Within the Cuora group, the continental Cuora (sensu
      stricto) and the two subspecies of Ci. flavomarginata constituted two well
      supported monophyletic groups. Distinctly small interspecific genetic distances
      in the former groups suggested that in the continent speciations in Cuora took
      place much later than the primary divergences in the Cuora group, or speciations
      in other related genera, such as Mauremys. Our analyses failed to provide a
      substantial support to the monophyly of any other combinations of taxa within the
      Cuora group, including Cuora in broad and strict senses, and Cistoclemmys as
      consisting of Ci. galbinifrons and Ci. flavomarginata. Besides these, our results
      also suggested the non-monophyly for the Batagurinae and the Geoemydinae, and
      sister relationships of the Bataguridae with Testudinidae rather than with the
      Emydidae.

PMID- 12499675
TI  - A genetic method to distinguish crossbred Inobuta from Japanese wild boars.
AB  - To distinguish pig-wild boar crossbred Inobuta from Japanese wild boar
      populations, a genetic method by using mitochondrial DNA (mtDNA) haplotypes and
      the nuclear glucosephosphate isomerase-processed pseudogene (GPIP) was developed.
      Sixteen mtDNA haplotypes from 152 wild boars from Kyushu, Shikoku and Honshu
      islands of Japan were distinct from those from Asian and European domestic pigs.
      Five alleles of GPIP were classified into two groups: 1). alleles GPIP*1, GPIP*3
      and GPIP*3a from Japanese wild boars, Asian wild boars and domestic pigs; 2).
      alleles GPIP*4 and GPIP*4a from European wild boars and domestic pigs. An
      extensive genetic survey was done to distinguish the crossbred Inobuta from 60
      wild boars hunted on Tsushima Island, Goto Islands, and Nagasaki and Ooita
      Prefectures. The mtDNA haplotypes from the 60 samples showed Japanese wild boars,
      but four wild boar samples from Nagasaki Prefecture had the European GPIP allele,
      GPIP*4. These results showed that nuclear DNA polymorphism analysis is useful, in
      addition to mtDNA haplotype assay, to detect "Inobuta" having the European
      genotype from Japanese wild boar populations.

PMID- 12499676
TI  - Molecular phylogeny among local populations of weaver ant Oecophylla smaragdina.
AB  - The molecular phylogeny of 24 Oecophylla smaragdina populations and two O.
      longinoda populations was studied using 647 bp of the mitochondrial cyt b gene.
      The phylogenetic analysis suggested that O. smaragdina and O. longinoda were
      separated from each other first, and after that the first within-species
      divergence of O. smaragdina occurred in early stage of their history, in which
      the Asian, Australian, and Sulawesian groups rose. This grouping was almost
      coincident with the distribution of landmass in glacial periods in Pleistocene.
      Thereafter, each group seemed to have independently diverged into present
      populations on each landmass.

PMID- 12499677
TI  - Variation in mitochondrial DNA of Vietnamese pigs: relationships with Asian
      domestic pigs and Ryukyu wild boars.
AB  - Mitochondrial DNA (mtDNA) sequences (574 bp) of 30 Vietnamese pigs (large and
      small) were examined and compared with those of 61 haplotypes from wild boars and
      domestic pigs from various locations in Asia. The large Vietnamese pigs had
      genetic links to Ryukyu wild boars in southern Japan. The small Vietnamese pigs
      were closely related to other East Asian domestic pigs. These results indicate
      that Vietnamese pigs are genetically diverse and may be descendents of wild and
      domestic pigs from other regions of Asia.

PMID- 12499678
TI  - Leader-body junction sequence of the viral subgenomic mRNAs of porcine
      reproductive and respiratory syndrome virus isolated in Taiwan.
AB  - In combination of utilizing a leader specific primer and primers complementary to
      porcine reproductive and respiratory syndrome virus (PRRSV) genome through RT
      PCR, the leader junction sequences of subgenomic mRNA (sg mRNA) was identified
      from a Taiwanese isolate of PRRSV. Thirty-six cDNA clones derived from sg mRNAs
      2, 3, 4, 5, 6 and 7 were determined. The junction sequences analyzed from
      different sg mRNA were found to contain a similar 5 nucleotide sequence motif,
      (U/G)(C/A)(A/G)CC. The distance between the junction site and the translation
      initiation codon of the down stream open reading frame varied from 4 to 226
      nucleotides. Minor heterogenecity was observed in the nucleotide sequence
      surrounding the junctions from all six sg mRNA analyzed. However, for sg mRNA 7,
      two junction sites approximately 103 nucleotides apart from each other were
      identified. The additional site is a new junction not previously reported in sg
      mRNA 7 from other PRRSV strains.

PMID- 12499679
TI  - Vascular endothelial growth factor (VEGF) promotes the early development of
      bovine embryo in the presence of cumulus cells.
AB  - Three experiments were conducted to determine the effect of Vascular Endothelial
      Growth Factor (VEGF) on bovine embryonic development in vitro. Human recombinant
      VEGF(165) was employed at 5 ng/ml in modified synthetic oviduct fluid. In Exp. 1,
      bovine cumulus oocyte complexes were matured with or without VEGF for 22 hr,
      inseminated without VEGF for 6 hr, then cultured with or without VEGF for 42 hr.
      The cleavage rate and the development rate to 4- to 8-cell were higher (P<0.05)
      in groups with VEGF during in vitro maturation (IVM, 71.4% and 59.6%), in vitro
      culture (IVC, 70.3% and 62.3%), and both IVM and IVC (75.9% and 67.8%) than in
      the group cultured thoroughly without VEGF (49.9% and 38.4%, respectively). In
      Exp. 2, 4- to 8-cell embryos produced in vitro without VEGF were removed from
      cumulus cells at 48 hr post-insemination (Pi) and cultured with or without VEGF
      for 144 hr. The development rates to blastocyst at 96 hr (D6), 120 hr (D7) and
      144 hr (D8) were similar (P>0.05) in both groups. In Exp. 3, cumulus cells were
      removed from presumptive embryos produced by IVM and IVF without VEGF at 10 hr
      Pi. Denuded embryos were cultured with or without VEGF for 38 hr or 182 hr. The
      cleavage rate and the development rates to 4- to 8-cell at 48 hr Pi and to
      blastocyst on D6, D7 and D8 were similar (P>0.05) in all groups. These results
      suggest that VEGF has a beneficial effect on the initial development of bovine
      embryo through surrounding cumulus cells.

PMID- 12499680
TI  - Detection of the anti-P53 antibodies in dogs with tumors.
AB  - To detect the anti-P53 antibodies of dogs with tumors, a GST-recombinant canine
      (rc) P53 fusion protein was expressed and purified. Immunoblot analysis was
      performed using this GST-rcP53 fusion protein as an antigen and serum samples
      from dogs suffering from tumors as primary antibodies. Out of 16 serum samples
      obtained from various tumor cases, four samples showed reaction with GST-rcP53.
      In contrast, serum from other 12 dogs with tumors, four dogs with non-neoplastic
      diseases and two control healthy dogs (as controls) did not show any reaction
      with GST-rcP53 in immunoblotting. The p53 gene mutation and the P53 protein
      expression were examined, using the tumor tissues to explore the relationship
      between the existence of the GST-rcP53 bands, gene mutations of p53 and the
      accumulation of P53 protein. One case, which showed a clear GST-rcP53 band, had a
      point mutation of the p53 cDNA and showed nuclear accumulation of P53 protein.
      These results suggest that the anti-P53 antibodies are also produced in tumor
      dogs with p53 gene mutations.

PMID- 12499681
TI  - Comparison of the cardiovascular effects of intracellular cyclic adenosine 3',5'
      monophosphate (cAMP)-modulating agents in isoflurane-anesthetized cats.
AB  - The inotropic, chronotropic, and vasodilatory effects of five commonly used
      cyclic adenosine 3',5'-monophosphate (cAMP)-modulating agents were evaluated.
      Hemodynamic functions were measured continuously in isoflurane-anesthetized cats
      during infusion of the following: dobutamine (DOB; 2.5, 5 and 10 microg/kg/min;
      n=8), dopamine (DOP; 1.25, 2.5, 5 and 10 microg/kg/min; n=5), milrinone (MIL;
      2.5, 5 and 10 microg/kg/min; n=8), 6-(3-dimethyl-aminopropionyl) forskolin
      hydrochloride (COL; 0.2, 0.4, 0.8, and 1.6 microg/kg/min; n=7), and bucladesine
      sodium (BUC; 10, 20, and 40 microg/kg/min; n=9). At the highest infusion rate,
      DOB and DOP produced the greatest positive inotropic (increase in left
      ventricular (LV) dP/dt = 89 +/- 4% and 75 +/- 6%, respectively) and chronotropic
      (increase in heart rate (HR) = 42 +/- 4% and 22 +/- 6%, respectively) effects.
      MIL and COL produced similar albeit less pronounced positive inotropic (increase
      in LV dP/dt = 18 +/- 3% and 22 +/- 6%, respectively) and chronotropic (increase
      in HR = 13 +/- 4% and 21 +/- 4%, respectively) effects. Both also had significant
      vasodilatory effects (decrease in peripheral resistance (PR) = -30 +/- 2% and -35
      +/- 7%, respectively). In contrast, BUC produced only vasodilatation (decrease in
      PR = -33 +/- 6%). Hence, MIL, COL, and BUC had significant vasodilatory effects
      and less-pronounced inotropic effects than the catecholamines DOB and DOP. The
      vasodilatory effects of non-catecholamine drugs for treatment of congestive heart
      failure should translate into beneficial decreases in both pre-load and after
      load. In contrast, the strong inotropic effects of DOB and DOP should be
      beneficial in the treatment of acute heart failure and anesthetic crisis.

PMID- 12499683
TI  - Fenprostalene-induced abortion in bitches.
AB  - A long-acting prostaglandin F(2alpha) analogue, fenprostalene, was subcutaneously
      administered singly at doses of 5, 10, 25, 50, 100 or 150 microg on day 25 after
      ovulation during pregnancy in bitches (n=4 for each dosage), and maintenance of
      pregnancy, changes in plasma progesterone concentration, interval between the
      treatment and subsequent estrus and conception rate at that estrus were studied.
      Abortion was associated with a decrease in the plasma progesterone concentration
      below about 2 ng/ml, and the abortifacient effect was dose-dependent.
      Administration of 50 microg or more of fenprostalene induced abortion in all dogs
      3 to 13 days after the treatment. The interval between administration and
      subsequent estrus was markedly shorter in the aborted bitches than in the non
      aborted ones (P<0.01). The conception rate at the estrus in the aborted dogs was
      50%, whereas all of the bitches who had not aborted became pregnant. The results
      indicate that a single administration of fenprostalene could induce abortion
      during mid-pregnancy in bitches, and the subsequent estrus may come early with a
      low conception rate.

PMID- 12499684
TI  - Evaluation of the field application of PCR in the eradication of contagious
      equine metritis from Japan.
AB  - The effectiveness of the polymerase chain reaction (PCR) as a field application
      test for the eradication of contagious equine metritis (CEM) was evaluated. Seven
      thousands five-hundred and thirty-four genital swabs were collected from 4,026
      Thoroughbred broodmares and stallions in Japan to test "high risk" horses as well
      as for general surveillance testing from 1998 to 2001. Bacterial isolation as
      well as PCR testing of original specimens and cultured specimens was performed
      for detection of Taylorella equigenitalis from genital swabs. As a result, T.
      equigenitalis was detected in 12 mares and 1 stallion by PCR, although the
      bacteria were isolated from only 2 of the PCR-positive mares. CEM-infected and
      carrier horses were treated by a combination of chemotherapy and surgery.
      Subsequent follow-up testing over a 3-year period did not detect T.
      equigenitalis. It was demonstrated that PCR testing was more sensitive than
      isolation as a method for the detection of T. equigenitalis from genital swabs of
      horses in the field. It was therefore suggested that a combination of PCR testing
      and treatment were useful measures in the eradication of CEM from Japan.

PMID- 12499687
TI  - Post-exposure treatment of cats with mouse-cat chimeric antibodies against feline
      herpesvirus type 1 and feline calicivirus.
AB  - In order to confirm the in vivo effectiveness of anti- feline herpesvirus type 1
      (FHV-1) mouse-cat chimeric antibody (FJH2), and anti-feline calicivirus (FCV)
      mouse-cat chimeric antibody (F1D7), cats that had been experimentally infected
      with FHV-1 or FCV were administered intravenously with the chimeric antibodies,
      and observed for clinical manifestations. The symptoms due to FHV-1 or FCV
      infection in the cats administered FJH2 or F1D7 were obviously decreased when
      compared with those of the non-administered control cats. From these results, it
      was confirmed that both FJH2 and F1D7 were effective at reducing the appearance
      of symptoms due to FHV-1 and FCV infection, respectively.

PMID- 12499682
TI  - Production of conjugated linoleic acid by intestinal bacteria in dogs and cats.
AB  - Production of conjugated linoleic acid (CLA) by the intestinal bacteria of dogs
      and cats was demonstrated by incubating their feces with linoleic acid (LA). CLA
      accumulated once, and then decreased with time. The numbers of LA-hydrogenating
      bacteria in the intestines appeared to decrease greatly with the ages of dogs and
      cats. As a major product of LA biohydrogenation, trans-vaccenic acid (t-VA) was
      identified. Most CLA and t-VA were readily solubilized by shaking the incubation
      mixture with bovine serum albumin, which strongly supports the presumption that
      CLA and t-VA are mostly formed on the outer surface of cell membrane, or excreted
      to the outer cell surface. This result suggests that CLA and t-VA can readily be
      absorbed through the large intestines. Triacylglycerol and phospholipid were
      shown to be hydrolyzed to free fatty acids by fecal bacteria, which is critical
      for biohydrogenation to occur, because esterified LA is not hydrogenated.
      However, since the ability of intestinal bacteria to produce CLA is probably low,
      it is desirable to augment CLA production.

PMID- 12499685
TI  - Use of every ten-day criteria for metabolic profile test after calving and dry
      off in dairy herds.
AB  - The traditional metabolic profile test cannot be applied to peripartum dairy
      cows, because these cows are in a state of physiological abnormality making it
      difficult to interpret their blood components. This study aimed at establishing
      and evaluating the practicability of interpreting a metabolic profile test every
      10 days (Ten-day criteria) during the dry and lactation periods in herds with
      high and no incidence of peripartum diseases. Data from 29,043 cows in 1,130
      commercial dairy herds were used to establish standard values every 10 days, mean
      +/- 1.0 standard deviation for the metabolic profile test. The practicability of
      these criteria was evaluated in herds with peripartum diseases. In the ten-day
      criteria, the body condition score, albumin, blood urea nitrogen, glucose, total
      cholesterol, nonesterified fatty acids, gamma-glutamyl transpeptidase and
      aspartate aminotransferase, fluctuated during the dry and early lactation periods
      and there were very big changes in packed cell volume, blood urea nitrogen, total
      cholesterol and magnesium just after calving. The ten-day criteria were able to
      detect overconditioned cows, low levels of albumin, total cholesterol and
      magnesium, and high nonesterified fatty acids in herds with a high incidence of
      peripartum diseases. In conclusion, the ten-day criteria can be successfully
      applied to peripartum cows, and is recommended because it is able to detect
      metabolic abnormalities not only in the herd, but also in individual cows.

PMID- 12499686
TI  - Isolation and serological survey of Salmonella in pigs in Japan.
AB  - A total of 267 fecal and serum samples collected from individual pigs reared on a
      Salmonella-positive farm were subjected to bacteriological and serological
      examinations of Salmonella. Salmonella was isolated from 47 pigs (17.6%) and
      prevalence of antibody to lipopolysaccharide (LPS) of S. Typhimurium, which was
      partly common to S. O4, 12: d: -, was observed in 90 pigs (33.7%). Salmonella was
      isolated from 26 (28.9%) of 90 antibody-positive pigs and 21 (11.9%) of 177
      antibody-negative pigs. Twenty-one of 36 pigs (58.3%) positive for S. O4, 12: d: 
      , five of 10 pigs (50.0%) positive for S. Havana, and none for S. Anatum had
      antibodies. Thus, seropositive rates were higher than isolation-positive rates,
      and antibody prevalence was associated with serovars of the isolates. Then, we
      analyzed antibody prevalence among pigs on Japanese pig farms. The antibodies to
      LPS of S. Typhimurium were found in 195 of 1,498 pigs (13.0%) and in at least one
      serum sample on 35 of 52 farms (67.3%). Our results indicate that Salmonella does
      not seem to be so prevalent in pigs though it is widely prevalent among pig
      farms.

PMID- 12499688
TI  - Heart rate modulation by sympathetic nerves in dogs with heart failure.
AB  - To clarify heart rate modulation by the sympathetic nervous system, dogs with
      naturally acquired and experimentally induced heart failure were examined. Heart
      rate and plasma catecholamine concentrations were measured in clinically healthy
      dogs (control dogs) and dogs with mitral regurgitation (MR) during a resting
      period, a standing period, a period of standing in a medical examination room (to
      which the dogs were unaccustomed), a running period, and a period of recovery
      after running. The heart rate and plasma catecholamine concentration increased in
      control dogs during the standing period and the medical examination room period,
      relative to the resting period. However, dogs with MR did not exhibit any clear
      increase in heart rate or catecholamine concentration under these light stress
      conditions. Running stress increased plasma catecholamine levels in control dogs;
      however, dogs with MR did not exhibit any significant changes. Thirty-two dogs
      with naturally acquired heart disease were classified as grades I to III on the
      ISACHC scale. The degree of increase in heart rate and plasma catecholamine
      levels in dogs with naturally acquired heart failure depended on their degree of
      heart failure. In conclusion, an increased heart rate and an activated
      sympathetic nervous system were observed, even in mild heart failure. This
      chronically activated sympathetic activity is expected to increase myocardial
      oxygen consumption, myocardial hypertrophy, and fibrosis, and to portend a poorer
      prognosis in heart failure.

PMID- 12499689
TI  - Enhanced protection against the migratory phase, but defective protection against
      the intestinal phase of Strongyloides venezuelensis infection in cotton rats,
      Sigmodon hispidus.
AB  - The protective capacity of the cotton rat, Sigmodon hispidus, against the
      migratory and intestinal phases of Strongyloides venezuelensis infection was
      examined. After subcutaneous infection with infective larvae (L(3)), adult worm
      recovery rates from male and female animals on Day 71 were only 0.10% and 0.06%
      of initial dose, respectively. To determine whether this enhanced protection was
      expressed during the migratory phase or the intestinal phase, larval recovery
      from the lungs of cotton rat was evaluated 3 days after subcutaneous L(3)
      infection. The larval recovery rate was only 0.5% of initial dose and about 40
      fold lower than that from control mice. Protection in the intestine was also
      evaluated after intraduodenal implantation of adult worms. About 30% of implanted
      worms became established and worm burden remained constant until Day 28. Despite
      a high worm burden on Day 28, EPG was about 25-fold lower than the peak count. To
      evaluate expulsive capacity and monitor the cellular responses in the intestine
      of cotton rats, adult Nippostrongylus brasiliensis worms were implanted in
      addition to S. venezuelensis. Cotton rats were unable to expel adult S.
      venezuelensis worms, even after 21 days of observation. Although the number of
      mucosal mast cells increased significantly, the intraepithelial migration of mast
      cells was not observed. In contrast, N. brasiliensis was expelled by Day 6 in
      association with goblet cell hyperplasia. These results suggest that in cotton
      rats, the defective intestinal protection against adult S. venezuelensis worms
      results from dysfunction of mucosal mast cells.

PMID- 12499690
TI  - Residues of aflatoxins in the liver, muscle and eggs of domestic fowls.
AB  - The residue of aflatoxins in the liver, muscle and eggs of laying ducks, hens and
      quails and in broiler chickens was examined by conducting 7-day feeding
      experiments with a diet containing 3 ppm Aflatoxin B1 (AFB1). Birds were
      sacrificed on the 8th or 11th day of AFB1 feeding. AFB1 and its metabolites in
      the tissues and eggs were determined by HPLC. The tissue levels of AFB1 and its
      metabolites were higher in quail than in the other birds. The levels of AFB1 and
      its metabolites, including acid-hydrolyzable metabolites, were more than 10-fold
      higher in the liver than in the muscle in all the species. The ratio of AFB1 in
      the feed to the residual level in the liver was 383 in quail, but was > or = 5769
      in the other birds. The corresponding ratios in the egg yolk and albumen of AFB1
      were 4615 and 3846, respectively, in chicken hens, and these values were higher
      than those in the other birds.

PMID- 12499691
TI  - Isolation and characterization of Shiga toxin-producing Escherichia coli O157:H7
      from beef, pork and cattle fecal samples in Changchun, China.
AB  - Meat samples and fecal specimens from adult cattle were collected in Changchun,
      China and were examined for presence of Shiga toxin-producing Escherichia coli
      (STEC) serogroup O157. STEC O157 strains were isolated from 2 (5%) of 40 beef, 1
      (3.3%) of 30 pork, and 3 (1.7%) of 176 adult cattle fecal samples. The strains
      belonged to phage types (PT) 4, 8, or 47. Two beef strains and a strain
      previously isolated from a patient in Shandong, China, were PT-4 and showed a
      similar PFGE pattern, suggesting the possibility of food-borne transmission. It
      is suggested that cattle are a reservoir of STEC O157:H7 and meat products are
      contaminated by this pathogen in Changchun, China as well as in other countries.

PMID- 12499692
TI  - Immunohistochemical localization of transforming growth factor alpha in
      regenerating rat liver.
AB  - Immunohistochemical localization of TGF-alpha and cell proliferation kinetics
      during liver regeneration after two-thirds partial hepatectomy (PH) were
      investigated. Twenty-four to 72 hr after PH, appreciable increase in the number
      of TGF-alpha-positive hepatocytes was observed in zones 1 and 2. At the peak at
      36 hr, almost all positive cells were stained in their nuclei. Considerable
      increase in the BrdU labeling index was observed 24-36 hr after PH with a peak at
      24 hr in zones 1 and 2. These results indicated an association between TGF-alpha
      expression and hepatocyte regeneration. It is suggested that immunohistochemical
      localization of TGF-alpha may be a useful marker of cell proliferation activity
      in rat liver.

PMID- 12499693
TI  - Isolation of myxoviruses from migratory waterfowls in San-in district, western
      Japan in winters of 1997-2000.
AB  - Between November 1997 and February 2000, winter migratory waterfowls of several
      species staying in San-in district, western Japan were surveyed for influenza A
      virus and paramyxovirus at four stations. A total of 18 influenza A viruses was
      isolated from 1,404 fecal samples of whistling swans, pintails, mallards, and
      white-fronted geese. Five different hemagglutinins and eight neuraminidases were
      identified in the viruses isolated, in 11 different combinations, including H7N8
      related to a subtype of a highly pathogenic chicken virus. In 2000, five
      lentogenic (non-pathogenic) Newcastle disease viruses were also isolated from
      white-fronted geese. These results suggested that possible precursor viruses for
      highly pathogenic avian myxoviruses are still brought into Japan by migratory
      waterfowls. The results also support the contention that continued surveillance
      of wild waterfowl population should be an integral part of control policies for
      these serious poultry diseases.

PMID- 12499694
TI  - Serum leptin levels during the periparturient period in cows.
AB  - Serum leptin concentrations were measured in antenatal and postnatal cows housed
      at two different locations. The mean serum leptin concentration was 9.2 +/- 0.6
      ng/m l (n=22) in one group, and was slightly lower in the other (7.4 +/- 0.4
      ng/ml, n=54), probably because of the different nutritional conditions between
      the two groups. There was no consistent variation in relation to the menstrual
      cycle and the periparturient period in both groups. Moreover, serum leptin
      concentrations during the periparturient period were independent of the number of
      delivery and the incidence of mastitis and milk fever. These results are quite
      different from those in rodents and human, suggesting the different regulatory
      mechanism of circulating leptin concentration in cows.

PMID- 12499695
TI  - Lone atrial fibrillation in a dog.
AB  - An intact male Pointer aged 9 year was found to have atrial fibrillation (AF).
      Thoracic radiography and echocardiography as well as routine blood work revealed
      no cardiac disease. Thus, the dog was diagnosed as lone AF. The arrhythmia
      disappeared 6 hr after the initiation of the supportive therapy, and relapse was
      not observed.

PMID- 12499696
TI  - Immunostimulating and growth-promoting effects of sugar cane extract (SCE) in
      chickens.
AB  - Polymorphonuclear cells of the peripheral blood in the chicken significantly
      increased their phagocytosis when cultured with sugar cane extract (SCE; 250
      1,000 microg/ml) for 24 hr. Chickens orally administered SCE (500 mg/kg/day) for
      3 or 6 consecutive days at 1 week of age showed significantly higher body weight
      and gain in body weight/day and a lower food conversion ratio within the growing
      period of 6 weeks than physiological saline-administered control chickens.
      Furthermore, oral administration of SCE also resulted in significantly higher
      immune responses against sheep red blood cells and Brucella abortus. These
      results suggest that SCE has immunostimulating and growth promoting effects in
      chickens.

PMID- 12499697
TI  - Changes in hepatic enzyme activities in transgenic mice carrying human prototype
      c-Ha-ras gene treated with diethylnitrosamine.
AB  - Activities of malate dehydrogenase (MDH) and aspartate aminotransferase in the
      malate-aspartate shuttle were significantly increased in the cytosolic fractions
      of livers with early neoplastic symptoms such as swelling and discoloration in
      transgenic mice carrying the prototype human c-Ha-ras gene, Tg-rasH2 mice, which
      were administered with diethylnitrosamine (DEN) as a carcinogenic chemical at a
      dose of 200 mg/kg body weight. Cytosolic MDH/LDH (lactate dehydrogenase) (ML)
      ratio increased significantly and was considered to be a useful marker to
      characterize the energy metabolism at early neoplastic stage in livers of the Tg
      rasH2 mice.

PMID- 12499698
TI  - Oral allergy syndrome induced by tomato in a dog with Japanese cedar (Cryptomeria
      japonica) pollinosis.
AB  - A dog with Japanese cedar (Cryptomeria japonica, CJ) pollinosis had oral allergy
      syndrome (OAS) after ingesting fresh tomato. The dog showed specific IgE to both
      CJ and tomato allergens. As a negative control, twenty dogs without atopic
      dermatitis that had no exposure to tomato and no specific IgE to CJ allergen were
      used. They had no specific IgE to tomato allergen. Furthermore, IgE cross
      reactivity was observed between CJ and tomato allergens in the dog. We found that
      OAS induced by tomato exists in the dog and there is a relationship between CJ
      and tomato allergens.

PMID- 12499699
TI  - Prevalence and characteristics of intimin- and Shiga toxin-producing Escherichia
      coli from gulls, pigeons and broilers in Finland.
AB  - The role of birds as sources of Shiga toxin-and intimin-producing Escherichia
      coli was studied. Fecal samples from live gulls (n=86), pigeons (n=33) and
      broiler chickens (n=199) from 23 flocks were analyzed for stx and eae by PCR. No
      stx positive samples were detected. In contrast, eae E. coli were highly
      prevalent among gulls (40%), and was also found in pigeons (7%) and chickens (57%
      of the flocks contaminated). The eae positive isolates were analyzed genetically
      and O-serogrouped. One isolate from a pigeon was found to have stx (2f). The
      isolates of gulls differed from those of pigeons and chickens, and all eae E.
      coli isolates from birds differed from human pathogenic strains by the lack of
      EHEC-hlyA and bfp/EAF as well as distribution of O-serogroups. Thus, birds cannot
      be regarded as important carriers of zoonotic stx or eae E. coli in Finland.

PMID- 12499701
TI  - Incidence of Salmonella infection in healthy dogs in Gifu Prefecture, Japan.
AB  - A total of 1,013 feces samples and 8 mesenteric lymphonodus samples obtained from
      apparently healthy dogs were examined for the incidence of salmonella infection.
      One strain of S. typhimurium (ST) was isolated from feces of one dog, and S.
      enteritidis (SE) was isolated from the mesenteric lymphonodus of one dog. Sera
      obtained from 330 apparently healthy dogs were examined for Salmonella antibodies
      using an ELISA with heated whole cells of SE and ST. Fifty-one of the 330 serum
      samples were considered to be positive for salmonella antibodies, including 12
      which were SE-positive and 39 which were ST-positive. These results indicate that
      dogs cause possible environmental problems as Salmonella carriers.

PMID- 12499700
TI  - Seasonal changes of blood composition in captive bottlenose dolphins.
AB  - To determine how blood values in bottlenose dolphins changed during the year, 504
      blood samples were taken from 9 dolphins from 1991 to 1999 and clinical blood
      examinations were undertaken monthly including 3 hematological and 19 serum
      chemistry tests. In creatinine, significant seasonal changes were found among
      three groups of adult males, adult females and juveniles, and the average values
      in summer were 15-38% higher than those in winter. In two out of three groups the
      average total cholesterol value were highest in winter, and the lowest of all
      groups were in summer. In two other groups the peaks of average FFA value were
      recorded in summer, and the lows were in winter.

PMID- 12499702
TI  - Sequence analysis of the NRAMP1 genes from different bovine and buffalo breeds.
AB  - The natural resistance associated macrophage protein 1 (Nramp1) has been reported
      to confer resistance or susceptibility to Mycobacterium bovis, Salmonella
      typhimurium, and Leishmania donovani in the mouse, Mus musculus. A Gly and Asp
      substitution at position 169 of the mouse Nramp protein is invariably associated
      with the resistant and susceptible phenotypes, respectively. The present study
      aimed to detect polymorphisms in the NRAMP1 gene from different cattle and
      buffalo breeds. Genomic DNAs from five breeds of cattle and four breeds of
      buffalo were used in the study. Sequencing showed two nucleotide substitutions
      found in intron 4, three in exon V, and ten in intron 5. An amino acid
      substitution was observed at nucleotide position 1202 in exon V of the Japanese
      black, Angus, Philippine and Bangladesh swamp-type buffaloes which coded for Thr,
      while the Korean cattle, Holstein, African N'dama, Indonesian swamp-type buffalo
      and the Bangladesh river-type buffalo had Ile. All the breeds of cattle and
      buffaloes tested in this study coded for Gly at the position in exon VI which
      corresponds to the same amino acid of the murine Nramp1-resistant phenotype at
      position 169. The phylogenetic relationship among the different breeds showed a
      cluster comprised mainly of cattle and another one mainly of buffaloes.

PMID- 12499704
TI  - Association between atrial septal aneurysm and patent foramen ovale in young
      patients with recent stroke and normal carotid arteries.
AB  - BACKGROUND: Atrial septal aneurysm (ASA) has been considered a potential source
      of cardiogenic embolism for many years. The ASA Multicenter Italian (ASA-MI)
      Study evaluated the prevalence and characteristics of ASA in patients with stroke
      and normal carotid arteries compared with control patients without stroke. The
      purpose of the present study was to evaluate the frequency of ASA and the
      association with patent foramen ovale (PFO) in the subgroup of younger patients
      (aged less than 55 years) included in the ASA-MI Study. METHODS: The ASA-MI Study
      included 606 patients, enrolled between November 1990 and December 1996: 245
      patients with a previous cerebral embolic attack and normal carotid study and a
      control group of 316 patients. They all underwent transthoracic and
      transesophageal echocardiography. The subgroup of younger patients aged less than
      55 years included 90 patients (61 men and 29 women of mean age 49 +/- 5 years)
      (group AY). This group was evaluated and compared with an age- and sex-matched
      control population (61 men; of mean age 48 +/- 6 years) (group BY). RESULTS: The
      prevalence of ASA was 48.8% (95% confidence interval 40-61) in group AY and 22.2%
      in the group BY (95% confidence interval 18-33) (chi(2) = 5.968; p = 0.01).
      Morphological features were similar in the 2 groups of patients. ASA involved the
      entire septum in 52% of patients of group AY, and in 47.2% of group BY. The
      prevalence of PFO was 58.8% (95% confidence interval 43-62) in group AY and 28.8%
      in group BY (95% confidence interval 17-35) (chi(2) = 5.811; p = 0.01). A strong
      association was found between ASA and PFO. Of the 90 younger patients with
      stroke, 39 of 44 (88.6%) with ASA also had PFO, compared with 14 of 46 (30.4%)
      without ASA (chi(2) = 7.370; p = 0.007). CONCLUSION: We found that ASA and PFO
      were independent predictive factors for stroke in younger patients with stroke
      and normal carotid arteries and that the association between ASA and PFO bore an
      increased odds risk.

PMID- 12499705
TI  - Chlamydia pneumoniae in elderly patients with stroke (C-PEPS): a case-control
      study on the seroprevalence of Chlamydia pneumoniae in elderly patients with
      acute cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Multiple studies have suggested an association between
      Chlamydia pneumoniae infection and atherosclerotic vascular disease. We
      investigated whether serological markers of C. pneumoniae infection were
      associated with acute stroke or transient ischaemic attack (TIA), exclusively in
      elderly patients. METHODS: One-hundred white patients aged over 65 years admitted
      with acute stroke or TIA, and 87 control patients admitted with acute non
      cardiopulmonary, non-infective disorders were recruited prospectively. Using an
      enzyme-linked immunosorbent assay kit, the presence of C. pneumoniae
      immunoglobulins IgA, IgG, IgM in patients' sera was determined. RESULTS: The
      seroprevalence of C. pneumoniae-specific IgA, IgG, IgM were 63, 71, and 14% in
      the stroke/TIA group (median age = 80), and 62, 65, and 17% in the control group
      (median age = 80), respectively. Using a logistic regression statistical model,
      adjusting for age and sex, history of hypertension, smoking, diabetes, ischaemic
      heart disease (IHD), ischaemic electrocardiogram (ECG), the odds ratios (ORs) of
      having a stroke/TIA in relation to C. pneumoniae-specific IgA, IgG, IgM were
      1.04, 1.24, 0.79 (p = NS). Further analysis identified 43 acute stroke/TIA cases
      and 44 controls without history of IHD or ischaemic ECG or both. After adjusting
      for history of hypertension, smoking, diabetes, age and sex, the ORs in this
      subgroup were 1.40 for IgA [95% confidence interval (CI) 0.53-3.65; p = 0.49],
      2.41 for IgG (95% CI 0.90-6.46; p = 0.08) and 1.55 for IgM (95% CI 0.45-5.40; p =
      0.49). CONCLUSIONS: Although a high seroprevalence of C. pneumoniae in elderly
      patients was confirmed, no significant association between serological markers of
      C. pneumoniae infection and acute cerebrovascular events was found. There was,
      however, a weak trend towards increased ORs for acute cerebrovascular disease in
      a subgroup of C. pneumoniae seropositive elderly patients without any history of
      IHD or ischaemic ECG.

PMID- 12499706
TI  - Heparin treatment in cerebral sinus and venous thrombosis: patients at risk of
      fatal outcome.
AB  - We performed a retrospective analysis of 79 patients with cerebral sinus venous
      thrombosis, who were treated with a fixed regimen of dose-adjusted intravenous
      heparin, to determine predictors of a fatal course. The parameters investigated
      were the state of consciousness and the presence of intracranial haemorrhage
      (ICH) at the start of heparin treatment, involvement of the internal venous
      system, mean delay from initial symptom to stupor or coma and from initial
      symptom to hospital admission, focal neurological deficits, mean intracranial
      circulation time (ICT) on conventional angiography, and age and sex distribution.
      Mortality rate was 10% in this series (8/79). There was a strong link between the
      outcome and the level of vigilance: 53% of the patients with stupor or coma at
      the start of the heparin therapy died (8/15), whereas all of the 64 patients with
      no more than mildly impaired vigilance survived (p < 0.00001). Furthermore, mean
      age and mean ICT were significantly higher in the group of patients who died.
      There was a statistical trend (p = 0.056) for ICH to be more frequent in cases
      with fatal outcome, but there was reason to assume that ICH represented an
      epiphenomenon of a severe course rather than an independent predictor. Other
      investigated parameters were not linked with a fatal outcome.

PMID- 12499707
TI  - The role of chronic alcohol intake in patients with spontaneous intracranial
      hemorrhage: a carbohydrate-deficient transferrin study.
AB  - BACKGROUND AND PURPOSE: Chronic alcohol intake is considered to be a risk factor
      for spontaneous intracranial hemorrhage (SICH). However, there is a lack of
      objective data in this field. The aim was to assess its role in hemorrhagic
      stroke objectively and to evaluate its correlation with the elevation of gamma
      glutamyltransferase (GGT) plasma levels. The reliability of patients' anamnestic
      data concerning alcohol intake was also assessed. METHODS: Laboratory assessment
      of the plasma carbohydrate-deficient transferrin (CDT) level was performed in 105
      SICH patients and in a control group of 105 patients with dorsalgia. All patients
      were treated at the Clinic of Neurology, Faculty Hospital, Olomouc, Czech
      Republic. GGT plasma level values and anamnestic data concerning alcohol
      consumption were also analyzed. chi(2) tests were applied when assessing
      statistical significance. RESULTS: The CDT test was positive in 25.7% of SICH
      patients versus 7.6% of control group subjects (p = 0.0008). GGT plasma levels
      were elevated in 44.4% of SICH patients with a positive CDT test versus 25.6% of
      patients with a negative one. The GGT test is not reliable in the detection of
      alcohol intake when compared with the CDT test (p = 0.71). Only 13.0% of SICH
      patients with a positive CDT test (subgroup 1) stated regular and high
      consumption of all types of alcoholic beverages. Another 26.1% of these patients
      stated regular daily consumption of more than 1 liter, and 47.8% of them stated
      less than 1 liter of beer, with uncertain data concerning wine and spirits
      intake. Thirteen percent of subgroup 1 patients denied alcohol consumption
      altogether. CONCLUSIONS: Chronic alcohol consumption is at least one of several
      risk factors in one fourth of SICH patients in the Olomouc region of the Czech
      Republic. The CDT test is the most sensitive method to diagnose chronic alcohol
      consumption, and it is superior to the examination of GGT and the evaluation of
      patients' anamnestic data.

PMID- 12499708
TI  - Management patterns and health care use after intracerebral hemorrhage. a cost-of
      illness study from a societal perspective in Germany.
AB  - BACKGROUND: The German cost-of-illness study of stroke is a multicenter study in
      6 departments of internal medicine, 9 departments of general neurology and 15
      departments of neurology with an acute stroke unit. The aims of this study are to
      describe the management patterns, cost of treatment and overall resource
      utilization after intracerebral hemorrhage (ICH) as well as the major differences
      to ischemic stroke (IS). METHODS: During a 12-month period, 30 participating
      centers with a special interest in stroke prospectively included 586 patients
      with ICH which were collected in a joint data bank. About 75% of all patients
      could be centrally followed up via structured telephone interviews after 3 and 12
      months to assess further acute hospital and rehabilitation stays, outpatient
      resource utilization, functional outcome and quality of life. RESULTS: Mortality
      after 3 months (33.5%) was markedly higher than in patients with IS from the same
      hospitals. Accordingly, only 30.9% of patients had regained independent
      functional status after 3 months. Cumulative cost of treatment amounted to 5301
      EUR for inpatient stay in the documenting hospital and 8920 EUR for the overall
      hospital stay including rehabilitation. Mean direct cost after discharge during
      the first year amounted to 4598 EUR and the loss of work force was equivalent to
      5537 EUR in all surviving patients. CONCLUSION: This study provides a
      comprehensive overview of patient characteristics, treatment strategies and
      health care cost of ICH from a societal perspective in Germany.

PMID- 12499709
TI  - Stroke in HIV-infected patients: a clinical perspective.
AB  - The occurrence of stroke in patients with human immunodeficiency virus (HIV)
      infection has been traditionally associated with opportunistic infections and
      tumors, and advanced stages of immunosuppression. However, this reality is
      undergoing major changes. Effective antiretroviral regimens are now able to
      forestall the progression of HIV infection and avoid early mortality. As HIV
      infected patients are growing older, clinicians are facing new challenges,
      including an increasing incidence of vascular complications. The use of protease
      inhibitors is associated with a variety of metabolic derangements that could
      produce accelerated atherosclerosis. Cerebrovascular hemodynamic function is
      impaired in HIV-infected patients with evidence of abnormal vasoreactivity even
      in otherwise healthy individuals. The potential contribution from these novel
      mechanisms should be added to the high incidence of classic vascular risk factors
      in the HIV-infected population and the cardiac abnormalities frequently observed
      in these patients. Large-scale epidemiological studies should be carried out to
      define the true incidence of stroke in HIV-infected patients and the factors
      associated with its occurrence.

PMID- 12499710
TI  - Administration of nonionic iodinated contrast medium does not influence the
      outcome of patients with ischemic brain infarction.
AB  - Some reports indicate that exposure to iodinated contrast medium (CM) could
      worsen the outcome of patients with brain infarction. In this prospective study,
      we compared the outcome of 77 patients receiving and 128 not receiving nonionic
      iodinated CM. Stroke severity was assessed by the Scandinavian Prognostic Stroke
      Score, and outcome by the Rankin Scale. All radiological studies using
      intravenous or intra-arterial CM were registered. Two nonionic iodinated CM
      (iopamidol and iohexol) were used. Exposure to CM did not influence case
      fatality, ability to live at home, ability to walk, disability and stroke
      severity. Initial stroke severity and arterial hypertension were independent
      determinants of poor neurological recovery or death. Large infarct, age, male
      gender, and baseline stroke severity were independent determinants of major
      disability or death. CM enhancement on CT did not show any harmful effect on
      stroke severity or outcome. As a conclusion, intravascular administration of
      nonionic iodinated CM did not influence stroke severity or outcome of our
      patients.

PMID- 12499711
TI  - Polymorphisms of platelet adhesive receptors: do they play a role in primary
      intracerebral hemorrhage?
AB  - BACKGROUND: Several reports suggested that polymorphisms affecting the structure
      or level of the main adhesive platelet glycoproteins (GPs) could behave as
      genetic risk factors for arterial thrombotic disorders. However, very few reports
      analyzed the significance of these polymorphisms in bleeding disorders.
      Interestingly, one study suggested a role of the 807 C/T polymorphism of the
      collagen receptor GP Ia in the severity of the bleeding manifestations in von
      Willebrand disease. The aim of this study was to evaluate the role of frequent
      polymorphisms affecting platelet GPs in primary intracerebral hemorrhage (PIH),
      the third most frequent cause of cerebrovascular disorder. METHODS: We evaluated
      the role of four putative prothrombotic polymorphisms: GP Ia [807 C/T, and human
      platelet alloantigen system 5 (HPA-5)], GP Ibalpha (variable number of tandem
      repeats), and GP IIIa (HPA-1) in 141 Caucasian patients diagnosed of PIH, 141
      race-, age-, sex- and risk factor-matched controls, and 446 subjects from the
      general population. RESULTS: The frequency of genotypes and alleles were similar
      between patients and controls. CONCLUSIONS: Our results suggest that these
      polymorphisms play a minor role in PIH.

PMID- 12499712
TI  - Complaints of poststroke insomnia and its treatment with mianserin.
AB  - We assessed the prevalence and associations of symptoms of insomnia in patients
      with acute ischemic stroke, and evaluated whether mianserin as a sedative
      antidepressant is beneficial in the treatment of poststroke insomnia. One hundred
      consecutively hospitalized patients were randomized to receive 60 mg/day of
      mianserin (n = 51) or placebo for 1 year in a double-blind trial with a 6-month
      follow-up after the therapy. Symptoms of insomnia were assessed with the three
      insomnia-related items of the Hamilton Depression Scale; patients were defined as
      insomniacs if any of these items was positive. Complaints of insomnia occurred in
      68% of patients on admission, and in 49% at 18 months, and they were as frequent
      in all subgroups of patients. From 2 months, symptoms of insomnia were associated
      independently with depression. Living alone before stroke (at 0 and 2 months) and
      age (at 12 months) were other independent predictors of insomnia. The rate of
      recovery as evaluated by the insomnia score was more rapid in patients on
      mianserin than in those on placebo. At 2 months, the scores were significantly
      different favoring mianserin treatment (1.3 vs. 0.8, p = 0.02). We conclude that
      insomnia is a common complaint after ischemic stroke. Mianserin had a beneficial
      influence on the recovery from symptoms of insomnia, even though the intensity of
      poststroke depression was low.

PMID- 12499713
TI  - High leptin levels are associated with stroke.
AB  - BACKGROUND AND PURPOSE: Leptin, an important hormone for body weight regulation,
      may be involved in the pathogenesis of cardiovascular manifestations of obesity.
      We tested whether leptin may be an independent risk marker for stroke in a case
      referent study. METHODS: Definitive acute stroke events, defined by MONICA
      criteria, were identified from October 1, 1995 to April 30, 1999. Referents
      without known cardiovascular disease were randomly selected from a population
      census. Patient characteristics were taken from hospital files and leptin was
      analyzed in stored samples. Logistic regression analysis was used to determine
      possible differences in leptin levels between groups. RESULTS: One hundred and
      thirty-seven cases with ischemic stroke and 69 cases with hemorrhagic stroke were
      identified. In comparison with referents, male patients with stroke had
      significantly higher leptin levels. Both male and female stroke patients had
      increased blood pressure compared with the referents. In multivariate analyses,
      high leptin levels were associated with both ischemic (OR = 4.89; 95% CI: 1.89
      12.62) and hemorrhagic (OR = 3.86; 95% CI: 1.13-13.16) stroke in men, and with
      ischemic stroke in women (OR = 4.10; 95% CI: 1.45-11.62). The combination of high
      leptin levels and increased blood pressure (systolic or diastolic) was associated
      with a strong positive interaction in males with hemorrhagic stroke. CONCLUSION:
      Leptin may be an important link for the development of cerebrovascular disease in
      the insulin resistance syndrome in men.

PMID- 12499714
TI  - Two-peak temporal distribution of stroke onset in Greek patients. a hospital
      based study.
AB  - A circadian distribution with a single peak of stroke onset in the morning hours
      has been described in various countries. Analysis of the temporal pattern of
      symptom onset in a series of 1253 Greek first-ever stroke patients revealed a
      circadian distribution with two incidence peaks between 08.00 and 10.00 h, and
      between 16.00 and 18.00 h. Considering the different etiopathogenic types of
      stroke, the same two-peak time pattern was evaluated in all stroke subgroups with
      the only exception of lacunar stroke, which seems to predominantly occur during
      night and sleep. A secondary stroke onset peak in the late afternoon has not been
      previously described in such detail. A relation between the second, however
      lower, frequency peak and the traditional Greek habit of afternoon sleep (siesta)
      could be assumed and deserves further investigation.

PMID- 12499715
TI  - Seizures in cerebral vein and dural sinus thrombosis.
AB  - To describe early symptomatic and late seizures in a cohort of patients with
      acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their
      determinants, we performed a prospective registry and follow-up study of CVDST
      patients admitted to 20 Portuguese hospitals, from June 1995 to June 1998. Of 91
      registered patients, 31 (34%) had early symptomatic seizures; 29 (31.9%) as a
      presenting feature and 2 (2.1%) after admission. Early symptomatic seizures were
      more frequent in patients with motor and sensory deficits and in those with focal
      oedema/ischaemic infarcts or haemorrhages on admission CT/MR. On multivariate
      logistic regression analysis, sensory defects (OR = 7.8; 95% CI = 0.8-74.8) and a
      parenchymal lesion on admission CT/MR (OR = 3.7, 95% CI = 1.4-9.4) were found to
      be significant predictors of early symptomatic seizures. Seizures were directly
      related to acute death in 2 patients. Eight (9.5%) patients had late seizures,
      which were multiple in 4 (4.8%). Late seizures were more frequent in patients
      with early symptomatic seizures and with haemorrhage on admission CT/MR. Neither
      early symptomatic seizures nor late seizures were related to functional prognosis
      at the last follow-up (median = 1 year). There is a moderate risk of seizure
      recurrence early in the course and during the first year after CVDST. Seizures
      can be a cause of acute death, but might not have an independent influence on
      functional outcome. Pharmacological prevention of seizures after CVDST should
      probably be limited to patients with early symptomatic seizures and cerebral
      lesions on admission CT/MR.

PMID- 12499716
TI  - Early outcome of carotid angioplasty and stenting versus carotid endarterectomy
      in a single academic center.
AB  - BACKGROUND: Evidence is accumulating that carotid angioplasty and stenting (CAS)
      might become an alternative to carotid endarterectomy (CEA) for the treatment of
      high-grade carotid artery disease (CAD). Evaluating the efficacy of this novel
      technique in single institutions in addition to performing further large trials
      can help to guide optimal patient management in everyday practice. METHODS: In
      this study we compared the early outcome of 100 prospectively followed patients
      who underwent CAS with a retrospectively reviewed group of 142 patients that
      underwent CEA over the same time period. Only patients who had received pre- and
      postsurgical evaluations by a neurologist were included. According to the
      criteria set forth by the large trials the occurrence of minor or major strokes,
      myocardial infarction and death within 30 days was analysed. RESULTS: Both groups
      had similar age and sex distributions, as well as cerebrovascular risk factors.
      In the group of CAS patients 63 (63%) and in the group of CEA patients 92 (65%)
      had a symptomatic carotid stenosis, respectively. For symptomatic patients the
      overall complication rate (any stroke or death) was 6.5% (3 minor and 3 major
      strokes) in the surgical and 8% (2 minor strokes, 2 major strokes, and 1 death)
      in the non-surgical group (n.s.). For asymptomatic patients there was one minor
      stroke (2%) in the surgical and no stroke or death in the non-surgical group. As
      a frequent non-neurological complication the post-procedural course was
      complicated by groin hematoma requiring surgery in 3 CAS patients, and neck
      hematoma requiring additional surgery in 3 CEA patients. CONCLUSIONS: Within our
      academic institution we found comparable complication rates for CAS and CEA in
      patients with symptomatic or asymptomatic high-grade CAD. Although these early
      results are promising and support the notion that CAS may become an alternative
      treatment option for CAD in everyday practice, the long-term efficacy of CAS has
      to be evaluated critically by means of further prospective studies.

PMID- 12499717
TI  - Percutaneous transluminal angioplasty for symptomatic middle cerebral artery
      stenosis: long-term follow-up.
AB  - BACKGROUND AND OBJECTIVE: Although percutaneous transluminal angioplasty (PTA) is
      an effective treatment modality in the coronary and peripheral arterial diseases,
      its efficacy for intracranial atherosclerotic stenosis has not been verified. We
      assessed the long-term outcome of PTA for symptomatic middle cerebral artery
      (MCA) stenosis. METHODS: We performed PTA in 10 patients with symptomatic high
      grade stenosis (>70%) on M1 segment of MCA, who had either recurrent transient
      ischemic attacks (TIAs) resistant to medical therapy or perfusion problems. PTA
      was performed with a microballoon (2-2.5 mm diameter and 10-13 mm length) without
      insertion of a stent. After PTA, we evaluated the possible occurrence of
      restenosis, which was defined as >50% stenosis on follow-up conventional
      angiogram or increased M1 flow velocity on follow-up transcranial doppler up to
      the baseline value. RESULTS: PTA was successfully performed in 9 patients without
      any serious complications. One patient had asymptomatic dissection. Residual
      stenosis was less than 50% in diameter in all the patients. During follow-up
      period (mean 34.5 months), TIAs did not recur in 6 of 7 patients who had had
      intractable TIAs. Two patients developed strokes, which were not referable to the
      index MCA lesions. Among the 6 patients who underwent follow-up conventional
      angiography or serial TCD, restenosis was noticed in 3 patients (50%).
      CONCLUSION: Although restenosis is not uncommon, PTA for symptomatic MCA stenosis
      is a relatively safe procedure, and can be used to prevent recurrent TIAs or
      strokes in selected patients.

PMID- 12499718
TI  - Aging and stroke rehabilitation. a case-comparison study.
AB  - The aim of this study was to assess the specific influence of age on basal
      functional status and rehabilitation results. We conducted a case-comparison
      study on 150 stroke inpatients. They were enrolled in homogeneous subgroups,
      matched for severity of stroke (measured by Canadian Neurological Scale - CNS)
      and onset admission interval (within 3 days) and divided into five subgroups
      according to age: <or=50; 51-64; 65-74; 75-84; and >or=85 years. Even when
      severity of stroke was the same, increasing age was associated with greater
      disability in activities of daily living (ADL) and mobility, minor results of
      rehabilitation treatment and shorter length of stay. Patients >or=85 years were
      nearly ten times as likely to show a low response in ADL (OR = 9.28, 95% CI =
      2.89-29.76) and nearly six times in mobility (OR = 6.13, 95% CI = 2.18-17.25)
      than younger patients. However, rehabilitation treatment was efficacious also in
      patients >or=85 years, with effectiveness of treatment 27.96% on ADL and 18.64%
      on mobility. On one hand our results confirm the unfavorable influence of age on
      functional outcome and on the other that inpatient rehabilitation is
      substantially effective also for very old patients, although less than for
      younger ones.

PMID- 12499719
TI  - Functional outcome, rehabilitation use and length of hospital stay for stroke
      patients in south Madrid.
AB  - BACKGROUND: Health status and use of resources by stroke patients in Spain are
      unknown. METHODS: A total of 103 acute stroke patients resident in south Madrid,
      population 665,168, were seen in 1996 at a general hospital and three primary
      care centres and evaluated at 5-10 days, 3 and 6 months after stroke. Health
      outcomes and patterns of rehabilitation and hospital use by patient groups were
      studied using multivariate logistic regression. RESULTS: The group receiving
      rehabilitation exhibited higher levels of impairment, disability and handicap at
      each time point, these differences decreasing with time, except in the
      distribution of walking ability which was unimodal in that group. Younger age,
      poor walking ability and motor capacity, pain on the paretic side and living with
      a spouse predicted use of rehabilitation; low level of education predicted a long
      hospital stay. CONCLUSION: Rehabilitation for stroke in south Madrid was sparse
      and used mainly by young, severely affected patients.

PMID- 12499720
TI  - Sensitivity of the dementia rating scale in vascular dementia: comparison between
      two sets of criteria to define cognitive impairment.
AB  - BACKGROUND: The Dementia Rating Scale (DRS) is a common measure of cognitive
      function, but its sensitivity to identify deficits across cognitive domains in
      vascular dementia (VaD) remains unclear. METHODS: We compared the sensitivity and
      specificity of two recommended cutoff scores of the DRS. Thirty-eight patients
      diagnosed with VaD participated in the current study. RESULTS: The original
      recommendations resulted in poor sensitivity for the DRS total score and
      attention, construction, and memory subscales. The more recent recommendations
      greatly improved the sensitivity of the subscales and the total DRS score, but
      resulted in decreased specificity. Correlations between the specific DRS
      subscales and criterion measures of cognitive function revealed good convergent
      and divergent validity for most subscales. CONCLUSIONS: The DRS is a valid
      measure of cognitive dysfunction in VaD, but clinicians should consider using the
      more recent recommendations developed for AD to determine impaired performances
      in VaD.

PMID- 12499722
TI  - Measurement of global cerebral circulation time using power duplex echo-contrast
      bolus tracking.
AB  - Ultrasound assessment of global cerebral circulation time (CCT) using echo
      contrast bolus tracking is a new approach to characterise the perfusion status of
      the human brain. We present the analysis of global CCT in 36 healthy volunteers
      and one patient with a cerebral arteriovenous malformation (AVM), measured by
      extracranial power duplex. CCT was defined as the time interval between bolus
      arrival in the internal carotid artery and internal jugular vein. CCT in the
      volunteer group was 7.5 +/- 1.1 s (mean +/- SD). Values did not correlate with
      age, gender, blood pressure or blood flow velocity. Measurement in the AVM
      patient revealed a CCT of 1.5 s. Ultrasonographic CCT analysis is a promising new
      tool for the evaluation of cerebral hemodynamics.

PMID- 12499721
TI  - Ischaemic stroke in young people: a prospective and long-term follow-up study.
AB  - BACKGROUND: A few studies have comprehensively assessed the epidemiology,
      aetiology, prognosis, and secondary prevention of ischaemic stroke in young
      adults. To gain further information on this field, we have prospectively studied
      a hospital-based series of young adults with a first-ever episode of cerebral
      ischaemia (CI). METHODS: Sixty consecutive patients aged 17-45 with ischaemic
      stroke (55 patients) or transient ischaemic attack within 24 h before hospital
      admission were recruited and investigated by a standardized rigorous protocol.
      The patients were followed up for >or=1 year after hospital discharge. Arbitrary
      doses of aspirin 100 mg/d or ticlopidine 250 mg b.i.d. in case of intolerance to
      aspirin were given for the secondary prevention. Adjusted-dose oral
      anticoagulation (INR target 2.5) was used in the presence of cardioembolism or
      hypercoagulable states. Endpoints included the residual disability, rated by
      modified Rankin Scale (RS) and Barthel Index (BI), and poststroke recurrence.
      RESULTS: CI was associated with two or more risk factors in 61.6% of patients.
      Cigarette smoking was more frequently associated with male gender (p < 0.05) and
      migraine history with female sex (p < 0.05). The atherothrombotic diagnostic
      subtype and the subtype from 'other cause' predominated significantly among
      patients >or=35 years old (p < 0.05) and <35 years (p < 0.025), respectively. The
      'other cause' subset was more frequent in female gender (p < 0.05).
      Transoesophageal echocardiography (TEE) detected potential cardiac sources of
      emboli (PCSE) at an extent 3 times higher (p < 0.0001) than transthoracic
      echocardiography. Congenital heart defects were nearly threefold more frequent
      than acquired ones, with a prevalence of patent foramen ovale. At a mean of 6.1
      +/- 2.6 years (confidence interval 5.4 to 6.8), follow-up data were available for
      only 54 patients, since five patients were lost and one died in the acute phase.
      Poststroke recurrence rate was low (7.4%) and no event was fatal. General
      handicap was severe to moderately severe (RS>3) in 11% of the patients, slight to
      moderate (1>or=RS<or=3) in 59% and absent in 30% (RS = 0). Functional disability
      was relatively low with 50% of the patients independent (BI >or=95), 38.9%
      partially dependent (BI 60 to 86), and 11.1% fully dependent (BI <60). Thirty
      seven (68.5%) patients returned to work, although adjustments (other job or part
      time employment) were necessary for 10 out of them (27%). CONCLUSIONS: The
      present study, though limited by the relatively small number of subjects,
      suggests that the overall prognosis of ischaemic stroke in young adults is good.
      We strongly recommend TEE in all patients with ischaemic stroke as an essential
      tool to increase the detection of PCSE and make the therapeutic approach more
      efficient.

PMID- 12499723
TI  - Incidence and outcome of subtypes of ischaemic stroke: initial results from the
      north East melbourne stroke incidence study (NEMESIS).
AB  - Information about the incidence and outcome of stroke subtypes is necessary to
      understand the likely impact of stroke prevention and treatment strategies. The
      purpose of this study was to determine the incidence and outcome of subtypes of
      cerebral infarction (CI). All strokes occurring in a population of 133816 in
      Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified
      and cases of CI subtyped according to the Oxfordshire Community Stroke Project
      classification. 276 'first-ever-in-a-lifetime' stroke cases were registered. CI
      accounted for 72% of cases. Annual incidence rates per 100000 persons adjusted to
      the 'world' population were 11 (95% CI, 4-18) for TACI, 25 (95% CI, 15-35) for
      PACI, 17 (95% CI, 9-25) for POCI and 18 (95% CI, 10-26) for LACI. 28-day case
      fatality was highest for TACI (35%; 95% CI, 19-51%) and first year recurrence
      rate highest for PACI (17%; 95% CI, 8-26%). TACI had the poorest functional
      outcome at 3 and 12 months. These findings are similar to those of two previous
      studies conducted in the northern hemisphere.

PMID- 12499724
TI  - Diffuse capillary telangiectasia of the brain manifested as a slowly progressive
      course.
AB  - Brain capillary telangiectasia (BCT) are usually small, solitary, benign in
      clinical manifestation, or found incidentally at autopsy. However, diffuse BCT
      are rarely reported. A 39-year-old woman had the first generalized seizure 10
      years previously. Thereafter, she had sustained progressive spastic paraparesis
      and blurred vision. Computed tomography (CT) showed diffuse brain atrophy with
      numerous calcified spots. Contrast T1-weighted magnetic resonance images showed
      diffuse faintly enhancing lesions with stippled appearance in the whole brain.
      Cerebral angiography revealed multiple small nets of dilated capillaries and
      Xenon CT showed diffuse low cerebral blood flow in the resting and good cerebral
      reserve capacity in the acetazolamide challenge test. Therefore, diffuse BCT was
      diagnosed clinically. Although BCT are not rare, diffuse BCT with slowly
      progressive neurological symptoms had never been reported before. It causes
      global cerebral ischemia that lead to brain atrophy and a degenerative course.

PMID- 12499725
TI  - Combined cerebellar and bilateral cervical posterior spinal artery stroke
      demonstrated on MRI.
AB  - Combined cerebellar and spinal ischemic stroke is a rare, critical condition. We
      report a patient with combined cerebellar and bilateral posterolateral cervical
      spinal cord infarction due to bilateral stenosis of the vertebral arteries. MRI
      is the method of choice for imaging this condition; diffusion-weighted imaging of
      the spinal cord gives reliable results.

PMID- 12499726
TI  - Medial medullary infarction after coronary stent angioplasty.

PMID- 12499727
TI  - 'Fou rire prodromique' and choroidal anterior artery stroke.

PMID- 12499728
TI  - Pure alexia and hemianopia related to dissection of the internal carotid artery.

PMID- 12499729
TI  - It is necessary to prevent a cerebrovascular 'pandemia'.

PMID- 12499730
TI  - Hyperglycaemia in patients after intravenous thrombolysis.

PMID- 12499732
TI  - Stroke in a chiropractic patient population.

PMID- 12499734
TI  - Common carotid artery occlusion.

PMID- 12499735
TI  - Evidence-Based Minimally Invasive Surgery in Oncology. Proceedings of the Joint
      Meeting of German Speaking Societies for Minimally Invasive Surgery. March 21-23,
      2002, Heidelberg, Germany.

PMID- 12499736
TI  - Are "micrometastases" of the peritoneum equivalent to distant metastases?
AB  - Tumor progression after curative resection of gastrointestinal cancer is probably
      caused by disseminated tumor cells that can be detected in different body
      compartments, e.g. the peritoneum. The clinical importance and prognostic
      significance of gross peritoneal metastasis is well known whereas the prognostic
      relevance of disseminated tumor cells in the peritoneum of patients with
      gastrointestinal cancer is still unclear. Disseminated tumor cells in the
      peritoneal cavity are generally detected by cytology, immunohistochemistry or
      polymerase chain reaction-based molecular methods. A consensus on the most
      adequate detection method has not yet been found making the comparison of
      different data difficult. The prognostic relevance of tumor cell dissemination
      has, at least in part, been shown for gastric, pancreatic and colon cancer, and
      the prognostic data regarding gastric cancer are most convincing. Peritoneal
      "micrometastases" are obviously not equivalent to distant metastases as the
      evidence for their prognostic significance is clearly less than that for gross
      peritoneal metastases. This article gives a critical review of the detection and
      prognostic significance of disseminated tumor cells in the peritoneum of patients
      with gastrointestinal cancer.

PMID- 12499737
TI  - Immunologic changes during minimally invasive surgery.
AB  - Although recent experimental and clinical trials have documented that
      postoperative inflammation and changes in different immunologic parameters are
      less pronounced after laparoscopic approaches in comparison to open surgery, it
      still remains unclear what influence the pneumoperitoneum itself has on
      immunologic defense and function. This is mainly due to the endpoints of the
      different studies which investigate changes in the so-called immunologic
      parameters (cell subunits, C-reactive protein, cytokines, catecholamines or other
      stress hormones in plasma samples) rather than analyzing immunologic functions,
      such as cell activation, production of proteins, cell proliferation or in vivo
      immune defenses. So far, especially in clinical trials, no correlation has been
      demonstrated between the changes in immunologic parameters and relevant
      postoperative clinical endpoints, such as postoperative complications. Thus
      further clinical prospective randomized studies with relevant clinical endpoints
      and additional investigations of immunologic parameters are needed to prove the
      consequences of either minimally invasive surgery or open procedures on
      postoperative immune functions.

PMID- 12499738
TI  - Tumor cell dissemination during laparoscopy: prevention and therapeutic
      opportunities.
AB  - Port-site recurrences (PSRs) are abdominal wall recurrences that occur in the
      subcutaneous tissue within a trocar site after cancer laparoscopy and are not
      associated with peritoneal carcinomatosis. In order to develop PSRs, viable tumor
      cells must be liberated from the primary tumor, be transported to a wound, and
      find there a favorable environment for growth. The short clinical delay in the
      occurrence of PSRs and their size suggest massive cell seeding into the abdominal
      wall. Traumatic handling of the tumor, slipping of trocars, liquid projection, as
      well as poor extraction techniques can all cause implantation of malignant cells
      into the subcutaneous tissue. Such contact can also occur postoperatively if the
      trocar channels remain open. Some histologies (e.g. gallbladder adenocarcinoma),
      the presence of ascites and advanced tumor stage are risk factors for PSRs.
      Further conditions--including the use of gas--might also play a limited role. The
      first preventive measure is the correct indication for a laparoscopic approach.
      Several techniques have been demonstrated to prevent PSRs in the animal model:
      (a) fixation of trocars to the abdominal wall; (b) prevention of leakage; (c)
      careful specimen handling; (d) reducing trauma to the abdominal wall; (e)
      specimen isolation before extraction from the abdominal cavity; (f) trocar-site
      irrigation with a cytotoxic solution, and (g) closure of peritoneum. Further
      innovative therapies are currently under investigation. In the clinical setting,
      correct indication, surgical expertise and application of prophylactic measures
      seem to be the best way to prevent the occurrence of PSRs.

PMID- 12499739
TI  - Technique and value of staging laparoscopy.
AB  - Despite significant improvements in preoperative tumor staging due to
      sophisticated new imaging and interventional techniques, peritoneal tumor spread
      and occult liver and lymph node metastases are only detected during surgery in
      some patients. Newer treatment modalities using neoadjuvant regimens are only
      given if occult tumor spread is excluded. Diagnostic laparoscopy has therefore
      been introduced to prevent patients with advanced tumor disease from unnecessary
      laparotomy and as a diagnostic tool in neoadjuvant treatment protocols.
      Laparoscopic ultrasound represents an important technical improvement in
      diagnostic laparoscopy. The main indication for diagnostic laparoscopy is
      therefore exact tumor staging, especially in terms of peritoneal, liver, and
      lymphatic tumor spread, whereas determination of local tumor resectability is not
      the main issue. The aim of the current review is to summarize the technique of
      staging laparoscopy and to discuss its clinical value for a variety of
      gastrointestinal malignancies.

PMID- 12499740
TI  - Is there additional information from laparoscopic ultrasound in tumor staging?
AB  - Accurate preoperative staging of gastrointestinal malignancies is of major
      importance in the decision for adequate stage-related therapy. There is evidence
      that laparoscopy in combination with laparoscopic ultrasound is more accurate in
      the detection of intra-abdominal metastases than conventional preoperative
      imaging. Staging laparoscopy in combination with laparoscopic ultrasound is a
      minimally invasive technique that reveals intra-abdominal disseminated tumor
      spread and local tumor extent. Therefore laparoscopic ultrasound is an ideal
      adjunct to laparoscopy because this technique may compensate for the lack of
      tactile feedback with laparoscopic instruments. Color-coded Doppler imaging can
      be very valuable for the assessment of resectability in patients with pancreatic
      cancer. Current data confirm that laparoscopic ultrasound is capable of enhancing
      the accuracy of staging laparoscopy. Compared to standard laparoscopy, a
      combination of both techniques markedly increases the sensitivity of staging
      laparoscopy in the determination of unresectable disease. This is of major
      importance in the assessment of occult liver metastases and lymph node
      involvement. Laparoscopic ultrasonography improves the diagnostic accuracy
      compared to conventional imaging techniques and should be considered as integral
      part of staging laparoscopy.

PMID- 12499741
TI  - Staging laparoscopy and its indications in pancreatic cancer patients.
AB  - BACKGROUND: Laparoscopy has become a popular and widespread surgical technique.
      An important goal in the treatment of patients with pancreatic cancer is to avoid
      any unnecessary procedure. Laparoscopy has been suggested as a routine tool for
      staging in order to prevent unnecessary laparotomies in these patients. METHODS:
      In this article we present our experience regarding the value of laparoscopic
      staging and review the literature on this topic. RESULTS AND CONCLUSION: A direct
      and conclusive comparison of the controversial literature is difficult because of
      different study designs. Inconsistent use of high-quality CT scans significantly
      affects the results. However, recent studies reveal that not more than 14% of the
      patients benefit from diagnostic laparoscopy when a state-of-the-art CT scan has
      been performed previously. Therefore, we conclude that routine diagnostic
      laparoscopy is not justified in all patients with pancreatic cancer. Rather,
      selective use is appropriate, especially in patients in whom ascites is an
      indirect sign of peritoneal metastases, or if liver metastases cannot be surely
      excluded preoperatively. This approach is cost-effective and limits diagnostic
      laparoscopy to a subgroup of patients in whom a laparotomy can be avoided.

PMID- 12499742
TI  - Intraoperative suspicion of gallbladder carcinoma in laparoscopic surgery: what
      to do?
AB  - The frequency of gallbladder cancer in Europe is less than 1% of all gallstone
      operations. With the introduction of laparoscopic surgery and the higher
      acceptance of this technique, patients with gallstones have gallbladder removal
      much earlier in their gallstone history. So the percentage of gallbladder
      carcinomas will decrease in the future. We report on our surgical procedures in
      patients with suspicious gallbladders having laparoscopic gallbladder removal,
      and how to proceed after the diagnosis of gallbladder carcinoma. From June 1990
      to December 2001, we have performed 7,130 cholecystectomies in a single
      department. 47 of these patients (0.66%) were identified as having carcinoma.
      There were 40 females and 7 males, with a mean age of 70.6 years. In 17 cases
      (36%) there was a preoperative suspicion of malignancy. Most commonly, in 30
      cases (64%), malignancy was suspected intraoperatively or diagnosed
      postoperatively after pathological examination of the resected gallbladder. We
      recommend removal with a bag for all gallbladders with a suspected wall or
      scleroatrophic calcified gallbladder area. In stage Tis or T1 laparoscopy +
      cholecystectomy is sufficient. For T2 and T3 we perform reoperation with liver
      bed resection and lymphadenectomy.

PMID- 12499743
TI  - Role of laparoscopy in hepatic cyst surgery.
AB  - BACKGROUND: Hepatic cysts are detected incidentally in 2.5-5% of the population.
      Only about 15% of such cysts are symptomatic. Since laparoscopic deroofing for
      liver cysts was first described in 1991 there have been a number of reports of
      successful laparoscopic management of hepatic cysts, including the laparoscopic
      management of complex and parasitic cysts. METHODS: A systematic review of
      English-language articles on the subject appearing in journals through May 2002
      was conducted using the Medline database. RESULTS: Only a minority of cystic
      liver lesions need treatment, and the therapeutic approach is guided by the type
      of cyst. Laparoscopic deroofing (combined with omentoplasty and/or oversewing) of
      uncomplicated liver cysts is associated with a recurrence rate of 10-25%, with
      less morbidity and mortality as compared to open surgery. On the other hand,
      treatment of complex liver cysts and hydatid cysts by laparoscopy is not
      considered a standard approach. CONCLUSION: The laparoscopic approach in
      uncomplicated but symptomatic liver cysts is effective, with low morbidity and
      mortality. Additional omentoplasty or oversewing appears to reduce the recurrence
      rate.

PMID- 12499744
TI  - Technique of mobilization and mesh fixation in laparoscopic hernia repair by
      transabdominal preperitoneal mesh prosthesis.
AB  - In laparoscopic inguinal hernia repair the preparation technique is very
      important to avoid recurrences. A standardized dissection, mesh placement and
      fixation with staplers provides safe closure of every inguinal and femoral
      hernia.

PMID- 12499745
TI  - Specimen retrieval in laparoscopic colon surgery.
AB  - In the past decade, for benign as well as malignant colon diseases, minimally
      invasive surgery has gained more and more importance in colon surgery. Specimen
      retrieval after colonic resections is difficult due to the large size of the
      specimen usually resected. To date there is no standardized retrieval technique
      for the different procedures. Four incision sites are common for transabdominal
      specimen retrieval: left or right lower quadrant transrectal portside incision;
      periumbilical midline incision, and transverse suprapubic incision. Perineal
      incisions are used for retrieval following low anterior resection or abdomino
      perineal extirpation. Three major complications are described in the literature:
      wound infection (0-9%); hernias (0-2%), and incision site recurrence (0-1.3%).
      There are no significant differences between the different incision sites with
      regard to the occurrence of complications. In laparoscopic surgery for malignant
      diseases retrieval is usually performed using a plastic bag, whereas retrieval
      can be performed hand-assisted without a bag during surgery for benign diseases.
      Wound edge protectors are recommended by several authors, yet there is no
      standard system which is accepted broadly. In conclusion, specimen retrieval in
      laparoscopic colon surgery is not standardized. The morbidity rate for specific
      retrieval complications ranges between 0 and 9%, yet there are no randomized
      controlled studies or evidence-based data regarding different retrieval
      approaches and systems.

PMID- 12499746
TI  - Laparoscopic resection of the left pancreas: technique and indication.
AB  - Laparoscopic pancreatic resections are rare procedures. A particular position is
      held by the left resection. In animal trials and 37 operations performed to date,
      this laparoscopic procedure has been positively assessed. The diseases operated
      upon were nearly exclusively benign. From November 1998 to July 2001, we
      performed 5 laparoscopic distal pancreatic resections at our hospital. The
      indications were: 2 adenocarcinomas; 1 neuroendocrine carcinoma; 1 high malignant
      T-cell lymphoma, and 1 cystadenoma. Additional procedures in 3 patients were:
      gastrectomy and resection of the left liver in the case with T-cell lymphoma;
      resection of a distant metastasis in the liver in the case with advanced
      pancreatic carcinoma, and a partial adrenalectomy in the case with cystadenoma.
      We did not note any intra- or postoperative complications in our patients. First
      of all, benefit is to be found in the early postoperative course. All
      oncosurgical criteria could be fulfilled.

PMID- 12499747
TI  - Endoscopic inguinal hernia repair in comparison with Shouldice and Lichtenstein
      repair. A systematic review of randomized trials.
AB  - AIMS: This article provides an overview of randomized studies which compare
      endoscopic hernia repair techniques (TAPP/TEP) with the Shouldice and
      Lichtenstein repair. METHODS: Systematic analysis of 33 published studies which
      meet the criteria of a randomized controlled trial with a high evidence level.
      RESULTS: The majority of the studies document statistically significant
      advantages of the endoscopic repair techniques in relation to wound pain (15/22),
      need for analgesics (16/21), return-to-work time (16/22) and physical activity
      (18/25), although only one study showed significant advantages of the
      Lichtenstein method. Six of 28 studies showed a lower morbidity in comparison to
      open approaches, although 22 of 28 studies documented no significant difference.
      The first long-term studies with follow-up periods between 5 and 6 years also
      show advantages of the endoscopic techniques. CONCLUSION: Even with cautious
      interpretation of the data, it is clear that endoscopic techniques are more
      comfortable for patients and that morbidity is no higher than for open
      procedures. Due to the short follow-up periods final evaluation regarding long
      term complications and recurrence is not yet possible.

PMID- 12499748
TI  - Laparoscopic versus open appendectomy: between evidence and common sense.
AB  - BACKGROUND: Laparoscopic surgery has been proposed to have diagnostic and
      therapeutic advantages over conventional surgery. The purpose of this article is
      to present a recently completed Cochrane review on laparoscopic surgery for
      suspected appendicitis on the background of daily surgical practice and the
      developments in the last decade. METHODS: Within the Cochrane review, various
      medical databases (Medline, Embase, Cochrane, SciSearch) were searched
      electronically until October 2001. Congress proceedings were searched by hand.
      Randomized controlled trials were included that assessed the therapeutic effects
      of laparoscopic appendectomy (LA) versus open appendectomy (OA) in adults and
      children, the diagnostic effects of laparoscopy followed by LA or OA if necessary
      versus immediate OA, and the therapeutic effects of diagnostic laparoscopy
      followed by OA if necessary versus immediate OA. RESULTS: Based on 45 studies,
      wound infection was half as likely while intra-abdominal abscesses were three
      times more frequent after LA. Return to normal activity showed a uniform tendency
      in favor of LA. Pain was also reduced, but data vary and most primary studies
      were not blinded. Obvious diagnostic advantages concerned the negative
      appendectomy rate and the rate of patients without established diagnosis, both
      being reduced to 0.2-0.3 (RR). CONCLUSION: The review finds that laparoscopic
      surgery for suspected appendicitis has diagnostic and therapeutic advantages as
      compared to conventional surgery--a fact which is in full agreement with the
      daily practice of surgeons interested in endoscopic surgery.

PMID- 12499749
TI  - [Science and law in assisted reproductive medicine -- two sides of the same
      token].
AB  - The topic of assisted reproductive medicine (ART) illustrates the two-sidedness
      of all medical advances. It encompasses not only a responsibility for research,
      but also a responsibility to research. Current discussion revolves around the
      central question whether an all too strict interpretation of the German
      'Embryonenschutzgesetz' (law to protect the embryo) with the resulting medical
      guidelines hinders the establishment of an ART practice corresponding to
      international standards. Current discussion, particularly in view of a new ART
      legislature in process, leaves the following topics open to debate: heterologous
      oocyte and sperm donations and a possible 'split' parenthood, the marital status
      of prospective couples and the serious clinical problem of multiple-gestation
      pregnancies. The technically feasible frequently surpasses what can or should
      ethically and legally be made possible.

PMID- 12499750
TI  - [The two elements air and water. Introduction to the main topic "water birth"].
AB  - Alternative birth methods such as deliveries 'under water' are part of a new
      concept of individualized obstetrics. Two recent studies from Austria and
      Switzerland confirm that water deliveries offer a safe and comfortable
      alternative to deliveries 'in bed' in low-risk pregnancies. The retrospective or
      prospective observational studies, however, are not randomized studies. Equal
      results can only be obtained if clear guidelines are worked out and strictly
      obeyed.

PMID- 12499751
TI  - [Water Birth: experience at a university clinic and a district hospital in
      Austria].
AB  - PURPOSE AND METHODS: In a retrospective case-control study, 265 water deliveries
      (with cephalic presentation) carried out at an Austrian university clinic and a
      district hospital were compared with a group of spontaneous births (without any
      surgical intervention) matched for age, gestational age and parity regarding the
      most important fetal and maternal obstetric parameters. RESULTS: 4.3% of all
      births at the university clinic and 13% of those at the district hospital took
      place in the water. Austrian women and women with a higher educational level were
      more numerous in this group. The duration of the different stages of birth was
      not essentially changed by the delivery in water. The cord blood pH of the water
      babies (median 7.29 and 7.35, respectively) was better than that of the control
      group (median 7.26), which may however be due to a positive selection of the
      women giving birth in the water. The number of episiotomies was markedly lower
      for water births (14 and 4%) than for land births (48%). In contrast, water
      births showed distinctly more first- and second-degree perineal tears (36 and
      41%) and labial tears (23 and 21%) than the control group (perineal 23%; labial
      7%). Women assigned to water birth needed fewer analgesics (8 and 9%) than the
      controls (64%). In puerperium, the haemoglobin values after water birth and after
      land birth did not differ. The infectious morbidity of the mother and child was
      not higher after water birth. CONCLUSIONS: Water birth is to be considered a safe
      method for a healthy mother and a healthy, full-term fetus with cephalic
      presentation (if the appropriate criteria are used at hospital wards with a
      specific infrastructure).

PMID- 12499752
TI  - [Experience with water births: a prospective longitudinal study of 9 years with
      almost 4,000 water births].
AB  - This prospective, longitudinal study spanning more than 9 years examines the
      influence of the birthing method, in particular water birth, on neonatal and
      maternal morbidity and mortality. Using questionnaires, maternal and neonatal
      data of 9,518 spontaneous singleton births with cephalic presentation, including
      3,617 water births and 5,901 land births, were compared. Land births show
      significantly higher rates of episiotomies as well as third- and fourth-degree
      perineal tears. Waters births show a significantly higher rate of births 'without
      injuries', first- and second-degree perineal tears, vaginal and labial tears. The
      average loss of blood after water birth is -5.26 g/l; this is statistically
      significantly less than after land births at -8.08 g/l. In 69.7%, water births
      required no analgesic, compared to 30.3% for land births. Water and land births
      do not differ with respect to maternal and neonatal infections. After land
      births, there was a significantly higher rate of newborn complications with
      subsequent transfer to an external NICU. There were neither maternal nor neonatal
      deaths related to the birthing event. Water births are just as safe as land
      births if obstetrical guidelines are followed. Risks, such as preeclampsia, signs
      of infection, meconium-stained amniotic fluid and pathological CTG, are found
      more frequently in land births and indicate that a safe and prospective birth
      management is being followed.

PMID- 12499753
TI  - [Pros and cons of water birth].
AB  - Women choose more and more often to deliver in water and expect the hospital to
      offer this method of giving birth. If we critically look at the data in the
      literature, we can conclude that it is safe to offer water delivery to any woman
      who belongs to a low-risk population. However, we have to add that no prospective
      randomized studies on this topic have been published so far. Thus, women may
      deliver in water if they wish, but the professionals working in the delivery room
      have to follow the guidelines and the usual safety standards of the particular
      clinic in order to avoid any unnecessary risks.

PMID- 12499754
TI  - [Is there a place for tubal ligation in modern contraception?].
AB  - About 30% of women with completed family planning choose tubal ligation as a
      method of contraception. Contraceptive safety of tubal ligation, with a Pearl
      index of 0.18, is comparable to those of OC or modern intrauterine devices (IUD).
      Pregnancies that occur after tubal ligation are often ectopic, especially in
      young women. There is currently no evidence that tubal ligation causes menstrual
      abnormalities. The risk of breast cancer, cancer of the endometrium or cervix is
      not elevated after tubal ligation, whereas the risk of ovarian cancer is even
      reduced. The risk of post-sterilization regret is higher when the operation was
      performed in women with children aged younger than 30 years. Tubal ligation is
      recommendable for women over 35 years of age with completed family planning,
      especially if contraindications for the use of OC or IUD exist. In general,
      vasectomy should always be discussed as a possible alternative.

PMID- 12499755
TI  - Infrared thermography in newborns: the first hour after birth.
AB  - OBJECTIVE: It was the aim of this study to investigate the surface temperature in
      newborns within the first hour after delivery. Furthermore, the influence of
      different environmental conditions with regard to surface temperature was
      documented. METHODS: Body surface temperature was recorded under several
      environmental conditions by use of infrared thermography. 42 newborns, all
      delivered at term and with weight appropriate for date, were investigated under
      controlled conditions. RESULTS: The surface temperature immediately after birth
      shows a uniform picture of the whole body; however, it is significantly lower
      than the core temperature. Soon after birth, peripheral sites become cooler
      whereas a constant temperature is maintained at the trunk. Bathing in warm water
      again leads to a more even temperature profile. Radiant heaters and skin-to-skin
      contact with the mother are both effective methods to prevent heat loss in
      neonates. CONCLUSIONS: Infrared thermography is a simple and reliable tool for
      the measurement of skin temperature profiles in neonates. Without the need of
      direct skin contact, it may be helpful for optimizing environmental conditions at
      delivery suites and neonatal intensive-care units.

PMID- 12499756
TI  - [Primary hyperparathyroidism with persistent hypercalcemia in pregnancy].
AB  - Parathyroidectomy is effective in avoiding complications of primary
      hyperparathyroidism (pHPT) during pregnancy, because in about 90% of cases, it is
      caused by parathyroid adenomas. We present a case of severe pHPT during pregnancy
      of unknown etiology and without detectable parathyroid adenoma so that surgery
      was not a therapeutic option. The patient was a 29-year-old gravida 1 who
      presented with pHPT at 11 weeks of gestation. Although her serum calcium levels
      were elevated throughout pregnancy (>3.05 mmol/l; reference range: 2.05-2.65), a
      vigorous premature infant was delivered at 35 weeks of gestation. The infant
      received calcium intravenously, vitamin D(3) orally and was fed with raw human
      milk (low phosphorus) to prevent hypocalcemia. The baby did not develop clinical
      signs of hypocalcemia. Her initial parathyroid hormone level was suppressed (1.1
      pg/ml; reference range: 15-65) and was normal at the age of 8 weeks. She was
      discharged from hospital at 14 days of life. Her physical, cognitive and motor
      development was normal through infancy and early childhood. In conclusion, pHPT
      during pregnancy does not necessarily lead to fetal or neonatal morbidity or
      mortality.

PMID- 12499757
TI  - Adnexal torsion during pregnancy -- management and literature overview.
AB  - We present a patient in the 30th week of gestation with adnexal torsion, which
      was treated by laparotomy with oophorectomy. After 2 days, we had to perform a
      cesarean section because of bowel obstruction. We discuss the diagnosis and
      treatment of adnexal torsion in pregnancy and compare laparoscopic management
      with laparotomy. By reviewing the literature, we evaluate the conservative
      therapy by detorsion employing Doppler sonography.

PMID- 12499759
TI  - The visible ear: a digital image library of the temporal bone.
AB  - High-fidelity computer-based modeling, simulation and visualization systems for
      the study of temporal bone anatomy and training for middle ear surgery are based
      on a sequence of digital anatomical images, which must cover a large tissue
      volume and yet display details in high resolution and with high fidelity.
      However, the use of existing image libraries by independent developers of virtual
      models of the ear is limited by copyright protection and low image resolution. A
      fresh frozen human temporal bone was CT-scanned and serially sectioned at 25
      microm and digital images of the block surface were recorded at 50- to 100-microm
      increments with a Light Phase(TM) single-shot camera back attachment. A total of
      605 images were recorded in 24-bit RGB resolution. After color correction and
      elimination of image size variation by differential cropping to 15.4 cm x 9.7 cm,
      all images were resampled to 3,078 x 1,942 pixels at a final resolution of 50
      microm/pixel and stored as 605 one-Mb JPEG files together with a three
      dimensional viewer. The resulting complete set of image data provides: (1) a
      source material suitable for generating computer models of the human ear; (2) a
      resource of high-quality digital images of anatomical cross sections from the
      human ear, and (3) a PC-based viewer of the temporal bone in three perpendicular
      planes of section.

PMID- 12499760
TI  - Meningitis following cochlear implantation: pathomechanisms, clinical symptoms,
      conservative and surgical treatments.
AB  - Pneumococcal otogenic meningitis is a rare postsurgical complication that can
      develop following stapedectomy or after cochlear implantation. The bacterial
      infection can be fatal in some instances. A recent increase in the incidence of
      otogenic meningitis among cochlear implant wearers is of concern. The majority of
      meningitis cases are associated with a 2-component electrode manufactured by one
      cochlear implant company. The device with the added 'positioner' component has
      been withdrawn from the market (FDA Public Health Web Notification: Cochlear
      Implant Recipients may be at Greater Risk for Meningitis, Updated: August 29,
      2002, www.fda.gov/cdrh/safety/cochlear.html). Not all cases have been subsequent
      to otitis media and symptoms have developed from less than 24 h up to a few years
      after implantation. The purpose of this paper is to review and discuss the
      pathogenesis, pathology/bacteriology and to elaborate on some clinical features
      of otogenic meningitis in implanted children and adults. Essential aspects of
      surgery, electrode design, and cochleostomy seal are discussed. Conclusions are
      drawn from the available data and recommendations are made for good practice in
      cochlear implantation and follow-up.

PMID- 12499761
TI  - Ante mortem ruptures of the endolymphatic membranes in children: real finding or
      artifact?
AB  - We undertook this study to determine whether or not ante mortem ruptures of the
      endolymphatic membranes occurred naturally in the infantile labyrinth, what were
      the most frequent locations and to assess the statistical correlation of an
      earlier finding of bulging of Reissner's membrane in pediatric temporal bones. We
      examined 128 temporal bones from 80 children between the ages of newborn to 12
      years with an average age of 15.4 months. All temporal bones were prepared by the
      celloidin technique and studied by light microscopy. The endolymphatic membranes
      of the cochlear duct, saccule, utricle and semicircular ducts were examined for
      ruptures. A rupture of the saccule and utricle was considered to be an ante
      mortem event if its edges were rolled and bound with fine adhesions and could be
      identified in adjacent sections. Ante mortem ruptures were seen in 11.1% of the
      specimens and occurred in 2.4% in Reissner's membrane, in 6.3% in the saccular
      membrane and in 2.4% in the utricular membrane. In these specimens, the
      histopathological changes included atrophy of the stria vascularis and collapse
      of the organ of Corti, which provided further evidence of an ante mortem event.
      Infants with extralabyrinthine congenital anomalies or children who were treated
      with chemotherapy were more likely to develop ruptures of the endolymphatic
      membranes if they also received aminoglycosides.

PMID- 12499762
TI  - Results of singular neurectomy in the posterior ampullary recess.
AB  - OBJECTIVE: To determine the effect on hearing and balance symptoms following
      singular neurectomy (SN) for benign paroxysmal positional vertigo (BPPV) in the
      ampullary recess of the posterior semicircular canal. RESEARCH DESIGN: The charts
      of 242 patients with chronic disabling BPPV who were treated with SN over a 29
      year period (1972-2001) were reviewed. The results on relief of BPPV and hearing
      function were recorded. A subset of 16 patients where the posterior ampullary
      recess was entered to expose the SN is described in detail with regard to an
      effect on hearing and balance. RESULTS: A total of 252 SN were performed in 242
      patients. Ten patients underwent bilateral SN sequentially; the remaining 232
      patients had unilateral SN. The ages of the patients ranged from 21 to 86 years,
      with a mean at 57 years. The female:male ratio was 174:68. Complete relief of
      BPPV was achieved in 244 patients (96.8%), incomplete relief in 3 (1%), and no
      relief in 5 (2%). Sensorineural hearing loss (SNHL) occurred in 9 patients
      (3.7%). A subset of 16 patients in whom the ampullary recess was opened during SN
      ranged in age from 21 to 79 years, with a mean at 56 years. The female:male ratio
      was 12:4, with right and left sides divided almost equally. Relief of BPPV was
      achieved in all 16 patients with no loss of hearing function. Five patients
      complained of a fistula response postoperatively (31%). The fistula response
      resolved by 6 months postoperatively in all 5 patients. CONCLUSIONS: SN is
      effective in relief of BPPV with little risk of SNHL (3.7%). The risk of SNHL is
      not increased when the posterior ampullary recess must be entered in order to
      transect the singular nerve. A positive fistula response may be present
      temporarily in almost one third of these patients.

PMID- 12499763
TI  - The suprameatal approach in cochlear implant surgery: our experience with 80
      patients.
AB  - The suprameatal approach (SMA) was first performed in 1999. It was developed for
      cochlear implantation as an alternative to the classic technique of transmastoid
      posterior tympanotomy approach. In the course of SMA the middle ear is exposed
      from the external auditory canal and the electrodes are inserted into the cochlea
      through a suprameatal tunnel bypassing the mastoid cavity. The goal of developing
      the SMA was to simplify the surgical technique, shorten the duration of surgery,
      enable wide exposure of the middle ear during the procedure, and avoid possible
      damage to the facial nerve and chorda tympani. We report here the results of 80
      patients who were operated on using the SMA technique.

PMID- 12499764
TI  - Veria operation updated. I. The trans-canal wall cochlear implantation.
AB  - The Veria operation is a non-mastoidectomy technique for cochlear implantation.
      It uses the transcanal approach to the middle ear and the cochlea. The steps of
      the procedure are: (1) endaural approach, that offers a wide accessibility to the
      middle ear structures; (2) inspection of the middle ear anatomy; (3)
      straightening of the postero-superior bony canal wall, which is usually concave;
      (4) performing the cochleostomy through the outer ear canal; (5) drilling of the
      suprameatal hollow, which is used for the accommodation of the electrode excess;
      (6) drilling of the trans-wall direct tunnel, which is the pathway for the active
      electrode; (7) alignment of the direct tunnel to the cochleostomy; (8) extension
      of the incision and preparing of the flaps; (9) creating of the bed and fixing
      the device; (10) insertion of the electrodes; (11) manipulating the excess of the
      active electrode, and (12) closing. For this technique, two special instruments
      have been developed: a special perforator used for the drilling of the direct
      tunnel for the active electrode, making it completely safe, and a safety
      electrode forceps used to manipulate the active electrode during insertion. The
      direct tunnel can be enlarged superiorly permitting insertion of two electrodes,
      in cases where a double electrode array implant has to be used. The method is an
      efficient tool for handling all cochlear implant cases, including difficult ones
      such as revision cases, malformations, cochlear ossifications and poor mastoid
      development. It is safe without complications in over a hundred cases and easy to
      learn.

PMID- 12499765
TI  - Veria Operation. II. Surgical results from 101 cases.
AB  - The 'Veria operation' is a new technique for cochlear implantation. It is a non
      mastoidectomy technique and uses the endaural approach for the cochleostomy and a
      direct tunnel drilled through the supero-posterior bony canal wall for the
      electrode. Two special instruments have been developed for this technique: a
      special perforator for the drilling of the direct tunnel and a safety electrode
      forceps for the insertion of the electrode. The method has been used in 101 cases
      with an age range from 2.5 to 75 years. 78 of them were primary operations and 23
      revision cases. From the revisions, 18 were surgical failures and 5 were device
      failures. There were two complications: in 1 case there was a thick skin flap,
      which was corrected under local anesthesia, and in 1 malformation case there was
      a retrograde insertion to the vestibule and the posterior semicircular canal,
      corrected 6 weeks later. The analysis of the results shows that this method has
      certain advantages, which are: it is simple and therefore the learning curve is
      fast; it is safe for the facial nerve, as the drilling is precisely controlled by
      the special perforator; it produces minimal bone trauma and due to fast healing,
      it permits early fitting a few days after operation; it is suitable for the
      difficult and revision cases and it can be used for very small children where the
      mastoid may have not been yet sufficiently developed.

PMID- 12499766
TI  - Three-dimensional eye rotation axis analysis of benign paroxysmal positioning
      nystagmus.
AB  - We have developed a new technique for analyzing the rotation vector of eye
      movement with an infrared CCD camera [Imai et al.: Acta Otolaryngol 1999;119:24
      28]. We used this technique to analyze the eye rotation axis of benign paroxysmal
      positioning nystagmus (BPPN) that was induced by the Dix-Hallpike maneuver in 14
      patients with benign paroxysmal positioning vertigo (BPPV). Eye rotation axes of
      BPPN in 8 patients were closely perpendicular to the posterior canal of the
      undermost ear in the provocative head position. Under the hypothesis that BPPN is
      due to a mechanical stimulation of the posterior canal by canalolithiasis, this
      finding suggested that the posterior canal of the undermost ear is the lesion. On
      the other hand, eye rotation axes of BPPN in the other 6 patients were closely
      aligned with the naso-occipital axis. It is suggested that canalolithiasis
      induces endolymphatic flow in both posterior and anterior canals via the common
      crus and the summation of the eye movements induced by stimulation of both the
      posterior and anterior canals rotates the eye along the naso-occipital axis.

PMID- 12499767
TI  - Vestibular evoked myogenic potentials in ipsilateral delayed endolymphatic
      hydrops.
AB  - We recorded vestibular evoked myogenic potentials (VEMPs) in 12 patients
      diagnosed as having ipsilateral delayed endolymphatic hydrops (DEH). Seventy-five
      percent (9/12) of the patients showed decreased or absent VEMPs in the affected
      ears. Almost all patients had normal VEMPs in the unaffected ears. In addition,
      in 4 patients, VEMPs were recorded before and 3 h after oral glycerol
      administration (1.3 g/kg body weight). VEMPs improved after glycerol
      administration in 2 of the 3 patients whose VEMPs had been abnormal in the
      affected ears before glycerol administration. None of the 4 patients presented
      significant changes in VEMPs in the unaffected ears after glycerol
      administration. Improvement of VEMPs after glycerol administration confirmed the
      existence of endolymphatic hydrops in patients with ipsilateral DEH. In
      conclusion, VEMPs are useful to evaluate the function of otolith organs in
      patients with ipsilateral DEH, and the glycerol test using VEMPs may be useful to
      detect endolymphatic hydrops in ipsilateral DEH.

PMID- 12499768
TI  - Reconstruction of the stapes superstructure with a combined glass-ceramic
      (Bioverit) implant in guinea pigs.
AB  - BACKGROUND: Reconstruction of the stapes superstructure continues to be a problem
      for otologists. Optimal fixation of implants on the stapes footplate has not yet
      been achieved. METHODS: We postulated that bony fixation, between implant and
      stapes, could be confined exclusively to the footplate region by modifying the
      bioactivity of the implant material. Therefore, after removal of the
      superstructure in guinea pigs a combined biovitro ceramic implant (Bioverit I and
      Bioverit II) was placed on the stapes footplate in 10 guinea pigs. As a control,
      we employed a group of 6 animals in which the stapes superstructure was removed
      without placing any implant. RESULTS: After 25 weeks the implants were found to
      be dislocated laterally. We observed fixation with the wall of the middle ear. In
      the control group we also found new bone formation and even a bow shaped
      regeneration of the stapes superstructure. CONCLUSION: Combined Bioverit
      stapedial implants were found to routinely fix to the middle ear wall of the
      guinea pig. The guinea pigs' enormous potential for bone regeneration in the
      middle ear ossicular chain make this species unsuitable for exploring hypotheses
      on human middle ear reconstruction.

PMID- 12499769
TI  - Blood group in otitis media with effusion.
AB  - The aim of the present study was to assess whether blood group ABO is a risk
      factor for otitis media with effusion (OME). In a screening program 889 children
      were studied with pneumatic otoscopy, tuning fork tests, audiometry, impedance
      measures and blood group tests. Among these children, there were 51 children with
      OME at the time of examination (5.7%), and 838 healthy children. Multivariate
      logistic regression risk for OME was compared between children with different
      blood groups, taking sociodemographic and history-related risk factors into
      account. Blood group and OME were found to be statistically related. Considering
      children of blood group A as a reference, children with blood group O had a
      statistically significant lower risk of OME. Children with blood group B did not
      have lower risk. Children with blood group AB had lower relative risk for OME,
      but not significantly so. Examining Rhesus factor as a predictor for OME, no
      relationship was found. It is concluded that blood group O (and possibly AB)
      plays a preventive role, while blood group A or B are burdensome for OME.

PMID- 12499770
TI  - Psychometric normalization of a hyperacusis questionnaire.
AB  - Clinical hyperacusis consists of a marked intolerance to ordinary environmental
      sounds, while hearing thresholds are quite often normal. Hyperacusis appears to
      be a subjective phenomenon, which is not easily defined or quantified by
      objective measurements. In order to create a tool suitable to quantify and
      evaluate various hyperacusis symptoms, a questionnaire screening several aspects
      of auditory symptomatology has been constructed. Two hundred and one subjects
      (who were either hyperacusic or not), randomly selected from the general
      population, were tested. A principal component analysis performed on the
      correlation matrix of the 14 items of the questionnaire isolated three
      dimensions: attentional, social, and emotional. The three dimensions had
      satisfactory internal consistency reliability. The mean +/- SD total score was 15
      +/- 6.7 out of 42 (maximum of hyperacusis) and a score greater than 28 seems to
      represent a strong auditory hypersensitivity. This new psychometric tool should
      further be tested on hyperacusic patients to verify its relevance in pathology
      and define the involvement of the three dimensions statistically obtained on the
      hyperacusis symptomatology.

PMID- 12499771
TI  - Ostiomeatal complex in normal Semitic adults.
AB  - This is a clinicoradiological study of six components in the ostiomeatal complex
      (OMC) of normal adult Saudis of both sexes. It presents them through the mean
      values of the osseous components of the computed tomographic coronal cuts of the
      nose and paranasal sinuses. The maximum mean value of the maxillary ostium in
      males and females was 0.22 and 0.21 cm, respectively. The maximum height of the
      uncinate process was 1.27 and 1.26 cm, the largest surface area of bulla
      ethmoidalis was 0.69 and 0.52 cm(2), the maximum width of the infundibulum was
      0.22 and 0.21 cm, the largest width of the middle tubinate was 1.47 and 1.44 cm
      and the maximum width of the middle meatus was 0.83 and 0.79 cm, respectively.
      Their standard deviation and p value were calculated. The measured units of OMC
      did not show any significant variation between the two sexes as well as between
      the different age groups except for the bulla ethmoidalis where there was
      significant variation between males and females in the age group of 15-31 years.
      This study was done to provide endoscopic rhinologists a set of reference
      distances of OMC.

PMID- 12499772
TI  - Lipoadenoma: is it arising from thyroid or parathyroid? A diagnostic dilemma.
AB  - Fat-containing lesions of endocrine organs are rare. Distinguishing lipoadenomas
      of the thyroid gland from lipoadenomas of parathyroid glands can be challenging
      during intraoperative consultation. Our patient had a well-circumscribed tan-pink
      nodule present on the surface of the thyroid gland, exhibiting abundant fat
      interspersed between the cells, with ample eosinophilic cytoplasm arranged in
      trabeculae and solid sheets. Immunohistochemistry showed strong positivity for
      thyroglobulin confirming the origin of the nodule to be thyroid. Only few cases
      of lipoadenomas of the thyroid and parathyroid have been reported in the
      literature. There is considerable histologic overlap between the two, making it
      difficult to determine the site of origin. We briefly discuss the features that
      may be helpful in this distinction.

PMID- 12499773
TI  - Magnetic resonance imaging and high-resolution computed tomography in the
      otospongiotic phase of otosclerosis.
AB  - Otosclerosis very often leads to severe hearing loss in a chronic progressive
      manner. In the first phase of the disease, otospongiosis causes an inflammatory
      osteolytic process in the osseous labyrinthine capsule. In the cases reported
      here, this osteolytic process was pronounced in the osseous capsule of the
      cochlea. High-resolution CT and MRI showed the precise localization and stage of
      this inflammatory-osteolytic process in the petrous bone, while scintigraphy
      confirmed the diagnosis.

PMID- 12499774
TI  - Olfactory neuroblastoma. A report of 3 cases.
AB  - Olfactory neuroblastoma is a rare malignant tumour, usually diagnosed at advanced
      stages. We studied 3 patients who were treated at our Institute between 1991 and
      1999. One patient presented with a stage A and 2 with a stage B tumour. One
      patient presented with coma due to inappropriate secretion of antidiuretic
      hormone associated with a stage B tumour. All 3 patients were treated with
      complete surgical resection via a lateral rhinotomy approach and postoperative
      radiotherapy. There was no involvement of the cribriform plate. One patient
      developed a metachronous regional metastasis and was treated with neck dissection
      and radiotherapy. All 3 patients are free from recurrence with a follow-up period
      of 9 years, 18 months and 1 year, respectively. Combination therapy is the
      cornerstone of treatment for olfactory neuroblastoma. Complete surgical resection
      is the most important prognostic factor and can be accomplished via lateral
      rhinotomy for early stage tumours.

PMID- 12499775
TI  - The leukocyte antigen CD43 is expressed in different cell lines of
      nonhematopoietic origin.
AB  - CD43 is an abundant transmembrane sialoglycoprotein in leukocyte-type cell lines,
      but it has also been suggested to be present in colon adenomas and colon
      carcinomas. We have now shown that CD43 is expressed in a variety of cell lines
      of different origins (CaSKI, A549, 293, MTSV1-7, MCF7, HT-1080, Jurkat, K562,
      COLO 205, HT-29, Caco-2, DLD-1 and SW480). The level of expression of CD43 mRNA
      was analyzed by reverse transcriptase-polymerase chain reaction and that of the
      protein by immunoprecipitation and Western blot, flow cytometry and confocal
      microscopy using two monoclonal anti-CD43 antibodies (L10 and 4D2). As all cell
      lines expressed CD43, it is suggested that CD43 has a more fundamental function
      than previously believed and thus cannot be considered only as a specific
      leukocyte marker.

PMID- 12499776
TI  - The enzymatic basis for the conversion of nonfucosylated to fucosylated alpha
      fetoprotein by acyclic retinoid treatment in human hepatoma cells: activation of
      alpha1-6 fucosyltransferase.
AB  - The purpose of the present study was to investigate the mechanism by which
      nonfucosylated alpha-fetoprotein (AFP) is converted to fucosylated AFP in human
      hepatoma cell lines exposed to acyclic retinoid (AR), an effective drug for the
      secondary prevention of hepatocellular carcinoma. AR treatment (100 microM) of
      HepG2 and Hep3B cells significantly increased the activity and mRNA levels of
      alpha1-6 fucosyltransferase (alpha1-6 FucT), the enzyme responsible for the
      fucosylation of AFP, leading to an increase in fucosylated glycoproteins as
      evidenced by lectin binding measurements. Lectin immunoelectrophoresis of AFP
      obtained from culture media indicated that the relative percentage of
      nonfucosylated AFP (L1 fraction) was decreased and alpha1-6 fucosylated AFP (L3
      fraction) was increased in these hepatoma cell lines after treatment with AR. The
      total AFP levels were, however, markedly suppressed by AR treatment, and
      therefore the absolute L3 fraction on the basis of the total AFP present was
      extremely low. These results demonstrate that AR enhances the conversion of the
      L1 to the L3 fraction due to the activation of alpha1-6 FucT in human hepatoma
      cell lines despite clinical outcome with AR treatment and the L3 fraction of AFP.
      Even though the dramatic decrease in AFP is the limiting factor in the synthesis
      of the L3 fraction and, therefore, the absolute value of fucosylated AFP is
      extremely low, the conversion from L1 to L3 as judged by lectin
      immunoelectrophoresis represents a good marker for the progress of AR treatment.

PMID- 12499777
TI  - Detection of mammaglobin in the sera of patients with breast cancer.
AB  - Current procedures for the diagnosis of breast cancer are cumbersome and
      invasive, making detection of this disease difficult. A rapid screening test for
      early detection of breast cancer would allow for better management of this deadly
      disease. In this report, we show that, with the exception of the skin,
      mammaglobin mRNA is specifically expressed in mammary tissue and commonly
      overexpressed in breast cancer. Mammaglobin is not expressed in other types of
      cancer including colon, lung, ovarian, and prostate cancer. Breast-specific
      expression of mammaglobin protein was shown using immunohistochemical methods.
      Mammaglobin is secreted from both established breast cancer cell lines and
      primary breast carcinoma cells cultured in vitro. Using a monoclonal antibody
      based assay for monitoring the presence of mammaglobin in serum, elevated levels
      of mammaglobin were detected in sera of patients with breast cancer, but not in
      healthy women. Thus, mammaglobin, which is overexpressed and secreted from breast
      carcinoma cells, is detectable in sera of patients with breast cancer and may
      provide a rapid screening test for the diagnosis and management of breast cancer.

PMID- 12499778
TI  - Low levels of endostatin in the urine from patients with malignant disease.
AB  - Endostatin, a C-terminal subfragment of collagen XVIII, and angiostatin, a family
      of fragments originating from the NH(2)-terminal portion of plasminogen, have
      been described as potent inhibitors of angiogenesis and malignant growth. We have
      earlier reported the presence of angiostatin fragments in urine from cancer
      patients. In this study, we investigated the occurrence of endostatin and the
      correlation between the amounts of endostatin and angiostatin in urine collected
      from 104 patients with different types of malignancies and in 16 controls. The
      amounts of endostatin were measured with a commercial immunoassay. Angiostatin
      fragments were quantitated by Western blot analysis. Only small amounts of
      endostatin were observed, both in patients and controls, and there was no
      significant difference in the amount of endostatin between the patients and the
      controls. Both endostatin and angiostatin concentrations in the urine showed a
      strong dependence on impaired kidney function, especially tubulus function,
      measured as the amount of urine alpha(1)-microglobulin. Interestingly, there was
      no significant correlation between endostatin and angiostatin concentrations in
      the patients with impaired kidney function (elevated urine albumin or urine
      alpha(1)-microglobulin), suggesting a possible difference in circulating
      concentrations of these inhibitors.

PMID- 12499779
TI  - Monoclonal antibodies against tissue-nonspecific alkaline phosphatase. Report of
      the ISOBM TD9 workshop.
AB  - Nineteen monoclonal antibodies (MAbs) against tissue-nonspecific
      (liver/bone/kidney) alkaline phosphatase (TNALP) were investigated in the ISOBM
      TD-9 Workshop. These MAbs were generated with antigens obtained from human bone
      tissue (n = 9), human osteosarcoma cell lines (SaOS-2 and TPX; n = 7) and human
      liver tissue (n = 3). The evaluation included the following antigen forms: (a)
      commercially available preparations of human bone ALP (BALP) and liver ALP
      (LALP); (b) human BALP isoforms, B/I, B1 and B2; and (c) soluble secreted epitope
      tagged recombinant human TNALP (setTNALP) expressed in COS-1, osteosarcoma (SaOS
      2) and hepatoma (Huh2) cell lines. In addition, 16 TNALP mutant cDNAs
      corresponding to a wide spectrum of reported hypophosphatasia mutations were used
      in an attempt to map specific immunoreactive epitopes on the surface of the TNALP
      molecule. The TD-9 MAbs were evaluated by immunoradiometric (IRMA) assays, cross
      inhibition and different enzyme immunoassay designs. No indications of explicit
      tissue discriminatory immunoreactivities of the investigated MAbs against TNALP
      were found. However, certain IRMA combinations of MAbs increased the specificity
      of BALP measurements. All MAbs bound to the three BALP isoforms B/I, B1 and B2,
      but none of the investigated MAbs were specific for any of the isoforms.
      Significant differences were, however, found in immunoreactivity between these
      isoforms, with cross-reactivities ranging from 21 to 109% between the two major
      BALP isoforms B1 and B2. Desialylation with neuraminidase significantly increased
      the MAb affinity for the BALP isoforms B/I, B1 and B2, and also decreased the
      observed differences in cross-reactivity between these isoforms. We suggest,
      therefore, that the MAb affinity is dependent on the amount/number of terminal
      sialic acid residues located at the five putative N-glycosylation sites. Based on
      the overall results, we present a putative three-dimensional model of the TNALP
      molecule with positioning of the four major antigenic domains (designated A-D) of
      the investigated MAbs. The TNALP molecule is depicted as a homodimer, hence most,
      but not necessarily all, epitopes are displayed twice. The antigenic domains were
      positioned with the following assumptions: domain A was positioned close to the
      active site since most of these MAbs interfered with the catalytic activity.
      Interestingly, both MAbs included in the commercial BALP kits were grouped with
      domain A. Moreover, 4 of the 5 putative N-glycosylation sites (with terminal
      sialic acid residues) are located within, or with close proximity to, domain A.
      Domain B was localized at the top flexible loop (crown domain) of the TNALP
      molecule. Domain C was clearly defined by the IRMA assay combinations and by site
      directed mutants of TNALP to be close to residue E281, which is located near the
      fourth metal binding site, likely to be occupied by a calcium ion. Domain D was
      positioned close to residues A115, A162 and E174, but this domain was also close
      to the GPI anchor site. In conclusion, none of the 19 investigated TD-9 MAbs were
      entirely specific for BALP or LALP, thus indicating that all MAbs bind mainly to
      epitopes on the common protein core of BALP and LALP and/or common glycosylated
      epitopes. However, some MAbs (either single or in combination with other MAbs)
      work sufficiently well to measure BALP when the assayed samples do not contain
      elevated levels of LALP.

PMID- 12499780
TI  - Protein epitopes in carcinoembryonic antigen. Report of the ISOBM TD8 workshop.
AB  - To characterize antigenic sites in carcinoembryonic antigen (CEA) further and to
      investigate whether there are differences between colon tumor CEA and meconium
      CEA (NCA-2) that can be detected by anti-CEA monoclonal antibodies (MAb), 19 new
      anti-CEA MAb were analyzed with respect to specificity, epitope reactivity and
      affinity. Their reactivities were compared with 10 anti-CEA MAb with known CEA
      domain binding specificity that have previously been classified into five
      nonoverlapping epitope groups, GOLD 1-5. Cross-inhibition assays with antigen
      coated microtiter plates and immunoradiometric assays were performed in almost
      all combinations of MAbs, using conventionally purified CEA (domain structure: N
      A1B1-A2B2-A3B3-C) from liver metastasis of colorectal carcinomas, recombinant
      CEA, meconium CEA (NCA-2), truncated forms of CEA and NCA (CEACAM6) as the
      antigens. The affinity of the MAbs for CEA was also determined. The new MAbs were
      generally of high affinity and suitable for immunoassays. Three new MAbs were
      assigned to GOLD epitope group 5 (N-domain binding), 3 MAbs to group 4 (A1B1
      domain), 1 to group 3 (A3B3 domain), 3 to group 2 (A2B2 domain) and 3 to group 1
      (also the A3B3 domain). Three MAbs formed a separate group related to group 4,
      they were classified as GOLD 4' (A1B1 domain binding). The remaining 3 MAbs
      appear to represent new subspecificities with some relationship to GOLD groups 1,
      2 or 4, respectively. Five MAbs, all belonging to epitope group 1 and 3, reacted
      strongly with tumor CEA but only weakly or not at all with meconium CEA,
      demonstrating that the two products of the CEA gene differ from each other,
      probably due to different posttranslational modifications.

PMID- 12499781
TI  - [Isolation and culture of pig hepatocyte in large scale for the application of
      bioartificial liver system].
AB  - BACKGROUND/AIMS: Acute hepatic failure is a serious problem. Its mortality
      reaches up to 80%. Only liver transplantation has been accepted as a definite
      treatment for patients with hepatic failure but shortage of donor organs is the
      main obstacle of this approach. A possible solution to this problem is a
      bioartificial liver system, perfusion of patients blood to isolated hepatocyte.
      In this study, we performed the isolation and culture of pig hepatocyte in large
      scale for the application of bioartificial liver system. METHODS: Hepatocyte
      isolation was performed by two-step collagenase method via portal vein perfusion
      in 10 kg female pigs. After that, we compared the functional differences of the
      spheroid culture to the monolayer culture of hepatocyte. The viability and the
      function of hepatocyte were assessed using trypan-blue exclusion test and the
      measurement of the rate of ureagenesis and ammonia removal. RESULTS: The average
      viability and yield of hepatocyte were 86.8 +/- 8.0 % and 7.8 +/- 5.4 X 10(9),
      respectively. The spheroid culture was superior to the monolayer culture in
      functional aspect of hepatocyte, and their differences, especially for ammonia
      removal, were more apparent in parallel with culture time. CONCLUSIONS: For
      hepatocyte isolation, we obtained sufficient viability and yield of hepatocyte
      for clinical usage of bioartificial liver system. The function of hepatocyte
      seems to be better in the spheroid culture than in the monolayer culture. Further
      studies are needed for application of bioartificial liver system in clinical
      setting.

PMID- 12499782
TI  - [Five-year follow-up of clinical and laboratory data of early liver cirrhosis
      patients confirmed by liver biopsy].
AB  - BACKGROUND/AIMS: It is important to evaluate the general status of the liver
      including the structural and inflammatory aspects, as well as the functional
      aspects, in order to determine a patient's treatment modality and prognosis.
      METHODS: 55 Child-Pugh class A liver cirrhosis patients confirmed by liver biopsy
      have been categorized into 4 groups based on the shunt index and p-value(Y=
      3.3431-0.8160 ALT/AST ratio-0.0343 X prothrombin time+2.6963 X shunt index, p =
      e(y)/(e(y)+1)), which was obtained by Thallium- 201 scan; group I - shunt index
      less than 0.3 and p-value less than 0.7; group II - shunt index less than 0.3 and
      p-value more than 0.7; group III - shunt index more than 0.3 and p-value less
      than 0.7; and group IV - shunt index more than 0.3 and p-value more than 0.7.
      Statistical analyses used were ANOVA, paired t-test, and Chi-square test.
      RESULTS: 1. The laboratory data after a 5-year follow-up also showed a
      significant difference between four groups. 2. In group IV, the Child-Pugh class
      after 5 years worsened, and complications of liver cirrhosis such as esophageal
      varix, ascites, and hepatic encephalopathy occurred more frequently. 3. In group
      II, the laboratory data after a 5-year follow-up indicated some improvement.
      CONCLUSION: It can be seen that even early in patients with initially the same
      cirrhosis, the course of the illness can progress to a variety of different
      situations. The measurement of shunt index and the p-value of cirrhosis will be
      more helpful in the follow-up evaluation and predicting its prognostic index in
      liver cirrhosis patients.

PMID- 12499783
TI  - [Comparison of Doppler ultrasonography and hepatic venous pressure gradient in
      assessing portal hypertension in liver cirrhosis].
AB  - BACKGROUND/AIMS: This prospective study aimed to determine if Doppler
      ultrasonography can be representative of hepatic venous pressure gradient (HVPG)
      in assessing the severity of portal hypertension and response to drug reducing
      portal pressure. METHODS: The HVPG and the parameters of Doppler ultrasonography
      including portal venous velocity (PVV) and splenic venous velocity, the
      pulsatility and resistive index of hepatic, splenic and renal arteries were
      measured in 105 patients with liver cirrhosis. In 31 patients the changes of
      hepatic venous pressure gradient and portal venous velocity after administration
      of terlipressin were evaluated. The patients who showed a reduction in HVPG of
      more than 20% of the baseline were defined as responders to terlipressin.
      RESULTS: Any Doppler ultrasonographic parameters did not correlate with HVPG.
      Both HVPG and PVV showed a highly significant reduction after the administration
      of terlipressin(-28.3 +/- 3.9%, -31.2 +/- 2.2% respectively). However, PVV
      decreased significantly not only in responders(31.7 +/- 2.4%) but also in
      nonresponders(29.5 +/- 6.1%). CONCLUSION: Doppler ultrasonography can not be
      representative of HVPG in assessing the severity of portal hypertension and
      response to drug reducing portal pressure in liver cirrhosis.

PMID- 12499784
TI  - [Prevalence and risk factors of significant intrapulmonary shunt in cirrhotic
      patients awaiting liver transplantation].
AB  - BACKGROUND/AIMS: Hepatopulmonary syndrome is a condition of severe hypoxia with
      intrapulmonary shunt (IPS) in the setting of hepatic dysfunction. Liver
      transplantation has been suggested as a definite treatment for hepatopulmonary
      syndrome with reversal of IPS in some patients. Inconsistency of response and
      inability to predict reversibility, however, are significant problems. We
      performed this study to evaluate the prevalence of significant IPS in
      pretransplantation cirrhotic patients and to find any risk factors of IPS.
      METHODS: Fifty-seven patients (M:F = 38:19, median age 49 years (range 18-71))
      with liver cirrhosis awaiting liver transplantation were serially included. Their
      IPS status was evaluated using contrast- enhanced echocardiography. Significant
      shunt was defined as a shunt of grade >or= 2. RESULTS: Significant IPS was
      detected in 30 (52.6%) among 57 patients. Significant shunt was found in 24
      (63.2%) of 38 Child-Pugh class C patients and in 6 (31.6%) of 19 Child-Pugh class
      A or B patients (p < 0.05). No significant difference in prevalence of
      significant shunt was seen according to age, sex, presence or absence of
      hepatocellular carcinoma, ascites, hepatic encephalopathy, and gastroesophageal
      varix. CONCLUSION: Significant intrapulmonary shunt is a common finding in
      cirrhotic patients awaiting liver transplantation. Child-Pugh class C is the risk
      factor associated with high prevalence of significant shunt.

PMID- 12499785
TI  - [Relationship of propranolol pharmacokinetic parameters with portosystemic shunt
      in CCl4-induced cirrhotic rats].
AB  - BACKGROUND/AIMS: This study was designed to determine the relationship of
      propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced
      cirrhotic rats. METHODS: Cirrhotic rats(n=6) were induced by intramuscular
      injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6)
      were injected intramuscularly with the same dose of olive oil for 12 weeks. We
      evaluated the amount of portosystemic shunt by thallium-201 per rectal
      scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats,
      the serum propranolol concentrations were analyzed by a HPLC-fluorimetric
      detector system. Pharmacokinetic parameters such as C0, AUC, t1/2(beta), and CLp
      were determined in each group. Then, a small amount of heptic tissue was obtained
      and subjected to determination of the hepatic collagen content by quantitating 4
      hydroxyproline and were inspected by microscope after hematoxylin and eosin
      stain. RESULTS: In liver biopsy, liver fibrosis progressed in CCl4-induced
      cirrhotic rats. The serum concentrations of propranolol were significantly (p <
      0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline,
      mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p
      < 0.01) higher than that in control rats. There was a relationship between AUC,
      H/L ratio, and amount of 4-hydroxyproline. CONCLUSION: H/L ratio may help in the
      selection of drug dosage (especially blood flow dependent drug) in pre-clinical
      studies for chronic liver disease during the drug development process.

PMID- 12499786
TI  - [Prospective randomized trial of intravenous ciprofloxacin for prevention of
      bacterial infection in cirrhotic patients with esophageal variceal bleeding].
AB  - BACKGROUND/AIMS: In cirrhotic patients with esophageal variceal bleeding,
      bacterial infections are a frequent complication. Oral antibiotic prophylaxis
      decreases the incidence of bacterial infections. The administration of oral
      antibiotics, however, may be difficult in some cirrhotic patients with active
      bleeding. The purpose of this study was to assess the efficacy of prophylactic
      intravenous antibiotics for the prevention of bacterial infections in cirrhotic
      patients with esophageal variceal bleeding. METHODS: From December 1998 to
      September 2001, a total of 40 consecutive cirrhotic patients with Child-Pugh
      class B or C were enrolled after emergent endoscopic esophageal variceal ligation
      (EVL) was taken because of esophageal variceal bleeding. Enrolled patients were
      randomized into a treatment group and a control group. The treatment group (n=20)
      received the intravenous ciprofloxacin 200mg IV q 12 hours for 3 days while the
      control group(n=20) didn,t. RESULTS: Bacterial infection developed in nine
      patients (45%) of the control group and only two patients (10%) in the treatment
      group. The incidence of bacterial infections was significantly lower in the
      treatment group than the control group (p < 0.005). The hospital cost and length
      of hospital stay decreased in the treatment group compared with the control group
      (p < 0.001). There were no differences in the hospital course and mortality
      within 30 days between the two groups. CONCLUSIONS: In cirrhotic patients with
      variceal bleeding and with Child-Pugh class B or C, the use of intravenous
      ciprofloxacin for 3 days after EVL was not only effective in the prevention of
      bacterial infections but also cost-effective.

PMID- 12499787
TI  - [Expression patterns of E-cadherin and beta-catenin according to
      clinicopathological characteristics of hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: E-cadherin is involved in intercellular binding and cellular
      polarity formation. beta-catenin plays a fundamental role in regulation of the E
      cadherin cell adhesion complex. The abnormalities of the components of the
      complex may disrupt this adhesive function. We investigated the expression
      patterns of E-cadherin and beta-catenin to determine the clinical significance of
      these proteins in hepatocellular carcinoma. MATERIALS/METHODS: Thirty-six
      hepaticellular carcinoma tissues and adjacent non-tumor specimens were analyzed.
      Subcellular distribution of E-cadherin and beta-catenin was examined by
      immunohistochemistry staining. We evaluated the patterns of the expression, and
      investigated the relationship with the cause of HCC; level of AFP; TNM stage;
      tumor size; growth types; metastasis; differentiation grade of HCC; and presence
      of portal vein thrombosis. RESULTS: Immunohistochemistry showed that all non
      tumor tissues had membranous type staining of E-cadherin. All non-tumor tissues
      showed cytoplasmic type staining of beta-catenin, but no beta-catenin
      accumulation in nuclei was found. 58% (21/36) of HCC showed positive expression
      of E-cadherin in cytoplasmic membrane. The cytoplasmic expression of beta-catenin
      in HCC was 83% (30/36); nuclear expression in 14% (5/36); and no staining in 3%
      (1/36). Nuclear beta-catenin expression was observed in none (0/4) of the well
      differentiated HCC; 17%(3/9) of moderate-differentiated HCC; and 17%(2/6) of
      poorly-differentiated HCC. There were no relationships between E-cadherin and
      beta-catenin expression with other clinicopathologic factors. CONCLUSIONS: Loss
      of cytoplasmic staining of E-cadherin and nuclear accumulation of beta-catenin
      were observed in HCC. Nuclear accumulation of beta-catenin was not found in well
      differentiated HCC but was found in poorly differentiated HCC.

PMID- 12499788
TI  - [Radiation therapy for bone metastasis from hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Recent advances in both diagnosis and treatment have markedly
      improved the prognosis in patients with hepatocellular carcinoma (HCC). Bone
      metastasis has become a clinical problem in the treatment of HCC patients. The
      purpose of this study was to evaluate the palliative effect of radiotherapy for
      painful bone metastasis from HCC. METHODS: From January 1991 to June 2000, 51
      patients (77 sites) with painful bone metastasis from HCC were retrospectively
      analyzed. Ages ranged from 21 to 80 years (median 55 years). The male:female
      ratio was 7.5:1. Synchronous or metachronous bone metastasis was seen in 20 (39%)
      and 31 patients (61%), respectively. The most common symptom of bone metastasis
      was pain (45 patients, 88%). Twenty-one patients (41%) had a solitary bone
      metastasis while 30 (59%) had multiple ones. The sites of bone metastasis, in
      order of frequency, were the vertebra (38), rib (20), and pelvis (19). The total
      radiation dose ranged from 12.5 to 50 Gy (median 30 Gy). The Wisconsin Brief Pain
      Questionnaire was used to evaluate pain response. RESULTS: The overall 1 and 2
      year survival rates from the time of bone metastasis were 15% and 4%,
      respectively. The median survival time was 5 months. Intrahepatic stage(p=0.014),
      and metastasis to other organs(p=0.019) were significant prognostic factor for
      survival by univariate analysis. There was, however, no independent prognostic
      factor on multivariate analysis. Pain relief after radiotherapy was achieved for
      56 sites (73%). CONCLUSION: The expected life span (median 5 months) in this
      group of patients suggests a strong necessity for effective treatment for
      symptomatic palliation. Radiation therapy was effective in pain palliation for
      bone metastasis from HCC, and this could improve patients' quality of life.

PMID- 12499789
TI  - [A case of acute hepatitis E].
AB  - Hepatitis E is an infectious viral disease with clinical and morphologic features
      of acute hepatitis. Although HEV infection is endemic in the Indian subcontinent,
      Southeast and Central Asia, a large outbreak of hepatitis E was identified in
      China. Smaller outbreaks have been observed in the Middle East, northern and
      western parts of Africa, and Mexico. Sporadic hepatitis E also has been observed
      in several countries. In nonendemic regions, the sporadic cases of hepatitis E
      are almost always associated with travel to HEV-endemic regions. In Korea, there
      has been no report on hepatitis E. Recently, we experienced a case of acute
      icteric hepatitis in which serologic study showed seroconversion of IgM anti-HEV.
      The patient did not have any travel history to an HEV-endemic area. We report
      this as an initial case of acute hepatitis E in Korea.

PMID- 12499790
TI  - [A case of acute cholestatic hepatitis associated with Orlistat].
AB  - Orlistat(Xenical(R), Roche) is considered a safe and effective drug to treat
      obesity by reduced absorption of 30% digested fat. To date, no serious adverse
      effects affecting the liver have been published except a case of subacute hepatic
      failure leading to liver transplantation in a young women with moderate obesity
      treated with orlistat. We report a case of acute cholestatic hepatitis in a young
      woman with moderate obesity treated with orlistat: a 33-year-old female admitted
      for the evaluation of jaundice. Abdominal ultrasonography, ERCP, routine
      chemistry, viral markers, and a fine needle biopsy of liver were performed.
      Microscopic findings of the liver biopsy specimen were compatible with acute
      cholestatic hepatitis. After steroid therapy, liver function was improved.

PMID- 12499791
TI  - [A case of idiopathic hypereosinophilic syndrome with hepatic involvement in a 5
      year-old boy].
AB  - Idiopathic hypereosinophilic syndrome is defined as the presence of prolonged
      eosinophilia without an identifiable underlying cause and with evidence of end
      organ dysfunction. The organs involved are the heart, bone marrow, nervous
      system, lungs, liver, skin, and gastrointestinal tract. Hepatic involvement is
      found in about 30% of patients of idiopathic hypereosinophilic syndrome. It
      occurs rarely in infants and children. In this report, we experienced one case of
      idiopathic hypereosinophilic syndrome with hepatic involvement in a 5-year-old
      boy who complained of intermittent fever and right upper quadrant abdominal pain.
      An abdominal ultrasound examination revealed an ill-defined low-echoic lesion in
      the liver. Pathologic findings of a biopsy specimen clearly showed the
      infiltration of eosinophils in the liver. Laboratory data disclosed absolute
      eosinophilia. There was no evidence of allergic disease or parasitic infestation.

PMID- 12499792
TI  - [A case of refractory hepatic hydrothorax that was not treated by transjugular
      intrahepatic portosystemic shunt].
AB  - Refractory hepatic hydrothorax has been treated by conservative methods: salt and
      water restriction, diuretics, thoracentesis, thoracostomy, and pleurodesis. The
      results, however, havebeen disappointing. Recently, TIPS has emerged as a new
      method for refractory hepatic hydrothorax, but it may lead to fatal
      complications. We report a case of refractory hepatic hydrothorax that was not
      treated by TIPS despite of successful control of ascitest.

PMID- 12499793
TI  - [A case of resection of biloma with hepatocellular carcinoma after embolization].
AB  - Intrahepatic biloma is one of the rare complications occurring after
      transcatheter arterial chemoembolization (TACE). Biloma after TACE may result
      from the development of peripheral bile duct necrosis caused by microvascular
      damage of the peribiliary capillary plexus, and intrahepatic ductal stenosis. We
      report a case of resection of intrahepatic biloma with hepatocellular carcinoma
      after TACE.

PMID- 12499794
TI  - [Biliary papillomatosis].

PMID- 12499795
TI  - [Spontaneous intrahepatic portosystemic shunt].

PMID- 12499796
TI  - [Ultrastructure of chronic liver diseases: hepatic fibrosis and stellate cells of
      the sinusoid].

PMID- 12499797
TI  - Oromucosal cytokine therapy: mechanism(s) of action.
AB  - Oromucosal cytokine therapy allows large amounts of cytokines to be administered
      with improved outcome and without dose limiting toxicity. Orally administered
      cytokines exert their effects by a novel two pronged mechanism of action.
      Firstly, specific populations of immuno-competent effector cells are activated in
      the oral cavity and migrate to the site of virus replication. Secondly,
      chemokines produced in the lymphoid tissue of the oral cavity enter the
      peripheral circulation and redirect activated lymphocytes to eliminate virus
      infected cells. Oromucosal IFN therapy constitutes an alternative and improved
      means of therapy for diseases such as chronic viral hepatitis which are currently
      treated parenterally with IFN alpha. The oral route also has obvious advantages
      for ease of administration and improved patient compliance. Furthermore, the
      availability of a well tolerated form of IFN therapy will also allow Type I IFNs
      to be used for the treatment of diseases such as upper respiratory tract virus
      infections, for which parenteral IFN therapy is currently precluded due to
      unacceptable toxicity.

PMID- 12499798
TI  - [A study of polymorphism in UDP-glucuronosyltransferase 1 (UGT-1A1) promoter gene
      in Korean patients with Gilbert's syndrome].
AB  - BACKGROUND/AIMS: Hepatic glucuronidating activity, essential for efficient
      biliary excretion of bilirubin, is reduced to about 30 percent of normal in
      patients with Gilbert's syndrome. Patients with Gilbert's syndrome have an
      additional TA insertion in the A(TA)TAA of UDP-glucuronosyltransferase 1 (UGT
      1A1) promoter gene. This results in reduced frequency and accuracy of
      transcription initiation and enzyme activity. The frequency and location of the
      mutation vary according to races. This study was done to determine the UGT-1A1
      promoter gene mutation in Korean cases of Gilbert's syndrome. METHODS: Promoter
      regions of the gene for bilirubin UGT-1A1 in twelve patients with Gilbert's
      syndrome and twenty healthy subjects (controls) were sequenced. RESULTS: 1) Among
      twelve Gilbert's syndrome five patients were homozygous for A(TA)6/6TAA, two were
      homozygous for A(TA)7/7TAA, and the other five were heterozygous for A(TA)6/7TAA.
      The prevalence of A(TA)TAA mutation was 58.3 percent. 2) Among twenty healthy
      subjects seventeen were homozygous for A(TA)6/6TAA, one was homozygous for
      A(TA)7/7TAA, and two were heterozygous for A(TA)6/7TAA. The prevalence of
      A(TA)TAA mutation was 15 percent. 3) The prevalence of A(TA)TAA mutation in
      Gilbert's syndrome patients was significantly higher than in the controls
      (p=0.018). CONCLUSION: Although the prevalence of A(TA)TAA mutation in Korean
      patients with Gilbert's syndrome is significantly higher than in the controls,
      the mutations of the promoter region of UGT-1A1 gene appear not to be the main or
      sole cause in Gilbert's syndrome in Korea since the prevalence of A(TA)TAA
      mutation is not so high. Further studies to determine the relationship between
      other UGT-1A1 gene mutation and Gilbert's syndrome in Korea are needed.

PMID- 12499799
TI  - [Direct analysis of HBV-specific CD8+ lymphocyte by tetrameric HLA-A2/core 18-27
      complex in chronic Hepatitis B].
AB  - BACKGROUND/AIMS: Hepatitis B virus(HBV) specific cytotoxic T lymphocyte (CTL)
      response is believed to play a major role in virus control and liver damage in
      chronic hepatitis B(CHB). We performed this study to evaluate whether HBV
      specific CTL could be visualized directly by tetrameric HLA-A2/core 18-27
      complex(T c18-27) in the peripheral blood and liver of patients with CHB. On the
      basis of our results we clarified patients intrahepatic compartmentalization and
      correlation with HBV specific CTL and viral replication or liver damage. METHODS:
      We stained peripheral blood mononuclear cells of 33 HLA-A2 + and 8 HLA-A2
      patients with CHB with cytochrome conjugated anti-CD8 mAb and phycoerythrin
      conjugated T c18-27. Among these we analysed intrahepatic lymphocyte of 11 HLA-A2
      + patients. We compared the frequency of T c18-27 specific CD8+ cells with serum
      HBV-DNA levels or alanine aminotransferase(ALT) levels. RESULTS: The frequency of
      circulating T c18-27 specific CD8+ cell was higher(9-101 cells per 50,000 CD8+
      cells) than background level in 14 among 33 patients. The frequency of
      intrahepatic T c18-27 specific CD8+ cells was 12-2100 cells per 50,000 CD8+ cells
      in 8 out of 11 patients whose liver was obtained This was 17.4-150 times higher
      than circulating T c18-27 specific CD8+ cells. The frequency of circulating T c18
      27 specific CD8+ cells was increased in 10 out of 18 patients with serum HBV DNA
      level <0.5 pg/mL and ALT < 40 IU/L. It was increased in just 4 out of 15 patients
      with HBV DNA level > 800 pg/mL and ALT > 70 IU/L. The frequency of intrahepatic T
      c18-27 CTL tended to be lower in high levels of serum HBV DNA and was not
      correlated with liver inflammation. CONCLUSION: This study proves that if HBV
      specific CTLs are barely detectable in the peripheral blood of CHB, much more HBV
      specific CTLs are in the liver and most HBV-specific CTLs are infiltrated in the
      liver. Also, in the presence of an effective HBV specific CD8 response the
      inhibition of viral replication can be independent of liver damage.

PMID- 12499800
TI  - [The prevalence and clinical significance of precore and core promoter mutations
      in Korean patients with chronic hepatitis B virus infection].
AB  - BACKGROUND/AIMS: Precore and core promoter mutations of hepatitis B virus (HBV)
      have been reported in Korea but their prevalence and clinical significance have
      not been determined. The aims of this study were to determine the prevalence of
      precore and core promoter mutations and their relationships to hepatitis B e
      antigen (HBeAg) status, viral replication level, and severity of liver disease in
      Korea. METHODS: Among the patients who visited the Liver Diseases Clinics (Chung
      Ang University Hospital) between December 1998 and August 1999, 150 patients were
      randomly selected: 50 HBeAg-positive HBV-DNA positive patients by a branched DNA
      (bDNA) assay, 50 HBeAg-negative bDNA-positive patients, and 50 HBeAg-negative
      bDNA-negative patients. Serum HBV-DNA was amplified by a polymerase chain
      reaction (PCR) in these patients and the core promoter/precore HBV sequence was
      determined in 135 of the patients whose sera were positive for HBV-DNA by PCR.
      RESULTS: All of the 135 determined HBV-DNA sequences had HBV genotype with T at
      nucleotide 1858. Precore mutation (A1896) was detected in 95.7% of HBeAg-negative
      bDNA-positive patients and 94.9% of HBeAg-negative bDNA-negative patients. In
      HBeAg-positive patients 88% had wild type and 12% had mixture of wild type and
      A1896 mutant. Core promoter TA mutation (T1762/A1764) was detected in 93.5% of
      HBeAg-negative bDNA-positive patients, 94.9% of HBeAg-negative bDNA-negative
      patients and 74% of HBeAg-positive patients. No correlation was found between the
      presence of precore/core promoter mutations and liver disease severity or HBV-DNA
      levels. CONCLUSION: Precore stop codon mutation occurred almost invariably, along
      with HBeAg seroconversion, irrespective of subsequent viral replication levels or
      disease severity. Core promoter TA mutation was frequent both in the HBeAg
      positive patients and HBeAg-negative patients irrespective of viral replication
      levels or disease severity.

PMID- 12499801
TI  - [The clinical significance of quantitation of HBV DNA in serum-comparison of the
      branched-DNA assay with the second-generation digene hybrid capture assay and
      long-term observation].
AB  - BACKGROUND/AIMS: Serum levels of hepatitis B virus (HBV) DNA are direct measures
      of viral replication in hepatocytes. We compared branched-DNA assay
      (Quantiplex(TM), bDNA) and Hybridization Capture II (HCII), and evaluated the
      clinical significance of HBV DNA quantitation in the natural course of HBV
      infection. METHODS: We analyzed results of bDNA in 324 serum samples from 83
      untreated male patients with chronic hepatitis B. Mean follow up period was 11.8
      years. HCII was also performed in 157 arbitrarily selected samples. RESULTS: HBV
      DNA levels measured with two assays were very similar (r(2)=0.893, p<0.0001). HBV
      DNA detection rate of HCII was 6.4% higher than that of bDNA in HBeAg positive
      samples. HBV DNA detection rate was higher in cases with higher ALT. Among 73
      patients with initial diagnosis of chronic hepatitis, 38 patients (52.1%)
      experienced progression to cirrhosis, and hepatocellular carcinoma (HCC) was
      developed in 9 (12.3%). HCC was developed in 5 (50.0%) of 10 patients with
      initial diagnosis of cirrhosis. While HBeAg positive rates during chronic
      hepatitis, cirrhosis and HCC were 57.8%, 55.0% and 14.3%, respectively (p=0.006),
      HBV DNA detection rates were 70.6%, 64.0% and 42.9%, respectively (p=0.08).
      Especially in HCC, the discrepancy between HBeAg positive rate and HBV DNA
      detection rate may suggest the appearance of variants which cannot produce HBeAg.
      CONCLUSION: Both HCII and bDNA were similar HBV DNA quantitation assays for
      clinical use. HBV DNA level correlated with the severity of liver disease.
      Screening tests for HCC should be recommended in patients whose HBeAg is negative
      and have detectable HBV DNA.

PMID- 12499802
TI  - [Electron microscopic mesenchymal response in chronic viral hepatitis].
AB  - BACKGROUND/AIMS: This study was designed to clarify the fine structures of the
      hepatocytes and mesenchymal tissues in chronic hepatitis according to severity.
      METHOD: For the purpose of elucidating the ultrastructural characteristics of
      mesenchymal tissues, liver biopsy specimens were studied by light and electron
      microscopy in 20 patients with chronic hepatitis. RESULTS: 1) Hepatocytes in
      mesenchymal tissues were thought to be in the stage of regenerated or degenerated
      process. 2) Regenerating nodules were surrounded by a basement membrane-like
      materials in the space of Disse. 3) In the widened Disse space the deposition of
      collagen fiber bundles and increased numbers of hepatic stellate cells in
      necrotic area were observed. 4) In necrotic areas, hepatic mesenchymal cell
      response including an increase of collagen fibers and fibroblast, angiogenesis,
      and a proliferation of bile ductules were also observed. CONCLUSIONS: These
      observations suggest that the fibrosis in severe chronic hepatitis was
      accompanied by the mesenchymal response including the proliferation of hepatic
      stellate cells, fibroblasts, capillarization of Disse space, and mesenchymal
      proliferation. Finally, this fibrosis observed electron microscopically may be a
      cause of functional hepatic failure.

PMID- 12499803
TI  - [An experimental model of hepatic fibrosis induced by alcohol and CCl4: can the
      lipopolysaccharide prevent liver injury induced by alcohol and CCl4?].
AB  - BACKGROUND/AIMS: It is well known that alcohol enhances the toxicity of CCl4. We
      tried to establish an alcoholic liver cirrhosis model by administration of
      alcohol and CCl4 to rats. We also wanted to know the hepatoprotective effect of
      low doses of lipopolysaccharide(LPS) in this animal model. METHODS: Of 20 female
      adult rats, 8 were ingested with alcohol ad libitum(group 1) Another 6 were
      ingested with 10% alcohol and 50% 1mL/kg CCl4 intragastrically by Sonde twice a
      week(group 2) The remaining 6 were ingested with 10% alcohol, CCl4, and 0.1mg/kg
      LPS intraperitoneally twice a week(group 3) The fibrosis was evaluated
      semiquantitatively on a scale of 0(none) to 3(cirrhosis). RESULTS: 1) After 10
      weeks, septal fibrosis or cirrhosis was produced in 9 out of 12 rats in groups 2
      and 3 but there was no fibrotic change in group 1. 2) There was no significant
      difference in pathological grading between groups 2 and 3. CONCLUSIONS: Hepatic
      fibrosis or cirrhosis can be sufficiently induced by alcohol and repetitive CCl4
      ingestion for 10 weeks. We can not prove the hepatoprotective effect of low dose
      LPS by semiquantitative evaluation of pathological grading.

PMID- 12499804
TI  - [The usefullness of percutaneous transluminal balloon angioplasty in the
      management of budd-Chiari syndrome].
AB  - BACKGROUND/AIMS: Membranous obstruction is the most common cause of Budd-Chiari
      syndrome in Orientals. Recently, percutaneous transluminal balloon angioplasty
      (PTBA) has been successfully applied as a treatment of membranous obstruction. We
      evaluated etiologies and clinical manifestations in our cases and the usefulness
      of PTBA. METHODS: Twelve cases of Budd-Chiari syndrome were analyzed. RESULTS:
      50.3 years was the average age of the cases (ranging from 37 to 67 years). Major
      symptoms or signs were superficial collateral vessels on the chest or the abdomen
      in 6 cases, ascites in 3, abdominal pain in 4, hepatomegaly in 4, splenomegaly in
      3, melena or hematemesis in 2, and leg edema in 2. Upper gastrointestinal
      endoscopy showed esophageal varices in 6 cases and two of these 6 cases had
      gastric varices. Of 8 cases with liver cirrhosis, 4 were classified as Child-Pugh
      class A and 4 as B. Four patients with cirrhosis had concurrent hepatocellular
      carcinoma including 1 patient who was HBs Ag positive. Etiologies were membranous
      obstruction in 11 cases and protein C deficiency in 1 case. The main site of
      obstruction was IVC in 8 and hepatic vein in 4. PTBA was successfully performed
      in 8 cases of membranous obstruction. During the mean follow-up period of 27.6
      months (12-40 months), there were no reobstructions except in 2 cases.
      CONCLUSIONS: The most common cause of Budd-Chiari syndrome in our cases was
      membranous obstruction of IVC. Percutaneous transluminal balloon angioplasty is a
      very useful treatment method.

PMID- 12499805
TI  - [A comparison of patients with hepatocellular carcinoma between a short-term
      (less than 6 months) survival group and a long-term (over 24 months) survival
      group after treatment with transcatheter arterial chemoembolization].
AB  - BACKGROUND/AIMS: Although hepatocellular carcinoma(HCC) shows poor prognosis,
      transcatheter hepatic arterial chemoembolization(TACE) can improve survival rate
      in some patient groups. This study investigated the synergy effect of the
      different clinical indices on the survival time in patients with HCC underwent
      TACE. MATERIALS AND METHODS: A retrospective study of 241 patients with HCC who
      underwent TACE with a mixture of lipiodol, mitomycin-C and adriamycin, alone or
      followed by gelfoam was conducted. Three different survival groups (A, less than
      6 months; B, between between 6 and 23 months; and C, over 24 months) were
      compared. RESULTS: Alkaline phosphatase was lowest in group C (p=0.0001). The
      longer the survival, the lower (p=0.027, p=0.007) the AST and AST/ALT ratio were.
      Albumin was higher (p=0.032), GGT and LDH were lower (p=0.003, p=0.002) in the
      long-term survival group. The long-term survival group revealed an absence of
      both ascites(p<0.002) and portal vein thrombosis(p<0.001), and lower TNM stage
      (P<0.0001). The single nodular type of HCC was more frequent (P<0.0001) and the
      size of tumor was smaller in the long-term survival group (P<0.0001). Child-Pugh
      class was lower in the long-term survival group (p=0.017). The higher serum
      albumin and elder age, the higher albumin and the lower alkaline phosphatase or
      alpha-fetoprotein, represented synergic effects on a long term survival. The
      higher albumin and the smaller size or the lower tumor stage, the higher albumin
      and platelet revealed similar synergy effects. Although the age or platelet is
      high, low albumin showed poor prognosis. CONCLUSION: Patients with small-sized
      single, nodular HCC in a low Child-Pugh class without evidence of ascites and
      portal vein thrombosis, and the higher level of serum albumin but lower levels of
      alpha-fetoprotein, alkaline phosphatase, GGT, and LDH, can expect a long-term
      survival over 24 months by the treatment of TACE. There are meaningful synergies
      of the different clinical variables affecting the survival times in the patients
      with HCC undergoing TACE.

PMID- 12499806
TI  - CT detection of hepatocellular carcinoma in advanced liver cirrhosis: correlation
      of helical CT and explanted liver.
AB  - OBJECTIVE: The objective of this study was evaluate the diagnostic efficacy of
      three-phase helical dynamic CT in the detection of hepatocellular carcinomas in
      patients with advanced liver cirrhosis. MATERIALS AND METHODS: Three-phase
      helical dynamic CT in 77 patients with advanced liver cirrhosis was evaluated
      prospectively before orthotopic liver transplantation. The histopathologically
      confirmed hepatocellular carcinomas in the explanted livers were compared with
      pretransplantation CT results by one-to-one correlation. RESULTS: Histopathologic
      examination of the explanted livers revealed 72 hepatocellular carcinomas in 41
      patients. The size of the hepatocellular carcinomas was 0.5-14.0 cm (mean, 1.6
      cm). The use of helical dynamic CT enabled the detection of 38 of 72
      hepatocellular carcinomas (sensitivity, 53%). Fifteen of 35 (43%) hepatocellular
      carcinomas smaller than 2 cm and 23 of 37 (62%), hepatocellular carcinomas
      ranging from 2.0 cm to 14.0 cm were detected. Patient sensitivity and specificity
      in the detection of hepatocellular carcinoma were 81% (33/41) and 94% (34/36),
      respectively. CONCLUSIONS: Three-phase helical dynamic CT is insensitive for
      detection of hepatocellular carcinomas in patients with advanced liver cirrhosis,
      especially for hepatocellular carcinomas smaller than 2 cm.

PMID- 12499807
TI  - [Laparoscopic and percutaneous ultrasound guided radiofrequency ablation for
      hepatocellular carcinoma: a preliminary study].
AB  - BACKGROUND/AIMS: Radiofrequency ablation (RFA) is emerging as a new therapeutic
      method in the management of hepatocellular carcinoma (HCC). We report the results
      of 64 patients with a follow-up interval of 3 to 19 months. METHOD: Sixty-four
      patients with 82 nodules underwent ultrasound guided RFA. The mean tumor diameter
      was 2.5+/-1.0 cm. Laparoscopic ultrasound guided RFA was performed in 38 cases,
      and percutaneous ultrasound guided RFA in 26 cases. The therapeutic efficacy was
      evaluated by means of three-phase dynamic abdominal computed tomography (CT)
      performed within at least one week after ablating. The recurrence was evaluated
      after treatment by means of abdominal CT and alpha fetoprotein every 3 months. We
      calculated cumulative recurrence rates, survival rates of patients, and found out
      complication of RFA. RESULTS: Cumulative recurrence rates in 3, 6, 12 months
      after RFA was 8.8%, 15.8%, 25.9%. 12 cases were recurred during follow-up. Among
      them, intrahepatic recurrences were noted in 11 cases, local recurrences in 3
      cases. Cumulative survival curves indicated that survival rate was 95% at the
      third month, 94% at the sixth month, 81% at the twelfth month. After RFA, the
      alpha fetoprotein level was decreased significantly after 1 month (p<0.05), and
      serum transaminase levels were transiently elevated (p<0.01) but returned to
      normal within one week. Complications of RFA were not serious, and resolved
      spontaneously. CONCLUSION: RFA can be considered a useful new treatment for HCC.
      Laparoscopic RFA is a useful procedure for the treatment of HCC regardless of its
      location.

PMID- 12499808
TI  - [A case of primary hepatocellular carcinoma with metastasis to the spinal cord].
AB  - Hepatocellular carcinoma is one of the most common malignancies reported in
      Korean adult males. Hepatocellular carcinoma usually spreads to regional lymph
      nodes around porta hepatis via lymphatics and to distant metastasis via
      hematogenous spread. The lung is most common distant metastatic site, followed by
      the adrenal glands, local lymph nodes and bones. But metastasis to the spinal
      cord of hepatocellular carcinoma is very rare. Recently we experienced a patient
      with hepatocellular carcinoma who had suffered from lower leg weakness for 10
      days. The patient was proved to have hepatocellular carcinoma with metastasis to
      the spinal cord. MRI showed an ovoid intracordal mass between the twelfth
      thoracic and first lumbar vertebra level. After emergency irradiation, the
      patient could recover.

PMID- 12499809
TI  - [Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two
      different dysplastic nodules].

PMID- 12499810
TI  - [Liver metastasis of colon cancer].

PMID- 12499811
TI  - [Ultrastructure of chronic liver diseases: endothelial cells of the hepatic
      sinusoids].

PMID- 12499812
TI  - Rhus-chicken.

PMID- 12499813
TI  - [Surgical management of hepatocellular carcinoma].

PMID- 12499814
TI  - [Liver cirrhosis and diabetes mellitus].

PMID- 12499815
TI  - [Validation of international autoimmune hepatitis group scoring system for
      diagnosis of type 1 autoimmune hepatitis in Korea].
AB  - BACKGROUND/AIMS: There are no pathognomonic features of autoimmune hepatitis
      (AIH). Its diagnosis requires the exclusion of various other conditions. The aim
      of this study was to validate indirectly the International Autoimmune Hepatitis
      Group (IAHG) scoring system in diagnosing AIH. METHODS: Twenty-six patients with
      Type 1 AIH and female patients with chronic hepatitis B (n=34), chronic hepatitis
      C (n=25), or toxic hepatitis (n=13) were evaluated according to 9 categories of
      pretreatment minimum required parameters proposed by IAHG. Aggregate scores of
      AIH to those of non-AIH groups, which were assessed before and after extracting
      the proportions of etiologic factors, were also compared and evaluated. RESULTS:
      While aggregate scores of non-AIH groups, before extracting the proportions of
      etiologic factors, were 5.2+/-1.8, 5.6+/-1.1, and 7.4+/-1.2 in that order, those
      of AIH groups were 12.8+/-1.7. These were significantly higher than those of non
      AIH groups (p<0.01). All patients in AIH groups and only 1 patient in a non-AIH
      group showed aggregate scores of more than 10. Aggregate scores after extracting
      the proportions of etiologic factors were more than 4 in all, except 2, patients.
      These should have been consistent with 10 if there were no etiologic factors in
      non-AIH groups. CONCLUSION: The IAHG scoring system might have a relatively
      excessive importance to the scores of categories excluding distinct etiologies
      from AIH. It might be difficult to differentiate AIH from chronic liver diseases
      of indistinct cause based on the IAHG scoring system.

PMID- 12499816
TI  - [HBV DNA levels, aminotransferase and histological activity in young male
      patients with HBeAg positive chronic hepatitis B].
AB  - BACKGROUND/AIMS: A significant correlation between HBV DNA and liver damage was
      found in precore mutant strains but there was no significant association between
      viral replication and liver damage in HBeAg positive patients. Laboratory tests
      are often requested to predict hepatitis activity (grade) and fibrosis (stage) in
      HBeAg positive chronic hepatitis B. We assessed ALT, AST, and HBV-branched DNA to
      find which is the best for predicting hepatitis activity and fibrosis. METHODS:
      Routine biochemical liver function tests and HBV DNA in sera were assessed in 119
      young patients positive with HBsAg and HBeAg. The mean age of patients was 21+/-2
      years. All patients were male. By logistic regression analysis the relationships
      between laboratory data, hepatitis activity, fibrosis, or risk of chronic active
      hepatitis were analyzed. RESULTS: There was a significant correlation between
      aminotransferase (AST, ALT) and hepatitis activity/ fibrosis. A significant
      inverse relationship between the HBV bDNA and hepatitis activity was demonstrated
      (Pearson's correlation coefficient: lobular activity,-0.305; porto-periportal
      activity, -0.410). But HBV bDNA was not correlated with severity of fibrosis. AST
      and HBV bDNA was the important test for predicting the more severe hepatitis
      activity (lobular activity and porto-periportal activity: score>/=3,
      respectively) CONCLUSION: The higher AST, but the lower HBV bDNA, in sera shows
      the more severe hepatitis activity. AST and HBV bDNA could be helpful for
      assessing the hepatitis activity in young male patients with HBeAg positive
      chronic hepatitis B if proper reference values are used.

PMID- 12499817
TI  - [Efficacy and safety of large volume paracentesis in cirrhotic patients with
      spontaneous bacterial peritonitis: a randomized prospective study].
AB  - BACKGROUND/AIMS: Large volume paracentesis (LVP) associated with plasma volume
      expansion is known to be an effective and safe therapy for tense or refractory
      ascites in cirrhosis. Spontaneous bacterial peritonitis (SBP) is one of the
      frequent infections in patients with cirrhosis. We conducted a study to assess
      the efficacy and safety of large volume paracentesis in cirrhotic patients with
      SBP. METHODS: We randomly assigned 40 patients with cirrhosis and SBP to either
      treatment with LVP (21 patients) or general management (19 patients). LVP was
      defined as drainage of ascitic fluid of more than 4 liters in a single tap or
      loss of shifting dullness after paracentesis. LVP was performed within 48 hours
      after the diagnosis of SBP in the LVP group. Cefotaxime was given daily in doses
      that varied according to the serum creatinine level in both groups. Albumin was
      given at a dose of 6-8 g per 1 liter of removed ascites in the LVP group.
      RESULTS: After seven days of treatments, the blood chemistry test, and WBC (PMN)
      counts and protein concentration in the ascitic fluid were not different between
      the two groups. Among them, the WBC (PMN) counts were decreased significantly in
      both groups and protein concentrations tended to increase. Durations of abdominal
      tenderness and pain were shorter in the LVP group but the differences were
      statistically not significant. Admission periods, resolution rates of SBP after
      seven days of treatment, complication rates and in-hospital mortality rates were
      not different between the two groups. CONCLUSIONS: The two treatment methods
      demonstrated almost the same effectiveness and safety. The symptoms were improved
      slightly faster in the LVP group. We concluded that large volume paracentesis is
      not an absolute contraindication and can be a tolerable and safe therapy in some
      selected cirrhotic patients with tense ascites and SBP.

PMID- 12499818
TI  - [Clinical and microbiological characteristics of spontaneous bacterial
      peritonitis (SBP) in a recent five year period].
AB  - BACKGROUND/AIMS: Recently, treatment failure with the third generation of
      cephalosporin was increasingly noted in patients with spontaneous bacterial
      peritonitis (SBP). We therefore were to evaluate the pattern of antibiotic
      resistance and its clinical significance. METHODS: We retrospectively analyzed
      580 episodes of SBP occurring between 1995 and 1999. There were 87 episodes of
      SBP in 1995, 222 in 1998, and 271 in 1999. The pattern of isolated organisms and
      antibiotic resistance, and prognostic factors for survival, were analyzed.
      RESULTS: Microorganisms were isolated in 41% of total episodes. The three most
      frequently isolated organisms were E. coli (48%), K. pneumoniae (15%), and
      Aeromonas (8%). The percentage of resistant strains to cefotaxime (9%, 14%, 32%)
      and ciprofloxacin (13%, 21%, 32%) significantly increased. The proportion of E.
      coli producing extended spectrum beta-lactamase (ESBL) also increased
      significantly (0%, 16%, 33%). The need of secondary antibiotics such as imipenem
      due to treatment failure was significantly increased from 0% in 1995 to 33% in
      1999. Overall in-hospital mortality, however, was not changed (20%, 20%, 24%,
      respectively). The factor affecting early mortality was renal failure at
      diagnosis. Prognostic factors for long-term survival were the presence of
      associated malignancy and ESBL-producing microorganisms. CONCLUSION:
      Microorgansims resistant to third generation cephalosporin and quinolone were
      increasingly isolated over the 5 years in patients with SBP. Measures to prevent
      in-hospital spread of resistant strains and indiscreet use of antibiotics should
      therefore be instituted.

PMID- 12499819
TI  - [Concurrent chemo-radiation therapy for advanced hepatocellular carcinoma with
      portal vein thrombosis].
AB  - BACKGROUND/AIMS: Advanced hepatocellular carcinoma with portal vein thrombosis
      has a poor prognosis. This study was undertaken to evaluate the therapeutic
      effects of concurrent chemo-radiation therapy in advanced hepatocellular
      carcinoma with portal vein thrombosis. METHODS: A total of 54 patients with
      advanced hepatocellular carcinoma (TNM stage IVa) were enrolled. Nineteen
      patients were treated with external beam radiotherapy (4,500 cGy/ 5 weeks) and
      intrahepatic arterial 5-FU infusion (500 mg on 1-5 day and 30-35 day,
      respectively) via implanted chemoport. The others were treated with intrahepatic
      arterial cisplatin infusion (80 mg/m(2)). RESULTS: In patients treated with
      concurrent chemo-radiation therapy, response rates at 2nd and 6th months were
      42.1% and 26.3%, respectively. In patients treated with intrahepatic arterial
      cisplatin therapy, response rates at 2nd and 6th months were 2.9% and 0%,
      respectively. The median survival time was 11.6 months in concurrent chemo
      radiation therapy and 4.8 months in intrahepatic arterial cisplatin infusion
      therapy. Concurrent chemo-radiation therapy produced better response rates and
      longer survival time than those of intrahepatic arterial cisplatin infusion
      therapy (p<0.05). CONCLUSIONS: Concurrent chemo-radiation therapy achieved
      favorable results in advanced hepatocellular carcinoma with portal vein
      thrombosis and can be considered as a treatment option for the management of
      advanced hepatocellular carcinoma.

PMID- 12499820
TI  - [Interactions of unconjugated bilirubin with bile acid by rapid solvent
      partition].
AB  - BACKGROUND/AIMS: Our previous studies of ionization and solubility of
      unconjugated bilirubin (UCB) yielded inappropriately large differences between
      the two carboxylic pK'a values of UCB. These data, however, were not ideal due to
      crystal effects, matastability, impurities of the bilirubin, and imprecision of
      analyses at low UCB. METHODS: The sodium salt of taurocholate (TC) was purified
      and dissolved in water to 100 mM. Chloroform (CHCl3) was purified by vacuum
      distillation. Buffers used were: citrate from pH 4 to 6, phosphate from pH 6 to
      8, and borate above pH 8. All had an ionic strength of 0.10. The problems were
      minimized by rapid solvent partition of UCB from CHCl3 into buffered aqueous
      NaCl, and a new, accurate assay of low UCB in the aqueous phase which was
      achieved by concentrating the UCB through back extraction into small volumes of
      CHCl3. RESULTS: In contrast with the crystal dissolution studies, the two pK'a
      value were similar. H2B0, not HB-, was the dominant UCB species in the pH range
      of bile (6.0 to 8.0). The aqueous solubilities of UCB were 90 to 98% less. Less
      than 0.01% of the bile salt partitioned into the CHCl3 phase and self-association
      of B= was negligible. UCB solubilities in 50 mM TC were 2 to 10% of those
      obtained by crystal dissolution, and, up to pH 7.9, were below the maximum UCB
      concentration in normal human bile. CONCLUSIONS: We suggest that the markedly
      increased binding of UCB with each ionization step is due to the disruption of
      the internal hydrogen bonds of the ionized carboxyl groups on interaction with
      the bile salt. We propose to extend the study of partition to determine the
      activity and the degradation products of calcium salts of unbound bilirubin
      fractions.

PMID- 12499821
TI  - [The expression of E-cadherin in human and rat hepatic stellate cells: evidence
      of epithelial-mesenchymal transition].
AB  - BACKGROUND/AIMS: The embryonal origin of hepatic stellate cells (HSCs), the
      principal cells in hepatic fibrogenesis, is still intriguing. We have previously
      demonstrated that human HSCs express cytokeratins which suggests the epithelial
      origin of these cells. To further explore the origin and the differentiation of
      HSCs we studied the expression of E-cadherin, the specific marker of epithelial
      cells, in human and rat HSCs. METHODS: We studied the changing pattern of E
      cadherin expression during spontaneous activation of primarily isolated human
      HSCs by immunofluorescence staining and RT-PCR. To confirm the expression of E
      cadherin in HSCs in vivo we performed double immunofluorescence staining for E
      cadherin and glial fibrillary acidic protein, the specific identification marker
      of quiescent rat HSCs, in normal rat liver. RESULTS: Quiescent human HSCs were
      labeled strongly by anti-E-cadherin monoclonal antibody at the first and seventh
      days after primary culture. Human HSCs, however, did not stain for E-cadherin
      after the first passage of culture. RT-PCR also confirmed these modulations of E
      cadherin expression. Double immunofluorescence staining, performed on rat liver
      tissue and observed by confocal laser scanning microscopy, unequivocally revealed
      the membranous expression of E-cadherin in quiescent HSCs labeled by glial
      fibrillary acidic protein. CONCLUSIONS: Quiescent HSCs of humans and rats express
      E-cadherin both in vitro and in vivo. The extent of E-cadherin expression rapidly
      decreases during the process of spontaneous activation. Our results suggest that
      HSCs may be of epithelial origin and undergo epithelial-mesenchymal transition
      during activation process.

PMID- 12499822
TI  - [A case of fulminant hepatic failure in Wilson's disease combined with systemic
      lupus erythematosus].
AB  - Patients with systemic lupus erythematosus (SLE) have a chance of developing
      liver involvement in their lifetime. The main cause of liver involvement in SLE
      patients is previous treatment with hepatotoxic drugs or hepatotropic viral
      hepatitis. Wilson's disease is a hereditary disorder and is usually diagnosed in
      patients presenting either neuropsychiatric disorders or manifestations related
      to chronic liver disease. Fulminant hepatic failure as the initial manifestation
      of Wilson's disease is rare. The relationship between systemic lupus
      erythematosus and Wilson's disease has not been established. We report a case of
      a 12-year-old girl with SLE who presented fulminant hepatic failure as an initial
      manifestation of Wilson's disease. The diagnosis was established with decreased
      serum ceruloplasmin level and the presence of Kayser-Fleischer ring. We treated
      with repeated plasma exchange. Despite repeated plasma exchange she died of multi
      organ failure on the 16th hospital day. Considering this case, Wilson's disease
      should be considered as a cause of fulminant hepatic failure, especially in
      juvenile age cases.

PMID- 12499823
TI  - [Internet for patient education of liver diseases].

PMID- 12499824
TI  - [Hepatocellular carcinoma arising in hepatocellular adenoma].

PMID- 12499825
TI  - [Peripheral cholangiocarcinoma].

PMID- 12499826
TI  - [Ultrastructure of chronic liver diseases: From light to electron microscopy].

PMID- 12499827
TI  - [Dural bone defects and encephalocele associated with chronic otitis media or its
      surgery].
AB  - OBJECTIVES: We investigated the incidence of dural bone defects and encephalocele
      following radical mastoidectomy or open cavity tympanoplasty. PATIENTS AND
      METHODS: We retrospectively evaluated 190 operations of 182 patients (97 males,
      85 females; mean age 30.6 years; range 9 to 70 years) who underwent radical
      mastoidectomy (n=89) or open cavity tympanoplasty (n=101). Follow-up examinations
      included otomicroscopy. Patients with documented dural bone defects on
      examination or operation records were further evaluated by axial and coronal
      computed tomography scans of the temporal bone. Those with suspected
      encephalocele were studied by magnetic resonance imaging. RESULTS: Dural bone
      defects were detected in 17 patients perioperatively. Of these, 14 defects were
      associated with chronic otitis media. Three iatrogenic bone defects were induced
      during obliteration of lateral sinus thrombosis. The mastoid tegmen was the most
      common site of defects (41%) and the most common etiologic factor was
      cholesteatoma (84%). Encephalocele was detected in one patient in whom radical
      mastoidectomy with lateral sinus obliteration was performed due to lateral sinus
      thrombophlebitis. Encephalomalasia was found nearby the defect area in two
      patients. CONCLUSION: Dural bone defects associated with chronic otitis media are
      not rare, the most common cause being cholesteatoma. Repair of dural lacerations
      requires watertight closure to prevent the occurrence of encephalocele.

PMID- 12499828
TI  - [The relationship between the presence of Candida colonization in the oropharynx
      and on the Blom-Singer voice prosthesis and its effect on the length of
      prosthesis use].
AB  - OBJECTIVES: We investigated the effect of oropharyngeal Candida colonization on
      the contamination of the Blom-Singer voice prosthesis and its lifetime. PATIENTS
      AND METHODS: The study included 26 male laryngectomized patients (age range 45 to
      76 years) in whom the Blom-Singer low-pressure prosthetic valve inserted required
      removal due to improper functioning. All patients had postoperative radiotherapy.
      Patients who had nystatin therapy were excluded. At the time of removal, cultures
      were obtained from the esophageal end of the prosthesis and from the oropharynx
      to be examined with regard to Candida growth. RESULTS: Candida colonization was
      recovered from the cultures obtained on 20 prostheses (77%) and from 14
      oropharyngeal specimens (54%). The presence of oropharyngeal colonization was
      always associated with that on prostheses. The average lengths of prosthesis use
      were 5.7 months (range 4 to 9 months) and 6.2 months (range 3 to 10 months) in
      patients with and without positive oropharyngeal Candida colonization,
      respectively (p>0.05). CONCLUSION: The results suggest that the presence of
      oropharyngeal Candida colonization has no effect on the prosthesis lifetime.

PMID- 12499829
TI  - [The prognostic significance of DNA ploidy in laryngeal cancers].
AB  - OBJECTIVES: We assessed the relationship between DNA ploidy and histopathologic
      parameters and its effect on prognosis in patients with squamous cell carcinoma
      of the larynx. PATIENTS AND METHODS: Surgical sections of 44 patients who were
      treated for squamous cell carcinoma of the larynx were studied. Image cytometry
      measurements were performed on nuclear suspensions derived from paraffin-embedded
      sections to determine DNA ploidy patterns. We investigated the relationship
      between the DNA ploidy status and localization, stage, differentiation,
      keratinization, depth of tumoral invasion, lymphocytic infiltration, perineural
      invasion, infiltration pattern, necrosis, and 5-year and overall survival rates.
      RESULTS: Aneuploidy and diploidy were diagnosed in 65.9% and 34.1%, respectively.
      No significant relationships were found between DNA ploidy and stage,
      localization, differentiation, keratinization, depth of invasion, infiltration
      pattern, lymphocytic infiltration, necrosis, perineural invasion, and lymph node
      metastasis (p>0.05). The five-year (p=0.048) and overall (log rank=4.40; p=0.036)
      survival rates were significantly higher in diploid tumors. The presence of
      perineural invasion (p=0.004) and depth of the invasion exceeding 9 millimeters
      (p=0.045) were significant factors adversely influencing the five-year survival
      rate. The multivariate Cox regression analysis showed that the DNA ploidy status
      (p=0.042) and the presence of perineural invasion (p=0.009) were independent
      prognostic variables related to decreased survival. CONCLUSION: Aneuploidy has an
      adverse effect on the prognosis in squamous cell carcinoma of the larynx.

PMID- 12499830
TI  - [A case of sinonasal lymphoma].
AB  - Sinonasal lymphoma is a rare disease that poses difficulties in diagnosis. A
      fifty-year-old male patient presented with a mass in the nasal vestibulum that
      destroyed the left nasal ala. Nocardiosis was considered in the light of the
      initial biopsy findings; however, microbiologic studies were not consistent with
      pathologic examination. A subsequent biopsy was obtained, which resulted in the
      diagnosis of peripheral T-cell lymphoma. Following the diagnosis, the patient was
      referred to the oncology clinic to receive chemotherapy. He died during the
      second course of chemotherapy.

PMID- 12499831
TI  - [The need for successive free flap applications for soft-tissue reconstruction in
      a case with recurrent oral carcinoma].
AB  - A case of difficult oncologic oral reconstruction is illustrated, in which soft
      tissue deficits resulting from failure of conventional techniques were treated by
      successive free tissue transfers. A thirty-eight-year-old man presented with
      squamous cell carcinoma in the right retrotrigonal region. The tumor was resected
      and the defect was reconstructed with the use of a tongue flap and skin graft.
      However, trismus occurred following radiotherapy, which was released by the help
      of a radial forearm free flap. The patient developed local recurrence several
      months later and right hemimandibulectomy, total maxillectomy, and
      hemiglossectomy were performed. The resulting en bloc defect was reconstructed by
      a free fibula osteocutaneous flap combined with a pedicled extended pectoralis
      major myocutaneous flap. The pectoralis flap was complicated by partial necrosis
      resulting in a large orocutaneous fistula and oral commissure incompetence. As
      the source of either a local or regional flap was inadequate, an anterolateral
      thigh myocutaneous free flap was used to fill the maxillary defect. No
      complications were encountered associated with free tissue transfers and the
      patient was able to take a soft diet three weeks after the final procedure.

PMID- 12499832
TI  - [Graft materials used in the reconstruction of saddle nose].
AB  - A large number of graft materials, either biologic or alloplastic, has been
      described in the reconstruction of saddle nose deformity to provide a structural
      support to the nasal dorsum and tip. Although autogenous materials are thought to
      be more advantageous, there is still no consensus regarding the most suitable
      surgical graft material for saddle nose. Each graft material presents some
      advantages and disadvantages. This article reviews current knowledge about graft
      materials used in the treatment of saddle nose deformity.

PMID- 12499833
TI  - Galvanic vestibular stimulation evokes sensations of body rotation.
AB  - Psychophysical experiments identified effects of galvanic vestibular stimulation
      (GVS) on the perception of whole-body angular rotation. Subjects lay supine on a
      platform that could rotate about a vertical axis through the vestibular axis so
      that linear movements were excluded. Movements were applied sufficiently above
      perception threshold to enable a reliable report of direction and movement size.
      In some trials, binaural GVS was applied concurrently at 1-2 mA. When GVS that
      was incongruent with the movement was applied, subjects reported lesser spin, on
      average cancelling the movement perception. When the GVS and movement were
      congruent, subjects reported greater spin. We conclude that GVS produces a
      vestibular signal of rotation, probably though an effect on semicircular canals.

PMID- 12499834
TI  - Neuronal injury affects expression of helix-loop-helix transcription factors.
AB  - Helix-loop-helix transcription (HLH) factors regulate several stages of neuronal
      development including differentiation of individual populations of neurons and
      neurite growth. Here we demonstrate that axonal injury of corticospinal and
      dorsal root ganglion neurons induces changes in the expression of several HLH
      transcription factors that function as negative regulators of neurogenesis and
      neurite outgrowth. However, the expression of HLH transcription factors that
      stimulate neurogenesis is not affected by the axonal injury. Expression of HES,
      SHARP and Id family members is suppressed shortly after axonal injury and
      expression returns to normal levels after 14 days. We hypothesize that down
      regulation of these HLH transcription factors is required for initiation of
      regenerative response to axonal injury.

PMID- 12499835
TI  - Functional identification of a cloned squid presynaptic voltage-dependent calcium
      channel.
AB  - We previously cloned a voltage-dependent Ca2+ channel alpha1 subunit LoCa(v)2
      cDNA from the squid optic lobe. LoCa(v)2 is designated as a non-L-type voltage
      dependent Ca2+ channel based on its amino acid sequence. We performed functional
      expression experiments of LoCa(v)2 in oocytes and characterized the expressed
      currents electrophysiologically and pharmacologically. The LoCa(v)2 current was
      high voltage-activated and the peak current was maximal at +20 mV and lasted for
      long during activation. The LoCa(v)2 current was not inhibited by the drugs and
      toxins examined except for omega-agatoxin IVA and PLTX-II. Omega-agatoxin IVA,
      which is a P-type channel blocker, moderately inhibited the LoCa(v)2 current at
      higher concentration. PLTX-II, which blocks insect presynaptic Ca2+ channel,
      inhibited the LoCa(v)2 current at lower concentration. Immunohistochemical
      investigation showed that the LoCa(v)2 protein may exist at presynaptic terminals
      in the squid optic lobe. These results suggest that LoCa(v)2 is an omega-agatoxin
      IVA and PLTX-II-sensitive presynaptic Ca2+ channel in the squid nervous system.

PMID- 12499836
TI  - Functional asymmetry in sheep temporal cortex.
AB  - Sheep, like humans, show a bias in favour of the left visual field when
      discriminating familiar faces. This, in humans, is thought to be caused by a
      right hemisphere dominance for processing faces involving the temporal cortex. We
      have directly investigated inter-hemispheric differences in face-processing in
      sheep by recording the frequencies and response profiles of single cells in the
      temporal cortex which respond selectively to faces. While there was no evidence
      for increased frequencies of face-sensitive neurones within the right temporal
      cortex, or their relative selectivity for individual faces, there was a
      pronounced response latency difference between the two hemispheres. The cells in
      the left hemisphere responding selectively to particular faces did so up to 400
      ms later than those in the right and with a greater degree of temporal
      variability between cells. No hemispheric latency differences were found,
      however, in other cells responding to general visual stimuli or to many faces.
      The data suggest that, while specialised face-sensitive neural circuits in the
      right hemisphere may play a key role in the rapid (< 200 ms) identification and
      discrimination of facial identity, those on the left may be involved more with
      slower processes associated with integrating the emotional or mnemonic
      consequences of recognition.

PMID- 12499837
TI  - Transcranial magnetic stimulation induces increases in extracellular levels of
      dopamine and glutamate in the nucleus accumbens.
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive approach used for
      stimulating the human brain. Repetitive stimulation over the prefrontal cortex
      has proven effective in the treatment of major depression, however the mechanism
      of the antidepressant action is unknown. Since the nucleus accumbens is a major
      region implicated in reward circuitry and depressive disorders, we used the
      microdialysis technique to study some of the neurochemical changes induced in
      that region during and after acute TMS. Magnetic stimulation was applied over the
      frontal or the caudal cortex of the rat brain using a special coil design and
      microdialysis samples were collected before, during and after the stimulation
      session. The extracellular levels of both dopamine and glutamate in the nucleus
      accumbens were increased during the stimulation while the extracellular levels of
      acetylcholine were not affected. Stimulation over the caudal cortex caused a
      greater increase in dopamine levels than the stimulation over the frontal cortex,
      while such difference was not observed for glutamate levels. The changes in
      dopamine and glutamate extracellular levels in the nucleus accumbens may play a
      role in the antidepressant effect of TMS and it is therefore suggested that the
      effect of stimulation over caudal cortical sites on depressive patients will be
      examined.

PMID- 12499838
TI  - Neural factors underlying reduced postural adaptability in children with cerebral
      palsy.
AB  - This study aimed to test mechanisms underlying impairments in balance control in
      children with cerebral palsy. We hypothesized that balance loss during large/fast
      perturbations could be due to reduced contraction of agonist muscles, delay in
      muscle contraction or simultaneous contraction of antagonist muscles, reducing
      the efficiency of the agonist burst. Electromyograms were recorded as children
      recovered from balance threats of varying magnitudes/velocities. In typically
      developing children muscle response magnitudes increased with larger/faster
      perturbations, while in children with cerebral palsy they did not. There was no
      difference in muscle onset latency or antagonist co-contraction between groups.
      Thus the primary constraint on balance recovery in these children is insufficient
      levels of contraction of agonist postural muscles.

PMID- 12499839
TI  - Neurite branching on deformable substrates.
AB  - The mechanical properties of substrates underlying cells can have profound
      effects on cell structure and function. To examine the effect of substrate
      deformability on neuronal cell growth, protein-laminated polyacrylamide gels were
      prepared with differing amounts of bisacrylamide to generate substrates of
      varying deformability with elastic moduli ranging from 500 to 5500 dyne/cm. Mouse
      spinal cord primary neuronal cells were plated on the gels and allowed to grow
      and extend neurites for several weeks in culture. While neurons grew well on the
      gels, glia, which are normally co-cultured with the neurons, did not survive on
      these deformable substrates even though the chemical environment was permissive
      for their growth. Substrate flexibility also had a significant effect on neurite
      branching. Neurons grown on softer substrates formed more than three times as
      many branches as those grown on stiffer gels. These results show that mechanical
      properties of the substrate specifically direct the formation of neurite
      branches, which are critical for appropriate synaptic connections during
      development and regeneration.

PMID- 12499840
TI  - Neurons and plaques of Alzheimer's disease patients highly express the neuronal
      membrane docking protein p42IP4/centaurin alpha.
AB  - The protein p42(IP4) (also called centaurin alpha), identified as a brain
      specific InsP4/PtdInsP3 (PIP3)-binding protein, has been shown to be localized in
      human brain, specifically expressed in neurons. Several casein kinases have been
      found to be involved in Alzheimer's disease (AD) pathology. Since casein kinase I
      was reported to possess a binding domain for p42(IP4), we here investigated the
      expression and localization of p42(IP4) in AD brains. In cortical neurons of AD
      brains intracellular immunostaining for p42(IP4) exceeded the level seen in these
      neurons of normal brain. Statistically, significantly more p42(IP4)
      immunoreactive neurons were found in temporal and angular cortex of AD patients
      as compared to control brain. Mostly impressively, neuritic plaques displayed a
      very prominent signal. Thus, we suggest that the up-regulated p42(IP4) in AD
      neurons may serve as a docking protein to recruit signaling molecules such as
      different subtypes of casein kinase I to the plasma membrane. This is the first
      indication for a functional interaction of these protein in possible neuronal
      damage. Therefore proteins such as p42(IP4), central players in signaling, may be
      appropriate targets for preventing neurodegenerative processes.

PMID- 12499841
TI  - Retinal precursor cells express functional ionotropic glutamate and GABA
      receptors.
AB  - R28 retinal progenitor cells offer the potential to replace damaged neurons;
      however, their ability to differentiate into the appropriate phenotype may depend
      on whether they express glutamatergic and GABAergic receptors. Whole-cell
      recordings and immunocytochemistry were used to identify glutamatergic and
      GABAergic receptors on proliferating R28 cells. R28 cells lacked voltage-gated
      channels; however, they produced inward currents when non-NMDA, NMDA, GABAa and
      GABAb receptor agonists were perfused onto the cells. R28 cells were
      immunoreactive to GluR1, 2 and 3, NMDA and GABAa receptors consistent with
      electrophysiological results. These results indicate that R28 progenitor cells
      express glutamatergic and GABAergic receptors capable of influencing their fate
      and function when grafted into retina or elsewhere in the nervous system.

PMID- 12499842
TI  - Variable effects of aging on frontal lobe contributions to memory.
AB  - Declarative memory declines with age, but there is profound variation in the
      severity of this decline. Healthy elderly adults with high or low memory scores
      and young adults viewed words under semantic or non-semantic encoding conditions
      while undergoing fMRI. Young adults had superior memory for the words, and
      elderly adults with high memory scores had better memory for the words than those
      with low memory scores. The elderly with high scores had left lateral and medial
      prefrontal activations for semantic encoding equal to the young, and greater
      right prefrontal activation than the young. The elderly with low scores had
      reduced activations in all three regions relative to the elderly with high memory
      scores. Thus, successful aging was characterized by preserved left prefrontal and
      enhanced right prefrontal activation that may have provided compensatory encoding
      resources.

PMID- 12499843
TI  - Phosphorylation of eukaryotic initiation factor-2alpha (eIF2alpha) is associated
      with neuronal degeneration in Alzheimer's disease.
AB  - Inhibition of protein translation is a mode of inducing neuronal apoptosis and
      neurodegeneration in Alzheimer's disease (AD). Phosphorylation of eukaryotic
      initiation factor-2alpha (eIF2alpha) terminates global protein translation and
      induces apoptosis. We examined whether this signaling pathway occurs in
      degenerating neurons of AD. Brain sections from young individuals, age-matched
      control individuals and AD patients were examined for immunoreactivity of
      phosphorylated eIF2alpha by immunohistochemical analysis. While young brain
      sections did not display and age-matched brain sections have mild immunoreactive
      positive cells, AD brain sections revealed intense immunoreactivity for
      phosphorylated eIF2alpha. Most of the phosphorylated eIF2alpha immunoreactive
      positive neurons have high immunoreactivity for phosphorylated tau using AT8
      antibody. Also, intense staining of phosphorylated eIF2alpha is associated
      vacuoles in degenerating neurons. This phenomenon was also observed for the
      immunohistochemical staining of phosphorylated PKR (double-stranded RNA-dependent
      protein kinase), the upstream kinase for eIF2alpha. Activation of PKR-eIF2alpha
      pathway is considered to be pro-apoptotic. In addition, formation of autophagy is
      regulated by eIF2alpha kinase. Therefore, it is concluded that phosphorylation of
      eIF2alpha is associated with the degeneration of neurons in AD.

PMID- 12499844
TI  - Layer-specific expression of Cl- transporters and differential [Cl-]i in newborn
      rat cortex.
AB  - GABA is the main inhibitory neurotransmitter in the adult brain. However,
      GABAergic transmission is depolarizing during early postnatal development,
      suggesting that changes in the expression of cation-Cl- co-transporters
      regulating neuronal Cl- homeostasis underlie the ontogeny of GABAergic functions.
      The developmental changes in the expressions of Cl- co-transporter mRNAs in the
      neocortex were in opposite directions for NKCC1 (Cl- uptake) and KCC2 (Cl-
      extrusion). In the newborn, NKCC1 mRNA expression was highest in ventricular zone
      followed by cortical plate, and then by Layer V/VI, while the reverse was true
      for KCC2 mRNA. The [Cl-]i levels were in the same rank order as for NKCC1 mRNA.
      Thus, the ontogeny of Cl- homeostasis in neocortical neurons could be regulated
      via the differential expression of NKCC1 and KCC2.

PMID- 12499845
TI  - Bcl-2 up-regulates ha-ras mRNA expression and induces c-Jun phosphorylation at
      Ser73 via an ERK-dependent pathway in PC 12 cells.
AB  - Members of the Bcl-2 family of proteins function either to promote or to repress
      apoptosis. Bcl-2 has been mainly localised to the mitochondria and acts
      predominantly upstream of cytochrome c release in its prevention of apoptosis.
      Little is known about the function of Bcl-2 independent of an apoptotic stimulus.
      Here we demonstrate that inducible overexpression of the anti-apoptotic protein
      Bcl-2 in a PC12 Tet-on- cell line up-regulates mRNA expression and leads to
      phosphorylation of c-Jun at Ser73 via the ERK pathway in a time and concentration
      dependent manner. Phosphorylation of c-Jun was inhibited by the addition of the
      selective ERK inhibitor PD 98059. No activation of the stress-activated protein
      kinases JNK and p38 could be detected. This is the first evidence of a direct
      activation of the Ras-Raf-MAPK cascade by an anti-apoptotic protein. We propose
      that the selective activation of Ras, the ERK pathway and the subsequent
      phosphorylation of c-Jun contribute to the anti-apoptotic action of Bcl-2.

PMID- 12499846
TI  - RAC1-dependent regulation of cholinergically induced lamellar protrusive activity
      is independent of MAPKinase and attenuated by active p-JNK.
AB  - In SH-SY5Y neuroblastoma cell bodies and growth cones the actin dynamics of
      cholinergically induced lamellar protrusion is demonstrated by live-imaging.
      Failure of this reaction in cells over-expressing a dominant negative RAC1-mutant
      (RAC1(T17N)) confirmed that the actin-dynamics of lamellar protrusion is also, in
      these cells, RAC1-dependent. Pretreatment of untransfected cells with 20 microM
      UO126 for 2 h, shown to down-regulate the basic level and to completely inhibit
      cholinergic activation of mitoge-activated kinase (MAPK; erk1/erk2), had no
      effect neither on spontaneous nor on induced lamellar protrusions. When p-JNK,
      whose basic activity is very low and not enhanced by a cholinergic stimulation of
      the cells for up to 30 min, is activated in the presence of 50 microM anisomycin,
      both spontaneous and cholinergically induced lamellar protrusive activity is
      attenuated. These data indicate that the RAC1-controlled cascades promoting
      lamellar protrusion are independent of MAPK activity and partially down-regulated
      by p-JNK.

PMID- 12499847
TI  - Modulation of melanocortin-induced changes in spinal nociception by mu-opioid
      receptor agonist and antagonist in neuropathic rats.
AB  - Co-localization of opioid and melanocortin receptor expression, especially at the
      spinal cord level in the dorsal horn and in the gray matter surrounding the
      central canal led to the suggestion that melanocortins might play a role in
      nociceptive processes. In the present studies, we aimed to determine the effects
      of melanocortins, administered intrathecally, on allodynia, and to ascertain
      whether there is an interaction between opioid and melanocortin systems at the
      spinal cord level. Neuropathic pain was induced by chronic constriction injury
      (CCI) of the right sciatic nerve in rats. Tactile allodynia was assessed using
      von Frey filaments, while thermal hyperlagesia was evaluated in cold water
      allodynia test. In the present experiments, melanocortin receptor antagonist,
      SHU9119 was much more potent than mu-opioid receptor agonist, morphine after
      their intrathecal (i.th.) administration in neuropathic rats. SHU9119 alleviated
      allodynia in a comparable manner to DAMGO, a selective and potent mu-opioid
      receptor agonist. Administration of melanocortin receptor agonist, melanotan-II
      (MTII) increased the sensitivity to tactile and cold stimulation. Moreover, we
      demonstrated that the selective blockade of mu-opioid receptor by cyprodime (CP)
      enhanced antiallodynic effect of SHU9119 as well as pronociceptive action of
      MTII, whereas the combined administration of mu receptor agonist (DAMGO) and
      SHU9119 significantly reduced the analgesic effect of those ligands. DAMGO also
      reversed the proallodynic effect of melanocortin receptor agonist, MTII. In
      conclusion, it seems that the endogenous opioidergic system acts as a functional
      antagonist of melanocortinergic system, and mu-opioid receptor activity appears
      to be involved in the modulation of melanocortin system function.

PMID- 12499848
TI  - Orbitofrontal cortex dysfunction in attention-deficit hyperactivity disorder
      revealed by reversal and extinction tasks.
AB  - Attention-deficit hyperactivity disorder (ADHD) has been considered a mental
      illness in which the frontal lobe is dysfunctional. The orbitofrontal cortex
      (OFC) controls emotional and motivational behaviors which are impaired in ADHD.
      Patients with OFC damage have shown impaired performance in reversal and
      extinction tasks in a simple go/no-go paradigm. We assigned ADHD subjects the two
      tasks to examine a hypothesized dysfunction of OFC. ADHD subjects indeed showed a
      performance deficit in the tasks, supporting OFC dysfunction in ADHD.
      Furthermore, a discriminat analysis using the task performance variables
      correctly classified 89.7% of the participants among ADHD patients and normal
      controls.

PMID- 12499849
TI  - Apoptotic hair cell death after transient cochlear ischemia in gerbils.
AB  - The mechanisms of cochlear hair cell death following exposure to transient inner
      ear ischemia were investigated in gerbils histologically. The animals were
      subjected to ischemic insult by occluding both vertebral arteries for 15 min.
      Hoechst 33342 nuclear staining showed that inner hair cells (IHCs) underwent
      sporadic degeneration via nuclear condensation, which peaked 12 hours after the
      ischemia. Furthermore, nuclear DNA fragmentation was noted by the terminal
      deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)
      biotin nick end labeling method. Transmission electron microscopy revealed
      morphological changes in the IHCs characteristic of apoptosis, including
      karyopyknosis, chromatin condensation. These findings suggest that apoptotic cell
      death is the major process in hair cell degeneration in this animal model.

PMID- 12499850
TI  - Rat strain differences to fluoxetine in striatal Fos-like proteins.
AB  - Humans afflicted with mood disorders respond differently to antidepressant drug
      therapy. Different responses to psychoactive drugs are also observed in rats, and
      specific strains exhibit substantial differences in gene expression following
      synaptic activity. We examined the effects of fluoxetine on the induction of Fos
      like proteins in Long-Evans and Sprague-Dawley rat brains. Fluoxetine elicited a
      strong induction of Fos in the striatum of Long-Evans but not Sprague-Dawley rats
      following acute drug exposure. This effect was specific to fluoxetine as two
      highly selective serotonin reuptake inhibitors, HD-31 and HD-50, as well as
      treatment with fenfluramine failed to replicate the observed differences in Fos.
      These differences in Fos expression between rat strains may represent variability
      in post-receptor pathways that ultimately mediate the therapeutic actions of
      fluoxetine.

PMID- 12499851
TI  - Loss of temporal lobe beta power in young adults with type 1 diabetes mellitus.
AB  - Cognitive defects have been reported in type 1 diabetes mellitus with possible
      correlation to recurrent episodes of hypoglycemia. The purpose of the present
      study was to identify signs of brain dysfunction with quantitative EEG in adults
      with insulin-dependent (type 1) diabetes. Patients (n = 49) with type 1 diabetes
      and controls (n = 51) were recruited. All patients had good glycemic control, no
      diabetic polyneuropathy and a minor history of severe hypoglycaemia. EEG was
      recorded for 15 min following a standardized protocol, power spectra were
      obtained from 236-584 s of artefact-free EEG from each subject and EEG was
      repeated in diabetic patients after 3 and 9 months. The most pronounced finding
      was a loss of fast oscillations (alpha, beta and gamma activity) in both
      posterior temporal regions, with p< 0.001 for beta and p< 0.05 or 0.01 for alpha
      and gamma activity in the diabetes patients. A decrease in beta activity was also
      present bilaterally in the anterior temporal and occipital regions (p< 0.05 or
      0.01). The alpha peak frequency was lower in patients than in controls, with
      reductions bilaterally in the temporo-central regions (p< 0.01). These changes
      were not found to correlate to a previous history of hypoglycaemia. The alpha and
      beta power showed a high test-retest reliability at both 3 and 9 months (0.88
      0.92). The focal decrease in temporal lobe fast activity suggests that these
      brain regions are preferentially affected by type 1 diabetes. This abnormality
      may be related to the mechanism underlying the cognitive dysfunction described in
      diabetes.

PMID- 12499852
TI  - Alteration of functional neuroanatomy of simple object memory in medial temporal
      lobe epilepsy patients.
AB  - Using H2 15O PET, we examined the neuroanatomy associated with a simple form of
      episodic memory in patients with right or left medial temporal lobe epilepsy and
      normal healthy controls. When line drawings of common objects were memorized and
      tested after a 30 min delay, no behavioral difference was found between the
      patient groups and the controls. However, the patients with epilepsy showed
      greater cortical activations than the control group on the side ipsilateral to
      the epileptic focus. rCBF in the anterior thalamic region was enhanced in
      patients relative to the control group. The results showed that long-term
      dysfunction of the medial temporal lobe might reinforce alternative memory
      pathways and recruit a distributed cortical network ipsilateral to their epilepsy
      focus.

PMID- 12499853
TI  - Activation of p38 MAP kinase in the rat dorsal root ganglia and spinal cord
      following peripheral inflammation and nerve injury.
AB  - The intrathecal administration of p38 MAP kinase (p38) inhibitor has been shown
      to reduce hyperalgesia. In the present study, we investigated the activation of
      p38 in the rat dorsal root ganglion (DRG) and spinal cord following peripheral
      tissue inflammation and nerve injury immunohistochemically. Peripheral
      inflammation and chronic constriction injury (CCI) of the sciatic nerve induced a
      significant increase in the percentage of phosphorylated (P-) p38-immunoreactive
      (IR) neurons, primarily small sized ones in bilateral DRGs. In contrast,
      following axotomy, a significant decrease in the percentage of IR neurons was
      observed in ipsilateral DRGs. In addition, a marked increase was observed in the
      number of P-p38-IR microglia in the ipsilateral laminae I-IV and IX of the spinal
      cord following peripheral inflammation, CCI or axotomy. These findings suggest
      that p38 may play an important role in hyperalgesia and the activation of the
      spinal microglia.

PMID- 12499854
TI  - Simultaneous EEG and fMRI of the alpha rhythm.
AB  - The alpha rhythm in the EEG is 8-12 Hz activity present when a subject is awake
      with eyes closed. In this study, we used simultaneous EEG and fMRI to make maps
      of regions whose MRI signal changed reliably with modulation in posterior alpha
      activity. We scanned 11 subjects as they rested with eyes closed. We found that
      increased alpha power was correlated with decreased MRI signal in multiple
      regions of occipital, superior temporal, inferior frontal, and cingulate cortex,
      and with increased signal in the thalamus and insula. These results are
      consistent with animal experiments and point to the alpha rhythm as an index of
      cortical inactivity that may be generated in part by the thalamus. These results
      also may have important implications for interpretation of resting baseline in
      fMRI studies.

PMID- 12499855
TI  - Molecular characterization of voltage-gated sodium channels in human gliomas.
AB  - Voltage-sensitive sodium channels appear to be an electrophysiological hallmark
      of gliomas. However, the expression of channel subtypes is unclear in these
      tumors. In this study different gliomas were investigated for the expression of
      sodium channel subtypes Na(v)1.1, Na(v)1.2, Na(v)1.3, Na(v)1.4, Na(v)1.6, and
      Na(x)(Na(v)2.1) using RT-PCR. At least one subtype of channels could be detected
      in each tumor. High-grade gliomas expressed fewer sodium channel subtypes and
      these at weaker levels than low-grade tumors. Expression of Na(v)1.6, the most
      abundant isoform in the CNS, was almost absent in the gliomas except the
      pilocytic variant. Our study gives clear evidence for a differential expression
      of sodium channel subtypes in gliomas and indicates a predominant expression of
      channels related to malignancy grades.

PMID- 12499856
TI  - Cultural objects modulate reward circuitry.
AB  - Using event-related fMRI we investigated the rewarding properties of cultural
      objects (cars) signaling wealth and social dominance. It has been shown recently
      that reward mechanisms are involved in the regulation of social relations like
      dominance and social rank. Based on evolutionary considerations we hypothesized
      that sports cars in contrast to other categories of cars, e.g. limousines and
      small cars, are strong social reinforcers and would modulate the dopaminergic
      reward circuitry. Twelve healthy male subjects were studied with fMRI while
      viewing photographs of different car classes followed by an attractivity rating.
      Behaviorally sports cars were rated significantly more attractive than limousines
      and small cars. Our fMRI results revealed significantly more activation in
      ventral striatum, orbitofrontal cortex, anterior cingulate and occipital regions
      for sports cars in contrast to other categories of cars. We could thus
      demonstrate that artificial cultural objects associated with wealth and social
      dominance elicit activation in reward-related brain areas.

PMID- 12499857
TI  - Central beta-adrenergic modulation of cognitive flexibility.
AB  - Situational stressors and anxiety impede performance on creativity tests
      requiring cognitive flexibility. Preliminary research revealed better performance
      on a task requiring cognitive flexibility, the anagram task, after propranolol
      (beta-adrenergic antagonist) than after ephedrine (beta-adrenergic agonist).
      However, propranolol and ephedrine have both peripheral and central beta
      adrenergic effects. In order to determine whether noradrenergic modulation of
      cognitive flexibility is a centrally or peripherally mediated phenomenon, we
      compared the effects of propranolol (peripheral and central beta-blocker),
      nadolol (peripheral beta-blocker), and placebo on anagram task performance.
      Solution latency scores for each subject were compared across the drug
      conditions. Anagram solution latency scores after propranolol were significantly
      lower than after nadolol. This suggests a centrally mediated modulatory influence
      of the noradrenergic system on cognitive flexibility.

PMID- 12499858
TI  - Hyperalgesia and blunted morphine analgesia in G protein-gated potassium channel
      subunit knockout mice.
AB  - Our aim was to determine whether G protein-gated potassium (Kir3) channels
      contribute to thermonociception and morphine analgesia. Western blotting was used
      to probe for the presence of Kir3.1, Kir3.2, Kir3.3, and Kir3.4 subunits in the
      mouse brain and spinal cord. Hot-plate paw-lick latencies for wild-type, Kir3.2
      knockout, Kir3.3 knockout, and Kir3.4 knockout mice were measured at 52 degrees C
      and 55 degrees C, following the s.c. injection of either saline or 10 mg/kg
      morphine. Paw-lick latencies for Kir3.4 knockout mice were similar to those of
      wild-type mice, consistent with the restricted expression pattern of Kir3.4
      subunit in the mouse brain. In contrast, Kir3.2 knockout and Kir3.3 knockout mice
      displayed hyperalgesia at both temperatures tested, and both Kir3.2 knockout and
      Kir3.3 knockout mice displayed shorter paw-lick latencies following morphine
      administration, with Kir3.2 knockout mice exhibiting the more dramatic phenotype.
      Kir3.2/Kir3.3 double knockout mice displayed a greater degree of hyperalgesia
      than either the Kir3.2 knockout or Kir3.3 knockout mice, while performing
      similarly to Kir3.2 knockout mice following morphine administration. We conclude
      that G protein-gated potassium channels containing Kir3.2 and/or Kir3.3 play a
      significant role in responses to moderate thermal stimuli. Furthermore, the
      activation of Kir3 channels containing the Kir3.2 subunit contributes to the
      analgesia evoked by a moderate dose of morphine. As such, receptor-independent
      Kir3 channel agonists may represent a novel and selective class of analgesic
      agent.

PMID- 12499859
TI  - Functional expression of a mammalian olfactory receptor in Caenorhabditis
      elegans.
AB  - The olfactory system in both vertebrates and invertebrates can recognize and
      distinguish thousands of chemical signals. Olfactory receptors are responsible
      for the early molecular events in the detection of volatile compounds and the
      perception of smell. Recently, candidate olfactory receptor genes have been
      identified in several organisms, but their characterization is far from been
      completed due to the difficulty to functionally express them in heterologous
      systems. To circumvent such difficulty, we expressed a mammalian olfactory gene,
      rat I7, in the nematode. We generated transgenic worms expressing I7 in AWA or
      AWB chemosensory neurons and performed behavioural assays using different
      concentrations of the rat I7 receptor agonist octanal. Pure octanal was repellent
      for wild-type worms whereas a 1:10 dilution was attractant. Expression of I7 in
      AWB neurons counteracted the volatile attraction to diluted octanal observed in
      control wild-type worms. Furthermore, expression of I7 in AWA neurons
      counteracted the volatile avoidance to pure octanal observed in wild-type worms.
      These results indicate that it is possible to functionally express mammalian
      olfactory receptors in providing a research tool to efficiently search for
      specific olfactory receptor ligands and to extend our understanding of the
      molecular basis of olfaction.

PMID- 12499860
TI  - Luminance and chromatic contrast sensitivity in dyslexia: the magnocellular
      deficit hypothesis revisited.
AB  - The hypothesis of a magnocellular channel deficit in dyslexia was tested.
      Subjects were 10-year-old dyslexics and normal readers. Psychophysical thresholds
      for luminance and chromatic contrasts were estimated using black and white and
      red and green sinusoidal gratings of various spatial frequencies, presented in
      static and dynamic conditions (drift and reversal). Significant group differences
      were found for luminance contrast, with a higher sensitivity in dyslexics. No
      group differences were obtained for chromatic contrast. High luminance contrast
      sensitivity correlated with low reading and writing skills. The typical finding
      of an increase contrast sensitivity to low spatial frequency gratings, due to
      their dynamic presentations, was absent in dyslexics. The results provide support
      for the magnocellular deficit hypothesis. The pattern of this deficit, however,
      is much more complex than that emerging from previous research.

PMID- 12499861
TI  - Exercise increases mRNA levels for adhesion molecules N-CAM and L1 correlating
      with BDNF response.
AB  - In situ hybridization was used to evaluate whether long-term moderate locomotor
      exercise, which up-regulates BDNF and TrkB levels in the spinal gray matter of
      the adult rat, similarly influences the expression of the cell adhesion molecules
      N-CAM and L1. Exercise doubled the level of N-CAM mRNA hybridization signal in
      the lumbar spinal gray. The increase in L1 mRNA was less consistent. N-CAM mRNA
      levels slightly increased in the white matter. BDNF mRNA levels also increased in
      cells of the ventral horn and the white matter due to the exercise. These results
      suggest that exercise-induced rearrangements of the spinal network involve N-CAM,
      L1 and BDNF, crucial in different aspects of synaptic plasticity and synapse
      formation.

PMID- 12499862
TI  - Imitation without awareness.
AB  - Imitation is a characteristic but little-understood function of the human brain
      and of some higher animals. The direct matching hypothesis suggests that a
      specialised brain circuit is able to extract and directly copy the motor commands
      of another person's observed actions. Here we investigate how conscious people
      are of this kind of imitation. We first showed that imitation reactions are
      faster than simple visual reaction times, consistent with a direct matching
      circuit in the CNS. We next compared the perceived time of imitation reactions in
      17 healthy subjects with other kinds of actions. We found a significant delay in
      subjects' awareness of their own imitation reactions. Thus, while imitation
      reactions are unusually fast, subjects are not aware of this. The brain's direct
      matching circuit for imitation partly bypasses conscious awareness.

PMID- 12499863
TI  - Temporal pole hypometabolism may be linked to a reduction of grey matter in
      temporal lobe epilepsy.
AB  - In order to gain further insight into the pathophysiology of temporal pole
      hypometabolism, we decided to perform a voxel-based automated analysis of
      structural MRI in epileptic patients with or without temporal pole
      hypometabolism. After fully automated segmentation of cerebral grey matter from
      structural T1-weighted MRI scans, we applied the automated technique of
      statistical parametric mapping (SPM) to the analysis of grey matter of nine
      control subjects, and 18 patients with right medial temporal lobe epilepsy with
      (n = 13) or without (n = 5) significant temporal pole hypometabolism. Group
      comparisons between subject controls and epileptic patients with temporal pole
      hypometabolism showed a reduction of grey matter located into the superior part
      of the right temporal pole, the right hippocampus and the left parahippocampal
      gyrus. Epileptic patients without temporal pole hypometabolism did not exhibit
      temporal pole grey matter abnormalities. These findings suggest that a reduction
      of temporal pole neocortical grey matter might contribute to temporal pole
      hypometabolism in temporal lobe epilepsy.

PMID- 12499864
TI  - Transient osmotic stress facilitates mutant huntingtin aggregation.
AB  - Human neuroblastoma SH-SY5Y cell lines stably expressing mutant truncated
      huntingtin with 82 (mutant) glutamine repeats (N63-82Q) were briefly exposed to
      hyperosmotic conditions which decrease cell volume and therefore transiently
      increased the concentration of N63-82Q, as well as activating specific stress
      induced pathways. Transient hyperosmotic treatment significantly increased the
      number of cells with aggregates. When the N63-82Q cells were subsequently
      returned to iso-osmotic medium after the treatment, the number of cells with
      aggregates remained constant up to 12 h. However, between 12 and 24 h another
      significant increase in aggregate frequency was observed, with approximately 55%
      of the cells containing aggregates after 24 h. This may be due in part to the
      formation of microaggregates during hyperosmotic conditions that act as seeds for
      the aggregate formation. Further, treatment of cells with geldanamycin, which
      activates a heat shock response, significantly attenuated the hyperosmotic
      induced increase in aggregate formation.

PMID- 12499865
TI  - Localization of Nav1.5 sodium channel protein in the mouse brain.
AB  - Na(v)1.5 or SCN5A is a member of the voltage-dependent family of sodium channels.
      The distribution of Na(v)1.5 protein was investigated in the mouse brain using
      immunohistochemistry. Immunostaining with a Na(v)1.5-specific antibody revealed
      that Na(v)1.5 protein was localized in certain distinct regions of brain
      including the cerebral cortex, thalamus, hypothalamus, basal ganglia, cerebellum
      and brain stem. Notably, we found that Na(v)1.5 protein co-localized with
      neurofilaments and clustered at a high density in the neuronal processes, mainly
      axons. These results suggest that Na(v)1.5 protein may play a role in the
      physiology of the central nervous system (generation and propagation of
      electrical signals by axons).

PMID- 12499866
TI  - A new experimental model in rats for study of the pathophysiology of subarachnoid
      hemorrhage.
AB  - A new experimental model of subarachnoid hemorrhage (SAH) in rats is described. A
      needle was stereotaxically placed in the prechiasmatic cistern and 300, 250 or
      200 microl of blood was injected manually, keeping the intracranial pressure
      (ICP) at the mean arterial blood pressure (MABP) level. An acceptable mortality
      was observed only after injection of 200 microl of blood. In this group, MABP and
      ICP increased immediately after SAH, but soon approached baseline levels. The
      subarachnoid blood was mainly distributed in the basal cisternal system and its
      estimated volume was about 95% of the amount injected. This new model resembles
      clinical SAH, is very reproducible, easy to use and seems to be a suitable model
      for studies of the pathophysiology of SAH.

PMID- 12499867
TI  - Phasic visual alertness in Alzheimer's disease and ageing.
AB  - An individual's ability to see and react quickly to a target stimulus is enhanced
      if they are alerted to the arrival of this target by a stimulus that occurs just
      prior in time to it. This alerting effect is thought to occur due to a phasic
      increase in alertness mediated by noradrenergic activity. In Alzheimer's disease
      (AD) there is a dysfunction in the noradrenergic system resulting in a decrease
      in central levels of noradrenaline. We therefore predicted that patients with AD
      would not be able to benefit from the prior stimulus to the same extent as that
      seen in healthy older adults and thus would have a reduced or abolished alerting
      effect. We measured reaction times to respond to a visual target that could be
      preceded (by 200 ms) by a visual alerting cue, in 17 patients with Alzheimer's
      disease, 19 age-matched controls and 13 younger controls. We found that the
      alerting cue significantly decreased the reaction times for both the young and
      old controls, but that this cue had no effect upon the reaction times for those
      with AD. This marked inability to increase phasic alertness in AD may contribute
      to the everyday problems faced by these patients, and may provide a simple tool
      to aid diagnosis and disease progression.

PMID- 12499868
TI  - Deficits in brain serotonin synthesis in a genetic mouse model of
      phenylketonuria.
AB  - Although hyperphenylalaninemia causes neurological disturbances and mental
      retardation, the neuropathological effects of phenylalanine excess are still
      poorly understood. Brain serotonin depletion may play a major role in such
      disturbances and is a possible target for feasible pharmacotherapies. In the
      present study, we investigated hyperphenylalaninemia-related brain serotonin
      depletion using a genetic mouse model of phenylketonuria, the Pah(enu2) mutant.
      Mutant mice showed severe depletion of whole brain serotonin, a mild reduction in
      the brain level of tryptophan, its amino acid precursor, and major deficits in
      the brain level of 5-hydroxytryptophan, the second rate-limiting factor in
      serotonin synthesis. These results suggest that interference with brain 5
      hydroxytryptophan synthesis may be the major cause of serotonin deficits in
      hyperphenylalaninemia.

PMID- 12499869
TI  - Brief exposure to NaCl during early postnatal development enhances adult intake
      of sweet and salty compounds.
AB  - Taste acceptance involves both innate and acquired components. We observed an
      increased acceptance of salty and sweet solutions in adult rats whose tongues had
      been exposed to an NaCl-enriched milk formula during one day of early postnatal
      development. This behavioral effect was associated with changes in the
      norepinephrine system of the basolateral amygdala. No other changes in behavior,
      food intake, body weight, blood or metabolic parameters of the NaCl-exposed adult
      rats were identified. The data suggest a causal relationship between NaCl taste
      exposure, low content of amygdala norepinephrine cells and enhanced intake of
      sweet and salty compounds by adult rats. They also raise the question of the
      extent to which similar phenomena may occur during early human infant feeding.

PMID- 12499870
TI  - Perceptual and response bias in visuospatial neglect due to frontal and parietal
      repetitive transcranial magnetic stimulation in normal subjects.
AB  - Recently some authors have challenged the conventional association of directional
      motor neglect with damage of frontal structures, showing that pure sensory
      perceptual neglect (classically associated with parietal lesion) can follow
      damage of right frontal cortex. The aim of the present study was to assess the
      type of defect in visuo-spatial attention consequent upon a virtual frontal or
      parietal lesion induced by transcranial magnetic stimulation in normal subjects.
      To this purpose eleven subjects performed a visuo-spatial task requiring
      judgement about the length of the two segments of asymmetrically bisected
      horizontal lines, presented for 50 ms on a computer monitor. After each visual
      stimulus, subjects made a binary forced choice decision according to two
      different response conditions: A and B. In condition A, they had to name (right
      or left) the longer segment and in B the shorter segment of the line. The task
      was given in baseline condition and during repetitive transcranial magnetic
      stimulation. Trains of 10 stimuli at 25 Hz of frequency were applied over right
      frontal premotor and right posterior parietal areas, synchronously with visual
      stimuli. Parietal and frontal magnetic stimulation gave rise to significant
      perceptual bias as compared to baseline performance (i.e. subjects made opposite
      errors in the two response conditions). No significant response bias (i.e. the
      tendency to name the same side of the line in the two response conditions) was
      induced by magnetic stimulation on parietal and frontal sites. The present study
      highlights both the relevant contribution of frontal cortex in the determinism of
      neglect and the predominant role of sensory perceptual factors in parietal and
      frontal neglect.

PMID- 12499872
TI  - Post-apoplectic reorganization of cortical areas processing passive movement and
      tactile stimulation--a neuromagnetic case study.
AB  - Magnetoencephalography (MEG) was used in a patient with right centro-parietal
      stroke to investigate the cortical processing of tactile pneumatic stimulation
      and passive movement of the impaired left and unaffected right-hand index finger.
      Source localization of somatosensory evoked magnetic fields (SEF) recorded 2
      weeks after infarction demonstrated a spatial displacement of the contralateral
      SI generators in the affected hemisphere. The distance between SI sources
      activated by either stimulation technique was noticeably enlarged in comparison
      to the left hemisphere and to previous data from 12 healthy subjects. Follow-up
      MEG after 6 months revealed a closer spatial arrangement of the two modality
      specific SEF generators and a diminution of the interhemispheric asymmetry of
      proprioception-related SI sources. The topographical alterations were accompanied
      by clear clinical improvement of both joint position sense and tactile sensation.
      The occurrence of ipsilateral SI activity following passive movement of only the
      impaired index finger might suggest a disinhibition of subthreshold,
      transcallosal excitatory pathways.

PMID- 12499871
TI  - Thapsigargin blocks STP and LTP related calcium enhancements in hippocampal CA1
      area.
AB  - Multiple calcium signaling pathways, including intracellular calcium release that
      is mediated by inositol triphosphate (IP3) or ryanodine calcium store receptors,
      seem to be involved in CA1 hippocampal synaptic plasticity. We have addressed the
      role of dendritic calcium release in short- and long-term potentiation (STP and
      LTP) using thapsigargin, which depletes intracellular calcium stores. Measuring
      Fura-2 calcium signals and extracellular field potentials, we have found that
      thapsigargin did not affect single pre-tetanus calcium transients but reduced
      tetanically evoked calcium changes. The latter effect prevented the formation of
      short- and long-lasting calcium enhancements. These results are consistent with
      the idea that intracellular calcium release is not involved in baseline synaptic
      transmission but is essential for those forms of synaptic plasticity.

PMID- 12499873
TI  - Activated T cells mediate direct blood-brain barrier endothelial cell death and
      dysfunction.
AB  - Neuro-inflammation is characterized by immune cell infiltration across the blood
      brain barrier, a process instrumental in neuronal cell death. In neuro
      inflammation the blood-brain barrier is also damaged and the consequences of
      activated lymphocytes on the integrity of the blood-brain barrier is not well
      characterized. Utilizing an blood-brain barrier model we demonstrate that
      endothelial cell viability and barrier integrity are directly altered following
      lymphocyte exposure. The effect of activated lymphocytes is cell number
      dependent, mostly mediated by direct contact, and is not associated with the pro
      inflammatory cytokine TNF-alpha. For the successful treatment of neuro
      inflammatory disease, intervention of this direct effect at the blood-brain
      barrier is warranted.

PMID- 12499874
TI  - Evaluation of the role of P-glycoprotein in inflammation induced blood-brain
      barrier damage.
AB  - In this study we evaluated the role of the multi-drug transporter p-glycoprotein
      (Pgp) in the process of activated T lymphocyte-mediated blood-brain barrier
      dysfunction as described previously. Lymphocyte exposure induced significant
      endothelial cell death and there was an elevation of the expression of Pgp in the
      surviving cells. Inhibition of Pgp function using the antibody MRK16 and
      verapamil displayed a dose-dependent prevention of T cell mediated endothelial
      cell death and barrier breakdown. These data suggest that the activity of Pgp at
      the blood-brain barrier may play a role in lymphocyte induced barrier cell damage
      and a role as a possible survival mechanism to prevent further endothelial cell
      death in later stages of inflammation.

PMID- 12499876
TI  - Low recurrence rate of hepatocellular carcinoma after liver transplantation:
      better patient selection or lower immunosuppression?

PMID- 12499875
TI  - Organ donors with positive viral serology or malignancy: risk of disease
      transmission by transplantation.

PMID- 12499877
TI  - Improved myocardial function with the addition of pinacidil to custadiol.
AB  - BACKGROUND: This study investigates the efficacy of pinacidil, an adenosine
      triphosphate-sensitive potassium (KATP) channel opening agent, added to custadiol
      solution on myocardial protection during deep hypothermia and prolonged global
      ischemia on isolated rat hearts. METHODS: After 20 minutes of stabilization, 24
      rats were divided into two groups. In group I (n=12), hearts were arrested with
      cold (4 degrees C) custadiol solution containing 50 micromol/L of pinacidil and
      subsequently dipped into the same solution for 120 minutes at 4 degrees C. Group
      I hearts were perfused with low-flow pinacidil-custadiol (PC) solution during the
      ischemic period. Group II (n=12) hearts, after the stabilization period, were
      arrested with cold custadiol solution only, then subsequently dipped and perfused
      with the same solution for 120 minutes at 4 degrees C. All hearts were reperfused
      with Krebb's-Henseleit solution at 37 degrees C for 60 minutes. Hemodynamic
      parameters (peak systolic pressure, end diastolic pressure, maximum rate of
      increase of left ventricular pressure [+dP/dt], ischemic contracture, and
      coronary sinus flow) were recorded at the end of the stabilization period and at
      10-minute intervals during the reperfusion period. Biochemical data (creatine
      kinase [CK-MB] washout and troponin I [cTnI] levels) were compared between the
      two groups. RESULTS: There was no significant difference in any hemodynamic or
      biochemical parameters between the two groups during the stabilization period.
      The peak systolic pressure, +dP/dt, ischemic contraction amplitude, and coronary
      flow values were significantly higher in group I ( P<0.05) compared with group II
      during reperfusion. End diastolic pressures as well as CK-MB and cTnI levels were
      lower in the pinacidil-treated group, which is consistent with improved
      functional recovery during the reperfusion period. CONCLUSION: The addition of
      pinacidil to the preservation solution, custadiol, improves myocardial recovery
      after deep hypothermia and prolongs ischemia.

PMID- 12499878
TI  - Characterization of fibroblasts from rejecting tissue: the hyaluronan production
      is increased.
AB  - BACKGROUND: Interstitial edema of rejecting tissue can be partly attributed to
      the local accumulation of hyaluronan, which has strong water-binding capacity.
      The aim of the present study was to isolate fibroblasts from rejecting tissue and
      compare them, in terms of hyaluronan production and proliferation rate, with
      fibroblasts obtained from nontransplanted tissue. Furthermore, the fibroblast
      response to various cytokines involved in the rejection process was studied.
      METHODS: Fibroblasts were isolated from normal rat heart tissue and from cardiac
      allografts undergoing rejection. The various preparations were characterized with
      regard to hyaluronan production (radiometric assay) and cell proliferation ( H
      thymidine incorporation). In addition, the effects of tumor necrosis factor (TNF)
      alpha, interferon (IFN)-gamma, and interleukin (IL)-2 on these parameters were
      studied. RESULTS: Fibroblasts isolated from rejecting hearts displayed strongly
      up-regulated hyaluronan production and proliferation rate as compared with
      fibroblasts obtained from normal tissue. In the presence of TNF-alpha, the
      proliferation of nonconfluent cells was augmented, whereas in confluent cultures
      of fibroblasts from rejecting tissue, the proliferation was inhibited. IFN-gamma
      stimulated both hyaluronan secretion and proliferation in confluent fibroblasts
      from rejecting hearts but had no effect on fibroblasts from normal tissue. IL-2,
      finally, reduced the hyaluronan production of nonconfluent cells. CONCLUSIONS:
      The activation of fibroblasts is increased in rejecting tissue. As a result, the
      hyaluronan concentration is elevated which, in vivo, contributes to the formation
      of an interstitial edema and a subsequently increased tissue pressure. Several
      cytokines present at rejection are involved also in the regulation of fibroblast
      activity.

PMID- 12499879
TI  - alpha-Melanocyte-stimulating hormone protects the allograft in experimental heart
      transplantation.
AB  - BACKGROUND: With the increasing need for organ transplantation and the use of
      "marginal" organs, novel approaches are sought to increase the efficiency and
      survival of transplanted tissue. We tested the idea that treatment with the anti
      inflammatory peptide, alpha-melanocyte-stimulating hormone (alpha-MSH), an
      endogenous hormone that does not cause marked immunosuppression but does reduce
      reperfusion injury, may protect allografts and prolong their survival. METHODS:
      Donor cardiac grafts (Brown Norway) were transplanted heterotopically into the
      abdomen of recipient (Lewis) rats. Treatments consisted of intraperitoneal
      injections of Nle DPhe -alpha-MSH (NDP-alpha-MSH) or saline from the time of
      transplantation until sacrifice or spontaneous rejection. Allografts were removed
      on day 1, day 4, or at the time of rejection and examined for histopathology and
      expression of molecules prominent in reperfusion injury, transplant rejection,
      and apoptosis. RESULTS: NDP-alpha-MSH treatment caused a significant increase in
      allograft survival and a marked decrease in leukocyte infiltration. Expression of
      molecules such as endothelin 1, chemokines, and adhesion molecules, which are
      involved in allograft rejection, was significantly inhibited in NDP-alpha-MSH
      treated rats. CONCLUSIONS: The results indicate that protection of the allograft
      from early injury with alpha-MSH can postpone rejection. Addition of this early
      protection with the peptide to usual treatment with immunosuppressive agents may,
      therefore, improve success of organ transplants.

PMID- 12499880
TI  - Prevention of autoimmune diabetes by FTY720 in nonobese diabetic mice.
AB  - BACKGROUND: FTY720 prevents allograft rejection with remarkable potency without
      inducing generalized immunosuppression. We determined the effect of FTY720 on
      development of autoimmune diabetes in nonobese diabetic (NOD) mice. METHODS: NOD
      mice were given FTY720 (0.5 mg/kg, orally) five times per week starting from 4
      weeks of age. RESULTS: Daily FTY720 prevented development of diabetes in 15 of 16
      treated mice, whereas 70% of untreated NOD mice became diabetic by 35 weeks of
      age. Withdrawal of FTY720 at 35 weeks of age led to development of diabetes
      within 2 weeks in five mice, whereas the remaining mice maintained diabetes-free
      conditions for up to 44 weeks of age. No side effect of the drug was seen
      throughout the treatment period. FTY720 also prevented cyclophosphamide-induced
      diabetes in NOD mice. CONCLUSIONS: FTY720 is a safe and benign therapeutic agent
      that may be used chronically in prediabetic individuals.

PMID- 12499881
TI  - Human islet transplantation from pancreases with prolonged cold ischemia using
      additional preservation by the two-layer (UW solution/perfluorochemical) cold
      storage method.
AB  - BACKGROUND: A two-layer (University of Wisconsin solution/perfluorochemical
      [UW/PFC]) cold-storage method delivers sufficient oxygen to the pancreas during
      preservation and restores the ischemically damaged pancreas. In this study, we
      determined whether the additional preservation by the two-layer method could
      improve islet recovery from human pancreases with prolonged cold storage in UW.
      METHODS: Human pancreases were procured from cadaveric organ donors and preserved
      by the two-layer method (UW/PFC) for 2.9+/-0.7 hours (mean+/-SEM) at 4 degrees C
      after 11.8+/-1.5 hours of cold storage in UW (UW/PFC group, n=7), or by cold UW
      alone for 11.3+/-0.3 hours (UW group, n=14). The selected pancreases met the
      criteria of having at least 10 hours of cold storage in UW. All were processed by
      using a standard protocol of Liberase perfusion with Pefabloc by way of the duct,
      gentle mechanical dissociation, and Ficoll gradient purification. Transplanted
      islets were selected with the criteria of the Edmonton protocol (>5,000 islet
      equivalents [IE]/kg recipient body weight). RESULTS: The islet recovery was
      significantly increased in the UW/PFC group compared with the UW group (349.2+/
      44.1 x 10 and 214.0+/-31.0 x 10 IE, respectively; <0.05). This resulted in islet
      yields of 4.6+/-1.0 x 10 IE/g of pancreas in the UW/PFC group compared with 2.0+/
      0.3 x 10 IE/g of pancreas in the UW group ( <0.05). Five of 7 cases (71%) in the
      UW/PFC group and 5 of 14 cases (36%) in the UW group were transplanted. The islet
      grafts in the UW/PFC group improved the ability of glycemic control and decreased
      exogenous insulin administration in all recipients. CONCLUSIONS: Improvements in
      methods to preserve and recover ischemically damaged human pancreases before
      islet isolation and transplant could be extremely beneficial to the field of
      clinical islet transplantation. This preliminary study shows that additional
      short preservation by the two-layer (UW/PFC) cold-storage method can
      significantly improve islet recovery and increase opportunities of islet
      transplantation from human pancreases after prolonged cold ischemia.

PMID- 12499882
TI  - Erythropoiesis after nonmyeloablative stem-cell transplantation is not impaired
      by inadequate erythropoietin production as observed after conventional allogeneic
      transplantation.
AB  - BACKGROUND: It is now well established that after conventional allogeneic
      hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is
      impaired because erythropoietin (Epo) production remains inadequate for prolonged
      periods of time. However, erythropoietic reconstitution after nonmyeloablative
      SCT (NMSCT) has never been characterized. METHODS: Twelve patients received a
      nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation
      (TBI) alone (n=6), 2 Gy TBI and fludarabine (n=3), or cyclophosphamide and
      fludarabine (n=3), followed by transplantation of allogeneic peripheral blood
      stem cells. Graft-versus-host-disease (GvHD) prophylaxis was carried out with
      mycophenolate mofetil (from day -1 to day 28) plus cyclosporine (from day -1 to
      day 120 or longer in case of chronic GvHD). Erythropoiesis was quantitated by
      soluble transferrin receptor (sTfR) levels, and the adequacy of Epo production
      was evaluated by the observed-to-predicted Epo ratio (O/P Epo). RESULTS: Mean
      sTfR levels decreased following the conditioning regimen but remained well within
      the normal range throughout the posttransplant period. The O/P Epo ratio
      presented an initial surge quite similar to that observed after conventional
      conditioning. Thereafter, the O/P Epo ratio normalized rapidly, and Epo levels
      remained adequate during the whole observation period. CONCLUSION: Contrarily to
      what is observed after myeloablative transplant, Epo levels remained adequate
      after NMSCT, resulting in normal erythropoiesis. These results suggest that the
      administration of erythropoietin therapy (rHuEpo) could be less effective after
      NMSCT than after conventional allogeneic transplant.

PMID- 12499883
TI  - Safe administration of a humanized murine antibody after anaphylaxis to a
      chimeric murine antibody.
AB  - BACKGROUND: Basiliximab and daclizumab are potent and relatively safe
      immunosuppressive induction agents used in transplantation. These chimeric or
      humanized monoclonal antibodies, respectively, act by binding to the alpha chain
      of interleukin-2 receptors on activated T lymphocytes. Herein, the authors
      describe successful transplant induction therapy with a humanized murine antibody
      in a patient with a history of anaphylaxis to a chimeric murine antibody.
      METHODS: The authors report a 42-year-old woman who received a dose of
      basiliximab without adverse reaction before an anticipated renal transplant that
      was canceled. Two weeks later, she received a second dose of basiliximab. Within
      10 min of receiving the second dose, she developed chest tightness, shortness of
      breath, tongue swelling, diffuse pruritic rash, and skin flushing. RESULTS: The
      authors hypothesized that her anaphylaxis was mediated by immunoglobulin (Ig) E
      antibodies to basiliximab. Consistent with this hypothesis, intradermal
      administration of a 1:100 dilution of basiliximab induced a 10 x 10-mm flare. The
      authors sought to find an alternative immunosuppressive agent for this patient.
      The patient elicited prick and intradermal skin testing responses to horse and
      rabbit polyclonal antithymocyte antibody preparations. However, she mounted
      neither a prick nor an intradermal response to daclizumab. The patient was
      administered daclizumab without any adverse effects. CONCLUSIONS: The negative
      skin test and safe administration of daclizumab is surprising because the
      similarity of these hybrid antibodies would have predicted similar IgE
      responsiveness and clinical outcome. The authors propose that patients who
      develop anaphylaxis to basiliximab or other chimeric antibodies may be candidates
      for treatment with a humanized antibody preparation such as daclizumab in the
      presence of a negative skin test to the humanized agent.

PMID- 12499884
TI  - Use of heparin and protamine sulfate during laparoscopic donor nephrectomy.
AB  - BACKGROUND: Our aim was to evaluate the necessity of heparin and protamine
      administration during laparoscopic donor nephrectomy. METHODS: Data from 52
      consecutive living-related laparoscopic donor nephrectomies performed at
      University of California Los Angeles between August 1999 and August 2001 were
      used for this analysis. For the purpose of this analysis, the patients were
      divided into three cohorts: group A received both heparin and protamine; group B
      received heparin only; and group C received neither. Intraoperative blood loss,
      length of admission, recipient creatinine at follow-up, and intraoperative and
      postoperative complications were compared between the groups. Statistical
      analysis was performed using a two-tailed test. RESULTS: There were no
      significant differences between the groups with regard to patient age and gender.
      Intraoperative blood loss did not differ between group B (99+/-73 mL) and group C
      (82+/-54 mL) ( =0.4). None of the patients required blood transfusion. No graft
      loss occurred in any group. Length of hospital stay, excluding any preoperative
      days, was similar (2.8+/-0.7, 2.9+/-1.6, and 2.5+/-0.8 days, for groups A, B, and
      C, respectively, ( >0.05). No systemic thromboembolic complications were noted in
      any of the groups. One patient in group B was converted to an open procedure
      because of a difficult dissection unrelated to heparin administration. The mean
      recipient creatinine levels at follow-up in the recipients of kidneys from groups
      A, B, and C were not significantly different (1.1, 1.3, and 1.3; >0.05) through
      the extended follow-up period of 691, 286, and 97 days, respectively.
      CONCLUSIONS: According to our experience, there is no apparent benefit in the
      administration of heparin alone or in the administration of protamine sulfate to
      reverse heparin anticoagulation during laparoscopic donor nephrectomy if heparin
      is given. This is not only in terms of bleeding complications but is also true in
      regard to recipient renal function through the follow-up period. It is important
      to note that our warm ischemic times were less than 2 minutes, because longer
      warm ischemic times may make the use of heparin a more important consideration.
      This is the first time that these questions have been studied in the laparoscopic
      donor nephrectomy population.

PMID- 12499885
TI  - Early steroid withdrawal in renal transplantation with tacrolimus dual therapy: a
      pilot study.
AB  - BACKGROUND: With tacrolimus-based immunosuppression, it appears safe to withdraw
      steroids 3 to 6 months after renal transplantation. We hypothesized whether
      steroids could also be safely withdrawn early after transplantation. METHODS:
      Sixty-two patients (first or second transplant, with no previous immunological
      failure, and current panel reactive human leucocyte antigen [HLA] antibodies
      [PRA]<50%), treated with tacrolimus, were prospectively randomized to stop
      steroids (10 mg prednisolone) after day 7 posttransplantation (stop group [STOP],
      n=28) or to gradually wean off steroids in 3 to 6 months (tapering group [TAP],
      n=34). Analyses were performed on an intention-to-treat basis. RESULTS: After a
      median follow-up of 2.7 years, patient and graft survival were 97 and 90% and
      comparable between both groups (P =0.11 and P=0.13, respectively). The incidence
      of acute rejection was 29 (STOP) versus 33% (TAP) ( P=0.30). The time to the
      first rejection was a median of 35 days (STOP) versus 11 days (TAP) ( =0.19). The
      severity of the rejections (1997 Banff classification) was comparable (P =0.57).
      Creatinine clearance and proteinuria were similar (P >0.70). The incidence of
      infections was comparable ( P>0.10). The incidence of new-onset diabetes
      mellitus, defined as the use of antidiabetic medication, was 8.0 (STOP) versus
      30.3% (TAP) (P =0.04). All cases occurred in the STOP group after 1 year, while
      all cases occurred in TAP in the first 4 months ( P<0.001). CONCLUSIONS: Compared
      with tapering in 3 to 6 months, stopping steroids 1 week posttransplantation
      results in comparable patient and graft survival and in a similar incidence of
      acute rejections. The incidence of new-onset diabetes may be reduced. The
      immunosuppressive benefit of adding 10 mg prednisolone to tacrolimus seems to be
      limited.

PMID- 12499886
TI  - Captopril enhances transforming growth factor (TGF)-beta1 expression in
      peripheral blood mononuclear cells: a mechanism independent from angiotensin
      converting enzyme inhibition? A study in cyclosporine-treated kidney-transplanted
      patients.
AB  - BACKGROUND: Angiotensin (Ang) II blockade has been shown to prevent the
      development of renal injury in immunologically mediated diseases, but the
      mechanism whereby it exerts its protective effect has not been clearly defined.
      Transforming growth factor (TGF)-beta1 is a multifunctional cytokine with a
      potent immunomodulatory activity that has the potential to counteract many of the
      pro-inflammatory effects apparently evoked by the activation of renin-angiotensin
      system (RAS) in immune cells. METHODS: We set up an ex vivo and in vitro model to
      evaluate the effect of the angiotensin converting enzyme inhibitor (ACEi)
      captopril on the gene and protein expression of TGF-beta1 in human peripheral
      blood mononuclear cells (PBMC). RESULTS: In 20 kidney transplant recipients
      chronically treated with cyclosporine (CsA), 1-month treatment with captopril
      increased TGF-beta mRNA by 120% and TGF-beta1 protein release by 140% upon
      stimulation of PBMC with phytohemagglutinin (PHA) and phorbol myristate acetate
      (PMA) ( P<0.01). PBMC from healthy controls, when exposed in vitro to 5 microM
      captopril, showed a significant increase of TGF-beta1 release, whereas the ACEi
      enalapril failed to modify the expression of the cytokine. Ang II (100 pM)
      strongly inhibited TGF-beta1 synthesis by PBMC, and such effect was completely
      abolished by the addition of 200 ng/mL CsA, as well as by 1 micrpM losartan.
      Thus, captopril enhances TGF-beta1 gene and protein expression by PBMC by way of
      a mechanism independent, at least in part, from ACE inhibition, while CsA
      abrogates the inhibition of TGF-beta1 expression induced by Ang II. CONCLUSION:
      Collectively, these findings support the utility of combined treatment with
      captopril and CsA in the multitherapeutic management of organ transplant and,
      possibly, a strategy to decrease the dose of the calcineurin inhibitor in kidney
      transplant recipients.

PMID- 12499887
TI  - Renal transplantations performed using non-heart-beating organ donors: going back
      to the future?
AB  - BACKGROUND: As more expanded-criteria organ donors are used to bridge the
      widening gap between organ supply and demand, non-heart-beating (NHB) donors will
      become increasingly important. The purpose of this study was to analyze renal
      transplant outcomes using this source of cadaveric (CAD) organs and compare the
      results with heart-beating organ sources. METHODS: Data from 98,698 adult CAD
      renal transplant recipients and 34,531 living donor renal transplant recipients
      registered in the U. S. Renal Data System database between January 1993 and June
      2000 were analyzed. Kaplan-Meier survival curves were used to compare graft and
      patient survival rates between NHB, CAD, and living donor transplant recipients.
      Cox proportional hazards models were used to identify risk factors for NHB donor
      recipients, while adjusting for potential confounding variables. RESULTS:
      Recipients of NHB donor organs experienced nearly twice the incidence of delayed
      graft function (DGF) compared with heart-beating donors (42.4% vs. 23.3%,
      respectively). NHB donor transplants experienced comparable allograft survival
      when compared with CAD transplants at 6 years (73.2% vs. 72.5%, respectively;
      P=NS); patient survival was greater at 6 years for NHB compared with CAD renal
      transplant recipients (80.9% vs. 77.8%, respectively; P=NS). Significant factors
      for allograft loss for NHB donor organ recipients included the following: organ
      used for repeat transplants; DGF; donor age older than 35 years; and head trauma
      as a cause of initial injury (relative risk 2.74, 1.90, 1.78, and 1.41,
      respectively). CONCLUSIONS: Although exhibiting elevated DGF rates, allograft and
      patient survival rates of transplants from NHB donor sources are equivalent to
      those from conventional CAD sources. Donor age, recipient transplant number,
      female recipient, mechanism of injury, and DGF were the most pertinent variables
      leading to poor outcomes.

PMID- 12499888
TI  - Causes of mortality beyond 1 year after primary pediatric liver transplant under
      tacrolimus.
AB  - BACKGROUND: Success of pediatric liver transplantation has improved
      significantly. Most posttransplant deaths occur early and are related to surgical
      complications or recipient status at the time of transplantation. The causes of
      mortality beyond the first year have not been well described. METHODS: Three
      hundred twenty-six pediatric liver transplants were performed between November
      1989 and April 1998 using tacrolimus-based immunosuppression. Patients were
      followed until March 2002. Mean follow-up was 9.2+/-2.4 years. RESULTS: At 1
      year, 279 patients (85.5%) were alive. In the subsequent 12.5 years, 10 of the
      remaining children died (3.58%) at a mean interval of 3.68+/-1.69 years after
      transplant. The mean age at transplant was 5.62+/-6.3 years. Six patients had
      infections as a major contributor to mortality, including two patients with
      posttransplant lymphoproliferative disorder (PTLD) and one patient that died
      after retransplantation for hepatitis. Two patients had recurrent malignancy.
      Other deaths were attributable to chronic rejection, liver failure after being
      lost to follow-up, and complications of cystic fibrosis. CONCLUSIONS: Pediatric
      liver transplantation using tacrolimus-based immunosuppression has demonstrated
      excellent success, with 1- and 10-year survival rates of 85.5% and 82.9%,
      respectively. Late mortality after pediatric liver transplantation overall
      remains low, with a rate of 0.32% per year. The most common cause of death was
      infection (60%), including PTLD-related disease (20%). However, in the recent
      cohort of patients who underwent transplantation after September 1995, there were
      no fatal cases of Epstein-Barr virus or PTLD or late mortality thus far,
      suggesting a benefit from improved infectious disease surveillance using
      currently available modalities. Mortality from chronic rejection and
      noncompliance under tacrolimus has been exceedingly rare.

PMID- 12499889
TI  - Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive
      regimen in stable kidney transplant recipients: a randomized, controlled study.
AB  - BACKGROUND: Long-term maintenance immunosuppression with cyclosporine (CsA) is
      associated with chronic transplant nephropathy and adverse effects on blood
      pressure and lipid profile. Several nonrandomized studies suggest that CsA might
      safely be withdrawn from immunosuppressive regimens containing mycophenolate
      mofetil (MMF; CellCept). METHODS: A randomized, controlled study with 187
      patients enrolled from 21 centers was conducted to compare CsA withdrawal with
      ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug
      immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids.
      The primary endpoint was creatinine clearance at 6 months after complete
      withdrawal. RESULTS: In the intent-to-treat population, CsA withdrawal was
      associated with lower total cholesterol and low-density lipoprotein cholesterol (
      0.3 mmol/L, P=0.02; -0.4 mmol/L, P=0.015). There was a trend toward improved
      creatinine clearance (4.5 mL/min, P=0.16) and serum creatinine (-1 vs. +4
      micromol/L, P=0.34). In the per-protocol population, which excluded patients with
      acute rejections, the improvements in creatinine clearance and serum creatinine
      were statistically significant (7.5 mL/min, P=0.02; -11 vs. +4 micromol/L,
      P=0.0003). Reversible acute rejections, the majority of which were mild, occurred
      in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of
      each group, P=0.03), with no graft loss. CONCLUSION: Withdrawal of CsA from an
      MMF-containing triple-drug immunosuppressive regimen improves renal function and
      lipid profile at the cost of a modest increase in acute rejections, without graft
      loss.

PMID- 12499890
TI  - Initial experience with the modified extracorporeal liver-assist device for
      patients with fulminant hepatic failure: system modifications and clinical
      impact.
AB  - BACKGROUND: The need to find a safe, effective liver support system for patients
      with fulminant hepatic failure (FHF) continues to be unmet. A system using
      immortalized human hepatocytes was originally developed in the early 1990s. A
      modified version of the initial extracorporeal liver-assist device (ELAD) was
      recently placed into an initial clinical trial at the University of Chicago. The
      goal of this study was to determine the safety profile of the device at one
      center before broadening the study to other sites. METHODS: Patients who were
      diagnosed with FHF and admitted to the University of Chicago were eligible for
      the ELAD study. Informed consent was obtained, and patients received continuous
      ELAD therapy until and throughout transplantation. Data were prospectively
      collected and subsequently analyzed. RESULTS: Five patients were treated with the
      device. All patients successfully underwent transplantation. Four of the five
      patients survived to the 30-day endpoint of the study. There were no
      biomechanical problems identified. The patients' hemodynamic conditions did not
      deteriorate during treatment. The adult patients' clinical courses appeared to
      stabilize while connected to the ELAD (mean arterial pressure range 80-97, mean
      88.6; cerebral perfusion pressure range 62-88, mean 76.5). Patient 4 experienced
      remarkable improvement during ELAD therapy: elimination of phenylephrine,
      reduction of dopamine from 20 microg/min to 5 microg/min, and reduction of
      respiratory support from 100% O2, 10 cm positive end-expiratory pressure to 60%
      O2, and 5 cm H2O positive end-expiratory pressure. The device continued to be
      metabolically active throughout the study period as documented by oxygen use
      (mean O2 change from sampling port before cartridge to sampling port after
      cartridge for all patients treated = 55 mm Hg). CONCLUSIONS: The patients
      tolerated treatment with the ELAD well. There were no unanticipated safety
      issues. The cells in the cartridges were metabolically active. All patients
      successfully underwent transplantation. The results from this single-institution
      experience indicates that larger randomized multicenter trials should proceed.

PMID- 12499891
TI  - Low recurrence rate of hepatocellular carcinoma after liver transplantation:
      better patient selection or lower immunosuppression?
AB  - BACKGROUND: Liver transplantation is currently offered to a limited number of
      patients with hepatocellular carcinoma (HCC) because of strict criteria
      introduced in the past to avoid recurrence. Immunosuppression represents a risk
      factor for tumor growth; the schedules of the immunosuppressant drugs have been
      modified through the years, aiming to reduce their dosage to the effective
      minimum. METHODS: A series of 106 consecutive patients with HCC who underwent
      transplantation over a 15-year period at a single institution was retrospectively
      reviewed to ascertain whether tumor recurrence was influenced by the Milano
      criteria presently adopted in patient selection and whether the dosage of
      immunosuppressant agents administered was associated with tumor recurrence.
      Fifteen patients who died postoperatively and 9 with a follow-up of less than 1
      year were excluded; presence of the Milano criteria, tumor-node-metastasis
      staging, and the cumulative dosage of the single immunosuppressants given at
      different intervals in the first postoperative year were analyzed in the
      remaining 82 patients. The influence of these variables on overall and recurrence
      free survival was assessed statistically. RESULTS: The Milano criteria did not
      influence recurrence-free survival, which was instead associated with the
      cumulative dosage of cyclosporine administered in the first postoperative year
      (93% 5-year recurrence-free survival for patients given low dosage vs. 76% for
      those given high dosage; P=0.01); T3 and T4 tumors did worse than T1 and T2
      tumors. CONCLUSIONS: Current limits to transplantation for HCC might be
      reassessed in view of modified patient management; immunosuppression should be
      minimized in these patients.

PMID- 12499892
TI  - Objective and noninvasive metabolic characterization of donor hearts by
      phosphorous-31 magnetic resonance spectroscopy.
AB  - OBJECTIVE: The authors performed a multi-institutional, prospective, blind study
      on hearts from local donors to validate the feasibility and accuracy of the
      metabolic evaluation of human hearts by phosphorus-31 ( P) magnetic resonance
      spectroscopy (MRS) before transplantation. METHODS: Twenty-one hearts were
      separated into two groups according to a transplantation score (TS) on the basis
      of the current clinical and echocardiographic evaluation as follows: TS1 (n=7),
      grafts for United Network for Organ Sharing (UNOS) 1 patients only; and TS2
      (n=14), grafts suitable for UNOS 2 patients. All hearts were cold preserved with
      Celsior and underwent ex situ P MRS to measure ratios of various high-energy
      phosphate metabolites and the intracellular pH (pHi). RESULTS: The total duration
      of the MRS procedure was 32 min, thereby not unacceptably increasing the total
      ischemic time for the transplanted grafts. Phosphocreatine (PCr) and inorganic
      phosphate (Pi ) was significantly different between the two groups (0.95+/-0.29
      for TS1 and 2.05+/-0.74 for TS2). The difference in pHi was also significant
      (7.44+/-0.13 for TS1 and 7.64+/-0.19 for TS2). CONCLUSIONS: Determination of PCr
      Pi and pHi as markers of ischemic injury before transplantation can be considered
      as an objective and accurate criterion for the decision to accept or refuse heart
      grafts for transplantation.

PMID- 12499893
TI  - Toward further expansion of the organ pool for adult liver recipients: splitting
      the cadaveric liver into right and left lobes.
AB  - BACKGROUND: Current methods of living donor right lobe transplantation can be
      expanded for use in the cadaveric setting. The aim of this study is to discuss
      alternative methods for the management of large-for-size cadaveric livers and
      determine the feasibility of splitting these organs into left and right hemi
      livers using similar techniques to those used in the living donor setting.
      METHODS: The indication for an in situ right-left split procedure was an offer of
      a large liver for a small recipient with a recipient-donor ratio of greater than
      1.5. A total of three livers were split. Mean donor age was 33.3 (range, 22-40)
      years. Mean weight was 118 (range, 90-150) kg. All donors were without
      significant medical history and were hemodynamically stable, with normal liver
      function and short hospital stay. Mean duration of the procurement procedure was
      235 (range, 210-270) min. Mean cold ischemia time was 8.5 hr. Mean recipient
      weight was 58.3 kg, and mean donor to recipient weight ratio was 2.0 (1.6-2.6).
      United Network for Organ Sharing statuses at the time of transplantation were 1
      (n=1), 2A (n=1), and 2B (n=4). RESULTS: Immediate graft function was seen in five
      recipients. Delayed nonfunction was identified in one recipient of a left lobe,
      who did not undergo transplantation because of sepsis that resulted in death at
      30 days. A second mortality occurred in a left lobe recipient, from a fungal
      brain abscess at 90 days. Complications related to the split included bile leaks
      in two patients, one necessitating operative revision. CONCLUSIONS: Splitting of
      livers from appropriate brain-dead donors into right and left lobes is
      technically and logistically feasible. The large-for-size organ provides a more
      substantial amount of liver tissue to each of the adult recipients, which may
      result in a greater graft to recipient weight ratio than the current standard
      that is used in the living donor grafting. The importance of this variable will
      need to be studied, because it may positively impact on the ability of the
      reduced-size graft to withstand donor-related organ system stress and injury,
      which is associated with brain death and the inevitable longer period of cold
      preservation.

PMID- 12499894
TI  - Achievement of insulin independence in three consecutive type-1 diabetic patients
      via pancreatic islet transplantation using islets isolated at a remote islet
      isolation center.
AB  - BACKGROUND: As a result of advances in both immunosuppressive protocols and
      pancreatic islet isolation techniques, insulin independence has recently been
      achieved in several patients with type 1 diabetes mellitus via pancreatic islet
      transplantation (PIT). Although the dissemination of immunosuppressive protocols
      is quite easy, transferring the knowledge and expertise required to isolate a
      large number of quality human islets for transplantation is a far greater
      challenge. Therefore, in an attempt to centralize the critical islet processing
      needed for islet transplantation and to avoid the development of another islet
      processing center, we have established a collaborative islet transplant program
      between two geographically distant transplant centers. PATIENTS AND METHODS:
      Three consecutive patients with type 1 diabetes mellitus with a history of severe
      hypoglycemia and metabolic instability underwent PIT at the Methodist Hospital
      (TMH), Houston, Texas, using pancreatic islets. All pancreatic islets were
      isolated from pancreata procured in Houston and subsequently transported for
      isolation to the Human Islet Cell Processing Facility of the Diabetes Research
      Institute (DRI) at the University of Miami, Miami, Florida. Pancreatic islets
      were isolated at DRI after enzymatic ductal perfusion (Liberase-HI) by the
      automated method (Ricordi Chamber) using endotoxin-free and xenoprotein-free
      media. After purification, the islets were immediately transported back to TMH
      and transplanted via percutaneous transhepatic portal embolization.
      Immunosuppression consisted of sirolimus, tacrolimus, and daclizumab. RESULTS:
      After donor cross-clamp in Houston, donor pancreata arrived at DRI and the
      isolation process began within 6.5 hr in all cases (median, 5.4 hr; range, 4.8
      6.5 hr). At the completion of the isolation process, the islets were immediately
      transported back to TMH and transplanted. All three patients attained sustained
      insulin independence after transplantation of 395,567, 394,381, and 563,206
      pancreatic islet equivalents (IEQ), respectively. Despite insulin independence,
      the first two patients received less than 10,000 IEQ/kg; therefore, to increase
      their functional pancreatic islet reserve, they underwent a second islet
      transplant with 326,720 and 768,132 IEQ, respectively. Posttransplantation follow
      up for these three patients is 4, 3, and 0.5 months, respectively. The mean
      glycosylated hemoglobin values have been dramatically reduced in the first two
      patients. In addition, the mean amplitude of glycemic excursions have also been
      reduced in all three recipients (patient 1: before transplantation 197 mg/dL vs.
      after transplantation 61 mg/dL; patient 2: before transplantation 202 mg/dL vs.
      after transplantation 52 mg/dL; patient 3: before transplantation 245 mg/dL vs.
      after transplantation 58 mg/dL) after PIT. All pancreatic islet allografts
      demonstrated the ability to respond to an in vitro glucose stimulus at the DRI
      before shipment and at TMH after shipment and final processing with a median
      stimulation index of 2.1 and 2.2, respectively. None of the transplant recipients
      have had a hyper- or hypoglycemic episode since PIT and no complications have
      occurred. CONCLUSIONS: These early data demonstrate that (1) pancreatic islets
      remain viable after shipment to remote transplant sites; (2) pancreatic islet
      isolation techniques and experience can be concentrated at a small number of
      regional facilities that could supply islets to remote transplant centers; and
      (3) insulin independence via PIT can be achieved using a remote pancreatic islet
      isolation center.

PMID- 12499895
TI  - Remission of hepatitis C virus-associated cryoglobulinemic glomerulonephritis
      with interferon alfa-2b and ribavirin combination therapy after liver
      transplantation.

PMID- 12499896
TI  - Changes in tissue-oxidative stress markers in an experimental model of
      laparoscopic donor nephrectomy.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) is associated with prolonged
      warm ischemia, which could potentially increase oxidative stress in the graft.
      Because pneumoperitoneum (Pp) used to facilitate LDN impairs renal perfusion, it
      could augment the effects of warm ischemia. Our experimental, randomized,
      controlled study with blind outcome assessment is the first to address this
      possibility. METHODS: Wistar-Albino rats were randomized to 4 groups. Controls
      were subjected to a sham operation; the remainder were subjected to Pp with or
      without warm ischemia of differing durations. The kidneys were removed at the end
      of each experiment. The concentrations of malondialdehyde (MDA), protein
      carbonyl, and sulfhydryl groups and the activities of superoxide dismutase (SOD)
      and catalase were measured in renal samples as markers of oxidative stress. Renal
      samples were also evaluated histopathologically using light microscopy. RESULTS:
      Pp promoted oxidative stress in renal tissues, with an increase of MDA and
      protein carbonyls and a decrease in protein sulfhydryls and SOD activity. Warm
      ischemia exerted an additive effect on Pp-associated oxidative stress only when
      sustained for 10 minutes. These changes occurred in the absence of light
      microscopic evidence of overt tissue damage. CONCLUSION: In an experimental model
      resembling LDN, Pp and 10 minutes of warm ischemia emerged as additive factors
      with respect to causing increased oxidative stress in the kidney. Because these
      effects imply subtle injury not only in the harvested kidneys of live donors but
      also in the kidneys the donors retain, avoiding Pp and warm ischemia above 5
      minutes during LDN appears advisable.

PMID- 12499897
TI  - Targeted cloning of cytotoxic T cells specific for minor histocompatibility
      antigens restricted by HLA class I molecules of interest.
AB  - BACKGROUND: T cells specific for minor histocompatibility antigens (mHAgs) play a
      major role in both graft-versus-host disease and the graft-versus-tumor effect
      after HLA-identical bone marrow transplantation (BMT). However, characterization
      of individual T-cell responses to mHAgs is difficult and has generally involved
      extensive screening of T-cell clones isolated from bulk T-cell cultures generated
      from BMT recipients. In this report, we describe a new approach that permits both
      direct visualization of CD8 T-cell responses to mHAgs and cloning of T cells
      reacting with mHAgs presented by individual HLA alleles of interest. METHODS AND
      RESULTS: Panels of Epstein-Barr virus-transformed B-cell lines (B-LCL) expressing
      retrovirally transduced HLA cDNA were used as stimulator cells in an enzyme
      linked immunospot (ELISPOT) assay to identify CD8 T cells reacting with mHAgs in
      cultures generated from postBMT recipient peripheral blood. T cells specific for
      mHAgs presented by selected HLA alleles could then be captured and cloned using
      an interferon-gamma secretion assay and magnetic bead selection. A majority of T
      cell clones thus isolated exhibited cytolytic activity against the same HLA
      transfected B-cell lines used for the ELISPOT assay. CONCLUSION: The ELISPOT
      assay was useful for identification of the HLA alleles presenting mHAgs
      recognized by individual T-cell lines. This approach for isolating mHAgs-specific
      CD8 T-cell clones should assist in characterizing responses restricted by HLA
      alleles of interest, which are common in a certain ethnic group.

PMID- 12499898
TI  - Glucose-regulated insulin production in hepatocytes.
AB  - BACKGROUND: A gene-therapy-based treatment of type 1 diabetes mellitus requires
      the development of a surrogate beta cell that can synthesize and secrete
      functionally active insulin in response to physiologically relevant changes in
      ambient glucose levels. Failure to duplicate the storage-granule-based mechanism
      of insulin secretion of beta cells, however, has made it difficult to develop a
      surrogate beta cell. The authors' strategy for achieving glucose-dependent
      insulin secretion relies on glucose-responsive transcription of insulin mRNA and
      the constitutive secretory pathway of liver cells. METHODS: Insulin gene
      constructs containing three S14-based glucose-inducible regulatory elements, the
      liver-specific albumin promoter, and the human insulin cDNA modified for furin
      cleavage compatibility, were prepared and evaluated for biologic function in
      hepatocytes, in vitro, and in diabetic rats in vivo. RESULTS: The authors'
      insulin gene constructs induced insulin expression in hepatocytes. All detectable
      insulin produced by transduced hepatocytes in vitro was secreted, and the amount
      was dependent on the concentration of glucose and the duration of glucose
      stimulation. Analysis of in vivo functional efficacy of insulin gene therapy in
      streptozotocin-treated diabetic rats revealed the following: (1) fasting blood
      glucose levels were reduced to normal; (2) blood glucose levels of rats fed ad
      libitum were significantly reduced; and (3) peak blood glucose levels during oral
      glucose tolerance tests were significantly reduced. CONCLUSIONS: These studies
      demonstrate in vivo glucose-regulated insulin secretion from an autologous non
      beta cell leading to fasting euglycemia and an improved glucose tolerance,
      thereby supporting the feasibility of hepatocyte-based insulin gene-therapy for
      treatment of type 1 diabetes mellitus.

PMID- 12499899
TI  - Proteinuria in "normal" cadaver kidney donors.
AB  - BACKGROUND: More information is needed about cadaver organ donor pathophysiology.
      METHODS: We quantitated preprocurement, timed urine protein excretion in 23
      "normal" cadaver kidney donors, and correlated results with urine protein
      dipstick readings and multiple other parameters. We also attempted to measure
      microalbuminia in 10 subjects. RESULTS: Seventeen of 23 cadaver donors did not
      have detectable proteinuria (albuminuria) by urine dipstick testing but had
      1,704+/-2,900 mg (mean+/-SD) of quantitated daily urine protein, which did not
      correlate with creatinine clearance or urine volume. Donors with head trauma had
      numerically more quantitated proteinuria (3,000+/-5,160 vs. 970+/-670 mg/day,
      P=0.13). Microalbumin varied from 3 to 34% of the total urine protein
      concentration. CONCLUSIONS: Significant proteinuria as measured by quantitative
      collection techniques is often present in excellent cadaver kidney donors and is
      not detected by dipstick testing. It may be a marker of important terminal
      pathophysiologic events and deserves further study.

PMID- 12499900
TI  - Plasminogen activator inhibitor-1 polymorphism is associated with progressive
      renal dysfunction after acute rejection in renal transplant recipients.
AB  - BACKGROUND: Plasma level of plasminogen activator inhibitor (PAI)-1 is
      genetically determined by a polymorphism in the promoter region, involving two
      alleles, 4G and 5G. Plasma PAI-1 concentrations are higher in subjects homozygous
      for the 4G allele than other genotypes (5G/5G and 4G/5G). Such genetic variation
      in fibrinolytic system may affect the long-term renal transplant outcome.
      METHODS: We determined PAI-1 4G/5G-promoter genotype polymorphism among our renal
      transplant recipients between 1985 and 2001. Primary event was defined as
      doubling of baseline serum-creatinine level. RESULTS: Over a median period of 79
      months, 130 patients with 132 kidney grafts were assessed. Baseline clinical
      variables were comparable among three genotype groups. There was no association
      between primary event and PAI-1 genotype among the entire cohort. However, among
      subjects with prior acute rejection episodes, those homozygous for 4G had
      significantly higher risk of serum creatinine doubling than the other two
      genotypes (relative risk 2.45, 95% confidence interval 1.19-5.04). PAI-1 genotype
      does not predict primary events in patients without rejection (relative risk
      0.57, 95% confidence interval 0.07-4.17). CONCLUSIONS: PAI-1 4G/5G-promoter
      polymorphism modulates the risk of renal transplant outcomes after acute
      rejection(s). Recipients homozygous for PAI-1 4G allele have a higher risk of
      progressive renal damage after acute rejection episode(s). PAI-1 promoter
      polymorphisms are potentially important determinants of renal response to
      rejection.

PMID- 12499901
TI  - Variability of cyclosporine exposure and its relevance to chronic allograft
      nephropathy: a case-control study.
AB  - BACKGROUND: Population data indicate that cyclosporine (CsA)-based
      immunosuppression has had relatively little effect on late renal allograft loss.
      For individual patients, however, the degree and variability of CsA exposure may
      be of prognostic importance. This case-control study has examined the
      contribution of these and other factors to the development of chronic allograft
      nephropathy (CAN) in patients receiving follow-up care in our unit. METHODS: The
      electronic record was interrogated to identify adult, CsA-treated renal
      transplant recipients with CAN (group A) and CsA-treated controls with stable
      graft function for a minimum of 4 years posttransplantation and serum creatinine
      less than 200 micromol/L (group B). Age at transplantation, gender, years
      posttransplantation, donor source and age, kidney preservation time, human
      leukocyte antigen match, occurrence of delayed graft function, immunosuppressive
      regimen, weight-adjusted maintenance CsA dose, and coefficient of variation
      (CvarC0 ) of dose-adjusted CsA trough blood levels (C0/dose) were recorded
      (CvarC0 =[SD (C0/dose)/mean (C0/dose)]x100). Statistical analysis included binary
      logistic regression analysis. RESULTS: Three transplant recipients were excluded
      because of known noncompliance with immunosuppressive medication, leaving a study
      population of 102 patients. Recipient age (A<B, <0.001), CvarC0 (A>B, <0.01) and
      CsA dose (A>B, <0.02) were significantly different by univariate analysis. Only
      low recipient age ( P<0.001) and high CvarC0 ( P<0.02) were independent
      predictors of CAN in the regression model. CONCLUSION: Younger renal transplant
      recipients and those with highly variable CsA exposure are predisposed to
      developing CAN. Investigation of such patients may reveal correctable factors
      such as poor treatment compliance and lead to appropriate interventions.

PMID- 12499902
TI  - Hypereosinophilia as a presenting sign of acute graft-versus-host disease after
      allogeneic bone marrow transplantation.
AB  - The authors report two cases of hypereosinophilia as the major presenting sign of
      acute graft-versus-host disease (GVHD) after allogeneic bone marrow
      transplantation (BMT). Tissue biopsies of the skin, salivary gland, gut, and
      liver showed evidence of acute GVHD (aGVHD). In one case, further investigations
      have been performed. Elevated levels of interleukin (IL)-5 and soluble IL-2
      receptor were found in the blood, and skin biopsy specimens demonstrated high
      levels of IL-5 messenger ribonucleic acid (mRNA). In contrast, skin biopsy
      specimens from other patients with aGVHD but without eosinophilia were negative
      for IL-5 mRNA. The authors also demonstrated the presence of IL-4 and
      interferon(IFN)-gamma mRNA within the same skin biopsy specimen, suggesting that
      this case of aGVHD was mediated by both Th1 and Th2 cell type. These two patients
      were treated by glucocorticoids with resolution of the hypereosinophilia and the
      symptoms of GVHD. The authors briefly discuss the possible mechanisms of this
      hypereosinophilia with respect to aGVHD.

PMID- 12499903
TI  - H2O2-mediated oxidative stress versus cold ischemia-reperfusion: mitochondrial
      respiratory defects in cultured human endothelial cells.
AB  - Oxidative stress to vascular endothelium plays an important role in cold ischemia
      reperfusion (CIR) injury. We compared mitochondrial and plasma membrane integrity
      in human endothelial cells after 20-min exposure to 500 microM H2O or 8-hr cold
      ischemia and simulated reperfusion. In both groups, plasma membrane integrity was
      maintained but respiration was significantly decreased, as measured by high
      resolution respirometry. Uncoupling was more pronounced after H2O exposure
      compared with CIR. After H2O exposure, complex I respiration was significantly
      reduced, whereas CIR resulted additionally in a significant inhibition of complex
      II and IV respiration. Our results point to a partial overlap of the patterns of
      mitochondrial defects after H2O-mediated and CIR injury. In this respect, H2O
      exposure proved to be a useful model to study the mechanisms of CIR injury to
      human endothelial cells, whereas the full pattern of CIR injury could not be
      induced by a pulse of hydrogen peroxide exposure.

PMID- 12499904
TI  - Perfluorocarbon for organ preservation before transplantation.
AB  - Perfluorocarbons (PFC) are hydrocarbons in which all or most of the hydrogen
      atoms have been replaced with fluorine. PFC have a very high capacity for
      dissolving oxygen (O2 ), and a negligible oxygen-binding constant allows them to
      release O2 more effectively than hemoglobin into the surrounding tissue. As a
      result of this unique property, PFC-based solutions have been examined as oxygen
      carriers. PFC was first used for organ preservation as a component of the two
      layer method (TLM) (University of Wisconsin [UW] solution-perfluorochemical plus
      oxygen) of pancreas preservation. Pancreata preserved in the TLM are oxygenated
      through the PFC and substrates are supplied by the UW solution. This allows
      pancreata stored in the TLM to generate adenosine triphosphate during storage and
      prolong the preservation period. In the canine model, TLM has been shown to
      repair and resuscitate warm ischemically injured pancreata during preservation,
      improve pancreas graft survival after transplantation, and improve islet yields
      after isolation. Current clinical trials using the TLM of pancreas preservation
      before whole-pancreas transplantation and islet isolation show promising results.
      The TLM has also been shown to be beneficial for preserving other difficult
      organs, such as heart and small bowel.

PMID- 12499905
TI  - Preservation of the human pancreas before islet isolation using a two-layer (UW
      solution-perfluorochemical) cold storage method.

PMID- 12499906
TI  - Use of oxygenated perfluorocarbon toward making every pancreas count.
AB  - The past few years have seen significant advancement in the clinical relevance of
      intraportal islet cell transplantation for treatment of type 1 diabetes mellitus.
      The implementation of novel protocols, such as the one developed by the group of
      Shapiro and collaborators in Edmonton, has revitalized the enthusiasm for
      cellular transplantation as a treatment for diabetes by improving the success
      rates and long-term function of islet grafts. Improved results in clinical islet
      transplantation reported by the groups in Edmonton, Miami, and Minneapolis have
      re-proposed the much simpler outpatient cell transplant procedure as an
      alternative to the more risky and technically challenging whole-organ pancreas
      transplantation.

PMID- 12499907
TI  - Impact of two-layer pancreas preservation on islet isolation and transplantation.

PMID- 12499908
TI  - Selected Food and Drug Administration review issues for regulation of allogeneic
      islets of langerhans as somatic cell therapy.
AB  - The Food and Drug Administration has seen a significant increase in
      investigational new drug (IND) applications for the use of allogeneic islets of
      Langerhans to treat type 1 diabetes mellitus. The current regulatory framework
      for clinical use of allogeneic islets of Langerhans is described. In addition,
      expectations and considerations for information to be included in the
      manufacturing, preclinical, and clinical sections of an IND for allogeneic islets
      of Langerhans to treat type 1 diabetes mellitus are discussed.

PMID- 12499909
TI  - Lipase supplementation therapy: standards, alternatives, and perspectives.
AB  - Treatment of steatorrhea by lipase supplementation therapy has become more
      successful in the last decade due to better understanding of the physiology and
      pathophysiology of the digestive process. Porcine lipase has been the therapeutic
      standard for several decades and will continue to be the treatment of choice in
      pancreatic exocrine insufficiency. Modern therapeutic concepts recommend
      administration of 25,000-40,000 units of porcine lipase per meal using pH
      sensitive pancreatin microspheres. In case of treatment failure, the dose should
      be increased, compliance should be checked, and other reasons for malabsorption
      should be excluded. Still, in most patients, lipid digestion cannot be completely
      normalized by current standard therapy, and future developments are needed for
      optimizing treatment. In this article, pathophysiologic characteristics of
      pancreatic exocrine insufficiency, prerequisites for use of alternative lipase
      sources as well as currently available lipases of nonporcine origin, and new
      developments are discussed. Current literature suggests that bovine lipase
      products present a theoretical alternative but play no major role in the western
      world. Fungal lipase has inferior properties compared with conventional products.
      Bacterial lipase products show promising potential and offer future therapeutic
      alternatives. Moreover, human pancreatic lipase gene transfer and application of
      bioengineered human gastric lipase appear on the horizon.

PMID- 12499910
TI  - Potentially fatal bleeding in acute pancreatitis: pathophysiology, prevention,
      and treatment.
AB  - INTRODUCTION: Massive bleeding may complicate the course of either acute or
      chronic pancreatitis. Although the latter is more frequently involved when
      bleeding occurs in the acute form, a poorer prognosis is to be expected. Abscess,
      severe inflammation, regional necrosis, and pseudocysts may cause major vessel
      erosion, with or without pseudoaneurysm formation, whose eventual rupture may
      result in massive bleeding into the gastrointestinal tract, retroperitoneum, and
      peritoneal cavity. AIMS: To define the most important pathophysiologic mechanisms
      and factors that might contribute to a better understanding, better prevention,
      and more efficient treatment of severe hemorrhage complicating acute necrotizing
      pancreatitis. Awareness of high-risk conditions occurring during the natural
      evolution of the disease (from extensive local severe enzymatic damage to late
      septic sequelae), avoidance of a too early and too aggressive approach to sterile
      pancreatic necrosis, and providing prompt and effective treatment of local septic
      complications, when they occur, are crucial steps for bleeding prevention.
      METHODOLOGY: Forty-four cases of severe bleeding following acute pancreatitis
      that were reported during the last decade since 1992 (including the six cases
      reported here) are reviewed, analyzed, and summarized. RESULTS: The overall
      mortality rate was 34.1%. Splenic artery, portal vein, spleen, and unspecified
      peripancreatic vessels were the most commonly involved sources of bleeding, with
      associated mortality rates of 33.3%, 50.0%, 30%, and 28.5%, respectively. Massive
      hemorrhage was more frequently associated with severe necrosis, with a mortality
      rate of 37.9%. CONCLUSION: The increased use of diagnostic and interventional
      radiology, in association with prompt surgical treatment, appears to be the way
      to improve survival rates in cases of arterial bleeding. Venous bleeding due to
      lesion of major peripancreatic veins or diffuse bleeding represents a therapeutic
      challenge, and treatment of these conditions should be tailored to the individual
      case, as no general rule can be suggested. In extreme cases, open packing or
      salvage emergency pancreatectomy may represent the only chances for survival.

PMID- 12499911
TI  - The pH modulator chloroquine blocks trypsinogen activation peptide generation in
      cerulein-induced pancreatitis.
AB  - INTRODUCTION AND AIMS: We examined the effects of a weak base, chloroquine, on
      the trypsinogen processing in cerulein-induced pancreatitis. METHODOLOGY:
      Immunofluorescence studies were performed using newly generated affinity-purified
      antibodies to the trypsinogen activation peptide (TAP). RESULTS: The present
      study showed that chloroquine pretreatment blocked intracellular TAP generation
      in cerulein-induced pancreatitis. CONCLUSION: These results indicate that
      intracellular trypsinogen activation, which plays an important role in acute
      pancreatitis, requires a low-pH compartment, as well as serine protease activity.

PMID- 12499912
TI  - The early increase in intestinal permeability and systemic endotoxin exposure in
      patients with severe acute pancreatitis is not associated with systemic bacterial
      translocation: molecular investigation of microbial DNA in the blood.
AB  - INTRODUCTION: Sepsis is the main cause of late mortality in patients with severe
      acute pancreatitis and is largely attributed to secondary infection of pancreatic
      necrosis with gram-negative enteric organisms. This is commonly preceded by a
      significant increase in intestinal colonization with such microbes and with early
      increases in intestinal permeability, thus suggesting a mechanism of bacterial
      translocation. Whilst cultures of blood specimens from these patients often
      remain sterile, it is conceivable that bacteria might translocate in small
      volumes with detrimental effects but elude detection by standard microbial
      culture techniques. AIMS: To investigate the incidence and frequency with which
      bacterial DNA may exist in the systemic circulation of patients with acute
      pancreatitis and to relate that to disease severity, changes in intestinal
      permeability, and systemic endotoxin exposure. METHODOLOGY: Blood samples were
      obtained at admission and on days 3 and 7 from 26 patients with acute
      pancreatitis (seven with severe cases) and from 10 healthy controls for DNA
      extraction and standard microbial cultures. Polymerase chain reaction techniques
      were used to amplify a gene region (16S ribosomal RNA) found in all bacteria.
      Levels of serum endotoxin and antibodies to endotoxin core (EndoCAb) were
      measured at admission, and intestinal permeability to the macromolecule
      polyethylene glycol 3350 was determined within 72 hours of the onset of symptoms.
      RESULTS: Blood cultures yielded and enterococci for one patient with a severe
      attack and coagulase-negative staphylococci for another patient with a mild
      attack. No bacterial DNA was found in any of the samples. Endotoxemia was
      detected in 20 patients (five with severe cases), and levels of serum IgM EndoCAb
      were depleted in patients with severe attacks but remained relatively unchanged
      during mild attacks (p = 0.033). Intestinal permeability was significantly
      increased in patients with severe attacks of acute pancreatitis but remained
      unchanged during mild attacks (p < 0.05). CONCLUSIONS: Whilst severe attacks of
      acute pancreatitis are associated with early derangement in gut barrier function
      and systemic endotoxin translocation, there is no molecular evidence for
      associated bacterial "translocation."

PMID- 12499913
TI  - Expression of antioxidant enzymes in diseases of the human pancreas: another link
      between chronic pancreatitis and pancreatic cancer.
AB  - INTRODUCTION: Chronic pancreatitis is a significant risk factor for pancreatic
      cancer and is associated with the generation of reactive oxygen species. Cells
      contain a large number of antioxidants to prevent or repair the damage caused by
      reactive oxygen species. There are three major types of primary intracellular
      antioxidant enzymes in mammalian cells: superoxide dismutase (SOD), catalase, and
      peroxidase, of which glutathione peroxidase is the most prominent. AIM: To
      determine the level of antioxidant enzymes in human pancreas from normal, chronic
      pancreatitis, and pancreatic cancer specimens. METHODOLOGY: Immunohistochemical
      analysis for manganese SOD, copper/zinc SOD, catalase, and glutathione peroxidase
      expression using the avidin-biotin-peroxidase complex method was performed on
      pancreatic specimens previously fixed in formalin and embedded in paraffin. A
      quantitative digital imaging methodology was used to examine antioxidant staining
      in the pancreatic tissue. Cytoplasmic regions of ductal and acinar cells were
      identified and digitized. Mean gray-level pixel values were then obtained for
      each of these regions. RESULTS: Cytoplasmic values of manganese SOD, catalase,
      and glutathione peroxidase were decreased in pancreatic cells from chronic
      pancreatitis specimens when compared with normal pancreas. In pancreatic
      carcinoma specimens, mean cytoplasmic gray-level values of all antioxidant
      enzymes were decreased when compared with normal pancreas. CONCLUSION: There
      appears to be a gradual decrease in antioxidant enzyme expression in pancreatic
      cells from normal pancreas to chronic pancreatitis to pancreatic cancer.

PMID- 12499914
TI  - Clinicopathologic analysis of pancreatic adenocarcinoma in African Americans and
      Caucasians.
AB  - INTRODUCTION: African Americans have a higher incidence of pancreatic
      adenocarcinoma than do Caucasians for unknown reasons. Whether other
      clinicopathologic differences exist between these two groups is not known. This
      study was undertaken to compare the clinical, pathologic, and biologic findings
      for a group of patients with a histologic diagnosis of pancreatic ductal
      adenocarcinoma of the usual type in a single institution. METHODOLOGY: We studied
      410 patients (166 African Americans and 244 Caucasians) with a histologic
      diagnosis of pancreatic ductal adenocarcinoma of the usual type and analyzed (a)
      the clinicopathologic characteristics of the tumors, (b) the immunohistochemical
      expression of biomarkers implicated in pancreatic carcinogenesis (Fas, Fas
      ligand, HER2, p21/waf-1, p27, and p53), and (c) the presence and types of K-
      mutations at codon 12 as determined by polymerase chain reaction-mediated
      amplification. All elements of data were not available for all patients. RESULTS:
      African Americans had significantly higher rates of K-ras mutations to valine
      than did Caucasians (58% versus 22%, respectively; p = 0.015) and were less
      likely to have received chemotherapy (45% versus 70%, respectively; p = 0.001) or
      radiation therapy (34% versus 57%, respectively; p = 0.003). African Americans
      also had more frequent positive surgical margins than did Caucasians (56% versus
      25%, respectively; p = 0.001), although mean tumor size was similar between the
      two groups (African Americans, 3.4 cm; Caucasians, 3.5 cm). Other
      clinicopathologic variables were similar between the two groups, including median
      survival (African Americans, 8.5 months; Caucasians, 10.1 months), 5-year
      survival (African Americans, 3%; Caucasians, 6%), and stage at presentation.
      Differences in biomarker immunoreactivity included less frequent Fas expression
      (4% versus 24%, respectively; p = 0.048) and a trend toward more frequent strong
      HER2 expression (39% versus 18%, respectively p = 0.11) in African Americans than
      in Caucasians. CONCLUSION: Although African American and Caucasian patients had
      similar survival rates associated with usual type pancreatic ductal
      adenocarcinoma, there were differences in management and expression of biologic
      markers between these two groups. African Americans were significantly less
      likely to receive radiation therapy or chemotherapy than were Caucasians, which
      may assume more importance as treatment improves. At the molecular level, African
      Americans had more frequent K- mutations to valine than did Caucasians.

PMID- 12499915
TI  - The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in
      pancreatic cancer cells independent of COX-2.
AB  - INTRODUCTION: Selective cyclooxygenase-2 (COX-2) inhibition reduces the growth of
      many cancer cell lines, and this effect may be mediated through induction of
      apoptosis. This study was designed to investigate the effects of the COX-2
      inhibitor nimesulide on the growth of human pancreatic cancer cells. METHODOLOGY:
      Reverse transcriptase-polymerase chain reaction analysis, northern blotting, and
      immunoblotting were used to demonstrate COX-2 mRNA and protein in two pancreatic
      cancer cell lines: BxPC-3 and MIA PaCa-2. The effect of nimesulide on cell growth
      was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      assay and cell count. Apoptosis was determined by FACS analysis, DNA laddering,
      and assessment of the floating cell/attached cell ratio. Caspase-3 activation was
      evaluated by measuring caspase-3 cellular activity and by determining the effects
      of two caspase inhibitors on cell viability. RESULTS: COX-2 mRNA was detected in
      both cell lines. Immunoblotting confirmed COX-2 protein expression in only the
      BxPC-3 cell line. Nimesulide decreased cell viability and inhibited cell growth
      in both cell lines. Incubation with 100 micromol/L nimesulide increased the
      fraction of apoptotic cells and the floating cell/attached cell ratio in both
      cell lines. DNA laddering was observed after incubation with nimesulide for 96
      hours. There was no increase in caspase-3 activity within 96 hours. CONCLUSION:
      The selective COX-2 inhibitor nimesulide is antimitogenic in pancreatic cancer
      cells, which is independent of COX-2 expression. This effect in part is mediated
      by the induction of apoptosis.

PMID- 12499916
TI  - Tumor-suppressing pathways in cystic pancreatic tumors.
AB  - INTRODUCTION AND AIMS: Serous and mucinous cystic pancreatic tumors have
      different clinical behavior. We evaluated whether they also have genotypic
      differences by analyses of the tumor suppressor genes, p16INK4a, p53, and DPC4.
      METHODOLOGY: Seven serous cystadenomas (SCA) and seven malignant mucinous
      cystadenocarcinomas (MCC) were analyzed for alterations in the tumor suppressor
      genes p16INK4a, p53, and DPC4 by single-strand conformational variant analysis,
      direct sequencing, and immunohistochemical analysis. Methylation-specific
      polymerase chain reaction analysis was performed to identify p16INK4a promoter
      hypermethylation. Clinical data were compared with genetic data. RESULTS: None of
      the seven patients with SCAs but five of the seven patients with MCCs died of the
      tumor after a median follow-up of 44.5 months (range, 4-169 months). All seven
      MCCs had alterations in at least one tumor suppressor gene compared with none of
      the seven SCAs. Of the seven MCCs, three had inactivating p16INK4a promoter
      hypermethylation, five had p53 alterations, and three had DPC4 mutations.
      CONCLUSIONS: The tumor suppressor genes p16INK4a, p53, and appear to play an
      important role in the tumorigenesis of MCCs but not SCAs. These molecular data
      underscore the clinical and histologic differences of serous and mucinous cystic
      pancreatic tumors.

PMID- 12499917
TI  - Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1
      in pancreatic cancer.
AB  - INTRODUCTION: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is
      one of the membrane molecules expressed on human cancer cells and is presumed to
      play a protective role for tumor cells against immune surveillance by inhibition
      of clonal expansion and induction of cell death in immunocytes. AIMS: To address
      whether RCAS1 is expressed in pancreatic cancer and whether serologic diagnostic
      evaluation is useful compared with that of carbohydrate antigen 19-9 (CA19-9) and
      soluble Fas ligand. METHODOLOGY: Immunohistochemical expression of RCAS1 was
      examined by staining with a 22-1-1 monoclonal antibody, and serum RCAS1
      concentrations were determined by an enzyme-linked immunosorbent assay in 20
      cases of ductal adenocarcinoma of the pancreas and other pancreatic diseases.
      RESULTS: Immunohistochemically, RCAS1 detection occurred in 100% (20/20) of
      ductal adenocarcinoma of the pancreas cases, 100% (6/6) of intraductal papillary
      mucinous adenoma of the pancreas cases, and 40% (2/5) of chronic pancreatitis
      cases. RCAS1 was found in the cytoplasm of cancer cells and ductal cells. Serum
      RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were
      significantly higher than those in patients with chronic pancreatitis (p <
      0.0001), acute pancreatitis (p < 0.005), and autoimmune pancreatitis (p < 0.001).
      RCAS1 concentrations in patients with intraductal papillary-mucinous adenoma of
      the pancreas were also significantly higher than those in patients with chronic
      pancreatitis (p < 0.05) and autoimmune pancreatitis (p < 0.05). Positive serum
      RCAS1 samples (concentration, > or = 10 U/mL) were found most often in cases of
      pancreatic neoplasm (80% [16/20], ductal adenocarcinoma of the pancreas; and 60%
      [3/5], intraductal papillary-mucinous adenoma of the pancreas). By contrast, in
      cases of pancreatic inflammatory diseases, raised concentrations occurred in 9.4%
      (3/32) of chronic pancreatitis cases, none (0/6) of acute pancreatitis cases, and
      none (0/8) of autoimmune pancreatitis cases. The sensitivity of CA19-9 for ductal
      adenocarcinoma of the pancreas was 75% and the specificity was 73.1% compared
      with chronic pancreatitis. On the other hand, the sensitivity of RCAS1 for ductal
      adenocarcinoma of the pancreas was 80% and the specificity was 96.2% compared
      with chronic pancreatitis. The specificity of RCAS1 for chronic pancreatitis was
      higher than that of CA19-9. Serum soluble Fas ligand concentrations were not
      considerably different among these patients. CONCLUSIONS: RCAS1 was highly
      expressed in ductal adenocarcinoma of the pancreas, and serum RCAS1
      concentrations in patients with ductal adenocarcinoma of the pancreas were
      significantly higher than those in patients with other inflammatory pancreatic
      diseases. Our results indicate that serum RCAS1 concentrations could be a new
      marker in screening procedures for pancreatic cancer.

PMID- 12499918
TI  - Hypoxia-inducible factor 1 regulates vascular endothelial growth factor
      expression in human pancreatic cancer.
AB  - INTRODUCTION: The microenvironment of low oxygen that is present in human
      pancreatic cancer in vivo may actively influence tumor growth as well as
      neovascularization. AIMS: To determine whether hypoxia-inducible factor 1 (HIF-1)
      is specifically activated by hypoxia in vitro in pancreatic cancer cells and
      correlated these findings with tumor specimens. METHODOLOGY: Hypoxic regulation
      of vascular endothelial growth factor (VEGF) was studied by northern blot
      analysis and enzyme-linked immunosorbent assay. Electrophoretic mobility shift
      assays and western blot analysis were used to demonstrate hypoxic activation of
      HIF-1. The relationship between HIF-1 and VEGF in human pancreatic cancer
      specimens was studied by immunohistochemical analysis, northern blot analysis,
      and in situ hybridization. RESULTS: Studies in vivo of human pancreatic cancer
      tissue showed co-localization of VEGF mRNA, which is produced in ductal cancer
      cells, and HIF-1alpha protein, which was detectable in cell nuclei of the same
      cells. HIF-1alpha mRNA expression was dramatically upregulated (approximately 13
      fold) in these specimens as well. In vitro, all pancreatic cancer cell lines
      increased VEGF production when exposed to low oxygen levels, by highly specific
      activation of HIF-1 DNA binding activity to the VEGF promoter. Cancer cell lines
      with high constitutive levels of HIF-1alpha protein were found to produce higher
      basal levels of VEGF. CONCLUSION: We conclude that HIF-1 is the regulatory link
      between tumor hypoxia and VEGF production in pancreatic cancer, thus establishing
      a biochemical pathway between tumor hypoxia and neoangiogenesis in this highly
      aggressive neoplasm.

PMID- 12499919
TI  - C-JUN and CPP32 (CASPASE 3) in human pancreatic cancer: relation to cell
      proliferation and death.
AB  - INTRODUCTION: There is strong evidence that tumor growth is not only a result of
      uncontrolled cell proliferation but also of decreased apoptosis. AIMS: To
      ascertain the expression of c-Jun in specimens of pancreatic duct cancer and to
      evaluate its correlation with CPP32, apoptotic index, and proliferation index
      (MIB-1). METHODS: Tissue samples were collected from 23 patients with pancreatic
      duct cancer who had not received chemotherapy nor radiation therapy before
      surgery. In these specimens we determined the expression of c-Jun protein, CPP32,
      and MIB-1 by immunohistochemical method. Apoptosis was studied by the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling method. RESULTS: CPP32/caspase3 was expressed in 83% and c-Jun in 87% of
      primary lesions. Three of 23 samples were completely negative for c-Jun, and 4 of
      23 were negative for CPP32. Three of 4 specimens negative for CPP32 showed low or
      negative c-Jun. A significant correlation was found between CPP32/caspase3 and c
      Jun (r = 0.51; p < 0.01) and between c-Jun and MIB-1 (r = 0.57; p < 0.004). No
      correlation was found between CPP32, c-Jun, MIB-1, and apoptotic index.
      CONCLUSIONS: The positive correlation between the expression of c-Jun and CPP32
      and the absence of both in the same specimens suggest that a common factor or
      common factors induce the expression of both genes. Pancreatic cancer tissue with
      an increased percentage of proliferating tumor cells showed also a strong
      expression of c-Jun, which supports the hypothesis that this oncogene may be
      involved in the growth of pancreatic cancer. We hypothesize that under different
      extracellular stimuli both death and proliferation are activated in neoplastic
      cell, probably under the control of transcription factor AP-1.

PMID- 12499920
TI  - Analysis of gene expression and insulin secretion by monolayer-forming adult
      porcine pancreatic endocrine cells.
AB  - INTRODUCTION: We recently established a method of isolation and primary monolayer
      culture of porcine pancreatic endocrine cells that involves the use of
      nicotinamide. AIM: To obtain genetic information on cultured porcine endocrine
      cells and to examine cell function in relation to insulin secretion during long
      term culture. METHODOLOGY: Gene expression of insulin and several transcription
      factors, including PDX-1, Beta2/NeuroD, Pax6, and Nkx6.1, was assessed by reverse
      transcription-polymerase chain reaction analysis, and the insulin protein level
      was estimated by immunohistochemistry and enzyme assay during a 12-week period.
      RESULTS: During the culture period, insulin accumulation in the medium at 5 weeks
      had decreased by almost half the level of accumulation in the first week. In
      contrast to the alteration of secretory function, insulin gene expression was
      maintained for at least 12 weeks, and regulatory transcription factors were
      expressed at the same levels until 9 weeks. These observations suggest that gene
      expression is not involved in the cause of decreased baseline insulin secretion.
      Moreover, although the insulin response to high glucose and potassium loading was
      maintained, the magnitude of the responses to both stimuli was attenuated in the
      late period of culture. Insulin secretion tended to decrease in our culture
      system, and the secretory response to pharmacological stimulation was attenuated
      despite maintenance of messenger RNA expression of insulin and other islet
      specific genes for at least 9 weeks in vitro. CONCLUSION: These findings indicate
      that cell integrity is maintained and that the alteration in insulin secretion
      must be explained by another mechanism.

PMID- 12499921
TI  - Differentiation of neuroendocrine tumors from other pancreatic lesions by echo
      enhanced power Doppler sonography and somatostatin receptor scintigraphy.
AB  - BACKGROUND AND AIMS: Echo-enhanced power Doppler sonography is a noninvasive
      procedure that has been increasingly used for the differential diagnosis of
      pancreatic tumors. However, to our knowledge, the diagnostic accuracy of this
      procedure in comparison with somatostatin receptor scintigraphy for the
      differentiation of neuroendocrine lesions from other pancreatic tumors has never
      been investigated in a prospective, controlled study. SUBJECTS AND METHODS: One
      hundred thirty-seven patients were included in the study; the patients were
      selected from 190 consecutive patients (mean age, 59.8 years; range, 16-85 years)
      who presented to our department from January 1998 through June 2001 with
      suspicion of a pancreatic tumor. An experienced examiner who was unaware of the
      patients' clinical diagnoses performed sonography. Twenty-nine patients with
      sonographically and/or clinically suspected neuroendocrine tumors were
      investigated additionally by somatostatin receptor scintigraphy. The exact
      diagnosis was based upon histologic evidence from biopsy examination (surgical
      and transabdominal fine-needle biopsy) or a follow-up of at least 18 months.
      RESULTS: The sensitivity of echo-enhanced power Doppler sonography for diagnosing
      a neuroendocrine pancreatic tumor was 94%, and its specificity was 96%. The
      corresponding values for somatostatin receptor scintigraphy were 54% and 81%,
      respectively. CONCLUSIONS: Echo-enhanced power Doppler sonography has high
      sensitivity and high specificity for the differentiation of neuroendocrine
      lesions from other pancreatic tumors. However, histologic evidence is the
      standard of reference for the differential diagnosis of pancreatic tumors.

PMID- 12499922
TI  - Stretch activation of Ca2+ transients in pancreatic beta cells by mobilization of
      intracellular stores.
AB  - INTRODUCTION: Nonadrenergic, noncholinergic neurons have been proposed to
      synchronize pulsatile insulin release from the islets in the pancreas by
      triggering transient increases of the cytoplasmic Ca2+ concentration ([Ca2+]i) in
      beta-cells via an inositol trisphoshate-dependent mechanism. AIMS: To test
      whether pancreatic beta-cells respond to stretch activation with similar types of
      transients and whether these Ca signals propagate to other beta-cells in the
      presence and absence of cell contacts. METHODOLOGY: Single cells and small
      aggregates were prepared from beta-cell-rich islets from mice. After 2-5 days of
      culture, [Ca2+]i was measured with digital imaging and the indicator fura-2
      during superfusion with a medium containing 20 mmol/L glucose and 50 micromol/L
      methoxyverapamil. Membrane stretch was induced by osmotic swelling or focal touch
      stimulation. RESULTS: Lowering the medium osmolarity with 100-102 mOSM/L by
      removal of sucrose or by dilution resulted in a 2-3-fold increase in the number
      of transients during an initial 5-minute period. Sucrose omission was stimulatory
      also after isosmolar replacement with readily penetrating urea. The intracellular
      Ca2+-ATPase inhibitor thapsigargin suppressed both the spontaneously occurring
      transients and those initiated by volume expansion. Touch stimuli induced [Ca2+]i
      transients, which rapidly propagated to cells within the same aggregate or
      lacking contact. CONCLUSION: The observations support the idea that beta-cells
      both receive and regenerate extracellular signals triggering [Ca2+]i transients.
      Touch stimulation is a useful tool for investigating the propagation of [Ca2+]i
      signals between pancreatic beta-cells lacking physical contact.

PMID- 12499923
TI  - Effect of cholecystokinin1 receptor antagonist loxiglumide (CR1505) on basal
      pancreatic exocrine secretion in conscious rats.
AB  - INTRODUCTION AND AIM: To examine the involvement of cholecystokinin (CCK) in the
      basal pancreatic exocrine, we investigated the effect of loxiglumide (CR1505), a
      CCK1 receptor antagonist, on basal pancreatic exocrine secretion in conscious
      rats. METHODOLOGY: After the basal collection of pancreatic juice for 1 hour,
      loxiglumide (10 mg/kg/h) or saline was infused via the femoral vein continuously
      for 2 hours. RESULTS: Loxiglumide significantly suppressed the basal pancreatic
      protein and amylase outputs. However, loxiglumide did not alter the basal
      pancreatic juice volume. CONCLUSIONS: These results demonstrate that loxiglumide
      suppresses basal pancreatic exocrine secretion in normal rats. They also suggest
      that CCK is involved in basal pancreatic exocrine in conscious rats and that
      loxiglumide may be useful as a therapeutic agent for pancreatitis, even during
      fasting, by attenuating the basal pancreatic exocrine burden on the pancreas.

PMID- 12499924
TI  - Case of chronic pancreatitis involving an autoimmune mechanism that extended to
      retroperitoneal fibrosis.

PMID- 12499925
TI  - Nonocclusive visceral ischemia associated with severe acute pancreatitis.

PMID- 12499926
TI  - Giant lipoma of the pancreas: case report and review of lipomatous lesions of the
      pancreas.

PMID- 12499927
TI  - Catastrophic intraabdominal bleeding due to rupture of pancreaticoduodenal artery
      aneurysm: successful transcatheter arterial embolization.

PMID- 12499928
TI  - A 43-year-old man was admitted to the hospital with the diagnosis of acute
      pancreatitis of 4 days' duration.

PMID- 12499929
TI  - Isolation, culture, and functional characteristics of diabetic islets
      [corrected].

PMID- 12499930
TI  - Effect of hepatocyte growth factor (HGF) on adult islet function in vitro
      [corrected].

PMID- 12499931
TI  - 2nd international symposium: Frontiers in pancreatic research-from basics to
      clinic and exocrine glands, Japan-Korea.

PMID- 12499932
TI  - Effects of moderate hypothermia on proinflammatory cytokine production in a rat
      model of caerulein-induced pancreatitis.
AB  - INTRODUCTION: Proinflammatory cytokines act as mediators of the local and
      systemic manifestations of acute pancreatitis (AP). AIMS: To investigate whether
      moderate hypothermia (MH) (32 degrees C) can reduce the severity of AP by
      inhibiting cytokine production in a rat model of caerulein-induced pancreatitis.
      METHODOLOGY: Rats were divided into three groups: control rats (Group I), AP rats
      treated with normothermia (38 degrees C) (Group II), and AP rats treated with MH
      (Group III). AP was induced by intramuscular injection of caerulein and
      intraperitoneal infusion of lipopolysaccharide. MH was induced 4 hours after the
      first caerulein injection. Serum interleukin (IL)-1beta, tumor necrosis factor
      (TNF)-alpha, IL-6, amylase, and lipase levels were determined 8 hours after the
      first injection. The pancreas and lung were examined histologically. RESULTS: MH
      in comparison with normothermia significantly reduced serum levels of IL-1beta,
      TNF-alpha, IL-6, amylase, and lipase. Histologically, the MH group showed less
      vacuolization of the acinar cells and cellular infiltration into the interacinar
      areas of the pancreas than were shown in the normothermia group, but these
      effects were not evident in the lung. CONCLUSION: Our results suggest that MH may
      be clinically applicable for reducing the severity of AP.

PMID- 12499933
TI  - Characterization of gap junctional intercellular communication in immortalized
      human pancreatic ductal epithelial cells with stem cell characteristics.
AB  - INTRODUCTION: Gap junctional intercellular communication has been implicated in
      the homeostatic regulation of cell growth, differentiation, and apoptosis. Cancer
      cells, which have been viewed as "partially blocked stem cells," and which lack
      the ability for growth control, terminal differentiation, and apoptosis, also
      lack functional gap junctional communication. AIMS AND METHODOLOGY: A clone of a
      human pancreatic ductal epithelial cell line, H6c7, derived after immortalization
      with human papilloma virus, was used to examine gap junctional intercellular
      communication and the ability to differentiate under different growth conditions.
      RESULTS: The cells showed characteristic epithelial morphology on standard tissue
      culture dishes. When placed on Matrigel they showed phenotypical changes with
      extensive ductal organization and budding structures. In growth medium containing
      hormones and growth factors, these cells were gap junctional intercellular
      communication (GJIC)-incompetent. In the presence of c-AMP elevating agents,
      isobutylmethylxanthine, and forskolin, in basal medium that did not contain the
      hormones and growth factors, the cells became GJIC-competent and expressed
      connexin43 gap junction protein within 48 hours after treatment. RT-PCR analyses
      of the cells under different growth conditions showed that the cells expressed,
      and genes when cultured in the basal medium with c-AMP elevating agents. They
      also expressed the gene that did not change with c-AMP treatment. H6c7 cells also
      have the capacity to turn on an ectopic insulin promoter reporter gene.
      CONCLUSION: Our data suggest that the immortalized H6c7 cells retain stem-like
      characteristics and have the potential to differentiate into duct-like structures
      and perhaps insulin-producing cells.

PMID- 12499934
TI  - Results of medial open reduction of the hip in infants with developmental
      dislocation of the hip.
AB  - Thirty-two patients who had medial open reduction of 40 hips were reviewed at an
      average of 10.3 years follow-up (range 2.5-18.6 y). Center-edge angles and
      acetabular indices were measured on preoperative, postoperative, and final
      radiographs. The presence of AVN was noted. The final radiograph was assigned a
      Severin grade. One hip re-dislocated. Eight (20%) have required subsequent pelvic
      osteotomies. AVN developed in 11 hips (27.5%). Of the 11, five were classified as
      type I, defined as temporary irregular ossification of the femoral head.
      Bilateral dislocations and age older than 1 year at surgery correlated with
      greater likelihood of AVN ( < 0.05), whereas absence of the ossific nucleus did
      not. Thirty hips were classified as Severin 1 or 2, six were rated Severin 3, and
      three were Severin 4. Nineteen patients completed gait analysis. Normal motion
      was documented in 12 of 14 unilateral patients. Significant hip flexor and
      extensor isokinetic weakness was seen. In conclusion, medial open reduction
      yielded satisfactory results in 75% of hips. Although iliopsoas weakness is
      common, gait is usually normal.

PMID- 12499935
TI  - Hip dislocation in patients with spinal muscular atrophy.
AB  - The propensity for hip dislocation in patients with spinal muscular atrophy (SMA)
      is well documented, but the appropriate treatment and even the long-term outcome
      of these hips in this patient population have not been well defined. The purpose
      of this study was to determine by long-term follow-up the natural history of
      dislocated hips in a cohort of SMA patients from a single institution. Pain and
      functional difficulties (positioning, skin and perineal care) were assessed and
      radiographs were reviewed in a total of 41 patients with a mean of 18 years of
      follow-up. Seventeen of 82 hips (21%) were dislocated in 14 patients and 20 hips
      were subluxed. Only two patients had any hip pain at follow-up, one had
      difficulty with seating, and no patients had difficulty with perineal care. Given
      the small number of patients with symptoms with dislocated hips, observation
      rather than surgical intervention seems warranted in SMA patients with hip
      dislocation.

PMID- 12499936
TI  - Treatment of the collapsed femoral head by containment in Legg-Calve-Perthes
      disease.
AB  - One hundred ninety-seven patients with unilateral Legg-Calve-Perthes disease
      (LCPD) were followed-up to skeletal maturity. According to the lateral pillar
      classification, 142 hips were classified as group B and 55 hips as group C.
      Radiographs were evaluated for percent of collapse of the femoral head,
      Waldenstrom stage of disease at diagnosis, Mose sphericity, hinge abduction,
      lateral acetabular shape, and limb-length discrepancy. The hips were treated
      either by bedrest and traction in abduction (76), Petrie cast (21), abduction
      brace (74), or by pelvic or femoral osteotomy (26). One hundred twenty-five hips
      had less than a 2-mm difference in Mose sphericity at followup. According to the
      classification of Stulberg et al., 89 hips (45%) were class I, 57 (29%) were
      class II, 35 (18%) were class III, 12 (6%) were class IV, and 4 (2%) were class
      V. Analyses revealed statistically significant differences between group B versus
      group C with regard to the classifications of Stulberg et al. and Mose, lateral
      acetabular shape, age at onset, and limb-length discrepancy. There was no
      significant statistical difference with regard to the types of treatment.
      Containment treatment of a deformed femoral head from LCPD improves the
      sphericity of the hip and gives 63% satisfactory results according to the Mose
      classification and 74% satisfactory results according to the Stulberg et al.
      classification.

PMID- 12499937
TI  - Coxa vara with proximal femoral growth arrest in patients who had neonatal
      extracorporeal membrane oxygenation.
AB  - This is a retrospective review of four patients in whom a pattern of coxa vara
      with proximal femoral growth arrest and metaphyseal irregularities developed.
      These patients were all treated with neonatal extracorporeal membrane oxygenation
      and presented with a progressive gait disturbance and pain, leg-length
      discrepancy, and limited abduction. Imaging revealed coxa vara with proximal
      femoral growth arrest. Two patients (three hips) underwent proximal femoral
      valgus osteotomy, one patient underwent fixation of a femoral neck fracture with
      subsequent greater trochanter transfer, and one patient is being observed. This
      case series suggests an association between neonatal extracorporeal membrane
      oxygenation and this unusual pattern of coxa vara with proximal femoral growth
      arrest.

PMID- 12499938
TI  - In situ pinning of hip for stable slipped capital femoral epiphysis on a
      radiolucent operating table.
AB  - Patients with stable slipped capital femoral epiphysis (SCFE) usually can
      ambulate at the time of diagnosis. Satisfactory results have been reported after
      percutaneous in situ pinning using a fracture table. The authors describe a
      technique to determine the skin-pin entry point for percutaneous pinning of the
      hip on a regular radiolucent operating table. The pin entry point determined by
      this modified method was reliable in 15 SCFEs in 13 patients. Pinning on a
      regular radiolucent table was much easier, without the need to transfer obese
      patients to a fracture table. It was also useful when a bilateral pinning
      procedure was performed using single draping. Obtaining modified frog-leg lateral
      radiographs in patients with a stable SCFE was not associated with avascular
      necrosis or chondrolysis.

PMID- 12499939
TI  - Fibular hemimelia: a new classification system.
AB  - A new classification system for fibular hemimelia is proposed based on the
      authors' experience with 32 patients with 33 involved limbs representing a
      spectrum of involvement. The data demonstrate the broad and unpredictable
      relationships among the fibula, ankle, and foot in this disorder. The
      classification system, based on fibular and ankle morphology, hindfoot coalition,
      and foot ray deficits, is designed to improve communication about the condition.
      Because of the variability and unpredictability of the multiple relationships,
      limb salvage criteria should also include the nature of the foot and ankle and
      not merely depend on the length discrepancy or the presence or absence of the
      fibula.

PMID- 12499940
TI  - Effects of irradiation on the appositional and longitudinal growth of the tibia
      and fibula of the rat with and without radioprotectant.
AB  - The effect of therapeutic levels of irradiation on appositional bone growth was
      compared with its effect on longitudinal growth in the skeletally immature rat
      model. The widths and lengths of the tibiae and fibulae of young rats were
      studied at 2, 4, 6, and 12 weeks after exposure to 17.5 Gy x-irradiation to the
      knee region of the right leg, with and without the aminothiol radioprotectant
      amifostine 20 minutes before radiation. Irradiation retarded growth in the width
      of the tibia to a greater extent (19%-27%) than longitudinal growth (9%-21%). The
      appositional growth discrepancy decreased over time, whereas the length
      discrepancy increased. The proximal fibula, in contrast, undergoes a normal
      decrease in width over time, and irradiation retarded this contraction by 14%.
      Appositional growth does not appear to be spared from the damaging effects of
      irradiation, but a catch-up phenomenon is observed that is not seen in
      longitudinal growth. Amifostine reduced the radiation-induced loss in tibial
      width by 40% to 50% and in length by 12% to 30%.

PMID- 12499941
TI  - Use of distraction osteogenesis techniques in skeletal dysplasias.
AB  - The authors report the results of 63 operations performed on patients with
      skeletal dysplasias using the techniques of distraction osteogenesis. There were
      a total of 26 patients (16 males, 10 females) with a mean age of 12.5 years. The
      group had 13 different skeletal dysplasias. In 55 of 63 (87%) of the procedures,
      the objectives of surgery were achieved. The authors review their results with
      reference to the type of fixator used and the underlying diagnosis. Circular
      frames were associated with improved results. Spondylometaphyseal dysplasia and
      Jeune syndrome were the only dysplasias treated that were associated with
      significant complications.

PMID- 12499942
TI  - Effect of low-intensity ultrasound stimulation on consolidation of the regenerate
      zone in a rat model of distraction osteogenesis.
AB  - This study was performed to explore the tissue-level changes in mineralization
      caused by low-intensity ultrasound stimulation after distraction osteogenesis.
      Unilateral femoral lengthenings (7 mm) were performed on 34 male Sprague-Dawley
      rats. Half of the animals received daily ultrasound stimulation for 5 weeks; the
      remaining animals received sham treatments. Healing was assessed with serial
      radiographs, quantitative micro-computed tomography, and biomechanical testing.
      Twenty-one animals were evaluated at the conclusion of the study (9 experimental,
      12 control). Radiographically, healing of the ultrasound-treated bones preceded
      that of the sham-treated bones by approximately 1 week. Bone volume fraction and
      trabecular bone pattern factor were significantly higher in the ultrasound
      treated animals, but there were no significant differences in bone mineral
      content or bone mineral density. The ultrasound-treated femurs were 20% stiffer
      and 33% stronger than the control femurs, but the differences were not
      statistically significant. These findings suggest that pulsed, low-intensity
      ultrasound matures the regenerate by altering the microarchitecture of the newly
      formed bone.

PMID- 12499943
TI  - Need for concomitant proximal fibular epiphysiodesis when performing a proximal
      tibial epiphysiodesis.
AB  - The purpose of this study was to determine: 1) if proximal tibial epiphysiodesis
      (PTE) results in fibular overgrowth if performed without a concomitant proximal
      fibular epiphysiodesis (PFE); 2) if fibular overgrowth is prevented by
      concomitant PFE; and 3) the complications associated with PFE. There were 44
      patients in the study, 33 who underwent PTE alone (group 1) and 11 who underwent
      PTE with concomitant PFE (group 2). Fibular overgrowth was measured at the knee
      and ankle. Proximal fibular overgrowth was significantly greater in group 1 (6.8
      mm) than in group 2 (3.1 mm, = 0.02) or in the control group (1.2 mm, < 0.05)
      over a similar period of time. At the ankle, fibular growth was not significantly
      different between groups. There were no surgical complications related to PFE.
      PFE appears safe and should be considered if there is predisposing fibular
      overgrowth or several years of remaining growth.

PMID- 12499945
TI  - Effect on balance and gait secondary to removal of the second toe for digital
      reconstruction: 5-year follow-up.
AB  - Foot anatomy and lower limb function were analyzed in 11 children (aged 6.5-12.5
      y) 5 years after removal of one or two second toes for digital reconstruction. In
      addition to physical examination and x-rays, postural balance and three
      dimensional measurements of gait were analyzed. Among the 15 operated feet, five
      had bridle scars, three had claw deformities of the third toe, five had pain in
      the first intermetatarsal space, and seven had overt or early-stage hallux valgus
      (including five after unilateral toe removal). Hallux valgus deformation was also
      observed in three nonoperated feet. Maintenance of balance and rate of
      displacement of the center of pressure when standing on one foot with eyes closed
      were significantly altered for operated limbs compared with nonoperated limbs.
      Gait was rapid because of increased step cadence. Foot progression angle and
      ankle and knee joint sagittal kinematics during walking were normal. Although
      children appeared to not be affected in their daily life by the removal of the
      second toe(s), related foot anatomic and functional modifications require further
      follow-up.

PMID- 12499944
TI  - Valgus deformity after fibular resection in children.
AB  - The authors present a retrospective study of 23 patients in their growing period
      who underwent resection of more than 2 cm of the fibula. Long-term effects in the
      ankle and tibia were analyzed. The patients were radiologically studied using the
      contralateral side as control. Representative radiologic findings were distal
      migration of the fibula head in 75% (but without clinical relevance), thickening
      of the external tibial cortex in 20%, talar tilt in 45%, proximal migration of
      the lateral malleolus in 55%, and diaphyseal valgus of the tibia in 20% of the
      cases. Incomplete regeneration of fibula was observed in 58% of the cases. Two
      patients suffered a spiral diaphyseal fracture and another a slow physeal
      fracture of the distal tibia. In this study, many radiologic changes were
      observed after fibula resection. The authors suggest using reconstruction methods
      after fibula resection when it is possible.

PMID- 12499946
TI  - Opening wedge osteotomy of the medial cuneiform before age 4 years in the
      treatment of forefoot adduction.
AB  - Thirty-seven feet in 25 children (12 girls, 13 boys) treated surgically with
      medial cuneiform opening wedge osteotomy to correct forefoot adduction were
      assessed. Thirteen patients had unilateral deformity. Primary diagnoses were
      congenital clubfoot (33 feet), congenital forefoot adduction (3 feet), and
      skewfoot (1 foot). All children underwent operation before age 4 years. The age
      at operation ranged from 21 to 47 months (mean 35). In 18 feet, allografts were
      used. In 5 feet, autograft was used. In 14 feet, ceramic material was inserted as
      opening wedge. Follow-up ranged from 3 to 8 years (mean 4). In four feet, the
      ossification center of the medial cuneiform was invisible. The correction of the
      deformity was assessed clinically and radiographically. The first ray angle and
      talo-first metatarsal angle were evaluated on anteroposterior radiographs, the
      latter was evaluated on lateral radiographs, also. In 26 feet, normal position of
      the forefoot was achieved. In five feet, overgrowth of the medial cuneiform in
      comparison with the normal side was observed. Forefoot adduction persisted in six
      feet. The ossification center was often divided into two parts by bone graft, and
      subsequent independent growth of both parts was observed. This technique is safe
      and useful for correction of forefoot adduction in young children. It can be
      performed even in cartilaginous bone. The osteotomy causes overgrowth of the
      medial cuneiform and the medial ray.

PMID- 12499947
TI  - Transcuneiform and opening wedge medial cuneiform osteotomy with closing wedge
      cuboid osteotomy in relapsed clubfoot.
AB  - Ten patients (13 feet) aged 4 to 11 years with idiopathic clubfeet underwent bony
      correction for resistant supination and adduction deformities. A closing wedge
      cuboid osteotomy and medial cuneiform opening wedge and transcuneiform osteotomy
      were performed in all cases. The average improvement in anteroposterior talo
      first metatarsal angle of 22 degrees, calcaneo-fifth metatarsal angle of 13
      degrees, and lateral calcaneo-first metatarsal of 9 degrees confirmed the
      clinically satisfactory correction in all feet. However, one foot required repeat
      surgery 2 years after the index procedure.

PMID- 12499948
TI  - Combined midfoot osteotomy for severe forefoot adductus.
AB  - A one-stage procedure combining a closing wedge osteotomy of the cuboid with an
      opening wedge of the medial cuneiform was used for the treatment of severe
      forefoot adductus. Results were reviewed in 33 patients (50 feet) followed-up for
      at least 2 years postoperatively. Clinical and radiographic improvement in
      forefoot position was achieved in 90% of cases. The mean calcaneo-second
      metatarsal angle improved from 37 degrees preoperatively to 18 degrees at final
      follow-up. The mean talo-first metatarsal angle improved from 15 degrees
      preoperatively to 3 degrees at final follow-up. The medial to lateral column
      ratio demonstrated 33% improvement after surgical treatment. Two feet were
      unimproved because of graft migration. Patients younger than age 5 years without
      a well-defined medial cuneiform ossific nucleus had a high rate of medial graft
      extrusion with loss of correction. This procedure should be reserved for patients
      aged 5 years or older. Ten patients followed-up for more than 6 years had no
      deterioration in results. This procedure provides effective, safe, predictable,
      and lasting correction of forefoot adductus.

PMID- 12499949
TI  - Implications of subtalar joint anatomic variation in calcaneal lengthening
      osteotomy.
AB  - The purpose of this study was to identify the percentage of individuals with
      distinct anterior and middle calcaneal facets. Calcaneal lengthening osteotomy,
      as popularized by Mosca, is extra-articular, with its site being the interval
      between the anterior and middle calcaneal facets. For individuals without a
      distinct anterior and middle facet, the subtalar joint must be violated to
      perform this operation. The authors studied 1,056 calcanei in 528 human cadavers
      from the Hamann-Todd Osteology Collection at the Cleveland Museum of Natural
      History. Findings were categorized using the Bunning and Barnett classification
      of subtalar facet configuration. Type A was found in 389 calcanei (37%), type B
      in 480 calcanei (46%), and type C in only two calcanei. Transitional type was
      found in 122 calcanei (12%). There was no anterior facet in 61 calcanei (6%).
      Asymmetry was found in 51 cadavers (10%). Most calcaneal lengthening osteotomies
      will occur intra-articularly, which may affect clinical results.

PMID- 12499950
TI  - Pulsed color-flow Doppler analysis of arterial deficiency in idiopathic clubfoot.
AB  - This prospective study used pulsed color-flow Doppler sonography to determine
      differences in the presence and direction of flow through the dorsalis pedis,
      posterior tibial, and peroneal arteries in a group of children with clubfoot and
      a comparison group of controls. There was a statistically significant difference
      in the prevalence of deficient (absent or retrograde flow) dorsalis pedis
      arteries in children with clubfoot (45%) compared with controls (8%). This
      indicates that there is an association between some clubfeet and deficiency of
      the dorsalis pedis artery. There was a trend toward difference in the prevalence
      of deficiency of the dorsalis pedis artery in the clubfeet that required surgery
      (54%) compared with those that did not (20%), suggesting that dorsalis pedis
      artery deficiency may be more prevalent among clubfeet with greater deformity.

PMID- 12499951
TI  - Dyggve-Melchior-Clausen syndrome: report of seven patients with the Smith-McCort
      variant and review of the literature.
AB  - Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder
      affecting skeletal development. The patients have a striking "barrel-shape"
      chest, shortened trunk, and various distal deformities, including genu valgum or
      varum, and minimal decrease in joint mobility. The most notable radiographic
      findings are a lacy iliac crest apophysis, hip dysplasia, double vertebral hump,
      and odontoid hypoplasia with atlanto-axial instability. Patients may require
      orthopedic femoral osteotomy, total hip arthroplasty, early meniscectomy,
      realignment osteotomy, or posterior cervical spine fusion. Patients with the
      Smith McCort variant have similar orthopaedic manifestations but are not mentally
      retarded. The diagnosis may be confirmed histologically, but no biochemical or
      developmental defect has been defined as yet. The authors report seven affected
      members of two families from Guam and describe their orthopaedic treatment. The
      authors review the historical reports, clinical findings, and diagnostic
      radiographic features in DMC syndrome.

PMID- 12499952
TI  - Costello syndrome: orthopaedic manifestations and functional health.
AB  - Sixteen individuals with Costello syndrome underwent a complete history, physical
      examination, and medical record review. Medical history and record review were
      performed for two additional children with Costello syndrome. The POSNA
      Functional Health Outcome Questionnaire Baseline Assessment was completed by the
      parents of all 18 children. All the children were below the fifth percentile for
      height and all had ligamentous laxity. All children demonstrated delayed walking
      and none was able to run. Orthopaedic problems included tight heel cords,
      congenital vertical talus, planovalgus feet, hip subluxation, kyphosis,
      scoliosis, radial head subluxation, elbow flexion deformity, reduced shoulder
      range of motion, and limitation of overhead activity. Foot problems were most
      frequently encountered. Two children had no orthopaedic symptoms. All children
      with Costello syndrome had poor scores on the POSNA Functional Health Outcome
      Questionnaire. Orthopaedic problems are a significant part of Costello syndrome,
      and affected individuals should be evaluated and followed-up regularly by an
      orthopaedic surgeon.

PMID- 12499953
TI  - Hemiatrophy.
AB  - The authors present a series of seven patients who have a diagnosis fitting that
      of combined ipsilateral facial and somatic hemiatrophy. Diagnostic features
      include facial, tongue, and ear asymmetry and associated decreases in length and
      size of the ipsilateral limbs. The symptomatic problems related to leg length
      discrepancy can be addressed in the usual fashion, and this condition does not
      appear to progress to large leg length discrepancies. The cosmetic side of this
      disorder is often concerning: it is the most reliable identification of the
      existence of this condition and is present from birth. Facial hemiatrophy is mild
      and does not appear to be progressive. The hemiatrophies probably have a
      multifactorial pathogenesis that most likely has at its basis a genetic cause.

PMID- 12499954
TI  - Role of magnetic resonance imaging and clinical criteria in predicting successful
      nonoperative treatment of osteochondritis dissecans in children.
AB  - Magnetic resonance imaging (MRI) offers promise as a noninvasive method to
      determine the potential of an osteochondritis dissecans (OCD) lesion to heal
      without surgical intervention. The purpose of this study was to compare the value
      of MRI, plain radiographs, and clinical findings in predicting the success of
      nonoperative treatment of juvenile OCD lesions. Twenty-seven lesions in 24
      patients (mean age 12.2 y) with OCD of the distal femur diagnosed based on MRI
      were identified. A radiologist or orthopaedist, blinded to the clinical status of
      the patients, correlated the MRIs with patient outcome. MRIs were assessed for
      lesion size, location, and four criteria evaluating signal intensity changes and
      articular surface defects to determine lesion stability. Older, more skeletally
      mature patients with at least one sign of instability on MRI were most likely to
      have nonoperative treatment fail. Nonoperative treatment failed most often in
      patients with large lesions in weightbearing areas, as seen on lateral
      radiographs. However, location based on anteroposterior radiographs was not
      statistically significant for predicting treatment outcome. Although no single
      factor was uniformly predictive of successful nonoperative treatment, younger,
      skeletally immature patients with no MRI criteria of instability were most
      amenable to nonoperative treatment.

PMID- 12499955
TI  - Changing glenoid version after open reduction of shoulders in children with
      obstetric brachial plexus palsy.
AB  - Twenty-three patients who had obstetric brachial plexus palsy and shoulder
      subluxation or dislocation that required open reduction and tendon lengthening
      were entered into a prospective study to evaluate glenoid version after surgery.
      All the patients had a preoperative computerized axial tomograph and
      postoperative computed tomography scan of both shoulders at approximately yearly
      intervals to assess the degree of congruity of the glenohumeral joint and glenoid
      version. Surgery was performed between 1988 and 1997. There were 11 girls and 12
      boys. The mean age was 2 years 5 months (range 8 months-6 years 7 months). The
      left shoulder was affected in 12 patients and the right shoulder was affected in
      11 patients. At mean follow-up of 3 years 7 months, the mean glenoid retroversion
      for the dislocated shoulder progressively decreased. The difference in glenoid
      version between the dislocated and the normal side decreased. The angle of
      glenoid retroversion in the affected shoulders decreased by a mean of 31% after
      open reduction, and the retroversion continued to improve at 9% per year.

PMID- 12499956
TI  - Lyme arthritis presenting as acute septic arthritis in children.
AB  - There is considerable overlap in the initial clinical and laboratory
      presentations of acute septic arthritis and Lyme arthritis. The authors present a
      consecutive case series of 10 children with acute arthritis consistent with
      septic arthritis who ultimately were diagnosed with Lyme disease. Fifty percent
      presented with a fever of 38 degrees C or higher. The peripheral white blood cell
      count and differential were not elevated, but the erythrocyte sedimentation rate
      and the C-reactive protein were significantly elevated. The joint fluid cell
      count was elevated, with 91% neutrophils. Seven patients in this series underwent
      emergent joint irrigation and debridement for presumed septic arthritis. The
      authors suggest that in regions where Lyme disease is endemic, children who
      present with presumed septic arthritis should also be evaluated for Lyme disease.
      The authors also present a protocol for evaluation and management of these
      diagnostically challenging cases.

PMID- 12499957
TI  - Multiple-level thoracolumbar burst fractures in teenaged patients.
AB  - The purpose of this study was to examine the characteristics of multiple-level
      burst fractures in teenaged patients. Five teenaged patients were identified with
      this injury pattern. The mean age at injury was 17.6 years. All five patients
      underwent a posterior fusion and an attempted decompression through
      ligamentotaxis. One of the five went on to have an anterior decompression. Four
      of the five patients had spinal instrumentation. Neurologic deficit was present
      in four patients. The proximal fracture was most often responsible for the
      neurologic deficit when present. The average length of follow-up was 4.5 years.
      There was no significant neurologic recovery after hospital discharge. Three of
      the five patients had minimal or no back pain at latest follow-up. The authors
      conclude that multiple burst fractures should be treated individually based on
      their clinical and radiographic characteristics.

PMID- 12499958
TI  - Langerhans cell histiocytosis of bone in children and adolescents.
AB  - The purpose of this paper was to analyze the orthopaedic aspects of Langerhans
      cell histiocytosis and to assess the outcome after treatment. Fifty-six patients
      with Langerhans cell histiocytosis involving the bone were retrospectively
      studied. Three groups were identified with regard to the type of bone
      involvement. Group I patients (n = 26) had a solitary bone lesion, with no
      systemic involvement. No treatment was given in 22 patients and curettage was
      done in 4 patients. At last follow-up, complete or partial healing was observed
      in 25 patients. Group II patients (n = 13) had multiple bone lesions, with no
      systemic involvement. Clinical and radiographic pictures as well as the outcome
      after treatment were similar to those in group I. Group III patients (n = 17) had
      bone and systemic involvement. Chemotherapy was used in all group III patients,
      with adjuvant radiotherapy in seven patients. Recurrence or new lesions were
      observed in 11 patients. Complications of treatment were observed in 14 patients.
      Lesions in group I and II patients had a considerable potential for spontaneous
      healing. Group III patients had the worst prognosis. Current chemotherapy
      protocols have a high morbidity and produce a variable response.

PMID- 12499959
TI  - Molecular and genetic approaches to musculoskeletal diseases.

PMID- 12499960
TI  - Should major surgery be the only intervention analyzed when determining the
      efficacy or cost-effectiveness of a hip-screening program?

PMID- 12499962
TI  - Interaction between active motion and exogenous transforming growth factor Beta
      during tibial fracture repair.
AB  - OBJECTIVE: Evaluate the effects of axial motion and transforming growth factor
      beta (TGF-beta) on callus formation and fracture healing.DESIGN Prospective
      experimental design with a 39-day postfracture recovery. SETTING: Unrestricted
      cage activity with weight bearing as tolerated. ANIMALS: Twenty-two skeletally
      mature, female New Zealand White rabbits. INTERVENTIONS: Displaced, closed tibial
      fractures were reduced and stabilized in external fixators on the fourth day
      following fracture. Half of the fixators were locked for the duration of healing.
      The other fixators were locked for one week, then unlocked for the remaining four
      weeks. Half of the fractures in each fixator group received two injections of
      recombinant human TGF-beta1 (rhTGF-beta1). One injection was administered at the
      time of reduction, and the second was given 48 hours later. MAIN OUTCOME
      MEASUREMENTS: Interfragmentary axial motion was measured during floor activity.
      Biomechanical properties were measured during a torsion test to failure. Callus
      area and the distribution of tissues within the callus were determined by
      computer-aided histomorphometry. RESULTS: The administration of TGF-beta1 did not
      alter callus size, mechanical properties, or the distribution of tissues in the
      callus of fractures that were stabilized in locked external fixators. Recoverable
      axial motion fixation increased callus size, quantity of mineralized bone
      bridging the fracture, and maximum torque relative to locked fixation. The
      injection of TGF-beta1 negated the beneficial effects of axial motion by
      promoting the formation of a peripheral callus bridged by fibrous tissue rather
      than mineralized trabecular bone. CONCLUSIONS: Injection of rhTGF-beta1 during
      the first postfracture week does not provide a biologic boost that improves
      fracture healing. Injection of TGF-beta1 may be detrimental to healing under
      conditions when fracture motion is present. The results suggest that there is a
      tendency for exposure to TGF-beta1 to inhibit the normal development of
      peripheral callus in response to axial interfragmentary motion.

PMID- 12499963
TI  - Controlled induction of a pseudarthrosis: a study using a rodent model.
AB  - OBJECTIVES: This study aimed to test the hypothesis that under standardized
      mechanical and biologic conditions, the process of indirect bone repair in a
      rodent species could be manipulated to form a reproducible, atrophic, fibrous
      pseudarthrosis. DESIGN: The model used comprised a mid-diaphyseal, transverse
      osteotomy in the rat femur, stabilized via a precision miniature external
      fixator, a constant axial fixation stiffness being defined by a specific frame
      geometry. MAIN OUTCOME MEASUREMENTS: The repair process for both 0.5-mm and 3.0
      mm gap osteotomies was characterized using radiography, dual-energy x-ray
      absorptiometry, histologic assessment of standardized longitudinal sections, and
      postmortem mechanical testing. RESULTS: Healing of the defect was highly
      reproducible, bone union being attained at around 5 weeks postoperatively with a
      0.5-mm gap. Increasing the gap width to 3.0 mm resulted consistently in a
      pseudarthrosis. CONCLUSION: These two reproducible patterns of repair can now be
      used to elucidate the underlying molecular mechanisms controlling the extent and
      progression of connective tissue differentiation in indirect bone repair without
      the additional variable of a nonstandardized mechanical environment.

PMID- 12499964
TI  - Triangular osteosynthesis and iliosacral screw fixation for unstable sacral
      fractures: a cadaveric and biomechanical evaluation under cyclic loads.
AB  - OBJECTIVE: To conduct a biomechanical comparison of a new triangular
      osteosynthesis and the standard iliosacral screw osteosynthesis for unstable
      transforaminal sacral fractures in the immediate postoperative situation as well
      as in the early postoperative weight-bearing period. DESIGN: Twelve preserved
      human cadaveric lumbopelvic specimens were cyclicly tested in a single-limb
      stance model. A transforaminal sacral fracture combined with ipsilateral superior
      and inferior pubic rami fractures were created and stabilized. Loads simulating
      muscle forces and body weight were applied. Fracture site displacement in three
      dimensions was evaluated using an electromagnetic motion sensor system.
      INTERVENTION: Specimens were randomly assigned to either an iliosacral and
      superior pubic ramus screw fixation or to a triangular osteosynthesis consisting
      of lumbopelvic stabilization (between L5 pedicle and posterior ilium) combined
      with iliosacral and superior pubic ramus screw fixation. MAIN OUTCOME MEASURES:
      Peak loaded displacement at the fracture site was measured for assessment of
      initial stability. Macroscopic fracture behavior through 10,000 cycles of
      loading, simulating the early postoperative weight-bearing period, was classified
      into type 1 with minimal motion at the fracture site, type 2 with complete
      displacement of the inferior pubic ramus, or type 3 with catastrophic failure.
      RESULTS: The triangular osteosynthesis had a statistically significantly smaller
      displacement under initial peak loads (mean +/- standard deviation [SD], 0.163 +/
      0.073 cm) and therefore greater initial stability than specimens with the
      standard iliosacral screw fixation (mean +/- SD, 0.611 +/- 0.453 cm) ( = 0.0104),
      independent of specimen age or sex. All specimens with the triangular
      osteosynthesis demonstrated type 1 fracture behavior, whereas iliosacral screw
      fixation resulted in one type 1, two type 2, and three type 3 fracture behaviors
      before or at 10,000 cycles of loading. CONCLUSION: Triangular osteosynthesis for
      unstable transforaminal sacral fractures provides significantly greater stability
      than iliosacral screw fixation under in vitro cyclic loading conditions. In vitro
      cyclic loading, as a limited simulation of early stages of patient mobilization
      in the postoperative period, allows for a time-dependent evaluation of any
      fracture fixation system.

PMID- 12499965
TI  - Midline sagittal sacral fractures in anterior-posterior compression pelvic ring
      injuries.
AB  - OBJECTIVE: To evaluate the outcome of an uncommon variant of the anterior
      posterior compression pelvic injury, in which the posterior ring injury is a
      midline sagittal sacral fracture extending into the spinal canal. DESIGN:
      Prospective, consecutive series. SETTING Two regional trauma centers. PATIENTS: A
      consecutive series of 10 patients with rotationally displaced, vertically stable
      anterior-posterior compression pelvic ring fractures (OTA type 61-B1) in which
      the posterior ring injury is a midline sagittally oriented sacral fracture
      involving the spinal canal (Denis zone III). This injury pattern comprised 0.6%
      of pelvic fractures and 1.4% of sacral fractures treated at these two
      institutions during a 10-year period. INTERVENTION: Patients were treated
      according to the same principles used in more commonly seen types of anterior
      posterior compression pelvic ring injuries. Nine patients were treated with
      reduction and anterior pelvic stabilization at an average of 5 days after injury,
      8 of whom were treated with open reduction and internal fixation and 1 with
      external fixation. No posterior pelvic fixation was used. One patient with
      nondisplaced bilateral pubic ramus fractures was treated nonoperatively.
      Immediate weight bearing was allowed as tolerated. MAIN OUTCOME MEASUREMENTS:
      Prospectively collected clinical follow-up data emphasized a detailed neurologic
      examination, whereas radiographic evaluation involved anteroposterior, inlet, and
      outlet plain radiographic views of the pelvis. RESULTS: An anatomical or near
      anatomical reduction of the pelvis was achieved and maintained in all patients.
      Fractures healed at an average of 10 weeks. At an average follow-up of 31 months
      (range 20-46 months), there were no objective neurologic deficits that could be
      attributed to sacral root injury and no significant residual pain or gait
      disturbance related to the pelvic fracture. Loss of bowel or bladder function,
      loss of perianal sensation or sphincter tone, and lumbosacral radicular pain or
      sensorimotor deficit were specifically absent in all patients. Three patients,
      however, complained of sexual dysfunction at final follow-up. None of these
      patients had clinical evidence of sacral root/plexus injury secondary to the
      fracture. One additional patient, who sustained a urethral tear, required a
      chronic suprapubic catheter because of stricture. Six patients, one of whom had
      needed repair of a retroperitoneal bladder tear, had no urogenital sequelae.
      DISCUSSION AND CONCLUSION: Patients who sustain sagittally oriented midline
      fractures of the sacrum that extend into the spinal canal (Denis zone III) as
      part of displaced, vertically stable anterior-posterior compression pelvic
      injuries, have a low incidence of neurologic deficit attributable to sacral root
      or plexus injury. This is in contrast to the high rate of neurologic deficit
      (>50%) otherwise reported in zone III sacral fractures, particularly in those
      associated with a displaced transverse component. In the midline sagittal
      fracture variant, simultaneous lateral displacement of both bony and neural
      elements through the midline may protect the sacral roots and plexi from
      significant traction or shear injury by maintaining the spatial orientation
      between the sacral foramina and sciatic notch. Long-term sequelae were related to
      urogenital complaints rather than to musculoskeletal problems, as 4 of the 10
      patients in this series had either sexual or urologic dysfunction.

PMID- 12499966
TI  - Adult distal humeral metaphyseal fractures: epidemiology and results of
      treatment.
AB  - OBJECTIVES: To examine the epidemiology and results of treatment of fractures of
      the distal humeral metaphysis. DESIGN: Observational cohort study. SETTING: An
      orthopaedic trauma unit, which provides all the fracture care for a well-defined
      catchment population. PATIENTS/PARTICIPANTS: A consecutive series of 320 patients
      with distal humeral fractures admitted to the unit between January 1988 and June
      1997. INTERVENTION: We adopted a protocol of open reduction and fixation of all
      displaced fractures (greater than 5 mm of displacement in any plane) in patients
      who were medically fit for anesthesia. Postoperative immobilization was a
      cylinder cast for 6 weeks. Patients with undisplaced fractures or who were
      medically unfit were also treated nonoperatively in cylinder casts for 6 weeks.
      MAIN OUTCOME MEASUREMENTS: Epidemiological examination of patient subgroups and
      the incidence of complications of treatment. RESULTS: The overall incidence of
      distal humeral fractures in adults during this time was 5.7 cases per 100,000 in
      the population per year with an almost equal male to female ratio. There was a
      bimodal age distribution, simple falls were the most common overall cause of
      fracture, and the majority of the fractures were extra-articular (AO/OTA type A)
      or complete articular fractures (AO/OTA type C). The risk of complications during
      treatment was generally low in most patients, and the majority healed their
      fractures uneventfully. Overall, 90.6% of fractures united within 12 weeks and
      just under half of the remaining 9.4% patients with union complications healed
      without requiring further operative intervention by 24 weeks. The risk of union
      complications was higher following high-energy injuries, open fractures, and
      nonoperative treatment. Although the AO/OTA classification was not predictive of
      union complications, the "low" transcondylar (type A2.3 and A3) and simple
      intercondylar fracture (type C1.3) configuration had a greater risk of union
      complications than the "high" subtype. The rate of infection, myositis
      ossificans, and other implant-related complications were higher following
      operative treatment of type C fractures than type A and B fractures. CONCLUSIONS:
      The epidemiology of a consecutive unselected series of adult distal humeral
      fractures is defined in this study. The majority of these fractures are best
      treated surgically by rigid open reduction and internal fixation, except for
      "low" Type A and C fractures, which have a higher risk of union complications.
      The role of total elbow arthroplasty to treat these more complex injuries
      requires further evaluation.

PMID- 12499967
TI  - Orthopedic injuries related to snowmobile use.
AB  - OBJECTIVES: To document the locations of injury, frequency of associated
      injuries, and need for operative intervention in patients presenting to a
      tertiary medical center after sustaining an orthopedic injury related to
      snowmobile use. DESIGN: Retrospective review. SETTING: Tertiary care center with
      level I trauma designation in southern Minnesota. PATIENTS/PARTICIPANTS: Seventy
      eight patients who sustained orthopedic injuries from snowmobile accidents
      between January 1985 and December 1996 were treated at our institution.
      Information regarding patient demographics and injury characteristics was
      collected. These data were stratified into patient populations presenting
      directly to the emergency department (n = 47) and those referred from outside
      hospitals (n = 31). RESULTS: A total of 209 injuries (118 fractures, 31
      orthopedic soft-tissue injuries, and 60 nonorthopaedic injuries) were diagnosed
      within the study population. Tibia (n = 20), radius (n = 14), ulna (n = 12), and
      spine (n = 14) fractures accounted for half of the fractures reported. There were
      13 open fractures. Twenty-four fractures were treated operatively. Ligament
      injuries to the knees (n = 7) and compartment syndrome of the lower extremity (n
      = 5) represented the most common orthopedic soft-tissue injuries. The
      acromioclavicular joint was the most frequently dislocated joint (n = 4).
      Associated injuries commonly involved the head (n = 17), abdomen (n = 13), and
      chest (n = 9). As compared to patients presenting directly to the emergency
      department, referred patients on average had a statistically greater number of
      total injuries, total operations, and operations for fractures. CONCLUSION:
      Snowmobile accidents represent a frequent cause of orthopedic injuries in
      northern regions. An understanding of these injuries may help emergency
      departments prepare for patients injured on these machines. Recognition of the
      most common orthopedic injuries may help in the design of safer snowmobiles.

PMID- 12499968
TI  - Mortality risk after hip fracture.
AB  - OBJECTIVE: To determine the mortality risk following hip fracture and identify
      factors predictive of increased mortality. DESIGN: Retrospective review of
      prospectively collected data. SETTING: Tertiary care orthopaedic hospital.
      BACKGROUND: Approximately 250,000 hip fractures occur annually in the United
      States. The greatest mortality risk following hip fracture has been demonstrated
      to be within the first 6 months of fracture, and some studies report that the
      risk approaches expected mortality after 6 months. However, more recent studies
      have demonstrated that an increased risk of mortality may persist for several
      years postfracture. The purpose of this study was to assess the excess mortality
      associated with hip fracture at up to 2 years postinjury. METHODS: All patients
      with a hip fracture who were admitted to our institution over a 10-year period
      were evaluated. Criteria for inclusion included: Caucasian, age 65 or older,
      previously ambulatory, and home dwelling. Patients were followed prospectively to
      determine the mortality risk associated with hip fracture over a 2-year follow-up
      period. Mortality was compared to a standardized population and standardized
      mortality ratios were calculated. RESULTS: Eight hundred thirty-six patients met
      the inclusion criteria and were included. The mortality risk was highest within
      the first 3 months following fracture, with standardized mortality ratios
      approaching that of the control population by two years. Patients age 65-84 had
      higher mortality risk when compared with patients age > or =85. American Society
      of Anesthesiologists classification was predictive of increased mortality risk in
      younger patients, with these patients having triple the mortality risk when
      compared to the reference population at 2-year follow-up. More elderly patients
      had minimal excess mortality associated with hip fracture at 1- and 2-year follow
      up, regardless of ASA classification. CONCLUSION: The data demonstrate that hip
      fracture is not associated with significant excess mortality amongst patients
      older than age 85. Amongst younger patients, however, those with ASA
      classifications of 3 or 4 have significant excess mortality following hip
      fracture that persists up to 2 years after injury.

PMID- 12499969
TI  - How does torsional deformity of the radial shaft influence the rotation of the
      forearm? A biomechanical study.
AB  - OBJECTIVE: The aim of this experimental study was to measure the exact influence
      of isolated torsional deformities at the middle third of the radial shaft on the
      rotation of the forearm. DESIGN: Biomechanical study in cadavers. SETTING: Trauma
      Surgery Research Laboratories at the Medical School of Hannover, Hannover,
      Germany. INTERVENTION: Fourteen intact and fresh cadaver specimens were fixed in
      a newly developed apparatus that allowed free pronation and supination. A ring
      fixator was applied to the radial shaft with K-wires that allowed us to stabilize
      torsional deformities in steps of 10 degrees. The middle of the radial shaft was
      osteotomized via a small soft tissue window, leaving the other soft tissues,
      including the interosseous membrane, intact. MAIN OUTCOME MEASUREMENT: Supination
      and pronation were measured using a goniometer in a standardized fashion.
      RESULTS: The mean (standard deviation) supination value before osteotomy of the
      radius was 71.6 degrees (15.2 degrees), and the mean (standard deviation)
      pronation value was 64.5 degrees (12.4 degrees). Radial osteotomy caused no
      significant difference in the range of motion before creation of torsional
      deformities. Supination torsional deformities >30 degrees showed a significant
      loss of pronation. In turn, pronation torsional deformities >30 degrees resulted
      in a significant loss of supination. The amount of mean rotational loss was
      approximately the same in the respective pronation and supination torsional
      deformities. CONCLUSION: An axial torsional deformity of the radius of >30
      degrees causes a statistically significant loss of forearm rotation in fresh
      cadavers.

PMID- 12499970
TI  - External fixation with standard AO-plates: technique, indications, and results in
      31 cases.
AB  - The standard AO-plate was used as an external fixator in 31 patients with an
      infected nonunion or open fracture mainly of the upper extremity. With the use of
      this technique, good stability can be achieved with an inexpensive and relatively
      simple construction. The low profile of the frame is an advantage for the
      patient.

PMID- 12499971
TI  - Open anterior-inferior hip dislocation.
AB  - Traumatic hip dislocations result from high-energy trauma. These dislocations are
      usually posterior in direction and have severe associated injuries. The less
      common anterior dislocation is usually of the inferior type. We report a case of
      an open anterior-inferior hip dislocation secondary to a high-speed motor vehicle
      collision. The wound was in the medial upper ipsilateral thigh. To our knowledge,
      this is the first reported case of an adult with an open inferior-type anterior
      hip dislocation.

PMID- 12499972
TI  - Bilateral peroneal nerve palsy following emergent stabilization of a pelvic ring
      injury.
AB  - External noninvasive compressive devices are becoming popular for emergent
      stabilization of pelvic ring disruptions. The ease of application utilizing
      available materials such as sheets, the noninvasive nature of such measures, and
      perceived absence of complications has made this a popular stabilization
      modality. The authors report a case of bilateral peroneal nerve palsy related to
      the use of external compressive wraps in a patient with pelvic ring injury.

PMID- 12499973
TI  - Pseudoaneurysm of the inferior gluteal artery following polytrauma: diverse
      presentation of a dangerous complication: a report of two cases.
AB  - Gluteal artery aneurysms are rare, and the majority of them are pseudoaneurysms
      secondary to blunt or penetrating trauma. The superior gluteal artery is normally
      affected. Inferior gluteal artery pseudoaneurysms are uncommon, and review of the
      literature revealed only 10 cases in the last 30 years. The mainstay of diagnosis
      is angiography, but these aneurysms may not be visible on an aortic flush
      angiogram, and super selective angiography may be required to delineate the
      anatomy. Treatment is either by surgical therapy or minimally invasive
      techniques, such as embolization, during angiography. We report two cases of
      pseudoaneurysms of the inferior gluteal artery following pelvic and acetabular
      trauma, presenting very differently in time and clinical picture. A review of the
      relevant literature is also presented.

PMID- 12499974
TI  - Anatomic assessment of the proper insertion site for a tibial intramedullary
      nail.

PMID- 12499975
TI  - Intraoperative monitoring of brain tissue oxygen and carbon dioxide pressures
      reveals low oxygenation in peritumoral brain edema.
AB  - Brain edema and swelling often complicate surgery for brain tumors. Its
      pathophysiology is unclear, as is the relationship with brain tissue oxygenation.
      Our hypothesis was that brain edema around tumor is cytotoxic type caused by
      impaired local tissue oxygenation due to increased local tissue pressure.
      Therefore, we monitored brain tissue oxygen pressure (p(ti)O2) and carbon dioxide
      pressure (p(ti)CO2) in 19 patients undergoing craniotomy for removal of a brain
      tumor and specifically studied the effect of decompression by dura opening and by
      tumor removal with respect to the presence of brain swelling. Before craniotomy,
      multiparameter sensors were inserted into the peritumoral brain tissue guided by
      MRI-based stereotaxy. In eight patients who had severe brain swelling upon
      opening of the dura mater, p(ti)O2 immediately rose from 7 +/- 8 mm Hg to 24 +/-
      15 mm Hg ( < 0.05), whereas in patients who did not have swelling, p(ti)O2 went
      from 16 +/- 9 to 18 +/- 10 mm Hg after opening of the dura. The mean p(ti)O2 of
      all patients at the start of resection of the tumor was 18 +/- 11 mm Hg, and
      increased to 30 +/- 15 mm Hg after resection was completed ( < 0.05). The effect
      on p(ti)O2 of raising the FiO2 to 1.0 was limited in this group of patients, as
      an increase greater than 50% was found in only six of twelve patients. Notably,
      in six patients, sensor malfunctions or associated hardware problems occurred,
      prohibiting useful data acquisition. We conclude that brain tissue oxygenation is
      reduced in the peritumoral area and improves after local tissue pressure relief,
      especially in patients with brain swelling. Thus, ischemic processes may
      contribute to brain edema around tumors. Intraoperative p(ti)O2 monitoring may
      enhance the safety of neuroanesthesia, but the high incidence of failures with
      this type of sensor remains a matter of concern.

PMID- 12499976
TI  - Evaluation of the safety of recent surgical microscopes equipped with xenon light
      sources.
AB  - Although recent surgical microscopes for neurosurgery are equipped with xenon
      light sources to obtain bright fields of vision, the safety of a xenon beam,
      which has strong energy intensity in a long ultraviolet light, for cortical
      neurons has not been evaluated. Cranial windows were made in the parietal bones
      of gerbils. The skull of each gerbil was covered with warmed saline (0.5 mm in
      depth) to maintain the brain temperature. Ultraviolet irradiation (365-nm) was
      performed for 30 minutes at energy levels of 9.6, 4.4, 1.3, and 0.3 mwatts/cm(2),
      and neuronal damage was observed in 90 +/- 4%, 42 +/- 23%, 9 +/- 6%, and 0 +/- 0%
      of pyramidal cells in the parietal cortex 24 hours later. With the use of a
      logistic regression curve, the energy level causing 50% of neuronal damage was
      estimated to be 5.4 mwatts/cm(2). By increasing the thickness of the saline layer
      over the skull surface (1 mm and 2 mm), neuronal damages were significantly
      attenuated (21 +/- 18% and 10 +/- 8%, respectively, 4.4 mwatts/cm(2). Because the
      highest energy levels of 365-nm ultraviolet rays emitted from surgical
      microscopes measured in the present study (0.379 mwatts/cm (2)) were much closer
      to the dose causing 0% damage than to the dose causing 9% damage, the risk of
      neuronal injury occurring during microsurgery could be negligible. However, care
      should be taken in patients who take medicine classified as photosensitizing
      agents, such as diphenylhydantoin, which are thought to concentrate ultraviolet
      energy. The use of saline over the cortical surface may be beneficial for
      reducing the detrimental effects of 365-nm ultraviolet light.

PMID- 12499977
TI  - Clotting onset time may be a predictor of outcome in human brain injury: a pilot
      study.
AB  - In this study we assess the clotting onset time (COT) in samples from a
      population of traumatic brain injury patients. The patients were randomized to
      standard treatment plus high dose antithrombin (AT group) or standard treatment
      alone (nonAT group), during the first 16 hours after hospital admission. Our aim
      was to study the two patient groups during the first 5 days after injury, to
      assess COT as a coagulation monitoring method compared to routine parameters
      (thrombin-antithrombin complex (TAT), D-dimer, and soluble fibrin), and to
      correlate COT to clinical parameters and outcome. Clotting onset time
      measurements are carried out using free oscillating rheometry, where the endpoint
      of coagulation onset is determined by a deviation from initial viscoelastic
      properties of an oscillating sample. Both patient groups initially showed
      hypercoagulation. In the AT group, a significant increase of COT (i.e., decrease
      in hypercoagulation), was already seen 16 hours after hospital admission, but not
      until day 3 in the non AT group. Routine coagulation tests were not able to
      discriminate AT patients from nonAT patients. Clotting onset time correlated
      significantly to soluble fibrin, D-dimer, TAT, and leukocyte count. Additionally,
      COT levels at hospital admission correlated to outcomes measured with the Glasgow
      Outcome Scale (GOS) after 3 months. These results indicate that COT may be a
      clinically relevant variable with prognostic value, able to monitor the degree of
      hypercoagulation over time.

PMID- 12499978
TI  - Visual evoked potentials for intraoperative neurophysiologic monitoring using
      total intravenous anesthesia.
AB  - Conflicting reports on the usefulness of intraoperative monitoring of visual
      function by means of visual evoked potentials (VEPs) initiated this study. In 32
      patients without visual problems, VEPs were recorded to evaluate the reliability
      for intraoperative monitoring with total intravenous anesthesia. All patients
      underwent noncranial surgery. Using a standard technique, VEPs were recorded
      preoperatively in the awake patients and after induction of anesthesia during
      surgery. A total of 1436 intraoperative traces were recorded and analyzed. A
      minor prolongation of the P100 latency of 8% and a more pronounced attenuation of
      the P100-N145 amplitude of 60% were observed in the anesthetized patients. In
      most of the anesthetized patients, a stable recording of VEPs was not obtainable.
      In 4 patients (12.5%), clearly identifiable VEP peaks were detected in more than
      90% of the traces recorded intraoperatively. In 88% of the patients, reproducible
      VEPs were obtained in less than 75% of the intraoperative traces only. We
      concluded that with standard recording techniques and total intravenous
      anesthesia, intraoperative VEP monitoring in surgically anesthetized patients is
      not reliable.

PMID- 12499979
TI  - Decompressive craniectomy for intractable cerebral edema: experience of a single
      center.
AB  - Several case reports and small clinical series have reported benefits of
      decompressive hemicraniectomy in patients with intractable cerebral edema and
      early clinical herniation. Specific indications and timing for this intervention
      remain unclear. We present our experience with this procedure in a subset of 18
      patients with massive cerebral edema refractory to medical management, treated
      with decompressive craniectomy over a 3-year period (1997 to 2000). Computerized
      tomography (CT) scans were independently analyzed by a neuroradiologist blinded
      to clinical outcome. Eleven male and seven female patients, ages 20 to 69 years
      (mean +/- SEM, 46 +/- 14 years), underwent hemicraniectomy for the following
      diagnoses: 12 hemispheric infarcts, 3 traumatic intracerebral
      hemorrhages/contusions, 2 nontraumatic intraparenchymal hemorrhages (ICH), and 1
      subdural empyema. This population included four patients with aneurysmal
      subarachnoid hemorrhage (SAH). Patients were followed for a mean of 10 months.
      Clinical factors including age, side of lesion, preoperative herniation signs,
      and early surgery (<12 or <24 hours) were not significantly associated with
      mortality or Glasgow outcome score (GOS). Preoperative CT evidence of
      transtentorial herniation (present in 5/17 patients) was associated with
      mortality ( = 0.04), while preoperative uncal herniation (8/17 patients) was
      associated with poor outcome (GOS > 1) ( = 0.01). Favorable outcome (GOS > 3)
      occurred in six patients, three with spontaneous or traumatic focal hematomas. Of
      four patients with SAH, one died while the others were severely disabled (GOS 3).
      Seven of nine patients with malignant MCA infarctions unrelated to SAH had poor
      outcomes. The overall mortality was 4/18 (22%). Patients with refractory cerebral
      swelling secondary to focal hematomas may have better outcomes following
      decompressive craniectomy. Patients with preexisting SAH seem to have poor
      outcomes, possibly related to other neurologic comorbidities. Hemicraniectomy
      requires definition of proper timing. Preoperative CT findings, especially
      transtentorial and uncal herniation may be useful in defining when decompressive
      surgery should not be performed.

PMID- 12499981
TI  - Traumatic rupture of external carotid artery: report of emergency treatment with
      Guglielmi detachable coil.
AB  - Carotid dissection is a major complication of blunt head and neck trauma. The
      authors describe a case report of sudden bleeding of a distal branch of the
      external left carotid artery caused by a fracture of the mandible. This event
      occurred a week after the trauma. After a first phase consisting in
      cardiopulmonary resuscitation and blood loss replacement, the placement of a
      Guglielmi detachable coil (GDC) was considered the best and safest way to stop
      the bleeding. Guglielmi detachable coil represents a good technique for emergency
      treatment of bleeding from distal carotid vessels. Given its high cost, the
      diagnostic study of vessels near mandible fractures should not be considered as
      routine in cases of head and neck trauma, but should be considered in the
      presence of local hemorrhage or suspicious neurologic signs.

PMID- 12499980
TI  - Brain tissue oxygen monitoring for assessment of autoregulation: preliminary
      results suggest a new hypothesis.
AB  - Brain tissue oxygen monitoring (P(ti)O2 (Neurotrend, Codman, Germany) was
      employed in addition to standard intracranial pressure (ICP) and cerebral
      perfusion pressure (CPP) monitoring in seven patients with severe neuronal damage
      of heterogeneous etiology. The correlation between P(ti)O2 changes and CPP
      fluctuations during periods of 30 minutes were analyzed, when CPP was above 70
      mmHg and lower than 100 mmHg. A new ratio, the CPP-oxygen-reactivity (COR) index
      was calculated as COR=delta p(ti)O2 %/delta CPP%. The patient COR values were
      compared to those found in the brain of six noninjured anesthetized piglets. The
      analysis was performed to determine the significance of synchronous fluctuations
      of CPP and P(ti)O2, when CPP is above the lower threshold of autoregulation. The
      correlation between CPP variations and p(ti)O2 variations was found to be strong
      (R(mean)) = 0.74 +/- 0.17) in the patients and was weak in the uninjured animals
      (R(mean)) =0.38 +/- 0.43). The COR (mean) was 2.05 +/- 0.57 in patients and 0.78
      +/- 0.6 in the animals. In the injured brain of our patients, we observed an
      unexpectedly close correlation between P(ti)O2 and CPP variations when CPP levels
      were within a therapeutically targeted range (70 to 100 mmHg). In a porcine
      model, we could not find this relationship in the noninjured brain. We speculate
      that an increased COR might be indicative for an impaired local pressure
      autoregulation. The preliminary data suggest that COR values above "1" might be
      pathologic. However, the reported sample sizes are too small to provide
      sufficient statistical power to justify inferential statistical analyses. As
      such, results are presented with descriptive statistics only, and should be
      regarded as a hypothesis.

PMID- 12499982
TI  - Subdural hematoma as a late complication of spinal anesthesia.
AB  - Subdural hematoma is a rare complication of spinal anesthesia. This patient
      underwent bilateral inguinal herniorrhaphy under spinal anesthesia 40 days prior
      to admission. Two days after spinal anesthesia, the patient described a typical
      postdural puncture headache. Oral analgesics, fluid therapy, and lying flat were
      recommended. Because of prolonged headache, computed tomography scan was
      performed and demonstrated chronic subdural hematoma in the left fronto-temporo
      parietal region. After surgical drainage, the patient fully recovered. Prolonged
      headache should be regarded as a warning sign of subdural hematoma.

PMID- 12499983
TI  - Propofol increased cerebral perfusion as compared with isoflurane during a
      cerebral angiography in a child with moyamoya disease.
AB  - We report the case of a child with Moyamoya disease during a cerebral angiography
      procedure in which the effects of propofol on the cerebral perfusion were seen to
      be different compared with isoflurane. We suggest propofol was associated with a
      better preservation of cerebral circulation compared to isoflurane in this case
      of Moyamoya, as it maintained blood supply to the watershed areas.

PMID- 12499984
TI  - Placing nasogastric tubes and intracranial pressure.
AB  - Recently, a new method for placing nasogastric tubes (NGT) in dysphagic patients
      was proposed, which uses the swallowing reflex and was therefore called 'reflex
      placement.' The authors describe the use of this method in a patient with a large
      left sided striatocapsular hemorrhage, in whom decompressive craniotomy had been
      performed previously. Whereas the conventional approach of placing NGT led to a
      massive increase of intracranial pressure (ICP) and to a decline in cerebral
      perfusion pressure (CPP), the new method allowed a swift placement with only
      minor changes of ICP and CPP. The strict avoidance of intermittent peaks of ICP
      constitutes a basic principle of care in patients with space occupying brain
      lesions. We therefore suggest that, despite the admittedly larger effort, the
      reflex placement of NGTs should be used in such circumstances.

PMID- 12499986
TI  - Endovascular treatment for cerebral aneurysms will replace clipping.

PMID- 12499987
TI  - Microsurgery and clipping: the gold standard for the treatment of intracranial
      aneurysms.

PMID- 12499990
TI  - Tissue transglutaminase: master regulator of celiac disease?

PMID- 12499989
TI  - The epidemiology of Helicobacter pylori: where to from here?

PMID- 12499991
TI  - Linear programming: a mathematical tool for analyzing and optimizing children's
      diets during the complementary feeding period.
AB  - During the complementary feeding period, children require a nutrient-dense diet
      to meet their high nutritional requirements. International interest exists in the
      promotion of affordable, nutritionally adequate complementary feeding diets based
      on locally available foods. In this context, two questions are often asked: 1) is
      it possible to design a diet suitable for the complementary feeding period using
      locally available food? and 2) if this is possible, what is the lowest-cost,
      nutritionally adequate diet available? These questions are usually answered using
      a "trial and error" approach. However, a more efficient and rigorous technique,
      based on linear programming, is also available. It has become more readily
      accessible with the advent of powerful personal computers. The purpose of this
      review, therefore, is to inform pediatricians and public health professionals
      about this tool. In this review, the basic principles of linear programming are
      briefly examined and some practical applications for formulating sound food-based
      nutritional recommendations in different contexts are explained. This review
      should facilitate the adoption of this technique by international health
      professionals.

PMID- 12499992
TI  - Dietary threonine reduces plasma phenylalanine levels in patients with
      hyperphenylalaninemia.
AB  - BACKGROUND: In order to achieve normal intellectual development, the plasma phe
      nylalanine (PHE) levels of patients with hyperphenylalaninemia should not exceed
      toxic levels. This goal is usually accomplished by employing special diets in
      which the patient's protein intake is in the form of PHE-free mixtures of amino
      acids. There is evidence from our own observations in animals and a preliminary
      observation in patients with hyperphenylalaninemia that supplemental dietary
      threonine (THR) might decrease plasma PHE concentrations. METHODS: In this
      placebo-controlled crossover study, the effect of supplemental oral THR on the
      plasma amino acid concentrations of 12 patients with hyperphenylalaninemia was
      investigated. Before starting the first treatment period of this cross-over
      study, the patients were randomly assigned to one of two groups supplemented
      either with approximately 50 mg THR/kg per day or with a similar amount of
      maltodextrin as placebo. After a feeding period of 8 weeks and a wash-out period
      of 8 weeks, the supplements were crossed over and the study continued for an
      additional 8 weeks. Blood was obtained at the start and the end of each
      supplementation period. RESULTS: Dietary THR supplementation of approximately 50
      mg/kg per day resulted in a significant decrease of plasma PHE levels ( P =
      0.0234). There was a close positive correlation between plasma and urinary PHE
      concentrations ( P < 0.001) indicating that the lower plasma PHE levels in the
      THR supplemented patients were not caused by higher urinary excretion of PHE.
      CONCLUSIONS: The data of the present study show that oral THR supplementation has
      a clear plasma-PHE-reducing effect but they do not allow any conclusion about the
      mechanisms responsible for the observed effect. Although it seems attractive on
      the basis of the present data to use THR supplementation in patients with
      hyperphenylalaninemia, the mechanism of the observed effect should be clarified
      before introduction of such a treatment in these patients.

PMID- 12499993
TI  - Predictors of cobalamin deficiency in Guatemalan school children: diet,
      Helicobacter pylori, or bacterial overgrowth?
AB  - OBJECTIVES: The authors investigated whether low vitamin B12 intake, impaired
      gastric function, infection, and bacterial overgrowth were risk factors for the
      high prevalence of cobalamin deficiency observed in Guatemalan children. METHODS:
      The plasma cobalamin concentration of 556 school children was measured and
      classified as low, marginal, or adequate. In 60 children from each of these three
      groups, concentrations of serum methylmalonic acid (MMA), plasma homocysteine,
      and plasma holotranscobalamin II were measured, and usual dietary B12 intake was
      estimated. Serum gastrin and pepsinogen I concentrations were measured, and and
      bacterial overgrowth were diagnosed using C-urea and C-xylose breath tests,
      respectively. RESULTS: infection was present in 83% (144 of 174) of children, and
      bacterial overgrowth was found in 25% (28 of 113). Children with infection had
      higher serum gastrin and pepsinogen I. There were no significant differences
      among the plasma cobalamin groups in the prevalence of infection, bacterial
      overgrowth, serum gastrin, or pepsinogen I concentrations. However, there was a
      significant positive correlation between serum MMA and gastrin concentrations.
      The average daily consumption of dietary B12 was 5.5 +/- 5.2 microg/day, but
      intakes for 23% of children were <1.8 micro g/day. B12 intake from fortified
      snacks added an additional 0.3 +/- 0.2 microg/day. B12 intake was not
      significantly different among the plasma cobalamin groups, but it was
      significantly correlated with plasma cobalamin. CONCLUSIONS: The specific cause
      of cobalamin deficiency in this population remains unclear, but these results
      suggest that low dietary B12 intake is a risk factor and alterations in gastric
      secretions may also play a role.

PMID- 12499995
TI  - Slight decrease in bone mineralization in cow milk-sensitive children.
AB  - BACKGROUND: Patients with cow milk allergy (CMA) are potentially at risk for
      osteopenia because their milk-free diet usually contains a low calcium content.
      In our study, different parameters of bone mineralization in children with CMA
      were investigated. PATIENTS AND METHODS: Twenty-seven CMA patients (mean age, 4.3
      years; range, 3-8 years) were enrolled in the study. During a mean milk-free diet
      period of 11.8 months, children were fed extensively hydrolyzed or soy-based
      formulas. After a milk challenge test, 7 patients showed allergic symptoms, and
      the other 20 children had transient CMA. From the sera of all patients, the
      levels of sodium, potassium, chloride, calcium, phosphate, and magnesium ions, as
      well as alkaline phosphatase (AP), parathyroid hormone (PTH), osteocalcin, and
      beta-crosslaps, were determined. These values were compared with those of 20
      healthy age-matched controls. Bone mineral density was measured as well. RESULTS:
      The AP and PTH concentrations were higher in CMA patients than in the control
      group (AP: 610.2 U/L vs. 499.7 U/L, P < 0.01; PTH: 1.56 pmol/L vs. 0.83 pmol/L,
      P< 0.03), but all values were in the normal range. The osteocalcin concentration
      was similar in both groups, and the beta-crosslaps concentration was lower in CMA
      patients than in controls (0.92 vs. 1.47 ng/mL, P< 0.001). The mean Z score of
      bone mineral density in patients with CMA was -0.6. In 10 cases, the Z score was
      less than the -1 SD value. On the basis of the Z score, CMA patients were divided
      into two groups. The PTH concentration was significantly elevated in the group
      with lower Z score (2.24 pmol/L vs. 1.16 pmol/L; P< 0.03). CONCLUSION: The
      results suggest that, in children with CMA who are on a cow milk-free diet,
      slight disturbances of bone mineralization can be observed by osteodensitometry.

PMID- 12499994
TI  - Effect of nucleotides on diarrhea and immune responses in healthy term infants in
      Taiwan.
AB  - OBJECTIVES: The aim of this study was to compare the effects of an infant formula
      fortified with nucleotides (NF) with those of a control formula (CF) on the
      incidence of diarrhea, respiratory tract infections (RTIs), and immune responses
      in healthy term infants. METHODS: This 12-month, double-blind study was conducted
      on 1- to 7-day-old infants randomized to receive NF or CF exclusively until 12
      weeks of age, and fed the assigned formula with solid food until 12 months. NF
      was supplemented with 72 mg/L of nucleotides, based on the total potentially
      available nucleotide content of human milk. Subjects were evaluated within 1 week
      of birth, at 4 weeks, and every 4 weeks thereafter until 48 weeks of age. The
      primary outcome variable was the incidence of diarrhea. Secondary variables
      included RTIs, serum immunoglobulin concentrations, and response to hepatitis B
      vaccine. RESULTS: Compared with subjects fed CF (n = 170), those fed NF (n = 166)
      had a trend toward reduced risk of diarrhea from 8 to 48 weeks of age and a
      significantly lower risk of 25.4% (P = 0.05) between 8 and 28 weeks. NF subjects
      had significantly higher serum immunoglobulin A concentrations ( P < 0.05)
      throughout the 48-week study. The NF group had an increased risk of upper RTIs,
      the same incidence of lower RTIs, and the same antibody response to hepatitis B
      vaccination as the CF group, based on one-sided tests. Growth was normal in both
      groups, and no adverse events were considered to be formula-related. CONCLUSIONS:
      Healthy term infants from 8 to 28 weeks of life are less likely to experience
      diarrhea and have higher serum immunoglobulin A concentrations with NF compared
      with formula without added nucleotides.

PMID- 12499996
TI  - Lack of cholesterol-lowering effect of graded doses of cholestyramine in children
      with Alagille syndrome: a pilot study.
AB  - BACKGROUND: There is controversy about the potential risk of sustained high
      concentrations of cholesterol and triglyceride in patients with cholestatic
      chronic liver disease. However, it is currently accepted that cholesterol
      lowering therapy may reduce morbidity and mortality rates in hypercholesterolemic
      patients without preexisting coronary heart disease, as well as in those with
      coronary heart disease. The objective of this study was to evaluate the effect of
      cholestyramine on the serum lipid profile of a group of children with Alagille
      syndrome and hypercholesterolemia. METHODS: Five children with Alagille syndrome
      and basal serum cholesterol concentrations greater than 230 mg/dL were included.
      Total serum cholesterol, triglyceride, low-density, and high-density lipoprotein
      cholesterol concentrations were measured on days 0, 10, 20, and 30 after the
      administration of oral cholestyramine 100, 250, and 500 mg(kg.d), respectively.
      Lipid fractions were reported as mean +/- 1 SD. Statistical analysis was
      performed with Friedman analysis of variance. RESULTS: The basal values and those
      of the three 10-day subsequent 100-, 250-, and 500-mg(kg.d) cholestyramine
      periods were as follows: total cholesterol: 327.6 +/- 77.1, 305.4 +/- 52.1, 290.6
      +/- 24.1, and 320.6 +/- 32.3, respectively (P = 0.668); triglyceride: 136.4 +/-
      14.6, 144.8 +/- 41.3, 161 +/- 30.9, and 165.4 +/- 40.7, respectively (P = 0.356);
      low-density lipoprotein cholesterol: 245.4 +/- 57.8, 239.8 +/- 48.6, 242.2 +/-
      68.6, and 246.4 +/- 49.5, respectively (P = 0.782); and high-density lipoprotein
      cholesterol: 44.4 +/- 11.2, 41.8 +/- 12.8, 44.6.2 +/- 13.2, and 47 +/- 8.5,
      respectively (P = 0.431). CONCLUSION: Under the conditions of the current study,
      no significant effect of variable doses of cholestyramine could be demonstrated
      on the serum lipid profile of a series of children with Alagille syndrome. While
      the controversy on the potential atherogenic risk of low-density lipoprotein
      hypercholesterolemia in patients with chronic liver disease persists, new,
      prospective pharmacologic or nutritional trials are required.

PMID- 12499997
TI  - The spectrum of fatty liver in obese children and the relationship of serum
      aminotransferases to severity of steatosis.
AB  - OBJECTIVES: Non-alcoholic fatty liver disease is an emerging diagnosis in the
      pediatric population. Previously, ultrasonography and serum aminotransferases
      have been used to estimate prevalence of the disorder. A lack of concordance has
      been noted between these two diagnostic tests. To better understand the spectrum
      of fatty liver in obese children and the relationship of serum aminotransferases
      to the severity of steatosis, hepatic MRI was used to quantitate fat content.
      METHODS: Twenty-two children, ages 6 to 18 years, with obesity (BMI > 95th
      percentile for age) and hepatomegaly (liver edge more than 2 cm below the right
      costal margin) underwent hepatic MRI for fat quantitation. Hepatic MRI was
      performed using a modification of the Dixon method that used a fast gradient echo
      sequence rather than traditional spin echo. Scan times were sufficiently brief to
      allow completion within a single breath hold. Serum aminotransferases were
      obtained within one month of MRI. RESULTS: Twenty-one of 22 subjects had an
      elevated hepatic fat fraction. Seven of 7 subjects with a fat fraction of < or
      =18% had a normal serum ALT. Twelve of 13 subjects with fat fraction of >18% had
      an elevated serum ALT. Hepatic fat fraction correlated with serum ALT but did not
      correlate with age, BMI, or serum AST. CONCLUSION: The spectrum of fatty liver is
      larger than detected by screening for abnormal serum aminotransferases alone.
      Abnormalities in serum ALT occur exclusively in more severe cases of fatty liver.

PMID- 12499998
TI  - Glycine conjugation of para-aminobenzoic acid (PABA): a pilot study of a novel
      prognostic test in acute liver failure in children.
AB  - BACKGROUND: Fulminant hepatic failure (FHF) is associated with high mortality;
      few patients survive without liver transplantation. It is important to have a
      sensitive, specific early predictor of outcome to distinguish potential survivors
      (S) from nonsurvivors (NS). OBJECTIVE: Because we had previously shown that
      glycine conjugation of para-aminobenzoic acid (PABA) quantitatively reflects
      liver function in children with chronic liver disease, in this pilot study we
      wanted to determine whether the measurement of the glycine conjugates of PABA
      could distinguish S from NS in FHF in comparison with standard prognostic
      indices. METHODS: Twenty-four patients were studied: acute severe hepatitis (n =
      7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's
      College criteria, measurement of factor V and VII levels, PABA testing, and
      transjugular liver biopsies were performed in almost all patients within 48 hours
      of admission. Serum PABA and its glycine conjugates (para-aminohippurate (PAHA)
      and para-acetamidohippurate (PAAHA)) were measured thirty minutes after oral
      administration by high-pressure liquid chromatography. Poor prognostic categories
      as previously established in the literature were defined as factor V < 0.20U/ml,
      factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M.
      RESULTS: The measurement of PAHA was the best predictor of a poor outcome in
      patients with acute liver failure with a sensitivity of 92%, and negative
      predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63%
      with King's College criteria. CONCLUSION: Measurement of serum PAHA is the best
      early prognostic marker of death in children who suffer from FHF.

PMID- 12499999
TI  - Helicobacter pylori seropositivity among adolescents in Novosibirsk, Russia:
      prevalence and associated factors.
AB  - OBJECTIVES: We have reported previously that infection is widespread among adults
      in Siberia, in whom prevalence rates range from 70% to 90%. The present study was
      undertaken to determine the seroprevalence of infection and its relation to
      social factors in a community-based population of adolescents in Novosibirsk,
      Western Siberia. METHODS: All students in forms 9 to 11 of four randomly selected
      secondary schools participated. A total of 423 students (180 boys, 243 girls;
      age, 14-17 years) completed structured questionnaire concerning their lifestyle,
      and sera were tested for using enzyme-linked immunosorbent assay (Pyloriset -New
      EIA-G; Orion Diagnostica, Finland). Personal information, including parental
      history, educational level, occupation, and smoking habits, were collected via a
      questionnaire. RESULTS: Overall, the seroprevalence of infection was 56.3%. Age,
      sex, smoking, alcohol consumption, number of children and pets in the household,
      and family history of gastric diseases were not associated with positivity. The
      predictors of infection were dwelling without running hot water supply and sewage
      (odds ratio [OR] = 2.4; 95% confidence interval [CI], 1.2-4.8), father's
      occupation as a manual worker (OR = 2.7; 95% CI, 1.5-5.0), mother's occupation as
      a manual worker (OR = 1.8; 95% CI, 1.0-3.0), father's lower educational
      attainment (OR = 2.1; 95% CI, 1.2-3.6), and father's smoking (OR = 1.8; 95% CI,
      1.1-3.2). CONCLUSIONS: The prevalence of seropositivity among adolescents in
      Russia is higher than in developed countries. The infection is associated with
      lower socioeconomic status.

PMID- 12500000
TI  - Tissue transglutaminase immunoglobulin isotypes in children with untreated and
      treated celiac disease.
AB  - OBJECTIVES: Tissue transglutaminase (tTG) autoantibodies are serologic markers
      for celiac disease (CD). The aim was to determine the diagnostic sensitivity and
      specificity of different immunoglobulin isotypes against tTG. METHODS:
      Immunoglobulin A (IgA)-tTG, IgG-tTG, and IgG1-tTG were measured in radioligand
      binding assays in 67 children with untreated and 89 children with treated CD and
      compared with 48 biopsy controls. IgM-tTG was measured in children with untreated
      CD and in biopsy controls. IgA endomysial autoantibodies (EMA) were analyzed in
      all children using an immunofluorescence method. RESULTS: The sensitivity of IgA
      tTG and IgG-tTG was 85.1% (57 of 67) and 83.6% (56 of 67), respectively, which
      both increased to 93.8% (45 of 48) in children diagnosed at age 2 years or older.
      Both had a specificity of 93.8% (45 of 48). IgA-EMA had a sensitivity of 80.6%
      (54 of 67) and a specificity of 91.7% (44 of 48). In treated CD, IgA-tTG and IgG
      tTG were detected in 21.3% (19 of 89) and in 14.6% (13 of 89), respectively,
      despite negative EMA titers. IgG1-tTG was correlated to age (r = -0.47, P =
      0.0005) and detected in 50.7% (34 of 67) with untreated CD compared with 11.2%
      (10 of 89) with treated CD and with 4.2% (2 of 48) of biopsy controls ( P <
      0.0001, respectively). IgM-tTG was detected in 1.5% (1 of 67) with untreated CD
      and in none of biopsy controls. CONCLUSION: IgA-tTG and IgG-tTG analyzed in
      radioligand binding assays are equivalent to IgA-EMA as screening tests for CD
      during childhood, but an intestinal biopsy is still the method of choice to
      establish the diagnosis. Although IgG1-tTG was more common at young age of
      diagnosis, both IgG1-tTG and IgM-tTG had low specificity and sensitivity and may
      not be useful as screening tests for CD.

PMID- 12500001
TI  - Pediatric Crohn Disease Activity Index: responsive to short-term change.
AB  - BACKGROUND/AIMS: Despite documented feasibility, reliability, and validity, the
      Pediatric Crohn's Disease Activity Index (PCDAI) has yet to be demonstrated to be
      sensitive to change in the time frame of acute treatment trials. We evaluated
      short-term responsiveness and determined the minimal change in PCDAI score
      associated with a clinically meaningful improvement in disease activity. METHODS:
      Standardized effect size (SES) and standardized response mean (SRM) were
      calculated as measures of responsiveness among pediatric patients being treated
      for acute exacerbations of Crohn disease 1) in a regular clinical practice
      setting and 2) as part of a multicenter, randomized controlled trial (RCT).
      Receiver operating characteristic (ROC) curves were constructed to determine the
      minimal PCDAI score change associated with significant clinical improvement used
      as the gold standard in 1) physician global assessment of change and in 2) change
      in adult Crohn disease activity index (CDAI). RESULTS: Among responders, the SES
      and SRM of the PCDAI were 1.78 and 1.41 (95% CI: 0.89-1.92) and 2.10 and 1.95
      (95% CI: 1.70-2.20) in the clinical practice setting and RCT setting,
      respectively. The optimal minimal PCDAI change score associated with clinically
      significant change in physician global assessment was determined to be -12.5
      (sensitivity 83.3%, specificity 92.3%). In the RCT setting a change in PCDAI of 
      10 corresponded to a change in CDAI of not greater-than-or-equal 70 points.
      CONCLUSIONS: The PCDAI is responsive to improvement in disease activity in Crohn
      disease patients over a short interval. As such, the PCDAI is an appropriate
      instrument to use in pediatric acute treatment trials.

PMID- 12500002
TI  - A critical assessment of items on the Pediatric Crohn's Disease Activity Index.
AB  - OBJECTIVES: Questions have been raised about the discriminative value of the
      three laboratory items (hematocrit, erythrocyte sedimentation rate, and albumin)
      and three physical items (height, perirectal disease, and extraintestinal
      manifestations) included in the Pediatric Crohn's Disease Activity Index (PCDAI).
      The aim of this study was to analyze the value of these six "criticized" items to
      the discriminative properties of the PCDAI. METHODS: Data from 71 children with
      Crohn's disease visiting an outpatient clinic were analyzed. Physician global
      assessment of disease activity was used as the gold standard. A "basic index" was
      calculated by subtracting the score of the six criticized items from the score of
      the PCDAI calculated in the standard fashion. Multivariate logistic regression
      procedures identified which items significantly contributed to the "basic index".
      Receiver operating characteristic curves were produced comparing the standard
      PCDAI score to the "basic index" and a new "clinical index" which included only
      the criticized items truly contributing to the discriminatory ability of the
      "basic index". RESULTS: Logistic regression models identified only perirectal
      disease as contributing to the discriminative abilities of the basic index. The
      clinical index therefore consists of the three history items (abdominal pain,
      number of liquid stools, and general well-being), three physical examination
      items (weight loss, abdominal examination, and perirectal disease) and no
      laboratory tests. The clinical index had an area under the curve not
      significantly inferior to that of the original PCDAI (0.93 [95% confidence
      interval, 0.89-0.99] vs. 0.96 [95% confidence interval, 0.92-0.99]). CONCLUSIONS:
      A clinical index consisting of three history items and three physical examination
      items has an accuracy equal to the standard PCDAI in distinguishing children with
      disease in remission from those with a relapse.

PMID- 12500003
TI  - Experimentally induced gluten enteropathy and protective effect of epidermal
      growth factor in artificially fed neonatal rats.
AB  - BACKGROUND: A protective effect of breast-feeding against the development of
      celiac disease has been described, but the nature and effects of the actual milk
      components have not been established. Epidermal growth factor (EGF), a milk
      cytokine affecting the proliferation and differentiation of mucosal epithelial
      cells, was studied as to its potential protective effect on the damage of
      intestinal mucosa by gliadin in a model system. METHODS: Enteropathy was induced
      by gliadin in inbred AVN strain rat pups delivered by cesarean section, breast
      fed, or hand-fed a milk formula. All experimental groups were treated with
      interferon-gamma (1,000 U per animal, administered intraperitoneally) after
      birth. Gliadin (0.5 and 3 mg) was intragastrically administered to the pups on
      days 0 and 3, and a 30-mg challenge dose was given on day 20 (24 hours before the
      termination of the experiment). One group of artificially fed pups received EGF
      (100 ng/ml) continuously in the diet. RESULTS: Gliadin- and interferon-gamma
      treated formula-fed rat pups showed villus atrophy, increase of inflammatory
      cells, including CD4+ T lymphocytes in the lamina propria, and damage to
      epithelial tight junctions and the enterocyte brush border. Morphometrically, the
      villus height was significantly less than in other groups. Recombinant EGF was
      markedly increased in the epithelial cells of injured jejunum. The intestinal
      mucosa of gliadin- and interferon-gamma-treated pups kept on a EGF-supplemented
      artificial diet resembled that of breast-fed pups. CONCLUSION: Pathologic changes
      in jejunal mucosa (villus atrophy and inflammation) resembling gliadin-induced
      atrophy appeared on administration of interferon-gamma and gliadin to rat pups
      fed an artificial milk diet immediately after birth. Addition of EGF to the diet
      protected the rats against pathologic mucosal changes.

PMID- 12500004
TI  - Breath test using a single 50-mg dose of 13C-urea to detect Helicobacter pylori
      infection in children.
AB  - BACKGROUND: The 13C-urea breath test is an accurate, noninvasive method for the
      diagnosis of in adults. A dose of 75 to 100 mg of urea is generally used,
      especially in adults, but the optimal dose in children is still unknown. Our aim
      was to determine whether urea breath test performed with a single 50-mg dose of
      13C-urea was sufficient and accurate for diagnosing infection in children.
      METHODS: Consecutive children 4 to 14 years of age undergoing upper intestinal
      endoscopy to evaluate symptoms of recurrent abdominal pain were prospectively
      included. Exclusion criteria included use of antibiotics or proton pump
      inhibitors during the last month, gastric surgery, and previous eradication
      therapy. Reference criteria for diagnosis of infection were based on histology,
      culture, and serology. Urea breath test (TAU-KIT; Isomed, S.L., Madrid, Spain)
      was performed as follows: citric acid (Citral pylori) dissolved in 100 mL of
      water was initially given. Ten minutes later, a baseline exhaled breath sample
      was collected, and thereafter 50 mg of 13C-urea dissolved in 50 mL of water was
      given. A second breath sample was obtained 30 minutes later. Breath samples were
      analyzed by isotope ratio mass spectrometry. The endoscopist, the pathologist,
      the microbiologist, and the person responsible for reading the serology and the
      urea breath test were all unaware of status by the other diagnostic methods.
      RESULTS: One hundred children were included (40% males; mean age, 9.2 +/- 2
      years; mean weight, 33.9 +/- 12 kg). Based on the reference criteria, 45% were
      infected, 37% were not infected, and 18% were indeterminate. Sensitivity,
      specificity, positive predictive value, and negative predictive value were,
      respectively, 91% (95% confidence interval [CI], 79%-96%), 97% (95% CI, 86%-99%),
      98% (95% CI, 87%-91%), and 90% (95% CI, 76%-96%). Positive and negative
      likelihood ratios were of 33 and 0.09. Any cutoff point between 2 and 14 delta
      units had the same high diagnostic accuracy. The area under the receiver
      operating characteristic curve was 0.94. No adverse effects were reported.
      CONCLUSION: Urea breath test using 50 mg of urea is sufficient and accurate for
      the diagnosis of infection in children. Use of a small test dose significantly
      lowers the cost of the test.

PMID- 12500005
TI  - Limitations of probiotic therapy in acute, severe dehydrating diarrhea.
AB  - BACKGROUND: Recent studies have shown that probiotics, most commonly, may be
      useful in treating acute gastroenteritis. However, beneficial effects appear to
      be limited to a modest decrease in the duration of diarrhea. No studies have
      evaluated this therapy in moderate to severe dehydrating diarrhea in a metabolic
      facility. METHODS: Male children less than 2 years of age were admitted to a
      metabolic unit of the Department of Pediatrics at the Federal University of
      Bahia, Brazil, with moderate dehydration and were randomized in a double-blind,
      placebo-controlled fashion. Oral rehydration solution (ORS) was administered per
      protocol and either placebo or was given in combination with the ORS. Output of
      urine, stool, and vomitus was recorded along with stool weight, nude body weight,
      and standard laboratory assessments for hydration. RESULTS: There was no
      significant reduction in diarrhea duration and stool output in the group.
      However, Kaplan-Meier survival analysis demonstrated that, even in moderate to
      severe diarrhea, resolution of the illness occurred so rapidly, that
      statistically significant benefits of probiotic therapy could not be
      demonstrated. CONCLUSION: Our data implies that colonization must occur before
      benefits of probiotics can be realized. Probiotics are, therefore, likely to be
      of limited benefit in treating diarrheal illnesses of short duration such as
      viral enteritis. The beneficial effects of probiotics may be limited to
      prophylactic usage in high-risk populations.

PMID- 12500006
TI  - The clinical spectrum of duodenal polyps in pediatrics.
AB  - OBJECTIVES: The aim of this retrospective study was to determine the prevalence,
      clinical presentation, and histologic subclassification of duodenal polyps
      identified on endoscopy (EGD) in pediatric patients. METHODS: We performed an 18
      year retrospective study of all pediatric patients (< 21 years) with duodenal
      polyps diagnosed between 1983 and 2001 at The Johns Hopkins Children's Center.
      Our analysis includes a formal histologic evaluation of duodenal polyps either
      biopsied using cold-forceps or removed by snare cautery. RESULTS: Duodenal polyps
      were reported in 22 of 5766 EGDs (0.4%) performed in 16 (M:F; 1:1) patients with
      a mean (SD) age of 14.1 (5.1) years. Polyps were equal in both the Caucasian and
      African American population (adjusted ratio 1.2:1). The histologic subtypes
      included Adenomatous (42%), Brunner's gland hyperplastic (33%), hamartomatous
      (17%), and heterotopic gastric gland polyps (8%). The most frequent indication
      for EGD was surveillance in patients with polyposis syndromes; most of these
      patients were asymptomatic at the time of their EGD. In comparison, the most
      frequent indication for an EGD in patients without polyposis syndromes was
      abdominal pain and vomiting. CONCLUSIONS: Duodenal polyps are most frequently
      encountered in children with polyposis syndromes, most of whom are asymptomatic.
      In nonsyndromic patients, the most common histologic subtype is Brunner's gland
      hyperplastic polyp and presenting symptoms include abdominal pain and vomiting.

PMID- 12500007
TI  - Hair relaxers: a benign caustic ingestion?
AB  - BACKGROUND: Despite federally legislated safety regulations, caustic ingestions
      remain a significant problem in the pediatric population. The current standard of
      care for caustic ingestion includes upper gastrointestinal endoscopy in most
      cases. Hair relaxers are a common caustic ingestion at our institution, yet few
      data have been published describing the clinical or endoscopic outcome. We
      explored the relative frequency of hair relaxer ingestion, the incidence of
      associated upper gastrointestinal injury, and the adverse clinical sequelae
      resulting from these ingestions. METHODS: Consecutive caustic ingestions admitted
      to our institution between January 1990 and January 2001 were identified. The
      data were collected through retrospective physician chart review, were analyzed,
      and were pooled with the existing literature to evaluate for the presence of
      esophageal injury. RESULTS: 96 charts were reviewed, 29 (30%) of which were hair
      relaxer ingestions that underwent esophagogastroduodenoscopy; these ingestions
      served as our study cohort. The median age of the cohort was 14.0 months and
      patients were evenly divided in gender. The most common symptoms at presentation
      were drooling and emesis. At endoscopy, lip and oropharyngeal mucosa were most
      commonly affected. While six patients (20.7%) had Grade I esophageal mucosal
      injury and five patients (17.2%) had Grade I gastric mucosal injury, none had
      greater than Grade I mucosal damage. No adverse clinical events were identified.
      When our data were combined with all previously published cohort data, the
      findings were similar and no adverse clinical outcomes were reported.
      CONCLUSIONS: Hair relaxer is the most common childhood caustic ingestion
      presenting to our large metropolitan tertiary care center. Symptoms are common at
      presentation. However, despite the high pH of these products, no clinically
      significant esophageal or gastric mucosal injuries and no long-term sequelae were
      identified.

PMID- 12500008
TI  - Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced
      by epidermal growth factor.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal
      disease of premature infants. We have shown in previous studies that
      proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum
      of rats with experimental NEC and that epidermal growth factor (EGF) reduces the
      development of disease. Here we investigated whether the protective effects of
      EGF are a result of changes in ileal interleukin-18, interleukin-12 and/or
      antiinflammatory interleukin-10. METHODS: Newborn rats were artificially fed with
      either growth-factor-free rat milk substitute (RMS) or RMS supplemented with 500
      ng/mL EGF (RMS + EGF) and NEC was induced via exposure to asphyxia and cold
      stress. Cytokine expression and localization were assessed using reverse
      transcription real-time polymerase chain reaction and immunohistology/confocal
      microscopy. RESULTS: Enteral administration of EGF (RMS + EGF) decreased
      overproduction of interleukin-18 and increased interleukin-10 production in the
      ileum. Furthermore, increased interleukin-10 production was associated with up
      regulation of the transcription factor Sp1 in RMS + EGF rats. CONCLUSIONS: These
      data suggest that EGF may reduce NEC via increased interleukin-10 and decreased
      interleukin-18 and that EGF-mediated up-regulation of Sp1 may account for the
      increased interleukin-10.

PMID- 12500009
TI  - Pancreaticopleural fistula: a rare cause of massive pleural effusion.

PMID- 12500010
TI  - Isolated small bowel transplantation for tufting enteropathy.

PMID- 12500011
TI  - Resolution of chronic hepatitis B-associated autoimmune neutropenia with
      interferon-alpha therapy.

PMID- 12500012
TI  - Cardiopulmonary compromise associated with milk and molasses enema use in
      children.
AB  - OBJECTIVE: Constipation is a common childhood problem that frequently confronts
      pediatric practitioners. When enema treatment is indicated to treat constipation,
      milk and molasses enemas are sometimes used. Side effects and adverse outcomes
      have been described with many types of enemas, but not with milk and molasses.
      The purpose of this study is to describe five children who acutely decompensated
      after receiving milk and molasses enemas. METHODS: Retrospective review of the
      medical records of children with constipation who received milk and molasses
      enema with subsequent PICU admission at Cincinnati Children's Hospital Medical
      Center between 1994 and 2000. RESULTS: Five children developed significant
      hemodynamic deterioration after receiving milk and molasses enemas. One of these
      children died and the others recovered after aggressive resuscitation.
      CONCLUSIONS: Milk and molasses enema administration can be associated with
      significant hemodynamic compromise. These risks appear similar to those risk
      observed with the use of other enema preparations.

PMID- 12500013
TI  - Impact of fortified breakfast cereals on iron intake in German children and
      adolescents.

PMID- 12500014
TI  - Successful pregnancy outcome in tufting enteropathy.

PMID- 12500015
TI  - On a newly proposed in vitro proarrhythmia model.

PMID- 12500016
TI  - Contribution of K+ channels to relaxation induced by 17beta-estradiol but not by
      progesterone in isolated rat mesenteric artery rings.
AB  - 17beta-Estradiol and progesterone were found to relax various vascular beds
      through multiple mechanisms. However, the exact ionic mechanisms underlying the
      acute relaxant responses to both hormones are incompletely understood. This study
      was aimed to examine the possible role of K channel activation in the relaxation
      induced by both hormones in isolated rat mesenteric artery rings. Isometric
      tension of each ring was measured with Grass force displacement transducers. In
      rat endothelium-denuded rings preconstricted by 9,11-dideoxy-11alpha,9alpha-epoxy
      methanoprostaglandin F (U46619), the relaxation induced by 17beta-estradiol was
      partially inhibited by tetrapentylammonium, 4-aminopyridine, iberiotoxin, BaCl,
      and tertiapin-Q but not by tetraethylammonium, charybdotoxin, apamin, or
      glibenclamide. In contrast, these putative K channel blockers, except for
      glibenclamide, did not affect the relaxant response to progesterone. In 4 x 10(
      2) K -preconstricted rings, the K channel blockers lost their inhibitory effects
      on 17beta-estradiol-induced relaxation. Endothelium did not seem to be involved
      in the effects of K channel blockers on 17beta-estradiol-mediated relaxation.
      Nifedipine-induced relaxation was not inhibited but was instead enhanced by
      tetrapentylammonium, iberiotoxin, 4-aminopyridine, and BaCl2. The above results
      indicate that in rat mesenteric artery rings, nonselective activation of K
      channels contributes partially to the relaxation induced by 17beta-estradiol.
      These K channels involved in the estrogen response appeared to be sensitive to
      inhibition by K(Ca), K, and K(IR) channel blockers. Lack of effect of K channel
      blockers on progesterone-induced relaxation suggests that these K channels play
      little or no role. The present findings provide pharmacological evidence for an
      additional mechanism contributing to acute vasorelaxation induced by 17beta
      estradiol.

PMID- 12500017
TI  - Blinded test in isolated female rabbit heart reliably identifies action potential
      duration prolongation and proarrhythmic drugs: importance of triangulation,
      reverse use dependence, and instability.
AB  - Drug-induced proarrhythmia is a rare but potentially lethal adverse drug
      reaction. To test whether the SCREENIT system (an automated computerized test
      apparatus), using an isolated perfused heart obtained from female rabbits, could
      correctly identify agents that lengthen the action potential duration (APD) and
      drugs known to induce proarrhythmia, 14 drugs (penicillin G, haloperidol,
      adriamycin, indapamide, verapamil, aspirin, lidocaine, clomipramine, propranolol,
      erythromycin, quinidine, terfenadine, amiodarone, and thioridazine) were coded
      and submitted for a blinded test. Of these drugs, eight are reported to induce QT
      prolongation in the clinic (adriamycin, clomipramine, quinidine, amiodarone, and
      thioridazine), while three do not lengthen and three shorten the QT. To test for
      reproducibility, four drugs were given in duplicate (haloperidol, aspirin,
      erythromycin, and terfenadine). The drug effects on monophasic APD, conduction,
      instability (index of variability of APD), triangulation (index of duration of
      fast repolarization), and reverse use dependence were measured at five drug
      concentrations (0.05, 0.15, 0.5, 1.5, and 5 mg/l). All 14 blinded drugs, in the
      concentrations used, were correctly identified as to their effects on APD and
      conduction. The drugs eliciting drug-induced proarrhythmia in patients were also
      identified as promoting instability, triangulation, and reverse use dependence in
      the rabbit heart. Importantly, none of the safe agents was labeled as
      proarrhythmic, and the results were very consistent between duplications. In
      conclusion, SCREENIT correctly identifies prolongation of APD, accurately
      separates safe agents form proarrhythmic drugs, and has highly reproducible
      results. Thus, the isolated perfused rabbit heart can be a valuable tool in a
      preclinical proarrhythmia test battery in drug development.

PMID- 12500018
TI  - Electrocardiographic effects of intravenous cocaine: an experimental study in a
      canine model.
AB  - Cocaine abuse causes cardiac dysfunction. Acute intravenous administration of
      cocaine may lead to development of severe arrhythmias, conduction abnormalities,
      ST-T changes, and sudden death. Understanding arrhythmogenesis due to cocaine may
      provide a therapeutic approach to reduce morbidity and mortality. We studied the
      arrhythmogenic activity and other electrocardiographic abnormalities resulting
      from an intravenous bolus of cocaine. Baseline and postanesthetic
      electrocardiographic findings were compared with those after administration of
      intravenous bolus of various doses of cocaine hydrochloride in 20 dogs. The study
      was done in three phases (phase I: low dose of cocaine [1 mg/kg, 15 experiments];
      phase II: medium dose [2 mg/kg, 30 experiments]; and phase III: high dose [5-7
      mg/kg, 10 experiments]). Plasma levels of cocaine were estimated. The low dose
      induced sinus bradycardia, sinus arrhythmia, atrial ectopic, wandering pacemaker,
      unifocal ventricular premature contractions, and ventricular couplets. The medium
      dose generated moderately severe arrhythmias that were of supraventricular
      origin. Atrial flutter and atrial fibrillation were observed in two experiments
      each. Ventricular arrhythmias were manifested as unifocal, multifocal,
      interpolated ventricular premature contractions as well as bigeminy, trigeminy,
      couplets, and salvos. The high dose of 5-7 mg/kg increased electrocardiographic
      intervals and caused ST-segment elevation as well as serious life-threatening
      arrhythmias. Three of the dogs developed sustained ventricular tachycardia
      followed by ventricular flutter-fibrillation and death.

PMID- 12500019
TI  - Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after
      spaceflight.
AB  - Insomnia is a common symptom, not only in the adult population but also in many
      astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an
      imidazopyridine), are often taken to relieve insomnia. Temazepam has been shown
      clinically to have hemodynamic side effects, particularly in the elderly;
      however, the mechanism is not clear. Zolpidem does not cause hemodynamic side
      effects. The purpose of this study was to determine whether the use of different
      hypnotics during spaceflight might contribute significantly to the high incidence
      of postflight orthostatic hypotension, and to compare the findings in astronauts
      with clinical research. Astronauts were separated into three groups: control (n =
      40), temazepam (15 or 30 mg; n = 9), and zolpidem (5 or 10 mg; n = 8). In this
      study, temazepam and zolpidem were only taken the night before landing. The
      systolic and diastolic blood pressures and heart rates of the astronauts were
      measured during stand tests before spaceflight and on landing day. On landing
      day, systolic pressure decreased significantly and heart rate increased
      significantly in the temazepam group, but not in the control group or in the
      zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight
      when astronauts are hemodynamically compromised. Temazepam should not be the
      initial choice as a sleeping aid for astronauts. These results in astronauts may
      help to explain the hemodynamic side effects in the elderly who are also
      compromised. Zolpidem may be a better choice as a sleeping aid in these
      populations.

PMID- 12500020
TI  - Decrease in plasma NOx concentration by isosorbide dinitrate, an organic nitrate
      ester.
AB  - It has been suggested that isosorbide dinitrate (ISDN)-induced venodilation could
      be ascribed to preferential accumulation of the agent in venous tissues,
      resulting in higher concentrations of nitric oxide (NO). Here, the authors
      investigated whether the venodilating effect of ISDN is associated with a
      preferential increase in plasma concentrations of NOx (NO2- and NO3-, stable end
      products of NO) in venous blood than arterial blood. Plasma NOx was measured by
      high-performance liquid chromatography-Griess system with a sensitivity of 0.01
      microM for NO2- and 0.1 microM for NO3-. Arterial and venous blood samples were
      obtained after coronary angiography from the aorta and right atrium of patients
      with or without ischemic heart disease. Nicardipine, a calcium channel blocker,
      was used as a non-NO-related arteriovasodilator. At 1 mg i.v., it did not cause
      any changes in NOx concentration in arterial and venous blood irrespective of
      hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2- and decreased NO3-
      in both arterial and venous blood, with concomitant venodilation. Further
      analysis revealed that plasma NO increased in the pulmonary circulation and this
      increase was preserved after nicardipine and ISDN, and that ISDN, but not
      nicardipine, increased plasma NO3- in the pulmonary circulation. The authors did
      not detect higher concentrations of NOx in venous blood relative to their level
      in arterial blood. Further studies are necessary to clarify the kinetics of NO
      and NO-related compounds in the whole body.

PMID- 12500021
TI  - Combined effects of enalapril and spironolactone in hamsters with dilated
      cardiomyopathy.
AB  - Chronic angiotensin I-converting enzyme inhibition can be associated with
      aldosterone escape. We investigated the effects of enalapril, spironolactone, and
      their combination on hemodynamics and cardiac remodeling in cardiomyopathic
      hamsters to determine whether these drugs could exert additive effects.
      Cardiomyopathic hamsters, Bio TO-2 dilated strain, were orally treated with
      enalapril (20 mg. kg. day ) and/or spironolactone (20 mg. kg. day ) according to
      a 2 x 2 factorial design from 120 days of age. Animals were investigated at 180
      (10 animals per group) and 240 (16 animals per group) days of age. Compared with
      corresponding untreated groups, enalapril significantly decreased mean blood
      pressure (-18%); enalapril and spironolactone significantly increased cardiac
      output (+28%, +11%) and femoral blood flow (+10%, +12%) and significantly
      decreased systemic (-38%, -17%) and femoral (-26%, -13%) vascular resistances.
      Enalapril and spironolactone significantly decreased left ventricle cavity area (
      21%, -26%) and left (-34%, -47%) and right (-37%, -48%) ventricle collagen
      density. Spironolactone significantly increased left ventricle wall thickness
      (+4%). There were significant enalapril x spironolactone interactions for most
      variables (compared with control group, +52%, +36%, +45% for cardiac output;
      +26%, +28%, +26% for femoral blood flow; -50%, -30%, -45% for systemic vascular
      resistance; -33%, -20%, -35% for femoral vascular resistance; -27%, -31%, -40%
      for left ventricle cavity area; and -46%, -58%, -60% for left and -39%, -50%, 
      66% for right ventricle collagen density in enalapril, spironolactone, and
      enalapril + spironolactone groups, respectively). In cardiomyopathic hamsters,
      enalapril and spironolactone in combination did not improve hemodynamics more
      than enalapril alone but induced stronger effects than each drug alone on cardiac
      remodeling.

PMID- 12500022
TI  - Comparison of micronized fenofibrate and pravastatin in patients with primary
      hyperlipidemia.
AB  - Micronized fenofibrate lowers total cholesterol and low-density lipoprotein
      cholesterol to a similar extent as statins but raises high-density lipoprotein
      cholesterol and lowers triglycerides to a greater extent. The comparative lipid
      modifying efficacy of micronized fenofibrate and pravastatin has not been
      evaluated in dyslipidemic patients. This prospective, multicenter, randomized
      trial compared the efficacy of 3 months' treatment with micronized fenofibrate
      (200 mg once daily) or pravastatin (20 mg once daily) in hypercholesterolemic
      type IIa and mixed dyslipidemic type IIb patients. Two hundred sixty-five male
      and female patients (18-75 years) were recruited from 28 European centers, and
      151 were analyzed. Micronized fenofibrate was at least as effective as
      pravastatin in reducing levels of low-density lipoprotein cholesterol and total
      cholesterol in primary dyslipidemia but was significantly more effective than
      pravastatin in raising high-density lipoprotein cholesterol (respectively, 13.2%
      vs. 5.6%; p = 0.0084) and lowering triglycerides (-38.7% vs. -11.8%; p = 0.0001).
      In type IIa dyslipidemia, micronized fenofibrate was as effective as pravastatin
      in raising high-density lipoprotein cholesterol (+8.6% vs. +8.0%) but was
      fivefold more effective in lowering triglycerides (-34.3% vs. -7.2%; p = 0.0001).
      In type IIb dyslipidemic patients with low baseline high-density lipoprotein
      cholesterol levels, micronized fenofibrate was 10-fold and nearly 3-fold superior
      to pravastatin in raising high-density lipoprotein cholesterol and lowering
      triglycerides, respectively. Micronized fenofibrate may be considered an
      effective first-line therapy for patients with primary hyperlipidemia,
      particularly those with type IIb mixed dyslipidemia or type 2 diabetes.

PMID- 12500023
TI  - Role of central and sympathetic nervous systems in pressor effect of L-NAME.
AB  - The pressor effect of N -nitric-l-arginine methyl ester (l-NAME) in rats has been
      attributed to the inhibition of the endothelial nitric oxide synthase; however,
      recent findings suggest that the central and sympathetic nervous systems may be
      also involved. In the present work, the authors attempted to study the possible
      central and sympathetic mechanisms involved in the pressor effect of l-NAME. They
      compared mean arterial pressure response during 1 h of continuous infusion of
      normal saline or l-NAME (0.031 mg. kg. min ) in Wistar rats treated with
      reserpine, adrenal medullectomy, pithing, and pithing + medullectomy. After 15-20
      min infusion, a significantly greater increase of mean arterial pressure was
      observed in anesthetized rats with l-NAME and l-NAME + medullectomy versus rats
      with l-NAME + reserpine and l-NAME + pithing, and the magnitude of the difference
      increased further during the continuous 1-h l-NAME infusion. Adrenal medullectomy
      totally abolished the pressor effect of l-NAME in pithed group. The present
      findings suggest that the central and sympathetic nervous systems play important
      roles in the maintenance of the pressor effect of l-NAME, while the adrenal
      medulla becomes important only when the sympathetic nervous system has been
      suppressed.

PMID- 12500024
TI  - Adenosine receptor subtypes mediating coronary vasodilation in rat hearts.
AB  - Adenosine receptor-mediated coronary vasodilation was studied in isolated hearts
      from young (1-2 months) and mature (12-18 months) Wistar rats. The nonselective
      agonist 5'-N-ethylcarboxamidoadenosine (NECA) induced biphasic concentration
      dependant dilation with similar potencies in both age groups (p < 0.05). Despite
      similar potencies, responses to NECA were significantly depressed by 50% with
      age. NECA-mediated dilation was unaltered by selective A adenosine receptor
      (A1AR) antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 100 nM ) or A
      adenosine receptor (A2AAR) antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)
      pyrazolo-[4,3-e]-1,2,4-triazolo[1,5- ]pyrimidine (SCH 58261, 100 nM ). However,
      the A2B adenosine receptor (A2B AR) selective antagonist alloxazine (10 microM )
      significantly reduced response magnitude to NECA in both age groups.
      Concentration-response curves to N -2-(4-aminophenyl) ethyladenosine (APNEA)
      induced biphasic concentration-dependent dilation in hearts from young animals.
      In the presence of the three combined antagonists, 1 microM DPCPX, 100 nM SCH
      58261, and 1 microM alloxazine, the response magnitude was significantly
      attenuated (p < 0.05). The addition of the A3 adenosine receptor (A3AR)
      antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethyl-6-phenyl-1,4-(+/-)
      dihydropyridine-3,5-dicarboxylate (MRS1191, 100 nM ) to the combined antagonists
      further attenuated vasodilator responses to APNEA. The results suggest that
      multiple adenosine receptor subtypes mediate dilation in the rat coronary
      circulation. NECA mediates vasodilation via the A2BAR subtype, while dilator
      responses to APNEA in the presence and absence of A1, A2, and A3 ARs antagonists
      provide evidence for a vasodilator role for A3 ARs in rat coronary circulation.
      The magnitude of the coronary dilator response is reduced with age and does not
      involve A2A or A1 ARs.

PMID- 12500025
TI  - Renoprotective effects of chronic candesartan treatment in uninephrectomized rat.
AB  - The authors recently observed an age-dependent reduction in the diuretic and
      natriuretic responses to plasma volume expansion in uninephrectomized control and
      glucose-intolerant rats. To determine the involvement of angiotensin II AT
      receptors in this phenomenon, the authors tested the hypothesis that chronic
      candesartan treatment preserves renal excretory function in the uninephrectomized
      rat. Control and glucose-intolerant rats underwent right nephrectomy at 4 weeks
      of age. Two weeks later, the animals in each group were further subdivided and
      maintained on tap water containing either candesartan cilexetil (10 mg. kg(-1).
      day(-1) ) or vehicle. Renal excretory responses to acute extracellular fluid
      volume expansion (5% of body weight over 30 min) were determined in the 9-month
      old conscious animal. Candesartan treatment markedly reduced the mean arterial
      pressure of controls and glucose-intolerant rats. Nonetheless, the baseline rates
      of fluid and electrolyte excretion, as well as the saline volume-induced
      diuretic, natriuretic, and kaliuretic responses, were greater in the candesartan
      treated rats than in their vehicle-treated counterparts. The augmented baseline
      rates of fluid and sodium excretion in candesartan-treated rats were caused by a
      reduction in tubular reabsorption activity and an increase in glomerular
      filtration rate. However, the candesartan-mediated enhancement in saline volume
      induced diuresis and natriuresis was caused by a reduction in tubular
      reabsorption activity. In addition to improving renal function, candesartan
      treatment reduced proteinuria in both groups. In conclusion, chronic blockade of
      the angiotensin II receptors exerts hypotensive and renoprotective effects in the
      aging uninephrectomized rat.

PMID- 12500026
TI  - Statins regulate alpha2beta1-integrin expression and collagen I-dependent
      functions in human vascular smooth muscle cells.
AB  - HMG-CoA reductase inhibitors have direct vascular effects that contribute to
      plaque stability. In the current study, the authors demonstrate that the HMG-CoA
      reductase inhibitors atorvastatin and pravastatin augment the adhesion of human
      (HSMCs) and rat aortic smooth muscle cells (RASMCs) to collagen I via induction
      of alpha2beta1-integrin receptors. Atorvastatin (0.1 microM ) increased the
      adhesion of HSMCs to collagen I up to 2-fold (p < 0.01) and pravastatin (1.0
      microM ) up to 1.8-fold (p < 0.01) after treatment of at least 24 h. This
      increase in adhesion was concentration dependent and was observed for treatment
      periods from 16 to 72 h. Inhibition of isoprenoid synthesis with mevalonate and
      geranyl-geraniol prevented the statin-induced effect on human and rat smooth
      muscle cells. Flow cytometry revealed an increased expression of alpha2- and
      beta1-integrins after treatment with atorvastatin (0.1 microM ) at 24 and 48 h.
      Atorvastatin increased levels of beta1-integrin mRNA after 12- and 24-h treatment
      in HSMCs, which was inhibited by mevalonate. Furthermore, atorvastatin (0.1
      microM ) and pravastatin (1.0 microM ) inhibited chemotaxis of HSMCs on collagen
      I, which was also reversed by mevalonate treatment. In contrast, inhibition of
      beta1-integrins with a specific antibody nearly doubled (p < 0.01) the rate of
      chemotaxis. These data indicate that the chemotactic activity in HSMCs is
      inhibited in part by up-regulation of alpha2beta1-integrin receptors. The current
      study indicates that HMG-CoA reductase inhibitors increase cell-matrix
      interaction with collagen I via induction of alpha2beta1-integrins and increased
      adhesion to collagen I.

PMID- 12500027
TI  - Importance of creatine kinase activity for functional recovery of myocardium
      after ischemia-reperfusion challenge.
AB  - To define the relation between the phosphoryl transfer via creatine kinase and
      the ability to recover from an ischemia-reperfusion challenge, the authors
      chemically inhibited creatine kinase activity with iodoacetamide (IAm) and then
      measured myocardial recovery after 2, 10, or 30 min of global ischemia followed
      by 30 min of reperfusion in the isolated, arterially perfused interventricular
      septa of the rabbit heart. During normoxia, IAm (0.5 M perfused for 15 min) did
      not by itself modify developed tension, maximal rate of tension development, or
      resting tension. In ischemia, IAm pretreatment increased the rate of developed
      tension loss and highly diminished developed tension recovery after reperfusion
      for all the ischemia periods tested. Moreover, IAm significantly enhanced the
      maximal increase in the resting tension induced by 10 or 30 min of ischemia plus
      reperfusion. Lactate dehydrogenase activity in reperfusion was also significantly
      increased over untreated septa. On the basis of the present results, the authors
      suggest that the aggravating effects exhibited by IAm on the ischemic myocardium
      are compatible with its creatine kinase inhibition properties and that creatine
      kinase activity is essential for full recovery from an ischemia-reperfusion
      challenge.

PMID- 12500028
TI  - Ouabain changes arterial blood pressure and vascular reactivity to phenylephrine
      in L-NAME-induced hypertension.
AB  - Ouabain is an endogenous compound that has been associated with the genesis and
      maintenance of hypertension. This compound inhibits the Na+ pump activity, which
      leads to an accumulation of intracellular Na and ultimately might increase
      vascular tone. In nanomolar concentrations, it enhances vasopressor responses to
      phenylephrine in some vascular beds from normotensive and hypertensive rats.
      However, it is not known whether this action of ouabain is a common mechanism for
      all models of hypertension. The aim of this work was to determine whether ouabain
      can alter pressor responses to phenylephrine in rats with Nomega-nitro-l-arginine
      methyl ester (L-NAME)-induced hypertension. In anesthetized rats, ouabain (0.18
      microg/kg, i.v.) increased arterial blood pressure in L-NAME-treated rats but not
      in controls. Ganglionic blockade by hexamethonium (5 mg/kg, i.v.) prevented the
      increase in arterial blood pressure produced by ouabain in L-NAME-treated rats.
      Additional studies using isolated perfused tail artery preparations were
      performed to investigate which factors are involved in the action of ouabain in L
      NAME-treated rats. The effects of 10 nM ouabain on the vasoconstrictor actions of
      phenylephrine were determined on preparations with intact or damaged endothelium
      or in the presence of tetraethylammonium (a K+-channel blocker). Ouabain reduced
      pressor actions of phenylephrine in preparations with an intact endothelium.
      However, after endothelial damage or infusing tetraethylammonium, the response to
      phenylephrine was increased after ouabain. In tails from L-NAME-treated rats, the
      functional activity of the Na, K+-ATPase was reduced, and 10 nM ouabain did not
      produce any further reduction. In conclusion, in this model of hypertension, a
      low dose of ouabain (0.18 microg/kg) increased arterial blood pressure in vivo
      probably as a result of increased sympathetic tone. However, this effect was not
      accompanied by an enhanced action of phenylephrine on the tail vascular bed with
      an intact endothelium. The results suggest that this was due to the release of an
      endothelium-derived K+-channel opener.

PMID- 12500029
TI  - ETA, mixed ETA/ETB receptor antagonists, and protein kinase C inhibitor prevent
      acute hypoxic pulmonary vasoconstriction: influence of potassium channels.
AB  - The aims of this study were to investigate the effects of a selective ETA (BQ
      123), a selective ETB (BQ-788), and a specific mixed ETA/ETB receptor antagonist
      (bosentan) on the pulmonary vasoconstriction induced by hypoxia in the isolated
      perfused rat lung, and the role of nitric oxide, adenosine triphosphate-sensitive
      (KATP), large conductance Ca+-activated (BKCa) and 4-aminopyridine-sensitive
      voltage-gated K channels (K+) in the relaxant effects of the selective ETA
      receptor antagonist BQ-123 and a protein kinase C inhibitor, bisindolylmaleimide
      I. K+ channels were inhibited by glibenclamide, charybdotoxin, and 4
      aminopyridine and nitric oxide synthase by L-NG-nitroarginine methyl ester (L
      NAME). Hypoxic ventilation produced a significant pressure response (+57%, p <
      0.001). BQ-123, bosentan, and bisindolylmaleimide I induced a concentration
      dependent decrease of the hypoxic pressure response (p < 0.001), whereas BQ-788
      did not exhibit any inhibitory effect against hypoxic pressure response.
      Glibenclamide, charybdotoxin, and 4-aminopyridine partially opposed the
      inhibitory effects elicited by BQ-123 (p < 0.05), but L-NAME did not modify these
      effects. The effects of bisindolylmaleimide I on hypoxic pressure response were
      unaffected by glibenclamide, charybdotoxin, or 4-aminopyridine. The authors
      conclude that (a) ETA receptors and protein kinase C are involved in the
      modulation of hypoxic pulmonary vasoconstriction; and (b) the ETA antagonist BQ
      123 opposes hypoxic pulmonary vasoconstriction through KATP, KV, and BKCa
      channels, differing in this from the protein kinase C inhibitor
      bisindolylmaleimide I. These results suggest that BQ-123 operates through a
      mechanism independent of bisindolylmaleimide I-inhibited protein kinase C
      isoforms.

PMID- 12500030
TI  - Pressor response to intravenous tyramine is a marker of cardiac, but not
      vascular, adrenergic function.
AB  - Intravenous injections of the indirect sympathetic amine, tyramine, are used as a
      test of peripheral adrenergic function. The authors measured the time course of
      increases in ejection fraction, heart rate, systolic and diastolic pressure,
      popliteal artery flow, and greater saphenous vein diameter before and after an
      injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects.
      The tyramine caused moderate, significant increases in systolic pressure and
      significant decreases in total peripheral resistance. The earliest changes were a
      30% increase in ejection fraction and a 16% increase in systolic pressure,
      followed by a 60% increase in popliteal artery flow and a later 11% increase in
      greater saphenous vein diameter. There were no changes in diastolic pressure or
      heart rate. These results suggest that pressor responses during tyramine
      injections are primarily due to an inotropic response that increases cardiac
      output and pressure and causes a reflex decrease in vascular resistance. Thus,
      tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic
      function.

PMID- 12500031
TI  - Selective A2A adenosine receptor agonist as a coronary vasodilator in conscious
      dogs: potential for use in myocardial perfusion imaging.
AB  - The authors sought to demonstrate the advantages of a selective, potent, short
      acting A adenosine receptor agonist, CVT-3146 (2-(N-pyrazolyl)Ado derivative),
      for potential clinical use as a coronary vasodilator during myocardial perfusion
      imaging. The use of adenosine in a pharmacological stress test during myocardial
      imaging is limited by side effects mediated by A1 and A2B adenosine receptors and
      by its ultrashort duration of action. CVT-3146 (0.1-5 microg/kg) and adenosine
      (13-267 microg/kg) were given as peripheral intravenous injections in 10 awake
      dogs instrumented for measurement of coronary blood flow (CBF). CVT-3146 caused a
      dose-dependent increase of CBF (ED50 = 0.34 +/- 0.08 microg/kg, maximal increase
      = 221 +/- 18%, n = 6). Adenosine was less potent (ED = 51 +/- 15 microg/kg, p <
      0.05) but equieffective (maximal increase in CBF = 227 +/- 11%). The increase in
      CBF caused by 2.5 microg/kg CVT-3146 reached 84 +/- 5% of the maximal reactive
      hyperemia following 20 s of coronary occlusion (n = 4). After a 10-s injection of
      CVT-3146 (2.5 microg/kg), the increase in CBF remained at least twofold above
      baseline for 97 +/- 14 s, whereas for adenosine (267 microg/kg), the twofold
      increase in CBF lasted only 24 +/- 2 s (p < 0.01, n = 6). A 30-s injection of 2.5
      microg/kg CVT-3146 prolonged the twofold increase in CBF up to 221 +/- 20 s. No
      atrioventricular block was noted. At 2.5 microg/kg, the peak effect of CVT-3146
      on CBF was associated with a short-lasting (20 +/- 6 s) increase in heart rate
      (78 +/- 9 bpm) and decrease in mean arterial blood pressure (13 +/- 6 mm Hg, p <
      0.05, n = 6). CVT-3146 is a potent coronary vasodilator. Its short duration of
      action, minimal and transient systemic hemodynamic effects, and ease of
      administration may make this agonist suitable for pharmacological coronary
      vasodilation during myocardial perfusion imaging for noninvasive detection of
      subcritical arterial stenosis.

PMID- 12500032
TI  - HMR 1556, a potent and selective blocker of slowly activating delayed rectifier
      potassium current.
AB  - The slowly activating delayed rectifier potassium current (IKs) contributes
      prominently to ventricular repolarization of the cardiac action potential.
      Development of a selective IKs blocker is important for the elucidation of the
      physiologic and pathophysiologic relevance of IKs and the development of
      antiarrhythmic strategies. HMR 1556 [(3R,4S)-(+)-N-[3-hydroxy-2,2-dimethyl-6
      (4,4,4-trifluorobutoxy) chroman-4-yl]-N-methylmethanesulfonamide] is a new
      chromanol derivative developed as a selective IKs blocker. Chromanol 293B, the
      most specific IKs blocker currently available, also inhibits the transient
      outward current (Ito). HMR 1556 was examined for its effects on IKs compared with
      rapidly activating delayed rectifier (IKr), inward rectifier (IK1), Ito, and L
      type calcium (ICa.L) currents in canine left ventricular myocytes. HMR 1556 (0.5
      500 nM ) inhibited IKs in a concentration-dependent manner (IC50 of 10.5 nM,
      compared with chromanol 293B's IC50 of 1.8microM). Inhibition of Ito was observed
      only at relatively high concentrations (IC50 of 33.9 microM comparable to
      chromanol 293B's IC of 38 microM). High concentrations of HMR 1556 also inhibited
      ICa.L (IC of 27.5 microM) and IKr (IC50 of 12.6 microM) while IK1 was unaffected.
      Our results indicate that HMR 1556 is superior to chromanol 293B in its potency
      and specificity for inhibition of IKs, making it a valuable experimental tool and
      a potential therapeutic agent.

PMID- 12500034
TI  - Epidemiology and randomized clinical trials.

PMID- 12500035
TI  - Hormone replacement therapy in epidemiologic studies and randomized clinical
      trials - are we checkmate?

PMID- 12500036
TI  - Larger lessons from the Women's Health Initiative.

PMID- 12500037
TI  - Observational studies and randomized trials of hormone replacement therapy: what
      can we learn from them?

PMID- 12500038
TI  - New problems for an old design: time series analyses of air pollution and health.

PMID- 12500039
TI  - Time series analyses of air pollution and health: straining at gnats and
      swallowing camels?

PMID- 12500040
TI  - Health effects of electric and magnetic fields: are we done yet?

PMID- 12500041
TI  - The effect of concurvity in generalized additive models linking mortality to
      ambient particulate matter.
AB  - In recent years, a number of studies have applied generalized additive models to
      time series data to estimate associations between exposure to air pollution and
      cardiorespiratory morbidity and mortality. If concurvity, the nonparametric
      analogue of multicollinearity, is present in the data, statistical software such
      as S-plus can seriously underestimate the variance of fitted model parameters,
      leading to significance tests with inflated type 1 error. This paper uses
      computer simulation and analyses of actual epidemiologic data to explore this
      underestimation of standard errors. We provide a method for assessing concurvity
      in data and an alternate class of models that is unaffected by concurvity. We
      argue that some degree of concurvity is likely to be present in all epidemiologic
      time series datasets and we explore through the use of meta-analysis the possible
      impact of concurvity on the existing body of work relating ambient levels of
      sulfate particles to mortality.

PMID- 12500042
TI  - Smoking, blood pressure and serum cholesterol-effects on 20-year mortality.
AB  - BACKGROUND: To study the impact of smoking and blood pressure conditional on
      serum total cholesterol levels, we investigated the 20-year mortality risk
      associated with high systolic blood pressure (> or =140 mmHg) and smoking, at low
      (<5.2 mmol/Liter), medium (5.2-6.49mmol/Liter), and high (> or =6.5 mmol/Liter)
      serum total cholesterol levels. METHODS: The study population comprised a cohort
      of 50,000 men and women age 30-54 years, examined between 1974 and 1980, in five
      Dutch towns. The duration of follow-up averaged 20 years. Age-adjusted relative
      risks (RRs) for mortality from coronary heart disease (CHD), cardiovascular
      diseases (CVD) and all causes were estimated, for six risk profiles (based on
      levels of total cholesterol, systolic blood pressure and smoking), using Cox
      proportional hazards analysis. RESULTS: Given a low cholesterol level, smoking
      had a larger impact than elevated blood pressure on CHD, CVD and all-cause
      mortality. The combination of elevated blood pressure and smoking among persons
      with low cholesterol was associated with RRs of 3.0 for CHD, 6.0 for CVD and 4.1
      for all-cause mortality in men, and 2.3, 3.6 and 2.6, respectively, in women.
      Among persons with high cholesterol, the combination of high blood pressure and
      smoking was associated with RRs of 9.7 for CHD, 13.9 for CVD and 5.7 for all
      cause mortality in men, and 15.9, 9.3 and 4.3, respectively, in women. For each
      risk profile, the absolute number of CHD, CVD and total deaths was larger in men
      than in women. CONCLUSIONS: The results demonstrate the potential power of a
      multifactorial approach to risk factor reduction in the prevention of
      cardiovascular diseases and all-cause mortality.

PMID- 12500043
TI  - The longitudinal association of lead with blood pressure.
AB  - BACKGROUND: Several investigators have reported an association of blood lead or
      bone lead with increased blood pressure and hypertension, but questions remain
      concerning whether these effects are acute or chronic in nature. METHODS: In this
      longitudinal study, we evaluated the relation of lead, measured in blood and
      tibia, to changes in blood pressure between 1994 and 1998. We studied 496 current
      and former employees of a chemical-manufacturing facility in the eastern United
      States who had previous occupational exposure to inorganic and organic lead.
      Cohort members who provided three or four blood pressure measurements during the
      study were included. RESULTS: Mean age at baseline was 55.8 years with a mean of
      18 years since last occupational exposure to lead. Blood lead at baseline
      averaged 4.6 microg/dL (standard deviation [SD] = 2.6) or 0.22 micromole/Liter
      (SD = 0.13). Tibia lead at year three averaged 14.7-microg/gm (SD = 9.4) bone
      mineral. Change in systolic blood pressure during the study was associated with
      lead dose, with an average annual increase of 0.64 mmHg (standard error [SE] =
      0.25), 0.73 mmHg (SE = 0.26), and 0.61 mmHg (SE = 0.27) for every standard
      deviation increase in blood lead at baseline, tibia lead at year three, or peak
      past tibia lead, respectively. CONCLUSIONS: The results support an etiologic role
      for lead in the elevation of systolic blood pressure among adult males and are
      consistent with both acute and chronic modes of action.

PMID- 12500044
TI  - Synthetic bedding and wheeze in childhood.
AB  - BACKGROUND: The reasons for the increase in childhood asthma over time are
      unclear. The indoor environment is of particular concern. An adverse role for
      synthetic bedding on asthma development in childhood has been suggested by cross
      sectional studies that have found an association between synthetic pillow use and
      childhood wheeze. Prospective data on infant bedding have not been available.
      METHODS: Bedding data at 1 month of age were available from an infant survey for
      children who were participating in a 1995 follow-up study (N = 863; 78% traced).
      The 1995 follow-up was embedded in a larger cross-sectional survey involving
      6,378 seven year olds in Tasmania (N = 92% of eligible). Outcome measures
      included respiratory symptoms as defined in the International Study of Asthma and
      Allergies in Childhood protocol. Frequent wheeze was defined as more than 12
      wheeze episodes over the past year compared with no wheeze. RESULTS: Synthetic
      pillow use at 1 month of age was associated with frequent wheeze at age 7
      (adjusted relative risk [aRR] = 2.5; 95% confidence interval [CI] = 1.2-5.5)
      independent of childhood exposure. Current synthetic pillow and quilt use was
      strongly associated with frequent wheeze (aRR = 5.2; CI = 1.3-20.6). Substantial
      trends were evident for an association of increasing number of synthetic bedding
      items with frequent wheeze and with increasing wheeze frequency. Among children
      with asthma, the age of onset of asthma occurred earlier if synthetic bedding was
      used in infancy. CONCLUSIONS: In this cohort, synthetic bedding was strongly and
      consistently associated with frequent childhood wheeze. The association did not
      appear to be attributable to bedding choice as part of an asthma management
      strategy.

PMID- 12500045
TI  - Why do Black Americans have a higher risk of pancreatic cancer than White
      Americans?
AB  - BACKGROUND: For several decades, the incidence of pancreatic cancer has been 50%
      to 90% higher among blacks than among whites in the United States. The purpose of
      this study was to identify risk factors that may contribute to this racial
      disparity. METHODS: We conducted a population-based case-control study of
      pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey
      counties from August 1986 through April 1989. In-person interviews were
      exclusively with subjects (526 cases and 2153 population controls), rather than
      with next of kin. RESULTS: The determinants of the higher incidence of pancreatic
      cancer among blacks than among whites differed by sex. Among men, established
      risk factors (, cigarette smoking, long-term diabetes mellitus, family history of
      pancreatic cancer) account for 46% of the disease in blacks and 37% in whites,
      potentially explaining all but 6% of the excess risk among blacks. Among women,
      however, other factors appear to contribute to the racial disparity, notably
      moderate/heavy alcohol consumption (>7 drinks per week) and elevated body mass
      index (above the first quartile). When these less accepted risk factors were
      combined with the established risk factors, 88% of the disease in black women and
      47% in white women were explained, potentially accounting for all of the excess
      risk among blacks in our female study population. CONCLUSIONS: Among men, the
      established risk factors (mainly cigarette smoking and diabetes mellitus) explain
      almost the entire black/white disparity in incidence. Among women, however, other
      factors appear to contribute to the racial disparity, notably moderate/heavy
      alcohol consumption and elevated body mass index. In the absence of these
      factors, pancreatic cancer incidence rates among blacks probably would not exceed
      those among whites of either sex.

PMID- 12500046
TI  - Mortality of cystic fibrosis patients treated with tobramycin solution for
      inhalation.
AB  - BACKGROUND: Tobramycin solution for inhalation (TOBI; TSI) is indicated to treat
      patients with cystic fibrosis who are infected with Pseudomonas aeruginosa.
      Preliminary findings from a randomized trial indicate that patients who received
      TSI had about half the mortality rate of those assigned to placebo. METHODS: We
      used the Cystic Fibrosis Foundation registry data to conduct a retrospective
      cohort study of the risk of death among cystic fibrosis patients in 1999
      according to their use of TSI during 1998. We controlled for age, lung function,
      height and infection with; other factors were not important confounders. RESULTS:
      The crude risk of death among those who received TSI therapy for 4 or more months
      was 3.5 times greater than that among those who received no TSI (90% confidence
      interval = 3.0-4.2). In general, increased TSI use was related to progressive
      increases in the risk of death. Such a relation is expected because TSI is used
      for those who are close to death, resulting in strong confounding by indication.
      After control of the previously mentioned confounders, the estimated risk ratio
      was reduced from 3.5 to 1.2. Unfortunately, it is difficult to remove confounding
      by indication in its entirety. Using a method that estimates the magnitude of
      uncontrolled confounding, we show that the actual relation between TSI and the
      risk of death is likely to be protective, and may well be consistent with the
      results from the randomized trial. CONCLUSIONS: These data illustrate strong
      confounding by indication and the extent to which the interpretation of data can
      rest on assumptions about the data and its residual biases.

PMID- 12500047
TI  - The correlation of fecundability among twins: evidence of a genetic effect on
      fertility?
AB  - BACKGROUND: Numerous rare genetic conditions are known to influence fecundability
      in both males and females. It is less clear to what extent more subtle genetic
      differences influence fecundability on a population level. METHODS: In 1994 a
      population-based survey was conducted among Danish twins born 1953-1982.
      Fecundability was assessed as the waiting time to pregnancy at the first attempt
      to achieve a pregnancy. RESULTS: The reported time to pregnancy for males was
      slightly shorter than for females but there were no sex differences in intrapair
      similarity. We found an intrapair correlation in time to pregnancy for 645
      monozygotic twin pairs (r = 0.22; 95% confidence interval = 0.12 to 0.32), but no
      intrapair correlation for 826 like-sex dizygotic twin pairs (r = 0.00; 95%
      confidence interval = -0.09 to 0.10). CONCLUSIONS: The correlation in time to
      pregnancy for monozygotic twins suggests genetic factors, although similarities
      in reporting behaviors could also be contributing to the correlation. The lack of
      correlation in time to pregnancy for dizygotic twins indicates that possible
      genetic factors of importance for fecundabililty are acting nonadditively. Hence,
      it may prove difficult to identify specific gene variants that influence
      fecundability on a population level if their effects depend on gene-gene
      interactions.

PMID- 12500048
TI  - Growth in early life and its relation to pubertal growth.
AB  - BACKGROUND: The timing and magnitude of pubertal growth in relation to fetal,
      infancy and childhood growth have not been explored. METHODS: We used data from a
      longitudinal growth study of 3650 full-term healthy children who were born in
      Gothenburg, Sweden in 1973-1975. This analysis included 2738 children with height
      and weight measurements available both in early life and during adolescence.
      RESULTS: We found that faster linear growth during infancy and childhood was
      associated with earlier peak height velocity during adolescence. In contrast,
      greater height and body mass index (BMI) at birth were associated with later peak
      height velocity in adolescence. Children with faster linear growth and greater
      BMI in infancy and childhood had less height gain between ages 8 and 18. However,
      greater height and BMI at birth were associated with more height gain between
      ages 8 and 18 after adjusting for height and BMI in childhood. CONCLUSIONS: Both
      length and BMI (at birth, in infancy and during childhood) are associated with
      the timing and magnitude of pubertal growth. Being small at birth is associated
      with early puberty and a reduced height gain during adolescence.

PMID- 12500049
TI  - Deaths due to injuries among employed adults: the effects of socioeconomic class.
AB  - BACKGROUND: Few studies have investigated socioeconomic status (SES) and external
      causes of death (ie, deaths attributable to injuries). These deaths are of
      particular interest because they are potentially preventable and they represent
      the second leading cause of years of life lost under age 75. METHODS: We studied
      261,723 deaths from external causes in 27 states from 1984 to 1997 among employed
      persons age 20-64. Numerator data came from occupation on the death certificate.
      Occupation-specific denominator data came from the U.S. Census. A Nam-Powers SES
      score was assigned to each occupation based on its relative income and education
      in the U.S. Census. RESULTS: After adjusting for age, sex, year and race, SES was
      strongly associated with mortality from all external causes combined for men
      (rate ratios = 2.9, 2.3, 1.5, and 1.0 by ascending SES quartile), and to a lesser
      extent for women (rate ratios = 1.6, 1.0, 1.1, and 1.0). A similar pattern was
      seen for each of the specific external causes (motor vehicle deaths, suicide,
      homicide, injuries other than by motor vehicle, and medical complications).
      CONCLUSIONS: We estimate 41% of deaths from external causes are attributable to
      having a SES below the top quartile (both sexes combined).

PMID- 12500050
TI  - The design of prophylactic trials for HIV: the case of microbicides.

PMID- 12500052
TI  - Ethnic differences in breast cancer risk: a possible role for pregnancy levels of
      alpha-fetoprotein?
AB  - BACKGROUND: Breast cancer incidence rates are up to five times higher in white
      women in the United States compared with Asian women in China and Japan. A search
      for factors that modify estrogen's biological effect differentially between
      ethnic groups may add to the understanding of international variations in breast
      cancer risk. Recent evidence indicates that alpha-fetoprotein, a glycoprotein
      produced by the fetal liver, has important antiestrogenic properties. During
      pregnancy, alpha-fetoprotein reaches peak concentrations in maternal serum during
      the third trimester. METHODS: We compared pregnancy levels of alpha-fetoprotein
      in a population with high risk of breast cancer (Boston, MA) and low risk
      (Shanghai, China). Blood samples were collected around the 16th week and around
      the 27th week of gestation among women enrolled from March 1994 to October 1995.
      The number of specimens available for alpha-fetoprotein analysis was 1,033.
      RESULTS: Alpha-fetoprotein levels, adjusted for gestational length, were
      substantially higher in Shanghai compared with Boston women at both time points.
      When adjustments were made for prepregnancy weight, parity, offspring's sex and
      maternal age, alpha-fetoprotein levels remained 13% higher in Shanghai at 16
      weeks of pregnancy but not at 27 weeks. CONCLUSIONS: These findings may explain,
      at least in part, the difference in breast cancer risk between Chinese and
      American women. On the population level, alpha-fetoprotein may influence risk by
      modifying the effect of biologically active estrogens both in the mother and in
      female offspring.

PMID- 12500053
TI  - Smallpox eradication in West and Central Africa: surveillance-containment or herd
      immunity?

PMID- 12500054
TI  - Perspectives on smallpox eradication.

PMID- 12500055
TI  - Residence near power lines and the risk of birth defects.
AB  - BACKGROUND: There has been some concern that exposure to electromagnetic fields
      may cause birth defects. We studied risks of birth defects by residential
      exposure to 50-Hz magnetic fields from power lines. METHODS: We estimated the
      distance between residence and power lines for 161,844 Norwegian residences, and
      their corresponding magnetic fields in the period 1980 to 1997. Risks of 24
      categories of birth defects were compared across exposure levels, adjusting for
      social and demographic variables. RESULTS: Among those living near power lines,
      the greatest reductions in risk were for cardiac defects (odds ratio = 0.5; 95%
      confidence interval = 0.3-0.9) and respiratory defects (0.4; 0.2-0.9). The
      largest increase in risk was for esophageal defects (2.5; 1.0-5.9). Other
      associations were weaker and had wide confidence intervals. CONCLUSIONS: There
      was little evidence that residence near power lines affected the risk of birth
      defects. The observed decreased risks of cardiac and respiratory defects and the
      increased risk of esophageal defects should be interpreted with caution given the
      number of endpoints, the imprecision in the calculations of the distance from the
      residence to the power line, and the limited information on pregnant women's
      change of residence.

PMID- 12500056
TI  - The incidence of varicella: correction of a common error.
AB  - BACKGROUND: Interest in the incidence of varicella (chickenpox) has increased
      since the discovery of an effective vaccine, but calculations to date have
      incorrectedly ignored the question of susceptibility. METHODS: We studied the
      occurrence of varicella in Italy on the basis of 33,343 children (age 0-14 years)
      cared for by 35 pediatricians between 1 October 1997 and 30 September 1998. The
      life-table technique was used to calculate the number of susceptible children. On
      this basis, we estimated the corrected age-specific and cumulative incidence.
      RESULTS: We identified 1749 cases among the estimated 21,783 susceptible
      children, for a crude incidence of 8.0% (95% confidence interval [CI] = 7.7-8.4).
      The rate age-standardized to the Italian population 0-14 years old was 6.8 (CI =
      6.5-7.2). The incidence was more than 16% among children age 3-4 years and more
      than 4% for those age 1-10 years. Comparison of the usual method and our
      corrected method showed that the uncorrected method underestimates the crude
      annual incidence (5.2% 8.0%), shifts the peak incidence to earlier ages, and
      underestimates cumulative incidence (at age 14, 49% 67%). CONCLUSIONS: The use of
      our corrected method provides more valid estimates of the incidence of varicella
      than the ones that are currently available. Corrected estimates should be
      preferred to uncorrected ones in models to study the cost-effectiveness of
      universal vaccination against varicella.

PMID- 12500057
TI  - Inflammatory proteins and depression in the elderly.
AB  - BACKGROUND: Clinical studies suggest that depression may be accompanied by an
      activation of the inflammatory response system. We investigated the relation of
      cytokine interleukin-6 and the acute phase proteins alpha1-antichymotrypsin and C
      reactive protein with depression in a population-based study. METHODS: We
      screened for depressive symptoms 3884 adults at age 60 and older living in a
      district of Rotterdam, and performed a psychiatric work-up on those who were
      screened positive. All subjects had blood drawn. We compared levels of
      inflammation markers adjusted for smoking, stroke, functional disability and
      cognitive score for 263 cases with depressive symptoms (including 106 subjects
      with depressive disorders) and 461 randomly selected reference subjects. RESULTS:
      Age- and gender-adjusted analyses suggested associations of alpha1
      antichymotrypsin and C-reactive protein with depressive disorders, but these
      associations disappeared after adjustment for additional confounding factors.
      Even after adjustment, increased levels of interleukin-6 were related to
      depressive disorders (odds ratio per standard deviation increase in interleukin-6
      = 1.47; 95% confidence interval = 1.15-1.89). Further analyses demonstrated that
      this relation was mainly attributable to the subjects with high interleukin-6
      concentrations, suggesting a threshold effect. CONCLUSIONS: Interleukin-6 levels
      were strongly increased in some subjects with depressive disorders, possibly
      indicating a specific immunologic process. However, the associations of acute
      phase proteins with depression in this population-based study could be explained
      by confounding.

PMID- 12500058
TI  - On the expected number of cancer deaths during follow-up of an initially cancer
      free cohort.
AB  - A comparison of expected number of deaths with the observed is a widely used
      method with an extensive history. Epidemiologists often study the mortality rate
      from a particular cancer in an initially healthy population. Using cause-specific
      mortality rates from a reference population will overestimate the expected number
      of deaths because it does not take into account the fact that the study cohort is
      initially cancer free. It is more accurate to calculate the expected number of
      deaths by explicitly considering the probability of getting cancer in a given
      year and the probability of dying from it before the end of the follow-up.

PMID- 12500059
TI  - The slavery hypertension hypothesis: dissemination and appeal of a modern race
      theory.

PMID- 12500060
TI  - The slavery hypothesis of hypertension among African-Americans.

PMID- 12500061
TI  - Salt, slavery and survival- hypertension in the African diaspora.

PMID- 12500062
TI  - Not guilty by reason of doubt?

PMID- 12500064
TI  - Seasonal variation of atrial fibrillation: further supportive evidence.

PMID- 12500065
TI  - Breastfeeding after reduction mammaplasty and augmentation mammaplasty.

PMID- 12500066
TI  - Biologically based study of magnetic field exposure and female breast cancer-
      will there be a sensible interpretation without information on a likely culprit?

PMID- 12500067
TI  - Valproic acid and risperidone: a drug interaction?

PMID- 12500068
TI  - Valproic Acid and risperidone.

PMID- 12500069
TI  - Psychopathology in the parents of boys with gender identity disorder.

PMID- 12500070
TI  - Ziprasidone-associated galactorrhea in a female teenager.

PMID- 12500071
TI  - Recall of childhood psychopathology more than 10 years later.
AB  - OBJECTIVE: This study investigated recall in a sample of depressed, anxious, and
      normal children followed up as adults. Strengths of this study were that the
      length of the retest interval was substantial, follow-up information was
      collected by blind interviewers, and childhood diagnoses were clearly documented.
      METHOD: The sample consisted of 144 subjects with a childhood diagnosis of
      depression, 48 with a childhood diagnosis of anxiety, and 128 normal controls.
      Best-estimate diagnoses assigned at follow-up were compared with childhood
      primary diagnoses. RESULTS: Reliability and sensitivity were fair for major
      depressive disorder (mean = 0.46 and 50%, respectively) and any depression (mean
      = 0.57 and 65%, respectively). Reliability and sensitivity were relatively lower
      for anxiety (mean = 0.32 and 43%, respectively). Sensitivity for any diagnosis
      was good (mean = 71%). Specificity was good among all diagnostic categories
      (range = 73%-100%). Results suggest better diagnostic recall for females than for
      males. Recall was slightly better for subjects who were older than age 12 during
      their original episode. Age-of-onset reliability was poor (major depressive
      disorder = 0.22, any depression = 0.22, and any anxiety = -0.13). CONCLUSIONS:
      Recall of any childhood disorder is moderately reliable and accurate. Recall of a
      specific disorder is less accurate. Depression was more likely to be recalled
      than anxiety. High specificity suggests that participants were not biased to
      report disorders not present in childhood.

PMID- 12500072
TI  - Searching for moderators and mediators of pharmacological treatment effects in
      children and adolescents with anxiety disorders.
AB  - OBJECTIVE: To examine whether age, gender, ethnicity, type of anxiety disorder,
      severity of illness, comorbidity, intellectual level, family income, or parental
      education may function as moderators and whether treatment adherence, medication
      dose, adverse events, or blinded rater's guess of treatment assignment may
      function as mediators of pharmacological treatment effect in children and
      adolescents with anxiety disorders. METHOD: The database of a recently reported
      double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed.
      With a mixed-model random-effects regression analysis of the Pediatric Anxiety
      Rating Scale total score, moderators and mediators were searched by testing for a
      three-way interaction (strata by treatment by time). A two-way interaction
      (strata by time) identified predictors of treatment outcome. RESULTS: No
      significant moderators of efficacy were identified, except for lower baseline
      depression scores, based on parent's (but not child's) report, being associated
      with greater improvement (p < .001). Patients with social phobia (p < .05) and
      greater severity of illness (p < .001) were less likely to improve, independently
      of treatment assignment. Blinded rater's guess of treatment assignment acted as a
      possible mediator (p < .001), but improvement was attributed to fluvoxamine,
      regardless of actual treatment assignment. Treatment adherence tended to be
      associated (p = .05) with improvement. CONCLUSIONS: In this exploratory study,
      patient demographics, illness characteristics, family income, and parental
      education did not function as moderators of treatment effect. Social phobia and
      severity of illness predicted less favorable outcome. Attribution analyses
      indicated that study blindness remained intact. The presence of concomitant
      depressive symptoms deserves attention in future treatment studies of anxious
      children.

PMID- 12500073
TI  - Paroxetine versus clomipramine in adolescents with severe major depression: a
      double-blind, randomized, multicenter trial.
AB  - OBJECTIVE: To date, two randomized, double-blind trials of serotonin reuptake
      inhibitors (SRIs) have shown that antidepressant drugs are effective in treating
      adolescent depression. In contrast, tricyclic antidepressants (TCAs) are not
      superior to placebo. This has led to a serotonin hypothesis in this age group.
      This study explores this hypothesis and compares paroxetine, a specific SRI, with
      clomipramine, a TCA with SRI activity. METHOD: One hundred twenty-one adolescents
      (aged 12-20 years) with major depression were enrolled and randomized (stratified
      for age) to 20 or 40 mg of paroxetine or 75 mg or 150 mg of clomipramine for 8
      weeks. Primary outcome measurements were the Clinical Global Impression (CGI)
      scale and the Montgomery and Asberg Depression Rating Scale (MADRS). RESULTS: Of
      the 121 patients, 58 received clomipramine and 63 paroxetine. Based on intent-to
      treat analysis, both agents had similar efficacy, with no effect of age; 48.3%
      and 58.2% of the subjects receiving clomipramine and 65.1% and 59.3% of those
      receiving paroxetine were rated responders on the MADRS and CGI scales,
      respectively. Study withdrawals were frequent in both groups (41% and 31%,
      respectively), but side effects were significantly more frequent with
      clomipramine (69% versus 49.2%, respectively; p = .027). CONCLUSION: Paroxetine
      and clomipramine exhibit similar efficacy in adolescent depression. These data
      support the serotonin hypothesis but do not confirm it in the absence of a
      placebo arm. Given the adverse event profile of clomipramine, specific SRIs
      should be preferred. However, more placebo-controlled studies are needed to
      establish definitively the efficacy of SRIs in this age group.

PMID- 12500074
TI  - Multiple informant agreement and the anxiety disorders interview schedule for
      parents and children.
AB  - OBJECTIVE: To examine concordance of child, parent, and consensus agreement on
      the Anxiety Disorders Interview Schedule, Child and Parent versions (ADIS-C/P),
      for an outpatient sample of children and adolescents and to explore moderators of
      those relations. Child characteristics (age, gender, social desirability), a
      family environment variable (conflict), and type of diagnoses (internalizing,
      externalizing) were systematically examined. METHOD: These relations were
      examined in 165 children and adolescents referred to a psychological clinic by
      family practitioners, pediatricians, schools, and mental health professionals.
      Participants were individually administered the ADIS-C or ADIS-P by separate
      clinicians, and consensus diagnoses were determined in a clinical conference.
      Agreements between child-parent, child-consensus, and parent-consensus were
      determined. RESULTS: Poor levels of agreement were found among our informants,
      especially between child and parent and to some extent between child and
      consensus. Agreement was higher between parent and consensus, suggesting that our
      clinicians tended to favor parent input over child input. Although the effects
      were complex, characteristics of the child, family, and type of diagnosis
      moderated or qualified these findings. CONCLUSIONS: Although discrepancies exist
      among our informants, our overall findings suggest important information is
      obtained from each informant and, when combined with certain modifying
      characteristics, may lead to diagnostic and treatment decisions.

PMID- 12500075
TI  - Suicidal behavior and violence in male adolescents: a school-based study.
AB  - OBJECTIVE: To investigate characteristics of suicidal and violent behavior in a
      community school sample of adolescents. METHOD: Self-report questionnaires were
      administered to 794 male students (aged 12-18 years) from Antwerp, Belgium.
      Subjects were classified into four groups: a suicidal-only (n = 40; suicidal
      ideation and/or self-harming behavior), a violent-only (n = 142), a suicidal
      violent (n = 21), and a control group (n = 591). RESULTS: Compared with controls,
      higher levels of internalizing problems, risk-taking behavior (substance use,
      diminished perception of risk, sensation seeking), and aggression were found in
      the comparison groups. The suicidal-violent group had the highest levels of
      depression, somatization, overt and covert aggression, and risk-taking behavior.
      Compared with the suicidal-only group, the violent-only group had less
      depression, anxiety, and covert aggression, but higher levels of overt
      aggression, sensation seeking, diminished perception of risk, and marijuana use.
      CONCLUSIONS: Although adolescent suicidal and violent behavior are both related
      to internalizing problems, aggression, and risk-taking behavior, marked
      differences in severity and nature exist in these relationships. Differentiation
      of suicidal youths based on the presence or absence of violent behavior may add
      to our understanding of suicidal phenomena and may thus have important clinical
      consequences.

PMID- 12500076
TI  - Rates and predictors of aftercare services among formerly hospitalized
      adolescents: a prospective naturalistic study.
AB  - OBJECTIVE: To examine rates and predictors of aftercare use, lengths of service
      use, and predictors of the duration of aftercare service use among 180
      adolescents monitored for up to 8.1 years after discharge from an inpatient
      psychiatry unit. METHOD: Drawing upon the Anderson-Newman model of service use,
      severity of illness, enabling, and predisposing factors assessed during the
      hospitalization were examined as potential predictors of service use. Information
      about outpatient mental health specialty services after hospitalization was
      assessed repeatedly and verified with treatment records. RESULTS: Seventy-three
      percent of adolescents received aftercare within the first month after discharge,
      and 92% eventually received outpatient services. Fifty-seven percent of
      adolescents remained in treatment 6 months after initiation of services.
      Psychiatric comorbidity, prior service use, and presence of a biological parent
      or grandparent in the home were related to initial service use. Psychiatric
      comorbidity and history of repeated suicide attempts were related to longer
      duration, and older age and minority group status were related to shorter
      duration of aftercare service use. CONCLUSIONS: Most adolescents receive
      aftercare services, but there are certain groups that are relatively less likely
      to access or remain in services. Interventions to decrease the barriers to care
      in such groups may be beneficial.

PMID- 12500077
TI  - Acculturation strategies and ethnic identity as predictors of behavior problems
      in arctic minority adolescents.
AB  - OBJECTIVE: To explore the effect of acculturation attitudes and ethnic and
      national identity on behavior problems in arctic minority adolescents in northern
      Norway. METHOD: The Youth Self-Report, the Multigroup Ethnic Identity Measure,
      and acculturation strategies were completed by 581 indigenous Sami and 291 Kven
      high school students in 1994-1995, at age 15-18 years. Response rate was 85%.
      Behavior problems were in addition to ethnic/national identity and acculturation
      attitudes studied in relation to ethnicity, gender, age, socioeconomic status,
      parentage, ethnic language, and ethnic context. RESULTS: Although there were no
      ethnic group differences in behavior problems, the impact of ethnocultural
      predictors differed between ethnocultural and indigenous adolescents.
      Acculturation attitudes were most significant for indigenous adolescents' mental
      health, and identity issues showed the strongest impact on ethnocultural peers.
      The study revealed significant gender differences regarding the influence of
      ethnocultural factors, and contextual variation among Sami adolescents with the
      strongest impact in contexts with low density of Sami people. CONCLUSIONS: The
      significant ethnic group variations emphasize the importance of conducting both
      between- and within-group analysis on the impact of ethnocultural issues on
      behavior problems in minority adolescents.

PMID- 12500078
TI  - Psychological comorbidity and stress reactivity in children and adolescents with
      recurrent abdominal pain and anxiety disorders.
AB  - OBJECTIVE: To compare clinical symptoms, diagnoses, and physiological measures in
      children and adolescents with recurrent abdominal pain (RAP) (n = 14), to a group
      with anxiety disorders (ANX) (n = 14) and a physically and psychiatrically
      healthy control group (HC) (n = 14). METHOD: The cross-sectional study examined
      group differences in clinical symptoms of anxiety, somatic complaints,
      depression, and behavior problems. Physiological measures included heart rate,
      systolic and diastolic blood pressure, and salivary cortisol in response to the
      Trier Social Stress Test for Children (TSST-C). Subjects were between the ages of
      8 and 16 years. RESULTS: RAP and ANX subjects had comparable scores on most
      psychological measures, and their scores were higher (n < .05) than those of the
      HC. The ANX and RAP groups exhibited physiological findings that had more shared
      similarities than either group with the HC group. Few statistically significant
      group differences were noted in physiological measures, yet the pattern of
      findings in blood pressure and cortisol supported the use of the TSST-C and the
      direction of the findings was consistent with expectations. CONCLUSIONS:
      Understanding more about comorbidity between RAP and anxiety could have important
      management implications, with observed congruities between the disorders
      suggesting treatments already demonstrated to be efficacious for pediatric
      anxiety and depression might be applied productively to RAP.

PMID- 12500079
TI  - Behavioral validation, precursors, and concomitants of picky eating in childhood.
AB  - OBJECTIVES: To validate the concept of parent-reported picky eating using
      objective, laboratory-based measures and to identify both child and parental
      precursors and concomitants of picky eating. METHOD: One hundred thirty-five
      infants were monitored from birth to 5.5 years. Behavioral measures of picky
      eating were obtained from standardized feedings at ages 3.5 and 5.5 years in the
      laboratory and at home. Child precursors were measures of infant sucking
      behavior; parental precursors were disinhibition of eating, restrained eating,
      body dissatisfaction, and body mass index. Parentally reported attitudes and
      behaviors thought to be related to pickiness and parental concomitants were taken
      from the Stanford Feeding Questionnaire. Child Temperament was assessed by the
      Children's Behavior Questionnaire. RESULTS: Picky eaters ate fewer foods and were
      especially more likely to avoid vegetables. Picky girls decreased their caloric
      intake between ages 3.5 and 5.5, whereas all other children increased their
      caloric intake. None of the included parental precursors was significantly
      related to pickiness. Picky eaters demonstrated a different sucking pattern with
      fewer sucks per feeding session at weeks 2 and 4. Finally, picky children
      displayed more parent-reported negative affect than nonpicky children.
      CONCLUSIONS: Parentally reported picky eating is associated with a consistent
      pattern of inhibited and selective eating beginning in infancy.

PMID- 12500080
TI  - Working memory and sleep in 6- to 13-year-old schoolchildren.
AB  - OBJECTIVE: To study the associations between sleep quality/quantity and
      performance in auditory/visual working memory tasks of different load levels.
      METHOD: Sixty schoolchildren aged 6 to 13 years from normal school classes
      voluntarily participated. Actigraphy measurement was done during a typical school
      week for 72 consecutive hours. It was timed together with the working memory
      experiments to obtain information on children's sleep during that period. The n
      back task paradigm was used to examine auditory and visual working memory
      functions. RESULTS: Lower sleep efficiency and longer sleep latency were
      associated with a higher percentage of incorrect responses in working memory
      tasks at all memory load levels (partial correlations, controlling for age, all p
      values < .05, except in visual 0-back and auditive 2-back tasks); shorter sleep
      duration was associated with performing tasks at the highest load level only
      (partial correlations, controlling for age,p < .05). Also in general linear
      models (controlling for age, gender, and socioeconomic status), sleep efficiency
      (F = 11.706, p = .050) and latency (F = 3.588, p = .034) were significantly
      associated with the mean incorrect response rate in auditory working memory
      tasks. CONCLUSIONS: Sleep quality and quantity affect performance of working
      memory tasks in school-age children. In children with learning difficulties the
      possibility of underlying sleep problems should be excluded.

PMID- 12500081
TI  - Monozygotic twins discordant for attention-deficit/hyperactivity disorder:
      ascertainment and clinical characteristics.
AB  - OBJECTIVE: Nongenetic factors and phenomenology of attention
      deficit/hyperactivity disorder (ADHD) were examined in monozygotic (MZ) twin
      pairs discordant for ADHD. METHOD: Recruitment included telephone screening (n =
      297 pairs), behavioral ratings obtained from parents and teachers (n = 59 pairs),
      and, finally, in-person assessment (n = 25 pairs; structured classroom
      observation, diagnostic interview, psychoeducational evaluation, birth record
      review, establishment of monozygosity, and anatomic brain imaging). Affected
      twins were further contrasted with previously studied affected singletons.
      RESULTS: Of the 25 MZ twin pairs qualifying for in-person evaluation, only 10
      proved discordant for ADHD. Affected twins were mostly comparable with affected
      singletons on clinical measures, although fathers' self-ratings of childhood ADHD
      status were significantly lower in twins than in singletons. CONCLUSIONS:
      Discordance for ADHD in MZ twins appears to be ascribable to greater
      environmental discordance and decreased familiality. Despite these differences,
      affected twins were phenotypically comparable with affected singletons. Thus MZ
      twins discordant for ADHD, while rare, can inform research on the etiology and
      pathophysiology of this disorder.

PMID- 12500082
TI  - Disruptive behavior in children with Tourette's syndrome: association with ADHD
      comorbidity, tic severity, and functional impairment.
AB  - OBJECTIVE: To examine the association of disruptive behavior with social,
      adaptive, and family functioning in Tourette's syndrome (TS) with and without
      comorbid attention-deficit/hyperactivity disorder (ADHD). METHOD: The sample
      included 207 children (144 boys and 63 girls) between the ages of 7 and 18 years.
      Forty-two children received a diagnosis of TS-only, 52 received a diagnosis of
      ADHD-only, 52 children had TS+ADHD, and there were 61 unaffected control
      children. Best-estimate DSM-IV diagnoses were assigned on the basis of structured
      interviews and clinical ratings. Dependent measures included parent and teacher
      ratings of disruptive behavior, parent ratings of social and family functioning,
      and the Vineland Adaptive Behavior Scales. RESULTS: Children with TS-only did not
      differ from unaffected controls on the parent ratings of aggression and
      delinquent behavior or on the teacher ratings of conduct problems. By contrast,
      children with TS+ADHD were rated significantly above unaffected controls and
      similar to children with ADHD-only on these indices of disruptive behavior.
      Hierarchical regression analyses revealed that aggression and delinquency scores
      added unique contributions to impairment in social and family functioning,
      controlling for age, gender, and diagnostic status. CONCLUSIONS: Comorbid ADHD is
      highly associated with disruptive behavior and functional impairment in children
      with TS. When disruptive behavior problems are present, there is an additional
      burden on children's social and family functioning.

PMID- 12500083
TI  - Brain maturation and subtypes of conduct disorder: interactive effects on p300
      amplitude and topography in male adolescents.
AB  - OBJECTIVE: Adolescents with conduct disorder problems are, on average, at
      increased risk for a variety of unfortunate adult outcomes, including substance
      dependence. This study was designed to identify the neurophysiological correlates
      of different categories of conduct disorder problems as well as the relationship
      between these correlates and the maturational status of the brain. METHOD: The
      subjects were 94 males, aged 14-19 years, recruited from the community. None were
      recruited from treatment or juvenile justice programs. The subjects varied in the
      type and number of conduct problem behaviors exhibited prior to age 15. Groups
      were operationally defined by the relative number (0 versus > or =1) of DSM-IV
      conduct disorder diagnostic criteria within each of four categories: rules
      violations, aggression, deceitfulness/theft, and destructiveness. Age was
      included as an additional grouping factor. P300 electroencephalographic
      potentials were recorded while subjects performed a task in which rare auditory
      stimuli were used to signal a change in stimulus-response mapping during a
      succeeding set of trials. RESULTS: Analyses revealed that boys with a history of
      rules violations failed to exhibit the normal maturational increase in P300
      amplitude found in boys without a history of rules violations. Topographic
      analyses of current source densities suggest that the source of the maturational
      deficit involved P300 generators within the frontal brain. Parietal generators of
      P300 matured normally. CONCLUSIONS: The present results are interpreted as
      reflecting a decrement in frontal brain maturation among boys potentially at risk
      for substance dependence, antisocial personality disorder, or other forms of
      adult psychopathology.

PMID- 12500084
TI  - Genetics of childhood disorders: XLVI. Autism, part 5: genetics of autism.

PMID- 12500086
TI  - Beyond the visible--imaging the human brain with light.
AB  - Optical approaches to investigate cerebral function and metabolism have long been
      applied in invasive studies. From the neuron cultured to the exposed cortex in
      the human during neurosurgical procedures, high spatial resolution can be reached
      and several processes such as membrane potential, cell swelling, metabolism of
      mitochondrial chromophores, and vascular response can be monitored, depending on
      the respective preparation. The authors focus on an extension of optical methods
      to the noninvasive application in the human. Starting with the pioneering work of
      Jobsis 25 years ago, near-infrared spectroscopy (NIRS) has been used to
      investigate functional activation of the human cerebral cortex. Recently, several
      groups have started to use imaging systems that allow the generation of images of
      a larger area of the subject's head and, thereby, the production of maps of
      cortical oxygenation changes. Such images have a much lower spatial resolution
      compared with the invasively obtained optical images. The noninvasive NIRS
      images, however, can be obtained in undemanding set-ups that can be easily
      combined with other functional methods, in particular EEG. Moreover, NIRS is
      applicable to bedside use. The authors briefly review some of the abundant
      literature on intrinsic optical signals and the NIRS imaging studies of the past
      few years. The weaknesses and strengths of the approach are critically discussed.
      The authors conclude that NIRS imaging has two major advantages: it can address
      issues concerning neurovascular coupling in the human adult and can extend
      functional imaging approaches to the investigation of the diseased brain.

PMID- 12500087
TI  - Glutathione peroxidase-1 contributes to the neuroprotection seen in the
      superoxide dismutase-1 transgenic mouse in response to ischemia/reperfusion
      injury.
AB  - The authors hypothesized that glutathione peroxidase-1 (Gpx-1) contributes to the
      neuroprotection seen in the superoxide dismutase-1 transgenic (Sod-1 tg) mouse.
      To investigate this hypothesis, they crossed the Gpx-1 -/- mouse with the Sod-1
      tg and subjected the cross to a mouse model of ischemia/reperfusion. Two hours of
      focal cerebral ischemia followed by 24 hours of reperfusion was induced via
      intraluminal suture. The Sod-1 tg/Gpx-1 -/- cross exhibited no neuroprotection
      when infarct volume was measured; indeed, infarct volume increased in the Sod-1
      tg/Gpx-1 -/- cross compared with the wild-type mouse. Our results suggest that
      Gpx-1 plays an important regulatory role in the protection of neural cells in
      response to ischemia/reperfusion injury.

PMID- 12500088
TI  - Mouse hippocampal organotypic tissue cultures exposed to in vitro "ischemia" show
      selective and delayed CA1 damage that is aggravated by glucose.
AB  - Oxygen and glucose deprivation (OGD) in cell cultures is generally studied in a
      medium, such as artificial cerebrospinal fluid (CSF), with an ion composition
      similar to that of the extracellular fluid of the normal brain (2 to 4 mmol/L K+,
      2 to 3 mmol/L Ca2+; pH 7.4). Because the distribution of ions across cell
      membranes dramatically shifts during ischemia, the authors exposed mouse
      organotypic hippocampal tissue cultures to OGD in a medium, an ischemic
      cerebrospinal fluid, with an ion composition similar to the extracellular fluid
      of the brain during ischemia (70 mmol/L K+, 0.3 mmol/L Ca2+; pH 6.8). In ischemic
      CSF, OGD induced a selective and delayed cell death in the CA1 region, as
      assessed by propidium iodide uptake. Cell death was glutamate receptor dependent
      since blockade of the N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors mitigated cell damage. Hyperglycemia aggravates
      ischemic brain damage whereas glucose in artificial CSF prevents oxygen
      deprivation-induced damage. The authors demonstrate that glucose in ischemic CSF
      significantly exacerbates cell damage after oxygen deprivation. This new model of
      "ischemia" can be useful in future studies of the mechanisms and treatment of
      ischemic cell death, including studies using genetically modified mice.

PMID- 12500089
TI  - Traumatic axonal injury results in biphasic calpain activation and retrograde
      transport impairment in mice.
AB  - Traumatic axonal injury (TAI) is one of the most important pathologies associated
      with closed head injury, and contributes to ensuing morbidity. The authors
      evaluated the potential role of calpains in TAI using a new model of optic nerve
      stretch injury in mice. Male C57BL/6 mice were anesthetized, surgically prepared,
      and subjected to a 2.0-mm optic nerve stretch injury (n = 34) or sham injury (n =
      18). At various intervals up to 2 weeks after injury, optic nerves were examined
      for neurofilament proteins and calpain-mediated spectrin breakdown products using
      immunohistochemistry. In addition, fluorescent tracer was injected into the
      superior colliculi of mice 1 day before they were killed, to investigate the
      integrity of retrograde axonal transport to the retina. Optic nerve stretch
      injury resulted in persistent disruption of retrograde axonal transport by day 1,
      progressive accumulation and dephosphorylation of neurofilament protein in
      swollen and disconnected axons, and subsequent loss of neurofilament protein in
      degenerating axons at day 14. Calpains were transiently activated in intact axons
      in the first minutes to hours after stretch injury. A second stage of calpain
      mediated proteolysis was observed at 4 days in axonal swellings, bulbs, and
      fragments. These data suggest that early calpain activation may contribute to
      progressive intraaxonal structural damage, whereas delayed calpain activation may
      be associated with axonal degeneration.

PMID- 12500090
TI  - Cortical spreading depression causes a long-lasting decrease in cerebral blood
      flow and induces tolerance to permanent focal ischemia in rat brain.
AB  - Cortical spreading depression (CSD) has previously been shown to induce tolerance
      to a subsequent episode of transient cerebral ischemia. The objective of the
      present study was to determine whether CSD also induces tolerance to permanent
      focal ischemia and, if so, whether tolerance may be mediated by alterations in
      cerebral blood flow (CBF). Sprague-Dawley rats were preconditioned by applying
      potassium chloride to one hemisphere for 2 hours, evoking 19 +/- 5 episodes of
      CSD (mean +/- SD, n = 19). Three days later, the middle cerebral artery (MCA) was
      permanently occluded using an intraluminal suture. In a subset of animals, laser
      Doppler blood flow (LDF) was monitored over the parietal cortex before and during
      the first 2 hours of MCA occlusion. Preconditioning with CSD reduced the
      hemispheric volume of infarction from 248 +/- 115 mm3 (n = 18) in sham
      conditioned animals to 161 +/- 81 mm3 (n = 19, P< 0.02). Similarly, CSD reduced
      the neocortical volume of infarction from 126 +/- 82 mm3 to 60 +/- 61 mm3 (P <
      0.01). Moreover, preconditioning with CSD significantly improved LDF during MCA
      occlusion from 21% +/- 7% (n = 9) of preischemic baseline in sham-conditioned
      animals to 29% +/- 9% (n = 7, P< 0.02). Preconditioning with CSD therefore
      preserved relative levels of CBF during focal ischemia and reduced the extent of
      infarction resulting from permanent MCA occlusion. To determine whether CSD may
      have altered preischemic baseline CBF, [14 C]iodoantipyrine was used in
      additional animals to measure CBF 3 days after CSD conditioning or sham
      conditioning. CSD, but not sham conditioning, significantly reduced baseline CBF
      in the ipsilateral neocortex to values 67% to 75% of those in the contralateral
      cortex. Therefore, CSD causes a long-lasting decrease in baseline CBF that is
      most likely related to a reduction in metabolic rate. A reduction in the rate of
      metabolism may contribute to the induction of tolerance to ischemia after
      preconditioning with CSD.

PMID- 12500091
TI  - Increased S-nitrosothiols and S-nitrosoalbumin in cerebrospinal fluid after
      severe traumatic brain injury in infants and children: indirect association with
      intracranial pressure.
AB  - Nitric oxide (NO) is implicated in both secondary damage and recovery after
      traumatic brain injury (TBI). Transfer of NO groups to cysteine sulfhydryls on
      proteins produces S-nitrosothiols (RSNO). S-nitrosothiols may be neuroprotective
      after TBI by nitrosylation of N-methyl-D-aspartate receptor and caspases. S
      nitrosothiols release NO on decomposition for which endogenous reductants (i.e.,
      ascorbate) are essential, and ascorbate is depleted in cerebrospinal fluid (CSF)
      after pediatric TBI. This study examined the presence and decomposition of RSNO
      in CSF and the association between CSF RSNO level and physiologic parameters
      after severe TBI. Cerebrospinal fluid samples (n = 72) were obtained from 18
      infants and children on days 1 to 3 after severe TBI (Glasgow Coma Scale score <
      8) and 18 controls. Cerebrospinal fluid RSNO levels assessed by fluorometric
      assay peaked on day 3 versus control (1.42 +/- 0.11 micromol/L vs. 0.86 +/- 0.04,
      P< 0.05). S-nitrosoalbumin levels were also higher after TBI (n = 8, 0.99 +/-
      0.09 micromol/L on day 3 vs. n = 6, 0.42 +/- 0.02 in controls, P< 0.05). S
      nitrosoalbumin decomposition was decreased after TBI. Multivariate analysis
      showed an inverse relation between CSF RSNO and intracranial pressure and a
      direct relation with barbiturate treatment. Using a novel assay, the presence of
      RSNO and S-nitrosoalbumin in human CSF, an approximately 1.7-fold increase after
      TBI, and an association with low intracranial pressure are reported, supporting a
      possible neuroprotective role for RSNO. The increase in RSNO may result from
      increased NO production and/or decreased RSNO decomposition.

PMID- 12500092
TI  - In vivo excitotoxicity induced by ouabain, a Na+/K+-ATPase inhibitor.
AB  - The susceptibility of immature rat brain to neurotoxicity of N-methyl-D-aspartate
      (NMDA) has provided a widely used paradigm to study excitotoxicity relevant to
      acute neurodegenerative diseases such as cerebral ischemia. In this study,
      excitotoxicity was induced via injection of ouabain (1 mM/0.5 microL), a Na+/K+ 
      ATPase-inhibitor, into neonatal rat brain and compared with NMDA injection. The
      aim of the study was to induce excitotoxicity secondary to cellular membrane
      depolarization, thereby more closely mimicking the pathophysiologic processes of
      ischemia-induced brain injury where NMDA-receptor overstimulation by glutamate
      follows, not precedes, membrane depolarization. Na+/K+ -ATPase-inhibition caused
      an acute, 40% +/- 8% decrease of the apparent diffusion coefficient (ADC) of
      water, as measured using diffusion-weighted magnetic resonance imaging (MRI), and
      resulted in infarctlike lesions as measured using T2-weighted MRI and histology
      up to 2 weeks later. Localized one- and two-dimensional 1H-magnetic resonance
      spectroscopy (MRS) demonstrated that the early excitotoxic diffusion changes were
      not accompanied by an overall metabolic disturbance. Furthermore, 31P-MRS
      demonstrated that energy depletion is not a prerequisite for ADC decrease or
      excitotoxic cell death. Treatment with the NMDA-antagonist MK-801 (1 mg/kg)
      attenuated the volume of tissue exhibiting a decreased ADC (P < 0.005),
      demonstrating that the ouabain-induced injury is indeed excitotoxic in nature.
      The authors argue that, compared with NMDA-injection, ouabain-induced
      excitotoxicity elicits more appropriate glutamate-receptor overstimulation and is
      better suited to detect relevant neuroprotection in that it is more sensitive to
      attenuation of synaptic glutamate levels.

PMID- 12500093
TI  - Delayed treatment with MLN519 reduces infarction and associated neurologic
      deficit caused by focal ischemic brain injury in rats via antiinflammatory
      mechanisms involving nuclear factor-kappaB activation, gliosis, and leukocyte
      infiltration.
AB  - Secondary brain injury due to ischemia includes the infiltration of leukocytes
      into the brain parenchyma mediated by activation of nuclear factor-kappaB (NF
      kappaB), which is activated by proteasome degradation. Neuroprotection with the
      proteasome inhibitor MLN519 has previously been reported to decrease ischemic
      brain injury in rats. The authors used higher doses of MLN519 to evaluate the
      neuroprotection therapeutic window after 24 hours of brain injury in rats as
      correlated to proteasome levels, activated NF-kappaB immunoreactivity, and
      leukocyte infiltration. Male Sprague-Dawley rats were subjected to 2-hour middle
      cerebral artery occlusion (MCAO) and recovery. MLN519 or vehicle was administered
      after injury with a single injection given in delayed increments of 2 hours
      (i.e., 4, 6, or 8 hours after MCAO). Treatment with MLN519 up to 6 hours after
      MCAO (4 hours after reperfusion) effectively reduced neuronal and astrocytic
      degeneration, decreased cortical infarct volume, and increased neurologic
      recovery. These effects were related to >80% reductions in blood proteasome
      levels, reduced neutrophil infiltration, and a decrease in activated NF-kappaB
      immunoreactivity. This improved neuroprotection profile and antiinflammatory
      effect of MLN519 provides an exciting avenue for potential treatment of focal
      ischemic brain injury in humans.

PMID- 12500094
TI  - Upregulation of mitochondrial base-excision repair capability within rat brain
      after brief ischemia.
AB  - The mechanism by which brief episodes of cerebral ischemia confer protection
      (tolerance) against subsequent prolonged ischemic challenges remains unclear, but
      may involve upregulation of cell injury repair capability. The mitochondrion is a
      key site for the regulation of cell death pathways, and damage to mitochondrial
      genes has been linked to a number of neurologic diseases and aging. Therefore,
      the authors examined the response of the DNA base excision repair (BER) pathway
      in rat brain mitochondria after either brief (tolerance-inducing) or prolonged
      (injury-producing) focal cerebral ischemia. Brief (30-minute) middle cerebral
      artery occlusion (MCAO) induced mild oxidative mitochondrial DNA damage and
      initiated a prolonged (up to 72-hour) activation above control levels of the
      principal enzymes of the mitochondrial BER pathway, including uracil DNA
      glycosylase, apurinic/apyrimidinic (AP) endonuclease, DNA polymerase-gamma, and
      DNA ligase. In contrast, prolonged (100-minute MCAO) ischemia induced more
      substantial mitochondrial oxidative DNA damage whereas elevation of BER activity
      was transient (approximately 1 hour), declining to less than control levels over
      the course of 4 to 72 hours. These data reveal the differences in BER capacity
      after brief or prolonged ischemia, which may contribute to the neuron's ability
      to resist subsequent ischemic insults.

PMID- 12500095
TI  - Implications of vascular endothelial growth factor, sFlt-1, and sTie-2 in plasma,
      serum and cerebrospinal fluid during cerebral ischemia in man.
AB  - The relation between cerebral ischemia and local release of angiogenic factors
      was investigated after subarachnoid hemorrhage (SAH) in humans. Time-dependent
      concentration-changes of vascular endothelial growth factor (VEGF), sFlt-1 and
      sTie-2 extracted from plasma, serum, and cerebrospinal fluid (ventricular,
      cisternal, and lumbar) were analyzed in 15 patients surgically treated for
      ruptured aneurysms of the anterior circulation (Hunt and Hess grades I-V). Data
      were related to brain Po2 (Pbro2) and cerebral energy metabolites (extracellular
      lactate, pyruvate, glutamate, and glycerin concentrations) as well as clinical
      and radiologic reference data. Delayed impairment of cerebral perfusion secondary
      to progressive microcirculatory alterations was associated with reduced local
      Pbro2 and energy metabolism (increased lactate-pyruvate ratio, glutamate and
      glycerine levels). Elevated serum/plasma and CSF concentrations of VEGF, sFlt-1,
      and sTie-2 matched the scale of ischemic tissue hypoxia. Excessive VEGF/sFlt-1
      and sTie-2 levels were related to Pbro2 values consistently less than 5 mm Hg,
      glutamate concentrations greater than 300 micromol/L, lactate-pyruvate ratio
      greater than 300, cerebral infarction, and reduced outcome (P < 0.01). Delayed
      microcirculatory impairment was mirrored by distinct elevation of cisternal and
      arterial VEGF and sFlt-1 concentrations, suggesting local induction of
      angiogenesis. Arterial levels of VEGF, sFlt-1, and sTie-2 reflect both extent and
      time course of compensatory, yet clinically inefficient, angiogenesis in the
      absence of general hypoxia.

PMID- 12500096
TI  - Prevention of impairment of cerebral blood flow autoregulation during acute stage
      of subarachnoid hemorrhage by gene transfer of Cu/Zn SOD-1 to cerebral vessels.
AB  - The present study determined whether gene transfer of human copper/zinc
      superoxide dismutase-1 (Cu/Zn SOD-1) prevented the autoregulatory impairment of
      CBF induced by subarachnoid hemorrhage (SAH). After application of recombinant
      adenovirus (100 microL of 1 x 10(10) pfu/mL, intracisternally) encoding human
      Cu/Zn SOD-1 3 days before experiments, Cu/Zn SOD-1 activity significantly
      increased in association with increase in Cu/Zn SOD-1 mRNA and protein expression
      in the cerebral vasculature of both sham-operated and SAH rats as determined by
      reverse transcriptase-polymerase chain reaction, Western blotting, and
      immunohistochemistry, and SAH-induced increase in superoxide anion was markedly
      reduced in accordance with increased nitric oxide production. In line with these
      findings, rats that received human Cu/Zn SOD-1 therapy showed the prominent
      restoration of blunted vasodilation of the pial artery in response to calcitonin
      gene-related peptide and levcromakalim, and the recovery of impaired
      autoregulatory vasodilation in response to acute hypotension, thereby leading to
      significant restoration of CBF autoregulation. These results provide a rational
      basis for application of Cu/Zn SOD-1 gene therapy for protection of the
      impairment of autoregulatory CBF during the acute stage of SAH.

PMID- 12500097
TI  - Estimation of cerebral perfusion reserve by blood oxygenation level-dependent
      imaging: comparison with single-photon emission computed tomography.
AB  - Measurement of cerebrovascular reserve capacity predicts the risk of ischemic
      insult in patients with major vessel occlusion. Blood oxygenation level-dependent
      (BOLD) imaging has the potential to estimate reserve capacity of the cerebral
      circulation noninvasively based on changes in the signal that reflect differences
      in the magnetic susceptibility of intravascular oxyhemoglobin and
      deoxyhemoglobin. The authors examined the feasibility of using the BOLD technique
      to assess cerebrovascular reserve capacity in patients with cerebrovascular
      occlusive disease by comparing results with an established method of measuring
      CBF. Ten patients with severe or complete occlusion of the internal carotid
      artery were compared with 17 healthy subjects to evaluate regional differences
      and identify variables that indicate a change in the BOLD signal. Dilation of
      cerebral vessels was induced by breath holding, and the R2* change was examined
      with gradient-echo, echo-planar imaging. Before measuring the regional change in
      the BOLD signal, actual timing of "activated" and "rest" periods was corrected by
      shifting the phase of a sine-wave template to obtain the largest correlation
      coefficient. Percent signal change was calculated on a pixel-by-pixel basis and
      was compared with CBF measured by single-photon emission computed tomography
      (SPECT) before and after acetazolamide challenge. The degree of impairment and
      the distribution of impaired areas detected by the BOLD study correlated with the
      results of SPECT. Overall sensitivity and specificity of the BOLD technique by
      visual inspection were 100% and 98.4%, respectively. A negative response
      (decreased CBF) frequently was observed in areas of exhausted reserve capacity,
      suggesting that a "steal" phenomenon exists. The percent change and the
      (Delta)CBF were well correlated (P < 0.01). The mean percent change in most areas
      of impaired reserve capacity was more than 2 SD below the mean values in healthy
      subjects. The present method of semiquantitative BOLD analysis can be used to
      create a map of the cerebral hemodynamic state. Furthermore, the development of
      reliable, generally accessible techniques for evaluating cerebral hemodynamics
      opens the door for clinical studies to monitor and treat patients with
      compromised reserve. This study is an attempt to develop such analysis.

PMID- 12500098
TI  - A proline-threonine substitution in codon 351 of ADH1C is common in Native
      Americans.
AB  - BACKGROUND: The alcohol dehydrogenase (ADH) genes have been repeatedly associated
      with protection against alcoholism. Until now, only four protein coding variants
      have been identified (ADH1C Arg271Gln, Ile349Val, ADH1B Arg47His, and Arg369Cys),
      and only two of these (ADH1CIle349Val and ADH1B Arg47His) have been routinely
      tested in association studies with alcoholism. METHODS: The new ADH1C*351Thr
      allele was identified by direct sequencing of DNA samples that gave different
      typing results for the ADH1C Ile349Val polymorphism with different typing
      protocols. RESULTS: A new coding variant has been identified at codon 351 of
      ADH1C. This allele is found in most Native American populations that we have
      studied with allele frequencies of the new ADH1C*351Thr allele as high as 26%.
      Only two instances of this allele have been seen in a large survey of African and
      Eurasian populations. CONCLUSIONS: The changes in charge, size, and rotational
      mobility caused by this amino acid substitution should be significant. Because
      this new variant codes for a new enzyme form in Native Americans, the kinetics of
      this enzyme should be studied and considered in studies of the role of in the
      protection against alcoholism in Native Americans.

PMID- 12500099
TI  - Acetylcholine and alcohol sensitivity of neuronal nicotinic acetylcholine
      receptors: mutations in transmembrane domains.
AB  - BACKGROUND: The effect of n-alcohols on glycine and gamma-aminobutyric acid type
      A receptors depends on two specific amino acids (AAs) located in the
      transmembrane domains (TM) 2 and 3. Our aim was to assess whether the
      corresponding AAs in the neuronal nicotinic acetylcholine receptor (nAChR) also
      formed a binding pocket for alcohols. METHODS: We made single AA substitutions in
      the homologous sites in rat neuronal nAChR alpha2 and alpha4 (alphaL261 and
      alphaL283) and expressed them in Xenopus laevis oocytes in combination with beta4
      wild type. The effect of different n-alcohols was studied in alpha4(L261A)beta4
      and alpha4(L283A)beta4 nAChRs. The effect of ethanol, propanol, and octanol on
      acetylcholine (ACh) responses was studied in alpha2(L261X)beta4 and
      alpha2(L283X)beta4 nAChRs. RESULTS: Most of the mutations in the alpha2 subunit,
      in either the 261 or the 283 position, induced changes in ACh sensitivity and
      increased alcohol action, but none was able to reduce ethanol potentiation. In
      alpha4(L283A)beta4, enhancement of potentiation by short-chain alcohols was
      observed, as well as a change from inhibition to potentiation for long-chain
      alcohols. The exposure of the AAs was assessed through the action of a charged
      thiol-specific reagent on alpha2(L261C)beta4 and alpha2(L283C)beta4, and these
      experiments suggest that the AA in TM2 is located in a water-accessible position,
      whereas the AA in TM3 is inaccessible. However, a noncharged thiol-specific
      reagent did not affect either ACh responses or ethanol effect on
      alpha2(L261C)beta4. CONCLUSIONS: The AAs located at positions 261 and 283 of the
      alpha2 and alpha4 nAChR subunits do not seem to form a binding pocket for
      alcohols. Additional studies are required to determine whether alcohols act on a
      site near these AAs or on sites unrelated to the TM2-TM3 site found in glycine
      and gamma-aminobutyric acid type A receptors.

PMID- 12500100
TI  - Binge drinking in Jewish and non-Jewish white college students.
AB  - BACKGROUND: In the United States, religious commitment, as measured by service
      attendance, has an inverse relationship with alcohol consumption, heavy use, and
      problem use. This association, however, has not been found consistently in Jewish
      Americans. The present study examined the relationship between religious
      variables and binge drinking in Jewish and non-Jewish white college students. In
      addition, the association among genetic, cultural, and religious variables and
      binge drinking was examined in the Jewish sample alone. METHODS: Participants
      were 132 Jewish and 147 non-Jewish white college students. All participants
      completed the Time-Line Follow-Back, had blood drawn for genotyping at the
      alcohol dehydrogenase locus ADH2, and reported their religious affiliation and
      the number of religious services attended in the past year. Jewish subjects also
      completed the Jewish Identity Scale. RESULTS: As hypothesized, more frequent
      religious service attendance related to lower rates of binge drinking in non-Jews
      but was not related to binge drinking in Jews. Within the Jewish sample,
      individuals who were religiously affiliated had approximately one third the risk
      of binge drinking as those who were secularly affiliated, but identification with
      Jewish culture was not related to binge drinking. In the total sample,
      individuals who possessed a variant alcohol dehydrogenase allele ADH2*2 were
      approximately half as likely to binge drink as those who did not possess this
      allele. CONCLUSIONS: These results are consistent with previous studies that find
      an inverse relationship between religious service attendance and heavy alcohol
      use in Christian but not Jewish college students. Findings within the Jewish
      sample support theories that suggest religious, not just cultural, Jewish
      affiliation relates to lower levels of alcohol behavior. More research is needed
      to identify additional factors, including other religious, cultural, genetic, and
      biological influences, that protect Jewish Americans from heavy drinking.

PMID- 12500101
TI  - Acamprosate inhibits the binding and neurotoxic effects of trans-ACPD, suggesting
      a novel site of action at metabotropic glutamate receptors.
AB  - BACKGROUND: Several reported effects of acamprosate within the glutamatergic
      system could result from interactions with metabotropic glutamate receptors
      (mGluRs). The following experiments were performed to determine whether
      acamprosate could compete with trnas-ACPD (+/--1-aminocyclopentane-trans-1,3
      dicarboxylic acid, an equimolecular mixture of 1S, 3R and 1R, 3S-ACPD and an
      agonist at both group I and group II mGluRs) sensitive binding sites and protect
      against trans-ACPD-induced neurotoxicity in organotypic hippocampal slice
      cultures. METHODS: A P2 membrane preparation of cortices, cerebellums, and
      hippocampi of adult, male Sprague Dawley rats was used to determine the abilities
      of N-methyl-D-aspartic acid (NMDA) and trans-ACPD to displace [3H]glutamate in
      both the absence and the presence of the sodium salt of acamprosate (sodium mono
      N-acetyl homotaurine or Na-acamprosate). A comparison of the effects of 100
      microM guanosine 5'-triphosphate on unlabeled glutamate, trans-ACPD, and Na
      acamprosate was performed in the same paradigm. For the neurotoxicity studies,
      organotypic hippocampal slice cultures from male and female 8-day-old neonatal
      rats were exposed to either 500 microM -ACPD or 50 microM NMDA for 24 hr in
      normal culture medium containing serum on day 20 in vitro. The effects of Na
      acamprosate and 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893), a noncompetitive
      antagonist at metabotropic type 5 receptors (mGluR5s), were assessed by
      determining differences in propidium iodide uptake as compared with neurotoxic
      challenges alone. RESULTS: Na-acamprosate displaced 31% of [3H]glutamate but did
      not compete with NMDA for [3H]glutamate binding sites. Na-acamprosate displayed
      total competition with trans-ACPD. The presence of 100 microM guanosine 5'
      triphosphate differentially altered the displacing capabilities of the two mGluR
      agonists, unlabeled glutamate and trans-ACPD, as compared with Na-acamprosate. Na
      acamprosate (200-1000 microM) and SIB-1893 (20-500 microM) both were
      neuroprotective against trans-ACPD induced neurotoxicity that likely results from
      mGluR potentiation of NMDARs. In turn, Na-acamprosate and SIB-1893 had no direct
      effects on NMDA-induced neurotoxicity. CONCLUSIONS: Na-acamprosate demonstrates
      the binding and functional characteristics that are consistent with a group I
      mGluR antagonist. The functional similarities between Na-acamprosate and SIB-1893
      support an interaction of Na-acamprosate at mGluR5s. The neuroprotective
      properties of acamprosate and possibly its ability to reduce craving in alcohol
      dependent patients may result from its alterations in glutamatergic transmission
      through mGluRs.

PMID- 12500102
TI  - Differential effects of alcohol consumption on eukaryotic elongation factors in
      heart, skeletal muscle, and liver.
AB  - BACKGROUND: Acute and chronic alcohol administration diminishes rates of protein
      synthesis in a variety of tissues including skeletal muscle, heart, and liver,
      through a diminished translational efficiency rather than a reduction in the
      number of ribosomes. METHODS: The purpose of the present study was to examine the
      effect of chronic alcohol exposure (8, 12, or 16 weeks) on elongation factors
      (eEF) as a potential mechanism for controlling mRNA translation in psoas, soleus,
      heart, and liver. The cellular content of eEF1A and eEF2 and the phosphorylation
      state of eEF2 in each tissue was measured using immunoblot techniques. RESULTS:
      The protein content of eEF1A was reduced in psoas, heart, and liver (but not
      soleus) from rats fed a diet containing alcohol for 16 weeks, but not for 8 or 12
      weeks, compared with time-matched pair-fed controls. eEF2 content was only
      reduced in myocardium after feeding rats an alcohol-containing diet for 16 weeks.
      In other tissues, no change in eEF2 content was observed. The decreases in eEF
      protein content were not associated with a concomitant reduction in the mRNA
      abundance for eEF1A or eEF2. The phosphorylation state of eEF2 was not affected
      by chronic alcohol consumption in the skeletal muscle or heart. In contrast, the
      level of eEF2 phosphorylation in the liver was reduced after 8, 12, and 16 weeks
      of feeding rats an alcohol-containing diet. In contrast, acute alcohol
      intoxication failed to modulate the content of eEF1A or eEF2 in any of the
      tissues examined. The phosphorylation state of eEF2 was reduced in psoas
      following acute alcohol intoxication. CONCLUSIONS: A decreased eEF1A protein
      content could account, in part, for the inhibition of translational efficiency
      following chronic (16 weeks) alcohol feeding but not the response to acute
      alcohol intoxication.

PMID- 12500103
TI  - Short of complete abstinence: an analysis exploration of multiple drinking
      episodes in alcoholism treatment trials.
AB  - BACKGROUND: In alcoholism treatment clinical trials, conventional analysis of
      efficacy outcomes often focuses on the time to a first event, where the event may
      be "any drinking", "safe (or low risk) drinking", "moderate drinking" or "heavy
      drinking," in addition to multiple outcomes such as frequency of drinking days,
      percent abstinence days, etc. METHODS: We consider the multivariate failure time
      analytic methods. In alcoholism treatment trials, the naturalistic course of
      drinking behavior during treatment intervention often presents with a gradual
      change in drinking before the emergence of a more stable drinking or abstinence
      pattern. Thus, for each subject, evaluation of all drinking events, and
      incorporating the event times over a defined duration, may give a more
      comprehensive description of his/her drinking pattern. As a consequence, the
      efficacy of a new treatment for alcoholism may be elevated with greater
      statistical sensitivity. RESULTS: The utility of the multiple failure time method
      is demonstrated via a real case study for evaluation of alcoholism treatments.
      The multiple event time analyses showed that the risk of having "any drinking
      days" or "heavy drinking days" during the entire duration of the study was
      significantly lower with experimental treatment than with placebo. Further
      explorations showed that the treatment effect was primarily observed in the later
      relapse events and not the first event with respect to relapse to any drinking
      episodes. Such effect would have missed using the traditional time to first event
      analysis approach. The observed effect of treatment with respect to relapse to
      multiple heavy drinking episodes was shown not only in the first event but also
      in the later events. CONCLUSION: The multiple failure time approach may be
      applicable when 'drinking failure' is variously defined as a single drink, one at
      risk drinking day, one heavy drinking day, or one alcohol-related social,
      occupational or medical problem. If "a drinking episode" is properly defined and
      the design gains statistical efficiency, the multiple event analytic strategy
      should provide improved statistical power to detect treatment effects.

PMID- 12500104
TI  - Sodium sensitivity as a main determinant of blood pressure changes during early
      withdrawal in heavy alcoholics.
AB  - BACKGROUND: Stimulated sympathetic nervous system, renin-angiotensin-aldosterone
      system, vasopressin, and cortisol are thought to affect blood pressure in early
      withdrawal of alcoholics. Hyperactivity of sodium-retaining systems with
      consequent volume expansion also could interact with sodium sensitivity as
      previously found in long-term withdrawing alcoholics. METHODS: To investigate
      this hypothesis, blood pressure and sodium balance were measured during the first
      8 days of withdrawal in 18 chronic alcoholics on a 150 mM Na diet. Results were
      related to the Salt Sensitivity Index of blood pressure as measured in the same
      alcoholics after 1 year of abstinence. RESULTS: Early withdrawal study: there was
      a positive sodium balance (+288.6 +/- 45.6 mM; p < 0.0001) and rise in mean
      arterial pressure (+11.8 +/- 2.9 mm Hg; p = 0.001) during early withdrawal on 150
      mM Na diet. Salt Sensitivity Study after long-term detoxification: the shift from
      low (55 mM) to high sodium (260 mM) intake produced a larger (p = 0.04) increase
      in mean arterial pressure in alcoholics (+9.3 +/- 2.0 mm Hg) than in 30 teetotal
      controls (+5.1 +/- 1.1) (Salt Sensitivity Index, 0.047 +/- 0.008 vs. 0.023 +/-
      0.0053; p < 0.05). Changes in mean blood pressure during withdrawal were highly
      related to sodium sensitivity index (r = 0.8; p < 0.001). CONCLUSIONS: Early
      withdrawing alcoholics exposed to a normal sodium intake experience positive Na
      balance and increase in blood pressure that is related to sodium sensitivity
      measured after long-term detoxification. This suggests that salt sensitivity
      plays a key role in blood pressure regulation in early withdrawing alcoholics.

PMID- 12500105
TI  - Long-term effects of and physiological responses to nitrous oxide gas treatment
      during alcohol withdrawal: a double-blind, placebo-controlled trial.
AB  - BACKGROUND: Nitrous oxide gas (N2O) has been proposed to be effective in the
      treatment of the alcohol withdrawal syndrome (AWS). This has not been proved,
      however, in studies performed according to good clinical practice guidelines.
      Moreover, previous studies have not measured end tidal N2O concentrations or
      physiologic responses during N2O treatment. We have recently reported that in a
      double-blind, randomized, controlled setting, N2O was not superior to placebo in
      relieving AWS symptoms. In this previous study, we did not find significant
      differences between the treatments either in the Clinical Institute Withdrawal
      Assessment of Alcohol scores or in the total use of benzodiazepines (diazepam and
      temazepam). The aim of the present study was to characterize other effects and
      side effects of the N2O treatment using several objective measures and to study
      the possible long-term efficacy of the treatment. METHODS: A total of 105
      inpatients who had AWS and were admitted to the A-Clinic detoxification center
      were included in the study. The subjects were randomly assigned to one of the
      following three treatments: (1) N2O/oxygen (from 30 to 70% in oxygen), (2)
      air/oxygen (30%/70%), and (3) medical (normal) air. During the single 45-min
      treatment period, end-tidal N2O, carbon dioxide, and oxygen concentrations were
      measured. The physiologic responses were studied by measuring heart rate, blood
      pressure, pulse oximetric saturation, frontal muscle electromyographic activity,
      and plethysmographic pulse amplitude. Long-term effects were studied by measuring
      craving with the Obsessive-Compulsive Drinking Scale; severity of dependency with
      Severity of Alcohol Dependence Data; and liver enzymes with aspartate
      aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase 3 and 6
      months after the treatment. RESULTS: Patients in the N2O group demonstrated
      significantly higher facial muscle electromyographic activity and higher pulse
      amplitude than the air-treated subjects. Self-reported side effects between the
      gas treatments, however, did not differ between the groups. Regarding long-term
      effects of the treatments, there were no differences between the groups.
      CONCLUSIONS: Contrary to previously published data, N2O treatment did not
      decrease craving or liver enzymes during the 6-month follow-up. At the
      concentration used, N2O treatment produced signs of arousal instead of strong
      sedation.

PMID- 12500106
TI  - Drinks of the father: father's maximum number of drinks consumed predicts
      externalizing disorders, substance use, and substance use disorders in
      preadolescent and adolescent offspring.
AB  - BACKGROUND: The maximum number of drinks consumed in 24 hr seems to be an
      interesting phenotype related to alcoholism. The goal of the present study was to
      determine in an epidemiologic sample whether this measure of drinking history in
      fathers predicted externalizing behavioral disorders, substance use, and
      substance abuse in preadolescent and adolescent offspring and whether any such
      associations would be independent of paternal alcohol dependence diagnoses.
      METHODS: Subjects were male and female twins from both age cohorts of the
      Minnesota Twin Family Study, a population-based longitudinal study, and were
      approximately 11 or 17 years of age, respectively, upon study enrollment. In both
      age cohorts, diagnoses of conduct disorder, oppositional defiant disorder, and
      attention-deficit/hyperactivity disorder served as outcome measures. In addition,
      measures of lifetime substance use and of the presence of symptoms of substance
      abuse were derived for the 11-year-old cohort when subjects were approximately 14
      years old and diagnoses of substance abuse were derived for the older cohort at
      age 17. An extension of logistic regression using generalized estimating
      equations served to assess whether paternal maximum alcohol consumption predicted
      filial outcome measures. RESULTS: Paternal maximum alcohol consumption was
      consistently associated with conduct disorder, substance use, and substance abuse
      or dependence in male and female offspring. These associations were not mediated
      by a primary effect of paternal alcoholism. CONCLUSIONS: Paternal maximum alcohol
      consumption was uniquely associated with those offspring characteristics most
      reliably found in adolescent children of alcoholic parents. This phenotype might
      supplement DSM diagnoses of alcohol dependence to reduce the number of false
      positives in genetic research.

PMID- 12500107
TI  - Alcohol is the main factor in excess traffic accident fatalities in France.
AB  - BACKGROUND: The aim of this study was to better evaluate the role of alcohol
      drinking in fatalities linked to road traffic accidents. METHODS: The data of
      accidents were collected by a French official agency from police records,
      including many variables, among which was a blood alcohol test. They were
      analyzed in a descriptive way and toward a logistic regression. This exhaustive
      database comprised all of the 500,961 accidents with casualties that involved
      less than three vehicles (28,506 fatal accidents) recorded in France during a 52
      month period (September 1995 to December 1999). The results of the alcohol tests
      were known in 78.7 of the drivers. RESULTS: The blood alcohol concentration was
      over the legal limit (0.50 g/L in France) in 9.8% of the accidents with
      casualties overall. Considering only fatal accidents, the rate of positive
      alcohol test in drivers was approximately 31.5%. This rate varied depending on
      the period and the type of accident, raising up to 71.2% in single-vehicle
      accidents (loss of control) at night during the weekend. The percentage of
      positive alcohol tests also dramatically increased following the number of
      fatalities per accident (87.5% in single-vehicle accidents during weekend nights
      involving three or more killed). The logistic regression in single-vehicle
      accident shows that the higher odds ratios concern the positive blood alcohol
      test (OR = 4.19), clearly overwhelming the other precipitating factors of
      accidents (age of driver, meteorological conditions, time of day, and other
      factors). CONCLUSIONS: Drinking alcohol before driving is a well known factor of
      accidents. We clearly demonstrate here that it is the main factor leading to
      deaths linked to road traffic accidents in France. The results are strengthened,
      and some analyses are allowed, by the exceptional features of our database. The
      authors emphasize the need for prevention measures.

PMID- 12500108
TI  - Effects of chronic hepatic dysfunction on pulmonary glutathione homeostasis.
AB  - BACKGROUND: The development of acute respiratory distress syndrome (ARDS) in
      patients with pre-existing cirrhosis of the liver is associated with very high
      mortality. One possible cause may be alteration of pulmonary antioxidant capacity
      as a result of chronic hepatic dysfunction. Glutathione (GSH) is the most
      substantial nonprotein thiol in living organisms and likely plays a key role in
      neutralizing the oxidants and reactive oxygen species that are increased in ARDS.
      The lung is unable to synthesize GSH and is dependent on the liver. During
      periods of oxidant stress, individuals may exhibit relative deficiencies of GSH.
      With cirrhosis, the end result of chronic alcohol ingestion, this deficiency is
      more profound. METHODS: Sixteen stable subjects with cirrhosis primarily due to
      alcohol consumption and 15 healthy controls underwent bronchoscopy and
      bronchoalveolar lavage with concurrent measurement of GSH in the plasma and the
      alveolar epithelial lining fluid (ELF). RESULTS: For standardizing for saline
      dilution of the epithelial lining fluid as a result of bronchoalveolar lavage,
      GSH values are expressed in relation to immunoglobulin A (IgA). GSH in the ELF
      was profoundly reduced in the cirrhotic group [12.5 microg of GSH per microg of
      IgA (5.3-16.9 microg)] compared with the control group [64.0 microg of GSH per
      microg of IgA (55.1-242.5 microg); < 0.001]. The ratio of oxidized GSH to total
      GSH in the ELF was also significantly increased in the cirrhotic group [9.2% (5.1
      16.4%) vs. 3.4% (1.7-5.7%); p < 0.003]. CONCLUSIONS: Despite a total reduction in
      GSH concentrations in the alveolar epithelial lining fluid of individuals with
      cirrhosis, the amount of oxidized GSH is increased. There is increased
      utilization of GSH despite the low supply in stable individuals with cirrhosis
      during steady state. These perturbations in GSH homeostasis in the alveolar
      epithelial lining fluid may be a factor in the poor outcomes seen in these
      individuals with ARDS.

PMID- 12500109
TI  - Alcohol unmasks simian immunodeficiency virus-induced cognitive impairments in
      rhesus monkeys.
AB  - BACKGROUND: Alcohol and human immunodeficiency virus (HIV) produce similar
      neuropathological profiles, including loss of neurons in the frontal cortex.
      Additionally, HIV-positive patients with a history of alcohol abuse have greater
      neurologic deficits, and chronic alcohol abuse produces electrophysiological
      deficits earlier in the HIV disease process. Few studies, preclinical or
      clinical, have examined whether alcohol administration exacerbates the
      neuropsychological deficits in subjects with lentiviruses such as HIV. METHODS:
      To examine the combined effects of alcohol and immunodeficiency viruses (IVs) on
      neuropsychological functioning, four groups of young adult rhesus monkeys trained
      to respond under two complex behavioral tasks were administered ethanol 4 days
      per week via an intragastric catheter for 3 months and then infected with simian
      immunodeficiency virus (SIV). Behavioral testing after SIV inoculation was
      conducted in each group (-ethanol [EtOH]/-SIV, -EtOH/+SIV, +EtOH/-SIV, and
      +EtOH/+SIV) on days when alcohol was not administered to avoid a direct confound
      and on several occasions when ethanol or sucrose was administered as a probe of
      the effect of alcohol alone and the effect of caloric supplementation on the food
      maintained tasks, respectively. RESULTS: During the days of the week when ethanol
      was not administered, little or no disruption was observed in either response
      rate or the percentage of errors (accuracy) across the different treatment
      groups. In contrast, behavioral testing during alcohol administration revealed
      that subjects in the various treatment groups had different susceptibilities to
      ethanol administration. As expected, a two-way ANOVA (ethanol condition, SIV
      condition) indicated there were significant main effects of ethanol on both
      response rate and percent errors in both behavioral tasks, but it also indicated
      there was a significant interaction between ethanol administration and SIV
      infection on the accuracy of responding in the acquisition (learning) task. In
      addition, the main effect of SIV on percent errors was in the performance task.
      CONCLUSIONS: The fact that alcohol administration in SIV-infected monkeys
      produced greater behavioral deficits than either alcohol or SIV alone further
      strengthens the supposition that IVs adversely affect neural substrates involved
      in cognition and that the adverse effects of many central nervous system drugs
      may be enhanced in IV-infected individuals.

PMID- 12500110
TI  - Muscle antioxidant status in chronic alcoholism.
AB  - BACKGROUND Chronic myopathy due to excessive ethanol intake is one of the most
      frequent causes of acquired skeletal myopathy in developed countries. Its
      pathogenesis is multi-factorial, only partially clarified, and antioxidant
      imbalance has been suggested to influence its development, being a type II
      glucolytic, fast-twitch fiber subset more sensitive to this effect. METHODS: We
      assessed superoxide dismutase, glutathione peroxidase, and glutathione reductase
      enzyme activities as well as the total antioxidant status capacity in muscle
      samples obtained from 41 chronic alcoholic males and 12 age-matched controls.
      Alcoholic skeletal myopathy was defined according to standard histologic
      criteria. We evaluated the influence of ethanol consumption, caloric and protein
      nutritional status, and the presence of skeletal myopathy with the tissue
      activities of these antioxidant enzymes. RESULTS: Chronic alcoholics showed a 16%
      reduction in glutathione peroxidase and a 13% increase of superoxide dismutase in
      the skeletal muscle, compared with controls (p < 0.05, both). Muscle antioxidant
      changes in chronic alcoholics were not related to the presence of skeletal
      myopathy, parameters of alcohol consumption, or conventional nutritional
      parameters. CONCLUSIONS: Antioxidant muscle enzyme activities are partially
      disturbed in chronic alcoholism, although not related to the presence of
      myopathy, amount of ethanol consumed, or the nutritional status of the patients.
      Further studies should assess other aspects not included in the present study
      such as muscle site-specific changes in antioxidant status/oxidative damage,
      specific fiber-type sensitivity to alcohol, and type and quantity of antioxidant
      content of the diet or in the alcohol beverages.

PMID- 12500111
TI  - Interhemispheric transfer in children with heavy prenatal alcohol exposure.
AB  - BACKGROUND: Prenatal alcohol exposure has long been associated with alterations
      in brain structure and behavioral changes. The corpus callosum can be affected by
      heavy prenatal alcohol exposure, and agenesis (absence) of this structure occurs
      more often in children with fetal alcohol syndrome than in the general population
      or in other developmentally delayed populations. Although the majority of
      children with fetal alcohol syndrome do not have agenesis of the corpus callosum,
      callosal area is reduced in this population, particularly in the anterior and
      posterior regions. However, the functional implication of these size reductions
      has not been examined. METHODS: The current study used a finger localization task
      to measure the transfer of information across the corpus callosum in children and
      adolescents with histories of heavy prenatal alcohol exposure and age- and sex
      matched controls. In a subset of children, correlational analysis was also
      conducted between behavioral data and cross-sectional area of the corpus
      callosum. RESULTS: When compared with nonexposed controls, alcohol-exposed
      children made more errors on trials for which information had to cross the corpus
      callosum ("crossed" trials) than on trials for which it did not ("uncrossed"
      trials), and they also made more errors as the task increased in complexity.
      Additionally, correlations with magnetic resonance imaging data in a subset of
      children revealed that impairment in interhemispheric transfer was related to
      reductions in the size of the corpus callosum. These correlations were
      independent of effects expected from the relationship between corpus callosum
      size and general intellectual functioning alone. CONCLUSIONS: These findings
      suggest that children with heavy prenatal alcohol exposure display subtle
      deficits in the interhemispheric transfer of information in the somatosensory
      domain. Such deficits in interhemispheric transfer are likely to be related to
      the myriad of other behavioral and cognitive impairments observed in these
      children.

PMID- 12500112
TI  - Inhibition of NF-kappa B binding correlates with increased nuclear glucocorticoid
      receptor levels in acute alcohol-treated human monocytes.
AB  - BACKGROUND: Acute alcohol treatment blocks inflammatory cytokines via inhibition
      of NF-kappaB in monocytes in the presence of ongoing IkappaBalpha degradation,
      suggesting regulation of NF-kappaB activation downstream of IkappaBalpha
      degradation. DNA binding of NF-kappaB has been suggested to be regulated by other
      nuclear regulatory factors, including the glucocorticoid receptor (GR). Here, we
      show for the first time that acute alcohol (25 mM) exposure modulates GR
      activation in monocytes. METHODS: Human peripheral blood monocytes were treated
      with lipopolysaccharide (LPS) in the presence or absence of alcohol (25 mM) for 1
      hour. Nuclear GR levels were estimated by Western blotting and NFkappaB
      activation was studied in the same extracts by gel shift analysis (EMSA). Cells
      were stimulated with 1 microM of Dex to be used as positive control for GR
      activation. GR/GRE binding was also determined in nuclear extracts by EMSA.
      IkappaBalpha mRNA known to be induced by GR/GRE activation was studied in total
      RNA extracts by the SuperArray method (SuperArray Inc., Bethesda, MD). RESULTS:
      LPS is a potent inducer of GR nuclear translocation and GR binding to the
      glucocorticoid response element (GRE). Acute alcohol treatment both induced (p <
      0.05) and augmented (p < 0.05) LPS-stimulated GR nuclear levels. However, alcohol
      inhibits LPS-induced (nonligand bound) GR/GRE binding activity in monocytes. This
      inhibition of GR transactivation by alcohol was further confirmed by decreased
      expression (40%) of a target gene, IkappaBalpha. Thus, alcohol treatment
      increases nonligand-bound nuclear GR, but inhibits its transactivation function.
      Ligand-induced GR/GRE binding was decreased in alcohol-treated monocytes.
      Inhibition of ligand-induced GR/GRE binding by alcohol exposure is likely due to
      cytoplasmic retention of the GR. CONCLUSIONS: Our results show that acute alcohol
      exposure inhibits GR in monocytes by differently affecting ligand- and nonligand
      induced GR nuclear translocation. These data also suggest that acute alcohol
      regulates GR activation in monocytes concomitant to inhibition of NF-kappaB
      activation.

PMID- 12500113
TI  - Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes.
AB  - BACKGROUND: Acute and chronic alcohol abuse impairs various functions of the
      immune system and thus has been implicated as a cofactor in HIV infection. The
      mechanisms by which alcohol affects the function of human immune cells that are
      the targets for HIV are unknown. METHODS: Human blood monocyte-derived
      macrophages (MDM) were incubated with or without alcohol (10-40 mM) for 24 hr and
      then infected with HIV for 24 hr. Culture supernatants were harvested for HIV
      reverse transcription assay. HIV entry receptor (CCR5, CD4, and CXCR4) expression
      was determined by reverse transcription-polymerase chain reaction and flow
      cytometry assays. Beta-chemokines were analyzed using enzyme-linked immunosorbent
      assay. Different HIV strains (Bal, SF-162, 89.6, and UG024) were used for
      infection experiments. In addition, ADA (macrophage-tropic strain) and murine
      leukemia virus envelope-pseudotyped HIV infection was carried out. RESULTS:
      Although alcohol had little effect on HIV T-lymphocyte-tropic strain infection,
      it significantly enhanced HIV R5 strain infection in MDM. The enhancing effect of
      alcohol on the HIV R5 strain was further evidenced by the observation that the R5
      (ADA) strain envelope-pseudotyped HIV infection is markedly increased by alcohol,
      whereas murine leukemia virus envelope-pseudotyped HIV infection was not
      affected. Alcohol significantly up-regulated CCR5 receptor expression and
      inhibited the endogenous production of beta-chemokines by MDM. CONCLUSION:
      Alcohol, through the down-regulation of beta-chemokine production and the up
      regulation of CCR5 receptor expression, enhances HIV R5 strain infection of MDM
      and may have an important role as a cofactor in the progression of HIV disease.

PMID- 12500114
TI  - Timing accuracy and variability in children with prenatal exposure to alcohol.
AB  - BACKGROUND: Prenatal exposure to alcohol (prenatal alcohol exposure) is
      associated with gross and fine motor skill dysfunction. The present study
      examined performance on two types of timing tasks to determine the extent to
      which prenatal alcohol exposure affects perception, movement planning, and
      movement execution during tasks that require temporal processing. METHODS:
      Fourteen children with confirmed heavy prenatal alcohol exposure and 22 control
      children (aged 5-10 years) completed two timing tasks: a coincident-anticipation
      timing task that primarily assessed central processing, and a movement-speed
      timing task that evaluated the motor component of temporal processing. Absolute
      error, signed error, and variability of the participant's signed error were the
      dependent variables. RESULTS: For both timing tasks, children with prenatal
      alcohol exposure were significantly less accurate and more variable than control
      children, indicating that both the sensory-perceptual and motor components of
      temporal processing were disrupted in alcohol-exposed children. CONCLUSIONS:
      Alcohol-exposed children had difficulty producing accurate and consistent motor
      responses when intercepting a moving target or moving through a spatial target in
      a specified amount of time. Disruptions in these motor timing behaviors may be
      indicative of alcohol-related cerebellar or basal ganglia damage.

PMID- 12500115
TI  - Modulation of immunity and viral-host interactions by alcohol.
AB  - This manuscript represents the proceedings of a symposium at the 2001 RSA Meeting
      in Montreal, Canada. The organizers/chairs were Gyongyi Szabo and Geoffrey M.
      Thiele. The presentations were (1) Introduction, by Gyongyi Szabo; (2) Chemokine
      dysregulation after acute ethanol exposure, by Elizabeth J. Kovacs; (3) Chemokine
      production and innate immunity in the livers of simian immunodeficiency virus
      infected Macaca mulatta following chronic alcohol administration, by Abraham P.
      Bautista; (4) Influence of ethanol consumption on the severity and progression of
      hepatitis associated with cytomegalovirus infection, by Laura Sosa and Thomas R.
      Jerrells; (5) Scavenger receptor involvement in the immune response to the
      metabolites of chronic ethanol ingestion, by Geoffrey M. Thiele; and (6)
      Mechanisms of impaired accessory cell functions due to alcohol exposure and
      hepatitis C infection, by Gyongyi Szabo.

PMID- 12500116
TI  - Alcohol and Tobacco: Mechanisms and Treatment. Proceedings of a workshop.
      Bethesda, Maryland, USA. May 6-7, 2002.

PMID- 12500117
TI  - Animal models as a tool for studying mechanisms of co-abuse of alcohol and
      tobacco.

PMID- 12500118
TI  - Effects of nicotine on alcohol consumption.

PMID- 12500119
TI  - Ethanol and nicotine: a pharmacologic balancing act?

PMID- 12500121
TI  - Interactions between alcohol and nicotine dependence: a summary of potential
      mechanisms and implications for treatment.

PMID- 12500120
TI  - Shared genetic vulnerability in alcohol and cigarette use and dependence.

PMID- 12500122
TI  - The effects of alcohol on cigarette craving.

PMID- 12500123
TI  - Cue reactivity in alcohol and tobacco dependence.

PMID- 12500124
TI  - Potentiation of nicotine reward by alcohol.

PMID- 12500125
TI  - Independent alcohol and tobacco effects on stress axis function.

PMID- 12500126
TI  - Do smokers with current or past alcoholism need different or more intensive
      treatment?

PMID- 12500127
TI  - Self-change and dual recoveries among individuals with alcohol and tobacco
      problems: current knowledge and future directions.

PMID- 12500128
TI  - Pharmacotherapy for alcoholic smokers.

PMID- 12500129
TI  - Role of naltrexone in initial smoking cessation: preliminary findings.

PMID- 12500130
TI  - Timing of alcohol and smoking cessation study.

PMID- 12500131
TI  - Treating alcoholic smokers who have a history of depression.

PMID- 12500132
TI  - Brief interventions for smoking cessation in alcoholic smokers.

PMID- 12500133
TI  - In vivo assessment of the effects of smoking cessation in alcoholic smokers.

PMID- 12500134
TI  - Alcohol and tobacco: clinical and treatment issues.

PMID- 12500135
TI  - [Neurovascular units and the healthcare network: perspectives for stroke victims]

PMID- 12500136
TI  - [Magnetization transfer imaging techniques in multiple sclerosis patients: state
      of the art]

PMID- 12500137
TI  - [Human neurotoxicity of ethylene-bis-dithiocarbamates (EBDC)]

PMID- 12500138
TI  - [Wernicke-Korsakoff syndrome: diagnostic contribution of magnetic resonance
      imaging]

PMID- 12500140
TI  - [Cervical spondylotic myelopathy: motor and somatosensory evoked potentials,
      clinical and radiological correlations]

PMID- 12500141
TI  - [Aphasic hypergraphy in the course of a bihemispheric glioblastoma]

PMID- 12500142
TI  - [Central nervous system involvement in patients with hepatitis C infection]

PMID- 12500143
TI  - [Meningismus after taking kava-kava]

PMID- 12500144
TI  - [Thyrotoxicosis periodic hypokaliemic paralysis]

PMID- 12500145
TI  - [Progressive weakness of the ankle dorsiflexors related to 4q35 chromosome
      delection]

PMID- 12500147
TI  - [Foreword]

PMID- 12500146
TI  - [A few consequences of the war on cerebral vascular events in Sarajevo]

PMID- 12500148
TI  - [Hereditary Motor Neuronopathies]

PMID- 12500149
TI  - [Restless leg syndrome arousal: clinic, etiology and genetic perspectives]

PMID- 12500150
TI  - [Contribution of elecroneuromyography for the exploration of radiculopathy]

PMID- 12500151
TI  - [Alcoholic and nutritional neuropathies]

PMID- 12500152
TI  - [Contribution of MRI to the diagnosis of multiple system atrophy]

PMID- 12500153
TI  - Metaglip and Avandamet for type 2 diabetes.

PMID- 12500154
TI  - Dutasteride (Avodart) for benign prostatic hyperplasia.

PMID- 12500156
TI  - Memories and traces. From Jewish exilists' authoritarian personality research via
      Cloninger's psychobiology of personality traits to a neurobiological approach to
      conflict management.
AB  - Research on personality as a useful construct to understand people's behavior in
      conflict situations was traced over more than fifty years, and an attempt was
      made to add neurobiological parameters to psycho-socio-cultural approaches. As a
      starting point, scientists in exile have been called to mind who had been
      expelled from Nazi Germany for their Jewish origins. Among them were Adorno and
      Frenkel-Brunswik whose extensive studies on the authoritarian personality
      structure were quoted. In their work, personality was defined as a more or less
      enduring organisation of forces within the individual helping to determine
      responses in various situations, which is responsible for consistency in
      behavior. As a next step, Cloninger's psychobiology of personality traits was
      presented. In his personality concept, four temperamental traits (novelty
      seeking, harm avoidance, reward dependency and persistence) and three character
      dimensions are included. Temperamental traits are heritable, developmentally
      stable, emotionally based, uninfluenced by social learning, and linked to
      specific brain biological features. The temperaments have a certain
      neuroendocrinological feature which can be determined. Character dimensions
      develop in a stagelike process from infancy to adulthood and are influenced by
      temperament, social learning, genetic factors, and random life events.
      Personality is still considered a useful theoretical approach to conflict
      management research and practice. A neurobiological point of view seems to be a
      useful supplementation in addition to traditional psycho-socio-cultural
      approaches. Measuring biological compounds can supply the conflict manager with
      an additional tool of knowledge enhancing the ability to understand and
      anticipate conflict behavior.

PMID- 12500157
TI  - Late nocturnal sleep onset impairs a melatonin shower in young children.

PMID- 12500158
TI  - A casuistic rationale for the treatment of spastic and myocloni in a childhood
      neurodegenerative disease: neuronal ceroid lipofuscinosis of the type Jansky
      Bielschowsky.
AB  - GOAL: The casuistic of a child suffering from late infantile neuronal ceroid
      lipofuscinosis (NCL) of the type Jansky-Bielschowsky aims to provide a
      description of possible therapeutic options for the severe spastic and the
      debilitating myocloni that occur within the context of this disorder. Moreover,
      it also should include a discussion of potential indications for the application
      of delta 9-Tetrahydrocannabinol (THC) (Dronabinol, Marinol) in childhood.

PMID- 12500159
TI  - Cytoprotection by melatonin and growth hormone in early rat myocardial infarction
      as revealed by Feulgen DNA staining.
AB  - OBJECTIVE: To examine the cytoprotective effect of melatonin or recombinant human
      growth hormone (hGH) on the early phase of a running myocardial infarction in
      rats by using the Feulgen staining. METHODS: Rats were subjected to surgical
      ligature of the left coronary artery or its sham-operation and were studied 1.5 3
      h later. Melatonin was administered in the drinking water (100 microg/ml water)
      for 7 days before surgery. Recombinant hGH (2 IU/kg) was given ip at the time of
      surgery. Feulgen-stained histological cardiac sections were examined by light
      microscopy and image analysis. RESULTS: Infarcted rats receiving vehicle
      exhibited large, diffuse cardiac lesions with a marked positivity for Feulgen
      reaction. About 18 20% of the total area recorded became injured 1.5 or 3 h after
      infarction, respectively. Infarcted rats treated with melatonin or hGH, or the
      combination of both, and killed 3 h after surgery, showed cardiac sections with
      scattered lesions and only a few isolated injured muscle fibers. A similar
      effectiveness of melatonin and hGH, alone or in combination, to decrease injured
      area by 86 87% and the number of cardiac lesions by 75 80% was observed.
      CONCLUSION: A significant cytoprotective effect of melatonin or hGH is
      demonstrable in an early phase of myocardial infarction in rats.

PMID- 12500160
TI  - Non-sprouting angiogenesis in neurohypophysis after traumatic injury of the
      cerebral cortex. Electron-microscopic studies.
AB  - OBJECTIVES: Angiogenesis comprises two different mechanisms: endothelial
      sprouting and intussusceptive microvascular growth. The sprouting process is
      based on endothelial cell migration, proliferation and tube formation.
      Intussusceptive microvascular growth divides existing vessel lumens by formation
      and insertion of endothelial columns into the vessel lumen. The morphological
      features of microvessels of cerebral cortex and neurohypophysis were evaluated in
      a model of the cerebral traumatic injury. METHOD: The observations were conducted
      seven days after induction of cortical trauma. Traumatic injury was induced in
      the fronto-temporal region of cerebral cortex in general anesthesia with 20mg/kg
      ketamine hydrochloride. RESULTS: Seven days after traumatic brain injury in
      sections from cerebral cortex and neurohypophysis we can observe morphological
      features of angiogenesis. Endothelium of the cerebral cortex possesses high
      endotheliocytes tightly connected and enveloped by amorphous basement membrane
      like material. Transcapillary pillars tightly connected with neighbouring
      endothelial cells split the newly formed vessels and branching takes place. In
      neurohypophysis we can observe all stages of non-sprouting angiogenesis:
      proliferation endothelial cells on the inside mother vessel, splitting newly
      formed blood vessels by transcapillary pillars directed into the vessel lumen,
      maturation of endothelium and network formation. CONCLUSION: The mechanical
      injuries directly induced angiogenesis not only in cerebral cortex, but also in
      neurohypophysis. Our studies show that mechanism of angiogenesis is not the same
      as observed previously in neurohypophysis after focal cerebral ischemia
      (Neuroendocrinology Letters 2001; 22:87 92). This study indicates that mechanism
      of angiogenesis can depend on kind of induction.

PMID- 12500161
TI  - Effects of estradiol benzoate on the ultrastructure of the pinealocyte in the
      ovariectomized rat.
AB  - OBJECTIVE: The aim of this study was to examine the effects of ovariectomy and
      ovariectomy followed by estradiol benzoate administration on the ultrastructure
      of pinealocytes in female rat. DESIGN: For this purpose 15 female Wistar rats
      were used. Animals were divided into three groups. Group I and II were designated
      as sham-ovariectomized (control) and ovariectomized, respectively. Group III was
      ovariectomized and daily injected with estradiol benzoate for one month. At the
      end of the experiment, all animals were anesthetized with ketamine for fixation
      by vascular perfusion. Pineal glands of groups I, II and III were removed. All
      specimens were examined by electron microscopy. RESULTS: Ovariectomy caused an
      increase of lipid droplets, mitochondria and ribosomes. Rough endoplasmic
      reticulum was extensive in the cytoplasm. Estradiol administration to
      ovariectomized rats resulted in formation of less extensive lipid droplets,
      mitochondria and ribosomes compared to pinealocyte ultrastructure of both control
      and ovariectomized rats. Extensiveness of rough endoplasmic reticulum in the
      pinealocytes of estradiol-administrated rats was similar to that in controls.
      CONCLUSIONS: The results confirm relationship between the pineal gland and gonads
      in the rat and it has been suggested that estradiol benzoate reverses the
      ultrastructural changes, which indicate increased cell activation, occurring in
      the pinealocytes after ovariectomy.

PMID- 12500162
TI  - Effect of epitalon on interleukin-1beta signal transduction and the reaction of
      thymocyte blast transformation under stress.
AB  - OBJECTIVES: The aim of this research consisted in studying the effects of
      tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL
      1beta) signal transduction via sphingomyelin pathway in the cerebral cortex
      membranes of mice exposed to stresses exerting diverse effects upon humoral
      immune response. DESIGN AND SETTING: The experiments were performed on male
      (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were
      used: immune-stimulatory rotation stress and immune-suppressive combined stress
      (cooling followed by immobilization). The concomitant effect of Epitalon was
      determined according to its influence on thymocyte proliferation stimulated by
      concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of
      membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin
      signal transduction pathway, was assayed according to modified Rao and Spence's
      method (1976). RESULTS: The investigation demonstrated that Epitalon increased
      thymocyte proliferative activity, both enhanced under rotation stress and
      suppressed under combined one. It also increased IL-1beta concomitant effect.
      These findings corresponded to Epitalon effect on diverse stress-induced changes
      in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in
      the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory
      effect on the enzyme activity. CONCLUSIONS: The obtained results provided a
      conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta
      signal transduction via sphingomyelin pathway in the nerve tissue, as well as at
      the level of target thymocyte proliferation.

PMID- 12500163
TI  - The relationship between the daily profile of chosen biochemical markers of bone
      metabolism and melatonin and other hormone secretion in rats under physiological
      conditions.
AB  - BACKGROUND: The mechanism of generating and synchronizing daily rhythms of bone
      and mineral metabolism markers has not been entirely explained. Most studies
      indicate that LD cycle and/or feeding schedules provide important synchronizers
      of these rhythms. It seems that endogenous factors, including systemic and local
      hormones can be important in the mechanism of dependence of bone and mineral
      metabolism parameters rhythms on LD cycle and feeding schedule. OBJECTIVE: To
      assess the relationship between the daily profile of chosen biochemical
      parameters of bone and mineral metabolism (serum ALP, PICP, ICTP and iP and
      urinary excretion of HYP and total calcium) and daily secretion of MEL, GH/IGF-I
      axis activity and parathyroid, thyroid, adrenal cortex and gonads function in 48
      adult male rats. METHODS: Material for studies was collected every 3 hours within
      a day. Hormones, PICP and ICTP concentrations were determined with the use of RIA
      method and ALP, HYP, total calcium and iP values--spectrophotometrically.
      RESULTS: Existence of a negative correlation between daily oscillations of
      studied markers of osteogenesis (ALP and PICP) and daily profile of MEL and PTH
      secretion and positive with daily fluctuations of GH and IGF-I was shown.
      Moreover, ALP values correlated negatively with daily oscillations of CT.
      Concentrations of bone resorption markers (ICTP, HYP and total calcium)
      correlated negatively with daily fluctuations of MEL and positively with GH, IGF
      I and thyroid hormones. CONCLUSION: The present results suggest that
      physiological daily rhythmicity of PTH, MEL, GH, IGF-I and thyroid hormones most
      probably play an important role in regulating the daily rhythm of biochemical
      markers of bone metabolism.

PMID- 12500164
TI  - DDT in human milk and mental capacities in children at school age: an additional
      view on PISA 2000.
AB  - OBJECTIVES: To investigate a possible lasting impact of dichlorodiphenyl
      trichloroethane (DDT) exposure in neonatal life on mental capacities in later
      life. MATERIAL AND METHODS: Relationships were evaluated by correlation and
      regression analysis between total DDT concentrations in human breast milk in the
      years of birth (1984/1985) and measurements of mental capacities obtained in
      pupils of the PISA 2000 studies as well as percentages of backward children in
      Germany in 1994/95. RESULTS: Comparing total DDT levels in human milk during the
      years of birth (1984/85) evaluable for eleven PISA countries with assessed mental
      capacities of 15-year-old pupils of PISA International, a significant inverse
      correlation was found (p < 0.001), even after adjustment for socioeconomic
      statuses (p = 0.001). Furthermore, a significant inverse correlation (p < 0.001)
      was also obtained between the total DDT concentrations in human milk in 1984/85
      in ten foreign countries of three continents plus fourteen Federal States of
      Germany and the mental capacities of 15 year-old pupils of PISA International
      plus PISA National (Germany) 2000. Finally, a significant positive correlation
      was observed between total DDT contents in human milk in 1984/85 and the
      percentages of backward school children in 1994/95 in Federal States of Germany
      (p < 0.001). CONCLUSIONS: These data in association with additional experimental
      and epidemiological findings suggest that DDT is a "neuroendocrine disrupter" as
      well as a "functional teratogen" leading to harmful effects on brain development
      and mental capacities in later life. Thus, a neuroendocrine prophylaxis during
      critical developmental periods in early life as recommended by our group since
      many years appears to be most important for primary preventive medicine but even
      for "preventive pedagogics". The validity of these theses should be re-tested in
      future PISA studies.

PMID- 12500165
TI  - Mechanism of ghrelin-evoked glucagon secretion from the pancreas of diabetic
      rats.
AB  - OBJECTIVE: Ghrelin is a newly discovered peptide, which was first demonstrated in
      the epithelium of rat stomach. The purpose of the study was to examine the effect
      of ghrelin on glucagon secretion from pancreatic tissue fragments of normal and
      diabetic rats. METHODS: Diabetes was induced by streptozotocin (60 mg Kg body
      weight 1) given intraperitoneally. Four weeks after the onset of diabetes,
      pancreatic fragments of normal and diabetic rats were incubated with different
      concentrations (10 12 10 6 M) of ghrelin. Glucagon release was measured using
      radioimmunoassay technique. RESULTS: Ghrelin failed to stimulate or inhibit
      glucagon secretion from normal rat pancreas. However, it induced significant
      increases in glucagon secretion from pancreatic tissue fragments of diabetic
      rats. Either atropine (muscarinic cholinergic receptor antagonist) or propranolol
      (beta-adrenergic receptor antagonist) or yohimbine (alpha2-adrenergic receptor
      antagonist) or diltiazem (calcium channel antagonist) did not affect ghrelin
      glucagon interaction. Moreover, a combination of atropine, propranolol and
      yohimbine had no significant effect on the interaction of ghrelin with glucagon.
      CONCLUSION: The ghrelin-induced glucagon secretion in diabetic rats is not
      controlled via cholinergic or adrenergic pathways. In conclusion, it appears that
      the main target of ghrelin in the rat endocrine pancreas is not glucagon
      producing cells but rather insulin secreting cells which are more involve in
      weight gain and body growth.

PMID- 12500166
TI  - Effects of insulin and sulphonylureas on insulin-like growth factor-I levels in
      streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: Diabetes Mellitus is associated with decreased insulin-like growth
      factor-I (IGF-I) levels and also, poor growth in diabetes is related with low
      circulating levels of IGF-I. Insulin acts via an increase of IGF-I synthesis on
      growth. We studied the effects of insulin and sulphonylureas on serum IGF-I
      levels and aimed to evaluate the restoration of IGF-I in different therapeutic
      strategies. DESIGN AND SETTING: Thirty male rats were used in the study and
      diabetes was induced by a single intraperitoneal injection of streptozotocin (35
      mg/kg body weight). After confirmation of hyperglycemia, rats were divided into
      three groups. The first group was treated with insulin, and second group with
      glimepiride, third group was not treated (control group). IGF-I levels were
      measured at basal, after streptozotocin and at the end of the treatment period.
      RESULTS: Serum IGF-I levels were found to decrease from 577.2 ng/ml to 253.0
      ng/ml after streptozotocin (p<0.005). After 1 month, IGF-1 levels were found
      524.0 ng/ml in insulin group, 449.3 ng/ml in sulphonylurea group, and 313.1 ng/ml
      in control group. The increase in IGF-I was statistically significant in insulin
      group (p<0.005), and in sulphonylurea group (p<0.05), but it was not significant
      in control group (p>0.05). CONCLUSIONS: Serum IGF-I levels decrease in diabetes
      and insulin treatment restores IGF-I depletion significantly. And although less
      effective, treatment with glimepiride restores IGF-I levels significantly.

PMID- 12500167
TI  - Is there a gender difference of somatostatin-receptor density in the human brain?
AB  - Animal experiments and observations in human brains have convincingly shown that
      sexual differentiation not only concerns the genitalia but also the brain. This
      has been investigated also in the light of a possible explanation of a presumed
      biological aetiology of transsexuality. The volume of the central subdivision of
      the bed nucleus of the stria terminalis, a brain area that is essential for
      sexual behaviour, has been reported to be larger in men than in women.
      Additionally, the number of somatostatin expressing neurons in this region was
      shown to be higher in men than in women. As neuronal production of somatostatin
      is involved the idea is striking whether somatostatin-receptor density in the
      cortex of cerebral hemispheres might be related to gender identity. We
      investigated in vivo the density of somatostatin-receptors in selected regions of
      the human brain in both sexes by means of receptor scintigraphy. Basal ganglia
      tracer uptake of 111-In-Pentreotide was equally low in both genders at 0,80% +/
      0,26 (related to tracer uptake of the whole brain layer). Temporal cortex
      accumulated at 2,9% +/ 1,1 in men and at 2,3% +/ 0,76 in women. Frontal brain
      region had an uptake of 3,0% +/ 1,4 in male and of 2,5% +/ 1,3 in female. This
      shows a tendency in males for relatively augmented uptake indicating higher
      somatostatin receptor density in temporal and frontal cerebral cortex.

PMID- 12500169
TI  - Effect of superior cervical ganglionectomy on the ultrastructure of pinealocytes
      in the Djungarian hamster (Phodopus sungorus): quantitative study.
AB  - OBJECTIVES: Superior cervical ganglia are of crucial importance in regulating the
      secretion of the pineal hormone melatonin. Changes in pineal morphology have been
      observed in many mammalian species after sympathectomy. Therefore, we decided to
      investigate the ultrastructure of Djungarian hamster pinealocytes following
      superior cervical ganglionectomy. MATERIAL AND METHODS: Eight adult female
      Djungarian hamsters (Phodopus sungorus) were used in this study. The superior
      cervical ganglia were removed bilaterally in four animals, whereas the other four
      animals served as sham-operated controls. The pineal glands were removed four
      weeks after the operation and processed for electron microscopic study. The cross
      sectional areas of pinealocyte and its nucleus, and relative volume of
      mitochondria, Golgi apparatus, lysosomes, granular endoplasmic reticulum, and
      glycogen particles as well as the numbers of dense-core vesicles and "synaptic"
      ribbons were estimated using a digital analyzer connected on-line to IBM-PC
      computer. Statistical analysis of the data was performed using Student's t test
      and Snedecor F test. RESULTS: Significant reduction in the cross-sectional areas
      of the pinealocyte and its nucleus as well as in the relative volumes of
      mitochondria and glycogen particles was observed after superior cervical
      ganglionectomy in comparison with sham-operated controls. Sympathectomy resulted
      also in reduction of the number of dense-core vesicles. On the contrary 2,5 fold
      increase in the number of "synaptic" ribbons was observed in ganglionectomized
      animals in comparison to sham-operated controls. CONCLUSION: Deprivation of
      sympathetic innervation leads in Djungarian hamsters not only to suppression of
      melatonin synthesis and secretions but, as appears from our studies, induces also
      morphological changes suggesting lower metabolic and secretory activity of
      pinealocytes.

PMID- 12500170
TI  - The neuroendocrine phenotype, cellular plasticity, and the search for genetic
      switches: redefining the diffuse neuroendocrine system.
AB  - The term neuroendocrine has been used to define cells that secrete their products
      in a regulated manner, in response to a specific stimulus. The neuroendocrine
      system includes neurons and endocrine cells sharing a common phenotypic program
      characterized by the expression of markers such as neuropeptides, chromogranins,
      neuropeptide processing enzymes SPC2 and SPC3 (subtilase-like pro-protein
      convertases) or dense core secretory granules. Various theories such as the APUD
      (amine precursor uptake decarboxylation) concept, the diffuse neuroendocrine
      system (DNES) or the paraneuron concept have been put forth to classify
      neuroendocrine cells as a cohesive group. Neuroendocrine characteristics have
      been used as evidence of a common embryological origin for normal and neoplastic
      cells. However, it is now recognized that neuroendocrine characteristics can be
      observed in various cell types, such as immunocytes, that are not of a common
      embryological origin with either neurons or endocrine cells. We propose to
      redefine previous "neuroendocrine" concepts to include the notion that activation
      of specific genetic switches can lead to the expression of a partial or full
      neuroendocrine phenotype in a variety of cell types, including immune cells.

PMID- 12500171
TI  - Epitalon influences pineal secretion in stress-exposed rats in the daytime.
AB  - OBJECTIVES: The content of C-Fos protein was tested in rat pinealocytes in the
      norm and stress and in case of intranasal administration of Epitalon (Ala-Glu-Asp
      Gly), which regulated pineal secretion processes, presumably, via protooncogenes.
      SETTING: Intact and osmotic-stress-exposed rats were used for the
      immunohistochemical detection of C-Fos protein. All animals were intranasally
      administered with Epitalon, the last infusion made in two hours before the
      biopsy. Simultaneously, light microscopy of the pineal parenchyma was performed
      in all groups of animals. RESULTS: A slight but significant C-Fos increase was
      observed only in stress-exposed pinealocytes of rats after intranasal Epitalon
      infusions. C-Fos was irregularly distributed throughout pineal cells. In stress,
      the clusters of 5 10 cells containing C-Fos in their cytoplasm were detected. The
      dilation of capillaries and pericapillary space induced by an osmotic stress was
      partially reduced by the intranasal infusions of Epitalon. CONCLUSIONS:
      Tetrapeptide Epitalon is synthesised on the basis of the amino acid composition
      of pineal peptide extract Epithalamin. Epitalon modulates pineal secretion only
      under a stress impact but never in the norm. It prevents osmotic-stress-induced
      pathologic changes in the pineal parenchyma structure. Besides, the physiological
      activity of Epitalon seems to be mediated by the activation of protooncogenes in
      pinealocytes.

PMID- 12500172
TI  - The effect of hormonal factors on the hearing organ in women, after surgical
      castration. Preliminary report.
AB  - BACKGROUND: Estrogens have not only direct and beneficial effect on relaxation of
      the arteries increasing the blood flow in the blood vessels, but also their level
      of secretion has considerable effect on synthesis of acetylcholine a
      neurotransmitter indispensable for appropriate functioning of the hearing organ.
      The aim of this study is analysis of the effect of hormones on the hearing organ
      in women who underwent surgical castration. MATERIAL: The study included 40
      females, aged between 32 55 years who had undergone an operative treatment mainly
      because of uterine myoma. A group of 50 women aged between 32 50 years with
      appropriate hormone level comprised the control group. METHOD: Each woman
      investigated underwent the following examinations: gynaecological,
      otolaryngological and laboratory tests, such as: evaluation of levels of
      estradiol (E) and folliculin stimulating hormone (FSH). The assessment of hearing
      was carried out using tone and speech audiometry, tympanometry, test registration
      of auditory brain stem responses (ABR) and otoacoustic emissions (EOAE). The
      examinations mentioned above are performed in women as initial examinations
      before surgical treatment and as follow-up examinations 1, 3 and 12 months after
      the surgery. RESULTS: The results presented in this paper include initial
      examinations and follow-ups 3 months after the surgical treatment taking into
      consideration the correlation with the results of laboratory tests and the
      results obtained in the control group.

PMID- 12500173
TI  - Removal of dental amalgam and other metal alloys supported by antioxidant therapy
      alleviates symptoms and improves quality of life in patients with amalgam
      associated ill health.
AB  - OBJECTIVES: The purpose of this study was to evaluate treatment of patients
      suffering from chronic ill health with a multitude of symptoms associated with
      metal exposure from dental amalgam and other metal alloys. SETTING AND DESIGN: We
      included 796 patients in a retrospective study using a questionnaire about
      symptom changes, changes in quality of life as a consequence of treatment and
      assessment of care taking. METHODS: Treatment of the patients by removal of
      offending dental metals and concomitant antioxidant therapy was implemented
      according to the Uppsala model based on a close co-operation between physicians
      and dentists. RESULTS: More than 70% of the responders, remaining after exclusion
      of those who had not begun or completed removal, reported substantial recovery
      and increased quality of life. Comparison with similar studies showed accordance
      of the main results. Plasma concentrations of mercury before and after treatment
      supported the metal exposure to be causative for the ill health. MAIN FINDINGS:
      Treatment according to the Uppsala model proved to be adequate for more than 70%
      of the patients. Patients with a high probability to respond successfully to
      current therapy might be detected by symptom profiles before treatment.
      CONCLUSIONS: The hypothesis that metal exposure from dental amalgam can cause ill
      health in a susceptible part of the exposed population was supported. Further
      research is warranted to develop laboratory tests to support identification of
      the group of patients responding to current therapy as well as to find out causes
      of problems in the group with no or negative results.

PMID- 12500174
TI  - Presence of phosducin in the nuclei of bovine retinal cells.
AB  - PURPOSE: During the course of our investigations on cyclic nucleotide dependent
      phosphorylation of membrane proteins, we observed that phosducin was present in
      both the cytosolic and nuclear fractions. It has been suggested that phosducin
      might have a role in regulating transcription, but its presence in the nucleus
      has not been previously reported. We therefore attempted to purify nuclei from
      bovine retina and determine whether the purified preparation contained phosducin.
      Cyclic nucleotide-dependent phosphorylation of the protein was also investigated
      in the homogenate and subcellular fractions of bovine retina. METHODS: Freshly
      obtained bovine retinas were homogenized and fractionated in an isotonic buffer.
      The homogenate and subcellular fractions were subjected to phosphorylation in the
      presence of gamma-32P ATP and the presence and absence of cyclic GMP. The
      phosphorylated proteins were identified by 1- or 2-dimensional electrophoresis
      and autoradiography. Phosducin was detected in the fractions by western blotting.
      A nuclear preparation was obtained from the homogenate by sucrose gradient
      centrifugation, its purity was determined with a nuclear stain, and the presence
      and phosphorylation of phosducin was investigated as above. RESULTS: Phosducin
      was found in the cytosol, 100,000x g membrane fraction, as well as in the 120x g
      pellet of a fresh, isotonic retinal homogenate, but cyclic nucleotide-dependent
      phosphorylation of the protein was observed only in the cytosolic fraction.
      Western blotting on a highly purified nuclear fraction showed that phosducin was
      present in the nuclei. The protein could be phosphorylated in a cyclic GMP
      dependent fashion in a nuclear preparation permeabilized by freezing and thawing.
      CONCLUSIONS: It has been suggested that a C-terminal fragment of phosducin might
      be transported into the nucleus where it might have a role in the regulation of
      transcription. Phosducin localization in the nucleus was shown in COS cells
      cotransfected with genes of phosducin and a transcription factor. However, the
      presence of phosducin in the nuclei of retina has not been demonstrated hitherto.
      The present results show that phosducin is present in the nuclei in bovine
      retina. It could be phosphorylated in the nuclei in a cyclic GMP-dependent
      fashion. These results support a possible role for phosducin in the regulation of
      transcription.

PMID- 12500175
TI  - Quantification of chick lens alphaA- and delta-crystallins in experimentally
      induced ametropia.
AB  - PURPOSE: The role of the lens in experimentally induced ametropia is not known. A
      recent study of the chick lens demonstrated optical quality deterioration with
      the induction of refractive errors, without alteration in lens morphology, size
      or shape. A change in lens gradient of refractive index (which is dependent on
      alpha-, beta-, and delta-crystallin concentration and arrangement), could
      underlie this observation. The purpose of this work was to quantify the
      concentrations of alphaA- and delta-crystallin in lenses from chick eyes with
      induced high myopia or hyperopia. METHODS: White Leghorn chicks were unilaterally
      fitted on the day of hatching either with translucent plastic goggles to induce
      form-deprivation myopia (n=21) or with +15 D defocus goggles to induce hyperopia
      (n=14). The ungoggled contralateral eyes were used as controls. The chicks were
      refracted twice, once on the day of hatching and again seven days later, using
      streak retinoscopy. On day 7 chicks were sacrificed, lenses decapsulated, and
      soluble proteins were isolated. Western blot assays were optimized and used to
      assess crystallin concentration. RESULTS: Analysis revealed no significant
      difference in alphaA- or delta-crystallin concentration in lenses from eyes
      induced with form-deprivation myopia and hyperopia as compared to their
      respective control eyes. Analysis of the difference in medians of delta
      crystallin between the control and treated groups of the myopia and hyperopia
      experiments revealed significance (p=0.030). CONCLUSIONS: This study suggests
      that with the induction of ametropia, the increased lens spherical aberration
      previously noted is not due to a change in the absolute concentration of lens
      alphaA- or delta-crystallin. However, results suggest that the myopic and
      hyperopic treatments had different effects on lens delta-crystallin
      concentration. Further investigation is necessary to expand the current knowledge
      of the role played by the lens in experimental ametropia.

PMID- 12500176
TI  - HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit
      model of PVR.
AB  - PURPOSE: To understand molecular events that lead to retinal pigment epithelial
      (RPE) cell proliferation and migration during the early phases of proliferative
      vitreoretinopathy (PVR) in a rabbit model. METHODS: Retinal holes were created
      and interleukin-1beta(IL-1beta) was injected intravitreally. Eyes were examined
      by indirect ophthalmoscopy and eyecup pieces containing retinal holes were
      analyzed at different times after the surgery up to 4 weeks. RPE proliferation
      and migration were examined by immunohistochemistry. Tyrosine phosphorylation of
      extracellular signal regulated kinase (ERK) and hepatocyte growth factor receptor
      (HGFR or c-met) was determined by immunoprecipitation and western blot analysis.
      Tyrosine phosphorylation of c-met and morphological studies was performed on
      vitreous treated ARPE-19 cells. Expression of c-jun was determined by Northern
      blot analysis. Matrix metalloproteinase (MMP) content in vitreous was assessed by
      zymography. RESULTS: Indirect ophthalmoscopy identified formation of epiretinal
      membrane and immunohistochemistry identified proliferative and migratory RPE and
      other cells in the posterior segment containing retinal holes at 4 weeks post
      surgery. Tyrosine phosphorylation of ERK and c-met occurred in this segment
      within 30 min of surgery. ARPE-19 cells treated with vitreous from the 24 h post
      surgical eyes, but not with control vitreous or IL-1beta, showed morphological
      changes and tyrosine phosphorylation of c-met. Northern blot analysis in this
      segment identified upregulation of c-jun within 30 min of surgery and the
      expression peaked at 72 h. Zymographic analysis of vitreous identified MMP-9 in
      12-72 h post-surgery. CONCLUSIONS: These data suggest that the presence of
      retinal holes and IL-1beta may lead to activation of HGF, mitogen activated
      protein kinases (MAPK), c-jun and extracellular matrix remodeling, resulting in
      proliferative and migratory cells in the wounded retina.

PMID- 12500177
TI  - MAP kinase and beta-catenin signaling in HGF induced RPE migration.
AB  - PURPOSE: Hepatocyte growth factor (HGF) has been implicated in retinal pigment
      epithelial (RPE) cell proliferation and migration that occurs in proliferative
      retinal diseases such as proliferative vitreoretinopathy (PVR). The aim of this
      study is to investigate HGF induced signaling pathways that lead to RPE cell
      migration. METHODS: Localization of beta-catenin was determined by
      immunofluorescence. HGF induced migration of ARPE-19 cells was studied using a
      quantitative migration assay after wounding in the presence of a DNA polymerase
      inhibitor, and in the presence or absence of a mitogen activated protein kinase
      (MAP kinase) kinase inhibitor. C-jun expression was determined by semi
      quantitative RT-PCR and by Northern blot analysis. P42/p44 MAP kinase activity
      was determined by western blot and by an immunoprecipitation kinase assay.
      Tyrosine phosphorylation of the HGF receptor (HGFR or c-met) and beta-catenin was
      determined by immunoprecipitation and western blot analysis. Transactivation
      activity of beta-catenin was determined by luciferase reporter gene analysis.
      RESULTS: Beta-catenin and E-cadherin were co-localized on the basal surface of
      the RPE in vivo. Diffusion of the cell surface-localized beta-catenin occurs in
      migratory cells in vitro in the presence of HGF. HGF induced a MAP kinase
      dependent ARPE-19 cell migration, which is accompanied with a transient increase
      of c-jun expression and concomitant increases of MAP kinase activity, tyrosine
      phosphorylation of HGFR and beta-catenin, increased cytosolic levels of beta
      catenin, and transactivation activity of beta-catenin. Tyrosine phosphorylation
      of HGFR and beta-catenin occurs in the primary or passaged RPE cultures or
      proliferative ARPE-19 cells, but not freshly isolated RPE or differentiated ARPE
      19 cells. CONCLUSIONS: This study defines the signal transduction pathways
      activated by HGF in RPE cells, leading to an increase in the MAP kinase activity
      and free pool of beta-catenin, and changes in gene expression. These findings are
      consistent with the hypothesis that both beta-catenin and MAP kinases are
      components of the HGF induced RPE migration that occurs in proliferative retinal
      diseases.

PMID- 12500180
TI  - Hepatitis C research.

PMID- 12500181
TI  - Vascular mediators in the injured liver.

PMID- 12500182
TI  - Clinical need for antidiuretic hormone antagonists in cirrhosis.

PMID- 12500183
TI  - Adoptive transfer of immunity to HBV through liver graft: does it prevent HBV
      recurrence?

PMID- 12500184
TI  - Influence of hepatitis B virus genotypes on the progression of chronic type B
      liver disease.
AB  - To investigate the hepatitis B virus (HBV) genotype-related differences in the
      progression of liver disease, 585 patients with chronic HBV infection including
      258 with histologically verified chronic liver disease (CLD) and 74 with
      hepatocellular carcinoma (HCC) were examined. The mean ages of both patients with
      advanced fibrosis (F3 or F4) and with HCC were significantly older in genotype B
      than in genotype C patients (P =.018, P =.024, respectively). Both the hepatitis
      B e antigen (HBeAg) negativity rate at biopsy and the cumulative HBe
      seroconversion rate in patients with CLD were significantly higher in genotype B
      patients than genotype C patients (P <.01, P =.022, respectively). Multivariate
      analysis revealed that genotype B, presence of precore mutation, high ALT levels,
      and severe histologic activity were independent factors for HBe seroconversion.
      Among all the biopsy-proven CLD patients, the ratio of patients with advanced
      fibrosis in genotype B was significantly lower than that in genotype C (4/30 vs.
      74/224, respectively; P =.034). This difference was more remarkable in younger
      patients (< or =45 years; 1/25 vs. 47/180, respectively; P =.020), and there was
      no difference in older patients (>45 years). The distribution of each genotype
      between CLD and HCC was very similar (B and C: 11.2% and 87.0% vs. 10.8% and
      89.2%, respectively). In conclusion, our results suggest that, although the
      patients with genotype B experience earlier HBe seroconversion, slower
      progression of liver fibrosis, and slower development of HCC, the life-long risk
      of progression to advanced fibrosis and development of HCC may not differ among
      genotypes B- and C-related chronic liver disease.

PMID- 12500186
TI  - Development of antibody to hepatitis B surface antigen after liver
      transplantation for chronic hepatitis B.
AB  - Patients with chronic hepatitis B virus (HBV) infection have a defective HBV
      specific immune response, and the spontaneous development of antibody against
      hepatitis B surface antigen (anti-HBs) after liver transplantation has not been
      observed. We report the spontaneous production of anti-HBs in 21 of 50 (42%)
      patients receiving lamivudine monoprophylaxis after liver transplantation.
      Seroconversion to anti-HBs status (>10 mIU/mL) was found at a median of 8 days
      (range, 1 to 43 days) after transplantation. In each case, serial serum samples
      showed a >100% increase in antibody titer as compared with that of day 7 after
      transplantation in the absence of any blood product transfusion. The anti-HBs
      titer increased to a maximum within 3 months, and the peak titer was <100 mIU/mL
      in 10 patients, 100 to 1000 mIU/mL in 5 patients, and >1,000 mIU/mL in 6
      patients. In 12 patients, anti-HBs disappeared from serum at a median of 201 days
      (range, 24 to 414 days), whereas the other 9 patients remained positive for anti
      HBs at a median of 221 days (range, 94 to 1,025 days) after transplantation.
      Patients in whom anti-HBs in serum developed had a more rapid clearance of serum
      hepatitis B surface antigen (HBsAg) (log rank test, P =.011). Using logistic
      regression analysis, the only predictor of anti-HBs production was an HBV-immune
      donor (odds ratio, 18.9; 95% confidence interval, 3.2 to 112.4; P =.001). In
      conclusion, patients who undergo liver transplantation for chronic hepatitis B
      using lamivudine prophylaxis may develop anti-HBs spontaneously. The antibody is
      likely to be of donor origin, suggesting the possibility of adoptive immunity
      transfer through a liver graft.

PMID- 12500185
TI  - Effect of the G1896A precore mutation on drug sensitivity and replication yield
      of lamivudine-resistant HBV in vitro.
AB  - Hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) is frequently
      caused by a mutation (G1896A) in the hepatitis B virus (HBV) precore (PC) reading
      frame that creates a stop codon, causing premature termination of the PC protein.
      During lamivudine treatment, drug resistance develops at a similar rate in HBeAg
      positive and HBeAg negative CHB. Lamivudine-resistant HBV mutants have been shown
      to replicate inefficiently in vitro in the absence of PC mutations, but it is
      unknown whether the presence of PC mutations affects replication efficiency or
      antiviral sensitivity. This study utilized the recombinant HBV baculovirus system
      to address these issues. HBV baculoviruses encoding the G1896A PC stop codon
      mutation were generated in wild-type (WT) and lamivudine-resistant (rtM204I and
      rtL180M + rtM204V) backgrounds, resulting in a panel of 6 related recombinant
      baculoviruses. In vitro assays were performed to compare the sensitivities of the
      PC mutant viruses with lamivudine and adefovir and to compare relative
      replication yields. The PC mutation did not significantly affect sensitivities to
      either adefovir or lamivudine. WT HBV and PC mutant HBV showed similar
      replication yields, whereas the replication yields of the lamivudine-resistant
      mutants were greatly reduced in HBeAg positive HBVs, confirming previous
      observations. However, the presence of the PC mutation was found to compensate
      for the replication deficiency in each of the lamivudine-resistant mutants,
      increasing the replication yields of each virus. In conclusion, the PC stop codon
      mutation appears to increase the replication efficacy of lamivudine-resistant
      virus but does not affect in vitro drug sensitivity.

PMID- 12500187
TI  - Cost-effectiveness of hepatitis A vaccination in children, adolescents, and
      adults.
AB  - Hepatitis A is a major public health problem in the United States and other
      developed countries, largely because decreased natural immunity allows for
      increased susceptibility. To evaluate the cost-effectiveness of routine
      vaccination of children, adolescents, and certain high-risk adults against
      hepatitis A, economic analyses of hepatitis A vaccination were identified through
      searches of MEDLINE, EMBASE, and BIOSIS (February, 1992, to December, 2001) for
      studies, reviews, editorials, and letters from peer-reviewed journals published
      in English, French, German, Italian, or Spanish. Experts were also contacted.
      Articles conforming to accepted standards of quality for health-economic studies
      were used to compile data on vaccination of children, and results were
      synthesized in a narrative review. This review of economic analyses of vaccine
      use in several developed countries shows cost-effectiveness comparable with that
      of other vaccines in children and within accepted boundaries for adolescents and
      high-risk adults.

PMID- 12500188
TI  - Hepatitis C virus-like particles combined with novel adjuvant systems enhance
      virus-specific immune responses.
AB  - We have previously described the generation of hepatitis C virus-like particles
      (HCV-LPs) in insect cells and shown that immunization with HCV-LPs elicited both
      humoral and cellular immune responses in mice. To further characterize the HCV
      LPs as a vaccine candidate, we evaluated the effects of adjuvant AS01B
      (monophosphoryl lipid A [MPL] and QS21), CpG 10105, and the combination of the 2
      adjuvants on the immunogenicity of HCV-LPs in AAD mice (transgenic for HLA-A2.1).
      All HCV-LP-immunized mice (with or without adjuvant) developed high titers of
      anti-HCV E1/E2 antibodies after 4 injections intramuscularly. However, antibody
      titers in mice immunized with HCV-LP plus AS01B, plus CpG 10105, or plus the
      combination of AS01B and CpG 10105 were 4, 3, and 10 times higher, respectively,
      than that of HCV-LP alone. Isotype analysis of the induced anti-envelope
      antibodies showed that HCV-LP alone induced a predominant immunoglobulin (Ig) G1
      response. In contrast, when the 2 adjuvants AS01B and CpG 10105 were combined,
      the response became predominantly IgG2a whereas HCV-LP plus AS01B or CpG 10105
      gave a mixed IgG1 and IgG2a response, indicating that AS01B and CpG 10105 promote
      a more T-helper type 1 (Th1) response and that combining the 2 adjuvants results
      in an additive or synergistic interaction. These observations were further
      confirmed by the results of CD4(+) enzyme-linked immunospot assay for interferon
      (IFN)-gamma and interleukin (IL)-4 and intracellular cytokine staining of IFN
      gamma producing CD8(+) cells. In conclusion, HCV-LP is a promising vaccine
      candidate against HCV infection and the adjuvants used are potent immune
      enhancers for this approach.

PMID- 12500189
TI  - Spontaneous viral clearance in patients with acute hepatitis C can be predicted
      by repeated measurements of serum viral load.
AB  - Early interferon (IFN) therapy prevents viral persistence in acute hepatitis C,
      but in view of the resulting costs and morbidity patients who really need therapy
      have to be identified. Twelve consecutive patients with acute hepatitis C (9
      women, 3 men, mean age: 39.5 +/- 18.8 y, genotype 1: 7, genotype 3a: 3, 2 could
      not be genotyped) were studied. The sources of infection were medical procedures
      in 6, sexual transmission in 3, and intravenous drug abuse in 3 patients. Viral
      load was measured by Cobas Amplicor HCV Monitor v2.0 (Roche Diagnostic Systems,
      Branchburg, NY). The time from infection to clinical symptoms was 43.3 +/- 8.6
      (mean +/- SD) days. Eight patients cleared hepatitis C virus (HCV) spontaneously
      and remained HCV-RNA negative with a follow-up of 9.0 +/- 3.9 months. In these
      patients viral load declined fast and continuously. The time from exposure to HCV
      RNA negativity was 77.4 +/- 25.3 and from the first symptoms was 34.7 +/- 22.1
      days. In 4 patients HCV-RNA levels remained high or even increased. Two of them
      became sustained responders to treatment initiated after a 6-week observation
      period. The 2 remaining patients were not treated (one because of
      contraindications for IFN, the other declined therapy) and are still HCV-RNA
      positive. In conclusion, patients with acute icteric hepatitis C have a high rate
      of spontaneous viral clearance within the first month after the onset of
      symptoms. IFN therapy appears only needed in patients who fail to clear the virus
      within 35 days after onset of symptoms. By this approach, IFN therapy was not
      necessary in two thirds of patients with acute hepatitis C.

PMID- 12500190
TI  - Interleukin-1beta gene polymorphisms associated with hepatocellular carcinoma in
      hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a major risk factor for developing
      hepatocellular carcinoma (HCC), a life-threatening sequel. However, the factors
      that affect disease progression to HCC have not been thoroughly elucidated.
      Genetic polymorphisms in proinflammatory cytokines, the interleukin 1 (IL-1)
      family (IL-1beta and IL-1ra) and tumor necrosis factor-alpha (TNF-alpha), were
      studied in 274 Japanese patients with chronic HCV infection and 55 healthy
      individuals using standard polymerase chain reaction-based genotyping techniques.
      The association between these polymorphisms and disease status was evaluated
      while controlling for confounding clinical variables. The proportion of patients
      with HCC in the IL-1beta-31 T/T (55%, odds ratio to C/C was 2.63, P =.009)
      genotype was higher than in the T/C (44%, odds ratio to C/C was 1.64, P =.149)
      and C/C genotypes (35%). The IL-1beta-31 and -511 loci were in near complete
      linkage disequilibrium, and the IL-1beta-511/-31 haplotype C-T was significantly
      associated with the presence of HCC (odds ratio of 1.51, P =.02). Polymorphisms
      in the TNF-alpha gene were not associated with disease. A multivariate analysis
      revealed that the IL-1beta-31 T/T genotype, alpha-fetoprotein >20 microg/L,
      presence of cirrhosis, male sex, and age >60 years were associated with the
      presence of HCC at odds ratios of 3.73 (T/T vs. C/C), 4.12, 4.03, 3.89, and 3.27,
      respectively. In conclusion, the IL-1beta-31 genotype T/T or the IL-1beta-511/-31
      haplotype C-T is associated with the presence of HCC in Japanese patients with
      chronic HCV infection.

PMID- 12500191
TI  - Nucleolar hypertrophy correlates with hepatocellular carcinoma development in
      cirrhosis due to HBV infection.
AB  - Patients with cirrhosis are at significant risk for hepatocellular carcinoma
      (HCC). The aim of the present study was to evaluate the relationship between the
      percentage of hepatocytes showing nucleolar hypertrophy and the development of
      HCC in cirrhosis of different causes. A total of 111 cirrhotic patients were
      studied, with a mean follow-up period of 83.3 months. Histologic sections from
      liver biopsy specimens were silver stained for selective visualization of the
      nucleolus; the nucleolar area was measured by image cytometry. Nucleoli with a
      size of 7 microm(2) or greater were considered to be hypertrophic. The nucleolar
      index was obtained by calculating the percentage of hepatocytes disclosing a
      nucleolar area of 7 microm(2) or greater. During the observation time, HCC was
      diagnosed in 39 of 111 patients. The incidence rate of HCC was greater in
      patients with nucleolar indexes of 2.5 or greater than in patients with nucleolar
      indexes of less than 2.5 (16.49%/y vs. 3.41%/y, respectively; P <.0001). The
      capacity of the nucleolar index to predict HCC development was separately tested
      in groups of patients divided by etiology, and it was found to be particularly
      relevant in hepatitis B virus (HBV)-related cirrhosis (P =.0006). Among patients
      with hepatitis C virus (HCV) infection, high nucleolar-index values were
      associated with a greater risk for HCC development, but the difference in the
      incidence rate of HCC between groups with a nucleolar index of 2.5 or greater and
      less than 2.5 was not statistically significant (P =.0944). In conclusion, our
      results have shown that high percentages of hepatocytes showing nucleolar
      hypertrophy significantly predict HCC development in patients with HBV infection,
      whereas their predictive value in HCV-related cirrhosis seems to be lower.

PMID- 12500192
TI  - Triiodothyronine enhances the regenerative capacity of the liver following
      partial hepatectomy.
AB  - This study investigates the effects of administering a primary mitogen,
      triiodothyronine (T(3)), at the time of 70% partial hepatectomy (PH) in the rat,
      thus combining the 2 distinct pathways of liver growth: direct hyperplasia and
      compensatory regeneration. T(3) enhances the proliferative response of
      hepatocytes within the liver following PH. Flash bromodeoxyuridine (BrdU)
      labeling showed a cell proliferation index 24 hours after PH alone of 26.5% +/-
      2.8%; when T(3) was administered at PH, it increased to 39.5% +/- 5.0% (P <.01
      compared with PH alone). Continuous BrdU labeling performed every 6 hours between
      15 and 72 hours following surgery showed an index of 84.0% +/- 4.0% when T(3) was
      administered at PH compared with 71.0% +/- 4.0% with PH alone (P <.01 compared
      with PH alone). This increase in cell proliferation resulted in a larger liver
      mass at 4 days in rats receiving T(3) at PH compared with PH alone (P <.05
      compared with PH alone). The difference in liver mass was matched with
      corresponding increases in total DNA and total protein levels as well as cell
      division, as confirmed by the frequent demonstration of twin daughter cells on
      histology. In conclusion, this study shows that a single dose of T(3) enhances
      the regenerative capacity of the liver following PH. The ability to enhance cell
      proliferation during compensatory hyperplasia following PH could be
      therapeutically valuable if applicable to humans.

PMID- 12500193
TI  - Activated stellate cells express the TRAIL receptor-2/death receptor-5 and
      undergo TRAIL-mediated apoptosis.
AB  - Apoptosis has emerged as an important mechanism to reduce numbers of activated
      stellate cells during the resolution phase of hepatic fibrosis. These
      observations suggest that activated stellate cells may be more susceptible to
      apoptotic stimuli than their quiescent counterparts. Because other activated cell
      types are more sensitive than their quiescent phenotypes to apoptosis by tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL), we examined the
      expression of TRAIL death receptors (DRs) and susceptibility to TRAIL
      cytotoxicity in stellate cells undergoing progressive activation. A spontaneously
      immortalized human stellate cell line, LX-2, was analyzed during 14 days of
      progressive activation following plating, during which time alpha-smooth muscle
      actin (alpha-SMA) and a beta-crystallin (markers of stellate cell activation)
      messenger RNA (mRNA) increased 7-fold and 5-fold, respectively. During this same
      interval, TRAIL-R1/DR4 and TRAIL-R2/DR5 mRNA expression increased 18-fold and
      17.6-fold, although TRAIL-R2/DR5 expression was quantitatively 103-fold greater
      than TRAIL-R1/DR4; parallel changes occurred in TRAIL/DR5 protein expression and
      cellular susceptibility to TRAIL-mediated apoptosis. Similar findings were
      observed in primary murine stellate cells undergoing activation on a plastic
      surface. In conclusion, stellate cells show activation-dependent TRAIL-R2/DR5
      expression and TRAIL-mediated apoptosis. Because TRAIL-R2/DR5 is not expressed by
      hepatocytes, TRAIL/DR5 agonists may be useful in reducing fibrosis by inducing
      stellate cell apoptosis.

PMID- 12500194
TI  - Cytochrome P450 2E1 responsiveness in the promoter of glutamate-cysteine ligase
      catalytic subunit.
AB  - Previous studies have shown cytochrome P450 2E1 (CYP2E1)-dependent
      transcriptional up-regulation of glutamate-cysteine ligase (GCL). To identify
      sequences mediating constitutive and induced expression of the catalytic subunit
      of GCL (GCLC), a series of deletion mutants from the 5'-flanking region (-3,802
      to +465) were transfected into control (C34) and CYP2E1-overexpressing (E47)
      HepG2 cells. Increased luciferase expression, both basal (2- to 3-fold) and
      following exposure to ethanol, arachidonic acid (AA), or AA plus iron, was
      detected in E47 cells with the full-length but not shorter reporter vectors.
      Basal induction was blocked by CYP2E1 inhibitors and catalase. Basal and
      inducible luciferase expression in E47 cells was blunted by the full-length
      construct mutated in the ARE4 site. Catalase and diallyl sulfide prevented basal
      and AA-induced messenger RNA (mRNA) levels of GCLC and the modulatory subunit of
      GCL (GCLM). Preincubation with low doses of AA increased glutathione (GSH) levels
      as well as GCLC and GCLM mRNAs, and this protected against H(2)O(2) and menadione
      toxicity. Primary hepatocytes from pyrazole-injected rats with high levels of
      CYP2E1 showed an increase in GSH levels as well as GCLC and GCLM mRNAs compared
      with saline controls, and this was prevented by diallyl sulfide. In conclusion,
      redox-sensitive elements directing constitutive and induced expression of the
      GCLC in CYP2E1-expressing cells are present in the ARE4 distal portion of the 5'
      flanking region, between positions -3,802 and -2,752, perhaps a reflection of
      metabolic adaptation to CYP2E1-generated oxidative stress.

PMID- 12500195
TI  - Foxf1 +/- mice exhibit defective stellate cell activation and abnormal liver
      regeneration following CCl4 injury.
AB  - Previous studies have shown that haploinsufficiency of the splanchnic and septum
      transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects
      in lung and gallbladder development and that Foxf1 heterozygous (+/-) mice
      exhibited defective lung repair in response to injury. In this study, we show
      that Foxf1 is expressed in hepatic stellate cells in developing and adult liver,
      suggesting that a subset of stellate cells originates from septum transversum
      mesenchyme during mouse embryonic development. Because liver regeneration
      requires a transient differentiation of stellate cells into myofibroblasts, which
      secrete type I collagen into the extracellular matrix, we examined Foxf1 +/-
      liver repair following carbon tetrachloride injury, a known model for stellate
      cell activation. We found that regenerating Foxf1 +/- liver exhibited defective
      stellate cell activation following CCl(4) liver injury, which was associated with
      diminished induction of type I collagen, alpha-smooth muscle actin, and Notch-2
      protein and resulted in severe hepatic apoptosis despite normal cellular
      proliferation rates. Furthermore, regenerating Foxf1 +/- livers exhibited
      decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of
      monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated
      expression of transforming growth factor beta1. In conclusion, Foxf1 +/- mice
      exhibited abnormal liver repair, diminished activation of hepatic stellate cells,
      and increased pericentral hepatic apoptosis following CCl(4) injury.

PMID- 12500196
TI  - Low-dose TNF-alpha protects against hepatic ischemia-reperfusion injury in mice:
      implications for preconditioning.
AB  - Tumor necrosis factor alpha (TNF-alpha) is implicated in the pathogenesis of
      hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the
      cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR)
      liver injury and is associated with activation of nuclear factor kappaB (NF
      kappaB) and cell cycle entry. We examined the pattern of TNF-alpha release during
      hepatic IR in the presence or absence of ischemic preconditioning, and we tested
      whether a single low-dose injection of TNF could mimic the biologic effects of
      ischemic preconditioning. In naive mice, hepatic and plasma levels of TNF-alpha
      rose during hepatic ischemia, reaching high levels after 90 minutes; values
      remained elevated during reperfusion until 44 hours. Following the ischemic
      preconditioning stimulus, there was an early rise in hepatic and serum TNF-alpha
      levels, but, during a second prolonged ischemic interval peak, TNF-alpha values
      were lower than in naive mice and declined to negligible levels by 2 hours
      reperfusion. An injection with 1 microg or 5 microg/kg body weight TNF-alpha 30
      minutes prior to hepatic IR substantially reduced liver injury determined by
      liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic
      preconditioning, TNF-alpha pretreatment activated NF-kappaB DNA binding, STAT3,
      cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry,
      determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte
      nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be
      simulated by TNF-alpha injection, which has identical downstream effects on cell
      cycle entry. We propose that transient increases in TNF-alpha levels may
      substitute for, as well as, mediate the hepatoprotective effects of ischemic
      preconditioning against hepatic IR injury.

PMID- 12500197
TI  - Dominant negative MORT1/FADD rescues mice from CD95 and TNF-induced liver
      failure.
AB  - Derangement of the apoptotic program is considered an important cause of liver
      disease. It became clear that receptor-mediated apoptosis is of specific interest
      in this context, and CD95 and CD120a, both members of the tumor necrosis factor
      (TNF) receptor superfamily, are the most prominent cell death receptors involved.
      The death signal is induced upon ligand binding by recruitment of caspases via
      the adapter molecule MORT1/FADD to the receptor and their subsequent activation.
      To investigate the role of MORT1/FADD in hepatocyte apoptosis, we generated
      transgenic mice expressing liver-specific dominant negative mutant. Mice looked
      grossly normal; breeding and liver development were not different compared with
      wild-type littermates. Expression of the transgene completely protected animals
      from liver failure induced by the anti-Fas antibody Jo2, whereas control animals
      died as expected 3 to 6 hours after i.p. injection of 15 microg antibody from
      acute hemorrhagic liver failure. Histology demonstrated only moderate
      inflammatory changes in the transgenic animals, whereas severe hemorrhagic
      hepatitis was observed in controls. Similar results were obtained in a model of
      TNF-mediated liver failure, in which transgenic animals survived significantly
      better than wild-type animals. In conclusion, our experiments provide evidence
      that MORT1/FADD is indispensable for Fas and TNF-mediated hepatic injury. This is
      not only of great importance for targeting future therapies for liver disease but
      might also serve as an intriguing model to study other causes of liver injury.

PMID- 12500198
TI  - Hydrogen peroxide overproduction in megamitochondria of troglitazone-treated
      human hepatocytes.
AB  - Troglitazone has been withdrawn from therapeutic options for diabetes mellitus
      because of its severe hepatocyte toxicity of unknown pathogenesis. The aim of the
      present study was to assess both morphologic and functional alterations in the
      mitochondria of troglitazone-treated hepatocytes. A polarized human hepatocyte
      cell line, OUMS-29, was used in this study. The mitochondrial volume and the
      mitochondrial transmembrane potential (DeltaPsi(m)) were examined using flow
      cytometry with nonylacridine orange (NAO) and rhodamine-123, respectively. An
      ultrastructural examination of the troglitazone-treated OUMS-29 cells was
      performed using transmission electron microscopy (TEM). Reactive oxygen species
      (ROS) production was assessed using flow cytometry with dihydroethidium and 2',7'
      dichlorodihydrofluorescein diacetate. A significant increase in the mitochondrial
      volume of the troglitazone-treated cells was found by the NAO analysis, in
      comparison with pioglitazone-treated and ciglitazone-treated cells. The increase
      in volume was due to a marked enlargement in the mitochondria. The markedly
      enlarged mitochondria with intramitochondrial electron-dense deposits were
      confirmed on TEM, which showed myelin-like structures, indicating degraded
      membrane constituents. The troglitazone-treated cells showed a significant
      decline in the DeltaPsi(m) per unit mitochondrial volume but resulted in no clear
      cell death. ROS analysis revealed a significant production of hydrogen peroxide
      in the troglitazone-treated hepatocytes. This production was attenuated using an
      antioxidant, N-acetyl-L-cysteine. In conclusion, troglitazone caused
      overproduction of hydrogen peroxide, which deteriorated both mitochondrial
      membrane structures and mitochondrial function, leading to a possible priming for
      the severe hepatocyte toxicity.

PMID- 12500199
TI  - Characterization of cell types during rat liver development.
AB  - Hepatic stem cells have been identified in adult liver. Recently, the origin of
      hepatic progenitors and hepatocytes from bone marrow was demonstrated.
      Hematopoietic and hepatic stem cells share the markers CD 34, c-kit, and Thy1.
      Little is known about liver stem cells during liver development. In this study,
      we investigated the potential stem cell marker Thy1 and hepatocytic marker CK-18
      during liver development to identify putative fetal liver stem cell candidates.
      Livers were harvested from embryonic and fetal day (ED) 16, ED 18, ED 20, and
      neonatal ED 22 stage rat fetuses from Sprague-Dawley rats. Fetal livers were
      digested by collagenase-DNAse solution and purified by percoll centrifugation.
      Magnetic cell sorting (MACS) depletion of fetal liver cells was performed using
      OX43 and OX44 antibodies. Cells were characterized by immunocytochemistry for
      Thy1, CK-18, and proliferating cell antigen Ki-67 and double labeling for Thy1
      and CK-18. Thy1 expression was found at all stages of liver development before
      and after MACS in immunocytochemistry. Thy1 positive cells were enriched after
      MACS only in early developmental stages. An enrichment of CK-18 positive cells
      was found after MACS at all developmental stages. Cells coexpressing Thy1 and CK
      18 were identified by double labeling of fetal liver cell isolates. In
      conclusion, hepatic progenitor cells (CK-18 positive) in fetal rat liver express
      Thy1. Other progenitors express only CK-18. This indicates the coexistence of
      different hepatic cell compartments. Isolation and further characterization of
      such cells is needed to demonstrate their biologic properties.

PMID- 12500200
TI  - An optimal therapeutic expression level is crucial for suicide gene therapy for
      hepatic metastatic cancer in mice.
AB  - The most serious problem in current gene therapy is discrepancies between
      experimental data and actual clinical outcomes, which may be due to insufficient
      analyses and/or inappropriate animal models. We have explored suicide gene
      therapy by using various clinically relevant animal models and doubt the clinical
      use of maximal suicide gene expression, which has been generally recommended. To
      explore this subject further, we studied what expression level of suicide gene
      and what promoter led to the maximal clinical benefit in the case of hepatic
      metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral
      vectors that express herpes simplex virus thymidine kinase (HSV-tk) under
      different promoters were scrupulously investigated in 2 mouse models of hepatic
      metastasis of gastric cancer that possess clinical characteristics. Surprisingly,
      increases in HSV-tk expression beyond a certain point, achieved by the Rous
      sarcoma virus long terminal repeat promoter, not only enhanced the adverse side
      effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but
      also failed to further increase therapeutic potential. Moreover, the
      carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential
      of which had been underestimated, was much more useful-even in the case of low
      CEA-producing cancer-than had been previously reported. In conclusion, the
      optimal therapeutic expression level of a suicide gene is a novel concept and a
      crucial factor for successful cancer gene therapy. The present results, which
      contradict those of previous studies, alert researchers about possible problems
      with ongoing and future clinical trials that lack this concept.

PMID- 12500201
TI  - Clinical profile of autosomal dominant polycystic liver disease.
AB  - Most reports on the natural history, manifestations, and treatment of polycystic
      liver disease are based on the disease as it manifests in patients with autosomal
      dominant polycystic kidney disease (ADPKD). The purpose of this study was to
      develop a clinical profile of isolated autosomal dominant polycystic liver
      disease (ADPLD) using nonaffected family members as controls. The study included
      146 probands, known affected relatives, and first-degree relatives of affected
      individuals. Participants underwent a formalized medical history interview and
      physical examination, ultrasonographic examination of the liver and kidneys,
      magnetic resonance angiography of the brain, and echocardiography. Thirty-eight
      of the 49 individuals diagnosed with polycystic liver disease before
      participation in the study were or had been symptomatic. Of 97 previously
      undiagnosed at-risk individuals, 23 were affected, 39 were unaffected, and 35
      were indeterminate. Compared with patients with a negative or indeterminate
      diagnosis, those with polycystic liver disease had slightly higher levels of
      serum alkaline phosphatase and total bilirubin and lower levels of total
      cholesterol and triglycerides. Female patients had a significantly higher mean
      cyst score than male patients. The cysts were found to arise from the dilatation
      of biliary microhamartomas and from peribiliary glands. Structural mitral leaflet
      abnormalities were detected more frequently in affected than in indeterminate or
      nonaffected individuals. A vascular phenotype was detected in 5.6% of the
      patients with isolated ADPLD diagnosed clinically and/or by linkage analysis but
      in none of the unaffected patients. In conclusion, isolated ADPLD is
      underdiagnosed and genetically distinct from polycystic liver disease associated
      with ADPKD but with similar pathogenesis, manifestations, and management.

PMID- 12500202
TI  - Cyclooxygenase-derived products modulate the increased intrahepatic resistance of
      cirrhotic rat livers.
AB  - In cirrhotic livers, increased resistance to portal flow, in part due to an
      exaggerated response to vasoconstrictors, is the primary factor in the
      pathophysiology of portal hypertension. Our aim was to evaluate the response of
      the intrahepatic circulation of cirrhotic rat livers to the alpha(1)-adrenergic
      vasoconstrictor methoxamine and the mechanisms involved in its regulation. A
      portal perfusion pressure dose-response curve to methoxamine was performed in
      control and cirrhotic rat livers preincubated with vehicle, the nitric oxide
      synthase blocker N(G)-nitro-L-arginine (L-NNA), indomethacin cyclooxygenase (COX)
      inhibitor, L-NNA + indomethacin, or the thromboxane (TX) A(2) receptor blocker SQ
      29,548. TXA(2) production, COX-1 and COX-2 mRNA expression, and immunostaining
      for TXA(2) synthase were evaluated. Cirrhotic livers exhibited a hyperresponse to
      methoxamine associated with overexpression of COX-2 and TXA(2) synthase as well
      as with increased production of TXA(2). The hyperresponse to methoxamine of
      cirrhotic livers disappeared by COX inhibition with indomethacin but not after NO
      inhibition. SQ 29,548 also corrected the hyperresponse of cirrhotic livers to
      methoxamine. In conclusion, COX-derived prostanoids, mainly TXA(2), play a major
      role in regulating the response of cirrhotic livers to methoxamine.

PMID- 12500203
TI  - A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration
      in patients with hyponatremia: a multicenter, randomized, placebo-controlled
      trial.
AB  - Hyponatremia in advanced cirrhosis and ascites or congestive heart failure (CHF)
      is the result of an inappropriate increase in vasopressin secretion, which acts
      through activation of specific V(2) receptors in the distal renal nephron to
      increase water reabsorption. This study investigates the efficacy and safety of 3
      different doses of the V(2) receptor antagonist, VPA-985, in correcting
      hyponatremia over a 7-day inpatient study period. Forty-four hospitalized
      patients (33 patients with cirrhosis, 6 with CHF, and 5 with syndrome of
      inappropriate antidiuretic hormone (SIADH) were studied on a constant sodium
      intake, with VPA doses of 25, 125, and 250 mg twice daily or placebo. Serum
      sodium measurements were repeated after every daily dose, and the next dose
      withheld for excessive serum sodium rises. Fluid intake was adjusted according to
      previous 24-hour urinary outputs. Adverse events were based on clinical signs of
      dehydration or encephalopathy. VPA-985 produced a significant overall aquaretic
      response compared with placebo, with significant dose related increases in free
      water clearance (P <.05) and serum sodium (P <.05), without significant changes
      in orthostatic blood pressure or serum creatinine levels. Five patients (50%) on
      250 mg twice daily had to have medication withheld on multiple occasions. End-of
      study plasma vasopressin levels increased significantly in the 2 larger dose
      groups. In conclusion, VPA-985 appears effective and safe in appropriate doses in
      correcting abnormal renal water handling and hyponatremia in conditions
      associated with water retention. Higher doses of VPA-985 may produce significant
      dehydration and will require close monitoring with their use.

PMID- 12500204
TI  - Prospective evaluation of outcomes and predictors of mortality in patients with
      hepatopulmonary syndrome undergoing liver transplantation.
AB  - The hepatopulmonary syndrome (HPS) occurs in a subgroup of patients with
      cirrhosis and results from intrapulmonary vasodilatation, which may cause
      significant hypoxemia. Liver transplantation has emerged as a therapeutic option
      for patients with HPS based on retrospective case series and reports. However,
      morbidity and mortality appear to be increased after transplantation for HPS, and
      no prospective studies evaluating clinical features that may predict poor
      surgical outcome are available. Therefore, we prospectively evaluated the utility
      of the degree of hypoxemia, the arterial oxygen response to 100% oxygen
      administration, and the macroaggregated albumin (MAA) scan quantification of
      intrapulmonary shunting as predictors for outcome after liver transplantation.
      Our cohort consisted of 24 patients with cirrhosis and HPS who underwent liver
      transplantation over a 5-year period at 2 transplant centers who were followed at
      least 1 year after transplantation. All patients underwent preoperative
      evaluation for HPS with standardized methods. Seven patients (29%) died
      postoperatively, 5 of cardiorespiratory complications. All deaths occurred within
      10 weeks after transplantation. A preoperative arterial oxygen tension (PaO(2))
      of </= 50 mm Hg alone or in combination with a MAA shunt fraction >/= 20% were
      the strongest predictors of postoperative mortality. In conclusion, we found that
      mortality is increased after liver transplantation for HPS, particularly in
      patients with more severe hypoxemia and significant intrapulmonary shunting.
      Preoperative testing for the severity of HPS can be used to stratify patients
      according to the risk for postoperative mortality.

PMID- 12500205
TI  - Expression profiling in multistage hepatocarcinogenesis: identification of HSP70
      as a molecular marker of early hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from
      precancerous lesions and early HCC to a progressed form. Nodule-in-nodule-type
      HCC (progressed HCC within early HCC) represents the transition from early to
      progressed HCC and, therefore, is useful in molecular genetic analysis of HCC
      progression during multistage carcinogenesis. We compared expression profiles
      among 7 early components and 7 progressed components of nodule-in-nodule-type
      HCCs and their corresponding noncancerous liver tissues with oligonucleotide
      array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes
      provided a molecular signature that distinguished between early HCC components
      and their noncancerous liver tissues, and a set of 92 genes distinguished between
      progressed and early HCC components. Of these genes, the most abundantly up
      regulated gene in early HCC components (P <.001) was heat-shock protein 70
      (HSP70). Real-time quantitative reverse transcription polymerase chain reaction
      (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70
      revealed its significant overexpression in early HCC compared with precancerous
      lesions (P <.001) and in progressed HCC compared with early HCC (P <.001). In
      conclusion, molecular signatures were clearly different in noncancerous liver
      tissue as compared with the early and progressed components of nodule-in-nodule
      type HCC. Moreover, HSP70 could be a sensitive marker for the differential
      diagnosis of early HCC from precancerous lesion or noncancerous liver, a
      difficult distinction for pathologists due to very well differentiated histology
      with little atypia in early HCC.

PMID- 12500206
TI  - Increased lipopolysaccharide binding protein in cirrhotic patients with marked
      immune and hemodynamic derangement.
AB  - Intestinal bacterial overgrowth and translocation, both common in cirrhosis with
      ascites, may lead to the activation of monocytes and lymphocytes, increased
      levels of proinflammatory cytokines, and enhanced synthesis of nitric oxide
      present in cirrhosis. Bacterial endotoxin promotes the synthesis of
      lipopolysaccharide (LPS)-binding protein (LBP), and forms a LPS-LBP complex that
      binds to CD14. This study was designed to evaluate LBP levels and their
      correlation to the immune response and the hemodynamic status in cirrhotic
      patients. Plasma LBP, endotoxin, soluble CD14 (sCD14), cytokines, renin,
      nitrites, and systemic vascular resistance were determined before and 4 weeks
      after norfloxacin or placebo in 102 cirrhotic patients and 30 controls. LBP was
      elevated in 42% of ascitic cirrhotic patients (15.7 +/- 0.7 versus 6.06 +/- 0.5
      microg/mL, P <.01). In 60% of high LBP patients, endotoxin was within normal
      range. Among ascitic patients, those with high LBP showed greater (P <.05) levels
      of sCD14, tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), nitrites
      + nitrates (NOx)/creatinine, and renin, and lower vascular resistance. In the
      cirrhotic patients with high LBP, norfloxacin normalized (P <.01) LBP (from 16.6
      +/- 0.5 to 5.82 +/- 0.8 microg/mL) and sCD14; reduced the level of cytokines,
      NOx/creatinine, and renin; and increased vascular resistance; but lacked effect
      in patients with normal LBP. Portal pressure was unchanged after norfloxacin in
      another group of 18 cirrhotic patients with high and 19 with normal LBP. In
      conclusion, the subset of ascitic cirrhotic patients with marked immune and
      hemodynamic derangement is identified by increased LBP levels. Amelioration of
      these abnormalities by norfloxacin suggests the involvement of enteric bacteria
      or their products in the triggering of the process.

PMID- 12500209
TI  - Treatment of transfusion-dependent thalassemic patients infected with hepatitis C
      virus with interferon alpha-2b and ribavirin.

PMID- 12500210
TI  - Serum versus intrahepatic HCV RNA and liver histology in anti-HCV-positive serum
      PCR-negative individuals.

PMID- 12500211
TI  - The serology of the Addison-Gull syndrome.

PMID- 12500212
TI  - Fecal incontinence secondary to CAPD.
AB  - A 74-year-old patient who has developed fecal incontinence following continuous
      ambulatory peritoneal dialysis (CAPD) is presented. Incontinence was caused by
      elevated intra-abdominal pressure during peritoneal dialysis, which correlated
      with the volume of dialysate and position of the patient. The lowest pressure was
      found in the recumbent position. A change of dialysis schedule to continuous
      cycler peritoneal dialysis (CCPD) with "dry day" resulted in a disappearance of
      the symptoms.

PMID- 12500213
TI  - Prevalence of chronic kidney disease and decreased kidney function in the adult
      US population: Third National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Recently developed clinical practice guidelines and calibration of
      the Third National Health and Nutrition Examination Survey (NHANES III) serum
      creatinine assay provide a basis for estimating the prevalence and distribution
      of chronic kidney disease (CKD) in the United States using standardized criteria
      based on estimated glomerular filtration rate (GFR) and persistent albuminuria.
      METHODS: A nationally representative sample of 15,625 noninstitutionalized adults
      aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR),
      kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were
      estimated from calibrated serum creatinine level, spot urine albumin level, age,
      sex, and race. GFR was estimated using the simplified Modification of Diet in
      Renal Disease Study equation and compared with the Cockcroft-Gault equation for
      creatinine clearance (CCr). RESULTS: The prevalence of CKD in the US adult
      population was 11% (19.2 million). By stage, an estimated 5.9 million individuals
      (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%)
      had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6
      million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals
      (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals
      (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age
      is a key predictor of CKD, and 11% of individuals older than 65 years without
      hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates,
      CCr estimates showed a steeper decline with age and were lower in non-Hispanic
      blacks. CONCLUSION: CKD is common and warrants improved detection and
      classification using standardized criteria to improve outcomes. Am J Kidney Dis
      41:1-12.

PMID- 12500214
TI  - Hand-assisted laparoscopic radical nephrectomy-associated rhabdomyolysis with
      ARF.
AB  - Intraoperative rhabdomyolysis with resultant acute renal failure is a rare
      complication seen, most commonly, with urologic surgical procedures. Since the
      early 1990s, the refinement of laparoscopic techniques has permitted their
      application more broadly. Among the procedures to benefit from these less
      invasive surgical methods has been radical nephrectomy. In general, this has
      resulted in less postoperative pain and shorter convalescence. Nonetheless,
      laparoscopic radical nephrectomy still represents major surgery and is not free
      from operative risks. To highlight one of these risks, we present a case of a
      young, obese man with renal cell carcinoma who underwent a hand-assisted
      laparoscopic radical nephrectomy that was complicated by rhabdomyolsis resulting
      in acute renal failure (ARF). We discuss the clinical insults that contributed to
      the development of azotemia with particular attention paid to our current
      understanding of the pathogenesis of myoglobinuric ARF. In addition, we review
      the literature concerning surgery-associated, rhabdomyolytic ARF with the aim of
      providing clinicians guidance for the avoidance and early recognition of this
      rare, but very serious, surgical complication.

PMID- 12500215
TI  - Adult nondiarrhea hemolytic uremic syndrome associated with Shiga toxin
      Escherichia coli O157:H7 bacteremia and urinary tract infection.
AB  - About 15% of children with Shiga toxin (Stx) producing Escherichia coli (STEC)
      primarily of serotype O157:H7, gastrointestinal infection, and watery or bloody
      diarrhea, may develop hemolytic uremic syndrome (D+ HUS). Usually D+ HUS is not
      complicated by bacteremia and patients recover spontaneously without antibiotic
      treatment. We report here an adult case of a STEC O157:H7 urinary tract infection
      complicated by bacteremia and HUS that was not preceded by diarrhea (D- HUS).
      Cases of D- HUS need to be carefully examined for foci other than the
      gastrointestinal tract, and patients with E coli bacteremia should receive early
      antibiotic treatment as would any patient with sepsis.

PMID- 12500216
TI  - Bilateral pheochromocytomas and congenital anomalies associated with a de novo
      germline mutation in the von Hippel-Lindau gene.
AB  - A 12-year-old boy presented with severe hypertension, congenital microcephaly,
      severe hearing loss, developmental delay, cryptorchidism, and bilateral
      pheochromocytomas, without the phenotypic features of multiple endocrine
      neoplasia type II syndromes (MEN-2). Sequence analysis of the polymerase chain
      reaction (PCR)-amplified gnomic DNA identified a missense mutation at nucleotide
      451 of the von Hippel-Lindau (VHL) gene (A451G) that changes a codon for serine
      (AGT) to one for glycine (GGT) at amino acid position 80 (S80G). The sequence DNA
      analysis of the parents did not show a mutation in the VHL gene that was
      previously identified in their affected son. The observed constellation of
      microcephaly, deafness, cryptorchidism, developmental delay, hypertension, and
      bilateral pheochromocytoma in association with a VHL mutation A451G in a patient
      with negative family history has not previously been described in the literature.
      Knowledge that VHL mutation plays a critical role in sporadic pheochromocytoma
      should aid in the future diagnosis and treatment of this tumor. Genetic testing
      in known pheochromocytoma families is indicated to identify genetically abnormal
      subjects that carry the MEN-2, VHL, and glomus tumor gene mutations.

PMID- 12500217
TI  - Cigarette smoking and increased urine albumin excretion are interrelated
      predictors of nephropathy progression in type 2 diabetes.
AB  - BACKGROUND: Increased urine albumin excretion (UAE) predicts nephropathy
      progression in type 2 diabetes, whereas improved blood pressure (BP) control and
      angiotensin-converting enzyme (ACE) inhibition ameliorate both albuminuria and
      nephropathy progression. Cigarette smoking (CS) predicts nephropathy progression
      in patients with type 2 diabetes despite improved BP control and ACE inhibition.
      We tested the hypothesis that CS and increased UAE are interrelated predictors of
      nephropathy progression in patients with type 2 diabetes undergoing improved BP
      control and ACE inhibition. METHODS: We prospectively followed plasma creatinine
      (P(cr)) levels and UAE as albumin-creatinine (alb-cr) ratio for 63.9 +/- 0.6
      months in 84 patients with type 2 diabetes undergoing BP control with regimens
      including ACE inhibitors. RESULTS: Despite ACE inhibition and mean BP reduction
      from 113.7 +/- 1.8 to 92.3 +/- 0.6 mm Hg (P < 0.001), P(cr) increased (1.03 +/-
      0.02 to 1.25 +/- 0.04 mg/dL [91.1 +/- 1.8 to 110.5 +/- 3.5 micromol/L]; P <
      0.001) during follow-up. Regression analysis showed that entry alb-cr ratio, but
      not CS, predicted nephropathy progression when considering both factors together,
      but CS predicted progression only when excluding alb-cr ratio. Nephropathy
      progression was minimal for lower levels of alb-cr ratio at entry, but increased
      progressively for levels greater than 300. Alb-cr ratio increment during follow
      up directly correlated with nephropathy progression (r2 = 0.307; P < 0.001) and
      was greater in smokers than nonsmokers (1,878 +/- 346 versus 553 +/- 214; P <
      0.001). CONCLUSION: Data show that CS and increased UAE are interrelated
      predictors of nephropathy progression in patients with type 2 diabetes, and CS
      increases UAE in these patients despite improved BP control and ACE inhibition.

PMID- 12500218
TI  - TGF-beta 1 as a genetic susceptibility locus for advanced diabetic nephropathy in
      type 1 diabetes mellitus: an investigation of multiple known DNA sequence
      variants.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is a profibrotic
      cytokine suspected to be a crucial factor underlying glomerulosclerosis in
      advanced diabetic nephropathy. However, its potential role as a susceptibility
      gene for the development of this microvascular complication is unresolved.
      METHODS: We examined whether DNA sequence variants in the TGF-beta1 gene are
      associated with advanced diabetic nephropathy among Caucasians with type 1
      diabetes mellitus. These variants included three coding (Leu10Pro, Arg25Pro, and
      Thr263Ile) and two noncoding single-nucleotide polymorphisms (-800 and -509), as
      well as an insertion/deletion of a cytosine residue in intron 4. A large case
      control study design was used in which cases were patients with type 1 diabetes
      with advanced diabetic nephropathy (presence of persistent proteinuria or end
      stage renal disease [ESRD]; n = 298) and controls were patients who remained
      normoalbuminuric despite greater than 15 years of type 1 diabetes (n = 263).
      RESULTS: Genotype frequencies for all polymorphisms were in Hardy-Weinberg
      equilibrium. Genotype distributions of all six DNA sequence variants were very
      similar between cases and controls (P = not significant). There was no
      significant difference in genotype distributions among cases regardless of
      whether these individuals with diabetes were proteinuric at the time of
      examination or had already developed ESRD secondary to diabetic nephropathy.
      Stratified analyses according to diabetes duration and glycemic control likewise
      did not detect an association between DNA sequence variants and advanced diabetic
      nephropathy. CONCLUSION: Genetic variation at the TGF-beta1 locus is unlikely to
      confer significant susceptibility to advanced diabetic nephropathy in patients
      with type 1 diabetes mellitus.

PMID- 12500219
TI  - Clinicopathologic predictors of death and ESRD in patients with pauci-immune
      necrotizing glomerulonephritis.
AB  - BACKGROUND: Pauci-immune necrotizing glomerulonephritis (PING) occurs in various
      settings and has a very variable prognosis. We investigated whether
      clinicopathologic findings at the time of renal biopsy may predict major disease
      outcomes. METHODS: We evaluated 72 consecutive patients with biopsy-documented
      PING. Kaplan-Meier curves and Cox models assessed event rates and risk factors
      for death, end-stage renal disease (ESRD), and death or new ESRD (after the renal
      biopsy). RESULTS: During a follow-up of 305 person-years, 11 patients died, 13
      patients developed ESRD, and 16 patients died or developed new ESRD. Among
      patients first seen within 3 months of renal biopsy (incident cases), the 5-year
      mortality rate was 20%, whereas the death or new ESRD rate was 34%. In univariate
      analyses, older age, lower creatinine clearance, erythrocyte sedimentation rate,
      and percentages of abnormal glomeruli, glomeruli with fibrous crescents, and
      glomeruli with global sclerosis were significant predictors of mortality, whereas
      antineutrophil cytoplasmic autoantibodies with cytoplasmic staining conferred
      borderline protection. For ESRD, significant predictors included a greater
      creatinine level, lower hematocrit, interstitial fibrosis, tubular necrosis,
      greater C-reactive protein level, and percentages of abnormal glomeruli,
      glomeruli with extracapillary proliferation, cellular crescents, and global
      glomerulosclerosis. For death or new ESRD, predictors were fairly similar.
      Adjusting for baseline creatinine level, the risk for ESRD increased 1.78-fold
      (95% confidence interval [CI], 1.23 to 2.58) per each 10% increase in global
      sclerosis and 1.47-fold (95% CI, 1.05 to 2.07) per each 10% increase in glomeruli
      with cellular crescents. CONCLUSION: Global glomerulosclerosis and crescents in a
      renal biopsy are strong predictors of the long-term outcome of PING.

PMID- 12500220
TI  - Clinical and morphological prognostic factors in membranous nephropathy:
      significance of focal segmental glomerulosclerosis.
AB  - BACKGROUND: Progression of idiopathic membranous glomerulonephritis (IMGN) to
      renal insufficiency depends on various clinical and laboratory factors that have
      been taken into account in most therapeutic trials based on such aggressive drugs
      as alkylating agents or cyclosporine. However, few studies have envisaged the
      prognostic significance of morphological factors and their importance for
      stratification of patients enrolled in therapeutic trials. METHODS: Records of
      patients with membranous glomerulonephritis (MGN) from 1976 to 2001 from five
      nephrology units were reviewed retrospectively. Secondary causes were ruled out,
      especially occult malignancy. Eligible cases were analyzed according to clinical
      profile, abundance of proteinuria, blood pressure, and standard renal
      pathological characteristics, including MGN staging, vascular lesions, and degree
      of interstitial fibrosis on a semiquantitative scale. Renal survival curves from
      renal insufficiency were calculated by the Kaplan-Meier method. Mean follow-up
      was 68 months. RESULTS: Initial multiple regression analysis showed that the most
      significant prognostic variable was the presence of focal segmental
      glomerulosclerosis (FSGS)-type glomerular lesions (P < 0.001), and patients
      therefore were divided into two groups: 42 patients had MGN only (group I) and 30
      patients had superimposed FSGS (group II). Group II patients were more
      hypertensive, and all renal lesions were significantly more severe, with a higher
      mean stage of membranous lesions, more obsolescent glomeruli, greater mesangial
      proliferation, and worse interstitial fibrosis and vascular lesions. Renal
      survival for group II was significantly lower (P < 0.001, log-rank test). Only
      one remission occurred in group II, whereas 38% of group I patients experienced
      remission (P = 0.002). We pooled our results with those of three previous studies
      in the literature, totaling 282 patients (156 patients, MGN alone; 126 patients,
      MGN plus FSGS). Remission rates were 32% and 12.7%, respectively (P < 0.001). The
      prognostic value of hypertension was noted in three of the four series, including
      ours. CONCLUSION: FSGS lesions superimposed on IMGN are common and portend a
      significantly worse outcome in terms of nephrotic syndrome and renal
      insufficiency. Therefore, we consider that future therapeutic trials of IMGN
      should include case stratification based on the presence or absence of FSGS on
      pretreatment biopsy.

PMID- 12500222
TI  - Elevated serum levels of the type I and type II receptors for tumor necrosis
      factor-alpha as predictive factors for ARF in patients with septic shock.
AB  - BACKGROUND: Acute renal failure (ARF), a common and serious complication in
      patients with septic shock, has high mortality. Recent data suggest that
      proinflammatory cytokines may contribute to sepsis-associated ARF. METHODS: To
      examine the role of proinflammatory cytokines, we evaluated 537 patients enrolled
      in the placebo arm of the Norasept II study, of whom 112 patients (20%) developed
      ARF. RESULTS: By univariate analysis, the following factors were significantly
      associated with the development of ARF: male sex, younger age, increased heart
      rate, higher Acute Physiology and Chronic Health Evaluation II score, oliguria,
      increased blood urea nitrogen level, increased serum creatinine (Scr) level,
      decreased arterial pH, and increased serum potassium level. Although there were
      no statistically significant differences in serum levels of tumor necrosis factor
      alpha (TNF-alpha) or interleukin-6 between patients with and without ARF,
      elevated serum levels of the two soluble TNF-alpha receptors (S-TNF-RI and S-TNF
      RII) were strongly associated with the development of ARF (S-TNF-RI, 25 +/- 16
      versus 18 +/- 13 ng/mL; P = 0.00006; S-TNF-RII, 25 +/- 21 versus 18 +/- 17 ng/mL;
      P = 0.0007). Using forward stepwise regression analysis, elevated S-TNF-R level
      remained an independent predictor for ARF, even when we limited our analysis to
      patients with Scr levels of 1.4 mg/dL or less (< or =124 micromol/L) at study
      entry, suggesting that decreased renal clearance of S-TNF-R alone cannot account
      for this association. Elevated S-TNF-R level also was an independent predictor of
      mortality among patients developing ARF. CONCLUSION: S-TNF-R level is an
      independent predictor for the development of ARF and mortality. We speculate that
      elevated S-TNF-R levels may reflect a more intense inflammatory response.

PMID- 12500221
TI  - Predialysis Survey on Anemia Management: patient referral.
AB  - BACKGROUND: The Predialysis Survey on Anemia Management was designed to assess
      the care given to predialysis patients within 3 months of the start of
      hemodialysis or peritoneal dialysis (PD) therapy. In this presentation, we focus
      on demographic data and patient referral practices of patients who enter kidney
      centers. METHODS: We conducted a retrospective chart review of patients who had
      started hemodialysis or PD therapy between August 1999 and April 2000. All
      patients (age, 16 to 99 years) who entered 1 of the 779 centers in 21 European
      countries, Israel, or South Africa were included, except those for whom dialysis
      therapy was only started during an acute episode. Demographic characteristics,
      referral to kidney centers, comorbidities, drug treatments, major clinical
      events, and use of epoetin were documented. RESULTS: Mean creatinine clearance
      rate at the first visit to the kidney center was 18.2 mL/min (0.303 mL/s). Of all
      patients, greater than 35% had a creatinine clearance less than 10.0 mL/min
      (<0.167 mL/s) at their first visit. Overall, 87% of patients were initiated on
      hemodialysis therapy, and 13% were started on PD therapy. PD was used more often
      the longer a patient was under the care of a nephrologist. Of 4,333 new dialysis
      patients, 68% had a hemoglobin concentration of 11.0 g/dL or less (< or =110 g/L)
      at the first visit. CONCLUSION: The majority of patients in the survey had been
      under the care of a nephrologist for more than 12 months before the start of
      dialysis therapy. Nevertheless, most of these patients were anemic, and only a
      minority were on epoetin treatment.

PMID- 12500223
TI  - Predictors of ARF after cardiac surgical procedures.
AB  - BACKGROUND: In a pilot study, a low preoperative serum ferritin level predicted
      increased risk for acute renal failure (ARF) after cardiopulmonary bypass. It was
      hypothesized that this may reflect a decreased ability to bind free iron and
      defend against oxidative stress. However, the pilot study was performed in a
      small number of patients (n = 30) operated on by a single surgeon. The purpose of
      this study was to validate whether the serum ferritin level predicts ARF in a
      larger sample. METHODS: The present study evaluated 120 patients who underwent
      procedures performed by eight surgeons at another tertiary referral center. Data
      were collected prospectively and included patient characteristics, laboratory
      studies, procedure types, and postoperative course. ARF was defined as a 25% or
      greater increase in creatinine level 48 hours after surgery. RESULTS: The
      frequency of ARF was 42%, but no patient required dialysis therapy. Preoperative
      serum ferritin levels did not differ in the groups with and without ARF (158 +/-
      119 and 163 +/- 125 ng/mL, respectively), and rates of ARF did not differ when
      examined by ferritin quartiles. ARF was more frequent in those who underwent
      valve surgery (54% versus 35% in patients who did not undergo valve procedures; P
      = 0.044). The odds ratio for ARF after valve surgery was 2.58 (95% confidence
      interval, 1.06 to 6.29; P = 0.037), adjusted for longer times of surgery and
      aortic cross-clamp. Most excess ARF occurred in those who underwent aortic valve
      replacement (AVR; 62%; P = 0.014 versus nonvalve procedures). CONCLUSION: Low
      preoperative serum ferritin level was not confirmed to predict ARF after cardiac
      surgery. Valve procedures, particularly AVR, increased the risk for ARF.

PMID- 12500224
TI  - Chronic kidney disease as a risk factor for bleeding complications after coronary
      artery bypass surgery.
AB  - BACKGROUND: The aim of the study is to define the role of chronic kidney disease
      (CKD) as a risk factor for postoperative bleeding in patients undergoing coronary
      artery bypass graft (CABG) surgery. METHODS: This is a retrospective cohort study
      of 238 consecutive patients who underwent isolated CABG surgery. Patients were
      followed up for the event of a significant bleed, defined as administration of
      either three or greater units of packed red blood cells, three or greater units
      of platelets, three or greater units of fresh frozen plasma, or any
      cryoprecipitate within 72 hours after a CABG procedure or undergoing a surgical
      revision for bleeding. Glomerular filtration rate (GFR) at baseline was
      calculated using the Cockroft-Gault formula. A final multiple logistic regression
      model was selected from a large set of presurgical and intraoperative covariates
      by using backward elimination (P > 0.20). RESULTS: After controlling for age,
      sex, elective versus emergent surgery, intraoperative activated clotting time,
      serum albumin level, extracorporeal bypass time, and baseline hematocrit, we
      found that even mild levels of renal impairment were associated with increased
      risk for postoperative bleeding: patients with a GFR of 40 mL/min or less had six
      times the odds of postoperative bleeding than patients with a GFR greater than
      100 mL/min (odds ratio [OR], 6.51; 95% confidence interval [CI], 1.87 to 22.66);
      those with a GFR of 41 to 60 mL/min had nearly four times the risk (OR, 3.87; 95%
      CI, 1.21 to 12.35). Even patients with mild CKD at a GFR of 61 to 80 mL/min were
      at an elevated risk (OR, 2.11); however, the 95% CI of 0.79 to 5.64 included the
      null value. Similar results were found when using the cruder Kidney Disease
      Outcomes Quality Initiative classification of CKD. CONCLUSION: CKD is associated
      with risk for postoperative bleeding in patients undergoing CABG surgery, not
      only at more advanced stages, but probably at relatively mild levels of renal
      impairment, as well.

PMID- 12500225
TI  - The ENOS polymorphism is not associated with severity of renal disease in
      polycystic kidney disease 1.
AB  - BACKGROUND: The renal phenotype in autosomal dominant polycystic kidney disease
      (ADPKD) is highly variable. Although genetic and allelic heterogeneity explain
      part of this variability, significant intrafamilial differences in time to end
      stage renal disease (ESRD) indicate that genetic modifiers and the environment
      influence renal phenotype. Previously, a glutamic acid to aspartic acid
      polymorphism at residue 298 (E/D298) of the endothelial nitric oxide synthase
      (eNOS) gene ENOS was associated with disease severity in males with ADPKD.
      METHODS: We typed the E/D298 polymorphism in 215 mutation-defined polycystic
      kidney disease 1 (PKD1) patients from 80 families. In this population, 96
      patients had ESRD, with a median time to renal failure of 53 years. RESULTS:
      Distribution of ENOS genotypes was 86 (40%), 106 (49.3%), and 23 (10.7%) for EE,
      ED, and DD, respectively. The occurrence of hypertension was not significantly
      different between genotypes. Kaplan-Meier renal survival analysis showed no
      significant difference between genotypes, with a median age to ESRD of 53 years
      for all genotypes in the total population and 52, 52, and 51 years (men) and 57,
      53, and 55 years (women) for DD, DE, and EE, respectively. CONCLUSION: Although
      the D298 ENOS allele may be associated with lower vascular activity of eNOS, this
      did not correlate with severity of renal disease in this PKD1 population. An
      important difference between this study and one finding a modifying role for ENOS
      was the rigor in defining the PKD1 population. This study shows the importance of
      using mutation-characterized populations for association studies in ADPKD.

PMID- 12500226
TI  - Genetics, clinical and pathological features of glomerulonephritis associated
      with mutations of nonmuscle myosin IIA (Fechtner syndrome).
AB  - BACKGROUND: Fechtner syndrome (FTNS), also known as Alport-like syndrome, is a
      rare inherited condition characterized by progressive nephritis,
      macrothrombocytopenia, Dohle-like leukocyte inclusions, deafness, and cataract.
      Although it recently was shown that FTNS derives from mutation of MYH9, the gene
      for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA), its pathophysiological
      characteristics remain unknown. METHODS: We studied a large FTNS family in which
      10 components carried a missense mutation of MYH9 determining the D1424H
      substitution. RESULTS: All affected subjects presented with macrothrombocytopenia
      and leukocyte Dohle-like bodies consisting of macroaggregates of NMMHC-IIA, but
      only two subjects had major renal problems characterized by proteinuria and renal
      failure. Electron microscopy showed focal and segmental effacement of podocytes
      and loss of the interpodocyte slit diaphragm. Immunohistochemistry showed apical
      localization of NMMHC-IIA in tubular epithelia and less podocyte staining in the
      two patients, whereas it was diffuse in normal epithelia. Three patients
      presented with stable microhematuria, and another five patients had no renal
      lesions, although they carried the same mutation of MYH9. Therefore, MYH9
      mutation per se was responsible for platelet and leukocyte abnormalities, whereas
      additional predisposing conditions and/or environmental factors are necessary for
      nephropathy, cataract, and deafness. Looking at podocyte components conferring
      permselectivity properties to the kidney, we characterized the haplotype of
      podocin and found cosegregation of one specific allele in the two patients with
      nephrotic syndrome, suggesting a relationship between podocin features and
      proteinuria. CONCLUSION: Our study indicates a major role for the NMMHC-IIA
      abnormality in the pathogenesis of leukocyte, platelet, and kidney defects in
      FTNS. The basic feature in all cases is aggregation and compartmentation of NMMHC
      IIA. However, proteinuria and podocyte lesions are the hallmark of nephropathy in
      patients who develop renal failure, and podocin may have some function in this
      setting.

PMID- 12500227
TI  - The prevalence and treatment of depression among patients starting dialysis.
AB  - BACKGROUND: Depression is common in patients with end-stage renal disease (ESRD)
      and is associated with increased mortality, but little is known about depression
      in patients just after they start dialysis therapy. We sought to assess the
      prevalence of depressive symptoms in patients with ESRD starting dialysis
      therapy, identify patient characteristics associated with depression, and
      determine whether patients with serious depressive symptoms were receiving
      treatment. METHODS: We implemented a multicenter prospective cohort study at 14
      dialysis centers in Connecticut. Patients with ESRD who were 18 years and older
      were interviewed within 10 days of initiating dialysis therapy between November
      2000 and July 2001. The Beck Depression Inventory (BDI) was used to assess
      depressive symptoms. Chi-square tests were used to evaluate associations between
      several patient characteristics and depression, and multivariable logistic
      regression models were used to determine odds ratios (ORs) for depression, with
      adjustment for baseline variables. RESULTS: Among 123 patients, 44% (54 of 123
      patients) had scores above the validated cutoff value in the BDI for depression.
      In logistic regression analysis, depression was statistically significantly
      associated with Caucasian race (OR, 3.4; P = 0.02), lower self-rated quality of
      life (OR, 2.2; P = 0.003), and no previous acquaintances on dialysis therapy (OR,
      10.2; P = 0.03). Only 16% (9 of 54 patients) of depressed patients were being
      treated at enrollment; 13% (5 of 38 patients) of those with mild symptoms and 25%
      (4 of 16 patients) with more severe symptoms were being treated. CONCLUSION: Our
      results show that depressive symptoms are very common at the start of dialysis
      therapy, and specific characteristics are associated with a greater burden of
      depressive symptoms. Despite a high prevalence, treatment rates are low, even
      among patients with moderate to severe symptoms of depression.

PMID- 12500228
TI  - Effect of variability in anemia management on hemoglobin outcomes in ESRD.
AB  - BACKGROUND: Hemoglobin (Hgb) levels fluctuate in patients with end-stage renal
      disease over time. This study quantified Hgb level variability and the likelihood
      of falling within the Hgb level goal range of 11 to 12 g/dL. Implications on the
      percentage of patients exceeding 3-month rolling average Hgb levels of 12, 12.5,
      and 13 g/dL were determined. METHODS: Phase I (n = 65,009) tracked patients with
      Hgb values initially outside the goal range (<11 or >12 g/dL) during 2000.
      Correlation with facility-specific thresholds also was evaluated. Phase II (n =
      48,133) quantified variation in 3-month rolling average Hgb levels in a subset
      with greater than 10 months of data (mean Hgb, 11.4 +/- 1.3 g/dL). RESULTS: A
      total of 24,948 patients (38.4%) had Hgb levels between 11 and 12 g/dL. In only
      8% did Hgb levels consistently remain less than 11 g/dL, and in 18%, greater than
      12 g/dL all year. Twenty-nine percent (18,633 patients) moved from below to above
      target range or vice versa. Greater mean facility Hgb level correlated with a
      greater percentage of patients with Hgb levels greater than 10 g/dL (R2 = 0.49)
      and greater than 12.5 g/dL (R2 = 0.61). For facilities to have 90% or greater of
      patients with 3-month rolling average Hgb levels greater than 10 g/dL, 13% to 31%
      of patients will have 3-month rolling average Hgb values greater than 12.5 g/dL.
      The average individual patient is expected to have a +/-1.4-g/dL fluctuation in 3
      month rolling average Hgb levels per year. Despite increased mean Hgb levels and
      erythropoietin (EPO) and iron use, the spread of the Hgb distribution curve
      remained unchanged in the last 6 years. CONCLUSION: Variability caused by
      laboratory assays, biological factors, and therapeutic response determines
      patient Hgb level variability. Improving factors that can be manipulated (eg,
      standardizing EPO and iron algorithms) and adjustment of the target Hgb level
      range, specifically, by increasing the upper bound, likely will decrease the
      observed variability and further enhance the quality of anemia management.

PMID- 12500229
TI  - The provision and outcomes of diabetic care of hemodialysis patients.
AB  - BACKGROUND: Approximately 40% of hemodialysis patients have diabetes, yet little
      is known about their diabetic care. We sought to examine the provision and
      outcomes of diabetic care of hemodialysis patients. METHODS: We randomly selected
      188 hemodialysis patients with diabetes from nine facilities and identified the
      physicians providing their diabetic care. Patients and physicians reported on the
      care provided for six domains (diet, diabetes medications, hypertension,
      cholesterol, feet, and eyes). Chart abstraction was used to determine four
      outcomes (glucose control, blood pressure, albumin level, and cholesterol level).
      RESULTS: Most patients had a nephrologist, primary care physician, eye
      specialist, and podiatrist. Each domain of care generally was addressed on a
      regular basis. Nephrologists and primary care physicians differed on who should
      provide care for specific domains. For example, only 12% of nephrologists
      believed primary care physicians should manage hypertension, whereas 74% of
      primary care physicians believed they should manage hypertension (P < 0.001).
      Patient outcomes often were suboptimal, with one fourth to one half of patients
      having elevated glucose, blood pressure, or lipid levels. Many patients were not
      administered insulin, appropriate antihypertensives, or lipid-lowering
      medications. Primary care physicians felt frustrated by a lack of communication
      from nephrologists about laboratory results, medication changes, and procedures.
      CONCLUSION: Although hemodialysis patients with diabetes appear to receive timely
      care from a variety of physicians, patient outcomes often are poor. Medication
      use is suboptimal, nephrologists and primary care physicians disagree on their
      roles, and communication among physicians is limited. Interventions to improve
      outcomes of hemodialysis patients with diabetes should address these impediments.

PMID- 12500230
TI  - Native arteriovenous fistula blood flow and resistance during hemodialysis.
AB  - BACKGROUND: Measurement of vascular access flow (Qa) has been proposed as the
      ideal method for surveillance of native fistulae. However, debate exists about
      the influence of blood pressure (mean arterial pressure [MAP]) on Qa during
      dialysis. METHODS: During three consecutive dialysis treatments, 10 patients had
      paired measurements of Qa and MAP performed at 30, 60, 120, 180, 210, and 240
      minutes. Access resistance (AR; in peripheral resistance units, PRUs) was
      calculated from MAP and Qa values. RESULTS: Overall pooled coefficients of
      variation (CVs) for MAP, Qa, and AR were 8.4%, 12.3%, and 12.9%, respectively. A
      significant reduction in Qa and MAP occurred throughout the dialysis treatment
      (Qa, 104 mL/min; P = 0.008; MAP, 10.4 mm Hg; P = 0.007). Mean percentages of
      change in Qa for the first third compared with the middle and last thirds of the
      session were -4.6% +/- 11.15% (SD) and -9.6% +/- 10.5%, respectively. Thus, Qa
      varied between 11.4% and -30.6% from baseline during the last hour of dialysis
      treatments. A stronger correlation between MAP and Qa was seen in radiocephalic
      (r2 = 0.55; P < 0.0001) compared with brachiocephalic fistulae (r2 = 0.06; P =
      0.023). Mean AR was unchanged during the dialysis session (0.23 PRU; P = 0.358).
      AR for radiocephalic fistulae was significantly greater compared with
      brachiocephalic fistulae (6.03 +/- 3.90 versus 3.00 +/- 1.11 PRU; P < 0.0001).
      CONCLUSION: Qa could decrease up to 30% from baseline, potentially impairing the
      ability of Qa to predict impending vascular access failure. AR remained stable
      during the treatment and may be a more useful measure of vascular access
      performance as part of an access surveillance program.

PMID- 12500231
TI  - Prevalence and progression of peripheral arterial calcifications in patients with
      ESRD.
AB  - BACKGROUND: Peripheral arterial calcifications are seen frequently in patients
      with end-stage renal disease (ESRD). However, prevalence and progression, as well
      as contributing factors, never were investigated in an unselected incident cohort
      of dialysis patients. METHODS: We investigated 155 patients with ESRD at the
      beginning of dialysis therapy and followed them up prospectively during the first
      year of either hemodialysis (n = 106) or peritoneal dialysis treatment (n = 49).
      The prevalence and progression of arterial calcifications during the first year
      were graded by a single radiologist on standardized plain radiographs of the
      pelvis and calves. Findings were analyzed in relation to sex, age, diabetes
      mellitus, dialysis modality, total and high-density lipoprotein cholesterol
      levels, lipoprotein(a) (Lp[a]) level, apolipoprotein(a) kringle-IV repeat
      polymorphism, calcium level, phosphorus level, intact parathyroid hormone level,
      and homocysteine level. RESULTS: Patients with peripheral arterial calcifications
      at the start of renal replacement therapy (RRT) (n = 104) were significantly
      older (P < 0.001), had diabetes more often (P < 0.001), and had greater Lp(a)
      concentrations (P = 0.03) and a trend to greater total cholesterol
      concentrations. Patients with progression of calcifications during the first year
      of RRT had significantly greater homocysteine levels (P = 0.036). Logistic
      regression analysis showed that patients without calcifications either at the
      beginning or after 1 year of RRT were younger (P = 0.01) and had significantly
      lower homocysteine (P = 0.004) and Lp(a) levels (P = 0.03) and less frequently
      had diabetes mellitus (P = 0.04). CONCLUSION: Our observations suggest that the
      prevalence of peripheral arterial calcifications in patients with ESRD is related
      to age, diabetes mellitus, and Lp(a) and homocysteine levels. Progression of
      arterial calcifications might be related to high plasma homocysteine
      concentrations.

PMID- 12500232
TI  - Comorbidity and its change predict survival in incident dialysis patients.
AB  - BACKGROUND: Few studies have performed a comprehensive comparison of the
      prognostic importance of comorbidity to that of other case-mix factors
      influencing incident dialysis patients' survival. Longitudinal change in the
      comorbid illness burden of incident dialysis patients has not been measured.
      Comorbidity severity and its change may serve as important prognostic markers of
      survival, independent of other case-mix factors. METHODS: The Choices for Healthy
      Outcomes in Caring for End-Stage Renal Disease Cohort Study used the Index of
      Coexistent Disease (ICED) to assess comorbidity at the initiation of chronic
      dialysis treatment (1,039 incident patients) and during follow-up (733 patients).
      Using proportional hazards regression analyses, the relationship to survival of
      baseline ICED level and change in ICED level was examined. RESULTS: At the
      initiation of chronic dialysis treatment, 36% of patients were at ICED level 0 to
      1 (least comorbidity severity); 35%, level 2; and 29%, level 3. After
      multivariable adjustment, baseline ICED level was the strongest predictor of
      subsequent mortality. Compared with ICED level 0 to 1, relative risks for
      mortality were 1.9 (95% confidence interval, 1.3 to 2.6) for ICED level 2 and 2.8
      (95% confidence interval, 2.0 to 3.9) for ICED level 3. The prevalence and
      severity of most comorbid conditions increased during follow-up. After
      controlling for baseline ICED level and other factors, change in ICED level over
      time was significantly associated with mortality (P = 0.01). CONCLUSION: Indexing
      comorbidity when patients begin chronic dialysis therapy and recording the
      evolution of index scores yields a predictor of mortality risk that is
      independent of other case-mix factors.

PMID- 12500233
TI  - Factors associated with future amputation among patients undergoing hemodialysis:
      results from the Dialysis Morbidity and Mortality Study Waves 3 and 4.
AB  - BACKGROUND: Amputation is more common in hemodialysis patients than in the
      general population, but risk factors for amputation in this population have not
      been studied extensively. METHODS: We used the US Renal Data System Dialysis
      Morbidity and Mortality Study Waves 3 and 4 in combination with Medicare
      discharge data to identify factors associated with lower-extremity amputation
      (excluding toe amputations) in hemodialysis patients. We used stepwise
      multivariable logistic regression analysis to identify variables most strongly
      associated with amputation within 2 years of the study start date. RESULTS: Male
      sex, diabetes, previous diagnosis of peripheral vascular disease (PVD), mean
      systolic blood pressure, and elevated serum phosphorus level were associated with
      the outcome of amputation within 2 years of the study start date. Among patients
      without diabetes, a previous diagnosis of cardiac disease, longer time from
      initiation of dialysis therapy (vintage), and previous hospitalization for limb
      ischemia were associated with increased risk for future amputation. CONCLUSION:
      The importance of preventing amputation in this population cannot be
      overemphasized. The strength of the association of amputation with PVD makes a
      strong case for screening all dialysis patients for this disease. The association
      of amputation with serum phosphorus level reported here should be explored
      further because this may offer an avenue for future intervention to reduce
      amputation rates.

PMID- 12500234
TI  - Exercise counseling practices among nephrologists caring for patients on
      dialysis.
AB  - BACKGROUND: Patients on dialysis therapy are inactive, are at high risk for
      conditions that can be prevented or ameliorated by exercise, and often receive
      most of their care from their nephrologist. Exercise counseling by physicians can
      increase patients' levels of physical activity. The aim of the study is to
      determine the frequency of exercise assessment and counseling among practicing
      nephrologists, characteristics of nephrologists who provide exercise counseling
      to their dialysis patients, and barriers to exercise counseling perceived by
      nephrologists. METHODS: A 25-item survey regarding exercise counseling was
      administered to nephrologists attending the World Congress of Nephrology meeting
      in 2001. RESULTS: Five hundred five nephrologists completed the survey. Overall,
      38% reported "almost always" or "often" assessing patient level of physical
      activity and counseling inactive patients to increase activity. Older (P <
      0.0001), more active (P = 0.033), and women (P = 0.018) nephrologists, as well as
      those who provided primary care to more of their patients (P = 0.007), were more
      likely to provide exercise counseling. Nephrologists who do not provide routine
      counseling were more likely to endorse lack of time (P < 0.0001), lack of
      confidence in their ability to counsel patients (P < 0.0001), and lack of
      conviction that patients will respond as barriers to counseling (P = 0.01). In
      addition, noncounseling nephrologists were more likely to believe that other
      medical issues were more important than exercise (P = 0.01). CONCLUSION: Rates of
      exercise counseling among nephrologists are low, although dialysis patients are a
      high-risk group unlikely to receive advice about exercise from other health care
      providers. The low rates of counseling, particularly among younger nephrologists,
      could be addressed by including information about counseling in fellowship
      training and/or practice guidelines for the care of patients on dialysis therapy.

PMID- 12500235
TI  - Recombinant EPO therapy increases erythrocyte expression of complement regulatory
      proteins.
AB  - BACKGROUND: One of the complications of hemodialysis (HD) therapy is anemia
      caused by erythropoietin (EPO) deficiency. Recombinant EPO (rEPO) has been used
      routinely as a supplemental treatment. Erythrocyte expression of the complement
      regulatory proteins decay accelerating factor (DAF) and CD59 restricts complement
      activation and inhibits hemolysis. We hypothesized that the efficacy of rEPO
      treatment may be caused in part by the ability of rEPO to increase erythrocyte
      expression of DAF and CD59. METHODS: DAF, CD59, and complement receptor 1 (CR1)
      levels were analyzed for a group of 95 HD patients and compared with those of a
      control group. To evaluate effects of discontinuation of rEPO therapy, rEPO
      therapy was stopped for 12 HD patients until hematocrits decreased to less than
      25%. DAF and CD59 levels then were reanalyzed. RESULTS: In the 95 HD patients,
      three factors correlated significantly: DAF and CD59 (r = 0.642), DAF and CR1 (r
      = 0.503), and CD59 and CR1 (r = 0.324), whereas no correlations were found in the
      group of 42 healthy controls. In the experiment in which rEPO therapy was
      discontinued, 8 of 12 patients reached the defined level of anemia 4 to 7 weeks
      after rEPO treatment had been withheld. Both DAF and CD59 levels decreased
      significantly after discontinuation of rEPO therapy (P < 0.01). DAF and CD59
      levels increased in all 8 patients after rEPO treatment was reinitiated (P <
      0.01), and CR1 levels increased in 5 of 8 patients. Four of 12 patients showed no
      evidence of anemia after discontinuation of rEPO treatment. In these patients,
      DAF, CD59, and CR1 levels did not change before or after withholding rEPO
      therapy. CONCLUSION: One of the mechanisms mediating the efficacy of EPO therapy
      is increased DAF and CD59 expression.

PMID- 12500236
TI  - Impact of socioeconomic status on the quality of life of ESRD patients.
AB  - BACKGROUND: Socioeconomic status (SES) has been associated with the incidence of
      end-stage renal disease (ESRD); however, the impact of SES on the quality of life
      (QOL) of these patients has not been clearly defined. METHODS: One hundred
      eighteen patients were prospectively evaluated at the beginning of dialysis
      treatment and reassessed (n = 90) after an average of 7 months. QOL was measured
      by means of the Medical Outcomes Survey 36-Item Short Form (SF-36).
      Classification of SES was according to validated criteria of the Brazilian
      Association of Research Institutes. RESULTS: Mean scores for SF-36 dimensions
      were decreased in patients with low compared with high SES, with greater
      differences noted during follow-up. At this time, mean scores for SF-36 scales
      for the low- and high-SES groups were as follows: Functional Capacity, 43 +/- 31
      versus 68 +/- 26 (P < 0.01); Physical Aspect, 34 +/- 36 versus 56 +/- 38; Pain,
      55 +/- 31 versus 80 +/- 28 (P < 0.01); General Health Status, 60 +/- 21 versus 67
      +/- 19; Vitality, 42 +/- 25 versus 59 +/- 16 (P < 0.05); Social Aspect, 53 +/- 32
      versus 81 +/- 21 (P < 0.01); Emotional Aspect, 49 +/- 44 versus 70 +/- 41; and
      Mental Health, 51 +/- 27 versus 70 +/- 22 (P < 0.05), respectively. These
      differences were more pronounced than expected for an age- and sex-matched sample
      of the Brazilian general population. Multivariate analysis showed that SES
      continued to significantly affect all QOL dimensions, explaining 5.5% to 14.1% of
      variation in scales. CONCLUSION: SES is an important factor associated with QOL
      in patients with ESRD. Further studies to determine optimum interventions and
      measures in groups with lower SES may be important to improve QOL outcomes and
      reduce their morbidity.

PMID- 12500237
TI  - Cell-associated magnesium and QT dispersion in hemodialysis patients.
AB  - BACKGROUND: Impaired magnesium (Mg) homeostasis has been implicated in a variety
      of cardiovascular disturbances, including ventricular arrhythmias and changes in
      the interval between the onset of wave Q to the end of wave T (QT interval) on
      electrocardiogram. Cardiac arrhythmias are common in patients on hemodialysis
      therapy. METHODS: We investigated the relationship between QT interval corrected
      for heart rate (QTc) dispersion and Mg content in peripheral blood mononuclear
      cells (PBMC) of chronic hemodialysis patients treated with high-dose calcium
      carbonate providing Mg in excess (group I; n = 18) or low-dose calcium carbonate
      and smaller Mg load (group II; n = 13). RESULTS: Mean Mg content in PBMC of group
      I patients (27.9 +/- 4.2 [SD] micromol/L/mg protein) was significantly greater
      than in group II patients (10.4 +/- 4.1 micromol/L/mg protein; P < 0.05) and
      greater in both groups than in healthy control subjects (2.75 +/- 0.6
      micromol/L/mg protein; P < 0.05). Mean QTc dispersion was significantly longer
      (74.6 +/- 21.4 milliseconds) in group I than group II (37.8 +/- 13.1
      milliseconds; P < 0.02) and longer in both groups than in controls (27.3 +/- 9.6
      milliseconds; P < 0.05). After dialysis, in both groups of patients, cell
      associated Mg (c-a Mg) levels and QTc dispersion were significantly greater (P <
      0.05) than before dialysis started. One week after stopping calcium carbonate
      treatment, group 1 patients showed significant reductions in predialytic c-a Mg
      levels (to 19.5 +/- 9.8 micromol/L/mg protein; P < 0.05) and QTc dispersions (to
      48.9 +/- 23.7 milliseconds; P < 0.05). Plasma Mg and other electrolyte
      concentrations prior to and during hemodialysis did not correlate with QTc
      dispersion. CONCLUSION: Prolongation of QTc dispersion in patients on chronic
      hemodialysis therapy could be, at least in part, a consequence of increased
      concentrations of c-a Mg resulting from excess daily Mg intake.

PMID- 12500238
TI  - An association between coronary artery calcification score, lipid profile, and
      selected markers of chronic inflammation in ESRD patients treated with peritoneal
      dialysis.
AB  - BACKGROUND: Chronic uremia is considered a proinflammatory state associated with
      high cardiovascular morbidity and mortality. The aim of the present study is to
      evaluate the potential relationship between the prevalence of coronary artery
      calcification (CAC) and selected factors that may be involved in the process of
      atherogenesis (lipid profile, acute-phase reactants, growth factors, and
      cytokines). METHODS: The study group consisted of 43 patients (19 women, 24 men)
      with a mean age of 50.6 +/- 13.4 years treated with peritoneal dialysis (PD) for
      a median period of 15 months (range, 2 to 96 months). Only patients with sinus
      rhythm were included. CAC score (CaSc) was measured using multirow spiral
      computed tomography (MSCT). As parameters of lipid profile, total cholesterol,
      low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)
      cholesterol, and triglycerides were assayed. C-reactive protein (CRP) and
      fibrinogen represented the level of acute-phase activation. Proinflammatory
      cytokines (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-alpha]),
      leptin, and basic fibroblast growth factor (bFGF) also were measured. RESULTS:
      Median CaSc equaled 17.9 Agatston units (range, 0 to 5,502 Agatston units). No
      calcification was detected in 20 subjects (46.5%; CaSc < 10 Agatston units). CaSc
      correlated with age (R = 0.57; P < 0.0001), body mass index (R = 0.42; P <
      0.005), and serum leptin (R = 0.3; P < 0.05) and CRP levels (R = 0.38; P < 0.05).
      The correlation with PD therapy duration was borderline statistically significant
      (P = 0.063). Patients with the greatest values for CaSc (> 400 Agatston units)
      were characterized by significantly greater levels of IL-6, bFGF, and CRP
      compared with subjects with a CaSc less than 10 Agatston units (P < 0.05 for
      all). Patients with history of coronary artery disease (CAD) had significantly
      greater CaSc values (median, 778.6 versus 3.3 Agatston units; P < 0.001) compared
      with those without CAD. Serum triglyceride levels were significantly greater and
      HDL cholesterol levels were significantly lower in patients with CAD. The first
      group also was characterized by significantly greater serum TNF-alpha (P < 0.01)
      and CRP levels (P < 0.005). In multiple regression analysis, only age was
      independently associated with CaSc (beta = 0.45; P = 0.002). CONCLUSION: Our
      results may suggest an association between CAC and chronic inflammation activity
      in the mentioned group of patients. To our knowledge, this is the first study
      reporting the prevalence of CAC in PD patients using the MSCT method. The
      association between CaSc results and classic, as well as inflammatory, risk
      factors for CAD found in this study should be interpreted with caution because of
      its method limitations (cross-sectional design, heterogeneity of study
      population, and small number of studied patients).

PMID- 12500239
TI  - Quantitative tissue polymerase chain reaction for Epstein-Barr virus in pediatric
      solid organ recipients.
AB  - BACKGROUND: Infections caused by herpes virus, in particular, Epstein-Barr virus
      (EBV), remain a major challenge in solid organ transplantation. Little is known
      about the significance of tissue EBV load. METHODS: Twenty-three tissue biopsy
      specimens (19 kidney, 3 gastrointestinal, and 1 tonsil specimen) and 2
      bronchoalveolar lavage specimens from 14 pediatric transplant recipients (10
      kidney, 3 liver, 1 combined transplant) were subject to tissue EBV polymerase
      chain reaction (PCR) semiquantitative analysis and enzyme-linked immunosorbent
      assay (ELISA) methods. Results of biopsies were correlated with clinical data.
      RESULTS: Five of 14 patients had clinically diagnosed EBV disease: 2 patients
      presented with a septic picture with multiorgan failure and pneumonitis; 1
      patient had mononucleosis; 1 patient had an increase in serum creatinine level,
      lymphadenopathy, and chronic fatigue; and 1 patient had EBV nephritis. These 5
      patients underwent 12 biopsies at the time of clinically active infection; 8
      biopsies had positive results (up to 111 copies/10 microL of extracted DNA).
      Conversely, 1 of the remaining 13 tissue biopsy specimens from asymptomatic
      patients had positive results on ELISA, but undetectable viral load, whereas 8
      patients had a positive EBV immunoglobulin G titer with historic evidence of EBV
      replication in the blood. No patient without evidence of EBV had positive EBV
      tissue PCR results. CONCLUSION: Increased EBV load was found in more than 50% of
      patients, pointing to a previously underrecognized importance of EBV detection in
      tissues from transplant recipients. The presence of EBV in tissue correlated with
      the presence of viremia, whereas tissue PCR had 100% specificity. EBV load should
      be included in biopsy evaluation.

PMID- 12500240
TI  - Ichthyotoxic ARF after fish gallbladder ingestion: a large case series from
      Vietnam.
AB  - Fish gallbladders are consumed in rural areas of Asia as a traditional medicine
      to improve symptoms of arthritis, decreased visual acuity, and impotence.
      Consumption of large amounts of this traditional medicine can result in systemic
      toxicities; in particular, acute renal failure. We reviewed records of all
      admissions to Cho Ray Hospital (Ho Chi Minh City, Vietnam) between January 1995
      and December 2000 after this ingestion. Clinical courses and outcomes were
      similar in 16 of 17 patients. Within hours, patients experienced profuse vomiting
      (n = 16) and diarrhea (n = 15). All developed acute renal failure, with a mean
      serum creatinine concentration of 14.7 +/- 3.9 mg/dL (1,299.5 +/- 344.8
      micromol/L). Four patients administered intravenous fluid (IVF) developed
      extracellular fluid volume overload, as did 1 patient not administered IVF. Time
      to peak creatinine concentration was 8.6 +/- 3.0 days, which was accompanied by
      decreased urine volume (174.7 +/- 161.6 mL/24 h). Blood pressure remained normal,
      with a mean arterial pressure of 91 +/- 12 mm Hg. Twelve patients required renal
      replacement therapy. A mean of 1.9 +/- 1.1 hemodialysis sessions was performed
      per patient. Sixteen patients recovered renal function; 1 patient died of
      fulminant hepatic failure. Kidney biopsies showed features of acute tubular
      injury. Acute renal failure after fish gallbladder ingestion is characterized by
      a failure to respond to IVF, an 8.6-day interval to peak creatinine level,
      frequent need for dialysis therapy, and findings on renal biopsy consistent with
      acute tubular necrosis. Acute renal failure after fish gallbladder ingestion has
      an excellent prognosis. However, death from fulminant hepatic failure can occur.

PMID- 12500241
TI  - Improvement in lower-extremity peripheral arterial disease by nocturnal
      hemodialysis.
AB  - A 42-year-old man with end-stage renal disease (ESRD) was referred for conversion
      to nocturnal hemodialysis (NHD) therapy from conventional hemodialysis (CHD)
      therapy because of refractory intermittent claudication secondary to peripheral
      arterial disease (PAD). The patient was initiated on CHD therapy in 1976 and
      subsequently had undergone two unsuccessful renal transplantations. While on CHD
      therapy, his clinical course was complicated by worsening vascular and soft
      tissue calcification. Extensive dystrophic soft-tissue calcification was noted
      bilaterally in his hands, lower extremities, and sacral region, requiring
      surgical excision. Lower-extremity arterial Doppler scans documented vascular
      calcification and a pronounced decrease in peripheral arterial flow bilaterally.
      After conversion to NHD therapy (7.5 h/session five times weekly), the patient
      became symptom free and had significant clinical improvements in (1)
      hemodynamics, measured by clinic blood pressure and two-dimensional
      echocardiography, (2) biochemical profile, and (3) a sustained improvement in
      arterial Doppler flow measured by duplex Doppler ultrasound. We conclude that NHD
      was able to improve lower-extremity PAD in our patient. Further observational and
      interventional studies are required to investigate the therapeutic potential of
      NHD for the treatment of PAD in patients with ESRD.

PMID- 12500243
TI  - ATP6B1 gene mutations associated with distal renal tubular acidosis and deafness
      in a child.
AB  - A large proportion of autosomal recessive distal renal tubular acidosis (RTA) is
      associated with mutations in the ATP6B1 gene encoding the B1 subunit of H+
      ATPase. H+-ATPase is one of the key membrane transporters for net acid excretion
      in the alpha-intercalated cells of the medullary collecting duct. Sensorineural
      hearing loss frequently accompanies this type of distal RTA. Mutational analysis
      of the ATP6B1 gene in a 9-year-old Korean boy with distal RTA and sensorineural
      hearing loss found 2 heterozygous missense point mutations. Although a single
      case report, this is the second report documenting ATP6B1 mutations in recessive
      distal RTA with sensorineural hearing loss after the original report by Karet et
      al and confirms the novelty of these mutations.

PMID- 12500242
TI  - Conjugated bile acid replacement therapy reduces urinary oxalate excretion in
      short bowel syndrome.
AB  - BACKGROUND: Patients with short bowel syndrome (SBS) have steatorrhea, in part
      because of bile acid malabsorption that causes decreased bile acid secretion into
      the duodenum and consequent fat maldigestion. In SBS patients with colon in
      continuity, luminal calcium forms calcium fatty acid soaps rather than
      precipitating as insoluble calcium oxalate. Soluble oxalate is hyperabsorbed by
      the colon leading to hyperoxaluria and an increased risk for renal calcium
      oxalate stones and deposits. The authors hypothesized that oral ingestion of
      conjugated bile acids would increase fat absorption and thereby decrease calcium
      fatty acid soap formation and oxalate hyperabsorption. METHODS: The effect of
      conjugated bile acid replacement therapy (9 g/d) on fecal fat excretion and urine
      oxalate excretion was measured in an appropriate patient, utilizing the metabolic
      balance technique. The effects of chronic bile acid replacement therapy on
      oxalate excretion and nutritional status also were measured in a 3-month
      outpatient study. RESULTS: Natural conjugated bile acid replacement therapy
      reduced fecal fat excretion from 119 to 79 g/d (Delta40 g/d), and urinary oxalate
      excretion from 87 to 64 mg/d (966 to 710 micromol/d; Delta23 mg/d).
      Cholylsarcosine, a synthetic conjugated bile acid, had similar but less powerful
      effects. During a 3-month outpatient trial of natural conjugated bile acids (9
      g/d), urine oxalate decreased to normal levels (27 mg/d) in association with
      weight gain, decreased hunger, and decreased hyperphagia. CONCLUSION: Conjugated
      bile acid replacement therapy reduced fecal fat excretion, reduced urinary
      oxalate excretion, and improved nutritional status in a patient with SBS with
      colon in continuity, hyperoxaluria, and oxalate nephrolithiasis.

PMID- 12500244
TI  - Resolution of typical lipoprotein glomerulopathy by intensive lipid-lowering
      therapy.
AB  - Lipoprotein glomerulopathy (LPG), characterized by glomerular lipoprotein
      thrombi, presumably composed of abnormal apolipoprotein E (apoE), leads to a
      progressive decline in renal function and eventually results in end-stage renal
      failure. A successful treatment for LPG has not yet been established. The authors
      treated a 36-year-old woman with LPG and exhibiting a nephrotic syndrome using an
      intensive lipid-lowering therapy consisting of fenofibrate (300 mg), niceritrol
      (750 mg), ethyl-icosapentate (1,800 mg), and probucol (500 mg). After the start
      of treatment, a remarkable decrease in urinary protein excretion and improvement
      in the hyperlipidemia were obtained; proteinuria was no longer detected 11 months
      after the initiation of treatment. A second biopsy performed 11 months after the
      initiation of treatment showed the complete disappearance of the lipoprotein
      thrombi that had been observed in a diffuse and global manner in the first renal
      biopsy. These findings suggest that typical LPG could be regressed if the
      abnormal lipoproteinemia is controlled sufficiently.

PMID- 12500245
TI  - A whitened face woman with nephrotic syndrome.
AB  - Skin whitening cream from developing countries is a recognized source of chronic
      mercury poisoning. The authors report on a 34-year-old Indonesian domestic helper
      who presented with nephrotic syndrome secondary to membranous nephropathy. It was
      subsequently found that she used a skin whitening cream regularly that was found
      to contain a mercury level of almost 2,000 times above the allowable limit. Her
      blood and urinary mercury levels were both grossly elevated. Her symptoms
      improved after she stopped using the cream. However, she returned to her home
      country before chelating therapy could be arranged. Because mercury-containing
      skin products are still widely available in developing countries, the use of
      these products should be considered a possible cause of membranous nephropathy in
      immigrants from those countries.

PMID- 12500246
TI  - Can evidence drive the development of a sound national EPO reimbursement policy?

PMID- 12500247
TI  - A 14-year-old male with asymptomatic proteinuria and hearing loss.

PMID- 12500249
TI  - Will fasciotomy help in the patients with crush syndrome?

PMID- 12500250
TI  - Intravenous versus subcutaneous EPO: anything to do with pure red cell aplasia
      complication.

PMID- 12500252
TI  - A man with backache and renal failure.
AB  - Backache, a common symptom, is rarely caused by infection of the lumbar discs.
      The authors present the case of a 60-year-old man with a Staphylococcus aureus
      septicemia and associated lumbar discitis in whom a pauci immune crescentic
      glomerulonephritis and renal failure developed. Treatment with antibiotics and
      not immunosuppressive agents resulted in improved renal function with a discharge
      creatinine level of 1.87 mg/dL (165 micromol/L). This case highlights an
      association of pauci-immune crescentic glomerulonephritis with discitis that
      responded to antibiotic therapy alone.

PMID- 12500253
TI  - Quiz page. Stones in the kidney allograft and bladder. Nephrolithiasis is common
      after transplantation. Cyclosporine often leads to chronic hyperuricemia and the
      formation of uric acid stones.

PMID- 12500255
TI  - Ultrastructure of endothelial cells under flow alteration.
AB  - Endothelial cells are stable and quiet in normal animals. They arrange regularly
      and have a smooth lumen surface and thin endothelial wall. According to Thoma's
      principle (1893) and Kamiya and Togawa's principle (1980) on the relationship of
      the vascular diameter to flow alteration, blood flow is in equilibrium to the
      diameter and in a physiological state. That is to say, there is no fast flow or
      slow flow. To understand the nature of the endothelial cells, we should
      investigate endothelial cells under flow alteration to break the equilibrium
      state. Endothelial cells under increased flow were studied in arteries with an
      arteriovenous fistula or in the capillaries of myocardium with volume-overloaded
      hearts or of the skeletal muscle by electrical stimulation. Those under decreased
      flow were studied by the closure of the fistula or by ceasing the stimulation.
      Endothelial cells in the coarctation of the arteries were also observed.
      Endothelial cells were activated by increased flow in the arteries and
      capillaries, while they were inactivated by decreased flow. Endothelial
      activation is characterized as lumen protrusions, increase of cytoplasmic
      organelles, abluminal protrusions, basement membrane degradation, internal
      elastic lamina degradation in the arteries, and sproutings in the capillaries.
      These are ultrastructurally comparable to angiogenesis. Endothelial inactivation
      is characterized by the decrease of endothelial cell number with apoptosis, which
      is ultrastructurally comparable to angioregression. We assume that endothelial
      cells respond to increased flow by angiogenesis and to decreased flow by
      angioregression.

PMID- 12500256
TI  - Endothelial cell-matrix interactions.
AB  - Dynamic interactions between endothelial cells and components of their
      surrounding extracellular matrix are necessary for the invasion, migration, and
      survival of endothelial cells during angiogenesis. These interactions are
      mediated by matrix receptors that initiate intracellular signaling cascades in
      response to binding to specific extracellular matrix molecules. The interactions
      between endothelial cells and their environment are also modulated by enzymes
      that degrade different matrix components and thus enable endothelial invasion.
      Recent reports on gene targeting in mice have confirmed the role of two classes
      of matrix receptors, integrins and cell surface heparan sulfate proteoglycans,
      and a group of matrix degrading proteolytic enzymes, matrix metalloproteinases,
      in angiogenesis. The significance of endothelial cell-matrix interactions is
      further supported by several ongoing clinical trials that analyze the effects of
      drugs blocking this interaction on angiogenesis-dependent growth of human tumors.

PMID- 12500257
TI  - Vascular wall: potential target for the physicochemical effects of cis
      unsaturated free fatty acids.
AB  - Diets rich in monounsaturated cis-FFA (cis FFA) are associated with a significant
      reduction of cardiovascular risk. Although several different mechanisms have been
      proposed to explain this protective effect, the biochemical processes involved
      have not been fully elucidated. It has been shown that upon their incorporation
      into the plasma membrane, cis FFA induce a marked perturbation of the lipid
      domains, altering membrane fluidity as well as lipid-lipid and lipid-protein
      interactions in the bilayer plane. During the last few years, several lines of
      evidence have shown that these perturbations disrupt the activity of several
      membrane proteins and enzymatic systems. As a result, several critical
      transmembrane signaling systems, including the Ins(1,4,5)P(3)/DAG/[Ca(2+)](i),
      the cAMP/PKA, and the voltage-operated Ca(2+) influx are strongly inhibited by
      cis FFA in different experimental models. Furthermore, this inhibition is
      associated with alterations in the timing of the cell cycle as well as in the
      final steps of the secretory pathway. We propose that this complex set of
      biological actions exerted by cis FFA at the plasma membrane may contribute to
      explain the protective roles that these molecules appear to exert on the vascular
      wall.

PMID- 12500258
TI  - Genetic abnormalities of the endothelium.
AB  - Endothelial cell dysfunction plays an important role in the development and
      progression of cardiovascular and other disease. The purpose of this review is to
      discuss some of the genetic diseases known to adversely affect endothelial
      function. Although the list is exhaustive, we focus our discussion on primary
      pulmonary hypertension, diabetes mellitus, Alzheimer's disease, Crohn's disease,
      Von-Hippel-Lindau disease, familial Mediterranean fever, thrombotic
      microangiopathy, and key vascular malformations. Endothelial dysfunction results
      from a complex interplay between genetic and environmental factors. This review
      highlights some of the growing body of evidence implicating endothelial
      dysfunction as an important mediator of diverse diseases.

PMID- 12500259
TI  - Placenta: regularization of neovascularization. Microvascularization pattern of
      the rabbit term placenta.
AB  - Mammalian blastocyst produces membranes that gradually attach in the endometrial
      epithelium and establish a close relationship between fetal and maternal
      circulatory systems for physiologic exchange. This fact results in the formation
      of a combined organ, the placenta. Placentation includes extensive
      neovascularization in maternal and embryonic placental tissues. Recent studies,
      particularly of genetically altered mice, have greatly improved our understanding
      of the molecular basis of the development of the vascular system. Numerous
      factors have been implicated in the regulation of the neovascularization process
      of the placenta. The aim of this article is to highlight briefly the pattern
      circulation of the rabbit term placenta as an example of the microvascularization
      of hemochorial placenta typical of humans and to summarize the main factors
      responsible for modulating the growth of decidual placental vessels and the
      vasculogenesis of the basal plate.

PMID- 12500260
TI  - Perturbations in paracrine control of the circulation: role of the endothelial
      derived vasomediators, endothelin-1 and nitric oxide.
AB  - Central to the control of vascular resistance in the systemic and pulmonary
      circulation and at the solid organ level is the function of the endothelial
      derived vasomediators, endothelin-1 (ET-1) and nitric oxide. Regulation of steady
      state levels of ET-1 and endothelial nitric oxide synthase (eNOS) mRNAs
      represents an early and influential step in their biosynthesis and is highly
      responsive to exogenous stimuli. ET-1 is expressed from a rapidly inducible
      promoter to generate a highly labile mRNA. Conversely, the eNOS promoter
      generates a constitutive level of a very stable mRNA and utilizes
      posttranscriptional mechanisms to modulate mRNA expression. The response of these
      genes in models of cellular activation commonly reflects a reciprocal pattern of
      regulation, namely, transcriptional induction of ET-1 and destabilization of the
      eNOS mRNA. Elucidating the mechanisms influencing ET-1 and eNOS mRNA is providing
      novel insight into endothelial gene regulation and providing opportunities for
      future therapeutic strategies.

PMID- 12500261
TI  - Hormone regulation of endothelial apoptosis and proliferation in vessel
      regression and angiogenesis.
AB  - Apoptosis and endothelial proliferation represent two adverse events which take
      place during vessel regression and angiogenesis, respectively. Apoptosis, an
      intrinsically activated programmed cell death, regulates cell elimination during
      vessel regression. In contrast, angiogenesis involves endothelial cell
      proliferation, migration, and vascular formation. Several molecules, including
      growth factors and cytokines, produced by endothelial cells and by other cells
      within the vicinity of the capillary network, regulate apoptosis and
      angiogenesis. Hormones and endocrine peptides acting via specific receptors
      located on the endothelial and perivascular stromal cells also have been found to
      be involved in the regulation of these two major antagonistic processes. The need
      for a better understanding of the mechanisms involved in hormone regulation of
      endothelial cell during apoptosis and angiogenesis is of great importance. The
      accumulating knowledge of hormone regulation may contribute to the introduction
      of new therapeutic strategies targeting the endothelial cells.

PMID- 12500262
TI  - Mast cells and angiogenesis.
AB  - There is much evidence that angiogenesis is related to mast cells. Mast cells
      accumulate in many angiogenesis-dependent situations, including tumor growth,
      rheumatoid arthritis, ovulation, would healing, and tissue repair. Several mast
      cell mediators are angiogenic and regulate endothelial cell proliferation and
      function. Stem cell factor, vascular endothelial growth factor, epidermal growth
      factor, basic fibroblast growth factor, and platelet-derived growth factor induce
      chemotactic migration of mast cells to sites of neovascularization. Mast cell
      products such as tryptase also degrade connective tissue matrix to provide space
      for neovascular sprouts. Angiogenesis has been proposed as a target for
      anticancer therapy and for treatment of inflammatory disorders such as rheumatoid
      arthritis. Future studies on the cascade of angiogenic events, including mast
      cell-target cell interaction, and various intracellular signaling pathways are
      indicated to provide a new approach for the treatment of cancer and inflammatory
      disorders and for tissue repair.

PMID- 12500263
TI  - Role of growth factors and their receptors in proliferation of microvascular
      endothelial cells.
AB  - Investigations over the last decade have established the essential role of growth
      factors and their receptors during angiogenesis. The biological significance of
      VEGF, EGF, and bFGF is mediated by their receptors, which belong to the family of
      tyrosine kinase receptors: Flt-1 (VEGFR-1), KDR (VEGFR-2), EGFR, FGFR-1, FGFR-2,
      FGFR-3, and FGFR-4. Deeper understanding of the mechanism of activation of these
      growth factor receptors has allowed the development of a new pharmacological
      strategy aimed at controlling cancer cell proliferation. The results of a large
      body of preclinical as well as early clinical studies conducted suggest that
      targeting the growth factor receptors could represent a significant contribution
      to cancer therapy.

PMID- 12500264
TI  - Effects of steroid hormones on vascular functions.
AB  - The purpose of this review is to present reported findings of effects of steroids
      on vascular function and to discuss the biological significance in vascular
      physiology and pathology. Steroid hormones play various roles in vascular
      functions through the specific receptor localized in the endothelium and
      underlying vascular smooth muscle cells (VSMCs). Estrogen replacement therapy in
      postmenopausal women is in general associated with a reduction in mortality from
      cardiovascular disease and the beneficial effects of estrogens are caused by
      modulation of lipid metabolism, expression of leukocyte adhesion molecules, and
      migration of VSMCs in the vascular wall. Estrogens also play a role as
      vasodilators through an increment in nitric oxide (NO) production in endothelium
      or modulation of calcium homeostasis in VSMCs. Some progestin molecules partially
      oppose the effects of estrogens on vascular functions, but striking differences
      exist among the types of molecules. Testosterone shows a vasorelaxant response,
      but detailed actions of androgens on vascular functions remain unknown.
      Glucocorticoids act on vasoconstriction through reduced prostacyclin production,
      increased alpha-adrenoceptor numbers, and inhibition of NO synthase, while
      mineralocorticoids induce hypertrophy and hyperplasia of VSMCs and perivascular
      fibrosis and cause peripheral vascular resistance, in addition to changes in
      vascular electrocyte permeability. Some rapid actions of steroids are mediated by
      "nongenomic" responses in vascular tissues. Recent studies have also demonstrated
      that steroid-producing or -metabolizing enzymes are expressed in the vascular
      wall, suggesting the local regulation of steroids in the vascular system. Thus,
      steroid hormones greatly influence vascular functions and an understanding of the
      mechanisms may provide new means to prevent vascular diseases.

PMID- 12500265
TI  - Inhibition of angiogenesis at endothelial cell level.
AB  - Targeting of proliferating endothelial cells may allow a new therapeutic strategy
      against malignant tumors. Endothelial cells are easily accessible through the
      blood stream and genetically stable, reducing the possibility of acquiring drug
      resistance. There are numerous candidates for angiogenesis targets of drug
      development, e.g. a single endothelial cell has 2,000-20,000 different receptors
      on a cell membrane and inside a cell there are hundreds of second messengers.
      Inhibitors that are active at endothelial cells can be placed in three main
      groups inducing blockage of endothelial cell activator, direct inhibition of
      endothelial cells, inhibition of endothelial specific signaling. This review
      summarizes different approaches already in clinical trials. Specific effort is
      taken to give a view of and a new perspective over clinically relevant basic
      mechanisms, e.g. VEGF, ETS and radionanotargeting. It is clear that aggressive
      development work both at the preclinical and clinical levels is still needed;
      however, breakthroughs in applied therapies are expected at any time.

PMID- 12500266
TI  - Physiological and pathological angiogenesis in the endocrine system.
AB  - Formation of new blood vessels occurs in many physiological states (during
      development of the embryo, cycling changes of the female reproductive tract), as
      well as in pathological processes (such as diabetic retinopathy and wound
      healing). Angiogenesis has been shown to be related to tumor formation,
      prognosis, and response to treatment in many tumor types. Intratumoral
      microvessels can be related to tumor behavior or hormone secretion in different
      endocrine tumors. For example, invasive prolactinomas are more vascular than
      noninvasive adenomas; a surgical approach is more successful in
      macroprolactinomas with lower microvessel density. A higher number of
      microvessels have been found in papillary thyroid carcinomas during recurrences.
      A correlation between microvessel count and prognosis in papillary and medullary
      thyroid carcinomas has been suggested. Several stimulating and inhibiting factors
      involved in the regulation of angiogenesis have been identified. Among them,
      vascular endothelial growth factor (VEGF) has been shown to be critically
      involved in angiogenesis and also in the neovascularization of solid tumors.
      Dopamine agonists (already in clinical use for prolactinomas) have potent
      inhibitory actions on VEGF signaling, and thus may be a new tool in
      antiangiogenic therapy. Secretion of VEGF in the great majority of human
      pituitary adenomas is inhibited by dexamethasone. This suggests that
      glucocorticoids can be considered in the treatment of certain pituitary tumors.
      The cyclic nature of angiogenesis in the female reproductive tract indicates that
      stimulation or inhibition of paracrine angiogenic factors may lead to new
      approaches for being able to influence reproductive endocrine disorders.
      Experimental and clinical aspects of interactions between angiogenic factors and
      tumor growth of the endocrine system are also discussed.

PMID- 12500267
TI  - Angiogenesis in wound repair: angiogenic growth factors and the extracellular
      matrix.
AB  - Angiogenesis is critical to wound repair. Newly formed blood vessels participate
      in provisional granulation tissue formation and provide nutrition and oxygen to
      growing tissues. In addition, inflammatory cells require the interaction with and
      transmigration through the endothelial basement membrane to enter the site of
      injury. Angiogenesis, in response to tissue injury, is a dynamic process that is
      highly regulated by signals from both serum and the surrounding extracellular
      matrix (ECM) environment. Vascular endothelial growth factor, angiopoietin,
      fibroblast growth factor, and transforming growth factor beta are among those
      most potent angiogenic cytokines in wound angiogenesis. The cooperative
      regulation of them is essential for wound repair. Migration of endothelial cells
      and development of new capillary vessels during wound repair is dependent on not
      only the cells and cytokines present but also the production and organization of
      ECM components both in granulation tissue and in endothelial basement membrane.
      The ECM regulates angiogenesis by providing scaffold support and signaling roles.
      They also serve as a reservoir and modulator for growth factors. Laminins are the
      major noncollagenous ECM of endothelial basement membrane. Two newly recognized
      laminins, 8 and 10, are the major laminins produced by human dermal microvascular
      endothelial cells. Laminin 10 is highly expressed in blood vessels around skin
      wounds. Laminin 8 promotes dermal endothelial cell attachment, migration, and
      tubule formation. Integrins with either beta 1 or alpha v subunits are the major
      cellular surface receptors for ECM molecules and mediate the interactions between
      cells and ECM during wound angiogenesis.

PMID- 12500268
TI  - Microfilaments and microtubules maintain endothelial integrity.
AB  - The endothelium is a highly metabolic monolayer of cells regulating numerous
      physiological and pathological functions that maintain the permeability and
      thromboresistant functions of the endothelium. The structure and function of the
      endothelial cytoskeleton prevents vascular disease by regulating the structure of
      the endothelium to act as a resting molecular barrier to atherogenic proteins and
      by becoming an activated layer of migrating cells to repair denuding injuries.
      The purpose of this review is to examine the structure of the endothelial
      cytoskeleton and its roles in cell-cell and cell-substratum adhesion, cell
      signaling, and regulation of wound repair. Studies focused on the cellular and
      molecular biology of the structure and function of the endothelial cytoskeleton
      and in wound repair are reviewed. The cytoskeleton is a key regulator in
      maintaining endothelial integrity and in restoring integrity following injurious
      denudation, such as those that occur in the pathogenesis of atherosclerosis.
      Actin microfilaments and their associated adherens junctions and focal adhesions
      are important regulators of cell signaling, cell locomotion, cell adhesion, and
      wound repair mechanisms. Various proteins have been implicated in controlling
      cytoskeletal-based endothelial function and repair such as tyrosine
      kinases/phosphatases and the Rho family of proteins. The normal function of the
      endothelium is highly dependent on the endothelial cytoskeleton. Disruption and
      dysfunction of the cytoskeleton may result in impairment of endothelial function,
      subsequently tipping the balance towards vascular disease. Thus, an understanding
      of the cellular and molecular biology of the endothelial cytoskeleton is
      essential in our understanding of the pathogenesis of vascular disease,
      especially atherosclerosis.

PMID- 12500269
TI  - Three-pool model of white matter.
AB  - PURPOSE: To investigate the use of a three-pool relaxation model to measure
      myelin, myelinated-axon, and mixed water-pool fractions in white matter (WM)
      during myelination. MATERIALS AND METHODS: MRI at 1.9 Tesla, and conventional
      spin-echo imaging were used to acquire T1 and T2 relaxation data in 15 normal
      children ranging in age from 3 months to 13 years 4 months. Three equations with
      three unknowns were solved to calculate three water-pool fractions for each child
      in a frontal association-fiber area and a frontal-parietal projection-fiber area.
      The temporal trend of the fractions was compared with a theoretical three-pool
      myelination model. RESULTS: The myelin level in the projection-fiber area rose
      earlier than in the association-fiber area following the standard caudal-to
      rostral trend. The temporal trend of the three-pool fractions followed that
      predicted by the theoretical myelination model in both brain areas. The
      myelinated-axon and mixed pool sizes were significantly different in the two WM
      areas following early myelination, although their myelin pools were similar. T1
      values correlated more highly with the myelinated-axon and mixed pool fractions
      than with the myelin pool fraction. CONCLUSION: The three-pool relaxation model
      provides measurements of water-pool fractions in WM that follow values predicted
      during myelination.

PMID- 12500270
TI  - Is myo-inositol a measure of glial swelling after stroke? A magnetic resonance
      study.
AB  - PURPOSE: To determine whether the hypothesis that the phenomenon of persistent
      cytotoxic edema in the subacute stage of ischemic stroke is in fact associated
      with the glial population. This is done by assessing the evolution of both the
      apparent diffusion coefficient (ADC) and the glial-specific marker myo-inositol
      (Ins) in a group of patients, and by comparing the results with the total
      cellular density by means of the creatine (Cre) level. MATERIAL AND METHODS:
      Twenty-two patients with stroke in the territory of the middle cerebral artery
      were each examined once only at a time ranging from eight hours to six days
      following the onset of symptoms. Lesion-to-contralateral values of ADC were
      obtained based on diffusion-weighted echo-planar imaging. Short TE single-voxel
      proton magnetic resonance ((1)H MR) spectroscopy was used for quantification of
      cerebral metabolites in infarcted regions. Their levels were also compared with
      those in homotopic contralateral regions. RESULTS: In the stroke lesion, there
      was a significant correlation between ADC and the Ins level, albeit less
      pronounced than that for Cre. During different pathophysiological stages between
      12 hours and three days, the Ins-to-Cre ratio increased by a factor of two and
      returned to apparently normal thereafter. CONCLUSION: Our study provides the
      first demonstration of a relationship between persistent cytotoxic edema and the
      glial population in the context of cell swelling due to osmotic imbalance in
      stroke patients.

PMID- 12500271
TI  - Wavelet statistics of functional MRI data and the general linear model.
AB  - PURPOSE: To improve the signal-to-noise ratio (SNR) of functional magnetic
      resonance imaging (fMRI) data, an approach is developed that combines wavelet
      based methods with the general linear model. MATERIALS AND METHODS: Ruttimann et
      al. (1) developed a wavelet-based statistical procedure to test wavelet-space
      partitions for significant wavelet coefficients. Their method is applicable for
      the detection of differences between images acquired under two experimental
      conditions using long blocks of stimulation. However, many neuropsychological
      questions require more complicated event-related paradigms and more experimental
      conditions. Therefore, in order to apply wavelet-based methods to a wide range of
      experiments, we present a new approach that is based on the general linear model
      and wavelet thresholding. RESULTS: In contrast to a monoresolution filter, the
      application of the wavelet method increased the SNR and showed a set of clearly
      dissociable activations. Furthermore, no relevant decrease of the local maxima
      was observed. CONCLUSION: Wavelet-based methods can increase the SNR without
      diminishing the signal amplitude, while preserving the spatial resolution of the
      image. The anatomical localization is strongly improved.

PMID- 12500272
TI  - Diffusion tensor MRI of myocardial fibers and sheets: correspondence with visible
      cut-face texture.
AB  - PURPOSE: To test the hypothesis that the primary, secondary, and tertiary
      eigenvectors of the diffusion tensor (DT) measured with DT-MRI correspond to the
      fiber, sheet, and sheet normal directions, respectively, we compared DT-MRI data
      with the texture visible in the cut face of fresh bovine myocardium. MATERIALS
      AND METHODS: DT-MRI and optical images obtained under identical conditions were
      compared objectively. Ink prints were made of the cut tissue, and the local
      orientations within these images were defined by analysis of local
      autocorrelations for regions matching DT-MRI pixels. Deviation angles between the
      cleavage orientations and the diffusion eigenvectors were analyzed in eight
      specimens sliced in three orthogonal planes. RESULTS: Root-mean-square (RMS)
      angular disparity was 11 degrees between the first eigenvectors of the DT and the
      fiber direction, 14 degrees between the second eigenvector and the sheet
      direction, 14 degrees between the third eigenvector and the sheet normal
      direction, and 15 degrees between the tensor orientation in the imaging plane and
      the cleavage orientation of the cut face. CONCLUSION: The results support a
      parallel relationship between the eigenvectors of the DT and symmetry axes of the
      myocardial architecture. Specifically, the first, second and third eigenvectors
      correspond to the fiber, sheet, and sheet normal directions, respectively.

PMID- 12500273
TI  - Assessment of aorto-iliac disease with magnetic resonance angiography using
      arterial phase 3-D gradient-echo and interstitial phase 2-D fat-suppressed
      spoiled gradient-echo sequences.
AB  - PURPOSE: To evaluate magnetic resonance angiography (MRA) of the pelvis for the
      examination of the aorto-iliac system using arterial phase 3-D gradient echo and
      interstitial phase 2-D fat-suppressed spoiled gradient-echo (SGE), with
      comparison to surgery and angiography. MATERIALS AND METHODS: Ninety MR
      angiograms performed on 79 consecutive patients were analyzed, retrospectively,
      for the presence of narrowing, aneurysm, and dissection. Comparisons were made
      with angiography and surgery in 50 examinations, and a weighted kappa statistic
      test was applied to assess agreement. MR examinations were performed at 1.5T 3-D
      fast imaging in steady state precession (FISP) acquired immediately, and fat
      suppressed SGE in the interstitial phase following gadolinium administration.
      RESULTS: MRA had overall sensitivities of 100% at aortic segments, 100% at common
      iliac, 93.8% at external, and 95.7% at internal iliac, and specificities of 100%
      at aortic segments, 89.7% at common iliac, 95.2% at external iliac, and 88.7% at
      internal iliac in detection of vascular disease. The agreement of MRA with the
      angiography and surgery yielded a weighted kappa statistic of 0.97 at the aortic,
      0.94 at the common, 0.85 at the external, and 0.82 at the internal iliac
      segments. CONCLUSION: This study demonstrates an excellent performance of MRA in
      the evaluation of aorto-iliac arterial system and almost perfect agreement with
      angiography and surgery at all vascular levels.

PMID- 12500274
TI  - Stenosis detection in forearm hemodialysis arteriovenous fistulae by multiphase
      contrast-enhanced magnetic resonance angiography: preliminary experience.
AB  - PURPOSE: To assess the feasibility and accuracy of multiphase contrast-enhanced
      magnetic resonance angiography (CE-MRA) in patients with dysfunctioning
      hemodialysis arteriovenous fistulae (AVF), using digital subtraction angiography
      (DSA) as the standard of reference. MATERIALS AND METHODS: Fifteen patients with
      dysfunctioning AVF (eight radiocephalic and seven graft AVF) underwent CE-MRA.
      Dysfunction was defined as a flow decline of more than 25% in 1 month measured by
      dilutional flow measurements. CE-MRA was performed during injection of 35 mL of
      gadolinium-DTPA. The CE-MRA sequence consisted of a time-resolved series of 10
      scans, each lasting approximately 10 seconds. The technical parameters were
      TR/TE/FA/voxel = 5.4/1.6/40/3.1 mm(3), and a rectangular surface reception coil
      was used. All patients were scheduled to undergo DSA at which an intervention was
      carried out when a stenosis >or=50% was seen. Two observers, unaware of each
      other's findings and the findings at DSA, quantified the number and degree of
      stenosis in the failing AVF. Image quality for CE-MRA and DSA was scored on a 3
      point scale. The diagnostic performance of CE-MRA was analyzed with receiver
      operator characteristic (ROC) analysis. RESULTS: CE-MRA and DSA examinations were
      performed without side effects in all 15 patients. Image quality was scored
      significantly better on CE-MRA (observer 1: CE-MRA, 2.0; DSA, 1.3; P =.001;
      observer 2: CE-MRA, 2.0; DSA, 1.4; P =.002). Interobserver agreement for
      detection of >or=50% stenosis was 0.81 (95% confidence interval (CI) = 0.71-0.92)
      for CE-MRA and 0.69 (95% CI = 0.55-0.84) for DSA. ROC analysis revealed a mean
      area under the curve of 0.78. On the patient level, at the >or=50% threshold,
      mean sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were 100% (95% CI = 69%-100%), 10% (95% CI = 0%-78%), 70%
      (95% CI = 38%-92%), and 100% (95% CI = 50%-100%), respectively. At the >or=75%
      threshold, mean sensitivity, specificity, PPV, and NPV were 75% (95% CI = 20%
      99%), 78% (95% CI = 39%-98%), 55% (95% CI = 12%-96%), and 89% (95% CI = 52%
      100%), respectively. CONCLUSION: CE-MRA is a useful diagnostic tool for detecting
      stenoses in flow-declined hemodialysis AVF prior to interventional DSA.

PMID- 12500275
TI  - Clinical blood flow quantification with segmented k-space magnetic resonance
      phase velocity mapping.
AB  - PURPOSE: To evaluate the accuracy of segmented k-space magnetic resonance phase
      velocity mapping (PVM) in quantifying aortic blood flow from through-plane
      velocity measurements. MATERIALS AND METHODS: Two segmented PVM schemes were
      evaluated, one with seven lines per segment (seg-7) and one with nine lines per
      segment (seg-9), in twenty patients with cardiovascular disease. A non-segmented
      (non-seg) PVM acquisition was also performed to provide the reference data.
      RESULTS: There was agreement between the aortic flow curves acquired with
      segmented and non-segmented PVM. The calculated systolic and total flow volume
      per cycle from the seg-7 and the seg-9 scans correlated and agreed with the flow
      volumes from the non-seg scans (differences < 5%). Sign tests showed that there
      were no statistically significant differences (P-values > 0.05) between the
      segmented and the non-segmented PVM measurements [corrected]. Seg-9, which was
      the fastest among the three sequences, provided adequate spatial and temporal
      resolution (> 10 phases per cycle). CONCLUSION: Segmented k-space PVM shows great
      clinical potential in blood flow quantification.

PMID- 12500276
TI  - Initial in vivo experience with steady-state subzone-based MR elastography of the
      human breast.
AB  - PURPOSE: To describe initial in vivo experiences with a subzone-based, steady
      state MR elastography (MRE) method. This sparse collection of in vivo results is
      intended to shed light on some of the strengths and weaknesses of existing
      clinical MRE approaches and to indicate important areas of future research.
      MATERIALS AND METHODS: Elastic property reconstruction results are compared with
      data compiled from the limited existing body of published studies in breast
      elasticity. Mechanical parameter distributions are also investigated in terms of
      their implications for the nature of biological soft tissue. Additionally, a
      derivation of the statistical variance of the elastic parameter reconstruction is
      given and the resulting confidence intervals (CIs) for different parameter
      solutions are examined. RESULTS: By comparison with existing estimates of the
      elastic properties of breast tissue, the subzone-based, steady-state MRE method
      is seen to produce reasonable estimates for the mechanical properties of in vivo
      tissue. CONCLUSION: MRE shows potential as an effective way to determine the
      elastic properties of breast tissue, and may be of significant clinical interest.

PMID- 12500277
TI  - Suspected early or mild chronic pancreatitis: enhancement patterns on gadolinium
      chelate dynamic MRI. Magnetic resonance imaging.
AB  - PURPOSE: To assess whether measuring the pattern of pancreatic enhancement on
      gadolinium chelate dynamic magnetic resonance imaging (MRI) is helpful for
      diagnosis of suspected early or mild chronic pancreatitis. MATERIALS AND METHODS:
      In this retrospective study, 24 patients with suspected early or mild chronic
      pancreatitis, classified by imaging criteria of equivocal chronic pancreatitis
      (ultrasound, computed tomography [CT] or ERCP) grading, had dynamic MRI that
      included unenhanced, arterial dominant, early venous, and late venous phases of
      contrast enhancement. Twenty patients without pancreatic diseases also had the
      dynamic sequence as a control group. The signal intensity was measured at the
      pancreatic head, body, and tail on all phases, and for each, the signal intensity
      ratio (SIR, the signal intensity in postcontrast divided by that in precontrast)
      was calculated. Two radiologists independently reviewed the images of the
      patients with suspected early or mild chronic pancreatitis for pancreatic
      morphologic abnormalities without knowing the results of signal intensity
      measurements. RESULTS: On unenhanced images, there was no significant difference
      of signal intensity between control and pancreatitis groups (P < 0.05). In the
      pancreatitis group, but not in the control group, the unenhanced signal intensity
      of the pancreatic head and body were significantly higher than that of the tail
      (P < 0.05). In the control group, the greatest enhancement (highest SIR) after
      injection was in the arterial phase (1.89 +/- 0.31), significantly higher than
      that in the early venous phase (1.68 +/- 0.17, P < 0.01) and in the late venous
      phase (1.61 +/- 0.15, P < 0.001). The pancreatitis group, however, had an
      arterial phase SIR (1.65 +/- 0.23) that was significantly lower than its early
      venous phase SIR (1.75 +/- 0.22, P < 0.05) and lower than the arterial phase SIR
      of the control group (P < 0.01). The presence of an SIR less than 1.73 in the
      arterial phase and/or a delayed peak enhancement after contrast agent
      administration had a sensitivity and specificity of diagnosing early or mild
      chronic pancreatitis of 92% and 75%, respectively. This sensitivity was
      significantly higher than the sensitivity of 50% for diagnosis based on
      morphologic abnormalities (P < 0.05). CONCLUSION: Measuring pancreatic signal
      intensity on gadolinium chelate dynamic MRI is helpful for diagnosing early or
      mild chronic pancreatitis, especially before apparent pancreatic morphologic or
      signal intensity changes are present.

PMID- 12500278
TI  - Automated quantitative evaluation of diseased and nondiseased renal transplants
      with MR renography.
AB  - PURPOSE: To present a method of automated parametric quantification of dynamic MR
      enhancement curves of renal transplants and evaluate the disease-discriminating
      properties of the resulting MR renography (MRR) data. MATERIALS AND METHODS: This
      study included 27 patients with nondiseased renal transplants and eight patients
      with diseased renal transplants. The examination was repeated in 10 patients and
      the reproducibility of the enhancement parameters was estimated by analysis of
      variance (ANOVA). The disease-discriminating properties of the transplant volumes
      and enhancement parameters were tested with t-tests and logistic regression
      analysis. RESULTS: The enhancement parameters were reproducible. The mean
      medullary nephronal washout rate (lambda1) and cortical arterial blood volume
      (mu0) were lower in diseased renal transplants. The combination of these
      parameters was a strong predictor of renal transplant disease (area under ROC
      curve 0.98; 95% confidence interval 0.96-1.0). CONCLUSION: Automated parametric
      quantification of cortical and medullary enhancement is feasible and allows the
      accurate detection of nonsurgical disease in renal transplants by MRR.

PMID- 12500279
TI  - Renal diffusion and BOLD MRI in experimental diabetic nephropathy. Blood oxygen
      level-dependent.
AB  - PURPOSE: To investigate the possibility of using combined blood oxygen level
      dependent (BOLD) imaging and diffusion-weighted imaging (DWI) to detect
      pathological and physiological changes in renal tissue damage of the kidney
      induced by chronic renal hyperfiltration. MATERIALS AND METHODS: The apparent
      diffusion coefficient (ADC) and the T(2)* value within the inner compartments of
      the kidneys of 17 rats with diabetes mellitus were compared with the results
      obtained from a control group (N = 16). The influence of dynamic changes of the
      renal function on the blood-oxygen saturation was evaluated by comparing the
      T(2)* values before and after the active reduction of tubular transport by
      furosemide injection. RESULTS: All compartments of the diabetic kidney showed
      significantly (P < 0.05) lower T(2)*-values compared to the control group. In
      particular, the very low values in the outer stripe (OS) of the outer medulla
      (OM) (T(2)*-normal: 69.4 +/- 10.9 msec; T(2)*-diabetic: 51.4 +/- 13.9 msec)
      indicated either hypoxia due to hyperfiltration, or renal blood volume changes.
      Diffusion imaging of the same area showed significantly lower ADC values (ADC
      normal: 1.45 +/- 0.26; ADC-edema: 1.19 +/- 0.25 [10(-9)m(2)/s]) that correlated
      with pathological findings on histopathology. The injection of furosemide
      significantly (P < 0.05) increased T(2)* in all compartments of both populations
      while the ADC remained unchanged. CONCLUSION: BOLD-contrast imaging appears to be
      able to depict tissue at risk from ischemia by revealing information about the
      balance between tubular workload and delivery of oxygen, and thus may reflect a
      measure of the reserve capacity. The diffusion measurements apparently reveal
      complementary information. Although ADC imaging is not sensitive to the current
      energy metabolism, it appears toreflect the pathological changes within the
      issue. Therefore, ADC measurements may be a sensitive indicator of the severity
      of ischemic lesions.

PMID- 12500280
TI  - Proton spin-lock ratio imaging for quantitation of glycosaminoglycans in
      articular cartilage.
AB  - PURPOSE: To quantify glycosaminoglycans (GAG) in intact bovine patellar cartilage
      using the proton spin-lock ratio imaging method. This approach exploits spin
      lattice relaxation time in the rotating frame (T(1rho)) imaging and T(1rho)
      relaxivity (R(1rho)). MATERIALS AND METHODS: All the magnetic resonance imaging
      (MRI) experiments were performed on a 4-T whole-body GE Signa scanner (GEMS,
      Milwaukee, WI), and spectroscopy experiments of chondroitin sulfate (CS) phantoms
      were done on a 2-T custom-built spectrometer. A custom-built 11-cm-diameter
      transmit-receive birdcage coil, which was tuned to a proton frequency of 170 MHz,
      was employed for the imaging experiments. T(1rho) measurements were made using a
      fast spin echo (FSE) sequence pre-encoded with a three-pulse cluster consisting
      of two 90 degrees hard pulses separated by a low-power rectangle pulse for spin
      locking. RESULTS: The methodology is first validated on CS phantoms and then used
      to quantify GAG content in intact bovine cartilage (N = 5). There is a good
      agreement between the GAG map calculated from the T(1rho) ratio imaging method
      (71 +/- 4%) and GAG measured from spectrophotometric assay (75 +/- 5%) in intact
      bovine tissue. CONCLUSION: We have demonstrated a proton spin-lock ratio imaging
      method to quantify absolute GAG distribution in the cartilage in a noninvasive
      and nondestructive manner.

PMID- 12500281
TI  - Knees of Ironman triathletes: magnetic resonance imaging assessment of older (>35
      years old) competitors.
AB  - PURPOSE: To use magnetic resonance imaging (MRI) to evaluate the knees of older
      (>35 years old), competitive Ironman triathletes to determine the prevalence of
      abnormal findings. MATERIALS AND METHODS: The knees of 29 Ironman triathletes (20
      men, 9 women; age range, 35-66 years old) were studied by MRI. The findings were
      analyzed collectively and categorized into group I (N = 13), subjects without
      prior knee injuries and symptoms, and group II (N = 16), subjects with prior knee
      injuries and/or current symptoms. RESULTS: Ten percent of the knees had
      ligamentous abnormalities, but the prevalence was not statistically different
      comparing group I to group II. Fifty-five percent had abnormal menisci. The
      overall prevalence of abnormal menisci was significantly higher in group II (69%)
      than in group I (38%, P < 0.05). Cartilage abnormalities were found in 21% of the
      triathletes with a higher prevalence in group II (31%) than in group I (8%, P <
      0.05). Twenty-one percent (6/29) of the knees had bone contusions, with a higher
      prevalence in group II (31%) than in group I (8%, P < 0.05). CONCLUSION: In
      general, the spectrum of abnormal MRI findings of the knee was no greater than
      age-related changes previously reported for other athletic populations and
      nonathletes. These results have important implications for the diagnostic use of
      MRI of the knee in this high-endurance, athletic population.

PMID- 12500282
TI  - Diffusion-weighted MRI after cryosurgery of the canine prostate. Magnetic
      resonance imaging.
AB  - PURPOSE: To evaluate the acute lesion created by cryosurgery with diffusion
      weighted magnetic resonance imaging (DWI). MATERIALS AND METHODS: The appearance
      of the acute cryolesion was evaluated in four canine prostates DWI after they
      were warmed to original body temperature. The prostates were excised, stained
      with triphenyl tetrazolium chloride (TTC), photographed, prepared for hematoxylin
      and eosin (H&E) staining, and examined under a light microscope. RESULTS: A
      marked decrease in apparent diffusion coefficient of 38% was evident in the
      center of the previously frozen tissue, but not in all of the previously frozen
      tissue. Histologic results confirm differences between the iceball core and the
      periphery of the iceball, which have markedly different imaging characteristics
      on DWI. CONCLUSION: The core of the previously frozen tissue has a reduced
      apparent diffusion coefficient (ADC) compared to the periphery of the previously
      frozen tissue and previously unfrozen tissue.

PMID- 12500283
TI  - MRI/MRS evaluation of cariporide in a canine long-term model of reperfused
      ischemic insults. Magnetic resonance imaging/magnetic resonance spectroscopy.
AB  - PURPOSE: To examine with magnetic resonance imaging (MRI)/magnetic resonance
      spectroscopy (MRS) the long-term effects of cariporide in a canine cardiac
      ischemia/reperfusion model. MATERIALS AND METHODS: Twenty-two beagles underwent a
      2-hour occlusion followed by 10 days of reperfusion. Cine MRI and (31)P MRS were
      performed to monitor function and metabolism of the heart in the control (N = 10)
      and cariporide (N = 12) groups. Radioactively labeled microspheres were injected
      to determine coronary blood flow, and contrast-enhanced ex vivo MRI assessed
      infarct volumes. RESULTS: Cariporide produced a significant reduction vs.
      controls, in intracellular pH, during ischemia (P < 0.05) and at days 3 and 10
      postreperfusion (P < 0.0005). Functional recovery of the myocardium was
      significantly improved immediately upon reperfusion (percent of baseline: 63.5%
      +/- 3.5% for controls, 90.5% +/- 7.2% for cariporide) and at day 3, but not by
      day 10. Normalized infarct ratios (IRs) were similar for controls and cariporide
      (0.58 +/- 0.08, 0.58 +/- 0.06, respectively). CONCLUSION: Cariporide augments
      early functional recovery, while delaying normalization of intracellular pH
      following ischemia/reperfusion, but confers neither long-term functional or
      metabolic protection nor, most importantly, myocardial salvage.

PMID- 12500284
TI  - MR tagging of human lungs using hyperpolarized 3He gas.
AB  - PURPOSE: To evaluate the use of spin-tagging in conjunction with hyperpolarized
      gas imaging for monitoring lung ventilation and gas diffusion. METHODS AND
      MATERIALS: Images were taken at 0.15 T using single shot RARE, with
      hyperpolarized (3)He gas prepared by the metastability exchange technique.
      Sinusoidal modulation of the longitudinal magnetization (tag) was produced by two
      90-degree rf pulses separated by a gradient pulse. The diffusion of (3)He gas in
      the lungs was measured by monitoring the decay of the tags. This study was
      conducted on a 25-year-old, male, healthy volunteer. RESULTS: Clear tags in
      hyperpolarized (3)He gas both in vivo and in vitro were generated. The relative
      movement of the lung compared to a static, partial breath-hold was measured
      following inspiration or expiration. The diffusion coefficient of (3)He in the
      lungs was found to be 0.02 +/- 0.005 cm(2)seconds(-1). CONCLUSION: The spin
      tagging of hyperpolarized (3)He in the lungs is possible, and allows regional
      lung movements to be measured following inspiration and expiration. It also
      allows quantification of the diffusion of the (3)He gas.

PMID- 12500285
TI  - In vivo assessment of absolute perfusion in the murine skeletal muscle with spin
      labeling MRI. Magnetic resonance imaging.
AB  - PURPOSE: To assess absolute perfusion in the skeletal muscle of mice in vivo with
      spin labeling magnetic resonance imaging (MRI) under normal and stress
      conditions. MATERIALS AND METHODS: Absolute perfusion in the skeletal muscle of
      27 C57BL/6 mice was assessed in vivo non-invasively by spin labeling MRI at 7.05
      T. This technique was based on the acquisition of T1 maps with global and slice
      selective spin inversion in separate acquisitions. T1 mapping was performed by
      inversion recovery snapshot fast low angle shot imaging. To guarantee proper spin
      inversion within the whole mouse, a dedicated radiofrequency (RF) coil
      combination was constructed. A birdcage resonator was used for transmission,
      while detection of the MRI signal was achieved by a surface coil. RESULTS: Basal
      perfusion in the hindlimbs was determined to be 94 +/- 10 mL (100 g x minute)(-1)
      (mean +/- standard error of the mean [SEM], N = 27). This value is in good
      agreement with perfusion values determined by invasive techniques such as
      microspheres. A subgroup of six animals received a constant dose of 4 mg (kg x
      minute)(-1) of the vasodilator adenosine by an intraperitoneal catheter. In this
      case, perfusion was significantly increased to 179 +/- 56 mL (100 g x minute)(-1)
      (mean +/- SEM, N = 6, P < 0.02). Mean basal perfusion in this subgroup was 96 +/-
      26 mL (100 g x minute)(-1). CONCLUSION: Spin labeling MRI is a well-suited
      technique for the in vivo assessment of absolute perfusion in the murine skeletal
      muscle.

PMID- 12500286
TI  - Abnormal angiogenesis in diabetes mellitus.
AB  - The adverse long-term effects of diabetes mellitus have been well described and
      involve many organ systems. While diabetes management has largely focused on
      control of hyperglycemia, the presence of abnormalities of angiogenesis may cause
      or contribute to many of the clinical manifestations of diabetes. When compared
      with non-diabetic subjects, diabetics demonstrate vascular abnormalities of the
      retina, kidneys, and fetus. Diabetics have impaired wound healing, increased risk
      of rejection of transplanted organs, and impaired formation of coronary
      collaterals. In each of these conditions, and possibly in diabetic neuropathy as
      well, abnormalities of angiogenesis can be implicated in the pathogenesis. A
      perplexing feature of the aberrant angiogenesis is that excessive and
      insufficient angiogenesis can occur in different organs in the same individual.
      In this review, the clinical features, molecular mechanisms, and potential
      therapeutic options of abnormal angiogenesis in diabetes will be reviewed.

PMID- 12500287
TI  - Carbonic anhydrase inhibitors.
AB  - At least 14 different carbonic anhydrase (CA, EC 4.2.1.1) isoforms were isolated
      in higher vertebrates, where these zinc enzymes play crucial physiological roles.
      Some of these isozymes are cytosolic (CA I, CA II, CA III, CA VII), others are
      membrane-bound (CA IV, CA IX, CA XII, and CA XIV), CA V is mitochondrial and CA
      VI is secreted in saliva. Three acatalytic forms are also known, which are
      denominated CA related proteins (CARP), CARP VIII, CARP X, and CARP XI. Several
      important physiological and physio-pathological functions are played by many CA
      isozymes, which are strongly inhibited by aromatic and heterocyclic sulfonamides
      as well as inorganic, metal complexing anions. The catalytic and inhibition
      mechanisms of these enzymes are understood in detail, and this helped the design
      of potent inhibitors, some of which possess important clinical applications. The
      use of such enzyme inhibitors as antiglaucoma drugs will be discussed in detail,
      together with the recent developments that led to isozyme-specific and organ
      selective inhibitors. A recent discovery is connected with the involvement of CAs
      and their sulfonamide inhibitors in cancer: several potent sulfonamide inhibitors
      inhibited the growth of a multitude of tumor cells in vitro and in vivo, thus
      constituting interesting leads for developing novel antitumor therapies.
      Furthermore, some other classes of compounds that interact with CAs have recently
      been discovered, some of which possess modified sulfonamide or hydroxamate
      moieties. Some sulfonamides have also applications as diagnostic tools, in PET
      and MRI or as antiepileptics or for the treatment of other neurological
      disorders. Future prospects for drug design applications for inhibitors of these
      ubiquitous enzymes are also discussed.

PMID- 12500288
TI  - alphav Vitronectin receptors in vascular-mediated disorders.
AB  - Various integrin antagonist candidates including antibodies, cyclic peptides,
      peptidomimetics, and non-peptides have been clinically evaluated and shown to
      successfully modulate certain disease processes. This review will focus on the
      key role of the alphav integrin (alphavbeta3 and alphavbeta5) in vascular
      disorders such as restenosis and angiogenesis-mediated disorders.

PMID- 12500289
TI  - Polymethylene tetraamine backbone as template for the development of biologically
      active polyamines.
AB  - The concept that polyamines may represent a universal template in the receptor
      recognition process is embodied in the design of ligands for different biological
      targets. As a matter of fact, the insertion of different pharmacophores onto the
      polymethylene tetraamine backbone can tune both affinity and selectivity for any
      given receptor. The application of this approach provided a prospect of modifying
      benextramine (1). structure to achieve specific recognition of muscarinic
      receptors that led to the discovery of methoctramine (2). which is widely used as
      a pharmacological tool for muscarinic receptor characterization. In turn,
      appropriate structural modifications performed on the structure of methoctramine
      led to the discovery of new polyamines endowed with high affinity and selectivity
      for (a). muscarinic receptor subtypes, (b). G(i) proteins, and (c). muscle-type
      nicotinic receptors. Thus, polyamines tripitramine (9) and spirotramine (33),
      among others, were designed, which were shown to be highly selective for
      muscarinic M(2) and M(1) receptors, respectively. Several polyamines have been
      discovered, which inhibit noncompetitively a closed state of the nicotinic
      receptor. These ligands, such as 66, resulted in important tools for elucidating
      the mode and site of interaction of polyamines with the ion channel. It was
      discovered that reducing the flexibility of the diaminohexane spacer of
      methoctramine led to polyamines, such as 70, which are endowed with a biological
      profile significantly different from that of the prototype. Most likely,
      tetraamine (70) is a potent activator of G(i) proteins. Finally, the universal
      template approach formed the basis for modifying benextramine (1) structure to
      the design of ligands, which display affinity for acetylcholinesterase and
      muscarinic M(2) receptors. Thus, these polyamines, such as caproctamine (78),
      could have potential in the investigation of Alzheimer disease.

PMID- 12500290
TI  - Marine pyridoacridine alkaloids and synthetic analogues as antitumor agents.
AB  - Pyrido[4,3,2-mn]acridines are of major interest as metabolites in sponges and
      ascidians. During the last few years, numerous additional compounds of this
      family were isolated, some of them being polycyclic structures already reported
      with different substituents (shermilamine or kuanoniamine-derivatives), others,
      such as neoamphimedine, arnoamines and styelsamines having original structures.
      The synthesis of these compounds and analogues have been performed in order to
      allow their biological evaluation. In most of the cases, the cytotoxicity of
      analogues was improved compared to the natural product, specially in ascididemin
      or meridine series. The pyridoacridines have not a sole mode of action, but it
      seems that the reductive DNA cleavage mediated by reactive oxygen species is a
      potential general mode of action.

PMID- 12500291
TI  - Human B cells express a CD45 isoform that is similar to murine B220 and is
      downregulated with acquisition of the memory B-cell marker CD27.
AB  - BACKGROUND: Differences between human and murine B cells exist at all stages of B
      cell development, including the stage of memory B-cell formation. B cells in mice
      are identified with the pan-B-cell-specific CD45 isoform, B220. In initial
      studies in humans, it appeared that B220 expression did not include all B cells.
      This study was performed to expand on those preliminary findings. METHODS:
      Multiparameter flow cytometric detection of B220 expression on B cells was
      combined with a variety of B-cell markers. RESULTS: In contrast to mice, B220 was
      not a pan-B-cell marker in humans but was downregulated in the majority of B
      cells that acquired the human memory B-cell marker, CD27, whereas a minor memory
      B-cell subset remained B220(+), suggesting differences in differentiation.
      CONCLUSIONS: The B220 isoform in humans is developmentally regulated in humans,
      tied to the acquisition of a memory phenotype, and as such can be used as a
      differentiation-specific CD45 isoform, akin to the use of CD45 isoforms to
      distinguish between naive and memory T-cell subsets. Patients with
      immunodeficiency disorders, associated with defective memory B-cell generation
      and absent or reduced CD27(+) B cells, showed a corresponding lack of B220
      downregulation consistent with altered differentiation of B-cell subsets.

PMID- 12500292
TI  - CD87 as a marker for terminal granulocytic maturation: assessment of its
      expression during granulopoiesis.
AB  - BACKGROUND: Understanding the normal surface maturation pattern of granulocytes
      is essential for the recognition of abnormal patterns, which in turn may be of
      diagnostic or pathogenetic significance in disorders such as myelodysplastic
      syndromes and inherited bone marrow failure disorders. CD87 plays a role in
      cellular interaction, cell migration, and inflammatory response. Surface
      expression of this antigen has not been adequately studied on bone marrow
      granulocytes, and the small number of previous studies has provided conflicting
      data. METHODS: Bone marrow aspirates from 11 control subjects were studied by
      flow cytometry and a lysed whole blood technique to compare surface expression of
      CD87 on marrow granulocytes with those of CD11b, CD16, CD35, and CD10, which are
      expressed at the myelocyte, metamyelocyte, band, and segmented stage of
      neutrophilic development, respectively. Four sorting experiments of CD87(+)
      granulocytes were also performed. RESULTS: Our study showed no statistical
      difference between surface expression of CD35 and CD87 (P > 0.3), whereas
      significant differences existed between CD87 and the other antibodies (P <
      0.004). Sorting experiments showed that more than 80% of CD87(+) cells were bands
      and segmented neutrophils. Dual staining for CD87 and CD35 showed that most
      CD87(+) granulocytes coexpress CD35. CONCLUSIONS: CD87 is expressed on
      granulocytes at the band and segmented neutrophil stage of development and can be
      used to study normal and abnormal granulopoiesis.

PMID- 12500293
TI  - Numerical abnormalities of chromosomes 17 and 18 in sporadic colorectal cancer:
      Incidence and correlation with clinical and biological findings and the prognosis
      of the disease.
AB  - BACKGROUND: In recent years important information has accumulated on the genetic
      alterations present in colorectal tumors. However, thus far few studies have
      analyzed the impact of numerical abnormalities of chromosomes 17 and 18, which
      carry the p53 and DCC plus SHAD4/DPC4 genes involved in colorectal cancer, on the
      clinical and biological behaviors of the disease. METHODS: With the use of
      interphase fluorescence in situ hybridization (FISH), we analyzed the incidence
      of numerical abnormalities of chromosomes 17 and 18 in a series of malignant
      colorectal tumors and explored its potential association with clinicobiological
      behavior and the prognosis of the disease. For this purpose, 94 consecutive
      patients newly diagnosed with colorectal cancer were analyzed. In all cases, FISH
      analyses of the number of copies and nuclei of chromosomes 17 and 18 were
      performed in interphase nuclei with the use of double stainings. For all
      patients, information on age, sex, tumor size, Dukes' stage, tumor localization,
      DNA ploidy status, and the proportion of S-phase tumor cells was recorded. Median
      follow-up was 38 months. RESULTS: Numerical abnormalities of chromosomes 17 and
      18 were present in most patients with colorectal cancer (57% and 52%,
      respectively). Gains of chromosome 17 and monosomy 18 were found in 51% and 29%
      of cases, respectively, and they were the most frequent individual abnormalities
      for each chromosome. The simultaneous analysis of the number of copies of both
      chromosomes in the same cell showed that, in most cases displaying numerical
      abnormalities for these chromosomes, two or more different tumor cell clones were
      present. From a clinical point of view, numerical abnormalities of chromosome 17,
      especially monosomy 17, were associated with a significantly higher incidence of
      rectal tumors (P = 0.001) and Dukes' stage D (P = 0.02) and a lower median of
      disease-free survival among patients who underwent curative surgery (P = 0.05),
      as compared with diploid cases. In addition, cases with an altered number of
      copies of chromosome 17 showed a higher incidence of DNA aneuploidy (P = 0.0001)
      and a greater proportion of S-phase cells (P = 0.001) by flow cytometry. In
      contrast, no clear association was found between the presence of numerical
      abnormalities of chromosome 18 and clinicobiological disease characteristics,
      except for a higher incidence of DNA aneuploidy by flow cytometry (P = 0.001) and
      a lower median of disease-free survival (P = 0.06). Multivariate analysis showed
      that numerical abnormalities of chromosome 17, but not of chromosome 18, are an
      independent prognostic factor for predicting disease-free survival in patients
      with colorectal cancer. CONCLUSIONS: Numerical abnormalities of chromosomes 17
      and 18 were relatively common findings in patients with colorectal cancer, with
      chromosome 17 being associated with a higher incidence of tumors localized to the
      rectum and a worse clinical outcome. Cytometry Part B (Clin. Cytometry) 51B:14
      20, 2003.

PMID- 12500294
TI  - Investigations of phagosomes, mitochondria, and acidic granules in human
      neutrophils using fluorescent probes.
AB  - The oxidative burst is frequently evaluated by the conversion of dihydrorhodamine
      123 (DHR) to rhodamine 123 (R123) and hydroethidium (HE) to ethidium with the use
      of flow cytometry (FCM). Added R123 accumulates in mitochondria, but during
      phagocytosis R123 originating from DHR has been observed in neutrophil granules.
      The present study was designed to identify the site of reactive oxygen species
      (ROS) formation and the intracellular traffic of R123 in neutrophils by using
      mitochondrial membrane potential probes and the lysosomotropic probe LysoTracker
      Red, which have not previously been applied to neutrophils. Quiescent and
      phagocytosing human peripheral blood neutrophils were incubated with DHR, HE,
      R123, MitoTracker Green (MTG), MitoTracker Red (CMX-Ros), and LysoTracker Red
      alone and in all combinations of red and green probes, and studied by FCM and
      confocal laser scanning microscopy (CLSM). Phagosomes were filled with R123
      originating from DHR. Phagocytosis also triggered the oxidative burst in
      oxidative response granules that differed from acidic granules. All the
      neutrophils stained with mitochondrial and lysosomotropic dyes. Added R123 and
      MTG selectively accumulated in mitochondria. Added R123, MTG, and DHR increased
      the fluorescence of CMX-Ros and LysoTracker Red. This is the first FCM and CLSM
      demonstration of ROS formation in phagosomes. A distinct subpopulation of
      neutrophil granules, termed oxidative response granules, also was identified.
      Neutrophil mitochondrial membrane potential may be evaluated by incubating the
      cells with R123 and MTG, but results with CMX-Ros should be interpreted with
      caution. HE and DHR seem to measure a common pathway in the oxidative burst. The
      simultaneous application of several probes for investigations of organelles
      carries the risk of probe interference.

PMID- 12500295
TI  - Ethylenediaminetetraacetic acid plus citrate-theophylline-adenosine-dipyridamole
      (EDTA-CTAD): a novel anticoagulant for the flow cytometric assessment of platelet
      and neutrophil activation ex vivo in whole blood.
AB  - Ethylenediaminetetraacetic acid (EDTA) is the anticoagulant recommended for full
      blood counts, citrate is recommended for coagulation and platelet studies, and
      citrate-theophylline-adenosine-dipyridamole (CTAD) inhibits platelet activation.
      Because the combination of EDTA and CTAD (E/C) is better than EDTA or CTAD alone
      for measuring platelet parameters on the ADVIA 120 Haematology System, we
      investigated whether it also offers advantages for the flow cytometric assessment
      of platelet and/or neutrophil activation and platelet-leucocyte aggregate
      formation ex vivo. Blood from healthy subjects was collected into E/C or citrate,
      kept at room temperature or at 4 degrees C, and analysed 0 to 360 min later in
      the ADVIA 120 and by immunofluorescent flow cytometry. Platelet count, mean
      platelet volume, number of platelet clumps, mean platelet component, numbers of
      CD62P(+) platelets and platelet-leucocyte aggregates, and expression of CD11b on
      neutrophils changed little over 360 min in blood with E/C kept at 4 degrees C. In
      contrast, one or more parameter changed when blood was kept with E/C at ambient
      temperature or with citrate at either temperature. The use of E/C in in vitro and
      in vivo studies is illustrated. Platelet and neutrophil activation status ex vivo
      can be reliably assessed if blood is collected into E/C, held at 4 degrees C, and
      analysed within 6 h.

PMID- 12500296
TI  - Guess what: Chronic 13q14.3+/CD5-/CD23+ lymphocytic leukemia in blood and
      t(11;14)(q13;q32)+/CD5+/CD23- mantle cell lymphoma in lymph nodes!
AB  - We report a case of a patient with two B-cell lymphoproliferative disorders: CD5(
      )/CD23(+) B-cell chronic lymphocytic leukemia and CD5(+)/CD23(-) mantle cell
      lymphoma. These disorders were diagnosed simultaneously based on flow cytometry,
      immunohistochemistry, fluorescence in situ hybridization, and polymerase chain
      reaction-based molecular studies. The B-cell lymphocytic leukemia clone
      predominated in the blood and bone marrow, whereas the mantle cell clone
      predominated in lymph nodes.

PMID- 12500297
TI  - Detection of CD16low neutrophil subpopulations.

PMID- 12500299
TI  - Assessment of tumor cell repopulation after chemotherapy for advanced ovarian
      cancer: pilot study.
AB  - BACKGROUND: Repopulation of clonogenic tumor cells appears to increase during
      fractionated radiation treatment and is recognized as an important factor
      affecting local control. Given the longer intervals between cycles and longer
      total duration of treatment, the impact of repopulation is likely to be greater
      after chemotherapy. METHODS: We assessed tumor cell repopulation with the
      proliferative marker Ki-67 in 21 patients with ovarian carcinoma who received
      initial chemotherapy. Paraffin slides were evaluated from the diagnostic biopsy
      and from tumor obtained at debulking surgery after chemotherapy.
      Immunohistochemistry using the MIB-1 antibody was performed on the paired samples
      and analyzed with a digital imaging device linked to a color camera mounted on a
      transmitted-light microscope. The ratio of Ki-67 positive to all nuclei was used
      as a proliferative index and compared for pre- and postchemotherapy specimens.
      RESULTS: All patients received platinum-based chemotherapy and most showed a
      response to treatment. The median duration between last chemotherapy and
      debulking surgery was 33 days (range, 22-50 days). Four (19%) of 21 patients
      showed an increased proliferative index after chemotherapy, and the remainder
      showed a decrease (n = 12) or no significant change (n = 5). CONCLUSIONS: Our
      results did not suggest an increase in proliferation of tumor cells after this
      type of chemotherapy in the majority of patients with ovarian cancer.

PMID- 12500300
TI  - Phagocytosis of apoptotic cells by human macrophages: analysis by multiparameter
      flow cytometry.
AB  - BACKGROUND: Phagocytic removal of apoptotic cells is an important regulatory
      event in development, tissue homoeostasis, and inflammation. There are several
      methodologic problems with most in vitro studies of the molecular mechanisms of
      apoptotic cell phagocytosis. First, cell loss occurs during rigorous washing of
      adherent macrophages required to ensure removal of noningested particles. Second,
      discrimination of adherent or internalised apoptotic cells is difficult. Third,
      microscopic quantification is time consuming and has the potential for
      significant interobserver error. Fourth, subsequent analysis of phagocyte
      populations is difficult. METHODS: We used a flow cytometric method that allows
      quantification of phagocytosis of fluorescently labelled apoptotic cells with the
      use of multiparameter flow cytometric analysis. RESULTS: Phagocytosis of
      apoptotic cells was validated by use of inhibitors (cytochalasins) or low
      temperature and counterstaining with cell surface markers for the phagocytic
      targets to exclude binding to the phagocytic surface. Populations of phagocytic
      macrophages were sorted, and the presence of internalized apoptotic material was
      validated by microscopy. CONCLUSIONS: The technique we used in this study allows
      observer-independent analysis of phagocytosis of apoptotic cells by macrophages.
      Importantly, phagocytic or nonphagocytic populations could be subjected to
      further characterization with the use of flow cytometry with additional
      fluorochrome reagents and can be re-cultured to study underlying regulatory
      mechanisms.

PMID- 12500301
TI  - Evaluation of fluorescent dyes for measuring intracellular glutathione content in
      primary cultures of human neurons and neuroblastoma SH-SY5Y.
AB  - BACKGROUND: Reduced glutathione (GSH) protects cells against oxidative injury and
      maintains a range of vital functions. To study GSH content in human neuronal cell
      cultures, thiol-sensitive fluorescent techniques requiring a small number of
      cells may be of great value, but their GSH specificity has not been established
      in these cells. METHODS: We tested the efficiency of four currently available GSH
      fluorescent stains in human neurons and SH-SY5Y neuroblastoma cells, both
      cultured in microwells, by using a fluorescence plate reader. Cultures were
      treated with the inhibitor of the GSH synthesis, buthionine sulfoximine (BSO),
      and progressive GSH depletion was assayed with monochlorobimane (mBCl),
      monobromobimane (mBBr), 5-chloromethylfluorescein diacetate (CMFDA), and 7-amino
      4-chloromethylcoumarin (CMAC). GSH was also determined by a biochemical method in
      cell homogenates to obtain quantitative reference values. RESULTS: Neurons and SH
      SY5Y neuroblastoma had basal GSH contents of 27.1 +/- 3.2 and 14.5 +/- 1.7
      nmol/mg protein (n = 5), respectively. An approximate 90% depletion of GSH was
      obtained after 3 days of exposure to 1,000 microM of BSO in neurons and after 1
      day in SH-SY5Y cells. Cell death through an apoptotic pathway appeared 1-2 days
      after total GSH depletion. The assayed stains had different degrees of background
      fluorescence and sensitivity to GSH content, with similar results in both
      neuronal cell types. The probes mBCl and CMAC showed the lowest background, and
      the GSH-depletion curves were most similar to that of the reference method.
      CONCLUSIONS: Both mBCl and CMAC are useful fluorescent stains to determine
      semiquantitative GSH concentration in human neuronal cell cultures.

PMID- 12500302
TI  - Miniaturizing the comet assay with 3D vertical comets.
AB  - BACKGROUND: The comet or single-cell gel electrophoresis assay is a sensitive
      method for the detection of DNA damage. The main drawback of comet sampling is
      the low cell density necessary to prevent nucleus overlap after electrophoresis,
      which limits large-scale high throughput screening. Another problem may be
      inconsistent comet focusing. We investigated whether an approach based on three
      dimensional (3D) confocal microscopy might be beneficial for these concerns.
      METHODS: A vertical comet assay enabling three-dimensional confocal comet imaging
      of nuclei seeded at very high density was developed together with dedicated
      software algorithms to retrieve quantitative data at the single cell level.
      RESULTS: Three-dimensional confocal comet imaging greatly relieved the user
      interactions of our nonautomated two-dimensional comet sampling procedure.
      Batches of comets were blindly sampled, and confocal sectioning improved the
      clarity of the images and the accuracy of comet sampling. A 1-Gy dose response
      was readily established. The sampling speed was competitive with that of
      commercial packages. CONCLUSIONS: Vertical comet imaging is a new concept for
      fast and user-friendly comet sampling that allows miniaturization of the assay.
      It may become an essential step toward high throughput screening and exploit the
      benefits of confocal imaging.

PMID- 12500303
TI  - Evaluation of SDF-1/CXCR4-induced Ca2+ signaling by fluorometric imaging plate
      reader (FLIPR) and flow cytometry.
AB  - BACKGROUND: The chemokine receptors CXCR4 and CCR5 are the main coreceptors for
      human immunodeficiency virus (HIV) 1 to enter its target cells. The antiviral
      activity of their natural ligands (stromal cell-derived factor 1 [SDF-1],
      regulated on activation normal T-cell expressed and secreted, (RANTES) and
      macrophage inflammatory proteins 1alpha and 1beta, MIP-1alpha and MIP-1beta) and
      the finding that individuals deficient in CCR5 are relatively resistant to HIV
      infection led to the concept that chemokine receptor antagonists can play an
      important role in anti-HIV therapy. AMD3100, the prototype compound of the
      bicyclams, is one of the most potent and selective CXCR4 antagonists described to
      date. The search for new chemokine receptor antagonists involves the evaluation
      of compounds for their ability to block the specific chemokine-induced transient
      intracellular Ca(2+) flux. We evaluated two cell-based-fluorescent methods with
      the use of the Fluorometric Imaging Plate Reader (FLIPR) system and a flow
      cytometric assay to measure the SDF-1-induced intracellular Ca(2+) mobilization
      via CXCR4. Both assay systems were compared for their sensitivity, advantages,
      and system-dependent limitations. METHODS: CXCR4(+) lymphocytic and monocytic
      cell lines commonly used in laboratories studying acquired immunodeficiency
      syndrome and freshly isolated peripheral blood mononuclear cells (PBMCs) were
      loaded with the Ca(2+) indicator Fluo-3. After washing, the cells were
      preincubated with the CXCR4 antagonist AMD3100. Then the increase in
      intracellular Ca(2+) concentration after stimulation with SDF-1 was examined by
      the FLIPR and the flow cytometer, which monitored the change in green
      fluorescence intensity of Ca(2+)-bound Fluo-3. Surface CXCR4 expression was also
      determined flow cytometrically. RESULTS: In all five CXCR4(+) cell lines, SDF-1
      elicited a transient increase in intracellular Ca(2+) concentration. For each
      cell line, the magnitude of response was related to the level of CXCR4
      expression: the cells with the highest CXCR4 level showed the strongest Ca(2+)
      response. AMD3100 effected a dose-dependent inhibition of the SDF-1-induced
      Ca(2+) flux in all cell lines examined. The FLIPR was more sensitive than the
      flow cytometer in detecting minor Ca(2+) responses. In freshly isolated PBMCs,
      the Ca(2+) response was due solely to the stimulation of monocytes and
      granulocytes, whereas the lymphocyte population, although expressing CXCR4, did
      not respond at all. This phenomenon could be observed with the flow cytometer and
      not with the FLIPR. CONCLUSIONS: The FLIPR system is a most adequate to monitor
      intracellular Ca(2+) mobilization and to evaluate chemokine receptor antagonists.
      However, flow cytometry and its multiparameter analysis allow additional
      characterization of the cells involved in the chemokine receptor-mediated signal
      transduction.

PMID- 12500304
TI  - A new method for improving metaphase chromosome spreading.
AB  - BACKGROUND: The success of complex molecular cytogenetic studies depends on
      having properly spread chromosomes. However, inconsistency of optimum chromosome
      spreading remains a major problem in cytogenetic studies. METHODS: The metaphase
      spreading process was carefully timed to identify the most critical phase of
      chromosome spreading. The effects of dropping height of cell suspension, slide
      condition, drying time, fixative ratio, and relative humidity on the quality of
      metaphase spreads were studied by quantitative examination of metaphase
      chromosome spreads. Normal and immortalized human epithelial ovarian cells,
      neuroblastoma cells, and normal lymphocytes were tested. RESULTS: Humidity over
      the slide was the most important variable affecting the quality of chromosome
      spreads. Consistent improvement in chromosome spreading (larger metaphase area,
      less chromosome overlaps, or lower frequencies of broken metaphases) was obtained
      for all cell types if dynamic cell rehydration, occurring as fixative absorbs
      moisture from air, was made to coincide with the prompt fixation of spread
      chromosomes to the slide. This was achieved by dropping cells on dry glass slides
      placed in a shallow metal tray and then quickly lowering the tray into a covered
      50 degrees C water bath for slide drying. CONCLUSIONS: A new and simple method
      for improving metaphase chromosome spreading was developed based on our study on
      the characteristics of chromosome spreading.

PMID- 12500305
TI  - 9-Aminoacridine: an efficient reagent to improve human and plant chromosome
      banding patterns and to standardize chromosome image analysis.
AB  - BACKGROUND: Successful automated chromosome analysis requires the development of
      new techniques to increase and standardize chromosome length and improve banding
      patterns. METHODS: Human and plant cells were pretreated with the DNA
      intercalator 9-aminoacridine (9-AMA), and chromosomes were stained with GTG and
      aceto-orcein banding techniques and investigated by an image analysis system.
      RESULTS: The human optimal chromosome spreads with the 850 G-band resolution
      level, suitable for image analysis, were obtained by 9-AMA pretreatment for 1 h
      at a final concentration of 0.5-1 microg/ml, as compared with 600-700 bands after
      ethidium bromide treatment and about 400 bands without pretreatment. The best
      results for plant chromosomes were obtained after pretreatment with 1-2 microg/ml
      of 9-AMA for 12-24 h. The chromosomes elongated approximately 1.5-fold, and the
      resolution of chromosome banding patterns increased, reaching approximately 140
      bands per haploid set in the case of camomile. CONCLUSIONS: 9-AMA is an efficient
      reagent for the standardization and increasing the resolution of chromosome
      banding patterns in human and plant chromosomes. It is extremely important for
      chromosome investigation in small plants.

PMID- 12500307
TI  - Involvement of numb in vertebrate retinal development: evidence for multiple
      roles of numb in neural differentiation and maturation.
AB  - Cell fate specification is regulated in part by lateral inhibition mediated by
      Notch signaling. Notch signaling is negatively regulated by Numb, an intrinsic
      factor that regulates cellular competence. In this study we have examined the
      involvement of Numb in retinal development, which has been shown to be influenced
      by Notch signaling. In the developing retina, Numb is asymmetrically distributed
      towards the ventricular and vitreal poles of different cells. Asymmetric
      localization is evident not only in mitotic cells but in postmitotic ganglion
      cells as well, suggesting that the subcellular distribution of Numb may play a
      role after cells have exited the cell cycle. This is supported by the expression
      of Numb in terminally differentiated neurons in the adult retina. Although Numb
      is an intrinsic factor, it is observed that its subcellular distribution is
      influenced by epigenetic cues such that a higher proportion of cells cultured at
      high density express Numb asymmetrically. A correlation is observed between
      asymmetric localization and cellular competence; cells in which Numb is
      asymmetric differentiate more readily in culture than those that express Numb
      symmetrically. We have identified alternative splice variants in the developing
      and adult retina that correspond to isoforms that have been shown to regulate
      proliferation and differentiation. The dynamic temporal expression patterns of
      alternative splice variants and isoforms suggest that Numb may influence
      proliferation and differentiation of retinal progenitors during neurogenesis and
      maturation of postmitotic neurons. Together, these results demonstrate the
      complex role of the distribution of Numb within progenitors and postmitotic
      neurons.

PMID- 12500308
TI  - Distribution of GluR1 is altered in the olfactory bulb following neonatal naris
      occlusion.
AB  - The olfactory system is well suited for studies of glutamate receptor plasticity.
      The sensory neurons are glutamatergic, and they turn over throughout life, and
      the olfactory bulb neurons that process their inputs express many of the known
      glutamate receptor subunits. Neonatal naris occlusion alters olfactory bulb
      development and the expression of certain neuroactive substances and receptors,
      at least in part due to loss of the sensory inputs. We therefore postulated that
      neonatal naris occlusion might alter glutamate receptor expression during
      postnatal development. Single nares of newborn mice were occluded on postnatal
      days 1-2, and the distribution of glutamate receptor subunits was evaluated using
      immunoperoxidase methods. Light microscopic examination on postnatal day 6 failed
      to reveal adult-like staining of neuronal cell bodies in the olfactory bulbs. By
      day 12, cell bodies that were immunoreactive (-IR) for the GluR1 subunit were
      visible in the external plexiform layer (EPL) of both sides. By day 18, many of
      the GluR1-IR cell bodies could be identified as cell types that had previously
      been reported to express homomeric GluR1 receptors. Analysis of single, mid
      dorsal sections from 18-25-day-old mice showed that the medial EPL of the
      occluded side had a significantly lower density of these cell bodies. The GluR1
      staining of the adjacent mitral cell layer (MCL) was also heavier on the occluded
      side, but no gross differences in staining for other glutamate receptor subunits
      were observed. Neonatal naris occlusion therefore appears to provide a new model
      for studying expression of GluR1 receptors during the development of a discrete
      population of olfactory bulb neurons.

PMID- 12500309
TI  - Effect of reduced impulse activity on the development of identified motor
      terminals in Drosophila larvae.
AB  - In Drosophila larvae, motoneurons show distinctive differences in the size of
      their synaptic boutons; that is, axon 1 has type Ib ("big" boutons) terminals and
      axon 2 has type Is ("small" boutons) terminals on muscle fibers 6 and 7. To
      determine whether axon 1 develops large boutons due to its high impulse activity,
      we reduced impulse activity and examined the motor terminals formed by axon 1.
      The number of functional Na(+) channels was reduced either with the nap(ts)
      mutation or by adding tetrodotoxin (TTX) to the media (0.1 microg/g). In both
      cases, the rate of locomotion was decreased by approximately 40%, presumably
      reflecting a decrease in impulse activity. Locomotor activity was restored to
      above wild-type (Canton-S) levels when nap(ts) was combined with a duplication of
      para, the Na(+)-channel gene. Lucifer yellow was injected into the axon 1 motor
      terminals, and we measured motor terminal area, length, the number of branches,
      and the number and width of synaptic boutons. Although all parameters were
      smaller in nap(ts) and TTX-treated larvae compared to wild-type, most of these
      differences were not significant when the differences in muscle fiber size were
      factored out. Only bouton width was significantly smaller in both different
      nap(ts) and TTX-treated larvae: boutons were about 20% smaller in nap(ts) and TTX
      treated larvae, and 20% larger in nap(ts); Dp para(+) compared to wild-type. In
      addition, terminal area was significantly smaller in nap(ts) compared to wild
      type. Bouton size at Ib terminals with reduced impulse activity was similar to
      that normally seen at Is terminals. Thus, differences in impulse activity play a
      major role in the differentiation of bouton size at Drosophila motor terminals.

PMID- 12500310
TI  - Lithium inhibits a late step in agrin-induced AChR aggregation.
AB  - Agrin activates an intracellular signaling pathway to induce the formation of
      postsynaptic specializations on muscle fibers. In myotubes in culture, this
      pathway has been shown to include autophosphorylation of the muscle-specific
      kinase MuSK, activation of Src-family kinases, tyrosine phosphorylation of the
      acetylcholine receptor (AChR) beta subunit, a decrease in receptor detergent
      extractability, and the accumulation of AChRs into high-density aggregates. Here
      we report that treating chick myotubes with lithium prevented any detectable
      agrin-induced change in AChR distribution without affecting the number of AChRs
      or the agrin-induced change in AChR tyrosine phosphorylation and detergent
      extractability. Lithium treatment also increased the rate at which AChR
      aggregates disappeared when agrin was removed. The effects of lithium developed
      slowly over the course of approximately 12 h. Thus, sensitivity to lithium
      identifies a late step in the agrin signaling pathway, after agrin-induced MuSK
      and AChR phosphorylation, that is necessary for the recruitment of AChRs into
      visible aggregates.

PMID- 12500311
TI  - Independent roles of Rho-GTPases in growth cone and axonal behavior.
AB  - Many external signals influence growth cone motility, pathfinding, and the
      formation of synapses that lead to the final map formation of the retinotectal
      system. Chick temporal retinal ganglion cell axons (RGCs) collapse and retract
      after encountering posterior tectal cells in vitro. During this process lateral
      extensions appear along the RGC axonal shaft. Lateral extensions appear as
      nascent interstitial axonal branches and also as defasciculating growth cones
      that are trailing along the pioneer axon. RGC branching controlled by repellent
      tectal cues has recently been shown to be the critical event in retinotectal map
      development. The intracellular mechanism underlying this phenomenon, however, is
      not understood. Inhibiting RhoA with either C3 toxin or inhibiting p160Rock
      kinase, an effector of RhoA, with Y27632 inhibited collapse, retraction, and the
      number of axons that showed lateral extensions. Lateral extension length
      increased significantly. Inhibiting Rac1A and cdc42 with cell permeable peptide
      inhibitors did not inhibit collapse of growth cones, but did inhibit axon
      retraction. In addition, the number of axons that showed lateral extensions and
      lateral extension length were significantly reduced. A dynamic cytoskeleton is
      necessary to react to incoming guidance information. This study addresses the
      problems of how growth cone motility and branching or defasciculation are
      affected by Rho-GTPases as extracellular signals are transmitted to the
      cytoskeleton.

PMID- 12500312
TI  - Aromatase inhibition affects testosterone-induced masculinization of song and the
      neural song system in female canaries.
AB  - Songbirds have a specialized steroid-sensitive network of brain nuclei, the song
      system, for controlling song. Most nuclei of the song system express androgen
      receptors, and the sensory-motor integration nucleus High Vocal Center (HVC)
      alone also expresses estrogen receptors. Apart from expressing estrogen receptors
      in the vocal control system, songbirds are unique among birds because they have
      high concentrations of the estrogen-synthesizing enzyme aromatase in the
      neostriatum surrounding HVC. However, the role of estrogen in controlling the
      development of the song structure has been scarcely investigated. In this work,
      we show that blocking the production of estrogen during testosterone-induced song
      motor development in adult female canaries alters the song pattern compared to
      control females treated with testosterone only. These effects were correlated
      with inhibition of the expression of estrogen-sensitive genes, such as brain
      derived nerve growth factor, in HVC. The expression of the ATP-synthase gene, an
      indicator of cell activity, in HVC, and the size of HVC, were not affected by the
      treatment. Our results provide the first example of estrogen-sensitive mechanisms
      controlling the structural features of adult birdsong.

PMID- 12500313
TI  - Serotonin in the developing stomatogastric system of the lobster, Homarus
      americanus.
AB  - We studied the development of the serotonergic modulation of the stomatogastric
      nervous system of the lobster, Homarus americanus. Although the stomatogastric
      ganglion (STG) is present early in embryonic development, serotonin
      immunoreactivity is not visible in the STG until the second larval stage.
      However, incubation of the STG with exogenous serotonin showed that a serotonin
      transporter is present in embryonic and early larval stages. Serotonin uptake was
      blocked by paroxetine and 0% Na(+) saline. The presence of a serotonin
      transporter in the embryonic STG suggests that hormonally liberated serotonin
      could be taken up by the STG, and potentially released as a "borrowed
      transmitter". Consistent with a potential hormonal role, serotonin is found in
      the pericardial organs, a major neurosecretory structure, by midembryonic
      development. The rhythmic motor patterns produced by embryonic and larval STGs
      were decreased in frequency by serotonin. Lateral Pyloric (LP) neuron-evoked
      excitatory junctional potentials (EJPs) in the embryos and the first larval stage
      (LI) were larger, slower, and more variable than those in the adult. The
      amplitude of adult LP neuron-evoked EJPs was increased more than twofold in
      serotonin, but in embryos and LI preparations this effect was negligible. In
      embryos and LI preparations, serotonin increased the occurrence of muscle fiber
      action potentials and altered the EJP wave-form. These data demonstrate that
      serotonin receptors are present in the stomatogastric nervous system early in
      development, and suggest that the role of serotonin changes from modulation of
      muscle fiber excitability early in development to enhancement of neurally evoked
      EJPs in the adult.

PMID- 12500314
TI  - Cytoskeletal dynamics underlying collateral membrane protrusions induced by
      neurotrophins in cultured Xenopus embryonic neurons.
AB  - The establishment and refinement of neuronal connections depend on dynamic
      modification of the morphology and physiology of developing axons in response to
      extrinsic factors. In embryonic cultures of Xenopus spinal neurons, acute
      application of brain-derived neurotrophic factor (BDNF) induced rapid collateral
      protrusion of filopodium-like microspikes and lamellipodia along the neurite
      processes, leading to a morphologic alternation of the neuron. Both types of
      membrane protrusions contained high concentrations of actin filaments and
      depended on the polymerization of the actin cytoskeleton. Immunofluorescent
      staining, however, revealed the presence of microtubules (MTs) in lamellipodia
      induced by BDNF. These MTs appeared to have arisen from debundling of MTs in the
      neurite shaft at the protrusion sites, splaying and extending in the rapidly
      protruding lamellipodia. Inhibition of microtubule polymerization by nocodazole
      largely abolished the formation of lamellipodia but not of microspikes. Taken
      together, our results suggest that collateral sprouting of microspikes and
      lamellipodia involve distinctly different cytoskeletal mechanisms. Although the
      actin cytoskeleton is solely responsible for microspike formation, cooperative
      efforts by microtubules and actin filaments are essential for lamellipodial
      protrusion in response to extrinsic factors.

PMID- 12500315
TI  - Biogenic amines in the antennal lobes and the initiation and maintenance of
      foraging behavior in honey bees.
AB  - Previous findings showed that high levels of octopamine and serotonin in the
      antennal lobes of adult worker honey bees are associated with foraging behavior,
      and octopamine treatment induces precocious foraging. To better characterize the
      relationship between amines and foraging behavior in honey bees, we performed a
      detailed correlative analysis of amine levels in the antennal lobes as a function
      of various aspects of foraging behavior. Flight activity was measured under
      controlled conditions in a large outdoor flight cage. Levels of octopamine in the
      antennal lobes were found to be elevated immediately subsequent to the onset of
      foraging, but they did not change as a consequence of preforaging orientation
      flight activity, diurnal pauses in foraging, or different amounts of foraging
      experience, suggesting that octopamine helps to trigger and maintain the foraging
      behavioral state. In contrast, levels of serotonin and dopamine did not show
      changes that would implicate them as either causal agents of foraging, or as
      neurochemical systems affected by the act of foraging. Serotonin treatment had no
      effect on the likelihood of foraging. These results provide further support for
      the hypothesis that an increase in octopamine levels in the antennal lobes plays
      a causal role in the initiation and maintenance of the behavioral state of
      foraging, and thus is involved in the regulation of division of labor in honey
      bees.

PMID- 12500316
TI  - Museum collections--a cause for concern.

PMID- 12500317
TI  - Medicaid reform in the 1990s.

PMID- 12500318
TI  - Evolution of Medicaid managed care systems and eligibility expansions.

PMID- 12500319
TI  - "Second-generation" Medicaid managed care: can it deliver?
AB  - This article offers insight into what we term "second-generation" Medicaid
      managed care. In case studies of seven States, we examined three critical
      questions: (1) Does managed care experience facilitate program operations? (2)
      Can Medicaid managed care deliver on important goals? and (3) Can States extend
      the program beyond low-income families and children to others? The answers are
      encouraging but also suggest caution. Medicaid managed care is not a solution to
      fundamental problems facing the Medicaid program. It may be a tool to encourage
      better delivery of care. This requires a long-term commitment and adequate
      financing to develop stable partnerships with all stakeholders.

PMID- 12500320
TI  - Innovations in section 1115 demonstrations.
AB  - This article discusses how States have taken advantage of the flexibility
      afforded under section 1115 research and demonstration authority. It describes
      how States have used Section 1115 authority to develop innovations in outreach
      and enrollment, eligibility requirements, access, benefits, quality assurance,
      payment, safety net providers, and special needs populations. It concludes by
      discussing the future challenges that all the players in Medicaid demonstration
      projects are facing.

PMID- 12500321
TI  - Perils of pioneering: monitoring Medicaid managed care.
AB  - This article reviews Federal and State oversight of section 1115 Medicaid managed
      care demonstrations in Hawaii, Oklahoma, Rhode Island, and Tennessee from 1994 to
      1998. Under Medicaid managed care, the Federal Government and States have had to
      shift their focus and resources into oversight functions that barely existed in
      fee-for-service (FFS) Medicaid. We find that managed care monitoring was slow to
      begin and not always adequate in these demonstrations. While State and Federal
      monitoring have improved over time, monitoring is not yet at the point of
      ensuring access and quality.

PMID- 12500322
TI  - Medicaid's complex goals: challenges for managed care and behavioral health.
AB  - The Medicaid program has become increasingly complex as policymakers use it to
      address various policy objectives, leading to structural tensions that surface
      with Medicaid managed care. In this article, we illustrate this complexity by
      focusing on the experience of three States with behavioral health carveouts-
      Maryland, Oregon, and Tennessee. Converting to Medicaid managed care forces
      policymakers to confront Medicaid's competing policy objectives, multiplicity of
      stakeholders, and diverse patients, many with complex needs. Emerging Medicaid
      managed care systems typically represent compromises in which existing inequities
      and fragmentation are reconfigured rather than eliminated.

PMID- 12500323
TI  - Federally qualified health centers: surviving Medicaid managed care, but not
      thriving.
AB  - This article reviews the experiences of federally qualified health centers
      (FQHCs) in Hawaii, Rhode Island, and Tennessee before and after Medicaid managed
      care demonstrations began. Adapting to managed care proved challenging, but all
      FQHCs survived. Overall, FQHCs performed better financially than anticipated,
      partly because demonstrations expanded coverage to previously uninsured
      individuals, and because FQHCs in two States formed plans that paid FQHCs more
      than other plans. Service encounters declined; it is unclear if this is negative,
      since it may indicate more efficient care delivery. In some cases, supportive
      State policies aided FQHCs' survival. Continued adaptation is critical for FQHCs'
      longer term prospects.

PMID- 12500324
TI  - Covering uninsured adults through Medicaid: lessons from the Oregon health plan.
AB  - The Oregon Health Plan (OHP), Oregon's section 1115 Medicaid waiver program,
      expanded eligibility to all residents living below poverty. We use survey data,
      as well as OHP administrative data, to profile the expansion population and to
      provide lessons for other States considering such programs. OHP's eligibility
      expansion has proved a successful vehicle for covering large numbers of uninsured
      adults, although most beneficiaries enroll for only a brief period of time. The
      expansion population, particularly childless adults, is relatively sick and has
      high service use rates. Beneficiaries are also likely to enroll when they are in
      need of care.

PMID- 12500325
TI  - Reforming the Medicaid disproportionate share hospital program.
AB  - Since 1991, three Federal laws have sought to reform the Medicaid
      disproportionate share hospital (DSH) program, which is designed to help safety
      net hospitals. This article provides findings from a 40-State survey about
      Medicaid DSH and supplemental payment programs in 1997. Results indicate that the
      overall size of the DSH program did not grow from 1993 to 1997, but the
      composition of DSH revenues and expenditures changed substantially: A much higher
      share of the DSH funds were being paid to local hospitals and relatively less was
      being retained by the States. The study also revealed that large differences in
      States' use of DSH still persist.

PMID- 12500326
TI  - Medicaid 1915(c) home and community-based services waivers across the states.
AB  - This article provides State-level data on the Medicaid 1915(c) home and community
      based services (HCBS) waivers program. Medicaid 1915(c) waiver participants were
      32 percent of the Medicaid participants in institutional care in 1997. These data
      document wide interstate variation in organizational oversight and program
      policies for the waivers. Many structural barriers to HCBS waiver growth existed.
      Case management services, in some form, were normative for most HCBS waiver
      participants, but formal mechanisms to assess client satisfaction and service
      quality were less common. Substantial new growth in this program may require
      fundamental changes in HCBS waiver policies.

PMID- 12500327
TI  - Characteristics of Medicare persons in long-term care facilities.

PMID- 12500328
TI  - Information needs and preferences of the Medicare population with vision loss.

PMID- 12500329
TI  - HHS announces electronic standards to simplify health care transactions.

PMID- 12500330
TI  - Health status "snapshot" of U.S. counties now on Web.

PMID- 12500331
TI  - Strategies announced for halving smoking rates by 2010.

PMID- 12500332
TI  - Guidance issued for providers to ensure language assistance.

PMID- 12500333
TI  - APHA encourages adequate funding for Indian Health Service.

PMID- 12500334
TI  - Exercise caution in gene modification research, report urges.

PMID- 12500335
TI  - Long-term care hospitals under Medicare: facility-level characteristics.
AB  - Though accounting for only a small percentage of total Medicare spending, long
      term care hospitals (LTCHs) (defined as having an average length of stay [LOS] of
      25 days or more) have been growing, in number and in Medicare expenditures, at a
      rapid rate in recent years. Because they have not been widely studied, we
      conducted research to describe the characteristics of this increasingly important
      Medicare provider type. We found that most LTCHs specialize in the provision of
      respiratory care or rehabilitation. Information from this study can help inform
      the development of a Medicare prospective payment system for LTCHs.

PMID- 12500336
TI  - Premium rebates and the quiet consensus on market reform for Medicare.
AB  - Premium rebates allow beneficiaries who choose more efficient Medicare options to
      receive cash rebates, rather than extra benefits. That simple idea has been
      controversial. Without fanfare, however, premium rebates have become a key area
      of agreement in the debate on Medicare reform. Moreover, in legislation in late
      2000, it became official policy: Medicare+Choice (M+C) plans will be allowed to
      offer rebates beginning in 2003. This article explores the economic rationale for
      premium rebates, provides a historical perspective on the rebate debate,
      discusses some of the implementation issues that need to be addressed before
      2003, and reviews the implications of premium rebates for current legislative
      proposals for Medicare reform.

PMID- 12500337
TI  - Race and ethnicity and the identification of special needs children.
AB  - Increasingly, Medicaid and Title XXI Programs are using survey-based approaches
      to identify children with special health care needs (CSHCN) for quality assurance
      monitoring and program referrals. However, little work has been done examining
      how well instruments, like the Questionnaire for Identifying Children with
      Chronic Conditions and the CSHCN Screener, identify CSHCN among black and
      Hispanic families. Differences in item interpretation and in response styles
      could influence the identification of CSHCN from these groups. Our results
      suggest that children who are black or Hispanic with special health care needs
      may be underidentified relative to white or non-Hispanic children using currently
      available survey tools.

PMID- 12500338
TI  - Comorbidity-based payment methodology for Medicaid enrollees with HIV/AIDS.
AB  - Managed care organizations (MCOs) may be incurring financial losses from persons
      with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
      (AIDS) (PWHA). This study developed a statistical model to examine which specific
      comorbidities are important contributors to the variations in health care costs
      of PWHA. Individuals were classified into cost groups to simulate biased
      selection in MCOs. Capitation payments for various cost groups under different
      methodologies were compared. The statistical model closely matched payments with
      the actual costs of care. Capitation payments for HIV/AIDS enrollees based on
      this model will better protect MCOs than the traditional risk-adjustment methods.

PMID- 12500339
TI  - Financial performance and participation in Medicaid and Medi-Cal managed care.
AB  - This article assesses the participation and the financial performance of licensed
      health maintenance organization (HMOs) in the Medicaid market. The study found
      that participation by Medicaid Dominant plans has more than doubled from 11
      percent in 1992 to 23 percent in 1998 while Medicaid membership in Commercial
      Dominant plans declined from 71 percent in 1994 to 51 percent in 1998. Both
      participating and non-participating plans incurred operating losses in 1998. Medi
      Cal participating plans had higher operating margins than Medicaid participating
      plans throughout the United States. Interviews with key informants express
      concern about competence in program management, rate adequacy, decline in
      Medicaid enrollment, and turbulence forces of managed care market on Medicaid
      programs.

PMID- 12500340
TI  - Use of conventional antipsychotics and the cost of treating schizophrenia.
AB  - This study documents the drug therapy patterns and 1-year treatment costs for
      18,833 Medicaid patients with schizophrenia treated with conventional
      antipsychotic medications in Michigan, Kentucky, Alabama, and Georgia. One in
      four patients used no antipsychotic, but had total costs that were less than for
      treated patients (-$2,576, p < .0001); 18 percent of treated patients delayed
      therapy for at least 1 month and had significantly higher total costs of $3,994
      (p < .0001); 41 percent of treated patients changed therapy with similar results
      (+$4,067, p < .0001). Only 20 percent of patients were compliant with drug
      therapy but this had no significant impact on total treatment costs.

PMID- 12500341
TI  - Medicare spending increases more than 10 percent in 2001.

PMID- 12500342
TI  - Life expectancy hit new high in 2000.

PMID- 12500343
TI  - HHS proposes changes to further limit Medicaid loophole.

PMID- 12500344
TI  - CMS proposes physician fee payment changes for 2002.

PMID- 12500345
TI  - Changing nature of public and private health insurance.

PMID- 12500346
TI  - Insurance trends for the Medicare population, 1991-1999.

PMID- 12500347
TI  - Retiree health insurance: recent trends and tomorrow's prospects.
AB  - Using both employer- and beneficiary-level data, we examined trends in employer
      sponsored retiree health insurance and prospects for future coverage. We found
      that retiree health insurance has become less prevalent over the past decade,
      with firms reporting declines in the availability of coverage, and Medicare
      eligible retirees reporting lower rates of enrollment. The future of retiree
      health insurance is uncertain. The forces discouraging its growth--rising premium
      costs, a slower economy, judicial challenges, and an uncertain Medicare+Choice
      (M+C) program and policy agenda--far outweigh the forces likely to encourage
      expansion.

PMID- 12500348
TI  - Using Medicaid/SCHIP to insure working families: the Massachusetts experience.
AB  - Massachusetts was the first State to implement a premium subsidy program for
      employer-sponsored health insurance, using both Medicaid and State Children's
      Health Insurance Program (SCHIP) funding. The Insurance Partnership (IP) provides
      subsidies directly to small employers, and the Premium Assistance Program
      provides subsidies to their low-income employees. Approximately 3,500 small firms
      currently participate, most of them offering health insurance coverage for the
      first time. Approximately 10,000 adults and children are covered through the
      program, the majority of whom had been uninsured prior to enrolling.
      Massachusetts' successful experience with premium subsidies offers important
      lessons for other States wishing to implement similar programs.

PMID- 12500349
TI  - Disenrollment and re-enrollment patterns in a SCHIP.
AB  - This article examines the impact of four policy changes made to a State
      children's health insurance program (SCHIP) as it transitioned to Title XXI on
      program disenrollment and re-enrollment. The changes were: (1) expanded
      eligibility criteria, (2) reduction in the family share of the premium, (3)
      expansion of the mental health benefit, and (4) implementation of a 60-day wait
      period to re-enrollment in the program for children who involuntarily disenrolled
      due in non-payment of premium. Disenrollment was reduced by 20 percent after the
      changes were implemented. Disenrollment and re-enrollment rates varied
      significantly based on the child's health and family income.

PMID- 12500351
TI  - Home and community-based services in seven states.
AB  - As part of a CMS-funded study, case studies were conducted in Alabama, Indiana,
      Washington, Wisconsin, Maryland, Michigan, and Kentucky to assess the major
      features of the home and community-based services system for older people and
      younger adults with physical disabilities in each State. The case studies
      analyzed the financing of services; administrative systems; eligibility,
      assessment, and case management structures; the services provided, including
      consumer-directed home care and group residential care; cost-containment efforts;
      and quality assurance. The role that Medicaid plays in home and community-based
      services is a major focus of the study.

PMID- 12500350
TI  - Consequences of states' policies for SCHIP disenrollment.
AB  - Policymakers are concerned about disenrollment from the State Children's Health
      Insurance Program (SCHIP). We describe disenrollment in Florida, Kansas, New
      York, and Oregon and assess the links between disenrollment and States' SCHIP
      policies. We found that SCHIP is used on a long-term basis (at least 2 years) for
      a significant group of new enrollees and as temporary coverage (fewer than 12
      months) for many others. Recertification generates large disenrollments (about
      one-half of children still enrolled at the time), but as many as 25 percent
      return within 2 months. The increased disenrollment rate at recertification is
      completely eliminated by a policy of passive re-enrollment.

PMID- 12500352
TI  - Employment-related health insurance: federal agencies' roles in meeting data
      needs.
AB  - Employer-sponsored health insurance accounts for almost one-third of all health
      care spending. As health care cost growth accelerates affecting the availability
      of employer-sponsored insurance and depth of coverage, the importance of timely
      and accurate information for measuring and monitoring these changes and
      formulating policy options increases. Identifying a growing gap between the need
      for and availability of data to inform policy on employment-related health
      insurance issues, the Office of Management and Budget (OMB) established a
      committee of Federal agency representatives to evaluate and advise data
      collection efforts. This article reports on the committee's current efforts,
      focusing on evaluation of results from the Medical Expenditure Panel Survey
      Insurance Component (MEPS-IC) and the National Compensation Survey (NCS).

PMID- 12500353
TI  - Burden of health care costs: businesses, households, and governments, 1987-2000.
AB  - In this article, we estimate expenditures by businesses, households, and
      governments in providing financing for health care for 1987-2000 and track
      measures of burden that these costs impose. Although burden measures for
      businesses and the Federal Government have stabilized or improved since 1993,
      measures of burden for State and local governments are deteriorating slightly--a
      situation that is likely to worsen in the near future. As health care spending
      accelerates and an economy wide recession seems imminent, businesses, households,
      and governments that finance health care will face renewed health cost pressures
      on their revenue and income.

PMID- 12500354
TI  - Supplemental Insurance for Community Aged and Disabled Beneficiaries: 1999.

PMID- 12500355
TI  - HHS takes steps to further limit Medicaid loophole.

PMID- 12500356
TI  - Medicare to expand coverage of positron emission tomography.

PMID- 12500357
TI  - Medi-Cal program suffering physician shortages.

PMID- 12500358
TI  - CMS's consumer information efforts.

PMID- 12500359
TI  - Lessons learned from the National Medicare & You Education Program.
AB  - In fall 1998 CMS implemented the National Medicare Education Program (NMEP) to
      educate beneficiaries about their Medicare program benefits; health plan choices;
      supplemental health insurance; beneficiary rights, responsibilities, and
      protections; and health behaviors. CMS has been monitoring the implementation of
      the NMEP in six case study sites as well as monitoring each of the information
      channels for communicating with beneficiaries. This article describes select
      findings from the case studies, and highlights from assessment activities related
      to the Medicare & You handbook, the toll-free 1-800-MEDICARE Helpline, Internet,
      and Regional Education About Choices in Health (REACH).

PMID- 12500360
TI  - Beneficiaries' perceptions of new Medicare health plan choice print materials.
AB  - This article presents findings from a study involving seven focus groups with
      aged and disabled Medicare beneficiaries in the Kansas City area regarding their
      impressions of a pilot version of the Medicare & You 1999 handbook and the
      Medicare Consumer Assessment of Health Plans Study (CAHPS) survey report.
      Beneficiaries generally had positive reactions to both booklets and viewed the
      handbook as an important reference tool. Based on the findings, we present policy
      recommendations for the development and dissemination of Medicare health plan
      information to beneficiaries.

PMID- 12500361
TI  - Beneficiary survey-based feedback on new Medicare informational materials.
AB  - In response to the Balanced Budget Act (BBA) of 1997, the Center for Medicare &
      Medicaid Services (CMS) initiated a massive information and education campaign to
      promote effective health plan decision-making. Early results suggest that the
      pilot version of the Medicare & You handbook and other new Medicare informational
      materials were viewed favorably overall. Despite their limitations, most
      beneficiaries found the information useful. The longer, more comprehensive
      materials were not perceived to be more useful than the shorter, less complicated
      version. Additional research is needed to determine which subgroups of
      beneficiaries may need more and, possibly less, information.

PMID- 12500362
TI  - Measuring beneficiary knowledge in two randomized experiments.
AB  - This article reports results of two studies that measured beneficiaries'
      knowledge of the Medicare program and related health insurance options using pre-
      and post-experimental designs. Knowledge was measured using multiple item indexes
      before and after receiving new informational materials developed by the Centers
      for Medicare & Medicaid Services (CMS) as part of the National Medicare Education
      Program (NMEP). Beneficiaries in both studies showed statistically significant
      gains in knowledge after receiving the new materials. Policy implications for the
      measurement of knowledge and creation of future versions of the materials are
      discussed.

PMID- 12500363
TI  - Beneficiary decisionmaking: the impact of labeling health plan choices.
AB  - One critical health plan decision concerns choosing an original Medicare plan or
      a Medicare managed care plan. Evidence suggests that people are confused by the
      phrase "Original Medicare plan." Using focus group and Q-sort methodology, the
      authors sought to identify a name for the Medicare fee-for-service (FFS) product.
      Two key insights were gained. First, participants used the word "Medicare" to
      name the FFS product. Second, participants did not choose between two plans.
      Rather, they decided between supplemental insurance and a managed care product.
      These factors should influence how CMS "brands" not only the FFS product but also
      the overall Medicare program.

PMID- 12500364
TI  - Preventing medical errors: communicating a role for Medicare beneficiaries.
AB  - This study used a focus group methodology to examine how Medicare beneficiaries
      reacted to messages on specific kinds of preventive action, including those
      adopted by public and private section health organizations. Beneficiaries were
      asked to rank the messages on their own, and then to discuss their rankings in
      focus groups. The best-received messages advocated a collaborative patient
      provider relationship. They also specified which actions to take, and how to
      implement them. The authors conclude that public health campaigns to reduce
      errors need not undermine trust in providers.

PMID- 12500365
TI  - Assessing Medicare beneficiaries' readiness to make informed health plan choices.
AB  - The Transtheoretical Model (TTM, the "stage model") can guide development of
      programs to increase Medicare beneficiaries' readiness to make informed health
      plan choices. In this study, TTM staging algorithms were developed to assess
      readiness to engage in three types of informed choice: (1) learning about the
      Medicare program; (2) learning about Medicare health maintenance organizations
      (HMOs); and (3) reviewing different plan options. Stage of change based on all
      three algorithms is related to knowledge about the Medicare program and
      information-seeking. Findings provide evidence for the construct validity of the
      stage measures and for the applicability of the TTM to informed choice among
      beneficiaries.

PMID- 12500366
TI  - Family members and friends who help beneficiaries make health decisions.
AB  - People enrolled in Medicare often turn to family members and friends for help in
      making health decisions, including Medicare health plan choices. To learn how
      family members and friends participate in decisionmaking, what information they
      currently use, and what information they would like, we held eight focus groups
      in San Diego and Baltimore. Although responses were different in the two markets,
      participants in both cities reported receiving inadequate information and
      indicated they were largely unaware of available CMS-supported information.
      Beneficiaries want easy-to-use print materials targeted to their needs and
      opportunities to participate in seminars and receive personal counseling.

PMID- 12500367
TI  - Medicare beneficiary satisfaction with durable medical equipment suppliers.
AB  - CMS has recently launched a series of initiatives to control Medicare spending on
      durable medical equipment (DME) and prosthetics, orthotics, and supplies
      (DMEPOS). An important question is how these initiatives will affect beneficiary
      satisfaction. Using survey data, we analyze Medicare beneficiary satisfaction
      with DMEPOS suppliers in two Florida counties. Our results show that
      beneficiaries are currently highly satisfied with their DMEPOS suppliers.
      Beneficiary satisfaction is positively related to rapid delivery, training,
      dependability, and frequency of service. Results of our analysis can be used as
      baseline estimates in evaluating CMS initiatives to reduce Medicare payments for
      DMEPOS.

PMID- 12500368
TI  - Including hospice in Medicare capitation payments: would it save money?
AB  - Hospice services received by Medicare risk-based health maintenance organization
      (HMO) enrollees are paid on a non-capitated basis, creating financial incentives
      for HMOs to encourage their terminally ill patients to elect hospice. Using
      Medicare administrative records for 1998, we found that hospice enrollment in the
      last month of life was significantly higher among HMO enrollees than among
      beneficiaries in fee-for-service (FFS). However, low mortality rates among HMO
      enrollees produced similar population-based rates of hospice use in the HMO and
      FFS sectors. Simulations showed that including hospice care under capitation
      payments in July 1998 would have produced very small savings for Medicare.

PMID- 12500369
TI  - HEDIS performance trends in Medicare managed care.
AB  - The authors analyzed performance trends between 1996 and 1998 for health plans in
      the Medicare managed care program. Four measures from the Health Employer Data
      and Information Set (HEDIS) were used to track performance changes: adult access
      to preventive/ambulatory health services, beta blocker treatment following heart
      attacks, breast cancer screening, and eye exams for people with diabetes. Using a
      cohort analysis at the health plan level, statistically significant improvements
      in performance rates were observed for all measures. Health plans exhibiting
      relatively poor performance in 1996 accounted for the largest share of overall
      improvement in these measures across years.

PMID- 12500370
TI  - Reconciling medical expenditure estimates from the MEPS and the NHA, 1996.
AB  - This article compares 1996 estimates of national medical care expenditures from
      the Medical Expenditure Panel Survey (MEPS) and the National Health Accounts
      (NHA). The MEPS estimate for total expenditures in 1996 was $548 billion;
      whereas, the NHA estimate for personal health care (PHC) in 1996 was $912
      billion. Much of this apparent difference, however, arises from differences in
      scope between MEPS and NHA--rather than from differences in estimates for
      comparably-defined expenditures. We adjusted the NHA for differences in included
      populations and types of services covered, finding a much smaller difference
      between MEPS and a comparably-defined NHA.

PMID- 12500371
TI  - States given greater flexibility in Children's Health Insurance Program.

PMID- 12500373
TI  - Medicare-endorsed drug discount card program announced.

PMID- 12500372
TI  - Diet and exercise dramatically delay type 2 diabetes.

PMID- 12500374
TI  - Critical appraisal of economic analysis studies.

PMID- 12500375
TI  - Molecular imaging: the next frontier.

PMID- 12500376
TI  - Spiral computed tomography for acute pulmonary embolism.
AB  - Imaging algorithms utilizing V/Q scanning, leg ultrasound and pulmonary
      angiography have substantial limitations, and may result in patients being
      treated on clinical grounds without a definitive diagnosis. Hence, the
      introduction of spiral CT angiography of the pulmonary arteries has been greeted
      with enthusiasm.

PMID- 12500377
TI  - Primary epiploic appendagitis: 4 case reports.

PMID- 12500378
TI  - Radiofrequency ablation of malignant hepatic neoplasms.
AB  - OBJECTIVE: To assess the safety and efficacy of radiofrequency ablation (RFA) in
      the treatment of malignant neoplasms of the liver. METHODS: Sixty-seven patients
      received RFA for primary or secondary hepatic malignancies. Patients were
      followed prospectively with computed tomography (CT) scanning to assess for
      therapeutic response, disease progression and complications. RESULTS: Eighty
      eight lesions were treated, including 57 hepatocellular carcinomas, 28
      metastases, 2 cholangiocarcinomas and 1 hepatic plasmacytoma. Mean tumour size
      was 2.7 cm (range 0.5-6.9 cm). A total of 101 ablations were performed (66
      percutaneously, 35 intraoperatively). Over a mean follow-up period of 142 days,
      results were available for 85 lesions. Local tumour control was achieved for 61
      (72%) lesions, but new distant lesions developed in 6 of these cases. Residual
      disease was present in 20 (23%) lesions, and 4 (5%) lesions developed local
      recurrence. There were 10 complications, including 1 death in a patient who
      developed a liver abscess and subsequently died from hepatic failure.
      CONCLUSIONS: RFA is safe and effective in the treatment of hepatic malignancies.
      Local tumour control can be achieved in most cases; however, careful surveillance
      is important for detecting recurrent disease, as well as new lesions distant from
      the treated site.

PMID- 12500379
TI  - Computed tomographic diagnosis of unsuspected pyelonephritis in children.
AB  - OBJECTIVE: To emphasize the utility of computed tomography (CT) in the diagnosis
      of pyelonephritis in children with complex comorbidities. METHODS: We
      retrospectively reviewed the CT imaging studies and medical records of 12
      patients (8 girls, 4 boys; aged 2-18 years [mean 8.6 yr]) who did not have a
      classic presentation of pyelonephritis but were diagnosed by CT. All patients had
      fever at clinical presentation, and pyelonephritis was not suspected in any case.
      Two children had negative urine cultures before imaging. RESULTS: All 12 patients
      had wedge-shaped areas of hypoattenuation on CT, 7 bilaterally; 10 had
      enlargement of an involved kidney; 5 had perinephric fat stranding; and 3 had
      focal abscesses. CONCLUSIONS: Although classic and uncomplicated pyelonephritis
      is a clinical diagnosis that does not require imaging, sometimes the presentation
      may be equivocal and the diagnosis unsuspected. Pyelonephritis is one of several
      potential sources of fever that can be simultaneously evaluated using CT. Using.
      CT, the unsuspected diagnosis of pyelonephritis can be made and therapy initiated
      before the urine culture is positive.

PMID- 12500380
TI  - The cost of angiography procedures: OHIP gets a bargain.
AB  - OBJECTIVE: To determine the costs for 1000 randomized interventional angiographic
      procedures. METHODS: An 9-page paper form was used to manually record the
      consumables, technologist time, room occupancy time and recovery room time for 80
      different procedures collected over a 2-year period. The average cost for
      expendables per procedure was calculated for procedures that occurred 5 or more
      times. RESULTS: Of the 1000 procedures surveyed, there were 20 that had 10 or
      more occurrences, 9 that occurred 5-9 times and 51 that occurred less than 5
      times, of which 32 had only a single occurrence. The total expendables used were
      $514,008. The total examination time was 1158 hours. The total technologist time
      was 2493 hours, and the total recovery room time was 1806 hours. Examples of the
      average cost per procedure are: cerebral angiogram (n = 249), avg. cost $441.24,
      and transvenous liver biopsy (n = 30), avg. cost $642.89. The coefficient of
      variation for procedure costs ranged from 15% to 139%. There were no correlations
      of technician time or procedure technical cost with the date of scan, indicating
      that there was no systematic increase or decrease in costs over the survey
      period. There were moderate correlations of the technical cost of a procedure
      with technologist time (Pearson r = 0.69) and the duration of a procedure
      (Pearson r = 0.73). The technical costs of interventional procedures were
      significantly underfunded; the reimbursement from the Ontario Hospital Insurance
      Plan was $278,446, or 54% of the actual costs. Fourteen procedures were
      reimbursed at below 50% of their costs. CONCLUSION: This shortfall in funding has
      serious consequences for the types and numbers of procedures that are possible in
      radiology departments. Funds must be diverted from other places to prevent
      serious rationing of these services.

PMID- 12500381
TI  - Multilevel vertebroplasty via a single pedicular approach using a curved 13-gauge
      needle: technical note.

PMID- 12500382
TI  - Coexistence of primary bone tumours: report of 4 cases of collision tumours.
AB  - OBJECTIVE: To report, in 4 patients, the occurrence of 2 different primary
      tumours in proximity in the same bone. Three patients had osteosarcomas, and 1
      had a giant cell tumour; all had coincident metaphyseal fibrous defect. METHODS:
      Four patients (2 women, 1 man and 1 boy; 18, 25, 24 and 10 years of age,
      respectively) presented with progressive pain in the knee and distal thigh. All
      were studied by radiography, magnetic resonance imaging was done in 3 patients,
      and diagnostic open biopsy was performed for all. RESULTS: Radiologic studies
      demonstrated tumours in the distal end of the femur in all 4 patients. Biopsy
      tissue showed a metaphyseal fibrous defect in all, with coexistence of an
      associated giant cell tumour in 1 patient and an osteosarcoma in each of the
      others. In all cases, the metaphyseal fibrous defect was penetrated by the
      adjacent tumour. CONCLUSIONS: Despite the relative prevalence of metaphyseal
      fibrous defect, giant cell tumour and osteosarcomas in the distal end of the
      femur and their occurrence in approximately the same age group, their association
      has rarely been reported. As both giant cell tumours and osteosarcomas are
      usually diagnosed late in their clinical course, they may outgrow and destroy any
      evidence of pre-existing metaphyseal fibrous defect. The rate of destruction is
      also influenced by the distance between the 2 lesions--the shorter the distance,
      the earlier the destruction.

PMID- 12500383
TI  - Mixed gangliocytoma--adenoma of the sella: case report.

PMID- 12500384
TI  - Excitotoxicity and the future of stroke imaging.

PMID- 12500385
TI  - IVP or CT for suspected urolithiasis: reply.

PMID- 12500386
TI  - Residents' corner. Answer to case of the month #86. Emphysematous gastritis.

PMID- 12500387
TI  - Residents' corner. Answer to case of the month #87: Pulmonary mucormycosis with
      angioinvasion of the left subclavian artery.

PMID- 12500388
TI  - [Molecular genetic progression on nasopharyngeal carcinoma].
AB  - The aim of this paper was to discuss the molecular genetic events in the
      development and progression of nasopharyngeal carcinoma (NPC), and the
      correlation between genetic alterations and clinicopathological changes of NPC.
      Analyzed by LOH (loss of heterozygosity) and CGH (comparative genomic
      hybridization) in primary NPC, high frequent allelic losses were observed on
      chromosomes 1p, 3p, 9p, 9q, 11q, 13q, 14q, 16q, and 19q, and the minimum deletion
      regions were also localized; there are closely association between LOH on certain
      deletion regions in NPC and the clinicopathological parameters. In the group of
      NPC with higher LOH value (FAL), together with higher antibody titers of EBV
      IgA/VCA and IgA/EA, most of the NPC showed more invasive of primary T stage (T3 +
      T4), TNM (III + IV stage) and far lymph node metastasis. High frequent
      chromosomal gain regions were observed on chromosomes 1q, 2q, 3q, 6p, 6q, 7q11.2,
      8q, 11q13, 12, 15q, 17q, and 20q, indicating that there may exist oncogenes which
      are activated on the gain regions in NPC. CGH analysis showed that gains on
      chromosome 1q, 8q, 18q, and loss on 9p were closely related to advanced stage of
      NPC. LOH study also showed high frequent LOH on 3p in normal nasopharyngeal
      epithelium (74%) and dysplasia lesions (75%) from the Southern Chinese,
      suggesting that LOH at 3p may be an earlier genetic event of NPC tumorigenesis.
      Linkage analysis indicate that the HLA gene and cytochrome p4502E gene may be
      susceptibility genes of NPC. New potential susceptibility gene locus has also
      been localized by this study. cDNA microarray demonstrated differential
      expression of cell cycle proteins, anti-apoptotic factors, oncogenes/tumor
      suppressors, growth-enhancing factors of EGR1, tumor-derived growth factor 1,
      platelet-derived growth factor A chain; differential expression were also
      observed in different clinical stage NPC. Genetic instabilities (losses and
      gains) are common molecular events in NPC, and play very important role in the
      development and progression of NPC. Through LOH, CGH, linkage, and cDNA
      microarray study, we can find specific biomarkers of NPC, and will support us
      biomarkers which can be used for earlier diagnosis and prognosis of NPC. More
      importantly, these biomarkers may be useful in the development of a NPC molecular
      staging system, which could augment current clinicopathological classification
      and staging systems.

PMID- 12500389
TI  - [Analysis of proteins with altered expression in human esophageal squamous cell
      carcinomas].
AB  - BACKGROUND & OBJECTIVE: Esophageal squamous cell carcinoma is characterized by
      high incidence and high mortality. This study was designed to identify the
      proteins dysregulated in ECSS by. METHODS: Microdissection of routinely unstained
      frozen sections was used to procure cancer cells from seven esophageal squamous
      cell carcinomas, and esophageal epithelial cells from normal tissues adjacent to
      the tumors. By two-dimensional electrophoresis, protein profiles of normal and
      cancerous tissues were obtained. Selected proteins with altered expression in
      tumors were identified through MALDI-TOF-MS. RESULTS: Compared the protein
      profiles of tumors with those of normal epithelia, 11 proteins were found as
      dysregulated in tumors. Among them, HSP27 was observed up-expressed and three
      isoforms of ANNEXIN I were seen down-expressed in cancerous tissues. CONCLUSION:
      Two-dimensional electrophoresis coupled with mass spectrometry can contribute to
      rapidly screen dysregulated proteins in human maligancies. Altered expressions of
      HSP27 and ANNEXIN I were the frequent events in Chinese esophageal squamous cell
      carcinomas.

PMID- 12500390
TI  - [Inhibiting target gene expression and controlling growth of Epstein-Barr virus
      transformed cells by antisense RNA transcripts].
AB  - BACKGROUND & OBJECTIVES: The latent membrane protein gene (LMP) of Epstein-Barr
      virus (EBV) was thought to play an important role in the carcinogenesis of
      nasopharyngeal carcinoma (NPC). In this study, the authors investigated the
      effects of antisense RNA (AsRNA) on LMP for down regulating at the target gene
      over expression in EBV transformed lymphoid cells, and set up an antisense system
      to inhibit LMP expression. METHODS: Constructing the single strand antisense
      transcription system in vitro, the authors have got large amount of AsRNA.
      Designing and setting up an antisense tracing system in situ (ATSIS), the authors
      could observe the living particles of AsRNA/sense RNA duplex dimer. With time
      lapse phase-contrast microscopy, the agglutination phenotype on living cells was
      easily detected by MTT test, the inhibition rate on EBV transformed cells was
      calculated. RESULTS: LMP 1.9 fragment ligated into pGEM vector in reverse
      orientation have been constructed and produced a plentiful amount of AsLMPmRNA
      which could incorporated into both B95-8 and C1936 cell lines by endophagocytosis
      and formed the duplex dimer of As/Sense RNA. This particles have been visualized
      in situ when labelling 35S isotope by ATSIS. When AsLMPmRNA acted as agents for
      specific inhibition to LMP over expression, the transform phenotype of cell
      agglutination have been suppressed and MTT particle formatin was apparently
      reduced both two EBV tansformed cell lines. CONCLUSION: AsLMPmRNA targets at
      sense strand have a high effectiveness of down-regulation on EBV-LMP
      overexpression. This down regulating function of LMP and growth inhibition on
      transformed cell is demonstrated by the antisenes tracing system in situ (ATSIS).
      The results provide a clue to overcome the latent EBV infection in human bodies
      all living long time and to prevent it inducing NPC in high incidence area by
      antisense strategies.

PMID- 12500391
TI  - [Analysis of gene expression patterns of periphery lymphocytes in patients with
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: The periphery T and B lymphocytes are most important
      immune cells in a body. Analysis for the gene expression profiles of the immune
      cells will contribute to the understanding of the biological essence of immune
      suppression. The advanced technique of DNA microarray make it possible to monitor
      the expression of thousands of genes simultaneously in one hybridization
      experiment until recently. In this paper, the authors investigated the genes
      differentially expression in periphery lymphocytes between the patients with
      Nasopharyngeal Carcinoma(NPC) and health donors to explore the features of gene
      expression in immune cells of NPC patients. METHODS: The BioDoor10s/D chips
      containing 2000 spots of cDNAs were used to investigate the difference of the
      expression. Both the mRNAs from periphery lymphocytes of NPC patients (2 x 10(8))
      and health donors(2 x 10(8)) were reversely transcribed to cDNA with the
      incorporation of fluorescent(cy5 and cy3) labeled dUTP to prepare the
      hybridization probes. After hybridization, BioDoor10s/D chips were scanned for
      the fluorescent intensity. The differentially expressed genes were screened.
      RESULTS: The total of 62 genes has differentially expression in NPC periphery
      lymphocytes. The number of over- and lower-expressed genes were 5 and 57,
      respectively. There were 3 genes coding for signal transductive proteins in 5
      over-expressed genes. Five genes coding for signal transductive proteins were
      involved in 9 genes with lowest-expression (cy5/cy3 > or = 0.3). CONCLUSION:
      There was the consistent tendency toward lower-expressed gene in periphery
      lymphocytes from the patients with NPC. The disorder in signal transductive
      function of lymphocytes may be a factor distinguishing NPC immunity from the
      health one. Improvement of gene expressing profil may also be a way to enhance
      immune function in tumor patients.

PMID- 12500392
TI  - [Matrix metalloproteinase-2 and angiogenesis in gastric cancer].
AB  - BACKGROUND & OBJECTIVE: The proliferation and metastasis of solid tumor depend on
      angiogenesis. Experiment study showed that matrix metalloproteinase-2(MMP-2) may
      play an important role in angiogenesis of solid tumor. The current study was
      designed to explore the role and the significance of MMP-2 on angiogenesis in
      gastric cancer through observing the relationship between the expression of MMP-2
      and microvessel density (MVD) in gastric cancer tissues, paracancerous tissues,
      and incisal margin normal tissues. METHODS: A total of 50 specimens resected was
      investigated by S-P immunohistochemical staining with a anti-MMP-2 monoclonal
      antibody and a monoclonal antibody against F VIII RAg. The expression of MMP-2
      and MVD in various regions of the gastric cancer tissues, paracancerous tissues
      and incisal margin normal tissues were detected and the relationship between the
      expression of MMP-2 and MVD, as well as their relationship with clinicopathologic
      factors were analyzed. RESULTS: The expression of MMP-2 negative or low in normal
      tissues. The high expression of MMP-2 in cancer tissues was significantly higher
      than in the paracancerous tissues (64.0% vs 28.0%, chi 2 = 7.48, P < 0.01). The
      low expression of MMP-2 in paracancerous tissues was significantly higher than in
      the normal tissues (52.0% vs 26.0%, chi 2 = 6.18, P < 0.05). The MVD in the cases
      with the high expression of MMP-2 was significantly higher than in those with the
      low expression of MMP-2 in cancer tissues and paracancerous tissues (30.71 +/-
      7.41 vs 26.15 +/- 4.82, t = 2.11, P < 0.05; 15.31 +/- 5.23 vs 9.61 +/- 2.17, t =
      3.98, P < 0.01). Moreover, the high expression of MMP-2 (81% vs 51.7%, chi 2 =
      4.67, P < 0.05; 87.0% vs 44.4%, chi 2 = 9.47, P < 0.01; 81.8% vs 50.0%, chi 2 =
      5.41, P < 0.05; 89.5% vs 48.4%, chi 2 = 8.63, P < 0.01) and its MVD (28.89 +/-
      5.37 vs 25.21 +/- 5.37, t = 2.39, P < 0.05; 27.84 +/- 2.32 vs 25.12 +/- 3.45, t =
      2.02, P < 0.05; 28.63 +/- 3.12 vs 25.53 +/- 4.23, t = 2.87, P < 0.01; 28.84 +/-
      2.64 vs 25.31 +/- 4.35, t = 3.09, P < 0.01) in cancer tissues were significantly
      related with the serosal invasion, grade of differentiation, lymph node, and
      liver metastasis(P < 0.05-0.01). CONCLUSIONS: The high expression of MMP-2 was
      significantly associated with MVD, biological behaviors of gastric cancer
      tissues, MMP-2 might be one of the important factors in the angiogenesis of
      gastric cancer.

PMID- 12500393
TI  - [Expression of GST-pi and HBV infection in hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: The expression of glutathione S-transferases(GST-pi)
      might abnormally increase in many carcinogenesis, and the alteration of GST-pi
      preceded than that alteration of cell morphology. This study was designed to
      investigate the expression of glutathione S-transferases (GST-pi) and its
      relationship with hepatitis B virus (HBV) infection in hepatocellular carcinoma
      (HCC). METHODS: Hepatitis B surface antigen (HBsAg), Hepatitis B core antigen
      (HBcAg), and GST-pi were detected by immunohistochemical staining and HBV DNA was
      detected by in situ hybridization (ISH) in total 86 samples of chronic hepatitis,
      liver cirrhosis, paratumor cirrhosis, HCC, and normal liver tissue. RESULTS: The
      positive expression rates of HBsAg, HBcAg, and HBV DNA were 61.9% (13/21), 42.9%
      (9/21), and 75.0% (12/16) in chronic hepatitis; 64.0% (16/25), 36.0% (9/25), and
      83.3% (15/18) in liver cirrhosis; 72.7% (16/22), 61.1% (11/18), and 85.7% (12/14)
      in the paratumor cirrhosis, as well as 45.0% (14/31), 50.0% (14/28) and 64.3%
      (9/14) in HCC. HBV DNA positive granules in chronic hepatitis, liver cirrhosis,
      and the paratumor cirrhosis were more and stronger than that in HCC,
      respectively. The positive expression rates of GST-pi were 25.0% (4/16), 17.6%
      (3/17), 53.3% (8/15), and 60.0% (9/15) in chronic hepatitis, liver cirrhosis, the
      Paratumor cirrhosis, and HCC, respectively. The positive rate of GST-pi in the
      paratumor cirrhosis was significantly higher than that in the liver cirrhosis
      without tumor (P < 0.05), but the same as in HCC (P > 0.05). CONCLUSIONS: Most of
      the HCC cases were closely associated with chronic hepatitis and liver cirrhosis
      of HBV infection. The HBV infection may increase expression of GST-pi. The
      paratumor cirrhosis may be a sequential lesion of precancerous cirrhosis around
      HCC.

PMID- 12500394
TI  - [Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].
AB  - BACKGROUND & OBJECTIVES: Ras gene plays an important role in the extra- and intra
      cellular signal transduction pathway. It mediates series cascade reactions, and
      eventually actives transcriptional factors in nucleus. It is unknown on the
      mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras
      mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis
      of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell
      line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant
      type [12Asp] K-ras4B gene. METHODS: (1) Full-length [12Asp]K-ras4B cDNA was
      amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2)
      Morphological change, growth kinetics in vitro and tumorigencity in nude mice in
      vivo after-before transfection were observed. (3) To test the cell growth
      kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation
      method. RESULTS: (1) The authors have successfully constructed eukaryotic
      expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B
      mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro
      and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into
      pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly
      in comparison with control group. (4) These findings indicate the expression of
      RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K
      ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B
      cell growth (P < 0.05). CONCLUSIONS: (1) [12Asp]K-ras4B gene alone is able to
      cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2)
      [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf
      signaling pathway.

PMID- 12500395
TI  - [Experimental study of anti-VEGF hairpin ribozyme gene inhibiting expression of
      VEGF and proliferation of ovarian cancer cells].
AB  - BACKGROUND & OBJECTIVE: Growth of solid tumor metastases are critically dependent
      on angiogenesis. Vascular endothelial growth factor (VEGF), also known as
      vascular permeability factor, has been identified as one of the most potent
      inducers of tumor associated angiogenesis, studies have shown that VEGF plays an
      important role in angiogenesis which is associated with epithelial ovarian
      cancer. Until now, many strategies for gene therapy have been developed. Among
      them is Ribozyme-based therapeutics for cancer which might be devised to inhibit
      tumor growth or prevent metastases. Angiogenesis is required for sustained tumor
      growth, making the VEGF pathway another promising target for either small
      molecule or nucleic acid-based therapeutics. Little is known about the role of
      VEGF in ovarian tumorigenecity. We propose to block the autocrine and/or
      paracrine pathway of VEGF in ovarian cancer using anti-VEGF hairpin ribozyme gene
      to see whether the growth of tumor cells could be inhibited and to further
      exploit its mechanisms. METHODS: Anti-VEGF hairpin ribozyme gene eukaryotic
      expression vector was introduced into ovarian cancer SKOV3 cells by lipofectin
      mediation and positive clones were screened by G418; Ribozyme expression was
      confirmed by RNA dot blot; The VEGF expression of SKOV3 cells before or after
      transfection were detected by immunohistochemical and immunofluorescence and flow
      cytometer immunofluorescence methods, MTT, colony forming, soft agar colony
      forming, and FCM were used to observe the effect of proliferation to ovarian
      cancer cells. RESULTS: VEGF expression decreased distinctly in SKOV3-RZ cells.
      The growth of transfected SKOV3-RZ cells were slower, The average colony forming
      efficiency and soft agar colony forming efficiency of SKOV3-RZ cells(12.7 +/- 1.4
      and 9.4 +/- 2.0, respectively) decreased distinctly (P < 0.001). The SKOV3-RZ
      cells of G1 stage increased(P < 0.01), the SKOV3-RZ cells of S stage were
      reduced(P < 0.01). CONCLUSIONS: Anti-VEGF hairpin ribozyme gene can inhibit the
      proliferation of ovarian cancer SKOV3 cells. This provides a experimental basis
      for cure human ovarian cancer with antiangiogenesis method.

PMID- 12500396
TI  - [Detection of cell apoptosis induced with anti-Fas antibody in bladder carcinoma
      cell line by single cell gel electrophoresis].
AB  - BACKGROUND & OBJECTIVE: Fas, a death factor, can induce apoptotic death of cells.
      Many malignant tumor cells expressed Fas can not develop apoptotic death, this
      may be because of low Fas expression. Therefore we investigate the relationship
      between expression level of Fas and anti-Fas biological responsiveness. METHODS:
      With direct immunofluorescence flow cytometry, the expression of Fas was detected
      in bladder carcinoma cell line EJ, TNF alpha treated EJ, and Fas gene transfected
      EJ. The three kinds of EJ cells died by apoptosis were induced with anti-Fas
      antibody DX2 IgG1K and determined by SCGE and flow cytometry (FCM). RESULTS:
      Expression of Fas in bladder carcinoma cell line EJ, TNF alpha treated EJ, and
      Fas gene transfected EJ was 19.18%, 28.03%, and 68.69%, respectively. Cellular
      apoptosis induced with anti-Fas antibody DX2 IgG1K in bladder carcinoma cell line
      EJ was least, in TNF alpha treated EJ moderate, and in Fas gene transfected EJ
      the most. CONCLUSIONS: Fas gene transfection is an effective method to increase
      Fas expression; the sensitivity of EJ cell line to Fas-mediated apoptosis is
      mainly dependent upon the expression of Fas.

PMID- 12500397
TI  - [Inhibition of growth and metastases of human colon cancer xenograft in nude mice
      by angiogenesis inhibitor endostatin].
AB  - BACKGROUND & OBJECTIVE: Tumor angiogenesis is essential for growth and metastases
      of colon cancer. Angiogenesis inhibitors can induce apoptosis in colon cancer by
      inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor
      growth and metastases of human colon cancer. Anti-angiogenic cancer therapy is
      important for selecting the timing and method of operation and program of complex
      treatment and enhancing the five-year survival rate of patients with colon
      cancer. In this study, we aimed to investigate the effects of angiogenesis
      inhibitor endostatin on the growth and metastases of colon cancer in vivo.
      METHODS: Metastatic model simulating human colon cancer was established by
      orthotopic implantation of histologically intact human tumor tissue into colon
      wall of nude mice. Endostatin was administered s.c. at dose of 0 mg/kg, 5 mg/kg,
      10 mg/kg and 20 mg/kg, every day for six weeks. Seven weeks after implantation,
      the tumor weight and inhibition rates and intratumoral microvessel density (MVD)
      and apoptotic index (AI) and the presence of metastases are evaluated
      respectively after the mice were sacrificed. RESULTS: In compared with the
      untreated controls, growth of the orthotopically implanted tumor was
      significantly reduced in weight in mice treated with endostatin with an
      inhibition rate of 0%, 67.9%, 84.0%, and 90.1% at the dosage of 0 mg/kg, 5 mg/kg,
      10 mg/kg, and 20 mg/kg, respectively. The MVD also decreased significantly in the
      treated mice [(12.8 +/- 4.1) versus (5.9 +/- 2.5), (2.2 +/- 1.4) and (0.74 +/-
      0.3)]. The AI increased significantly in the treated mice [(3.87 +/- 2.61)%,
      versus (6.89 +/- 5.18%), (13.24 +/- 4.76)% and (20.97 +/- 9.04)%]. The incidences
      of peritoneal metastases were also significantly inhibited in the treated mice
      (90.0% versus 36.4%, 25.0%, and 0%). The incidences of liver metastases were also
      significantly inhibited in the treated mice (80.0% versus 27.3%, 16.7% and 0%).
      Tumor metastases to the liver and peritoneaum were also significantly inhibited
      in a dose-dependent manner (P < 0.05). CONCLUSIONS: Angiogenesis inhibitor
      endostatin can induce apoptosis in colon cancer by inhibiting tumor angiogenesis
      and has strong inhibitory effect both on tumor growth and metastases of human
      colon cancer xenograft in nude mice.

PMID- 12500398
TI  - [Relationship between expression of p27 and DNA ploidy in colorectal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Cell cycle regulation changes in most of tumors. We can
      regard tumors as a kind of cell cycle diseases. p27 protein is a main negative
      cell cycle regulator, meantime it is an important prognosis factor of tumors. The
      significance of reduced expression and altered sbucelluar localization of p27
      protein is unclear in progression of colorectal carcinoma. The relevance of p27
      protein and DNA ploidy hasn't been reported in colorectal carcinoma. The study
      was designed to investigate the relationship between the expression of p27
      protein and clinicopathological features, DNA ploidy in colorectal carcinoma.
      METHOD: The expression of p27 was observed in 40 colorectal cancer cases using
      immunohistochemical technique, and DNA content of cancer cells was analyzed using
      DNA imaging analysis system. RESULTS: The high p27 expression rate was 62.5%
      (25/40), while low expression rate was 37.5% (15/40). Low p27 expression was
      significantly associated with low tumor grade. (P < 0.05). In addition to nuclear
      staining, 32.5% (13/40) of the carcinoma displayed p27-positive immunoreactivity
      in cytoplasm. Cytoplasmic localization of p27 was association with late Dukes
      stage(P < 0.01) and high incidence of lymph node metastases(P < 0.05). The
      detective rate of polyploidy cell in the patients with p27 lower expression (22.2
      +/- 11.3%) was significantly higher than that with p27 higher expression (8.0 +/-
      7.7%, P < 0.001). CONCLUSION: Reduced expression and altered subcellular
      localization of p27 play a role in progression of colorectal carcinoma; one
      suppression tumor mechanism of p27 might be to prevent the acquisition of
      polyploid DNA content in colorectal carcinoma cells.

PMID- 12500399
TI  - [Significance of ALK gene expression in neoplasms and normal tissues].
AB  - OBJECTIVE: This study was designed to investigate the clinicopathologic
      significance of the ALK gene expression in neoplasms and normal tissues. METHODS:
      Using the immunohistochemical method, the expressions of ALK gene were examined
      on 14 anaplastic large cell lymphoma (ALCL). 10 Hodgkin's lymphoma, 46 B
      lymphoma, 13 T lymphoma, 21 malignant astrocytoma, 5 medulloblastoma, 5
      ependymoma, 69 carcinomas, 19 sarcomas, and many normal tissues. RESULTS: (1) The
      expression rate of ALK was 64.3% in ALCL, it is significantly higher than that in
      Hodgkin's lymphoma, B lymphoma, and other T lymphoma(P < 0.01). (2) There was
      strongly expression of ALK in hepatocellular carcinoma, malignant astrocytoma,
      and medulloblastoma. (3) There was weakly expression of ALK in placenta tissue
      and astrocyte. CONCLUSIONS: (1) The ALK protein is a very important molecular
      marker in ALCL, it is very helpful for diagnosing and distinquishing ALCL. (2)
      ALK gene may take part in the origin and development of hepatocellular carcinoma,
      malignant astrocytoma, and medulloblastoma and may be an important gene
      associated with neoplasms.

PMID- 12500400
TI  - [Relationship between expression of c-myc and p53 in liposarcoma].
AB  - BACKGROUND & OBJECTIVE: The relationship between liposarcoma and gene c-myc and
      p53 is not clear. There are also different reports on p53 mutation in
      liposarcoma. This study was designed to investigate the relationship between the
      expression of c-myc and p53 genes and liopsarcomas. We hope to better understand
      the role of the c-myc and p53 genes in molecular biology. METHODS:
      Immunohistochemical labelled streptavidin-biotin (LSAB) method, single strand
      conformation polymorphism analysis of polymerase chain reaction products (PCR
      SSCP), and DNA sequencing were used. RESULTS: 38.09% (16/42) liposarcoma samples
      detected were immunohistochemically c-myc protein positive. p53 protein was
      detected in 52 liposarcomas with the positive staining rate of 48.08% (25/52). In
      different subtypes of liposarcomas, the positive staining rates of c-myc and p53
      gene proteins were much lower in well-differentiated liposarcomas than in the
      poorly differentiated liposarcomas. There was a positive correlation between c
      myc and p53 expression in liposarcoma. There was no statistical significance for
      the different positive staining rate of c-myc and p53 protein in the primary and
      the recurrent liposarcoma. Abnomality in the single-stranded DNA pattern was
      determined by PCR-SSCP analysis in 2 samples (pleomophic liposarcomas). Missense
      mutation in exon 8 of codon 268 of p53 gene (AAC-->ATC) were detected by DNA
      sequencing. Another heterozygotic cosense mutation may exist at exon 6 of codon
      221 of p53 gene (GAG-->GAA). CONCLUSIONS: The c-myc and p53 protein are
      associated with the development, differentiation, and malignancy of liposarcoma,
      but not with the recurrence of liposarcoma. Detecting the level of c-myc and p53
      protein expression may be valuable in evaluating the level of differentiation and
      malignancy of liposarcoma. c-myc and p53 play synergic roles in the cooperation
      of development of liposarcoma. There appear the point mutation on exon 8, 6 of
      p53 gene.

PMID- 12500401
TI  - [Clinical value of inducing chemotherapy for patients with advanced tongue
      cancer].
AB  - BACKGROUND & OBJECTIVE: It was reported that inductive chemotherapy play an
      important rolc in malignant tumors of head and neck. The aim of this study was to
      evaluate the role of the inductive chemotherapy in the treatment of advanced
      tongue cancer. METHODS: Eighty-three cases with advanced tongue squamous cell
      carcinoma were treated in our hospital from Jun 1989 to Dec 1995, divided two
      groups. Thirty-two cases were treated by surgery alone, and fifty-one cases were
      treated by surgery with preoperation, inducting chemotherapy including twenty
      seven cases treated by bleomycinA5 alone, thirteen cases treated by combination
      chemotherapy(DDP, 5-FU, BLM), and eleven cases treated by lingual artery
      chemoembolization. RESULTS: Three and five-year survival rates in surgery group
      and multidisciplinary management group were 50%, 46.7% and 60.6%, 50%
      respectively. Their recurrence rates were 31.3% and 39.2% respectively.
      CONCLUSIONS: Combined management of advanced tongue cancer could not prolong the
      three and five years survival time, but it could increase loco-regional tumor
      control rate and prolong the disease-free survival and improve the quality of
      life.

PMID- 12500402
TI  - [Expression of CD44v6 before and after chemotherapy in patients with breast
      cancer and its significance].
AB  - BACKGROUND & OBJECTIVE: CD44 is the member of adhered molecular family, and
      related to the formation and metastasis of tumor. Especially the CD44v6 isoform
      of its variation form was closed associated with the invasion and metastases of
      tumors. The current study was designed to investigate the relationship between
      the expression of CD44v6 in the blood, cancer tissues, and lymphnode in the
      patients with breast cancer and chemotherapy. METHODS: The expression of CD44v6
      in breast cancer tissue was examined by immunohistochemistry and that in
      circuling lymphocyte and lymphnode adherense cell by flow cytometry. RESULTS:
      CD44v6 level increased in cancer tissue (t = 4.71, P < 0.05) and the metastatic
      lymphnode (t = 5.11, P < 0.05), did not change in circuling lymphocyte (t = 0.98,
      P > 0.05). CD44v6 expressed in tumor cells was strong positive and positive rate
      was 100%. The expression of CD44v6 in benign tumor tissue was negative. After
      chemotherapy with CMF, CD44v6 expressed in tumor cells was still 100%. CD44v6
      level decreased significantly in lymphocyte of cancer tissue (t = 4.13, P <
      0.05), did not change in blood and lymphnode comparing to before chemotherapy.
      CONCLUSIONS: It was proved that the expression of CD44v6 was closely related to
      the metastases of lymphnode and more closely related to the prognosis of breast
      cancer.

PMID- 12500403
TI  - [Tumor angiogenesis in node-negative breast carcinoma].
AB  - BACKGROUND & OBJECTIVE: This study was designed to investigate the vascular
      endothelial growth factor (VEGF) and the microvessel density(MVD) in node
      negative breast carcinoma, and to discuss the relationship of MVD and VEGF to the
      tumor size, histologic grade, and relapse and metastasis. Meanwhile, the
      prognostic value of MVD and VEGF was estimated. METHODS: MVD and VEGF were
      evaluated after immunohistochemical staining using antibody of vascular
      endothelium for factor VIII antigen and VEGF in 62 patients with node-negative
      breast carcinoma respectively. The patients were followed up. RESULTS: VEGF and
      MVD were all associated with histological grade and relapse (P < 0.05), but no
      association with ER and tumorsize; the relapse-free survivals (RFS) and overall
      survivals of patients with high MVD or high VEGF expression were significantly
      lower than that of the patients with low MVD or low VEGF expression (P < 0.01).
      Moreover, the difference of survivals in the patients with high MVD and high VEGF
      expression were more obvious(P < 0.005). Meanwhile, there was association between
      MVD and VEGF (P < 0.01). CONCLUSIONS: The node-negative patients with high VEGF
      expression or high MVD would have poor prognosis. VEGF and MVD could be
      significant prognostic indicators for the patients with node-negative breast
      carcinoma. It has better prognostic value to connected VEGF and MVD. VEGF was an
      important factor in tumor angiogenesis.

PMID- 12500404
TI  - [Clinical analysis of 57 patients with ovarian dysgerminoma].
AB  - BACKGROUND & OBJECTIVE: Ovarian dysgerminoma is an uncommen ovarian malignancy.
      Its clinical features are special and there are many factors influencing the
      prognosis. If treated properly, the patient can be cured. Otherwise it may
      endanger the patient's life. The aim of this study is to investigate the clinical
      features and factors related to prognosis of ovarian dysgerminoma. METHOD: The
      data of 57 patients with pure Ovarian Dysgerminoma were analyzed retrospectively,
      who were admitted to Cancer Center, Sun Yat-sen University of Medical Sciences
      from January 1, 1964 to December 31, 2000. RESULTS: The main clinical features
      were abdominal mass (56.1%), abdominal pain (21.1%), abdominal swelling(17.5%),
      vaginal bleeding(5.3%), genital tract abnormality (5.3%). Twenty-six patients had
      stage Idiseases, 8 stage II, 9 stage III, 1 stage IV and 13 recurrent and
      persistent diseases. The uterus was involved in 41.2% patients with stage II-III
      diseases. Combined modality was given to 52 cases and single-method treatment 5
      cases. The overall 5-year and 10-year survival rate for stage I-IV was 80.1% and
      70.0% respectively. The 5-year survival rate for stage I was 100%, stage II
      55.2%, stage III 55.6%, stage IV 0% and recurrent and persistent diseases 72.7%.
      In the group of stage I, 12 patients received adnexectomy and 14 patients
      underwent hysterectomy and adnex removal, there was no significant difference
      between the 5-year and 10-year survival rate (all 100%) (P < 0.05). Of 23
      patients in stage I group to whom only chemotherapy were given after operation,
      19 cases received 3 or more courses and were well being without recurrence; four
      patients received only one course and one of them recurred 21 months after
      operation. In the group of stage II and III cases the 5-year survival rate was
      86.7% for those whose chemotherapy courses were > or = 4 and 25.0% for patients
      who received less than 4 courses of chemotherapy (P < 0.05). CONCLUSIONS: The
      prognosis of ovarian dysgerminoma is closely related to disease stage and
      modality of treatment. Fertility-preserving operation can be considered in early
      staged patients, and be careful of doing so in middle-late staged cases. Good
      results can be achieved with operation-based combined modality in recurrent
      patients.

PMID- 12500405
TI  - [Primary adenocarcinoma of vagina--attaching 24 cases clinical analysis].
AB  - BACKGROUND & OBJECTIVES: The incidence of primary vaginal adenocarcinoma was
      lower and its treatment was difficult and its prognosis was worse. This study was
      designed to explore the clinical characters, treatment, prognosis of primary
      vaginal adenocarcinoma in this paper as the incidence of primary vaginal
      adenocarcinoma was lower, its treatment was difficult and its prognosis was
      worse. METHODS: From 1964 to 1999, twenty-four patients were reviewed
      retrospectively in our hospital. RESULTS: The main clinical symptoms were vaginal
      bleeding and discharge. The median age was 49 years old. Five patients were
      classified as stage I, 10 patients were stage II, 5 patients were stage III, and
      4 patients were stage IV. The lesion was located in the anterior wall in 8(33.3%)
      patients, the posterior wall in 5(20.8%) patients, the left wall in 1 patient and
      the multiple walls in 10(41.7%) patients. Twenty-four patients were generally
      received radiotherapy, including external-beam and intracavitary irradiation. Two
      patients were concurrently received chemotherapy and irradiation, Eight patients
      were received chemotherapy as the tumor was not control and recurrent or
      metastatic. The survival rate of 3 years was 47.3% and that of 5 years was 34.2%.
      The survival mean time of patients with stage I and stage II was 60.3 months
      obviously much longer than 14.8 months of patients with stage III and stage IV,
      and they were significantly statistical difference (P < 0.01). But the survival
      mean time of patients more than 40 years and less than or equal to 40 years was
      not significantly statistical difference. Eight patients had local recurrence,
      which is the main reason of failure treatment. CONCLUSIONS: Primary vaginal
      adenocarcinomas should mainly be adopted combined treatment depending on
      radiotherapy, but the prognosis was worse, the stage was the important factors
      affecting on the prognosis.

PMID- 12500406
TI  - [Immunohistochemical study on telomerase activity in ovarian sex-cord stromal
      tumors].
AB  - BACKGROUND & OBJECTIVE: Telomerase activity has been detected in a broad range of
      human cancers including epithelial malignancies from in female genital tract, but
      the expression of the telomerase activity in ovarian sex-cord tumors has not been
      reported up to now. In this report we investigated the telomerase activity in
      ovarian sex-cord stromal tumors and its relationship with clinicopathological
      feature. METHODS: Twenty-five cases of ovarian sex-cord stromal tumor, including
      granulosa cell tumors, thecofibromas, sclerosing stromal tumors, and Sertoli
      Leydig cell tumors were retrieved, and the expression of human telomerase reverse
      transcriptase (hTRT) was assessed immunohistochemically using polyclonal antibody
      H231. RESULTS: hTRT were positive in 60.0% of all cases, and the signal mainly
      located in the cytoplasm of tumor cells, especially in luteinized cells and Ledig
      cells. The positive rate was significantly related to different histological
      types and the patients' clinical endocrinal manifestation (P value were 0.01 and
      0.041, respectively), but no statistically significant difference was found
      between the expression of hTRT and tumor histological grade or patients'
      prognosis. CONCLUSIONS: In ovarian sex-cord stromal tumors, the tumor component
      differentiating to luteinized stromal cell has high telomerase activity, and the
      telomerase activity may play an important role in patients' endocrinal disorder.

PMID- 12500407
TI  - [Expression of matrix metaloproteinase and tissue inhibitors in ovarian tumors].
AB  - BACKGROUND & OBJECTIVE: Metalloproteinase(MMPs) is considered to be associated
      with the development of carcinoma, especially with the invasion and metastases of
      cancer. This study was designed to evaluate the relationship between the
      expression of MMP-2, MMP-9, and TIMP-2 and biological behavior of ovarian cancer.
      METHODS: The expression of MMP-2, MMP-9, and TIMP-2 in 128 patients with ovarian
      tumor was determined using immunohistochemical methods, and their relationship to
      many clinicopathological parameters was analyzed. RESULTS: Immunohistochemical
      studies revealed a diffuse granular distribution of MMP-2, MMP-9, and TIMP-2 in
      the cytoplasm of the carcinoma cells. The expression of MMP-2, MMP-9, and TIMP-2
      was stronger in ovarian adenocarcinoma tissue than in ovarian benign tumor tissue
      (P < 0.01). MMP-2 and MMP-9 levels were found to be significantly higher in grade
      III-IV adenocarcinoma than in grade I-II adenocarcinoma (P < 0.01). MMP-2 and MMP
      9 levels were significantly higher in G3 than in G1-2 tumors. Furthermore, the
      expression rate of MMP-2 and MMP-9 was higher in cases with lymph node metastases
      thanin those with non-lymph node metastasis. TIMP-2 expression was contrary to
      the expression of MMP-2 and MMP-9 on that three respects in ovarian carcinomas.
      CONCLUSION: The expression of MMP-2, MMP-9, and TIMP-2 correlate with tumor
      stage, poor differentiation, and lymphonodes metastases, which suggests that co
      expression of MMP-2, MMP-9, and TIMP-2 within the same tumor seem to play an
      important role in the progression of ovarian cancer and could be useful
      prognostic markers for patients with ovarian carcinoma.

PMID- 12500408
TI  - Criteria for standardized nursing languages.

PMID- 12500409
TI  - Don't let the human factors derail "best practices".

PMID- 12500410
TI  - Evaluating process changes in a pediatric hospital medication system.
AB  - This article describes a process change designed to increase the safety of
      prescribing and interpreting complex order sets. All chemotherapy orders written
      for pediatric oncology patients at a major teaching hospital in the Eastern
      United States and the affiliated ambulatory clinic from June 1998 through
      February 2000 (n = 1792) were reviewed to evaluate a new process for
      communication of chemotherapy orders. The multidisciplinary check (MDC) is a
      forum where all disciplines simultaneously review and change complex order sets.
      Evaluation of the MDC included monthly completion rate and classification of
      changes made to orders at MDC. Over the study period, 96% of eligible orders
      received a multidisciplinary check, and 44% were changed. The most common change
      was to clarify discrepancies between the order and the protocol. Changes were
      made to avoid medication errors in 99 of 451 orders. Changes to avoid medication
      errors were more likely to involve nonchemotherapy medications. The MDC is an
      efficient and feasible process to increase safety at the beginning of the
      medication system.

PMID- 12500411
TI  - Clean versus sterile gloves: which to use for postoperative dressing changes?
AB  - Staff nurses have a key role in ensuring that practice is evidenced-based. This
      article discusses the application of a model for evidence-based practice change
      by staff nurses in an acute care setting who examined the practice of using
      sterile gloves for postoperative wound dressing changes. This initiative was in
      response to the challenge that it was unnecessary to use sterile instead of
      nonsterile gloves. Extensive literature search revealed insufficient evidence to
      justify a practice change to nonsterile gloves.

PMID- 12500412
TI  - Outcomes research: making a difference in practice.
AB  - The purpose of this pilot study was to determine whether a significant difference
      in outcome ratings exists from admission to discharge for selected populations.
      Two acute care sites that have standardized nursing languages in their
      computerized clinical documentation systems participated. These data are an
      important start in using patient outcomes to determine the effect of nursing
      interventions. These data clearly suggest that nursing care did make a difference
      in patient outcomes.

PMID- 12500413
TI  - The relationship between nurse staffing models and patient outcomes: a
      descriptive study.
AB  - In an era of dwindling reimbursement and rising healthcare costs, the impact of
      nurse staffing models on patient outcomes is a key concern. This study used a
      descriptive comparison design to examine the effects of a change in the staffing
      model on length of stay, variable cost, patient satisfaction, incidence of
      urinary tract infection and penumonia, and pain management in bowel resection
      patients. There were significant differences in the pain management outcomes
      between the two staffing models. Other patient outcomes were comparable despite
      decreasing the total number of caregivers on the unit. Recommendations for
      further research are discussed.

PMID- 12500414
TI  - Effect of a behavioral nursing intervention on long-term lipid regulation.
AB  - Reduction of dietary fat intake and increased physical activity are first-line
      interventions for elevated total serum cholesterol (TC) and low-density
      lipoprotein (LDL) serum cholesterol, which are major and modifiable risk factors
      for coronary heart disease. This retrospective study reports on the effects of a
      nurse-managed behavioral intervention (NMBI) program on TC and LDL levels in
      hyperlipidemic patients. Survival analysis indicated that NMBI patients had a
      significantly higher probability of attaining normal TC and LDL levels than did
      patients who received only standard nursing care. Additional analysis showed that
      actual TC and LDL values declined significantly across the study period with
      marginally significant group by time interactions. These findings provide
      preliminary evidence of the effectiveness of the behavioral intervention program
      with hyperlipidemic patients.

PMID- 12500415
TI  - Partnering for congestive heart failure: a clinic without walls.

PMID- 12500416
TI  - [Adaptation in properties of skeletal muscle to coronary artery
      occlusion/reperfusion in rats].
AB  - The present study was designed to determine if changes in function and metabolism
      of heart muscle induce alterations in characteristics of skeletal muscle. We
      investigated the histochemical and biochemical properties of soleus (SOL) and
      extensor digitorum longus (EDL) muscles in Wistar rats at the chronic phase after
      coronary artery occlusion/reperfusion. The size of myocardial infarct region was
      evaluated using a high resolution pinhole single photo emission computed
      tomography (SPECT) system. 4 wk after left coronary artery occlusion/reperfusion,
      the SOL and EDL of hindlimb were dissected out and immersed in isopentane cooled
      with liquid nitrogen for subsequent histochemical and biochemical analysis. From
      SPECT imaging, the blood circulation was recovered, but the recovery of fatty
      acid metabolism was not observed in infarct region of heart. Citrate synthase
      (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) activities in infarct region of
      heart were lower in the myocardial infarction (MI, n = 6) group compared with
      that of age-matched sham-operated (Sham, n = 6) group. In addition, heart muscle
      hypertrophy caused by the dysfunction in MI group was observed. In skeletal
      muscle, the atrophy and transition of fiber type distribution in MI group,
      reported in previous studies of heart failure, were not observed. However, the
      succinate dehydrogenase (SDH) activity in the slow twitch oxidative (SO) from SOL
      of MI group decreased by 9.8% and in the fast twitch oxidative glycolytic fibers
      (FOG), 8.0% as compared with sham group. Capillary density of the SO fibers from
      SOL of MI group also reduced by 18.5% and in the FOG fibers, 18.2% as compared
      with Sham group. Decreased capillary density in this study related significantly
      to decreased SDH activity of single muscle fibers in chronic phase of perfusion
      after surgical infarction. Our results make it clear that there is a difference
      in the reaction of skeletal muscle to coronary artery occlusion/reperfusion
      compared with chronic heart failure. However, our data would support the notion
      that there is a linkage between the function of heart and physiological
      properties of skeletal muscle.

PMID- 12500417
TI  - Moving programs from good to great.

PMID- 12500418
TI  - The echo lab: advantages and considerations of going digital.

PMID- 12500419
TI  - Enhanced external counterpulsation--a therapeutic option for patients with
      chronic cardiovascular problems.
AB  - EECP is a non-invasive outpatient treatment for cardiovascular disease refractory
      to medical and/or surgical therapy. It has been cleared by the Food and Drug
      Administration for the treatment of a variety of cardiac conditions including
      congestive heart failure and chronic stable angina. A course of therapy consists
      of 35 one-hour treatments given once or twice daily. Augmented diastolic pressure
      and retrograde flow improve myocardial perfusion, while systolic unloading
      reduces cardiac workload and oxygen requirements. As a result of this treatment,
      most patients experience increased time to onset of ischemia, increased exercise
      tolerance, a reduction in the number and severity of anginal episodes, and
      improved quality of life. Evidence has been presented that this effect lasts well
      beyond the immediate post-treatment period with some patients symptom-free for
      several years. Because patients principally seek medical care to live longer or
      feel better, heart programs need to offer their patients the latest medical
      advances which have the potential of improving patient survival and health status
      (symptoms, functioning, and quality of life). Heart programs face a challenging
      economic future. Increased competition makes it necessary to implement strategies
      for market differentiation. Those programs most attuned to what their patients
      define as critical to quality would be most likely to succeed. Over the past
      decade, there have been a growing number of patients with chronic angina who have
      exhausted the standard revascularization armamentarium. Because coronary artery
      bypass grafts occlude and restenosis occurs at angioplasty sites, many patients
      no longer have suitable coronary anatomy for additional procedures. Also, as the
      population ages, the proportion of patients with diffuse coronary disease,
      congestive heart failure, significant co-morbid illness, and poor functional
      status increases. The incapacitating effects of angina on patients' abilities to
      work, maintain regular social interactions, and participate in the usual
      activities of daily living are well described. In spite of the ongoing successes
      of catheter-based revascularization techniques, the population of patients with
      intractable angina continues to grow; and ironically, advancements in medical
      therapy have resulted in an increasing number of patients who are living with
      severe left ventricular dysfunction and congestive heart failure. Recent studies
      have estimated that approximately 5-15% of patients undergoing coronary
      angiography may be considered to have advanced coronary artery disease.
      Considering that 1,713,000 cardiac catheterizations were performed in 1996 in the
      United States, approximately 100,000-250,000 patients per year may be eligible
      for newer treatments for coronary artery disease. More recent statistics in the
      AHA Heart and Stroke Update report that in 2001, nearly one million patients had
      coronary artery bypass graft surgery or percutaneous coronary intervention,
      (Figure 1). Of these, 125,650 patients experienced persistent angina.

PMID- 12500420
TI  - [Chronic interstitial nephritis induced by 5-aminosalicylic acid: a new case
      report].
AB  - 5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel
      disease is known to induce chronic interstitial nephritis (CIN). However, the
      frequency of occurrence and the spectrum of severity of 5-ASA-induced CIN are not
      known. In this paper, we report a new case of CIN induced by 5-ASA in a patient
      treated for about 7 years for a Crohn disease. After that 5-ASA was discontinued
      and prednisone therapy started, renal function improved partially. About 30
      observations of CIN induced by the use of 5-ASA in patients treated for
      inflammatory bowel disease have already been published. None were published in
      patients treated for other diseases such as arthritis rheumatism. The review of
      the literature suggests that the prognosis is poor and correlates with the
      duration of treatment, the cumulative dose and the level of renal impairment at
      diagnostic. We believe that the control of the renal function in patients treated
      by 5-ASA must be regular and prolonged.

PMID- 12500421
TI  - [Advanced glycosylation end products (AGE): new toxins?].
AB  - Advanced glycation end-products (AGEs) are found in excess during diabetes
      mellitus, uremia and aging. Non enzymatique glycation, glycoxidation with glucose
      auto-oxidation and the polyol pathway are involved in the production of AGEs.
      Tissue accumulation of AGEs and their binding to cell receptors are critical
      steps in the deleterious consequences of AGE excess. AGE-receptor interaction
      altered endothelial cells, macrophages, mesangial and mesothelial cell functions.
      AGEs appear to be involved in the genesis of diabetic micro but also macro
      angiopathy. Reduction of AGE clearance and permanent oxidative stress are
      responsible for AGE excess during uremia. High-flux hemodialysis and peritoneal
      dialysis reduce AGE level but kidney transplantation is the best treatment to
      restore homeostasis. New drugs are tested to reduce AGEs or AGE deleterious
      effects but the best treatment remains the prevention of AGE formation by a
      strict glycemic control.

PMID- 12500422
TI  - [Cardiovascular disease in terminal end-stage renal failure--epidemiological
      aspects].
AB  - Cardiovascular disease is the leading cause of death in patients with ESRF.
      Cardiovascular mortality is 10- to 30-fold higher in ESRF patients than in the
      general population after adjustment for age, gender, ethnic origin and diabetes.
      Left ventricle hypertrophy, heart failure, and arterial atheroma are the main
      causes of cardiovascular morbidity-mortality. Among the classical cardiovascular
      risk factors identified in the Framingham study, only male gender, Caucasian
      ethnic origin, diabetes, and smoking are found in dialysis patients. Systolic
      blood pressure and total cholesterol are not associated with cardiovascular
      morbidity-mortality in the dialysis population. Inversely, low systolic pressure
      and serum cholesterol are risk factors for death. Since the classical risk
      factors are insufficient to explain the high cardiovascular morbidity-mortality
      in the dialysis population, factors related to CRF and its treatment have been
      proposed. These factors include hydroelectrolytic disorders, anemia, elevated
      Lp(a) and homocysteine, a state of micro-inflammation, and elevated
      thrombogenesis factors. Strategies designed to identify and prevent
      cardiovascular risk factors in the dialysis population should take into
      consideration the classical risk factors as well as specific risk factors related
      to CRF, and this well before reaching the state of ESRF.

PMID- 12500423
TI  - [Recent approaches to the pathogenesis of minimal change nephrotic syndrome].
AB  - Clinical and experimental observations suggest that lipoid nephrosis (Minimal
      change nephrotic syndrome) results from T cell dysfunction due to still unknown
      mechanisms. By substractive screening library, we identified 84 transcripts, of
      which 42 correspond to known genes, 12 match with proteins of yet unknown
      function and 30 are unknown clones. Among the 42 known transcripts, at least 18
      are closely involved in the T-Cell Receptor mediated signaling cascades. This
      includes genes encoding components of the T-Cell Receptor and proteins associated
      with the cytoskeleton scaffold, as well as transcription factors. During the
      relapse phase, we have detected very low levels of IL12R beta 2 mRNA suggesting
      that the T-cell activation evolves toward a Th2 phenotype. Thus, the combination
      of substractive cloning and differential screening constitutes an efficient
      approach to identify genes likely involved in the pathophysiology of MCNS.

PMID- 12500424
TI  - [Role of the CESAR protocol: treatment of visceral Henoch-Schonlein purpura].

PMID- 12500425
TI  - Identification and characterization of the peptidic component of the
      immunomodulatory glycoconjugate Immunoferon.
AB  - Inmunoferon is a glycoconjugate of natural origin, formed by the noncovalent
      association of a protein from Ricinus communis and a polysacharidic moiety, and
      endowed with immunomodulatory as well as pharmacological activities. This study
      investigated the nature of polypeptidic component of Inmunoferon. Through
      biochemical procedures and comparison with protein databases, the isolated
      protein was identified as the processed form of the seed of Ricinus communis 2S
      storage polypeptide, which has been termed RicC3. Further analysis of the
      isolated protein has revealed that it is composed of two different subunits,
      alpha and beta, which form an heterodimer of high stability and resistance to
      denaturation, acidic pH and proteolytic cleavage. These findings confirm the
      excellent properties of the product after oral administration and provide
      additional support for the pharmacological activities of Inmunoferon.

PMID- 12500426
TI  - System approach to modeling metabolite formation from parent drug: a working
      example with methotrexate.
AB  - The aim of this methodological study was to present and exemplify a system
      approach-based technology in modeling the formation of the metabolite from the
      parent drug. To represent this process, the parent-metabolite dynamic system was
      defined in such a way that the concentration-time profile of the parent drug was
      considered the input, while the concentration-time profile of the metabolite the
      output, of this system. The system-approach-based modeling technology was used to
      determine the model of the parent-metabolite dynamic system and to obtain the
      model-based estimates of the rate of metabolite formation, the rate of metabolic
      ratio and the mean time of metabolite formation. The technology was applied to
      concentration data for methotrexate and 7-hydroxymethotrexate in patients with
      psoriasis after a single oral methotrexate dose. Third-order linear models were
      selected as optimal to approximate the parent-metabolite dynamic systems
      representing the formation of 7-hydroxymethotrexate from methotrexate of these
      patients. The model-based estimates of the metabolic ratios ranged from 0.53 to
      0.95. The model-based estimates of the mean times of formation of 7
      hydroxymethotrexate from methotrexate ranged from 9.13 to 25.13 h. The model
      based estimates of the rates of formation of 7-hydroxymethotrexate from
      methotrexate reached peak values (ranging from 0.03 to 0.11 h-1) in the time
      interval 1.5-4.5 h after administration of methotraxate. This study does not only
      introduce the method that may be useful in gaining insight into metabolite
      formation, but also presents a new example of the methodological, conceptual and
      computational uniformity of the system-approach-based technology in modeling
      various biomedical systems.

PMID- 12500427
TI  - Suppression of viability and acetyl-LDL metabolism in RAW 264 macrophage-like and
      smooth muscle cells by bisphosphonates in vitro.
AB  - Etidronate and clodronate are bisphosphonates that inhibit the development of
      experimental atherosclerosis. Etidronate decreases the intimamedia thickness of
      carotid artery even in man. Liposome-encapsulated bisphosphonates inhibit the
      cellular metabolism of atherogenic, modified low-density lipoprotein (acetyl-LDL)
      by cultured macrophages. In the present study, the effects of new bisphosphonate
      tiludronate and nitrogen-containing bisphosphonate alendronate on cell viability
      and cellular uptake and degradation of acetyl-LDL were investigated in vitro with
      macrophages and arterial smooth muscle cells, which have a significant role in
      atherogenesis. Tiludronate and alendronate decreased the viability of RAW 264
      macrophages at high concentration (1,000 microM; p < 0.05), while liposome
      encapsulated drugs suppressed the viability at concentrations of 30-300 microM.
      At concentrations greater than or equal to 10 microM, tiludronate and alendronate
      inhibited the uptake and degradation of acetyl-LDL by RAW 264 cells in a
      concentration-dependent manner (p < 0.001). None of the bisphosphonates affected
      the viability of smooth muscle cells, and none but alendronate at a high
      concentration (1,000 microM) inhibited the uptake and degradation of acetyl-LDL
      by smooth muscle cells. The results show that tiludronate and alendronate inhibit
      the atherogenic activity of macrophages in vitro, as shown previously with
      etidronate and clodronate, providing further evidence for the antiatherogenic
      effects of bisphosphonates.

PMID- 12500428
TI  - Toxicological study of a new maintenance fluid, Veen 3G, in rats.
AB  - A study of the different volume and infusion rates of a new maintenance fluid,
      Veen 3G, on the general conditions of rats was investigated during the 14 days
      after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused
      at a rate of 300 ml/kg/h in male and female rats. Results were compared with
      those for Gurunon Ringer solution (GRS) in male and female rats. We observed only
      transient polyuria in animals administered by each dose of Veen 3G and GRS for 0
      15 min after infusion. Necropsy was not observed in any of the animals tested 14
      days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates
      of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h,
      irregular respiration and decrease in movement were observed concomitantly with
      polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a
      rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In
      this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less
      than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than
      that used clinically in maintenance treatment, Veen 3G is suggested to be safe,
      with the exception of polyuria, in clinical situations at the standard infusion
      rate (5-15 ml/kg/h).

PMID- 12500429
TI  - Pyrogallol-induced hepatotoxicity in rats: a model to evaluate antioxidant
      hepatoprotective agents.
AB  - Various hepatic disorders and hepatotoxic agents are associated with increased
      free radical generation. In the present study, the free radical generator
      pyrogallol (100 mg/kg i.p.) caused significant hepatic damage. The serum enzymes
      asparatate aminotransaminase (AST) and alanine aminotransaminase (ALT) increased
      to 357 +/- 30.7 IU/I and 147.8 +/- 28.4 IU/I, respectively in the pyrogallol
      treated group compared with 208.4 +/- 4.1 IU/I and 84.5 +/- 19.5 IU/I,
      respectively in the control rats. Compared with control rats, the liver tissue in
      the pyrogallol-treated group showed an increased level of malondialdehyde (MDA)
      as well as glutathione (GSH). The infiltration of white blood cells into the
      liver tissue, as seen histologically, further substantiated liver damage.
      Pretreatment with a standard hepatoprotective drug (silymarin, 100 mg/kg i.p.)
      afforded significant protection against pyrogallol hepatotoxicity, as evidenced
      by amelioration of the raised serum markers of hepatic function, markers of
      oxidative stress and normal liver histology. Thus, pyrogallol-induced
      hepatotoxicity could be used as an appropriate model to evaluate hepatoprotective
      agents that have an antioxidant property.

PMID- 12500430
TI  - P-glycoprotein-mediated efflux as a major factor in the variance of absorption
      and distribution of drugs: modulation of chemotherapy resistance.
AB  - Active efflux of many therapeutics and other xenobiotics from cells and tissues
      by P-glycoprotein (P-gp) can cause dramatic effects on bioavailability. This
      expulsion of compounds from cells is known as a major form of multiple drug
      resistance (MDR). Often a significant barrier to oral absorption at the
      intestine, P-gp also protects the liver, brain, placenta, testes, adrenal gland
      and other tissues from cytotoxic insult. Due to the wide tolerance of substrate
      recognition, P-gp can often be the mechanism for significant pharmacokinetic drug
      interactions when two or more drugs are competing for the P-gp transport site. P
      gp levels are also inducible and can be even further elavated in cancer cells,
      thus contributing to the confounding pleiotropic resistance to chemotherapy and
      poor treatment prognosis. Consequently, a broad scope of research over 20 years
      has led to the evaluation of co-therapies intended to augment chemotherapy by
      inhibiting P-gp. This review includes a list of the currently known P-gp
      inhibiting adjuvant candidates described in the literature, with associated
      references and summary data. The summary catalogue of P-gp modulators illustrates
      the ardent pursuit to overcome this form of therapy resistance and gives examples
      of clinical success and failure.

PMID- 12500431
TI  - Experimental approaches to study PPAR gamma agonists as antidiabetic drugs.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors that are
      related to retinoid, steroid and thyroid hormone receptors. Since PPARs appear to
      be closely involved in the regulation of dietary fat storage and catabolism, they
      have been established as an important target for the treatment of type 2 diabetes
      and other disorders associated with the high intake of dietary fat.
      Thiazolidinediones (TZDs) were the first class of compounds to be identified as
      PPAR gamma-ligands, constituting a new class of antidiabetic drugs that have
      recently been introduced as therapeutic agents for the treatment of type 2
      diabetes mellitus by acting as insulin sensitizers. These compounds improve
      insulin resistance by increasing cell sensitivity to insulin. In fact, PPAR gamma
      agonists increase peripheral insulin sensitivity by increasing the transcription
      of genes, which, in turn, increase glucose uptake, also improving insulin
      stimulated glucose disposal in muscle. PPAR gamma agonists increase insulin
      signaling, reduce circulating levels of free fatty acids and stimulate adipocyte
      differentiation, thus favoring the formation of smaller, more insulin-sensitive
      adipocytes. TZDs have been proven effective in different experimental models to
      evaluate their effectiveness as an antidiabetic agent, and the involvement of
      PPAR gamma in the pharmacological effects of these compounds has been supported
      by studies showing an excellent correlation between the hypoglycemic action of
      these drugs and their affinity for PPAR gamma. Despite this evidence, the site of
      action and the molecular mechanism of TZDs remain unclear. The aim of the present
      article was to review and discuss the most relevant pharmacological studies
      performed in the search for establishing the mechanism of action of antidiabetic
      TZDs and related compounds acting as PPAR gamma agonists, as well as to summarize
      those representative experimental approaches currently used to evaluate PPAR
      gamma agonists as therapeutic agents for the treatment of insulin-resistant type
      2 diabetes mellitus.

PMID- 12500432
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: Abacavir sulfate, abciximab,
      acetylcysteine, adefovir dipivoxil, alfuzosin hydrochloride, aliskiren fumarate,
      alosetron hydrochloride, amlodipine besilate, apomorphine hydrochloride,
      atazanavir, atorvastatin, atorvastatin calcium, atrasentan; Basiliximab,
      beraprost sodium, bevacizumab, bivalirudin, botulinum toxin type A, botulinum
      toxin type B; Celecoxib, cetuximab, cilansetron, cilomilast; Daclizumab,
      darbepoetin alfa, docetaxel, duloxetine hydrochloride; Efalizumab, efavirenz,
      eletriptan,, entecavir, eplerenone, epoetin alfa, eptifibatide, esomeprazole
      magnesium. ezetimibe; Filgrastim, finasteride, fluvastatin sodium, follitropin
      alfa; Gemcitabine, gemeprost, ghrelin (human); HE-2000; Infliximab, 111In
      Pentetreotide, interferon alfa-2 alpha, interferon alfa-2 beta, interferon beta-1
      alpha, irbesartan, irinotecan hydrochloride; Ketamine hydrochloride; L-778123,
      lafutidine, lamivudine, lamivudine/zidovudine, latanoprost, letrozole,
      licofelone, lopinavir, losartan potassium, loxiglumide, lubeluzole; Magnesium
      sulfate, MeGLA, meloxicam, mycophenolate mofetil; NBI-6024, nelfinavir mesilate,
      nesiritide, nevirapine, niacin, NN-2211; Octreotide, orlistat; PC-515,
      peginterferon alfa-2 alpha, peginterferon alfa-2b, pemetrexed disodium,
      pibrozelesin hydrochloride, pimagedine, pirfenidone, pitavastatin calcium,
      premarin/trimegestone, prucalopride; Rabeprazole sodium; reboxetine, risedronate
      sodium, ritonavir, rituximab, rofecoxib, roflumilast, rosuvastatin calcium;
      Sertraline, sibutramine hydrochloride monohydrate, sildenafil citrate,
      spironolactone, stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride,
      tenecteplase, thalidomide, travoprost; Valsartan; Zoledronic acid monohydrate.

PMID- 12500433
TI  - [Behavioral symptoms in preschool children at the time of school entrance from
      the perspective of parents--data regarding prevalence and risk factors in an
      epidemiological study].
AB  - Behavioral and emotional problems based on parents information from the Child
      Behavior Checklist (CBCL) were investigated in a large epidemiological sample of
      4363 six year old pre-school children from the area of Heidelberg and Rhein
      Neckar county. An overview about symptom frequencies of boys and girls is given,
      taking age specific evaluations into account. Considering symptoms and syndromes,
      externalizing and attention problems show high prevalence, especially for boys.
      Family problems are the most important predictors of child global symptomatology,
      explaining about 10% of variance of the CBCL total score. Other factors like
      gender, chronical illness, adverse living conditions, family constellation or
      amount of TV consumption prove as additional independent predictors. An overall
      model explains about 20% of variance of child symptomatology. Results are
      discussed from the view of normal child development, developmental
      psychopathology, changing norms and altered socio-cultural conditions.

PMID- 12500434
TI  - [Development of body image in adolescence].
AB  - In a prospective study the development of body experience in adolescence and
      associations with psychosocial characteristics as well as development of symptoms
      were investigated. Body experience, physical and psychological well-being as well
      as sense of coherence were assessed three times over the course of 18 months in
      325 male and female adolescents aged 16-19 years. During the course of the study
      the participants reported an improvement of their body experience. Female
      adolescents reported at all assessment times lower levels of attractiveness/self
      confidence and higher levels of insecurity/worry than males. Body experience,
      physical and psychological well-being as well as sense of coherence were closely
      associated with each other. The results indicate that body experience generally
      consolidates during the course of adolescence. However, the development on
      individual levels can vary considerably. The body experience reflects the
      physical and psychosexual development as well as the adolescents' well-being.
      Thus, more consideration should be given to body experience in therapies with
      adolescents who suffer from psychosomatic illness.

PMID- 12500435
TI  - [Treatment motivation, treatment satisfaction and quality of life from the
      viewpoint of parents at a child psychiatry facility--contribution to quality
      assurance].
AB  - This study tried to figure out if parents initial treatment motivation influenced
      their final assessment of the treatment process and its outcome in child
      psychiatry. We evaluated parents therapy motivation by developing a questionnaire
      based on solution focussed therapy's conception of motivation of clients (Berg
      1992). The change during the treatment in parents satisfaction with their life
      situations and their experience of pressure ("life quality")--independent from
      their pronounced assessment of the quality of therapy--was taken as one
      indication of treatment quality. In addition to this parents' assessment of
      treatment was investigated by a questionnaire for therapy evaluation which
      included process and outcome quality factors. There could be shown that
      significant relations existed. Therefore we are convinced that the discussion of
      quality assurance in child psychiatry should be enlarged with a methodical
      conception of therapy motivation and the assessment of life quality of parents in
      addition to the evaluation of their specific therapy satisfaction.

PMID- 12500436
TI  - [Adolescent psychiatry addiction centers--necessary and effective? Treatment
      follow-up of adolescent psychiatric treatment and rehabilitation for adolescent
      drug addicts].
AB  - 194 patients who were referred to adolescent psychiatry inpatient unit (98) and a
      drug rehabilitation unit (96) in 1999 and 2000 were compared as to
      sociodemographic variables, comorbidity and course of treatment. Female patients
      were overrepresented in the psychiatry unit, whereas in the rehab unit more
      immigrants or referrals from juvenile detention were treated. Most psychiatry
      patients were comorbid with at least one, a quarter with more than one additional
      diagnosis and had less polysubstance dependence (69%). Due to a drop out rate of
      71% in the patients with a criminal justice status, rehab patients did not
      complete treatment as often as psychiatry patients. Three years after their first
      dismissal and, in some cases, after several new admissions, 60% of rehabilitation
      clients completed the program. Both settings have their own right in the system
      because comorbid patients need highly individualized therapy, and rehab patients
      need programs able to address school-based, family-related, and gender-specific
      issues.

PMID- 12500437
TI  - Planetree: a return to our roots.

PMID- 12500438
TI  - Catastrophic coverage only.

PMID- 12500439
TI  - Coverage and access. Last gasp for single payer?

PMID- 12500440
TI  - Ethics. Rules of the road.

PMID- 12500441
TI  - Employee satisfaction. Vying for health.

PMID- 12500442
TI  - Leadership. Not for men only.

PMID- 12500443
TI  - Management. Playing nice.

PMID- 12500444
TI  - Practical ethics. Pay differential discovered.

PMID- 12500445
TI  - "Home" improvement. Comfort, safety and privacy emerge as the biggest
      considerations in hospital design and construction.

PMID- 12500446
TI  - Building smarter EDs.
AB  - Flexibility is the name of the game as hospitals undertake radical redesigns of
      their emergency departments. Prompted by HIPAA privacy requirements and using
      innovative flow patterns, moveable walls, larger patient rooms and evolving
      technology, the new ED can adapt quickly to handle fluctuating patient loads and
      potential terrorist attacks.

PMID- 12500447
TI  - Translation, por favor.
AB  - Spanish is the first language of a fast-growing proportion of the U.S.
      population, and not just in traditional areas such as certain big cities and
      southern border states. Hospitals in nearly every region of the country are
      scrambling to find ways to communicate with these patients better to avert
      medical errors, enhance the patient experience and adhere to federal Civil Rights
      laws. One key consideration: It's not advisable to rely on patients' family
      members to serve as translators; to avoid liability problems and safety concerns,
      interpreters must have experience in the delivery of health care and should be
      certified to provide Spanish translation.

PMID- 12500448
TI  - Risks and rewards. Integrating CAM services into the traditional mix brings
      challenges--and opportunities.

PMID- 12500449
TI  - HIPAA: the patient privacy challenge.
AB  - The HIPAA privacy rule, slated to take effect in April, guarantees patients
      access to their medical records, gives them more control over how their health
      information is used and disclosed, and provides recourse if their privacy is
      compromised. Providers need to understand their responsibilities and rights. Our
      fold-out guide will help providers understand the rule so that new policies and
      procedures can be implemented without interfering with access to quality care.

PMID- 12500450
TI  - Potential association between male infertility and occupational psychological
      stress.
AB  - The purpose of this work was to investigate the influence of working conditions,
      occupational exposures to potential reproductive toxic agents, and psychological
      stress on male fertility. The study population consisted of 202 consecutive male
      patients attending a fertility clinic. Of those, 106 patients had attended the
      clinic because of a male infertility problem (case group), 66 patients had
      attended the clinic because of a female infertility problem (control group), and
      30 patients had a combined infertility problem (male and female). Male
      infertility was associated with working in industry and construction as compared
      with other occupations (78.6% vs 58.3%, P = 0.044). Industry and construction
      workers were of lower educational level than the other workers (mean: 12.1 vs
      13.4 years, P = 0.021). These patients also tended to smoke more than the other
      workers (OR = 2.53, 95% CI = 1.08 to 5.98), more often worked in shifts (OR =
      3.12, 95% CI = 1.19 to 8.13), reported physical exertion in work (OR = 3.35, 95%
      CI = 1.44 to 7.80), and were more exposed to noise and welding (OR = 3.84, 95% CI
      = 1.63 to 9.14, OR = 4.40, 95% CI = 1.11 to 1.76, respectively). Male infertility
      (case group) was found to be statistically related to higher marks in all four
      measures of burnout as compared with the controls. The largest difference was
      obtained in the measure of cognitive weariness (mean: 2.9 vs 2.1, P < 0.001). In
      a multiple logistic regression analysis, industry and construction jobs (adjusted
      OR = 2.2, 95% CI 1.2 to 2.7) and cognitive weariness (adjusted OR = 1.8, 95% CI =
      1.03 to 4.6) were found to be independent risk factors for male infertility
      problems. Male infertility was independently associated with industry and
      construction jobs as well as job burnout.

PMID- 12500451
TI  - The effect of a health care management initiative on reducing workers'
      compensation costs.
AB  - The effect of both a cost control and health care management initiative (HCMI) on
      Workers' Compensation costs at a self-insured University Hospital was assessed.
      Seven cohorts of injured workers were studied. Cost control measures started in
      1993 included early return to work and injury prevention programs, internal
      administration of legal cases, and utilization of modified duty assignments. The
      health care management initiative fully in place in 1997 included aggressive case
      management and preferred provider panel utilization. Workers' Compensation
      indemnity costs and lost workdays incurred by each cohort were compared. A 41 to
      59% reduction in indemnity payments and 46 to 67% reduction in lost time cases
      were realized after the health care management initiative was fully in place.
      During this time, accepted claims were reduced by 10 to 15%. The quality of the
      provider panel, as measured by academic credentials, experience and board
      certification, did not change. Cost control measures, without comprehensive case
      management, did not decrease these parameters significantly. The health care
      management initiative realized reductions in lost time cases and Workers'
      Compensation indemnity costs.

PMID- 12500452
TI  - Office-based medical care for work-related conditions: findings from the National
      Ambulatory Medical Care Survey, 1997-1998.
AB  - Data from the 1997 and 1998 National Ambulatory Medical Care Surveys were
      analyzed to describe nationally representative patterns of office-based
      ambulatory medical care for work-related injuries and illnesses. Key dimensions
      of care included patient demographics, diagnoses, utilization of services,
      provider and payer information, and characteristics of the clinical setting in
      which care was delivered. Multivariate analyses revealed that compared to visits
      for nonwork related conditions, ambulatory care visits for work-related
      conditions are more likely to involve x-rays, injury prevention counseling, and
      physiotherapy. Surgical procedures, mental health counseling, prescription drug
      medication, and the taking of blood pressure were found to be relatively less
      common. Additionally, authorization for care was required considerably more often
      at visits for work-related conditions, and the provider for patients with work
      related conditions was less likely to be the patient's regular primary care
      physician.

PMID- 12500453
TI  - 1-hydroxypyrene as a biomarker of occupational exposure to polycyclic aromatic
      hydrocarbons (PAH) in boilermakers.
AB  - A repeated measures short-term prospective study was performed in boilermakers to
      determine occupational polycyclic aromatic hydrocarbon (PAH) exposure using the
      biomarker, 1-hydroxypyrene (1-OHP). Two work sites were studied; an apprentice
      school (metal fume exposure) and a boiler overhaul (residual oil fly ash [ROFA]
      and metal fume exposure). Pre- and postshift urine samples (n = 241; 41 male
      subjects) were analyzed for cotinine and 1-OHP. Descriptive statistics and
      generalized estimating equations were calculated. At the apprentice school cross
      shift 1-OHP levels did not significantly differ. At the overhaul 1-OHP levels
      increased during the week in smokers and nonsmokers; in nonsmokers the 1-OHP
      level increased significantly postshift compared to preshift. In conclusion this
      study suggests that boilermakers exposed to occupational particulates are exposed
      to PAH. The urinary 1-OHP level may be a useful biomarker of PAH exposure in
      boilermakers exposed to ROFA, particularly in nonsmokers.

PMID- 12500454
TI  - Association of health risks with the cost of time away from work.
AB  - The purpose of this study was to combine absences, short-term disability, and
      workers' compensation into a sum of the cost of time away from work (TAW) and
      compare it with health risk status and individual health risks of 6220 hourly
      workers at Steelcase Inc. The study used 3 years (1998 to 2000) of TAW and health
      risk appraisal data. Higher TAW costs were associated with illness days,
      drug/medication use, the individual's lower perception of physical health, job
      dissatisfaction, high stress, life dissatisfaction, and physical inactivity. More
      high-risk individuals (80.6%) had a TAW occurrence than medium- (72.8%) and low
      risk (61.1%) individuals. High-risk individuals had higher TAW costs than medium-
      and low-risk individuals. Of the total TAW costs, 36.2% was attributed to the
      excess risks of the medium- and high-risk individuals or nonparticipants compared
      with low-risk participants. If TAW costs follow risk reduction, a potential
      annual savings of $1.7 million could be achieved.

PMID- 12500455
TI  - Chronic exposure of rats to cotton-mill-room noise changes the cell composition
      of the tracheal epithelium.
AB  - The work environment of cotton mill rooms of modern textile plants is
      characterized by noise pollution. We have taped and reproduced this noisy
      environment to study its effects on experimentally exposed rats. Because we have
      previously documented that chronic noise causes alterations in the respiratory
      epithelium, we have focused our investigation on the morphology of the tracheal
      lining. Wistar rats were exposed to the textile-type noise from 1 up to 7 months,
      with an average 40 hours weekly exposure of the animals. The rats were sacrificed
      monthly and the tracheas were studied by scanning electron microscopy (SEM) to
      quantify the areas of the airway lining that were covered by ciliated, serous or
      other cells of the epithelium. We found that noise exposure of the rats caused a
      significant loss of tracheal ciliated cells; an increased density of serous cells
      on the epithelium balanced this change. This modification of the rat trachea was
      already established after 1 month of noise treatment of the animals; it did not
      change significantly throughout the 7-month course of the herein investigation.
      Loss of ciliated cells was more intense in areas of the tracheal epithelium
      located between the regions of cartilage rings. We conclude that the ciliated
      cell is an elective target for damage caused on the respiratory epithelium by the
      workplace noise occurring in cotton mill rooms. This modification of the
      respiratory epithelium is likely to impair clearance of the airways since this
      function depends on the activity of ciliated cells.

PMID- 12500456
TI  - Primary and secondary allergies to laboratory animals.
AB  - Although laboratory animal allergy (LAA) is a significant occupational hazard
      among workers exposed to laboratory animals, few studies have evaluated long-term
      risks to workers who remain in the workplace. This short-term focus has obscured
      the evaluation of subsequent animal allergies (secondary LAA). We analyzed
      surveillance data from a 10-year LAA prevention program to estimate incidence
      rates of primary and secondary LAA and to evaluate the effectiveness of the
      prevention program in reducing the development of primary LAA. The 10-year
      incidence rates of primary and secondary LAA were 1.34 (95% CI, 0.78-1.90) and 11
      (95% CI, 7.4-14.6) cases per 100 person-years, respectively. The annual incidence
      of primary LAA was reduced from 3.6% to 0 in the first 5 years and did not rise
      above 1.2% over the remaining years, whereas the incidence of secondary LAA was
      greater than 8% in most years. These findings suggest that programs effective at
      preventing primary LAA may need to be evaluated for their effectiveness at
      protecting against further risk.

PMID- 12500457
TI  - Respiratory symptoms and dust exposure among male workers in small-scale wood
      industries in Tanzania.
AB  - Few studies have assessed respiratory symptoms and dust exposure levels in small
      scale wood industry workers in Africa. We interviewed 546 workers exposed to wood
      dust and 565 control subjects using a respiratory health questionnaire. Inhalable
      dust measurements were collected for 106 workers. The dust exposure was high, and
      job title-based geometric mean exposure levels ranged from 2.9 to 22.8 mg/m3.
      Prevalence of respiratory symptoms in the previous 12 months was significantly
      higher in the exposed group compared with the nonexposed office workers. Allergy
      and sensitivity symptoms were reported regularly in the exposed group with Odds
      ratios and 95% confidence intervals (CIs) varying from 2.4 (95% CI = 1.8-3.1) for
      low- and 2.7 (1.8-4.0) for high-exposure groups compared with controls. We
      conclude that working in the small-scale wood industry in Tanzania is associated
      with an increased prevalence of respiratory symptoms.

PMID- 12500458
TI  - Disabling occupational injury in the US construction industry, 1996.
AB  - In 1996 the US construction industry comprised 5.4% of the annual US employment
      but accounted for 7.8% of nonfatal occupational injuries and illness and 9.7% of
      cases involving at least a day away from work. Information in the published
      literature on the disability arising from construction injuries is limited. The
      construction claims experience (n = 35,790) of a large workers' compensation
      insurer with national coverage was examined. The leading types and sources of
      disabling occupational morbidity in 1996 in the US construction industry were
      identified. Disability duration was calculated from indemnity payments data using
      previously published methods. The average disability duration for an injured
      construction worker was 46 days with a median of 0 days. The most frequently
      occurring conditions were low back pain (14.8%), foreign body eye injuries
      (8.5%), and finger lacerations (4.8%). Back pain also accounted for the greatest
      percentage of construction claim costs (21.3%) and disability days (25.5%).
      However, the conditions with the longest disability durations were sudden-onset
      injuries, including fractures of the ankle (median = 55 days), foot (42 days),
      and wrist (38 days). Same-level and elevated falls were the principal exposures
      for fractures of the wrist and ankle, whereas elevated falls and struck by
      incidents accounted for the majority of foot fractures. Manual materials handling
      activities were most often associated with low back pain disability. The results
      suggest that these most disabling injuries can be addressed by increasing primary
      prevention resources in slips and falls and exposures related to injuries of
      sudden-onset as well as in reducing manual materials handling and other exposures
      associated with more gradual-onset injuries.

PMID- 12500459
TI  - Pseudo-outbreak of tuberculosis in poultry plant workers, Sussex County,
      Delaware.
AB  - Delaware is a leading US poultry-producing state, and foreign-born workers make
      up a significant percentage of those employed by Delaware's poultry plants. In
      Sussex County, Delaware, a high percentage of the poultry workers are from two
      countries with a high incidence of tuberculosis (TB), Mexico and Guatemala, and
      thus are at risk for TB infection and disease. Furthermore, their risk of TB may
      be increased because many of these workers live in crowded conditions and lack
      access to medical care.

PMID- 12500460
TI  - Benzene exposure monitoring of Tunisian workers.
AB  - To monitor benzene exposure and to check reliability of urinary trans,trans
      Muconic Acid (t,t-MA) as a bio-marker of benzene exposure in local conditions, a
      study was conducted on 30 Tunisian exposed workers (20 tanker fillers and 10
      filling station attendants). The analyses were carried out on environmental air
      and urinary t,t-MA before (t,t-MAA) and at the end of work shift (t,t-MAB). 20
      nonoccupationally exposed subjects were also investigated. The average value of
      environmental benzene concentration was 0.17 ppm. The differences between t,t-MAA
      and t,t-MAB concentrations and between t,t-MAB and t,t-MA measured in controls
      (t,t-MAC) were both significant (p < 0.001). Benzene air concentrations were well
      correlated with t,t-MAB: R = 0.76. In the nonexposed group, average t,t-MA
      concentrations is significantly higher among smokers than nonsmokers (P < 0.02).
      Analysis of urinary t,t-MA offers a relatively simple and suitable method for
      benzene exposure monitoring.

PMID- 12500461
TI  - Prevalence and onset of rhinitis and conjunctivitis in subjects with occupational
      asthma caused by trimellitic anhydride (TMA).
AB  - Individuals with occupational asthma may also report symptoms of rhinitis or
      conjunctivitis. The objective of this study was to investigate the prevalence of
      rhinitis and conjunctivitis in subjects with occupational asthma as a result of
      trimellitic anhydride (TMA). Additionally, we wanted to evaluate the onset of
      rhinitis and conjunctivitis symptoms as compared with the occupational asthma
      symptoms. In a case series design, we studied 25 consecutive employees with TMA
      induced asthma; each of them had participated in an annual surveillance program
      in which they were queried about rhinitis, conjunctivitis, and other respiratory
      symptoms. Twenty-two of the 25 (88%) reported rhinitis symptoms whereas 17 of the
      25 (68%) reported conjunctivitis symptoms. In 17 of the 22 (77%) individuals with
      rhinitis and asthma, the rhinitis symptoms preceded the asthma symptoms. In 14 of
      the 17 (82%) individuals with conjunctivitis, those symptoms preceded the asthma
      symptoms. In summary, symptoms of rhinitis and conjunctivitis are common in
      subjects with occupational asthma because of TMA and often precede the
      respiratory symptoms.

PMID- 12500462
TI  - Relationship between cardiovascular disease morbidity, risk factors, and stress
      in a law enforcement cohort.
AB  - It is unclear to what extent law enforcement officers (LEOs) experience increased
      prevalence of cardiovascular disease (CVD; defined as coronary heart disease,
      myocardial infarction, angina, or stroke) and, if so, whether perceived stress
      affects this relationship. First, self-reported CVD risk factors among currently
      employed male LEOs from 9 states (n = 2818) were compared to CVD risk factors
      among similarly-aged males with similar incomes in the same states (n = 8046).
      Second, CVD prevalence was compared among LEOs (n = 1791) and similarly-aged
      males with similar incomes (n = 2575) from four of these states. Finally, among
      the LEOs only, the possible effect of perceived stress on the relationship
      between CVD prevalence and CVD risk factors was assessed. LEOs reported higher
      prevalence of hypertension, hypercholesterolemia, tobacco use, and elevated body
      mass index. CVD prevalence did not differ significantly between the LEO group and
      the general population (2.3% +/- 15% versus 3.1% +/- 17%; P = 0.095). In the LEO
      only group, the best predictors of CVD were: time in the profession (OR = 1.07;
      95% CI = 1.03-1.11), perceived stress (OR = 1.05; 95% CI = 1.00-1.10), and
      hypertension (OR = 0.33; 95% CI = 0.18-0.62). In the LEO-only group, perceived
      stress was associated with CVD (P = 0.008), and three CVD risk factors were
      significantly affected by perceived stress: cholesterol, hypertension, and
      physical activity. Perceived stress was affected by duration of time in the
      profession (P = 0.004), independent of an age effect (P = 0.353). Among
      susceptible officers, perceived stress may contribute to CVD directly and through
      potentiating several CVD risk factors.

PMID- 12500463
TI  - Different measures of asbestos exposure in estimating risk of lung cancer and
      mesothelioma among construction workers.
AB  - To analyze occupation, expert-evaluated cumulative exposure, and radiographic
      abnormalities as indicators of asbestos-related cancer risk we followed 16,696
      male construction workers for cancer in 1990-2000. We calculated standardized
      incidence ratios (SIR) in comparison to the Finnish population and relative risks
      (RR) in a multivariate analysis in comparison to the internal low-exposure
      category of each indicator. Overall, the risk was increased for mesothelioma (SIR
      2.0, 95% CI = 1.0-3.3), but not for lung cancer (SIR 1.1, 95% CI = 0.9-1.2).
      Radiographic lung fibrosis indicated a 2-fold and a high value of the exposure
      index a 3-fold RR of lung cancer, while there was no risk among those with
      pleural plaques. The risk of lung cancer was the highest in insulators (RR 3.7,
      95% CI = 1.4-9.9). Occupation, expert-evaluated cumulative exposure, and lung
      fibrosis are useful indicators of lung cancer risk among construction workers.

PMID- 12500464
TI  - Evaluation of self-reported skin problems among workers exposed to toluene
      diisocyanate (TDI) at a foam manufacturing facility.
AB  - Toluene diisocyanate, or TDI (CAS 584-84-9) is a well-known asthmagen and
      respiratory irritant. TDI is also known for its ability to irritate the skin and
      mucous membranes. To further investigate the dermal effects of TDI, NIOSH
      investigators conducted a cross-sectional study at a flexible foam manufacturing
      plant. A total of 114 workers participated in the study. Participants completed a
      medical questionnaire, provided blood for antibody testing to TDI and other
      allergens, and a subset of participants reporting skin symptoms underwent skin
      patch testing to a standard diisocyanate panel. Production line workers were more
      than twice as likely to report skin problems as those working in nonproduction
      areas (PRR = 2.66; 95% CI = 1.14-16.32; P = 0.02). Age, gender and duration of
      employment at the plant were comparable among participants working in production
      and nonproduction areas. Of the 100 participants who provided blood samples for
      antibody testing, specific IgG antibody to TDI was detected in two individuals,
      and none of the samples demonstrated specific IgE antibody to TDI. Of the 26
      workers who underwent skin patch testing, none developed reactions to the
      diisocyanate allergens. These results suggest that the skin symptoms among study
      participants represent an irritant rather than an immunologic reaction to TDI, or
      to an unidentified allergen present in the foam.

PMID- 12500465
TI  - Long-term follow-up study on patients with vibration-induced white finger (VWF).
AB  - The prognosis of vibration-induced white finger was investigated with a long
      follow-up period. From 1975 to 1994, 99 men with hand-arm vibration syndrome who
      received the annual compulsory examination at San-in Rosai Hospital were followed
      up for 15 years or longer. Based on the extent of finger-blanching attacks
      described in the medical records, they were classified according to the vascular
      stage of the Stockholm workshop scale. In our laboratory, finger systolic blood
      pressure (FSBP) measurement after finger cooling has been performed since 1989.
      We compared the stage classification with the results of FSBP measurement after
      finger cooling in the period 1989-1994. The stage 2 and stage 3 groups showed a
      significant decrease in FSBP% compared with the stage 0 group. The vascular stage
      classification based on subjective symptoms in this study was to a certain extent
      reliable. Although vibration-induced white finger symptoms tended to improve to
      some extent, 43.2% and 70.4% of patients with stage 2 and stage 3 at first
      examination, respectively, still suffered from finger blanching attacks after 15
      years of observation. Blanching of fingers in advanced stages, especially stage
      3, was found to be persistent many years after cessation of vibration exposure.

PMID- 12500466
TI  - Provider- and plan-specific measures of quality.

PMID- 12500467
TI  - Achieving improvement through nursing home quality measurement.
AB  - CMS has initiated the Nursing Home Quality Initiative (NHQI) to improve the
      quality of nursing home care. Central to the NHQI is the public reporting of
      nursing home quality measures that serve as the basis for the Initiative's
      communication and quality improvement program. This article provides an overview
      of the NHQI, focusing on the role of nursing home quality measures in achieving
      improvements in nursing home care. We also describe the evolution of quality
      measurement in nursing homes, a recent CMS project to improve measures through
      risk adjustment and other refinements, the use of these measures in a pilot of
      the NHQI, and the lessons learned for future work in this area.

PMID- 12500468
TI  - Identification and evaluation of existing nursing homes quality indicators.
AB  - We summarize work done to identify and evaluate existing quality indicators (QIs)
      for long-term care (LTC) settings. Indicators operationally defined using
      routinely collected and computerized patient assessments were identified and then
      aggregated to characterize the performance of the nursing facility over a
      specific period of time. Of 143 indicators reviewed, only 22 were recommended for
      use in comparing performance across facilities. Conceptual and technical issues
      influence the appropriateness of QIs for different audiences.

PMID- 12500469
TI  - Developing dialysis facility-specific performance measures for public reporting.
AB  - The Balanced Budget Act (BBA) of 1997 directed CMS to implement a system to
      measure and report the quality of dialysis services under Medicare by 2000.
      Because of this tight timeframe, a rapid-cycle measurement development process
      was initiated to develop dialysis facility-specific measures that could be
      released to the public. The result was "Dialysis Facility Compare" which has
      served as a template for the development of public reporting initiatives for
      other providers in the Medicare Program. This article describes the process used
      for developing and reporting these performance measures and the lessons learned
      for future work in this area.

PMID- 12500470
TI  - Public reporting of hospital patient satisfaction: the Rhode Island experience.
AB  - This article describes a collaborative process for legislatively mandated public
      reporting of health care performance in Rhode Island that began with hospital
      patient satisfaction. The goals of the report were both quality improvement and
      public accountability. Key features addressed include: the legislative context
      for public reporting; widespread participation of stakeholders; the structure for
      decision making; and the use of formative testing with cognitive interviews to
      get responses of consumers and others about the report readability and
      comprehensibility. This experience and the lessons learned can guide other States
      considering public reporting on health care performance.

PMID- 12500471
TI  - Quality improvement in a primary care case management program.
AB  - In this article we describe and evaluate quality monitoring and improvement
      activities conducted by Massachusetts Medicaid for its primary care case
      management program, the primary care clinician plan (PCC). Emulating managed care
      organization (MCO) practices, the State uses claims to analyze and report service
      delivery rates on the practice level and then works directly with individual
      medical practices on quality improvement (QI) activities. We discuss the value
      and limitations of claims-based data for profiling, report provider perspectives,
      and identify challenges in evaluating the impact of these activities. We also
      provide lessons learned that may be useful to other States considering
      implementing similar activities.

PMID- 12500472
TI  - Variation in patient-reported quality among health care organizations.
AB  - Health care quality measurement initiatives often use health plans as the unit of
      analysis, but plans often contract with provider organizations that are managed
      independently. There is interest in understanding whether there is substantial
      variability in quality among such units. We evaluated the extent to which scores
      on the Consumer Assessment of Health Plans Study (CAHPS) survey vary across:
      health plans, regional service organizations (RSOs) (similar to independent
      practice associations [IPAs] and physician/hospital organizations [PHOs]),
      medical groups, and practice sites. There was significant variation among RSOs,
      groups and sites, with practice sites explaining the greatest share of variation
      for most measures.

PMID- 12500473
TI  - Combining health plan performance indicators into simpler composite measures.
AB  - We investigated how the Consumer Assessment of Health Plan Study (CAHPS) survey
      and the Health Plan Employer Data Information System (HEDIS) measures from
      Medicare managed care (MMC) plans could be combined into fewer summary
      performance scores. Four scores summarize most of the variability in these
      measures, representing (1) care at the doctor's office, (2) customer service and
      access, (3) vaccinations, and (4) clinical quality measures. These summaries are
      substantively interpretable, internally consistent, and describe the majority of
      variation among units in the performance scores analyzed.

PMID- 12500474
TI  - Combining HEDIS indicators: a new approach to measuring plan performance.
AB  - We developed a new framework for combining 17 Health Plan Employer Data and
      Information Set (HEDIS) indicators into a single composite score. The resultant
      scale was highly reliable (coefficient alpha = 0.88). A principal components
      analysis yielded three components to the scale: effectiveness of disease
      management, access to preventive and followup care, and achieving medication
      compliance in treating depression. This framework for reporting could improve the
      interpretation of HEDIS performance data and is an important step for CMS as it
      moves towards a Medicare managed care (MMC) performance assessment program
      focused on outcomes-based measurement.

PMID- 12500475
TI  - Strategies for Medicare health plans serving racial and ethnic minorities.
AB  - The Medicare Managed Care (MMC) Consumer Assessment of Health Plans Study (CAHPS)
      survey offers an opportunity to examine differences in health plan experiences
      and patterns of use of services of racial and ethnic minority beneficiaries
      enrolled in health plans. Analysis of the survey data and review of prior
      literature indicate significant health disparities and different patterns of
      health care use by racial and ethnic minorities. Improved measurement of health
      plan performance in serving minority enrollees, and development of performance
      improvement strategies, could have the potential to reduce the observed health
      disparities.

PMID- 12500476
TI  - Ryan White CARE Act and eligible metropolitan areas.
AB  - Title I of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act
      provides emergency assistance to eligible metropolitan areas (EMAs) to provide a
      continuum of care and services to people living with HIV disease. This article
      presents the results of a 2000-2001 survey of the 51 Title I Planning Councils.
      EMAs are serving significant numbers of females, with black and Hispanic persons
      constituting a majority of people served in 33 EMAs. Among the difficult to serve
      are substance abusers, people with chronic mental illness, multi-diagnosed
      people, the homeless, black males who have sex with males, and Hispanic persons.

PMID- 12500477
TI  - Access to care among disabled adults on Medicaid.
AB  - Although disabled individuals account for a disproportionate share of Medicaid
      expenditures, little is known about their health care needs and experiences. This
      article explores differences in access and use among key disability subgroups-
      adults with physical disabilities, mental illness, and mental
      retardation/development disabilities (MR/DD). We find that disabled Medicaid
      beneficiaries with mental illness and those with greater health and functional
      limitations face more difficulties in obtaining care. This suggests a need for
      changes in the system of care under Medicaid, including targeting efforts to
      improve access to individuals with specific types of disabilities.

PMID- 12500478
TI  - Future financial viability of rural hospitals.
AB  - Policymakers are concerned that some rural hospitals have suffered significant
      losses under the Balanced Budget Act (BBA) of 1997 and that access to inpatient
      and emergency care may be at risk. This article projects that the median total
      profit margin for rural hospitals will fall from 4 percent in 1997 to between 2.5
      and 3.7 percent after the BBA, Balanced Budget Refinement Act (BBRA) of 1999, and
      Benefits Improvement and Protection Act (BIPA) of 2000 are fully implemented in
      2004. The Critical Access Hospital (CAH) Program is expected to prevent
      reductions in inpatient and outpatient prospective payments from causing an
      increase in rural hospital closures.

PMID- 12500479
TI  - Screening for osteoporosis and colon cancer under Medicare.

PMID- 12500480
TI  - The new world disorder.

PMID- 12500481
TI  - The Royal Hospital Haslar and Ministry of Defence Hospital Unit Portsmouth 2002.

PMID- 12500482
TI  - Pityocampal erucism in a British serviceman in Croatia--a case report.
AB  - We present a case of erucism (caterpillar dermatitis) in a British serviceman
      deployed in Croatia on Operation Resolute. The aetiology, clinical features and
      diagnosis of erucism are discussed. Erucism should be highlighted as an
      environmental hazard in future troop deployments to the Mediterranean area.

PMID- 12500483
TI  - Surgical repair of intercostal pulmonary hernia secondary to cough induced rib
      fracture.
AB  - Intercostal pulmonary hernia, a protrusion of lung parenchyma with overlying
      pleural membranes through an abnormal defect in the thoracic cage, is an uncommon
      phenomenon. Rib fractures caused by coughing similarly represent an infrequently
      occurring clinical presentation. Pulmonary herniation through an intercostal
      defect caused by cough fractures has been described twice in the literature to
      our knowledge. We present a case of pulmonary herniation secondary to cough
      fracture in a chronic bronchitic, successfully treated by thoracotomy with
      application of the basic principles of hernia repair, and a discussion of the
      mechanisms of injury.

PMID- 12500484
TI  - First experiences of prescribing nicotine replacement therapy as part of a
      smoking cessation service on an SSBN patrol.

PMID- 12500485
TI  - The use of local anaesthesia in peripheral venous cannulation: current practice
      of junior doctors.
AB  - OBJECTIVE: To determine the rate of use of local anaesthetic in peripheral venous
      cannulation by pre-registration house officers and to determine reasons why they
      do not use it. DESIGN: Analysis of anonymous questionnaires distributed to pre
      registration house officers at scheduled weekly education meetings. SETTING: One
      regional hospital and three district general hospitals in the United Kingdom.
      RESULTS: 71 questionnaires were distributed directly to respondents and
      subsequently analysed. 46 respondents (65%) stated that they never used local
      anaesthetic for peripheral venous cannulation. Of those who used local
      anaesthetic the average rate of use was 6%. Of those who used local anaesthetic
      48% stated they used EMLA and 84% stated they used lignocaine. 4% stated they
      would use local anaesthetic for 22 gauge cannulae, 8% would use it for 20 gauge,
      24% for 18 gauge and 40% for 16 gauge and 28% for 14 gauge cannulae. 45% stated
      that using local anaesthetic was too time consuming, 35% stated it was not
      indicated, 21% stated that it made cannulation difficult, 13% stated that local
      anaesthetic was not available on the ward, 13% stated that it was logistically
      difficult, 4% stated that there was peer pressure not to use it, 4% stated they
      were not allowed to use local anaesthetic and 3% stated that it was practically
      difficult. 20% of respondents gave no reason. CONCLUSIONS: Despite good clinical
      evidence that the pain of peripheral venous cannulation can be successfully
      obviated using local anaesthetic, the rate of use by pre-registration house
      officers is low. It is suggested that during formal cannulation training, more
      emphasis be placed on the provision of analgesia. This should aim to increase the
      quality of care to those patients requiring intravenous cannulation as well as
      offering other potential benefits to doctors.

PMID- 12500486
TI  - "It's good to talk"--an audit of the communication of post-operative
      thromboembolic complications.
AB  - The risk of venous thromboembolism after surgery, with its associated morbidity
      and mortality, is an important component of obtaining informed consent for a
      surgical procedure. This risk of thromboembolic complications extends beyond the
      post-operative hospital stay; patients suffering such complications after
      discharge are generally not re-admitted under the care of the operating surgeon.
      A retrospective opening loop audit was undertaken to investigate the
      communication of post-operative thromboembolic complications between specialties
      in a large district general hospital. The operating surgeon was unaware of 87% of
      cases of pulmonary embolism and 20% of cases of deep vein thrombosis affecting
      patients in their post-operative period. The inter-specialty communication of
      post-operative complications is important to maintain a high standard of patient
      care and allow surgeons to make informed decisions about clinical practice.

PMID- 12500487
TI  - Surgeon Niel (sic) Smith Royal Navy 1780-1819.

PMID- 12500488
TI  - Good research and publication practice in biomedical science.

PMID- 12500489
TI  - Neurophysiological mechanisms of induction of meditation: a hypothetico-deductive
      approach.
AB  - A detailed analysis of methods of induction of meditation and meditative
      experience encountered therein implicates involvement of several mechanisms in
      inducing 'meditative effect'. 'Efferent attenuation', 'sensory attenuation' and
      'cognitive restructuring' appear three possible mechanisms employed in varying
      degree of combinations to produce the 'meditative effect' during different types
      of meditations. Using hypothetico-deductive approach, it is possible to generate
      a neural model for explaining the 'meditative effect'. Primarily, the meditation
      is produced by disengaged association cortices driven by thalamus or other older
      group of reticular nuclei. Secondarily, there may be involvement of some more
      phylogenetically older structures depending upon depth and types of meditation.
      This model explains induction, maintenance and long-term effects of meditation.

PMID- 12500490
TI  - Serum copper levels in carcinoma of ovary and cervix.
AB  - The role of serum copper level (SCL) as a diagnostic and prognostic tool in
      genital tract malignancies was evaluated. SCL was employed as a marker for
      response to treatment (surgical/radiotherapy). 129 women attending gynaecology
      outpatient department or admitted in the gynecology ward were studied. Of these
      77 patients in the disease (study) group were proven cases of genital tract
      malignancies and 52 served as controls. Outcome measures studied were: SCL levels
      estimated before initiation of any treatment i.e. surgery/radiotherapy;
      thereafter, at two weeks after completion of treatment. Follow up of the study
      subjects was done between 4-8 weeks and 8-10 weeks, when the patients were
      evaluated for any recurrence of disease and SCLs were also estimated. Kruskal
      Wallis one-way analysis of variance determined whether values varied
      significantly among the different groups studied. Mean SCLs were found to be
      significantly elevated in cases of Ca ovary (n = 15), early CaCx (n = 14) and
      late CaCx (n = 48), as compared to the control group, comprising of women with no
      signs and symptoms of malignancy (n = 52). SCLs decreases significantly (P <
      0.001) after treatment of Ca ovary and CaCx. These results indicate a possible
      clinical usefulness of estimating serum copper levels in women with genital tract
      cancer and suggest a role for SCL in the evaluation of the disease activity and
      as a prognostic tool in the management of genital malignancies.

PMID- 12500491
TI  - Evaluation of hepatoprotective activity of Ginkgo biloba in rats.
AB  - The mechanism of hepatoprotective effects of Ginkgo biloba (GB), an herbal
      preparation with wide variety of therapeutic application, on paracetamol (Pcml)
      induced hepatic damage in rats has been investigated. GB treatment restored the
      marker enzyme levels indicating the in vivo protective effects against Pcml
      induced liver damage both in preventive and curative aspects. GB also reversed
      the increased TBARS levels, and elevated the GSH content of the liver. The
      results obtained from the study indicate hepatoprotective nature of GB, which
      might be due to its ability to prevent lipid peroxidation and replenishing the
      gllutathione level. The effects of GB were comparable to that of silymarin.

PMID- 12500492
TI  - A study of extra genital effects of estrogen and progesterone.
AB  - Although some extragenital effects (EGEs) of the female sex steroids (FSS) have
      been known for fairly long time, serious research on it has been taken up only in
      recent time. This paper has tried to explore the EGEs of Estrogen (E) and
      Progesterone (P). This study was based on human beings as experimental subjects.
      In this clinical study, three further subdivisions were made: (i) Patients of
      dysfunctional uterine bleeding (DUB) who were therapeutically advised to use
      orally ingestible synthetic P tablets. These subjects were studied for any P
      induced changes in the psychoanalytical score, EEG, lung function tests (LUFTs),
      ECG; their blood Female sex steroid levels were also measured. (ii) Another group
      of women suffering from perimenopausal syndrome were given synthetic E tablets
      and the E induced changes (if any) of the same above mentioned parameters were
      studied. (iii) A third group consisting of healthy women were given oral
      contraceptive pills (OCP) containing both E and P and the above mentioned
      parameters were studied to see whether the OCP could cause any change. The
      results have been discussed. Attempts have been made to see whether our findings
      give any hint of any mode of action of the FSS studied and so forth.

PMID- 12500493
TI  - Assessment of olfactory status in allergic and non-allergic rhinitis patients.
AB  - A study undertaken to assess the olfactory acuity in allergic (group I) and non
      allergic rhinitis (group II) patients in comparison with age and sex matched
      controls (group III). Patients presenting with atleast three of the five cardinal
      symptoms of rhinitis i.e. rhinorrhoea, sneezing, itching, headache and nasal
      obstruction were grouped as non-infective rhinitis and further divided into
      allergic rhinitis (group I, n = 20) and non-allergic rhinitis (group II, n = 20)
      based on nasal smear cytology positivity or negativity for eosinophils
      respectively. Detailed Ear, Nose and Throat examination was carried out in both
      the groups and peripheral blood samples were analysed for total, differential
      leukocyte and absolute eosinophil counts using standard techniques. In all the
      three groups the olfactory thresholds for 5 odorants i.e. musk (M), formalin (F),
      camphor (C), asafoetida (A, 10% aqueous solution) and oil of peppermint (P, 20%)
      were evaluated for testing musky, pungent, camphorous, putrid and minty odours
      respectively by the method described by Elsberg and Levy for quantitative
      olfactometry. The results indicated elevation of olfactory thresholds (delta %,
      calculated taking control values as 100%) for 4 or 5 odorants in group I and
      group II patients respectively as compared with controls (group I: delta % for P-
      89.6%; M--116.4%; A--55.8%; P < 0.001; C--73.1%; P < 0.02; F--26.6% N.S.; group
      II: P--96.9%; M--99.3%, P < 0.01 for both; A--66.8%; C--102.7%, P < 0.001; F-
      42%, P < 0.05). In the non allergic rhinitis group the magnitude of the olfactory
      loss was more severe except for the odorant musk. Further interpretations as per
      gender based specificities revealed more severe olfactory loss in males of both
      the groups for the odorants peppermint and musk and moderately severe olfactory
      loss for formalin and camphor as compared to females. However, for the odorant
      asafoetida females showed greater olfactory loss than males in both the groups
      (delta % 73.38% versus 52% in group I and 81.29% versus 69.7% in group II).

PMID- 12500494
TI  - The effect of thymoquinone on blood lipids in rats.
AB  - We have studied the effect of thymoquinone on the blood levels of cholesterol,
      triglycerides, HDL and LDL in albino rats. A total of 200 rats, 150 test group
      and 50 as controls, were included in the study. Six doses of thymoquinone (0.5,
      1, 2, 4, 6, and 8 mg/kg/day) were given through intraperitonial injections at 8
      Am. The drug was administered for 5 durations 1, 4, 7, 10, and 14 days.
      Thymoquinone produced significant reduction in the blood level of all parameters
      studied. There was no linear dose or time dependent effect on these parameters.
      The effect of thymoquinone started after 4 days with all doses and continued,
      with some swings, in the rest of the duration. The dose of 8 mg/kg was found to
      be toxic. It is concluded that thymoquinone has a hypocholestrolemic as well as a
      reducing effect on triglycrides, HDL and LDL. Therefore, we recommend further
      research on the therapeutic effect of thymoquinone in related diseases in humans
      and animals.

PMID- 12500495
TI  - Evaluation of the analgesic effect of neurosteroids and their possible mechanism
      of action.
AB  - The present study investigates the effect of progesterone (P), a pregnane
      precursor of neurosteroids and 4-chlordiazepam (4-CD), a high affinity ligand for
      mitochondrial diazepam binding inhibitor receptor (MDR) that stimulates
      neurosteroid synthesis, in both acute, (tail flick latency test, TFL) and
      chronic, (formalin-induced pain response, FT), models. Both P and 4-CD showed an
      analgesic response in these models. The effect of P and 4-CD was antagonized by
      bicuculline on TEL but not in FT. However, naloxone attenuated the
      antinociceptive response of P and 4-CD in TFL as well as FT. Further, P and 4-CD
      pretreatment potentiated the analgesic effect of morphine and nimodipine in both
      the models of pain sensitivity. Thus, neurosteroids produce an antinociceptive
      effect which may be mediated by modulation of GABAergic and/or opiodergic
      mechanisms as well as voltage gated calcium channels.

PMID- 12500496
TI  - Biodegradable microspheres of curcumin for treatment of inflammation.
AB  - Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7) was
      formulated as prolonged release biodegradable microspheres for treatment of
      inflammation. Natural biodegradable polymers, namely, bovine serum albumin and
      chitosan were used to encapsulate curcumin to form a depot forming drug delivery
      system. Microspheres were prepared by emulsion-solvent evaporation method coupled
      with chemical cross-linking of the natural polymers. Curcumin could be
      encapsulated into the biodegradable carriers upto an extent of 79.49 and 39.66%
      respectively with albumin and chitosan. Different drug:polymer ratios did not
      affect the mean particle size or particle size distribution significantly.
      However, the concentration of the crosslinking agent had remarkable influence on
      the drug release. In-vitro release studies indicated a biphasic drug release
      pattern, characterized by a typical burst-effect followed by a slow release which
      continued for several days. Evaluation of antinflammatory activity using Freund's
      adjuvant induced arthritic model in Wistar rats revealed significant difference
      between both the formulations, albumin microspheres and chitosan micropheres as
      well as against control. It was evident from the present study that the curcumin
      biodegradable microspheres could be successfully employed as prolonged release
      drug delivery system for better therapeutic management of inflammation as
      compared to oral or subcutaneous route.

PMID- 12500497
TI  - Effect of long-term dehydration on serum constituents in extreme climatic
      conditions in camel (Camelus dromedarius).
AB  - Eight healthy female adult camels were used to study the effect of long term
      dehydration on serum constituents in extreme climatic conditions viz. cold and
      hot. The dehydration phases were of 24 days in cold and 13 days in hot
      conditions. The changes in sodium, potassium, calcium and phosphorus were non
      significant (P > 0.05) while in chloride, glucose, total proteins, urea,
      bilirubin, cholesterol and creatinine were significant (P < or = 0.05) during
      dehydration phase. The mean values of all the constituents tended to return to
      normal as the rehydration phase advanced. Changes in sodium and potassium in
      dehydrated camels reflected that they were able to maintain the salt balance.

PMID- 12500498
TI  - Antioxidant effect of Coscinium fenestratum in carbon tetrachloride treated rats.
AB  - Antioxidant effect of methanol extract of Coscinium fenestratum stem powder was
      examined using carbon tetrachloride-intoxicated rat liver as the experimental
      model. Hepatotoxic rats were treated with the methanol extract for 90 days
      (daily, orally at the dose of 60 mg/kg body weight). Lipid peroxidation in carbon
      tetrachloride-administered rats was evidenced by a marked elevation in the levels
      of thiobarbituric acid reactive substances and diene conjugates, and also a
      profound diminution in glutathione content in the liver. Rats co-administered
      with the methanol extract retained an almost normal level of these constituents.
      The decreased activities of antioxidant enzymes, such as superoxide dismutase,
      catalase, glutathione peroxidase and glutathione reductase in carbon
      tetrachloride-intoxicated rats, and its retrieval towards near-normalcy in the
      methanol extract co-administered animals revealed the effectiveness of Coscinium
      fenestratum in combating oxidative stress due to hepatic damage. The findings
      provide a rationale for further studies on isolation of active principles and its
      pharmacological evaluation.

PMID- 12500499
TI  - Effect of melatonin and beta-carotene on indomethacin induced gastric mucosal
      injury.
AB  - The study was conducted to examine the role of free radicals in Indomethacin
      induced gastric mucosal injury and to evaluate the gastroprotective effects of
      melatonin and beta-carotene. Gastric mucosal injury was produced in rats by
      administering indomethacin 30 mg/kg subcutaneously. Melatonin was administered in
      three different doses of 5, 10 and 20 mg/kg, 30 minutes prior to the
      administration of indomethacin. Beta-carotene was administered as a single dose
      of 100 mg/kg. Following parameters were calculated: ulcer index, lipid
      peroxidation and antioxidant defense enzymes i.e. superoxide dismutase,
      glutathione peroxidase and catalase. Indomethacin caused gastric mucosal injury
      in the form of haemorrhages, increased the lipid peroxidation and decreased the
      levels of the antioxidant defense enzymes. Melatonin (20 mg/kg) and beta-carotene
      decreased the ulcer index and lipid peroxidation, and reduced the decrease in
      antioxidant enzyme levels. These findings suggest the melatonin and beta-carotene
      show protective effect against indomethacin induced gastric injury and this
      effect is mediated by scavenging of oxygen derived free radicals.

PMID- 12500500
TI  - Evaluation of analgesic, antipyretic and anti-inflammatory activity of
      spirobarbitunylphenothiazines in rodents.
AB  - Analgesic, antipyretic and anti-inflammatory activities of newly synthesized
      spirobarbitunylphenothiazines viz 10-[7, 11-Di(4-4' dimethoxphenyl)-3-oxo-9
      methylaminoimino-2, 4-diazaspiro [5.5] undecane 1, 5 dione] acetylphenothiazine
      (test drug A) and 10-[7, 11-Di (N.N-dimethylaminophenyl)-3-oxo-9-methylaminoimino
      2, 4-diazaspiro [5, 5] undecane-1, 5 dione] acetylphenothiazine (test drug B)
      have been screened in Swiss mice and Wistar rats. The peripheral analgesic
      activity of test drugs A and B was investigated by acetic acid induced writhing
      test in Swiss mice while the central analgesic action was assessed by hot-wire
      (tail flick test) of the analgesiometer and tail-clip test in Wistar rats.
      Antipyretic activity was assessed on Brewer's yeast induced pyrexic model while
      antiinflammatory activity was seen on carrageenan induced hind paw oedema.
      Analgesic activity was found to be only of peripheral type as there was reduction
      of 66% in writhing responses by test drugs A and B in dose of 80 mg/kg in mice.
      No change in the tail flick responses was observed on analgesiometer or by tail
      clip by both the test drugs. Reduction of 1.5 to 2.0 degrees C in rectal
      temperature was observed in pyretic rats by test drugs A and B in dose of 80
      mg/kg. 80% reduction in paw volume was noted in 80 mg/kg dose of both the test
      drugs which was comparable to the anti-inflammatory activity of 300 mg/kg, p.o.
      of phenylbutazone.

PMID- 12500501
TI  - A study of cardiovascular effects of Azadirachta indica (neem) on isolated
      perfused heart preparations.
AB  - The effects of aqueous leaf extract of Azadirachta indica were evaluated on
      isolated prefused frog and rabbit heart. Dose dependent negative inotropic and
      chronotropic effects were observed in both the heart preparation. An increase in
      coronary blood flow in isolated rabbit heart was observed. The effects were not
      blocked by atropine and mepyramine in both the preparations. The data suggests
      that A. indica could be of benefit in coronary artery disease and arrhythmias.

PMID- 12500502
TI  - Serum profile of calcium, phosphorus and magnesium in crossbred heifers as
      influenced by gestation and early lactation.
AB  - The serum profile of certain macroelements such as calcium, inorganic phosphorus
      and magnesium of healthy crossbred heifers in Kerala were estimated before and
      after conception, at different stages of pregnancy and early lactation. The serum
      concentration of calcium showed a decreasing trend during second trimester of
      pregnancy which attained significantly lower (P < 0.01) value (5.57 mg/dl) when
      compared to controls. By the ninth month of pregnancy calcium level was elevated.
      The serum phosphorus level was significantly higher (P < 0.01) during the fifth
      month of pregnancy (8.29 mg/dl) when compared to controls and then it was
      decreased by the 9th month of pregnancy. The serum magnesium level showed an
      increasing tendency to attain a peak value (2.55 mg/dl) by the 9th month of
      pregnancy which was significantly higher (P < 0.01) when compared to the control.
      During the period of study no production diseases were encountered in the animals
      screened which indicated that the serum calcium, phosphorus and magnesium profile
      of these animals were at the optimum level.

PMID- 12500503
TI  - Nifedipine potentiates gabapentin antinociception in rats.
AB  - To evaluate the involvement of Ca++ channels in Gabapentin antinociception. In
      healthy male albino rats formalin (50 microliters, 5%) was injected at the
      planter surface of the paw. Pain score was calculated. Antinociceptive effect of
      (10, 30 mg/kg) gabapentin and (3, 10 mg/kg) nifedipine alone and on co
      administration of sub analgesic doses was studied 30 minutes after formalin
      injection and reduction in pain scores was calculated. Gabapentin (30 mg/kg) and
      nifedipine (10 mg/kg) reduced the pain score in formalin injected rats.
      Gabapentin (10 mg/kg) and nifedipine (3 mg/kg) given alone did not modify pain
      score, however, on co-administration they significantly reduced the pain score.
      Study provides evidence of involvement of Ca++ channels in gabapentin
      antinociception.

PMID- 12500504
TI  - Biliary stones and ascariasis--our experience.

PMID- 12500505
TI  - Effect of ursodeoxycholic acid on free radical mediated DNA damage--an in vitro
      study.

PMID- 12500506
TI  - The age of arthritis.

PMID- 12500507
TI  - Fish oil and toenails.

PMID- 12500508
TI  - Intravenous induction agents: opioids.

PMID- 12500510
TI  - The impact of intraoperative transoesophageal echocardiography on an unselected
      cardiac surgical population: a review of 2343 cases.
AB  - Although intraoperative transoesophageal echocardiography (TOE) has an
      established role in the management of some cardiac surgical procedures, there is
      little data on its impact on coronary artery bypass graft (CABG) cases that are
      stratified for clinical risk. This is a retrospective review of the surgical
      impact of intraoperative TOE on 2,343 unselected cardiac cases. The surgical
      impact of TOE findings were rated E (essential)--resulted in changes to the
      proposed surgical procedure or V (valuable)--the surgical technique for the
      planned surgery was altered. The surgical impact that routine TOE had on low-,
      medium- and high-risk CABG cases was also examined. The surgical impact of TOE
      for the total study population (E + V) was 4.5%. The impact was greatest in
      combined CABG + mitral valve procedures (18%). The impact in CABG cases was 3.5%
      overall, with an estimated impact in low-risk patients of 2.8% (95% CI. 2.7-3.0%)
      versus 6.7% (95% CI. 5.9-7.7%) in high-risk cases. The commonest E-impact in CABG
      patients was unscheduled valve surgery (2.6% of high-risk patients). The
      complication rate attributable to TOE was 0.09%. These findings provide indirect
      evidence for a potential patient benefit from the routine use of TOE in cardiac
      surgery.

PMID- 12500509
TI  - The cerebrovascular effects of adrenaline, noradrenaline and dopamine infusions
      under propofol and isoflurane anaesthesia in sheep.
AB  - Infusions of catecholamines are frequently administered to patients receiving
      propofol or isoflurane anaesthesia. Interactions between these drugs may affect
      regional circulations, such as the brain. The aim of this animal (sheep) study
      was to determine the effects of ramped infusions of adrenaline, noradrenaline
      (10, 20, 40 micrograms/min) and dopamine (10, 20, 40 micrograms/kg/min) on
      cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular
      resistance (CVR) and cerebral metabolic rate for oxygen (CMRO2). These
      measurements were made under awake physiological conditions, and during
      continuous propofol (15 mg/min) or 2% isoflurane anaesthesia. All three
      catecholamines significantly and equivalently increased mean arterial pressure
      from baseline in a dose-dependent manner in the three cohorts (P < 0.001). In the
      awake cohort (n = 8), dopamine (P < 0.01) significantly increased CBF from
      baseline whilst adrenaline and noradrenaline did not (P > 0.05). Under propofol
      (n = 6) and isoflurane (n = 6), all three catecholamines significantly increased
      CBF (P < 0.001). Dopamine caused the greatest increase in CBF, and was associated
      with significant increases in ICP (awake: P < 0.001; propofol P < 0.05;
      isoflurane P < 0.001) and CVR (isoflurane P < 0.05). No significant changes in
      CMRO2 were demonstrated. Under propofol and isoflurane anaesthesia, the
      cerebrovascular effects of catecholamines were significantly different from the
      awake, physiological state, with dopamine demonstrating the most pronounced
      effects, particularly under propofol. Dopamine-induced hyperaemia was associated
      with other cerebrovascular changes. In the presence of an equivalent effect on
      mean arterial pressure, the exaggerated cerebrovascular effects under anaesthesia
      appear to be centrally mediated, possibly induced by propofol- or isoflurane
      dependent changes in blood-brain barrier permeability, thereby causing a direct
      influence on the cerebral vasculature.

PMID- 12500511
TI  - The effects of intravenous lignocaine on haemodynamics and seizure duration
      during electroconvulsive therapy.
AB  - Electroconvulsive therapy (ECT) is commonly associated with acute hyperdynamic
      cardiovascular responses, and we hypothesize that intravenous lignocaine can
      blunt this response. We have measured the effect of lignocaine 1.5 mg/kg i.v. on
      heart rate and mean arterial pressure during electroconvulsive therapy.
      Furthermore, we also assessed seizure duration using both the cuff method and two
      lead electroencephalography. We studied 25 patients using a randomized, double
      blind, placebo-controlled crossover study design. Patients in the control group
      were given intravenous saline 0.075 ml/kg, and those in the lignocaine group were
      given intravenous lignocaine 2% 1.5 mg/kg, and this treatment was conducted one
      minute before intravenous propofol 1.5 mg/kg to induce unconsciousness.
      Succinylcholine 1.5 mg/kg was then administered intravenously and electrical
      stimulation was administered after fasciculation. Measurements were taken at the
      baseline, prior to succinycholine, prior to electroconvulsive therapy and at the
      peak response after electroconvulsive therapy. Intravenous lignocaine
      significantly reduced the increases in heart rate after electroconvulsive
      therapy, as compared with the placebo. The use of intravenous lignocaine was,
      however, associated with a remarkably shortened seizure duration. Due to the
      reduction in seizure duration, routine administration of intravenous lignocaine
      may not be advisable since it may interfere with the psychotherapeutic efficacy
      of electroconvulsive therapy. However, intravenous lignocaine medication for
      electroconvulsive therapy is potentially useful for reducing tachycardia in high
      risk patients and reducing the severity of propofol injection pain in comparison
      with a placebo.

PMID- 12500512
TI  - Reliability of procalcitonin as a severity marker in critically ill patients with
      inflammatory response.
AB  - Procalcitonin (PCT) is increasingly recognised as an important diagnostic
      parameter in clinical evaluation of the critically ill. This prospective study
      was designed to investigate PCT as a diagnostic marker of infection in critically
      ill patients with sepsis. Eighty-five adult ICU patients were studied. Four
      groups were defined on the basis of clinical, laboratory and bacteriologic
      findings as systemic inflammatory response syndrome (SIRS) (n = 10), sepsis (n =
      16), severe sepsis (n = 18) and septic shock (n = 41). Data were collected
      including C-reactive protein (CRP), PCT levels and Sequential Organ Failure
      Assessment and Acute Physiology and Chronic Health Evaluation II scores on each
      ICU day. PCT levels were significantly higher in patients with severe sepsis and
      septic shock (19.25 +/- 43.08 and 37.15 +/- 61.39 ng/ml) than patients with SIRS
      (0.73 +/- 1.37 ng/ml) (P < 0.05 for each comparison). As compared with SIRS
      patients, plasma PCT levels were significantly higher in infected patients (21.9
      +/- 47.8 ng/ml), regardless of the degree of sepsis (P < 0.001). PCT showed a
      higher sensitivity (73% versus 35%) and specificity (83% versus 42%) compared to
      CRP in identifying infection as a cause of the inflammatory response. Best cut
      off levels were 1.31 ng/ml for PCT and 13.9 mg/dl for CRP. We suggest that PCT is
      a more reliable marker than CRP in defining infection as a cause of systemic
      inflammatory response.

PMID- 12500513
TI  - The influence of methylene blue infusion on cytokine levels during severe sepsis.
AB  - The aim of our study was to assess the effect of methylene blue infusion on
      plasma levels of cytokines in severe sepsis. In a prospective, randomized, double
      blind, placebo-controlled study, patients received either methylene blue 0.5
      mg.kg-1.h-1 (MB group, n = 15) or similar volume of isotonic saline (control
      group, n = 15) i.v. for 6 hours. Plasma concentrations of tumour necrosis factor
      alpha, interleukin-1, interleukin-2 receptor, interleukin-6, interleukin-8 were
      measured by sensitive immunoassays at basal (15 min before start of the study),
      immediately after, and at 24 and 48 hours after methylene blue infusion. We
      evaluated haemodynamic parameters (mean arterial pressure, heart rate), blood
      gases, methaemoglobin levels, and biochemical parameters at the same time.
      Methylene blue administration had no significant effect on plasma cytokine
      levels, blood gases and biochemical parameters. When compared to placebo infusion
      in controls, methylene blue administration resulted in significantly higher mean
      arterial pressure (85 +/- 14 mmHg vs 74.1 +/- 10.3 mmHg; P < 0.01), and
      methaemoglobin levels (1.06 +/- 0.22% vs 0.9 +/- 0.05%; P < 0.05). Furthermore,
      comparison with baseline levels revealed significantly increased both mean
      arterial pressure (85 +/- 14 mmHg and 74.1 +/- 10.2 mmHg; P < 0.05) and
      methaemoglobin levels (1.06 +/- 0.22% and 0.88 +/- 0.06%; P < 0.05) in MB group.
      There was no difference in mortality rates between the groups. We found that
      methylene blue infusion did not change cytokine levels or outcome in severe
      sepsis. The administration of methylene blue, however, resulted in a transient
      increase in arterial pressure. Because of the limited size of the present study,
      and the short period of observation, our findings need to be confirmed by larger
      clinical trials of methylene blue infused in a dose-titrated manner.

PMID- 12500514
TI  - Ratio of patient's height to thyromental distance improves prediction of
      difficult laryngoscopy.
AB  - Several tests have been proposed to predict difficult laryngoscopy or intubation.
      The thyromental distance (TMD) is often used for these purposes but this
      measurement, used alone, is unreliable. This study tested the hypothesis that the
      ratio of the patient's height to TMD (ratio of height to TMD = RHTMD) would
      improve the accuracy of predicting difficult laryngoscopy compared with TMD
      alone. Two hundred and seventy patients were evaluated preoperatively using the
      TMD and RHTMD. The two tests were compared analyzing the area under the receiver
      operating characteristic curves (AUC). Difficult laryngoscopy occurred in 16
      patients (5.9%). The AUC of RHTMD was significantly greater (P < 0.007) when
      compared to TMD, indicating a more accurate prediction by the RHTMD. A ratio of
      25 for the RHTMD was found to be the optimal cut-off value to predict difficult
      laryngoscopy. When the sensitivity of both tests was 0.81, the RHTMD had a
      significantly greater specificity (0.91) than the TMD (0.73). Based on our
      results, we recommend that the RHTMD should be used instead of the TMD.

PMID- 12500515
TI  - Reflex responses to insertion of the intubating laryngeal mask airway, intubation
      and removal of the ILMA.
AB  - We studied 21 patients (ASA 1 or 2) to investigate the skin vasomotor reflex
      (SVmR) and haemodynamic responses to insertion of an intubating laryngeal mask
      airway (ILMA), tracheal intubation using the ILMA and removal of the ILMA.
      Anaesthesia was induced with fentanyl, midazolam, vecuronium and nitrous oxide. A
      size 4 ILMA was inserted using the standard technique, and a silicone reinforced
      tracheal tube (7.5 mm, ID) was passed through it. After confirming successful
      intubation, the ILMA was removed using the stabilizing rod. The three procedures
      were performed at approximately one-minute intervals. Insertion of the ILMA,
      intubation and removal of the ILMA all significantly reduced the skin blood flow
      on the ring finger in all patients. The mean amplitudes of the SVmR were 0.46 (SD
      0.29), 0.54 (0.32) and 0.68 (0.21) respectively. The magnitude of the SVmR and
      the haemodynamic changes induced by removal of the ILMA were significantly larger
      than those accompanying the other two procedures. Use of the ILMA for intubation
      and removal of the ILMA produces three stimuli and the removal of the ILMA
      produces the greatest response.

PMID- 12500516
TI  - Appropriate size of laryngeal mask airway for children.
AB  - The aim of this crossover study was to determine the optimal size of laryngeal
      mask airway in children weighing 10 to 20 kg. In each of 67 apnoeic anaesthetized
      children, the size 2 and size 2 1/2 laryngeal mask airways were inserted
      consecutively by a skilled user and the cuff inflated to 60 cmH2O. Each LMA was
      assessed for the ease of insertion (by the number of attempts), oropharyngeal
      leak pressure, anatomical position (assessed fibreoptically) and the volume of
      air required to achieve intracuff pressure of 60 cmH2O. During the measurement of
      oropharyngeal leak pressure, the airway pressure was not allowed to exceed 30
      cmH2O. There was no failed attempt at insertion with any size. The oropharyngeal
      leak pressure was significantly less for the size 2 LMA compared to the size 2
      1/2 LMA (P < 0.001). The oesophagus was visible on three occasions, all with the
      size 2 LMA. Gastric insufflation occurred in three patients, all with the size 2
      LMA. The incidence of low oropharyngeal leak pressure (< 10 cmH2O) was low (9.0%)
      and all occurred with the size 2 LMA. The fibreoptic bronchoscope scores were not
      significantly different between the two sizes of LMAs. The volume of air to
      achieve intracuff pressure of 60 cmH2O was much lower than the maximum
      recommended volume (5.1 ml for size 2 and 6.2 ml for size 2 1/2). We conclude
      that the size 2 1/2 LMA provides a better fit than size 2 in children 10 to 20
      kg.

PMID- 12500517
TI  - An autologous blood donation program for paediatric scoliosis patients in Hong
      Kong.
AB  - A retrospective audit was conducted to determine the safety, efficacy and patient
      satisfaction related to a preoperative autologous blood donation program for
      children and teenagers undergoing corrective surgery for scoliosis. Forty-five of
      the 77 patients donated the requested amount of blood. These 45 compliant
      patients had been requested to donate fewer units of blood than noncompliant
      patients (mean 4.0 vs 4.6 respectively, P = 0.02). Twelve patients required
      allogeneic blood transfusion. Two patients had surgery delayed making the
      collected autologous blood unavailable. The extent of the operation was
      associated with the need for allogeneic blood transfusion. Six and a half percent
      of all donated units of blood were discarded. No major complications were
      reported. Overall, 93% of patients were satisfied with the program. With careful
      patient selection, good inter-departmental coordination and teamwork,
      preoperative autologous blood donation in paediatric patients undergoing
      extensive corrective surgery for scoliosis is safe and effective.

PMID- 12500518
TI  - Transient lumbar pain after 5% hyperbaric lignocaine spinal anaesthesia in
      patients having minor vascular surgery.
AB  - Transient lumbar pain has been reported to occur frequently in patients having
      surgery using 5% hyperbaric lignocaine for spinal anaesthesia. The incidence of
      transient lumbar pain is highest with this agent in patients having surgery in
      the lithotomy position and in outpatients. The aim of this audit was to determine
      the incidence of transient lumbar pain in patients having minor surgery for the
      complications of peripheral vascular disease, a group of patients in whom short
      duration spinal anaesthesia is desirable. One hundred patients were audited
      prospectively. All patients had 5% hyperbaric lignocaine spinal anaesthesia and
      were followed up postoperatively utilizing a standardized questionnaire to
      determine the incidence of transient lumbar pain. The condition was found to
      occur in 4% of patients. This low incidence of transient lumbar pain justifies
      the continued use of 5% hyperbaric lignocaine for spinal anaesthesia in this
      group of patients.

PMID- 12500519
TI  - Use of propofol infusion in Australian and New Zealand paediatric intensive care
      units.
AB  - Despite the risk of propofol infusion syndrome, a rare but often fatal
      complication of propofol infusion in ventilated children and possibly adults,
      propofol infusion remains in use in paediatric intensive care units (PICU). This
      questionnaire study surveys the current pattern of use of this sedative infusion
      in Australian and New Zealand PICUs. Thirty-three of the 45 paediatric intensive
      care physicians surveyed (73%), from 12 of the 13 intensive care units, returned
      completed questionnaires. The majority of practitioners (82%) use propofol
      infusion in children in PICU, the main indication being for short-term sedation
      in children requiring procedures. 39% of respondents consider propofol infusion
      useful in ventilated children requiring longer-term sedation. 67% of paediatric
      intensivists use maximum infusion doses that may be considered dangerously high
      (> or = 10 mg/kg/h). Nineteen per cent use propofol infusion for prolonged
      periods (> 72 hours). A smaller proportion (15%) of respondents indicate that
      they may use both higher doses and prolonged periods of infusion, a practice
      likely to lead to a greater chance of serious adverse events. Knowledge of local
      protocols for the use of propofol infusion is associated with a significantly
      greater level of monitoring for possible adverse events. We suggest that national
      guidelines for the use of propofol infusion in children should be developed.
      These should include clear indications and contraindications to its use, a
      maximum dose rate and maximum period of infusion, with a ceiling placed on the
      cumulative dose given and clearly stated minimum monitoring requirements.

PMID- 12500520
TI  - Factors affecting performance of air tonometry using the TONOCAP.
AB  - Saline tonometry has been replaced by automated air tonometry (TONOCAP). As with
      saline tonometry there are some pitfalls to consider. We investigated the
      influence of different filling handicaps to the tonometry catheter sampling
      balloon on measurement of regional PCO2 (PrCO2). In an in vitro set-up, PrCO2 was
      measured using the TONOCAP at intervals of 10 minutes from a 8F tonometry
      catheter sampling balloon placed in a container with constant PCO2 (PcCO2).
      Catheter alarms displayed by the TONOCAP device were noted. The following
      experiments were performed: A) control measurement without modifications; B)
      adding deadspace of 7 ml into the sampling line; C) placing the sampling balloon
      in a 3 ml syringe; D) cross-clamping of the sampling balloon. Each experiment was
      performed four times using two catheters on two TONOCAP devices. Differences
      between PcCO2 and PrCO2 were calculated as Pc-rCO2. Results are presented as mean
      +/- SD and were compared using ANOVA with Scheffe's correction. Pc-rCO2 in the
      control set-up (A) amounted to 0.16 +/- 0.22%. Increasing catheter deadspace (B)
      resulted in a higher Pc-rCO2 of 3.2 +/- 0.57% (P < 0.0001). Restriction of
      balloon expansion (C) caused an Pc-rCO2 gap of 1.17 +/- 0.36% (P < 0.0001). With
      filling restriction (D) the Pc-rCO2 gap increased to 3.87 +/- 0.29% (P < 0.0001).
      The catheter alarms provided were not able to indicate all catheter problems and
      initial alarms disappeared although the problems continued. We conclude that
      impaired catheter deadspace to balloon volume relation can negatively influence
      accuracy of PrCO2 measurement by the TONOCAP.

PMID- 12500521
TI  - The ULCO anaesthetic suitcase.
AB  - This paper describes the ULCO Portable Field Anaesthesia Machine, also known as
      the ULCO Anaesthetic Suitcase. The ULCO Anaesthetic Suitcase is a portable and
      versatile anaesthetic machine. It consists of flowmeters, back bar with two
      Penlon Oxford Miniature Vaporizers (OMV 50) and a common gas outlet mounted in
      the lid of a sturdy aluminium suitcase. A choice of drawover circuit, circle
      absorber system or a MultiCircuit System valve allows either drawover, circle or
      Mapleson A or D continuous flow (plenum) anaesthesia to be given in virtually any
      situation, oxygen supply permitting.

PMID- 12500522
TI  - Life-threatening pulmonary oedema secondary to tracheal compression.
AB  - We present a case of negative pressure pulmonary oedema due to an overlooked
      cause. A 45-year-old female patient presented to the emergency department
      unconscious with severe pulmonary oedema. Subsequent investigations revealed a
      thyroid goitre causing significant tracheal compression. This case report
      highlights an extremely rare but potentially dangerous sequela of upper airway
      obstruction.

PMID- 12500523
TI  - Deafness--a complication of nasopharyngeal airways.
AB  - We report a patient who developed temporary deafness secondary to oedema of the
      uvula and soft palate following prolonged continuous positive airway pressure via
      a nasopharyngeal airway.

PMID- 12500524
TI  - Induction of anaesthesia in the home.
AB  - An intellectually impaired adult with a history of escalating violence towards
      hospital personnel was given an anaesthetic in his home prior to transfer to
      hospital for surgery. We review the implications and problems encountered, and
      suggest means by which such a retrieval can occur smoothly.

PMID- 12500525
TI  - The LMA, elective tracheostomy and nasopharyngeal carcinoma.

PMID- 12500526
TI  - Minimally invasive preperitoneal inguinal hernia repair with epidural
      anaesthesia.

PMID- 12500527
TI  - Spinal 5% heavy lignocaine.

PMID- 12500528
TI  - Jewish patients in intensive care units.

PMID- 12500529
TI  - Awareness under TIVA.

PMID- 12500530
TI  - EEG monitoring improves quality and safety of TIVA.

PMID- 12500531
TI  - [Genome domains and domain regulatory elements].
AB  - Gene activity regulation at the level of genome domains is considered with
      special emphasis on locus control regions (LCR), which are thought to act as
      dominant regulatory elements providing for the active state of tissue-specific
      gene domains. Detailed analysis was made of experimental data on the organization
      and function of mammalian beta-globin gene LCR. On recent evidence, this LCR is
      necessary for high-level expression of the globin genes, but not for the active
      state of the domain. These data are compared with earlier findings suggesting a
      key role of LCR in the organization of active genome domains. The boundaries of
      functional genome domains are also considered.

PMID- 12500532
TI  - [Translational regulation in early development of eukaryotes].
AB  - Data on translational regulation of stored mRNAs in oocytes, embryos, and
      differentiated tissues are reviewed. Particular emphasis is placed on the role of
      untranslated mRNA regions, which bind with certain proteins involved in the
      function of individual mRNAs. Examples are given of the spatial and temporal
      translational regulation of several mRNAs in embryo development.

PMID- 12500534
TI  - [Polymorphism of the apolipoprotein E gene and the risk of myocardial
      infarction].
AB  - The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide
      substitutions in exon 4 was analyzed in Russian and Tatar patients with
      myocardial infarction (MI) from Bashkortostan. Alleles epsilon 2, epsilon 3, and
      epsilon 4 were identified by PCR. The genotype frequency distribution proved to
      be age-dependent in healthy Russians, genotype E2/3 increasing in frequency in
      subjects beyond 45. Russians who suffered MI under 45 had lower frequencies of
      genotype E3/3 (50.00% vs. 75.47% in controls of the same age, P = 0.013, OR =
      0.33) and allele epsilon 3 (72.12% vs. 85.85%, P = 0.020, OR = 0.43) and a higher
      frequency of allele epsilon 4 (22.12% vs. 10.38%, P = 0.030, OR = 2.45). Russians
      who suffered MI complicated by cardiogenic shock (CS) had a significantly higher
      frequency of genotype E3/4 and lower frequencies of genotype E3/3 and allele
      epsilon 3 as compared with MI patients without CS. In Tatars, genotype E4/4
      occurred at a frequency of 14.29% in patients who suffered MI under 45, and was
      not detected in healthy subjects of the same age (P = 0.024, OR = 17.85). Thus,
      the ApoE polymorphism was associated with higher risk of MI in Russians and
      Tatars under 45.

PMID- 12500533
TI  - [The regulatory role of the Hfq protein in bacterial cells].
AB  - Hfq (HF1) is a polyfunctional translational regulator of numerous bacterial
      mRNAs. Its physico-chemical properties, possible mechanisms regulating bacterial
      translation, and the effect of Hfq on transcription of several mRNAs are
      considered. A similarity of Hfq and eukaryotic mRNA splicing proteins is
      discussed. Data are reviewed on the roles of Hfq in poly(A) metabolism and
      formation of the bacterial nucleoid and on the Hfq interaction with untranslated
      regulatory RNAs.

PMID- 12500535
TI  - [The structure of the human oncogenesis-associated CKAP2 (LB1) gene].
AB  - The structure was described for human CKAP2, which codes for the cytoskeleton
      associated protein 2, is at the boundary of chromosome regions 13q14.3 and
      13q21.1, and is rearranged in various tumors. The CKAP2 exonintron structure was
      established by collating the nucleotide sequences of the cDNA and genomic clone
      AL359513 (GenBank) and analyzing the gene sequence with the GENSCAN program. The
      results were verified by amplifying gene fragments. CKAP2 comprises nine exons
      ranging 70-1442 bp and is about 22 kb in size (regulatory regions included). The
      CKAP2 promoter contains CCAAT (-39...-33) rather than the canonical TATA box, and
      harbors nine binding sites for six transcription factors. Thus, CKAP2 possesses
      all structural elements characteristic of eukaryotic genes. The results may be
      used to study the CKAP2 expression in normal and tumor cells in order to
      elucidate its role in carcinogenesis.

PMID- 12500536
TI  - [Diversity of mitochondrial DNA haplotypes in ethnic populations of the Volga
      Ural region of Russia].
AB  - The mtDNA polymorphism was analyzed in eight ethnic groups (N = 979) of the Volga
      Ural region. Most mtDNA variants belonged to haplogroups H, U, T, J, W, I, R, and
      N1 characteristic of West Eurasian populations. The most frequent were
      haplogroups H (12-42%) and U (18-44%). East Eurasian mtDNA types (A, B, Y, F, M,
      N9) were also observed. Genetic diversity was higher in Turkic than in Finno
      Ugric populations. The frequency of mtDNA types characteristic of Siberian and
      Central Asian populations substantially increased in the ethnic groups living
      closer to the Urals, a boundary between Europe and Asia. Geographic distances,
      rather than linguistic barriers, were assumed to play the major role in
      distribution of mtDNA types in the Volga-Ural region. Thus, as concerns the
      maternal lineage, the Finno-Ugric populations of the region proved to be more
      similar to their Turkic neighbors rather than to linguistically related Balto
      Finnish ethnic groups.

PMID- 12500537
TI  - [A new planarian extrachromosomal virus-like element revealed by subtraction
      hybridization].
AB  - A combination of suppression subtraction hybridization (SSH) and a new technique
      of mirror orientation selection (MOS) was used to compare the total DNA for two,
      sexual (SR) and asexual (AR), races of freshwater planarian Giradia tigrina.
      Several race-specific DNA fragments were found. A new element termed planarian
      extrachromosomal virus-like element (PEVE) was revealed in AR. The PEVE genome
      contains two unique regions, Ul and Us, which are flanked by inverted repeats.
      Two variants observed for the PEVE genome differ in combination of single- and
      double-stranded regions corresponding to Ul and Us. The PEVE genome codes for two
      helicases, one homologous to the circovirus replication initiation protein (Rep)
      and one corresponding to the helicase domain of papillomavirus E1. PEVE is
      nonuniformly distributed though the planarian body and is possibly replicated
      only in certain parenchymal cells.

PMID- 12500538
TI  - [Integration of the type D Mason-Pfizer monkey virus into the human chromosome].

PMID- 12500539
TI  - [Identification of the locus associated with diabetic nephropathy in type 1
      diabetes mellitus].
AB  - Polymorphic tetranucleotide microsatellites D3S1512, D3S1744, D3S1550, and D3S232
      were used to study the association of chromosome region 3q21-q25 neighboring the
      angiotensin II receptor type 1 gene (AT2R1) with diabetic nephropathy (DN) in
      diabetes mellitus type 1 (DM1). Allele and genotype frequencies were compared for
      DM1 patients with (N = 39) or without (N = 62) DN. Fisher's exact test with
      Bonferroni's correction revealed significant differences in frequencies of two
      D3S2326 alleles, one D3S1512 allele, and one allele and one genotype of D3S1550.
      No significant difference was observed with D3S1744. Thus, region 3q21-q25 proved
      tightly associated with DN in ethnic Russians with DM1 from Moscow.

PMID- 12500540
TI  - [The method of template construction for sequencing extended DNA fragments].
AB  - A rapid and convenient method was proposed for constructing insertional mutants
      in the sequencing of extended DNA fragments. The gist is insertion of an
      antibiotic resistance gene in plasmid DNA digested with DNase I. DNase I provides
      for a uniform distribution of insertion sites along the plasmid, and the
      background is low owing to antibiotic-based selection. The method requires
      neither high quality nor large amounts of plasmid DNA (which is especially
      important with low-copied plasmids), yields the results independent of the
      plasmid nucleotide sequence, and allows highly accurate analysis and ordering of
      the insertional mutants.

PMID- 12500541
TI  - [The context organization of functional regions in yeast genes with high-level
      expression].
AB  - With the example of yeast genes, context organization was compared for functional
      gene regions (promoter, 5'-UTR, 3'-UTR) and tested for association with the level
      of gene expression. Several parameters (nucleotide composition, dinucletoide
      content bias) proved to correlate with expression level, each functional region
      having its specific features. Context optimization of a functional region was
      assumed to be essential for highly efficient interaction with the expression
      system of the cell. Specific context features were considered as dispersed
      signals important for high-level gene expression.

PMID- 12500542
TI  - [Identification of two new p53 target genes through implementation of the
      modified chromatin immunoprecipitation method and inverse PCR].
AB  - Direct target loci for the transcription factor p53 were identified through the
      employment of a combination of a modified version of chromosomal
      immunoprecipitation and inverse PCR. Irradiation of Hela cells to drive DNA
      damage response was followed by sequential chromosomal immunoprecipitation
      utilizing antibodies which recognize the large subunit of RNA polymerase II and
      p53. Inverse PCR with degenerate oligonucleotides specific for the p53 binding
      site was subsequently performed on immunoprecipitated DNA and fragments
      containing putative p53 target genes were subcloned and sequenced. Two sequences
      were identified which contain near-consensus p53 binding sites as well as
      recognition sites for the core transcriptional machinery including RNA polymerase
      II and Sp1. Cotransfections of vectors containing these sequences linked to a
      reporter with p53 expression vectors resulted in stimulation of transcription.
      Application of the technology described herein may result in the identification
      of target loci for a wide variety of transcription factors.

PMID- 12500543
TI  - [Interaction of replication protein A and flap endonuclease 1 with DNA duplexes
      containing a nick or flap].
AB  - Nicks and flaps are intermediates in various processes of DNA metabolism,
      including replication and repair. Photoaffinity modification was employed in
      studying the interaction of the replication protein A (RPA) and flap endonuclease
      1 (FEN-1) with DNA duplexes similar to structures arising during long-patch base
      excision repair. The proteins were also tested for effect on DNA polymerase beta
      (Pol beta) interaction with DNA. Using Pol beta, a photoreactive dTTP analog was
      added to the 3' end of an oligonucleotide flanking a nick or a flap in DNA
      intermediates. The character and intensity of protein labeling depended on the
      type of intermediates and on the presence of the phosphate or tetrahydrofuran at
      the 5' end of a nick or a flap. Photoaffinity labeling of Pol beta substantially
      (up to three times) increased in the presence of RPA or FEN-1. Various DNA
      substrates were used to study the effects of RPA and FEN-1 on Pol beta-mediated
      DNA synthesis with displacement of a downstream primer. In contrast to FEN-1, RPA
      had no effect on DNA repair synthesis by Pol beta during long-patch base excision
      repair.

PMID- 12500544
TI  - [The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme
      DNA polymerase complexes].
AB  - A study was made of the correcting role of autonomous 3'-->5' exonucleases (AE)
      contained in multienzyme DNA polymerase complexes of rat hepatocytes or calf
      thymocytes. DNA was synthesized on phage psi X174 amber3 or M13mp2 primer
      templates, and used to transfect Escherichia coli spheroplasts. Frequencies were
      estimated for direct and reverse mutations resulting from mistakes made in the
      course of in vitro DNA synthesis. The mistake rate of the hepatocytic complex was
      estimated at 3 x 10(-6) with equimolar dNTP, and increased tenfold when proteins
      accounting for 70% of the total 3'-->5' exonuclease activity of the complex were
      removed. The fidelity of DNA synthesis was completely restored in the presence of
      exogenous AE (epsilon subunit of E. coli DNA polymerase III). Nuclear (Pol delta
      n) and cytosolic (Pol delta c) forms of DNA polymerase delta were isolated from
      calf thymocytes. The former was shown to contain an AE (TREX2) absent from the
      latter. As compared with Pol delta c, Pol delta n had a 20-fold higher exo/pol
      ratio and allowed 4-5 times higher fidelity of DNA synthesis. The mistake rate of
      DNA polymerase complexes changed when dNTP were used in nonequimolar amounts.

PMID- 12500545
TI  - [Mutational analysis of the conserved motif of the Arda anti-restriction protein
      encoded by self-transmissible IncI plasmid ColIb-p9].
AB  - A study was made of the functional role of the ArdA antirestriction motif (130
      LLADVPETVALYFD-143) conserved among all known Ard (alleviation of restriction of
      DNA) proteins, which are encoded by self-transmissible plasmids and specifically
      inhibit type I restriction-modification systems. Conserved residues of the motif
      were individually changed, and the resulting mutants tested for in vivo activity.
      Hydrophobic L130, L131, and V138 were substituted with negatively charged E;
      negatively charged D133, E136, and D143 substituted with hydrophobic V; and D127,
      D150, and D154 neighboring the antirestriction motif substituted with V. Four
      substitutions (L130E, L131E, V138E, and D143V) substantially (25-1000 times)
      reduced the ArdA activity. The other substitutions within or beyond the motif had
      no appreciable effect. Substitutions L130A and L131A each reduced the ArdA
      activity 10- to 20-fold, indicating that high hydrophobicity of L130 and L131 is
      important for the ArdA function. Thus, the antirestriction role of ArdA is indeed
      due to its conserved motif.

PMID- 12500546
TI  - [Kinetic parameters of hydrolysis of CpA and UpA sequences in an
      oligoribonucleotide by compounds functionally mimicking ribonuclease A].
AB  - Kinetic parameters of cleavage of CpA and UpA sequences in an oligoribonucleotide
      under the action of artificial ribonuclease ABL3C1 were measured. The compounds
      were built of RNA-binding domain B, catalytic fragment C, linker L3 comprising 3
      methylene groups, and aliphatic fragment A. The rate of cleavage of
      phosphodiester bonds in CpA sequence within decaribonucleotide UUCAUGUAAA was
      shown to be 3.4 +/- 0.2 times higher than in UpA sequence. The rate of cleavage
      of phosphodiester bonds were found to depend on substrate length: a thousandfold
      increase in cleavage rate constant was observed for CpA sequence in
      decaribonucleotide as compared with diribonucleotide monophosphate CpA. A slight
      decrease in the cleavage rates was observed for the reactions proceeding in
      different buffers at pH 7.0: imidazole > HEPES > phosphate > cacodylate. At the
      same time, the ratio of cleavage rates for CpA and UpA sequences remained
      constant.

PMID- 12500547
TI  - [Variable tandem repeat VcA of Vibrio cholerae].
AB  - Computer analysis revealed seven potential variable-number tandem-repeat (VNTR)
      loci in the Vibrio cholerae genome. Specific primers were designed to amplify
      locus VcA located on chromosome 2 and containing a TGCTGT repeat. The locus was
      found in all tested strains from a V. cholerae strain collection, the repeat
      number varying 3 to 23. In total, 14 VcA alleles were observed. The VcA locus was
      proposed as a marker for the molecular typing of V. cholerae strains.

PMID- 12500548
TI  - [The 42k protein of the shallot virus X participates in formation of the viral
      particles].

PMID- 12500549
TI  - [Neurogenesis in the adult mammalian brain].
AB  - The concept of the CNS cell composition stability has recently undergone
      significant changes. It was earlier believed that neurogenesis in the mammalian
      CNS took place only during embryonic and early postnatal development. New
      approaches make it possible to obtain new results overriding the dogma that
      neurogenesis is impossible in the adult brain. The present review summarizes the
      information about the neural stem cell. It has been demonstrated that new neurons
      are constantly formed in adult mammals, including man. In two brain zones,
      subventricular zone and denate gyrus, neurogenesis appears proceed throughout the
      entire life of mammals, including man. The newly arising neurons are essential
      for some important processes, such as memory and learning. Stem cells were found
      in the subependymal and/or ependymal layer. They express nestin, and have a low
      mitotic activity. During embryogenesis, the stem cell divides asymmetrically: one
      daughter cell resides as the stem cell in the ependymal layer and another
      migrates to the subventricular zone. There it gives rise very fast to a pool of
      dividing precursors, from which neural and glial cells differentiate and migrate
      to the sites of final localization. The epidermal and fibroblast growth factors
      act as mitogens for the neural stem cell. The neural stem cell gives rise to the
      cells of all germ layers in vitro and has a wide potential for differentiation in
      the adult organism. Hence, it can be used as a source of various cell types of
      the nervous tissue necessary for cellular transplantation therapy.

PMID- 12500550
TI  - [The principles of data formalization for building the genetic-morphological
      model of shoot development in flowering plants].
AB  - Shoot system of a plant can be divided into elementary molecules composed of
      phyllome, internode, and meristem of the lateral bud. The capacity of plants for
      open growth is manifested as multiple reproductions of the modules. These main
      principles of plant structural organization can be used to formalize and
      integrate the data from various disciplines studying the shoot development-
      genetics of development, morphology, etc. At the example of model species
      Arabidopsis thaliana we show that the data on genetic control of shoot
      development can be considered in terms of individual modules reorganization.
      Several variants of the modules structural reorganization are allowed: reduction
      or transformation of phyllome, change in the internode length, and triggering
      active/inactive status of the lateral shoot meristem. Each variant of the module
      structure corresponds to specific pattern of genes activity. Such integration of
      the data on genetic and structural aspects of morphogenesis can form a basis for
      mathematical modeling of plant development.

PMID- 12500551
TI  - [Restorative morphogenesis in vitro of the annual Medicago species in presence of
      benzylaminopurine].
AB  - Four annual medick species (Medicago orbicularis (L.) All., M. rigidula (L.)
      Desr., M. scutellata (L.) Miller, and M. rugosa Desr.) were used as model objects
      for studying the spectrum of morphogenetic reactions in vitro. The seeds were
      incubated on nutrient media with benzylaminopurine at different concentrations
      until germination and, thereafter, the explants of seedlings were cultivated in
      order to obtain primary calluses and morphogenetic structures. Normal and
      abnormal (with reduced root and/or apex) seedlings were cultivated in the
      presence of benzylaminopurine. Further cultivation of explants from the seedlings
      of both types showed a considerable intra- and interspecific polymorphism by the
      capacity for callusogenesis, frequency of primary restorative reactions, and
      pattern of microreproduction in vitro. In the control (the seeds were incubated
      on a hormone-free medium), no cases of microreproduction by way of organogenesis
      or somatic embryogenesis were observed. In all experimental variants, the
      restorative reactions preceded microreproduction in vitro.

PMID- 12500552
TI  - [The role of H+/- ATPase and alternative oxidase in the regulation of
      intracellular pH at the different stages of development of the tobacco male
      gametophyte].
AB  - In order to determine the role of the plasma membrane H(+)-ATPase and alternative
      oxidase (alternative pathway of respiration) in the regulation of intracellular
      pH during development of the tobacco male gametophyte, we studied the changes in
      pH due to the inhibition of these enzymes by orthovadanate and benzhydroxamic
      acid, respectively. The inhibition of these enzymes decreased the intracellular
      pH at all three studied stages of the male gametophyte development: middle and
      late binuclear pollen grains and activated mature pollen grain. The data obtained
      suggest that H(+)-ATPase and alternative oxidase are involved in the regulation
      of intracellular pH of the pollen grain during its differentiation and activation
      that precede germination. At the same time, during the recovery of intracellular
      pH after its acidification by propionic acid, it was found that other mechanisms,
      not related to the above mentioned, greatly contribute to the regulation of pH.

PMID- 12500553
TI  - [Cytogenetic aberrations in the cells of liver and spermatogenetic epithelium in
      senescence accelerated SAMP1 and SAMR1 mice].
AB  - It was shown that during ontogenesis, the mice prone to (SAMP1) and resistant
      against accelerates senescence did not differ substantially in the frequency of
      cytogenetic aberrations in the hepatocytes and spermatogenic cells (spermatozoa
      and circular spermatids). These data suggest that in the mice of both lines, the
      processes of appearance, development, and functioning of complex biological
      systems, such as liver and testis, take place against the background of high
      genetic instability. The role of genetic instability in senescence is discussed.

PMID- 12500554
TI  - [Epidermal growth factor stimulates proliferation and DNA synthesis in ciliate
      cells].
AB  - We studied the effect of murine epidermal growth factor on cell proliferation and
      DNA synthesis in macronuclei of ciliate Tetrahymena pyriformis G1. Mitogenic
      effect of epidermal growth factor on proliferation-induced tetrahymena cells has
      been revealed. This effect is due to the induced progression of cells at G1 and,
      consequently, their earlier entering DNA synthesis phase of the first cell cycle.
      Epidermal growth factor had no mitogenic effect on the resting cells from
      stationary culture (G0 phase) whose development is independent of the growth
      factors in the medium.

PMID- 12500555
TI  - [Introduction of the human recombinant angiogenin at the early stages of
      postnatal development inhibits the growth of mice].
AB  - We studied the influence of recombinant DNA containing the cloned angiogenin
      gene, plasmid DNA without angiogenin gene, and purified recombinant angiogenin
      injected to Tg8 mice at the age of two days on the body mass of 28- and 40-day
      old mice. The body mass of mice that were injected with the cloned angiogenin
      gene or purified angiogenin was less than in the control mice. The body mice of
      Tg8 mice injected with recombinant DNA containing the cloned angiogenin gene did
      not increase from day 2 to day 40, while in the mice with purified recombinant
      angiogenin and control mice it increased by 24 and 57%, respectively. These data
      suggest that the elevated level of angiogenin at the early developmental stages
      inhibits the increase of body mass. The effect we described as related, in al
      likelihood, to the known inhibitory effect of angiogenin on protein synthesis.

PMID- 12500556
TI  - [Effects of the antagonist of the classical progesterone receptor on ovulation
      and maturation of common frog (Rana temporaria L.) oocytes in vitro].
AB  - Progesterone induces maturation and ovulation of amphibian oocytes and, in the
      process, binds to the receptors in oocytes and follicle cells. It is still
      unclear to what extent the progesterone receptors in these cells are similar. We
      tried to answer this question using RU486, an antagonist of the classical
      mammalian progesterone receptor. Pretreatment of the ovarian follicles with RU486
      (1-20 microM) does not affect the maturation or ovulation of the common frog
      oocytes stimulated in vitro by pituitary hormones or progesterone and even
      increases (at low concentrations) the percentage of maturated and ovulated
      oocytes. In addition, RU486 (5-40 microM) stimulates the oocyte maturation and
      ovulation in a dose-dependent manner. Pretreatment of the follicles with
      actinomycin D (5 microM) inhibits both RU486-stimulated processes. An increase in
      RU486 concentration overcomes the inhibitory effect of actinomycin D on oocyte
      maturation. On the contrary, the inhibitory AD effect on oocyte ovulation does
      not depend on the RU486 concentration. RU486 stimulates the maturation of both
      follicle-enclosed and "denuded" oocytes. However, the sensitivity of the latter
      to RU486 is much lower and its effect on the denuded oocyte is not inhibited by
      actinomycin D. The data obtained suggest that in amphibians, unlike in mammals,
      RU486 is an agonist of progesterone. It stimulates the transcription-independent
      maturation of denuded oocytes (membrane receptor) and transcription-dependent
      ovulation (classical receptor). In addition RU486 can stimulate (at certain
      doses) the transcription-dependent maturation of follicle-enclosed oocytes.

PMID- 12500557
TI  - [The theory of phyllotaxis. II. Crystallographic interpretation of the
      interrelation between lower and superior phyllotaxis forms].
AB  - Cross-opposite phyllotaxis forms are defined as superior with respect to the
      alternate ones and verticillate phyllotaxis forms as superior with respect to the
      opposite ones. Different phyllotaxis forms can be interpreted as a result of
      stretching of crystal-like structures of the embryo formed by dense packing of
      rudiments. Based on hypothetical concepts of the properties of plant rudiments
      and embryos, possible mechanisms of the formation of superior phyllotaxis forms
      from the lower ones have been analyzed. It was shown that the superior
      phyllotaxis forms can be considered as the results of additive summation of the
      lower forms. The theoretical conclusions are confirmed by the examples of
      polymorphic phyllotaxis in conspecific plants and by the facts of accidental
      splitting of superior phyllotaxis forms into the corresponding lower forms in
      nature and in experiment. The mechanisms underlying the formation of multiple
      forms of helical phyllotaxis have been proposed. The concept of a new type of
      mixed hexagonal-tetragonal phyllotaxis has been formulated and the mechanism of
      its formation has been considered. The forms of corn grain packaging in the
      corncob and leaf arrangement on the strawberry tomato stem are given as examples
      of true hexagonal-tetragonal phyllotaxis in nature.

PMID- 12500558
TI  - [Vibrational structure of absorption spectra of water in visible region].
AB  - The results of the study of the temperature dependence of water absorption
      spectra in the visible region and in the region of vibrational overtones are
      discussed.

PMID- 12500559
TI  - [Slow photoinduced changes in reaction centers of Rhodobacter sphaeroides R-26 by
      holographic interferometry].
AB  - Using the on-line holographic interferometry, changes in the refraction index of
      illuminated solutions containing the Rhodobacter sphaeroides R-26 reaction
      centers isolated from membranes by detergents of ionic and nonionic nature were
      registered. Factors affecting the refraction index of these solutions were
      analyzed. It was shown that the photoinduced changes in this parameter are due to
      structural changes in the molecular complex of reaction centers. The results of
      measurements of the kinetics of absorption spectra at lambda = 865 nm for two
      detergent types are presented, which coincide qualitatively with the results of
      holographic measurements. The change in the volume of the molecular complex of
      reaction centers was estimated to be 0.1 divided by 1%.

PMID- 12500560
TI  - [Interaction of riboflavin and hemoproteins with organic free radicals and
      superoxide anions generated in the ultrasound field].
AB  - The reduction of ferricytochrome c to the ferro form in aqueous alcohol solutions
      in air by the action of ultrasound and the complete inhibition of this process in
      the presence of superoxide dismutase indicate the generation of superoxide
      anions. Further exposure to the ultrasonic field leads to a reverse process of
      oxidation of the cytochrome c ferro form to the ferri form by hydrogen peroxides
      and organic peroxides. The addition of catalase protects the cytochrome c ferro
      form from oxidation to the ferri form. The oxidized form of riboflavin
      effectively interacts with organic free radicals and superoxide anions to produce
      a leuko form, which is easily oxidized by air oxygen or the ferri forms of
      hemoglobin and cyt c to form riboflavin and hydrogen peroxide or the ferro forms
      of heme-containing proteins, respectively. The recurrence of redox reactions in
      the presence of riboflavin, organic free radicals, and O2 and the ferri forms of
      heme-containing proteins suggests that riboflavin can play a role of an
      antioxidant in the organism. It is supposed that, due to interaction with
      superoxide anions, riboflavin stabilizes the NO level in the organism under
      conditions of increased superoxide anion generation and (or) decreased superoxide
      dismutase activity. A possible role of riboflavin in the modulation of toxic and
      signal pathways of nitrogen oxide is discussed.

PMID- 12500561
TI  - [Are synthetic proteins relevant to the problem of protein folding?].
AB  - The possibility to derive the analogs of native proteins by the chemical
      synthesis is considered to be a serious argument for the concept of
      posttranslational protein folding. The present paper analyzes for the first time
      chemically synthesized proteins to reveal whether they are relevant to the
      problem of protein folding. The results enable the following conclusions to be
      drawn. The acquisition of the peculiar conformations by the chemically
      synthesized proteins to exhibit the specific functions is conditioned by the
      highly marked features of the secondary and tertiary structures of the
      corresponding native proteins. These features will make themselves evident only
      if favorable conditions are carefully chosen during the experiments for each
      individual protein. Thus, in our opinion, the possibility to derive a synthetic
      protein is hardly evidence for the posttranslational folding of proteins.

PMID- 12500562
TI  - [Interactions between nucleic acid bases. New parameters of potential functions
      and energy minima].
AB  - The parameters of atom-atom potential functions suggested by one of the authors
      in 1979-1986 were slightly changed. The changes were performed to achieve a
      better agreement with experimental data of interaction energy values in global
      minima and hydrogen bond lengths. These changes resulted in better accord with
      experimental values of distances between the layers in DNA monomer crystals and
      between the base pairs in oligonucleotide duplexes. The refined potential
      functions were used to calculate the energy of interactions between nucleic acid
      bases in various mutual positions. The calculations revealed a few types of
      mutual base arrangements in minima of interaction energy for each pairwise base
      combination. A new type of minima was found, which correspond to a nearly
      perpendicular arrangement of base rings and the formation of the intermolecular
      hydrogen bond.

PMID- 12500563
TI  - [Study of effect of water on the interaction of DNA and actinocin derivatives
      with various aminoalkyl chain length by infrared spectrophotometry and computer
      modeling].
AB  - A comparative study of the effect of water on the interaction of DNA with
      actinocin derivatives having different numbers of methylene groups in side chains
      was performed by IR spectroscopy. It was found that, as relative humidity
      increases, water molecules simultaneously bind to hydrate-active sites of DNA and
      ligands. The absorption band at v = 1137 cm-1, caused by oscillations of the C-O
      and P-O groups of atoms in the DNA-ligand complex having two methylene groups, is
      due to the interactions between the cationic groups of the ligand and the sugar
      phosphate backbone of DNA, which may be one of the reasons for the high stability
      of this complex. Using computer simulation of interaction of DNA fragments and
      actinocin derivatives in water environment, molecular models of the formation of
      their complexes for two ways of binding were constructed.

PMID- 12500564
TI  - [Two-photon excitation fluorescence spectrum of the light-harvesting complex LH2
      from Chromatium minutissimum within 650-745 nm range is determined by two-photon
      absorption of bacteriochlorophyll rather than of carotenoids].
AB  - Two-photon fluorescence excitation spectra of the peripheral light-harvesting
      complex LH2 from the purple photosynthetic bacterium Chromatium minutissimum were
      examined within the expected spectral range of the optically forbidden S1 singlet
      state of carotenoids. LH2 preparations isolated from wild-type and carotenoid
      depleted cells were used. 100-fs laser pulses in the range of 1300-1490 nm with
      an energy of 7-9 mW (corresponding to one-photon absorption between 650 and 745
      nm) were used for two-photon fluorescence excitation. It was shown that two
      photon fluorescence excitation spectra of LH2 complex from wild and carotenoid
      depleted cells are very similar to each other and to the two-photon fluorescence
      excitation spectrum of bacteriochlorophyll a in acetone. It was concluded that
      direct two-photon excitation of bacteriochlorophyll a determines the fluorescence
      of both samples within the 650-745 nm spectral range.

PMID- 12500565
TI  - [Photosystem reaction centers and structural organization of chloroplasts in
      chlorotica mutants of Pisum sativum L].
AB  - Chlorophyll-protein complexes of photosystems (PS), as well as ultrastructural
      arrangement of chloroplasts in pea leaves of the primary cultivar Torsdag and
      mutants chlorotica 2004 and 2014 were studied. It was shown that both mutants
      accumulated 80 and 55% of chlorophyll, respectively, and were able to synthesize
      all of four types of photosystems complexes. The value of the light-harvesting
      antenna in mutant 2014 was close to the control one, and in mutant 2004 it
      increased significantly (by 30%). These changes were caused by a proportional
      decrease, 40-50%, of any complexes in mutant 2014, whereas the number of PS I
      reaction centers in mutant 2004 decreased by 50% and the reaction centers of PS
      II complexes were almost completely retained. It was established that the
      proportional decrease of PS I and PS II complexes in mutant chlorotica 2014 was
      followed by a partial reduction of the entire membrane system in chloroplasts,
      but with a good development of both granal and intergranal sites of thylakoids.
      On the contrary, the loss of complexes of PS I reaction centers in mutant
      chlorotica 2004 led to a reduction of unstacked sites of thylakoids in
      chloroplasts. It was concluded that the disturbance of the lateral orientation of
      the membrane system of chloroplasts is associated with the loss of complexes of
      reaction centers of PS I, which is predominantly localized in unstacked sites of
      thylakoids.

PMID- 12500566
TI  - [Fluorescence, chlorophyll shape and number of photosystem reaction centers I and
      II in chlorotica mutants of Pisum sativum L].
AB  - The fluorescent and absorbing properties of chloroplasts and pigment-protein
      complexes isolated by gel electrophoresis from pea leaves of the cultivar Torsdag
      and the mutants chlorotica 2004 and 2014 were studied. From the absorption and
      fluorescence spectra of chlorophylls and their 2nd derivatives, the range of
      their changes in the native state at 23 degrees C and specific maxima of
      fluorescence and the forms of chlorophyll of individual complexes at -196 degrees
      C were found. It was found that in mutant chlorotica 2004 the intensity of
      fluorescence of long-wave band at 745 nm (23 degrees C) and the maximum--at 728
      nm (-196 degrees C) belonging to the light-harvesting complex I increased.
      Nevertheless, the accumulation of the chlorophyll forms in this mutant at 690,
      697 and 708 nm, which make an antenna of reaction centers of photosystem (PS) I
      decreased. No spectral differences from the spectrum of the wild type were found
      in mutant chlorotica 2014, except for a weakening of interaction between the
      complexes of PS I and PS II. It was shown by gel electrophoresis that both
      mutants were capable of synthesizing any chlorophyll-protein complexes. However,
      the analysis of the photochemical activity of reaction centers of PS I and PS II
      as well as calculations of the value of the photosynthetic unit and the number of
      reaction centers of the photosystems enabled us to conclude that the quantity of
      the reaction centers of PS I in the mutant chlorotica 2004 was 1.7 times lower
      due to disturbance of mutations in biosynthesis or the formation of the
      chlorophyll a-protein complex of PS I. No primary effect of mutation of
      chlorotica 2014 was established. Proportional changes of all parameters in this
      mutant gave us the ground to consider them as secondary ones, which are caused by
      a decrease in chlorophyll content by half.

PMID- 12500567
TI  - [Kinetic model of primary processes of photosynthesis in chloroplasts. Fast phase
      of chlorophyll fluorescence induction under light of various intensity].
AB  - A kinetic model was developed, which describing the system of generation and
      consumption of the transmembrane electrochemical proton potential delta mu H+ in
      primary photosynthetic processes. The model describes the catalytic cycles of
      photosystems I and II and the cytochrome b/f complex, as well as the ATP
      synthesis and passive leakage of H+, K+ [symbol: see text] Cl- ions through the
      thylakoid membrane. The dependence of the electron transfer rates on the value of
      transmembrane electric potential was taken into account. The model was applied to
      describe the experimental data on the registration of the fast phase of
      fluorescence induction. The model gives a realistic description of the fast phase
      of induction curves at different light intensities (from high to low).

PMID- 12500568
TI  - [Conflict: induction-inhibition of transgene bacteria luminescence in studying
      expression of lux-genes].
AB  - The relationship between the induction of the luminescent operon of lux-genes
      fused with the naphthalene and salicylate degradation genes and the inhibition of
      light emission caused by these compounds was studied. The quantitative
      correlations between these processes manifest themselves in the fact that light
      intensity linearly increased in a narrow concentration range of the inductor and
      then decreased due to the inhibition of the luminescence reaction itself, which
      is not related to the regulation of expression of lux-genes.

PMID- 12500569
TI  - [Interaction of membrane proton conductivity, membrane and oxidation-reduction
      potential in Escherichia coli].
AB  - It was shown that the proton conductivity of Escherichia coli membranes depends
      on pH and other conditions of bacterial growth. It is considerably lower in cells
      fermenting glucose and accomplishing the nitrate-nitrite respiration compared
      with cells accomplishing the oxygen respiration. Proton conductivity increases
      substantially with decreasing pH of medium. It was found that proton conductivity
      is related to the redox and membrane potentials of cells. The energy-dependent
      flux of protons from cells and the ATPase activity of membrane vesicles
      considerably vary depending on whether bacteria are grown under aerobic or
      anaerobic conditions. The H+ flux from cells fermenting glucose (pH 7.5) was 1.7
      times greater than the H+ flux from cells that accomplish the nitrate-nitrite and
      oxygen respiration. The N,N'-dicyclohexylcarbodiimide (DCCD)-sensitive ATPase
      activity increased 2.5 times as K+ concentration increased to 100 mM (including
      residual K+ in potassium-free medium). The DCCD-sensitive ATPase activity
      considerably decreased with decreasing pH of medium, whereas the ATPase activity
      that was not suppressed by DCCD was stimulated. These results can be used for
      establishing the relationship between membrane proton conductivity and the energy
      dependent H+ flux and ATPase activity.

PMID- 12500570
TI  - [Monovalent ion permeability of model bilayer membranes based on lipids from
      tissues of various vertebrates].
AB  - The ionic permeability of model bilayer membranes prepared from total lipids of
      the brain, heart, liver, and muscles of four species of higher vertebrates was
      studies. The electrical conductivity and potential of membranes breakdown were
      measured in KCl, NaCl, and LiCl solutions. It was found that the permeability for
      potassium ions of bilayer lipid membranes from the lipids of nervous tissue
      decreases in the row of poikilothermal vertebrates and increases in mammals. A
      reverse regularity was observed for membrane stability, which manifested itself
      as an increase in membrane breakdown in the order fish-amphibian-reptile and a
      decrease in membrane breakdown in mammalian membranes. It was shown that, in most
      cases, the the permeability of bilayer lipid membranes for K+ ions is higher than
      for Na+ and Li+.

PMID- 12500571
TI  - [Study of P-glycoprotein effect on the lipid monolayer properties by the Langmuir
      Blodgett technique].
AB  - Expression of the P-glycoprotein (Pgp) is proved to be one of the main reasons
      for the development of the multidrug resistance (MDR) phenotype by cancer cells.
      The effect of Pgp on the properties of lipid monolayers was studied using
      membrane fractions of sensitive and Pgp over-expressing multidrug resistance
      cancer cells containing 11, 24 or 32% of Pgp relative to the total content of
      membrane proteins. The effect of the Pgp membrane concentration on the properties
      of monolayers prepared from the membrane fractions was analyzed by the Langmuir
      Blodgett method. The subphase composition was found to play a critical role in
      the stability of monolayers at any Pgp concentration. The optimal subphase
      comprised 10 mM tris-HCl buffer, pH 6.5, which made it possible to create very
      stable monolayer films with the pressure of collapse of about 30-40 mN/m.
      Monolayers prepared from membrane fractions of sensitive cells and cells
      containing the maximum (32%) amount of Pgp were found to be much more stable
      compared with fractions comprising 11 or 24% of Pgp. The analysis of monolayer
      compression dynamics revealed three distinct stages: (1) the self-organization of
      lipid molecules, which is characterized by an abrupt change of surface potential;
      (2) the compression of Pgp molecules at the constant potential of monolayers; and
      (3) the compression of lipid molecules, which is characterized by a quasilinear
      increase of both pressure and surface potential. It was shown that the specific
      surface areas of monolayers formed from sensitive and Pgp-enriched membranes
      containing 11 or 24% of Pgp are very similar, whereas the surface area of the
      monolayer formed from membranes containing 32% of Pgp is nearly 1.5-fold greater.
      This fact may reflect the effect of the threshold rearrangement of the structure
      of lipid molecules or cooperative modifications of lipid-Pgp interactions induced
      by the increase in the Pgp content from 24 to 32%. The effect of verapamil, a
      well-known Pgp modulator, on the properties of monolayers was studied. It was
      show that verapamil is able to induce changes of the surface of Pgp-containing
      monolayers, and these modifications are maximal at the Pgp:verapamil 1:1 molar
      ratio. The data present the first experimental evidence for the possible
      intervention of Pgp modulator into the processes of lipid-lipid or lipid-Pgp
      cooperative interactions within Pgp-enriched membranes.

PMID- 12500572
TI  - [Functional activity of ganglion neurons from the pond snail upon temperature
      variations].
AB  - Changes in the functional state of the synthetic apparatus of neurons of the
      peripharyngeal ring of the mollusk Lymnaea stagnalis upon elevating the
      temperature of the habitat from 4 to 18-22 degrees C were studied. In the first
      series of experiments, it was found that the synthetic activity of neurons of the
      great and small parietal, visceral, and pleural ganglia increases on the average
      by 70%. In the second series of experiments, changes in the average synthetic
      activity for all ganglia at 4.0, 6.5, 13.0, 16.8, 20.5, 21.5, 21.9, and 22.0
      degrees C were studied. The increase in the synthetic activity of neuron
      cytoplasm (35% higher than the control values at 4.0 degrees C) was maximal at
      13.0 degrees C; then the synthetic activity decreased to reach the level 20%
      higher than the control. The physiological range of temperature-dependent changes
      in the functional state of neurons was determined.

PMID- 12500573
TI  - [A model for evoked activity of hippocampal neuronal population].
AB  - A system of equations governing the activity of hippocampal neuron populations is
      proposed. This continual firing-rate model is aimed to simulate evoked potentials
      and synchronous wave activity of the neural tissue. The populations of excitatory
      and inhibitory neurons and the types of synaptic receptors are distinguished. The
      model is based on the idea of control and averaging of Hodgkin-Huxley equations,
      a simple model of a threshold elicitation of population action potential bursts,
      approximations of synaptic currents by the second-order differential equations,
      and hyperbolic partial derivative equation of axonal excitation propagation. The
      model was fitted to intracellular cordings of postsynaptic potentials and
      postsynaptic currents in CA1 of rat hippocampal slices.

PMID- 12500574
TI  - [Changes in human biliary vesicle sizes in pathological states].
AB  - Changes in the sizes of aggregates of bile vesicles at various nucleation factors
      were studied by the method of dynamic spectroscopy. It was found that the sizes
      of bile vesicles in chronic cholecystitis vary from 90 to 200 nm. It was shown
      that the presence of a large fraction of bile vesicles characterized by a higher
      cholesterol concentration can serve as a criterion of acuteness of cholecystitis
      and the intensity of lithogenesis.

PMID- 12500575
TI  - [Changes in dynamics of phase transitions in various liquids by recording of
      acoustic mechanical impedance of a drying drop].
AB  - A method of studying multicomponent liquids is proposed, which is based on
      recording the dynamics of the acoustomechanical impedance of a drop that dries up
      on the surface of a quartz resonator oscillating with an ultrasound frequency.
      The magnitude of the acoustomechanical impedance is an integral characteristic of
      the physical properties of the drop such as viscosity, composition, surface
      tension, moistening, and inner structure. Using liquids of different types as an
      example, it was shown that each liquid possesses its individual "portrait", which
      is determined by the phase transitions. The method can be used for the screening
      identification of liquids (determining the degree of consistency with the
      standards) in solving a number of scientific and practical problems, as well as
      in medicine.

PMID- 12500576
TI  - [Nonmonotonous metabolic response of mammalian cells and tissues to ionizing
      radiation].
AB  - Changes in the activity of ornithindecarboxylase in various tissues and in the
      amount of catecholamine in rat hypothalamus by the action of acute and chronic
      ionizing radiation were studied. A nonmonotonous relationship between the
      metabolic parameters of animal tissues and cells and the radiation dose was
      revealed. It was assumed that the nonmonotonous character of the dose-response
      dependence results from the nonmonotonous time course of the metabolic response
      to irradiation. It was also assumed that living systems have the property of
      responding to stress agents by nonmonotonous changes in metabolism. In the case
      of acute irradiation, this response manifests itself as oscillations of metabolic
      parameters about the control. The oscillations occur with a particular amplitude
      and periods, which vary with radiation dose, and damp out with time. As a result,
      in a fixed time interval, the dose-response curve may be nonmonotonous. Reverse
      dose-response relationships are also possible. In the case of chronic
      irradiation, the metabolic and functional parameters oscillate throughout
      irradiation time, and a modification of the response occurs. A prolong exposure
      to ionizing radiation causes strong changes in the metabolism of lipids of cell
      membranes, organelles and chromatin, as well as in the functional properties of
      some mammalian cells and tissues. The necessity of constructing quantitative
      models for explaining the nonmonotonous dose-response dependence is discussed.

PMID- 12500577
TI  - [Medusomyces (tea fungus): scientific history, composition, physiology, and
      metabolism].
AB  - The literature data on medusomyces published since 1913 are discussed. Different
      versions of appearance and distribution of this microorganism are considered. The
      features of its structure, metabolism and growth conditions are analyzed. It is
      shown that the tea fungus is a symbiosis is of several sorts of yeast and acetic
      acid bacteria. Evidence is presented indicating that fermented tea fungus has a
      therapeutic effect and can be applied in medicine. It was proved, that the
      antimicrobial properties of tea fungus metabolic products are due to the presence
      of particular antibiotic substances. The regularities of the biosynthesis of
      these substances and the pathways of its stimulation were studied. The results
      obtained will lead to the large-scale use of tea fungus in biotechnology. The
      fungus has unique adaptation properties, as confirmed by experiments on
      cultivation of the organism on deuterium oxide (D2O) and in the conditions of
      "cold stress". It is suggested that medusomyces is a unique model for the
      investigation of the phenomenon of symbiosis.

PMID- 12500578
TI  - [Structural and molecular origin of information recording/reading].
AB  - On the basis of experimental data on the thermoinduced state of water dispersions
      of natural and synthetic phospholipids in the presence of nootropic agents, a new
      phenomenological molecular mechanism of information recording/reading was
      proposed. The mechanism is based on the polymorphism of membrane lipids. A new
      approach, to the problem of memory was suggested, which considers memory as an
      information data bank and separates this concept from the concept of the
      mechanisms of information recording/reading.

PMID- 12500579
TI  - [Can an organism select new valuable information from environment].
AB  - The process of selecting new information by the organism ("learning") was
      studied. To take a decision, key patterns have to be set a priori, and so
      knowledge accumulation (learning) based on pattern recognition is impossible. It
      was shown that the only physical process that, takes place during the emergence
      of an external signal is the triggering of a priori programmes. An equivalent
      biophysical scheme of pattern recognition and taking the decisions by the
      organism was developed in which a signal received by the receptor leads to the
      synthesis of one of possible catalysts. The catalyst starts up the corresponding
      thermodynamic process. The information contained in the organism does not change
      during this process.

PMID- 12500580
TI  - [Learning and selection create new information].
AB  - Comments on the article of A.V. Melkikh "Can the Organism Select New Valuable
      Information from Environment?" are given.

PMID- 12500581
TI  - [Probability mechanism of species adaptation].
AB  - A variant of mathematical description of the structure of a population was
      proposed. A possible mechanism of selection with respect to population structure
      was shown by a mathematical method. The dependence of the population
      heterogeneity on environmental factors and the relationship between heterogeneity
      and selection were considered. It is recommended to realize the conception of
      threshold values in each experiment of "dose-test-effect" type.

PMID- 12500582
TI  - Long-term care insurance matures as a benefit.
AB  - Forty-eight percent of U.S. businesses now offer long-term care insurance (LTCI)
      coverage, an increase of 15% since 1998. As more organizations realize the added
      value of LTCI in the employee benefit package, they have also found that
      motivation to buy varies with employee financial standing, gender and age, and
      that targeted employee education as part of retirement planning is essential.

PMID- 12500583
TI  - Long-term care insurance: an essential employee benefit.
AB  - Growing numbers of employers are embracing long-term care insurance (LTCI) as an
      important new addition to their employee benefits package due to aging baby
      boomers, tax favorable legislation, the need for employee retention and rising
      costs of care. Even the best retirement plans can be gutted by the high costs of
      long-term care. The authors identify key components of LTCI and offer guidelines
      for selecting an LTCI company.

PMID- 12500584
TI  - Integrating contributory elder-care benefits with voluntary long-term care
      insurance programs.
AB  - Caregiving for aging parents or other disabled family members takes a heavy toll
      on work and family life, as well as the company bottom line. Research reveals
      that the two primary responses to elder-care issues in the workplace are employer
      paid consultation and referral programs, and employee-paid long-term care
      insurance (LTCI) plans.

PMID- 12500585
TI  - Genomics and proteomics: the next generation of health care.
AB  - Biotechnology research will dramatically impact health care, and the
      pharmaceutical industry in particular, in the coming decade. Health outcomes may
      be improved in a cost-effective manner through the ability to selectively
      prescribe medications; safer, more effective treatment may reduce long-term
      health care costs. As genetic testing becomes the standard of care, new
      challenges will surface around how genetic information will be used or misused,
      and how and where health care dollars are spent.

PMID- 12500586
TI  - From managed care to "financed care".
AB  - Paying for health care in the new millennium may require fundamental
      restructuring of how costs are managed to avoid rationing and a government
      takeover.

PMID- 12500587
TI  - The searchers, II: How consumers can find cost-effective, quality health care.
AB  - The original "Searchers" article appeared in the March 2000 issue of Employee
      Benefits Journal. It described the use of a patient satisfaction survey at
      Southwest Texas State University (SWT) to assist employees at the annual open
      enrollment period to better select their managed care organization (MCO). This
      article revisits that process, but further describes the subsequent publication
      of a recommended list of preferred physicians and the use of the peer review to
      report consumer concerns about the performance of individual physicians.

PMID- 12500588
TI  - The case for an actuary.
AB  - The author describes the role of the actuary, the need for qualified actuaries
      and how to find them. Qualified actuarial help, in the form of a Fellow of the
      Society of Actuaries (FSA), is necessary to ensure the best outcome when setting
      annual premium rates and realistic budgets for self-funded group benefit plans.

PMID- 12500589
TI  - Evaluating the impact of child safety seat check-up events on parental knowledge.
AB  - Riding unrestrained is the greatest risk factor for death and injury among
      children in motor vehicles. Restraining a child can reduce the risk of death for
      that child by up to 71%. However, despite increased awareness, child safety seat
      usage rates are still disturbingly low. The purpose of this study was to evaluate
      the impact that child safety seat check-up events have on parental knowledge on
      child safety seats and installation. The subjects for this study were 101
      parents/caregivers who attended child safety seat check-up events in northwest
      Arkansas from May 2000 through June 2001. A 20-item survey was conducted via the
      telephone. Results showed that the check-up events in northwest Arkansas have had
      an impact on self-efficacy. The participants of the events were primarily
      Caucasian and females in the 30-34 age group. Nine of 10 subjects scored in the
      high knowledge category. Conclusions are that check-up events do have an impact
      on parental knowledge and are accepted by the target group. Additionally,
      participants believed that car seats are of great importance and do protect their
      children in the event of a crash.

PMID- 12500590
TI  - Aortic stenosis: a practical review.

PMID- 12500591
TI  - New federal initiative features public reporting of nursing home data.

PMID- 12500592
TI  - The call of the wild. It's open season for those physicians who hunt for more
      than what ails you.

PMID- 12500593
TI  - Rates and pillage.

PMID- 12500594
TI  - Perpetual motion.

PMID- 12500595
TI  - Overseas recruitment. Rich pickings.
AB  - A recruitment drive in Germany resulted in the appointment of three consultant
      anaesthetists and one consultant orthopaedic surgeon for a small acute trust in
      the north east of England, at a cost of about Pounds 10,000. The initiative
      involved a senior management team making several visits to Germany to talk to
      prospective applicants. Shortlisted applicants and their partners were invited
      for a familiarisation tour of the local area. The initiative met with initial
      opposition from within the trust but the appointed doctors are now well
      integrated. Trusts hoping to recruit from abroad should not underestimate the
      amount of practical support that will be needed by those moving from other
      countries.

PMID- 12500596
TI  - Overseas recruitment. The Spanish acquisitions.
AB  - A pilot project, funded by the Department of Health, resulted in the recruitment
      of 17 Spanish GPs to practices in Liverpool and Manchester. The doctors are
      employed on two-year contracts with a salary of Pounds 45,000. The scheme has
      shown that Spanish GPs are not experienced in interviewing potential employers,
      or negotiating job plans. The initiative includes a four-month induction period
      in a training practice. The importance of language support and a senior champion
      for the scheme are key factors.

PMID- 12500597
TI  - US healthcare. The writing's on the wall.

PMID- 12500598
TI  - [Arterial thrombogenesis: the crucial role of platelets].
AB  - Better understanding of platelet function helps not only the integration of many
      available data, because the fact that platelets play a decisive role in arterial
      thrombosis, but also to determine the pharmacological management of these
      phenomena. Globally, platelets aggregate at the site of atherosclerotic plaque
      rupture allowing the generation of thrombin in the haemodynamic conditions which
      exist in this region.

PMID- 12500599
TI  - [Acute atherothrombotic accidents: plaque and thrombosis rupture].
AB  - The physiopathology of acute complications of atherosclerosis is more and more
      understood: it implies the initial occurrence of a mechanical accident (rupture
      or erosion of plaque) then a thrombotic reaction. The precise description of the
      mechanisms which lead to plaque vulnerability is important because it allows
      better appreciation of the risk for the patient and also allows conception of new
      therapeutic strategies.

PMID- 12500600
TI  - [Coronary thrombosis imaging in humans].
AB  - The identification of coronary thrombosis in humans has important prognostic and
      therapeutic implications. Its recognition calls for invasive techniques:
      angioscopy, coronarography, and endocoronary ultrasound. Angioscopy allows
      visualisation of the arterial surface and the detection of thrombus with great
      sensitivity. Its presence is exclusive to the acute coronary syndromes: 67% in
      unstable angina, and 75% in myocardial infarction, although it is only present in
      27% of cases of stable angina. The relative complexity of its use has led to the
      abandonment of this technique. Coronarography allows an indirect approach to
      coronary thrombosis. Certain aspects are evocative such as: intraluminal filling
      defect, complete occlusion with upstream convexity, ulceration and eccentric type
      2 Ambrose classification plaques. As a function of the clinical presentation, the
      coronarographic views allow a good specificity for the diagnosis of thrombus. The
      sensitivity is weak, however, compared to angioscopy. Endocoronary ultrasound
      does not allow identification of fresh thrombus which is not echogenic and does
      not allow differentiation between older thrombus and lipid plaque. In the future,
      magnetic resonance imaging could prove interesting in the detection of recent
      thrombus.

PMID- 12500601
TI  - [Biological markers for acute phase hemostasis in coronary thrombosis].
AB  - Associated with rheological conditions, multiple factors regarding haemostasis
      and fibrinolysis contribute to the instability and rupture of atherosclerotic
      plaque. Various biological parameters are modified during the occurrence of a
      coronary thrombotic episode, but do these increasingly identified alterations
      constitute a cause or a direct consequence of this accident? With the increasing
      identification of markers more and more sensitive but of limited specificity, the
      relative abundance of studies in the literature contrasts with the paucity of
      effective assets for everyday clinical practice. In fact, the potential use of
      these indicators in the evaluation of the pathogenesis of vascular accident,
      their eventual prognostic value, their predictive nature in therapeutic strategy,
      and their relevance for patient classification and follow up remain to be
      established on a wider scale. There is growing interest in the detection of
      evidence of cellular cooperation or a vascular compartment lesion thanks to the
      development of new diagnostic tools such as flux cytometry or immunoenzymology.
      While advances in biology have allowed undeniable clarifications of the
      physiopathology of coronary accidents and in the management of thrombotic
      pathology, it must nevertheless be endeavoured to give a practical response to
      the numerous questions where doubt remains, and to pursue the search for markers
      or tests clinically relevant.

PMID- 12500602
TI  - [Thrombosis and ischemia: experimental data].
AB  - Thrombosis and ischaemia are often linked to an atherosclerotic arterial lesion.
      An inflammatory process implicating leucocytes and inflammation mediators
      (cytokines) as well as atheroma plaque rupture liberating tissue factor are at
      the origin of this pathology. Equally, blood platelets play an important role,
      not only with the formation of platelet aggregates, but also by their
      procoagulant action resulting from the exposure of membrane phospholipids.
      Apoptotic cells release procoagulant microparticles from the plaque, favouring
      thrombogenesis. In this context reperfusion would a priori restore blood flow,
      but it is also the origin of cytotoxicity due to the sudden release of
      necrotising factors. Various animal models are used to experimentally reproduce
      arterial thrombosis either following or not following ischaemia/reperfusion.
      Among them the model of progressive coronary occlusion by intraluminal electrical
      stimulation, the model of quasi-instantaneous thrombosis by the introduction of a
      copper coil, and the model of ischaemia/reperfusion by occlusion of the left
      descending coronary for 90 minutes followed by reperfusion have been studied more
      precisely in the dog. In the rat, cerebral ischaemia followed by reperfusion has
      been provoked with occlusion of the middle cerebral artery. The studies in dogs
      show that Enoxaparine significantly reduces the formation of coronary thrombus
      induced progressively by an anodal current and potentiates the action of the
      tissular activator plasminogen (t-PA) on a recently formed thrombus. At the level
      of myocardial ischaemia. Enoxaparine reduces the extent of infarction as well as
      the neutrophil and platelet accumulation in the infarcted zone or in at risk
      zone. This effect seems to correlate with an anti-inflammatory type action
      demonstrated elsewhere in vitro with platelet/neutrophil adhesion in the presence
      of P-Selectin. In all of these studies standard heparin used under the same
      conditions proves to be inactive. In the ischaemia/reperfusion model in the dog,
      aspirin has been shown to be ineffective up to a dose of 6 mg/Kg. Enoxaparine is
      an example of a possible double anti-thrombotic and anti-ischaemic component in
      the prevention of disorders caused by the thrombosis-ischaemia-reperfusion triad.

PMID- 12500603
TI  - [Non-ST acute coronary syndromes].
AB  - Acute coronary syndromes are the first cause of death in France. Unstable angina
      is the most frequent acute coronary syndrome. Risk stratification to predict
      morbimortality and the risk of major hemorrhage is the key step of the medical
      approach. Combined antithrombotic therapy (aspirine + clopidogrel + LMWH) has led
      to a substantial reduction of major coronary events with a good tolerance because
      of the short duration of such aggressive strategy. This combined antithrombotic
      also allowed to increase the benefit of an early invasive strategy including
      coronary angiogram with stent percutaneous coronary intervention.

PMID- 12500604
TI  - [Revascularization of acute myocardial infarction. Doing better and doing more].
AB  - Effectiveness, safety, moderation, complementary, network, consensus, strategy
      and evaluation are the key words in the therapeutic management of acute
      myocardial infarction. They focus the development of pharmacological and
      interventional tools of recanalisation, and the decisions for those who use them.
      In order to cover a condition for which the patient and doctor alike choose
      neither time nor place, they lead to linking methods and disciplines together for
      a united approach. They take account of practice in order to adapt scientific
      data to the realities of exercise, to justify the given means, and to propose
      clear, realistic and useful management guidelines to first contact doctors. They
      deliver the best to the greatest number of patients.

PMID- 12500605
TI  - [Critical reading for studies on antithrombotic medications in acute coronary
      syndromes].
AB  - Numerous studies of anti-thrombotic medications in the treatment of acute
      coronary syndromes have been published in the past few years. The "technical"
      quality of these studies is usually good. However, the critical reader must focus
      on the potential use of the observed differences for his patient. In particular,
      the judgement criteria chosen and the comparator used as reference treatment must
      be examined with care. Concerning the judgement criteria, it is often combined;
      it must therefore be decided which is or are the components of these criteria
      that are favourably influenced by the treatment. Similarly the clinical relevance
      of the chosen criteria must be questioned. This leads to a discussion of the
      substitution criteria. Then the judgement criteria must reflect the risk/benefit
      ratio: however few studies include haemorrhagic risk in the judgement criteria.
      The choice of comparator reflects current practice on the one hand, and the
      necessity to standardise the control group treatment on the other. This can
      continue for several years after the publication of a study, which brings into
      question whether the result would be identical taking into account the evolution
      of current practice. Analysis of anti-thrombotic studies with reference to these
      two criteria allows recommendations to be made concerning the use of anti
      thrombotics in acute coronary syndromes.

PMID- 12500606
TI  - [Antithrombotic therapy for ischemic cerebrovascular accident].
AB  - Antithrombotic therapy should be considered in the acute phase of an ischaemic
      stroke in patients who are not candidates for thrombolysis. The recommended
      treatment is aspirin, 160 or 300 mg daily, associated in bed-ridden patients with
      prophylactic heparin therapy to avoid venous thromboembolic complications.
      Although not founded on scientific proof, high dose anticoagulants may be used
      instead of aspirin in special cases presumed to be at high risk of early
      recurrence of embolism or of extension of thrombosis. Secondary prevention in
      patients who have already suffered a non-embolic ischaemic stroke is based mainly
      on antiplatelet drugs. Aspirin, clopidogrel or the association of aspirin and
      dipyridamole are possible first the options. Ticlopidine is not recommended as
      treatment of first intention because of its secondary effects and the necessity
      of monitoring the blood count. Oral anticoagulants are not recommended after a
      non-cardio-embolic ischaemic stroke except in special cases (e.g. deficit in
      inhibitors of blood clotting). Secondary prevention in patients at high cardio
      embolic risk (e.g. atrial fibrillation) should be based on oral anticoagulants.
      Cardiac disease carrying a low or uncertain risk (e.g. patent foramen ovale
      without an atrial septal aneurysm) is usually treated with platelet inhibitors.

PMID- 12500607
TI  - [Thrombosis and antithrombotic agents in peripheral artery disease].
AB  - Aspirin remains the most useful antithrombotic agent in peripheral arterial
      disease. In intermittent claudication, there is no indication for oral
      anticoagulant except in the presence of emboligen cardiopathy (atrial
      fibrillation, valvular prosthesis). In critical leg ischemia, there is no proof
      of benefit for anticoagulation. In the prevention of distal bypass of the legs,
      the same efficacy is observed for aspirin and oral anticoagulant, but in both
      treatment occlusion remains frequent, 25% of patients after two years of follow
      up.

PMID- 12500609
TI  - Culture, anthropology, and the return of "complementary medicine".

PMID- 12500610
TI  - The growing interest of biomedicine in complementary and alternative medicine: a
      critical perspective.

PMID- 12500611
TI  - CAM differentiated.

PMID- 12500612
TI  - If CAM rose from the ashes of western holism, what now?

PMID- 12500613
TI  - Not all alternatives are complementary.

PMID- 12500614
TI  - Integrative medicine and culture: toward an anthropology of CAM.

PMID- 12500615
TI  - The sound of barking dogs: violence and terror among Salvadoran families in the
      postwar.
AB  - This article examines the transgenerational transmission of trauma among
      campensino living in a rural, repopulated community in El Salvador. Research with
      Holocaust survivors and their children has shown that traumatic symptoms can be
      transmitted to children who did not directly experience the Holocaust. The
      mechanisms by which this transgenerational transmission occurs have not been
      fully explored and require an expansion of medical and anthropological
      conceptualizations of posttraumatic illness. Through their reactions to and
      interpretations of everyday events, campesino parents who lived in the guerrilla
      camps explicitly transmit trauma to children who did not experience the recent
      civil war. Illness narratives by sufferers of nervios transmit trauma and point
      to the basic immorality of the war, an immorality that continues today. In
      addition, the symptoms of nervios constitute a mechanism by which trauma is
      implicitly transmitted. Symptoms of nervios point to what generally is not and,
      indeed, cannot be voiced: the destruction of primary relationships in the family
      and unresolved grief and helplessness, which, through the responses of family
      members to the sufferer, are reproduced and reenacted in the present family
      context.

PMID- 12500616
TI  - Why do teens smoke? American Indian and Hispanic adolescents' perspectives on
      functional values and addiction.
AB  - Tobacco use by the young is one of the greatest public health concerns in the
      United States and is targeted by a number of prevention and control programs. A
      fuller understanding of the social and cultural values that youths attach to
      smoking is important in achieving focused, effective prevention strategies.
      Drawing on data collected through individual and focus group interviews, this
      article examines reasons that Hispanic and American Indian youths give to explain
      their smoking. The analysis presented here focuses on two interrelated sets of
      reasons: the functional values of tobacco use (including mood management, peer
      influences, and image maintenance) and addiction. This article concludes with a
      discussion of the implications these data may have for prevention and cessation
      programs aimed at youth and outlines ideas for an anthropological research agenda
      on youth and tobacco.

PMID- 12500617
TI  - Articulating silences: experiential and biomedical constructions of hypertension
      symptomatology.
AB  - In this article, we explore the flexible configuration of a local knowledge
      system about hypertension symptoms, foregrounding it against prevailing
      biomedical assertions regarding the asymptomatic or "silent" nature of
      hypertension. The complex and coherent knowledge system held by older African
      Americans living in a southern, rural community stands in contrast to the current
      scientific discourse and local biomedical perspectives on hypertension
      symptomatology. The older African American participants in this study apply local
      knowledge of hypertension symptomatology to make health decisions nearly every
      day. Despite this, most biomedical practitioners maintain a distance from these
      lay sources of knowledge, often remaining stalwart in their refusal to recognize
      the existence or influence of symptoms. We conclude that authoritative knowledge
      ultimately lies in the minds and bodies of the elders, who have encountered
      symptoms as guideposts that direct action, rather than with a biomedical
      "reality" that is yet unresolved.

PMID- 12500618
TI  - Managed care or managed inequality? A call for critiques of market-based
      medicine.
AB  - This review article critiques the growing dominance of market-based medicine in
      the United States against the background of existing problems with quality of
      care, rising costs, devaluation of doctor-patient relationships, and, especially,
      persistent inequalities of access and outcomes. It summarizes the present state
      of health care delivery by focusing on the concurrent trends of growth in managed
      care, expanding profits, increasing proportion of those uninsured, and widening
      racial, ethnic, and class disparities in access to care. Allowing market forces
      to dictate the shape of health care delivery in this country ensures that
      inequalities will continue to grow and modern medicine will become increasingly
      adept at managing inequality rather than managing (providing) care. The article
      challenges anthropology to become more involved in critiquing these developments
      and suggests how anthropologists can expand on and contextualize debates
      surrounding the market's role in medicine, here and abroad.

PMID- 12500619
TI  - [Congenital heart disease in the adult].

PMID- 12500620
TI  - [Surgical treatment ot congenital heart disease].
AB  - Congenital heart disease is a heterogeneous group of intra- and extra-cardiac
      abnormalities of very variable prognosis, which have been classified according to
      their structural and functional consequences. The functional abnormalities are
      mainly centered on variations of pulmonary arterial flow that can generally be
      managed by simple palliative procedures. The extra-cardiac abnormalities affect
      preferentially the aorta. They may be embryonic vascular remnants responsible for
      tracheo-bronchial compression or obstructive lesions which are amenable to
      different types of vascular reconstruction procedures. These anomalies may be
      isolated or form part of a more complex malformative syndrome. Complete repair
      may be possible using techniques adapted to the main structural abnormalities of
      the cardiac architecture: reconstruction of the atrial or ventricular septa,
      restoration of the ventricular outflow tracts and redirection of blood flow
      within the atria. Among the therapeutic motivations developed for complete repair
      over the last decade, reconstruction of the pulmonary arteries by unifocalisation
      and Ross' procedure for left ventricular outflow tract abnormalities deserve
      special mention; in addition, a major therapeutic principle has been established
      for repair of ventriculoatrial malposition and discordance: the re-connection of
      the aorta with the left ventricle.

PMID- 12500621
TI  - [Surgery for congenital heart disease in the adult: characteristics].
AB  - Surgery for congenital cardiopathy in adulthood presents at least four
      distinctive characteristics: rarity (less than 1% of all cardiac surgical
      procedures), extreme diversity of anatomo-clinical situations, the customary
      multivisceral disorder (pulmonary in particular) and certain specific technical
      differences (concerning the conduction of extracorporeal circulation and the
      surgical procedure itself). Because of these features, the operative indications
      are difficult to define in this population. They must be decided case by case,
      arriving at a well-tuned equilibrium between exaggerated intervention and
      excessive expectancy. Such an objective has the most chance of being realised in
      a specialised medico-surgical team.

PMID- 12500622
TI  - [Interventional catheterization in congenital heart disease in the adult].
AB  - Interventional catheterisation comprises performing a palliative or curative
      procedure during arterial or venous cardiac catheterisation. This procedure can
      be performed at any age, equally well in the newborn or adults affected by
      congenital cardiopathy: in order to definitively treat a congenital cardiopathy,
      unrecognised in infancy but diagnosed in adulthood, such as pulmonary valvular
      stenosis, coarctation of the aorta, persistent ductus arteriosus, ostium secundum
      type interatrial communication, coronaro-cardiac fistula, pulmonary arterio
      venous fistula, and patent foramen ovale; in order to improve the haemodynamic
      state of a complex congenital cardiopathy, for example by creating an interatrial
      communication, or by opening the pulmonary route in a complex cardiopathy which
      cannot be completely repaired; in order to complete a surgical procedure, to
      treat recurrence of peripheral pulmonary stenosis or recurrence of coarctation,
      and to embolise the systemic vessels leading off the aorta or veno-venous
      anastomoses after cavopulmonary intervention. Paediatric cardiology can lead to
      occlusion of a left-right or right-left shunt with different devices, alleviation
      of an arterial or venous valvular stenosis with dilatation catheters, or
      implantation of endoprostheses in arterial or venous stenoses.

PMID- 12500623
TI  - [Arrhythmias after surgery for congenital heart disease].
AB  - The improvement of surgical techniques over the last few years have made
      postoperative chronotropic insufficiency either by sinus node dysfunction or
      iatrogenic atrioventricular block less common. However, reentrant tachycardia
      around lines of incision or a patch may be observed. Persistent dilatation of a
      cardiac chamber or ventricular dysfunction are predisposing factors. Flutter-like
      arrhythmias occur mainly after atrial surgery (closure of atrial septal defects,
      Mustard, Senning or Fontan procedures). Ventricular tachycardias are observed
      more often after correction of tetralogy of Fallot or in patients with severe
      ventricular dysfunction. In fact, any type of arrhythmia may arise, especially
      when the lesion is operated late in childhood or in adulthood with a partial
      haemodynamic result (residual gradient, valvular regurgitation or ventricular
      dysfunction...). In this context, regular ECG follow-up should be associated with
      repeated Holter monitoring and exercise stress testing. From the therapeutic
      point of view, amiodarone remains the best antiarrhythmic drug. Radiofrequency
      ablation techniques represent a recent but decisive advance in the management of
      atrial arrhythmias.

PMID- 12500624
TI  - [Pregnancy and congenital heart disease].
AB  - Congenital cardiopathies currently represent the majority of cardiac anomalies
      observed during pregnancy. The latter leads to significant haemodynamic
      modifications which can sometimes be poorly tolerated in the case of severe
      cardiopathy. However, as a rule pregnancy is generally well supported if the
      functional state of the patient beforehand is satisfactory (class I or II of the
      NYHA). The type of cardiopathy also plays a role. Left-right shunts tolerate
      pregnancy well in most cases. On the other hand severe aortic stenoses expose
      serious complications. Above all it is the cyanogenic cardiopathies which are
      poorly tolerated by the mother and the fetus, and more so the lower the oxygen
      saturation. Eisenmenger's syndrome causes a major risk to life for the young
      mother and is a formal contra-indication to pregnancy, as is pulmonary arterial
      hypertension. Patients with a Fontan anastomosis or an intra-atrial repair of
      transposition of the great vessels can support pregnancy very well if the
      systemic ventricle has good function. In Marfan's syndrome the aortic diameter is
      the essential prognostic element. In most congenital cardiopathies pregnancy
      nevertheless has a favourable outcome for the mother and infant. Vaginal delivery
      should be the rule. A close cardio-obstetric collaboration is the principal
      condition to allow the young cardiac female to well endure a pregnancy.

PMID- 12500625
TI  - [Sports and congenital heart disease in the adult].
AB  - The practice of sporting activities is not only allowed, but also should be
      recommended for most adult patients affected by congenital cardiopathy. This
      permissive attitude should be based on a good understanding of congenital
      cardiopathy, whether operated or not, and its foreseeable evolution in adulthood.
      Aptitude for sport should be supported by a precise evaluation of the patient's
      functional, rhythmological and haemodynamic status at rest and under effort.
      Regular monitoring is often justified, and is greatly facilitated by the quantity
      and quality of modern non-invasive surveillance methods, the first of which are
      Doppler echocardiography and ergometric techniques. The stress test should be
      readily coupled with a study of ventilatory parameters under effort, as there are
      frequently disturbances of pulmonary exchange. Non-competitive sporting activity
      is generally implied for congenital cardiac patients, but there are exceptions in
      certain cases. Patients should generally be directed towards an endurance sport,
      undertaken without any spirit of competition, as a function of the results from
      effort tests (easy confrontation for this type of sport). It is only based on the
      tolerance of this basal activity that other sports are then authorized. It is
      illusory to demand systematisation for sporting aptitude in each type of
      cardiopathy as the situations encountered in practice vary from one individual to
      another. It is nevertheless possible to define a certain number of guidelines
      which are suitable for modification for each patient as a function of the
      clinical history, any associated vascular risk factors, and the patient's
      motivation. All said and done, absolute contra-indications to sport are rare.
      Relative contraindications to a type of sport or to a level of sporting activity
      as a function of the cardiopathy are encountered more and more. Nowadays the
      selective aptitude for certain sports should be discussed rather than the contra
      indications. Under these conditions, sport can only be beneficial for adult
      congenital cardiac patients, and it plays a part in the prevention of the
      acquired risk of cardiopathy from which these patients have no escape.

PMID- 12500626
TI  - [Endocarditis and congenital heart disease in the adult].
AB  - The prevalence of congenital cardiopathy is approximately 8% of live births, and
      80 to 85% of patients reach adulthood thanks to the progress in the management of
      even complex malformations. Congenital cardiopathies represent 10 to 18% of
      adulthood cardiopathies complicated by infectious endocarditis, and in the
      specialist units for adolescent and adult congenital cardiac patients, 5% of
      admissions are provoked by endocarditis. The majority of malformations have a
      risk of infected graft, but patients who have a complex cyanogenic cardiopathy or
      an operated cardiopathy requiring insertion of prosthetic material, and those who
      have already had previous episodes of endocarditis are at a very high risk.
      Longitudinal studies show evolution of the responsible microbes, with an increase
      of the HACEK group; nevertheless, the streptococci and staphylococci remain
      uppermost. Diagnosis relies on the classic Duke University criteria but Doppler
      echocardiography is sometimes difficult to interpret in complex malformations or
      extra-cardiac sites of infection, and in 6 to 11% of cases the microbe is not
      identified. Infectious endocarditis remains a particularly serious complication:
      50% of patients have aggravation of their cardiopathy and 20 to 30% require
      surgery; however the mortality has fallen by 20% to a little less than 5% in the
      most recent series. It is vital that patient education should be pursued even if,
      in certain circumstances, prophylaxis is not always either possible or
      effective....

PMID- 12500627
TI  - [Social problems and rehabilitation of operated or unoperated adults with
      congenital heart disease].
AB  - Advances in surgical management have enabled a large number of children with
      cardiac malformations, even very severe lesions, to reach adulthood. Besides the
      purely medical problems which may persist, difficulties in social and
      professional integration may alter their quality of life and raise doubts about
      the utility of treatment. It is necessary to assess the symptoms, the causes and
      therapeutic options available, as if this situation was a true illness. The
      quality and precocity of surgical techniques make the outcomes more optimistic in
      adulthood, but those patients now over 30 years of age have difficulties in
      founding a family and do not enjoy the same chances of training as the rest of
      the population, even though they may get more acceptable jobs than in previous
      years. To this end, legislative help may be useful in the most difficult cases.

PMID- 12500628
TI  - [Atrial septal defects: problems in adults].
AB  - The clinical features of atrial septal defects in adults have changed due to the
      generalisation of surgery of the anomaly in childhood and the widespread use of
      transoesophageal echocardiography. Rare complications, such as paradoxical
      embolism or cerebral abscess, can now be more reliably attributed. Pulmonary
      hypertension, a feared traditional complication, is better understood: the severe
      form with right-to-left shunting (Eisen-menger's syndrome) occurs rarely in young
      adults, with a probable genetic predisposition; the less severe form, with
      persistence of a large left-to-right shunt is observed more often in adults over
      50 years of age, and closure of the atrial septal defect remains beneficial over
      a long period of time. It has now been shown that this repair, even when
      performed late, improves symptoms but with less effect on atrial arrhythmias.
      Percutaneous closure is the treatment of choice and surgery is only considered
      after failure of endocavitary closure. The indication for closure of small atrial
      septal defects remains the subject of controversy.

PMID- 12500629
TI  - [Ventricular septal defects in the adult].
AB  - Ventricular septal defects (VSD) are very common in children but much rarer in
      adults because the majority either close spontaneously or are operated. The
      persistent VSD are usually membranous with a small or moderate shunt without
      pulmonary hypertension. They are usually well tolerated clinically but are at
      risk of complications, mainly bacterial endocarditis and aortic regurgitation.
      Doppler echocardiography plays a leading part in diagnosing the site and
      evaluating the left-to-right shunt and its complications. Surgery may be
      indicated in cases of large left-to-right shunt (QP/QS > 2) and when there are
      complications. Patients operated for VSD in childhood are usually considered to
      be cured. However, anatomical, haemodynamic, functional, electric and
      echocardiographic abnormalities may persist, justifying long-term cardiological
      follow-up.

PMID- 12500630
TI  - [Operated and unoperated coarctation of the aorta in the adult].
AB  - The common denominator of patients operated for isthmic coarctation of the aorta
      in childhood who reach adulthood, is the risk of hypertension which is observed
      in about 70% of cases with its cortege of cerebral and coronary vascular
      complications or left ventricular hypertrophy, which considerably reduce life
      expectancy. Systematic follow-up of these patients includes, in addition to
      clinical and echocardiographic examination, three essential investigations:
      exercise stress testing, the study of arterial mechanics and angio MRI.
      Hypertension on exercise is observed in 70% of patients of whom 21% have critical
      hypertension despite excellent anatomical correction. Vascular study shows
      changes in arterial eactivity and endothelial function independent of the age at
      operation: MRI often demonstrates aortic irregularities which partially explain
      the hypertension. Three therapeutic choices are available: in cases of
      restenosis, balloon angioplasty with or without stenting gives good results: when
      hypoplasia of the aorta is observed, a surgical repair is recommended: otherwise,
      pharmacological treatment with life style adaptation including carefully managed
      physical exercise is appropriate. Coarctation diagnosed in adulthood is rare but
      poses special problems. Treatment by angioplasty is possible but is complicated
      by aneurysms of the isthmus in 20% of cases so that nowadays surgery is the
      treatment of choice. This is difficult and dangerous because of the collateral
      circulation, the fragility of the aorta and the risk of medullary ischaemia.
      Resection-anastomosis is the most effective technique with or without
      cardiopulmonary bypass, reducing the hypertension in 70% of cases.

PMID- 12500631
TI  - [Congenital aortic stenosis in the adult].
AB  - Congenital aortic stenosis is a common pathology in adults. The valvular lesion,
      usually secondary to a bicuspid valve, is dominant. Dilatation of the ascending
      aorta, the result of a jet lesion or structural wall abnormalities, is often
      observed in association with the valvular stenosis. Subvalvular stenosis is
      progressive and may only present late, after surgery of another congenital
      lesion. Supravalvular stenosis is much less common and is usually diagnosed in a
      dysgenetic context. Echocardiography is usually diagnostic and enables
      quantification of the stenosis and evaluation of secondary left ventricular
      changes. Exercise stress testing is decisional in asymptomatic severe stenosis.
      Percutaneous valvuloplasty is a good palliative procedure. Other surgical
      techniques comprise valvular commissurotomy, supravalvular valvuloplasty,
      valvular replacement (autograft, homo- or heterograft or mechanical prostheses).
      The indications depend on the quantification of the stenosis, symptoms, the
      results of exercise testing, the valvular lesion secondary to subaortic stenosis
      and the progression of the aneurysm of the ascending aorta.

PMID- 12500632
TI  - [Cyanotic heart disease in the adult].
AB  - Patients with cyanotic heart disease may have an acceptable quality of life but
      are exposed to several complications: polycythaemia, often beneficial but with
      its risks: hyperviscosity, hyperuricaemia, thrombocytopaenia, blood clotting
      abnormalities; and the other complications of right-to-left shunt: cerebral
      abscess, cerebral embolism, endocarditis. The hypoxia may be improved by
      interventional catheterisation or palliative surgery. The Eisenmenger syndrome is
      life-threatening in pregnancy or during general anaesthesia. These patients are
      at risk and sometimes have iatrogenic complications, so usual cardiological
      treatment may be dangerous: diuretics, ACE inhibitors, oral anticoagulants,
      antiarrhythmics.

PMID- 12500633
TI  - [Ebstein's anomaly].
AB  - Since Ebstein's first description in 1866 and the first surgical attempts at
      treatment in the 1950's, the natural history of this condition remains obscure.
      The anatomical description contrasts with the clinical and prognostic variability
      of this malformation. The form observed in the foetal or prenatal periods has a
      very different prognosis to that observed in adults. The risk factors are not the
      same even though the anatomical entity is comparable. The difficulty in managing
      these patients is due to the problems of diagnosis and determination of these
      prognostic factors. Advances in echocardiography, the key investigation which
      facilitates diagnosis, and in surgical and ablation techniques, have improved our
      understanding of this condition and its prognosis.

PMID- 12500634
TI  - [Outcome of operated Fallot's tetralogy].
AB  - Fifty years after the beginning of cardiac surgery, a large percentage of
      operated congenital heart disease patients attain adulthood. The tetralogy of
      Fallot is one of the malformations in which the natural outcome was unfortunately
      nearly fatal in the long-term. Open heart surgery has radically transformed the
      prognosis of this, the most common of all cyanotic congenital cardiac
      malformations. Nowadays, most operated patients lead normal professional and
      family lives. Lonf-term survival after correction is between 90-95% after 30-35
      years. Although surgical repair is satisfactory, the operated heart is not
      anatomically normal. The patients have a variable degree of devalvulation of the
      pulmonary outflow tract, a scar on the right ventricle, a patch repairing the
      ventricular septal defect and scars on the atrium (cannulation for
      cardiopulmonary bypass). These sequellae expose the patients to a number of
      complications, notably arrhythmic and sometimes haemodynamic, affecting the right
      ventricle. The late mortality rate varies from 5 to 13% in the literature. The
      main causes of death are sudden death and reoperation. Sudden death is the most
      severe long-term complication but it is uncommon, affecting less than 5% of the
      population. It is mainly due to ventricular arrhythmias. Certain predisposing
      factors should be identified during long-term follow-up, among them the presence
      of haemodynamic abnormalities: systolic overload (residual pulmonary stenosis) or
      diastolic overload of the right ventricle (pulmonary regurgitation), infundibular
      aneurysm, right ventricular dysfunction. It would appear to be important to
      prevent pulmonary regurgitation by preserving the pulmonary valve even if it
      means persistence of a mild transvalvular pressure gradient. When pulmonary
      regurgitation is inevitable, follow-up is essential to evaluate the timing of
      valvulation of the pulmonary orifice. Despite these different complications which
      must be understood for proper follow-up of these patients, the long-term outcome
      of operated tetralogy of Fallot remains very good.

PMID- 12500635
TI  - [Outcome of operated transposition of the great vessels].
AB  - The object of this report is to describe the long-term outcome of patients
      operated for transposition of the great vessels. Understanding what we mean by
      transposition of the great vessels, the surgical options with their advantages,
      limitations and complications, helps the cardiologist decide on the mode of
      follow-up, the investigations and even the reoperations that these patients may
      need. The authors review the results of the literature and their experience over
      the years with children and adults with congenital heart disease. Although
      considerable progress has been made in the management of a condition considered
      to be constantly and often rapidly fatal, most of the procedures which allow
      patients to have a normal or quasi-normal quality of life have not resolved all
      the problems and require maintenance of long-term follow-up.

PMID- 12500636
TI  - [Followup of adults with a Fontan-type cavopulmonary derivation].
AB  - The Fontan procedure is a technique used in single ventricle syndromes and
      initiates a circulation which bypasses the right ventricle. It was described by
      Fontan in 1971. Many variations of this operation have been described and
      classified under the term of total cavopulmonary derivation. These operations
      result on long-term functional benefit. However, the 15 year survival rate is
      only 55 to 80%. This procedure (often carried out in childhood) is considered to
      be palliative rather than curative. The mortality is due to long-term
      complications, the frequency of which increases with the length of follow-up of
      the patient. The causes are: the Fontan circulation itself (arrhythmias,
      thrombosis, inferior caval stasis (hepatic, exsudative enteropathy), recurrence
      of cyanosis): the underlying cardiac disease (ventricular failure,
      atrioventricular valvular regurgitation); other complications (endocarditis and
      extracardiac, in particular orthopedic problems). Any of these complications may
      be an indication for cardiac transplantation, a high risk procedure because of
      previous multiple surgical interventions.

PMID- 12500637
TI  - Maya Angelou. Humanitarian extraordinary + greatest living American poet.
AB  - Maya Angelou is testimony to the resilience of the human spirit. Rising above
      poverty and abuse to become one of the 100 best writers of the 20th century, she
      has used her extraordinary talents to crusade against injustice and prejudice.
      She measures her success by her ability to love and to care for others.

PMID- 12500638
TI  - Dawn Degenhardt. The first lady of adoption: premier advocate for children.
AB  - Dawn Degenhardt has always had an incredible love for children and believes that
      they deserve a family no matter how special their needs. She has found homes for
      over 3,000 children over the last 25 years. Her international program not only
      facilitates adoptions but also offers humanitarian aid to orphanages and
      families. Her work restores our faith in humanity.

PMID- 12500639
TI  - Debi Faris. Bringing dignity to children in life + in death.
AB  - Debi Faris founded Garden of Angels so that innocent babies left to die on
      roadways and in trash bins are treated with value and dignity. She gives them a
      proper burial service, celebrating their brief lives, and provides a final
      resting place to honor their memories. Debi Faris is active in the legislative
      and educational process and is instrumental in passing new laws that save the
      lives of newborns.

PMID- 12500640
TI  - C. Scott Harrison, MD. Healing bodies + souls.
AB  - C. Scott Harrison, an orthopedic surgeon, discovered a need for his services
      while serving a humanitarian mission in Africa. As a witness to the deplorable
      treatment of children with deformities, he founded Crippled Children's United
      Rehabilitation Effort International (CURE) and has successfully operated on
      thousands of children. Dr. Harrison has built three hospitals in third world
      nations and is in the process of completing the fourth.

PMID- 12500641
TI  - Noel Irwin Hentschel. The first lady of caring: helping people to help
      themselves.
AB  - Noel Irwin Hentschel, CEO of American Tours International, found her inspiration
      to "help those most in need to help themselves" at a conference addressed by
      Mother Teresa. This meeting inspired her to establish the Noel Foundation, whose
      mission is to provide education, job training, and health care on an
      international basis.

PMID- 12500642
TI  - Kenneth Maryboy. Answering the dreams, wishes, + needs of Native Americans.
AB  - Kenneth Maryboy, a representative of the Navajo Tribal Council and medicine man,
      serves as a living bridge between the old ways of the Navajo and the current
      realities of life in America. He adapted the Western notion of Santa Claus to
      meet the continuing needs of the poorest Native Americans living in remote areas
      of Utah and Arizona.

PMID- 12500643
TI  - Paul Newman. The king of entrepreneurial philanthropy.
AB  - Paul Newman is a world-class actor, producer, director, and philanthropist. He
      launched a revolutionary enterprise, Newman's Own, where the profits generated
      from the sale of its products benefit various public charities. He also founded
      the Hole in the Wall Gang Camp for children with life-threatening illnesses. He
      has used his talents, fame, and resources to become a stellar example of
      entrepreneurial philanthropy.

PMID- 12500644
TI  - Nancy Rivard. The color of   love.
AB  - Nancy Rivard's personal journey to be a part of something bigger than herself
      resulted in the founding of Airline Ambassadors International (AAI). As a flight
      attendant for American Airlines, she enrolled the industry through a large-scale
      volunteer effort and established Airline Ambassadors, whose programs have
      delivered school supplies, food, medicine, and medical supplies to upwards of
      100,000 children in 25 nations.

PMID- 12500645
TI  - Judy Schwank. Healing the body + soul of children.
AB  - Judy Schwank, a nurse, attorney, and child advocate, has facilitated the effort
      to bring thousands of ill children from Guatemala into the United States for
      treatment and surgery. She has founded two non-governmental organizations, most
      recently Children's Aid Mission International (CAMI), whose mission involves
      health care, education, and social advocacy.

PMID- 12500646
TI  - Introducing our 2002 Caring Institute Young Adult Winners.

PMID- 12500647
TI  - A tribute to Dorothy Height. Crusader for human rights.
AB  - Dorothy Height, is a legendary figure in the American civil rights movement and
      in the broader worldwide human rights movement. As President of the National
      Council of Negro Women (NCNW), she worked tirelessly toward the enactment of
      civil rights and for equal rights in education, housing, and employment.

PMID- 12500648
TI  - Working smarter or harder?

PMID- 12500649
TI  - Quality control circles in the Veterans Administration hospital.
AB  - In response to residents' reports of inefficiencies in the Veterans
      Administration (VA) system, a temporary task force of quality control circles was
      implemented at a VA hospital. A total of 25 internal medicine residents, on
      rotation at the VA, were subdivided into four groups. Each group was presented
      with a different problem, given the components and constraints of the problem,
      and asked to identify possible solutions. Program results were submitted to the
      hospital administration. Efforts are now being made to improve the working
      environment for medical residents.

PMID- 12500650
TI  - The impact of the Balanced Budget Act of 1997 on Medicare in the USA: the fallout
      continues.
AB  - Although the United States Congress has attempted to ameliorate some of the
      adverse impacts of the Balanced Budget Act through the 1999 Balanced Budget
      Refinement Act, the final results of the reforms to Medicare remain to be seen.
      This article provides an update and examines the impacts of the Balanced Budget
      Act on health providers and medical education. The authors also discuss the
      implications of these impacts for further policy adjustment.

PMID- 12500651
TI  - Transforming a run down general practice into a leading edge primary care
      organisation with the help of the EFQM excellence model.
AB  - This article explains how a primary care team transformed a run down general
      practice into a leading edge healthcare organisation by adopting the principles
      of the EFQM excellence model. The decisions surrounding the choice of approach,
      challenges faced, benefits achieved and lessons learned are all described in such
      a way that the reader may appreciate the issues which faced the members of the 15
      man team. In particular, the practice team found that describing indicators of
      quality and gathering evidence to test out assumptions regarding performance were
      vital elements in the pursuit of a continuous improvement culture that was to
      benefit patients, staff and key stakeholders alike. Whilst an increase in
      workload was experienced in the early days, the knowledge that this was
      associated with improved performance made the efforts worthwhile and the team
      eager to adopt a regular, never-ending cycle of self-assessment and improvement.

PMID- 12500652
TI  - An empirical investigation of the effectiveness of contemporary managerial
      philosophies in a hospital operational setting.
AB  - The new realities of the healthcare marketplace are forcing healthcare decision
      makers to implement innovative operational philosophies, techniques, and tools
      that were proven in other industries to enhance the effectiveness of their
      organization. This study examines the acceptance and effectiveness of these
      philosophies, techniques, and tools in a hospital operational setting. The impact
      of implementation on operational and strategic outcomes is examined for 108
      hospitals. Overall, the results of this study appear to indicate that certain
      quality improvement philosophies, techniques, and tools have been successful when
      applied in a hospital operational setting.

PMID- 12500653
TI  - Assessment of facilities management process capability: a NHS facilities case
      study.
AB  - Describes a process to assess facilities management (FM) process capabilities:
      the structured process improvement for construction environments--facilities
      management (SPICE FM) approach. The SPICE FM framework is a method that FM
      organizations can use to monitor continuously and subsequently improve their
      performance. The SPICE FM framework is being tested in a series of case studies
      to ensure that its outputs are appropriate to the FM sector and of value in the
      real world. Documents the outcomes of a study undertaken at a facilities
      directorate of a healthcare NHS trust, in searching its applicability within the
      NHS. Further describes the study methodology and the key activities undertaken
      and reviews the key communication and management processes that are in place to
      support the implementation of the strategic FM objectives within the specific NHS
      facilities directorate.

PMID- 12500654
TI  - Producing useful research about quality improvement.
AB  - Many quality improvement interventions such as educational programmes, hospital
      quality strategies, and quality evaluation systems have not been evaluated. The
      aim of this paper is to encourage research into these "quality improvement
      processes" by presenting suitable designs and methods, and by describing research
      approaches which are less familiar in healthcare. The paper proposes that the
      choice of research design depends on the level and complexity of the
      intervention. Theory-building approaches are more suitable than experimental
      theory testing approaches for evaluating higher-level complex interventions and
      for understanding critical context factors. Collaborative action evaluation
      studies can provide useful information for decision makers--an examples is given.
      "User focused" research can provide knowledge for developing more effective
      quality intervention processes and for making better decisions about their use
      and implementation.

PMID- 12500655
TI  - The RAF method for regulation, assessment, follow-up and continuous improvement
      of quality of care: conceptual framework.
AB  - The RAF method for regulation, assessment, follow-up and continuous improvement
      of quality of care was developed in Israel in the late 1980s by the Quality of
      Care Unit at the JDC-Brookdale Institute. During the past decade the RAF method
      has been adapted to and implemented successfully in a number of government
      regulatory systems operated by services in the Ministry of Health and the
      Ministry of Labor. This article presents the conceptual framework of the RAF
      method. It describes the three theoretical approaches that have been integrated-
      the tracer approach, the model for quality assurance and the introduction of
      organizational change--to create a broad conceptual framework. It then presents
      the key operational principles at work in the field that drive the RAF mechanism
      in its efforts to achieve a constant improvement in quality of care.

PMID- 12500656
TI  - The RAF method for regulation, assessment, follow-up and continuous improvement
      of quality of care: implementation in regulatory systems of government services
      and care facilities.
AB  - The RAF method for regulation, assessment, follow-up and continuous improvement
      of quality of care was developed in Israel in the late 1980s by the Quality of
      Care Unit at the JDC-Brookdale Institute. The goal of the RAF method is to
      continuously increase the level of quality of organizations providing any kind of
      a service. This article presents the developmental processes for the method's
      adaptation to a specific regulatory service--its structuring, implementation and
      assimilation--based on our experience in developing and implementing the RAF
      method in Israel. It describes how the RAF method encourages the development of
      reliable data bases, adaptation of the organizational structure, and introduction
      of a positive ideology that together promote changes leading to continuous
      improvement in quality of care.

PMID- 12500657
TI  - Health professionals' perceptions of breaking bad news.
AB  - The growth of the "patient-centred" approach to health care has highlighted the
      importance of quality communication practices. One area that remains problematic,
      however, is the process of breaking bad new to patients and/or relatives. Hence,
      there have been calls for more research and training in this domain. Reports the
      findings of a study that used the critical incident technique to explore the
      breaking bad news encounter from the perspective of the health care practitioner.
      In total 33 senior medical and nursing staff reported on situations in which they
      described specific, vividly recalled, experiences of both "effective" and
      "ineffective" bad news delivery. These reported incidents were content analysed
      and a range of key dimensions was identified for both effective and ineffective
      experiences. Interpersonal communication skills emerged as particularly salient
      factors and these are discussed in detail, together with implications for future
      research and training.

PMID- 12500658
TI  - Zinc in CCl4 toxicity.
AB  - OBJECTIVE: To investigate the protective effect of zinc in CCl4-induced
      hepatotoxicity. METHODS: Rats were treated with zinc acetate for four days. The
      zinc doses were 5 mg Zn/kg and 10 mg Zn/kg body weight respectively. Two groups
      of the zinc acetate-treated rats were later challenged with a single dose of CCl4
      (1.5 mL/kg body weight). RESULTS: Compared to control animals, the plasma of rats
      treated with CCl4 showed hyperbilirubinaemia, hypoglycaemia, hypercreatinaemia
      and hypoproteinaemia. When the animals were however supplemented with zinc in
      form of zinc acetate before being dosed with CCl4, the 5 mg Zn/kg body weight of
      zinc acetate reversed the hypoproteinaemia induced by CCl4, whereas the 10 mg
      Zn/kg body weight of zinc acetate reversed the hypoglycaemia, hyperbilirubinaemia
      and hypercreatinaemia induced by CCl4. CONCLUSION: The 10 mg Zn/kg body weight of
      zinc acetate is more consistent in protecting against CCl4 hepatotoxicity. The
      possible mechanisms of protection are highlighted.

PMID- 12500659
TI  - Effect of micronutrient supplementation on the growth of preschool children in
      China.
AB  - OBJECTIVE: To study the relationship between micronutrient supplementation and
      children growth. METHODS: A double-blind, placebo-controlled trial was conducted
      in 156 growth retarded preschool children. They were randomly assigned to five
      groups: supplemental control (S-control, n = 28), zinc supplementation (+Zn, 3.5
      mg Zn/day, n = 34), zinc and calcium supplementation (+ZnCa, 3.5 mg Zn + 250 mg
      Ca/day, n = 37), zinc and calcium and vitamin A supplementation (+ZnCaVA, 3.5 mg
      Zn + 250 mg Ca + 200 g VA/day, n = 28), Calcium, and vitamin A supplementation
      (+CaVA, 250 mg Ca + 200 g VA/day, n = 29). Another 34 children with normal height
      were selected as normal control (N-control). Supplementation continued for twelve
      months. RESULTS: The height gain in +Zn group (7.84 cm per year) and +ZnCa group
      (7.70 cm per year) was significantly higher than that in S-control group (6.74 cm
      per year, P < 0.05); The weight gain in +ZnCaVA group (2.55 kg per year) and
      +CaVA group (2.57 kg per year) was also significantly higher than that in S
      control group (2.19 kg per year, P < 0.05); The average days of illness in each
      supplementation group were lower than that in S-control (13 days per year
      compared with 23 days per year). No significant difference was observed on bone
      age. CONCLUSION: Zinc and Zinc + Calcium supplementation can improve the height
      gain, and vitamin A can improve weight gain in growth retarded preschool
      children, but do not affect the maturity of bone. Micronutrient supplementation
      can lower the morbidity of these children.

PMID- 12500660
TI  - Randomized terminal linker-dependent PCR: a versatile and sensitive method for
      detection of DNA damage.
AB  - OBJECTIVE: To design and develop a novel, sensitive and versatile method for in
      vivo foot printing and studies of DNA damage, such as DNA adducts and strand
      breaks. METHODS: Starting with mammalian genomic DNA, single-stranded products
      were made by repeated primer extension, these products were ligated to a double
      stranded linker having a randomized 3' overhang, and used for PCR. DNA breaks in
      p53 gene produced by restriction endonuclease AfaI were detected by using this
      new method followed by Southern hybridization with DIG-labeled probe. RESULTS:
      This randomized terminal linker-dependent PCR (RDPCR) method could generate band
      signals many-fold stronger than conventional ligation-mediated PCR (LMPCR), and
      it was more rapid, convenient and accurate than the terminal transferase
      dependent PCR (TDPCR). CONCLUSION: DNA strand breakage can be detected
      sensitively in the gene level by RDPCR. Any lesion that blocks primer extension
      should be detectable.

PMID- 12500661
TI  - Impact of long-term exposure to air particulate matter on life expectancy and
      survival rate of Shanghai residents.
AB  - OBJECTIVE: To evaluate the impact of long-term air particulate matter exposure on
      the life expectancy and survival rate of Shanghai residents. METHODS:
      Epidemiology--based exposure-response function was used for the calculation of
      attributable deaths to air particulate matter in Shanghai, and the effect of long
      term exposure to particulate matter on life expectancy and survival rate was
      estimated using the life table of Shanghai residents in 1999. RESULTS: It was
      shown that in 1999, the long-term air particulate matter exposure caused 1.34
      1.69 years reduction of life expectancy and a decrease of survival rate for each
      age group of Shanghai residents. CONCLUSION: The effect of long-term exposure to
      air particulate matter on life expectancy is substantial in Shanghai.

PMID- 12500662
TI  - Silica induced early fibrogenic reaction in lung of mice ameliorated by
      Nyctanthes arbortristis extract.
AB  - OBJECTIVE: To investigate the pharmacological effect of Nyctanthes arbortristis
      (NAT) leaf extract in the prevention of lung injury induced by silica particles.
      METHOD: Lung injury was induced in Swiss mice through inhalation exposure to
      silica particles (< 5 mu) using a Flow Past Nose Only Inhalation Chamber at the
      rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL)
      fluid collected between 48 and 72 h was subjected to protein profiling by
      electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung
      histopathology was performed to evaluate lung injury. RESULTS: Inhalation of
      silica increased the level of tumor necrosis factor-alpha (TNF-alpha), and of the
      66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control.
      Pre-treatment of silica exposed mice with NAT leaf extract significantly
      prevented the accumulation of TNF-alpha in the BAL fluid, but the 66 and 63 kDa
      peptides remained unchanged. The extract was also effective in the prevention of
      silica-induced early fibrogenic reactions like congestion, edema and infiltration
      of nucleated cells in the interstitial alveolar spaces, and thickening of
      alveolar septa in mouse lung. CONCLUSION: NAT leaf extract helps in bypassing
      silica induced initial lung injury in mice.

PMID- 12500663
TI  - Redifferentiation of human gastric cancer cells induced by ascorbic acid and
      sodium selenite.
AB  - OBJECTIVE: To explore the effects and mechanisms of ascorbic acid (AA) and sodium
      selenite (SS) on growth inhibition and redifferentiation in human gastric cancer
      cells. METHODS: In the present study, trypan blue dye exclusion method was used
      to determine the cell growth curve and mitotic index, cell electrophoresis and
      colonogenic potential were used as the indexes of redifferentiation. In order to
      find out the mechanisms of redifferentiation, the activities of superoxide
      dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed,
      the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were
      evaluated. RESULTS: After treatment with AA 3 mol/L + SS 2 mu mol/L, the growth
      rate and mitotic index of human gastric cancer cells (MGc-803) decreased
      remarkably. The indexes related with cell malignancy were alleviated. For
      example, cell surface charge was obviously decreased, the electrophoresis rate
      was dropped from 2.21 to 1.15 mu m.s-1.V-1.cm-1. The indexes related with cell
      redifferentiation were promoted. For example, the colonogenic potential was
      decreased to 93.5%. These results indicated that redifferentiation of human
      gastric cancer cells was successfully induced by AA + SS. The activities of SOD
      and GPX were significantly higher, while the activity of CAT was slower in
      treated group than that in the control. The content of MDA was slightly
      decreased, GSH was sharply decreased, and H2O2 content was dramatically
      increased. CONCLUSION: These results indicated that combination of ascorbic acid
      and sodium selenite may induce the redifferentiation of human gastric cancer
      cells and inhibit cell growth by virtue of enhancing the activities of
      antioxidative enzymes and inducing the formation of H2O2, and altering the cell
      redox status. Combination of ascorbic acid and sodium selenite may be a potent
      anticancer agent for human gastric cancer.

PMID- 12500664
TI  - Abnormal reactions of free radicals and oxidative damages in the bodies of
      patients with chronic glomerulonephritis.
AB  - OBJECTIVE: To study the abnormal reactions of a series of free radicals and the
      oxidative damages induced by free radical abnormal reactions in the bodies of
      patients with chronic glomerulonephritis. METHODS: Eighty chronic
      glomerulonephritis patients (CGNP) and eighty healthy adult volunteers (HAV) were
      enrolled in a random control study, in which concentrations of nitric oxide (NO)
      in plasma, lipoperoxides (LPO) in plasma and in erythrocytes, and vitamin C (VC),
      vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as activities of
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in
      erythrocytes were determined with spectrophotometric assays. RESULTS: Compared
      with the average values of the above biochemical parameters in the HAV group, the
      average values of NO in plasma, and LPO in plasma and erythrocytes in the CGNP
      group were significantly increased (P = 0.0001), while those of VC, VE and beta
      CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the CGNP
      group were significantly decreased (P = 0.0001). Pearson product-moment
      correlation analysis showed that with increase of the concentration of blood
      creatinine as well as prolongation of the course of disease in the CGNP, the
      concentrations of NO in plasma, and LPO in plasma and erythrocytes in the CGNP
      increased gradually, while the concentrations of VC, VE and beta-CAR in plasma as
      well as the activities of SOD, CAT and GPX in erythrocytes in the CGNP decreased
      gradually (P = 0.002454-0.000001). The relative risk ratio (RR) of the above
      biochemical parameters reflecting oxidative damages in the bodies of CGNP ranged
      from 6.061 to 72.429. The reliability coefficient (alpha) that the above
      biochemical parameters were used to reflect the oxidative damages of the CGNP was
      0.8137, standardized item alpha = 0.9728, Hotelling's T-Squared = 1135680.191, F
      = 53274.6478, P = 0.000001. CONCLUSIONS: The findings in this study show that in
      the bodies of CGNP a series of free radical chain reactions result in severe
      pathological aggravation and induce oxidative damages in their bodies. Therefore,
      suitable dose of antioxidants should be supplemented to them so as to alleviate
      oxidative damages in their bodies.

PMID- 12500665
TI  - Effect of body mass index on all-cause mortality and incidence of cardiovascular
      diseases--report for meta-analysis of prospective studies open optimal cut-off
      points of body mass index in Chinese adults.
AB  - OBJECTIVE: To verify the optimal cut-off points for overweight and obesity in
      Chinese adults based on the relationship of baseline body mass index (BMI) to all
      cause mortality, and incidence of cardiovascular diseases from pooled data of
      Chinese cohorts. METHODS: The prospective study data of existing cohort studies
      in China were collected, and the age-adjusted all-cause mortality stratified by
      BMI were estimated. The similar analysis was repeated after excluding deaths
      within the first three years of follow-up and after excluding smokers. The
      incidence of age-adjusted coronary heart disease (CHD) and stroke stratified by
      BMI were also analyzed. Multiple Cox regression coefficients of BMI for the
      incidence of CHD and stroke after controlling other risk factors were pooled
      utilizing the methods of weighting by inverse of variance to reveal whether BMI
      had independent effect and its strength on the incidence of CHD and stroke.
      RESULTS: The data of 4 cohorts including 76,227 persons, with 745,346 person
      years of follow-up were collected and analyzed. The age-adjusted all-cause
      mortality stratified by BMI showed a U-shaped curve, even after excluding deaths
      within the first three years of follow-up and excluding smokers. Age-adjusted all
      cause mortality increased when BMI was lower than 18.5 and higher than 28. The
      incidence of CHD and stroke, especially ishemic stroke increased with increasing
      BMI, this was consistent with parallel increasing of risk factors. Cox regression
      analysis showed that BMI was an independent risk factor for both CHD and stroke.
      Each amount of 2 kg/m2 increase in baseline BMI might cause 15.4%, 6.1% and 18.8%
      increase in relative risk of CHD, total stroke and ischemic stroke. Reduction of
      BMI to under 24 might prevent the incidence of CHD by 11% and that of stroke by
      15% for men, and 22% of both diseases for women. CONCLUSION: BMI < or = 18.5, 24
      27.9 and > or = 28 (kg/m2) is the appropriate cut-off points for underweight,
      overweight and obesity in Chinese adults.

PMID- 12500666
TI  - Polymorphism of glutathione S-transferase T1, M1 and P1 genes in a Shanghai
      population: patients with occupational or non-occupational bladder cancer.
AB  - OBJECTIVE: Glutathione S-transferases are involved in the conjugation of
      xenobiotics. To explore whether GSTs polymorphisms are involved in the
      development of occupational or non-occupational bladder cancer, polymorphism
      frequencies of GSTT1, M1 and P1 were investigated in a normal population, which
      had been settled in a rural area in Shanghai suburb for at least 5 generations as
      well as in a group of patients with benzidine exposure related occupational
      bladder cancer in Shanghai dyestuff industry and a group of patients with non
      occupational bladder cancer. METHODS: PCR based procedures were performed in the
      study populations to confirm the genotypes of GSTT1, M1 and P1. RESULTS: The
      polymorphisms at locus of GSTP1-A1578G in the normal population differed
      significantly from those in Caucasians or African Americans. All the subjects
      genotyped so far (n = 118) bore only homogenous wild genotype (C2293/C2293) at
      GSTP1-C2293T locus. This locus seemed to be a monomorphic in Shanghai population.
      No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could
      be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or
      GG genotype corresponding a less stable and less effective isozyme protein was
      detected in patients with benzidine related occupational bladder cancer, compared
      with that in the normal population though a statistical significance was not yet
      reached (P = 0.09, OR = 1.96, 95% CI 0.89-4.32). CONCLUSION: This study suggests
      that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not
      have a clear impact on bladder cancer incidence in a Shanghai population. It
      seems that GSTP1 polymorphism is not associated with non-occupational bladder
      cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with
      benzidine related occupational bladder cancer, and further work is needed to
      confirm if GSTP1 AG or GG genotype plays a role in the development of
      occupational bladder cancer.

PMID- 12500667
TI  - Gamma-irradiation effect: variation of photosynthetic activity of Euglena.
AB  - OBJECTIVE: To study the effects of gamma-ray irradiation on carbon fixation
      (Specific production rate: SPR), CO2 utilization efficiency (CUE) and electron
      transfer rate (ETR) in the photosynthetic flagellate Euglena gracilis strain Z in
      a dose-response dependent manner. METHODS: Euglena cells were cultured in an
      inorganic nutrient medium containing ammonium chloride or proteose peptone. Cells
      were exposed to gamma-ray at 5 doses (0, 100, 250, 350, 500 Gy for water). Five
      days after irradiation, three photosynthetic activities were measured. SPR, which
      is a carbon uptake rate per unit carbon mass, was determined by 13C tracer
      methodology. CUE was evaluated using a relation of carbon isotope fractionation
      in Calvin cycle. ETR in photosystem II (PS II) was measured by a chlorophyll
      fluorescence analysis. RESULTS: Even at a dose of 500 Gy, 80% of ETR of the non
      irradiated control (0 Gy) was sustained, while SPR and CUE were about half the
      level in the non-irradiated control at 500 Gy. Furthermore, the dose response of
      ETR was considerably different from the others. CONCLUSION: Our findings suggest
      that not only PS II but also the Calvin cycle in the photosynthetic system is
      affected by gamma ray irradiation.

PMID- 12500668
TI  - Study on chromosome damage among nurses occupationally exposed to antineoplastic
      drugs in an oncology department.

PMID- 12500669
TI  - [The BCL-xL and ACR-1 genes promote differentiation and reduce apoptosis in
      muscle fibers of mdx mice].
AB  - The effects of the human BCL-xL and ACR-1 genes on dystrophin expression in cross
      striated muscle fibers (CSMF) and on CSMF viability were studied in mdx mice
      after ballistic cotransfection with the human dystrophin minigene. In control
      mice, the proportion of dystrophin-positive (D(+)) and dying CSMF were 2.1 +/-
      0.1 and 2.1 +/- 0.3%, respectively. Introduction of the dystrophin minigene (20
      micrograms of the pSG5dys plasmid) increased the proportions of D(+) and dying
      CSMF to 5.6 +/- 1.4% and 4.5 +/- 0.9%, respectively. When pSG5dys was introduced
      along with the pSFFV-Neo plasmid carrying the BCL-xL gene (10 micrograms of each
      plasmid per shot), the death of CSMF decreased to 3.7 +/- 1% and the proportion
      of D(+) CSMF significantly (P < 0.05) increased to 12.2 +/- 2.2%. Contransfection
      with the dystrophin minigene and the BCL-xL gene at 20 micrograms of each plasmid
      per shot did not stimulate generation of D(+) CSMF, but did reduce the CSMF death
      to 1.5 +/- 0.3%. Introduction of pSG5dys along with the pRc-CMV-10.1 plasmid
      containing the ACR-1 gene (10 micrograms of each plasmid per shot) reduced the
      proportion of D(+) CSMF to 1.1 +/- 0.5% and significantly reduced the proportion
      of dying CSMF to 0.9 +/- 0.3% as compared with the proportions observed in intact
      mice or in mice subjected to transfection with pSG5dys. Introduction of the
      pSG5dys plasmid substantially reduced the proportion of CSMF with peripheral
      nuclei, suggesting disturbed CSMF differentiation. After cotransfection with the
      human-dystrophin minigene, the BCL-xL and ACR-1 genes did not affect the extent
      of CSMF differentiation as compared with that observed in the case of the
      dystrophin minigene alone. Thus, ballistic transfection of mdx mice with the
      human dystrophin gene used along with the BCL-xL or ACR-1 gene was shown to
      suppress the death of muscle fibers and to expedite dystrophin synthesis and cell
      differentiation.

PMID- 12500670
TI  - [Formation of ARS-independent miniplasmids upon transformation of yeast Pichia
      methanolica with DNA molecules containing "transforming" and "nontransforming"
      genes].
AB  - In the study of transforming DNA molecules in cells of the methylotrophic yeast
      Pichia methanolica, it was found that the efficiency of transformation and the
      possibility of autonomous replication of hybrid plasmids and miniplasmids
      consisting of only transforming gene (Trg) sequences do not depend on the
      presence of ARS sequences with the canonical structure, such as 2 microns DNA in
      the yeast Saccharomyces cerevisiae. Data supported a suggestion about the
      existence of the relationship between gene transforming activity, its replicative
      ability, and transcription. The efficiency of vector activity of Trg is not
      sufficient to provide the transformation of other sequences of transforming DNA
      (tDNA). The loss of nonselected sequences of tDNA observed upon transformation is
      the result of rearrangements and deletions and is associated with the activity of
      cellular systems involved in nucleic acid metabolism. Miniplasmids similar in
      structure were shown to differ in their stability in independent transformants.
      The rate of loss of autonomously replicating plasmids strongly varied (from 1 to
      99%) under nonselective conditions and nearly did not depend on plasmid
      structure.

PMID- 12500671
TI  - [Allelic polymorphism of the tem(M) determinant in Mycoplasma hominis and
      Ureaplasma urealyticum clinical isolates resistant to tetracyclines].
AB  - Of the 130 clinical isolates of Mycoplasma hominis from patients with nonspecific
      inflammatory diseases of the urogenital tract (UGT), approximately 10% contained
      the tet(M) gene after the course of treatment with tetracyclines. This gene was
      found in nine (25%) of the 36 Ureaplasma urealyticum clinical isolates. The
      nucleotide sequence of 13 tet(M) genes in TcR clinical isolates of M. hominis and
      five genes in U. urealyticum TcR clinical isolates was determined. A comparison
      of nucleotide sequences of eight tetM genes of different origin and tet(M) genes
      of Gardnerella vaginalis and M. hominis and U. urealyticum clinical isolates
      showed that the mosaic structure of the tet(M) gene is completely identical in 11
      of 13 M. hominis TcR isolates but belongs to an unidentified allele different
      from those described earlier, Another new allelic variant of tet(M) was found in
      two isolates. In three of five TcR clinical isolates of U. urealyticum, a tet(M)
      gene, whose mosaic structure was identical to that of tet(M) reported previously
      for ureaplasmas, and also two new allelic variants, which have not been described
      so far, were found.

PMID- 12500672
TI  - [Phenogenetic characterization of a group of giant Phi KZ-like bacteriophages of
      Pseudomonas aeruginosa].
AB  - A comparative study was made of a group of Pseudomonas aeruginosa virulent giant
      DNA bacteriophages similar to phage phi KZ in several genetic and phenotypic
      properties (particle size, particle morphology, genome size, appearance of
      negative colonies, high productivity, broad spectrum of lytic activity, ability
      to overcome the suppressing effect of plasmids, absence of several DNA
      restriction sites, capability of general transduction, pseudolysogeny). We have
      recently sequenced the phage phi KZ genome (288,334 bp) [J. Mol. Biol., 2002,
      vol. 317, pp. 1-19]. By DNA homology, the phages were assigned to three species
      (represented by phage phi KZ, Lin68, and EL, respectively) and two new genera
      (phi KZ and EL). Restriction enzyme analysis revealed the mosaic genome structure
      in four phages of the phi KZ species (phi KZ, Lin21, NN, and PTB80) and two
      phages of the EL species (EL and RU). Comparisons with respect to phage particle
      size, number of structural proteins, and the N-terminal sequences of the major
      capsid protein confirmed the phylogenetic relatedness of the phages belonging to
      the phi KZ genus. The origin and evolution of the phi KZ-like phages are
      discussed. Analysis of protein sequences encoded by the phage phi KZ genome made
      it possible to assume wide migration of the phi KZ-like phages (wandering phages)
      among various prokaryotes and possibly eukaryotes. Since the phage phi KZ genome
      codes for potentially toxic proteins, caution must be exercised in the employment
      of large bacteriophages in phage therapy.

PMID- 12500673
TI  - [Sex chromosome homologies between human and fish revealed by the chromosome
      painting method].
AB  - Human sex chromosome-specific probes were hybridized to metaphase spreads of
      three fish species, Monopterus albus Zuiew, Danio rerio and Mastacembelus
      aculeatus Basilewsky, to reveal evolutionary conservation of sex chromosomal
      segments between distantly related species of vertebrates. The human X
      chromosomal paint disclosed 4, 8, and 6 conserved syntenic segments in the
      karyotypes of the three fish species respectively, which were scattered in
      several pairs of homologous chromosomes. But no conserved segment was identified
      in our experiments when the human Y chromosomal probes were used. The evolution
      of the X chromosome of vertebrates is discussed.

PMID- 12500674
TI  - [Genetic structure of populations of the Colorado potato beetle Leptinotarsa
      decemlineata (Coleoptera: Chrysomelidae)].
AB  - The genetic structure of a Colorado potato beetle population from Kiev oblast was
      examined by cluster analysis of individual RAPD patterns. The obtained clustering
      indicates that the population is structured. This may be explained by adaptation
      to pyrethroid insecticides used for controlling the population size of this pest.
      Micro-evolutionary factors affecting the genetic structure of local populations
      of Colorado potato beetle are discussed.

PMID- 12500675
TI  - [Variability of life cycle traits in Iris pumila juvenile plants: plant shoots
      and roots dynamics].
AB  - In this study I analyzed dynamic of ramet number on 18 half-sib and 63 full-sib
      families of rhizomatous perennial herb Iris pumila originating from two Deliblato
      Sand populations and grown in two nutrient levels (full strength and 1/10 of full
      strength Hoagland solution). Contrary to most studies dealing with response to
      different nutrient availability, I failed to detect significant mean nutrient
      level effect on dynamic of module emergence. Such absence of consistent response
      to tenfold variation in solution strength indicate that I. pumila have low
      saturation rates of nutrient uptake and presumably experienced both utilized
      nutrition levels as rich ones. Genetic variability for plastic response was
      lacking either. On the other hand, presence of between-population differentiation
      for the trait itself indicates that I. pumila harbors considerable amounts of
      within-species genetic variability for ramet dynamics.

PMID- 12500676
TI  - [Hordein polymorphism in barley varieties fom North Africa].
AB  - Using starch gel electrophoresis, we examined polymorphism of hordein encoded by
      loci Hrd A, Hrd B, and Hrd F in 77 accessions of local barley varieties from
      North African countries (9 from Marocco, 22 from Algeria, 7 from Tunisia, and 39
      from Egypt). For loci Hrd A, Hrd B, and Hrd F, respectively 35, 43, and 5 alleles
      were found. The existence of families of blocks of hordein components encoded by
      Hrd A and Hrd B was demonstrated. The estimation of genetic distances and cluster
      analysis showed similarity of barley populations from different North African
      countries with regard to alleles of the hordein-coding loci. We suggest that
      polymorphism at the hordein-coding loci in the populations examined has been
      mainly formed beyond North Africa, where barley has been repeatedly introduced.
      Apparently, the examined populations from Ethiopia and Egypt are not directly
      associated.

PMID- 12500677
TI  - [Effects of the mutant gene wellhaarig in chimeric mice].
AB  - The mutant gene wellhaaring (we) confers the waved coat in mice, which is most
      pronounced in homozygotes at 10 to 21 days of postnatal development. Abnormal
      hair growth and structure in the we/we mutant mice results from defective cell
      differentiation in the inner root sheath of a hair follicle. To localize the site
      of the we gene action, we obtained ten chimeric mice by aggregation of the early
      C57BL/6-2we/we and BALB/c embryos. The chimera coat was waved, shaggy, or almost
      normal depending on the percentage of the mutant component. In the we/we +/+
      chimeric animals of the first generation (G1) aged 21 days, both mutant and
      normal hair phenotypes were observed, which was especially discernible in zigzag
      hair. Note that none of the chimeras exhibited the alternating patterns of
      transversely oriented stripes or patches of either mutant or normal hair; i.e.,
      they had a mixed parental hair phenotype. We also did not observe the animals
      with an intermediate phenotype, which suggests a discontinuous hair formation in
      chimeras according to the "all or nothing" principle. The data obtained indicate
      that the dermal papilla cells of a hair follicle are the sites for the we gene
      action. During the embryonic development, dermal cells are strongly mixed, which
      accounts for the lack of the clear-cut transverse stripes of either mutant or
      normal hair. The mutant gene we is probably responsible for a disrupted induction
      signal from the dermal papilla towards ectodermal cells of a hair follicle.

PMID- 12500678
TI  - [Genetic divergence of Far Eastern dace species belonging to the genus Tribolodon
      (Pisces, Cyprinidae) and closely related taxa].
AB  - Based on a biochemical-genetic approach, heterozygosity and divergence of
      structural genes of 30 enzyme loci were analyzed in six dace species. In
      addition, intra- and interspecific divergence of gene expression was analyzed
      based on a sample of 12 to 15 loci. Mean heterozygosities per individual varied
      as follows: Tribolodon species, Hobs = 0.007 +/- 0.007 and Hexp = 0.007 +/-
      0.007; T. ezoe, Hobs = 0.045 +/- 0.016 and Hexp = 0.067 +/- 0.029. Several
      variants of genetic distances were estimated. Standard Nei's distances (DN)
      varied from 0.145 to 0.284 in four dace species studied. As related to Tribolodon
      dace species, the following genetic distances were obtained for two members of
      other genera: Pseudaspius leptocephalus, DN = 0.269; Leuciscus waleckii, DN =
      0.769. Based on the distance matrices, different clustering algorithms were
      realized. The main feature shared by different dendrograms was a separate
      position of the cluster joining Far-Eastern dace species, to which P.
      leptocephalus and L. waleckii are successively added. Among the species studied,
      the proportion of loci similar by expression (E) varied from 87 to 100%. The
      greatest difference was found between anadromous and nonanadromous ecotypes of T.
      hakonensis, E = 67%. The following conclusions can be made: (1) Four studied
      species of the genus Tribolodon are rather well genetically differentiated.
      Diagnostic loci are available. (2) A nominal dace species, T. species, should be
      considered the fourth isolated species of this genus, which is confirmed by its
      recent zoological acceptance of this species. (3) The origin and divergence of
      dace species belonging to the genus Tribolodon are relatively late (1 to 3 Myr
      ago) historical events. (4) Taxonomically, the genus Tribolodon belong to the
      tribe Pseudaspinini together with P. leptocephalus, which is confirmed by genetic
      data. (5) Data on heterozygosity and the divergence of structural and regulatory
      elements of genome, along with the proposed scheme of speciation types, suggest
      the following speciation modes for the species studied: for four species,
      adaptive divergence and for two species, genetic transformation.

PMID- 12500679
TI  - [Mitochondrial DNA variation in Russian populations of Stavropol krai, Orel and
      Saratov oblasts].
AB  - Mitochondrial DNA (mtDNA) polymorphism was examined in three Russian populations
      from the European part of Russia (Stavropol krai, Orel oblast, and Saratov
      oblast). This analysis showed that mitochondrial gene pool of Russians was
      represented by the mtDNA types belonging to haplogroups H, V, HV*, J, T, U, K, I,
      W, and X. A mongoloid admixture (1.5%) was revealed in the form of mtDNA types of
      macrohaplogroup M. Comparative analysis of the mtDNA haplogroup frequency
      distribution patterns in six Russian populations from the European part of Russia
      indicated the absence of substantial genetic differences between them. However,
      in Russian populations from the southern and central regions the frequency of
      haplogroup V (average frequency 8%) was higher than in the populations from more
      northern regions. Based on the data on mtDNA HVS1 sequence variation, it was
      shown that the diversity of haplogroup V in Russians (h = 0.72) corresponded to
      the highest h values observed in Europe. The reasons for genetic differentiation
      of the Russian population (historical, ecological, and adaptive) are discussed.

PMID- 12500680
TI  - [Mapping genes of complex diseases in genetic isolates of Dagestan].
AB  - Original results of the analysis of genetic linkage between some genomic markers
      and two complex clinical phenotypes, schizophrenia and mental retardation, in
      pedigrees from Dagestan genetic isolates are described. Interpopulation
      differences in the epidemiology of the complex phenotypes were studied and in
      their genetic linkage was demonstrated. These differences are evidently related
      to the genetic structure of the isolates determined by their genetic history. The
      MR epidemiological index characterizing the lifetime morbid risk of schizophrenia
      varies in the Dagestan isolates studied from 0 to 4.95%, which is almost five
      times higher than the average worldwide population rate, 1%. Comparative genetic
      mapping permitted determination of the most probable genetic linkages and
      associations of loci from chromosomal regions 17p11.1-12, 3q13.3, and a locus
      from 22q with schizophrenia and locus 12q23 with mental retardation. There is
      evidence that this approach is effective for detailed study of the relationship
      between the genetic (allele and locus) and clinical heterogeneity of complex
      diseases, which favors successful identification of the genes determining them.
      The study of linkage disequilibrium (LD) in genetic isolates of Daghestan
      populations (which have a common genetic background) may be an effective
      methodological approach for revealing the numerous contradictory results of
      mapping of the same genes of complex disease performed by different researchers
      in different regions of the world.

PMID- 12500681
TI  - [Analysis of the allele polymorphism of (CTG)n and (GAG)n triplet repeats in DM,
      DRPLA, and SCA1 genes in various populations of Russia].
AB  - Polymorphism of highly polymorphic triplet repeats CTG of the 3'-untranslated
      region of the myotonin protein kinase gene and CAG of the genes associated with
      dentatorobral-pallidoluysian atrophy (DRPLA, or Hew River syndrome) and
      spinocerebellar ataxia type 1 (SCA1) was analyzed in several ethnic populations
      of Russia. A difference in allele spectra of the three genes was demonstrated for
      populations differing in ethnic origin.

PMID- 12500682
TI  - [Mitochondrial DNA variation in Kets and Nganasans and the early peoples of
      Northern Eurasia].
AB  - Mitochondrial DNA (mtDNA) variation was studied in 38 Kets and 24 Nganasans, the
      indigenous inhabitants of the north of the Yenisey River Basin and the Taimyr
      Peninsula. The results were compared with the analogous data obtained for 59
      Kondinski and 39 Sos'vinski Mansi. As a whole, mitochondrial gene pool of Mansi,
      Nganasans, and Kets was characterized by unique combination of European-specific
      (H, H2, H3, H8, U2, U4, U5, U7, J2, and W) and Asian-specific (A, C, D, and Z)
      mtDNA haplogroups. Specific features of the haplogroup geographical distribution
      along with the results of phylogenetic reconstruction favor the hypothesis of the
      genetic trace left in Eastern Cis-Urals and the adjacent Siberian territories by
      early migrations from the Near East.

PMID- 12500683
TI  - [Materials for studying the gene pools of Russia and neighboring countries: the
      Russian population of the Pskov region].
AB  - The distributions of the genes and haplotypes for blood groups ABO, MN, Rhesus,
      P1, Lewis, and Kell-Cell-ano and biochemical markers of the genes of loci HP, GC,
      C'3, Tf, 6PGD, GLO1, ESD, ACP1, and PGM1 (including subtypes) were studied in 116
      Russian subjects born in the Pskov oblast. Differences of this group from other
      Russian populations with respect to genetic structure were found.

PMID- 12500684
TI  - [Polymorphism of glutathione S-transferase genes M1 and T1 in patients with motor
      neuron disease from the city of Moscow].
AB  - Comparison of the frequency distributions of alleles, genotypes, and genotype
      combinations of genes GSTM1 and GSTT1 did not show statistically significant
      differences between patients with motor neuron disease (MND) and a random sample
      from the Moscow population. Apparently, these genes are not involved in MND
      pathogenesis in these patients.

PMID- 12500685
TI  - [Mercury-resistant bacteria from permafrost sediments and prospects for their use
      in comparative studies of mercury resistance determinants].
AB  - Mercury-resistant bacteria were isolated from permafrost sediments of Kolyma
      lowland and Canada existing over five thousand to two million years. Their
      content was shown to vary within the range 0.001-2.9% and to depend on the amount
      of mercury in sampling sites (coefficient of correlation 0.75). A collection of
      mercury-resistant bacterial strains was created. In this collection, various
      representatives of both Gram-positive bacteria (Bacillus, Exiguobacterium,
      Micrococcus, Arthrobacter) and Gram-negative bacteria (Pseudomonas,
      Acinetobacter, Plesiomonas, Myxobacteriales) were identified. Most resistant
      bacteria were found to contain determinants homologous to mer-operons of
      contemporary bacteria. The isolated strains of paleobacteria are proposed to be
      used for a comparative structural study of contemporary and ancient plasmids and
      transposons carrying mercury resistance determinants.

PMID- 12500687
TI  - [The use of artificial neural networks for Aegilops species identification based
      on analysis of D genomes].
AB  - The possibilities of the use of artificial neural networks (ANNs) for
      identification of some polyploid species of genus Aegilops based on the idiograms
      of their D genomes were demonstrated.

PMID- 12500686
TI  - [NOR (nucleolar organizer region) activity in wheat species with different ploidy
      levels treated with phytohormones].
AB  - The effects of the phytohormones 6-benzylaminopurine (BAP) and 24-epibrassinolide
      (EB) on the nucleolar sizes in the interphase nuclei of root meristem were
      studied using the silver-staining procedure in wheat species with different
      ploidy levels (a polyploid series). In addition, the effects of the phytohormones
      on the cell mitotic activity in the roots of 5-day-old seedlings were studied.
      The higher the wheat species ploidy level, the higher its sensitivities to BAP
      and EB were. In diploid wheat, the maximum increase in the nucleolar organizing
      region (NOR) activity was observed after treatment with considerably higher
      phytohormone concentrations compared to tetra- and hexaploid wheat species. The
      phytohormone treatment increased both the sizes and the number of nucleoli in
      meristematic cells of seedling roots in all wheat species studied. It was assumed
      that the differences between the responses of wheat species with three different
      ploidy levels to different concentrations of phytohormones were related to their
      effects on the methylation/demethylation of cytosine residues in the rDNA
      promoter region.

PMID- 12500688
TI  - How sick was J.F.K.?

PMID- 12500690
TI  - The mother of all dogs.

PMID- 12500689
TI  - Flunking lunch.

PMID- 12500691
TI  - How to kill a cancer.

PMID- 12500692
TI  - Black tide.

PMID- 12500693
TI  - Stuffing yourself healthy.

PMID- 12500694
TI  - A hurry-up lifestyle can hurt the young.

PMID- 12500695
TI  - Overexpression of bradykinin type 2 receptors on glioma cells enhances bradykinin
      mediated blood-brain tumor barrier permeability increase.
AB  - Variations in the expression levels of bradykinin (BK) type 2 receptors (B2R) in
      different brain tumors may explain variable increases in BK-mediated blood-brain
      tumor barrier (BTB) permeability. This study investigated whether elevation of
      the B2R expression levels on glioma cells enhances BK-mediated BTB permeability
      increases. Stable transfectants of C6 rat glioma cells overexpressing B2R were
      established by transfection with recombinant vectors harboring rat B2R cDNA
      sequence. Elevated B2R expression levels in transfectants were confirmed by
      quantitative real-time PCR, Western blots, and [3H]-BK binding studies. BTB
      permeability was quantified with autoradiography and expressed as a
      unidirectional transport constant, Ki, for [14C]-alpha-aminoisobutyric acid (AIB:
      Mr 103), using a rat brain tumor model. Baseline Ki values in tumors
      overexpressing B2R were not significantly higher than in control tumors. Ki
      values after BK treatment in tumors overexpressing B2R, however, were
      significantly higher than in control tumors. Western blots confirmed that B2R
      expression levels in vivo in tumors overexpressing B2R remained higher than in
      control tumors. These results suggested that alteration of B2R expression levels
      on tumor cells could modulate BK-mediated BTB permeability. Therefore, B2R
      expression levels in human glioma could be used to analyze the treatment results
      of patients undergoing treatment involving BK-modulated BTB permeability.

PMID- 12500696
TI  - Prognostic value of concordant seizure focus localizing data in the selection of
      temporal lobectomy candidates.
AB  - This study was performed to test the hypotheses that (a) resection of the
      temporal lobe epileptic focus, amenable to noninvasive as opposed to invasive
      localization, is associated with superior seizure outcome and (b) that quadruple
      (versus lesser degrees of) concordance of seizure focus localizing data predicts
      superior seizure-free outcome. Eighty-three patients underwent invasive (subdural
      EEG) and/or noninvasive (video/scalp-EEG, SPECT, PET, MRI, neuropsychological
      testing) evaluation. All patients underwent anterior temporal lobectomy and
      amygdalohippocampectomy (ATL/AH) and seizure outcome was assessed at minimum one
      year follow-up. At 34.8 +/- 2.5 months following ATL/AH, outcome was superior for
      patients in whom the seizure focus was amenable to noninvasive compared to
      invasive localization (80% versus 40% seizure-free, X2 = 14.03, p < 0.05).
      Seizure outcome was superior for patients with quadruple, compared to all lesser
      degrees of, concordance of seizure focus localizing data (85% versus 51% seizure
      free, X2 = 7.34, p < 0.05). Post-ATL/AH, seizure outcome is superior in patients
      (1) harboring an epileptic focus amenable to noninvasive localization and (2)
      with quadruple concordance of seizure focus localizing data. These findings
      support the development of temporal lobectomy selection criteria including up to
      four invasive and/or noninvasive concordant seizure focus localizing techniques.

PMID- 12500697
TI  - Prognostic value of SSEP in early aneurysm surgery after SAH in poor-grade
      patients.
AB  - We evaluate the prognostic value of somatosensory evoked potentials (SSEP) in
      poor-grade patients after early surgery for aneurysmal subarachnoid hemorrhage
      compared to the Hunt and Hess (H&H) and WFNS scales. Ninety patients with
      angiographically proven aneurysms graded H&H IV or V were evaluated
      retrospectively. The aneurysms of 72 patients were clipped. In 53 out of 72
      patients 147 SSEP examinations were recorded. The SSEP were classified according
      to the central conduction time (CCT) and the number of cortical potentials.
      Outcome was determined according to the Glasgow Outcome Scale. To evaluate the
      predictability of the SSEP to clinical grading scales receiver operating
      characteristic (ROC) analysis was done. The H&H scale did not demonstrate
      statistically significant predictability for poor-grade patients. The WFNS scale
      predicted the outcome for only one group (survival/death) (p = 0.035).
      Predictability of outcome by the SSEP was statistically confirmed. Normal CCT
      indicated a potential for a good recovery, but not consistently so. Bilaterally
      enhanced CCT was predictive of a poor outcome. Bilateral lack of cortical
      responses was always related to fatal outcome. ROC analysis confirmed that SSEP
      are superior to clinical grading scales in determining prognosis in poor-grade
      patients. In doubt, whether early aneurysm surgery or conservative treatment in a
      poor-grade patient should be done, SSEP will be helpful.

PMID- 12500698
TI  - Blood flow and ionic responses in the awake brain due to carbon monoxide.
AB  - This study examined the effect of 2000 ppm CO on the brain of an awake rat.
      Measurements of regional perfusion as well as metabolic, ionic and electrical
      activities were used to examine whether mechanisms responsible for changes in
      brain perfusion were separable from those attributable to compromises in neuronal
      metabolism. Exposure to 2000 ppm CO resulted in elevation of cerebral blood flow.
      The stability of mitochondrial NADH redox level during CO exposure indicated that
      tissue hypoxia did not develop. The elevation in blood flow was inhibited by L
      nitroarginine methyl ester, indicating that nitric oxide was responsible for the
      CO-induced elevation in blood flow. Exposure to 2000 ppm CO also triggered a
      significant decrease in pH and rise in extracellular potassium ion, possibly due
      to ion-pump inhibition. The amplitude of the electrocorticogram wave activity
      decreased, indicative of a compromise to physiological activity. These changes
      were not observed in rats anesthetized with pentobarbital during CO exposure,
      although anesthesia had no effect on the CO-induced elevation in blood flow and
      there was still no change in mitochondrial NADH redox level. We concluded that CO
      acts by separate mechanisms to alter cerebral vasoactivity and neuronal metabolic
      responses and that both processes are independent of hypoxic stress.

PMID- 12500699
TI  - Axial lateropulsion as a sole manifestation of lateral medullary infarction: a
      clinical variant related to rostral-dorsolateral lesion.
AB  - A 63-year-old woman presented with an isolated axial lateropulsion as a sole
      manifestation of lateral medullary infarction. She had no vertigo, nystagmus,
      dysphagia, hiccup, facial/hemisensory loss, Horner syndrome, and limb ataxia.
      Brain MRI showed a small infarct selectively involving the most dorsolateral
      portion of the rostral medulla. This patient illustrates that lateral medullary
      infarction may present as an isolated lateropulsion. The possible mechanism of an
      isolated lateropulsion is described.

PMID- 12500700
TI  - Nimodipine ameliorates trauma-induced cochlear neuronal death.
AB  - Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)
      activated enzymes and subsequent spiral ganglion cell death. Therefore,
      preventing intracellular calcium overload by using Ca2+ channel antagonists may
      become an important countermeasure to spiral ganglion cell death. We
      experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine)
      can rescue traumatized cochlear neurons from degeneration. A group of rats (n =
      6) was pre-operatively treated with nimodipine for one week and compression
      injury was applied to the cerebellopontine angle portion of the cochlear nerve in
      a highly quantitative fashion. The rats from the compression with nimodipine
      treatment groups were post-operatively treated with nimodipine for 10 days and
      killed for histological examination. The histological analysis of the temporal
      bones revealed that the spiral ganglion cells in the basal turn of the cochlea
      where the magnitude of traumatic impact had been the least in our experimental
      condition were rescued in a statistically significant fashion in the compression
      with nimodipine treatment group. The results of the present study indicate that
      nimodipine may become an intra- and post-operative important adjunct to raise the
      rate of hearing preservation in vestibular schwannoma excision or other
      cerebellopontine angle surgical interventions.

PMID- 12500701
TI  - Mild focal cerebral ischemia in the rat. The effect of local temperature on
      infarct size.
AB  - We aimed at investigating a new model of mild focal cerebral ischemia in rats
      with repeated, noninvasive magnetic resonance scanning combined with histology.
      Magnetic resonance imaging yielded information about infarct development enabling
      us to test the putative growth of the infarct over time. The effect of local
      temperature at the occlusion site in this model was furthermore tested. Thirty
      three Wistar rats were subjected to 30 min of simultaneous common carotid artery
      and distal middle cerebral artery occlusion or sham treatment. Animals were
      magnetic resonance-scanned repeatedly between day one and day 14 after surgery,
      then sacrificed, and paraffin brain sections stained. All animals scanned 24 h
      after reperfusion showed an area of edema in the affected cortex, which later was
      identified as an infarct. Animals with a temperature of 33.9 +/- 1.5 degrees C at
      the MCA site (hypothermic) showed smaller infarcts (14.4 +/- 10 mm3) than animals
      with normothermic local temperature (36.7 +/- 0.2 degrees C, 57.7 +/- 26.4 mm3).
      Infarct size was maximal on day 3 after ischemia but decreased as edema subsided.
      Infarct volumes from histology and magnetic resonance imaging correlated well.
      The model reproducibly yielded cortical infarcts, which did not grow after edema
      had subsided. Local temperature had a considerable effect on final infarct size.

PMID- 12500702
TI  - Assessment of prognostic factors in severe traumatic brain injury patients
      treated by mild therapeutic cerebral hypothermia therapy.
AB  - This study analyzed the predictable factors of outcome such as neuro-parameters
      and systemic complications to elucidate the indications for therapeutic
      hypothermia. In our institute, 35 patients with severe head injury (Glasgow Coma
      Scale 3-7) were treated with mild hypothermia therapy (33 degrees-35 degrees C).
      Twenty-two of these 35 patients underwent complete neuromonitoring and outcome
      assessments by Glasgow Outcome Scale (GOS) at three months after injury. GOS of
      hypothermia group was significantly better than another patient group which was
      treated without mild hypothermia therapy. The hypothermia group was divided into
      two groups: good outcome (GOOD) (good recovery or moderate disability; n = 9,
      40.9%) and poor outcome (POOR) (severe disability, vegetative state, or death; n
      = 13, 59.1%). The mean age (mean 30.2 years, range 9-46) was significantly lower
      in GOOD than in POOR (mean 45.2 years, range 17-62). Patients aged over 50 years
      had poor outcome. CPP was significantly higher in GOOD during hypothermia. All
      patients with thrombocytopenia had poor outcome. Hypothermia therapy can improve
      outcome in patients with traumatic brain injury who are younger than 50 years
      old, without severe brain damage, and if improvement of cerebral perfusion is
      expected. Systemic complications must be prevented as far as possible by
      combination with other therapies.

PMID- 12500703
TI  - Caspase inhibitors reduce the apoptotic but not necrotic component of kainate
      injury in primary murine cortical neuronal cultures.
AB  - Excitotoxicity has been demonstrated to play a major role in ischemic neuronal
      injury. While the necrotic component of excitotoxicity has been well
      demonstrated, apoptosis has also been shown to play a role. We sought to
      quantitate and modulate the apoptotic component of kainate-induced injury.
      Experiments were performed in mouse primary cortical neuronal cultures after
      three or 10 days in vitro. Cell death was assessed by Hoechst/propidium iodide
      staining and cell counting. Apoptosis was further confirmed with inhibition by
      caspase inhibitors. Exposure of three-day old neurons to 100 microM kainate
      produced an injury in which 56% +/- 0.9% of cells showed apoptotic nuclei and
      13.5% +/- 2.0% showed necrotic nuclei. After 10 days in vitro neurons were more
      easily injured by kainate, but the cell death had primarily necrotic
      characteristics. Inhibition of both caspases 1 and 3 significantly reduced the
      apoptotic injury of 3-day old neurons. Neither reduced the necrotic component.
      Inhibition of protein synthesis with cycloheximide was also effective in reducing
      the apoptotic injury without affecting the necrotic injury. Kainate injury causes
      both apoptosis and necrosis, with the injury depending on both the dose of
      kainate and the age of the culture. The apoptotic component can be selectively
      reduced by caspase inhibition or cycloheximide.

PMID- 12500704
TI  - Invariability of the privileged direction of the maximal EMG activity during
      speed-related activation for reaching in the vertical plane.
AB  - Spatial tuning of goal-directed movements is a critical phenomenon for the
      central nervous system. The use of reliable models is a necessary step for the
      understanding of the neural mechanisms governing reaching movements. We analysed
      phasic electromyographic (EMG) activities associated with upper limb reaching
      movements in the vertical plane (12 targets) in seven healthy subjects during
      three successive sessions. We tested the hypothesis that one of the fundamental
      parameters of the directional tuning of phasic EMG activities is the peak of EMG
      activity. To characterize the tuning of phasic EMG activities for the seven
      recorded muscles (brachioradialis, biceps, medial and long head of triceps,
      anterior and posterior deltoid, latissimus dorsi), we digitally compressed the
      EMG activities corresponding to slow reaches to the same targets into the time
      frame of the fast EMG traces. Estimates of gravity-related components were
      subtracted. Peak of EMG activities in the resulting phasic traces were identified
      for each muscle and each target. The maximal peak EMG amongst the 12 peaks of EMG
      activity in the sagittal plane was called M Peak EMG. We defined the directional
      dominance as the ratio of the M Peak EMG divided by the Peak EMG in the opposite
      direction. The M Peak EMG for each muscle was always found in the same privileged
      direction of the movement, except for the latissimus dorsi. The directional
      dominance remained unchanged across recording sessions for the brachioradialis,
      anterior deltoid and posterior deltoid. However, the directional dominance
      increased across sessions for the biceps, medial head of triceps, long head of
      triceps and latissimus dorsi. The invariability of the privileged direction of
      the M peak EMG was thus observed for six of the seven muscles investigated.
      Therefore, we suggest that the selection of the privileged direction of the M
      Peak EMG represents a robust parameter to study the neuromuscular control
      strategy underlying the specification of movement direction.

PMID- 12500705
TI  - Effects of single low dose irradiation on subventricular zone cells in juvenile
      rat brain.
AB  - Although the juvenile human brain is relatively radioresistant, irradiation can
      result in brain growth retardation, progressive mental disturbance, and
      neurologic abnormalities. As neural stem cells or progenitor cells may be a
      target of radiation injury and may play an important role in the brain's
      functional recovery, we examined the effects of whole brain irradiation on these
      cells in juvenile rat. Six-week-old Wistar rats, where the brain is still
      growing, were irradiated with single doses of 1, 2, or 3 Gy X-ray. We measured
      their body and brain weights at 30 or 60 days after irradiation. The
      chronological changes of the subventricular zone (SVZ) were examined at 6 h, 2,
      7, 14, 30, or 60 days after irradiation by immunohistochemistry, specifically
      looking at the neural stem cells or progenitor cells using anti-nestin antibodies
      specific for these cells. The rate of brain weight gain of irradiated rats
      significantly decreased in comparison to controls, although that of body weight
      gain was similar among them. Multiple apoptotic cells appeared in the SVZ at 6 h
      after irradiation with simultaneous reduction in nestin-positive cells (69% of
      the control). The cell levels recovered within a week, with the nestin-positive
      cells reaching maximal numbers (182%) on Day 14. Nestin-positive cells returned
      to baseline levels within 30 days (96%) and remained unchanged for the subsequent
      60 days. The X-ray dosage did not affect these findings. Our findings revealed
      that single low dose X-ray administration reversibly affected the levels of
      neural stem and progenitor cells in the SVZ region. These results suggest that
      continuous multiple administrations of X-rays in clinical treatment may affect
      irreversible changes on neural stem or progenitor cells, causing brain growth
      retardation, or dysfunction.

PMID- 12500706
TI  - Aphasia following left putaminal hemorrhage. Statistical analysis of factors
      affecting prognosis.
AB  - Multivariate and single variable analyses were employed to investigate the
      recovery mode of aphasia in right-handed patients with putaminal hemorrhage on
      the left side. Speech disturbance was evaluated using the standard language test
      for aphasia (SLTA) at intervals of 1, 3 and 6 months after the ictus. Recovery
      was assessed in relation to age, gender, volume and location of hematoma, and
      treatment modalities. Extension of the hematoma into the corona radiata was the
      factor that dominated the prognosis of aphasia at all intervals during the follow
      up period. Good recovery was documented in patients with less than 2 cm2 of the
      hematoma volume located in the corona radiata. Recovery was poor, however, in
      patients with more than 12 cm2 of the hematoma in the corona radiata. While
      aphasia continued to improve over 6 months after the ictus, recovery was more
      prominent in the first 3 months. Our study precisely demonstrated that the
      extension into the corona radiata independently and strongly influenced the
      outcome of aphasia in patients with left putaminal hemorrhage.

PMID- 12500707
TI  - MRI predicts area of increased plasminogen activation in permanent focal cerebral
      ischemia.
AB  - To determine if MRI can predict intracerebral plasminogen activation after focal
      cerebral ischemia (FCI), ischemic regions detected by MRI after 48 h of permanent
      FCI in rats were compared with areas of increased plasminogen activation, defined
      by histological zymography after 72 h of ischemia. The overlap between areas of
      MRI alterations (64.5% +/- 5.4% of total ischemic hemisphere) and areas with
      increased plasminogen activation (62.2% +/- 3.6%) was significant for the
      hemisphere (p < 0.001), the cortex (p < 0.05), and the basal ganglia (p < 0.05).
      Thus, MRI can predict the extent of increased plasminogen activation, which may
      play a role in BBB-mediated post-ischemic brain edema and secondary hemorrhage.

PMID- 12500709
TI  - Functional improvement after motor training is correlated with synaptic
      plasticity in rat thalamus.
AB  - The goals of this study were to determine whether functional outcome after motor
      training in rats was linked to synaptic plasticity in thalamus, and whether the
      Rota-rod apparatus, widely used to test motor function, could be used as an easy
      and quantitative motor skill training procedure. Adult female Sprague-Dawley rats
      (n = 39) were evaluated under three training conditions: 1. Movement requiring
      balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3.
      nontrained controls. Motor function was evaluated by a series of motor tests
      (foot fault placing, parallel bar crossing, rope and ladder climbing) before and
      14 or 28 days after training procedure. Synaptic strength in brain was assessed
      by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained
      animals significantly (p < 0.01) improved motor performance, compared to
      treadmill and nontrained animals. Animals with up to 28 days of simple exercises
      on the treadmill did not show a significantly improved performance on most motor
      tasks, except for an improvement in foot fault placing. Intensive synaptophysin
      immunoreactivity was present in the right but not the left mediodorsal and
      ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and
      in treadmill-trained rats at 28 days. The data suggested that functional outcome
      is effectively improved by motor skill training rather than by simple exercises,
      and this may be related, at least partially, to uniquely lateralized
      synaptogenesis in the thalamus. Both Rota-rod and treadmill could be
      quantitatively used in rats for motor training of different complexity.

PMID- 12500708
TI  - Two surgical cases of internal carotid-ophthalmic artery aneurysms: special
      reference to the usefulness of three-dimensional CT angiography.
AB  - Three-dimensional computerized tomography angiography (3D-CTA) is a noninvasive
      tool for the diagnosis of cerebral aneurysms. 3D-CTA is helpful in the evaluation
      of the configuration of aneurysms and their surrounding vessels and anatomical
      structures. The aim of this study is to assess the usefulness of 3D-CTA for
      patients with unruptured internal carotid-ophthalmic artery aneurysms. We pre
      operatively obtained surgical simulation images using 3D-CTA and 3D
      reconstruction and then compared them with magnetic resonance angiography (MRA),
      conventional cerebral angiography and operative findings in the patients. Two
      patients with unruptured internal carotid-ophthalmic artery aneurysm were
      selected. These patients underwent direct neck clipping after the optic canal was
      unroofed through a combined epidural-subdural approach. The cerebral aneurysm was
      detected by 3D-CTA, MRA and conventional cerebral angiography in each case. Only
      by 3D-CTA, however, could we easily detect the relationships among the aneurysm
      neck, ophthalmic artery and optic canal. Based on this information, direct
      clipping operations were performed safely without any complications. 3D-CTA is an
      excellent noninvasive diagnostic method not only for detecting cerebral
      aneurysms, but also for evaluating the relationships between the aneurysms and
      surrounding structures.

PMID- 12500710
TI  - Obliteration of bilateral dissecting aneurysms of the vertebral arteries
      following repeated subarachnoid hemorrhage: a case report.
AB  - A 51-year-old man presented with loss of consciousness when he underwent
      urological examination at another hospital. CT scans showed subarachnoid
      hemorrhage, and cerebral angiography showed bilateral dissecting aneurysms of the
      vertebral arteries. Following ventricular drainage, the lesion was managed
      conservatively with blood pressure control but again ruptured on day 8. Cerebral
      angiography revealed narrowing of both the dissecting aneurysms. On day 11, the
      right vertebral artery had been spontaneously obliterated and the right
      dissecting aneurysm was filled in a retrograde fashion via the left vertebral
      artery. Proximal occlusion of the right vertebral artery was performed to prevent
      recanalization. Two months later, cerebral angiography revealed that both
      vertebral arteries were obliterated and the basilar artery and right posterior
      inferior cerebellar artery were filled via the right posterior communicating
      artery. The present case demonstrated that the hemodynamic status of bilateral
      dissecting aneurysms of the vertebral artery changed variably indicating the
      necessity of careful angiographic observation.

PMID- 12500712
TI  - The secrets of Dr. Germ.

PMID- 12500711
TI  - Randomized evaluation of adverse events and length-of-stay with routine emergency
      department use of phenytoin or fosphenytoin.
AB  - Intravenous phenytoin has come under increased scrutiny with the introduction of
      the prodrug, fosphenytoin. We evaluated adverse events and length-of-stay using
      parenteral the two drugs in routine emergency department use. Open-label
      randomization of phenytoin or fosphenytoin in 256 Emergency Department patients
      prescribed 279 parenteral doses of a phenytoin-equivalent. All phenytoin was
      administered intravenously, and fosphenytoin was given intravenously or
      intramuscularly (physician preference). Adverse events and Emergency Department
      length-of-stay were recorded; re-presentation to the Emergency Department within
      three months was reviewed for evidence of the purple glove syndrome.
      Nonparametric statistics were used to analyze the data. Seventy-seven patients
      received phenytoin and 202 fosphenytoin; 28 (10.0%) received intramuscular
      fosphenytoin. The mean phenytoin-equivalent dose was similar between the groups.
      Eighteen patients required reduction in infusion rates because of an adverse
      event (phenytoin = 6.5%, fosphenytoin = 6.4%; OR 0.9, 95% CI 0.4 2.6; p = 1.0).
      Adverse events occurred with similar frequency (phenytoin 9.1%, fosphenytoin
      15.8%; OR 0.7, 95% CI 0.3 1.4; p = 0.3). The most common events were: pruritus,
      pain on infusion, and paresthesias. One patient developed hypotension
      (fosphenytoin); there were no other serious adverse events, including phlebitis.
      Median Emergency Department length-of-stay was 6.7 h for phenytoin and 5.7 h for
      fosphenytoin (p = 0.6). In routine Emergency Department use, our data do not
      support formulary conversion from phenytoin to fosphenytoin, based on the
      incidence of adverse events or Emergency Department length-of-stay.

PMID- 12500713
TI  - The nerve gas next door.

PMID- 12500714
TI  - Choosing virginity.

PMID- 12500715
TI  - The battle over abstinence.

PMID- 12500716
TI  - Allergy warning.

PMID- 12500717
TI  - Kneed to know.

PMID- 12500718
TI  - The elephant in the room.

PMID- 12500719
TI  - The inner Einstein.

PMID- 12500720
TI  - How to account for lawyers.

PMID- 12500721
TI  - AIDS epidemic.

PMID- 12500722
TI  - The ghost hunters.

PMID- 12500723
TI  - Not just about sex.

PMID- 12500724
TI  - The melancholy body.

PMID- 12500725
TI  - Sick cruise ships. Cleaning vessels.

PMID- 12500726
TI  - Toddlers in turmoil.

PMID- 12500727
TI  - Health of displaced Albanian Kosovars in the former Yugoslav Republic of
      Macedonia: fitness to travel and health outcomes assessment.
AB  - INTRODUCTION: During the 1999 conflict in Kosovo, an estimated 850,000 people
      were displaced from Kosovo. Many thousands of these people arrived in the Former
      Yugoslav Republic of Macedonia (FYROM), for whom a humanitarian evacuation
      programme (HEP) was conducted by the United Nations High Commissioner for
      Refugees (UNHCR) and the International Organization for Migration (IOM). More
      than 91,000 people were moved to third countries under this programme. METHODS: A
      health assessment tool was designed, validated, and implemented to document the
      health status of the refugees prior to departure. The IOM evaluated 41,652 pre
      travel "fitness to travel" medical assessments for refugees transported by the
      Organization. A colour coding system for fitness-to-travel was used to clearly
      identify refugees to the receiving health authorities according to their health
      condition at the time of departure. RESULTS: A total of 41,652 fitness-to-travel
      assessments were performed between 05 April and 25 June 1999, and were entered
      into a database. There were 21,923 females and 19,566 males. The average age was
      25.3 years (women, 26 years; men, 24.3 years). Of these assessments, 4,647
      (11.2%) individuals who were deemed fit-to-travel required medical assessment at
      the host destination, and of those 1,204 required urgent care. The majority of
      health complaints were acute respiratory tract infections and hypertension.
      CONCLUSIONS: A rapid and efficient system for fitness-to-travel was created to
      assist in the management of health issues related to the urgent and mass movement
      of refugees. The collected health information was of use to health-care planners
      during the crisis and for those responsible for the health-care of newly arrived
      refugees. The lessons learned have implications for future similar operations and
      for the development of research and education programs for both the refugees and
      the host recipient nations.

PMID- 12500728
TI  - Emergency health and risk management in sub-saharan Africa: a lesson from the
      embassy bombings in Tanzania and Kenya.
AB  - In 1998, terrorists simultaneously bombed United States Embassies in Dar es
      Salaam, Tanzania and Nairobi, Kenya. The local response to these bombings was
      unorganized and ad hoc, indicating the need for basic disaster preparedness and
      improvement of emergency management capabilities in both countries. In this
      context, risk and risk management are defined and are related to the health
      hazards affecting Tanzanians and Kenyans. In addition, the growing number of
      injuries in Tanzania is addressed and the relationship between risk management
      and injury is explored. Also, an emergency medicine-based strategy for injury
      control and prevention is proposed. Implications of implementing such a protocol
      in developing nations also are discussed.

PMID- 12500729
TI  - Frail elderly as disaster victims: emergency management strategies.
AB  - PURPOSE: To identify the vulnerabilities of elderly to disasters, and to develop
      strategies to address these vulnerabilities. METHODS: A relevant literature
      search of journal articles, government training materials, news reports, and
      materials from senior organizations was conducted. RESULTS: The vulnerability of
      the elderly to disasters is related to their impaired physical mobility,
      diminished sensory awareness, chronic health conditions, and social and economic
      limitations that prevent adequate preparation for disasters, and hinder their
      adaptability during disasters. Frail elderly, those with serious physical,
      cognitive, economic, and psycho-social problems, are at especially high risk.
      CONCLUSIONS: This segment of the population is growing rapidly. Therefore, it is
      important that emergency management recognize the frail elderly as a special
      needs population, and develop targeted strategies that meet their needs. Several
      management strategies are presented and recommendations for further action are
      proposed.

PMID- 12500730
TI  - Can the "golden hour of shock" safely be extended in blunt polytrauma patients?
      Prospective cohort study at a level I hospital in eastern Switzerland.
AB  - BACKGROUND: The objective was to test, in this trauma system, the North American
      hypothesis that exceeding the 60-minute limit for the entire prehospital time
      ("golden hour of shock") increases mortality of blunt polytrauma patients.
      METHODS: In a prospective, observational, cohort study conducted between 1990 and
      1996, a severity characterization of trauma (ASCOT) score was used to compare the
      actual mortality with the predicted mortality in 107 blunt polytrauma patients
      (Group 1) with prehospital rescue periods < or = 60 minutes (time from accident
      until arrival at the emergency department). The same comparison was performed for
      147 blunt polytrauma patients (Group 2) with rescue periods > 60 minutes.
      Inclusion criteria were blunt trauma of at least two body sites, an Injury
      Severity Score (ISS) of > or = 8, and direct admission to the trauma centre.
      Multivariate regression analysis was performed to test for bias and confounding,
      and to identify factors that might influence mortality. Odd ratio (OR) and 95%
      confidence interval (CI) were calculated. RESULTS: The mortality in Group 1 was
      14%, and was not statistically significantly higher than the 10.2% observed for
      Group 2. 4.8 patients, or 47% more than predicted, died in Group 1 (p = 0.057).
      The corresponding figures in Group 2 were 4.2 patients or 22% fewer than
      predicted (p = 0.19). Multivariate logistic regression confirmed this trend with
      a significant mortality odds ratio of 8 (95% CI 1.7 to 38.5) for Group 1 compared
      to Group 2. Significantly more patients in Group 2 were treated by emergency
      physicians. CONCLUSIONS: It appears in this trauma system, in which emergency
      physicians often are deployed, that the 'golden hour of shock' can be extended
      safely in many blunt polytrauma patients, since this was associated with better
      survival figures than in those patients for whom the time was < 1 hour.

PMID- 12500731
TI  - Psychological distress following urban earthquakes in California.
AB  - During and following a disaster caused by a natural event, human populations are
      thought to be at greater risk of psychological morbidity and mortality directly
      attributable to increased, disaster-induced stress. Drawing both on the research
      of others and that conducted at the Center for Public Health and Disaster Relief
      of the University of California-Los Angeles (UCLA) following California
      earthquakes, this paper examines the extent to which research evidence supports
      these assumptions. Following a brief history of disaster research in the United
      States, the response of persons at the time of an earthquake was examined with
      particular attention to psychological morbidity; the number of deaths that can be
      attributed to cardiovascular events and suicides; and the extent to which and by
      whom, health services are used following an earthquake. The implications of
      research findings for practitioners in the field are discussed.

PMID- 12500732
TI  - Description of ambulance diversions in Edmonton region.

PMID- 12500733
TI  - Resuscitation for patients with out-of-hospital cardiac arrest: Singapore.
AB  - AIM: To evaluate characteristics and outcome of out-of-hospital cardiac arrest
      (OHCA) patients presenting to the Emergency Department (ED), and to examine
      factors that could be used to determine to prolong or abort resuscitation for
      these patients. METHOD: All OHCA patients presenting to the ED were studied over
      a three-month period from November 2001 through January 2002. Patient with
      traumatic cardiac arrest were excluded. Data were collected from the ambulance
      case records, ED resuscitation charts, and the ED Very High Frequency (VHF) radio
      case-log sheet. Information collected included the patient's demographic
      characteristics, timings (time from call to ambulance arrival on scene, time from
      arrival at scene to departure from scene, time from scene to arrival in the ED)
      recorded in the pre-hospital setting, the outcome of the resuscitation, and the
      final outcome for patients who survived ED resuscitation. RESULTS: Ninety-three
      non-traumatic patients with an OHCA were studied during the three-month period.
      Of the 93 patients, 15 (16.1%) survived ED resuscitation, and one survived to
      hospital discharge. There were no statistically significant differences for age,
      race, or gender with regards to the outcome of the resuscitation. The initial
      cardiac rhythms were asystole (65), pulseless electrical activity (21), and
      ventricular fibrillation (7). Fourteen (15%) received bystander cardiopulmonary
      resuscitation (CPR). All seven patients with return of spontaneous circulation
      (ROSC) on arrival in the ED survived ED resuscitation. The ambulance took an
      average of 11.80 +/- 3.36 minutes for the survivors and 11.8 +/- 4.22 minutes for
      the non-survivors from the time of call to get to these patients. The average of
      the scene times was 12.5 +/- 4.61 minutes for the survivors and 12.0 +/- 4.02
      minutes for the non-survivors. Transport time from the scene to the ED took an
      average of 39.1 +/- 8.32 minutes for the survivors and 37.2 +/- 9.00 minutes for
      the non-survivors. CONCLUSION: The survival rate for patients with OHCA after ED
      resuscitation is similar to the results from other studies. There is a need to
      increase the awareness and delivery of basic life support by public education.
      Automatic External Defibrillators (AED) should be available widely to ensure that
      the chance of early defibrillation is increased. Prolonged resuscitation efforts
      appear to be futile for OHCA patients if the time from cardiac arrest until
      arrival in the ED is > or = 30 minutes coupled with no ROSC, and if continuous
      asystole has been documented for > 10 minutes.

PMID- 12500734
TI  - Rapid on-site defibrillation versus community program.
AB  - INTRODUCTION: For patients who suffer out-of-hospital cardiac arrest, the time
      from collapse to initial defibrillation is the single most important factor that
      affects survival to hospital discharge. The purpose of this study was to compare
      the survival rates of cardiac arrest victims within an institution that has a
      rapid defibrillation program with those of its own urban community, tiered EMS
      system. METHODS: A logistic regression analysis of a retrospective data series (n
      = 23) and comparative analysis to a second retrospective data series (n = 724)
      were gathered for the study period September 1994 to September 1999. The first
      data series included all persons at Casino Windsor who suffered a cardiac arrest.
      Data collected included: age, gender, death/survival (neurologically intact
      discharge), presenting rhythm (ventricular fibrillation (VF), ventricular
      tachycardia (VT), or other), time of collapse, time to arrival of security
      personnel, time to initiation of cardiopulmonary resuscitation (CPR) prior to
      defibrillation (when applicable), time to arrival of staff nurse, time to initial
      defibrillation, and time to return of spontaneous circulation (if any).
      Significantly, all arrests within this series were witnessed by the surveillance
      camera systems, allowing time of collapse to be accurately determined rather than
      estimated. These data were compared to those of similar events, times, and
      intervals for all patients in the greater Windsor area who suffered cardiac
      arrest. This second series was based upon the Ontario Prehospital Advanced Life
      Support (OPALS) Study database, as coordinated by the Clinical Epidemiology Unit
      of the Ottawa Hospital, University of Ottawa. RESULTS: The Casino Windsor had 23
      cases of cardiac arrests. Of the cases, 13 (56.5%) were male and 10 (43.5%) were
      female. All cases (100%) were witnessed. The average of the ages was 61.1 years,
      of the time to initial defibrillation was 7.7 minutes, and of the time for EMS to
      reach the patient was 13.3 minutes. The presenting rhythm was VF/VT in 91% of the
      case. Fifteen patients were discharged alive from hospital for a 65% survival
      rate. The Greater Windsor Study area included 668 cases of out-of-hospital
      cardiac arrest: Of these, 410 (61.4%) were male and 258 (38.6%) were female, 365
      (54.6%) were witnessed, and 303 (45.4%) were not witnessed. The initial rhythm
      was VF/VT was in 34.3%. Thirty-seven (5.5%) were discharged alive from the
      hospital. CONCLUSION: This study provides further evidence that PAD Programs may
      enhance cardiac arrest survival rates and should be considered for any venue with
      large numbers of adults as well as areas with difficult medical access.

PMID- 12500735
TI  - Mortality in land-mine accidents in Iran.
AB  - OBJECTIVE: To study the rate of prehospital mortality before establishment of a
      rescue system for victims of land-mines in Iran. METHOD: Survey at rural clinics
      in mine-affected areas, and retrospective review of public patient records.
      RESULTS: A total of 36.4% of casualties from land-mines in the study area died
      during the period of 1989-1999. The mortality seems highest in those victims who
      were torso injured. CONCLUSION: The mortality rate from accidents involving land
      mines in the study area was high. Most fatalities seemingly occurred in the
      prehospital setting.

PMID- 12500736
TI  - Disasters and development: Part I. Relationships between disasters and
      development.
AB  - This module introduces a paradigm for understanding the disaster/development
      interface. Specifically, the module asserts that disasters and development are
      linked closely in that disasters can both destroy development initiatives and
      create development opportunities, and that development schemes can both increase
      and decrease vulnerability. The module consists of four parts: Part One
      introduces these concepts and discusses how disasters can vary from one type of
      hazard to another, as well as from one type of economic condition to another.
      Part Two develops the paradigm in depth, and provides case examples to amplify
      the points made in the text. Part Three describes and discusses different methods
      and tools for analyzing decisions for potential investment of resources, and
      should enhance the reader's capacity to analyze the mitigational benefits of
      development alternatives in both the pre- and post-disaster context. Part Four
      conceptualizes the role of UN agencies, NGOs, and the affected communities in
      promoting development based on the concepts discussed in the module. This
      training module, Disasters and Development, initially was designed to introduce
      this aspect of disaster management to an audience of UN organization
      professionals who form disaster management teams, as well as to government
      counterpart agencies, non-governmental organizations (NGOs), and donors. The
      educational process has been designed to increase the audience's awareness of the
      nature and management of disasters, in order to lead to better performance in
      disaster preparedness and response. The content has been written by experts in
      the field of disaster management and in general follows the UNDP/UNDRO Disaster
      Management Manual and its principles, procedures, and terminology.

PMID- 12500737
TI  - Endoscopic surgery markets offer growth opportunities.

PMID- 12500738
TI  - Hospitals work to improve their security.

PMID- 12500739
TI  - Health care financial officers give their hospitals a mixed diagnosis.

PMID- 12500740
TI  - Analyst: HIPAA compliance proves costly for health care providers.

PMID- 12500742
TI  - Health premiums to jump in 2003.

PMID- 12500741
TI  - Report: federal leadership needed to reduce errors, improve care.

PMID- 12500743
TI  - Price survey. Hospitals move away from IOL (intraocular lens) use.

PMID- 12500744
TI  - Boom, boom, boom. Who has the loudest bang and the most bucks?

PMID- 12500745
TI  - Texas group uses benchmarking to examine productivity. Coding efficiency, other
      factors also reviewed.

PMID- 12500746
TI  - Speak words of health. Providing care to patients with limited English
      proficiency.

PMID- 12500747
TI  - Clean dealing. Legal considerations for buy/sell agreements.
AB  - Buy/sell agreements for medical practices relate as much to governance and power
      as to dollars and cents. A practice should consider strategic, financial and
      legal issues in the buy/sell arrangement and express them in the group's legal
      documents.

PMID- 12500748
TI  - Crisis? What crisis. Five states not experiencing crushing malpractice premium
      increases.
AB  - Five states not experiencing crushing malpractice premium increases. As daily
      headlines across the nation advertise the plight of physicians, medical practices
      and hospitals struggling to cope with soaring medical malpractice costs, five
      states--California, Colorado, Indiana, New Mexico and Wisconsin--have established
      countermeasures that are keeping them on the sidelines of the crisis.

PMID- 12500749
TI  - For love of the profession. Award recipients offer pathways to success.
AB  - What convictions and ambitions drive certain practice leaders--and certain
      organizations--to excel and inspire their practices and their peers? Recipients
      of MGMA and ACMPE's highest honors describe their motivations.

PMID- 12500750
TI  - Psychiatric epidemiology: vibrant art and penetrating science.

PMID- 12500751
TI  - The National Survey of Mental Health and Well-Being in Australia: impact on
      policy.
AB  - OBJECTIVE: To provide a synopsis of the 3-part National Survey of Mental Health
      and Well-Being in Australia and to examine the yield in terms of policy and other
      changes in mental and general health services. METHOD: Published data are
      examined, and a commentary is provided on service-delivery issues that the data
      have revealed. RESULTS: One-year prevalence estimates for the common mental
      disorders, defined according to ICD-10 criteria and assessed using the automated
      version of the Composite International Diagnostic Interview (CIDI-A), have
      indicated rates similar to those of other countries (17.7%). Alarmingly high
      rates were found for alcohol and substance abuse in young persons, especially
      among young men. The number of years of life lost owing to disability
      attributable to mental disorders exceeds the number lost owing to cardiovascular
      disease and cancer. Only 35% of persons with 1 or more of the common mental
      disorders had sought help in the 12 months prior to interview. The point
      prevalence for mental health problems was 14% for persons aged 4 to 17 years. The
      point prevalence for psychotic disorders was 4.7 per 1000. An encouraging finding
      is that 81% of affected individuals had been to their general practitioner (GP)
      in the last year. However, only 20% had participated in any rehabilitation
      program in the past year. CONCLUSIONS: The Survey results are based on a national
      population sample, not on individuals reaching services. They have therefore
      proved to be of great value in influencing policy at federal and state levels and
      may have contributed to increased funding for both services and research.

PMID- 12500752
TI  - Child psychiatric epidemiology and Canadian public policy-making: the state of
      the science and the art of the possible.
AB  - Epidemiological studies have characterized the high burden of suffering that
      child psychiatric disorders cause--14% of children (1.1 million in Canada) have
      clinically important disorders at any given time. In this review, we summarize
      the recent research and discuss several unresolved scientific issues that must be
      addressed to make epidemiology more useful to policy-makers. We then discuss
      implications for policy-making to improve children's mental health outcomes.
      Overall, given the high prevalence rates, increasing clinical services alone will
      not suffice; rather, a multifaceted mix of strategies is required.

PMID- 12500753
TI  - Prevalence and incidence studies of schizophrenic disorders: a systematic review
      of the literature.
AB  - OBJECTIVE: To present the results of a systematic review of the literature
      published between January 1, 1980, and December 31, 2000, that reports findings
      on the prevalence and incidence of schizophrenia and related disorders. METHOD:
      We conducted a literature search of schizophrenia-related epidemiological
      studies, using Medline and HealthSTAR databases and canvassing English-language
      publications. We used a set of predetermined inclusion-exclusion criteria to
      identify relevant studies. Eligible publications were restricted to age ranges of
      18 years and over for prevalence studies and 15 years and over for incidence
      studies. Prevalence and incidence data were extracted and analyzed for
      heterogeneity. RESULTS: A total of 18 prevalence and 8 incidence studies met
      eligibility criteria for the review. Heterogeneity analysis revealed significant
      differences across 1-year and lifetime prevalence and 1-year incidence of
      schizophrenia. The corresponding pooled rates were: 0.34 per 100, 0.55 per 100,
      and 11.1 per 100,000, respectively; the variation in rates between studies was
      generally between 2- and 5-fold. CONCLUSIONS: Although we restricted this review
      to studies using rigorous and relatively homogeneous methods, there remains
      significant heterogeneity of prevalence and incidence rates. This strengthens
      support for the hypothesis that there is real variation in the distribution of
      schizophrenia around the world. Health planners need to have local data on
      schizophrenia rates to improve the accuracy of their interventions, while
      clinicians and researchers need to continue to investigate the etiology of this
      variation.

PMID- 12500754
TI  - Sleep quality in chronic pain patients.
AB  - OBJECTIVE: Chronic pain patients have been reported to complain about poor sleep
      quality. Research aimed at delineating the predictors of poor sleep has produced
      conflicting results. Depressive mood and pain severity are the most frequently
      encountered predictors. This study aimed to find out whether chronic pain
      patients differed from healthy control subjects who had no pain on subjective
      sleep quality measures and, if so, which factors contributed most to poorer sleep
      quality. METHOD: We compared 40 patients with chronic pain who met inclusion
      criteria with 40 healthy control subjects on the measures of sleep quality,
      anxiety, and depression. The predictors of sleep quality were investigated with
      multiple regression in the pain group. RESULTS: Chronic pain patients had higher
      scores than did healthy control subjects on the Beck Anxiety Scale, the Beck
      Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). At the
      bivariate level, pain intensity, anxiety, and depression correlated significantly
      with poorer sleep quality. At the multivariate level, depression was found to be
      the only significant factor correlating with the quality of sleep, and the model
      explained 34% of the variance. CONCLUSIONS: Chronic pain patients suffer from
      poor sleep quality--a function of depressed mood rather than pain intensity,
      duration, or anxiety. However, it is difficult to draw a causal relation in this
      relatively small sample size. Besides, our study sample comprised a mostly
      psychiatric population and may not represent the general group of patients with
      chronic pain.

PMID- 12500755
TI  - Psychiatric disorders and use of mental health services by Ontario women.
AB  - OBJECTIVES: To describe the lifetime prevalence of selected psychiatric disorders
      in Ontario women and to compare these estimates with use of mental health
      resources. METHODS: We obtained data from a survey of 3062 Ontario women, aged 25
      to 74 years, who participated in the Women's Health Study. A 5-item scale
      assessed lifetime prevalence of 5 psychiatric disorders (anxiety, depression,
      posttraumatic stress disorder [PTSD], obsessive-compulsive disorder [OCD], and
      anorexia [AN] or bulimia [BN]). We assessed use of mental health services by
      comorbidity. We employed stratified random sampling to select study subjects.
      Prevalence estimates were weighted and 95%CIs were obtained using Taylor
      linearization techniques (1). RESULTS: Nearly 30% of those surveyed reported at
      least 1 of the disorders studied. The most common were depression (27%) and
      anxiety (21%). Lifetime prevalence of PTSD, OCD, and AN or BN were 10.7%, 6.1%,
      and 3.9%, respectively. Successively younger birth cohorts displayed an increase
      in prevalence and a decrease in onset-age for all disorders. "Ever" use of mental
      health services was higher for women with 3 or more comorbid disorders (65%) than
      for those with no disorder (9.8%), or only 1 disorder (51.4%). CONCLUSIONS: The
      results of this study highlight the need to conduct more research into the
      reasons for the low rates of professional service use, especially for women with
      high comorbidity. They also highlight the need to understand the phenomenon
      underlying the possibly increasing rates of disorders in younger birth cohorts,
      so that outreach strategies can be modified to accommodate differences in younger
      women.

PMID- 12500756
TI  - Counsellors in primary care: benefits and lessons learned.
AB  - OBJECTIVE: To describe a program that integrates mental health counsellors within
      primary care settings, to present data on the program's impact, and to discuss
      lessons learned that may apply in other communities. METHODS: This paper
      describes a Canadian program that brings counsellors and psychiatrists into the
      offices of 87 family physicians in 36 practices in a community of 460,000 in
      Southern Ontario. It describes the goals and organization of the program and the
      activities of counsellors when working in primary care. In addition, it
      summarizes data from the program's evaluation, including demographic data and the
      individual problems seen and services delivered (all from the program's database)
      as well as data on patient outcomes using the General Health Questionnaire (GHQ),
      the Centre for Epidemiological Studies Depression (CESD) Rating Scale, and
      consumer-satisfaction questionnaires. RESULTS: Each counsellor sees an average of
      161 new cases yearly. The major problems are depression, anxiety, and family
      problems. In fact, over 70% of individuals who are seen show significant
      improvements in outcomes. The program has led to a significant increase in access
      to mental health services, a reduction in the use of traditional mental health
      services, high levels of satisfaction with counsellors and family physicians, and
      significant improvements in symptoms and functioning of individuals seen.
      CONCLUSION: This program has effectively integrated counsellors within primary
      care settings, increasing the capacity of primary care to handle mental health
      problems, strengthening links between providers from different sectors, and
      making mental health care more accessible.

PMID- 12500757
TI  - Neuropsychological performance in DSM-IV ADHD subtypes: an exploratory study with
      untreated adolescents.
AB  - OBJECTIVE: To explore neuropsychological performance in untreated Brazilian
      adolescents suffering from attention-deficit hyperactivity disorder (ADHD).
      METHOD: We assessed 30 untreated adolescents with ADHD and 60 healthy control
      subjects, aged 12 to 16 years, using a neuropsychological battery including the
      Wisconsin Card-Sorting Test (WCST), the Stroop Test (ST), the Digit Span, and the
      Word Span. RESULTS: We found neuropsychological differences among the DSM-IV ADHD
      subtypes. Adolescents with the predominantly inattentive subtype (ADHD-I)
      performed more poorly than did control subjects on both the Digit Span and the
      ST. On both the Digit Span and the WCST, adolescents with the combined subtype
      (ADHD-C) presented significantly more impairments than did control subjects.
      Adolescents with the predominantly hyperactive-impulsive type (ADHD-HI) did not
      differ significantly from the control subjects in any measure assessed, but had a
      better performance than did those with ADHD-C on both the Digit Span and the
      WCST. In addition, adolescents with ADHD-HI performed better on the ST than did
      adolescents with ADHD-I. CONCLUSIONS: These findings suggest cognitive
      differences among ADHD subtypes, supporting the diagnostic distinction among
      them. Adolescents with ADHD-HI do not seem to have significant cognitive
      deficits.

PMID- 12500758
TI  - Benefits of switching from typical to atypical antipsychotic medications: a
      longitudinal study in a community-based setting.
AB  - OBJECTIVE: This study examines the clinical and resource utilization effects of
      switching stable outpatients with schizophrenia from a typical to an atypical
      antipsychotic medication. METHOD: We monitored 43 schizophrenia patients from a
      community mental health program who tolerated switching from typical to atypical
      antipsychotic medications. We used the Positive and Negative Syndrome Scale
      (PANSS), Lehman Quality of Life Interview (QOL), and service utilization data for
      2 years before and 2 years after the switch. RESULTS: The switch to atypical
      antipsychotics was associated with significant improvements in positive symptoms,
      in general psychopathology, and in quality of life. Resource requirements,
      including case-management and crisis services and hospitalization days, were
      significantly reduced. We observed no changes in the sample's already low levels
      of negative symptoms. CONCLUSIONS: In stable outpatients with schizophrenia in a
      real-world setting, switching to an atypical antipsychotic can result in
      sustained, significant improvement in clinical response and quality of life, as
      well as in reduced need for hospitalization and community support.

PMID- 12500759
TI  - Homicide in the Canadian Prairies: elderly and nonelderly killings.
AB  - OBJECTIVE: To examine the psychosocial and clinical characteristics of male
      perpetrators of elderly and nonelderly homicides in the Canadian Prairies.
      METHOD: We examined data drawn from a study of 901 adult homicide offenders who
      were incarcerated or on parole between 1988 and 1992 in Alberta, Saskatchewan,
      and Manitoba. RESULTS: Of those studied, 67 men were convicted of homicide
      involving 79 elderly victims, and 671 were convicted of homicide involving 675
      nonelderly victims. Most perpetrators were single and engaged in irregular
      patterns of employment at the time of their index offence. Fourteen (20.8%)
      offenders with elderly victims had a history of psychiatric treatment, compared
      with 98 (14.6%) offenders with nonelderly victims; however, this difference was
      not statistically significant. Approximately 30% of both groups were diagnosed
      with personality disorders. A comparison of the index- offence characteristics
      showed no significant differences between the 2 groups. CONCLUSION: Our findings
      suggest that elderly individuals are more likely to be killed in their own homes
      by strangers. Social isolation appears to be a significant risk factor in cases
      of elderly homicide.

PMID- 12500760
TI  - Categorizing continuous variables.

PMID- 12500761
TI  - A case of neuroleptic malignant syndrome with clozapine and risperidone.

PMID- 12500762
TI  - Zonisamide treatment of bipolar disorder: a case report.

PMID- 12500763
TI  - Combined use of atypical antipsychotics and cognitive-behavioural therapy in
      schizophrenia.

PMID- 12500764
TI  - Distress levels in patients with premenstrual dysphoric disorder.

PMID- 12500765
TI  - Alcoholism, seasonal depression, and suicidal behaviour.

PMID- 12500766
TI  - Recruiting residents through a summer medical student program.

PMID- 12500767
TI  - A case of paroxetine-induced galactorrhea.

PMID- 12500768
TI  - Beyond principal-component analysis of the positive and negative syndrome scale
      in patients with schizophrenia.

PMID- 12500769
TI  - Olanzapine-induced hair loss.

PMID- 12500770
TI  - Paternal age as a risk factor.

PMID- 12500771
TI  - Geriatric nephrology and urology literature.

PMID- 12500772
TI  - Drug therapy in the official Danish plague instructions, 1619-1709.

PMID- 12500773
TI  - Poisoning the spindle: serendipity and discovery of the anti-tumor properties of
      the Vinca alkaloids (Part II).

PMID- 12500774
TI  - A hospital pharmacy in 1924.

PMID- 12500775
TI  - The Norwegian translation of the Francis Scale of Attitude toward Christianity.
AB  - This paper reviews the development of the Francis Scale of Attitude toward
      Christianity and then examines the psychometric properties of the Norwegian
      translation of this instrument among a sample of 479 young people between the
      ages of 11 and 18 years attending secondary school. The data support the
      reliability of this instrument and commend it for further validation studies and
      for wider general use among young people in Norway.

PMID- 12500776
TI  - Inducing and reducing false memories: a Swedish version of the Deese-Roediger
      McDermott paradigm.
AB  - Participants tend to falsely remember a nonpresented critical word after having
      studied a list of the word's primary associates. We present here a Swedish
      version of the Deese-Roediger-McDermott paradigm, which provides a tractable
      method of experimentally inducing and investigating such illusory memories. In
      Experiment 1 it was demonstrated that the constructed stimulus material induced
      highly reliable false-recall and false-recognition effects, and, moreover, that
      veridical and false memories were associated with a similar phenomenological
      experience of remembering. The results from Experiment 2 indicated that the
      susceptibility to false recognition can be substantially reduced when
      participants are explicitly required to monitor the sources of their memories.
      These findings are consistent with predictions derived from the source-monitoring
      framework.

PMID- 12500777
TI  - Everyday value conflicts and integrative complexity of thought.
AB  - This study examined the value pluralism model in everyday value conflicts, and
      the effect of issue context on complexity of thought. According to the cognitive
      manager model we hypothesized that respondents would obtain a higher level of
      integrative complexity on personal issues that on professional and general
      issues. We also explored the relations of integrative complexity to value
      priorities, measured by the Schwartz Value Survey, and to emotional empathy. The
      value pluralism model was not supported by the data collected from 126 university
      students from social science, business and technology. The cognitive manager
      model was partially confirmed by data from females but not from males. Concerning
      value priorities, more complex respondents had higher regard for self
      transcendence values, and less complex respondents for self-enhancement values
      Emotional empathy was also significantly related to complexity score.

PMID- 12500778
TI  - Relationships between exposure to bullying at work and psychological and
      psychosomatic health complaints: the role of state negative affectivity and
      generalized self-efficacy.
AB  - The aim of this study was to investigate the relationships between exposure to
      behaviors identified as workplace bullying and self-report measurements of
      psychological and psychosomatic health complaints. Secondly, we investigated
      whether these relationships were mediated by the state negative affectivity of
      the victim. Thirdly, we investigated the extent to which generalized self
      efficacy moderated the relationships between exposure to bullying behaviors and
      health complaints. Two hundred and twenty-four white- and blue-collar employees
      from a Danish manufacturing company participated in the study. Exposure to
      bullying behaviors was associated with an increase in psychological health
      complaints, increased levels of psychosomatic complaints and an elevated level of
      state negative affectivity. Whereas bullying by itself accounted for 27% of the
      variance in psychological health complaints and 10% of the variance in
      psychosomatic complaints, the results pointed to state negative affectivity as a
      partial mediator of the relationships between exposure to bullying behaviors and
      both measures of self-reported health. Though not directly related to reported
      exposure to bullying behaviors, generalized self-efficacy seemed to act as a
      moderator of the relationship between exposure to bullying behaviors and
      psychological health complaints.

PMID- 12500779
TI  - Ability to take an out-group's perspective in explaining positive and negative
      behaviors.
AB  - A total of 251 Latvian and Russian schoolteachers explained positive and negative
      behaviours from their own perspective and from the perspective of an ethnic out
      group. The results were in line with the attributional pattern usually found in
      studies using Hewstone's direct perspective of judgement, when participants are
      asked to take the perspective of an ethnic out-group. That is, there was an
      outcome effect in causal attributions for in-group actors and a categorization
      effect for negative behaviour from the imagined (out-group's) perspective. The
      attributions from the direct perspective only partly replicated the commonly
      found pattern. The results support Montgomery's perspective theory.

PMID- 12500780
TI  - Dichotic listening and sleep deprivation: vigilance effects.
AB  - Twelve sleep-deprived and 13 non-deprived Navy cadets were tested with the
      dichotic listening procedure for effects of sleep deprivation on hemispheric
      asymmetry and sustained attention. Consonant-vowel syllables were presented to
      the subjects in three different conditions, a divided (non-forced) attention
      condition, a forced right ear and a forced left ear attention condition. In the
      two forced attention conditions the subjects were instructed to focus attention
      only on the right or left ear stimulus. The results showed an expected right ear
      advantage for both groups during the non-forced and forced right attention
      conditions, indicating superior left hemisphere processing. During the forced
      left attention condition, the sleep-deprived subjects showed no ear advantage at
      all, while the non-deprived subjects showed an expected left ear advantage. The
      results are discussed within a theoretical framework of a dual process model,
      where sleep deprivation disrupts the ability to sustain attention, caused by a
      temporary failure of the right hemisphere's top-down (instruction-driven)
      processing to override the left hemisphere's bottom-up (stimulus-driven)
      processing.

PMID- 12500781
TI  - Age as a modifier of sexually aggressive attitudes in men.
AB  - Male attitudes and behaviours related to imagined sexual aggression were
      investigated in 99 Finnish men (mean age 24.3 years). Structural equation
      modelling suggested that imagined sexual aggression was directly predicted by
      hostile masculine ideologies and past antisocial acts, and indirectly by subject
      age (hostile masculinity decreased with age). For more detailed analyses of age
      effects on attitudes, the subjects were split into an older and a younger group.
      A small group of incarcerated rapists (n = 8; mean age 33.4 years) was included
      for comparative purposes; these were similar in age to the older group (n = 34;
      mean age 31.5 years) and were given the same attitude items. The younger men and
      the rapists expressed significantly more hostility toward women and acceptance of
      rape myths, and had a higher likelihood of committing rape than older men.
      Although younger men accepted interpersonal violence and sexual dominance, their
      attitudes were not necessarily reflected in past sexually aggressive behaviours,
      as they were in the rapists who differed from the younger men mainly in terms of
      their past antisocial activities.

PMID- 12500782
TI  - Psychological characteristics of elderly insomniacs.
AB  - Sixty insomniacs, aged 60 years or over, fulfilling the DSM-IV criteria for
      primary insomnia, completed a set of questionnaires measuring psychological
      distress. These included the Sleep Impairment Index (SIM), the Symptom Check List
      90-Revised (SCL-90-R), the Penn State Worry Questionnaire (PSWQ), the Toronto
      Alexithymia Scale-20 (TAS-20) and the Elders Life Stress Inventory (ELSI). The
      insomniacs were compared on these measures with two contrast groups, one of
      elderly good sleepers and one an elderly community sample. As norms were
      developed for the SCL-90-R and PSWQ, insomniacs were also contrasted with the
      norm groups on these measures. In general, the results indicated a higher level
      of psychological distress among insomniacs than among the good sleepers, while
      there were negligible differences between insomniacs and the community sample on
      most measures. Overall, elderly insomniacs scored higher on measures of worry
      compared with the other groups, followed by measures of somatization, obsessive
      compulsion and depression. It is concluded that excessive worrying was the most
      characteristic feature of elderly insomniacs.

PMID- 12500783
TI  - Automatic mimicry reactions as related to differences in emotional empathy.
AB  - The hypotheses of this investigation were derived by conceiving of automatic
      mimicking as a component of emotional empathy. Differences between subjects high
      and low in emotional empathy were investigated. The parameters compared were
      facial mimicry reactions, as represented by electromyographic (EMG) activity when
      subjects were exposed to pictures of angry or happy faces, and the degree of
      correspondence between subjects' facial EMG reactions and their self-reported
      feelings. The comparisons were made at different stimulus exposure times in order
      to elicit reactions at different levels of information processing. The high
      empathy subjects were found to have a higher degree of mimicking behavior than
      the low-empathy subjects, a difference that emerged at short exposure times (17
      40 ms) that represented automatic reactions. The low-empathy subjects tended
      already at short exposure times (17-40 ms) to show inverse zygomaticus muscle
      reactions, namely "smiling" when exposed to an angry face. The high-empathy group
      was characterized by a significantly higher correspondence between facial
      expressions and self-reported feelings. No differences were found between the
      high- and low-empathy subjects in their verbally reported feelings when presented
      a happy or an angry face. Thus, the differences between the groups in emotional
      empathy appeared to be related to differences in automatic somatic reactions to
      facial stimuli rather than to differences in their conscious interpretation of
      the emotional situation.

PMID- 12500784
TI  - Online group interaction and mental health: an analysis of three online
      discussion forums.
AB  - The present study examined interactions on three Norwegian online discussion
      forums, and attempted to identify differences in interactions and plausible
      outcomes of thematically dissimilar forums. Four categories were applied to the
      forums in order to distinguish potentially constructive and destructive uses.
      Interaction along the constructive-destructive dimension was contingent upon the
      themes discussed, as well as the level and nature of professional involvement.
      Interaction adhering to a destructive dimension was identified only in relation
      to the forum for eating disorders. Discovering to what extent theme and
      professional involvement influence interactions in discussion forums might guide
      further professional involvement in online group settings and the design of
      appropriate online environments.

PMID- 12500785
TI  - Biomechanical analysis of Maxwell-Brancheau arthroereisis implants.
AB  - The Maxwell-Brancheau arthroereisis (MBA) implant is currently used in treating
      flexible flatfoot deformities in children and adults. However, no guidelines have
      been established to determine the degree of correction with the five different
      MBA implant sizes (6-, 8-, 9-, 10-, and 12-mm diameters). A biomechanical
      analysis of these implants was performed in fresh-frozen cadaver limbs to
      quantitate the effects on subtalar joint (STJ) motion restriction and
      radiographic angles. This study found a restriction of subtalar joint range of
      motion that ranged from 32.0 +/- 5.4%, 44.8 +/- 7.7%, 59.0 +/- 7.2%, 65.5 +/-
      8.7%, and 76.8 +/- 7.6% restriction with successively larger sized implants
      respectively (p < .001). Repeated measures analysis of variance (ANOVA) revealed
      alterations in the first intermetatarsal, lateral talo-first metatarsal, talar
      declination, calcaneal inclination, and first metatarsal declination angles with
      successively larger implant use. Analysis of the dorsal talo-first metatarsal,
      talo-second metatarsal, lateral talocalcaneal angles, and first to fifth
      metatarsal head splay showed no changes as implant size was altered. The study
      also attempted to assess the effects on the tendo Achillis when the subtalar
      joint was changed from a pronated to a supinated position. The observations
      showed a 6.33 +/- 1.40% (p = .001) increase in tendon length which suggests
      increased tension to the tendon. These findings can aid the surgeon in selection
      of the MBA implant size based on the desired amount of subtalar joint motion
      restriction. In turn, this may reduce errors in the correction of flexible
      flatfoot with the MBA implant.

PMID- 12500786
TI  - Biomechanical abnormalities and ulcers of the great toe in patients with
      diabetes.
AB  - A prospective analysis was conducted to identify structural and biomechanical
      first ray abnormalities in consecutive diabetic patients presenting with their
      first great toe ulcer. Twenty-six patients (33 feet) met the inclusion criteria,
      with seven patients having bilateral hallux ulcers. There was no other history of
      ulcer, trauma, or surgery on the respective limb. Data were obtained during the
      patients' initial presentation with a great toe ulcer and included verbal
      history, standardized weight bearing radiographs, and standardized objective
      clinical measurements. Four patients (four feet) with subungual ulcers were
      included because of mechanical etiology. Twenty-four of the remaining 29 involved
      limbs exhibited gastrocnemius/soleus equinus and two other limbs had
      gastrocnemius equinus. Twenty-eight of 29 had structural hallux limitus. Twenty
      four had hallux interphalangeal abductus. Twenty of the 33 ulcers were located
      plantar-medially at the interphalangeal joint area. Other frequent findings were
      first ray elevatus or dorsiflexion deformity (18 of 29), functional hallux
      limitus (14 of 29), interphalangeal joint sesamoid bone (13 of 29), hyperextended
      interphalangeal joint (13 of 29), and a prominent plantar-medial condyle of the
      proximalaspect of the distalphalanx (7 of 29). Halluxmalleus was less common (4
      of 29), but consistently associated with plantar-distal tip ulceration.
      Metatarsus primus adductus was also infrequent (6 of 29). This study identifies
      and illustrates the importance of several biomechanical and structural factors
      present on initial presentation of great toe ulcers. Addressing these factors may
      improve the success of treatment and lessen the occurrence of this common and
      complex problem.

PMID- 12500787
TI  - Lateral column symptomatology following plantar fascial release: a prospective
      study.
AB  - Plantar fasciitis or heel spur syndrome usually resolves with conservative
      management, but for patients with continued pain, surgical intervention is often
      pursued. In some cases, plantar fasciitis is relieved, but pain in the lateral
      column area appears postoperatively. This lateral column pain may be debilitating
      for the patient and often overlooked by the foot and ankle surgeon. The goal of
      the study was to identify the maximum amount of plantar fascia that can be
      surgically released to treat recalcitrant heel pain effectively while preventing
      the development of lateral column symptoms. All patients undergoing plantar
      fasciotomy after failing conservative treatment were eligible to participate.
      Patients rated their pain with an 11-point (0-10) visual analog scale (VAS) and
      described its location prior to and at monthly intervals after their surgery.
      Surgeons recorded whether 25, 50, or 66% of the plantar fascia was released
      during surgery. Open procedures were performed 72% of the time, and
      endoscopically in 28% of the patients. Key outcome variables included degree of
      fascial release and foot structure. Patients (n = 47) with lateral column pain
      after surgery (n = 15 feet) had a mean +/- S.E. of 60.6 +/- 3.0% of their plantar
      fascia released while those without pain (n = 35 feet) had only 48.7 +/- 1.9% of
      this fascia released during surgery (ANOVA, p = .019). Age, weight, body mass
      index, gender, smoking status, comorbidities, general health, surgical procedure,
      postoperative care, calcaneal inclination angle, and talar declination angle did
      not differ for these groups (p > .146). For this patient population, regardless
      of surgical technique (endoscopic or open release), lateral column symptoms were
      more likely to result when more than 50% of the plantar fascia was released. The
      report proposes that a maximum of 50% of the plantar fascia be released during
      surgery.

PMID- 12500788
TI  - Ainhum (dactylolysis spontanea): a radiological survey of 6000 patients.
AB  - Dactylolysis spontanea is an idiopathic condition affecting the fifth toe, and
      sometimes other toes, that is frequently bilateral, with lesions in different
      stages. Between 1977 and 1999, a total 6000 radiographic studies of the feet were
      reviewed in a mainly African American population in Chicago, Illinois. After an
      initial screening based on the Cole criteria, 581 patients were selected and re
      examined, and amplification techniques were performed. After reviewing the
      complementary exams, 102 patients were diagnosed with dactylolysis spontanea or
      ainhum. Soft-tissue constriction was the most frequently presented radiological
      sign on the initial screening. Kurtosis at the digit plantar fold and marked
      rotation of the fifth toe were normal findings in asymptomatic patients.
      Demographics, comorbidities, and radiological findings were analyzed in the
      selected population. Associated diseases occurring in these patients appeared to
      have no specific etiologic correlation with ainhum. African Americans and the
      dark-skinned population are affected exclusively by this condition, presumably
      due to the fibrogenic tendency of these individuals. Early diagnosis and accurate
      staging of ainhum are facilitated by radiological examination of the feet. The
      findings suggest that this condition is underdiagnosed and overlooked because its
      low prevalence and variable clinical presentations that might mimic more common
      etiologies, including localized trauma.

PMID- 12500789
TI  - Mechanical characteristics of an absorbable copolymer internal fixation pin.
AB  - Absorbable internal fixation is gaining acceptance among foot and ankle surgeons.
      While absorbable pins made of poly-L-lactic acid, polyglycolic acid, or poly-p
      dioxanone are generally effective as applied in the foot, their strength loss
      profiles and degradation characteristics may not be optimally matched to the
      healing process. This study investigated a novel absorbable oriented copolymer
      pin, with unique absorption characteristics, made of 82% poly-L-lactic acid and
      18% polyglycolic acid, to determine its suitability for use in fixation in the
      foot. The pins were incubated in a 37 degrees C buffer bath that simulated in
      vivo conditions and were mechanically tested in four-point bend and shear at time
      intervals up to 12 weeks. In vitro strength loss profiles demonstrated peak
      strength retention (flexural and shear) for about 8 weeks, with 50% of properties
      remaining by 12 weeks. The initial Young's modulus of the pins was approximately
      7 GPa. The mathematical relationship between pin strength and pin diameter was
      discussed, providing the surgeon with helpful criteria for making an implant
      selection. The degradation time course of these pins appears to compliment the
      known healing dynamics of bone, making them a suitable choice for use in foot
      surgery.

PMID- 12500790
TI  - Evaluation of the anterior and middle talocalcaneal articular facets and the
      Evans osteotomy.
AB  - The purpose of this study was to determine the occurrence of discrete anterior
      and middle talocalcaneal facets and the distance of these facets from the
      anterior border of the calcaneus as it relates to the Evans osteotomy. Seven
      hundred sixty-eight calcanei were examined from the human osteology archive at
      the Cleveland Museum of Natural History. Measurements taken included: 1) distance
      from the proximal border of the anterior facet to the anterior border of the
      calcaneus (DTAF), 2) distance from the distal border of the middle facet to the
      anterior border of the calcaneus (DTMF), and 3) width of facet separation (WFS).
      The results revealed that 310 of 755 (41.06%) had discrete anterior and middle
      facets and 423 of 755 (56.03%) had a conjoined facet. In those with discrete
      facets, the mean DTAF, DTMF, and WFS were 11.04 mm, 15.47 mm, and 3.85 mm,
      respectively. In those with discrete facets, an osteotomy begun between 11.5 mm
      and 15 mm from the calcaneocuboid joint should pass between the anterior and
      middle facets and avoid damaging these articular surfaces. This information may
      aid the foot and ankle surgeon in patient selection and in attaining optimal
      surgical outcome for the Evans lateral column lengthening procedure.

PMID- 12500791
TI  - The footprint ratio as a predictor of pes planus: a study of indigenous
      Malawians.
AB  - The footprint ratio or arch index is the ratio of the middle third of the toeless
      footprint to the total toeless footprint area. This ratio was determined in an
      indigenous Malawian population to classify the foot arch type and the incidence
      of pes planus. The dynamic footprints of 305 able-bodied subjects, free from foot
      pain, comprising 139 males and 166 females aged between 13 and 17 years, were
      studied from randomly selected secondary schools in the city of Blantyre. Males
      had higher arch index than female, but this was not statistically significant (p
      > .5). The incidence of pes planus was 242.6/1000 using the arch index method.
      This incidence was higher when it was compared to other methods. Furthermore, the
      index was found to be statistically higher in Malawians than Caucasian Americans
      (p < .001) and Europeans (p < .01) previously studied using similar methods. The
      study has shown probably for the first time the arch index of an African
      population, and it shows racial variations between Caucasians and Africans. Also
      the reliability and reproducibility of the arch index method in determining the
      incidence of pes planus in a given population has been confirmed.

PMID- 12500792
TI  - Intraosseous lipoma of the calcaneus: a review and report of four cases.
AB  - Intraosseous lipomas have been reported as rare tumors in the lower extremity.
      They have been identified in the tibia, fibula, metatarsals, and calcaneus. They
      are frequently misdiagnosed as other tumors, especially unicameral bone cysts or
      aneutysmal bone cysts when found within the calcaneus. A detailed description of
      intraosseous calcaneal lipomas and their treatment is given. Surgical technique
      and four case reports are presented. One of the cases involved a pathologic
      calcaneal fracture, a finding to the authors' knowledge that has not been
      previously reported.

PMID- 12500793
TI  - A new distraction method in difficult ankle arthroscopy.

PMID- 12500794
TI  - A new technique for cylindrical peg-in-hole arthrodesis of the interphalangeal
      joint.

PMID- 12500795
TI  - Military and non-military use of depleted uranium.

PMID- 12500796
TI  - What ICRP advice applies to DU? International Commission on Radiological
      Protection.

PMID- 12500797
TI  - Properties, use and health effects of depleted uranium (DU): a general overview.
AB  - Depleted uranium (DU), a waste product of uranium enrichment, has several
      civilian and military applications. It was used as armor-piercing ammunition in
      international military conflicts and was claimed to contribute to health
      problems, known as the Gulf War Syndrome and recently as the Balkan Syndrome.
      This led to renewed efforts to assess the environmental consequences and the
      health impact of the use of DU. The radiological and chemical properties of DU
      can be compared to those of natural uranium, which is ubiquitously present in
      soil at a typical concentration of 3 mg/kg. Natural uranium has the same
      chemotoxicity, but its radiotoxicity is 60% higher. Due to the low specific
      radioactivity and the dominance of alpha-radiation no acute risk is attributed to
      external exposure to DU. The major risk is DU dust, generated when DU ammunition
      hits hard targets. Depending on aerosol speciation, inhalation may lead to a
      protracted exposure of the lung and other organs. After deposition on the ground,
      resuspension can take place if the DU containing particle size is sufficiently
      small. However, transfer to drinking water or locally produced food has little
      potential to lead to significant exposures to DU. Since poor solubility of
      uranium compounds and lack of information on speciation precludes the use of
      radioecological models for exposure assessment, biomonitoring has to be used for
      assessing exposed persons. Urine, feces, hair and nails record recent exposures
      to DU. With the exception of crews of military vehicles having been hit by DU
      penetrators, no body burdens above the range of values for natural uranium have
      been found. Therefore, observable health effects are not expected and residual
      cancer risk estimates have to be based on theoretical considerations. They appear
      to be very minor for all post-conflict situations, i.e. a fraction of those
      expected from natural radiation.

PMID- 12500798
TI  - Civil use of depleted uranium.
AB  - In this paper the civilian exploitation of depleted uranium is briefly reviewed.
      Different scenarios relevant to its use are discussed in terms of radiation
      exposure for workers and the general public. The case of the aircraft accident
      which occurred in Amsterdam in 1992 involving a fire, is discussed in terms of
      the radiological exposure to bystanders. All information given has been obtained
      on the basis of an extensive literature search and are not based on measurements
      performed at the Institute for Transuranium Elements.

PMID- 12500799
TI  - Isotopic composition and origin of uranium and plutonium in selected soil samples
      collected in Kosovo.
AB  - Soil samples collected from locations in Kosovo where depleted uranium (DU)
      ammunition was expended during the 1999 Balkan conflict were analysed for uranium
      and plutonium isotopes content (234U, 235U, 236U, 238U, 238Pu, (239 + 240)Pu).
      The analyses were conducted using gamma spectrometry (235U, 238U), alpha
      spectrometry (238Pu, (239 + 240)Pu), inductively coupled plasma-mass spectrometry
      (ICP-MS) (234U, 235U, 236U, 238U) and accelerator mass spectrometry (AMS)
      (236U)). The results indicated that whenever the U concentration exceeded the
      normal environmental values (approximately 2 to 3 mg/kg) the increase was due to
      DU contamination. 236U was also present in the released DU at a constant ratio of
      236U (mg/kg)/238U (mg/kg) = 2.6 x 10(-5), indicating that the DU used in the
      ammunition was from a batch that had been irradiated and then reprocessed. The
      plutonium concentration in the soil (undisturbed) was about 1 Bq/kg and, on the
      basis of the measured 238Pu/(239 + 240)Pu, could be entirely attributed to the
      fallout of the nuclear weapon tests of the 1960s (no appreciable contribution
      from DU).

PMID- 12500800
TI  - Characterisation of projectiles composed of depleted uranium.
AB  - Projectiles suspected to be composed of depleted uranium (DU) were found in
      Kosovo. Their properties were analysed using alpha and gamma ray spectrometry,
      mass spectrometry and electron microscopy. They were found to be composed of DU
      with small amounts of other elements such as Ti. 236U was detected in the
      penetrators, reflecting the use of reprocessed fuel. No transuranium elements
      were detected. The typical external dose rate meter is not the best option for
      mapping the location of penetrators from the ground. Monte Carlo calculations
      were performed in estimating possible skin doses. Penetrators in long-lasting
      contact with skin may cause a notable equivalent dose to skin.

PMID- 12500801
TI  - Depleted uranium particles in selected Kosovo samples.
AB  - Selected soil samples, collected in Kosovo locations where DU ammunition was
      expended during the 1999 Balkan conflict, have been investigated by secondary ion
      mass spectrometry (SIMS), X-ray fluorescence imaging using a micro-beam (micro
      XRF) and scanning electron microscopy equipped with an energy dispersive X-ray
      fluorescence detector (SEM-EDXRF), with the objective to test the suitability of
      these techniques to identify the presence of small DU particles and measure their
      size distribution and the 235U/238U isotopic ratio (SIMS). Although the results
      do not permit any legitimate extrapolation to all the sites hit by the DU rounds
      used during the conflict, they indicated that there can be "spots ' where
      hundreds of thousands of particles may be present in a few milligrams of DU
      contaminated soil. The particle size distribution showed that most of the DU
      particles were <5 microm in diameter and more than 50% of the particles had a
      diameter <1.5 microm. Knowledge on DU particles is needed as a basis for the
      assessment of the potential environmental and health impacts of military use of
      DU, since it provides information on possible re-suspension and inhalation.

PMID- 12500802
TI  - Actinide analysis of a depleted uranium penetrator from a 1999 target site in
      southern Serbia.
AB  - Following the detection of 236U in depleted uranium (DU) ammunition used during
      the Balkans conflict in the 1990s, concern has been expressed about the
      possibility that other nuclides from the nuclear fuel cycle and, in particular,
      transuranium nuclides, might be present in this type of ammunition. In this
      paper, we report the results of uranium and plutonium analyses carried out on a
      depleted uranium penetrator recovered from a target site in southern Serbia. Our
      data show the depleted nature of the uranium and confirm the presence of trace
      amounts of plutonium in the penetrator. The activity concentration of
      (239+240)PU, at 45.4+/-0.7 Bq kg(-1), is the highest reported to date for any
      penetrator recovered from the Balkans. This concentration, however, is comparable
      to that expected to be present naturally in uranium ores and, from a radiological
      perspective, would only give rise to a very small increase in dose to exposed
      persons compared to that from the DU itself.

PMID- 12500803
TI  - Oxidation states of uranium in DU particles from Kosovo.
AB  - The oxidation states of uranium contained in depleted uranium (DU) particles were
      determined by synchrotron radiation based micro-XANES, applied to individual
      particles in soil samples collected at Ceja Mountain, Kosovo. Based on scanning
      electron microscopy (SEM) with XRMA prior to micro-XANES, DU particles ranging
      from submicrons to about 30 microm (average size: 2 microm or less) were
      identified. Compared to well-defined standards, all investigated DU particles
      were oxidized. About 50% of the DU particles were characterized as UO2, the
      remaining DU particles present were U3O8 or a mixture of oxidized forms (ca. 2/3
      UO2, 1/3 U3O8). Since the particle weathering rate is expected to be higher for
      U3O8 than for UO2, the presence of respiratory U3O8 and UO2 particles, their
      corresponding weathering rates and subsequent remobilisation of U from DU
      particles should be included in the environmental or health impact assessments.

PMID- 12500804
TI  - Uranium ores and depleted uranium in the environment, with a reference to uranium
      in the biosphere from the Erzgebirge/Sachsen, Germany.
AB  - The Erzgebirge ('Ore Mountains') area in the eastern part of Germany was a major
      source of uranium for Soviet nuclear programs between 1945 and 1989. During this
      time, the former German Democratic Republic became the third largest uranium
      producer in the world. The high abundance of uranium in the geological formations
      of the Erzgebirge are mirrored in the discovery of uranium by M. Klaproth close
      to Freiberg City in 1789 and the description of the so-called 'Schneeberg'
      disease, lung cancer caused in miners by the accumulation of the uranium decay
      product, radon, in the subsurfaces of shafts. Since 1991, remediation and
      mitigation of uranium at production facilities, rock piles and mill tailings has
      taken place. In parallel, efforts were initiated to assess the likely adverse
      effects of uranium mining to humans. The costs of these activities amount to
      about 6.5 10(9) Euro. A comparison with concentrations of depleted uranium at
      certain sites is given.

PMID- 12500805
TI  - Use of HPGe gamma-ray spectrometry to assess the isotopic compositiion of uranium
      in soils.
AB  - Gamma-ray spectrometry was used to determine uranium activity and investigate the
      presence of depleted uranium in soil samples collected from camping sites of the
      Greek expeditionary force in Kosovo. Assessment of 238U concentrations was based
      on measurements of the 63.3 keV and 92.38 keV emissions of its first daughter
      nuclide, 234Th. To determine the isotopic ratio of 238U/235U, secular equilibrium
      along the two radioactive series was first ensured and thereby the contribution
      of 235U under the 186 keV peak was deduced. The uranium activity in the samples
      varied from 48 to 112 Bq kg(-1), whereas the activity ratio of 238U/235U averaged
      23.1+/-4.3.

PMID- 12500806
TI  - The biokinetics of uranium migrating from embedded DU fragments.
AB  - Military uses of depleted uranium (DU) munitions have resulted in casualties with
      embedded DU fragments. Assessment of radiological or chemical health risks from
      these fragments requires a model relating urinary U to the rate of migration of U
      from the fragments, and its accumulation in systemic tissues. A detailed
      biokinetic model for U has been published by the International Commission on
      Radiological Protection (ICRP), but its applicability to U migrating from
      embedded DU fragments is uncertain. Recently, Pellmar and colleagues (1999)
      conducted a study at the Armed Forces Radiobiology Research Institute (AFRRI) on
      the redistribution and toxicology of U in rats with implanted DU pellets,
      simulating embedded fragments. This paper compares the biokinetic data from that
      study with the behavior of commonly studied forms of U in rats (e.g.,
      intravenously injected U nitrate). The comparisons indicate that the biokinetics
      of U migrating from embedded DU is similar to that of commonly studied forms of U
      with regard to long-term accumulation in kidneys, bone, and liver. The results
      provide limited support for the application of the ICRP's model to persons with
      embedded DU fragments. Additional information is needed with regard to the short
      term behavior of migrating U and its accumulation in lymph nodes, brain,
      testicles, and other infrequently studied U repositories.

PMID- 12500807
TI  - Military use of depleted uranium: assessment of prolonged population exposure.
AB  - This work is an exposure assessment for a population living in an area
      contaminated by the use of depleted uranium (DU) weapons. RESRAD 5.91 code was
      used to evaluate the average effective dose at depths of 1, 10, 20 cm of
      contaminated soil, in a residential farming scenario. Critical pathways and
      groups are identified in soil inhalation and ingestion; critical group is
      identified in children playing with the soil. From the available information on
      DU released at targeted sites, both critical and average exposure can produce
      toxicological hazards. The annual dose limit for the population can be exceeded
      within a few years from DU deposition for soil inhalation. As a result, clean up
      at targeted sites must be planned on the basis of measured concentration, when
      available, while special measures must be adopted anyway to reduce unaware
      exposures.

PMID- 12500808
TI  - Depleted uranium residual radiological risk assessment for Kosovo sites.
AB  - During the recent conflict in Yugoslavia, depleted uranium rounds were employed
      and were left in the battlefield. Health concern is related to the risk arising
      from contamination of areas in Kosovo with depleted uranium penetrators and dust.
      Although chemical toxicity is the most significant health risk related to
      uranium, radiation exposure has been allegedly related to cancers among veterans
      of the Balkan conflict. Uranium munitions are considered to be a source of
      radiological contamination of the environment. Based on measurements and
      estimates from the recent Balkan Task Force UNEP mission in Kosovo, we have
      estimated effective doses to resident populations using a well-established food
      web mathematical model (RESRAD code). The UNEP mission did not find any evidence
      of widespread contamination in Kosovo. Rather than the actual measurements, we
      elected to use a desk assessment scenario (Reference Case) proposed by the UNEP
      group as the source term for computer simulations. Specific applications to two
      Kosovo sites (Planeja village and Vranovac hill) are described. Results of the
      simulations suggest that radiation doses from water-independent pathways are
      negligible (annual doses below 30 microSv). A small radiological risk is expected
      from contamination of the groundwater in conditions of effective leaching and low
      distribution coefficient of uranium metal. Under the assumptions of the Reference
      Case, significant radiological doses (>1 mSv/year) might be achieved after many
      years from the conflict through water-dependent pathways. Even in this worst-case
      scenario, DU radiological risk would be far overshadowed by its chemical
      toxicity.

PMID- 12500809
TI  - Genomic instability in human osteoblast cells after exposure to depleted uranium:
      delayed lethality and micronuclei formation.
AB  - It is known that radiation can induce a transmissible persistent destabilization
      of the genome. We have established an in vitro cellular model using HOS cells to
      investigate whether genomic instability plays a role in depleted uranium (DU)
      induced effects. Transmissible genomic instability, manifested in the progeny of
      cells exposed to ionizing radiation, has been characterized by de novo
      chromosomal aberrations, gene mutations, and an enhanced death rate. Cell
      lethality and micronuclei formation were measured at various times after exposure
      to DU, Ni, or gamma radiation. Following a prompt, concentration-dependent acute
      response for both endpoints, there was de novo genomic instability in progeny
      cells. Delayed reproductive death was observed for many generations (36 days, 30
      population doublings) following exposure to DU, Ni, or gamma radiation. While DU
      stimulated delayed production of micronuclei up to 36 days after exposure, levels
      in cells exposed to gamma-radiation or Ni returned to normal after 12 days. There
      was also a persistent increase in micronuclei in all clones isolated from cells
      that had been exposed to nontoxic concentrations of DU. While clones isolated
      from gamma-irradiated cells (at doses equitoxic to metal exposure) generally
      demonstrated an increase in micronuclei, most clonal progeny of Ni-exposed cells
      did not. These studies demonstrate that DU exposure in vitro results in genomic
      instability manifested as delayed reproductive death and micronuclei formation.

PMID- 12500810
TI  - Forgetting all else: on the antecedents and consequences of goal shielding.
AB  - Six studies explore the role of goal shielding in self-regulation by examining
      how the activation of focal goals to which the individual is committed inhibits
      the accessibility of alternative goals. Consistent evidence was found for such
      goal shielding, and a number of its moderators were identified: Individuals'
      level of commitment to the focal goal, their degree of anxiety and depression,
      their need for cognitive closure, and differences in their goal-related tenacity.
      Moreover, inhibition of alternative goals was found to be more pronounced when
      they serve the same overarching purpose as the focal goal, but lessened when the
      alternative goals facilitate focal goal attainment. Finally, goal shielding was
      shown to have beneficial consequences for goal pursuit and attainment.

PMID- 12500811
TI  - Habits in everyday life: thought, emotion, and action.
AB  - To illustrate the differing thoughts and emotions involved in guiding habitual
      and nonhabitual behavior, 2 diary studies were conducted in which participants
      provided hourly reports of their ongoing experiences. When participants were
      engaged in habitual behavior, defined as behavior that had been performed almost
      daily in stable contexts, they were likely to think about issues unrelated to
      their behavior, presumably because they did not have to consciously guide their
      actions. When engaged in nonhabitual behavior, or actions performed less often or
      in shifting contexts, participants' thoughts tended to correspond to their
      behavior, suggesting that thought was necessary to guide action. Furthermore, the
      self-regulatory benefits of habits were apparent in the lesser feelings of stress
      associated with habitual than nonhabitual behavior.

PMID- 12500812
TI  - What doesn't kill me makes me stronger: the effects of resisting persuasion on
      attitude certainty.
AB  - The present research proposes a metacognitive framework for understanding
      resistance to persuasion. It is suggested that when people resist persuasion,
      they can become more certain of their initial attitudes. Several experiments
      demonstrated that when participants resisted persuasion, attitude certainty
      increased, but only when the attack was believed to be strong. For attacks
      believed to be weak, certainty was unchanged. It was also demonstrated that
      attitude certainty only increased when people actually perceived that persuasion
      had been resisted. This increased certainty was shown to have implications for
      resistance to subsequent attacks and the correspondence between attitudes and
      behavioral intentions. These findings suggest that when people perceive their own
      resistance, they form inferences about their attitudes that adjust for
      situational factors.

PMID- 12500813
TI  - The police officer's dilemma: using ethnicity to disambiguate potentially
      threatening individuals.
AB  - Using a simple videogame, the effect of ethnicity on shoot/don't shoot decisions
      was examined. African American or White targets, holding guns or other objects,
      appeared in complex backgrounds. Participants were told to "shoot" armed targets
      and to "not shoot" unarmed targets. In Study 1, White participants made the
      correct decision to shoot an armed target more quickly if the target was African
      American than if he was White, but decided to "not shoot" an unarmed target more
      quickly if he was White. Study 2 used a shorter time window, forcing this effect
      into error rates. Study 3 replicated Study 1's effects and showed that the
      magnitude of bias varied with perceptions of the cultural stereotype and with
      levels of contact, but not with personal racial prejudice. Study 4 revealed
      equivalent levels of bias among both African American and White participants in a
      community sample. Implications and potential underlying mechanisms are discussed.

PMID- 12500814
TI  - Three of my goals as editor.

PMID- 12500815
TI  - Altering intergroup perceptions by altering prevailing mode of cognitive
      representation: "they look like people".
AB  - This article reports the results of 3 studies that attempted to alter the mode of
      cognitive representation by training with nonsocial targets and then examined
      subsequent intergroup perception. In each study, participants examined an array
      of drinking glasses while receiving training in exemplar or prototype cognitive
      representation. Participants then responded to written trait descriptions of
      people (Experiment 1), photographs of the faces of members of European ethnic
      groups (Experiment 2), and full-body photographs of indigenous people (Experiment
      3). Compared with prototype training, exemplar training with the nonsocial
      targets resulted in more complex cognitive representations of the social targets
      and written descriptions of the social targets that were more individuated.
      Discussion considers the implications of these results for the study of
      intergroup perception.

PMID- 12500816
TI  - So close, and yet so far: does collectivism foster transparency overestimation?
AB  - The present research demonstrated that horizontal collectivism (HC), the tendency
      to emphasize social bonds and interdependence, is associated with overestimating
      the extent to which one's preferences, feelings, and behavioral inclinations are
      transparent to close others. The link between HC and felt transparency was
      mediated by self-other merging but was not significantly mediated by perceived
      similarity, behavioral closeness, or metaperception positivity. Evidence of a
      causal connection was obtained in an experiment where individuals for whom
      interdependence was primed exhibited greater transparency overestimation than did
      those for whom it was not. Additional results indicated that higher HC is
      associated with greater confidence but not greater accuracy in judgments about a
      friend. The authors argue that other perspective-taking deficits involving
      overuse of the self in judgments of others should also be exacerbated by the self
      other merging that is associated with HC.

PMID- 12500817
TI  - Procedural justice and status: status salience as antecedent of procedural
      fairness effects.
AB  - The current article explores status as an antecedent of procedural fairness
      effects (the findings that perceived procedural fairness affects people's
      reactions, e.g., their relational judgments). On the basis of the literature, the
      authors proposed that salience of the general concept of status leads people to
      be more attentive to procedural fairness information and that, as a consequence,
      stronger procedural fairness effects should be found. In correspondence with this
      hypothesis, Experiment 1 showed stronger procedural fairness effects on people's
      relational treatment evaluations in a status salient condition compared with a
      control condition. Experiment 2 replicated this effect and, in further
      correspondence with the hypothesis, showed that status salience led to increased
      cognitive accessibility of fairness concerns. Implications for the psychology of
      procedural justice are discussed.

PMID- 12500818
TI  - The experience of power: examining the effects of power on approach and
      inhibition tendencies.
AB  - Two studies of task-focused dyads tested the approach/inhibition theory of power
      (D. Keltner, D. H. Gruenfeld, & C. Anderson, in press), which posits that having
      power increases the tendency to approach and decreases the tendency to inhibit.
      Results provided preliminary support for the theory: Participants higher in
      personality dominance or assigned control over resources expressed their true
      attitudes, experienced more positive and less negative emotion, were more likely
      to perceive rewards (i.e., that their partner liked them), and were less likely
      to perceive threats (e.g., that their partner felt anger toward them). Most of
      these effects were mediated by the sense of power, suggesting that subjective
      feelings of power are an important component in the effects of power.

PMID- 12500819
TI  - Culture, identity consistency, and subjective well-being.
AB  - All individuals have multiple views of themselves. Whereas the consistency among
      the different aspects of identity is emphasized in Western cultures, the
      "multiple selves" are often viewed as coexisting realities in East Asian
      cultures. This research revisits the classic thesis in psychology that identity
      consistency is a prerequisite condition of psychological well-being. Between
      individuals (Study 1), people with a more consistent self-view had a more clear
      self-knowledge, were more assertive, and, most notably, had self-experiences that
      were less affected by the perspectives of others. Compared with North American
      participants (Study 2), Koreans viewed themselves more flexibly across
      situations, and their subjective well-being was less predictable from levels of
      identity consistency. Also, consistent individuals received positive social
      evaluations from others in the United States but not in Korea.

PMID- 12500820
TI  - Rebellious teens? Genetic and environmental influences on the social attitudes of
      adolescents.
AB  - Genetic and environmental influences in social attitudes were investigated in
      adopted and nonadopted children (N = 654) and their biological and adoptive
      relatives in the Colorado Adoption Project. Conservatism and religious attitudes
      were measured in the children annually from ages 12 to 15 and in the parents
      during the 12-year-old visit. Multivariate genetic model fitting indicated that
      both conservatism and religious attitudes are strongly influenced by shared
      family environmental factors throughout adolescence. In contrast to previous
      findings from twin studies, which suggest that genetic influence on social
      attitudes does not emerge until adulthood, the present study detected significant
      genetic influence in conservatism as early as age 12. There was no evidence of
      genetic influence, however, on religious attitudes during adolescence.

PMID- 12500821
TI  - An intraindividual process approach to the relationship between extraversion and
      positive affect: is acting extraverted as "good" as being extraverted?
AB  - This article investigates whether rapid variation within a person in extraversion
      is associated with positive affect variation in that person. In Study 1,
      participants reported their extraversion and positive affect every 3 hr for 2
      weeks. Each participant was happier when acting extraverted than when acting
      introverted. Study 2's diary methodology replicated the relationship for weekly
      variations in positive affect. Study 3's experimental methodology replicated the
      relationship when extraversion was manipulated within a fixed situation. Thus,
      the relationship between extraversion and positive affect, previously
      demonstrated between persons, also characterizes the internal, ongoing
      psychological functioning of individuals and is likely to be explained by
      something capable of rapid intraindividual variation. Furthermore, traits and
      states are at least somewhat isomorphic, and acting extraverted may increase well
      being.

PMID- 12500822
TI  - The self-importance of moral identity.
AB  - Recent theorizing in moral psychology extends rationalist models by calling
      attention to social and cultural influences (J. Haidt, 2001). Six studies using
      adolescents, university students, and adults measured the associations among the
      self-importance of moral identity, moral cognitions, and behavior. The
      psychometric properties of the measure were assessed through an examination of
      the underlying factor structure (Study 1) and convergent, nomological, and
      discriminant validity analyses (Studies 2 and 3). The predictive validity of the
      instrument was assessed by examinations of the relationships among the self
      importance of moral identity, various psychological outcomes, and behavior
      (Studies 4, 5, and 6). The results are discussed in terms of models of moral
      behavior, social identity measurement, and the need to consider moral self
      conceptions in explaining moral conduct.

PMID- 12500823
TI  - Predictive validity of an Implicit Association Test for assessing anxiety.
AB  - The Implicit Association Test (IAT) was adapted to measure anxiety by assessing
      associations of self (vs. other) with anxiety-related (vs. calmness-related)
      words. Study 1 showed that the IAT-Anxiety exhibited good internal consistency
      and adequate stability. Study 2 revealed that the IAT-Anxiety was unaffected by a
      faking instruction. Study 3 examined the predictive validity of implicit and
      explicit measures and showed that the IAT-Anxiety was related to changes in
      experimenter-rated anxiety and performance decrements after failure. Study 4
      found that several behavioral indicators of anxiety during a stressful speech
      were predicted by the IAT. Taken together, these studies show that the IAT
      Anxiety is a reliable measure that is able to predict criterion variables above
      questionnaire measures of anxiety and social desirability.

PMID- 12500824
TI  - Personality trait development from age 12 to age 18: longitudinal, cross
      sectional, and cross-cultural analyses.
AB  - Three studies were conducted to assess mean level changes in personality traits
      during adolescence. Versions of the Revised NEO Personality Inventory (P. T.
      Costa, Jr., & R. R. McCrae, 1992a) were used to assess the 5 major personality
      factors. A 4-year longitudinal study of intellectually gifted students (N = 230)
      was supplemented by cross-sectional studies of nonselected American (N = 1,959)
      and Flemish (N = 789) adolescents. Personality factors were reasonably invariant
      across ages, although rank-order stability of individual differences was low.
      Neuroticism appeared to increase in girls, and Openness to Experience increased
      in both boys and girls; mean levels of Extraversion, Agreeableness, and
      Conscientiousness were stable. Results extend knowledge of the developmental
      curve of personality traits backward from adulthood and help bridge the gap with
      child temperament studies.

PMID- 12500825
TI  - On the temporal stability of personality: evidence for differential stability and
      the role of life experiences.
AB  - The authors investigated the stability of personality and trait affect in young
      adults. In Studies 1 and 2, young adults were retested on a Big Five personality
      measure and a trait affect inventory over a 2.5-year and a 2-month period,
      respectively. Results from Study 1 point to positive mean-level changes;
      participants scored higher on Extraversion, Openness, Agreeableness, and
      Conscientiousness at Time 2. Affectively, participants experienced less negative
      affect and more positive affect at Time 2. Results from both retests provide
      clear evidence of differential stability. Affective traits were consistently less
      stable than the Big Five. Other analyses suggest that life events influence the
      stability of affective traits more than the Big Five.

PMID- 12500826
TI  - Minimally invasive esophagectomy in the elderly.
AB  - OBJECTIVES: In recent years, older patients are being referred for esophagectomy,
      and the associated morbidity and mortality is not well defined. Advances in
      minimally invasive techniques now allow minimally invasive esophagectomy (MIE) to
      be performed that may minimize the morbidity of this procedure. The objective of
      this report was to summarize our experience with MIE in the elderly. METHODS:
      From February 1997 through February 2001, 41 patients (14 women, 27 men) 75 years
      of age or older (mean age 78, range 75 to 89) underwent esophagectomy (28 for
      adenocarcinoma, 7 squamous, 6 Barrett's with high-grade dysplasia). RESULTS:
      Esophagectomy was performed in a minimally invasive fashion in 41 patients. No
      open conversions were necessary. The median ICU stay was 1 day (range 1 to 34).
      The median hospital stay was 7 days (range 5 to 50). Major morbidity occurred in
      19% of the cases and included 1 persistent air leak, 1 case of pneumonia with
      acute respiratory failure, 1 tracheal tear, 1 chylothorax, and 1 myocardial
      infarction. Three anastomotic leaks and 1 small bowel perforation occurred. All
      were recognized early and treated surgically. No perioperative mortalities took
      place. CONCLUSION: In our center, MIE was performed in elderly patients with an
      acceptable morbidity, low mortality, and reduced length of hospital stay compared
      with that in previous reports.

PMID- 12500827
TI  - Long-term results in the treatment of menorrhagia and hypermenorrhea with a
      thermal balloon endometrial ablation technique.
AB  - BACKGROUND AND OBJECTIVES: Evaluation of long-term results using a thermal
      balloon endometrial ablation technique to treat menorrhagia and hypermenorrhea,
      considered dysfunctional uterine bleedings. METHODS: A single-arm, prospective
      study with long-term follow-up of 48 months at the department of obstetrics and
      gynecology, University of Kiel, Germany. Following hysteroscopic evaluation of
      the uterine cavity and fractionated curettage, the Cavaterm endometrial thermal
      ablation technique was performed on 70 patients over the age of 40 with
      menorrhagia and hypermenorrhea in whom medical treatment had previously failed.
      The study included a group of 10 patients with adenomyosis and uterine fibroids.
      RESULTS: In 65 patients, a complete 48-month follow-up evaluation was possible:
      58% of patients reported amenorrhea and 33% hypomenorrhea. Nine percent of
      patients remained eumenorrheic. Fifty percent of the small group with failed
      indications for the procedure had to undergo a hysterectomy. CONCLUSIONS: The
      Cavaterm thermal coagulation system in the earlier mode of application (15
      minutes at a temperature of 70 degrees C and a pressure of 200 mm Hg) is a safe
      and highly effective method of endometrial ablation resulting in a minimal amount
      of posttreatment menstrual bleeding.

PMID- 12500828
TI  - The evil twins of chronic pelvic pain syndrome: endometriosis and interstitial
      cystitis.
AB  - OBJECTIVE: To determine the value in the initial laparoscopic and cystoscopic
      evaluation of avoiding the unnecessary delay in diagnosing the "evil twins" of
      chronic pelvic pain syndrome, endometriosis and interstitial cystitis. METHODS:
      We performed a retrospective review of 60 women ranging in age from 19 to 62.
      They underwent concurrent laparoscopy, cystoscopy, and hydrodistentions from
      January 1999 to October 2000. A gynecology and urology team performed these
      procedures in these 60 patients at a regional pelvic pain center in Northwest
      Ohio. RESULTS: Fifty-eight patients (96.6%) were diagnosed with interstitial
      cystitis by the presence of glomerulation and terminal hematuria according to
      National Institutes of Health criteria. A diagnosis of (active and inactive)
      endometriosis was found in 56 patients (93.3%). Biopsy-confirmed active
      endometriosis was found in 48 patients (80%). In the interstitial cystitis
      patient group (58), 54 patients had a diagnosis of (active and inactive)
      endometriosis (93.1%), and 47 patients had biopsy-confirmed active endometriosis
      (81%). In the group of 56 patients with a diagnosis of (active and inactive)
      endometriosis, 54 patients were found to have interstitial cystitis (96.4%). In
      the group of 48 patients with active biopsy-confirmed endometriosis, 47 have
      interstitial cystitis (97.7%). CONCLUSION: Patients with chronic pelvic pain
      syndrome are very difficult to manage. Eighty percent were found to have
      endometriosis and had numerous previous operations. Many patients failed to
      respond to multiple therapies. In many cases, pain persists even after a
      hysterectomy. Through our study, we showed the high prevalence and association of
      interstitial cystitis and endometriosis, the evil twins of chronic pelvic pain
      syndrome. It is absolutely necessary to perform both laparoscopic and cystoscopic
      examinations concurrently with the patient anesthetized in the initial evaluation
      and treatment of chronic pelvic pain syndrome to avoid unnecessary delay in
      making the diagnosis of the evil twins, because chronic pelvic pain syndrome can
      be caused by either or both of these entities. It is very important to have the
      gynecologists and urologists working as a team in making an early diagnosis to
      resolve these chronic debilitating diseases.

PMID- 12500829
TI  - Laparoscopic incisional and ventral hernia repair (LIVH): an evolving outpatient
      technique.
AB  - BACKGROUND AND OBJECTIVES: The contemporary results of open incisional and
      ventral hernia repair are unsatisfactory because of high recurrence rates and
      morbidity levels. Laparoscopic repair of ventral and incisional hernias (LIVH)
      can be accomplished in a simple, reproducible manner while dramatically lowering
      recurrence rates and morbidity. METHODS: One hundred consecutive patents
      underwent laparoscopic repair of their ventral and incisional hernias over a 27
      month period. Composix mesh and Composix E/X mesh (Davol Inc., Cranston, RI) were
      utilized for the repairs. Transfixion sutures were not used. RESULTS: All repairs
      were completed laparoscopically. No conversions to open techniques were
      necessary. No postoperative infections have been observed. One recurrent hernia
      was identified and subsequently repaired with the same technique. CONCLUSIONS:
      LIVH can be accomplished with a dramatic reduction in recurrence rates and
      morbidity. The technique for this repair is still in a state of evolution. The
      construction and handling characteristics of this particular type of mesh have
      allowed us to eliminate transfixion sutures and to simplify the repair technique
      while maintaining a very low recurrence rate.

PMID- 12500830
TI  - An effective omentoplasty technique in laparoscopic surgery for hydatid disease
      of the liver.
AB  - OBJECTIVES: The objectives of this study were to investigate the characteristics
      and outcome of patients with hydatid disease of the liver who were
      laparoscopically managed at our clinic and to define technical details including
      an effective method of omentoplasty with helical fasteners. METHODS: Between
      January 1998 and November 2000, 13 patients, mean age 36 years (range 23 to 63
      years), with hydatid disease of the liver were considered for laparoscopic
      surgery in our department. All the patients underwent laparoscopic surgical
      interventions. RESULTS: In all patients, laparoscopic cystotomy, unroofing, and
      omentoplasty with helical fasteners, which were originally designed for
      endoscopic hernia repair procedures, were performed. No conversion to laparotomy
      was necessary. In 1 case, with a single cyst in the right lobe, bile leakage was
      observed. No radiological recurrence was observed in an average follow-up of 17
      months (range 4 to 36 months). CONCLUSIONS: Obliteration of the residual cystic
      cavity decreases postoperative complication rates, so an effective omentoplasty
      is essential especially for laparoscopic procedures. Laparoscopy is quite
      feasible to perform in hydatid disease of the liver, and the use of helical
      fasteners allows effective omental flap fixation.

PMID- 12500831
TI  - Laparoscopic treatment of hepatic hydatid cysts with a liposuction device.
AB  - OBJECTIVE: We describe herein a surgical technique, whereby we use a liposuction
      device for the laparoscopic treatment of hepatic hydatid cysts (HHC). METHODS:
      Ten patients with 12 hepatic hydatid cysts were treated with this technique. All
      patients received pre- and postoperative antiscolecidal medications. The
      laparoscopic technique consisted of partial aspiration of the cyst fluid and
      replacement of the aspirated fluid with 10% Betadine. The Betadine solution was
      left in situ for 10 minutes. Evacuation of the cyst contents was carried out with
      the liposuction device. The residual cavity was unroofed by partial excision of
      the ectocyst. A drain was left alongside the cyst. No intra- or postoperative
      complications were encountered. RESULTS: All patients were mobilized freely, were
      allowed to eat a regular meal 6 hours after recovery from anesthesia, and were
      discharged on the third postoperative day. All patients resumed their normal
      household and work activities by the tenth postoperative day. The patients were
      regularly followed up every 2 months for 2 years. At follow-up in the surgical
      clinic, no evidence of recurrence was noted either clinically, serologically, or
      by imaging techniques. CONCLUSION: We conclude that the laparoscopic treatment of
      HHC is feasible and advantageous. We believe that the use of a liposuction device
      facilitates rapid and efficient evacuation of the viscid organic contents of the
      cyst and helps in the obliteration of the residual cavity.

PMID- 12500832
TI  - Palliative laparoscopic hepatico- and gastrojejunostomy for advanced pancreatic
      cancer.
AB  - Only 10% to 20% of pancreatic tumors are resectable at the time of diagnosis.
      Patients with advanced disease have a median survival of 4.9 months. Palliation
      is often required for biliary or duodenal obstruction, or both, and for pain.
      Optimal palliation should guarantee the shortest possible hospital stay and as
      long a survival as possible with a good quality of life. In recent years,
      treatment options for palliation of biliary and duodenal obstruction due to
      pancreatic cancer have broadened. Endoscopic and percutaneous biliary stenting
      have been shown to be successful tools for safe palliation of high-risk patients.
      Nevertheless, fit patients with unresectable pancreatic cancer benefit from
      surgery, which allows long-lasting biliary and gastric drainage. While
      laparoscopic cholecystojejunostomy and gastroenterostomy in patients with
      advanced pancreatic cancer have been widely reported, laparoscopic hepatico
      jejunostomy has been rarely described. In this article, we describe our technique
      of laparoscopic hepatico-jejunostomy and gastrojejunostomy. We also discuss
      current evidence on the indications for these procedures in patients with
      unresectable pancreatic cancer.

PMID- 12500833
TI  - Laparoscopic cholecystectomy and incidental carcinoma of the extrahepatic bilary
      tree.
AB  - BACKGROUND AND OBJECTIVES: Gallbladder carcinoma is found in 0.2% to 5% of
      patients undergoing cholecystectomy, and gallstones are found in 70% to 98% of
      patients with gallbladder carcinoma. Early diagnosis of carcinoma is difficult
      because of the absence of specific symptoms and the frequent association with
      chronic cholecystitis and gallstones. At present, laparoscopic cholecystectomy is
      the gold standard for the surgical treatment of symptomatic cholelithiasis and
      other benign gallbladder diseases. The aims of this study were to evaluate
      retrospectively the incidence of occasional and occult gallbladder carcinomas to
      ascertain the effect of laparoscopy on diagnosis and treatment of unexpected
      extrahepatic biliary tree carcinomas and to assess possible guidelines that can
      be taken into consideration when the problem is encountered. METHODS: Clinical
      records of 3900 patients undergoing laparoscopic cholecystectomy were reviewed.
      Patients with occasional (intraoperative = Group A) or occult (postoperative =
      Group B) diagnosis of gallbladder or common bile duct carcinoma entered the study
      group. Follow-up data were obtained in June 2000. RESULTS: A total of 14 patients
      (0.35%), 3 men and 11 women, mean age 60.8 years (range 37 to 73) with
      extrahepatic biliary tree carcinoma were found. Occasional carcinomas occurred in
      8 patients, occult carcinomas in 6. No deaths occurred in either group. The
      overall survival at mean follow-up of 30.5 months is 50%. Five patients are
      disease free, and 2 are alive with evidence of recurrence. DISCUSSION: In 2 large
      series of unselected consecutive laparoscopic cholecystectomy, only 14
      unsuspected malignant tumors of the extrahepatic biliary tree were found (0.35%).
      The limits of the preoperative workup and the difficult diagnosis of biliary
      tract carcinoma during laparoscopic cholecystectomy, has led to the present
      retrospective study and several significant recommendations.

PMID- 12500834
TI  - Laparoscopic coloanal anastomosis for low rectal cancer.
AB  - OBJECTIVES: Low anterior resection with hand-sutured coloanal anastomosis for low
      rectal cancer is technically feasible, and it does not compromise oncologic
      results. We describe herein the effectiveness of the operation in treating low
      rectal cancer by a laparoscopic approach followed by intraanal canal dissection.
      METHODS: From February 1999 to October 1999, we used a laparoscopic procedure to
      divide the inferior mesenteric vessels and to dissect downward into the pelvic
      cavity as low as possible. A purse-string suture 1-cm distal to the lower margin
      of the tumor was secured and transection of the rectum was performed
      circumferentially via the anal canal near the dentate line. The specimen was
      removed by the pull-through method and coloanal anastomosis was completed with
      hand suture. A protective loop ileostomy was fashioned. RESULTS: We operated on 8
      patients (4 males) with low tumor localization (average 4-cm above the dentate
      line). The age ranged from 45 to 83 years, with a median age of 64. The average
      operation time was 210 minutes (150 to 360 minutes), and the average blood loss
      was 250 cc (minimal to 750 cc). No operative mortalities occurred, but 2 patients
      had minor anastomotic slough complications. The average hospital stay was 13 days
      (7 to 26 days). The postoperative pathologic stage was T2N0M0 in 4 patients,
      T3N0M0 in 2 patients, T2N1M0 in 1 patient, and T3N2M0 in 1 patient. No local
      recurrence or distant metastasis occurred during the median 14 months (12 to 20
      months) of follow-up. CONCLUSION: Laparoscopic coloanal anastomosis combined with
      intraanal canal dissection is safe and technically feasible. The oncologic
      results seem not to be compromised, but need further evaluation.

PMID- 12500835
TI  - A new method to insert the DualMesh prosthesis for laparoscopic ventral
      herniorrhaphy.
AB  - The introduction of the prosthetic biomaterial during the laparoscopic repair of
      incisional and ventral hernias can present a challenge. Presented herein is a
      simplified method to fold and unfold the DualMesh (W. L. Gore and Associates,
      Flagstaff, AZ) prosthesis during this operation.

PMID- 12500836
TI  - ERCP's role in the management of acute biliary-pancreatic pathology in the
      laparoscopic era.
AB  - OBJECTIVES: Laparoscopic cholecystectomy (LC) combined with endoscopic retrograde
      cholangiopancreatography (ERCP) has been widely used in the management of the
      acute biliopancreatic pathology. Nevertheless, controversy remains about the
      appropriate timing for retrograde cholangiopancreatography. METHODS: A
      retrospective study was undertaken on a consecutive series of 117 patients with
      acute biliary-pancreatic pathology, who underwent laparoscopic cholecystectomy
      between April 1995 and April 1999. Criteria for preoperative endoscopic
      retrograde cholangiopancreatography were defined, and the patients were divided
      into 3 groups based on the presence or absence of a preoperative retrograde
      cholangiopancreatography indication: (1) ERCP+LC group: patients with retrograde
      cholangiopancreatography indicated and performed (n = 30); (2) LC group: patients
      without retrograde cholangiopancreatography criteria treated only by LC (n = 47);
      (3) LC-ERCP group: patients with retrograde cholangiopancreatography criteria but
      not performed (n = 40). RESULTS: The groups were similar in age, sex, ASA, and
      clinical diagnosis. No statistical differences occurred in operative times (73.8
      min, 68 min, 67 min), major complications (3.3%, 4.25%, 12.5%), and mean
      postoperative stay (3.7 +/- 4; 4.7 +/- 2; 5.7 +/- 2). Postoperative retrograde
      cholangiopancreatography had to be used, respectively, in 0%, 10.6%, and 7.5%.
      The best predictive criteria for common bile duct pathology were
      choledocholithiasis on an ultrasound scan and the presence of cholangitis. The
      other criteria tested had a low predictive value. CONCLUSIONS: Preoperative
      endoscopic retrograde cholangiopancreatography followed by early laparoscopic
      cholecystectomy can be performed safely in acute biliary-pancreatic pathology,
      avoiding 2-stage treatment of these patients and minimizing hospital stay and
      inconvenience to the patients. Nevertheless, this therapeutic/diagnostic tool
      must be used selectively.

PMID- 12500838
TI  - Outpatient laparoscopic cholecystectomy: a reality.
AB  - BACKGROUND: The author reports on his personal experience with outpatient
      laparoscopic cholecystectomy (LC), focusing on the main guidelines for
      preoperative and postoperative care and operating technique. METHODS: From
      January 1, 2000 to December 31, 2000, 71 laparoscopic cholecystectomies were
      performed on outpatients. The patients remained in the outpatient surgery center
      for 36 hours. In 4 cases, the operation was converted into laparotomy. Twenty
      patients remained in the hospital and were discharged 5 to 7 days later. Twelve
      were rehospitalized due to pathologies that could not be treated at home.
      RESULTS: In all 71 cases, a complete remission of the symptoms occurred, and none
      of the patients died either during the operation or during the postoperative
      period. Eighty percent of patients were treated in outpatient surgery centers.
      CONCLUSIONS: With clear guidelines, LC is a major surgical operation that can be
      performed in outpatient surgery centers without death or other major
      complications and with very good remission of symptoms.

PMID- 12500837
TI  - The sixth decision regarding perforated duodenal ulcer.
AB  - This presentation reviews the literature regarding the current surgical treatment
      of perforated ulcers, describes the surgical techniques for laparoscopic repair,
      and reviews the clinical algorithm used by laparoscopic surgeons at Duke
      University Medical Center.

PMID- 12500839
TI  - Minilaparoscopic cystectomy and appendectomy in late second trimester.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic ovarian cystectomy and appendectomy
      during the early second trimester have been widely reported. However, the use of
      both procedures in advanced gestation is rare. We propose a minilaparoscopic
      approach for performing these 2 procedures in a woman 24-weeks pregnant. METHODS:
      We describe the case and laparoscopic management of acute abdominal pain at the
      24th week of pregnancy. Microlaparoscopy under ultrasound guidance was used for
      the first trocar insertion to prevent injury to the uterus. It was followed by
      minilaparoscopic ovarian cystectomy and appendectomy. RESULTS: Premature
      contractions occurred after the operation, but they were controlled with a single
      tocolytic agent, and an apparently healthy female baby was born uneventfully via
      Cesarean delivery at 41 weeks of gestation. CONCLUSION: Minilaparoscopic ovarian
      cystectomy and appendectomy can be carried out in the late second trimester
      without serious sequela.

PMID- 12500840
TI  - Laparoscopic removal of a symptomatic rudimentary uterine horn in a perimenarchal
      adolescent.
AB  - An adolescent patient with a symptomatic, noncommunicating, rudimentary uterine
      horn is described. Diagnosis was suggested by ultrasonography and treatment was
      by laparoscopic resection. A review of other pediatric cases as well as the adult
      literature gives evidence that laparoscopic resection is worth considering in
      such cases.

PMID- 12500841
TI  - Laparoscopic heminephrectomy for benign disease of the horseshoe kidney.
AB  - BACKGROUND AND OBJECTIVE: Minimally invasive surgery plays a definitive role in
      the management of complications associated with the horseshoe kidney (HK).
      Aberrant vessels, the renal isthmus, and renal ectopia are all unique features of
      this anomaly that make the laparoscopic approach a challenge. We report our
      experience with this technique in 2 patients. METHODS: Two patients with an HK
      were evaluated for recurrent urinary tract infection. In both cases, the
      nonfunctioning renal moiety was demonstrated by renal scan. A transperitoneal
      laparoscopic heminephrectomy was performed. The Endostapler device was used to
      divide the renal isthmus. RESULTS: The operative time was less than 3 hours.
      Blood loss was negligible. No intraoperative complications occurred. The hospital
      stay was 48 hours. Postoperative discomfort was minimal. CONCLUSION: Laparoscopic
      heminephrectomy is a safe and feasible approach for benign diseases of the HK.
      The Endostapler is a useful adjunct in the division of the renal isthmus.

PMID- 12500842
TI  - Laparoscopic repair of blunt traumatic anterior abdominal wall hernia.
AB  - Traumatic abdominal wall hernia is a relatively uncommon finding secondary to
      blunt trauma. We report a unique case of laparoscopic diagnosis and immediate
      repair of a traumatic anterior abdominal wall hernia after blunt abdominal
      trauma.

PMID- 12500843
TI  - Laparoscopic control of a leaking inferior mesenteric vessel secondary to trocar
      injury.
AB  - BACKGROUND: Vascular injury is the most urgent type of trauma at laparoscopy. It
      is thought that the rate of vascular injury may increase as the complexity of
      laparoscopic surgery increases. To our knowledge, this is the first report of
      laparoscopic management of a leaking inferior mesenteric artery caused by trauma.
      METHOD: Case report. RESULTS: Successful laparoscopic management of a leaking
      inferior mesenteric artery secondary to trocar insertion. CONCLUSION:
      Laparoscopic management of a vascular injury in a hemodynamically stable patient
      is possible.

PMID- 12500844
TI  - Role of intraoperative cholangiography in detecting rare bile duct anomalies.
AB  - A case of an anomalous extrahepatic biliary system is reported in which the right
      hepatic duct was found to enter the infundibulum of the gallbladder. In this
      case, a selective intraoperative cholangiography has prevented a possible major
      iatrogenic injury.

PMID- 12500845
TI  - Hiatal stenosis after laparoscopic Nissen fundoplication: a report of 2 cases.
AB  - Persistent postoperative dysphagia (PPD) is one of the most troublesome
      complications of laparoscopic antireflux surgery. Hiatal stenosis, although rare,
      is a serious complication and is one of the causes of PPD after antireflux
      procedures. In the 2 presented patients, progressive dysphagia started
      immediately after the antireflux procedure and did not respond to esophageal
      dilations. The cause of dysphagia in both patients was hiatal stenosis and was
      corrected laparoscopically.

PMID- 12500846
TI  - The ultrasonic trocar provides an easy, sharp, bloodless, and repeatable approach
      to the abdominal cavity.
AB  - Reusable trocars have the advantage of being more cost-effective than disposable
      trocars. However, the reusable trocar does lose its sharpness on insertion with
      repetitive insertion. Nonreusable trocars are expensive, but the sharpness of the
      knife facilitates insertion. Nonreusable trocars have a safety shield system
      designed to decrease abdominal organ injury, though the potential problem of
      bleeding from the abdominal wall port site has yet to be resolved. We therefore
      developed a novel ultrasonic vibrating trocar that does not lose its sharpness
      even with repetitive insertion. This trocar prevents bleeding by means of an
      ultrasonic cavitation effect. The ultrasonic vibrating trocar has the advantage
      of ease of insertion, and the force required for new reusable trocar insertion
      was only 34% of the force required for insertion of commercially available
      nonreusable trocars. The force required for multiply used conventional reusable
      ultrasonic vibrating trocar insertion, ie, 900 insertions, was maintained at less
      than 46% of the force required by the corresponding nonreusable trocars. Bleeding
      from the abdominal wall was prevented by an ultrasonic cavitation effect.

PMID- 12500847
TI  - Multimodality paradigms for a healthy multimodality society.
AB  - The American Radium Society encourages the study of cancer in all its aspects,
      encourages liaison among the various medical specialists and allied scientists,
      and thereby champions multimodality oncologic care. Past and present membership
      rolls of the Society read like a "Who's Who" of cancer care and include
      distinguished physicians and allied scientists whose primary focus spans the
      spectrum of oncologic subspecialties; however, the current distribution of areas
      of expertise may not necessarily be optimal. Moreover, the practice of medicine
      constantly is changing, and we, as a society, should be prepared to evolve with
      it. For example, treatment of cancers arising in the head and neck region has
      changed dramatically during the past decade. The successful integration of
      concurrent chemotherapy with radiation therapy has created new paradigms for
      optimal care. These paradigms potentially decrease the risk of distant
      metastases, improve the local-regional control of disease, increase the
      likelihood of organ preservation, and reduce the risk posed by microscopic-sized
      unresected disease. Yet, much remains unknown, some of the available data appear
      contradictory, and much is left to do. Similar analysis persuasively argues that
      other groups that have specific expertise must also play a vital role in modern
      oncologic care, including radiation biologists, medical physicists, and molecular
      biologists. Yet, the current environment creates formidable obstacles to
      participation in the American Radium Society's mission. We must improve our
      understanding of these barriers and implement original solutions to ensure that
      our society remains in the forefront of progress in the fight against cancer. In
      particular, programs to increase the educational reach of the ARS need to be
      devised, implemented, and nurtured. The ARS has a long, proud history, but we
      should not seek to live in its past. We must seek continuously and welcome
      enthusiastically changes in the Society that will align the ARS with paradigms of
      cutting-edge oncologic care.

PMID- 12500848
TI  - Hodgkin's disease: a model for interdisciplinary cancer management: 2002 Janeway
      lecture.

PMID- 12500849
TI  - The conundrum of prostate cancer.

PMID- 12500850
TI  - The sentinel node biopsy and colon cancer revisited.

PMID- 12500851
TI  - Correlating dose and volume of irradiated lung with pulmonary function tests.

PMID- 12500852
TI  - Stage T1c prostate cancer: a heterogeneous category with widely varying
      prognosis.
AB  - PURPOSE: Stage T1c prostate cancer is defined as nonpalpable disease diagnosed by
      needle biopsy. As more patients are being diagnosed early because of prostate
      specific antigen (PSA) screening, the distribution of patients by stage has
      shifted dramatically. Although this group has traditionally been characterized as
      having early-stage disease and the best prognosis, on review of these patients,
      we instead found a very heterogeneous group with a wide spectrum of outcomes that
      depend on both patient (Gleason grade and pretreatment PSA) and treatment (dose)
      factors. METHODS AND MATERIALS: A retrospective analysis was performed on 353
      patients with stage T1c prostate adenocarcinoma who were referred for radiation
      therapy from 1989-1999. All patients underwent central review of pathology.
      Patients were treated with external-beam radiation to doses of 60-78 Gy; 66% of
      the patients were treated with a dose of 70 Gy or higher. Clinical local
      recurrence, nodal recurrence, distant metastases, and PSA relapse were recorded.
      Kaplan-Meier methodology was used to determine survival. For evaluation of
      prognostic variables, the patients were grouped by Gleason score (2-6, 7, 8-10),
      pretreatment PSA level (< 10, 10-20, > 20 ng/mL), and dose delivered to the
      prostate (< or = 70 Gy, > 70 Gy). The log-rank test was used for univariate
      analysis, and Cox-regression was used for multivariate analysis. RESULTS: The
      median age was 69 years, and the median follow-up of surviving patients was 47
      months. As a percentage of all patients with prostate cancer, stage T1c
      continually increased from 6% in 1989 to 47% in 1999. Of the 353 patients with
      T1c, 66% of the patients were in the Gleason group of 2-6, 27% had a Gleason
      score of 7, and 7% had a Gleason score of 8-10. Sixty-five percent of the group
      had a pretreatment PSA level of < 10 ng/ mL, 31% had a PSA level of 10-20 ng/mL,
      and 5% had a PSA level of > 20 ng/mL. For the entire group, the 8-year overall
      survival was 86%, and PSA relapse-free survival was 78%. By univariate analysis,
      Gleason score and pretreatment PSA were significant predictors of overall
      survival and PSA relapse-free survival. For PSA relapse-free survival, a
      radiation dose of more than 70 Gy was also a significant factor. By multivariate
      analysis, Gleason score, pretreatment PSA level, and radiation dose over 70 Gy
      were significant predictors of PSA relapse-free survival. As expected, patients
      with Gleason score < or = 6 and pretreatment PSA < 10 had an 8-year RFS of 90%,
      whereas patients with Gleason score of 8-9 and pretreatment PSA > 20 had a
      relapse-free survival of zero percent. DISCUSSION: Contrary to general
      assumption, stage T1c prostate cancer is composed of a very heterogeneous group
      of patients with varying outcomes. When treatment modalities and institutional
      data are evaluated, the spectrum of disease must be accounted for by additional
      prognostic factors and subset analysis. Improvement in prostate imaging and
      multiple core biopsies may be helpful in better defining the extent of disease in
      the individual patient.

PMID- 12500853
TI  - Does tumor burden limit the accuracy of lymphatic mapping and sentinel lymph node
      biopsy in colorectal cancer?
AB  - PURPOSE: Sentinel lymph node (SLN) biopsy is a widely accepted method for staging
      breast cancer and melanoma, and it has recently been proposed as a means of
      improving staging in colorectal cancer. However, lymphatic mapping in colorectal
      cancer has been plagued by studies demonstrating high false-negative rates. The
      purpose of this study was to evaluate possible mechanisms for high false-negative
      rates after SLN biopsy in colorectal cancer. We hypothesized that poor accuracy
      may be due to bulky tumor or complete replacement of lymph nodes by tumor.
      PATIENTS AND METHODS: Patients with colorectal adenocarcinoma underwent standard
      colorectal resection with lymphatic mapping. At operation, 1 mL of isosulfan blue
      dye was injected at the tumor site, using either an in vivo or an ex vivo
      technique. Routine pathological evaluation was performed. The sentinel node was
      examined by hematoxylin and eosin stains, and if these results were negative, by
      cytokeratin immunohistochemistry. The patient's age, operation type, tumor stage,
      tumor diameter, method of SLN detection, presence of palpable nodes, and
      pathological description of nodes completely replaced by tumor were recorded.
      RESULTS: Fifty patients (mean age, 62.8, 50% men) undergoing colorectal cancer
      resection underwent 51 lymphatic mapping procedures. Right- and left-sided
      colorectal resections were almost equally distributed (48% vs 42%). SLNs were
      successfully identified in 47 of 51 specimens (92%). The mean number of SLNs
      obtained from each specimen was 1.5 (range, 1-5). Routine pathological evaluation
      demonstrated lymph node metastasis in 20 of the 47 patients (43%) who had an SLN
      identified. The SLN was positive for metastasis in 10 of these 20 patients (50%).
      Ten of 20 patients with metastatic disease had a negative SLN, resulting in a
      false-negative rate of 50%. The false-negative rate was significantly higher in
      patients undergoing left-sided procedures versus right-sided procedures.
      Differences among gender, tumor stage, tumor diameter, method of SLN detection,
      presence of palpable nodes, and pathological description of nodes completely
      replaced by tumor were not associated with a higher false-negative rate.
      DISCUSSION: Identification of the SLN in colorectal cancer is technically
      possible in more than 90% of patients. However, SLN status correlates poorly with
      the true nodal status of the colorectal cancer, and the false-negative rate is
      50%. This high false-negative rate is not clearly explained by extensive tumor
      burden, and it was also independent of gender, tumor stage, and type of lymphatic
      mapping technique. However, staging accuracy was lower in patients who underwent
      left-sided colorectal resection. Further studies are needed to clarify the
      limitations of lymphatic mapping in colorectal cancer.

PMID- 12500854
TI  - Effect of concurrent radiation therapy and chemotherapy on pulmonary function in
      patients with esophageal cancer: dose-volume histogram analysis.
AB  - PURPOSE: The pulmonary effects of concurrent radiation therapy and chemotherapy
      were studied in patients enrolled in a phase I trial for esophageal cancer.
      MATERIALS AND METHODS: Pulmonary function tests were performed prospectively
      before and after combined-modality therapy (oxaliplatin, 5-fluorouracil, and
      radiation therapy) in 20 patients with esophageal cancer. Cumulative and
      differential lung DVH analysis from 0 to 5400 cGy in 25-cGy intervals was
      performed for the last 15 patients. Correlation between radiation exposure in
      various dose ranges and percent reduction in pulmonary function tests was
      calculated as an exploratory analysis. RESULTS: Significant reductions in carbon
      monoxide diffusion capacity corrected for hemoglobin (12.3%) and total lung
      capacity (2.5%) were evident at a median of 15.5 days after radiation therapy.
      DVH analysis revealed that the single dose of maximum correlation between lung
      volume radiation exposure and lung function reduction was less than 1000 cGy for
      all pulmonary functions. The percent lung volume that received a total dose
      between 700 and 1000 cGy maximally correlated with the percent reductions in
      total lung capacity and vital capacity, and the absolute lung volume that
      received a total dose between 700 and 1000 cGy maximally correlated with the
      percent reductions in total lung capacity, vital capacity, and carbon monoxide
      diffusion capacity. DISCUSSION: Significant declines in carbon monoxide diffusion
      capacity and total lung capacity are evident immediately after the administration
      of conformal radiation therapy, oxaliplatin, and 5-fluorouracil for esophageal
      cancer. Other lung functions remain statistically unchanged. The percent or
      absolute lung volume that received a total dose between 700 and 1000 cGy may be
      significantly correlated with the percent decline of carbon monoxide diffusion
      capacity, total lung capacity, and vital capacity. These associations will be
      evaluated further in a follow-up study.

PMID- 12500855
TI  - Global gene expression changes during neoadjuvant chemotherapy for human breast
      cancer.
AB  - PURPOSE: The purpose of this study was to analyze global gene expression changes
      in serial tumor core biopsy specimens taken during neoadjuvant chemotherapy for
      primary breast cancer. PATIENTS AND METHODS: Core biopsy specimens from tumors
      were obtained before treatment and 24 and/or 48 hours after treatment from 21
      women who were beginning chemotherapy for breast cancer. RNA was extracted, and
      radiolabeled complementary DNA was synthesized. The complementary DNA probes were
      hybridized to high-density microarray membranes that contained more than 25,000
      human sequence clones. Hierarchical cluster analysis was used to compare the
      degree of similarity between expression profiles. RESULTS: Twenty-five (45%) of
      the 56 available core specimens yielded sufficient quantity and quality RNA for
      microarray analysis. Microarray profiles were performed only on samples from
      patients with pretreatment and posttreatment specimens, resulting in serial data
      sets for five patients (14 specimens). The serial samples from individual
      patients clustered more closely than the samples taken from different patients.
      Analyses of the variance of individual gene expression showed that there were
      significantly fewer genes with fivefold differences in expression in an
      individual tumor at different times (average, 359 genes) versus pretreatment
      samples of different tumors (average, 732 genes). Patients with a good
      pathological response to treatment had gene patterns that clustered distinctly
      from those of poor responders. Significant transcriptional response occurred in
      all patients during therapy. Surprisingly, all patients had different genes
      change after chemotherapy, with no single gene having a significant expression
      change in all five patients. DISCUSSION: This is the first report to show global
      gene expression changes during chemotherapy in a human solid tumor. Comprehensive
      gene expression profiles of more than 25,000 genes can be obtained from core
      biopsy specimens. A remarkable diversity in transcriptional response was observed
      for individual cases. Further data are needed to determine whether gene profiling
      can predict response to chemotherapy.

PMID- 12500856
TI  - Thallium-201 imaging in evaluation of Hodgkin's disease.
AB  - PURPOSE: The role of Ga 67 in the evaluation of Hodgkin's disease has been widely
      established. Tl 201 has been used to evaluate a wide variety of malignant
      lesions. This prospective study was performed to evaluate the role of Tl 201
      imaging in Hodgkin's disease at the time of initial presentation and in the
      assessment of response to therapy, relapse, and remission. METHODS: Fifty-one
      consecutive patients (23 female, 28 male) with known Hodgkin's disease underwent
      111 Tl 201 and Ga 67 studies. The age range was 16-56 years (mean age, 34.7
      years). The histopathologies included nodular sclerosis (in 31 cases), mixed
      cellularity (in 12), lymphocytic predominant (in five), lymphocytic depletion (in
      one), and unknown (in two). All patients underwent whole-body imaging after
      intravenous injection of 3 mCi of Tl 201 chloride and 10 mCi of Ga 67 citrate.
      Comparison with Ga 67 imaging, anatomical imaging (computed tomography and/or
      magnetic resonance imaging), and clinical correlation were performed. RESULTS:
      The combined analysis of all various histologies demonstrated that a comparison
      of Tl 201 with Ga 67 scintigraphy revealed a sensitivity of 0.76 versus 0.89; a
      specificity of 0.96 versus 0.73, an accuracy of 0.86 versus 0.81, a positive
      predictive value of 0.95 versus 0.77, and a negative predictive value of 0.81
      versus 0.87. Tl 201 imaging was similar in sensitivity, specificity, and accuracy
      among the nodular sclerosis and the mixed-cellularity Hodgkin's disease.
      CONCLUSION: Tl 201 imaging offers more specificity with a higher positive
      predictive value in the diagnosis of Hodgkin's disease. The Ga 67 study is more
      sensitive than Tl 201 in the detection of disease. There is no significant
      difference in accuracy and negative predictive value between the two studies.
      Therefore, we recommend Tl 201 imaging in the initial evaluation and assessment
      of patients' response to radiation therapy and/or chemotherapy.

PMID- 12500857
TI  - The use of rectal balloon during the delivery of intensity modulated radiotherapy
      (IMRT) for prostate cancer: more than just a prostate gland immobilization
      device?
AB  - PURPOSE: The purpose of this study was to investigate the role of a rectal
      balloon for prostate immobilization and rectal toxicity reduction in patients
      receiving dose-escalated intensity-modulated radiotherapy for prostate cancer.
      PATIENTS AND METHODS: Patients with localized prostate cancer who were undergoing
      intensity-modulated radiotherapy were treated in a prone position, immobilized
      with a customized Vac-Lok bag (MED-TEC, Orange City, IA). A rectal balloon with
      100 cc of air was used to immobilize the prostate. The prostate displacements
      were measured using computed tomography (CT)-CT fusion on 10 patients who
      received radioactive seed implant before intensity-modulated radiotherapy. They
      were scanned twice weekly during 5 weeks of intensity-modulated radiotherapy, and
      breathing studies were also performed. Rectal toxicity was evaluated by use of
      Radiation Therapy Oncology Group scoring in 100 patients. They were treated to a
      mean dose of 76 Gy over 35 fractions (2.17-Gy fraction size). Dose-volume
      histogram of the rectum was assessed. A film phantom was constructed to simulate
      the 4-cm diameter air cavity that was created by the rectal balloon. Kodak XV2
      films (Rochester NY) were used to measure and compare dose distribution with and
      without the air cavity. A fraction of 1.25 Gy was delivered to the phantom at
      isocenter with 15-MV photons by use of the NOMOS Peacock system and the MIMiC
      treatment delivery system (Sewickley, PA). RESULTS: The anterior-posterior and
      lateral prostate displacements were minimal, on the order of measurement
      uncertainty (approximately 1 mm). The standard deviation of superior-inferior
      displacement was 1.78 mm. Breathing studies showed no organ displacement during
      normal breathing when the rectal balloon was in place. The rectal toxicity
      profile was very favorable: 83% (83/100) patients had no rectal complaint, and
      11% and 6% had grade 1 and 2 toxicity, respectively. Dose-volume histogram
      analysis revealed that in all of the patients, no more than 25% of the rectum
      received 70 Gy or greater. As visualized by film dosimetry, the dose at air
      tissue interface was approximately 15% lower than that without an air cavity. The
      dose built up rapidly so that at 1 and 2 mm, the differential was approximately
      8% and 5%, respectively. The dosimetric coverage at the depth of the posterior
      prostate wall was essentially equal, with or without the air cavity. DISCUSSION:
      The use of a rectal balloon during intensity-modulated radiotherapy significantly
      reduces prostate motion. Prostate immobilization thus allows a safer and smaller
      planning target volume margin. It has also helped spare the anterior rectal wall
      (by its dosimetric effects) and reduced the rectal volume that received high-dose
      radiation (by rectal wall distension). All these factors may have further
      contributed to the decreased rectal toxicity achieved by intensity-modulated
      radiotherapy, despite dose escalation and higher-than-conventional fraction size.

PMID- 12500858
TI  - Clinical psychologists' theory-based representations of mental disorders predict
      their diagnostic reasoning and memory.
AB  - The theory-based model of categorization posits that concepts are represented as
      theories, not feature lists. Thus, it is interesting that the Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric
      Association, 1994) established atheoretical guidelines for mental disorder
      diagnosis. Five experiments investigated how clinicians handled an atheoretical
      nosology. Clinicians' causal theories of disorders and their responses on
      diagnostic and memory tasks were measured. Participants were more likely to
      diagnose a hypothetical patient with a disorder if that patient had causally
      central rather than causally peripheral symptoms according to their theory of the
      disorder. Their memory for causally central symptoms was also biased. Clinicians
      are cognitively driven to use theories despite decades of practice with the
      atheoretical DSM.

PMID- 12500859
TI  - Acquisition of categorical color perception: a perceptual learning approach to
      the linguistic relativity hypothesis.
AB  - Color perception can be categorical: Between-category discriminations are more
      accurate than equivalent within-category discriminations. The effects could be
      inherited, learned, or both. The authors provide evidence that supports the
      possibility of learned categorical perception (CP). Experiment 1 demonstrated
      that observers' color discrimination is flexible and improves through repeated
      practice. Experiment 2 demonstrated that category learning simulates effects of
      "natural" color categories on color discrimination. Experiment 3 investigated the
      time course of acquired CP. Experiment 4 found that CP effects are acquired
      through hue- and lightness-based category learning and obtained interesting data
      on the dimensional perception of color. The data are consistent with the
      possibility that language may shape color perception and suggest a plausible
      mechanism for the linguistic relativity hypothesis.

PMID- 12500860
TI  - Regularities of source recognition: ROC analysis.
AB  - Source memory has become the focus of a growing number of investigations in a
      variety of fields. An appropriate model for source memory is, therefore, of
      increasing importance. A simple 2-dimensional signal-detection model of source
      recognition is presented. The receiver operating characteristics (ROCs) obtained
      from 3 experiments are then used to test the model. The data demonstrate 3
      regularities: convex ROCs, z-ROCs with linear slopes of 1.00, and slightly
      concave z-ROCs. Two of these regularities support the model. The 3rd requires a
      revision of the model. This revised model is fitted to the data. The implications
      of these regularities for other theories are also discussed.

PMID- 12500861
TI  - Expectancy in melody: tests of children and adults.
AB  - Melodic expectancies among children and adults were examined. In Experiment 1,
      adults, 11-year-olds, and 8-year-olds rated how well individual test tones
      continued fragments of melodies. In Experiment 2, 11-, 8-, and 5-year-olds sang
      continuations to 2-tone stimuli. Response patterns were analyzed using 2 models
      of melodic expectancy. Despite having fewer predictor variables, the 2-factor
      model (E. G. Schellenberg, 1997) equaled or surpassed the implication-realization
      model (E. Narmour, 1990) in predictive accuracy. Listeners of all ages expected
      the next tone in a melody to be proximate in pitch to the tone heard most
      recently. Older listeners also expected reversals of pitch direction,
      specifically for tones that changed direction after a disruption of proximity and
      for tones that formed symmetric patterns.

PMID- 12500862
TI  - When standards are wide of the mark: nonselective superiority and inferiority
      biases in comparative judgments of objects and concepts.
AB  - People are frequently required to judge how particular group members measure up
      against others in their group. According to the local-comparisons-general
      standards (LOGE) approach, in these member-to-group comparisons, people fail to
      use the normatively appropriate local (group) standard and are infelicitously
      affected by a more general standard (involving instances from outside the judged
      group). Within positive groups, target group members are judged superior to the
      other members of the group, and within negative groups, inferior. To date, these
      nonselective superiority and inferiority biases have been demonstrated solely in
      judgments about human beings. In 6 experiments, nonselective biases were found in
      perceptual, affective, and cognitive judgments of nonhuman targets, objects, and
      concepts, thus supporting a cognitive rather than a social account.

PMID- 12500863
TI  - Constraints have different concurrent effects and aftereffects on variability.
AB  - Three experiments showed that constraints imposed early in learning have
      different effects on variability when they are in effect and after they are
      removed. Task constraints, which determine how something can be done, limited the
      number of possible responses in a computer game. Variability constraints, which
      specify how differently something must be done, required that each response
      differ from some number of prior responses. Less restrictive constraints
      (Experiments 1 and 2) produced higher variability during the constraints. More
      restrictive constraints (Experiments 2 and 3) led to higher variability after the
      constraints were relaxed. The authors discuss how these differences reflect
      strategies acquired during the constraints (default rules) and modified in
      closely related ways (exception rules) afterward.

PMID- 12500864
TI  - Individual differences in working memory within a nomological network of
      cognitive and perceptual speed abilities.
AB  - It has become fashionable to equate constructs of working memory (WM) and general
      intelligence (g). Few investigations have provided direct evidence that WM and g
      measures yield similar ordering of individuals. Correlational investigations have
      yielded mixed results. The authors assess the construct space for WM and g and
      demonstrate that WM shares substantial variance with perceptual speed (PS)
      constructs. Thirty-six ability tests representing verbal, numerical, spatial, and
      PS abilities; the Raven Advanced Progressive Matrices; and 7 WM tests were
      administered to 135 adults. A nomological representation for WM is provided
      through a series of cognitive and PS ability models. Construct overlap between PS
      and WM is further investigated with attention to complexity, processing
      differences, and practice effects.

PMID- 12500865
TI  - Comment on "Competition for consciousness among visual events: the psychophysics
      of reentrant visual processes" (Di Lollo, Enns, & Rensink, 2000).
AB  - V. Di Lolo, J. T. Enns, and R. A. Rensink (2000) reported properties of masking
      that they claimed were inconsistent with all current models. The current authors
      show, through computer simulation, that many current models can account for V. Di
      Lollo et al.'s (2000) data. Although V. Di Lollo et al. (2000) argued that their
      data could be accounted for only with models that incorporate reentrant
      processing, the current authors show that reentrant processing is not necessary.

PMID- 12500867
TI  - A progress report on the blade implant.

PMID- 12500868
TI  - A nonradiologic method for estimating bone volume for dental implant placement in
      the completely edentulous arch.
AB  - A method is described for estimating bone volume and contour for dental implant
      placement in the edentulous arch.

PMID- 12500869
TI  - Management of an implant case that required retreatment: a case report.
AB  - The presented case represents how the lack of a preoperative panoramic radiograph
      or any radiograph contributed to incorrect case planning, poor implant selection,
      and the careless surgical placement of an implant into or dangerously close to
      the lower left mental foramen, resulting in a paresthesia of 9 months duration.
      Two implants were surgically removed and the bone defects were grafted with a
      mixture of irradiated cancellous bone plus Biogran. One implant was sectioned and
      intentionally "put to sleep." The case was successfully completed with a lower
      bar overdenture supported by 4 screw implants placed in alternate sites, opposing
      a custom fabricated maxillary denture with a lingualized occlusal scheme.

PMID- 12500870
TI  - Immediate implants in fresh posterior extraction sockets: report of two cases.
AB  - This article demonstrates the use of an implant insertion method for the
      posterior region. Following an atraumatic extraction of a posterior tooth, an
      immediate implant can be placed at the time of the extraction. A surgical
      technique that involves the insertion of the implant into the interseptal bone of
      a multirooted posterior tooth extraction socket in a manner to provide initial
      stabilization of the implant and partial fill of the extraction sockets is
      described. Bone graft and a membrane are also required to augment the remainder
      of the extraction socket and provide maximum bone fill around the implant. The
      advantages, disadvantages, and indications for the procedure are described.

PMID- 12500871
TI  - Alternative to the inferior alveolar nerve block anesthesia when placing
      mandibular dental implants posterior to the mental foramen.
AB  - Local anesthesia block of the inferior alveolar nerve is routinely taught
      throughout dental education. This commonly used technique eliminates all
      somatosensory perception of the mandible, mandibular teeth, floor of the mouth,
      ipsilateral tongue, and all but the lateral (buccal) gingivae. Generally, the
      dentist or surgeon desires these structures to be anesthetized. However, in the
      placement of mandibular implants, it may be useful for the patient to be able to
      sense when the inferior alveolar nerve is in danger of being damaged, possibly
      producing permanent paresthesia. In this article, the technique of mandibular
      infiltration prior to mandibular implant placement in the mandible is discussed.

PMID- 12500872
TI  - Management of incision design in symphysis graft procedures: a review of the
      literature.
AB  - Symphysis graft procedures are being performed in clinical practice more
      frequently than ever before. Convenient surgical access, proximity of donor and
      recipient sites, low morbidity, availability of larger quantities of bone over
      other donor sites, minimal resorption, no hospitalization, and minimal discomfort
      are some advantages of this procedure over other intraoral sites. Three types of
      horizontal incisions can be performed during this procedure: the sulcular, the
      marginal, and the alveolar mucosal. Most studies regarding the chin graft
      technique are more concerned with the bone graft aspect than soft tissue
      management. Moreover, the criteria for the selected flap design appear to be
      based primarily on clinical experience or the same surgical approach regardless
      of interfacing factors. The periodontal status, amount of bone loss, periodontal
      risk of root fenestration, amount of keratinized gingiva, restorations in the
      gingival margin, and local musculature are some of the clinical findings that
      should be assessed to indicate the best incision design. In this review article,
      the advantages, disadvantages, indications, and contraindications of each
      incision design will be discussed.

PMID- 12500873
TI  - The implant Marshall plan.

PMID- 12500874
TI  - A new implant designed to maximize contact with trabecular bone: survival to 18
      months.
AB  - PROBLEM: A roughened, commercially pure titanium (CP-Ti) implant design has been
      developed that features a different length and pitch for each screw thread to
      direct functional stresses away from cortical bone and to the more resilient
      trabecular bone. Abutment-implant connection is made using a conical taper to
      provide a seal against invasion by microorganisms. PURPOSE: To assess short-term
      (18 months) clinical performance of this innovative implant design. METHODS: A
      total of 1,419 implants were placed in 313 patients to support 419 prostheses in
      a multidisciplinary, multicentered, prospective clinical study conducted by the
      Ankylos Implant Clinical Research Group (AICRG). More than 100 dentists at 32
      centers in the United States, 1 in Korea, and 1 in Taiwan are involved in the
      study. Failure was defined as implant removal for any reason. The influence of
      mobility at placement, implant length and diameter, incision type, augmentation,
      crestal bone reduction, bone density, and the use of the operating room or dental
      clinic on survival were evaluated over 18 months. Crestal bone loss between
      placement and uncovering was also determined. RESULTS: Crestal bone loss ranged
      from 0.2 to 0.5 mm. The overall success rate from placement to 18 months was
      96.6%. Implants mobile at placement failed more frequently (16.9%) compared with
      stable implants (3.1%). Wide-diameter implants and longer implants exhibited
      higher survival rates. Incision design and surgery location did not influence
      survival. Bone density was important to clinical survival.

PMID- 12500875
TI  - Effect of lipopolysaccharide contamination on the attachment of osteoblast-like
      cells to titanium and titanium alloy in vitro.
AB  - Failing implants with loss of alveolar bone are associated with gram-negative
      bacteria that carry lipopolysaccharide (LPS) in the bacterial cell wall. Bony
      regeneration around these implants is still an unpredictable procedure due to the
      many clinical factors involved. One important factor is the presence of
      contaminants such as LPS on the implant surface. The effect of implant-associated
      LPS on the attachment of bone cells to the implant surface is unknown. This
      project investigated the effect of LPS on the attachment of osteoblast-like cells
      (MC3T3-E1) to titanium and titanium alloy surfaces in vitro. We hypothesized that
      LPS would inhibit bone cell attachment either through loss of cellular attachment
      sites or alteration of cellular function. Three experimental approaches were
      used. First, alloy surfaces were exposed to LPS (100 microgram/mL) before the
      cells were allowed to attach. In the second approach, the cells were exposed to
      the LPS before they were allowed to attach. Last, the cells were allowed to
      attach before exposure to LPS. Cellular attachment to implant materials was
      measured by using a histochemical stain (MTT). The results indicated that LPS
      presence did not significantly (P > .05) alter osteoblast attachment to titanium
      or titanium alloy surfaces whether the exposure occurred before or after cellular
      adherence. It was concluded that LPS did not directly effect the attachment of
      the MC3T3-E1 osteoblasts to these implant surfaces in vitro. Further research is
      needed to define the clinical liabilities of LPS during implant placement and
      maintenance.

PMID- 12500876
TI  - A 48-month multicentric clinical investigation: implant design and survival.
AB  - This report is based on a total of 2,955 implants of 6 different designs,
      randomized and placed in 829 patients and followed for 48 months. Implant failure
      was defined as nonintegration at uncovering or removal due to mobility,
      persistent pain, infection, and evidence of radiographic bone loss. Failures were
      reported for 3 phases of treatment: implant placement to uncovering (phase 1),
      uncovering to loading (phase 2), and postloading (phase 3). Differences in
      survival were compared with Kaplan-Meier survival curves. The maxillary single
      tooth application resulted in 95.2% survival for the hydroxyapatite-coated
      grooved implants. In the maxillary completely edentulous application, survival of
      hydroxyapatite grooved and screw implants were considerably better compared with
      the titanium screw implants. The hydroxyapatite-coated cylinder had better
      survival than the titanium basket and screw designs in the mandibular completely
      edentulous application. The hydroxyapatite-coated cylinder and grooved implants
      in the maxillary posterior partially edentulous application had similar survival
      rates. The survival of the hydroxyapatite-coated cylinder exceeded that of the
      titanium basket in mandibular posterior partially edentulous applications.
      Analyses by phase of treatment indicated a pattern of early failure for
      nonhydroxyapatite-coated implants compared with hydroxyapatite-coated implants.
      The implant with the highest survival at all phases of treatment was the
      hydroxyapatite-coated press-fit cylinder. Two hydroxyapatite-coated implant
      designs performed well in the challenging posterior maxillary region.

PMID- 12500877
TI  - Extraction site reconstruction for alveolar ridge preservation. Part 1: rationale
      and materials selection.
AB  - Alveolar ridge resorption has long been considered an unavoidable consequence of
      tooth extraction. While the extent and pattern of resorption is variable among
      individuals, there is a progressive loss of ridge contour as a result of
      physiologic bone remodeling. Over the long term, prosthodontic complications,
      loss of function, and inadequate bone for the placement of dental implants may
      result. Guided bone regeneration techniques and the use of bone replacement
      materials have both been shown to enhance socket healing and modify the
      resorption process. This review describes the process of alveolar bone loss,
      materials for extraction site grafting, and proposed mechanisms for ridge
      preservation.

PMID- 12500878
TI  - Extraction site reconstruction for alveolar ridge preservation. Part 2: membrane
      assisted surgical technique.
AB  - Alveolar ridge resorption has long been considered an unavoidable consequence of
      tooth extraction. Guided bone regeneration techniques and the use of bone
      replacement materials have both been shown to enhance socket healing and to
      potentially modify the resorption process. This article will describe a surgical
      technique using textured, high-density polytetrafluoroethylene (PTFE) membrane
      and particulate bone replacement materials for graft containment and prevention
      of soft tissue ingrowth into healing extraction sites. The technique described
      does not require primary closure, facilitating the preservation of keratinized
      mucosa and gingival architecture.

PMID- 12500879
TI  - Stability of implants and natural teeth as determined by the Periotest over 60
      months of function.
AB  - Various methods for evaluating tooth mobility have been developed throughout the
      years, but their acceptance has been limited because of the subjectivity
      associated with their use. In recent years, the Periotest has been studied and
      used to evaluate the mobility of natural teeth and is claimed to b e potentially
      reliable in assessing the stability of the implant-bone interface. Few clinical
      implant studies have used natural teeth as controls to monitor changes in
      mobility associated with dental implants. The Dental Implant Clinical Research
      Group initiated a long-term clinical study in 1991 to assess the influence of
      design, application, and site of placement on clinical success and crestal bone
      height. As part of the study, Periotest values (PTVs) were recorded for 2,623 of
      the 2,998 implants placed and uncovered. For the statistical analysis, 2,623
      implants were tested at second-stage surgery, with the number of implants tested
      varying at each follow-up visit. Data were collected from investigators at 32
      study centers for periods ranging up to 60 months. A total of 975 natural teeth
      from 409 partially edentulous study subjects served as controls. FPVs on natural
      teeth and implants were combined, and the overall average Periotest values (OA
      PTVs) were compared with values for individual subjects. The effect of implant
      and natural tooth locations on mobility were evaluated and compared with each
      other. The combined OA-PTV for all natural teeth was +1.8 and the OA-PTV for all
      implants was -3.4 PTVs. Compared with those in the maxillae, mandibular teeth and
      implants were found to be more stable Implants were found to be significantly
      more stable as compared with natural teeth. The recorded variations in PTVs for
      natural teeth and implants over the entire evaluation period were not found to be
      significantly different. This study developed the following conclusions: (1)
      implants were found to be significantly less mobile as compared with natural
      teeth for individual subjects; (2) the PTVs for natural teeth and implants did
      not exhibit significant variation over the evaluation period; (3) the Periotest
      can provide reproducible assessment of stability in a long-term clinical study;
      and (4) changes in PTVs may be helpful in evaluating improvement or degradation
      of the implant-bone complex.

PMID- 12500880
TI  - Case report: use of an extraction site for implant placement.
AB  - This case report describes the use of an extraction site for placement of a
      critically important implant. This use solved an important functional and
      cosmetic problem in a dramatic and successful manner.

PMID- 12500881
TI  - How effectively do managed care organizations influence prescribing and
      dispensing decisions?
AB  - OBJECTIVE: To examine the extent to which managed care organizations (MCOs) use
      formularies, therapeutic interchange, and prior approval and to determine how
      effectively these tools influence prescribing and dispensing decisions. RESEARCH
      DESIGN: Literature review. PATIENTS AND METHODS: Studies relating to
      effectiveness were identified through a comprehensive literature review using the
      MEDLINE and International Pharmaceutical Abstracts databases. Only peer-reviewed
      studies done in outpatient settings were included. Studies measuring extent of
      use were taken primarily from published and widely available marketing research
      reports. RESULTS: Closed formularies were found to be effective in decreasing the
      utilization, but not necessarily the cost, of prescription drugs. Just under half
      of health maintenance organizations (HMOs) and 10% of employer-sponsored health
      plans use closed formularies. Prior approval programs have been shown to reduce
      use of target drugs and drug costs in a small number of drug classes. Nearly all
      HMOs and most employer-sponsored health plans use prior approval programs. How
      extensively the programs are used is not reported. About half of HMOs and
      employer-sponsored health plans use therapeutic interchange. Voluntary programs
      have been shown to be successful in staff-model HMOs. Mandatory, but not
      voluntary, programs have been shown to be successful in independent practice
      association-model HMOs. CONCLUSION: The literature indicates that most MCOs have
      had limited success using formularies, therapeutic interchange, and prior
      approval to influence prescribing and dispensing decisions. Although these tools
      have been effective in some situations, their impact has been limited by their
      low rate of utilization.

PMID- 12500882
TI  - Characteristics of eye care practices with managed care contracts.
AB  - OBJECTIVES: To describe the variation in practice structure, financial
      arrangements, and utilization and quality management systems for eye care
      practices with managed care contracts. STUDY DESIGN: Cross-sectional survey of 88
      group and 56 solo eye care practices that contract with 6 health plans affiliated
      with a national managed care organization. The survey contained modules on
      practice structure, financial arrangements, utilization management, and quality
      management. The survey response rate was 85%. RESULTS: Group practices with both
      ophthalmologists and optometrists were triple the size of ophthalmology-only
      groups, and 5 times the size of optometry-only groups. Fee-for-service payments
      were the primary source of group practice revenues, although 60% of groups
      derived some revenues from capitation payments. Group practices paid their
      physicians almost exclusively with fee-for-service payments or salary
      arrangements, with minimal capitation at the individual level. Almost no
      practices used both capitation and bonuses to compensate providers. Most
      practices received practice profiles and three fourths were subject to
      utilization review, which mainly consisted of preauthorization for procedures,
      tests, or referrals. Nearly all practices used clinical guidelines, protocols, or
      pathways in managing patients with diabetic retinopathy or glaucoma. Further,
      nearly all group practices used computerized information systems to assist in
      delivering care, and most had provider education programs. CONCLUSIONS: Managed
      care has affected the way eye care providers organize, finance, and deliver
      healthcare. In general, our findings paint an optimistic picture of eye care
      practices that contract with managed care organizations. Few practices bear
      substantial financial risk, and nearly all practices use quality management tools
      that could help to improve the quality of care.

PMID- 12500883
TI  - Enhancing the quality of care for patients with coronary heart disease: the
      design and baseline results of the hastening the effective application of
      research through technology (HEART) trial.
AB  - BACKGROUND: Effective therapies exist for reducing mortality in persons with
      coronary heart disease (CHD), but they remain underused. OBJECTIVE: To report the
      design and baseline results of a quality improvement project designed to increase
      the use of hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, beta
      adrenergic blocking agents, and angiotensin-converting enzyme (ACE) inhibitors in
      patients with CHD in a network-model managed care setting. METHODS: Patients with
      CHD were identified by searching a claims database. Use of therapies was assessed
      by linkage with a pharmacy benefits database. A survey was mailed to primary care
      physicians to collect information related to attitudes and behavioral intentions
      regarding aggressive management of CHD. An intervention, consisting of a
      guideline summary, performance feedback, and medical chart reminders, was
      evaluated in a randomized, practice-based trial. RESULTS: Among 1189 patients
      with CHD, the median prevalence of receipt of HMG-CoA reductase inhibitors, beta
      adrenergic blocking agents, and ACE inhibitors across practices at baseline (the
      first 3 months of 1999) was 50.0%, 35.0%, and 18.8%, respectively. Reported
      barriers included a perception that aggressive management of CHD is thought to be
      unimportant by support staff yet to require significant staff time. Aggressive
      management of CHD was perceived to incur non-reimbursable costs, to be
      unimportant in their patient population, to require a great deal of patient
      education and self-management, and to be limited because many patients do not
      adhere to therapy. CONCLUSIONS: Opportunities exist for enhancing the quality of
      care provided to patients with CHD. Our experience to date supports the
      logistical feasibility of implementing network-level quality enhancement efforts
      in managed care networks.

PMID- 12500884
TI  - Economic evaluation of enoxaparin as prophylaxis against venous thromboembolism
      in seriously ill medical patients: a US perspective.
AB  - OBJECTIVE: To determine the cost and cost effectiveness of adding venous
      thromboembolism (VTE) prophylaxis with enoxaparin, a low-molecular-weight
      heparin, to standard care for acutely ill, hospitalized medical patients.
      METHODS: A pharmacoeconomic model was developed to simulate the 6- to 14-day
      course of enoxaparin prophylaxis evaluated in the MEDENOX trial in a US
      healthcare setting. Clinical results as reported for the trial were applied to
      resource use and treatment costs in a US healthcare environment. The model
      projects hospital length of stay and cost for an acute medical admission from a
      third-party payer perspective, as well as costs for the course of enoxaparin.
      RESULTS: VTE prophylaxis with enoxaparin would account for 1.2% to 2.4% of the
      cost of a hospital admission, with an additional $23 +/- $28 to $99 +/- $122 to
      complete the course of prophylaxis out of hospital. Incremental cost
      effectiveness of VTE prophylaxis relative to no prophylaxis ranges from $1249 to
      $3088 per VTE avoided. Venous thromboembolism prophylaxis appears to be a break
      even intervention, with the cost recouped through avoided treatment, if the rate
      of treated VTE without prophylaxis is at least 3-4%. DISCUSSION AND CONCLUSIONS:
      The MEDENOX trial demonstrated that prophylaxis with enoxaparin substantially
      decreases the risk of VTE among acutely ill, hospitalized medical patients.
      Economic analysis indicates that this protection represents a small increase in
      current treatment costs. Prophylaxis is cost effective in terms of incremental
      cost per VTE avoided. Furthermore, there is a reasonable likelihood that the cost
      of prophylaxis will be offset by avoided future VTE treatment.

PMID- 12500885
TI  - When do developing countries adopt managed care policies and technologies? Part
      II: Infrastructure, techniques, and reform strategies.
AB  - OBJECTIVES: To specify the essential infrastructure elements required to
      implement managed care techniques successfully in a developing country, once the
      necessary macroeconomic preconditions for managed care have been met. Also, to
      describe how managed care techniques can be integrated into health system reform
      strategies. STUDY DESIGN AND METHODS: Analysis of available developing country
      health system and healthcare spending data, review of the available literature,
      and authors' experience evaluating healthcare reform in developing countries.
      RESULTS: Successful managed care relationships among payers, providers, and
      patients rely on several essential infrastructure elements: enabling legislation;
      regulatory mechanisms to administratively correct health and insurance market
      failures; enforceable contracts; and formal groups or associations of providers.
      Once these infrastructure elements are in place, a developing country government
      can consider implementing 1 or more managed care techniques, including payment
      strategies, demand-side techniques, and utilization management. CONCLUSIONS:
      Governments in many developing countries can take deliberate steps to accelerate
      the evolution of certain macroeconomic preconditions--human capital and
      information systems--and essential infrastructure elements necessary to support
      managed care techniques. They may then choose to experiment carefully with
      implementing specific managed care techniques, with consideration given to how
      the managed care techniques can promote primary care.

PMID- 12500887
TI  - Abortion and suicide.

PMID- 12500886
TI  - Profiling resource use: do different outcomes affect assessments of provider
      efficiency?
AB  - OBJECTIVES: To examine whether 2 outcome measures result in different assessments
      of efficiency across 22 service networks within the Department of Veterans
      Affairs (VA). STUDY DESIGN: A retrospective analysis using VA inpatient and
      outpatient administrative databases. METHODS: A 60% random sample of veterans who
      used healthcare services during fiscal year 1997 was split into a 40% sample (n =
      1,046,803) for development and a 20% sample (n = 524,461) for validation.
      Weighted concurrent case-mix models using adjusted clinical groups were developed
      to explain variation in 2 outcomes: "days of care"--the sum of a patient's
      inpatient and outpatient annual visit days, and "average accounting costs"--the
      sum of the average service costs multiplied by the units of service for each
      patient. Two profiling indicators were calculated for each outcome: an unadjusted
      efficiency index and an adjusted efficiency index. These indices were compared to
      examine network efficiency. RESULTS: Although about half the networks were
      identified as "efficient" before and after case-mix adjustment, assessments of
      individual network efficiency were affected by the adjustment. The 2 outcomes
      differed on which networks were efficient. For example, 4 networks that appeared
      as efficient based on days of care appeared as inefficient based on average
      costs. CONCLUSIONS: Assessments of provider efficiency across the 22 networks
      depended on the outcome measure used. Knowledge about the extent to which
      assessments of provider efficiency depend on the outcome measure used is an
      important step toward improved and more equitable comparisons across providers.

PMID- 12500888
TI  - Clinical evaluation of prior suicide attempts and suicide risk in psychiatric
      inpatients.
AB  - BACKGROUND: In practice psychiatrists rely on their own experience and intuition
      to evaluate the suicide potential of individual patients, but the algorithms for
      the decision-making process remain unclear. OBJECTIVES: (1) to establish models
      for the decision making process for evaluating suicide risk; (2) to simulate the
      impact of information concerning the number of previous suicide attempts on the
      clinician's ability to detect patients who performed medically serious suicide
      attempts (MSSAs). METHODS: Four decision models (linear, dichotomized,
      hyperbolic, and undifferentiated) depicting the influence of the number of
      previous suicide attempts on the clinician's recognition of MSSAs in 250
      psychiatric inpatients were elicited and tested by a series of discriminant
      analyses. RESULTS: The dichotomized model ("all or none") was found to be the
      most efficient in detecting medically serious suicide attempts. CONCLUSION: The
      "all or none" paradigm seems to be the most appropriate way to evaluate the
      weight of previous suicide attempts in the decision-making process identifying
      medically serious suicide attempt patients.

PMID- 12500889
TI  - Suicide after deployment in UN peacekeeping missions--a Danish pilot study.
AB  - This pilot study looks at the frequency of suicide among Danish soldiers who took
      part in the UN mandated forces (UNMF) during the 1990's. In a contingent of
      nearly 4000 Danish UN soldiers four suicides were documented, two of whom
      committed suicide less than one month before deployment and two who committed
      suicide within a year after discharge from mission. Contributing factors,
      prevention strategies, and implications for future research are discussed.

PMID- 12500890
TI  - Analysis of crisis intervention processes.
AB  - The remediation processes in psychosocial crisis intervention were modeled
      focusing on cognitive orientation. Frequent observations and subsequent process
      modeling constitute a novel approach to process research and reveal process
      outcome associations. A sample of 40 inpatients who were assigned to treatment in
      a crisis intervention unit was monitored in order to study the process of crisis
      intervention. The process data consisted of patients' self-ratings of the
      variables mood, tension, and cognitive orientation, which were assessed three
      times a day throughout hospitalization (M = 22.6 days). Linear time series models
      (vector autoregression) of the process data were computed to describe the
      prototypical dynamic patterns of the sample. Additionally, the outcome of crisis
      intervention was evaluated by pre-post questionnaires. Linear trends were found
      pointing to an improvement of mood, a reduction of tension, and an increase of
      outward cognitive orientation. Time series modeling showed that, on average,
      outward cognitive orientation preceded improved mood. The time series models
      partially predicted the treatment effect, notably the outcome domain "reduction
      of social anxiety," yet did not predict the domain of symptom reduction. In
      conclusion, crisis intervention should focus on having patients increasingly
      engage in outward cognitive orientation in order to stabilize mood, reduce
      anxiety, and activate their resources.

PMID- 12500891
TI  - Suicides and suicide attempts in emergency medicine.
AB  - OBJECTIVE: In emergency medicine, suicides and attempted suicides represent a
      major challenge for emergency physicians (EPs) and paramedics, both in terms of
      psychiatric and somatic treatment. To date no investigations have been performed
      to determine prevalence rates, method of suicide or attempted suicide, and the
      problems faced by EPs when treating these patients. This investigation presents a
      first evaluation of the complete emergency protocols from a major German city
      focusing on suicide and parasuicide. METHODS: A retrospective analysis of all EP
      protocols from 1995 in the city of Hamburg was performed. All protocols were
      evaluated with respect to suicide parasuicide and suicidal ideation. Demographic
      data and information on method of suicide or attempted suicide, severity of
      illness, and underlying psychiatric disorder were extracted from the protocols.
      RESULTS: A total of 26,347 emergency protocols were evaluated. Suicide and
      attempted suicide were considered either certain, probable, or possible in 743
      cases (2.8%). Suicide was committed in 171 cases and attempted were made by 572
      individuals. More men committed suicide in all age groups. By far the highest
      number of suicide attempts were by young men between 18 and 39 years of age.
      Hanging was the most commonly used method of completed suicide (41%), followed by
      jumping from a height (21%). The methods of intoxication with medication (54%)
      and illegal drugs (17%) clearly prevailed in suicide attempts. Documentation of
      suicides and attempted suicides was revealed to be unsatisfactory. Underlying
      psychiatric disorders were scarcely recorded. CONCLUSION: In emergency medicine,
      the incidence of suicide or the attempt to commit suicide is small, yet
      disturbing. The frequency assessed may be too low as result of methodology. There
      is a need to improve the education of emergency physicians and paramedics in this
      area, and there is a need for data to be collected in a prospective design.

PMID- 12500892
TI  - Acute carbon monoxide poisoning and alcohol intoxication: a rare condition that
      is complex to manage.
AB  - Since the changeover in the gas used in domestic appliances, the prevalence of
      acute carbon monoxide (CO) poisoning has been dramatically reduced. In suicide
      attempts with car exhaust fumes lies the most common cause of the disorder. As a
      consequence, patients are more complex to manage as they often have other
      associated diagnoses such as substance use disorder, depressive disorder, or long
      standing personality disorder. This report details such a case. The medical
      treatment was based on the carboxyhemoglobin (COHgb) levels at the time of
      admission. The patient developed permanent cognitive and functional deficits
      consistent with the observed brain scan changes. The author discusses the
      importance of an appropriate early diagnosis of the condition, the difficulties
      associated with it, and the validity of using the carboxyhemoglobin levels as a
      guide to treatment.

PMID- 12500893
TI  - Why has the antidepressant era not shown a significant drop in suicide rates?
AB  - Over the past decades the rate of completed suicide has remained quite stable,
      whereas that of suicide attempts seems to have increased (to the extent it has
      been studied in defined regions). These are puzzling observations, since
      depression is the major suicide precursor and and since antidepressants have been
      increasingly used over the years in the treatment of depression. These
      observations have not attracted sufficient attention, possibly because they do
      not accord with consensus opinions about depression treatment in psychiatry
      today. This paper discusses a number of possible explanations that not only
      deserve, but are definitely in need of systematic investigation.

PMID- 12500894
TI  - Emergency psychiatry and the suicidal patient.

PMID- 12500895
TI  - The death of suicidology? Letter across the Pacific.

PMID- 12500896
TI  - Guttman scaling national laws on suicide.

PMID- 12500897
TI  - Suicide in the new millennium--some sociological speculations.

PMID- 12500898
TI  - Contractile properties and myosin heavy chain isoform composition in single fibre
      of human laryngeal muscles.
AB  - In the present study we aimed to determine the functional properties and the
      myosin heavy chain (MHC) isoform composition of single chemically skinned fibres
      from the vocal muscle of four adult men (age: 55-67 years). Single fibres,
      dissected from the bioptic samples, were chemically skinned and isometric tension
      (P0) and maximal shortening velocity (V0) were measured at pCa 4.6. MHC and
      myosin light chain (MLC) composition of fibre segments and MHC distribution of
      the biopsy samples were analysed by SDS-poly-acrylamide gel electrophoresis (SDS
      PAGE) and densitometry. Four MHC isoforms (1, 2A, 2X and a fourth isoform,
      provisionally called L) and five MLC isoforms (MLC1s, MLC1f, MLC3f, MLC2f, MLC2s)
      were identified. The major findings of this study were: (1) fast MHC isoforms (in
      particular MHC-2A) and fast fibres were predominant, (2) one-third of the fibres
      were mixed or hybrid, i.e. expressed more than one MHC isoform, (3) V0 and P0
      values were determined by the MHC isoform composition and mixed fibres showed
      functional properties which were intermediate between pure fibres; MHC-L was
      associated with V0 values similar to those of MHC-2A, (4) compared with limb
      muscles, V0 values of laryngeal fibres were similar to those of limb muscle
      fibres containing the same MHC isoform whereas P0 values were lower for slow and
      fast 2X fibres and similar for fibres expressing MHC-2A.

PMID- 12500899
TI  - Role of K+ channels in L-6 myoblast migration.
AB  - Migration of myoblasts is an important component of the reparative response to
      muscle injury, and furthermore may be a key determinant of the success of
      myoblast transplantation for the treatment of genetic muscle diseases. The
      present study examined the hypothesis that K+ channels modulate myoblast
      migration. The migration of cultured L-6 myoblasts was assessed in vitro on
      confluent cultures with the razor wound method, in the absence and presence of
      the following agents: 3,4-diaminopyridine and tetraethylammonium (which block
      several types of K+ channels), apamin and charybdotoxin (which block Ca++
      activated K+ channels), glibenclamide (which blocks ATP-sensitive K+ channels),
      and alpha-, beta-, gamma-, and delta-dendrotoxin (which block voltage-gated K+
      channels). Migration was assessed with respect to number of migrated cells,
      average distance migrated, and total distance migrated. Overall, myoblast
      migration was stimulated in response to low concentrations of tetraethylammonium,
      apamin, glibenclamide, and alpha-, beta- and delta-dendrotoxin. With these
      agents, the number of migrated cells increased by 28-47%, the average distance
      migrated increased by 22-35%, and the total distance migrated increased by 60
      85%. Conversely, migration was inhibited by high concentrations of 3,4
      diaminopyridine, tetraethylammonium, and all dendrotoxins. These data indicate
      that in L-6 myoblasts migration is regulated by K+ channels, and that several
      types of K+ channels appear to participate in cell migration.

PMID- 12500900
TI  - Nebulin is a thin filament protein of the cardiac muscle of the agnathans.
AB  - Nebulin is an integral protein of skeletal muscle thin filaments and probably
      acts as a ruler for the thin filament length. Cardiac muscles of higher
      vertebrates have been shown earlier to lack nebulin. Instead in human and chicken
      cardiac muscle the much smaller protein nebulette replaces nebulin. Since
      nebulette is confined to the Z-disc region of the sarcomere and does not span the
      whole thin filament length, it must have functions significantly different from
      those assumed for nebulin. We have investigated nebulin in skeletal and cardiac
      muscles of the agnathans (lamprey, hagfish), elasmobranchs (shark), chondrosts
      (sturgeon) and teleosts (trout, eel) by SDS-PAGE and immunodetection methods.
      Among these, lamprey and hagfish cardiac muscles are unique in that both contain
      full-length nebulin identical in molecular mass to the nebulin of the respective
      body muscle. Using immunofluorescence microscopy, lamprey cardiac nebulin was
      localised in the I-band of the sarcomere, the same as for nebulin in skeletal
      muscle. In contrast to this, all gnathostome species investigated lacked nebulin
      in cardiac muscles, while it was present in the respective skeletal muscles. This
      clearly shows that nebulin is not exclusively present in skeletal muscles of
      chordates. The findings also demonstrate a rare case of dramatic size reduction
      of a protein during evolution.

PMID- 12500901
TI  - Partial fast-to-slow conversion of regenerating rat fast-twitch muscle by chronic
      low-frequency stimulation.
AB  - Chronic low-frequency stimulation (CLFS) of rat fast-twitch muscles induces
      sequential transitions in myosin heavy chain (MHC) expression from MHCIIb -->
      MHCIId/x --> MHCIIa. However, the 'final' step of the fast-to-slow transition,
      i.e., the upregulation of MHCI, has been observed only after extremely long
      stimulation periods. Assuming that fibre degeneration/regeneration might be
      involved in the upregulation of slow myosin, we investigated the effects of CLFS
      on extensor digitorum longus (EDL) muscles regenerating after bupivacaine-induced
      fibre necrosis. Normal, non-regenerating muscles responded to both 30- and 60-day
      CLFS with fast MHC isoform transitions (MHCIIb --> MHCIId --> MHCIIa) and only
      slight increases in MHCI. CLFS of regenerating EDL muscles caused similar
      transitions among the fast isoforms but, in addition, caused significant
      increases in MHCI (to approximately 30% relative concentration). Stimulation
      periods of 30 and 60 days induced similar changes in the regenerating bupivacaine
      treated muscles, indicating that the upregulation of slow myosin was restricted
      to regenerating fibres, but only during an early stage of regeneration. These
      results suggest that satellite cells and/or regenerating fast rat muscle fibres
      are capable of switching directly to a slow program under the influence of CLFS
      and, therefore, appear to be more malleable than adult fibres.

PMID- 12500902
TI  - 2,3-butanedione monoxime (BDM), a potent inhibitor of actin-myosin interaction,
      induces ion and fluid transport in MDCK monolayers.
AB  - Membrane-cytoskeleton interactions have been shown to be crucial to modulate
      polarity, cell shape and the paracellular pathway in epithelial MDCK cell
      monolayers. In particular, actin organization and myosin-dependent contractility
      play an important role in the regulation of these functions. Participation of
      myosin in vectorial transport, expressed as formation of domes, was investigated
      in confluent monolayers of high transepithelial electrical resistance (TER)
      plated on non-permeable supports. Cells exposed to 2,3-butanedione monoxime, a
      selective inhibitor of myosin ATPase, showed a remarkable increase in the number
      of domes. Replacement of extracellular Na+ and Cl- and inhibition of Na+-K+
      ATPase blocked the induction of domes. The monoxime also caused a reduction of
      the TER leading to an increase in the paracellular flux of small molecular weight
      dextran. However, immunofluorescence microscopy of drug-treated cells showed that
      the localization and staining pattern of tight junction proteins ZO-1, occludin,
      and claudin 1, or the actin-myosin ring at the zonula adherens, were not
      modified. Treatment with the drug produced striking re-arrangements of actin
      filaments at the microvilli and at the basal level of the cells. Our data show
      that disruption of actin-myosin interaction at several cellular sites contributed
      importantly to the increased transport activity and the formation of the domes.
      These results point to the relevant role or actin-myosin dynamics and actin
      organization in the regulation of ion and water channel activity in these cells.

PMID- 12500903
TI  - Differential expression of mutually exclusive exons of the fast skeletal muscle
      troponin T gene in the chicken wing and leg muscles.
AB  - To determine the physiological significance of developmentally regulated and
      muscle tissue-specific expression of troponin T (TnT) isoforms and also to
      elucidate mechanisms of alternative splicing, we investigated splicing patterns
      of fast skeletal muscle TnT by sequencing cDNAs obtained from the chicken wing
      and leg muscles. The chicken fast skeletal muscle TnT gene has 27 exons, and
      produces potentially 2(15) transcripts if alternative exons are randomly spliced.
      For the fourteen alternative exons in the 5'-region of the gene, we found 7 and
      12 splice variants in the wing biceps brachii and leg gastrocnemius,
      respectively. Out of 19, 12 variants were newly found in this study. Twenty two
      different splice variants were reported by the previous studies, but this number
      has now increased to 34 in the chicken TnT gene, suggesting that alternative
      splicing is not random, but strictly regulated. We also investigated splicing
      patterns of mutually exclusive exons 16 and 17 in the 3'-region of the gene.
      Approximately equal amounts of cDNAs containing exons 16 and 17 were detected in
      proximal regions of adult biceps brachii and gastrocnemius, respectively, whereas
      cDNA with exon 17 dominated in distal regions. Only cDNA containing exon 17 was
      found in both proximal and distal regions of 5-day-old gastrocnemius. The
      inclusion of exon 16 into cDNAs was detected in the proximal region of 15-day-old
      gastrocnemius and increased during development.

PMID- 12500904
TI  - Organization and distribution of intramuscular connective tissue in normal and
      immobilized skeletal muscles. An immunohistochemical, polarization and scanning
      electron microscopic study.
AB  - Collagen fiber network is a major contributor to the coherence and tensile
      strength of normal skeletal muscle. Despite the well-recognized importance of the
      intramuscular connective tissue to the normal integrity and function of the
      skeletal muscle, the specific architecture including the location and three
      dimensional orientation of the intramuscular connective tissue within the muscle
      tissue is poorly described. The structure of the intramuscular connective tissue
      was studied by immunohistochemistry, polarization microscopy (the crimp length
      and angle of the collagen fibers) and scanning electron microscope (SEM) in rat
      skeletal muscles (gastrocnemius, soleus and tibialis anterior) in normal
      situation and after 3 weeks of disuse (immobilization). Three separate networks
      of collagen fibers were distinguished by SEM in the normal endomysium; fibers
      running longitudinally on the surface of the muscle fibers (the main collagen
      orientation), fibers running perpendicularly to the long axis of the muscle
      fibers and having contacts with adjacent muscle fibers, and fibers attached to
      the intramuscular nerves and arteries. Similarly, the SEM analysis also disclosed
      three distinct collagen fiber networks running in different directions in the
      perimysium, but, contrary to the endomysium, the main fiber orientation could not
      be established. Immobilization resulted in a marked increase in the endo- and
      perimysial connective tissue, the majority of the increased endomysial collagen
      being deposited directly on the sarcolemma of the muscle cells. Immobilization
      also resulted in substantial increase in the number of perpendicularly oriented
      collagen fibers with contacts to two adjacent muscle fibers in the endomysium.
      Further, immobilization clearly disturbed the normal structure of the endomysium
      making it impossible to distinguish the various networks of fibers from each
      other. In the perimysium, immobilization-induced changes were similar, the number
      of longitudinally oriented collagen fibers was increased, the connective tissue
      was very dense, the number of irregularly oriented collagen fibers was markedly
      increased, and consequently, the different networks of collagen fibers could not
      be distinguished from each other. Of the three studied intact muscles, the crimp
      angle of the collagen fibers was lowest in the soleus and highest in the
      gastrocnemius muscle, and the crimp angle decreased over 10% in all muscles after
      the immobilization-period. Altogether, the above described quantitative and
      qualitative changes in the intramuscular connective tissue are likely to
      contribute to the deteriorated function and biomechanical properties of the
      immobilized skeletal muscle.

PMID- 12500906
TI  - Hepatic toxicity possibly associated with kava-containing products--United
      States, Germany, and Switzerland, 1999-2002.
AB  - Since 1999, health-care professionals in Germany, Switzerland, and the United
      States have reported the occurrence of severe hepatic toxicity possibly
      associated with the consumption of products containing kava (i.e., kava kava or
      Piper methysticum). A total of 11 patients who used kava products had liver
      failure and underwent subsequent liver transplantation. On March 25, 2002, in
      response to five such case reports (four in Europe and one in the United States),
      the Food and Drug Administration (FDA) issued a consumer advisory and
      subsequently completed an investigation already underway of a similar U.S. case.
      This report presents the investigation of the two U.S. cases of liver failure
      associated with kava-containing dietary supplement products and summarizes the
      European cases. FDA continues to advise consumers and health-care providers about
      the potential risk associated with the use of kava-containing products.

PMID- 12500907
TI  - Invasive cervical cancer among Hispanic and non-Hispanic women--United States,
      1992-1999.
AB  - During 1973-1999, both the incidence of and death rates for cervical cancer
      decreased approximately 50% in the United States. For 2002, approximately 13,000
      new cases of invasive cervical cancer are expected, and approximately 4,100 women
      will die of the disease. Although invasive cervical cancer can be prevented by
      regular screening, the prevalence of Papanicolaou (Pap) testing remains
      relatively low among minority populations such as Hispanic women. To characterize
      the incidence of invasive cervical cancer, CDC analyzed incidence data for
      Hispanic and non-Hispanic women during 1992-1999 in 11 geographic areas with
      population-based registries. This report summarizes the results of this analysis,
      which indicate that the incidence of invasive cervical cancer decreased for
      Hispanic and non-Hispanic women. However, among women aged > or = 30 years,
      cervical cancer incidence for Hispanic women was approximately twice that for non
      Hispanic women. To lower the incidence of invasive cervical cancer, local health
      organizations should provide culturally appropriate public health interventions
      that encourage participation in readily accessible cervical cancer-screening
      programs.

PMID- 12500905
TI  - Six and Eya expression during human somitogenesis and MyoD gene family
      activation.
AB  - This report describes the characterisation of the expression profile of several
      myogenic determination genes during human embryogenesis. The data were obtained
      from axial structures and limb buds of human embryos aged between 3 and 8 weeks
      of development. Using in situ hybridisation to detect Pax3 and MyoD gene family
      mRNAs, and immunochemistry to follow Six and Eya protein accumulation, we have
      been able to establish the chronology of accumulation of these gene products. As
      in mouse, the first transcripts detected in myotomes of 3 week-old embryos are
      Pax3 and Myf5, followed by the expression of myogenin. MyoD appears to be
      activated well after Myf5, myogenin and MRF4 in the early myotome, whereas, in
      limb bud muscles, the presence of all four of these mRNAs is concomitant from 6
      weeks. Six1, Six4 and Six5 homeoproteins are detected later than Myf5 activation.
      These Six homeoproteins are first observed in the cytoplasm of myogenin
      expressing cells. At later stages of development, Six1 and Six5, but not Six4,
      are translocated into the nuclei of myogenic cells, concomitantly with MyHCemb
      expression. Eya1 and Eya2 proteins, potential Six cofactors, were also detected
      in myogenin positive cells, but their accumulation was delayed and was mainly
      cytoplasmic. These results preclude that early activation of Myf5, myogenin and
      MRF4 is under the control of Six and Eya proteins, while Six and Eya proteins
      would be involved in later steps of myogenic differentiation.

PMID- 12500908
TI  - Progress toward poliomyelitis eradication--Ethiopia, Somalia, and Sudan, January
      2001-October 2002.
AB  - Since the World Health Assembly resolved in May 1988 to eradicate poliomyelitis,
      the estimated number of polio cases globally has declined >99%. The number of
      countries in which polio was estimated to be endemic decreased from 125 in 1988
      to 10 in 2001, and three World Health Organization (WHO) regions (American,
      European, and Western Pacific) comprising approximately 55% of the world's
      population have been certified polio-free. Ethiopia, Somalia, and Sudan have
      achieved the lowest levels of poliovirus circulation since the polio eradication
      initiative began and are approaching interruption of transmission. This report
      describes intensified polio eradication activities in these countries during
      January 2001-October 2002, summarizes progress made, and highlights remaining
      challenges. Continued political commitment and financial support will be required
      to eradicate polio in these countries.

PMID- 12500910
TI  - Occupational health indicators for tracking work-related health effects and their
      determinants.
AB  - Experts in various fields of public health have developed proposed indicators to
      enhance public health surveillance. These indicators have been published in
      Indicators for Chronic Disease Surveillance, June 2000, State Injury Indicator
      Report January 2002; and Draft Environmental Public Health Indicators, August
      2002. The indicators are measures of health or factors associated with health in
      specified populations.

PMID- 12500911
TI  - The pillars of a surgeon's life.

PMID- 12500912
TI  - Classification of subcapital hip fractures.

PMID- 12500913
TI  - Therapy for resectable gastric cancer: a practice guideline.

PMID- 12500914
TI  - Subcapital hip fractures: the Garden classification should be replaced, not
      collapsed.
AB  - OBJECTIVES: To evaluate rater agreement for a simple 2-category classification of
      subcapital hip fractures versus the 4-category Garden classification and to
      determine the effect of clinician experience on the level of agreement. SETTING:
      Sunnybrook and Women's Health Sciences Centre, Toronto, a level 1 trauma centre.
      METHOD: Eleven raters, with varying levels of clinical experience (3 fellowship
      trained orthopedic surgeons, 4 clinical fellows and 4 residents), classified 34
      pairs of anteroposterior and lateral radiographs of patients with subcapital hip
      fractures according to whether the fracture was stable (the fragments move as a
      unit) or unstable (the fragments move independently), and according to Garden's
      original 4-category classification. The exercise was repeated 1 month later. The
      radiographs were obtained from a fracture database to represent a wide spectrum
      of injury severity. OUTCOME MEASURES: The level of agreement beyond chance,
      quantified by use of the SAV statistic of O'Connell and Dobson. RESULTS: The most
      experienced raters demonstrated almost perfect inter- and intrarater agreement
      with respect to stable and unstable fractures (SAV > 0.80). The raters
      demonstrated only fair agreement for the Garden classification (mean SAV 0.64).
      Even junior clinicians demonstrated substantial agreement regarding fracture
      stability, with much lower scores for the Garden classification. Collapsing the
      Garden classification responses into 2 categories (stages I and II v. III and IV)
      was not synonymous with rater categorization of stable versus unstable.
      CONCLUSION: The Garden classification for subcapital hip fractures is unreliable
      and should be abandoned in favour of categorizing fractures as stable versus
      unstable.

PMID- 12500915
TI  - Hepatic alveolar echinococcosis: clinical report from an endemic region.
AB  - OBJECTIVE: To review the clinical management of alveolar echinococcosis. DESIGN:
      A retrospective analysis. SETTING: A university-affiliated hospital in Turkey.
      PATIENTS: Forty patients treated for alveolar echinococcosis between 1987 and
      2000. INTERVENTIONS: Curative resection followed by chemotherapy, or medical
      palliation with chemotherapy only. Palliative procedures such as bilioenteric or
      external drainage were done for cholestatic jaundice and liver abscess. OUTCOME
      MEASURES: Results of medical and surgical treatment. RESULTS: Seventeen patients
      had a resectable tumour and all underwent curative resection. Of the other 23
      patients with nonresectable tumour, 11 underwent palliative surgical procedures
      such as bilioenteric or external drainage for cholestatic jaundice or liver
      abscess. All patients received long-term albendazole therapy. Four patients with
      nonresectable tumour died because of chronic liver failure. In a 6.5-year follow
      up, there was no recurrence in patients who underwent curative resection. The
      efficacy of chemotherapy is limited in nonresectable disease. CONCLUSIONS: To
      increase the rate of early detection and curative resection, screening programs
      are essential. Research on new chemotherapeutic approaches should be made to
      improve survival in patients with nonresectable disease.

PMID- 12500916
TI  - A cost-effectiveness analysis of standard versus endovascular abdominal aortic
      aneurysm repair.
AB  - OBJECTIVE: To compare endovascular and standard open repair of abdominal aortic
      aneurysms in terms of initial in-hospital costs and the costs of secondary
      interventions and surveillance. DESIGN: A retrospective study. SETTING: A
      university-affiliated tertiary care medical centre. PATIENTS: Seven patients who
      underwent elective endovascular (EV) repair of an abdominal aortic aneurysm in
      1998 and 31 patients anatomically suitable for endovascular repair who underwent
      standard (STAN) elective repair. Follow-up ranged from 2 to 14 months.
      INTERVENTIONS: Elective repair of an abdominal aortic aneurysm with use of the
      standard technique or endovascular technology. OUTCOME MEASURES: Costs common to
      both groups were not determined. Costs were determined for total hospital stay,
      preoperative or postoperative embolization, grafts, additional endovascular
      equipment, and follow-up computed tomography. RESULTS: Groups were similar with
      respect to demographic data and aneurysm size (EV = 6.23 cm v. STAN = 6.05 cm).
      All patients were in American Society of Anesthesiologists class III or IV.
      Vanguar bifurcated grafts and extensions were used in the EV group. The total
      cost for both groups in Canadian dollars included: cost of stay (EV, 5.6 d,
      $2092.63 v. STAN, 10.7 d, $4449.19; p = 0.009); cost of embolization (EV, n = 3;
      $900/procedure); cost of follow-up CT (EV, 5.4 per patient; $450/CT); cost of
      grafts (EV = $8571.43, STAN = $374); additional radiologic equipment costs (EV =
      $1475). The mean total cost differed significantly between the 2 groups (EV =
      $14,967.63 v. STAN = $4823.19; p = 0.004). The additional cost associated with a
      reduction in hospital stay was calculated by determining the incremental cost
      effectiveness ratio (ICER, difference in mean costs/difference in mean length of
      stay = $1604.51). CONCLUSIONS: Endovascular repair continues to be more expensive
      than standard open repair determined according to procedural and follow-up costs.
      The technology is still in the developmental stage, but as it evolves and follow
      up protocols are streamlined, it is hoped that there will be an eventual
      reduction in the costs associated with the endovascular procedure.

PMID- 12500917
TI  - Factors associated with the high cost of liver transplantation in adults.
AB  - OBJECTIVES: To determine the overall direct cost of liver transplantation in
      Canadian adults and to identify the factors that are associated with high cost.
      METHODS: The direct cost of liver transplantation from the perspective of third
      party payers was determined in a retrospective analysis of data from hospital
      charts and databases. A consecutive series of 119 adults who underwent liver
      transplantation between 1991 and 1992 was followed from the date of listing for
      transplantation to the second anniversary of the transplant. Patient-specific
      services during the pre-transplantation, transplantation and post-transplantation
      phases were compiled and costed. The primary consideration was the impact of
      complications on the cost of transplantation. Secondary considerations were the
      impact of age, sex of the patient, diagnosis and severity of liver disease on the
      total cost. RESULTS: The overall mean measured cost of liver transplantation was
      Can$89,066 (range from Can$30,505-Can$690,431). The multivariate logistic
      regression model for overall costs revealed that severe liver disease (OR =
      11.97), cytomegalovirus infection (OR = 6.12), additional operative procedure (OR
      = 4.22) and biliary complications (OR = 5.00) were associated with an increased
      likelihood of high cost. The addition of services that were not measured in the
      present analysis increased the total overall cost to a mean of $121,732 (1998
      Canadian dollars, follow-up costs discounted and inflation adjusted).
      INTERPRETATION: The factors that were associated with high cost of liver
      transplantation in Canadian adults were advanced liver disease, postoperative
      cytomegalovirus infection, the requirement for additional operative procedures
      and biliary complications.

PMID- 12500918
TI  - SESAP question. Endoscopic ultrasound (EUS) is superior to computed tomographic
      (CT) scanning for detecting the T and N stage of esophageal tumors.

PMID- 12500919
TI  - Medical management of osteoid osteoma.
AB  - OBJECTIVE: To see if the results of managing osteoid osteoma with medical
      treatment alone is comparable to those after surgery or other ablative therapy.
      DESIGN: A case series. SETTING: A tertiary care centre. PATIENTS: Eleven patients
      with osteoid osteoma treated over a 5-year period. The condition was diagnosed
      from a typical history, patient age, standard radiography, computed tomography,
      bone scanning, complete blood count and measurement of the erythrocyte
      sedimentation rate. INTERVENTIONS: Continued medical treatment with nonsteroidal
      anti-inflammatory drugs (NSAIDs) for 6 months after pain ceased. Surgery was done
      only in those who refused or could not tolerate medical treatment. MAIN RESULTS:
      Medical treatment successfully controlled the pain in all patients. Two patients
      decided to undergo surgery because of intolerance to the NSAIDS. In 7 patients
      the symptoms resolved after a mean time of 2.5 years. Two patients were still
      taking NSAIDS 5 years from the time of diagnosis. CONCLUSIONS: The natural
      history of osteoid osteoma is self-limited so patients should be offered
      nonoperative treatment, reserving ablative treatment for those who are unable or
      unwilling to take NSAIDs until their symptoms resolve.

PMID- 12500920
TI  - Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice
      guideline.
AB  - OBJECTIVE: To make recommendations on the use of neoadjuvant or adjuvant therapy
      in addition to surgery in patients with resectable gastric cancer (T1-4, N1-2,
      M0). OPTIONS: Neoadjuvant or adjuvant treatments compared with "curative" surgery
      alone. OUTCOMES: Overall survival, disease-free survival, and adverse effects.
      EVIDENCE: The MEDLINE, CANCERLIT and Cochrane Library databases and relevant
      conference proceedings were searched to identify randomized trials. VALUES:
      Evidence was selected and reviewed by one member of the Cancer Care Ontario
      Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site
      Group and methodologists. A systematic review of the published literature was
      combined with a consensus process around the interpretation of the evidence in
      the context of conventional practice, to develop an evidence-based practice
      guideline. This report has been reviewed and approved by the Gastrointestinal
      Cancer Disease Site Group, comprising medical oncologists, radiation oncologists,
      surgeons, a pathologist and 2 community representatives. BENEFITS, HARMS AND
      COSTS: When compared with surgery alone, at 3 years adjuvant chemoradiotherapy
      has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to
      improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has
      been shown to increase overall survival by 11.6% (40% v. 28.4%) and to improve
      relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated
      with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3
      [Southwest Oncology Group toxicity scale] are hematologic (54%), gastrointestinal
      (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation
      fields used can possibly damage the left kidney, resulting in hypertension and
      other renal problems. Furthermore, this therapy could increase the demand on
      radiation resources. Physicians and patients should understand the tradeoffs
      between survival benefit and toxicity and cost before making treatment decisions.
      RECOMMENDATIONS: After surgical resection, patients whose tumours have penetrated
      the muscularis propria or involve regional lymph nodes should be considered for
      adjuvant combined chemoradiotherapy. The current standard protocol consists of 1
      cycle of 5-fluorouracil (5-FU) (425 mg/m2 daily) and leucovorin (20 mg/m2 daily)
      administered daily for 5 days, followed 1 month later by 45 Gy (1.8 Gy/d) of
      radiation given with 5-FU (400 mg/m2 daily) and leucovorin (20 mg/m2 daily) on
      days 1 through 4 and the last 3 days of radiation. One month after completion of
      radiation, 2 cycles of 5-FU (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) in
      a daily regimen for 5 days are given at monthly intervals. There is no evidence
      on which to make a recommendation for patients with node-negative tumours that
      have not penetrated the muscularis propria. For patients unable to undergo
      radiation, adjuvant chemotherapy alone may be of benefit, particularly for those
      with lymph-node metastases. The optimal regimen remains to be defined. There is
      insufficient evidence from randomized trials to recommend neoadjuvant
      chemotherapy, or neoadjuvant or adjuvant radiotherapy or immunotherapy, either
      alone or in combination, outside a clinical trial. VALIDATION: A draft version of
      this document was circulated to 166 clinicians using a 21-item feedback
      questionnaire. Ninety-nine (63%) returned the questionnaire, and 74 of these
      indicated that the guideline was relevant to their clinical practice and
      completed the survey. Of the 74 clinicians, 52 (70%) agreed that the document
      should be approved as a practice guideline. SPONSORS: The CCOPGI is supported by
      Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

PMID- 12500921
TI  - Soft-tissue images. Ingestion of a knife into the right mainstem bronchus.

PMID- 12500922
TI  - Musculoskeletal case 25. Morton's neuroma.

PMID- 12500923
TI  - Soft-tissue case 48. Gallstone abscess.

PMID- 12500924
TI  - Canadian Association of General Surgeons Evidence Based Reviews in surgery. 4.
      Decision analysis of total thyroidectomy versus thyroid lobectomy in low-risk,
      differentiated thyroid cancer.

PMID- 12500925
TI  - Three-dimensional imaging for the surgical treatment of idiopathic scoliosis in
      adolescents.
AB  - Scoliosis is not simply a lateral deviation of the spine but is a complex
      deformity of the entire trunk. Recent advances in 3-dimensional (3-D) imaging
      have improved our understanding of the 3-D nature of adolescent idiopathic
      scoliosis (AIS) and have resulted in the development of a new generation of
      spinal instrumentation. Stereophotogrammetry, computed tomography, magnetic
      resonance imaging and surface topography all have their specific 3-D applications
      and relevance in the clinical management of AIS. In the near future, novel 3-D
      imaging applications will provide tools to guide the surgeon in the planning,
      performance and evaluation of increasingly sophisticated and less invasive
      surgical procedures, thus improving the outcome of surgical treatment for AIS.

PMID- 12500926
TI  - Mesenteric paraganglioma.

PMID- 12500927
TI  - Nontraumatic massive hemoperitoneum from melanoma metastatic to the uterus.
AB  - We have reported a case of nontraumatic massive hemoperitoneum caused by melanoma
      metastatic to the uterus that was readily managed with surgery. We believe this
      strategy provided effective palliation, improved quality of life and potentially
      prolonged survival for this patient.

PMID- 12500928
TI  - Tracheal necrosis after thyroidectomy.

PMID- 12500929
TI  - Ki-67 immunostaining activity is higher in positive axillary lymph nodes than in
      the primary breast tumor.
AB  - BACKGROUND: The monoclonal antibody Ki-67 allows to investigate the proliferative
      activity of tumor and is a clinically useful marker to characterize breast
      cancer. In this study, we have compared Ki-67 activity in 38 primary breast
      tumors and in their respective positive axillary lymph nodes (ALNs). METHODS:
      Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in
      38 nodes positive breast carcinomas and in their respective positive ALNs.
      Statistical analysis was performed with the Student's t-test (2-tailed) for
      equality of means. RESULTS: The proliferation index measured by Ki-67 expression
      was significatively higher (p < 0.02) in ALN than in the primary tumor (29.8%
      v.s. 21.8%). CONCLUSION: These results strongly suggest a higher proliferation
      and perhaps aggressivity of metastatic neoplastic cells when compared with their
      respective primary tumor. Perhaps, in the future, these differences in
      proliferation behavior might be taken into account when considering the choice of
      the adjuvant therapy.

PMID- 12500930
TI  - Dietary intake of selected fatty acids, cholesterol and carotenoids and estrogen
      receptor status in premenopausal breast cancer patients.
AB  - Although a wealth of research has focused on the influence of diet on breast
      cancer risk, the relationships between dietary factors and tumor characteristics
      of breast cancer, like estrogen receptor (ER) status, are not well characterized.
      In a case-case study, we evaluated self-reported dietary intake for five
      individual carotenoids, selected fatty acids, and cholesterol 1 year before
      diagnosis in 34 premenopausal breast cancer patients with ER-negative tumors and
      86 premenopausal breast cancer patients with ER-positive tumors from The
      University of Texas M. D. Anderson Cancer Center. In multivariate logistic
      regression analysis adjusted for age, body mass index, and ethnicity, high
      intakes of linoleic acid were associated with more than a threefold greater risk
      of ER-negative disease than ER-positive disease (odds ratio (OR) = 3.48, 95%
      confidence interval (CI) = 1.42-8.54), whereas high cholesterol intake was
      associated with lower risk of ER-negative disease (OR = 0.35, 95% CI = 0.14
      0.92). In a model evaluating carotenoids, selected fatty acids, and cholesterol
      together, the association with high intake of linoleic acid remained
      statistically significant (OR = 3.96,95% CI = 1.53-10.25), while those for high
      intake of cholesterol (OR = 0.38, 95% CI = 0.14-1.03) and low intake of
      cryptoxanthin (OR = 0.43, 95% CI = 0.17-1.06) were of marginal significance.
      While no striking associations were observed for the intakes of total
      carotenoids, selected fatty acids, and cholesterol, our analysis revealed an
      association for the consumption of a specific fatty acid (i.e., linoleic acid),
      suggesting dietary influence of this factor on ER status in premenopausal breast
      cancer patients. However, larger studies are needed to clarify the role of
      micronutrients in ER status in breast cancer.

PMID- 12500931
TI  - Radiation dose, chemotherapy and risk of lung cancer after breast cancer
      treatment.
AB  - It is of particular concern to evaluate the risk of lung cancer occurrence after
      breast cancer treatment as women with breast cancer quite often undergo radiation
      therapy as part of their initial treatment and their life expectancy remains
      long. From a roster of 7711 women initially treated for breast cancer between
      1954 and 1984, a cohort-study was performed among 4171 1-year survivors followed
      during the period 1975-1995. The relationship between the radiation dose received
      by the lung and the risk of lung cancer was then evaluated in a nested case
      control study of 11 breast-cancer patients who developed lung cancer and 22
      controls matched for age at diagnosis of breast cancer, period of initial
      treatment and length of follow-up. Among the 4171 women, six developed lung
      cancer during the entire follow-up as compared to 5.4 cases expected (SIR = 1.1,
      95% CI: 0.4-2.3). When considering only the women initially treated by
      radiotherapy with or without adjunction of chemotherapy and excluding the 10
      first years of follow-up, the SIR was significantly increased (SIR = 3.2, 95%CI:
      1.0-7.4). In the case-control study, nine of the 11 lung cancers occurred in the
      ipsilateral lung and two in the trachea. The overall odds ratio (OR) of lung
      cancer associated with initial radiotherapy was 1.4 (95% CI: 0.2-11.1) and an
      excess in the OR of 7% (90% CI: ? to 41%, p = 0.10) per gray delivered to the
      site of lung cancer was evidenced. Our results agree with previous studies in
      favor of an increased risk of lung cancer after radiation therapy for breast
      cancer.

PMID- 12500932
TI  - Amplified centrosomes in breast cancer: a potential indicator of tumor
      aggressiveness.
AB  - Molecular mechanisms leading to genomic instability and phenotypic variation
      during tumor development and progression are poorly understood. Such instability
      represents a major problem in the management of breast cancer because of its
      contribution to more aggressive phenotypes as well as chemoresistance. In this
      study we analyzed breast carcinomas and tumor-derived cell lines to determine the
      relationship between centrosome amplification and established prognostic factors.
      Our results show that centrosome amplification can arise independent of ER or p53
      status and is a common feature of aneuploid breast tumors. Centrosome
      amplification is associated with mitotic spindle abnormalities in breast
      carcinomas and thus may contribute to genomic instability and the development of
      more aggressive phenotypes during tumor progression.

PMID- 12500933
TI  - Shoulder movement after breast cancer surgery: results of a randomised controlled
      study of postoperative physiotherapy.
AB  - Breast screening programmes have facilitated more conservative approaches to the
      surgical and radiotherapy management of women diagnosed with breast cancer. This
      study investigated changes in shoulder movement after surgery for primary,
      operable breast cancer to determine the effect of elective physiotherapy
      intervention. Sixty-five women were randomly assigned to either the treatment
      (TG) or control group (CG) and assessments were completed preoperatively, at day
      5 and at 1 month, 3, 6, 12 and 24 months postoperatively. The CG only received an
      exercise instruction booklet in comparison to the TG who received the
      Physiotherapy Management Care Plan (PMCP). Analyses of variance revealed that
      abduction returned to preoperative levels more quickly in the TG than in the CG.
      The TG women had 14 degrees more abduction at 3 months and 7 degrees at 24
      months. Functional recovery at 1 month was greater in those randomised to the TG,
      with a dominant operated arm (OA) or receiving breast-conserving surgery.
      However, it was not possible to predict recovery over the 2 years postoperatively
      on the basis of an individual woman's recovery at 1 month postoperatively. The
      eventual recovery of abduction or flexion range of movement was not related to
      the dominance of the OA nor to the surgical procedure performed. The PMCP
      provided in the early postoperative period is effective in facilitating and
      maintaining the recovery of shoulder movement over the first 2 years after breast
      cancer surgery.

PMID- 12500934
TI  - Physiotherapy after breast cancer surgery: results of a randomised controlled
      study to minimise lymphoedema.
AB  - The development of secondary arm lymphoedema after the removal of axillary lymph
      nodes remains a potential problem for women with breast cancer. This study
      investigated the incidence of arm lymphoedema following axillary dissection to
      determine the effect of prospective monitoring and early physiotherapy
      intervention. Sixty-five women were randomly assigned to either the treatment
      (TG) or control group (CG) and assessments were made preoperatively, at day 5 and
      at 1, 3, 6, 12 and 24 months postoperatively. Three measurements were used for
      the detection of arm lymphoedema: arm circumferences (CIRC), arm volume (VOL) and
      multi-frequency bioimpedance (MFBIA). Clinically significant lymphoedema was
      confirmed by an increase of at least 200 ml from the preoperative difference
      between the two arms. Using this definition, the incidence of lymphoedema at 24
      mo. was 21%, with a rate of 11% in the TG compared to 30% in the CG. The CIRC or
      MFBIA methods failed to detect lymphoedema in up to 50% of women who demonstrated
      an increase of at least 200 ml in the VOL of the operated arm compared to the
      unoperated arm. The physiotherapy intervention programme for the TG women
      included principles for lymphoedema risk minimisation and early management of
      this condition when it was identified. These strategies appear to reduce the
      development of secondary lymphoedema and alter its progression in comparison to
      the CG women. Monitoring of these women is continuing and will determine if these
      benefits are maintained over a longer period for women with early lymphoedema
      after breast cancer surgery.

PMID- 12500935
TI  - Fertility cycle influence on surgical breast cancer cure.
AB  - Cancer growth and spread is an intricate process dependent upon both tumor and
      host. This laboratory is interested in the role of the fertility cycle,
      specifically cyclic changes in steroid hormone levels, in tumor growth and
      metastases. Our previous studies, using a murine model, have documented that
      breast cancer growth rate and post-resection metastatic behavior each change
      reproducibly during the estrous cycle, and that post-resection cancer spread
      depends upon the time within the estrous cycle that an advanced transplanted
      cancer is resected. Twelve to thiry-two percent cure rates were seen in these
      studies. That early work described estrous cycle stages just prior and near to
      putative ovulation to be superior while those stages farther from ovulation were
      disadvantageous times for surgery. Data presented here confirm the role of the
      estrous cycle in post-resection metastatic spread. This current work validates
      vaginal smear determined estrous cycle stage with uterine weight. A primary,
      transplantable, mammary carcinoma, which metastasizes to the lungs, was resected
      for surgical cure in cycling C3HeB/FeJ female mice at each fertility cycle stage.
      A group of oophorectomized (ovx) animals was also used. In two large, independent
      studies resecting much earlier stage cancers than in prior studies, a 96%
      surgical cure frequency was documented when the tumor is resected during estrus.
      The second best surgical cure rate is achieved when tumors are resected during
      metestrus (79% overall cure rate). Cure frequency in ovx animals is intermediate.
      These results further support a probable role for circulating E2 and P4 levels in
      modulating the metastatic process. We conclude that the timing of surgical
      resection within the estrous cycle affects the cancer's metastatic potential and
      that the optimal timing of resection may also depend to some extent upon the size
      (stage) of the resected cancer.

PMID- 12500936
TI  - Doxycycline-inducible expression of SPARC/Osteonectin/BM40 in MDA-MB-231 human
      breast cancer cells results in growth inhibition.
AB  - SPARC (secreted protein acidic and rich in cysteine)/BM40/Osteonectin is a
      matricellular protein with multiple effects on cell behaviour. In vitro, its
      major known functions are anti-adhesive and anti-proliferative, and it is
      associated with tissue remodelling and cancer in vivo. SPARC is overexpressed in
      many cancers, including breast cancer, and the effects of SPARC seem to be cell
      type-specific. To study the effects of SPARC on breast cancer, we transfected
      SPARC into the MDA-MB-231 BAG, human breast cancer cell line using the Tet-On
      inducible system. By western analysis, we found low background levels in the MDA
      MB-231 BAG and clone X parental cells, and prominent induction of SPARC protein
      expression after doxycycline treatment in SPARC transfected clones X5, X21, X24
      and X75. Induction of SPARC expression did not affect cell morphology or
      adhesiveness to collagens type I and IV, but it slowed the rate of proliferation
      in adherent cultures. Cell cycle analysis showed that SPARC slowed the
      progression to S phase. Doxycycline induction of SPARC also slowed the rate of
      monolayer wound closure in the cultured wound healing assay. Thymidine inhibition
      of proliferation abrogated this effect, confirming that it was due to anti
      proliferation rather than inhibition of migration. Consistent with this, we were
      unable to detect any differences in migration and Matrigel outgrowth analysis of
      doxycycline-stimulated cells. We conclude that SPARC is inhibitory to human
      breast cancer cell proliferation, and does not stimulate migration, in contrast
      to its stimulatory effects reported for melanoma (proliferation and migration)
      and glioma (migration) cells. Similar growth repression by SPARC has been
      reported for ovarian cancer cells, and this may be a common feature among
      carcinomas.

PMID- 12500937
TI  - Why and how post-mastectomy edema should be quantified in patients with breast
      cancer.
AB  - In the present study, we advocate quantifying post-mastectomy edema in patients
      with breast cancer in millilitres and not in centimetre, contrarily to the usual
      routine practice. The water displacement and perimetric quantification methods
      exhibited both excellent reproducibility with an intraclass correlation
      coefficient > 0.99 and an accuracy coefficient < 0.3%.

PMID- 12500938
TI  - Role of the Crumbs complex in the regulation of junction formation in Drosophila
      and mammalian epithelial cells.
AB  - The formation of a belt-like junctional complex separating the apical from the
      lateral domain is an essential step in the differentiation of epithelial cells.
      Thus protein complexes regulating this event are of first importance for the
      development of cell polarity and physiological functions of epithelial tissues.
      In Drosophila, the discovery of a gene, crb, controlling the coalescence of the
      spots of zonula adherens (ZA) into a adhesive ring around the cells was a major
      step. We know now that Crumbs, the product of crb is an apical transmembrane
      protein conserved in mammals and that it interacts by its cytoplasmic domain with
      two cortical modular proteins, Stardust (Sdt) and Discs lost (Dlt) that are also
      essential for the correct assembly of the ZA. These two proteins are also
      conserved in mammals and it is most likely that the Crumbs complex plays a
      similar role in very different species. Recently, we have shown that Crumbs
      interacts with the cortical cytoskeleton made of DMoesin and beta heavy-Spectrin
      and this connection could explain in part the role of Crumbs in building the ZA.
      Future work will help to understand several aspects of the Crumbs complex that
      are still unknown, like the role of the large extracellular domain or the precise
      function of Sdt and Dlt in the building of the ZA. Finding an answer to these
      questions will help to find new therapies for Retinitis pigmentosa and other
      retina degeneration in which CRB1, the human homologue of crb, has been involved.

PMID- 12500939
TI  - Cadherin-based cell adhesion in neuromuscular development.
AB  - The organisation and differentiation of striated skeletal muscles and their
      innervation is a particularly complex process implicating cells of mesodermic
      (myoblasts and fibroblasts) and neuroectoderrmic origin (neurons and glial
      cells). Myogenic and motor neuron precursors, the two major cell types
      participating in the formation of the neuromuscular axis, migrate, segregate,
      reassociate and differentiate in a coordinated fashion. The subsequent
      organisation of muscle cells and the establishment of muscle innervation rely on
      a complex tissular and cellular architectural organisation, which cannot be
      understood without taking into account juxtacrine cell interactions, and
      especially cell adhesion. Cell adhesion receptors of the cadherin family are
      widely expressed and dynamically regulated in space and time throughout
      neuromuscular development. A single cell expresses in general more than one
      cadherin at its surface and it is the combination of these molecules and their
      level of expression that determine their action within a given cell population.
      We focused in this review on the expression and roles of classical cadherins in
      relation to muscle cell and motoneuron differentiation. We also review the latest
      results on the mode of action of cadherins allowing to propose cellular and
      molecular cues on the mechanisms by which these cell adhesion receptors control
      muscle and neuronal cell shape, migration and differentiation.

PMID- 12500940
TI  - F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and
      myelination.
AB  - A general feature of the cell adhesion molecules belonging to the immunoglobulin
      family (Ig-CAMs) is to display a modular structure that provides a framework for
      multiple binding sites for other recognition molecules. Among this family,
      F3/contactin is a glycan phosphatidyl-inositol (GPI)-anchored molecule expressed
      by neurons that displays the distinctiveness to exert heterophilic but no
      homophilic binding activities. The Ig domains of F3/contactin were shown to
      interact with the L1 family of Ig-CAMs, including L1, NrCAM, and neurofascin.
      Binding between F3/contactin and NrCAM is known to modulate axonal elongation of
      the cerebellar granule cells and to control sensory axon guidance. F3/contactin
      mediates neuron-glial contacts through its association with extracellular matrix
      components (tenascin-R, tenascin-C) and RPTPbeta/phosphacan, influencing axonal
      growth and fasciculation. Another major role of F3/contactin is to organize
      axonal subdomains at the node of Ranvier of myelinated fibers in interplay with
      other Ig-CAMs, through its binding with caspr/paranodin at paranodes and the
      voltage-gated sodium channels in the nodal region. The F3/contactin deficient
      mice display a severe ataxia correlated with defects in axonal and dendritic
      projections in the cerebellum. These mice also display defects in nerve influx
      conduction due to the disruption of the axo-glial contacts at paranodes. Finally,
      the recent identification of a Drosophila homologue of F3/contactin indicated
      that this family of GPI-anchored CAMs plays a conserved function in axonal
      insulation.

PMID- 12500941
TI  - Dynamic aspects of cadherin-mediated adhesion in synapse development and
      plasticity.
AB  - Cadherins are calcium-dependent cell adhesion molecules that are enriched at
      synapses. Recent studies indicate important functional roles in synaptic
      targeting during brain development, and in regulating functional and structural
      aspects of synaptic plasticity and neural repair throughout life.

PMID- 12500942
TI  - The immunological synapse: the more you look the less you know...
AB  - Before T cells of the immune system can recognize pathogens, antigen presenting
      cells (APCs) must process pathogen-derived peptides and present them together
      with major histocompatibility complex molecules (MHC) to T lymphocytes. T
      lymphocytes then scan the surface of APCs and antigen-specific activation of the
      T cell will happen after interaction of T cell antigen receptor (TCR) with MHC
      peptide complexes expressed at the membrane of APCs. This interaction takes place
      in a nanometer scale gap between the two cells, referred to as an immunological
      synapse. Recent three-dimensional fluorescence analysis of this synapse revealed
      a dynamic spatial organization of membrane receptors, cytoskeleton and
      intracellular signaling complexes on the T cell side showing specific patterns,
      which depend on the nature of the T cell:APC pair. Although it is obvious that
      establishment of an intimate contact between T cells and APCs will facilitate
      cell:cell communication it is not clear what is the role, if any, of this
      receptors patterning. This molecular reorganization has long been thought to
      enhance and/or sustain TCR signaling and thus T cell activation, but this is now
      a matter of controversy. Moreover, mechanisms controlling immunological synapse
      formation are still unraveled. Segregation of proteins may occur spontaneously as
      proposed by mathematical modeling taking into account membrane fluidity, protein
      size and receptor/ligand affinity. Alternatively patterning of the molecules at
      the cell:cell interface could be driven by active processes involving T cell
      signaling and/or specific features of the APC. These different questions will be
      discussed herein.

PMID- 12500943
TI  - Dolichos biflorus agglutinin-binding site expression in basal keratinocytes is
      associated with cell differentiation.
AB  - A basal layer of squamous epithelia such as epidermis contains stem cells,
      transit amplifying cells as well as postmitotic differentiating cells. A detailed
      knowledge of the transition among these cell types in the course of epidermal
      renewal is important. It would help in better understanding of many pathological
      processes, including cancer, and in employment of epidermal cells for therapeutic
      purposes. In this study we analyzed the possible role of Dolichos biflorus
      agglutinin (DBA)-reactive alpha-N-acetylgalactosamine glycosylation in behavior
      of the human epidermal basal cells under in vivo and in vitro conditions. The
      data received from porcine epidermis were also included. Part of basal cells was
      positive for DBA-binding sites and these cells exhibited a lower presence of
      beta1 integrin in their basal surface connected to the basement membrane. The
      perinuclear Golgi-like accumulation of beta1 integrin was observed in some
      cultured keratinocytes. The co-localization of integrin with DBA-binding sites
      and 58 kDa protein suggests that alpha-N-acetylgalactosamine glycosylation could
      be related to beta1 integrin retention in the endoplasmatic reticulum Golgi
      intermediate compartment (ERGIC) at the beginning of the secretory pathway. The
      lack of anchorage in culture elevated the number of DBA-binding site positive
      cells without significant influence on cell growth when cells isolated directly
      from epidermis were employed in study. Some role of DBA-reactive glycoligand
      expressions in a suprabasal movement of differentiated basal cells can be
      hypothesized.

PMID- 12500944
TI  - The integrin beta1 subunit cytoplasmic tail forms oligomers: a potential role in
      beta1 integrin clustering.
AB  - Integrins are alpha/beta heterodimeric cell surface receptors devoid of enzymatic
      activity. Signal transduction therefore requires the association of cytosolic and
      cytoskeletal proteins with the integrin subunit intracellular regions. This
      association is initiated upon ligand binding to the integrin receptor and
      includes clustering of the integrins and recruitment of focal adhesion-associated
      proteins. Whether integrin clustering is solely dependent on ligand binding to
      the integrin extracellular parts or involves also interactions between the
      intracellular tails of integrins is so far unknown. To investigate intracellular
      events in integrin clustering, we have used peptides corresponding to the
      integrin beta1 cytoplasmic region. Loading of cells with the peptides results in
      a decreased cell adhesion and in an inhibition of cell spreading in agreement
      with the previously reported dominant negative effect of the beta1 integrin
      cytoplasmic tail on integrin clustering. Direct protein-protein interaction
      studies by surface plasmon resonance demonstrate that integrin beta1 cytoplasmic
      peptides self-associate in contrast to integrin beta3 cytoplasmic tails. Size
      exclusion chromatography and SDS-PAGE analysis of the peptides further show that
      the integrin beta1 cytoplasmic parts form oligomers and that they assume alpha
      helical conformation to the extent of about 13% and that this fraction is
      increased upon aggregation. Thus self-association of the integrin beta1 subunit
      cytoplasmic regions may be central to beta1 integrin clustering.

PMID- 12500945
TI  - Expression of slow skeletal myosin heavy chain 2 gene in Purkinje fiber cells in
      chick heart.
AB  - In avian, there are three slow skeletal myosin heavy chain (MHC) isoforms, slow
      skeletal MHC 1, 2, and 3. While slow skeletal MHC 3 has been characterized, slow
      skeletal MHC 1 and 2 are not yet fully studied. To determine the complete
      sequence of slow skeletal MHC 2, we isolated six overlapping cDNA clones, each
      encoding a portion of chick slow skeletal MHC 2, using the reverse transcription
      polymerase chain reaction (RT-PCR). The entire slow skeletal MHC 2 cDNA consisted
      of 5927 nucleotides including a 104 bp 3'-untranslated region and encoded 1941
      amino acids. Using one of the cDNA clones, we made a probe for in situ
      hybridization. We also used immunohistochemistry to localize slow skeletal MHC 2
      in skeletal and cardiac tissues. These studies showed that in addition to its
      expected expression in the adult chicken slow skeletal muscle, slow skeletal MHC
      2 was expressed in the subendocardial cluster of cells and around the blood
      vessels within the ventricle of late embryos and adults. This isoform was not
      expressed in the myocardium throughout the life of the chicken. Based on
      morphological criteria as well as rich desmin expression, we concluded that the
      subendocardial cluster of cells were Purkinje cells. Although the physiological
      significance of the slow skeletal MHC expression remains elusive at this time,
      this MHC isoform may be used as a specific marker for Purkinje cells.

PMID- 12500946
TI  - Treatment of the rat hepatic stellate cell line, PAV-1, by retinol and palmitic
      acid leads to a convenient model to study retinoids metabolism.
AB  - The main site of vitamin A storage in the liver is the hepatic stellate cells
      (HSC). Involvement of HSC in vitamin A metabolism has mainly been studied using
      primary culture, which represents the most physiological model but technically
      suffers several drawbacks (yield, low reproducibility, etc.). To circumvent these
      problems, we have previously established and characterised an immortalised rat
      HSC line named PAV-1. This study aimed to investigate in PAV-1 and in primary HSC
      (i) the incorporation of retinol and its esterification, (ii) the cellular
      retinol-binding protein (CRBP) content, (iii) the acid retinyl ester hydrolase
      activity (aREH), (iv) the thermal susceptibility and (v) the lipid composition of
      the membranes, which may play a crucial role in retinol transport across cellular
      membrane. In routine conditions of culture, the rate of retinol esterification in
      PAV-1 was low (5.2%) compared to that obtained with primary HSC (69.9%). Retinol
      pre-treatment doubled this esterification rate (10.7%) and the CRBP content in
      PAV-1. The co-incubation with retinol and palmitic acid enabled PAV-1 to esterify
      retinol with a rate close to that of primary HSC (66.2% vs. 69.9%) and with
      similar retinyl ester profiles. aREH activity was higher in primary HSC than in
      PAV-1. Thermal susceptibility and phospholipid composition of membranes in PAV-1
      treated cells were similar to those of primary HSC. In conclusion, our study
      shows that PAV-1 cells treated with retinol and palmitic acid is a sound and
      convenient model for studying vitamin A mobilisation, a fundamental physiological
      event occurring in HSC.

PMID- 12500947
TI  - Covariations of adolescent weight-control, health-risk and health-promoting
      behaviors.
AB  - OBJECTIVES: To assess the prevalence of dieting and investigate clusters of risk
      behaviors among adolescents. METHODS: Data were secured from a random sample of
      adolescents (4,636) and analyzed using bivariate methods and logistic regression.
      RESULTS: From the survey sample, 19.2% adolescents were classified as extreme,
      43.2% as moderate dieters, 37.2% as nondieters. Extreme dieters were more likely
      to use alcohol, cigarettes, and/or marijuana and to attempt suicide and less
      likely to practice vigorous exercise. Moderate dieters were less likely to use
      cigarettes, marijuana and more likely to engage in vigorous exercise, with
      differences across gender-race categories. CONCLUSIONS: Results have relevance
      for developing multicomponent programs for adolescents.

PMID- 12500948
TI  - The use of the theory of planned behavior to explore beliefs about sugar
      restriction.
AB  - OBJECTIVES: To identify beliefs underlying attitudes, subjective norms and
      perceived behavioral control regarding sugar restriction using the theory of
      planned behavior, TPB. METHODS: A survey of 981 students was conducted in Dar es
      Salaam, Tanzania. RESULTS: The TPB predicted behavioral intention, with R2 =
      0.25. Analysis of variance showed consistent differences between intenders
      (strong intentions) and nonintenders (weak intentions) with regard to beliefs of
      immediate sensory concerns and psychological control factors. CONCLUSIONS:
      Support was provided for the TPB constructs to predict intended sugar
      restriction. Beliefs distinguishing intenders from nonintenders represent targets
      for interventions aimed at maintaining a low-level sugar intake among students in
      Tanzania.

PMID- 12500949
TI  - Tobacco coverage in popular magazines: 1996-1999.
AB  - OBJECTIVE: To determine the extent of coverage of tobacco topics, as compared to
      coverage of health and nonhealth topics, in "general interest" and "health"
      magazines. METHODS: Lead articles and fillers published from 1996 through 1999 in
      9 widely circulated magazines were studied. RESULTS: Less than 1% of all articles
      and fillers on health topics focused on tobacco topics. A smaller proportion of
      tobacco articles and fillers, as compared to other health topics, was published
      in health magazines than in general interest magazines. CONCLUSION: Tobacco is
      covered less, compared to other health topics, especially in health magazines,
      than its importance warrants as a threat to health.

PMID- 12500950
TI  - Trend analysis of cigarette smoking by Indiana adolescents, 1991-2000.
AB  - OBJECTIVES: To examine the feasibility of using a composite index of smoking
      behaviors to analyze adolescent smoking. METHODS: A secondary analysis of data
      from 10 annual surveys (1991-2000), from 566,467 Indiana students in grades 6
      through 12. A composite index was calculated, and differences between index
      scores were analyzed using 1-way ANOVA, Tukey's post hoc tests, and 2-way moving
      averages. RESULTS: Index scores increased before 1997 and decreased after 1976,
      with greater change among 7th through 10th graders. CONCLUSIONS: The 2-way moving
      average comparison of a composite index, used with prevalence-based trend
      analyses, provides a more complete picture of changes in adolescent cigarette
      smoking.

PMID- 12500951
TI  - Development of assessment tools to measure organizational support for employee
      health.
AB  - OBJECTIVE: To develop systems that measure and effect organizational support for
      employee health. METHODS: Multiple studies and developmental projects were
      reviewed that show the process of instrument development, metric quality testing,
      utilization within intervention studies, and prediction modeling efforts.
      RESULTS: Demographic patterns indicate high support levels and relationships of
      subsections to various employee health risks. Successes with the initial version
      have given rise to 2 additional evaluation tools. CONCLUSIONS: The availability
      of these systems illustrates how ecological models can be practically applied.
      Such efforts contribute to the paradigm shift in worksite health promotion that
      focuses on the organization as the target of intervention.

PMID- 12500952
TI  - Pregnancy desire among disadvantaged African American adolescent females.
AB  - OBJECTIVE: To examine the prevalence and correlates of wanting to become pregnant
      among a sample of 462 sexually active nonpregnant African American adolescent
      females. METHODS: Multivariate logistic regression was used to calculate adjusted
      odds ratios, their 95% confidence intervals, and respective P values. RESULTS:
      Significant correlates with pregnancy desire included having a male partner who
      desired pregnancy, having a boyfriend at least 5 years older, having low self
      esteem, perceiving greater perceived barriers to condom use, and perceiving low
      family support. CONCLUSIONS: Pregnancy prevention programs designed for
      economically disadvantaged African American adolescent females should address
      these correlates of their pregnancy desire.

PMID- 12500953
TI  - Exploring family factors and sexual behaviors in a group of Black and Hispanic
      adolescent males.
AB  - OBJECTIVE: To explore family factors that influence sexual behaviors among a
      group of Black and Hispanic adolescent males. METHODS: One hundred seventy-eight
      subjects were selected from a convenience sample of 431 adolescents who
      participated in a 1996 Youth Survey conducted in San Bernardino County,
      California. RESULTS: Having a sibling who was a teen parent was significantly
      associated with engaging in sexual intercourse among Hispanics. Among Blacks,
      having a father who was a teen dad was significantly associated with sexual
      intercourse. CONCLUSIONS: Findings showed relationships between family
      characteristics and sexual attitudes and behaviors among participants.

PMID- 12500954
TI  - Osteoporosis coverage in selected women's magazines and newspapers, 1998-2001.
AB  - OBJECTIVE: To evaluate the accountability of osteoporosis information available
      in selected mass-circulating women's magazines (n=8) and a sample of newspapers
      (n=2). METHODS: Osteoporosis articles (n=132) were assessed for sources of
      information used, incidence/prevalence statistics, risks factors, and prevention
      measures. RESULTS: Expert sources were highlighted in the majority of articles,
      whereas incidence/ prevalence statistics were described in less than half of the
      articles. Risk factors and prevention measures were outlined in most articles;
      however, much of the information presented was ambiguous and incomplete.
      CONCLUSIONS: It appears that the reporting of osteoporosis in women's magazines
      and newspapers is not entirely balanced; thus, future coverage should provide
      greater detail when reporting risks and preventive measures.

PMID- 12500955
TI  - Availability of cigarettes as a risk factor for trial smoking in adolescents.
AB  - OBJECTIVES: To examine associations between cigarette availability measures with
      trial (ie, first) use of cigarettes. METHODS: At Time 1 and one year later (Time
      2), 478 adolescents completed smoking surveys. Trial smoking at Time 2 was
      predicted from Time 1 availability variables (prospective prediction), as well as
      Time 2 availability variables (cross-sectional prediction). RESULTS: Offers from
      friends/classmates were a significant cross-sectional predictor. In prospective
      analyses, greater perceptions of ease of obtaining cigarettes from parents and
      greater frequency of offers from an adult were related to trial smoking.
      CONCLUSIONS: Adult influences, including parental factors, may predispose a young
      adolescent to smoke.

PMID- 12500956
TI  - A student-centered approach to degree program design: case study.

PMID- 12500957
TI  - The racial genetics paradox in biomedical research and public health.

PMID- 12500958
TI  - What is a "health disparity"?

PMID- 12500959
TI  - Why is providing dental care to people with mental retardation and other
      developmental disabilities such a low priority?

PMID- 12500960
TI  - Research and dissemination needs for ergonomics in agriculture.
AB  - In 1998, the National Institute for Occupational Safety and Health convened a
      conference of researchers interested in the ergonomics of agricultural workers.
      Participants included 20 representatives from universities, state governments,
      private agricultural and insurance companies, migrant worker organizations,
      agricultural industry organizations, and the Agricultural Extension Service. The
      attendees divided into three groups and brainstormed about research ideas and
      dissemination methods related to ergonomics for farm workers. The groups
      separately reported that interventions, cost-benefit analyses, and cultural
      belief systems were the main topics that needed to be researched to reduce
      physical risk factors for musculoskeletal disorders. The participants also
      presented ideas for disseminating information to farm owners and workers.

PMID- 12500961
TI  - Lead-based paint health risk assessment in dependent children living in military
      housing.
AB  - OBJECTIVE: In children, lead can cause serious permanent damage as a
      neurotoxicant. The objectives of the study were to evaluate potential exposure to
      lead-based paint in family housing units at a typical U.S. military installation
      and determine blood lead (PbB) levels in children ages 6 years or younger
      residing in these housing units. METHODS: The authors conducted a risk assessment
      of 1,723 housing units and occupants at Fort Devens in Massachusetts. Data from
      the military dependent cohort was compared to estimates for the U.S. national
      population as reported from Phase 1 of the Third National Health and Nutrition
      Examination Survey (NHANES III). RESULTS: A total of 1992 individuals (1,009
      males and 983 females) were screened for PbB, stratified into age groups, and
      separated into racial/ethnic categories. Four (0.3%) dust samples and 59 (11.6%)
      internal and 298 (77.8%) external paint chip samples contained hazardous levels
      of lead. The geometric mean PbB concentration for people ages 1 year and older
      reported by NHANES III was 2.8 micro g/dL, compared with 1.5 microg/dL for the
      military installation cohort (p<0.0001). PbB levels were higher for males than
      for females and higher for blacks than whites 6 years of age and older. Hispanics
      had lower PbB concentrations for all age groups except for those ages 1-2.9
      years. Prevalence of PbB levels >10 microg/dL for all age groups was 1.6% in the
      military cohort, compared with 4.5% for the general population. For ages 1-2.9
      years, no blacks or Hispanics and 0.6% of whites had PbB levels >10 micro g/dL,
      compared with 21.6% of blacks, 10.1% of Hispanics, and 8.5% of whites for the
      general population. For ages 3-5.99 years, 0.15% of blacks, 0% of Hispanics, and
      0.3% of whites had PbB levels > or = 10 microg/dL, compared with 20.0% of blacks,
      6.8% of Hispanics, and 3.7% of whites for the general population. CONCLUSION:
      Lead exposure for occupants of on-post military housing is much less than for
      those residing in the civilian sector.

PMID- 12500962
TI  - Improving breastfeeding knowledge, attitudes, and practices of WIC clinic staff.
AB  - OBJECTIVE: This study was conducted to assess the impact of a breastfeeding
      promotion clinic environment project implemented by the state of Mississippi on
      breastfeeding knowledge, attitudes, and practices of WIC clinic staff. METHODS:
      Thirteen pairs of matched intervention and comparison WIC clinics participated in
      the study. Clinical and administrative staff completed pre-test and post-test
      self-administered questionnaires in 1998 and 1999. RESULTS: A total of 397 staff
      members provided pre-test data, and 277 staff members provided post-test data.
      Before project implementation, the intervention and comparison groups were
      similar overall. The majority of staff had positive attitudes/beliefs about
      breastfeeding, but gaps in knowledge and practices were noted. Post-test data
      showed that the project improved knowledge, attitudes/beliefs, and
      confidence/practice of intervention clinic staff. CONCLUSIONS: Clinic environment
      projects, which combine physical improvements and staff training, are effective
      in promoting support for breastfeeding among public health clinic staff. Similar
      interventions may contribute to the overall effectiveness of breastfeeding
      promotion programs.

PMID- 12500963
TI  - Releasing pre-adoption birth records: a survey of Oregon adoptees.
AB  - OBJECTIVE: In June 2000, Oregon implemented a citizen-initiated ballot measure
      that grants adult adoptees access to their birth records, which contain their
      birth parents' identifying information. Because other states are considering
      similar policy changes, the authors explored whether Oregon's new law is meeting
      the information needs of adoptees. METHODS: Birth records were abstracted for a
      9% (221/2,529) random sample of adoptees who obtained their records from June 20,
      2000, to July 20, 2000, to describe the population and the information they
      obtained. Telephone interviews documented their motivations, expectations, and
      whether they considered the birth record useful. RESULTS: The mean age of the
      adoptees was 41 years, 64% were female, and 97% were white. Virtually all
      received information about their birth mother; however, only one-third received
      information about their birth father. Of the 221 sampled, 123 (59%) participated
      in the telephone survey, 12 were ineligible, 84 could not be reached, and 2
      refused. The most common motivations for requesting records were to find birth
      parents (29%) and to obtain medical information (29%). Twenty-nine percent
      received less information than they expected, with many expecting, but not
      receiving, birth father information. Thirty-three (47%) of the 70 adoptees who
      tried to find their birth mother were successful. The records were considered
      "very" useful by 52% of respondents, "somewhat" or "a little" useful by 42%, and
      "not at all" useful by 6%. CONCLUSIONS: The results indicate that many adoptees
      received less information than they expected, and many did not meet their goals
      of finding birth parents or obtaining medical information. Nonetheless, the
      majority considered their birth records useful and important.

PMID- 12500964
TI  - Releasing pre-adoption birth records: the impact of Oregon's experience on its
      vital records department.
AB  - OBJECTIVE: In November 1998, Oregon voters passed Ballot Measure 58, which
      allowed Oregon adoptees > or = 21 years of age access to their original birth
      records, which are sealed at adoption. The objective of this study was to
      evaluate the impact of the measure on the Oregon Health Division (since renamed
      Oregon Health Services) by assessing procedures used and resources needed after
      implementation of Measure 58. METHODS: Vital records employees were interviewed
      about processing, storage, and archive retrieval procedures for pre-adoption
      birth records before, during, and after the implementation of Measure 58 and the
      effect on their usual workload. Personnel time, space, and fiscal resources used
      to process requests for pre-adoption records were also calculated. RESULTS: The
      Oregon Health Division began to receive requests from adoptees immediately
      following the passage of Measure 58 in November 1998, but due to legal
      challenges, they could not be processed until May 31, 2000. From June 2, 2000,
      through October 20, 2000, 12 staff members and two supervisors issued more than
      4,700 pre-adoption birth records while also processing their normal workload,
      which averages more than 135,400 vital record orders annually. Due to the need
      for retrieval from archives, requests for pre-adoption birth records were
      estimated to take 75 hours to process vs. 2-3 minutes for standard requests. Each
      batch of approximately 75 pre-adoption birth records required approximately 12.5
      person-hours from vital records staff and 3-4 person-hours from archive
      personnel; in addition, supervisors spent time responding to incomplete orders,
      informing the public and the media, and responding to concerns of adoptees, birth
      parents, and adoptive parents. Fewer than 1% of requests went unfilled.
      CONCLUSIONS: Implementation of Measure 58 utilized substantial resources of the
      Oregon Health Division. States contemplating similar legislation should consider
      increasing personnel and resources, preparing for intense public and media
      interest, and reorganizing the storage of adoptees' original birth records so
      they are easily retrieved.

PMID- 12500965
TI  - WHO atlas maps global tobacco epidemic.

PMID- 12500967
TI  - Public health degrees--not just for graduate students.

PMID- 12500968
TI  - A double life: academic physician and androgen physiologist.
AB  - My work in physiology was designed to investigate the process of androgen action
      within target cells and to use this information to provide insight into the
      clinical disorders of androgen action. The discovery that the circulating male
      androgen testosterone is 5alpha-reduced to a more potent hormone,
      dihydrotestosterone, in target tissues and that dihydrotestosterone and
      testosterone work by binding to the same androgen receptor protein has provided
      insight into the inherited syndromes of androgen resistance that impair the
      formation of the male urogenital tract during embryogenesis and into the role of
      continued dihydrotestosterone formation in the pathogenesis of prostatic
      hyperplasia in dogs and men.

PMID- 12500969
TI  - Cell biology of acid secretion by the parietal cell.
AB  - Acid secretion by the gastric parietal cell is regulated by paracrine, endocrine,
      and neural pathways. The physiological stimuli include histamine, acetylcholine,
      and gastrin via their receptors located on the basolateral plasma membranes.
      Stimulation of acid secretion typically involves an initial elevation of
      intracellular calcium and/or cAMP followed by activation of a cAMP-dependent
      protein kinase cascade that triggers the translocation and insertion of the
      proton pump enzyme, H,K-ATPase, into the apical plasma membrane of parietal
      cells. Whereas the H,K-ATPase contains a plasma membrane targeting motif, the
      stimulation-mediated relocation of the H,K-ATPase from the cytoplasmic membrane
      compartment to the apical plasma membrane is mediated by a SNARE protein complex
      and its regulatory proteins. This review summarizes the progress made toward an
      understanding of the cell biology of gastric acid secretion. In particular we
      have reviewed the early signaling events following histaminergic and cholinergic
      activation, the identification of multiple factors participating in the
      trafficking and recycling of the proton pump, and the role of the cytoskeleton in
      supporting the apical pole remodeling, which appears to be necessary for active
      acid secretion by the parietal cell. Emphasis is placed on identifying protein
      factors that serve as effectors for the mechanistic changes associated with
      cellular activation and the secretory response.

PMID- 12500970
TI  - Stress-activated cytokines and the heart: from adaptation to maladaptation.
AB  - The ability of the myocardium to successfully compensate for and adapt to
      environmental stress ultimately determines whether the heart will decompensate
      and fail or maintain preserved function. Despite the importance of the myocardial
      response to environmental stress, very little is known with respect to the
      biochemical mechanisms that are responsible for mediating and integrating the
      stress response in the heart. In the present review we summarize recent
      experimental material suggesting that the cytokines expressed within the
      myocardium in response to environmental injury, namely tumor necrosis factor
      (TNF), interleukin-1 (IL-1), and the interleukin-6 (IL-6) family, play an
      important role in initiating and integrating homeostatic responses. However,
      these stress-activated cytokines all have the potential to produce cardiac
      decompensation when expressed at sufficiently high concentrations. Accordingly,
      the theme to emerge from this review is that the short-term expression of stress
      activated cytokines within the heart may be an adaptive response to stress,
      whereas long-term expression of these molecules may be frankly maladaptive by
      producing cardiac decompensation.

PMID- 12500971
TI  - Structural determinants of the calpain inhibitory activity of calpastatin peptide
      B27-WT.
AB  - Calpastatin is the natural specific inhibitor of calpain. Recent research has
      linked uncontrolled calpain activation to tissue damage after neuronal and
      cardiac ischemias, traumatic spine and brain injuries, as well as Alzheimer's
      disease and cataract formation. An imbalance between the activities of calpain
      and calpastatin is believed to be responsible for the pathological role of
      calpain. An important key to understanding calpain regulation by calpastatin is
      to determine, at the molecular level, how calpastatin interacts with calpain to
      inhibit its enzymatic activity. A 27-residue peptide
      (DPMSSTYIEELGKREVTIPPKYRELLA) derived from subdomain 1B of the repetitive domains
      of calpain, named peptide B27-WT, was previously shown to be a potent inhibitor
      of mu- and m-calpain. In this report, a combination of beta-alanine scanning
      mutagenesis and kinetic measurements was used to probe, in a quantitative,
      systematic, and simultaneous fashion, the relative contribution of the amino acid
      side chain and backbone functionalities to the overall calpain-inhibitory
      activity of B27-WT. The study identified two "hot spots," Leu(11)-Gly(12) and
      Thr(17)-Ile(18)-Pro(19), in B27-WT within which the residues critical for
      inhibitory function are clustered. Mutation of any one of the key residues in
      either of the two hot spots resulted in a dramatic loss of inhibitory activity.
      Furthermore, it was shown that a restricted conformation of the Leu(11)-Gly(12)
      and Thr(17)-Ile(18)-Pro(19) backbones is required for the peptide inhibitory
      function. These results suggest a plausible model in which the two hot spots are
      situated at or near the interface(s) of the calpain-calpastatin complex and act
      in a concerted fashion to inhibit calpain. The information on the specific
      contribution of the amide bond and side chain of each key residue to the
      bioactivity of B27-WT will contribute to a better understanding of the mechanism
      of calpain inhibition and lead to novel and effective therapies based on the
      specific inhibition of dysregulated or overactivated calpain.

PMID- 12500972
TI  - Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and
      angiotensin-converting enzyme.
AB  - Endopeptidase 24.15 (EC; ep24.15), neurolysin (EC; ep24.16), and angiotensin
      converting enzyme (EC; ACE) are metallopeptidases involved in neuropeptide
      metabolism in vertebrates. Using catalytically inactive forms of ep24.15 and
      ep24.16, we have identified new peptide substrates for these enzymes. The
      enzymatic activity of ep24.15 and ep24.16 was inactivated by site-directed
      mutagenesis of amino acid residues within their conserved HEXXH motifs, without
      disturbing their secondary structure or peptide binding ability, as shown by
      circular dichroism and binding assays. Fifteen of the peptides isolated were
      sequenced by electrospray ionization tandem mass spectrometry and shared homology
      with fragments of intracellular proteins such as hemoglobin. Three of these
      peptides (PVNFKFLSH, VVYPWTQRY, and LVVYPWTQRY) were synthesized and shown to
      interact with ep24.15, ep24.16, and ACE, with K(i) values ranging from 1.86 to
      27.76 microm. The hemoglobin alpha-chain fragment PVNFKFLSH, which we have named
      hemopressin, produced dose-dependent hypotension in anesthetized rats, starting
      at 0.001 microg/kg. The hypotensive effect of the peptide was potentiated by
      enalapril only at the lowest peptide dose. These results suggest a role for
      hemopressin as a vasoactive substance in vivo. The identification of these
      putative intracellular substrates for ep24.15 and ep24.16 is an important step
      toward the elucidation of the role of these enzymes within cells.

PMID- 12500973
TI  - Comparison of the heme-free and -bound crystal structures of human heme oxygenase
      1.
AB  - Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin. The crystal
      structure of human HO-1 in complex with heme reveals a novel helical structure
      with conserved glycines in the distal helix, providing flexibility to accommodate
      substrate binding and product release (Schuller, D. J., Wilks, A., Ortiz de
      Montellano, P. R., and Poulos, T. L. (1999) Nat. Struct. Biol. 6, 860-867). To
      structurally understand the HO catalytic pathway in more detail, we have
      determined the crystal structure of human apo-HO-1 at 2.1 A and a higher
      resolution structure of human HO-1 in complex with heme at 1.5 A. Although the
      1.5-A heme.HO-1 model confirms our initial analysis based on the 2.08-A model,
      the higher resolution structure has revealed important new details such as a
      solvent H-bonded network in the active site that may be important for catalysis.
      Because of the absence of the heme, the distal and proximal helices that bracket
      the heme plane in the holo structure move farther apart in the apo structure,
      thus increasing the size of the active-site pocket. Nevertheless, the relative
      positioning and conformation of critical catalytic residues remain unchanged in
      the apo structure compared with the holo structure, but an important solvent H
      bonded network is missing in the apoenzyme. It thus appears that the binding of
      heme and a tightening of the structure around the heme stabilize the solvent H
      bonded network required for proper catalysis.

PMID- 12500974
TI  - Lipoxin A4 stimulates a cytosolic Ca2+ increase in human bronchial epithelium.
AB  - Lipoxins are biologically active eicosanoids possessing anti-inflammatory
      properties. Using a calcium imaging system we investigated the effect of lipoxin
      A(4) (LXA(4)) on intracellular [Ca(2+)] ([Ca(2+)](i)) of human bronchial
      epithelial cell. Exposure of the cells to LXA(4) produced a dose-dependent
      increase in [Ca(2+)](i) followed by a recovery to basal values in primary culture
      and in 16HBE14o(-) cells. The LXA(4)-induced [Ca(2+)](i) increase was completely
      abolished after pre-treatment of the 16HBE14o(-) cells with pertussis toxin (G
      protein inhibitor). The [Ca(2+)](i) response was not affected by the removal of
      external [Ca(2+)] but completely inhibited by thapsigargin (Ca(2+)-ATPase
      inhibitor) treatment. Pre-treatment of the bronchial epithelial cells with either
      MDL hydrochloride (adenylate cyclase inhibitor) or (R(p))-cAMP (cAMP-dependent
      protein kinase inhibitor) inhibited the Ca(2+) response to LXA(4). However, the
      response was not affected by chelerytrine chloride (protein kinase C inhibitor)
      or montelukast (cysteinyl leukotriene receptor antagonist). The LXA(4) receptor
      mRNA was detected, by RT-PCR, in primary culture of human bronchial epithelium
      and in immortalized 16HBE14o(-) cells. The functional consequences of the effect
      of LXA(4) on intracellular [Ca(2+)](i) have been investigated on Cl(-) secretion,
      measured using the short-circuit techniques on 16HBE14o(-) monolayers grown on
      permeable filters. LXA(4) produced a sustained stimulation of the Cl(-) secretion
      by 16HBE14o(-) monolayers, which was inhibited by BAPTA-AM, a chelator of
      intracellular calcium. Taken together our results provided evidence for the
      stimulation of a [Ca(2+)](i) increase by LXA(4) through a mechanism involving its
      specific receptor and protein kinase A activation and resulting in a subsequent
      Ca(2+)-dependent Cl(-) secretion by human airway epithelial cells.

PMID- 12500975
TI  - Efficient reduction of target RNAs by small interfering RNA and RNase H-dependent
      antisense agents. A comparative analysis.
AB  - RNA interference can be considered as an antisense mechanism of action that
      utilizes a double-stranded RNase to promote hydrolysis of the target RNA. We have
      performed a comparative study of optimized antisense oligonucleotides designed to
      work by an RNA interference mechanism to oligonucleotides designed to work by an
      RNase H-dependent mechanism in human cells. The potency, maximal effectiveness,
      duration of action, and sequence specificity of optimized RNase H-dependent
      oligonucleotides and small interfering RNA (siRNA) oligonucleotide duplexes were
      evaluated and found to be comparable. Effects of base mismatches on activity were
      determined to be position-dependent for both siRNA oligonucleotides and RNase H
      dependent oligonucleotides. In addition, we determined that the activity of both
      siRNA oligonucleotides and RNase H-dependent oligonucleotides is affected by the
      secondary structure of the target mRNA. To determine whether positions on target
      RNA identified as being susceptible for RNase H-mediated degradation would be
      coincident with siRNA target sites, we evaluated the effectiveness of siRNAs
      designed to bind the same position on the target mRNA as RNase H-dependent
      oligonucleotides. Examination of 80 siRNA oligonucleotide duplexes designed to
      bind to RNA from four distinct human genes revealed that, in general, activity
      correlated with the activity to RNase H-dependent oligonucleotides designed to
      the same site, although some exceptions were noted. The one major difference
      between the two strategies is that RNase H-dependent oligonucleotides were
      determined to be active when directed against targets in the pre-mRNA, whereas
      siRNAs were not. These results demonstrate that siRNA oligonucleotide- and RNase
      H-dependent antisense strategies are both valid strategies for evaluating
      function of genes in cell-based assays.

PMID- 12500976
TI  - Nuclear factor-kappa B and mitogen-activated protein kinases mediate nitric oxide
      enhanced transcriptional expression of interferon-beta.
AB  - Mitogen-activated protein (MAP) kinase and nuclear factor-kappaB (NF-kappaB)
      activation are critical for initiating the transcriptional expression of
      cytokines, cell adhesion molecules, and other factors in the macrophage immune
      response. Nitric oxide (NO), an endogenous free radical, is a product of
      macrophages that mediates inflammatory and cytotoxic processes in the immune
      system. Here we report the effects of NO on MAP kinase signaling and NF-kappaB
      activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and
      correlate these effects to the induction target genes, including interferon-beta
      (IFN-beta) and IkappaB-alpha. LPS alone induced a rapid phosphorylation of the
      stress-activated MAP kinases: c-Jun N-terminal kinase (JNK) and p38. Simultaneous
      treatment with LPS and the NO donor, diethylamine NONOate (DEA/NO), enhanced and
      prolonged JNK and p38 phosphorylation. Similarly, DEA/NO prolonged the LPS
      induced degradation of the NF-kappaB inhibitory subunit, IkappaB-alpha, despite
      an increase in IkappaB-alpha mRNA levels. Whereas DEA/NO alone was sufficient to
      induce JNK and p38 phosphorylation, it was not sufficient to cause IkappaB-alpha
      degradation. The enhancement of IkappaB-alpha degradation by DEA/NO correlated
      with an increase in the nuclear levels of the p50 and p65 subunits and DNA
      binding activity determined by electrophoretic mobility shift assay. DEA/NO and
      an additional NO donor, MAHMA/NO, are further demonstrated to enhance the
      transcriptional expression of the IFN-beta gene. The results suggest a role for
      NO in enhancing and propagating inflammatory conditions and the immune response.

PMID- 12500977
TI  - Expression of prion protein increases cellular copper binding and antioxidant
      enzyme activities but not copper delivery.
AB  - The N-terminal region of the prion protein PrP(C) contains a series of
      octapeptide repeats. This region has been implicated in the binding of divalent
      metal ions, particularly copper. PrP(C) has been suggested to be involved in
      copper transport and metabolism and in cell defense mechanisms against oxidative
      insult, possibly through the regulation of the intracellular CuZn superoxide
      dismutase activity (CuZn-SOD) or a SOD-like activity of PrP(C) itself. However,
      up to now the link between PrP(C) expression and copper metabolism or SOD
      activity has still to be formally established; particularly because conflicting
      results have been obtained in vivo. In this study, we report a link between
      PrP(C), copper binding, and resistance to oxidative stress. Radioactive copper
      ((64)Cu) was used at a physiological concentration to demonstrate that binding of
      copper to the outer plasma cell membrane is related to the level of PrP(C)
      expression in a cell line expressing a doxycycline-inducible murine PrP(C) gene.
      Cellular PIPLC pretreatment indicated that PrP(C) was not involved in copper
      delivery at physiological concentrations. We also demonstrated that murine PrP(C)
      expression increases several antioxidant enzyme activities and glutathione
      levels. Prion protein may be a stress sensor sensitive to copper and able to
      initiate, following copper binding, a signal transduction process acting on the
      antioxidant systems to improve cell defenses.

PMID- 12500978
TI  - Genomic organization of the mammalian MHC.
AB  - The Human Genome Project transformed the quest of more than 50 years to
      understand the major histocompatibility complex (Mhc). The sequence of the Mhc
      from human and mouse, together with a large amount of sequence and mapping
      information from several other species, allows us to draw general conclusions
      about the organization and origin of this crucial part of the immune system. The
      Mhc is a mosaic of stretches formed by conserved and nonconserved genes.
      Surprisingly, of the approximately 3.6-Mb Mhc, the stretches that encode the
      class I and class II genes, which epitomize the Mhc, are the least conserved
      part, whereas the approximately 1.7-Mb stretches that encode at least 115 other
      genes are highly conserved. We summarize the available data to answer the
      questions (a) What is the Mhc? and (b) How can we define it in a general, not
      species-specific, way? Knowing what is essential and what is incidental helps us
      understand the fundamentals of the Mhc, and defining the species differences
      makes the model organisms more useful.

PMID- 12500979
TI  - Molecular mechanisms regulating Th1 immune responses.
AB  - The T helper lymphocyte is responsible for orchestrating the appropriate immune
      response to a wide variety of pathogens. The recognition of the polarized T
      helper cell subsets Th1 and Th2 has led to an understanding of the role of these
      cells in coordinating a variety of immune responses, both in responses to
      pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms
      that control lineage commitment to the Th1 phenotype. What has recently emerged
      is a rich understanding of the cytokines, receptors, signal transduction
      pathways, and transcription factors involved in Th1 differentiation. Although the
      picture is still incomplete, the basic pathways leading to Th1 differentiation
      can now be understood in in vitro and a number of infection and disease models.

PMID- 12500980
TI  - On natural and artificial vaccinations.
AB  - This review summarizes the general parameters of cell- and antibody-mediated
      immune protection and the basic mechanisms responsible for what we call
      immunological memory. From this basis, the various successes and difficulties of
      vaccines are evaluated with respect to the role of antigen in maintaining
      protective immunity. Based on the fact that in humans during the first 12-48
      months maternal antibodies from milk and serum protect against classical acute
      childhood and other infections, the concept is developed that maternal antibodies
      attenuate most infections of babies and infants and turn them into effective
      vaccines. If this "natural vaccination" under passive protective conditions does
      not occur, acute childhood diseases may be severe, unless infants are actively
      vaccinated with conventional vaccines early enough, i.e., in synchronization with
      the immune system's maturation. Although vaccines are available against the
      classical childhood diseases, they are not available for many seemingly milder
      childhood infections such as gastrointestinal and respiratory infections; these
      may eventually trigger immunopathological diseases. These changing balances
      between humans and infections caused by changes in nursing habits but also in
      hygiene levels may well be involved in changing disease patterns including
      increased frequencies of certain autoimmune and degenerative diseases.

PMID- 12500981
TI  - The biology of IGE and the basis of allergic disease.
AB  - Allergic individuals exposed to minute quantities of allergen experience an
      immediate response. Immediate hypersensitivity reflects the permanent
      sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to
      their high-affinity receptors (FcepsilonRI). A combination of factors contributes
      to such long-lasting sensitization of the mast cells. They include the homing of
      mast cells to mucosal tissues, the local synthesis of IgE, the induction of
      FcepsilonRI expression on mast cells by IgE, the consequent downregulation of
      FcgammaR (through an insufficiency of the common gamma-chains), and the
      exceptionally slow dissociation of IgE from FcepsilonRI. To understand the
      mechanism of the immediate hypersensitivity phenomenon, we need explanations of
      why IgE antibodies are synthesized in preference to IgG in mucosal tissues and
      why the IgE is so tenaciously retained on mast cell-surface receptors. There is
      now compelling evidence that the microenvironment of mucosal tissues of allergic
      disease favors class switching to IgE; and the exceptionally high affinity of IgE
      for FcepsilonRI can now be interpreted in terms of the recently determined
      crystal structures of IgE-FcepsilonRI and IgG-FcgammaR complexes. The rate of
      local IgE synthesis can easily compensate for the rate of the antibody
      dissociation from its receptors on mucosal mast cells. Effective mechanisms
      ensure that allergic reactions are confined to mucosal tissues, thereby
      minimizing the risk of systemic anaphylaxis.

PMID- 12500982
TI  - The rotary motor of bacterial flagella.
AB  - Flagellated bacteria, such as Escherichia coli, swim by rotating thin helical
      filaments, each driven at its base by a reversible rotary motor, powered by an
      ion flux. A motor is about 45 nm in diameter and is assembled from about 20
      different kinds of parts. It develops maximum torque at stall but can spin
      several hundred Hz. Its direction of rotation is controlled by a sensory system
      that enables cells to accumulate in regions deemed more favorable. We know a
      great deal about motor structure, genetics, assembly, and function, but we do not
      really understand how it works. We need more crystal structures. All of this is
      reviewed, but the emphasis is on function.

PMID- 12500983
TI  - Metabolic response to provision of mixed protein-carbohydrate supplementation
      during endurance exercise.
AB  - The interaction of substrates and hormones in response to ingestion of intact
      proteins during endurance exercise is unknown. This study characterized substrate
      and hormone responses to supplementation during endurance exercise. Nine male
      runners participated in 3 trials in which a non-fat (MILK), carbohydrate (CHO),
      or placebo (PLA) drink was consumed during a 2-hour treadmill run at 65% VO2max.
      Circulating levels of insulin, glucagon, epinephrine, norepinephrine, growth
      hormone, testosterone, and cortisol were measured. Plasma substrates included
      glucose, lactate, free fatty acids, and select amino acids. Except for insulin
      and cortisol, hormones increased with exercise. While post-exercise insulin
      concentrations declined similarly in all 3 trials, the glucagon increase was
      greatest following MILK consumption. CHO blunted the post-exercise increase in
      growth hormone compared to levels in MILK. Free fatty acids and plasma amino
      acids also were responsive to nutritional supplementation with both CHO and MILK
      attenuating the rise in free fatty acids compared to the increase observed in
      PLA. Correspondingly, respiratory exchange ratio increased during CHO. Essential
      amino acids increased significantly only after MILK and were either unchanged or
      decreased in CHO. PLA was characterized by a decrease in branched-chain amino
      acid concentrations. Modest nutritional supplementation in this study altered the
      endocrine response as well as substrate availability and utilization following
      and during an endurance run, respectively.

PMID- 12500984
TI  - Prevalence of hypoglycemia following pre-exercise carbohydrate ingestion is not
      accompanied By higher insulin sensitivity.
AB  - Pre-exercise carbohydrate feeding may result in rebound hypoglycemia in some but
      not all athletes. The aim of the present study was to examine whether insulin
      sensitivity in athletes who develop rebound hypoglycemia is higher compared with
      those who do not show rebound hypoglycemia. Twenty trained athletes (VO(2max) of
      61.8 +/- 1.4 ml.kg(-1).min(-1)) performed an exercise trial on a cycle ergometer.
      Forty-five minutes before the start of exercise, subjects consumed 500 ml of a
      beverage containing 75 g of glucose. The exercise trial consisted of 20 min of
      submaximal exercise at 74 +/- 1% VO(2max) immediately followed by a time trial.
      Based upon the plasma glucose nadir reached during submaximal exercise, subjects
      were assigned to a Hypo group (<3.5 mmol/L) and a Non-hypo group (> or =3.5
      mmol/L). An oral glucose tolerance test was performed to obtain an index of
      insulin sensitivity (ISI). The plasma glucose nadir during submaximal exercise
      was significantly lower (p <.01) in the Hypo-group (n = 10) compared with the Non
      hypo group (n = 10) (2.7 +/- 0.1 vs. 4.1 +/- 0.2 mmol/L, respectively). No
      difference was found in ISI between the Hypo and the Non-hypo group (3.7+/-0.4
      vs. 3.8 +/- 0.5, respectively). The present results suggest that insulin
      sensitivity does not play an important role in the occurrence of rebound
      hypoglycemia.

PMID- 12500985
TI  - Food and fluid intake and disturbances in gastrointestinal and mental function
      during an ultramarathon.
AB  - The purpose of this study was to document eating strategies employed by runners
      during a 160-km race, and to identify eating patterns that predispose the runner
      to disturbed mental or gastrointestinal functioning. We monitored intake in 19
      volunteers during the 12 hours pre-race. Intake was determined by interview with
      runners approximately every 12 km throughout the race. The mean finish time was
      24.3 hours, with 4 runners not completing the race. Body mass decreased during
      the race, 75.9 +/- 2.3 kg to 74.4 +/- 2.2 kg (p <.001). Runners ingested 2643
      kcals during the 12 hours prerace (68% carbohydrate) and 3.8 L of fluid. During
      the race 6047 kcal, 18 L of fluid, and 12 g of sodium were consumed.
      Gastrointestinal distress (GI) was experienced by half of the participants, but
      was unrelated to food or fluid intake. Upper GI symptoms were more prevalent than
      lower and occurred mainly after 88 km. Runners with GI distress tended to
      complete fewer training miles (p =.10) and to do shorter training runs (p =.08).
      Half of the volunteers reported mental status changes (MSC), such as confusion or
      dizziness. Runners with MSC had greater intake of total calories, carbohydrate,
      and fluid (p <.05) than runners without MSC. They also completed shorter training
      runs (p =.03). Caloric and moisture intake for all runners far exceeded intakes
      described previously. Although intake did not match energy expenditure, it may
      represent the upper limit for absorption during exercise, and very high food
      and/or fluid intake appears to lead to perturbed mental status.

PMID- 12500986
TI  - Sweat iron and zinc losses during prolonged exercise.
AB  - The purpose of this study was to examine the effects of a 2-hour exercise bout on
      sweat iron and zinc concentrations and losses in males and females. Nine male and
      9 female recreational cyclists exercised at approximately 50% VO(2peak) in a
      temperate environment (Ta = 23 degrees C, RH = 51%). Sweat samples were collected
      for 15 min during each of four 30-min exercise bouts. No significant differences
      were observed between males' and females' sweat iron or zinc concentrations or
      losses. Sweat iron concentrations decreased significantly between 60 and 90 min
      of exercise. Sweating rates increased significantly from 30 to 60 min and
      remained constant during the second hour. Sweat iron losses were significantly
      lower during the second hour (0.042 mg/m2/h) than the first hour of exercise
      (0.060 mg/m2/h). Sweat zinc concentrations also decreased significantly over the
      2-hour exercise bout. Dietary intakes of iron and zinc were not significantly
      correlated to sweat iron and zinc concentrations. Sweat iron and zinc losses
      during 2 hours of exercise represented 3% and 1% of the RDA for iron and 9% and
      8% of the RDA for zinc for men and women, respectively. These results suggest a
      possible iron conservation that prevents excessive iron loss during prolonged
      exercise.

PMID- 12500987
TI  - Caffeine ingestion does not alter performance during a 100-km cycling time-trial
      performance.
AB  - This study analyzed the effect of caffeine ingestion on performance during a
      repeated-measures, 100-km, laboratory cycling time trial that included bouts of 1
      and 4-km high intensity epochs (HIE). Eight highly trained cyclists participated
      in 3 separate trials' placebo ingestion before exercise with a placebo
      carbohydrate solution and placebo tablets during exercise (Pl), or placebo
      ingestion before exercise with a 7% carbohydrate drink and placebo tablets during
      exercise (Cho), or caffeine tablet ingestion before and during exercise with 7%
      carbohydrate (Caf). Placebo (twice) or 6 mg.kg(-1) caffeine was ingested 60 min
      prior to starting 1 of the 3 cycling trials, during which subjects ingested
      either additional placebos or a caffeine maintenance dose of 0.33 mg.kg(-1) every
      15 min to trial completion. The 100-km time trial consisted of five 1-km HIE
      after 10, 32, 52, 72, and 99 km, as well as four 4-km HIE after 20, 40, 60, and
      80 km. Subjects were instructed to complete the time trial and all HIE as fast as
      possible. Plasma (caffeine) was significantly higher during Caf (0.43 +/- 0.56
      and 1.11 +/- 1.78 mM pre vs. post Pl; and 47.32 +/- 12.01 and 72.43 +/- 29.08 mM
      pre vs. post Caf). Average power, HIE time to completion, and 100-km time to
      completion were not different between trials. Mean heart rates during both the 1
      km HIE (184.0 +/- 9.8 Caf; 177.0 +/- 5.8 Pl; 177.4 +/- 8.9 Cho) and 4-km HIE
      (181.7 +/- 5.7 Caf; 174.3 +/- 7.2 Pl; 175.6 +/- 7.6 Cho; p <.05) was higher in
      Caf than in the other groups. No significant differences were found between
      groups for either EMG amplitude (IEMG) or mean power frequency spectrum (MPFS).
      IEMG activity and performance were not different between groups but were both
      higher in the 1-km HIE, indicating the absence of peripheral fatigue and the
      presence of a centrally-regulated pacing strategy that is not altered by caffeine
      ingestion. Caffeine may be without ergogenic benefit during endurance exercise in
      which the athlete begins exercise with a defined, predetermined goal measured as
      speed or distance.

PMID- 12500988
TI  - Effects of long-term creatine supplementation on liver and kidney functions in
      American college football players.
AB  - The purpose of this study was to determine the effect of long-term Cr
      supplementation on blood parameters reflecting liver and kidney function. Twenty
      three members of an NCAA Division II American football team (ages = 19-24 years)
      with at least 2 years of strength training experience were divided into a Cr
      monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously
      ingested creatine, and a control group (n = 13) in which they took no
      supplements. Individuals in the CrM group averaged regular daily consumption of 5
      to 20 g (mean   SD = 13.9   5.8 g) for 0.25 to 5.6 years (2.9   1.8 years).
      Venous blood analysis for serum albumin, alkaline phosphatase, alanine
      aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine
      produced no significant differences between groups. Creatinine clearance was
      estimated from serum creatinine and was not significantly different between
      groups. Within the CrM group, correlations between all blood parameters and
      either daily dosage or duration of supplementation were nonsignificant.
      Therefore, it appears that oral supplementation with CrM has no long-term
      detrimental effects on kidney or liver functions in highly trained college
      athletes in the absence of other nutritional supplements.

PMID- 12500989
TI  - The effect of bovine colostrum supplementation on exercise performance in elite
      field hockey players.
AB  - In a double-blind, randomized, placebo-controlled study, we investigated the
      effect of 8 weeks of supplementation with bovine colostrum (Intact) on body
      composition and exercise performance (5 x 10-m sprint, vertical jump, shuttle-run
      test, and suicide test). Seventeen female and 18 male elite field hockey players,
      including players from the Dutch national team, received either 60 g of colostrum
      or whey protein daily. The 5 x 10-m sprint test performance improved
      significantly (p =.023) more in the colostrum group [0.64 +/- 0.09 s (mean +/-
      SEM)] compared to the whey group (0.33 +/- 0.09 s). The vertical jump performance
      improved more in the colostrum group (2.1 +/- 0.73 cm) compared to the whey group
      (0.32 +/- 0.82 cm). However, this was not statistically significant (p =.119).
      There were also no significant differences in changes in body composition and
      endurance tests between the 2 groups. It is concluded that in elite field hockey
      players, colostrum supplementation improves sprint performance better than whey.
      However, there were no differences with regard to body composition or endurance
      performance.

PMID- 12500990
TI  - Effect of acute and short-term administration of vanadyl sulphate on insulin
      sensitivity in healthy active humans.
AB  - Vanadium compounds have been shown to have insulin-like properties in rats and
      non-insulin-dependent diabetic humans. The purpose of the present study was to
      examine whether the effects of acute and short-term administration of vanadyl
      sulfate (VA) on insulin sensitivity also exist in healthy active individuals.
      Five male and two female participants (age: 24.9 +/- 1.5 years; height: 176.1 +/-
      2.9 cm; body mass: 70.1 +/- 2.9 kg) underwent 3 oral glucose tolerance tests
      (OGTT). The first OGTT was performed to obtain a baseline index of insulin
      sensitivity (ISI). On the night preceding the second OGTT, participants ingested
      100 mg of VS, and the acute effects of VS on ISI were examined. For the next 6
      days, participants were instructed to ingest 50 mg of VS twice daily, and a final
      OGTT was performed on day 7 to determine the short-term effects of VS on ISI. No
      differences were found in fasting plasma glucose and insulin concentrations after
      VS administration. Furthermore, ISI after 1 day and 7 days of VS administration
      was not different compared with baseline ISI (4.8 +/- 0.1 vs. 4.7 +/- 0.1 vs. 4.7
      +/- 0.1, respectively). These results demonstrate that there are no acute and
      short-term effects of VS administration on insulin sensitivity in healthy humans.

PMID- 12500991
TI  - The effect of diet manipulations on aerobic performance.
AB  - The purpose of this study was to examine the metabolic consequences of a moderate
      variation in dietary fat content of male endurance athletes during submaximal
      exercise. Six males (age, 29.8 +/- 11 years; weight, 72.3 +/- 10 kg) with an
      average maximum oxygen uptake (VO(2max)) of 66 +/- 10 ml/kg/min were tested on
      their normal diet and 3 experimental diets. The energy contributions from
      protein, carbohydrates, and fats were 16/59/22 (3% alcohol), 14/53/33, 13/72/15,
      and 16/61/23% for the normal diet (N), fat supplemented diet (F), high
      carbohydrate diet (C), and adjusted normal diet (AN), respectively. The F diet
      was designed to significantly increase fat content compared to the normal diet
      and be easily maintained by the athletes. Caloric content of the F, C, and AN
      diets were adjusted to meet estimated total daily energy expenditure. The
      difference between the N and AN diets is that the AN has been adjusted to meet
      estimated total daily energy expenditure. The diets were randomly assigned after
      substrate utilization testing on the N diet and were consumed for 7 days prior to
      testing. Substrate utilization was recorded at steady state (73 +/- 1.4% of
      VO(2max)) while running on a treadmill for 40 min. There were no significant
      differences in respiratory exchange ratio between any of the dietary
      manipulations. No significant differences were observed for lactate, VO2, or HR
      during submaximal testing on the N, F, C, and AN diets. These data indicate that
      a fat supplemented diet did not affect substrate utilization during 40 min of
      steady-state submaximal exercise when compared to a high carbohydrate diet or the
      participant's normal and adjusted normal diets.

PMID- 12500992
TI  - Feeding ultra-endurance athletes: an interview with Dr. Helen O'Connor and
      Gregory Cox. Interview by Louise M. Burke.

PMID- 12500993
TI  - Tissue temperature transients in resting contra-lateral leg muscle tissue during
      isolated knee extension.
AB  - This study was designed to evaluate the role of non-active tissue in the
      retention and dissipation of heat during and following intense isolated muscle
      activity. Six subjects performed an incremental isotonic test (constant angular
      velocity, increases in force output) on a KIN-COM isokinetic apparatus to
      determine their maximal oxygen consumption during single knee extensions (VO2sp).
      In a subsequent session, a thin wire multi-sensor temperature probe was inserted
      into the left vastus medialis under ultrasound guidance at a specific internal
      marker. The deepest temperature sensor (tip, Tmu10) was located approximately 10
      mm from the femur and deep femoral artery with 2 additional sensors located at 15
      (Tmu25) and 30 (Tmu40) mm from the tip. Implant site was midway between and
      medial to a line joining the anterior superior iliac spine and base of patella.
      Esophageal temperature (Tes) temperature was measured as an index of core
      temperature. Subjects rested in a supine position for 60 min followed by 30 min
      of seated rest in an ambient condition of 22 degree C. Subjects then performed 15
      min of isolated single right knee extensions against a dynamic resistance on a
      KIN COM corresponding to 60% of VO2sp at 60 degree x sec(-1). Exercise was
      followed by 60 min of seated rest. Resting Tes was 37 degree C while Tmu10,
      Tmu25, and Tmu40 were 36.58, 36.55 and 36.45 degree C, respectively. Exercise
      resulted in a Tes increase of 0.31 C above pre-exercise resting. Tmu of the non
      exercising leg increased 0.23, 0.19 and 0.09 degree C for Tmu10, Tmu25, and
      Tmu40, respectively. While Tes decreased to baseline values within approximately
      15 min of end-exercise, Tmu10 reached resting values following approximately 40
      min of recovery. These results suggest that during isolated muscle activity,
      convective heat transfer by the blood to non-active muscle tissue may have a
      significant role in maintaining resting core temperature.

PMID- 12500995
TI  - Physical fitness in young college men and women.
AB  - This study was designed to investigate fitness characteristics of college women
      and men (n = 427 and 423, respectively) aged 17-20 years whose values were
      compared to the data of the 1981 Canada Fitness Survey (CFS). Muscular fitness as
      revealed by the maximal number of arm extensions (push ups) was lower in subjects
      of this study compared to those tested in the 1981 CFS. On the other hand, body
      weight, waist circumference and the sum of five skinfolds were greater in
      subjects of the present study. These differences between the results of this
      study and those of the 1981 CFS were particularly pronounced in the upper
      percentile ranks. The classification of subjects on the basis of the number of
      grades completed during a step test revealed significant differences in
      subcutaneous adiposity between fitness subgroups. Reported participation in
      vigorous physical activities was also predictive of subcutaneous adiposity in men
      but to a lesser extent than the number of grades completed during a step test.
      When the number of grades and exercise participation were combined to detect
      between-group morphological differences, large differences in subcutaneous
      adiposity were observed in both men and women. This suggests that the effect of
      vigorous activity and aerobic fitness on adiposity may be much greater than what
      is generally perceived by health professionals and agencies.

PMID- 12500994
TI  - Effect of fourteen days of acclimatization on athletic performance in tropical
      climate.
AB  - In order to study the acclimatization process over 14 days of exposure to
      tropical climate, 9 triathletes performed 4 outdoor indirect continuous
      multistage tests in both thermoneutral and tropical conditions. The thermoneutral
      test (TN, 14 degree C, 45% rh) was performed before traveling to the tropical
      area (Martinique, FWI). The tropical tests were performed 2, 8, and 14 days after
      arrival (32.9 degree C, 78% rh). During each trial, we measured tympanic
      temperature, sweat rate, body mass loss, heart rate (HR), and performance. The
      results showed that 1). the mean tympanic temperature was greater in T2 (P
      <.001), T8 (P <.01) and T14 (P <.01) than in TN and significantly lower in T14
      than in T2 (P <.05); 2). the mean sweat rate was significantly greater (P <.001)
      in T2, T8 and T14 than in TN and significantly greater (P <.05) in T8 and T14
      than in T2; 3). the body mass loss after trials was significantly greater (P
      <.001) in T2, T8 and T14 than in TN and significantly greater (P <.05) in T8 and
      T14 than in T2; 4). the mean HR and HR at rest were significantly higher (P
      <.005) in T2 than in TN, T8, T14 and the mean HR was significantly lower (P <.05)
      in T14 than in the other trials; and 5). the performance time was significantly
      lower in T2 (P < 0.02), T8 (P < 0.03) and T14 (P < 0.05) than in TN. We concluded
      that 14 days of exposure to tropical climate led to changes in physiological
      parameters but were still insufficient to ensure complete acclimatization in well
      trained athletes. The hot/wet climate induced impairment of physiological
      responses and performance that were still evident on the 14th day.

PMID- 12500996
TI  - Development and validation of a one-mile treadmill walk test to predict peak
      oxygen uptake in healthy adults ages 40 to 79 years.
AB  - The purpose of this investigation was to determine whether the Rockport one-mile
      walk test equation to predict maximal oxygen uptake was valid for application to
      treadmill walking. When the Rockport model was found to be inappropriate, a new
      regression model was developed for predicting peak oxygen uptake (VO2peak) from a
      one-mile treadmill walk. 304 healthy volunteers ages 40 to 79 years (mean age =
      57.6 years, 154 men and 150 women) completed a VO2peak test and a one-mile
      treadmill walk. Stepwise regression was used to build a model for the
      relationship between VO2peak and a variety of predictor variables in a sub-sample
      development group (n = 154). This new model was then applied to a sub-sample
      validation group (n = 150). The new equation produced a correlation of 0.87, SEE
      = 4.7 ml x kg (-1) x min (-1) with a mean residual of 0.96 ml x kg (-1) x min (
      1). The equation for predicting VO2peak developed in this investigation provides
      a means of assessing VO2peak that is easy to administer, allows for careful
      supervision of subjects, and can be completed at a low financial and temporal
      cost.

PMID- 12500997
TI  - Evaluation of the interchangeability of VO2MAX and oxygen uptake efficiency
      slope.
AB  - A reliable submaximal test for assessing cardiorespiratory function would be of
      interest in clinical practice. Baba et al. (1996) proposed the oxygen uptake
      efficiency slope (OUES) derived from the relation between oxygen uptake (VO2 [ml
      x min (-1) x kg (-1)]) and minute ventilation (VE [L x min (-1)]) during
      incremental exercise. We evaluated the validity of OUES by comparing maximal
      oxygen uptake (VO2MAX) predicted from OUES to measured VO2MAX in 50 healthy males
      who performed a maximal treadmill test. They had widely differing physical
      fitness levels (VO2MAX range, 32.7 to 80.2 mlO2 x min(-1) x kg(-1). Predicted
      VO2MAX was not significantly different (p > 0.99) from measured VO2MAX (56.8 7.0
      vs. 56.8 8.8 mlO2 x min 1 kg(-1). The limits of agreement (Bland Altman, 1986)
      were plus or minus 10.5 mlO2 x min(-1) x kg(-1). Although OUES and VO2MAX were
      significantly correlated (r = 0.79), the wide interindividual variations in the
      difference between these two parameters may limit the usefulness of OUES in
      clinical practice.

PMID- 12500998
TI  - Effect of paddling cadence on time to exhaustion and VO2 kinetics at the
      intensity associated with VO2max in elite white-water kayakers.
AB  - The influence of paddling cadence on the time to exhaustion (t.lim) and VO2
      kinetics at the intensity associated with VO2max (IVO2max) was examined in seven
      highly-trained white water kayakers. All subjects were engaged in national or
      international competitions. Subjects took part in three constant-load tests at
      IVO2max, each test performed at a different paddling cadence (50, 60 or 70 cycles
      min(-1). The VO2 kinetics recorded during these constant-load tests at IVO2max
      were fitted with a mono-exponential equation. A significant increase in t.lim (P
      <.05) was observed as the paddling cadence increased from 50 to 70 cycles min(
      1). No effect was found either on values of VO2peak, post-exercise blood lactate
      concentration, or on the time at which VO2peak was attained (TAVO2peak). Our
      results suggest that experienced kayakers may choose a high paddling cadence
      during physiological assessments at IVO2max. Further experiments are needed in
      order to identify the physiological significance of t.lim at IVO2max.

PMID- 12500999
TI  - Passive resistive torque of the plantar flexors following eccentric loading as
      assessed by isokinetic dynamometry.
AB  - Isokinetic dynamometers may provide a useful means of measuring muscle stiffness
      resulting from eccentric exercise because they can measure torque from computer
      controlled passive movements of joints (passive resistive torque; PRT). In this
      study, a Biodex measured increased ankle PRT (52%; p <.001) following heel drop
      exercise in nine young women. Therefore, isokinetic dynamometers can provide a
      means to study group changes as a result of eccentric exercise. Future studies
      are required to determine the reliability of this protocol before it can be
      advocated in studying single cases.

PMID- 12501000
TI  - Effects of conjugated linoleic acid (CLA) on immune responses, body composition
      and stearoyl-CoA desaturase.
AB  - Conjugated linoleic acid (CLA) has shown a wide range of biologically beneficial
      effects; reduction of incidence and severity of animal carcinogenesis, reduction
      of the adverse effects of immune stimulation, reduction of severity of
      atherosclerosis, growth promotion in young rats, and modulation of stearoyl-CoA
      desaturase (SCD). One of the most interesting aspects of CLA is its ability to
      reduce body fat while enhancing lean body mass which is associated with the trans
      10,cis-12 isomer of CLA. The effects of CLA are unique characteristics that have
      not been observed with other polyunsaturated fatty acids. In this review, we will
      focus on the effects of CLA on immune responses, body compositional changes and
      stearoyl-CoA desaturase.

PMID- 12501001
TI  - Effects of prohormone supplementation in humans: a review.
AB  - Despite a relative dearth of information on their effects, supplementation with
      prohormones has become a popular practice. Unlike synthetic anabolic-androgenic
      steroids, many of these over-the-counter androgens are produced endogenously by
      adrenal, gonadal and peripheral steroidogenic pathways as part of the normal
      sexual and reproductive hormonal milieu. It has been contended that peripheral
      enzymatic conversion of these prohormones to testosterone or nortestosterone (via
      ingestion of androstenedione/androstenediol or 19-nor
      androstenedione/androstenediol, respectively) might lead to anabolic and/or
      ergogenic effects. Existing data suggest that acute oral ingestion of >or=200 mg
      androstenedione or androstenediol modestly and transiently increases serum
      testosterone concentrations in men; however, this is accompanied by greater
      increases in circulating estrogen(s). At doses < 300 mg/d, oral supplementation
      for as long as 12-weeks with androstenedione or androstenediol has no effect on
      body composition or physical performance and decreases high-density lipoprotein
      cholesterol. Similarly, oral supplementation with norandrostenedione and
      norandrostenediol for up to eight weeks has no effect on body composition or
      physical performance. In light of these data, new products have been developed
      that use alternative modes of prohormone administration (sublingual/transbuccal
      and cyclodextrin-complexation). Future studies should critically examine the
      effects of these approaches. However, within the framework of the research
      reviewed, over-the-counter oral prohormone supplementation is ineffective at
      increasing muscle mass or athletic performance. As a result of the potential
      health concerns that have been raised, the risk to benefit ratio of using these
      substances orally seems unfavorable.

PMID- 12501002
TI  - Role of leucine in protein metabolism during exercise and recovery.
AB  - Exercise produces changes in protein and amino acid metabolism. These changes
      include degradation of the branched-chain amino acids, production of alanine and
      glutamine, and changes in protein turnover. One of the amino acid most affected
      by exercise is the branched-chain amino acid leucine. Recently, there has been an
      increased understanding of the role of leucine in metabolic regulations and
      remarkable new findings about the role of leucine in intracellular signaling.
      Leucine appears to exert a synergistic role with insulin as a regulatory factor
      in the insulin/ phosphatidylinositol-3 kinase (PI3-K) signal cascade. Insulin
      serves to activate the signal pathway, while leucine is essential to enhance or
      amplify the signal for protein synthesis at the level of peptide initiation.
      Studies feeding amino acids or leucine soon after exercise suggest that post
      exercise consumption of amino acids stimulates recovery of muscle protein
      synthesis via translation regulations. This review focuses on the unique roles of
      leucine in amino acid metabolism in skeletal muscle during and after exercise.

PMID- 12501003
TI  - Dietary creatine supplementation and exercise performance: why inconsistent
      results?
AB  - Over the past few years there has been considerable interest in both the use of
      creatine (Cr) supplementation by athletes and the documentation of its effects by
      scientists. Some believe that this nitrogen-containing compound found in meat and
      fish has a performance-enhancing capability as important for brief intense
      exercise efforts as dietary carbohydrate is for activities where glycogen
      supplies limit performance. The mechanisms thought to be responsible for any
      ergogenic effect of acute (few d) Cr supplementation include: increased stores of
      muscle phosphocreatine (PCr), faster regeneration of PCr during exercise
      recovery, enhanced adenosine triphosphate (ATP) production from glycolysis
      secondary to increased hydrogen ion buffering, and/or possible shortened post
      contraction muscle relaxation time. With chronic (wk mo) supplementation when
      combined with strength training, Cr may alter muscle protein metabolism directly
      (via decreasing protein breakdown or increasing synthesis) and/or indirectly as a
      result of a greater training load made possible by its acute ergogenic effects on
      strength and power. Cr supplementation is not banned by the International Olympic
      Committee and, with the exception of a small increase in body mass (approximately
      1 kg) over the initial 36 d, does not appear to have any adverse side effects, at
      least with short-term use. Few scientific data are available for more prolonged
      use (mo or y) but considering the large numbers of athletes using Cr over the
      past 6+ y and the absence of reported problems, it may be that the often
      discussed somewhat nebulous long term adverse effects are presently being
      overestimated. Intakes of 285-300 mg Cr/kg body mass 1 over 36 d or 3050 mg/kg
      body mass 1 over approximately 4 wk are sufficient to produce benefits (muscle
      mass and high intensity power gains); however, not all study results are
      consistent. The focus of this review is to outline some possible explanations for
      the inconsistent observations reported in the literature. Clearly, if proven to
      be consistent the benefits of Cr supplementation could extend far beyond the
      athletic arena to include individuals who experience muscle weakness for a
      variety of other reasons (e.g., age/disuse, muscle disease, exposure to
      microgravity, etc).

PMID- 12501004
TI  - Canadian population trends in leisure-time physical activity levels, 1981-1998.
AB  - Age, sex, geographic and temporal trends in leisure-time physical activity levels
      were examined using data from five national surveys conducted between 1981 and
      1998. Physical activity energy expenditure (AEE) was higher among men compared to
      women, and in younger versus older adults. AEE increased from Eastern to Western
      Canada, with a significant temporal trend of increasing AEE. The prevalence of
      physical inactivity (expending <12.6 kJ x kg(-1) x day(-1) has decreased;
      however, it remains high (women: 77%; men: 74%). The high prevalence of physical
      inactivity emphasizes the importance of population-level physical activity
      surveillance and interventions.

PMID- 12501005
TI  - Protective effect of ebselen, a seleno-organic compound, against the progression
      of acute gastric mucosal lesions induced by compound 48/80, a mast cell
      degranulator, in rats.
AB  - The protective effect of ebselen, which possesses glutathione peroxidase-like
      activity and antioxidative and anti-inflammatory properties, against the
      progression of acute gastric mucosal lesions was examined in rats with a single
      intraperitoneal injection of compound 48/80 (0.75 mg/kg). Ebselen (50, 100 or 200
      mg/kg) was orally administered 0.5 h after compound 48/80 treatment, at which
      time gastric mucosal lesions appeared. Post-administered ebselen suppressed
      gastric mucosal lesion progression at 3 h after compound 48/80 treatment dose
      dependently, although no dose of ebselen affected the decreased gastric mucosal
      blood flow and increased serum serotonin and histamine concentrations found at 3
      h after the treatment. A decrease in Se-glutathione peroxidase activity and
      increases in myeloperoxidase and xanthine oxidase activities and the
      concentration of thiobarbituric acid reactive substances were found in gastric
      mucosal tissues at 0.5 h after compound 48/80 treatment, and these changes were
      further enhanced at 3 h. Post-administered ebselen attenuated all these changes
      found at 3 h after compound 48/80 treatment dose-dependently. The present results
      indicate that ebselen exerts a protective effect against the progression of
      compound 48/80-induced acute gastric mucosal lesions in rats, and they suggest
      that this protective effect of ebselen could be due to its glutathione peroxidase
      like activity and its antioxidative and anti-inflammatory properties.

PMID- 12501006
TI  - Relationship between 24-hour rhythm in antiviral effect of interferon-beta and
      interferon-alpha/beta receptor expression in mice.
AB  - The influence of interferon-beta (IFN-beta) dosing time on antiviral activity was
      investigated in ICR male mice under light-dark cycle conditions (lights on at
      07:00, off at 19:00) with food and water available ad libitum. There was a
      significant dosing time-dependent change in 2',5'-oligoadenylate synthetase
      (2',5'-OAS) activities, as an index of antiviral activity, in liver at 12 h after
      IFN-beta (15 MIU/kg, i.v.) injection. IFN-beta-induced 2',5'-OAS activity was
      more potent after the drug injection during the late dark phase. The higher
      antiviral effect of IFN-beta was observed when the interferon-alpha/beta receptor
      (IFNAR) expression in the liver increased, and the lower effect was observed when
      its expression decreased. IFN-beta-induced fever was more serious after IFN-beta
      injection from the late dark phase to the early light phase. A significant dosing
      time-dependent change was demonstrated for plasma IFN-beta concentrations, which
      showed a higher level during the light phase and a lower level during the dark
      phase. The dosing time-dependent change of plasma IFN-beta concentrations was not
      associated with that of the antiviral effect or fever induced by IFN-beta. These
      results suggest that selecting the most suitable dosing time of IFN-beta,
      associated with the 24-h rhythm of IFNAR expression in the liver, may be
      important to increase effectively the antiviral activity of the drug in
      experimental and clinical situations.

PMID- 12501007
TI  - Effects of mosapride citrate, a 5-HT4 receptor agonist, on colonic motility in
      conscious guinea pigs.
AB  - It is known that 5-HT(4) receptors in the colon of guinea pigs show a
      distribution similar to that in humans. Thus, we examined the effects of
      mosapride citrate (mosapride) and cisapride, two 5-HT(4)-receptor agonists, on
      colonic motility in conscious guinea pigs implanted with force transducers.
      Mosapride and cisapride administered intragastrically at doses of 3 - 30 mg/kg
      significantly enhanced the colonic motility. The enhancing effect of mosapride
      was antagonized by atropine or GR113808, a 5-HT(4)-receptor antagonist, but not
      by methysergide, a 5-HT(1)- and 5-HT(2)-receptor antagonist; ondansetron, a 5
      HT(3)-receptor antagonist; or CP-99994, a tachykinin NK(1)-receptor antagonist.
      In vitro receptor autoradiography showed that mosapride and cisapride inhibit the
      specific binding of [(125)I]-SB207710, a selective radioligand of 5-HT(4)
      receptors, in the colon of guinea pigs. These results suggest that mosapride
      enhances colonic motility through the 5-HT(4)-receptor activation in guinea pigs
      and may be useful for treating constipation in patients with colonic motility
      dysfunction.

PMID- 12501008
TI  - Hypoxia enhances beta-amyloid-induced apoptosis in rat cultured hippocampal
      neurons.
AB  - We investigated the effect of hypoxia on beta-amyloid (Abeta)-induced apoptosis
      in rat cultured hippocampal neurons. Abeta (25 microM for 48 h) decreased the
      number of neuronal cells and increased the number of TUNEL-positive cells.
      Hypoxia (6 h) also decreased the number of neuronal cells, but did not increase
      the number of TUNEL-positive cells. Moreover, combined treatment with both Abeta
      and hypoxia (Abeta/hypoxia) significantly enhanced the decrease in the number of
      neuronal cells and the increase in the number of TUNEL-positive cells. Z-Asp
      CH(2)-DCB, an inhibitor of interleukin-1beta-converting enzyme (ICE), or 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (non-NMDA)
      receptor antagonist, decreased the number of TUNEL-positive cells with
      Abeta/hypoxia. These findings suggest that ischemia or hypoxia is an important
      factor that facilitates the symptoms of Alzheimer's disease and that non-NMDA
      receptors are involved in the induction of apoptosis in patients suffering from
      both cerebrovascular disease and Alzheimer's disease.

PMID- 12501009
TI  - Possible involvement of suppression of Th2 differentiation in the anti-allergic
      effect of Sho-seiryu-to in mice.
AB  - The clinical effectiveness of the Kampo medicine Sho-seiryu-to (SST) has recently
      been demonstrated in a double-blind randomized study of allergic asthma and
      rhinitis. We investigated the effect of SST on a type 1 allergic model in mice.
      Ovalbumin (OVA)-induced sneezing and the total and OVA-specific IgE levels were
      significantly suppressed with SST at 1.0 g/kg, but that of OVA-specific IgG(2a)
      was not. In the splenocytes isolated from SST-administered mice, OVA-induced
      interleukin (IL)-4 production decreased while interferon (IFN)-gamma production
      was not. The co-culture experiments using purified CD4(+)T cells and antigen
      presenting cells (APCs) suggested that SST influenced both cell types. Flow
      cytometric analysis showed that SST suppressed the number of IL-4 producing
      CD4(+)T cells but not the number of IFN-gamma producing CD4(+)T cells. The
      CD86(+) major histocompatibility complex class II(+) (MHC II)(+) cells and
      CD28(+)CD4(+)T cells were decreased by SST treatment, while CD80(+)MHC II(+)
      cells, CD40(+)MHC II(+) cells and CD154(+)CD4(+)T cells showed no change. These
      data suggested that SST may suppress IL-4 production in CD4(+)T cells via
      influencing CD28-CD86 interaction. In addition to the previously reported
      inhibitory activity on histamine release, suppression of Th2 differentiation at
      the stage of APC-CD4(+)T cell interaction may be involved in the anti-allergic
      effects of SST.

PMID- 12501010
TI  - Cerivastatin, a HMG-CoA reductase inhibitor, reduces plasminogen activator
      inhibitor-1 (PAI-1) expression in endothelial cells by down-regulation of
      cellular signaling and the inhibition of PAI-1 promoter activity.
AB  - Statins, which competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase activity and reduce mevalonate synthesis, are believed to exert a
      plethora of pleiotropic effects. In this report, molecular mechanisms of the
      inhibitory effect on plasminogen activator inhibitor type 1 (PAI-1) expression
      produced by cerivastatin (CRV), the most active compound in this class, were
      studied using monocultures of human endothelial cell line (EA.hy 926). CRV
      similar to another statin, lovastatin (LOV), significantly inhibited PAI-1
      expression and its release from endothelial cells, nonstimulated and stimulated
      with TNF-alpha. The inhibitory effect of CRV could be detected at the level of
      PAI-1 promoter in EA.hy 926 cells transfected with plasmid p800 LUC containing
      PAI-1 promoter fragment (+71 to -800), as well as at the level of PAI-1 mRNA. The
      PAI-1 promoter activity was markedly suppressed in the nonstimulated cells and
      almost completely inhibited in TNF-alpha-stimulated cells. In addition, CRV at
      low doses (IC(50) of 4 - 6 microM) significantly inhibited mitogen-activated
      protein kinases (MAPKs) phosphorylation. The majority of inhibitory effects
      occurred at significantly lower concentrations for CRV compared to LOV. The
      mechanism by which CRV inhibits PAI-1 expression appears to be directly
      associated with geranylgeranylation of some cell proteins, since the inhibitory
      effect on PAI-1 expression can be reversed by geranylgeranyl-pyrophosphate but
      not by farnesyl-pyrophosphate.

PMID- 12501011
TI  - Ginkgo biloba extract markedly induces pentoxyresorufin O-dealkylase activity in
      rats.
AB  - We examined the effect of Ginkgo biloba extract (GBE) on hepatic drug
      metabolizing enzymes, particularly cytochrome P450 (CYP), in rats. Rats were fed
      a GBE-containing diet or received GBE by intragastric gavage. The concentration
      of CYP and activity of various CYP enzymes in the liver were increased in a dose-
      and time-dependent manner. Significant increases in the concentration and
      activities of CYP enzymes were detected on day 1 of feeding of a 0.5% GBE diet
      and after administration of 10 mg GBE/kg body weight for 5 days by intragastric
      gavage. Among the CYP enzymes, the activity of pentoxyresorufin O-dealkylase
      (PROD), a CYP2B enzyme, was especially markedly increased. The induction of CYP2B
      enzyme by GBE was confirmed by Western blot analysis. Addition of GBE to a CYP
      assay system in vitro caused concentration-dependent inhibition of various CYP
      enzyme activities. The inhibition was more marked for the microsomal enzymes from
      GBE-treated rats than for those from control rats and more marked against PROD
      activity among the CYP enzymes tested. When the inhibition of various CYP enzymes
      activities by GBE in vitro was compared, no marked difference was observed
      between rat and human hepatic microsomal enzymes. These results indicate that
      excess intake of GBE induces CYP enzymes, particularly PROD, and may modify the
      efficacy of drugs taken simultaneously.

PMID- 12501012
TI  - In vivo evidence for a lack of central effect of ebastine, an antihistaminic
      agent, in rats: a microdialysis study.
AB  - The effects of ebastine and its active metabolite carebastine on brain dopamine
      uptake and the accessibility to brain were compared with those for a classical
      antihistaminic agent chlorpheniramine by using the microdialysis technique. Both
      carebastine and chlorpheniramine potently inhibited brain [(3)H]dopamine uptake
      and increased the extracellular concentration of dopamine in the striatum after
      local perfusion via microdialysis probes, although systemic injection of ebastine
      but not chlorpheniramine did not change the dopamine level. These findings
      suggest that neither ebastine nor carebastine affects central dopamine metabolism
      because of a limited access to brain, in spite of having a potent inhibitory
      action on neuronal dopamine uptake.

PMID- 12501013
TI  - A polysaccharide, extract from Grifola frondosa, induces Th-1 dominant responses
      in carcinoma-bearing BALB/c mice.
AB  - A polysaccharide, designated as the D-fraction, extracted from maitake (Grifola
      frondosa), was reported to have anti-tumor effects by activating macrophages and
      T cells in C3H/HeN mice in which a Th-1 dominant response was established. In
      this study using BALB/c mice in which a Th-2 response is genetically dominant, D
      fraction reduced the expression of Th-2 cytokine interleukin (IL)-4 but markedly
      increased the expression of Th-1 cytokine interferon (IFN)-gamma in CD4(+) T
      cells and also increased IL-12p70 production as well as IFN-gamma production by
      antigen-presenting cells (APCs), suggesting that D-fraction promotes the
      differentiation into Th-1 cells of CD4(+) T cells through enhancement of IL-12p70
      production by APCs.

PMID- 12501014
TI  - Role of renin-angiotensin system and nuclear factor-kappaB in the obstructed
      kidney of rats with unilateral ureteral obstruction.
AB  - The present study was conducted to elucidate the role of oxidative stress and
      nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin
      receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in
      rats elicited tubulo-interstitial fibrosis with concomitant macrophage
      infiltration and increased expression of monocyte chemoattractant protein-1.
      These changes were accompanied by an induction of renal cortical lipid
      peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan,
      and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these
      changes and to a similar extent. These results suggest that the beneficial
      effects of angiotensin blockade are mediated by the inhibition of oxidative
      stress and subsequent NF-kappaB activation in obstructive nephropathy.

PMID- 12501015
TI  - Bone and joint sports injuries: the role of bone scintigraphy.

PMID- 12501016
TI  - Localization and diagnosis of septic endoprosthesis infection by using 99mTc
      HMPAO labelled leucocytes.
AB  - The aim of this study was to evaluate, retrospectively, the diagnostic value of
      Tc hexamethylpropylene amine oxime (99mTc-HMPAO) labelled autologous leucocytes
      for the preferred septic localizations of the infection of the endoprosthesis. We
      retrospectively reviewed 67 patients with implanted endoprostheses. Diagnosis was
      found in 42/67 patients. In 25/67 patients we were able to negate an acute
      pathological process of infection of the endoprosthesis. Our patients were
      divided into three groups according to the type of endoprosthesis (hip joint,
      knee joint, shoulder joint). The localizations of the endoprosthesis disorders
      are shown. The preferred localizations of the acute infection of the hip
      endoprosthesis are the regio intertrochanterica and the middle part of the shaft
      of the prosthesis. The preferred localization of the acute infection of the knee
      endoprosthesis is the proximal shaft of the tibia. The preferred localization of
      the acute infection of the shoulder endoprosthesis is the distal end of the
      prosthesis in the proximal humerus. It is hoped that the knowledge of these
      preferred localizations of infection of endoprosthesis will help patients and
      doctors in diagnosis and treatment in the future.

PMID- 12501017
TI  - The value of bone marrow scintigraphy using 99mTc monoclonal antigranulocyte
      antibodies in complement to bone scintigraphy in detecting bone metastases from
      primary breast cancer.
AB  - This prospective study evaluates bone marrow scintigraphy (BMS) in detecting bone
      metastases from primary breast cancer when performed in complement to
      conventional bone scan (BS). Sixty women predominantly with low-stage disease
      underwent BS followed by BMS within 1-35 days using BW250/183 antigranulocyte
      antibodies. A receiver operating characteristic (ROC) analysis was performed to
      compare BS to BS+BMS on a patient-by-patient basis using a 'gold standard'
      composed of subsequent computed tomography, magnetic resonance imaging, X-ray or
      BS examinations and at least a 12 month follow-up. Metastases were present in
      eight out of 60 patients (13%). Specificity was improved by BS+BMS compared to BS
      alone (90%, 65%) as well as positive predictive value (62%, 27%), accuracy (87%,
      72%), positive (10.4, 2.4) and negative (0.20, 0.00) likelihood ratios.
      Sensitivity (100%, 88%) and negative predictive value (100%, 97%) were similar
      for BMS+BS and BS alone. As a result of BMS, clinical management was modified in
      15 patients (25%). In conclusion, BMS supplements BS by improving specificity,
      positive predictive value and accuracy in detecting breast cancer bone
      metastases. The ROC curves show improved specificity for BS+BMS at the same
      sensitivity compared to BS alone. Consequently, BMS may be useful in low-stage
      subjects with positive or equivocal BS for metastases.

PMID- 12501018
TI  - Staging of recurrent and advanced lung cancer with 18F-FDG PET in a coincidence
      technique (hybrid PET).
AB  - The aim of this study was to evaluate [18F]fluorodeoxyglucose ( F-FDG) imaging of
      recurrent or inoperable lung cancer using a hybrid positron emission tomography
      (PET) device of the third generation. Examinations were compared with the results
      of conventional staging. Thirty-six patients suffering from recurrent or
      primarily inoperable lung cancer (29 men, seven women; age 64.8+/-12.0 years)
      were examined using hybrid PET (Marconi Axis gamma-PET ) 60 min after injection
      of 370 MBq F-FDG. The data obtained were reconstructed iteratively. All patients
      received a computed tomography (CT) scan using either the spiral or multislice
      technique. All lesions suspicious for primary or recurrent tumour were verified
      by biopsy; mediastinal lymph nodes were considered as malignant, when positive
      histology or a small axis diameter of greater than 1 cm measured with CT in
      addition to progression of clinical course was found. Distant metastases were
      diagnosed by CT and bone scintigraphy. Using hybrid PET all lesions showed a
      focally elevated glucose metabolism. Lymph node involvement of the ipsilateral
      peribronchial and hilar station (N1) was identified in 24/26 cases (92%), in
      26/29 cases (90%) of ipsilateral central manifestation (N2) and in 11/13 (85%)
      cases of central contralateral or supraclavicular lymphatic infestation (N3).
      Pulmonary spread in hybrid PET was found in 4/8 cases (50%), whereas mainly lung
      metastases with a diameter of 1.5 cm and smaller were missed. Pleural involvement
      diagnosed by CT was verified in 4/5 patients. All four patients with bony
      metastases in conventional staging also presented with positive findings in
      hybrid PET (8/9 lesions). Concordance with conventional staging was found in
      28/36 of patients (78%). In 4/36 patients (11%) unknown sites of tumour were
      detected leading to therapeutic consequences in three patients after radiological
      confirmation. Hybrid PET would have led to an understaging in four cases (11%),
      resulting theoretically in inefficient treatment in two patients. Hybrid PET for
      F-FDG imaging in the staging of recurrent or primarily inoperable lung cancer
      supplied equal (78%) or more information (11%) compared to conventional staging
      procedures. Using the information of hybrid PET alone, 11% of the patients would
      have been understaged. We conclude that hybrid PET has the potential for use as
      an additional staging tool in this subgroup of patients, providing supplementary
      information compared to conventional staging modalities.

PMID- 12501019
TI  - Comparison of 99mTc-MIBI uptakes on planar images with those in excised rats
      organs.
AB  - The precision with which images reflect tracer uptake in the myocardium has been
      studied. Additionally, the degree to which Tc methoxyisobutylisonitrile (99mTc
      MIBI) in the liver gave the effect to a myocardial image has been examined. After
      administering Tc-MIBI to normal male rats, we compared the myocardial uptakes
      obtained using a gamma camera with the actual uptakes in the excised organs.
      Twenty-nine rats were used. Following imaging, the anterior view at 5, 10, 15,
      30, 45, 60, 90 and 120 min after administration of the tracer, uptakes in the
      heart, lung, liver and blood were estimated with a well-type scintillation
      counter (WC) and represented as the percentage of the injected dose per gram of
      tissue (%ID/g). The regions of interest (ROIs) were placed on planar images (PI)
      and the uptake in each organ was estimated as the percentage of the injected dose
      per pixel (%ID/pixel). The ratios of PI-to-WC and heart-to-organ were also
      evaluated. Cardiac uptake with WC was maximum (1.581%+/-1.893%) at 10 min post
      injection. On the other hand, that with PI was maximum (1.493%+/-0.598%) at 45
      min post-injection, but there were significant differences between both
      measurements (PI/WC ratio: about 1.0 time). Pulmonary uptake with WC was the
      maximum at 5 min (0.808%+/-0.015%) post-injection, and decreased gradually. PI
      measurement showed the maximum value at 45 min (0.760%+/-0.012%). Hepatic uptake
      with WC was the maximum at 30 min (0.594%+/-0.254%). On the other hand, PI
      measurement showed the same pattern with WC, but these values were higher value
      than WC as the whole. PI measurement showed higher uptakes in each organ than WC
      measurement. It was concluded that uptakes or the heart-to-organ ratio obtained
      clinically with PI might not represent a value that is always accurate.

PMID- 12501020
TI  - Relationship between myocardial counts and patient weight: adjusting the injected
      activity in myocardial perfusion scans.
AB  - It is generally accepted that the quality of myocardial images deteriorates with
      increasing patient weight. This is attributed to a reduction of counts detected
      from the myocardium. In this paper we have looked at the count reduction in obese
      patients and suggest a workable algorithm to increase the injected activity to
      compensate for this loss of count. In this prospective study, 64 consecutive
      patients with normal myocardial images were selected to include a weight range of
      50-120 kg. The height, weight and gender of patients were noted. Each patient had
      two studies (total of 128 studies), one at rest and one following stress with
      adenosine and 20-40 W bicycle exercise. Total myocardial counts were calculated
      from the back-projected views. The total myocardial counts per MBq of the
      injected activity were calculated. There was no significant difference in the
      injected activity and the size of the heart (pixel length of heart) between
      stress and rest, or gender of the patient. The normalized myocardial counts were
      not different between men and women, but the counts were slightly, although not
      significantly, higher ( P=NS) with adenosine and exercise (mean of 243 x 10(3)
      counts) compared to rest images (229 x 10(3) counts). There was a significant
      progressive loss of counts in patients with increasing weight, body mass index or
      body surface area ( P<0.001). There was no significant difference in the changes
      in counts with weight between male and female, or rest and stress studies. The
      combined data from all the studies were used to calculate the correlation
      coefficient and the slope of the line for reduction of cardiac counts with a
      patient's weight, body mass index, and body surface area. The best correlation
      was with patient weight ( r=0.58, P<0.001). This was used to calculate the
      increase in injection activity with increasing weight to maintain the same
      average counts as achieved in a 70 kg patient with a 400 MBq injection. We
      suggest that the injection activity should increase from 100% for a 70 kg patient
      to 140% for 110 kg, 200% for 140 kg, and 250% for a 150 kg patient.

PMID- 12501021
TI  - Radioimmunometric assay of natriuretic peptide type-B (BNP) in heart failure.
AB  - The aim of this study was to assess the value of the radioimmunometric
      determination of natriuretic peptide type-B (brain natriuretic peptide, BNP) in
      the diagnosis and prognosis of heart failure, and to study the association
      between BNP and the clinical, analytical and echocardiographic variables
      associated with the evolution of heart failure. The study group included 169
      patients (74 women and 95 men; mean, 66 years) with heart failure of different
      causes, admitted consecutively to our hospital. BNP levels were measured with a
      radioimmunometric assay (Shionora BNP Cis ) after day 3 of admission. Patients
      were also studied by echocardiography. A significant association between the
      cause of heart failure and the BNP concentration was found (patients with
      ischaemic disease had the highest BNP values). Systolic function was worse in
      patients with ischaemic disease or dilated cardiomyopathy. High BNP values were
      also associated with advanced functional class and male sex. Plasma creatinine
      correlated positively with plasma BNP. However, we found no significant
      association with the other clinical variables evaluated. Of the echocardiographic
      variables analysed, BNP correlated positively with the ventricular diameter and
      pulmonary artery systolic pressure, and inversely with the shortening fraction;
      patients with severely impaired systolic function had the highest BNP values. It
      can be concluded that BNP levels (by radioimmunometric assay) are increased in
      patients with heart failure, and increase in relation to left ventricular
      dysfunction and the severity of heart failure. The strong independent association
      of plasma BNP with the left ventricular ejection fraction, its stability and the
      low cost of measurement suggest that plasma BNP assay could become a routine
      test. BNP assay could be included as an important factor in clinical and
      therapeutic decision making, as it complements the information provided by other
      variables used in the diagnosis of heart failure.

PMID- 12501022
TI  - Effect of calcium antagonist on cerebral blood flow and oxygen metabolism in
      patients with hypertension and chronic major cerebral artery occlusion: a
      positron emission tomography study.
AB  - To evaluate the effect of a calcium antagonist, nilvadipine, on cerebral blood
      flow and oxygen metabolism, we prospectively examined five ischaemic stroke
      patients, with both hypertension and chronic major cerebral artery occlusion,
      using positron emission tomography. The blood pressure showed a significant
      decrease after 3 months of nilvadipine treatment, the cerebral blood flow in the
      affected regions showed a significant increase and the oxygen extraction fraction
      showed a significant decrease. We conclude that nilvadipine is a safe and
      effective anti-hypertensive agent for patients with both hypertension and chronic
      major cerebral artery occlusion.

PMID- 12501023
TI  - 99mTc-TRODAT-1 SPECT in healthy and 6-OHDA lesioned parkinsonian monkeys:
      comparison with 18F-FDOPA PET.
AB  - Parkinson's disease (PD) is a degeneration of the nigrostriatal dopaminergic
      pathway, leading to a selective loss of dopamine in the striatum. 99mTc-TRODAT-1
      is a recently developed radiotracer that selectively binds to the dopamine
      transporters, which are significant because loss of these transporters
      corresponds with a loss of dopaminergic neurons. The present investigation
      compared 99mTc-TRODAT-1 single photon emission computed tomography (SPECT) with
      18F-FDOPA positron emission tomography (PET) in the evaluation of PD using a
      primate model. Three monkeys, including one 6-hydroxydopamine lesioned PD model
      and two controls, were examined by both 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET.
      For the PD monkey, expression of parkinsonian behaviour and 18F-FDOPA PET were
      used to evaluate the severity of the lesion. 99Tc-TRODAT-1 was prepared from a
      lyophilized kit. After intravenous injection of the radiotracer, SPECT was
      acquired over 4 h using a dual-head camera equipped with ultra-high resolution
      fan-beam collimators. Both uptake measurement and visual assessment were
      performed. Data were compared with motor behaviour and PET imaging. The striatal
      uptake in both healthy and PD monkeys increased continuously during the study,
      although the gradient of increase was less prominent in the diseased monkey. The
      increased uptake in the controls appeared to become blunt around 4 h after
      injection. A profound decrease of 99Tc-TRODAT-1 uptake was found in the striatum
      of the PD monkey compared with the controls (0.91 vs 2.16). In the PD monkey, the
      decrease of striatal uptake contralateral to the more affected side of the body
      was more prominent compared to the ipsilateral side (0.77 vs 1.06). In addition,
      greater loss occurred in the contralateral side of the putamen (0.54 vs 1.04).
      Changes of uptake ratios in the striatum and its subnuclei of the PD monkey were
      significantly correlated with those measured from PET. The loss of striatal
      uptake appeared greater in SPECT than the corresponding PET with both visual and
      uptake analyses. In conclusion, our data in a limited series of cases indicate
      that 99Tc-TRODAT-1 with a conventional nuclear medicine camera system may provide
      a suitable tool in evaluating parkinsonism in a primate model.

PMID- 12501024
TI  - Double-phase parathyroid 99mTc-Sestamibi scintigraphy in chronic haemodialysis
      patients: correlation with biochemical markers of parathyroid function.
AB  - 99mTc-Sestamibi identifies the presence of hyperfunctioning autonomous
      parathyroid glands in patients with secondary hyperparathyroidism (SHP). The
      objectives of this study were: (i) to evaluate the interdependence between
      biochemical markers of SHP and 99mTc-Sestamibi uptake; and (ii) to determine
      whether 99mTc-Sestamibi uptake could be efficiently predicted by any combination
      of the former variables. Double-phase parathyroid 99mTc-Sestamibi uptake and
      total serum calcium, phosphorus, intact parathormone, 25-OH vitamin D and
      1,25(OH) vitamin D determinations were performed simultaneously in 74 patients
      (36 female, 38 male) with SHP. Planar images of the neck and upper thorax were
      obtained in anterior view, 15 min (early phase) and 120 min (delayed phase) after
      the injection of 740 MBq of 99mTc-Sestamibi. In each patient, a final
      parathyroid/thyroid (P/T) activity index was obtained by adding the results of
      the P/T index of all parathyroid lesions. There was a significant correlation
      between intact parathormone levels and delayed 99mTc-Sestamibi uptake ( r=0.656;
      P<0.01). Of all the variables, intact parathormone was the only significant
      predictor of delayed 99Tc-Sestamibi uptake ( r=0.487; P<0.001). Calcium,
      phosphorus, vitamin D metabolites, age, gender, time spent on haemodialysis and
      cause of chronic renal failure displayed no significant correlation with 99mTc
      Sestamibi uptake. It can be concluded that 99mTc-Sestamibi uptake is a potential
      predictor of parathyroid function in SHP patients. Hence, 99mTc-Sestamibi
      scintigraphy could be useful to assess parathyroid function and in the clinical
      follow-up of these patients.

PMID- 12501025
TI  - A survey of the role of the UK physicist in nuclear medicine: a report of a joint
      working group of the British Institute of Radiology, British Nuclear Medicine
      Society, and the Institute of Physics and Engineering in Medicine.
AB  - Guidelines for the provision of physics support to nuclear medicine were
      published in 1999 by a joint working group of the British Institute of Radiology,
      the British Nuclear Medicine Society, and the Institute of Physics and
      Engineering in Medicine. Following publication of the guidelines, a survey was
      conducted by the working group to gather data on the actual level of physicist
      support in UK hospitals of different types and on the activities undertaken by
      physicists. The data were collected in the 12 months following the publication of
      guidelines and cover different hospital models and seven UK regions. The results
      provide evidence that many of the smaller units - small teaching hospitals and,
      particularly, small district general hospitals - have insufficient physics
      support. Although, on average, there is good agreement between the guidelines and
      the survey data for medium and large district general hospitals, there is wide
      variation in the level of physics provision between hospitals delivering
      apparently similar services. This emphasizes the need for national guidelines,
      against which institutions may be bench-marked and which may be used as a
      recommendation for the staffing levels necessary to ensure services are delivered
      safely and standards are not compromised. The complexity and variety of workload
      is an important factor in determining the level of physics support. As services
      develop, it is vital that this aspect is recognized to ensure that appropriate
      resources are available for the required physics input, even if any new service
      represents only a modest clinical throughput in terms of patient numbers.

PMID- 12501026
TI  - Database deconvolution.
AB  - A new deconvolution technique is described. It regards the Rutland-Patlak plot as
      the integral of the retention function, and performs deconvolution by creating
      and then differentiating the Rutland-Patlak plot. The reasoning behind this
      approach is that in producing the Rutland-Patlak plot, both the content function
      and the integral of the input function are divided by the input function (i.e.
      the blood curve), and that this has the effect of producing data equivalent to
      that which would be produced if the input function did not vary (i.e. if there
      were a constant blood level of tracer). The concept was tested against data
      created by modelling techniques. It was able to reproduce retention functions
      with a variety of different shapes that were used to produce the artificial
      renogram data. The new deconvolution method is sufficiently simple to be used in
      either a database or a spreadsheet and does not require any special program units
      to be written. It does not appear to make any assumptions about the data nor the
      shape of the retention function, and does not appear to be vulnerable to the
      oscillating errors that sometimes occur in iterative deconvolution.

PMID- 12501027
TI  - Creative solutions in times of shortage.

PMID- 12501028
TI  - A curriculum in emergency medicine for Europe.

PMID- 12501029
TI  - Are hypertonic hyperoncotic solutions safe for prehospital small-volume
      resuscitation? Results of a prospective observational study.
AB  - RATIONALE: This prospective observational study was designed to shed light on the
      routine use of a hypertonic hyperoncotic solution for prehospital small-volume
      resuscitation in trauma patients. Effects on homeostasis and haemodynamics as
      well as safety were evaluated. METHODS: One hundred patients with haemorrhagic
      shock were given hypertonic hyperoncotic solution (6% hydroxyethyl starch plus
      7.5% sodium chloride) by bolus infusion (approximately 4 ml/kg bodyweight). Blood
      was taken before small-volume resuscitation and after the patients' arrival in
      the emergency room and serum electrolytes, haemoglobin, haematocrit, colloid
      osmotic pressure and white cell counts were determined. Haemodynamic variables
      were evaluated before small-volume resuscitation, just before transport and on
      arrival. RESULTS: Serum sodium and serum chloride increased at best moderately
      between baseline and arrival (7 and 12 mmol/l, medians; P<0.001) with peak
      increases of 25 mmol/l for serum sodium and 23 mmol/l for serum chloride. Serum
      potassium and white cell counts showed no more than minor changes. Haematocrit,
      haemoglobin and colloid osmotic pressure dropped (7%, 2.3 g/dl and 3.8 mmHg,
      respectively, medians; P<0.001). On arrival oxygen saturation and systolic and
      diastolic blood pressure had increased (5%, 30 and 20 mmHg, respectively),
      whereas heart rate had dropped by 15 b.p.m. (medians; P<0.001). Five patients
      developed heat sensations, restlessness, voiding urge, poor taste and vomiting,
      which may have been hypertonic hyperoncotic solution-related. CONCLUSION: Per
      protocol bolus infusions of hypertonic hyperoncotic solution containing
      hydroxyethyl starch do not compromise homeostasis clinically and are rarely
      associated with clinically manifest side-effects. The treatment regimens used
      (including small-volume resuscitation) provide early and effective haemodynamic
      control.

PMID- 12501030
TI  - Epidemiology, treatment and outcome of acidotic, acute, cardiogenic pulmonary
      oedema presenting to an emergency department.
AB  - In this retrospective cohort study, 172 patients presenting to two accident and
      emergency departments in the UK, with acute, cardiogenic pulmonary oedema were
      identified. The median age of the patients was 77 years and there was an equal
      sex distribution. The commonest therapy given in the acute treatment of this
      condition was frusemide, and less than 70% of the cohort received nitrates. Only
      73.8% survived to hospital discharge, and only 50.6% were alive one year later.
      Using logistic regression analysis, the use of nitrate medication in the
      emergency department was associated with improved survival to hospital discharge
      (odds ratio 3.04; 95% confidence interval 1.15-8.01). It is recommended that
      nitrates are given to all patients presenting to emergency departments with acute
      cardiogenic pulmonary oedema whose blood pressure will allow the use of such
      therapy.

PMID- 12501031
TI  - The impact of television fiction on public expectations of survival following
      inhospital cardiopulmonary resuscitation by medical professionals.
AB  - RATIONALE: Research has shown that the public overestimates the survival chances
      of patients after cardiopulmonary resuscitation. Other studies have suggested
      that demonstrably exaggerated survival rates in medical television fiction might
      affect these estimates. Such studies were mostly conducted in the United States,
      dealt with cardiopulmonary resuscitation in general, and asked respondents to
      indicate their source of medical information, an unreliable survey technique.
      OBJECTIVE: To examine whether public perceptions of survival after inhospital
      cardiopulmonary resuscitation by physicians and nurses is related to the
      consumption of medical drama, without relying on respondents' self-reports of
      what influences them. To examine whether training in basic cardiopulmonary
      resuscitation techniques mediates this relationship. METHODS: A random sample of
      820 third and fifth year secondary school students completed a questionnaire in
      which they indicated their consumption of medical television fiction, their
      practical knowledge of cardiopulmonary resuscitation techniques, and their
      estimates of the survival rate after inhospital cardiopulmonary resuscitation.
      RESULTS: A relationship was found between the consumption of medical television
      drama and higher estimates of cardiopulmonary resuscitation survival. Practical
      knowledge of cardiopulmonary resuscitation also resulted in increased estimated
      survival rates. An interaction effect of drama and practical knowledge was found.
      Respondents with practical knowledge were less affected by television.
      CONCLUSIONS: The consumption of medical television drama is related to
      overestimating survival chances after inhospital resuscitation by physicians and
      nurses following cardiopulmonary arrest. A practical knowledge of basic
      cardiopulmonary resuscitation techniques moderates but does not eliminate the
      television effect.

PMID- 12501032
TI  - The role of abdominal computed tomography scanning in patients with non-traumatic
      abdominal symptoms.
AB  - OBJECTIVES: To describe the non-traumatic clinical settings in which abdominal
      computed tomography (CT) is used and to determine its diagnostic utility.
      METHODS: A retrospective descriptive study of consecutive non-traumatic adult
      patients who underwent abdominal CT in a university hospital emergency department
      (ED). Radiology reports and patient charts were reviewed. The indication for each
      CT was determined by two reviewers. Indications were described as specific (e.g.
      "rule-out" appendicitis) or non-specific (e.g. abdominal pain). CT results were
      classified as positive, negative (normal or no new information) or indeterminate
      (technical limitations). For those with specific indications, positive results
      were further subdivided into supportive (of the clinical suspicion) or non
      supportive (abnormal but suggesting an alternative diagnosis). The clinical
      course and results of subsequent diagnostic procedures were used to confirm CT
      results for admitted patients. Incidental CT findings were recorded. RESULTS: 177
      patients were entered; mean age was 58 years; 48% were men. The most frequent
      indications ("rule-outs") were aortic disorders (23%), abscess (16%), and
      diverticulitis (14%). In patients with specific indications (n=160), 44% of the
      CT results supported the indication, 13% suggested an alternative diagnosis (non
      supportive), 41% were negative, and 3% were indeterminate. In admitted patients
      (n=129), CT findings were contradicted in 6%. CONCLUSIONS: Adult ED patients
      undergo abdominal CT for a variety of non-traumatic indications. Findings in less
      than half support the pre-test clinical suspicion and an alternative previously
      unsuspected diagnosis is suggested in 13%. Follow-up is inconsistent with CT
      results in a small but significant number of cases.

PMID- 12501033
TI  - Neurosurgical emergencies and missing neurosurgical intensive care unit capacity:
      is "operate-and-return" a sound policy?
AB  - Available neurosurgical intensive care beds are rare and are often regarded as a
      precondition for accepting remote neurosurgical emergencies for operative
      treatment. From a medical and ethical point of view, the practice of rejecting
      acute patients as a result of a shortage of intensive care unit beds is
      questionable, because the primary need is fast treatment, and postoperative
      intensive care is secondary. We performed a retrospective analysis of outcome of
      36 patients, who returned straight from our operating room to the intensive care
      unit of the referring hospital because no domestic neurosurgical intensive care
      unit beds were available (group 1). For the two largest cohorts, acute subdural
      haematoma ( =12) and primary intracerebral haemorrhage ( =15), outcome was
      compared by matched pair analysis with control patients kept in-house
      postoperatively (group 2). The mortality rate was higher in group 1 compared with
      group 2 (acute subdural haematoma 67 versus 58%; intracerebral haemorrhage 47
      versus 40%). Despite this tendency, we regard "operate-and-return" treatment as a
      sound and practicable alternative to offer to hospitals trying to refer patients
      with neurosurgical emergencies. It is to be preferred to denying treatment,
      because this results in a delay or cancellation of treatment, with the associated
      negative effects on outcome. However, postoperative neurosurgical intensive care
      unit treatment has to be considered the optimum goal, and there needs to be a
      continuous demand to authorities to increase the number of neurosurgical
      intensive care unit beds.

PMID- 12501034
TI  - Effervescent paracetamol poisoning: a case report.
AB  - Severe poisoning with effervescent paracetamol tablets has never been described
      in the literature. Indeed, the effervescent formulation contains high amounts of
      sodium and bicarbonate, both responsible for important emetic properties in the
      case of massive ingestion. Moreover, dissolving more than 6-8 tablets in the same
      glass appears to be difficult. We report a well-documented case of a patient with
      potentially hepatotoxic serum levels after the ingestion of 16 g effervescent
      paracetamol, apparently without vomiting. We show that the difficulties of a
      massive oral intake may be overcome by a slow intake. Nevertheless, this case
      report does not modify the important assertion that effervescent paracetamol use
      could limit the risk of life-threatening intoxication by a single massive acute
      overdose.

PMID- 12501035
TI  - Six clinical cases of Mandragora autumnalis poisoning: diagnosis and treatment.
AB  - A multiple case of Mandragora autumnalis poisoning is described. Mandragora
      autumnalis, a solanaceous plant that is common in the Sicilian countryside,
      contains a variable concentration of solanum alkaloids, which cause
      gastrointestinal irritation, and tropane alkaloids, which have anticholinergic
      properties and produce typical and sometimes severe atropine-like symptoms. Vital
      function support, decontamination, symptomatic treatment and, in severe cases,
      antidote therapy with physostigmine are useful to control acute poisoning.

PMID- 12501036
TI  - Near-hanging.
AB  - Each year, thousands of people are strangled. Survival from strangulation or
      hanging is often associated with various complications including a large variety
      of neurological consequences. As it is common knowledge that the GCS and other
      initial presenting findings bear a poor correlation to the ultimate outcome,
      aggressive resuscitation and treatment of post anoxic brain injury is indicated
      in every patient in absence of definite signs of death and irrespective of the
      duration of hypoxia or unconsciousness in cases of strangulation, especially in
      cases of suicidal near-hanging. These case reports describe two near-hanging
      episodes in patients with a normal neurological outcome.

PMID- 12501037
TI  - Management strategy of chest pain patients with or without evidence of acute
      coronary syndrome in the emergency department.

PMID- 12501038
TI  - Are women who are Jehovah's Witnesses at risk of maternal death?

PMID- 12501040
TI  - Using the TDx-FLM assay and gestational age together for more accurate prediction
      of risk for neonatal respiratory distress syndrome.

PMID- 12501041
TI  - Equilibrium.

PMID- 12501042
TI  - Povidone-iodine spray technique versus traditional scrub-paint technique for
      preoperative abdominal wall preparation.
AB  - OBJECTIVE: The study was conducted to compare povidone-iodine spray and
      traditional scrub-paint techniques in reducing abdominal wall bacteria during
      preoperative preparation. STUDY DESIGN: Sixty patients scheduled to undergo
      vaginal surgery were recruited for study. Cultures of the abdominal skin were
      performed before and after preparation with two techniques: A traditional 5
      minute iodophor soap scrub-paint on one half and povidone-iodine aqueous spray on
      the other. Multiple pairwise comparisons were performed with the Wilcoxon signed
      rank test. A P value of.05 was considered statistically significant in all
      analyses. RESULTS: The mean number of colonies for spray after 1 minute was 1.83
      +/- 3.16, for spray after 3 minutes was 0.40 +/- 1.15, and after 5-minute scrub
      was 0.87 +/- 2.97. Both techniques, the spray after 3 minutes and the 5-minute
      scrub, were statistically more effective at reducing bacterial counts than the
      spray after 1 minute. There was no statistically significant difference between
      the spray after 3 minutes and the scrub techniques. CONCLUSION: Povidone-iodine
      applied as a spray and left to dry for 3 minutes appears as effective as the
      traditional scrub-paint technique in reducing abdominal wall bacteria before
      abdominal surgery.

PMID- 12501043
TI  - Mechanical performance of knots using braided and monofilament absorbable
      sutures.
AB  - OBJECTIVE: The study was undertaken to test the integrity of various flat and
      sliding knots with the use of braided and monofilament absorbable sutures. STUDY
      DESIGN: There were four study groups, each of which consisted of a single suture
      type and size, with five different knots. Each combination was tested 10 times
      for a total of 200 experiments. The suture types used were 0-0 and 2-0 Glycomer
      631 (Biosyn) and 0-0 and 2-0 coated Lactomer (Polysorb). Knots tested were the
      square knots, surgeon's knots, modified granny flat knots, and modified identical
      and nonidentical sliding knots. Knots were tested to failure with a tensiometer.
      We compared the proportion of knots becoming untied within each group and the
      ultimate load required to break tied knots. RESULTS: In the 0-0 and 2-0 Lactomer
      groups, 90% and 60% of modified identical sliding knots, respectively, became
      untied, significantly more than all other knots. CONCLUSION: When 0-0 and 2-0
      Lactomer sutures were used, modified identical sliding knots should be avoided.

PMID- 12501044
TI  - Posterior vaginal wall defects and their relation to measures of pelvic floor
      neuromuscular function and posterior compartment symptoms.
AB  - OBJECTIVE: The purpose of this study was to describe the pelvic floor
      neuromuscular function and posterior compartment symptoms in patients with
      posterior vaginal wall prolapse. STUDY DESIGN: Two hundred twenty-seven women who
      were referred to a urogynecology and urology clinic were enrolled prospectively.
      Each patient completed a health history questionnaire and standardized physical
      examination that specifically graded uterovaginal prolapse according to the
      pelvic organ prolapse quantification system. RESULTS: Sixty-nine women had a
      pelvic organ prolapse quantification system point (most dependent portion of the
      posterior vaginal wall during straining as measured from the hymeneal ring) of <
      or =-1. Older age, a history of hysterectomy, a genital hiatus of >3 cm (48% vs
      24%; P =.002), and perineal descent of > or =2 cm (14% vs 5%; P =.042) were
      significantly more common in women with posterior vaginal prolapse. When women
      with posterior prolapse and symptomatic complaints were compared with
      asymptomatic women with prolapse, a perineal descent of > or =2 cm (21% vs 0%; P
      =.004) was significantly more common in the symptomatic group. CONCLUSION: Pelvic
      floor neuromuscular function should be related to posterior vaginal prolapse and
      symptoms; however, only perineal descent appears associated strongly with both
      symptoms and prolapse in this population.

PMID- 12501045
TI  - The effect of ketorolac on postoperative febrile episodes in patients after
      abdominal myomectomy.
AB  - OBJECTIVE: Our purpose was to determine whether administering the anti
      inflammatory agent ketorolac after abdominal myomectomy reduces the incidence of
      febrile episodes. STUDY DESIGN: This prospective, randomized, double-blinded,
      placebo-controlled clinical investigation compared administering ketorolac 15 mg
      intravenously every 6 hours beginning in the recovery room with saline solution
      administered in the same regimen in 122 patients undergoing abdominal myomectomy
      in a large, urban academic medical center. The primary outcome was fever >101.0
      degrees F in the postoperative period. Results were analyzed by chi(2) analysis,
      independent samples t test, and logistic regression. RESULTS: Data were analyzed
      on 112 patients, with 56 in the treatment group and 56 in the placebo group.
      After confounding factors were controlled with logistic regression, the data
      revealed a statistically significant reduction in febrile episodes in the
      ketorolac-treated group (27%) compared with the saline solution-treated group
      (41%) (P =.04). CONCLUSION: Treatment with ketorolac after abdominal myomectomy
      results in a statistically significant reduction in the rate of febrile episodes.

PMID- 12501046
TI  - Metabolic regulation of collagen I in fibroblasts isolated from normal peritoneum
      and adhesions by dichloroacetic acid.
AB  - OBJECTIVE: We have previously demonstrated that collagen I, a major component of
      postoperative adhesions, is differentially regulated in fibroblasts isolated from
      normal human peritoneum and adhesions. Collagen I messenger RNA (mRNA) levels are
      significantly lower in fibroblasts from normal peritoneum compared with levels
      from adhesion fibroblasts. This variation is further accentuated by hypoxia.
      Because adhesions provide a means of supplying oxygen and nutrients to
      postsurgical ischemic tissue, we sought to examine the role of aerobic metabolism
      in the differential expression of collagen I. To examine this issue, we used a
      compound, dichloroacetic acid (DCA), that stimulates pyruvate dehydrogenase,
      causing pyruvate to be metabolized in the Kreb's cycle rather than converted into
      lactate, thereby switching anaerobic to aerobic metabolism. Specifically, we have
      exposed human fibroblast cultures from normal peritoneum and adhesions to DCA (0,
      50, and 100 microg/mL) for 24 hours under normal and hypoxic (2% oxygen)
      conditions. STUDY DESIGN: Multiplex reverse transcriptase-polymerase chain
      reaction (RT-PCR) of collagen I and beta-actin was performed by using mRNA
      extracted from all treatment points. Analysis of PCR-amplified products was
      performed by fractionation over a 2% agarose gel, followed by ethidium bromide
      staining of DNA bands. A scanning densimeter was used to determine the ratio of
      intensity of each band relative to beta-actin. Densimetric analysis of gel bands
      was performed by using the National Institutes of Health image analysis program.
      RESULTS: Although DCA stimulated peritoneal fibroblast collagen I mRNA expression
      under normoxic conditions, its expression was reduced during hypoxia. In adhesion
      fibroblasts, DCA treatment consistently lowered collagen I mRNA expression; this
      effect was manifested to a greater extent under hypoxic conditions. CONCLUSION:
      In summary, these findings confirm that fibroblasts from adhesions are
      characterized by excessive collagen I production, which is further accentuated by
      hypoxia. These observations are extended to show the stimulation of oxidative
      metabolism by DCA increases collagen I production; in contrast DCA inhibits
      collagen I production by normoxic adhesion fibroblasts as well as under hypoxic
      conditions in both types of fibroblasts. Thus, regulation of metabolic activity
      of peritoneal cells may provide a target for future interventions for reduction
      of postoperative adhesions.

PMID- 12501047
TI  - Sacral neuromodulation in an older, urge-incontinent population.
AB  - OBJECTIVE: The success of sacral neuromodulation in the treatment of urge
      incontinence has been reported in young populations. Herein we report the success
      in an older, urge-incontinent population. STUDY DESIGN: A cohort of 25 patients
      older than 55 years who had failed conventional therapy for the treatment of urge
      incontinence underwent percutaneous S3 sacral nerve test stimulation. Patients
      were considered candidates for permanent implantation if they were cured or had a
      greater than 50% improvement in incontinent episodes. Responders were implanted
      and completed a questionnaire, bladder diary, and disease-specific quality-of
      life questionnaire. RESULTS: Twelve of the 25 patients (48%) responded to the
      test stimulation. The average follow-up after permanent implantation was 7.8
      months. All patients obtained a >50% reduction in their incontinent episodes; 2
      patients achieved total dryness. CONCLUSION: Our small cohort suggests that older
      urge-incontinent patients have improvement with sacral neuromodulation but cure
      rates may be lower than with a younger population.

PMID- 12501048
TI  - The use of intraoperative cystoscopy in major vaginal and urogynecologic
      surgeries.
AB  - OBJECTIVE: Our purpose was to examine the frequency of significant intraoperative
      cystoscopic findings during major vaginal reconstructive and urogynecologic
      surgeries. STUDY DESIGN: The records of 526 consecutive women who underwent
      routine cystoscopy with intravenous injection of indigo carmine at the time of
      their urogynecologic and major vaginal reconstructive procedures between January
      1, 1997, and April 20, 2001, were reviewed. We determined the incidence of
      significant cystoscopic findings and their effect on intraoperative management.
      Two-tailed t tests and logistic regression analyses were used to compare
      characteristics between the groups with and without significant cystoscopic
      findings. RESULTS: During the 526 operations, 26 significant findings (4.9%) were
      unsuspected before cystoscopy and 15 (2.9%) of these findings were operative
      injuries that required intervention. Seventy-nine subjects (15.0%) had no anti
      incontinence operation performed. Of these patients, there was one partial
      ureteral obstruction from an anterior colporrhaphy (1.3%). Seven of 184 Burch
      procedures (3.8%) resulted in injuries to the lower urinary tract, of which 3
      (1.6%) required intervention that were unrecognized before cystoscopy. Seven of
      the 15 cases resulting in changes in intraoperative management were caused by
      anterior colporrhaphy sutures (2.0% of all anterior colporrhaphies). There were
      no unrecognized injuries that caused morbidity after surgery. There were no
      significant differences between patients with abnormal and normal cystoscopic
      findings in regard to mean age, weight, parity, estimated blood loss, previous
      surgery, or previous incontinence surgeries. No complications or morbidity
      occurred as a direct result of intraoperative cystoscopy. CONCLUSION:
      Intraoperative cystoscopy with intravenous indigo carmine is a safe and effective
      way to detect injury of the lower urinary tract. Cystoscopy detected unsuspected
      operative injuries in 2.9%. In cases that did not involve anti-incontinence
      procedures, the rate of injury was 1.3%. With a significant rate of detection,
      cystoscopy allows for immediate recognition and easier repair of lower urinary
      tract injury, lowering the patient's risk for morbidity. Anterior colporrhaphy
      was the most common cause of unrecognized ureteral compromise.

PMID- 12501049
TI  - Long-term success of abdominal sacral colpopexy using synthetic mesh.
AB  - OBJECTIVE: The aim was to determine the minimum meaningful study period required
      for prospective trials involving sacral colpopexy. STUDY DESIGN: This is a
      retrospective analysis of 245 patients who underwent sacral colpopexy.
      Postoperative pelvic organ prolapse quantitation was our objective end point. In
      an effort to control for selection bias, patients who returned for postoperative
      examinations were compared with those who did not for clinical and demographic
      information. A validated prolapse-specific quality of life instrument was used to
      determine the subjective end points. RESULTS: Objective failure (any
      postoperative POP-Q point > or = stage II) was found in 37 (15.1%) patients. Of
      these, 26 (70.3%) occurred within 6 months, and 30 (81.1%) occurred within 1
      year. Another 5 objective failures were discovered between 1 and 2 years after
      surgery for a total of 94.6% of failures occurring within 2 years. There were no
      clinically significant differences between the groups of women with and without
      objective postoperative follow-up, indicating minimal selection bias. CONCLUSION:
      It is reasonable to construct randomized controlled trials involving sacral
      colpopexy that only include 1- or 2-year follow-up.

PMID- 12501050
TI  - Does hysterectomy without adnexectomy in patients with prior tubal interruption
      increase the risk of subsequent hydrosalpinx?
AB  - OBJECTIVE: Our purpose was to examine the hypothesis that hysterectomy without
      adnexectomy after tubal interruption is associated with the development of
      hydrosalpinx. STUDY DESIGN: In this case-control study, patients with a
      pathologic diagnosis of hydrosalpinx were compared with a group of patients
      undergoing adnexectomy without a hydrosalpinx. The incidence of prior tubal
      interruption followed by hysterectomy in the two groups was compared. RESULTS:
      There was a statistically significant association between the development of
      hydrosalpinx and a history of hysterectomy after tubal interruption. Nine of 38
      cases and 2 of 45 controls had a history of tubal interruption (odds ratio 6.67,
      P =.019). CONCLUSIONS: Patients undergoing hysterectomy who have had a tubal
      interruption may be at risk for the development of hydrosalpinx because this
      combination of procedures results in a segment of tube that is blocked at both
      ends. If further study bears out this association, consideration should be given
      to performing salpingectomy at the time of hysterectomy even if the ovaries are
      being left behind.

PMID- 12501051
TI  - Longitudinal impact of a female pelvic medicine and reconstructive pelvic surgery
      fellowship on resident education.
AB  - OBJECTIVE: The purpose of this study was to assess residents' perceptions of the
      impact of a new fellowship on their educational experience. STUDY DESIGN: A
      voluntary questionnaire was administered to residents in obstetrics and
      gynecology that assessed how they felt fellowships in female pelvic medicine and
      reconstructive surgery had an impact on their education. The initial
      questionnaire was given within 1 month of the beginning a new 3-year fellowship
      and then annually for 3 years. RESULTS: The mean response rate was 32%. In the
      initial questionnaire, the fellowships were perceived as detracting from the
      educational experience. Thereafter, there was a positive increase in the
      perceived impact of fellowships that was sustained for 3 years. Residents also
      reported higher self-assessments of the quality of their education during this
      period. Residents' surgical volume did not change with the introduction of the
      fellowship. CONCLUSION: Although at the outset residents anticipated the addition
      of a fellowship to have a negative impact on their educational experience, they
      consistently reported a positive impact after the fellowship was instituted.

PMID- 12501052
TI  - Incidence of occult rectal prolapse in patients with clinical rectoceles and
      defecatory dysfunction.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence of occult
      rectal prolapse (rectal intussusception) by defecating proctography in patients
      with clinical rectoceles and defecatory dysfunction. STUDY DESIGN: Patients who
      were seen from September 2000 through August 2001 with defecatory dysfunction and
      clinical rectoceles underwent single contrast defecating proctography.
      Radiologists who specialized in gastrointestinal fluoroscopy interpreted the
      results, which were retrieved from a computerized database. Study Design: Sixty
      patients who met the inclusion criteria were evaluated. Twenty patients (33%) had
      intussusception; 58 patients (97%) had rectocele; 1 patient (1.7%) had
      sigmoidocele, and 6 patients (10%) had anismus (paradoxic contraction of the
      puborectalis). RESULTS: All but 1 case of intussusception was associated with a
      rectocele radiographically. Anismus was associated with rectoceles
      radiographically, except in 1 patient for whom it was the sole finding.
      CONCLUSION: The data suggest a 33% incidence of occult rectal prolapse in
      patients with clinical rectoceles and defecatory dysfunction. This is highly
      clinically significant because one third of patients who are examined for
      defecatory dysfunction and rectocele may require sigmoid resection rectopexy
      along with other reconstructive procedures to restore pelvic floor function and
      prevent symptomatic recurrence.

PMID- 12501053
TI  - Morphometric properties of the posterior vaginal wall in women with pelvic organ
      prolapse.
AB  - OBJECTIVE: Our purpose was to analyze the morphometric properties of the
      posterior vaginal wall and compare the smooth muscle distribution in the
      posterior vaginal muscularis in women with and without pelvic organ prolapse.
      STUDY DESIGN: Specimens were taken from the apex of the posterior vaginal wall
      after hysterectomy from 15 women with pelvic organ prolapse and from 8 healthy
      control subjects. Smooth muscle cells of the posterior vaginal wall were
      identified by immunohistochemistry with antibodies to smooth muscle alpha-actin.
      Morphometric analysis was performed on histologic cross-sections of the posterior
      vaginal wall to determine the fractional area of nonvascular smooth muscle in the
      muscularis. The innervation pattern of the vaginal wall was determined by use of
      S100 immunostaining. Statistical comparisons between two groups were conducted by
      a Student t test. Comparisons between multiple groups were conducted with a one
      way analysis of variance followed by a post-hoc Student-Neuman-Keuls test.
      RESULTS: The fractional area of nonvascular vaginal smooth muscle in the
      muscularis of women with posterior wall prolapse was significantly decreased
      compared with that of healthy control subjects. Nerve bundles were located in the
      deep vaginal muscularis and adventitia of the posterior vaginal wall. In women
      with posterior wall prolapse, nerve bundles were smaller and fewer in number.
      CONCLUSION: Morphologic features of the posterior vaginal wall are significantly
      altered in women with posterior wall prolapse compared with asymptomatic control
      subjects.

PMID- 12501054
TI  - Formation of vesicovaginal fistulas in laparoscopic hysterectomy with
      electrosurgically induced cystotomy in female mongrel dogs.
AB  - OBJECTIVE: The aim of this pilot study was to investigate the relationship
      between various types of laparoscopic bladder injuries and vesicovaginal fistula
      formation in an animal model. STUDY DESIGN: Sixteen female mongrel dogs were
      divided into four groups. All animals underwent a laparoscopic hysterectomy.
      Those assigned to group 1 sustained a 1-cm bipolar cautery injury to the bladder
      base without perforation of the bladder mucosa. Animals in group 2 had two
      sutures of 2-0 polyglactin placed to incorporate the full thickness of the
      bladder wall and the vaginal cuff. The bladder injury to group 3 was a 1-cm
      bladder base laceration induced with monopolar cautery, repaired with two
      interrupted 2-0 polyglactin sutures. Group 4 underwent a bladder base cystotomy
      similar to those in group 3, with the closure incorporating the anterior vaginal
      wall. Animals were killed and necropsy was performed at least 28 days after
      surgery. The bladder and vagina of each animal were harvested en bloc. Evidence
      of a vesicovaginal fistula was determined by two methods: transurethral injection
      of indigo carmine solution under direct visualization and air injection during
      underwater submersion. RESULTS: The four groups were comparable with regard to
      postoperative weight changes. No mongrels showed signs of infection or sepsis.
      Inspection of the harvested bladder and vagina revealed no fistulas in groups 1
      and 2. One mongrel from group 3 and one from group 4 had evidence of a
      vesicovaginal fistula. With 95% CIs, the fistula rate would be at least 2% and as
      high as 38% if a larger study had been undertaken. CONCLUSION: The female mongrel
      is the first identified animal model of vesicovaginal fistula formation. In this
      setting, an electrosurgically induced cystotomy and repair of the bladder during
      the performance of a laparoscopic hysterectomy is associated with the formation
      of postoperative vesicovaginal fistulas.

PMID- 12501055
TI  - Differences in uterine innervation at hysterectomy.
AB  - OBJECTIVE: Our purpose was to identify patterns of uterine innervation in normal
      uteri and selected clinical conditions including adenomyosis and chronic pelvic
      pain. STUDY DESIGN: A retrospective survey was performed of stored uteri removed
      at hysterectomy for a variety of clinical conditions, including 8 uteri from
      nulliparous subjects (group 1, mean age 40.0 years, range 30-52 years), 21 uteri
      with no reported histologic abnormality from multiparous subjects (group 2, mean
      age 43.4 years, range 32-53 years; mean parity 2.0, range 1-4), 31 uteri reported
      with adenomyosis (group 3, mean age 42.4 years, range 29-54 years; parity 2.0,
      range 0-4), and 17 uteri from subjects with pelvic pain (group 4, mean age 39.1
      years, range 30-52 years; parity 2.5, range 1-7). Sections were cut from paraffin
      blocks of the isthmus of stored uteri (in the majority of cases) and stained with
      protein gene product 9.5 to identify nerves. Sections of pancreas provided
      positive controls. Each section was reviewed by two unblinded observers. RESULTS:
      Group 1 (n = 8, nulliparous uteri) showed significant nerve bundles at the
      endometrial-myometrial interface and in the subserosal layers, with nerve fibers
      noted in intervening neurovascular bundles supplying the myometrial stroma. Group
      2 (n = 21, histologically normal uteri from parous subjects) showed patterns of
      innervation similar to those of group 1 with the exception that 6 uteri
      demonstrated areas of nerve fiber proliferation (see below, group 4). In group 3
      (n = 31, uteri with adenomyosis), 30 uteri (30/31) showed large areas of
      myometrium without nerves and absence of nerves in the neurovascular bundles
      supplying these areas. Five uteri showed areas of nerve fiber proliferation at
      the margins of the adenomyosis. Subserosal nerves were present in the majority of
      these uteri. In group 4 (n = 17), uteri were removed for chronic pelvic pain.
      Eleven uteri demonstrated proliferation of small-diameter nerve fibers throughout
      the myometrium; in 6 uteri there was asymmetry of nerve fiber proliferation.
      CONCLUSIONS: Variations in uterine innervation were noted in the isthmic region
      of uteri stored after hysterectomy. Uteri with adenomyosis frequently
      demonstrated large areas with absence of nerve fibers; uteri from subjects with
      chronic pelvic pain showed proliferation of small-diameter nerve fibers
      throughout the myometrial stroma. Nerve fiber proliferation was asymmetric in
      some of these specimens.

PMID- 12501056
TI  - Guidelines for the selection of the route of hysterectomy: application in a
      resident clinic population.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of the
      Society of Pelvic Reconstructive Surgeons guidelines for the determination of the
      route of hysterectomy in a resident clinic population. STUDY DESIGN: A total of
      407 consecutive women from the resident clinic population at Wright State
      University between October 1, 1994, and December 31, 1999, were assigned
      prospectively to abdominal or vaginal hysterectomy groups according to Society of
      Pelvic Reconstructive Surgeons guidelines. The women's age, race, and
      preoperative and postoperative uterine weights, length of stay, laparoscopic
      scores, operative time, and complications were compared. RESULTS: Vaginal
      hysterectomy was completed successfully in 91.8% of the women. As expected,
      vaginal hysterectomy required the shortest operative time and length of stay and
      was associated with fewer complications than the abdominal approach (P <.01).
      Laparoscopic assistance was necessary in 25.8% of patients to assess extrauterine
      disease. CONCLUSION: Resident physicians who followed the practice guidelines
      reduced the ratio of abdominal-to-vaginal hysterectomy from 3:1 to 1:11. The
      application of practice guidelines for the selection of the route of hysterectomy
      can increase the ratio of vaginal hysterectomies that are performed in residency
      programs and can help eradicate inconsistencies in health care delivery that
      exist currently.

PMID- 12501057
TI  - Satisfaction with hysterectomy: low-income underinsured teaching hospital
      patients versus insured patients at a private hospital.
AB  - OBJECTIVE: The purpose of this study was to measure patient health-related
      quality of life/satisfaction with the results of hysterectomy in 2 distinct
      groups of women. STUDY DESIGN: A health-related outcomes questionnaire was
      completed 3 months after hysterectomy by 50 low-income women who underwent
      operation at a state-supported teaching hospital and by 50 women who underwent
      operation at a private hospital. RESULTS: The women at the teaching hospital had
      a significantly worse outcome satisfaction score than the women at a private
      hospital. However, 98% of the patients at the teaching hospital and 100% of
      patients at the private hospital noted their symptoms to be improved. Factors
      such as race, age, preoperative indications, route of hysterectomy, oophorectomy,
      and hormone replacement therapy did not affect outcome scores. CONCLUSION: Low
      income women who undergo operation at a university teaching hospital experience
      lower satisfaction after hysterectomy than do other women.

PMID- 12501058
TI  - The centrality of the clinician in the evaluation of patients with abnormal
      cervical cytologic studies.
AB  - The management of women with abnormal cervical cytologic studies requires in
      depth knowledge of the patient and the disease, as well as the illness caused by
      their interaction. Only the clinician has access to these three parameters.
      Therefore, recommendations regarding patient care made by the cytology laboratory
      that appear on the cytology report are often inappropriate, may lead to
      mismanagement, and have the potential for disruption of the physician-patient
      relationship. Even suggestions based on guidelines that are evidence based often
      do not apply to a particular patient because such guidelines are most appropriate
      for only the "average" patient.

PMID- 12501059
TI  - Emergency contraception and fire extinguishers: a prevention paradox.
AB  - Fires and unintended pregnancies are important causes of morbidity, mortality,
      and financial loss in the United States. Home fire extinguishers and emergency
      contraception are both effective preventive interventions. The disparity between
      access to fire extinguishers and emergency contraception is irrational and
      indirectly hurts women's health. Although fire extinguishers require the user to
      make a diagnosis, choose the appropriate treatment, and assume some risk of
      serious injury and death, these canisters of pressurized chemicals are widely
      available without restriction. In contrast, women face several unnecessary
      obstacles to overcome before using emergency contraception, which is both simpler
      and safer to use. Clearly, a double standard prevails in prevention strategies
      for women. The Food and Drug Administration should approve over-the-counter
      availability of emergency contraception without further study or delay.

PMID- 12501060
TI  - A survey of recommendations by gynecologists in Canada regarding oral
      contraceptive use in the perioperative period.
AB  - OBJECTIVE: This survey was conducted to determine the practice patterns of
      gynecologists in Canada regarding the discontinuation of oral contraceptives
      before gynecologic surgical procedures. STUDY DESIGN: In May and June of 1997,
      surveys were sent to all obstetricians and gynecologists on the mailing list of
      the Society of Obstetricians and Gynaecologists of Canada. RESULTS: Of the 1472
      surveys that were sent, 702 of the surveys were completed and returned, for a
      response rate of 48%. More than 90% of the gynecologists who were surveyed would
      advise their patients to continue using oral contraceptives before relatively
      minor surgical procedures and <1% of them would use low-dose heparin before these
      procedures. Rates of oral contraceptive discontinuation increased as the extent
      of the surgical intervention increased: Prolonged laparoscopy (39.8%), vaginal
      repairs and hysterectomy (54.7%), and abdominal hysterectomy or adnexectomy
      (56.1%). Just over one half of the gynecologists (56.1%) indicated that they
      would advise discontinuation > or =4 weeks before the surgical procedure, which
      is the minimum time required for the prothrombotic changes that are associated
      with oral contraceptive use to return to baseline. Less than 10% of the surgeons
      indicated that they would use low-dose heparin even when the patient was advised
      to continue taking oral contraceptives before major surgical procedures.
      CONCLUSION: The controversy over whether young healthy women should discontinue
      oral contraceptive use before major surgical procedures that are associated with
      immobility is reflected by a lack of consensus among gynecologists in Canada.

PMID- 12501061
TI  - Estradiol suppresses vascular monocyte chemotactic protein-1 expression during
      early atherogenesis.
AB  - OBJECTIVE: This study was undertaken to determine whether estrogen down-regulates
      vascular monocyte chemotactic protein-1 expression during the development of
      atherosclerosis in vivo and to identify the cellular localization of monocyte
      chemotactic protein-1 expression under baseline conditions and in response to
      atherogenic stimuli. STUDY DESIGN: Female, homozygous low-density lipoprotein
      receptor-deficient mice (n = 68) in a C57BL/6 background underwent ovariectomy,
      were implanted subcutaneously with 17beta-estradiol or placebo pellets, and were
      changed to a high cholesterol (1.25%) diet. Thereafter, four mice from each group
      were killed weekly for 8 weeks, and their aortae were frozen for
      immunohistochemical analysis. The lipid deposition was identified by Sudan black
      B staining. Monocyte chemotactic protein-1 expression was detected with a rabbit
      anti-mice monocyte chemotactic protein-1 antibody, and semiquantitative analysis
      was performed. RESULTS: Consistent with previous reports, estradiol resulted in
      diminished vascular lipid deposition (22% +/- 7% vs 15% +/- 6% at 8 weeks of
      gestation, P <.05). We found that the inhibition of lipid deposition in aortae of
      animals that were treated with estrogen is associated with a concomitant down
      regulation of monocyte chemotactic protein-1 immunoreactivity in aortic
      endothelial and smooth muscle cells (P <.05). Serum total cholesterol
      concentrations did not differ between the two treatment groups, which suggests a
      direct effect of estradiol on the aorta. CONCLUSION: Our findings suggest that
      one of the mechanisms by which estrogen down-regulates atherogenesis is by the
      suppression of vascular monocyte chemotactic protein-1 expression, which leads to
      decreased macrophage recruitment to the arterial wall early in the process.

PMID- 12501062
TI  - Type III female genital mutilation: clinical implications and treatment by carbon
      dioxide laser surgery.
AB  - OBJECTIVE: The purpose of this study was to examine clinical implications of type
      III female genital mutilation and to evaluate the use of carbon dioxide laser
      surgery to restore vulvar opening and to treat associated epithelial inclusion
      cysts. STUDY DESIGN: Twenty-five infibulated patients underwent carbon dioxide
      laser treatment. Seven of the women (28%) were pregnant, between 10 and 37 weeks
      of gestation. Vulvar examination revealed five cases of epidermal inclusion
      cysts. One pregnant patient, with a cyst that was 7 cm in diameter, was at 24
      weeks of gestation. Deinfibulation was performed in an outpatient setting with
      local anesthesia. A colposcopy-guided laser beam was used to create an incision
      along the fusion midline of the labia majora. In case of vulvar epidermal
      inclusion cyst, the capsule was opened and emptied of sebaceous contents; the
      inner surface of the cyst was vaporized completely. RESULTS: The carbon dioxide
      laser procedure restored a complete vulvar opening in all 25 patients. The
      complete vaporization of cyst capsule was possible in all five cases. No case of
      intraoperative or postoperative complication occurred. The average duration of
      follow-up was 11 months. Four patients who underwent deinfibulation antenatally
      had labor with spontaneous vaginal delivery and no evidence of perineal trauma.
      CONCLUSION: On the basis of the advantages that were observed, deinfibulation
      treatment must be offered to all infibulated patients. The procedure is
      particularly appropriate during pregnancy to prevent childbirth complications.
      Laser carbon dioxide has been proved to be a suitable technique for the treatment
      of female genital mutilation when inclusion cysts are associated with it.

PMID- 12501063
TI  - Differential effects of selective estrogen receptor modulators and estrogens on
      mammary blood flow in the ovine.
AB  - OBJECTIVE: Hormone replacement therapy has been implicated in the increased
      incidence of breast cancer, although selective estrogen receptor modulators have
      been shown to be effective in the prevention of breast cancer. Breast cancers are
      associated with increased mammary blood flow compared to benign breast lesions.
      However, few studies have examined the hemodynamic effects of hormonal agents on
      the mammary circulation that promote or reduce the risk of breast cancers.
      Although estradiol-17beta has been shown to increase mammary blood flow, the
      effect of selective estrogen receptor modulators remains undetermined. We
      therefore compared the vascular effects of selective estrogen receptor modulators
      and estrogens on mammary blood flow. STUDY DESIGN: Fourteen nonpregnant
      ovariectomized ewes were instrumented to measure mean arterial pressure, heart
      rate, and uterine and mammary blood flows. Compounds were administered
      intravenously on separate days, and responses were monitored up to 4 hours.
      Compounds that were studied included estradiol-17beta (1 microg/kg), conjugated
      equine estrogens (0.625 and 1.25 mg), tibolone (2.5 and 5 mg), raloxifene (10
      microg/kg), and tamoxifen (300 microg/kg). RESULTS: None of these compounds
      significantly affected mean arterial pressure or heart rate, but all of the
      compounds significantly increased uterine blood flow. Estradiol-17beta increased
      mammary blood flow by 98% +/- 25%; conjugated equine estrogen increased mammary
      blood flow by 46% +/- 6% and 68% +/- 13% at the 0.625 and 1.25 mg doses,
      respectively. Tibolone increased mammary blood flow by 37% +/- 13% at the 2.5-mg
      dose and by only 14% +/- 4% at the 5-mg dose. Neither raloxifene nor tamoxifen
      significantly altered mammary blood flow. CONCLUSION: Although estrogens and
      selective estrogen receptor modulators induced similar increases in uterine blood
      flow, they had differential effects on mammary blood flow.

PMID- 12501064
TI  - Abdominal or vaginal hysterectomy for enlarged uteri: a randomized clinical
      trial.
AB  - OBJECTIVE: The purpose of this study was to compare advantages, disadvantages,
      and outcomes in patients who undergo vaginal or abdominal hysterectomy for
      enlarged symptomatic uteri. STUDY DESIGN: In a prospective, randomized study, 60
      vaginal hysterectomies (study group) were compared with 59 abdominal
      hysterectomies (control group); all of the hysterectomies were performed for
      symptomatic uterine fibroids from January 1997 through December 2000. We excluded
      from the study the other common causes of hysterectomy such as prolapse,
      bleeding, adenomyosis, and endometrial or cervical carcinoma. In both groups,
      uterine weights ranged from 200 g to 1300 g. For enlarged uteri, vaginal
      hysterectomies were performed with the use of volume reduction techniques:
      Intramyometrial coring, corporal bisection, and morcellation. The evaluated
      parameters included patient age, weight, parity, uterine weight, operative time,
      blood loss, demand for analgesics, eventual surgical complications, length of
      admission, and hospital charges. The Mann-Whitney U test and chi(2) tests were
      applied for statistical analysis. Probability values of <.05 were considered
      statistically significant. RESULTS: There were no major differences in patient
      age, weight, parity, and uterine weight between the two groups. Operative time
      was significantly lower for the vaginal route as compared with the abdominal
      route (86 minutes vs 102 minutes, P <.001). No intraoperative complications were
      noted both in the study and control groups or the control group. Surgical
      bleeding (expressed by hemoglobin loss) was not significantly different between
      the two groups. In the postoperative period, we found a higher incidence of fever
      (30.5% vs 16.6%, P <.05) and demand for analgesics (86% vs 66%, P <.05) in the
      abdominal group as compared with the vaginal group. Significant advantages of
      vaginal hysterectomy were a reduction in the hospital stay (3 days vs 4 days, P
      <.001) and cost. CONCLUSION: These results should lead to the choice of vaginal
      hysterectomy as a valid alternative to the abdominal hysterectomy, even for
      enlarged uteri.

PMID- 12501065
TI  - Cytometric features of cell nuclei of adenocarcinoma in situ and invasive
      adenocarcinoma of the cervix.
AB  - OBJECTIVE: The goal of this study was to characterize adenocarcinoma in situ
      (ACIS) and invasive adenocarcinoma (AdCa) of the cervix by using image
      histometric measurements of nuclear morphometric features. STUDY DESIGN: Archival
      pathology slides and tissue blocks from 37 patients with ACIS, 18 with invasive
      AdCa, and 13 with normal cervical epithelial and glandular histology were
      reviewed by two pathologists. The controls were matched for age and menstrual
      status and as closely as possible for the age of the slides; this limited the
      number of normal cases available. Morphometric, photometric, and textural
      measurements were made on 4-microm sections of tissue stained with a thionin
      SO(2) Feulgen reaction. A mixed analysis of covariance model was used for
      analysis. RESULTS: The Integrated Optical Density Index was found between the
      mean value for normal cells and that for ACIS and invasive AdCa (P <.001). Twenty
      two other morphometric features were identified that exhibited differences in
      their means between at least two of the three tissue types. CONCLUSION: In the
      cell populations studied, certain nuclear image features were found to correlate
      with histologic diagnosis. The features can be measured objectively and could be
      useful to pathologists in differentiating lesions, although a larger study should
      be evaluated to confirm these findings. Further, these features may be important
      as optical technologies are developed that make diagnoses in real time.

PMID- 12501066
TI  - Modulation of trophoblast function by tumor necrosis factor-alpha: a role in
      pregnancy establishment and maintenance?
AB  - OBJECTIVE: Trophoblast differentiation is a critical process for successful
      implantation and establishment of the human placenta. The aim of this study was
      to characterize the effect of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) on the expression of markers of trophoblast function and
      differentiation. STUDY DESIGN: Human cytotrophoblasts were stimulated with 1 and
      10 ng/mL recombinant TNF-alpha or IL-6. Cell viability was determined and
      conditioned culture media was analyzed by gelatin zymography to assess protease
      secretion and by enzyme-linked immunosorbent assays to measure production of beta
      human chorionic gonadotropin and oncofetal fibronectin. RESULTS: TNF-alpha
      increased secretion of urokinase-type plasminogen activator up to 3-fold of basal
      unstimulated production. Stimulation of cytotrophoblasts with this cytokine also
      inhibited beta-human chorionic gonadotropin secretion up to 75%. TNF-alpha did
      not modify the secretion of matrix metalloproteinase-9 and oncofetal fibronectin.
      IL-6 had no effect on these trophoblast differentiation markers. CONCLUSION:
      These results show that TNF-alpha stimulated cytotrophoblasts modulate the
      expression of differentiation markers, down-regulating the autocrine signals that
      promote syncytialization, and increasing their invasive capacity through up
      regulation of proteases. We suggest that this regulatory mechanism of trophoblast
      function could play an important role during trophoblast implantation, in
      pregnancy failure and in the normal and pathologic rupture of fetal membranes.

PMID- 12501067
TI  - Efficacy of static magnetic field therapy in chronic pelvic pain: a double-blind
      pilot study.
AB  - OBJECTIVE: The aim of the study was to determine the efficacy of static magnetic
      field therapy for the treatment of chronic pelvic pain (CPP) by measuring changes
      in pain relief and disability. STUDY DESIGN: Thirty-two patients with CPP
      completed 2 weeks and 19 patients completed 4 weeks of randomized double-blind
      placebo-controlled treatment at a gynecology clinic. Active (500 G) or placebo
      magnets were applied to abdominal trigger points for 24 hour per day. The McGill
      Pain Questionnaire, Pain Disability Index, and Clinical Global Impressions Scale
      were outcome measures. RESULTS: Patients receiving active magnets who completed 4
      weeks of double-blind treatment had significantly lower Pain Disability Index (P
      <.05), Clinical Global Impressions-Severity (P <.05), and Clinical Global
      Impressions-Improvement (P <.01) scores than those receiving placebo magnets, but
      were more likely to correctly identify their treatment (P <.05). CONCLUSION: SMF
      therapy significantly improves disability and may reduce pain when active magnets
      are worn continuously for 4 weeks in patients with CPP, but blinding efficacy is
      compromised.

PMID- 12501068
TI  - A 7.5-MHz finger-grip ultrasound probe for real-time intraoperative guidance
      during complex reproductive surgical procedures.
AB  - OBJECTIVE: A 7.5-MHz finger-grip probe was used to monitor intra-abdominal
      reproductive surgery in two groups of patients. STUDY DESIGN: The first group of
      patients underwent transabdominal myomectomy for multiple uterine leiomyomas (n =
      3) and the second group underwent uterine reconstruction and excision of
      obstructive uterine horn (n = 3). Intraoperative real-time imaging was
      accomplished by direct application of the finger-grip probe to the uterine serosa
      by using saline solution as a transmission media. Ultrasound imaging and surgical
      dissection were carried out both sequentially and simultaneously. RESULTS: In the
      first group of patients, the finger-grip probe provided precise location of the
      leiomyomas and intraoperative guidance for dissection during the myomectomy. In
      the second group of patients, the finger probe provided images of intrauterine
      anatomy in one patient who had a normal-sized and normal-shaped uterus with an
      obstructed intracavitary horn and hematometrium. In two other patients, the
      obstructed uterine horn extended deep into the pelvis lateral to the vagina. Real
      time imaging provided intraoperative monitoring of depth of dissection into the
      paravaginal space. CONCLUSION: The finger-grip probe demonstrated intrauterine
      anatomy and enabled a more directed surgical approach, both in placement of
      uterine incisions for surgical reconstruction and excision of obstructed horns
      for mullerian abnormalities and in identification and dissection for leiomyomas.

PMID- 12501069
TI  - Three-dimensional computed tomography evaluation of bony birth canal morphologic
      deformity (small pelvic cavity) after dome pelvic osteotomy for developmental
      dysplasia of the hip.
AB  - OBJECTIVE: Using three-dimensional computed tomography, we investigated the
      morphologic deformity of the birth canal in patients with developmental dysplasia
      of the hip who underwent dome pelvic osteotomy. STUDY DESIGN: Thirty-five normal
      subjects, 34 patients with developmental dysplasia of the hip who did not undergo
      dome pelvic osteotomy, and 21 patients with developmental dysplasia of the hip
      who underwent dome pelvic osteotomy were recruited for the study. We assessed the
      underlying pelvic deformities together with the postoperative pelvic morphologic
      changes (iatrogenic deformity). RESULTS: Sagittal diameters of the pelvic
      contraction were longer, and transverse diameters of the pelvic inlet, expansion,
      and contraction were shorter in patients after dome pelvic osteotomy than in
      normal control subjects. CONCLUSION: Anthropoid-type pelvis (a long pelvic inlet
      diameter in the sagittal dimension while the corresponding measurement in the
      transverse dimension is short) was observed in as many as 90.5% of patients with
      developmental dysplasia of the hip after dome pelvic osteotomy.

PMID- 12501070
TI  - Cervical length and funneling at 22 and 27 weeks to predict spontaneous birth
      before 32 weeks in twin pregnancies: a French prospective multicenter study.
AB  - OBJECTIVE: Our aim was to determine the accuracy of cervical length and funneling
      of the internal os in the prediction of the spontaneous very preterm birth of
      twin pregnancies. STUDY DESIGN: In a prospective study at 13 centers, routine
      transvaginal ultrasound scanning was used to examine 251 women with twin
      pregnancies at 22 weeks of gestation and 215 women at 27 weeks of gestation;
      cervical length, spontaneous cervical funneling, and funneling after transfundal
      pressure were evaluated. Receiver operating characteristic curve analysis was
      used to determine the best cervical length for the prediction of spontaneous
      preterm birth before 32 and 35 weeks of gestation. We calculated the sensitivity,
      specificity, and predictive values for cervical length and for funneling.
      RESULTS: The median gestational age at delivery was 36 weeks in both populations.
      Of the population that was included at 22 weeks of gestation, 5.2% (13 women)
      gave birth spontaneously before 32 weeks of gestation, and 13.2% (33 women) gave
      birth spontaneously before 35 weeks of gestation; the median cervical length was
      40 mm. The receiver operating characteristic curve showed no clear best cutoff
      point for cervical length. For spontaneous delivery before 32 and 35 weeks of
      gestation, the sensitivity of cervical length < or =30 mm was 46% and 27%,
      respectively; the specificity was 89% and 90%, respectively. The sensitivity of
      funneling was 54% and 33%, and its specificity 89% and 91%, respectively. After
      multivariate analysis, only funneling remained significant for delivery before
      both 32 and 35 weeks of gestation. Of the population that was included at 27
      weeks, 3.3% (7 women) gave birth spontaneously before 32 weeks of gestation, and
      12.4% (26 women) gave birth spontaneously before 35 weeks of gestation; the
      median cervical length was 35 mm. The receiver operating characteristic curve
      showed 25 mm to be the best cutoff point for cervical length. For spontaneous
      delivery before 32 and 35 weeks of gestation, the sensitivity of cervical length
      < or =25 mm was 100% and 54%, respectively, and the specificity was 84% and 87%,
      respectively. The sensitivity of funneling was 86% and 54%, and the specificity
      78% and 82%, respectively. After multivariate analysis, both indicators remained
      significant for delivery before 35 weeks of gestation. Funneling after
      transfundal pressure at 22 or 27 weeks did not predict very preterm delivery.
      CONCLUSION: Cervical length and funneling both predict the very preterm birth of
      twins. Although cervical length is the predictor of choice at 27 weeks of
      gestation, at 22 weeks of gestation the diagnostic values of both parameters are
      close.

PMID- 12501071
TI  - Male predominance in fetal distress during labor.
AB  - OBJECTIVE: The purpose of this study was to assess the association between fetal
      sex and the occurrence of fetal distress during labor. STUDY DESIGN: This was a
      prospective cohort study that incorporated data about 423,033 singleton
      pregnancies from the national perinatal database for secondary obstetric care in
      The Netherlands. All singleton pregnancies on record that were delivered under
      the responsibility of obstetricians in The Netherlands between January 1, 1990,
      and December 31, 1994, were analyzed. Data about fetal sex, gestational age at
      delivery, birth weight, fetal distress during labor, mode of delivery, signs of
      asphyxia at birth, and perinatal death were collected. The associations between
      sex and the occurrence of operative delivery for fetal distress, low 5-minute
      Apgar score (score, 0-3), and perinatal death were evaluated by logistic
      regression analysis. RESULTS: Male fetuses are at increased risk for fetal
      distress during labor, for low Apgar scores, and for perinatal death. After
      adjustment for fetal birth weight and gestational age at delivery, the odds
      ratios were 1.48, 1.27, and 1.27, respectively. All three associations were
      highly statistically significant (P <.0001). CONCLUSION: Male fetuses are at
      increased risk during labor and delivery.

PMID- 12501072
TI  - Endothelial dysfunction in uterine circulation in preeclampsia: can estrogens
      improve it?
AB  - OBJECTIVE: The purpose of this study was to evaluate whether a 3-hour incubation
      with 17beta-estradiol will enhance blood flow- and bradykinin-mediated dilatation
      and alter pressure-induced basal tone in myometrial resistance arteries from
      women with preeclampsia and to evaluate the role of nitric oxide in the responses
      that were observed. STUDY DESIGN: Blood flow- and bradykinin-mediated dilatation
      and responses to intraluminal pressure of 60 and 80 mm Hg were compared before
      and after 3 hours of incubation with 17beta-estradiol (10(-8) mol/L) in isolated
      myometrial arteries with the pressure myography technique. In separate
      experiments, the role of nitric oxide on 17beta-estradiol-induced responses was
      evaluated in the presence of the nitric oxide synthase inhibitor (10(-4) mol/L).
      Endothelial morphologic condition was evaluated by scanning electron microscopy.
      RESULTS: Incubation with 17beta-estradiol significantly improved blood flow
      mediated dilatation compared with initial blood flow-mediated response in
      arteries from women with preeclampsia. This effect was nitric oxide mediated,
      because the nitric oxide synthase inhibitor abolished the response. Arteries from
      women with preeclampsia demonstrated impaired bradykinin-mediated dilatation
      compared with that obtained in arteries from normal pregnant women. The 17beta
      estradiol had no effect on bradykinin-mediated dilatation in arteries from women
      with preeclampsia. The enhanced pressure-induced tone at 80 mm Hg compared with
      the tone that developed at 60 mm Hg in arteries from women with preeclampsia was
      reduced after incubation with 17beta-estradiol. This reduction was also nitric
      oxide mediated. Morphologic signs of endothelial dysfunction were evident in
      arteries from women with preeclampsia. CONCLUSION: The 17beta-estradiol improved
      impaired blood flow-mediated dilatation and reduced basal tone through a nitric
      oxide-mediated pathway in isolated myometrial arteries from women with
      preeclampsia.

PMID- 12501073
TI  - Fetal hepatic calcifications: prenatal diagnosis and outcome.
AB  - OBJECTIVE: The purpose of this study was to provide information on the causes and
      postnatal outcomes of fetal liver calcifications that were detected by ultrasound
      imaging. STUDY DESIGN: Cases with fetal liver calcifications that were
      encountered between 1992 and 2001 were evaluated. A detailed fetal ultrasound
      imaging for associated abnormalities, maternal STORCH (syphilis, cytomegalovirus,
      herpesvirus 1 and 2, rubella, and Toxoplasma ) analysis, parvovirus serologic
      condition, and parental cystic fibrosis mutations analysis were performed;
      amniocentesis was offered in all cases. All infants who were born alive were
      examined and followed up. RESULTS: Sixty-one pregnant women with fetal liver
      calcifications were identified. Forty of 61 patients had additional fetal
      abnormalities; 21 of 61 cases of fetal liver calcifications were isolated; 11/61
      patients (18%) had abnormal karyotypes (trisomy 13, 4 patients; trisomy 21, 2
      patients; trisomy 18, 1 patient; monosomy X (45,X), 1 patient; 4p-, 22q+, and
      8p+, 1 patient). Ten of 11 patients with abnormal karyotypes had other
      abnormalities that were found on ultrasound imaging. Two patients had
      intrauterine infection, one patient had cytomegalovirus, and one patient had
      parvovirus B19 infection. Eighteen of 40 patients underwent pregnancy
      termination, one fetus died in utero, one newborn infant died, and two infants
      had neurologic sequelae. Of 21 patients with isolated liver calcifications, one
      fetus had parvovirus B19 infection and one infant had trisomy 21. The remainder
      of the infants each had a good outcome. CONCLUSION: Fetal liver calcifications
      are relatively common. Isolated cases have a good prognosis after aneuploidy and
      infection have been ruled out. However, additional major abnormalities present a
      risk for chromosomal abnormalities, mainly trisomy 13.

PMID- 12501074
TI  - Aspirin consumption during the first trimester of pregnancy and congenital
      anomalies: a meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to determine, on the basis of published
      reports, whether aspirin use during the first trimester of pregnancy is
      associated with an increased risk of congenital malformations. STUDY DESIGN: We
      reviewed the literature for published studies that reported exposure to aspirin
      during the first trimester of pregnancy and congenital malformations. Two
      reviewers independently determined whether a study should be included in the
      final analysis and extracted the data. We calculated the pooled odds ratio and
      95% CI. RESULTS: Twenty-two studies met the inclusion criteria. In the eight
      studies that reported an overall risk, the risk of congenital malformations in
      offspring of women who were exposed to aspirin was not significantly higher than
      that in control subjects (odds ratio, 1.33; 95% CI, 0.94-1.89). However, a
      significantly increased risk of gastroschisis (odds ratio, 2.37; 95% CI, 1.44
      3.88) was found. CONCLUSION: We found no evidence of an overall increase in the
      risk of congenital malformations that could be associated with aspirin. Aspirin
      exposure during the first trimester may be associated with an increased risk of
      gastroschisis.

PMID- 12501075
TI  - The T-helper 1/T-helper 2 balance in peripheral blood of women with hyperemesis
      gravidarum.
AB  - OBJECTIVE: The purpose of this study was to evaluate the T-helper 1/T-helper 2
      balance and its relation with pregnancy-related hormones in hyperemesis
      gravidarum. STUDY DESIGN: The T-helper 1/T-helper 2 ratio and plasma progesterone
      and estrogen levels were examined in the peripheral blood of 22 women with
      hyperemesis gravidarum and normal pregnancies. The proportion of CD4-positive
      cells that expressed intracellular cytokines (interferon gamma and interleukin-4)
      were analyzed by blood flow cytometry. The ratio of interferon gamma-secreting
      cells to interleukin-4-secreting cells was taken as the T-helper 1/T-helper 2
      ratio. RESULTS: In hyperemesis gravidarum, the proportions of interleukin-4
      secreting cells increased, and the T-helper 1/T-helper 2 ratio averaged 8.4 +/-
      0.9, which was significantly lower than in normal pregnancy (11.6 +/- 1.1, P
      <.05). The changes in the T-helper 1/T-helper 2 ratio in hyperemesis gravidarum
      were accompanied by the elevation of progesterone and estrogen levels.
      CONCLUSION: A further shift of the T-helper 1/T-helper 2 balance to the T-helper
      2 dominance in hyperemesis gravidarum may be related to the increase of
      progesterone and estrogen levels.

PMID- 12501076
TI  - Hemodynamic changes and baroreflex gain in the supine hypotensive syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine whether supine hypotensive
      syndrome is caused by a decreased baroreflex gain that results in inadequate
      compensatory responses to restore cardiac output. STUDY DESIGN: Ten third
      trimester gravid women with symptoms that were suggestive of supine hypotensive
      syndrome and 10 control subjects without symptoms were studied. Patients were
      studied initially for 30 minutes in the lateral recumbent position with
      continuous heart rate, blood pressure, external cardiotocography, and cardiac
      output determinations every 5 minutes. After 30 minutes, the patient was
      repositioned supine for up to an additional 30 minutes, and all measurements were
      repeated similarly. This lateral-supine sequence was repeated twice or until
      symptoms precluded further testing. RESULTS: The two groups were demographically
      similar. With maternal position change to supine, cardiac output (-2.7 L/min vs 
      1.0 L/min, P =.04) and mean arterial blood pressure (-10.7 mm Hg vs -2.5 mm Hg, P
      =.03) were respectively lower, and heart rate (+26.9 vs +14.4 beats/min, P =.04)
      was higher in the subjects with supine hypotensive syndrome than in the control
      subjects. Baroreflex gain, however, did not differ between the subjects with
      supine hypotensive syndrome and control subjects (P =.26). CONCLUSION: We were
      unable to demonstrate a decrease in baroreflex gain as a possible cause of supine
      hypotensive syndrome. Inadequate pelvic collateral circulation that leads to a
      greater decrease in cardiac output may be causative in the syndrome.

PMID- 12501077
TI  - Optimization of informed consent for umbilical cord blood banking.
AB  - OBJECTIVE: The purpose of this project was to evaluate the informed consent
      process for donation to a public umbilical cord blood bank. STUDY DESIGN:
      Telephone interviews were conducted with 170 women who had given consent to
      donate their newborn infants' umbilical cord blood. RESULTS: Of the 170 women who
      were contacted, 96.8% of the women reported that all their questions had been
      answered. Nevertheless, approximately one third of the respondents did not
      consider themselves to be in research, and almost one quarter of the respondents
      did not know how to contact the umbilical cord blood bank if they or their infant
      became seriously ill. Further, a substantial proportion of the respondents did
      not understand the full range of alternatives to donation and incorrectly
      endorsed potential benefits. CONCLUSION: Informed consent could be optimized by
      (1) having those personnel who obtain consent emphasize that banking involves
      research and to explain the true benefits of donation, (2) ensuring that parents
      know how and when to contact the umbilical cord blood bank after donation, and
      (3) using phone surveys to continue assessments and to monitor changes in the
      process.

PMID- 12501078
TI  - Structural remodeling of rat uterine veins in pregnancy.
AB  - OBJECTIVE: This study characterized the cellular remodeling that contributes to
      uterine venous growth during gestation and evaluated the effect of pregnancy on
      the mechanical properties of the uterine vein. STUDY DESIGN: Diameter and
      distensibility were calculated in pressurized uterine veins from virgin and
      pregnant (19-20 days of gestation) rats; the rates of cellular division
      (endothelial, vascular smooth muscle) were quantified with an intraperitoneal
      bromodeoxyuridine injection and immunohistochemistry. Elastin content, adrenergic
      nerve density, and wall thickness were determined in fixed uterine veins and
      quantified with an imaging program. RESULTS: There was a statistically
      significant increase in the diameter and mitotic indices (endothelial, vascular
      smooth muscle) in uterine veins from late pregnant versus nonpregnant animals.
      Adrenergic nerve density was diminished significantly during gestation. Venous
      distensibility increased during pregnancy, with an associated reduction in
      elastin content. CONCLUSION: Pregnancy results in coordinated and multifaceted
      structural remodeling of uterine veins with subsequent changes in caliber,
      mechanical properties, rates of cellular division, adrenergic innervation, and
      matrix composition.

PMID- 12501079
TI  - Venoarterial communication as a mechanism for localized signaling in the rat
      uterine circulation.
AB  - OBJECTIVE: Venoarterial communication describes the phenomenon whereby molecular
      signals in a vein directly influence an adjacent artery. The objective of this
      study was to investigate, in vitro, the existence of such a pathway in the
      uterine circulation of the rat. STUDY DESIGN: Paired uterine vessels from late
      pregnant and virgin rats were pressurized and studied in a dual-perfusion
      vasograph. Veins were perfused with phenylephrine and endothelin-1, alone or in
      combination, and the vasoactive responses of both vessels were recorded. RESULTS:
      Venous perfusion of phenylephrine resulted in concentration-dependent arterial,
      but not venous, constriction. Conversely, veins, but not arteries, demonstrated
      concentration-dependent constriction to intravenous endothelin-1. Superfusion of
      endothelin-1 constricted both vessels. Coperfusion of endothelin-1 and
      phenylephrine constricted the veins and attenuated the previously observed
      arterial response to intravenous phenylephrine. CONCLUSION: The results of this
      study support the existence of venoarterial communication within the uterine
      circulation through an endothelin-1-sensitive pathway.

PMID- 12501080
TI  - Comparison of pregnancy dating by last menstrual period, ultrasound scanning, and
      their combination.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of algorithms
      for the assignment of gestational age with the use of the last menstrual period
      and early ultrasound information. STUDY DESIGN: Gestational age estimates that
      are based on last menstrual period, ultrasound scanning, or their combination
      were compared among women who attended prenatal care clinics in central North
      Carolina (n = 3655) by an evaluation of digit preference in the last menstrual
      period dates and a comparison of mean gestational age, preterm and postterm
      categories with the use of kappa statistics, difference between actual and
      expected delivery date, and birth weight among subgroups with discrepant
      assignments. RESULTS: Last menstrual period reports show digit preference, assign
      gestation 2.8 days longer on average than ultrasound scanning, yield
      substantially more postterm births (12.1% vs 3.4%), and predict delivery among
      term births less accurately. Misclassification of births as postterm was more
      common in younger women, those of nonoptimal prepregnancy body weight, cigarette
      smokers, and women who reported last menstrual period using preferred dates of
      the month. CONCLUSION: Last menstrual period estimates of the duration of
      gestation are subject to both random error and a systematic tendency to overstate
      the duration of gestation, most likely because of delayed ovulation.

PMID- 12501081
TI  - Transcranial doppler measurement of cerebral velocity indices as a predictor of
      preeclampsia.
AB  - OBJECTIVE: We have previously shown that women with preeclampsia demonstrate
      cerebral hyperperfusion and abnormal cerebrovascular autoregulation. In the
      current study, we tested the hypothesis that abnormal cerebrovascular function
      can be detected before the clinical onset of preeclampsia. STUDY DESIGN:
      Transcranial Doppler ultrasonography was performed for 166 women in the second
      trimester of pregnancy to measure peak, end-diastolic, and mean velocities in the
      middle cerebral arteries. Preeclampsia developed in 10 patients who were
      initially normotensive. In a nested case-controlled design, each patient with
      preeclampsia who was initially normotensive was matched for gestational age at
      the time of initial examination, maternal age, and parity with two pregnant women
      who remained normotensive and who were delivered at term. All measurements were
      performed with the subject in the left lateral position at baseline, during 5%
      carbon dioxide inhalation, and during a 2-minute isometric handgrip test. Blood
      pressure, heart rate, oxygen saturation, and end-tidal PCO (2) were recorded with
      each Doppler measurement. The mean pulsatility index, resistance index, and
      cerebral perfusion pressure at each time were calculated and compared.
      Statistical significance was set at a probability value of <.05. RESULTS: The
      studies were performed at 19 to 28 weeks of gestation. Preeclampsia developed an
      average of 13.6 +/- 1.0 weeks after the study. Baseline mean blood pressure and
      heart rate were similar, but middle cerebral arteries pulsatility and resistance
      indices were lower in the women with preeclampsia who were initially normotensive
      compared with the pregnant women who were normotensive (0.83 and 0.54 vs 0.73 and
      0.50, respectively; P <.05). Both maneuvers caused a significant reduction in the
      pulsatility and resistance indices. With the use of baseline values as
      covariates, no significant differences were noted in the response to either
      carbon dioxide inhalation or handgrip between the group of women who remained
      normotensive and the group of women with preeclampsia who were initially
      normotensive. CONCLUSION: Normotensive pregnant women who later have preeclampsia
      demonstrate lower baseline pulsatility and resistance indices but normal
      vasodilatory responses to challenge tests. These findings suggest that women who
      are destined to have preeclampsia experience cerebral hemodynamic changes that
      predate the development of overt preeclampsia symptoms.

PMID- 12501082
TI  - A history of induced abortion in relation to substance use during subsequent
      pregnancies carried to term.
AB  - OBJECTIVE: Previous research has revealed a general association between induced
      abortion and substance use. The purpose of this study was to examine the
      correlation when substance use is measured specifically during a subsequent
      pregnancy. STUDY DESIGN: A nationally representative sample of women was surveyed
      about substance use during pregnancy shortly after giving birth. Women with a
      previous induced abortion, whose second pregnancy was delivered, were compared
      separately with women with one previous birth and with women with no previous
      births. RESULTS: Compared with women who gave birth, women who had had an induced
      abortion were significantly more likely to use marijuana (odds ratio, 10.29; 95%
      CI, 3.47-30.56), various illicit drugs (odds ratio, 5.60; 95% CI, 2.39-13.10),
      and alcohol (odds ratio, 2.22; 95% CI, 1.31-3.76) during their next pregnancy.
      The results with only first-time mothers were very similar. CONCLUSION:
      Psychosocial mechanisms that may explain the findings are discussed. Screening
      for abortion history may help to identify pregnant women who are at risk for
      substance use more effectively.

PMID- 12501083
TI  - Collagen messenger RNA expression in the human amniochorion in premature rupture
      of membranes.
AB  - OBJECTIVE: It has been suggested that there is a decrease in the collagen content
      of the fetal membranes when there is premature rupture of the membranes before
      the onset of labor. This study was designed to determine whether decreased
      amniochorion collagen production (as measured by reduced amounts of messenger
      RNA) or alterations in relative production of different fibrillar and
      nonfibrillar collagens are associated with premature rupture of the membranes.
      STUDY DESIGN: Fetal membranes were collected after preterm (24-36 weeks of
      gestation) and term (> or =37 weeks of gestation) deliveries both with and
      without premature rupture of the membranes. Specimens with evidence of histologic
      chorioamnionitis were excluded. The messenger RNA levels for fibrillar collagen
      types I, III, and V and fibril-associated collagens with interrupted triple
      helices types XII and XIV were measured with relative quantitative reverse
      transcriptase-polymerase chain reaction. RESULTS: The messenger RNA levels for
      fibrillar collagens decreased with advancing gestational age. Preterm premature
      rupture of membranes was associated with increased messenger RNA levels for
      fibrillar collagens and fibril-associated collagens with interrupted triple
      helices collagen XII, but not type XIV. The greatest change in relative amounts
      of collagen messsenger RNA was demonstrated by an increased type I/XIV ratio,
      which was due to the up-regulation of type I levels, but not type XIV levels.
      CONCLUSION: A rise in fibrillar collagen production (messenger RNA) for types I,
      III, and V and fibril-associated collagens with interrupted triple-helices
      collagen type XII is observed with preterm premature rupture of the membranes.
      There is no evidence for a similar up-regulation of messenger RNA for fibril
      associated collagens with interrupted triple-helices collagen type XIV. The rise
      in the collagen I/XIV messenger RNA ratio in preterm premature rupture of the
      membranes may result in collagen fibrils without enough stabilizing fibril
      associated collagens with interrupted triple-helices type XIV on the fibril
      surface to maintain structural integrity.

PMID- 12501084
TI  - Isolated microparticles, but not whole plasma, from women with preeclampsia
      impair endothelium-dependent relaxation in isolated myometrial arteries from
      healthy pregnant women.
AB  - OBJECTIVE: This study was performed to establish whether microparticles from
      plasma of women with preeclampsia cause endothelial dysfunction, as described for
      isolated myometrial arteries in preeclampsia. STUDY DESIGN: Myometrial arteries
      were isolated from biopsy specimens obtained at cesarean delivery from healthy
      pregnant women (n = 22) and mounted in a wire myograph. Bradykinin concentration
      response curves were obtained before and after 1-hour incubation or after
      overnight incubation with one of the following preparations of plasma from
      individual women with preeclampsia (n = 16): Whole plasma, microparticle-free
      plasma, isolated microparticles resuspended in physiologic saline solution or
      physiologic saline solution. Overnight incubation was also performed with
      microparticles isolated from healthy pregnant women (n = 6). One-hour incubation
      was performed with 2% or 10% solution and overnight incubation with 5% solution.
      RESULTS: No effect of preeclamptic plasma, with or without microparticles, on
      bradykinin-mediated relaxation was observed. Overnight, but not 1-hour,
      incubation with preeclamptic microparticles caused abolishment of bradykinin
      mediated relaxation in contrast to healthy pregnant microparticles (P <.005).
      CONCLUSION: Preeclamptic microparticles, but not healthy pregnant microparticles
      cause endothelial dysfunction in isolated myometrial arteries from healthy
      pregnant women after overnight incubation, whereas other preeclamptic plasma
      constituents protect the endothelium from this effect.

PMID- 12501085
TI  - Mode of delivery and outcome of 699 term singleton breech deliveries at a single
      center.
AB  - OBJECTIVE: Elective cesarean delivery has been postulated to improve the outcome
      of term fetuses in breech presentation. We retrospectively compared the short-
      and long-term outcomes of term infants who were delivered from a breech
      presentation at a single center. STUDY DESIGN: We reviewed 699 consecutive term
      breech presentations according to the intended mode of delivery at a single
      center between January 1993 and December 1999. The short-term outcome measures
      were perinatal death, neonatal death, or serious neonatal morbidity; the long
      term outcome measures were developmental delay and spasticity. RESULTS: The rate
      of serious perinatal morbidity in the trial-of-labor and cesarean delivery groups
      was 2.3% and 0.5%, respectively (P =.12). There was no perinatal or neonatal
      death in either group. With a median follow-up period of 57 months (range, 13-100
      months), the rate of developmental delay was 1.9% and 0.5%, respectively (P
      =.29). Spasticity was not noted in any of the children. CONCLUSION: Our data
      suggest that planned vaginal delivery remains an option for selected term breech
      presentations.

PMID- 12501086
TI  - Mechanisms of action of intrauterine devices: update and estimation of
      postfertilization effects.
AB  - There are many potential mechanisms of action for the intrauterine device (IUD),
      which vary by type of IUD (inert, copper, or hormonal). This paper reviews the
      evidence for each potential mechanism of action. On the basis of available data
      for fertilization rates and clinical pregnancy rates, the relative contribution
      of mechanisms acting before or after fertilization were quantitatively estimated.
      These estimates indicate that, although prefertilization effects are more
      prominent for the copper IUD, both prefertilization and postfertilization
      mechanisms of action contribute significantly to the effectiveness of all types
      of intrauterine devices.

PMID- 12501087
TI  - Endometrioma of the abdominal wall.
AB  - We describe a case of a large endometrioma in an abdominal scar and the approach
      to evaluation and therapy.

PMID- 12501088
TI  - Calcium channel blocker, nimodipine, for the treatment of bipolar disorder during
      pregnancy.
AB  - Bipolar disorder in pregnancy was treated with nimodipine, because of lithium
      induced nephrogenic diabetes insipidus. A 33-year-old primigravida woman at
      approximately 22 weeks 6 days of gestation had increasing blood pressure since 16
      weeks of gestation, despite methyldopa 500 mg twice daily. She also had
      hypothyroidism and bipolar disorder, which were treated with levothyroxine and
      lithium carbonate, respectively. Nephrogenic diabetes insipidus developed,
      presumably because of chronic lithium exposure in high doses. She did not
      tolerate carbamazepine (the other agent commonly used for bipolar disorder in
      pregnancy). Thus, nimodipine was tried and tolerated well; furthermore, it was
      very effective in controlling her bipolar disorder. Nimodipine successfully
      controlled the bipolar disorder of a woman during pregnancy, who was intolerant
      of more commonly used agents.

PMID- 12501089
TI  - Intrapericardial extralobar pulmonary sequestration-ultrasound and magnetic
      resonance prenatal diagnosis.
AB  - Extralobar pulmonary sequestrations are usually thoracic or abdominal lesions. A
      29-week fetus demonstrated a 3.1 x 2.1 x 2.3 cm intrapericardial mass on
      ultrasonography. Magnetic resonance imaging demonstrated an extracardiac origin
      and suggested a pulmonary sequestration, which was confirmed after successful
      postnatal resection. Extralobar pulmonary sequestration should be considered in
      the presence of a fetal intrapericardial mass.

PMID- 12501090
TI  - Lymphocytic choriomeningitis virus: emerging fetal teratogen.
AB  - Lymphocytic choriomeningitis virus (LCMV), a rodent-borne arenavirus, is an often
      undiagnosed human fetal teratogen. We describe a neonate born with hydrocephalus
      and chorioretinitis after maternal second-trimester symptomatic LCMV infection.
      Previously reported affected infants are reviewed. We strongly suggest that
      obstetricians counsel their pregnant patients regarding the potential hazard that
      contact with infected pet, laboratory, and household mice and hamsters poses to
      pregnant women and their unborn children.

PMID- 12501091
TI  - Completely aborted uterine leiomyosarcoma in the puerperium.
AB  - A patient passed a large tissue mass at home on postpartum day 1. Pathologic
      examination demonstrated leiomyosarcoma. A total abdominal hysterectomy was
      performed, which demonstrated residual disease. All tissue passed in the
      puerperium should be evaluated to ensure that significant pathologic conditions
      are not overlooked. Conservative management of leiomyosarcomas is controversial.

PMID- 12501092
TI  - Troponin I in the diagnosis of acute myocardial infarction in pregnancy, labor,
      and post partum.
AB  - Cardiac troponin I has become the marker of choice for the diagnosis of acute
      myocardial infarction. There are specific characteristics of this test that makes
      it desirable for the diagnosis of acute myocardial infarction in pregnancy,
      labor, and post partum.

PMID- 12501093
TI  - Fetal lung maturity indices-a plea for gestational age-specific interpretation: a
      case report and discussion.
AB  - A fetus with mature amniotic fluid lung indices was delivered with subsequent
      respiratory distress syndrome, demonstrating that fetal pulmonary maturity needs
      to be viewed as a probability. We calculated the probability of respiratory
      distress as a function of gestational age and fetal lung maturity. The percent
      risks are displayed in an easily readable table format.

PMID- 12501094
TI  - Sigmoid endometriosis in a postmenopausal woman.
AB  - Bowel obstruction resulting from endometriosis is an infrequently observed
      phenomenon in postmenopausal women. A 69-year-old woman without hormone
      replacement had clinical and radiologic findings consistent with a pelvic tumor
      invasive into the wall of the sigmoid colon. The patient underwent resection of
      the sigmoid colon and total hysterectomy. Histologic examination revealed
      endometrioma. This case documents the possible occurrence of symptomatic bowel
      endometriosis after years of a hormonally castrated state.

PMID- 12501095
TI  - Vesicouterine fistula after uterine artery embolization: a case report.
AB  - Complications of uterine artery embolization (UAE) for treatment of leiomyoma
      uteri include contrast reactions, hematoma, postembolization syndrome, infection,
      pulmonary embolus, premature ovarian failure, and uterine necrosis. We present a
      case of vesicouterine fistula and extrusion of a degenerating leiomyoma into the
      bladder after UAE, necessitating hysterectomy and partial cystectomy for repair.

PMID- 12501096
TI  - Five-year experience with midtrimester amniocentesis performed by a single group
      of obstetriciangynecologists at a community hospital.

PMID- 12501097
TI  - Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine
      conservation and subsequent pregnancy in the treatment of early invasive cervical
      cancer.

PMID- 12501099
TI  - Pericranial flap for closure of paramedian anterior skull base defects.
AB  - OBJECTIVE: We sought to examine the position of a pericranial flap reconstruction
      of anterior skull base defects with respect to the original floor of the anterior
      cranial fossa. STUDY DESIGN: A retrospective chart and radiology review of 17
      patients (1993-2001) with pericranial flap reconstruction for anterior skull base
      defects and 17 controls was performed. RESULTS: At 6 or more months after
      surgery, the new positions of the pericranial flaps ranged from 5 mm above to
      11.3 mm below the positions of the original cribriform plates. There were no
      complications related to the pericranial flaps such as hemorrhage, flap loss, or
      brain herniation except for 2 (11.8%) cerebrospinal fluid leaks, 1 of which
      required operative correction. CONCLUSION: Pericranial flap reconstruction is a
      reliable method with low morbidity for closure of the most common skull base
      defect from the craniofacial resection that entails removal-unilateral or
      bilateral-of the fovea ethmoidalis, cribriform plate, and/or superior septum.
      This flap creates a watertight seal between the extradural space and the nasal
      cavity, prevents clinically significant brain herniation, and is associated with
      a low rate of cerebrospinal fluid leakage even without postoperative lumbar
      subarachnoid drainage of the cerebrospinal fluid.

PMID- 12501100
TI  - Cough and paradoxical vocal fold motion.
AB  - OBJECTIVES: The differential diagnosis and treatment of patients with chronic
      cough, paradoxical vocal fold motion, and disordered breathing can be a challenge
      to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis,
      and tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and
      rhinologic (ie, allergies and rhinosinusitis) etiologies are commonly diagnosed
      and treated effectively. However, occasionally one is faced with patients who are
      refractory to medical treatment and have no obvious rhinologic, laryngeal or
      pulmonary cause. STUDY DESIGN AND SETTING: We conducted a review of the
      literature. METHODS: We present a thorough review of the current medical
      literature exploring the complex neurologic mechanisms involved in the production
      of cough and the relationship between gastroesophageal reflux disease, vagal
      neurapathy, and paradoxical vocal fold motion. RESULTS: The diagnosis and
      successful treatment of chronic cough can be complex. It requires a thorough
      understanding of the neurologic mechanisms behind cough excitation and
      suppression. Successful treatment strategies include aggressive management of the
      patient's reactive airway disease, gastroesophageal reflux disease, and, in
      select cases, paradoxical vocal fold motion. This may involve a well-coordinated
      effort among pulmonologists, otolaryngologists, gastroenterologists, and speech
      pathologists. CONCLUSION: Gastroesophageal reflux disease, vagal neuropathy, and
      paradoxical vocal fold motion are additional causes of chronic cough and
      disordered breathing that need to be considered, in the absence of obvious
      laryngotracheal and/or rhinologic pathology. A high index of suspicion is
      essential in making the diagnosis and formulating an effective multidisciplinary
      treatment plan for these patients.

PMID- 12501101
TI  - Cysteinyl leukotrienes in chronic hyperplastic rhinosinusitis.
AB  - OBJECTIVES: Our study was designed to demonstrate that, similar to asthma,
      eosinophilic chronic rhinosinusitis is a disease characterized by activation and
      the expression of cysteinyl leukotrienes (LTs). METHODS: Nasal polyp tissue was
      evaluated from 28 consecutive individuals undergoing elective polypectomy in whom
      neutrophils were not present on pathologic examination. Tissue was analyzed for
      pathosis with particular attention to the presence of eosinophils. Patients with
      moderate to high levels of mucosal eosinophils were classified as having
      eosinophilic rhinosinusitis (ECRS). Those with few or absent mucosal eosinophils
      were classified as having noneosinophilic rhinosinusitis (NECRS). Cysteinyl LTs
      were quantified by a sensitive competitive enzyme immunoassay, and the levels of
      cysteinyl LTs were compared in the groups. RESULTS: There were 20 patients with
      ECRS and 8 patients with NECRS. Cysteinyl LTs were identified in polyp tissue
      from 24 of 28 subjects and were >5 pg/gm tissue in 15 of 28. The average level of
      LTC(4) in patients with few mucosal eosinophils was 38.3 pg/g. The average amount
      in those with moderate to large amounts of mucosal eosinophils was 36.7 pg/g.
      There was no significant difference between the 2 groups. CONCLUSION: ECRS and
      NECRS can be considered diseases of excessive expression of cysteinyl LTs. LT
      expression occurs in patients who demonstrate few or no mucosal eosinophils,
      which indicates that cell lines other than eosinophils may be responsible for LT
      production in chronic rhinosinusitis.

PMID- 12501102
TI  - A comparison of screening methods in school-aged children.
AB  - OBJECTIVE: We sought to compare the findings of 3 different hearing screening
      methods in school-aged children. STUDY DESIGN AND SETTING: Prospective testing of
      second- and third-grade students in their schools was carried out. METHODS: Three
      hundred children (599 ears) were screened by using 3 test modalities, pure-tone
      audiometry, distortion product otoacoustic emissions (DPOAE), and tympanometry.
      RESULTS: All of the tests were normal in 532 ears (89%), and all were abnormal in
      12 ears (2%). Tympanometry yielded the most abnormalities (8.3%), and pure-tone
      testing demonstrated the fewest (3.3%), with a positive rate of 6.3% for DPOAE
      testing. False-positive rates were 1.2%, 4.2%, and 6.4% for pure tones, DPOAE,
      and tympanometry, respectively, when normal results on pure-tones or DPOAE were
      taken to represent true hearing. CONCLUSION/SIGNIFICANCE: We continue to
      recommend pure-tone testing as an effective screening method, with follow-up by
      using otoacoustic emissions in those who fail the pure-tone test.

PMID- 12501103
TI  - Biomechanical influences of magnetic resonance imaging on the SOUNDTEC Direct
      System implant.
AB  - OBJECTIVE: The purpose of this study was to measure the forces experienced by the
      SOUNDTEC Direct System magnetic implant during 0.3-T MRI. STUDY DESIGN: Torsional
      and linear forces imposed on 8 implants were measured by using calibrated
      neurologic Von Frey hairs and were compared with finite-element analysis
      predictions and the forces required to separate the incudostapedial joints of
      unpreserved temporal bones. An implanted embalmed autopsy specimen was also
      examined before and after 1.5-T MRI. RESULTS: Peak linear force at the orifice of
      the MRI core measured 0.51g (+/-0.2 SD). Maximum torque occurred at the MRI core
      center and measured 11.4g-cm (+/-1.2 SD). The mean torque required to separate
      the incudostapedial joints of 12 unpreserved temporal bones was 33.8g-cm (+/-20.4
      SD). The autopsy specimen sustained a 1.5-T MRI scan without disruption of the
      ossicular chain or explantation. CONCLUSIONS: Physical and mechanical testing of
      the SOUNDTEC implant indicates that the structural integrity of the ossicles will
      be maintained during 0.3-T MRI of the human head.

PMID- 12501104
TI  - Incidence of complications for subtotal ionized field ablation of the tonsils.
AB  - OBJECTIVE: Ionized field ablation, or coblation-assisted subtotal tonsillectomy,
      has been described as a new alternative technique for the management of tonsillar
      disease. This study was designed to review the incidence of complications in
      patients undergoing this procedure. STUDY DESIGN: A 10-surgeon retrospective
      chart review of the intraoperative and postoperative complications of patients
      undergoing ionized field ablation subtotal removal of tonsils was performed.
      Postoperative pain, dietary restrictions, and activity level were not reviewed.
      RESULTS: Of the 528 patients who underwent ionized field ablation of their
      tonsils, the incidence of intraoperative and postoperative complications compared
      favorably with those reported in retrospective studies in the literature for
      traditional subcapsular tonsillectomy. Significant postoperative bleeding
      occurred in less than 1%, and only 1 patient required surgical control of
      bleeding in the operating room. No patients required transfusions of any blood
      products. CONCLUSIONS: Ionized field ablation subtotal tonsillectomy may offer an
      alternative to traditional subcapsular tonsillar surgery with a decreased
      incidence of postoperative complications. Further study is necessary to establish
      the complication rate of this technique.

PMID- 12501105
TI  - The effect of ankyloglossia on speech in children.
AB  - OBJECTIVE: We wanted to determine whether ankyloglossia is associated with
      articulation problems and the effect of frenuloplasty on speech and tongue
      mobility. STUDY DESIGN: We conducted a prospective study of 30 children aged 1 to
      12 years with ankyloglossia undergoing frenuloplasty. Outcomes were assessed by
      measurements of tongue mobility, speech evaluation, and parent questionnaires.
      RESULTS: Mean tongue protrusion improved from 14.2 mm preoperatively to 25.8 mm
      postoperatively (P < 0.01). Similarly, mean tongue elevation improved from 5.2 to
      22 mm (P < 0.01). Preoperative speech pathology evaluation documented
      articulation problems thought due to ankyloglossia in 15 of 21 children.
      Postoperative evaluation in 15 of these children showed improvement in
      articulation in 9, no change in 4 who had normal speech preoperatively, and an
      ongoing articulation disorder in 2. Parent perception of speech intelligibility
      on a scale of 1 to 5 improved from 3.4 to 4.2 (P < 0.01). CONCLUSION: Tongue
      mobility and speech improve significantly after frenuloplasty in children with
      ankyloglossia who have articulation problems.

PMID- 12501106
TI  - Smoke exposure and outcome of endoscopic sinus surgery in children.
AB  - OBJECTIVE: The study goal was to determine whether cigarette smoke exposure in
      children who are undergoing endoscopic sinus surgery (ESS) for chronic sinusitis
      will have an impact on the outcome. DESIGN: We conducted a cohort study in a
      tertiary care children's hospital setting. PATIENTS AND METHODS: The study
      population consisted of 118 patients who underwent ESS between January 1994 and
      June 1999. The mean age was 6.5 (range, 2 to 13 years). The outcome of ESS was
      measured > or =1 year after the operation. A questionnaire was mailed to the
      caretakers to measure success. Those who required revision subsequently were
      considered as failures. RESULTS: Multivariate logistic regression analysis was
      performed with smoke exposure as an independent variable and outcome measured as
      success of procedure. The overall success rate was 83%. Univariate analysis of
      smoke exposure and outcome of surgery revealed that children exposed to smoke in
      household had a 70% success rate compared with children not exposed to smoke, who
      had a 90% success rate (P = 0.007). Multivariate analysis revealed smoke exposure
      continued to be an independent predictor of success. CONCLUSION: ESS in children
      with cigarette smoke exposure predisposes to a poorer outcome. This needs to be
      taken into consideration when recommending ESS for those children.

PMID- 12501107
TI  - Tele-3-dimensional computer-assisted functional endoscopic sinus surgery: new
      dimension in the surgery of the nose and paranasal sinuses.
AB  - One of the main objectives of our 3-dimensional (3D) computer-assisted functional
      endoscopic sinus surgery was to design a computer-assisted 3D approach to the
      presurgical planning, intraoperative guidance, and postoperative analysis of the
      anatomic regions of the nose and paranasal sinuses. Such an extremely powerful
      approach should allow better insight into the operating field, thereby
      significantly increasing the safety of the procedure. The last step to
      implementing the technology in the operating room was to connect the computer
      workstations and video equipment to remote locations by using a high-speed, wide
      bandwidth computer network. During patient preparation, the surgeon in the
      operating room consulted remote experienced and skillful surgeons by viewing CT
      images and 3D models on computer workstations. The surgeon and consultants used
      software for CT image previews and 3D model manipulations on top of collaboration
      tools to define the pathosis, produce an optimal path to the pathosis, and decide
      how to perform the real surgical procedure. With tele-flythrough or tele-virtual
      endoscopy rendered through the use of 3D models, both surgeons can preview all
      the characteristics of the region (ie, anatomy, pathosis) and so predict and
      determine the next steps of the operation. This ensures greater safety thanks to
      the operation guidance and reduces the possibility of intraoperative error. The
      duration of the teleconsultation is thus shortened, which may prove the greatest
      benefit of tele-3D computer-assisted surgery. If this method were used, clinical
      institutions would spend less money for telesurgical consultation.

PMID- 12501108
TI  - Use of nebulized antibiotics for acute infections in chronic sinusitis.
AB  - OBJECTIVE: Infections in patients with chronic sinusitis after surgery can be
      difficult to treat. Nebulized antimicrobial therapy was studied as a treatment
      option. STUDY DESIGN: Patients with chronic sinusitis, previous sinus surgery,
      and an acute infection were offered nebulized antibiotics or standard therapy.
      Cultures were taken and sensitivity testing was performed. Retrospective chart
      reviews were also performed. RESULTS: Forty-two patients were included. The most
      common side effects were sore throat and cough. Symptomatic and endoscopic data
      before and after nebulized therapy showed a longer infection-free period
      (average, 17 weeks) compared with standard therapy (average, 6 weeks).
      Improvements in posterior nasal discharge, facial pain/pressure, and emotional
      consequences were noted. CONCLUSION: Nebulized therapy was safe and effective in
      this cohort. Endoscopy and outcome measure changes showed consistent
      improvements. SIGNIFICANCE: A novel therapy for acute sinus infections in
      patients with chronic sinusitis and previous endoscopic sinus surgery is
      presented.

PMID- 12501109
TI  - Endoscopic resection of chondrosarcomas of the nasal septum: a report of 2 cases.

PMID- 12501110
TI  - Tension orbital pneumocele secondary to nasal obstruction from cocaine abuse: a
      case report.

PMID- 12501111
TI  - Orbital paraffinoma as a complication of endoscopic sinus surgery.

PMID- 12501112
TI  - Cholesterol granuloma of the frontal bone.

PMID- 12501113
TI  - Chronic lymphocytic leukemia manifesting in the paranasal sinuses.

PMID- 12501114
TI  - Glomus jugulare.

PMID- 12501115
TI  - Guidelines for assessing and diagnosing acute psychosis: a primer.

PMID- 12501116
TI  - Nursing intervention and treatment of the acutely psychotic patient in the
      emergency department.

PMID- 12501117
TI  - Recent developments in pharmacotherapy for the acutely psychotic patient.

PMID- 12501118
TI  - Measuring antianginal drug efficacy using exercise testing for chronic angina:
      improved exercise performance with ranolazine, a pFOX inhibitor.

PMID- 12501119
TI  - Science and technology networks in Scandinavia.

PMID- 12501120
TI  - Building Nordic networks.

PMID- 12501121
TI  - Turning oil into science: Norway.

PMID- 12501122
TI  - Blurred vision.

PMID- 12501123
TI  - Bridging sectors. Medicon Valley.

PMID- 12501124
TI  - Biotechnology in the Medicon Valley.

PMID- 12501125
TI  - Finnish biotechnology--built on solid foundations.

PMID- 12501127
TI  - Safety and pharmacokinetic profile of multiple escalating doses of (+)-calanolide
      A, a naturally occurring nonnucleoside reverse transcriptase inhibitor, in
      healthy HIV-negative volunteers.
AB  - BACKGROUND: (+)-Calanolide A is a naturally occurring nonnucleoside reverse
      transciptase inhibitor (NNRTI) that exhibits enhanced activity against HIV-1
      isolates with the Y181C mutation and retains activity against HIV-1 isolates with
      dual Y181C and K103N mutations. Previous studies have demonstrated that (+)
      calanolide A has a favorable safety profile in both animal and human subjects.
      METHOD: In this study, the safety and pharmacokinetics of multiple escalating
      doses of (+)-calanolide A were evaluated in a total of 47 healthy, HIV
      seronegative individuals. RESULTS: All adverse events seen in the study were mild
      to moderate in intensity and were transient. The most common adverse events seen
      were headache, dizziness, nausea, and taste perversion (oily aftertaste).
      Laboratory abnormalities were determined to be clinically insignificant or
      unrelated to (+)-calanolide A administration. No dose-related pattern in adverse
      event or laboratory abnormality incidence was apparent. In all cohorts examined,
      administration of (+)-calanolide A produced highly variable plasma levels and
      absorption profiles. No accumulation of parent compound was seen over the 5-day
      treatment course, with the day 5 area under the curve (AUC) being approximately
      one half of that seen on the first day of dosing. Steady-state trough plasma
      levels were determined in the two highest dose cohorts (600 mg and 800 mg bid for
      5 days). Mean elimination half-life in the two highest dosing cohorts combined
      was 15.5 hours in men and 35.2 hours in women. CONCLUSION: These pharmacokinetic
      properties, together with the benign safety profile, and unique in vitro
      resistance pattern warrant the continued development of this potential new
      antiviral agent.

PMID- 12501128
TI  - Effect of highly active antiretroviral therapy (HAART) and hepatitis C Co
      infection on hyperlipidemia in HIV-infected patients: a retrospective
      longitudinal study.
AB  - BACKGROUND: Lipid abnormalities are among the most frequent treatment-limiting
      adverse events during HAART in HIV-infected individuals. Lipid disturbances have
      also been associated with hepatitis C virus (HCV) chronic infection in HIV
      uninfected participants. HAART-induced lipid abnormalities may then have peculiar
      features in HIV-HCV co-infected individuals. PURPOSE: To estimate the prevalence
      and incidence rates of hypertriglyceridemia and hypercholesterolemia and to
      identify associated factors in a large clinic population of HIV patients after
      HAART has been initiated. DESIGN: We performed a retrospective longitudinal
      follow-up study in a large cohort of HIV patients on their first HAART. PATIENTS
      AND METHOD: The clinical databases of two major clinical centers in Italy
      participating in the MASTER study were merged. Treatment-emerging metabolic
      disorders in patients on their first HAART regimen (PI-based or NNRTI-based) who
      were stable for at least 4 months were prospectively analyzed by baseline
      parameters, drug regimens, and viroimmunological outcome of therapy. Follow-up
      was continued for 24 months or until drug discontinuation, whichever came first.
      RESULTS: Two hundred and eighty two (282) HIV-infected patients undergoing HAART
      (203 PI + 79 NNRTI; 65 including stavudine [d4T]) met inclusion criteria and were
      enrolled in the study from 1997 to 2001. Mean follow-up was 18.5 +/- 6.7 months.
      After HAART had been initiated, a statistically significant mean increase in
      total cholesterol over time was observed in comparison to baseline (p <.0001),
      without difference between treatment groups (PI vs. NNRTI, with or without d4T).
      In the univariate analysis, predictive factors for HAART-induced
      hypercholesterolemia were baseline total plasma cholesterol and triglycerides
      values and CD4+ cell count differential increase over time, while a negative
      correlation was found with zalcitabine-including regimens and baseline HCV
      seropositivity. At multivariate analysis, only high baseline total plasma
      cholesterol and triglycerides values retained their predictive value and baseline
      HCV seropositivity was significantly associated with lower increase in total
      cholesterol values under HAART, regardless of treatment groups (p <.001).
      CONCLUSION: HCV co-infection is an independent factor preventing the emergence of
      treatment-limiting total cholesterol increase under any HAART regimen, possibly
      reflecting impaired total cholesterol synthesis in the liver or total cholesterol
      hypercatabolism. On the contrary, no HCV influence on triglycerides plasma levels
      was noted. Our data do not suggest any favoring role of specific treatment or
      drugs (PI and/or d4T) on total cholesterol and triglycerides increase under
      HAART.

PMID- 12501129
TI  - Does an increase in nevirapine plasma levels cause complete virologic suppression
      in patients experiencing early virologic failure?
AB  - BACKGROUND: Patients on two nucleoside analogs plus nevirapine (NVP) who show low
      level plasma HIV RNA might have insufficient NVP plasma levels and therefore
      might benefit from an increase in NVP dosing. METHOD: The dose of NVP was
      increased from 400 mg/day to 600 mg/day in 25 participants taking NVP-containing
      triple combinations for at least 3 months and experiencing a first virological
      failure (>50 HIV RNA copies/mL). The levels of NVP were measured in plasma
      samples taken prior to and 3 months after the intervention. HIV genotyping was
      performed at the time of dose increase. A control group of 25 participants who
      showed early virological failure with NVP continued with standard doses of the
      drug for 3 months. RESULTS: The median HIV RNA and CD4 cell counts were 100
      copies/mL and 635 cells/mm(3), respectively. Similar figures were recorded in the
      control arm. Mean NVP plasma levels that were reached with a dose of 600 mg/day
      were significantly higher than those with 400 mg/day (7.4 microg/mL [95% CI, 6.4
      8.4] vs. 3.4 microg/mL [95% CI, 2.9-3.9]; p <.0001). Thirteen (52%) participants
      reached <50 HIV RNA copies/mL after the intervention. The greater levels of NVP
      were relatively well tolerated, with no development of rashes and only mild
      elevations in transaminase levels. NVP-associated mutations were recognized in 9
      of 10 participants who did not respond but only in 3 of 9 responders (p =.019).
      More frequent mutations appeared at positions 181, 103, 106, and 190. The levels
      of NVP did not change significantly in participants who were included in the
      control arm, and only one reached complete virological suppression after
      continuing treatment for 3 additional months. CONCLUSION: An increase of one pill
      of NVP per day led to a significant rise in NVP plasma levels. A greater
      virologic response was noticed among participants with higher NVP plasma levels.
      Major resistance mutations that conferred resistance to NVP were recognized in
      all participants who failed to regain virological suppression after increasing
      NVP dose.

PMID- 12501130
TI  - HIV production from purified monocytes isolated from antiretroviral-naive and
      protease inhibitor-treated HIV-1-infected patients.
AB  - PURPOSE: We obtained peripheral blood monocytes from HIV-1-infected patients and
      differentiated them into macrophages in vitro to investigate the contribution of
      purified monocytes to plasma viremia in HIV-infected patients. METHOD: We
      compared the production of HIV-1 from purified monocytes isolated from patients
      who were receiving antiviral therapy to those who were not. We obtained monocytes
      from 29 antiretroviral-naive (ARVN) patients and 35 protease inhibitor (PI)
      treated HIV-infected patients (20 with undetectable plasma HIV). Cells were
      cultured with phorbol myristate acetate to induce HIV replication. RESULTS: HIV
      p24 core antigen was present in supernatants of 9/29 (31%) of ARVN patients (mean
      = 102 pg/mL). In contrast to ARVN patients, p24 was not found in supernatants of
      any PI-treated patient (p =.01). Thus, purified monocytes from some ARVN patients
      produce HIV, but we were unable to detect HIV production from monocytes from PI
      treated patients, regardless of their virologic response. CONCLUSION: Monocytes
      may contribute to plasma viremia in ARVN patients but may not do so in PI-treated
      patients.

PMID- 12501131
TI  - Placebo practice trials: a tool to assess and improve adherence readiness.
AB  - PURPOSE: Antiretroviral therapy is being increasingly delayed until later stages
      of illness. Therefore, prior to prescribing HAART, providers are emphasizing the
      need for patients to be ready to adhere well to the treatment regimen.
      Unfortunately, providers are no better than chance at predicting a patient's
      adherence, and there are no established methods for accurately assessing a
      patient's adherence readiness. This pilot study assessed the utility of a series
      of up to five 1-week placebo practice trials accompanied by adherence counseling
      as a clinical tool to both assess and improve adherence readiness. METHOD:
      Participants were not prescribed treatment until they demonstrated readiness,
      which was defined as 90+% adherence during a single practice trial. Once HAART
      was initiated, adherence to one selected antiretroviral was monitored for 4
      weeks. Electronic monitoring caps were used to measure adherence. RESULTS: Twenty
      men enrolled in the study at two HIV outpatient clinics in Southern California.
      Mean age was 33, 50% were non-White, 35% were employed, 30% had not completed
      high school, 15% were Spanish monolingual, and 30% had unstable housing. Nine
      participants achieved 90+% adherence in the first practice trial, with an
      additional 8 participants demonstrating readiness after two to four practice
      trials; two participants withdrew from the study because of intolerance of the
      restrictions related to the use of the caps; and one participant was removed from
      the study after no effort was given during two practice trials. Of the 17
      participants who completed the program and demonstrated adherence readiness, 15
      started on an antiretroviral regimen and 2 decided to defer treatment
      indefinitely. Of the 15 who started therapy, 13 (87%) achieved 90+% adherence
      during the first month of antiretroviral therapy. The sample's mean adherence
      during the first 4 weeks of treatment was 93% (SD = 13). CONCLUSION: These
      results suggest that once a patient is able to adhere well to a 1-week practice
      trial they are likely to adhere equally well to HAART. A larger controlled study
      is needed to further assess the effectiveness of practice trials as a clinical
      tool for both assessing and improving adherence readiness.

PMID- 12501132
TI  - Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV
      infected participants.
AB  - PURPOSE: To evaluate the impact of selenium chemoprevention (200 microg/day) on
      hospitalizations in HIV-positive individuals. METHOD: Data were obtained from 186
      HIV+ men and women participating in a randomized, double-blind, placebo
      controlled selenium clinical trial (1998-2000). Supplements were dispensed
      monthly, and clinical evaluations were conducted every 6 months. Inpatient
      hospitalizations, hospitalization costs, and rates of hospitalization were
      determined 2 years before and during the trial. RESULTS: At enrollment, no
      significant differences in CD4 cell counts or viral burden were observed between
      the two study arms. Fewer placebo-treated participants were using antiretrovirals
      (p <.05). The total number of hospitalizations declined from 157 before the trial
      to 103 during the 2 year study. A marked decrease in total admission rates (RR =
      0.38; p =.002) and percent of hospitalizations due to infection/100 patients for
      those receiving selenium was observed (p =.01). As a result, the cost for
      hospitalization decreased 58% in the selenium group, compared to a 30% decrease
      in the placebo group (p =.001). In the final analyses, selenium therapy continued
      to be a significant independent factor associated with lower risk of
      hospitalization (p =.001). CONCLUSION: Selenium supplementation appears to be a
      beneficial adjuvant treatment to decrease hospitalizations as well as the cost of
      caring for HIV-1-infected patients.

PMID- 12501134
TI  - Selected topics from the XI International HIV Drug Resistance Workshop, Seville,
      and the XIV International AIDS Conference, Barcelona.

PMID- 12501133
TI  - Intracellular concentration of protease inhibitors in HIV-1-infected patients:
      correlation with MDR-1 gene expression and low dose of ritonavir.
AB  - BACKGROUND: Protease inhibitors (PIs) are substrates for the P-glycoprotein (P
      gp/170) encoded by the multi-drug resistance gene (MDR-1). HIV infection is
      associated with increased expression of P-gp. The role of MDR gene overexpression
      in clinical pharmacokinetics is not known. METHOD: We determined by HPLC, at
      trough and peak levels, the current PI concentrations in plasma (P) and in
      peripheral blood mononuclear cells (PBMCs) (intracellular concentration [IC])
      from 49 HIV-infected patients receiving different treatment combinations:
      nelfinavir ([NFV] n = 12); indinavir ([IDV] n = 10); amprenavir ([APV] n = 5);
      ritonavir (RTV) 100 bid/IDV 800 mg bid (n = 6); RTV 400 bid/IDV 400 mg bid (n =
      3); RTV 100 bid/saquinavir (SQV) 600 mg tid (n = 9); APV 600 bid/RTV 100 mg bid
      (n = 4). We determined the mean ratio of intracellular/plasma PI concentration
      for each treatment group. The MDR-1 gene expression was determined by a semi
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR). HIV viral
      load was simultaneously measured. RESULTS: 49 patients (mean age 41 +/- 8.7
      years; mean CD4 cell count 418 [57-972]; mean HIV RNA 2.1 +/- 0.8 log(10)) were
      included in the study. Patients who overexpressed the MDR-1 gene had
      significantly lower trough intracellular PI levels (p =.02) or lower
      intracellular accumulation of PI (p =.042). Patients treated with low-dose RTV in
      combined regimens with detectable RTV intracellular concentration showed lack of
      MDR-1 gene expression (p =.01). Patients with HIV RNA < 40 copies/mL had
      significantly higher RTV intracellular accumulation (p =.029). CONCLUSION: In HIV
      infected patients, IC of PI is inversely correlated with MDR-1 gene
      overexpression. Undetectable viral load was associated with the use of low-dose
      RTV, probably linked to better intracellular accumulation of the drug.
      Nevertheless, further investigation is needed to confirm these results.

PMID- 12501136
TI  - The effect of disinfectants on the properties of dental gypsum, part 2: surface
      properties.
AB  - PURPOSE: This study is part of an ongoing investigation to evaluate the surface
      properties of dental stones mixed with disinfection solutions, and to determine
      the effect of adding gum arabic and calcium hydroxide on the same properties.
      MATERIALS AND METHODS: Aqueous solutions of 2 chemical disinfectants were used in
      mixing 2 types of dental stones (type III and type V). These dental stones were
      modified further by adding 1% gum arabic and 0.132% calcium hydroxide to their
      hemihydrate powders before mixing. Five specimens prepared from each type of
      dental stone were classified into 7 groups according to the hemihydrate powder
      modification and mixing liquid/powder ratio. Surface roughness was tested by 2
      dimensional profilometery and scanning electron microscopy (SEM). Knoop hardness
      testing was carried out, and detail reproduction was assessed using ADA
      specification 25 in addition to SEM and 3-dimensional profilometer studies.
      RESULTS: Dental stones mixed with chemical disinfectants showed higher average
      roughness (R(a)) values than those of the controls. However, adding gum arabic
      and calcium hydroxide to the hemihydrate powders before mixing restored values to
      the level of the control. The additives seemed to have a role in the improvement
      of surface hardness. There was no significant difference between the experimental
      and the control group in the terms of detail reproduction. CONCLUSIONS: Using
      SEM, 3-dimensional profilometry, and ADA testing methods, we found that the
      surface roughness of stone casts was adversely affected by using the disinfectant
      solutions as mixing water substitutes. Gum arabic and calcium hydroxide additives
      can yield a harder stone surface without compromising other surface properties.

PMID- 12501137
TI  - Modulated bone matrix-related gene expression is associated with differences in
      interfacial strength of different implant surface roughness.
AB  - PURPOSE: The objective of this study was to examine the effect of implant surface
      topography on biomechanical strength and expression patterns of bone
      extracellular matrix (ECM)-related genes during implant healing. MATERIALS AND
      METHODS: Cylinder implants with turned or dual acid-etched (DE) surface were
      placed into the femurs of female Sprague-Dawley rats. At 2 and 4 weeks after the
      implantation, the implant push-in test was performed to measure the load-bearing
      strength of the bone-tissue interface. T-shaped hollow implants were separately
      placed and the total RNA was extracted from the ingrown tissue within the hollow
      chamber. The RNA was subjected to reverse transcriptase polymerase chain reaction
      to analyze the expression pattern of selected bone extracellular matrix-related
      genes. RESULTS: The push-in value of the DE implant is approximately 300% greater
      than that of the turned implant at weeks 2 and 4 (p=.0090). The expression of
      collagen II, osteocalcin and biglycan was higher in the week 2 DE implant group
      than the turned implant group. At week 4 the expression of collagen II and IX was
      7- and 26-fold, respectively, greater in the DE implant group than in the turned
      implant group. CONCLUSIONS: The surface topography of implants may induce the
      phenotypic alteration of wound healing cells. The increased interfacial strength
      of the DE implant may be associated with the modulated expression of the selected
      set of bone extracellular matrix genes.

PMID- 12501138
TI  - In vitro examination of the fracture strength of 3 different fiber-reinforced
      composite and 1 all-ceramic posterior inlay fixed partial denture systems.
AB  - PURPOSE: This in vitro study was carried out to examine the fracture strength of
      metal- free posterior inlay fixed partial dentures (IFPDs). The 3-unit IFPDs were
      made of either a polyethylene fiber-reinforced composite, 3 glass fiber
      reinforced composites, or an all-ceramic material. MATERIALS AND METHODS: Eight
      IFPDs were fabricated of each material in accordance with the manufacturer's
      instructions and luted to extracted human molars with a dual-cure adhesive
      system. The molars were positioned in PMMA resin 10 mm apart mesiodistally. Inlay
      cavity preparations with enamel finishing lines were used. After thermal cycling
      and mechanical loading in an artificial oral environment, the cemented IFPDs were
      mechanically loaded until failure. Visual and radiologic examinations were done
      out to discern the different forms of fracture. Median and 25%/75% percentile
      values were calculated. Statistical analysis was performed using the Mann-Whitney
      U test and the Kruskal-Wallis test (p< or =0.05). RESULTS: With a median (and
      25%/75% percentile) fracture strength of 368 N (234 N/424 N), the
      FibreKor/Conquest Sculpture showed significantly lower values than the
      Connect/BelleGlass [898 N (736 N/1033 N)], Vectris/Targis [723 N (692 N/806 N)],
      Everstick/Sinfony [634 N (532 N/673 N)], and Empress2 [520 N (385 N/706 N)].
      CONCLUSIONS: Assuming maximum chewing forces of > or =500N in posterior areas,
      all systems showed sufficient fracture strength in most cases and warrant further
      investigation for potential clinical use.

PMID- 12501139
TI  - The influence of plasticizer loss on the viscoelasticity of temporary soft
      liners.
AB  - PURPOSE: This study examined the changes in mechanical properties of temporary
      soft liners introduced by the differential loss of alcohol and plasticizer in
      different storage media. MATERIALS AND METHODS: Four brands of temporary soft
      liners were used to prepare 128 specimens on Lucite LS substrates. Each group of
      specimens was stored in a different medium (air, 10% ethanol, water, and
      artificial saliva), selected to affect the levels of plasticizer and alcohol over
      time. Data on weight changes, plasticizer leaching, and recovery rate were
      recorded at the following intervals: baseline, 2, 7, 14, 28, 56, and 176 days.
      The storage media were periodically renewed except during the drying stage
      between day 56 and 176. Two-way analysis of variance and Duncan multiple-range
      tests were performed. RESULTS: Plasticizer leaching occurs at higher levels in
      artificial saliva than in other storage media (P <.0001). The mean recovery rates
      exhibited a statistically significant increase (indicating reduced
      viscoelasticity) in more of the artificial saliva specimens than in all other
      test groups (P <.0001). Comparatively, the rates of recovery were lower in the
      10% ethanol storage medium (except Lynal) with a statistically significant
      difference attained with the higher air-stored specimens in Tempo and Coe-Comfort
      (P <.0001). During the drying phase, weight changes in the 10% ethanol group were
      higher than those in the other storage media. CONCLUSIONS: The study supports the
      contention that alcohol may have been retained in the 10% ethanol group in a
      manner that extended the viscoelasticity of the material. The roles of alcohol
      and plasticizer content in the mechanical properties of temporary soft liners
      depend on the type of temporary soft liners and on the nature/duration of service
      desired. Storing dentures lined with tissue conditioners under dry conditions and
      those lined with true soft-liners in an ethanol humidor may be justified to
      extend serviceability by minimizing the loss of the component most relevant to
      viscoelasticity.

PMID- 12501140
TI  - In vitro wear assessment of titanium alloy teeth.
AB  - PURPOSE: Wear of commercially pure (CP) titanium prosthetic teeth has frequently
      been observed. The greatest wear has been found when the same grades of CP
      titanium are used for both maxillary and mandibular teeth. This study examined
      the wear behavior of teeth made with cast titanium alloy and compared these
      results with those for CP titanium and gold alloy teeth. MATERIALS AND METHODS:
      All tooth specimens were cast with grade 3 alpha titanium, 3 metastable beta
      alloys [Ti-15Mo-2.8Nb-0.2Si (Timetal 21 SRx), Ti-13Nb-13Zr, and Ti-15V-3Cr-3Sn
      3Al], and 2 alpha+beta alloys (Ti-6Al-7Nb and Ti-6Al-4V). As a control, Type IV
      gold alloy was also cast conventionally. All teeth (both maxillary and
      mandibular) were secured in an in vitro 2-body wear testing apparatus that
      simulated chewing function (60 strokes/min; grinding distance, 2 mm under flowing
      water). Wear resistance was assessed as volume loss (mm(3)) at 5 kgf (grinding
      force) after 50,000 strokes. The results (n = 5) were analyzed using analysis of
      variance or Fisher's exact test (alpha = 0.05). RESULTS: Of the titanium teeth,
      the wear of 2 of the metastable beta alloys (Timetal 21 SRx and Ti-15V-3Cr-3Sn
      3Al) was found to be significantly (p <0.05) higher than that of CP titanium and
      the 2 alpha+beta alloys. The Type IV gold alloy exhibited better wear resistance
      than all of the titanium teeth tested. No correlation was found between wear loss
      and hardness among all the metals tested. CONCLUSIONS: Among the titanium teeth
      examined, the alpha+beta alloys exhibited significantly less wear than the other
      types of titanium. The dental casting gold alloy tested exhibited the best wear
      resistance among all of the metals tested.

PMID- 12501141
TI  - An evaluation of the viscoelastic characteristics of soft denture liners.
AB  - PURPOSE: The purpose of this study was to evaluate the viscoelastic
      characteristics of a group of soft denture liners by means of a creep test.
      MATERIALS AND METHODS: The materials evaluated included a silicone rubber base
      direct liner (Sofreliner MS), a polyolefin base indirect liner (Molteno S), and a
      conventional tissue conditioner (Coe Soft) as a control. Cylindrical specimens of
      each material were fabricated using a metal mold. Half of the specimens were
      subjected to mechanical fatigue with a 75-N load at 1.2 Hz for 200,000 cycles.
      The creep test was performed on each material and condition with and without a
      fatigue test using low-load conditions to achieve a 10% strain on all specimens.
      Viscosity and elasticity were measured, and the data were statistically analyzed
      using 1-way analysis of variance and Fisher's Protected Least Significant
      Difference (PLSD) test (p < 0.05). RESULTS: The silicone rubber direct liner
      (1.31 +/- 2.1 MPa) exhibited a similar mean elastic property as the conventional
      tissue conditioner (0.90 +/- 0.22 MPa) and an intermediate viscosity between the
      conventional tissue conditioner (0.11 +/- 0.01 GPa. s) and polyolefin base
      indirect liner (9.84 +/- 1.08 GPa. s). The elasticity did not change for
      polyolefin and silicone rubber after the fatigue process. Significant differences
      in the viscosity of silicone rubber were seen with and without fatigue testing (p
      < or = 0.05). CONCLUSIONS: The silicone rubber was as soft as the tissue
      conditioner and softer than the polyolefin liner. The stiffer the material, the
      lower the permanent deformation observed.

PMID- 12501143
TI  - Photographing objects: backgrounds and techniques.

PMID- 12501144
TI  - The history of articulators: a critical history of articulators based on
      geometric theories of mandibular movement, part III: the "balancer" designs.

PMID- 12501147
TI  - Predictors of intensive care unit and hospital length of stay in diabetic
      ketoacidosis.
AB  - OBJECTIVE: To determine the predictive value for prolonged intensive care unit
      (ICU) and hospital length of stay (LOS) in patients with diabetic ketoacidosis
      (DKA) of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score
      and Logistic Organ Dysfunction System (LODS), and to identify associated
      characteristics. DESIGN: Prospective cohort, 18-month observation. SUBJECTS AND
      SETTING: All admissions to a 12-bed, inner-city, university-affiliated hospital,
      medical ICU from July 1999 to December 2000. MEASUREMENTS: Data for APACHE II and
      LODS scoring systems were collected within 24 hours of admission. Lengths of ICU
      and hospital stay were the primary outcomes. Prolonged ICU and hospital LOS were
      defined as 3 or more and 6 or more days. RESULTS: A total of 584 patients, mean
      age 49, 56% men, 82% African American were admitted to the ICU. At admission they
      had (mean +/-SD) APACHE II (18 +/- 10), LODS (5 +/- 4), and predicted mortality
      of 32% +/- 29%. DKA was the admitting diagnosis in 42 (7.6%) patients; they had
      lower APACHE II (12 +/- 6), LODS (2 +/- 1), and predicted mortality 5% +/- 5%
      than the general ICU population (all, P <.001). Hospital mortality in non-DKA
      patients was 18%; there were no deaths in patients with DKA. Among DKA patients,
      those with insulin noncompliance had a shorter hospital stay (2.8 +/- 1 d) than
      those with an underlying illness as the DKA trigger (4.8 +/- 3, P =.02). Between
      patients with DKA, regardless of the LOS, there were no significant differences
      in APACHE II, LODS, or predicted mortality. CONCLUSIONS: ICU-admitted patients
      with DKA are less ill, and have lower disease severity scores, mortality, and
      shorter length of ICU and hospital stay than non-DKA patients. Disease severity
      scores are not, but precipitating cause is, predictor associated with prolonged
      hospital LOS in patients with DKA.

PMID- 12501148
TI  - Alcohol problems among young adult emergency department patients: making
      predictions using routine sociodemographic information.
AB  - OBJECTIVES: The study aims were to explore the process of identifying young adult
      Emergency Department (ED) patients at risk for alcohol problems, examine the
      sociodemographic predictors of patient alcohol problems, and determine
      differences between patients who screened positive and those who screened
      negative for alcohol problems. Implications for ED practice are discussed.
      METHOD: As part of a larger study, the Alcohol Use Disorders Identification Test
      was administered to consenting patients ages 18 to 29. A score of greater than 5
      (out of 40) was considered a positive screen for alcohol problems.
      Sociodemographic information was collected from a generic Individual Information
      Form. RESULTS: Approximately 48% (1855 of 3890) of patients screened positive for
      alcohol problems. Among screen-positive patients, 91% (1689) had scores that
      corresponded to mild to moderate alcohol problems. Compared with screen-negative
      patients, screen-positive patients were almost 3 times more likely to be men
      (odds ratio [OR] = 2.70); 2.5 times more likely to use tobacco (OR = 2.43); 2
      times more likely to be single (OR = 2.03); and 1.5 times more likely to have
      some college education (OR = 1.41), be an 18- to 20-year-old adult (OR = 1.61),
      be a college student (OR = 1.60), be unemployed (OR = 1.39), and cohabitate with
      friends (OR = 1.19). Screen-positive patients also were more likely to have made
      at least one past attempt to change their drinking behavior (OR = 3.21).
      CONCLUSION: Routine patient information presented an accurate risk profile for
      alcohol problems among patients in this study. If ED-based health care
      professionals routinely screened patients for alcohol problems or could predict
      potential alcohol problems by using routinely collected information, then
      intervention or referral for additional services may increase.

PMID- 12501149
TI  - Health services research rounds: patient-centered outcomes.

PMID- 12501150
TI  - Predictors for mortality after prolonged mechanical ventilation after cardiac
      surgery in children.
AB  - PURPOSE: To identify early mortality-associated clinical risk factors preceding,
      during, and after cardiac surgery in children. MATERIALS AND METHODS: Of the 722
      children admitted to our pediatric intensive care unit (PICU) from January 1992
      to January 1997 after repair of congenital heart defects, 70 required 48 hours or
      more of mechanical ventilation. Their clinical records were analyzed for
      perioperative predictors of mortality. RESULTS: The children's ages were 3.6 +/-
      4.1 years (range, 4 d-16 y). The overall mortality was 5.9%. Eleven of the 70
      children (15.7%) who required mechanical ventilation for 48 hours or more did not
      survive compared with 30 of the 652 (4.6%) children ventilated for less than 48
      hours. The preoperative predictors identified as being significantly associated
      with increased mortality were younger age (P <.05) and the presence of congestive
      heart failure (P <.01). The main cause of early postoperative mortality was
      multiorgan dysfunction (9 children, 81.8%), whereas septic complications also
      were responsible for late (< 1 wk postoperatively) death (the other 2 children,
      17.2%). CONCLUSIONS: Younger age and congestive heart failure were the main
      preoperative predictors of mortality. Multiorgan dysfunction and septic
      complication were predictive of an increased risk for death after cardiac
      surgery. These factors should be investigated in greater depth to assist in
      guiding aggressive therapeutic approaches for combating early signs of organ
      system dysfunction and infectious complications in these high-risk patients.

PMID- 12501151
TI  - Occurrence of ventilator-associated pneumonia in mechanically ventilated
      pediatric intensive care patients during stress ulcer prophylaxis with
      sucralfate, ranitidine, and omeprazole.
AB  - PURPOSE: The purpose of the study was to evaluate the effects of sucralfate,
      ranitidine, and omeprazole use on incidence of ventilatory-associated pneumonia
      (VAP) and mortality in ventilated pediatric critical care patients. MATERIALS AND
      METHODS: This prospective study was conducted at the pediatric intensive care
      unit (PICU) between August 2000 and February 2002. A total of 160 patients who
      needed mechanical ventilation were randomized into 4 groups according to the
      computer-generated random number table: group (S), (n = 38) received sucralfate
      suspension 60 mg/kg/d in 4 doses via the nasogastric tube that was flushed with
      10 mL of sterile water; group (R), (n = 42) received ranitidine 2 mg/kg/d
      intravenously in 4 doses; group (O), (n = 38) received omeprazole 1 mg/kg/d
      intravenously in 2 doses; and group (P), (n = 42) did not receive any medication
      for stress ulcer prophylaxis. Treatment was begun within 6 hours of PICU
      admission. RESULTS: Seventy patients (44%) developed VAP. VAP rate was 42% (16 of
      38) in the sucralfate group, 48% (20 of 42) in the ranitidine group, 45% (17 of
      38) in the omeprazole group, and 41% (17 of 42) in the nontreated group. Overall
      mortality rate was 22% (35 of 160); it was 21% (8 of 38) in the sucralfate group,
      23% (10 of 42) in the ranitidine group, 21% (8 of 38) in the omeprazole group,
      and 21% (9 of 42) in the nontreated group. Our results did not show any
      difference in the incidence of VAP and mortality in mechanically ventilated PICU
      patients treated with ranitidine, omeprazole, or sucralfate, or nontreated
      subjects (P =.963, confidence interval [CI] = 0.958-0.968; P =.988, CI = 0.985
      0.991, respectively). Nine patients (5.6%) had macroscopic bleeding. There was no
      statistically significant difference in macroscopic bleeding between groups.
      CONCLUSIONS: Our results did not show any difference in the incidence of VAP,
      macroscopic stress ulcer bleeding, and mortality in the mechanically ventilated
      PICU patients treated with ranitidine, omeprazole, or sucralfate, or nontreated
      subjects. None of the treatment regimens increased VAP compared with the
      nontreated group. Because there is insufficient data about stress ulcer
      prophylaxis and VAP in the pediatric age group, more studies with larger numbers
      of patients are needed.

PMID- 12501152
TI  - Dosing patterns for continuous renal replacement therapy at a large academic
      medical center in the United States.
AB  - PURPOSE: We sought to retrospectively review the dosing patterns of continuous
      renal replacement therapy (CRRT) in patients with acute renal failure (ARF) and
      determine their actual delivered dosage of CRRT. MATERIALS AND METHODS:
      Computerized records of patients (n = 115) who received CRRT for ARF at a single,
      large, academic, tertiary care hospital from September 1, 1999 through August 31,
      2000 were reviewed. The delivered dose of CRRT for each patient/day was
      calculated from the hourly effluent flow rate, the patient's weight, and the
      duration (in hours) of CRRT for that day. A mean effluent flow rate (in L/h) for
      each patient was then calculated. RESULTS: The average number of hours/day on
      CRRT was 16.1 +/- 3.53 (mean +/- SD), with a mean flow rate (averaged over 24 h)
      of 1.36 +/- 0.31 L/h. The mean CRRT dose prescribed for these patients was 24.46
      +/- 6.73 mL/Kg/h, but the mean dose delivered was only 16.55 +/- 5.41 mL/Kg/h
      (68% of the prescribed dose, P <.000001). CONCLUSIONS: Many patients are
      prescribed low doses of CRRT. Furthermore, the dose delivered is considerably
      lower than that prescribed. Methods and procedures to extend CRRT system life may
      improve the dose delivery.

PMID- 12501153
TI  - Purulent pneumococcal pericarditis: a rarity in the antibiotic era.
AB  - PURPOSE: The purpose of this report is to show that even while properly treated,
      pneumococcal disease may proceed to a life-threatening condition including
      purulent pericarditis and multiple organ failure. PATIENTS AND METHODS: This is a
      case-report describing one patient treated in the intensive care unit (ICU) of
      Helsinki University Central Hospital in March 2001. CONCLUSIONS: In the
      antibiotic era, purulent pericarditis is an extremely rare yet possible condition
      complicating pneumococcal disease. Because of the growing incidence of penicillin
      resistance of this community-acquired pathogen, purulent pericarditis may become
      more common. Early detection and treatment of this otherwise fatal condition may
      lead to a good outcome.

PMID- 12501154
TI  - Magnesium sulfate administered via continuous intravenous infusion in pediatric
      patients with refractory wheezing.
AB  - PURPOSE: To evaluate the dosing and safety of intravenous magnesium sulfate
      administered via continuous infusion for refractory wheezing. MATERIALS AND
      METHODS: All patients admitted to the pediatric intensive care unit (PICU)
      between January 1998 and March 2001 who were prescribed magnesium sulfate via
      continuous infusion were identified via retrospective chart review. The patient's
      medical history, demographic data, vital signs, magnesium dosing history, and
      concurrent medications were recorded. RESULTS: Forty PICU patients represent our
      study population. The mean age was 82.6 +/- 64.6 mo; 18 patients were boys.The
      mean magnesium loading dose (mg/kg) was 29.6 +/- 13.2 with a mean infusion dose
      (mg/kg/h) of 18.4 +/- 6.5 with a significant difference in dosing noted between
      patients weighing less than 30 kg and those with a higher weight. The mean
      magnesium loading dose (mg/kg) in the less than 30 kg group was 35.3 +/- 12.7
      compared with 21.9 +/- 9.9 in the higher weight group (P <.05). Mean infusion
      doses (mg/kg/h) were 21.6 +/- 6 and 14.6 +/- 4.2, respectively (P <.05). There
      was no significant difference between the mean concentrations (mg/dL) reported
      between the 2 groups (less than 30 kg group = 3.9 +/- 0.6; higher weight group =
      3.6 +/- 0.5). All patients received nebulized albuterol, ipratropium, and
      intravenous methylprednisolone before magnesium therapy. Aminophylline and
      ketamine were prescribed to 28 and 4 patients, respectively. No cardiovascular
      adverse effects were noted during magnesium therapy. CONCLUSIONS: For the
      treatment of refractory wheezing, intravenous magnesium sulfate administered via
      continuous infusion represents a safe mode of drug delivery.

PMID- 12501155
TI  - Noninvasive monitoring of cardiac output in human neonates and juvenile piglets
      by inductance cardiography (thoracocardiography).
AB  - PURPOSE: Thoracocardiography has been used in adult patients to noninvasively
      estimate changes in cardiac output (CO) by analysis of ventricular volume curves
      recorded by an inductive plethysmographic transducer encircling the chest at the
      level of the heart. The purpose of this study was to investigate the potential of
      thoracocardiography to monitor cardiac output in human neonates and in a small
      animal model, the juvenile piglet. MATERIALS AND METHODS: In 6 human premature
      neonates weighing 1.0 to 1.6 kg the effect of periodic respiration on CO was
      studied with thoracocardiography. In 9 piglets weighing 8.5 to 10.2 kg changes in
      CO were estimated simultaneously by thoracocardiography and thermodilution during
      fluid loading and rapid atrial pacing. RESULTS: In human neonates, CO during
      breathing was 136% to 320% of the corresponding value during apneas. In piglets,
      CO by thermodilution ranged from 0.25 to 3.26 L/min. The mean difference in 40
      paired estimates of relative changes in CO by thoracocardiography and
      thermodilution was 3%, limits of agreement (bias +/- 2 SD) were +/- 30%.
      CONCLUSIONS: In neonates, increases in CO during respiratory phases of periodic
      breathing are consistent with expected cardiorespiratory interactions.
      Thoracocardiography monitored changes in CO in piglets with acceptable accuracy.
      Thoracocardiography holds promise for noninvasive monitoring in human neonates
      but further validation is required.

PMID- 12501156
TI  - A paradigm shift is needed in proteomics: 'structure determines function' should
      be replaced by 'binding determines function'.

PMID- 12501157
TI  - Survey of the year 2001 commercial optical biosensor literature.
AB  - We have assembled references of 700 articles published in 2001 that describe work
      performed using commercially available optical biosensors. To illustrate the
      technology's diversity, the citation list is divided into reviews, methods and
      specific applications, as well as instrument type. We noted marked improvements
      in the utilization of biosensors and the presentation of kinetic data over
      previous years. These advances reflect a maturing of the technology, which has
      become a standard method for characterizing biomolecular interactions.

PMID- 12501158
TI  - The Poisson-Boltzmann equation for biomolecular electrostatics: a tool for
      structural biology.
AB  - Electrostatics plays a fundamental role in virtually all processes involving
      biomolecules in solution. The Poisson-Boltzmann equation constitutes one of the
      most fundamental approaches to treat electrostatic effects in solution. The
      theoretical basis of the Poisson-Boltzmann equation is reviewed and a wide range
      of applications is presented, including the computation of the electrostatic
      potential at the solvent-accessible molecular surface, the computation of
      encounter rates between molecules in solution, the computation of the free energy
      of association and its salt dependence, the study of pKa shifts and the
      combination with classical molecular mechanics and dynamics. Theoretical results
      may be used for rationalizing or predicting experimental results, or for
      suggesting working hypotheses. An ever-increasing body of successful applications
      proves that the Poisson-Boltzmann equation is a useful tool for structural
      biology and complementary to other established experimental and theoretical
      methodologies.

PMID- 12501159
TI  - Essential motions in a fungal lipase with bound substrate, covalently attached
      inhibitor and product.
AB  - As an aid to understanding the influence of dynamic fluctuations during
      esterolytic catalysis, we follow protein flexibility at three different steps
      along the catalytic pathway from substrate binding to product clearance via a
      covalently attached inhibitor, which represents a transition-state mimic. We have
      applied a classical approach, using molecular dynamics simulations to monitor
      protein dynamics in the nanosecond regime. We filter out small amplitude
      fluctuations and focus on the anharmonic contributions to the overall dynamics.
      This 'essential dynamics' analysis reveals different modes of response along the
      pathway suggesting that binding, catalysis and product clearance occur along
      different energy surfaces. Motions in the enzyme with a covalently attached
      ligand are more complex and occur along several eigenvectors. The magnitudes of
      the fluctuations in these individual subspaces are significantly smaller than
      those observed for the substrate and product molecules, indicating that the
      energy surface is shallow and that a relatively large number of conformational
      substates are accessible. On the other hand, substrate binding and product
      release occur at distinct modes of the protein flexibility suggesting that these
      processes occur along rough energy surfaces with only a few minima. Detailed
      energetic analyses along the trajectories indicated that in all cases binding is
      dominated by van der Waals interactions. The carboxylate form of the product is
      stabilized by a tight hydrogen bond network involving in particular Ser82, which
      may be a potential cause of product inhibition. Considerations such as these
      should aid the understanding of mechanisms of substrate, inhibitor or product
      recognition and could become of importance in the design of new substrates or
      inhibitors for enzymes.

PMID- 12501160
TI  - Protein-protein interactions: mechanisms and modification by drugs.
AB  - Protein-protein interactions form the proteinaceous network, which plays a
      central role in numerous processes in the cell. This review highlights the main
      structures, properties of contact surfaces, and forces involved in protein
      protein interactions. The properties of protein contact surfaces depend on their
      functions. The characteristics of contact surfaces of short-lived protein
      complexes share some similarities with the active sites of enzymes. The contact
      surfaces of permanent complexes resemble domain contacts or the protein core. It
      is reasonable to consider protein-protein complex formation as a continuation of
      protein folding. The contact surfaces of the protein complexes have unique
      structure and properties, so they represent prospective targets for a new
      generation of drugs. During the last decade, numerous investigations have been
      undertaken to find or design small molecules that block protein dimerization or
      protein(peptide)-receptor interaction, or on the other hand, induce protein
      dimerization.

PMID- 12501161
TI  - Brownian dynamics of interactions between aldolase mutants and F-actin.
AB  - Previous Brownian dynamics (BD) simulations (Ouporov IG, Knull HR and Thomasson
      KA 1999. Biophys. J. 76: 17-27) of complex formation between rabbit aldolase and
      F-actin have identified three lysine residues (K288, K293 and K341) on aldolase
      and acidic residues (DEDE) at the N-terminus of actin as important to binding. BD
      simulations of computer models of aldolase mutants with any of these lysine
      residues replaced by alanine show reduced binding energy; the greatest effect of
      a single substitution is for K341A, and replacement of all three lysines greatly
      reduces binding. BD simulations of wild-type rabbit aldolase vs altered F-actin
      show that binding is decreased if any one of the four N-terminal acidic residues
      is replaced by alanine and binding is greatly reduced if three or more of the N
      terminal acidic residues are replaced; none of the four actin residues appear
      more critical for binding than the others.

PMID- 12501162
TI  - Impact of the surgeon on cancer management outcomes.

PMID- 12501163
TI  - Anal sphincter preservation in locally advanced low rectal adenocarcinoma after
      preoperative chemoradiation therapy and coloanal anastomosis.
AB  - BACKGROUND AND OBJECTIVES: Standard treatment of rectal adenocarcinoma located 3
      6 cm above anal verge is abdominoperineal resection. The objective was to
      evaluate feasibility, morbidity, and functional results of anal sphincter
      preservation after preoperative chemoradiation therapy and coloanal anastomosis
      in patients with rectal adenocarcinoma located between 3 and 6 cm above the anal
      verge. METHODS: This study included 17 males and 15 females with a mean age of
      54.8 +/- 15.4 years. Tumors were located at a mean of 4.7 +/- 1.1 cm above the
      anal verge. The mean tumor size was 4.6 +/- 1.5 cm. All patients received the
      scheduled treatment. Twenty-two patients underwent coloanal anastomosis with the
      J pouch; 10 underwent straight anastomosis. Average surgical time was 328.7 +/-
      43.8 min, and the average intraoperative hemorrhage was 471.5 +/- 363.6 ml. The
      mean distal surgical margin was 1.3 +/- 0.6 cm. Five patients (15.6%) received a
      blood transfusion. RESULTS: Major complications included coloanal anastomotic
      leakage (three); pelvic abscess (three), and coloanal stenosis (two). Tumor
      stages were as follows: T0-2,N0,M0 = 12; T3,N0,M0 = 9; T1-3,N+,M0 = 9, and T1
      3,N0-3,M+ = 2. Diverting stomas were closed in 30 patients. Median follow-up was
      25 months. Recurrences occurred in four patients and were local and distant (n =
      1) and distant (n = 3). Anal sphincter function was perfect (n = 20), incontinent
      to gas (n = 3), occasional minor leak (n = 2), frequent major soiling (n = 3),
      and colostomy (n = 2). CONCLUSIONS: In patients with locally advanced rectal
      cancer located 3-6 cm from anal verge who are traditionally treated with
      abdominoperineal resection, preservation of anal sphincter after preoperative
      chemoradiation therapy plus complete rectal excision with coloanal anastomosis is
      feasible and is associated with acceptable morbidity and no mortality.

PMID- 12501164
TI  - Role of metastasectomy in the management of thyroid carcinoma: the NIH
      experience.
AB  - BACKGROUND AND OBJECTIVES: We studied the impact of metatasectomy on disease
      outcome in 29 advanced nonmedullary thyroid carcinoma (ThyrCa) patients who were
      operated on between 1969 and 2001 at NIH to further define its role in the
      management of this malignancy. METHODS: Data were extracted by retrospective
      chart review. A Kaplan-Meyer survival curve was constructed, and comparative
      stratification for various parameters was performed. RESULTS: During 47
      surgeries, the following lesions were resected from mid-mediastinum/hila, 17;
      lung parenchyma, 12; skeleton, 14; kidneys, 2; and brain, 2. All patients
      received multiple radioiodine (RAI) treatments. External-beam radiotherapy,
      chemotherapy and other palliative measures were used in selected patients. Six
      patients (21%) died within 74.7 +/- 54.7 months after the first distant
      metastasectomy. The outcome of the remaining patients was as follows: complete
      remission, 3; partial remission, 10; and 10: progressive disease, 10, with a
      follow-up of 175 patient-years. Metastasectomy led to a decrease of 38% in
      thyroglobulin levels in 23 patients. Cumulative survival rates were 78.5 +/- 8.4%
      at 5 years and 50.2 +/- 12.5% at 10 years (mean +/-SEM) after initial distant
      metastasectomy. CONCLUSIONS: Our data show that extensive targeted metastasectomy
      in the setting of a tertiary center can be beneficial to patients with
      disseminated ThyrCa with persistent or recurrent distant disease, when used in
      conjunction with nonsurgical treatment modalities.

PMID- 12501165
TI  - Prognostic significance of the size of cancer nests in metastatic lymph nodes in
      human esophageal cancers.
AB  - BACKGROUND: Postoperative survival of patients with esophageal cancers after
      curative surgery is strongly affected by the presence of lymph node metastasis.
      The number and location of lymph node metastases have been evaluated and graded,
      but the clinical significance of their size has not been well investigated.
      METHODS: Of 322 esophageal cancer patients who underwent curative operations with
      radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of
      784 metastatic lymph nodes were obtained, and the area of the cancer nests was
      measured microscopically in the cross section. The data from each patient
      included the area of the largest cancer nest in the positive nodes (Nmax),
      classified as Na (<4 mm2), Nb (4-25 mm2), Nc (25-100 mm2), or Nd (>100 mm2).
      RESULTS: The 170 patients were classified according to the Nmax value: Na, 31
      (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5-year survival
      rate was 77.7% in patients without lymph node metastasis and 35.4% in those with
      lymph node metastasis. When classified by Nmax, the 5-year survival rate was
      77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no
      significant difference in the survival rate between Na patients and those without
      lymph node metastasis. Nmax showed significant correlation with the primary tumor
      size, depth of tumor invasion, and number and location of metastatic lymph nodes,
      but not with histologic type or primary tumor location. In multivariate analysis,
      the Nmax value, the number of lymph node metastases and depth of tumor invasion
      were independent prognostic factors, while the location of the lymph node
      metastases was not statistically significant. CONCLUSIONS: The area of the
      largest cancer nest in the lymph nodes was one of the most significant prognostic
      factors for esophageal cancers. This estimation is objective and reproducible and
      may be of great importance when deciding the therapeutic modality for patients
      with esophageal cancers.

PMID- 12501166
TI  - Lymphocytic infiltration surrounding liver metastases from colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Tumor infiltrating lymphocytes (TILs) have been
      recognized as a tumor-host reaction in various primary neoplasms. Although
      several studies reported TILs surrounding metastatic liver tumors, to the
      authors' knowledge few evaluations of the clinical significance of such features
      in patients with colorectal liver metastases have been carried out. METHODS:
      Forty-one patients who underwent initial hepatic resection for liver metastases
      from colorectal cancer were studied. Lymphocytic infiltration surrounding
      metastatic liver tumor was graded as weak or dense according to the mean number
      of TILs from 10 high-power microscopic fields (< or =50 or >50/HPF). RESULTS:
      Dense lymphocytic infiltration between the metastatic tumor and hepatic
      parenchyma was seen in 18 of 41 patients (44%). Histologically, tumor invasion of
      the portal vein was rare in patients with dense TILs (12%) compared with patients
      with weak TILs (36%). Patients with dense TILs survived longer than patients with
      weak TILs after hepatic resection (P = 0.013). Multivariate analysis using the
      Cox proportional hazard model identified this pathological variable as a
      significant independent prognostic factor after hepatic resection. CONCLUSIONS:
      The extent of lymphocytic infiltration between the metastatic nodule and hepatic
      parenchyma may reflect host defensive activity in the liver and is closely
      related to prognosis in patients who underwent hepatic resection for liver
      metastases from colorectal cancer.

PMID- 12501167
TI  - Prognostic significance of biomarkers in squamous cell carcinoma of the tongue:
      multivariate analysis.
AB  - BACKGROUND AND OBJECTIVES: Expression of a panel of biomarkers, such as p53, Bcl
      2, Cyclin D1, c-myc, p21ras, c-erb B2, cytokeratin-19 (CK-19), and factor VIII
      related antigen (FVIII-RA), was studied together in anterior tongue tumors from
      the oral cavity and in posterior tongue tumors from the oropharynx of patients
      with early- and locally advanced-stage disease, to evaluate their prognostic
      value. METHODS: The expression of the above-mentioned biomarkers was studied by
      immunohistochemical localization. RESULTS: In this study, 18%, 26%, 62%, 75%,
      73%, 50%, and 29% of the tumors exhibited p53, Bcl-2, Cyclin D1, c-myc, p21ras, c
      erb B2, and CK-19 expression, respectively. Twenty percent of the tumors had a
      microvessel count of >0.0. The expression of these biomarkers was also correlated
      with clinicopathologic parameters. In early-stage patients with a tobacco habit,
      who showed borderline significance for relapse-free survival by Kaplan-Meier
      survival analysis, this turned out to be significant, with the general linear
      model univariate survival analysis. In the total group, disease stage emerged as
      the most significant prognostic factor, followed by c-myc, when Cox forward
      stepwise regression and general linear model multivariate survival analysis were
      performed. However, Cyclin D1, which was significant by Cox forward stepwise
      regression analysis, lost its significance by general linear model multivariate
      analysis. In patients with early-stage disease, MVC, which was a significant
      predictor of disease relapse by Cox forward stepwise regression analysis, lost
      its significance by general linear model analysis because of small number of
      patients. In patients with locally advanced tongue cancer, multivariate survival
      analysis of individual biomarkers by both Cox forward stepwise regression and
      general linear model analysis indicated c-myc expression to be strongly
      indicative of poor prognosis. However, multivariate analysis of individual
      markers along with a combination of markers showed that only by Cox forward
      stepwise regression analysis did the combined expression of markers c-myc, Cyclin
      D1, and p21ras emerge as a significant independent prognosticator. CONCLUSIONS:
      Overall stage emerged as the most significant prognostic indicator of disease
      outcome. Tobacco habit also affected relapse-free survival in patients with early
      stage disease. However, immunostaining of c-myc in the tumors of locally advanced
      stage tongue cancer patients might be a potential adjunct to clinical stage in
      the pathologic evaluation of tongue specimens.

PMID- 12501168
TI  - Enhancement of integrins by interleukin-1alpha, and their relationship with
      metastatic and invasive behavior of human pancreatic ductal adenocarcinoma cells.
AB  - BACKGROUND AND OBJECTIVES: Adhesion and invasion of tumor cells to extracellular
      matrix (ECM) proteins play an important role in tumor metastasis formation. We
      investigated the enhancement of adhesive and invasive behavior to ECM proteins of
      human pancreatic cancer cells by interleukin-1alpha (IL-1alpha) to examine the
      mechanism of adhesion and invasion of metastatic human pancreatic cancer cells to
      ECM proteins. METHODS: The enhancement of integrin subunits by IL-1alpha was
      examined by cellular enzyme-linked immunosorbent assay (CELISA) in two metastatic
      human pancreatic cancer cell lines (BxPC-3 and SW1990) and two nonmetastatic
      pancreatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer
      cell adhesion and invasion to ECM proteins were performed to investigate whether
      increased integrin expression affected the invasive interaction between cancer
      cells and the putative integrin ECM ligands. RESULTS: Expression of the alpha6
      subunit by metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer
      cells also exhibited preferential adherence and invasion to laminin compared with
      nonmetastatic cancer cells, and this was enhanced by IL-1alpha. CONCLUSIONS: The
      enhancement of alpha6beta1-integrin by Il-1alpha acting through IL-1RI, as well
      as the expression of alpha6beta1-integrin, plays an important role in metastasis
      formation in pancreatic cancer

PMID- 12501169
TI  - Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors.
AB  - BACKGROUND AND OBJECTIVES: Our objective was to identify differentially expressed
      genes involved in the pathogenesis of glioblastoma multiforme (GBM). METHODS:
      Screening of arrayed human fetal brain and human postnatal brain cDNA libraries
      was performed by differential hybridization with glioblastoma multiforme and
      human normal brain cDNAs. RESULTS: Repeated differential hybridization of more
      than 100 cDNA clones selected by primary screening and analysis of RNA from adult
      normal brain and glial tumors showed 16 nucleotide sequences differentially
      expressed between normal brain and brain tumors. Among others, decreased content
      in astrocytic tumors was determined for TSC-22 mRNA corresponding to cDNA in the
      ICRFp507J1041 clone from human fetal brain cDNA library. Northern blot
      hybridization of RNA from different human brain tumors showed very low amounts of
      TSC-22 mRNA in most investigated samples of GBM, anaplastic astrocytoma, and some
      other tumors. Complete lack of expression of TSC-22 occurred in one sample of
      anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous
      meningioma, and oligodendroglioma. The differential expression of TSC-22 gene was
      confirmed by semiquantitative RT-PCR in 15 samples of astrocytomas WHO grade II
      IV and three samples of normal brain. CONCLUSIONS: Significantly decreased levels
      of TSC-22 mRNA in human brain and salivary gland tumors and antiproliferative
      role of TSC-22 strongly suggest a tumor suppressor role for TSC-22. J.

PMID- 12501170
TI  - Regional chemotherapy is indicated after surgical resection of colorectal
      metastases to the liver: a debate.
AB  - Surgical resection for selected patients with hepatic metastases from colorectal
      cancer can cure approximately one-fourth of these patients. The addition of
      regional chemotherapy as an attempt to improve this statistic has been
      extensively investigated in clinical trials. As part of a multidisciplinary
      educational program, a series of debates on various topics in oncology are held
      at the Roswell Park Cancer Institute, Buffalo, New York, involving the medical,
      surgical, and radiation oncology departments. One such debate focused on the use
      of regional chemotherapy after potentially curative resection of hepatic
      metastases from colorectal cancer. The representative medical and surgical
      oncology fellows (N.I.K. and B.P.M.), with guidance from their respective mentors
      (C.G.L., J.F.G., and N.J.P.), presented concise reviews from the literature
      arguing for and against the use of regional chemotherapy in this setting. They
      appear as Parts 1 and 2 in this article. This exercise is purely educational and
      does not in any way reflect the opinion or the clinical practice of the authors.
      .

PMID- 12501171
TI  - Localization of nonpalpable breast lesions using hook-wire combined with
      isosulfan blue dye.

PMID- 12501172
TI  - Preoperative endoscopic clipping: localizing technique of early gastric cancer.

PMID- 12501173
TI  - The cyclooxygenase reaction mechanism.

PMID- 12501174
TI  - Histidine 407, a phantom residue in the E1 subunit of the Escherichia coli
      pyruvate dehydrogenase complex, activates reductive acetylation of lipoamide on
      the E2 subunit. An explanation for conservation of active sites between the E1
      subunit and transketolase.
AB  - Least squares alignment of the E. coli pyruvate dehydrogenase multienzyme complex
      E1 subunit and yeast transketolase crystal structures indicates a general
      structural similarity between the two enzymes and provides a plausible location
      for a short-loop region in the E1 structure that was unobserved due to disorder.
      The residue H407, located in this region, is shown to be able to penetrate the
      active site. Suggested by this comparison, the H407A E1 variant was created, and
      H407 was shown to participate in the reductive acetylation of both an
      independently expressed lipoyl domain and the intact 1-lipoyl E2 subunit. While
      the H407A substitution only modestly affected the reaction through pyruvate
      decarboxylation (ca. 14% activity compared to parental E1), the overall complex
      has a much impaired activity, at most 0.15% compared to parental E1. Isothermal
      titration calorimetry measurements show that the binding of the lipoyl domain to
      the H407A E1 variant is much weaker than that to parental E1. At the same time,
      mass spectrometric measurements clearly demonstrate much impaired reductive
      acetylation of the independently expressed lipoyl domain and of the intact 1
      lipoyl E2 by the H407A variant compared to the parental E1. A proposal is
      presented to explain the remarkable conservation of the three-dimensional
      structure at the active centers of the E. coli E1 subunit and transketolase on
      the basis of the parallels in the ligation-type reactions carried out and the
      need to protonate a very weak acid, a dithiolane sulfur atom in the former, and a
      carbonyl oxygen atom in the latter.

PMID- 12501175
TI  - The crystal structure of the H48Q active site mutant of human group IIA secreted
      phospholipase A2 at 1.5 A resolution provides an insight into the catalytic
      mechanism.
AB  - The human group IIA secreted PLA(2) is a 14 kDa calcium-dependent extracellular
      enzyme that has been characterized as an acute phase protein with important
      antimicrobial activity and has been implicated in signal transduction. The
      selective binding of this enzyme to the phospholipid substrate interface plays a
      crucial role in its physiological function. To study interfacial binding in the
      absence of catalysis, one strategy is to produce structurally intact but
      catalytically inactive mutants. The active site mutants H48Q, H48N, and H48A had
      been prepared for the secreted PLA(2)s from bovine pancreas and bee venom and
      retained minimal catalytic activity while the H48Q mutant showed the maximum
      structural integrity. Preparation of the mutant H48Q of the human group IIA
      enzyme unexpectedly produced an enzyme that retained significant (2-4%) catalytic
      activity that was contrary to expectations in view of the accepted catalytic
      mechanism. In this paper it is established that the high residual activity of the
      H48Q mutant is genuine, not due to contamination, and can be seen under a variety
      of assay conditions including assays in the presence of Co(2+) and Ni(2+) in
      place of Ca(2+). The crystallization of the H48Q mutant, yielding diffraction
      data to a resolution of 1.5 A, allowed a comparison with the corresponding
      recombinant wild-type enzyme (N1A) that was also crystallized. This comparison
      revealed that all of the important features of the catalytic machinery were in
      place and the two structures were virtually superimposable. In particular, the
      catalytic calcium ion occupied an identical position in the active site of the
      two proteins, and the catalytic water molecule (w6) was clearly resolved in the
      H48Q mutant. We propose that a variation of the calcium-coordinated oxyanion
      ("two water") mechanism involving hydrogen bonding rather than the anticipated
      full proton transfer to the histidine will best explain the ability of an active
      site glutamine to allow significant catalytic activity.

PMID- 12501176
TI  - Green fluorescent protein variants as ratiometric dual emission pH sensors. 1.
      Structural characterization and preliminary application.
AB  - Novel dual emission, pH-sensitive variants of the green fluorescent protein (GFP)
      have been constructed and are suitable for ratiometric emission measurements in
      vivo. This new class of GFPs, termed deGPFs, results from substitution of wild
      type residue 65 with threonine and residues 148 and/or 203 with cysteine. deGFPs
      display pK(a) values ranging from 6.8 to 8.0 and emission that switches from a
      green form (lambda(max) approximately 515 nm) to a blue form (lambda(max)
      approximately 460 nm) with acidifying pH. In this report we analyze in most
      detail the deGFP1 variant (S65T/H148G/T203C, pK(a) approximately 8.0) and the
      deGFP4 variant (S65T/C48S/H148C/T203C, pK(a) approximately 7.3). In the following
      paper [McAnaney, T. B., Park, E. S., Hanson, G. T., Remington, S. J., and Boxer,
      S. G. (2002) Biochemistry 41, 15489-15494], data obtained by ultrafast
      fluorescence upconversion spectroscopy can be described by a kinetic model that
      includes an excited-state proton-transfer pathway at high pH but not at low pH.
      Crystal structure analyses of deGFP1 at high-pH and low-pH conformations were
      performed to elucidate the basis for the dual emission characteristics. At low pH
      the structure does not contain a hydrogen bond network that would support rapid
      transfer of a proton from the excited state of the neutral chromophore to a
      suitable acceptor; hence blue emission is observed. At high pH, backbone
      rearrangements induced by changes in the associated hydrogen bond network permit
      excited-state proton transfer from the excited state of the neutral chromophore
      to the bulk solvent via Ser147 and bound water molecules, resulting in green
      emission from the anionic chromophore. Comparative analysis suggests that the
      basis for dual emission is elimination of the wild-type proton-transfer network
      by the S65T substitution, a general reduction in hydrogen-bonding opportunities,
      and a concomitant increase in the hydrophobic nature of the chromophore
      environment resulting from the cysteine substitutions. We evaluated the
      suitability of the deGFP4 variant for intracellular pH measurements in mammalian
      cells by transient expression in PS120 fibroblasts. The responses of deGFP4 and a
      commercially available pH-sensitive dye, SNARF-1, to changes in pH were compared
      in the same cells. Results show that the dynamic range of the emission ratio
      change is comparable between the two pH sensors over the range examined. Two
      photon excitation was found to elicit a better deGFP4 fluorescent signal above
      cellular autofluorescence when compared to conventional confocal microscopy.
      Given their favorable optical characteristics, suitable pK(a)'s for the
      physiological pH range, and suitability for ratiometric measurements, dual
      emission GFPs should make excellent probes for studying pH in vivo.

PMID- 12501177
TI  - Green fluorescent protein variants as ratiometric dual emission pH sensors. 2.
      Excited-state dynamics.
AB  - In the preceding paper [Hanson, G. T., McAnaney, T. B., Park, E. S., Rendell, M.
      E. P., Yarbrough, D. K., Chu, S., Xi, L., Boxer, S. G., Montrose, M. H., and
      Remington, S. J. (2002) Biochemistry 41, 15477-15488], novel mutants of the green
      fluorescent protein (GFP) that exhibit dual steady-state emission properties were
      characterized structurally and discussed as potential intracellular pH probes. In
      this work, the excited-state dynamics of one of these new dual emission GFP
      variants, deGFP4 (C48S/S65T/H148C/T203C), is studied by ultrafast fluorescence
      upconversion spectroscopy. Following excitation of the high-energy absorption
      band centered at 398 nm and assigned to the neutral form of the chromophore, time
      resolved emission was monitored from the excited state of both the neutral and
      intermediate anionic chromophores at both high and low pH and upon deuteration of
      exchangeable protons. The time-resolved emission dynamics and isotope effect
      appear to be very different from those of wild-type GFP [Chattoraj, M., King, B.
      A., Bublitz, G. U., and Boxer, S. G. (1996) Proc. Natl. Acad. Sci. U.S.A. 93,
      8362-8367]; however, due to overlapping emission bands, the apparent difference
      can be analyzed quantitatively within the same framework used to describe GFP
      excited-state dynamics. The results indicate that the pH-sensitive steady-state
      emission characteristics of deGFP4 are a result of a pH-dependent modulation of
      the rate of excited-state proton transfer. At high pH, a rapid interconversion
      from the excited state of the higher energy neutral chromophore to the lower
      energy intermediate anionic chromophore is achieved by proton transfer. At low
      pH, excited-state proton transfer is slowed to the point where it is no longer
      rate limiting.

PMID- 12501178
TI  - Conformational analysis of intermediates involved in the in vitro folding
      pathways of recombinant human macrophage colony stimulating factor beta by
      sulfhydryl group trapping and hydrogen/deuterium pulsed labeling.
AB  - In vitro oxidative folding of reduced recombinant human macrophage colony
      stimulating factor beta (rhm-CSFbeta) involves two major events: disulfide
      isomerization in the monomeric intermediates and disulfide-mediated dimerization.
      Kinetic analysis of rhm-CSFbeta folding indicated that monomer isomerization is
      slower than dimerization and is, in fact, the rate-determining step. A time
      dependent determination of the number of free cysteines remaining was made after
      refolding commence. The folding intermediates revealed that rhm-CSFbeta folds
      systematically, forming disulfide bonds via multiple pathways. Mass spectrometric
      evidence indicates that native as well as non-native intrasubunit disulfide bonds
      form in monomeric intermediates. Initial dimerization is assumed to involve
      formation of disulfide bonds, Cys 157/159-Cys' 157/159. Among six intrasubunit
      disulfide bonds, Cys 48-Cys 139 and Cys' 48-Cys' 139 are assumed to be the last
      to form, while Cys 31-Cys' 31 is the last intersubunit disulfide bond that forms.
      Conformational properties of the folding intermediates were probed by H/D
      exchange pulsed labeling, which showed the coexistence of noncompact dimeric and
      monomeric species at early stages of folding. As renaturation progresses, the
      noncompact dimer undergoes significant structural rearrangement, forming a native
      like dimer while the monomer maintains a noncompact conformation.

PMID- 12501179
TI  - Structural insights into the avian AICAR transformylase mechanism.
AB  - ATIC encompasses both AICAR transformylase and IMP cyclohydrolase activities that
      are responsible for the catalysis of the penultimate and final steps of the
      purine de novo synthesis pathway. The formyl transfer reaction catalyzed by the
      AICAR Tfase domain is substantially more demanding than that catalyzed by the
      other folate-dependent enzyme of the purine biosynthesis pathway, GAR
      transformylase. Identification of the AICAR Tfase active site and key catalytic
      residues is essential to elucidate how the non-nucleophilic AICAR amino group is
      activated for formyl transfer. Hence, the crystal structure of dimeric avian ATIC
      was determined as a complex with the AICAR Tfase substrate AICAR, as well as with
      an IMP cyclohydrolase inhibitor, XMP, to 1.93 A resolution. AICAR is bound at the
      dimer interface of the transformylase domains and forms an extensive hydrogen
      bonding network with a multitude of active site residues. The crystal structure
      suggests that the conformation of the 4-carboxamide of AICAR is poised to
      increase the nucleophilicity of the C5 amine, while proton abstraction occurs via
      His(268) concomitant with formyl transfer. Lys(267) is likely to be involved in
      the stabilization of the anionic formyl transfer transition state and in
      subsequent protonation of the THF leaving group.

PMID- 12501180
TI  - Crystal structures of two potent nonamidine inhibitors bound to factor Xa.
AB  - There has been intense interest in the development of factor Xa inhibitors for
      the treatment of thrombotic diseases. Our laboratory has developed a series of
      novel non-amidine inhibitors of factor Xa. This paper presents two crystal
      structures of compounds from this series bound to factor Xa. The first structure
      is derived from the complex formed between factor Xa and compound 1. Compound 1
      was the first non-amidine factor Xa inhibitor from our lab that had measurable
      potency in an in vitro assay of anticoagulant activity. The second compound, 2,
      has a molar affinity for factor Xa (K(iapp)) of 7 pM and good bioavailability.
      The two inhibitors bind in an L-shaped conformation with a chloroaromatic ring
      buried deeply in the S1 pocket. The opposite end of these compounds contains a
      basic substituent that extends into the S4 binding site. A chlorinated phenyl
      ring bridges the substituents in the S1 and S4 pockets via amide linkers. The
      overall conformation is similar to the previously published structures for
      amidine-based inhibitors complexed with factor Xa. However, there are significant
      differences in the interactions between the inhibitor and the protein at the
      atomic level. Most notably, there is no group that forms a salt bridge with the
      carboxylic acid at the base of the S1 pocket (Asp189). Each inhibitor forms only
      one well-defined hydrogen bond to the protein. There are no direct charge-charge
      interactions. The results indicate that electrostatic interactions play a
      secondary role in the binding of these potent inhibitors.

PMID- 12501181
TI  - Structural and thermodynamic studies on a salt-bridge triad in the NADP-binding
      domain of glutamate dehydrogenase from Thermotoga maritima: cooperativity and
      electrostatic contribution to stability.
AB  - Cooperative interactions within ion-pair networks of hyperthermostable proteins
      are thought to be a major determinant for extreme protein stability. While the
      favorable thermodynamic contributions of optimized electrostatics in general as
      well as those of pairwise interactions have been documented, cooperativity
      between pairwise interactions has not yet been studied thermodynamically in
      proteins from hyperthermophiles. In this study we use the isolated cofactor
      binding domain of glutamate dehydrogenase from the hyperthermophilic bacterium
      Thermotoga maritima to analyze pairwise and cooperative interactions within the
      salt-bridge triad Arg190-Glu231-Lys193. The X-ray structure of the domain was
      solved at 1.43 A and reveals the salt-bridge network with surrounding solvent
      molecules in detail. All three participating charges in the network were mutated
      to alanine in all combinations. The X-ray structure of the variant lacking all
      three charges reveals that the removal of the side chains has no effect on the
      overall conformation of the protein. Using solvent denaturation and thermodynamic
      cycles, the interaction energies between each pair of residues in the network
      were determined in the presence and in the absence of the third residue. Both the
      Arg190-Glu231 ion pair and the Lys193-Glu231 salt bridge in the absence of the
      third residue, contribute favorably to the free energy for unfolding of the
      domain in urea. Using guanidinium chloride as denaturant reveals a strong
      cooperativity between the two ion-pair interactions, the presence of the second
      ion pair converts the first interaction from destabilizing into stabilizing by as
      much as 1.09 kcal/mol. The different energetics of the salt-bridge triad in urea
      and GdmCl are discussed with reference to the observed anion binding in the
      crystal structure at high ionic strength and their possible role in a highly
      charged, high-temperature environment such as the cytoplasm of hyperthermophiles.

PMID- 12501182
TI  - The solution structure of apocalmodulin from Saccharomyces cerevisiae implies a
      mechanism for its unique Ca2+ binding property.
AB  - We have determined the solution structure of calmodulin (CaM) from yeast
      (Saccharomyces cerevisiae) (yCaM) in the apo state by using NMR spectroscopy.
      yCaM is 60% identical in its amino acid sequence with other CaMs, and exhibits
      its unique biological features. yCaM consists of two similar globular domains (N-
      and C-domain) containing three Ca(2+)-binding motifs, EF-hands, in accordance
      with the observed 3 mol of Ca(2+) binding. In the solution structure of yCaM, the
      conformation of the N-domain conforms well to the one of the expressed N-terminal
      half-domains of yCaM [Ishida, H., et al. (2000) Biochemistry 39, 13660-13668].
      The conformation of the C-domain basically consists of a pair of helix-loop-helix
      motifs, though a segment corresponding to the forth Ca(2+)-binding site of CaM
      deviates in its primary structure from a typical EF-hand motif and loses the
      ability to bind Ca(2+). Thus, the resulting conformation of each domain is
      essentially identical to the corresponding domain of CaM in the apo state. A
      flexible linker connects the two domains as observed for CaM. Any evidence for
      the previously reported interdomain interaction in yCaM was not observed in the
      solution structure of the apo state. Hence, the interdomain interaction possibly
      occurs in the course of Ca(2+) binding and generates a cooperative Ca(2+) binding
      among all three sites. Preliminary studies on a mutant protein of yCaM, E104Q,
      revealed that the Ca(2+)-bound N-domain interacts with the apo C-domain and
      induces a large conformational change in the C-domain.

PMID- 12501183
TI  - The catalytic cycle of biosynthetic thiolase: a conformational journey of an
      acetyl group through four binding modes and two oxyanion holes.
AB  - Biosynthetic thiolase catalyzes the formation of acetoacetyl-CoA from two
      molecules of acetyl-CoA. This is a key step in the synthesis of many biological
      compounds, including steroid hormones and ketone bodies. The thiolase reaction
      involves two chemically distinct steps; during acyl transfer, an acetyl group is
      transferred from acetyl-CoA to Cys89, and in the Claisen condensation step, this
      acetyl group is further transferred to a second molecule of acetyl-CoA,
      generating acetoacetyl-CoA. Here, new crystallographic data for Zoogloea ramigera
      biosynthetic thiolase are presented, covering all intermediates of the thiolase
      catalytic cycle. The high-resolution structures indicate that the acetyl group
      goes through four conformations while being transferred from acetyl-CoA via the
      acetylated enzyme to acetoacetyl-CoA. This transfer is catalyzed in a rigid
      cavity lined by mostly hydrophobic side chains, in addition to the catalytic
      residues Cys89, His348, and Cys378. The structures highlight the importance of an
      oxyanion hole formed by a water molecule and His348 in stabilizing the negative
      charge on the thioester oxygen atom of acetyl-CoA at two different steps of the
      reaction cycle. Another oxyanion hole, composed of the main chain nitrogen atoms
      of Cys89 and Gly380, complements a negative charge of the thioester oxygen anion
      of the acetylated intermediate, stabilizing the tetrahedral transition state of
      the Claisen condensation step. The reactivity of the active site may be modulated
      by hydrogen bonding networks extending from the active site toward the back of
      the molecule.

PMID- 12501184
TI  - Biochemical and structural characterization of the cross-linked complex of
      nitrogenase: comparison to the ADP-AlF4(-)-stabilized structure.
AB  - The transient formation of a complex between the component Fe- and MoFe-proteins
      of nitrogenase represents a central event in the substrate reduction mechanism of
      this enzyme. Previously, we have isolated an N-[3-(dimethylamino)propyl]-N'
      ethylcarbodiimide (EDC) cross-linked complex of these proteins stabilized by a
      covalent isopeptide linkage between Glu 112 and Lys beta400 of the Fe-protein and
      MoFe-protein, respectively [Willing, A., et al. (1989) J. Biol. Chem. 264, 8499
      8503; Willing, A., and Howard, J. B. (1990) J. Biol. Chem. 265, 6596-6599]. We
      report here the biochemical and structural characterization of the cross-linked
      complex to assess the mechanistic relevance of this species. Glycinamide inhibits
      the cross-linking reaction, and is found to be specifically incorporated into Glu
      112 of the Fe-protein, without detectable modification of either of the
      neighboring residues (Glu 110 and Glu 111). This modified protein is still
      competent for substrate reduction, demonstrating that formation of the cross
      linked complex is responsible for the enzymatic inactivation, and not the EDC
      reaction or the modification of the Fe-protein. Crystallographic analysis of the
      EDC-cross-linked complex at 3.2 A resolution confirms the site of the isopeptide
      linkage. The nature of the protein surfaces around the cross-linking site
      suggests there is a strong electrostatic component to the formation of the
      complex, although the interface area between the component proteins is small. The
      binding footprints between proteins in the cross-linked complex are adjacent, but
      with little overlap, to those observed in the complex of the nitrogenase proteins
      stabilized by ADP-AlF(4)(-). The results of these studies suggest that EDC cross
      linking traps a nucleotide-independent precomplex of the nitrogenase proteins
      driven by complementary electrostatic interactions that subsequently rearranges
      in a nucleotide-dependent fashion to the electron transfer competent state
      observed in the ADP-AlF(4)(-) structure.

PMID- 12501185
TI  - Interactions of the products, 8-oxo-dGMP, dGMP, and pyrophosphate with the MutT
      nucleoside triphosphate pyrophosphohydrolase.
AB  - The MutT enzyme from E. coli, in the presence of a divalent cation, catalyzes the
      hydrolysis of nucleoside- and deoxynucleoside-triphosphate (NTP) substrates by
      nucleophilic substitution at Pbeta, to yield a nucleotide (NMP) and PPi. The best
      substrate of MutT is believed to be the mutagenic nucleotide 8-oxo-dGTP, on the
      basis of its 10(3.4)-fold lower K(m) than that of dGTP (Maki, H., and Sekiguchi,
      M. (1992) Nature 355, 273-275). To determine the true affinity of MutT for an 8
      oxo-nucleotide and to elucidate the kinetic scheme, product inhibition by 8-oxo
      dGMP and dGMP and direct binding of these nucleotides to MutT were studied. With
      Mg(2+)-activated dGTP hydrolysis, 8-oxo-dGMP is a noncompetitive inhibitor with
      K(I)(sl)(o)(pe) = 49 nM, which is 10(4.6)-fold lower than the K(I)(sl)(o)(pe)of
      dGMP (1.7 mM). Similarly, the K(I)(intercept) of 8-oxo-dGMP is 10(4.0)-fold lower
      than that of dGMP. PPi is a linear uncompetitive inhibitor, suggesting that it
      dissociates first from the product complex, followed by the nucleotide.
      Noncompetitive inhibition by dGMP and 8-oxo-dGMP indicates an "iso" mechanism in
      which the nucleotide product leaves an altered form of the enzyme which slowly
      reverts to the form which binds substrate. Consistent with this kinetic scheme,
      (1)H-(15)N HSQC titration of MutT with dGMP reveals weak binding and fast
      exchange from one site with a K(D) = 1.8 mM, in agreement with its
      K(I)(sl)(o)(pe). With 8-oxo-dGMP, tight binding and slow exchange (n = 1.0 +/-
      0.1, K(D) < 0.25 mM) are found. Isothermal calorimetric titration of MutT with 8
      oxo-dGMP yields a K(D) of 52 nM, in agreement with its K(I)(sl)(o)(pe). Changing
      the metal activator from Mg(2+) to Mn(2+) had little effect on the
      K(I)(sl)(o)(pe) of dGMP or of 8-oxo-dGMP, consistent with the second-sphere
      enzyme-M(2+)-H(2)O-NTP-M(2+) complex found by NMR (Lin, J., Abeygunawardana, C.,
      Frick, D. N., Bessman, M. J., and Mildvan, A. S. (1997) Biochemistry 36, 1199
      1211), but it decreased the K(I) of PPi 12-fold, suggesting direct coordination
      of the PPi product by the enzyme-bound divalent cation. The tight binding of 8
      oxo-dGMP to MutT (DeltaG degrees = -9.8 kcal/mol) is driven by a highly favorable
      enthalpy (<DeltaH(binding)> = -32 +/- 7 kcal/mol), with an unfavorable entropy (<
      TDeltaS(o)(binding)> = +22 +/- 7 kcal/mol), as determined by van't Hoff analysis
      of the effect of temperature on the K(I)(sl)(o)(pe) and by isothermal titration
      calorimetry in two buffer systems. The binding of 8-oxo-dGMP to MutT induces
      changes in backbone (15)N and NH chemical shifts of 62 residues widely
      distributed throughout the protein, while dGMP binding induces smaller changes in
      only 22 residues surrounding the nucleotide binding site, suggesting that the
      unusually high affinity of MutT for 8-oxo-nucleotides is due not only to
      interactions with the altered 8-oxo or 7-NH positions on guanine, but results
      primarily from diffuse structural changes which tighten the protein structure
      around the 8-oxo-nucleotide.

PMID- 12501186
TI  - Structure of the MUR1 GDP-mannose 4,6-dehydratase from Arabidopsis thaliana:
      implications for ligand binding and specificity.
AB  - GDP-D-mannose 4,6-dehydratase catalyzes the first step in the de novo synthesis
      of GDP-L-fucose, the activated form of L-fucose, which is a component of
      glycoconjugates in plants known to be important to the development and strength
      of stem tissues. We have determined the three-dimensional structure of the MUR1
      dehydratase isoform from Arabidopsis thaliana complexed with its NADPH cofactor
      as well as with the ligands GDP and GDP-D-rhamnose. MUR1 is a member of the
      nucleoside-diphosphosugar modifying subclass of the short-chain
      dehydrogenase/reductase enzyme family, having homologous structures and a
      conserved catalytic triad of Lys, Tyr, and Ser/Thr residues. MUR1 is the first
      member of this subfamily to be observed as a tetramer, the interface of which
      reveals a close and intimate overlap of neighboring NADP(+)-binding sites. The
      GDP moiety of the substrate also binds in an unusual syn conformation. The
      protein-ligand interactions around the hexose moiety of the substrate support the
      importance of the conserved triad residues and an additional Glu side chain
      serving as a general base for catalysis. Phe and Arg side chains close to the
      hexose ring may serve to confer substrate specificity at the O2 position. In the
      MUR1/GDP-D-rhamnose complex, a single unique monomer within the protein tetramer
      that has an unoccupied substrate site highlights the conformational changes that
      accompany substrate binding and may suggest the existence of negative
      cooperativity in MUR1 function.

PMID- 12501187
TI  - Characterization and mutagenesis of Gal/GlcNAc-6-O-sulfotransferases.
AB  - The installation of sulfate groups on the carbohydrate residues of glycoproteins,
      glycolipids, and glycosaminoglycans is a critical posttranslational modification
      that occurs in all higher eukaryotes. The Gal/GalNAc/GlcNAc-6-O-sulfotransferases
      (GSTs) are a recently discovered family of carbohydrate sulfotransferases that
      share significant sequence homology at the amino acid level and mediate a number
      of different biological processes such as leukocyte adhesion at sites of chronic
      inflammation. Structural and mechanistic studies of this family of
      sulfotransferases have been hindered by the lack of a productive recombinant
      protein expression system. We developed a baculovirus expression system for five
      of the seven cloned GSTs and determined their kinetic parameters using both thin
      layer chromatography and a recently developed polymer dot-blot assay. We used
      these tools to perform the first site-directed mutagenesis study of a member of
      this sulfotransferase family, GST2. Using sequence alignments with other
      carbohydrate and cytosolic sulfotransferases, we selected residues within the
      putative binding regions for 3'-phosphoadenosine 5'-phosphosulfate (PAPS) and the
      carbohydrate substrate for mutagenesis. Kinetic analysis of the mutants
      identified residues that are essential for catalytic activity. These results
      should facilitate mechanistic studies and the development of small molecule
      inhibitors of this enzyme family to ameliorate chronic inflammatory diseases.

PMID- 12501188
TI  - Kinetic and spectroscopic studies of Tritrichomonas foetus low-molecular weight
      phosphotyrosyl phosphatase. Hydrogen bond networks and electrostatic effects.
AB  - Virtually all of the eukaryotic low-molecular weight protein tyrosine
      phosphatases (LMW PTPases) studied to date contain a conserved, high-pK(a)
      histidine residue that is hydrogen bonded to a conserved active site asparagine
      residue of the phosphate binding loop. However, in the putative enzyme encoded by
      the genome of the trichomonad parasite Tritrichomonas foetus, this otherwise
      highly conserved histidine is replaced with a glutamine residue. We have cloned
      the gene, expressed the enzyme, demonstrated its catalytic activity, and examined
      the structural and functional roles of the glutamine residue using site-directed
      mutagenesis, kinetic measurements, and NMR spectroscopy. Titration studies of the
      two native histidine residues in the T. foetus enzyme as monitored by (1)H NMR
      revealed that H44 has a pK(a) of 6.4 and H143 has a pK(a) of 5.3. When a
      histidine residue was introduced in place of the native glutamine at position 67,
      a pK(a) of 8.2 was measured for this residue. Steady state kinetic methods were
      employed to study how mutation of the native glutamine to alanine, asparagine,
      and histidine affected the catalytic activity of the enzyme. Examination of
      k(cat)/K(m) showed that Q67H exhibits a substrate selectivity comparable to that
      of the wild-type (WT) enzyme, while Q67N and Q67A show reduced activity. The
      effect of pH on the reaction rate was examined. Importantly, the pH-rate profile
      of the WT TPTP enzyme revealed a much more clearly defined acidic limb than that
      which can be observed for other wild-type LMW PTPases. The pH-rate curve of the
      Q67H mutant shows a shift to a lower pH optimum relative to that seen for the
      wild-type enzyme. The Q67N and Q67A mutants showed curves that were shifted to
      higher pH optima. Although the active site of this enzyme is likely to be similar
      to that of other LMW PTPases, the hydrogen bonding and electrostatic changes
      afford new insight into factors affecting the pH dependence and catalysis by this
      family of enzymes.

PMID- 12501189
TI  - The crystal structure of fragment double-D from cross-linked lamprey fibrin
      reveals isopeptide linkages across an unexpected D-D interface.
AB  - The crystal structure of fragment double-D from factor XIII-cross-linked lamprey
      fibrin has been determined at 2.9 A resolution. The 180 kDa covalent dimer was
      cocrystallized with the peptide Gly-His-Arg-Pro-amide, which in many fibrinogens,
      but not that of lamprey, corresponds to the B-knob exposed by thrombin. The
      structure was determined by molecular replacement, a recently determined
      structure of lamprey fragment D being used as a search model. GHRPam was found in
      both the gamma- and beta-chain holes. Unlike the situation with fragment D, the
      crystal packing of the cross-linked double-D structure exhibits two different D-D
      interfaces, each gamma-chain facing gamma-chains on two other molecules. One of
      these (interface I) involves the asymmetric interface observed in all other D
      fragments and related structures. The other (interface II) encompasses a
      completely different set of residues. The two abutments differ in that interface
      I results in an "in line" arrangement of abutting molecules and the interface II
      in a "zigzag" arrangement. So far as can be determined (the electron density
      could only be traced on one side of the cross-links), it is the gamma-chains of
      the newly observed zigzag units (interface II) that are joined by the reciprocal
      epsilon-amino-gamma-glutamyl cross-links. Auspiciously, the same novel D-D
      interface was observed in two lower-resolution crystal structures of human double
      D preparations that had been crystallized under unusual circumstances. These
      observations show that double-D structures are linked in a way that is
      sufficiently flexible to accommodate different D-D interfaces under different
      circumstances.

PMID- 12501190
TI  - Characterization of the monomeric form of the transmembrane and cytoplasmic
      domains of the integrin beta 3 subunit by NMR spectroscopy.
AB  - We have characterized a membrane protein containing residues P688-T762 of the
      integrin beta3 subunit, encompassing its transmembrane and cytoplasmic domains,
      by nuclear magnetic resonance spectroscopy. Under conditions in which it is
      monomeric in dodecylphosphocholine micelles, the protein consists mainly of alpha
      helical structures. An amino-terminal helix corresponding to the beta3
      transmembrane helix extends into the membrane-proximal region of the cytoplasmic
      domain. Moreover, following an apparent hinge at residues H722-D723, residues
      K725-A735 are mostly alpha-helical. In the presence of membrane-mimicking
      detergents, the cytoplasmic domain connected to the transmembrane helix is
      substantially ordered at pH 4.8 and 50 degrees C. Its carboxyl-terminal end takes
      on a turn-helix configuration characteristic of the immunoreceptor tyrosine-based
      activation motif. These structural features of the beta3 subunit should help to
      explain its interaction with numerous cytosolic interacting proteins and begin to
      illuminate the mechanism of integrin activation.

PMID- 12501191
TI  - Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A.
AB  - Progression through S phase of the eukaryotic cell cycle is regulated by the
      action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin
      A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often
      employs a dual recognition strategy in which the sequence flanking the phospho
      acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A
      component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu
      ("RXL" or "KXL") substrate recruitment motifs. To determine additional sequence
      specificity motifs around the RXL sequence, we have performed X-ray
      crystallographic studies at 2.3 A resolution and isothermal calorimetry
      measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide
      derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and
      p107. The results show that the cyclin recruitment site accommodates a second
      hydrophobic residue either immediately C-terminal or next adjacent to the leucine
      of the "RXL" motif and that this site makes important contributions to the
      recruitment peptide recognition. The arginine of the RXL motif contacts a
      glutamate, Glu220, on the cyclin. In those substrates that contain a KXL motif,
      no ionic interactions are observed with the lysine. The sequences N-terminal to
      the "RXL" motif of the individual peptides show no conservation, but nevertheless
      make common contacts to the cyclin through main chain interactions. Thus, the
      recruitment site is able to recognize diverse but conformationally constrained
      target sequences. The observations have implications for the further
      identification of physiological substrates of CDK2/cyclin A and the design of
      specific inhibitors.

PMID- 12501192
TI  - Mechanism of activation and selectivity in a ligand-gated ion channel: structural
      and functional studies of GluR2 and quisqualate.
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian brain. The
      (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole)propionic acid (AMPA)-subtype
      glutamate receptor, a ligand-gated ion channel, mediates most of the fast
      excitatory synaptic transmission in the mammalian central nervous system. Here we
      present electrophysiological, biochemical, and crystallographic data on the
      interactions between quisqualate and the GluR2 receptor ion channel and its
      corresponding ligand binding core. Quisqualate is a high-affinity, full agonist
      which like AMPA and glutamate elicits maximum peak current responses, and
      stabilizes the ligand binding core in a fully closed conformation, reinforcing
      the concept that full agonists produce similar conformational changes [Armstrong,
      N., and Gouaux, E. (2000) Neuron 28, 165-181]. Nevertheless, the mechanism of
      quisqualate binding is different from that of AMPA but similar to that of
      glutamate, illustrating that quisqualate is a faithful glutamate analogue. A
      detailed comparison of the three agonist complexes reveals distinct binding
      mechanisms, particularly in the region of a hydrophobic pocket that is proximal
      to the anionic gamma-substituents, and demonstrates the importance of agonist
      water-receptor interactions. The hydrophobic pocket, which is predicted to vary
      in chemical character between receptor subtypes, probably plays an important role
      in determining receptor subtype specificity.

PMID- 12501193
TI  - Understanding the catalytic mechanism of GTPase-activating proteins:
      demonstration of the importance of switch domain stabilization in the stimulation
      of GTP hydrolysis.
AB  - Cdc42, a member of the Rho family of GTP-binding proteins, has been implicated in
      a variety of biological activities, including the organization of the actin
      cytoskeleton, changes in cell morphology and motility, intracellular trafficking,
      cell cycle progression, and cellular transformation. The cycling of Cdc42 between
      its on (GTP-bound) and off (GDP-bound) states is essential for its stimulation of
      cell growth and transformation, with an important aspect of this cycle being the
      regulation of the GTP hydrolytic activity of Cdc42 by its GTPase-activating
      protein (Cdc42GAP). On the basis of the structural determinations of the Cdc42
      Cdc42GAP complex, as well as the Ras-RasGAP complex, it has been proposed that an
      arginine residue provided by the GAP (called the "arginine finger") stabilizes
      charges developing on the guanine nucleotide during the transition state for GTP
      hydrolysis and is an important contributor to GAP-stimulated catalysis. However,
      the 85 kDa regulatory subunit (p85) of the phosphoinositide 3-kinase (PI-3K) is
      homologous with the Cdc42GAP and contains the essential arginine residue, but is
      ineffective as a GAP. This argues that the introduction of the arginine finger is
      insufficient for GAP activity and that the GAP must fulfill an additional
      function, one possibility being the engagement and stabilization of the
      conformationally sensitive switch regions of Cdc42. In the study presented here,
      we have tested this idea by examining three residues within the Cdc42GAP, which
      are missing in the GAP homology domain of the 85 kDa regulatory subunit (p85) of
      the PI 3-kinase and are involved in specific interactions with switch domain
      residues of Cdc42. We show that the mutation of all three residues, as well as
      individual mutations of each of these residues, yields GAPs that are defective in
      stimulating GTP hydrolysis. We further demonstrate that the switch I residue
      tyrosine 32 plays an important role in GAP interactions and in the regulation of
      both intrinsic and GAP-stimulated GTP hydrolysis. Taken together, these findings
      indicate that stabilizing the switch domains of GTP-binding proteins is an
      important part of GAP-stimulated catalysis, and that the inability of p85 to
      participate in these interactions may at least in part explain its
      ineffectiveness as a GAP.

PMID- 12501194
TI  - The solution structure of a cardiac troponin C-troponin I-troponin T complex
      shows a somewhat compact troponin C interacting with an extended troponin I
      troponin T component.
AB  - We have investigated the structure of the cTnC-cTnI-cTnT(198-298) calcium
      saturated, ternary cardiac troponin complex by small-angle scattering with
      contrast variation. Shape restoration was also applied to the scattering
      information resulting from the deuterated cTnC subunit, the unlabeled cTnI
      cTnT(198-298) subunits, and the entire complex. The experimental results and
      modeling indicate that cTnC adopts a partially collapsed conformation, while the
      cTnI-cTnT(198-298) components have an extended, rod-like structure. Shape
      restoration applied to the X-ray scattering data and the entire contrast
      variation series suggest that cTnC and the cTnI-cTnT(198-298) component lie with
      their long axes roughly parallel to one another with a relatively small surface
      area for interaction. Our findings indicate that the nature of the interactions
      between TnC and the TnI-TnT component differs significantly between the cardiac
      and skeletal isoforms as evidenced by the different degrees of compactness
      between the cardiac TnC and skeletal TnC in their respective ternary complexes
      and the fact that the cTnC subunit is not highly intertwined with the other
      subunits, as observed in the binary complex of the skeletal isoforms [Olah, G.
      A., and Trewhella, J. (1994) Biochemistry 33, 12800-12806].

PMID- 12501195
TI  - Breaking symmetry: mutations engineered into R67 dihydrofolate reductase, a D2
      symmetric homotetramer possessing a single active site pore.
AB  - R67 dihydrofolate reductase (DHFR) is an enzyme, encoded by an R-plasmid, that
      confers resistance to the antibacterial agent trimethoprim. This homotetramer
      possesses a single active site pore and exact 222 symmetry. The symmetry imposes
      constraints on the ability of the enzyme to optimize binding of the substrate,
      dihydrofolate (DHF), and the cofactor, NADPH, resulting in a "one site fits both
      ligands" approach. This approach allows formation of either a NADPH.NADPH,
      dihydrofolate.dihydrofolate, or NADPH.dihydrofolate complex. The first two
      complexes are nonproductive, while the third is the productive catalytic species.
      To break the symmetry of the active site, a tandem array of four R67 DHFR genes
      has been linked in frame, allowing individual manipulation of each gene copy.
      Various numbers and combinations of asymmetric Q67H mutations have been
      engineered into the tandem gene array. The Q67H mutation was chosen for
      investigation as it was previously found to tighten binding to both dihydrofolate
      and NADPH by approximately 100-fold in homotetrameric R67 DHFR [Park, H.,
      Bradrick, T. D., and Howell, E. E. (1997) Protein Eng. 10, 1415-1424].
      Nonadditive effects on ligand binding are observed when one to four mutations are
      inserted, indicating either conformational changes in the protein or different
      cooperativity patterns in the ligand-ligand interactions. From steady state
      kinetics, addition of Q67H mutations does not drastically affect formation of the
      NADPH.dihydrofolate complex; however, a large energy difference between the
      productive and nonproductive complexes is no longer maintained. A role for Q67 in
      discriminating between these various states is proposed. Since theories of
      protein evolution suggest gene duplication followed by accumulation of mutations
      can lead to divergence of activity, this study is a first step toward asking if
      introduction of asymmetric mutations in the quadrupled R67 DHFR gene can lead to
      optimization of ligand binding sites.

PMID- 12501196
TI  - Probing backbone hydrogen bonds in the hydrophobic core of GCN4.
AB  - Backbone amide hydrogen bonds play a central role in protein secondary and
      tertiary structure. Previous studies have shown that substitution of a backbone
      ester (-COO-) in place of a backbone amide (-CONH-) can selectively destabilize
      backbone hydrogen bonds in a protein while maintaining a similar conformation to
      the native backbone structure. The majority of these studies have focused on
      backbone substitutions that were accessible to solvent. The GCN4 coiled coil
      domain is an example of a stable alpha-helical dimer that possesses a well-packed
      hydrophobic core. Amino acids in the a and d positions of the GCN4 helix, which
      pack the hydrophobic core, were replaced with the corresponding alpha-hydroxy
      acids in the context of a chemoselectively ligated heterodimer. While the overall
      structure and oligomerization state of the heterodimer were maintained, the
      overall destabilization of the ester analogues was greater (average DeltaDeltaG
      of 3+ kcal mol(-1)) and more variable than previous studies. Since burial of the
      more hydrophobic ester should stabilize the backbone and reduce the DeltaDeltaG,
      the increased destabilization must come from another source. However, the
      observed destabilization is correlated with the protection factors for individual
      amide hydrogens from previous hydrogen exchange experiments. Therefore, our
      results suggest that backbone engineering through ester substitution is a useful
      approach for probing the relative strength of backbone hydrogen bonds.

PMID- 12501197
TI  - Substitution of conserved hydrophobic residues in motifs B and C of HIV-1 RT
      alters the geometry of its catalytic pocket.
AB  - Recent crystallographic data suggest that a number of hydrophobic residues seen
      clustered between the structurally conserved alphabetabetaalpha motif of the palm
      subdomain and at the junction of palm and fingers subdomains of human
      immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) provide an optimal
      geometry to the alphabeta sandwich of the palm subdomain, which harbors the
      catalytic site and the primer-binding grip region. This region has also been
      implicated in binding to the non-nucleoside RT inhibitors. We have evaluated the
      impact of conserved and nonconserved amino acid substitutions at four hydrophobic
      positions in this region of HIV-1 RT, in the context of their biochemical
      characteristics. The residues that have been analyzed include Ile-167, Leu-187,
      and Val-189 which are located within the alphabetabetaalpha motif, while Trp-153
      lies next to the conserved LPQG motif, at the juncture of the palm and fingers
      subdomains. Our results show that all substitutions at I167 with the exception of
      I167T were deleterious to enzyme function in contrast to substitutions at V189
      which enhanced the enzymatic activity. Ala substitution at residues W153 and L187
      also substantially hindered the polymerase function of the enzyme. Further
      analysis revealed that the defective mutant derivatives of I167 were
      substantially impaired in their apparent dNTP binding abilities, thereby
      impacting the geometry of the dNTP binding pocket. The extent of misinsertion and
      misincorporation was higher in the case of RT variants of W153 and V189,
      specifically on a DNA template. Interestingly, none of the mutant derivatives of
      these residues were resistant to nucleoside inhibitors. A salient finding was
      that all nonconserved mutants of these residues exhibited hypersensitivity to
      nevirapine. We have analyzed these findings and their significance in the context
      of the HIV-1 RT structure and propose that these residues exert their effect via
      their indirect interactions with the template-primer through residues in their
      vicinity.

PMID- 12501198
TI  - Plastocyanin-cytochrome f interactions: the influence of hydrophobic patch
      mutations studied by NMR spectroscopy.
AB  - Transient complex formation between plastocyanin from Prochlorothrix hollandica
      and cytochrome f from Phormidium laminosum was investigated using nuclear
      magnetic resonance (NMR) spectroscopy. Binding curves derived from NMR titrations
      at 10 mM ionic strength reveal a 1:1 stoichiometry and a binding constant of 6
      (+/-2) x 10(3) M(-1) for complex formation, 1 order of magnitude larger than that
      for the physiological plastocyanin-cytochrome f complex from Ph. laminosum.
      Chemical-shift perturbation mapping indicates that the hydrophobic patch of
      plastocyanin is involved in the complex interface. When the unusual hydrophobic
      patch residues of P. hollandica plastocyanin were reverted to the conserved
      residues found in most other plastocyanins (Y12G/P14L), the binding constant for
      the interaction with cytochrome f was unaffected. However, the chemical shift
      perturbation map was considerably different, and the size of the average
      perturbation decreased by 40%. The complexes of both the wild-type and double
      mutant plastocyanin with cytochrome f were sensitive to ionic strength, contrary
      to the physiological complex. The possible implications of these findings for the
      mechanism of transient complex formation are discussed.

PMID- 12501199
TI  - FTIR detection of water reactions during the flash-induced S-state cycle of the
      photosynthetic water-oxidizing complex.
AB  - Photosynthetic water oxidation is performed via the light-driven S-state cycle in
      the water-oxidizing complex (WOC) of photosystem II (PS II). To understand its
      molecular mechanism, monitoring the reaction of substrate water in each S-state
      transition is essential. We have for the first time detected the reactions of
      water molecules in WOC throughout the S-state cycle by observing the OH
      vibrations of water using flash-induced Fourier transform infrared (FTIR)
      difference spectroscopy. Moderately hydrated (or deuterated) PS II core films
      from Synechococcus elongatus were used to obtain the FTIR difference spectra upon
      the first, second, third, and fourth flash illumination, representing the
      structural changes in the S(1) --> S(2), S(2) --> S(3), S(3) --> S(0), and S(0) -
      > S(1) transitions, respectively. In the weakly H-bonded OH region, bands
      appeared at 3617/3588 cm(-1) as a differential signal in the first-flash spectrum
      and at 3634, 3621, and 3612 cm(-1) with negative intensities in the second-,
      third-, and fourth-flash spectra, respectively. These bands shifted down by
      approximately 940 cm(-1) upon deuteration and by approximately 10 cm(-1) upon
      H(18)O substitution, indicating that they arise from the OH stretches of water
      including the substrate and its intermediates. Strongly D-bonded OD bands of
      water were also identified as broad features in the range of 2600-2200 cm(-1) by
      taking the double difference between the spectra of D(2)(16)O- and D(2)(18)O
      deuterated films. In addition, broad continuum features that probably arise from
      the large proton polarizability of H-bonds were observed around 3000, 2700, 2550,
      and 2600 cm(-1) in the first-, second-, third-, and fourth-flash spectra,
      respectively, of the hydrated PS II film, revealing changes in the H-bond network
      of the protein. The negative OH intensities upon the second to fourth flashes
      might be related to proton release from substrate water. The results presented
      here showed that FTIR detection of water OH(D) bands can be a powerful method for
      investigating the mechanism of photosynthetic water oxidation.

PMID- 12501200
TI  - Identification by MALDI-TOF mass spectrometry of 17 alpha
      bromoacetamidopropylestradiol covalent attachment sites on estrogen receptor
      alpha.
AB  - Mass spectrometry was used to identify the sites of covalent attachment of
      [(14)C]-17alpha-bromoacetamidopropylestradiol ([(14)C]17BAPE(2), an estradiol
      agonist) to the ligand-binding domain (LBD) of mouse estrogen receptor alpha
      (ERalpha). A glutathione S-transferase (GST)-LBD chimera protein was
      overexpressed in Escherichia coli, using a vector encoding GST fused with a C
      terminal portion of mouse ERalpha (Ser(313)-Ile(599)), via a sequence enclosing a
      thrombin cleavage site (located 14 amino acids ahead of Ser313). [(14)C]17BAPE(2)
      covalent labeling experiments were carried out on the GST-LBD chimera immobilized
      on glutathione-Sepharose. After thrombin cleavage of the chimeric LBD, two major
      [(14)C]17BAPE(2)-labeled species of 34 ( approximately 75%) and 30 kDa (
      approximately 25%) were detected by SDS-PAGE and autoradiography. Their identity
      was assessed by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (MALDI-TOF MS): two main signals were consistent with the mass of
      the full-length (Ser(313)-Ile(599)) and truncated LBD (Ser(313)-Ala(573)), both
      comprising the extra 14 N-terminal amino acids and covalently bound
      [(14)C]17BAPE(2) (via HBr elimination). A purified (14)C-labeled LBD preparation
      was trypsinized to identify the covalent attachment sites of 17BAPE(2). HPLC of
      tryptic fragments only revealed two discrete and practically equivalent
      radioactive fractions. MALDI-TOF MS analysis of these two fractions showed only
      two signals which exactly matched the molecular masses of the [(14)C]17BAPE(2)
      alkylated Cys(534)Lys(535) and Cys(421)-Arg(438) peptides, respectively.
      Hydrolysis of the second (14)C-labeled fraction by Staphylococcus aureus V8 Glu-C
      endoproteinase generated signals typical of alkylated the Cys(421)-Glu(423)
      tripeptide. We concluded that Cys421 and Cys534 were equivalent alternative
      covalent attachment sites of 17BAPE(2) on the LBD. These biochemical data were
      interpreted using the crystallographic structures of estradiol-LBD and raloxifene
      or 4-hydroxytamoxifen-LBD complexes. The covalent attachment to Cys421, Cys534,
      or both could be interpreted according to the starting structure. Various
      hypotheses based on the biochemical results and molecular modeling simulations
      are discussed, with the likely involvement of dynamic interconversion between
      multiple conformational states of the LBD-17BAPE(2) complex.

PMID- 12501201
TI  - The catalytic power of ketosteroid isomerase investigated by computer simulation.
AB  - Ketosteroid isomerase (KSI) catalyzes the isomerization of Delta(5)-3
      ketosteroids and Delta(4)-3-ketosteroids at very high rates. Here we examine the
      principles underlying the catalytic efficiency of KSI by computer simulations
      using the empirical valence bond method in combination with molecular dynamics
      free energy perturbation simulations. The simulations reproduce available kinetic
      and structural data very well and allow us to examine several features of the
      catalytic mechanism in detail. It is found that about 60% of the rate enhancement
      is due to stabilization of the negatively charged dienolate intermediate by
      hydrogen bonding. The critical H-bond between Tyr16 and the intermediate is found
      to be a normal ionic H-bond with the preferred proton location on the tyrosine
      residue. The remaining 40% of the catalytic effect originates from a reduction of
      the reorganization energy of the reaction. The possibility of an active site
      water molecule occupying the empty cavity adjacent to the catalytic base (Asp40)
      is also addressed. The existence of such a water molecule could explain how the
      enzyme manages to maintain a low pK(a) for the general base residue.

PMID- 12501202
TI  - Enzyme electrokinetics: hydrogen evolution and oxidation by Allochromatium
      vinosum [NiFe]-hydrogenase.
AB  - The mechanism of catalytic hydrogen evolution and oxidation by Allochromatium
      vinosum [NiFe]-hydrogenase has been studied by protein film voltammetry (PFV)
      with the enzyme adsorbed at a pyrolytic graphite edge electrode. By analyzing the
      entire shapes of catalytic voltammograms, the energetics of the catalytic cycles
      (reduction potentials and acidity constants of the active states), including the
      detailed profiles of activity against pH and the sequences of proton and electron
      transfers, have been determined, and these are discussed with respect to the
      mechanism. PFV, which probes rates as a continuous function of the
      electrochemical potential (i.e., in the "potential domain"), is proven to be an
      invaluable tool for determining the redox properties of an active site in the
      presence of its substrate, at room temperature, and during turnover. This is
      especially relevant in the case of the active states of hydrogenase, since one of
      its substrates (the proton) is always present at significant levels in the
      titration medium at physiological pH values.

PMID- 12501203
TI  - Alterations of the oxygen-evolving apparatus induced by a 305Arg --> 305Ser
      mutation in the CP43 protein of photosystem II from Synechocystis sp. PCC 6803
      under chloride-limiting conditions.
AB  - The psbC gene encodes CP43, a component of Photosystem II (PSII) in higher
      plants, algae, and cyanobacteria. Previous work demonstrated that alteration of
      an arginine residue occurring at position 305 to serine produced a strain (R305S)
      with altered PSII activity (Knoepfle, N., Bricker, T. M., and Putnam-Evans, C.
      (1999) Biochemistry 38, 1582-1588). This strain grew at wild-type rates in
      complete BG-11 media (480 microM chloride) and evolved oxygen at rates that were
      60-70% of the observed wild-type rates. The R305S strain assembled approximately
      70-80% of the functional PSII centers contained in the control strain, and these
      PSII centers were very sensitive to photoinactivation at high light intensities.
      We recently observed that the R305S mutant exhibited a pronounced chloride
      effect. When this mutant was grown in media depleted of chloride (30 microM
      chloride), it exhibited a severely reduced photoautotrophic growth rate. The
      effect of chloride depletion on the growth rate of the mutant was reversed by the
      addition of 480 microM bromide to the chloride-depleted BG-11 media. Oxygen
      evolution rates for the mutant were further depressed to about 22% of that
      observed in control cells under chloride-limiting conditions. Addition of bromide
      restored these rates to those observed under chloride-sufficient conditions. The
      mutant exhibited a significantly lower relative quantum yield for oxygen
      evolution than did the control strain, and this was exacerbated under chloride
      limiting conditions. Fluorescence yield measurements indicated that both the
      mutant and the control strains assembled fewer PSII reaction centers under
      chloride-limiting conditions. The reaction centers assembled by the mutant
      exhibited an enhanced sensitivity to photoinactivation under chloride-limiting
      conditions, with a t(1/2) of photoinactivation of 2.6 min under chloride-limiting
      conditions as compared to a t(1/2) of 4.7 min under normal growth conditions. The
      mutant also exhibited an enhanced stability of its S(2) state and increased
      number of centers in the S(1) state following dark incubation. These results
      indicate that the mutant R305S exhibits a defect in its ability to utilize
      chloride in support of efficient oxygen evolution in PSII. This is the first
      mutant of this type described in the CP43 protein.

PMID- 12501204
TI  - Replacement of tyrosine D with phenylalanine affects the normal proton transfer
      pathways for the reduction of P680+ in oxygen-evolving photosystem II particles
      from Chlamydomonas.
AB  - We have probed the electrostatics of P680(+) reduction in oxygenic photosynthesis
      using histidine-tagged and histidine-tagged Y(D)-less Photosystem II cores. We
      make two main observations: (i) that His-tagged Chlamydomonas cores show kinetics
      which are essentially identical to those of Photosystem II enriched thylakoid
      membranes from spinach; (ii) that the microsecond kinetics, previously shown to
      be proton/hydrogen transfer limited [Schilstra et al. (1998) Biochemistry 37,
      3974-3981], are significantly different in Y(D)-less Chlamydomonas particles when
      compared with both the His-tagged Chlamydomonas particles and the spinach
      membranes. The oscillatory nature of the kinetics in both Chlamydomonas samples
      is normal, indicating that S-state cycling is unaffected by either the histidine
      tagging or the replacement of tyrosine D with phenylalanine. We propose that the
      effects on the proton-coupled electron transfers of P680(+) reduction in the
      absence of Y(D) are likely to be due to pK shifts of residues in a hydrogen
      bonded network of amino acids in the vicinity of Y(Z). Tyrosine D is 35 A from
      Y(Z) and yet has a significant influence on proton-coupled electron transfer
      events in the vicinity of Y(Z). This finding emphasizes the delicacy of the
      proton balance that Photosystem II has to achieve during the water splitting
      process.

PMID- 12501205
TI  - Site-directed mutagenesis of dimethyl sulfoxide reductase from Rhodobacter
      capsulatus: characterization of a Y114 --> F mutant.
AB  - A system for expressing site-directed mutants of the molybdenum enzyme dimethyl
      sulfoxide reductase from Rhodobacter capsulatus in the natural host was
      constructed. This system was used to generate and express dimethyl sulfoxide
      reductase with a Y114F mutation. The Y114F mutant had an increased k(cat) and
      increased K(m) toward both dimethyl sulfoxide and trimethylamine N-oxide compared
      to the native enzyme, and the value of k(cat)/K(m) was lower for both substrates
      in the mutant enzyme. The Y114F mutant, as isolated, was able to oxidize dimethyl
      sulfide with phenazine ethosulfate as the electron acceptor but with a lower
      k(cat) than that of the native enzyme. The pH optimum of dimethyl
      sulfide:acceptor oxidoreductase activity in the Y114F mutant was shown to be
      shifted by +1 pH unit compared to the native enzyme. The Y114F mutant did not
      form a pink complex with dimethyl sulfide, which is characteristic of the native
      enzyme. The mutant enzyme showed a large increase in the K(d) for DMS. Direct
      electrochemistry showed that the Mo(V)/Mo(IV) couple was unaffected by the Y114F
      mutant, but the midpoint potential of the Mo(VI)/Mo(V) couple was raised by about
      50 mV. These data confirm that the Y114 residue plays a critical role in
      oxidation-reduction processes at the molybdenum active site and in oxygen atom
      transfer associated with sulfoxide reduction.

PMID- 12501206
TI  - Mobility of fluorobenzyl alcohols bound to liver alcohol dehydrogenases as
      determined by NMR and X-ray crystallographic studies.
AB  - The relationship between substrate mobility and catalysis was studied with wild
      type and Phe93Ala (F93A) horse liver alcohol dehydrogenase (ADH). Wild-type ADH
      binds 2,3,4,5,6-pentafluorobenzyl alcohol in one position as shown by X-ray
      results, and (19)F NMR shows five resonances for the fluorines of the bound
      alcohol. The two meta-fluorines exchange positions with a rate constant of about
      4 s(-1), indicating that mobility (ring flipping) of the benzyl alcohol is
      relatively restricted. The wild-type enzyme binds 2,3-difluorobenzyl alcohol in
      two alternative conformations that are related by a ring flip and a small
      translation of the fluorinated benzene ring, and the (19)F NMR spectrum shows
      three resonances for the two bound fluorines, consistent with the two
      orientations. Phe-93 interacts with the bound benzyl alcohols, and the F93A
      substitution decreases the rate constants for hydride transfer for benzyl alcohol
      oxidation and benzaldehyde reduction by 7.4- and 130-fold, respectively. The
      structure of F93A ADH crystallized with NAD(+) and 2,3,4,5,6-pentafluorobenzyl
      alcohol is similar to the structure of the wild-type enzyme complex except that
      the pentafluorobenzyl alcohol is not found in one position. The (19)F NMR
      spectrum of the F93A ADH-NAD(+)-pentafluorobenzyl alcohol complex shows three
      resonances for the bound fluorines. Line shape analysis of the spectrum suggests
      the bound pentafluorobenzyl ring undergoes rapid ring-flipping at about 20 000 s(
      1). The F93A substitution greatly increases the mobility of the benzyl alcohol
      but modestly and differentially decreases the probability that the substrate is
      preorganized for hydride transfer.

PMID- 12501207
TI  - Expression and characterization of ferredoxin and flavin adenine dinucleotide
      binding domains of the reductase component of soluble methane monooxygenase from
      Methylococcus capsulatus (Bath).
AB  - Soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath)
      catalyzes the selective oxidation of methane to methanol, the first step in the
      primary catabolic pathway of methanotrophic bacteria. A reductase (MMOR) mediates
      electron transfer from NADH through its FAD and [2Fe-2S] cofactors to the
      dinuclear non-heme iron sites housed in a hydroxylase (MMOH). The structurally
      distinct [2Fe-2S], FAD, and NADH binding domains of MMOR facilitated division of
      the protein into its functional ferredoxin (MMOR-Fd) and FAD/NADH (MMOR-FAD)
      component domains. The 10.9 kDa MMOR-Fd (MMOR residues 1-98) and 27.6 kDa MMOR
      FAD (MMOR residues 99-348) were expressed and purified from recombinant
      Escherichia coli systems. The Fd and FAD domains have absorbance spectral
      features identical to those of the [2Fe-2S] and flavin components, respectively,
      of MMOR. Redox potentials, determined by reductive titrations that included
      indicator dyes, for the [2Fe-2S] and FAD cofactors in the domains are as follows:
      -205.2 +/- 1.3 mV for [2Fe-2S](ox/red), -172.4 +/- 2.0 mV for FAD(ox/sq), and 
      266.4 +/- 3.5 mV for FAD(sq/hq). Kinetic and spectral properties of intermediates
      observed in the reaction of oxidized MMOR-FAD (FAD(ox)) with NADH at 4 degrees C
      were established with stopped-flow UV-visible spectroscopy. Analysis of the
      influence of pH on MMOR-FAD optical spectra, redox potentials, and NADH reaction
      kinetics afforded pK(a) values for the semiquinone (FAD(sq)) and hydroquinone
      (FAD(hq)) MMOR-FAD species and two protonatable groups near the flavin cofactor.
      Electron transfer from MMOR-FAD(hq) to oxidized MMOR-Fd is extremely slow (k =
      1500 M(-1) s(-1) at 25 degrees C, compared to 90 s(-1) at 4 degrees C for
      internal electron transfer between cofactors in MMOR), indicating that cofactor
      proximity is essential for efficient interdomain electron transfer.

PMID- 12501208
TI  - Molecular characterization of NikD, a new flavoenzyme important in the
      biosynthesis of nikkomycin antibiotics.
AB  - Nikkomycin antibiotics are potent inhibitors of chitin synthase, effective as
      therapeutic antifungal agents in humans and easily degradable insecticides in
      agriculture. NikD is a novel flavoprotein that catalyzes the oxidation of
      Delta(1)- or Delta(2)-piperideine-2-carboxylate, a key step in the biosynthesis
      of nikkomycin antibiotics. The resulting dihydropicolinate product may be further
      oxidized by nikD or converted to picolinate in a nonenzymic reaction. Saturated
      nitrogen heterocycles (L-pipecolate, L-proline) and 3,4-dehydro-L-proline act as
      alternate substrates. The ability of nikD to oxidize 3,4-dehydro-L-proline, but
      not 1-cyclohexenoate, suggests that the enzyme is specific for the oxidation of a
      carbon-nitrogen bond. An equivalent reaction is possible with the enamine
      (Delta(2)), but not the imine (Delta(1)), form of the natural piperideine-2
      carboxylate substrate. Apparent steady-state kinetic parameters for the reaction
      of nikD with Delta(1)- or Delta(2)-piperideine-2-carboxylate (k(cat) = 64 min(
      1); K(m) = 5.2 microM) or 3,4-dehydro-L-proline (k(cat) = 18 min(-1); K(m) = 13
      mM) were determined in air-saturated buffer by measuring hydrogen peroxide
      formation in a coupled assay. NikD appears to be a new member of the monomeric
      sarcosine oxidase (MSOX) family of amine oxidizing enzymes. The enzyme contains 1
      mol of flavin adenine dinucleotide (FAD) covalently linked to Cys321. The
      covalent flavin attachment site and two residues that bind substrate carboxylate
      in MSOX are conserved in nikD. NikD, however, exhibits an unusual long-wavelength
      absorption band, attributed to charge-transfer interaction between FAD and an
      ionizable (pK(a) = 7.3) active-site residue. Similar long-wavelength absorption
      bands have been observed for flavoproteins containing an active site cysteine or
      cysteine sulfenic acid. Interestingly, Cys273 in nikD aligns with an active-site
      histidine in MSOX (His269) that is, otherwise, a highly conserved residue within
      the MSOX family.

PMID- 12501209
TI  - Pre-steady-state kinetic studies on the Glu171Gln active site mutant of
      adenosylcobalamin-dependent glutamate mutase.
AB  - Glutamate-171 is involved in recognizing the amino group of the substrate in
      glutamate mutase. The effect of mutating this residue to glutamine on the ability
      of the enzyme to catalyze the homolysis of adenosylcobalamin has been
      investigated using UV-visible stopped-flow spectroscopy. Although Glu171 does not
      contact the coenzyme, the mutation results in the apparent rate constants for
      substrate-induced homolysis of the coenzyme that are slower by 7-fold and 13-fold
      with glutamate and methylaspartate, respectively, than those measured for the
      wild-type enzyme; furthermore, it weakens the binding of these substrates by
      approximately 50-fold and approximately 400-fold, respectively. These
      observations lend support to the idea that the enzyme may use substrate binding
      energy to accelerate homolysis of the coenzyme. The mutation also results in
      isotope effects on coenzyme homolysis that are much smaller than the very large
      effects observed when the wild-type enzyme is reacted with deuterated substrates.
      This observation is consistent with adenosylcobalamin homolysis being slowed
      relative to hydrogen abstraction from the substrate.

PMID- 12501210
TI  - Surface denaturation and amyloid fibril formation of insulin at model lipid-water
      interfaces.
AB  - We consider the effects that different lipid surfaces have upon the denaturation
      and subsequent formation of amyloid fibrils of bovine insulin. The adsorption and
      unfolding kinetics of insulin being adsorbed onto the different lipid surfaces
      under denaturing conditions are studied using FTIR ATR spectroscopy and are
      compared to the bulk solution behavior of the protein. Atomic force microscopy
      studies are also performed to compare the fibrils growing on the different
      surfaces. This study shows that both the adsorption and unfolding kinetics of
      insulin can be described by a sum of exponential processes and that different
      surfaces behave differently, with respect both to one another and to the bulk
      protein solution. The proteins adsorbed onto the surfaces are observed to have
      faster unfolding kinetics than those in the bulk, and the fibril-like structures
      formed at the surfaces are shown to be different in a number of ways from those
      found in bulk solution. The beta-sheet content and growth kinetics of the
      adsorbed proteins also differ from those of the bulk system. An attempt is made
      to describe the observed behavior in terms of simple physical arguments involving
      adsorption, unfolding, and aggregation of the proteins.

PMID- 12501211
TI  - Unusual benefits of macromolecular shielding by polyethylene glycol for reactions
      at the diffusional limit: the case of factor VIIai and tissue factor.
AB  - Protein modification with poly(ethylene glycol) (PEG) can prolong circulatory
      lifetime and lower protein antigenicity in an animal. These benefits may arise
      from the proposed mechanism of PEG action, molecular shielding of the protein
      surface, and lowered interaction with other macromolecules. Proteins that depend
      on macromolecule association for their function would not seem good targets for
      PEG modification as the benefits may be mitigated by loss of function. Indeed,
      high loss of function applied to PEG-modified factor VIIa and to active site
      blocked blood clotting factors Xa or IXa was studied. A surprising finding was
      that PEG-modified, active site-blocked factor VIIa (PEG-VIIai, PEG-40 000)
      retained 40% of its function despite an 18-fold increase in circulatory lifetime.
      The discrepancy between functional loss and increased circulatory lifetime was
      consistent with a process that was limited by the diffusion step of assembly
      rather than the chemical binding step. The impact of PEG-40 000 on diffusion of
      VIIai is small (about 3-fold) relative to its potential impact on molecular
      shielding during the chemical binding step of association. These properties
      extended to a mutant of VIIai (P10Q/K32E, QE-VIIai) that has 25-fold higher
      function than wild-type factor VIIai. Overall, properties of PEG-modified
      proteins can suggest features of the kinetic mechanism and may provide enhanced
      proteins for anticoagulation therapy.

PMID- 12501212
TI  - Induction of helical structure in a heptapeptide with a metal cross-link:
      modification of the Lifson-Roig helix-coil theory to account for covalent cross
      links.
AB  - A short peptide, acetyl-AHAAAHA-carboxamide, has been synthesized and the
      histidines cross-linked with a cis-tetraammineruthenium(III) moiety. In the
      absence of the Ru(III) cross-link, the heptapeptide is essentially structureless,
      as judged by circular dichroism, NMR chemical shift, and NMR-monitored hydrogen
      deuterium exchange data. The presence of the cis-Ru(III) cross-link is confirmed
      by mass spectral data and the characteristic pH dependence of the UV-vis spectrum
      of the cis-(bis-(imidazole))ruthenium(III) unit. Circular dichroism data indicate
      that the Ru(III) cross-linked heptapeptide is approximately 37% helical at 0
      degrees C. The NMR spectrum of the cross-linked peptide has been fully assigned
      using TOCSY and ROESY experiments. ROE interactions and J-coupling data provide
      evidence for helical structure. NMR-monitored hydrogen-deuterium exchange data
      for the Ru(III)-cross-linked peptide, resolved at the level of the individual
      amides, give larger protection factors at the ends than in the center of the
      helix. Steric and polarization effects of the Ru(III) cross-link are proposed to
      cause this unusual apparent protection pattern. A modification to the Lifson-Roig
      helix-coil model to account for the effect of the i,i+4 Ru(III) cross-link on the
      helix-coil transition of a peptide is presented. The model provides an excellent
      fit to the temperature dependence of the circular dichroism spectrum of the
      Ru(III)-cross-linked peptide. The modified model indicates that the effect of the
      cross-link on the nucleation parameter, v(2), is modest (about 7-fold) for
      residues bounded by the cross-link. Significant increases in the propagation
      parameter, w, occur for residues within the cross-link. The modification to the
      Lifson-Roig model accounts for the effect of a Ru(III) cross-link on the circular
      dichroism spectrum of a previously reported 17 residue peptide.

PMID- 12501213
TI  - Interaction of DNA containing Fapy.dA or its C-nucleoside analogues with base
      excision repair enzymes. Implications for mutagenesis and enzyme inhibition.
AB  - Fapy.dA is produced in DNA as a result of oxidative stress. Recently, this lesion
      and its C-nucleoside analogues were incorporated in chemically synthesized
      oligonucleotides at defined sites. The interaction of DNA containing Fapy.dA or
      nonhydrolyzable analogues with Fpg and MutY is described. Fpg efficiently excises
      Fapy.dA (K(m) = 1.2 nM, k(cat) = 0.12 min(-1)) opposite T. The lesion is removed
      as efficiently from duplexes containing Fapy.dA:dA or Fapy.dA:dG base pairs.
      Multiple turnovers are observed for the repair of Fapy.dA mispairs in a short
      period of time, indicating that the enzyme does not remain bound to the product
      duplex. MutY does not incise dA from a duplex containing this nucleotide opposite
      Fapy.dA, nor does it exhibit an increased level of binding compared to DNA
      composed solely of native base pairs. MutY also does not incise Fapy.dA when the
      lesion is opposite dG. These data suggest that Fapy.dA could be deleterious to
      the genome. Fpg strongly binds duplexes containing the beta-C-nucleoside analogue
      of Fapy.dA (beta-C-Fapy.dA) opposite all native nucleotides (K(D) < 27 nM), as
      well as the alpha-C-nucleoside (alpha-C-Fapy.dA) opposite dC (K(D) = 7.1 +/- 1.5
      nM). A duplex containing a beta-C-Fapy.dA:T base pair is an effective inhibitor
      (K(I) = 3.5 +/- 0.3 nM) of repair of Fapy.dA by Fpg, suggesting the C-nucleoside
      may have useful therapeutic properties.

PMID- 12501214
TI  - Site-specific dephosphorylation of endothelial nitric oxide synthase by protein
      phosphatase 2A: evidence for crosstalk between phosphorylation sites.
AB  - The endothelial isoform of nitric oxide synthase (eNOS) is a calcium/calmodulin
      dependent enzyme that catalyzes the synthesis of nitric oxide, a key mediator of
      vascular homeostasis. eNOS undergoes a variety of posttranslational
      modifications, including phosphorylation on at least three residues: serines 116
      and 1179 and threonine 497. Although the agonist-modulated protein kinase
      pathways that lead to eNOS phosphorylation have been studied in detail, the
      signaling pathways governing eNOS dephosphorylation remain less well
      characterized. The present study identifies protein phosphatase 2A (PP2A) as a
      key determinant of eNOS dephosphorylation and enzyme activity. We transfected
      bovine aortic endothelial cells (BAEC) with epitope-tagged cDNAs encoding wild
      type eNOS or a series of phosphorylation-deficient eNOS mutants,
      immunoprecipitated [(32)P(i)] biosynthetically labeled recombinant proteins using
      antibodies directed against the epitope tag and treated the [(32)P(i)]
      phosphorylated eNOS with protein phosphatases. We found that PP2A
      dephosphorylates eNOS residues threonine 497 and serine 1179 but not serine 116
      and that an eNOS mutant lacking these three established phosphorylation sites is
      robustly labeled when expressed in BAEC and is dephosphorylated by PP2A. An
      inhibitor of PP2A increases eNOS enzymatic activity and augments overall levels
      of eNOS phosphorylation, specifically increasing phosphorylation of serines 116
      and 1179. When transfected into BAEC or COS-7 cells, a "phospho-mimetic" eNOS
      mutant in which threonine 497 is changed to aspartate shows attenuated
      phosphorylation at serine 1179 as well as reduced enzyme activity in COS-7 cells.
      Our results indicate that regulation of eNOS dephosphorylation may be a key point
      for control of nitric oxide-dependent signaling pathways in vascular endothelial
      cells.

PMID- 12501215
TI  - Physical and functional interaction between receptor-like protein tyrosine
      phosphatase PCP-2 and beta-catenin.
AB  - We have previously identified a human receptor protein tyrosine phosphatase of
      the MAM domain family, termed PCP-2, in human pancreatic adenocarcinoma cells and
      found that this protein was colocalized with beta-catenin and E-cadherin at cell
      junctions [Wang, H.-Y., et al. (1996) Oncogene 12, 2555-2562]. Its intracellular
      part consists of two tandem phosphatase domains and a relatively large
      juxtamembrane region that is homologous to the conserved intracellular domain of
      cadherins, suggesting a role in the regulation of cell adhesion. This study
      reports that PCP-2 was endogenously expressed at the cell surface and upregulated
      with increased cell density. An in vivo binding assay revealed that PCP-2 could
      directly interact with beta-catenin through a region in the juxtamembrane domain.
      Tyrosine phosphorylation of beta-catenin by EGF or active SrcY527F did not
      disrupt the formation of the PCP-2-beta-catenin complex, while PCP-2 in this
      complex could cause a significant reduction in the phosphorylation level in beta
      catenin. Finally, we showed that PCP-2 was a negative regulator for cell
      migration. In conclusion, interaction of PCP-2 with its substrate beta-catenin is
      involved in the process of cell-cell contact.

PMID- 12501216
TI  - Mutational analysis of synaptobrevin transmembrane domain oligomerization.
AB  - Synaptobrevin 2 is thought to facilitate fusion of synaptic vesicles with the
      presynaptic membrane through formation of a soluble NSF attachment protein
      receptor complex (SNARE) with syntaxin 1a and a synaptosomal associated protein
      of 25 kDa (SNAP-25). Previous reports have described a homodimer of synaptobrevin
      that is dependent on the transmembrane domain. However, these reports disagree
      about the magnitude of dimerization, which makes it difficult to assess the
      biological relevance of this interaction. We used SDS-PAGE and the TOXCAT genetic
      assay to reexamine the homodimerization of the synaptobrevin transmembrane domain
      in detergents and the Escherichia coli inner membrane, respectively. To gauge the
      magnitude of synaptobrevin homodimerization, we used the well-characterized
      glycophorin A homodimer as a positive standard. In contrast to previous studies,
      we found synaptobrevin homodimerization in E. coli is very weak when compared to
      glycophorin A. Recombinant synaptobrevin forms a small amount of dimer and higher
      order oligomers in detergents that are highly dependent on solublization
      conditions. We estimate a dissociation constant of 10 mM for synaptobrevin
      dimerization in detergent. Thus, the dimerization of synaptobrevin in membranes
      is very weak, questioning any possible functional role for this association in
      vivo.

PMID- 12501217
TI  - Dramatic stabilization of the native state of human carbonic anhydrase II by an
      engineered disulfide bond.
AB  - To find a disulfide pair that could stabilize the enzyme human carbonic anhydrase
      II (HCA II), we grafted the disulfide bridge from the related and unusually
      stable carbonic anhydrase form from Neisseria gonorrhoeae (NGCA) into the human
      enzyme. Thus, the two Cys residues at positions 23 and 203 were engineered into a
      pseudo-wild-type form of HCA II (C206S), giving the mutant C206S/A23C/L203C. The
      disulfide bond was not formed spontaneously. The native state of the reduced form
      of the mutant was markedly destabilized (2.9 kcal/mol) compared to that of HCA
      II. Formation of a disulfide bridge was achieved by treatment by oxidized
      glutathione. This led to a significant stabilization of the native conformation.
      Compared to HCA II the unfolding midpoint for the variant was increased from 0.9
      to 1.7 M guanidine HCl, corresponding to a stabilization of 3.7 kcal/mol. This
      makes the human enzyme almost as stable as the model protein NGCA, for which the
      unfolding of the native state has a midpoint at 2.1 M guanidine HCl. The
      stabilized protein underwent, contrary to all other investigated variants of HCA
      II, an apparent two-state unfolding transition, as judged from intrinsic Trp
      fluorescence measurements. A molten-globule intermediate is nevertheless formed
      but is suppressed because of the high denaturant pressure it faces upon rupture
      of the native state.

PMID- 12501218
TI  - Alpha-crystallin regions affected by adenosine 5'-triphosphate identified by
      hydrogen-deuterium exchange.
AB  - ATP interaction with lens alpha-crystallins leading to enhanced chaperone
      activity is not yet well understood. One model for chaperone activity of small
      heat shock proteins proposes that ATP causes small heat shock proteins to release
      substrates, which are then renatured by other larger heat shock proteins. A
      similar role has been proposed for ATP in alpha-crystallin chaperone activity. To
      evaluate this model, ATP-induced structural changes of native human alpha
      crystallin assemblies were determined by hydrogen-deuterium exchange. In these
      experiments, hydrogen-deuterium exchange, measured by mass spectrometry, gave
      direct evidence that ATP decreases the accessibility of amide hydrogens in
      multiple regions of both alphaA and alphaB. The surface encompassed by these
      regions is much larger than would be shielded by a single ATP, implying that
      multiple ATP molecules bind to each subunit and/or ATP causes a more compact
      alpha-crystallin structure. Such a conformational change could release a bound
      substrate. The regions most affected by ATP are near putative substrate binding
      regions of alphaA and alphaB and in the C-terminal extension of alphaB. The
      widespread decrease in hydrogen-deuterium exchange with particularly large
      decreases near substrate binding regions suggests that ATP releases substrates
      via both direct displacement and a global conformational change.

PMID- 12501220
TI  - Tetrahydrobiopterin and dietary restriction in mild phenylketonuria.

PMID- 12501221
TI  - Influenza-related hospitalizations among children in Hong Kong.
AB  - BACKGROUND: It has been difficult to define the burden of influenza in children
      because of confounding by the cocirculation of respiratory syncytial virus (RSV).
      In Hong Kong, China, the influenza and RSV infection seasons sometimes do not
      overlap, thus providing an opportunity to estimate the rate of influenza-related
      hospitalization in a defined population, free from the effects of RSV. METHODS:
      In a retrospective, population-based study, we estimated the influenza-associated
      excess rate of hospitalization among children 15 years old or younger in the Hong
      Kong Special Administrative Region from 1997 to 1999. Data from a single hospital
      with intensive use of virologic analyses for diagnosis were obtained to define
      and adjust for underestimation of the model. RESULTS: Peaks of influenza and RSV
      infection activity were well separated in 1998 and 1999 but overlapped in 1997.
      The adjusted rates of excess hospitalization for acute respiratory disease that
      were attributable to influenza were 278.5 and 288.2 per 10,000 children less than
      1 year of age in 1998 and 1999, respectively; 218.4 and 209.3 per 10,000 children
      1 to less than 2 years of age; 125.6 and 77.3 per 10,000 children 2 to less than
      5 years of age; 57.3 and 20.9 per 10,000 children 5 to less than 10 years of age;
      and 16.4 and 8.1 per 10,000 children 10 to 15 years of age. CONCLUSIONS: In the
      subtropics, influenza is an important cause of hospitalization among children,
      with rates exceeding those reported for temperate regions.

PMID- 12501222
TI  - Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent
      ulcer bleeding in patients with arthritis.
AB  - BACKGROUND: Current guidelines recommend that patients at risk for ulcer disease
      who require treatment for arthritis receive nonsteroidal antiinflammatory drugs
      (NSAIDs) that are selective for cyclooxygenase-2 or the combination of a
      nonselective NSAID with a proton-pump inhibitor. We assessed whether celecoxib
      would be similar to diclofenac plus omeprazole in reducing the risk of recurrent
      ulcer bleeding in patients at high risk for bleeding. METHODS: We studied
      patients who used NSAIDs for arthritis and who presented with ulcer bleeding.
      After their ulcers had healed, we randomly assigned patients who were negative
      for Helicobacter pylori to receive either 200 mg of celecoxib twice daily plus
      daily placebo or 75 mg of diclofenac twice daily plus 20 mg of omeprazole daily
      for six months. The end point was recurrent ulcer bleeding. RESULTS: In the
      intention-to-treat analysis, which included 287 patients (144 receiving celecoxib
      and 143 receiving diclofenac plus omeprazole), recurrent ulcer bleeding occurred
      in 7 patients receiving celecoxib and 9 receiving diclofenac plus omeprazole. The
      probability of recurrent bleeding during the six-month period was 4.9 percent (95
      percent confidence interval, 3.1 to 6.7) for patients who received celecoxib and
      6.4 percent (95 percent confidence interval, 4.3 to 8.4) for patients who
      received diclofenac plus omeprazole (difference, -1.5 percentage points; 95
      percent confidence interval for the difference, -6.8 to 3.8). Renal adverse
      events, including hypertension, peripheral edema, and renal failure, occurred in
      24.3 percent of the patients receiving celecoxib and 30.8 percent of those
      receiving diclofenac plus omeprazole. CONCLUSIONS: Among patients with a recent
      history of ulcer bleeding, treatment with celecoxib was as effective as treatment
      with diclofenac plus omeprazole, with respect to the prevention of recurrent
      bleeding. Renal toxic effects are common in high-risk patients receiving
      celecoxib or diclofenac plus omeprazole.

PMID- 12501223
TI  - Natural history of alkaptonuria.
AB  - BACKGROUND: Alkaptonuria, caused by mutations in the HGO gene and a deficiency of
      homogentisate 1,2-dioxygenase, results in an accumulation of homogentisic acid
      (HGA), ochronosis, and destruction of connective tissue. There is no effective
      therapy for this disorder, although nitisinone inhibits the enzyme that produces
      HGA. We performed a study to delineate the natural history of alkaptonuria.
      METHODS: We evaluated 58 patients with alkaptonuria (age range, 4 to 80 years),
      using clinical, radiographic, biochemical, and molecular methods. A radiographic
      scoring system was devised to assess the severity of spinal and joint damage. Two
      patients were treated with nitisinone for 10 and 9 days, respectively. RESULTS:
      Life-table analyses showed that joint replacement was performed at a mean age of
      55 years and that renal stones developed at 64 years, cardiac-valve involvement
      at 54 years, and coronary-artery calcification at 59 years. Linear regression
      analysis indicated that the radiographic score for the severity of disease began
      increasing after the age of 30 years, with a more rapid increase in men than in
      women. Twenty-three new HGO mutations were identified. In a 51-year-old woman,
      urinary HGA excretion fell from 2.9 to 0.13 g per day after a 10-day course of
      nitisinone (7 days at a dose of 0.7 mg per day and 3 days at 2.8 mg per day). In
      a 59-year-old woman, urinary HGA fell from 6.4 g to 1.7 g per day after nine days
      of treatment with nitisinone (0.7 mg per day). Plasma tyrosine levels in these
      patients rose from approximately 1.1 mg per deciliter (60 micromol per liter) in
      both to approximately 12.8 mg per deciliter (700 micromol per liter) and 23.6 mg
      per deciliter (1300 micromol per liter), respectively, with no clinical signs or
      symptoms. CONCLUSIONS: The reported data on the natural history of alkaptonuria
      provide a basis for the evaluation of long-term therapies. Although nitisinone
      can reduce HGA production in humans with homogentisate 1,2-dioxygenase
      deficiency, the long-term safety and efficacy of this treatment require further
      evaluation.

PMID- 12501224
TI  - Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria.
AB  - BACKGROUND: Hyperphenylalaninemia is a common inherited metabolic disease that is
      due to phenylalanine hydroxylase deficiency, and at least half the affected
      patients have mild clinical phenotypes. Treatment with a low-phenylalanine diet
      represents a substantial psychosocial burden, but alternative treatments have not
      been effective. METHODS: To explore the therapeutic efficacy of
      tetrahydrobiopterin, we performed a combined phenylalanine-tetrahydrobiopterin
      loading test and analyzed the in vivo rates of [13C]phenylalanine oxidation in 38
      children with phenylalanine hydroxylase deficiency (age range, 1 day to 17
      years). We assessed whether responsiveness to tetrahydrobiopterin was associated
      with specific genotypes, and we mapped mutations using a structural model of the
      phenylalanine hydroxylase monomer. RESULTS: In 27 (87 percent) of 31 patients
      with mild hyperphenylalaninemia (10 patients) or mild phenylketonuria (21
      patients), tetrahydrobiopterin significantly lowered blood phenylalanine levels.
      Phenylalanine oxidation was significantly enhanced in 23 of these 31 patients (74
      percent). Conversely, none of the seven patients with classic phenylketonuria had
      a response to tetrahydrobiopterin as defined in this study. Long-term treatment
      with tetrahydrobiopterin in five children increased daily phenylalanine
      tolerance, allowing them to discontinue their restricted diets. Seven mutations
      (P314S, Y417H, V177M, V245A, A300S, E390G, and IVS4-5C-->G) were classified as
      probably associated with responsiveness to tetrahydrobiopterin, and six mutations
      (A403V, F39L, D415N, S310Y, R158Q, and I65T) were classified as potentially
      associated. Four mutations (Y414C, L48S, R261Q, and I65V) were inconsistently
      associated with this phenotype. Mutations connected to tetrahydrobiopterin
      responsiveness were predominantly in the catalytic domain of the protein and were
      not directly involved in cofactor binding. CONCLUSIONS: Tetrahydrobiopterin
      responsiveness is common in patients with mild hyperphenylalaninemia phenotypes.
      Responsiveness cannot consistently be predicted on the basis of genotype,
      particularly in compound heterozygotes.

PMID- 12501225
TI  - Images in clinical medicine. Pulmonary alveolar proteinosis.

PMID- 12501226
TI  - Descriptions of benefits and risks in consent forms for phase 1 oncology trials.
AB  - BACKGROUND: Ethicists have suggested that written consent forms encourage
      participants in phase 1 cancer trials to expect benefit from the experimental
      agent and to overlook serious risks. METHODS: To evaluate the written description
      of direct benefit as well as risk, all consent forms for 1999 phase 1 cancer
      trials were compiled from 80 percent of the National Cancer Institute-designated
      cancer centers and from six of eight large pharmaceutical developers of
      anticancer drugs. In each case, we evaluated the characteristics of the trial,
      the descriptions of the purpose and procedures of the research, the promise of
      benefit, the description of risks, and the description of alternatives. RESULTS:
      Of 272 forms, 268 explicitly mentioned that the trial was research, and 249
      stated that the purpose of the trial was testing for safety. Nearly all forms
      (269) mentioned the right to withdraw from the trial. Almost all forms (260)
      referred to the experimental agent as "treatment" or "therapy." Only one consent
      form promised direct benefit to subjects. Most forms (181) mentioned death as a
      risk, and very few (14) mentioned cure as even a possible benefit. Most (229)
      stated that there was unknown risk involved and indicated that severe or
      permanent harms were possible (224). CONCLUSIONS: Consent forms for phase 1
      oncology studies almost never promise direct benefit to subjects, rarely mention
      cure, and usually communicate the seriousness and unpredictability of risk.
      Although there is room for improvement, the substance of these forms is unlikely
      to be the primary source of misunderstanding by subjects in phase 1 oncology
      trials.

PMID- 12501227
TI  - Hydrophobic surfactant proteins in lung function and disease.

PMID- 12501228
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 40-2002. A 56-year-old man with rapidly worsening dyspnea.

PMID- 12501229
TI  - The global implications of influenza in Hong Kong.

PMID- 12501230
TI  - NSAIDs, Helicobacter pylori, and Pandora's Box.

PMID- 12501231
TI  - Minimally invasive bypass surgery.

PMID- 12501232
TI  - Regression of splenic lymphoma after treatment of hepatitis C virus infection.

PMID- 12501233
TI  - Radical and simple mastectomy.

PMID- 12501234
TI  - Thrombotic microangiopathies.

PMID- 12501235
TI  - Nonfinancial conflicts of interest in research.

PMID- 12501236
TI  - Multidrug resistance in Aspergillus fumigatus.

PMID- 12501237
TI  - Independent external review of health maintenance organizations' medical
      necessity decisions.

PMID- 12501238
TI  - Nucleotide interactions with membrane-bound transporter associated with antigen
      processing proteins.
AB  - The transporter associated with antigen processing (TAP) contains two nucleotide
      binding domains (NBD) in the TAP1 and TAP2 subunits. When expressed as individual
      subunits or domains, TAP1 and TAP2 NBD differ markedly in their nucleotide
      binding properties. We investigated whether the two nucleotide-binding sites of
      TAP1/TAP2 complexes also differed in their nucleotide binding properties. To
      facilitate electrophoretic separation of the subunits when in complex, we used
      TAP complexes in which one of the subunits was expressed as a fluorescent protein
      fusion construct. In binding experiments at 4 degrees C using the photo-cross
      linkable nucleotide analogs 8-azido-[gamma-(32)P]ATP and 8-azido-[alpha
      (32)P]ADP, TAP2 was found to have reduced affinity for nucleotides compared with
      TAP1, when the two proteins were separately expressed. Complex formation with
      TAP1 enhanced the binding affinity of the TAP2 nucleotide-binding site for both
      nucleotides. Binding analyses with mutant TAP complexes that are deficient in
      nucleotide binding at one or both sites provided evidence for the existence of
      two ATP-binding sites with relatively similar affinities in TAP1/TAP2 complexes.
      TAP1/TAP2 NBD interactions appear to contribute at least in part to enhanced
      nucleotide binding at the TAP2 site upon TAP1/TAP2 complex formation. Binding
      analyses with mutant TAP complexes also demonstrate that the extent of TAP1
      labeling is dependent upon the presence of a functional TAP2 nucleotide-binding
      site.

PMID- 12501239
TI  - Copper-stimulated endocytosis and degradation of the human copper transporter,
      hCtr1.
AB  - Copper uptake at the plasma membrane and subsequent delivery to copper-dependent
      enzymes is essential for many cellular processes, including mitochondrial
      oxidative phosphorylation, free radical detoxification, pigmentation,
      neurotransmitter synthesis, and iron metabolism. However, intracellular levels of
      this nutrient must be controlled because it is potentially toxic in excess
      concentrations. The hCtr1 protein functions in high affinity copper uptake at the
      plasma membrane of human cells. In this study, we demonstrate that levels of the
      hCtr1 protein at the plasma membrane of HEK293 cells were reduced when cells were
      exposed to elevated copper. This decrease in surface hCtr1 levels was associated
      with an increased rate of endocytosis, and low micromolar concentrations of
      copper were sufficient to stimulate this process. Inhibitors of clathrin
      dependent endocytosis prevented the trafficking of hCtr1 from the plasma
      membrane, and newly internalized hCtr1 and transferrin were co-localized.
      Significantly, elevated copper concentrations also resulted in the degradation of
      the hCtr1 protein. Our findings suggest that hCtr1-mediated copper uptake into
      mammalian cells is regulated by a post-translational mechanism involving copper
      stimulated endocytosis and degradation of the transporter.

PMID- 12501240
TI  - Inhibition of G-protein-coupled inward rectifying K+ channels by intracellular
      acidosis.
AB  - G-protein-coupled inward rectification K(+) (GIRK) channels play an important
      role in modulation of synaptic transmission and cellular excitability. The GIRK
      channels are regulated by diverse intra- and extracellular signaling molecules.
      Previously, we have shown that GIRK1/GIRK4 channels are activated by
      extracellular protons. The channel activation depends on a histidine residue in
      the M1-H5 linker and may play a role in neurotransmission. Here, we show evidence
      that the heteromeric GIRK1/GIRK4 channels are inhibited by intracellular
      acidification. This inhibition was produced by selective decrease in the channel
      open probability with a modest drop in the single-channel conductance. The
      inhibition does not seem to require G-proteins as it was seen in two G-protein
      coupling-defective GIRK mutants and in excised patches in the absence of
      exogenous G-proteins. Three histidine residues in intracellular domains were
      critical for the inhibition. Individual mutation of His-64, His-228, or His-352
      in GIRK4 abolished or greatly diminished the inhibition in homomeric GIRK4.
      Mutations of any of these histidine residues in GIRK4 or their counterparts in
      GIRK1 were sufficient to eliminate the pH(i) sensitivity of the heteromeric
      GIRK1/GIRK4 channels. Thus, the molecular and biophysical bases for the
      inhibition of GIRK channels by intracellular protons are illustrated. Because of
      the inequality of the pH(i) and pH(o) in most cells and their relatively
      independent controls by cellular versus systemic mechanisms, such pH(i)
      sensitivity may allow these channels to regulate cellular excitability in certain
      physiological and pathophysiological conditions when intracellular acidosis
      occurs.

PMID- 12501241
TI  - Three-dimensional structures of the mammalian multidrug resistance P-glycoprotein
      demonstrate major conformational changes in the transmembrane domains upon
      nucleotide binding.
AB  - P-glycoprotein is an ATP-binding cassette transporter that is associated with
      multidrug resistance and the failure of chemotherapy in human patients. We have
      previously shown, based on two-dimensional projection maps, that P-glycoprotein
      undergoes conformational changes upon binding of nucleotide to the intracellular
      nucleotide binding domains. Here we present the three-dimensional structures of P
      glycoprotein in the presence and absence of nucleotide, at a resolution limit of
      approximately 2 nm, determined by electron crystallography of negatively stained
      crystals. The data reveal a major reorganization of the transmembrane domains
      throughout the entire depth of the membrane upon binding of nucleotide. In the
      absence of nucleotide, the two transmembrane domains form a single barrel 5-6 nm
      in diameter and about 5 nm deep with a central pore that is open to the
      extracellular surface and spans much of the membrane depth. Upon binding
      nucleotide, the transmembrane domains reorganize into three compact domains that
      are each 2-3 nm in diameter and 5-6 nm deep. This reorganization opens the
      central pore along its length in a manner that could allow access of hydrophobic
      drugs (transport substrates) directly from the lipid bilayer to the central pore
      of the transporter.

PMID- 12501242
TI  - The core of the tetrameric mycobacterial porin MspA is an extremely stable beta
      sheet domain.
AB  - MspA is the major porin of Mycobacterium smegmatis mediating the exchange of
      hydrophilic solutes across the cell wall and is the prototype of a new family of
      tetrameric porins with a single central pore of 10 nm in length. Infrared and
      circular dichroism spectroscopy revealed that MspA consists mainly of
      antiparallel beta-strands organized in a coherent domain. Heating to 92 and 112
      degrees C was required to dissociate the MspA tetramer and to unfold the beta
      sheet domain in the monomer, respectively. The stability of the MspA tetramer
      exceeded the remarkable stability of the porins of Gram-negative bacteria for
      every condition tested and was not reduced in the presence of 2% SDS and at any
      pH from 2 to 14. These results indicated that the interactions between the MspA
      subunits are different from those in the porins of Gram-negative bacteria and are
      discussed in the light of a channel-forming beta-barrel as a core structure of
      MspA. Surprisingly, the channel activity of MspA in 2% SDS and 7.6 m urea at 50
      degrees C was reduced 13- and 30-fold, respectively, although the MspA tetramer
      and the beta-sheet domain were stable under those conditions. Channel closure by
      conformational changes of extracellular loops under those conditions is discussed
      to explain these observations. This study presents the first experimental
      evidence that outer membrane proteins not only from Gram-negative bacteria but
      also from mycobacteria are beta-sheet proteins and demonstrates that MspA
      constitutes the most stable transmembrane channel protein known so far. Thus,
      MspA may be of special interest for biotechnological applications.

PMID- 12501243
TI  - The chaperone protein 14-3-3 interacts with 3BP2/SH3BP2 and regulates its adapter
      function.
AB  - Lymphocyte stimulation by immunoreceptors is achieved through the activation of
      multiple signaling pathways leading to cytokine gene transcription. Adapter
      proteins are critical signaling components that can integrate multiple pathways
      by allowing the assembly of multimolecular signaling complexes. We previously
      showed that the cytoplasmic adapter 3BP2 (also known as SH3BP2) promotes NFAT/AP
      1 transcriptional activities in T cells through the activation of Ras- and
      calcineurin-dependent pathways. However, the molecular mechanisms by which
      3BP2/SH3BP2 regulates cell signaling and activation remain poorly documented. In
      this study, using a combination of yeast two-hybrid analysis and biochemical
      approaches, we present evidence for a physical interaction between 3BP2 and the
      chaperone protein 14-3-3. This interaction was direct and constitutively detected
      in yeast and in mammalian cells. Phorbol ester, pervanadate, and
      forskolin/isobutylmethylxanthine stimulations enhanced this interaction, as well
      as co-expression of constitutive active mutants of serine/threonine kinases,
      including protein kinase C. We found that dephosphorylation of 3BP2 by alkaline
      phosphatase disrupted its interaction with 14-3-3 and that 3BP2 was a substrate
      of purified protein kinase C in vitro, suggesting that the phosphorylation of
      3BP2 by upstream kinases was required for 14-3-3 binding. Using deletion mutants
      of 3BP2, two 14-3-3 binding domains were mapped to two proline-rich (residues 201
      240 and 270-310) domains of 3BP2. These domains were shown to contain two 14-3-3
      consensus binding motifs. We identified residues Ser(225) and Ser(277) of 3BP2 as
      being essential for interaction with 14-3-3 family proteins, optimal 3BP2 serine
      phosphorylation, and then for 3BP2-dependent function. Indeed, a 3BP2 mutant
      protein incapable of binding 14-3-3 showed increased capacity to stimulate NFAT
      transcriptional activities, suggesting that 14-3-3 binding to 3BP2 negatively
      regulates 3BP2 adapter function in lymphocytes.

PMID- 12501244
TI  - Localization of the discontinuous immunodominant region recognized by human anti
      thyroperoxidase autoantibodies in autoimmune thyroid diseases.
AB  - The discontinuous immunodominant region (IDR) recognized by autoantibodies
      directed against the thyroperoxidase (TPO) molecule, a major autoantigen in
      autoimmune thyroid diseases, has not yet been completely localized. By using
      peptide phage-displayed technology, we identified three critical motifs, LXPEXD,
      QSYP, and EX(E/D)PPV, within selected mimotopes which interacted with the human
      recombinant anti-TPO autoantibody (aAb) T13, derived from an antibody phage
      displayed library obtained from thyroid-infiltrating TPO-selected B cells of
      Graves' disease patients. Mimotope sequence alignment on the TPO molecule,
      together with the binding analysis of the T13 aAb on TPO mutants expressed by
      Chinese hamster ovary cells, demonstrated that regions 353-363, 377-386, and 713
      720 from the myeloperoxidase-like domain and region 766-775 from the complement
      control protein-like domain are a part of the IDR recognized by the recombinant
      aAb T13. Furthermore, we demonstrated that these regions were involved in the
      binding to TPO of sera containing TPO-specific autoantibodies from patients
      suffering from Hashimoto's and Graves' autoimmune diseases. Identification of the
      IDR could lead to improved diagnosis of thyroid autoimmune diseases by
      engineering "mini-TPO" as a target autoantigen or designing therapeutic peptides
      able to block undesired autoimmune responses.

PMID- 12501245
TI  - Use of a genetically introduced cross-linker to identify interaction sites of
      acidic activators within native transcription factor IID and SAGA.
AB  - An important goal is to identify the direct activation domain (AD)-interacting
      components of the transcriptional machinery within the context of native
      complexes. Toward this end, we first demonstrate that the multisubunit TFIID,
      SAGA, mediator, and Swi/Snf coactivator complexes from transcriptionally
      competent whole-cell yeast extracts were all capable of specifically interacting
      with the prototypic acidic ADs of Gal4 and VP16. We then used hexahistidine tags
      as genetically introduced activation domain-localized cross-linking receptors. In
      combination with immunological reagents against all subunits of TFIID and SAGA,
      we systematically identified the direct AD-interacting subunits within the AD
      TFIID and AD-SAGA coactivator complexes enriched from whole-cell extracts and
      confirmed these results using purified TFIID and partially purified SAGA. Both
      ADs directly cross-linked to TBP and to a subset of TFIID and SAGA subunits that
      carry histone-fold motifs.

PMID- 12501246
TI  - Lipoprotein lipase affects the survival and differentiation of neural cells
      exposed to very low density lipoprotein.
AB  - Lipoprotein lipase (LPL) is a key enzyme involved in the metabolism of
      lipoproteins, providing tissues like adipose tissue or skeletal muscle with fatty
      acids. LPL is also expressed in the brain, fulfilling yet unknown functions.
      Using a neuroblastoma cell line transfected with a NEO- or a LPL-expression
      vector, we have developed a model to study the function of LPL in neurons exposed
      to native or copper-oxidized lipoproteins. The addition to the culture media of
      VLDL with 10 microm copper sulfate led to a significant reduction in the
      viability of NEO transfectants whereas LPL-transfectants were protected from this
      injury. In the presence of VLDL and CuSO(4), LPL transfectants were even able to
      display significant neurite extension. This neuritogenic effect was also observed
      in LPL transfectants exposed to native lipoproteins. However, addition of VLDL
      particles oxidized with CuSO(4) prior to their addition to the culture media
      resulted in neurotoxic effects on LPL transfectants. These findings suggest that
      the presence of LPL in cultured neuronal cells modulates the physiological
      response of neurons following exposure to native or oxidized lipoproteins. LPL
      could thus play a key role in the differentiation of Neuro-2A cells and in the
      pathophysiological effects of oxidative stress in several neurodegenerative
      disorders.

PMID- 12501247
TI  - CDK11 complexes promote pre-mRNA splicing.
AB  - The PITSLRE protein kinases, hereafter referred to as CDK11 because of their
      association with the cyclin L regulatory partner, belong to large molecular
      weight protein complexes that contain RNA polymerase II. These CDK11(p110)
      complexes have been reported to influence transcription as well as interact with
      the general pre-mRNA-splicing factor RNPS1. Some of these complexes may also play
      a role in pre-mRNA splicing. Using a two-hybrid interactive screen, the splicing
      protein 9G8 was identified as an in vivo partner for CDK11(p110). The
      identification of several splicing-related factors as CDK11(p110) interactors
      along with the close relationship between transcription and splicing indicated
      that CDK11(p110) might influence splicing activity directly. Immunodepletion of
      CDK11(p110) from splicing extracts greatly reduced the appearance of spliced
      products using an in vitro assay system. Moreover, the re-addition of these
      CDK11(p110) immune complexes to the CDK11(p110)-immunodepleted splicing reactions
      completely restored splicing activity. Similarly, the addition of purified
      CDK11(p110) amino-terminal domain protein was sufficient to inhibit the splicing
      reaction. Finally, 9G8 is a phosphoprotein in vivo and is a substrate for
      CDK11(p110) phosphorylation in vitro. These data are among the first
      demonstrations showing that a CDK activity is functionally coupled to the
      regulation of pre-mRNA-splicing events and further support the hypothesis that
      CDK11(p110) is in a signaling pathway that may help to coordinate transcription
      and RNA-processing events.

PMID- 12501248
TI  - Molecular basis of H2O2 resistance mediated by Streptococcal Dpr. Demonstration
      of the functional involvement of the putative ferroxidase center by site-directed
      mutagenesis in Streptococcus suis.
AB  - H(2)O(2) is an unavoidable cytotoxic by-product of aerobic life. Dpr, a recently
      discovered member of the Dps protein family, provides a means for catalase
      negative bacteria to tolerate H(2)O(2). Potentially, Dpr could bind free
      intracellular iron and thus inhibit the Fenton chemistry-catalyzed formation of
      toxic hydroxyl radicals (H(2)O(2) + Fe(2+) --> (.)OH + (-)OH + Fe(3+)). We
      explored the in vivo function of Dpr in the catalase- and NADH peroxidase
      negative pig and human pathogen Streptococcus suis. We show that: (i) a Dpr
      allelic exchange knockout mutant was hypersensitive ( approximately 10(6)-fold)
      to H(2)O(2), (ii) Dpr incorporated iron in vivo, (iii) a putative ferroxidase
      center was present in Dpr, (iv) single amino acid substitutions D74A or E78A to
      the putative ferroxidase center abolished the in vivo iron incorporation, and (v)
      the H(2)O(2) hypersensitive phenotype was complemented by wild-type Dpr or by a
      membrane-permeating iron chelator, but not by the site-mutated forms of Dpr.
      These results demonstrate that the putative ferroxidase center of Dpr is
      functionally active in iron incorporation and that the H(2)O(2) resistance is
      mediated by Dpr in vivo by its iron binding activity.

PMID- 12501249
TI  - Bacteriophage T4 Dam DNA-(N6-adenine)-methyltransferase. Processivity and
      orientation to the methylation target.
AB  - We carried out steady state and pre-steady state (burst) kinetic analyses of the
      bacteriophage T4 Dam DNA-(N(6)-adenine)-methyltransferase (MTase)-mediated methyl
      group transfer from S-adenosyl-l-methionine (AdoMet) to Ade in oligonucleotide
      duplexes containing one or two specific GATC sites with different combinations of
      methylated and unmodified targets. We compared the results for ligated 40-mer
      duplexes with those of the mixtures of the two unligated duplexes used to
      generate the 40-mers. The salient results are as follows: (i) T4 Dam MTase
      modifies 40-mer duplexes in a processive fashion. (ii) During processive
      movement, T4 Dam rapidly exchanges product S-adenosyl-l-homocysteine (AdoHcy) for
      substrate AdoMet without dissociating from the DNA duplex. (iii) T4 Dam
      processivity is consistent with an ordered bi-bi mechanism AdoMet downward arrow
      DNA downward arrow DNA(Me) upward arrow AdoHcy upward arrow. However, in contrast
      to the steady state, here DNA(Me) upward arrow signifies departure from a
      methylated site GMTC upward arrow without physically dissociating from the DNA.
      (iv) Following methyl transfer at one site and linear diffusion to a
      hemimethylated site, a reconstituted T4 Dam-AdoMet complex rapidly reorients
      itself to the (productive) unmethylated strand. T4 Dam-AdoHcy cannot reorient at
      an enzymatically created GMTC site. (v) The inhibition potential of fully
      methylated sites 5'-GMTC/5'-GMTC is much lower for a long DNA molecule compared
      with short single-site duplexes.

PMID- 12501250
TI  - Human immunodeficiency virus type-1 Tat/co-activator acetyltransferase
      interactions inhibit p53Lys-320 acetylation and p53-responsive transcription.
AB  - Patients with AIDS are at increased risk for developing various neoplasms,
      including Hodgkin's and non-Hodgkin's lymphomas, Kaposi's sarcomas, and anal
      rectal carcinomas, suggestive that human immunodeficiency virus type-1 infection
      might promote establishment of AIDS-related cancers. Tat, the viral trans
      activator, can be endocytosed by uninfected cells and has been shown to inhibit
      p53 functions, providing a candidate mechanism through which the human
      immunodeficiency virus type-1 might contribute to malignant transformation.
      Because Tat has been shown to interact with histone acetyltransferase domains of
      p300/cAMP-responsive element-binding protein (CREB)-binding protein and p300/CREB
      binding protein-associated factor, we have investigated whether Tat might alter
      p53 acetylation and tumor suppressor-responsive transcription. Here, we
      demonstrate that both Tat and p53 co-localize with p300/CREB-binding protein
      associated factor and p300 in nuclei of IMR-32 human neuroblastoma cells and in
      PC-12 pheochromocytoma cells. Further, p53 trans-activation of the 14-3-3varsigma
      promoter was markedly repressed by Tat-histone acetyltransferase interactions,
      and p53 acetylation by p300/CREB-binding protein-associated factor on residue
      Lys(320) was diminished as a result of Tat-histone acetyltransferase binding in
      vivo and in vitro. Tat also inhibited p53 acetylation by p300 in a dosage
      dependent manner in vitro. Finally, HIV-1-infected Molt-4 cells displayed reduced
      p53 acetylation on lysines 320 and 373 in response to UV irradiation. Our results
      allude to a mechanism whereby the human immunodeficiency virus type-1 trans
      activator might impair tumor suppressor functions in immune/neuronal-derived
      cells, thus favoring the establishment of neoplasia during AIDS.

PMID- 12501251
TI  - Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas.
AB  - Malignant astrocytomas are common human primary brain tumors that result from
      neoplastic transformation of astroglia or their progenitors. Here we show that
      deregulation of the c-Myc pathway in developing astroglia predisposes mice to
      malignant astrocytomas within 2-3 weeks of age. The genetically engineered murine
      (GEM) gliomas harbor a molecular signature resembling that of human primary
      glioblastoma multiforme, including up-regulation of epidermal growth factor
      receptor and Mdm2. The GEM gliomas seem to originate in an abnormal population of
      glial fibrillary acidic protein-expressing cells in the ventricular zone and,
      analogous to human glioblastomas, exhibit molecular and morphological
      heterogeneity. Levels of connexin 43 in the majority of the tumors are unaltered
      from normal tissue, indicating that GEM tumors have retained the capacity to
      establish syncytial networks. In line with this, individual glioma foci are
      composed of a mixture of actively proliferating cells expressing c-Myc and
      proliferating cell nuclear antigen and less dividing bystander cells that express
      glial fibrillary acidic protein and the broad complex tramtrack bric-a
      brac/poxvirus and zinc finger domain protein HOF. A subset of the transgenic mice
      harbored, in addition to brain tumors, vestigial cerebellums in which granule
      cell migration and radial Bergman glial cell differentiation were disturbed.
      These observations argue for a window of vulnerability during astrocyte
      development where c-Myc overexpression is sufficient to trigger the neoplastic
      process, presumably by inducing the sustained growth of early astroglial cells.
      This is in contrast to most other transgenic studies in which c-Myc
      overexpression requires co-operating transgenes for rapid tumor induction.

PMID- 12501252
TI  - Novel role for apolipoprotein E in the central nervous system. Modulation of
      sulfatide content.
AB  - It has long been postulated that apolipoprotein E (apoE) may play a role in lipid
      metabolism in the brain. However, direct evidence that apoE plays such a role is
      lacking. We investigated whether apoE isoforms influence lipid content in the
      brain. We compared the brains of wild-type mice to apoE knockout (-/-) and human
      apoE3 and apoE4 transgenic mice and compared cerebrospinal fluid (CSF) of humans
      with different apoE isoforms. We found that there was no effect of apoE on the
      content of multiple phospholipids, sphingolipids, and cholesterol. There was,
      however, a marked effect of apoE on the sulfatide (ST) content in both the brain
      and CSF. The sulfatide mass in hippocampus and cortex of apoE knockout mice was
      found to be 61 and 114 mol% higher than wild-type mice counterparts at 12 months
      of age. In contrast, the sulfatide content in brain tissues from human apoE4
      expressing mice was approximately 60% less than those found in wild-type mice of
      the same age. The ST mass in human CSF was significantly dependent on the APOE
      genotypes of the subjects. Examination of potential sulfatide carrier(s) in human
      CSF demonstrated that sulfatides are specifically associated with apoE-containing
      high density lipoproteins, suggesting that sulfatide levels in the central
      nervous system (CNS) are likely to be directly modulated by the same metabolic
      pathways that regulate levels of apoE-containing CNS lipoproteins. This novel
      role for apoE in the CNS may provide new insights into the connection of apoE
      with Alzheimer's disease and poor recovery after brain injury.

PMID- 12501253
TI  - Toward understanding the pathogenicity of wild-type measles virus by reverse
      genetics.
AB  - The Edmonston (Ed) strain of measles virus (MV) isolated in primary human kidney
      cells in 1954 has long been thought of as a representative MV strain. But this
      view has been challenged by wild-type MV strains isolated in marmoset B
      lymphoblastoid B95a cells. Although the Ed strain is not pathogenic in monkey
      models, wild-type MV isolated in B95a cells from measles patients induces
      clinical signs typical of human measles, indicating that wild-type MV retains its
      pathogenicity. In addition, wild-type MV has restricted cell tropism and
      replicates only in B95a and some lymphocyte cell lines. This is in sharp contrast
      to the ability of the Ed strain to replicate in a variety of human cell lines. To
      understand the molecular basis for the pathogenicity and the cell tropism of wild
      type MV, we have established a reverse genetics system based on a highly
      pathogenic wild-type MV strain (IC-B) isolated in B95a cells. By using this
      system, we have constructed recombinant wild-type and Ed strains of MV bearing
      heterologous envelope hemagglutinin (H) proteins, and we have examined roles of
      the H protein in determining the cell tropism. Our results clearly indicate that
      the MV cell tropism is determined by not only the H protein, but also other viral
      proteins. We thus propose the presence of another unidentified MV receptor on the
      surface of Vero cells.

PMID- 12501254
TI  - Isolation, part characterization, immunogenicity, and specificity study of
      Plasmodium falciparum culture supernatant.
AB  - A Plasmodium falciparum malaria blood stage antigen was isolated from in vitro
      parasite culture supernatant. The chemical composition of the antigen was studied
      by high-performance thin-layer chromatography, thin-layer chromatography, gas
      liquid chromatography, and other chemical methods. Such analysis indicated it to
      be a glycophospholipid (GPL) and to be composed of xylose, mannose, galactose,
      and glucose linked to a phospholipid, but no inositol. The extracted and purified
      antigen's sensitivity and specificity properties were assessed by laser immuno
      assay and enzyme-linked immunosorbent assay. The results of the sensitivity study
      showed a very high malaria antibody-binding response compared to other known
      antigens. The specificity study of GPL antigen with different nonmalarial samples
      showed no positive response within the limit of significance. This isolated GPL
      antigen appears to be better than other antigens.

PMID- 12501255
TI  - Atypical pathogens in adult patients admitted with community-acquired pneumonia
      in Korea.
AB  - This study examined the prevalence of atypical pathogens causing community
      acquired pneumonia (CAP) in Korea. We collected sera and clinical data for a
      period of 1 year for the adult patients consecutively admitted to Chunchon Sacred
      Heart Hospital with CAP. The diagnosis was made using serologic methods to detect
      antibodies for Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp.,
      Chlamydia psittaci, and Coxiella burnetii. Among 81 recruited patients, C.
      pneumoniae (n = 10, 12.3%) was the leading cause of illness, followed by M.
      pneumoniae (n = 7, 8.6%). One case of C. burnetii pneumonia was detected, but
      there were no cases of Legionella spp. or C. psittaci. Three cases of C.
      pneumoniae pneumonia were co-infected with either M. pneumoniae or C. burnetii.
      There was no significant difference between atypical pneumonia and non-diagnosed
      pneumonia in terms of clinical manifestations. In conclusion, of the atypical
      pathogens causing CAP, C. pneumoniae and M. pneumoniae appear to be the important
      etiologic pathogens in Korea.

PMID- 12501256
TI  - Analysis of malaria endemic areas on the Indochina Peninsula using remote
      sensing.
AB  - We applied remote sensing using satellite images capable of obtaining data over a
      broad range, transcending national borders, as a method of rapidly, precisely,
      and safely increasing our understanding of the potential distribution of malaria.
      Our target region was the so-called Mekong malaria region on the Indochina
      Peninsula. As a malaria index, we used existing distribution maps of total
      reported malaria cases, malaria mortality, vivax malaria and falciparum malaria
      incidences, and so forth for 1997 and 1998. We produced monthly distribution maps
      of a normalized difference vegetation index (NDVI) with values of 0.2+, 0.3+,
      0.35+, and 0.4+ using the geographical information system/remote sensing software
      based on the East Asia monthly NDVI maps of 1997. These maps were overlaid with
      various malaria index distribution maps, and cross-tabulations were carried out.
      The resulting maps with NDVI values of 0.3+ and 0.4+ matched the falciparum
      malaria distribution well, and we realized, in particular, that falciparum
      malaria is prevalent in regions in which NDVI values of 0.4+ continue for 6
      months or more, while cases are fewer in regions with NDVI values of 0.4+ that
      continue for 5 months or less. It will be necessary in the future to examine the
      relationship between NDVI values and the habitats of the various vector
      mosquitoes using high-resolution satellite images and to implement detailed
      forecasts for malaria endemic areas by means of NDVI.

PMID- 12501257
TI  - Absence of association between the Fc gamma receptor IIIA-176F/V polymorphism and
      the severity of malaria in Thai.
AB  - Human Fc gamma receptor (Fc gamma R) genes form a clustered gene family, which
      consists of Fc gamma RIIA, IIB, IIC, IIIA, and IIIB genes, on chromosome 1q23. We
      previously reported that the Fc gamma RIIA-131H/H genotype in combination with
      the Fc gamma RIIIB-NA2 allele is associated with susceptibility to cerebral
      malaria, and that such an association can be caused by linkage disequilibrium
      (LD) between these polymorphisms and the primary associated gene(s) in this
      region. Fc gamma RIIIA is known to exhibit the genetic polymorphism Fc gamma
      RIIIA-176F/V coded for different affinity to IgG1 and IgG3. In this study, we
      examined a possible association between Fc gamma RIIIA-176F/V polymorphism and
      severity of malaria in 462 adult Thai patients with Plasmodium falciparum
      malaria. The frequencies of Fc gamma RIIIA-176V among patients with mild malaria,
      with non-cerebral severe malaria, and with cerebral malaria were 32.7%, 29.9%,
      and 36.3%, respectively. This polymorphism showed neither positive nor negative
      association with the severity of malaria. Thus, we concluded that the association
      of Fc gamma RIIA-131H/R and Fc gamma RIIIB-NA1/NA2 polymorphisms with cerebral
      malaria in Thailand is not due to the LD caused by Fc gamma RIIIA-176F/V.

PMID- 12501258
TI  - Leptospirosis among rice mill workers of Salem, South India.
AB  - Leptospirosis is not commonly reported from the Salem district in central Tamil
      Nadu in India. In October 2000, a rice mill worker, who had fever and jaundice,
      tested positive in leptospiral IgM enzyme-linked immunosorbent assay (ELISA).
      Microbiological and serological investigations were performed on the patient, a
      sample population of the rice mill workers, and the animal and rodent populations
      living in the same premises. Leptospira was isolated from the patient about 2
      weeks after the onset of symptoms when he had recovered from illness following a
      course of doxycycline. The isolate was serovar Icterohaemorrhagiae of serogroup
      Icterohaemorrhagiae. The patient also showed a fourfold rise in titers in
      microscopic agglutination test (MAT) and IgG ELISA. The rice mill workers had a
      seroprevalence rate of 68.3%, which was significantly higher than that among a
      control group consisting of persons engaged in other occupations. Serological
      studies conducted among cattle, dogs, cats, and rats showed seroprevalence rates
      of 52.9%, 50.0%, 66.6%, and 52.1%, respectively. Leptospires were isolated from
      two rats, but the isolates were lost during subculturing and could not be
      characterized. The most predominant serogroup identified by MAT was Autumnalis
      for rice mill workers and all animal populations. The other serogroups that
      reacted in MAT were Icterohaemorrhagiae, Australis, Grippotyphosa, and Patoc.
      Although Australis and Grippotyphosa showed agglutination in the case of human
      samples, none of the animals had detectable titers to these serogroups. The rice
      mills of Salem, having large rodent populations, various animals living in close
      proximity, a wet environment, and unprotected exposure of the workers to the
      environment, constitutes an ideal setting for transmission of leptospirosis and
      could be an epidemiological niche of leptospirosis.

PMID- 12501259
TI  - A case of hemolytic-uremic syndrome associated with shiga toxin 2-producing
      Escherichia coli O121 infection caused by drinking water contaminated with bovine
      feces.

PMID- 12501260
TI  - Salmonella serovar montevideo involved in a food poisoning outbreak at a club for
      elderly persons in April 2002 in Hyogo Prefecture.

PMID- 12501261
TI  - Isolation of a wild type measles virus classified as genotype H1 in osaka city.

PMID- 12501262
TI  - Molecular typing of methicillin-resistant Staphylococcus aureus by protein a gene
      sequencing.

PMID- 12501263
TI  - Exercise improves recovery of ventilation in male asthmatic subjects in the
      steady state.
AB  - The effect of a three-minute exercise step test (submaximal) on the recovery of
      tidal volume (V(T)), respiratory frequency (f(R)) and minute ventilation (V(E))
      has been investigated in non-asthmatic subjects, asthmatic subjects that exercise
      regularly and asthmatics that do not participate in regular exercise. Recovery
      was observed over twenty minutes at two-minute intervals. Ten male non-asthmatic
      subjects (NAS) (mean age 20.7+/- 0.4 yr), six male asthmatic subjects (20.5+/-
      0.5 yr) that exercised regularly (EAS) and six male asthmatic subjects (20.8+/-
      0.5 yr) that did not exercise regularly (NEAS) were studied. Exercise
      significantly increased all the measured variables in all the groups of subjects
      (P<0.001 in each case). At the end of the 20th minute, magnitude of recovery of
      V(T) was 123.3+/- 4.5% in NAS, 102.4+/- 5.1% in EAS (p<0.001) and 87.9+ 5.4% in
      NEAS (p<0.001). Mean rate of recovery of V(T) was highest (6.3%/min) in NAS and
      least in NEAS (4.4%/min). At the end of the (T)observation period, recovery of
      respiratory frequency (f(R)) was 100.0+/- 5.0% in NAS, 100.0+/- 4.5% in EAS and
      89.2+/- 3.0 in NEAS. Mean rate of recovery of f(R) was 5.0%/min in NAS and EAS
      subjects respectively and 4.4%/min in NEAS subjects. Also, at the end of the 20th
      minute, the magnitude of recovery of V(E) was similar between NAS and EAS
      (105.1+/- 1.5% and 101.6+/- 1.75% respectively). Recovery of V(E) was
      significantly less in NEAS (93.9+/- 2.5%; p<0.01). Mean rate of recovery of V(E)
      was similar between NAS and EAS subjects (5.0%/min in each case) and 4.1%/min in
      the NEAS subjects. Thus regular exercise improves the recovery of ventilatory
      parameters in asthmatic subjects.

PMID- 12501264
TI  - Fifteen years analysis of complications following minilaparotomy female
      sterilization in Jos Nigeria.
AB  - A retrospective analysis of complications following female sterilization via
      minilaparotomy performed in Jos University Teaching Hospital between January 1985
      and December 1999 was undertaken to determine the incidence, the type of
      complications and identify ways of improving the service. 2986 clients had female
      surgical contraceptions. Major surgical complications occurred in 0.87% of the
      clients. Minor complications were seen in 4.15% with wound sepsis contributing
      3.75% to the rate. The crude failure rate was 0.23%. Re-anastomosis was the
      reason for the failures not surgical misapplication of devices nor fistulous
      opening as found elsewhere. There was no death in the series. Clients seeking
      surgical contraception should be counseled about the minimal major surgical and
      minor complications that could occur during the procedures. Our center will need
      to focus on infection prevention in female surgical contraception in order for
      the services to enjoy continuous acceptance by the clients.

PMID- 12501265
TI  - Susceptibility profile of Enterococcus faecalis isolated at the Lagos University
      Teaching Hospital, Nigeria.
AB  - Enterococcus faecalis is the most common of the Enterococcus genus causing
      infection, particularly urinary tract infections, worldwide. It is also a common
      cause of nosocomial infections and resistance to various antibiotics is on the
      increase worldwide. Thirty-five strains of E. Faecalis isolated from various
      clinical specimens (blood, wound swabs endocervical swabs but mostly urine) were
      screened for high-level aminoglycoside resistance. Their susceptibility nine
      antibiotics (ampicillin, gentamicin, streptomycin, vancomycin, tetracycline
      cotrimoxazole and chloramphenicol, ciprofloxacin and erthromycin) was also
      determined. All isolates were susceptible to Ampicillin and Vancomycin with MIC90
      of 4microg/ml but resistant to Nalidixic acid with an MIC90>256microg/ml. Four
      (11%) of the isolates showed high-level resistance to Gentamicin while 11(32%)
      exhibited high-level resistance streptomycin after 24 hours incubation. It will
      appear that Ampicillin in combination with gentamicin but not streptomycin, can
      still be used empirically for the treatment of Enterococcal infections.

PMID- 12501266
TI  - Prevalence of serological markers of chronic hepatitis B virus infection in
      diabetics in the Lagos University Teaching Hospital, Lagos.
AB  - Hepatitis B virus (HBV) infection, a major world health problem, is hyper endemic
      in South-East Asia and sub-Saharan Africa including Nigeria. Being a major cause
      of morbidity and mortality, prophylaxis using the highly efficacious hepatitis B
      vaccine is recommended for those at risk. The prevalence of serological markers
      of chronic HBV infection was determined in a population of 100 outpatient
      diabetics and 80 non-diabetic controls at the Medical Outpatient Department of
      the Lagos University Teaching Hospital Idi-Araba between January and July 1992.
      Twenty diabetic patients [20%] and 14 controls [17.5%] had serological markers
      (HbsAg and antiHBc) indicating ongoing chronic HBV infection. The difference
      between diabetics and non-diabetic controls was not statistically significant
      (P>.05). None of the HbsAg and antiHBc positive diabetics [45%] and 8 control
      patients [57%] were HbeAg positive. The presence of serological markers was not
      related to the duration, type of diabetic treatment and degree of diabetic
      control. Our findings suggest that diabetics in Lagos appear not to be more
      predisposed to chronic HBV infection than the rest of the population, and
      therefore would require no special antiHBV prophylaxis.

PMID- 12501267
TI  - Ureaplasma urealyticum as a cause of non-gonococcal urethritis: the Ibadan
      experience.
AB  - Two hundred and eighteen men with confirmed urethritis were investigated for
      Ureaplasma urealyticum at the Special Treatment Clinic, University College
      Hospital, Ibadan between 5th January and 28th December 2000. Sixty-four (29.35%)
      of the 218 patients had gonococcal urethritis whilst 154 (70.65%) had non
      gonococcal urethritis (NGU) out of which 22 (14.3%) had U. urealyticum urethritis
      and 10(6.5%) had Trichomonal urethritis. The difference in the occurrence of U.
      urealyticum between the patients and the control group was highly statistically
      significant (p<0.001). The age range of peak incidence among the patients
      investigated was 20-29 years. There was evidence of urethritis in all the 22 U.
      urealyticum positive cases as shown by the presence of increase in the number of
      polymorphonuclear leucocytes in the specimens collected. A significant difference
      in the nature of the urethral discharge in men with gonorrhoeae compared with U.
      urealyticum positive NGU patients was also demonstrated. Treatment of those
      patients found to be positive for U. urealyticum with a course of oral
      Tetracyline was successful but then the problems posed by the asymptomatic
      Ureaplasma urethritis still remained unanswered.

PMID- 12501268
TI  - Bilateral congenital convex pes valgus   a case report.
AB  - This paper reports bilateral congenital convex pes valgus frequently termed
      vertical talus. A successful simple one-stage surgical reconstruction is
      described to enhance the understanding of the management of this rare complex
      deformity. Long follow up is emphasized because of a high incidence of
      recurrence. There has been a one-year follow up so far. Plantigrade and painless
      feet have been achieved which enables the patient to wear normal shoes.

PMID- 12501269
TI  - Root malformation in mandibular premolars: an endodontic difficulty-report of two
      cases.
AB  - Much of the literature is concerned with variation in root canal morphology
      rather than variation in root morphology. The present communication reports two
      rare cases of patients with aberrant root morphology in all their mandibular
      premolars examined. The role of intra-oral preoperative radiographs of diagnostic
      value is emphasized, without which unexpected complications during endodontic
      treatment or extraction may occur. Failure of endodontic treatment as a result of
      the inability to negotiate and instrument one of the canals in the aberrant root
      is an important difficulty that may be encountered with such variant teeth.

PMID- 12501270
TI  - Failed peritoneal dialysis in a dehydrated nephrotic child, in acute renal
      failure: a case report.
AB  - A case of failed peritoneal dialysis in a 5-year-old male nephrotic who developed
      acute renal failure following severe P. falciparum malaria infection is
      presented. Peritoneal dialysis (PD) failure was sequel to undetected severe
      dehydration which occurred during the diuretic phase of the acute renal failure.
      Pre-dialysis plasma potassium, bicabonate, urea and creatinine concentrations
      were 6.0mmol/L, 13mmol/L, 28mmol/L and 900mmol/L respectively, after about 22
      hours of PD, the plasma K+, HCO-3 Ur and Cr were 5.7mmol/L, 15mmol/L, 32mmol/L
      and 1,090mml/L respectively. The peritoneal dialysate Ur concentration (3.5mmol
      and peritoneal Ur clearance (1.85ml/min/1.73m2) were grossly inadequate. There
      was also, intradialysis hyperglycaemia (12mmol/L owing to massive absorption of
      peritoneal dialysate solution which contains high concentration of glucose.
      Hyperglycaemia was corrected with 0.25 units/kg/dose of soluble insulin
      intravenously, he had two doses. Owing to similarity of clinical and biochemical
      features of dehydration and ARF, all efforts must be made to exclude dehydration
      before embarking on PD in patients with renal failure. Failure to exclude
      dehydration, led to PD failure in this patient.

PMID- 12501271
TI  - A five year appraisal of caesarean section in a northern Nigeria university
      teaching hospital.
AB  - A retrospective analysis of cases of caesarean section performed in Jos
      University Teaching Hospital between January 1994 and December 1998 was
      undertaken to determine the incidence, indications, perinatal and maternal
      outcome. There were 11,571 deliveries with 2083 caesarean sections done giving an
      incidence of 18%. 62.2% of the patients who had caesarean section were booked for
      antenatal care and delivered in the hospital, while 37.8% were unbooked seen as
      emergency. 90% of the operations were done as an emergency while only 10% was
      electively performed. There was a high caesarean section rate in all the age
      groups as well as the various parity distributions. The main indications for the
      elective section were repeat caesarean section, placenta praevia, precious baby,
      severe pregnancy induced hypertension and bad obstetric history while those for
      emergency section were cephalo-pelvic disproportion foetal distress, repeat
      caesarean section, antepartum haemorrhage, severe pregnancy induced
      hypertension/eclampsia, obstructed labour and breech presentation. The maternal
      mortality rate was 624.1/100,000 due mainly to haemorrhage, eclampsia and sepsis
      and there was one anaesthetic death amongst the booked patients. The perinatal
      mortality rate was 81.6/1000. The clinical causes of deaths were birth asphyxia,
      ante-partum haemorrhage, obstructed labour and prematurity.

PMID- 12501272
TI  - The morbidity and mortality of right hemicolectomy for complicated
      intussusception in infants.
AB  - Infants with intussusception in tropical Africa frequently present late.
      Intestinal resection for gangrene or perforation may warrant a right
      hemicolectomy. Over a period of 11 year, 15 (45.5%) of 33 infants with
      intussusception required bowel resection, 10 of which were right hemicolectomies.
      The age range of those who had right hemicolectomy was 3-9 months (median 6
      months) and duration of symptoms 3-8 days (median 6 days). In addition to
      features of intussusception, seven (78%) infants were dehydrated and one was
      anaemic. Six (67%) of 9 infants developed procedure related complications
      postoperatively. Four (44%) had anastomotic dehiscence, associated with abdominal
      wound dehiscence in 2. In 3 of the patients, the anastomosis leaked again
      following repeat resection and anastomosis, necessitating relaparotomy and stoma
      formation. One (11%) patient each had wound infection and prolonged ileus
      respectively. Six (67%) patients died, including the 4 who had anastomotic
      dehiscence. The cause of death was overwhelming infection in 4 patients and
      aspiration of vomitus in two patients. Recommendations are made to minimize
      morbidity and mortality in these infants.

PMID- 12501273
TI  - Collaboration in urological practice in the new millennium.
AB  - The aim of this paper is to highlight areas in which urologists collaborate with
      other healthcare practitioners and to identify further areas of beneficial
      collaboration. A review of the literature using Medline search and the authors 
      clinical experience. There is close collaboration with the radiologists in
      urological investigations and embolization of tumours, aspiration of cysts and
      abscesses as well as obtaining biopsy specimens. Cross referral of patients
      occurs between urologists, gynaecologists, oncologists and radiotherapists.
      Technological advances enabling different specialist to master certain procedures
      like ultrasonography and laser surgery should make collaboration obligatory and
      mandatory. Collaboration also occurs with orthopaedic, paediatric and plastic
      surgeons, proctologists and specialist nurses involved in urological treatments.
      Sometimes, there have been competition and conflicts with the above specialists,
      especially the gynaecologist in the treatment of urogenital fistulae. Close co
      operation among healthcare practitioners will improve the standard of practice to
      the benefit of the patient as well as to promote healthier work atmosphere in
      health care delivery. Conflict and competition are diversionary, costly and
      unnecessary. The urologist appears best placed to lead the way in collaborative
      clinical practice in this millennium.

PMID- 12501274
TI  - Routine use of the gravidogram and foetal growth chart in Benin: is there need to
      customise the gravidogram?
AB  - The Objective of the study is to investigate foetal growth curve amongst the
      women attending the antenatal clinic of the UBTH and determine if the gravidogram
      needs to be customised for use in our community. Five hundred and sixty booked
      antenatal patients with certain last menstrual period dates were recruited for a
      prospective non-randomised longitudinal study. Serial measurement of the
      symphysis-fundus at each antenatal clinic visit was taken using a non-stretch
      tape measure in centimetre. The data collected was analysed for the mean
      longitudinal growth curve, and for the construction of a centile gravidogram
      (10th, 50th, 90th percentile) using a computer programmed ready-to use chart. The
      mothers average height and body mass index was 1.64m +/- 0.06 and 25.9+/-4.24.
      The mean birth weight was 3.13kg +/- 0.49. The male infants were 46.3% of the
      total and were slightly heavier (weight boys vs. girls, 3.15 vs. 3.11kg,
      P=0.467), not fetal growth curve is comparable and draws a parallel with
      international standard gravidogram, except that our babies grow all through
      pregnancy. The foetal growth pattern in Benin is comparable to international
      standard pattern. However, because of infant birth weight and maternal biosocial
      differences there is need to costomise the gravidogram to identify all at risk
      babies in the community.

PMID- 12501275
TI  - Anterior chamber intra-ocular lens surgery at Ago-Iwoye, Ogun State, Nigeria.
AB  - The objective of this paper is to assess the visual outcome and complications
      associated with anterior chamber lens implantation. A retrospective review of all
      patients who had anterior chamber lens insertion at St Mary s Catholic Eye
      Hospital Ago-Iwoye between October 1998 and October 1999 was made. Follow up was
      from two months to one year. 14 eyes of 14 patients had anterior chamber lens
      implantation. The mean age was 62.6 years. Indications for surgery included,
      uncorrected uni-ocular aphakia 28.6%, inadvertent posterior capsule rent 14.2%,
      and uncomplicated extra-capsular surgery 57.1%. 50% of the patients had best
      corrected post-operative acuity of 6/18 or better. Post-operative astigmatism was
      minimal. The observed complications included, vitreous loss (21.4%),
      iridodialysis (7.1%), cornea striae (14.3%), posterior capsule opacity (21.4%),
      uveitis (42.9%) and raised intraovular pressure (14.3%). Anterior chamber lens
      implantation for visual rehabilitation of uni-ocular aphakia is safe and
      effective.

PMID- 12501276
TI  - Factors determining the outcome of management of patients with Burkitt's lymphoma
      at the University College Hospital Ibadan, Nigeria--an eleven year review.
AB  - In recent times, our experience in the chemotherapy of Burkitt's lymphoma
      patients in Ibadan, Nigeria has been that of poor outcome, hence this study was
      undertaken to determine the factors leading to the poor results of chemotherapy
      of Burkitt s lymphoma in Ibadan. A retrospective analysis of Burkitt s Lymphoma
      patients seen over eleven year period, between January 1987 to December 1997 at
      the Paediatrics and Haematology Departments of the University College Hospital,
      Ibadan was carried out. There were 67 patients, mean age 11+5 years (range 4 to
      30 years), 42 males, 25 female giving M:F ratio of 1.7:1. Majority of the
      patients (76.2%) were stage D, only 4.5% were stages A and of the 67 patients,
      only 57 (83.6%) had chemotherapy, 40 of whom had COAP, 8 had COMP and 9 patients
      had either cyclophosphamide or cytosar as monotherapy. Only 22.8% of patients
      that received chemotherapy went into complete remission. In this study, we
      observed a declining overall complete remission rate of 22.8% (compared to 47% in
      1979) in Burkitt s Lymphoma patients. The presence of large amount of fake drugs
      in the Nigerian market may imply that some of the cytotoxic drugs used in these
      patients could have been fake drugs. We suggest that the government should
      subsidize the therapy of these patients as well as eradicate the presence of fake
      drugs in the market, thereby increasing the chances of a cure.

PMID- 12501277
TI  - A comparative evaluation of Cephalosporin C production using various
      immobilization modes.
AB  - The production of Cephalosporin C was investigated in a lab-scale 1.4 l air-lift
      reactor (ALR), using various immobilization modes. Bioparticles were developed by
      forming biofilm of growing hyphae around an inorganic siran particle which
      contained spores of the organism. Silk sachet was the other immobilization
      matrix. The maximum specific growth rate of the Cephalosporium acremonium, free
      cells, pellets, siran carrier and silk sachets were 0.037, 0.003, 0.047, and
      0.035 h(-1), and specific antibiotic productivities (as compared to 100% for free
      cells) were 180, 150, and 125% for siran carrier, silk sachets and pellets,
      respectively. Immobilization modes exhibited enhanced volumetric oxygen transfer
      coefficient and well-controlled, three-phase hydrodynamics.

PMID- 12501278
TI  - Use of 16S rDNA community fingerprints to study cricket hindgut microbial
      communities.
AB  - A nucleic acid-based method was evaluated in the course of a study of microbial
      community structure in the cricket hindgut. Genomic DNA was extracted from the
      hindgut microbial community of Acheta domesticus and used as a template in the
      polymerase chain reaction (PCR) method, using primers that align to well
      conserved regions of the 16S rRNA gene. The rDNA-PCR product was used as a
      community probe to generate restriction fragment length polymorphisms (RFLPs) of
      hindgut bacterial isolates and gut microbial communities of insects fed different
      diets. Fingerprints of the bacterial isolates consisted of several bands
      suggesting multiple rRNA operons. In contrast with soil communities, hindgut
      community RFLP contained distinguishable band patterns. However, community rDNA
      fingerprints were complex and varied among insects fed similar diets, suggesting
      considerable intrinsic variability in the hindgut microbial community structure
      between crickets regardless of dietary regime. These results suggest that
      community RFLP methods using broad-specific phylogenetic probes do not have the
      resolution or specificity required to ascertain the effect of diet on the cricket
      hindgut microbial community structure.

PMID- 12501279
TI  - Screening of heavy metal-tolerant actinomycetes isolated from the Sali River.
AB  - Fifty-three strains of actinomycetes resistant to heavy metals were isolated from
      the Sali River in northwest Argentina. Screening procedures that involve solid
      and liquid synthetic media containing Cd(2+), Cu(2+), or Hg(2+) allowed the
      selection of six strains. These strains showed a quantitative sorption of Cd(2+)
      and Cu(2+) by more than 98% of the initial metal concentrations (0.1, 0.5, and
      1.0 mM) tested.

PMID- 12501280
TI  - Seasonal distribution and characterization of Bacillus thuringiensis isolated
      from sericultural environments in Korea.
AB  - To isolate naturally occurring novel Bacillus thuringiensis strains, we
      investigated the distribution and characteristics of B. thuringiensis from
      samples of sericultural farms in various regions of Korea in the spring and fall.
      Fifty-four B. thuringiensis strains out of 164 samples and 34 B. thuringiensis
      strains out of 135 samples were isolated in the spring and fall, respectively.
      Seventy percent of the isolates in the spring and 15% in the fall were toxic to
      lepidopteran larvae. Dipteran-active isolates were rare (7% in spring and 3% in
      fall isolation). Particularly, B. thuringiensis isolates, which are toxic to both
      Lepidoptera and Diptera, were widely distributed (19% in spring and 62% in fall
      isolation). Non-toxic isolates were also found (4% in spring and 20% in fall
      isolation). B. thuringiensis isolates in the sericultural farms represented 11 H
      serotypes; they were principally B. thuringiensis subsp. aizawai in the spring
      and kurstaki in the fall. B. thuringiensis isolates of serotypes 1, 3a, 3a3b,
      4a4c, 6, 7 and 12 were toxic to Lepidoptera. Seventy isolates produced typical
      rhomboidal inclusions, and the remainder produced parasporal inclusions with
      various morphologies. PCR analysis using cryI gene type-specific primers showed
      that cryIAa and cryIC genes are frequently found in the spring and cryIAa gene is
      a predominant type in the fall. Toxicity, H serotype and the cryI gene contents
      of B. thuringiensis isolated from sericultural farms showed that distribution
      varied depending on the season.

PMID- 12501281
TI  - Lipase activity and gene cloning of Acinetobacter calcoaceticus LP009.
AB  - The production of lipase from Acinetobacter calcoaceticus LP009, a bacterium
      isolated from raw milk, was found to be best induced by Tween-80 at 1.0%
      concentration. It was efficiently secreted, and only a minute amount of activity
      was detected at the cell surface and intracellularly. A. calcoaceticus LP009
      lipase exhibited maximum activity at pH 7.0 and 50 degrees C, and was relatively
      stable upon storage at pH 5.0 to 7.0 and at 4, 30, or 37 degrees C. The enzyme
      was found to be inactivated by EDTA suggesting that it was a metalloenzyme. Its
      activity was reduced by less than 20% with the addition of various ions to
      reaction mixtures, but long storage with them caused approximately 50% reduction
      in subsequent reactions under standard conditions. By contrast, the addition of
      Fe(3+) enhanced activity. The enzyme was highly stable upon storage with 0.1% of
      Triton X-100, Tween-80 or Tween-20, but highly unstable with various organic
      solvents tested. PMSF, a serine enzyme inhibitor, and 2-mercaptoethanol, a
      reducing agent, did not affect enzyme activity. After extraction and transfer,
      the lipase gene was efficiently expressed in recombinant Aeromonas sobria. This
      recombinant strain was shown to have increased hydrolyzing efficiency and have
      high potential for lipid-rich wastewater treatment.

PMID- 12501282
TI  - Screening and identification of a novel lipase from Burkholderia sp. YY62 which
      hydrolyzes t-butyl esters effectively.
AB  - Fatty acid esters composed of sterically hindered alcohol are very poor
      substrates for known lipases. In order to obtain a novel lipase, t-butyl
      octanoate (TBO) was selected as a model substrate to screen for bacteria
      producing lipase(s) which can preferentially hydrolyze bulky esters. Of 279
      strains isolated from 350 soil samples based on the ability to grow with TBO as a
      sole carbon source, one strain (YY62) was chosen for its strong TBO-hydrolyzing
      activity. Strain YY62 is a Gram-negative motile rod and was identified as
      Burkholderia sp. from the taxonomic characters and phylogenetic analysis of 16S
      rDNA nucleotide sequences. Using the activity ratio between TBO and p-nitrophenyl
      acetate as a measure for preference to bulky esters, we confirmed that the lipase
      of strain YY62 was 100-fold superior to commercial lipases in terms of TBO
      hydrolyzing activity.

PMID- 12501283
TI  - Characterization of Leuconostoc species isolated from vacuum-packaged ham.
AB  - Thirty-six isolates of Leuconostoc spp. were isolated from yellow spots that
      occurred on the surface of vacuum-packaged ham. All isolates were Gram-positive,
      catalase-negative cocci that produced gas from glucose and formed more than 90%
      of their lactate as D(-) isomer. These isolates could grow at 4 degrees C but not
      above 30 degrees C and most strains produced yellow spots on the ham. The
      isolates were divided into three groups by sugar fermentation patterns.
      Representative strains from three groups showed intergroup DNA homology values of
      above 88.8%, showing that these groups were composed of a single species. This
      organism was positioned at a separate branch in the genus Leuconostoc on the
      phylogenetic tree based on 16S rRNA sequences, which was assigned to Leuconostoc
      gelidum on the basis of DNA-DNA relatedness.

PMID- 12501284
TI  - Accelerated storage testing of freeze-dried and controlled low-temperature vacuum
      dehydrated Lactobacillus acidophilus.

PMID- 12501285
TI  - In vitro digestion of bacterial and plant fructans and effects on ammonia
      accumulation in cow and sheep rumen fluids.

PMID- 12501286
TI  - Purification of spirosin from Lactobacillus reuteri DSM 20016 and partial
      characterization based on its amino acid sequences.

PMID- 12501287
TI  - Effects of salinomycin and vitamin B(6) on in vitro metabolism of phenylalanine
      and its related compounds by ruminal bacteria, protozoa and their mixture.
AB  - An in vitro study was conducted to examine the effects of salinomycin (SL) and
      vitamin B(6) (B(6)) on the production of phenylalanine (Phe) from phenylpyruvic
      acid (PPY) and phenylacetic acid (PAA) and of PAA from Phe and PPY by mixed rumen
      bacteria (B), mixed rumen protozoa (P) and their mixture (BP). Rumen
      microorganisms were collected from fistulated goats fed lucerne cubes (Medicago
      sativa) and a concentrate mixture (3 : 1) twice a day. Microbial suspensions were
      anaerobically incubated at 39 degrees C for 12 h. Phe and some other related
      compounds in both supernatants and microbial hydrolysates of the incubations were
      analyzed by HPLC. When PPY was used as a substrate, it completely disappeared
      without additives and converted mainly to Phe and PAA on the average by 396 and
      178, 440 and 189, and 439 and 147 &mgr;M in B, P and BP, respectively, during the
      12 h incubation period. The rate of disappearance showed no significant
      differences between the microbial suspensions with and without SL and B(6) during
      the incubation period. The production of Phe from PPY with SL was enhanced
      (p<0.05) by 40, 20 and 19% in B, P and BP, respectively, while PAA production
      from PPY with SL was inhibited (p<0.05) by 35, 37 and 38% in B, P and BP,
      respectively, during the 12 h incubation period. On the other hand, with B(6),
      the production of Phe and PAA from PPY tended to be enhanced by 14 and 17, 9 and
      11, and 7 and 22% in B, P and BP, respectively, during the 12 h incubation
      period. When PAA added as a substrate was incubated in the incubation medium
      without any additives, it disappeared by 483, 462 and 507 &mgr;M and converted
      mainly to Phe on the average by 231, 244 and 248 &mgr;M in B, P and BP,
      respectively. The disappearance of PAA with SL was inhibited (p<0.05) by 16, 15
      and 20%, in B, P and BP, respectively, whereas the disappearance of PAA with B6
      was almost the same as that without B(6) in B and BP suspensions but tended to be
      enhanced by more than 9% in P suspensions during the 12 h incubation period. The
      production of Phe from PAA with SL tended to be inhibited by 12, 11 and 8% in B,
      P and BP, respectively, during the 6 h incubation period, but the inhibition was
      weakened during the 12 h incubation period, whereas Phe production from PAA with
      B(6) tended to be enhanced by 13, 16 and 8% in B, P and BP, respectively. When
      Phe was added as a substrate, the net Phe disappearance without additives was
      549, 365 and 842 &mgr;M and converted mainly to PAA on the average by 254, 205
      and 461 &mgr;M in B, P and BP, respectively. The net disappearance of Phe with SL
      was inhibited (p<0.05) by 38, 28 and 46%, whereas the net disappearance of Phe
      with B(6) was enhanced (p<0.05) by 9, 8 and 7% in B, P and BP, respectively. The
      production of PAA from Phe with SL was inhibited (p<0.05) by 73, 54 and 76% in B,
      P and BP, respectively. On the other hand, with B(6), PAA production from Phe was
      enhanced (p<0.05) by 19, 18 and 20% in B, P and BP, respectively. Based on these
      results, it seems that SL inhibited Phe disappearance and enhanced the synthesis
      of Phe from PPY, though not from PAA, and accumulated free Phe in the medium,
      whereas B(6) also enhanced Phe synthesis both from PPY and PAA, which could
      provide additional amino N for animals.

PMID- 12501288
TI  - Three new species of Kockovaella isolated from plants collected in the Ogasawara
      Islands.
AB  - Five strains of unknown ballistoconidiogenous yeasts, which were isolated from
      plant leaves collected in the Ogasawara Islands, Japan, were taxonomically
      studied. They represent three different species of the genus Kockovaella based on
      morphological, physiological and biochemical characteristics, analysis of small
      subunit ribosomal RNA gene sequences, and DNA-DNA reassociation experiments.
      Three new species, Kockovaella machilophila (1 strain), Kockovaella phaffii (3
      strains) and Kockovaella schimae (1 strain) are proposed for these five strains.

PMID- 12501289
TI  - Production of ubiquinone-10 using bacteria.
AB  - Among the bacterial strains known to contain ubiquinone-10, three strains,
      Agrobacterium tumefaciens KY-3085 (ATCC4452), Paracoccus denitrificans KY-3940
      (ATCC19367) and Rhodobacter sphaeroides KY-4113 (FERM-P4675), were selected as
      excellent producers of this ubiquinone. The ubiquinone-10 production by the
      Agrobacterium and Rhodobacter strains was affected by aeration. An ethionine
      resistant mutant (M-37) derived from A. tumefaciens KY-3085 promoted increased
      production of ubiquinone-10 (20% higher than the parent). Another Agrobacterium
      mutant (AU-55), which was induced by the successive addition of four genetic
      markers, showed a tolerance to the suppression of ubiquinone-10 production caused
      by aeration, and the fermentation time for production was remarkably shortened.
      The amount of ubiquinone-10 produced by this Agrobacterium mutant reached 180
      mg/l in a 58 h culture. A green mutant (carotenoid-deficient mutant, Co-22-11)
      derived from R. sphaeroides KY-4113 produced 350 mg/l of ubiquinone-10 under
      culturing conditions with a limited supply of air, the ubiquinone-10 content
      being 8.7 mg/g-dry cell. In this case, the amount and content corresponded to 2.8
      and 3.6 times larger than those given by the wild-type strain, respectively. A
      multiple-layer structure of cell membrane was observed in the highly ubiquinone
      10 accumulating cell of the green mutant by electron microscopy. The amount of
      ubiquinone-10 produced by P. denitrificans was much lower than those of the other
      two strains.

PMID- 12501290
TI  - Differences among marine and hospital strains of Vibrio cholerae during Peruvian
      epidemic.
AB  - During a period of 18 months of an epidemic of Vibrio cholerae, cultures from 450
      samples of fish, shellfish and seawater were isolated. The highest frequencies of
      occurrence observed were 5.2% in fish from inshore waters, 3.9% in marine snails,
      and 1.8% in mussels and crabs. No incidents were isolated from cultures of fish
      in the open seas or cultures from frozen shrimp. Cultures of marine origin were
      compared with cultures from hospitalized patients, and these revealed marked
      serological and toxigenic differences. Marine strains were mainly non-O1 V.
      cholerae, non toxigenic. We presume fishing off-shore not to be the cause of this
      outbreak. However, marine species from contaminated waters could contain
      toxigenic V. cholerae remaining viable and potentially pathogenic. Methods used
      were more sensitive and specific for detecting marine strains. In this paper the
      need to use more specific methods is discussed.

PMID- 12501291
TI  - Factors influencing bacterial attachment to the ruminal epithelium in vitro.
AB  - Some factors influencing bacterial attachment to the rumen epithelium were
      studied in vitro using mixed rumen bacteria (upper- or lower-layer bacteria
      formed at bacterial sediment by centrifugation), isolated from steers fed a
      roughage diet, and rumen epithelial cells collected from beef cattle given low
      concentrate (50%; LC) and high-concentrate (90%; HC) diets. Optimal incubation
      conditions for bacterial attachment to rumen epithelial cells were 39 degrees C
      for 30 min. The bacteria isolated from the upper layer had a higher attaching
      activity to the LC epithelial cells than those of the lower layer. A higher
      degree of bacterial attachment was observed using the rumen epithelium from
      steers fed the LC diet rather than the HC diet (p<0.01). Ethylenediamine
      dihydroiodide (EDDI) added at 10 through 40 &mgr;g/ml increased bacterial
      attachment to the HC epithelial cells. Ammonia at 50 through 100 &mgr;g/ml
      positively affected bacterial attachment to both LC and HC epithelial cells.
      Bacterial attachment to the HC epithelial cells was enhanced (p<0.01) by the
      addition of a reducing agent (L-cysteine.HCl) but no increase was noted with LC
      cells. L- or D-lactate, volatile and unsaturated fatty acids markedly decreased
      bacterial attachment to rumen epithelial cells.

PMID- 12501292
TI  - Characterization of the antigenic determinant on Fusarium oxysporum recognized by
      a genus-specific monoclonal antibody.
AB  - The antigenic determinant of a monoclonal antibody (MAb) (API9-2) having specific
      reactivity with the fungi grouped into the genus Fusarium was analyzed. The
      culture supernatant of the fungi showed antigenicity against MAb API9-2, proving
      that the antigen exists as an exoantigen. The heat-resistant, proteinase K
      resistant and periodate oxidation-labile features of the antigenic determinant
      indicated its carbohydrate nature. Also, lectin affinity tests and thin-layer
      chromatography analysis suggested that the monosaccharide making up the antigenic
      determinant was mainly mannose. Considering previous reports that the antigen
      exists on the surface of mycelia (by immunofluorescence assay) and is a - 55 kDa
      molecule (by Western blotting analysis), it was concluded that the antigenic
      determinant of MAb API9-2 on F. oxysporum is a mannan component existing on the
      surface of mycelia.

PMID- 12501293
TI  - Production of sound waves by bacterial cells and the response of bacterial cells
      to sound.
AB  - Bacterial cells enhance the proliferation of neighboring cells under stress
      conditions by emitting a physical signal. Continuous single sine sound waves
      produced by a speaker at frequencies of 6-10, 18-22, and 28-38 kHz promoted
      colony formation by Bacillus carboniphilus under non-permissive stress conditions
      of high KCl concentration and high temperature. Furthermore, sound waves emitted
      from cells of Bacillus subtilis at frequencies between 8 and 43 kHz with broad
      peaks at approximately 8.5, 19, 29, and 37 kHz were detected using a sensitive
      microphone system. The similarity between the frequency of the sound produced by
      B. subtilis and the frequencies that induced a response in B. carboniphilus and
      the previously observed growth-promoting effect of B. subtilis cells upon B.
      carboniphilus through iron barriers, suggest that the detected sound waves
      function as a growth-regulatory signal between cells.

PMID- 12501294
TI  - Cloning and nucleotide sequence of carbazole catabolic genes from Pseudomonas
      stutzeri strain OM1, isolated from activated sludge.
AB  - A new carbazole (CAR)-degrading bacterium, called strain OM1, was isolated from
      activated sludge obtained from sewage disposal plants in Fukuoka Prefecture, and
      it was identified as Pseudomonas stutzeri. Anthranilic acid (AN), 2'
      aminobiphenyl-2,3-diol and its meta-cleavage product, 2-hydroxy-6-oxo-6-(2'
      aminophenyl)-hexa-2,4-dienoic acid, were identified as metabolic intermediates of
      CAR in the ethyl acetate extract of the culture broth. Therefore, the CAR
      catabolic pathway to AN in strain OM1 was indicated to be identical to those
      found in the Pseudomonas sp. strains CA06 and CA10. The strain OM1 degraded
      catechol (CAT) via a meta-cleavage pathway in contrast to strains CA06 and CA10,
      which transform catechol into cis, cis-munonic acid. Clones containing a 6.9-kb
      EcoRI fragment and a 3-kb PstI-SphI fragment were isolated from colonies, forming
      a clear zone of CAR and a yellow ring-cleavage product from CAT, respectively.
      Recombinant E. coli carrying the 6.9-kb fragment degraded CAR in the L-broth and
      produced AN. Cell-free extract from the clone carrying a 3-kb PstI-SphI fragment
      had high meta-ring-cleavage dioxygenase activity for CAT. The nucleotide
      sequences of these fragments were determined. The 6.9-kb fragment showed a very
      high degree of homology with the CAR catabolic genes of strain CA10. The amino
      acid and nucleotide sequences of the 3-kb fragment were found to exhibit
      significant homology with the genes for the CAT-catabolic enzymes of TOL plasmid
      pWW0, plasmid NAH7, and plasmid pVI150.

PMID- 12501295
TI  - Transfer of the symbiotic plasmid from Rhizobium leguminosarum biovar trifolii to
      Agrobacterium tumefaciens.
AB  - This study examined the symbiotic properties of Agrobacterium transconjugants
      isolated by transferring a Tn5-mob-marked derivative of the 315 kb megaplasmid
      pRt4Sa from Rhizobium leguminosarum bv. trifolii 4S (wild-type strain) to
      Agrobacterium tumefaciens A136 as the recipient. The genetic characteristics of
      the AT4S transconjugant strains were ascertained by random amplified polymorphic
      DNA (RAPD) analyses and Southern hybridization using Tn5-mob and nod genes as
      probes. Several of these AT4S transconjugants carrying pRt4Sa were able to
      nodulate roots of the normal legume host, white clover. In addition, some AT4S
      transconjugant strains were able to induce nodules on other leguminous plants,
      including alfalfa and hairy vetch. A characteristic bacteroid differentiation was
      observed in clover and alfalfa nodules induced by the AT4S-series strains,
      although nitrogen-fixing activity (acetylene reduction) was not found.
      Furthermore, strain H1R1, obtained by retracing transfer of the pRt4Sa::Tn5-mob
      from strain AT4Sa to strain H1 (pRt4Sa cured derivative of 4S), induced Fix(+)
      nodules on clover roots. These results indicate the evidence that only nod genes
      can be expressed in the Agrobacterium background.

PMID- 12501296
TI  - Isolation and phylogenetic analysis of aerobic copiotrophic ultramicrobacteria
      from urban soil.
AB  - Free-living, aerobic, copiotrophic ultramicrobacteria (UMB) that passed through a
      0.45 &mgr;m membrane filter and had a cell volume of less than 0.3 &mgr;m(3) were
      isolated from polluted urban soil by using both the direct plating method and the
      membrane-filter enrichment technique. The efficiency of recovering UMB from the
      soil was much higher in the latter method than in the former. All of the UMB
      isolates grew well with a doubling time of less than 6 h either in a complex
      nutrient medium or a chemically defined medium. The average cell volumes of the
      UMB isolates, as measured by scanning electron microscopy and epifluorescent
      microscopy with an image analysis, ranged from 0.07 to 0.22 &mgr;m(3). The cell
      size was larger at the exponential phase of growth than at the stationary growth
      stage in general. Ultrathin-section electron microscopy of representatives of the
      UMB isolates showed that they had complete cell wall structures like typical Gram
      negative or -positive bacteria. Phenotypic studies and phylogenetic analyses on
      the basis of 16S rDNA sequences showed that the UMB isolates were classified into
      three major groups, the beta and gamma subdivisions of the Proteobacteria and the
      Actinobacteria (the high G+C DNA group of Gram-positives). However, none of these
      isolates were assigned to any previously known species. These results demonstrate
      that free-living, relatively fast-growing, copiotrophic UMB strains undescribed
      so far are widely distributed in terrestrial environments, including urban soil.

PMID- 12501297
TI  - Transglutaminase in sporulating cells of Bacillus subtilis.
AB  - We screened various Bacillus species producing transglutaminase (TGase), measured
      as labeled putrescine incorporated into N,N-dimethylcasein. As a result, we
      detected TGase activity in sporulating cells of B. subtilis, B. cereus, B. alvei
      and B. aneurinolyticus, and found TGase activity related to sporulation. TGase
      activity of Bacillus subtilis was detected in lysozyme-treated sporulating cells
      during late sporulation, but not in cells without lysozyme treatment or the
      supernatant of the culture broth. TGase was found to be localized on spores.
      TGase was preliminarily purified by gel filtration chromatography for
      characterization. Its activity was eluted in the fractions indicating a molecular
      weight of approximately 23 kDa. TGase could cross-link and polymerize a certain
      protein. The enzyme was strongly suggested to form epsilon-(gamma-glutamyl)lysine
      bonds, which were detected in the spore coat proteins of B. subtilis. The
      activity was Ca(2+)-independent like the TGases derived from Streptoverticillium
      or some plants. It is suggested that TGase is expressed during sporulation and
      plays a role in the assembly of the spore coat proteins of the genus Bacillus.

PMID- 12501298
TI  - Integration of the temperate phage phiU into the putative tRNA gene on the
      chromosome of its host Rhizobium leguminosarum biovar trifolii.
AB  - The plasmid pCI6, carrying the attP site of the temperate phage phiU, integrates
      into the attB site on the chromosome of Rhizobium leguminosarum biovar trifolii
      strain 4S. The 4 kb EcoRI-HindIII region of pCI6 involved in site-specific
      integration was subcloned as the attP fragment of phage phiU and sequenced. The
      attL fragment, one of the new DNA junctions generated from the insertion of pCI6
      into the chromosome of the host Rhizobium, was used as a hybridization probe for
      isolation of the attB fragment of strain 4S. The nucleotide sequence of the 2 kb
      PstI fragment of strain 4S, which hybridized with the attL fragment, was decided
      and compared with that of the attP fragment. A 53 bp common sequence was expected
      to be the core sequence of site-specific integration between phage phiU and
      strain 4S. One of the ORFs on the attP fragment, which was located adjacent to
      the core sequence, had structural homology to the integrase family. However, the
      attB fragment showed high homology with the tRNA genes of Agrobacterium
      tumefaciens and E. coli. A 47 bp sequence of the 53 bp core sequence overlapped
      with this tRNA-like sequence. This indicates that the target site of phage phiU
      integration is the putative tRNA gene on the chromosome of the Rhizobium host.

PMID- 12501299
TI  - Isolation and characterization of a new aromatic compound-degrading alkalitrophic
      bacteria.

PMID- 12501300
TI  - Integration and amplification of the Bacillus sp. 79-23 cellulase gene in the
      Bacillus subtilis 168 chromosome.

PMID- 12501301
TI  - Characterization of copy number mutants of plasmid pSC101.
AB  - We have characterized three copy number mutants of the plasmid pSC101. These
      mutations caused single amino acid substitutions at the 46th, 83rd and 115th
      codons in the rep gene and an increase in the copy number by 4- to 8-fold.
      Although the in vivo and in vitro repressor activities of these mutated Rep
      proteins were quite different from each other, the intracellular concentrations
      of the proteins were maintained at higher levels than the wild-type protein. It
      has been reported that excess amounts of Rep inhibit pSC101 replication (Ingmer
      and Cohen, 1993). This inhibitory activity of Rep was markedly decreased in all
      three mutants. When both the wild-type and one of the mutated rep genes were
      retained in the same plasmids, the copy number of these plasmids was decreased
      compared with plasmids retaining a single mutated rep gene. These results support
      the theory that the inhibitory activity of Rep for its own replication plays an
      important role in copy number regulation.

PMID- 12501302
TI  - Cellular fatty acid profiles of ninety-five strains of Vibrio vulnificus isolated
      from clinical specimens in Korea.
AB  - There have been many reports of primary Vibrio vulnificus septicemia in Korea
      since 1987. This study was undertaken to determine the cellular fatty acid (CFA)
      compositions of 95 clinical strains of V. vulnificus isolated in Korea during
      1985-1995. We compared these results with the CFA profile of V. vulnificus in the
      Microbial Identification System (MIS) (CLIN library version 3.9; Microbial ID
      Inc., Newark, DE, U.S.A.), and the grouping of V. vulnificus by CFA analysis was
      also performed. The relationship between groups and serotypes of V. vulnificus
      was described. Although most of the CFAs in V. vulnificus strains were similar to
      the CFA profile of V. vulnificus in the MIS, some distinctive differences were
      observed between the results of this study and the MIS CFA profile of V.
      vulnificus. First, the means of 2 major CFAs, 16 : 0 and 16 : 1w7c, were 22.16
      and 18.26% in this study but 23.52 and 25.44% in the MIS, respectively. Second,
      all isolates had 11 : 0iso3OH, which was not present in the MIS. Of 95 strains,
      10 strains (10.5%) showed 'NO MATCH' results by the MIS identification. Eighty
      five strains (89.5%) were identified as V. vulnificus by the MIS (the first
      choice identification), but they disclosed low SI values of <0.6 (not 'EXCELLENT
      MATCH') except 2 strains (2.1%). This showed that V. vulnificus strains isolated
      in Korea had different characteristics in CFA composition in comparison with the
      MIS V. vulnificus library. Nine groups comprising all the strains were obtained
      by cluster analysis and were further characterized by principal-component
      analysis. There was heterogeneity between the groups by CFA and serotypes of V.
      vulnificus. The same serovars were distributed into diverse groups.

PMID- 12501303
TI  - Regulation of lactate dehydrogenase synthesis in a ruminal bacterium,
      Streptococcus bovis.
AB  - Lactate dehydrogenase (LDH) was purified from three strains of Streptococcus
      bovis, and the gene ldh was cloned and sequenced. The ldh of S. bovis from a goat
      (TH1) was different from the ldhs of two other strains from cattle (TH2, JB1) in
      that Asp(220) was substituted for Glu. Northern blot analysis revealed that the
      LDH-mRNA of S. bovis was approximately 1.0 kbp, which was transcribed in a
      monocistronic fashion. When cells were grown at pH 6.9 in a batch culture, the
      level of ldh transcript decreased as the growth phase changed; from exponential
      growth to the cessation of growth. The level of ldh transcript was higher in
      cells grown at pH 4.5 than at pH 6.9. This observation was consistent with the
      amounts of LDH in cells and the percentages of lactate produced. These results
      support the hypothesis that S. bovis regulates LDH synthesis at the
      transcriptional level probably in response to intracellular pH.

PMID- 12501304
TI  - Multiple genes for chitin synthase in the zygomycete fungus Phycomyces
      blakesleeanus.
AB  - Two different newly designed primer sets were used in PCR to amplify the
      fragments of chitin synthase (CHS) encoding genes (CHS) from the zygomycete
      fungus Phycomyces blakesleeanus, in which the cell wall is mainly made of chitin
      and chitosan, a deacetylated derivative from chitin. DNA sequencing and alignment
      analysis of the deduced amino acid sequences showed the possible existence of ten
      different genes. Six different DNA fragments, designated PbCHS1, PbCHS2, PbCHS3,
      PbCHS4, PbCHS5 and PbCHS6, homologous to chitin synthase genes were identified in
      250-bp products. From 350-bp products, four different fragments, PbCHS7, PbCHS8,
      PbCHS9 and PbCHS10, were obtained. Clustal analysis suggested that while this
      fungus may not have class III-CHS, class I-, II- and IV-CHS could be present in
      multiple forms. Only PbCHS1, PbCHS2, PbCHS7 and PbCHS8 genes were actively
      expressed in the young germlings cultured in the liquid medium. Transcriptional
      products from PbCHS8 and PbCHS10, 8.2-kb long poly(A)(+)RNA, might suggest the
      existence of an unidentified type of CHS or the possibility of a multifunctional
      gene including CHS function.

PMID- 12501305
TI  - Cloning of a chitinase gene into Bacillus thuringiensis subsp. aizawai for
      enhanced insecticidal activity.
AB  - Chitinase from a high producing strain (TP-1) of Bacillus licheniformis was used
      with B. thuringiensis subsp. aizawai (B.t.a.) in a combined larvicidal assay
      against the pest, Spodoptera exigua. With 10 mU of this chitinase, the LD(50) of
      B.t.a. was reduced by 7.6, 13.8 and 15 times on days 3, 5 and 7, respectively
      when compared to use of B.t.a. alone. In addition, a combination of chitinase (10
      mU) and B.t.a. at a sub-lethal dose retarded growth and development of S. exigua.
      In preparation for transformation of B.t.a., the TP-1 chitinase gene was cloned
      in E. coli DH5alpha and sequenced to reveal a single open reading frame of 1,815
      bp. This open reading frame encoded for a protein of 604 amino acids and a
      characteristic signal peptide sequence of 35 amino acids. The gene was
      subsequently introduced into B.t.a. where it was expressed constitutively. The
      transformed strain showed slightly improved activity against S. exigua when
      compared to the non-transformed strain. This was probably due to the low
      chitinase activity (15 mU/ml) of the transformant, which might be improved by
      further gene manipulation to overexpress enzyme production.

PMID- 12501306
TI  - Erwinia aphidicola, a new species isolated from pea aphid, Acyrthosiphon pisum.
AB  - Five strains of Gram-negative, oxidase-negative, facultatively anaerobic,
      fermentative, motile, rod-shaped bacterium with the general characteristics of
      the family Enterobacteriaceae were isolated from the gut of multiple specimens of
      the pea aphid. All the strains caused aphid mortality when ingested by insects
      via a synthetic diet. The results of biochemical tests showed that these strains
      are most related to Erwinia herbicola and Pantoea agglomerans. According to DNA
      DNA hybridization, the five strains showed more than 96% relatedness to each
      other, indicating that these organisms are members of a single species. These
      strains were most closely related to Erwinia herbicola (22% DNA relatedness).
      Phenotypic differentiation of these strains from Erwinia herbicola, which was
      also detected from aphid gut, was based on negative reactions in tests of yellow
      pigment production, gelatin liquefaction, acid production from inulin, starch and
      dulcitol, and positive acid production from melibiose, inositol, cellobiose and
      glycerol. On the basis of these data, the name Erwinia aphidicola is proposed for
      the new organism. The type strain is strain X 001 (=IAM 14479).

PMID- 12501307
TI  - Phylogenetical relationship based on groE genes among phenotypically related
      Enterobacter, Pantoea, Klebsiella, Serratia and Erwinia species.
AB  - In an attempt to define the phylogenetical relationship among 17 phenotypically
      related species of genera Enterobacter, Pantoea, Serratia, Klebsiella and
      Erwinia, we determined almost all of their groE operon sequences using the
      polymerase chain reaction direct sequencing method. The number of nucleotide
      substitutions per site was 0.12+/-0.030. The value was 3.6-fold higher than that
      of 16S rDNA. As a result, we were successful in constructing molecular
      phylogenetic trees which had a finer resolution than that based on the 16S rDNA
      sequences. The phylogenetic trees based on the nucleotide sequences and deduced
      amino acid sequences of groE operons indicated that the members of genera
      Enterobacter, Pantoea and Klebsiella were closely related to each other, while
      Serratia and Erwinia species except Erwinia carotovora, made distinct clades. The
      close relationship between Enterobacter aerogenes and Klebsiella pneumoniae, that
      had been suggested by biochemical tests and DNA hybridization, was also supported
      by our molecular phylogenetic trees.

PMID- 12501308
TI  - Probiotic effect of Lactobacillus sp. DS-12 in flounder (Paralichthys olivaceus).
AB  - Pea aphids were reared aseptically in the laboratory and fed on strains of
      Erwinia aphidicola, Erwinia herbicola, Klebsiella pneumoniae, Escherichia coli
      and bacterium W, an aphid enterobacterium, by mixing with a synthetic diet to
      determine whether these bacteria have pathogenicity to the insect. It turned out
      that Er. aphidicola and Er. herbicola grew in aphid gut, while K. pneumoniae, Es.
      coli and bacterium W were effectively eliminated. In the case of Er. aphidicola,
      ingestion of a single dose of 10(3) CFU/ml was enough to infect aphid gut and to
      prevent post-final ecdysis growth of the insect. As a result, the body weight of
      the infected aphids was significantly reduced (p<0.01). A concentration of 10(5)
      CFU/ml of Er. aphidicola caused aphid mortality. In contrast, Er. herbicola
      demanded 10(5) CFU/ml to colonize in aphid gut, and seemed to have no effect on
      insect health.

PMID- 12501309
TI  - Effect of heavy metals on chromate reduction by Bacillus subtilis.

PMID- 12501310
TI  - Phylogenetic relationships of activated sludge isolates of ammonia oxidizers with
      different sensitivities to ammonium sulfate.

PMID- 12501311
TI  - Isolation and characterization of anaerobic indole- and skatole-degrading
      bacteria from composting animal wastes.
AB  - Four species of indole-degrading Clostridium and 3 species of skatole-degrading
      Clostridium were isolated from piggery or chicken manure composting processes.
      Since type strains of respective isolates did not degrade these compounds, the
      degradability of the compounds was a novel characteristic. All isolates were
      mesophilic. The maximum growth allowance concentrations of these isolates were
      300 to 800 mg/l in indole and 100 to 300 mg/l in skatole. All isolates showed
      better growth and utilization of indolic compounds in nutrient-rich medium than
      in minimal medium. Skatole-degrading isolates degraded some substituted indoles
      tested, 3-indoleacetic acid, indole and oxindole, but did not degrade 1
      methylindole, 2-methylindole, isatin or anthranilic acid. On the other hand,
      indole-degrading isolates degraded only oxindole. The growth of Clostridium
      malenominatum A-3 was inhibited by a low concentration (0.005%) of indole or
      skatole, even when 200-fold excess glucose was present in the medium. When 0.03%
      indole or skatole was added to the medium, C. malenominatum A-3 showed a lag
      phase for about 10 and 70 h, respectively. When 0.01% of these compounds was
      added to the medium, the uptake of glucose was inhibited. C. malenominatum A-3
      degraded these compounds under nutrient-rich and minimal conditions.

PMID- 12501312
TI  - Growth phase-dependent transcription of emrKY, a homolog of multidrug efflux
      emrAB genes of Escherichia coli, is induced by tetracycline.
AB  - The genes emrK and emrY were found between genes dsdA and evgA at 51 min on the
      Escherichia coli chromosome and form an operon. EmrK and EmrY are 50.4 and 63.3%
      identical in amino acid sequences to EmrA and EmrB, respectively, which together
      make up a multidrug resistant pump. To show that the emrKY operon can be
      expressed, we cloned the promoter with pMC1403 and constructed an emrK-lacZ'
      protein fusion plasmid, pMKD1. In E. coli MC4100 containing pMKD1, its expression
      was increased in the presence of a subinhibitory concentration of tetracycline,
      chloramphenicol or salicylate, but not by carbonylcyanide m
      chlorophenylhydrazone, nalidixic acid or kanamycin. Furthermore, we have shown
      that emrKY transcription dependent on the growth phase is actually induced by
      tetracycline using a S1 nuclease protection assay.

PMID- 12501313
TI  - Ascomycetous yeasts from tropical intertidal dark mud of southeast Brazilian
      estuaries.
AB  - Four different intertidal estuarine sediments had distinct yeast communities. One
      hundred-ninety-three yeast isolates were classified in 47 species, with 34 of
      these in the genus Candida. Candida tropicalis was the only ascomycetous species
      isolated from all four sites. Other opportunistic pathogens including Candida
      glabrata, Candida guilliermondii, Candida parapsilosis and Candida krusei were
      present, especially at the more polluted sites. Pichia species were also frequent
      isolates with Pichia membranaefaciens, and its anamorph, Candida valida, and
      other phenotypically similar low assimilation profile species the most frequent.
      Kluyveromyces aestuarii was prevalent at the only site with well established
      mangrove vegetation, but not present at the other sites. The sediment yeast
      communities were distinct from each other, but more similar to each other than to
      the yeast communities of other ecosystems in the same geographic region.

PMID- 12501314
TI  - The ectomycorrhizal basidiomycete Hebeloma circinans harbors a linear plasmid
      encoding a DNA- and RNA polymerase.
AB  - Bulk DNA isolated from the ectomycorrhizal basidiomycete Hebeloma circinans was
      treated with proteinase K and submitted to agarose gel electrophoresis. In
      addition to high molecular weight genomic DNA, three minor bands were detected.
      The band with the highest electrophoretic mobility (2.2 kbp) corresponds to
      double-stranded RNA. The two other bands, termed pHC1 and pHC2, were shown to be
      dsDNA molecules of 10.3 and 9.1 kbp, respectively. Treatment of the pHC elements
      with 3'- and 5'-specific exonucleases revealed a linear structure and proved that
      the 5' ends are protected from digestion; for pHC2, linearity was confirmed by
      restriction mapping. A 3.2 kbp HindIII fragment of pHC2 was cloned and sequenced;
      it contains two open reading frames encoding putative viral B type DNA and RNA
      polymerases. Thus, the fungus harbors a typical linear plasmid, up to now, rarely
      described for basidiomycetes and hitherto unknown for mycorrhizal species.

PMID- 12501315
TI  - Interactive effects of UV-B and Cu on photosynthesis, uptake and metabolism of
      nutrients in a green alga Chlorella vulgaris under simulated ozone column.
AB  - This study demonstrated a general reduction in photosynthesis (carbon fixation,
      O(2)-evolution and photochemical electron transport chain), the uptake of
      NH(4)(+), NO(3)(-), urea and PO(4)(3+), and activities of nitrate reductase,
      urease, acid phosphatase and ATPase following UV-B and copper exposure of
      Chlorella vulgaris in the absence or presence of 1 and 2 ppm concentrations of a
      4-inch-thick ozone layer. Though the effect of stressors used in combination was
      very detrimental to the above processes, selected concentrations of ozone not
      only counteracted the UV-B-induced inhibition of the above processes, but also
      stimulated O(2)-evolution and the photochemical electron transport chain.
      Kinetics of nutrient uptake and enzyme activities demonstrated that UV-B causes
      structural change(s) in the enzymes/carriers responsible for the uptake of
      NH(4)(+), NO(3)(-), urea and PO(4)(3+) as well as their assimilatory enzymes.
      Except for nitrate reductase, copper was found to compete for the binding sites
      of all the above enzymes. Synergistic inhibition of photosynthetic activity,
      nutrient (except NH(4)(+)) uptake, and enzyme activities by UV-B+Cu seems to be
      due to increased Cu uptake as a consequence of altered membrane permeability
      brought about by the peroxidation of membrane lipids in UV-B-exposed cells.

PMID- 12501316
TI  - Development of a new chemically defined sporulation medium for the yeasts in the
      genus Lipomyces.
AB  - A chemically defined sporulation medium (AF medium) for the yeasts belonging to
      the genus Lipomyces was developed. The chemical composition was derived from
      chemical analyses of soybean extract. Some chemical modification of the AF medium
      indicated that the nitrogen sources (aspartic and glutamic acids) and zinc ion
      were essential for sporulation. The significance of medium pH was discussed.

PMID- 12501317
TI  - Phylogenetic characterization of a new thermoacidophilic bacterium isolated from
      hot springs in Japan.
AB  - Three strains of thermophilic-acidophilic bacteria isolated previously from
      different hot springs in Japan were characterized by molecular genetic methods.
      The strategy taken involved PCR amplification, sequencing and restriction pattern
      analysis of 16S rDNA, 16S-23S rDNA spacer polymorphism analysis and genomic DNA
      DNA hybridization. A phylogenetic analysis based on 16S rDNA sequences showed
      that the new thermoacidophilic isolates formed a genetically coherent group at
      the species level and fell into a major cluster together with members of the
      genera Alicyclobacillus and Sulfobacillus with A. acidocaldarius and A.
      acidoterrestris as their closest relatives. The levels of binary sequence
      similarity between the isolates and the two Alicyclobacillus species were 97.6 to
      97.9%, values considered low enough to warrant placement of the isolates in a
      distinct species of the genus Alicyclobacillus. The 16S rDNA restriction pattern
      analysis, but not 16S-23S rDNA spacer polymorphism analysis, was useful for
      differentiating the isolates from the established Alicyclobacillus species. DNA
      DNA hybridization assays demonstrated a distinct phylogenetic position of our
      isolates as a genospecies within the genus Alicyclobacillus. On the basis of
      these results, the thermoacidophilic isolates should be classified into a new
      species of Alicyclobacillus. The results of this study suggest that this new
      genospecies of Alicyclobacillus is widely distributed in hot springs in Japan.

PMID- 12501318
TI  - Probiotic effect of Lactobacillus sp. DS-12 in flounder (Paralichthys olivaceus).

PMID- 12501319
TI  - DNA bending of pSC101 ori induced by Rep, a replication initiator protein and
      IHF.
AB  - Purified Rep (or RepA) protein, a replication initiator of plasmid pSC101, is
      present almost solely in the dimer form, and its binding activity for the
      directly repeated sequences (iterons) in the replication origin (ori) is very
      low. When Rep protein was treated with guanidine hydrochloride followed by
      renaturation, it was shown to bind to the iterons with very high efficiency. A
      gel shift experiment suggested that guanidine-treated Rep bound to iterons as a
      monomer form. The Rep monomer bound noncooperatively to the three iterons and
      induced bending of the DNA helix axis in the same direction (about 100 degrees ).
      The configuration of the IHF box that is a binding site of another DNA bending
      protein IHF, the three iterons and an AT-rich region between these sequences was
      important for efficient bending of the ori region. Furthermore, a mutant Rep
      protein (Rep(IHF)) which can support the plasmid replication in IHF-deficient
      host cells was purified, and it was found that affinity of the Rep(IHF) monomer
      for iterons was similar to that of wild-type Rep and bent DNA only 14 degrees
      more strongly than did the wild-type Rep. Rep(IHF)-dependent plasmid replication,
      however, required both enhancer regions, par and IR-1, in addition to "core ori"
      as a minimal essential ori, whereas only one of these two enhancers was necessary
      for wild-type Rep-dependent replication. How Rep(IHF) can support plasmid
      replication in the absence of IHF is discussed.

PMID- 12501320
TI  - Ability of high hydrostatic pressure treated plasmids and cells of Escherichia
      coli to genetically transform.
AB  - The exposure of plasmid pUC18 and pBR322 DNA to high hydrostatic pressure
      increased the ability of plasmids to transform competent Escherichia coli cells.
      For pUC18 plasmid, a pressure of 400 MPa, and for pBR322, a pressure of 200 MPa
      was found to provide the highest transformation efficiency. The DNA duplexes of
      the two plasmids were found to be the most stable for melting conditions at these
      pressures. At pressures higher than these, both the stability of the duplex DNA
      and the transformation efficiency were affected. The stabilizing effect of high
      hydrostatic pressure on the hydrogen bond may be responsible for the observed
      increase in transformation efficiency of the pressure-exposed plasmid DNA. The
      possibility of pressure-induced changes in the structure and conformation of DNA
      was studied using various techniques. In agarose gel electrophoresis, pressure
      treated plasmids (pUC18 at 400 MPa and pBR322 at 200 MPa) consistently showed
      visibly distinct higher mobility compared to untreated plasmids. Pressure-treated
      pUC18 as well as pBR322 DNA showed significant reduction in ethidium bromide
      binding as is evident from the reduced intensity of fluorescence of the dye bound
      pressure-treated DNA. Spectroscopic studies using circular dichroism and Fourier
      transform infrared (FTIR) spectroscopy also showed significant differences in the
      absorption profiles of pressure-treated plasmids as compared to an untreated
      control. These studies revealed that the pressure-induced changes in the
      conformation of these DNAs may be responsible for the observed increase in the
      transformation ability of the plasmids. On the other hand, the exposure of
      competent cells of E. coli to a high hydrostatic pressure of 50 MPa not only
      reduced their colony-forming ability but also drastically reduced their ability
      to take up plasmid DNA.

PMID- 12501321
TI  - Characterization of multicopy suppressor genes that complement a defect in the
      Wis1-Sty1 MAP kinase cascade involved in stress responses in Schizosaccharomyces
      pombe.
AB  - The Wis1-Sty1 mitogen-activated protein (MAP) kinase cascade is one of the major
      signaling systems involved in a wide range of stress responses in
      Schizosaccharomyces pombe. It is known that Deltawis1 and Deltasty1 mutants
      exhibit highly pleiotropic phenotypes, including a phenotype of temperature
      sensitivity for growth. In this study, we screened multicopy suppressor genes
      that allow both the Deltawis1 and Deltasty1 mutants to grow simultaneously at a
      non-permissive temperature, 37 degrees C. Two such multicopy suppressors were
      cloned and characterized as sds23(+) and hxk2(+) genes. The former is known to
      specify a protein that functions as a multicopy suppressor for mutations of the
      PP1 protein phosphatase and the 20S cyclosome/anaphase-promoting complex (APC),
      and the latter encodes hexokinase 2. It was revealed that the multicopy sds231
      gene restored a defect in the mating efficiency caused by the Deltawis1 and
      Deltasty1 mutations, whereas the multicopy hxk2(+) gene suppressed a phenotype of
      heat-shock sensitivity for growth of these mutant cells. These findings are
      discussed with special reference to the Wis1-Sty1 MAP kinase signaling pathway in
      S. pombe.

PMID- 12501322
TI  - Isolation and characterization of Saccharomyces cerevisiae genes differentially
      expressed under different growth conditions.
AB  - The budding yeast Saccharomyces cerevisiae, like many other microorganisms,
      responds to nutrient starvation by arresting growth and entering into a non
      proliferating stationary phase. Studies on the response of S. cerevisiae cells to
      growth arrest might provide further insight into the non-proliferative states of
      cells in multi-cellular eukaryotic organisms. Changes might occur at the
      transcription, translation, and post-translational levels in cells upon entry
      into the stationary phase. To search for the genes differentially expressed in
      yeast cells during different growth phases, we have performed systematic Northern
      hybridization experiments using probes prepared for a large number of genes/ORFs.
      We have thus isolated and characterized 42 cDNA clones containing genes hyper
      expressed in the post-diauxic phase. Some of them have already been
      characterized, and many others show similarity to known yeast genes or genes of
      other organisms. However, eleven of them were found to be unrelated to any known
      genes. We have characterized some of these genes as described below. Also, a
      possible cis-element for transcriptional regulation was identified.

PMID- 12501323
TI  - Growth-promoting effect of carbon material upon bacterial cells propagating
      through a distance.
AB  - Carbon material such as graphite and activated charcoal, but not diamond, causes
      the promotion of growth of certain bacteria under ordinarily non-permissive
      stress conditions over a distance of several centimeters. Bacillus carboniphilus
      under the stress of a high KCl concentration and high temperature responded to
      this remote effect of carbon material with enhanced growth, and thermophile
      bacterium Bacillus stearothermophilus responded similarly yet moderately under
      the stress of low temperature. The remote effect of carbon was caused by its
      activation with external energy, probably of electromagnetic nature, as this
      effect was markedly decreased by sheltering the experimental system with an iron
      or aluminum barrier. Carbon material probably transforms the external oscillatory
      pulses or radiation into a signal exerting, far-reaching, growth-promoting effect
      upon cells. The most plausible candidate of signals emitted from carbon was
      considered to be (ultra)sonic.

PMID- 12501324
TI  - Bensingtonia sakaguchii sp. nov. isolated from a leaf of Bischofia javanica in
      the Ogasawara Islands.

PMID- 12501326
TI  - Phylogenetic position of the marine subdivision of Agrobacterium species based on
      16S rRNA sequence analysis.

PMID- 12501325
TI  - Phylogenetic relationships of filamentous cyanobacterial taxa inferred from 16S
      rRNA sequence divergence.

PMID- 12501327
TI  - Effect of six species of white-rot basidiomycetes on the chemical composition and
      rumen degradability of wheat straw.
AB  - This study was conducted to investigate changes in in vitro dry matter
      digestibility (IVDMD), volatile fatty acids (VFA) production and cell-wall
      constituent degradation in wheat straw treated with six white-rot fungi: Daedalea
      quercina, Hericium clathroides, Phelinus laevigatus, Inonotus andersonii,
      Inonotus obliquus, and Inonotus dryophilus. The incubation of wheat straw for 30
      days at 28 C improved IVDMD from 41.4 (control) to 59.2% for D. quercina, 56.3%
      for H. clathroides, 50.2% for P. laevigatus, 51.4% for I. andersonii, 52% for I.
      obliquus, and 55.9% for I. dryophilus. In contrast, the growth of fungi was
      accompanied by the dry matter loss of wheat straw: 43% for D. quercina, 12% for
      H. clathroides, and 22-25% for the other fungi. It is evident that the increase
      in digestibility by D. quercina was not offset by a loss of dry matter. The total
      VFA production during the rumen fermentation of fungus-treated straw was slightly
      increased by H. clathroides and I. dryophilus only. Neutral detergent fiber (NDF)
      and acid detergent fiber (ADF) were reduced in fungus-treated straw. Out of the
      three fractions (hemicellulose, cellulose, and lignin), hemicellulose and lignin
      showed the largest proportionate loss after inoculation with the fungi D.
      quercina, H. clathroides, P. laevigatus, and I. obliquus. The other two fungi
      showed the largest proportionate loss in cellulose and hemicellulose contents.
      The results of this study suggest that the digestion enhancement of wheat straw
      colonized by white-rot fungi is regulated by complex factors including the
      degradation of structural carbohydrates and lignin.

PMID- 12501328
TI  - Chemical analysis of poly-gamma-glutamic acid produced by plasmid-free Bacillus
      subtilis (natto): Evidence that plasmids are not involved in poly-gamma-glutamic
      acid production.
AB  - It has been postulated that the psf gene on a small plasmid, pUH1 (5.8 kb),
      regulates positively the synthesis of capsular poly-gamma-glutamic acid
      (gammaPGA) in Bacillus subtilis (natto) Asahikawa. We found that this strain
      harbored a second plasmid, named pNAGL1 (ca. 50 kb), in addition to pUH1. The
      growth conditions that cure pUH1 or pNAGL1 were established. The plasmid-free
      NAF4 strain derived from B. subtilis (natto) Asahikawa was found to produce
      gammaPGA which was the same as the parent strain in terms of quantity and
      chemical properties having the same molecular mass and content of D-glutamic
      acid. Furthermore, as in the case of the parent cells, the D-glutamic acid in
      gammaPGA, which is known to increase up to ca. 80% of the total glutamic acid as
      Mn(2+) ion concentration increases in growth medium, was found to make up 80% of
      the total glutamic acid of the gammaPGA produced by NAF4 cells grown in the
      presence of 0.1 mm MnCl(2). Thus, these results led us to conclude that the
      plasmids do not encode any gene important for gammaPGA production.

PMID- 12501329
TI  - Cloning of Brn1, a reductase gene involved in melanin biosynthesis in
      Cochliobolus heterostrophus.
AB  - The plant pathogenic fungus Cochliobolus heterostrophus produces melanin, a black
      pigment, via 1, 8-dihydroxynaphthalene. The deficiency of C. heterostrophus Brn1(
      ) mutant was complemented with the cosmid clone pCOS/ML6, screened by
      heterologous hybridization with the genes involved in the melanin biosynthesis of
      Alternaria alternata. We determined the DNA sequence of the Brn1 gene and its
      flanking regions. The Brn1 gene contains one open reading frame consisting of
      three exons separated by two introns. A comparison of the nucleotide and
      predicted amino acid sequence of the Brn1 gene with those of other fungal
      reductase genes involved in melanin biosynthesis indicates significant similarity
      as well as the pathway of melanin biosynthesis.

PMID- 12501330
TI  - Purification and some properties of a thermostable acid esterase from
      Acidiphilium sp. AIU 409.
AB  - Extracellular and cell-bound esterases produced by Acidiphilium sp. AIU 409 were
      homogeneously purified from culture broth and cells, respectively, and some
      properties were investigated. Both esterases more rapidly hydrolyzed p
      nitrophenyl acyl esters containing long-chain fatty acids from C 8:0 to C 18:0
      than those containing short-chain fatty acids from C 2:0 to C 6:0. The Km values
      for p-nitrophenyl long-chain fatty acid esters from C 8:0 to C 18:0 were
      approximately 1.3-1.5 mM. The enzymes were stable at 50 degrees C for 2 days
      between pH 3.0 and 6.5, and optimum pH and temperature were 5.0 and 70 degrees C,
      respectively. Enzyme activity was inhibited by phenylmethylsulfonyl fluoride and
      SDS. The molecular mass of both enzymes was estimated to be approximately 64 kDa
      by SDS-PAGE. The 23 amino acid sequence from the NH(2)-terminus was also the same
      in both enzymes. These results suggest that extracellular esterase might be
      composed of the same components as cell-bound esterase.

PMID- 12501331
TI  - A glutamine synthetase mutant of Saccharomyces cerevisiae shows defect in cell
      wall.
AB  - To study the organization and biosynthesis of the yeast cell wall, hypo
      osmolarity-sensitive mutants of Saccharomyces cerevisiae were analyzed. Cells of
      JS4 were irregular in shape and fragile. Calcofluor staining and quantitative
      analysis indicated that the chitin content was reduced. By DNA cloning and
      genetic analysis, the mutation hpo1-1 was found to be allelic to GLN1 which
      encodes glutamine synthetase. The glutamine content was significantly low in JS4,
      and the mutant was recovered from the cell wall defect by supplying glutamine in
      the medium. Partial inhibition of glutamine synthetase by phosphinothricin also
      induced defects in the cell wall. These results indicate that the shortage of
      glutamine affects cell wall integrity prior to other cellular functions.

PMID- 12501332
TI  - Measurement of in situ halophilic glyceraldehyde-3-phosphate dehydrogenase
      activity from the permeabilized cells of archaebacterium Haloarcula vallismortis.
AB  - The cells of Haloarcula vallismortis, an extreme halophilic archaebacterium, were
      permeabilized by various chemical, physical, and biological treatments.
      Biological permeabilization by lysozyme and papain showed effective results as
      observed by studying the in situ activity of halophilic glyceraldehyde-3
      phosphate dehydrogenase (hGAPDH) as the model enzyme. Detergents N-cetyl-N, N, N
      trimethyl ammonium bromide (CTAB) and digitonin also showed significant results.
      Other strains of halobacteria could also be permeabilized by lysozyme. The cell
      morphology did not show any significant change after permeabilization as observed
      by phase contrast microscopy. The enzyme characteristics of hGAPDH were studied
      in situ using permeabilized H. vallismortis cells. The properties, like optimum
      pH, Km for GAP and NAD(+), inhibition by heavy metals, sulphydryl reagents, and
      other compounds, showed remarkable similarity with those studied in vitro.

PMID- 12501333
TI  - Induction of sexual co-flocculation of heterothallic fission yeast
      (Schizosaccharomyces pombe) cells by mating pheromones.
AB  - Heterothallic fission yeast (Schizosaccharomyces pombe) cells preincubated with
      sex pheromone, P- or M-factor of the obverse mating-type cells, in mannose
      synthetic medium (MSM) results in remarkably increased sexual co-flocculation
      with obverse mating-type cells almost without time lag, i.e., within 10 min. By
      contrast, comparable flocculation requires over 1 h if untreated control cells
      are mixed with obverse mating-type cells. The agglutinin of P cells is more
      inducible than that of M cells. These pheromonal inductions of sexual co
      flocculation are inhibited by the addition of cycloheximide or tunicamycin during
      preincubation but not by chloramphenicol or hydroxyurea. These results
      demonstrate that, in addition to (a) the repression of cell division (G1 arrest)
      and (b) the activation of cell wall autolytic processes (mating-specific
      elongation of cells: formation of their conjugation tubes), mating pheromones of
      fission yeast have another important role; (c) to induce sexual co-flocculation
      (agglutinability). Using our experimental system of preincubation with sexual
      pheromones, we show that M-agglutinin is heat-stable and its induction is
      inhibited by tunicamycin, but that P-agglutinin is heat-labile and its induction
      is only partially inhibited by tunicamycin.

PMID- 12501334
TI  - PCR-amplified ITS length variation within the yeast genus Metschnikowia.

PMID- 12501335
TI  - Characterization of Bradyrhizobium strains isolated from soybean cultivation in
      Thailand.

PMID- 12501336
TI  - Cloning of a gene encoding nisin resistance from Lactococcus lactis subsp. lactis
      M189 which is transcribed from an extended 210 promoter.
AB  - A 56-kb plasmid was identified in Lactococcus lactis subsp. lactis (L. lactis)
      M189 which encodes resistance to nisin (Nis(R)) following mobilization of the
      plasmid into L. lactis LM0230. The Nis(R) determinant was localized on a 1.6-kb
      HindIII fragment by DNA restriction fragment deletion and subcloning. An open
      reading frame (ORF) of 957 bases was identified by sequence analysis and its
      transcription start site was mapped by primer extension. The ORF is flanked by
      two regions which exhibit complete homology to parts of the inverted repeat
      sequences of IS981 and ISS1T. The promoter for transcription was found to consist
      of an extended -10 site (TgTGtTATAAT) that lacks a -35 site. Function of the
      extended -10 promoter was demonstrated by its ability to express the promoterless
      cat gene from Staphylococcus aureus. Base substitution analysis revealed that the
      TgTGt extension is essential for promoter efficiency in L. lactis.

PMID- 12501337
TI  - Cloning and sequence analysis of a plasmid replicon from Lactococcus lactis
      subsp. cremoris FG2.
AB  - A replication region from one of the Lactococcus lactis subsp. cremoris FG2
      plasmids was isolated by cloning of a 4.8-kb XbaI fragment into a replication
      probe vector and transformation into L. lactis LM0230. A 1.8-kb region within
      this fragment was sequenced and confirmed by PCR subcloning to encode a
      functional replicon in LM0230. The replicon consists of an open reading frame
      encoding a putative replication protein (Rep) of 386 amino acids and a non-coding
      region (ori) which features several structural motifs typical of other known
      replication origins, including a 22-bp iteron sequence tandemly repeated three
      and a half times, a 10-bp direct repeat and two sets of inverted repeats. The ori
      region could drive replication of its plasmid when supplied with the replication
      region in-trans. The lack of detectable single-stranded DNA during replication
      and the existence of extensive homology with other known lactococcal theta
      replicons strongly suggest that this region encodes a theta-replicating
      mechanism.

PMID- 12501338
TI  - Evidence for existence of lectins on the ruminal bacteria from steers fed
      roughage and concentrate diets.
AB  - Mixed rumen bacteria, isolated by centrifugation from the rumen of steers fed a
      roughage (R) or concentrate (C) diet, were used to determine if lectins are
      present on rumen bacteria, based on hemagglutination (HA) and HA inhibition
      assays in vitro. Rumen bacteria from steers fed either diet agglutinated
      erythrocytes from cattle, sheep, pigs, and rats, suggested that lectins exist on
      rumen bacteria. Bacterial HA titers from steers receiving the R diet were much
      higher (p<0.001) than those from steers fed the C diet, depending on the
      erythrocyte source used. Centrifugation at 20,000xg for 30 min fractionated the
      rumen bacteria into upper (U) and lower (L) layers. The HA titers of the U
      bacterial fractions were significantly higher (p<0.001) than those of the L
      fractions. A remarkable reduction or complete disappearance of HA titers
      following treatment of rumen bacteria with protease, trypsin, sodium dodecyl
      sulfate (SDS) or sodium periodate indicates that rumen bacterial lectins are
      probably glycoproteins. Lectin specificity for saccharides (galactose, lactose, N
      acetyl-D-galactosamine, methyl-alpha-D-galactopyranoside and methyl-beta-D
      galactopyranoside) and glycoproteins (mucin, fetuin, and thyroglobulin) was found
      in the RU, RL, and CU bacterial fractions; no specific binding was determined in
      the CL fractions. The potential role of lectins in mediating the attachment of
      rumen bacteria to feed particles, rumen epithelia and other microorganisms is
      discussed.

PMID- 12501339
TI  - Phylogenetic relationships of the helical-shaped bacteria in the alpha
      Proteobacteria inferred from 16S rDNA sequences.
AB  - 16S ribosomal RNA gene sequences from seven strains of Aquaspirillum peregrinum,
      Aqu. itersonii, Aqu. polymorphum, and Oceanospirillum pusillum were compared with
      homologous sequences from other members of helical-shaped bacteria. The
      bootstrapped neighbor-joining tree, inferred from 887 aligned sites, placed the
      spirillum taxa assigned to Aquaspirillum, Oceanospirillum, Azospirillum,
      Magnetospirillum, Rhodospirillum, and Rhodocista of the Proteobacteria in seven
      clusters of alpha Proteobacteria separately from other shapes of bacteria. Aqu.
      peregrinum and Aqu. itersonii grouped together in 88% bootstrap support. They
      were more related to Rhodospirillum rubrum and Rsp. photometricum than Aqu.
      polymorphum. Aqu. polymorphum was close to Magnetospirillum gryphiswaldense, Mag.
      magnetotacticum, Rsp. fulvum, and Rsp. molischianum, and more close to Mag.
      gryphiswaldense. Oce. pusillum was not related to other spirillum taxa and was
      placed in a separate branch. Rhodocista was very closely related to Azospirillum.
      Photosynthesis and magnetotaxis, as phenotypic characters, were not important in
      the classification of helical bacteria.

PMID- 12501340
TI  - Biodegradation of the mixture of 2,4,6-trichlorophenol, 4-chlorophenol, and
      phenol by a defined mixed culture.
AB  - Two new strains, Pseudomonas sp. TCP114 degrading 2,4,6-trichlorophenol (TCP) and
      Arthrobacter sp. CPR706 degrading 4-chlorophenol (4-CP), were isolated through a
      selective enrichment procedure. Both strains could also degrade phenol. The
      degradability of one component by a pure culture was strongly affected by the
      presence of other compounds in the medium. For example, when all three components
      (TCP, 4-CP, and phenol) were present in the medium, a pure culture of CPR706
      could not degrade any of the components present. This restriction on
      degradability could be overcome by employing a defined mixed culture of the two
      strains. The mixed culture could degrade all three components in the mixture
      through cooperative activity. It was also demonstrated that the mixed culture
      could be immobilized by using calcium alginate for the semi-continuous
      degradation of the three-component mixture. Immobilization not only accelerates
      the degradation rate, but also enables reuse of the cell mass several times
      without losing the cells' degrading capabilities.

PMID- 12501341
TI  - Hydrolytic dehalogenation of 4-chlorobenzoic acid by an Acinetobacter sp. 
AB  - Acinetobacter sp. strain ST-1, isolated from garden soil, can mineralize 4
      chlorobenzoic acid (4-CBA). The bacterium degrades 4-CBA, starting with
      dehalogenation to yield 4-hydroxybenzoic acid (4-HBA) under both aerobic and
      anaerobic conditions, suggesting that the dehalogenating enzyme in the strain is
      not an oxygenase; the enzyme may catalyze halide hydrolysis. To identify the
      oxygen source of the C(4)-hydroxy groups in the dehalogenation step, we used
      H(2)(18)O as the solvent under anaerobic conditions. When resting cells were
      incubated in the presence of 4-CBA and H(2)(18)O under a nitrogen gas stream, the
      hydroxy group on the aromatic nucleus of the 4-HBA produced was derived from
      water, not from molecular oxygen. This dehalogenation was hydrolytic, because
      analysis of the mass spectrum of the trimethylsilyl derivative of one of the
      metabolites, (18)O-labeled 4-HBA, showed that 80% of the C4-hydroxy groups were
      labeled with (18)O. Hydrolytic dehalogenation of 4-CBA in intact cells has not
      been reported earlier. To identify substrate specificity, we next examined the
      ability of the strain to dehalogenate 4-CBA analogues and dichlorobenzoic acids.
      The results of metabolite analysis by high-pressure liquid chromatography showed
      that the strain dehalogenated 4-bromobenzoic acid and 4-iodobenzoic acid,
      yielding 4-HBA, suggesting that these compounds could be further degraded and
      mineralized by the strain via the beta-ketoadipate pathway, as occurs with 4-CBA.
      This strain, however, did not dehalogenate 4-fluorobenzoic acid, 2- and 3
      chlorobenzoic acids, or 2,4-, 3,4-, and 3,5-dichlorobenzoic acids during 4 days
      of incubation, implying that the dehalogenating enzyme of the strain has high
      substrate specificity.

PMID- 12501342
TI  - Effects of salinomycin and vitamin B(6) on the in vitro synthesis of lysine from
      the stereoisomers of 2,6-diaminopimelic acid by mixed rumen protozoa, bacteria,
      and their mixture.
AB  - An in vitro study was conducted to examine the effects of salinomycin (SL) and
      vitamin B(6) (pyridoxine hydrochloride) (B(6)) on the production of lysine from
      the three stereoisomers of 2,6-diaminopimelic acid (DAP-SI) by mixed rumen
      protozoa (P), mixed rumen bacteria (B), and their mixture (PB). P, B, and PB were
      isolated from the rumen of goats given a concentrate mixture and lucerne cubes,
      separately incubated for 12 h with and without DAP-SI (5 mM) as a substrate and
      SL (5 &mgr;g/ml) and/or B(6) (10 &mgr;g/ml) as additives. In P suspensions, SL
      and B(6) reduced the amount of DAP-SI by 2.1 times (p<0.001, where p is
      probability) and 19.9% (p<0.05), respectively, and also increased the production
      of lysine by 2.4 times (p<0.001) and 26.8% (p <0.05), respectively, during 12 h
      incubation. In B suspensions, the reductions of DAP-SI with a single addition of
      SL or B(6) were 8.5% (p<0.001) and 2.7%, respectively, and lysine production
      increased by 54.3 and 32.9% (p<0.001), respectively, during 12 h incubation. In
      PB suspensions, the reductions of DAP-SI were 21.9 and 11.7% (p<0.001) with a
      single addition of SL or B(6), respectively, and the production of lysine
      increased by 81.4 and 39.4% (p<0.001), respectively, during 12 h incubation. When
      SL and B(6) were added together to the P, B, and PB suspensions, lysine
      production further increased by 12.3, 21.3, and 12.4% more than the cases of
      adding SL only during 12 h incubation, respectively. SL and B(6) were
      demonstrated to enhance the production of lysine from DAP-SI by mixed rumen
      protozoa, mixed rumen bacteria and their mixture in this study.

PMID- 12501344
TI  - The recovery of heat-stressed Vibrio parahaemolyticus in artificial seawater and
      artificial seawater supplemented with chitin microcosms.

PMID- 12501343
TI  - Humicola grisea var. thermoidea cbh1.2: A new gene in the family of
      cellobiohydrolases is expressed and encodes a cellulose-binding domain-less
      enzyme.

PMID- 12501345
TI  - Cloning of a transaminase gene of Citrobacter freundii and the gene dosage effect
      on L-phenylalanine production through transaminase reaction.

PMID- 12501346
TI  - Interspecies hydrogen transfer between the rumen ciliate Polyplastron
      multivesiculatum and Methanosarcina barkeri.

PMID- 12501347
TI  - In vitro metabolism of phenylalanine by ruminal bacteria, protozoa, and their
      mixture.
AB  - An in vitro study was conducted to examine the metabolism of phenylalanine (Phe)
      by mixed rumen bacteria (B), mixed rumen protozoa (P), and a combination of the
      two (BP). Rumen microorganisms were collected from fistulated goats fed lucerne
      cubes (Medicago sativa) and a concentrated mixture twice a day. Microbial
      suspensions were anaerobically incubated at 39 degrees C for 12 h. Phe and some
      other related compounds in both supernatants and microbial hydrolysates of the
      incubations were analysed by HPLC. The net degradation rate (&mgr;mol/g microbial
      nitrogen) of Phe in B was about 1.5-fold higher than that in P. Phe was converted
      mainly into phenylacetic acid (PAA) and unknown compound(s) that presumably
      involved tyrosine in B, P, and BP during the 12 h incubation period. Small
      amounts of benzoic acid (BZA), and traces of phenylpropionic acid (PPR) and
      phenyllactic acid (PLA) were also produced from Phe. PAA production in B was
      found to be higher than that in P, whereas it was significantly higher in BP.
      Although BZA production was less than one-tenth that of PAA production, it was
      higher in P than in B and BP. PPR was detected in both B and BP, but not in P.
      PLA was detected only in B. The production of unknown compound(s) was higher in B
      than in P and BP.

PMID- 12501348
TI  - Synthesis of phenylalanine and production of other related compounds from
      phenylpyruvic acid and phenylacetic acid by ruminal bacteria, protozoa, and their
      mixture in vitro.
AB  - Phenylalanine (Phe) synthesis and the production of other related compounds by
      mixed ruminal bacteria (B), protozoa (P), and a combination of the two mixture
      (BP) in an in vitro system were quantitatively investigated using phenylpyruvic
      acid (PPY) and phenylacetic acid (PAA) as substrates. Rumen microorganisms were
      collected from fistulated goats fed lucerne cubes (Medicago sativa) and a
      concentrated mixture twice a day. Microbial suspensions were anaerobically
      incubated at 39 degrees C for 12 h. Phe and some other related compounds in both
      supernatants and microbial hydrolysates of the incubations were analysed by HPLC.
      A large quantity of Phe was produced from both PPY and PAA not only in B but also
      in P. In B suspensions, free Phe also accumulated in the medium only when PPY was
      used as a substrate. The ability of B to synthesize Phe from both PPY and PAA
      (expressed as unit 'per microbial nitrogen') was 5.1 and 24.8% higher than P,
      respectively. Phe production from PPY in B and P was 43.5 and 55.2% higher than
      that from PAA. Large amounts of PAA (17-27%) were produced from PPY in all
      microbial suspension and production amounts were similar in B and P. Small
      amounts of benzoic acid (BZA) were produced from PPY and PAA in B, P, and BP, and
      higher BZA production was observed in P as compared to B. Phenylpropionic acid
      (PPR) was produced in B from both PPY and PAA, but not in P or BP. A trace amount
      of phenyllactic acid (PLA) was detected only from PPY in B. Higher concentrations
      of an unknown compound from PPY and PAA were found to be accumulated in the body
      protein of B and also in the medium of P, and production of the compound from
      both PPY and PAA was also higher in B than P.

PMID- 12501349
TI  - The rpoD1 gene of Synechococcus sp. strain PCC 7942 encodes the principal sigma
      factor of RNA polymerase.
AB  - RNA polymerase was purified from the unicellular cyanobacterium, Synechococcus
      sp. strain PCC 7942, and found to be associated with a 52 kilodalton (kDa)
      polypeptide. The determined N-terminal sequence of the polypeptide was identical
      to the predicted amino-acid sequence of the rpoD1 gene product. Furthermore, the
      rpoD1 gene is suggested to be indispensable for viability by the inability to
      disrupt the gene. These results indicate that the rpoD1 gene product is the
      principal sigma factor of RNA polymerase.

PMID- 12501350
TI  - Species delimitation in the African Armillaria complex by analysis of the
      ribosomal DNA spacers.
AB  - Thirteen Armillaria isolates, collected from various geographical areas in
      tropical Africa and previously characterized by cultural morphology, pairing
      tests and isozyme analysis, were evaluated using the polymerase chain reaction
      and restriction fragment length polymorphism (PCR-RFLP). DNA regions
      corresponding to the intergenic spacer (IGS) and internal transcribed spacer
      (ITS) were amplified and analyzed by restriction enzyme digestion. The IGS
      amplification products were about 875 bp long and uniform in length among the
      isolates. The amplified-ITS region showed two different lengths corresponding to
      two groups. The first group included the isolates believed to belong to A. mellea
      ssp. africana and two Kenyan isolates (K11 and K12) belonging to a yet unnamed
      biological species. The second group included isolates identified as A. heimii
      and a Tanzanian isolate (T7). Each length variant of the ITS showed distinct RFLP
      banding patterns. Digestion with EcoRI confirmed the two polymorphic groups while
      the endonucleases AluI and NdeII discriminated the A. mellea isolates from the
      Kenyan isolates K11 and K12. In addition, the latter enzyme showed a slight
      dissimilarity between the A. heimii isolates from Western and Eastern Africa (C1
      and Z1). Digestion with HinfI cleaved the isolates of A. heimii into two sub
      groups corresponding to the heterothallic and homothallic forms. This
      endonuclease also indicated that the isolate T7, originating from Tanzania, was
      clearly similar to the heterothallic species A. heimii. Data presented support
      the maintenance of three distinct species of Armillaria in tropical Africa with
      A. heimii as a variable species, the isolates of which were separated in
      accordance with their sexual system. The results indicate that PCR-RFLP can be
      used as a simple and speedy taxonomical tool for the ecological studies of
      Armillaria species.

PMID- 12501351
TI  - Purification of a chitinase from Trichoderma sp. and its action on Sclerotium
      rolfsii and Rhizoctonia solani cell walls.
AB  - Trichoderma harzianum is an effective biocontrol agent of several important plant
      pathogenic fungi. This Trichoderma species attacks other fungi by secreting lytic
      enzymes, including beta-1,3-glucanase and chitinolytic enzymes. Superior
      biocontrol potential may then be found in strains having a high capacity to
      produce these enzymes. We have therefore evaluated the capacity of six
      unidentified Trichoderma spp. isolates to produce chitinolytic enzymes and beta
      1,3-glucanases in comparison with T. harzianum 39.1. All six isolates
      demonstrated substantial enzyme activity. However, while the isolates hereafter
      called T2, T3, T5, and T7 produced lower amounts of enzymes, the activity of
      isolates T4 and T6 were 2-3 fold higher than that produced by T. harzianum 39.1.
      A chitinase produced by the T6 isolate was purified by a single ion-exchange
      chromatography step and had a molecular mass of 46 kDa. The N-terminal amino-acid
      sequence showed very high homology with other fungal chitinases. Its true
      chitinase activity was demonstrated by its action on chitin and the failure to
      hydrolyze laminarin and p-nitrophenyl-beta-N-acetylglucosaminide. The hydrolytic
      action of the purified chitinase on the cell wall of Sclerotium rolfsii was
      convincingly shown by electron microscopy studies. However, the purified enzyme
      had no effect on the cell wall of Rhizoctonia solani.

PMID- 12501352
TI  - Identification of sugar-tolerant yeasts isolated from high-sugar fermented
      vegetable extracts.
AB  - In Japan, high-sugar fermented vegetable extracts are novel functional food
      products for which sugar-tolerant yeasts are employed during processing. In order
      to understand the yeast distribution in these foods and their role in the
      functionality of such foods, we isolated sugar-tolerant yeasts from nine sample
      products, together with one sample each of fermented extract of ume (Japanese
      apricot) and honey. Twenty-three strains were identified as Zygosaccharomyces
      rouxii; one strain as Z. bailii; one strain as Torulaspora delbrueckii; and one
      strain as Candida bombicola. Nearly 90% of the identified strains belonged to Z.
      rouxii with variations in fermentation and assimilation properties. All strains
      grew well on 50% w/w glucose medium, and all but two strains grew on 60% w/w
      glucose medium. Sixteen strains belonged to the strong sugar tolerance type (poor
      or no growth at 1% and maximum growth at 30 or 40% w/w glucose); four strains to
      the moderate type (grew well at 1% and maximum growth at 10 or 20% w/w glucose);
      and seven strains to the weak type (maximum growth only at 1% w/w glucose). One
      strain of Z. rouxii, V19, grew up to 80% (w/w) glucose in liquid medium. In view
      of salt tolerance, only two strains belonged to the moderate type (maximum growth
      at 0.5 or 1 m NaCl); the remaining strains all belonged to the weak type (maximum
      growth only at 0 m NaCl). This suggests that sugar tolerance and salt tolerance
      of yeasts have different aspects.

PMID- 12501353
TI  - Polyamine distribution patterns within the families Aeromonadaceae, Vibrionaceae,
      Pasteurellaceae, and Halomonadaceae, and related genera of the gamma subclass of
      the Proteobacteria.
AB  - Polyamines of the four families and the five related genera within the gamma
      subclass of the class Proteobacteria were analyzed by HPLC with the objective of
      developing a chemotaxonomic system. The production of putrescine, diaminopropane,
      cadaverine, and agmatine are not exactly correlated to the phylogenetic
      genospecies within 36 strains of the genus Aeromonas (the family Aeromonadaceae)
      lacking in triamines. The occurrence of norspermidine was limited but not
      ubiquitous within the family Vibrionaceae, including 20 strains of Vibrio,
      Listonella, Photobacterium, and Salinivibrio. Spermidine was not substituted for
      the absence of norspermidine in the family. Agmatine was detected only in
      Photobacterium. Salinivibrio and some strains of Vibrio were devoid of
      polyamines. Vibrio ("Moritella") marinus contained cadaverine. Within the family
      Pasteurellaceae, Haemophilus contained cadaverine only and Actinobacillus
      contained no polyamine. Halomonas, Chromohalobacter, and Zymobacter, belonging to
      the family Halomonadaceae, ubiquitously contained spermidine and sporadically
      cadaverine and agmatine. Shewanella contained putrescine and cadaverine;
      Alteromonas macleodii, putrescine, 2-hydroxyputrescine, cadaverine, 2
      hydroxyspermidine, and spermidine; Pseudoalteromonas, putrescine, cadaverine, and
      spermidine; Marinobacter, spermidine; and Marinomonas, putrescine and spermidine.
      Their polyamine profiles serve as a chemotaxonomic marker within the gamma
      subclass.

PMID- 12501354
TI  - The effects of Bifidobacterium bifidum OFR9, a strain resistant to
      antituberculosis and antileprosy agents, on fecal flora in mice.
AB  - Since Bifidobacterium bifidum, one of the strains of medical preparations used
      for human intestinal disorders, is sensitive to rifampicin (RFP) and
      fluoroquinolones, its therapeutic effect cannot be guaranteed when it is
      administered concomitantly with these antibiotics. To develop new strains of B.
      bifidum that are resistant to these drugs, B. bifidum RFR61, which is highly
      resistant to RFP, was selected by the N-methyl-N'-nitrosoguanidine (MNNG)
      mutation method. Then, B. bifidum OFR9 was selected in vitro from B. bifidum
      RFR61 by serial passage to increasing concentrations of ofloxacin (OFLX) on a
      solid medium. The minimal inhibition concentrations (MIC) of RFP and
      fluoroquinolones for B. bifidum OFR9 were >256 mg/ml and 16-256 &mgr;g/ml,
      respectively. We investigated the effects of B. bifidum OFR9 on the fecal
      bacterial flora of mice administered with both antibiotics and B. bifidum OFR9.
      The results showed that the concurrent use of B. bifidum OFR9 and antibiotics
      prevented the decrease of bifidobacteria, and quickly restored the flora to
      normal as compared with the use of antibiotic or parent strain therapy alone. The
      survival of Shigella organisms in mouse feces rapidly decreased, and were removed
      within two days as a result of the oral administration of B. bifidum OFR9.

PMID- 12501355
TI  - Molecular characterization of Pasteurella multocida isolates from rabbits.
AB  - Forty isolates of Pasteurella multocida from healthy (17 isolates) and diseased
      (23 isolates) rabbits were assayed for the presence of plasmids in seeking to
      determine whether any correlation exists between the presence of plasmids and
      health status, sensitivity to antimicrobial agents, capsular and somatic type,
      and the anatomic site of isolation. Six isolates were found harboring plasmids. A
      similar ladder pattern ranging from 18 to 3 megadalton (Mda) were found in three
      isolates recovered from diseased rabbits. One band of molecular weight 6.6 Mda
      was shared by four of five (4/5) isolates from the diseased rabbits. No
      correlation was found between the presence of the common plasmids and serotype,
      resistance to antimicrobial agents, and anatomic sites from which the bacteria
      were cultured. Random amplification polymorphic DNA was applied to subtype all
      the isolates of P. multocida. Two single primers were tested for their abilities
      to generate individual fingerprints by using PCR. Primer 1 grouped the isolates
      into 7 profiles, and primer 2 grouped them into 15. Random amplified polymorphic
      DNA-polymerase chain reaction (RAPD-PCR) results show the presence of a wide
      heterogeneity within P. multocida isolates. Therefore RAPD-PCR is an efficient
      technique to detect the DNA polymorphism and could be used to discriminate P.
      multocida of rabbit isolates together with serologic typing.

PMID- 12501356
TI  - Effect of three strains of Pleurotus tuber-regium (Fr.) Sing. on chemical
      composition and rumen fermentation of wheat straw.
AB  - This study was conducted to investigate changes in in vitro dry matter
      digestibility (IVDMD) and cell wall constituent degradation in wheat straw
      treated with 3 strains of the fungus Pleurotus tuber-regium (PT). The incubation
      of wheat straw for 30 days at 28 degrees C improved IVDMD from 30.3% (UWS
      untreated wheat straw) to 47.1% for strain PT1, to 48.5% for PT4, and was
      unchanged IVDMD-29.9% -for PT5. The growth of fungi was accompanied by the dry
      matter loss of wheat straw: 31.5% for PT1, 20.9% for PT4, and 4.8% for PT5.
      Fungal treatment was characterized by increased crude protein and ash contents
      (%) in all fungi-treated straws and reduced hemicellulose and lignin content. It
      is evident that enzymes of all 3 PT strains preferentially degraded hemicellulose
      and lignin over cellulose. Wheat straw treated with PT1 (TWS-PT1), PT4 (TWS-PT4),
      and PT5 (TWS-PT5) and barley (80% : 20%) were used as the experimental diets at
      the fermentation in the artificial rumen. UWS with barley (80% : 20%) served as
      the control diet. The fermentation of experimental diets was accompanied with
      increased IVDMD and a very low degree of hemicellulose degradation. Total gas and
      methane productions were similar in all diets. Moreover, total volatile fatty
      acid (VFA) production (mmol day(-1)), mol % of acetate, propionate, butyrate,
      isobutyrate, and isovalerate were not influenced during the fermentation of
      experimental diets. From the stoichiometric relations, production, utilization,
      and recovery of metabolic hydrogen and organic matter fermented were unchanged.
      Only the recovery of metabolic hydrogen in TWS-PT5 was significantly increased in
      comparison to control diet. Total microbial production showed the tendency of
      lower values in experimental diets, and it was accompanied with a significant
      decrease of ammonia nitrogen (mg L(-1)). Finally the results showed that the
      strains of Pleurotus tuber-regium can improve the quality of wheat straw, but the
      loss of dry matter (DM) (mainly hemicellulose) limits the effective utilization
      of fungi-treated straw in ruminant digestion.

PMID- 12501357
TI  - In vitro degradation of keratin by two species of Bacillus.
AB  - The ability of two species of Bacillus to degrade child's scalp hair, cow horn,
      cow hooves, and human nails in vitro under static conditions was studied by the
      determination of soluble sulphhydryl compounds as cysteine, disulphides as
      cystine, and release of extracellular keratinase along with changes in alkalinity
      of the culture filtrate. Child's scalp hair was found to be the most favored
      keratin substrate for Bacillus spp.

PMID- 12501358
TI  - Effect of nitrogen sources on the activities of lipogenic enzymes in oleaginous
      fungus Cunninghamella echinulata.
AB  - Various inorganic and organic nitrogen sources were used to compare their effects
      on the lipogenesis and the activities of lipogenic enzymes (providing acetyl-CoA
      and donating NADPH) in gamma-linolenic acid-producing fungus Cunninghamella
      echinulata. Lipid accumulation was enhanced by organic nitrogen, among them the
      presence of corn-steep led to almost 40% oil in the biomass. While organic
      nitrogen increased activities of acetyl-CoA carboxylase (ACC) and malic enzyme
      (ME), ATP:citrate lyase (ACL) was rapidly enhanced by ammonium ion. The use of
      NaNO(3) resulted in high activities of glucose 6-phosphate dehydrogenase (GPD)
      and 6-phosphogluconate dehydrogenase (PGD). NADP-isocitrate dehydrogenase (NADP
      ICD) was more active when the fungus utilized all inorganic N-compounds. The rise
      of nitrogen concentration in medium was accompanied with reduced lipid
      accumulation and a fall of ACL, ACC, and ME. In contrast, N-sufficient conditions
      favored biomass growth and elevated activities of GPD and PGD. Kinetic
      experiments also suggest that a significant portion of the required acetyl-CoA
      was being provided via ACL and ACC, and ME (probably coupled with GPD) channeled
      the NADPH into the fatty acid biosynthesis. The contribution of the lipogenic
      enzymes to metabolic pathways other than lipogenesis is also discussed.

PMID- 12501360
TI  - A cytochrome P450 gene cluster in the Rhizobiaceae.

PMID- 12501359
TI  - Taxonomic heterogeneity of strains comprising Gluconacetobacter hansenii.
AB  - The taxonomic standing of Gluconacetobacter hansenii was clarified through
      phenotypic characteristics, quinones, DNA base composition, DNA relatedness, and
      the production of gluconic and ketogluconic acids from glucose. All strains that
      Gossele et al. (Syst. Appl. Microbiol., 4, 338-368, 1983) employed in the
      establishment of Acetobacter hansenii (=G. hansenii) were used in this study.
      Phenotypic differences were shown among the strains of G. hansenii, suggesting
      heterogeneity within the species. The major ubiquinone was Q-10 for all strains
      of G. hansenii, except for strain IFO 3296, which was characterized by Q-9. This
      excluded IFO 3296 from the species G. hansenii and placed it in the genus
      Acetobacter. DNA relatedness revealed four distinct homology groups (I, II, III,
      and IV) among strains of the species. Group I was distinguished from the other
      genomic groups by a lower G1C range from 58.9 to 59.2 mol%. Groups II, III, and
      IV showed higher G+C contents of 60.4 to 62.2, 60.8, and 61.7 mol%, respectively.
      Groups I and IV produced both 2- and 5-ketogluconic acids from glucose, and Group
      III produced only 2-ketogluconic acid. Group II included strains that produced
      both 2- and 5-ketogluconic acids and strains that produced only 2-ketogluconic
      acid. It is clear that G. hansenii consists of genotypically heterogeneous
      strains comprising four homology groups (I, II, III, and IV). Since group I
      contains the type strain (IFO 14820(T)=LMG 1527(T)) of the species, this group is
      designated as the species G. hansenii.

PMID- 12501361
TI  - Detection of methanogenic archaea associated with rumen ciliate protozoa.

PMID- 12501362
TI  - Surface characteristics of lactobacilli isolated from human vagina.
AB  - In the present paper, the taxonomic classification of 134 lactobacilli isolates
      from vaginal samples of 200 women of Tucuman, Argentina, is reported. They were
      clustered in three metabolic groups of the genus Lactobacillus, most belonging to
      the obligately homofermentative group (56%), mainly represented by Lactobacillus
      delbrueckii subsp. delbrueckii and L. acidophilus. In the facultatively
      heterofermentative group (24%), the dominant species were L. paracasei subsp.
      paracasei and L. agilis, and in the obligately heterofermentative group (20%), L.
      brevis was the dominant species. All strains were studied for surface
      characteristics and adhesion-predicting properties. A correlation between the
      methods employed for hydrophobicity testing of the different isolates (Microbial
      Adhesion to Hydrocarbons and Salt Aggregation Test) is reported. Most strains
      were highly hydrophobic. Their hemagglutination capability with human
      erythrocytes was also tested, which was positive only for a few strains. Some
      isolates were self-aggregating. From our results, strains that shared the
      properties assayed were selected for further testing of some other desirable
      characteristics, such as antagonistic substance production, adhesion to
      biological substrates, and appropriate technological properties, to suggest the
      elaboration of a probiotic for the vaginal tract.

PMID- 12501363
TI  - Characterization of high temperature-tolerant rhizobia isolated from Prosopis
      juliflora grown in alkaline soil.
AB  - A method was developed for the fast screening and selection of high-temperature
      tolerant rhizobial strains from root nodules of Prosopis juliflora growing in
      alkaline soils. The high-temperature tolerant rhizobia were selected from 2,500
      Rhizobium isolates with similar growth patterns on yeast mannitol agar plates
      after 72 h incubation at 30 and 45 degrees C, followed by a second screening at
      47.5 degrees C. Seventeen high-temperature tolerant rhizobial strains having
      distinguishable protein band patterns were finally selected for further screening
      by subjecting them to temperature stress up to 60 degrees C in yeast mannitol
      broth for 6 h. The high-temperature tolerant strains were NBRI12, NBRI329,
      NBRI330, NBRI332, and NBRI133. Using this procedure, a large number of rhizobia
      from root nodules of P. juliflora were screened for high-temperature tolerance.
      The assimilation of several carbon sources, tolerance to high pH and salt stress,
      and ability to nodulate P. juliflora growing in a glasshouse and nursery of the
      strains were studied. All five isolates had higher plant dry weight in the range
      of 29.9 to 88.6% in comparison with uninoculated nursery-grown plants. It was
      demonstrated that it is possible to screen in nature for superior rhizobia
      exemplified by the isolation of temperature-tolerant strains, which established
      effective symbiosis with nursery-grown P. juliflora. These findings indicate a
      correlation between strain performance under in vitro stress in pure culture and
      strain behavior under symbiotic conditions. Pure culture evaluation may be a
      useful tool in search for Rhizobium strains better suited for soil environments
      where high temperature, pH, and salt stress constitutes a limitation for
      symbiotic biological nitrogen fixation.

PMID- 12501364
TI  - Quinone profiles in lake sediments: Implications for microbial diversity and
      community structures.
AB  - Microbial quinone compositions of sediment mud samples from five different lakes
      in Japan were studied by spectrochromatography and mass spectrometry. The total
      quinone content of these samples ranged from 1.97 to 18.0 nmol/g dry weight of
      sediment, of which a combined fraction of ubiquinones and menaquinones accounted
      for 42 to 74%. The remaining fraction (26 to 58%) consisted of the photosynthetic
      quinones, plastoquinones and phylloquinone. The sediment samples produced PQ-9 or
      Q-8 as the most abundant quinone type regardless of their geographic locations
      and depths. These results indicate that oxygenic phototrophic microorganisms and
      Q-8-containing proteobacteria constituted major parts of microbial populations in
      the lake sediment. In the surface water of the same sampling sites,
      plastoquinones and phylloquinone occurred in much higher proportions. These
      findings suggested that the high abundance of oxygenic phototrophs in the
      sediment muds resulted from their constant movement or sedimentation from the
      surface water. Numerical analyses of the quinone profiles showed that the
      microbial communities of the sediment were diverse and different in different
      lakes but similar to each other in the diversity of bioenergetic modes. Three
      physiological groups of microbes showing ubiquinone-mediated aerobic respiration,
      oxygenic photosynthesis, and menaquinone-associated respiration were suggested to
      inhabit the lake sediments in balance.

PMID- 12501365
TI  - A phylogenetic study on galactose-containing Candida species based on 18S
      ribosomal DNA sequences.
AB  - Phylogenetic relationships of 33 Candida species containing galactose in the
      cells were investigated by using 18S ribosomal DNA sequence analysis. Galactose
      containing Candida species and galactose-containing species from nine
      ascomycetous genera were a heterogeneous assemblage. They were divided into three
      clusters (II, III, and IV) which were phylogenetically distant from cluster I,
      comprising 9 galactose-lacking Candida species, C. glabrata, C. holmii, C.
      krusei, C. tropicalis (the type species of Candida), C. albicans, C. viswanathii,
      C. maltosa, C. parapsilosis, C. guilliermondii, and C. lusitaniae, and 17 related
      ascomycetous yeasts. These three clusters were also phylogenetically distant from
      Schizosaccharomyces pombe, which contains galactomannan in its cell wall. Cluster
      II comprised C. magnoliae, C. vaccinii, C. apis, C. gropengiesseri, C.
      etchellsii, C. floricola, C. lactiscondensi, Wickerhamiella domercqiae, C.
      versatilis, C. azyma, C. vanderwaltii, C. pararugosa, C. sorbophila, C.
      spandovensis, C. galacta, C. ingens, C. incommunis, Yarrowia lipolytica,
      Galactomyces geotrichum, and Dipodascus albidus. Cluster III comprised C. tepae,
      C. antillancae and its synonym C. bondarzewiae, C. ancudensis, C. petrohuensis,
      C. santjacobensis, C. ciferrii (anamorph of Stephanoascus ciferrii), Arxula
      terrestris, C. castrensis, C. valdiviana, C. paludigena, C. blankii, C.
      salmanticensis, C. auringiensis, C. bertae, and its synonym C. bertae var.
      chiloensis, C. edax (anamorph of Stephanoascus smithiae), Arxula adeninivorans,
      and C. steatolytica (synonym of Zygoascus hellenicus). Cluster IV comprised C.
      cantarellii, C. vinaria, Dipodascopsis uninucleata, and Lipomyces lipofer. Two
      galactose-lacking and Q-8-forming species, C. stellata and Pichia pastoris, and 5
      galactose-lacking and Q-9-forming species, C. apicola, C. bombi, C. bombicola, C.
      geochares, and C. insectalens, were included in Cluster II. Two galactose-lacking
      and Q-9-forming species, C. drimydis and C. chiropterorum, were included in
      Cluster III.

PMID- 12501366
TI  - A phylogenetic study of ubiquinone Q-8 species of the genera Candida, Pichia, and
      Citeromyces based on 18S ribosomal DNA sequence divergence.
AB  - To clarify phylogenetic relationships among species of the anamorphic
      ascomycetous genus Candida with ubiquinone Q-8, we determined complete sequences
      of 18S ribosomal RNA genes (18S rDNAs) from the type strains of 20 species of the
      genus Candida and 7 of the teleomorphic ascomycetous genera Pichia and
      Citeromyces, which have Q-8 as the major ubiquinone. Q-8-forming Candida species
      were divided into six clusters and were phylogenetically distant from a group of
      Candida species that included the type species of the genus. One Q-8-forming
      species from each of the genera Pichia, Citeromyces, or Clavispora was included
      in five of six clusters. Cluster 1 comprised C. ishiwadae, C. ernobii, C.
      karawaiewii, C. anatomiae, C. populi, and Pichia holstii. Cluster 2 comprised C.
      globosa and its teleomorph, Citeromyces matritensis. Cluster 3 comprised C.
      molischiana and Pichia capsulata. Cluster 4 comprised C. silvanorum, C.
      sequanensis, C. fennica, C. entomophila, C. homilentoma, C. rhagii, C. gotoi, and
      Pichia burtonii. Cluster 5 comprised C. fructus, C. musae, and C. lusitaniae
      (anamorph of Clavispora lusitaniae). Cluster 6 comprised C. stellata, C.
      lactiscondensi, C. galacta, and C. incommunis and was a heterogeneous group with
      large interspecific divergence. Pichia pastoris was quite divergent and
      phylogenetically distant from other Pichia species examined. Pichia methanolica
      and its synonym, P. cellobiosa, which have both Q-7 and Q-8 as major ubiquinones,
      were closely associated with Q-7-forming Williopsis salicorniae. Based on this
      comparative analysis of 18S rDNA sequences, it is evident that Q-8 Candida
      species and Q-8 Pichia species are polyphyletic.

PMID- 12501367
TI  - Isolation of a microorganism capable of degrading poly-(L-lactide).
AB  - The isolation of poly-(L-lactide) (PLA)-degrading microorganisms was
      investigated. A PLA-degrading actinomycete, strain No. 3118, was isolated and
      tentatively identified as a member of the genus Amycolatopsis. The optimum
      conditions for degradation of PLA were 43 degrees C at about pH 7 in a mineral
      salt medium with a low concentration of organic nutrients (0.002% yeast extract).
      The original shape of PLA film (Mw=2.3x10(5) after sterilization, 20 &mgr;m
      thick) disappeared within 2 weeks. Lactic acid was detected after the film was
      incubated with culture supernatant.

PMID- 12501368
TI  - Leifsonia gen. nov., a genus for 2,4-diaminobutyric acid-containing actinomycetes
      to accommodate "Corynebacterium aquaticum" Leifson 1962 and Clavibacter xyli
      subsp. cynodontis Davis et al. 1984.
AB  - "Corynebacterium aquaticum" was first proposed by Leifson in 1962 but not
      included in the approved lists of bacterial names in 1980. This species has been
      left from reclassification of the genus Corynebacterium because of the unusual
      chemotaxonomic characteristics such as 2,4-diaminobutyric acid (DAB) in the
      peptidoglycan and menaquinones of MK-10 and MK-11. A close relationship of "C.
      aquaticum" to the genera Agromyces and Rathayibacter has been pointed out from
      the viewpoint of chemotaxonomic profiles and phylogeny based on the 16S rDNA
      sequences. An analysis of DAB isomers of the peptidoglycan distinguished "C.
      aquaticum" clearly from these genera by possessing both L-DAB and D-DAB. We also
      found that the type strain of Clavibacter xyli subsp. cynodontis and two strains
      of amine-decomposing bacteria showed the similar chemotaxonomic features and
      formed a cluster with "C. aquaticum" in the phylogenetic tree based on 16S rDNA
      sequences in the family Microbacteriaceae. Considering these results, we propose
      a new genus Leifsonia to accommodate the four strains. The four species,
      Leifsonia aquatica sp. nov., nom. rev., comb. nov. (type species, type strain=JCM
      1368), Leifsonia shinshuensis sp. nov. (type strain=DB102=JCM 10591), Leifsonia
      naganoensis sp. nov. (type strain=DB103=JCM 10592), and Leifsonia cynodontis
      comb. nov. (type strain=JCM 9733=ICMP 8790), were proposed here for the strains.

PMID- 12501369
TI  - Assignment of the six solvent-producing Clostridium spp. to Clostridium
      beijerinckii based on DNA-DNA reassociation.

PMID- 12501370
TI  - Tryptophan biosynthesis and production of other related compounds from
      indolepyruvic acid by mixed ruminal bacteria, protozoa, and their mixture in
      vitro.
AB  - Tryptophan (Trp) biosynthesis and the production of other related compounds by
      mixed ruminal bacteria (B), protozoa (P), and their mixture (BP) in an in vitro
      system were quantitatively investigated by using 1 mM of indole-3-pyruvic acid
      (IPA) as substrate. Ruminal microorganisms were anaerobically incubated at 39
      degrees C for 12 h. Trp and other related compounds in both the supernatants and
      the microbial hydrolyzates of the incubation were analyzed by HPLC. As a whole,
      about 334, 440, and 436 &mgr;M of Trp were produced from IPA in 12 h by B, P, and
      BP suspensions, respectively. In the B suspension, a greater portion of
      synthesized Trp (242 &mgr;M) from IPA was accumulated as free form in the medium,
      whereas a large amount of Trp (92 &mgr;M) was incorporated into cell protein in a
      12-h incubation. On the other hand, in the P suspension, a large amount of Trp
      (475 &mgr;M) from IPA was also found as free form in the supernatant in a 12-h
      incubation. Protozoa did not incorporate Trp into cell protein, but they
      liberated endogenous Trp (34 &mgr;M) into the medium. The net productions of Trp
      from IPA were 344.3 and 447.7 &mgr;mol/g of microbial nitrogen in 12 h by B and P
      suspensions, respectively. The ability of P to synthesize Trp from IPA was about
      30% higher than that of B in 12 h. Trp produced from IPA by B, P, and BP
      suspensions were simultaneously degraded into its related compounds, and among
      them, indoleacetic acid (IAA) was a major product found in all microbial
      suspensions. Productions of IAA were 124, 25, and 99 &mgr;M from IPA in 12 h by
      B, P, and BP suspensions, respectively. The formation of indolelactic acid (ILA)
      from IPA was observed for the first time in all microbial suspensions, and it was
      about 84, 24, and 54 &mgr;M in 12 h by B, P, and BP, respectively. Higher IAA and
      ILA productions were observed in B when compared with P. A small amount of
      skatole (SKT) (26 &mgr;M) was produced from IPA in B, whereas a sizable amount of
      SKT (38 &mgr;M) was found in BP after a 12-h incubation. p-Cresol (CRL) was also
      produced from IPA by both B (43 &mgr;M) and BP (65 &mgr;M) suspensions in 12 h,
      and this is also the first discovery to show the formation of CRL from IPA by B
      and BP suspensions. BP suspension was more active to produce both SKT and CRL
      from IPA, though P suspension has no ability to produce either SKT or CRL from
      IPA during a 12-h incubation.

PMID- 12501371
TI  - Production of 2-phenylethylamine by decarboxylation of L-phenylalanine in
      alkaliphilic Bacillus cohnii.
AB  - Cellular polyamine fraction of alkaliphilic Bacillus species was analyzed by
      HPLC. 2-Phenylethylamine was found selectively and ubiquitously in the five
      strains belonging to Bacillus cohnii within 27 alkaliphilic Bacillus strains. A
      large amount of this aromatic amine was produced by the decarboxylation of L
      phenylalanine in the bacteria and secreted into the culture medium. The
      production of 2-phenylethylamine may serve for the chemotaxonomy of alkaliphilic
      Bacillus.

PMID- 12501372
TI  - Acid adaptation induces cross-protection against some environmental stresses in
      Vibrio parahaemolyticus.
AB  - The relationship of acid adaptation to the resistance of other environmental
      stresses was examined in Vibrio parahaemolyticus. Acid-adapted cells were found
      to have increased resistance to various stresses, including heat, crystal violet,
      bile, and deoxy cholic acid. However, heat-adapted cells showed no increased
      resistance against acid stress. Adaptation required protein synthesis, since
      treatment with chloramphenicol during adaptation to pH 5.3 prevented the
      development of acid resistance. Acid-adapted cells showed an increased amount of
      outer membrane protein with an apparent molecular weight of 27,000. These results
      show that acid-induced cross-protection involved changes in outer membrane
      protein composition and the known enhancement of intracellular pH homeostasis.

PMID- 12501373
TI  - Partial characterization of a 36-kDa protein from Clostridium botulinum type E
      that inhibits trypsin and chymotrypsin.
AB  - A 36-kDa trypsin inhibitor was purified from Clostridium botulinum type E culture
      supernatant by multiple molecular sieve and ion exchange chromatographic steps.
      The sequence of the amino-terminal 13 amino acid residues of this single-chain
      protein is Asn.Gln.Glu.Val.Phe.Asn.Met.Pro.Lys.Phe.Ser.Thr.Ala-. This novel
      protein that also inhibits chymotrypsin is produced by an organism that does not
      appear to produce any protease.

PMID- 12501374
TI  - Accumulation of anthranilic acid and N-glucosylanthranilic acid by a
      Corynebacterium glutamicum mutant resistant to DL-serine hydroxamate.
AB  - During a study on the effect of DL-serine hydroxamate on Corynebacterium
      glutamicum (JCM1318, a wild strain), a mutant resistant to the drug, strain
      TO3002, was isolated. This mutant accumulated five Ehrlich's reagent positive
      fluorescent substances in the culture medium. Two major and one minor fluorescent
      products were isolated by preparative high-performance liquid chromatography
      following charcoal column chromatography from the culture supernatant. One major
      product was identified as anthranilic acid whose molecular ion was confirmed to
      be 137 by a measurement of liquid chromatography-mass spectrometry (LC-MS), and
      NMR spectrum coincided with that of anthranilic acid. LC-MS spectra of another
      major and the minor product showed that they had the same molecular weight of
      299. This major product was supported to be N-glucosylanthranilic acid (N-o
      carboxyphenyl-1-beta-glucosylamine) by two-dimensional (1)H and (13)C NMR
      analyses. The minor product was speculated to be an Amadori compound derived from
      N-glucosylanthranilic acid. N-Glucosylanthranilic acid accumulated in the early
      phase, then decreased in the late phase of the culture. In contrast, the
      accumulation of anthranilic acid increased remarkably in the late phase of the
      fermentation. Based on this phenomenon, it was assumed that N-glucosylanthranilic
      acid once accumulated was decomposed to form anthranilic acid, at least in large
      part, with the progress of fermentation. The strain TO3002 showed a leaky
      requirement for L-tryptophan or indole (but did not for anthranilic acid) and
      resistance to DL-serine hydroxamate.

PMID- 12501375
TI  - Classification and characterization of lactic acid bacteria isolated from the
      intestines of common carp and freshwater prawns.
AB  - Fifty-four isolates of lactic acid bacteria were obtained from the intestines of
      the common carp (Cyprinus carpio) and freshwater prawns (Macrobrachium
      rosenbergii) in Nakorn-Pathom Province, Thailand. All isolates were Gram-positive
      and catalase-negative cocci that did not produce gas from glucose and formed dl
      or L(+) lactic acid only. Most isolates were able to grow in broth at pH 9.6, in
      6.5% NaCl (w/v) and 40% (w/v) bile. These isolates were divided into six groups
      (A-F) by sugar fermentation patterns. Strains in the groups A, B, C, and D showed
      intergroup DNA homology values of above 73.8%, indicating that these groups were
      composed of a single species. Following phylogenetic analysis, strains E 1, E 7,
      and E 26 from groups A, E, and F were placed in the clusters of the genera
      Lactococcus, Pediococcus, and Enterococcus, respectively. The type strains of
      Lactococcus garvieae, Pediococcus acidilactici, and Enterococcus faecium were the
      most closely related species with E 1, E 7, and E 26 in the phylogenetic tree,
      respectively. The DNA-DNA hybridization results indicated that strains in groups
      A (including groups B, C, and D), E, and F could be identified as belonging to
      the species Lactococcus garvieae, Pediococcus acidilactici, and Enterococcus
      faecium, respectively. Lactococcus garvieae was the dominant member of the
      population, accounting for 90.7% of the isolates.

PMID- 12501376
TI  - Utilization of nitriles by yeasts isolated from a Brazilian gold mine.
AB  - Yeast strains from the genera Candida, Debaryomyces, Aureobasidium, Geotrichum,
      Pichia, Rhodotorula, Tremella, Hanseniaspora, and Cryptococcus were isolated from
      samples of a gold mine from liquid extraction circuit. These strains were tested
      for their ability to utilize acetonitrile at 12 mM as the sole nitrogen source.
      The yeasts that grew using acetonitrile at 12 mM were tested in the presence of
      acetonitrile, isobutyronitrile, methacrylnitrile, and propionitrile at
      concentrations of 12, 24, 48, 97, and 120 mM. One strain was selected for each
      nitrile and the concentration of nitrile in which the best growth occurred.
      Cryptococcus sp. strain UFMG-Y28 had a better growth on 120 mM propionitrile and
      97 mM acetonitrile, Rhodotorula glutinis strain UFMG-Y5 on 48 mM
      methacrylnitrile, and Cryptococcus flavus strain UFMG-Y61 on 120 mM
      isobutyronitrile. The utilization of different nitriles and amides by yeast
      strains involves hydrolysis in a two-step reaction mediated by both inducible and
      intracellular nitrile hydratase and amidase.

PMID- 12501377
TI  - Nonuniversal usage of the leucine CUG codon in yeasts: Investigation of
      basidiomycetous yeast.

PMID- 12501378
TI  - Polygalacturonase production of Rhizopus sp. MKU 18 using a metal-ion-regulated
      liquid medium.

PMID- 12501379
TI  - Production of alkaline protease by a genetically engineered Aspergillus oryzae
      U1521.
AB  - The production of alkaline protease of Aspergillus oryzae U1521 was examined in
      liquid culture. In a culture of defatted soybean only, it gave satisfactory
      enzyme yields at 584,000 U/g defatted soybean. When various carbohydrates were
      supplemented, enzyme production was significantly increased. An increase in
      production by lactose was the most marked. Enrichment with casitone or casein
      increased productivity, but not cornsteep solid. Media formulation (g/L) of
      defatted soybean 10, lactose 5, casitone 1, and KH(2)PO(4) 5 enhanced alkaline
      protease production by A. oryzae U1521 to a maximum of 1,410,000 U/g defatted
      soybean. Scaling-up experiments indicated the flask-scale results could be
      reproduced at 40 g of substrate in 5-L fermenter. The enzyme activity was maximum
      between pH 8-9 and at a temperature of 45 degrees C.

PMID- 12501380
TI  - A new type of flagellin gene in Pseudomonas putida.
AB  - Previously established PCR amplification and Southern hybridization procedures
      were developed for the isolation of the 0.8-kb flagellin gene in Pseudomonas
      putida. The deduced protein sequence has significant homology to the N- and C
      terminal sequences of other bacterial flagellins. We propose that P. putida
      flagellin genes can be divided at least into three size groups: type I (2.0 kb),
      type II (1.4 kb), and type III (0.8 kb). Type I and type II flagellin genes have
      been reported. The new 0.8-kb type III gene was expressed in E. coli, and the
      resulting protein was purified and used to raise polyclonal antibody to study
      whether this small gene encodes flagellin. The antiserum reacted with purified
      flagellin monomers from representatives of each flagellin type, as well as
      proteins of the same sizes in lysates of these organisms, on Western immunoblots.
      This antiserum was determined to be functional in a motility inhibition assay.
      Similar results were obtained from antiserum directed against purified type III
      flagellin, indicating that a new type of flagellin gene in P. putida has been
      found. Preliminary electron microscopic study revealed that P. putida isolate
      with the smaller flagellin gene type appeared to have a thinner flagellar
      filament.

PMID- 12501381
TI  - Effect of citric acid on the biosynthesis and composition of xanthan.
AB  - The effect of citric acid metabolism by Xanthomonas campestris on composition of
      xanthan has been studied. Citric acid consumption in fed-batch and continuous
      fermentation increased the pyruvic acid content of xanthan. An increase in
      pyruvic acid content in xanthan has been explained with the help of energy
      balance in xanthan biosynthesis.

PMID- 12501382
TI  - Uptake of free and complexed silver ions by yeasts isolated from a gold mining
      industry in Brazil.

PMID- 12501383
TI  - Substrate specificities in triacylglycerol-secretion by the yeast, Trichosporon
      sp. 

PMID- 12501384
TI  - Photosynthetic regulatory gene cluster in an aerobic photosynthetic bacterium,
      Roseobacter denitrificans.

PMID- 12501385
TI  - Thermal transition profiles of bacteriophage T4 and its DNA.

PMID- 12501386
TI  - Improved staining method for detecting Cryptosporidium oocysts in stools using
      malachite green.

PMID- 12501387
TI  - A new rapid method of glycolate test by diethyl ether extraction, which is
      applicable to a small amount of bacterial cells of less than one milligram.
AB  - The glycolate test is a method to discriminate N-acyl groups of muramyl residue
      in peptidoglycan of bacterial cell walls by color reaction without purification
      of the cell walls. The glycolyl residue presents red purple color by heating with
      0.02% 2,7-dihydroxynaphthalene (DON) dissolved in concentrated H(2)SO(4). Instead
      of the previous column methods for quantitative analysis, a qualitative method by
      solvent works was developed to simplify and to miniaturize the analysis. In this
      method, solvents played two roles, removal of interfering materials and
      extraction of glycolic acid from the cell hydrolysates. Of several solvent
      systems tested, diethyl ether was studied in detail on such properties as the
      efficiency of glycolic acid extraction under several conditions, the ability of
      removing various interfering compounds, and the advantage on evaporation
      procedure of the solvent from extracts. DON reaction of the second diethyl ether
      extract from cell hydrolysate of "Micromonospora nigra" JCM 3328 showed a clear
      red purple color of a strong absorbance at 530 nm, which is the same as that of
      authentic glycolic acid. The solvent method was applied to 20 strains of typical
      actinomycete species whose acyl types have already been known (Uchida and Seino,
      1997). All glycolate test positive strains showed the clear red purple color
      mentioned above, whereas acetyl type strains revealed no apparent color by the
      same procedures. Additional experiments indicated that the glycolate test could
      be determined with less than 1 mg of actinomycete cells by using a smaller amount
      of DON reagent and ordinary polypropylene tubes. The new method was discussed for
      advantages in the identification of actinomycetes and for possible applications
      to other fields.

PMID- 12501388
TI  - Molecular cloning, expression, and characterization of an endo-beta-1,4-glucanase
      cDNA from Epidinium caudatum1.
AB  - An endo-beta-1,4-glucanase gene (epi3) from the rumen ciliated protozoan
      Epidinium caudatum was cloned from a cDNA library constructed by using the lambda
      ZAP II vector. The enzymatic activity of the gene product was detected by the
      Congo red assay, using carboxymethyl cellulose (CMC) as substrate. The nucleotide
      sequence of epi3 revealed 1,253 nucleotides with an open reading frame for a
      protein (Epi3) of 356 amino acids (Mr -41,014). Epi3 shows high homology with
      family 5 endoglucanase genes and with genes from protozoa isolated from sources
      other than the rumen. The specific activity of Epi3 produced in Escherichia coli
      was 5.544, 2.754, and 0.295 mmol of glucose min(-1) mg(-1) protein when the
      substrates used were CMC, beta-glucan, and xylan, respectively. A beta-1,4-linked
      trisaccharide of glucose was the preferred substrate of Epi3, as determined by
      analysis with the p-nitrophenyl form of the substrate. To our knowledge, this is
      the first report of the isolation of an endoglucanase gene from a rumen
      protozoan.

PMID- 12501389
TI  - Transformation with green fluorescent protein of Trichoderma harzianum 1051, a
      strain with biocontrol activity against Crinipellis perniciosa, the agent of
      witches'-broom disease of cocoa.
AB  - A plasmid vector for fungal expression of an enhanced, red-shifted variant of the
      Aequoria victoriae green fluorescent protein was constructed by fusion of the
      EGFP gene to the highly expressed Aspergillus nidulans gpd promoter and the A.
      nidulans trpC terminator. This construction was introduced by cotransformation,
      using benomyl selection, into Trichoderma harzianum strain 1051, a strain being
      evaluated for the biological control of witches'-broom disease of cocoa caused by
      Crinipellis perniciosa. Epifluorescence microscopy was used to monitor
      germination and attachment of stable transformant conidia on the surface of C.
      perniciosa hyphae.

PMID- 12501390
TI  - Oxidation of chlorinated olefins by Escherichia coli transformed with dimethyl
      sulfide monooxygenase genes or cumene dioxygenase genes.
AB  - In the present work, it was shown that the dimethyl sulfide (DMS) monooxygenase
      and the cumene dioxygenase catalyzed oxidation of various chlorinated ethenes,
      propenes, and butenes. The specific activities of these oxygenases were
      determined for C(2) to C(4) chlorinated olefins, and the oxidation rates ranged
      from 0.19 to 4.18 nmol.min(-1).mg(-1) of dry cells by the DMS monooxygenase and
      from 0.19 to 1.29 nmol.min(-1).mg(-1) of dry cells by the cumene dioxygenase. The
      oxidation products were identified by gas chromatography-mass spectrometry. Most
      chlorinated olefins were monooxygenated by the DMS monooxygenase to yield
      chlorinated epoxides. In the case of the cumene dioxygenase, the substrates
      lacking any chlorine atom on double-bond carbon atoms were dioxygenated, and
      those with chlorine atoms attaching to double-bond carbon atoms were
      monooxygenated to yield allyl alcohols.

PMID- 12501391
TI  - Genetic relatedness among species in Aspergillus section Clavati as measured by
      electrophoretic comparison of enzymes, DNA base composition, and DNA-DNA
      hybridization.
AB  - Aspergillus subgenus Clavati has four recognized species: A. clavatus (the type
      species), A. clavatonanicus, A. giganteus, and A. longivesica. These species are
      strictly anamorphic (mitotic) and defined by the morphological species concept.
      However, their genealogical relationships remain uncertain. In this study, we
      examined the genetic relatedness among the four species in this section, using
      electrophoretic comparison of enzymes, DNA base composition, and DNA-DNA
      hybridization. In a dendrogram based on the calculated similarity values of four
      enzymes, 10 strains in section Clavati, 3 strains in the xerophilic species, a
      strain in section Ornati, and a strain in section Cremei were separated into nine
      major clusters at a 60% similarity level. A. longivesica JCM 10186(T) had Q-10 in
      our analysis, but Kuraishi et al. (1990) reported A. longivesica JCM 1720(T) had
      Q-9 (49%) and Q-10 (46%). The G+C contents of the four species of section Clavati
      ranged from 48 to 50 mol%. The degree of the intraspecific reassociation among
      the DNAs from the strains of these species ranged from 77 to 99%, whereas the
      degrees of interspecific relative binding among strains of the four species
      ranged from 30 to 59%. Our data from enzyme patterns and DNA relatedness support
      the validity of the three species in section Clavati, except for A. longivesica.

PMID- 12501392
TI  - Effects of microbes on color changes of red lead in murals.

PMID- 12501393
TI  - Isolation of centromeric DNA from Saccharomyces bayanus.

PMID- 12501394
TI  - cDNA cloning of bilirubin oxidase from Pleurotus ostreatus strain Shinshu and its
      expression in Aspergillus sojae: an efficient screening of transformants, using
      the laccase activity of bilirubin oxidase.

PMID- 12501395
TI  - Isolation and characterization of triacylglycerol-secreting mutant strain from
      yeast, Saccharomyces cerevisiae.
AB  - To establish the molecular bases for development of a microbiological system
      approaching excretive fermentation of useful lipids, a mutant strain that
      accumulates lipids in the medium was isolated from the laboratory yeast
      Saccharomyces cerevisiae. Following the mutagenesis to strain YP1, a long chain
      fatty acid utilizer with ethylmethane sulfonate, the mutant strain, STG1, was
      selected from about 80,000 colonies. The analysis of extracellular lipids and the
      monitoring of leakage of intracellular proteins indicated that strain STG1
      secreted lipids containing triacylglycerols into the extracellular space without
      cell lysis. Genetic studies clarified that this mutation was recessive and was
      complemented by wild-type genomic DNA fragments. STG1 was considered to be a good
      tool for elucidation of the molecular mechanism for transmembrane lipid
      transport.

PMID- 12501396
TI  - Differentiation of Gluconacetobacter liquefaciens and Gluconacetobacter xylinus
      on the basis of DNA base composition, DNA relatedness, and oxidation products
      from glucose.
AB  - Gluconacetobacter liquefaciens and Gluconacetobacter xylinus share very similar
      phenotypic characteristics. They are differentiated by the production of a
      reddish-brown water-soluble pigment of the former and cellulose production of the
      latter. However, the loss of the two distinguishing features questions the
      separate standings of the two species. The DNA base composition and the DNA
      relatedness of strains of the two species, including other established species of
      acetic acid bacteria, were determined. G. liquefaciens strains had the higher
      guanine-plus-cytosine content (G+C content) in DNA, ranging from 63.5 to 66.9
      mol%, and G. xylinus had the lower range, from 59.4 to 63.2 mol%. DNA
      hybridization revealed a low level of DNA similarity between the two species. G.
      liquefaciens strains produced 2,5-diketogluconic acid and pyrones from glucose,
      and G. xylinus strains produced 5-ketogluconic acid. From these results, it is
      unequivocal that G. liquefaciens is a distinct species from G. xylinus.

PMID- 12501397
TI  - Evaluation of yeast extracts as growth media supplements for lactococci and
      lactobacilli by using automated spectrophotometry.
AB  - An automated spectrophotometric (AS) method was used to evaluate the growth
      promoting ability of yeast extracts (YE) on cultures of Lactobacillus acidophilus
      and Lactococcus lactis subsp. cremoris. The AS data were compared to that
      obtained from classical shake flask fermentations and from 250 ml bioreactors
      equipped with pH control. In assays involving the evaluation of 26 different
      commercial YE, maximum growth rate (&mgr;(max)) values determined with the AS
      unit ranged from 0.25 to 0.45 h(-1) for Lb. acidophilus and from 0.10 to 0.40 h(
      1) for Lc. cremoris. Good correlations were obtained between AS data and manual
      sampling from the shake flasks or the bioreactors for mmax, as well as maximum
      optical density (OD(max)). The AS method is thus useful as a screening tool for
      the selection of YE lots in media formulation. Species reacted differently to the
      26 YE, but less variation was observed between strains of the same species. This
      suggests that a producer of various lactococci or lactobacilli can expect a
      relatively constant response to a given YE lot between strains of the same
      species. However, it should not be assumed that the YE having the best growth
      promoting properties for Lb. acidophilus will also be the best media supplements
      for the growth of Lc. cremoris.

PMID- 12501398
TI  - Identification of acetic acid bacteria isolated from Indonesian sources,
      especially of isolates classified in the genus Gluconobacter.
AB  - Sixty-four strains of acetic acid bacteria were isolated from Indonesian sources
      such as fruits, flowers, and fermented foods by the enrichment culture at pH 3.5.
      Forty-five strains were routinely identified as Acetobacter strains because of
      their oxidation of acetate and lactate to carbon dioxide and water and their Q-9
      isoprenolog, corresponding to 70% of all the 64 acetic acid bacteria isolated.
      Eight isolates were identified as Gluconacetobacter strains because of their
      oxidation of acetate and lactate and their Q-10 isoprenolog, occupying 13% of all
      the isolates. The remaining 11 isolates, accommodated in the genus Gluconobacter
      because of no oxidation of acetate and lactate and because of their Q-10
      isoprenolog, accounted for 17% of all the isolates. They were divided into two
      groups based on DNA base compositions. One comprised the seven isolates, which
      had high G1C contents of DNA ranging from 60.3 to 63.5 mol% and of which DNAs
      hybridized with that of the type strain of Gluconobacter oxydans at values of 64
      94% of DNA relatedness. The other comprised the remaining four isolates, which
      had low G+C contents of DNA ranging from 57.5 to 57.7 mol% and of which DNAs
      hybridized with that of the type strain of Gluconobacter frateurii at values of
      63-77% of DNA relatedness. The high values of DNA relatedness, 84 to 96%, were
      obtained between the type strains of Gluconobacter cerinus and Gluconobacter
      asaii.

PMID- 12501399
TI  - Identity of the xerophilic species Aspergillus penicillioides: Integrated
      analysis of the genotypic and phenotypic characters.
AB  - We examined the identity of Aspergillus penicillioides, the typical xerophilic
      and strictly anamorphic species, using an integrated analysis of the genotypic
      and phenotypic characters. Our experimental methods on two genotypic characters,
      i.e., DNA base composition using the HPLC method and DNA relatedness using the
      nitrocellulose filter hybridization technique between A. flavus, A. oryzae, and
      their close relations revealed a good agreement with the values by buoyant
      density (for DNA base composition) and spectrophotometric determination (for DNA
      relatedness) reported by Kurtzman et al. in 1986. On the basis of these
      comparisons, we examined DNA base composition and DNA relatedness of six selected
      strains of A. penicillioides, including IFO 8155 (originally described as A.
      vitricola), one strain of A. restrictus, and the respective strains from Eurotium
      amstelodami, E. repens, and E. rubrum. As a result, five strains within A.
      penicillioides, including the neotype strain NRRL 4548, had G+C contents of 46 to
      49 mol%, whereas IFO 8155 had 50 mol%. A. restrictus had 52 mol%, and three
      Eurotium species ranged from 46 to 49 mol%. The DNA relatedness between A.
      penicillioides (five strains), except for IFO 8155, exhibited values greater than
      70%, but the DNA complementarity between four strains and IFO 8155 in A.
      penicillioides revealed values of less than 40%. DNA relatedness values between
      three species of Eurotium were 65 to 72%. We determined 18S, 5.8S, and ITS rDNA
      sequences as other genotypic characters from A. penicillioides (six strains), A.
      restrictus, and related teleomorphic species of Eurotium. In three phylogenetic
      trees inferred from these sequences, five strains of A. penicillioides, including
      the neotype strain, were closely related to each other, whereas IFO 8155 was
      distantly related and grouped with other xerophilic species. Our results have
      suggested that A. penicillioides typified by NRRL 4548 and A. penicillioides IFO
      8155 (ex holotype of A. vitricola) are not conspecific. The enzyme patterns as a
      genotypic character and general morphology and conidial ornamentation types as
      phenotypic characters supported this conclusion. Therefore the name A. vitricola
      Ohtsuki, typified by the holotype strain IFO 8155, should be revived.
      Evolutionary affinities among Aspergillus species and related teleomorphs,
      including the xerophilic taxa, are discussed.

PMID- 12501400
TI  - A new structural type of methionaquinones isolated from hot spring sulfur-turf
      bacterial mats.

PMID- 12501401
TI  - Isolation of Methanobrevibacter sp. as a ciliate-associated ruminal methanogen.

PMID- 12501402
TI  - Salt stress sensitivity of nitrogen fixation in Enterobacter agglomerans strains.
AB  - Two strains 333 to 339 of Enterobacter agglomerans were selected in the present
      study to evaluate the response of increasing concentrations of NaCl on growth,
      N(2)-fixation, and nitrogenase activity/synthesis. E. agglomerans strains 333 and
      339 showed optimum growth and acetylene-reducing activity with 0.5 to 1.0% NaCl
      in a nitrogen-free minimal medium (NFDM) with glucose, respectively, in 28 h
      incubation, although both strains displayed better growth and acetylene-reducing
      activity with 3.0% and 2.0% NaCl after 52 h and 100 h incubation periods than the
      28 h culture did. Our experiments with shiftings of salt concentrations in NFDM
      medium indicated that a synthesis of nitrogenase enzyme was generally more
      sensitive to higher concentrations of NaCl than nitrogenase activity was.

PMID- 12501403
TI  - The ratio of L-form to D-form of lactic acid as a criteria for the identification
      of lactic acid bacteria.
AB  - Stereoisomers of lactic acid produced by lactic acid bacteria were determined by
      HPLC by using an enantiomeric resolution column. In general, the ratios of L-form
      to D-form (the type of stereoisomer) obtained were compared with those in
      references. Values of the type of stereoisomer of lactic acid were discussed from
      the viewpoint of identification of lactic acid bacteria.

PMID- 12501404
TI  - A comparison of features and the microbial constitution of the fresh feces of
      pigs fed diets supplemented with or without dietary microbes.
AB  - The features and the constitution of the microbial population of fresh feces were
      compared between pigs fed a diet supplemented with dietary microbes and pigs
      given nonsupplemented diets. The former were reared on farm C and the latter on
      farms A and B. The concentrations of ammonia-N, indole, and skatole of fresh
      feces were not significantly different between pigs reared on farm C and those
      raised on farms A and B, but the concentrations of ammonia-N and the skatole of
      fresh feces were significantly different between pigs reared on farms A and B.
      The total VFA (volatile fatty acids) concentration of fresh feces in pigs on farm
      C was slightly lower than in those on farms A and B. Moreover, the molar
      proportion of the acetic acid in feces in pigs on farm C was lower; inversely,
      that of propionic and butyric acids was higher in comparison with those on farms
      A and B. No differences were evident in the total viable counts of feces among
      pigs reared on the three different farms. Clostridium perfringens was abundant in
      feces of pigs raised on farms A and B, but it was not detected in pigs reared on
      farm C. Megasphaerae, bifidobacteria, and clostridia except for C. perfringens
      were more abundant in the feces of pigs fed a diet supplemented with dietary
      microbes on farm C, compared with pigs given the nonsupplemented diets on farms A
      and B.

PMID- 12501405
TI  - Synthesis and secretion of phosphatases by endophytic isolates of Colletotrichum
      musae grown under conditions of nutritional starvation.
AB  - Even though fungal phosphatases are widely used to study ambient-regulated gene
      expression, little is known about these enzymes in the agriculturally important
      genus Colletotrichum. We have therefore identified several phosphatase activities
      in endophytic isolates of Colletotrichum musae grown under conditions of
      nutritional sufficiency or starvation for sources of phosphorus (P), nitrogen
      (N), carbon (C), and sulphur (S). These enzyme forms could be distinguished by
      substrate specificity, optimum pH, activation and inhibition by some substances,
      response to nutritional starvation, and pattern of migration in native gel
      electrophoresis. At least four individual phosphatase activities were identified
      under the growth conditions employed. A pH 5.0 acid phosphatase and an Mg(2+)
      dependent pH 7.5 phosphodiesterase were expressed under all growth conditions at
      constant rates. Under conditions of P-starvation, derepression of a major pH 6.0
      acid phosphatase was observed in cell-free extracts and the culture medium. A
      synthesis of alkaline phosphatase activities followed a more distinct pattern.
      Under conditions of nutritional sufficiency of P- or N-starvation, only a single
      intracellular enzyme form (optimum pH 10) was observed, which was resolved as a
      single electrophoretic activity band. However, in media lacking C or S sources
      additional alkaline phosphatase forms were derepressed with a concomitant
      increase in the overall enzyme activity level measured at pH 10. To our
      knowledge, this report represents the most detailed study of phosphatases in
      Colletotrichum and the first partial characterization of the phosphatase system
      in an endophytic fungus.

PMID- 12501406
TI  - Study on the production of acetyl esterase and side-group cleaving glycosidases
      of ammonia fungi.
AB  - Acetyl esterase was found to be widely distributed in ammonia fungi in a screen
      comprising 26 species (71 strains). No great differences appeared in enzyme
      production for acetyl esterase, beta-xylosidase, alpha-arabinosidase, or beta
      glucosidase between different strains of the same species, but differences were
      detected between different genera. Acetyl esterase of Coprinus phlyctidosporus
      and Lyophyllum tylicolor may act cooperatively with beta-glucosidase. An increase
      in urea concentration significantly affected enzyme activity. It was supposed
      that urea used as 20 mg/g litter may solubilize leaf nutrients. At 20 mg urea
      added/g litter, a sizable increase in beta-glucosidase activity of C.
      phlyctidosporus and L. tylicolor was found, whereas a decrease in enzyme
      production of alpha-arabinosidase and beta-xylosidase was detected in some
      strains. Acetyl esterase and beta-glucosidase of C. phlyctidosporus, L.
      tylicolor, C. leucocephala 589, and C. rhombisperma 248 were most active in
      acidic conditions (pH 5.3-6.3), whereas acetyl esterase of L. nuda 561 and L.
      tarda 564 was most active in alkaline conditions (pH 8.3).

PMID- 12501407
TI  - Restriction analysis of the ITS region for characterization of the Debaryomyces
      species.
AB  - The internal transcribed spacer (ITS) region of rDNA was used for taxonomic
      inferences in ascomycetous yeasts. The Debaryomyces species had a 640-690 ITS
      size. The analyzed Candida species can be differentiated by its distinct ITS
      size. The enzymatic digestion of the ITS region show large homogeneity in
      Debaryomyces, with polymorphism for only two enzymes. The ITS size and the
      enzymatic restriction method were used in Brazilian isolates, detecting some
      Debaryomyces misidentifications in cultures previously identified by conventional
      methods.

PMID- 12501408
TI  - Enhanced production of extracellular ice nucleators from Erwinia herbicola.
AB  - The effects of growth conditions and chemical or physical treatments on the
      production of extracellular ice nucleators (ECINs) by Erwinia herbicola cells
      were investigated. The spontaneous release of ECINs, active at temperatures
      higher than -4 degrees C, into the environment depended on culture conditions,
      with optimal production when cells were grown in yeast extract to an early
      stationary phase at temperatures below 22 degrees C. ECINs were vesicular,
      released from cell surfaces with sizes ranging from 0.1 to 0.3 &mgr;m as
      determined by ultrafiltration and transmission electron microscopy. Protein
      profiles of ECIN fractions during bacterial growth were examined by SDS
      polyacrylamide gel electrophoresis (SDS-PAGE), and Ina proteins were detected by
      Western blotting. ECIN production was enhanced 5-fold when cells were treated
      with EDTA and 20- to 30-fold when subjected to sonication. These conditions
      provide a means for large-scale preparationage> ECINs by E. herbicola.

PMID- 12501409
TI  - Simultaneous degradation of p-nitrophenol and phenol by a newly isolated
      Nocardioides sp. 
AB  - A p-nitrophenol (PNP)- and phenol-mineralizing bacterium (strain NSP41) was
      isolated from an industrial wastewater and identified as a member of the genus
      Nocardioides. PNP was degraded via a hydroquinone pathway, and phenol was
      degraded through a catechol pathway in strain NSP41. Both enzyme systems for the
      degradation of PNP and phenol were induced simultaneously in the presence of both
      compounds. Although both enzyme systems were induced at the same time, PNP and
      phenol were degraded by the hydroquinone and catechol pathway, respectively.
      However, during the simultaneous degradation in the low phenol concentration,
      after the exhaustion of phenol, some PNP was transformed by the catechol pathway
      and 4-nitrocatechol was transiently accumulated. Kinetically, the addition of
      phenol greatly enhanced the apparent PNP degradation rate, which may be due to
      the increased cell mass by the assimilation of phenol.

PMID- 12501410
TI  - Specific probiotic characterization of Weissella hellenica DS-12 isolated from
      flounder intestine.
AB  - A total of 199 microorganisms were isolated from the intestinal contents of
      flounder (Paralichthys olivaceus) in a fish farm in Seoul, Korea. Among these
      strains, DS-12 was selected as a candidate for flounder probiotics because of its
      excellent exhibition of antimicrobial activity against fish pathogens such as
      edwardsiella, pasteurella, aeromonas, and vibrio, and initiate growth in 10%
      NaCl, 10% bile, and in broth at pH 3 for 90 min. This strain was Gram-positive,
      and catalase-negative coccoid rods that produced gas from glucose and formed more
      than 90% of lactate as the D(-) isomer. This organism is positioned at a cluster
      in the genus Weissella on the phylogenetic tree based on 16S rRNA sequences,
      which were assigned to Weissella hellenica on the basis of DNA-DNA relatedness.
      However, the type strain of W. hellenica JCM 10103(T) had no antibacterial
      activity against the fish pathogenic bacteria and was found to be quite different
      from the DS-12 strain in some sugar fermentation patterns of alpha-methyl-D
      glucoside, esculine, cellobiose, melibiose, D-raffinose, and D-turanose, being
      especially unable to grow at 15 and 35 degrees C in 7% NaCl and 10% bile. The
      results obtained in the present study demonstrated that the type strain of W.
      hellenica had no probiotic characteristics, but the strain DS-12 could be used as
      a specific probiotic for flounder.

PMID- 12501411
TI  - Molecular characterization of the operon comprising the spoIV gene of Bacillus
      megaterium DSM319 and generation of a deletion mutant.
AB  - According to sequence analysis, the spoIV-locus of Bacillus megaterium DSM 319 is
      1,185 bp long; it is the second gene of a sporulation operon, which altogether
      contains three open reading frames. The ORF preceding spoIV encodes a putative
      polypeptide with 94 amino acids; the 3rd ORF of the operon has 972 bp
      corresponding to 324 amino acids. The operon is flanked on both sides by
      palindromic sequences, probably representing Rho-independent terminators. A
      primer extension analysis revealed that mRNA synthesis starts immediately
      downstream of a promoter, which is similar to the consensus sequence of Bacillus
      subtilis sigma(E) dependent promoters. Both the -35 and the -10 region are within
      the terminator region of the preceding operon. Gene knockout experiments and
      reporter gene assays with a newly developed system based on the heterologous
      Paenibacillus macerans glucanase gene (bgl) confirmed sigma(E)-dependent
      transcription. Two open reading frames of a further upstream operon were also
      identified. Northern analysis revealed that transcription of these ORFs comes
      about in late sporulation phases. The genetic organization of the spoIV
      comprising operon and adjacent loci clearly resembles that of the B. subtilis
      yqfa-phoH gene cluster. Thus our findings are of general significance for
      endospore-forming bacteria.

PMID- 12501412
TI  - Glucoamylase from Thermoanaerobacterium thermosaccharolyticum: Sequence studies
      and analysis of the macromolecular architecture of the enzyme.
AB  - A chromosomal DNA fragment with a length of 2,025 bp, carrying the structural
      gene coding for glucoamylase in Thermoanaerobacterium thermosaccharolyticum, was
      cloned and sequenced. It coded for 695 amino acids, representing a polypeptide
      with a predicted molecular mass of 77.5 kDa. The deduced amino acid sequence
      exhibited high homologies with the glucoamylase sequence of another bacterial
      glucoamylase (Clostridium sp. G0005) and with fungal glucoamylases. The catalytic
      domain (amino acids 271 to 695) of the T. thermosaccharolyticum enzyme shared a
      high degree of similarity (five conserved regions) with the catalytic domain of
      Aspergillus awamori glucoamylase. By comparing the secondary structure of the
      sequence of the catalytic domain of the T. thermosaccharolyticum enzyme with that
      of glucoamylase from A. awamori, and on the basis of X-ray crystallographic data
      available for the A. awamori enzyme, it turned out that, most probably, both
      enzymes have a catalytic domain organized into an "(alpha/alpha)(6)-barrel" and
      an overall size and shape that is very similar. These findings confirm and extend
      our working model for the macromolecular architecture of the T.
      thermosaccharolyticum glucoamylase obtained, in earlier experiments, by electron
      microscopy of negatively stained isolated enzyme molecules. Antibodies for an
      enzyme-specific peptide located near the active site were successfully applied
      for inhibition studies of enzyme activity and for electron microscopic epitope
      mapping. A study comparing the site of attachment of this kind of antibody to the
      T. thermosaccharolyticum glucoamylase molecule with the expected attachment site
      as deduced from the A. awamori enzyme structure confirmed the close similarity of
      both glucoamylases regarding the macromolecular architecture of that part of the
      enzyme carrying the catalytic center, though helices H9, H10, and H11 in
      peripheral parts of the A. awamori enzyme are missing in the T.
      thermosaccharolyticum enzyme.

PMID- 12501413
TI  - Some characteristics of ammonia fungi 1. In relation to their ligninolytic enzyme
      activities.
AB  - Twenty-six species of ammonia fungi comprising 71 strains were screened for
      ligninolytic activity using agar plate tests. The tests comprised a wood powder
      plate test, the Bavendamm reactions, and a Remazol Brilliant blue R (RBBR)
      decolorization test. The wood powder plate test detected phenol oxidases of
      Coprinus spp., whereas this method obviously detected no activities from
      facultative mycorrhizal fungi, such as Hebeloma radicosoides and ectomycorrhiza:
      H. spoliatum and H. vinosophyllum. With quantitative assays of ligninolytic
      activity, Coprinus phlyctidosporus, C. echinosporus, Lyophyllum tylicolor,
      Lepista nuda, L. tarda, Calocybe leucocephala, and Crucispora rhombisperma, which
      grow on oak-leaf litter, the major phenol-oxidizing enzyme was a laccase. The
      concentration of urea affected laccase activity; however, urea was not the
      obligate nitrogen source for the laccase production.

PMID- 12501414
TI  - Breeding of flocculent industrial alcohol yeast strains by self-cloning of the
      flocculation gene FLO1 and repeated-batch fermentation by transformants.
AB  - A nonflocculent industrial polyploid yeast strain, Saccharomyces cerevisiae 396-9
      6V, was converted to a flocculent one by introducing a functional FLO1 gene at
      the URA3 locus. The flocculent strain FSC27 obtained was a so-called self-cloned
      strain, having no bacterial DNA. FSC27 cells could be easily recovered for reuse
      from fermentation mash without any physical energy. The strain produced a
      concentration of alcohol as high as 396-9-6V, although the fermentation rate of
      FSC27 was slightly lower than that of 396-9-6V. When uracil was added to the
      medium or when URA3 was reintroduced into FSC27 (named FSCU-L18), the
      fermentation rate and the growth rate increased, and the ethanol concentration
      produced was higher than that produced by the parent strain. The stable
      flocculation and high ethanol productivity were observed by using FSCU-L18 during
      10 cycles of repeated-batch fermentation test.

PMID- 12501415
TI  - Detection of multiple insertions of group I introns in the nuclear small subunit
      ribosomal RNA gene from the ustilaginomycete Graphiola phoenicis parasitic on
      palm.

PMID- 12501416
TI  - A plasmid pRH45 of Lactobacillus brevis confers hop resistance.

PMID- 12501417
TI  - A Class II fructose-1,6-bisphosphate aldolase from a halophilic archaebacterium
      Haloferax mediterranei.
AB  - Fructose-1,6-bisphosphate (FBP) aldolase (EC 4.1.2.13) was purified 97-fold from
      a halophilic archaebacterium Haloferax mediterranei, with a specific activity of
      2.8. The enzyme was characterized as a Class II aldolase on the basis of its
      inhibition by EDTA and other metal chelators. The enzyme had a specific
      requirement for divalent metal Fe(2+) for activity. Sulfhydryl compounds enhanced
      aldolase activity.

PMID- 12501418
TI  - Exposure to low dose of gamma radiation enhances the excision repair in
      Saccharomyces cerevisiae.
AB  - The effect of low doses of ionizing and nonionizing radiation on the radiation
      response of yeast Saccharomyces cerevisiae toward ionizing and nonionizing
      radiation was studied. The wild-type strain D273-10B on exposure to 54 Gy gamma
      radiation (resulting in about 10% cell killing) showed enhanced resistance to
      subsequent exposure to UV radiation. This induced UV resistance increased with
      the incubation time between the initial gamma radiation stress and the UV
      irradiation. Exposure to low doses of UV light on the other hand showed no change
      in gamma or UV radiation response of this strain. The strains carrying a mutation
      at rad52 behaved in a way similar to the wild type, but with slightly reduced
      induced response. In contrast to this, the rad3 mutants, defective in excision
      repair, showed no induced UV resistance. Removal of UV-induced pyrimidine dimers
      in wild-type yeast DNA after UV irradiation was examined by analyzing the sites
      recognized by UV endonuclease from Micrococcus luteus. The samples that were
      exposed to low doses of gamma radiation before UV irradiation were able to repair
      the pyrimidine dimers more efficiently than the samples in which low gamma
      irradiation was omitted. The nature of enhanced repair was studied by scoring the
      frequency of induced gene conversion and reverse mutation at trp and ilv loci
      respectively in strain D7, which showed similar enhanced UV resistance induced by
      low-dose gamma irradiation. The induced repair was found to be essentially error
      free. These results suggest that irradiation of strain D273-10B with low doses of
      gamma radiation enhances its capability for excision repair of UV-induced
      pyrimidine dimers.

PMID- 12501419
TI  - Phylogeny of Bipolaris inferred from nucleotide sequences of Brn1, a reductase
      gene involved in melanin biosynthesis.
AB  - The Brn1 reductase melanin biosynthesis gene in the fungal genus Bipolaris was
      sequenced in 74 strains of 22 species. The Brn1 region was highly conserved among
      the species examined at the nucleotide and the amino acid levels. To elucidate
      the phylogenetic relationships among Bipolaris species, trees were inferred from
      nucleotide sequences of this region. Species in these trees formed exclusive
      clusters clearly separated from one another, except for B. panici-miliacei and B.
      setariae, and B. victoriae and B. zeicola. When unidentified strains were added
      to this tree, they fell within known species or formed independent clusters.
      These data indicated that the Brn1 gene region was suitable for species-level
      systematics within the genus. The results also suggest that Bipolaris consists of
      two or more clades that may reflect teleomorphic connections.

PMID- 12501420
TI  - Generation and properties of a luminescent insect pathogen Xenorhabdus
      nematophilus (Enterobacteriaceae).
AB  - Studies on the interaction of the insect pathogenic bacterium, Xenorhabdus
      nematophilus (Enterobacteriaceae), with its nematode and insect hosts would be
      greatly assisted if a luminescent phenotype were generated that would allow the
      detection of viable bacteria in vivo without the necessity for disruption of the
      cellular interactions. The plasmid, pMGM221, containing the luminescence gene
      (luxCDABE) of Vibrio harveyi was introduced into different strains (DD136 and
      19061) and phases (one and two) of X. nematophilus by triparental mating. For
      reproducible and efficient conjugation, it was necessary to use older cultures
      (96-160 h) in the stationary phase of X. nematophilus for mating with relatively
      small differences (<2-fold) in transconjugant yield for the different strains and
      phases of X. nematophilus. All transconjugants emitted high levels of light with
      optimum bioluminescence at 27 degrees C in Luria broth at pH 8.0 containing 20
      g/L NaCl; pH, osmolarity, and temperature conditions were similar to those
      encountered by the bacteria in the hemolymph of the larvae of Galleria
      mellonella. Plasmids were detected in the transconjugants after 6 months of
      subculturing the bacteria without antibiotic selection. Aside from light
      emission, luminescent transconjugants had the same physiological properties as
      the nonluminescent parental strains, including identical rates of growth,
      production of exoenzymes, removal from and subsequent emergence into the insect's
      hemolymph, bacterial-induced hemocyte damage, suppression of prophenoloxidase
      activation, and the ability to kill G. mellonella larvae. Light-emitting larvae
      could readily be detected by eye in a dark room, and all bacteria reisolated from
      dead larvae were luminescent. These properties validate the use of luminescent X.
      nematophilus not only as a means of following bacterial host interactions, but
      also as a potential agent to follow the infection and death of the insect
      population.

PMID- 12501421
TI  - Purification and characterization of beta-1,3-xylanase from a marine bacterium,
      Alcaligenes sp. XY-234.
AB  - A beta-1,3-xylanase-producing bacterium, Alcaligenes sp. XY-234, was isolated
      from the marine environment. The organism produced endo-1,3-beta-xylanase at a
      high level in the culture fluid. The enzyme was purified 292-fold by ammonium
      sulfate precipitation and several column chromatographies. The final enzyme
      preparation appeared to be homogeneous on disc gel electrophoresis and SDS-PAGE
      with a molecular mass of 59 kDa, and the pI was 4.0. The enzyme hydrolyzed beta
      1,3-xylan and larger xylooligosaccharides than xylobiose to give several
      xylooligosaccharides, but it could not hydrolyze xylobiose, p-nitrophenyl-beta-D
      xyloside, and beta-1,4-xylan. The Km of the enzyme was 4.0 mg/ml. Optimal pH and
      temperature were 7.5 and 40 degrees C, respectively. It was stable from pH 6.0 to
      10 and at a temperature of less than 40 degrees C. The enzyme was strongly
      inhibited by 1 mM HgCl(2)., AlCl(3), CuCl(2), FeCl(3), HgCl(2), Pb(CH(3)COO) (2),
      and N-bromosuccinimide.

PMID- 12501422
TI  - Region specificity of chromosome III on gene expression in the yeast
      Saccharomyces cerevisiae.
AB  - A single copy of a reporter gene cassette, such as PGKP-lacZ-LEU2 (promoter
      reporter-marker gene) cassette, was inserted into one of 32 positions along
      chromosome III in Saccharomyces cerevisiae with an interval of approximately 10
      kb. The amounts of translational gene product (beta-galactosidase) synthesized by
      the cassette-transformed cells were then determined. The region specificity in
      chromosome III could be demonstrated in gene expression: two higher-expressed
      regions (hot regions), 133 and 199 (MAT) regions, and seven lower-expressed
      regions (cold regions). For the steady and high production of polypeptide,
      foreign gene products, by yeast, we would like to state that we hope for an
      insertion of the artificially prepared gene cassette [(promoter)-(foreign gene)
      (marker gene) ] into a hot region, such as 199 (MAT) region of chromosome III.

PMID- 12501423
TI  - Ultrasonic enhancement of antibiotic action on several species of bacteria.
AB  - The effect of the antibiotics gentamicin, streptomycin, kanamycin, tetracycline,
      and ampicillin on planktonic cultures of Enterobacter aerogenes, Serratia
      marcescens, Salmonella derby, Streptococcus mitis, and Staphylococcus epidermidis
      with and without an application of 70 kHz ultrasound was studied. The ultrasound
      was applied at levels that had no inhibitory effect on planktonic cultures of
      bacteria. Measurements of viability at, above, and below the minimum inhibitory
      concentration of the above antibiotics on the planktonic cultures of these
      bacteria showed that a simultaneous application of 70 kHz ultrasound and
      antibiotic significantly increased the effectiveness of selected antibiotics.
      Bacterial viability was reduced several orders of magnitude when harmless levels
      of ultrasound were combined with some antibiotics, especially the
      aminoglycosides. Similar synergistic effects of combined ultrasound and
      antibiotic treatment were seen in both Gram-positive and Gram-negative bacteria
      with several classes of antibiotics. These results may have application in the
      treatment of bacterial infections normally resistant to some antibiotics.

PMID- 12501424
TI  - Moritella japonica sp. nov., a novel barophilic bacterium isolated from a Japan
      Trench sediment.
AB  - Strain DSK1 is a novel moderately barophilic bacterium isolated from the Japan
      Trench at a depth of 6,356 m. Phylogenetic analysis based on 16S ribosomal DNA
      sequences showed that strain DSK1 represents a separate lineage with the
      Shewanella barophiles branch and is closely related to Moritella marina.
      Comparisons of the temperature and pressure range for growth and some biochemical
      characteristics indicate that strain DSK1 differs from M. marina and Shewanella
      barophilic species. Furthermore, strain DSK1 displays a low level of DNA
      similarity to the Moritella and Shewanella type strains; however this isolate
      characteristically produces DHA (22:6) as a membrane fatty acids, and the fatty
      acid profile of this strain is similar to that of M. marina. Because of these
      differences, strain DSK1 appears to represent a novel deep-sea Moritella species.
      The name Moritella japonica is proposed. The type strain is JCM 10249.

PMID- 12501425
TI  - Interaction between methanogenic and sulfate-reducing microorganisms during
      dechlorination of a high concentration of tetrachloroethylene.
AB  - A methanogenic and sulfate-reducing consortium, which was enriched on medium
      containing tetrachloroethylene (PCE), had the ability to dechlorinate high
      concentrations of PCE. Dehalogenation was due to the direct activity of
      methanogens. However, interactions between methanogenic and sulfate-reducing
      bacteria involved modification of the dechlorination process according to culture
      conditions. In the absence of sulfate, the relative percentage of electrons used
      in PCE dehalogenation increased after an addition of lactate in batch conditions.
      The sulfate reducers would produce further reductant from lactate catabolism.
      This reductant might be used by methanogenic bacteria in PCE dechlorination. A
      mutualistic interaction was observed in the absence of sulfate. However in the
      presence of sulfate, methanogenesis and dechlorination decreased because of
      interspecific competition, probably between the H(2)-oxydizing methanogenic and
      sulfate-reducing bacteria in batch conditions. In the semicontinuous fixed-bed
      reactor, the presence of sulfate did not affect dechlorination and
      methanogenesis. The sulfate-reducing bacteria may not be competitors of H(2)
      consuming methanogens in the reactor because of the existence of microbial
      biofilm. The presence of the fixed film may be an advantage for bioremediation
      and industrial treatment of effluent charged in sulfate and PCE. This is the
      first report on the microbial ecology of a methanogenic and sulfate-reducing PCE
      enrichment consortium.

PMID- 12501426
TI  - Overproduction of alpha-glucosidase in Aspergillus niger transformed with the
      cloned gene aglA.
AB  - We have transformed an industrial strain, Aspergillus niger GN-3, with the alpha
      glucosidase gene (aglA) from the same strain. Southern hybridization analysis
      revealed that transformants had multiple copies of the cloned DNA inserted into
      the host genome. An 11-fold improvement of enzyme production was achieved by
      transformation with a DNA fragment composed of 1.11 kb of the 5' noncoding
      region, 3.12 kb of the coding region containing three introns, and 1.2 kb of the
      3' noncoding region. It was found that the 3' noncoding region (1.2 kb) was
      preferable for maximum production of the enzyme in the transformant.

PMID- 12501427
TI  - Physiological and biochemical aspects of the acid survival of Listeria
      monocytogenes.
AB  - The physiological aspects of the response to acidic conditions and the correlated
      protein synthesis were studied by using Listeria monocytogenes grown in a
      chemically defined synthetic medium. This growth was greatly affected by pH of
      the medium. It decreased when pH declined and was arrested at pH 4. When pH went
      under 4, the bacteria began to die. If the bacteria had been adapted to an
      intermediary sublethal pH before imposition of lethal pH stress, they would have
      resisted better lethal pH. A prolonged treatment at intermediary pH, however,
      rendered the bacteria more sensitive to subsequent lethal pH. Organic volatile
      acids exerted a more deleterious effect on L. monocytogenes than inorganic acids
      at the same stressing pH. The acquired acid tolerance was conserved after several
      weeks of storage of the adapted bacteria at 4 degrees C. Acid stress and acid
      adaptation (tolerance) affected the synthesis patterns of bacterial proteins:
      Many proteins were repressed and several others increased in expression level.
      These acid-induced proteins were separated by two-dimensional (2D-)
      electrophoresis and analyzed by a computer-aided 2D-gel analysis system. The
      results obtained suggested that acid tolerance and acid stress responses require
      the synthesis of a certain number of shared proteins and that additional acid
      induced proteins are needed when the bacteria must face more severe acidic pH.

PMID- 12501428
TI  - Lactic acid bacteria found in fermented fish in Thailand.
AB  - Forty-seven strains of homofermentative rod-shaped and 5 heterofermentative
      sphere-shaped lactic acid bacteria were isolated from 4 kinds of fermented fish
      (pla-ra, pla-chom, kung-chom, and hoi-dong) in Thailand. These bacteria were
      separated into four groups by phenotypic and chemotaxonomic characteristics,
      including fluorometric DNA-DNA hybridization. Five strains (Group I) contained
      meso-diaminopimelic acid in the cell wall. Four strains were identified as
      Lactobacillus pentosus, and one strain was L. plantarum. Tested strains of this
      group produced DL-lactic acid. The rest of the rod-shaped bacteria, 23 strains
      (Group II) and 19 strains (Group III), lacked meso-diaminopimelic acid in the
      cell wall and were identified as L. farciminis and Lactobacillus species,
      respectively. The tested strains of these groups produced L-lactic acid. The
      amount of cellular fatty acids of C16:0 and C18:1, and the DNA base compositions
      were significant for differentiating the strains in Groups II and III. Five
      strains of cocci in chains (Group IV) produced gas from glucose. The tested
      strains of this group produced d-lactic acid. They were identified as a
      Leuconostoc species. The distribution of these bacteria in fermented fish in
      Thailand is discussed.

PMID- 12501429
TI  - Reclassification of marine Agrobacterium species: Proposals of Stappia stellulata
      gen. nov., comb. nov., Stappia aggregata sp. nov., nom. rev., Ruegeria atlantica
      gen. nov., comb. nov., Ruegeria gelatinovora comb. nov., Ruegeria algicola comb.
      nov., and Ahrensia kieliense gen. nov., sp. nov., nom. rev. 
AB  - The bootstrapped 16S rDNA sequence-based neighbor-joining phylogeny has suggested
      that the marine species of the genus Agrobacterium have no relation to the
      terrestrial Agrobacterium species. Agrobacterium atlanticum IAM 14463(T) (a
      superscript (T)=type strain), Agrobacterium ferrugineum IAM 12616(T),
      Agrobacterium gelatinovorum IAM 12617(T), Agrobacterium meteori IAM 14464(T),
      Agrobacterium stellulatum IAM 12621(T) and IAM 12614, and the invalidly published
      marine species "Agrobacterium kieliense" IAM 12618 occupy an independent position
      in the a-subclass of the Proteobacteria. Based on 16S rDNA sequencing and on
      chemotaxonomic, morphological, and physiological studies, we propose the transfer
      of A. atlanticum, A. gelatinovorum, and Roseobacter algicola to the genus
      Ruegeria gen. nov. as Ruegeria atlantica comb. nov., Ruegeria gelatinovora comb.
      nov., and Ruegeria algicola comb. nov., respectively; of strains of A.
      stellulatum to the genus Stappia gen. nov. as Stappia stellulata comb. nov. and
      Stappia aggregata sp. nov., nom. rev., respectively; and of "A. kieliense" to the
      genus Ahrensia gen. nov. as Ahrensia kieliense sp. nov., nom. rev. Agrobacterium
      meteori is assigned to be a synonym of A. atlanticum.

PMID- 12501430
TI  - A comparison of raw starch-digesting glucoamylase production in liquid and solid
      cultures of Rhizopus strains.
AB  - Maximum growth for Rhizopus sp. A-11 was obtained at a zinc ion concentration of
      0.7 ppm in a liquid medium. Glucoamylase (GA, EC 3.2.1.3) production in Rhizopus
      sp. A-11 was maximized at 710 U/ml, at the presence of 75 ppm for calcium and 0.7
      ppm of zinc ions in liquid medium. Zinc ion is known as an essential biometal for
      Rhizopus growth; however, growth was inhibited by the zinc ion concentration, not
      maximized. Although calcium ion was not necessary to Rhizopus growth, GA
      production using Rhizopus sp. A-11 was markedly stimulated by calcium ion
      concentration over 75 ppm in the liquid medium. The GA productivity of the
      present liquid culture was about 4.4 times higher than that of the solid state
      culture, based on the unit starch amount in the liquid and solid media carbon
      source. The characteristics of the GA produced by the Rhizopus sp. A-11 liquid
      culture were interesting; that is, almost all the GA produced was classified as
      raw starch-digesting GA (GA-I). Secreted protein in the culture liquid after 30 h
      was nearly GA, and had a limited amount of impure protein. As a result, it was
      found that using a Rhizopus culture in a specified metal-ion regulated medium was
      an effective method for producing GA. Thus the present culture method was renamed
      the "metal-ion-regulated liquid culture method".

PMID- 12501431
TI  - Molecular analysis and characterization of the Cochliobolus heterostrophus beta
      tubulin gene and its possible role in conferring resistance to benomyl.
AB  - Cochliobolus heterostrophus Tub1 described here is the first beta-tubulin gene
      characterized from a naturally occurring benomyl-resistant ascomycete plant
      pathogen. The gene encodes a protein of 447 amino acids. The coding region of
      Tub1 is interrupted by three introns, of 116, 55, and 56 nt, situated after
      codons 4, 12, and 53, respectively. As a result of the preference for pyrimidines
      in the third position of the codons when a choice exists between purines and
      pyrimidines, codon usage in the Tub1 gene is biased. Tub1 shows high homology
      with beta-tubulin genes of other ascomycete species. However, Tub1 is exceptional
      in having Tyr(167), compared with Phe(167), possessed by beta-tubulin genes of
      other ascomycetes sequenced thus far. The Tyr(167) residue has been associated
      with benomyl resistance in other organisms. In contrast, all other benomyl
      implicated residues of Tub1 correspond to sensitivity. Based on these results, we
      suggest that benomyl resistance in the fungus probably is attributed to Tyr(167).

PMID- 12501432
TI  - Evolutionary relationships among Aspergillus oryzae and related species based on
      the sequences of 18S rRNA genes and internal transcribed spacers.

PMID- 12501433
TI  - PCR-based method for isolation of the flagellin genes from Pseudomonas species.

PMID- 12501434
TI  - Application of the hypervariable region of the 16S rDNA sequence as an index for
      the rapid identification of species in the genus Alicyclobacillus.
AB  - A comparison of the 16S rRNA gene (rDNA) sequences of seven type strains
      belonging to different Alicyclobacillus species (i.e., five validated species,
      one proposed species and one genomic species) suggested that the 5' end
      hypervariable region (259-273 bases in length) of 16S rDNA was specific for the
      respective type strains. Further phylogenetic analysis based on DNA sequences of
      the hypervariable region using 24 Alicyclobacillus strains revealed that the
      strains could be categorized into five species and the A. acidocaldarius
      Alicyclobacillus genomic species 1 group. The hypervariable region was highly
      conserved among the five species: A. acidiphilus, A. acidoterrestris, A.
      cycloheptanicus, A. herbarius, and A. hesperidum. The strains in the A.
      acidocaldarius-Alicyclobacillus genomic species 1 group were subdivided into two
      clusters (Clusters I and II) based on DNA sequences in the hypervariable region.
      On the basis of phenotypic characteristics, chemotaxonomic and phylogenetic
      analyses, and DNA-DNA hybridization data, strains in Cluster I were grouped as
      Alicyclobacillus genomic species 1 and strains in Cluster II were re-identified
      as A. acidocaldarius, thereby demonstrating that the hypervariable regions were
      also highly conserved within these two species. These results suggest that as is
      the case with Bacillus, the hypervariable region is significantly species
      specific in the genus Alicyclobacillus to distinguish Alicyclobacillus species by
      DNA sequence comparison of the hypervariable region.

PMID- 12501435
TI  - A preliminary report of phylogenetic diversity of bacterial strains isolated from
      marine creatures.
AB  - Bacterial diversity among marine creatures, especially molluscs, as a source for
      searching out novel lineages of bacteria, was studied. Marine creatures were
      collected at the coasts of the Kanto area in Japan. A total of 116 strains of
      bacteria were isolated from the intestines of 19 species of marine creatures
      includings molluscs, pisces and protochordata. Partial sequencing of 16S rDNA
      revealed that most of the isolates belonged to the gamma subclass of the
      Proteobacteria and Cytophaga-Flavobacterium-Bacteroides group. The BLAST searches
      revealed that the complete 16S rDNA sequence of 17 strains out of 116 isolates
      showed less than 94% similarity with 16S rDNA sequences deposited in the
      database. Four strains out of the 17 isolates belonged to the Rhodobacter group,
      8 strains to the Alteromonas group, and the remaining 5 strains to the Cytophaga
      Flavobacterium-Bacteroides group. Phylogenetic positions of 6 strains belonging
      to the Alteromonas group, which were isolated from different marine creatures,
      were close to each other, and represented a novel 16S rDNA lineage within the
      gamma subclass of Proteobacteria. Therefore, it may be inferred that these 6
      strains belong to a new genus of Proteobacteria. Phylogenetic positions of the
      other strains are also independent from neighboring taxa, and they were suggested
      to respectively form a novel lineage. From these results, it is clear that the
      biodiversity of bacteria in marine creatures is much wider than was previously
      thought, and unknown microbiological resources are buried in these organisms.

PMID- 12501436
TI  - Isolation and clonal pre-selection of enological Saccharomyces.
AB  - The aim of the present study was to perform a fast pre-selection from a great
      number of wine yeasts using a simple phenotypic-based methodology that allows
      many different strains to be simultaneously tested. A total of 150 elliptic
      yeasts, isolated from must and wine from black grapes of a distinctive Italian
      variety, were studied. Yeasts were identified to genus level by assessing their
      ability to ferment glucose and their production of spores on acetate agar. The
      Saccharomyces strains were seeded on BiGGY agar to determine their H(2)S
      production, on calcium carbonate agar to test their acetic acid production, and
      on grape-skin agar and on grape-seed agar to assess their interaction with
      phenolic compounds. The Saccharomyces strains were also examined for fermentative
      vigor after 2 d or 7 d both with and without the addition of 100 mg L(-1) of
      SO(2) in must at 20 degrees brix and pH 3.20. At the end of fermentation, the
      wines produced by the 18 best yeasts were analyzed and the strains were studied
      for additional biochemical and technological characteristics. The resistance of
      the strains to simultaneous acid-stress and osmotic-stress was studied carrying
      out in duplicate winemaking tests in must at 30 degrees brix and pH 2.60. A
      remarkable heterogeneity among the 150 autochthonous yeasts studied was
      demonstrated. The phenotypical biodiversity is particularly interesting for
      several technological characteristics useful in winemaking, such as fermentation
      vigor, acetic acid production and malic acid content of the wines. The vast
      majority of the elliptic wine yeasts isolated did not show suitable
      characteristics, so only 18 strains, 12% of the total, remained for the final
      tests. Many of the strains that had passed the preliminary screenings revealed
      some defects when they were studied for fermentation performance, both in
      standard winemaking and under stressors. Two strains exhibited particularly
      interesting performances: one strain for winemaking of normal musts and the other
      for winemaking of musts from dried grapes or under stressful conditions.

PMID- 12501437
TI  - Paraliobacillus ryukyuensis gen. nov., sp. nov., a new Gram-positive, slightly
      halophilic, extremely halotolerant, facultative anaerobe isolated from a
      decomposing marine alga.
AB  - A slightly halophilic, extremely halotolerant, alkaliphilic, and facultatively
      anaerobic rod bacterium was isolated from a decomposing marine alga collected in
      Okinawa, Japan. The isolate, designated O15-7(T), was Gram-positive, endospore
      forming, catalase-positive, menaquinone-7-possessing bacterium that is motile by
      peritrichous flagella. The isolate was an inhabitant of marine environments; the
      optimum NaCl concentration for growth was 0.75-3.0% (w/v) with a range of 0
      22.0%, and the optimum pH was 7.0-8.5 with a range of 5.5-9.5. Catalase was
      produced in aerobic cultivation but not in anaerobic cultivation. Carbohydrate,
      sugar alcohol or a related carbon compound was required for growth. In aerobic
      cultivation, the isolate produced pyruvate, acetate and CO(2) from glucose, and
      in anaerobic cultivation, it produced lactate, formate, acetate and ethanol with
      a molar ratio of approximately 2 : 1 : 1 for the last three products. No gas was
      produced anaerobically. Lactate yield per consumed glucose was markedly affected
      by the pH of the fermentation medium: 51% at pH 6.5 and 8% at pH 9.0. The cell
      wall peptidoglycan contained meso-diaminopimelic acid. Phylogenetically, the
      isolate occupied an independent lineage within the group composed of the
      halophilic/halotolerant/alkaliphilic and/or alkalitolerant species in Bacillus
      rRNA group 1 with the highest 16S rRNA gene sequence similarity of 95.2% to the
      genus Gracilibacillus. For this isolate, Paraliobacillus ryukyuensis gen. nov.,
      sp. nov. was proposed. The type strain, O15-7(T) (G+C535.6 mol%), has been
      deposited in the DSMZ, IAM, NBRC, and NRIC (DSM 15140(T)=IAM 15001(T)=NBRC
      10001(T)=NRIC 0520(T)).

PMID- 12501438
TI  - Evaluation of the hypervariable region in the 16S rDNA sequence as an index for
      rapid species identification in the genus Paenibacillus.

PMID- 12501439
TI  - PCR cloning and heterologous expression of cDNA encoding a peptidyl-Lys
      metalloendopeptidase precursor of Grifola frondosa.

PMID- 12501440
TI  - A basidiomycetous anamorphic yeast, Trichosporon terricola sp. nov., isolated
      from soil.

PMID- 12501441
TI  - Less than ready.

PMID- 12501442
TI  - Gaps in the map.

PMID- 12501443
TI  - Health on the streets. Interview by Dina Leifer.

PMID- 12501444
TI  - Bye bye baby....

PMID- 12501445
TI  - Regulating sexuality.

PMID- 12501446
TI  - Educated eating.

PMID- 12501447
TI  - Nurse-directed services in genitourinary medicine.
AB  - BACKGROUND: Experienced nurses in a genitourinary medicine (GUM) department were
      given further training to enable them to take a medical and presenting sexual
      history on a patient's first visit to the department. The nurses were also
      trained to examine and treat male patients, having previously only examined
      female patients at follow-up clinics. Protocols on the examination of new
      patients and patient group directions were devised to permit nurses to prescribe
      certain antibiotics for patients. CONCLUSION: The audit examined the care
      provided by nurses for a sample of 300 patients in a GUM department. The results
      showed that a variety of conditions were successfully diagnosed and treated by
      nurses, and that patients, nurses and medical staff were satisfied with the nurse
      directed service.

PMID- 12501448
TI  - Essence of Care: making a difference.
AB  - Essence of Care (DoH 2001) developed from a commitment to explore the benefits of
      benchmarking in improving the quality of the fundamental and essential aspects of
      care (DoH 1999). The NHS Plan (DoH 2000) reinforced the importance of getting the
      basics right and improving the patient's experience. During the 18 months since
      the publication of the Essence of Care clinical benchmarks (DoH 2001), it has
      moved steadily from political rhetoric to clinical reality in the Central South
      Regional Group (CSRG). This article describes the role of the CSRG steering
      committee in co-ordinating the implementation of Essence of Care. This involved:
      Education about the benchmarking process. Support for implementation of the
      benchmarks. Evaluation of the process to date. Direction for future developments.
      The CSRG steering committee comprises representation from many of the trusts in
      the CSRG (Table 1), as well as the University of Southampton and New Forest PCT.

PMID- 12501449
TI  - Paediatric resuscitation: advanced life support.
AB  - The author describes the paediatric advanced life support algorithm and discusses
      specific aspects of paediatric resuscitation.

PMID- 12501450
TI  - [Kislovodsk Central Military Sanatorium--one of the leading health resorts of the
      Northern Caucasus].

PMID- 12501451
TI  - Preparing occupational therapists for practice today and into the future.

PMID- 12501452
TI  - Impact of wheeled seated mobility devices on adult users' and their caregivers'
      occupational performance: a critical literature review.
AB  - The prescription of wheeled seated mobility devices for clients with mobility
      impairment is a growing area in occupational therapy practice. The goal is to
      enhance client participation in occupation through technical intervention. This
      critical review examines the body of knowledge concerning the impact and
      effectiveness of the provision of wheeled seated mobility on the occupational
      performance of wheelchair users and their caregivers. The scope and gaps in the
      literature are defined to identify areas for future research. While the focus is
      on the methodological issues of the research reports, the relevance of findings
      to occupational therapy practice will also be reviewed. The results of the 46
      studies in this review indicate that the majority of research conducted thus far
      have methodological limitations, which limits the extent to which this body of
      research can be drawn upon to provide evidence for the effectiveness of wheeled
      mobility systems. While most of the studies reviewed addressed constructs of
      relevance to occupational therapy practice, there was an emphasis on performance
      components and inadequate attention to engagement in occupations. This review is
      an important first step in building the ability of occupational therapists to
      demonstrate effectiveness in wheeled seating interventions.

PMID- 12501453
TI  - Unawareness and/or denial of disability: implications for occupational therapy
      intervention.
AB  - Occupational therapy focus on client-centred, occupational performance
      intervention may become complicated by the phenomena of self-awareness. The
      problem of awareness deficits in clients with neurological disorders may be
      attributed to neurological impairment of self-awareness and/or psychological
      denial of disability. These phenomena present themselves more commonly in
      combination than dichotomously and have implications for treatment outcomes.
      Individuals with impaired self-awareness or denial face difficulties with
      motivation and participation in therapy, and the adoption of compensatory
      strategies, which ultimately impacts on rehabilitation outcome. The extent of
      unawareness versus denial can be assessed by observation of a client's behavior
      and this information can be very useful in directing the treatment approach. The
      purpose of this paper is, therefore, to discuss the phenomenon of unawareness
      and/or denial of disability and its importance to successful rehabilitation
      outcomes, current thinking and research conducted in different countries. Also,
      detailed case examples of three clients representing three major populations of
      traumatic brain injury, stroke and schizophrenia who may exhibit unawareness
      and/or denial of disability will be presented, including intervention strategies
      for both phenomena.

PMID- 12501454
TI  - Professional accountability in restructured contexts of occupational therapy
      practice.
AB  - Professional standards for accountability establish essential competencies for
      clinical practices and provide strategies for professional advancement. This
      study examines the perspectives of a sample of occupational therapists on their
      capacity to engage in continuing education, to provide evidence-based practices
      and to have confidence in the effectiveness of available quality assurance
      mechanisms within restructured contexts of occupational therapy practice. The
      analysis of in-depth interviews with participants from program management,
      managed competition and private practice suggested three urgent needs: the
      development of strategies to assist therapists' translation of research evidence
      into clinical practices, research to determine the effectiveness of models of
      professional leadership within the workplace that promote professional
      accountability and alliances to advance policies that eliminate workplace
      barriers to professional accountability.

PMID- 12501455
TI  - [Evaluation of volume and degree of blood loss in trauma of the chest and the
      abdomen].
AB  - A mathematical method based on a complex of capillary blood examinations was
      proposed and tested for detection of volume and degree of blood loss in trauma of
      the chest and the abdomen. This method may be used for optimization of
      intraoperative fluid management. It is very important when bleeding is not only
      into the serous cavities (blood loss is easy to evaluate during surgery) but also
      into the intermuscular and interstitial spaces, and also in internal hemorrhage.

PMID- 12501456
TI  - [Treatment policy for children with gastroesophageal reflux complicated by
      Barrett esophagus].
AB  - Barret's esophagus (BE) is a rare disease in children. It is caused by
      gastroesophageal reflux (GER). From 1996 to 1999 seventy-eighth children with GER
      were treated. Twenty-four-hour pH-metry and manometry of the esophagus,
      scintigraphy and contrast roentgenoscopy of the esophagus were used for diagnosis
      of GER. All the children underwent biopsy of mucosa membrane of distal esophagus.
      Morphologic examinations revealed BE in 16 (20.5%) children. Metaplasia of
      esophageal epithelium by intestinal type (IT) in combination with one by gastric
      type (GT) were revealed in 8 children, metaplasia by gastric type alone
      (epithelium of gastric and fundal parts of the stomach)--in 8 children. Six
      children with IT metaplasia of the esophagus with long strictures underwent
      extirpation of the esophagus with one-stage esophagoplasty. It esophageal
      stenosis is not long or is absent, fundoplication by Nissen (4 children) and drug
      therapy (6 children) are performed. It is concluded that in IT metaplasia of the
      esophagus with long peptic esophageal strictures resistant to bouginage
      extirpation of the esophagus with one-stage coloesophagoplasty is desirable.
      Other methods of treatment do not exclude probability of esophageal
      adenocarcinoma. These children should be followed up with esophageal biopsy each
      6-12 months.

PMID- 12501457
TI  - [Laparoscopic splenectomy in congenital hemolytic anemia in children].
AB  - Experience of 48 laparoscopic splenectomies in children aged from 3 to 14 years
      with congenital hemolytic anemia is analyzed. The main stages of laparoscopic
      splenectomy were the following: isolation of the inferior pole of the spleen,
      transection of the gastro-splenic ligament, transection of the splenic vascular
      trunk (with endostapler or intracorporeal ligature), dissection of the splenic
      ligaments, removal of the organ (with endoscopic sac or morcellator). One-stage
      cholecystectomy for cholelithiasis was performed in 11 patients. Time of surgery
      was 110-115 minutes, on the average. One-stage cholecystectomy prolonged surgery
      by 30-40 minutes. There were no intraoperative and postoperative complications.
      Conversion to open surgery was necessary in 2 cases because of endostapler
      failure. Patients were discharged on the 5-8th day after surgery. Physical
      activity restored completely 10-14 days after surgery. There were no lethal
      outcomes. Excellent cosmetic results were achieved in all the patients.
      Laparoscopic splenectomy in congenital hemolytic anemia is safe, sparing and
      effective endoscopic surgery in childhood.

PMID- 12501458
TI  - [The terms of esophagoplasty in children with esophageal atresia].
AB  - From 1995 to 2000 twenty-seven coloesophagoplasties were performed in children
      with esophageal atresia aged from 3 months to 2 years. Patients were divided into
      2 groups depending on their age. Group 1 consisted of 13 children aged from 3 to
      6 months (mean 5.5 months), group 2-14 children aged from 6 to 24 months (mean 13
      months). Course of postoperative period and postoperative complications were the
      criteria of treatment results. All the parameters were similar in both groups.
      Postoperative diarrhea was seen more often in group 1. It is concluded that
      esophagoplasty in children with atresia must be performed as early as possible.

PMID- 12501459
TI  - [Surgical treatment of duodenal ulcer in elderly and aged patients].
AB  - Choice of treatment of duodenal ulcer in elderly and aged patients is discussed.
      Literature demonstrate high risk of recurrences even in adequate systemic drug
      treatment. In patients of this age group early organo-saving operations must be
      performed before development of complications. Results of selective proximal
      vagotomy in 62 patients aged from 60 to 82 years confirm efficacy and minimal
      risk of this surgery.

PMID- 12501460
TI  - [A comparative assessment of modern suture materials in stomach resection].
AB  - Results of stomach resection by Bilrot-II in 30 experimental animals and 369
      patients with gastric and duodenal ulcers were analyzed. Gastroenteroanastomoses
      were created with various sutures: capron, polysorb, titanium clips.
      Pneumopression, bacteriologic and morphologic examinations of anastomosis,
      fibroesophagogastroduodeno- and intestinoscopy, peripheral computed
      electrogastroenterography were used. It was revealed that mechanical suture with
      titanium clips was the best. Polysorb thread is inferior in tissue reaction to
      mechanical suture but superior to capron. Use of polysorb reduced rate of
      complications in immediate postoperative period 4 times. Taking into
      consideration high cost of suture devices it is reasonable to introduce polysorb
      in practice of abdominal surgery.

PMID- 12501461
TI  - [Prognosis of ulcer bleeding recurrence].
AB  - The conception of prerecurrence syndrome is suggested. Clinical, endoscopic and
      laboratory characteristics of prerecurrence syndrome are described. Causes of
      ulcer bleeding recurrence were examined: continued ulcer alteration, digestion of
      a thrombus in ulcer, fibrinolysis of a thrombus in an arrosive vessel,
      hyperdynamic regional circulation. Individual surgical policy was developed.
      Urgent surgery is indicated in continued hemorrhage and verified prerecurrence
      syndrome.

PMID- 12501462
TI  - [Laparoscopic diagnosis and treatment of acute pancreatitis].
AB  - Laparoscopy and pancreatoscopy were performed in 2091 (62% of all hospitalized)
      patients with acute pancreatitis. High informative value of laparoscopy and
      pancreatoscopy in diagnosis of different morphologic forms of acute pancreatitis
      is demonstrated. Original fistula for pancreatoscopy was developed. It permits
      one to evaluate visually the dynamics of repair in the pancreas and surrounding
      tissues and to correct treatment policy.

PMID- 12501463
TI  - [Surgical treatment of cholelithiasis in elderly and aged patients].
AB  - Surgical treatment of cholelithiasis in 485 elderly and aged patients operated
      from 1991 to 2000 are analyzed. Patients with acute inflammation in the biliary
      tract underwent surgery after standard conservative therapy during 12-48 hours
      after hospitalization. Methods of completion of surgery on the biliary tract are
      proposed: treatment of the bile cyst bed after cholecystectomy associated with
      lesion of hepatic tissue; methods of external and internal drainage of the major
      bile ducts and drainage of infrahepatic space through loin. Epidural blocking was
      used as the main component of combined anesthesia. These methods of surgical
      treatment in elderly and aged patients reduce number of postoperative
      complications and shorten hospital stay.

PMID- 12501464
TI  - ["Small" tumors of the adrenal glands. Disputable points of a surgical
      technique].
AB  - Experience of 249 surgeries for "small" tumors of the adrenal glands whose (3-4
      cm in size maximum) are analyzed. In 212 patients a small extracavitary approach
      through the bed of rib XI was used, in 12--thoracophrenolumbotomy through the
      tenth intercost. Endoscopic technology of removal of "small" adrenal tumors with
      transperitoneal approach was used in 25 patients. Advantages and shortcomings of
      "open" and endoscopic surgeries are analyzed. It is concluded that non-traumatic
      extracavitary approach with resection of rib XI or endoscopic technology are best
      for removal of "small" adrenal tumors. Small experience of endoscopic
      adrenalectomies doesn't permit to judge definitely about the advantage of this
      surgery compared with small extracavitary approach.

PMID- 12501465
TI  - [Long-term block of thoracic vegetative nerve trunks in combined treatment of
      acute intestinal obstruction].
AB  - Results of treatment of acute intestinal obstruction with long-term block of the
      left thoracic sympathetic trunk, paraaortal and paraesophageal vegetative
      plexuses, vagus and posterior bronchial plexuses are analyzed. Compared with long
      term epidural block this method permits one to reduce 2 times the rate of
      postoperative complications and lethality, to shorten the hospital stay by 5
      days. Long-term block of thoracic vegetative nervous trunks provide manipulations
      out of structures of the spinal column and permits to influence directly both
      parts of the vegetative nervous system.

PMID- 12501466
TI  - [Possibility of combined surgeries in locally advanced rectal cancer].
AB  - Results of treatment of 28 patients with locally advanced rectal cancer are
      analyzed. Abdomino-perineal extirpation of the rectum with colostomy was
      performed in 11 patients, abdomino-anal resection with colo-anal anastomosis--in
      10, Hartmann's operation--in 7. In 18 cases resection of the posterior wall of
      the urinary bladder was performed simultaneously, in 3--resection of the ureter
      with allotransplantation, in 5--supravaginal amputation of the uterus. Eleven
      patients survive one year after surgery. General status evaluated with
      Karnovsky's scale was 80-90% in 5 patients, 60%--in 4, and 40% in 2 patients.
      Seven patients survive three years after surgery. Karnovsky's scale index was 80%
      in 3 patients of them, 60%--in 3, and 30%--in 1 patient. Four patients survive 5
      years with 60% (3 patients) and 40% (1 patient) general status index. It is
      recommended to perform combined surgeries for rectal cancer in invasion of the
      tumor into neighbouring organs. They don't make worse immediate results of
      treatment and relieve patients of complications due to spread of rectal cancer
      into the urinary organs.

PMID- 12501467
TI  - [Reliability of the sterilization of surgical instruments is a key point in
      prevention of surgical infection].
AB  - Occurrence of postoperative purulent-inflammative complications (PPIC), their
      structure and dynamics after improvement of sterilization are studied. For
      epidemiological analysis 65,246 medical histories of operated patients were
      studied, in 404 of them PPIC were revealed. The PPIC rate reduced from 3.05% in
      1981 to 0.49 in 2000 though surgical activity increased 12 times after this
      period. Thus developed measures for improvement of sterilization promoted
      reduction of the PPIC rate.

PMID- 12501468
TI  - [Differentiated surgical policy in destructive pancreatitis].
AB  - A total of 4522 patients with acute pancreatitis (AP), 1142 from them with
      pancreonecrosis (PN), were treated in surgical clinics of Saratov Military
      Medical Institute in 1990-2002. Intervention was made in 381 patients. Is shown,
      that the introduction of modern methods of treatment new operative receptions,
      change of the indications for "open" drainage operations, use of original policy
      surgical classification has allowed to lower a mortality from AP from 12 to
      8.25%, and postoperative lethality from 38.1 up to 19.5%. At the analysis of
      results of work the doubtless positive effect of application Sandostatin fixed at
      treatment.

PMID- 12501469
TI  - [Laparoscopic surgery in abdominal adhesive process].

PMID- 12501470
TI  - [Surgical treatment of "difficult" and complicated gastroduodenal ulcers].

PMID- 12501471
TI  - [Formation of a cicatrix of the liver].

PMID- 12501473
TI  - The mysteries of menopause.

PMID- 12501472
TI  - [Choice of a restoration method of gastrointestinal tract continuity: anatomic
      and functional substantiation].

PMID- 12501475
TI  - Facing the changes.

PMID- 12501474
TI  - The menopausal marketplace.

PMID- 12501476
TI  - Tailor-made treatments.

PMID- 12501477
TI  - Hormones and... many symptoms of menopause means many therapies.

PMID- 12501478
TI  - A world of differences.

PMID- 12501479
TI  - Assessing correlates of concern about developing Alzheimer's dementia among
      adults with no family history of the disease.
AB  - In an attempt to add to the knowledge about concerns regarding the development of
      Alzheimer's disease (AD), a sample of 186 Jewish and Arab adults with no family
      history of the disease were examined on the basis of sociodemographic and health
      characteristics, social-cognitive determinants, and knowledge about AD. Nearly 50
      percent of the participants reported being very concerned about developing AD.
      Memory problems and the likelihood of developing the disease emerged as
      significant predictors of concern about AD. The need to expand the use of
      theoretically-based models, including social-cognitive determinants, for the
      study of specific concerns about AD as a basis for the development of educational
      programs is discussed.

PMID- 12501480
TI  - Depression and Alzheimer's disease: symptom or comorbidity?
AB  - Alzheimer's disease is the most frequent form of dementia, where behavioral and
      cognitive disruption symptoms coexist. Depression, apathy, anxiety, and other
      conduct disorders are the complaints most often reported by caregivers. Fifty
      subjects were referred to our Institute with a diagnosis of probable Alzheimer's
      disease. Cognitive impairment was equally distributed among the subjects.
      Patients, aged 68 to 76 years old, were randomized to receive inhibitors of
      cholinesterase (Donepezil, 5 mg/day) alone, or inhibitors of cholinesterase plus
      selective serotonin reuptake inhibitors (SSRIs) (citalopram HBr, 20 mg/day). We
      followed up all the patients for one year, with particular concern for
      neuropsychological aspects associated with eventual behavioral changes. Results
      indicate that SSRI intake seems to be effective for depression, decreasing it and
      improving quality of life for both patients and caregivers. Side effects in both
      groups were few, and there were no study withdrawals. This paper discusses the
      relationship between dementia and depression, and presents our finding that
      depressive symptoms, if specifically treated, tend to reduce caregiver stress and
      improve well-being in patients with Alzheimer's disease.

PMID- 12501481
TI  - Treating learned helplessness in the elderly dementia patient: preliminary
      inquiry.
AB  - Learned helplessness is the psychological state that results when an individual
      who is unable to exercise reasonable mastery in one situation incorrectly assumes
      that he or she is then unable to exercise reasonable control in other situations
      as well. This may complicate the delivery of health interventions since the
      individual with learned helplessness may assume that no care provider or
      treatment intervention can be of assistance. Elderly patients with Alzheimer's
      disease and other dementias are not immune to this stance of learned
      helplessness. This paper presents one possible psychosocial rehabilitation
      approach, the Project SMART (Stress Management and Relaxation Training) program,
      to the problem of learned helplessness. Based on the skills of adaptive stress
      resistant problem solvers, Project SMART can be adapted to the needs of the
      elderly demented. The clinical and research implications are discussed.

PMID- 12501482
TI  - Impact of family members on nurse assistants: what helps, what hurts.
AB  - This qualitative study focuses on nurse assistant reports of both positive and
      negative behaviors exhibited by family members of cognitively impaired residents.
      The information reported is obtained from in-person interviews with 114 nurse
      assistants in 5 skilled nursing facilities (3 philanthropic, 2 proprietary) in
      Greater Cleveland, Ohio. Nurse assistants were predominantly female (89 percent),
      white (60 percent), with a mean age of 33, and had been caring for cognitively
      impaired nursing home residents for an average of five years. Content analyses of
      nurse assistants' responses reveal five categories of family members' positive
      behaviors and four categories of negative behaviors. This article focuses on
      these themes and suggests topics for educational interventions for family members
      and nurse assistants who care for cognitively impaired nursing home residents.
      Topics include coping with family members' feelings of guilt and related
      behaviors, understanding longstanding family relationship issues, and
      understanding possible reasons for decisions family members make regarding care
      of their relatives.

PMID- 12501483
TI  - Professional caregivers for patients with dementia: predictors of job and career
      commitment.
AB  - The purpose of this study is to identify what factors predict job and career
      commitment among professional caregivers working with patients with dementia. A
      secondary analysis was completed using data collected from 77 professional
      caregivers working in residential dementia special care programs. The findings
      suggest that professional caregivers' commitment to their jobs and careers is
      most closely related to their level of involvement in the interpersonal aspects
      of the work, the degree to which they feel personal growth or benefit, and the
      level of burden that their work generates. Strategies are suggested for improving
      job and career longevity among professional caregivers by enhancing attachment to
      patients and families, fostering professional identity and personal growth, and
      monitoring and managing professional caregiver burden.

PMID- 12501484
TI  - Therapeutic recreation interventions for need-driven dementia-compromised
      behaviors in community-dwelling elders.
AB  - This study describes a clinical trial of at-home recreational therapy for
      community dwelling older adults with dementia and disturbing behaviors. After two
      weeks of daily, individualized recreational therapy interventions (TRIs), results
      indicated a significant decrease in levels of both passivity and agitation.
      Biograph data collection was useful in identifying the physiological changes that
      occurred with each intervention technique. Specific information is included on
      the time of day each behavior occurred and the most effective interventions, as
      well as implications for service delivery.

PMID- 12501485
TI  - [Immunosuppresive agents, retinoids and new trends in the therapy of psoriasis].
AB  - Some psoriasis forms can be successfully treated with topical medicaments;
      serious and extensive forms cannot be cured without systemic treatment with
      retinoids (etretinate, acitretin, tazarotene) or with immunosuppressives
      (methotrexate, cyclosporine A, tacrolimus, SDZ 281-240). Immunotherapy and
      nucleotide analogues are being newly introduced, a number of potentially
      effective substances interfering with pathogenetic mechanisms participating in
      the emergence and self-prolongation of psoriasis are in the stage of research and
      clinical trials, and gene therapy possibilities are being investigated. The
      development and testing of drugs serving therapy for psoriasis correlates with
      the development of knowledge about the origins of the disease and the mechanisms
      of how antipsoriatics in current use as well as the new potential ones work.

PMID- 12501486
TI  - [What every worker involved in the synthesis and analysis of drugs could learn
      from the law concerning chemical substances and chemical preparations].
AB  - Commencing with 1 January 2000, law No. 157/98 of the Coll. in the wording of law
      352/99 of the Coll., government orders No. 25/99 of the Coll., 258/2001 of the
      collection, and other implementation regulations based on the regulations and
      directives of the European Community have been valid for the handling of chemical
      substances and preparations in the Czech Republic. The present paper discusses
      and comments on the parts of the law which are important for the management and
      running of the establishments engaged in the synthesis or analysis of drugs. It
      further lists examples of highly toxic chemical substances which can occur at
      these establishments.

PMID- 12501487
TI  - [The Baikal scullcap (Scutellaria baicalensis Georgi)--a potential source of new
      drugs].
AB  - The scullcap (Scutellaria baicalensis Georgi) is a medicinal plant of traditional
      Chinese medicine and the drug--Scutellariae radix--is, because of its
      antioxidant, antiviral, antibacterial, antiinflammatory, antiallergic, and
      sedative properties, the subject of intensive development. This paper reports the
      results of pharmacological-toxicological studies of this drug and its flavonids
      approximately from the year 1990 till the year 2001. The results confirm the
      validity of traditional use and at the same time indicate that some flavonoids
      have more utilizable therapeutic effects. Mainly baicalein seems to be a
      prospective medicine for the treatment of some kinds of cancer.

PMID- 12501488
TI  - [Reactive fractal dimension in the release of scopolamine bromide from hydrogel].
AB  - First-order release kinetics is characterized by a linear dependence of the
      release rate on the released amount of the active ingredient, the triple of the
      absolute value of the exponent of the exponential function expressing the
      reactive fractal dimension DR. Scopolamine bromide release from
      hydroxypropylmethylcellulose hydrogel was first expressed by first-order kinetics
      with an estimated DR ranging from 2.98-3.00. The employment of an exponential
      equation with the exponent of release n renders it possible to make an assumption
      about the mechanism of release. Within a range of n = 0.505-0.550, estimated DR =
      2.46-2.94. In this region, release by means of the mechanism of Fick's diffusion
      prevails. DR = (3/n)-3 generally holds true for the relationship between both
      variables, which makes it possible to use the knowledge gained in the
      experimental influencing of the exponent of release in the examination of the
      relationship between the reactive fractal dimension and the mechanism of release
      of scopolamine bromide from hydrogel. An increase in the exponent of release
      markedly decreases the corresponding values of reactive fractal dimension.

PMID- 12501489
TI  - [Analysis of the present status of conservative therapy of nephropathies].
AB  - Treatment by dialyzing represents an important contribution to the therapy of
      nephropathic patients. On the other hand, besides high financial costs it is not
      possible to forger significant social and psychic consequences of this therapy.
      The present paper aimed at a pharmacoeconomic evaluation of the costs of
      conservative treatment of nephropathic patients. The secondary aim was to compare
      the costs of conservative treatment in patients with markedly limited renal
      functions, creatinine clearance (Ccr < 0.4 ml/s), with those in patients with
      only slightly and medium-reduced renal functions (Ccr 0.4-1 ml/s). Health
      documentation from three nephrological out-patient surgeries was used to evaluate
      the results, the criterion for the selection of patients being a nephrological
      diagnosis with Ccr below 1 ml/s. The group comprised 102 patients aged 21-84
      years (average age being 63.99 years), including 56 females (54.9%) and 46 males
      (45.1%). According to the stage of renal disease, they were divided into two
      groups. The patients with slightly and medium-reduced renal functions (Ccr 0.4
      1.0 ml/s) represented nearly three quarters, whereas the patients with markedly
      reduced renal functions (Ccr < 0.4 ml/s) only slightly more than one quarter. In
      the group under study, the pharmacotherapeutic costs represented 2,889,778.0
      SK/year (28,331.16 SK/1 patient/1 day), in patients with renal insufficiency the
      costs being markedly higher (47,427.3 SK/1 patient/1 day in comparison with
      21,456.7 SK/1 patient/1 day). Of total pharmacotherapeutic costs, 29.38% was
      represented by antihypertensive agents, 24.47% by preparations supplementing
      essential amino acids, 14.83% by hypolipidemic agents, 14.37% by preparations
      supplementing calcium, 6.19% by antianaemic agents, and 7.76% by other drugs. The
      results demonstrate that pharmacotherapy of renal diseases is costly but in
      comparison with elimination methods (dialysis) it is incomparably less expensive.
      The spectrum of employed agents is in agreement with the present-day trends in
      conservative treatment which decelerates the progress of nephropathies.

PMID- 12501490
TI  - [Knowledge of patients about OTC drugs as a result of pharmacist-patients
      consultations].
AB  - Knowledge of patients about oral single-component OTC preparations containing
      ibuprofen, bought for their own use, was evaluated in relation to the manner of
      the process of communication between the pharmacist (laboratory assistant)-
      patient during the supply at the pharmacy. The answers of respondents were
      processed separately for the group of those who bought the preparation for the
      first time and those who had already used it for self-medication. The knowledge
      of contraindications and undesirable effects (judged separately) was found to be
      higher than 50% in both groups of respondents. Nevertheless, the patients who use
      the preparation repeatedly state simultaneous ignorance of undesirable effects
      and contraindications only in 32.2%, in contrast to the new users (60.0%). The
      patients who know neither contraindications nor undesirable effects of the
      preparation which they buy nevertheless think that they have enough information
      so that their self-medication can be safe (88.9% of patients using the
      preparation repeatedly and 80.0% of new users). Approximately a quarter of
      respondents in both groups under evaluation state that during the supply in the
      pharmacy they were not given any piece of information. Patients are passive when
      buying an OTC preparation and nearly 40% of them do not use the opportunity to
      ask for pertinent information themselves. Nearly 85% of respondents from both
      groups consider information gained from the pharmacy to be sufficient. When
      supplying an OTC preparation, in 45% of cases pharmacists (laboratory assistants)
      do not inquire whether the patient have already used the preparation, or whether
      he or she knows anything about it. The standard of counselling on self-medication
      in the Czech Republic should thus become more effective.

PMID- 12501491
TI  - [Anti-yeast activity of ethanol extracts of Lilium candidum L].
AB  - The paper deals with anti-yeast activity of ethanolic extracts from the flowers
      and bulbs of Lilium candidum L., Liliaceae, as well as some compounds isolated
      from these extracts. Several different methods were used for the determination of
      anti-yeast activity: Lowry method of protein determination, dilution and
      cultivation method. The extract from the bulbs was shown to be more active than
      the extract from the flowers, while isolated compounds were inactive against the
      tested yeasts.

PMID- 12501492
TI  - [Preparation of baculovirus transfer vectors for in vitro production of the
      P4501A1 and P4503A4 isoenzymes].
AB  - The aim of this work is the construction of an expression system for in vitro
      synthesis of microsomal monooxygenases P4501A1 and P4503A4, which catalyze
      oxidative transformations of most xenobiotics in both animal and human organisms.
      cDNAs encoding both proteins were obtained following the UBMTA protocol by the
      courtesy of holders, and amplified by established methods. Baculovirus transfer
      vectors were used to clone these cDNAs. These vectors contain a strong
      polyhedrine promoter surrounded by sequences homologous to that of baculovirus
      DNA, allowing the recombination of the vector with the viral DNA, and hence the
      production of a protein. Established methods and PCR were used to insert cDNA
      into the vectors, and the insertion was verified by the PCR method with specific
      primers and using restriction endonucleases.

PMID- 12501493
TI  - [Preparation and physico-chemical properties of alkyl esters of 2-, 3-, 4-(2
      hydroxy-3-[4-diphenylmethyl) piperazine-1-yl] propoxy) phenylcarbamide].
AB  - The paper is devoted to the synthesis and study of some physico-chemical
      properties of a group of substances--potential antagonists of beta-adrenergic
      receptors. The substances are derivatives of aryloxyaminopropanol, where the
      basic part consists of diphenylmethylpiperazine and the aromatic part is modified
      with alkyl esters (methyl to butyl) of carbamic acid in positions 2-, 3-, 4-. The
      representation of the elements was confirmed by elemental analysis. The
      substances were characterized by melting point, IR and UV spectra. Their
      solubility and surface activity were determined. The purity of prepared
      substances was examined by means of TLC.

PMID- 12501494
TI  - [Therapy of hyperhomocysteinemia with vitamin B12].
AB  - Prevalence of mild hyperhomocysteinemia in vegetarians and vegans is a
      consequence of vitamin B12 deficiency. Clinical study of homocysteine reduction
      by vitamin B12 consisted of subjective healthy adults on alternative nutrition (n
      = 9) with vitamin B12 deficiency and with mild hyperhomocysteinemia. Vitamin B12
      treatment was implemented by 5 intramuscular cyanocobalamin injections of a total
      content of 2200 micrograms during two weeks. Homocysteine level was significantly
      reduced (from 22 mumol/l to 11.7 mumol/l; individual reduction 29-55%). Vitamin
      B12 concentration in blood was significantly increased (from 152 pmol/l to 277
      pmol/l; individual % of increase 63-150). The results show a high effect of
      vitamin B12 treatment in homocysteine value reduction of subjects on alternative
      nutrition.

PMID- 12501495
TI  - [What is your diagnosis? Mature contorted teratoma of the left ovary].

PMID- 12501496
TI  - [Etiology and pathogenesis of inflammatory bowel diseases].
AB  - Based on the data presented and numerous others it can be stated that genetic
      susceptibility as well as environmental influences are generally accepted. It is
      consensus that we have to deal with a number of patient subpopulations indicating
      that Crohn's disease and ulcerative colitis are syndromes and not single disease
      entities. It is also clear that the enteric flora is of importance which leads to
      attempts to modulate gut contents. Alternative etiologic concepts such as primary
      barrier defects or abnormal transport processes in liver and upper intestine
      should be considered.

PMID- 12501497
TI  - [Inflammatory bowel diseases: diagnosis (including new procedures for small
      intestine examination)].
AB  - Medical history, clinical examination, general laboratory data and microbial
      stool examinations are basic diagnostics in inflammatory bowel diseases. Specific
      immunologic parameters can make classification easier in indefinite disease,
      their use is still in an experimental state. Ultrasound and endoscopic
      examinations have largely replaced conventional radiological procedures. For the
      experienced examiner, ultrasound allows assessment of small bowel and colon as
      well as other organs. Ileo-colonoscopy with biopsies remains the gold standard in
      the diagnosis of inflammatory bowel diseases. For small bowel examination, modern
      methods like push-enteroscopy, capsule endoscopy or the Hydro-MRI can be
      employed. At the moment, their usage is limited to specialized centers. Because
      of its broad availability small bowel follow through is still the standard in
      small bowel examination. After 8 years of colitis ulcerosa, ileo-colonoscopy with
      biopsy should be performed every year according to the guidelines. If these
      recommendations also apply to Crohn's disease is not sure yet.

PMID- 12501498
TI  - [Therapy of chronic inflammatory bowel diseases].
AB  - The standard therapy in Crohn's disease and ulcerative colitis is based on
      corticosteroids and aminosalicylates. Chronic active as well as fulminant disease
      usually require immunosuppressive therapy. The new biological have mostly
      disappointed because of lacking efficacy (Il-10, IL-11 or others) or serious
      adverse events (infliximab).

PMID- 12501499
TI  - [Diet therapy in chronic inflammatory bowel disease: results from meta-analysis
      and randomized controlled trials].
AB  - BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel
      diseases of unknown etiology. Unspecific immunosuppressive therapy represents
      current standard treatment and is often associated with severe side effects.
      Several treatment regimens have been evaluated to identify alternative
      therapeutic options. Among these different diet therapies were investigated.
      Objective of this paper is to review the results of diet therapy in chronic
      inflammatory bowel disease on the basis of randomised controlled trials and meta
      analysis of randomised controlled trials. METHODS: Medline and Cochrane Library
      were searched for meta-analysis and randomised controlled trials investigating
      this question. Additionally reference lists of identified articles and text books
      were checked for further trials. RESULTS: Four meta-analyses investigated the
      treatment of acute Crohn's disease with elemental-, semi-elemental-, and
      polymeric diets in comparison to corticosteroids or to another form of enteral
      diet. All meta-analyses show a superiority of corticosteroids and no difference
      in the effect of the compared enteral diets. Randomised controlled trials
      investigating diet therapy in ulcerative colitis have not been summarised in a
      meta-analysis yet. Eleven randomised trials were identified which evaluated diets
      in ulcerative colitis patients: Dietary supplementation with n-3-fatty acids (6
      trials), elemental diet [2], dietary supplementation with dietary fiber [1],
      elimination diet [1], and dietary supplementation with olestra [1]. Only for the
      elimination diet a significant positive effect on the course of disease was found
      in one trial which investigated only 18 patients. CONCLUSIONS: Enteral
      nutritional therapy of acute Crohn's disease is less effective than treatment
      with corticosteroids. In case of severe steroid induced side effects diet
      treatment can present a promising alternative. Superiority of one of the
      investigated different formulations was not found. Meta-analyses of randomised
      trials provide a clear and easy to understand presentation of the effect of this
      intervention. Eleven published trials investigating the effect of diets in
      ulcerative colitis show only for elimination diet a positive treatment effect.
      The trials do find a positive effect of one of the other interventions but the
      trials are very small and cannot exclude a treatment effect. Meta-analysis of
      these trials would be helpful for a better presentation and understanding of
      these results.

PMID- 12501500
TI  - [The Archangel'skoe Central Military Clinical Sanatorium].

PMID- 12501501
TI  - [New aspects of the pathogenesis of cholesterol cholelithiasis].
AB  - During the last few years our knowledge of the pathogenesis of cholesterol
      gallstone disease has dramatically changed. Only a decade ago this topic was
      considered as already explored and scientifically not very interesting. However,
      with the progress in the field of lipid metabolism, the views on the
      aetiopathogenesis of cholelithiasis and particularly on its genetic aspects
      appear to be revolutionary. The predominant pathogenetic factor turned up to be
      the biliary cholesterol supersaturation, which is influenced by biliary secretion
      of the three major components of bile--cholesterol, phospholipids and bile salts.
      During the last years biliary secretion of these biliary lipids has been studied
      thoroughly and genetic mechanisms leading to the disorder of the biliary lipids
      homeostasis have been described. These novel aspects are discussed in the review
      article presented.

PMID- 12501502
TI  - [Transforming growth factor (TGF-beta) and kidney transplantation].
AB  - Transformation growth factor (TGF-beta) is a cytokine, which takes part in many
      clinical conditions linked to different chronic disease states. Its production is
      regulated by genes and polymorphism of TGF-beta gene individually predetermines
      levels of its production. TGF-beta is produced by a number of normal,
      predominately haemopoietic and tissue cells. Moreover, it controls cell
      proliferation and differentiation, and namely it stimulates fibrogenesis.
      Profibrogenic efficacy plays a physiological role in wound healing and it is
      implicated in a spectrum of disease states, such as diabetic nephropathy, chronic
      glomerulonepthritis, lung fibrosis, or postirradiation fibrosis. In kidney
      transplant recipients. TGF-beta has been suggested to be involved in the chronic
      rejection pathogenesis by enhancing fibrogenesis.

PMID- 12501503
TI  - [Less common risk factors for atherogenesis--homocysteine, lipoprotein (a) and C
      reactive protein].
AB  - Atherosclerosis and its complications belong to the most frequent causes of
      morbidity and mortality in the developed countries. Far from all cases of early
      atherosclerosis can be explained by presence of "classical" risk factors
      (hypertension, hypercholesterolemia, and namely by oxidised forms of lipoproteins
      of low density, by smoking or due to not fully compensated diabetes mellitus).
      Our review brings information of another three serious risk factors-
      homocysteine, lipoprotein (a), and highly sensitive C-reactive protein. Metabolic
      relations among them are given as well as results of comparatively independent
      clinical studies and possibilities to influence these risk factors. Though they
      are comparatively independent, one feature connects them--they participate
      significantly on the development of endothelial dysfunction, which is supposed to
      be the initial stadium of atherogenesis.

PMID- 12501504
TI  - [Benign stenoses of the large respiratory airways].
AB  - BACKGROUND: Benign stenoses of main respiratory pathways develop usually in
      patients after intubation or tracheostomy. Incidence of such states is not known,
      they are frequently diagnosed too late, and there are different views of their
      treatment. In order to contribute to the improvement of our knowledge of this
      serious impairment we followed prospectively all patients with this diagnose at
      our department since March 1998. METHODS AND RESULTS: The group of 31 patients
      with benign stenoses of non-tumorous origin diagnosed and treated at the TRN of
      the Teaching Hospital Motol in years 1998 to 2000 consisted of 24 males and 7
      females, age median was 52 years. Stenosis was caused in 27 patients by
      intubation, in 4 patients by some other causes. At admission we performed in 30
      patients electrocauterization and dilatation of stenosis, one patient was
      immediately indicated for surgery. Beside two cases we always achieved sufficient
      patency of stenosis and weighted indication to surgery. We sent for surgery 15
      patients, 10 patients were permanently healed using methods of interventional
      bronchoscopy, including introduction of stent in 6 cases. From the remaining 6
      patients, two of them are planned for resection of stenosis, four are inoperable
      from various reasons, and two died of causes not related to stenosis.
      CONCLUSIONS: Based on our experience we recommend as an optimal management of
      such patients is the dilatation or removal of stenosis and then always to
      consider resection of trachea. In inoperable cases methods of interventional
      bronchoscopy should be used. Authors recommend sending all patients intubated
      longer than 2 days for bronchoscopic examination in interval of 2 months.

PMID- 12501505
TI  - [Symptomatology and specific characteristics of chronic gastritis caused by
      Helicobacter pylori infection in children in the Czech population--epidemiologic,
      clinical, endoscopic and histomorphologic study].
AB  - BACKGROUND: H. pylori infection is associated with gastritis and peptic ulcer in
      children and adults. H. pylori acquisition seems to occur predominantly in
      childhood. Some data have reported H. pylori non-related chronic gastritis.
      Little information is available about the relationship between H. pylori,
      clinicopathologic features and long-term effects of infection in childhood. The
      purpose of this study was to compare the differences between chronic gastritis
      due to H. pylori with those of chronic gastritis not associated with H. pylori
      infection. METHODS AND RESULTS: 92 children (13.8 +/- 3.5 years) were take into
      they shaded group. 51 children were H. pylori positive, 41 children had no
      evidence of H. pylori. Epidemiological and clinical data, endoscopic appearance
      and histologic examination were evaluated. There were no differences in age and
      gender among the children. There was a significant correlation between H. pylori
      infection and parental education (p < 0.05) and habitat crowding (the number of
      rooms). There were no differences in clinical diagnosis and occurrence of any
      predominant symptom between the two groups. There was an association with a
      detrimental influence on daily life and activities in H. pylori patients (p <
      0.01). Extradigestive symptoms (chronic urticaria, sideropenic anemia) were
      significantly more common in the H. pylori positive group (p < 0.05). 21 children
      (41.6%) were H. pylori positive/cagA positive, 15 of them (30.3%) were H. pylori
      positive/vacA positive. Findings of antral nodularity were more frequent in H.
      pylori positive children than in H. pylori negative (p < 0.000001). There were no
      differences in erythematous gastritis, haemorrhage and mucosal ulceration. H.
      pylori density score did not differ in various part of the gastric mucosa
      (antrum, corpus). Chronic gastritis was found to be more severe in patients with
      H. pylori infection compared with H. pylori-negative gastritis. Statistically
      significant was the increased presence of neutrophils, edema, monocytes, lymphoid
      follicles, the intensity of inflammation and mucosal oedema in the gastric mucosa
      in H. pylori positive children. There were no differences in the incidence of
      foveolar hyperplasia, mucosal atrophy, intestinal metaplasia and erosion.
      CONCLUSION: H. pylori related chronic gastritis may be considered as a specific
      form of inflammation and it may be associated with a typical clinical
      symptomatology in a subgroup of children in Czech population. Precautions in life
      style may diminish H. pylori-related disease in children.

PMID- 12501506
TI  - [Cardiology 2001].
AB  - A review of the most important topics published during 2001 is presented. The
      Writing Committee of the American College of Cardiology and the American Heart
      Association decided to take a new approach to the classification of heart failure
      that emphasizes both the evolution and the progression of the disease, using
      potential risk factors and structural disorders as criteria to identify the
      severity of a heart failure syndrome. Similarly, an ACC/AHA Clinical Competence
      Statement on electrocardiography and ambulatory electrocardiography was published
      with a special emphasis on the computer interpretation of the electrocardiogram.
      Since various drugs were shown to induce electrocardiographic abnormalities as
      e.g. QT prolongation associated with ventricular tachycardias, the FDA decided to
      introduce higher regulatory requirements on the cardiac safety of novel drugs. In
      cardiovascular surgery Octopus off-pump bypass was demonstrated to be a safe
      procedure for carefully selected patients with multivessel coronary heart
      disease. Because of the extensive progress made in cardiovascular surgery, the
      management of severe heart failure has to be improved and early effective
      preventive measures have to be introduced to reduce the risk of intractable heart
      failure. The "New guidelines for evaluating acute coronary syndrome" stress the
      importance of early identifying and early treatment, including invasive strategy
      as PTCA with stenting.

PMID- 12501507
TI  - The first patient.

PMID- 12501508
TI  - Now, 'integrative' care.

PMID- 12501509
TI  - Cardiac disease. Ways to heal your heart.

PMID- 12501510
TI  - Osteoarthritis. Options for arthritis pain.

PMID- 12501511
TI  - Learning from China.

PMID- 12501512
TI  - Back pain. Beyond the backache.

PMID- 12501513
TI  - Ginkgo on your mind? It may ease dementia, but nothing's definite.

PMID- 12501514
TI  - For the littlest patients.

PMID- 12501515
TI  - A natural way to age.

PMID- 12501516
TI  - How to lift the mind.

PMID- 12501517
TI  - Anxiety and depression. Natural mood remedies.

PMID- 12501518
TI  - Pondering the placebo effect.

PMID- 12501519
TI  - Research. Finding out what works.

PMID- 12501520
TI  - Yoga and massage: if it's physical, it's therapy.

PMID- 12501521
TI  - Should we opt out of organ donation?

PMID- 12501522
TI  - When the truth hurts.

PMID- 12501523
TI  - A solution-focused approach to engagement in acute psychiatry.
AB  - Mental health nurses working in acute wards need to be able to engage with
      patients, yet this is becoming increasingly difficult to do. With discharge plans
      often made as soon as patients arrive, and discharges precipitated by demand for
      beds, how do nurses engage patients and what do they engage them in? Solution
      focused communication skills can help in this respect. The techniques are simple
      and not time-consuming and give nurses a clear sense of a therapeutic role. This
      article discusses how solution-focused approaches benefit patients and nurses.

PMID- 12501524
TI  - What you need to know about ... varicose veins.

PMID- 12501525
TI  - Use of oxygen.

PMID- 12501526
TI  - Person-centred care in dementia.
AB  - People with dementia, particularly in its early stages, are aware of their
      problems, therefore it is vital that they are told of their diagnosis so they can
      make decisions about their future. The development of new drugs has led to major
      changes in the management of dementia, but 'postcode prescribing' means that all
      drugs are not widely available. Various means of support are available for
      patients and their carers but at all times healthcare professionals must ensure
      that the person is at the centre of a patient's care.

PMID- 12501527
TI  - Support and education: the role of the domestic violence coordinator.
AB  - The domestic violence coordinator is a relatively new role that has evolved due
      to increased awareness of the long-term health issues that result from domestic
      abuse. Health professionals have a vital role in the identification, assessment
      and response to domestic violence. In order to provide this support the
      professionals themselves require the appropriate knowledge and skills. The
      domestic violence coordinator's role is multifaceted; it incorporates effective
      education and training, and provides the essential link between clinical and
      community environments.

PMID- 12501528
TI  - Domestic violence in nursing curricula.
AB  - Domestic violence has serious consequences, which often result in long-term
      damage to an individual's health, well being and development. Health care
      providers are ideally placed to detect people who have experienced domestic
      abuse, as almost everyone accesses the health service at some point in their
      lifetime. Nursing and midwifery tutors have a pivotal role in educating health
      care professionals on the subject of domestic abuse. This article reports on a
      study exploring the current practice and views of tutors who deliver this topic
      in the curriculum.

PMID- 12501529
TI  - Home delivery.

PMID- 12501530
TI  - A nurse in the house. Interview by Peter Cross.

PMID- 12501531
TI  - Government policy and older people.
AB  - Older people are the main users of health and social care services, but services
      have not always adequately addressed need (Department of Health, 2001). The past
      50 years have witnessed many changes and reforms in health and the social welfare
      state that have directly affected older people and the level and type of help and
      support they can expect from the state. Nurses need to understand these changes,
      as the implications of policy development will have a direct impact on the people
      we are working with. Nurses also have a part to play in shaping and informing
      policy development.

PMID- 12501532
TI  - Intermittent self-catheterisation.
AB  - Intermittent self-catheterisation (ISC) or carer/nurse-assisted clinically clean
      intermittent catheterisation (CCIC) has developed over the past 20 years as a
      means of treating patients with bladder-emptying problems. It is now recognised
      as one of the safest methods of managing patients, especially those with
      neurogenic bladder disorders. ISC has been demonstrated to reduce infection
      hazards and greatly improve the lives of many patients with micturition disorders
      (Lapides et al, 1972).

PMID- 12501533
TI  - Teaching ISC technique.
AB  - Intermittent self-catheterisation (ISC) is an extremely intimate technique and
      those teaching it must be aware of both verbal and non-verbal behaviour by
      patients throughout the procedure. The instructor needs to be empathetic,
      supportive and skilled in the technique, as the patient faces a change in both
      lifestyle and body image. Psychosexual awareness means being alert to any sexual
      anxieties the patient may have.

PMID- 12501534
TI  - Osteoporosis.
AB  - In 2001 the National Service Framework for Older People was launched and included
      a standard to reduce the number of falls and their impact through strategies
      encompassing the prevention and treatment of osteoporosis (Department of Health,
      2001).

PMID- 12501535
TI  - Relieving pressure.
AB  - Mrs Smith has been resident on a continuing care ward for approximately six
      years. She was originally admitted after a left cerebral vascular accident that
      resulted in a right-sided hemiplegia. She is dysphasic but appears to understand
      much of what is said to her, and she is continent of urine and faeces, using
      facial expressions and body gestures to communicate her needs. In recent years
      her weight has increased from 63 kg to 83 kg and she is now chairbound, following
      a recent leg fracture.

PMID- 12501536
TI  - Attention deficit hyperactivity disorder.

PMID- 12501537
TI  - Ageing males. An emerging area of concern.

PMID- 12501538
TI  - Learning may provide neuroprotection against dementia.
AB  - A number of studies attempting to identify specific risk factors for dementia
      have noted an inverse relationship between educational background and the
      likelihood of developing dementia. This idea has been somewhat controversial as
      educational background can introduce a number of confounding factors that
      generally affect health and lifestyle. Despite these reservations, there is
      mounting evidence to support the concept of education (or increased mental
      activity) producing a functional reserve in the brain, a process that provides
      some protection against the clinical manifestation of dementia. Long-term
      potentiation (LTP) is a recognized neural correlate of learning and memory. We
      have shown recently that LTP reduces the sensitivity of hippocampal neurons to
      agonists of the neurotransmitter glutamate; additionally, we have reported that
      LTP protects the neurons from the effects of acute hypoxia. Given that the effect
      of hypoxia on neurons involves over-stimulation by glutamate, and hypoxia has
      been implicated in the aetio-pathology of some types of dementia, our
      observations suggest that LTP has a protective effect on neuronal tissue. Such an
      interaction offers a physiological basis for the epidemiological evidence that
      lifelong learning can protect a person from some types of dementia.

PMID- 12501539
TI  - Primary malnutrition. Can we always tell?
AB  - Patterns of disease in the English-speaking Caribbean have changed considerably
      over the past two decades. There has been a decrease in the incidence of common
      infectious diseases, an increase in the prevalence of chronic non-communicable
      disorders and an increase in the incidence and prevalence of HIV/AIDS. However,
      published estimates suggest that malnutrition continues to be a serious public
      health problem. It is possible that changing patterns of disease within the
      epidemiological transition may affect patterns of presentation of severe forms of
      childhood malnutrition. We have examined records of 435 children admitted to the
      clinical research ward of the Tropical Metabolism Research Unit (TMRU) from
      January 1, 1990, to December 31, 1999; among these were 25 children who were
      subsequently found to have severe childhood malnutrition (SCM) due to a defined
      medical or surgical disorder (i.e. secondary SCM). Among children with secondary
      SCM, the HIV/AIDS group was the largest and comprised 60% of these admissions.
      Regression analyses show that, over the ten-year period, there was a small, non
      significant decline in the number of cases of primary SCM (incidence rate ratio,
      IRR = 0.99, 95% confidence interval = 0.96, 1.02, p = 0.98), while the number of
      cases of secondary SCM increased (IRR = 1.18, 95% CI = 1.03, 1.35, p = 0.02).
      These data are indicative of the need for continued vigilance in the evaluation
      of children who have clinical features of the syndromes of severe malnutrition
      and draw attention to the potential impact of HIV/AIDS in yet another area of
      healthcare delivery.

PMID- 12501540
TI  - Autoantibodies, human T lymphotropic virus type 1 and type 1 diabetes mellitus in
      Jamaicans.
AB  - The clinical characteristics, autoantibody profiles and seroprevalence of human T
      lymphotropic virus Type 1 (HTLV-1) were assessed in 30 Jamaican patients with
      Type 1 diabetes mellitus. Two hundred and fifty-two blood donors and 108 patients
      with Graves' disease were included as controls for the HTLV-1 component of the
      study. The mean age of onset of diabetes mellitus was 20.5 +/- 9.2 years and the
      mean duration of diabetes mellitus was 10.5 +/- 6.1 years. The remarkable
      clinical data included an absence of other associated organ-specific autoimmune
      diseases, and clinical evidence and history of congenital rubella in one patient.
      Islet cell cytoplasmic antibodies (ICA) were absent but 17% (5/30) of the
      diabetic patients tested positive for glutamic acid decarboxylase (GAD)
      antibodies. No other organ-specific autoantibodies were detected but non-organ
      specific autoantibodies were present in 9 (30%) of the sera of diabetic patients.
      The seroprevalence of HTLV-1 in the patients with diabetes mellitus was
      significantly higher than that in the healthy controls (17% (5/30) versus 4%
      (11/252), p = 0.05). Autoantibodies were found in the sera of 4/5 (80%) of the
      diabetic patients who were positive for HTLV-1. None of the patients with onset
      of diabetes mellitus below age 15 years was HTLV-1 positive. The likely
      polyaetiological nature of Type 1 diabetes mellitus in Jamaicans is being further
      investigated at the molecular level.

PMID- 12501541
TI  - A survey of cutlass ("Collins") injuries seen in the emergency department of the
      Queen Elizabeth Hospital in Barbados.
AB  - For the period March to November 1998 inclusive, a prospective survey was
      conducted of all patients who sustained injuries with a cutlass or machete and
      were admitted to the Accident and Emergency Department of the Queen Elizabeth
      Hospital. Of the 77 patient admissions, 81% (62/77) were male. The average age
      was 28.8 years (range 8 to 73 years; standard deviation 13.1). Twenty-two per
      cent of the patients were less than 20 years old. The most common locations of
      the lacerations were upper extremity (59 lacerations) and scalp (16 lacerations).
      Thirty-four per cent of the patients (26/77) sustained lacerations to two or more
      anatomical locations. There were 23 fractures in 21 patients; skull fractures
      were the most common fractures (11). Of the 63 patients who responded to the
      question on whether they knew the identity of their assailants, 51 reported that
      they were attacked by someone known to them; eight were assaulted by a spouse or
      known family member. Eighty-six per cent of patients (66/77) were treated in the
      emergency room and discharged. Of the 11 patients admitted, eight required
      treatment in the operating theatre. The average length of stay was 3.6 days.
      There were no amputations or deaths. One patient sustained loss of vision in one
      eye. In Barbados, most victims of cutlass injuries are males who know their
      assailants and the morbidity is most often related to head injuries and to short
      term physical disability due especially to lacerations of the hand and forearm.

PMID- 12501542
TI  - Lead pollution and amelioration measures in the community of Frazers Content, St
      Catherine, Jamaica.
AB  - Lead poisoning, especially in children, is a preventable disease. Many children
      are exposed to this hazard, especially in poor communities, because of a paucity
      of information on lead poisoning and increasing economic hardships. In 1994, the
      case of the poor suburban community of Frazers Content, St Catherine, Jamaica,
      came to the public attention because of the high frequency of hospital
      admissions, or outpatient treatment, of children for lead poisoning. This paper
      reviews a Blue Cross of Jamaica-led-initiative aimed at the clean up and
      education of the Frazers Content community. The following four-pronged approach
      was employed: environmental and biological sampling and sample analysis, health
      education, decontamination and community clean up and entrepreneurial activities.
      The project outputs included: training of 17 community wardens and 22
      schoolteachers; the clean up of 64 residences which had lead levels in excess of
      500 ppm; the establishment of an entombment site for the contaminated soil in
      accordance with the Jamaica Natural Resources Conservation Authority and training
      of residents in entrepreneurial skills, chicken and rabbit rearing and nursery
      establishment. The paper includes discussion of the lessons learnt and
      recommendations for future action.

PMID- 12501543
TI  - Complementary medicine seminar for medical undergraduates at the University of
      the West Indies, Mona.
AB  - Use of complementary medicine by the general public is increasing. It is
      therefore apt that doctors in training learn more about it. For several years,
      medical students doing their Year III Community Health clerkship have had one
      afternoon devoted to the subject. In advance, they are given reading materials
      and are asked to prepare short presentations relating to definitions, types of
      therapies available, principles underlying some of these therapies, extent of
      usage of complementary medicine, expenditure on it, appropriate research methods
      to evaluate effectiveness, and opinions of the public and the profession
      regarding its use. A demonstration of one kind of complementary medicine by a
      practising therapist forms part of the activities.

PMID- 12501544
TI  - Trauma care in Jamaica. A time for decision.
AB  - The high incidence of trauma in Jamaica is well documented. Trauma accounts for
      approximately 40 per cent of the workload in both the Accident and Emergency Unit
      and the surgical wards at the University Hospital of the West Indies. The death
      rates for motor vehicle accidents and homicide in Jamaica are greater than those
      in developed countries as well as the rest of the Caribbean region. Many of these
      deaths occur before the patient reaches hospital. Preventative measures and
      improved pre-hospital care will reduce these deaths and also lessen the burden
      injuries place on the health service. In hospitals, most preventable deaths occur
      within the first few hours of admission. An organized system of care which
      ensures that the right patient is taken to the right hospital at the right time
      as well as training in Advanced Trauma Life Support should reduce the preventable
      death rate. Collaboration is needed between health workers and other concerned
      groups to stimulate an interest in injury prevention and improvement in trauma
      care.

PMID- 12501545
TI  - Tobacco smoking in the Caribbean. The role of dental professionals in smoking
      cessation programmes.
AB  - Cigarette smoking constitutes the most common form of tobacco use in the western
      world. Although the prevalence in the Caribbean is lower compared with Latin
      American and North American countries, cigarette smoking is gaining popularity
      with adolescents in the Caribbean. Tobacco smoking is injurious to general and
      oral health and is responsible for at least ten per cent of all deaths in the
      English-speaking Caribbean countries. These observations imply an urgent need to
      implement anti-smoking programmes in this region. Such programmes should focus on
      prevention of the acquisition of tobacco smoking habits, implementing smoking
      cessation programmes and providing support for those who have quit smoking. A
      variety of approaches involving health professionals, government and non
      governmental agencies, media and other interest groups is required to address
      this issue. This paper proposes a strategy for a smoking cessation programme in
      the Caribbean that should be incorporated in day-to-day general dental practice.

PMID- 12501546
TI  - Making a diagnosis of adult attention deficit hyperactivity disorder.
AB  - This paper describes the diagnosis of adult attention deficit hyperactivity
      disorder (ADHD) in a 26-year-old female. Adult ADHD is being increasingly
      acknowledged as a cause of psychiatric morbidity particularly since the diagnosis
      is frequently missed in childhood. Greater recognition of this disorder is
      important because it can be a cause of low productivity and employment disruption
      as well as a risk factor for other psychiatric problems such as substance abuse
      and mood disorders.

PMID- 12501547
TI  - Treatment of pilon fractures using the Ilizarov technique. Case reports and
      review of the literature.
AB  - Tibial pilon fractures are difficult to manage because of their severity. These
      injuries are frequently open and contaminated, with marked comminution of the
      articular surface and metaphysis. The results of open reduction and internal
      fixation are dependent on the severity of the initial injury and the quality and
      stability of the reduction. The literature reports numerous complication rates
      associated with open reduction and internal fixation of pilon fractures. The
      Ilizarov technique of external fixation has fewer complications, and allows
      restoration of joint surfaces, reconstruction of length, and alignment of the
      extremity while maintaining a sufficient range of joint motion. Two cases of
      pilon fractures in which the Ilizarov method was utilized are reported, along
      with a review of the literature.

PMID- 12501548
TI  - Accidental implantation of a bur tip in the elbow of a dentist. A possible
      pathway for inoculation with deadly infectious agent.
AB  - The most common source of occupational injury to dentists is percutaneous
      puncture of the hands from "sharps". We report a percutaneous injury involving a
      dentist where the tip of a dental bur became implanted in his elbow. The dentist
      had been vaccinated against Hepatitis B and both the patient and dentist were Hiv
      and Hepatitis B seronegative immediately after the incident. Surgical exploration
      of the dentist's elbow the following day was unsuccessful in locating the bur
      tip. The dentist remains healthy and is not incapacitated as a result of the
      injury, despite retention of the bur tip. This accident has implications for
      modifying the design of present and future dental units. We are not aware of a
      previous report of this type of injury.

PMID- 12501549
TI  - Lumbar spine synovial cysts. A case report and review of the literature.
AB  - This paper reports the case of a sixty-year-old man who presented with backache
      and radiculopathy secondary to the development of a lumbar spinal synovial cyst
      following an episode of trauma. There was resection of the cyst with partial
      facetectomy. Current literature reports are outlined.

PMID- 12501550
TI  - Antenatal diagnosis of a choledochal cyst. Case management and literature review.
AB  - Antenatal abdomino-pelvic ultrasound done on a 36-year-old woman at 19 weeks'
      gestation revealed a subhepatic cyst in the foetus. Postnatally, a type I
      choledochal cyst was confirmed in the newborn female infant. Biliary obstruction
      necessitated cyst excision and hepaticojejunostomy at age 16 days. We recommend
      early surgical intervention for neonates with choledochal cysts manifesting
      objective evidence of biliary obstruction. Non-obstructed patients are best
      explored later (> three months of age) when the risk of iatrogenic injury to the
      biliary tree and hepatic vessels is reduced.

PMID- 12501551
TI  - Scleroderma with cardiac tamponade, hyperthyroidism and incidental papillary
      thyroid carcinoma.
AB  - Cardiac tamponade and malignancy are associated with a poor prognosis in
      Progressive Systemic Sclerosis (PSS). We present the case of a 31-year-old
      African-Jamaican woman with PSS and a thyroid neoplasm who presented with cardiac
      tamponade requiring pericardiocentesis. Despite the presence of two poor
      prognostic markers, she has had a favourable postoperative course.

PMID- 12501552
TI  - A childhood malignant rhabdoid tumour of the kidney.
AB  - A case report is presented of a malignant rhabdoid tumour occurring in the kidney
      of a 23-month-old boy. Important differences between this and the conventional
      Wilms' tumour include the histological demonstration of sheets or cords of large
      cells resembling myoblasts, a tendency to frequent clinical relapse, and a high
      mortality rate despite multimodal therapy. In this child, an encouraging initial
      response to pre-operative chemotherapy, followed by surgical excision and
      postoperative triple chemotherapy, was not sustained. Recurrence of pulmonary
      metastases did not respond to further chemotherapy and whole lung irradiation.

PMID- 12501553
TI  - Disseminated donovanosis (granuloma inguinale) with osteomyelitis of both wrists.
AB  - Donovanosis is a sexually transmitted infection which presents with genital
      ulceration and inguinal lymphadenopathy. Rarely, it presents with extra-genital
      manifestations. We present a case of disseminated donovanosis with cervical
      ulceration, massive pelvic lymphadenopathy, osteomyelitis of the wrists and
      septic arthritis of the knees and right elbow. A 23-year-old gravida two
      presented with wasting, oedema, ascites, bilateral iliac lymphadenopathy, anaemia
      and a large ulcer of the cervix uteri. Two months later in the outpatient clinic,
      she was much improved but still had post-coital bleeding and a hyperaemic cervix,
      suggestive of persistent infection. The course of antibiotics was therefore
      repeated. Histopathological examination of a specimen from colposcopic biopsy of
      the cervix uteri revealed granuloma inguinale. She improved after several courses
      of antibiotics, blood transfusion, surgical debridement and aspiration of
      affected joints.

PMID- 12501554
TI  - The sexual behaviour of youth in Tobago. A report on the development of a health
      promotion project.
AB  - The development of a health promotion project to meet the sexual health needs of
      youth in Tobago is described. Quantitative and qualitative research was conducted
      by and with young people, followed by a process of feedback and consultation with
      adult and youth stakeholders. Key results of the sexual health research are
      presented.

PMID- 12501555
TI  - Image and diagnosis. Carcinoid tumor of the lung.

PMID- 12501556
TI  - The concealed cystic duct--a significant cause of common bile duct injury in
      laparoscopic cholecystectomy.

PMID- 12501557
TI  - HIV in Jamaica: are we being alarmist?

PMID- 12501558
TI  - [Change of approach in tumor therapy: role of percutaneous and vascular ablation
      in the treatment of advanced primary and secondary liver cancer].
AB  - The palliative treatment of primary and secondary hepatic carcinomas is required
      if surgical ablation is not possible. In practice, screening and follow up of
      even the endangered population are insufficient. This is why, in most cases, the
      hepatic carcinomas are diagnosed only at an advanced stage when surgical therapy
      is hardly possible. The interventional radiological methods, percutaneous and
      vascular ablations are frequently used for palliative treatment. In that case if
      the diameters of the tumors are less than 4-5 cm and the number of the lesions is
      less than 5, radiofrequency ablation is the best choice. At a more advanced
      stage, local intraarterial chemotherapy chemoembolization and occlusion of the
      feeding artery combined with systemic chemotherapy can be performed. The author
      reveals the therapeutic methods, indications, possible combinations and the
      prospective results. According to the latest literature, it is pointed out that
      the described therapeutic methods are effective and parts of the complex oncology
      treatment. These applications are not optional since long and quality of life of
      the patients are much worse without complex treatment.

PMID- 12501559
TI  - [New diagnostic and classification system in diabetic syndrome].
AB  - Diabetes mellitus is a heterogeneous disorder. Evidence for heterogeneity is
      based on measuring endogenous insulin level since some forty years ago. Insulin
      is lacking at the time of diagnosis in most patients, whose disease started
      rapidly, with classical symptoms, and who are mainly children, adolescents or
      young adults. In the majority of middle-aged, obese diabetics, insulin levels are
      frequently high at diagnosis. Since insulin measuring from sera became a routine
      laboratory test these two main types were nominated as insulin-dependent, and
      insulin non-dependent types (IDDM and NIDDM). The aim of the recent
      classification was, that different diabetic subgroups should be based on
      etiologic evidence. (Previous classification was based mainly due to the current
      therapy!). To avoid confusing nominations, the recent classification recommended
      to abandon the acronyms, IDDM and NIDDM, and only type-1 and type-2 should be
      used In the third subgroup-other diabetic groups--there are selected many
      disorders, whose etiology is mostly clear. As fourth subgroup gestational
      diabetes preserved its previous place. There are some differential-diagnostic
      problems in between type-1 and type-2 subgroups, especially between lean body
      weight type-2 and-the newly discovered latent-onset diabetes in adults (LADA).
      Diagnostic criteria of diabetes and prediabetic states are being changed
      according to epidemiological data, because type-2 patients die frequently from
      cardio-cerebrovascular fatal disorders, and elevated blood sugar values
      especially postprandially-contribute to it. Thresholds of blood sugar values for
      diagnosing diabetes are therefore decreasing, and a new category: impaired
      fasting glucose (IFG, blood sugar: 6, 1-7.0 mmol/l) was introduced. Impaired
      glucose tolerance (IGT) remained as prediabetic state. IGT + IFG are nominated as
      impaired glucoregulation. These two categories cover different populations. Oral
      glucose loading test in most problematic cases should be carried out. The
      clinical importance of postprandial hyperglycaemia (postprandial state) is
      discussed. As a new clinical concept, the Metabolic Syndrome seems to replace
      type-2 diabetes in the majority of these patients, even in the impaired glucose
      tolerance (IGT) state. Diabetics, carrying the features of this syndrome need
      holistic care.

PMID- 12501560
TI  - [Evaluation of survival in mixed connective tissue disease (MCTD)].
AB  - INTRODUCTION: 179 patients with mixed connective tissue disease (MCTD) were
      follow-up, and the cause of death was analyzed in 12 died patients. PATIENTS AND
      METHODS: The survival of 179 patients with MCTD was evaluated by using Kaplan
      Meier's method. Clinically and immunological data of the patients were analyzed
      between 1 and 25 years follow-up period (mean: 13.1 +/- 5.5 years). RESULTS: The
      five-year survival rate was 96.4%, 10-year survival rate was 93.9%, and the 15
      year survival rate was 89.6%. The cause of death was pulmonary hypertension in 5
      patients, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in 3
      cases, infection in 3 cases (hepatitis C virus induced hepatic coma in 2
      patients, Staphylococcus sepsis in one patient), and on one patient myocarditis.
      The pulmonary hypertension was the most serious prognostic factor. CONCLUSION: In
      patients with MCTD the pulmonary hypertension with endothelial cells
      proliferation and microangiopathy developed very quickly, and there was
      progressive and therapy resistant statement. The secondary virus and bacterial
      infections may develop in the patients who were followed-up the long term period.
      Their survival rate was better than the data in the literature. This fact may
      cause genetic-demographic factors, and the sequential follow-up of the patients.

PMID- 12501561
TI  - [Analysis of the stable metabolite of endothelium-derived nitric oxide of
      internal mammary artery bypass grafts at the venous drainage system of the
      recipient coronary artery. Morphologic implications and consequences].
AB  - INTRODUCTION: The internal mammary artery's endothelium continuously produces
      nitric oxide in a large quantity resulting in local and downstream
      vasodilatation, inhibition of platelet aggregation and in the tunica media
      prevents smooth muscle cell proliferation. OBJECTIVE: The aim of this study was
      to measure the concentration of the internal mammary artery bypass graft's
      endothelium derived nitric oxide's stable metabolite, (nitrite) at the venous
      drainage site (great cardiac vein) of the recipient coronary artery (left
      anterior descending), and to prove that the change of the biochemical milieu
      provides morphological stability (vasodilation and lack of atherosclerosis) in
      the recipient coronary artery based on recoronarographies. METHOD: Authors
      investigated the levels of endothelium derived nitric oxide in intraoperative
      settings of 50 off pump, partly heparinized coronary bypass surgery cases
      sampling from the internal mammary free cut end flow (81.2 +/- 12.1 mumol/l), the
      great cardiac vein (anterior interventricular vein) prior and after arterial
      bypass graft completion and in the systemic circulation (42.9 +/- 7.1 mumol/l),
      The stable metabolite concentration measurement was carried out with the modified
      Takafumi Ohta method utilizing fluoroscopy. Out of the 200 samples 164 were
      feasible to analyze. RESULTS: A significant increase was found in the great
      cardiac vein, comparing concentrations measured prior and after IMA anastomosis
      completion: 46.7 +/- 11.4 mumol/l, and 71.12 +/- 13.1 mumol/l, respectively (p <
      0.05). CONCLUSION: Based on these findings, due to the continuous protective
      (vasodilatative and antiatherogen) effect of the IMA provided EDNO, the recipient
      artery shows no pathological changes in time. This was proved by studying
      recoronarographies of 103 patients--with prior coronary bypass surgery in 5-12
      years using the IMA, and with new symptomatology. Out of 87 functioning IMA to
      LAD grafts, 85 LAD showed no atherosclerotic changes, while in the same patients'
      other coronary systems significant, de novo stenotic lesions had developed.

PMID- 12501562
TI  - [Polymyositis/scleroderma autoantibody-positive scleroderma with dermatomyositis
      (scleromyositis)].
AB  - Polymiositis/scleroderma autoantibody positive scleroderma with dermatomyositis
      connected to interstitial lung fibrosis is reported. The recently observed
      overlap syndrome is characterised by the presence of special autoantibodies, HLA
      type association and benign course. A new skin symptom (mechanic's hands) is
      described which may indicate the syndrome and one of its important internal
      manifestations, the interstitial lung disease.

PMID- 12501563
TI  - Concordance of self- and informant ratings of adults' current and childhood
      attention-deficit/hyperactivity disorder symptoms.
AB  - Self-informant rating concordance for attention-deficit/hyperactivity disorder
      (ADHD) symptoms was assessed in 281 adults at the subscale (Inattention,
      Hyperactivity-Impulsivity) and individual symptom levels. Potential demographic,
      diagnostic, and informant identity moderators were also investigated. Concordance
      levels were similar for current and childhood symptoms. Although moderate
      positive correlations were found between self- and informant ratings on both
      subscales, informants endorsed more significant inattentive symptom severity.
      Kappa coefficients were variable, suggesting low concordance for certain
      symptoms. Sex and ADHD diagnosis moderated concordance, although effect sizes
      were small. These results have implications for the use of behavior rating scales
      in diagnosing ADHD, raise questions about the validity of self- and informant
      ratings, and support the need to investigate individual-differences variables
      that may impact concordance.

PMID- 12501564
TI  - Psychopathy screening of incarcerated juveniles: a comparison of measures.
AB  - How well do brief screening measures correspond with a full-scale assessment of
      psychopathy among juvenile offenders? This study compared 3 independent screening
      measures (the Antisocial Process Screening Device [APSD] Self-Report [A. A.
      Caputo, P. J. Frick, & S. L. Brodsky, 1999], the APSD Staff Rating [P. J. Frick &
      R. D. Hare, 2001], and the Psychopathy Content Scale [D. C. Murrie & D. G.
      Cornell, 2000] on the Millon Adolescent Clinical Inventory [T. Millon, 1993])
      with the Psychopathy Checklist: Youth Version (PCL:YV; A. E. Forth, D. S. Kosson,
      & R. D. Hare, in press) in a sample of 117 incarcerated male juveniles. Modest
      correlations (.30-.49) were found between PCL:YV scores and those of the 3
      screening measures, and there was moderate accuracy (67%-82%) in identifying
      youth who scored relatively high (> or = 25) on the PCL:YV. Although these
      results support the construct of adolescent psychopathy, they indicate
      substantial limitations in the use of psychopathy screening measures with
      juvenile offenders.

PMID- 12501565
TI  - Factor structure of the Mini-Mental State Examination in adult psychiatric
      inpatients.
AB  - The factor structure of the Mini-Mental State Examination (MMSE) has been
      examined primarily in geriatric populations using differing methodology and
      yielding inconsistent results. This study examined the MMSE in 339 adult
      inpatients at a nonforensic state psychiatric hospital. Data were analyzed in the
      form of 30 dichotomous variables (1 for each scored response). A 5-factor oblique
      solution was retained, comprising factors of Orientation, Attention-Working
      Memory, Verbal Recall, Comprehension-Praxis, and Naming. Higher order factors of
      Executive Functioning and Language-Praxis were also found. The results fit the
      traditional neurocognitive domains of a mental status examination and generally
      replicated findings from the 2 largest studies published to date despite
      differences in population, suggesting that the obtained factors are fairly
      robust.

PMID- 12501566
TI  - Incremental validity of selected MMPI-A content scales in an inpatient setting.
AB  - To date, relatively few studies have been published evaluating the validity or
      incremental validity of the content scales from the adolescent version of the
      Minnesota Multiphasic Personality Inventory (MMPI-A; J. N. Butcher et al., 1992).
      A sample of 629 psychiatric inpatient adolescents who had completed the MMPI-A
      was used to evaluate the ability of selected clinical and content scales to
      predict conceptually related clinical variables. Criteria were based on clinician
      ratings, admission and discharge diagnoses, and chart reviews. Results from
      hierarchical multiple and logistic regression analyses indicated the content
      scales offered incremental validity over the clinical scales and supported the
      use of the content scales as an adjunct to the traditional clinical scales.

PMID- 12501567
TI  - Diagnostic validity statistics and the MCMI-III.
AB  - This article (a) describes and illustrates the nonredundant and clinically
      important information that may be obtained from 5 diagnostic validity statistics
      (DVSs): incremental validities of positive and negative test diagnoses, Cohen's
      kappas, Cohen's effect sizes, and areas under receiver operating characteristic
      (ROC) curves and (b) determines values of these DVSs for 24 Million Multiaxial
      Clinical Inventory III scales from results reported in 1994 and 1997 validity
      studies. The DVSs for the 1997 study (T. Millon, R. Davis, & C. Millon, 1997)
      were often more than 3 times larger than corresponding DVSs for the 1994 study
      (T. Millon, 1994). The author suggests these large differences could reflect not
      only effects of factors that caused underestimation of validities by DVSs of the
      1994 study, but also effects of factors that may have caused overestimation of
      validities by DVSs of the 1997 study.

PMID- 12501568
TI  - The observation of specific affect in marital interactions: psychometric
      properties of a coding system and a rating system.
AB  - The Specific Affect Coding System (SPAFF; J. M. Gottman & L. J. Krokoff, 1989)
      has led to conclusions about which types of dyadic affect predict positive and
      negative outcomes in marriage, yet the lack of information about collinearity
      among the codes limits interpretation of SPAFF results. Psychometric properties
      of SPAFF were examined by assessing the interactions of 172 newlywed couples with
      SPAFF and with an affect rating system developed for this study. For husbands and
      wives, factor analysis indicated 4 distinct factors of affect, representing
      anger/contempt, sadness, anxiety, and humor/affection. Anger/contempt and
      humor/affection were associated with marital satisfaction, relationship beliefs,
      and appraisals of the interactions. Correlations were in the expected directions.
      The strengths, limitations, and implications of the data are discussed.

PMID- 12501569
TI  - Assessment of quality of life in a multicultural cancer patient population.
AB  - Quality of life (QOL) is increasingly assessed in cancer patients. In this
      article, the authors examined the psychometric performance of a commonly used QOL
      questionnaire, the Quality of Life Questionnaire--Cancer 30 (QLQ-C30; N. K.
      Aaronson et al., 1993), in multiethnic cancer patients. Content validation
      studies in patients and clinicians identified possible new items. Multiple-group
      confirmatory factor analysis supported equivalent structure across ethnic groups
      (Caucasians and Asian/Pacific Islanders [APIs]). A higher order QOL factor
      appeared to directly affect functioning scales and symptom count. Exploratory
      factor analysis examined effects of new items. Ten factors were extracted, 6
      consistent with the original instrument and 4 reflecting potentially new aspects
      of QOL: Positive Social Support, Coping, Existential Well-Being, and
      Sexuality/Intimacy. The QLQ-C30 appears appropriate for use in API cancer
      patients. Further work needs to ensure that it includes all important domains.

PMID- 12501570
TI  - Development of the Multidimensional Acculturative Stress Inventory for adults of
      Mexican origin.
AB  - The Multidimensional Acculturative Stress Inventory (MASI), a 36-item stress
      measure that was developed to assess acculturative stress among persons of
      Mexican origin living in the United States, was tested on a community sample of
      174 adults (117 women, 57 men). Principal-components analyses yielded 4 stable
      and internally consistent factors: Spanish Competency Pressures (7 items),
      English Competency Pressures (7 items), Pressure to Acculturate (7 items), and
      Pressure Against Acculturation (4 items). These 4 factors accounted for 64.4% of
      the variance and correlated in the expected directions with criterion measures of
      acculturation and/or psychological adjustment. Further reliability and validity
      testing of the MASI is discussed as well as the utility of this measure in
      assessing acculturative stress among adults of Mexican origin.

PMID- 12501571
TI  - Construct validity of a measure of acculturative stress in African Americans.
AB  - The properties of the main measure of acculturative stress have not been
      systematically examined. The authors conducted a study of the construct validity
      of the Social, Attitudinal, Familial, and Environmental Acculturative Stress
      Scale (A. M. Padilla, Y. Wagatsuma, & K. J. Lindholm, 1985) in a sample of 248
      African American university students (156 of whom attended a historically Black
      college). After controlling for general life stress, the authors found that the
      relations of acculturative stress to depressive and anxious (but not suicidal)
      symptoms remained. Also, African American students at a historically Black
      college reported less acculturative stress than African American students at a
      large state university. These findings clarify the nature of a key construct and
      measure of acculturative stress.

PMID- 12501572
TI  - Screening for trauma histories, posttraumatic stress disorder (PTSD), and
      subthreshold PTSD in psychiatric outpatients.
AB  - The ability of the Structured Clinical Interview for DSM-IV (SCID) posttraumatic
      stress disorder (PTSD) module's screening question to identify individuals with
      PTSD or subthreshold PTSD was examined. First, the screen's sensitivity for
      detecting a trauma history was determined. Second, the incremental validity of a
      more thorough trauma assessment was examined by determining how many individuals
      responded negatively to the screen but then were diagnosed with PTSD or
      subthreshold PTSD. Last, the optimal SCID termination point for assessing
      subthreshold PTSD was determined. Using a trauma list increased the number of
      participants reporting a trauma; however, the SCID screen captured almost all
      individuals who had PTSD or subthreshold PTSD. When one screens for subthreshold
      PTSD, the SCID can be terminated on failure to meet Criterion B.

PMID- 12501573
TI  - The detection of feigned uncoached and coached posttraumatic stress disorder with
      the MMPI-2 in a sample of workplace accident victims.
AB  - In this study research participants completed the Minnesota Multiphasic
      Personality Inventory-2 (MMPI-2) under standard instructions and then were asked
      to fake posttraumatic stress disorder (PTSD) when completing the MMPI-2 for a 2nd
      time in 1 of 4 conditions with different instructions on how to fake PTSD: (a)
      uncoached, (b) coached about PTSD symptom information, (c) coached about MMPI-2
      validity scales, or (d) coached about both symptoms and validity scales. These
      MMPI-2 protocols were then compared with protocols of claimants with workplace
      accident-related PTSD. Participants given information about the validity scales
      were the most successful in avoiding detection as faking. The family of F scales
      (i.e., F, FB, FP), particularly FP, produced consistently high rates of positive
      and negative predictive power.

PMID- 12501574
TI  - The Obsessive-Compulsive Inventory: development and validation of a short
      version.
AB  - This article reports on the development of a revised version of the Obsessive
      Compulsive Inventory (OCI; E. B. Foa, M. J. Kozak, P. Salkovskis, M. E. Coles, &
      N. Amir, 1998), a psychometrically sound, theoretically driven, self-report
      measure. The revised OCI (OCI-R) improves on the parent version in 3 ways: It
      eliminates the redundant frequency scale, simplifies the scoring of the
      subscales, and reduces overlap across subscales. The reliability and validity of
      the OCI-R were examined in 215 patients with obsessive-compulsive disorder (OCD),
      243 patients with other anxiety disorders, and 677 nonanxious individuals. The
      OCI-R, which contains 18 items and 6 subscales, has retained excellent
      psychometric properties. The OCI-R and its subscales differentiated well between
      individuals with and without OCD. Receiver operating characteristic (ROC)
      analyses demonstrated the usefulness of the OCI-R as a diagnostic tool for
      screening patients with OCD, utilizing empirically derived cutscores.

PMID- 12501575
TI  - [Hepatitis C virus infection--after 12 years. Advances in the management of
      chronic hepatitis C].
AB  - Therapy of different manifestations of HCV infection is discussed--after 12 years
      of the discovery of HCV. In acute hepatitis C the antiviral treatment of the
      early phase is debated, but if 3 months after the onset the HCV viremia persists,
      interferon (IFN) therapy may be recommended. Asymptomatic HCV carriers with
      normal alanine aminotransferase (ALT) do not need antivirals. However, their
      serum ALT, GGT, gammaglobulin values and liver ultrasound findings should be
      monitored, to disclose an underlying liver disease, and biopsy is considered, if
      suspicion of hepatitis raises. In patients with chronic hepatitis C biopsy is
      mandatory, it may prove mild, moderate or severe histological activity (HAI).
      Moderate or severe active hepatitis C (> 2 x normal ALT, HAI > 7) should be
      treated. In the first period of the antiviral treatment for HCV, a standard IFN
      monotherapy (3 x 3 MU s.c. IFN weekly for 6-12 months) has been used, which
      resulted in 15-20% sustained response (SR) rate. In the second half of nineties,
      combination of IFN with an oral nucleoside analogue ribavirin increased the SR to
      30-30%, by means of decrease in relapse rate. Recently, pegylated IFN (PEG-IFN)
      in combination with ribavirin can lead to 60% SR. (Genotype HCV1 patients may
      show SR of about 40%, HCV 2.3 ones about 80%, respectively). Compensated HCV
      cirrhosis patients may also be treated with this type of combination, which can
      possibly inhibit progression. Decompensated cirrhosis needs liver
      transplantation. In the prevention of HCV infection, screening of blood donors,
      viral inactivation of blood products, disposable needles and education of risk
      populations are of basic importance, HCV vaccination, however is not on the
      horizon yet. Thus, antiviral treatment remains of great significance. Searches
      for new therapeutic modalities, such as multiple antiviral combinations (e.g
      amantadin + ribavirin + IFN), protease- and helicase inhibitors, ribozymes and
      cytokines may result further advances.

PMID- 12501576
TI  - [Epidemiologic surveillance of childhood leukemia in Hungary over the past 21
      years (1980-2000)].
AB  - INTRODUCTION: Investigation of trends in incidence rates of childhood
      malignancies, especially leukaemia and thyroid cancers, is essential for the
      objective assessment of health consequences of the nuclear power plant accident
      in Ukraine in 1986. AIMS: This paper reports the results of the epidemiological
      surveillance of childhood leukaemia in Hungary from 1980 to 2000, according to
      the database of the Hungarian Paediatric Cancer Registry. METHODS: All childhood
      leukaemia cases diagnosed between the period of 1 January 1980 and 31 December
      2000, age of 0-14, throughout Hungary have been recorded. The registration was
      done by the ten Paediatric Oncology Centres in Hungary. The total number of
      diagnosed and analysed cases was 1563. RESULTS: The incidence rate of childhood
      leukaemia showed a gradual, slow but significant increase of 1.2% per year over
      the observed period of time. There was neither any additional increase in the
      incidence following the accident, nor an increase in the cumulative incidence
      among the children born around the date of the accident. The accident did not
      cause a change regarding the infant leukaemia incidence in Hungary either.
      Apparent change in the geographical distribution of childhood leukaemia, which
      could be the result of the accident, was not detectable. CONCLUSION: The authors
      did not detect any change in the incidence of childhood leukaemia over the past
      21 years in Hungary, which can be attributed to the nuclear power plant accident
      in Ukraine in 1986.

PMID- 12501577
TI  - [Brain atrophy and cognitive disorder in multiple sclerosis].
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      causing severe disability via the progressive damage of white matter. Beyond
      physical signs cognitive dysfunction might be present as well. The aim of this
      study was to investigate the frequency and characteristics of brain atrophy and
      cognitive alterations. Significant cortical and subcortical atrophy was found on
      brain MRI of 30 MS patients included in this study comparing to healthy controls.
      Abnormal findings were detected in more than 60% of patients using a cognitive
      test battery. Generally, verbal abstraction, visuospatial orientation, attention,
      short-term memory was impaired and the psychomotor speed was decreased, even in
      the early stage of the disease. Depression-related complaints were found in 57%
      of this population. The Kurtzke scale, the atrophy of corpus callosum and
      widening of 3rd ventricle and Sylvian fissures were related to impaired cognitive
      performances. The authors would like to call attention to the early cognitive
      deficit and the need of treatment in MS.

PMID- 12501578
TI  - [Chronic pericarditis in Hodgkin disease].
AB  - INTRODUCTION: Among late complications of Hodgkin's disease's treatment the
      cardiovascular complications are important. The incidence of the late onset
      (later than 48 months) of chronic pericardial disease is from 11 to 50% among
      patients with Hodgkin's disease with irradiation in the past history. PURPOSE AND
      METHODS: Authors are presenting chronic constrictive pericarditis in a case among
      late consequences of therapy of Hodgkin's disease. It's difficult to observe and
      treat, because it's a rarity. RESULTS (CASE REPORT): A male patient, who is 35
      year old in the present, developed III/A2 clinical stage, mixed cellularity
      Hodgkin's disease in 1992. He got combined chemotherapy and irradiation repeated
      and he came to complete remission. In 1999 he had no symptoms, but the physical
      examination, routine chest radiography and echocardiography proved pericardial
      effusion. Apart from the most frequent reasons of pericarditis and pericardial
      effusion, radiation induced, hypothyroid and primary manifestation of Hodgkin's
      disease equally arised. After repeated fenestration of the pericardium partial
      pericardiectomy was necessary. Chronic constrictive pericarditis was proved by
      the histological evaluation of the pericardial tissue that was probably provoked
      by the mediastinal irradiation. Since the pericardiectomy he has being well, he
      had no relapsed and no signs of pericardial fluid was observed. CONCLUSIONS: The
      early recognition and treatment of late complications are possible by the help of
      the patient's follow-up. These complications of Hodgkin's disease with using of
      modern radiotherapy apparatus are usually avoided.

PMID- 12501579
TI  - [Leo Liebermann, giant in public health, was born 150 years ago].

PMID- 12501580
TI  - [The pathology of nephrosclerosis and hypertension].

PMID- 12501581
TI  - Emergency nursing: the need for clinical specialization.

PMID- 12501582
TI  - Avoiding muscular strain in patient-care activities.

PMID- 12501583
TI  - Nurses' role in illness, in relation to psychological reaction.

PMID- 12501584
TI  - Global situation of the AIDS pandemic, end 2002. Part I.

PMID- 12501585
TI  - Justice in a goldfish bowl.

PMID- 12501586
TI  - Preliminary investigation into the recovery of explosives from hair.
AB  - Sampling of hair has proved to be a useful non-invasive method for detecting
      illicit drugs. This study examined the viability of hair as a surface from which
      explosive traces can be recovered and showed that as little as one-hour vapour
      exposure can result in measurable traces of explosives. Contamination of the hair
      may result from direct contact with explosive particles or from secondary contact
      by hand. Also the paper demonstrates that hair can concentrate explosive from the
      ambient vapour of a variety of military explosives. It was found that the amount
      of TNT picked up by the hair increased with time of vapour exposure. The data
      also suggested that unwashed hair may pick up more TNT than washed hair.

PMID- 12501587
TI  - Tracking the drift of a human body in the coastal ocean using numerical
      prediction models of the oceanic, atmospheric and wave conditions.
AB  - This paper describes the use of numerical models to infer the path of a floating
      human body in the Ligurian Sea (north-west Mediterranean) during the month of
      January 2001. The prevailing oceanic currents were obtained from a state-of-the
      art real-time nowcast/forecast ocean circulation model, while the sea state was
      inferred from a numerical model of the surface gravity waves, both driven by
      regional atmospheric models. The surface currents (from the ocean model) and the
      drift ones at the ocean surface, as inferred from the wave model, were used to
      drive a Lagrangian model of the drifting body to deduce its plausible trajectory
      along the Ligurian coast. The inferred path is reasonably consistent with
      location and time of the discovery on the French coast. This note illustrates the
      utility of numerical prediction models at the disposal of modern forensic science
      in the fields of ocean sciences.

PMID- 12501588
TI  - Linking commercial burglaries by modus operandi: tests using regression and ROC
      analysis.
AB  - This paper uses statistical models to test directly the police practice of
      utilising modus operandi to link crimes to a common offender. Data from 86 solved
      commercial burglaries committed by 43 offenders are analysed using logistic
      regression analysis to identify behavioural features that reliably distinguish
      between linked and unlinked crime pairs. Receiver operating characteristic
      analysis is then used to assign each behavioural feature an overall level of
      predictive accuracy. The results indicate that certain features, in particular
      the distances between burglary locations, lead to high levels of predictive
      accuracy. This study therefore reveals some of the important consistencies in
      commercial burglary behaviour. These have theoretical value in helping to explain
      criminal activity. They also have practical value by providing the basis for a
      diagnostic tool that could be used in comparative case analysis.

PMID- 12501589
TI  - Further insights into the persistence of transferred fibres on outdoor clothes.
AB  - This study was conducted to assess persistence of fibres on items of outdoor
      clothes in normal wear situations. The persistence of acrylic and wool fibres
      transferred on 23 recipient garments was examined in relation to: time of wear;
      features of the recipient garment (fibre composition, surface structure and
      texture); conditions of wear (public transport used or not), and; their location
      on the recipient. After 8 hours of wear more than 75% of transferred fibres were
      lost during 8-10 hours of wear. After 16 hours of wear no more than 10%, most
      often up to 5%, of fibres remained. Fibres were lost at higher rate when public
      transport was used. The persistence of fibres depended more on the surface
      structure and texture of the recipient garment and the location of donor fibres
      rather than on the type of fibre.

PMID- 12501590
TI  - The sinking of the Lusitania: reviewing the evidence.
AB  - On the afternoon of 7 May 1915 the Cunard Liner Lusitania was torpedoed by a
      German U-boat whilst en route to Liverpool. Consequently in sank with the loss of
      1,195 lives. A series of investigative and formal research exercises, undertaken
      in the light of eye-witness accounts of the events surrounding that tragedy, has
      given rise to a number of hypotheses concerning the loss of this vessel. In this
      paper all the available evidence concerning the attack, and the one or more
      explosions that occurred, is summarised. The conclusions regarding the torpedo
      effects and the most likely causes of the secondary events are reported.

PMID- 12501591
TI  - Senate recesses without approving provider relief.

PMID- 12501592
TI  - FTC reiterates retrospective review of hospital mergers.

PMID- 12501593
TI  - "Drugs first" slights seniors.

PMID- 12501595
TI  - New Mountainview Regional Medical Center opens.

PMID- 12501594
TI  - Patient safety bill updates.

PMID- 12501596
TI  - [Svetlogorsk Central Military Sanatorium--a military health resort in the region
      of Western Russia].

PMID- 12501597
TI  - [Preparation of galactosyl-insulin with double saccharide density and a study of
      its hepatic targeting property].
AB  - This study was intended to improve the technical procedure so as to increase the
      saccharide density of galactosyl-recombinant insulin and elevate its liver
      targeting property. Using a branched compound 3,5-dihydroxy benzoic acid as the
      base of a conjugating bridge, the authors prepared a new double galactosyl
      recombinant insulin, whose saccharide density being two times as high as that of
      galactosyl-recombinant insulin. The double gal-insulin conjugate, gal-insulin
      conjugate and original insulin were labeled with 131I, and then the three kinds
      of 131I labeled compounds were tested in rabbit whole body imaging to measure
      their properties of liver targeting. The peak values of rabbit liver
      concentration for double gal-insulin, gal-insulin and original insulin were
      59.5%, 43.8% and 21.5%, respectively. These results demonstrate that for
      elevating the liver targeting property of galactosyl-recombinant compounds, a
      branched agent like 3,5-dihydroxyl benzoic acid can be adopted as an effective
      medium.

PMID- 12501598
TI  - [The influence of physiologic factors on the expression of striatal dopamine D2
      receptors].
AB  - The aim of this study was to know whether the strain, sex, and age-related body
      weight of rat have influence on the expression of striatal dopamine D2 receptor.
      The data on striatal dopamine D2 receptor binding 125I-IBZM in 34 rats were used
      in the comparison between pairs of groups matched on strain, sex, and body
      weight. The result showed that the strain and sex of rats had no influence on the
      striatal dopamine D2 receptor binding 125I-IBZM, but there was a body weight
      related decrease in the striatal dopamine D2 receptor binding 125I-IBZM. The
      results suggest that age-dependent decline of striatal dopamine D2 receptors is
      possible; therefore, strict age-matching is necessary to clinical studies.

PMID- 12501599
TI  - [Pharmacokinetic analysis of lactosaminated human growth hormone and human growth
      hormone].
AB  - This study was undertaken to explore and compare the pharmacokinetic features of
      lactosaminated human growth hormone(hGH-L) and human growth hormone (hGH).
      Radioimmunoassay (RIA) technique was used. After mice were intravenously injected
      with hGH-L, their blood and liver samples were collected and handled. The blood
      drug concentration and liver drug concentration were determined using RIA
      technique. Then the pharmacokinetic parameters were obtained by analysing the
      curves of blood drug concentration-time and liver drug concentration-time. hGH
      was determinated with the same methods. The results showed that the area under
      curve (AUC) of blood drug concentration-time curve of hGH-L was 32,686.90, the
      mean remain time (MRT) of hGH-L in blood was 21.37 minutes, but the AUC of blood
      drug concentration-time curve of hGH was 36,913.08 and the MRT of hGH in blood
      was 24.98 minutes. Therefore, in blood, the uptake of hGH-L was less than that of
      hGH, the removal of hGH-L was faster than the removal of hGH. In liver, for hGH
      L, the half-time of distribution (t1/2 alpha) was 1.84 minutes, the half-time of
      removal(t1/2 beta) was 11.09 minutes, the AUC of liver drug concentration-time
      curve was 17,621.9; for hGH, the t1/2 alpha was 2.11 minutes, the t1/2 beta was
      75.65 minutes, the AUC of liver drug concentration-time curve was 12,148.2.
      Therefore, in liver, the uptake of hGH-L was more than that of hGH, the
      distribution and removal of hGH-L were faster than those of hGH. Therefore, the
      pharmacokinetic features of hGH-L was better than the feature of hGH.

PMID- 12501600
TI  - [Preclinical pharmacological study of a novel myocardial perfusion agent: 99mTc
      Q3].
AB  - In order to provide an experimental foundation for clinical study, we made a
      preclinical pharmacological investigation of 99mTc-Q3, a novel myocardial
      perfusion imaging agent, technetium-99m-N,N'-ethylenebis (acetylace-toneiminato)
      bis (tris (3-methoxy-1-proply) phosphine). After the preparation of this
      compound, the kinetics of blood clearance in rabbits, biodistribution in mice,
      measurement of plasma protein binding rate, and myocardial perfusion imaging in
      dog were carried out. The labelling efficiency and radiochemical purity measured
      were over 99%, and the stability (in vitro) was good and stable up to 6 hr of
      testing at room temperature. The pharmacokinetics met the two-compartment model
      with 0.23 +/- 0.09 ml/min of excellent blood clearance, an initial half-time of
      1.5979 +/- 0.4182 min, and a late half-time of 203 +/- 25.83 min. The
      biodistribution as shown in myocardial accumulation was earlier, the radioactive
      value was higher, and once extracted, it remained relatively constant in the
      myocardium for at least 4 hr. The tracer was rapidly cleared from the blood, lung
      and the liver. The scintigraphy imaging in dog demonstrated that it was rapidly
      cleared from the lung, and the radioactive concentration approached that of
      background 1 hr after injection. At 15 min after injection, the myocardial
      imaging displayed clearly up to 3 hr. In vitro protein binding rate was low (7.13
      +/- 0.42%). The tolerance of this drug in mice was 500 times as much as in
      humans. In conclusion, 99mTc-Q3 exhibits favorable stability, biological property
      and safety, so clinical study of this preparation as a myocardial perfusion
      imaging agent is worthwhile.

PMID- 12501601
TI  - [Study on the xenoantigens of pancreatic tissues of Chinese Neijiang pig].
AB  - The expression and distribution of xenoantigens in pancreatic tissue of Neijiang
      pig were investigated with immunohistochemistry technique. BSIB4, normal human
      serum and anti-human A, B, H monoclonal antibodies were used as the primary
      antibody to examine the expression of xenoantigens in the pancreatic tissues from
      10 Neijiang pigs. The results demonstrate that compared with the negative results
      of human blood B and H type antigens, the alpha-Gal antigen was highly expressed
      on the pancreatic vascular endothelial cells and the duct epithelium. The human
      blood A type antigen was highly expressed on some islet cells, some exocrine
      secretory cells and all the duct epithelium. Since there are pre-exited
      xenoantibodies against pig pancreas cells in human serum, cross-matching test and
      graft pre-treatment are needed before clinical transplantation of pancreas. The
      expression of xenoantigens in Neijiang pig is different from other pig strains
      reported by others, which suggests that looking for a pig strain that contains
      less xenoantigens is possible.

PMID- 12501602
TI  - [Study on uptake of fluoroquinolones by Staphylococcus aureus].
AB  - This study aimed to investigate the mechanism of Staphylococcus aureus'
      resistance to fluoroquinolones. The uptake of lomefloxacin, ofloxacin by
      Staphylococcus aureus and the effect of CCCP on the uptake were studied by the
      fluorescence method. The uptake of lomefloxacin, ofloxacin by sensitive organisms
      is higher than that by resistant organisms; CCCP had different influences on
      different organisms, but no significant difference between the effects of CCCP on
      sensitive strains and on resistant strains was noted. The uptake of lomefloxacin,
      ofloxacin by SA2-16 was much lower than that by SA2-16's parent, and after the
      addition of CCCP, the uptake of both quinolones by SA2-16 increased rapidly, but
      the concentration did not reach its parent's concentration in stable condition.
      These results indicate that the decreasing of the uptake of fluoroquinolones is
      one of the mechanisms responsible for Staphylococcus aureus to resistance
      fluoroquinolones, and as a mechanism of resistance to drugs, it plays different
      roles in different strains.

PMID- 12501603
TI  - [P53 delta 37 protein exhibits 3'-5' exonuclease activity].
AB  - Mummenbrauer et al. (1996) found that P53 protein exhibits 3'-5' exonuclease
      activity. This exonuclease activity is intrinsic to wildtype P53 protein,
      dependent on Mg2+, and it can be inhibited by addition of 5 mmol/L nucleoside
      monophosphates. In the present study, we intended to know whether mutated P53
      protein--P53 delta 37 has this 3'-5' exonuclease activity or not. The results
      reveal that P53 delta 37 also has 3'-5' exonuclease activity. It has more protein
      and more exonuclease activity, but this activity can not be inhibited by guanine
      monophosphate. There are many processes related to exonuclease activity in
      mammalian cells; for example, DNA replication, DNA recombination and DNA repair.
      The exonuclease activity of P53 delta 37 protein may be important in these
      processes.

PMID- 12501604
TI  - [Study on the DNA gyrA gene mutation with resistance to fluoroquinolones in
      Staphylococcus aureus isolated from patients].
AB  - This study was aimed at the mechanism of resistance to fluoroquinolones in
      Staphylococcus aureus isolated from patients in Chengdu. The relationship between
      the point mutations in the gyrA genes and the resistance of 63 strains (57
      fluoroquinone-resistant strains and 6 wild types) isolated clinically in Chengdu
      were investigated by a combination of restriction fragment length polymorphism
      analysis. The results revealed that there are 67.27%-92.5% of the fluoroquinolone
      resistant strains against norfloxacin, fleroxacin, tosufloxacin, cipofloxacin,
      ofloxacin and sparfloxacin had a Hinf I site mutation in the gyrA genes, and most
      of such strains with such mutation in the gyrA genes showed high-level
      resistance. These indicate that Hinf site mutation in gyrA genes is the mainly
      cause of the resistance of fluoroquinolone-resistant strains of Staphylococcus
      aureus in Chengdu region.

PMID- 12501605
TI  - [PCR amplification and cloning of virulence expression regulatory gene toxR of
      Vibrio cholerae].
AB  - In order to construct a genomic bivalent oral vaccine of Leishmania donovani and
      Vibrio cholerae, we amplified a 1.3 kb DNA fragment from 7 strains of Vibrio
      cholerae with primers P1 and P2. Restriction endonuclease analysis of PCR
      amplified products from 9 strains of Vibrio cholerae was performed by digestion
      with EcoR I. The results revealed an EcoR I site in the central part of toxR
      gene. The entire toxR gene of Vibrio cholerae Non-CT strain 7743 was amplified by
      PCR with primers P1 and P2, digested with endonucleases BamH I and Hind III, then
      was orientationally cloned into plasmid pAT153. The restriction endonuclease
      analysis demonstrates that the recombinant plasmid ptR4 contains a 1.3 kb toxR
      gene fragment.

PMID- 12501606
TI  - [The change and distribution of endothelin-1 in lung of hypoxic pulmonary
      hypertension rat].
AB  - This study was aimed to determine the distribution and change of ET-1 in the lung
      of rat with chronic hypoxic pulmonary hypertension. Immunohistochemical analysis
      (Avidin-Biotion Complex) was used to localize the ET-1 immunoreactivity in the
      rat lung. The ET-1 concentration in plasma and in lung homogenate was measured by
      radioimmunoassay. In normal rats, the mean ET-1 concentration in venous plasma
      was 2.25 +/- 0.68 ng/L, in arterial plasma 1.52 +/- 0.63 ng/L and in lung 1.75 +/
      0.46 ng/L. There was no significant increase of ET-1 level in rats exposed to
      hypoxia for 2 hours, but there was significant increase of ET-1 after 24 hours
      hypoxia, and the high levels of ET-1 were maintained in the sustained hypoxia.
      There was significant correlation between the ET-1 level in arterial plasma(or in
      lung homogenate) and the maen pulmonary artery pressure. Similaryly, there was
      significant negative correlation between ET-1 in arterial plasma(or in lung
      homogenate) and PaO2. Immunohistochemical analysis revealed that the ET-1
      immunoreactivity was seen in the endothelium of pulmonary arteries, particularly
      more positive staining was seen in the band between the endothelium and the
      smooth muscle cells. Chronic hypoxia elevated the mean pulmonary arterial
      pressure, caused vessel remodelling and the right ventricular hypertrophy. These
      changes were accompained by an increase of ET-1 in plasma and lung homogenate.
      The expression and production of ET-1 were localized to endothelium and airway
      epithelium in the lungs.

PMID- 12501607
TI  - [Changes of type I collagen in the lungs of rats with hypoxic pulmonary
      hypertension].
AB  - The changes of type I collagen in the lung tissues of rats with hypoxic pulmonary
      hypertension (HPH) and its relationship to the mean pulmonary arterial pressure
      (mPAP) were investigated. The blood dynamic indexes of pulmonary circulation were
      measured by using Swan-Ganz. The distribution of type I collagen in pulmonary
      arteries, bronchi and plumonary interstitial was observed by using streptavidin
      peroxidase method (SP). The morphologic changes of small pulmonary arteries and
      the level of type I collagen were determined by image pattern analysis technique
      and gray scale scanning, respectively. The results showed, compared with the
      controls, mPAP of the hypoxic rats elevated (from 2.12 +/- 0.25 to 3.95 +/- 0.43
      kPa, P < 0.01), their small pulmonary arteries, walls thickened (MT% from 16.35
      +/- 2.64 to 35.83 +/- 3.55, MA% from 26.83 +/- 3.40 to 59.68 +/- 4.90, P < 0.01)
      and lumen narrowed. The distribution of type I collagen was mainly in the
      external layer of pulmonary arterial walls; the positive degrees of gray scale
      scanning increased and had a positive linear relationship to the mPAP and MT%.
      These findings suggest that the increase of type I collagen contents in pulmonary
      arteries is closely related to the development of HPH.

PMID- 12501608
TI  - [Effect of oxidatively modified high density lipoprotein on transcriptional
      expression of proto c-fos and PDGF receptor genes in cultured human arterial
      smooth muscle cell].
AB  - The proliferation of arterial smooth muscle cell (SMC) plays an important role in
      the process of atherosclero-genesis. Using the establishment of primary culture
      and sub-culture method for human arterial SMC, we observed the effects of native
      HDL (N-HDL) and oxidized HDL of proto c-fos and PDGF receptor genes
      transcriptional expression in cultured SMC. The results showed that N-HDL had no
      effect on the expression of proto c-fos and PDGF receptor genes in the cultured
      human SMC, that OX-HDL had no effect on the expression of PDGF receptor gene in
      the cultured human SMC, and that OX-HDL promoted the expression of protoc-fos
      gene significantly (P < 0.01). These results suggest that the OX-HDL's
      atherogenic role is closely related to its stimulating effect on proto c-fos gene
      expression of SMC.

PMID- 12501609
TI  - [Inhibition of the activation and collagen production of cultured rat hepatic
      stellate cells by antisense oligonucleotides against transforming growth factor
      beta 1].
AB  - In order to investigate whether the antisense oligonucleotides (ASON) against TGF
      beta 1 inhibit the activation and collagen production of cultured rat hepatic
      stellate cells, the authors synthesized two 20-mer phosphorothioate antisense
      oligonucleotides and their sense or missense oligonucleotides, and then treated
      the rat hepatic stellate cells (HSC) with these oligonucleotides at different
      concentrations respectively. HSC activation was assessed by the expression of
      alpha-smooth muscle actin (alpha-SMA), and TGF beta 1 level was determined by a
      standard bioassay. The production of collagen was measured by the incorporation
      of 3H-Proline into cultured rat HSCs. The results showed that the ASON against
      the translation initiation region of TGF beta 1 at a final concentration of 10
      mumol/L could inhibit the HSCs activation, the secretion of TGF beta 1 and the
      production of collagen in HSCs significantly (P < 0.05), whereas the controls
      (sense or missense oligonucleotides) had no effect at the same concentration. All
      of the oligonucleotides had no cytoxicity to HSCs. These findings suggested that
      TGF beta 1 ASON might be useful for the treatment of hepatic fibrosis.

PMID- 12501610
TI  - [Observation of the modulatiny effect of histamine on intestinal barrier
      function].
AB  - The model of CaCo2 cell monolayer system has been generally accepted as a
      standard method for in vitro study of the relationship between the epithelium and
      microbial invasion. In this study, we set up the model with a simplified method
      and used it to observe if histamine, which is an important inflammatory factor in
      gastroenteric tract, can offer some barrier protection from E. coli invasion.
      After two weeks' routine incubation, the established CaCo2 cells monolayer
      systems were co-cultured with 1 x 10(-8) mmol/L, 1 x 10(-7) mmol/L and 1 x 10(-6)
      mmol/L histamine DMEM for 2 hours, and with frank DMEM as control for the same
      length of the time. For observation on time course effect of histamine, the co
      cultures with 1 x 10(-6) mmol/L histamine DMEM were kept up for 0.5, 1.0, 2.0,
      4.0 and 18.0 hours. Bacterial invasion ws assessed by quantitating the number of
      E. coli within the coultured epithelial cells. The results showed that histamine
      significantly inhibited the invasion of E. coli to epithelial cells(P < 0.05).
      The colony counts in co-cultures with 1 x 10(-7) mmol/L and 1 x 10(-8) mmol/L
      histamine DMEM were 52.5, 30.3 and 91.3 respectively, compared with 563 in
      control group. In the study of the time course effect of histamine, the colony
      conuts of co-culture with histamine DMEM for 0.5, 1.0, 2.0, 4.0 and 18.0 hours
      were 135.5, 64.0, 29.5, 36.0 and 22.5 respectively. It was concluded that
      histamine can enhance the protective barrier function of intestinal epithelium
      against E. coli invasion.

PMID- 12501611
TI  - [Antitumor activity of the lysates prepared from anti-CD3 antibody activated
      killer cells].
AB  - This study was directed at the antitumor activity of the lysates prepared from
      CD3McAb activated killer cells. We separated the peripheral blood monocytes(PBMC)
      from normal adults. The PBMC were induced by monoclonal antibody specific for
      CD3(CD3McAb) and activated by rIL-2. The CD3McAb-activated killer cells (CD3AK)
      were smashed by ultrasonic wave, along with frozen and thawed three times, then
      the lysates were obtained by centrifugation. The lysates were tested for
      antitumor activity in vivo and in vitro. The results revealed that the inhibition
      rate of the lysates that acted on mice solid tumor hepatoma 22(H22) was 68.20%
      and the killing activity of the lysates on K562 and Raji were 83.32%, and 66.83%
      respectively. The results of this experiment suggested that the lysates prepared
      from CD3McAb-activated killer cells is one of probable agents that might apply to
      biotherapy for tumors.

PMID- 12501612
TI  - [The study on effects of human fetal liver cells on immunity of BALB/c mice].
AB  - This study sought to better understand the effects of human fetal liver
      cells(FLC) on immunity. FLC were injected into BALB/c mice intraperitoneally. The
      design included four groups: negative control and three dose (125 x 10(5), 25 x
      10(5), 5 x 10(5) FLC/day) groups. The results showed that FLC increased the
      thymus visceral coefficient, numbers of T-lymphocytes(TLC) and lymphocytes(LC) in
      blood, total number of spleen cells, the number of plaque forming cells(PFC) of
      spleen, the rate(%) of transformation and stimulus index of TLC of spleen, and
      the function of macrophages. FLC also effected the function of natural killer
      cells(NK cells) of BALB/c mice. The findings suggest that human FLC can
      strengthen the nonspecific immunity, humoral immunity and cellular immunity in
      mice. In this study, however, no effect of FLC on spleen visceral coefficient was
      noticed, and no sign of delayed type allergy was observed.

PMID- 12501613
TI  - [Adsorption behavior of chromate onto activated carbon particles].
AB  - In this paper, the adsorption behavior of chromate onto activated carbon
      particles was studied as a function of pH, flow rate and the concentration of
      tested anion. The results showed that chromate anion was not only reduced but
      also adsorbed by activated carbon particles, the percentages of reduction and
      adsorption were strongly dependent on the pH value and the flow rate. In the
      medium of pH < 10, chromate anion could be adsorbed directly onto the activated
      carbon particles and the adsorbed chromate could be eluted from activated carbon
      particles by 1 mol/L NaOH without valence change. The reduced product of chromate
      anion was mainly Cr (VI), Cr(VI) could be adsorbed in the pH > 4 medium by the
      activated carbon particles and eluted with 1%H2SO4.

PMID- 12501614
TI  - [Effect of chrysotile on nitric oxide production and anti-oxidasic activity in
      rabbit alveolar macrophages].
AB  - This study aimed to explore the role of nitric oxide (NO) and nitric oxide
      synthase (NOS) in chrysotile asbestos-caused diseases. The production of NO2-/NO3
      (the final product of NO) and the alterations of NOS, SOD and GSH-Px activity
      were investigated when rabbit alveolar macrophages (AM) were stimulated by UICC
      chrysotile. The results revealed that with the dosage elevation of UICC
      chrysotile, the rabbit alveolar macrophages showed: (1) increased mortality,
      decreased survival activity; (2) increased product of NO2-/NO3-, decreased SOD
      and GSH-Px activity; (3) increased NOS activity in the lower dosage groups, but
      decreased NOS activity in the higher dosage groups. There was significantly
      negative correlation between NO release and SOD (or GSH-Px) activity (r1 = 
      0.7125, P < 0.05; r2 = -0.8496, P < 0.05 respectively). Moreover, the
      significantly positive correlation between NO release and NOS activity was found
      in the lower dosage groups, but significantly negative correlation in the higher
      dosage groups. These findings suggest that chrysotile could induce the alveolar
      macrophages to increase NO release and to decrease SOD and GSH-Px activity, which
      may play a role in the process of asbestos-caused diseases.

PMID- 12501615
TI  - [Relationship between the alteration of 6-keto-PGF1 alpha and TXB2 in cervical
      mucus of patients with threatened preterm labor and the efficacy of magnesium
      sulfate treatment].
AB  - This study was conducted to observe the relationship between the alteration of 6
      keto-PGF 1 alpha and TXB2 in cervical mucus of patients with threatened preterm
      labor and the efficacy of magnesium sulfate treatment, and to examine whether
      they could act as markers of efficacy and prognosis in treatment of preterm
      labor. Cervical mucus was collected from 28 patients with threatened preterm
      labor before and after magnesium sulfate treatment, the levels of 6-keto-PGF1
      alpha and TXB2 were determined by radioimmunoassay (RIA). The results showed that
      the levels of 6-keto-PGF1 alpha and TXB2 decreased in patients successfully
      treated with magnesium sulfate (P < 0.01), and the ratio of 6-keto-PGF1 alpha to
      TXB2 increased significantly (P < 0.001). The levels of 6-keto-PGF1 alpha and
      TXB2 increased in patients with failed magnesium sulfate treatment (P < 0.01),
      and the relevant ratio decreased significantly (P < 0.001). The results indicate
      that the levels of 6-keto-PGF1 alpha and TXB2 in the cervical mucus of patients
      with threatened preterm labor may change significantly before and after magnesium
      sulfate treatment and they could be used as markers of efficacy and prognosis in
      treatment of preterm labor.

PMID- 12501616
TI  - [Effects of Nilestriol on reproductive system in ovariectomized rats].
AB  - The purpose of this study was to determine the effects of Nilestriol on
      reproductive system. Female SD rats, aged 4 months, were randomly divided into
      three groups. The OVX group's rats were subjected to bilateral ovariectomy, the
      SHAM group's rats received sham surgery; the Nilestriol(CEE3) group's rats were
      subjected to bilateral ovariectomy and treated with CEE3(0.15 mg/100 g BW, once a
      week). A computerized image analyzer was used to evaluate the endometrial
      pathological changes 10 weeks later. The weight of uterus was measured. The
      results showed that in OVX group, atrophic uteri; and atrophied endometria were
      noted. The weight of uterus was increased in CEE3 group, compared with that in
      OVX group (642.20 +/- 283.60 mg vs. 297.00 +/- 106.90 mg, P < 0.05). The volume
      fraction of endometrial glands was also significantly elevated in CEE3 group,
      compared with that in OVX group (1.84% vs 0.58%). The endometria in CEE3 group
      were at an early proliferative stage. These suggest that Nilestriol has a slight
      stimulating effect on the uteri of ovariectomized rats, including their
      endometria and uterine smooth muscles. Nilestriol is suited to be used in
      combination with progestogen.

PMID- 12501617
TI  - [Tangent time constant and wave-speed mechanism of F-V curve configuration in
      smokers and clinical significance].
AB  - This study was conducted to explore the mechanical mechanism of the formation of
      F-V curve configuration with tangent time constant (tau 1) and wave-speed theory
      for smokers. F-V curves were measured on 22 passive smokers and 94 active ones.
      FVC, V75, V50 and V25 were obtained, and tangent time constants at high, mid, low
      lung volumes, tau t75, tau t50 and tau t25 were calculated, and analysed with
      wave-speed theory. The results showed that the chief changes taking place only in
      heavy smokers and convex type of F-V curve were: decreased V50 and V25; tau t25 >
      or = 1s; tau t75-tau t50 < tau t25 in "trumpet fashion" change; and tau t75 < tau
      t50 < tau t25 in "tower fashion" change. Then, tau t25 > or = 1s, tau t75-tau t50
      < tau t25 and tau t75 < tau t50 < tau t25 were assigned as three tau t characters
      of smoking effect. They led to an increased convexity of the convex type of F-V
      curve, and reflected the decrease of small airway functions. Similar to the
      decrease of V50 and V25, they have important significance in assessing small
      airway functions and thus merit clinical use.

PMID- 12501618
TI  - [Experiment study on fit of anterior osseointegrated implant frameworks related
      to the number of fixture abutments].
AB  - Good fitness of osseointegrated frameworks was a key factor to protect implant
      for function. The purpose of this study was to evaluate the fitness of anterior
      implant fixed bridge in one-piece casting made of Ni-Cr alloy in different
      numbers of fixture abutments. The specimens were measured by the three
      dimensional measurement system (German Opton uMM550). The results demonstrated
      that there were statistically significant differences in dimensional changes
      among one, two or three fixture numbers, the space of retention was 50-150
      microns, and the flow of retention was 100-250 microns.

PMID- 12501619
TI  - [A study on the changes of blood levels of type III procollagen and type IV
      collagen in relation to artery blood gas and lung function in patients with cor
      pulmonale].
AB  - This study was conducted to explore the changes of PC III (type III procollagen)
      and C IV (type IV collagen) in the serum in patients with chronic pulmonary heart
      diseases. The blood levels of PC III and C IV in 25 patients with chronic
      pulmonary heart diseases and 20 normal subjects were measured by radioimmunoassay
      and were analysed in relation with the artery blood gas and pulmonary function
      parameters. The results revealed that the blood levels of PC III and C IV in the
      patients were significantly higher than those in normal subjects, and were
      negatively correlated with PaO2, FEV1%, MBC and MMEF (P < 0.05, P < 0.01). The
      results suggest that the blood levels of PC III and C IV of patients with chronic
      pulmonary heart diseases are significantly increased and significantly correlated
      with pulmonary function damage and hypoxia.

PMID- 12501620
TI  - [The effect of heparin on mesangial cells proliferation and cytokines
      production].
AB  - The human glomerular mesangial cells(MC) proliferation and cytokines secretion
      were detected by using MTT method and biological active method so as to assess
      the effects of heparin on the cultured human glomerular MC induced by
      lipopolysaccharides (LPS). The results showed that there were basic production of
      interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-alpha) on MC in the
      control group without LPS, that high-concentration heparin(500 U/ml) increased
      the effects of LPS on MC, and that low-concentration heparin (5 U/ml) conversely
      inhibited the effects of LPS on MC. These data indicate that the low
      concentration heparin could inhibit the proliferation of MC and the secrection of
      IL-6 and TNF-alpha induced by LPS, and hence provide an experimental evidence for
      administration of heparin in the treatment glomerular disease.

PMID- 12501621
TI  - [The relationship of brainstem auditory evoked potential to cerebral blood flow
      volume in with vertebrobasilar transient ischemic vertigo].
AB  - This study was aimed at the relationship of brain-stem auditory evoked
      potential(BAEP) with cerebral blood flow(CBF) volume and vascular pathological
      changes in patients with vertebro-basilar transient ischemic vertigo (VBTIV). 65
      patients were examined by magnetic resonance angiography(MRA), transcranial
      Dopplar(TCD) and BAEP; 26 controls were examined by MRA and TCD. In the patient
      group, MRA showed that vascular pathological changes were obvious in 50 patients,
      and obscure or absent in 15 patients. The CBF volume [112.3-278.9 ml/min (2s)] of
      control group was higher than that (48.0-262.0 ml/min) of the patients group (t =
      2.43, P < 0.01) in which 15 patients had low CBF volume and 50 patients had
      normal CBF volume. The BAEP of 47(72.3%) patients was abnormal. Out of 15
      patients with low CBF volume, 14(93.3%) had abnormal BAEP, but out of 50 patients
      with normal CBF volume, only 33(66%) patients had abnormal BAED (chi 2 = 4.34, P
      < 0.05). In the 50 patients with obscure obvious vascular pathological changes,
      40(80%) patients had abnormal BAEP, but in the 15 patients with obscure or
      without the changes, only 7(43.3%) patients had abnormal BAEP (chi 2 = 4.86, P <
      0.05). These results suggested that there might be a close relationship of BAEP
      with CBF volume and vascular pathological changes.

PMID- 12501622
TI  - [Detection and activity analysis of gelatinases in bone and soft tissue tumors].
AB  - This study was aimed to investigate the expression of gelatinases (MMP-2 and MMP
      9) in mesenchymal tumors and the roles they act during invasion and metastasis.
      45 cases of bone and soft tissue tumors with various pathologic categories were
      subjected to immunohistochemistry and gelatin zymography analysis. The results
      showed that the positive immuno-staining ratio and the activity of both MMP-2 and
      MMP-9 were higher in malignant tumors than in benign tumors and normal tissue. In
      malignant tumors, the positive stained cells usually gathered in the marginal
      area of tumor foci or the invading area, or formed distinctive positive-stained
      cell clusters, indicating their relationship with the aggressive biologic
      behavior of this kind of malignant tumor.

PMID- 12501623
TI  - [Comparison of efficiency and merits of two parameters for bronchial challenge
      test by use of a simple equation].
AB  - The aim of this study was to investigate the relationship, merit and weakness of
      two parameters--the FEV1 and sGaw--for bronchial challenge test. The 36 cases of
      asthma patients were subjected to bronchial challenge test with FEV1 and sGaw as
      the test parameters simultaneously. A simple calculative equation was used. The
      Mch (challenge medicine) concentrations for a 20% decrease of FEV1(PC20FEV1) and
      for a 35% decrease of sGaw (PC35 sGaw) were figured out. The results showed that
      PC20 FEV1 and PC35 sGaw were 2.73 +/- 2.92 g/L and 1.50 +/- 2.03 g/L
      respectively. A significant difference between them was noted (P < 0.05), and
      their coefficient of correlation r = 0.738. The linear regression equation was
      PC35sGaw = 0.100 + 0.513 x PC20 FEV1. PC35sGaw was obviously lower than PC20
      FEV1; the Mch amount for PC35sGaw was almost one half of that for PC20 FEV1,
      which indicated that sGaw was more sensitive than FEV1 as a parameter for
      bronchial challenge test. The FEV1, however, needs a relatively low standard of
      instrument, so it is more obtainable and popularized.

PMID- 12501624
TI  - [Re-evaluation of proteinuria and qualitive methods for diagnosis of diabetic
      nephropathy].
AB  - This study was aimed to re-evaluate the proteinuria quantitative and qualitative
      methods for diagnosis of diabetic nephropathy (DN). 136 cases were divided into
      two groups of proteinuria negativeness and postiveness by the results of urine
      routine examination. The clinical and biochemical indices and the frequencies of
      other diabetic complications of the two groups were compared. The results showed
      that the blood glucose and glycated Hb in the two groups were increased,
      especially in the proteinuria negative group (P < 0.01 and 0.05, respectively).
      There was a high prevalence of hypertension and other diabetic complications in
      the two groups, and it was higher in the positive group than in the negative
      group (P < 0.05 and 0.01, respectively). The frequencies of hyperlipoproteinemia
      in the two groups were over 40%, but no significant defference was observed
      between them (P > 0.05). There was correlation between hypertension and
      proteinuria (P < 0.01) but no correlation between diabetic retinopathy and
      proteinuria. The prevalence of azotemia in the proteinuria negative group was
      17.07%. These suggest that the amount of proteinuria can not completely reflect
      the duration and severity of DN. Negative proteinuria in routine examination
      cannot rule out DN. For diagnosis of DN, it is necessary to think about all data
      on blood glucose, blood lipid, blood pressure and the change in fundus oculi.

PMID- 12501625
TI  - [The effect of cardiopulmonary bypass on expression of myocardial nitric oxide
      synthase in patients for valve replacement].
AB  - The objective of this study was to assess the effect of cardiopulmonary bypass
      (CPB) on expression of nitric oxide synthase (NOS) in patients for valve
      replacement. Ten adult patients were included in this study. CPB was initiated
      with a bubble oxygenator, aorta was clamped, and cold crystalliod cardioplegia
      was delivered into the aortic root. The myocardium of atrial appendage was
      obtained pre-CPB and 45 minutes post-CPB. The expression of three kinds of NOS
      isoenzymes was assessed by immunohistochemistry and microcomputerized image
      analysis. The results demonstrate that there are expression of nNOS (nervous
      NOS), iNOS (inducible NOS) and eNOS (endothelial NOS) in the atrial myocardium of
      patients for valve replacement. Compared with the expressions of NOS pre-CPB, the
      post-CPB expression of nNOS increased and that of eNOS decreased (P < 0.05), but
      no significant change in expression of iNOS was noted(P > 0.5). We belive that
      the decreased expression of eNOS may be related with the deficiency of nitric
      oxide release and may be responsible for tissue damage during CPB.

PMID- 12501626
TI  - [The lymphocyte subset and blood interleukin-2 level in children with Henoch
      Schonlein purpura before and after cimetidine treatment].
AB  - The objective of this study was to evaluate the effect of cimetidine treatment on
      cellular immunity in children with Henoch-Schonlein purpura. T cell subset was
      detected by double marker flow cytometry and the level of IL-2 in peripheral
      blood was measured by MTT method, before and after cimetidine treatment. The
      results showed that CD3+, CD4+ T cell subset, CD4+/CD8+ ratio, and blood IL-2
      level increased after the treatment (P < 0.05). There was no significant change
      in CD8+ T subset after the treatment. These findings indicate that cimetidine can
      promote T lymphocyte proliferation and differentiation, especially TH1 lymphocyte
      activity.

PMID- 12501627
TI  - [Effects of homoharringtonine on proliferation of human retro-ocular
      fibroblasts].
AB  - This is a study amied at the effects of homoharringtonine on the proliferation of
      human retro-ocular fibroblasts. The human retroocular fibroblasts (HROFb) were
      cultured and MTT colorimetry assay was used to determine the proliferation of
      HROFb. The influence of homoharringtonine on the proliferation of HROFb was
      observed in vitro. The results showed that MTT colorimetry assay could precisely
      reflect the proliferation of HROFb. The absorbance was directly proportional to
      the number of the cells (r = 0.996, P < 0.001). The proliferation of HROFb was
      inhibited by the homoharringtonine and the cell proliferation percentage was
      correlated positively to the homoharringtonine level (r = 0.6932, P < 0.001).

PMID- 12501628
TI  - [Study of estrogen and progesterone receptors in endometrial carcinoma].
AB  - This study was conducted to immunohistochemical and biochemical measurements of
      estrogen receptor (ER) and progesterone receptor (PR) in endometrial carcinoma
      and elucidate the relationship between ER/PR contents and the clinico-pathologic
      features. Specific monoclonal antibodies to human ER and PR were used and the
      immunohistochemical (IHC) assay was performed on 36 specimens of endometrial
      carcinomas. Twenty-eight out of 36 specimens' ER and PR contents were also
      measured by dextran-coated charcoal analysis (DCC). ER and PR positive rates were
      44.4% and 52.8% by IHC, and 50% and 57.1% by DCC, respectively. The two methods
      correlated significantly, the correlation coefficient between DCC and IHC being
      0.565 for ER and 0.563 for PR (P < 0.05). ER and PR contents were much lower in
      grade 3 than in grades 1 and 2 endometrial carcinomas (P < 0.01). The authors
      conclude that the levels of ER and PR are associated with the differentiation of
      endometrial carcinoma. The immunohistochemical and biochemical methods correlate
      well. A combination of the two methods may be more useful in predicting the
      prognosis and choosing the treatment.

PMID- 12501629
TI  - [Influence of the administrators of family planning on the spread of norplant in
      countryside of Sichuan].
AB  - The purpose of the study was to understand the family planning administrators'
      knowledge of Norplant and their fluence on the spread of Norplant in countryside
      of Sichuan. 156 administratoras were surveyed. It was found that most of the
      administrators worked hard on education, propagation, organization and management
      of using Norplant, and they recognized the contraceptive efficacy of Norplant.
      However, the educational level of the administrators was generally low. They were
      short of the training on Norplant related knowledge(training rate was only
      36.5%). The degree of the users' satisfaction and the administrators' knowledge
      on Norplant varied between areas. The result indicated that the basic quality of
      the administrators and their knowledge of Norplant were influences on the spread
      of Norplant in the countryside of Sichuan. Soit is very important to improve the
      basic quality and knowledge of the administrators of family planning.

PMID- 12501630
TI  - [Cell cycle analysis and pathological changes of malignant tumors treated with
      electrochemical therapy].
AB  - To investigate the mechanism and to observe the effectiveness of electrochemical
      therapy(ECT), 33 patients of late stage cancers which treated by ECT were
      included in this study. Flow cytometry (FCM) and pathology were used to observe
      the changes of tumor cells before and after ECT. Tumor cells of G1, G2/M, S
      phases and aneuploid cells were found to be killed almostly and the ratio of
      apoptosis was elevated greatly after ECT. Also, pathological evidence proved the
      death of tumor cells and some characters of apoptosis. So, ECT can non
      selectively kill tumor cells and induce the apoptosis of them, and FCM was a way
      to evaluate the effectiveness of ECT.

PMID- 12501631
TI  - [Evaluation of modified maze procedure by Doppler tissue imager].
AB  - Since 1998 the cardiac surgeons of WCUMS have performed modified maze procedure
      for treating the patients with rheumatic mitral valve disease accompanied with
      chronic atrial fibrillation (Af). In this study, echocardiography, especially
      Doppler Tissue Imager (DTI), was used to evaluate atria contraction and function
      of such patients before and after the operation. 14 rheumatic mitral disease
      patients, aged 27-60 years, were chosen; among them, 11 had mitral stenosis, 3
      mitral regurgitation. The control group consisted of 16 cases, aged 24-67 years,
      with normal echocardiogram. Before and half-1 year after the operation, left
      atrium, left ventricle, right atrium and ventricle were measured, and cardiac
      function and posterior wall motion of left atrium were measured. Velocity of
      mitral valve annual and tricuspid valve annual was measured in DTI. The results
      showed: There was no age difference between the two groups. The motion of
      posterior wall of left atrium was 4.18 +/- 0.37 mm in the operation group, 4.09
      +/- 0.29 mm in the control group (P > 0.05). No difference in velocity of
      mitral/tricuspid valve annual between the two groups was observed; 3 peaks of
      mitral valve annual were S 0.11 +/- 0.02, e 0.11 +/- 0.01, a 0.09 +/- 0.01 (m/s)
      in operation group, and S 0.08 +/- 0.00, e 0.10 +/- 0.01, a 0.08 +/- 0.01 (m/s)
      in control group, (P > 0.05, respectively); 3 peaks of tricuspid valve annual
      were S 0.10 +/- 0.01 vs 0.11 +/- 0.08, e 0.11 +/- 0.08 vs 0.10 +/- 0.01, a 0.10
      +/- 0.10 vs 0.09 +/- 0.01 (m/s), (P > 0.05, respectively). The diameter of left
      atrium after operation in cases of mitral stenosis decreased significantly,
      compared with that before operation (P < 0.01). The diameter of right atrium
      after operation decreased significantly, compared with that before operation (P <
      0.01). There was no significant change in right ventricle/left ventricle/EF and
      FS. The diameter of left atrium after operation in cases of mitral regurgitation
      decreased significantly, compared with that before operation (P < 0.01). The
      diameter of left ventricle after operation decreased significantly, compared with
      that before operation (P < 0.05). No significant change in right ventricle/right
      atrium/EF and FS was noted. The authors conclude the DTI, as a new diagnostic
      method in echocardiography, has high sensitivity and is less influenced when used
      to observe motion of atrium-ventricle annual influenced. It can avoid the error
      caused by deviation of blood displacement. In the rheumatic mitral valve disease
      patients who had mitral valve replacement and modified maze procedure, atrial
      contraction respores, the risk of thromboembolism decreases and prognosis
      improves. So the operation is worth doing.

PMID- 12501632
TI  - [Factor analysis on the intelligence of patients with schizophrenia].
AB  - The authors made a factor analysis on the intelligence of patients with
      schizophrenia. 119 patients with schizophrenia were measured by Wechsler Adult
      Intelligence Scale-Revised China (WAIS-RC). The results revealed the average full
      intelligence quotient (IQ) of schizophrenia was 79.70, the verbal intelligence
      quotient(VIQ) 84.43, and the performance intelligence quotient(PIQ) 74.10.
      Multiple regression showed the regression coefficient of educational level for IQ
      was 8.6721. The regression coefficient of the course of disease for IQ was
      negative 0.1519. Factor analysis showed that the cumulative percent of three
      factor solution of schizophrenia was 73.5. In conclusion, the IQ of most patients
      with schizophrenia was lower than norm, VIQ > PIQ(P = 0.0000). Educational level
      had greater influence on IQ. The longer the course of disease was, the worse the
      intelligence came to be. Factor analysis indicated that three-factor solution of
      schizophrenia was similar to that of norm, but each subtest value was lower than
      norm.

PMID- 12501633
TI  - [A modified assay for phospholipids in blood serum].
AB  - An antiscorbutate reduction method for serum phospholipids assay was modified by
      decreasing the consumed quantity of sulphuric acid and perchloric acid to 30% of
      that before modification, and the quantity of serum to 40% of that before
      modification. The digesting time was only 50%-62% of that before modification.
      The coefficients of variation (CV) were 3.4% and 3.7% for two batches of assays.
      Recovery of phosphotidylcholine added to serum ranged form 94% to 109%, averagely
      100.8%. Serum phospholipids assay of 50 normal adults by the methods before and
      after modification showed statistically no significant difference (2.813 +/-
      0.333 mmol/L vs 2.828 +/- 0.316 mmol/L, P > 0.05), but good correlation (r =
      0.991). The results indicate that the modified assay for serum phospholipids can
      decrease the use of serum and reagents, especially the harmful acids, and get the
      same result as that before modification.

PMID- 12501634
TI  - [Isolation and phenotypic analysis of lamina propria mononuclear cells from
      colonoscopic biopsy specimens].
AB  - This study was directed to the method of isolation of lamina propria mononuclear
      cells (LPMC) from mucosal biopsy specimens and the phenotypic analysis of the
      cells. Ten biopsy specimens, taken individually from 8 patients with ulcerative
      colitis (UC), 5 normal controls and 22 patients with colorectal cancer, were
      collected to compare the factors that influence isolation and cell yield and to
      analyze the lymphocyte subsets by means of two-color flow cytometry. LPMC yield
      averaged 10(6) with a viability of more than 95% in UC, twice the yields in other
      two groups. The percentages of total T, B cells in three groups were similar (P >
      0.05). When the UC group was compared with the other two groups, a significantly
      higher proportion of CD3(+)-CD4(+)-T cell (49.98% vs 37.54% and 37.25%, P < 0.01)
      was noted, whereas a lower proportion of CD3(+)-CD8(+)-T cell (23.64% vs 31.52%
      and 31.07%, P < 0.01) was observed. These data showed that the yield and
      viability of LPMC isolated from biopsy specimens were good enough for a
      phenotypic or functional analysis, which might be helpful to mucosal immune
      research on gut disorders, such as UC.

PMID- 12501635
TI  - [GnRH receptor and the regulation of its gene expression].
AB  - The function of GnRH(gonadotropin-releasing hormone, LHRH) is mediated by GnRH
      receptor (GnRHR). The study on GnRHR is one of the highlights in
      neuroendocrinology and reproductive biology. The latest study of GnRHR, including
      molecular structure of GnRHR, regulation of GnRHR gene expression, distribution
      of GnRHR, the regulation of GnRHR by peptide and steroid hormone, as well as
      signal transduction mediated by GnRHR, are reviewed in the present article.
      Studies on GnRHR will make great contribution to the understanding of the
      regulation of reproduction and its action for therapy of malignant tumor.

PMID- 12501636
TI  - [Progress on the study of neurochemical mechanisms of learning and memory].
AB  - Brain function research is one of the most important projects in biological
      sciences. Learning and memory is one of the most advanced functions in brain.
      This article reviewed the effects of some neurotransmitters and neuroactive
      peptides on learning and memory in an attempt to stimulate the research aiming at
      improving learning and memory.

PMID- 12501637
TI  - [Vestibular compensation: a privileged model for the study on plasticity of
      central nervous system].
AB  - Vestibular compensation is now considered as a privileged model for the study of
      the underlying mechanisms of restitution and substitution of functions after
      nervous system lesions. This model is ubiquitously suited for the research of
      plasticity of central nervous system and recuperation of functions. This review
      focuses on the latest progress of the research on vestibular compensation in the
      aspects of electrophysiology, biochemistry and molecular neurobiology as well as
      the expression of growth-associated protein (GAP-43), and the pharmacological
      effects of extract of Ginkgo biloba(EGb 761) during the course of vestibular
      compensation are specially discussed.

PMID- 12501638
TI  - [Research progress on regulation of vascular endothelial barrier function].
AB  - The regulatory mechanisms of vascular endothelial barrier function are
      complicated. Inflammatory mediators, such as alpha-thrombin, activate
      phospholipases to mediate generation of IP3 and other second messengers through
      receptor-coupled G protein. Protein kinase C and myosin light chain kinase are
      then activated, leading to phosphorylation of myosin light chains, rearrangement
      of F-actin skeleton, interendothelial cell gap formation and increased
      endothelial permeability.

PMID- 12501639
TI  - [Research advances on fusion peptide and mechanisms about virus penetration into
      membrane].
AB  - The first step of viral infection is virus fusion with target membrane. The
      process is induced by fusion peptide located in glycoprotein on virus membrane.
      Fusion peptide exploited after interaction with receptors and penetrates into
      target cells membrane. Lipid molecules surrounding peptides are rearranged and
      membrane fusion occurs through the formation of a intermediate state. This review
      introduces the research advances of viral fusion peptides and its mechanism of
      penetrating into membrane.

PMID- 12501640
TI  - [Recent advances of heterologous gene expression in E. coli].
AB  - In recent years, along with the rapid development of genetic engineering
      technologies, a vast amount of valuable proteins have been expressed in E. coli
      with high productivity. The problems concerning the productivity and purity of
      the heterologous proteins are no longer the major ones, as many expression system
      and protein purification schemes have been developed and perfected. More
      attention is being payed to the activity, specific activity, correct folding and
      intactness of the heterologous proteins. Perhaps it is the solutions to such
      problems that will finally lead to the maturity of the application of recombinant
      proteins.

PMID- 12501641
TI  - [Involvement of habenula nucleus in the pathogenesis of stress induced
      hypertension and the underlying mechanisms].
AB  - Stress-induced hypertension (SIH) was performed by electric shock on hind paw in
      rats. Habenula(Hb) lesion decreased the degree of SIH. After stress, the Ang II
      concentration in blood plasma and in Hb were increased. BP was elevated after icv
      or MHb administration of Ang II, and decreased after microinjection of saralasin
      into MHb. The BP changes induced by Ang II and saralasin were more prominent in
      SIH than in normotensive rats. Iontophoresis of AngII (or saralasin) into Hb
      increased (or decreased) the discharges of the excitatory neurons related to
      cardiovascular activity. Ang II could inhibit the activity of Ik channel. Using
      the same methods, the actions of L-NNA and SNP were investigated. From above, it
      is suggested that Hb is involved in the development of SIH. Stress stimulus
      strengthened the sensitivity of Hb, especially MHb to AngII, and also induced in
      increase of AngII. These changes would promote the response of sensitized Hb in
      the development of SIH.

PMID- 12501642
TI  - [Studies on inhibition of human lung carcinogenesis in early stage by oltipraz
      and its effects on some gene expression and regulation].
AB  - By using human fetal lung (HFL) as experimental material, the inhibition of HFL
      carcinogenesis in early stage by oltipraz and its molecular mechanisms were
      studied. The results showed that oltipraz is effective in the inhibition of
      carcinogenesis prior to or at the same time with Cigarette Smoking
      Condensate(CSC) treatment; oltipraz can decrease GSTs activity and GST-pi protein
      content along with its inhibition of HFL carcinogenesis; oltipraz can decrease
      mp53 expression; oltipraz can prevent but can not reverse the ras gene mutation;
      oltipraz can induce apoptosis of GLC cell obviously in a dosage of 120
      micrograms/ml. Meanwhile, it is related to high expression of c-fos and low
      expression of GST-pi in apoptosis; oltipraz may affect c-fos gene expression
      through induction of a protein factor which links with DSE.

PMID- 12501643
TI  - [Ionic channel pathies].

PMID- 12501644
TI  - [Capacitation and its sequelae].

PMID- 12501645
TI  - [The nucleus is endowed with special calcium transport system].

PMID- 12501646
TI  - [Mechanism of IGF1 receptor activation and signal transduction specificity].

PMID- 12501647
TI  - [The relation between immunoinflammatory reactions and Alzheimer's disease].

PMID- 12501648
TI  - [Nuclear matrix and regulation of gene expression].

PMID- 12501649
TI  - [Correlation of nitric oxide and gastric ulcer].

PMID- 12501650
TI  - [Is nitric oxide convulsant or anticonvulsant?].

PMID- 12501651
TI  - [Calcium activated neutral protease and its endogenous inhibitor].

PMID- 12501652
TI  - [Role of ventrolateral medullary areas in depressor reflex].

PMID- 12501653
TI  - [Methods for isolation of microvascular endothelial cells].

PMID- 12501654
TI  - [Melatonin: a multiple function photoperiodic signal].

PMID- 12501655
TI  - [Biology at the turn of the century].

PMID- 12501656
TI  - [Mechanisms underlying opioid addiction: new progress].
AB  - The mechanisms of opioid addiction has attracted much attention of researchers
      around the world. In the present review, we have discussed the recent progress in
      the following topics. (1) Neurotransmitters participating the mechanism of opioid
      addiction; (2) Roles of different opioid receptors in opioid addiction; (3)
      Possible involvement of learning and memory in opioid addiction; (4) The
      intracellular signal transductive pathways after the activation of opioid
      receptors. Possible method of prevention and treatment of opioid addiction are
      also discussed.

PMID- 12501657
TI  - [11 beta-Hydroxysteroid dehydrogenase].
AB  - There are two types of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 11
      beta-HSD 1 is an oxoreductase interconverting biologically active cortisol and
      inactive cortisone. 11 beta-HSD 2 is an exclusive oxidase only converting
      cortisol to cortisone. It has been recognized that 11 beta-HSD 2 confers the
      specificity of mineralocorticoid receptor in the kidney and protects the fetus
      from high levels of maternal glucocorticoids in the placenta. Lack or malfunction
      of this enzyme could result in the development of apparent mineralocorticoid
      excess syndrome and intrauterine growth retardation of the fetus. 11 beta-HSD is
      possibly involved in a number of other physiological and pathological conditions
      such as stress, hypertension, diabetes mellitus and neurodegenerative disorders.
      The functions of 11 beta-HSD 1 are not very well understood.

PMID- 12501658
TI  - [Study on the molecular structure and function of protein kinase C isoenzyme].
AB  - Protein kinase C (PKC) is a serine/threonine kinase family consisting at least 11
      related isoenzymes, and it can be divided into four distinct classes,
      conventional PKC (cPKCs), novel or new PKC (nPKCs), atypical PKC (aPKCs), and PKC
      u. All PKC members contain conserved and variant amino acid sequences in ATP
      binding sites, phosporyl transfer region, pseudosubstrate region, and phorbol
      ester binding sites. PKC isoenzymes exhibit distinct tissue distribution and play
      a critical role in cellular events. This review mainly summarized the PKC effects
      on tumorigenesis, tumor invasion and metastasis, tumor multidrug resistance,
      differentiation and development of hematopoietic progenitor cells, and hormonal
      production and secretion.

PMID- 12501659
TI  - [The development of endothelial cell-to-cell junctions].
AB  - The endothelium forms the main barrier to the passage of macromolecules and
      circulating cells from blood to tissues. Endothelial permeability is in large
      part regulated by intercellular junction. The article here dicusses the
      development of endothelial cell-to-cell junction. The types of endothelial
      junctions, transduction, regulation of changes of endothelial cell-to-cell
      junction, the effects of the flow in vasculature and the leukocytic extravasation
      have been discussed. It was emphasized that the changes of endothelial junctions
      and skeleton were important in regulating endothelial permeability, leukocyte
      extravasation and reorganization of vascular endothelial cell-to-cell junction.

PMID- 12501660
TI  - [19FNMR in biomedical research].
AB  - Nuclear magnetic resonance(NMR) is a noninvasive method which can be directly
      used to study biological samples in vivo and in vitro. The information that can
      be obtained is on the molecular level. The high intrinsic sensitivity of 19F for
      detection and lack of significant 19F background make 19FNMR studies an
      attractive strategy by introducing fluorinated indicators for in vivo studies.
      19FNMR has been used to study many physiological and biochemical indexes
      including metabolism of drugs containing fluorine, intracellular free ions such
      as Ca2+ and Mg2+, intracellular pH, oxygen concentration or oxygen tension(pO2),
      membrane potential, tissue temperature, blood volume and cell volume and so on.

PMID- 12501661
TI  - [Research progress in brain-specific metallothionein-III].
AB  - Metallothionein-III (MT-III) is a low molecular weight protein characterized by
      its abundant content of cysteins. It is predominantly expressed in the zinc
      containing neurons and associated with the development of brain. MT-III inhibits
      the survival and neurite formation of the cultured neurons in vitro. It has
      comparatively specific affinity for zinc, thus may regulate the zinc-dependent
      biological processes. Studies demonstrating that MT-III is down-regulated in
      Alzheimer's disease and that MT-III "knockout" mice appear highly sensitive to
      kainate-induced seizures suggest that it may play important roles in some
      degenerative diseases of the brain.

PMID- 12501662
TI  - [Immunoregulatory actions of melatonin microinjected into hippocampus in rats and
      their mechanisms of action].
AB  - This paper reports that melatonin(MT) microinjected into hippocampus (ih)
      produces immunoregulatory actions. In ih MT rats, the contents of norepinephrine
      (NE) were increased in the hippocampus, and the immunologic effects of the ih MT
      could be related to alpha 2 adrenergic receptors of sympathatic systems. It was
      also found that MT could be produced by the splenocytes where the two key enzymes
      (NAT, HIMOT) exist. The immunoregulatory actions of ih MT could be related to the
      increased production of MT in the splenocytes, which induced the release of beta
      Endorphin. The increased NE in the hippocampus in ih MT rats, could inhibit the
      release of MT in pineal gland and the actions may also be mediated through alpha
      2 adrenergic receptors. The result suggested that a feed back circuit may exist
      between the hippocampus and the pineal, which balances the immunologic function
      in the body.

PMID- 12501663
TI  - [Research progresses on agmatine].

PMID- 12501664
TI  - [Progress in the research on CDK kinase inhibitor p21Cip1].

PMID- 12501665
TI  - [Effect of melatonin on sleep regulation].

PMID- 12501666
TI  - [The mechanisms of pathogenesis in Alzheimer's disease].

PMID- 12501667
TI  - [Glutamate receptors on retinal bipolar cells].

PMID- 12501668
TI  - [The progress on the modulation of hypoxia responsive gene (HRG)].

PMID- 12501669
TI  - [Gax gene and it's effects on the proliferation of vascular smooth muscle cells].

PMID- 12501670
TI  - [Progresses on selenophosphate synthetase].

PMID- 12501671
TI  - [Molecular basis of reverse cholesterol transport].

PMID- 12501672
TI  - [Molecular and cellular mechanism of fat-storing cell activation].

PMID- 12501673
TI  - [Neurologic science: comprehensive science of brain research].

PMID- 12501674
TI  - [Refolding of recombinant proteins in vitro].
AB  - Refolding of recombinant proteins is an important event in the downstream process
      of genetic engineering. On the basis of the mechanism of protein folding in
      vitro, general strategy of recombinant protein refolding is postulated, and major
      developments in recent years on this field are reviewed, including: molecular
      chaperone mediated refolding, detergent-assisted refolding, protein refolding in
      reverse micelle, addition of folding enhancer and methods for the formation of
      disulfide bond during protein refolding.

PMID- 12501675
TI  - [Ion channels of mammalian and human sperm membrane].
AB  - Ionic fluxes are thought to be important for sperm physiology. In recent years,
      using artificial membrane reconstitution and voltage clamp technique, different
      populations of ion channels, including K+, Na+, Ca2+ and Cl- channel, in
      mammalian and human sperm membrane were investigated. These studies shed lights
      to the understanding of some ionic basis underlying some mechanisms of sperm
      maturation, capacitation and gamete interaction. The results on human sperm ion
      channels also give us a chance to take it into clinic utility.

PMID- 12501676
TI  - [Extracellular ATP: effects, sources and fate].
AB  - The change of extracellular adenosine triphosphate (ATP) concentration affects
      many important physiological functions significantly. As a transmitter, ATP acts
      on neuro-effector junction directly and/or modulates the release of other
      neurotransmitters. By acting on the various P2-purinoceptors or ionic channels on
      the membrane, ATP also has some striking effects on cell activities. This review
      focused on the latest advances on the research of extracellular ATP in the
      respects of discovering and confirming ATP as a transmitter, the source, subtypes
      of P2-purinoceptors, the receptor-mediated reactions, and the degradation of
      extracellular ATP.

PMID- 12501677
TI  - [Morphological and physiological changes of the nervous system in chronic painful
      peripheral neuropathy].
AB  - Peripheral nerve injury may result in many kinds of sensory disorders such as
      hyperalgesia, dysesthesia, causalgia, etc. This paper mainly reviews the changes
      in morphology and physiological function occuring in the chronic painful
      peripheral neuropathy of two kinds of animal models which are now generally used
      to study the mechanisms of chronic neuropathic pain.

PMID- 12501678
TI  - [Immunomodulatory role of opioids in the central nervous system].
AB  - Endogenous and exogenous opioids can influence and modulate neuronal and glial
      cell function via an opioid receptor mediated mechanism, leading to either
      protection or damage of the brain. Opiates such as morphine have been postulated
      to promote the progression of HIV-1 and the development of secondary
      opportunistic infections. Kappa opioid receptor ligands, on the other hand, may
      play a neuroprotective role. More studies are needed to delineate how opioids
      exert their effects on glial cells as well as neurons with the goal of developing
      new therapeutic approaches for neurodegenerative disease.

PMID- 12501679
TI  - [Effects of glucocorticoids on cardiovascular response after microinjection of
      noradrenaline/neuropeptide Y into nucleus tractus solitarius and the underlying
      mechanism in rats].
AB  - The present study was designed to observe the effect of glucocorticoids in the
      NTS on cardiovascular regulation, and to explore the effect of glucocorticoids on
      cardiovascular responses to microinjection of NA/NPY into the NTS. A large dosage
      of Dex was found to evoke a decrease of blood pressure and heart rate, and an
      increase of serum NO concentration. A small dosage of Dex rapidly attenuated or
      even abolished the cardiovascular responses to NA/NPY microinjected into NTS, and
      this effect continued for a longer period. It indicates that the effect of Dex on
      cardiovascular responses to NA/NPY is mediated through both the genomic and non
      genomic pathways. As regards the non-genomic mechanism, it was found that the
      rapid inhibitory effect had nothing to do with the intracellular glucocorticoid
      receptors, but was mediated through the stimulation of GABAA receptor to decrease
      the depressor reflex, or decreasing the sensitivity of alpha 2-adrenergic
      receptor and inhibiting NO formation, or directly affecting the potassium and
      calcium channel in the membrane and altering the response of cardiovascular
      neurons in the NTS to NA/NPY.

PMID- 12501680
TI  - [The biological characteristics of endothelial cells of human umbilical vein and
      the mechanism of intracellular signal transduction].
AB  - We observed the synthesis and release of vasoactive polypeptides (VPs) in the
      endothelial cells of human umbilical blood vessels (HUVEC). The results showed:
      (1) The content of VPs in the endothelial cells of non-innervated human umbilical
      vessels is higher than that of mesenteric vessels. (2) These VPs are synthesized
      by endothelial cells and released into the outside of cell bodies. (3) VIP and SP
      can stimulate the proliferation of HUVEC, but somatostatin (SOM) inhibits it. (4)
      VIP and SP increase opening probability of the Ca2+ channel in the membrane of
      HUVEC, while SOM decrease it, but VIP, SP and SOM result in the increase of
      concentrations of intracytosolic free Ca2+ and cAMP, while decreasing that of
      cGMP in HUVEC. In conclusion, we proved that there are local regulatory
      mechanisms in non-innervated human umbilical blood vessels, and VPs within
      endothelial cells may play an important role.

PMID- 12501681
TI  - [Is LTP the neural basis of learning and memory?].

PMID- 12501682
TI  - [The mechanism of mitogen-activated protein kinase activation mediated by G
      protein-coupled receptor].

PMID- 12501683
TI  - [The cell messenger roles of the endogenous carbon monoxide in the cardiovascular
      system].

PMID- 12501684
TI  - [Cardiotrophin-1: a new cytokin that induces cardiac myocyte hypertrophy].

PMID- 12501685
TI  - [Neurturin: a relative of glial-cell-line-derived neurotrophic factor].

PMID- 12501686
TI  - [Properties and function of the calcium-activated potassium current of neurons].

PMID- 12501687
TI  - [Calreticulin, a calcium binding protein].

PMID- 12501688
TI  - [The endogenous circadian rhythm of suprachiasmatic nucleus and effects of light,
      glutamate and nitric oxide on its circadian rhythm].

PMID- 12501689
TI  - [Change and regulation of alpha-SM-actin in remodeling of vascular smooth muscle
      cells].

PMID- 12501690
TI  - [Adducin and hypertension].

PMID- 12501691
TI  - [Research progresses on guanylin].

PMID- 12501692
TI  - [Molecular mechanism of the expression and modulation of CYP3A gene].

PMID- 12501693
TI  - [Electrophysiological studies of two types of chloride channels in the membrane
      of parietal cells].

PMID- 12501694
TI  - [Melanocyte, melanogenesis and the adjustment of melanogenesis].

PMID- 12501695
TI  - [Advance in physiological study on taste].

PMID- 12501696
TI  - [Muller cells and retinal function].
AB  - Muller cells are the principal neuroglia cells in the retina. Recently, a lot of
      evidence indicate that there exist two-way communications between Muller cells
      and retinal neurons. Muller cells may modulate neuronal activity in the retina
      either indirectly through modifying neuronal microenvironment or directly by
      controlling the concentration of neuroactive substances in extracellular space,
      in addition to their general supporting and nourishing roles. Muller cells
      thereby play an important role in retinal function.

PMID- 12501697
TI  - [Effects of prion protein on central nervous system and the mechanisms of
      action].
AB  - The following questions are discussed in this paper: (1) Can the bovine prion
      protein PrpRES infect a man? (2) What is the route of PrPRES infection? (3) In
      what condition the PrPRES may infect animals, (4) What are the normal functions
      of PrPc at the surface of neurons and neuroglia cells, (5) What is the structure
      of the prion protein, (6) What is possible mechanism of the PrPRES destroying
      neurons. Finally, the two possible mechanisms of the PrPRES to affect central
      nervous system are analysed. One is to destroy the normal function of the PrPC,
      the other is to raise the sensibility of the neuron to the free radical and
      increase the content of the oxygen radical.

PMID- 12501698
TI  - [Signal transduction of alpha 1-adrenoceptors].
AB  - alpha 1-adrenoceptors activate multiple signal transduction pathways. In addition
      to the classic inositol phosphates-Ca2+ system and diacylglycerol-protein kinase
      C system, the phospholipase A2-arachidonic acid system, the tyrosine kinase
      phosphorylation system, the adenylate cyclase-cAMP system etc. were also
      involved. These signal transduction cascades interact complicatedly with each
      other as a network. The activation of one signal system can initiate, potentiate
      or inhibit other systems. They play pivotal role in diversified physiological and
      pathophysiological processes. Different alpha 1-adrenoceptor subtypes activate
      different signal transduction pathways. In some experiments, however, the
      differences are due to the different tissues or cells used.

PMID- 12501699
TI  - [Progress in the study of obesity gene].
AB  - The study of obesity is one of the most active and fast moving area in the basic
      biomedical research. In the past three years, scientists had cloned the obese
      gene, clarified the structure of leptin, nailed down and cloned the gene of
      leptin receptor, partly revealed the mechanisms of leptin's effects which make
      the study of obesity entering the molecular age. It shows an attractive
      perspective for human being to control the body weight and increase the health
      level. The recent progress of all these aspects is discussed in this review.

PMID- 12501700
TI  - [Progress in the study of mammalian selenoprotein].
AB  - Selenium is an essential trace element for animals and humans. Selenium exerts
      its biological function largely through selenoproteins. Up to now nine
      selenoproteins' cDNAs have been cloned and sequenced, which are cellular
      glutathione peroxidase (cGPX), extracellular glutathine peroxidase(eGPX),
      phospholipid hydroperoxidase glutathione peroxidase(PHGPX), gastrointestinal
      glutathione peroxidase (GPX-GI), type I iodothyronine 5'-deiodinase (ID I), type
      2 iodothyronine 5'-deiodinase(ID II), type III iodothyronine 5-deiodinase(ID
      III), selenoprotein P (Se-P) and selenoprotein W. In all these selenoproteins Se
      is incorporated into the protein molecule via the selenocysteinyl-tRNA which
      recognizes the specific UGA codons in mRNA to insert selenocysteine into the
      primary structure of selenoproteins.

PMID- 12501701
TI  - [Protective effects of schisanhenol, salvianolic acid A and SY-L on oxidative
      stress induced injuries of cerebral cells and their mechanisms].
AB  - Oxidative stress may play an important role in neuronal degenerative diseases
      such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral
      sclerosis. These disorders make the elderly not being able to live normally and
      move freely. So it is necessary to find effective antioxidants to prevent or cure
      the aged persons from diseases related to neuronal degeneration. Schisanhenol
      (Sal) and salvianolic acid A (Sal A) are known antioxidants which were isolated
      from Chinese herbs respectively. SY-L is a totally synthetic new compound. The
      results showed that Sal, Sal A and SY-L significantly protect cerebral cells from
      the injuries induced by oxidative stress.

PMID- 12501702
TI  - [Preconditioning: a general biological phenomenon and its mechanisms].
AB  - The present experiments observed the protective effects of ischemic
      preconditioning (PC) on different organs of rat. It was found that vascular
      protection of PC is one of the mechanisms of its organ protection. In the
      cultured neonatal rat (rabbit) cardiomyocytes and vascular smooth muscle cells
      (VSMC), it was observed that protein kinase C (PKC) activation and PKC-mediated
      protein phosphorylation were the common chains of PC cytoprotection. Basic
      fibroblast growth factor could mimic the cytoprotective effects of PC. It is
      indicated that pharmacological PC might have potential clinical application for
      ischemic diseases.

PMID- 12501703
TI  - [A review of some concepts of Parkinson's disease].

PMID- 12501704
TI  - [Cerebral ischemia injury and programmed cell death].

PMID- 12501705
TI  - [The advances in the study of the relation between angiotensionogen gene
      mutations and essential hypertension].

PMID- 12501706
TI  - [Recent advances in the studies of Midkine family].

PMID- 12501707
TI  - [Tumor necrosis factor and central nervous system].

PMID- 12501708
TI  - [Present understanding of intracellular signal transduction of interleukin-1].

PMID- 12501709
TI  - [The mechanisms of damage to biomolecules of hydroxyl radical mediated by iron].

PMID- 12501710
TI  - [Neurobiological properties of neurons in human neocortex in vitro].

PMID- 12501711
TI  - [New progress in the study of orientation sensitivity of visual cortical cells].

PMID- 12501712
TI  - [The role of epithelio-mesenchymal transformation in renal interstitial
      fibrosis].

PMID- 12501713
TI  - [Some advances on the study of glutamic acid decarboxylase].

PMID- 12501714
TI  - [The current status of mammalian ICE-like proteases].

PMID- 12501715
TI  - [Mechanism of bone mineral loss in microgravity].

PMID- 12501716
TI  - [The regulation of erythropoietin gene expression].

PMID- 12501717
TI  - On dealing with bias.

PMID- 12501718
TI  - Social genomics: genomic inventions in society. The nature of what's to come.
AB  - This paper identifies several kinds of intellectual mistakes that proponents of
      genetic engineering make, in defending their views and characterizing the views
      of their opponents. Results from research in the social sciences and humanities
      illuminate the nature of these mistakes. The mistakes themselves play a role in
      allowing proponents to gather support from other protagonists in the social
      controversies involving science and technology. Understanding the controversies
      requires understanding that innovations are components of complex and ill
      structured social problems; the "right answer" does not follow from scientific or
      technological breakthroughs. If the problems are identified correctly, issues of
      non-economic or non-market values and political and individual rights will need
      to be addressed.

PMID- 12501719
TI  - Assessing the value of transgenic crops.
AB  - In the current controversy about the value of transgenic crops, matters open to
      empirical inquiry are centrally at issue. One such matter is a key premise in a
      common argument (that I summarize) that transgenic crops should be considered to
      have universal value. The premise is that there are no alternative forms of
      agriculture available to enable the production of sufficient food to feed the
      world. The proponents of agroecology challenge it, claiming that agroecology
      provides an alternative, and they deny the claim that it is well founded on
      empirical evidence. It is, therefore, a matter of both social and scientific
      importance that this premise and the criticisms of it be investigated rigorously
      and empirically, so that the benefits and disadvantages of transgenic-intensive
      agriculture and agroecology can be compared in a reliable way. Conducting
      adequate investigation about the potential contribution of agroecology requires
      that the cultural conditions of its practice (and, thus, of the practices and
      movements of small-scale farmers in the "third world") be strengthened--and this
      puts the interests of investigation into tension with the socio-economic
      interests driving the development of transgenics. General issues about
      relationship between ethical argument and empirical (scientific) investigation
      are raised throughout the article.

PMID- 12501720
TI  - Editorial independence at medical journals owned by professional associations: a
      survey of editors.
AB  - The purpose of this study was to assess the degree of editorial independence at a
      sample of medical journals and the relationship between the journals and their
      owners. We surveyed the editors of 33 medical journals owned by not-for-profit
      organizations ("associations"), including 10 journals represented on the
      International Committee of Medical Journal Editors (nine of which are general
      medical journals) and a random sample of 23 specialist journals with high impact
      factors that are indexed by the Institute for Scientific Information. The main
      outcome measures were the authority to hire, fire, and oversee the work of the
      editor; the editor's tenure and financial compensation; control of the journal's
      budget; publication of material about the association; and the editor's
      perceptions about editorial independence and pressure over editorial content. Of
      the 33 editors, 23 (70%) reported having complete editorial freedom, and the
      remainder reported a high level of freedom (a score of > or = 8, where 10 equals
      complete editorial freedom and 1 equals no editorial freedom). Nevertheless, a
      substantial minority of editors reported having received at least some pressure
      in recent years over editorial content from the association's leadership (42%),
      senior staff (30%), or rank-and-file members (39%). The association's board of
      directors has the authority to hire (48%) or fire (55%) the editor for about half
      of the journals, and the editor reports to the board for 10 journals (30%).
      Twenty-three editors (70%) are appointed for a specific term (median term = 5
      years). Three-fifths of the journals have no control over their profit, and the
      majority of journals use the association's legal counsel and/or media relations
      staff. Stronger safeguards are needed to give editors protection against pressure
      over editorial content, including written guarantees of editorial freedom and
      governance structures that support those guarantees. Strong safeguards are also
      needed because editors may have less freedom than they believe (especially if
      they have not yet tested their freedom in an area of controversy).

PMID- 12501721
TI  - Seven ways to plagiarize: handling real allegations of research misconduct.
AB  - As the research integrity officer at my university for two years, I handled eight
      allegations of plagiarism. These eight cases show that initial appearances can be
      mistaken, that policies for handling allegations of research misconduct cannot
      cover every contingency, and that many cases can be resolved collegially without
      resort to formal procedures.

PMID- 12501722
TI  - Exploring the role of the research integrity officer. Commentary on 'Seven ways
      to plagiarize: handling real allegations of research misconduct'.

PMID- 12501723
TI  - Self-plagiarism and dual and redundant publications: what is the problem?
      Commentary on 'Seven ways to plagiarize: handling real allegations of research
      misconduct'.

PMID- 12501724
TI  - Personal meaning and ethics in engineering.
AB  - The study of engineering ethics tends to emphasize professional codes of ethics
      and, to lesser degrees, business ethics and technology studies. These are all
      important vantage points, but they neglect personal moral commitments, as well as
      personal aesthetic, religious, and other values that are not mandatory for all
      members of engineering. This paper illustrates how personal moral commitments
      motivate, guide, and give meaning to the work of engineers, contributing to both
      self-fulfillment and public goods. It also explores some general frameworks for
      thinking about these commitments and calls for further exploration of them.

PMID- 12501725
TI  - Ethical and economic issues in the use of zero-emission vehicles as a component
      of an air-pollution mitigation strategy.
AB  - The air pollution generated by motor vehicles and by static sources is, in
      certain geographic areas, a very serious problem, a problem that exists because
      of a failure of the marketplace. To address this marketplace failure, the State
      of California has mandated that by 2003, 10% of the Light-Duty Vehicle Fleet
      (LDV) be composed of Zero-Emission Vehicles (ZEVs). However, the policy-making
      process that was utilized to generate the ZEV mandate was problematic and the
      resulting ZEV mandate is economically unsound. Moreover, an ethical analysis,
      based primarily upon the work of John Rawls, suggests that implementation of the
      California ZEV mandate is--in spite of the wide latitude that ought to be given
      to policy decision makers--unethical. A more ethical and economically efficient
      approach to the pollution caused by marketplace failure is one that relies on
      market incentives and thereby achieves the desired improvement in air quality by
      appealing both to the self-interest of motorists and to those businesses that are
      directly or indirectly involved with the automobile industry. Such an approach
      would take better advantage of the creative forces of the market and improvements
      in technology over time and avoid the infringements on individual liberty and
      fairness embodied in the ZEV mandate.

PMID- 12501726
TI  - Animal spare parts? A Canadian public consultation on xenotransplantation.
AB  - Xenotransplantation, or the use of animal cells, tissues and organs for humans,
      has been promoted as an important solution to the worldwide shortage of organs.
      While scientific studies continue to be done to address problems of rejection and
      the possibility of animal-to-human virus transfer, socio-ethical and legal
      questions have also been raised around informed consent, life-long monitoring,
      animal welfare and animal rights, and appropriate regulatory practices. Many
      calls have also been made to consult publics before policy decisions are made.
      This paper describes the Canadian public consultation process on
      xenotransplantation carried out by the Canadian Public Health Association in an
      arm's length process from Health Canada, the ministry overseeing government
      health policy and regulation. Focusing on six citizen for a conducted around the
      country patterned after the citizen jury deliberative approach, the paper
      describes the citizen panelists' recommendations to hold off on proceeding with
      clinical trials and the rationales behind this recommendation. The consultation
      process is discussed in the context of constructive technology assessment, a
      framework which argues for broader input into earlier stages of technology
      innovation, particularly at the technology design stage.

PMID- 12501727
TI  - Consensus conference on environmental values in radiation protection: a report on
      building consensus among experts.
AB  - During the fall of 2001 (October 22-25), The Norwegian Radiation Protection
      Authority (NRPA) and the Agricultural University of Norway arranged a consensus
      conference on the protection of the environment against ionising radiation. The
      motive for the conference was the need to study the ethical and philosophical
      basis for protection of nature in its own right. The conference was funded by
      Nordic Nuclear Safety Research (NKS), in cooperation with the International Union
      of Radioecology (IUR). The National Committee for Research Ethics in Science and
      Technology (NENT) was hired as facilitators for the consensus process. This paper
      will give a brief outline of the aims and method of the conference,
      distinguishing these from other kinds of consensus conferences. The paper ends
      with some general reflections on the appropriateness of seeking consensus on
      ethics-related issues among experts.

PMID- 12501728
TI  - After the genie is out of the bottle, what then?

PMID- 12501729
TI  - How nursing matters.

PMID- 12501730
TI  - Responses to "Rational suicide".

PMID- 12501731
TI  - Responses to "Rational suicide".

PMID- 12501732
TI  - Responses to "Rational suicide".

PMID- 12501733
TI  - Priorities for nursing research in Korea.
AB  - PURPOSE: To identify priorities for nursing research in Korea. METHODS: A
      national sample of nurses in academic and clinical settings, representing varied
      clinical specialties, participated in two rounds of a Delphi survey. Participants
      listed five most important nursing research problems rated on three dimensions:
      the degree of nurses' lead role, contribution to nursing profession, and nurses'
      contribution to health and welfare of patients and clients. A total of 29
      research areas were derived from 1,013 research problems identified from the
      Delphi surveys, and 26 expert panel members who participated in a 1-day workshop
      to determine the priority of these areas. Key words of 706 research articles
      published in the major nursing research journals in Korea were analyzed to
      identify priorities. RESULTS: In the two rounds of Delphi surveys 347 of 1,047
      nurses participated (31%-33% response rates respectively). To three research
      areas common to both Delphi survey and literature analysis were: clinical nursing
      practice, nursing education, and nursing research. Cultural nursing was rated the
      lowest in the Delphi survey but was rated third by the expert panel members.
      CONCLUSIONS: In the clinical practice area, research on the advanced practice
      nursing system was the first priority research problem followed by development of
      nursing interventions, clinical competency, quality and effectiveness of nursing
      care, and standardized nursing tasks. Research on home health care, nursing
      education, utilization of nursing research, and geriatric nursing were other
      areas of priority. Nurses around the world are encouraged to develop
      collaborative research projects based on common priority areas.

PMID- 12501734
TI  - A review of nursing research on blood pressure.
AB  - PURPOSE: To provide this second 10-year review of nursing research on blood
      pressure (BP) and to focus attention on incorporating biopsychosocial factors
      affecting BP in nursing research. ORGANIZING CONSTRUCT: Blood pressure is a
      dynamic, multidimensional, cardiovascular indicator of a person's state rather
      than a one-dimensional static measurement. METHODS: This 10-year literature
      review 1990-1999 included 54 nursing research articles with BP as an outcome
      measure. Four nursing research journals were reviewed to identify all nurse
      authored articles investigating BP as an outcome variable in adult populations.
      Inclusion of individual characteristics, environmental factors, dynamic nature of
      blood pressure, and interpersonal aspects of blood pressure were assessed for
      each article. FINDINGS: Age, gender, and health status were mentioned
      consistently in both decades. Reporting of socioeconomic, occupational,
      educational, activity, and martial status remained low. Descriptions of
      environments increased, and automated devices were the most common method for BP
      assessment. Less than half of the articles included a description of the person
      measuring the BP. Measurements of BP under multiple conditions increased, but
      measurement within conditions did not. CONCLUSIONS: Advances in technology and
      data analysis have increased knowledge of the dynamic nature of BP, but
      recognition of the complex nature of BP has not progressed rapidly over the last
      2 decades.

PMID- 12501735
TI  - The experience of Italians caring for family members with Alzheimer's disease.
AB  - PURPOSE: To obtain a more complete understanding of the experience of Italian
      caregivers of people with Alzheimer's Disease (AD). DESIGN AND METHODS: In this
      phenomenological study of AD Italian caregivers, the participants were 26 family
      caregivers (6 men and 20 women, of whom 19 were spouses and 7 were children).
      FINDINGS: Six themes were identified in this analysis: changes in relationships,
      changes in lifestyle, difficulties in caring, hopes and fears for the future,
      family duty, and respectful treatment. Caregivers experienced profound changes in
      their lives, including changes in their relationships with patients, in their
      lifestyles, and in their relationships with other family members. Caregivers
      experienced difficulties in caring because of their lack of knowledge about the
      illness and the lack of support from the National Health System. Participants
      hoped to not see their loved ones' conditions worsen and hoped to see positive
      results from prescription medications. Moreover, they hoped that God would help
      them go on. Some caregivers feared that the illness was hereditary and that they
      would not be able to cope with it. The Italian caregivers' respectful treatment
      of the patients demonstrated their profound sense of family duty, which included
      encouraging the patients to do self-care and occupational activities.
      CONCLUSIONS: Similarities and differences among Italian caregivers and those in
      other countries are discussed, and implications for Italian health professionals
      and directions for future research are addressed.

PMID- 12501736
TI  - The efficacy of tailored interventions.
AB  - PURPOSE: To evaluate the efficacy of Tailored Informational Interventions (TIs)
      compared to Standard Informational Interventions (SIs) and to determine whether
      efficacy varies by type of behavior, use of feedback, type of delivery channel,
      dose of the intervention, or time. METHODS: Cooper's method of literature
      integration (Cooper, 1989; Cooper & Hedges, 1994) was used. Eighty-five articles
      were located that contained the word tailoring in the title or abstract; 20 met
      criteria for inclusion. FINDINGS: Participants preferred TIs to SIs, perceived
      that the TIs were personal, and read and remembered more of the TI information.
      TIs were more effective than were SIs in 50% of studies. The effects of tailored
      and standard interventions were equivocal in the remaining 50% of studies. TIs
      had small increases in effect sizes compared to SIs. The efficacy of TIs differed
      by type of behavior. TIs had greater efficacy when ipsative feedback (comparing
      current to past behavior) was included as part of the intervention than when the
      intervention did not include such feedback. Repeated versus single administration
      of TIs did not affect health behaviors. The efficacy of TIs changed over time in
      some studies, but the pattern of change was not consistent. CONCLUSIONS: Tailored
      interventions could be improved by (a) identifying the most salient
      characteristics to be tailored, (b) further delineating essential components of
      TIs, (c) determining the efficacy of different delivery channels, (d) determining
      factors that moderate effects of TIs, and (e) clarifying whether the efficacy of
      TIs changes over time.

PMID- 12501737
TI  - Emotional distress and prenatal attachment in pregnancy after perinatal loss.
AB  - PURPOSE: To evaluate the association of previous perinatal loss with parents'
      levels of depressive symptoms, pregnancy-specific anxiety, and prenatal
      attachment in a subsequent pregnancy, and to determine whether higher levels of
      depressive symptoms and pregnancy-specific anxiety were associated with prenatal
      attachment. DESIGN: A three-group comparative design was used to collect cross
      sectional survey data. The sample consisted of 103 couples who were in the second
      trimester of pregnancy: 40 couples who had a perinatal loss in a previous
      pregnancy, 33 couples were pregnant for the first time, and 30 couples had a
      history of prior successful pregnancies. METHODS: Structured questionnaires via
      in-person or telephone interviews were used to measure depressive symptoms,
      pregnancy-specific anxiety, and prenatal attachment. FINDINGS: Couples with a
      history of perinatal loss had higher levels of depressive symptoms and pregnancy
      specific anxiety than did couples with past successful pregnancies and no losses;
      mothers had higher levels of symptoms than did fathers in all groups, Couples
      with and without a history of perinatal loss did not differ in their level of
      prenatal attachment in the current pregnancy. CONCLUSIONS: These findings do not
      support the theory that depressive symptoms and pregnancy-specific anxiety affect
      subsequent parent-infant attachment in a pregnancy after perinatal loss. However,
      they do provide insight into the continuing influence of parents' previous loss
      experience on their depressive symptoms and pregnancy-specific anxiety in
      subsequent pregnancies. Families should be assessed to examine the potential long
      term influence of emotional distress as a result of prior perinatal loss.

PMID- 12501738
TI  - Hydrotherapy in labor.
AB  - PURPOSE: To review the literature on hydrotherapy in labor to direct prescription
      of the intervention and design studies to test its effectiveness. METHODS:
      Studies of hydrotherapy were identified via searching literature and electronic
      databases. FINDINGS: A primary effect of immersion is a central blood volume
      bolus, which occurs almost immediately after bathing begins. Subjective maternal
      responses to bathing in labor have been favorable. No maternal or infant
      infections have been attributed to bathing by parturients with either intact or
      ruptured membranes. Maternal bathing in labor does not appear to affect infant
      Apgar scores or stress hormones at birth. No clear evidence exists to indicate
      that hydrotherapy increases cervical dilation, increases fetal descent, reduces
      uterine dyskinesia, shortens labor, decreases use of epidurals or analgesia, or
      decreases rates of operative delivery or hemorrhage. CONCLUSIONS: Study findings
      indicate support for using hydrotherapy for relief of rapid pain and anxiety in
      labor. A methodical approach must be taken to determine for whom and under what
      circumstances intervention with hydrotherapy in labor is efficacious. Studies of
      the maternal and fetal effects of hydrotherapy in labor, including mechanisms of
      action, as well as large, prospective, randomized clinical outcome trials with
      control for intervening variables, are needed to help practitioners decide
      whether to prescribe hydrotherapy.

PMID- 12501739
TI  - Building a model of self-care for health promotion in aging.
AB  - PURPOSE: To synthesize knowledge about self-care in older community-dwelling
      people, identify essential dimensions of self-care related to health promotion
      and well-being in aging, and organize the findings into a literature-based,
      integrated model with applicability in practice, research, and education.
      ORGANIZING CONSTRUCT: Self-care and health promotion. Related concepts included
      self-concept, self-care ability, and self-care activity. METHODS: These terms
      were used to search Medline, CINAHL, and PsycINFO data bases. Theoretical and
      research articles from the last decade that related to self-care and health
      promotion in community-dwelling elders and that provided recommendations for
      education and practice were selected for inclusion in the analysis. FINDINGS:
      Self-care for health promotion in independent elders is multidimensional.
      Synthesis of literature findings resulted in development of the model of Self
      care for Health Promotion in Aging, with five dimensions: internal and external
      environment, self-care ability, education, self-care activity, and outcomes.
      Examples of education plans that are developed in partnership with clients to
      promote better health and maximize quality of life are presented. CONCLUSIONS:
      Findings from current theoretical and empirical literature were synthesized to
      develop a model of self-care for health promotion in aging. Suggestions are made
      regarding application of the model in clinical practice and further theory
      building and hypothesis testing.

PMID- 12501740
TI  - The health effects of work-based welfare.
AB  - PURPOSE: To identify effects of work-based welfare on the health and well-being
      of participants. Data included the needs and experiences of people in the work
      based welfare program. DESIGN: The population for this qualitative study was
      adults enrolled in the work-based welfare program in a large urban community in
      the U.S. Midwest. The sample was 34 women who were enrolled in this program. The
      interview settings were an inner-city adult education center, an inner-city
      church, a subsidized housing development, or homes of participants. Data were
      collected between July 1999 and June 2000. METHODS: Snowball sampling was used to
      identify participants. Instruments used for this report were a semi-structured
      interview guide, a demographic data sheet, and the General Well-being Schedule.
      FINDINGS: The human costs to people enrolled in work-based welfare included
      anxiety and depression as well as negative effects on health and well-being.
      Participants also reported positive effects on well-being and empowerment.
      CONCLUSIONS: The findings indicate the complex interplay of the socioeconomic
      environment, mental and physical health, and the well-being of families. The
      women's perceptions of the effects that welfare policy has had on them and their
      families indicate the need for a broader response to poverty than the largely
      economic response of work-based welfare.

PMID- 12501741
TI  - Lessons learned from testing the quality cost model of Advanced Practice Nursing
      (APN) transitional care.
AB  - PURPOSE: To describe the development, testing, modification, and results of the
      Quality Cost Model of Advanced Practice Nurses (APNs) Transitional Care on
      patient outcomes and health care costs in the United States over 22 years, and to
      delineate what has been learned for nursing education, practice, and further
      research. ORGANIZING CONSTRUCT: The Quality Cost Model of APN Transitional Care.
      METHODS: Review of published results of seven randomized clinical trials with
      very low birth-weight (VLBW) infants; women with unplanned cesarean births, high
      risk pregnancies, and hysterectomy surgery; elders with cardiac medical and
      surgical diagnoses and common diagnostic related groups (DRGs); and women with
      high risk pregnancies in which half of physician prenatal care was substituted
      with APN care. Ongoing work with the model is linking the process of APN care
      with the outcomes and costs of care. FINDINGS: APN intervention has consistently
      resulted in improved patient outcomes and reduced health care costs across
      groups. Groups with APN providers were rehospitalized for less time at less cost,
      reflecting early detection and intervention. Optimal number and timing of
      postdischarge home visits and telephone contacts by the APNs and patterns of
      rehospitalizations and acute care visits varied by group. CONCLUSIONS: To keep
      people well over time, APNs must have depth of knowledge and excellent clinical
      and interpersonal skills that are the hallmark of specialist practice, an in
      depth understanding of systems and how to work within them, and sufficient
      patient contact to effect positive outcomes at low cost.

PMID- 12501742
TI  - Examination of primary care characteristics in a community-based clinic.
AB  - PURPOSE: To (a) examine the reliability and validity of the Primary Care
      Assessment Survey (PCAS), (b) describe the primary care characteristics of a
      community-based clinic in an underserved area in Appalachia, (c) examine the
      relationships between primary care characteristics and socioeconomic factors, (d)
      compare and contrast patients who have regular providers of care with those who
      did not have regular providers of care; and (e) examine provider primary care
      characteristics that predict comprehensive knowledge of patients. DESIGN: Data
      for this cross-sectional survey (N = 227) were collected over a 4-month period
      using face-to-face interviews at a not-for-profit, community-based clinic serving
      patients in three Appalachian states in the southeastern United States. METHODS:
      The PCAS was used to measure 11 domains of primary care provider performance and
      to identify and group patients who had regular providers of care (n = 126) and
      patients who did not have regular providers of care (n = 98) at the clinic.
      FINDINGS: Cronbach's coefficient alpha for the total scale was .74 after deleting
      one subscale. Factor analysis revealed one PCAS dimension, Communication,
      accounting for 44% of the total variance. Primary care providers' Interpersonal
      Treatment and Longitudinal Continuity were predictors of Comprehensive Knowledge
      of the patient and accounted for 26% and 6% of the variance, respectively.
      CONCLUSIONS: The PCAS showed evidence of reliability and validity with
      underserved Appalachian patients receiving care in a community-based clinic. The
      findings showed that patients receiving care from primary care providers had
      sustained relationship that affected communication aimed at improving primary
      care outcomes.

PMID- 12501743
TI  - Revisioning nursing scholarship.
AB  - PURPOSE: To propose a universal model of nursing scholarship that (a) indicates
      the importance of professional practice disciplines, (b) incorporates the
      synthesis of intellectual pursuit with social change, and (c) is holistic in its
      design. ORGANIZING CONSTRUCT: Scholarship, traditionally viewed as part of or
      generated in the university enterprise, must be an expectation in all settings in
      which a community of scholars from both discipline and practice can and do
      coexist. METHODS: Review and synthesis of the literature on scholarship, nursing
      scholarship, nursing as a practice discipline. FINDINGS: The history, culture,
      and intellectual property of nursing comprise an appropriate basis for adopting a
      universal holistic model of scholarship built upon a set of universal assumptions
      about nursing scholarship. As a discipline and a profession, nursing should
      include four connected domains in a universal holistic model of scholarship:
      knowing, teaching, practice, and service. CONCLUSIONS: Confirmation of this
      universal holistic model of scholarship can contribute significantly to a larger
      nursing identity. Use of universal holistic model of nursing scholarship
      indicates responsibility of the nursing profession collectively and all nurses
      individually. Additional work is needed to understand how a universal holistic
      model of nursing scholarship evolves across cultures, domains, and work settings.

PMID- 12501744
TI  - Building research competence in nursing through mentoring.
AB  - PURPOSE: To explore how mentoring can be used to build research competence in
      nursing in various professional and geographic settings. ORGANIZING CONSTRUCT:
      The traditional concept of mentoring in interdisciplinary health professions and
      its application to nursing research. METHODS: Literature review of MEDLINE and
      CINAHL databases 1990-2001 and personal reflections on mentoring and mentored
      experiences. FINDINGS: Mentoring relationship models identified include:
      traditional mentor and protege, team, peer, inclusive, and mentoring forward. E
      mentoring strategies facilitate interactions for long-distance relationships.
      Discrete projects, multiple mentor sources, and mutually beneficial peer
      relationships can enable mentoring across one's career. Psychosocial dimensions
      of mentoring support creative work. When scholarly productivity with funded
      research is the desired outcome, intense involvement of a protege with an expert
      researcher is essential. CONCLUSION: Choices among mentoring models can be made
      in accordance with resources, priorities, and objectives congruent with a given
      nursing setting and time, but optimum scholarly productivity requires experts and
      sustained support.

PMID- 12501745
TI  - Influenza vaccine-associated adverse events: results of passive surveillance,
      Canada 2001-2002.

PMID- 12501746
TI  - Recommendations for the screening and prevention of tuberculosis in patients with
      HIV and the screening for HIV in tuberculosis patients and their contacts.

PMID- 12501747
TI  - A deadly passage to India.

PMID- 12501748
TI  - 'Electronic morphine'.

PMID- 12501749
TI  - When doctors put patients at risk.

PMID- 12501750
TI  - Better outcomes for less than $15.

PMID- 12501751
TI  - You just received a subpoena. Now what?

PMID- 12501752
TI  - Helping kids breathe easier.

PMID- 12501753
TI  - Tame the accounts receivable beast.

PMID- 12501754
TI  - The night I totally lost it.

PMID- 12501755
TI  - More hours, more patients, no raise?

PMID- 12501756
TI  - When a lawyer wants a patient's records.

PMID- 12501757
TI  - [Preparation of manuscripts for medical journals].

PMID- 12501758
TI  - [Th1 lymphocytes in patients with extrinsic asthma].
AB  - BACKGROUND: Bronchial asthma is a multifactorial disease affecting the
      functionality of the bronchial tree and immunological changes. OBJECTIVE: To
      determine if lymphocytes Th-1 have a role in extrinsic asthma of Mexican
      patients. MATERIAL AND METHODS: We included in the study 39 patients with
      extrinsic asthma, living in Mexico City, and 27 healthy subjects, without allergy
      antecedents, with nutritional and immunological characteristics similar. It was
      determined the following data: production of IL-2 (in 5 patients and 5 controls),
      its receptor (in all participants), IFN-g (in 8 patients and 5 controls), and TNF
      a (in 8 patients and 5 controls). RESULTS: Values of IL-2, its receptor and IFN
      gamma were higher in patients than in controls, with significant differences.
      There were not important differences about TNF-alpha. CONCLUSIONS: Even causes of
      action change between lymphocytes Th-1 and Th-2 are not known, it is confirmed
      the moving from Th-2 to Th-1 as an active phenomenon in asthma.

PMID- 12501759
TI  - [Measurement of cytokines in patients with exercise-induced asthma treated with
      anti-leukotrienes].
AB  - BACKGROUND: Exercise-induced asthma is defined as the transient broncho-spasm,
      that occurs after 3 to 8 minutes of continuous exercise; one of two mechanisms
      are implicated: the first is given by a hyper-osmolar environment interchange
      with the warm respiratory air and the water loss, the second due to reactive
      hyperemia or bronchial blood vessels edema. OBJECTIVES: To determine the
      effectiveness and safety of Zafirlukast treatment in exercise induce asthma, and
      in mild and moderated persistent bronchial asthma. Evaluate the security with
      laboratory test IL-2, IL-4, INFg, and CD69, to determinate TH1 and Th2 cells,
      laboratory and thorax x-ray determinations before and after zafirlukast treatment
      in exercise induce asthma, plus the functional respiratory test, and assert the
      clinical and adverse reaction with Zafirlukast. MATERIAL AND METHODS: A open,
      prospective, longitudinal study. Challenge test on a treadmill for 8 minutes.
      Twenty patients from the Allergy Service at Lic. Adolfo Lopez Mateos Hospital,
      ISSSTE, in Mexico City, fifteen female and five males. Aged 15 to 35 years. There
      was a control group of ten healthy subjects with similar age and sex. The drug
      Zafirlukast was administered 20 mg twice a day for eight weeks, with patient's
      informed and signed consent. Laboratory test: Blood Cell count, transaminases,
      bilirubins A, G, M and E immunoglobulins thorax X-ray, electrocardiogram,
      functional respiratory test before and after treatment. RESULTS: Zafirlukast
      blocked exercise induced asthma in the early and late phases. There was a
      statistically significant improvement of a VEF-1 after exercise with a p > 0.001;
      furthermore, there was significant improvement in the mid-spiratory speed before
      the exercise with a p > 0.05. The mid-spiratory speed after the exercise,
      improved (p > 0.01). There were no collateral reactions, such as Churg-Strauss,
      only transitory headache in six and nauseas in two. There were no statistically
      significant changes in the cytokines assessment. CONCLUSIONS: There were no
      statistically significant changes in the cytokines assessments, in four cases the
      IL-4 decreased after the treatment. The anti-leukotriene improved the
      bronchospastic answer during the early and late phases, reducing the FEV-1,
      decreasing the recovering phase.

PMID- 12501760
TI  - [Limitation of the development of physical activity in asthmatic children and
      adolescents].
AB  - BACKGROUND: Asthma can, direct or indirect cause physical limitations in
      asthmatic patients affecting their quality of life. OBJECTIVE: To identify
      factors that influence and limit the physical activities in asthmatic children
      and teenagers. MATERIAL AND METHODS: This was a descriptive and observational
      study in 83 asthmatic children and teenagers, between 6 to 18 years old, who
      attended a summer camp for asthmatic patients. They answered a questionnaire
      about the kind of physical activities that they regularly, in order to identify
      factors that limit their physical activities. In the camp, some of them had to
      stop exercising because of an asthma crisis. For the statistical analysis, we
      used central and percentage tendency. RESULTS: Sixty patients (72.3%) regularly
      practiced some kind of sport being the most frequent soccer (36.7%), swimming
      (20.1%), athletics (8.4%) and basketball (8.4%). Of the 23 children and teenagers
      that did not regularly practice any sport, 19 of them were between 5 to 10 years
      old. In the first group, 28 (46.7%) said that they had to stop exercising when
      suffered an asthma crisis. In the camp, eight children (9.7%) had to stop their
      physical activities because an asthma crisis. Only 47 children (56.6%) knew the
      kind of physical activity in which they could participate and the correct way to
      perform it; as a result of an educational process. CONCLUSION: In our community,
      the development of asthma crisis and the lack of adequate physical education are
      facts that limit exercise practicing in asthmatic children and teenagers.

PMID- 12501761
TI  - [Gastroesophageal reflux disease in pediatric patients with asthma].
AB  - BACKGROUND: Nowadays, the gastroesophageal reflux is a predisposing factor for
      the development of asthmatic attacks. OBJECTIVE: To determine the prevalence of
      gastroesophageal reflux in pediatric patients with asthma of the Service of
      Allergy and Immunology at the Hospital Regional Lic. Adolfo Lopez Mateos.
      MATERIAL AND METHODS: It was made an observational study from July 2000 to July
      2001. Gastroesophageal gammagraphic and endoscopy (with taking of esophageal
      biopsy) were carried out to each of the patients in order to find out if there
      was gastroesophageal reflux. RESULTS: 112 patients with moderate persistent
      asthma (54 women and 58 men) were included and divided in three different age
      groups (group I, from 1 to 5 years old; group II, from 6 to 10 and III, from 11
      to 16 years old). The prevalence of gastroesophageal reflux was 138, 100 and 93,
      respectively, being specially high in males. Differences in the prevalence among
      different groups were statistically significant between group I and II (p <
      0.001) and between I and III (p < 0.001). Significant changes were not observed
      between group II and III (p = NS). CONCLUSIONS: The prevalence of
      gastroesophageal reflux the structured was high, situation directly related with
      the diagnostic suspicion in our asthmatic population.

PMID- 12501762
TI  - [Relation between Helicobacter pylori and atopic diseases].
AB  - The rise in the incidence of atopic diseases in the last years is associated to a
      greater prevalence of viral and bacterial infections. The infections facilitate a
      chronic inflammatory process that is directly related to the sensibilization of
      mast cells which favors manifestations of allergic diseases. Within the proposed
      bacteriological agents as causes of is Helicobacter pylori. This work is a
      bibliographical revision and concludes that there is not evidence of the direct
      causal relation between infection by Helicobacter and allergic diseases; however,
      it can play an indirect role. Controlled and randomized studies are necessary to
      know accurately this relation because the eradication treatment could be a real
      alternative in these patients handling.

PMID- 12501763
TI  - [Common variable immunodeficiency. Report of 2 cases].
AB  - We report two cases with common variable immunodeficiency. Both of them had
      gammaglobulin concentration lower than 300 mg/dL and evolved differently. The
      first one had three pneumonic episodes that responded satisfactorily to
      antibiotics. Today, this patient presents only two or three sinusitis clinical
      schemes per year, and has a good response to treatment. The second one has a bad
      evolution and presents hematological problems like thrombocytopenia and
      neutropenia. She also suffers lymphoid nodular hyperplasia in the intestinal
      tract and atrophy in the intestinal. These cases illustrate the wide clinical,
      immunological and genetic variety of the syndrome.

PMID- 12501764
TI  - [Results of an endoscopic study in patients with long-term tubal dysfunction].
AB  - Basing on the findings of a comprehensive endoscopic examination of 121 patients
      with tubal dysfunction, a clinicoanatomic systematization was made of pathologic
      changes in the area of the pharyngeal opening of the auditory tube. A correlation
      was found between long-lasting tubal dysfunction and diseases of the nose,
      paranasal sinuses, nasopharynx and pharynx.

PMID- 12501765
TI  - [Audiometry in critical frequency bands of hearing].
AB  - The analysis of the choice and distribution of the fixed frequencies in the
      course of audiometry and mechanisms of automatic regulation in the hearing system
      (HS) gave grounds to suppose that: 1) HS is rather a multichannel system than a
      single channel, the number of channels being equal to the number of frequency
      critical acoustic bands (that is 24); 2) not one but 24 mechanisms of threshold
      hearing adaptation operate in HS, one for each critical hearing band; 3) the
      number of fixed frequencies at which audiometry is made (125 Hz-8 kHz) should be
      21 while now it is 9 and these frequencies should not change by ostave, but must
      correspond to central frequencies of critical hearing bands this number of
      frequencies being optimal.

PMID- 12501766
TI  - [DNA diagnosis in congenital and early childhood hypoacusis and deafness].
AB  - Congenital deafness affects 0.05-0.1% children. 90% of them were born from
      parents with normal hearing. There were no hearing defects in their families. In
      70% of deafness cases deafness is the only symptom of the disease and is thought
      to be non-syndromal. Hypoacusis of unclear etiology may be congenital in 50%
      cases. Half of cases of severe autosomic-recessive non-syndromal hypoacusis
      (deafness) appear because of changes in only one gene--gene of connexine-26. Two
      thirds of the defects in this gene arise because of one mutation--35delG. Mean
      rate of this mutation carriage in Russia is over 2%. Identification of mutation
      35delG in gene Cx26 is performed with the use of polymerase chain reaction.
      Genetic examination of 75 children with isolated hypoacusis (deafness) has
      detected deletion 35delG in both gene copies in 23 children (30%). 10 patients
      (13.4%) had mutation 35delG only in one copy of gene Cx26. Hearing defects in the
      latter may be related with the presence of another mutation in the same gene. A
      total of 33 patients (42%) carried deletion 35delG. According to our findings,
      the changed genotype is characterized primarily by bilateral neurosensory
      hypoacusis of the third-fourth degree. Weaker loss of hearing is rare. Thus,
      mutations in connexine gene26 present a problem for parents with normal hearing.
      Therefore, families with a deaf child should be referred for medicogenetic
      consultations.

PMID- 12501767
TI  - [Some aspects of adjustment of a speech processor of the cochlear implants Combi
      40/40+ and Tempo+].
AB  - The author describes how to perform the first switching on the speech processors
      (SP) and subsequent adjustment of cochlear implant SP. These SP Combi-40/40+ and
      Tempo+ were adjusted in 25 patients aged 2 to 27 years who lost hearing at the
      age 0-26 years. By problems arising at the first switching on and adjustment, all
      the implanted patients can be divided into three groups: postlingual--those who
      lost hearing after speech establishment; perilingual--those who lost hearing step
      by step starting from hypoacusis; prelingual--those who had lost hearing before
      they could speak. How to adjust SP in each group of the above patients is
      described.

PMID- 12501768
TI  - [Condition of the larynx affected by the laryngeal mask during general
      anesthesia].
AB  - A new generation artificial airway--a laryngeal mask (LM)--was examined for
      effects on a laryngeal function in general anesthesia. Topographic-anatomic
      characteristics of the upper respiratory tracts which make impossible an adequate
      wearing of LM as well as frequency and severity of laryngeal LM-induced
      complications were specified. The comparison of the changes in the laryngopharynx
      and larynx due to LM and endotracheal tube has demonstrated that LM is more safe
      for anatomic and functional state of the larynx and for mucosa of the upper
      respiratory tracts than the tube. LM provides general anesthesia in problematic
      intubation. Employment of LM raises quality of anesthesia, reduces the number of
      intra- and postoperative laryngeal complications in conduction of general
      anesthesia.

PMID- 12501769
TI  - [Morphological changes in airway tissues in patients with laryngeal and tracheal
      deformations].
AB  - A histomorphological picture of surgically removed cicatricial tissue was
      compared in two groups of patients with deformations of the larynx and trachea:
      operated within 1-2 months after trauma and 6-12 months after it. Chronic
      productive inflammation was found in the tissue early after trauma, while later,
      mature scar tissue was forming. The conclusion is made that operation early after
      trauma in combination with conservative therapy may prevent deformation and
      dystrophic changes in the cartilages as well as development of scar tissue.

PMID- 12501770
TI  - [Head and neck lymph node lesions].
AB  - In 1999-2000, puncture cytological diagnosis was made in 134 patients. Enlarged
      lymph nodes (LN) were detected in 114 patients. The enlargement occurred due to
      nonspecific inflammation (38.6%), common hyperplasia (26.3%), tuberculosis
      (18.5%), metastases of cancer (14.9%), sarcoidosis (1.7%). LN tuberculosis was a
      frequent finding in adult women--in 2/3 of all tuberculosis cases. In children it
      was rare (3.7%). LN enlargement was caused by cancer in divided by of the cases.
      LN tuberculosis was detected in adults 5 times more frequently than in children.
      M. tuberculosis were detected bacterioscopically in tuberculous lymph nodes
      puncture biopsies only in 6 examinees (28.6%). The Mantoux test appeared
      unreliable in diagnosis of peripheral LN tuberculosis. Tuberculous LN located
      under the mandible or on the neck. Specific non-tuberculous processes, primarily
      malignant tumors, were revealed in enlarged parotid and supraclavicular LN in
      half of the cases.

PMID- 12501771
TI  - [Rehabilitation of patients after laryngeal extirpation].
AB  - Current rehabilitation opportunities for patients after laryngeal extirpation are
      described. In spite of much success in such rehabilitation many patients after
      discharge from ENT hospitals experience difficulties in communication, in control
      of a new voice. Patients with removed larynx need more attention from health and
      social services.

PMID- 12501772
TI  - [Treatment of vocal fold nodules in singers].
AB  - Vocal nodules (singer's nodules) are a typical professional disease of the vocal
      apparatus. This disease occurs more frequently in 20- to 50-year-old singers. The
      nodules form because of vascular disorders secondary to overstrain of the vocal
      apparatus in phonation and disorders of vegetative innervation. 43 opera singers
      were treated whose age and singing history ranged from 22 to 57 years and 3 to 26
      years, respectively. The treatment combined psychotherapy, medicines with
      phlogenzym as a basic drug, physiotherapy and phonopedia. Phlogenzym allows to
      avoid "silence regimen", surgical intervention. This improves treatment efficacy,
      shortens the time of disability for singers.

PMID- 12501773
TI  - [Experience in the treatment of patients with chronic tonsillitis with intra
      lacunar exposure to Ni-Ag laser beam].

PMID- 12501774
TI  - [Chlamydia infections in children with acquired cicatricial laryngeal and
      tracheal stenosis].
AB  - The examination for Chlamydial infection was carried out in 49 children aged from
      1 year 10 months to 15 years (mean age 9 years 6 months +/- 3 years 8 months)
      with laryngotracheal cicatricial stenosis (CS) provoked by long nasotracheal
      intubation. Antibodies to C. pneumoniae in diagnostically significant titers were
      detected in 13 of 49 children (26.5%), to C. trachomatis--in 1 patient who had
      both infections. All the infected patients except the latter carried tracheal
      canules or were decanulated. Age of the patients with Chlamydial infection at the
      time of examination and development of CS was significantly older than of non
      infected children. No significant difference was found between these patients by
      duration of the intubation and of the disease. Consideration of the fact that 12
      of 13 children with C. pneumoniae infection carried tracheocanules suggests that
      the infection may be secondary.

PMID- 12501775
TI  - [Relationship of pathological gastroesophageal reflux and some symptoms of
      chronic laryngeal and pharyngeal inflammation].
AB  - Sixty eight patients with laryngeal and pharyngeal complaints have undergone both
      otorhinolaryngological and gastroenterological examinations. Most of the
      examinees were diagnosed to have pathological gastroesophageal reflux (PGER).
      Typical complaints for heartburn and eructation occurred in less than half the
      patients with PGER. It is proposed to conduct a gastroenterological examination
      of patients with persistent chronic inflammation of laryngeal and pharyngeal
      mucosa.

PMID- 12501776
TI  - [Ozone therapy in patients with chronic purulent frontal sinusitis].
AB  - Inflammatory diseases of the front sinuses, rather common now, run often an
      atypical complicated cpirse. 102 patients with chronic purulent frontal sinusitis
      received treatment consisting in irrigation of the paranasal sinuses with ozone
      oxygen mixture. A total of 5-7 procedures were given (one course). The control
      group of 30 patients was treated conventionally. 89% of the irrigated patients
      recovered faster than the controls.

PMID- 12501777
TI  - [The technique of non-puncture treatment of paranasal sinus inflammation using
      sinus evacuator].

PMID- 12501778
TI  - [Interpretation of leukocyte count in acute purulent otitis media in infants].
AB  - Interpretation of leukograms of 181 infants with acute otitis media purulenta
      (OMP) has shown that these patients had leukopenia in 15.5%, normal leukocyte
      count in 66.3%, leukocytosis in 6.6%, neither neutrophylesis with a left shift
      nor toxic granularity of leukocytes, neutropenia in 13.8%, neutrophylesis in 5%,
      monocytopenia in 87.8%, normal lymphocyte count in 78.6%, lymphocytopenia in
      21.2%. The leukograms of the infants with acute OMP evidence for low tension of
      normal adaptation reactions. This may help in assessment of the efficacy of on
      going treatment.

PMID- 12501779
TI  - [One-stage reconstruction of the defect of facial soft tissues with a chest graft
      in surgery of locally advanced maxillary cancer].

PMID- 12501780
TI  - [Derinat in the treatment of patients with nasal furuncle].

PMID- 12501781
TI  - [Solitary fibrous mesothelial pleural tumor in the maxillary sinus and nasal
      cavity].

PMID- 12501782
TI  - [Homeostasis of the maxillary sinus and paranasal sinusitis: current view].

PMID- 12501783
TI  - [We have passed through storms and survived].

PMID- 12501784
TI  - [Progress and efficiency of implementation of the purpose-oriented program
      "Urgent Tuberculosis Control Measures in Russia in 1998-2004" in the Urals
      Federal Region].
AB  - The paper analyzes the tuberculosis epidemic situation in the areas of the Urals
      Federal Okrug, which is regarded to be very serious. Recent years are marked by a
      rise in basic epidemiological indices, such as incidence, prevalence, spread of
      cases with bacterial isolation, mortality due to tuberculosis. There is a direct,
      close, and significant relationship of positive tuberculin tests and morbidity in
      children to the spread of tuberculosis with bacterial isolation. The
      effectiveness of tuberculosis controlling measures within the federal special
      program Urgent Tuberculosis Controlling Measures in Russia in 1998-2004 was
      evaluated and guidelines for its enhancement are stated.

PMID- 12501785
TI  - [Epidemic situation of tuberculosis in the Urals and Volga-Vyatka Regions and
      immediate tasks of the service].
AB  - There is a disease spreading trend in the development of an epidemic process in
      the past decade (1992-2001). The number of patients with active tuberculosis
      increased by 2-2.5 times. In 2001, the morbidity rate first decreased by 3% in
      both regions. In overall, the epidemic situation is regarded as tense. The
      greatest priorities of work under the conditions of these regions are given.
      Emphasis is laid on that regional tuberculosis controlling programmes should be
      financially supported.

PMID- 12501786
TI  - [Epidemiological features of the pathomorphism of infiltrative pulmonary
      tuberculosis in the Perm Region].
AB  - The time course of changes in current epidemiological indices and epidemically
      significant features of the pathomorphism of infiltrative pulmonary tuberculosis
      in those living in the Perm Region are mainly characterized by negative trends.
      They lie in the increase or stable maintenance of high rates of morbidity,
      mortality, and destructive pattern of a lesion accompanied by bacterial
      isolation. The reason for the established situation is incomplete realization of
      potentialities of improving actions to detect the disease early, to optimize
      diagnosis and medical therapy, and to considerably expand an phthisiosurgical
      aid.

PMID- 12501787
TI  - [A sociomedical portrait of tuberculosis control service workers].
AB  - The social and medical causes of occupational tuberculosis were analyzed by using
      the results of questionnaire surveys in 300 workers of tuberculosis controlling
      service. Low salaries, high working load, unbalanced nutrition, poor
      rehabilitation on vacation are the most important risk factors leading to high
      rates of both somatic and occupational morbidity in the staff of antituberculosis
      service.

PMID- 12501788
TI  - [Medicosocial structure and cause of death of patients with tuberculosis].
AB  - Tuberculosis mortality rates increased in the Kirov Region during 1990-200, but
      remained lower than those in Russia. In the past 2 years, the mortality became
      stable. The sociomedical structure and the causes of death were studied in 62
      patients with tuberculosis who had died in the hospital of the Kirov regional
      tuberculosis dispensary in 2000-2001. An analysis was made among new cases and
      cases registered at the dispensary. Deaths more commonly occurred in males
      (83.8%), able-bodied and poor individuals (75.8 and 61.3%, respectively),
      patients with acutely progressive pulmonary tuberculosis (53.2%), and those with
      drug resistance (48.4%). Tuberculosis progression was the main cause of death in
      53.2%.

PMID- 12501789
TI  - [Treatment of patients with destructive pulmonary tuberculosis with concomitant
      diabetes mellitus].
AB  - Diabetes mellitus accompanying tuberculosis complicates the course of the latter
      and remains a topical problem of phthisiology. Surgical treatment of patient with
      both conditions presents a high risk and is employed unreasonably rarely. The
      results of medical (173 patients) and surgical (107 patients) treatments were
      studied in patients with destructive tuberculosis concurrent with diabetes
      mellitus. Analyzing early and late results of treatment showed a more steady
      state effect in the group of surgically treated patients. Thus, surgery should be
      desirably used in all patients with preserving destructive changes after the
      basic course of antibacterial therapy.

PMID- 12501790
TI  - [Clinical picture and treatment of tuberculosis in HIV-infected patients].
AB  - In the Orenburg Region, HIV-infected individuals fall ill with tuberculosis tens
      time more frequently than uninfected ones. Thirty five HIV-infected patients with
      tuberculosis and 32 patients without immunodeficiency (a control group) were
      examined and treated. Of the clinical forms of tuberculosis, infiltrative
      tuberculosis was predominant, tissue destruction being seen in half the cases.
      Extrapulmonary tuberculosis was revealed in 11.4% of the patients. Multidrug
      resistance was ascertained in 20% of cases. The efficiency of treatment in
      patients with double HIV/tuberculosis infection was 10-15% lower than that in
      those without HIV infection.

PMID- 12501791
TI  - [Diagnostic value of bacterial isolation in destructive pulmonary tuberculosis].

PMID- 12501792
TI  - [Optimization of indirect endolymphatic injection of isoniazid in pulmonary
      tuberculosis].
AB  - The authors have substantiated and studied the use of lymphotropic (interstitial)
      injection of 1% isoniazid solution in the complex therapy of patients with
      pulmonary tuberculosis. The method provides active interstitial functioning of
      the diseased organ. This leads to a substantial improvement of immediate results
      of treatment in patients as accelerated closure of decay cavities and double
      cessation of bacterial isolation.

PMID- 12501793
TI  - [Prospects of the use of adaptogenic amino acids in the pathogenetic therapy of a
      number of pathologic states].

PMID- 12501794
TI  - [Surgical policy in tuberculous pleurisy].
AB  - Two hundred and eighty seven cases of tuberculous pleurisy are analyzed.
      According to the pleural contents, four phases of development of this disease are
      identified. These include: 1) free pleurisy; 2) partially encysted pleurisy; 3)
      encysted pleurisy, and 4) adhesive pleurisy. An algorithm of use of draining
      procedures and surgical interventions depending on the phase of pleurisy is
      proposed. Among other things, indications for thoracoscopy that was performed in
      66 patients with tuberculous pleurisy for its therapy were stated. Thoracoscopy
      is ineffective in adhesive pleurisy, in the presence of a rigid residual cavity
      in particular, and thus preference should be given to thoracotomy with
      pleurectomy and decortication of the lung. This operation was made in 39 cases.
      Timely use of draining procedures and surgical interventions make it possible to
      achieve recovery from tuberculous pleurisy over shorter periods of time and with
      minimal residual changes.

PMID- 12501795
TI  - [Efficiency of extrapleural thoracoplasty in pulmonary tuberculosis].
AB  - Under the present conditions, to improve surgical collapse techniques and to
      popularize their are a pressing task of phthisiology. Of 23,902 thoracic
      interventions made in the regional tuberculosis dispensary during 50 years, 1782
      cases thoracoplasties were performed. By modifying the procedure of posterior
      upper extrapleural thoracoplasty, the authors could expand its use in patients
      with low functional reserves, including in those with bilateral destructive
      lesions. Promising results of its use in generalized destructive tuberculosis
      make extrapleural thoracoplasty the operation of choice in a great deal of
      patients.

PMID- 12501796
TI  - [Clinical picture and differential diagnosis of anterior granulomatous uveitis].
AB  - Nineteen patients with anterior endogenous granulomatous uveitis were examined.
      Tuberculous and sarcoidosal anterior uveites run by and large similarly, but have
      some differences. Valid etiological diagnosis of granulomatous uveites requires a
      complex approach with consideration of extraocular manifestations.

PMID- 12501797
TI  - [Neuro-orthopedic approach to the treatment of tuberculous spondylitis].
AB  - The results of treatment in 50 patients with tuberculosis of the thoracic and
      lumbar spine are presented. The routine surgical treatment was used in 32 cases.
      In 11 patients, the use of an extrafocal external fixation apparatus made it
      possible to achieve the axis and height of the diseased portion of the vertebral
      column and to start early postoperative activation.

PMID- 12501798
TI  - [Clinical presentation and course of sarcoidosis under the conditions of the West
      Urals].
AB  - The specific features of the clinical presentation and course of respiratory
      sarcoidosis (S) and the efficiency of its treatment were studied in 109 new cases
      in the Perm Region. The incidence of S is higher among residents from towns with
      developed heavy industry, mainly in females. Primary chronic S was predominant
      (89.9%). The efficiency of treatment in the patients was 69.5%. The results of
      treatment were worse in the untimely detection of S. The recovery rates were
      higher with corticosteroid tablets used continuously (87.5%) and those were lower
      with their intermittent use (82.9%).

PMID- 12501799
TI  - [Pathogenetic mechanisms of action of tarry substances and Mycobacterium
      tuberculosis in guinea pigs and rats].
AB  - Harmful environmental agents [polycyclic aromatic hydrocarbons (PAH)] have been
      ascertained to greatly stimulate the biosynthesis of arginine and urea and reduce
      the amount of sulfur-containing metabolites in the liver of experimental animals
      by increasing the level of sulfur sulfate. Against this background, contamination
      with Mycobacteria tuberculosis (MBT) inhibits the activity of arginine and
      drastically decreases its amount by elevating the concentration of sulfur
      containing metabolites. The supplementary administration of sodium glutamate to
      animals receiving PAH and MBT potentiates a decrease in nitrogen-rich metabolites
      and increases the level of sulfur-containing metabolites guinea pigs,
      tuberculosis resistance being on the rise. Under the influence of a combined
      action of PAH and MBT, the mutagenic effect of the former lowered in rats.

PMID- 12501800
TI  - [Prognostic value of isolation of L-forms of Mycobacterium tuberculosis].
AB  - A procedure has been developed to detect antilysozymatic activity n L forms of
      Mycobacterium tuberculosis (MBT). A mode of predicting the course of a
      tuberculosis process in the lungs by the degree of antilysozymatic activity of
      MBT is outlined. Thus, when the level is 4 micrograms/ml or higher, progression
      or exacerbation of tuberculosis is predicted, when that of 0-3 micrograms/ml, a
      good prognosis is expected.

PMID- 12501801
TI  - [Biochemical parameters of BALF in the differential diagnosis of infiltrative
      tuberculosis and pneumonia].

PMID- 12501802
TI  - [Radiologic studies in the diagnosis of pulmonary tuberculosis].

PMID- 12501803
TI  - [Training of physicians-phthisiologists in the Urals Federal Region].
AB  - The paper analyzes problems associated with the training and retraining of staff
      for phthisiological service and general practitioners, such as therapists and
      pediatricians, in the timely diagnosis of tuberculosis. The authors share their
      experience in organizing the training of physicians in antituberculosis aspects.
      Interaction of departments of tuberculosis and a regional research institute of
      phthisiopulmonology and the use of current educational technologies are required
      to enhance the efficiency of this work.

PMID- 12501804
TI  - [Military sanatorium "Chemitokvadzhe"--Black Sea health resort of the Military
      Air Force].

PMID- 12501805
TI  - Regional Health Information Networks and telematics applications in a user
      friendly information society.

PMID- 12501806
TI  - Patient acceptance of educational voice messages: a review of controlled clinical
      studies.
AB  - OBJECTIVES: The objective of this study was to evaluate controlled evidence on
      the impact of automated computer-based telephone messaging technology upon health
      outcomes, cost savings and acceptance by patients, caregivers and care providers.
      METHODS: Systematic searches of electronic databases were conducted to find
      controlled clinical studies of automated phone messaging used in patient care.
      Studies were selected based on the three criteria: 1) randomized controlled
      trials or controlled trials; 2) patients receiving health care related education,
      information, advice or reminder for a specific action to be taken in their home
      setting; and 3) use of automated computer-based phone technology to deliver the
      messages. Information abstracted from studies included information about the
      institution, persons targeted, intervention and its effect on health outcomes,
      costs and acceptance by patients and caregivers. RESULTS: A total of nineteen
      studies were identified for review. Sixteen studies were randomized controlled
      trials and three were controlled studies with no randomization. Studies were
      placed in two categories, preventive care education and chronic care studies.
      Preventive care education studies covered childhood immunizations, medication
      compliance, influenza vaccinations, tuberculosis and health prevention activities
      and chronic care studies were related to cholesterol, diabetes, hypertension and
      congestive heart failure. More than 80% of studies showed significant impact upon
      measurable health outcomes. CONCLUSIONS: Controlled evidence substantiates the
      efficacy of automated telephone communication in improving the quality of care.
      Educational voice messages are acceptable in patients and represent an important
      opportunity to enhance telemedicine and telehealth applications.

PMID- 12501807
TI  - User friendliness aspects of home care telematics.
AB  - OBJECTIVES: Asthma is the most common chronic childhood disease with a high
      number of admissions and emergency room visits in pediatric hospitals. Treatment
      of asthmatic patients is best done by asthma specialists and requires the chronic
      use of prophylactic medications, additional treatment for acute exacerbations and
      regular check-ups. In Crete, a Greek island, there are many children with asthma
      who are not receiving care by an asthma specialist. The only specialty clinic for
      asthmatic children in Crete is in Heraklion, a city in the center of the island.
      We attempted to use telemedicine in order to reach and follow children with
      asthma who live in distant areas in Crete. METHODS: We set up a pilot
      telemedicine program with 10 asthmatic children already followed at the Specialty
      Clinic. Using teleconferencing techniques, we were able to obtain the medical
      history, examine the patients, educate them about the disease and adjust the
      treatment. RESULTS: The parents of patients accepted the telemedicine service
      with a percentage of 90% and showed a special interest in this new service.
      CONCLUSIONS: We conclude that telemedicine for asthmatic children performed by
      their specialist is feasible and accepted by the majority of patients.

PMID- 12501808
TI  - Healthcare telematic applications in Cyprus.
AB  - OBJECTIVES: a) To present a review of ongoing health telematic applications in
      Cyprus. b) To promote the use of these health telematic applications in the
      Cyprus region. c) To help in the spin off of other health telematic applications
      thus enabling the offering of a better health service to the citizens. METHODS
      AND RESULTS: The health telematics applications include a medical system for
      emergency telemedicine (AMBULANCE and EMERGENCY-112 projects), a system for the
      evaluation of the risk of stroke by telemedicine (EROS), a diagnostic
      telepathology network in gynaecological cancer (TELEGYN), a collaborative virtual
      medical team for home healthcare of cancer patients (DITIS), and a health
      telematics training network (HEALTHNET). The paper refers to the set-up and
      characteristics of these applications and tries to relate them with the health
      policies that should be applied in Cyprus. CONCLUSIONS: It is anticipated that
      this paper will promote the importance of health telematics applications for
      Cyprus and increase the awareness on the possibilities that these applications
      offer for health policies in all levels of health related human resources.

PMID- 12501809
TI  - Tele-affiliation in medical education: experience from the international program
      at Yale Office of Telemedicine.
AB  - OBJECTIVES: Telemedicine is developed in response to the needs of users that
      results in a more viable model. Yale has developed a process called tele
      affiliation to combine services that are customized to the international client's
      needs. METHODS: Several defined steps compose the tele-affiliation process. The
      Yale-Greece telemedicine program is used as an illustration of this process. Some
      of the programs developed in response to Greek needs include breast cancer
      clinics, women's health clinics and tele-homecare monitoring for post-operative
      and chronically ill patients. RESULTS: Tele-affiliation creates on infrastructure
      that has the potential to change the method of health care delivery. By using the
      infrastructure created by the tele-affiliation process, templates for disease
      management, as well as health promotion and education can be delivered to a
      global audience. CONCLUSIONS: A tele-affiliation education environment has been
      developed and tested between Yale University School of Medicine and Greece
      resulting in an improved infrastructure for health education and management.

PMID- 12501810
TI  - Development of a regional health care network and the effect of knowledge
      intensive work on personnel and organisation.
AB  - OBJECTIVES: a) To present a regional health care communication system developed
      in the North Karelia Hospital District with the help of two EU funded information
      technology projects namely the TERVE project (1) which was implemented at the
      national level financed by the regional subsidy 6 of the ERDF and the CHIN
      project (2) that was implemented at the European level. b) To present the
      questions and issues that arose when implementing new technologies in a regional
      health care environment. RESULTS: Transformations in information technology are
      usually parts of other organisational transformations in health care. As a result
      of these issues, implementation of great information technology transformations
      has failed because of too strong a technology emphasis, insufficient
      participative touch and underestimation of social factors. Another result is that
      there is a cultural shock for physicians working in organisations where there are
      networks rather than hierarchies and relationships are predominantly contractual
      rather than professional. CONCLUSIONS: The effectiveness, productivity and
      profitability of the hospitals will be decisively dependent on information
      technology as well as its regional applications. Transformations in information
      technology are parts of other organisational transformations in health care, and
      can induce cultural shocks for physicians since the networked environment has a
      different philosophy than the hierarchy-based environment which was the case
      until recently. Finally, in a taxation based system, one key requirement is to
      understand that the network contacts and the time spent on networks must bring
      additional value to health care.

PMID- 12501811
TI  - Information technology can enhance quality in regional health delivery.
AB  - OBJECTIVES: a) The use of information technology (IT) based solutions for quality
      health delivery in regional health information networks and the study of the
      enabling factors for their use in a regional health care network from key classes
      of users such as the medical personnel and the citizens. b) Identification of
      potential technologies for usage from all citizens and health providers in a
      regional environment, in all aspects of everyday life. c) Presentation of a
      generic user model for reference when developing and assessing IT based health
      delivery solutions. METHODS: After defining the major questions to be addressed,
      an overview of tele-health and tele-medicine technologies and solutions currently
      available shall be presented. Further, a generic user model applied to the use of
      IT based regional health delivery solutions both for the daily life and home
      care, and for research and clinical routine purposes are presented. Enabling
      technologies for integration of different IT modules, medical data processing and
      management procedures and the wireless application protocol (WAP) technology is
      discussed. RESULTS: Different levels of user applications are presented such as
      mobile telephony driven health information monitoring and systems integrating
      electronic health care records with multimedia medical information management and
      processing modules. CONCLUSIONS: Although IT solutions are advanced and continue
      to evolve, still the user acceptance and user friendliness issues are unresolved.
      Mobile telecommunication solutions however may hold the key for wide scale
      implementation of IT solutions in regional health information networks and
      increased quality of health services.

PMID- 12501812
TI  - Extensions to the HISA standard--the SynEx computing environment.
AB  - OBJECTIVES: This paper reports on the integration work required to support the
      delivery of healthcare. Specifically, four elements are included being: the DHE
      (a standards based distributed healthcare environment), Synapses which is a
      patient record server, XML as a technology to deliver records, and finally two
      client applications that facilitate structured data entry (SDE) and the remote
      booking of specialist services. METHODS: A general motivation for the work is
      presented and augmented on hand of a clinical scenario. Additionally, the
      adoption of a middleware approach is reviewed. The role of computerised patient
      records is described followed by an account of a federated record server. The
      approach favoured by standards bodies in utilising XML is covered and the
      tailoring to suit the needs of the integration is explained. The main practical
      challenges in achieving integration are presented, one of these being the mapping
      between the DHE data model and the Synapses server record architecture. RESULTS:
      The described environment has been demonstrated to provide the functionality that
      is required and in addition it has been shown that the engineering challenges can
      be met in a controlled and orderly manner. CONCLUSIONS: The role of the DHE
      middleware component acting as an 'anchor' has been shown to be a valid one onto
      which other specialised components can be added to provide a richer service
      environment. Additionally, it has been demonstrated that XML is a good candidate
      technology that facilitates connectivity to client applications over an extranet.
      The demands inherent in both the clinical scenario and the computerised patient
      record can be met by the computing environment described in the paper.

PMID- 12501813
TI  - World-Wide Web-based graphical user interfaces for laboratory data.
AB  - OBJECTIVES: Electronic medical record systems permit collection of large amounts
      of medical information. Usually, information is presented in a fixed format,
      either as text or tables. Health care providers have to navigate this fixed
      format in order to find information useful for a specific patient-provider
      interaction. The main objective of this work was to allow the provider immediate
      access to specific laboratory information through the development of a highly
      customizable, graphical user interface to the Mayo Clinic laboratory information
      system. METHODS:  RESULTS: Here we describe this platform-independent, World-Wide
      Web-based graphical user interface that allows the provider to see all or a
      predetermined panel of essential laboratory data in graphical format. Advantages
      include availability at internet-based workstations, immediate recognition of
      trends over time, ability to zoom in and out of specific periods of time, and
      detailed analysis of patient values in relationship to normal values.
      CONCLUSIONS: Web browser-based user interface allowing graphical display of
      laboratory data using Java technology was described. The connection to the Mayo
      Clinic laboratory information system combines cross-platform support for use on
      virtually any networked machine, interaction through a Web browser for ease of
      use, and a combination of the Perl and Java languages for powerful data
      processing and interactivity.

PMID- 12501814
TI  - Developing a Public Key Infrastructure for a secure regional e-Health
      environment.
AB  - OBJECTIVES: Internet technologies provide an attractive infrastructure for
      efficient and low cost communications in regional health information networks.
      The advantages provided by the Internet come however with a significantly greater
      element of risk to the confidentiality and integrity of information. This is
      because the Internet has been designed primarily to optimize information sharing
      and interoperability, not security. The main objective of this paper is to
      propose the exploitation of public-key cryptography techniques to provide
      adequate security to enable secure healthcare Internet applications. METHODS:
      Public-key cryptography techniques can provide the needed security infrastructure
      in regional health networks. In the regional health-care security framework
      presented in this paper, we propose the use of state-of-art Public Key
      Infrastructure (PKI) technology. Such on e-Health PKI consists of regional
      certification authorities that are implemented within the central hospitals of
      each region and provide their services to the rest of the healthcare
      establishments of the same region. RESULTS: Significant experience in this area
      has been gained from the implementation of the PKI@AUTH project. CONCLUSIONS: The
      developed PKI infrastructure already successfully provides its security services
      to the AHEPA university hospital. The same infrastructure is designed to easily
      support a number of hospitals participating in a regional health information
      network.

PMID- 12501815
TI  - Networking in shared care--first steps towards a shared electronic patient record
      for cancer patients.
AB  - OBJECTIVES: This paper aims at identifying the data protection and security
      requirements for a cross-institutional EPR. Three possible models and the first
      steps towards a cross-institutional EPR for the Thoraxklinik Heidelberg and the
      Department of Clinical Radiology of the University Medical Center of Heidelberg
      shall be discussed. METHODS: A comprehensive analysis of literature and legal
      documents supplied information for determining the data protection and security
      requirements. By means of information system analysis, the technical
      preconditions in both institutions as well as three possible models towards a
      cross-institutional EPR were identified. RESULTS: According to the German penal
      code it is only allowed to reveal patient information to external physicians in
      cases of so-called "treatment connection". An extension of the written consent,
      signed by the patient, verifying the patient agreement that his/her patient data
      will be stored in a cross-institutional EPR is needed. Among the three models
      that we identified, the model that constitutes of a virtual EPR with distributed
      data capture in both institutions was favored. By means of SecuRemote software a
      secure connection between the Thoraxklinik Heidelberg and the Department of
      Clinical Radiology was established, allowing the physicians to view the complete
      cross-institutional health information of a jointly treated patient during the
      weekly consultation on radiotherapy. CONCLUSIONS: Many requirements listed in
      this paper are requirements for electronic patient records in general. Besides
      these general requirements there are specific requirements for a cross
      institutional EPR. The legal situation in Germany complicates the development and
      implementation of a cross-institutional EPR. However, we think that the efforts
      are reasonable, because a cross-institutional EPR will be able to improve the
      communication between health institutions, medical disciplines and persons
      involved in shared care processes. It provides them with more complete health
      information about the jointly treated patients. A cross-institutional EPR is,
      therefore, expected to improve the quality of patient care.

PMID- 12501816
TI  - Heuristics for identification of acronym-definition patterns within text: towards
      an automated construction of comprehensive acronym-definition dictionaries.
AB  - OBJECTIVES: To develop an automated, accurate and scalable method by which
      acronym-definition pairs can be identified within text. Its primary advantage is
      in enabling information processing methods to resolve author-defined acronyms,
      but it also allows an automated creation of a reference work on acronym
      definitions. This has several advantages over manual or semi-automated methods,
      besides time and effort saved, such as enabling identification of relative
      frequencies for alternate acronyms and definitions as well as spelling, phrasing
      and hyphenation variants for a unique acronym-definition pair. It also aids users
      in identifying acronym/definition variants present in the literature that may not
      necessarily be in biomedical databases. METHODS: A set of heuristics to
      accurately locate and identify the boundaries of acronym-definition pairs was
      developed and refined in terms of precision and recall on subsets of MEDLINE
      records. These training sets were gradually increased in size and heuristics re
      evaluated to ensure scalability. RESULTS: Our final set of Acronym Resolving
      General Heuristics (ARGH) had a sample-based estimated rate of 96.5 +/- 0.4%
      precision and 93.0 +/- 2.7% recall when tested on over 12 million MEDLINE
      records, identifying more than 174,000 unique acronyms and their 737,000
      associated definitions. CONCLUSIONS: We estimate that as much as 36% of the
      acronyms in MEDLINE are associated with more than one definition and, conversely,
      up to 10% of definitions are associated with more than one acronym. The number of
      unique acronyms in MEDLINE is increasing at a rate of approximately 11,000 per
      year, while the number of definitions associated with them is growing at
      approximately four times that rate. Access to the ARGH database is available
      online at http://lethargy.swmed.edu/ARGH/argh.asp. The heuristic module and
      database are available upon request.

PMID- 12501817
TI  - Development and implementation of computerized clinical guidelines: barriers and
      solutions.
AB  - Research indicates that computerized decision support systems (CDSSs) can improve
      clinical performance and patient outcomes, and yet CDSSs are not in widespread
      use. Physician guidelines, in general, face barriers in implementation.
      Guidelines in a computerized format can overcome some of the barriers to
      conventional text-form guidelines; however, computerized programs have novel
      aspects that have to be considered, aspects such as technical problems/support
      and user interface issues that can act as barriers. Though the literature points
      out that human, organizational, and technical issues can act as barriers in the
      implementation of CDSSs, studies clearly indicate that there are methods that can
      overcome these barriers and improve CDSS acceptance and use. These methods come
      from lessons learned from a variety of CDSS implementation ventures. Notably,
      most of the methods that improve acceptance and use of a CDSS require feedback
      and involvement of end-users. Measuring and addressing physician or user
      attitudes toward the computerized support system has been shown to be important
      in the successful implementation of a CDSS. This article discusses: 1) the
      barriers of implementation of guidelines in general and of CDSSs; 2) the
      importance of the physician's role in development, implementation, and adherence;
      3) methods that can improve CDSS acceptance and use; and 4) the types of tools
      needed to obtain end-user feedback.

PMID- 12501818
TI  - Cortical source estimate of combined high resolution EEG and fMRI data related to
      voluntary movements.
AB  - OBJECTIVES: In this paper, we employed advanced methods for the modeling of human
      cortical activity related to voluntary right one-digit movements from combined
      high-resolution electroencepholography (EEG) and functional magnetic resonance
      imaging (fMRI). METHODS: Multimodal integration between EEG and fMRI data was
      performed by using realistic head models, a large number of scalp electrodes
      (128) and the estimation of current density strengths by linear inverse
      estimation. RESULTS: Increasing of spatial details of the estimated cortical
      density distributions has been detected by using the proposed integration method
      with respect to the estimation using EEG data alone. CONCLUSION: The proposed
      method of multimodal EEG-fMRI data is useful to increase spatial resolution of
      movement-related potentials and can also be applied to other kinds of event
      related potentials.

PMID- 12501819
TI  - Side effects. The usual suspects.

PMID- 12501820
TI  - A brief history of HIV drug therapy.

PMID- 12501821
TI  - Strange side effects.

PMID- 12501822
TI  - Focus on fat.

PMID- 12501823
TI  - Lots of volunteers needed.

PMID- 12501824
TI  - Lactic acid and nuke damage.

PMID- 12501825
TI  - No nukes please.

PMID- 12501826
TI  - Fat wasting--AZT vs. d4T.

PMID- 12501827
TI  - Sugar blues.

PMID- 12501828
TI  - Predicting body shape changes.

PMID- 12501829
TI  - Niacin for high triglycerides.

PMID- 12501830
TI  - Supplement fix for nelfinavir-related diarrhea.

PMID- 12501831
TI  - AHA medical/scientific statement. 1994 revisions to classification of functional
      capacity and objective assessment of patients with diseases of the heart.

PMID- 12501832
TI  - Functional foods: scientific and global perspectives.

PMID- 12501833
TI  - Bibliography. Current world literature. Neoplasms.

PMID- 12501834
TI  - Bibliography. Current world literature. Trauma and rehabilitation.

PMID- 12501835
TI  - Current awareness in human psychopharmacology.

PMID- 12501836
TI  - Bibliography. Current world literature. Metabolic disorders and neurotoxicology.

PMID- 12501838
TI  - Current awareness in human psychopharmacology.

PMID- 12501837
TI  - Frank A. Beach Award: Parenting--the other reproductive behavior.

PMID- 12501839
TI  - Genetic discrimination. Why Congress must ban genetic testing in the workplace.

PMID- 12501840
TI  - Physician-assisted suicide permits dignity in dying. Oregon takes on attorney
      general Ashcroft.

PMID- 12501842
TI  - Spotlight. Physician practice management systems.

PMID- 12501841
TI  - Supreme court redefines disability. Limiting ADA protections for cochlear
      implantees in hospitals.

PMID- 12501843
TI  - A look back at the London smog of 1952 and the half century since.

PMID- 12501844
TI  - A half century later: recollections of the London fog.

PMID- 12501845
TI  - Jumpstarting DNA repair.

PMID- 12501846
TI  - Minimally invasive bypass surgery.

PMID- 12501847
TI  - Rice and rice blast: new bases for comparison.

PMID- 12501848
TI  - Minimally invasive bypass surgery.

PMID- 12501849
TI  - Minimally invasive bypass surgery.

PMID- 12501850
TI  - Minimally invasive bypass surgery.

PMID- 12501851
TI  - Smoking inflames joints.

PMID- 12501852
TI  - Two committees tackle toxicogenomics.

PMID- 12501853
TI  - Fifty years later: clearing the air over the London smog.

PMID- 12501854
TI  - Regression of splenic lymphoma after treatment of hepatitis C virus infection.

PMID- 12501855
TI  - Regression of splenic lymphoma after treatment of hepatitis C virus infection.

PMID- 12501856
TI  - Cadmium cause and effect. Looking at renal function.

PMID- 12501857
TI  - Bringing home more than a paycheck. Workers and pesticides.

PMID- 12501858
TI  - Accurate prediction of fulminant hepatic failure in severe acute viral hepatitis:
      multicenter study.
AB  - BACKGROUND: We have attempted to predict the development of fulminant hepatic
      failure at the stage of severe acute hepatitis before the onset of coma. This
      prediction is valuable because it may be used to block the development of
      fulminant hepatic failure with appropriate medical treatment. METHODS: To
      establish a discrimination formula, we retrospectively compared 13 clinical and
      laboratory variables in 36 patients with acute viral hepatitis and prothrombin
      levels of 40% or less of the control value who later developed fulminant hepatic
      failure with these variables in 12 patients who recovered spontaneously. A
      prospective study of 58 patients who developed fulminant hepatic failure and 18
      who spontaneously recovered confirmed the validity of this formula. RESULTS: In
      the retrospective study,we established the following discrimination equation: Z =
      -0.89 + 1.74 x (causal viruses, 1 point for type A or type B in acute hepatitis B
      virus [HBV] infection, 2 points for others) + 0.056 x (total bilirubin, mg/dl)
      0.014 x (cholinesterase, U/ml). A positive Z value indicates that fulminant
      hepatic failure will develop. In the prospective study, the specificity,
      sensitivity, predictive accuracy, and positive and negative predictive values
      were 0.833, 0.983, 0.947, 0.950, and 0.938, respectively. CONCLUSIONS: The
      present study indicated that fulminant hepatic failure can be predicted, by a
      simple discrimination equation, at the stage of severe acute hepatitis.

PMID- 12501859
TI  - Radical and simple mastectomy.

PMID- 12501860
TI  - Radical and simple mastectomy.

PMID- 12501861
TI  - Radical and simple mastectomy.

PMID- 12501862
TI  - Thrombotic microangiopathies.

PMID- 12501863
TI  - 62nd annual meetings of the American Conference of Governmental Industrial
      Hygienists and the American Industrial Hygiene Association.

PMID- 12501864
TI  - EMRs and elephants.

PMID- 12501865
TI  - Suspected choledocholithiasis: EUS, magnetic resonance cholangiopancreatography,
      or intraoperative cholecystectomy?

PMID- 12501866
TI  - Honoring the unwritten contract.

PMID- 12501867
TI  - ACOG practice bulletin. Selective estrogen receptor modulators. Number 39,
      October 2002 (replaces Committee Opinion Number 224, October 1999).
AB  - Selective estrogen receptor modulators (SERMs) are synthetic compounds that bind
      estrogen receptors and produce agonistic activity in some tissues while acting as
      estrogen antagonists in other tissues. Although referred to collectively, their
      effects in different organs (eg, endometrium, urinary tract) are far from
      uniform. Much confusion exists about the indications for their use and the
      effects of these compounds. The purpose of this document is to review the use of
      SERMs for breast cancer risk reduction and skeletal protection as approved by the
      U.S. Food and Drug Administration (FDA).

PMID- 12501868
TI  - ACOG committee opinion. Safety of Lovenox in pregnancy. Number 276, October 2002.
      Committee on Obstetric Practice.
AB  - Lovenox (enoxaparin sodium) therapy appears to be safe and efficacious for
      pregnant women who are candidates for either prophylactic or therapeutic heparin.
      However, the use of enoxaparin and other low-molecular-weight heparins for
      therapeutic anticoagulation is not recommended for pregnant women with prosthetic
      heart valves. Additionally, enoxaparin should be used with caution or
      discontinued before administration of epidural for pain relief during labor.

PMID- 12501869
TI  - [Paradoxical effects of bupropion: a case report].

PMID- 12501870
TI  - Immunogenicity of therapeutic proteins: clinical implications and future
      prospects.
AB  - BACKGROUND: Therapeutic proteins have revolutionized the treatment of many
      diseases. In the near future, many more therapeutic proteins are likely to become
      available for an increasingly wide range of indications. OBJECTIVES: This article
      reviews the incidence, causes, and consequences of formation of antibodies to
      therapeutic proteins and suggests ways to address issues surrounding
      immunogenicity. METHODS: Searches of MEDLINE and EMBASE databases were performed,
      covering the period 1990 to May 2002. Search terms included immunogenicity,
      antibodies, and the names of specific therapeutic proteins and classes of
      therapeutic proteins. Bibliographies of retrieved articles were not searched.
      RESULTS: All exogenous proteins, including therapeutic ones, have the potential
      to cause antibody formation. The reported incidence of antibody formation with
      therapeutic proteins varies widely between proteins and between studies
      (depending on the assay techniques used). The clinical consequences of antibody
      formation vary with the type of antibody present; for example, neutralizing
      antibodies are more likely to cause loss of efficacy than nonneutralizing
      antibodies. The immunogenicity of therapeutic proteins can be influenced by many
      factors, including the genetic background of the patient, the type of disease,
      the type of protein (human or nonhuman), the presence of conjugates or fragments,
      the route of administration, dose frequency, and duration of treatment.
      Manufacturing, handling, and storage can introduce contaminants, or alter the 3
      dimensional structure of the protein via oxidation or aggregate formation.
      Various means have been suggested by which therapeutic proteins might be modified
      to reduce their immunogenicity, including PEGylation, site-specific mutagenesis,
      exon shuffling, and humanization of monoclonal antibodies. In the future, it may
      even be possible to predict the immunogenicity of new therapeutic proteins more
      accurately, using specifically designed animal models, including nonhuman
      primates and transgenic mice. CONCLUSIONS: Scientists and clinicians are becoming
      increasingly aware of the importance of assessing the immunogenicity of new
      molecules as they are introduced, and of existing molecules whenever they are
      modified or their manufacturing process is changed. Immune responses to
      therapeutic proteins are usually only of clinical significance if they are
      associated with the development of treatment resistance. Although various means
      to reduce the immunogenicity of therapeutic proteins have been suggested,
      monitoring for antibodies during clinical trials and postmarketing surveillance
      remains an important issue for all therapeutic proteins.

PMID- 12501871
TI  - Pharmacologic management of diabetic nephropathy.
AB  - BACKGROUND: Diabetes mellitus and hypertension are leading causes of end stage
      renal disease in the United States. Drug therapy that focuses on tight glycemic
      control and blood pressure control reduces the progression of nephropathy and
      cardiovascular complications. Angiotensin-converting enzyme (ACE) inhibitors have
      been shown to reduce the progression of renal disease in patients with diabetes.
      The angiotensin II receptor blockers (ARBs) losartan and irbesartan have also
      been shown to reduce microalbuminuria compared with placebo. The
      nondihydropyridine calcium channel blockers (CCBs) verapamil and diltiazem have
      been shown to be as effective as an ACE inhibitor in reducing urinary albumin
      excretion. OBJECTIVE: This paper reviews the pathophysiology and diagnosis of
      diabetic nephropathy and recent clinical trials assessing the most appropriate
      therapeutic options for delaying the progression of nephropathy in patients with
      diabetes. METHODS: Primary and review articles that addressed the
      pathophysiology, diagnosis, and therapeutic options for attenuating the
      progression of diabetic nephropathy were retrieved through a MEDLINE search
      (January 1990 to August 2002) and the bibliographies of identified articles were
      reviewed. English-language sources were searched using the following search
      terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, and ARBs.
      Studies published in peer-reviewed journals that were determined to be
      methodologically sound, with appropriate statistical analysis of the results,
      were selected for inclusion in this review. RESULTS: Patients with type 1
      diabetes mellitus and evidence of nephropathy should be started on an ACE
      inhibitor unless contraindicated. The ARBs and ACE inhibitors are viable choices
      for patients with type 2 diabetes mellitus and evidence of proteinuria. Patients
      who experience adverse events such as dry cough with ACE inhibitors can be
      switched to ARBs. Clinical literature suggests that if monotherapy with an ACE
      inhibitor or ARB does not provide an adequate response, a nondihydropyridine CCB
      should be added to the regimen. Nondihydropyridine CCBs should also be considered
      when ACE inhibitors and ARBs are contraindicated. CONCLUSIONS: ACE inhibitors and
      ARBs should be considered first-line therapy for patients with type 2 diabetes
      mellitus and nephropathy. The ACE inhibitors are still the drug of choice for
      patients with type 1 diabetes mellitus and evidence of incipient or overt
      nephropathy. If therapeutic goals are not achieved with an ACE inhibitor or ARB,
      then the addition of a nondihydropyridine CCB should be considered.

PMID- 12501872
TI  - Fondaparinux: a new antithrombotic agent.
AB  - BACKGROUND: Venous thrombosis is usually triggered by a low-flow state, as in
      prolonged periods of bed rest after hip or knee surgery. Antithrombotic agents
      are the drugs of choice in such circumstances. The new factor Xa inhibitor
      fondaparinux has been approved by the US Food and Drug Administration for the
      prevention of venous thromboembolism in patients undergoing hip fracture surgery,
      hip replacement surgery, or knee replacement surgery. OBJECTIVE: The aim of this
      article was to review the clinical pharmacology of fondaparinux and summarize the
      data from available clinical trials of this agent. METHODS: The terms
      fondaparinux, SR90107A/ORG31540, and factor Xa were used to search MEDLINE and
      Current Contents/Clinical Medicine for English-language studies in humans
      published between 1996 and May 2002. Unpublished data were provided by the
      manufacturer of fondaparinux, and additional information was obtained from
      abstracts presented at the 2001 congress of the International Society on
      Thrombosis and Haemostasis in Paris. RESULTS: Fondaparinux is a synthetic
      pentasaccharide that selectively binds to antithrombin III, inducing a
      conformational change that increases anti-factor Xa activity. Phase III studies
      to date have reported that fondaparinux had greater efficacy compared with
      enoxaparin in terms of prevention of venous thromboembolism after hip or knee
      replacement surgery. Preliminary studies have suggested that this agent may have
      efficacy in the treatment of deep vein thrombosis, as well as in the management
      of acute coronary syndromes. However, 1 study reported a significant increase in
      the risk of major bleeding with fondaparinux compared with enoxaparin (2.1% vs
      0.2%, respectively; P = 0.006), and another reported a significant increase in
      the risk of minor bleeding (4.1% vs 2.1%; P = 0.02). CONCLUSIONS: Fondaparinux
      has shown efficacy in the prevention of venous thromboembolism in patients
      undergoing hip or knee replacement surgery. Large-scale clinical trials of its
      potential efficacy in deep vein thrombosis and acute coronary syndromes are
      ongoing. Use of fondaparinux may be associated with an increased bleeding risk,
      and patients should be assessed individually to ensure that the possible benefits
      outweigh the risks. Routine use of fondaparinux as a replacement for low
      molecular-weight heparin is not recommended at this time.

PMID- 12501873
TI  - A prospective, randomized, double-blind multicenter comparison of parenteral
      ertapenem and ceftriaxone for the treatment of hospitalized adults with community
      acquired pneumonia.
AB  - BACKGROUND: Ertapenem is a once-daily parenteral beta-lactam licensed in the
      United States in November 2001 and in Europe in May 2002. OBJECTIVE: This study
      compared the efficacy and safety profiles of ertapenem with those of ceftriaxone
      for the treatment of hospitalized adult patients with serious community-acquired
      pneumonia (CAP) requiring parenteral therapy. METHODS: In this prospective,
      double-blind (with sponsor blinding), multicenter study, adult patients with CAP
      were stratified by Pneumonia Severity Index (< or = 3 or > 3) and age (< or = 65
      or > 65 years) and randomized (2:1) to receive IV or intramuscular (IM) ertapenem
      1 g once daily or IV or IM ceftriaxone 1 g once daily. Investigators could switch
      patients to an oral antimicrobial agent if clinical improvement was shown after
      at least 3 days of parenteral therapy. RESULTS: A total of 364 patients were
      randomized to treatment: 239 to the ertapenem group and 125 to the ceftriaxone
      group. Three patients in the ertapenem group and 2 in the ceftriaxone group did
      not receive study therapy. Of the treated patients, 77.1% (182/236) of patients
      in the ertapenem group and 75.6% (93/123) in the ceftriaxone group were
      clinically evaluable. Among clinically evaluable patients, the mean (SD)
      durations of parenteral and total (parenteral plus optional oral) therapy were
      5.5 (2.6) and 11.5 (2.7) days for ertapenem and 5.6 (2.8) and 11.7 (3.0) days for
      ceftriaxone, respectively. Streptococcus pneumoniae was the most frequently
      isolated pathogen in both treatment groups. Cure rates were 92.2% for clinically
      evaluable patients in the ertapenem group and 93.6% for those in the ceftriaxone
      group (95% CI for the difference, adjusted for stratum, -8.6 to 5.7), fulfilling
      the criteria for statistical equivalence. At completion of parenteral therapy,
      94.7% of patients in the ertapenem group and 95.8% in the ceftriaxone group
      showed clinical improvement. Infused vein complications (ertapenem, 3.4% [8/236];
      ceftriaxone, 7.3% [9/123]) and elevated transaminase levels (ertapenem, 6.3%
      [13/207]; ceftriaxone, 7.1% [8/113]) were the most common adverse events in both
      groups. CONCLUSIONS: In this study of hospitalized adult patients, ertapenem
      therapy, with an oral switch option, was as effective as ceftriaxone with the
      same oral switch option for treatment of CAP requiring initial parenteral
      therapy. The overall safety profiles of the 2 drugs were comparable.

PMID- 12501874
TI  - Risk for respiratory events in a cohort of patients receiving inhaled zanamivir:
      a retrospective study.
AB  - BACKGROUND: Inhaled zanamivir is indicated for treatment of uncomplicated acute
      illness due to influenza A and B viruses in patients aged > or = 12 years who
      have been symptomatic for no more than 2 days. OBJECTIVE: The primary objective
      of this study was to estimate the incidence of adverse respiratory events among
      zanamivir-treated patients under conditions of usual care. METHODS: The Ingenix
      research database includes insurance claims for all dispensations, inpatient and
      outpatient services, and procedures including the associated diagnoses and costs
      for a subset of all enrolled UnitedHealthcare members. We identified all persons
      with a dispensation of zanamivir recorded between October 1, 1999, and April 30,
      2000. We captured medical and pharmaceutical claims data for the 6 months before
      the dispensation to obtain information about comorbidities, overall health
      status, and respiratory events. Medical and hospital record abstraction and
      clinical review served to confirm inpatient/emergency department (ED) events. We
      also examined the records of an approximately 10% random sample of patients
      treated for a potential respiratory event in an outpatient/ physician office
      visit during the 10-day follow-up period. Respiratory events not sufficiently
      severe to result in medical care were not captured in this study. RESULTS: A
      total of 5498 eligible zanamivir dispensations contributed by 5450 patients (2911
      females, 2539 males; mean age, 38.8 years), with 40 confirmed inpatient/ED
      respiratory events, were included in the study. Of these 40 events, 31 were
      pneumonia, bronchitis, or exacerbations of existing chronic respiratory disease;
      none required intubation or ventilation. No events occurred on the dispensation
      date. The overall risk for an inpatient/ ED respiratory event was 0.7 per 100
      episodes (95% CI, 0.5-1.0). Seven events of wheezing or shortness of breath were
      not an obvious extension of the original influenza-like illness or of a
      complicating bronchitis (risk = 0.13 per 100 episodes; 95% CI, 0.06-0.26).
      CONCLUSIONS: No immediate or severe bronchoconstrictive responses occurred among
      5498 zanamivir dispensations. The overall risk for any respiratory event was low,
      and none was sufficiently severe to suggest respiratory failure.

PMID- 12501875
TI  - A comparison of the relative clinical efficacy of a single dose of ketotifen
      fumarate 0.025% ophthalmic solution versus placebo in inhibiting the signs and
      symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen
      challenge model.
AB  - BACKGROUND: Ketotifen fumarate 0.025% ophthalmic solution is an antiallergic
      treatment currently available in the United States. It is indicated for the
      temporary prevention of ocular itching due to allergic conjunctivitis. OBJECTIVE:
      The purpose of this study was to determine the relative efficacy of ketotifen
      when applied topically to the eye, compared with placebo, in the treatment of
      nasal signs and symptoms of allergic rhinoconjunctivitis as induced by the
      conjunctival allergen challenge (CAC) model. METHODS: This was a randomized,
      double-blind, parallel-group, single-center clinical study using the CAC model.
      Patients aged > or = 18 years, able to follow the study instructions, willing to
      avoid disallowed medications, and having a history of rhinoconjunctivitis and a
      positive skin test were eligible. At visit 1, the dose of allergen necessary to
      achieve a qualifying reaction was determined using bilateral ocular instillation
      of allergen to eligible patients. At visit 2, the allergen dose determined at
      visit 1 was confirmed, and all patients attaining a qualifying nasal reaction
      continued in the study. At visit 3, each patient was randomized to receive 1 drop
      of ketotifen bilaterally in the eyes or 1 drop of placebo bilaterally. Fifteen
      minutes after instillation of the study medication, bilateral CAC was performed.
      Patients rated nasal symptoms (sneezing, rhinorrhea and postnasal drip, nasal
      pruritus, palatal pruritus, and nasal congestion) on standardized scales at 10,
      20, and 30 minutes after CAC. RESULTS: Thirty-two patients (16 men, 16 women;
      mean age, 45 years [range, 28-70 years]) were randomized to treatment and
      completed the study. Nineteen patients received ketotifen and 13 received
      placebo. Nasal symptom scores in ketotifen-treated patients were statistically
      and clinically significantly fewer than in those treated with placebo at all time
      points (mean baseline corrected total nasal score: 10 minutes, P = 0.010; 20
      minutes, P = 0.025; 30 minutes, P = 0.006). CONCLUSION: In this study, topical
      ketotifen fumarate 0.025% ophthalmic solution, when dosed ocularly, offered
      protecdon against the nasal signs and symptoms of acute allergic
      rhinoconjunctival reaction as induced by the CAC model.

PMID- 12501876
TI  - Open-label study of the effect of combination quetiapine/lithium therapy on
      lithium pharmacokinetics and tolerability.
AB  - OBJECTIVE: The aim of this study was to assess the effect of oral quetiapine on
      the steady-state pharmacokinetics of lithium. METHODS: This was an open-label
      trial in patients with schizophrenia, schizoaffective disorder, or bipolar
      disorder who had demonstrated tolerability to combination lithium/ antipsychotic
      therapy. Patients received lithium for at least 1 week before screening and
      throughout the 18-day trial. Quetiapine was coadministered in fixed, stepwise,
      increasing doses of 25 to 250 mg TID on days 4 through 11, and maintained at 250
      mg TID on days 12 through 14. Blood samples were drawn to monitor plasma
      concentrations of lithium and quetiapine. Psychiatric assessments included the
      Brief Psychiatric Rating Scale, the Clinical Global Impression severity of
      illness item, and the modified Scale for the Assessment of Negative Symptoms.
      Neurologic function was assessed using the Simpson-Angus Scale and the Abnormal
      Involuntary Movement Scale. Other assessments included clinical laboratory
      testing, electrocardiography, physical examinations, and monitoring for
      spontaneously reported adverse events. RESULTS: Nine men and 1 woman (mean [SE]
      age, 32.8 [1.9] years; mean [SE] body weight, 87.6 [3.3] kg) entered and
      completed the 18-day trial. Eight patients had bipolar disorder, 1 had paranoid
      schizophrenia, and 1 had schizoaffective disorder. Morning trough concentrations
      of lithium in serum (days 2, 6, 8, 10, 12, 14, and 17), as well as quetiapine and
      2 of its metabolites in plasma (days 12, 13, and 14), did not appear to vary
      noticeably. Small increases were observed in the mean values of the area under
      the 12-hour serum lithium concentration-time curve and the maximum and minimum
      observed serum lithium concentrations when quetiapine was added to the lithium
      regimen. However, the increases were not considered clinically relevant by the
      investigators and were not statistically significant. A total of 91 adverse
      events were reported, 67 (73.6%) of which were not attributed to trial treatment.
      The most commonly reported adverse events during coadministration of lithium and
      quetiapine were somnolence (90.0% [9/10]), asthenia (70.0% [7/10]), dry mouth
      (30.0% [3/10]), nausea (30.0% [3/10]), vomiting (30.0% [3/10]), dizziness (30.0%
      [3/10]), tremor (30.0% [3/10]), and insomnia (20.0% [2/10]). There were no
      serious adverse events. CONCLUSIONS: Measures of lithium and quetiapine
      concentrations did not vary significantly during combination therapy.
      Coadministered lithium and quetiapine were well tolerated in the patients
      studied.

PMID- 12501877
TI  - The effect of zanamivir treatment on influenza complications: a retrospective
      cohort study.
AB  - BACKGROUND: Complications of influenza are a major cause of morbidity and
      mortality during the influenza season. Clinical trials of zanamivir have reported
      a reduced incidence of influenza complications among high-risk patients.
      OBJECTIVES: This retrospective study sought to determine whether the use of
      zanamivir lowers the risk of acute influenza complications in a broader
      population, based on an analysis of claims data from a large managed care
      organization. METHODS: Medical and pharmacy health insurance claims data from
      October 1, 1999, through April 30, 2000, were compiled for UnitedHealthcare
      members in 19 states. All patients with a diagnosis of influenza (International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code
      487.xx) associated with a physician visit were identified. From these, all
      patients were selected who had received zanamivir on the same day as the
      diagnosis of influenza. The propensity score matching technique was used to
      identify a comparison group with similar health service utilization and
      comorbidities who received a diagnosis of influenza but no antiviral therapy.
      Follow-up started the day after the influenza diagnosis and continued for 21
      days. RESULTS: From the 43,741 patients originally identified, 2341 were selected
      who received a simultaneous diagnosis of influenza and a prescription for
      zanamivir. The untreated comparator group numbered 2337. Fewer zanamivir patients
      than untreated patients were hospitalized for complications, and the absolute
      risks were low (0.6% and 1.0%, respectively; risk ratio [RR], 0.58; 95% CI, 0.30
      1.12). Zanamivir-treated patients had an excess of outpatient visits (16.9% vs
      14.5%; RR, 1.16; 95% CI, 1.02-1.33) and antibiotic use (16.3% vs 14.8%; RR, 1.10;
      95% CI, 0.97-1.26), although the RRs were modest. CONCLUSIONS: In the setting of
      a large managed care plan, patterns of influenza complications were similar in
      zanamivir-treated and untreated patients with a diagnosis of influenza. The
      results of this study are in contrast to those of published clinical trials
      reporting a reduction in the risk of influenza complications in zanamivir-treated
      patients.

PMID- 12501878
TI  - Cefditoren pivoxil versus cefpodoxime proxetil for community-acquired pneumonia:
      results of a multicenter, prospective, randomized, double-blind study.
AB  - BACKGROUND: According to recently issued treatment guidelines, appropriate
      empiric choices for ambulatory patients with community-acquired pneumonia (CAP)
      are a macrolide, doxycycline (for patients aged > or = 8 years), or an oral beta
      lactam agent with good activity against pneumococci. OBJECTIVE: This study was
      designed to compare cefditoren pivoxil, a new beta-lactam, with cefpodoxime
      proxetil, a beta-lactam with an established role in the treatment of CAP.
      METHODS: This was a multicenter, prospective, randomized, double-blind study
      conducted in the United States and South Africa. Ambulatory patients with a
      diagnosis of CAP were randomized to 14 days of treatment with cefditoren 200 or
      400 mg BID or cefpodoxime 200 mg BID. Assessments of clinical cure and pathogen
      eradication were conducted at 2 visits during treatment, 1 posttreatment visit
      (s48 hours after completion of treatment), and 1 follow-up visit (7-14 days after
      completion of treatment). The development of resistant pathogens was assessed at
      the follow-up visit but not thereafter. The relative cost of treatment was not
      assessed. RESULTS: The study enrolled 851 patients. Comparable clinical cure
      rates were observed among evaluable patients in the 3 treatment groups at both
      the posttreatment and followup visits: at the posttreatment visit, cure rates
      were 90.5% (162/179) for cefditoren 200 mg, 89.7% (148/165) for cefditoren 400
      mg, and 92.2% (153/166) for cefpodoxime 200 mg; at the follow-up visit, they were
      a respective 88.4% (160/181), 87.2% (143/164), and 90.4% (151/167). Of the 171
      strains of Streptococcus pneumoniae isolated before treatment, 22 (12.9%) had
      reduced susceptibility to penicillin, 5 (2.9%) of them penicillin resistant
      (minimum inhibitory concentration > or = 2 microg/mL). At the posttreatment
      visit, the overall eradication rates of pathogens isolated from microbiologically
      evaluable patients were 88.7% (134/151), 89.9% (134/149), and 95.7% (134/140) in
      the respective treatment groups (P = 0.031, cefditoren 200 mg vs cefpodoxime).
      Eradication rates of S pneumoniae were 93.8% (45/48), 95.7% (45/47), and 95.6%
      (43/ 45) in the respective treatment groups; those of Haemophilus influenzae were
      90.2% (46/51), 97.7% (43/44), and 97.4% (37/38). The rates of resolution and/or
      improvement in clinical signs and symptoms were comparable between groups. The
      study drugs were well tolerated, with 1.7%, 2.5%, and 1.4% of patients in the
      respective groups discontinuing study drug prematurely due to a treatment-related
      adverse event, the majority of these associated with the digestive system.
      CONCLUSION: The results of this study suggest that cefditoren may have a role in
      the treatment of CAP in ambulatory patients.

PMID- 12501879
TI  - A comparison of cefditoren pivoxil and amoxicillin/ clavulanate in the treatment
      of community-acquired pneumonia: a multicenter, prospective, randomized,
      investigator-blinded, parallel-group study.
AB  - BACKGROUND: Cefditoren pivoxil is a broad-spectrum cephalosporin that is approved
      for the treatment of pharyngitis, acute exacerbations of chronic bronchitis, and
      skin and skin-structure infections. OBJECTIVE: This study was conducted to
      examine the efficacy and tolerability of cefditoren in the treatment of community
      acquired pneumonia (CAP). Amoxicillin/clavulanate was chosen as a comparator
      because of its established efficacy and general acceptance as a standard of care
      in CAP. METHODS: This multicenter, prospective, randomized, investigator-blinded,
      parallel-group trial compared oral cefditoren 200 and 400 mg BID with oral
      amoxicillin/clavulanate 875/125 mg BID for 14 days in adult outpatients with CAP.
      RESULTS: Eight hundred two patients (404 men, 398 women; mean age, 50 years; age
      range, 12-93 years) with CAP were enrolled. Comparable clinical cure rates were
      observed among evaluable patients in all treatment groups at both the
      posttreatment and follow-up visits: 88.0% (125/142) for cefditoren 200 mg, 89.9%
      (143/159) for cefditoren 400 mg, and 90.3% (130/144) for amoxicillin/clavulanate
      at the posttreatment visit, and 86.5% (128/148), 86.8% (138/159), and 87.8%
      (129/147) for the respective groups at the follow-up visit. Of 82 Streptococcus
      pneumoniae strains isolated before treatment, 22 (26.8%) had reduced
      susceptibility to penicillin, 12 (14.6%) of them penicillin resistant. Overall
      eradication rates at the posttreatment visit for pathogens isolated from
      microbiologically evaluable patients were 84.0%, 88.6%, and 82.6% for cefditoren
      200 mg, cefditoren 400 mg, and amoxicillin/clavulanate, respectively. In the
      respective treatment groups, 80.6%, 88.6%, and 88.0% of Haemophilus influenzae
      strains and 95.0%, 96.2%, and 89.5% of S pneumoniae strains were eradicated. The
      rates of resolution of or improvement in clinical signs and symptoms were
      comparable between treatment groups. The treatment regimens were well tolerated,
      with 4.9%, 3.0%, and 5.2% of patients in the respective treatment groups
      requiring discontinuation of study drug due to an adverse event. CONCLUSIONS: In
      this study in adult outpatients with CAP, both doses of cefditoren demonstrated
      equivalence to amoxicillin/clavulanate based on rates of clinical and
      microbiologic cure. All 3 regimens were effective in resolving or improving the
      clinical signs and symptoms of CAP. Both cefditoren and amoxicillin/ clavulanate
      were well tolerated.

PMID- 12501880
TI  - Patient preference for once-weekly alendronate 70 mg versus once-daily
      alendronate 10 mg: a multicenter, randomized, open-label, crossover study.
AB  - BACKGROUND: Alendronate, an oral bisphosphonate, is available for the treatment
      of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation.
      OBJECTIVES: This study aimed to determine patient preference for once-weekly
      versus once-daily dosing with alendronate, and to determine which treatment
      regimen the patients believed was more convenient and would be easier to comply
      with for a long period. METHODS: This was a multicenter, randomized, open-label,
      preference study in which postmenopausal women with osteoporosis were enrolled to
      receive 9 weeks of treatment in crossover fashion (4 weeks with each study
      regimen separated by a 1-week washout period). The study regimens included once
      weekly alendronate 70 mg and once-daily alendronate 10 mg. The primary and
      secondary end points were assessed with a questionnaire completed by the patient.
      Adverse events (AEs) were recorded to assess patient tolerability of the study
      medications. RESULTS: A total of 324 patients met the eligibility requirements;
      288 were randomized to treatment, 287 (mean age, 64.8 years) received treatment,
      272 completed the questionnaire, and 266 completed the study. Of the patients who
      completed the questionnaire, 235 patients preferred the 70-mg once-weekly dosing
      regimen compared with the 10-mg once-daily regimen (86.4% vs 9.2%; P < 0.001).
      Most patients also believed that once-weekly dosing was more convenient than once
      daily dosing (89.0% vs 7.7%; P < 0.001) and would allow them to achieve better
      long-term compliance (87.5% vs 8.5%; P < 0.001). Clinical AEs were reported in
      30.7% of patients treated with once-weekly alendronate and 30% of patients
      treated with once-daily alendronate, with no significant differences between
      treatments. CONCLUSION: When once-weekly alendronate 70 mg was compared with once
      daily alendronate 10 mg in this study, 70-mg once-weekly alendronate was the
      preferred dosing regimen.

PMID- 12501881
TI  - The pharmacokinetics of sumatriptan when administered with norethindrone 1
      mg/ethinyl estradiol 0.035 mg in healthy volunteers.
AB  - BACKGROUND: Because the majority of migraineurs are young women in their peak
      reproductive years, it is important to understand the possible effects on the
      pharmacokinetics of both medications when sumatriptan is coadministered with an
      oral contraceptive (OC). OBJECTIVES: The primary objective of this study was to
      assess the effect of multiple dosing of the OC norethindrone 1 mg/ethinyl
      estradiol 0.035 mg (NE/EE) on the single-dose pharmacokinetics of sumatriptan in
      healthy volunteers. Secondary objectives were to determine the effect of a single
      dose of sumatriptan on the multiple-dose pharmacokinetics of NE and EE, and to
      assess the safety and tolerability of the combination. METHODS: This was an open
      label, 1-sequence, crossover study in healthy women who had been receiving NE/EE
      for at least 3 months. Subjects received 1 cycle of NE/EE, consisting of 21 days
      of OC and 7 days of placebo. They also received a single dose of sumatriptan 50
      mg on the last day of the OC or placebo regimen. Blood samples for the
      determination of plasma sumatriptan concentrations were collected on days 21 and
      28, and blood samples for the determination of plasma NE and EE concentrations
      were collected on days 20 and 21. Treatments were compared by analysis of
      variance. Equivalence between treatments was to be concluded if the 90% Cl for
      the ratio of reference to test means for log(e)-transformed parameters (area
      under the plasma concentration-time curve [AUCI and maximum measured plasma
      concentration [C(max)]) for each analyte fell within the interval 0.80 to 1.25.
      RESULTS: Twenty-six women (mean age, 29.8 years; age range, 18-44 years; weight
      range, 52-82 kg) participated in the study. The 90% CI for the ratio of reference
      to test means for the AUC extrapolated to infinity (AUC(infinity)) of sumatriptan
      was 1.11 to 1.22, and the 90% CIs for the AUC over the dosing interval at steady
      state (AUC(tau)) of NE and EE were 0.96 to 1.00 and 0.91 to 0.97, respectively.
      The 90% CIs for the ratio of reference to test means for the C(max) of
      sumatriptan, NE, and EE were a respective 1.05 to 1.30, 0.76 to 0.88, and 0.88 to
      1.04. Study treatments were well tolerated. Adverse events were mild or moderate,
      and there were no clinically significant changes in vital signs or laboratory
      values. CONCLUSIONS: The extent of absorption (AUC) of sumatriptan, NE, and EE
      was similar after oral administration of sumatriptan and NE/EE, both alone and in
      combination. Thus, in the opinion of the study investigators, there were no
      clinically relevant changes in the AUC of any of the medications when sumatriptan
      and NE/EE were administered concomitantly compared with administration alone. The
      results of this study suggest that dose adjustment is not necessary when
      sumatriptan is administered concomitantly with NE/EE in healthy premenopausal
      women.

PMID- 12501882
TI  - A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg
      for suppression of testosterone in patients with prostate cancer.
AB  - OBJECTIVE: The safety, efficacy, and pharmacokinetics of monthly subcutaneous
      injections of a new leuprolide acetate (LA) depot formulation were investigated
      in patients with advanced prostate cancer. METHODS: The 2-part, 6-month (168
      day), open-label, multicenter study enrolled male patients diagnosed with
      adenocarcinoma of the prostate (Jewett stage C or D). LA-2500 7.5-mg (a new
      subcutaneous depot formulation containing 7.5 mg of LA) injections were
      administered at monthly (28-day) intervals. The primary efficacy parameter was
      total serum testosterone level. A breakthrough response was defined as a single
      testosterone measurement > 50 ng/dL after achieving castration testosterone
      levels. Testosterone was isolated from sera by alumina column chromatography and
      measured by radioimmunoassay (RIA). LA was purified by solid-phase extraction and
      high-performance liquid chromatography and was then quantitated by RIA. RESULTS:
      One hundred seventeen of the 120 enrolled patients completed the 6-month study.
      Three patients withdrew for reasons not related to treatment. LA had a mean (SD)
      maximal concentration of 26.3 (12.6) ng/mL at 4.66 (1.44) hours and was detected
      for a mean of 37 days (range, 28-49 days). By day 28, 94.1% (112/119) of the
      patients achieved medical castration (serum testosterone < or = 50 ng/dL). By day
      42, 100.0% (118/118) of the patients remaining in the study had serum
      testosterone levels < or = 50 ng/dL and 97.5% (115/118) had levels < or = 20
      ng/dL. At study completion, the mean (SD) serum testosterone level was 6.12 (4.3)
      ng/dL (range, 3.0-27.0 ng/dL). No breakthrough or acute-on-chronic responses were
      reported throughout the study. From baseline to month 6, mean (SD) luteinizing
      hormone level decreased from 8.0 (7.3) mIU/mL to 0.09(0.1) mIU/mL, and mean (SD)
      prostate-specific antigen level decreased from 32.9 (86.3) ng/mL to 3.2 (12.0)
      ng/mL. Treatment-related adverse events were reported by 74.2% (89/120) of
      patients, the most common being hot flashes (56.7%). CONCLUSION: This 6-month,
      open-label, noncontrolled study showed LA-2500 7.5-mg depot was well tolerated
      and maintained testosterone suppression (< or = 50 ng/dL) in the patients
      completing the study without any testosterone breakthrough responses.

PMID- 12501883
TI  - Oral gemifloxacin versus sequential therapy with intravenous ceftriaxone/oral
      cefuroxime with or without a macrolide in the treatment of patients hospitalized
      with community-acquired pneumonia: a randomized, open-label, multicenter study of
      clinical efficacy and tolerability.
AB  - OBJECTIVE: This study aimed to compare the efficacy and safety of oral
      gemifloxacin, an enhanced-affinity quinolone, with sequential therapy with IV
      ceftriaxone followed by oral cefuroxime (with or without a macrolide) in patients
      hospitalized for community-acquired pneumonia (CAP). METHODS: A randomized, open
      label, multicenter study comprised adults hospitalized with a clinical and
      radiologic diagnosis of CAP. Patients were randomized 1:1 to receive either (1)
      oral gemifloxacin 320 mg once daily (7-14 days); or (2) IV ceftriaxone 2 g once
      daily (1-7 days) followed by oral cefuroxime 500 mg twice daily (1-13 days) for a
      total of < or = 14 days. Patients receiving ceftriaxone/cefuroxime were allowed
      concomitant macrolide treatment. RESULTS: A total of 345 patients were
      randomized, of whom 341 received at least 1 dose of study medication
      (gemifloxacin, 169/172; ceftriaxone/cefuroxime, 172/173). Clinical success rates
      in the clinically evaluable (CE) population at follow-up (day 21-28 post
      therapy), the primary end point, were 92.2% (107/116) for gemifloxacin and 93.4%
      (113/121) for ceftriaxone/cefuroxime (treatment difference, -1.15; 95% CI, -7.73
      to 5.43). In patients in Fine risk classes IV and V, the clinical success rate
      was 87.0% (20/23) for gemifloxacin versus 83.3% (20/24) for
      ceftriaxone/cefuroxime. No difference in clinical response at follow-up was noted
      based on macrolide use. Bacteriologic success rates at follow-up in the
      bacteriologically evaluable (BE) population were 90.6% (58/64) for gemifloxacin
      and 87.3% (55/63) for ceftriaxone/cefuroxime (treatment difference 3.32; 95% CI, 
      7.57 to 14.21). The clinical success rate in bacteremic patients at follow-up (BE
      population) was 100.0%. Both treatments were generally well tolerated. The
      frequency and types of adverse events were similar between the 2 groups. The most
      common treatment-related adverse events with gemifloxacin were diarrhea, liver
      function adverse events, and rash; with ceftriaxone/cefuroxime, they were
      diarrhea, elevated hepatic-enzyme activity, and moniliasis. CONCLUSION: The
      clinical efficacy and tolerability of oral gemifloxacin 320 mg once daily were
      similar to those of IV ceftriaxone followed by oral cefuroxime (with or without a
      macrolide) in the treatment of adult patients hospitalized with moderate to
      severe CAP. Both treatments were effective in bacteremic patients and those at
      increased risk of mortality.

PMID- 12501884
TI  - A retrospective analysis of the revocation of prior authorization restrictions
      and the use of antidepressant medications for treating major depressive disorder.
AB  - BACKGROUND: The California Medicaid (Medi-Cal) program removed prior
      authorization restrictions for 2 selective serotonin reuptake inhibitors (SSRIs),
      fluoxetine and paroxetine, in May 1996. OBJECTIVE: This article documents how
      open access affected patient compliance and the likelihood of switching
      antidepressant therapies. METHODS: All Medi-Cal patients with a paid claim who
      had a diagnosis of major depressive disorder (MDD) from September 1994 through
      January 1999 were eligible. The impact of open access on patient compliance and
      drug switching was investigated using logistic regression models. Completed
      therapy was defined as 180 days of uninterrupted drug therapy at a minimum
      therapeutic dose. RESULTS: A total of 6409 patient treatment episodes were
      identified, of which 80% involved the use of an antidepressant. The aggregate
      rate of drug therapy completion dropped from 23.2% before the change in formulary
      policy to 20.5% in the open-access period. There was no corresponding change in
      the likelihood of switching therapies. For fluoxetine-treated patients, the odds
      ratio for completing therapy relative to tricyclic antidepressant-treated
      patients dropped from 3.916 to 1.706 in the open-access period. Corresponding
      results for paroxetine-treated patients were 1.591 and 0.726, respectively. The
      reduction in the likelihood of completed therapy without a corresponding increase
      in switching is consistent with earlier results. Open access resulted in an
      influx of patients who were not previously treated with an antidepressant or
      reported by their physician as having an MDD. Physicians may have expanded the
      use of the open-access SSRIs to treat less severely ill patients. However, paid
      claims data do not provide sufficient information to accurately measure severity
      of illness. CONCLUSIONS: It is unclear whether patients benefited clinically from
      the expansion of the Medi-Cal formulary. The significant changes in the
      characteristics of the patient population in response to open access (access
      effect) complicate attempts to measure the impact of open access on treatment
      patterns. Future analysis of the impact of open access on the cost of treating an
      episode of depression will also have to address this issue.

PMID- 12501885
TI  - Results of an economic model to assess the cost-effectiveness of enoxaparin, a
      low-molecular-weight heparin, versus warfarin for the prophylaxis of deep vein
      thrombosis and associated long-term complications in total hip replacement
      surgery in the United States.
AB  - BACKGROUND: Premature death due to pulmonary embolism is a short-term
      complication of deep vein thrombosis (DVT). The long-term clinical course after
      DVT can be further complicated by excess mortality, recurrent venous
      thromboembolism (VTE), and the post-thrombotic syndrome (PTS), which may produce
      sizable long-term economic burdens. OBJECTIVE: The goal of this study was to
      determine the cost-effectiveness of the low-molecular-weight heparin (LMWH)
      enoxaparin versus warfarin for the universal prophylaxis of DVT and associated
      long-term complications in US patients undergoing total hip replacement surgery
      (THRS). METHODS: A model was constructed to assess the long-term cost
      effectiveness of the 2 treatments. Patients undergoing THRS were exposed to a
      short-term risk of developing a DVT. Patients surviving a DVT were exposed to
      increased risk of long-term complications of DVT, including PTS, recurrent VTE,
      and increased mortality. Published literature, augmented by expert opinion,
      served as input for the model's resource use and costs for DVT prophylaxis,
      clinical diagnosis, and treatment of DVT, VTE, and PTS. RESULTS: When the
      analysis included only the short-term consequences of DVT, therapy with
      enoxaparin resulted in a net cost of $133 per patient and a net increase of 0.04
      quality-adjusted life-years (QALYs) per patient. Thromboprophylaxis with
      enoxaparin versus warfarin resulted in $3733 per QALY saved. In contrast, when
      the long-term consequences of DVT were included, enoxaparin resulted in net
      lifetime savings of $89 per patient and net QALY benefits of 0.16 per patient.
      CONCLUSIONS: To the best of our knowledge, this is the first US economic analysis
      comparing DVT prophylaxis with the LMWH enoxaparin versus warfarin that included
      the long-term complications of DVT. Our model suggests that use of enoxaparin in
      patients undergoing THRS reduces the economic burden associated with these long
      term complications.

PMID- 12501886
TI  - Molecular genetic control of caspases and JNK-mediated neural cell death.
AB  - Programmed cell death, or apoptosis, plays crucial roles in both development and
      tissue homeostasis. Apoptosis is widely observed in the nervous system during
      development. However, the molecular mechanisms underlying why only certain cells
      are selected to die and the execution of neural cell death itself are largely
      unknown. Recent genetic studies in mice and Drosophila revealed crucial roles for
      JNK (c-jun N-terminal kinase) activation in neural cell death. The JNK-mediated
      initiation of apoptotic mechanisms appears to be an excellent strategy for the
      fine-tuning of morphogenesis as well as cell selection in nervous tissue.

PMID- 12501887
TI  - Apoptosis induced by generated OH radicals inside cells after irradiation.
AB  - OH radicals play a major role in radiation-induced DNA and cell membrane damage.
      These types of damage can also induce death by apoptosis through activation of a
      pro-apoptosis pathway. We attempted to detect OH radicals inside human
      promyelocytic leukemia (HL60) cells and estimate the relationship between
      radiation-induced apoptosis and OH radicals generated inside the cells. Electron
      spin resonance spectroscopy showed that OH radicals were generated by X-rays
      within irradiated cell pellets and the relative signal intensities of OH radicals
      increased with the radiation dose. Agarose gel electrophoresis revealed that the
      death of HL60 cells by apoptosis was accompanied by internucleosomal DNA
      fragmentation at 2 h after irradiation with 10-30 Gy. On ultrastructure
      evaluation by transmission electron microscopy, certain irradiated HL60 cells
      demonstrated condensed chromatin forms at the nuclear membrane and nuclear
      fragmentation. The frequency of apoptotic cells with condensation and
      fragmentation of nuclear chromatin increased with radiation dose in semithin
      sections. The increase of quantitative DNA fragmentation and percentage of non
      living cells also correlated with radiation dose. These results suggest that OH
      radicals are generated inside cells before apoptosis occurs. The amount of OH
      radicals generated correlates with apoptotic cell death.

PMID- 12501888
TI  - Fibroblasts and antigen-presenting cells in the renal interstitium of
      streptozotocin-induced diabetic rats on a high cholesterol diet.
AB  - The cortical peritubular interstitium of the normal kidney contains both
      fibroblasts and antigen-presenting dendritic cells. Characteristics of these
      interstitial cells were analyzed in an overnutrition model by electron microscopy
      after the cold-dehydration technique and immunohistochemistry for antigen
      presenting cells. In control rats, fibroblasts and dendritic cells were clearly
      identified by electron microscopy on the basis of their distinct ultrastructures.
      Fibroblasts possessed slender cell processes, and contained an abundance of actin
      filament bundles occasionally anchoring to surrounding structures, whereas
      dendritic cells possessed irregularly-shaped cell processes with a clear
      cytoplasm and a paucity of actin filament bundles. In the experimental kidney
      from diabetic rats given a high cholesterol diet, the peritubular interstitium
      contained fibroblasts and vacuolated cells, and the extracellular matrices such
      as collagen bundles were distinctly increased compared with the control rat
      kidney. Immunohistochemical staining with OX6 and ED1 revealed that the
      peritubular interstitium in the control rat kidney contained dendritic cells,
      while that in the experimental rats was occupied by macrophages. The present
      study provides the first evidence indicating that overnutrition may dramatically
      affect the immune cells in nonlymphoid tissue.

PMID- 12501889
TI  - Anatomical and neuropeptidergic properties of the duodenal neurons projecting to
      the gallbladder in the golden hamster.
AB  - This study investigated the anatomical and neuropeptidergic properties of the
      duodenal neurons projecting to the gallbladder in the golden hamster. Fast blue
      (FB) was injected into the subserosa of the gallbladder in order to identify by
      retrograde tracing the duodenal neurons that project to the gallbladder.
      Subsequently, immunofluorescence microscopy was employed to see whether these
      duodenal neurons contained putative peptidergic neurotransmitters such as
      calcitonin gene-related peptide (CGRP), galanin (GAL) and vasoactive intestinal
      polypeptide (VIP). The FB-labeled cells were only found in the duodenal region
      adjacent to the major duodenal papilla where the biliary duct opens. On the other
      hand, there was no difference within this duodenal region in the numbers of FB
      labeled cells between the mesenteric and antimesenteric portions, suggesting that
      these two portions of the duodenum equally contribute neuronal projections to the
      gallbladder. Double-immunofluorescence microscopy clearly demonstrated that a
      small population of FB-positive duodenal neurons contained putative
      neurotransmitters CGRP, GAL and VIP. Our data suggest that duodenal neurons
      around the major duodenal papilla in the golden hamster project to the
      gallbladder and exert their influence on the gallbladder via neuropeptides such
      as CGRP, GAL and VIP.

PMID- 12501890
TI  - The organization of the communication routes between the epithelium and lamina
      propria mucosae in the human esophagus.
AB  - Morphological studies examined communication routes between the epithelium and
      lamina propria mucosae in the human esophagus, using a series of techniques
      including silver staining, immunohistochemistry, transmission electron
      microscopy, and scanning electron microscopy (SEM). For SEM, tissue blocks were
      treated with either osmium/ultrasonication or NaOH. Observations showed the
      esophageal papillae to be arranged regularly in a mostly longitudinal row. The
      reticular fibers, consisting of fibrils approximately 40 nm in diameter, were
      situated just beneath the epithelial basal lamina. They showed a positive
      reaction with a type III collagen antibody, and formed a continuous sheet 2-3
      microm thick with dense networks. This sheet as well as the epithelial basal
      lamina had numerous foramina of diameters of 3-5 microm. Immune cells such as
      lymphocytes and Langerhans cells were situated around these foramina. The
      foramina were situated both around papillae and the duct orifice of the
      esophageal gland. In addition, lymphoid follicles surrounded the duct of the
      esophageal gland. The structural characteristics around the duct appear to be
      those of duct-associated lymphoid tissue (DALT). Thus, these foramina in the
      epithelial basal lamina and reticular fiber sheet may represent important
      communication routes between the epithelium and lamina propria mucosae. In
      addition, they may play an important role in the mucosal immune response in the
      human esophagus.

PMID- 12501891
TI  - Ca-binding domains in the odontoblast layer of rat molars and incisors under
      normal and pathological conditions.
AB  - We recently reported the presence of high concentrations of a Ca-binding matrix
      in the circumpulpal dentin of rat incisors which had been prevented from
      mineralization by a systemic administration of 1-hydroxyethylidene-1,1
      bisphosphonate (HEBP), a type of bisphosphonates, thus suggesting the role of the
      putative Ca-binding matrix in the appositional mineralization of circumpulpal
      dentin (TAKANO et al., 1998, 2000; OHMA et al., 2000). In this study, we examined
      the distribution of Ca-binding domains in the pulp tissue of normal rat teeth and
      its changes under the influence of HEBP, in order to identify and clarify the
      role of the Ca-binding matrix in the physiological process of dentin
      mineralization. Observation of the normal rat tooth pulp showed occasional, tiny
      extracellular deposits of Ca-enriched material in the odontoblast layer,
      associated primarily with pericapillary regions. Such deposits were
      immunopositive for dentin sialoprotein (DSP), displayed high levels of X-ray
      peaks for calcium and phosphorus, and showed a drastic increase in amount by
      daily injections of HEBP. A brief vascular perfusion of high Ca-containing
      solution in normal animals caused the extensive deposition of Ca-P complexes
      along the basolateral membranes of odontoblasts but not in the other regions of
      the pulp tissue. These data suggest the existence of DSP-enriched extracellular
      Ca-binding domains in the odontoblast layer and also indicate a novel Ca-binding
      property of the basolateral membranes of odontoblasts. Since DSP is primarily
      synthesized as dentin sialophosphoprotein (DSPP) and later cleaved into dentin
      phosphophoryn (DPP) and DSP in odontoblasts, and since DSP has no notable
      affinity for Ca, the sites of DSP-immunopositive Ca-P deposits in the odontoblast
      layer may also contain DPP, a highly phosphorylated acidic protein having a
      strong binding property for calcium. Characteristic Ca-binding properties seen in
      the odontoblast layer appear to be related to the regulation of the appositional
      mineralization of circumpulpal dentin.

PMID- 12501892
TI  - Three-dimensional cytoarchitecture of angiogenic blood vessels in a gelatin sheet
      implanted in the rat skeletal muscular layers.
AB  - To demonstrate the structure of angiogenic blood vessels three-dimensionally, a
      gelatin sponge sheet immersed in a vascular endothelial growth factor (VEGF)
      solution was implanted in the rat dorsal muscular layer, and examined by light
      microscopy and scanning electron microscopy (SEM) 5 days to 2 weeks after
      implantation. Light microscopy of anti-collagen IV antibody immunostained
      specimens enabled a determination of the basement membrane tube of newly formed
      blood vessels in the implanted sponge sheet. The tubes were 5-40 microm in
      diameter, and sometimes tapered to a slender cord within the vascular network.
      The SEM study of 30% KOH treated tissues revealed two types of tapering ends of
      newly formed blood vessels. One consisted of endothelial cells with
      microprojections, and lacked any investment of pericytes over the length of 5-20
      microm. The other type was a tapering tip of the endothelial tube covered with
      pericytic processes. The presence of long processes of pericytes extending beyond
      the tip of the endothelial tube and connecting to the adjacent vessel wall
      indicates that this type was produced by endothelial tube regression. Thus, the
      present study supports the ideas that endothelial tube formation is followed by
      pericyte coverage at the sprouting tip, and that endothelial tube regression
      precedes pericyte detachment at the regressing site.

PMID- 12501893
TI  - Immunohistochemical localization of napsin and its potential role in protein
      catabolism in renal proximal tubules.
AB  - In a previous in situ hybridization study, we demonstrated the mRNA expression of
      napsin, an aspartic protease of the pepsin family, in the kidney, lung, and
      lymphoid organs of mice. However, findings on the cellular localization of napsin
      at the protein level are controversial, and no information on the subcellular
      localization is available. The present immunohistochemical study revealed the
      cellular and subcellular localization of napsin in mice and rats, and also
      analyzed the influences of chemical-induced proteinuria on the renal expression
      of this enzyme in rats. Immunohistochemistry using a polyclonal antibody against
      mouse napsin showed that napsin immunoreactivity was noticeable in lysosomes of
      renal proximal tubule cells and in lamellar bodies of pulmonary type II alveolar
      cells. In the lung, immunoreactivity was also found in lysosomes of alveolar
      macrophages and on the surface of type I alveolar cells; the immunoreactivities
      in these cells may be due to the uptake and adhesion of napsin secreted from type
      II alveolar cells, since they did not express napsin mRNA. Conversely,
      immunoreactivity for napsin was undetectable in B lymphocytes with intense mRNA
      expression. In puromycin- or doxorubicin-induced proteinuria, napsin mRNA
      expression was markedly elevated in renal proximal tubules, showing
      characteristic distribution patterns. Immunostaining of kidneys with proteinuria
      showed intense immunoreactivity for napsin in congested and enlarged lysosomes,
      called protein absorption droplets. These results indicate that napsin functions
      as a lysosomal protease and is involved in protein catabolism in renal proximal
      tubules.

PMID- 12501894
TI  - Prenatal diagnosis of alpha-thalassemia-1 (SEA type) by chorionic villus
      sampling.
AB  - OBJECTIVE: To describe the experience of prenatal diagnosis for Hb Bart's
      disease, by chorionic villus sampling (CVS) with DNA analysis. DESIGN:
      Descriptive study SETTINGS: Department of Obstetrics and Gynecology, Faculty of
      Medicine, Chiang Mai University. SUBJECTS: Sixteen high risk pregnancies at risk
      of Hb Bart's disease who were eligible for CVS criteria between 1 January, 1999
      and May 31, 2000. MATERIAL AND METHOD: Fetal villi were obtained by either
      transcervical (TC) or transabdominal (TA) CVS route to extract DNA and detect for
      alpha-thal-1 gene deletion (SEA type) with modified Chang's method. The CVS
      results were confirmed by either serial ultrasound or cordocentesis or diagnosis
      after pregnancy termination. MAIN OUTCOME MEASURES: The efficacy, safety and
      pregnancy outcomes. RESULTS: CVS was successfully done in all of 16 cases (5 with
      TC and 11 with TA), The mean gestational age was 13.25 +/- 2.9 weeks. The
      procedure time for TA was shorter than that of TC (4.64 +/- 5.4 vs 10.4 +/- 11.3
      min). The CVS result showed as follows: 3 normal fetuses, 7 alpha-thal-1
      carriers, 4 fetal Hb Bart's, 1 misdiagnosis and 1 failure to diagnosis due to
      technical error. The sensitivity and specificity were 100 per cent (4/4) and
      90.91 per cent (10/11), respectively. One case of Hb Bart's misdiagnosis and one
      failure case were later confirmed for alpha-thal-1 trait and alpha-thal-1/ Hb E
      trait by cordocentesis, respectively. The pregnancy outcomes included 11
      livebirths, 4 terminated cases and 1 fetal loss of continuing pregnancies. No
      serious complications occurred. CONCLUSION: This preliminary experience suggests
      that CVS is an effective method for early prenatal diagnosis of fetal Hb Bart's.

PMID- 12501895
TI  - Effectiveness of ranitidine bismuth citrate based triple therapy for treating
      Helicobacter pylori.
AB  - OBJECTIVE: To determine the efficacy, safety and tolerance of a one week regimen
      of RBC, clarithromycin, and amoxicillin for H. pylori eradication in Thai
      patients. MATERIAL AND METHOD: Patients who were undergoing endoscopy for
      dyspeptic symptoms. On the day of endoscopy, three biopsies were taken for H.
      pylori diagnosis. The patients who had the presence of H. pylori infection by
      positive from rapid urease test or histologic examination were invited to take
      part in an open, prospective study. Patients received a combination of RBC 400
      mg, clarithromycin 500 mg, and amoxicillin 1 g twice daily for 7 days. Repeated
      endoscopy was performed to evaluate H. pylori eradication at least 1 month after
      the end of treatment. Clinical symptoms, side effects and compliance were
      assessed by interview during the study and at follow-up. RESULTS: Thirty nine
      patients with H. pylori infection were included. Male and female rates was 27:12
      with a mean age of 42.8 +/- 11.4 years (range 21-68). There was a 89.74 per cent
      eradication rate by intent-to-treat and 94.59 per cent by per-protocol analysis.
      There were no serious adverse events during the study. Two patients (5.13%)
      stopped the medication because of side effects. Two patients had failure to
      eradication after complete treatment. Subjective improvement of the clinical
      symptoms was found in 92.3 per cent. CONCLUSION: One week's regimen of RBC,
      clarithromycin, and amoxicillin triple therapy resulted in a relatively high
      efficacy, safety and tolerance for H. pylori eradication in Thai patients.

PMID- 12501896
TI  - Extracranial internal carotid stenting in Phramongkutklao Hospital.
AB  - BACKGROUND: Carotid artery occlusive disease is estimated to be the primary cause
      in 20-30 per cent of all strokes. This report was to demonstrate the safety and
      efficacy of the treatment of extracranial stenosis by carotid artery stenting.
      METHOD: From June 1995 to December 2001, there were 13 patients with internal
      carotid stenosis > or = 60 per cent who were eligible for carotid stenting.
      RESULTS: Twelve patients were male. The mean age was 68 years old. Fifty-four per
      cent had neurological symptoms. The percentage of pre stenting stenosis was 86 +/
      8 and the percentage of post stenting stenosis was 18 +/- 15. There were 3
      patients who had complications after the procedure (minor stroke = 2, severe
      bradycardia = 1). One patient died. There were no new or recurrent neurological
      events during the 6 to 84 month-follow-up. CONCLUSIONS: Carotid stent
      implantation may be an alternate treatment for extracranial carotid stenosis.

PMID- 12501897
TI  - Prevalence of epilepsy in rural Thailand: a population-based study.
AB  - BACKGROUND: A study of the community-based burden of illness based upon
      prevalence is needed to plan intervention strategy. PURPOSE: To determine the
      prevalence of epilepsy in a rural population in Thailand. METHOD: From January to
      June, 2000, all of the people in Talardkav sub-district were invited to be
      interviewed and examined by a neurologist who visited their village. RESULTS: Of
      the 2,069 people in 553 households who gave information (72.2% of the total
      households), 43 had a history of seizure and of the 43, 15 were epileptics. The
      prevalence of epilepsy was estimated at 7.2 per 1,000 population. The highest two
      peaks were in the age groups of 5-9 and 25-34 years (17.0, 17.4/1,000,
      respectively). CONCLUSION: The prevalence of epilepsy in rural Thailand is low,
      although probably underestimated, but it is the best to date for rural Thailand.

PMID- 12501898
TI  - Demographic characteristics of women with self use of misoprostol for pregnancy
      interruption attending Maharaj Nakorn Chiang Mai Hospital.
AB  - OBJECTIVE: To ascess the demographic characteristics of pregnant women and their
      partners including details of self use of misoprostol for pregnancy interruption.
      STUDY DESIGN: Prospective descriptive study. SETTING: Department of Obstetrics
      and Gynecology, Maharaj Nakorn Chiang Mai Hospital. SUBJECTS: 103 pregnant women
      with self use of misoprostol for pregnancy interruption from June 1999 to June
      2001. METHOD: All subjects were interviewed use the same set of questionnaires.
      RESULTS: The mean age of the women and their partners were 20.81 +/- 4.10 and
      22.46 +/- 5.05 years old respectively. The mean gestational age was 13.85 +/-
      5.37 weeks. The most common reason for pregnancy interruption was that they
      wanted to continue studying. The number of misoprostol tablets used ranged from 1
      11 and 87.4 per cent of the women applied this drug via the vaginal route. The
      main source of drug purchasing was from friends, while the mean total cost was
      663.16 +/- 711.32 Baht. No major side effect was detected in the present study.
      CONCLUSION: Misoprostol, the agent primarily used for gastric and duodenal ulcer
      prevention, is now used by pregnant women to interrupt their pregnancies. The
      present study is only the evidence reflecting the tip of the iceberg in this
      society, changing in sexual behavior, change in abortion techniques, and
      knowledge on contraception. Though major complications were not found in this
      study, misoprostol should not be considered safe, because several patients have
      encountered bleeding or incomplete abortion and required hospital stay.

PMID- 12501899
TI  - Increasing trend of illicit drug abuse in Thai parturient at Siriraj Hospital.
AB  - OBJECTIVE: To report the magnitude of the problem and to evaluate the outcome of
      maternal illicit drug use in Thai parturients. DESIGN: Retrospective case-control
      study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine
      Siriraj Hospital, Mahidol University. SUBJECT: The subjects were 44,640
      parturients who had deliveries at Siriraj Hospital from January 1998 to December
      2001 and were divided into two groups. The study group consisted of 66
      parturients with a history of illicit drug use and the control group consisted of
      44,574 parturients without a history of illicit drug use. INTERVENTION: Medical
      records of 66 parturients with a history of illicit drug use were reviewed.
      Obstetric statistics of the department were retrieved from the computerized
      database in the Division of Obstetric and Gynecologic Registry. The data were
      analyzed using descriptive statistics. MAIN OUTCOME MEASURE: Characteristics of
      parturients, pregnancy outcome, type and incidence of illicit drug. RESULTS:
      Within the study period, 66 cases of maternal illicit drug use were identifiable
      during the intrapartum period; 65 cases used amphetamine or derivatives and 1
      case used an opioid derivative. The number had risen from 1 case in 1998 to 58
      cases in 2001. Mean age of the patients was 23.30 +/- 6.04 years. Compared to the
      control group which included 44,574 parturients, the patients had a lower
      incidence of antenatal care (ANC rate = 21.21% vs 94.35%; RR = 0.23, 95% CI =
      0.14-0.26), a higher incidence of HIV infection (10% vs 2%; RR = 6.09, 95% CI =
      2.83-13.12), a higher incidence of birth before arrival (BBA rate = 9.09% vs
      1.06%; RR = 8.59, 95% CI = 3.98-18.51), and a lower cesarean section rate (10.60%
      vs 26.36%; RR = 0.40, 95% CI = 0.20-0.81). There were no serious intrapartum,
      immediate postpartum and neonatal complication. Fetal outcome included a higher
      incidence of low birth weight infants (22.73% vs 10.23%; RR = 2.22, 95% CI = 1.42
      3.46) and a smaller head circumference than the normal range of Thai fetal
      biometry (31.85 +/- 1.47 cm). CONCLUSION: There is an increasing trend of illicit
      drug use in Thai parturients. Although the present case series of drug abuse in
      Thai parturients cannot give the whole picture of maternal drug abuse in the Thai
      population, the dramatic increase in the identifiable cases during the past 4
      years is very alarming. Currently, the outcome of pregnancy in case detected
      during intrapartum is not much different from that in the general population.
      However, there are potential risks for the patients and their babies. All medical
      staffs should be aware of this condition. Careful clinical data gathering and
      laboratory testing are suggested for prevention of complications and the
      potential hazards of this problem.

PMID- 12501900
TI  - Entomophthoromycosis in Maharaj Nakorn Chiang Mai Hospital.
AB  - OBJECTIVE: To review documented entomophthoromycosis patients at Maharaj Nakorn
      Chiang Mai Hospital from 1985 to 2001. MATERIAL AND METHOD: A retrospective
      review was performed at Maharaj Nakorn Chiang Mai Hospital from 1985 to 2001.
      Eight cases of entomophthoromycosis were found between 1988 and 1993, with five
      patients diagnosed as subcutaneous zygomycosis, I GI entomophthoromycosis and 2
      rhinofacial zygomycosis. RESULTS: The subcutaneous zygomycosis group was composed
      of 5 female patients, aged 7- 77 years. They presented with a painless
      subcutaneous mass, which was solitary or multiple and most commonly found on the
      extremities. The duration of disease was between 3 months to 5 years. The
      cultures grew Basidiobolus ranarum. A case of GI entomophthoromycosis was seen in
      a 34 year old man, who presented with dyspepsia, multiple intraabodminal masses
      and peritonitis. Two cases of conidiobolomycosis (rhinofacial zygomycosis) were
      seen. These two patients were male, 26 and 39 years old, and they presented with
      unilateral nasal obstruction from a mass at the inferior turbinate. The cultures
      grew Conidiobolus coronatus. CONCLUSION: Entomophthoromycosis in the northern
      part of Thailand is rare. The disease should be differentially diagnosed by a
      chronic painless tumor. The patients in this review responded very well to the
      recommended therapy.

PMID- 12501901
TI  - Risk factors for Pseudomonas aeruginosa bacteremia in Thai patients.
AB  - A case control study to determine the risk factors for P. aeruginosa bacteremia
      was conducted in patients admitted to Siriraj Hospital in 1998. The case group
      consisted of 65 patients with P. aeruginosa bacteremia. There were 3 control
      groups. 65 patients with E. coli bacteremia, 64 patients with S. aureus
      bacteremia and 65 patients without bacteremia. Demographic information and
      potential risk factors i.e. type of infection, associated diseases/conditions,
      procedures/surgery, previous/current use of antibiotics and previous/current use
      of immunosuppressive/cytotoxic agents were extracted from the patients' medical
      records and compared. Univariate analysis revealed that the factors associated
      with P. aeruginosa bacteremia were infections acquired while hospitalized,
      hematologic malignancy, neutropenia, COPD, antibiotic receivers, cytotoxic agents
      receivers. However, multivariate analysis revealed that only hematologic
      malignancy, infections acquired while hospitalized and previous use of parenteral
      antibiotics were risk factors for P. aeruginosa bacteremia.

PMID- 12501902
TI  - Outcome of inguinal hernia repair total extraperitoneal laparoscopic hernia
      repair versus open tension free repair (Lichtenstein technique).
AB  - BACKGROUND: Result and efficacy of laparoscopic hernioplasty has been
      controversial. Many techniques have been performed and evaluated. Totally
      extraperitoneal laparoscopic hernia repair (TEP) technique has been used for
      laparoscopic hernioplasty in this center. Complications, benefit and efficacy in
      terms of recurrence were studied and compared with open tension free repair
      (Lichtenstein). METHOD: Fifty-five patients with 4 recurrent, 16 bilateral and 35
      unilateral groin hernia underwent laparoscopic hernioplasty by the TEP technique.
      The other twenty-four patients with I recurrent 2 bilateral and 21 unilateral
      groin hernia underwent Lichtenstein hernioplasty (OH). Operative time,
      complications, hospital stay and recurrence after 1 year follow-up were recorded.
      RESULT: Mean operative time was 67.85 +/-21.66 and 55.85 +/- 10.60 minutes. Mean
      difference was 12.00, 95 per cent CI (1.83, 22.16) p-value 0.02 (TEP and OH).
      Mean hospital stay was 2.71 +/- 1.29 and 2.38 +/- 0.58 days. Mean difference was
      0.33, 95 per cent CI (-0.26, 0.93) p-value 0.27 (TEP and OH) complication rate
      12.7 per cent and 12.5 per cent p-value 0.64 (TEP and OH). Most complications
      were minor such as seroma, hematoma, neuralgia, one case of pubic osteitis needed
      to remove staples and some parts of the mesh. There was one conversion to open
      repair due to large sac and large bowel adherence. There was one recurrence after
      one year follow-up in the laparoscopic group, no major morbidity or mortality in
      this study. CONCLUSION: This study demonstrated that complications of the TEP
      technique were minimal and it was safe to perform. Although the operative time
      was longer and there was one recurrence in the TEP group, that might be because
      of the early learning period for a new surgical procedure

PMID- 12501903
TI  - Posterolateral fusion with autogenous laminospinous process bone graft.
AB  - The results of posterolateral spinal fusion by using autogenous iliac bone graft
      is gold standard. However, there are some undesirable effects at the donor site.
      This study reports the outcome of posterolateral spinal fusion by using an
      autogenous bone graft from the lamina and spinous process. From June 1993 to May
      2001, Decompressive laminectomy, pedicle screw fixation system and posterolateral
      fusion were performed on 92 patients using autogenous bone from the decompressive
      laminectomy procedure. The follow-up periods were 2-8 years. 97.56 per cent of
      the patients had a solid fusion mass at 6 months after operation. There were no
      undesirable effects at the iliac region. The JOA score for low back pain improved
      in all patients. The result of posterolateral spinal fusion by using autogenous
      bone from the lamina and spinous process is comparable to the autogenous iliac
      bone graft. The advantages of using the laminospinous process bone graft are
      short operating time, less blood loss than taking a bone graft from the iliac
      crest, no complication or undesirable effects at the iliac region.

PMID- 12501904
TI  - Blood pressure response to antihypertensive agents related to baseline blood
      pressure.
AB  - Prevalence of white-coat hypertension varies approximately 20 per cent among mild
      hypertensives. When white-coat hypertensives are prescribed antihypertensive
      medication, there is usually a decrease in clinic blood pressure (BP), but little
      or no change in 24 hours blood pressure (ABPM). The objective of the study was to
      test the hypothesis that efficacy of medication therapy for hypertension is
      identical in any grading of severity of baseline blood pressure. The authors
      retrospectively analysed ABPM data from mild to moderate hypertensive patients.
      Efficacy in decreasing blood pressure by antihypertensives has linear relation to
      baseline blood pressure. Response to antihypertensive agents in white-coat
      hypertension is minimal but a significant effect still persists and the
      possibility of hypotensive adverse events from medication in the case cannot be
      overlooked.

PMID- 12501905
TI  - Bioequivalence study of generic acyclovir compared with the brand name acyclovir.
AB  - The bioequivalence study of 200-mg generic acyclovir was conducted in healthy
      males. The reference Zovirax and the test Zevin were administered as a single
      oral dose after an overnight fast in a two-period, crossover design separated by
      1 week. Serial blood samples were collected over a period of 24 hours. Plasma
      acyclovir concentrations were determined by HPLC and the pharmacokinetic
      parameters were analyzed by non-compartmental analysis. RESULTS: The t 1/2 for
      the test (4.5 +/- 2.4 h) and Zoviraxl (3.9 +/- 2.6 h) were comparable. The
      analysis of variance was carried out and the median Tmax (1.50 h) for the test
      was not statistically difference from Zovirax. The mean (90% CI) of the AUC0
      infinity and the Cmax ratios for (Test/reference) were 0.95 (0.83-1.09) and 0.95
      (0.83-1.10), respectively. These values fell within the bioequivalence criteria
      of 0.80-1.25, thus it was concluded that Zevin and Zovirax were bioequivalence.

PMID- 12501906
TI  - Ileal atresia and total colonic aganglionosis.
AB  - Herein, the authors report a case of ileal atresia who failed to have good bowel
      function after primary anastomosis. After the leakage of the revised anastomosis,
      a thorough pathological review found distal aganglionosis. An ileostomy followed
      by an ileocolic patch operation were performed for temporary decompression,
      awaiting intestinal adaptation. A definitive pull-through was performed, eight
      months later. The child also had bilateral cleft lip together with complete cleft
      palate, and hemivertebrae of the thoracic spines. A cluster of malformations is
      unusual in a single patient.

PMID- 12501907
TI  - Clomipramine-resistant, fluoxetine-responsive obsessive compulsive disorder: a
      case report.
AB  - Serotonin re-uptake inhibitors (SRIs), clomipramine and selective serotonin re
      uptake inhibitors (SSRIs), are the first-line pharmacologic therapies for
      patients with obsessive compulsive disorder (OCD). However, 40 to 60 per cent of
      patients do not respond to adequate treatment trials of SRIs. SRI partial- and
      non-responders must be treated with augmentation strategies or put on another SRI
      since non-response to the first SRI does not necessarily indicate a non-response
      to a second SRI. Each treatment trial should run at least 10 weeks and if
      successful, the drug should be continued for at least 1 to 2 years and withdrawn
      gradually. The presented patient had a second episode of OCD which was resistant
      to more than 10 weeks of high dosage clomipramine even though he responded very
      well during the first episode 4 years earlier and had been off clomipramine for 3
      years. Augmentation to clomipramine with lithium and then haloperidol
      consecutively also failed. When clomipramine was changed to fluoxetine, the OCD
      symptoms were responsive even at a starting dosage of 20 mg/day. The response
      improved as the dosage of fluoxetine was increased. The response reached a
      maximum and the patient coped very well in every aspect of daily life when the
      dosage of fluoxetine was increased to 60 mg/day. He had taken fluoxetine at this
      daily dosage for one year before the drug was tapered off. It has now been more
      than two years since he has had any OCD symptoms and clomipramine was terminated.

PMID- 12501908
TI  - Detection of JC virus infection in progressive multifocal leukoencephalopathy:
      the first documented case in Thailand.
AB  - Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating brain disease
      caused by human polyoma JC virus (JCV). This disease is an important cause of
      morbidity and mortality in AIDS patients. Definite diagnosis currently requires a
      brain biopsy. PCR for JCV of CSF, an emerging diagnostic tool, has a high
      specificity for the diagnosis of PML in patients with characteristics on clinical
      and neuroradiological findings. The authors report a 36-year-old woman who
      presented with prolonged fever, progressive weakness, and slow speech for 2
      months. Clinical features and MRI findings were compatible with PML. Qualitative
      PCR for JCV of CSF showed a positive result. This report emphasizes the yield of
      PCR, the CSF for JCV in a diagnosis of PML, which may reduce the need for a brain
      biopsy in such cases.

PMID- 12501910
TI  - Oral fluid testing for drugs of abuse: positive prevalence rates by Intercept
      immunoassay screening and GC-MS-MS confirmation and suggested cutoff
      concentrations.
AB  - Draft guidelines for the use of oral fluid for workplace drug testing are under
      development by the Substance Abuse and Mental Health Services Administration
      (SAMHSA) in cooperation with industry and researchers. Comparison studies of the
      effectiveness of oral fluid testing versus urine testing are needed to establish
      scientifically reliable cutoff concentrations for oral fluid testing. We present
      the results of the first large scale database on oral fluid testing in private
      industry. A total of 77,218 oral fluid specimens were tested over the period of
      January through October 2001 at LabOne. Specimens were screened by Intercept
      immunoassay at manufacturer's recommended cutoff concentrations for the five
      SAMHSA drug categories (marijuana, cocaine, opiates, phencyclidine, and
      amphetamines). Presumptive positive specimens were confirmed by gas
      chromatography-tandem mass spectrometry. A total of 3908 positive tests were
      reported over the 10-month period, representing a positive rate of 5.06%. Of the
      five drug categories, marijuana and cocaine accounted for 85.75% of the
      positives. The pattern and frequency of drug positives showed remarkable
      similarity to urine drug prevalence rates reported for the general workforce
      according to the Quest Diagnostics' Drug Testing Index over the same general
      period, suggesting that oral fluid testing produces equivalent results to urine
      testing. The data on oral fluid testing also revealed a surprisingly high 66.7%
      prevalence of 6-acetylmorphine confirmations for morphine positives suggesting
      that oral fluid testing may be superior in some cases to urine testing.
      Comparison of oral fluid drug concentrations to SAMHSA-recommended cutoff
      concentrations in Draft Guidelines indicated that adoption of the screening and
      confirmation cutoff concentrations of Draft Guidelines #3 would produce the most
      consistent reporting results for all drug classes except amphetamines.
      Consequently, it is suggested that the final Guidelines adopt the screening and
      cutoff concentrations listed in Draft Guidelines #3 with the exception of
      lowering the amphetamines cutoff concentrations (screening/confirmation) to 50/50
      ng/mL for amphetamine and methamphetamine.

PMID- 12501911
TI  - Disposition of cocaine in skin, interstitial fluid, sebum, and stratum corneum.
AB  - The aim of this study was to determine whether or not the skin acts as a
      reservoir for cocaine. Cocaine-d5 (1 mg/kg) was administered to five
      nondependent, cocaine-experienced volunteers. Skin tissue, interstitial fluid,
      sebum, stratum corneum, and plasma were collected for 72 h after drug
      administration. Cocaine and benzoylecgonine (BE) levels were determined using GC
      MS. Cocaine concentrations peaked in plasma at 1 h after administration, with
      pharmacokinetic parameters (t(1/2), CL, Vd) also in the expected ranges. In skin,
      cocaine levels peaked around 1.5 h after administration and became undetectable
      by 6 h. A correlation was found between the plasma and skin AUC for cocaine (R =
      0.99, p = 0.006, N = 4). BE was not detected in skin. In interstitial fluid (N =
      4), cocaine concentrations peaked around 5 h after drug administration and were
      undetectable by 24 h. BE peaks varied between 2 and 24 h and were not detectable
      at 48 h. In sebum, cocaine levels peaked between 3 and 24 h. BE was found in
      three samples between 12 and 24 h. In stratum corneum, cocaine was measurable in
      only one sample from one subject. These findings suggest that skin does not act
      as a reservoir for cocaine. Rather, cocaine appears to be distributed rapidly to
      the skin and eliminated, following a time course similar to that of plasma.

PMID- 12501912
TI  - Fully automated determination of cannabinoids in hair samples using headspace
      solid-phase microextraction and gas chromatography-mass spectrometry.
AB  - This paper describes a fully automated procedure using alkaline hydrolysis and
      headspace solid-phase microextraction (HS-SPME) followed by on-fiber
      derivatization and gas chromatographic-mass spectrometric (GC-MS) detection of
      cannabinoids in human hair samples. Ten milligrams of hair was washed with
      deionized water, petroleum ether, and dichloromethane. After the addition of
      deuterated internal standards the sample was hydrolyzed with sodium hydroxide and
      directly submitted to HS-SPME. After absorption of analytes for an on-fiber
      derivatization procedure the fiber was directly placed into the headspace of a
      second vial containing N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) before
      GC-MS analysis. The limit of detection was 0.05 ng/mg for delta9
      tetrahydrocannabinol (THC), 0.08 ng/mg for cannabidiol (CBD), and 0.14 ng/mg for
      cannabinol (CBN). Absolute recoveries were in the range between 0.3 and 7.5%.
      Linearity was proved over a range from 0.1 to 20 ng/mg with coefficients of
      correlation from 0.998 to 0.999. Validation of the whole procedure revealed
      excellent results. In comparison with conventional methods of hair analysis this
      automated HS-SPME-GC-MS procedure is substantially faster. It is easy to perform
      without use of solvents and with minimal sample quantities, but with the same
      degree of sensitivity and reproducibility. The applicability was demonstrated by
      the analysis of 25 hair samples from several forensic cases. The following
      concentration ranges were determined: THC 0.29-2.20 (mean 1.7) ng/mg, CBN 0.55
      4.54 (mean 1.2) ng/mg, and CBD 0.53-18.36 (mean 1.3) ng/mg. 11-nor-Delta9
      tetrahydrocannabinol-9-carboxylic acid could not be detected with this method.

PMID- 12501913
TI  - Acetylcodeine as a urinary marker to differentiate the use of street heroin and
      pharmaceutical heroin.
AB  - Acetylcodeine (ACOD) is a synthesis byproduct present in street heroin but not in
      pharmaceutical diacetylmorphine (DAM) as used in the Swiss program Heroin
      Assisted Treatment for Opiate Dependent Drug Users (HAT). ACOD was evaluated and
      validated as an urine marker to detect the consumption of street heroin by HAT
      participants. A gas chromatography-mass spectrometry method allowing the
      quantitation of ACOD concentrations as low as 0.2 ng/mL urine has been developed.
      In opiate-naive subjects, intravenous (i.v.) ACOD showed a plasma elimination
      half-life of 237 +/- 18 min, urine peak concentrations 2 h after administration,
      and a detection window of 8 h. Only 0.4 +/- 0.1% was excreted unchanged, with
      codeine (COD) as the main metabolite. ACOD may be formed by transacetylation when
      i.v. DAM and oral codeine are co-administered. To avoid false-positive results,
      the calculation of COD/ACOD ratios is recommended. In a study with 105 HAT
      participants, 14% of the tested urines were ACOD positive. Only a low correlation
      was found between the anonymously self-declared consumption of street heroin and
      the ACOD positive rate.

PMID- 12501914
TI  - Studies on in vitro degradation of anhydroecgonine methyl ester
      (methylecgonidine) in human plasma.
AB  - The presence of the cocaine pyrolysis product anhydroecgonine methyl ester (AEME,
      methylecgonidine) in plasma indicates the smoking of cocaine. The stability of
      this analyte in human plasma has not been studied. In the present investigation
      AEME and its hydrolysis product anhydroecgonine (AE, ecgonidine) were assayed in
      plasma and buffers using gas chromatography-mass spectrometry. It was found that
      50% of AEME in human plasma was hydrolyzed to AE within 5 days at room
      temperature and within 13 days at 4 degrees C. Addition of esterase inhibitors
      such as sodium fluoride or echothiophate iodide reduced the hydrolysis
      significantly. Hydrolysis of AEME also occurred in buffers with pH values above
      5, but the hydrolysis rate was significantly lower when compared with plasma and
      could be markedly increased by the addition of butyrylcholine esterase. The data
      suggest that AEME is degraded via two mechanisms: chemical hydrolysis at basic pH
      and enzymatic hydrolysis by butyrylcholine esterase. Therefore, proper storage
      conditions must be provided for the assay of AEME in plasma.

PMID- 12501915
TI  - In vitro production of gamma-hydroxybutyrate in antemortem urine samples.
AB  - The in vitro production of gamma-hydroxybutyrate (GHB) in antemortem urine
      samples was demonstrated over an eight-month period. Positive chemical ionization
      gas chromatography-mass spectrometry (PCI-GC-MS) was used to detect trace amounts
      of GHB produced in vitro under certain storage conditions. Freshly prepared drug
      free human urine was stored at 21, 4, and -20 degrees C in the presence of
      preservative. Although artifactual production of GHB occurred more rapidly at
      elevated temperatures, the presence of an antimicrobial agent (sodium azide) in
      the drug-free urine control did not impede GHB production. The preliminary data
      suggest that although in vitro production was demonstrated, the elevations in
      concentration were nominal and less than 5 mg/L for all conditions tested over
      the 244-day period. These preliminary data suggest that urine samples should be
      preserved and stored at -20 degrees C to minimize artifactual GHB production.
      Most importantly, conditions of storage and preservative should also be taken
      into consideration when interpreting GHB results that are close to the
      administrative cutoff. In order to establish the distribution of GHB
      concentrations in routine forensic case samples, a series of 100 antemortem urine
      samples, in which GHB was not suspected, was analyzed. Samples were preserved
      with sodium fluoride (1%) and had been stored for up to one year at room
      temperature. Although concentrations as high as 7 mg/L were measured in some
      samples, the mean and median concentrations were 1.8 mg/L and 1.6 mg/L,
      respectively. Even following storage at room temperature for an extended period,
      more than 95% of the urine samples contained less than 5 mg/L GHB and 100%
      contained less than 10 mg/L. An administrative cutoff of 10 mg/L in antemortem
      urine was used for routine antemortem casework.

PMID- 12501916
TI  - Determination of delta9-THC in whole blood using gas chromatography-mass
      spectrometry.
AB  - A simple and reliable liquid-liquid extraction method for the determination of
      delta9-tetrahydrocannabinol (THC) in whole blood utilizing gas chromatography
      mass spectrometry in electron impact mode is described. The substance is
      derivatized with pentafluoropropionic anhydride in pentafluropropanol. The limit
      of detection is 0.5 ng/mL for a 1-mL specimen, with recovery greater than 70%.
      The intra-assay coefficient of variation (CV) is 3.1% to 5.2%, and the interassay
      CV is 6.4% to 9.5%, calculated at THC concentrations of 1, 5, and 25 ng/mL. The
      accuracy is between 95 and 97%. The optimization of extraction and derivatization
      conditions is detailed.

PMID- 12501917
TI  - A single therapeutic treatment with betamethasone is detectable in hair.

PMID- 12501918
TI  - A new series of hair analyses from Napoleon confirms chronic exposure to arsenic.

PMID- 12501919
TI  - Tuberculosis in children--what has changed in last 20 years?
AB  - Several changes have been observed in the epidemiology, clinical manifestations,
      diagnostic modalities and treatment of tuberculosis. Emergence of HIV epidemic
      and drug resistance have posed significant challenges. With increase in number of
      diseased adults and spread of HIV infection, the infection rates in children are
      likely to increase. It is estimated that in developing countries the annual risk
      of tuberculosis infection in children is 2.5%. Nearly 8-20% of the deaths caused
      by tuberculosis occur in children. Lymph node tuberculosis has increased over
      last two decades. HIV infected children are at an increased risk of tuberculosis,
      particularly disseminated disease. In last two decades drug resistant
      tuberculosis has increased gradually. The rates of drug resistance to any drug
      varied from 20% to 80% in different geographic regions. Various diagnostic
      techniques such as improved culture techniques, serodiagnosis, and nucleic acid
      amplification have been developed and evaluated to improve diagnosis of childhood
      tuberculosis. Serodiagnosis is an attractive investigation but till date none of
      the tests have desirable sensitivity and specificity. Tests based on nucleic acid
      amplification are a promising advance. Relatively less experience in children,
      need for technical expertise and high cost are limiting factors for their use in
      children with tuberculosis. Short-course chemotherapy for childhood tuberculosis
      is well established. Treatment with intermittent regimens is comparable to daily
      regimens. Directly observed treatment strategy have shown encouraging result.

PMID- 12501920
TI  - Improving bacteriological diagnosis of tuberculosis.
AB  - This review is to summarize recent developments in the field of mycobacteriology
      since the diagnosis of tuberculosis remains elusive in spite of our best efforts
      and great scientific advances. Progress has been made in further improving upon
      the age old, time tested traditional techniques like microscopy (Auramine
      Rhodamine Fluorescent staining and peptide nucleic acids), culture and
      sensitivity techniques (solid, liquid, radiometric, and non-radiometric systems)
      that still remain as the gold standard for its diagnosis. Development of rapid
      methods [(high performance liquid chromatography, thin layer chromatography, RNA
      sequencing and polymerase chain reaction (PCR), nucleic acid sequence based
      amplification assay (NASBA), Transcription mediated assay (TMA) and Ligase chain
      reaction (LCR)] have paved the way for its rapid detection and treatment. It is
      interesting to see the role of molecular assays appearing more often in
      literature now. The molecular amplification systems (PCR, NASBA, TMA, LCR)
      besides identifying Mycobacterium tuberculosis (MTB) as well as non-tuberculous
      mycobacteria (NTM), directly from the sample can also identify Rifampin (rpoB
      gene)/Isoniazide (katG gene) resistant strain. Molecular assays have been found
      useful particularly in smear positive sputum with high sensitivity and
      specificity whereas variable sensitivity for sputum negative and extra pulmonary
      specimens has been observed. Representative specimen and its quality affect the
      performance of these assays. Emphasis should given to proper collection and
      transportation of the representative specimen for appropriate evaluation.

PMID- 12501921
TI  - PCR diagnosis of tuberculosis--experience in India.
AB  - Rapid and accurate diagnosis of tuberculosis is the cornerstone of global
      tuberculosis control programmes. With increasing incidence of tuberculosis
      epidemics, the low sensitivity and the length of time taken by traditional
      diagnostic modalities have hampered the efforts to interrupt disease
      transmission. Introduction of Polymerase Chain Reaction has enhanced the
      diagnostic predictability of the disease especially in the extrapulmonary,
      paucibacillary samples. High specificity and sensitivity have been reported in
      different samples. The technique is capable of picking as few as ten to fifty
      tubercle bacilli. When PCR technique is performed under quality controlled
      conditions, false negatives (due to underfined polymerase inhibitors) and false
      positives (due to cross contamination during sample collection or in the
      laboratory) can easily by avoided. Samples from sites with a possible latent
      infection focus or DNA from dead bacilli may give a positive reaction. The use of
      PCR with traditional diagnostic tools along with clinical presentation can prove
      helpful in patients presenting with a diagnostic dilemma.

PMID- 12501922
TI  - Genetic basis of tuberculosis susceptibility in India.
AB  - Tuberculosis is a complex disease resulting from the responses of immunological,
      genetic and environmental factors to the chronic infectious agent, Mycobacterium
      tuberculosis. Several genetic factors have been implicated in host disease
      susceptibility and the prevalence of a disease in a population may be equal to
      the product of the frequencies of the susceptible alleles present in the
      population living in an endemic area. The endogamous, sympatrically isolated gene
      pools, exposed to the highly infectious environmental load of India, is an ideal
      model to study tuberculosis susceptibility. Our recent studies in this endemic
      region have reiterated the association of HLA-DRB1*02 and its subtype DRB1*1501
      with tuberculosis susceptibility and have identified an IL-10 associated disease
      susceptibility in HLAnon-DRB1*02, BCG scar negative individuals and a skewed
      usage of TCR Vb in BCG scar negative, HLA high risk allele carrying individuals.
      This indicates that there may be several pathways leading to disease.
      Tuberculosis susceptibility is not thus a one-gene one product manifestation but
      multifactorial and epistatic influences of various factors finally lead to the
      disease. We review the factors that has been explored under Indian context in
      tuberculosis susceptibility.

PMID- 12501923
TI  - Genomic study of Mycobacterium tuberculosis and its clinical applications.
AB  - The availability of the complete genome sequence of Mycobacterium tuberculosis
      has provided us with unprecedented opportunities for understanding the biology of
      this highly successful pathogen and its unique interaction with the host. It is
      hoped that the impetus so provided to mycobacterial research will accelerate the
      development of effective and novel strategies for the treatment, prevention and
      detection of tuberculosis.

PMID- 12501924
TI  - Aspiration cytology for diagnosis of tuberculosis--perspectives in India.
AB  - Tuberculosis (TB) a common cause of mortality can readily be diagnosed by fine
      needle aspiration. The technique is a simple, cost effective, out patient
      procedure with a high diagnostic accuracy both in adults and children. The
      diagnostic morphologic findings comprise of epithelioid cell granulomas and giant
      cells with or without necrosis. Often an acute inflammatory exudate is obtained.
      Stain for acid fast bacilli immensely augments diagnosis especially in cases
      where necrosis or an inflammatory exudate is obtained. Culture studies on
      aspirated material are time consuming though diagnosis is enhanced. PCR can be
      applied to detect mycobacterial DNA and has been applied on aspirated material
      and found to be more sensitive in the detection of tuberculosis. In children TB
      of lymph nodes is readily identified and so also from other sites such as bone
      and soft tissues. In children FNAC also plays a role in detection of BCG
      adenitis, infection with atypical mycobacteria and co-existing infections such as
      HIV and AIDS.

PMID- 12501925
TI  - Basic concepts in the treatment of tuberculosis.
AB  - Early diagnosis and prompt treatment of tuberculosis is important in order to
      minimize complications and sequelae. It is important to select the proper regimen
      and ensure that the patient is getting adequate number of drugs for adequate
      duration. The principles of short course chemotherapy and the rationale behind
      the currently recommended regimens are outlined in this article. Standard (daily
      or intermittent) 6-month short course regimens are sufficient to cure most forms
      of tuberculosis in children and only severe forms like miliary, meningitis and
      neuro-tuberculosis require a longer duration of treatment. Worldwide, the
      (directly observed therapy) DOTS strategy is now recommended in the order to
      ensure cure and cut down the transmission of disease in the community and
      wherever possible, should be employed in the treatment of tuberculosis in
      children also.

PMID- 12501926
TI  - Priorities in tuberculosis research in India.
AB  - India accounts for nearly 30% of all tuberculosis cases in the world today and
      more adults in India die from TB than from any other infectious disease. The
      problems of HIV and multidrug resistance will make tuberculosis epidemic in India
      much worse unless urgent action is taken. DOTS is being applied on individual
      basis in the country. Maintaining the momentum in order to achieve national
      coverage in a phased manner, while maintaining the quality of services will
      require constructive commitment from all sectors, both within and outside
      government. This much be accompanied by additional research inputs and critical
      data analysis. Operational research provides programme managers the data and
      tools they need to analyse continuously improve services they offer, hence this
      must be strengthened with an overall aim to improve diagnosis and treatment of TB
      patients by translating the results of research into policy and practice. At the
      same time one should aim to strengthening biomedical research which promises
      convenient diagnostic tests, new and cost effective drugs and safe an effective
      vaccines, shortening of treatment, improved treatment of latest infection and
      overcoming threat of MDR-TB. The challenge is how to achieve this formidable goal
      as well as gear up to efficiently handle the growing burden of HIV-TB infected
      patients. The key to success lies in making available to all what we already
      have, by strengthening operational aspects of programme and at the same time not
      focus on the research efforts being done in basic science. The solution lies in
      the link between basic science and public health.

PMID- 12501927
TI  - A short retrospection.

PMID- 12501928
TI  - Nerve conduction velocity and spinal reflexes may change in rats after fumonisin
      B1 exposure.
AB  - Mycotoxin fumonisin B1 (FB1) a natural inhibitor of ceramide synthase
      contaminating mainly the corn-based food and feed may cause dysfunctions in the
      nervous system. In the present study peripheral neural dysfunctions were
      biomonitored after dietary FB1 exposure in rats. Daily oral doses of 6.2 mg/kg
      body weight/day FB1 were applied in rats for 2 weeks. Before and after FB1
      treatment nerve conduction velocities of tibial and sciatic nerves and spinal
      reflexes were analyzed in vivo. Electrophysiological recordings of biphasic
      plantar EMG (M and H components) and evaluation of sensory and motor nerve
      conduction velocities were carried out. Nerve conduction velocities revealed
      decreasing tendencies after FB1 exposure. The flexor reflex and the H-components
      of the extensor reflex were significantly reduced. The proposed in vivo
      biomonitoring can reveal functional impairment of the peripheral nervous system
      caused by mycotoxin exposure. Reduction of conduction velocity and altered
      reflexes after FB1 exposure are suspected to be associated with modified signal
      transmission due to toxic systemic effects and possible changes in sphingolipid
      metabolism.

PMID- 12501929
TI  - Discomfort: not pain but still unpleasant feelings from the gut.
AB  - Most of the factors initiating food or fluid intake have already been studied,
      but much less is known about those terminating ingestion. We have hypothesised
      that discomfort originating from the gastrointestinal system may be one of those
      factors. Gut distension cause pain if the intestinal volume changes but merely
      discomfort if only the tension of the gut wall increases. It seems that mild
      unpleasantness (i.e. discomfort) arising from the gut as a result of moderate
      (quasi-isometric) distension, among and in concordance with other factors, may
      significantly reduce intake and hence contribute to physiological satiety. The
      arising discomfort can be detected by measuring the amount and rate of the
      ingestion, by recording and analysing ingestive behavior by taste-aversivity and
      taste-reactivity tests, etc. Conclusions of all experiments point to the same
      direction: tension increase in the gut wall causes discomfort and results in
      decrease of intake, i.e. satiety.

PMID- 12501930
TI  - Effect of orexin-A on discharge rate of rat suprachiasmatic nucleus neurons in
      vitro.
AB  - The suprachiasmatic nuclei (SCN) constitute the principal pacemaker of the
      circadian timing system in mammals. The generated rhythm is forwarded mostly
      through projections to various hypothalamic nuclei. On the other hand, the
      regulated processes feedback to the SCN. One of the possible feedback pathways is
      the orexinergic projection from the lateral hypothalamus. Orexins are recently
      identified neuropeptides with an overall facilitatory effect on waking behaviors.
      Orexinergic fibers are widely distributed throughout the brain and are also
      present in the SCN. In this study we examined the effect of orexin-A on the
      spontaneous activity of rat SCN cell in vitro. Neurons showed 2 different firing
      pattern (continuous-regular, intermittent-irregular). Orexin-A increased firing
      rate in both cell types at 10(-8) M concentration, but caused a clear suppression
      of neuronal activity at 10(-7) M. Continuously firing neurons were less
      responsive than those firing intermittently. These results show that orexin-A may
      play a role in the modulation of the circadian pacemaker function. The
      neuropeptide might exert both direct, postsynaptic effects on SCN neurons and
      indirect, presynaptic effects on excitatory and inhibitory terminals. The dose
      dependent modification of the firing rate indicate that the weight of these
      factors changes with the concentration of orexin-A.

PMID- 12501931
TI  - Comparison of single NMDA receptor channels recorded on hippocampal principal
      cells and oriens/alveus interneurons projecting to stratum lacunosum-moleculare
      (O-LM cells).
AB  - NMDA receptors participate in the glutamatergic excitation of both principal
      cells and GABAergic interneurons. The features of NMDA channels on specific
      interneurons, however, are not known. Therefore, we obtained direct measurements
      of single NMDA receptor channels on anatomically identified oriens/alveus
      interneurons projecting to stratum lacunosum-moleculare (O-LM cells) and compared
      them to those found on hippocampal principal cells using cell-attached recordings
      in in vitro slice preparations. The recorded channels could be blocked by
      ketamine, a membrane-permeable NMDA channel inhibitor. In the absence of Mg(2+),
      all O-LM cells had NMDA channels with a comparable slope conductance
      (approximately 60pS) to those measured on CA1 pyramidal cells or dentate granule
      cells. In addition, NMDA channels with smaller conductance (43-45 pS) were also
      found on two O-LM cells but not on principal cells. These results suggest that at
      least two types of NMDA channels are expressed on O-LM cells likely reflecting
      distinct subunit composition.

PMID- 12501932
TI  - Frequency of gamma activity is modulated by motivation in the auditory cortex of
      cat.
AB  - Repetitive acoustic stimuli elicit steady-state response (SSR) in the gamma-band
      both in humans and in mammals. Our aim was to investigate changes of the
      spontaneous gamma activity and the SSR in the auditory cortex of cats in the
      background of an instrumental conditioning situation. Epidural electrodes were
      chronically implanted above the auditory neocortex. The presentation rate of the
      clicks varied between 20 and 65/s. Spontaneous EEG and SSR were collected in
      three behavioral states: in an indifferent environment, in the instrumental cage
      while the cat was waiting for the light CS, and when she stepped on the pedal and
      was waiting for the meat reward. Using different repetition rate clicks we
      determined which stimulus rate elicited the largest SSR in these three
      situations. In quiet animal the highest SSR appeared at 28-30/s. Before and
      during the CS the optimal stimulus rate shifted to 32-38/s. The frequency of the
      spontaneous gamma activity changed in parallel way depending on the situation. We
      conclude that both the SSR and the spontaneous gamma activity reflect resonant
      activity of the same neuronal circuit of the auditory cortex, and it is modulated
      by the motivational state of the animal.

PMID- 12501933
TI  - Effect of sub-lethal concentrations of aluminium on the filtration activity of
      the freshwater mussel Anodonta cygnea L. at neutral pH.
AB  - Significant amounts of aluminium (Al) are commonly present in rivers and lakes,
      largely in particulate form in neutral waters. Freshwater bivalves, as filter
      feeders are therefore exposed to both particulate and dissolved metal and are
      potentially vulnerable to Al. The effect of Al on filtering behaviour of the
      freshwater mussel Anodonta cygnea L. was investigated during short (1 hour) and
      long-term (15 days) exposure to environmentally relevant concentrations (250 and
      500 microg l(-1)) at neutral pH. Water flow through the outflow siphon was
      monitored as an indicator of pumping capacity. Short-term (1 hour) exposure to
      500 microg l(-1) added Al produced an irreversible decrease in the duration of
      filtering periods, presumably as an avoidance response to the toxicant. One-hour
      exposure 250 microg l(-1) Al had no detectable effect. When mussels were exposed
      to 250 or 500 microg l(-1) added Al for 15 days, siphon activity measured in days
      11-15 of exposure was inhibited by 50% and 65%, respectively, compared to pre
      exposure levels. Recovery occurred following transfer of mussels to
      uncontaminated water. Interaction between Al and freshwater bivalves at neutral
      pH may affect both the performance of the mussels and the chemical speciation of
      the metal in the natural environment.

PMID- 12501934
TI  - DNA profiling by detection of repetitive nucleotide sequences on human chromosome
      6.
AB  - Genetic/genomic polymorphism, i.e. variations in DNA sequences are ideally
      assayed by direct nucleotide sequencing of a gene region or other homologous
      segment of the genome. An easier and cheaper approach, however, if the variants
      are analyzed by hybridization technology using restriction fragment length
      polymorphisms (RFLPs) or by detection of the number of tandem repeats (VNTR) of
      small DNA segments, the "minisatellites". In this study we describe results of
      the DNA analysis of repetitive sequences of human 6th chromosome by the
      application of a chemiluminescent labeled probes. The allele frequency
      distribution of polymorphic DNA sequences has been determined in unrelated
      individuals. The isolated genomic DNA was cut with Pst I restriction enzyme, size
      fractionated on agarose gel and hybridized with a chemiluminescent labeled D6
      S132 probe. At this locus the Pst I cleaved DNA fragments are ranging from 1841
      to 6098 base pairs (bp). Specific genetic pattern was characterized by more
      frequent fragments (3313 and 3884 bp), and the rarely occurring ones (clustered
      between 1841-2595 and 5227-6098 bp). Our study provides a further possibility for
      characterization of individual genomic patterns.

PMID- 12501935
TI  - Hypnotic susceptibility and alterations in subjective experiences.
AB  - Pavlov has described hypnosis as a partial sleep. A contemporary approach to this
      altered state of consciousness will be discussed. Under laboratory conditions
      subjective and behavioral data will be analyzed after hypnotic induction,
      shamanic trance and relaxation with listening to music. Role of different
      cortical regions will be shown after different hypnotic inductions as a function
      of hypnotic susceptibility. The importance of context will be underlined as an
      important factor in the possible alteration of consciousness.

PMID- 12501936
TI  - Interoception, body perception and awareness. The heritage of Gyorgy Adam.
AB  - Two series of studies are reported dealing with (1) psychophysical
      characteristics and (2) interactions of visceroceptive and somatosensoric
      information processing. The first studies characterized detection, graduation and
      localisation of visceral as compared to somatic stimuli. The second series
      investigated somatovisceral discrimination, masking, and summation at different
      levels of awareness. METHODS: Distension of the sigmoid colon served as standard
      model. The visceral stimulus was applied by a balloon probe in the sigmoid colon,
      the external abdominal stimulus by a ring-shaped stimulator at two abdominal
      sites. A forced-choice-paradigm with two observation intervals was applied
      (multiple staircase) to estimate interactions between somatosensation and
      visceroception. RESULTS: The visceral distension stimulus can be detected or
      discriminated correctly without conscious sensation. Visceral localization of
      stimuli requires conscious sensation. Combining visceral and somatic stimuli
      resulted in distinct elevation of visceral thresholds demonstrating somatosensory
      masking of the visceral stimulus. There are characteristic somato-visceral and
      viscero-somatic differences in masking and qualitative differences between
      implicit and explicit processing stages. Specific electrocortical reactions to
      visceral stimuli could be shown. DISCUSSION: Visceroception is represented on the
      highest functional level as a fairly independent submodality of body perception.
      There are several hints that visceroception and protopathic somatic sensitivity
      follow the same major paths and comprise the same ontogenetic origin. Perceptual
      interactions are determined by modality and awareness and depend on the task. The
      role of implicit and explicit body perception considering the body self and its
      significance in the context of consciousness are discussed.

PMID- 12501937
TI  - Does dog-human attachment affect their inter-specific cooperation?
AB  - Leading a blind or blindfolded person is a complex cooperative task influenced by
      many factors. The aim of this study was to determine if quality of attachment
      affects the performance of dog and owner dyads showed on an Obstacle Course.
      Modified Ainsworth's Strange Situation Test was used for assessing attachment
      quality. Only one dimension of the attachment, the 'anxiety' factor was found to
      correlate with behavioural measures of the Obstacle Course (e.g. number of
      mistakes, initialisation index that reflects which participant initiates more
      actions in a dyad). We found significant differences of performance between the
      three groups of dog-owner pairs (pet dog, guide dog and police dog dyads), but we
      could not show significant differences in the 'attachment' factor among these
      groups. We concluded that it is not the attachment type that causes the main
      differences in the leading behaviour of our three study groups. Dogs have an
      innate ability for cooperation with humans that was enhanced by selective
      breeding during domestication and this basic ability can be modified by training
      but seem to be less affected by the relationship with the owner.

PMID- 12501938
TI  - Modulation and experience of external stimuli: toward a science of experience and
      interoception.
AB  - The concept of interoception can be found in various writing over the past 100 or
      more years dating back to Sherrington, James and Lange. Professor Gyorgy Adam
      that made American scientists increasingly aware of the importance of
      interoception with his 1967 book Interoception and Behavior. In this article we
      want to discuss two areas of research from out laboratory that have been
      influenced from this perspective. First, we will focus on electrocortical
      correlates of error detection during visuo-motor task and examine the manner in
      which an individual becomes aware of making an error as well as the way in which
      this awareness directs behavior on an ongoing basis. Second, we will examine
      hypnotic modulation of the pain experience and describe the manner in which
      electrocortical processes reflect the modulation and experience of pain. In this
      discussion, we suggest the importance of the anterior cingulate in not only
      modulating these processes in particular but also in its more general role as an
      interface between the limbic system and the neocortex and the integration of
      cognitive with emotional stimuli.

PMID- 12501939
TI  - Dynamics of acoustical evoked potentials on a background of habituation to verbal
      stimulus in persons with different individual anxiety levels.
AB  - Changes in the amplitude and the latencies of peak P300 of acoustical evoked
      potential on a background of the verbal stimulus novelty loss were used for
      determination of the brain activity specifity in individuals with various anxiety
      levels. The increase of the peak P300 latency of acoustical evoked potential on a
      background of trace processes arising after habituation was determined. This
      parameter did not depend on an anxiety level. However, the latency change
      depended on the attentional level to a submitted signal. The peak P300 amplitude
      in the right temporal cortex field was connected with the anxiety level--there
      was a growth of amplitude on a habituation background with the low anxious
      subjects, and with the highly anxious people the changes of this parameter were
      not observed. The anxiety level has rendered influence to dehabituation reaction.
      Dehabituation is observed with the low-anxiety subjects.

PMID- 12501940
TI  - The psychophysiology of nausea.
AB  - Nausea is an unpleasant sensation usually referred to the stomach and sometimes
      followed by vomiting. Little is known about the subjective aspects of nausea
      because like pain and fatigue, it is a private sensation. We conceive of nausea
      as a complex control mechanism that signals us when not to eat. Our research in
      the areas of motion sickness and chemotherapy has led us to propose that we each
      have a dynamic threshold for nausea, which depends on the interaction of inherent
      factors and more changeable psychological factors, and that this threshold
      effects the individual's cognitive appraisal of both the nauseogenic stimulus and
      his/her bodily change in response to the nauseogenic stimulus. Inherent factors
      that are described are age, gender and race; psychological factors that are
      included are anxiety, expectation, anticipation and adaptation. The physiological
      responses that have been found to accompany nausea include an increase in
      sympathetic nervous system activity, a decrease in parasympathetic activity, an
      increase of abnormal dysrhythmic gastric activity, and an increase in plasma
      vasopressin. It is concluded that beneficial selective reduction of nausea will
      depend on a greater knowledge of the interaction of the psychological and
      physiological variables.

PMID- 12501941
TI  - Number of GABA immunonegative and GABA immunopositive neurons in human epileptic
      temporal cortex.
AB  - The number of neurons, both GABA immunopositive and immunonegative, was
      determined in temporal epileptic foci of 7 patients after temporal lobectomy, and
      compared to neuronal numbers in temporal cortex of two controls taken from tumor
      operated patients. The thickness of the cortex of the epileptic cortex diminished
      by about 10%, while the number of nerve cells decreased to 67% of that of the
      control value: it was 19.000/mm(3) vs. 28.000/mm(3) found in the control. This
      decline was due to cell degeneration, which, however, was more severe for non
      GABAergic nerve cells. Accordingly, the proportion of the GABA-positive neurons
      in the otherwise diminished neuronal population increased to 36.4% from the 32%
      control value. The number of GABAergic terminals, however, decreased even
      further, explaining the resulting disinhibition during epileptic seizures.

PMID- 12501942
TI  - Systematic review of conservative interventions for subacute low back pain.
AB  - OBJECTIVE: To evaluate the effect of conservative interventions on clinically
      relevant outcome measures for patients with subacute low back pain. This is
      particularly important because effective treatment for subacute low back pain
      will prevent the transition to chronic low back pain, a condition that is largely
      responsible for the high health care costs of low back pain. DESIGN: Systematic
      review of randomized controlled trials. MAIN OUTCOME MEASURES: Methodological
      quality of each trial was assessed. Effect sizes and 95% confidence intervals
      were calculated for pain and disability and risk ratios for return to work.
      RESULTS: Thirteen trials were located, evaluating the following interventions:
      manipulation, back school, exercise, advice, transcutaneous electrical nerve
      stimulation (TENS), hydrotherapy, massage, corset, cognitive behavioural
      treatment and co-ordination of primary health care. Most studies were of low
      quality and did not show a statistically significant effect of intervention. For
      the strict duration of low back pain (six weeks to three months), no evidence of
      high internal validity was found but when other methodological criteria were
      considered, evidence was found for the efficacy of advice. Furthermore, there is
      evidence that when a broader view is taken of the duration of subacute low back
      pain (seven days to six months), other treatments (e.g. manipulation, exercise,
      TENS) may be effective. CONCLUSIONS: Our review identified a major gap in the
      evidence for interventions that are currently recommended in clinical practice
      guidelines for the treatment of subacute low back pain. Lack of a uniform
      definition of subacute low back pain further limited current evidence.

PMID- 12501943
TI  - The effects of patellar taping on pain and neuromuscular performance in subjects
      with patellofemoral pain syndrome.
AB  - OBJECTIVE: To examine the immediate effects of patellar taping on pain and
      relative activity of vastus medialis obliquus to vastus lateralis in subjects
      with patellofemoral pain and patellofemoral joint malalignment. DESIGN: Pre- and
      post-treatment design, with order of testing determined randomly. SETTING:
      Outpatient physiotherapy department. SUBJECTS: Fifteen subjects with
      patellofemoral joint pain and malalignment. INTERVENTIONS: With and without
      patellar taping with a standard force of application. MAIN OUTCOME MEASURES: Pain
      and surface EMG activity ratio of vastus medialis obliquus to vastus lateralis
      during single-legged semi-squat with 20% of extra body weight loading. RESULTS:
      There was a significant decrease in anterior knee pain (p < 0.001) and vastus
      medialis obliquus to vastus lateralis activity ratio (p = 0.05) during single
      legged standing after patellar taping. CONCLUSIONS: Patellar taping can reduce
      pain in people with patellofemoral pain syndrome and patellofemoral malalignment
      but it decreases the relative activity of vastus medialis obliquus to vastus
      lateralis. Such a decrease in relative activity of vastus medialis obliquus after
      taping implies that it may not be suitable to combine patellar taping with vastus
      medialis obliquus facilitative exercise training.

PMID- 12501944
TI  - Use of cognitive-behavioural arthritis education programmes in newly diagnosed
      rheumatoid arthritis.
AB  - OBJECTIVE: To identify the effect of attending a cognitive-behavioural arthritis
      education programme on the health status of participants with newly diagnosed
      rheumatoid arthritis (RA) compared with a control group. DESIGN: Randomized
      controlled trial. SETTING: Hospital based. SUBJECTS: Newly diagnosed with RA.
      INTERVENTION: Participation in either a cognitive-behavioural arthritis education
      programme or a standard arthritis education programme (control group). Sessions
      for both groups lasted for 2 hours per week for four weeks. Subjects were
      examined at home by an assessor blinded to group allocation, prior to and three
      and six months following attendance. OUTCOME MEASURES: The main outcome measure
      was the Physical Function subscale of the Arthritis Impact Measurement Scale Two.
      Other outcome measures included erythrocyte sedimentation rate (ESR), joint count
      scores, assessments of pain and psychological status. RESULTS: Fifty-four
      subjects (mean time since diagnosis 4.5 months) took part. Baseline analysis
      revealed that the control group had significantly better levels of functional
      ability (U = 185; p = 0.009) and lower levels of helplessness (U = 168; p =
      0.002) prior to intervention. This difference remained unchanged three months
      later. Six months following the intervention no significant differences were
      noted between the groups for any measure of health status. There were no
      significant changes in health status over time in either group. CONCLUSION:
      Attending a cognitive-behavioural arthritis education programme had no
      significant effect on the health status of individuals newly diagnosed with RA.
      The move to early use of these programmes should be examined further, with a
      larger sample size and longer duration of follow-up.

PMID- 12501945
TI  - Deciding whether a change in a patient's performance is a genuine change.
AB  - Our purpose is to help clinicians decide whether a measured change in a patient's
      performance, usually in the direction of improvement, is likely to represent a
      true change. We set out the calculations to derive a minimal statistically
      significant change in certain measures commonly used in evaluating the outcome of
      rehabilitation. Many of these test measurements, e.g. walking time, are likely to
      show increased variability within patients as the mean level of performance
      increases in magnitude. We pay particular attention to the calculations in this
      case as the data should be transformed to remove the relationship by taking their
      natural logarithm. Confidence interval calculations for single measurements and
      for differences between two measurements (using the repeatability coefficient)
      are given both for data that show and for data that do not show a relation
      between variation and level of performance.

PMID- 12501946
TI  - The Standardized Three-metre Walking Test for elderly people (WALK3m):
      repeatability and real change.
AB  - OBJECTIVES: (i) To examine the relative and absolute retest within-session
      reliability of the Standardized Three-metre Walking Test for elderly people
      (WALK3m), using walking time and number of steps as measures. (ii) To give
      clinicians details of how they can use the minimal detectable change in order to
      decide whether a patient's WALK3m performance has really changed. (iii) To give
      rules to decide whether one trial rather than three is sufficient. DESIGN AND
      ANALYSIS: Subjects made three trials of WALK3m in the same session. Variability
      and level of performance were related so the data were log (ln) transformed.
      Relative reliability was measured by the intraclass correlation coefficient (ICC)
      then absolute reliability by the repeatability factor (RF) and minimal detectable
      change (MDC) (one-tailed and two-tailed) was derived from the within-subjects
      standard deviation. SETTING: Rehabilitation areas in the acute geriatric medical
      units at three south-west London hospitals. SUBJECTS: The standardizing sample
      consisted of 81 inpatients approaching discharge to their own homes. RESULTS: The
      ICC for walking time was 0.97 and for step counts 0.96. The MDC for walking is a
      36% decrease between first and second measurements. The corresponding value for
      step counts is 21%. CONCLUSION: WALK3m, whether measured by time or by step
      counts has excellent repeatability. Knowing the minimal detectable change can be
      of great value to clinicians who can calculate whether their patient is really
      making progress.

PMID- 12501947
TI  - Evaluation of cervical range of motion and isometric neck muscle strength:
      reliability and validity.
AB  - OBJECTIVE: To examine the test-retest reliability and construct validity of
      cervical active range of motion and isometric neck muscle strength as measured by
      the Multi Cervical Rehabilitation Unit (Hanoun Medical Inc., Ontario). DESIGN: A
      cross-sectional study. SETTING: Institutional practice. SUBJECTS: Twenty-one
      patients with neck pain and 25 healthy volunteers. METHODS: After a trial-run
      session, active range of motion (AROM) was measured in the subsequent two
      sessions, with 2-3 days in between. During each session, three measurements were
      taken for each direction (flexion, extension, lateral flexions and rotations).
      The measurement of isometric strength was after a 15-minute break following
      completion of the measurement of AROM. Three measurements were made for each of
      the six directions (flexion, extension, lateral flexions, protraction and
      retraction). The software of the Multi Cervical Rehabilitation Unit automatically
      recorded and calculated the maximum AROM and isometric strength. RESULTS: There
      was a good to high level of reliability in the measurement of AROM for both
      groups of subjects, with intraclass correlation coefficients (ICCs) ranging from
      0.81 to 0.96. Results also demonstrated very good to excellent reliability in
      isometric strength measurement (ICCs ranged from 0.92 to 0.99). Moreover, there
      was a significant difference in isometric neck muscle strength (p = 0.001) and in
      AROM (p = 0.034) between the two groups. CONCLUSIONS: The Multi Cervical
      Rehabilitation Unit was found to be reliable and valid for testing the cervical
      active range of motion and isometric neck muscle strength for both normal and
      patient subjects.

PMID- 12501948
TI  - Setting priorities for a discharge plan for stroke patients entering nursing home
      care.
AB  - OBJECTIVE: To agree priorities for the structure and content of the discharge
      process for stroke patients entering nursing home care. DESIGN: A formal priority
      setting exercise using the Nominal Group Technique. PARTICIPANTS: A panel of 12
      members of a multidisciplinary team from a hospital and community setting with
      experience in the management of stroke patients on a daily basis. RESULTS:
      Agreement was good and improved during the process (Kendall coefficient of
      concordance 'W increased from 0.48 to 0.58 for physical care needs, 0.45 to 0.75
      for care needs and 0.56 to 0.72 for the discharge process). The priorities for
      discharge were: 1) Plans need to be co-ordinated by one person 2) Clear written
      information on medication should be provided 3) Clear written information on
      nutritional needs should be provided. CONCLUSION: Agreement was reached by a
      panel of clinicians on an evidence-based discharge plan for stroke patients
      entering nursing home care.

PMID- 12501949
TI  - Goal attainment scaling in evaluating a multidisciplinary pain management
      programme.
AB  - OBJECTIVE: To examine the value of Goal Attainment Scaling (GAS) as a therapeutic
      tool and an outcome measure in a rehabilitation programme in the management of
      chronic pain. DESIGN: A prospective observational study. SETTING: A 15-day pain
      management programme, day case or residential, in an NHS Regional rehabilitation
      centre. SUBJECTS: One hundred and forty-nine consecutive patients enrolled during
      a 15-month period. INTERVENTIONS: Multidisciplinary structured educational
      programme of physiotherapy, occupational therapy and clinical psychology. MAIN
      OUTCOME MEASURES: GAS; timed tests of physical mobility measures; McGill Pain
      Questionnaire (MPQ); Pain Intensity Numerical Rating Scale (NRS); Oswestry low
      back pain Disability Questionnaire (ODQ); General Health Questionnaire (GHQ);
      Pain and Impairment Relationship Scale (PAIRS). GAS and physiotherapy measures
      were compared with baseline data at enrollment and at discharge 15 days later. At
      six-month follow-up all measures were repeated. RESULTS: Significant improvements
      at discharge were found for GAS, and physiotherapy measures. One hundred and
      twelve patients returned for review at six months, when improvements were
      maintained for GAS, sit/stand, Pain, ODQ and GHQ. GAS was shown to be a valid
      measure of ability, correlating significantly with walking improvement and
      somewhat less with a therapist-defined measure, suggesting some ability to
      discriminate. CONCLUSIONS: The improvement measured by GAS showed that patients
      were enabled by the programme to achieve personally valued goals over a six-month
      period and to improve on these more than on other more conventional outcome
      measures.

PMID- 12501950
TI  - Electrically induced and voluntary activation of physiologic muscle pump: a
      comparison between spinal cord-injured and able-bodied individuals.
AB  - OBJECTIVE: To evaluate the central haemodynamic responses during position changes
      from supine to sitting and during 30 min of standing between able-bodied and
      spinal cord-injured subjects. Also to assess the effects of the physiologic
      muscle pump in both groups during 30 min of standing. DESIGN: A repeated measure
      design. Both groups were tested on two different days under two conditions of 30
      min of stationary standing and 30 min of dynamic standing (voluntary activation
      of the lower leg muscles in able-bodied and FES-induced activation of these
      muscles in spinal cord injured). The order of testing was random. SETTING:
      Rehabilitation hospital. SUBJECTS: Fifteen healthy able-bodied and 14 healthy
      spinal cord-injured subjects. MAIN OUTCOME MEASURED: Stroke volume, cardiac
      output, heart rate, systolic blood pressure, diastolic blood pressure, mean
      arterial pressure and total peripheral resistance during supine-pre sitting,
      sitting-pre standing and during 30 min of standing. RESULTS: Significant
      reductions (p < 0.05) in systolic blood pressure, diastolic blood pressure and
      mean arterial pressure were found when spinal cord-injured subjects moved from
      sitting to standing during stationary standing; these values were maintained
      during dynamic standing. These values were maintained during both standing
      sessions in able-bodied subjects. During 30 min of stationary standing, there
      were significant reductions in stroke volume, cardiac output in both able-bodied
      and spinal cord-injured while their total peripheral resistance increased (p <
      0.05). During 30 min of dynamic standing, both groups maintained their
      haemodynamics at pre-standing values with the exception of significant reduction
      in stroke volume at 30 min of standing. CONCLUSION: FES-induced activation of the
      physiologic muscle pump during change in position from sitting to standing
      prevented orthostatic hypotension in spinal cord-injured subjects. During
      standing it had equal or even greater effect on improving blood circulation when
      compared with voluntary activation in able-bodied subjects. The use of FES during
      standing and tilting in spinal cord-injured individuals may prevent orthostatic
      hypotension and circulatory hypokinesis and improve tolerance to tilting and
      standing.

PMID- 12501951
TI  - Prediction of outcome of physiotherapy in advanced Parkinson's disease.
AB  - OBJECTIVE: Prediction of the effect of a home physiotherapy intervention on the
      basis of four clinical characteristics of patients with advanced Parkinson's
      disease. DESIGN: A repeated measures design comparing six weeks without treatment
      with six weeks of physiotherapy and a follow-up of 12 weeks. SUBJECTS: Persons
      with Parkinson's disease without dementia and suffering from considerable
      functional disability. INTERVENTION: Community physiotherapists treated patients
      in the home situation three times a week teaching cueing and conscious movement
      control for walking and carrying out transfers in and out of beds and chairs.
      MAIN OUTCOME MEASURES: Mental status, disease severity, age and mood were
      included as predictor variables. A new functional scale developed as part of a
      previous study was used as the dependent variable administered in both the
      hospital and the home to determine whether the outcome generalized from the
      learning to a different environment. RESULTS: Only disease severity was a
      negative predictor of treatment outcome at home. In the hospital setting none of
      the factors predicted the immediate effect of treatment but cognitive ability and
      age were determinants of whether the treatment effects were maintained in the
      long term. CONCLUSIONS: Using cueing and cognitive strategies benefited younger
      and older patients with Parkinson's disease alike. However, the findings indicate
      targeting of treatment at patients with milder disease severity and providing
      follow-up treatment for older and cognitively less able patients.

PMID- 12501952
TI  - Do static or dynamic AFOs improve balance?
AB  - OBJECTIVE: To verify if partial or total limitation of degrees of freedom at
      ankle joints could help patients with balance disorders in standing and walking.
      DESIGN: A cross-over design was chosen. Patients with multiple sclerosis (MS)
      were tested in three experimental conditions: barefooted, wearing ankle foot
      orthoses (AFOs), and wearing AFOs that allowed plantar flexion. SETTING:
      Neurorehabilitation unit in a rehabilitation centre. SUBJECTS: Fourteen patients
      suffering from MS with mild strength problems and balance disorders that required
      them to use walking aids outside. MAIN OUTCOME MEASURES: Tests inferring static
      and dynamic skills were carried out in the three experimental conditions
      described above. RESULTS: Improvements were obtained in static balance tests
      especially wearing dynamic AFOs; the number of patients who were able to pass
      tasks on balance in upright position such as 'standing with feet together, head
      extended' increased from three to nine. Dynamic balance was impaired especially
      with static AFOs; the time spent walking 10 metres with these orthoses increased
      by 172% with respect to barefoot; less difference (113%) has been reported
      wearing dynamic AFOs. CONCLUSION: Static and dynamic AFOs improved static
      balance, while dynamic balance was impaired especially by static AFOs; less
      negative influence on dynamic balance has been found while wearing dynamic AFOs.

PMID- 12501953
TI  - Reliability and validity of the Cantonese version of the Test of Everyday
      Attention among normal Hong Kong Chinese: a preliminary report.
AB  - OBJECTIVE: To validate the translated Cantonese version of an ecologically valid
      clinical test of attention - the Test of Everyday Attention (TEA). DESIGN: A
      cross-sectional study was conducted on a sample of 49 healthy participants with a
      mean age of 25.9 years in the Hong Kong Chinese setting. OUTCOME MEASURES: These
      included the Color Trails Test, Stroop Colour-Word Test, Symbol Digit Modalities
      Test, Word Fluency Test, Design Fluency Test, Digits Backward Span Test and
      Modified Six Elements Test. In addition, the Cognitive Failures Questionnaire and
      Dysexecutive Questionnaires were also administered to the participants. RESULTS:
      The TEA was found to have a good range of test-retest reliability. The convergent
      validity of the instrument was established by correlation of the TEA with various
      measurements of attention, whereas the divergent validity was demonstrated by the
      insignificant correlation with tests of other cognitive functioning. Factor
      analysis of the TEA subtests replicated the major factor structure of the
      original version. CONCLUSION: The present study indicates that the translated TEA
      represents a culturally appropriate tool for measuring everyday life attention
      performance among the healthy Hong Kong Chinese.

PMID- 12501954
TI  - Outreach services in spinal injury rehabilitation.

PMID- 12501955
TI  - UK bovine carcass meat consumed as burgers, sausages and other meat products: by
      birth cohort and gender.
AB  - BACKGROUND: The most likely human exposure to bovine spongiform encephalopathy
      (BSE) is dietary, through beef mechanically recovered meat (MRM) and head meat
      used in burgers, sausages and other meat products. The majority, reportedly 90%
      of beef MRM and 80% of head meat, was used in burgers. To enable quantification
      of UK dietary exposure to BSE, we quantified bovine carcass meat consumed as
      burgers, sausages and other meat products by birth cohort, gender and calendar
      period (1980-1989, 1990-1996). METHODS: Synthesis of dietary data (cross
      sectional National Dietary and Nutrition Surveys, and serial National Food
      Surveys and Realeat Surveys) to simulate weekly consumption by one-thousandth of
      the UK population in each year from 1980 to 1996. FINDINGS: In 1980-1989, the
      highest number of consumers (per 7 days) of all three food groups was in the 1940
      1969 birth cohort - averaging 3.7 million male consumers of burgers, 2.6 million
      of sausages and 8.5 million of other meat products. The post-1969 birth cohort
      had the next highest number of consumers of burgers (1.8 million males). In 1990
      1996, consumer numbers declined for the two older cohorts, most strikingly for
      burgers (down to 2.5 million males in the 1940-1969 cohort). The 1940-1969 cohort
      retained the highest number of consumers of sausages and other meat products, and
      second place for burgers. Male consumption was higher, even in the pre-1940 birth
      cohort where, for demographic reasons, female consumers outnumbered males. In the
      post-1969 birth cohort, female consumption of bovine carcass meat weight as
      burgers increased from 68 tonnes in 1980-1989 to 81 tonnes in 1990-1996, and male
      consumption increased more markedly (by 41%) from 84 tonnes to 119 tonnes; and
      similarly for other meat products. INTERPRETATION: Properly marshalled age-group
      and gender-specific consumption data contribute to a clearer understanding of the
      demography of those who were at risk of dietary exposure to BSE and of when their
      exposure intensity was greatest. Other countries may need to consider using
      dietary data to model their human BSE exposure from UK and other BSE-affected
      regions.

PMID- 12501956
TI  - UK dietary exposure to BSE in beef mechanically recovered meat: by birth cohort
      and gender.
AB  - BACKGROUND: Meat recovered mechanically from bovine vertebral columns for use in
      burgers, sausages and other meat products may have been contaminated with bovine
      spongiform encephalopathy (BSE) from recovered spinal cord and dorsal root
      ganglia (DRG). We quantified UK exposure to BSE in beef mechanically recovered
      meat (MRM) by birth cohort (born pre-1940, in 1940-1969, post-1969), gender and
      calendar period (1980-1989, 1990-1996) because information on any two of BSE
      exposure intensity, vCJD incubation period and the new cases of vCJD tells us
      about the third. METHODS: Synthesis of evidence on BSE epidemiology, MRM
      production, infectivity in spinal cord and DRG, and UK dietary consumption.
      FINDINGS: Production of beef MRM peaked at 5000 tonnes in 1987, was nil in 1989
      but recovered to 2000 tonnes in 1995 when it ceased altogether; reportedly 90%
      was used in burgers. Mean weight of spinal cord recovered per carcass was 3.3 g
      (95% credible interval 0.24-12.02 g) before the specified bovine offal (SBO)
      legislation and 1.5 g (0.02-8.30 g) after the legislation; whereas recovered
      weight of DRG (as infectious as spinal cord) was 27 g. Recovery of spinal cord
      from 1-year pre-clinical bovines peaked in 1988 at 238 g and of DRG in 1993 at
      4250 g (medians). Median infectivity (5th and 95th percentiles) consumed in beef
      MRM was 33 250 (30 550-35 950), 65 600 (60 250-71 050) and 14 350 (13 150-15 600)
      bovine oral (Bo) ID50 units for the post-1969, 1940-1969 and pre-1940 birth
      cohorts in 1980-1989; and 44 250 (41 300-47 350), 39 600 (37 100-42,400) and 8750
      (8100-9350) Bo ID50 units in 1990-1996. Males consumed almost 58% of infectivity
      in both periods. If the worst-case level of infectivity pertained, exposure,
      instead of halving in 1990-1996, would be sustained at around its 1980-1989 level
      for the two older birth cohorts and would have doubled in 1990-1996 for the post
      1969 birth cohort. INTERPRETATION: SBO legislation in 1989 contributed only a 6%
      reduction in the infectivity in beef MRM. Salient sensitivity issues are
      highlighted.

PMID- 12501957
TI  - UK dietary exposure to BSE in head meat: by birth cohort and gender.
AB  - BACKGROUND: UK dietary exposure in 1980-1996 to the bovine spongiform
      encephalopathy (BSE) infectious agent through the consumption of beef
      mechanically recovered meat (MRM) contained in burgers, sausages and other meat
      products has already been quantified by birth cohort (born pre-1940, 1940-1969 or
      post-1969) and gender. In this paper, similar quantification is undertaken for
      the consumption of bovine head meat. METHODS: Synthesis of evidence on clinical
      BSE bovines, on bovines slaughtered in the last year of their BSE incubation
      period, brain contamination during head meat production, brain infectivity
      (option 1: 1-year preclinical bovine 54% as infectious as clinical BSE bovine;
      option 2: 1-year pre-clinical bovine as infectious as clinical BSE bovine) and
      1980-1996 UK dietary consumption of head meat in burgers, sausages and other meat
      products. FINDINGS: Median infectivity consumed in head meat was 49 900 (67 800
      for infectivity option 2), 96 200 (126 900) and 24950 (32 800) bovine oral (Bo)
      ID 50 units for the post-1969, 1940-1969 and pre-1940 birth cohorts in 1980-1989;
      and 143 950 (266 550 for infectivity option 2), 150 900 (279 500) and 38 350 (71
      250) Bo ID50 units in 1990-1996. Males consumed almost 58% of infectivity in 1980
      1996. For all three birth cohorts, exposure to BSE in head meat was higher in
      1990-96 for both infectivity options. Median infectivity consumed in head meat
      and beef MRM was 83 150 (109 000 for infectivity option 2), 161 900 (207 450) and
      39 300 (50 450) Bo ID50 units for the post-1969, 1940-1969 and pre-1940 birth
      cohorts in 1980-1989; and 188 200 (348 700), 190 600 (353 050) and 47 200 (87
      550) Bo ID50 units in 1990-1996. INTERPRETATION: Males consumed almost 58% of BSE
      infectivity in head meat and beef MRM, which is consistent with 60 males of 113
      variant Creutzfeldt-Jakeb disease (vCJD) onsets to 30 November 2001. If vCJD
      onsets to that date had all been infected in 1980-1989, 65 of 113 vCJD onsets in
      the post-1969 cohort are not consistent with its BSE exposure in 1980-1989 unless
      the vCJD incubation period or susceptibility depends on age, or another exposure
      is involved. Experimental data are needed to identify which brain material
      contaminates head meat, and further pathogenesis data are needed to determine the
      corresponding infectivity. Other salient sensitivity issues are highlighted.

PMID- 12501958
TI  - Measurement of passive smoking in adults: self-reported questionnaire or serum
      cotinine?
AB  - BACKGROUND: Low to moderate agreement between self-reported exposure to
      environmental tobacco smoke (ETS) and serum cotinine levels in non-smokers
      questions the accuracy of the measurement of ETS exposure. We examined the
      relationship of serum cotinine to different self-reported ETS questionnaires in a
      large community-based study. METHODS: Subjects were derived from four Scottish
      MONICA surveys. Agreement between self-reported ETS (yes/no) and serum cotinine
      levels (> 0, 0) in non-smokers was tested by K, and the difference in cotinine
      levels among self-reported ETS exposure by ANOVA and the relationship by linear
      regression. RESULTS: None of the values for K was > 0.24 for any ETS
      questionnaire. In non-smokers with serum cotinine > 0, cotinine levels increased
      with increasing ETS exposures. In the first and second surveys with the
      questionnaire of ETS exposure in the last 3 days, standardised coefficients were
      0.28-0.39, while in the third and fourth surveys with the questionnaire of a
      total exposure to ETS at work, at home and in other places the standardised
      coefficients were 0.19-0.36, with the questionnaire of ETS daily exposure hours,
      0.23-0.36. The relationship between self-reported ETS and cotinine levels varied
      with the questionnaires, and with the time of day of the blood sample collection.
      In current smokers, cotinine levels were significantly related to both the number
      of cigarettes smoked daily (the coefficients were 0.13-0.41) and time elapsed
      since the last cigarette (-0.24 to -0.40). CONCLUSION: The findings raise the
      question of whether it is ideal to take only serum cotinine as an index of ETS
      exposure in adults, because of time delays between ETS exposure and blood
      collection, and suggest the combined use of appropriately worded self-reported
      questionnaires and cotinine levels to estimate ETS exposure.

PMID- 12501959
TI  - Transmission/disequilibrium test when neither parent is available in some
      families: a non-iterative approach.
AB  - BACKGROUND: The transmission/disequilibrium test (TDT) is a simple method of
      detecting linkage between a marker locus and a disease-susceptibility locus. The
      test requires genotype data from the affected individuals (the probands) and
      their parents, the 'case-parents triads'. However, missing data from parents
      often complicate the situations. Several non-iterative methods, such as the
      sibling-based TDT, the reconstruction-combined TDT, and the 1-TDT have been
      proposed to deal with the problem. But when the father, the mother, and other non
      proband siblings in a family are all unavailable for study, that family has to be
      excluded from analysis by any of the above methods. METHODS: The author proposes
      a new non-iterative method to deal with the situation when the data contain some
      'orphaned' probands. The method utilises the complete data from case-parents
      triads to infer probabilistically the missing parental genotypes, under the
      assumption that the missingness is independent of genotype and ethnic origin. The
      methods can be tailored to specific genetic models, such as the gene-dose,
      dominance, and recessive alternatives. RESULTS: Simulation analysis shows that,
      under the null hypothesis of no linkage, the proposed method is not prone to
      produce an excess of false positive results, even in complex situations such as
      population stratification or assortive mating. Under the linkage alternative, the
      new method recaptures much of the information that would be lost by discarding
      the orphaned probands. DISCUSSION: The method provides a way for dealing with the
      situation where neither parents nor siblings are available in a TDT study.

PMID- 12501960
TI  - Ling's death: an ethnography of a Chinese woman's suicide.
AB  - Over the past decade, great concern has been expressed about the high suicide
      rates in China, especially among women and young women in particular. However,
      most of the information that has been presented has considered macro-level data
      and speculated on why women are so vulnerable to self-harm. This article presents
      the detailed story of one village woman who killed herself and suggests that
      motives and behavior are more complex than the cultural script and statistics
      suggest. Although depression is said to be commonly present in people who kill
      themselves in Western countries, this may not be the case in China.

PMID- 12501961
TI  - Attempted suicide among young rural women in the People's Republic of China:
      possibilities for prevention.
AB  - This article reports on a sample of 147 women under age 35 living in rural areas
      in China who had attempted suicide and were treated in the emergency room of
      hospitals in four different locations. The interview instrument took 2 to 3 hours
      to complete and included audiotaped in-depth interviews with the patient and
      family members (separately); detailed evaluation of the circumstances surrounding
      the attempt, life events, and the family environment; and a formal psychiatric
      evaluation by an attending-level psychiatrist. Overwhelmingly, the method used by
      the attempters was poisoning with highly lethal pesticides and organic
      fertilizers. The women's suicidal behavior was characterized by high levels of
      impulsivity; little effort to seclude themselves before and after ingesting
      poison; and low rates of mental illness, including depression. Detailed
      suggestions are made about ways to implement suicide prevention strategies within
      the particular social and economic context of China.

PMID- 12501962
TI  - Studying suicide with psychological autopsy: social and cultural feasibilities of
      the methodology in China.
AB  - As China opens its door to the world, suicide research is making rapid progress
      using methods and instruments developed in the West. This is a feasibility study
      of the psychological autopsy methodology applied in China, with its emphasis on
      the social and cultural environments. With samples of 66 completed suicides and
      66 community normal living controls, the authors found that it is feasible to
      interview at least two informants for each suicide case and each control, between
      2 and 6 months after the suicide. With the Chinese-cultivated contacting method
      of recruiting cases, the refusal rate is nearly zero. The Western-developed
      methodology per se proved to be valid in the Chinese culture. Ethical
      considerations in the context of Chinese culture are as important as in the West.
      Psychological autopsy technique is shown to be an equally applicable method for
      the study of completed suicides in Chinese culture as it is in the West. Future
      epidemiological research on Chinese suicide should use the psychological autopsy
      method to collect data from larger samples in order to increase our understanding
      of the risk factors for Chinese suicides.

PMID- 12501963
TI  - Why people engage in parasuicide: a cross-cultural study of intentions.
AB  - Information obtained at interview from 1,646 parasuicide patients in 14 regions
      in 13 European countries participating in the WHO/EURO Multicentre Study on
      Suicidal Behaviour was used to study self-reported intentions involved in
      parasuicide. Comparisons were made across cultures, genders, and age groups.
      Although some statistically significant differences were found, the effect sizes
      were very small. The main finding from this study is thus that parasuicide
      patients in different countries tend to indicate that similar types of intentions
      are involved in their acts of parasuicide, and that the intentions do not vary
      greatly with gender or age. The hypothesis that rates of suicide and parasuicide
      vary between regions with the frequency with which suicidal intention is
      indicated by the patients was also tested, but was supported only for women and
      in relation to national suicide rates. The findings from this study are likely to
      be generalizable to other settings and have implications for clinical practice.

PMID- 12501964
TI  - Mental health literacy of those with major depression and suicidal ideation: an
      impediment to help seeking.
AB  - Mental health literacy is the knowledge and beliefs about mental disorders that
      aid their recognition, management, or prevention, and is an important determinant
      of help seeking. This has relevance in suicide prevention, particularly for those
      with major depression, the clinical condition most frequently associated with
      suicidal behavior. In this study of a random and representative community sample,
      a vignette depicting classical features of major depression was presented to
      subjects along with questions related to mental health literacy. The responses of
      those with major depression, as delineated by the Primary Care Evaluation of
      Mental Disorders instrument, both with and without suicidal ideation, were
      compared to those of a third group of respondents. The results demonstrated that
      despite increased professional contact by those with major depression and
      suicidal ideation, there were few differences among the three groups on either
      open-ended or direct questions related to mental health literacy. This indicates
      that increased professional contact in itself was not related to increased mental
      health literacy, and suggests that more specific psychoeducational programs are
      required.

PMID- 12501965
TI  - Religiosity, attributional style, and social support as psychosocial buffers for
      African American and white adolescents' perceived risk for suicide.
AB  - Psychosocial buffers were evaluated for their relative contributions to
      adolescents' perceived risk for suicide. A community sample of African American
      and White adolescents (N = 1,098) rated the likelihood that they would die by
      suicide and completed standardized measures of depression, hopelessness,
      intrinsic and extrinsic religiosity, orthodoxy, social support, and causal
      attributional style. Orthodoxy-commitment to core beliefs-emerged as the single
      strongest correlate after controlling for the effects of other buffers. The
      effect of depression on perceived suicide risk was moderated by the adolescent's
      degree of orthodoxy. Commitment to core, life-saving beliefs may help explain the
      religion-suicide link for adolescents.

PMID- 12501966
TI  - The association between homelessness and suicidal ideation and behaviors: results
      of a cross-sectional survey.
AB  - This study was carried out with three goals: (1) to determine the prevalence of
      suicidal ideation and suicide attempts among the homeless; (2) to determine what
      aspects of homelessness predict suicidality, and (3) to determine which aspects
      remain predictive after controlling for key covariates, such as mental illness. A
      sample of 330 homeless adults were interviewed. Sixty-one percent of the study
      sample reported suicidal ideation and 34% had attempted suicide. Fifty-six
      percent of the men and 78% of the women reported prior suicidal ideation, while
      28 percent of the men and 57% of the women had attempted suicide. Childhood
      homelessness of at least 1 week without family members and periods of
      homelessness longer than 6 months were found to be associated with suicidal
      ideation. Psychiatric diagnoses were also associated with suicidality in this
      sample.

PMID- 12501967
TI  - Does writing about suicidal thoughts and feelings reduce them?
AB  - To assess whether writing with cognitive change or exposure instructions reduces
      depression or suicidality, 121 undergraduates screened for suicidality wrote for
      20 minutes on 4 days over 2 weeks. They were randomly assigned to reinterpret or
      to write and rewrite traumatic events/emotions, or to write about innocuous
      topics. The three groups (N = 98) who completed pre-, post-, and 6-week follow-up
      were not different on suicidality or depression. All subjects reported fewer
      automatic negative thoughts over the 2 weeks; they also reported higher self
      regard but more health center visits at follow-up. Suicidal thoughts may be more
      resistant than physical health to writing interventions.

PMID- 12501968
TI  - Simon Muralis: self-sequestration and psychotherapeutic failure.

PMID- 12501969
TI  - Immediate post intervention effects of two brief youth suicide prevention
      interventions.

PMID- 12501970
TI  - Suicide and firearm prevalence.

PMID- 12501971
TI  - Composite somatotroph--ACTH-immunoreactive pituitary adenoma with transformation
      of hyperplasia to adenoma.
AB  - The majority of pituitary adenomas are solitary and monohormonal, producing only
      one hormone. Double or multiple adenomas are rare. Plurihormonal adenomas may be
      monomorphous consisting of one cell type producing more than one hormones or
      plurimorphous composed of two or more distinct cell populations each producing
      different hormones. Primary pituitary hyperplasia is uncommon and transformation
      to adenoma has rarely been documented. We describe a unique case of somatotroph
      adenoma combined with ACTH-immunoreactive cell hyperplasia and focal
      transformation to adenoma. The 53-yr-old man was presented with a 2-yr history of
      headaches, enlargement of the hands and feet and coarsening of facial features.
      His blood GH was 17.5 ng/ml and he had absence of GH suppressional oral glucose
      tolerance testing. MRI demonstrated a mass with maximum diameter of 1.5 cm, on
      the left side of the pituitary, without invasion of surrounding tissues.
      Transsphenoidal surgery was performed. Morphology disclosed a mostly chromophobic
      tumor, immunoreactive for GH with ultrastructural characteristics of sparsely
      granulated somatotroph adenoma. The adenoma cell population was focally admixed
      with hyperplastic PAS positive and ACTH immunoreactive cells showing the electron
      microscopic features characteristic of corticotrophs. In these areas the acini
      were enlarged with distorted architecture of the reticulin pattern. Dissolution
      of the reticulin fiber network and transformation of hyperplastic ACTH
      immunoreactive cells to adenoma was evident in small areas. The hyperplastic and
      adenomatous ACTH-immunoreactive cells were admixed with somatotroph adenoma
      cells. Due to lack of biochemically obvious cortisol hypersecretion, this ACTH
      immunoreactive adenoma was classified as silent "corticotroph" subtype 1. This is
      an unusual case of composite pituitary adenoma consisting of somatotroph cells
      and hyperplastic ACTH-immunoreactive cells transforming to a frank adenoma.

PMID- 12501972
TI  - Gamma knife radiosurgery in the management of patients with acromegaly: a review.
AB  - Although acromegaly is a rare disease, the need for an effective treatment that
      is able to induce biochemical cure is an extremely important issue.
      Unsuccessfully treated acromegaly is associated with increased morbidity and an
      age-corrected mortality so that early and aggressive therapy to normalize
      hormonal levels should be instituted at diagnosis. Ideally, the growth hormone
      secreting adenoma should be completely resected, with preservation or subsequent
      restoration of pituitary function. Patients with recurrence or failure after
      surgery are treated with a second surgery, medical, radiation treatment, or
      combined modality treatment. Steotactic radiosurgery with gamma knife allows the
      delivery of focused radiation in a single session to the pituitary tumor that
      delivers a more biologically effective dose to the tumor than fractionated
      radiotherapy. Its use as a primary or adjuvant treatment for acromegalics may be
      more cost effective than medical treatment in these patients. Although it seems
      to be very effective in controlling growth and secretion of the growth hormone
      secreting pituitary adenomas, there is a chance that some major risks from gamma
      knife radiosurgery might occur. This article will review the role that gamma
      knife radiosurgery might have in patients with acromegaly.

PMID- 12501973
TI  - Dietary sodium modulates mRNA abundance of enzymes involved in pituitary
      processing of proopiomelanocortin.
AB  - The messenger RNA abundance of proopiome-lanocortin (POMC) is increased in
      neurointermediate lobe (NIL) of rat pituitary when ingesting a high sodium diet
      (8%; HSD), as is the plasma concentration of the natriuretic peptide gamma
      melanocyte stimulating hormone (gammay-MSH) derived from it. We examined whether
      the HSD also increases the mRNA abundance in rat NIL of proconvertases 1 and 2
      (PC1, PC2), enzymes involved in the processing of POMC into gamma-MSH. PC1 mRNA
      increased by 40% after two weeks of the HSD and by 84% after three weeks. PC2
      mRNA increased by 40% after two weeks and by more than 3 fold after three weeks.
      These results for PC2 were confined to NIL as shown by in situ hybridization at
      one and two weeks, and were accompanied by a significant increase in NIL PC2
      protein after three weeks of the HSD as measured by immunoblotting. The increases
      in PC1 and PC2 mRNA abundance were paralleled by an increase in POMC mRNA level
      in NIL. Plasma gamma-MSH immunoreactivity averaged 35.1 +/- 3.3 fmol/ml in rats
      on the LSD, but increased to 70.9 +/- 4.8 fmol/ml after 3 weeks of the HSD (p <
      0.002 vs LSD). These results confirm that the HSD increases the plasma
      concentration of gamma-MSH, consistent with a role for it as a circulating
      natriuretic peptide. The increased NIL expression of PC1 and PC2 in parallel with
      POMC in response to the HSD suggests that these changes are part of the
      coordinated response to states of sodium surfeit.

PMID- 12501974
TI  - Pathogenesis and prevalence of hypertension in acromegaly.
AB  - Hypertension is an important complication of acromegaly, contributing to the
      increased morbidity and mortality of this condition. Prevalence of hypertension
      in acromegalic patients is about 35%, ranging from 18 to 60% in different
      clinical series, and the incidence is higher than in the general population. The
      lowering of blood pressure observed concomitantly with the reduction in GH levels
      after successful therapy for acromegaly suggests a relationship between GH and/or
      IGF-I excess and hypertension. The exact mechanisms underlying the development of
      hypertension in acromegaly are still not clear but may include several factors
      depending on the chronic exposure to GH and/or IGF-I excess. Experimental and
      clinical studies suggest that the anti-natriuretic action of GH (due to direct
      renal action of GH or IGF-I and/or to indirect, systemic GH or IGF-I-mediated
      mechanisms) may play a role in the pathogenesis of hypertension. Acromegaly is
      frequently associated with insulin resistance and hyperinsulinaemia which may
      induce hypertension by stimulating renal sodium absorption and sympathetic
      nervous activity. Whether sympathetic tone is altered in acromegalic hypertensive
      patients remains a matter of debate. Recent studies indicate that an increased
      sympathetic tone and/or abnormalities in the circadian activity of sympathetic
      system could play an important role in development and/or maintenance of elevated
      blood pressure in acromegaly, and may partially account for the increased risk of
      cardiovascular complications. Acromegalic cardiomiopathy may also concur to
      elevate blood pressure and can be aggravated by the coexistence of hypertension.
      Finally, a role of GH and IGF-I as vascular growth factors cannot be excluded. In
      conclusion, acromegaly is associated with hypertension, but there is still no
      real consensus in the literature on the mechanisms behind the development of the
      high blood pressure.

PMID- 12501975
TI  - Cardiovascular complications in acromegaly: methods of assessment.
AB  - Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy,
      dilation and diastolic filling abnormalities has been widely reported in
      literature. Generally, ventricular hypertrophy is revealed by echocardiography
      but early data referred increased cardiac size by standard X-ray. Besides,
      echocardiography investigates cardiac function and value disease. There are new
      technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non
      invasive ultrasound tool which extends Doppler applications beyond the analysis
      of intra-cardiac flow velocities until the quantitative assessment of the
      regional myocardial left ventricular wall motion, measuring directly velocities
      and time intervals of myocardium. The radionuclide techniques permit to study
      better the cardiac performance. In fact, diastolic as well as systolic function
      can be assessed at rest and at peak exercise by equilibrium radionuclide
      angiography. This method has a main advantage of providing direct evaluation of
      ventricular function, being operator independent. Coronary artery disease has
      been poorly studied mainly because of the necessity to perform invasive
      procedures. Only a few cases have been reported with heart failure study by
      coronarography and having alterations of perfusion which ameliorated after
      somatostatin analog treatment. More recently, a few data have been presented
      using perfusional scintigraphy in acromegaly, even if coronary artery disease
      does not seem very frequent in acromegaly. Doppler analysis of carotid arteries
      can be also performed to investigate atherosclerosis: however, patients with
      active acromegaly have endothelial dysfunction more than clear-cut
      atherosclerotic plaques. In conclusion, careful assessments of cardiac function,
      morphology and activity need in patients with acromegaly.

PMID- 12501976
TI  - Prevalence and pathogenesis of sleep apnea and lung disease in acromegaly.
AB  - Respiratory disorders are common and important complications in acromegaly.
      Patients suffering from acromegaly display a 1.6-3.3 fold increase in mortality
      rate, which is due to respiratory disorders in 25% of cases. In these patients,
      mortality for lung disease is 2-3 fold higher than in the general population.
      Every portion of the respiratory system may be involved. Deformities of facial
      bones, edema and hypertrophy of the mucosae and pharyngeal and laryngeal
      cartilages, enlargement of the tongue and inspiratory collapse of the
      hypopharinx, all may contribute to respiratory alterations. Nasal polyps,
      "hormonal rhinitis", changes of the voice and snoring are common occurrences.
      Though rarely, a laryngocele may ensue. Pneumomegaly is frequently observed and,
      as suggested by functional studies, might be due to an increased number rather
      than volume of the alveoli. An obstructive respiratory syndrome caused by mucosal
      thickening of the upper airways and bronchi is observed in 25% of female and 70%
      of male patients. The sleep apnea syndrome (SAS) affects 60-70% of acromegalic
      patients. SAS may be of obstructive, central or mixed type. Obstructive SAS is
      the prevailing form in acromegaly. It is due to intermittent obstruction of upper
      airways with preserved activity of the respiratory center, as testified by the
      remarkable thoracic and abdominal respiratory efforts. The pathogenesis of the
      central type of SAS is more complex. Narrowing of the upper airways may induce
      reflex inhibition of the respiratory center. Moreover, increased GH levels and,
      possibly, defects in the somatostatinergic pathways, may increase the ventilatory
      response of the respiratory center to carbon dioxide, thereby leading to
      respiratory arrest. In the mixed type of SAS, the phenomena underlying the other
      two forms coexist. Oxygen desaturation concomitant with the apneic episodes
      accounts for the frequent nocturnal wakening and diurnal drowsiness. Among the
      clinical correlates of SAS, arterial hypertension is of particular interest due
      to the close correlation existing between the two disorders. Sleep deprivation
      related to SAS seems per se to favor the appearance of hypertension. Moreover,
      short lasting hypoxemia may induce prolonged elevations of blood pressure,
      mediated by decreased endothelial generation of nitric oxide. Thus, since
      cardiovascular events are the main cause of mortality in patients with
      acromegaly, it is reasonable to hypothesize that SAS is involved in the reduced
      life span of these patients.

PMID- 12501977
TI  - Acromegalic arthropathy.

PMID- 12501978
TI  - Pituitary macroadenoma secreting thyrotropin and growth hormone: remission of
      bihormonal hypersecretion in response to lanreotide therapy.
AB  - We report a case of mixed TSH- and GH-secreting pituitary adenoma in a 60-year
      old female patient. She presented with bitemporal hemianopsia and large invasive
      pituitary macroadenoma. Blood hormone levels determinations revealed elevated
      thyroid hormones, TSH, and IGF-1 with a relatively low GH. The patient had a mild
      acromegalic appearance but did not display signs of thyrotoxicosis or goiter. She
      underwent two pituitary surgical procedures followed by radiotherapy, but despite
      treatment was still hormonally active. Pathological examination of the resected
      tumor immunostained positively for both TSH and GH. The patient was subsequently
      treated with injections of lanreotide, a depot long-acting somatostatin analog,
      resulting in suppression of blood TSH, thyroid hormones, alpha-subunits, GH and
      IGF-1.

PMID- 12501979
TI  - Coexistence of thyrotropin-producing pituitary adenoma with papillary
      adenocarcinoma of the thyroid--a case report and surgical strategy.
AB  - We report a very rare case of thyrotropin (thyroxin stimulating hormone, TSH)
      producing pituitary adenoma coexisting with a papillary adenocarcinoma of the
      thyroid. A 45-year-old woman presented with hyperhidrosis and a nodule in the
      left thyroid that was first noticed one year earlier. An endocrinological
      examination showed elevated serum levels of free triiodothyronine (T3) and free
      throxin (T4) without inhibition of TSH, suggesting the presence of syndromes of
      inappropriate secretion of TSH. A specimen obtained by needle aspiration of the
      thyroid nodule revealed the presence of papillary adenocarcinoma. Magnetic
      resonance images demonstrated a pituitary macroadenoma. The patient was diagnosed
      as having a TSH-producing pituitary adenoma coexisting with a papillary
      adenocarcinoma of the thyroid. The patient underwent a total thyroidectomy with
      resection of the neighboring lymph nodes. Two weeks after this surgery, the
      pituitary adenoma was totally removed via a pterional approach. Histological and
      immunohistochemical examinations of the surgical specimens confirmed the lesion
      as a papillary adenocarcinoma of the thyroid and a TSH-producing pituitary
      adenoma. Serum TSH levels decreased to undetectable levels immediately after the
      surgery for the pituitary adenoma. Prolonged stimulation of the thyroid gland by
      TSH may be involved in the growth of thyroid carcinoma. In cases with a TSH
      producing pituitary adenoma, the possible coexistence of thyroid carcinoma should
      be carefully ruled out. In such cases, a total thyroidectomy followed by TSH
      level normalization should be performed. Incomplete removal of the thyroid might
      enable the carcinoma to re-grow if TSH level can not be normalized after the
      pituitary adenomectomy.

PMID- 12501980
TI  - Decreased insulin requirements after LAR-octreotide but not after lanreotide in
      an acromegalic patient.
AB  - A diabetic acromegalic man, not cured after surgery and radiosurgery, received
      lanreotide i.m. with great clinical and biochemical improvement. He required NPH
      insulin (76 to 84 units/day) to control his diabetes mellitus. Thirty-six hours
      after changing to LAR-octreotide (20 mg i.m/month) he presented symptomatic
      hypoglycemia, repeated at 48 and 72 h (50 mg/dL), despite reducing insulin to 26
      Units/day. Thereafter, he reduced insulin by 30 to 50% for the first week after
      each LAR-octreotide injection, and gradually increased it again over the next 3
      weeks. This situation persists after every injection 3 years later; this
      consistent behavior supports a specific effect of LAR-octreotide, and not a by
      chance phenomenon. No marked changes in circulating GH, IGF-1, immunoreative
      insulin, C-peptide, testosterone and glucose were observed prior to, and 3, 7,
      14, 21, and 28 days after LAR-octreotide; however, there was 28% fall in plasma
      glucagon after 7 days, which rose thereafter. C-peptide (< 1.8 ng/mL) was
      indicative of decreased beta-cell function. To our knowledge, this is the first
      report of such a distinct differential behaviour of blood glucose and insulin
      requirements with different somatostatin analogs, and is worth recalling when
      starting an insulin-treated diabetic patient on this treatment. It may be related
      to a preferential binding of LAR-octreotide to subtype 2 somatostatin receptors
      in the pancreas, while lanreotide preferentially binds to subtype 5, not
      expressed in this tissue; this would explain the fall in glucagon, in parallel to
      the decrease in insulin requirements after LAR-octreotide; however, a
      contribution of differences in the effect of both somatostatin analogues on
      postreceptor signalling systems and/or intestinal carbohydrate absorption cannot
      be entirely ruled out.

PMID- 12501981
TI  - Pituitary surgery complicated by haemorrhagic necrosis of residual tumour.
AB  - Haemorrhagic necrosis of residual pituitary tumour following partial excision has
      not previously been well described. This is differentiated from post-operative
      sellar haematoma due to inadequate haemostasis on the basis of absent free clot.
      The authors report two cases of large macroadenomas with significant supra-sellar
      extension which were complicated by haemorrhagic necrosis of residual tumour
      following initial surgery. The literature is reviewed and possible
      pathophysiogical mechanisms are discussed.

PMID- 12501982
TI  - Chronic mental illness and the menstrual cycle.
AB  - The purpose of this study was to explore the relationship between chronic mental
      illness, menstrual cycle phases, and psychiatric hospitalization. A detailed
      menstrual history was obtained from each participating subject. Women who were
      pregnant, postmenopausal, or who were prescribed hormonal contraception were
      excluded from the study. Factors precipitating admission, such as a suicide
      attempt, were identified. All women had a documented history of chronic mental
      illness, defined in this study as two prior psychiatric hospitalizations. Based
      on the menstrual history, the phase of the women's cycle at time of
      hospitalization was calculated. Diagnoses and the reasons for admission were
      correlated with the menstrual cycle phase. Thirty-three women participated in the
      study. Seventeen (52%) of those women were admitted during the late luteal/early
      menstrual phase. Women with schizophrenia whose behavior precipitating the
      admission was characterized as nonsuicidal and nonaggressive were admitted
      exclusively during the postovulatory phase. On the basis of findings of this
      study, the authors conclude that the postovulatory phase of the menstrual cycle
      may be a time of increased risk for women with chronic mental illness, especially
      schizophrenia. Prophylactic interventions might minimize admissions.

PMID- 12501983
TI  - Delay of hospital discharge secondary to postoperative fever--is it necessary?
AB  - Although postoperative fever is common after major gynecologic surgery, the
      majority of patients have no identifiable infectious or pathologic etiology.
      Traditional management has been to delay hospital discharge until the patient is
      afebrile. The authors evaluate the outcome of patients discharged with
      postoperative fever after major gynecologic surgery. In a retrospective review of
      537 women undergoing major gynecologic surgery, 211 (39%) had postoperative
      fever. The authors identified all patients who were discharged despite having a
      temperature of 38 degrees C or higher (> or = 100.4 degrees F) in the preceding
      12 hours. All outpatient and inpatient records for a period of 30 days were
      reviewed. Thirty-eight (18%) of 211 patients who were febrile postoperatively
      were discharged despite having a fever within the preceding 12 hours. One patient
      was lost to follow-up. Two (5%) of 37 patients had a documented infection (one
      urinary tract infection and one postoperative wound infection). Four (11%) were
      readmitted within 30 days for noninfectious causes. None of the patients
      discharged on oral antibiotics had an antibiotic-related complication. Eighty
      four percent of patients discharged with a postoperative fever did not have a
      documented infectious or pathologic cause for the fever while at home.

PMID- 12501984
TI  - Curricular and pedagogic questions raised by recent medical education efforts on
      bioterrorism.
AB  - This article outlines the development of learning materials to educate
      osteopathic medical students about biological terrorism at the American
      Association of Colleges of Osteopathic Medicine (AACOM). The author then poses
      two questions that arose from this and concurrent AACOM projects and new
      technologic developments in medical education, regarding what colleges of
      osteopathic medicine teach and how they teach it.

PMID- 12501985
TI  - Reasons for student debt during medical education: a Michigan study.
AB  - The authors address the need for a better understanding of the reasons for
      greater indebtedness among today's osteopathic medical students. In May 2000, a
      survey was mailed to all 219 osteopathic interns at participating institutions in
      Michigan. The self-administered survey contained 19 questions designed to gather
      basic financial information, demographic characteristics, and subjective
      perceptions of student debt loads from participating interns. One hundred seventy
      completed surveys were returned, for a response rate of 78%. The authors
      attempted to focus on demographic predictors of debt and found that although
      there is no indication that such predictors have a significant effect on a
      student's total debt load, financial support from the student's family remains
      the single most important factor in predicting low levels of student debt. The
      authors suggest that the higher debt rate of students entering specialty fields
      may reflect the fact that students incur these debts with the knowledge that
      those debts will be more easily repaid once the student has begun to practice
      medicine.

PMID- 12501986
TI  - Physician-pharmacist collaboration: a millennial paradigm to reduce medication
      errors.
AB  - The Institute of Medicine has reported that medication errors cause an estimated
      7000 deaths annually. Additionally, drug-related adverse events increase the risk
      of mortality by 1.88, with approximately 27% of reported adverse drug events
      attributed to negligence. As the healthcare system is faced with the challenge of
      reducing medication errors and adverse drug events, one viable solution may be to
      increase physician-pharmacist collaboration. According to the recent literature,
      increasing physicianpharmacist collaboration may result in a reduction in total
      drug morbidity and mortality.

PMID- 12501987
TI  - Use of intravenous immunoglobulin in Lambert-Eaton myasthenic syndrome.
AB  - The authors report a case of a 65-year-old woman with small cell lung cancer who
      had profound, progressive lower extremity weakness, intermittent blurred vision,
      a dry mouth, and orthostatic hypotension. Results of laboratory and
      electrodiagnostic studies were consistent with the diagnosis of Lambert-Eaton
      myasthenic syndrome. The patient was treated with one course of intravenous
      immunoglobulin and had significant improvement.

PMID- 12501988
TI  - Alkaline adaptation induces cross-protection against some environmental stresses
      and morphological change in Vibrio parahaemolyticus.
AB  - The relationship between alkaline adaptation and the resistance against
      environmental stresses was examined in Vibrio parahaemolyticus. Alkali-adapted
      cells were found to have increased resistance against various stresses, including
      heat, crystal violet, deoxycholic acid, and hydrogen peroxide. However, alkali
      adapted cells showed no increased resistance against acid stress and heat-adapted
      cells did not show increased resistance against alkaline stress. Furthermore,
      alkaline treatment induced cell elongation with heterogenous size of the
      bacterium.

PMID- 12501989
TI  - Control of Escherichia coli growth rate through cell density.
AB  - The transition from the exponential to the stationary phase of Escherichia coli
      cultures has been investigated regarding nutrient availability. This analysis
      strongly suggests that the declining of the cell division rate is not caused by
      mere nutrient limitation but also by an immediate sensing of cell concentration.
      In addition, both the growth rate and the final biomass achieved by a batch
      culture can be manipulated by altering its density during the early exponential
      phase. This result, which has been confirmed by using different experimental
      approaches, supports the hypothesis that the E. coli quorum sensing is not only
      determined by the release of soluble cell-to-cell communicators. Cell-associated
      sensing elements might also be involved in modulating the bacterial growth even
      in the presence of non-limiting (although declining) nutrient concentrations,
      thus promoting their economical utilisation in dense populations.

PMID- 12501990
TI  - Isolation and identification of yeasts associated with vineyard and winery by
      RFLP analysis of ribosomal genes and mitochondrial DNA.
AB  - Yeast colonies isolated from vineyard and cellar substrates were analysed in the
      present study. Yeast species assessment was carried out by amplification and
      digestion of a region of the ribosomal RNA gene repeat unit. Saccharomyces
      strains were also characterised using mitochondrial DNA restriction analysis.
      Oxidative basidiomycetous yeasts without enological potential were predominant in
      the vineyard environment. Yeasts associated with grape skin depend on grape
      variety, vintage and degree of grape maturation. These species from grape surface
      constituted the predominant microbiota in must and they developed during the
      first stages of the process. Yeasts colonies were also isolated and identified
      from the walls of a fermentation vat some days before the harvest. Contray to
      what was expected, Saccharomyces cerevisiae was not the major species isolated as
      Candida sorbosa represented 76% of the species isolated. Saccharomyces strains
      isolated from the fermentation vat had been previously isolated in wine
      fermentations in this cellar. Therefore, these strains should be considered as
      constant residents of this winery.

PMID- 12501991
TI  - Catalytic properties of the immobilized Aspergillus tamarii xylanase.
AB  - Xylanase from Aspergillus tamarii was covalently immobilized on Duolite A147
      pretreated with the bifunctional agent glutaraldehyde. The bound enzyme retained
      54.2% of the original specific activity exhibited by the free enzyme (120 U/mg
      protein). Compared to the free enzyme, the immobilized enzyme exhibited lower
      optimum pH, higher optimum reaction temperature, lower energy of activation,
      higher Km (Michaelis constant), lower Vmax (maximal reaction rate). The half-life
      for the free enzyme was 186.0, 93.0, and 50.0 min for 40, 50, and 60 degrees C,
      respectively, whereas the immobilized form at the same temperatures had half-life
      of 320, 136, and 65 min. The deactivation rate constant at 60 degrees C for the
      immobilized enzyme is about 6.0 x 10(-3), which is lower than that of the free
      enzyme (7.77 x 10(-3) min). The energy of thermal deactivation was 15.22 and
      20.72 kcal/mol, respectively for the free and immobilized enzyme, confirming
      stabilization by immobilization. An external mass transfer resistance was
      identified with the immobilization carrier (Duolite A147). The effect of some
      metal ions on the activity of the free and immobilized xylanase has been
      investigated. The immobilized enzyme retained about 73.0% of the initial
      catalytic activity even after being used 8 cycles.

PMID- 12501992
TI  - Colony variation in Sinorhizobium meliloti inoculant strain U 45.
AB  - A culture of Sinorhizobium meliloti strain U 45, maintained on yeast extract
      mannitol (YM) agar, produced a mixture of Congo red-absorbing (R1) and non
      absorbing (W1) colonies when grown on YM medium containing Congo red. The
      original freeze-dried (FD) culture formed gummy (G), white (W2) and small red
      (R2) colony types on the above medium. All colonies were stable except G, which
      segregated into G and W2-like types. Immune diffusion patterns of all colony
      types were identical. The W1 colony type dominated R1 when a 1:1 combination was
      sub-cultured on YM agar. The parent cultures and their variants exhibited a range
      of N2-fixing effectiveness and competitiveness when inoculated onto two cultivars
      of Medicago sativa. Variant R2 from the FD culture was ineffective on both
      cultivars. Genomic DNA fingerprinting with insertion elements ISRm3 and ISRm2011
      2 suggested that transposition of these elements was not a cause of variation,
      but a DNA band was absent in the profiles of two out of three W2-like colonies.
      Protein profile comparisons showed high similarity (r = 0.98) between the colony
      types when grown in YM broth. When grown on Tryptone-Yeast extract medium,
      variants from the FD and agar-maintained cultures formed separate clusters with r
      = 0.79. Polymerase chain reaction fingerprinting using repetitive, site-directed
      and arbitrary primers failed to differentiate the variants. The results emphasize
      the need to monitor culture variability to maintain the quality of legume
      inoculants.

PMID- 12501993
TI  - Lectin-like binding and antibiotic sensitivity of enterococci from wild
      herbivores.
AB  - Fifty eight enterococcal isolates from wild herbivores were tested for their
      antibiotic sensitivity pattern and lectin-like binding of extracellular matrix
      (ECM) and serum proteins. Kanamycin resistance was very frequent; many
      multiresistant strains were also isolated. All isolates were sensitive to
      rifampicin. Resistance to gentamicin, novobiocin, and tetracycline was widely
      distributed in the microflora of wild herbivores breeded in zoological garden in
      Kosice. No autoaggregating strains were detected among these 58 enterococcal
      isolates. Various degrees of binding of mucins, fetuin, heparin, fibrinogen, and
      fibronectin were observed in individual strains. However, bovine lactoferrin
      binding by enterococci from deers and chamoises was either negative (0) or
      strongly positive (3). With regard to influence of growth media, TH agar was
      found to be better for the expression of lectin-like binding than blood agar, TH
      broth and Nutrient broth. A significant effect (P < 0.001 or P < 0.05) of
      proteolytic treatment was observed in six selected strains. However, there is a
      difference between the effect of trypsin and pronase P. Pronase treatment more
      effectively decreased binding of some strains (1H, 6A, EF 1111, EC 1292), while
      trypsin treatment decreased more binding of other enterococcal strains (EF 953
      and 1E). Significant (P < 0.001) influence of metaperiodate, which cleaves the C
      C bond between vicinal groups of sugars, on collagen I binding by three selected
      strains (1E, 1H, 6A) and bovine lactoferrin binding (by EF 1111, EC 1292, EF 953)
      was also observed. However, its influence was very different. In two strains (1H
      and EC 1292), ECM binding was decreased, while in four other strains (1E, 6A, EF
      1111, EF 953) it was increased.

PMID- 12501994
TI  - Genetic studies on reference strains of mutans streptococci.
AB  - Twenty four reference strains (serotype a-h) belonging to the mutans group of
      streptococci were compared for DNA fragment patterns of rDNA after treatment with
      Hind III. It was shown that Streptococcus cricetus (serotype a), S. rattus
      (serotype b), and S. downei (serotype h) reveals comparatively homogeneous
      patterns while S. mutans (serotype c, e and f) exhibits differences between the
      different serotypes as well as within single serotypes. S. sobrinus had an
      intermediary diversity. These data support the previous findings that S. mutans
      is heterogeneous at the serological, biochemical and genetical level.

PMID- 12501995
TI  - Several pseudomonads, associated with the cultivated mushrooms Agaricus bisporus
      or Pleurotus sp., are hemolytic.
AB  - Pseudomonas tolaasii, causing brown blotch disease on cultivated mushrooms, and
      yielding a white line precipitate towards P. "reactans", has been shown to induce
      lysis of erythrocytes. Some Finnish strains isolated from diseased mushroom fruit
      bodies, although harboring the typical features of P. tolaasii, proved to be
      distinct, and have been allocated to a nov. sp. P. costantinii. We examined in
      these study whether all brown blotch causing agents were hemolytic. The induction
      of erythrocytes lysis seemed to be a rather common feature of mushroom associated
      pseudomonads, especially for strains involved in the production of a white-line
      in agar.

PMID- 12501996
TI  - The two enantiospecific dichlorprop/alpha-ketoglutarate-dioxygenases from Delftia
      acidovorans MC1--protein and sequence data of RdpA and SdpA.
AB  - Two alpha-ketoglutarate-dependent dioxygenases carrying enantiospecific activity
      for the etherolytic cleavage of racemic phenoxypropionate herbicides [(RS)-2-(2,4
      dichlorophenoxy)propionate and (RS)-2-(4-chloro-2-methylphenoxy)propionate] from
      Delftia acidovorans MC1 were characterized with respect to protein and sequence
      data. The (S)-phenoxypropionate/alpha-ketoglutarate-dioxygenase (SdpA) appeared
      as a monomeric enzyme with a molecular weight of 32 kDa in the presence of SDS. N
      terminal sequences revealed relationship to alpha-ketoglutarate-dependent taurine
      dioxygenase (TauD) and to 2,4-dichlorophenoxyacetate/alpha-ketoglutarate
      dioxygenase (TfdA). The (R)-phenoxypropionate/alpha-ketoglutarate-dioxygenase
      (RdpA) referred to 36 kDa in the presence of SDS and to 108 kDa under native
      conditions. Internal sequences of fragments obtained after digestion made evident
      relationship to TfdA and TauD. Two-dimensional electrophoretic separation
      resulted in the resolution of up to 3 individual spots with almost identical
      molecular weights but different isoelectric points with both RdpA and SdpA. The
      structural differences of these isoenzyme forms are not yet clear.

PMID- 12501997
TI  - Contribution of ferrous iron to maintenance of the gastric colonization of
      Helicobacter pylori in miniature pigs.
AB  - Our previous study showed that the colonization levels of Helicobacter pylori
      were higher in the stomachs of 5-day-old miniature pigs than in 2-week-old ones.
      As dietary factors can cause these differences, we compared two diets, i.e.,
      Weanymilk and a similar formula with a higher concentration of Fe(II),
      Weanylobulin. The colonization levels in the fundic mucosa were significantly
      higher in 2-week-old pigs fed Weanylobulin than in those fed Weanymilk.
      Supplementing Weanylobulin with an iron chelator, deferoxamine mesylate,
      significantly lowered the bacteria counts in the gastric mucosa. Normal diets
      supplemented with Fe(II) in 2-month-old pigs caused significantly more sites of
      bacteria in the antrum compared with normal diets alone. In addition, ranitidine,
      an inhibitor of gastric acid secretion that reduces Fe(III) to Fe(II) in the
      stomach, decreased the bacteria counts in 10-month-old pigs. These results
      suggested that Fe(II) maintained the colonization levels of H. pylori in the
      stomach of the miniature pigs.

PMID- 12501998
TI  - Comparison of the potential of coastal materials loaded with bacteria for
      bioremediating oily sea water in batch culture.
AB  - The objective of this paper was to study whether the bioremediation potential of
      coastal materials for oil-polluted sea water depended on the numbers of
      hydrocarbon-utilizing bacteria they naturally harbor. Inshore water of the
      Arabian Gulf was found to contain only about one thousand hydrocarbon-utilizing
      bacteria per ml. Coastal sand, cyanobacterial mats and epilithic biomass were
      much richer in these bacteria, with numbers ranging between several thousand fold
      to several million fold than in the water body. The predominant bacterium in all
      samples was Acinetobacter calcoaceticus, next in predominance were nocardioforms
      and Micrococcus sp. Inoculation, in batch cultures, of oily sea water or sea
      water containing pure hydrocarbons with fresh sea water, coastal sand,
      cyanobacterial mats or epilithic biomass harboring significantly different
      numbers of hydrocarbon-utilizing bacteria brought bioremediation effects that
      depended on fertilizing with KNO3. In the absence of KNO3, the bioremediation
      effect increased with numbers of hydrocarbon-utilizing bacteria in the inoculum.
      In the presence of KNO3 similar bioremediation effects were found irrespective of
      the inoculated materials. The reason may be that bacteria reproduce quickly in
      closed cultures provided with nitrogen, reaching equal maximum numbers,
      irrespective of the inoculum size. This information could be useful in
      constructing technologies for oily sea water bioremediation.

PMID- 12501999
TI  - Structural features of the glycogen branching enzyme encoding genes from
      aspergilli.
AB  - A maltose binding protein, p78, was purified to homogeneity from Aspergillus
      nidulans by a single column chromatography step on cross-linked amylose. The
      partial amino acid sequence was highly homologous to the glycogen branching
      enzymes (GBEs) of human and yeast, and p78 did show branching enzyme activity.
      The genomic gene and its cDNA encoding GBE (p78) were isolated from the A.
      nidulans genomic and cDNA libraries. Furthermore, a cDNA encoding A. oryzae GBE
      was entirely sequenced. A. nidulans GBE shared overall and significant amino acid
      sequence identity with GBEs from A. oryzae (83.9%), Saccharomyces cerevisiae
      (61.1%) and human (63.0%), and with starch branching enzymes from green plants
      (55-56%).

PMID- 12502000
TI  - Structural integrity of polypropylene prosthetic sockets manufactured using the
      polymer deposition technique.
AB  - Rapid prototyping (RP) technology has been used recently as a means for automated
      socket fabrication. Although the technology has proven to be promising and has
      truly automated the socket fabrication process, the structural integrity of RP
      sockets remains questionable. For the long term, unsupervised use of these
      'unconventional' sockets, their material properties and structural integrity must
      be determined. This study investigated the structural integrity of polypropylene
      sockets manufactured using a polymer deposition technique, in which a socket is
      formed by a continuous strand of partially melted polypropylene that is spirally
      deposited according to the socket's cross-sectional contour. To investigate the
      problem of delamination of the socket, the tensile properties of the socket
      material were determined according to ASTM D638-99. The ultimate tensile strength
      was found to be approximately 13-23 per cent lower than that of polypropylene
      sheets that are at present normally used for socket fabrication. In order to
      improve the load-bearing capacity of the socket, it was reinforced using a double
      wall arrangement at the distal region, where failure normally occurs. The
      structural integrity of the complete prosthesis was then investigated according
      to ISO 10328 (loading condition II). The prosthesis passed the static loading
      test registering only 12 mm permanent deformation, and it successfully completed
      a preliminary cyclic test of 250,000 cycles with no observable failure.

PMID- 12502001
TI  - Characterization of microfeatures in selective laser sintered drug delivery
      devices.
AB  - From initial applications in the fields of prosthesis, implants, surgery
      planning, anthropology, paleontology and forensics, the scope of rapid
      prototyping (RP) biomedical applications has expanded to include areas in tissue
      engineering (TE) and controlled drug delivery. In the current investigation, the
      feasibility of utilizing selective laser sintering (SLS) to fabricate polymeric
      drug delivery devices (DDDs) that are difficult to make using conventional
      production methods was studied. Two features, namely porous microstructure and
      dense wall formation, inherent in SLS fabricated parts were investigated for
      their potential roles in drug storage and controlling the release of drugs
      through the diffusion process. A study to determine the influence of key SLS
      process parameters on dense wall formation and porous microstructure of SLS
      fabricated parts was carried out. Composite-type DDDs incorporating dense wall
      and porous matrix features were designed and fabricated using SLS. The
      characteristics of the fabricated devices were investigated through
      microstructural examination and in vitro release tests carried out using a drug
      model or dye in a simulated body environment.

PMID- 12502002
TI  - A new capillary viscometer for small samples of whole blood.
AB  - A new capillary viscometer is described in which a column of blood is discharged
      under a constant pressure, producing a variety of shear stresses during a single
      test. Measurement of the viscosity of Newtonian sucrose solutions showed good
      agreement between the viscosity determined from the new system and the expected
      values. The viscosity of whole blood was measured in a cone-and-plate viscometer
      at a wide range of shear rates and characterized using a power law model; good
      agreement was obtained between the capillary and rotational results at low and
      medium shear rates. High shear rate results could also be obtained by increasing
      the driving pressure. The new viscometer proved to be simple to use, utilized a
      small test volume and produced reliable results.

PMID- 12502003
TI  - The influence of shape and sliding distance of femoral head movement loci on the
      wear of acetabular cups in total hip arthroplasty.
AB  - Wear of the polyethylene acetabular component is the most serious threat to the
      long-term success of total hip replacements (THRs). Greatly reduced wear rates
      have been reported for unidirectional, compared to multidirectional, articulation
      in vitro. This study considers the multidirectional motions experienced at the
      hip joint as described by movement loci of points on the femoral head for
      individual THR patients. A three-dimensional computer program determined the
      movement loci of selected points on the femoral head for THR patients and normal
      subjects using kinematic data obtained from gait analysis. The sizes and shapes
      of these loci were quantified by their sliding distances and aspect ratios with
      substantial differences exhibited between individual THR patients. The average
      sliding distances ranged from 10.0 to 18.1 mm and the average aspect ratios of
      the loci ranged from 2.5 to 9.2 for the THR patients. Positive correlations were
      found between wear rate and average sliding distance, the inverse of the average
      aspect ratio of the loci and the product of the average sliding distance and the
      inverse of the average aspect ratio of the loci. Patients with a normal hip joint
      range of motion produce multidirectional motion loci and tend to experience more
      wear than patients with more unidirectional motion loci. Differing patterns of
      multidirectional motion at the hip joint for individual THR patients may explain
      widely differing wear rates in vivo.

PMID- 12502004
TI  - Effect of microseparation on contact mechanics in ceramic-on-ceramic hip joint
      replacements.
AB  - The contact mechanics in ceramic-on-ceramic hip implants are investigated in this
      study under the microseparation condition where the edge contact occurs between
      the superolateral rim of the acetabular cup and the femoral head. A three
      dimensional finite element model is developed to examine the effect of the
      microseparation distance between the femoral head and the acetabular cup on the
      contact area and contact stresses between the bearing surfaces. It is shown that
      microseparation leads to edge contact and elevated contact stresses, and these
      are mainly dependent on the magnitude of separation, the radial clearance between
      the femoral head and the acetabular cup, and the cup inclination angle. For a
      small microseparation distance (less than the diametrical clearance), the contact
      occurs within the acetabular cup, and consequently an excellent agreement of the
      predicted contact pressure distribution is obtained between the present three
      dimensional anatomical model and a simple two-dimensional axisymmetric model
      adopted in a previous study [5]. However, as microsegregation is increased
      further, edge contact between the superolateral rim and the femoral head occurs.
      Consequently, the predicted contact pressure is significantly increased. The
      corresponding contact area resembles closely the stripe wear pattern observed on
      both clinically retrieved and simulator-tested ceramic femoral heads [8, 9, 11].
      Furthermore, introducing a fillet radius of 2.5 mm at the mouth of the acetabular
      cup is shown to reduce the contact stress due to edge contact, but only under
      relatively large microseparation distances.

PMID- 12502005
TI  - Effect of stair descent loading on ultra-high molecular weight polyethylene wear
      in a force-controlled knee simulator.
AB  - A loading protocol approximating forces, torques and motions at the knee during
      stair descent was developed from previously published data for input into a force
      controlled knee simulator. A set of total knee replacements (TKRs) was subjected
      to standard walking cycles and stair descent cycles at a ratio of 70: 1 for 5
      million cycles. Another set of implants with similar articular geometry and the
      same ultra-high molecular weight polyethylene (UHMWPE) resin (GUR 415),
      sterilization and packaging was tested with standard walking cycles only. Implant
      kinematics, gravimetric wear and surface roughness of the UHMWPE inserts were
      analysed for both sets of implants. Contact stresses were calculated for both
      loading protocols using a Hertzian line contact model. Significantly greater
      weight loss (p < 0.05) and more severe surface damage of UHMWPE inserts resulted
      with the walking + stair descent loading protocol compared to walking cycles
      only. Anterior-posterior (AP) tibiofemoral contact point displacements were lower
      during stair descent than walking, but not significantly different (p = 0.05).
      Contact stresses were significantly higher during stair descent than walking,
      owing to higher axial loads and the smaller radius of curvature of the femoral
      components at higher flexion angles. High contact stresses on UHMWPE components
      are likely to accelerate the fatigue of the material, resulting in more severe
      wear, similar to what is observed in retrieved implants. Thus the inclusion of
      loading protocols for activities of daily living in addition to walking is
      warranted for more realistic in vitro testing of TKRs.

PMID- 12502006
TI  - Surface characterization and debris analysis of ceramic pairings after ten
      million cycles on a hip joint simulator.
AB  - This study was aimed at characterizing the ceramic wear particles produced during
      tests on a hip joint wear simulator of up to 10 million cycles. Alumina and
      alumina-zirconia composites were studied as commercial or potential hip joint
      products respectively. No ceramic particles could be observed, even after a
      careful isolation procedure. This confirms the low wear rate found for these
      materials in previous works (of the order of tenths of milligrams per million
      cycles). Surface characterization was conducted by means of scanning electron
      microscopy. It confirms the low wear regime of ceramic pairings and allows
      ceramic wear debris morphology to be defined. The effect of microstructure on
      surface wear is discussed.

PMID- 12502007
TI  - Prediction of skin burn injury. Part 1: numerical modelling; part 2: parametric
      and sensitivity analysis.

PMID- 12502008
TI  - Insight in persons with schizophrenia: effects of switching from conventional
      neuroleptics to atypical antipsychotics.
AB  - The primary aim of our study is to evaluate the level of insight during the
      switch from a classical antipsychotic drug to a atypical neuroleptic. Twenty-two
      schizophrenic patients were admitted to the study, 9 were male and 13 were
      female. Standardized questionnaire were: Scale for Assessment of Negative
      Symptoms (SANS), Scale for Assessment of Positive Symptoms (SAPS), Brief
      Psychiatric Rating Scale (BPRS) and Schedule for Assessing the three components
      of Insight (SAI). All patients were receiving haloperidol at time of recruitment.
      Eight patients were switched to clozapine, 3 to risperidone and 11 to olanzapine.
      The global function, measured with BPRS, increased after administration of
      atypical antipsychotics. The positive and negative symptoms were reduced. The
      level of insight was increased after the administration of the atypical
      antipsychotics. The cognitive effect of the atypical antipsychotics changed the
      level of insight and augmented the compliance.

PMID- 12502009
TI  - The effects of paroxetine and tianeptine on peripheral biochemical markers in
      major depression.
AB  - Depression is related to the alterations of the central serotonergic system and
      some antidepressants achieve their therapeutic effects through alteration of
      serotonin (5-HT) (re)uptake. Peripheral biochemical markers, platelet and serum 5
      HT concentrations, platelet monoamine oxidase (MAO) activity, plasma levels of
      cortisol and prolactin (PRL), were investigated in patients with major depression
      before and after 4 weeks of treatment with paroxetine (an inhibitor of 5-HT
      uptake) or tianeptine (a stimulator of 5-HT uptake). Study was open, single
      center and included female depressed patients, 21 treated with tianeptine (37.5
      mg/day) and 15 treated with paroxetine (20 mg/day), and 11 drug-free healthy
      women (controls). Before treatment, depressed patients as a group had
      significantly higher serum 5-HT and cortisol concentrations than healthy
      controls. There were no differences in the other biochemical markers. Response to
      antidepressant treatment was estimated according to the 50% fall in the initial
      scores of Hamilton Depression Rating Scale (HAMD) after 4 weeks of treatment.
      Good therapeutic response was observed in 47% and 45% patients treated with
      paroxetine and tianeptine, respectively. Paroxetine treatment induced significant
      decrease in platelet 5-HT concentrations in both responders and nonresponders,
      while no alterations in platelet 5-HT values were found in tianeptine-treated
      patients. There was a subgroup of depressed patients in paroxetine-treated group
      with high pretreatment platelet 5-HT concentration and later poor therapeutic
      response to paroxetine treatment. Serum 5-HT values, platelet MAO activity or
      plasma cortisol or PRL levels were unchanged after both treatments. The results
      suggest that pretreatment platelet 5-HT levels, but not other peripheral
      biochemical markers, might predict therapeutic outcome at least in paroxetine
      treated patients.

PMID- 12502010
TI  - Comorbidity of Tourette's syndrome and schizophrenia--biological and
      physiological parallels.
AB  - The authors report on five patients who first developed Tourette's syndrome (TS)
      and later schizophrenia with the typical positive and negative symptoms; all five
      had an unfavorable course of schizophrenia. These observations as well as other
      reported cases raise the question of whether both disorders may share a common
      background. This is discussed under the aspects of similar symptomatology
      (echolalia, motor symptoms, cognitive deficits, obsessive-compulsive symptoms),
      similar pathophysiological signs, genetics and signs of an underlying
      inflammatory process in subgroups of cases, as well as common therapeutic
      strategies. A genetically determined susceptibility could possibly underlie both
      disorders, e.g., an autoimmunologically triggered inflammation or a common
      pathophysiology of certain symptoms. Both disorders show disturbances of the
      multiple functional pathways, which seem to be involved in the pathophysiology of
      both. The clinical overlap of TS and of schizophrenia may be due to a final
      common pathophysiological pathway.

PMID- 12502011
TI  - Endocrinological effects of mirtazapine in healthy volunteers.
AB  - OBJECTIVE: Unlike other antidepressants, mirtazapine does not inhibit the
      reuptake of norepinephrine or serotonin (5-HT) but acts as an antagonist at
      presynaptic alpha2-receptors and at postsynaptic 5-HT2, 5-HT3 and histamine H1
      receptors. In the present investigation, the influence of acute oral
      administration of 15-mg mirtazapine on the cortisol (COR), adrenocorticotropin
      (ACTH), growth hormone (GH) and prolactin (PRL) secretion was examined in 12
      healthy male subjects, compared to placebo. METHODS: After insertion of an
      intravenous catheter, both the mean arterial blood pressure (MAP) and the heart
      rate were recorded and blood samples were drawn 1 h prior to the administration
      of mirtazapine or placebo (7:00 a.m.), at time of administration (8:00 a.m.) and
      during 5 h thereafter in periods of 30 min. Concentrations of COR, ACTH, GH and
      PRL were measured in each blood sample by double antibody radioimmunoassay and
      chemiluminescence immunoassay methods. The area under the curve (AUC; 0-300 min
      after mirtazapine or placebo administration) was used as parameter for the COR,
      ACTH, GH and PRL response. Furthermore, the urinary free cortisol excretion (UFC)
      was determined beginning at 8:00 a.m. (time of administration of placebo or
      mirtazapine) up to 8:00 a.m. the day after. RESULTS: Two-sided t-tests for paired
      samples revealed significantly lower COR AUC, ACTH AUC, UFC and PRL AUC values
      after 15-mg mirtazapine compared to placebo, whereas no significant differences
      were found with respect to GH AUC, MAP and heart rate. CONCLUSIONS: Since the
      acute inhibition of COR secretion in the healthy volunteers was paralleled by a
      simultaneous decrease of ACTH release, central mechanisms (e.g., inhibition of
      hypothalamic corticotropin releasing hormone (CRH) output) are suggested to be
      responsible for the inhibitory effects of mirtazapine on COR secretion. Our
      results are of particular interest in the light of the hypercortisolism observed
      in depressed patients and new pharmacological approaches such as CRH1 receptor
      antagonists.

PMID- 12502012
TI  - Effects of DA D1 and D2 antagonists on the sensitisation to the motor effects of
      morphine in mice.
AB  - Acute morphine administration produces hyperactivity in mice and repeated
      treatment induces an enhancement of this effect. In this experiment, we study the
      sensitisation to the hyperactivity induced by intermittent morphine
      administration (40 mg/kg) and the effects of dopamine (DA) antagonists on this
      phenomenon. Animals received three injections, separated by 48 h, and after each
      injection, their activity was registered between 30 and 60 min. In Experiment 1,
      animals were divided into two groups, which received saline and morphine (S-S-M)
      or only morphine (M-M-M). In Experiment 2, animals were divided into 12 groups.
      Half, which was designed to study the effects of DA antagonists on the
      acquisition of morphine sensitisation, received morphine plus 0.125, 0.25, or 0.5
      mg/kg SCH 23390 or raclopride in the two first administrations and only morphine
      in the third (M+SCH-M+SCH-M; M+R-M+R-M). The other groups, designed to study the
      effects of DA antagonists on the expression of morphine sensitisation, received
      morphine in the two first administrations and morphine plus DA antagonists in the
      last injection (M-M-M+SCH; M-M-M+R). Intermittent morphine administration
      produces greater hyperactivity than acute morphine. DA D1 antagonists reduce
      acquisition and block expression of sensitisation, while DA D2 antagonists only
      affect expression with the intermediate and high dose. These results support the
      implication of DA in the behavioural sensitisation of morphine in mice.

PMID- 12502013
TI  - Support for the presence of bipolar disorder susceptibility loci on chromosome 5:
      heterogeneity in a homogeneous population in Quebec.
AB  - A very large pedigree derived from the Saguenay-Lac-St-Jean region of Quebec
      contains a branch where a distal chromosome 5q haplotype seems to cosegregate
      with bipolar affective disorder. The authors used a diagnosis model where Bipolar
      Types I and II and schizoaffective disorder bipolar type were considered as
      affected, while single or recurrent episode major depression was classified as
      unknown and all the others diagnoses as unaffected. Model-free two-point LOD
      score values of 3.41 and 2.21 were observed at D5S432 in the 5p region with
      sib_ibd and sib_phase from the ASPEX package, but simulation studies did not
      permit the conclusion of a significant linkage because associated empirical P
      values were equal to .0026 and .0037. A parametric LOD score value of 2.15 was
      obtained at locus D5S412 in the distal chromosome 5q area. In order to
      investigate heterogeneity in the single multigenerational family, the pedigree
      was divided into five branches. Our simulation study suggested that the five
      branches of the Saguenay-Lac-St-Jean bipolar pedigree had low power to detect
      linkage under intrapedigree heterogeneity in this region.

PMID- 12502014
TI  - Monoamine oxidase: A gene polymorphism, tryptophan hydroxylase gene polymorphism
      and antidepressant response to fluvoxamine in Japanese patients with major
      depressive disorder.
AB  - Monoamine oxidase A (MAOA) and tryptophan hydroxylase (TPH) are the staple
      enzymes in the metabolism of serotonin (5-HT). The genetic polymorphisms of these
      two enzymes might individually alter the production, release, reuptake or
      degradation of 5-HT during the treatment of selective serotonin reuptake
      inhibitors (SSRIs), leading to the individual differences in the antidepressant
      effects of SSRIs. The authors investigated whether a functional polymorphism in
      the MAOA gene promoter (MAOA-VNTR) and a TPH gene polymorphism in intron 7 (TPH
      A218C) were associated with the antidepressant response to fluvoxamine in 66
      Japanese patients with major depressive disorder during a 6-week study with a
      specific dosage plan. Fifty-four patients completed the study. The present study
      fails to demonstrate that the genetic polymorphisms of MAOA-VNTR and TPH-A218C
      affect the antidepressant effect of fluvoxamine in Japanese patients with major
      depressive disorder.

PMID- 12502015
TI  - Neuroanatomical correlates of low body weight in Alzheimer's disease: a PET
      study.
AB  - Weight loss is a common problem in patients with Alzheimer's disease (AD) and
      this might be associated with an increased risk for mortality. Recent evidences
      have suggested that certain brain dysfunctions may result in impaired nutritional
      status in AD patients. However, the mechanism of body weight loss in AD remains
      enigmatic. To investigate a possible association between low body weight and
      regional brain dysfunction, the authors conducted the correlational analysis of
      body mass index (BMI) with regional brain glucose metabolism using positron
      emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Twenty-seven
      patients with probable AD were divided into two groups: the low BMI group and the
      normal BMI group. Regional brain glucose metabolic ratios were calculated using
      the cerebellar hemisphere as a reference region. Comparisons were made of
      regional brain metabolic ratios between the low BMI group and the normal BMI
      group. Correlations of the glucose metabolic ratio with BMI were also assessed in
      all patients with AD. In the comparison between the two groups, glucose metabolic
      ratio in the anterior cingulate cortex (ACC) was significantly lower in the low
      BMI group, whereas no significant differences were found in all the other brain
      regions. Furthermore, regional glucose metabolism in the ACC had a significant
      and positive correlation with BMI (r=.450, P=.018). After adjustment for age,
      gender and disease duration, regional glucose metabolism in the ACC was
      independently associated with BMI. Our findings suggest that the ACC may be
      preferentially involved in the regulation of nutritional status in AD patients,
      and provides a new insight into developing strategies for prevention and
      treatment of undernutritional demented patients.

PMID- 12502016
TI  - Selective impairments in rats on an odor-guided continuous delayed nonmatching-to
      sample (cDNMS) task after fornix transection.
AB  - The two experiments reported in this article examined recognition of simple and
      complex olfactory stimuli. In Experiment 1, three groups of control rats were
      trained to criterion without delay then, tested with delays on a continuous
      delayed nonmatching-to-sample (cDNMS) task using one of three kinds of odor
      pairs: replicates of the same odor (S), different odors that were each common
      with another pair (O), different odors with no overlap between pairs (NO).
      Results showed that initial learning and performance with delays were both poorer
      for O pairs than for S and NO pairs. Experiment 2 used a within-subject design to
      study the effects of fornix transection on recognition of the same three kinds of
      odor pairs as those described for Experiment 1. Sham-operated controls and rats
      (SH) with fornix transection were trained to criterion prior to the test with
      delays first on S, then on O and, finally, on NO pairs. During training, numbers
      of sessions to criterion did not differ in lesioned and SH rats on any of the
      three kinds of pairs. During testing, the level of performance was delay
      dependent in both groups. However, lesioned rats were significantly impaired when
      tested with S and O pairs, but did not differ from sham-operated controls when
      tested with NO pairs. This selective impairment can be interpreted as evidence
      that fornix lesions impair recognition memory of stimuli that provide few and/or
      confusing retrieval cues. It might also suggest that postlesional performance on
      DNMS procedures depends on task difficulty.

PMID- 12502017
TI  - Dopaminergic effects after chronic treatment with nandrolone visualized in rat
      brain by positron emission tomography.
AB  - Anabolic-androgenic steroids (AAS) have recently been shown to induce
      neurochemical alterations in areas of the male rat CNS related to behavioural
      changes that have been observed among AAS misusers. In the present study,
      positron emission tomography (PET) is suggested as a suitable in vivo method in
      order to visualize the density of the dopamine transporter ([11C]-FE-beta-CIT) as
      well as the dopamine D1-like ([11C]-(+)-SCH23390) and the D2-like receptors
      ([11C]-raclopride) in the male rat brain. Chronic treatment with the AAS
      nandrolone decanoate (15 mg/kg/day for 14 days) caused an up-regulation of the
      binding potential of the dopamine transporter in the striatum.

PMID- 12502018
TI  - Lack of effect of acute, subchronic, or chronic stress on glycogen synthase
      kinase-3beta protein levels in rat frontal cortex.
AB  - Glycogen synthase kinase (GSK)-3beta is a conserved serine/threonine protein
      kinase highly abundant in brain tissue. A dominant mechanism by which cells react
      to stress involves GSK-3beta. We studied the effect of stress on GSK-3beta levels
      ex vivo. We have previously found reduced GSK-3beta protein levels and GSK-3
      activity in postmortem prefrontal cortex of schizophrenic patients. Since
      schizophrenic patients experience stress more severely than healthy people, we
      questioned whether their GSK-3beta reduction is stress-related using a rat model.
      Rats were exposed to acute, subchronic, or chronic stress using brief cold
      restraint. No effect was found on frontal cortex GSK-3beta protein levels. These
      results suggest that reduction in GSK-3beta levels in schizophrenic patients is
      not affected by cold restraint stress and supports the possibility that the
      changes observed in postmortem brains may be related to the disease.

PMID- 12502019
TI  - Outcomes and costs of treatment with risperidone in adult and elderly patients:
      the Delta patient using risperidone study.
AB  - PURPOSE: The primary aim of the present study (called DePUR: Delta patients using
      risperidone) was to compare patient characteristics, treatment outcome variables
      and medication costs of adult and elderly patients treated with risperidone.
      METHODS: In a single-centre retrospective study, the following data were
      extracted from the medical records of 32 adult (< 65 years) and 32 elderly (> or
      = 65 years) inpatients to whom risperidone was prescribed shortly after
      admission: demographic data, diagnosis, medication and hospitalisation history,
      all drugs taken during admission, treatment effectiveness of risperidone,
      reported adverse events. These data were collected for the period from admission
      until discharge or until they had been hospitalised for 120 days. RESULTS: Most
      patients (81% of adult patients and 91% of elderly patients) received risperidone
      for a psychiatric disease other than schizophrenia. In elderly patients, major
      depressive disorder with psychotic features was the most frequent diagnosis.
      Treatment with risperidone was in most cases effective (72% and 74%,
      respectively), but effectiveness was established sooner in the adult patients
      than in the elderly patients (7 versus 14 days). The length of stay in hospital
      was shorter in adults than in elderly (38.5 versus 92.7 days). The daily dose of
      risperidone was higher in adults than in elderly patients (3.6 versus 1.7 mg per
      day). Contrary to expectations, daily drug cost of risperidone and daily drug
      cost of all inpatient drugs were not cheaper in adult patients than in the
      elderly, mainly due to a higher dose of risperidone and a higher consumption of
      antipsychotic co-medication in adults. CONCLUSION: Risperidone is prescribed
      successfully for many other psychotic features than for schizophrenia. Treatment
      of elderly patients in our clinic does not require higher daily medication costs
      than for adult patients.

PMID- 12502020
TI  - The influence of MK-801 on the hippocampal free arachidonic acid level and Na+,K+
      ATPase activity in global cerebral ischemia-exposed rats.
AB  - The influence of 20 min global cerebral ischemia on the free arachidonic acid
      (FAA) level and Na+,K+-ATPase activity in the rat hippocampus at different time
      points after ischemia was examined. In addition, the effect of MK-801 on
      mentioned parameters was studied. Animals were exposed to 20 min global cerebral
      ischemia and were sacrificed immediately, 0.5, 1, 2, 6, 24, 48, 72, and 168 h
      after ischemic procedure. The level of the FAA and the Na+,K+-ATPase activity was
      measured during all reperfusion periods examined. Various doses of MK-801 (0.3,
      1.0, 3.0, and 5.0 mg/kg) had been injected 30 min before ischemic procedure
      started. It was found that 20 min global cerebral ischemia induces a
      statistically significant increase of the FAA level immediately after ischemia
      and during the first 0.5 h of reperfusion. After a transient decrease, the level
      of FAA level increased again after 24 and 168 h of recirculation. Treatment with
      3.0 mg/kg of MK-801 significantly prevented the FAA accumulation immediately and
      0.5 h after ischemic insult while application of 5.0 mg/kg of MK-801 exerted a
      protective effect during the first 24 h. Global cerebral ischemia induces the
      significant decline in the Na+,K+-ATPase activity in the hippocampus starting
      from 1 to 168 h of reperfusion. Maximal inhibition was obtained 24 h after the
      ischemic damage. Application of 3.0 mg/kg of MK-801 exerted statistically
      significant protection during the first 24 h while the treatment with 5.0 mg/kg
      of MK-801 prevented fall in enzymatic activity during all reperfusion periods
      examined. Our results suggest that, in spite of different and complex
      pathophysiological mechanisms involved in the increase of FAA level and the
      decrease of the Na+,K+-ATPase activity, blockade of NMDA receptor subtype
      provides a very important strategy for the treatment of the postischemic
      excitotoxicity.

PMID- 12502021
TI  - Hyperhidrosis in social anxiety disorder.
AB  - PURPOSE: Excessive sweating (hyperhidrosis) is an overlooked and potentially
      disabling symptom, which is often seen in social anxiety disorder (SAD). We
      conducted a retrospective review of data acquired in patients with SAD who had
      participated in placebo-controlled clinical trials of fluoxetine, cognitive
      behavior therapy, clonazepam and gabapentin. Four specific topics were addressed:
      (1) overall levels of sweating; (2) characteristics of those with hyperhidrosis;
      (3) a comparison of active treatments relative to placebo on hyperhidrosis; and
      (4) an examination of baseline sweating severity as a predictor of treatment
      outcome. METHODS: Using the Brief Social Phobia Scale (BSPS) and Social Phobia
      Inventory (SPIN), we examined the above questions. RESULTS: Hyperhidrosis was
      found in 24.8-32.3% of 375 subjects assessed, depending upon the scale used.
      Hyperhidrosis was associated with higher levels of disability, fear, avoidance,
      and other physiologic symptoms. While treatment in general was associated with a
      reduction in the rate of hyperhidrosis from 23.7% to 9.7% (BSPS), and 34.0% to
      15.5% (SPIN), only fluoxetine differed significantly from placebo in respect of
      change in sweating score from baseline to endpoint. In an ANCOVA, gabapentin
      differed from placebo on the SPIN. CONCLUSION: We conclude that hyperhidrosis is
      frequently seen in patients with SAD, and that its response to treatment is
      variable. Further attention should be paid to the possible importance of this
      symptom in social anxiety.

PMID- 12502022
TI  - A single-site, double-blind, placebo-controlled, dose-ranging study of YKP10A--a
      putative, new antidepressant.
AB  - BACKGROUND: YKP10A is a novel, new antidepressant that may affect dopamine
      neurotransmission. We present results from the first Phase II clinical trial of
      YKP10A antidepressant activity in patients with major depression. METHODS: This
      was a single-site, placebo-controlled, dose-ranging study. Patients with major
      depression were randomly assigned to one of four double-blind treatment
      conditions: YKP10A 100-300 mg/day, YKP10A 400-600 mg/day, YKP10A 700-900 mg/day,
      or placebo for 8 weeks. RESULTS: 43 patients were screened and 35 were
      randomized. Nineteen patients (54.3%) completed the entire 8-week study. Five
      YKP10A-treated patients (19%) discontinued treatment for adverse events. Thirty
      eight percent of patients in the medium dose YKP10A group had a reduction in
      baseline HAM-D17 score > or = 50% compared with the low-dose (13%), high-dose
      (13%), and placebo (29%) groups. A similar nonsignificant 'signal' for
      therapeutic activity was also seen in the medium-dose YKP10A group on the HAM-D28
      and the Montgomery-Asberg Depression Rating Scale (MADRS). Headaches,
      nervousness, agitation, insomnia, and gastrointestinal complaints were the most
      commonly reported side effects. Two cases of hypomania were observed.
      LIMITATIONS: This preliminary, single-site study was not powered to detect a
      statistically significant difference from placebo among treatment groups.
      CONCLUSION: YKP10A may have antidepressant activity at a daily dose range of 400
      600 mg.

PMID- 12502023
TI  - Differential serotonergic inhibition of in vitro striatal [3H]acetylcholine
      release in prenatally cocaine-exposed male and female rats.
AB  - Previous research indicates that prenatal cocaine (pCOC)-exposure results in
      greater 5-HT3 agonist-induced inhibition of electrically evoked [3H]acetylcholine
      (ACh) overflow in rat striatal slices. The present study examines the effects of
      fluoxetine (FLU)-induced and exogenous serotonin (5-HT) on electrically evoked
      ACh release from striatal slices prepared from adult male and female (in periods
      of diestrus or proestrus) rats exposed to saline or cocaine in utero.
      Additionally, we assessed the impact of monoaminergic receptor stimulation on
      evoked ACh release by superfusion with selective 5-HT2, 5-HT3 and D2 receptor
      antagonists in the presence of FLU-induced and exogenous 5-HT and measuring the
      capacity of these drugs to reverse inhibitory effects of 5-HT. Given our previous
      findings of accentuated inhibition of ACh release by 5-HT3 agonism in striata of
      pCOC-exposed adult rats, we hypothesized that superfusion of endogenous and
      exogenous 5-HT would lead to greater suppression of evoked ACh release in this
      group of animals. Our results indicated that ACh release from slices of all
      prenatal saline (pSAL) rats was inhibited comparably by FLU (10 microM)-elicited
      increases in endogenous 5-HT or by increases elicited with application of
      exogenous 5-HT (5 microM). Robust FLU-mediated inhibition of ACh release was
      evident in slices from pCOC male and pCOC diestrus female rats vs. their
      respective PSAL control groups. Superfusion of striatal slices with 5-HT (5
      microM) produced a pattern of ACh inhibition similar to that produced by FLU;
      however, the magnitude of ACh inhibition was consistently greater than that
      observed with FLU. Inhibition of ACh overflow by FLU was blocked by co
      superfusion with ketanserin, a 5-HT2 receptor antagonist. ICS-205,930, a 5-HT3
      receptor antagonist or sulpiride, a D2 receptor antagonist. Conversely,
      serotonergic inhibition of ACh overflow was only blocked by a high concentration
      of ICS-205,930 (5 microM) and was completely reversed by sulpiride (1 microM).
      Collectively, these findings demonstrate serotonergic modulation of cholinergic
      neurons varying as a function of prenatal treatment, sex and, for females, phase
      of estrous. Inhibition of ACh release by 5-HT appears to be mediated by a complex
      relationship between 5-HT2, 5-HT3 and D2 receptor regulation, as the blockade of
      any of these receptors reversed the inhibitory effects of FLU on ACh release.
      Conversely, in the case of exogenous 5-HT-induced inhibition, only blockade of D2
      receptors and high concentrations of the 5-HT3 receptor antagonists were capable
      of reversing monoaminergic inhibition. These data support the hypothesis that the
      enhanced serotonergic modulation of ACh neurons in pCOC-exposed animals is
      largely mediated by dopamine (DA) and reflect a major biochemical persistence of
      neurodevelopmental adaptations elicited by early cocaine exposure.

PMID- 12502024
TI  - Does risperidone act better in schizophrenic patients who have a family or
      obstetric history?
AB  - PURPOSE: The aim of the study was to assess the effect of treatment with
      risperidone on psychopathological symptoms and cognitive deficits in
      schizophrenic patients, in relation to family history, obstetric complications
      and duration of the illness. METHODS: Fifty schizophrenic inpatients (29 males,
      21 females), aged 16-50 (mean 28 years), with duration of the illness 1-15 (mean
      4 years) who successfully completed a 3-month risperidone treatment were included
      into the study. Family history of psychiatric illness and the presence of
      obstetric complications were estimated by a semistructured questionnaire.
      Schizophrenic symptoms were assessed using the Positive and Negative Symptoms
      Scale (PANSS). Cognitive abilities were measured by neuropsychological "frontal
      lobe" tests: Trail Making Test (TMT), part B, Stroop Color Word Interference
      Test, part B, and Wisconsin Card Sorting Test (WCST). The clinical and
      neuropsychological evaluation was performed before and after 3 months of
      risperidone treatment, in doses 2-6 mg (mean 4.2 mg/day). RESULTS: Before
      treatment, patients with family history had significantly higher intensity of
      negative symptoms, and obtained worse results on WCST perseverative errors (PE)
      and correct categories (CC). These measures were also impaired in subjects with
      obstetric complications. Additionally, in patients with obstetric complications,
      total and general PANSS psychopathology was higher and the results of Stroop B
      were worse. After a 3-month treatment with risperidone, no difference between
      respective groups was observed both in psychopathology and in neuropsychological
      tests. Patients with obstetric complications had higher degree of improvement on
      positive and negative symptoms and on TMT-B than the remaining ones. Patients
      with longer duration of the illness had less improvement on positive symptoms
      with risperidone treatment. CONCLUSIONS: The results of this study show that
      treatment with risperidone results in better compensation of psychopathological
      (negative symptoms) and neuropsychological (working memory) deficits in patients
      who have a family history and/or obstetric complications. This may be due to a
      favourable effect of risperidone on the prefrontal cortex dysfunction mediating
      these deficits.

PMID- 12502025
TI  - Interleukin 1alpha alters hippocampal serotonin and norepinephrine release during
      open-field behavior in Sprague-Dawley animals: differences from the Fawn-Hooded
      animal model of depression.
AB  - Detection of two biogenic amine neurotransmitters, serotonin (5-HT) and
      norepinephrine (NE) within the CA1 region of the hippocampus (HPC) of behaving
      male laboratory animals (Rattus norvegicus), was performed with miniature carbon
      sensors (BRODERICK PROBES) and in vivo semidifferential microvoltammetry after
      acute administration of the soluble immune factor, human recombinant, interleukin
      (IL) 1alpha (10 and 100 ng/kg i.p.). Two animal models were compared, i.e., (a)
      the Sprague-Dawley (SD) model, a strain neither biochemically nor immune
      challenged and (b) the Fawn-Hooded (FH) model, a biochemically (5-HT-deficient)
      and immune-challenged animal. Open-field behaviors, locomotion (ambulations) and
      stereotypy (fine movements of sniffing and grooming) were monitored with infrared
      photobeams while 5-HT and NE were selectively and separately detected within
      seconds in real time. Subchronic studies were performed in the same animals 24 h
      later at which time no further drug was administered. Results from acute
      treatment studies showed that IL-1alpha altered HPC monoamines and behavior viz-a
      viz habituation values (baseline) in the SD strain differently from those in the
      FH strain as follows: (1) although 5-HT release was significantly increased
      within CA1 region of HPC in both SD and FH strains (P<.0001), the extent of the
      HPC 5-HT increase in the 5-HT-deficient FH strain was significantly less than
      that of the SD strain at both doses (P<.0001). The subchronic studies showed that
      5-HT release within the HPC in the SD strain significantly increased (135%) over
      drug treatment values (P<.001), whereas HPC 5-HT release in the FH strain
      remained the same as that seen in the acute drug treatment studies; the
      difference between strains for the subchronic study was also statistically
      significant (P<.01). (2) IL-1alpha significantly decreased HPC NE release in the
      SD strain (P<.0004) while IL-1alpha decreased HPC NE release in the FH strain
      only at the 10-ng/kg dose (P<.001); at the 100-ng/kg dose in the FH strain, NE
      rebounded towards baseline and increased 15% above baseline reaching statistical
      significance (P<.05). Subchronic studies in the SD strain showed a further
      decreased NE signal to 38% below baseline (P<.0001), whereas subchronic studies
      in the FH strain showed a significant increase in NE release (P<.02). The
      difference between strains in the subchronic NE studies was significant (P<.001).
      (3) Ambulations were increased after IL-1alpha administration in acute studies in
      both the SD and the FH strains, but the increase did not reach statistical
      significance, whereas in the subchronic studies, both strains exhibited
      significant increases as revealed by post hoc analyses (P<.05). There was a
      statistically significant difference between strains in acute studies (P<.001),
      whereas no significant differences between models were seen in ambulation
      behavior in subchronic studies. (4) Fine movements increased over baseline after
      IL-1alpha administration in both animal models in acute studies, however, results
      did not reach statistical significance, likely due to the episodic effect of IL
      1alpha on movement behavior in both the SD and the FH strains. However, the SD
      strain showed a significant increase in fine movement behavior during the
      subchronic studies (P<.02). Significant differences in fine movements between
      animal models were not observed either acutely or in subchronic studies. In
      summary, the data show that immune modulation by IL-1alpha affects HPC
      neurochemistry and behavior in SD versus FH animal models differently and/or to
      different degrees. The data show that while the FH animal model is subsensitive
      to 5-HT agonists, 5-HT function can be stimulated. Comparison of genetically
      diverse animal models provides a reliable means to identify and discern cytokine
      induced depressive versus stressor properties. Selective sensor technology
      provides a powerful tool as movement behavior is monitored and interpreted as a
      function of monoamine neurotransmission.

PMID- 12502026
TI  - Modulation of cocaine-induced place preferences by alcohol.
AB  - Behavioral and physiological evidence suggests that alcohol modulates the effects
      produced by cocaine. To assess whether such modulation is evident with cocaine's
      affective properties, the present studies examined the effects of alcohol on
      cocaine-induced conditioned place preferences (CPP). In Experiment 1, male
      Sprague-Dawley rats were assigned to one of three groups based on whether they
      were conditioned with 20 mg/kg cocaine (Group C), 0.5 g/kg alcohol (Group A), or
      the combination (Group C/A). On the first conditioning trial, animals were
      injected with the drug(s) or vehicle and placed on one side of a place preference
      apparatus. On the next day, animals initially injected with drug received vehicle
      (and vice versa) and placed on the other side of the chamber. This cycle was
      repeated four times. Animals were then tested for their compartment preference.
      In Experiment 2, subjects were treated identically except that 1.5 g/kg alcohol
      was administered. In both experiments, Group C displayed a significant preference
      for the drug-paired compartment. Group A (in both experiments) showed no
      conditioned effect. In Experiment 1, Group C/A failed to display a significant
      preference, spending an amount of time in each compartment that was the numerical
      average of Groups C and A. In Experiment 2, the cocaine-induced preference was
      completely abated by 1.5 g/kg alcohol. These results indicate that alcohol
      produces a dose-dependent modulation of the affective properties of cocaine.

PMID- 12502027
TI  - Diurnal rhythm in extracellular levels of 5-hydroxyindoleacetic acid in the
      medial prefrontal cortex of freely moving rats: an in vivo microdialysis study.
AB  - The cerebral monoaminergic nervous system was monitored for its diurnal changes
      to find whether these can be used as neurochemical indices for emotional states.
      Freely moving rats that were not anesthetized were used: by employing an in vivo
      microdialysis technique, the levels of extracellular monoamine metabolites were
      measured. Under an alternating 12 h light and dark (LD) cycle and subsequent
      constant light (LL) condition, the extracellular 5-hydroxyindoleacetic acid (5
      HIAA) level was significantly higher in the dark phase than in the light phase in
      the medial prefrontal cortex (mPFC). However, the 5-HIAA levels in the light and
      dark phases in the striatum or hippocampus did not significantly differ. The
      homovanillic acid (HVA) level was significantly higher in the dark phase than in
      the light phase in the mPFC and striatum. These findings indicate that the
      extracellular 5-HIAA level in the mPFC has site-specific circadian rhythmicity.
      Furthermore, considering the relationship among diurnal rhythm, emotional
      disturbance and the mPFC, the site-specific diurnal rhythmicity of 5-HIAA in the
      mPFC may be a useful index in neurochemical studies on emotional states, such as
      seen in affective disorders and psychiatric diseases.

PMID- 12502028
TI  - Anxiogenic-like activity of L-655,708, a selective ligand for the benzodiazepine
      site of GABA(A) receptors which contain the alpha-5 subunit, in the elevated plus
      maze test.
AB  - GABA(A) receptor is a transmembrane hetero-oligomeric protein which consists of
      five subunits, the combination of which confers unique pharmacological properties
      to the receptor. L-655,708 is a new ligand selective for GABA(A) receptors
      containing an alpha-5 subunit. It is a partial inverse agonist that exhibits a
      100-fold higher affinity for alpha-5 containing receptors, compared with alpha-1
      containing receptors. The aim of this study was to examine the effects of L
      655,708 (0.625-5 mg/kg i.p.) on anxiety tested in the elevated plus-maze in male
      mice. A number of classical parameters were collected: (a) Open arm duration; (b)
      Closed arm duration; (c) Central platform duration; (d) Open arm frequency; (e)
      Closed arm frequency; and (f) Total number of entries in the arms. Likewise,
      different ethological measures were also obtained (rears, head-dipping [HD],
      stretched attend posture [SAP] and grooming). Mice treated with L-655,708 showed
      a marked increase in the frequency of entries and the time spent in closed arms,
      as well as a reduction in the frequency of entries and the time spent in open
      arms, as compared with the control group. Unprotected HDs were also significantly
      decreased after treatment with the drug. Overall, these results indicate that L
      655,708 could exhibit an anxiogenic-like profile in the elevated plus-maze test.
      This ligand is selective for GABA(A) receptors containing an alpha-5 subunit,
      which is mainly expressed over the hippocampal formation, a region which has been
      involved in the modulation of anxiety.

PMID- 12502029
TI  - Effects of aging on brain perfusion and serotonin-2A receptor binding in the
      normal canine brain measured with single photon emission tomography.
AB  - Normal aging is associated with a decrease in number and size of neurons, loss of
      synapses and neuronal branching and with a reduced functioning neurotransmitter
      systems, such as the serotonergic system. These structural and functional
      alterations have important impact on the behavioural, cognitive and affective
      status of the individual. With the introduction of functional brain imaging in
      veterinary medicine, the canine brain can be examined in vivo, evaluating changes
      in perfusion, metabolism and neurotransmitter systems. Since cognitive decline is
      recognised in the aging dog, it was our aim to investigate whether age related
      changes concerning cerebral perfusion and binding index of the selective 5-HT2A
      receptor ligand 123I-5-I-R91150 could be found in the canine brain. A group of
      twelve normal, aging dogs, older than 96 months, was compared to a normal
      reference group (n = 12), younger than 96 months. SPET images were obtained,
      using the radiopharmaceutical 99mTc-N,N''-1,2-ethylene-diylbis-L-cysteine
      diethylester dihydrochloride (99mTc-ECD) for evaluation of the regional perfusion
      and the selective radioligand 123I-5-I-R91150 for visualization of the 5-HT2A
      receptor. Regional decrease of cerebral blood-flow was noted in the fronto- and
      temporocortical area and in the subcortical region. Age was negatively correlated
      with perfusion in the left and right fronto-cortical region. The binding index of
      the neuroreceptor radioligand was decreased in the fronto-cortical region, with a
      significant negative correlation with age in the right fronto-cortical area. No
      correlation was found between alteration of perfusion and binding index of the
      receptor ligand, suggesting that age related perfusion differences do not
      influence the binding of this radioligand. These results suggest that age related
      effects should be considered in functional canine brain imaging.

PMID- 12502030
TI  - Normal phospholipid-related signal transduction in autism.
AB  - The aim of this study was to test the hypothesis that autism (a
      neurodevelopmental disorder of unknown etiology) is associated with altered
      phospholipid-related signal transduction using the niacin skin flush test. This
      is the first reported use of this test in this disorder. The response to topical
      aqueous methyl nicotinate solution was recorded at 5-min intervals over 20 min in
      eight patients with autism and in 16 age- and sex-matched normal individuals with
      no history of this or any other major neuropsychiatric disorder. There was no
      significant difference between the mean volumetric niacin response (VNR) (+/-
      S.E.M.) in the patients with autism, 27.0 (+/- 2.2) mol s l(-1), and the mean VNR
      of 27.6 (+/- 2.4) mol s l(-1) in the control group (P>.8). Therefore, there
      appears to be no evidence of altered phosopholipid-related signal transduction in
      autism as assessed by this test. Furthermore, since the VNR is reduced in a
      related disorder, schizophrenia, these results suggest fatty acid abnormalities
      in autism are likely to differ from those in schizophrenia.

PMID- 12502031
TI  - Liver function tests during treatment with antipsychotic drugs: a case series of
      23 patients.
AB  - Atypical antipsychotics represent a new class of medication for the treatment of
      schizophrenia and their use is associated with a reduction of neurological side
      effects. This article reports the result of the systematic clinical and
      biological supervision of hepatic enzymes on 23 schizophrenic inpatients treated
      by atypical antipsychotic during 2 weeks at Days 1 (D1), 7 (D7), and 14 (D14) in
      a naturalistic study during 6 months. The drug administrated was limited to four
      medications--risperidone, amisulpride, olanzapine, and clozapine--but other
      psychotropic agents were prescribed. Six cases of biological cytolytic hepatitis
      were observed. Due to the numerous risk factors and the frequency of "routine"
      conditions, careful supervision of the hepatic function is needed to prevent this
      kind of side effect.

PMID- 12502032
TI  - Early drop-outs, late drop-outs and completers: differences in the continuation
      phase of a clinical trial.
AB  - OBJECTIVE: The purpose of this study was to assess the differences between early
      (EDs), late drop-outs (LDs) and completers in the continuation phase of a
      clinical trial. METHODS: The authors studied 119 outpatients who were treatment
      responders in an 8-week open trial with fluoxetine 20 mg/day, and who were then
      enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus
      fluoxetine and cognitive behavior therapy (CBT). Patients were assessed using the
      Structured Clinical Interview for DSM-III-R-Axis I (SCID-Patient Edition),
      Hamilton Depression Rating Scale (HAMD-17) and the following self-rated scales:
      Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety
      Sensitivity Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the
      26-week continuation phase. We defined 'EDs' as patients who dropped out either
      at or prior to Visit 2 (which was at 2 months into the 6-month continuation
      phase); those dropping out at Visit 3 or later were defined as 'LDs' (ED < or = 2
      months and LD > 2 months). The Kruskal-Wallis and the Mann-Whitney U tests were
      used for data analysis. RESULTS: Of the 119 outpatients, 83 were completers (mean
      age: 42.1 +/- 9.0 years, 46 [55%] women, age of onset of major depressive
      disorder [MDD] = 24.3 +/- 12.5 years), 11 were EDs (mean age: 38.1 +/- 13.0
      years, 4 [36%] women, age of onset of MDD = 22.0 +/- 11.1 years) and 25 were LDs
      (mean age: 35.2 +/- 10.4 years, 12 [48%] women, age of onset of MDD = 24.6 +/-
      11.6 years). LDs were significantly younger than completers (P<.01). There was no
      significant difference in age between EDs and LDs, nor between EDs and
      completers. EDs and completers were depressed for a longer period of time
      compared to LDs (P<.05). EDs also had significantly greater overall impairment in
      social adjustment compared to completers (P<.05). CONCLUSIONS: Our data suggest
      that LDs are significantly younger than completers, although age is not a
      predictor between EDs and LDs. Further, EDs and completers are depressed for a
      longer duration than LDs, and EDs have significantly greater social impairment
      compared to completers. Our study identified some patient characteristics
      significantly associated with dropping out of a long-term clinical trial.

PMID- 12502033
TI  - Imposex still evident in eastern Australia 10 years after tributyltin
      restrictions.
AB  - A survey of imposex in Thais orbita (Neogastropoda) along the New South Wales
      (NSW) coast, Australia, found imposex was still widespread 10 years after a
      partial ban on tributyltin (TBT) based antifouling paints. Transplant experiments
      also revealed that imposex was induced in T. orbita over a period of 9 weeks in
      Sydney Harbour, NSW. A comparison of the imposex data with that collected shortly
      after the introduction of restrictions on TBT revealed a general decline in
      imposex frequency occurring at open coast sites, an exception being the site at
      South West Rocks. Sites located within harbour/bay areas did not display a
      decline in imposex frequency but a decline in the severity of imposex was
      apparent. The observed decrease in imposex values in T. orbita may reflect a
      general decrease of butyltin contamination within the coastal environment.
      However, the persistence of contamination "hotspots" within harbours and bays
      remains a concern.

PMID- 12502034
TI  - Factors affecting the distribution of benthic macrofauna in estuaries
      contaminated by urban runoff.
AB  - Contaminants derived from urban runoff have been shown to accumulate in estuarine
      sediments, reaching concentrations potentially capable of causing biological
      effects. Demonstration of effects, however, is difficult due to strong natural
      environmental gradients and the effects of past or present point-sources of
      contamination. We used multivariate methods to test two hypotheses relating to
      the effects of urban-derived contaminants on estuarine benthic communities.
      First, that patterns of distribution and abundance of benthic invertebrates in
      two urbanised estuaries would be different from those in two non-urbanised
      estuaries. Second, that the distributions of benthic invertebrates within and
      among the four estuaries would be related to those of urban-derived contaminants.
      Concentrations of contaminants were larger in estuaries with urbanised catchments
      and concentrations of Cu, Pb, Zn and DDT in some samples exceeded those at which
      biological effects may be expected to appear. Tests of differences in composition
      of benthic communities among estuaries showed that the two urban estuaries were
      not significantly different, but that they differed from both rural estuaries,
      which also differed from each other. Distributions of benthic invertebrates were
      significantly related to those of environmental variables, and were ordinated
      along axes that correlated with both natural environmental variables (nature of
      the sediment, position in estuary) and contaminants. Differences in faunas
      between the urban and non-urban estuaries were not, however, clear-cut and nor
      were relationships between faunal assemblages and environmental variables
      (including contaminants) consistent between two times of sampling.

PMID- 12502035
TI  - Histopathological biomarkers in estuarine fish species for the assessment of
      biological effects of contaminants.
AB  - The increasing emphasis on the assessment and monitoring of estuarine ecosystems
      has highlighted the need to deploy appropriate biological indices for these
      locations. Fish diseases and histopathology, with a broad range of causes, are
      increasingly being used as indicators of environmental stress since they provide
      a definite biological end-point of historical exposure. This study reports on the
      histopathological alterations observed in selected organs and tissues of three
      species of estuarine fish (Platichthys flesus, Pomatoschistus minutus and Zoarces
      viviparus), captured from four British estuaries (the Tyne, Tees, Mersey and
      Alde), differently impacted by contaminants, including PAHs. A biannual sampling
      regime was used to identify the important seasonal variations that occur in terms
      of the observed biological effects. Inflammatory lesions and hepatocellular
      fibrillar inclusions attained their highest prevalence in P. flesus captured from
      the Tyne, Tees and Mersey. The presence of pre-neoplastic and neoplastic
      toxicopathic lesions was highest in P. flesus captured from these sites, when
      compared to fish from the Aide reference site. In particular, the prevalence of
      hepatic foci of cellular alteration (up to 43.3%) and hepatocellular adenoma (up
      to 10%) were highest in P. flesus captured from the Mersey estuary. Intersex
      (ovotestis) was only recorded in male P.flesus captured from the Mersey estuary
      (up to 8.3%) and from male Z. viviparous captured from the Tyne estuary (25%).
      Pathologies associated with the gill and the kidney were also most prevalent in
      fish captured from the Tyne, Tees and Mersey estuaries. This study has
      successfully applied histopathology to an estuarine monitoring program, both for
      the recording of toxicopathic lesions in the liver and other organs, and for the
      detection of the endpoint of endocrine disruption, intersex. As such, it provides
      a powerful integrative tool for the assessment of biological effects of
      contaminants in these environments.

PMID- 12502036
TI  - Serum antibody levels against select bacterial pathogens in Atlantic bottlenose
      dolphins, Tursiops truncatus, from Beaufort NC USA and Charleston Harbor,
      Charleston, SC, USA.
AB  - Concern over the emergence of zoonotic diseases in marine organisms is growing.
      In response to this concern, this study set out to measure antibody activities
      against bacterial pathogens in Atlantic bottlenose dolphins, Tursiops truncatus,
      from the coastal estuaries of NC and SC, USA. Individuals from Charleston SC
      harbor, a heavily industrialized shipping harbor estuary, and from Beaufort NC, a
      non-shipping estuary, were examined. Purified IgG was obtained from pooled sera
      using ammonium sulfate precipitation steps and protein-G procedures, which was
      then used to generate a panel of IgG-specific monoclonal antibodies. Two of these
      antibodies, mAbs BB-10-2 (IgG1) and BB-32-2 (IgG2b), were then used to determine
      total serum IgG concentrations using a sandwich capture ELISA. Circulating IgG
      levels were variable between individuals and between the two pods. MAb BB-10-2
      was then used in an indirect ELISA to determine serum antibody activities against
      several common marine bacteria as well as the human pathogens E. coli and E. coli
      strain 0157:H7, Vibrio parahemolyticus, V. vulnificus, V. cholerae, Mycobacteria
      marinum, M. fortuitum, and M. chelonae. The highest antibody activities were
      against mycobacteria, two of which are zoonotic pathogens. Males had the highest
      antibody activities, thus suggesting low cell-mediated immunity against
      intracellular pathogens in these individuals. T-cell proliferation in response to
      Con-A, an indicator of cell-mediated immune function, was then measured in the
      Beaufort population. Males had the lowest proliferation responses, however a
      negative correlation between antibody activities and T-cell proliferation in
      individuals could not be established for either of the Mycobacteria species.
      Overall, antibody activities against all bacteria, including innocuous species
      such as V. anguillarum, V. natrigens, and M. xenopi were highly variable between
      individual dolphins and the two pods, with some animals exhibiting very high
      activities. These studies suggests that dolphin populations should be monitored
      by following the health and seroprevalence of pathogens of interest in select
      individual animals over time.

PMID- 12502037
TI  - The physics of computed radiography.
AB  - Cassette-based computed radiography (CR) systems have continued to evolve in
      parallel with integrated, instant readout digital radiography (DR) systems. The
      image quality of present day CR systems is approaching its theoretical limits but
      is significantly inferior to DR. Further improvements in CR image quality require
      improved concepts. The aim of this review is to identify the fundamental
      limitations in CR performance. This will provide a background for the development
      of new approaches to improve photostimulable phosphor CR systems. It will also
      guide research in designing better CR systems to possibly compete with DR systems
      in terms of image quality parameters such as detective quantum efficiency and yet
      maintain CR convenience in being portable and more economical.

PMID- 12502038
TI  - Penetration depth of light re-emitted by a diffusive medium: theoretical and
      experimental investigation.
AB  - The depth at which photons penetrate into a diffusive medium before being re
      emitted has been investigated with reference to a semi-infinite homogeneous
      medium illuminated by a pencil beam. By using the diffusion equation analytical
      expressions have been obtained for the probability that photons penetrate at a
      certain depth before being detected, and for the mean path length they travel
      inside each layer of the medium. Expressions have been obtained both for the cw
      and the time domain, and simple approximate scaling relationships describing the
      dependence on the scattering properties of the medium have been found. For time
      resolved measurements both the probability and the mean path length are expected
      to be independent of the distance from the light beam at which the detector is
      placed and of the absorption coefficient of the medium. The penetration depth
      increases as the time of flight increases. In contrast, for cw measurements both
      the probability and the mean path length strongly depend on the distance and
      absorption. The penetration depth increases as the distance increases or
      absorption decreases. The accuracy of the analytical expressions has been
      demonstrated by comparisons with cw experimental results. The penetration depth
      and the mean path length provide useful information, for instance, for
      measurements of tissue oxygenation and for functional imaging of muscle and
      brain. In particular, the depth reached by received photons provides overall
      information on the volume of the tissue actually investigated, while the mean
      path is strictly related to the sensitivity to local variations of absorption.

PMID- 12502039
TI  - Localization accuracy of single current dipoles from tangential components of
      auditory evoked fields.
AB  - We investigated the localization accuracy of single current dipoles from the
      tangential components of auditory evoked fields. The tangential fields were
      measured using planar gradiometers arranged in a way so as to detect two
      orthogonal field components parallel to a flat plane. Field responses to 1 kHz
      pure tones were recorded and equivalent current dipoles (ECDs) of N1m peak were
      estimated based on a locally fitted spherical conductor model. As a measure of
      localization accuracy, the standard deviation of the coordinates of the ECDs of
      N1m was obtained from repeated measurements for one subject. The estimated ECDs
      had a standard deviation of 5.5 mm and their mean location was at the
      supratemporal plane in the sylvian fissure on the MR image of the subject. In
      order to investigate the contribution of various errors to the localization
      accuracy, simulations using a sphere model and experiments using a realistically
      shaped skull phantom were performed. It was found that the background noise,
      which consisted of instrumental noise and spontaneous brain fields, was the main
      source of the errors that could explain the observed standard deviation. Further,
      the amount of systematic error was much less than the standard deviation due to
      the background noise. These results suggest that the volume currents in a non
      spherical conductor shape such as the temporal region do not produce substantial
      errors in the localization of current dipoles from tangential components of
      auditory evoked fields.

PMID- 12502040
TI  - Three-dimensional optical tomography of the premature infant brain.
AB  - For the first time, three-dimensional images of the newborn infant brain have
      been generated using measurements of transmitted light. A 32-channel time
      resolved imaging system was employed, and data were acquired using custom-made
      helmets which couple source fibres and detector bundles to the infant head.
      Images have been reconstructed using measurements of mean flight time relative to
      those acquired on a homogeneous reference phantom, and using a head-shaped 3D
      finite-element-based forward model with an external boundary constrained to match
      the measured positions of the sources and detectors. Results are presented for a
      premature infant with a cerebral haemorrhage predominantly located within the
      left ventricle. Images representing the distribution of absorption at 780 nm and
      815 nm reveal an asymmetry consistent with the haemorrhage, and corresponding
      maps of blood volume and fractional oxygen saturation are generally within
      expected physiological values.

PMID- 12502041
TI  - Transition from ventricular fibrillation to ventricular tachycardia: a simulation
      study on the role of Ca(2+)-channel blockers in human ventricular tissue.
AB  - We study the effect of blocking the L-type Ca(2+)-channel on fibrillation in
      simulations in two-dimensional (2D) isotropic sheets of ventricular tissue and in
      a three-dimensional anisotropic anatomical model of human ventricles, using a
      previously developed model of human ventricular cells. Ventricular fibrillation
      (VF) was obtained as a result of spiral wave breakup and consisted of a varying
      number of chaotically wandering wavelets activating tissue at a frequency of
      about 6.0 Hz. We show that blocking the Ca(2+)-current by 75% can convert
      ventricular fibrillation into a periodic regime with a small number of stable
      spiral waves, ranging from six in 2D sheets of 25 x 25 cm to a single spiral in
      the anatomical model of human ventricles. The dominant frequency during this
      process changed to about 10.0 Hz in the 2D simulations, but to only 5.0 Hz in the
      whole heart simulations where a single spiral wave anchored around an anatomical
      obstacle. We show that the observed effects were due to a flattening of the
      electrical restitution curve, which prevented the generation of wave breaks and
      stabilized the activation patterns.

PMID- 12502042
TI  - An energy-based beam hardening model in tomography.
AB  - As a consequence of the polychromatic x-ray source, used in micro-computer
      tomography (microCT) and in medical CT, the attenuation is no longer a linear
      function of absorber thickness. If this nonlinear beam hardening effect is not
      compensated, the reconstructed images will be corrupted by cupping artefacts. In
      this paper, a bimodal energy model for the detected energy spectrum is presented,
      which can be used for reduction of artefacts caused by beam hardening in well
      specified conditions. Based on the combination of the spectrum of the source and
      the detector efficiency, the assumption is made that there are two dominant
      energies which can describe the system. The validity of the proposed model is
      examined by fitting the model to the experimental datapoints obtained on a
      microtomograph for different materials and source voltages.

PMID- 12502043
TI  - Ultrasound cylindrical phased array for transoesophageal thermal therapy: initial
      studies.
AB  - This work was undertaken to investigate the feasibility of constructing a
      cylindrical phased array composed of 64 elements spread around the periphery (OD
      10.6 mm) for transoesophageal ultrasound thermotherapy. The underlying operating
      principle of this applicator is to rotate a plane ultrasound beam electronically.
      For this purpose, eight adjacent transducers were successively excited with
      appropriate delay times so as to generate a plane wave. The exposure direction
      was changed by exciting a different set of eight elements. For these feasibility
      studies, we used a cylindrical prototype (OD 10.6 mm) composed of 16 elementary
      transducers distributed over a quarter of the cylinder, all operating at 4.55
      MHz. The active part was mechanically reinforced by a rigid damper structure
      behind the transducers. It was shown that an ultrasound field similar to that
      emitted by a plane transducer could be generated. Ex vivo experiments on pig's
      liver demonstrated that the ultrasound beam could be accurately rotated to
      generate sector-based lesions to a suitable depth (up to 19 mm). Throughout these
      experiments, exposures lasting 20 s were delivered at an acoustic intensity of 17
      W cm(-2). By varying the power from exposure to exposure, the depth of the lesion
      at different angles could be controlled.

PMID- 12502044
TI  - A standard dosimetry procedure for 192Ir sources used for endovascular
      brachytherapy.
AB  - The experimental dosimetry of a high dose rate (HDR) 192Ir source used for the
      brachytherapy of peripheral vessels is reported. The direct determination of the
      reference air kerma rate Kr agrees, within the experimental uncertainty, with the
      results obtained by a well ionization chamber calibrated at the NIST and the
      manufacturer's certification. A highly sensitive (HS) radiochromic film (RCF),
      that presents only one active layer, was used for the source dosimetry in a water
      phantom. The adopted experimental set-up, with the source in its catheter
      positioned on the RCF plane, seems to have given better accuracy of the RCF
      optical density measurements. The agreement between the measurement of the dose
      rate constant DKr (10 mm, pi/2) and the literature data confirmed the coherence
      of the HS RCF calibration obtained by the kerma in air measurements. The RCF
      measurements supplied dosimetric information about the dose to water per
      reference air kerma rate D(r, theta)/Kr along the source transverse bisector
      axis, the radial dose function g(r) and the anisotropy function F(r, theta). The
      value D(2 mm, pi/2)/Kr = 22.4 +/- 1.2 cGy h(-1)/(microGy h(-1)) is supplied with
      a dose uncertainty that is essentially due to the indeterminacy of the source
      position in the catheter. The data of the radial and anisotropy functions have
      been compared with Monte Carlo determinations reported in the literature.

PMID- 12502045
TI  - A DICOM-RT-based toolbox for the evaluation and verification of radiotherapy
      plans.
AB  - The verification of radiotherapy plans is an essential step in the treatment
      planning process. This is especially important for highly conformal and IMRT
      plans which produce non-intuitive fluence maps and complex 3D dose distributions.
      In this work we present a DICOM (Digital Imaging and Communication in Medicine)
      based toolbox, developed for the evaluation and the verification of radiotherapy
      treatment plans. The toolbox offers the possibility of importing treatment plans
      generated with different calculation algorithms and/or different optimization
      engines and evaluating dose distributions on an independent platform. Furthermore
      the radiotherapy set-up can be exported to the BEAM Monte Carlo code system for
      dose verification. This can be done by simulating the irradiation of the patient
      CT dataset or the irradiation of a software-generated water phantom. We show the
      application of some of the functions implemented in this toolbox for the
      evaluation and verification of an IMRT treatment of the head and neck region.

PMID- 12502046
TI  - Investigation and analysis of ferrous sulfate polyvinyl alcohol (PVA) gel
      dosimeter.
AB  - Ferrous sulfate (Fe(SO4)2) PVA gels were investigated for a range of absorbed
      doses up to 20 Gy using both magnetic resonance imaging (MRI) and
      spectrophotometry to determine R1 and optical density (OD) dose responses and G
      values. It was found that R1- and OD-dose sensitivities increased with O2
      saturation or by the introduction of a freeze-thaw cycle during preparation of
      the PVA gel. The storage temperature of the Fe(SO4)2 PVA gel at -18 degrees C
      increased R1-dose sensitivity above that of gels stored at 5 degrees C. The
      addition of sucrose to the formulation was found to result in the largest
      increase in both R1- and OD-dose sensitivities. Fe(SO4)2 PVA gel with and without
      the addition of xylenol orange was demonstrated to have a G value of
      approximately 20 ions/100 eV and with sucrose approximately 24 ions/100 eV.

PMID- 12502047
TI  - Attenuation of diagnostic energy photons by polymer gel dosimeters.
AB  - Post-irradiation changes in the linear attenuation coefficient, mu, of polymer
      gel dosimeters give rise to a change which can be measured with x-ray computed
      tomography. Polymer gel dosimeters were manufactured consisting of 3% (by weight)
      acrylamide and 3% N,N'-methylene-bis-acrylamide comonomers dissolved in aqueous
      gelatin (5% gelatin by total weight and 89% de-ionized distilled water). Mu was
      measured in a collimated radiation beam of photons from an 241Am source. Density,
      rho, of polymer gel dosimeters was measured using volumetric flasks with
      capillary stoppers. The measured post-irradiation data of mu was plotted against
      the data of rho for different batches, and linear least squares fits gave r2
      values of 0.99605 and 0.99953, with P values of less than 0.001. This confirms
      that the post-irradiation change in mu is proportional to that of rho. The change
      in rho implies a change in volume regardless of the evaluation modality of the
      polymer gel dosimeter.

PMID- 12502048
TI  - Dosimetric comparison of two 90Sr/90Y sources for intravascular brachytherapy: an
      EGSnrc Monte Carlo calculation.
AB  - A new 90Sr/90Y catheter-based system, the Beta-Cath 3.5F system, was recently
      introduced into the clinic for intravascular brachytherapy. This new system has a
      smaller diameter of delivery catheter (3.5 French) compared to the original Beta
      Cath system (5 French catheter). The new source/seed (3.5F source) has a
      different design from the original (5F) source. In this paper, we report the
      EGSnrc Monte Carlo results of two-dimensional dose rate distributions in water as
      well as the TG-60 dose parameters for the new 3.5F source and the original 5F
      source. A complete set of the dosimetric data for each individual seed is
      tabulated. A detailed dosimetric comparison was carried out for the two sources.
      The comparison shows that differences between the two sources are less than 5% in
      the region of interest for intravascular brachytherapy. Higher differences (up to
      10%) are seen in the near-source region, which is mainly inside the delivery
      catheter. Based on the present calculation and comparison, we conclude that the
      new Beta-Cath 3.5F system is dosimetrically equivalent to the original Beta-Cath
      (5F) system. Therefore, clinical dosimetry and the practice of using both the
      systems can be treated similarly.

PMID- 12502049
TI  - Influence of refractive index matching on the photon diffuse reflectance.
AB  - Photon migration in a randomly inhomogeneous, highly scattering and absorbing
      semi-infinite medium with a plane boundary is considered by a Monte Carlo (MC)
      technique. The employed MC technique combines the statistical weight scheme and
      real photon paths simulation, allowing the exclusion of the energy conservation
      problem. The internal reflection of the scattered radiation on the medium
      interface is taken into account by allowing the trajectories of photon packets to
      be split into reflected and transmitted parts. The spatial photon sensitivity
      profile (SPSP), spatially resolved diffuse reflectance and angular and spatial
      photon detector weight distributions are considered in terms of Fresnel's
      reflection/refraction on the boundary of the medium. The effect of the refractive
      index match is predicted correctly by the MC method and by the diffusion
      approximation. The results demonstrate that matching of the refractive index of
      the medium significantly improves the contrast and spatial resolution of the
      spatial photon sensitivity profile (SPSP). The results of simulation of the
      spatially resolved diffuse reflectance agree well with the results predicted by
      the diffusion approximation and the experimental results reported earlier.

PMID- 12502050
TI  - Understanding the limitations of ultrasonic backscatter measurements from
      microbubble populations.
AB  - Despite over ten years of in vitro investigations of ultrasound contrast agents,
      the level of understanding of their behaviour in ultrasound fields is limited.
      Several problems associated with these investigations, particular to the nature
      of contrast agents, are discussed. Using a commercial scanner the RF normalized
      backscatter of two different contrast agents (Definity and Quantison) was
      measured at different suspension concentrations and acoustic pressures. Both
      contrast agents scattered ultrasound nonlinearly and the backscatter showed a
      dependence on acoustic pressure. In order to assess the average behaviour of the
      agents across the range of acoustic pressures and microbubble concentrations the
      experimental data were fitted to a theoretically acceptable model using nonlinear
      regression analysis. The analysis showed that both the backscatter and the
      attenuation of the Quantison suspensions displayed a higher order of dependence
      on acoustic pressure than the Definity suspensions. It was also discovered that
      Quantison microbubbles did not demonstrate uniform behaviour across the acoustic
      pressure range. At lower acoustic pressures the behaviour could not follow a
      model similar to that which predicted the behaviour at higher acoustic pressures,
      which was mainly due to the fact that free bubbles were released in a fashion
      dependent on acoustic pressure. The fact that two different populations of
      scatterers exist in the same suspensions makes the assessment of the behaviour of
      the particular agent impossible with the high concentrations that are commonly
      used. Very low concentration suspensions whereby single scattering events can be
      monitored should be more useful. In conclusion, the approach of using high
      microbubble concentrations in order to investigate the properties of ultrasonic
      contrast agents is limited in that the results of such studies cannot be used to
      understand the behaviour of single microbubbles.

PMID- 12502051
TI  - SARs for pocket-mounted mobile telephones at 835 and 1900 MHz.
AB  - Increasingly, mobile telephones are becoming pocket-sized and are being left in
      the shirt pocket with a connection to the ear for hands-free operation. We have
      considered an anatomic model of the chest and a planar phantom recommended by US
      FCC to compare the peak 1 and 10 g SARs for four typical cellular telephones, two
      each at 835 and 1900 MHz. An agreement within +/- 10% is obtained between
      calculated and experimental 1 and 10 g SARs for various separations (2-8 mm) from
      the planar phantom used to represent different thicknesses of the clothing both
      for the antenna away from or turned back towards the body. Because of the closer
      placement of the antennas relative to the body, the peak 1 and 10 g SARs are
      considerably higher (by a factor of 2-7) for pocket-mounted telephones as
      compared to the SARs obtained using a 6 mm thick plastic ear head model--a
      procedure presently accepted both in the US and Europe. This implies that a
      telephone tested for SAR compliance against the model of the head may be severely
      out of compliance if it were placed in the shirt pocket.

PMID- 12502052
TI  - When should systematic patient positioning errors in radiotherapy be corrected?
AB  - One way to reduce patient set-up errors in radiotherapy is to measure the
      position during the first N treatment fractions, and to do an unconditional
      correction of the set-up position once at the (N + 1)th fraction. This strategy
      is known as the 'no action level' protocol. The question is when to do the
      correction, i.e. what is the optimum value of N? We determine N by minimizing the
      expectation value of the total quadratic set-up error taken over all fractions. A
      central assumption that we make is that there is no time trend in the patient set
      up. The result is a simple formula for the value of N, which is proportional to
      the square root of the total number of fractions, and to the ratio of the
      execution (delivery) error and preparation error. We also provide a formula for
      cases where the measurement error is not negligible. For typical cases the
      optimum value is N = 4. Because the optimum is shallow, the exact choice of N is
      uncritical.

PMID- 12502053
TI  - The quality of drinking water from private water supplies in Aberdeenshire, UK.
AB  - The quality of private water supplies within Aberdeenshire sampled between 1992
      and 1998 was analysed with respect to the presence of total coliforms (TC),
      faecal coliforms (FC), and nitrate. Of the approximately 1750 samples analysed,
      which included multiple samples from larger supply categories, the individual
      failure rate was 41%, 30% and 15% for TC, FC and nitrate, respectively. A
      combined failure rate for these samples was 48%. Failure rates on microbiological
      grounds displayed a seasonal trend being greater during the latter half of the
      year. Although this observation is likely to be due to a combination of local and
      regional scale factors, part of the variability in failure rate was explained by
      a significant positive relationship with rainfall amount. Concentrations of
      nitrate tended to display an opposite trend with a greater number of failures
      occurring during the spring period and no relationship with rainfall was
      immediately apparent. A relatively small number of samples (< 50) failed
      simultaneously for both coliforms and nitrate suggesting that the mechanism
      responsible for the contamination differed. A similar failure rate for samples
      collected directly from the source (i.e. well) compared with those taken from the
      potable tap (usually kitchen cold water tap) suggests that it is the groundwater
      source itself that contributes much of the microbiological and nitrate
      contamination rather than a storage or supply line contamination mechanism. A
      more frequent and random sampling of category one F supplies suggested a greater
      overall failure rate, which has its own implications for deciding an appropriate
      sampling frequency.

PMID- 12502054
TI  - Optimization of metal sulphide precipitation in fluidized-bed treatment of acidic
      wastewater.
AB  - Sulphate-reducing biofilm and suspension processes were studied for treatment of
      synthetic wastewater containing sulphate, zinc and iron. With lactate
      supplemented wastewater with 170-230mg/l Zn and 58mg/l Fe, the following
      precipitation rates were obtained: 250 and 350mg/l d for Zn in fluidized-bed
      (FBR) and upflow anaerobic sludge blanket reactors, respectively, and 80mg/l d
      for Fe in both reactors with hydraulic retention time of 16h. The effluent Zn and
      Fe concentrations remained at less than 0.1 mg/l. The alkalinity produced in
      lactate oxidation increased the initial pH of 2.5-3, resulting in effluent pH of
      7.5-8.5. The highest sulphate reduction rate was over 2000 mg/l d. In terms of
      sulphate reduction, hydrogen sulphide production and effluent alkalinity, the
      start-up of the FBR with the 10% fluidization rate was superior to the FBRs with
      20-30% fluidization rates. With increased loading rates, high recycling rate
      became an advantage. After process failure caused by intentional overloading, the
      sulphate reduction partially recovered within 2 weeks. Metal precipitates in the
      reactors were predominantly FeS2, ZnS and FeS. The metal mass balance was as
      follows: 73-86% of Zn and Fe accumulated into the reactors and water level
      adjustors, 14-23% of the metals were washed out as precipitates and 0.05-0.15%
      remained as soluble metals. Biomass yield in the sulphate-reducing processes was
      0.039-0.054g dry biomass (VS or VSS) per g of lactate oxidized or 0.035-0.074g
      dry biomass per g of sulphate reduced. The results of this work demonstrate that
      the lactate supplemented sulphate-reducing processes precipitated the metals as
      sulphides and neutralized the acidity of the synthetic wastewater.

PMID- 12502055
TI  - Plasma degradation of dyes in water with contact glow discharge electrolysis.
AB  - Contact glow discharge electrolysis (CGDE) of two dyes, weak acid brilliant red B
      and weak acid flavine G, was investigated under different concentrations,
      temperature and mediums. From the variation of their concentration with the
      reaction time, it was demonstrated that the oxidation would be a first-order
      reaction. On the base line of UV spectra of solution in the degradation process,
      we deduced that two dyes underwent the oxidative degradation in CGDE. The rate
      constants, relevant coefficients and the decolorization degree were displayed
      under different conditions.

PMID- 12502056
TI  - Distribution of rare earth elements in anionic, cationic and particulate
      fractions in boreal humus-rich streams affected by acid sulphate soils.
AB  - The abundance, fractionation and physicochemical forms of rare earth elements
      (REEs) were determined in five boreal humus-rich streams (dissolved organic
      carbon, DOC = 14-40 mg/l) affected by acid sulphate soils. The sampling was
      carried out during high-water flow in autumn when the acid sulphate soils are
      extensively flushed. The analytical procedures included ion-exchange experiments
      in field and ICP-MS determination. There was a general decrease in pH (range 4.5
      6.2) and increase in the REE concentrations (La range 0.82-23 microg/l) as the
      proportion of the catchment cover of acid sulphate soils increased, explained by
      high amounts of REEs in the acidic runoff from such soils. In each stream, four
      different REE fractions were identified: (1) A cationic fraction, which is
      dominant in the REE-rich runoff from the acid sulphate soils and which is
      depleted in HREEs due to hydrochemical and/or geochemical processes, (2) an
      anionic fraction identified as humus-REE complexes, which in general is more
      abundant the higher the DOC concentrations and which also becomes increasingly
      abundant across the lanthanide series, (3) a fraction having a well-developed
      MREE enrichment, presumably consisting of colloidal REEs, and (4) a minor
      uncharacterised particle-associated fraction. The REE pool in the streams thus
      consists of several coexisting and contrasting REE species. The identification
      and quantification of such species is a prerequisite for the precise and accurate
      characterisation of the REE hydrochemistry of the streams.

PMID- 12502057
TI  - Determination of non-ionic surfactants and their biotransformation by-products
      adsorbed on alive activated sludge.
AB  - A procedure has been developed for the determination of non-ionic surfactants
      (NS) adsorbed on particles of alive and dead activated sludge. The procedure also
      enables the determination of adsorption of major biodegradation by-products:
      short-chained ethoxylates, long- and short-chained PEG. The basis of measurement
      is the determination of NS concentration in a slurry of activated sludge and in a
      solution phase. The difference between these two concentrations represents the NS
      adsorbed on activated sludge. Separation of NS and their biotransformation by
      products from samples and then on narrower fractions was performed by a
      sequential liquid-liquid extraction and precipitation with modified Dragendorff
      reagent. The indirect tensammetric technique (ITT) was applied for the final
      determination. The developed method was checked using the example of the
      treatment of the surfactant C12E10 (oxyethylated fatty alcohol) (C12E10) in the
      continuous flow activated sludge facility. No statistically significant
      accumulation of C12E10 on the alive activated sludge was detected, probably
      because of faster C12E10 fission than its adsorption. However, significant
      adsorption of the short-chained ethoxylates (including free alcohol) on the alive
      activated sludge was found, as well as statistically significant adsorption of
      long- and short-chained PEG. The adsorption of surfactant C12E10 and its
      biodegradation by-products on dead activated sludge was found to be higher than
      the species adsorption on alive activated sludge.

PMID- 12502058
TI  - The enzymology of sludge solubilisation utilising sulphate-reducing systems: the
      properties of lipases.
AB  - The first stage in the degradation and recycling of particulate organic matter is
      the solubilisation and enhanced hydrolysis of complex polymeric organic carbon
      structures associated with the sulphidogenic environment. An investigation into
      the enzymology of these processes has shown that lipase enzyme activities were
      found predominantly associated with the organic particulate matter of the sewage
      sludge. Sonication of the sludge gave an increase in enzyme activity as the
      enzymes were released into the supernatant. pH and temperature optimisation
      studies showed optima between 6.5 and 8 and 50-60 degrees C, respectively. All
      the lipase enzymes from the methanogenic bioreactors indicated extensive
      stability for at least an hour at their respective optimum temperatures and pH;
      sulphidogenic lipases reflected limited stability at these temperatures and pH
      during this time period. Though sulphate showed inhibitory properties towards
      lipases both sulphide and sulphite appeared to enhance the activity of the
      enzymes. It is argued that these sulphur species, liberated at different times
      during the sulphate reduction process, disrupt the integrity of the organic
      particulate floc by neutralising acidic components on the surface. The release of
      further entrapped enzymes from the organic particulate matter result in a
      subsequent enhancement of hydrolysis of polymeric material.

PMID- 12502059
TI  - Continuous-flow metal biosorption in a regenerable Sargassum column.
AB  - Metal biosorption behavior of raw seaweed S. filipendula in ten consecutive
      sorption-desorption cycles has been investigated in a packed-bed flow-through
      column during a continuous removal of copper from a 35mg/L aqueous solution at pH
      5. The elutant used was a 1% (w/v) CaCl2/HCl-solution at pH 3. The sorption and
      desorption was carried out for an average of 85 and 15h, respectively,
      representing more than 41 days of continuous use of the biosorbent. The weight
      loss of biomass after this time was 21.6%. The Cu-biosorption capacity of the
      biomass, based on the initial dry weight, remained relatively constant at
      approximately 38 mg Cu/g. Loss of sorption performance was indicated by a
      shortening breakthrough time and a broadening mass-transfer zone. The column
      service time, considered up to 1 mg Cu/L in the effluent, decreased continuously
      from 25.4 h for the first to 12.7 h for the last cycle. The critical bed length,
      representing the mass-transfer zone, increased almost linearly from 28 to 34cm.
      "Life-factors" for S. filipendula were found to be 0.0008h(-1) for the
      breakthrough time and 0.008cm/h for the critical bed length, using an exponential
      decay and linear fitting functions, respectively. Regeneration with CaCl2/HCl at
      pH 3 provided elution efficiencies up to 100%. Maximum concentration factors were
      determined to be in the range 16-44, a decreasing tendency was observed with an
      increasing exposure time.

PMID- 12502060
TI  - Influence of pH and TOC concentration on Cu, Zn, Cd, and Al speciation in rivers.
AB  - Dissolved ( < approximately 4 nm, dialysis in situ), colloidal ( < 0.45 microm
      filtered, minus dissolved) and particulate (total, minus < 0.45 microm filtered)
      concentrations of Cu, Zn, Cd, (Al) in eight (three) mining polluted rivers were
      determined by atomic absorption spectrometry (flame and graphite furnace). The
      metal size distribution in the rivers was compared to pH, Ca concentration,
      alkalinity, conductivity, and total organic carbon (TOC). Data plots based on the
      present and other studies also yielded information about the interrelations
      between TOC, pH and metal adsorption in rivers and lakes. Less than 10% of Cu,
      Zn, and Cd were sorbed on particles or colloids in two rivers with average pH at
      3.1 and 5.1, whereas 46%, 21%, and 21% of Cu, Zn, and Cd, respectively, occurred
      in sorbed form in six pH neutral rivers. In three pH neutral rivers, on average
      55% of Al was in colloidal form, whereas the dissolved and particulate fractions
      were 21% and 23%, respectively. Our data combined with data from similar studies
      support conclusions from other research suggesting that the percent fraction of
      metals adsorbed on particles rises steeply from almost zero to nearly 100% within
      a narrow and element specific pH range. Changes in TOC concentration seem capable
      of shifting the pH to % metal absorption curves in the order of one pH unit.

PMID- 12502061
TI  - Catalytic wet oxidation of phenol in a trickle bed reactor over a Pt/TiO2
      catalyst.
AB  - Catalytic wet oxidation of phenol was studied in a batch and a trickle bed
      reactor using 4.45% Pt/TiO2 catalyst in the temperature range 150-205 degrees C.
      Kinetic data were obtained from batch reactor studies and used to model the
      reaction kinetics for phenol disappearance and for total organic carbon
      disappearance. Trickle bed experiments were then performed to generate data from
      a heterogeneous flow reactor. Catalyst deactivation was observed in the trickle
      bed reactor, although the exact cause was not determined. Deactivation was
      observed to linearly increase with the cumulative amount of phenol that had
      passed over the catalyst bed. Trickle bed reactor modeling was performed using a
      three-phase heterogeneous model. Model parameters were determined from literature
      correlations, batch derived kinetic data, and trickle bed derived catalyst
      deactivation data. The model equations were solved using orthogonal collocations
      on finite elements. Trickle bed performance was successfully predicted using the
      batch derived kinetic model and the three-phase reactor model. Thus, using the
      kinetics determined from limited data in the batch mode, it is possible to
      predict continuous flow multiphase reactor performance.

PMID- 12502062
TI  - How effective is intermittent chlorination to control adult mussel fouling in
      cooling water systems?
AB  - Mussel control in cooling water systems is generally achieved by means of
      chlorination. Chlorine is applied continuously or intermittently, depending on
      cost and discharge criteria. In this paper, we examined whether mussels will be
      able to survive intermittent chlorination because of their ability to close their
      valves during periods of chlorination. Experiments were carried out using three
      common species of mussels: a freshwater mussel, Dreissena polymorpha, a brackish
      water mussel, Mytilopsis leucophaeata and a marine mussel, Mytilus edulis. The
      mussels were subjected to continuous or intermittent (4 h chlorination followed
      by 4 h no chlorination) chlorination at concentrations varying from 1 to 3 mg l(
      1) and their responses (lethal and sublethal) were compared to those of control
      mussels. In addition, shell valve activity of mussels was monitored using a
      Mussel-monitor. Data clearly indicate that mussels shut their valves as soon as
      chlorine is detected in the environment and open only after chlorine dosing is
      stopped. However, under continuous chlorination mussels are constrained to keep
      the shell valves shut continuously. The mussels subjected to continuous
      chlorination at 1 mg l(-1) showed 100% mortality after 588 h (D. polymorpha), 966
      h (Mytilus edulis) and 1104 h (Mytilopsis leucophaeata), while those subjected to
      intermittent chlorination at 1 mg l(-1) showed very little or no mortality during
      the same periods. Filtration rate, foot activity index and shell valve movement
      of D. polymorpha, Mytilopsis leucophaeata and Mytilus edulis decreased more than
      90% at 1 mg l(-1) chlorine residual when compared to control. However, mussels
      subjected to intermittent chlorination showed a similar reduction (about 90%) in
      filtration rate, foot activity index and shell valve movement during chlorination
      and 3% during breaks in chlorination. The data indicate that intermittent
      chlorination between 1 and 3 mg l(-1) applied at 4 h on and 4 h off cycle is
      unlikely to control biofouling if mussels are the dominant fouling organisms.

PMID- 12502063
TI  - Microbial contamination of two urban sandstone aquifers in the UK.
AB  - Development of urban groundwater has historically been constrained by concerns
      about its quality. Rising urban water tables and overabstraction from rural
      aquifers in the UK have led to a renewed interest in urban groundwater,
      particularly the possibility of finding water of acceptable quality at depth.
      This study assessed the microbial quality of groundwater collected from depth
      specific intervals over a 15-month period within the Permo-Triassic Sherwood
      Sandstone aquifers underlying the cities of Nottingham and Birmingham. Sewage
      derived bacteria (thermotolerant coliforms, faecal streptococci and sulphite
      reducing clostridia) and viruses (enteroviruses, Norwalk-like viruses, coliphage)
      were regularly detected to depths of 60 m in the unconfined sandstone and to a
      depth of 91 m in the confined sandstone. Microbial concentrations varied
      temporally and spatially but increased frequency of contamination with depth
      coincided with geological heterogeneities such as fissures and mudstone bands.
      Significantly, detection of Norwalk-like viruses and Coxsackievirus B4 in
      groundwater corresponded with seasonal variations in virus discharge to the sewer
      system. The observation of low levels of sewage-derived microbial contaminants at
      depth in the Triassic Sandstone aquifer is explained by the movement of
      infinitesimal proportions of bulk (macroscopic) groundwater flow along
      preferential pathways (e.g., fissures, bedding planes). The existence of very
      high microbial populations at source (raw sewage) and their extremely low
      detection limits at the receptor (multilevel piezometer) enable these
      statistically extreme (microscopic) flows to be traced. Rapid penetration of
      microbial contaminants into sandstone aquifers, not previously reported,
      highlights the vulnerability of sandstone aquifers to microbial contamination.

PMID- 12502064
TI  - Influence of hydraulic shock loads and TDS on the performance of large-scale
      CETPs treating textile effluents in India.
AB  - The present study relates to the influence of hydraulic shock loads and total
      dissolved solids (TDS) on the performance of three large-scale common effluent
      treatment plants (CETPs) treating textile effluents, which is generated from
      clusters of small-scale industries in the state of Rajasthan in India. Of the
      three CETPs, two having capacities 7.0 and 9.0 million liters per day (mld) are
      located in Pali and one of capacity 6.0 mld in Balotra, District Barmer.
      Wastewater from about one thousand small-scale industries is treated in these
      CETPs. The effects of hydraulic shock loads and TDS on effluent data from
      secondary clarifier for parameters biochemical oxygen demand (BOD) and suspended
      solids (SS) for CETPs at Pali, and chemical oxygen demand (COD) and SS for the
      CETP at Balotra were studied. It was observed that the effluent BOD and SS
      remained within the prescribed limits for CETP Pali at 30% increased flow rate,
      whereas effluent COD and SS at 30% increased flow rate for CETP Balotra exceeded
      the prescribed limits and the CETP could sustain 20% increased flow rate. The
      shock loading analysis revealed that CETP Balotra had reduced capacity to sustain
      shock loads by 10% as compared to CETP Pali due to the presence of high TDS
      (15,000-20,000 mg/l). High TDS interfered with the oxygen transfer necessary for
      biological metabolism, thereby affected the efficiency of activated sludge
      process. Hence, activated sludge process treating high TDS effluents are more
      sensitive to hydraulic shock loads and prone to process upsets.

PMID- 12502065
TI  - Evaluation of granular activated carbon technology for the removal of methyl
      tertiary butyl ether (MTBE) from drinking water.
AB  - This study evaluated granular activated carbons (GACs) using rapid small-scale
      column tests (RSSCTs) on methyl tert-butyl ether (MTBE) levels from 20 to 2000
      microg/L, with or without the presence of tert-butyl alcohol, benzene, toluene, p
      xylene (BTX) in two groundwater (South Lake Tahoe Utility District [Lake Tahoe,
      CA] and Arcadia Well Field [Santa Monica, CA]) and a surface water source (Lake
      Perris, CA). Direct comparison between two GACs was made for RSSCTs conducted
      with surface water from Lake Perris. The impact of natural organic matter on GAC
      performance was investigated and found to correspond with total organic carbon
      concentration in the three source waters. Significant reduction in GAC
      performance for MTBE due to competitive adsorption from soluble fuel components
      (e.g., BTX) was observed. Little or no difference in GAC usage rate or bed life
      was detected as the empty-bed contact time is changed from 10 to 20 min for
      RSSCTs conducted in the two groundwater sources, whereas the RSSCTs conducted in
      the surface water source exhibited significant increase in GAC usage rate as the
      empty-bed contact time is decreased from 20 to 10 min. This finding suggests that
      the higher NOM content of the surface water over the groundwater sources caused a
      greater competitive-adsorption effect that made more sites on the GAC to be
      unavailable to MTBE, thus decreasing its rate of adsorption and GAC performance
      for MTBE. Finally, the impact of differential influent MTBE concentration on GAC
      performance was demonstrated.

PMID- 12502066
TI  - The thermodynamic water retention capacity of solutions and gels.
AB  - The thermodynamic water retention capacity (WRC) has been defined and applied to
      different heterogeneous phase equilibria. This definition includes others known
      from the literature for testing heterogeneous systems. For the type of a real
      solution it is shown that at constant values of temperature and pressure the WRC
      is related to the difference of the chemical potential of water between the
      original state and the state after having applied a constraint. The dependence of
      WRC on concentration of a solute is predicted to be described by an e-function
      which has been experimentally confirmed in the literature.

PMID- 12502067
TI  - Modeling of bubble plume design and oxygen transfer for reservoir restoration.
AB  - A one-dimensional bubble plume model is described to predict the gaseous mass
      transfer of air bubbles into ambient water and the appropriate design criteria of
      a bubbler for a linearly stratified reservoir. The bubble plume behavior is
      governed by two dimensionless parameters: G, the strength of stratification, and
      M, the source strength (via airflow rate). Mechanical efficiency, an indicator of
      bubbler operating cost; the rate of plume entrainment flux, an indicator of
      mixing effectiveness; and the oxygen dissolution efficiency are analyzed as
      functions of G and M for different air bubble sizes to describe optimum bubbler
      design conditions. A bubble radius close to 1 mm is recommended as it favors
      higher mechanical efficiency and oxygen dissolution efficiency.

PMID- 12502068
TI  - Analysis of trihalomethanes in drinking water using headspace-SPME technique with
      gas chromatography.
AB  - In many drinking water treatment plants, the chlorination process is one of the
      main techniques used for the disinfection of water. This disinfecting treatment
      leads to the formation of trihalomethanes (THMs) such as chloroform,
      dichlorobromomethane, chlorodibromomethane and bromoform. In this study,
      headspace-solid-phase microextraction (HS-SPME, 85 microm
      carboxen/polydimethylsiloxane fiber) technique was applied for the analysis of
      THMs in drinking water. The effects of experimental parameters such as kinds of
      SPME fiber, the volume ratio of sample to headspace, the addition of salts,
      magnetic stirring, extraction temperature, extraction time and desorption time on
      the analysis were investigated. Analytical parameters such as linearity,
      repeatability and limit of detection were also evaluated. The results of THMs
      from the survey of Seongnam (Korea) drinking water samples showed that the
      highest total trihalomethane and chloroform were 24.03 and 13.34 microg/l, which
      were well within the Korean drinking water quality standard of 100 and 80
      microg/l, respectively.

PMID- 12502069
TI  - Temperature effect on microbial community of enhanced biological phosphorus
      removal system.
AB  - Microbial population dynamics to gradual temperature change in an enhanced
      biological phosphorus removal system was kinetically investigated. As the
      temperature rose from 20.0 degrees C to 30.0 degrees C, and to 35.5 degrees C,
      the predominant microbial group changed from the phosphorus-accumulating
      organisms, PAOs (47-70% of total VSS) to the glycogen-accumulating organisms (64
      75% of total VSS), and to the ordinary heterotrophs (90% of total VSS),
      respectively. Despite the species alteration, the phosphorus contents of the PAOs
      appeared to be steady within 0.182-0.308 mg/mg VSS(PAO) regardless of the
      temperature level. The initial specific phosphorus release rates, which are
      solely due to the PAOs activities, increased with the temperature from 37.5-55.9
      to 51.8-61.3, 52.0-76.9, 147.2-210.3, and 374.2-756.3 mgP/gmVSS(PAO) h, at 20.0
      degrees C, 25.0 degrees C, 30.0 degrees C, 32.5 degrees C, and 35.0 degrees C,
      respectively. On the other hand, mean initial specific phosphorus uptake rates of
      the biomass decreased as the temperature increased; however, the data implied
      that the rate of the PAOs was higher than the other two microbial groups. These
      results indicate that the PAOs are lower-range mesophiles or possibly
      psychrophiles. As the temperature rises, the portion of energy required for
      maintenance increases substantially which reduces the energy availability for
      cell reproduction; hence, the PAOs are washed out from the system.

PMID- 12502070
TI  - Eutrophication research of West Lake, Hangzhou, China: modeling under
      uncertainty.
AB  - The models such as the eutrophication ecosystem model of West Lake, Hangzhou
      (EEM), are always used to make policy decisions for eutrophication management.
      Thus it is important to know the uncertainty in the model predictions due to the
      combined effects of uncertainty in the full set of input variables, and the
      individual input parameters whose variations have the greatest effect on
      variations in model predictions. In this study, randomized methods based on Monte
      Carlo technique have been developed and applied to the model (EEM). The technique
      consists of parameter sensitivity analysis, randomly sampling from underlying
      probability distributions and multivariate regression analysis. With this
      technique, model uncertainties during modeling are clarified and their
      propagation evaluated. Results show that among the five input parameters selected
      for uncertainty analysis, the settling rate of algae SVS and water temperature
      TEM have the largest contribution to model prediction uncertainty of the model
      outputs (PC, PS and PHYT).

PMID- 12502071
TI  - Forward and backward uncertainty propagation: an oxidation ditch modelling
      example.
AB  - In the field of water technology, forward uncertainty propagation is frequently
      used, whereas backward uncertainty propagation is rarely used. In forward
      uncertainty analysis, one moves from a given (or assumed) parameter subspace
      towards the corresponding distribution of the output or objective function.
      However, in the backward uncertainty propagation, one moves in the reverse
      direction, from the distribution function towards the parameter subspace.
      Backward uncertainty propagation, which is a generalisation of parameter
      estimation error analysis, gives information essential for designing experimental
      or monitoring programmes, and for tighter bounding of parameter uncertainty
      intervals. The procedure of carrying out backward uncertainty propagation is
      illustrated in this technical note by working example for an oxidation ditch
      wastewater treatment plant. Results obtained have demonstrated that essential
      information can be achieved by carrying out backward uncertainty propagation
      analysis.

PMID- 12502072
TI  - Degradation of phenol using tyrosinase immobilized on siliceous supports.
AB  - The degradation of phenol by tyrosinase immobilized on chemically modified sodium
      aluminosilicate (NaA), calcium aluminosilicate (CaA), and silica gel was studied.
      Phenol conversion by immobilized tyrosinase ranged between approximately 15% and
      60%, depending upon the initial phenol concentration, pH, and enzyme loading.
      Tyrosinase immobilized on CaA and on NaA could be re-used repeatedly without any
      decrease in performance. However, in studies at pH 8.0, significant enzyme
      inhibition was observed, since phenol conversion was rapid for approximately 20
      min, then reached a plateau. The inhibition was reversible; activity was restored
      upon placing the immobilized enzyme in fresh substrate. Reducing the pH to 6.8
      from 8.0 led to higher conversion of phenol, and decreased the inhibition of the
      immobilized enzyme.

PMID- 12502073
TI  - Metabolism of the soil and groundwater contaminants, ethylene dibromide and
      trichloroethylene, by the tropical leguminous tree, Leuceana leucocephala.
AB  - Ethylene dibromide (EDB; dibromoethane) and trichloroethylene (TCE) are hazardous
      environmental pollutants. The use of plants to treat polluted sites and
      groundwater, termed phytoremediation, requires plants that can both effectively
      remove the pollutant as well as grow in the climatic region of the site. In this
      paper, we report that the tropical leguminous tree, Leuceana leucocephala var.
      K636, is able to take up and metabolize EDB and TCE. The plants were grown in
      sterile hydroponic solution without its symbiont, Rhizobium. EDB and TCE were
      both metabolized by the plant, as indicated by the formation of bromide ion from
      EDB and trichloroethanol from TCE. Each plant organ was independently capable of
      debromination of EDB. L. leucocephala is being used to treat perched groundwater
      as part of a remedial alternative to address an accidental EDB spill in Hawaii.
      Bromide levels of plant tissues from the trees grown in the phytoremediation
      treatment cells at the Hawaii Site were elevated, indicating uptake and
      degradation of brominated compounds in the trees. This report is the first
      evidence of a tropical tree effectively metabolizing these common organic
      pollutants.

PMID- 12502074
TI  - Assessment of recoverable forms of sulfur particles used in bioleaching of
      contaminated sediments.
AB  - The use of recoverable sulfur particles will enhance the feasibility and reduce
      the cost of bioleaching process. Three different forms of sulfur particles,
      powder, pastilles and pellets were used to study the utilization and recovery of
      sulfur, used as energy source for thiobacilli in the bioleaching process. The
      Langmuir isotherm was used to explain the adsorption equilibrium existing between
      the sorbed and suspended bacteria and the maximum adsorption capacity obtained
      from the Langmuir isotherm was utilized to determine the specific surface area of
      the sulfur particles. The specific surface area of sulfur particles was found to
      be the determining factor in the bioleaching process and not the particle size.
      The rates of pH reduction, sulfate production and metal solubilization increased
      with increasing specific surface area of the particles. The pH reduction and
      metal solubilization were significantly enhanced by the reuse of recovered sulfur
      particles. The efficiency of metal solubilization with recovered sulfur pastilles
      was comparable to that with sulfur powder. This study revealed the practicability
      of reusing the recovered sulfur pastilles in the bioleaching process.

PMID- 12502075
TI  - Risk to breeding success of fish-eating Ardeids due to persistent organic
      contaminants in Hong Kong: evidence from organochlorine compounds in eggs.
AB  - Eggs of two Ardeid species, the Little Egret (Egretta garzetta) and the Black
      crowned Night Heron (Nycticorax nycticorax), were collected from two egretries
      located in the New Territories of Hong Kong with one located near the
      internationally acclaimed wetland reserve, the Mai Po Marshes, and the other in a
      remote site (A Chau). The eggs were analysed for organochlorine (OC) compounds
      including the DDTs, PCBs, hexachlorocyclohexanes (HCHs) and the chlordanes
      (CHLs). All of the OCs under investigation were detected in the eggs of both
      species with significantly higher levels in the Little Egret (DDTs, 560-2200;
      PCBs, 270-1700; CHLs, 81-470 ng g(-1) wet weight) than the Night Heron (DDTs, 210
      1200; PCBs, 85-600; CHLs 59-75 ng g(-1) wet weight). The DDTs consisted mainly of
      DDE with levels ranging from 85% to 95% of the total. The HCHs were at about the
      same levels in both species (8.4-30 ng g(-1) wet weight). All of the OCs had
      linear concentration probability distributions on a log-normal basis which were
      used to evaluate exposure associated with these compounds as part of a
      probabilistic risk analysis. A linear dose/response relationship for the
      percentage reduction in the survival of young associated with DDE in eggs was
      developed. This probabilistic relationship was used to establish the threshold
      level (1000 ng g(-1) wet weight) at which there was a significant level of
      reduction in the survival of young above zero and the variability in DDE
      concentrations at this effect level. Using a threshold level of 1000 ng g(-1),
      the calculated Risk Quotient (RQ) had a 12.4% probability of RQ exceeding unity
      with the Night Heron, and 40.9% with the Little Egret. These results indicate
      that the DDTs in eggs would be expected to be associated with adverse effects on
      the survival of young of both species, particularly the Little Egret.

PMID- 12502076
TI  - Aqueous photodegradation of fenthion by ultraviolet B irradiation: contribution
      of singlet oxygen in photodegradation and photochemical hydrolysis.
AB  - The objective of this study was to evaluate the photodegradation of the
      organophosphorus pesticide fenthion in the environment from a human health effect
      viewpoint. The major photodegradation products of fenthion in an aqueous solution
      under UVB irradiation (280-320nm radiation) were identified as fenthion
      sulfoxide, 3-methyl-4-methylthiophenol (MMTP), dimethyl phosphorothioate and 3
      methyl-4-methylsulfinylphenol (MMSP). MMTP, dimethyl phosphorothioate and MMSP
      were discovered as novel photodegradation products of fenthion. Kinetic analysis
      of these products showed the formation of MMTP and dimethyl phosphorothioate by
      the photochemical hydrolysis of fenthion, which was accelerated under alkaline
      conditions. The former was further oxidized to MMSP. Fenthion sulfoxide was
      directly produced by the oxidative reaction of fenthion. Contribution of
      dissolved oxygen in this photooxidation was observed by replacing the air with
      nitrogen gas in the reaction system, which prevented oxidative formation of
      fenthion sulfoxide from fenthion and MMSP from MMTP. These oxidative compounds
      were also formed from fenthion in the presence of singlet oxygen (1O2) generated
      by the visible light irradiation of rose bengal solution, while 1O2 scavengers, L
      histidine and sodium azide (NaN3) inhibited this reaction. The aqueous photolysis
      mechanisms of fenthion were proposed from a kinetic photolysis experiment study
      as follows: there were two kinds of UVB photodegradation pathways of fenthion,
      one being photochemical hydrolysis of the phosphorus-O-phenyl ester to form MMTP
      and dimethyl phosphorothioate, and the other oxygenation triggered by 1O2 and
      producing fenthion sulfoxide and MMSP. Therefore, the steady photodegradation
      products of fenthion in the water environment may be fenthion sulfoxide and MMSP.

PMID- 12502077
TI  - Analysis of the nano-kinetic movement of a single DNA by a pin-fiber video scope.
AB  - The nano-kinetics movement of a single DNA molecule was visualized by a newly
      developed video-microscope system with an optical fiber, called a "pin-fiber
      video scope". The stretching and shrinking motion was clearly observed, and its
      kinetics was analyzed by numerical calculations. The new video-microscope system
      has a potential to analyze the nano-kinetics of a molecule.

PMID- 12502078
TI  - Affinity precipitation separation of DNA binding protein using block conjugate
      composed of poly(N-isopropylacrylamide) grafted double-stranded DNA and double
      stranded DNA containing a target sequence.
AB  - In this research, we synthesized a novel DNA-polymer conjugate and evaluated its
      application to an affinity precipitation separation of TATA-box binding protein
      (TBP), which is a representative general transcription factor. The conjugate was
      composed of two fractions. One was a double-stranded DNA modified by the grafting
      of poly(N-isopropylacrylamide) (PNIPAAm), which is known as a thermosensitive
      vinyl polymer. The other fraction is a native double-stranded DNA containing a
      specific base sequence (5'-TATAAA-3') called a TATA-box. These two fractions,
      which have EcoRI termini, were treated with T4 DNA ligase, and the block
      conjugate was obtained as a precipitate after two wash processes. When the
      resultant block conjugate was introduced into a sample solution containing TBP
      (0.26 microM) and bovine serum albumin (BSA) (0.39 microM), a rapid and selective
      precipitation separation of TBP under homogeneous conditions was achieved by
      controlling temperature. The purity of TBP in the precipitation fraction was
      estimated to be above 90%.

PMID- 12502079
TI  - Electron-capturing derivatization of neutral steroids for increasing sensitivity
      in liquid chromatography/negative atmospheric pressure chemical ionization-mass
      spectrometry.
AB  - Derivatization of neutral steroids for increasing sensitivity in liquid
      chromatography/negative atmospheric pressure chemical ionization-mass
      spectrometry (APCI-MS) has been examined. Under APCI conditions, gas-phase
      electrons are provided by the corona discharge and captured by electron
      affinitive compounds. In negative APCI-MS, therefore, ultrahigh sensitivity can
      be obtained by tagging neutral steroids, whose ionization efficiencies are low in
      the conventional APCI-MS, with electron-capturing moieties, such as a nitro
      group. We synthesized various boronic acid and hydrazine derivatives having
      electron-capturing moieties as derivatization reagents for 1,2-diol compounds and
      oxosteroids, respectively. Among reagents examined, those having the 2-nitro-4
      trifluoromethylphenyl moiety were most effective in increasing sensitivity. That
      is, the detection responses of the derivatives with these reagents were increased
      by several to more than 200-fold over intact steroids, where limits of detection
      were some picograms. The developed derivatization procedures were applied to
      analyses of small amounts of steroids in human plasma and gave satisfactory
      results.

PMID- 12502080
TI  - Generation of a novel monoclonal antibody against cortisol-[C-4]-bovine serum
      albumin conjugate: application to enzyme-linked immunosorbent assay for urinary
      and serum cortisol.
AB  - Measurement of cortisol levels in body fluids is important for monitoring
      pituitary gland and adrenal functions. To develop a specific and standardized
      enzyme-linked immunosorbent assay (ELISA), a novel monoclonal anti-cortisol
      antibody has been generated using a reasonably designed haptenic derivative.
      Spleen cells were prepared from the BALB/c or A/J mouse, which had repeatedly
      been immunized with a conjugate of 4-(2-carboxyethylthio)cortisol (CET) and
      bovine serum albumin, to be fused with P3/NS1/1-Ag4-1 myeloma cells. After four
      fusion experiments, one hybridoma clone secreting a practical antibody has been
      established. The resulting monoclonal antibody CS#38 (isotype gamma1, kappa)
      showed an affinity constant (K(a)) for cortisol of 1 x 10(9) M(-1) and provided a
      practical calibration curve (detection limit, 0.26 ng per assay) in a homologous
      ELISA system employing horseradish peroxidase-labeled CET as a labeled antigen.
      Cross-reactivities with related C-21 steroids were acceptably low: 11
      deoxycortisol (4.3%), cortisone (4.0%), corticosterone (1.9%), progesterone
      (1.6%), 17alpha-hydroxyprogesterone (12%), 6beta-hydroxycortisol (8.4%), and
      tetrahydrocortisol (< 0.1%). Urinary and serum cortisol levels of healthy
      volunteers were determined by this method after methylene chloride extraction to
      be 39.0 +/- 17.0 microg/day (n = 7) and 80.8 +/- 38.9 ng/mL (n = 10),
      respectively, both of which are in the reference range.

PMID- 12502081
TI  - A novel method for the assay of alpha-glucosidase inhibitory activity using a
      multi-channel oxygen sensor.
AB  - The quantification of glucose by using a multi-channel dissolved oxygen (DO)
      meter (DOX96) with immobilized glucose oxidase (GOD) and mutarotase (MUT) was
      performed. An evaluation of the inhibitory activities for alpha-glucosidase (AGH)
      by modifying our batch-type pseudo-in vivo assay system [Oki et al.; Biol Pharm.
      Bull., 2000, 232, 1084] was also performed using a DOX96. When 45 U/well GOD and
      18.75 U/well MUT were immobilized on the surface of a gelatin membrane on the
      electrodes, the response shown by the decrease percent of DO (%) obtained with 8
      electrode wells in the same row was linear with the glucose concentration up to
      3.3 mM and a correlation coefficient larger than 0.9. To estimate the AGH
      inhibitory activity, AGH-immobilized Sepharose supports in the well of a silent
      screen plate were used. The IC50 values of acarbose and 1-deoxynojirimycin, a
      medicinal inhibitor for diabetes, were 0.70 +/- 0.08 microM and 0.40 +/- 0.13
      microM, respectively, and coincided well with those by a pseudo-in vivo assay.

PMID- 12502082
TI  - Simultaneous imaging of multiple fluorescent probes in bio-cells.
AB  - In order to obtain the full spectrum from 400 to 800 nm of each pixel of a
      microscopic image, a unique spectro-imaging system was developed using an image
      slicer. The image slicer is composed of 100 photo fibers which are arranged in a
      matrix of 10 x 10 at the entrance and 100 x 1 at the exit. A line of this 100
      signals is passed through a glism and projected onto a CCD. This system was
      applied to the fluorescent imaging of bio-cells. One of the demonstrative
      examples was simultaneous measurements of the Ca2+ concentration and the pH using
      of respective fluorescent probes. An electric signal was applied to BY-2
      protoplasts and the fluorescent spectrum from 500 nm to 800 nm was measured every
      5 s. The spectrum of the BY-2 protoplasts changed in response to the electric
      signal and the Ca2+ concentration, and the pH changes could be monitored. The
      wavelength resolution was satisfactory, but the space resolution was still rough
      in comparison with the usual microscopic systems. Notwithstanding these
      conditions, we could obtain discrete data from more than several tens of sites in
      a single-cell or a chain of several cells.

PMID- 12502083
TI  - Electrochemical monitoring of glutamate release at multiple positions in a rat
      hippocampal slice.
AB  - The continuous monitoring of the distribution of glutamate (Glu), a
      neurotransmitter released at synaptic terminals, is important in terms of
      understanding the signal transfer mechanism in the brain. In this study, we
      monitored the concentration of Glu released at multiple positions in a
      hippocampal slice continuously, and obtained an approximate Glu distribution by
      using our electrochemical glutamate sensor array. After confirming our sensor's
      high sensitivity to Glu, we placed a slice on the array, and measured the
      currents at selected electrodes in the array. When we stimulated a specific
      position in the slice electrically, the glutamate concentration increased in
      different areas after several tens of seconds. The presence of glutamate receptor
      blockers suppressed these increases. This suggests that the electrical signal was
      transferred along with neurons through synapses and stimulated the Glu release.
      Our multichannel glutamate sensor should be a powerful tool to determining the
      distribution of real-time glutamate non-invasively for the studies using
      biological samples.

PMID- 12502084
TI  - Fundamental imaging properties of transillumination laser computed tomography
      based on coherent detection imaging method.
AB  - The coherent detection imaging (CDI) method uses the optical heterodyne detection
      technique. CW and single frequency lasers having long coherence lengths are used
      to exploit the maximum advantages of heterodyne detection, such as high
      directionality, selectivity and sensitivity. The CDI method based on optical
      heterodyne detection enables selective filtering of the directional coherence
      retaining emergent photons, which leads to image reconstruction from projections,
      similar to X-ray computed tomography (CT). So far we have demonstrated the
      advantages and capabilities of the measurement technique for transillumination
      optical computed tomography in biomedicine. Here, we investigate the fundamental
      imaging properties of CDI method, such as its high directionality and
      quantitativeness, with preliminary physical phantom experiments. The results show
      that the CDI method satisfies the requirements for CT reconstruction under the
      first order approximation, and enables quantitative measurements in the sense
      that the relationship between estimated and actual concentration retains a
      satisfactory linearity.

PMID- 12502085
TI  - Potentiometric PVC membrane sensor for the determination of scopolamine in some
      pharmaceutical formulations.
AB  - A novel PVC membrane electrode for the determination of scopolamine ion based on
      the formation of an ion-association complex of scopolamine with the
      phosphotungstate counter anion as an electroactive material dispersed in a PVC
      matrix is described. The sensor shows a fast, stable, near-Nenstian response for
      1 x 10(-2) mol dm(-3) to 1 x 10(-6) mol dm(-3) scopolamine at 25 degrees C over
      the pH range of 3 - 7 with a cationic slope of 54.5 +/- 0.5 mV/decade. The lower
      detection limit is 8 x 10(-7) mol dm(-3) and the response time is 15 -45 s. The
      selectivity coefficients for scopolamine relative to the number of interfering
      substances were investigated. There was negligible interference from the studied
      cations, anions, and pharmaceutical excipients. The determination of scopolamine
      in aqueous solution shows an average recovery of 100.0% and a mean relative
      standard deviation (RSD) of 1.5% at 500 microg/cm3. The direct determination of
      scopolamine in some formulations (scopolamine injection and eye drops) gave
      results that compare favorably with those obtained by the United State of
      Pharmacopoeia method. Potentiometric titration of scopolamine with sodium
      tetraphenylborate and phosphotungstic acid as a titrant was monitored with the
      developed scopolamine electrode as an end point indicator electrode.

PMID- 12502086
TI  - Electrochemical properties of Nile Blue covalently immobilized on self-assembled
      thiol-monolayer modified gold electrodes.
AB  - A monolayer of Nile Blue (NB) has been covalently immobilized on the self
      assembled thiol-monolayer modified gold electrode. Cyclic voltammograms indicated
      a stable and reverse redox process of NB bonded on the electrode surface. The
      mechanisms of redox process coupling with proton transfer were proposed. The NB
      modified electrode showed excellent electrocatalytic activity toward Nicotinamide
      adenine dinucleotide (NADH) oxidation and horseradish peroxidase (HRP) reduction.
      A hydrogen peroxide biosensor based on NB as a mediator has been demonstrated.

PMID- 12502087
TI  - Adsorption characteristics of as(III) and as(V) with titanium dioxide loaded
      Amberlite XAD-7 resin.
AB  - The adsorption characteristics of As(V) and As(III) on titanium dioxide loaded
      Amberlite XAD-7 resin have been studied. The resin was prepared by impregnation
      of Ti(OC2H5)4 followed by hydrolysis with ammonium hydroxide. Batch adsorption
      experiments were carried out as a function of the pH, shaking time and the
      concentration of As(V) and As(III) ions. The resin showed a strong adsorption for
      As(V) from pH 1 to 5 and for As(III) from pH 5 to 10. The adsorption isotherm
      data for As(V) at pH 4 fitted well to a Langmuir equation with a binding constant
      of 59 dm3 mol(-1) and a capacity constant of 0.063 mmol g(-1). The data for
      As(III) at pH 7 also fitted well to a Langmuir equation with a binding constant
      of 5.4 dm3 mol(-1) and a capacity constant of 0.13 mmol g(-1). The effect of
      diverse ions on the adsorption of arsenic was also studied. Column adsorption
      experiments showed that the adsorption of As(III) is more favorable compared to
      As(V), due to both the faster adsorption and larger capacity for As(III) than
      As(V).

PMID- 12502088
TI  - Structural control of Schiff base ligands for selective extraction of copper(II).
AB  - Structural control of Schiff base ligands for selective extraction of copper(II)
      was investigated by changing pendant arms and the distance between two imine-N
      donor atoms in ligands. Di-Schiff base ligands, N,N'-bis(2-quinolylmethylidene)
      1,2-diiminoethane (BQIE), N,N'-bis(2-pyridylmethylidene)-1,3-diimino-2,2
      dimethylpropane (BPMP) and N,N'-bis(2-quinolylmethylidene)-1,3-diimino-2,2
      dimethylpropane (BQMP), were used as complexation reagents for ion-pair
      extraction of divalent transition metal cations into nitrobenzene with picrate
      anion. The pendant arms affected the lipophilicity of ligand to nitrobenzene, due
      to their polarity. The distance between two imine-N atoms, on the contrary, was a
      factor of controlling the extraction selectivity. BQMP has both 2-quinolyl
      pendant arms and trimethylene backbone structure; use of BQMP as a complexation
      reagent led to the selective extraction of Cu2+ in the system.

PMID- 12502089
TI  - Dipolarity, hydrogen-bond basicity and hydrogen-bond acidity of aqueous
      poly(ethylene glycol) solutions.
AB  - Poly(ethylene glycol) (PEG) in water is known to alter the structure and/or state
      of water to give a different polarity from that of pure water. We determined
      using the solvatochromic comparison method the dipolarity/polarizability (pi*),
      hydrogen bond (HB) accepting basicity (beta) and HB donating acidity (alpha) of
      aqueous solutions of PEGs of variegated molecular weights at different
      concentrations in order to understand the influence of the polymer on these
      properties of water. It was observed that PEG decreases alpha for water while it
      does not change pi* and beta appreciably in the range of the molecular weight and
      compositions studied.

PMID- 12502090
TI  - Chromium(III) determination with 1,5-diphenylcarbazide based on the oxidative
      effect of chlorine radicals generated from CCl4 sonolysis in aqueous solution.
AB  - Oxidation of Cr(III) during sonication in carbonated aqueous solutions saturated
      with CCl4 leads to the quantitative formation of Cr(VI) and provides a simple and
      rapid method for spectrophotometric chromium determination with 1,5
      diphenylcarbazide. The key to this method is the production of chlorine radicals
      when aqueous solution saturated with CCl4 is exposed to ultrasonic waves of 40
      kHz. The effects of sonication period, CCl4 solution volume, acidity, and
      interferences were discussed. The time required for a single determination is
      lower than 2 min. The relative standard deviation obtained for aqueous solutions
      with 1 microg of Cr was < 2% (N = 10) and the calculated detection limit (3sigma)
      was 5 ng of Cr.

PMID- 12502091
TI  - Magnification in excess of 100-times of the microscopic photothermal lensing
      signal from solute molecules by two-color excitation with continuous-wave lasers.
AB  - A microscopic photothermal lensing measurement under two-color continuous-wave
      laser excitation was performed to investigate a signal enhancement owing to the
      transient absorption by photoexcited solute molecules in liquid solutions. An
      intensity-modulated 409 nm laser beam and an un-modulated 532 nm laser beam were
      used for excitation, and a 670 nm probe beam was used for detecting the
      modulation amplitude of thermal lensing signals generated with a microscopic
      objective lens focusing laser beams into a capillary flow cell of 0.1 mm optical
      path length. The amplitude of the modulated signal increased as the power of the
      un-modulated laser beam increased, and a 143-times magnification was observed for
      an iso-propanol solution of naphthacene having 4.6 x 10(-4) absorbance at 409 nm
      and a negligible absorbance at 532 nm. A four-level model explaining the signal
      enhancement is proposed, and an important role of the transient absorption by
      photoexcited molecules is discussed.

PMID- 12502092
TI  - HPLC determination of catecholamines based on precolumn derivatization with 6
      aminomethylphthalhydrazide followed by chemiluminescence detection.

PMID- 12502093
TI  - Effect of oxygen on the electrochemical reduction of nitroxyl radical:
      interpretation of the mechanism for a redox probe in biological systems.

PMID- 12502094
TI  - Ion chromatographic determination of total acidity in aqueous solutions.

PMID- 12502095
TI  - Determination of traces of phosphorus in steels by laser ablation/ low-pressure
      helium-ICP-MS.

PMID- 12502096
TI  - Separation and determination of process-related impurities of industrial
      chlorpyriphos by reversed-phase high-performance liquid chromatography.

PMID- 12502097
TI  - Round robin test for depth profiling of SiO2/Si multilayer.

PMID- 12502098
TI  - Crystal structure of chloro[bis(5-bromo-salicylideniminephenyl)disulfide]
      iron(III) complex.

PMID- 12502099
TI  - Crystal structure of 1,2-bis(N-methyl-2-fluorobenzoylamino)benzene.

PMID- 12502100
TI  - Crystal structure of 6,7-dimethoxy-triptycenequinone.

PMID- 12502101
TI  - Crystal structure of a complex formed from triphenylphosphine oxide and 6-chloro
      2-pyridone.

PMID- 12502102
TI  - Harmonic ultrasound: a review.
AB  - Harmonic ultrasound is a technique based on the principle of transmitting at
      frequency f and receiving at frequency 2f (or 1/2f). This technology has become
      available through the development of wide-bandwidth transducers. Microbubble
      contrast media produce a large amount of harmonic signal. Contrast harmonic
      ultrasound provides the opportunity to image patterns of high flow vasculature
      and overall perfusion. Regions of poor perfusion, including necrosis or
      infarction, can be identified with contrast harmonic ultrasound. While
      proportionately lower, tissues also produce harmonic signals. Tissue harmonic
      ultrasound sequences often improve subjective image quality compared to
      fundamental ultrasound in echocardiographic and abdominal examinations. This
      review will discuss the physical principles of harmonic ultrasound signal
      generation, medical and animal research applications, and an overview of current
      veterinary experiences.

PMID- 12502103
TI  - Magnetic resonance for evaluation of neurologic disease in 12 horses.
AB  - Magnetic resonance (MR) imaging was used as a neurodiagnostic modality in the
      assessment of 12 horses with neurologic disease localized cranial to the foramen
      magnum. This retrospective study included a mixed population of horse breeds and
      consisted of three foals and nine adult horses. MR sequences of the head and
      central nervous system of each horse were acquired. Routine MR sequences included
      transverse T1 weighted (T1wt), T2 weighted (T2wt), and proton density images.
      Additional imaging sequences were obtained on a patient-dependent basis. Eight
      neurologic related diseases were diagnosed. MRI imaging of the horse head is a
      feasible and valuable neurodiagnostic modality in the assessment of equine
      neurologic diseases.

PMID- 12502104
TI  - Technical parameters affecting image characteristics in in vivo MR microscopy of
      the mouse.
AB  - The aim of the study was to assess the effects of changing acquisition parameters
      used for high-resolution in vivo magnetic resonance (MR) microscopy on image
      quality and scan time. The head or abdomen of 11 normal and 1 glioblastoma
      bearing anesthetized BALB/c mice were imaged using a high-resolution 7.0-Tesla
      magnet. Scan parameters such as matrix size (MTX), slice thickness (ST), number
      of excitations (NEX), pulse sequence type including repetition time (TR) and echo
      time (TE), respiratory gating, and intraperitoneal contrast medium administration
      were altered to assess their actual effect on signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR) as compared to calculated effects. As expected, SNR
      increased with increasing ST or NEX and with decreasing MTX. However, although
      the empirical increase in SNR was similar to that expected for increased ST, it
      was less than that anticipated for increasing NEX or decreasing MTX. Increasing
      NEX and applying respiratory gating both increased SNR and reduced the image
      degradation associated with respiratory motion in images of the abdomen.
      Intraperitoneal contrast medium administration produced a marked increase in CNR
      in the subject with the implanted glioblastoma, suggesting that this route is
      satisfactory for the enhancement of lesions disrupting the blood-brain barrier.
      The consequence of improving image quality in terms of spatial and contrast
      resolution is increased scan time. However, the actual increase in SNR when
      altering acquisition parameters may not be as much as predicted by theory.

PMID- 12502105
TI  - Dysplasia epiphysealis hemimelica in a Boxer puppy.
AB  - A Boxer puppy had an unusual dysplastic lesion of the distal epiphysis of the
      left femur. Biopsy and CT examination were performed. A diagnosis of dysplasia
      epiphysealis hemimelica (DEH) was made. To the investigators knowledge, this
      condition has not been described before in animals. DEH is a growth disorder
      involving preferentially the medial compartment of the lower limbs, and it is
      associated with epiphyseal hypertrophy and delayed mineralization.

PMID- 12502106
TI  - Comparison of visual analog and numeric scoring scales for assessing
      intraoperative mesenteric portovenography.
AB  - A visual analog scale and a numeric scoring scale were designed for the
      assessment of dynamic intraoperative mesenteric portovenography in the dog and
      cat. Two independent observers evaluated both scoring scales for reproducibility
      (differences between observers) and repeatability (within-observer differences)
      in the assessment of 60 trial portovenograms. Agreement (interchangeability) of
      both scales was evaluated by comparing the scores obtained in the assessment of
      200 portovenograms obtained from 100 dogs and cats. There was no statistical
      difference between the two observers when scoring the same portovenogram for
      either the visual analog scale (p = .730, reproducibility coefficient = 17.85
      units) or the numeric scoring scale (scores identical, reproducibility
      coefficient = 0). There was no statistical difference, for either of the
      observers, when the same portovenogram was assessed on two separate occasions
      using the visual analog scale (observer 1, p = .35, repeatability coefficient =
      17.93 units; observer 2, p = .42, repeatability coefficient = 8.27 units) or the
      numeric scoring scale (scores given by both observers were identical,
      repeatability coefficient = 0 for both observers). The results of comparison
      between the visual analog scale and numeric scoring scale confirmed that the two
      scoring systems were not directly interchangeable. Although both scoring systems
      demonstrated good reproducibility and repeatability, the numeric scoring scale
      possessed a number of inherent deficiencies that suggested it was not the method
      of choice for the assessment of the subjective data obtained from dynamic
      intraoperative mesenteric portovenography.

PMID- 12502107
TI  - Computed tomographic appearance of osteochondritis dissecans-like lesions of the
      proximal articular surface of the proximal phalanx in a horse.
AB  - A 6-year-old Thoroughbred gelding presented with a left forelimb lameness. The
      results of lameness examination, radiography, nuclear scintigraphy, and computed
      tomography are presented. Based on the diagnostic imaging, subchondral fractures
      and osteochondritis dissecans lesions of the proximal articular surface of the
      proximal phalanx were diagnosed. A brief discussion of osteochondritis dissecans
      is presented.

PMID- 12502108
TI  - Congenital megaesophagus with hypertrophic osteopathy in a 6-year-old dog.
AB  - Congenital megaesophagus is often sufficiently debilitating to a young puppy to
      result in an owner's request for euthanasia. If medically managed, some puppies
      may develop a functional esophagus and mature normally; in others, the dilation
      may persist, but nutritional support may be sufficient to allow skeletal
      maturation. Hypertrophic osteoarthropathy or hypertrophic osteopathy is well
      recognized in many animal species. Pulmonary neoplasia is most commonly
      associated with development of the secondary bone changes, but numerous other
      causes exist. The chronic changes of hypertrophic osteopathy were identified in a
      6-year-old German Shepherd that was debilitated by persistent congenital
      megaesophagus. To the investigators' knowledge, a relationship between long-term
      esophageal dilatation and hypertrophic osteopathy has only been reported once in
      a human patient.

PMID- 12502109
TI  - Radiology corner--canine myelography.

PMID- 12502110
TI  - Radiology corner--anal sac gas appearing as an osteolytic pelvic lesion.

PMID- 12502111
TI  - Doppler measurement of splanchnic blood flow during digestion in unsedated normal
      dogs.
AB  - The purpose of this study was to measure splanchnic blood flow during digestion
      in unsedated dogs by using duplex Doppler sonography. The study population
      consisted of 12 healthy dogs. Blood flow in the cranial mesenteric artery, the
      celiac artery, and the aorta was measured before a test meal and at 20, 60, and
      90 minutes after eating. The following measurements were made or calculated:
      vessel diameter, peak systolic velocity, end diastolic velocity, mean velocity,
      resistive index, pulsatility index, and flow volume. There was a significant
      postprandial decrease in the resistive and pulsatility indices in both the
      cranial mesenteric (preprandial RI = 0.867, postprandial RI = 0.796, preprandial
      PI = 3.033, postprandial PI = 2.173) and the celiac (preprandial RI = 0.854,
      postprandial RI = 0.769, preprandial PI = 2.639, postprandial PI = 1.930)
      arteries. In both vessels the end diastolic velocity, the mean velocity, and the
      flow volume increased significantly postprandially. These changes occurred
      significantly earlier in the celiac artery than in the cranial mesenteric artery.
      The findings most likely correspond to postprandial splanchnic vasodilation.
      Doppler ultrasound provide a good methode of detecting changes in postprandial
      splanchnic blood flow in the dog.

PMID- 12502112
TI  - Ultrasonographic and clinicopathologic findings in 21 dogs with intestinal
      adenocarcinoma.
AB  - In a retrospective study of 21 dogs with intestinal adenocarcinoma, the
      signalment, clinical presentation, laboratory findings, ultrasonographic
      features, treatment, and outcome were reviewed. Anorexia (n = 16), vomiting (n =
      15), diarrhea (n = 10), and weight loss (n = 9) were the most common clinical
      signs reported. Ultrasonographic features that were evaluated included location,
      length, wall thickness, echogenicity, regional motility, layering, regional
      lymphadenopathy, and fluid accumulation proximal to the lesion site. All lesions
      were transmural and associated with complete loss of wall layering. Maximum wall
      thickening at the lesion site ranged from 7 to 17 mm (median 12 mm, mean 11.9
      mm). Most of the dogs had a lesion measuring from 23 to 63 mm in length, (median
      40 mm, mean 42 mm). Most intestinal lesions were poorly echogenic and had an
      irregular lumen. Fluid accumulation proximal to the lesion site was identified in
      17 of 21 dogs, and in 13 of 17 dogs the fluid accumulation was considered
      moderate to severe. Regional lymphadenopathy and/or nodular mesentery/omentum
      were noted in 12 of 21 dogs. The tumor was located in small intestine for 15 dogs
      and in the colon for the remaining 6 dogs. Fifteen dogs were treated by surgical
      resection of the intestinal mass. Their median survival time was 233 days. Only
      gender appeared to influence survival. Female dogs lived a median of 28 days,
      whereas male dogs lived a median of 272 days.

PMID- 12502113
TI  - Left atrial to aortic root indices using two-dimensional and M-mode
      echocardiography in cavalier King Charles spaniels with and without left atrial
      enlargement.
AB  - Two-dimensional (2-D) echocardiographic measurement of the left atrium (LA) has
      the potential to be more accurate than the standard M-mode method, because the LA
      body can be measured. We evaluated a 2-D method for measuring LA and aorta (AO)
      in a right parasternal short-axis view and compared it to the M-mode method. An
      index for LA size (LA/AO) was calculated in 166 cavalier King Charles spaniels,
      56 normal and 110 dogs with mitral regurgitation (MR) of varying degrees
      secondary to chronic valvular disease. In normal dogs, the AO-2-D and LA/AO-2-D
      did not correlate to body weight (BW) or BW2; whereas, all M-mode values and the
      LA-2-D were significantly (p < .05) related to both BW parameters. In normal
      dogs, there was no difference between M-mode and 2-D indices. For all dogs
      (normal and dogs with MR) there was an 11% bias between the M-mode and 2-D index
      with the LA/AO-2-D being higher than the LA/AO-M. The association between the
      mean and the difference of the indices demonstrated a quadratic relationship.
      Dogs with a mean LA/AO of 2.0-2.5 showed the largest difference between the two
      indices. Small values for the 2-D coefficients of variation for respiration and
      stage of diastole were found; 3.4 and 3.1%, respectively. The 2-D index is more
      sensitive to LA enlargement than the M-mode index.

PMID- 12502114
TI  - Sonographic investigations of the gastrointestinal tract of granivorous birds.
AB  - This article describes the sonographic examination of the normal gastrointestinal
      tract of granivorous birds. Preliminary tests with dead birds were performed to
      get an idea of the sonographic echotexture of the avian gastrointestinal tract.
      Later, clinically healthy seedeaters of different weights were examined
      sonographically. As equipment a convex microcurved scanner with a particularly
      small coupling surface and an adjustable frequency from 5.5-7.5 MHz was used. For
      the investigation of the gastrointestinal tract, six sonographic approaches are
      described. After a starving time of 18 hours in the granivorous birds and water
      input, the best sonographic image quality could be obtained. Using this method,
      the crop, ventriculus, intestines, and cloaca could be demonstrated
      sonographically; whereas, it was not possible to visualize the normal
      proventriculus in granivorous birds. In contrast to mammals, the different layers
      of the wall of the gastrointestinal tract could not be visualized with the
      equipment used. Motility of individual parts of the gastrointestinal tract (GI
      tract), however, could be well demonstrated.

PMID- 12502115
TI  - Ultrasound diagnosis--ultrasonographic detection of spinal malformation in a chub
      (Leuciscus cephalus L.).

PMID- 12502116
TI  - Predictors of response to radioiodine therapy in hyperthyroid cats.
AB  - The objective of this retrospective study was to evaluate hyperthyroid cats for
      pretreatment factors that would predict response to radioiodine therapy.
      Hyperthyroidism was diagnosed in 193 cats based on elevated serum thyroxine
      levels and/or elevated thyroid to salivary gland ratios on thyroid scintigraphy.
      All cats were treated with an intravenous bolus of 4 mCi of radioiodine and
      follow-up serum thyroxine levels were evaluated at 1 week and 1, 3, 6, and 12
      months post-therapy. There was a significant relationship between pretreatment
      thyroxine values and post-treatment thyroxine values at all of the follow-up time
      points (p < 0.001). There was also a relationship between thyroid to salivary
      gland technetium scan ratio results and serum thyroxine values at pretreatment
      and at 1 week post-treatment (p = 0.02, 0.005, respectively). A greater scan
      ratio was associated with higher thyroxine levels at these time points, but not
      at 1, 3, 6 or 12 months post-therapy. Ninety-eight cats pretreated with
      methimazole were analyzed for the effect of this drug on response to therapy.
      Methimazole was discontinued > or = 5 days before radioiodine therapy in 58 cats
      and < 5 days in 31 cats, in 9 cats the number of days off methimazole was
      unknown. There was no difference in response to radioiodine based upon when
      methimazole was discontinued (p = 0.70).

PMID- 12502117
TI  - Salon nails: beautiful, itchy, or infectious.

PMID- 12502118
TI  - Necrobiotic xanthogranuloma with scleroderma.
AB  - I report the case of a 68-year-old man who presented with necrobiotic
      xanthogranuloma (NXG) with concomitant scleroderma, along with the presence of
      cryoglobulins and cryofibrinogen in the blood. Autoamputation of the distal
      fingers and parts of the ears also occurred, over time, with exposure to cold
      temperatures. This is an interesting constellation of findings in this rare
      disorder that raises questions concerning its pathogenesis. A review of the
      literature is included.

PMID- 12502119
TI  - Type I cryoglobulinemia presenting as hemorrhagic crusted leg ulcers.
AB  - Cryoglobulins (CGs) are serum proteins that reversibly precipitate when the serum
      is cooled below 37 degrees C. Cryoglobulinemias are associated with a variety of
      diseases, including hematologic, autoimmune, and infectious. Isolation of CGs
      requires handling the specimen with extreme care. We describe a 70-year-old man,
      recently diagnosed with chronic lymphocytic leukemia, who developed hemorrhagic
      crusted skin ulcers on his legs that were pruritic and painful. Results of skin
      biopsies showed dilated superficial, mid-dermal and deep-dermal blood vessels
      containing pink amorphous material and red blood cells. Cryoglobulinemia was
      suspected; however, an initial search for CGs was negative. There was concern
      about suboptimal handling of the specimen, and the test was repeated. Two percent
      CGs with IgM kappa specificity were detected. This case illustrates the
      importance of the proper handling of specimens for evaluation of
      cryoglobulinemia.

PMID- 12502120
TI  - Generalized seborrheic dermatitis in an immunodeficient newborn.

PMID- 12502121
TI  - Patients with psoriasis prefer solution and foam vehicles: a quantitative
      assessment of vehicle preference.
AB  - Psoriasis patients' acceptance of the vehicles used in topical therapy
      contributes to adherence to treatment plans and outcomes, but patient preferences
      for different vehicles have not been assessed. The purpose of this study was to
      develop a quantitative measure of patient preferences for different vehicles and
      to assess these preferences. Focus group sessions were conducted of patients with
      psoriasis to determine patient perceptions of the advantages and disadvantages of
      different topical psoriasis therapies. This information was used to derive a
      vehicle preference measure to assess different topical therapies. Twenty patients
      with psoriasis sampled different topical psoriasis medications, assessed the
      effects of the vehicles on quality of life (QOL), and completed the preference
      measure for each vehicle. The focus group sessions resulted in the development of
      a 7-item preference measure. The validity of the vehicle preference measure was
      demonstrated by good correlation with patient expectations of effects on QOL and
      by test-retest reliability. The foam and solution vehicles were preferred over
      the cream, gel, and ointment vehicles (P < .01). There was no significant
      difference between preferences for daytime and nighttime application of vehicles.
      Although validated measures of adherence to topical therapy are not yet
      available, the results of this study suggest that the characteristics of solution
      and foam may favor improved adherence to topical therapy.

PMID- 12502122
TI  - Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates
      efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis.
AB  - The efficacy and safety of a new 0.5% fluorouracil topical cream were compared
      with vehicle control for the treatment of actinic keratosis (AK). Active
      treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle
      control in achieving reduction from baseline in lesion counts and lesion
      clearance. Active treatment also resulted in significantly better global
      assessments of overall improvement. Treatment was effective regardless of the
      number of baseline lesions. Although longer treatment duration correlated with
      greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new
      microsphere-based fluorouracil formulation was generally well tolerated; adverse
      events were primarily limited to facial irritation that resolved quickly after
      treatment. This new treatment provides a safe alternative to the topical
      fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment
      of AK.

PMID- 12502123
TI  - Syndecan-1 expression during postnatal tooth and oral mucosa development in rats
      aged from two days to six weeks.
AB  - Syndecans are a family of heparan sulphate proteoglycans that regulate cell
      matrix interactions that influence cell growth, proliferation and morphology. The
      aim of this study was to observe changes in the expression of Syndecan-1 in the
      developing epithelium of the rat oral mucosa and in the epithelial cell rests of
      Malassez in the developing periodontium of normal rat molars, from late crown
      development through to early eruption. Immuno-histochemistry (Syndecan-1 N-18)
      and histochemistry (Alcec Bluel were used to observe changes in the expression of
      Syndecon-1 in rats aged two to 42 days. Results indicated that during normal
      tooth development in the rat, labelling or staining of variable intensity for
      Syndecan-1 was demonstrated in the stratified oral epithelium above the stratum
      basale in the rat tongue and palate, and in ameloblasts of the developing molar
      in rats aged two to 14 days. Histochemical staining of the predentine and dentine
      layers was consistent in all specimens. Labelling or staining for Syndecan-1 was
      negative in the rat periodontal ligament, which may suggest that either Syndecan
      1 was not expressed during normal molar root development or that continued work
      is required for identification of a suitable label in rats.

PMID- 12502124
TI  - Lower incisor changes on basal bone and in relation to the lower face: combined
      growth and treatment effects in the late mixed-dentition.
AB  - This study was designed to determine and compare the ranges of combined growth
      and late mixed-dentition treatment changes in the positions of the lower
      incisors, either on basal bone or in relation to the APog line. While there was
      considerable individual variation, movements of the lower incisors in relation to
      APog were found to be related more to changes in the angulation of the APog line
      itself, than to the movements of the incisors on the basal bone. In individual
      cases in which considerable forward movement had occurred at pogonion and in
      which deep anterior overbites had been reduced, it was often found that the lower
      incisors had moved forward considerably in relation to the APog line without
      necessarily having moved forward at all on the underlying basal bone. It was
      concluded therefore that, in such cases, lower incisor movements on basal bone
      may actually occur in the opposite direction to those in relation to the APog
      line because of the complex interaction of changes occurring in the vertical and
      horizontal positions of both point A and pogonion. In these cases, it seems
      possible for the lower dentoalveolus to be passively carried forward with growth
      of the underlying basal bone, once any deep overbite has been reduced.

PMID- 12502125
TI  - Cephalometric norms for the Chinese: a compilation of existing data.
AB  - The intention of this paper is to compile Chinese cephalometric norms for a more
      objective orthodontic diagnosis of Chinese patients so that their orthodontic
      treatment may be better planned. Studies on cephalometric norms of Chinese and
      subjects of Chinese descent were reviewed. Some important studies were available
      only in the Chinese journals and they were especially procured and translated for
      this purpose. A normal range of anteroposterior apical base differences,
      concomitant nterincisal inclinations and locations, were derived from different
      Chinese groups and were tabulated. The differences between Chinese and Caucasian
      norms are discussed. A distinctive craniofacial and dental pattern of the people
      of Chinese origin was found and is reflected in the cephalometric measurements.
      Compared with Caucasian norms, Chinese norms have skeletal, dental and soft
      tissue variations. The Chinese have a shorter cranial base and a larger ANB. The
      Chinese dentition demonstrates greater bimaxillary-alveolar protrusion, with a
      decreased interincisal angle. The Chinese soft-tissue profile shows a less
      prominent nose, with a less obtuse nasolabial angle, and more protrusive lips.

PMID- 12502126
TI  - Pulp-test responses in orthodontic patients.
AB  - The diagnosis of orofacial pain is complicated in the orthodontic patient as
      treatment-induced alterations to pulpal physiology may result in altered
      responses to pulp-test stimuli. Thirty-three subjects commencing fixed
      orthodontic treatment and another 15 subjects not undergoing orthodontic
      treatment were used in this study. Cold and electrical stimuli were applied to
      the maxillary incisor teeth prior to treatment, after the placement of fixed
      appliances and at regular intervals for both groups for up to 252 days. At
      baseline, response thresholds to electric testing were typically higher for
      orthodontic subjects, particularly for the lateral incisors. For the non
      orthodontic group, the response threshold over the 252 days was relatively
      constant. For the orthodontic group, application of force immediately increased
      the response threshold to electric pulp testing, which peaked after two months.
      By day 252, response means for lateral incisors still remained elevated.
      Responses to thermal testing were more consistent and reliable. The results of
      this study indicate that dental practitioners should interpret responses to
      electric pulp testing cautiously in orthodontic patients and that thermal testing
      with carbon dioxide snow may be more reliable.

PMID- 12502127
TI  - Uprighting of impacted lower third molars using brass ligature wire.
AB  - As the orthodontic stage at the time of the eruption of the third molar is
      usually the retention period, it is desirable for both the patient and the
      clinician that impacted or inclined third molars be uprighted without an
      appliance. Impacted lower third molars can be successfully uprighted using only
      brass ligature wire. This paper suggests that brass ligature-wire therapy can be
      used to upright impacted molars that show considerable inclination.

PMID- 12502128
TI  - Temporary tongue thrust: failure during orthodontic treatment.
AB  - This report presents the case of a 25-year-old male patient who sought
      orthodontic treatment. Oral examination revealed an Angle Class I relation, with
      a bimaxillary dento-alveolar protrusion, evidence of anterior crowding, and a
      large overbite and overjet. Radiographic examination revealed a skeletal Class I
      occlusion. During the distal movement of the canines, occlusal interferences
      between the canines occurred and the commencement of a tongue thrust was
      observed. After correction of the applied forces, the canine movement was
      completed and the habit was no longer detectable. The incident indicates that an
      unusual oral habit suspiciously occurring during treatment should lead to an
      immediate reconsideration of the orthodontic treatment strategy.

PMID- 12502129
TI  - Incomplete unilateral cleft of the primary palate: delayed secondary bone
      grafting combined with orthodontic treatment.
AB  - The presence of a fissural lateral incisor in an alveolar cleft is not a common
      occurrence and, if one is present, must in most instances be removed because of
      microdontia or because it may compromise a bone graft. This case report presents
      an example of bone grafting carried out late in the secondary stage of the
      patient's dentition, in conjunction with retention of the fissural lateral
      incisor as requested by the patient, and shows an acceptable outcome from the
      points of view of both aesthetics and dento-alveolar health.

PMID- 12502130
TI  - Laser irradiation inhibition of open gingival embrasure space after orthodontic
      treatment.
AB  - The purpose of this study was to investigate the inhibitory effect of low-energy
      laser irradiation on an incidence of open gingival embrasure space after
      orthodontic treatment. The patient was a 20-year, 7-month-old Japanese female
      with an Angle Class I malocclusion and crowding in the mandible. Treatment
      consisted of extraction of maxillary and mandibular first premolars and use of
      the Edgewise technique. A Ga-Al-As diode laser was used to irradiate an area of
      0.5 cm2 at the labial and lingual gingival papilla between the canines. The time
      of exposure was 6 minutes for 3 days, carried out between the relevelling and en
      masse stages of movement. The total energy corresponding to 6 minutes of exposure
      varied from 1.90 J/cm2. There was no further evidence of open gingival embrasure
      space, except at the mandibular central incisor. Further: an improvement in the
      gingival inflammation caused by a periodontal disease was observed, and
      periodontal pocket depth was maintained. These results suggest that low-energy
      laser irradiation may inhibit the incidence of open gingival embrasure space
      after orthodontic treatment.

PMID- 12502131
TI  - Permanent retention in the average juvenile male Australian patient.

PMID- 12502132
TI  - The Sam Bulkley Rocky Mountain Travelling Fellowship report.
AB  - The Sam Bulkley Rocky Mountain Travelling Fellowship afforded me a wonderful
      opportunity to study and to be involved at the cutting-edge of orthodontic
      treatment, especially in the treatment of aesthetically and functionally
      disadvantaged members of our community. I would like to thank everyone
      responsible for making this award possible, and also to thank all the clinicians,
      researchers and their staff who welcomed me and educated me during my visit. It
      has been most beneficial and rewarding.

PMID- 12502133
TI  - Resources for healthcare in developing countries: is user fees the answer?

PMID- 12502134
TI  - Understanding and managing breast cancer: quo vadis?

PMID- 12502135
TI  - Out-of-pocket expenditure on healthcare in a north Indian village.
AB  - BACKGROUND: Information on healthcare expenditure at the family or household
      level is important for the planning and management of health services. It is
      particularly relevant for health insurance agencies to estimate the amount of
      premium for initiating a universal health insurance system. METHODS: Of 800
      families in a village, 160 were selected by systematic random sampling. Of these,
      156 families were followed up for a period of 12 months (September 1998 to August
      1999) by making monthly visits. Responses from each family, as given by the head
      of the family, were recorded with the help of an interview schedule administered
      in the local language. The interview schedule covered any morbidity among the
      family members in the past one month and the out-of-pocket expenditure incurred
      on the same. RESULTS: The private health sector was utilized in 59.4% of total
      episodes. Utilization of the private sector was directly associated with a higher
      socioeconomic status (p = 0.002). Of the total expenditure on non-hospitalized
      cases, 83.6% was incurred in the private sector. The mean per capita annual out
      of-pocket expenditure on health was Rs 131. The median expenditure per episode
      was Rs 15. CONCLUSION: Our study shows that out-of-pocket expenditure is more
      than the government expenditure on health. There is a need for systems such as
      health insurance to protect the poor from high medical costs.

PMID- 12502136
TI  - Prevalence of asthma in urban and rural children in Tamil Nadu.
AB  - BACKGROUND: There are very few community-based studies on the prevalence of
      asthma in Indian children. We aimed to estimate the prevalence of asthma in
      children under 12 years of age and to study possible differences in the
      prevalence of childhood asthma in urban and rural areas of Tamil Nadu. METHODS: A
      total of 584 children from Chennai and 271 children from 25 villages around
      Chennai formed the urban and rural groups, respectively. From November 1999 to
      February 2000, data were collected using a simplified version of the ISAAC
      questionnaire, which was administered by trained students. Symptoms suggestive of
      asthma or hyperreactive airways disease in children under 12 years of age were
      recorded from the selected urban and rural populations by questioning the
      parents. The results were analysed separately for children 0-5 and 6-12 years of
      age. RESULTS: Of the 855 children studied, the overall prevalence of breathing
      difficulty (including asthma) was 18% and the prevalence of 'diagnosed' asthma
      was 5%. Twenty-two per cent of urban and 9% of rural children 6-12 years of age
      reported breathing difficulty 'at any time in the past' (p < 0.01). A
      significantly higher proportion of 6-12-year-old urban children also reported
      nocturnal drycough (28.4% v. 18.7%, p < 0.05). Urban children reported recent
      wheeze more often than rural children (92% v. 77%, p = 0.01). CONCLUSIONS:
      Symptoms suggestive of asthma were present in 18% of children under 12 years of
      age. Though the prevalence of diagnosed childhood asthma was about 5% in both
      urban and rural areas, the prevalence of 'breathing difficulty' and nocturnal
      cough was significantly higher among urban children in the age group of 6-12
      years. Children living in urban areas also reported 'recent wheeze' more often
      than rural children. Our data suggest that the actual prevalence of asthma and
      other 'wheezy' illnesses may be higher than that previously documented. Further
      studies are needed to confirm the difference in prevalence between urban and
      rural children and also to identify possible causes that could account for the
      higher urban prevalence of asthma in Tamil Nadu.

PMID- 12502137
TI  - Detection of day blood filarial antigens by Og4C3 ELISA test using filter paper
      samples.
AB  - BACKGROUND: The launching of the global filariasis elimination programme has
      necessitated the use of highly sensitive and specific diagnostic tests. The Og4C3
      monoclonal antibody-based ELISA test has been found to be highly specific and
      sensitive for the diagnosis of filariasis using night blood samples. However, it
      requires a serum sample which poses problems of transport and storage. Collection
      of blood samples on filter paper the will greatly circumvent these problems.
      Therefore, we evaluated the utility of the Og4C3 assay on filter paper samples
      collected during daytime. METHODS: Blood samples were collected from 63
      microfilariae (mf) carriers during different time periods in a day on filter
      paper discs as well as venous blood for sera. The mf carriers and chronic
      (hydrocele n = 20; lymphoedema n = 120) and acute filariasis (adenolymphangitis n
      = 39) patients were from the endemic areas and the non-endemic normals were from
      Uthagamandalam district of Tamil Nadu, India. The filarial antigens in the
      samples were determined using the Og4C3 filarial antigen assay as per the
      manufacturer's instructions (JCU TrapBio, Australia). The sensitivity of the
      assay on sera and filter paper samples collected during night and also on filter
      paper samples collected during different time intervals of the day were compared
      with those of the membrane filtration technique, which was used as a gold
      standard. RESULTS: The geometric mean titre of the sera samples collected during
      night was 11 units/ml for non-endemic normals and 601.2 units/ml for mf carriers.
      The specificity of the assay on sera samples collected during night was 100% and
      the sensitivity 96.8% and the positive and negative values were 100% and 95.2%,
      respectively. The antigen positivity of the filter paper samples collected during
      morning hours was 93.3% while it was 76.6% and 86.7% for afternoon and evening
      hours. A significant association was observed between antigenaemia levels and mf
      density in the blood samples collected during the night. CONCLUSION: The samples
      collected on filter paper during the day can be used as an alternative to sera
      samples for detection of filarial antigens employing Og4C3 ELISA. Also, samples
      collected during morning hours yield a higher positivity. The assay when applied
      to serum samples will be useful especially when quantitative results are
      required.

PMID- 12502138
TI  - Vaccination for hepatitis A virus is not required for patients with chronic liver
      disease in India.
AB  - BACKGROUND: Hepatitis A virus (HAV) vaccination is recommended worldwide for
      patients with chronic liver disease to prevent decompensation due to
      superinfection with HAV. India being endemic for HAV, the prevalence of pre
      existing antibodies against HAV due to subclinical exposure to the virus in
      childhood among patients with chronic liver disease may be high and, therefore,
      vaccination may not be needed. However, data are lacking on the prevalence of HAV
      antibody among patients with chronic liver disease in India. METHODS: Two hundred
      fifty-four patients attending the Liver Clinic at the All India Institute of
      Medical Sciences, New Delhi during the past 5 years and diagnosed to have either
      chronic hepatitis due to the hepatitis B virus (n = 76), hepatitis C virus (n =
      84) or cirrhosis of the liver due to the hepatitis B (n = 47) or C (n = 47) virus
      were tested for the presence of IgG anti-HAV antibody in their sera (using a
      commercial ELISA kit). RESULTS: Two hundred forty-eight (97.6%) patients tested
      positive for IgG anti-HAV. The prevalence of anti-HAV positivity was similar
      among patients with chronic hepatitis B (74, 97.4%), chronic hepatitis C (82,
      97.6%), cirrhosis of the liver due to the hepatitis B (46, 97.8%) and hepatitis C
      (46, 97.8%) virus. CONCLUSION: Vaccination against HAV is not required among
      patients with chronic liver disease in India as there is a very high prevalence
      of pre-existing antibodies in these patients.

PMID- 12502139
TI  - Non-invasive ventilation: current status.
AB  - Mechanical ventilation is being increasingly used in many disciplines by
      specialists who manage critically ill patients. Non-invasive ventilation (NIV)
      refers to the method of providing assisted ventilation without endotracheal
      intubation. This technique requires a positive-pressure ventilator, connected by
      a tubing to an interface device that directs intermittent positive pressure
      through the upper airway and actively assists ventilation. The use of NIV is
      increasing for patients with acute and chronic respiratory failure, because of
      its convenience, lower cost and minimal complications. The greatest advantage of
      NIV is that endotracheal intubation is not required. Although it is an extremely
      useful technique, it cannot be used in all patients and correct patient selection
      is important. It has been extensively used in patients with chronic obstructive
      pulmonary disease with acute or acute-on-chronic respiratory failure. It has also
      been found to be useful in acute respiratory distress syndrome, acute cardiogenic
      pulmonary oedema and acute severe asthma. All patients with respiratory failure
      need to be considered for NIV if they fulfil the requisite criteria. Patients who
      are unable to protect the upper airway, those with severe life-threatening
      hypoxaemia, or major associated organ dysfunction are unlikely to benefit from
      this technique. Despite these limitations, NIV can be useful in many conditions
      that lead to respiratory failure. NIV is a relatively new technique and has not
      found a place in all intensive care units. It is expected that this modality will
      be used more frequently in the near future.

PMID- 12502141
TI  - Neoadjuvant chemotherapy in the management of resectable oesophageal cancer.

PMID- 12502140
TI  - Cellular phones and their hazards: the current evidence.
AB  - The past decade has seen an exponential increase globally in the use of cellular
      phones (popularly known as mobile or cell phones). These phones are convenient
      and trendy. Discarding the wire means that the communication is through
      electromagnetic waves, which could have potential hazards. Alarmist reports in
      the lay press and high profile lawsuits, particularly in the West, have attracted
      attention to the possible harmful effects of cellular phones. Adverse effects
      investigated by various clinical trials include the possible link to increased
      risk of vehicular accidents, leukaemias, sleep disturbances and the more serious
      brain tumours. Available level II evidence suggests that the only proven side
      effect is an increased risk of vehicular accidents. So far, all studies have
      consistently negated any association between cellular phones and brain tumours.
      Yet, the final word remains to be said.

PMID- 12502142
TI  - Zinc supplementation: time for public health intervention.

PMID- 12502143
TI  - Surgical training in India.

PMID- 12502144
TI  - Himalayan Institute of Medical Sciences, Dehradun.

PMID- 12502145
TI  - Mountain sickness.

PMID- 12502146
TI  - None so blind as those who will not see.

PMID- 12502147
TI  - An inexpensive technique for making Barron bands for ligation of haemorrhoids.

PMID- 12502148
TI  - Effectiveness of training on the knowledge of HIV/AIDS among nurses in Delhi.

PMID- 12502149
TI  - STI-571 (Gleevec) in the treatment of chronic myeloid leukaemia.

PMID- 12502150
TI  - Cortisol levels following therapy in tuberculous Addison's disease: results of
      long term follow up.

PMID- 12502151
TI  - An epidemiological and experimental study of dracontiasis in Chitaldrug District.
      1932.

PMID- 12502152
TI  - A biological method for the control of dracontiasis. 1936.

PMID- 12502153
TI  - Why better operators receive worse warnings.
AB  - Descriptions of a dynamic warning system usually assign the system certain
      diagnostic values. Operators should adjust their responses to these values when
      considering the output of the system for their decisions. This approach is not
      necessarily appropriate for complex systems that are controlled by human
      operators. Here the operators' actions are likely to change the frequency of
      events that should trigger a warning. Consequently the operator will change the
      predictive value of a warning system that is imperfectly correlated with the
      monitored events. In general its diagnostic value decreases for better operators.
      This phenomenon is demonstrated on the example of binary warnings about binary
      events, and an empirical demonstration of the phenomenon is provided in an
      experimental study of a process control task. Actual or potential applications of
      this research include improved understanding of the determinants of operators'
      responses to warnings, which should help in the design of better warning systems.

PMID- 12502154
TI  - Learning to use a home medical device: mediating age-related differences with
      training.
AB  - We examined the differential benefits of instructional materials for younger and
      older adults learning to use a home medical device. Participants received
      training on use of a blood glucose meter via either a user manual (a text guide
      with pictures) or an instructional video. Performance was measured immediately
      and then after a 2-week retention interval. Type of instruction was critical for
      determining older adults' performance. Older adults trained using the manual had
      poorer performance than did all other groups. After only 1 calibration, older
      adults who received video training performed as accurately as did the younger
      adults. Older adults' performance was more influenced by the retention interval;
      however, the benefit of the video training was maintained for the older adults
      across the retention interval. Confidence ratings paralleled subjective workload
      ratings. The data provide practical information to guide the development of
      training programs for systems that will be used by both younger and older adults;
      they also demonstrate the need for age-related usability testing even for
      training program design.

PMID- 12502155
TI  - Malleable attentional resources theory: a new explanation for the effects of
      mental underload on performance.
AB  - This paper proposes a new theory to account for the effects of underload on
      performance. Malleable attentional resources theory posits that attentional
      capacity can change size in response to changes in task demands. As such, the
      performance decrements associated with mental underload can be explained by a
      lack of appropriate attentional resources. These proposals were explored in a
      driving simulator experiment. Vehicle automation was manipulated at 4 levels, and
      mental workload was assessed with a secondary task. Eye movements were also
      recorded to determine whether attentional capacity varied with mental workload.
      The results showed a clear decrease in mental workload associated with some
      levels of automation. Most striking, though, were the results derived from the
      eye movement recordings, which demonstrated that attentional capacity varies
      directly with level of mental workload. These data fully supported the
      predictions of the new theory. Malleable attentional resources theory suggests
      that future vehicle designers should employ their technology in driver support
      systems rather than in automation to replace the driver. The implications of this
      theory are discussed with regard to capacity models of attention as well as to
      the design of future vehicle systems.

PMID- 12502156
TI  - A sociotechnical method for designing work systems.
AB  - The paper describes a new method for allocating work between and among humans and
      machines. The method consists of a series of stages, which cover how the overall
      work system should be organized and designed; how tasks within the work system
      should be allocated (human-human allocations); and how tasks involving the use of
      technology should be allocated (human-machine allocations). The method makes use
      of a series of decision criteria that allow end users to consider a range of
      factors relevant to function allocation, including aspects of job,
      organizational, and technological design. The method is described in detail using
      an example drawn from a workshop involving the redesign of a naval command and
      control (C2) subsystem. We also report preliminary details of the evaluation of
      the method, based on the views of participants at the workshop. A final section
      outlines the contribution of the work in terms of current theoretical
      developments within the domain of function allocation. The method has been
      applied to the domain of naval C2 systems; however, it is also designed for
      generic use within function allocation and sociotechnical work systems.

PMID- 12502157
TI  - The effect of typing posture on wrist extensor muscle loading.
AB  - High static loading of the forearm extensor musculature has been observed during
      keying tasks. To reduce the level of loading, one must first understand the
      contributing factors. A simulation of the human finger was used to determine
      muscle force contributions during a static index finger key press at several
      wrist postures. The planar model included active and passive muscle forces of the
      intrinsic and extrinsic finger muscles. The model was expanded to include the
      passive forces from the other fingers as well as the weight of the hand to
      determine the exertion required of the wrist extensor muscles to maintain the
      given wrist and finger postures. Model results indicated that greater than 25% of
      maximal exertion is required of the wrist extensors when the wrist is extended to
      30. The increased moment contribution from passive forces of the extrinsic finger
      flexor muscles was responsible for the majority of the increased wrist extensor
      contribution as the wrist was extended. These findings are in relative agreement
      with previous electromyographic studies and may indicate a mechanism for forearm
      extensor pain in office workers. Potential applications of this research include
      ergonomic modeling of the upper limb to determine internal loads that may lead to
      work-related disorders.

PMID- 12502158
TI  - Aiding planning in air traffic control: an experimental investigation of the
      effects of perceptual information integration.
AB  - Prior research examined how controllers plan in their traditional environment and
      identified various information uncertainties as detriments to planning. A
      planning aid was designed to reduce this uncertainty by perceptually representing
      important constraints. This included integrating spatial information on the radar
      screen with discrete information (planned sequences of air traffic). Previous
      research reported improved planning performance and decreased workload in the
      planning aid condition. The purpose of this paper was to determine the source of
      these performance improvements. Analysis of computer interactions using log
      linear modeling showed that the planning interface led to less repetitive--but
      more integrated--information retrieval compared with the traditional planning
      environment. Ecological interface design principles helped explain how the
      integrated information retrieval gave rise to the performance improvements.
      Actual or potential applications of this research include the design and
      evaluation of interface automation that keeps users in active control by
      modification of perceptual task characteristics.

PMID- 12502159
TI  - Using tactile features to help functionally blind individuals denominate
      banknotes.
AB  - This study, which was conducted for the Bank of Canada, assessed the feasibility
      of presenting a raised texture feature together with a tactile denomination code
      on the next Canadian banknote series ($5, $10, $20, $50, and $100). Adding
      information accessible by hand would permit functionally blind individuals to
      independently denominate banknotes. In Experiment 1, 20 blindfolded, sighted
      university students denominated a set of 8 alternate tactile feature designs.
      Across the 8 design series, the proportion of correct responses never fell below
      .97; the mean response time per banknote ranged from 11.4 to 13.1 s. In
      Experiment 2, 27 functionally blind participants denominated 4 of the previous 8
      candidate sets of banknotes. The proportion of correct responses never fell below
      .92; the corresponding mean response time per banknote ranged from 11.7 to 13.0
      s. The Bank of Canada selected one of the four raised-texture designs for
      inclusion on its new banknote series. Other potential applications include
      designing haptic displays for teleoperation and virtual environment systems.

PMID- 12502160
TI  - Dimensions of arousal: wakefulness and vigor.
AB  - Factors such as shift work, sleep deprivation, and noise affect job performance
      in part because they affect individuals' levels of arousal. Recent work on
      arousal has identified two distinct forms of arousal that affect performance in
      very different ways. Tense arousal represents a continuum from calmness to
      anxiety, whereas energetic arousal reflects a continuum from tiredness to energy.
      The three studies reported here sought to determine the usefulness of breaking
      down energetic arousal still further, into dimensions of wakefulness and vigor.
      In the first study, a factor analysis of self-reported psychological state data
      determined that wakefulness and vigor did form separate factors. The second study
      found that the circadian rhythms of wakefulness and vigor differed; wakefulness
      increased over the day, whereas vigor peaked at noon. The third study examined
      the relationship between the two types of arousal and performance on a reading
      comprehension task. Although both wakefulness and vigor showed an association
      with performance, only vigor showed the inverted-U-shaped relationship embodied
      in the Yerkes-Dodson law. These data suggest that distinguishing between
      wakefulness and vigor will clarify how changes in arousal levels affect
      productivity. These results also suggest that the schedule for optimal
      performance of tasks depends on whether they are facilitated by either
      wakefulness or vigor.

PMID- 12502161
TI  - Fixation disparity: binocular vergence accuracy for a visual display at different
      positions relative to the eyes.
AB  - Some observers do not fixate accurately at the point of regard: Their vergence
      angle (between the visual axes of the two eyes) may correspond to points slightly
      nearer or farther away. This vergence error, or fixation disparity, was measured
      with nonius (vernier) lines at six positions of a visual display relative to the
      eyes. At viewing distances of 40, 60, and 100 cm, the display was located either
      at eye level or at a downward inclination of gaze direction of -25 degrees
      relative to horizontal. Viewing conditions resembled typical office work.
      Lowering the screen induced a near shift in mean vergence response of 0.6 min
      arc, irrespective of viewing distance; the closer the screen, the more distant
      was the vergence response relative to the target (by 2.5 min arc on average). The
      slope of this proximity-fixation-disparity curve is an individual parameter of
      the vergence system. Actual or potential applications of this research include
      recommendations for the comfortable viewing distance of visual displays.

PMID- 12502162
TI  - Visually induced motion sickness predicted by postural instability.
AB  - We investigated whether postural instability can predict motion sickness and
      studied relations among instability, motion sickness, and vection. Nine men and 4
      women (mean age = 19.85 years) were exposed, while standing, to an optical
      simulation of body sway. Head motion was recorded using a magnetic tracking
      system. Postural instabilities were observed prior to the onset of motion
      sickness. Vection was reported by most participants, including all who became
      ill. A discriminant analysis revealed that parameters of postural motion
      accurately predicted motion sickness. The results confirm that postural
      instability precedes motion sickness and suggest that measures of postural motion
      may serve as reliable predictors of motion sickness. Potential applications of
      this research include the development of on-line diagnostic tools that will allow
      for the prevention of motion sickness in operational and training settings.

PMID- 12502163
TI  - Risk attitude reversals in drivers' route choice when range of travel time
      information is provided.
AB  - Automobile drivers were recently found to be risk averse when choosing among
      routes that had an average travel time shorter than the certain travel time of a
      route considered as a reference. Conversely, drivers were found to be risk
      seeking when choosing among routes that had an average travel time longer than
      the certain travel time of the reference route. In a driving simulation study in
      which the reference route had a range of travel times, this pattern was
      replicated when thereference range was smaller than the ranges of the available
      routes. However, the pattern was reversed when the reference range was larger
      than the ranges of the available routes. We recently proposed a simple heuristic
      model that fit the relatively complex data quite well. Actual or potential
      applications of this research include the design of variable message signs and of
      route choice support systems.

PMID- 12502164
TI  - Headway feedback improves intervehicular distance: a field study.
AB  - The effectiveness of a headway measuring and recording device was evaluated in
      terms of its ability to increase drivers' car-following distance. Forty-three
      drivers first drove for approximately 3 weeks without headway feedback and then
      for approximately 3 more weeks with immediate time headway (THW) feedback.
      Whenever the THW decreased to 1.2 s or less a red warning light came on, and
      whenever the THW decreased further to 0.8 s or less a buzzer was also sounded.
      The results showed that prior to receiving THW information,drivers drove at
      shorter headways than after they received that information. The effect of the
      feedback was to reduce the time spent in short headways (< or = 0.8 s) by
      approximately 25% (from 20% to 15% of the time) and to increase the time spent in
      safer longer headways (>1.2 s) by approximately 20% (from 57% to 65% of the
      time). The effect was similar for younger and older drivers, for male and female
      drivers, for urban and highway speeds, and for daytime and nighttime driving. An
      immediate application of these findings is to install headway feedback displays
      to drivers so that they may maintain safer headway distances than they do
      currently.

PMID- 12502165
TI  - Age and visual impairment decrease driving performance as measured on a closed
      road circuit.
AB  - In this study the effects of visual impairment and age on driving were
      investigated and related to visual function. Participants were 139 licensed
      drivers (young, middle-aged, and older participants with normal vision, and older
      participants with ocular disease). Driving performance was assessed during the
      daytime on a closed-road driving circuit. Visual performance was assessed using a
      vision testing battery. Age and visual impairment had a significant detrimental
      effect on recognition tasks (detection and recognition of signs and hazards),
      time to complete driving tasks (overall course time, reversing, and maneuvering),
      maneuvering ability, divided attention, and an overall driving performance index.
      All vision measures were significantly affected by group membership. A
      combination of motion sensitivity, useful field of view (UFOV), Pelli-Robson
      letter contrast sensitivity, and dynamic acuity could predict 50% of the variance
      in overall driving scores. These results indicate that older drivers with either
      normal vision or visual impairment had poorer driving performance compared with
      younger or middle-aged drivers with normal vision. The inclusion of tests such as
      motion sensitivity and the UFOV significantly improve the predictive power of
      vision tests for driving performance. Although such measures may not be practical
      for widespread screening, their application in selected cases should be
      considered.

PMID- 12502166
TI  - Using animation to help students learn computer algorithms.
AB  - This paper compares the effects of graphical study aids and animation on the
      problem-solving performance of students learning computer algorithms. Prior
      research has found inconsistent effects of animation on learning, and we believe
      this is partly attributable to animations not being designed to convey key
      information to learners. We performed an instructional analysis of the to-be
      learned algorithms and designed the teaching materials based on that analysis.
      Participants studied stronger or weaker text-based information about the
      algorithm, and then some participants additionally studied still frames or an
      animation. Across 2 studies, learners who studied materials based on the
      instructional analysis tended to outperform other participants on both near and
      far transfer tasks. Animation also aided performance, particularly for
      participants who initially read the weaker text. These results suggest that
      animation might be added to curricula as a way of improving learning without
      needing revisions of existing texts and materials. Actual or potential
      applications of this research include the development of animations for learning
      complex systems as well as guidelines for determining when animations can aid
      learning.

PMID- 12502167
TI  - Gender differences in the experience of intimate partner violence among active
      duty U.S. Army soldiers.
AB  - The relationship of intimate partner violence to psychological distress and the
      mediating or moderating effects of social support were examined among 99 married
      active duty Army women and 477 married active duty Army men. Although
      approximately 40% of both the men and the women had experienced physical partner
      violence in the past year, in neither group was physical violence correlated with
      psychological distress when controlling for other variables. Among women,
      psychological abuse inflicted by a partner was significantly associated with
      greater psychological distress. Among men, poor marital adjustment was associated
      with greater psychological distress. An unexpected significant interaction effect
      was found among women indicating that those who were violent toward their
      partners under conditions of high peer support experienced greater psychological
      distress.

PMID- 12502168
TI  - Nontraumatic exercise-related deaths in the U.S. military, 1996-1999.
AB  - We identified 215 exercise-related deaths in U.S. military personnel on active
      duty during 1996-1999. The most complete case information was for active duty
      Army personnel during 1998-1999, providing an exercise-related death rate of 4.3
      per 100,000 person-years (41/963,000) and accounting for 6% of Army deaths (14
      during physical fitness testing). The cause of death was confirmed by autopsy or
      clinical data for 85% of the cases. Arteriosclerotic coronary artery disease was
      the predominant cause of death for those 30 to 58 years of age. For age 17 to 34
      years, 50% of deaths were attributable to preexisting heart disease (16% from
      coronary anomalies), 20% attributable to nontraumatic drowning, and 12%
      attributable to exertional heat illness, also a potential contributory factor in
      cardiac deaths. Most exercise-related deaths were related to running (60%),
      sports (14%), and swimming (13%). Improvements in health promotion, medical
      management, and stricter exclusion from inappropriate exercise (especially
      fitness test runs) could reduce these deaths.

PMID- 12502169
TI  - Injury occurrence and risk factors in construction engineers and combat artillery
      soldiers.
AB  - OBJECTIVES: This 1-year prospective study compared 125 construction engineers and
      188 combat artillery soldiers to determine whether there were differences in
      injury occurrences/ types because of their diverse occupational tasks and
      training requirements. Also, intrinsic factors were studied to establish any
      associations with a soldier's risk for injury. METHODS: Prestudy height, weight,
      and body mass index and fitness (3.2-km run, sit-ups, push-ups) data were
      collected prior to the injury medical records review. Approximately 30% of each
      battalion was studied. RESULTS: For engineers and artillery, 86.0% and 66.0%
      incurred at least one injury, respectively. Of total soldiers, 64.0% of engineers
      and 56.4% of artillerymen had injuries associated with limited duty profiles.
      Total injuries resulted in 743 days of limited duty time (5.9 days per soldier)
      in engineers and 1,078 days (5.7 days per soldier) in artillery. Odds ratios (OR)
      and 95% confidence intervals (CI) were also calculated. The odds of traumatic
      fractures were (OR = 6.5, 95% CI = 1.8-23.7) 6 times higher in engineers than
      artillery, but strains/sprains and abrasions/lacerations were (OR = 2.3, 95% CI =
      1.5-3.7; OR = 2.5, 95% CI = 1.2-5.0) two times higher in artillery than
      engineers. The number of limited duty days associated with knee injuries was
      significantly higher in engineers than artillery (p < 0.0001), and number of days
      for low back injuries was significantly higher in the artillerymen (p < 0.0001).
      Greater body mass was a risk factor for lower back pain and the body mass index
      was > or = 25 for strains/sprains in both units. CONCLUSIONS: Significant
      differences in injuries were reported between the two units. It is plausible that
      the differences were related to the diverse training exposures of the units.
      However, it is beyond the scope of this study to make conclusions about the
      causes of the injury differences. The data also indicate that body mass and body
      mass index were identified as modifiable injury risk factors for both units,
      which suggests that these injuries are preventable.

PMID- 12502170
TI  - The treatment of infected tibial nonunion with aggressive debridement and
      internal bone transport.
AB  - Tibial nonunions are a challenging situation for both healing and reconstruction
      when infection is added. In this retrospective study, we discuss the cases in
      which we had managed to obtain union by aggressive debridement, circular external
      fixature, and internal bone transport. Fourteen cases had been treated between
      January 1995 and December 2000 in the Orthopedics and Traumatology Department of
      the Gulhane Military Medical Academy. The mean follow-up period was 33.2 (12-60
      months) months. The mean length of defects was 4.4 (2.5-8 cm) cm. These defects
      were repaired by corticotomy and by internal bone transport only. Pseudoarthrosis
      and union of corticotomy sites occurred in a mean period of 6.8 (4.5-15) months.
      In two of our patients, reinfection occurred, and hyperbaric oxygen therapy was
      applied to them. We concluded that in tibial infected nonunions, satisfactory
      union and control of infection are possible by radical debridement, stable
      fixation by circular external fixature, osteotomy and callus distraction,
      antibiotic therapy, and hyperbaric oxygen therapy whenever needed.

PMID- 12502171
TI  - Occupational psychiatry services in a military setting.
AB  - Occupational psychiatry services have become increasingly important since the
      passage of the Americans with Disabilities Act and the recent growth of workers'
      compensation mental health claims. Delivery of such services within the military
      is complicated by interagency financial relationships, recent implementation of a
      comprehensive managed care program, and military regulations governing medical
      services. In this article, we describe the provision of occupational psychiatry
      services in a large military medical system and present the results of a
      feasibility study of establishing a regular clinic to improve them. The results
      of the study highlighted the importance of having occupational psychiatry
      services available within the medical center, although it did not establish the
      necessity of a specific clinic to provide these services. Case material is
      presented that illustrates our approach and the range of services encompassed.

PMID- 12502172
TI  - Life-threatening polyneuropathy heralding renal cell carcinoma.
AB  - OBJECTIVE: To report the occurrence of life-threatening polyneuropathy in
      association with renal cell carcinoma. METHODS: Case report and review of the
      medical literature. RESULTS: A 65-year-old man developed a fulminant, life
      threatening sensory motor polyneuropathy several months before renal cell
      carcinoma was identified. Dramatic symptomatic improvement ensued after treatment
      with intravenous immunoglobulin, although the patient succumbed to complications
      of the tumor years later. CONCLUSIONS: Chronic sensory motor polyneuropathy is a
      known paraneoplastic syndrome associated with renal cell carcinoma. This report
      emphasizes that in rare conditions, the polyneuropathy could take an acute
      demyelinating form, which is important for clinicians to recognize.

PMID- 12502173
TI  - Imported furuncular myiasis in Germany.
AB  - Furuncular myiasis is a parasitic infestation of human and other vertebrate
      tissues by fly larvae of primarily two species: Dermatobia hominis (human botfly,
      t6rsalo, or berne) in Mexico and South and Central America and Cordylobia
      anthropophaga (tumbu fly or mango fly) in Africa. Cuterebra species (rabbit and
      rodent botflies) are also rarely reported to cause furuncular myiasis only within
      the United States. Although these species inhabit different geographic regions
      and have different life cycles, their clinical presentations can be similar. We
      describe a case of "imported" human botfly (D. hominis) furuncular myiasis in a
      U.S. Army soldier stationed in Germany. We review the life cycles of human
      botflies and key aspects of their clinical presentation, differential diagnosis,
      and various therapeutic modalities. Most physicians may never encounter myiasis
      and attribute a patient's complaints to an insect bite or skin infection that
      will heal without treatment. However, the diagnosis of furuncular myiasis should
      be considered by remembering the basic elements of this condition: recent travel
      history to the tropics and a sterile, persistent furuncle with sensations of
      movement and pain.

PMID- 12502174
TI  - Body fat standards and individual physical readiness in a randomized Army sample:
      screening weights, methods of fat assessment, and linkage to physical fitness.
AB  - Body fat standards have been used by the military services since the early 1980s
      to prevent obesity and motivate good fitness habits. The Army Weight Control
      Program has continued to undergo evaluation and incorporate improvements based on
      emerging scientific findings. Recently drafted revisions of Department of Defense
      wide procedures address issues of consistency and validity raised by external
      oversight groups. This study evaluated the impact of three proposed refinements
      of the Army Weight Control Program. Anthropometric measurements and fitness test
      performance were obtained in a randomized sample of 1,038 male and 347
      nonpregnant female soldiers at three Army posts. Of this sample, 11% of men and
      17% of women were overweight and overfat; 6.3 and 9.8%, respectively, were
      currently on the Army Weight Control Program. Screening weight tables that ensure
      women are not inappropriately striving to meet weights more stringent than
      "healthy" weight (i.e., body mass index < 25 kg/m2) still correctly identified
      all women for evaluation for the age-specific body fat standards. Body fat
      estimation using more valid DoD body fat equations that include an abdominal
      circumference for women reduced the number of female soldiers currently
      classified as exceeding fat standards, coincidentally resulting in a comparable
      prevalence of male and female soldiers over the fat standards (12%). A body fat
      allowance for young soldiers who scored very well on the physical fitness test
      could have benefited one-fourth of the soldiers exceeding fat standards and
      acknowledges biological variability in body fat thresholds. Whereas this linkage
      may motivate fitness habits, it complicates enforcement of reasonably achievable
      body fat standards. The proposed changes in fat screening and measurement methods
      are appropriate, but the impact to health and physical readiness of the Force
      cannot be accurately predicted or measured because of the absence of
      comprehensive baseline data and tracking mechanisms.

PMID- 12502175
TI  - SMOKED: a pharmacist-monitored tobacco cessation program.
AB  - Tobacco users use an array of pharmaceutical aids in their quest to become
      tobacco free. Tobacco cessation aids are indicated to assist individuals to
      become tobacco free when used in conjunction with a behavior modification
      program. For many persons, attending traditional group behavioral modification
      classes of 1- to 2-hour weekly meetings for 4 to 6 weeks is either undesirable or
      impractical. This article describes a nontraditional tobacco cessation program
      offered by a pharmacist at a Coast Guard military treatment facility. The program
      required persons desiring tobacco cessation aids to see a medical provider who
      then referred the individual to the pharmacy officer for counseling. Of the 20
      persons completing all designated counseling sessions with the pharmacy officer,
      4 were tobacco free after 1 year.

PMID- 12502176
TI  - Food for thought: the use of hazard and critical control point analysis to assess
      vulnerability of food to terrorist attack in deployment locations.
AB  - As part of a screening study, a literature review, personal interviews, and field
      work at several deployment locations, we examined the historical use of
      biological warfare agents and the vulnerability of food at military deployment
      locations to bioterrorist attack. The results of our experience suggest the
      following: historically, food has occasionally been used as a weapon by
      individuals; a benchmark procedure already exists to evaluate and ensure the
      safety of foods procured and used by the U.S. federal government; and food
      sources at the deployment locations examined are vulnerable to terrorist attack
      as determined by a critical control point analysis. Recommendations to
      potentially decrease the vulnerability of the U.S. military food supply to
      intentional contamination are also provided.

PMID- 12502177
TI  - Influence of oral health on combat readiness in the Croatian army.
AB  - The impact of the acute stomatological conditions on the reducing of the combat
      readiness is an important responsibility for the military planners.
      Classification of dental health is the primary condition for research and
      assessment of the army dental readiness for combat. Clinical examination of teeth
      and mouth included 912 soldiers, 650 of whom were recruits and 262 active duty
      military personnel. According to their oral status, the examinees were divided
      into three classes. Class 1 included all those examinees that did not require any
      dental treatment or reevaluation within 12 months. Class 2 included all of the
      examinees whose oral health was such that if regularly controlled or followed up,
      they were not expected to have a dental emergency within 12 months. Class 3
      included all of the examinees that required dental treatment to correct both
      their dental and oral health because the present condition was likely to cause
      acute stomatological conditions during the 12-month period. This survey
      designated 130 (14.3%) of the examinees to class 1,178 (19.5%) to class 2, and
      604 (66.2%) to class 3. The combat readiness of the 604 (66.2%) examinees in the
      third class was reduced because a dental emergency can cause the need for dental
      treatment. The recruits do not have satisfactory dental status even at the
      beginning of their army service. Unfortunately, active duty military personnel do
      not have satisfactory dental status either, although they have access to cost
      free dental care (prosthetics and orthodontics are not included). This increases
      the possibility for development of dental emergencies that would have a negative
      impact on combat readiness.

PMID- 12502178
TI  - Choline ingestion does not modify physical or cognitive performance.
AB  - OBJECTIVES: This study was undertaken to determine whether choline ingestion
      improves physical and cognitive performance following exhaustive load carriage
      exercise. METHODS: In a double-blind crossover study, 13 men (28 +/- 2 years)
      underwent four test sessions: load carriage treadmill and no-load carriage test
      sessions after taking choline or placebo. Physical and cognitive performance
      batteries were administered at the end of the test sessions. RESULTS: Choline
      ingestion (50 mg/kg body weight) significantly (p < 0.05) increased plasma
      choline concentrations during the load and no-load carriage test sessions.
      However, plasma choline did not decrease during the placebo load carriage test
      session, an indication that load carriage does not deplete circulating choline.
      There were no differences in performance on physical tasks, and choline ingestion
      had no effect on reaction time, logical reasoning, vigilance, spatial memory, or
      working memory. CONCLUSION: In healthy men, supplemental choline did not affect
      physical or cognitive performance after exhaustive physical activity.

PMID- 12502179
TI  - The Armstrong Laboratory Aviation Personality Survey: development, norming, and
      validation.
AB  - This work describes the development of a new psychological test for aviators. The
      Armstrong Laboratory Aviation Personality Survey was developed through the
      integration of clinical theory, psychometric methods, and empirical testing. It
      is currently given to all incoming U.S. Air Force pilot candidates. Using a
      sample of 6,047 student pilots, a thorough test development plan was
      accomplished. The 15 final test scales assess personality, psychopathology, and
      crew interaction styles. The scales have normative data and are demonstrated to
      be reliable and valid. The Armstrong Laboratory Aviation Personality Survey is
      recommended for use in the aviation community for both clinical and research
      purposes. Future research is recommended and needed in the areas of training,
      airframe, and special duty selection. Additional clinical work is indicated in
      the areas of psychiatric, psychological, and aeromedical evaluations.

PMID- 12502180
TI  - Musculoskeletal injuries in an Army airborne population.
AB  - To maintain operational readiness, military personnel engage in vigorous physical
      and training activities that carry risk for injury. A 1-year prospective cohort
      study, starting April 1996, was conducted at Fort Bragg, North Carolina among
      1,965 members of the 82nd Airborne Division to quantify musculoskeletal injuries.
      Information collected included type of injury, site, circumstances, and resultant
      limited duty days. These soldiers suffered 508 overuse injuries (including 38
      stress fractures), 1,415 traumatic injuries (including 100 fractures), and 101
      unclassified injuries. Injury rates were 6.8% per soldier per month for traumatic
      injury and 2.4% for overuse injury (totaling 1.2 injuries per soldier per year).
      Injuries resulted in 22,041 limited duty days, averaging 11 days per injury and
      13 days per soldier (4.5% of total workdays). Fractures and stress
      fractures/reactions produced the most days lost per case. Most of these injuries
      resulted from military-specific activities.

PMID- 12502181
TI  - Diagnosis of Plasmodium vivax malaria complicated by abnormal neurological
      imaging.
AB  - The number of patients presenting with malaria in the United States has
      increased. This is attributable to the growing ease and popularity of overseas
      travel. We present a 41-year-old man diagnosed with Plasmodium vivax malaria
      after a 9-month symptom-free interval following return from an endemic area. The
      clinical picture was complicated by the results of neurological imaging that
      proved to be incidental and unrelated findings. Unfortunately, there are no
      pathognomonic signs or symptoms of malaria. The presenting complaints are often
      nonspecific and may be associated with a broad differential diagnosis. Thus,
      physicians must have a high index of suspicion and elicit a complete travel
      history to arrive at the correct diagnosis.

PMID- 12502182
TI  - Explosive ordinance disposal team equipment and its use in diagnosing extremity
      trauma.
AB  - A 31-year-old man presented to the Rakkasan battalion aid station, located at the
      Qandahar Airport, Afghanistan, with complaints and physical findings consistent
      with those that would either support a grade III ankle sprain or fracture. The
      battalion aid station is an echelon I level of care. This facility does not have
      radiographic capabilities. With the closest radiology facility located in Seeb,
      Oman the 710th Explosive Ordinance Disposal team, which was operating in the
      area, was contacted. This unit was able to perform radiographs in a timely manner
      to help aid in correctly diagnosing the injury.

PMID- 12502183
TI  - Histone mRNA in situ hybridization in assessing proliferative activity of normal
      and malignant cells.
AB  - Proliferative capacity is an important determinant of tumour biological
      behaviour. For research and diagnostic purposes, immunohistochemical techniques
      are usually applied in the assessment of tissue proliferative status. An
      interesting alternative for these studies is a detection of histone mRNA. As the
      synthesis of histones is tightly coupled with DNA replication during S-phase of
      the cell cycle, histone mRNA level is a specific marker of S-phase cells.
      Furthermore, a short-lived transcript guarantees accurate estimation of S-phase
      cell pool at the moment of tissue fixation. The progress in molecular biology
      techniques during the last decade made possible the use of in situ hybridization,
      especially its non-radioactive version, in routine laboratory services. This
      technique can be successfully applied to detection of histone mRNA in routinely
      processed tissues. Advantages and limitations of such approach in tumour
      proliferation studies are discussed.

PMID- 12502184
TI  - IL-1-mediated inhibition of IL-6-induced STAT3 activation is modulated by IL-4,
      MAP kinase inhibitors and redox state of HepG2 cells.
AB  - It is known that during acute phase reaction IL-6 activates STAT3 in hepatoma
      cells and IL-1 downregulates this response. We found that the inhibitory
      properties of IL-1 on STAT signalling cascade in human hepatoma HepG2 cells are
      considerably decreased not only in the presence of MAP kinase inhibitors SB203580
      and PD98059 but also by some antioxidants (N-acetyl cysteine and pyrrolidine
      dithiocarbamate) and by anti-inflammatory cytokine IL-4. It appears that cytokine
      crosstalk between IL-6 and IL-1 includes a direct pathway sensitive to
      antioxidants and MAP kinase inhibitors, whereas the indirect prolonged response
      depends probably on synthesis of suppressors of cytokine signalling (SOCS).

PMID- 12502185
TI  - Expression of TCR-zeta chain and apoptosis in subpopulations of tumor-associated
      lymphocytes (TALs) from malignant pleural effusions.
AB  - Malignant effusions in serous cavities represent suspension of tumors and
      inflammatory cells and therefore present an attractive model for studying tumor
      host interactions. T cell functional ability is linked to proper signal
      transduction via T cell receptor (TCR-CD3 complex), especially its zeta chain.
      The latter has been found to be often depressed in malignancy. Aim of this study
      was to assess alterations of zeta chain expression and its relation to apoptosis
      of T lymphocytes. T lymphocytes obtained from pleural effusions of 20 cancer
      patients and 9 patients with nonmalignant effusions serving as a control were
      studied. The analysis was performed using flow cytometry combining CD3, CD 4,
      CD8, CD 16/56, TCR-zeta and TUNEL reaction. In the control group, T lymphocytes
      obtained from pure lymphocyte effusions had constantly high level of zeta chain
      while those from malignant pleural effusions had a decreased zeta chain
      expression. Lymphocytes with low zeta chain expression were the main
      subpopulation of T cells undergoing apoptosis.

PMID- 12502186
TI  - The compounds from the hollyhock extract (Althaea rosea Cav. var. nigra) affect
      the aromatization in rat testicular cells in vivo and in vitro.
AB  - Among medicinal plants, extract from the hollyhock flowers is a source of
      antocyanides and flavonoids. The latter compounds belong, among others, to
      phytoestrogens (plant-derived dietary estrogens). The important role of estrogens
      in the testis is now well documented, and phytoestrogens, which may act as
      estrogen agonists or estrogen antagonists can also alter the reproductive
      function of the male. The aim of this study was to show whether the exposure of
      male rats to the aqueous hollyhock extract could affect the process of
      aromatization in their testes and in cultured Leydig cells. This was investigated
      by immunocytochemistry and radioimmunological assays. Immunoreactivities for
      aromatase and estrogen receptor beta were weaker both in testicular sections and
      cultured Leydig cells after hollyhock extract administration when compared to the
      controls, while the intensity of immunoreaction for estrogen receptor alpha
      remained unchanged. A lower level of estradiol secreted by cultured Leydig cells
      from the experimental group positively correlated with a direct inhibition of
      aromatase activity. Additionally, a quantitative analysis of flavonoid fraction
      from the hollyhock extract revealed the presence of quercetin and kaempferol. It
      seems that a weak antiestrogenic activity of flavonoid compounds present in the
      hollyhock extract is mediated through aromatase and estrogen receptor beta rather
      than by estrogen receptor alpha.

PMID- 12502187
TI  - Distribution of spinal sensory neurons supplying the adrenal gland in the pig.
AB  - The present study was aimed at disclosing which spinal ganglia contribute to the
      innervation of the adrenal gland in the pig with special regard to the morphology
      and intraganglionic distribution of the primary sensory neurons within these
      ganglia. To this end, the animals were injected with a retrograde fluorescent
      neuronal tracer Fast Blue into the left adrenal gland during laparotomy. After a
      survival period of three weeks, labelled spinal sensory neurons were found in the
      ipsilateral dorsal root ganglia (approximately 99% of all retrogradely marked
      neurons). However, single adrenal gland-projecting perikarya were observed also
      in the contralateral dorsal root ganglia from Th3 to L3. The majority of the
      retrogradely labelled afferent neurons (above 65% of all Fast Blue-positive (FB+)
      perikarya) were located in two groups of spinal ganglia (at neuromeres Th6-7 and
      Th12-14, approximately 18% and 47% of neurons, respectively), forming two
      distinct multiganglionic centres of origin for this neural pathway. The
      morphometric evaluation of FB+ neurons revealed that the vast majority of them
      (approximately 81%) belonged to the class of small-sized perikarya (10-30 microm
      in diameter), while the medium-sized (diameter 30-80 microm) and large neurons
      comprised only up to 13% and 6.5% of adrenal gland-projecting neurons,
      respectively. Furthermore, the analysis of the intraganglionic distribution
      pattern of the retrogradely labelled cells revealed that the highest number of
      them was located in the medio-caudal domain of the dorsal root ganglia,
      irrespective of the neuromere studied. Thus, the present study has revealed
      sources and morphological characteristic of spinal afferent neurons supplying the
      porcine adrenal gland, simultaneously pointing out to the characteristic features
      of their inter- and intraganglionic distribution pattern.

PMID- 12502188
TI  - Distribution of primary afferent neurons associated with the porcine inferior
      mesenteric ganglion (IMG).
AB  - The existence of afferent neurons supplying IMG nerve cells by their collaterals
      has previously been demonstrated in laboratory animals, where these fibers
      constitute an important part of intraganglionic nerve input involved in the
      regulation of autonomic neurons activity. The domestic pig is thought to be a
      reliable animal model for medical and biomedical studies, especially those
      dealing with the organization of nerve pathways contributing to the neural
      control of the bowel and lower urinary tract functions. However, there is no data
      dealing with the existence and distribution of spinal afferent neurons that may
      be involved in the integration of various stimuli at the level of IMG, one of the
      most important nerve centers controlling these organs. Therefore, the present
      study was aimed at disclosing the distribution and morphological features of
      sensory neurons associated with the porcine IMG by means of retrograde tract
      tracing technique. To this purpose, the right IMG was injected with the
      retrograde neuronal tracer Fast Blue (FB) in five immature female piglets of
      Large Polish White race and the distribution of FB-positive neurons in dorsal
      root ganglia (DRG) of interest was studied three weeks later. Retrogradely
      labelled perikarya were found in both left and right DRG Th15-L5, however, with a
      clear lateralization in the bilateral projections pattern. The number of
      contralaterally located IMG-projecting perikarya distinctly decreased towards the
      caudal direction, constituting approximately 23%, 20%, 16%, 6.5%, 4% and 0% of
      all FB-positive neurons found in both left and right DRG at neuromeres Th15-L5,
      respectively. The majority of FB-positive neurons (approximately 90% of all
      traced cells) were found in bilateral L2 and L3 DRG. The largest part of IMG
      projecting sensory neurons (68.9 +/- 5.0%), irrespective of their location,
      belonged to the class of medium-sized perikarya (diameter from 30 to 80 microm).
      The present study provides a detailed description of distribution and
      morphological characteristics of spinal afferent neurons projecting to the
      porcine IMG, simultaneously demonstrating typical features of their inter- and
      intraganglionic distribution pattern. Furthermore, the present results strongly
      suggest that spinal afferents contribute to the co-ordination and integration of
      peripheral reflexes involving sympathetic IMG neurons.

PMID- 12502189
TI  - Immunolocalization of PTHrP in prepubertal and pubertal testis of European bison.
AB  - The present study deals with immunohistochemical localization of PTHrP in
      prepubertal and pubertal testis of European bison. PTHrP immunoreactivity was
      observed in germinal cells in the testis of both prepubertal and pubertal
      animals. In calves, PTHrP was found in germinal cells, in seminiferous tubules
      lacking the lumen. The reaction was strong and regularly distributed within the
      cytoplasm. In adult animals, the reaction showed differentiation in spermatogenic
      cells. Some cells were strongly and diffusely stained, others exhibited weaker
      reaction of granular pattern. Sertoli cells and Leydig cells were PTHrP-negative
      in calves and adult animals.

PMID- 12502190
TI  - Immunoexpression of nm23 in advanced esophageal squamous cell carcinoma.
AB  - The study was undertaken to determine the immunoexpression of protein products of
      nm23 genes which are thought to be potential metastasis suppressor genes, in
      esophageal squamous cell carcinoma, and to analyze their relationship to selected
      clinicopathological features (age, sex, tumour size, depth of invasion, presence
      of lymph nodes and distant metastasis, pathologic tumor stage, degree of cancer
      differentiation and vascular/lymphatic invasion), as well as to the overall
      survival. Immunohistochemical staining with monoclonal antibody against nm23
      using LSAB2/HRP method on formalin-fixed, paraffin-embedded sections obtained
      from 32 tumors was performed. Eight tumors (25%) showed positive nm23
      immunoexpression. There were no statistically significant differences between
      nm23-positive and nm23-negative groups with respect to all clinicopathological
      features studied. The positive nm23 status was related to a worse prognosis but
      this was not significant. The results may suggest that nm23-status is not
      associated with metastatic ability and prognosis in esophageal squamous cell
      carcinoma, but such thesis requires further study on a larger population.

PMID- 12502191
TI  - The effect of pre-eclamptic umbilical cord serum on fibroblast division in
      culture.
AB  - Edema, proteinuria, hypertension (EPH-gestosis), most commonly termed as pre
      eclampsia, is the most common pregnancy-associated pathological syndrome. It is
      accompanied by a thorough remodelling of extracellular matrix in the umbilical
      cord tissues. It is commonly known that the presence of serum in culture medium
      strongly stimulates many functions of cells cultured in vitro. It was decided to
      check how the pre-eclamptic serum affects the fibroblast division in culture. Ki
      67 is a protein present in proliferating cells and can be detected during all
      phases of the cell cycle (G1, S, G2/M) but not in resting (G0) cells. PCNA
      (proliferating cell nuclear antigen) is an intranuclear polypeptide whose
      synthesis rate is at its maximum during the S-phase of the cell cycle. The
      expression of Ki-67 and PCNA was measured by immunocytochemical methods and
      biosynthesis of DNA was evaluated by [14C]-thymidine incorporation. The activity
      of pre-eclamptic umbilical cord serum (UC-serum) was found to be distinctly lower
      in comparison to control one. The expression of Ki and PCNA in fibroblast
      cultures treated with pre-eclamptic serum was also distinctly lower. Also the
      incorporation of [14C]-thymidine to DNA was lower than in the cultures treated
      with control UC-serum. It may by concluded that pre-eclampsia reduces the
      mitogenic activity of the umbilical cord serum.

PMID- 12502192
TI  - Iatrogenic Chlamydia infection-associated damage in the basilar arterial wall of
      the rat.
AB  - A random finding of intracranial vascular Chlamydia sp. infection in Wistar rats
      and its associated damage of the component tissues of the basilar arterial wall
      are described as seen with transmission electron microscopy. The pathological
      changes observed showed no apparent specificity except for "striding" of the
      endothelial cells on the elastic lamina, the phenomenon observed in all five rats
      with basilar arterial Chlamydia infection, and in only two out of 13 rats with no
      proof of the infection. No atherosclerotic changes were found in the infected
      artery in rats sacrificed 8 or 26 weeks after the presumed infection.

PMID- 12502193
TI  - Tiered medical care: will the patient pay for it?

PMID- 12502194
TI  - Update on cartilage repair.

PMID- 12502195
TI  - Radiologic case study. Benign intraosseous lipoma.
AB  - Intraosseous lipomas are uncommon lesions of bone most often diagnosed
      incidentally. They typically manifest a classic radiographic appearance, but CT
      or MRI may be useful in diagnosing lesions that are atypical or incompletely
      defined radiographically and avoid an unnecessary biopsy.

PMID- 12502196
TI  - Minimal incision acromioplasty.

PMID- 12502197
TI  - The effect of implant constraint on results of conversion of unicompartmental
      knee arthroplasty to total knee arthroplasty.
AB  - A series of unicompartmental knee arthroplasty (UKA) revision to total knee
      arthroplasty (TKA) was compared to a group of primary TKAs performed at the same
      institution. The UKA revision group had a higher incidence of local wound
      complications and inferior clinical results as measured by Knee Society scores.
      When the revisions were stratified by the degree of interface constraint, knees
      revised with posterior cruciate ligament (PCL) substituting designs had superior
      knee scores that were comparable to the primary group. The use of a PCL
      substituting knee design is recommended when converting a UKA to TKA.

PMID- 12502198
TI  - Correlation of the change in the International Normalized Ratio and decreasing
      the Coumadin dosage following total joint arthroplasty.
AB  - This retrospective pilot study determined whether a change in the daily
      International Normalized Ratio (INR) correlates with a decrease in Coumadin
      (DuPont Pharma, Wilmington, Del) dosage. Four hundred seventeen patients yielded
      1167 pairs of INR values and Coumadin doses. An increase in INR > 0.4 units
      correlated 81% with a decrease in the Coumadin dose (P < .05). In patients aged >
      or = 70 years, the correlation fell to 70% compared to an 89% correlation in
      patients aged < 70 years (P < .05). The correlation fell to 78% in women, while
      men exhibited an increase to 87% (P < .05). Although this is a pilot study, when
      managing postoperative Coumadin anticoagulation for orthopedic patients, an
      increase in INR > 0.4 units correlates highly with the need to decrease the
      Coumadin dose. A prospective study is needed to test the usefulness of this
      parameter.

PMID- 12502199
TI  - Femoral neck and intertrochanteric fractures: radiographic indicators of fracture
      healing.
AB  - Serial hip radiographs from 280 patients with proximal femoral fractures were
      analyzed retrospectively by 3 radiologists to evaluate conventional radiographic
      healing patterns. Patients with hemiarthroplasty or insufficient follow-up were
      excluded. In the remaining 41 patients, the fracture line and callus was
      assessed. Intertrochanteric fractures demonstrated increasing callus and
      sclerosis at the fracture site. No such association was seen in femoral neck
      fractures. Traditional indicators of fracture healing cannot be readily applied
      at the hip. Radiographic features relate more to fracture type and fixation
      method.

PMID- 12502200
TI  - Analysis of retrieved uncemented porous-coated acetabular components in patients
      with and without pelvic osteolysis.
AB  - Retrieved polyethylene liners and femoral heads from a consecutive series of
      revision components of one design were examined. All patients had Long-Term
      Stable Fixation (OsteoTechnology International, Timonium, Md) total hip
      arthroplasties (THAs) implanted between 1987 and 1992. The retrieved femoral
      heads and liners from patients with osteolysis were compared to those without
      osteolysis. Patients with osteolysis had significantly thinner polyethylene (5.1
      mm versus 7.4 mm, P<.01 ) and a higher linear wear rate (0.5 mm/y versus 0.3
      mm/y, P=.05). The average femoral head surface roughness also was significantly
      greater in patients with osteolysis (67 nm versus 35 nm, P<.05). Patients with
      osteolysis had more total volumetric wear, total linear wear, and volumetric wear
      rate compared to patients without osteolysis. Age, obesity index, time in situ,
      and cup inclination were not different between the two groups. Excessive
      polyethylene wear, probably accelerated by surface roughness of the femoral
      heads, was associated with pelvic osteolysis in these patients.

PMID- 12502201
TI  - The muscle bed--a crucial factor for fracture healing: a physiological concept.

PMID- 12502202
TI  - Stem modularity: rarely necessary in primary total hip arthroplasty.
AB  - A retrospective review of two consecutive series of cementless primary THA
      performed simultaneously from November 1987 to February 1994 within a single
      orthopedic practice by three surgeons was conducted. A series using non-modular
      Mallory-Head Porous (Biomet Inc, Warsaw, Ind) femoral components was compared to
      a series using modular Sivash Range of Motion (DePuy, Warsaw, Ind) femoral
      components to evaluate whether modularity of the femoral stem body is necessary
      in cementless primary THA. Clinically and radiographically, both components
      performed at comparable levels with equally satisfactory results. Both series
      demonstrated effective femoral fixation as evidenced by excellent Engh fixation
      scores. However, this study has shown the importance of circumferential proximal
      porous-coating to form an effective seal, preventing the propagation of
      particulate debris. Modular systems were associated with a higher degree of
      technical difficulty, operative time, and blood loss.

PMID- 12502203
TI  - Ilioinguinal neuralgia following anterior iliac crest bone harvesting.

PMID- 12502204
TI  - Fungal infection of a total knee prosthesis: successful treatment using
      articulating cement spacers and staged reimplantation.

PMID- 12502205
TI  - Upper extremity deep venous thrombosis following antegrade femoral nailing: case
      report and venographic study of operative positioning.

PMID- 12502206
TI  - The science of bone cement: a historical review.
AB  - The use of PMMA bone cement has been a key factor in the advent of joint
      replacement as a surgical option. Despite revolutionary changes in joint
      replacement technology for the treatment of hip and knee arthritis, the use of
      PMMA bone cement in its intraoperative application has not significantly changed
      since Harris' description of third generation cement technique. Future answers to
      questions regarding cemented implant longevity may lie in the further improvement
      of existing PMMA technology and standardization of the manufacturing of PMMA bone
      cement intraoperatively.

PMID- 12502207
TI  - Quo vadis capsule endoscopy?

PMID- 12502208
TI  - "The devil is in the details". Reflections on an "overview" of endoscopic
      treatment of post liver transplant bile duct strictures.

PMID- 12502209
TI  - Helicobacter pylori-induced duodenal ulcer frequently coincides with gastro
      oesophageal reflux disease.
AB  - BACKGROUND: The relationship between Helicobacter pylori infection and gastro
      oesophageal reflux disease is complicated. Evidence does not support a causal
      link. There have been reports, which have implicated successful eradication of
      Helicobacter pylori, in patients with a duodenal ulcer, with the subsequent
      development of gastro-oesophageal reflux disease. However, eradication of
      Helicobacter pylori in these patients with improvement in their condition and a
      return to normal lifestyle, weight gain and discontinuation of antacids may
      unmask pre-existing gastro-oesophageal reflux disease. AIMS: To determine the
      true prevalence of gastro-oesophageal reflux disease in patients with
      Helicobacter pylori-related duodenal ulceration. METHOD: Dyspeptic patients
      undergoing endoscopy were prospectively screened for the presence of a duodenal
      ulcer. Concomitant oesophagitis, when present, was recorded. All subjects with a
      Helicobacter pylori-related duodenal ulcer without endoscopic evidence of gastro
      oesophageal reflux disease were invited to undergo a 24-hr ambulatory oesophageal
      pH assessment prior to receiving treatment. RESULTS: A total of 97 patients with
      a duodenal ulcer were identified and 83.5% were Helicobacter pylori positive.
      Overall, 27.8% had associated endoscopic evidence of oesophagitis, 70% grade I-II
      and 30% grade III-IV. Of those without evidence of oesophagitis at endoscopy, 68%
      underwent a 24-hr pH assessment. An additional 17% were identified by this means
      as having gastro-oesophageal reflux disease. Overall, 44% of symptomatic subjects
      with Helicobacter pylori and a duodenal ulcer were found to have coexistent
      gastro-oesophageal reflux disease. CONCLUSION: Gastro-oesophageal reflux disease
      is frequently found to coexist with Helicobacter pylori-related duodenal ulcer.
      In addition, almost 20% of symptomatic patients without endoscopic evidence of
      oesophagitis will have an abnormal oesophageal pH exposure. It is plausible that
      the development of gastro-oesophageal reflux disease following successful
      eradication of Helicobacter pylori represents unmasking of existing disease
      rather than de novo development.

PMID- 12502210
TI  - Case control study on health-related quality of life in adult coeliac disease.
AB  - AIMS: To evaluate whether health-related quality of life in adult coeliac disease
      is related to: 1) adhesion to gluten-free diet; 2) manifestation of clinical
      features; and 3) associated diseases. PATIENTS AND METHODS: A total of 68 coeliac
      patients (54 female and 14 male) aged between 18 and 74 years, on gluten-free
      diet for at least two years were studied. The subjective health status was
      measured by means of the Short Form 36 Health Survey. A series of 136 subjects,
      matched according to sex, age and ethnic group, were evaluated as control group.
      RESULTS: Patients obtained worse scores with respect to healthy controls at all
      domains of Short Form 36 Health Survey (p<0.05); compliers showed better results
      than non-compliers. The lowest scores were obtained in patients with more than
      six symptoms, mostly in non-compliers, the highest in compliers with less than
      six symptoms. Patients with two or more associated diseases presented
      significantly worse scores than patients with only one associated disease.
      CONCLUSIONS: The importance of gluten-free diet in clinical management of coeliac
      disease is confirmed by results of the present study; moreover, the results seem
      to indicate that a complex interplay of factors should be taken into account in
      evaluating health-related quality of life in adult coeliac disease. Accordingly,
      our data show that health-related quality of life of coeliac patients is impaired
      not only by poor compliance but also by different negative factors such as
      severity of illness (in terms of number of symptoms) at diagnosis and
      comorbidity.

PMID- 12502211
TI  - Microsatellite instability in a population of sporadic colorectal cancers:
      correlation between genetic and pathological profiles.
AB  - BACKGROUND: Tumours with high-frequency microsatellite instability exhibit unique
      genotype and phenotype features, whereas the difference between low-frequency
      microsatellite instability and apparently stable tumours is far from being clear.
      AIMS: To identify distinctive genetic and pathological characteristics of low
      frequency microsatellite instability tumours. METHODS: Microsatellite instability
      status of 57 sporadic colorectal cancers and its correlation with genetic,
      pathological and clinical features was analysed. RESULTS: High frequency
      microsatellite instability and low-frequency microsatellite instability and
      apparently stable cancers were different in terms of tumour localisation
      (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's
      like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an
      adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability
      cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's
      like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite
      instability tumours were preferentially located in the right colon and exhibited
      a higher frequency of loss of heterozygosity at the FHIT locus compared with low
      frequency microsatellite instability and apparently stable cases (p=0.0243).
      Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer
      growth (p=0.0374), were the only factors affecting patient survival. However, a
      borderline improvement was noted in overall survival in high-frequency
      microsatellite instability and low-frequency microsatellite instability cancer
      patients (p=0.062). CONCLUSIONS: These results indicate that low-frequency
      microsatellite instability tumours have different genetics and histological
      features and suggest that they are a distinct group of colorectal cancers.

PMID- 12502212
TI  - Gut barrier permeability, reticuloendothelial system function and protease
      inhibitor levels following intestinal ischaemia and reperfusion--effects of
      pretreatment with N-acetyl-L-cysteine and indomethacin.
AB  - BACKGROUND: Pathophysiological mechanisms and ways to intervene on intestinal
      barrier dysfunction following small intestinal ischaemia and prolonged
      reperfusion are still not fully clarified. AIMS: To evaluate the effect of oxygen
      free radical and prostaglandin inhibition on intestinal barrier injury following
      intestinal ischaemia/reperfusion. METHODS: Endothelial and epithelial barrier
      permeability was evaluated by clearance of radiolabelled albumin. Parameters
      included 125I-Escherichia coli uptake rate index, host reticuloendothelial system
      function and organ distribution, as well as protease inhibitor and proenzyme
      activities in rats subjected to small intestinal ischaemia for 40 minutes
      followed by 12 hours reperfusion (ischaemia/reperfusion), pretreated with N
      acetyl-L-cysteine or indomethacin. RESULTS: Following ischaemia/reperfusion,
      endothelial and epithelial permeability increased, reticuloendothelial system
      activation occurred and plasma protease inhibitors were consumed. N-acetyl-L
      cysteine pretreatment resulted in improved endothelial and epithelial barrier
      integrity, a decrease in protease inhibitor consumption and less pronounced
      reticuloendothelial system activation. Pretreatment with indomethacin was not
      effective. CONCLUSION: Oxygen free radicals seem to play an important role in the
      development of intestinal barrier impairment following ischaemia/reperfusion. N
      acetyl-L-cystine may be a potential agent for preventing ischaemia/reperfusion
      damage.

PMID- 12502213
TI  - Prevalence and genomic variability of transfusion transmitted virus in Italian
      cryptogenic chronic liver disease and healthy blood donors.
AB  - BACKGROUND: Infection with transfusion transmitted virus, a new member of the
      Parvoviridae family, has been found in patients both with chronic and fulminant
      post-transfusion cryptogenic hepatitis. AIM: To evaluate the prevalence and
      clinical impact of transfusion transmitted virus infection in Italy. PATIENTS AND
      METHODS: Studies were carried out on 256 patients and control subjects from three
      centres from Northern, Central and Southern Italy (92 nonA-nonC chronic
      hepatitis, 10 acute non fulminant cryptogenic hepatitis, 41 hepatitis C virus
      related chronic hepatitis and 113 blood donors). Serum transfusion transmitted
      virus was detected by nested polymerase chain reaction using two overlapping sets
      of primers. RESULTS: A total of 52 of the 92 patients (54.3%) with chronic
      cryptogenic liver disease and 17 of the 41 hepatitis C virus chronic hepatitis
      patients (41.4%) were transfusion transmitted virus-DNA positive. Transfusion
      transmitted virus co-infection in hepatitis C virus patients was not associated
      with either a higher severity of liver histology or higher alanine transaminase
      levels or signs of cholestasis, transfusion transmitted virus was found in 48 out
      of 113 (42.4%) blood donors. In the majority of samples, transfusion transmitted
      virus DNA was detected with only one of the two sets of primers used. Genotyping
      and phylogenetic analysis performed on 21 randomly selected viral isolates showed
      the presence of both type 1 and type 2 transfusion transmitted virus and allowed
      identification of two isolates with high homology to genotype 6, described, so
      far, mostly in Japan. CONCLUSIONS: Transfusion transmitted virus type 1 and 2
      infection is common among blood donors and patients with liver disease in Italy.
      The pathogenic potential of transfusion transmitted virus type 1 and 2 in nonA
      nonC hepatitis patients is unlikely but further studies are needed to evaluate
      the epidemiological and clinical impact of other transfusion transmitted virus
      subtypes.

PMID- 12502214
TI  - Morphological and demographic associations of biliary symptoms in subjects with
      gallstones: findings from a population-based survey in Rosario, Argentina.
AB  - BACKGROUND: Gallstone disease is a frequently encountered disorder in subjects
      living in Rosario. The reasons for the presence or absence of symptoms are
      unknown. AIMS: To determine associations between biliary symptoms and
      ultrasonographic features of gallbladder and gallstones. SUBJECTS: A random study
      was conducted on 1,173 subjects, inhabitants of 20 years and older, in the city
      of Rosario, Argentina. METHODS: High-resolution abdominal ultrasound examinations
      were performed. Biliary pain was defined based on previously published
      definitions. RESULTS: Gallstones were found in 149 subjects (101 female, 48 male)
      of whom 51% of females and 35% of males with cholelithiasis were symptomatic.
      Mean age was 53 years in symptomatic and 55 in asymptomatic subjects. Gallbladder
      size was normal in 97% of symptomatic and in 96% of the asymptomatic
      participants. There were no significant differences between the groups as far as
      concerns size and gallstone number. Impacted stones were observed in 10% of
      symptomatic and in none of the asymptomatic subjects (p<0.01). CONCLUSIONS:
      Subjects' age and gender, gallstones size and number, as well as ultrasonographic
      features of gallbladder and biliary tract did not differ significantly between
      symptomatic and asymptomatic subjects. Only impacted stones were significantly
      more frequent in symptomatic subjects.

PMID- 12502215
TI  - Role of endoscopic retrograde cholangiopancreatography in the diagnosis and
      treatment of biliary tract complications after orthotopic liver transplantation.
AB  - BACKGROUND: Biliary complications are a major drawback of liver transplantation.
      AIM: To analyse, in a single centre, experience in endoscopic diagnosis and
      management of biliary complications after liver transplantation. PATIENTS: A
      total of 147 consecutive liver transplantations performed on 132 patients over a
      5-year period. METHODS: Evaluation of the incidence and type of biliary-related
      complications and analysis of their diagnosis and endoscopic treatment by
      cholangiopancreatography in terms of success of the endoscopic approach,
      conversion to surgery and long-term patient and graft survival. RESULTS:
      Endoscopic retrograde cholangiopancreatography was performed on 30 patients
      (23%). Overall incidence of biliary complications as confirmed by endoscopic
      retrograde cholangiopancreatography was 17% (25 cases). Endoscopic retrograde
      cholangiopancreatography was negative in 5 cases (16%). Biliary complications
      were successfully treated by endoscopy in 84% of cases (21 out of 25 patients); 4
      cases (16%) required a surgical approach (2 choledochojejunostomy, 2
      retransplantation) due to failure to correct the problem endoscopically. Stenoses
      and biliary sludge associated with retained internal stent were almost always
      successfully managed by endoscopic retrograde cholangiopancreatography, while
      anastomotic leakage more frequently required a surgical approach. CONCLUSIONS:
      Endoscopic retrograde cholangiopancreatography is a safe and effective approach
      for diagnosis and treatment of biliary-related complications after liver
      transplantation thereby reducing morbidity and mortality related to re-operation
      which is, however, required in selected cases.

PMID- 12502216
TI  - Endoscopic treatment of extrahepatic bile duct strictures in patients with portal
      biliopathy carries a high risk of haemobilia: report of 3 cases.
AB  - Extrahepatic portal venous obstruction can be associated with bile duct
      abnormalities, the entity being called portal biliopathy. Three cases are
      reported of extrahepatic bile duct strictures in patients with portal biliopathy
      who developed haemobilia during endotherapy. Although endoscopic therapy with
      stent placement can be successful in patients with portal biliopathy and could
      also lead to permanent stricture resolution, procedure-related haemobilia is not
      as uncommon as previously held. Shunt surgery could be a better option in fit
      patients, since it could provide definitive treatment in a young patient with an
      otherwise normal life expectancy.

PMID- 12502217
TI  - Update on ascites and hepatorenal syndrome.
AB  - Ascites is the most common complication occurring during liver cirrhosis. Even if
      a significant decrease in renal clearance may be observed in the first step of
      chronic active liver disease, renal impairment, at times complicated by the
      typical signs of hepatorenal syndrome, occurs only in patients with ascites,
      especially when tense and refractory. Experimental and clinical data seem to
      suggest a primary sodium and water retention in the pathogenesis of ascites, in
      the presence of an intrahepatic increase of hydrostatic pressure, which, by
      itself, physiologically occurs during digestion. Abnormal sodium and water
      handling leads to plasma volume expansion, followed by decreased peripheral
      vascular resistance and increased cardiac output. This second step is in
      agreement with the peripheral arterial vasodilation hypothesis, depicted by an
      increase in total blood volume, but with a decreased effective arterial blood
      volume. This discrepancy leads to the activation of the sympathetic nervous and
      renin-angiotensin-aldosterone systems associated with the progressive activation
      of the renal autacoid systems, especially, that of the arachidonic acid. During
      advanced cirrhosis, renal impairment becomes more sustained and renal autacoid
      vasodilating substances are less available, possibly due to a progressive
      exhaustion of these systems. At the same time ascites becomes refractory inasmuch
      as it is no longer responsive to diuretic treatment. Various pathogenetic
      mechanisms leading to refractory ascites are mentioned. Finally, several
      treatment approaches to overcome the reduced effectiveness of diuretic therapy
      are cited. Paracentesis, together with simultaneous administration of human
      albumin or other plasma expanders is the main common approach to treat refractory
      ascites and to avoid a further decrease in renal failure. Other effective tools
      are: administration of terlipressin together with albumin, implantation of the Le
      Veen shunt, surgical porto-systemic shunting or transjugular intrahepatic
      portosystemic stent-shunt, or orthotopic liver transplantation, according to the
      conditions of the individual patient.

PMID- 12502218
TI  - The rise and fall in primary liver cancer mortality in Italy.

PMID- 12502219
TI  - The rise and fall in primary liver cancer mortality in Italy.

PMID- 12502220
TI  - Spontaneous remission of autoimmune hepatitis during pregnancy.

PMID- 12502221
TI  - Silk suture promotes colon cancer in an experimental carcinogenic model.

PMID- 12502222
TI  - Characterization of von Willebrand factor interaction with collagens in real time
      using surface plasmon resonance.
AB  - von Willebrand factor (vWf) binding to subendothelial collagens is an initial
      step in thrombus formation. We have characterized the binding of vWf multimers to
      human pepsin-digested collagen I, III, and VI using surface plasmon resonance
      (BIAcore). Based on vWf subunit molecular weight (250 KDa), normal vWf multimers
      (nvWf) purified from human cryoprecipitate, which containing the entire range of
      multimers found in normal plasma, bound to human pepsin-digested collagen III
      with an association rate of 2.88+/-0.01 x 10(5) M(-1) s(-1), a dissociation rate
      of 5.85+/-0.10 x 10(-4) s(-1) and an equilibrium dissociation constant KD of
      2.03+/-0.04 nM. These nvWf multimers bound to human pepsin-digested collagen I
      with a five fold lower binding capacity and a ten fold higher equilibrium
      dissociation constant. There was no detectable binding between the vWf multimers
      and human pepsin-digested collagen VI. The purified vWf A3 domain, vWf
      preparations enriched in either relatively small vWf (svWf) multimers or in
      unusually large vWf (ulvWf) multimers were also studied on collagen III surfaces.
      Our results demonstrate that the vWf dissociation rates are dependent on the vWf
      molecular mass and the duration of interactions. We conclude that vWf-collagen
      binding interactions involve multiple bond processes.

PMID- 12502223
TI  - Mechanical environment, donor age, and presence of endothelium interact to
      modulate porcine artery viability ex vivo.
AB  - Though ex vivo culture of arteries is a widely used model of native arteries and
      is closely aligned with efforts to generate tissue-engineered arteries, the
      effects of culture conditions on artery viability are poorly characterized. To
      investigate factors regulating long-term viability of cultured arteries, carotid
      arteries from neonatal and adolescent pigs were perfused for up to 27 days with
      steady laminar flow ranging from approximately 2% to approximately 200% of
      physiological flow rates. Arteries from neonatal animals (2 weeks old,
      approximately 5 kg) were susceptible to spontaneous progressive endothelial
      denudation followed by deterioration of the vessel wall that spread from luminal
      to abluminal regions. Subphysiological levels of flow and pressure abrogated this
      deterioration. Arteries harvested from adolescent (6 months old, approximately
      100 kg) animals maintained viability and retained structure for at least 9 days
      as assessed by normal histology, presence of intact endothelium, normal
      mitochondrial activity, and low levels of cell death and proliferation, unless
      the vessels were subjected to superphysiological levels of flow or the
      endothelium was intentionally denuded. Adolescent arteries perfused at
      subphysiological, but not physiological, flow rates maintained viability and
      normal structure for at least 27 days. These data indicate that under the
      appropriate conditions, arteries may be cultured long term but careful attention
      to the viability is merited.

PMID- 12502224
TI  - Finite and infinitesimal representations of the vasculature: ocular drug
      clearance by vascular and hydraulic effects.
AB  - New methods are presented for simulating steady-state drug concentration in
      vitreous, choroid, and sclera from an intravitreal device. Clearance by choroidal
      flow and intraocular pressure (IOP) -induced Darcy hydraulic flow are included.
      Two methods are proposed for modeling the vasculature using simple one
      dimensional models for simulating drug concentration profiles from intravitreal
      devices. The finite choroid method adds a concentration-dependent sink term to
      the convective diffusion equation, allowing for a continuous but rapid decrease
      in concentration throughout the choroid region. The infinitesimal choroid method
      uses a combination of a simple flux boundary condition and a redefinition of the
      dependent variable to account for the impact of the vascular drain by a
      discontinuous drop in concentration across the exterior vitreous boundary. This
      eliminates the need for a choroidal region, reducing finite element memory
      requirements, enabling the choroid to be made arbitrarily thin. The impact of
      permeating fluid induced by IOP on convection was examined, using hydraulic
      coefficients for ocular tissue recently made available [Xu, J. et al., Pharm.
      Res. 17:664-669 (2000)], allowing for drug efflux through the outer sclera.
      Transport becomes diffusion limited at high vascular clearance. Hydraulic flow
      restricts the range in concentration predicted in the vitreous compared to zero
      flow. Hydraulic influences for small, rapidly cleared drugs can be neglected.

PMID- 12502225
TI  - A real time QRS detection using delay-coordinate mapping for the microcontroller
      implementation.
AB  - In this article, we propose a new algorithm using the characteristics of
      reconstructed phase portraits by delay-coordinate mapping utilizing lag rotundity
      for a real-time detection of QRS complexes in ECG signals. In reconstructing
      phase portrait the mapping parameters, time delay, and mapping dimension play
      important roles in shaping of portraits drawn in a new dimensional space.
      Experimentally, the optimal mapping time delay for detection of QRS complexes
      turned out to be 20 ms. To explore the meaning of this time delay and the proper
      mapping dimension, we applied a fill factor, mutual information, and
      autocorrelation function algorithm that were generally used to analyze the
      chaotic characteristics of sampled signals. From these results, we could find the
      fact that the performance of our proposed algorithms relied mainly on the
      geometrical property such as an area of the reconstructed phase portrait. For the
      real application, we applied our algorithm for designing a small cardiac event
      recorder. This system was to record patients' ECG and R-R intervals for 1 h to
      investigate HRV characteristics of the patients who had vasovagal syncope symptom
      and for the evaluation, we implemented our algorithm in C language and applied to
      MIT/BIH arrhythmia database of 48 subjects. Our proposed algorithm achieved a
      99.58% detection rate of QRS complexes.

PMID- 12502226
TI  - Thermal model for fast simulation during magnetic resonance imaging guidance of
      radio frequency tumor ablation.
AB  - Thermal ablation of a tumor with radio frequency (rf) energy from a small probe
      inserted into the solid tumor can be accomplished with minimal invasiveness under
      guidance with magnetic resonance imaging (MRI). A theoretical study is presented
      of 3D temperature distribution dynamics in tissue with rf heating to show the
      feasibility of fast numerical solution for repeated simulations during an
      ablation procedure. Model simulations are intended to be used during an ablation
      treatment together with temperature field images obtained by MR to predict the
      effect of alternative strategies of source heating and placement. A feature of
      the model is that it incorporates a heat source term that varies with distance
      from the rf probe to avoid the need for solving electric field equations. The
      effects of perfusion and internal cooling of the rf probe on the temperature
      distribution are simulated to show the model flexibility. Using a personal
      computer (PC), numerical solution of the model equations required 10 s to 2 min
      depending on the perfusion-temperature relationship. The results show the
      feasibility of using thermal model simulations in an iterative manner with MR
      images to help guide thermal ablation procedures in the clinical setting.

PMID- 12502227
TI  - Tissue temperature oscillations in an isolated pig kidney during surface heating.
AB  - In the present study, an isolated pig kidney was used to study tissue temperature
      oscillations due to vascular thermoregulation, frequently observed during
      hyperthermia treatments. The kidney was perfused with the distilled water pumped
      through the renal artery to simulate blood flow. When the local perfusion rate
      was increased with a time delay, temperature oscillations were observed in the
      kidney as its surface temperature raised linearly with time in a water bath. The
      magnitude of tissue temperature decreased as the flow rate increased during the
      surface heating. A 3D transient model was developed to predict the temperature
      oscillations, which was validated by the measurements. Using the model,
      relationships of the changes in perfusion rate and heating rate with temperature
      oscillations were investigated. It was found that the heating rate, and the
      magnitude and time delay of the flow response to the temperature elevation, each
      significantly affected tissue temperature oscillations. The magnitude of
      oscillation was primarily determined by the spatial gradient of temperature,
      while the oscillation type depended on the change of flow rate and the time
      delay. In conclusion, to accurately predict and control the tissue temperature
      distribution during hyperthermia treatment, understanding of the local perfusion
      change with respect to tissue temperature is essential.

PMID- 12502228
TI  - Induced current impedance technique for monitoring brain cryosurgery in a two
      dimensional model of the head.
AB  - A fast and robust finite volume solver of the two-dimensional induced current
      electrical impedance forward problem was developed. The numerical solver was
      validated by comparison with an existing analytical solution for a symmetrical
      geometry case, showing an accuracy of 0.07%. The solver was used to theoretically
      examine the sensitivity of the induced current impedance technique for the
      medical procedure of monitoring brain cryosurgery. The simulation was performed
      using a two-dimensional approximation of otherwise realistic geometry model of
      the head with different ice-ball sizes, simulating the expansion of the frozen
      lesion. The sensitivity of the scalp potential to the ice-ball size was found to
      be 53 x 10(-4) (relative scalp potential mm(-2)).

PMID- 12502229
TI  - Distributed modeling of diffusive solute transport in peritoneal dialysis.
AB  - The diffusive transport between blood and an ex-tissue medium (dialysis fluid) is
      evaluated using a mathematical model that takes into account the
      (quasicontinuous) distribution of capillaries within the tissue at various
      distances from the tissue surface, and includes diffusive-convective transport
      through the capillary wall and lymphatic absorption from the tissue. General
      formulas for solute penetration depth, lambda, and for the diffusive mass
      transport coefficient for the transport between blood and dialysis fluid, K(BD),
      are provided in terms of local transport coefficients for capillary wall, tissue,
      and lymphatic absorption. For pure diffusive transport between blood and dialysis
      fluid and thick tissue layers (i.e., if the solute penetration depth is much
      lower than the tissue thickness) these formulas yield previously known
      expressions. It is shown that apparent tissue layers, with widths lambdaTBL and
      lambdaT, respectively, may be defined according to the values of local transport
      parameters in such a way that K(BD) is equal to the solute clearance K(TBL) from
      the tissue by blood and lymph for a layer with width lambdaTBL or to the solute
      clearance K(T) from blood to dialysate by diffusion through the tissue layer with
      width lambdaT. For tissue layers with width much higher than the penetration
      depth: lambdaT approximately = lambdaTBL approximately = lambda. These
      characteristic width lengths depend on the transport parameters (and thus on the
      size) of solutes. Effective blood flow, which may be related to the exchange of
      the solute between blood and dialysate, is defined using an analogy to the
      extraction/absorption coefficients for blood-tissue exchange. Various
      approximations for the distributed model formula for diffusive mass transport
      coefficient (K(BD)) are possible. The appropriate range for their application is
      obtained from the general formula.

PMID- 12502230
TI  - Modulation of rod photoreceptor potassium Kx current by divalent cations.
AB  - Similarities between photoreceptor Kx channels and EAG and KCNQ channels suggest
      that the Kx channel may be related to one or both of these families of potassium
      channels. To provide a basis for further comparison of these channels, as well as
      to reveal the role of zinc (endogenously present in photoreceptors) in Kx channel
      modulation, we studied the effects of divalent cations on activation and kinetic
      properties of the noninactivating potassium current, I(Kx), in salamander rod
      photoreceptors. We found that divalent cations slowed the activation of I(Kx) and
      shifted its activation curve to positive potentials, effects attributable to
      surface charge screening. The effect of zinc on I(Kx) kinetics was considerably
      stronger than that expected from the activation curve shift alone. None of the
      divalent ions studied changed the monoexponential nature of I(Kx) activation. A
      simple model of a rod photoreceptor was created using NEURON software. In the
      model, zinc accelerated and sharpened the light response, broadening the
      frequency response of rod photoreceptors. Our results show that although the
      overall effects of divalent cations are in part due to surface charge screening
      effects, zinc also induced a specific change in I(Kx) activation kinetics, and
      this action profoundly alters rod response properties.

PMID- 12502231
TI  - A new approach to closed-loop linear system identification via a vector
      autoregressive model.
AB  - A new vector autoregressive (VAR) model algorithm is developed for closed-loop
      identification. The new VAR approach is an extension of a recently developed
      algorithm, named the optimal parameter search (OPS), thus, we call the new
      technique VOPS, for vector OPS. Monte Carlo simulations of closed-loop systems
      were performed to compare the performance of VOPS to the widely utilized vector
      least squares (VLS) and vector fast orthogonal search (VFOS) approaches. In
      addition, we examined the effect on parameter estimates obtained via open-loop
      identification techniques, when using data from closed-loop systems. Comparative
      results show that both the VOPS and VFOS algorithms produce far more accurate
      parameter estimates than does the VLS. Furthermore, open-loop identification via
      univariate OPS and to a lesser extent univariate FOS for closed-loop systems,
      does not adversely affect the accuracy of the parameter estimates. An open-loop
      identification via the univariate least-squares method for closed-loop systems
      showed the most deleterious effect on the accuracy of the parameter estimates. In
      addition to developing the VOPS algorithm, we also developed approaches termed
      constrained OPS (COPS) and constrained FOS (CFOS). For closed-loop systems
      considered in this paper, both COPS and CFOS resulted in more accurate parameter
      estimates (less biased and more efficient) than did VLS, VFOS, and VOPS.

PMID- 12502232
TI  - Apportionment in asbestos-related disease for purposes of compensation.
AB  - Workers' compensation systems attempt to evaluate claims for occupational disease
      on an individual basis using the best guidelines available to them. This may be
      difficult when there is more than one risk factor associated with the outcome,
      such as asbestos and cigarette smoking, and the occupational exposures is not
      clearly responsible for the disease. Apportionment is an approach that involves
      an assessment of the relative contribution of work-related exposures to the risk
      of the disease or to the final impairment that arises for the disease. This
      article discusses the concept of apportionment and applies it to asbestos
      associated disease. Lung cancer is not subject to a simple tradeoff between
      asbestos exposure and smoking because of the powerful biological interaction
      between the two exposures. Among nonsmokers, lung cancer is sufficiently rare
      that an association with asbestos can be assumed if exposure has occurred.
      Available data suggest that asbestos exposure almost invariably contributes to
      risk among smokers to the extent that a relationship to work can be presumed.
      Thus, comparisons of magnitude of risk between smokers and nonsmokers are
      irrelevant for this purpose. Indicators of sufficient exposure to cause lung
      cancer are useful for purposes of establishing eligibility and screening claims.
      These may include a chest film classified by the ILO system as 1/0 or greater
      (although 0/1 does not rule out an association) or a history of exposure roughly
      equal to or greater than 40 fibres/cm3 x y. (In Germany, 25 fibres/cm3 x y is
      used.) The mere presence of pleural plaques is not sufficient. Mesothelioma is
      almost always associated with asbestos exposure and the association should be
      considered presumed until proven otherwise in the individual case. These are
      situations in which only risk of a disease is apportioned because the impairment
      would be the same given the disease whatever the cause. Asbestosis, if the
      diagnosis is correct, is by definition an occupational disease unless there is
      some source of massive environmental exposure; it is always presumed to be work
      related unless proven otherwise. Chronic obstructive airways disease (COAD)
      accompanies asbestosis but may also occur in the context of minimal parenchymal
      fibrosis and may contribute to accelerated loss of pulmonary function. In some
      patients, particularly those with smoking-induced emphysema, this may contribute
      significantly to functional impairment. An exposure history of 10 fibre x years
      is suggested as the minimum associated with a demonstrable effect on impairment,
      given available data. Equity issues associated with apportionment include the
      different criteria that must be applied to different disorders for apportionment
      to work, the management of future risk (eg. risk of lung cancer for those who
      have asbestosis), and the narrow range in which apportionment is really useful in
      asbestos-associated disorders. Apportionment, attractive as it may be as an
      approach to the adjudication of asbestos-related disease, is difficult to apply
      in practice. Even so, these models may serve as a general guide to the assessment
      of asbestos-related disease outcomes for purposes of compensation.

PMID- 12502233
TI  - Influence of frequency on difference thresholds for magnitude of vertical
      sinusoidal whole-body vibration.
AB  - Differences in vibration magnitude required for a human subject to differentiate
      whole-body vertical sinusoidal vibrations, difference thresholds for amplitude of
      sinusoidal vibration, have been determined at a vibration magnitude of 0.7 m/s2
      r.m.s. at five octave band center frequencies from 4 to 63 Hz and at 80 Hz. The
      median difference thresholds of 16 male subjects seated on a flat rigid seat were
      found between 0.037 and 0.046 m/s2 r.m.s. at the frequencies used in this study.
      The subjects tended to be more sensitive to the change in vibration magnitude at
      4 Hz than at 16, 31.5 and 63 Hz and less sensitive to the magnitude difference at
      31.5 Hz than at 4, 8 and 80 Hz. The median relative difference thresholds,
      Weber's ratios, varied from 5.2% to 6.5% which were lower compared to the
      relative difference thresholds determined in the previous studies at frequencies
      where comparable data were available. The causes of the difference in the
      relative difference thresholds observed between this study and previous studies
      may include the difference in the psychophysical method used to determine the
      difference threshold.

PMID- 12502234
TI  - Effects of electromagnetic radiation (bright light, extremely low-frequency
      magnetic fields, infrared radiation) on the circadian rhythm of melatonin
      synthesis, rectal temperature, and heart rate.
AB  - Electromagnetic spectra reduce melatonin production and delay the nadirs of
      rectal temperature and heart rate. Seven healthy men (16-22 yrs) completed 4
      permuted sessions. The control session consisted of a 24-hours bedrest at < 30
      lux, 18 degrees C, and < 50 dBA. In the experimental sessions, either light (1500
      lux), magnetic field (16.7 Hz, 0.2 mT), or infrared radiation (65 degrees C) was
      applied from 5 pm to 1 am. Salivary melatonin level was determined hourly, rectal
      temperature and heart rate were continuously recorded. Melatonin synthesis was
      completely suppressed by light but resumed thereafter. The nadirs of rectal
      temperature and heart rate were delayed. The magnetic field had no effect.
      Infrared radiation elevated rectal temperature and heart rate. Only bright light
      affected the circadian rhythms of melatonin synthesis, rectal temperature, and
      heart rate, however, differently thus causing a dissociation, which might enhance
      the adverse effects of shiftwork in the long run.

PMID- 12502235
TI  - Correlations between workplace protection factors and fit factors for filtering
      facepieces in the welding workplace.
AB  - Workplace protection factor (WPF) means a measure of the actual protection of
      respirator provided in the workplace when correctly worn. While fit factor (FF)
      represents a quantitative measure of the fit of a particular respirator to an
      individual and it is determined in the laboratory. To evaluate the relationship
      between WPF and FF is very important since FF may or may not be taken advantage
      of estimating WPF. Outside and inside Fe concentrations for three brand N95
      filtering facepieces were collected on 14 workers/three respirator combinations
      in the welding workplace. The WPF measurements on the samples of the three
      respirator brands worn by 14 workers were observed to range from 2.2 to 132.9
      with a geometric mean of 15.9 and a geometric standard deviation of 2.63.
      Respirator performances as measured by the WPF differed significantly among
      different respirator brands (p<0.05). In this study, correlations were found
      between the WPF measurements and the FF data for all samples of the three
      respirators (R2=0.38). The percentage of Fe particles having a smaller fraction
      than 1.1 microm diameter was observed as 71.6% of the total.

PMID- 12502236
TI  - Increased medication use in a community environmentally exposed to chemicals.
AB  - An epidemiological health study compared the health status of residents of a town
      exposed to an accidental Catacarb chemical release from an adjacent oil refinery,
      with the health status of demographically similar residents of an unexposed town
      in the region. Few studies of Catacarb's effects on humans exist; however, animal
      studies have shown it to be a respiratory, gastro-intestinal, dermatological and
      visual irritant. As part of the study, health questionnaires assessing pre- and
      post exposure symptoms, illnesses and medication use were mailed to residents in
      both towns. Medication use is sometimes reported to be a more objective and
      reliable measure of health outcomes. The current paper compared medication use of
      exposed and unexposed residents. Significant increases after exposure were found
      in the use of the following medications: antacid, asthma medication, cough and
      cold medication, eye medication, headache medication and sleep medication. These
      increases were consistent with reported symptoms, albeit of greater magnitude; no
      increase in medication use for other illnesses was reported. Medication use in
      this sample was consistent with patients' report of symptoms and may be a better
      measure of outcome.

PMID- 12502237
TI  - Reproductive toxicity of carbofuran to the female mice: effects on estrous cycle
      and follicles.
AB  - Carbofuran, a systemic N-methyl carbamate pesticide was orally administered with
      the doses of 0.4, 0.7, 1 and 1.3 mg/kg body weight/day to normal virgin female
      Swiss albino mice for 30 days. The vaginal smear and body weight of mice were
      recorded daily and mice were sacrificed on the 31st day. Estrous cycle was
      effected by showing a significant decrease in the number of estrous cycle and the
      duration of each phases of estrous cycle with concomitant significant increase in
      the diestrus phase in 1 and 1.3 mg/kg/d carbofuran treatment when compared with
      that of control mice. There was a significant decrease in the number of healthy
      follicles and a significant increase in the number of atretic follicles in 1 and
      1.3 mg/kg/d treated groups when compared with the control. The histologic
      observations of the ovary revealed the presence of less number of healthy
      follicles and more number of atretic follicles in high dose of carbofuran treated
      mice. There was a dose dependent decrease in the body weight. The ovary weight
      was also decreased significantly in 1.3 mg/kg/d carbofuran treatment. There were
      no significant change in the weight of the organs such as uterus, kidney,
      adrenal, liver, spleen, thymus and thyroid. These observed effects of carbofuran
      on the estrous cycle and follicles may be due to a direct effect on the ovary or
      the hypothalamo-hypophysial ovarian axis causing hormonal imbalance.

PMID- 12502238
TI  - Thermotactile perception thresholds measurement conditions.
AB  - The purpose of this paper is to investigate the effects of posture, push force
      and rate of temperature change on thermotactile thresholds and to clarify
      suitable measuring conditions for Japanese people. Thermotactile (warm and cold)
      thresholds on the right middle finger were measured with an HVLab thermal
      aesthesiometer. Subjects were eight healthy male Japanese students. The effects
      of posture in measurement were examined in the posture of a straight hand and
      forearm placed on a support, the same posture without a support, and the fingers
      and hand flexed at the wrist with the elbow placed on a desk. The finger push
      force applied to the applicator of the thermal aesthesiometer was controlled at a
      0.5, 1.0, 2.0 and 3.0 N. The applicator temperature was changed to 0.5, 1.0, 1.5,
      2.0 and 2.5 degrees C/s. After each measurement, subjects were asked about
      comfort under the measuring conditions. Three series of experiments were
      conducted on different days to evaluate repeatability. Repeated measures ANOVA
      showed that warm thresholds were affected by the push force and the rate of
      temperature change and that cold thresholds were influenced by posture and push
      force. The comfort assessment indicated that the measurement posture of a
      straight hand and forearm laid on a support was the most comfortable for the
      subjects. Relatively high repeatability was obtained under measurement conditions
      of a 1 degrees C/s temperature change rate and a 0.5 N push force. Measurement
      posture, push force and rate of temperature change can affect the thermal
      threshold. Judging from the repeatability, a push force of 0.5 N and a
      temperature change of 1.0 degrees C/s in the posture with the straight hand and
      forearm laid on a support are recommended for warm and cold threshold
      measurements.

PMID- 12502239
TI  - Effects of pH and temperature on force and stiffness of skeletal muscle fibers
      during contraction and relaxation in relation to musculoskeletal disorders.
AB  - Effects of low pH (6.0, 6.5) were studied at three temperatures (5, 15, 25
      degrees C) on the isometric force and stiffness of glycerinated muscle fibers
      dissected from soleus (type I) and psoas (type IIX) muscles of the Japanese white
      rabbit. It was observed that the maximum force and stiffness declined as pH
      decreased, the extent of which was diminished by an increase in temperature in
      both muscle types. The pH-induced changes in force were greater than those in the
      stiffness for both muscle types: at 5 degrees C, the psoas showed greater change
      in stiffness than the soleus. As the pH of the contracting solution decreased,
      the time to peak stiffness decreased and the time to relaxation increased in both
      muscle types. At pH 6.0, the latter was significantly longer than the former. The
      force-stiffness curves indicated that, when pH decreased, force increased as fast
      as stiffness during contraction and force declined faster than stiffness during
      relaxation. The results suggested that one of the causes of muscle injury during
      hard muscular work could be the longer relaxation time in an acidic solution.

PMID- 12502240
TI  - Involvement of caspase 3 mediated apoptosis in hematopoietic cytotoxicity of
      metabolites of ethylene glycol monomethyl ether.
AB  - The hematopoietic toxicity of ethylene glycol monomethyl ether (EGME) and its
      metabolites, methoxy acetaldehyde (MALD) and methoxyacetic acid (MAA), was
      analyzed using human bone marrow cells from a lymphoma patient without bone
      marrow involvement and a human leukemia cell line, HL60. After 24-hour
      incubation, the concentrations of 50 percent inhibition (IC50) of human
      hematopoietic progenitor cells with MALD or MAA were 3 mM and 3.9 mM,
      respectively, and EGME (10 mM or more) did not show any cytotoxicity. IC50 (after
      48-hour exposure) of MALD and MAA on HL60 cells were 2.45 mM and 5.6 mM,
      respectively, suggesting that both hematopoietic progenitor cells and HL60 have a
      similar sensitivity. DNA ladder formation, a characteristics of apoptosis, was
      observed in MALD- or MAA-treated HL60 cells, but not in EGME-treated samples.
      Caspase-3 enzyme activity, the effector of the apoptotic process, was greatly
      enhanced with MALD treatment. The inhibitor of caspase-3 repressed cell death
      induced with MALD as well as MAA.

PMID- 12502241
TI  - Effects of in utero and lactational exposure to bisphenol A on somatic growth and
      anogenital distance in F1 rat offspring.
AB  - Bisphenol A (BPA), a xenoestrogen, has been reported to mimic the actions of
      estrogen or to affect the endocrine glands in vivo and in vitro. In this study,
      we examined whether in utero and lactational exposure to BPA altered the somatic
      growth and anogenital distance (AGD) of F1 offspring (1, 3, and 9 weeks of age)
      in vivo in rats. Dams were orally administered with various doses of BPA (0, 4,
      or 40 mg/kg body weight (BW)/day) from gestation day (GD) 6 through postnatal day
      (PND) 20. There were no significant changes in body weight, liver weight, kidneys
      weight, testes weight, AGD, the ratio of AGD to BW, or the ratio of AGD to the
      cube root of BW in BPA exposed pups compared to the vehicle-exposed control. This
      suggests that prenatal and postnatal exposure (indirect exposure) to BPA (4-40
      mg/kg/day, GD 6-PND 20) does not affect on somatic growth or AGD of F1 generation
      of male and female rats.

PMID- 12502242
TI  - Concurrent malignant mesothelioma of the pleura and hepatocellular carcinoma in
      the same patient: a report of five cases.
AB  - Five cases are reported in which malignant mesothelioma of the pleura and
      hepatocellular carcinoma co-existed in the same patient. The group included four
      men and one woman, aged between 58 and 86 years. The diagnosis was established at
      necropsy. In one case the association was clinically suspected. All mesotheliomas
      were asbestos-related. Liver cirrhosis co-existed in four cases, two of them
      positive for HCV markers. A lot of elements suggest that the above association is
      not a fortuitous coincidence. In particular, asbestos could favour liver
      cancerogenesis by inducing immune impairment.

PMID- 12502243
TI  - Phylogenetic analysis of North American Elymus and the monogenomic Triticeae
      (Poaceae) using three chloroplast DNA data sets.
AB  - Although the monogenomic genera of the Triticeae have been analyzed in numerous
      biosystematic studies, the allopolyploid genera have not been as extensively
      studied within a phylogenetic framework. We focus on North American species of
      Elymus, which, under the current genomic system of classification, are almost all
      allotetraploid, combining the St genome of Pseudoroegneria with the H genome of
      Hordeum. We analyze new and previously published chloroplast DNA data from Elymus
      and from most of the monogenomic genera of the Triticeae in an attempt to
      identify the maternal genome donor of Elymus. We also present a cpDNA phylogeny
      for the monogenomic genera that includes more data than, and thus builds on,
      those previously published. The chloroplast DNA data indicate that
      Pseudoroegneria is the maternal genome donor to all but one of the Elymus
      individuals. There is little divergence among the Elymus and Pseudoroegneria
      chloroplast genomes, and as a group, they show little divergence from the rest of
      the Triticeae. Within the monogenomic Triticeae, the problematic group Thinopyrum
      is resolved as monophyletic on the chloroplast DNA tree. At the intergeneric
      level, the data reveal several deeper-level relationships that were not resolved
      by previous cpDNA trees.

PMID- 12502244
TI  - Comparative linkage map of the Solanum lycopersicoides and S. sitiens genomes and
      their differentiation from tomato.
AB  - The wild nightshades Solanum lycopersicoides and Solanum sitiens are closely
      affiliated with the tomatoes (Lycopersicon spp.). Intergeneric hybridization with
      cultivated tomato (Lycopersicon esculentum) is impeded by strong reproductive
      barriers including hybrid sterility and suppressed recombination. Conservation of
      genome structure between these nightshades and tomato was studied by construction
      of a genetic map from F2 S. sitiens x S. lycopersicoides and comparison with
      existing maps of tomato. Owing to self-incompatibility of the F1, two hybrid
      plants were crossed to obtain a population of 82 F2 individuals. Using 166
      previously mapped RFLP markers and 5 restriction enzymes, 101 loci polymorphic in
      the S. sitiens x S. lycopersicoides population were identified. Analysis of
      linkage between the markers resulted in a map with 12 linkage groups covering
      1192 cM and one unlinked marker. Recombination rates were similar to those
      observed in tomato; however, significant segregation distortion was observed for
      markers on 7 out of the 12 chromosomes. All chromosomes were colinear with the
      tomato map, except for chromosome 10, where a paracentric inversion on the long
      arm was detected. In this region, S. sitiens and S. lycopersicoides share the
      same chromosomal configuration previously reported for potato (S. tuberosum) and
      pepper (Capsicum), suggesting that of tomato is derived. The 10L inversion
      explains the lack of recombination detected among homeologous chromosomes of
      intergeneric hybrids in this region. On this basis, we recognize two principle
      genomes, designated L for the Lycopersicon spp., and S for S. lycopersicoides and
      S. sitiens, the first examples of structural differentiation between tomato and
      its cross-compatible wild relatives.

PMID- 12502245
TI  - Identification of putative genes in bean (Phaseolus vulgaris) genomic (Bng) RFLP
      clones and their conversion to STSs.
AB  - A set of 79 previously mapped bean (Phaseolus vulgaris) genomic (Bng) clones were
      partially sequenced. BLAST database searches detected homologies between 59 of
      these clones and genes from a variety of plants, especially Arabidopsis thaliana.
      Some matches in the database to the Bng clones included a putative P-glycoprotein
      ABC transporter from Arabidopsis, an early nodulin-binding protein (ENBPI) from
      Medicago truncatula, a lon-protease protein from spinach, a branched-chain amino
      acid aminotransferase from Arabidopsis, and a vacuolar sorting receptor (BP-80)
      from Pisum sativum. Additional matches were found for genes involved in
      isoprenoid biosynthesis, sulfur metabolism, proline biosynthesis, and floral
      development. Sequence tagged site (STSs) were produced for 16 of the clones, 2 of
      which contain simple sequence repeats (SSRs). Polymorphisms were detected for six
      of the STSs.

PMID- 12502246
TI  - Genetic factors controlling white gene expression of the transposon A(R) 4-24 at
      a telomere in Drosophila melanogaster.
AB  - The position effect of the AR 4-24 P[white, rosy] transposon was studied at
      cytological position 60F. Three copies of the transposon (within approximately 50
      kb region) resulted in a spatially restricted pattern of white variegation. This
      pattern was modified by temperature and by removal of the Y chromosome,
      suggesting that it was due to classical heterochromatin-induced position effect
      variegation (PEV). In contrast with classical PEV, extra dose of the
      heterochromatin protein 1 (HP1) suppressed white variegation and one dose
      enhanced it. The effect of Pc-G, trx-G, and other PEV suppressors was also
      tested. It was found that E(Pc)1, TrlR85, and mutations of Su(z)2C relieve A(R) 4
      24-silencing and z1 enhances it. To explain the results obtained with these
      modifiers, it is proposed that PEV and telomeric position effect can counteract
      each other at this particular cytological site.

PMID- 12502247
TI  - Mutations in wheat showing altered field resistance to yellow and brown rust.
AB  - Intensive screening of a small population of mutagenised wheat lines revealed a
      large number of lines with altered resistance to both yellow and brown rust. The
      parental cultivar Guardian has an intermediate level of adult plant resistance to
      this disease; mutants were therefore isolated that showed either enhanced
      resistance or enhanced susceptibility to yellow rust. Seven lines were identified
      that gave an altered yellow rust disease phenotype as adult plants under both
      field and greenhouse conditions. Simultaneous field testing for brown rust
      infection identified two of these lines as having increased resistance to brown
      rust.

PMID- 12502248
TI  - Heterologous nuclear and chloroplast microsatellite amplification and variation
      in tea, Camellia sinensis.
AB  - The advantage of the cross transferability of heterologous chloroplast and
      nuclear microsatellite primers was taken to detect polymorphism among 24 tea
      (Camellia sinensis (L.) O. Kuntze) genotypes, including both the assamica and the
      sinensis varieties. Primer information was obtained from the closely related
      Camellia japonica species for four nuclear microsatellites, and from Nicotiana
      tabaccum for seven universal chloroplast microsatellites. All of the nuclear
      microsatellite loci tested generated an expected DNA fragment in tea, revealing
      between three and five alleles per locus. Four out of the seven chloroplast
      microsatellites primers amplified positively, and of these only one was
      polymorphic with three alleles, which is in agreement with the conserved nature
      of chloroplast microsatellites at the intraspecific level. A factorial
      correspondence analysis carried out on all genotypes and nuclear microsatellite
      alleles separated the assamica and sinensis genotypes into two groups, thus
      demonstrating the value of these markers in establishing the genetic relationship
      between tea varieties. Genetic diversity measured with nuclear microsatellites
      was higher than that measured with other types of molecular markers, offering
      prospects for their use in fingerprinting, mapping, and population genetic
      studies, whereas polymorphisms detected at a cpSSR locus will allow the
      determination of plastid inheritance in the species.

PMID- 12502249
TI  - An isoleucine to leucine mutation in acetyl-CoA carboxylase confers herbicide
      resistance in wild oat.
AB  - Wild oat (Avena fatua L.) populations resistant to herbicides that inhibit acetyl
      CoA carboxylase (ACCase; EC 6.4.1.2) represent an increasingly important weed
      control problem. The objective of this study was to determine the ACCase mutation
      responsible for herbicide resistance in a well-studied wild oat biotype (UMI). A
      2039-bp region encompassing the carboxybiotin and acetyl-CoA binding domains of
      multifunctional plastidic ACCase was analyzed. DNA sequences representing three
      plastidic ACCase gene loci were isolated from both the resistant UMI and a
      herbicide-susceptible biotype, consistent with the hexaploid nature of wild oat.
      Only one nonsynonymous point mutation was found among the resistant wild oat
      sequences, inferring an isoleucine to leucine substitution. The position of this
      substitution corresponds to residue 1769 of wheat (Triticum aestivum L.)
      plastidic ACCase (GenBank accession No. AF029895). Analysis of an F2 population
      derived from a cross between a herbicide-resistant and a susceptible biotype
      confirmed co-segregation of herbicide resistance with the mutated ACCase. We
      conclude that the isoleucine to leucine mutation is responsible for herbicide
      resistance in UMI wild oat based on a comparison of the substitution site across
      species and ACCase types. While isoleucine is conserved among plastidic ACCases
      of herbicide-susceptible grasses, leucine is found in plastidic and cytosolic
      forms of multifunctional herbicide-resistant ACCase.

PMID- 12502250
TI  - Mapping of quantitative trait loci controlling broomrape (Orobanche crenata
      Forsk.) resistance in faba bean (Vicia faba L.).
AB  - Orobanche crenata Forsk. is a root parasite that produces devastating effects on
      many crop legumes and has become a limiting factor for faba bean production in
      the Mediterranean region. The efficacy of available control methods is minimal
      and breeding for broomrape resistance remains the most promising method of
      control. Resistance seems to be scarce and complex in nature, being a
      quantitative characteristic difficult to manage in breeding programmes. To
      identify and map the QTLs (quantitative trait loci) controlling the trait, 196 F2
      plants derived from the cross between a susceptible and a resistant parent were
      analysed using isozymes, RAPD, seed protein genes, and microsatellites. F2
      derived F3 lines were studied for broomrape resistance under field conditions. Of
      the 130 marker loci segregating in the F2 population, 121 could be mapped into 16
      linkage groups. Simple interval mapping (SIM) and composite interval mapping
      (CIM) were performed using QTL Cartographer. Composite interval mapping using the
      maximum number of markers as cofactors was clearly the most efficient way to
      locate putative QTLs. Three QTLs for broomrape resistance were detected. One of
      the three QTLs explained more than 35% of the phenotypic variance, whereas the
      others accounted for 11.2 and 25.5%, respectively. This result suggests that
      broomrape resistance in faba bean can be considered a polygenic trait with major
      effects of a few single genes.

PMID- 12502251
TI  - Inheritance of microsatellite loci in the white sturgeon (Acipenser
      transmontanus).
AB  - Nine tetramer motif (GATA)n microsatellite systems were developed for use in the
      white sturgeon, Acipenser transmontanus. We report inheritance patterns for these
      nine systems, which range from one possible disomic system to tetrasomy and
      octosomy, with some systems containing null alleles. Because of the complex modes
      of inheritance underlying these systems and the highly duplicated nature of the
      genome, we propose each allele be scored as its own dominant marker, similar to
      AFLPs or RAPDs. The utility of this method is validated by the observation that
      individual alleles within a microsatellite system generally fit the expectation
      for independent transmission and fit the expected transmission frequency for
      single copy nuclear markers.

PMID- 12502252
TI  - The relationship between the dominant Additional vein mutant in Drosophila
      melanogaster and engrailed.
AB  - Additional vein (Adv) is a dominant mutation that affects the first wing vein in
      Drosophila. It also manifests a recessive lethal phenotype and is associated with
      a large inversion. Using a combination of genetic and cytogenetic techniques, we
      show that Adv interacts with engrailed (en), likely because one of the inversion
      breakpoints interferes with en function. Genetic interaction studies reveal that
      Adv is lethal in trans with various lethal alleles of en and gives an engrailed
      like wing phenotype with weak alleles of en. In situ hybridization to polytene
      chromosomes using en cDNA demonstrates that one of the inversion breakpoints lies
      within the en coding region. Although the cause of the wing phenotype is not
      determined herein, it likely is caused by the other inversion breakpoint
      interfering with a different function. The characterization of this mutation
      could expedite studies to understand what molecular events result in the Adv
      phenotype and thereby provide insight into the development of the first wing vein
      in Drosophila.

PMID- 12502253
TI  - Microsatellite DNA fingerprinting, differentiation, and genetic relationships of
      clones, cultivars, and varieties of six poplar species from three sections of the
      genus Populus.
AB  - Accurate identification of Populus clones and cultivars is essential for
      effective selection, breeding, and genetic resource management programs. The unit
      of cultivation and breeding in poplars is a clone, and individual cultivars are
      normally represented by a single clone. Microsatellite DNA markers of 10 simple
      sequence repeat loci were used for genetic fingerprinting and differentiation of
      96 clones/cultivars and varieties belonging to six Populus species (P. deltoides,
      P. nigra, P. balsamifera, P. trichocarpa, P. grandidentata, and P maximowiczii)
      from three sections of the genus. All 96 clones/cultivars could be uniquely
      fingerprinted based on their single- or multilocus microsatellite genotypes. The
      five P. grandidentata clones could be differentiated based on their single-locus
      genotypes, while six clones of P. trichocarpa and 11 clones of P. maximowiczii
      could be identified by their two-locus genotypes. Twenty clones of P. deltoides
      and 25 clones of P. nigra could be differentiated by their multilocus genotypes
      employing three loci, and 29 clones of P. balsamifera required the use of
      multilocus genotypes at five loci for their genetic fingerprinting and
      differentiation. The loci PTR3, PTR5, and PTR7 were found to be the most
      informative for genetic fingerprinting and differentiation of the clones. The
      mean number of alleles per locus ranged from 2.9 in P. trichocarpa or P.
      grandidentata to 6.0 in P. balsamifera and 11.2 in 96 clones of the six species.
      The mean number of observed genotypes per locus ranged from 2.4 in P.
      grandidentata to 7.4 in P. balsamifera and 19.6 in 96 clones of the six species.
      The mean number of unique genotypes per locus ranged from 1.3 in P. grandidentata
      to 3.9 in P. deltoides and 8.8 in 96 clones of the six species. The power of
      discrimination of the microsatellite DNA markers in the 96 clones ranged from
      0.726 for PTR4 to 0.939 for PTR7, with a mean of 0.832 over the 10 simple
      sequence repeat loci. Clones/cultivars from the same species showed higher
      microsatellite DNA similarities than the clones from the different species. A
      UPGMA cluster plot constructed from the microsatellite genotypic similarities
      separated the 96 clones into six major groups corresponding to their species.
      Populus nigra var. italica clones were genetically differentiated from the P.
      nigra var. nigra clones. Microsatellite DNA markers could be useful in genetic
      fingerprinting, identification, classification, certification, and registration
      of clones, clultivars, and varieties as well as genetic resource management and
      protection of plant breeders' rights in Populus.

PMID- 12502254
TI  - Genetic diversity in three groups of barley germplasm assessed by simple sequence
      repeats.
AB  - Genetic diversity can be measured by several criteria, including phenotype,
      pedigree, allelic diversity at marker loci, and allelic diversity at loci
      controlling phenotypes of interest. Abundance, high level of polymorphism, and
      ease of genotyping make simple sequence repeats (SSRs) an excellent molecular
      marker system for genetics diversity analyses. In this study, we used a set of
      mapped SSRs to survey three representative groups of barley germplasm: a sample
      of crop progenitor (Hordeum vulgare subsp. spontaneum) accessions, a group of
      mapping population parents, and a group of varieties and elite breeding lines.
      The objectives were to determine (i) how informative SSRs are in these three sets
      of barley germplasm resources and (ii) the utility of SSRs in classifying barley
      germplasm. A total of 687 alleles were identified at 42 SSR loci in 147
      genotypes. The number of alleles per locus ranged from 4 to 31, with an average
      of 16.3. Crop progenitors averaged 10.3 alleles per SSR locus, mapping population
      parents 8.3 alleles per SSR locus, and elite breeding lines 5.8 alleles per SSR
      locus. There were many exclusive (unique) alleles. The polymorphism information
      content values for the SSRs ranged from 0.08 to 0.94. The cluster analysis
      indicates a high level of diversity within the crop progenitors accessions and
      within the mapping population parents. It also shows a lower level of diversity
      within the elite breeding germplasm. Our results demonstrate that this set of
      SSRs was highly informative and was useful in generating a meaningful
      classification of the germplasm that we sampled. Our long-term goal is to
      determine the utility of molecular marker diversity as a tool for gene discovery
      and efficient use of germplasm.

PMID- 12502255
TI  - Rapid microsatellite analysis using discontinuous polyacrylamide gel
      electrophoresis.
AB  - A method for screening large numbers of samples for microsatellites using
      discontinuous, non-denaturing polyacrylamide gels and rapid fluorescent gel
      staining is described. Disc electrophoresis on slab gels provides high-resolution
      of PCR products. It is useful for collecting population data once microsatellite
      loci have been characterized.

PMID- 12502256
TI  - Synaptic behaviour and morphological modifications of the X and Y chromosomes
      during pachytene in three species of Ctenomys (Rodentia, Caviomorpha,
      Ctenomyidae).
AB  - Synaptic behaviour and the progression of morphological differentiation of the XY
      chromosome pair during pachytene was studied for the first time in three species
      of the South American subterranean rodents of the genus Ctenomys (tuco-tucos). In
      general, synapsis progression in the sex pair could be subdivided into four
      substages: (i) initial partial synapsis of the X and Y chromosome axes and
      beginning of the differentiation of the unsynapsed regions; (ii) complete or
      almost complete synapsis of the Y axis accompanied with morphological
      differentiation of the unsynapsed region of the X chromosome; (iii) a novel stage
      exclusive to Ctenomys perrensi consisting in a retraction of the free X axis,
      associated with the formation of a homogeneous and dense structure along the
      synaptic region, which leads to the achievement of full synapsis between sex
      chromosomes; or (iv) an increase in morphological complexity involving extreme
      splitting of the XY pair. The implications of the peculiar synaptic behaviour
      displayed by sex chromosomes in C. perrensi, a species complex highly polymorphic
      for Robertsonian translocations, are discussed in relation to both the triggering
      of the pachytene checkpoint and the avoidance of non-homologous associations
      between sex chromosomes and the asynaptic pericentromeric regions of trivalents
      in translocation heterozygotes.

PMID- 12502257
TI  - Effectiveness of selective genotyping for detection of quantitative trait loci:
      an analysis of grain and malt quality traits in three barley populations.
AB  - Marker genotype data and grain and malt quality phenotype data from three barley
      (Hordeum vulgare L.) mapping populations were used to investigate the feasibility
      of selective genotyping for detection of quantitative trait loci (QTLs). With
      selective genotyping, only individuals with high and low phenotypic values for
      the trait of interest are genotyped. Here, genotyping of 10 to 70% of each
      population (i.e., 5 to 35% in each tail of the phenotypic distribution) was
      considered. Genomic positions detected by selective genotyping were compared to
      QTL position estimates from interval mapping analysis using marker genotype data
      from the entire population. Selective genotyping reliably detected almost all of
      the mapped QTLs, often with only 10% of the population genotyped. Selective
      genotyping also detected spurious QTLs in regions of the genome where no
      significant QTL had been mapped. Even with additional genotyping to verify
      putative QTLs, the total genotyping effort for detection of QTLs for a single
      trait by selective genotyping was usually less than 30% of that required for
      conventional interval mapping. Simultaneous investigation of two or more traits
      by selective genotyping would require additional genotyping effort, but could
      still be worthwhile.

PMID- 12502258
TI  - Ribosomal DNA variation in the grasshopper, Dichroplus elongatus.
AB  - We report an RFLP analysis of ribosomal DNA variation in natural populations of
      the grasshopper, Dichroplus elongatus, previously analyzed for mitochondrial DNA
      variation. DNA samples were digested with five restriction enzymes, BamHI, EcoRI,
      HindIII, PstI, and XbaI. BamHI was the only enzyme that showed no variation. The
      remaining enzymes showed fragment size variation at both intra- and
      interpopulation levels. Stepwise regression analysis revealed that the average
      number of length variants per individual is significantly associated with
      altitude. Moreover, the same analysis indicated that the frequency of some
      restriction variants exhibits a significant regression on both geographic and
      climatic variables. The intra- and interpopulation variability of rDNA was
      analysed by Lynch's and Hedrick's similarity indices using presence or absence of
      a fragment and band intensities, respectively. The corresponding neighbour
      joining (N-J) trees based on Lynch's and Hedrick's genetic distances resulted in
      similar topologies. However, these trees were not in agreement with the N-J
      dendrogram obtained from mtDNA data previously reported by Clemente et al.
      (2000). The disagreement between mtDNA and rDNA phenograms along with the
      observed correlation between rDNA variability and geographical and climatic
      variables suggest some form of selection, besides genetic drift and migration, is
      involved in the pattern of rDNA variation.

PMID- 12502259
TI  - Two different genes encoding acetylcholinesterase existing in cotton aphid (Aphis
      gossypii).
AB  - Two acetylcholinesterase (AChE) genes, Ace1 and Ace2, have been cloned from
      cotton aphid, Aphis gossypii Glover, using the rapid amplification of cDNA ends
      (RACE) technique. To the best of our knowledge, this should be the first direct
      molecular evidence that multiple AChE genes exist in insects. The Ace1 gene was
      successfully amplified along its full length of 2371 bp. The open reading frame
      is 2031 bp long and encodes 676 amino acids (GenBank accession No. AF502082). The
      Ace2 gene was amplified as a mega-fragment of 2130 bp lacking part of 5'-end
      untranslated region (UTR). The open reading frame is 1992 bp long and ecodes a
      protein of 664 amino acids (GenBank accession No. AF502081). Both genes have the
      conserved amino acids and features shared by the AChE family, but share only 35%
      identity in amino acid sequence. The Ace1 gene is highly homologous to the AChE
      gene of Schizaphis graminum (AF321574) with 95% identity, and Ace2 to that of
      Myzus persicae (AF287291) with 92% identity. Phylogenetic analysis showed that
      the two cloned AChEs of A. gossypii are different in evolution. The phylogenetic
      tree generated by the PHYLIP program package inferred that AChE2 of A. gossypii
      is a more ancestral form of AChE. Homology modeling of structures using Torpedo
      californica (2ACE_) and Drosophila melanogaster (1Q09:A) native
      acetylcholinesterase structure as main template indicated that the two AChEs of
      Aphis gossypii might have different three-dimensional structures. Alternative
      splicing of Ace1 near the 5'-end resulting in two proteins differing by the
      presence or absence of a fragment of four amino acids is also reported.

PMID- 12502260
TI  - Chloroplast microsatellite polymorphisms in Vitis species.
AB  - The use of consensus chloroplast microsatellites primers for dicotyledonous
      chloroplast genomes revealed the existence of intra and interspecific length
      variation within the genus Vitis. Three chloroplast microsatellite loci were
      found to be polymorphic in samples of Vitis vinifera, Vitis berlandieri, Vitis
      riparia, and Vitis rupestris out of a total of 10 consensus primer pairs tested.
      These polymorphisms were always due to a variable number of mononucleotide
      residues within A and (or) T stretches in the amplified regions. Chloroplast
      microsatellite polymorphisms were used to demonstrate the maternal inheritance of
      chloroplast in V. vinifera and to characterise the chloroplast haplotypes present
      in wine grape cultivars of this species grown in Spain and Greece. The different
      distribution of haplotype frequencies in the two ends of the Mediterranean growth
      area suggests the existence of independent domestication events for grapevine.

PMID- 12502261
TI  - Rapid classification of partial waxy wheats using PCR-based markers.
AB  - Mutations in the three homeologous waxy loci Wx-A1, Wx-B1, and Wx-D1 of a waxy
      wheat line have previously been characterized at the molecular level. Using
      combinations of these mutations, six types of partial waxy wheat plus wild type
      and waxy wheat (types 1-8) can be produced. Here, we describe primer sets for all
      three loci that can be used under a single set of conditions, allowing 32 lines
      to be characterized as types 1-8 in a single PCR run using a 96-well plate. Using
      multiplex PCR, mutations at the Wx-B1 and Wx-D1 loci can be identified in a
      single PCR, reducing the number of reactions necessary to identify and select the
      desired partial waxy wheat line. A single multiplex PCR can be used to detect all
      three mutations when products are analyzed using capillary electrophoresis on a
      microchip device. The PCR conditions and primers are effective with a number of
      cultivars from other countries, indicating that the mutations found at the Wx-A1
      and Wx-B1 loci of these cultivars likely have the same origins as the mutations
      in the corresponding loci of the waxy wheat line used in this study. The PCR
      selection method described here is an easy and effective alternative to the
      commonly used SDS-PAGE methods for identification of null alleles.

PMID- 12502262
TI  - Molecular phylogeny of the genus Hordeum using three chloroplast DNA sequences.
AB  - The genus Hordeum consists of three cytotypes (2x, 4x, and 6x). Its reproductive
      isolation has been incomplete between closely related species and hence the
      genetic relationship is reticulate and complex. We used 32 taxa of Hordeum and
      three chloroplast DNA sequences, matK, atpB-rbcL, and trnL-trnF in the current
      study. Molecular phylogenetic analysis based on sequence data of the three
      chloroplast DNA regions clearly demonstrated genetic relationships among taxa and
      origin of polypoids. The formation of H. secalinum likely involved hybridization
      between Hordeum marinum subsp. marinum and a Eurasian diploid possessing the H
      genome. The formation of hexaploid Hordeum brachyantherum involved hybridization
      between tetraploid H. brachyantherum and diploid H. marinum subsp. gussoneanum.
      The formation of three tetraploids, H. brachyantherum, Hordeum jubatum, and
      Hordeum guatemalense, probably involved hybridization between H. brachyantherum
      subsp. californicum and an altered H genome diploid. The formation of Hordeum
      arizonicum involved the two taxa Hordeum pusillum and H. jubatum.

PMID- 12502263
TI  - Polytene chromosome maps of the melon fly Bactrocera cucurbitae (Diptera:
      Tephritidae).
AB  - Standard photographic maps of the polytene chromosomes are presented for the
      melon fly Bactrocera cucurbitae, a serious pest of fleshy fruits and vegetables.
      Five larval salivary gland polytene chromosomes (10 polytene arms) were isolated,
      and their characteristic features and landmarks have been recognized. Banding
      patterns of each of the polytene arms are presented, where variation in band
      intensity and puffs appear to reflect fundamental differences in chromosomes. The
      whole polytene genome has been typically mapped by dividing it into 100 sections
      and the subsections were lettered. The mitotic chromosomes of larval brain
      ganglia are also examined, five pairs of autosomes and an XX/XY sex chromosome
      pair. In addition, a heterochromatic mass corresponding to the sex chromosomes
      are observed in the polytene nuclei of salivary gland tissue. This investigation
      showed that B. cucurbitae has excellent cytological material for polytene
      chromosome analysis and proved to be very useful for obtaining more detailed
      genetic information on the pest's natural populations.

PMID- 12502264
TI  - Genetic diversity in bambara groundnut (Vigna subterranea (L.) Verdc) landraces
      revealed by AFLP markers.
AB  - Bambara groundnut (Vigna subterranea (L.) Verdc), an African indigenous legume,
      is popular in most parts of Africa. The present study was undertaken to establish
      genetic relationships among 16 cultivated bambara groundnut landraces using
      fluorescence-based amplified fragment length polymorphism (AFLP) markers. Seven
      selective primer combinations generated 504 amplification products, ranging from
      50 to 400 bp. Several landrace-specific products were identified that could be
      effectively used to produce landrace-specific markers for identification
      purposes. On average, each primer combination generated 72 amplified products
      that were detectable by an ABI Prism 310 DNA sequencer. The polymorphisms
      obtained ranged from 68.0 to 98.0%, with an average of 84.0%. The primer pairs M
      ACA + P-GCC and M-ACA + P-GGA produced more polymorphic fragments than any other
      primer pairs and were better at differentiating landraces. The dendrogram
      generated by the UPGMA (unweighted pair-group method with arithmetic averaging)
      grouped 16 landraces into 3 clusters, mainly according to their place of
      collection or geographic origin. DipC1995 and Malawi5 were the most genetically
      related landraces. AFLP analysis provided sufficient polymorphism to determine
      the amount of genetic diversity and to establish genetic relationships in bambara
      groundnut landraces. The results will help in the formulation of marker-assisted
      breeding in bambara groundnut.

PMID- 12502265
TI  - Length and sequence heterogeneity in 5S rDNA of Populus deltoides.
AB  - The 5S rRNA genes and their associated non-transcribed spacer (NTS) regions are
      present as repeat units arranged in tandem arrays in plant genomes. Length
      heterogeneity in 5S rDNA repeats was previously identified in Populus deltoides
      and was also observed in the present study. Primers were designed to amplify the
      5S rDNA NTS variants from the P. deltoides genome. The PCR-amplified products
      from the two accessions of P. deltoides (G3 and G48) suggested the presence of
      length heterogeneity of 5S rDNA units within and among accessions, and the size
      of the spacers ranged from 385 to 434 bp. Sequence analysis of the non
      transcribed spacer (NTS) revealed two distinct classes of 5S rDNA within both
      accessions: class 1, which contained GAA trinucleotide microsatellite repeats,
      and class 2, which lacked the repeats. The class 1 spacer shows length variation
      owing to the microsatellite, with two clones exhibiting 10 GAA repeat units and
      one clone exhibiting 16 such repeat units. However, distance analysis shows that
      class 1 spacer sequences are highly similar inter se, yielding nucleotide
      diversity (pi) estimates that are less than 0.15% of those obtained for class 2
      spacers (pi = 0.0183 vs. 0.1433, respectively). The presence of microsatellite in
      the NTS region leading to variation in spacer length is reported and discussed
      for the first time in P. deltoides.

PMID- 12502266
TI  - Mapping quantitative trait loci in inbred backcross lines of Lycopersicon
      pimpinellifolium (LA1589).
AB  - Although tomato has been the subject of extensive quantitative trait loci (QTLs)
      mapping experiments, most of this work has been conducted on transient
      populations (e.g., F2 or backcross) and few homozygous, permanent mapping
      populations are available. To help remedy this situation, we have developed a set
      of inbred backcross lines (IBLs) from the interspecific cross between
      Lycopersicon esculentum cv. E6203 and L. pimpinellifolium (LA1589). A total of
      170 BC2F1 plants were selfed for five generations to create a set of homozygous
      BC2F6 lines by single-seed descent. These lines were then genotyped for 127
      marker loci covering the entire tomato genome. These IBLs were evaluated for 22
      quantitative traits. In all, 71 significant QTLs were identified, 15% (11/71) of
      which mapped to the same chromosomal positions as QTLs identified in earlier
      studies using the same cross. For 48% (34/71) of the detected QTLs, the wild
      allele was associated with improved agronomic performance. A number of new QTLs
      were identified including several of significant agronomic importance for tomato
      production: fruit shape, firmness, fruit color, scar size, seed and flower
      number, leaf curliness, plant growth, fertility, and flowering time. To improve
      the utility of the IBL population, a subset of 100 lines giving the most uniform
      genome coverage and map resolution was selected using a randomized greedy
      algorithm as implemented in the software package MapPop
      (http://www.bio.unc.edu/faculty/vision/lab/ mappop/). The map, phenotypic data,
      and seeds for the IBL population are publicly available
      (http://soldb.cit.cornell.edu) and will provide tomato geneticists and breeders
      with a genetic resource for mapping, gene discovery, and breeding.

PMID- 12502267
TI  - Development of an AFLP-based linkage map and localization of QTLs for seed fatty
      acid content in condiment mustard (Brassica juncea).
AB  - A genetic linkage map of Brassica juncea based on AFLP and RAPD markers was
      constructed using 131 F1-derived doubled-haploid (DH) plants from a cross between
      two mustard lines. The map included 273 markers (264 AFLP, 9 RAPD) arranged on 18
      linkage groups, and covered a total genetic distance of 1641 cM; 18.3% of the
      AFLP markers showed a segregation distortion (P < 0.01). The markers with biased
      segregation were clustered on seven linkage groups. QTLs for oil contents,
      palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), linoleic acid
      (18:2), linolenic acid (18:3), eicosenoic acid (20:1), and erucic acid (22:1),
      were mapped on the AFLP linkage map. Correlation studies among fatty acids in the
      DH population and the localization of QTLs involved in their control indicated
      that a major gene located on linkage group (LG) 2 controlled the elongation step
      of erucic acid.

PMID- 12502268
TI  - Mosaic microecological differential stress causes adaptive microsatellite
      divergence in wild barley, Hordeum spontaneum, at Neve Yaar, Israel.
AB  - Genetic diversity at 38 microsatellite (short sequence repeats (SSRs)) loci was
      studied in a sample of 54 plants representing a natural population of wild
      barley, Hordeum spontaneum, at the Neve Yaar microsite in Israel. Wild barley at
      the microsite was organized in a mosaic pattern over an area of 3180 m2 in the
      open Tabor oak forest, which was subdivided into four microniches: (i) sun-rock
      (11 genotypes), (ii) sun-soil (18 genotypes), (iii) shade-soil (11 genotypes),
      and (iv) shade-rock (14 genotypes). Fifty-four genotypes were tested for
      ecological-genetic microniche correlates. Analysis of 36 loci showed that allele
      distributions at SSR loci were nonrandom but structured by ecological stresses
      (climatic and edaphic). Sixteen (45.7%) of 35 polymorphic loci varied
      significantly (p < 0.05) in allele frequencies among the microniches. Significant
      genetic divergence and diversity were found among the four subpopulations. The
      soil and shade subpopulations showed higher genetic diversities at SSR loci than
      the rock and sun subpopulations, and the lowest genetic diversity was observed in
      the sun-rock subpopulation, in contrast with the previous allozyme and RAPD
      studies. On average, of 36 loci, 88.75% of the total genetic diversity exists
      within the four microniches, while 11.25% exists between the microniches. In a
      permutation test, G(ST) was lower for 4999 out of 5000 randomized data sets (p <
      0.001) when compared with real data (0.1125). The highest genetic distance was
      between shade-soil and sun-rock (D = 0.222). Our results suggest that
      diversifying natural selection may act upon some regulatory regions, resulting in
      adaptive SSR divergence. Fixation of some loci (GMS61, GMS1, and EBMAC824) at a
      specific microniche seems to suggest directional selection. The pattern of other
      SSR loci suggests the operation of balancing selection. SSRs may be either direct
      targets of selection or markers of selected haplotypes (selective sweep).

PMID- 12502269
TI  - Fluorescence in situ hybridization mapping of Avena sativa L. cv. SunII and its
      monosomic lines using cloned repetitive DNA sequences.
AB  - Fluorescent in situ hybridization (FISH) employing multiple probes was used with
      mitotic or meiotic chromosome spreads of Avena sativa L. cv. SunII and its
      monosomic lines to produce physical chromosome maps. The probes used were Avena
      strigosa pAs120a (which hybridizes exclusively to A-genome chromosomes), Avena
      murphyi pAm1 (which hybridizes exclusively to C-genome chromosomes), A. strigosa
      pAs121 (which hybridizes exclusively to A- and D-genome chromosomes), and the
      wheat rDNA probes pTa71 and pTa794. Simultaneous and sequential FISH employing
      two-by-two combinations of these probes allowed the unequivocal identification
      and genome assignation of all chromosomes. Ten pairs were found carrying
      intergenomic translocations: (i) between the A and C genomes (chromosome pair
      5A); (ii) between the C and D genomes (pairs 1C, 2C, 4C, 10C, and 16C); and (iii)
      between the D and C genomes (pairs 9D, 11D, 13D, and 14D). The existence of a
      reciprocal intergenomic translocation (10C-14D) is also proposed. Comparing these
      results with those of other hexaploids, three intergenomic translocations (10C,
      9D, and 14D) were found to be unique to A. sativa cv. SunII, supporting the view
      that 'SunII' is genetically distinct from other hexaploid Avena species and from
      cultivars of the A. sativa species. FISH mapping using meiotic and mitotic
      metaphases facilitated the genomic and chromosomal identification of the
      aneuploid chromosome in each monosomic line. Of the 18 analyzed, only 11 distinct
      monosomic lines were actually found, corresponding to 5 lines of the A genome, 2
      lines of the C genome, and 4 lines of the D genome. The presence or absence of
      the 10C-14D interchange was also monitored in these lines.

PMID- 12502270
TI  - Identification of wheat-barley translocations by sequential GISH and two-colour
      FISH in combination with the use of genetically mapped barley SSR markers.
AB  - Five wheat-barley translocations in a wheat background were characterized through
      the combination of cytogenetic and molecular genetic approaches. The wheat
      chromosome segments involved in the translocations were identified using
      sequential GISH and two-colour FISH with the probes pSc119.2 and pAs1. The barley
      chromatin in these lines was identified using SSR markers. A total of 45 markers
      distributed over the total barley genome were selected from a recently published
      linkage map of barley and tested on the translocation lines. The following
      translocations were identified: 2DS.2DL-1HS, 3HS.3BL, 6BS.6BL-4HL, 4D-5HS, and
      7DL.7DS-5HS. Wheat-barley disomic and ditelosomic addition lines for the
      chromosomes 3HS, 4H, 4HL, 5H, 5HL, and 6HS were used to determine the correct
      location of 21 markers and the position of the centromere. An intragenomic
      translocation breakpoint was detected on the short arm of the barley chromosome
      5H with the help of SSR marker analysis. Physical mapping of the SSR markers on
      chromosomes 1H and 5H was carried out using the intragenomic and the
      interspecific translocation breakpoints, as well as the centromere, as physical
      landmarks.

PMID- 12502271
TI  - Geographic structure of genetic variation in the widespread woodland grass Milium
      effusum L. A comparison between two regions with contrasting history and
      geomorphology.
AB  - Allozyme variation in the forest grass Milium effusum L. was studied in 21-23
      populations within each of two equally sized densely sampled areas in northern
      and southern Sweden. In addition, 25 populations from other parts of Eurasia were
      studied for comparison. The structure of variation was analysed with both
      diversity statistics and measures based on allelic richness at a standardised
      sample size. The species was found to be highly variable, but no clear geographic
      patterns in the distribution of alleles or in overall genetic differentiation
      were found, either within the two regions or within the whole sample. Thus, no
      inferences about the direction of postglacial migration could be made. Obviously,
      migration and gene flow must have taken place in a manner capable of randomising
      the distribution of alleles. However, there were clear differences in levels and
      structuring of the variation between the two regions. Levels of variation, both
      in terms of genetic diversity and allelic richness, were lower in northern Sweden
      as compared with southern Sweden. In contrast, different measures of geographic
      structure all showed higher levels of population differentiation in the northern
      region. This is interpreted as due to different geomorphological conditions in
      the two regions, creating a relatively continuous habitat and gene flow in the
      southern region as compared with the northern region where the species, although
      common, is confined to narrow and mutually isolated corridors in the landscape.

PMID- 12502272
TI  - An original mutation in soybean (Glycine max (L.) Merrill) involving degeneration
      of the generative cell and causing male sterility.
AB  - A spontaneous mutation causing male sterility has been detected in line BR97
      17739 from the soybean breeding program conducted by Embrapa-National Soybean
      Research Center. Meiotic division and male gametophyte development were analyzed
      in 10 male-sterile, female-fertile plants. Meiotic process had few irregularities
      related to chromosome segregation and affected about 2% of tetrads. Despite the
      high frequency of normal microspores, pollen sterility was total. After callose
      dissolution, microspores were released into the anther loculle and interphase
      nucleus was displaced from the center to one side of the cell. Displacement
      continued throughout normal microspore mitosis (PMI). After telophase, the
      hemispherical phragmoplast marked the place of cytokinesis. A typical generative
      cell, adjacent to the plasma membrane, and the vegetative one, containing most of
      the cytoplasm, were formed. In spite of the well-formed generative cell, pollen
      mitosis (PMII) failed to occur. The generative cell degenerated and was
      completely destroyed. The 3:1 segregation for male sterility in this line and its
      progenies indicate that a single recessive gene controls mutation.

PMID- 12502273
TI  - Predictor variables by developmental stages: a center for substance abuse
      prevention multisite study.
AB  - Five articles present the results obtained in a multisite study funded by the
      Center for Substance Abuse Prevention (CSAP). The overarching goal of this effort
      was to determine the efficacy of reducing severity of factors during childhood
      that are known to magnify the risk for substance abuse (SA) in adolescence. The
      factors targeted for preventive intervention were Behavior Self-Regulation,
      Parental Involvement, School Bonding, and Social Competence. Conceptualizing SA
      within a developmental framework, the findings indicate that prevention directed
      at youth between 3-14 years of age has a significant positive impact on
      attenuating intermediary factors predisposing to SA. In this introduction, both
      the theoretical framework and rationale guiding this cooperative agreement and
      the key findings are described.

PMID- 12502274
TI  - Prevention of substance abuse with rural head start children and families:
      results of project STAR.
AB  - The effectiveness of a comprehensive intervention with preschool children aimed
      at reducing the risk of later substance abuse was examined. The intervention
      targeted risk factors during the preschool years linked to later substance use in
      adolescence and adulthood. Head Start classrooms were randomly assigned to either
      the intervention or the control group. A classroom-based curriculum was delivered
      by Head Start teachers who received a number of training workshops and continued
      consultation. Parent training and home visits were also provided to intervention
      families. Positive parenting as well as parent-school involvement increased over
      the 1st year of intervention. Intervention families maintained the positive
      effects on parenting into the kindergarten year over a matched control group;
      however, effects on school bonding were not maintained. Improvements in social
      competence, reported by teachers and parents, were found at the end of
      kindergarten. No changes were found for self-regulation.

PMID- 12502275
TI  - The early risers longitudinal prevention trial: examination of 3-year outcomes in
      aggressive children with intent-to-treat and as-intended analyses.
AB  - The effects of participation following a 3-year preventive intervention trial
      targeting elementary school children with early-onset aggressive behavior were
      evaluated. Intent-to-treat analyses revealed that program participants, compared
      with controls, showed greater gains in social skills, academic achievement, and
      parent discipline, with mean scores in the normative range on the latter two
      constructs. As-intended participation in the Family Program, which included
      separate parent and child education and skills-training groups, was associated
      with improved parent discipline practices and gains in children's social skills,
      with level of child aggression moderating gains in academic achievement.
      Recommended level of FLEX family support contact time was associated with gains
      in academic achievement, concentration problems, and social skills, with parents
      of severely aggressive children showing greater reductions in parent distress.

PMID- 12502276
TI  - The Coping Power program at the middle-school transition: universal and indicated
      prevention effects.
AB  - This study evaluates the effects of an indicated preventive intervention and a
      universal preventive intervention. Children were identified as being at risk on
      the basis of 4th-grade teachers' ratings of children's aggressive and disruptive
      behaviors, and interventions were delivered during the 5th- and 6th-grade years.
      Children were randomly assigned to the Coping Power intervention, the universal
      intervention, the combined Coping Power plus universal intervention, or a control
      condition. The Coping Power program included child and parent components. Results
      indicated that all 3 intervention cells produced relatively lower rates of
      substance use at postintervention than did the control cell. The interventions
      also produced effects on 3 of the 4 predictor variable domains: children's social
      competence and self-regulation and parents' parenting skills.

PMID- 12502277
TI  - Predictors of participation in a family-focused preventive intervention for
      substance use.
AB  - This study reports patterns of involvement in a family-focused preventive
      intervention, Schools and Families Educating (SAFE) Children, targeting early
      predictors of risk for delinquency and drug use among 175 African American and
      Latino first-grade children living in economically disadvantaged inner-city
      neighborhoods. Three empirically derived patterns emerged: joiners, responders,
      and minimal responders. Joiners were immediately responsive and enthusiastic and
      participated fully. Responders attended fully only after extensive effort was
      made to recruit and retain them. However, once engaged, they attended fully and
      participated with enthusiasm. Minimal responders attended a few sessions
      sporadically even with extensive, ongoing effort to engage them. Ethnicity,
      marital status, parental antisocial behavior, economic and loss stressors,
      monitoring, and child's depression and hyperactivity were significant
      discriminators of group membership.

PMID- 12502278
TI  - Effectiveness of school-based family and children's skills training for substance
      abuse prevention among 6-8-year-old rural children.
AB  - This research tested the effectiveness of a multicomponent prevention program,
      Project SAFE (Strengthening America's Families and Environment), with 655 1st
      graders from 12 rural schools. This sample was randomly assigned to receive the I
      Can Problem Solve (ICPS) program (M. B. Shure & G. Spivack, 1979), alone or
      combined with the Strengthening Families (SF) program (K. L. Kumpfer, J. P.
      DeMarsh, & W. Child, 1989), or SF parent training only. Nine-month change scores
      revealed significantly larger improvements and effect sizes (0.35 to 1.26) on all
      outcome variables (school bonding, parenting skills, family relationships, social
      competency, and behavioral self-regulation) for the combined ICPS and SF program
      compared with ICPS-only or no-treatment controls. Adding parenting-only improved
      social competency and self-regulations more but negatively impacted family
      relationships, whereas adding SF improved family relationships, parenting, and
      school bonding more.

PMID- 12502279
TI  - A new class of acyclic nucleoside phosphonates: synthesis and biological activity
      of 9-[[(phosphonomethyl)aziridin-1-yl]methyl]guanine (PMAMG) and analogues.
AB  - A new class of acyclic nucleoside phosphonates PMAMG, PMAMA, PMAMC, and PMAMT
      (compounds 1, 2, 3 and 4) have been synthesized and tested in vitro against a
      wide variety of viruses, fungi and bacteria. PMAMG (1) was synthesized by the
      alkylation reaction of acetylguanine with the phosphonate side-chain, diisopropyl
      [[2-(bromomethyl)aziridin-1-yl]]methylphosphonate (9), followed by
      deesterification reaction in the presence of TMSBr. In similar way, PMAMA, PMAMC,
      and PMAMT were prepared.

PMID- 12502280
TI  - Daunomycin binding to deoxypolynucleotides with alternating sequences: complete
      thermodynamic profiles of heterogeneous binding sites.
AB  - Complete thermodynamic binding profiles for the interaction of the anticancer
      drug, daunomycin with natural DNA and synthetic deoxypolynucleotides were
      described. Fluorescence titration method was used to estimate the equilibrium
      binding constants. Binding isotherms were found to be surprisingly complex in
      some cases, presumably because there were heterogeneous sites even in simple
      deoxypolynucleotides of repeating sequence. Some polynucleotides consisting of
      alternating sequence contain at least two different binding sites for daunomycin.
      The binding affinity of the primary binding sites of alternating and non
      alternating sequences was found to differ by two orders of magnitude. An
      isothermal microtitration calorimeter was used to directly measure the binding
      enthalpy at 25 degrees C with a high sensitivity. The binding enthalpy of
      poly[d(A-T)] was found to be -5.5 Kcal/mol, which was much lower than any other
      polynucleotides, while the binding constant of the high affinity sites, was
      similar. In this report, the complete thermodynamic profiles of daunomycin
      binding to deoxypolynucleotides were reliably shown for the first time.

PMID- 12502281
TI  - Incorporation of 8-histaminyl-deoxyadenosine [8-(2-(4-imidazolyl)ethylamino)-2'
      deoxyriboadenosine] into oligodeoxyribonucleotides by solid phase phosphoramidite
      coupling.
AB  - The 3'phosphoramidite of 8-histaminyl deoxyadenosine has been prepared and
      successfully incorporated into a short oligodeoxyribonucleotide. The synthetic
      methodology leading to this preparation is given and the implications for
      developing new DNAzymes as well as probing unusual nucleic acid structures are
      discussed.

PMID- 12502282
TI  - Synthesis and biological evaluation of endocyclic 2',3'-didehydro-2',3'
      dideoxymethanocarba adenosine.
AB  - This is the first report describing the synthesis and conformation of
      methanocarba nucleosides incorporating an endo (beta-face) cyclopropyl at the
      2',3' position of 2',3'-didehydro-2',3'-dideoxy carbocyclic nucleosides. These
      nucleoside isosteres have been shown to exist in a unique extreme eastern
      conformation. This prediction was confirmed by x-ray crystallography and high
      resolution NMR spectroscopy. As expected, the methanocarba adenosine compound was
      neither a substrate nor an inhibitor of adenosine deaminase. However, some of the
      compounds synthesized demonstrated moderate antiviral activity against HSV-1. The
      methanocarba adenosine and its triphosphate form were evaluated as inhibitors of
      HIV-1 reverse transcriptase.

PMID- 12502283
TI  - Synthesis of 5-(pyridinyl and pyridiniumyl)-2'-deoxyuridine nucleosides:
      reversible electron traps for DNA.
AB  - The desire to produce reversible electron traps for direct, room temperature
      studies of excess electron transport in DNA duplexes and hairpins motivated our
      efforts first to link pyridines to 2'-deoxyuridine (pyridinyl-dU) and then to
      convert these new conjugates into pyridiniumyl-dU nucleosides. Base sensitivity
      studies presented here rule out general use of bipyridinediiumyl compounds, but
      show that pyridiniumyl compounds are suitable for use under the strand cleavage
      and base deprotection procedures required for automated solid-phase
      oligonucleotide synthesis. This paper presents the synthesis of four 5'-O-DMT
      protected 5-(N-methylpyridiniumyl)-dU conjugates using either ethynyl or
      ethylenyl linkers to join the pyridiniumyl and dU subunits.

PMID- 12502284
TI  - Inhibition of some hepatic glycosidases by the diseco nucleoside, 4-amino-3-(D
      glucopentitol-1-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analog.
AB  - The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-1-yl)-5-mercapto
      1,2,4-triazole and its 3-methyl analogue on alpha- and beta-glucosidases, beta
      glucuronidase as well as alpha-amylase have been investigated. alpha-Glucosidase
      is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent
      manner. The compounds showed a reversible inhibition of a competitive type for
      alpha-glucosidase. Moreover, they exert a relatively potent inhibition on alpha
      glucosidase with a Ki magnitude of 3.6 x 10(-4), 9.5 x 10(-5) M.

PMID- 12502285
TI  - Synthesis and anti-HCMV activity of novel acyclic nucleosides.
AB  - A series of novel acyclic nucleosides 10, 11, 21, and 22 were synthesized
      efficiently starting from D-lactose. The condensation of the mesylate 5 and 16
      with an adenine and cytosine base under standard nucleophilic substitution
      conditions (K2CO3, 18-Crown-6, DMF) afforded a series of acyclic novel
      nucleosides. Compound 21 displayed moderate anti-HCMV activity in the AD-169
      cells (EC50 = 18.5 microg/mL) without exhibiting any cytotoxicity up to 100
      microM.

PMID- 12502286
TI  - Reaction of N3-benzoyl-3',5'-O-(di-tert-butylsilanediyl)uridine with hindered
      electrophiles: intermolecular N3 to 2'-O protecting group transfer.
AB  - The compound N3-benzoyl-3',5'-O-(di-tert-butylsilanediyl)uridine 2 was alkylated
      with various alkyl iodides in CH3CN in the presence of base. Normal 2'-O
      alkylated products were obtained with methyl or benzyl iodide. If hindered alkyl
      iodides with beta-branching such as 2-ethylbutyl iodide were used as
      electrophiles under the same conditions, N3-alkyl-2'-O-benzoyl uridine
      derivatives were produced. This unexpected transformation is usually dormant with
      reactive alkylating agents, but expressed with sterically hindered, less reactive
      electrophiles. This unwanted reaction gives isomeric products whose spectra
      differ in only subtle ways from target compounds.

PMID- 12502287
TI  - Why evidence based oncology management.

PMID- 12502288
TI  - Bird's eye view of reimbursements. Kansas City oncology practice turns to the Web
      to improve processes for billing and collections.

PMID- 12502289
TI  - Manager's reports of variation in coding accuracy across U.S. oncology centers.
AB  - Advances in high-speed data processing capabilities, and the increasing reliance
      on information systems in comparative data assessment, are creating greater
      dependence on information systems, with a related need for more timely assessment
      of coding quality. Assessing the accuracy of coded and classified data becomes
      critical as the implementation of government compliance management requirements,
      along with the growing adoption of evidence-based medicine in error detection,
      serve to challenge healthcare researchers to consider the quality of coded data
      in management assessments. The implementation of larger, faster and more
      comprehensive databases in healthcare delivery settings is one response to this
      changing environment, but at a national level there will need to be some degree
      of uniformity in their utilization and management, if researchers are expected to
      rely on comparative benchmarks to fully assess organizational performance. In a
      nationwide survey of health information managers we found about 81 percent of
      respondents reported that significant coding errors existed in 5 percent or less
      of the records in their institutions. About 11 percent of respondents, however,
      reported that the coding errors existed in six to ten percent of their records.
      Regional and practice setting variation in reported coding error ranged widely,
      occurring across organizations as well as area locations. Related impact on
      comparative data-driven management assessment is discussed.

PMID- 12502290
TI  - One small step for man.

PMID- 12502291
TI  - When reimbursement issues go beyond reimbursement.

PMID- 12502292
TI  - Observations of reflectance distribution around sunglint from a coastal ocean
      platform.
AB  - A scanning spectral photometer is deployed on a rigid coastal ocean platform to
      measure upwelling solar radiances from the sea surface at nine elevation angles
      spanning 150 degrees of azimuth. Measured radiance distributions at 500 nm
      wavelength have been compared with traditional model simulations employing the
      Cox and Munk distribution of wave slopes. The model captures the general features
      of the observed angular reflectance distributions, but: (a) the observed peak
      value of sunglint near the specular direction is larger than simulated, except
      for a very calm sea; the model-measurement differences increase with wind speed
      and are largest for low solar elevation; (b) the observed sunglint is wider than
      simulated. In contrast to some previous studies, our results do not show a clear
      dependence of the mean square sea-surface slope on stability (air-sea temperature
      difference).

PMID- 12502293
TI  - Diffractive optical elements based on Fourier optical techniques: a new class of
      optics for extreme ultraviolet and soft x-ray wavelengths.
AB  - A diffractive optical element, based on Fourier optics techniques, for use in
      extreme ultraviolet/soft x-ray experiments has been fabricated and demonstrated.
      This diffractive optical element, when illuminated by a uniform plane wave, will
      produce two symmetric off-axis first-order foci suitable for interferometric
      experiments. The efficiency of this optical element and its use in direct
      interferometric determination of optical constants are also discussed. Its use in
      direct interferometric determination of optical constants is also referenced. Its
      use opens a new era in the use of sophisticated optical techniques at short
      wavelengths.

PMID- 12502294
TI  - Local improvement of the signal-to-noise ratio for diffractive optical elements
      designed by unidirectional optimization methods.
AB  - We present a straightforward method to design multilevel phase-only diffractive
      optical elements with a locally improved signal-to-noise ratio in the
      reconstruction. The method is generally applicable to all unidirectional design
      schemes, such as direct search, simulated annealing, or genetic optimization. As
      the shape and the location of the desired low noise areas are supplied by a bit
      map file the method allows for the design of basically any two-dimensional low
      noise area. The improvement in the signal-to-noise ratio that may be achieved is
      considerable but also entails reduced diffraction efficiency. The suggested
      method is applied to different beam-splitter design examples. All examples are
      calculated with the scalar diffraction approximation in the far field.

PMID- 12502295
TI  - Time multiplexing superresolution based on interference grating projection.
AB  - In a previous work done by the authors, it was shown that the superresolution
      concept based on two moving gratings could be effected by a physical grating
      attached to the object and a virtual grating. This concept was shown to be very
      efficient and exhibited features that are helpful in removing some artifacts
      caused when coherent illumination is used. Furthermore, it simplifies the optical
      and mechanical modules of the super-resolving system by removing the need for
      mechanical movement of one grating. However, the system still required the need
      for moving the first (encoding) grating attached to the input. In this study the
      encoding grating is replaced by use of a projected grating. This approach
      simplifies the need for attaching the grating to the input object and thus new
      applications, such as remote sensing can be considered. The theoretical concept
      is demonstrated and experimental results are shown.

PMID- 12502296
TI  - Ultra-low-power all-optical switching device by use of ytterbium-doped fiber
      Bragg gratings.
AB  - A new, to our knowledge, scheme of all-optical switching is put forward by use of
      an all-fiber Mach-Zehnder interferometer incorporating ytterbium-doped fiber
      Bragg gratings. The device utilizes the characteristics of the sharp change of
      group velocity in transmission with the detuning parameter, delta = 2pi
      n(1/lambda - 1/lambdaB). The switching is achieved by changing the Bragg
      wavelength of the ytterbium-doped arm of the interferometer. A very small shift
      of the Bragg wavelength can lead to a pi phase shift between the two arms, so the
      power needed to realize complete switching is much lower than that of other
      schemes. In addition, the device can compensate the dispersion of an optical
      pulse through the positive group velocity dispersion in transmission provided by
      the gratings.

PMID- 12502297
TI  - Signal evaluation for high-speed confocal measurements.
AB  - The confocal-detection principle is open especially for use in medical
      applications. For inspection systems applications for technical objects in
      reflection confocal setups are of growing importance. For such applications the
      confocal measurements need to have a very short measuring time. A fast detection
      system is needed and to satisfy this requirement only a small number of height
      levels are measured and a fast-evaluation algorithm is used. Drawbacks of the
      reduction of height levels are a greater influence of noise and additional
      systematic errors on the measured heights. Study the effects of the reduction are
      calculated, different evaluation algorithms are analyzed, and the optimization of
      the parameters is discussed.

PMID- 12502298
TI  - Adaptive binary joint transform correlator for image recognition.
AB  - Our research has shown that the autocorrelation peaks of a binary joint transform
      correlator are affected by input scenes' backgrounds. An adaptive method is
      proposed to overcome this problem. The image of interest is first extracted from
      the background based on the position of the highest correlation peak of the input
      and reference images. The extracted image is then correlated with the reference
      to obtain the final correlation peak. Numerical simulations showed that the final
      autocorrelation peak is the maximum constant for a specified reference image.

PMID- 12502299
TI  - Proposed algorithm for phase unwrapping.
AB  - A new, to our knowledge, two-dimensional phase-unwrapping algorithm is proposed.
      The algorithm, which is based on the global continuity of physical information
      (e.g. the three-dimensional surface profile of an object) being measured, uses
      the principle of least-phase difference to rectify errors caused by an erroneous
      2pi-phase jump in the initial unwrapped phase map obtained by the conventional
      phase-unwrapping method. Experimental results show that the proposed algorithm
      works well on a phase map that contains error sources, such as noises, phase
      discontinuity of more than pi, and insufficient sampling. Moreover, the algorithm
      is most suitable for unwrapping a phase map generated during shape measurement
      with a step-change surface on the test object, which is usually a critical
      problem in shape measurement.

PMID- 12502300
TI  - Near-infrared finger vein patterns for personal identification.
AB  - We have demonstrated a personal identification system that is based on near
      infrared finger vein patterns. Finger vein patterns of 678 volunteers are
      acquired by transmitting near-infrared light through a finger and capturing the
      image with a CCD camera. These vein patterns are enhanced by a background
      reduction filter. The similarity between two patterns is then quantified by use
      of the normalized maximum of the cross correlation of the two images after
      correction of the tilt angle. The enhanced finger vein pattern enabled 678
      persons to be successfully identified.

PMID- 12502301
TI  - Fast two-dimensional phase-unwrapping algorithm based on sorting by reliability
      following a noncontinuous path.
AB  - We describe what is to our knowledge a novel technique for phase unwrapping.
      Several algorithms based on unwrapping the most-reliable pixels first have been
      proposed. These were restricted to continuous paths and were subject to
      difficulties in defining a starting pixel. The technique described here uses a
      different type of reliability function and does not follow a continuous path to
      perform the unwrapping operation. The technique is explained in detail and
      illustrated with a number of examples.

PMID- 12502302
TI  - Robust, fast, and effective two-dimensional automatic phase unwrapping algorithm
      based on image decomposition.
AB  - We describe what is to our knowledge a novel approach to phase unwrapping. Using
      the principle of unwrapping following areas with similar phase values (homogenous
      areas), the algorithm reacts satisfactorily to random noise and breaks in the
      wrap distributions. Execution times for a 512 x 512 pixel phase distribution are
      in the order of a half second on a desktop computer. The precise value depends
      upon the particular image under analysis. Two inherent parameters allow tuning of
      the algorithm to images of different quality and nature.

PMID- 12502303
TI  - Class-associative multiple target detection by use of fringe-adjusted joint
      transform correlation.
AB  - We propose a class-associative correlation filter based technique for detecting a
      class of objects consisting of dissimilar patterns. The fringe-adjusted joint
      transform correlation algorithm is utilized to enhance the correlation
      performance, thus ensuring a strong and equal correlation peak for each element
      of the selected class. For enhanced performance, an enhanced version of the
      fringe-adjusted filter is incorporated in the class-associative multiple target
      detection process. The feasibility of the proposed technique has been tested by
      computer simulation.

PMID- 12502304
TI  - Image preprocessing for improving computational efficiency in implementation of
      restoration and superresolution algorithms.
AB  - Computational complexity is a major impediment to the real-time implementation of
      image restoration and superresolution algorithms in many applications. Although
      powerful restoration algorithms have been developed within the past few years
      utilizing sophisticated mathematical machinery (based on statistical optimization
      and convex set theory), these algorithms are typically iterative in nature and
      require a sufficient number of iterations to be executed to achieve the desired
      resolution improvement that may be needed to meaningfully perform postprocessing
      image exploitation tasks in practice. Additionally, recent technological
      breakthroughs have facilitated novel sensor designs (focal plane arrays, for
      instance) that make it possible to capture megapixel imagery data at video frame
      rates. A major challenge in the processing of these large-format images is to
      complete the execution of the image processing steps within the frame capture
      times and to keep up with the output rate of the sensor so that all data captured
      by the sensor can be efficiently utilized. Consequently, development of novel
      methods that facilitate real-time implementation of image restoration and
      superresolution algorithms is of significant practical interest and is the
      primary focus of this study. The key to designing computationally efficient
      processing schemes lies in strategically introducing appropriate preprocessing
      steps together with the superresolution iterations to tailor optimized overall
      processing sequences for imagery data of specific formats. For substantiating
      this assertion, three distinct methods for tailoring a preprocessing filter and
      integrating it with the superresolution processing steps are outlined. These
      methods consist of a region-of-interest extraction scheme, a background-detail
      separation procedure, and a scene-derived information extraction step for
      implementing a set-theoretic restoration of the image that is less demanding in
      computation compared with the superresolution iterations. A quantitative
      evaluation of the performance of these algorithms for restoring and
      superresolving various imagery data captured by diffraction-limited sensing
      operations are also presented.

PMID- 12502305
TI  - Holographically recorded photopolymer diffractive optical element for holographic
      and electronic speckle-pattern interferometry.
AB  - A diffractive optical element is described that can be used to implement a very
      simple self-aligning electronic speckle-pattern interferometer and holographic
      interferometer that requires only a laser source and a camera in the optical
      setup.

PMID- 12502306
TI  - Experimental validation of hybrid micro-macro optical method for distortion
      removal in multi-chip global free-space optical-interconnection systems.
AB  - Experimental validation of a distortion removal technique for multi-chip free
      space optical shuffle interconnections is presented. The free-space fabric links
      dense two-dimensional arrays of vertical cavity surface emitting laser(s)
      (VCSEL)(s) and detectors and must achieve full field registration on the order of
      10 microns across the entire array. The new hybrid micro-macro optical concept
      realizes the required high-registration accuracy by simultaneously eliminating
      distortion in each of the interleaved off-axis imaging systems that comprise the
      complete fabric. This is achieved by exploiting the typically low numerical
      aperture of VCSELs. Individually tailored beam-deflecting micro-optical elements
      were used to create symmetry about a central aperture for VCSEL beams in the
      optical system. Experiments were developed to quantify the registration accuracy,
      the VCSEL images, and the associated spot sizes. The experimental results show
      that beam steering can be implemented to remove distortion in off-axis free-space
      optical-interconnection systems.

PMID- 12502307
TI  - Isolation and structure elucidation of an isoflavone and a sesterterpenoic acid
      from Henriettella fascicularis.
AB  - A new isoflavone, 4',5,7-trihydroxy-6,8-dimethylisoflavone (1), and a new
      sesterterpenoic acid (2), together with five known compounds, lichexanthone (3),
      (-)-pinoresinol (4), betulinic acid, palmitic acid, and beta-sitosterol, were
      isolated from a dichloromethane extract of the branches of Henriettella
      fascicularis. Their structures were established by extensive spectroscopic
      methods. An attempt to determine the absolute stereochemistry of (2E,6S)-6
      [(1R,5Z,3aS,9R,10Z,12aR)-1,2,3,3a,4,7,8,9,12,12a-decahydro-9-hydroxy-3a,6,10
      trimethylcyclopentanocycloundecen-1-yl]-2-methylhept-2-enoic acid (2) was
      performed by single-crystal X-ray analysis, using Cu Kalpha radiation. Compound 1
      showed significant competitive binding to estrogen receptor beta and moderate
      antiestrogenic activity with cultured Ishikawa cells.

PMID- 12502308
TI  - Leishmanicidal and antiplasmodial activity of constituents of Smirnowia iranica.
AB  - Three unusual, highly oxygenated novel phenylpropanoids (1-3) and two novel
      isoflavans, 8-prenylmucronulatol (4) and smiranicin (6), were isolated from
      Smirnowia iranica together with a previously described isoflavan, glyasperin H
      (5). The structures were established using homo- and heteronuclear two
      dimensional NMR experiments. The isoflavans significantly inhibited the growth of
      extracellular stages of three Leishmania species in vitro, their activity against
      the intracellular stages being considerably lower. 8-Prenylmucronulatol (4)
      showed moderate in vitro toxicity against Plasmodium falciparum, without
      noticeable erythrocyte membrane effects at the inhibitory concentration. Because
      of the structural relationship of isoflavans with chalcones and aurones, some of
      which are potent antiprotozoal agents, the isoflavan skeleton may be a template
      structure in search for new compounds with leishmanicidal and antiplasmodial
      activity.

PMID- 12502309
TI  - Bacopaside III, bacopasaponin G, and bacopasides A, B, and C from Bacopa
      monniera.
AB  - Two new saponins, 3-O-[6-O-sulfonyl-beta-d-glucopyranosyl-(1-->3)]-alpha-l
      arabinopyranosyl pseudojujubogenin (1) and 3-O-[alpha-l-arabinofuranosyl-(1-->2)]
      alpha-l-arabinopyranosyl jujubogenin (2), a new matsutaka alcohol derivative,
      (3R)-1-octan-3-yl-(6-O-sulfonyl)-beta-d-glucopyranoside (3), a new phenylethanoid
      glycoside, 3,4-dihydroxyphenylethyl alcohol (2-O-feruloyl)-beta-d-glucopyranoside
      (4), and a new glycoside, phenylethyl alcohol [5-O-p-hydroxybenzoyl-beta-d
      apiofuranosyl-(1-->2)]-beta-d-glucopyranoside (5), were isolated from Bacopa
      monniera. Their structures were established by NMR, MS, and chemical methods.

PMID- 12502310
TI  - New dammarane and malabaricane triterpenes from Caloncoba echinata.
AB  - Three novel triterpenes, (11R,20R)-11,20-dihydroxy-24-dammaren-3-one (1),
      (17S,20R,24R)-17,25-dihydroxy-20,24-epoxy-14(18)-malabaricen-3-one (2), and
      (17R,20S,24R)-17,25-dihydroxy-20,24-epoxy-14(18)-malabaricen-3-one (3), were
      isolated from leaves of Caloncoba echinata. The structures were established using
      mainly 800 MHz NOESY and HMBC connectivities. The absolute stereochemistry of C
      11 in 1 and that of C-17 in 2 were established by the Mosher method. The
      stereochemistry of the side chains of the malabaricanes is compatible with their
      biosynthesis by a cascade opening of diepoxides. The isolated triterpenes
      inhibited growth of Plasmodium falciparum parasites in vitro apparently via
      incorporation into erythrocyte membrane, as suggested by transformation of
      erythrocytes into stomatocytes at a concentration level at which the growth
      inhibition was observed.

PMID- 12502311
TI  - Dictyoquinazols A, B, and C, new neuroprotective compounds from the mushroom
      Dictyophora indusiata.
AB  - In an effort to identify neuroprotective compounds against excitatory neurotoxins
      from edible and medicinal mushrooms, dictyoquinazols A (1), B (2), and C (3) have
      been isolated from the methanolic extract of the mushroom Dictyophora indusiata.
      On the basis of NMR studies, their structures have been assigned as unique
      quinazoline compounds, which are very rare in nature. 2 and 3 existed as mixtures
      of rotamers (2a, 2b and 3a, 3b) inseparable by HPLC because of fast
      interconversion. The E/Z isomers of these compounds were assigned by comparison
      of (1)H NMR, (13)C NMR, and NOESY spectra and by (3)J(C,H) coupling constants.
      Dictyoquinazols protected primary cultured mouse cortical neurons from glutamate-
      and NMDA-induced excitotoxicities in a dose-dependent manner.

PMID- 12502312
TI  - An extract of Tagetes lucida and its phenolic constituents as antioxidants.
AB  - Analysis of a methanolic extract of Tagetes lucida leaves has resulted in the
      isolation of a new flavonol glycoside, quercetagenin 3,4'-dimethyl ether 7-O-beta
      D-glucopyranoside (1), two new phenolic acids, 3-(2-O-beta-D-glucopyranosyl-4
      methoxyphenyl)propanoic acid (2) and its methylester (3), and known flavonols,
      aromatic acids, and 7-methoxycoumarin. Using the DPPH degrees test, the extract
      and some of its constituents showed a significant free-radical-scavenging effect
      in comparison to alpha-tocopherol and standard flavonols.

PMID- 12502313
TI  - Chemical constituents of the aerial parts of Schnabelia tetradonta.
AB  - A phytochemical study on the ethanol extract of the aerial parts of Schnabelia
      tetradonta led to the isolation of five new compounds, 1-5, together with seven
      known compounds. The structures of the new compounds were elucidated on the basis
      of spectral data interpretation as 2alpha,3alpha,23,29-tetrahydroxyolean-12-en-28
      oic acid (1), 3-O-beta-d-glucuronopyranosyl-2beta,3beta,16beta-trihydroxy-28
      norolean-12-en-15-on-23-oic acid (2), 21-O-beta-d-glucopyranosyl-3beta,21alpha,30
      trihydroxyolean-13(18)-en-24-oic acid (3), 6-C-beta-l-arabinopyranosyl-8-C-alpha
      l-arabinopyranosylapigenin (4), and 4-acetylaminoethylphenyl 1-O-[6-O-(Z)-p
      methoxycinnamoyl-beta-d-glucopyranosyl(1-->2)]-[beta-d-glucopyranosyl(1-->3)]
      alpha-l-rhamnopyranoside (5), respectively.

PMID- 12502315
TI  - An efficient conversion of taxinine to taxinine NN-1, an anticancer agent and a
      modulator of multidrug-resistant tumor cells.
AB  - Taxinine NN-1 (1), which shows significant activities as a modulator of multidrug
      resistant cancer cells and as an anticancer agent in an in vitro assay based on a
      HCC panel, was synthesized in order to obtain sufficient material for a higher
      order bioassay from easily available taxinine (2). The synthesis was achieved via
      intermediate 8, which was derived from 2 by the stepwise protection of a 9,10
      dihydroxyl group as acetonide and a 2-hydroxyl group as a MOM protecting group.
      The temporary elimination of a cinnamoyl group at C-5 of 8 and successive
      reduction of a C-13 carbonyl group of the resulting 9 gave 10 and the undesired
      13-epimer 11. The latter was recycled to 9 by oxidation with MnO(2). Stepwise
      acetylation and cinnamoylation at C-13 and C-5 of 10 and successive deprotection
      of the acetonide protecting group at C-9,10 of the resulting 13 gave diol 14.
      Diacetylation of 14 and deprotection of the MOM protecting group at C-2 of the
      resulting 15 gave 1. The overall yield of 1 was 45% in 11 steps from 2.

PMID- 12502314
TI  - Araguspongines K and L, new bioactive bis-1-oxaquinolizidine N-oxide alkaloids
      from Red Sea specimens of Xestospongia exigua.
AB  - In addition to the previously reported (+)-araguspongine A, (+)-araguspongine C,
      (+)-araguspongine D, (-)-araguspongine E, and (+)-xestospongin B, two new N-oxide
      araguspongines, (+)-araguspongine K and (+)-araguspongine L, are described here.
      Their structures were established on the basis of spectral analyses including
      (1)H-(15)N HMBC. The promising in vitro antimalarial and antituberculosis
      activities of araguspongine C are reported.

PMID- 12502316
TI  - Isolation of labradorins 1 and 2 from Pseudomonas syringae pv. coronafaciens.
AB  - Investigation of Pseudomonas syringae pv. coronafaciens cancer cell growth
      inhibitory constituents led to the isolation of 2-isobutyl-5-(3-indolyl)oxazole
      (1) and 2-n-pentyl-5-(3-indolyl)oxazole (2f), designated labradorins 1 (1) and 2
      (2f), related to pimprinine (2a). The structures were deduced by spectroscopic
      techniques and X-ray crystal structure determinations. Labradorin 1 (1) afforded
      GI(50) microg/mL values of 9.8 and 6.2 against the human cancer cell lines NCI-H
      460 (lung-NSC) and BXPC-3 (pancreas-a).

PMID- 12502317
TI  - Purealidin S and purpuramine J, bromotyrosine alkaloids from the Fijian marine
      sponge Druinella sp.
AB  - Two bromotyrosine alkaloids, purealidin S (2) and purpuramine J (5), were
      isolated from the Fijian marine sponge Druinella sp. Eight known bromotyrosine
      compounds were also isolated. This is the first report of a bromotyrosine N-oxide
      containing alkaloid. These two compounds were found to have moderate cytotoxic
      activity. In addition, bioassay data for the eight known bromotyrosine
      metabolites are reported.

PMID- 12502318
TI  - Triterpene glycosides from the deep-water North-Pacific sea cucumber Synallactes
      nozawai Mitsukuri.
AB  - Five non-sulfated triterpene glycosides, synallactosides A(1) (1), A(2) (2), B(1)
      (3), B(2) (4), and C (5), have been isolated from the sea cucumber Synallactes
      nozawai. Their structures have been deduced by extensive analysis of NMR and mass
      spectra. The glycosides 2-5 are new glycosides. Glycosides 2-4 have carbohydrate
      chains without precedent in the glycosides from sea cucumbers. This is the first
      time glycosides are found in members of the family Synallactidae.

PMID- 12502319
TI  - Semisynthesis of new sarcophine derivatives with chemopreventive activity.
AB  - The natural cembranolide sarcophine (3) and its lactone ring-opened analogue (10)
      were oxidized using selenium dioxide under different reaction temperatures to
      prepare hydroxylated derivatives. Nine new compounds were obtained, six of them
      targeted hydroxylated derivatives. The determination of regio- and
      stereochemistry as well as the mechanistic considerations on the selectivity
      observed in these reactions are discussed on the basis of 2D NMR and molecular
      modeling. In preliminary in vitro tests on inhibition of EBV-EA activation,
      compounds 10 and 12-15 have shown higher activity than the known chemopreventive
      agent sarcophytol A.

PMID- 12502320
TI  - Five new steroidal saponins from Solanum chrysotrichum leaves and their
      antimycotic activity.
AB  - Using bioactivity-directed isolation procedures, five new spirostan saponins and
      two sterol glycosides have been isolated from Solanum chrysotrichum leaves. The
      structure of these compounds was established based upon spectroscopic
      measurements, especially 1D and 2D NMR data of their peracetate derivatives.
      These compounds showed antimycotic activity. The most active compound is 6alpha-O
      beta-d-xylopyranosyl-(1-->3)-beta-d-quinovopyranosyl-(25R)-5alpha-spirostan
      3beta,23alpha-ol (2) (MIC =12.5, 12.5, 100, and 200 microg/mL against
      Trichophyton mentagrophytes, T. rubrum, Aspergillis niger, and Candida albicans,
      respectively).

PMID- 12502321
TI  - Bitungolides A-F, new polyketides from the Indonesian sponge Theonella cf.
      swinhoei.
AB  - Six new polyketides, bitungolides A-F (1-6), have been isolated from the
      Indonesian sponge Theonella cf. swinhoei and their structures elucidated by
      spectroscopic data and X-ray diffraction analysis. The bitungolides are a new
      class of Theonella metabolites that inhibit dual-specificity phosphatase VHR.

PMID- 12502322
TI  - Lyngbyastatin 1 and Ibu-epilyngbyastatin 1: synthesis, stereochemistry, and NMR
      line broadening.
AB  - The synthesis of a lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture combined with
      NMR and molecular modeling studies proved that natural lyngbyastatin 1 was only
      one Ibu epimer rather than a mixture of both and that the configuration of this
      epimer in the Ibu unit was R. The substance isolated with lyngbyastatin 1 was Ibu
      epidolastatin 12. The extreme broadness in the proton NMR spectra of
      lyngbyastatin 1 and Ibu-epidolastatin 12 was exchange broadening due to rotation
      about the Ibu-Ala amide bond. It was a consequence of (1) a small energy
      difference between the cis and trans forms of this bond, (2) a substantial
      difference in conformation between these forms, and (3) a lowered barrier between
      them compared to most amide bonds (due to steric hindrance). The synthetic
      lyngbyastatin 1-Ibu-epilyngbyastatin 1 mixture had significant activities against
      cancer cells and in stimulating actin polymerization, but was less active than
      dolastatin 11 in all assays.

PMID- 12502323
TI  - Semisynthetic analogues of the microtubule-stabilizing agent discodermolide:
      preparation and biological activity.
AB  - A series of 12 semisynthetic discodermolide analogues, 2-13, have been prepared
      using natural (+)-discodermolide (1) and evaluated for in vitro cytotoxicity
      against cultured murine P-388 leukemia and A-549 human adenocarcinoma cells.
      These semisynthetic analogues showed a significant variation of cytotoxicity and
      confirmed the importance of the C-7 through C-19 molecular fragment for potency.
      Specifically, these analogues suggested the importance of the C-11 and C-17
      hydroxyl groups and the C-13 double bond for the potency of discodermolide. The
      preparation, structure elucidation, and biological activity of these new
      analogues are described.

PMID- 12502324
TI  - New scalarane class sesterterpenes from an Indonesian sponge, Phyllospongia sp.
AB  - A series of scalarane class sesterterpenes (1-8) have been isolated from an
      Indonesian sponge, Phyllospongia sp. Their structures were determined by
      spectroscopic analysis and confirmed by single-crystal X-ray diffraction on
      compound 1. The absolute stereochemistry of 1 was established by modified
      Mosher's method.

PMID- 12502325
TI  - Brosimacutins A-I, nine new flavonoids from Brosimum acutifolium.
AB  - Nine new flavonoids, brosimacutins A-I (1-9), and four known flavonoids were
      isolated from the bark of Brosimum acutifolium, a Brazilian folk medicine
      ("Murure"). Their structures were elucidated by spectroscopic methods, including
      2D NMR. Brosimacutins A-I possess differentially functionalized isoprene units at
      C-8.

PMID- 12502326
TI  - New taxane diterpenoids from the leaves and twigs of Taxus sumatrana.
AB  - Two new taxoids, taxumairol Q (1) and 13-O-acetyl wallifoliol (2), have been
      isolated from the leaves and twigs of Taxus sumatrana. Taxuspine F and
      wallifoliol (10) have been isolated for the first time from the yew T. sumatrana.
      Seventeen known taxoid diterpenoids have also been isolated. The new derivatives,
      9,13-diacetyltaxumairol W (3), 10,13-dibenzoyltaxacustin (4), 7,13
      diacetylwallifoliol (5), 7,13-dibenzoylwallifoliol (6), and 7,9
      dibenzoyltaxumairol P (7), have been prepared by acylation of a crude mixture of
      taxoids. All structures were established primarily on the basis of 1D and 2D NMR
      techniques, including DEPT, COSY, and HMBC experiments, as well as chemical
      correlation with known compounds. Wallifoliol (10) exhibited significant
      cytotoxicities against both Hepa 59 T/VGH (human liver carcinoma) and KB (human
      oral epidermoid carcinoma) tumor cells. Taxuspine F and compound 5 possessed
      moderate activity against Hepa cells only, while 3, 6, 7, and 10-deacetylbaccatin
      III showed only marginal activity against Hepa cells.

PMID- 12502327
TI  - New cadinene sesquiterpenoids from the Formosan soft coral Xenia puerto-galerae.
AB  - Six new cadinene sesquiterpenoids, xenitorins A-F (1-6), were isolated from the
      methylene chloride solubles of the Formosan soft coral Xenia puerto-galerae. The
      structures were elucidated by 1D and 2D NMR spectral analysis, and their
      cytotoxicity against selected cancer cells was measured in vitro.

PMID- 12502328
TI  - Antimicrobial activities of naphthazarins from Arnebia euchroma.
AB  - Bioassay-directed fractionation of extract of Arnebia euchroma led to the
      isolation of alkannin (1), shikonin (2), and their derivatives (3-8) as the
      active principles against methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant enterococci (VRE). The stereochemistry of alpha
      methylbutyryl alkannin (8) is revealed for the first time, and the antimicrobial
      activity of 8 was compared with its corresponding diastereomer (9). The
      derivatives 3-9 showed stronger anti-MRSA activity [minimum inhibitory
      concentrations (MICs) ranged from 1.56 to 3.13 microg/mL] than alkannin or
      shikonin (MIC = 6.25 microg/mL). Anti-MRSA activity of derivatives was
      bactericidal with minimum bactericidal concentration (MBC)/MIC < or = 2. In a
      time-kill assay, the bactericidal activity against MRSA was achieved as rapidly
      as 2 h. The derivatives 3-9 were also active against vancomycin-resistant
      Enterococcus faecium (F935) and vancomycin-resistant Enterococcus faecalis (CKU
      17) with MICs similar to those with MRSA. Aromatic ester derivatives were also
      synthesized for antimicrobial activity comparison. None of these compounds were
      active against Gram-negative bacteria tested. Their cytotoxicity was also
      evaluated on selected cancer cell lines, and they expressed their activity in the
      range 0.6-5.4 microg/mL (CD(50)). Our results indicate that the ester derivatives
      of alkannin are potential candidates of anti-MRSA and anti-VRE agents with
      antitumor activity.

PMID- 12502329
TI  - Steroidal glycosides from the leaves of Cestrum nocturnum.
AB  - Further phytochemical analysis aimed at the steroidal glycoside constituents of
      the leaves of Cestrum nocturnum has resulted in the isolation of eight new
      steroidal glycosides (1-8), which were classified into a spirostanol saponin (1),
      a furostanol saponin (2), a pseudo-furostanol saponin (3), two pregnane
      glycosides (4, 5), two cholestane glycosides (6, 7), and pregnane-carboxylic acid
      gamma-lactone glycoside (8), and of two known spirostanol glycosides (9, 10). The
      structures of the new compounds were elucidated on the basis of chemical and
      spectroscopic evidence.

PMID- 12502330
TI  - Chemical constituents of the ascomycete Daldinia concentrica.
AB  - Four compounds, daldinone A (1), daldinone B (2), daldiniapyrone (4-methoxy-5
      carbomethoxy-6-pentyl-2H-pyran-2-one, 3), and daldinialanone (22R-hydroxylanosta
      7,9(11),24-trien-3-one, 4), were isolated from an ethyl acetate extract of fruit
      bodies of Daldinia concentrica collected in Europe. In addition, 11 known
      compounds, 4:5:4':5'-tetrahydroxy-1:1'-binaphthyl (5), 3,4,5-trihydroxy-1
      tetralone (6), (+)-orthosporin (7), curuilignan D (8), (22E)-cholesta
      4,6,8(14),22-tetraen-3-one (9), 3beta,22-dihydroxylanosta-7,9(11),24-triene (10),
      concentricol (11), concentricol B (12), concentricol C (13), concentricol D (14),
      and phenochalasin B (15), were obtained. The structures of the new compounds were
      elucidated by 2D NMR, MS, IR, and UV spectra and by X-ray crystallographic
      analysis. The absolute configurations of 1 and 4 were determined by CD
      spectroscopy and the modified Mosher's method, respectively. The chemotaxonomic
      relevance of the compounds obtained in this investigation is discussed.

PMID- 12502331
TI  - New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from
      Scilla sibirica.
AB  - Chromatographic separation of an extract of the bulbs of Scilla sibirica resulted
      in the isolation of five pyrrolidines, two pyrrolidine glycosides, six
      piperidines, one piperidine glycoside, and eight pyrrolizidines. 2,5-Dideoxy-2,5
      imino-glycero-d-manno-heptitol (homoDMDP, 1) is a common alkaloid in all plants
      of the Hyacinthaceae examined to date and was also found in S. sibirica. The
      structures of the new alkaloids were elucidated by spectroscopic methods as 7
      deoxy-homoDMDP (4), 2,5-dideoxy-2,5-imino-glycero-d-galacto-heptitol (5), the 4-O
      beta-d-mannoside (6) and the 4-O-beta-d-mannobioside (7) of 6-deoxy-homoDMDP (2),
      7-deoxyhomonojirimycin (12), 7-deoxyhomomannojirimycin (13), and
      polyhydroxypyrrolizidines, hyacinthacines A(4) (15), A(5) (16), A(6) (17), A(7)
      (18), B(4) (20), B(5) (21), and B(6) (22). HomoDMDP (1) is a potent inhibitor of
      beta-glucosidase and beta-galactosidase, while 6-deoxy-homoDMDP (2) showed
      significantly less inhibition. However, 7-deoxygenation of 1, leading to 4,
      showed no effect on the inhibitory activity toward both enzymes. Although 2 is
      not an inhibitor of alpha-l-fucosidase, the monomannoside of 2 shows inhibitory
      activity toward alpha-l-fucosidase. Elongation of the beta-mannopyranosyl chain
      of 6 to give 7 enhanced the inhibitory activity.

PMID- 12502332
TI  - New cytotoxic xenia diterpenoids from the Formosan soft coral Xenia umbellata.
AB  - Seven new cytotoxic xenicane-type diterpenoids, 9-deoxyxeniloide-E (1), 9-deoxy
      7,8-epoxyxeniloide-E (2), xeniolide-G (3), 9-deoxyxenialactol-C (4), xenibecin
      (5), xeniolide-H (6), and xenitacin (7), were isolated from the methylene
      chloride solubles of the Formosan soft coral Xenia umbellata. The structures were
      elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against
      selected cancer cells was measured in vitro.

PMID- 12502333
TI  - Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and
      related euphane triterpenes from the tree Melia dubia.
AB  - The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type
      triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth
      of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.6 microg/mL). Four of
      the others, the previously known methyl kulonate (8), kulinone (9), 16
      hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED(50)
      2.5-6.2 microg/mL) the P388 cancer cell line. In addition, two new euphane
      triterpenes were isolated and named dubione A (6) and dubione B (7). Structures
      for each of the 11 euphane triterpenes were established by spectral techniques
      that included HRMS and 2D NMR.

PMID- 12502334
TI  - Cytotoxic 3,20-epoxy-ent-kaurane diterpenoids from Isodon eriocalyx var.
      laxiflora.
AB  - Four new ent-kaurane diterpenoids, laxiflorins J-M (1-4), along with maoecrystal
      A (5) and maoecrystal P (6), were isolated from the leaves of Isodon eriocalyx
      var. laxiflora. Their structures were determined by spectroscopic analyses. All
      the compounds were assayed for their cytotoxic effects on human tumor K562, A549,
      and T24 cell lines. Compounds 1 and 6 showed significant inhibitory effects on
      human tumor K562 and T24 cells, with IC(50) values less than 0.5 microg/mL.
      Compound 3 also demonstrated cytotoxic activities against all three types of
      human tumor cells, with IC(50) values in the range of 1-25 microg/mL.

PMID- 12502335
TI  - Sesquiterpenes from Ferula penninervis.
AB  - The ethyl acetate soluble extract of the dried roots of Ferula penninervis gave
      17 new sesquiterpenes [15 of the guaiane-type, ferupennins A-O (1-15), and two of
      the eudesmane-type, 1alpha-hydroxy-2-oxo-5alpha,7beta,11betaH-eudesm-3-en
      6alpha,12-olide (16) and penninervin (17)] and nine known sesquiterpenes. The
      structures of the new compounds were elucidated on the basis of spectroscopic
      evidence and X-ray analysis. The absolute configuration of ferupennin A (1) was
      determined by a modified Mosher method.

PMID- 12502336
TI  - Scabrolides A-D, four new norditerpenoids isolated from the soft coral Sinularia
      scabra.
AB  - Four new norditerpenoids, scabrolides A-D (1-4), along with four known ones, 5-8,
      have been isolated from the dichloromethane extract of the Taiwanese soft coral
      Sinularia scabra. The structures of 1-4 were elucidated on the basis of extensive
      spectroscopic analyses, while the relative configurations were determined by the
      NOESY experiments. The epimeric metabolites 6 and 7 have been shown to exhibit
      strong cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.

PMID- 12502337
TI  - Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and
      SAR studies.
AB  - Fatty acid synthase (FAS) has been identified as a potential antifungal target.
      FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided
      fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia
      globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1
      13), including three new natural products (1, 4, 12), were isolated and their
      structures identified by spectroscopic interpretation. They represented five
      chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin
      related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4
      O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with
      IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56)
      analogues of the five chemotypes from our natural product repository and
      commercial sources were tested for their FAS inhibitory activity. Structure
      activity relationships for some chemotypes were investigated. All these compounds
      were further evaluated for antifungal activity against Candida albicans and
      Cryptococcus neoformans. Although there were several antifungal compounds in the
      set, correlation between the FAS inhibitory activity and antifungal activity
      could not be defined.

PMID- 12502338
TI  - An antiplasmodial lignan from Euterpe precatoria.
AB  - As a part of a study on new antiplasmodial natural products, a new 8-5' linked
      lignan dehydrodiconiferyl dibenzoate (2) and p-hydroxybenzoic acid (1) were
      isolated from the roots of the palm Euterpe precatoria. In contrast to compound
      1, compound 2 showed a moderate antiplasmodial activity.

PMID- 12502339
TI  - New steroidal glycosides from the fruits of Solanum anguivi.
AB  - Four new steroidal saponins, anguiviosides III (1), XI (2), XV (3), and XVI (4),
      were isolated and characterized from the fruits of Solanum anguivi. Their
      structures were elucidated on the basis of spectroscopic analysis. The occurrence
      of the cholestane glycosides 3 and 4 is considered from a biogenetic point of
      view.

PMID- 12502340
TI  - Potential antitumor-promoting diterpenes from the cones of Pinus luchuensis.
AB  - A new nor-labdane-type diterpene, 15-nor-labda-8(17),12E-dien-13,19-dienoic acid
      (1), along with five known diterpenes, 15-nor-14-oxolabda-8(17),12E-dien-19-oic
      acid (2), trans-communic acid (3), sandaracopimaric acid (4), dehydroabietic acid
      (5), and abieta-8,11,13-triene-15,18-diol (6), was isolated from the cones of
      Pinus luchuensis. The structure of 1 was established by chemical and
      spectroscopic methods. Among these isolates, compounds 2, 4, and 6 showed potent
      inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation
      induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.

PMID- 12502341
TI  - Absolute configuration of the antiinflammatory [correction of antiinflamatory]
      sponge natural product contignasterol.
AB  - Chiral auxiliary NMR analysis with C-22 (R/S)-MPA and (R/S)-MTPA esters has been
      used to demonstrate that the absolute configuration in the side chain of the
      antiinflammatory sponge metabolite contignasterol (1) is 22R, 24R.

PMID- 12502342
TI  - Three new guaianolides from Siyekucai (Ixeris chinenseis).
AB  - Three new guaianolides, 10alpha-hydroxy-3-oxoguaia-4(15),11(13)-dieno-12,6alpha
      lactone (1), 10alpha-hydroxy-3-oxo-4betaH-guaia-11(13)-eno-12,6alpha-lactone (2),
      and 10alpha-hydroxy-3-oxoguaia-4,11(13)-dieno-12,6alpha-lactone (3), named
      chinensiolides A, B, and C were isolated from the whole plant of Siyekucai
      (Ixeris chinensis). The structures were determined by HREIMS, UV, IR, and one-
      and two-dimensional NMR techniques ((1)H and (13)C NMR, COSY, HMQC, HMBC, and NOE
      difference and NOESY experiments). Compounds 1 and 2 were indicated to be a
      mixture of flexible conformers by analyses of their 1D NOE and NOESY spectra as
      well as the temperature dependence of their (1)H and (13)C NMR spectra.
      Chinensiolide B (2) was transformed to chinensiolide C (3) in a three-step
      conversion.

PMID- 12502343
TI  - DNA-damaging agents from Crypteronia paniculata.
AB  - A survey of crude plant extracts using a new yeast strain designed to identify
      DNA-damaging agents resulted in the identification of an extract prepared from
      Crypteronia paniculata. Bioassay-guided fractionation resulted in the isolation
      of three active compounds. Two of these were ellagic acid derivatives, namely,
      3,3'-di-O-methylellagic acid 4'-O-beta-d-xylopyranoside (1) and 3'-O-methyl-3,4
      methylenedioxyellagic acid 4'-O-beta-d-glucopyranoside (2). The third was
      identified as kaempferol-3-O-alpha-l-rhamnoside (3). The three principles
      exhibited strong, selective cytotoxity toward the RAD52 repair-deficient yeast
      strain.

PMID- 12502344
TI  - Two diphenylpropan-1,2-diol syringates from the roots of Erythrina variegata.
AB  - Two new diphenylpropan-1,2-diols, eryvarinols A (1) and B (2), were isolated from
      the roots of Erythrina variegata. Their structures were elucidated as 1-(4
      hydroxy-2-methoxyphenyl)-2-(4-hydroxy-3,5-dimethoxybenzoyloxy)-3-(4
      hydroxyphenyl)propan-1-ol (1) and its 3"-prenyl derivative (2) on the basis of
      spectroscopic and chemical evidence. Both these compounds are unusual
      diphenylpropan-1,2-diols with a syringyl group.

PMID- 12502345
TI  - Sodium 1-(12-hydroxy)octadecanyl sulfate, an MMP2 inhibitor, isolated from a
      tunicate of the family Polyclinidae.
AB  - Sodium 1-(12-hydroxy)octadecanyl sulfate (1) was isolated from a marine tunicate
      as a matrix metalloproteinase 2 (MMP2) inhibitor.(1) The structure was elucidated
      by a combination of spectroscopic and chemical methods. Compound 1 inhibited MMP2
      with an IC(50) value of 9.0 microg/mL.

PMID- 12502346
TI  - Structure and spasmolytic activity of eucalyptanoic acid from Eucalyptus
      camaldulensis var. obtusa and synthesis of its active derivative from oleanolic
      acid.
AB  - A new triterpenoid acid named eucalyptanoic acid (1) has been isolated from the
      fresh uncrushed leaves of Eucalyptus camaldulensis var. obtusa along with two
      known constituents, beta-sitosterol (2) and betulinic acid (3). The structure of
      1 has been established as 3beta-hydroxyolean-9(11),12-dien-28-oic acid through
      spectral studies including 1D and 2D NMR. 1 and its acetyl (1a) and acetylmethyl
      (1b) derivatives were tested for spasmolytic activity. 1b was found to be the
      most active spasmolytic, mediated through blockade of calcium influx at 1 mg/mL.
      In the present study 1b was also prepared starting from oleanolic acid (4).
      Acetylation of 4 gave 4a, which on methylation afforded 4b. Reaction of 4b with N
      bromosuccinimide (NBS) furnished 1b. Hence 4 may be regarded as the biogenetic
      precursor of 1. Compounds 4 and 4a were found inactive at 1 mg/mL, while 4b was
      moderately active in showing spasmolytic activity.

PMID- 12502347
TI  - Antiviral saponins from Tieghemella heckelii.
AB  - Arganine C (1) and a new saponin, tieghemelin (2), were isolated from Tieghemella
      heckelii fruits. Arganine C (1) strongly inhibited HIV entry into cells in a cell
      fusion assay. The less potent tieghemelin (2) was converted into arganine C (1)
      by reduction of its ethyl ester with sodium borohydride. The removal of the four
      sugar chains from arganine C (1) and tieghemelin (2) to give 16alpha
      hydroxyprotobassic acid 3-O-beta-D-glucopyranoside (3) and 16alpha
      hydroxyprotobassic acid 3-O-beta-D-glucuronopyranoside (4), respectively, caused
      total loss of activity in both cases. Arganine C (1) was not significantly
      cytotoxic to HeLa-CD4(+) cells at the level required to reduce the syncytium
      count to zero, suggesting it to be a promising candidate for further study as an
      antiviral drug.

PMID- 12502348
TI  - Lyngbyaloside B, a new glycoside macrolide from a Palauan marine cyanobacterium,
      Lyngbya sp.
AB  - A Palauan collection of the marine cyanobacterium Lyngbya sp., which had already
      afforded diverse peptide-based cytotoxins, also yielded a new glycoside macrolide
      exhibiting slight cytotoxicity. The compound was termed lyngbyaloside B (1) due
      to its structural analogy to the previously isolated lyngbyaloside (2).
      Lyngbyaloside B (1) appears to be only the third glycoside macrolide and second
      brominated compound of its kind from a marine cyanobacterium. Its gross structure
      was determined by a combination of NMR spectroscopy and mass spectrometric
      techniques. The relative stereochemistry for the 12 stereocenters is proposed on
      the basis of proton-proton spin-coupling constants and ROESY data.

PMID- 12502349
TI  - Iridoids from the rhizomes and roots of Valeriana jatamansi.
AB  - Five new iridoids, 1-homoacevaltrate (1), 1-homoisoacevaltrate (2), 11
      homohydroxyldihydrovaltrate (3), 10-acetoxy-1-homovaltrate hydrin (4), and 10
      acetoxy-1-acevaltrate hydrin (5), along with 10 known analogues, were isolated
      from the rhizomes and roots of Valeriana jatamansi. Structural elucidation was
      based on spectroscopic data interpretation.

PMID- 12502350
TI  - Biosynthesis of the lipophilic side chain in the cyclic hexadepsipeptide
      antibiotic IC101.
AB  - Antibiotic IC101 is a cyclic hexadepsipeptide having a C(15) lipophilic side
      chain. The side chain was shown to be synthesized in Streptomyces from acetate,
      propionate, and 3-methylbutyrate derived from leucine. Thus, the terminal
      isopentyl structure came from leucine and not from the mevalonate pathway.

PMID- 12502351
TI  - Plant-like biosynthetic pathways in bacteria: from benzoic acid to chalcone.
AB  - Although phenylpropanoids and flavonoids are common plant natural products, these
      major classes of biologically active secondary metabolites are largely absent
      from bacteria. The ubiquitous plant enzymes phenylalanine ammonia-lyase (PAL) and
      chalcone synthase (CHS) are key biosynthetic catalysts in phenylpropanoid and
      flavonoid assembly, respectively. Until recently, few bacterial counterparts were
      known, thus reflecting the dearth of these plant natural products in bacteria.
      This review highlights our progress on the biochemical and genetic
      characterization of recently identified streptomycete biosynthetic pathways to
      benzoic acid and type III polyketide synthase (PKS)-derived products. The
      sediment-derived bacterium "Streptomyces maritimus" produces benzoyl-CoA in a
      plant-like manner from phenylalanine involving a PAL-mediated reaction through
      cinnamic acid during the biosynthesis of the polyketide antibiotic enterocin. All
      but one of the genes encoding benzoyl-CoA biosynthesis in "S. maritimus" have
      been cloned, sequenced, and inactivated, providing a model for benzoate
      biosynthesis not only in this bacterium, but in plants where benzoic acid is an
      important constituent of many products. The recent discovery that bacteria harbor
      homodimeric PKSs belonging to the plant CHS superfamily of condensing enzymes has
      further linked the biosynthetic capabilities of plants and bacteria. A
      bioinformatics approach led to the prediction that the model actinomycete
      Streptomyces coelicolor A3(2) contains up to three type III PKSs. Biochemical
      analysis of one of the recombinant type III PKSs from S. coelicolor demonstrated
      activity as a 1,3,6,8-tetrahydroxynaphthalene synthase (THNS). A homology model
      of THNS based upon the known three-dimensional structure of CHS was constructed
      to explore the structural and mechanistic details of this new subclass of
      bacterial PKSs.

PMID- 12502352
TI  - Specific targeting of acetylcholinesterase and butyrylcholinesterase recognition
      sites. Rational design of novel, selective, and highly potent cholinesterase
      inhibitors.
AB  - Tacrine-based AChE and BuChE inhibitors were designed by investigating the
      topology of the active site gorge of the two enzymes. The homobivalent ligands
      characterized by a nitrogen-bridged atom at the tether level could be considered
      among the most potent and selective cholinesterase inhibitors described to date.
      The nitrogen-containing homobivalent ligands 3e,g and the sulfur-containing 3h
      validated the hypothesis of extra sites of interaction in the AChE and BuChE
      active site gorges.

PMID- 12502353
TI  - First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small
      molecule inhibitor achieved using rational design and homology modeling.
AB  - The first cocrystal structure of a bacterial FabH condensing enzyme and a small
      molecule inhibitor is reported. The inhibitor was obtained by rational
      modification of a high throughput screening lead with the aid of a S. pneumoniae
      FabH homology model. This homology model was used to design analogues that would
      have both high affinity for the enzyme and appropriate aqueous solubility to
      facilitate cocrystallization studies.

PMID- 12502354
TI  - Structure-activity relationship of (1-aryl-2-piperazinylethyl)piperazines:
      antagonists for the AGRP/melanocortin receptor binding.
AB  - Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin
      action.(1) In the hypothalamus, melanocortin peptide agonists act as satiety
      inducing factors that mediate their action through the melanocortin-4 receptor
      (MC4R) whereas AGRP is an opposing orexigenic agent. Novel inhibitors of the
      AGRP/MC4 binding based on (piperazinylethyl)piperazines were prepared, and their
      structure-activity relationship was established.

PMID- 12502355
TI  - Stereoselective synthesis of beta-lactams with polyaromatic imines: entry to new
      and novel anticancer agents.
AB  - We present herein stereoselective synthesis of novel beta-lactams using
      polyaromatic imines following the Staudinger reaction. Consistent mechanisms for
      these results have been advanced. As a measure of cytotoxicity, some of these
      compounds have been assayed against nine human cancer cell lines. Structure
      activity study has revealed that 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4
      aryl-2-azetidinones have potent anticancer activity. The presence of the acetoxy
      group at C(3) of the beta-lactams has proven to be obligatory for their
      anticancer activity.

PMID- 12502356
TI  - Desferrithiocin analogue based hexacoordinate iron(III) chelators.
AB  - Traditional thinking has been that hexacoordinate Fe(III) ligands are more
      effective at preventing iron's interactions with reactive oxygen species, most
      particularly the Fe(II)-mediated reduction of hydrogen peroxide to the hydroxyl
      radical (i.e., Fenton chemistry), than are ligands of lower denticity. Thus, a
      hexacoordinate derivative of the well-characterized tricoordinate ligand (S)-2
      (2,4-dihydroxyphenyl)-4,5-dihydro-4-thiazolecarboxylic acid [4'-(HO)-DADMDFT],
      (S,S)-1,11-bis[5-(4-carboxy-4,5-dihydrothiazol-2-yl)-2,4-dihydroxyphenyl]-4,8
      dioxaundecane, was designed with the aid of a molecular modeling program and
      synthesized. Evaluations both in vitro and in vivo were carried out to determine
      whether there is any advantage, at the level of prevention of Fenton chemistry,
      radical trapping, or iron clearance, to constructing a desferrithiocin-based
      hexacoordinate analogue. The hexacoordinate analogue was more effective at
      preventing the iron-mediated oxidation of ascorbate at low ligand/metal ratios
      than was its tricoordinate parent and can function as an excellent radical
      scavenger. At equivalent iron binding doses in the bile duct cannulated rodent,
      oral administration of the tricoordinate ligand was 3-fold more effective than
      was po administration of the hexacoordinate derivative. However, sc
      administration of the hexacoordinate derivative resulted in an efficiency that
      was 3 times greater than that of the tricoordinate chelator. Unfortunately, the
      rodent findings were not substantiated in the primates. The hexacoordinate ligand
      was only about one-half as efficient as its tricoordinate parent when
      administered sc. Owing to these results, po dosing was not attempted. Thus, there
      appears to be no overall advantage to coupling two molecules of 4'-(HO)-DADMDFT
      to afford a hexacoordinate derivative.

PMID- 12502357
TI  - Surface descriptors for protein-ligand affinity prediction.
AB  - Molecular descriptors calculated by the VolSurf program have been extensively
      used to model pharmacokinetic properties, e.g., passive permeability through the
      gastrointestinal tract or through the blood-brain barrier. These descriptors
      quantify steric, hydrophobic, and hydrogen bond interactions between model
      compounds and different environments. Since these interactions are the same as
      those involved in the ligand-receptor binding, VolSurf descriptors could
      potentially be relevant in modeling this process as well. We obtained a
      significant model (r(2) = 0.85, q(2) = 0.75) using VolSurf descriptors derived
      from the ligand, the protein, and the ligand-protein complex for a diverse set of
      38 structures previously used in the VALIDATE (ref 23) training set. Furthermore,
      a statistically significant model (r(2) = 0.94, q(2) = 0.89) was obtained using
      the same type of descriptors for a homogeneous set of glycogen phosphorylase
      inhibitors (ref 25). Using the VolSurf computational framework, both ligand
      receptor binding and the ligand's pharmacokinetic behavior can be modeled
      simultaneously during the preclinical aspects of drug discovery.

PMID- 12502358
TI  - The power of visual imagery in drug design. Isopavines as a new class of
      morphinomimetics and their human opioid receptor binding activity.
AB  - The importance of visual imagery and relational thinking manifests itself in a
      heuristic approach to the design and synthesis of potential morphinomimetics as
      agonists of the human mu receptor. The well-known class of alkaloids represented
      by the isopavine nucleus has a topological resemblance to the morphine skeleton,
      especially when viewed in a particular way. Enantiopure isopavines can be readily
      obtained from a 1,2 Stevens rearrangement of 13-substituted
      dihydromethanodibenzoazocines, prepared in four steps from d- and l-amino acids.
      Consideration of the topology and the expected orientation of the nitrogen lone
      pair for a better overlap with morphine necessitates the utilization of d-amino
      acids. By variation of the substituents on the aromatic rings and a judicious
      choice of ring substituents, it is possible to obtain low nanomolar binding to
      the human mu receptor while maintaining good to excellent mu/delta selectivity.
      Agonist-like activity is indicated in a functional assay for one of the analogues
      originally derived from d-alanine as a precursor. X-ray crystal structures of
      several compounds corroborate stereochemistries and overall topologies.

PMID- 12502359
TI  - Synthesis and structure-activity relationships of 6,7-disubstituted 4
      anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible
      inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor
      (EGFR) and the human epidermal growth factor receptor-2 (HER-2).
AB  - A series of of 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile derivatives
      that function as irreversible inhibitors of EGFR and HER-2 kinases have been
      prepared. These inhibitors have, at the 6-position, butynamide, crotonamide, and
      methacrylamide Michael acceptors bearing water-solublilizing substituents. These
      compounds were prepared by acylation of 6-amino-4-(arylamino)quinoline-3
      carbonitriles with unsaturated acid chlorides or mixed anhydrides. We performed
      competitive reactivity studies showing that attaching a dialkylamino group onto
      the end of the Michael acceptor results in compounds with greater reactivity due
      to intramolecular catalysis of the Michael addition. This, along with improved
      water-solubility results in compounds with enhanced biological properties. We
      present molecular modeling results consistent with the proposed mechanism of
      inhibition. One compound, 5 (EKB-569), which shows excellent oral in vivo
      activity, was selected for further studies and is currently in phase I clinical
      trials for the treatment of cancer.

PMID- 12502360
TI  - Hydantoin-substituted 4,6-dichloroindole-2-carboxylic acids as ligands with high
      affinity for the glycine binding site of the NMDA receptor.
AB  - A novel series of C-3 substituted 4,6-dichloroindole-2-carboxylic acids was
      synthesized to investigate the influence of different hydrogen-bond donor and
      acceptor groups at this specific position on the affinity to the glycine site of
      the NMDA receptor. These novel 3-indolylmethyl derivatives with ring-open
      (amines, sulfonamides, amides, ureas) and cyclic substituents (imidazolidin-2
      ones, (thio)hydantoins) led to the discovery that compounds bearing a hydantoin
      substituent at the C-3 position of the indole nucleus are the most promising
      ones. In this series the hydantoins, ureas, and imidazolidin-2-ones were
      identified as very potent inhibitors of the binding of the glycine site specific
      ligand [(3)H]MDL 105,519 to pig cortical brain membranes. Since the hydantoins
      can be produced via a versatile synthetic approach, further amendments of the
      hydantoin-substituted compounds were conducted to elucidate the influence of
      aromatic and aliphatic moieties at position 3 of the hydantoin as well as of
      sterically hindered compounds (5-substituted hydantoins). On the basis of the
      pharmacological data obtained in displacement experiments with [(3)H]MDL 105,519
      and the emerging structure-activity relationships, we confirm the existing
      pharmacophore model that suggests a hydrogen-bond acceptor and an aromatic
      substituent at position 3 of the indole as the key features for high affinity.
      Log P values indicate brain permeability and selected compounds showed
      anticonvulsant activity in vivo. Binding studies for the sodium channel (site 2)
      were also performed on some selected compounds.

PMID- 12502361
TI  - Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and
      computational rationalization of experimental ligand-binding specificities.
AB  - The ligand-binding characteristics of rat and human CYP2D isoforms, i.e., rat
      CYP2D1-4 and human CYP2D6, were investigated by measuring IC(50) values of 11
      known CYP2D6 ligands using 7-methoxy-4-(aminomethyl)coumarin (MAMC) as substrate.
      Like CYP2D6, all rat CYP2D isozymes catalyzed the O-demethylation of MAMC with
      K(m) and V(max) values ranging between 78 and 145 microM and 0.048 and 1.122 min(
      1), respectively. To rationalize observed differences in the experimentally
      determined IC(50) values, homology models of the CYP2D isoforms were constructed.
      A homology model of CYP2D6 was generated on the basis of crystallized rabbit
      CYP2C5 and was validated on its ability to reproduce binding orientations
      corresponding to metabolic profiles of the substrates and to remain stable during
      unrestrained molecular dynamics simulations at 300 K. Twenty-two active site
      residues, sharing up to 59% sequence identity, were identified in the CYP2D
      binding pockets and included CYP2D6 residues Phe120, Glu216, and Asp301.
      Electrostatic potential calculations displayed large differences in the negative
      charge of the CYP2D active sites, which was consistent with observed differences
      in absolute IC(50) values. MD studies on the binding mode of sparteine,
      quinidine, and quinine in CYP2D2 and CYP2D6 furthermore concurred well with
      experimentally determined IC(50) values and metabolic profiles. The current study
      thus provides new insights into differences in the active site topology of the
      investigated CYP2D isoforms.

PMID- 12502362
TI  - Unique structure-activity relationship for 4-isoxazolyl-1,4-dihydropyridines.
AB  - A series of 4-isoxazolyl-1,4-dihydropyridines (IDs) were prepared and
      characterized, and their interaction with the calcium channel was studied by
      patch clamp analysis. The structure-activity relationship (SAR) that emerges is
      distinct from the 4-aryldihydropyridines (DHPs), and affinity increases
      dramatically at higher holding potentials. Thus, among the 3'-arylisoxazolyl
      analogues p-Br > p-Cl >> p-F, and p-Cl > m-Cl > o-Cl >> o-MeO. Four of the
      analogues were examined by single-crystal X-ray diffractometry, and all were
      found to adopt an O-exo conformation in the solid state. The calculated barrier
      to rotation, however, suggests that rotation about the juncture between the
      heterocyclic rings is plausible under physiological conditions. A variable
      temperature NMR study confirmed the computation. With Striessnig's computational
      sequence homologation procedure, a working hypothesis was derived from the data
      that explains the unique SAR for IDs.

PMID- 12502363
TI  - Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3
      oxododecanoyl)-L-homoserine lactone as immune modulators.
AB  - Comparative immune modulatory activity for a range of synthetic analogues of a
      Pseudomonas aeruginosa signal molecule, N-(3-oxododecanoyl)-l-homoserine lactone
      (3O, C(12)-HSL), is described. Twenty-four single or combination systematic
      alterations of the structural components of 3O, C(12)-HSL were introduced as
      described. Given the already defined immunological profile of the parent
      compound, 3O, C(12)-HSL, these compounds were assayed for their ability to
      inhibit murine and human leucocyte proliferation and TNF-alpha secretion by
      lipopolysaccharide (LPS) stimulated human leucocytes in order to provide an
      initial structure-activity profile. From IC(50) values obtained with a murine
      splenocyte proliferation assay, it is apparent that acylated l-homoserine
      lactones with an 11-13 C side chain containing either a 3-oxo or a 3-hydroxy
      group are optimal structures for immune suppressive activity. These derivatives
      of 3O, C(12)-HSL with monounsaturation and/or a terminal nonpolar substituent on
      the side chain were also potent immune suppressive agents. However, structures
      lacking the homoserine lactone ring, structures lacking the l-configuration at
      the chiral center, and those with polar substituents were essentially devoid of
      activity. The ability of compounds selected from the optimal activity range to
      modulate mitogen-driven human peripheral blood mononuclear cell proliferation and
      LPS-induced TNF-alpha secretion indicates the suitability of these compounds for
      further investigation in relation to their molecular mechanisms of action in TNF
      alpha driven immunological diseases, particularly autoimmune diseases such as
      psoriasis, rheumatoid arthritis, and type 1 (autoimmune) diabetes.

PMID- 12502364
TI  - Relationship between stereochemistry and the beta3-adrenoceptor agonistic
      activity of 4'-hydroxynorephedrine derivative as an agent for treatment of
      frequent urination and urinary incontinence.
AB  - This report proposes a beta(3)-adrenoceptor (AR) selective agonist, 2-[2-chloro-4
      (2-([(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1
      methylethyl]amino)ethyl)phenoxy]acetic acid (1a), as a novel agent for treating
      urinary bladder dysfunction. This compound and its relatives have a unique
      feature among beta(3)-AR agonists: two chiral carbons are adjacently structured
      on the left side of the molecule. To study the relationship between the
      stereoconfiguration of the vicinal chiral carbons in 1a and beta-AR agonistic
      activity, the four stereoisomers were synthesized via oxazolidinone prepared by
      intracyclization involving inversion of the beta-hydroxy group. The in vitro
      assays using rat atria for beta(1)-AR, rat uteri for beta(2)-AR, and ferret
      detrusor for beta(3)-AR showed that 1a possessed potent beta(3)-AR agonistic
      activity (EC(50) = 3.85 nM) and 3700- and 1700-fold selectivity for beta(3)-AR
      relative to beta(1)- and beta(2)-AR, respectively. Comparison of the four isomers
      revealed that the (alphaS,betaR)-compound (1a) was not only the most potent
      agonist but was also the most selective for beta(3)-AR. In the anesthetized rat,
      intravenous administration of 1a brought about a sufficient decrement of the
      intrabladder pressure (ED(50) = 12 microg/kg), and intraduodenal administration
      of 2a, which is the ethyl ester of 1a, led to same result (ED(50) = 0.65 mg/kg).
      Moreover, no effects on the cardiovascular system were observed in either test.

PMID- 12502365
TI  - Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl
      moiety at the 6-position: a highly potent and orally bioavailable non-peptide
      antagonist for the human luteinizing hormone-releasing hormone receptor.
AB  - We have previously disclosed the first potent and orally effective non-peptide
      antagonist for the human luteinizing hormone-releasing hormone (LHRH) receptor, a
      thieno[2,3-b]pyridin-4-one derivative, T-98475 (1). Extensive research on
      developing non-peptide LHRH antagonists has been carried out by employing a
      strategy of replacing the thienopyridin-4-one nucleus with other heterocyclic
      surrogates. We describe herein the design and synthesis of a series of thieno[2,3
      d]pyrimidine-2,4-dione derivatives containing a biaryl moiety, which led to the
      discovery of a highly potent and orally active non-peptide LHRH antagonist, 5-(N
      benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-6-[4-(3-methoxyureido)phenyl]
      3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (9k: TAK-013). Compound 9k
      showed high binding affinity and potent in vitro antagonistic activity for the
      human receptor with half-maximal inhibition concentration (IC(50)) values of 0.1
      and 0.06 nM, respectively. Oral administration of 9k caused almost complete
      suppression of the plasma LH levels in castrated male cynomolgus monkeys at a 30
      mg/kg dose with sufficient duration of action (more than 24 h). The results
      demonstrated that the thienopyrimidine-2,4-dione core is an excellent surrogate
      for the thienopyridin-4-one and that thienopyrimidine-2,4-diones and
      thienopyridin-4-ones constitute a new class of potent and orally bioavailable
      LHRH receptor antagonists. Furthermore, molecular modeling studies indicate that
      the unique methoxyurea side chain of 9k preferentially forms an intramolecular
      hydrogen bond between the aniline NH and the methoxy oxygen atom. The hydrogen
      bond will shield the hydrogen bonding moieties from the solvent and reduce the
      desolvation energy cost. It is therefore speculated that the intramolecular
      hydrogen bond resulting from judicious incorporation of an oxygen atom into the
      terminal alkyl group of the urea may increase the apparent lipophilicity to allow
      increased membrane permeability and consequently to improve the oral absorption
      of 9k in monkeys. On the basis of its profile, compound 9k has been selected as a
      candidate for clinical trials and it is expected that it will provide a new class
      of potential therapeutic agents for the clinical treatment of a variety of sex
      hormone-dependent diseases.

PMID- 12502366
TI  - Biphenylsulfonamide endothelin receptor antagonists. 4. Discovery of N-[[2'
      [[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]- 2
      yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), a highly potent and orally
      active ET(A) selective antagonist.
AB  - We have previously disclosed the selective ET(A) receptor antagonist N-(3,4
      dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (1, BMS
      193884) as a clinical development candidate. Additional SAR studies at the 2'
      position of 1 led to the identification of several analogues with improved
      binding affinity as well as selectivity for the ET(A) receptor. Following the
      discovery that a 3-amino-isoxazole group displays significantly improved
      metabolic stability in comparison to its 5-regioisomer, the 3-amino-isoxazole
      group was combined with the optimal 2'-substituent leading to 16a (BMS-207940).
      Compound 16a is an extremely potent (ET(A) K(i) = 10 pM) and selective (80,000
      fold for ET(A) vs ET(B)) antagonist. It is also 150-fold more potent and >6-fold
      more selective than 1. The bioavailability of 16a was 100% in rats and the
      systemic clearance and volume of distribution are higher than that of 1. In rats,
      intravenous 16a blocks big ET pressor responses with 30-fold greater potency than
      1. After oral dosing at 3 micromol/kg, 16a displays enhanced duration relative to
      1.

PMID- 12502367
TI  - New benzo[h][1,6]naphthyridine and azepino[3,2-c]quinoline derivatives as
      selective antagonists of 5-HT4 receptors: binding profile and pharmacological
      characterization.
AB  - A series of benzo[h][1,6]naphthyridine and azepino[3,2-c]quinoline derivatives
      were prepared and evaluated to determine the necessary requirements for high
      affinity on the 5-HT(4) receptors and high selectivity versus other receptors.
      The compounds were synthesized by substituting the chlorine atom of
      benzonaphthyridines and azepinoquinolines with various N-alkyl-4
      piperidinylmethanolates. They were evaluated in binding assays with [(3)H]GR
      113808 as the 5-HT(4) receptor radioligand. The affinity values (K(i) or
      inhibition percentages) depended upon the substituent on the aromatic ring on one
      hand and the substituent on the lateral piperidine chain on the other hand. A
      chlorine atom produced a marked drop in activity while a N-propyl or N-butyl
      group gave compounds with nanomolar affinities (1 < K(i) < 10 nM). Among the most
      potent ligands (3a, 4a, 5a), 4a was selected on the basis of its high affinity
      and selectivity for pharmacological screening and was evaluated in vivo in
      specific tests. This compound reveals itself as an antagonist/low partial agonist
      in the COS-7 cells stably expressing the 5-HT(4(a)) receptor. Derivative 4a also
      showed in vivo potent analgesic activity in the writhing test at very low doses.

PMID- 12502368
TI  - Studies on the mechanisms of activation of indolequinone phosphoramidate
      prodrugs.
AB  - Previously a series of 2- and 3-substituted indolequinone phosphoramidate
      prodrugs was synthesized, and the compounds were shown to be nanomolar inhibitors
      of cell proliferation. The activation of these compounds following both one- and
      two-electron reduction has been investigated. (31)P NMR experiments demonstrated
      that both series of compounds undergo rapid activation following two-electron
      reduction. Additionally, the 3-series of compounds undergo rapid activation
      following one-electron reduction, while activation of the 2-series of compounds
      via this mechanism is very slow. The activation of these prodrugs by direct
      displacement using sulfur nucleophiles such as glutathione has been examined.
      Activation via this route is rapid for the 3-regioisomers, but is considerably
      slower for the 2-substituted analogues under similar conditions. Together these
      findings suggest that drug delivery via two-electron reduction from the 2
      position is the more selective prodrug strategy.

PMID- 12502369
TI  - 8-Aza-immucillins as transition-state analogue inhibitors of purine nucleoside
      phosphorylase and nucleoside hydrolases.
AB  - The 8-aza-immucillins (8-aza-9-deazapurines linked from C9 to C1 of 1,4-dideoxy
      1,4-iminoribitol) have been designed as transition-state analogues of the
      reactions catalyzed by purine nucleoside phosphorylase and nucleoside hydrolases.
      Syntheses of the 8-aza-immucillin analogues of inosine and adenosine are
      described. They are powerful inhibitors of the target enzymes with equilibrium
      dissociation constants as low as 42 pM.

PMID- 12502370
TI  - New N-n-propyl-substituted 3-aryl- and 3-cyclohexylpiperidines as partial
      agonists at the D4 dopamine receptor.
AB  - We have previously reported that compounds dimethyl-substituted on the phenyl
      ring of N-n-propyl-3-phenylpiperidines (PPEs) have a high (nM) affinity and
      selectivity toward the D(4) dopamine receptor (D(4) DAR) with m,p-dimethyl PPE
      (1) having the highest affinity and selectivity. In the present paper we have
      investigated the role of the methyl substitution by the synthesis of
      monomethylated (2a-c) and nonmethylated (2d) PPEs followed by the
      characterization of their biological properties using receptor binding assays.
      Our findings reveal that the methyl substitution of the phenyl ring is not
      necessary for a high and selective binding affinity to the D(4) DAR. Moreover, we
      have also synthesized cyclohexylpiperidines (CHPEs, 3a-d), which all showed
      higher binding affinities for the D(4) DAR than their aromatic counterparts.
      These results indicate that a pi-pi type interaction of the phenyl ring of PPEs
      with the D(4) DAR might not be essential, whereas a simple hydrophobic attraction
      between the cyclohexyl substituent of CHPEs and a hypothesized lipophilic pocket
      of the receptor might be crucial. Furthermore, functional assays indicate that
      3d, as well as 1, are partial agonist at the D(4) DAR and therefore might
      represent new pharmacological tools to investigate the role of D(4) DAR
      activation in the control of cognitive functions and emotional states in health
      and disease.

PMID- 12502371
TI  - Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia
      selective analogues of tirapazamine.
AB  - Tirapazamine (TPZ, 1,2,4-benzotriazin-3-amine 1,4-dioxide) is a bioreductive
      hypoxic cytotoxin currently in Phase II/III clinical trials in combination with
      radiotherapy and with cisplatin-based chemotherapy. As part of a program to
      develop TPZ analogues with improved solubility/potency and therapeutic indices,
      we synthesized 34 1,2,4-benzotriazin-3-amine 1,4-dioxides (BTO) to examine
      structure-activity relationships (SAR) for ring substitution. The electronic,
      hydrophobic, and steric parameters of substituents at the 5-, 6-, 7-, and 8
      positions were systematically varied, and the aqueous solubility and one-electron
      reduction potentials [E(1)] of the analogues were determined. For each compound,
      we determined cell killing of mouse SCCVII tumor cells in vitro under aerobic and
      hypoxic conditions by clonogenic survival and determined their relative hypoxic
      toxicity (RHT; relative to TPZ) and hypoxic cytotoxicity ratio (HCR). A subset of
      compounds was independently evaluated using a 96-well SRB proliferation assay,
      the data from which correlated well with that derived by the clonogenic endpoint.
      Most substituents, except 5- and 8-dimethylamino and 8-diethylamino, gave
      analogues less soluble than TPZ. E(1) values ranged from -240 mV through -670 mV
      (with TPZ having a value of -456 mV) and correlated well with the electronic
      parameter sigma for substituents at the 5-, 6-, 7-, and 8-positions. Aerobic
      cytotoxic potency showed a strong positive correlation with E(1) (i.e., electron
      withdrawing substituents increased aerobic toxicity). Hypoxic cytotoxicity also
      generally increased with increasing E(1), with a maximum (RHT up to 3.9-fold)
      seen in halo- and trifluoromethyl-substituted BTO derivatives having E(1) between
      ca. -370 to -400 mV. Analogues with high HCRs (>50) all had E(1)s in the range 
      450 to -510 mV (weakly electron-donating substituents) with the exception of the
      8-CF(3) analogue, which had an HCR of 112 against SCCVII despite a high E(1) of 
      372 mV). The results suggest that ring-A substituents in BTO analogues can be
      used to predictably vary one-electron reduction potentials and also provide a
      much better definition than previously of the optimum range of these reduction
      potentials for a desirable biological activity profile (high HCR, RHT, and
      solubility).

PMID- 12502372
TI  - Synthesis and antitumor activity of conjugates of muramyldipeptide or
      normuramyldipeptide with hydroxyacridine/acridone derivatives.
AB  - A series of MDP (muramyldipeptide) or nor-MDP (normuramyldipeptide) analogues
      modified at the C-terminus post of the molecule by a formation of an ester bond
      between the carboxylic group of isoglutamine and the hydroxyl function of the
      respective derivatives of 4-carboxamide-acridine/9-acridone or 1-nitro-9
      hydroxyalkylaminoacridines were synthesized as potential anticancer agents. The
      compounds O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl-d-gamma-isoglutaminyl)-9
      (ethylamino)-1-nitroacridine ester 3j and O-(1-O-benzyl-N-acetyl-muramyl-l-alanyl
      d-gamma-isoglutaminyl)-9-propylamino-1-nitroacridine ester 3k exhibited high in
      vitro cytotoxic activity against a panel of human cell lines, prostate cancer and
      AIDS-related lymphoma (ARL). Analogue 3j was also active in vivo in the hollow
      fiber assay. Antitumor activity of both compounds were tested in vivo against
      difference human tumor xenograft, but only analogue 3k showed in vivo activity
      against sc UACC-62 melanoma in mice.

PMID- 12502373
TI  - Synthesis and in vivo antitumor activity of poly(l-glutamic acid) conjugates of
      20S-camptothecin.
AB  - Poly-alpha-(l-glutamic acid) (PG) conjugates of 20(S)-camptothecin (1, CPT)
      displayed improved aqueous solubility compared to CPT, were stable in aqueous
      solution at neutral pH, and were potent antitumor agents in vivo. Evaluation of
      PG molecular weight, CPT loading, aqueous solubility, and CPT equivalent dosing
      with respect to in vivo antitumor potencies of various linked conjugates led to
      identification of a preferred conjugate composition.

PMID- 12502374
TI  - Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2
      cycloalkenones.
AB  - The antitumor activity of 2-crotonyloxymethyl-2-cyclohexenone (COMC-6) is not the
      result of the GSH conjugate (GSMC-6) formed inside tumor cells, as the diethyl
      ester prodrug form of GSMC-6 displays little antitumor activity with B16
      melanotic melanoma in vitro (IC(50) > 460 microM) versus COMC-6 (IC(50) 0.041
      microM) and its five- and seven-membered ring homologues. Antitumor activity
      probably results from a reactive intermediate that forms during conjugation of
      the COMCs with intracellular GSH.

PMID- 12502375
TI  - Discovery of a novel and highly potent noncompetitive AMPA receptor antagonist.
AB  - N-Acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were
      designed and synthesized as potential noncompetitive AMPA receptor antagonists on
      the basis of molecular modeling studies. Sound-induced seizure testing showed
      that this class of compounds possessed anticonvulsant properties. In particular,
      10c was more potent than talampanel (2), a noncompetitive AMPA receptor
      antagonist currently being investigated in phase III trials as an antiepileptic
      agent. Furthermore, electrophysiological studies indicated that 10c was a highly
      effective noncompetitive-type modulator of the AMPA receptor.

PMID- 12502377
TI  - Supercritical fluid extraction of all-trans-lycopene from tomato.
AB  - A procedure is proposed for the supercritical fluid extraction of all-trans
      lycopene from tomato using carbon dioxide at 40 degrees C without modifier. The
      present method minimizes the risk of degradation via isomerization and oxidation
      of health-promoting ingredients, such as lycopene. The effect of different
      experimental variables on the solvating power of the supercritical fluid was
      evaluated in terms of both the selectivity achievable in the process and the
      yield of the extraction of all-trans-lycopene. Satisfactory separations of the
      all-trans-lycopene isomers from the cis counterparts were achieved using a C(30)
      column. The obtained extract contained 88% all-trans-lycopene and 12% cis
      lycopene.

PMID- 12502378
TI  - Isolation and identification of indigestible pyroglutamyl peptides in an
      enzymatic hydrolysate of wheat gluten prepared on an industrial scale.
AB  - An enzymatic hydrolysate of wheat gluten was further digested in vitro with
      porcine pepsin and pancreatin to obtain an indigestible peptide. Indigestible
      pyroglutamyl peptide was isolated from the digest by strong cation-exchange, size
      exclusion, and reversed-phase chromatographies. The pyroglutamyl peptide was
      digested with pyroglutamate aminopeptidase, and the digest was reacted with
      phenyl isothiocyanate. The resultant phenylthiocarbamyl (PTC) peptides were
      purified by reversed-phase HPLC by using binary gradient elution with ammonium
      acetate buffer, pH 6.0, and acetonitrile. The PTC peptides were analyzed with an
      automatic peptide sequencer on the basis of the Edman degradation method with a
      modified program. Some pyroglutamyl peptides were also analyzed by fast-atom
      bombardment ionization mass spectrometry without the pyroglutamate amino
      peptidase digestion. Consequently, pyroGlu-Asn-Pro-Gln, pyroGlu-Gln-Gln-Pro-Gln,
      pyroGlu-Gln-Pro-Gln, pyroGlu-Gln-Pro-Gly-Gln-Gly-Gln, pyroGlu-Gln, pyroGlu-Gln
      Pro, pyroGlu-Ile-Pro-Gln, pyroGlu-Ile-Pro, pyroGlu-Gln-Pro-Leu, pyroGlu-Gln-Phe
      Pro-Gln, pyroGlu-Ser-Phe-Pro-Gln, pyroGlu-Phe-Pro-Gln, and pyroGlu-Gln-Pro-Pro
      Phe-Ser were identified.

PMID- 12502379
TI  - Development of an analytical scheme for simazine and 2,4-D in soil and water
      runoff from ornamental plant nursery plots.
AB  - The transport and fate of pesticides applied to ornamental plant nursery crops
      are not well documented. Methodology for analysis of soil and water runoff
      samples concomitantly containing the herbicides simazine (1-chloro-4,6
      bis(ethylamino)-s-triazine) and 2,4-D ((2,4-dichlorophenoxy)acetic acid) was
      developed in this research to investigate the potential for runoff and leaching
      from ornamental nursery plots. Solid-phase extraction was used prior to analysis
      by gas chromatography and liquid chromatography. Chromatographic results were
      compared with determination by enzyme-linked immunoassay analysis. The
      significant analytical contributions of this research include (1) the development
      of a scheme using chromatographic mode sequencing for the fractionation of
      simazine and 2,4-D, (2) optimization of the homogeneous derivatization of 2,4-D
      using the methylating agent boron trifluoride in methanol as an alternative to in
      situ generation of diazomethane, and (3) the practical application of these
      techniques to field samples.

PMID- 12502380
TI  - Chemometric classification of Apulian and Slovenian wines using 1H NMR and ICP
      OES together with HPICE data.
AB  - High-performance ion chromatography exclusion, inductively coupled plasma
      emission spectroscopy, and nuclear magnetic resonance (NMR) measurements were
      carried out in combination with chemometrics on 33 wine samples coming from three
      Slovenian wine-growing regions and from Apulia (southern Italy). The chemometric
      classification of wines according to their geographical origin was obtained with
      a nearly 100% degree of achievement. The discriminating potential of the (1)H NMR
      and of the other analytical determinations has been estimated separately. The
      best prediction of wines has been obtained with NMR data.

PMID- 12502381
TI  - SBSE-GC-ECD/FPD in the analysis of pesticide residues in Passiflora alata
      Dryander herbal teas.
AB  - Stir bar sorptive extraction (SBSE) in combination with GC-ECD/FPD analysis is
      here applied to the determination of the residues of 11 pesticides
      (hexachlorobenzene, lindane, chlorothalonil, parathion methyl, parathion ethyl,
      fenitrothion, malathion, dieldrin, alpha- and beta-endosulfan, and tetradifon) in
      herbal teas prepared with Passiflora alata Dryander spiked leaves. The method was
      optimized using spiked herbal teas in a range from 0.05 to 1 pg/microL for
      organochlorine pesticides and from 0.15 to 3 pg/microL for organophosphorus
      pesticides. The method is reproducible and repeatable with recoveries calculated
      from herbal teas prepared with spiked plant material versus spiked herbal teas,
      varying from about 30% for tetradifon to about 90% for parathion methyl and
      malathion. The limits of quantitation (LOQs) ranged from 0.017 pg/microL for
      lindane to 0.117 pg/microL for malathion.

PMID- 12502382
TI  - Molecular modeling of syringyl and p-hydroxyphenyl beta-O-4 dimers. Comparative
      study of the computed and experimental conformational properties of lignin beta-O
      4 model compounds.
AB  - As a new approach for the study of the ultrastructure of lignin, the
      conformational preferences of lignin beta-O-4 model compounds have been
      investigated by molecular modeling. The computed results have been compared with
      the experimental data (X-ray crystal structures and (3)J(H)(alpha)(H)(beta) NMR
      coupling constant values) reported in the literature. This comparison has led to
      an improved understanding of the influence of the structure, stereochemistry, and
      intramolecular H-bonding upon the conformational properties of the beta-O-4
      dimers. A large number of low-energy conformations have been predicted for the
      structures. It has also appeared that the conformational features are
      predominantly governed by local steric interactions rather than by differences in
      the H-bonding interactions. The threo and erythro forms differ significantly in
      their conformational features, with a preferential extended overall shape for the
      threo form in which the bulky aromatic groups are distant from each other.

PMID- 12502383
TI  - Molecular phylogeny and species identification of sardines.
AB  - The DNA sequence diversity of Sardina pilchardus (Walbaum, 1792) and some closely
      related species of Clupeomorpha was investigated using the mitochondrial DNA gene
      encoding cytochrome b. The nucleotide sequences of complete and partial mtDNA
      cytochrome b were determined in numerous specimens. Sequence divergence between
      species and genera was evenly distributed in the cytochrome b gene but rather
      high compared to reports for other fish species. Phylogenetic analyses on
      complete cytochrome b were used to study the relationships among the considered
      species. S. pilchardus was easily differentiated, showing a genetic distance of
      0.25 with respect to Clupeidae species and 0.26 with respect to the other
      species. A species-specific short fragment (<150 bp) was isolated by polymerase
      chain reaction (PCR) using primers designed for Clupeomorpha. A rapid and
      reliable PCR method using restriction fragment length polymorphism (RFLP) with
      two restriction enzymes (MnlI/HinfI) was optimized for unambiguous
      differentiation of S. pilchardus from the other species tested (raw and canned
      products).

PMID- 12502384
TI  - Relative quantification of N(epsilon)-(Carboxymethyl)lysine, imidazolone A, and
      the Amadori product in glycated lysozyme by MALDI-TOF mass spectrometry.
AB  - The nonenzymatic glycation of proteins by reducing sugars, also known as the
      Maillard reaction, has received increasing recognition from nutritional science
      and medical research. In this study, we applied matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to perform
      relative and simultaneous quantification of the Amadori product, which is an
      early glycation product, and of N(epsilon)-(carboxymethyl)lysine and imidazolone
      A, two important advanced glycation end products. Therefore, native lysozyme was
      incubated with d-glucose for increasing periods of time (1, 4, 8, and 16 weeks)
      in phosphate-buffered saline pH 7.8 at 50 degrees C. After enzymatic digestion
      with endoproteinase Glu-C, the N-terminal peptide fragment (m/z 838; amino acid
      sequence KVFGRCE) and the C-terminal peptide fragment (m/z 1202; amino acid
      sequence VQAWIRGCRL) were used for relative quantification of the three Maillard
      products. Amadori product, N(epsilon)-(carboxymethyl)lysine, and imidazolone A
      were the main glycation products formed under these conditions. Their formation
      was dependent on glucose concentration and reaction time. The kinetics were
      similar to those obtained by competitive ELISA, an established method for
      quantification of N(epsilon)-(carboxymethyl)lysine and imidazolone A. Inhibition
      experiments showed that coincubation with N(alpha)-acetylargine suppressed
      formation of imidazolone A but not of the Amadori product or N(epsilon)
      (carboxymethyl)lysine. The presence of N(alpha)-acetyllysine resulted in the
      inhibition of lysine modifications but in higher concentrations of imidazolone A.
      o-Phenylenediamine decreased the yield of the Amadori product and completely
      inhibited the formation of N(epsilon)-(carboxymethyl)lysine and imidazolone A.
      MALDI-TOF-MS proved to be a new analytical tool for the simultaneous, relative
      quantification of specific products of the Maillard reaction. For the first time,
      kinetic data of defined products on specific sites of glycated protein could be
      measured. This characterizes MALDI-TOF-MS as a valuable method for monitoring the
      Maillard reaction in the course of food processing.

PMID- 12502385
TI  - Improved superoxide-generating system suitable for the assessment of the
      superoxide-scavenging ability of aqueous extracts of food constituents using
      ultraweak chemiluminescence.
AB  - In the interest of developing a simple and rapid ultraweak chemiluminescence
      assay for assessing the superoxide (O(2)(-))-scavenging activities of various
      aqueous extracts of food constituents, a specific and stable O(2)(-)-generating
      system was sought. Reported herein is the obtainment for the first time of a
      specific and stable O(2)(-)-generating system consisting of methylglyoxal (MG), a
      reactive 2-oxo aldehyde and arginine, which has been shown to produce much
      steadier lucigenin-based chemiluminesence (LBCL) than the conventional
      xanthine/xanthine oxidase system running in parallel and monitoring by an
      ultraweak chemiluminescence analyzer. Upon mixing of MG and arginine in a
      phosphate-buffered saline solution, pH 7.4, steady, time-dependent increments of
      LBCL can be visually observed. The plateau of LBCL can be reached in
      approximately 10 min and retained in a steadily stable state thereafter without
      fluctuation for the next 15 min. The lucigenin-based LBCL generation was shown to
      be specific since it could be effectively inhibited by active bovine SOD, but not
      by heat-inactivated enzyme or catalase. Conversely, the xanthine/xanthine oxidase
      system can merely produce a LBCL peak rapidly but decay instantaneously. To
      illustrate the application of the proposed method for assessing the O(2)(-)
      scavenging ability of various food extracts, namely, Prunus mume (A), Lilum
      lancifolium (B), Creataegus pinnatifida (C), Tremella fuciformis (D), Fortunella
      margarita (E), and Scutellaria baicalensis (F), we used the following protocol:
      12 min after monitoring of LBCL, 1 mg/mL of each of the test compounds was added
      to the assay system and various degrees of sudden drop of LBCL values were
      observed, indicating differences in O(2)(-)-scavenging abilities exerted by these
      food extracts that can be visually compared. Consequently, the percentages of
      inhibition of LBCL versus the concentrations of a test compound can be
      constructed. It follows that the concentration needed to inhibit 50% of LBCL
      (IC(50)) of a test compound can be extrapolated from the curve. Using this
      approach, we were able to obtain the IC(50) values of various compounds to be
      tested and the order of inhibitory efficiency of the above-mentioned food
      extracts was ranked, being A > B > C > D > E > F, respectively.

PMID- 12502386
TI  - Antimicrobial and antioxidant activity of the essential oil and methanol extracts
      of Thymus pectinatus Fisch. et Mey. Var. pectinatus (Lamiaceae).
AB  - The essential oil, obtained by using a Clevenger distillation apparatus, and
      water-soluble (polar) and water-insoluble (nonpolar) subfractions of the methanol
      extract of Thymus pectinatus Fisch. et Mey. var. pectinatus were assayed for
      their antimicrobial and antioxidant properties. No (or slight) antimicrobial
      activity was observed when the subfractions were tested, whereas the essential
      oil showed strong antimicrobial activity against all microorganisms tested.
      Antioxidant activities of the polar subfraction and the essential oil were
      evaluated using 2,2-diphenyl-1-picrylhydrazyl, hydroxyl radical, superoxide
      radical scavenging, and lipid peroxidation assays. The essential oil, in
      particular, and the polar subfraction of the methanol extract showed antioxidant
      activity. The essential oil was analyzed by GC/MS, and 24 compounds, representing
      99.6% of the essential oil, were identified: thymol, gamma-terpinene, p-cymene,
      carvacrol, and borneol were the main components. An antimicrobial activity test
      carried out with fractions of the essential oil showed that the activity was
      mainly observed in those fractions containing thymol, in particular, and
      carvacrol. The activity was, therefore, attributed to the presence of these
      compounds. Other constituents of the essential oil, such as borneol, gamma
      terpinene, and p-cymene, could be also taken into account for their possible
      synergistic or antagonistic effects. On the other hand, thymol and carvacrol were
      individually found to possess weaker antioxidant activity than the crude oil
      itself, indicating that other constituents of the essential oil may contribute to
      the antioxidant activity observed. In conclusion, the results presented here show
      that T. pectinatus essential oil could be considered as a natural antimicrobial
      and antioxidant source.

PMID- 12502387
TI  - Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the
      anthocyanins.
AB  - Among ethanol extracts of 10 edible berries, bilberry extract was found to be the
      most effective at inhibiting the growth of HL60 human leukemia cells and HCT116
      human colon carcinoma cells in vitro. Bilberry extract induced apoptotic cell
      bodies and nucleosomal DNA fragmentation in HL60 cells. The proportion of
      apoptotic cells induced by bilberry extract in HCT116 was much lower than that in
      HL60 cells, and DNA fragmentation was not induced in the former. Of the extracts
      tested, that from bilberry contained the largest amounts of phenolic compounds,
      including anthocyanins, and showed the greatest 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) radical scavenging activity. Pure delphinidin and malvidin, like the
      glycosides isolated from the bilberry extract, induced apoptosis in HL60 cells.
      These results indicate that the bilberry extract and the anthocyanins, bearing
      delphinidin or malvidin as the aglycon, inhibit the growth of HL60 cells through
      the induction of apoptosis. Only pure delphinidin and the glycoside isolated from
      the bilberry extract, but not malvidin and the glycoside, inhibited the growth of
      HCT116 cells.

PMID- 12502388
TI  - Bioactivity of Backhousia citriodora: antibacterial and antifungal activity.
AB  - Backhousia citriodora products are used as bushfoods and flavorings and by the
      aromatherapy industry. The antimicrobial activity of 4 samples of B. citriodora
      oil, leaf paste, commercial tea (0.2 and 0.02 g/mL), and hydrosol (aqueous
      distillate) were tested against 13 bacteria and 8 fungi. Little or no activity
      was found to be associated with the leaf tea and hydrosol, respectively. Leaf
      paste displayed antimicrobial activity against 7 bacteria including Clostridium
      perfringens, Pseudomonas aeruginosa, and a hospital isolate of methicillin
      resistant Staphylococcus aureus (MRSA). The 4 essential oils were found to be
      effective antibacterial and antifungal agents; however, variation was apparent
      between oils that did not correlate with citral content. The antimicrobial
      activity of B. citriodoraessential oils was found to be greater than that of
      citral alone and often superior to Melaleuca alternifolia essential oil. B.
      citriodora has significant antimicrobial activity that has potential as an
      antiseptic or surface disinfectant or for inclusion in foods as a natural
      antimicrobial agent.

PMID- 12502389
TI  - Improving postharvest resistance in fruits by external application of trans
      resveratrol.
AB  - As it is well-known, one of the main problems of modern agriculture is the
      postharvest fruit losses due to pathogen's attack and natural senescence during
      storage. Well established solutions to improve this situation, such as, for
      example, storage under controlled conditions and the use of synthetic pesticides,
      are not free of problems due to human health risks and environmental effects
      caused by chemical pesticides. A new strategy to solve these problems consists of
      developing methods to improve the natural plant resistance by using, upon their
      identification, the plant's own defense molecules, in other words, applying
      methods based on the plant's own natural processes of pest suppression to control
      spoilage. This requires the identification of components of the natural defense
      response in plants, which, in turn, demands highly sensitive, fast, and versatile
      analytical methods especially for trace, nonvolatile, compounds. In this work a
      laser-based technique has been applied for screening the postharvest elicitation
      of resveratrol by Botrytis cinerea in grapes. Besides antifungal character,
      resveratrol is known to present important antioxidant properties, which could
      also have positive effects on fruit conservation during storage. Consequently,
      several experiments were carried out in which exogenous application of
      resveratrol to several fruits maintained their postharvest quality. The quality
      of both resveratrol-treated and untreated fruits has been studied by the
      assessment of the biochemical composition and sensory analysis. Indeed, the
      present work demonstrates that the external application of resveratrol does not
      alter the sensorial and biochemical properties of the fruit.

PMID- 12502390
TI  - Inhibitory activity of corn-derived bisamide compounds against alpha-glucosidase.
AB  - Bioassay guided fractionation from corn gluten meal, a byproduct of a starch
      manufacturing plant, gave N-p-coumaroyl-N'-feruloylputrescine (1) and N,N'
      diferuloylputrescine (2) as alpha-glucosidase inhibitors. Some structure-activity
      relationships were studied by comparing the inhibitory activity by preparing some
      related compounds, and it was revealed that the hydroxyl group was important for
      the inhibitory activity of bisamide alkaloids, but not the redox potential.

PMID- 12502391
TI  - Fungichromin: a substance from Streptomyces padanus with inhibitory effects on
      Rhizoctonia solani.
AB  - Streptomyces padanus strain PMS-702 is an antagonist of Rhizoctonia solani AG-4,
      the causal agent of damping-off of cabbage. Treatment of cabbage seeds with the
      culture filtrate of S. padanus strain PMS-702 was effective in reducing the
      incidence of damping-off of cabbage. The major active ingredient from the culture
      filtrate of S. padanus strain PMS-702 was purified by silica gel column
      chromatography and identified as the polyene macrolide, fungichromin, by NMR and
      mass spectral data. Bioassay studies showed that fungichromin had a strong
      antifungal activity against R. solani AG-4, and its minimum inhibitory
      concentration (over 90% inhibition) was found to be 72 microg/mL. This is the
      first report of fungichromin from S. padanus as an active ingredient for the
      control of Rhizoctonia damping-off of cabbage.

PMID- 12502392
TI  - Enterotoxigenicity and cytotoxicity of Bacillus thuringiensis strains and
      development of a process for Cry1Ac production.
AB  - Bacillus thuringiensis is indistinguishable from Bacillus cereus except for the
      production of insecticidal crystal proteins (ICPs). B. thuringiensis strains may
      show enterotoxin profiles and toxin levels similar to those of B. cereus strains
      isolated from food-poisoning cases. It is important for the food industry and
      farmers to consider that with the application of B. thuringiensis strains to
      crops, their spores may be introduced into the human food chain. In this study,
      59 B. thuringiensis strains were assayed for their hemolysin BL (HBL) using a
      BCET-RPLA kit and their cytotoxicity to Chinese hamster ovary (CHO) cells. The
      enterotoxin titer was as high as that of B. cereus diarrheal-type strain ATCC
      49064. In an attempt to obtain a food safety strain for bioinsecticide use, in
      this study, a 3.5-kb cry1Ac DNA fragment was amplified with PCR from the total
      DNA of B. thuringiensis subsp. kurstaki CCRC 11502 and cloned into the Bacillus
      expression vector pHY300PLK. The alpha-amylase promoter, amyE, was then
      introduced into the promoter region and, afterward, the recombinant plasmid
      pHYe1Ac35 was introduced into a non-enterotoxigenic and non-cytotoxic B.
      thuringiensis subsp. kurstaki Tt14 strain. The transformant, without any
      detectable enterotoxigenicity or cytotoxicity, produced Cry1Ac toxin properly,
      and its insecticidal activity against Trichoplusia ni larvae was found to be
      satisfactory.

PMID- 12502393
TI  - Effect of protease EPg222 obtained from Penicillium chrysogenum isolated from dry
      cured ham in pieces of pork loins.
AB  - The fungal protease EPg222 obtained from Penicillium chrysogenum Pg222 isolated
      from dry-cured ham, was assayed for proteolytic activity in a meat model system
      based on sterile pieces of pork loins for 32 days. Treated samples showed a
      significative reduction of total high ionic strength-soluble proteins during the
      incubation period, as compared with a control incubated without enzyme, both on
      the surface and in the depth. SDS-PAGE analysis of this protein fraction showed
      higher hydrolysis of the main myofibrillar proteins H-meromyosin, actin, and
      tropomyosin in treated samples. Non-protein and amino acidic nitrogen were
      detected in higher amounts in enzyme-added than in control pieces of loins, both
      on the surface and in the depth. Thus, addition of enzyme EPg222 to whole pieces
      of meat results in an increase of protein hydrolysis. The effect of this enzyme
      could be of great interest for stimulating proteolysis in whole dry-cured meat
      pieces.

PMID- 12502394
TI  - Structure, miscibility, and rheological characteristics of beta-casein
      monoglyceride mixed films at the air-water interface.
AB  - In this work we have used different and complementary interfacial techniques
      (surface film balance, Brewster angle microscopy, and interfacial dilatational
      rheology) to analyze the static (structure, morphology, reflectivity,
      miscibility, and interactions) and dynamic characteristics (surface dilatational
      properties) of beta-casein and monoglyceride (monopalmitin and monoolein) mixed
      films spread on the air-water interface. The static and dynamic characteristics
      of the mixed films depend on the interfacial composition and the surface
      pressure. At higher surface pressures, collapsed beta-casein residues may be
      displaced from the interface by monoglyceride molecules with important
      repercussions on the interfacial characteristics of the mixed films. From the
      frequency dependence of the surface dilatational properties, we have elucidated
      the relationships between interfacial dilatational rheology and changes in
      molecular structure, interactions, miscibility, and relaxation phenomena in
      protein-monoglyceride mixed films.

PMID- 12502395
TI  - Study of the cultivar-composition relationship in Sicilian olive oils by GC, NMR,
      and statistical methods.
AB  - The aim of this research is to find if there is direct evidence relating the
      fatty acid composition of olive oils to specific cultivars grown within a well
      limited geographical region. To group olive oils according to their own
      cultivars,(13)C high-field nuclear magnetic resonance (NMR) and gas
      chromatography (GC) were used to analyze 60 extra virgin olive oils from the same
      Italian region (southwestern Sicily) obtained from four monovarietal cultivars.
      The (13)C NMR spectrum provides information about glycerol triesters of olive
      oils, i.e., about the acyl composition of major components and about the fatty
      acids' positional distribution on the glycerol moiety. GC gives the complete
      fatty acid profile of olive oil samples. Selection of NMR and GC peaks on the
      basis of their sensitivity to the different cultivars was performed by using
      multivariate analysis of variance (MANOVA). Principal component analysis, tree
      clustering analysis, multidimensional scaling (MDS), and linear discriminant
      analysis (LDA) were then performed on the MANOVA-selected peaks. Results obtained
      from (13)C NMR and GC techniques combined with the multivariate statistical
      procedure are in good agreement and prove the usefulness of fatty acids analysis
      to group the monovarietal olive oils belonging to the same cultivars. Grouping of
      olive oils according to their cultivars occurs for particular (13)C resonances
      all belonging to fatty chains in the sn 1,3 position of the glycerol moiety.

PMID- 12502396
TI  - Folate content in strawberries (Fragaria x ananassa): effects of cultivar,
      ripeness, year of harvest, storage, and commercial processing.
AB  - Folate concentrations in strawberries and folate retention during storage and
      commercial processing of strawberries were investigated. No previous study has
      focused on the effects of cultivar, ripeness, and year of harvest of strawberries
      with respect to the folate content. This study showed the folate concentration in
      strawberries to significantly depend on all of these different factors. Total
      folate was quantified using a modified and validated radioprotein-binding assay
      with external calibration (5-CH(3)-H(4)folate). Folate content in 13 different
      strawberry cultivars varied from 335 microg/100 g of dry matter (DM) for cv.
      Senga Sengana to 644 microg/100 g of DM for cv. Elsanta. Swedish harvests from
      1999 and 2001 yielded higher folate concentrations than did the harvest from
      2000, and the grade of ripeness affected the folate content in strawberries. This
      study indicated high folate retention in intact berries during storage until 3 or
      9 days at 4 degrees C (71-99%) and also in most tested commercial products (79
      103%). On the basis of these data fresh strawberries as well as processed
      strawberry products are recommended to be good folate sources. For instance, 250
      g (fresh weight) of strawberries ( approximately 125 microg of folate) supplies
      approximately 50% of the recommended daily folate intake in various European
      countries (200-300 microg/day) or 30% of the U.S. recommendation (400
      microg/day).

PMID- 12502397
TI  - Multivariate characterization of the fatty acid profile of spanish cookies and
      bakery products.
AB  - The fatty acid compositions of 39 brands of cookies and bakery products were
      analyzed with special attention to the their trans-fatty acid content. The
      average contents (percent w/w of the total fatty acids detected) for the
      different nutritional fractions were as follows: saturated fatty acids (SFA),
      49.43% (SD = 17.04); monounsaturated fatty acids (MUFA), 32.87% (SD = 10.94);
      polyunsaturated fatty acids (PUFA), 12.48% (SD = 11.29); and trans-fatty acids
      (TFA), 5.20% (SD = 9.30), the mean fat content being 22.7% (SD = 7.4). C18:1t was
      the predominant trans isomer found in all of the analyzed samples (mean = 4.04,
      SD = 8.46). Factor analysis performed on the fatty acid profile allowed a
      meaningful classification of the samples according to the main source of fat
      employed in their elaboration. Four factors that explained 75% of the total
      variance were retained. According to the results obtained, the fat used to
      elaborate the samples was mainly composed of vegetable and animal fat, and only
      in a few samples were partially hydrogenated vegetable oils used as the main
      source of fat.

PMID- 12502398
TI  - Desmosterol: a biomarker for the efficient development of 20,25-diazacholesterol
      as a contraceptive for pest wildlife.
AB  - 20,25-Diazacholesterol is being evaluated as a contraceptive for the nonlethal
      control of avian and mammalian wildlife pests. The identification of an analyte
      in blood which was highly correlated with absorbed dose and efficacy is valuable
      for determining effective formulations and dosing variables. Such an analyte or
      biomarker is also valuable for determining the percentage of pest populations
      that consume an effective dose of the active ingredient in the field. HPLC
      analyses of blood collected from dosed animals failed to detect 20,25
      diazacholesterol but indicated that levels of free cholesterol and related
      compounds were affected by 20,25-diazacholesterol absorption. The greatest
      percent change in chromatographic peak area associated with 20,25
      diazacholesterol administration was observed for desmosterol, a cholesterol
      precursor. 20,25-Diazacholesterol appeared to block the conversion of desmosterol
      to cholesterol, resulting in an elevated concentration of the precursor. The
      elevation of blood desmosterol levels is being used as an indicator of 20,25
      diazacholesterol absorption and to facilitate the development of a 20,25
      diazacholesterol-based contraceptive for pest wildlife.

PMID- 12502399
TI  - Fate of isoxaflutole in soil under controlled conditions.
AB  - Isoxaflutole (IFT, 5-cyclopropyl-1,2-oxazol-4yl-alpha,alpha,alpha-trifluoro-2
      mesyl-p-tolyl ketone) is a new pre-emergence proherbicide used in maize and
      sugarcane. Its two main derivatives are a diketonitrile derivative, 2-cyano-3
      cyclopropyl-1-(2-methanesulfonyl-4-trifluoromethylphenyl)propane-1,3-dione,
      called DKN, and a benzoic acid derivative, 2-methanesulfonyl-4
      trifluoromethylbenzoic acid, called BA. Few data are available of the factors
      influencing the degradation of IFT in soil, and the purpose of the present work
      was to determine the relative importance of, and factors affecting, the
      degradation of IFT in soil. Experiments were conducted on five soils with
      distinct physicochemical characteristics, at different temperatures and moisture
      contents in biotic and abiotic conditions. The isomerization of IFT to DKN is
      rapid, increasing with higher moisture contents and higher temperatures. It
      depends strongly on pH and is governed by chemical processes. The degradation of
      DKN to BA appeared to be essentially due to the biological activity of the soil.

PMID- 12502400
TI  - Synthesis and antifeedant activity of new oxadiazolyl 3(2H)-pyridazinones.
AB  - A total of 20 new compounds containing the oxadiazolyl 3(2H)-pyridazinone moiety
      were synthesized. The structures of all the compounds were confirmed by (1)H NMR,
      IR, MS, and elemental analysis. Their insect antifeedant activities against
      Asiatic corn borer Ostrinia furnacalis (Guenee) were examined and compared with
      commercial azadirachtin. The compounds exhibited significant levels of activity.
      The feeding deterrency values of IIIa,j were 57% and 51% at 500 mg/kg
      concentration, respectively.

PMID- 12502401
TI  - Preparation of antibodies and development of an enzyme-linked immunosorbent assay
      for determination of dealkylated hydroxytriazines.
AB  - The development of an indirect competitive enzyme-linked immunosorbent assay
      (ELISA) for dealkylated hydroxytriazines is reported here for the first time. The
      assay uses polyclonal antibodies raised against N-(4-amine-6-hydroxy
      [1,3,5]triazin-2-yl)-4-aminobutanoic acid (hapten 2g) conjugated to keyhole
      limpet hemocyanin by the active ester method. The immunizing hapten was
      synthesized by first introducing the amino group to the triazine ring in a
      protected form in order to increase its solubility in organic media. Subsequent
      steps consisted of reacting this compound with an appropriate spacer arm,
      followed by removal of the protecting group in acidic media. The resulting assay
      uses a homologous competitor hapten coupled to conalbumin by the mixed anhydride
      method. Coating antigens prepared using a homologous covalent coupling procedure
      failed to produce competitive immunoassays. The assay tolerates media with high
      ionic strength (up to 70 mS cm(-)(1)) and basic pH values (7.5-9.5 units). Under
      the optimized conditions, this ELISA is specific for dealkylated
      hydroxytriazines, reaching suitable limits of detection.

PMID- 12502402
TI  - Organic matter effects on phase partition of 1,3-dichloropropene in soil.
AB  - The fumigant 1,3-dichloropropene (1,3-D), in combination with chloropicrin, is
      considered a major replacement to methyl bromide (MeBr). This study was conducted
      to better understand phase partitioning of 1,3-D and the role of organic matter
      in its adsorption to soil. Partition of 1,3-D between air and water (K(H)), and
      between soil and water (K(f)), was determined by quantifying the concentration in
      both phases upon equilibrium. At 20 degrees C, the K(H) values of (Z)- and (E)
      1,3-D were 0.052 and 0.033, respectively. In four California and Florida soils,
      the K(f) values of 1,3-D isomers ranged from 0.39 to 8.55, and the K(oc) values
      ranged from 18 to 60. The relatively high K(H) and low K(f) imply that 1,3-D is
      highly mobile in most soils after subsurface application. Adsorption of 1,3-D in
      native soils and soils amended with manure compost increased with increasing soil
      organic matter content. This suggests that organic wastes may be applied to soil
      to increase 1,3-D adsorption, thus reducing its potential for offsite movement.

PMID- 12502403
TI  - The persistence and degradation of chlorothalonil and chlorpyrifos in a cranberry
      bog.
AB  - The effect of a spray-tank adjuvant on the persistence, distribution, and
      degradation of two pesticides, chlorothalonil and chlorpyrifos, was studied in a
      commercial cranberry bog. Pesticides were applied according to label instructions
      to cranberry plants in paired plot studies. Dislodgeable foliar and whole fruit
      residues of both pesticides and several degradation products were assessed over a
      growing season. Residues were also assessed in soil samples collected at fruit
      harvest. Adjuvant increased both fruit and foliar residues but did not
      significantly alter the dissipation rate or metabolism of either pesticide. The
      dissipation of dislodgeable foliar chlorothalonil and chlorpyrifos residues
      followed first-order kinetics, with estimated half-lives of 12.7 and 3.5 d,
      respectively. All residue levels on harvested fruit were well below the current
      U.S. EPA tolerances for fresh cranberries. Chlorothalonil (58%) was the major
      residue in fruit at harvest (76 d post-chlorothalonil application), with 4
      hydroxy-2,5,6-trichloroisophthalonitrile and 1,3-dicarbamoyl-2,4,5,6
      tetrachlorobenzene accounting for 26% and 6% of the total residues, respectively.
      Degradation products accounted for 88% of the total chlorothalonil residues in
      soil at fruit harvest. The products 1,3-dicarbamoyl-2,4,5,6-tetrachlorobenzene, 1
      carbamoyl-3-cyano-4-hydroxy-2,5,6-trichlorobenzene, 2,5,6-trichloro-4
      methylthioisophthalonitrile, and 2,4,5-trichloroisophthalonitrile have not been
      previously identified in cranberry bog environments. Chlorpyrifos was detected in
      fruit at harvest (62 d post-chlorpyrifos application), but no metabolites were
      found. Chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol, however, were detected
      in earlier fruit samples and in foliage and soil samples.

PMID- 12502404
TI  - Mobility and degradation of the herbicide imazosulfuron in lysimeters under field
      conditions.
AB  - The mobility and degradation of imazosulfuron, labeled with carbon-14 at the
      imidazole ([imi-(14)C]imazo) or pyrimidine ring ([pyr-(14)C]imazo), in lysimeters
      with 1 m(2) surface and 110 cm depth were investigated for three years. One
      lysimeter was treated with [imi-(14)C]imazo in two successive years at the rate
      of 50 g of active ingredient (ai)/ha each. The other two lysimeters were treated
      once with [pyr-(14)C]imazo and a mixture (1:1, w/w) of the two labeled
      imazosulfurons, respectively (50 g of ai/ha). In the first and second years of
      monitoring, the yearly mean concentration of (14)C in the leachate water was
      <0.10 microg/L in each lysimeter. Although in the third year the concentration of
      (14)C in the leachate water was 0.17 microg/L for the lysimeter treated twice
      with [imi-(14)C]imazo, the concentration of imazosulfuron and its degradation
      products in the leachate water ranged from 0.01 to 0.06 microg/L. At the study
      termination, the main portion of (14)C recovered was found in the upper 30 cm
      soil layer in each lysimeter, and no (14)C was detected below a depth of 50 cm.
      These findings indicated that imazosulfuron and its degradation products in soils
      translocated into groundwater only slightly.

PMID- 12502405
TI  - Retention and extractability of phenol, cresol, and dichlorophenol exposed to two
      surface soils in the presence of horseradish peroxidase enzyme.
AB  - The retention of phenol, o-cresol, 2,4-dichlorophenol (DCP), and their peroxidase
      catalyzed polymerization products was evaluated on two surface soils. The
      extractability of the parent solutes and their polymerization products was also
      investigated. (14)C-Labeled radioisotopes were used to quantify the contaminant
      retained on soil as water-extractable, methanol-extractable, humic/fulvic (HA/FA)
      acid-bound, and soil/humin bound. Between 2 and 20% of the solute retained on
      soil after a 7-day contact period remained bound to the HA/FA and soil/humin
      components in unamended soils; in the presence of peroxidase this amount was as
      high as 40-75%. The alkali-extractable HA/FA component contained the largest
      fraction of radioactivity in peroxidase-amended soils. Whereas the soil organic
      matter content was the predominant factor controlling the extent of sorption of
      the parent phenols, the clay content and particle surface area appeared to
      contribute to the retention of the polymerization products. High molecular weight
      oligomers produced during peroxidase-mediated polymerization of phenols associate
      strongly with soil components and are likely incorporated into the soil organic
      matter via oxidative coupling reactions.

PMID- 12502406
TI  - Experimental and modeling studies showing the effect of lipid type and level on
      flavor release from milk-based liquid emulsions.
AB  - The purpose of this work was to study two key parameters of the lipid phase that
      influence flavor release-lipid level and lipid type-and to relate the results to
      a mass balance partition coefficient-based mathematical model. Release of 10
      volatile compounds from milk-based emulsions at 10, 25, and 50 degrees C was
      monitored by 1-min headspace sampling with a solid-phase microextraction fiber,
      followed by GC-MS analysis. As compared to the observations for milk fat,
      changing to a lipophilic lipid (medium-chain triglycerides, MCT) and adding a
      monoglyceride-based surfactant did not influence the volatiles release. However,
      increasing the solid fat content was found to increase the release. At 25 degrees
      C, and even more so at 10 degrees C, concurrent with an increase in their solid
      fat content, hydrogenated palm fat emulsions showed increased flavor release over
      that observed for emulsions made with coconut oil, coconut oil with surfactant,
      milk fat, and MCT. However, at 50 degrees C, when hydrogenated palm fat emulsions
      had zero solid fat content, there was no difference in flavor release from that
      observed for milk fat emulsions. Varying milk fat at nine levels between 0 and
      4.5% showed a systematic dependence of the release on the lipid level, dependent
      on compound lipophilicity. Close correlations were found between the experimental
      and model predictions with lipid level and percent liquid lipid as variables.

PMID- 12502407
TI  - Linalool in orange juice: origin and thermal stability.
AB  - Linalool concentrations were determined in juice from three groups of 60 Valencia
      oranges using pentane:ether extraction and high-resolution capillary GC. The
      outer peel (flavedo) was removed from one group. The other two groups retained
      their peel intact. Juice was extricated from the halved fruits of the flavedo
      less group and from one of the peel-intact groups using a hand reamer. A peel
      cutting/macerating juice extractor was used for the other peel-intact group.
      Linalool concentrations were 0.004 mg/L in peeled fruit juice and 0.020 and 0.106
      mg/L for hand-reamed and mechanically extracted peel-intact juice, respectively.
      Juice from peeled fruit contained significantly (P < 0.05) less linalool than
      peel-intact juice. Approximately 80% of the total juice linalool content was
      associated with peel using reamer design, and 96% was associated with peel
      cutting/macerating design. Linalool increased with increasing peel oil levels;
      however, the increases were not proportionate. Since all commercial juices are
      mechanically extracted, the vast majority of linalool in commercial orange juice
      originates from the peel and not from the juice vesicle cytoplasm. Juice from
      peel-macerated, mechanically extracted fruit increased from 0.106 to 0.134 mg/kg
      after thermal processing, whereas juice from reamer extraction was essentially
      unchanged.

PMID- 12502408
TI  - Headspace solid-phase microextraction method for the study of the volatility of
      selected flavor compounds.
AB  - Changes in the volatility of selected flavor compounds in the presence of
      nonvolatile food matrix components were studied using headspace solid-phase
      microextraction (HS-SPME) combined with GC-MS quantification. Time-dependent
      adsorption profiles to the SPME fiber and the partition coefficients between
      different phases were obtained for several individual volatiles, showing that HS
      SPME analysis with a short sampling time can be used to determine the "true"
      headspace concentration at equilibrium between the headspace and a sample matrix.
      Equilibrium dialysis followed by HS-SPME/GC-MS was carried out to confirm the
      ability of HS-SPME extraction for monitoring the free volatile compounds in the
      presence of proteins. In particular, a short sampling time (1 min) avoided
      additional extraction of volatiles bound to the protein. Interactions between
      several selected flavor compounds and nonvolatile food matrix components [beta
      lactoglobulin or (+)-catechin] were also studied by means of HS-SPME/GC-MS
      analysis. The volatility of ethyl hexanoate, heptanone, and hexanal was
      significantly decreased by the addition of beta-lactoglobulin compared to that of
      isoamyl acetate. Catechin decreased the volatility of ethyl hexanoate and hexanal
      by 10-20% and increased that of 2-heptanone by approximately 15%. This study
      indicates that HS-SPME can be a useful tool for the study of the interactions
      between volatile compounds and nonvolatile matrix components provided the kinetic
      and thermodynamic behavior of the volatiles in relation to the fiber chosen for
      the studies is carefully considered.

PMID- 12502409
TI  - Effects of rootstock on the composition of bergamot (Citrus bergamia Risso et
      Poiteau) essential oil.
AB  - This paper reports the composition of bergamot oils obtained from plants grafted
      on the following rootstocks: sour orange, Carrizo citrange, trifoliate orange,
      Alemow, Volkamerian lemon, and Troyer citrange. The aim of this study is to
      evaluate the possibility of using rootstocks other than sour orange, checking
      their effect on the composition of the essential oil. Results are reported for
      analysis of 203 bergamot oils during the years 1997-1998, 1998-1999, and 1999
      2000. The oils were analyzed by HRGC and HRGC/MS; 78 components were identified,
      and the results were in agreement with those reported in the literature for the
      Calabrian bergamot oils obtained from industry. Because of the quality of their
      essential oils, Alemow and Volkamerian lemon can be considered as substitutes for
      sour orange rootstocks.

PMID- 12502410
TI  - The question of high- or low-temperature glass transition in frozen fish.
      Construction of the supplemented state diagram for tuna muscle by differential
      scanning calorimetry.
AB  - The thermal behavior of fresh tuna muscle, rehydrated freeze-dried tuna muscle,
      and tuna sarcoplasmic protein fraction was studied by three types of differential
      scanning calorimetry (DSC): conventional DSC, alternating DSC, and sensitive
      micro-DSC. The relationship between glass transition temperature, T(g), and water
      content was established. Only a low-temperature glass transition was detected for
      fresh tuna and freeze-dried tuna rehydrated to high water contents, whereas for
      sarcoplasmic protein fraction both a low-temperature and an apparent high
      temperature glass transition were detected for samples of high water content.
      Construction of the supplemented state diagrams for whole tuna muscle and for
      tuna sarcoplasmic protein fraction confirmed the low-temperature transition to be
      glass transition of the maximally freeze-dehydrated phase. The apparent upper
      transition of sarcoplasmic protein fraction was shown not to be a glass
      transition but rather to originate from the onset of melting of ice, and the
      temperature of this event should be denoted T(m)'. The glass transition
      temperature and the concentration of the maximally freeze dehydrated tuna muscle
      are -74 degrees C and 79% (w/w), respectively.

PMID- 12502411
TI  - Enzymic release of reducing sugars from oat hulls by cellulase, as influenced by
      Aspergillus ferulic acid esterase and trichoderma xylanase.
AB  - Hydroxycinnamic acids, mainly ferulic and p-coumaric acids, are believed to be
      inhibitory to ruminal biodegradability of complex cell wall materials such as oat
      hulls. Previous studies have shown that a novel enzyme, Aspergillus ferulic acid
      esterase, and Trichoderma xylanase act synergistically to break the ester linkage
      between ferulic acid and the attached sugar of feruloyl polysaccharides,
      releasing ferulic acid from oat hulls. In this paper, we examined the enzymic
      release of reducing sugars from oat hulls by the actions of individual enzymes
      (Aspergillus ferulic acid esterase at 13 mU, 6.4 U, and 4678.4 U/assay; cellulase
      at 20 levels, ranging from 7.8 mU to 2772.7 U/assay; Trichoderma xylanase at 20
      levels, ranging from 7.8 mU to 4096 U/assay) and by the combined action of
      cellulase at six levels (62.5 mU, 2 U, 16 U, 128 U, 1024 U, and 2772.7 U/assay),
      Aspergillus ferulic acid esterase at 13 mU/assay, and Trichoderma xylanase at two
      levels (1 U and 256 U/assay). The amount of total acid-extractable reducing
      sugars in the oat hulls used in this study was 793.8 +/- 8.0 microg/mg. The
      results show that after a 24-h incubation with Aspergillus ferulic acid esterase
      alone, no reducing sugars were observed to be released from oat hulls. With
      cellulase as the sole enzyme, as the concentration increased from 7.8 mU to
      2772.7 U/assay, the release of reducing sugars increased (P < 0.01) from 0 to 39%
      of the total present, with the highest release at 512 U/assay. With Trichoderma
      xylanase alone, as the concentration increased from 7.8 mU to 4096 U/assay, the
      release of reducing sugars increased (P < 0.01) from 4.9 to 33%, with the highest
      release at 2048 U/assay. When incubated together with Trichoderma xylanase (1 U
      or 256 U/assay) and Aspergillus ferulic acid esterase (13 mU/assay), cellulase at
      all six levels (62.5 mU, 2 U, 16 U, 128 U, 1024 U and 2772.7 U/assay)
      significantly increased the release of reducing sugars (P < 0.01) from 8 to 69%.
      These results indicate that the synergistic interaction between Aspergillus
      ferulic acid esterase and Trichoderma xylanase on the release of ferulic acid
      from feruloyl polysaccharides of oat hulls makes the remainder of the
      polysaccharides open for further hydrolytic attack and facilitates the
      accessibility of the main chain of polysaccharides to cellulase. This action
      extends the cell wall hydrolysis, thus releasing a higher yield of reducing
      sugars. Such enzymic pretreatment of oat hulls may provide a unique advantage to
      rumen microorganisms for the biodegradation of the complex cell walls of
      byproduct feeds such as oat hulls.

PMID- 12502412
TI  - Kinetics of hydrolysis of fructooligosaccharides in mineral-buffered aqueous
      solutions: influence of pH and temperature.
AB  - High-performance anion exchange chromatography coupled with a pulsed amperometric
      detection system (HPAEC-PAD) was used to evaluate the extent of chemical
      hydrolysis of three fructooligosaccharides (FOS) including 1-kestose (beta-D-Fru
      (2-->1)(2)-alpha-D-glucopyranoside, GF2), nystose (beta-D-Fru-(2-->1)(3)-alpha-D
      glucopyranoside, GF3), and fructofuranosylnystose (beta-D-Fru-(2-->1)(4)-alpha-D
      glucopyranoside, GF4). A kinetic study was carried out at 80, 90, 100, 110, and
      120 degrees C in aqueous solutions buffered at pH values of 4.0, 7.0, and 9.0.
      Under each experimental condition, the determination of the respective amounts of
      reactants and hydrolysis products showed that FOS hydrolysis obeyed pseudo-first
      order kinetics as the extent of hydrolysis, which decreased at increasing pH
      values, increased with temperature. The three oligomers were found to be degraded
      mainly under acidic conditions, and at the highest temperature value (120 degrees
      C), a quick and complete acid degradation of each FOS was observed. Using the
      Arrhenius equation, rate constants, half-life values, and activation energies
      were calculated and compared with those obtained from sucrose under the same
      experimental conditions. It appeared that the hydrolysis of FOS took place much
      more easily at acidic pH than at neutral or basic pH values.

PMID- 12502413
TI  - Effects of water activity and lipid addition on secondary structure of zein in
      powder systems.
AB  - The effects of water activity (A(w)) and lipid addition on the secondary
      structure of powdery zein were investigated using Fourier transform infrared
      spectroscopy. Two fatty acid esters, i.e., the linolenic and eicosapentaenoic
      acid ethyl esters (LAE and EPE), were mixed with the zein powder. The powders
      were stored in the "dry" state (with silica gel) and the "humid" state (A(w) =
      0.9). The powdery zein without the lipids was shown to have a high content of the
      intermolecular hydrogen-bonded beta-sheet in the "dry" state, indicating the
      presence of protein aggregates. An increase in A(w) induced a decrease in this
      beta-sheet, concomitant with increases in the alpha-helix and beta-turn
      structures. The addition of LAE caused decreases in the alpha-helix and
      intermolecular hydrogen-bonded beta-sheet of zein when the powder was stored in
      the "humid" state, suggesting the strong interaction of LAE and zein molecules.
      However, LAE did not affect the secondary structure of zein in the "dry" state.
      The addition of EPE hardly influenced the secondary structure of zein,
      irrespective of A(w). These results are discussed in relation to the
      antioxidative activity of zein in the powder system, which had studied
      previously.

PMID- 12502414
TI  - Effects of Ca2+ and sulfhydryl reductant on the polymerization of soybean
      glycinin catalyzed by mammalian and microbial transglutaminases.
AB  - Two types of transglutaminases (TGases), Ca(2+)-dependent TGase derived from
      guinea pig liver (GTGase) and Ca(2+)-independent TGase derived from a variant of
      Streptoverticillium mobaraense (MTGase), were used to study the cross-linking of
      soybean 11S globulin (glycinin). The effects of sulfhydryl reductant
      (dithiothreitol, DTT) and Ca(2+) on the conformation and TGase-catalyzed
      polymerization of glycinin were investigated. The conformational change of
      glycinin was probed by spectral methods. The degree of cross-linking and the
      polymer (aggregate) formation were analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and dynamic light scattering, respectively.
      Addition of DTT stimulated the TGase-catalyzed cross-linking reactions without
      destroying the secondary and tertiary structure of glycinin but did not influence
      the polymer or aggregate formation. It was found that Ca(2+) caused the formation
      of larger size polymers at lower concentrations, while it suppressed the
      polymerization at higher concentrations. In addition, the cross-linking behaviors
      of glycinin were shown to be different between MTGase- and GTGase-catalyzed
      systems.

PMID- 12502415
TI  - Effects of genotype, environment, and postharvest storage on the total ascorbate
      content of potato (Solanum tuberosum) tubers.
AB  - The total ascorbate content of potato tubers from 33 Solanum tuberosum genotypes
      grown at three geographically diverse sites in Europe in each of two years was
      determined immediately postharvest and after approximately 4 months of storage at
      4 degrees C. Statistically significant differences in total ascorbate
      concentration were observed between genotypes both at harvest and after storage.
      In all genotypes, the levels of ascorbate decreased during storage. These results
      are discussed in terms of their implications for diet and health as well as in
      terms of breeding for improved vitamin C content in potatoes.

PMID- 12502416
TI  - Eggshell matrix proteins as defense mechanism of avian eggs.
AB  - This study focused on the role of eggshell matrix proteins as a function of
      potential natural antimicrobial defenses of avian eggs. The electrophoretic
      profile of SDS-PAGE showed that the soluble eggshell matrix proteins had three
      major bands of 15 000, 36 000, and 66 000 and several minor bands comprising 17
      000, 25 000, 30 000, and 75 000, while insoluble matrix proteins were consisting
      of various bands comprising at least 16 distinct migration bands between 10 000
      and 200 000. Three bacteria species, Pseudomonas aureginosa, Bacillus cereus, and
      Staphylococcus aureus, were found to be inhibited in the presence of soluble
      eggshell matrix proteins (100 microg/mL). On the other hand, Escherichia coli and
      Salmonella enteritidis were weakly inhibited at only an early stage of incubation
      time (up to 4 h). Scanning electron microscopy revealed that eggshell matrix
      proteins might interact and disrupt the membrane integrity of bacteria. The
      present study clearly indicated that avian eggshell matrix proteins possess a
      potential of novel antimicrobial defensin mechanism.

PMID- 12502417
TI  - Comparative studies on some quality attributes of firm tofu sterilized with
      traditional and autoclaving methods.
AB  - An innovative retort cooking method was developed for firm tofu sterilization to
      replace the traditional hydrogen peroxide treatment. The caramelized firm tofu
      was sterilized by autoclaving at 105 degrees C for 20 min, which led to a 3 log
      cycle reduction of total plate count. Shelf life of the processed firm tofu was
      extended at least 3 months. As compared with chemical treatment, thermal
      treatment degraded total and individual isoflavones to a lesser extent, and only
      minor changes were observed. The percent DPPH free radical scavenging capacity of
      autoclaved firm tofu was significantly higher than that of the hydrogen peroxide
      treated samples. Even after prolonged heat treatment, the three-dimensional
      network structure of the autoclaved firm tofu did not change significantly.
      Texture profile analysis and sensory evaluation confirmed autoclaved firm tofu to
      be acceptable.

PMID- 12502418
TI  - Application of the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical
      cation assay to a flow injection system for the evaluation of antioxidant
      activity of some pure compounds and beverages.
AB  - The 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation
      (ABTS(*)(+)) assay was adapted to a flow injection (FI) system to obtain a
      sensitive and rapid technique for the monitoring of antioxidant activity of pure
      compounds and complex matrixes, such as beverages and food extracts. The FI
      system includes a HPLC pump that flows the mobile phase (a solution of ABTS(*)(+)
      in ethanol) through a 20 microL loop injector, a single bead string reactor
      filled with acid-washed silanized beads, a delay coil and a photodiode array UV
      visible detector. The technique was very sensitive, with limits of detection and
      of quantification of 4.14 and 9.29 micromol of Trolox/L, respectively, and
      demonstrated high repeatability and reproducibility. The proposed technique was
      then applied to the evaluation of the antioxidant activity of some pure
      compounds, demonstrating good agreement with published data obtained by the
      original spectrophotometric ABTS(*)(+) assay. Finally, the total antioxidant
      activity of 10 beverages was determined by both the proposed and the original
      method. The values ranged from 0.09 mmol L(-)(1) for cola to 49.24 mmol L(-)(1)
      for espresso coffee and did not result significantly different from those
      obtained by the original spectrophotometric ABTS(*)(+) assay (Student's paired t
      test: t = 1.4074, p = 0.1929). In conclusion, the proposed FI technique seems
      suitable for the direct, rapid and reliable monitoring of total antioxidant
      activity of pure compounds and beverages and, due to the ability to operate in
      continuous, it allows the analysis of about 30 samples h(-)(1) making the assay
      particularly suitable for large screening of total antioxidant activity in food
      samples.

PMID- 12502419
TI  - Role of hydrocolloids in the creaming of oil in water emulsions.
AB  - The influence of guar gum and xanthan gum on the creaming of 10% oil in water
      emulsions has been investigated. The presence of very low concentrations of the
      polysaccharides (typically < approximately 0.075%) was found to induce depletion
      flocculation of the emulsion droplets and increased the rate of creaming.
      However, at higher polysaccharide concentrations (typically > approximately 0.1%)
      the creaming rate was reduced due to the increased viscosity of the aqueous
      phase. For most systems a delay period was noted before creaming started, which
      was found to be dependent on the zero shear viscosity of the continuous phase and
      independent of polysaccharide type. The delay period increased significantly at
      zero shear viscosities approaching 1 Pa s. A mathematical model has been used to
      fit the creaming rate profiles and a simple exponential relationship obtained
      between delay time and polysaccharide concentration.

PMID- 12502420
TI  - Composition of the water-soluble fraction of different cheeses.
AB  - Volatile and nonvolatile compounds present in the water-soluble fraction (WSF)
      and water-soluble fraction with molecular weight lower than 1000 Da (WSF < 1000
      Da) of six Spanish cheeses, Cabrales, Idiazabal, Mahon, Manchego, Roncal, and a
      goat's milk cheese, were analyzed. Different nitrogen fractions (determined by
      Kjeldahl method), caseins (by capillary electrophoresis), peptides and amino
      acids (by HPLC), and volatile components (by dynamic headspace coupled to GC-MS)
      as well as mineral content in the cheese fractions were analyzed and compared.
      The different nitrogen and volatile compounds identified in the WSF were
      characteristic of each cheese variety. Cabrales cheese displayed the highest
      content of free amino acids and the highest quantity and variety of volatile
      compounds. The WSF < 1000 Da fraction was less representative, especially for
      volatile compounds, as some of the components were lost in the ultrafiltration.
      Alcohols were better recovered than ketones and esters.

PMID- 12502421
TI  - Isolation and structural characterization of new acylated anthocyanin-vinyl
      flavanol pigments occurring in aging red wines.
AB  - Three newly formed pigments were detected and isolated from a 2-year-old Port
      wine through TSK Toyopearl HW-40(S) gel column chromatography and characterized
      by UV-visible spectrophotometry, NMR, and mass spectrometry (ESI/MS). (1)H NMR
      and (13)C NMR data for these pigments obtained using 1D and 2D NMR techniques
      (COSY, NOESY, gHSQC, and gHMBC) are reported for the first time. The structure of
      the pigments was found to correspond to the vinyl cycloadducts of malvidin 3
      coumaroylglucoside bearing either a procyanidin dimer or a flavanol monomer ((+)
      catechin or (-)-epicatechin). Additionally, conformational analysis was performed
      for one of these newly formed pigment using computer-assisted model building and
      molecular mechanics. A chemical nomenclature is proposed to unambiguously name
      this new family of anthocyanin-derived pigments.

PMID- 12502422
TI  - Effect of cholecalciferol-enriched hen feed on egg quality.
AB  - Eggs are one of the most important sources of vitamin D in the human diet, and
      their vitamin D content can be further increased by adding more vitamin D to hen
      feed. To investigate this issue more closely, we performed two feeding
      experiments. In both, zero egg samples were collected while the hens were fed
      regular feeds with a vitamin D content of 1720 or 4280 IU/kg. In experiment 1,
      egg samples were collected 2, 4, 7, 9, 11, 13, 16, 23, and 30 days after
      beginning the high-cholecalciferol (11 200 IU/kg) feeding period. In experiment
      2, samples were collected 2, 4, 6, 8, 13, 28, 56, 84, 112, 140, and 168 days
      after beginning the high-cholecalciferol (12 000 IU/kg) diet. The egg samples
      were then assayed for their cholecalciferol content, and some samples, also for
      the presence of 25-hydroxycholecalciferol by an HPLC method. Further, the vitamin
      D-fortified eggs were compared with the controls by a sensory evaluation, by
      conducting fatty acid and functional analyses (emulsion capacity, gel forming
      capacity, foaming properties) and by measuring eggshell strength. Because vitamin
      D can be toxic in high doses, we also performed histopathological tests on the
      hens at the end of experiment 2. The top cholecalciferol contents in egg yolk
      (ca. 30 microg/100 g) were reached 8-13 days from starting the high
      cholecalciferol diet. After 112 days feeding the cholecalciferol content
      gradually decreased to ca. 22 microg/100 g. When added to eggs as described
      above, vitamin D did not affect their sensory or functional properties or their
      fatty acid composition. Moreover, the cholecalciferol levels used in this study
      appeared not to affect eggshell strength or to be harmful for hens.

PMID- 12502423
TI  - ADP ribosylation factor regulates metabolism and antioxidant capacity of
      transgenic potato tubers.
AB  - In our recent studies we have evidenced that repression of ADP-ribosylation
      factor (ARF) in potato plants results in 14-3-3 gene activation. The significant
      alteration in plant phenotype and in carbohydrate content clearly indicates that
      there may also be changes in other metabolite syntheses. In this paper we present
      the data on contents of compounds, occurring in transgenic potato tubers from
      field trial, known to be important for the human diet. We also determine which of
      the ARF-antisense plant features resulted from ARF repression. This determination
      was accomplished by the analysis of ARF-antisense plants transformed with cDNA
      encoding 14-3-3 protein in reverse orientation. The sucrose accumulation and the
      decrease in glycoalkaloids level were found to be characteristic features of all
      transgenic plants. The increase in antioxidant capacity of transgenic potato
      tubers should also be pointed out. The analysis of fat from modified potato
      tubers revealed a nutritionally valuable composition of fatty acids, including
      the significant increase of linoleic acid level.

PMID- 12502424
TI  - Antioxidant activity and characterization of volatile constituents of Taheebo
      (Tabebuia impetiginosa Martius ex DC).
AB  - Volatiles were isolated from the dried inner bark of Tabebuia impetiginosa using
      steam distillation under reduced pressure followed by continuous liquid-liquid
      extraction. The extract was analyzed by gas chromatography and gas chromatography
      mass spectrometry. The major volatile constituents of T. impetiginosa were 4
      methoxybenzaldehyde (52.84 microg/g), 4-methoxyphenol (38.91 microg/g), 5-allyl
      1,2,3-trimethoxybenzene (elemicin; 34.15 microg/g), 1-methoxy-4-(1E)-1
      propenylbenzene (trans-anethole; 33.75 microg/g), and 4-methoxybenzyl alcohol
      (30.29 microg/g). The antioxidant activity of the volatiles was evaluated using
      two different assays. The extract exhibited a potent inhibitory effect on the
      formation of conjugated diene hydroperoxides (from methyl linoleate) at a
      concentration of 1000 microg/mL. The extract also inhibited the oxidation of
      hexanal for 40 days at a level of 5 microg/mL. The antioxidative activity of T.
      impetiginosa volatiles was comparable with that of the well-known antioxidants,
      alpha-tocopherol, and butylated hydroxytoluene.

PMID- 12502425
TI  - Antioxidant, prooxidant, and cytotoxic activities of solvent-fractionated
      dandelion (Taraxacum officinale) flower extracts in vitro.
AB  - This study was conducted to investigate the chemical antioxidant and bioactive
      properties of the water (WF) and ethyl acetate fractions (EAF) derived from
      dandelion (Taraxacum officinale) flower extract (DFE). HPLC analysis showed the
      presence of both luteolin and luteolin 7-glucoside in the DFE, which contributed
      to noted in vitro antioxidant and Caco-2 cell cytotoxic activities. Both WF and
      EAF of DFE exhibited free radical scavenging activities in a stable 2,2-diphenyl
      1-picrylhydrazyl radical model and reduced the breakage of supercoiled DNA strand
      induced by both non-site-specific and site-specific hydroxyl radical. Oxidation
      of structured phosphatidylcholine liposome induced by peroxyl radical was reduced
      in the presence of both EAF and WF. EAF had greater (p < 0.05) affinity to
      scavenge peroxyl radical than WF, as measured by the formation of conjugated
      diene. At low concentration, prooxidant activity of both fractions was observed
      in Cu(2+)-induced structured liposome and hLDL oxidation models, thus indicating
      that the reducing power of the DFE had resulted in generation of reactive cuprous
      ion. However, at high concentrations the EAF did not promote oxidation in the
      presence of Cu(2+), suggesting that the free radical scavenging activity of this
      fraction was sufficient to minimize the potential oxidative mechanism attributed
      to the metal ion reducing activity associated with prooxidant activity.

PMID- 12502426
TI  - Effect of a polyphenols-enriched chardonnay white wine in diabetic rats.
AB  - A Chardonnay white wine enriched in polyphenols was obtained by modification of
      winemaking and characterized by its enrichment in total polyphenolic content
      (1346 mg/L as compared to 316 mg/L for traditional Chardonnay) and in various
      individual polyphenols (catechin, epicatechin, procyanidins dimers B1-B4, gallic
      acid, cafeic acid, and caftaric acid), as determined from HPLC coupled to a diode
      array detector. The polyphenols-enriched white wine (W) or its ethanol-free
      derivative (EFW) was then administered by gavage (10 mL/kg, twice a day) for 6
      weeks to rats that have been rendered diabetic by a single iv injection of
      streptozotocin (55 mg/kg). Treatments had no effect on the symptoms associated
      with hyperglycemia. However, while a reduction in plasma antioxidant capacity was
      associated with the diabetic state, administration of W or EFW restored plasma
      antioxidant capacities to a level not significantly different from that of
      nondiabetic control animals. In addition, the effect of both treatments was
      manifested by the enlargement of mesenteric arteries, as determined by
      quantitative histomorphometry. In summary, our study indicates that white wine,
      when enriched in polyphenols, is able to induce ethanol-independent in vivo
      effects in a model of insulin-deficient diabetes characterized by a major
      oxidative stress.

PMID- 12502427
TI  - Nutritional and physiological responses of young growing rats to diets containing
      raw cowpea seed meal, protein isolate (globulins), or starch.
AB  - The nutritional and physiological effects of raw cowpea (Vigna unguiculata (L)
      Walp.) seed meal, protein isolate (globulins), or starch on the metabolism of
      young growing rats have been evaluated in 14-day trials. Wet and dry weight gain,
      feed conversion efficiency, and lipid and protein accretion were significantly
      reduced as a result of inclusion of seed meal, globulins, or starch in the diet,
      with growth retardation being most marked with the seed meal. The proportional
      weights of the small intestine and pancreas were increased by meal diets, and
      serum cholesterol levels were slightly reduced. The globulins and raw starch also
      increased relative small intestine weights but had no effect on the pancreas or
      serum constituents. The effects of cowpeas on rats appeared to be due primarily
      to the combined actions of globulins, resistant starches, protease inhibitors,
      and possibly fiber and non-starch polysaccharides on intestinal and systemic
      metabolism.

PMID- 12502428
TI  - Immunochemical screening and liquid chromatographic-tandem mass spectrometric
      confirmation of drug residues in edible tissues of calves injected with a
      therapeutic dose of the synthetic glucocorticoids dexamethasone and flumethasone.
AB  - A field study was performed to assess the drug residue level in edible tissues
      after a therapeutic application of the synthetic glucocorticoids dexamethasone
      and flumethasone. Three diseased calves were injected intramuscularly with a
      commercial batch of dexamethasone esters and slaughtered 72 h after treatment.
      Another three calves were injected intramuscularly with an aqueous flumethasone
      preparation and slaughtered 24 h later. Residues of synthetic glucocorticoids in
      liver, muscle, kidney, and urine were assessed by competitive enzyme immunoassay.
      All dexamethasone concentrations exceeded the maximal residue level of 0.75
      microg/kg in muscle and kidney and 2 microg/kg in the liver. The presence of both
      dexamethasone and flumethasone in the liver was confirmed by liquid
      chromatography coupled to tandem mass spectrometry (LC-MS/MS). These results
      indicate that liver tissue provides a suitable matrix to monitor the presence of
      illegal residues of synthetic glucocorticoids in slaughtered animals.

PMID- 12502429
TI  - Method for analysis of tannic acid and its metabolites in biological samples:
      application to tannic acid metabolism in the rat.
AB  - A new analytical method for measuring tannic acid (TA) using tannase was
      developed and applied to the investigation of TA metabolism in the rat following
      oral administration at a dose of 1.0 g/kg. The proposed method for TA
      determination was based on the enzymatic hydrolysis of TA to gallic acid (GA) and
      subsequent determination by HPLC. TA metabolites were determined by HPLC. 4-O
      Methylgallic acid (4-OMGA), pyrogallol (PY), and resorcinol (RE) were detected in
      serum. TA was excreted into urine as GA (0.01%), 4-OMGA (0.10%), PY (0.24%), and
      RE (2.06%) and into feces as TA (62.74%), GA (0.19%), PY (0.02%), and RE (0.76%)
      within 54 h after oral administration. It was suggested that >60% of TA remained
      unchanged but that some was hydrolyzed to GA by tannase in the intestine and
      further metabolized to 4-OMGA, PY, and RE.

PMID- 12502430
TI  - Isoflavone, glyphosate, and aminomethylphosphonic acid levels in seeds of
      glyphosate-treated, glyphosate-resistant soybean.
AB  - The estrogenic isoflavones of soybeans and their glycosides are products of the
      shikimate pathway, the target pathway of glyphosate. This study tested the
      hypothesis that nonphytotoxic levels of glyphosate and other herbicides known to
      affect phenolic compound biosynthesis might influence levels of these
      nutraceutical compounds in glyphosate-resistant soybeans. The effects of
      glyphosate and other herbicides were determined on estrogenic isoflavones and
      shikimate in glyphosate-resistant soybeans from identical experiments conducted
      on different cultivars in Mississippi and Missouri. Four commonly used herbicide
      treatments were compared to a hand-weeded control. The herbicide treatments were
      (1) glyphosate at 1260 g/ha at 3 weeks after planting (WAP), followed by
      glyphosate at 840 g/ha at 6 WAP; (2) sulfentrazone at 168 g/ha plus chlorimuron
      at 34 g/ha applied preemergence (PRE), followed by glyphosate at 1260 g/ha at 6
      WAP; (3) sulfentrazone at 168 g/ha plus chlorimuron at 34 g/ha applied PRE,
      followed by glyphosate at 1260 g/ha at full bloom; and (4) sulfentrazone at 168
      g/ha plus chlorimuron at 34 g/ha applied PRE, followed by acifluorfen at 280 g/ha
      plus bentazon at 560 g/ha plus clethodim at 140 g/ha at 6 WAP. Soybeans were
      harvested at maturity, and seeds were analyzed for daidzein, daidzin, genistein,
      genistin, glycitin, glycitein, shikimate, glyphosate, and the glyphosate
      degradation product, aminomethylphosphonic acid (AMPA). There were no remarkable
      effects of any treatment on the contents of any of the biosynthetic compounds in
      soybean seed from either test site, indicating that early and later season
      applications of glyphosate have no effects on phytoestrogen levels in glyphosate
      resistant soybeans. Glyphosate and AMPA residues were higher in seeds from
      treatment 3 than from the other two treatments in which glyphosate was used
      earlier. Intermediate levels were found in treatments 1 and 2. Low levels of
      glyphosate and AMPA were found in treatment 4 and a hand-weeded control,
      apparently due to herbicide drift.

PMID- 12502431
TI  - Polio eradication initiative in Africa: influence on other infectious disease
      surveillance development.
AB  - BACKGROUND: The World Health Organization (WHO) and partners are collaborating to
      eradicate poliomyelitis. To monitor progress, countries perform surveillance for
      acute flaccid paralysis (AFP). The WHO African Regional Office (WHO-AFRO) and the
      U.S Centers for Disease Control and Prevention are also involved in strengthening
      infectious disease surveillance and response in Africa. We assessed whether polio
      eradication initiative resources are used in the surveillance for and response to
      other infectious diseases in Africa. METHODS: During October 1999-March 2000, we
      developed and administered a survey questionnaire to at least one key informant
      from the 38 countries that regularly report on polio activities to WHO. The key
      informants included WHO-AFRO staff assigned to the countries and Ministry of
      Health personnel. RESULTS: We obtained responses from 32 (84%) of the 38
      countries. Thirty-one (97%) of the 32 countries had designated surveillance
      officers for AFP surveillance, and 25 (78%) used the AFP resources for the
      surveillance and response to other infectious diseases. In 28 (87%) countries,
      AFP program staff combined detection for AFP and other infectious diseases.
      Fourteen countries (44%) had used the AFP laboratory specimen transportation
      system to transport specimens to confirm other infectious disease outbreaks. The
      majority of the countries that performed AFP surveillance adequately (i.e., non
      polio AFP rate = 1/100,000 children aged <15 years) in 1999 had added 1-5
      diseases to their AFP surveillance program. CONCLUSIONS: Despite concerns
      regarding the targeted nature of AFP surveillance, it is partially integrated
      into existing surveillance and response systems in multiple African countries.
      Resources provided for polio eradication should be used to improve surveillance
      for and response to other priority infectious diseases in Africa.

PMID- 12502432
TI  - Global and regional estimates of cancer mortality and incidence by site: II.
      Results for the global burden of disease 2000.
AB  - BACKGROUND: Mortality estimates alone are not sufficient to understand the true
      magnitude of cancer burden. We present the detailed estimates of mortality and
      incidence by site as the basis for the future estimation of cancer burden for the
      Global Burden of Disease 2000 study. METHODS: Age- and sex- specific mortality
      envelope for all malignancies by region was derived from the analysis of country
      life-tables and cause of death. We estimated the site-specific cancer mortality
      distributions from vital records and cancer survival model. The regional cancer
      mortality by site is estimated by disaggregating the regional cancer mortality
      envelope based on the mortality distribution. Estimated incidence-to-mortality
      rate ratios were used to back calculate the final cancer incidence estimates by
      site. RESULTS: In 2000, cancer accounted for over 7 million deaths (13% of total
      mortality) and there were more than 10 million new cancer cases world wide in
      2000. More than 60% of cancer deaths and approximately half of new cases occurred
      in developing regions. Lung cancer was the most common cancers in the world,
      followed by cancers of stomach, liver, colon and rectum, and breast. There was a
      significant variations in the distribution of site-specific cancer mortality and
      incidence by region. CONCLUSIONS: Despite a regional variation, the most common
      cancers are potentially preventable. Cancer burden estimation by taking into
      account both mortality and morbidity is an essential step to set research
      priorities and policy formulation. Also it can used for setting priorities when
      combined with data on costs of interventions against cancers.

PMID- 12502433
TI  - Global and regional estimates of cancer mortality and incidence by site: I.
      Application of regional cancer survival model to estimate cancer mortality
      distribution by site.
AB  - BACKGROUND: The Global Burden of Disease 2000 (GBD 2000) study starts from an
      analysis of the overall mortality envelope in order to ensure that the cause
      specific estimates add to the total all cause mortality by age and sex. For
      regions where information on the distribution of cancer deaths is not available,
      a site-specific survival model was developed to estimate the distribution of
      cancer deaths by site. METHODS: An age-period-cohort model of cancer survival was
      developed based on data from the Surveillance, Epidemiology, and End Results
      (SEER). The model was further adjusted for the level of economic development in
      each region. Combined with the available incidence data, cancer death
      distributions were estimated and the model estimates were validated against vital
      registration data from regions other than the United States. RESULTS: Comparison
      with cancer mortality distribution from vital registration confirmed the validity
      of this approach. The model also yielded the cancer mortality distribution which
      is consistent with the estimates based on regional cancer registries. There was a
      significant variation in relative interval survival across regions, in particular
      for cancers of bladder, breast, melanoma of the skin, prostate and haematological
      malignancies. Moderate variations were observed among cancers of colon, rectum,
      and uterus. Cancers with very poor prognosis such as liver, lung, and pancreas
      cancers showed very small variations across the regions. CONCLUSIONS: The
      survival model presented here offers a new approach to the calculation of the
      distribution of deaths for areas where mortality data are either scarce or
      unavailable.

PMID- 12502434
TI  - [Indication, contraindication, and therapeutic evaluation of artificial liver
      support system].

PMID- 12502435
TI  - [The difficulty and prospect of gene therapy for hepatocyte carcinoma].

PMID- 12502436
TI  - [Current status of immuno-gene therapy for hepatocellular carcinoma].

PMID- 12502438
TI  - [Antitumor immunity elicited by 4-1BBL gene transfected Hepa1-6 in vivo].
AB  - OBJECTIVE: To study the effects of 4-1BBL on antitumor immunity induced in vivo
      by murine 4-1BBL gene transfected Hepa1-6. METHODS: Retrovirus vector was used to
      transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line
      Hepa1-6. The products were termed as Hepa1-6/4-1BBL, and then the TCV4-1BBL was
      obtained by treating them with mitomycin (MMC). Three models (immunological
      model, early model, and later model) were established to study the antitumor
      effects of TCV4-1BBL. RESULTS: (1)In immunological models, the syngeneic mice
      were completely protected by inoculation with TCV4-1BBL, survived free from tumor
      for a long period (over 100 days). (2)In early models (7 days after inoculation),
      Hepa1-6 tumor cells showed strong immunogenicity effects and (3) In later models
      (14 days after inoculation), they had obvious antitumor effects and most of the
      tumors were disappeared. CONCLUSIONS: The antitumor effect against syngeneic
      murine hepatocellular carcinoma in vivo is obviously enhanced by treating them
      with TCV4-1BBL

PMID- 12502439
TI  - [Study on the effects of combined IL-12 and GM-CSF gene therapy for murine liver
      cancer].
AB  - OBJECTIVE: To study the anti-tumor effects of combined IL-12 and granalocyte
      macrophage-colong scimulating factor (GM-CSF) gene therapy on murine
      hepatocellular carcinoma. METHODS: Twenty-four mice received subcutaneous
      inoculation of 1 x 10(6) BNL hepatoma cells were randomly divided into the
      following four groups with different cytokine encoding plasmids (6 mice for each
      group): (1)pXX-GM-CSF 12.5 microg and pXX-IL-12 12.5 microg; (2)pXX-IL-12 25
      microg; (3)pXX-GM-CSF 25 microg; (4)pXX-Neo 25 microg. The plasmids were given
      through tail vein using a versatile hydrodynamics-based DNA delivery method on
      day 3 and day 6 after tumor challenge. The growth of tumor and cellular immune
      response were observed intensively. The changes in serum concentration of IL-12,
      GM-CSF, and IFN-gamma after plasmids injection were also observed. RESULTS: Co
      delivery of IL-12 and GM-CSF could mount stronger anti-tumor effects, longer term
      enhanced IL-12 expression and lower level of IFN-gamma than did IL-12 alone.
      CONCLUSIONS: Combined IL-12 and GM-CSF can render a strong anti-tumor effect as
      well as a potential to lower the side effects.

PMID- 12502440
TI  - [Immunoprotective effect of IL-2 and B7-1 gene co-transfected liver cancer
      vaccines on hepatocarcinogenesis in mice].
AB  - OBJECTIVE: To study the immunoprotective effect of IL-2 and B7-1 gene co
      transfected liver cancer vaccine on hepatocarcinogenesis in mice. METHODS: The
      murine liver cancer cell strain Hepal-6 was transfected with IL-2 and/or B7-1
      gene via recombinant adenovirus vectors and the liver cancer vaccines were
      prepared. C57BL/6 mice were immunized with the vaccines and challenged with the
      parental Hepal-6 cells afterwards. The immunoprotection was investigated and the
      reactive T cell line was assayed. RESULTS: The effect of the Hep6-IL2/B7 vaccine
      on the onset of tumor formation was the strongest. The media survival time of the
      mice was the longest (68 days, P<0.05) and the implanted tumor was the smallest
      (P<0.05). The effect of single IL-2 or B7-1 gene-transfected vaccine was next to
      the co-transfected gene group with the mean survival time being 59 and 54 days,
      respectively. The mean survival time of wild or BGFP gene modified vaccine
      immunized group was 51 and 48 days, respectively. The control group all died
      within 38 days and the implanted tumor was the largest (P<0.05). The cellular
      immunofunction test and cytotoxicity study showed that the mice immunized with
      the Hep6-IL2/B7 vaccine gained significantly increased NK, LAK and CTL activity
      (29.0% +/- 2.5%, 65.0% +/- 2.9%, 83.1% +/- 1.5% respectively, compared with other
      groups P<0.05). CONCLUSIONS: The IL-2 and B7-1 gene co-transfected liver cancer
      vaccines can induce the mice to produce activated and specific CTL against the
      parental tumor cells, and demonstrate stronger effect on the hepatocarcinogenesis
      than single gene modified or the regular tumor vaccine. Therefore, the vaccines
      may become a novel potential therapy for recurrence and metastases of HCC.

PMID- 12502441
TI  - [Injection of NKG5SV gene to inhibit growth and metastasis of hepatocellular
      carcinoma].
AB  - OBJECTIVE: To study the injection of NKG5SV gene to inhibit growth and metastasis
      of hepatocellular carcinoma (HCC). METHODS: NKG5SV gene was inserted into
      retroviral vector pLXSN by normal methods. LacZ gene was used as control. LCI-D20
      tumor together with saline, pLXSN-LacZ DNA or pLXSN-NKG5SV was subcutaneously
      inoculated to the nude mice. Tumor formation rate and tumor size were noted 35
      days after inoculation. LCI-D20 tumor was inoculated subcutaneously. Saline,
      pLXSN-LacZ DNA or pLXSN-NKG5SV was intratumorally injected respectively 10 days
      after inoculation. Tumor growth was observed 35 days after inoculation. Liver
      cancer was resected 22 days after intrahepatic inoculation. Saline, pLXSN-LacZ
      DNA or pLXSN-NKG5SV was respectively injected at incisal margin or intraspleen.
      Mice were killed 35 days after inoculation to observe tumor recurrence at incisal
      margin, intrahepatic metastasis and extrahepatic metastasis. RESULTS: Tumor
      formation rate and tumor diameter(cm) were 1.76 +/- 0.11, 1.51 +/- 0.34, 0.33 +/-
      0.04 in the control group, LacZ group, NKG5SV group respectively when tumor and
      different cDNA were inoculated together. Tumor diameter(cm) and weight(g) were
      0.87 +/- 0.08, 0.83 +/- 0.05, 0.26 +/- 0.04; 0.43 +/- 0.06, 0.38 +/- 0.04, 0.08
      +/- 0.06 in the control group, LacZ group, NKG5SV group respectively when
      different cDNA were injected into the LCI-D20 tumor. Sites with extrahepatic
      metastasis nidi, incisal margin recurrence tumor size(cm), intrahepatic
      metastasis nidi, metastasis involved hepatic lobes in the control group, LacZ
      group, NKG5SV group were 4.25 +/- 1.48, 4.25 +/- 1.04, 0.63 +/- 0.51; 1.51 +/-
      0.27, 1.35 +/- 0.17, 0.81 +/- 0.17; 2.50 +/- 1.41, 2.38 +/- 1.06, 1.25 +/- 0.71;
      2.13 +/- 0.99, 2.00 +/- 0.75, 1.38 +/- 0.74 respectively when NK cells were
      injected at incise margin. They were 4.38 +/- 1.85, 4.25 +/- 1.48, 1.00 +/- 0.75;
      1.13 +/- 0.23, 0.97 +/- 0.29, 0.76 +/- 0.16; 2.50 +/- 1.41, 2.05 +/- 1.12, 0;
      2.13 +/- 0.83, 1.75 +/- 0.88, 0 respectively when NK cell were injected
      intrasplenicly. CONCLUSIONS: NKG5SV gene can inhibit HCC growth and postoperative
      metastasis and recurrence.

PMID- 12502442
TI  - [One case analysis of adult type Niemann-Pick disease].

PMID- 12502443
TI  - [Effects of polypeptides from HCV core region on the function of cytotoxic T
      cells].
AB  - OBJECTIVE: To investigate the pathogenesis of cytotoxic T cell (CTL) dysfunction
      in patients with HCV infection. METHODS: BALB/c mice were immunized by
      subcutaneous injection of polypeptides from HCV core region, and the CTL activity
      of mouse spleen cells was detected by the LDH release test. Two polypeptides
      which can enhance CTL function and two polypeptides which can inhibit CTL
      function were selected and cross-combined. BALB/c mice were immunized using the
      combined polypeptides and the CTL activities were detected afterwards. RESULTS:
      CTL activity was inhibited by CPA9 (39-74 amino acids), CPB7 (67-76 amino acids)
      and CPB8 (71-80 amino acids), and promoted by CPA10 (5-23 amino acids), CPB6 (63
      72 amino acids) and CPB2 (131-140 amino acids). Using single factor analysis of
      variance, the CTL activity in the mice could be enhanced by polypeptides from the
      HCV core region, CPB2+CPB8, CPB6+CPB8, respectively. There was no obvious
      difference between CPB2+CPB7, CPB6+CPB7 and negative control. CONCLUSIONS: CPA9,
      CPB7, and CPB8, the 3 polypeptides from HCV core region play an inhibition role
      and CPA10, CPB6, and CPB2 play an enhancement role in CTL activity in mice. The
      inhibition and enhancement functions of the polypeptides from HCV core region
      interact each other.

PMID- 12502444
TI  - [Establishment and evaluation of the method for detecting HBV DNA in serum using
      HBV DNA probe labeled directly by alkaline phosphatase].
AB  - OBJECTIVE: To establish a sensitive and specific technique for detecting HBV DNA
      in serum using HBV DNA probe labeled directly by alkaline phosphatase (AlkPhos
      Direc probe). METHODS: The probe that purified HBV DNA sequence was labeled
      directly by alkaline phosphatase and chemiluminescent substrate CDP-star for AP
      was used in the hybridization assay. HBV DNA was detected by autoradiography on
      the film. The test compared the chemiluminescen dot blot hybridization assay for
      80 samples with digoxigenin-labeled HBV DNA probe detective method. The
      correlation of 70 samples test results between fluorescent quantitative HBV DNA
      PCR method and dot blot hybridization assay by AlkPhos Direc probe was analysed.
      RESULTS: The sensitivity of the probe labeled directly by alkaline phosphatase
      was 10pg at least. The coincidence was 100% compared with digoxigenin-labeled HBV
      DNA probe detection. A correlation coefficient of HBV DNA quantitative results
      between fluorescent quantitative HBV DNA PCR (QPCR) method and dot blot
      hybridization assay by AlkPhos Direc probe was 0.98 (P<0.01). CONCLUSIONS: The
      method detecting HBV DNA in serum by HBV DNA AlkPhos Direc probe is sensitive and
      specific. The results between two methods with AlkPhos Direc and digoxigenin
      labeled HBV DNA probe are coincident completely. The correlation of HBV DNA
      quantitative results between fluorescent QPCR method and dot blot hybridization
      assay by AlkPhos Direc probe is satisfactory.

PMID- 12502445
TI  - [The level of IL-8 in the serum of patients suffering from chronic hepatic
      diseases and primary hepatocellular carcinoma].
AB  - OBJECTIVE: To explore the relation between the pathogenesis and IL-8 level in the
      chronic hepatic disease and primary hepatocellular carcinoma. METHODS: 5ml venous
      blood was with drawn from 80 hospitaliged patients with different types of
      hepatic diseases and 14 healthy people. The serum was separated from the blood
      and then kept at -40 degrees Centigrade, and finally detected for IL-8 by ELISA.
      RESULTS: There was an obvious difference among the IL-8 level in the serum from
      different types of hepatic disease patients. The IL-8 level was 75.80 microg/L
      33.39 microg/L in chronic virus hepatitis and it was 89.54 microg/L 13.24
      microg/L for primary hepatoma patients (t=10.48 and 4.01, respectively, P<0.01,
      as compared with control group). CONCLUSIONS: There is a close relation between
      the level of IL-8 in serum and the state of illness. For patients with chronic
      hepatic diseases and primary hepatocellular carcinoma, the higher the IL-8 level
      is, the more serious the patients' condition, the worse the prognosis, and the
      higher the death rate would be.

PMID- 12502446
TI  - [Clinical and histological features of fibrosing cholestatic hepatitis].
AB  - OBJECTIVE: To investigate the clinical and histological characteristics of
      fibrosing cholestatic hepatitis (FCH) and the therapeutic effect of lamivudine.
      METHODS: By retrospective analysis, 17 cases developed severe jaundice in 794
      renal-transplanted recipients, and of them, FCH was clinically suggested in 11
      and confirmed by liver biopsy in 6 cases. RESULTS: The prevalence of chronic HBV
      infection in renal transplantation patients was 9.3%, of whom the FCH occurred in
      22.9%. In 6 liver-biopsied cases, the onset was within 1.5-22 months. Two cases
      remitted who had early received lamivudine and 4 cases who were treated with the
      drug before transplantation did not develop the disease. All patients received
      large amounts of multiple immuno-suppressors after transplantation. About one
      fifth of HBV-infected cases gradually developed cholestatic hepatitis and some of
      them rapidly proceeded to hepatic failure. All had very high serum level of HBV
      DNA. The histology revealed unique lesion combination. The hepatocytes had
      widespread ballooning change and some ground-glass appearance. There were liver
      cytolysis and focal cell loss, bile stasis, periportal fibrosis, while only mild
      lymphocytic infiltration. CONCLUSIONS: Fibrosing cholestatic hepatitis may happen
      following renal transplantation. Lamivudine has marked therapeutic effect for
      FCH.

PMID- 12502447
TI  - [Portosystemic shunt via the left branch of portal vein for the prevention of
      encephalopathy following transjugular intrahepatic portosystemic shunt].
AB  - OBJECTIVE: To determine and analyze plasma ammonia concentration difference of
      the portal vein system and ramifications of rabbits and consequently guide
      selection of the portal vein in transjugular intrahepatic portosystemic shunt
      (TIPS) so that reduce shunt-induced hepatic encephalopathic incidence. To
      evaluate clinical significance of transjugular intrahepatic left branch of portal
      vein portosystemic shunt (TILPS) and to analyse hemodynamics of both branches of
      the portal vein and to observe long-term results in the prevention of
      encephalopathy. METHODS: Blood samples in different portal vein branches of
      rabbits were collected and the plasma ammonia concentration was assayed and
      compared. The left branch of portal vein was used as the puncture site to perform
      TILPS and to keep away from the right branch of portal vein blood that contains
      nutrition and toxin. RESULTS: Plasma ammonia content was superior in the
      mesenteric vein and higher than the portal vein branch, the splenic vein, and the
      vena cava. The right portal vein was above the left. Encephalopathy did not occur
      in all patients within 3 months. Of the 341 patients undergoing TILPS,
      encephalopathy occurred in only 5 patients (1.47%) and shunt abnormalities in 19
      patients (5.57%) verified by venography during overall follow-up period.
      CONCLUSIONS: Selective left branch of the portal vein portosystemic shunt can
      decrease encephalopathy obviously and protect liver function.

PMID- 12502448
TI  - [Role of hepatic sinusoidal endothelium injury in hepatic fibrogenesis induced by
      dimethylnitrosamine in rats].
AB  - OBJECTIVE: To study the role of hepatic sinusoidal endothelium injury during
      hepatic fibrogenesis induced by dimethylnitrosamine (DMN) in rats. METHODS:
      Hepatic fibrosis of rats was induced by administration of DMN intraperitoneally
      three times a week for 4 weeks. The animals were harvested on day 2 and week 1,
      2, 3, 4, 5, 6, 8, 12, and 24. The formation of liver fibrosis and hepatic
      sinusoid capillarization were successively observed by morphological observation
      and other methods. RESULTS: Two days after treated with DMN, there was no obvious
      changes in the liver, but the fenestration of the sinusoidal endothelial cells
      decreased, and it became more obvious after one week. After four weeks, there was
      a large necrotic area and a number of pseudolobes appeared. The HA in the serum
      was lower than that of control (231.30 ng/ml +/- 143.80 ng/ml vs 56.50 ng/ml +/-
      18.10 ng/ml; t=3.14, P<0.05), but the hydroxyproline content was obviously higher
      than that of control (223.04 microg/g +/- 37.09 microg/g vs 61.55 microg/g +/-
      20.85 microg/g; t=8.28, P<0.05). Hepatic sinusoid capillarization was gradually
      formed and defenestration of the hepatic sinusoidal endothelium preceded the
      appearance of serious hepatocellular damage, hepatic fibrosis and basement
      membrane. CONCLUSIONS: The damage and phenotypic alteration of the hepatic
      sinusoidal endothelium may be a vital issue triggering the liver fibrosis induced
      by DMN.

PMID- 12502449
TI  - [Establishment and identification of the gene cell line transfected aldose
      reductase like gene and its drug resistance to drugs containing carbonyl group].
AB  - OBJECTIVE: To investigate the relationship between aldose reductase like protein
      (ARL-1) gene overexpressed in HCC cells and drug-resistance of the cell to drugs
      containing carbonyl group. METHODS: To establish ARL-1 stable expression positive
      cell line, eukaryotic expression vectors containing ARL-1 gene cDNA were
      transfected into Hep cell mediated by lipofect AMINE. The positive monoclones
      were determined by PCR and RT-PCR, respectively. Then MTT assay was used to study
      the drug resistance ability of the cells to drugs containing carbonyl after
      incubating three days with those drugs. RESULTS: After ARL-1 gene transfection
      mediated by lipofect AMINE, one positive monoclonal cell overexpressing ARL-1
      gene was selected. Compared with the control cell group, drug resistance ability
      of the positive cells to ADM and MMC which contain carbonyl group increased 2.3
      and 3.17 fold, respectively (t=6.39, P=0.016 in ADM group and t=30.06, P=0.001 in
      MMC group). In the same time, drug resistance ability to 5-FU which has no
      carbonyl group had no statistical difference between positive monoclonal cell
      group and control cell group (t=0.684, P=0.531). CONCLUSIONS: The Hep ARL-1
      positive cell line with stable expression of ARL-1 gene has been established
      successfully and the up-regulation of ARL-1 gene may plays an important role in
      drug resistance of the cells to anticancer drugs containing carbonyl group.

PMID- 12502450
TI  - [Effects of curcumin on proliferation and apoptosis in human hepatic cells].
AB  - OBJECTIVE: To investigate the effect of curcumin on the proliferation, cell cycle
      distribution and apoptosis of hepatocarcinoma cell line QGY. METHODS: The MTT
      method was used to assay the biologic activities of curcumin in different times
      and different doses. The cell cycle distribution was detected by flow cytometic
      analysis. The cell ultrastructure was observed by electronic microscopy. RESULTS:
      Curcumin could inhibit effectively QGY in a dose- and time- dependent manner.
      IC(50) of curcumin to QGY was 49.50 micromol/L in 72 hours. The cell growth was
      arrested at S stage. Curcumin could lead to the degeneration, necrosis, and
      apoptosis. CONCLUSIONS: Curcumin can interrupt the cell cycle and has a role in
      cytotoxicity, antiproliferation and inducing apoptosis of QGY.

PMID- 12502451
TI  - [Interventional therapy combining Seed of Job's-stears with lipiodol for hepatoma
      bearing rats].
AB  - OBJECTIVE: To study the effect of the interventional therapy of hepatoma-bearing
      rat by Seed of Job's-stears (SJS) injection combining with lipiodol. METHODS: To
      evaluate the effect of SJS as a medicament which can be used in interventional
      therapy, we repeated the hepatoma-bearing rats, and treated them by
      interventional therapy with SJS referring to the method which Lindel set up,
      comparing its effect to which of chemical medicines and lipiodol. RESULTS: SJS or
      lipiodol alone had an inhibiting effect to liver cancer. The tumor growth rates
      were 13.89%, 14.05%, and the tumor inhibiting rates reached 38.10%, 37.49%. The
      curative effect of the SJS/lipiodol group was the best, and its growth rate and
      inhibiting rate were 3.36% and 85.03%, respectively better than the SJS group and
      lipiodol group (P<0.01). There was no statistically significant difference
      between the effect of the SJS/lipiodol group and the mitomycin/lipiodol group.
      The survival period of SJS/lipiodol group was longer than the rest groups (P<0.01
      or P<0.05). CONCLUSIONS: The interventional therapy by SJS/lipiodol has obvious
      inhibitory effect on the growth of hepatoma-bearing rats, which is similar to
      that of MMC/lipiodol. This inhibiting effect is better than that of the SJS or
      lipiodol group. SJS/lipiodol can prolong the survival period of hepatoma-bearing
      rats obviously, and this effect is better than that of single lipiodol, SJS or
      MMC/lipiodol.

PMID- 12502452
TI  - [Whether the impairment of grafted liver was induced by the inflammatory cells in
      cold and warm ischemia after transplantation].
AB  - OBJECTIVE: To investigate whether the impairment of grafted liver after
      transplantation was induced by the same inflammatory cells in cold and warm
      ischemia. METHODS: Male SD rats were divided into two groups randomly, 24 grafted
      livers in each group were stored for 120 or 240 min at 4 degrees Centigrade
      Ringer's solution. Also male SD rats were divided into three groups, in which 24
      grafted livers in each group were experienced warm ischemia ranged from 90, 120
      to 150 min from non-heart-beating donor. The recipients were killed after 1, 3,
      6, and 24 hours of transplantation for sample collection. RESULTS: Along with the
      prolongation of cold and warm ischemia time, the serum ALT and AST levels were
      increased gradually after transplantation. Light microscopy showed some necroses
      in hepatocytes after 3 and 6 hours of transplantation in cold ischemia, and some
      neutrophilic infiltration in sinusoids. There were a large number of hepatocytes
      necroses after 3, 6 hours of transplantation in warm ischemia from non-heart
      beating donor and a lot of lymphocytic infiltration in sinusoids. The findings in
      electron microscopy were as the same as those found in light microscopy, and the
      lymphocytes which infiltrated in sinusoids in warm ischemia were identified as T
      lymphocytes in electron microscopy. CONCLUSIONS: The impairment of grafted livers
      after transplantation seems to be induced by two different inflammatory cells in
      cold and warm ischemia, that is, neutrophils mediate the cold ischemia
      reperfusion, and T lymphocytes mediate the warm ischemia-reperfusion from non
      heart-beating donor.

PMID- 12502453
TI  - [Liver biopsy complicated by vaso-vagal episodes].

PMID- 12502454
TI  - [Influence of hepatotropic virus-infection in patients with chronic hepatitis B
      on the level of HBV DNA and state of illness].

PMID- 12502455
TI  - [The value of thoracoscopy for diagnosis and management of refractory hepatic
      hydrothorax].

PMID- 12502456
TI  - [Affection of chronic ethanol toxicosis on cytokine expression].

PMID- 12502457
TI  - [Establishment of a cisplatin-induced resistant human hepatocellular carcinoma
      cell model and preliminary study on its resistant mechanisms].

PMID- 12502458
TI  - [The model's establishment of the single cell (HepG2) clones over expressed ARL-1
      gene].

PMID- 12502459
TI  - [Epidemiology of alcohol and liver disease].

PMID- 12502460
TI  - [Development of lamivudine-resistance microarray and its reliability in clinical
      examination].

PMID- 12502461
TI  - [Sequential variation in 3' untranslated region of hepatitis C virus in mainland
      of China].

PMID- 12502462
TI  - [Researching progress on prognosis judgment of hepatic failure].

PMID- 12502463
TI  - [Endotoxin and cytokines change in alcoholic liver disease].

PMID- 12502464
TI  - [The progress of study on hepatogenic diabetes].

PMID- 12502465
TI  - [Misdiagnosis of 3 adult liver hamartomas].

PMID- 12502466
TI  - [Receptors of hepatic stellate cells: new insights and prospects for therapy].

PMID- 12502467
TI  - Bronchopulmonary dysplasia: one disease or two?

PMID- 12502468
TI  - Tethering tracheobronchial airways within the lungs.

PMID- 12502469
TI  - Is chronic obstructive pulmonary disease related to sleep apnea-hypopnea
      syndrome?

PMID- 12502470
TI  - Education theory applied to critical care: Dewey versus tradition: it really does
      matter.

PMID- 12502471
TI  - Do complex conditions require complex treatment?

PMID- 12502472
TI  - Sleep and sleep-disordered breathing in adults with predominantly mild
      obstructive airway disease.
AB  - Neither the association between obstructive airways disease (OAD) and sleep apnea
      hypopnea (SAH) nor the sleep consequences of each disorder alone and together
      have been characterized in an adult community setting. Our primary aims were (1)
      to determine if there is an association between OAD and SAH and (2) identify
      predictors of oxyhemoglobin desaturation during sleep in persons having OAD with
      and without SAH. Polysomnography and spirometry results from 5,954 participants
      in the Sleep Heart Health Study were analyzed. OAD was defined by a FEV1/FVC
      value less than 70%. Assessment of SAH prevalence in OAD was performed using
      thresholds of respiratory disturbance index (RDI) greater than 10 and greater
      than 15. A total of 1,132 participants had OAD that was predominantly mild
      (FEV1/FVC 63.81 +/- 6.56%, mean +/- SD). SAH was not more prevalent in
      participants with OAD than in those without OAD (22.32 versus 28.86%, with and
      without OAD, respectively, at RDI threshold values greater than 10; and 13.97
      versus 18.63%, with and without OAD, respectively, at RDI threshold value greater
      than 15). In the absence of SAH, the adjusted odds ratio for sleep desaturation
      (> 5% total sleep time with saturation < 90%) was greater than 1.9 when FEV1/FVC
      was less than 65%. Participants with both OAD and SAH had greater sleep
      perturbation and desaturation than those with one disorder. Generally mild OAD
      alone was associated with minimally altered sleep quality. We conclude that (1)
      there is no association between generally mild OAD and SAH; (2) exclusive of SAH
      and after adjusting for demographic factors and awake oxyhemoglobin saturation,
      an FEV1/FVC value less than 65% is associated with increased risk of sleep
      desaturation; (3) desaturation is greater in persons with both OAD and SAH
      compared with each of these alone; and (4) individuals with generally mild OAD
      and without SAH in the community have minimally perturbed sleep.

PMID- 12502473
TI  - A randomized trial of laser-assisted uvulopalatoplasty in the treatment of mild
      obstructive sleep apnea.
AB  - Laser-assisted uvulopalatoplasty (LAUP) is an outpatient surgical treatment for
      snoring and obstructive sleep apnea (OSA), but to date, no controlled trials have
      been published. Forty-five subjects with mild OSA (apnea/hypopnea index [AHI], 10
      27 per hour) were randomized to LAUP or to no treatment (control group). The AHI
      post-LAUP was reduced by 21% overall and to 10 or less per hour in 5 of 21
      subjects (24%). Four of 24 subjects in the control group (16.7%) had an AHI of 10
      or less per hour at outcome. The AHI decreased with the LAUP compared with no
      change with the control group at outcome. Ten subjects (48%) reported
      significantly improved snoring after the LAUP. There was no improvement in
      excessive daytime sleepiness, but there was a small improvement in quality of
      life (unless side effects were included in the quality of life score). Side
      effects were common, but serious complications did not occur. LAUP surgery is
      effective in some subjects with mild OSA for the treatment of snoring, but the
      reduction in AHI and the level of symptomatic improvement were minor overall.

PMID- 12502474
TI  - Cost-effectiveness analysis of diagnostic strategies for suspected pulmonary
      embolism including helical computed tomography.
AB  - We performed a formal decision analysis to evaluate the cost-effectiveness of
      various strategies for pulmonary embolism, including helical computed tomography
      (CT), and determined the most cost-effective schemes for each clinical
      probability of pulmonary embolism. Other tests included D-dimer (DD), lower limb
      venous ultrasound (US), ventilation-perfusion (V/Q) scan, and angiography.
      Outcome measures were 3-month survival and costs per patient managed. Baseline
      sensitivity of CT was 70%, corresponding to the performance of single-detector
      CT, and that figure was raised in sensitivity analysis to account for the
      expected higher sensitivity of newer multidetector CT scanners. All strategies
      were compared with a reference strategy, namely the V/Q scan in all patients
      followed when nondiagnostic by an angiogram. For low clinical probability
      patients, the most cost-effective strategy was DD, US, and V/Q scan, patients
      with a nondiagnostic V/Q scan being left untreated. Replacing V/Q scan by CT was
      also cost-effective. For intermediate and high clinical probability patients, a
      fourth test must be added, either CT or angiography in patients with
      nondiagnostic V/Q scan, or angiography in patients with a negative helical CT.
      When using sensitivity figures above 85% (in the multidetector range), DD, US,
      and CT became the most cost-effective strategy for all clinical probability
      categories. Helical CT as a single test was not cost-effective. In summary,
      including helical CT in diagnostic strategies for pulmonary embolism is cost
      effective provided that it is combined with DD and US. In contrast, helical CT as
      a single test is not cost-effective.

PMID- 12502475
TI  - Airway alveolar attachment points and exposure to cigarette smoke in utero.
AB  - The harmful effects of in utero cigarette smoke exposure include increased asthma
      symptoms and reduced lung function during the neonatal period, increased airway
      responsiveness to inhaled stimuli, and an increased risk of sudden infant death
      syndrome. Altered lung function may result from altered airway/lung structure.
      Airway dimensions, alveolar attachment points, and parenchymal elastin content
      were measured in 32 infants who died from sudden infant death syndrome and were
      grouped according to their perinatal cigarette smoke exposure. Compared with
      those without any exposure to cigarette smoke, the distance between alveolar
      attachments on airways was greater (p < 0.001) in infants exposed to cigarette
      smoke only in utero or both in utero and during the postnatal period but not
      different in those with only postnatal exposure. The percentage of elastin within
      the alveolar walls was similar in all the exposure groups. These findings suggest
      that in utero cigarette smoke exposure may result in abnormal airway function due
      to a reduction of the forces opposing airway narrowing.

PMID- 12502476
TI  - Differential regulation by glucocorticoid of interleukin-13-induced eosinophilia,
      hyperresponsiveness, and goblet cell hyperplasia in mouse airways.
AB  - Interleukin (IL)-13 induces important features of bronchial asthma such as
      eosinophilic infiltration, airway hyperresponsiveness (AHR), and mucus
      hypersecretion. Although glucocorticoids suppress airway inflammation and remain
      the most effective therapy for asthma, the effects of glucocorticoids on the IL
      13-dependent features are unknown. We studied the effects of dexamethasone on
      eotaxin production, eosinophil accumulation, goblet cell hyperplasia, and AHR
      after IL-13 administration into the airways of mice in vivo. MUC5AC gene
      expression, a marker of goblet cell hyperplasia, was also analyzed. IL-13 alone
      dose dependently induced AHR. Treatment with dexamethasone inhibited eotaxin
      expression and completely abolished eosinophil accumulation, but it did not
      affect AHR, MUC5AC overexpression, or goblet cell hyperplasia induced by IL-13.
      The effects of tumor necrosis factor-alpha on IL-13-induced AHR were also
      examined. Tumor necrosis factor-alpha did not affect AHR despite marked
      enhancement of eosinophil infiltration in IL-13-treated mice. These findings
      suggest that glucocorticoid is not sufficient to suppress IL-13-induced AHR or
      goblet cell hyperplasia and that eotaxin expression and eosinophilic inflammation
      do not have a causal relationship to the induction of AHR or goblet cell
      hyperplasia by IL-13. Control of steroid-resistant features induced by IL-13,
      including AHR and mucus production, may provide new therapeutic modalities for
      asthma.

PMID- 12502477
TI  - A catalytic antioxidant attenuates alveolar structural remodeling in
      bronchopulmonary dysplasia.
AB  - Superoxide anion and other oxygen-free radicals have been implicated in the
      pathogenesis of bronchopulmonary dysplasia. We tested the hypothesis that a
      catalytic antioxidant metalloporphyrin AEOL 10113 can protect against hyperoxia
      induced lung injury using a fetal baboon model of bronchopulmonary dysplasia.
      Fetal baboons were delivered by hysterotomy at 140 days of gestation (term = 185
      days) and given 100% oxygen for 10 days. Morphometric analysis of alveolar
      structure showed that fetal baboons on 100% oxygen alone had increased
      parenchymal mast cells and eosinophils, increased alveolar tissue volume and
      septal thickness, and decreased alveolar surface area compared with animals given
      oxygen as needed. Treatment with AEOL 10113 (continuous intravenous infusion)
      during 100% oxygen exposure partially reversed these oxygen-induced changes.
      Hyperoxia increased the number of neuroendocrine cells in the peripheral lung,
      which was preceded by increased levels of urine bombesin-like peptide at 48 hours
      of age. AEOL 10113 inhibited the hyperoxia-induced increases in urine bombesin
      like peptide and numbers of neuroendocrine cells. An increasing trend in
      oxygenation index over time was observed in the 100% oxygen group but not the
      mimetic-treated group. These results suggest that AEOL 10113 might reduce the
      risk of pulmonary oxygen toxicity in prematurely born infants.

PMID- 12502478
TI  - Expression of connective tissue growth factor in asthmatic airway smooth muscle
      cells.
AB  - There is strong evidence to implicate transforming growth factor-beta in the
      remodeling that occurs in asthma, as levels are increased in bronchial lavage
      fluid and gene expression is increased in bronchial tissue. Transforming growth
      factor-beta is also known to increase the release of collagen from airway smooth
      muscle. Here we identify for the first time a possible mechanism for the effects
      of transforming growth factor-beta. Transforming growth factor-beta specifically
      induces mRNA and protein for connective tissue growth factor in airway smooth
      muscle, and moreover, we report that the connective tissue growth factor response
      is greater in airway smooth muscle cultured from patients with asthma compared
      with patients without asthma. This occurs at both the level of mRNA (37.53 +/-
      11.62- and 13.59 +/- 3.12-fold increase at 24 hours compared with time 0,
      respectively, p < 0.02) and protein production (67.57 +/- 27.80- and 3.58 +/- 0.6
      fold increase at 24 hours compared with time 0, respectively, p < 0.03). The
      differential connective tissue growth factor response to transforming growth
      factor-beta in asthmatic airway smooth muscle identifies a potential role for
      connective tissue growth factor in the remodeling that is characteristic of
      severe persistent asthma.

PMID- 12502479
TI  - Early thickening of the reticular basement membrane in children with difficult
      asthma.
AB  - Remodeling of the airway wall occurs in adults with asthma, and reticular
      basement membrane (RBM) thickening is pathognomonic of the asthma process. To
      investigate whether RBM thickening is present in children with difficult asthma
      and comparable to that seen in adults with asthma, we used light microscopy to
      measure RBM thickness in plastic-embedded endobronchial biopsy sections from 19
      children with difficult asthma who were prescribed 1,600 microg/day or more of
      inhaled steroids (age range, 6-16 years), 10 children without asthma (7-16
      years), and three adult groups: 8 healthy control subjects (21-42 years), 10 mild
      steroid-naive subjects with asthma (18-41 years), and 6 adults (3 steroid naive
      and 3 on inhaled steroids) intubated after a life-threatening attack of asthma
      (20-64 years). RBM thickness in the children with asthma was similar to that in
      adults with either mild or life-threatening asthma (median 8.2 [range 5.4-11.1]
      versus 8.1 [5.8-10.0] and 7.2 [2.8-10.0] microm, respectively) and greater than
      either adult or pediatric control subjects (8.2 [5.4-11.1] versus 4.4 [3.2-6.3]
      microm, p < 0.01, and 4.9 [3.7-8.3] microm, p < 0.01). We conclude that RBM
      thickening is already present in children with difficult asthma and to a similar
      extent to that seen in adults with asthma. In addition, we find no association
      with age, symptom duration, lung function, or concurrent eosinophilic airway
      inflammation.

PMID- 12502480
TI  - Localization of insulin-like growth factor-I in lung tissues of patients with
      fibroproliferative acute respiratory distress syndrome.
AB  - Insulin-like growth factor-I (IGF-I) is elevated in human fibrotic lung diseases
      and in animal models of pulmonary fibrosis, implicating IGF-I in the pathogenesis
      of fibrotic lung disease. We questioned whether IGF-I protein levels were
      enhanced in fibroproliferative acute respiratory distress syndrome (FP-ARDS).
      Serial lung tissue sections from a biopsy database were immunohistochemically
      stained for IGF-I, IGF-I receptor, CD68, alpha-smooth muscle actin, collagens I
      and III, and proliferating cell nuclear antigen. Our results show enhanced
      staining of IGF-I and IGF-I receptor, collagens I and III, smooth muscle actin,
      CD68, and proliferating cell nuclear antigen in FP-ARDS compared with control
      lung sections. In FP-ARDS specimens, prominent staining of IGF-I and IGF-I
      receptor was seen in alveolar and interstitial macrophages as well as in a
      variety of mesenchymal cells. There was a correlation between IGF-I staining and
      CD68-positive cells, suggesting macrophages as a potential source of the IGF-I
      protein present in lungs. IGF-I also correlated with enhanced collagen I,
      collagen III, and proliferating cell nuclear antigen immunoreactivity, suggesting
      that IGF-I may play a role in the extracellular matrix protein deposition and
      cellular proliferation seen in the lungs of individuals with FP-ARDS. Our results
      indicate that IGF-I is increased in FP-ARDS and may be an important mediator in
      the progression of acute lung injury to FP-ARDS.

PMID- 12502482
TI  - Do low exhaled condensate NH4+ concentrations in asthma reflect reduced pulmonary
      production?

PMID- 12502483
TI  - Recruitment maneuvers during lung protective ventilation in acute respiratory
      distress syndrome.

PMID- 12502484
TI  - Serum levels of vascular endothelial growth factor are elevated in patients with
      obstructive sleep apnea and severe night time hypoxia.

PMID- 12502485
TI  - Continuous positive airway pressure normalizes pulmonary artery pressures in
      subjects with obstructive sleep apnea and pulmonary hypertension.

PMID- 12502486
TI  - Are oxidative stress-activated signaling pathways mediators of insulin resistance
      and beta-cell dysfunction?
AB  - In both type 1 and type 2 diabetes, diabetic complications in target organs arise
      from chronic elevations of glucose. The pathogenic effect of high glucose,
      possibly in concert with fatty acids, is mediated to a significant extent via
      increased production of reactive oxygen species (ROS) and reactive nitrogen
      species (RNS) and subsequent oxidative stress. ROS and RNS directly oxidize and
      damage DNA, proteins, and lipids. In addition to their ability to directly
      inflict damage on macromolecules, ROS and RNS indirectly induce damage to tissues
      by activating a number of cellular stress-sensitive pathways. These pathways
      include nuclear factor-kappaB, p38 mitogen-activated protein kinase, NH(2)
      terminal Jun kinases/stress-activated protein kinases, hexosamines, and others.
      In addition, there is evidence that in type 2 diabetes, the activation of these
      same pathways by elevations in glucose and free fatty acid (FFA) levels leads to
      both insulin resistance and impaired insulin secretion. Therefore, we propose
      here that the hyperglycemia-induced, and possibly FFA-induced, activation of
      stress pathways plays a key role in the development of not only the late
      complications in type 1 and type 2 diabetes, but also the insulin resistance and
      impaired insulin secretion seen in type 2 diabetes.

PMID- 12502487
TI  - Regulation of glycogen synthase by glucose and glycogen: a possible role for AMP
      activated protein kinase.
AB  - We report here use of human myoblasts in culture to study the relationships
      between cellular glycogen concentrations and the activities of glycogen synthase
      (GS) and AMP-activated protein kinase (AMPK). Incubation of cells for 2 h in the
      absence of glucose led to a 25% decrease in glycogen content and a significant
      decrease in the fractional activity of GS. This was accompanied by stimulation of
      both the alpha1 and alpha2 isoforms of AMPK, without significant alterations in
      the ratios of adenine nucleotides. When glucose was added to glycogen-depleted
      cells, a rapid and substantial increase in GS activity was accompanied by
      inactivation of AMPK back to basal values. Inclusion of the glycogen
      phosphorylase inhibitor, CP-91149, prevented the loss of glycogen during glucose
      deprivation but not the activation of AMPK. However, in the absence of prior
      glycogen breakdown, glucose treatment failed to activate GS above control values,
      indicating the crucial role of glycogen content. Activation of AMPK by either 5
      aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR) or hydrogen peroxide
      was also associated with a decrease in the activity ratio of GS. AICAR treatment
      had no effect on total cellular glycogen content but led to a modest increase in
      glucose uptake. These data support a role for AMPK in both stimulating glucose
      uptake and inhibiting GS in intact cells, thus promoting glucose flux through
      glycolysis.

PMID- 12502488
TI  - Plasma ghrelin concentrations are not regulated by glucose or insulin: a double
      blind, placebo-controlled crossover clamp study.
AB  - Ghrelin plasma concentrations increase during fasting and fall rapidly after
      nutrient ingestion. We hypothesized that insulin or glucose could regulate
      ghrelin secretion by a feedback mechanism. In this randomized, double-blind,
      placebo-controlled crossover study, three different study days were carried out
      in nine healthy volunteers (age 26 +/- 6 years). On each day, stepwise increasing
      systemic glucose concentrations of 5.0, 8.3, and 11.1 mmol/l were attained by
      intravenous infusion of glucose, representing fasting and postprandial
      conditions. Ghrelin plasma concentration was studied during concomitant exogenous
      hyperinsulinemia, inhibition of endogenous insulin production by somatostatin
      infusion, and placebo time control, respectively. Elevated glucose concentrations
      increased circulating insulin to 612 +/- 85 pmol/l (P < 0.01), but they did not
      affect ghrelin concentrations. Prolonged hyperinsulinemia by exogenous infusion
      resulted in circulating insulin of 1,602 +/- 261 pmol/l (P < 0.01) and suppressed
      plasma ghrelin to 49.6% of baseline (P < 0.01). During administration of
      somatostatin, insulin concentration remained constant, but an even greater
      decrease in ghrelin to 39.5% of baseline was noted (P < 0.01). Hyperglycemia does
      not decrease ghrelin, and a reduction in ghrelin is only seen at
      supraphysiological insulin concentrations. In contrast, systemic ghrelin
      concentrations are decreased by somatostatin. The meal-related suppression of
      ghrelin appears not directly regulated by glucose or insulin.

PMID- 12502489
TI  - Reduction of protein tyrosine phosphatase 1B increases insulin-dependent
      signaling in ob/ob mice.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin
      receptor (IR) signal transduction and a drug target for treatment of type 2
      diabetes. Using PTP1B antisense oligonucleotides (ASOs), effects of decreased
      PTP1B levels on insulin signaling in diabetic ob/ob mice were examined. Insulin
      stimulation, prior to sacrifice, resulted in no significant activation of insulin
      signaling pathways in livers from ob/ob mice. However, in PTP1B ASO-treated mice,
      in which PTP1B protein was decreased by 60% in liver, similar stimulation with
      insulin resulted in increased tyrosine phosphorylation of the IR and IR substrate
      (IRS)-1 and -2 by threefold, fourfold, and threefold, respectively. IRS-2
      associated phosphatidylinositol 3-kinase activity was also increased threefold.
      Protein kinase B (PKB) serine phosphorylation was increased sevenfold in liver of
      PTP1B ASO-treated mice upon insulin stimulation, while phosphorylation of PKB
      substrates, glycogen synthase kinase (GSK)-3alpha and -3beta, was increased more
      than twofold. Peripheral insulin signaling was increased by PTP1B ASO, as
      evidenced by increased phosphorylation of PKB in muscle of insulin-stimulated
      PTP1B ASO-treated animals despite the lack of measurable effects on muscle PTP1B
      protein. These results indicate that reduction of PTP1B is sufficient to increase
      insulin-dependent metabolic signaling and improve insulin sensitivity in a
      diabetic animal model.

PMID- 12502490
TI  - Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3
      kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high
      fat-fed obese rats.
AB  - Diet-induced obesity is known to cause peripheral insulin resistance in rodents.
      We have recently found that feeding cod protein to high-fat-fed rats prevents the
      development of insulin resistance in skeletal muscle. In the present study, we
      have further explored the cellular mechanisms behind this beneficial effect of
      cod protein on skeletal muscle insulin sensitivity. Rats were fed a standard chow
      diet or a high-fat diet in which the protein source was either casein, soy, or
      cod proteins for 4 weeks. Whole-body and muscle glucose disposal were reduced by
      approximately 50% in rats fed high-fat diets with casein or soy proteins, but
      these impairments were not observed in animals fed cod protein. Insulin-induced
      tyrosine phosphorylation of the insulin receptor and insulin receptor substrate
      (IRS) proteins were similar in muscle of chow- and high-fat-fed rats regardless
      of the dietary protein source. However, IRS-1-associated phosphatidylinositol
      (PI) 3-kinase activity was severely impaired (-60%) in muscle of high-fat-fed
      rats consuming casein or soy protein. In marked contrast, feeding rats with cod
      protein completely prevented the deleterious effect of fat feeding on insulin
      stimulated PI 3-kinase activity. The activation of the downstream kinase Akt/PKB
      by insulin, assessed by in vitro kinase assay and phosphorylation of GSK-3beta,
      were also impaired in muscle of high-fat-fed rats consuming casein or soy
      protein, but these defects were also fully prevented by dietary cod protein.
      However, no effect of cod protein was observed on atypical protein kinase C
      activity. Normalization of PI 3-kinase/Akt activation by insulin in rats fed high
      fat diets with cod protein was associated with improved translocation of GLUT4 to
      the T-tubules but not to the plasma membrane. Taken together, these results show
      that dietary cod protein is a natural insulin-sensitizing agent that appears to
      prevent obesity-linked muscle insulin resistance by normalizing insulin
      activation of the PI 3-kinase/Akt pathway and by selectively improving GLUT4
      translocation to the T-tubules.

PMID- 12502491
TI  - Elevated free fatty acids impair glucose metabolism in women: decreased
      stimulation of muscle glucose uptake and suppression of splanchnic glucose
      production during combined hyperinsulinemia and hyperglycemia.
AB  - The present study sought to determine whether elevated plasma free fatty acids
      (FFAs) alter the splanchnic and muscle glucose metabolism in women. To do so,
      FFAs were increased in seven women by an 8-h Intralipid/heparin (IL/hep)
      infusion, and the results were compared with those observed in nine women who
      were infused with glycerol alone. Glucose was clamped at approximately 8.3 mmol/l
      and insulin was increased to approximately 300 pmol/l to stimulate both muscle
      and hepatic glucose uptake. Insulin secretion was inhibited with somatostatin.
      Leg and splanchnic glucose metabolism were assessed using a combined catheter and
      tracer dilution approach. The glucose infusion rates required to maintain target
      plasma glucose concentrations were lower (P < 0.01) during IL/hep than glycerol
      infusion (30.8 +/- 2.6 vs. 65.0 +/- 7.9 micro mol. kg(-1). min(-1)). Whole-body
      glucose disappearance (37.0 +/- 2.2 vs. 70.9 +/- 8.7 micro mol. kg(-1). min(-1);
      P < 0.001) and leg glucose uptake (24.3 +/- 4.2 vs. 59.6 +/- 10.0 micro mol. kg
      fat-free mass of the leg(-1). min(-1); P < 0.02) were also lower, whereas
      splanchnic glucose production (8.2 +/- 0.8 vs. 4.3 +/- 0.7 micro mol. kg(-1).
      min(-1); P < 0.01) was higher during IL/hep than glycerol infusion. We conclude
      that in the presence of combined hyperinsulinemia and hyperglycemia, elevated
      FFAs impair glucose metabolism in women by inhibiting whole- body glucose
      disposal, muscle glucose uptake, and suppression of splanchnic glucose
      production.

PMID- 12502492
TI  - Differential regulation of lipogenesis and leptin production by independent
      signaling pathways and rosiglitazone during human adipocyte differentiation.
AB  - Since leptin levels are independently correlated with risk of coronary heart
      disease, we have identified signaling pathways important in mediating leptin
      production and lipogenesis in human preadipocytes. We used inhibitors of p70(S6)
      kinase, p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and
      phosphatidylinositol 3-kinase (PI3K). Human preadipocytes were induced to
      differentiate in insulin, dexamethasone, triiodothyronine, and 3-isobutyl-1
      methylxanthine in the presence or absence of inhibitors and the peroxisome
      proliferator-activated receptor (PPAR)-gamma activator rosiglitazone.
      Differentiation was assessed by measuring leptin secretion, lipid content, and
      lipogenic activity. Rosiglitazone increased cell protein by 15%, the lipid
      content of the cell layer was doubled, and the lipogenic activity increased
      sevenfold but did not stimulate leptin secretion. None of the inhibitors
      significantly inhibited protein content over 20 days, but lipid content and
      lipogenic activity were inhibited by p70(S6) kinase and p38 MAPK inhibition but
      not by p42/44 MAPK or PI3K inhibition. All of the inhibitors significantly
      decreased leptin secretion, and these inhibitory effects were increased by
      coincubation with rosiglitazone. We conclude that PI3K and p42/44 MAPK pathways
      are not critical to the differentiation program leading to lipid accumulation,
      but stimulation of leptin secretion is dependent on these as well as the p70(S6)
      kinase and p38 MAPK signaling pathways.

PMID- 12502493
TI  - Diabetes-induced, progressive endometrial involution characterization of
      periluminal epithelial lipoatrophy.
AB  - The present studies detail the cytopathological alterations in uterine
      epithelial, basal lamina, and stromal endometrial subregions, and associated
      endocrine parameters that occur during the progressive exacerbation of the
      diabetes syndrome in this species of mouse. These alterations result in a
      cellular lipoatrophic condition that compromises uterine tissue integrity and
      promotes reproductive involution. Uterine tissue samples were obtained from
      litter-matched control (+/?) and diabetic (db/db) C57BL/KsJ mice at four
      designated stages of the progressive expression of the diabetes mutation. In
      db/db mice between the ages of 4 and 12 weeks, the uterine epithelial cellular
      architecture exhibited progressive deterioration, characterized by cytoplasmic
      lipid imbibition (accumulation), organelle disintegration, apical membrane
      ciliary regression, and peristromal lamina separation from basal membrane
      surfaces, as compared with control indexes. The cytoplasmic volume occupied by
      lipid inclusions dominated the epithelial cells in diabetic mice, presenting
      dense basal pole lipid vacuoles, with perinuclear-intracytoplasmic migration of
      the inclusions promoting an apical cytoplasmic lipid condensation of increasing
      volume 8-12 weeks after mutation expression. These cytoplasmic lipid
      accumulations occurred under altered metabolic and endocrine conditions
      characterized by hyperglycemic, hyperinsulinemic, hypertriglyceridemic, and
      enhanced noradrenergic indexes, which were exacerbated between 4- and 12-week
      stages. These structural changes were accompanied by enhanced adrenergic
      counterregulatory metabolic responses as well as elevated lipoprotein and
      triacylglycerol lipase activities. These data indicate that diabetes-associated
      uterine involution is characterized by a progressive cellular and peristromal
      lipoatrophy of epithelial cell cytology and metabolic parameters, promoting
      stromal separation and ultimate endometrial involution.

PMID- 12502494
TI  - Purified allogeneic hematopoietic stem cell transplantation blocks diabetes
      pathogenesis in NOD mice.
AB  - Purified hematopoietic stem cells (HSCs) were transplanted into NOD mice to test
      whether development of hyperglycemia could be prevented. Engraftment of major
      histocompatibility complex-mismatched HSCs was compared with bone marrow (BM)
      grafts. HSCs differed from BM because HSCs were more strongly resisted and HSC
      recipients retained significant levels of NOD T-cells, whereas BM recipients were
      full donor chimeras. Despite persistent NOD T-cells, all HSC chimeras were
      protected from hyperglycemia, and attenuation of islet lesions was observed. T
      cell selection was altered in allogeneic HSC recipients as demonstrated by
      deletion of both donor and host superantigen-specific T-cells. Syngeneic and
      congenic hematopoietic cell transplants were also performed to differentiate the
      influence of the preparative regimen(s) versus the allografts. Unlike the
      allogeneic HSC transplantations, syngeneic or congenic grafts did not retard
      diabetes development. In a pilot study, overtly diabetic NOD mice were cured by
      co-transplantation of allogeneic HSCs and donor-matched islets. We conclude that
      allogeneic HSC transplants block allo- and autoimmunity, despite residual host T
      cell presence. These data demonstrate for the first time that purified HSC grafts
      block development of autoimmune diabetes and illuminate how HSC grafts alter
      thymic and peripheral T-cell responses against auto- and alloantigens.

PMID- 12502495
TI  - Survival and maturation of microencapsulated porcine neonatal pancreatic cell
      clusters transplanted into immunocompetent diabetic mice.
AB  - Differentiation and maturation of porcine neonatal pancreatic cell clusters
      (NPCCs) microencapsulated in barium alginate were assessed after transplantation
      into immunocompetent mice. Microencapsulated NPCCs were transplanted into the
      peritoneal cavity of streptozocin-induced diabetic B6AF1 mice (n = 32). The
      microcapsules were removed at 2, 6, and 20 weeks and examined for cellular
      overgrowth, insulin content, and insulin secretory responses to glucose and
      glucose with theophylline. The differentiation, maturation, and proliferation of
      the beta-cells in the NPCCs were assessed by immunohistochemistry. Blood glucose
      levels were normalized in 81% of the animals that received a transplant and
      remained normal until termination of the experiments at 20 weeks. Hyperglycemic
      blood glucose levels after explantation of the capsules confirmed the function of
      the encapsulated NPCCs. Insulin content of the encapsulated NPCCs was increased
      10-fold at 20 weeks after transplantation compared with pretransplantation
      levels. A 3.2-fold increase of the ratio of the beta-cell area to the total
      cellular area was observed at 20 weeks, demonstrating the maturation of NPCCs
      into beta-cells. In conclusion, NPCCs encapsulated with simple barium alginate
      can differentiate into beta-cells and reverse high blood glucose levels in
      immunocompetent mice without immunosuppression for >20 weeks.

PMID- 12502496
TI  - All-trans retinoic acid induces differentiation of ducts and endocrine cells by
      mesenchymal/epithelial interactions in embryonic pancreas.
AB  - Retinoids during the embryonic period act as a mesenchymal inducer in many
      organs, including kidney, lung, central nervous system, and gut. Retinoic acid
      (RA) demonstrates insulinotropic effects in adult pancreas, but only a limited
      study has elucidated its role in pancreatic organogenesis. In this study, we have
      analyzed the existence of RA-signaling machinery in embryonic pancreas and
      evaluated its role using in vitro tissue culture experiments. Here we show the
      presence of endogenous retinaldehyde dehydrogenase 2 (RALDH2), the most effective
      RA-synthesizing enzyme, RA-binding proteins, and RA receptors (RARs) in embryonic
      pancreatic tissue. RALDH2 is expressed exclusively in the mesenchyme. Exogenously
      added all-trans-retinoic acid (atRA) in tissue culture experiments stimulated
      differentiation of endocrine and duct cells and promoted apoptotic cell death of
      acinar tissue. Furthermore, we demonstrate that atRA upregulates the PDX-1
      expression. Taken together, our data suggest that atRA-mediated
      mesenchymal/epithelial interactions play an important role in determining the
      cell fate of epithelial cells via regulation of the PDX-1 gene, leading to the
      proper formation of the endocrine versus exocrine component during pancreatic
      organogenesis.

PMID- 12502497
TI  - Role for VPAC2 receptor-mediated signals in pancreas development.
AB  - Mature pancreatic cells develop from progenitors that proliferate and
      differentiate into endocrine and exocrine cells. This development is thought to
      be controlled by secreted soluble factors acting on their target cells after
      binding to membrane receptors. Here, we analyzed the impact on embryonic
      pancreatic development of ligands that bind to protein G-coupled receptors and
      increase cAMP accumulation. We found that embryonic pancreatic epithelial cells
      were sensitive to vasoactive intestinal peptide (VIP) and pituitary adenylate
      cyclase-activating polypeptide. These factors generate signals after binding to
      the VPAC2 receptor, which is expressed by immature pancreatic epithelial cells
      between embryonic days 12 and 16. Finally, in vitro, VIP exposure increased the
      survival and proliferation of immature pancreatic cells, leading to an increase
      in the number of endocrine cells that will develop.

PMID- 12502498
TI  - Improvement of the mitochondrial antioxidant defense status prevents cytokine
      induced nuclear factor-kappaB activation in insulin-producing cells.
AB  - Proinflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor
      alpha [TNF-alpha], and gamma-interferon [IFN-gamma]) initiate a variety of signal
      cascades in pancreatic beta-cells that affect the expression level of genes
      involved in both the destruction and the protection of the beta-cell. The
      generation of nitric oxide (NO) via the inducible NO synthase (iNOS) and oxygen
      free radicals play a key role in cytokine-mediated beta-cell destruction. Within
      these signal cascades, the activation of the transcription factor nuclear factor
      kappaB (NF-kappaB) is crucial, and many cytokine-sensitive genes contain binding
      sites for this transcription factor in their promoter regions. The aim of this
      study was to characterize the cytokine-mediated activation of NF-kappaB and the
      subsequent expression of iNOS protein in insulin-producing RINm5F cells with an
      improved antioxidant defense status by overexpression of the cytoprotective
      enzymes catalase (Cat), glutathione peroxidase (Gpx), and the cytoplasmic Cu/Zn
      superoxide dismutase (Cu/ZnSOD). RINm5F cells with diverse mitochondrial
      antioxidative defense status were generated by stable overexpression of MnSOD
      constructs in sense (MnSOD sense) and antisense orientation (MnSOD antisense).
      Cytokine-induced (IL-1beta or cytokine mix consisting of IL-1beta + TNF-alpha +
      IFN-gamma) activation of NF-kappaB in RINm5F cells was reduced by >80% through
      overexpression of MnSOD. The activity of the iNOS promoter remained at basal
      levels in cytokine-stimulated MnSOD sense cells. In contrast, the suppression of
      MnSOD gene expression in cytokine-stimulated MnSOD antisense cells resulted in a
      threefold higher activation of NF-kappaB and a twofold higher activation of the
      iNOS promoter as compared with control cells. The iNOS protein expression was
      significantly reduced after a 6- and 8-h cytokine incubation of MnSOD sense
      cells. The low activity level of MnSOD in RINm5F MnSOD antisense cells increased
      the iNOS protein expression in particular during the early phase of cytokine
      mediated toxicity. Cat, Gpx, and the cytoplasmic Cu/ZnSOD did not affect the
      activation of NF-kappaB and the iNOS promoter. In conclusion, the overexpression
      of MnSOD, which inactivates specifically mitochondrially derived oxygen free
      radicals, significantly reduced the activation of NF-kappaB in insulin-producing
      cells. As a consequence of this protective effect in the early cytokine signaling
      pathways, the induction of iNOS, an important event in the beta-cell destruction
      process, was also significantly reduced. The results provide evidence that
      mitochondrially derived reactive oxygen species (ROS) play a critical role in the
      activation of the cytokine-sensitive transcription factor NF-kappaB.
      Overexpression of MnSOD may thus be beneficial for beta-cell survival through
      suppression of oxygen free radical formation, prevention of NF-kappaB activation,
      and iNOS expression.

PMID- 12502499
TI  - Beta-cell deficit and increased beta-cell apoptosis in humans with type 2
      diabetes.
AB  - Type 2 diabetes is characterized by impaired insulin secretion. Some but not all
      studies suggest that a decrease in beta-cell mass contributes to this. We
      examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2);
      41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35
      nondiabetic subjects) and 33 lean cases (BMI <25 kg/m(2); 16 type 2 diabetic and
      17 nondiabetic subjects). We measured relative beta-cell volume, frequency of
      beta-cell apoptosis and replication, and new islet formation from exocrine ducts
      (neogenesis). Relative beta-cell volume was increased in obese versus lean
      nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P <
      0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P
      < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in
      relative beta-cell volume compared with nondiabetic obese and lean cases,
      respectively. The frequency of beta-cell replication was very low in all cases
      and no different among groups. Neogenesis, while increased with obesity, was
      comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean
      type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell
      apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2
      diabetes compared with their respective nondiabetic control group (P < 0.05). We
      conclude that beta-cell mass is decreased in type 2 diabetes and that the
      mechanism underlying this is increased beta-cell apoptosis. Since the major
      defect leading to a decrease in beta-cell mass in type 2 diabetes is increased
      apoptosis, while new islet formation and beta-cell replication are normal,
      therapeutic approaches designed to arrest apoptosis could be a significant new
      development in the management of type 2 diabetes, because this approach might
      actually reverse the disease to a degree rather than just palliate glycemia.

PMID- 12502500
TI  - Glucose regulates the release of orexin-a from the endocrine pancreas.
AB  - Orexins (hypocretins) are novel neuropeptides that appear to play a role in the
      regulation of energy balances. Orexin-A (OXA) increases food intake in rodents,
      and fasting activates OXA neurons in both the lateral hypothalamic area and gut.
      OXA is also found in the endocrine pancreas; however, little is known about its
      release or functional significance. In this study, we show that depolarizing
      stimuli evoke the release of OXA from rat pancreatic islets in a calcium
      dependent manner. Moreover, OXA release is stimulated by low glucose (2.8
      mmol/l), similar to glucagon secretion, and inhibited by high glucose (16.7
      mmol/l). Fasting increases plasma OXA, supporting the idea that orexin is
      released in response to hypoglycemia. Cells that secrete glucagon and insulin
      contain OXA and both cell types express orexin receptors. OXA increases glucagon
      secretion and decreases glucose-stimulated insulin release from isolated islets.
      OXA infusion increases plasma glucagon and glucose levels and decreases plasma
      insulin in fasted rats. We conclude that orexin-containing islet cells, like
      those in the brain and gut, are glucosensitive and part of a network of glucose
      "sensing" cells that becomes activated when blood glucose levels fall. OXA may
      modulate islet hormone secretion to maintain blood glucose levels during fasting.

PMID- 12502501
TI  - Measurements of insulin secretory capacity and glucose tolerance to predict
      pancreatic beta-cell mass in vivo in the nicotinamide/streptozotocin Gottingen
      minipig, a model of moderate insulin deficiency and diabetes.
AB  - Knowledge about beta-cell mass and/or function could be of importance for the
      early diagnosis and treatment of diabetes. However, measurement of beta-cell
      function as an estimate of beta-cell mass is currently the only method possible
      in humans. The present study was performed to investigate different functional
      tests as predictors of beta-cell mass in the Gottingen minipig. beta-cell mass
      was reduced in the Gottingen minipig with a combination of nicotinamide (100 [n =
      6], 67 [n = 25], 20 [n = 2], or 0 mg/kg [n = 4]) and streptozotocin (125 mg/kg).
      Six normal pigs were included. An oral glucose tolerance test (OGTT) (n = 43) and
      insulin secretion test (n = 30) were performed and pancreata obtained for
      stereological determination of beta-cell mass. During OGTT, fasting glucose (r(2)
      = 0.1744, P < 0.01), area under the curve for glucose (r(2) = 0.2706, P < 0.001),
      maximum insulin secretion (r(2) = 0.2160, P < 0.01), and maximum C-peptide
      secretion (r(2) = 0.1992, P < 0.01) correlated with beta-cell mass. During the
      insulin secretion test, acute insulin response to 0.3 g/kg (r(2) = 0.6155, P <
      0.0001) and 0.6 g/kg glucose (r(2) = 0.7321, P < 0.0001) and arginine (67 mg/kg)
      (r(2) = 0.7732, P < 0.0001) and maximum insulin secretion (r(2) = 0.8192, P <
      0.0001) correlated with beta-cell mass. This study supports the use of functional
      tests to evaluate beta-cell mass in vivo and has established a validated basis
      for developing a mathematical method for estimation of beta-cell mass in vivo in
      the Gottingen minipig.

PMID- 12502502
TI  - Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via
      transactivation of the epidermal growth factor receptor.
AB  - We previously provided evidence that glucagon-like peptide 1 (GLP-1) induces
      pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol
      (PI) 3-kinase- and protein kinase C zeta-dependent manner. However, the exact
      mechanism by which the GLP-1 receptor (GLP-1R), a member of the G protein-coupled
      receptor (GPCR) superfamily, activates the PI 3-kinase signaling pathway to
      promote beta-cell growth remains unknown. We hypothesized that the GLP-1R could
      activate PI 3-kinase and promote beta-cell proliferation through transactivation
      of the epidermal growth factor (EGF) receptor (EGFR), an event possibly linked to
      GPCRs via activation of c-Src and the production of putative endogenous EGF-like
      ligands. Both the c-Src inhibitor PP1 and the EGFR-specific inhibitor AG1478
      blocked GLP-1-induced [(3)H]thymidine incorporation in INS(832/13) cells as well
      as in isolated rat islets, while only AG1478 inhibited the proliferative action
      of betacellulin (BTC), an EGFR agonist. Both compounds also suppressed GLP-1
      induced PI 3-kinase activation. A time-dependent increase in tyrosine
      phosphorylation of the EGFR in response to GLP-1 was observed in INS(832/13)
      cells. This transactivation of the EGFR was sensitive to both the pharmacological
      agents PP1 and AG1478. The action of GLP-1 and BTC on INS cell proliferation was
      found to be not additive. Overexpression of a dominant-negative EGFR in INS cells
      with a retroviral expression vector curtailed GLP-1-induced beta-cell
      proliferation. GLP-1 treatment of INS cells caused a decrease in cell surface
      associated BTC, as shown by FACS analysis. Also, the metalloproteinase inhibitor
      GM6001 and an anti-BTC neutralizing antibody suppressed the GLP-1 proliferative
      effect. Finally, coculturing the prostatic cancer cell line LNCaP that lacks GLP
      1 responsiveness with INS cells increased LNCaP cell proliferation in the
      presence of GLP-1, thus revealing that INS cells secrete a growth factor in
      response to GLP-1. GM6001 and an anti-BTC neutralizing antibody suppressed
      increased LNCaP cell proliferation in the presence of GLP-1 in the coculture
      experiments. The results are consistent with a model in which GLP-1 increases PI
      3-kinase activity and enhances beta-cell proliferation via transactivation of the
      EGFR that would require the proteolytic processing of membrane-anchored BTC or
      other EGF-like ligands.

PMID- 12502503
TI  - Effects of acute insulin excess and deficiency on gluconeogenesis and
      glycogenolysis in type 1 diabetes.
AB  - To determine whether insulin induces acute changes in endogenous glucose
      production (EGP) via changes in gluconeogenesis (GNG), glycogenolysis (GL), or
      both, we measured GNG (with (2)H(2)O) and GL (EGP-GNG) in nine patients with type
      1 diabetes during acute insulin excess produced by subcutaneous injection of
      insulin and during insulin deficiency which developed between 5 and 8 h after
      insulin injection. During insulin excess, free insulin concentration rose
      fivefold (from 36 to 180 pmol/l). Plasma glucose was maintained between 6.2 and
      6.7 mmol/l for approximately 4 h with IV glucose. EGP (with 6,6-(2)H glucose)
      decreased from 17.1 to 9.8 micro mol. kg(-1). min(-1) after 1 h. This decrease
      was almost completely accounted for by a decrease in GL (from 10.7 to 4.6 micro
      mol. kg(-1). min(-1)). During insulin deficiency, plasma glucose rose from 6.2 to
      10.5 mmol/l and EGP from 9.5 to 14.3 micro mol/kg min. The increase in EGP again
      was accounted for by an increase in GL. We conclude that in type 1 diabetes acute
      regulation of EGP by insulin is mainly via changes in GL while GNG changes little
      during the early hours of acute insulin excess or deficiency.

PMID- 12502504
TI  - Intramyocellular lipid and insulin resistance: a longitudinal in vivo 1H
      spectroscopic study in Zucker diabetic fatty rats.
AB  - Insulin resistance plays an important role in the pathogenesis of human type 2
      diabetes. In humans, a negative correlation between insulin sensitivity and
      intramyocellular lipid (IMCL) content has been shown; thus, IMCL becomes a marker
      for insulin resistance. Recently, magnetic resonance spectroscopy (MRS) has been
      established as a dependable method for selective detection and quantification of
      IMCL in humans. To validate the interrelation between insulin sensitivity and
      IMCL in an animal model of type 2 diabetes, we established volume selective (1)H
      MRS at 7 Tesla to noninvasively assess IMCL in the rat. In male obese Zucker
      Diabetic Fatty rats and their lean littermates, IMCL levels were determined
      repeatedly over 4 months, and insulin sensitivity was measured by the euglycemic
      hyperinsulinemic clamp method at 6-7 and at 22-24 weeks of age. A distinct
      relation between IMCL and insulin sensitivity was demonstrated as well as age
      dependence for both parameters. Rosiglitazone treatment caused a clear reduction
      of IMCL and hepatic fat despite increased body weight, and a marked improvement
      of insulin sensitivity. Thus, the insulin sensitizing properties of rosiglitazone
      were consistent with a redistribution of lipids from nonadipocytic (skeletal
      muscle, liver) back into fat tissue.

PMID- 12502505
TI  - Apolipoprotein-e influences aspects of intellectual ability in type 1 diabetes.
AB  - The epsilon4 allele of the apolipoprotein-E (APOE) gene is associated with poor
      outcome following various cerebral insults. The relationship between APOE
      genotype and cognitive function in patients with type 1 diabetes is unknown. In a
      cross-sectional study of 96 people with type 1 diabetes, subjects were APOE
      genotyped, previous exposure to severe hypoglycemia was estimated by
      questionnaire, and cognition was assessed by neuropsychological testing.
      Cognitive abilities were compared using multivariate general linear modeling
      (multiple analysis of covariance, MANCOVA) in those with (n = 21) and without (n
      = 75) the APOE epsilon4 allele. APOE epsilon4 selectively influenced cognitive
      ability in a sex-specific manner (F = 2.3, P = 0.044, Eta(2) = 0.15); women with
      APOE epsilon4 performed less well on tests of current, nonverbal intellectual
      ability (Wechsler Adult Intelligence Scale-Revised performance test score, P =
      0.001, Eta(2) 0.26) and frontal lobe and executive function (Borkowski verbal
      fluency, P = 0.016, Eta(2) = 0.15). Previous exposure to severe hypoglycemia did
      not interact with APOE epsilon4 to produce cognitive disadvantage. The APOE
      epsilon4 genotype is associated with specific cognitive disadvantage in young
      women with type 1 diabetes. APOE epsilon4 is unlikely to mediate susceptibility
      to hypoglycemia-induced cognitive disadvantage.

PMID- 12502506
TI  - Cognitive ability and brain structure in type 1 diabetes: relation to
      microangiopathy and preceding severe hypoglycemia.
AB  - Type 1 diabetes is associated with chronic hyperglycemia and exposure to
      intermittent severe hypoglycemia. The long-term cerebral effects of these
      consequences of diabetes are ill defined. In this study, the history of preceding
      severe hypoglycemia and the presence of background retinopathy were examined in
      relation to cognitive ability (neuropsychological test battery) and brain
      structure (magnetic resonance imaging) in a cross-sectional evaluation of 74
      young people with type 1 diabetes. Participants differed by their severe
      hypoglycemia exposure and degree of diabetic retinopathy and none had previous
      neuropsychological pathology. Severe hypoglycemia did not influence cognitive
      ability or brain structure. Background diabetic retinopathy was associated with
      small focal white-matter hyperintensities in the basal ganglia (33.3 vs. 4.7%,
      after correction for age, P = 0.005) and significant cognitive disadvantage,
      affecting fluid intelligence (P = 0.008, Eta(2) = 0.14), information processing
      (P = 0.001, Eta(2) = 0.22), and attention and concentration ability (P = 0.03,
      Eta(2) = 0.09). In conclusion, recurrent exposure to severe hypoglycemia alone in
      young people with type 1 diabetes had no detrimental impact on brain structure or
      function over the duration of diabetes examined. Chronic hyperglycemia (inferred
      by the presence of background diabetic retinopathy) may affect brain structure
      and function.

PMID- 12502507
TI  - The effectiveness of treatments of diabetic autonomic neuropathy is not the same
      in autonomic nerves supplying different organs.
AB  - The aim of the study was to investigate antioxidant (alpha-lipoic acid [LA]) and
      gamma-linolenic acid treatments in the prevention of changes in autonomic nerves
      induced in streptozotocin-diabetic rats. Autonomic nerves supplying the heart,
      penis, and gut were examined using immunohistochemical and biochemical
      techniques. LA and gamma-linolenic acid (present in evening primrose oil [EPO])
      were administered as dietary supplements ( approximately 80 and 200 mg. kg(-1).
      day(-1), respectively). LA treatment prevented the diabetes-induced decrease of
      norepinephrine (NA) in the heart and of type I nitric oxide synthase (NOS-I)
      expression in erectile tissue of the penis but failed to prevent diabetes-induced
      changes in NA-, vasoactive intestinal polypeptide-, or calcitonin gene-related
      peptide-containing nerves supplying the ileum. LA partially prevented and EPO
      totally prevented the increase in NOS-I activity induced by diabetes in the
      ileum. EPO treatment failed to prevent any other diabetes-induced changes in the
      heart, penis, or ileum. These results demonstrate that, whereas LA treatment is
      more effective than EPO in preventing diabetes-induced changes in autonomic
      nerves, the effectiveness of LA treatment varies with the target organ studied.
      Diabetes-induced changes in nerves supplying the ileum are more resistant to
      treatment than those of the heart and penis.

PMID- 12502508
TI  - Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic
      experimental diabetic neuropathy.
AB  - We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion
      (DRG) neurons using immunohistochemical and electrophysiologic techniques for
      evidence of oxidative injury. Experimental diabetic neuropathy was induced by
      streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied
      peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic
      abnormalities were present from the first month and persisted over 12 months. 8
      Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points
      in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly
      increased at all three time points, indicating commitment to the efferent limb of
      the apoptotic pathway. Apoptosis was confirmed by a significant increase in the
      percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12
      months (11%). These findings support the concept that oxidative stress leads to
      oxidative injury of DRG neurons, with mitochondrium as a specific target, leading
      to impaired mitochondrial function and apoptosis, manifested clinically as a
      predominantly sensory neuropathy.

PMID- 12502509
TI  - The atherogenic lipoprotein profile associated with obesity and insulin
      resistance is largely attributable to intra-abdominal fat.
AB  - Obesity and insulin resistance are both associated with an atherogenic
      lipoprotein profile. We examined the effect of insulin sensitivity and central
      adiposity on lipoproteins in 196 individuals (75 men and 121 women) with an
      average age of 52.7 years. Subjects were subdivided into three groups based on
      BMI and their insulin sensitivity index (S(I)): lean insulin sensitive (n = 65),
      lean insulin resistant (n = 73), and obese insulin resistant (n = 58). This
      categorization revealed that both obesity and insulin resistance determined the
      lipoprotein profile. In addition, the insulin-resistant groups had increased
      central adiposity. Increasing intra-abdominal fat (IAF) area, quantified by
      computed tomography scan and decreasing S(I), were important determinants of an
      atherogenic profile, marked by increased triglycerides, LDL cholesterol, and
      apolipoprotein B and decreased HDL cholesterol and LDL buoyancy (Rf). Density
      gradient ultracentrifugation (DGUC) revealed that in subjects who had more IAF
      and were more insulin resistant, the cholesterol content was increased in VLDL,
      intermediate-density lipoprotein (IDL), and dense LDL fractions whereas it was
      reduced in HDL fractions. Multiple linear regression analysis of the relation
      between the cholesterol content of each DGUC fraction as the dependent variable
      and IAF and S(I) as independent variables revealed that the cholesterol
      concentration in the fractions corresponding to VLDL, IDL, dense LDL, and HDL was
      associated with IAF, and that S(I) additionally contributed independently to
      VLDL, but not to IDL, LDL, or HDL. Thus an atherogenic lipoprotein profile
      appears to be the result primarily of an increase in IAF, perhaps via insulin
      resistance.

PMID- 12502510
TI  - Combinations of nondiabetic parental genomes elicit impaired glucose tolerance in
      mouse SMXA recombinant inbred strains.
AB  - Type 2 diabetes in humans is not a single gene disorder but a multifactorial
      disease caused by the interaction of multiple genes and environmental factors.
      Recombinant inbred (RI) strains are a powerful tool for analyzing not only single
      genetic traits but also multifactorial genetic traits. By using the SMXA RI mice,
      we genetically dissected diabetes-related traits (BMI, nonfasting blood glucose
      concentration, and blood glucose concentration during intraperitoneal glucose
      tolerance tests). For minimizing the variation of glucose tolerance in each
      strain, all mice were fed the high-carbohydrate diet and subjected to phenotypic
      and genetic analyses. The parental strains, SM/J and A/J, were nondiabetic, and
      the differences of the mean values of diabetes-related traits were small. In
      contrast, an impaired glucose tolerance was observed in (SM x A)F1 mice, and
      marked differences in diabetes-related traits were observed in 19 SMXA RI
      strains. In particular, several SMXA RI strains showed markedly impaired glucose
      tolerance and hyperglycemia. Quantitative trait locus (QTL) analysis revealed a
      locus on chromosome (Chr) 10 contributing significant effect on nonfasting blood
      glucose concentration, as well as six diabetes-related loci on four chromosomes
      with suggestive evidence of linkage with diabetes-related phenotypes. The A/J
      derived QTLs on Chr 2 and 18 and an SM/J-derived QTL on Chr 10 contributed to the
      impairment of glucose tolerance and/or the increase of blood glucose
      concentration. The present study indicates that QTLs derived from parental SM/J
      and A/J genomes, both of which are nondiabetic, interact in the RI genomes,
      leading to the development of hyperglycemia and diabetic phenotypes. Genetic
      dissection of this kind of diabetogenesis will increase our understanding of the
      complex gene-gene interaction and mode of inheritance in human type 2 diabetes.

PMID- 12502511
TI  - The insulin gene variable number tandem repeat class I/III polymorphism is in
      linkage disequilibrium with birth weight but not Type 2 diabetes in the Pima
      population.
AB  - The insulin gene variable number tandem repeat (INS-VNTR) is proposed to exert
      pleiotropic genetic effects on birth weight and diabetes susceptibility. In our
      study, we examined the influence of a polymorphism in tight linkage
      disequilibrium with INS-VNTR (-23Hph1) on birth weight and type 2 diabetes in the
      Pima population. A parent-offspring "trio" design was used to assess parent-of
      origin effects and population stratification. The presence of the -23Hph1 T
      allele was associated with lower birth weight (n = 192; -140 g per copy of the T
      allele; P = 0.04), even after adjustment for effects of population stratification
      (P = 0.03). The effects of paternally transmitted T-alleles were greater than
      those of maternally transmitted alleles (paternally transmitted: -250 g, P =
      0.05; maternally transmitted: -111 g, P = 0.43), but this difference was not
      statistically significant (P = 0.50). The -23Hph1 T-allele was associated with an
      increased prevalence of type 2 diabetes (P = 0.009), which family-based
      association analysis suggested was attributable to population structure (P =
      0.04) without significant evidence of linkage disequilibrium between diabetes
      prevalence and genotype (P = 0.86). Thus allelic variation of the INS gene is
      associated with lower birth weight and increased prevalence of type 2 diabetes.
      Significant linkage disequilibrium was found between -23Hph1 and birth weight but
      not type 2 diabetes, an observation that supports a potential functional role of
      INS polymorphisms in the regulation of birth weight.

PMID- 12502512
TI  - Impact of two common polymorphisms in the PPARgamma gene on glucose tolerance and
      plasma insulin profiles in monozygotic and dizygotic twins: thrifty genotype,
      thrifty phenotype, or both?
AB  - The Pro12Ala polymorphism in the PPARgamma2 gene has been associated with reduced
      risk of type 2 diabetes and insulin resistance. Recently, an association between
      dizygotic twinning and PPARgamma gene polymorphisms has been proposed. We
      investigated the phenotypic appearance of the two polymorphisms (Pro12Ala and
      exon 6 C-->T) in PPARgamma among elderly twins (207 monozygotic [MZ] and 342
      dizygotic [DZ]) and evaluated whether they could explain previously reported
      differences in plasma glucose and insulin profiles among MZ and DZ twins. We
      demonstrated a significant impact of the Pro12Ala polymorphism on glucose
      tolerance, diabetic status, homeostasis model assessment for insulin resistance,
      and plasma insulin profiles in twins. No impact of the silent exon 6 polymorphism
      on glucose homeostasis or plasma insulin profiles was found. Independent of the
      polymorphisms, we observed a significant impact of zygosity status per se on the
      plasma insulin profile after oral glucose ingestion, with the MZ twins being more
      hyperinsulinemic, indicating insulin resistance, than the DZ twins.
      Nonsignificantly higher glucose concentrations were observed among MZ compared
      with DZ twins. We demonstrated an association between the Ala allele and reduced
      risk of diabetes and insulin resistance in twins. However, the differences in
      metabolic profiles among MZ and DZ twins were not explained by differences in
      frequencies of the genetic variants and may be due to intrauterine environmental
      factors operating in twins independent of genotype. Accordingly, our study
      simultaneously supports a role for both the intrauterine environment (thrifty
      phenotype) and for genetics (thrifty genotype) in the etiology of insulin
      resistance and perhaps glucose intolerance in twins.

PMID- 12502513
TI  - Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant
      trait characterized by abnormal pyruvate-induced insulin release.
AB  - We have identified patients in whom strenuous physical exercise leads to
      hypoglycemia caused by inappropriate insulin release (exercise-induced
      hyperinsulinism [EIHI]). The aim of the present study was to test the hypothesis
      that the increased levels of lactate and/or pyruvate during anaerobic exercise
      would trigger the aberrant insulin secretion in these patients. A total of 12
      patients (8 women and 4 men from two families) were diagnosed with EIHI, based on
      hypoglycemia and a more than threefold increase in plasma insulin induced by a 10
      min bicycle exercise test. The mode of inheritance was autosomal dominant in
      these families. The acute response of insulin release to a bolus of intravenous
      pyruvate (13.9 mmol/1.73 m(2)) was studied in the patients and eight healthy
      control subjects. Insulin secretion did not respond to the pyruvate bolus in
      healthy control subjects. However, all EIHI patients responded to pyruvate,
      displaying a brisk increase in plasma insulin. The 1 + 3-min peak response was
      5.6-fold in the patients and 0.9-fold in the control subjects (P < 0.001). To
      test the hypothesis that the pathogenesis of EIHI would involve monocarboxylate
      transport or metabolism in the beta-cell, we sequenced the genes encoding the
      known monocarboxylate transporter proteins and tested the transport of pyruvate
      into patient fibroblasts. The results revealed normal coding sequences and
      pyruvate transport. In conclusion, EIHI represents a new autosomal-dominant
      hyperinsulinemia syndrome that may be more common than has been realized. The
      pyruvate test provides a simple, safe, and specific diagnostic test for this
      condition.

PMID- 12502514
TI  - The derivation of highly germline-competent embryonic stem cells containing NOD
      derived genome.
AB  - It would be extremely advantageous to the analysis of disease mechanisms in the
      spontaneous mouse model of type 1 diabetes, the nonobese diabetic (NOD) strain,
      if genes in this strain could be modified in vivo using embryonic stem (ES) cells
      and homologous recombination. However, a NOD ES cell line with adequate germline
      transmission has not yet been reported. We report the development of highly
      germline-competent ES cell lines from the F1 hybrid of NOD and 129 for use in NOD
      gene targeting. Consequently, we developed ES cell lines derived from (NOD x
      129)F1 x 129 backcross 1 mice, which were intercrossed to select for homozygosity
      of particular regions of NOD genome known to contain disease loci.

PMID- 12502515
TI  - Mapping genes influencing type 2 diabetes risk and BMI in Japanese subjects.
AB  - We have carried out an autosomal genome scan for genes contributing to the
      development of type 2 diabetes and affecting BMI in the Japanese population (164
      families, 256 affected sib-pairs). We found 12 regions that showed nominally
      significant multipoint evidence of linkage with type 2 diabetes (i.e. logarithm
      of odds [LOD] score >0.59, P < 0.05): chromosome 1 29.9 cM; chromosome 2 169.6
      and 236.8 cM; chromosome 4 104.9 cM; chromosome 5 114.8 cM; chromosome 6 42.3 cM;
      chromosome 8 15.3 and 93.3 cM; chromosome 9 140.0 cM; chromosome 11 131.6 cM;
      chromosome 17 36.1 cM; and chromosome 21 48.0 cM. Twelve regions showed nominal
      multipoint evidence for linkage with log-transformed BMI (lnBMI): chromosome 2
      167.9 and 210.5 cM; chromosome 3 185.7 cM; chromosome 4 118.9 and 145.6 cM;
      chromosome 5 131.9 cM; chromosome 7 7.4 cM; chromosome 10 70.0 cM; chromosome 15
      12.8 cM; chromosome 16 30.0 cM; and chromosome 17 47.8 and 100.2 cM. Although
      none of the regions achieved genome-wide levels of significance, simulation
      studies showed that we observed more linkage signals than expected if there were
      no loci contributing to type 2 diabetes or BMI. Eight of the regions showing
      nominal evidence for linkage with type 2 diabetes have been reported in other
      genome scans, and seven of the regions showing linkage with lnBMI have shown
      linkage with BMI and BMI-related traits in other studies. Thus, our results may
      replicate findings in other studies. They may also indicate new regions of the
      genome that are involved in the regulation of blood glucose levels or body
      weight.

PMID- 12502516
TI  - Variation in resistin gene promoter not associated with polycystic ovary
      syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility
      and affects approximately 4-7% of reproductive age women in the U.S. It is
      characterized by hyperandrogenemia and chronic anovulation and is associated with
      insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen
      of candidate genes, a region on chromosome 19p13.3 was identified that shows
      significant evidence for both linkage and association with PCOS. A promising
      candidate gene for PCOS, resistin, maps to exactly this region. Resistin is a
      protein hormone thought to modulate glucose tolerance and insulin action. We
      tested for association between a single nucleotide polymorphism in the promoter
      region of the resistin gene and three phenotypes: PCOS, obesity, and insulin
      resistance. We did not find evidence for association with any of the phenotypes.
      It is therefore unlikely that variation in the resistin gene accounts for the
      strong association that we observe between chromosome 19p13.3 and PCOS. Instead,
      this association is most likely due to a gene or genetic element in this region
      that has not been identified.

PMID- 12502517
TI  - A susceptibility allele from a non-diabetes-prone mouse strain accelerates
      diabetes in NOD congenic mice.
AB  - The nonobese diabetic (NOD) mouse is genetically predisposed for the spontaneous
      development of type 1 diabetes. Linkage analyses have identified at least 19
      susceptibility loci (Idd1-Idd19) that contribute to disease pathogenesis in which
      lymphocytes mediate the specific destruction of insulin-producing beta-cells.
      Interestingly, nondiabetic mouse strains have been shown to confer susceptibility
      alleles to affected progeny in NOD outcrosses for some of the Idd loci. In
      particular, we noted that diabetic backcross progeny, derived from NOD and
      C57BL/6 (B6) mouse strains, demonstrated increased heterozygousity for an
      interval encompassing Idd14 on chromosome 13. This result suggested that B6 mice
      harbor a more diabetogenic allele(s) than NOD mice for this locus. To confirm
      this observation, a NOD congenic mouse strain, containing a B6-derived interval
      covering the majority of chromosome 13, was generated. Adding to the combination
      of already potent susceptibility alleles elsewhere in the NOD genome, the
      chromosome 13 B6-derived interval was able to increase the overall risk of
      developing type 1 diabetes, which resulted in an earlier onset and increased
      incidence of type 1 diabetes in congenic mice as compared with NOD mice.
      Furthermore, this B6-derived interval, in combination with the NOD genetic
      background, was able to overcome environmental conditions that typically
      suppressed type 1 diabetes in the NOD mouse strain.

PMID- 12502519
TI  - Effects of gastrin-releasing peptide 1-27 on taste responses in the rat.
AB  - Gastrin-releasing-peptide(1-27) (GRP) has been implicated in the regulation of
      satiety and appetite in numerous paradigms. However, the specific site and mode
      of action of this gut-brain peptide has not been elucidated. The following
      experiment examined the effects of GRP on taste responses to sucrose in the
      behaving rat. A brief-exposure, multi-bottle gustometer was used to provide rats
      with momentary access to six different concentrations of sucrose in a single test
      session. This procedure has been used previously, resulting in monotonically
      increased licking behavior as concentrations of sucrose increase. Differing
      injection procedures were employed such that rats were tested immediately after
      i.p. injection or 5 min after i.p. injection of 5 nmol/kg body wt of GRP. Results
      indicate that GRP does reduce the oral reinforcing properties of sucrose, but the
      effect is transient, diminishing significantly within 5 min after injection.

PMID- 12502520
TI  - Oral shear stress predicts flavour perception in viscous solutions.
AB  - The perception of sweetness and flavour were studied in viscous solutions
      containing 50 g/l sucrose, 100 p.p.m. iso-amyl acetate and varying concentrations
      of three hydrocolloid thickeners (guar gum, lambda-carrageenan and
      hydroxypropylmethyl cellulose). Zero-shear viscosity of the samples ranged from 1
      to 5000 mPas. Perception of both sweetness and aroma was suppressed at thickener
      concentrations above c* (coil overlap concentration, the point at which there is
      an abrupt increase in solution viscosity as thickener concentration is
      increased). Sensory data for the three hydrocolloids was only loosely correlated
      with their concentration relative to c* (c/c* ratio), particularly above c*.
      However, when perceptual data were plotted against the Kokini oral shear stress
      (tau), calculated from rheological measurements, data for the three hydrocolloids
      aligned to form a master-curve, enabling the prediction of flavour intensity in
      such systems. The fact that oral shear stress can be used to model sweetness and
      aroma perception supports the hypothesis that somatosensory tactile stimuli can
      interact with taste and aroma signals to modulate their perception.

PMID- 12502521
TI  - Detection thresholds for phenyl ethyl alcohol using serial dilutions in different
      solvents.
AB  - Detection thresholds are typically obtained by presenting a subject with serial
      dilutions of an odorant. Many factors, including the solvent used to dilute the
      odorant, can influence the measurement of detection thresholds. Differences have
      been reported in detection thresholds for phenyl ethyl alcohol (PEA) when
      different solvents are used. In this study we used gas chromatography (GC) to
      investigate further the effect of solvent on odor detection thresholds. We used a
      single ascending method and serial dilutions of PEA in four different solvents-
      liquid paraffin (LP), mineral oil (MO), propylene glycol (PG) and dipropylene
      glycol (DPG)--to determine the PEA thresholds for 31 adult subjects. For each
      solvent, we prepared eight serial log base 10 step dilutions (1-8), with
      corresponding liquid PEA concentrations of 6.3 x 10(1)-6.3 x 10(-6) (% v/v). We
      found that the threshold concentrations for PEA in LP (step 6.5) and PEA in MO
      (step 5.5) were significantly lower (P < 0.05) than for PEA in PG (step 4.0) and
      DPG (step 4.0) We then used GC to measure both the liquid and gas PEA
      concentrations for the dilution steps prepared with LP and PG. Although there
      were large threshold differences in the liquid concentrations of PEA in LP and
      PG, the headspace gas concentrations of PEA were the same. These results
      demonstrate the importance of determining the gas concentration of odorant
      stimuli when performing odor threshold measurements, in particular when comparing
      odor detection thresholds obtained using different solvents.

PMID- 12502522
TI  - The time course of taste bud regeneration after glossopharyngeal or greater
      superficial petrosal nerve transection in rats.
AB  - We previously have published data detailing the time course of taste bud
      regeneration in the anterior tongue following transection of the chorda tympani
      (CT) nerve in the rat. This study extends the prior work by determining the time
      course of taste bud regeneration in the vallate papilla, soft palate and
      nasoincisor ducts (NID) following transection of either the glossopharyngeal (GL)
      or greater superficial petrosal (GSP) nerve. Following GL transection in rats (n
      = 6 per time point), taste buds reappeared in the vallate papilla between 15 and
      28 days after surgery, and returned to 80.3% of control levels (n = 12) of taste
      buds by 70 days postsurgery. The first appearance and the final percentage of the
      normal complement of regenerated vallate taste buds after GL transection
      resembled that seen previously in the anterior tongue after CT transection.
      However, in the latter case, regenerated taste buds reached asymptotic levels by
      42 days after surgery, whereas within the time frame of the present study, a
      clear asymptotic return of vallate taste buds was not observed. In contrast to
      the posterior (and anterior) tongue, only 25% of the normal complement of palatal
      taste buds regenerated by 112 days and 224 days after GSP transection (n = 9).
      The difference in regenerative capacity might relate to the surgical approach
      used to transect the GSP. These experiments provide useful parametric data for
      investigators studying the functional consequences of gustatory nerve transection
      and regeneration.

PMID- 12502523
TI  - Stimulation of bitterness by capsaicin and menthol: differences between lingual
      areas innervated by the glossopharyngeal and chorda tympani nerves.
AB  - Capsaicin is viewed as a purely chemesthetic stimulus that selectively stimulates
      the somatosensory system. Here we show that when applied to small areas of the
      tongue, capsaicin can produce a bitter taste as well as sensory irritation. In
      experiment 1, individuals were screened for the ability to perceive bitterness
      from capsaicin on the circumvallate papillae. Fifteen of 25 subjects who reported
      at least weak bitterness rated the intensity of taste, irritation and coolness
      produced by 100-320 microM capsaicin and 100-320 mM menthol applied via cotton
      swabs to the tip (fungiform region), the posterior edge (foliate region), and the
      dorsal posterior surface (circumvallate region) of the tongue. Sucrose, citric
      acid, sodium chloride and quinine hydrochloride were applied to the same areas to
      assess tastes responsiveness. On average, capsaicin and menthol produced
      "moderate" bitterness (and no other significant taste qualities) in the
      circumvallate region, and weaker bitterness on the side and tip of the tongue.
      Sensory irritation from capsaicin was rated significantly higher at the tongue
      tip, whereas menthol coolness was rated higher in the circumvallate region. In
      experiment 2 we applied sucrose and quinine hydrochloride together with capsaicin
      to investigate the effects other taste stimuli might have on capsaicin's reported
      bitterness. As expected, adding quinine produced stronger bitterness in the
      circumvallate and fungiform regions, and adding sucrose significantly reduced the
      bitterness of capsaicin in the circumvallate region. Overall, the results suggest
      that capsaicin and menthol are capable of stimulating a subset of taste neurons
      that respond to bitter substances, perhaps via receptor-gated ion channels like
      those recently found in capsaicin- and menthol-sensitive trigeminal ganglion
      neurons, and that the glossopharyngeal nerve may contain more such neurons than
      the chorda tympani nerve. That some people fail to perceive bitterness from
      capsaicin further implies that the incidence of capsaicin-sensitive taste neurons
      varies across people as well as between gustatory nerves.

PMID- 12502524
TI  - Relationship between molecular structure, concentration and odor qualities of
      oxygenated aliphatic molecules.
AB  - Increasing the concentration of an odorant increases the number of receptor cells
      and glomeruli in the olfactory bulb that are stimulated, and it is commonly
      acknowledged that these represent increased numbers of receptor types. Currently,
      it is not known whether a receptor type is associated with a unique quality and a
      unique molecular feature of an odorant, or its activation is used by the brain in
      a combinatorial manner with other activated receptor types to produce a
      characteristic quality. The present study investigated the proposal that a
      molecular feature common to several aliphatic odorants and known to be the key
      feature required to stimulate the same mitral cells in the olfactory bulb results
      in a quality that is common to the odorants. Since the common structural feature
      may activate a specific receptor type possibly at a similar concentration, the
      qualities of the odorants were determined at seven concentrations where the
      lowest and highest concentrations were the detection threshold (DT) and 729DT of
      each subject. A list of 146 descriptors was used by 15 subjects to describe the
      qualities of each odorant at each concentration. The results indicate that each
      of the five odorants was characterized by different qualities and the qualities
      of four of the odorants changed with changes in concentration. Importantly, no
      quality common to each of the odorants that had the same molecular feature could
      be identified and it is proposed that identification of the odorants occurs via a
      combinatorial mechanism involving several types of receptors.

PMID- 12502528
TI  - The Na+/Ca2+ exchange molecule: an overview.
AB  - An overview of the molecular physiology of the Na(+)/Ca(2+) exchanger is
      presented. This includes information on the variety of exchangers that have been
      described and their regulatory properties. Molecular insight is most detailed for
      the cardiac Na(+)/Ca(2+) exchanger (NCX1). Parts of the NCS1 molecule involved in
      regulation and ion transport have been elucidated, and initial information on the
      topology and structure is available.

PMID- 12502529
TI  - Toward a topological model of the NCX1 exchanger.
AB  - The Na(+)/Ca(2+) exchanger (NCX1) catalyzes the counter-transport of sodium and
      calcium ions. Understanding how this is accomplished requires knowledge of the
      structure of NCX1 and identifying amino acid residues involved in binding and
      transport of ions. The amino acid sequence of NCX1 has been known for more than a
      decade. Based on hydropathy analysis, NCX1 was modeled to contain 12
      transmembrane segments. In this model, the alpha-repeat regions, which are the
      result of a gene duplication event (see below), are oriented on the extracellular
      face of NCX1. In the years since NCX1 was sequenced, a considerable amount of
      effort has gone into testing the initial 12-transmembrane-segment model.
      Immunologic and protein-processing studies as well as functional analyses of
      mutants have determined the location of the amino and carboxy termini and several
      intracellular regions. However, disulfide bond analysis and cysteine mutagenesis
      coupled with accessibility studies indicate that the structure of NCX1 diverges
      from a simple membrane protein consisting only of transmembrane alpha-helical
      segments. These recent data support a model containing 9 transmembrane alpha
      helices with the alpha-repeat regions forming nonhelical re-entrant loops. A
      bacterial protein containing a pair of alpha-repeat regions but of unknown
      function has also been shown to have oppositely oriented alpha-repeats.

PMID- 12502530
TI  - Probing ion binding sites in the Na+/Ca2+ exchanger.
AB  - The membrane domain of the Na(+)/Ca(2+) exchanger (NCX) contains two conserved
      internal repeat sequences, designated the alpha-1 and alpha-2 repeats. We have
      studied the topological disposition of residues in the alpha repeats and a
      neighboring region by substituted cysteine accessibility scanning as well as the
      functional importance of these residues by kinetically evaluating transport
      activities of cysteine-substituted or other site-directed NCX1 mutants. The
      results suggest that the alpha-1 repeat contains a reentrant loop originating
      from extracellular side of the membrane, while the alpha-2 repeat and its
      neighboring region contain a complex reentrant loop structure originating from
      the cytoplasmic side. We identified several residues in the alpha-1 repeat loop
      whose mutation caused significant alterations in the interaction of NCX1 with a
      transport substrate Ca(2+)(o) and inhibitory ions Ni(2+) and Co(2+). On the other
      hand, we found residues in the alpha-2 repeat loop region whose mutation altered
      the interaction with an activating ion Li(+) and an inhibitory drug KB-R7943 in
      addition to the effect on Ca(2+)(o) and Ni(2+). Collectively, our data suggest
      that these alpha-repeat regions participate in the formation of ion translocation
      pathway of the exchanger and that the alpha-1 repeat loop plays an important role
      in ion selection.

PMID- 12502531
TI  - Ion channel-like properties of the Na+/K+ Pump.
AB  - Ion pumps and exchangers are considered to be different from ion channels for two
      principal reasons. Ion pumps move ions against, whereas ion channels allow ions
      to move with, the electrochemical potential gradient, and pumps transport ions
      relatively slowly, approximately 10(2) s(-1), whereas channels conduct ions
      rapidly, approximately 10(7) s(-1). However, the latter high rate refers only to
      the open pore, and yet all ion channels contain at least one gate. Not
      surprisingly, the conformational changes associated with channel gating occur
      with kinetics similar to those of ion pumping. Indeed, ion pumps may be viewed as
      ion channels with two gates, one external to, and the other internal to, the ion
      binding cavity. The simple operational rule for such a pump is that the two gates
      should never be open simultaneously; otherwise, the pump would become a channel
      and conduct dissipative fluxes several orders of magnitude larger than, and in
      the opposite direction to, the active transport fluxes. Analyses of Na(+) ion
      movements mediated by the Na(+)/K(+) pump under various conditions have suggested
      that in at least one, short-lived, conformation of the pump, an ion-channel-like
      structure, closed at its intracellular end, connects the extracellular solution
      with the ion binding sites deep in the protein core. Here we use the marine
      toxin, palytoxin, to act on Na(+)/K(+) pumps in outside-out patches excised from
      cardiac myocytes and so transform the pumps into nonselective cation channels
      which we study using macroscopic, and single-channel, recording. We find that
      gating of the palytoxin-induced channels is regulated by the pump's natural
      ligands. Thus, external K(+) congeners tend to close, and external Na(+) tends to
      open, an extracellular gate, whereas ATP acts from the cytoplasmic solution to
      open an intracellular gate. These gating influences echo the normal ion occlusion
      and deocclusion reactions that first entrap two extracellular K(+) ions within
      the interior of the pump (between the two gates) and then release them to the
      cytoplasmic side in a step accelerated by ATP. These results offer the promise of
      being able to examine ion occlusion and deocclusion steps at the microscopic
      level in single Na(+)/K(+) pump molecules.

PMID- 12502532
TI  - The Na/Ca-K exchanger gene family.
AB  - Ca(2+) extrusion driven by both the inward Na(+) gradient as well as the outward
      K(+) gradient is essential for visual transduction in retinal rod and cone
      photoreceptors because it removes Ca(2+) that enters photoreceptors via the cGMP
      gated and light-sensitive channels. We have cloned rod and cone Na/Ca-K exchanger
      (NCKX) cDNAs from several species, and we have cloned NCKX cDNAs from lower
      organisms that lack vertebrate-type vision. Although in situ NCKX physiology has
      only been documented for vertebrate photoreceptors, it is now clear that NCKX
      gene products have a much broader distribution pattern. Here, we review some of
      the structural and functional features that have emerged from our studies on
      different members of the NCKX gene family.

PMID- 12502533
TI  - Toward comparative genomics of calcium transporters.

PMID- 12502534
TI  - Sodium-calcium exchanger NCX1, NCX2, and NCX3 transcripts in developing rat
      brain.

PMID- 12502535
TI  - Differential expression of Na/Ca exchanger and Na/Ca + K exchanger transcripts in
      rat brain.

PMID- 12502536
TI  - Sodium-calcium exchangers in olfactory tissue.

PMID- 12502537
TI  - Molecular identification of the NCX isoform expressed in tracheal smooth muscle
      of guinea pig.

PMID- 12502538
TI  - Localization and molecular characterization of the crayfish NCX.

PMID- 12502539
TI  - Characterization and functional activity of a truncated Na/Ca exchange isoform
      resulting from a new splicing pattern of NCX1.

PMID- 12502540
TI  - Activation of the cardiac Na+/Ca2+ exchanger by DEPC.

PMID- 12502542
TI  - Topological studies of the rat brain K+-dependent Na+/Ca2+ exchanger NCKX2.

PMID- 12502543
TI  - Studies on the oligomeric state of the sodium/calcium + potassium exchanger
      NCKX2.

PMID- 12502544
TI  - Conformational changes of the 120-kDa Na+/Ca2+ exchanger protein upon ligand
      binding: a Fourier transform infrared spectroscopy study.

PMID- 12502545
TI  - Sodium-calcium exchange crystallization.

PMID- 12502546
TI  - Proteomics approach to Na+/Ca2 exchangers in prokaryotes.

PMID- 12502547
TI  - Temperature dependence of cardiac Na+/Ca2+ exchanger.

PMID- 12502548
TI  - The Ca/Ca exchange mode of the Na/Ca exchanger investigated by photolytic Ca2+
      concentration jumps.

PMID- 12502549
TI  - Functional analysis of polar residues important for activity of Na+/H+
      exchangers.

PMID- 12502550
TI  - Stoichiometry of the Na+/Ca2+ exchanger: models and implications.
AB  - We reevaluated the exchange stoichiometry of the Na(+)/Ca(2+) exchange current by
      measuring its reversal potential. The exchange current was measured from the
      inside-out macropatch excised from intact sarcolemma of guinea pig ventricular
      myocytes. This method provides more accurate control of extracellular and
      cytoplasmic ion concentrations and of membrane potential than is possible with a
      whole-cell clamped preparation. The exchange current was isolated as exchanger
      inhibitory peptide (XIP)-sensitive current or as cytoplasmic Na(+)- and Ca(2+)
      induced current. The reversal potential of the Na(+)/Ca(2+) exchange current was,
      for the most part, close to the equilibrium potential of the 4Na(+):1Ca(2+)
      exchange, although it tended to get closer to that of 3Na(+): 1Ca(2+) exchange at
      lower Na(+) concentrations. We concluded that the stoichiometry is 4 or that it
      may vary depending on the cytoplasmic Na(+). The 4Na(+):1Ca(2+) exchange was
      further studied with computer modeling. A consecutive 4Na(+):1Ca(2+) exchange
      model with two active states and two inactive states (E2 model) could not well
      reconstruct the current-voltage relation of the exchanger. However, a consecutive
      4Na(+):1Ca(2+) exchange model with 10 active states and 2 inactive states (E10
      model), which included voltage-dependent Na(+) and Ca(2+) occlusions, well
      simulated the current-voltage relation. Implications of 4Na(+):1Ca(2+) exchange
      is also discussed.

PMID- 12502551
TI  - Influence of Na/Ca exchange stoichiometry on model cardiac action potentials.
AB  - Cardiac action potential simulations were done with the stoichiometry of the
      Na/Ca exchanger set a 4: 1. Using the Hilgemann-Noble (1987) model, this
      stoichiometry reduces the resting potential unless regulation by intracellular
      calcium is incorporated. The K(d) required for such regulation is consistent with
      current experimental estimates of this parameter.

PMID- 12502552
TI  - Rat heart NCX1.1 stoichiometry measured in a transfected cell system.
AB  - Expression of cDNA encoding the rat heart NCX1.1 protein in HEK-293 cells
      provides a simple system in which properties of the expressed protein can be
      determined in the absence of contaminating ionic conductances or parallel
      transport pathways. Using this system, we have determined that NCX1.1 transports
      4 Na(+) in exchange for 1 Ca(2+) and accompanied by the movement of 2 positive
      charges. The measured stoichiometry is constant over a range of different
      intracellular Na(+) and Ca(2+) concentrations, independent of the nature of the
      Ca(2+) buffer used and not affected by the direction of the applied voltage ramp.
      We conclude that our measurements are unlikely to be confounded by poor control
      over ionic conditions close to the intracellular surface of the membrane. A
      stoichiometry of 4:1 for NCX1 has important implications for models of the role
      of NCX1 in cellular Ca(2+) handling and suggests that in the heart the exchanger
      will be cardioprotective over a wider range of conditions and have a greater
      contribution to action potential shape than previously appreciated.

PMID- 12502553
TI  - Sodium-calcium exchange stoichiometry: is the noose tightening?
AB  - The stoichiometry of cardiac sodium-calcium exchange is of profound importance to
      understanding its physiological function, and recent work challenges a simple 3
      to-1 stoichiometry. We present a refined 3-to-1 exchange model that can explain
      recently measured reversal potentials that are close to those expected for a 4-to
      1 exchanger. The model assumes that 1 calcium and 1 sodium ion can be transported
      by the exchanger, albeit more slowly than 3 sodium ions or 1 calcium ion. In this
      model, currents and calcium fluxes reverse at different potentials; resting free
      calcium would always be higher than expected for a perfect 3-to-1 exchange
      process. To test models such as this, we have developed new methods to study ion
      transport processes in giant membrane patches independent of, or in parallel
      with, current measurements. Briefly, ion-selective electrodes or fluorescent ion
      indicators are used to detect concentration changes in the pipette, close to the
      membrane, upon activation of transport activity. Preliminary results are
      presented.

PMID- 12502555
TI  - Reexamination of the stoichiometry of Na+/Ca2+ exchange with whole-cell voltage
      clamp of guinea pig ventricular myocytes.

PMID- 12502556
TI  - Simultaneous measurement of [Na]i, [Ca]i, and I(NCX) in intact cardiac myocytes.

PMID- 12502557
TI  - Electrophysiological studies of the cloned rat cardiac NCX1.1 in transfected HEK
      cells: a focus on the stoichiometry.

PMID- 12502558
TI  - Tissue-specific modes of Na/Ca exchanger regulation.
AB  - Ionic regulation of Na(+)/Ca(2+) exchange describes the secondary modulating
      effects exerted on exchange activity by the transport substrates Na(+) and
      Ca(2+). These effects have been extensively characterized for the cardiac
      Na(+)/Ca(2+) exchanger, NCX1.1, primarily by the giant excised patch-clamp
      technique. Moreover, several studies have provided functional evidence for ionic
      regulation of Na(+)/Ca(2+) exchange activity in intact cellular systems. Through
      structure-function analyses, important protein domains involved in these
      regulatory processes have been identified. However, despite major progress in
      characterizing ionic regulation at the functional and molecular levels, the
      physiological importance of these processes remains unknown. In this study, we
      have examined Na(+)/Ca(2+) exchange activity for three members of the NCX1
      family, namely NCX1.1, NCX1.3, and NCX1.4. These exchangers were expressed in
      Xenopus laevis oocytes and were characterized using the giant excised patch-clamp
      technique. We show that these three splice variants exhibit considerable
      differences in the kinetic features of their ionic regulatory profiles.
      Information of this type is beginning to provide insight into the physiological
      basis for tissue-specific expression of alternatively spliced Na(+)/Ca(2+)
      exchangers.

PMID- 12502559
TI  - NCX1 surface expression: a tool to identify structural elements of functional
      importance.
AB  - The rat Na(+)/Ca(2+) exchanger isoforms of the NCX1 gene have 14 cysteine
      residues. Each of these cysteines can be mutated individually to alanine or
      serine without loss of functional expression in transfected HEK293 cells. Yet
      sequential exchange starting from the amino terminal end of three or more
      cysteines results in reduced transport activity and surface expression. As more
      and more cysteines are replaced, transport activity and surface expression
      decrease in parallel, and the cysteineless mutant exhibits only traces of
      Na(+)/Ca(2+) exchange activity and surface expression. No significant differences
      are detected in the amount of total cell exchanger protein between the wild-type
      exchanger and its functional or nonfunctional cysteine mutants. Reduced surface
      expression of the Na(+)/Ca(2+) exchanger NCX1 is also observed when HEK293 cells
      expressing the transporter are treated with cyclosporin A (CsA) or with PSC833.
      The reductions in transport activity and surface expression are concentration
      dependent and parallel. No reduction is obtained in the total amount of exchanger
      protein by CsA or PSC833 treatment, suggesting that the effects of these drugs on
      NCX1 expression are posttranslational. FK506 and rapamycin treatment of HEK293
      cells expressing rat NCX1 isoforms has no effect on transport activity, surface
      expression, or the total amount of exchanger protein in the transfected cells.

PMID- 12502560
TI  - Functional regulation of alternatively spliced Na+/Ca2+ exchanger (NCX1)
      isoforms.
AB  - Alternative splicing of RNA transcripts is a general characteristic for NCX genes
      in mammals, mollusks, and arthropods. Among the family of three NCX genes in
      mammals, the NCX1 gene contains six exons, namely, A, B, C, D, E, and F, that
      make up the alternatively spliced region. Studies of the NCX1 gene transcripts
      suggested that 16 distinct gene products can be produced from the NCX1 gene. The
      exons A and B are mutually exclusive when expressed. Generally, exon A-containing
      transcripts are predominantly found in excitable cells like cardiomyoctes and
      neurons, whereas exon B-containing transcripts are mostly found in nonexcitable
      cells like astrocytes and kidney cells. Other alternatively spliced exons (C-F)
      appear to be cassette-type exons and are found in various combinations.
      Interestingly, exon D is present in all characterized transcripts. The
      alternatively spliced isoforms of NCX1 show tissue-specific expression patterns,
      suggesting functional adaptation to tissues. To investigate functional
      differences among alternatively spliced isoforms of NCX1, we expressed an exon A
      containing transcript present in cardiac tissue (NCX1.1) and an exon B-containing
      transcript found in the kidney (NCX1.3) in Xenopus oocytes. We demonstrated that
      the Na(+)/Ca(2+) exchangers expressed by exon A- and exon B-containing
      transcripts display differences in activation by PKA and by [Ca(2+)](i). We also
      observed that these two isoforms show differences in voltage dependence.
      Surprisingly, the alternatively spliced isoforms of NCX1 display greater
      functional differences among themselves than the products of different gene loci,
      NCX1, NCX2, and NCX3.

PMID- 12502561
TI  - The cardiac sodium-calcium exchanger associates with caveolin-3.
AB  - The cardiac Na/Ca exchanger's (NCX1) role in calcium homeostasis during
      myocardial contractility makes it a possible target of signaling factors
      regulating inotropy. Caveolae, structured invaginations of the plasmalemma, are
      known to concentrate a wide variety of signaling factors. The predominant coat
      proteins of caveolae, caveolins, dock to and regulate the activity of these
      signaling factors and other proteins through interaction with their scaffolding
      domain. In this study we investigated the interaction of NCX1 with caveolin
      proteins. Western blots of bovine cardiac sarcolemmal vesicles revealed the
      presence of caveolin-1, -2, and -3. Immunoprecipitation of detergent-solubilized
      vesicle proteins with either NCX1 or caveolin-3 antibodies indicated that NCX1
      coprecipitates with caveolin-3, but not with caveolin-1 and -2. Functional
      disruption of caveolae, by beta-cyclodextrin treatment of vesicles, diminished
      coprecipitation of caveolin-3 and NCX1 activity. NCX1 has five potential caveolin
      binding motifs, two of which are in the transporter's exchange inhibitory peptide
      (XIP) domain. The presence of 50 mM XIP peptide enhanced coprecipitation of
      caveolin-3 with NCX1 independent of calcium concentration. We conclude that NCX1
      associates specifically with caveolin-3. Partitioning of NCX1 in caveolae has
      implications for temporal and spatial regulation of excitation-contraction and 
      relaxation coupling in cardiac myocytes.

PMID- 12502562
TI  - Kinetic model of transport and regulation of the cardiac, brain, and kidney
      isoforms of NCX1.

PMID- 12502563
TI  - Phosphorylation of the Na+/Ca2) exchangers by PKA.

PMID- 12502564
TI  - Cellular regulation of sodium-calcium exchange.
AB  - Na(+)/Ca(2+) exchange activity was studied in transfected Chinese hamster ovary
      (CHO) cells expressing the wild-type cardiac exchanger (NCX1.1) or mutants
      created by site-directed mutagenesis. The activity of the wild-type exchanger,
      but not exchanger mutants deficient in Ca(2+)-dependent activation, was inhibited
      by sphingolipids such as ceramide and sphingosine. We propose that sphingolipids
      interfere with the regulatory activation of exchange activity by Ca(2+) and
      suggest that this interaction provides a means for monitoring and regulating
      diastolic Ca(2+) levels in beating cardiac myocytes. Exchange activity in CHO
      cells was also linked, through a poorly understood feedback mechanism, to Ca(2+)
      accumulation within internal stores such as the endoplasmic reticulum and the
      mitochondria. Finally, the F-actin cytoskeleton was shown to modulate exchange
      activity through interactions involving the exchanger's central hydrophilic
      domain. We conclude that regulation of exchange activity in intact cells involves
      multiple interactions with various lipid species, cytosolic Ca(2+), organellar
      Ca(2+) stores, and the cytoskeleton.

PMID- 12502565
TI  - Intracellular ionic and metabolic regulation of squid nerve Na+/Ca2+ exchanger.
AB  - Intracellular Na(+) and H(+) synergistically inhibit the squid Na(+)/Ca(2+)
      exchanger by reducing the affinity for Ca(2+) of its regulatory site. MgATP
      antagonizes H(+)(i) and Na(+)(i) inhibition; this effect must occur through a
      phosphorylation-dephosphorylation process, because exogenous protein phosphatases
      prevent MgATP activation of the exchanger. Protection by ATP against H(+)(i) and
      Na(+)(i) inhibition happens by decreasing the apparent affinity for the
      synergistic binding of these cations to the carrier. In this way ATP modifies the
      apparent affinity for Ca(2+) of its regulatory site. Mg(2+) ions play an
      important role in the process because they are essential for ATP activation of
      Na(+)/Ca(2+) exchange but can also promote deactivation of the ATP upregulated
      exchanger. At constant [ATP], activation at low [Mg(2+)](i) is followed by
      deactivation as [Mg(2+)](i) is increased. The most likely explanation for
      deactivation is stimulation of endogenous phosphatases. We developed a kinetic
      model that predicts all H(+)(i), Na(+)(i), and MgATP described above. This scheme
      includes the following conditions: (i) The binding of Ca(2+) to the regulatory
      site is essential for the binding of Na(+)(i) or Ca(2+)(i) to the transporting
      sites. (ii) The binding of a first H(+)(i) to the carrier displaces Ca(2+)(i)
      from its regulatory site and allows binding of one Na(+) forming a H.E(1).Na
      complex. The H.E(1).Na complex can bind a second H(+)(i) forming a dead-end
      inhibitory H(2).E(1).Na complex. (iii) MgATP, through an unspecified
      phosphorylation process, decreases the apparent affinity for the synergistic
      H(+)(i) and Na(+)(i) binding to the carrier.

PMID- 12502566
TI  - Pathways regulating Na+/Ca2+ exchanger expression in the heart.
AB  - The Na(+)/Ca(2+) exchanger (NCX1) is regulated at the transcriptional level in
      cardiac hypertrophy, ischemia, and failure. Following pressure overload,
      activation of MAPKs coincides with the kinetics of NCX1 gene upregulation in
      adult cardiocytes. Using adenoviral gene delivery, we begin to identify the
      molecular pathways responsible for upregulation of the exchanger gene. Inhibition
      of ERK with the MEK inhibitor UO126, the ERK protein phosphatase MKP-3, inhibited
      ERK activation, but only inhibited alpha-adrenergic-induced NCX1 upregulation by
      30%. Overexpression of DN-JNK lowered basal NCX1 expression. Overexpression of
      activated MKK-3 was sufficient for alpha-adrenergic-stimulated upregulation of
      the reporter gene. Together, this data indicates that (1) JNK mediates basal
      cardiac expression of the NCX1 gene, (2) ERK and p38 play a role in alpha
      adrenergic-stimulated NCX1 upregulation, and (3) p38 activation alone is
      sufficient for NCX1 upregulation.

PMID- 12502567
TI  - Multiple modes of regulation of Na+/H+ exchangers.
AB  - Mammalian Na(+)/H(+) exchangers (NHE) mediate electroneutral countertransport of
      H(+) for Na(+) across the plasmalemmal and organellar membranes. They contribute
      to cellular and organellar pH and volume regulation and transepithelial Na(+)
      transport. The aim of this review is to illustrate the complex regulation of
      these transporters by focusing on the multiple mechanisms controlling the
      epithelial isoform, NHE3. A variety of agents and conditions (e.g., hormones,
      growth factors, cellular pH, and medium osmolarity) act in concert to achieve
      short-term and long-term regulation of this isoform. The underlying mechanism
      involves changes in the number of transporters on the cell surface and/or altered
      activity of the individual exchangers due to allosteric activation by
      intracellular protons, phosphorylation and interaction with accessory proteins
      and the cytoskeleton. A similar regulatory versatility probably applies to other
      NHE isoforms, and the lessons learned from studying members of the NHE family
      could serve as a useful reference when exploring the modes and levels of
      regulation of other transporters.

PMID- 12502568
TI  - Cyclosporin A regulates sodium-calcium exchanger (NCX1) gene expression in vitro
      and cardiac hypertrophy in NCX1 transgenic mice.
AB  - The cardiac-specific sodium-calcium exchanger (NCX1) is a GATA-4 dependent gene
      that is upregulated during cardiac hypertrophy and heart failure. To date, lack
      of an appropriate inhibitor of NCX1 and embryonic lethality of NCX1 knockout mice
      have slowed investigation of the relation between NCX1 upregulation and cardiac
      hypertrophy. Recently, in vitro studies have shown that cyclosporin A (CSA), a
      calcineurin inhibitor, significantly downregulated expression of the hypertrophic
      genes atrial natriuretic factor and beta-myosin heavy chain and protected against
      cardiac hypertrophy and heart failure in calcineurin overexpressing mice. This
      suggested that CSA might play an important role in the treatment of hypertrophy
      and heart failure. In an in vitro model of cardiac hypertrophy, we showed that
      CSA is a potent inhibitor of NCX1 basal expression and NCX1 promoter activity.
      Female homozygous transgenic mice that overexpress NCX1 develop heart failure and
      die prematurely after two or more pregnancies. Others have demonstrated that
      pressure overloaded wild-type mice treated with CSA do not develop cardiac
      hypertrophy and downregulate expression of NCX1. We investigated the effect of
      CSA on NCX1 expression and transverse aortic constriction-induced cardiac
      hypertrophy in NCX1 overexpressing mice. We found that CSA blunted these
      responses.

PMID- 12502569
TI  - Role of sodium-calcium exchanger (Ncx1) in embryonic heart development: a
      transgenic rescue?
AB  - Na(+)/Ca(2+) exchanger (Ncx-1) is highly expressed in cardiomyocytes, is thought
      to be required to maintain a low intracellular Ca(2+) concentration, and may play
      a role in excitation-contraction coupling. Significantly, targeted deletion of
      Ncx-1 results in Ncx1-null embryos that do not have a spontaneously beating heart
      and die in utero. Ultrastructural analysis revealed gross anomalies in the Ncx1
      null contractile apparatus, but physiologic analysis showed normal field
      stimulated Ca(2+) transients, suggesting that Ncx-1 function may not be critical
      for Ca(2+) extrusion from the cytosol as previously thought. Using caffeine to
      empty the intracellular Ca(2+) stores, we show that the sarcoplasmic reticulum is
      not fully functional within the 9.5-dpc mouse heart, indicating that the
      sarcoplasmic reticulum is unlikely to account for the unexpected maintenance of
      intracellular Ca(2+) homeostasis. Using the Ncx1-lacZ reporter, our data indicate
      restricted expression patterns of Ncx1 and that Ncx1 is highly expressed within
      the conduction system, suggesting Ncx1 may be required for spontaneous pacemaking
      activity. To test this hypothesis, we used transgenic mice overexpressing one of
      the two known adult Ncx1 isoforms under the control of the cardiac-specific a
      myosin heavy chain promoter to restore Ncx1 expression within the Ncx1-null
      hearts. Results indicate that the transgenic re-expression of one Ncx1 isoform
      was unable to rescue the lethal null mutant phenotype. Furthermore, our in situ
      results indicate that both known adult Ncx1 isoforms are coexpressed within the
      embryonic heart, suggesting that effective transgenic rescue may require the
      presence of both isoforms within the developing heart.

PMID- 12502570
TI  - The gene promoter of human Na+/Ca2+ exchanger isoform 3 (SLC8A3) is controlled by
      cAMP and calcium.

PMID- 12502571
TI  - Role of MAP kinases in the Na+/Ca2+ exchanger gene expression in feline adult
      cardiocytes.

PMID- 12502572
TI  - Regulation of phosphatidylinositol-4,5-biphosphate bound to the bovine cardiac
      Na+/Ca2+ exchanger.
AB  - Western blot and cross immunoprecipitation analysis with specific antibodies
      demonstrate that in bovine heart sarcolemmal vesicles phosphatidylinositol-4,5
      biphosphate (PtdIns-4,5-P(2)) binds strongly to the Na(+)/Ca(2+) exchanger
      (NCX1). This binding is modulated by ATP, Ca(2+), vanadate, exchanger inhibitory
      peptide (XIP), and PLC-PtdIns specific in a way resembling the ATP regulation of
      the exchange fluxes. With 1 microM Ca(2+), 3 mM Mg(2+), and 0.4 mM vanadate, 1 mM
      ATP increased about twofold the bound PtdIns-4,5-P(2), reaching a steady state in
      3-5 s at 37 degrees C. With 100 microM Ca(2+), ATP had no effect on the PtdIns
      4,5-P(2) bound to NCX1 or on the exchange fluxes. Without vanadate the bound
      PtdIns-4,5-P(2) was largely reduced; under this condition ATP failed to increase
      it and did not stimulate the exchanger. XIP inhibits the exchanger, more
      noticeable in the absence of ATP. With XIP, ATP does not modify the levels of
      bound PtdIns-4,5-P(2); however there is a small but distinct ATP stimulation of
      the exchanger. Vesicles pretreated with PtdIns-PLC, showed no de novo, [(32)P]ATP
      induced, production of PtdIns-4,5-P(2), but some ATP-stimulated increase in the
      bound PtdIns-4,5-P(2) was detected; however, that increase did not exceed the
      levels found with vanadate and no ATP. These results indicate that in bovine
      heart sarcolemmal vesicles, ATP upregulation of NCX1 is related to PtdIns-4,5
      P(2) bound to the exchanger, perhaps over a "threshold" or "unspecific" amount.
      In addition, vanadate could influence the amount of detected PtdIns-4,5-P(2)
      either by inhibiting phosphoinositide-specific phosphatases and/or by inducing a
      redistribution of PtdIns-4,5-P(2) molecules associated with the Na(+)/Ca(2+)
      exchanger.

PMID- 12502573
TI  - Potassium-dependent sodium-calcium exchange through the eye of the fly.
AB  - In this review, we describe the characterization of a Drosophila sodium/calcium
      potassium exchanger, Nckx30C. Sodium/calcium (-potassium) exchangers (NCX and
      NCKX) are required for the rapid removal of calcium in excitable cells. The
      deduced protein topology for NCKX30C is similar to that of mammalian NCKX, with 5
      hydrophobic domains in the amino terminus separated from 6 at the carboxy
      terminal end by a large intracellular loop. NCKX30C functions as a potassium
      dependent sodium-calcium exchanger and is expressed in adult neurons and during
      ventral nerve cord development in the embryo. Nckx30C is expressed in a
      dorsal/ventral pattern in the eye-antennal disc, suggesting that large fluxes of
      calcium may be occurring during imaginal disc development in the larvae. NCKX30C
      may play a critical role in modulating calcium during development as well as in
      the removal of calcium and maintenance of calcium homeostasis in adults.

PMID- 12502574
TI  - Na/Ca exchange in function, growth, and demise of beta-cells.
AB  - Recent knowledge concerning the Na/Ca exchanger (NCX) in the pancreatic beta-cell
      is reviewed. The beta-cell expresses various NCX1 splice variants in a species
      specific pattern (NCX1.3 and 1.7 in the rat; NCX1.2, 1.3, and 1.7 in the mouse)
      and in variable and different proportions. In the rat beta-cell, the exchanger
      displays a high capacity, accounts for about 70% of Ca(2+) extrusion, and
      participates in Ca(2+) inflow during membrane depolarization. In the mouse,
      however, the contribution of the exchanger to Ca(2+) extrusion is more modest,
      and to Ca(2+) inflow, less evident. The exchanger has a stoichiometry of 3 Na(+)
      for 1 Ca(2+), is electrogenic, and displays a reversal potential at -20 mV.
      Although being of low magnitude, the current generated by the exchanger shapes
      glucose-induced beta-cell electrical activity and intracellular Ca(2+)
      oscillations. Intracellular Ca(2+) may also trigger apoptosis. For instance,
      overexpression of the exchanger increases Ca(2+)-dependent and Ca(2+)-independent
      beta-cell death by apoptosis, a phenomenon resulting from the depletion of ER
      Ca(2+) stores with subsequent activation of caspase-12. Na/Ca exchange
      overexpression also reduces beta-cell growth. Hence, the Na/Ca exchanger is a
      versatile system that appears to play an important role in the function, growth,
      and demise of the beta-cell.

PMID- 12502575
TI  - Binding of the retinal rod Na+/Ca2+-K+ exchanger to the cGMP-gated channel
      indicates local Ca(2+)-signaling in vertebrate photoreceptors.
AB  - Ca(2+) ions enter the outer segment of rod or cone photoreceptors exclusively
      through the cGMP-gated channel and are extruded by the Na(+)/Ca(2+)-K(+)
      exchanger. Recent evidence indicates that in the plasma membrane, the
      Na(+)/Ca(2+)-K(+) exchanger is associated with the cGMP-gated channel. In this
      contribution, the possible physiologic significance of this protein complex is
      considered. Based on recent experimental evidence, the possibility of a direct
      functional interaction between the cGMP-gated channel and the Na(+)/Ca(2+)-K(+)
      exchanger is discussed. Furthermore, a quantitative estimation of the cytoplasmic
      Ca(2+) diffusion at the cGMP-gated channel indicates that Ca(2+) diffusion is
      largely confined to the complex of the cGMP-gated channel and the associated
      Na(+)/Ca(2+)-K(+) exchanger molecules.

PMID- 12502576
TI  - Exercise training enhances coronary smooth muscle cell sodium-calcium exchange
      activity in diabetic dyslipidemic Yucatan swine.

PMID- 12502577
TI  - Dysregulation of [Ca2+](i) in OK-PTH cells expressing a mesangial cell Na+/Ca2+
      exchanger isoform from Dahl/Rapp salt-sensitive rats.

PMID- 12502578
TI  - Enhanced susceptibility of a Na+/Ca2+ exchanger isoform from mesangial cells of
      salt-sensitive Dahl/Rapp rats to oxidative stress inactivation.

PMID- 12502579
TI  - Reverse mode Na+/Ca2+ exchange in the collagen activation of human platelets.

PMID- 12502580
TI  - Na+/Ca2+ exchange in activated and nonactivated human platelets.

PMID- 12502581
TI  - Effect of glucose on the expression level of the plasma membrane Ca2+-ATPase and
      the Na+/Ca2+ exchanger in pancreatic islet cells.

PMID- 12502582
TI  - Na/Ca exchanger and PMCA localization in neurons and astrocytes: functional
      implications.
AB  - Immunocytochemistry reveals that the Na/Ca exchanger (NCX) in neuronal somata and
      astrocytes is confined to plasma membrane (PM) microdomains that overlie sub-PM
      (junctional) endoplasmic reticulum (jER). By contrast, the PM Ca(2+) pump (PMCA)
      is more uniformly distributed in the PM. At presynaptic nerve terminals, the NCX
      distribution is consistent with that observed in the neuronal somata, but the
      PMCA is clustered at the active zones. Thus, the PMCA, with high affinity for
      Ca(2+) (K(d) congruent with 100 nM), may keep active zone Ca(2+) very low and
      thereby "reprime" the vesicular release mechanism following activity. NCX, with
      lower affinity for Ca(2+) (K(d) congruent with 1,000 nM), on the other hand, may
      extrude Ca(2+) that has diffused away from the active zones and been temporarily
      sequestered in the endoplasmic reticulum. The PL microdomains that contain the
      NCX also contain Na(+) pump high ouabain affinity alpha2 (astrocytes) or alpha 3
      (neurons) subunit isoforms (IC(50) congruent with 5-50 nM ouabain). In contrast,
      the alpha1 isoform (low ouabain affinity in rodents; IC(50) >10,000 nM), like the
      PMCA, is more uniformly distributed in these cells. The sub-PM endoplasmic
      reticulum in neurons (and probably glia and other cell types as well) and the
      adjacent PM form junctions that resemble cardiac muscle dyads. We suggest that
      the PM microdomains containing NCX and alpha 2/alpha 3 Na(+) pumps, the
      underlying jER, and the intervening tiny volume of cytosol (<10(-18) l) form
      functional units (PLasmERosomes); diffusion of Na(+) and Ca(2+) between these
      cytosolic compartments and "bulk" cytosol may be markedly restricted. The
      activity of the Na(+) pumps with alpha 2/alpha 3 subunits may thus regulate NCX
      activity and jER Ca(2+) content. This view is supported by studies in mice with
      genetically reduced (by congruent with 50%) alpha 2 Na(+) pumps: evoked Ca(2+)
      transients were augmented in these cells despite normal cytosolic Na(+) and
      resting Ca(2+) concentrations ([Na(+)](CYT) and [Ca(2+)](CYT)). We conclude that
      alpha 2/alpha 3 Na(+) pumps control PLasmERosome (local) [Na(+)](CYT). This, in
      turn, via NCX, modulates local [Ca(2+)](CYT), jER Ca(2+) storage, Ca(2+)
      signaling, and cell responses.

PMID- 12502583
TI  - Immunohistochemical detection of the sodium-calcium exchanger in rat hippocampus
      cultures using subtype-specific antibodies.
AB  - All of the known Na+/Ca2+ exchanger subtypes, NCX1-3, are expressed in the brain,
      albeit with marked regional differences. On the mRNA level, overall expression
      seems most prominent for NCX2, intermediate for NCX1, and, except for a few
      regions, low for NCX3. Using three subtype-specific antibodies, we have now
      studied the cellular expression of the NCX subtypes in rat hippocampus cultures
      by immunohistochemical techniques. Our results provide evidence for a highly cell
      specific expression pattern of NCX subtypes and show surprisingly little
      colocalization. NCX1 and NCX3 are both primarily expressed in neuronal cells.
      While NCX1 is found in the large majority of neurons, NCX3 expression was
      restricted to a small minority of cells. By contrast, NCX2 was almost exclusively
      present in glial cells. The NCX2 antibody, a IgM, stained glial cell membranes as
      well as an intermediate fibrillar system. In spite of extensive screening, the
      nature of this fiber system has not yet been identified.

PMID- 12502584
TI  - A study of the activity of the plasma membrane Na/Ca exchanger in the cellular
      environment.
AB  - The Na/Ca exchanger is a large-capacity system that is supposed to be predominant
      in the ejection of calcium in excitable tissues. Its activity is normally
      evaluated in electro-physiological experiments or using Na-loaded cells or plasma
      membrane vesicles in experiments in which the activity is estimated by measuring
      the uptake of isotopic calcium. Here the activity of the exchanger has been
      evaluated in model cells that coexpress the exchanger together with the (protein)
      Ca indicator aequorin targeted to the different subcellular compartments.
      Exchanger isoform 1 (NCX1) has been used for experiments in which the effect of
      its overexpression has been evaluated on the Ca homeostasis in the cytoplasm at
      large, in the endoplasmic reticulum, in mitochondria, and in the layer of
      cytoplasm underneath the plasma membrane. The experiments have shown that,
      despite its very low calcium affinity, the exchanger was active in cells at rest
      in which calcium is around 100 nM. They have also shown that expressed NCX1
      significantly reduced the cytosolic and mitochondrial calcium transients produced
      by the emptying of the ER calcium stores with InsP3-linked agonists. The effect
      of the expressed NCX1 on the calcium homeostasis in the domain underneath the
      plasma membrane was more complex: The exchanger apparently catalyzed a reverse
      operation, leading to increased penetration of calcium.

PMID- 12502585
TI  - K+-dependent Na+/Ca2+ exchangers in the brain.
AB  - Sodium-calcium exchange was first characterized in heart myocytes and squid axon
      more than 3 decades ago. Since then, it has been appreciated that functioning of
      the Na/Ca exchanger molecule plays a critical role in calcium homeostasis in
      neurons. Genome analysis indicates that Na/Ca exchangers are a superfamily
      encoded by 7 different genes divided into 2 groups: the Na/Ca exchangers (NCX;
      SLC8) and the Na/Ca+K exchangers (NCKX; SLC24). Two different NCX genes, NCX1 and
      NCX2, are highly expressed in brain. We recently described the widespread
      expression of 2 NCKX-type exchangers in brain, NCKX2 and NCKX3, and uncovered
      evidence for expression of another, NCKX4. The unique role that each different
      exchanger plays in neuronal calcium homeostasis, however, awaits further
      investigation. To begin exploring this central question, we examined both the
      expression pattern and the functional properties of the K-dependent Na/Ca
      exchanger isoforms expressed in brain and compared and contrasted these with NCX
      type exchangers. Distinct patterns of transcript abundance, regional
      distribution, and developmental expression were noted for each isoform.
      Functional properties, including stoichiometry and the kinetic characteristics of
      ion binding, were determined for NCKX2 and are discussed in the context of
      cellular Ca2+ signaling.

PMID- 12502586
TI  - Brain distribution of the Na+/Ca2+ exchanger-encoding genes NCX1, NCX2, and NCX3
      and their related proteins in the central nervous system.
AB  - In the central nervous system, the Na(+)/Ca(2+) exchanger plays a fundamental
      role in controlling changes in the intracellular concentrations of Na(+) and
      Ca(2+) ions that occur in physiologic conditions such as neurotransmitter
      release, cell migration and differentiation, gene expression, as well as neuro
      degenerative processes. Three genes, NCX1, NCX2, and NCX3, encoding for
      Na(+)/Ca(2+) exchanger isoforms have been cloned. In this review, by using non
      radioactive in situ hybridization and light immunohistochemistry with NCX isoform
      specific riboprobes and antibodies, respectively, a systematic brain mapping for
      both transcripts and proteins encoded by all three NCX genes is described.
      Intense expression of NCX transcripts and proteins was detected in the cerebral
      cortex, hippocampus, thalamus, metathalamus, hypothalamus, brainstem, spinal
      cord, and cerebellum. In these areas, NCX transcripts and proteins were often
      found with an overlapping distribution pattern, although specific brain areas
      displaying a peculiar expression of each exchanger isoform were also found.
      Furthermore, immunoelectron and confocal microscopy revealed the expression of
      the NCX1 isoform of the exchanger at both pre- and postsynaptic sites as well as
      in association with membranes of the endoplasmic reticulum. Collectively, these
      data suggest that the different isoforms of the Na(+)/Ca(2+) exchanger appear to
      be selectively expressed in several CNS regions where they might underlie
      different functional roles.

PMID- 12502587
TI  - Neurotransmitter-induced activation of sodium-calcium exchange causes neuronal
      excitation.

PMID- 12502588
TI  - Na+/Ca2+ exchanger in Na+ efflux-Ca2+ influx mode of operation exerts a
      neuroprotective role in cellular models of in vitro anoxia and in vivo cerebral
      ischemia.

PMID- 12502589
TI  - Mitochondria buffer sodium-dependent CA2+ influx in cultured cerebellar granule
      cells.

PMID- 12502590
TI  - ATP stimulation of Na+/Ca2+ exchanger in bovine brain membrane vesicles is
      similar to that of the heart and independent of ionic strength of assay or
      preparation.

PMID- 12502591
TI  - Is Na/Ca exchange during ischemia and reperfusion beneficial or detrimental?
AB  - Cytosolic calcium increases to approximately 3 micro M after 15 min of global
      ischemia. Manipulations that attenuate this increase in cytosolic Ca(2+) reduce
      myocyte death and dysfunction. The increase in cytosolic Ca(2+) during ischemia
      is dependent on an increase in intracellular Na(+), suggesting a role for Na/Ca
      exchange. Typical ischemic values for ionized intra- and extracellular Na(+),
      Ca(2+), and membrane potential are consistent with the Na/Ca exchanger operating
      near equilibrium during ischemia. Studies were undertaken using hearts from mice
      that overexpress the Na/Ca exchanger to determine if Na/Ca exchanger
      overexpression enhances or reduces ischemic injury. These studies suggest that
      overexpression of the Na/Ca exchanger enhances injury in males, but females are
      protected by a gender-related mechanism.

PMID- 12502592
TI  - Simulation of Na/Ca exchange activity during ischemia.
AB  - Simulation of sodium-calcium exchange activity during the rise of intracellular
      sodium that occurs during ischemia suggests that the exchanger may not reverse
      direction except transiently during calcium oscillations. This conclusion depends
      on the presence of a small resting leak of calcium into the cell, consistent with
      radioactive calcium flux measurements. The conditions for intracellular calcium
      to rise to around 3 microM were explored. A combination of extracellular
      potassium accumulation and extracellular sodium depletion is sufficient to
      explain this result. The computations also show a counterintuitive result
      concerning the role of the exchanger in the mechanism of calcium oscillations.
      Reducing its activity would be expected to enhance these oscillations, whereas
      increasing it can reduce or suppress oscillations. If such oscillations play a
      role in acute ischemic arrhythmias, then block of Na/Ca exchange may not be
      therapeutic.

PMID- 12502593
TI  - Role of the Na/Ca exchanger in arrhythmias in compensated hypertrophy.
AB  - Sudden, presumably arrhythmic, death is common in heart failure patients.
      Although total mortality is highest in end-stage failure, the fraction of sudden
      death in total mortality is higher in the early stages. In each of these stages
      various, not necessarily identical, ionic mechanisms may contribute to
      arrhythmogenesis. Dogs with chronic complete atrioventricular block (6-8 weeks)
      have an increased risk for arrhythmias and sudden death and have compensated
      biventricular hypertrophy. In this animal model, Ca(2+) release from the
      sarcoplasmic reticulum (SR) is not reduced. For low frequencies of stimulation,
      the SR Ca(2+) content is increased, related to a higher activity of the Na/Ca
      exchanger. Spontaneous Ca(2+) release induces inward Na/Ca exchange current,
      which can lead to delayed afterdepolarizations (DADs) triggering a new action
      potential. Such arrhythmogenic DADs and ectopic beats also can be observed in
      vivo during monophasic action potential recording. They appear after pacing
      protocols, and/or administration of ouabain, which result in contractile
      potentiation, suggestive of a enhanced sarcoplasmic reticulum Ca(2+) content.
      Other arrhythmogenic mechanisms related to increased dispersion of repolarization
      also can be identified in vivo. Downregulation of delayed K(+) currents is an
      important factor in prolongation of action potentials. In conclusion, in this
      animal model of compensated hypertrophy, Ca(2+) handling is different from end
      stage heart failure. It is possible that arrhythmogenic mechanisms related to a
      higher Ca(2+) load contribute to the high incidence of sudden death in stages of
      compensated hypertrophy before overt heart failure. However, more than one ionic
      remodeling process is likely to be present, and different cellular mechanisms of
      arrhythmias can coexist.

PMID- 12502594
TI  - Enhanced sodium-calcium exchange in the infarcted heart: effects on sarcoplasmic
      reticulum content and cellular contractility.
AB  - Arrhythmias and contractile dysfunction both contribute to the high morbidity and
      mortality in patients with congestive heart failure. Contractile dysfunction is
      generally believed to reflect a decrease in the amplitude of intracellular Ca(2+)
      transients, whereas tachyarrythmias are often initiated in the setting of
      cellular Ca(2+) overload. In a rabbit model of left ventricular dysfunction due
      to myocardial infarction, we found evidence that myocyte sarcoplasmic reticulum
      Ca(2+) content may be normal or even increased at slow stimulation rates. This
      may occur because prolonged action potential duration promotes Ca(2+) influx via
      the Na(+)/Ca(2+) exchanger. Despite preserved SR Ca(2+) content, intracellular
      Ca(2+) transients and contractions may be reduced in amplitude because of
      impaired synchronization of Ca(2+) release events throughout the myocyte.

PMID- 12502595
TI  - Na/Ca exchange in heart failure: contractile dysfunction and arrhythmogenesis.
AB  - Congestive heart failure (HF) is characterized by contractile dysfunction and a
      high incidence of sudden death from nonreentrant ventricular arrhythmias, both of
      which involve altered intracellular calcium handling. The focus of this article
      is on the critical role of the Na/Ca exchanger. We demonstrate that upregulation
      of Na/Ca exchanger unloads the sarcoplasmic reticulum (SR), leading to
      contractile dysfunction. At the same time, Na/Ca exchanger underlies the
      arrhythmogenic transient inward current (I(ti)) in HF. Preserved beta-adrenergic
      responsiveness in HF plays a crucial role in increasing SR Ca load, leading to SR
      Ca release and activation of I(ti). In addition, decreased I(K1) (inward
      rectifier) current in HF destabilizes resting membrane potential (E(m)) and
      further enhances arrhythmogenesis mediated by the upregulated Na/Ca exchanger. We
      thus propose a new paradigm in which upregulated Na/Ca exchanger in HF plays a
      dual role in underlying both the contractile dysfunction and arrhythmogenesis in
      the failing heart. Therapeutic approaches to the treatment of HF will need to
      balance increasing SR Ca load with the arrhythmogenic effects of SR Ca overload
      that involve activation of I(ti) carried by Na/Ca exchanger.

PMID- 12502596
TI  - Modulation of contractility in failing human myocytes by reverse-mode Na/Ca
      exchange.
AB  - A decrease in the peak systolic [Ca](i) and slow decay of the Ca(i) transient are
      common features of the end-stage failing human ventricular myocyte and may
      underlie the contractile abnormalities observed in congestive heart failure. The
      role of the Na/Ca exchanger has been a great area of interest given the changes
      observed at the molecular level. Results from these experiments have been
      inconsistent, however, and therefore cellular-based experiments may be required
      to characterize the role of the Na/Ca exchanger in failing human myocardium. We
      review recent data that suggest an increased ability of the Na/Ca exchanger to
      transport Ca into the cytoplasm in failing human myocytes. We hypothesize that
      this increased Ca influx can explain the slowed decay and impaired relaxation of
      failing human ventricular myocytes.

PMID- 12502597
TI  - Decreased beta-adrenergic responsiveness of Na/Ca exchange current in failing pig
      myocytes.

PMID- 12502598
TI  - Ca influx via the Na/Ca exchanger maintains sarcoplasmic reticulum Ca content in
      failing human myocytes.

PMID- 12502599
TI  - Calcium influx via I(NCX) is favored in failing human ventricular myocytes.

PMID- 12502600
TI  - Overexpression of Na+/Ca2+ exchanger attenuates postinfarcted myocardial
      dysfunction.

PMID- 12502601
TI  - Ischemic tolerance of homozygous transgenic mouse hearts overexpressing the
      sodium-calcium exchanger.

PMID- 12502603
TI  - The molecular architecture of calcium microdomains in rat cardiomyocytes.
AB  - We have used standard indirect immunofluorescence techniques in combination with
      wide-field microscopy and image deconvolution to assess the distribution of
      proteins implicated in excitation-contraction coupling and Ca(2+) homeostasis in
      adult rat cardiomyocytes. We begin by discussing our earlier results and
      summarizing what is known about the molecular architecture of this species to
      provide a rationale for the work presented here. The previous results showed that
      the dyads contain Ca(2+) channels and ryanodine receptors, but few Na(+) channels
      or Na(+)/Ca(2+) exchangers. The latter proteins were not colocalized elsewhere on
      the membrane, and we have now found that they appear to be minimally associated
      with caveolin-3. None of the molecules examined are distributed uniformly in the
      membranes in which they are located but are organized into discrete clusters
      attached to the underlying cytoskeleton, an arrangement that, at the level of
      light microscopy, does not appear to be affected by the enzymatic dissociation
      used to study single cells. Analysis of how the clusters are organized and
      distributed throughout the volume of the cell suggests that there may be
      differences in excitation-contraction coupling between the cell surface and the
      interior.

PMID- 12502604
TI  - Na/Ca exchange function in intact ventricular myocytes.
AB  - Here, we address three issues in intact ventricular myocytes that specifically
      relate to the role of Na/Ca exchange (NCX) current under physiological
      conditions. First, we revisit the issue of NCX stoichiometry in light of some
      recent findings that the stoichiometry of the NCX may not be fixed at 3Na: 1Ca.
      We discuss some data that strongly favor the 3:1 stoichiometry, at least under
      physiological conditions. Second, we address the controversy over the role of
      allosteric Ca regulation in intact myocytes. We show that outward and inward
      I(NCX) can be activated dynamically by changing [Ca](i) over the physiological
      range and that outward I(NCX) can be activated quite rapidly with sarcoplasmic
      reticulum Ca release. These data are well described using an instantaneous
      equation for NCX current that includes an allosteric activation factor with
      K(mCaAct) = 125 nM. Finally, we consider the effect on NCX current of submembrane
      elevations in [Ca](i) (that are far greater than are measured in the bulk
      cytoplasm). Taken together with a NCX stoichiometry of 3, these findings have
      allowed us to make some predictions of the role of I(NCX) during an AP. Our
      simulations suggest that NCX current is outward for less than approximately 10 ms
      at the beginning of the action potential.

PMID- 12502605
TI  - Pharmacology of Na+/Ca2+ exchanger.
AB  - KB-R7943 inhibits the Na(+)/Ca(2+) exchanger in an independent manner or in a
      manner dependent on the direction of the current. This effect may be due to the
      experimental protocols bawed on the competition between the drug and external
      substrate ions. Some antiarrhythmic drugs inhibit NCX. A new column of NCX was
      added in Sicilian Gambit.

PMID- 12502606
TI  - Functional consequences of Na/Ca exchanger overexpression in cardiac myocytes.
AB  - Several factors are important in the relationship between Na/Ca exchanger
      overexpression and Ca cycling in physiological and pathophysiological situations.
      First, there are species differences. Transgenic mouse cardiac myocytes
      overexpressing Na/Ca exchanger showed a faster Ca transient associated with
      increased sarcoplasmic reticulum (SR) Ca content compared with wild-type
      myocytes. Cultured rabbit cardiac myocytes overexpressing Na/Ca exchanger showed
      reduced amplitude of the Ca transient and reduced SR Ca content. Second, the
      activity of other Ca regulatory proteins have to be considered. When Ca uptake
      via SR Ca ATPase (SERCA) was reduced by thapsigargin in transgenic mouse myocytes
      overexpressing Na/Ca exchanger, the time course of the Ca transient was slowed,
      and the SR Ca content was reduced to wild-type mouse myocyte levels, suggesting a
      potential compensatory role of Na/Ca exchanger overexpression when SERCA function
      is reduced. Finally, there are confounding factors related to the
      pathophysiological conditions. Our results suggest that Na/Ca exchanger
      overexpression can compensate for defects in SR Ca uptake in mouse myocytes. The
      consequences of Na/Ca exchanger overexpression in other species and conditions is
      unpredictable and require further investigation.

PMID- 12502608
TI  - Volatile anesthetics and regulation of cardiac Na+/Ca2+ exchange in neonates
      versus adults.

PMID- 12502609
TI  - Modulation of the Na+/Ca2+ exchanger by isoprenaline, adenosine, and endothelin-1
      in guinea pig ventricular myocytes.

PMID- 12502610
TI  - Effect of KB-R7943 on oscillatory Na+/Ca2+ exchange current in guinea pig
      ventricular myocytes.

PMID- 12502611
TI  - Inhibition of the Drosophila Na+/Ca2) exchanger, CALX1.1, by KB-R7943.

PMID- 12502614
TI  - Report of the expert committee on the diagnosis and classification of diabetes
      mellitus.

PMID- 12502615
TI  - Screening for type 2 diabetes.

PMID- 12502616
TI  - Implications of the diabetes control and complications trial.

PMID- 12502617
TI  - Implications of the United kingdom prospective diabetes study.

PMID- 12502618
TI  - Standards of medical care for patients with diabetes mellitus.

PMID- 12502619
TI  - Evidence-based nutrition principles and recommendations for the treatment and
      prevention of diabetes and related complications.

PMID- 12502620
TI  - The prevention or delay of type 2 diabetes.

PMID- 12502621
TI  - Translation of the diabetes nutrition recommendations for health care
      institutions.

PMID- 12502622
TI  - Physical activity/exercise and diabetes mellitus.

PMID- 12502623
TI  - Preventive foot care in people with diabetes.

PMID- 12502624
TI  - Treatment of hypertension in adults with diabetes.

PMID- 12502625
TI  - Management of dyslipidemia in adults with diabetes.

PMID- 12502626
TI  - Aspirin therapy in diabetes.

PMID- 12502627
TI  - Smoking and diabetes.

PMID- 12502628
TI  - Preconception care of women with diabetes.

PMID- 12502629
TI  - Diabetic nephropathy.

PMID- 12502630
TI  - Diabetic retinopathy.

PMID- 12502631
TI  - Gestational diabetes mellitus.

PMID- 12502632
TI  - Tests of glycemia in diabetes.

PMID- 12502633
TI  - Hyperglycemic crises in patients with diabetes mellitus.

PMID- 12502634
TI  - Hospital admission guidelines for diabetes mellitus.

PMID- 12502635
TI  - Bedside blood glucose monitoring in hospitals.

PMID- 12502636
TI  - Pancreas transplantation for patients with type 1 diabetes.

PMID- 12502637
TI  - Insulin administration.

PMID- 12502638
TI  - Continuous subcutaneous insulin infusion.

PMID- 12502639
TI  - Immunization and the prevention of influenza and pneumococcal disease in people
      with diabetes.

PMID- 12502640
TI  - Management of diabetes in correctional institutions.

PMID- 12502641
TI  - Care of children with diabetes in the school and day care setting.

PMID- 12502642
TI  - Management of diabetes at diabetes camps.

PMID- 12502643
TI  - Concurrent care.

PMID- 12502644
TI  - Prevention of type 1 diabetes mellitus.

PMID- 12502645
TI  - Hypoglycemia and employment/licensure.

PMID- 12502646
TI  - Unproven therapies.

PMID- 12502647
TI  - Third-party reimbursement for diabetes care, self-management education, and
      supplies.

PMID- 12502650
TI  - National standards for diabetes self-management education.

PMID- 12502651
TI  - Impact of pramlintide on glucose fluctuations and postprandial glucose, glucagon,
      and triglyceride excursions among patients with type 1 diabetes intensively
      treated with insulin pumps.
AB  - OBJECTIVE: To assess the effects of adjunctive treatment with pramlintide, an
      analog of the beta-cell hormone amylin, on 24-h glucose fluctuations and
      postprandial glucose, glucagon, and triglyceride excursions in patients with type
      1 diabetes intensively treated with continuous subcutaneous insulin infusion
      (CSII). RESEARCH DESIGN AND METHODS: In this study, 18 patients (16 of whom could
      be evaluated) with type 1 diabetes (age 44 +/- 11 years, HbA(1c) 8.2 +/- 1.3%
      [mean +/- SD]) were given mealtime injections of 30 micro g pramlintide t.i.d.
      for 4 weeks in addition to their preexisting CSII regimen (16 lispro, 2 regular
      insulin). Mealtime insulin boluses were reduced by a minimum of 10% during the
      first 3 days, and re-adjusted thereafter based on clinical judgment. At weeks 0
      (baseline), 4 (on treatment), and 6 (2 weeks off treatment), 24-h interstitial
      glucose concentrations were measured using a continuous glucose monitoring system
      (CGMS), and postprandial plasma glucose, glucagon, and triglyceride
      concentrations were measured in response to a standardized test meal. RESULTS: At
      baseline, patients had excessive 24-h glucose fluctuations, with 59% of the CGMS
      measurements >140 mg/dl, 13% <80 mg/dl, and only 28% in the euglycemic range (80
      140 mg/dl). After 4 weeks on pramlintide, measurements in the hyperglycemic range
      declined to 48% and measurements within the euglycemic range increased to 37%.
      This shift from the hyperglycemic to the euglycemic range occurred with a
      concomitant 17% reduction in mealtime insulin dosages and without relevant
      increases in measurements below the euglycemic range (15%) or any severe
      hypoglycemic events. After 4 weeks on pramlintide, postprandial glucose,
      glucagon, and triglyceride excursions were reduced by approximately 86,
      approximately 87, and approximately 72%, respectively (incremental areas under
      the curve, all P < 0.05 vs. baseline). At week 6 (off treatment), the 24-h
      glucose profile and postprandial glucose, glucagon, and triglyceride excursions
      approached pretreatment values. CONCLUSIONS: In this study, the addition of
      pramlintide to insulin therapy reduced excessive 24-h glucose fluctuations as
      well as postprandial glucose, glucagon, and triglyceride excursions in patients
      with type 1 diabetes intensively treated with insulin pumps.

PMID- 12502652
TI  - Impact of bedtime snack composition on prevention of nocturnal hypoglycemia in
      adults with type 1 diabetes undergoing intensive insulin management using lispro
      insulin before meals: a randomized, placebo-controlled, crossover trial.
AB  - OBJECTIVE: To determine the impact of four bedtime (HS) snack compositions on
      nocturnal glycemic control, including frequency of hypoglycemia (<4 mmol/l) and
      morning hyperglycemia (>10 mmol/l), in adults with type 1 diabetes using lispro
      insulin before meals and NPH insulin at bedtime. RESEARCH DESIGN AND METHODS:
      Substitutions of 15 g carbohydrate (one starch exchange) for an equivalent amount
      of uncooked cornstarch or pure protein were compared to a standard snack
      (control: two starch + one protein exchange) and to no snack (placebo) in 15
      adults using a randomized, cross-over design. All snacks were equivalent in kcal,
      fat, and total available glucose. An intravenous facilitated hourly blood glucose
      sampling during the night (11:00 P.M. to 7:00 A.M.). RESULTS: The glycemic level
      at bedtime (<7, 7-10, and >10 mmol/l) mediated the effects observed. A total of
      14 hypoglycemic episodes, in 60% of patients, and 23 morning hyperglycemic
      episodes occurred over 50 nights. Most hypoglycemic episodes (10 of 14, 71%)
      occurred with no snack compared to any snack (P < 0.001) and at HS levels of <7
      mmol/l (P = 0.05). The standard and protein snacks resulted in no nocturnal
      hypoglycemia at all HS glucose levels (P < 0.001). Only HS glucose >10 mmol/l was
      protective against hypoglycemia, even in the absence of a snack (P = 0.05); 46%
      of morning hyperglycemic episodes were associated (r = 0.37, P = 0.07) with this
      HS glucose level. CONCLUSIONS: The need for and composition of an HS snack
      depends on the HS glucose such that no snack is necessary at levels >10 mmol/l.
      At levels between 7 and 10 mmol/l, any snack is advised, and at <7 mmol/l, a
      standard or protein snack is recommended.

PMID- 12502653
TI  - Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes:
      the strong heart study.
AB  - OBJECTIVE: To determine whether non-HDL cholesterol, a measure of total
      cholesterol minus HDL cholesterol, is a predictor of CVD in patients with
      diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study, a population-based
      study of CVD and its risk factors in 13 American Indian communities in three
      geographic areas in the U.S. The baseline examination, conducted between July
      1989 and January 1992, consisted of a personal interview, a physical examination,
      and laboratory tests. Of the 4,549 women and men aged 45-74 years participating
      in the study, 2,108 had diabetes but no CVD at baseline. Data on fatal and
      nonfatal CVD were collected during the follow-up period through 31 December 1998
      (average 9 years). RESULTS: Multivariable analyses indicated that non-HDL
      cholesterol is a strong predictor of CVD in men and women with diabetes and is
      particularly indicative of coronary events. Hazard ratios for the highest tertile
      of non-HDL cholesterol in men and women with diabetes (2.23 and 1.80,
      respectively) were higher than those for either LDL cholesterol or triglycerides
      alone in both men and women and were higher than the ratio of total/HDL
      cholesterol in women. The utility of non-HDL cholesterol in predicting CVD
      extended over a wide range of triglyceride concentrations. CONCLUSIONS: This
      study suggests that non-HDL cholesterol index may be particularly useful in
      predicting CVD risk in patients with diabetes.

PMID- 12502654
TI  - Randomized controlled community-based nutrition and exercise intervention
      improves glycemia and cardiovascular risk factors in type 2 diabetic patients in
      rural Costa Rica.
AB  - OBJECTIVE: The prevalence of type 2 diabetes, especially in developing countries,
      has grown over the past decades. We performed a controlled clinical study to
      determine whether a community-based, group-centered public health intervention
      addressing nutrition and exercise can ameliorate glycemic control and associated
      cardiovascular risk factors in type 2 diabetic patients in rural Costa Rica.
      RESEARCH DESIGN AND METHODS: A total of 75 adults with type 2 diabetes, mean age
      59 years, were randomly assigned to the intervention group or the control group.
      All participants received basic diabetes education. The subjects in the
      intervention group participated in 11 weekly nutrition classes (90 min each
      session). Subjects for whom exercise was deemed safe also participated in
      triweekly walking groups (60 min each session). Glycosylated hemoglobin, fasting
      plasma glucose, total cholesterol, triglycerides, HDL and LDL cholesterol,
      height, weight, BMI, and blood pressure were measured at baseline and the end of
      the study (after 12 weeks). RESULTS: The intervention group lost 1.0 +/- 2.2 kg
      compared with a weight gain in the control group of 0.4 +/- 2.3 kg (P = 0.028).
      Fasting plasma glucose decreased 19 +/- 55 mg/dl in the intervention group and
      increased 16 +/- 78 mg/dl in the control group (P = 0.048). Glycosylated
      hemoglobin decreased 1.8 +/- 2.3% in the intervention group and 0.4 +/- 2.3% in
      the control group (P = 0.028). CONCLUSIONS: Glycemic control of type 2 diabetic
      patients can be improved through community-based, group-centered public health
      interventions addressing nutrition and exercise. This pilot study provides an
      economically feasible model for programs that aim to improve the health status of
      people with type 2 diabetes.

PMID- 12502655
TI  - Effect of leptin replacement on intrahepatic and intramyocellular lipid content
      in patients with generalized lipodystrophy.
AB  - OBJECTIVE: To investigate whether leptin-induced improvements in glycemic
      control, hyperlipidemia, and insulin sensitivity in hypoleptinemic patients with
      generalized lipodystrophies are accompanied by reduction in intrahepatic and
      intramyocellular lipid (IMCL) accumulation. RESEARCH DESIGN AND METHODS: We
      examined the effects 8-10 months of subcutaneous leptin replacement therapy on
      insulin sensitivity, IMCL, and intrahepatic lipid content in two patients with
      acquired generalized lipodystrophy and one patient with congenital generalized
      lipodystrophy. All patients had extreme lack of body fat, low plasma leptin
      levels, and elevated serum triglycerides, but only two had diabetes. Insulin
      sensitivity was measured by a high-dose (0.2 IU/kg) insulin tolerance test, as
      well as by hyperinsulinemic-euglycemic glucose clamp studies in two patients.
      IMCL and intrahepatic lipid content were measured by (1)H magnetic resonance
      spectroscopy. All measurements were obtained before and during 2-10 months of
      leptin therapy. RESULTS: Glycemic control and lipoprotein levels markedly
      improved with leptin therapy in the two diabetic patients, and a slight
      improvement in lipoprotein levels was seen in the nondiabetic patients. Insulin
      stimulated glucose uptake during 60-120 min of the euglycemic clamp studies, and
      the rate of glucose disappearance during the insulin tolerance test nearly
      doubled with leptin therapy. As compared with the baseline period, after 8-10
      months of leptin therapy, the mean intrahepatic lipid content was reduced by
      approximately 80% and the IMCL content was reduced by approximately 42%.
      CONCLUSIONS: Reduction in IMCL and intrahepatic lipid content may partly explain
      leptin-induced improvement in insulin sensitivity in patients with generalized
      lipodystrophy.

PMID- 12502656
TI  - Costs associated with the primary prevention of type 2 diabetes mellitus in the
      diabetes prevention program.
AB  - OBJECTIVE: To describe the costs of the Diabetes Prevention Program (DPP)
      interventions to prevent or delay type 2 diabetes. RESEARCH DESIGN AND METHODS:
      We describe the direct medical costs, direct nonmedical costs, and indirect costs
      of the placebo, metformin, and intensive lifestyle interventions over the 3-year
      study period of the DPP. Resource use and cost are summarized from the
      perspective of a large health system and society. Research costs are excluded.
      RESULTS: The direct medical cost of laboratory tests to identify one subject with
      impaired glucose tolerance (IGT) was $139. Over 3 years, the direct medical costs
      of the interventions were $79 per participant in the placebo group, $2,542 in the
      metformin group, and $2,780 in the lifestyle group. The direct medical costs of
      care outside the DPP were $272 less per participant in the metformin group and
      $432 less in the lifestyle group compared with the placebo group. Direct
      nonmedical costs were $9 less per participant in the metformin group and $1,445
      greater in the lifestyle group compared with the placebo group. Indirect costs
      were $230 greater per participant in the metformin group and $174 less in the
      lifestyle group compared with the placebo group. From the perspective of a health
      system, the cost of the metformin intervention relative to the placebo
      intervention was $2,191 per participant and the cost of the lifestyle
      intervention was $2,269 per participant over 3 years. From the perspective of
      society, the cost of the metformin intervention relative to the placebo
      intervention was $2,412 per participant and the cost of the lifestyle
      intervention was $3,540 per participant over 3 years. CONCLUSIONS: The metformin
      and lifestyle interventions are associated with modest incremental costs compared
      with the placebo intervention. The evaluation of costs relative to health
      benefits will determine the value of these interventions to health systems and
      society.

PMID- 12502657
TI  - Alcohol consumption and risk for development of impaired fasting glucose or type
      2 diabetes in middle-aged Japanese men.
AB  - OBJECTIVE: To investigate the association between alcohol consumption and risk
      for development of diabetes. RESEARCH DESIGN AND METHODS: We examined 2,953
      Japanese male office workers aged 35-59 years who did not have impaired fasting
      glucose (IFG) (a fasting plasma glucose concentration of 6.1-6.9 mmol/l), type 2
      diabetes (a fasting plasma glucose concentration of > or =7.0 mmol/l or receipt
      of hypoglycemic medication), medication for hypertension, or a history of
      cardiovascular disease. Fasting plasma glucose concentrations were measured at
      periodic annual health examinations from May 1994 through May 2001. RESULTS:
      There was a U-shaped association between alcohol consumption and the incidence of
      IFG or type 2 diabetes during 7 years of follow-up, with the lowest incidence at
      alcohol intake of 23.0-45.9 g ethanol/day. After controlling for age, family
      history of diabetes, BMI, cigarette smoking, and physical activity, the relative
      risk for development of IFG or type 2 diabetes compared with alcohol consumption
      of 23.0-45.9 g ethanol/day was 1.51 (95% CI, 1.07-2.13), 1.31 (95% CI, 0.93
      1.84), 1.18 (95% CI, 0.87-1.61), and 1.43 (95% CI, 1.01-2.02) with alcohol
      consumption of 0, 0.1-22.9, 46.0-68.9, and > or =69.0 g ethanol/day, respectively
      (P for quadratic trend = 0.016). Analyses by presence or absence of a risk factor
      revealed that a U-shaped association was more evident in older men, men without a
      family history of diabetes, and nonsmokers. CONCLUSIONS: These results indicate
      that moderate alcohol consumption among apparently healthy Japanese men is
      associated with reduced risk for development of IFG or type 2 diabetes.

PMID- 12502658
TI  - Prevalence of diabetes is higher among female than male Zuni indians.
AB  - OBJECTIVE: Test the hypothesis that diabetes and related risk factors are more
      common among female than male Zuni Indians. RESEARCH DESIGN AND METHODS: We
      conducted a population-based, cross-sectional survey of the Zuni Indians aged >
      or =5 years. We used households within neighborhood clusters as the sampling
      frame. We administered a questionnaire, collected blood and urine, and measured
      height and weight. Self-reported diabetes was used to assess previously diagnosed
      diabetes. Participants without a prior history of diabetes were classified as
      having newly diagnosed diabetes if they had HbA(1c) >7.0% or random glucose > or
      =11.1 mmol/l during the survey. RESULTS: The prevalence of previously diagnosed
      diabetes among Zuni Indians aged > or =5 years (n = 1,503) was higher among
      female Zuni Indians (16.7% [95% CI 14.1-19.3]) than male Zuni Indians (9.7% [7.4
      12.1]) (P < 0.001). The prevalence of newly diagnosed diabetes was similar among
      female Zuni Indians (2.4% [1.4-3.4]) and male Zuni Indians (2.4% [1.2-3.6]). The
      prevalence of previously and newly diagnosed diabetes was higher among female
      Zuni Indians (19.1% [16.4-21.9]) than male Zuni Indians (12.2% [9.5-14.8]) (P <
      0.001). The prevalence of obesity was higher among female Zuni Indians (34.3%
      [30.9-37.7]) than male Zuni Indians (21.5% [18.4-24.7]) (P < 0.001). Obesity was
      associated with diabetes among female and male Zuni Indians. Physical inactivity
      was more common among female Zuni Indians (44.2% [40.7-47.8]) than male Zuni
      Indians (35.1% [31.5-38.7]) (P < 0.001). However, physical inactivity was not
      associated with diabetes among either female or male Zuni Indians. Gestational
      diabetes was a risk factor among female Zuni Indians. CONCLUSIONS: Among the Zuni
      Indians, the prevalence of diabetes was 57% higher among female than male members
      of the population. Culture, tradition, and lifestyle differences may contribute
      to the higher prevalence of diabetes and obesity among female Zuni Indians.

PMID- 12502659
TI  - Age- and sex-specific prevalences of diabetes and impaired glucose regulation in
      13 European cohorts.
AB  - OBJECTIVE: To report the age- and sex-specific prevalences of diabetes and
      impaired glucose regulation (IGR) according to the revised 1999 World Health
      Organization criteria for diabetes in Europe. RESEARCH DESIGN AND METHODS: A
      total of 13 studies from nine European countries with 7,680 men and 9,251 women
      aged 30-89 years were included in the data analysis. RESULTS: In most of the
      study populations, the age-specific prevalences of diabetes were <10% in subjects
      younger than 60 years and between 10 and 20% at 60-79 years of age. Mean 2-h
      plasma glucose (2hPG) concentration increased linearly with age, but fasting
      plasma glucose (FPG) concentration did not. The increase in the prevalence of
      undiagnosed diabetes and IGR in the elderly was mainly a result of the large
      increase in 2hPG rather than FPG. Diabetes and impaired fasting glycemia defined
      by isolated fasting hyperglycemia was more common in men than in women 30-69
      years of age, whereas the prevalence of isolated postload hyperglycemia,
      particularly impaired glucose tolerance, was higher in women than in men,
      especially in the elderly (individuals >70 years of age). More than half of the
      diabetes was undiagnosed in subjects younger than 50 years of age. CONCLUSIONS:
      Most European populations have a moderate to low prevalence of diabetes and IGR.
      Diabetes and IGR will be underestimated in Europe, particularly in women and in
      elderly men, if diagnoses are based on fasting glucose determination alone.

PMID- 12502660
TI  - Progression of lower-extremity disability in older women with diabetes: the
      Women's Health and Aging Study.
AB  - OBJECTIVE: Older patients with diabetes are more likely to have a higher
      prevalence of multiple risk factors for physical disability, as a result of
      diabetic complications. We evaluated the pace of decline in lower-extremity
      function and the risk for progression of disability in older women with diabetes.
      RESEARCH DESIGN AND METHODS: We conducted a 3-year longitudinal cohort study of a
      random sample of 729 physically impaired older women (age > or =65 years) living
      in the community (Baltimore, MD). Diabetes was ascertained by standard criteria.
      Self-reported functional status and objective performance measures were assessed
      at baseline and over six semiannual follow-up visits. RESULTS: The baseline
      prevalence of diabetes was 14.4%. After adjustment for age and compared with
      women without diabetes, those with diabetes had an RR of 1.8 (95% CI 1.3-2.5) for
      incident mobility disability and 1.6 (1.2-2.1) for incident activity of daily
      living disability. The increased incidence of new disability associated with
      diabetes was paralleled by a greater decline in objective measures of lower
      extremity function. Adjustment for multiple risk factors for disability did not
      significantly attenuate the risk for disability associated with diabetes.
      CONCLUSIONS: In older patients, impaired lower-extremity function is a long-term
      diabetic complication. Comprehensive assessment of older diabetic patients should
      include a standardized evaluation of lower-extremity performance.

PMID- 12502661
TI  - Incidence of retinopathy and nephropathy in youth-onset compared with adult-onset
      type 2 diabetes.
AB  - OBJECTIVE: To examine the risk of retinopathy and nephropathy in participants in
      whom type 2 diabetes was diagnosed in youth (before 20 years of age) compared
      with those in whom type 2 diabetes was diagnosed at older ages. RESEARCH DESIGN
      AND METHODS: Subjects in whom youth-onset or adult-onset diabetes was diagnosed
      in the longitudinal study of health in the Pima Indians of Arizona were followed
      for microvascular complications. Diabetes was diagnosed in 178 subjects before 20
      years of age (youth), in 1,359 subjects at 20-39 years of age (younger adults),
      and in 971 subjects at 40-59 years of age (older adults). Incidence rates of
      diabetic retinopathy diagnosed by direct ophthalmoscopy through dilated pupils
      and nephropathy (protein-to-creatinine ratio > or =0.5 g/g) were calculated by
      age at diagnosis. RESULTS: Over 25 years, nephropathy developed in 35 of the
      participants with youth-onset type 2 diabetes; this incidence rate was not
      significantly different from that in patients with adult-onset diabetes (P =
      0.77). Incidence rates of retinopathy, however, were significantly lower for the
      youth-onset group (P = 0.007). Adjusted for sex, glycemia, and blood pressure,
      risk of retinopathy was lower in patients with youth-onset diabetes than in those
      with adult-onset diabetes (hazard rate ratio [HRR] 0.42, 95% CI 0.24-0.74, P =
      0.003), but risk of nephropathy was not different (HRR 1.2, 95% CI 0.77-1.3, P =
      0.38). CONCLUSIONS: In Pima Indians, the risk of nephropathy as a function of
      duration of diabetes is similar in all age groups. By contrast, the risk of
      retinopathy is lower in patients with youth-onset type 2 diabetes.

PMID- 12502662
TI  - Autoimmune gastropathy in type 1 diabetic patients with parietal cell antibodies:
      histological and clinical findings.
AB  - OBJECTIVE: Approximately 15-20% of type 1 diabetic patients exhibit parietal cell
      antibodies (PCAs) targeting gastric H+/K+ATPase. We examined whether iron
      deficiency anemia, pernicious anemia, and autoimmune gastritis, which may
      predispose to gastric tumors, were more frequent in PCA+ than in PCA- patients.
      RESEARCH DESIGN AND METHODS: Gastric biopsies from 88 consecutively recruited
      type 1 diabetic patients (51 men and 37 women, 47 PCA+ and 41 PCA-, aged 42 +/-
      13 years) were evaluated using the updated Sydney system. Immunostaining was done
      for parietal cells, B- and T-cells, enterochromaffin-like (ECL) cells, and
      Helicobacter pylori (HP). PCAs were assayed by indirect immunofluorescence,
      H+/K+ATPase antibodies by enzyme immunoassay, and HP by serology, urea breath
      test, and histology. Pentagastrin tests were performed in 42 subjects. RESULTS:
      Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR
      12.5, P < 0.0001). PCA positivity (beta = 1.44; P = 0.04) and hypergastrinemia
      (beta = 0.01; P = 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ
      type were risk factors for AG. Iron deficiency anemia (OR 3.9, P = 0.015),
      pernicious anemia (OR = 4.6, P = 0.022), and hypochlorhydria (OR = 20.0, P =
      0.0002) were more frequent in AG+ individuals. HP infection was present in 47
      patients but did not influence corpus histology or gastrinemia. (Pre)malignant
      lesions were found in 26% of PCA+ subjects: ECL cell hyperplasia in 7 AG+
      patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal
      metaplasia in 11 AG+ patients, including 1 with linitis plastica. CONCLUSIONS:
      PCA+ type 1 diabetic patients should be screened for autoimmune gastritis, iron
      deficiency, and pernicious anemia. Particularly hypergastrinemic PCA+ patients
      with autoimmune gastritis are at increased risk for (pre)malignant gastric
      lesions.

PMID- 12502663
TI  - Effect of long-term exposure to insulin lispro on the induction of antibody
      response in patients with type 1 or type 2 diabetes.
AB  - OBJECTIVE: To determine the long-term effects of insulin lispro on inducing
      lispro-specific, insulin-specific, and cross-reactive (reactive with both insulin
      lispro and human insulin) antibodies. RESEARCH DESIGN AND METHODS: A
      multinational, multicenter combination of controlled and noncontrolled, open
      label studies of 4.5 years' duration was designed to evaluate the long-term
      immunologic profile of subcutaneously administered insulin lispro. A total of
      1,221 patients (men and women; 12-81 years of age) with type 1 or type 2 diabetes
      were enrolled. Circulating anti-insulin antibodies were measured using
      radioimmunoassays. RESULTS: Insulin-specific and lispro-specific antibody
      responses were within the background noise levels of the assays. Significant
      elevations of antibody were confined to a cross-reactive antibody response.
      Antibody levels resulting from prior exposure to long- and short-acting insulins
      changed little after transfer to insulin lispro and remained within or near the
      baseline levels. De novo exposure to insulin lispro resulted in increases in
      cross-reactive but not insulin- or lispro-specific antibody levels. Cross
      reactive insulin antibodies developed more readily in patients with type 1
      diabetes than in those with type 2 diabetes. Long-term antibody responses tended
      to decrease over time and returned to baseline or near-baseline levels by the end
      of the long-term studies. No evidence of an anamnestic antibody response could be
      found in individuals treated intermittently with insulin lispro. CONCLUSIONS: The
      immunogenic profile of patients treated with insulin lispro was comparable to
      that of patients treated with recombinant human insulin. Inductions of
      significant levels of specific or cross-reactive antibodies were not observed in
      patients who had received insulin previously. No significant antibody-dependent
      increases in insulin dosage requirements were noted in these patients. The
      incidence of insulin allergy was not different from that in patients treated with
      recombinant regular human insulin.

PMID- 12502664
TI  - Life course influences on insulin resistance: findings from the British Women's
      Heart and Health Study.
AB  - OBJECTIVE: To assess the independent associations of a broad range of early life
      risk factors and adult obesity with adult insulin resistance. RESEARCH DESIGN AND
      METHODS: This was a cross-sectional study of 1,394 women, aged 60-79 years, from
      23 British towns. RESULTS: There was a strong (independent of confounding
      factors, other early life factors, and adult waist-to-hip ratio) inverse
      association between birth weight and insulin resistance in women in the highest
      third of BMI (>28.77 kg/m2): -0.12 (95% CI -0.19 to -0.04) log homeostasis model
      assessment (HOMA) score per 1 SD birth weight, but no association between birth
      weight and insulin resistance in women in the two lowest thirds of BMI (P for
      interaction = 0.04). Offspring birth weight, own leg length, and childhood manual
      social class did not interact with adult obesity and were all independently
      inversely associated with insulin resistance: -0.05 (-0.09 to -0.01) log HOMA
      score per 1 SD offspring birth weight, -0.09 (-0.12 to -0.06) log HOMA score per
      1 SD leg length, and a -0.07 (-0.14 to 0.00) difference in log HOMA score between
      manual and nonmanual childhood social class. Childhood manual social class and
      shorter leg length were both independently associated with adverse lipid
      profiles. BMI and waist-to-hip ratio were independently positively associated
      with insulin resistance and with all other components of the insulin resistance
      syndrome. CONCLUSIONS: Insulin resistance is an important risk factor for type 2
      diabetes and coronary heart disease. Our results suggest that genetic factors,
      intrauterine environment, early childhood, and adult environmental factors are
      all relevant in determining adult insulin resistance.

PMID- 12502665
TI  - Independent factors associated with major depressive disorder in a national
      sample of individuals with diabetes.
AB  - OBJECTIVE: To determine whether perceived poor physical health, duration of
      diabetes, and smoking are associated with major depressive disorder in a national
      sample of individuals with diabetes. RESEARCH DESIGN AND METHODS: Data on 1,810
      individuals with diabetes from the 1999 National Health Interview Survey (NHIS)
      were analyzed. The Composite International Diagnostic Interview (CIDI) Short-Form
      (CIDI-SF) developed by the World Health Organization was used to identify
      individuals with major depressive disorder. Multiple logistic regression was used
      to determine whether perceived poor physical health, duration of diabetes, and
      smoking were associated with major depressive disorder. The model controlled for
      age, sex, race/ethnicity, education, income, employment, marital status, and
      health status. Other control variables included BMI, smoking, duration of
      diabetes, presence or absence of major complications, and type of treatment for
      diabetes. SUDAAN software was used for statistical analyses to account for the
      complex sampling design of NHIS. RESULTS: Independent factors associated with
      major depressive disorder were age <64 years, female sex, at least high school
      education, income <124% of federal poverty level, perceived worsening of health
      status, and smoking. CONCLUSIONS: In addition to other psychosocial factors such
      as younger age, female sex, lower income, at least high school education, and
      smoking, perceptions about the effect of diabetes on overall health seems to play
      an important role in the etiology of depression.

PMID- 12502666
TI  - Factors associated with academic achievement in children with type 1 diabetes.
AB  - OBJECTIVE: To examine academic achievement in children with diabetes and to
      identify predictors of achievement. RESEARCH DESIGN AND METHODS: Participants
      were 244 children, ages 8-18 years, with type 1 diabetes. Measures included
      school-administered standardized achievement tests (Iowa Tests of Basic Skills
      and Iowa Tests of Educational Development [ITBS/ITED]), grade point averages
      (GPAs), school absences, behavioral assessment, age at disease onset,
      hospitalizations, and HbA(1c). Statistical differences between subgroups of
      children were evaluated using t test and ANOVA, statistically controlling for
      socioeconomic status. Regression analyses were carried out to examine predictors
      of academic performance. RESULTS: Reading scores and GPA were lower for children
      with poor metabolic control than for children with average control. Children with
      hospitalizations for hyperglycemia had lower overall achievement scores than
      children with better metabolic control and fewer hospitalizations for
      hyperglycemia. The small group of children with tight metabolic control and
      hypoglycemic hospitalizations scored particularly low on the ITBS/ITED. Other
      variables had less clear relationships with academic achievement. Neither early
      onset of diabetes nor frequent school absence was associated with lower scores on
      the ITBS/ITED. Sex comparisons found that boys performed better than girls only
      in math. Socioeconomic status and parent ratings of behavior problems were
      significantly correlated with academic achievement, but medical variables added
      only slightly to predictive precision. CONCLUSIONS: For most children with
      diabetes, medical variables are not as strongly associated with academic
      achievement as are factors such as socioeconomic status and behavioral factors.
      Poor metabolic control and serious hypoglycemia, however, are a potential concern
      for a subset of these children.

PMID- 12502667
TI  - Prevalence and concomitants of glucose intolerance in European obese children and
      adolescents.
AB  - OBJECTIVE: The worldwide increase in the prevalence of childhood obesity is
      reaching epidemic proportions and is associated with a dramatic rise in cases of
      type 2 diabetes. The prevalence of glucose intolerance and its determinants and
      the relation of cardiovascular risk factors with levels of glycemia and degree of
      obesity were studied in grossly obese children of European origin. RESEARCH
      DESIGN AND METHODS: A total of 710 grossly obese Italian children (SD score [SDS]
      of BMI 3.8 +/- 0.7) aged 6-18 years, including 345 male subjects, underwent an
      oral glucose tolerance test. Insulin resistance and insulin secretion were
      estimated using the homeostasis model assessment for insulin resistance and the
      insulinogenic index, respectively. Fibrinogen, C-reactive protein, lipids, and
      uric acid were measured. The 2-h postload glucose and degree of obesity,
      calculated as the SDS of weight/height(2), were used as dependent variables.
      RESULTS: The prevalence of glucose intolerance was 4.5%. Insulin resistance (P <
      0.0001), impaired insulin secretion (P < 0.0001), and diastolic blood pressure
      (BP) (P < 0.05) were significantly and independently related to 2-h postload
      glucose values. The degree of obesity did not relate to insulin resistance but
      was independently correlated with inflammatory proteins, uric acid, and systolic
      BP, variables that were often abnormal in this population. CONCLUSIONS: In these
      grossly obese children, both insulin resistance and impaired insulin secretion
      contribute to the elevation of glycemia, and the degree of obesity is related to
      cardiovascular risk factors independently of insulin resistance.

PMID- 12502668
TI  - A randomized trial of sibutramine in the management of obese type 2 diabetic
      patients treated with metformin.
AB  - OBJECTIVE: To evaluate the effects of sibutramine (15 and 20 mg/day) on weight,
      metabolic control, and blood pressure in metformin-treated obese subjects with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: A 12-month randomized prospective
      placebo-controlled double-blind study was performed. It included 21 primary and
      secondary care centers in England, Canada, France, and Belgium. A total of 195
      subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied.
      Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c),
      fasting glucose, and lipids. RESULTS: Sibutramine induced significant weight loss
      (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0
      +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was
      achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by
      none given placebo. Glycemic control improved in parallel with weight loss, and
      subjects who lost > or = 10% weight showed significant decreases in both HbA(1c)
      (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001).
      HDL cholesterol increased slightly with the higher dose, whereas plasma
      triglycerides fell with both doses, especially in subjects with weight loss of >
      or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated.
      Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in
      a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with
      placebo, P < 0.05), but this effect was less evident in subjects who had a weight
      loss of > or = 10% weight. Pulse rate increased significantly more with
      sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17%
      with placebo (P < 0.01). CONCLUSIONS: Sibutramine can be an effective adjunct to
      metformin treatment in selected obese type 2 diabetic subjects and improves
      metabolic control in individuals who lose weight.

PMID- 12502669
TI  - Intrarenal hemodynamic changes after captopril test in patients with type 2
      diabetes: a duplex Doppler sonography study.
AB  - OBJECTIVE: ACE inhibitors are known to be effective in preventing the progression
      of diabetic nephropathy. Activation of the renin-angiotensin system (RAS) is
      reported to contribute to intrarenal hemodynamic abnormality in diabetic
      patients. We examined whether RAS blockade by captopril induces intrarenal
      hemodynamic changes in normotensive patients with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: The patients ranged in age from 40 to 65 years (20 men and 20
      women). A total of 15 age- and sex-matched healthy individuals served as control
      subjects. Resistive index (RI) of interlobar arteries was examined by duplex
      Doppler sonography before and after the oral captopril (25 mg) test. RESULTS: At
      baseline, no significant differences in RI values or plasma renin activity (PRA)
      were seen between the patients and healthy subjects. In healthy subjects, the RI
      values after the captopril test were significantly higher than baseline values (P
      < 0.01). However, in patients with type 2 diabetes, both with normoalbuminuria
      and microalbuminuria, RI values after the test were significantly lower than
      baseline values (P < 0.001). There were significant negative correlations between
      DeltaRI value and HbA1c (r = -0.458, P < 0.005) and between DeltaRI value and
      baseline PRA in diabetic patients (r = -0.339, P < 0.05). Multiple regression
      analysis showed that HbA1c and baseline PRA significantly and independently
      affected the magnitude of decrease in RI values after captopril administration in
      diabetic patients (R2 = 0.391, P < 0.0001). CONCLUSIONS: These results indicate
      that the intrarenal RAS may be activated in diabetic patients, that such
      activation may be affected by poor glycemic control, and that blockade of RAS
      activation by ACE inhibitor reduces intrarenal vascular resistance in diabetic
      patients. The results emphasize the beneficial effects of ACE inhibition in
      improving intrarenal hemodynamics in diabetic patients.

PMID- 12502670
TI  - Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin
      resistance: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether, in adolescents with type 1 diabetes, the addition
      of metformin to insulin and standard diabetes management results in 1) higher
      insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units
      per kilogram per day) and BMI. RESEARCH DESIGN AND METHODS: This was a
      randomized, placebo-controlled 3-month trial of metformin therapy in 27
      adolescents with type 1 diabetes, high insulin dosage (>1 unit. kg(-1). day(-1)),
      and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled
      intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at
      the onset and end of treatment. RESULTS: At t = 0, HbA1c was 9.2 +/- 0.9%,
      insulin dosage was 1.2 +/- 0.2 units. kg(-1). day(-1), fasting glucose was 10.6
      +/- 2.4 mmol/l, and BMI was 24.2 +/- 3.9 kg/m2 (means +/- SD), with no difference
      between the metformin and placebo groups. At the end of the study, HbA1c was 0.6%
      lower in the metformin group than in the placebo group (P < 0.05). This was
      achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs.
      placebo group 0.02 +/- 0.2 units. kg(-1). day(-1); P < 0.05), with no significant
      change in BMI. Fasting glucose levels improved significantly in the metformin
      group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not
      significantly different between the two groups at study end. Mild hypoglycemia
      occurred more frequently in the metformin-treated than in the placebo subjects
      (1.75 +/- 0.8 vs. 0.9 +/- 0.4 events. patient(-1). week(-1); P = 0.03). There
      were no differences in frequency of severe hypoglycemic episodes or
      gastrointestinal complaints between the two groups. CONCLUSIONS: Metformin
      treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens
      with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity
      were not documented in this study using the FSIGT. Long-term studies will
      determine whether these improvements are sustained and whether certain subgroups
      accrue greater benefit from this therapy.

PMID- 12502671
TI  - The relationship between dysglycemia and atherosclerosis in South Asian, Chinese,
      and European individuals in Canada: a randomly sampled cross-sectional study.
AB  - OBJECTIVE: Raised glucose levels extending from normal into the diabetic range
      (dysglycemia) are an emerging risk factor for clinical cardiovascular events. The
      relationship between dysglycemia and atherosclerosis (AS) in the general
      population and in different ethnic groups remains controversial. RESEARCH DESIGN
      AND METHODS: Glucose tolerance, HbA1c, other metabolic risk factors for AS, and
      carotid mean maximal intimal media thickness were assessed in a random sample of
      979 Canadians of South Asian, Chinese, and European descent. RESULTS: The age and
      sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase
      in HbA1c in all participants (P < 0.0001) and in those of South Asian (P =
      0.018), Chinese (P = 0.002), and European (P < 0.0001) descent. This progressive
      curvilinear relationship was most apparent at HbA1c levels >5.7%. The HbA1c-AS
      relationship persisted after adjustment for ethnicity, age, sex, diabetes status,
      abdominal obesity, insulin resistance, insulin secretion, fasting free fatty
      acids, blood pressure, and/or dyslipidemia (P < 0.004). Both diabetes (P = 0.002)
      and HbA1c (P < 0.0001) were determinants of the intimal medial thickness when
      included in separate statistical models. When included together in a single
      model, HbA1c (P < 0.0001) but not diabetes (P = 0.6) was a significant
      determinant. CONCLUSIONS: The degree of AS is related to the level of HbA1c
      irrespective of diabetes status and independent of abdominal obesity and other
      markers of the metabolic syndrome. This progressive relationship between HbA1c
      and AS was observed within different ethnic groups.

PMID- 12502672
TI  - Optimal dose of candesartan for renoprotection in type 2 diabetic patients with
      nephropathy: a double-blind randomized cross-over study.
AB  - OBJECTIVE: We evaluated the optimal dose of the angiotensin II receptor
      antagonist candesartan cilexetil for renoprotection as reflected by short-term
      changes in albuminuria in hypertensive type 2 diabetic patients with nephropathy.
      RESEARCH DESIGN AND METHODS: A total of 23 hypertensive patients with type 2
      diabetes and nephropathy were enrolled in this double-blind randomized cross-over
      trial with four treatment periods, each lasting 2 months. Each patient received
      placebo and candesartan: 8, 16, and 32 mg daily in random order. Antihypertensive
      medication was discontinued before enrollment, except for long-acting furosemide,
      which all patients received throughout the study in median (range) doses of 40
      (30-160) mg daily. End points were albuminuria (turbidimetry), 24-h blood
      pressure (BP) (Takeda-TM2420), and glomerular filtration rate (GFR) (51Cr-labeled
      EDTA plasma clearance technique). RESULTS: Values obtained during placebo
      treatment: albuminuria [geometric mean (95% CI)] 700 (486-1,007) mg/24-h, 24-h BP
      (mean +/- SE) 147 +/- 4/78 +/- 2 mmHg, and GFR 84 +/- 6 ml/min/1.73 m2. All three
      doses of candesartan significantly reduced albuminuria and 24-h BP compared with
      placebo. Mean (95% CI) reductions in albuminuria were 33% (21-43), 59% (52-65),
      and 52% (44-59) with increasing doses of candesartan. Albuminuria was reduced
      significantly more by the two highest doses than by the lowest dose (P < 0.01);
      24-h systolic BP was reduced by 9 (2-16), 9 (2-16), and 13 (6-20) mmHg and 24-h
      diastolic BP was reduced by 5 (2-8), 4 (1-7), and 6 (3-9) mmHg with increasing
      doses of candesartan. There were no significant differences in the reductions in
      BP between the three doses. GFR was decreased by approximately 6 ml/min/1.73 m2
      by all three doses of candesartan (P < 0.05 versus placebo). CONCLUSIONS: The
      optimal dose of candesartan is 16 mg daily for renoprotection, as reflected by
      short-term reduction in albuminuria, in hypertensive type 2 diabetic patients
      with nephropathy.

PMID- 12502673
TI  - Autoregulation of glomerular filtration rate in patients with type 2 diabetes
      during isradipine therapy.
AB  - OBJECTIVE: Calcium-channel blockade impairs renal autoregulation in animals.
      Impaired renal autoregulation leads to transmission of the systemic blood
      pressure (BP) into the glomerulus, resulting in capillary hypertension.
      Information on the impact of calcium antagonist treatment on renal autoregulation
      in humans is lacking. This study examines the effect of isradipine treatment on
      the autoregulation of the glomerular filtration rate (GFR). RESEARCH DESIGN AND
      METHODS: We performed a randomized double-blind crossover study with 5 mg o.d.
      isradipine retard and matching placebo in 16 hypertensive patients with type 2
      diabetes. Each treatment arm lasted 4 weeks. On the last day of each treatment
      period, GFR (single-shot 51Cr-EDTA plasma clearance technique for 4 h) was
      measured twice between 8:00 A.M. and 5:00 P.M., first without clonidine and then
      after intravenous injection of 75 micro g clonidine. BP was measured every 10 min
      (Takeda TM2420; A&D, Tokyo). RESULTS: Clonidine reduced mean arterial BP (MABP)
      by 15 +/- 1 vs. 11 +/- 1 mmHg (means +/- SE) during placebo and isradipine
      treatment, respectively (P < 0.05). GFR was reduced from 102 +/- 4 to 99 +/- 4
      ml. min(-1). 1.73 m(-2) with placebo (P < 0.01) and from 106 +/- 5 to 98 +/- 5
      ml. min(-1). 1.73 m(-2) during treatment with isradipine (P < 0.01). Mean
      difference (95% CI) between changes in GFR with placebo and isradipine was -4.6
      ml. min(-1). 1.73 m(-2) (-10.0 to 0.6) (P = 0.08). Six patients had a reduction
      in GFR >13% (exceeding the normal limit of autoregulation) combined with a
      complete pressure-passive vasculature (defined as DeltaMABP% < or = DeltaGFR%)
      during isradipine treatment versus none during the placebo treatment (P < 0.05).
      CONCLUSIONS: Isradipine impairs GFR autoregulation in a sizeable proportion of
      hypertensive type 2 diabetic patients.

PMID- 12502674
TI  - Discordance between HbA1c and fructosamine: evidence for a glycosylation gap and
      its relation to diabetic nephropathy.
AB  - OBJECTIVE: Discordances between HbA1c and other measures of glycemic control are
      common in clinical practice and remain unexplained. We developed a measure of
      discordance between HbA1c and fructosamine (FA) (glycosylated serum proteins) to
      conduct a systematic evaluation. We termed this the glycosylation gap (GG) and
      sought to determine its relationship to diabetic nephropathy. RESEARCH DESIGN AND
      METHODS: Measurements of HbA1c and FA on the same sample in 153 people were used
      to calculate GG, defined as the difference between measured HbA1c and HbA1c
      predicted from FA based on the population regression of HbA1c on FA. RESULTS: GG
      had a broad distribution (range, -3.2% to 5.5%); 40% of samples had values
      indicating major differences in prediction of complications risk by the measured
      versus predicted HbA1c. GG was highly correlated (r = 0.81) between measurements
      repeated in 65 patients 23 +/- 2 weeks apart, indicating that the discordances
      are reliable and not explained by differences in turnover of underlying proteins.
      In 40 patients with type 1 diabetes of >or = 15 years' duration, an increase in
      GG by 1% was associated with a 2.9-fold greater frequency of increasing
      nephropathy stage (P = 0.0014). GG was -0.8 +/- 0.2% in subjects with no
      nephropathy, -0.3 +/- 0.2% with microalbuminuria/hypertension, and 0.7 +/- 0.3%
      in subjects with proteinuria or renal dysfunction (P < 0.05). GG correlated
      better with nephropathy than did either HbA1c or FA alone in this population.
      CONCLUSIONS: The glycosylation gap may be a useful clinical research tool for
      evaluating physiologic sources of variation in diabetic complications beyond
      glycemic control.

PMID- 12502675
TI  - L-arginine: an ultradian-regulated substrate coupled with insulin oscillations in
      healthy volunteers.
AB  - OBJECTIVE: Coupled oscillations of 50-110 min in insulin and glucose have been
      found previously in healthy men under continuous enteral nutrition. Because L
      arginine induces insulin release as glucose does, we tested the hypothesis that L
      arginine can also display such an ultradian rhythm. RESEARCH DESIGN AND METHODS:
      Seven healthy male subjects participated in one experimental night during which
      blood was sampled every 10 min from 2300 to 0700. Plasma glucose, C-peptide, and
      L-arginine levels were measured simultaneously. The insulin secretion rate (ISR)
      was calculated from plasma C-peptide levels by a deconvolution procedure.
      RESULTS: Plasma glucose followed the recognizable profiles, with oscillations
      closely linked to similar changes in the ISR. Pulse analysis of L-arginine
      profiles revealed significant oscillations linked to glucose and ISR
      oscillations, with the highest cross-correlation coefficients at time lag 0
      ranging from 0.380 to 0.680 for glucose and L-arginine and from 0.444 to 0.726
      for ISR and L-arginine (P < 0.01). The mean period of L-arginine oscillations was
      77.2 +/- 6.2 min, and their mean amplitude was 19.9 +/- 1.7%, similar to that of
      glucose (17.0 +/- 1.9%), when expressed as the percentage of mean overnight
      levels. CONCLUSIONS: This newly discovered ultradian rhythm of L-arginine and its
      coupling with glucose and ISR oscillations sheds new light on the regulation of L
      arginine, the substrate of numerous metabolic pathways, including nitric oxide
      synthesis. These oscillations may be of significance in conditions of
      hyperinsulinemia or abnormal glucose tolerance.

PMID- 12502676
TI  - Rosiglitazone improves insulin sensitivity and lowers blood pressure in
      hypertensive patients.
AB  - OBJECTIVE: To examine the effect of rosiglitazone on insulin resistance and blood
      pressure in patients with essential hypertension, classified based on
      abnormalities of their renin-angiotensin system. RESEARCH DESIGN AND METHODS: A
      total of 24 hypertensive nondiabetic patients (age 58 +/- 6 years, BMI 30 +/- 5
      kg/m2) were studied before and after rosiglitazone treatment. After 2 weeks off
      antihypertensive medication, subjects received a euglycemic-hyperinsulinemic
      clamp (40 mU. m(-2). min(-1)) with 6,6-[2H2]glucose infusion, ambulatory blood
      pressure monitoring, and blood tests for cardiovascular risk factors. Subjects
      were then placed on rosiglitazone (4 mg orally b.i.d.) and their usual
      antihypertensive medications (but not ACE inhibitors) for 16 weeks, and baseline
      tests were repeated. RESULTS: There was no change in fasting plasma glucose (83
      +/- 2 vs. 82 +/- 2 mg/dl, P = 0.60), but fasting insulin decreased (16.1 +/- 1.4
      vs. 12.5 +/- 0.9 micro U/ml, P < 0.01). Total glucose disposal during the clamp
      increased (5.0 +/- 0.4 vs. 5.9 +/- 0.5 mg. kg(-1). min(-1), P < 0.001), with no
      change in suppression of hepatic glucose output. There were significant decreases
      in mean 24-h systolic (138 +/- 2 vs. 134 +/- 2 mmHg, P < 0.02) and diastolic (85
      +/- 2 vs. 80 +/- 2 mmHg, P < 0.0001) blood pressure, and the decline in systolic
      blood pressure was correlated with the improvement in insulin sensitivity (r =
      0.59, P < 0.005). Triglycerides (135 +/- 16 vs. 89 +/- 8 mg/dl, P < 0.01), LDL
      cholesterol (129 +/- 6 vs. 122 +/- 8 mg/dl, P = 0.18), and HDL cholesterol (51 +/
      3 vs. 46 +/- 3 mg/dl, P < 0.02) all decreased, with no change in the LDL-to-HDL
      ratio. Plasminogen activator inhibitor-1 and C-reactive protein also declined
      significantly. CONCLUSIONS: Rosiglitazone treatment of nondiabetic hypertensive
      patients improves insulin sensitivity, reduces systolic and diastolic blood
      pressure, and induces favorable changes in markers of cardiovascular risk.
      Insulin sensitizers may provide cardiovascular benefits when used in the
      treatment of patients with hypertension.

PMID- 12502677
TI  - Promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene
      of human phosphatidylinositol 3-kinase are not associated with insulin secretion
      or insulin sensitivity in finnish subjects.
AB  - OBJECTIVE: Phosphatidylinositol (PI) 3-kinase activity is required for insulin
      stimulated translocation of GLUT4 transporters and glucose uptake and
      utilization. Therefore, genes encoding the subunits of PI 3-kinase are promising
      candidate genes for insulin resistance and type 2 diabetes. We recently cloned
      the catalytic subunit p110beta gene of human PI 3-kinase and reported two
      nucleotide polymorphisms, -359T/C and -303A/G, in the promoter region of this
      gene. In this study, we determined the effects of these polymorphisms on insulin
      secretion and insulin sensitivity. RESEARCH DESIGN AND METHODS: We studied two
      separate groups of Finnish nondiabetic subjects. Insulin secretion was evaluated
      by intravenous glucose tolerance test and insulin sensitivity by hyperinsulinemic
      euglycemic clamp. RESULTS: Our results showed that the -359T/C and -303A/G
      polymorphisms did not have a significant effect on fasting plasma insulin levels,
      insulin secretion, or insulin sensitivity. CONCLUSIONS: It is unlikely that the
      promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene
      of human PI 3-kinase have a major impact on insulin secretion, insulin
      sensitivity, or the risk of type 2 diabetes in Finnish subjects.

PMID- 12502678
TI  - Comparison of an insulin analog, insulin aspart, and regular human insulin with
      no insulin in gestational diabetes mellitus.
AB  - OBJECTIVE: To assess the short-term efficacy of insulin aspart in comparison with
      regular human insulin in women with gestational diabetes mellitus (GDM) during
      standardized meal tests. RESEARCH DESIGN AND METHODS: The study included 15 women
      with GDM who had inadequate diabetes control with diet alone. On 3 consecutive
      days, breakfast meal tests were performed-the first with no exogenous insulin and
      the other two after the injection of either regular insulin or insulin aspart.
      RESULTS: The peak insulin concentration was higher and the peak glucose and C
      peptide concentrations were lower with both insulin preparations than with no
      exogenous insulin. Glucose areas under the curve above baseline were
      significantly lower with insulin aspart (180-min area, 7.1 mg. h. dl(-1); P =
      0.018), but not with regular insulin (30.2 mg. h. dl(-1); P = 0.997), than with
      no insulin (29.4 mg. h. dl(-1)). CONCLUSIONS: This study demonstrates that
      effective postprandial glycemic control in women with GDM who required insulin
      was brought about by insulin aspart through higher insulin peak and lower demand
      on endogenous insulin secretion.

PMID- 12502679
TI  - Relation of birth weight to fasting insulin, insulin resistance, and body size in
      adolescence.
AB  - OBJECTIVE: A relationship between birth weight and the insulin resistance
      syndrome has been reported in adults but has not been defined in adolescents.
      RESEARCH DESIGN AND METHODS: Data were analyzed in 296 children (132 girls and
      164 boys) mean age 15.0 +/- 1.2 years who had euglycemic insulin clamp studies
      (intravenous administration of 1 mU. kg(-1). min(-1) of insulin balanced by a
      variable infusion of 20% glucose to maintain blood glucose at 100 mg/dl). Insulin
      sensitivity (M(LBM)) was determined by glucose uptake per kg lean body mass
      (LBM), and parents reported birth weight. RESULTS: Birth weight ranged from 1,021
      to 4,848 g (mean +/- SD 3,433 +/- 551), with 4.0% <2,500 g. Fat mass and BMI had
      U-shaped relations with birth weight after adjustment for race, age, sex, and
      blood pressure. Lean mass index (lean mass/height squared) was stable across
      birth weight quartiles. Fasting insulin decreased nonsignificantly across birth
      weight quartiles but became significant after adjustment for adolescent weight (P
      = 0.008). Although M(LBM) was highest in the highest birth weight quartile, the
      pattern was not significant. Triglycerides tended to increase with birth weight,
      whereas LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) tended to decrease.
      Blood pressure was unrelated to birth weight. CONCLUSIONS: In this cohort, fat
      mass was greater in adolescents with low and high birth weight; fasting insulin
      was lower with higher birth weight after adjustment for adolescent weight.
      Insulin sensitivity increased nonsignificantly with birth weight.

PMID- 12502680
TI  - Determinants of fetal growth at different periods of pregnancies complicated by
      gestational diabetes mellitus or impaired glucose tolerance.
AB  - OBJECTIVE: To determine maternal parameters with the strongest influence on fetal
      growth in different periods of pregnancies complicated by an abnormal glucose
      tolerance test (GTT). RESEARCH DESIGN AND METHODS: Retrospective study of 368
      women with gestational diabetes mellitus (GDM; > or = 2 abnormal GTT values, n =
      280) and impaired glucose tolerance (IGT; one abnormal value, n = 88) with 869
      ultrasound examinations at entry to and during diabetic care. Both groups were
      managed comparably. Abdominal circumference (AC) > or = 90th percentile defined
      fetal macrosomia. Maternal historical and clinical parameters, and diagnostic and
      glycemic values of glucose profiles divided into five categories of 4 weeks of
      gestational age (GA; <24 weeks, 24 weeks/0 days to 27 weeks/6 days, 28/0-31/6,
      32/0-35/6, and 36/0-40/0 [referred to as <24 GA, 24 GA, 28 GA, 32 GA, and 36 GA
      categories, respectively]) were tested by univariate and multiple logistic
      regression analysis for their ability to predict an AC > or = 90th percentile at
      each GA group and large-for-gestational-age (LGA) newborn. Data obtained at entry
      were also analyzed separately irrespective of the GA. RESULTS: Maternal weight,
      glycemia after therapy, rates of fetal macrosomia, and LGA were not significantly
      different between GDM and IGT; thus, both groups were analyzed together. LGA in a
      previous pregnancy, (odds ratio [OR] 3.6; 95% CI 1.8-7.3) and prepregnancy
      obesity (BMI > or = 30 kg/m(2); 2.1; 1.2-3.7) independently predicted AC > or =
      90th percentile at entry. When data for each GA category were analyzed, no
      predictors were found for <24 GA. Independent predictors for each subsequent GA
      category were as follows: at 24 GA, LGA history (OR 9.8); at 28 GA, LGA history
      (OR 4.2), and obesity (OR 3.3); at 32 GA, fasting glucose of 32 GA (OR 1.6 per 5
      mg/dl increase); at 36 GA, fasting glucose of 32 GA (OR 1.6); and for LGA at
      birth, LGA history (OR 2.7), and obesity (OR 2.4). CONCLUSIONS: In the late
      second and early third trimester, maternal BMI and LGA in a previous pregnancy
      appear to have the strongest influence on fetal growth, while later in the third
      trimester coincident with the period of maximum growth described in diabetic
      pregnancies, maternal glycemia predominates.

PMID- 12502681
TI  - A cross-sectional study of the effects of type 2 diabetes and other
      cardiovascular risk factors on structure and function of nonstenotic arteries of
      the lower limb.
AB  - OBJECTIVE: To compare intimal-medial thickness (IMT) and pulse wave conduction
      velocity (PWCV) in unstenosed arteries of the lower limb in subjects with and
      without type 2 diabetes and to determine the contribution of a range of
      cardiovascular risk factors. RESEARCH DESIGN AND METHODS: IMT and PWCV were
      determined in lower-limb arteries of 79 subjects with diabetes and 77 euglycemic
      subjects. Plasma lipids were determined by enzymatic assays, and LDL particle
      size was measured by gradient gel electrophoresis. Lag time for copper-induced
      oxidation of LDL was determined. alpha-Tocopherol, retinol, and ascorbate levels
      were determined by high-performance liquid chromatography, soluble E-selectin by
      enzyme-linked immunosorbent assay, and fibrinogen and factor VII by automated
      assays. RESULTS: Subjects with diabetes had greater superficial femoral artery
      (SFA) IMT, popliteal artery (PA) IMT, and SFA PWCV (all P < 0.0001). In
      univariate analysis, IMT and PWCV correlated with increased waist-to-hip ratio,
      triglycerides, and fibrinogen and inversely with HDL cholesterol and LDL size.
      Ascorbate was inversely associated with IMT, and LDL lag time was inversely
      correlated with PWCV. Subjects with the greatest number of features of the
      metabolic syndrome had the highest IMT and PWCV. CONCLUSIONS: Adverse changes in
      the structure and function of unstenosed lower-limb arteries are present in type
      2 diabetes and are associated with features of the metabolic syndrome.

PMID- 12502682
TI  - Excess physical limitations among adults with diabetes in the U.S. population,
      1997-1999.
AB  - OBJECTIVE: To estimate the prevalence of physical limitations associated with
      diabetes among U.S. adults > or =18 years of age. RESEARCH DESIGN AND METHODS: We
      conducted a cross-sectional analysis of the association between diabetes status
      and physical limitations using the 1997-1999 National Health Interview Survey
      (NHIS). Physical limitation was defined from self-reported degree of difficulty
      with nine tasks. RESULTS: People with diabetes had a higher proportion of any
      physical limitation than did people without diabetes overall (66 vs. 29%, P <
      0.001), for both men (59 vs. 24%, P < 0.001) and women (72 vs. 34%, P < 0.001).
      Compared with those without diabetes, a higher proportion of people with diabetes
      had some physical limitation among all age groups, and the difference declined
      (all P < 0.001) with increasing age (46 vs. 18% for 18-44 years, 63 vs. 35% for
      45-64 years, 74 vs. 53% for 65-74 years, and 85 vs. 70% for those 75 years and
      older). After controlling for demographic characteristics and several other
      confounders, the odds ratio of physical limitation among adults with diabetes
      versus those without diabetes was 1.9 (95% CI: 1.8-2.1). CONCLUSIONS: People with
      diabetes are much more likely to have a physical limitation than those without
      diabetes. Interventions are needed in this population to reduce progression from
      impairment to physical limitation and from physical limitation to disability,
      especially because the prevalence of diabetes is projected to increase
      dramatically in the next several decades.

PMID- 12502683
TI  - Diabetic muscle infarction: an underdiagnosed complication of long-standing
      diabetes.
AB  - OBJECTIVE: To systematically review all the reported cases of diabetic muscle
      infarction (DMI) and its pathogenesis, clinical features, prognostic
      implications, and management. RESEARCH DESIGN AND METHODS: We searched databases
      (MEDLINE and EMBASE) from their inception to August 2001 and reviewed
      bibliographies in reports retrieved. Data were extracted in a standardized form.
      RESULTS: A total of 47 references were retrieved; 115 patients and 166 episodes
      were included. DMI was more frequent in women (61.5%, mean age at presentation
      42.6 years). Of the cases, 59% had type 1 diabetes; the mean duration of disease
      was 14.3 years, and multiple diabetic end-organ complications were noted. DMI
      affects the lower limbs with abrupt onset of pain and local swelling. Diagnosis
      is made by biopsy, but the characteristic features in magnetic resonance imaging
      are very typical. Treatment includes bed rest and administration of analgesics,
      but recurrence is common. CONCLUSIONS: DMI is a very uncommon complication of
      long-standing diabetes; presentation is well characterized and management is
      simple.

PMID- 12502684
TI  - Effects of injectable or implantable progestin-only contraceptives on insulin
      glucose metabolism and diabetes risk.
AB  - Progestin-only contraceptives administered by injection (Depo-Provera) or
      subcutaneous implant (Norplant) have been available to U.S. women for about a
      decade. Two epidemiological studies found their use associated with increased
      incidence of type 2 diabetes. In reviewing publications relating progestin
      injections and implants to glucose metabolism, 25 studies of various study
      designs and laboratory methods were identified that reported at least one insulin
      value in nondiabetic women. Research subjects were usually nonobese and often
      from developing countries. Of eight studies that performed sequential oral
      glucose tolerance tests (OGTTs) after at least 6 months of Depo-Provera or
      Norplant use, seven found significant elevations (approximate doubling) of
      insulin at 2 or 3 h after glucose challenge; the effects on fasting, half-hour,
      or 1-h postchallenge insulin values were less consistent. The three studies that
      performed sequential intravenous glucose tolerance tests (IVGTTs) on injection
      users all found an increased early-phase insulin response. One study used
      sequential hyperglycemic-hyperinsulinemic clamps to demonstrate reduced total
      body glucose uptake per unit of insulin after 8 weeks of Norplant use. The
      metabolic studies generally did not show a reduction in the glucose tolerance of
      their nondiabetic subjects. However, compared with the lean and low-risk women
      who were usually selected for metabolic research, many U.S. women receiving these
      injections or implants may start out with increased insulin resistance due to
      greater weight, sedentary lifestyle, and family or childbearing histories.
      Additional research could help clarify whether exposure to injectable or
      implantable contraceptives leads to increased risk of type 2 diabetes and
      gestational diabetes in women with predisposing factors.

PMID- 12502685
TI  - Diabetic retinopathy.

PMID- 12502686
TI  - Cardiovascular disease and diabetes.

PMID- 12502687
TI  - The cost of preventing diabetes: what do we know and what do we need to know?

PMID- 12502688
TI  - Non-HDL cholesterol: into the spotlight.

PMID- 12502689
TI  - Is metformin cardioprotective?

PMID- 12502690
TI  - Comparison of glycemic and lipid response to pioglitazone treatment in Mexican
      Americans and non-Hispanic Caucasians with type 2 diabetes.

PMID- 12502691
TI  - Diabetic vasculopathy and alcohol tolerance trait in type 2 diabetes.

PMID- 12502692
TI  - Indications that phototherapy is a risk factor for insulin-dependent diabetes.

PMID- 12502693
TI  - Screening using compressed digital retinal images successfully identifies
      retinopathy.

PMID- 12502694
TI  - Celiac disease and type 1 diabetes.

PMID- 12502695
TI  - Influence of alcohol intake and aldehyde dehydrogenase 2 phenotype on peripheral
      neuropathy of diabetes.

PMID- 12502696
TI  - High prevalence of insulin resistance and metabolic syndrome in overweight/obese
      preadolescent Hong Kong Chinese children aged 9-12 years.

PMID- 12502697
TI  - Relationship of beta2-adrenergic receptor polymorphism with obesity in type 2
      diabetes.

PMID- 12502698
TI  - Effect of structured group education on glycemic control and hypoglycemia in
      insulin-treated patients.

PMID- 12502699
TI  - Decreased glucagon-like peptide 1 fasting levels in type 2 diabetes.

PMID- 12502700
TI  - The human insulin analogue aspart is not the almighty solution for insulin
      allergy.

PMID- 12502701
TI  - Docosahexaenoic acid but not eicosapentaenoic acid increases LDL particle size in
      treated hypertensive type 2 diabetic patients.

PMID- 12502702
TI  - Intensive diabetes management may improve pregnancy: outcomes in Chinese gravidas
      with impaired glucose tolerance.

PMID- 12502703
TI  - Thyroid stimulating hormone screening is more sensitive for detecting thyroid
      abnormalities in children and adolescents with type 1 diabetes.

PMID- 12502705
TI  - Reproducibility of the continuous glucose monitoring system matches previous
      reports and the intended use of the product.

PMID- 12502707
TI  - Identification and molecular characterization of a chitinase from the hard tick
      Haemaphysalis longicornis.
AB  - A cDNA encoding tick chitinase was cloned from a cDNA library of mRNA from
      Haemaphysalis longicornis eggs and designated as CHT1 cDNA. The CHT1 cDNA
      contains an open reading frame of 2790 bp that codes for 930 amino acid residues
      with a coding capacity of 104 kDa. The deduced amino acid sequence shows a 31%
      amino acid homology to Aedes aegypti chitinase and a multidomain structure
      containing one chitin binding peritrophin A domain and two glycosyl hydrolase
      family 18 chitin binding domains. The endogenous chitinase of H. longicornis was
      identified by a two-dimensional immunoblot analysis with mouse anti-rCHT1 serum
      and shown to have a molecular mass of 108 kDa with a pI of 5.0. A recombinant
      baculovirus AcMNPV.CHT1-expressed rCHT1 is glycosylated and able to degrade
      chitin. Chitin degradation was ablated by allosamidin in a dose-dependent manner.
      The optimal temperature and pH for activity of the purified chitinase were 45
      degrees C and pH 5-7. The CHT1 cDNA has an ELR motif for chemokine-mediated
      angiogenesis and appears to be a chitinase of the chemokine family. Localization
      analysis using mouse anti-rCHT1 serum revealed that native chitinase is highly
      expressed in the epidermis and midgut of the tick. AcMNPV.CHT1 topically applied
      to H. longicornis ticks exhibited replication. This is the first report of insect
      baculovirus infection of ticks. The importance of AcMNPV.CHT1 as a novel bio
      acaricide for tick control is discussed.

PMID- 12502708
TI  - Role of reduced glutathione efflux in apoptosis of immortalized human
      keratinocytes induced by UVA.
AB  - We have investigated the role played by GSH efflux in apoptosis of human HaCaT
      keratinocytes induced by UVA irradiation. UVA irradiation of HaCaT cells caused a
      rapid rise in GSH efflux across the intact cell membrane, followed by an increase
      in apoptosis. GSH efflux was stimulated by glucose and was reduced by the
      addition of exogenous GSH and intracellular GSH depletion by buthionine
      sulfoximine, suggesting that GSH transport is active and is influenced by the GSH
      concentration gradient across the cell membrane. Verapamil and cyclosporin A,
      blockers of the multidrug resistance-associated protein, decreased UVA-induced
      GSH efflux. GSH efflux occurred within 2 h of UVA irradiation, suggesting that
      the stimulation of GSH efflux is due to an increase in the activity of pre
      existing multidrug resistance-associated protein transporter carrier. Although
      inhibition of GSH efflux did not affect caspase activation and DNA fragmentation,
      it delayed the gradual increase in plasma membrane permeability and reduced
      phosphatidylserine translocation in HaCaT cells. It is therefore likely that upon
      UVA irradiation, GSH efflux increased the intracellular oxidative stress without
      intervention of reactive oxygen species, thus resulting in more
      phosphatidylserine externalization and membrane rearrangement. These provide
      targets for macrophage recognition and phagocytosis and thus minimize the
      potential to invoke inflammation or neoplastic transformation.

PMID- 12502709
TI  - A synthetic peptide ligand of neural cell adhesion molecule (NCAM), C3d, promotes
      neuritogenesis and synaptogenesis and modulates presynaptic function in primary
      cultures of rat hippocampal neurons.
AB  - The neural cell adhesion molecule (NCAM) plays a key role in morphogenesis of the
      nervous system and in remodeling of neuronal connections accompanying
      regenerative and cognitive processes. Recently, a new synthetic ligand of NCAM,
      the C3-peptide, which binds to the NCAM IgI module, has been identified by means
      of combinatorial chemistry (Ronn, L. C. B, Olsen, M., Ostergaard, S., Kiselyov,
      V., Berezin, V., Mortensen, M. T., Lerche, M. H., Jensen, P. H., Soroka, V.,
      Saffell, J. L., Doherty, P., Poulsen, F. M., Bock, E., Holm, A., and Saffells, J.
      L. (1999) Nat. Biotechnol. 17, 1000-1005). In vitro, the dendrimeric form of C3,
      termed C3d, disrupts NCAM-mediated cell adhesion, induces neurite outgrowth, and
      triggers intracellular signaling cascades similar to those activated by
      homophilic NCAM binding. The peptide may therefore be expected to regulate
      regeneration and synaptic plasticity. Here we demonstrate that in primary
      cultures of hippocampal neurons: 1) C3d induces a sustained neuritogenic
      response, the neuritogenic activity of the compound being dependent on the dose,
      starting time, and duration of peptide application; 2) the peptide triggers the
      neuritogenic response by forming an adhesive substratum necessary for NCAM
      mediated neurite formation and elongation; 3) C3d promotes synapse formation; and
      4) C3d modulates the presynaptic function, causing a transient increase of the
      function at low (2 and 5 microm) doses and a reduction when applied at a higher
      concentration (10 microm). The effect of the peptide is dependent on the
      activation of the fibroblast growth factor receptor. We suggest that C3d may
      constitute a useful lead for the development of compounds for treatment of
      various neurodegenerative disorders.

PMID- 12502710
TI  - 1,N2-deoxyguanosine adducts of acrolein, crotonaldehyde, and trans-4
      hydroxynonenal cross-link to peptides via Schiff base linkage.
AB  - DNA-protein cross-links (DPCs) are formed upon exposure to a variety of chemical
      and physical agents and pose a threat to genomic integrity. In particular,
      acrolein and related aldehydes produce DPCs, although the chemical linkages for
      such cross-links have not been identified. Here, we report that
      oligodeoxynucleotides containing 1,N(2)-deoxyguanosine adducts of acrolein,
      crotonaldehyde, and trans-4-hydroxynonenal can form cross-links with the
      tetrapeptide Lys-Trp-Lys-Lys. We concluded that complex formation is mediated by
      a Schiff base linkage because DNA-peptide complexes were covalently trapped
      following reduction with sodium cyanoborohydride, and pre-reduction of adducted
      DNAs inhibited complex formation. A previous NMR study demonstrated that duplex
      DNA catalyzes ring opening for the acrolein-derived gamma-hydroxy-1,N(2)
      propanodeoxyguanosine adduct to yield an aldehydic function (de los Santos, C.,
      Zaliznyak, T., and Johnson, F. (2001) J. Biol. Chem. 276, 9077-9082). Consistent
      with this earlier observation, the adducts under investigation were more reactive
      in duplex DNA than in single-stranded DNA, and we concluded that the ring-open
      aldehydic moiety is the induced tautomer in duplex DNA for adducts exhibiting
      high relative reactivity. Adducted DNA cross-linked to Arg-Trp-Arg-Arg and Lys
      Trp-Lys-Lys with comparable efficiency, and N(alpha)-acetylation of peptides
      dramatically inhibited trapping; thus, the reactive nucleophile is located at the
      N-terminal alpha-amine of the peptide. These data suggest that Schiff base
      chemistry can mediate DPC formation in vivo following the formation of stable
      aldehyde-derived DNA adducts.

PMID- 12502711
TI  - The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in
      hepatic stellate cell proliferation and type I collagen expression.
AB  - Following a fibrogenic stimulus, the hepatic stellate cell (HSC) undergoes a
      complex activation process associated with increased cell proliferation and
      excess deposition of type I collagen. The focal adhesion kinase (FAK)
      phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is activated by
      platelet-derived growth factor (PDGF) in several cell types. We investigated the
      role of the FAK-PI3K-Akt pathway in HSC activation. Inhibition of FAK activity
      blocked HSC migration, cell attachment, and PDGF-induced PI3K and Akt activation.
      Both serum- and PDGF-induced Akt phosphorylation was inhibited by LY294002, an
      inhibitor of PI3K. A constitutively active form of Akt stimulated HSC
      proliferation in serum-starved HSCs, whereas LY294002 and dominant-negative forms
      of Akt and FAK inhibited PDGF-induced proliferation. Transforming growth factor
      beta, an inhibitor of HSC proliferation, did not block PDGF-induced Akt
      phosphorylation, suggesting that transforming growth factor-beta mediates its
      antiproliferative effect downstream of Akt. Expression of type I collagen protein
      and alpha1(I) collagen mRNA was increased by Akt activation and inhibited when
      PI3K activity was blocked. Therefore, FAK is important for HSC migration, cell
      attachment, and PDGF-induced cell proliferation. PI3K is positioned downstream of
      FAK. Signals for HSC proliferation are transduced through FAK, PI3K, and Akt.
      Finally, expression of type I collagen is regulated by the PI3K-Akt signaling
      pathway.

PMID- 12502712
TI  - Insertion of Pex5p into the peroxisomal membrane is cargo protein-dependent.
AB  - It is now generally accepted that Pex5p, the receptor for most peroxisomal matrix
      proteins, cycles between the cytosol and the peroxisomal compartment. According
      to current models of peroxisomal biogenesis, this intracellular trafficking of
      Pex5p is coupled to the transport of newly synthesized peroxisomal proteins into
      the organelle matrix. However, direct evidence supporting this hypothesis was
      never provided. Here, using an in vitro peroxisomal import system, we show that
      insertion of Pex5p into the peroxisomal membrane requires the presence of cargo
      proteins. Strikingly the peroxisomal docking/translocation machinery is also able
      to catalyze the membrane insertion of a Pex5p truncated molecule lacking any
      known cargo-binding domain. These results suggest that the cytosol/peroxisomal
      cycle in which Pex5p is involved is directly or indirectly regulated by Pex5p
      itself and not by the peroxisomal docking/translocation machinery.

PMID- 12502713
TI  - The FAR protein family of the nematode Caenorhabditis elegans. Differential lipid
      binding properties, structural characteristics, and developmental regulation.
AB  - Parasitic nematodes of humans and plants secrete a structurally novel type of
      fatty acid- and retinol-binding protein, FAR, into the tissues they occupy. These
      proteins may interfere with intercellular lipid signaling to manipulate the
      defense reactions of the host or acquire essential lipids for the parasites. The
      genome of the nematode Caenorhabditis elegans encodes eight FAR-like proteins (Ce
      FAR-1 to -8). These fall into three discrete groups as indicated by phylogenetic
      sequence comparisons and intron positions, the proteins from parasitic nematodes
      falling into group A. Recombinant Ce-FAR-1 to -7 were produced in Escherichia
      coli and tested for lipid binding in fluorescence-based assays. Ce-FAR-1 to -6
      bound DAUDA (11-((5-dimethylaminonaphthalene-1-sulfonyl)amino)undecanoic acid),
      cis-parinaric acid, and retinol with dissociation constants in the micromolar
      range, whereas Ce-FAR-7 bound the latter two lipids relatively poorly. Each
      protein produced a characteristic shift in peak fluorescence emission of DAUDA,
      and one (Ce-FAR-5) produced a shift greater than has been observed previously for
      any lipid-binding protein. Selected Ce-FAR proteins were analyzed by circular
      dichroism (CD) and differential scanning calorimetry, were found to be helix
      rich, and exhibited high thermal stability (transition midpoint, 82.7 degrees C).
      CD and secondary structure predictions, however, both indicated that Ce-FAR-7
      possesses substantially less helix than the other FAR proteins. The genes
      encoding the Ce-FAR proteins were found to be transcribed differentially through
      the life cycle of C. elegans, such that Ce-far-4 was transcribed at highest
      levels in the fourth larval stage, and Ce-far-3 and -7 predominated in males.

PMID- 12502714
TI  - Identification and characterization of the autophosphorylation sites of
      phosphoinositide 3-kinase isoforms beta and gamma.
AB  - Class I phosphoinositide 3-kinases (PI3Ks) are bifunctional enzymes possessing
      lipid kinase activity and the capacity to phosphorylate their catalytic and/or
      regulatory subunits. In this study, in vitro autophosphorylation of the G protein
      sensitive p85-coupled class I(A) PI3K beta and p101-coupled class I(B) PI3K gamma
      was examined. Autophosphorylation sites of both PI3K isoforms were mapped to C
      terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110
      beta and serine 1101 of p110 gamma). Like other class I(A) PI3K isoforms,
      autophosphorylation of p110 beta resulted in down-regulated PI3K beta lipid
      kinase activity. However, no inhibitory effect of p110 gamma autophosphorylation
      on PI3K gamma lipid kinase activity was observed. Moreover, PI3K beta and PI3K
      gamma differed in the regulation of their autophosphorylation. Whereas p110 beta
      autophosphorylation was stimulated neither by G beta gamma complexes nor by a
      phosphotyrosyl peptide derived from the platelet-derived growth factor receptor,
      autophosphorylation of p110 gamma was significantly enhanced by G beta gamma in a
      time- and concentration-dependent manner. In summary, we show that
      autophosphorylation of both PI3K beta and PI3K gamma occurs in a C-terminal
      region of the catalytic p110 subunit but differs in its regulation and possible
      functional consequences, suggesting distinct roles of autophosphorylation of PI3K
      beta and PI3K gamma.

PMID- 12502715
TI  - A novel bifunctional wax ester synthase/acyl-CoA:diacylglycerol acyltransferase
      mediates wax ester and triacylglycerol biosynthesis in Acinetobacter
      calcoaceticus ADP1.
AB  - Triacylglycerols (TAGs) and wax esters are neutral lipids with considerable
      importance for dietetic, technical, cosmetic, and pharmaceutical applications.
      Acinetobacter calcoaceticus ADP1 accumulates wax esters and TAGs as intracellular
      storage lipids. We describe here the identification of a bifunctional enzyme from
      this bacterium exhibiting acyl-CoA:fatty alcohol acyltransferase (wax ester
      synthase, WS) as well as acyl-CoA:diacylglycerol acyltransferase (DGAT) activity.
      Experiments with a knock-out mutant demonstrated the key role of the bifunctional
      WS/DGAT for biosynthesis of both storage lipids in A. calcoaceticus. This novel
      type of long-chain acyl-CoA acyltransferase is not related to known
      acyltransferases including the WS from jojoba (Simmondsia chinensis), the DGAT1
      or DGAT2 families present in yeast, plants, and animals, and the
      phospholipid:diacylglycerol acyltransferase catalyzing TAG formation in yeast and
      plants. A large number of WS/DGAT-related proteins were identified in
      Mycobacterium and Arabidopsis thaliana indicating an important function of these
      proteins. WS and DGAT activity was demonstrated for the translational product of
      one WS/DGAT homologous gene from M. smegmatis mc(2)155. The potential of WS/DGAT
      to establish novel processes for biotechnological production of jojoba-like wax
      esters was demonstrated by heterologous expression in recombinant Pseudomonas
      citronellolis. The potential of WS/DGAT as a selective therapeutic target of
      mycobacterial infections is discussed.

PMID- 12502716
TI  - Ligand and coactivator identity determines the requirement of the charge clamp
      for coactivation of the peroxisome proliferator-activated receptor gamma.
AB  - The activation function 2 (AF-2)-dependent recruitment of coactivator is
      essential for gene activation by nuclear receptors. We show that the peroxisome
      proliferator-activated receptor gamma (PPARgamma) (NR1C3) coactivator-1 (PGC-1)
      requires both the intact AF-2 domain of PPARgamma and the LXXLL domain of PGC-1
      for ligand-dependent and ligand-independent interaction and coactivation.
      Although the AF-2 domain of PPARgamma is absolutely required for PGC-1-mediated
      coactivation, this coactivator displayed a unique lack of requirement for the
      charge clamp of the ligand-binding domain of the receptor that is thought to be
      essential for LXXLL motif recognition. The mutation of a single serine residue
      adjacent to the core LXXLL motif of PGC-1 led to restoration of the typical
      charge clamp requirement. Thus, the unique structural features of the PGC-1 LXXLL
      motif appear to mediate an atypical mode of interaction with PPARgamma.
      Unexpectedly, we discovered that various ligands display variability in terms of
      their requirement for the charge clamp of PPARgamma for coactivation by PGC-1.
      This ligand-selective variable requirement for the charge clamp was coactivator
      specific. Thus, distinct structural determinants, which may be unique for a
      particular ligand, are utilized by the receptor to recognize the coactivator. Our
      data suggest that even subtle differences in ligand structure are perceived by
      the receptor and translated into a unique display of the coactivator-binding
      surface of the ligand-binding domain, allowing for differential recognition of
      coactivators that may underlie distinct pharmacological profiles observed for
      ligands of a particular nuclear receptor.

PMID- 12502717
TI  - Human group IVC phospholipase A2 (cPLA2gamma). Roles in the membrane remodeling
      and activation induced by oxidative stress.
AB  - To create the unique properties of a certain cellular membrane, both the
      composition and the metabolism of membrane phospholipids are key factors.
      Phospholipase A(2) (PLA(2)), with hydrolytic enzyme activities at the sn-2
      position in glycerophospholipids, plays critical roles in maintaining the
      phospholipid composition as well as producing bioactive lipid mediators. In this
      study we examined the contribution of a Ca(2+)-independent group IVC PLA(2)
      isozyme (cPLA(2)gamma), a paralogue of cytosolic PLA(2)alpha (cPLA(2)alpha), to
      phospholipid remodeling. The enzyme was localized in the endoplasmic reticulum
      and Golgi apparatus, as seen using green fluorescence fusion proteins.
      Electrospray ionization mass spectrometric analysis of membrane extracts revealed
      that overexpression of cPLA(2)gamma increased the proportion of polyunsaturated
      fatty acids in phosphatidylethanolamine, suggesting that the enzyme modulates the
      phospholipid composition. We also found that H(2)O(2) and other hydroperoxides
      induced arachidonic acid release in cPLA(2)gamma-transfected human embryonic
      kidney 293 cells, possibly through the tyrosine phosphorylation pathway. Thus, we
      propose that cPLA(2)gamma is constitutively expressed in the endoplasmic
      reticulum and plays important roles in remodeling and maintaining membrane
      phospholipids under various conditions, including oxidative stress.

PMID- 12502718
TI  - Gene-engineered rigidification of membrane lipids enhances the cold inducibility
      of gene expression in synechocystis.
AB  - A sudden decrease in ambient temperature induces the expression of a number of
      genes in poikilothermic organisms. We report here that the cold inducibility of
      gene expression in Synechocystis sp. PCC 6803 was enhanced by the rigidification
      of membrane lipids that was engineered by disruption of genes for fatty acid
      desaturases. DNA microarray analysis revealed that cold-inducible genes could be
      divided into three groups according to the effects of the rigidification of
      membrane lipids. The first group included genes whose expression was not induced
      by cold in wild-type cells but became strongly cold-inducible upon rigidification
      of membrane lipids. This group included certain heat-shock genes, genes for
      subunits of the sulfate transport system, and the hik34 gene for a histidine
      kinase. The second group consisted of genes whose cold inducibility was
      moderately enhanced by the rigidification of membrane lipids. Most genes in this
      group encoded proteins of as yet unknown function. The third group consisted of
      genes whose cold inducibility was unaffected by the rigidification of membrane
      lipids. This group included genes for an RNA helicase and an RNA-binding protein.
      DNA microarray analysis also indicated that the rigidification of membrane lipids
      had no effect on the heat inducibility of gene expression. Hik33, a cold-sensing
      histidine kinase, regulated the expression of most genes in the second and third
      groups but of only a small number of genes in the first group, an observation
      that suggests that the cold-inducible expression of genes in the first group
      might be regulated by a cold sensor that remains to be identified.

PMID- 12502719
TI  - The mmaA2 gene of Mycobacterium tuberculosis encodes the distal cyclopropane
      synthase of the alpha-mycolic acid.
AB  - Infection with Mycobacterium tuberculosis (Mtb) remains a severe global health
      problem that has prompted an aggressive search for new antibiotic targets and
      vaccine strategies for this persistent pathogen. Recently, a wide variety of
      genetic determinants of Mtb pathogenicity have been identified, including several
      genes involved in the biogenesis of the complex Mtb cell envelope. Among these
      are the mycolic acid cyclopropane synthases, a family of proteins that modify the
      major cell envelope lipids of Mtb with a diversity of cyclopropane rings. Despite
      substantial sequence identity, these proteins catalyze highly specific
      cyclopropane modifications, including proximal modification of the alpha-mycolate
      (pcaA) and trans-cyclopropane modification (cmaA2). Here we report the mycolic
      acid modification function of a third cyclopropane synthase, mmaA2, through the
      creation and analysis of an M. tuberculosis mmaA2 null mutant. Unexpectedly,
      mmaA2 is essential for the distal cyclopropane modification of the alpha
      mycolate, a function previously attributed to cmaA1. alpha-Mycolates of a cmaA1
      null mutant were unaffected, demonstrating that cmaA1 is not required for alpha
      mycolate modification. Although fully cyclopropanated methoxymycolates are
      produced in the mmaA2 mutant, cis-cyclopropanation is impaired, leading to
      accumulation of unsaturated methoxymycolate derivatives. This study establishes
      mmaA2 as a distal cyclopropane synthase of the alpha-mycolates of M. tuberculosis
      and the first cyclopropane synthase to modify both alpha- and oxygenated
      mycolates. These results expand our knowledge of the biosynthesis of the Mtb cell
      envelope and will allow further elucidation of the relationship between Mtb
      pathogenesis and the fine structure of mycolic acids.

PMID- 12502720
TI  - Development of Th1 and not Th2 immune responses in mice lacking IFN-regulatory
      factor-4.
AB  - IFN-regulatory factor (IRF)-4 is a member of the IRF family of transcription
      factors expressed in lymphocytes and macrophages. The previous studies using mice
      deficient in the IRF-4 gene showed profound defects in function of both B and T
      cells. To further investigate the role of IRF-4 in CD4(+) T cell function, IRF-4(
      /-) mice were challenged with the intracellular pathogen Leishmania major. The
      mice were protected against L. major during the early phase of the infection and
      CD4(+) T cells of the infected mice produced IFN-gamma in response to L. major
      antigen. However, during the late phase of infection, lymphocyte numbers were
      dramatically reduced in the draining lymph nodes, resulting in the deterioration
      of the lesion, indicating that IRF-4 was required for sustained immune responses
      against L. major infection. The function of CD4(+) T cells was further
      investigated using TCR transgenic mice lacking the IRF-4 gene. CD4(+) T cells
      from IRF-4(-/-) mice produced IFN-gamma and expressed T-bet after culture under
      T(h)1-skewing conditions in vitro. However, T(h)2 cell development was not
      observed after culture under T(h)2-polarizing conditions. Proliferation of CD4(+)
      T cells to IL-4 was reduced in IRF-4(-/-) mice, suggesting the defects in the
      responsiveness to IL-4. Furthermore, stimulation of the IRF-4(-/-) CD4(+) T cells
      with IL-4-induced activation of signal transducer and activator of transcription
      6, but not expression of growth factor independent-1. Thus, development of CD4(+)
      T cell subsets differentially depends on IRF-4; induction of T(h)1 response does
      not depend on IRF-4, while T(h)2 response depends entirely on IRF-4.

PMID- 12502721
TI  - Experimental autoimmune myasthenia gravis in naive non-obese diabetic (NOD/LtJ)
      mice: susceptibility associated with natural IgG antibodies to the acetylcholine
      receptor.
AB  - Naive non-obese diabetic (NOD/LtJ) mice spontaneously produce natural IgG
      autoantibodies against self-antigens associated with the experimental autoimmune
      diseases to which they are susceptible: insulin-dependant diabetes mellitus,
      systemic lupus erythematosus and experimental autoimmune encephalomyelitis. We
      discovered recently that NOD/LtJ mice also spontaneously produce IgG antibodies
      to the acetylcholine receptor (AchR), an antigen that can induce experimental
      autoimmune myasthenia gravis (EAMG) in susceptible rodents. However, there are no
      reports indicating that NOD/LtJ mice are susceptible to EAMG. To test whether the
      presence of spontaneous IgG autoantibodies can predict susceptibility to an
      autoimmune disease, we challenged NOD/LtJ mice using a standard protocol to
      induce EAMG. We now report that NOD/LtJ mice developed EAMG, although to a
      somewhat lesser degree than did C57BL/6 mice, a strain regarded as highly
      susceptible to the disease. Both strains produced comparable levels of immune
      antibodies to AchR of the complement-fixing isotypes IgG2a and IgG2b; however,
      NOD/LtJ mice produced significantly more IgG1. An antigen-specific T cell
      proliferative response to AchR of the same magnitude was detected in both
      strains, together with the secretion of similar amounts of IFN-gamma. Thus,
      NOD/LtJ mice are susceptible to EAMG and disease induction is accompanied by
      immune responses comparable to those seen in the susceptible strain C57BL/6.
      These results support the association between specific, natural IgG
      autoantibodies and susceptibility to the induction of a particular autoimmune
      disease.

PMID- 12502722
TI  - Gamma-glutamyl transpeptidase activity alters the T cell response to oxidative
      stress and Fas-induced apoptosis.
AB  - The ectoenzyme gamma-glutamyl transpeptidase (GGT) is absent on resting naive
      peripheral blood T cells, highly expressed upon stimulation and intermediate on
      resting memory T cells. In other tissues, GGT is essential for the recapture of
      the antioxidant glutathione (GSH). T cells with different levels of GGT activity
      were examined for their ability to withstand oxidative stress. To create a model
      system that reflected the level of GGT seen on naive and memory T cells, Jurkat T
      cells were cloned by limiting dilution and their GGT expression analyzed. Jurkat
      expressing GGT at levels comparable to resting memory T cells have levels of
      intracellular reactive oxygen species (ROS) that are only 65% that seen in Jurkat
      that have low levels of GGT (similar to naive T cells). Treatment of the cells
      with H(2)O(2) increases ROS in both cells, although the level seen in the
      GGT(high) Jurkat is less than half that in the GGT(low) variant. Despite
      protection from oxidative stress, the GGT(high) Jurkat were found to be 2- to 3
      fold more sensitive to Fas-induced apoptosis. The redox-regulated NF-kappaB
      pathway is activated in GGT(low) cells, resulting in higher levels of cIAP-1/2
      proteins that limit caspase activity. The GGT(low) cells were found to have
      higher levels of NF-kappaB in the nucleus as well as lower levels of IkappaB
      alpha. The GGT(low) cells also express higher levels of the caspase inhibitors
      cIAP-1/2 and have lower levels of caspase activity. These findings suggest that
      GGT expression regulates ROS in T lymphocytes and modulates Fas-induced killing
      by altering NF-kappaB activity.

PMID- 12502723
TI  - Heterologous desensitization of T cell functions by CCR5 and CXCR4 ligands:
      inhibition of cellular signaling, adhesion and chemotaxis.
AB  - T cells migrate into inflamed sites through the extracellular matrix (ECM) in
      response to chemotactic areas and are then simultaneously or sequentially exposed
      to multiple chemotactic ligands. We examined the responses of human peripheral
      blood T cells, present in an ECM-like context, to combinatorial signaling
      transduced by SDF-1alpha (CXCL12), and two CCR5 ligands, RANTES (CCL5) and MIP
      1beta (CCL4). Separately, these chemokines, at G protein-coupled receptor (GPCR)
      stimulating concentrations, induced T cell adhesion to fibronectin (FN) and T
      cell chemotaxis. However, the pro-adhesive and pro-migratory capacities of SDF
      1alpha and RANTES or MIP-1beta were mutually suppressed by the simultaneous or
      sequential exposure of the cells to these CCR5 or CXCR4 ligands. This cross-talk
      did not involve the internalization of the SDF-1alpha receptor, CXCR4, but
      rather, a decrease in phosphorylation of ERK and Pyk-2, as well as inhibition of
      Ca(2+) mobilization. Strikingly, early CXCR4 signaling of phosphatidylinositol-3
      kinase, detected by SDF-1alpha-induced AKT phosphorylation, was insensitive to
      RANTES-CCR5 signals. Accordingly, early chemotaxis to SDF-1alpha was not
      susceptible to CCR5 occupancy, whereas late stages of T cell chemotaxis were
      markedly down-regulated. This is an example of a specialized functional
      desensitization of heterologous chemokine receptors that induces GPCR
      interference with T cell adhesion to ECM ligands and chemotaxis within chemokine
      rich extravascular contexts.

PMID- 12502724
TI  - The role of anti-HSP70 autoantibody-forming V(H)1-J(H)1 B-1 cells in Toxoplasma
      gondii-infected mice.
AB  - Anti-heat shock protein 70 (HSP70) autoantibody formation was induced by B-1
      cells (CD5(+) B cells) in Toxoplasma gondii-infected mice. Here we report that
      V(H)1-J(H)1 B-1 cells from peritoneal exudate cells (PEC) of T. gondii-infected
      C57BL/6 mice (B6, a susceptible strain) increased predominantly. Moreover, the
      hybridoma lines producing anti-T. gondii HSP70 (TgHSP70) antibody cross-reactive
      with mouse HSP70 (mHSP70) expressed the V(H)1-J(H)1 gene, whereas the hybridoma
      lines producing anti-TgHSP70 antibody non-cross-reactive with mHSP70 expressed
      the V(H)11A-J(H)1 gene or V(H)12-J(H)1 gene. The avidity maturation of anti
      TgHSP70 IgG antibody in the sera of BALB/c mice (a resistant strain) and that of
      anti-mHSP70 IgG autoantibody in the sera of B6 mice were observed 9 weeks after
      T. gondii infection. T. gondii numbers in the brains of T. gondii-infected B6
      mice treated with anti-mHSP70 autoantibody were markedly higher than those in the
      brains of T. gondii-infected B6 mice treated with anti-TgHSP70 antibody.
      Furthermore, B-1 cells producing IL-10 down-regulated the IFN-gamma expression of
      PEC in T. gondii-infected mice. These results indicate that B-1 cells dominantly
      expressing V(H)1-J(H)1 mRNA, and producing anti-HSP70 autoantibody and IL-10
      regulate susceptibility of mice to T. gondii infection.

PMID- 12502725
TI  - IL-15 enhances the function and inhibits CD95/Fas-induced apoptosis of human CD4+
      and CD8+ effector-memory T cells.
AB  - Although the effect of IL-15 has been described on murine cells in vitro and in
      vivo, its effect on human memory CD8(+) T cells is not well characterized. We
      show here that IL-15 preferentially enhances the activation and effector function
      of human effector-memory CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-) CD4(+) and
      CD8(+) T cells in both healthy and HIV-infected individuals. We find that IL-15
      increases 2- to 5-fold both the activation and secretion of the effector
      cytokines IFN-gamma and tumor necrosis factor (TNF)-alpha by anti-CD3-stimulated
      purified CD4(+) and CD8(+) T cells and peripheral blood mononuclear cells from
      healthy and HIV-infected individuals. Furthermore, IL-15 potently inhibits
      CD95/Fas-induced apoptosis of the effector-memory CD4(+) and CD8(+) T cells from
      HIV-infected individuals. These findings suggest that in addition to being a
      growth and survival factor for memory CD8(+) T cells, IL-15 is also a potent
      activator of human effector-memory CD8(+) T cells both in healthy and in HIV
      infected individuals.

PMID- 12502726
TI  - Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova
      immunization.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple
      sclerosis (MS) characterized by chronic inflammatory demyelination of the central
      nervous system (CNS). The pathology of EAE involves autoimmune CD4(+) T(h)1
      cells. There is a striking inverse correlation between the occurrence of
      parasitic and autoimmune diseases. We demonstrate that in mice with Schistosoma
      mansoni ova immunization, the severity of EAE is reduced as measured by decreased
      clinical scores and CNS cellular infiltrates. Disease suppression is associated
      with immune deviation in the periphery and the CNS, demonstrated by decreased IFN
      gamma and increased IL-4, transforming growth factor-beta and IL-10 levels in the
      periphery, and increased frequency of IL-4 producing neuroantigen-specific T
      cells in the brain. S. mansoni helminth ova treatment influenced the course of
      EAE in wild-type mice, but not in STAT6-deficient animals. This indicates that
      STAT6 plays a critical role in regulating the ameliorating effect of S. mansoni
      ova treatment on the autoimmune response, and provides the direct link between
      helminth treatment, T(h)2 environment and improved EAE. As some intestinal
      helminthic infections induce minimal pathology, they might offer a safe and
      inexpensive therapy to prevent and/or ameliorate MS.

PMID- 12502727
TI  - Potential preventive effects of follistatin-related protein/TSC-36 on joint
      destruction and antagonistic modulation of its autoantibodies in rheumatoid
      arthritis.
AB  - We previously reported that follistatin-related protein (FRP)/TSC-36 was one of
      the target antigens of autoantibodies in rheumatoid arthritis (RA) and that the
      appearance of serum autoantibodies to FRP correlated to disease activity in RA.
      However, the significance of FRP in autoimmunity remained to be explained due to
      the unknown function of FRP. Here, we disclose in part the function of FRP.
      Transforming growth factor (TGF)-beta augmented FRP gene expression in synovial
      cells. FRP reduced synovial production of matrix metalloproteinase (MMP)-1, MMP-3
      and prostaglandin E(2), potent agonists of joint destruction in RA. In contrast,
      autoantibodies to FRP from patients with RA increased their production by
      blocking FRP activity, probably in the autocrine system. Moreover, FRP down
      regulated synovial expression of FOS (c-fos), which seemed responsible for the
      reduction in MMP-1 and MMP-3 caused by FRP. Therefore, FRP and its autoantibody
      can be regarded as defensive and offensive factors respectively in rheumatoid
      arthropathy. The major epitope of autoantibodies to FRP was mapped to the
      sequence LKFVEQNE (residues 169-176) and homologous sequences were found in
      proteins from Escherichia coli, Epstein-Barr virus, etc. FRP and its autoantibody
      may provide some clues to elucidate the process of disease development and a new
      approach to the design of therapeutics in RA.

PMID- 12502728
TI  - Superantigenic activity is responsible for induction of coronary arteritis in
      mice: an animal model of Kawasaki disease.
AB  - Kawasaki disease (KD) is a multisystem vasculitis and the leading cause of
      acquired heart disease in children of the developed world. Lactobacillus casei
      cell wall extract-induced coronary arteritis in mice mirrors KD in children.
      Here, we report that responses to L. casei cell wall extract possess all the
      hallmarks of a superantigen-mediated response: marked proliferation of naive T
      cells, non-classical major histocompatibility restriction with a hierarchy in the
      efficiency of different class II molecules to present this superantigen, a
      requirement for antigen presentation, but not processing, and stimulation of T
      cells in a non-clonal, TCR V(beta) chain-dependent fashion. This superantigenic
      activity directly correlates with the ability to induce coronary arteritis in
      mice. Taken together, our findings demonstrate that superantigenic activity in L.
      casei cell wall extract is responsible for induction of coronary artery disease.

PMID- 12502729
TI  - Improvement of long-lasting response and antibody affinity by the complexation of
      antigen with complement C3b.
AB  - Complement protein C3 plays a major role in cell regulation and immune response.
      This last point is mainly due to C3's capacity to act as a bifunctional link
      between antigen and immunocompetent cells. In a previous work, we have reported
      the adjuvant effect produced by linking C3 fragments to antigen. In this paper,
      we characterize the long-term secondary antibody response induced by C3b-antigen
      complexes. Mice were immunized using either a protein (hen egg lysozyme) or an
      ovalbumin-derived peptide as antigen. We compared the secondary response elicited
      by these antigens covalently linked to C3b or emulsified in complete Freund's
      adjuvant (CFA). Our results provide evidence that C3b linkage induces better long
      term adjuvant effect than CFA, resulting in the production of a higher specific
      IgG titer with a better affinity.

PMID- 12502730
TI  - Role of the CD5 molecule on TCR gammadelta T cell-mediated immune functions:
      development of germinal centers and chronic intestinal inflammation.
AB  - Although CD4(+) T cells form a major subset of TCRalphabeta T cells, only a small
      number of TCRgammadelta T cells express CD4. Factors contributing to the down
      regulation of CD4(+) TCRgammadelta T cells have not been identified. The CD5
      molecule is expressed on most TCRgammadelta T cells in the spleen, whereas only a
      few intestinal intraepithelial TCRgammadelta T cells express this molecule in
      wild-type mice and TCRbeta mutant (beta(-/-)) mice. Unexpectedly, in the present
      studies, the lack of CD5 led to a remarkable increase of a CD4(+) TCRgammadelta T
      cell subset in CD5(-/-)beta(-/-) mice. The CD4(+) TCRgammadelta T cells were also
      detectable in MHC II(-/-)CD5(-/-)beta(-/-) triple-mutant mice. This CD4(+)
      TCRgammadelta T cell subset provided help in Mycobacterium-induced germinal
      center (GC) formation and showed a T(h)-like cytokine profile. In contrast,
      CD5(+) TCRgammadelta T cells suppressed the CD4(+) TCRgammadelta T cell-mediated
      GC formation, presumably by eliminating this CD4(+) subset. Unlike
      intraepithelial gammadelta T cells, >30% of TCRgammadelta T cells in the colonic
      lamina propria (LP) expressed CD5. The lack of CD5 also led to increased numbers
      of CD4(+) TCRgammadelta T cells in the colonic LP and increased susceptibility to
      development of chronic colitis in beta(-/-) mice. Cell transfer studies suggest
      that CD5(+) TCRgammadelta T cells are capable of selectively eliminating CD4(+)
      TCRgammadelta T cells in the intestine. The CD4(+) TCRgammadelta T cells possess
      immune functions similar to CD4(+) TCRalphabeta T cells.

PMID- 12502731
TI  - Expression of H-ficolin/Hakata antigen, mannose-binding lectin-associated serine
      protease (MASP)-1 and MASP-3 by human glioma cell line T98G.
AB  - Mannose-binding lectin (MBL) is a C-type lectin involved in the first line of
      host defense and it requires MBL-associated serine proteases (MASP) for
      activation of the lectin complement pathway (LCP). Recently we reported that
      human ficolins, L-ficolin/P35 and H-ficolin/Hakata antigen, as well as MBL
      activate the LCP in association with MASP. We investigated in vitro expression of
      complements of the lectin complement pathway in several cell lines. Out of 17
      cell lines tested using RT-PCR, a human glioma cell line, T98G, expressed high
      levels of H-ficolin/Hakata antigen, MASP1 and MASP3 mRNAs. Similar results were
      obtained in four other glioma lines. In addition, mRNAs for C1r, C1s, C2, C3, C4,
      C5 and C6 were also detected in T98G cells, but very low amount of mRNAs for C1q
      and MBL. MBL mRNA was seen in two of the other glioma cell lines. An ELISA of
      culture supernatants showed that T98G cells secreted a considerable amount of
      MASP-1 and MASP-3 proteins. SDS-PAGE and immunoblotting analyses showed the
      secreted H-ficolin/Hakata antigen, MASP-1 and MASP-3 to be 34, 81 and 105 kDa in
      size respectively, similar to their serum counterparts. Since the glioma cells
      used are derived from astrocytes, this suggests that human astrocytes may be a
      source of some components of the LCP in the brain.

PMID- 12502732
TI  - Prolonged presence of effector-memory CD8 T cells in the central nervous system
      after dengue virus encephalitis.
AB  - Dengue virus infection in the central nervous system (CNS) of immunized mice
      results in a strong influx of CD8 T cells into the brain. Whereas the kinetics of
      the splenic antiviral response are conventional, i.e. expansion followed by a
      rapid drop in the frequency of specific CD8 T cells, dengue virus-specific CD8 T
      cells are retained in the CNS at a high frequency. These CD8 T cells display a
      partially activated phenotype (CD69(high), Ly-6A/E(high), CD62L(low)),
      characteristic for effector-memory T cells. CD43 expression, visualized by
      staining with the 1B11 mAb, decreased in time, suggesting that these persisting
      CD8 T cells differentiated into memory cells. These data add to the growing
      evidence implicating the CNS as a non-lymphoid tissue capable of supporting
      prolonged T cell survival/maintenance.

PMID- 12502733
TI  - CD4 T cell priming in dendritic cell-deficient mice.
AB  - Bone marrow (BM) chimeras (BMC) generated from mice carrying a null (-/-)
      mutation in the relB gene of the NF-kappaB family represent an ideal model for in
      vivo studies on the role of dendritic cells (DC) in the adaptive immune response.
      The spleen and lymph nodes (LN) of relB(-/-) BMC contain a small number of
      residual DC, mainly CD8alpha(+), that fail to up-regulate MHC class II and co
      stimulatory molecules after stimulation in vitro. Moreover, residual spleen DC of
      relB(-/-) BMC have a 4-fold decrease in the ability to uptake and process soluble
      model antigen, ovalbumin (OVA), and failed to prime CD4 and CD8 T cells in vitro
      and in vivo. In addition, they also failed to present OVA peptide to OT-II
      transgenic T lymphocytes at a normal 1:10 (stimulator:responder) cell ratio. In
      spite of these multiple DC defects, relB(-/-) BMC immunized with plasmid DNA
      targeted to the spleen as the site of immune induction develop a specific CD4(+)
      T cell response comparable to that of relB competent mice. These data demonstrate
      that CD4( +) T cells can be primed in the absence of functional DC and suggest
      that relB may gauge the T cell response in vivo.

PMID- 12502734
TI  - Steroid signaling in plants and insects--common themes, different pathways.

PMID- 12502735
TI  - Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1
      ring complex.
AB  - The acetylation of histone tails is a primary determinant of gene activity.
      Histone deacetylase 3 (HDAC3) requires the nuclear receptor corepressor SMRT for
      HDAC enzyme activity. Here we report that HDAC3 interacts with SMRT only after
      priming by cellular chaperones including the TCP-1 ring complex (TRiC), which is
      required for proper folding of HDAC3 in an ATP-dependent process. SMRT displaces
      TRiC from HDAC3, yielding an active HDAC enzyme. The SMRT-HDAC3 repression
      complex thus joins the VHL-elongin BC tumor suppression complex and the cyclin E
      Cdk2 cell cycle regulation complex as critical cellular machines requiring TRiC
      for proper assembly and function. The strict control of HDAC3 activity
      underscores the cellular imperative that histone deacetylation occur only in
      targeted regions of the genome.

PMID- 12502736
TI  - LIN-39/Hox triggers cell division and represses EFF-1/fusogen-dependent vulval
      cell fusion.
AB  - General mechanisms by which Hox genes establish cell fates are known. However, a
      few Hox effectors mediating cell behaviors have been identified. Here we found
      the first effector of LIN-39/HoxD4/Dfd in Caenorhabditis elegans. In specific
      vulval precursor cells (VPCs), LIN-39 represses early and late expression of EFF
      1, a membrane protein essential for cell fusion. Repression of eff-1 is also
      achieved by the activity of CEH-20/Exd/Pbx, a known cofactor of Hox proteins.
      Unfused VPCs in lin-39(-);eff-1(-) double mutants fail to divide but migrate,
      executing vulval fates. Thus, lin-39 is essential for inhibition of EFF-1
      dependent cell fusion and stimulation of cell proliferation during vulva
      formation. Supplemental material is available at http://www.genesdev.org.

PMID- 12502737
TI  - Nob1p is required for biogenesis of the 26S proteasome and degraded upon its
      maturation in Saccharomyces cerevisiae.
AB  - Nob1p is a nuclear protein that forms a complex with the 19S regulatory particle
      of the 26S proteasome and with uncharacterized nuclear protein Pno1p.
      Overexpression of NOB1 overrode the defects in maturation of the 20S proteasome
      of ump1Delta cells, and temperature-sensitive nob1 and pno1 mutants exhibited
      defects in the processing of the beta subunits and in the assembly of the 20S and
      the 26S proteasomes. A defect in either NOB1 or PNO1 caused accumulation of newly
      formed Pre6p in the cytoplasm, whereas Pre6p of the ump1Delta strain accumulated
      in the nucleus irrespective of the temperature. Here we present a model proposing
      that (1) Nob1p serves as a chaperone to join the 20S proteasome with the 19S
      regulatory particle in the nucleus and facilitates the maturation of the 20S
      proteasome and degradation of Ump1p, and (2) Nob1p is then internalized into the
      26S proteasome and degraded to complete 26S proteasome biogenesis.

PMID- 12502738
TI  - Receptor-mediated endoproteolytic activation of two transcription factors in
      yeast.
AB  - Yeast possess a plasma membrane sensor of external amino acids that functions as
      a ligand-activated receptor. This multimeric sensor, dubbed the SPS sensor,
      initiates signals that regulate the expression of genes required for proper amino
      acid uptake. Stp1p and Stp2p are transcription factors that bind to specific
      sequences within the promoters of SPS-sensor-regulated genes. These factors
      exhibit redundant and overlapping abilities to activate transcription. We have
      found that Stp1p and Stp2p are synthesized as latent cytoplasmic precursors. In
      response to extracellular amino acids, the SPS sensor induces the rapid
      endoproteolytic processing of Stp1p and Stp2p. The processing of Stp1p/Stp2p
      occurs independently of proteasome function and without the apparent involvement
      of additional components. The shorter forms of these transcription factors,
      lacking N-terminal inhibitory domains, are targeted to the nucleus, where they
      transactivate SPS-sensor target genes. These results define a completely unique
      and streamline metabolic control pathway that directly routes environmental
      signals initiated at the plasma membrane to transcriptional activation in the
      nucleus of yeast.

PMID- 12502739
TI  - FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth
      organogenesis in Lef1(-/-) mice.
AB  - Lymphoid enhancer factor (LEF1), a nuclear mediator of Wnt signaling, is required
      for the formation of organs that depend on inductive interactions between
      epithelial and mesenchymal tissues. In previous tissue recombination experiments
      with normal and Lef1(-/-) tooth germs, we found that the effect of LEF1
      expression in the epithelium is tissue nonautonomous and transferred to the
      subjacent mesenchyme. Here we examine the molecular basis for LEF1 function and
      find that the epithelium of the developmentally arrested Lef1(-/-) tooth
      rudiments fails to express Fgf4, Shh, and Bmp4, but not Wnt10a. We identify the
      Fgf4 gene as a direct transcriptional target for LEF1 and show that beads soaked
      with recombinant FGF4 protein can fully overcome the developmental arrest of
      Lef1(-/-) tooth germs. In addition, we find that FGF4 beads induce rapidly the
      expression of Fgf3 in dental mesenchyme and that both epithelial and mesenchymal
      FGF proteins induce the delayed expression of Shh in the epithelium. Taken
      together, these data indicate that a single target of LEF1 can account for the
      function of LEF1 in tooth development and for a relay of a Wnt signal reception
      to a cascade of FGF signaling activities, allowing for a sequential and
      reciprocal communication between epithelium and mesenchyme.

PMID- 12502740
TI  - Biological functions of the ISWI chromatin remodeling complex NURF.
AB  - The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein
      complexes that catalyze ATP-dependent nucleosome sliding and facilitate
      transcription of chromatin in vitro. To establish the physiological requirements
      of NURF, and to distinguish NURF genetically from other ISWI-containing
      complexes, we isolated mutations in the gene encoding the large NURF subunit,
      nurf301. We confirm that NURF is required for transcription activation in vivo.
      In animals lacking NURF301, heat-shock transcription factor binding to and
      transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show
      that NURF is required for homeotic gene expression. Consistent with this, nurf301
      mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator
      of the Bithorax-Complex previously localized to the same genetic interval.
      Finally, mutants in NURF subunits exhibit neoplastic transformation of larval
      blood cells that causes melanotic tumors to form.

PMID- 12502741
TI  - Structural basis for the recognition of the E2F transactivation domain by the
      retinoblastoma tumor suppressor.
AB  - Repression of E2F transcription activity by the retinoblastoma (Rb) tumor
      suppressor through its interaction with the transactivation domain of the E2F
      transcription factor is one of the central features of G1/S arrest in the
      mammalian cell cycle. Deregulation of the Rb-E2F interaction results in
      hyperproliferation, lack of differentiation, and apoptosis, and can lead to
      cancer. The 2.2-A crystal structure of the Rb pocket complexed with an 18-residue
      transactivation-domain peptide of E2F-2 reveals that the boomerang-shaped peptide
      binds to the highly conserved interface between the A-box and the B-box of the Rb
      pocket in a bipartite manner. The N-terminal segment of the E2F-2 peptide in an
      extended beta-strand-like structure interacts with helices from the conserved
      groove at the A-B interface, whereas the C-terminal segment, which contains one
      3(10) helix, binds to a groove mainly formed by A-box helices. The flexibility in
      the middle of the E2F-2 peptide is essential for the tight association of E2F to
      the Rb pocket. The binding of Rb to the E2F-2 peptide conceals several conserved
      residues that are crucial for transcription activation of E2F. We provide the
      structural basis for the Rb-mediated repression of E2F transcription activity
      without the requirement of histone-modifying enzymes.

PMID- 12502742
TI  - Lipoatrophic diabetes in Irs1(-/-)/Irs3(-/-) double knockout mice.
AB  - Based on the phenotypes of knockout mice and cell lines, as well as pathway
      specific analysis, the insulin receptor substrates IRS-1, IRS-2, IRS-3, and IRS-4
      have been shown to play unique roles in insulin signal transduction. To
      investigate possible functional complementarity within the IRS family, we
      generated mice with double knockout of the genes for IRS-1/IRS-3 and IRS-1/IRS-4.
      Mice with a combined deficiency of IRS-1 and IRS-4 showed no differences from
      Irs1(-/-) mice with respect to growth and glucose homeostasis. In contrast, mice
      with a combined deficiency of IRS-1 and IRS-3 developed early-onset severe
      lipoatrophy associated with marked hyperglycemia, hyperinsulinemia, and insulin
      resistance. However, in contrast to other models of lipoatrophic diabetes, there
      was no accumulation of fat in liver or muscle. Furthermore, plasma leptin levels
      were markedly decreased, and adenovirus-mediated expression of leptin in liver
      reversed the hyperglycemia and hyperinsulinemia. The results indicate that IRS-1
      and IRS-3 play important complementary roles in adipogenesis and establish the
      Irs1(-/-)/Irs3(-/-) double knockout mouse as a novel model of lipoatrophic
      diabetes.

PMID- 12502743
TI  - The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet
      enveloping and secretion: gene sharing in the lactating mammary gland.
AB  - Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism
      occurring in most cell types. However, this housekeeping gene is expressed at
      very high levels in a number of mammalian tissues including the lactating mammary
      epithelium, suggesting additional roles for XOR in these tissues. Mice with
      targeted disruption of XOR were generated to assess these potential additional
      roles. XOR-/- mice are runted and do not live beyond 6 wk of age. Strikingly,
      however, XOR+/- females, although of healthy appearance and normal fertility, are
      unable to maintain lactation and their pups die of starvation 2 wk postpartum.
      Histological and whole-mount analyses showed that in XOR+/- females the mammary
      epithelium collapses, resulting in premature involution of the mammary gland.
      Electron microscopy showed that XOR is specifically required for enveloping milk
      fat droplets with the apical plasma membrane prior to secretion from the
      lactating mammary gland. We present evidence that XOR may have primarily a
      structural role, as a membrane-associated protein, in milk fat droplet secretion
      and thus XOR provides another example of "gene sharing". About 5% of women
      experience primary lactation insufficiency. The above observations suggest that
      human females suffering from xanthinuria, a deficiency in XOR, are potential
      candidates for lactation problems.

PMID- 12502744
TI  - ORC and the intra-S-phase checkpoint: a threshold regulates Rad53p activation in
      S phase.
AB  - The intra-S-phase checkpoint in yeast responds to stalled replication forks by
      activating the ATM-like kinase Mec1 and the CHK2-related kinase Rad53, which in
      turn inhibit spindle elongation and late origin firing and lead to a
      stabilization of DNA polymerases at arrested forks. A mutation that destabilizes
      the second subunit of the Origin Recognition Complex, orc2-1, reduces the number
      of functional replication forks by 30% and severely compromises the activation of
      Rad53 by replication stress or DNA damage in S phase. We show that the
      restoration of the checkpoint response correlates in a dose-dependent manner with
      the restoration of pre-replication complex formation in G1. Other forms of DNA
      damage can compensate for the reduced level of fork-dependent signal in the orc2
      1 mutant, yet even in wild-type cells, the amount of damage required for Rad53
      activation is higher in S phase than in G2. Our data suggest the existence of an
      S-phase-specific threshold that may be necessary to allow cells to tolerate
      damage-like DNA structures present at normal replication forks.

PMID- 12502745
TI  - A cytoskeleton-like role for the bacterial cell wall during engulfment of the
      Bacillus subtilis forespore.
AB  - A hallmark of bacterial endospore formation is engulfment, during which the
      membrane of one cell (the mother cell) migrates around the future spore,
      enclosing it in the mother cell cytoplasm. Bacteria lack proteins required for
      eukaryotic phagocytosis, and previously proteins required for membrane migration
      remained unidentified. Here we provide cell biological and genetic evidence that
      three membrane proteins synthesized in the mother cell are required for membrane
      migration as well as for earlier steps in engulfment. Biochemical studies
      demonstrate that one of these proteins, SpoIID, is a cell wall hydrolase,
      suggesting that membrane migration in bacteria can be driven by membrane-anchored
      cell wall hydrolases. We propose that the bacterial cell wall plays a role
      analogous to that of the actin and tubulin network of eukaryotic cells, providing
      a scaffold along which proteins can move.

PMID- 12502746
TI  - The NC2 alpha and beta subunits play different roles in vivo.
AB  - NC2 is a heterodimeric regulator of transcription that plays both positive and
      negative roles in vivo. Here we show that the alpha and beta subunits of yeast
      NC2 are not always associated in a tight complex. Rather, their association is
      regulated, in particular by glucose depletion. Indeed, stable NC2 alpha/beta
      complexes can only be purified from cells after the diauxic shift when glucose
      has been depleted from the growth medium. In vivo, the presence of NC2 alpha, but
      not NC2 beta, at promoters generally correlates with the presence of TBP and
      transcriptional activity. In contrast, increased presence of NC2 beta relative to
      TBP correlates with transcriptional repression. NC2 is regulated by
      phosphorylation. We found that mutation of genes encoding casein kinase II (CKII)
      subunits as well as potential CKII phosphorylation sites in NC2 alpha and beta
      affected gene repression. Interestingly, NC2-dependent repression in the
      phosphorylation site mutants was only perturbed in high glucose when NC2 beta and
      NC2 alpha are not associated, but not after the diauxic shift when NC2 alpha and
      beta form stable complexes. Thus, the separation of NC2 alpha and beta function
      indicated by these mutants also supports the existence of multiple NC2 complexes
      with different functions in transcription.

PMID- 12502747
TI  - Development of mice expressing a single D-type cyclin.
AB  - D-cyclins (cyclins D1, D2, and D3) are components of the core cell cycle
      machinery. To directly test the ability of each D-cyclin to drive development of
      various lineages, we generated mice expressing only cyclin D1, or only cyclin D2,
      or only cyclin D3. We found that these "single-cyclin" embryos develop normally
      until late gestation. Our analyses revealed that in single-cyclin embryos, the
      tissue-specific expression pattern of D-cyclins was lost. Instead, mutant embryos
      ubiquitously expressed the remaining D-cyclin. These findings suggest that the
      functions of the three D-cyclins are largely exchangeable at this stage. Later in
      life, single-cyclin mice displayed focused abnormalities, resulting in premature
      mortality. "Cyclin D1-only" mice developed severe megaloblastic anemia, "cyclin
      D2-only" mice presented neurological abnormalities, and "cyclin D3-only" mice
      lacked normal cerebella. Analyses of the affected tissues revealed that these
      compartments failed to sufficiently up-regulate the remaining, intact D-cyclin.
      In particular, we found that in cerebellar granule neuron precursors, the N-myc
      transcription factor communicates with the cell cycle machinery via cyclins D1
      and D2, but not D3, explaining the inability of D3-only mice to up-regulate
      cyclin D3 in this compartment. Hence, the requirement for a particular cyclin in
      a given tissue is likely caused by specific transcription factors, rather than by
      unique properties of cyclins.

PMID- 12502748
TI  - The antigen-antibody reaction in immunohistochemistry.
AB  - The problems of major concern in immunohistochemical practice are discussed in
      the following order: (a) the mechanism of the Ag-Ab reaction in fixed tissue as
      opposed to the in vitro reaction; (b) the chemistry of fixation and its influence
      on the final result of the immunohistochemical reaction; (c) the various
      procedures used for antigen retrieval in formaldehyde-fixed tissue; and (d) the
      consideration of the possible mechanism underlying heat-induced antigen
      retrieval. Suggestions for further work to attempt a clarification of the
      mechanism involved in the Ag-Ab reaction in immunohistochemistry resorting to
      existing histochemical methods for the demonstration of protein side groups are
      presented, together with some examples already published.

PMID- 12502749
TI  - Simultaneous detection of EGFP and cell surface markers by fluorescence
      microscopy in lymphoid tissues.
AB  - Enhanced GFP (EGFP) is a powerful tool for the visualization of tagged proteins
      and transfected cells and is easily detected by fluorescence microscopy or flow
      cytometry in living cells. However, soluble EGFP molecules can be lost if cell
      integrity is disrupted by freezing, sectioning, or permeablization. Furthermore,
      the fluorescence of EGFP is dependent on its conformation. Therefore, fixation
      protocols that immobilize EGFP may also destroy its usefulness as a fluorescent
      reporter. Here we determined which methods of preparing murine lymphoid tissues
      immobilized soluble EGFP protein and retained its fluorescence while
      simultaneously maintaining the antigenicity of various immunologically important
      molecules and best preserving the overall morphology of the tissues. We found
      that EGFP could not be visualized in frozen sections of spleen that had not been
      fixed before freezing. However, robust EGFP fluorescence could be observed in
      frozen sections of tissues fixed under various conditions. Fixation was important
      to immobilize EGFP rather than to maintain conformation, because only minimal
      EGFP could be detected by immunofluorescence in unfixed frozen sections. Although
      it had little effect on EGFP fluorescence, the inclusion of sucrose during
      fixation better preserved the morphology of fixed tissues. These methods also
      preserved the antigenicity of a wide variety of molecules used to identify cell
      types in lymphoid tissues.

PMID- 12502750
TI  - Detection of PrP(sc) in samples presenting a very advanced degree of autolysis
      (BSE liquid state) by immunocytochemistry.
AB  - Although detection of the abnormal isoform of prion protein (PrP(sc)), the
      specific feature of transmissable spongiform encephalopathies (TSEs), has been
      previously demonstrated on formalin-fixed autolytic tissue, no samples with
      autolysis as severe as tested here (i.e., liquid state) have previously been
      tested. It is inevitable that a small but significant proportion of brains,
      especially in summer due to delays in postmortem examination, undergo an
      extremely severe autolysis that makes samples unsuitable for diagnosis by
      conventional techniques. In this study, 25 bovine samples were diagnosed by
      applying immunocytochemistry on the corresponding liquid fraction. Four
      additional portions of brainstem (positive and negative sheep and cattle) were
      subjected to one of the autolysis regimens at 56C or environmental conditions for
      up to 80 days and were analyzed with the same methodology. No abnormal protein
      could be detected in any of the control animals. PrP(sc) accumulation was
      observed by immunocytochemistry in all cases that were positive by either
      immunohistochemistry on the corresponding filtrates or by Prionics Western
      blotting, showing an excellent agreement between the methodology assessed and
      these routine techniques. The results of this study demonstrate
      immunocytochemistry as a useful tool for diagnosis in liquid-state samples,
      solving a most relevant problem in BSE and scrapie epidemiology.

PMID- 12502751
TI  - Simultaneous imaging and functional assessment of cytoskeletal protein
      connections in passively loaded single muscle cells.
AB  - We describe a novel system that permits simultaneous confocal imaging of protein
      interactions and measurement of cell mechanical properties during passive
      loading. A mechanical apparatus was designed to replace the stage of a confocal
      microscope, enabling cell manipulation, force transduction, and imaging. In
      addition, image processing algorithms were developed to quantify the degree of
      connectivity between subcellular structures. Using this system, we examined the
      interactions among three cellular structures thought to be linked by the muscle's
      intermediate filament system: Z-disks, nuclei, and the costamere protein
      complexes located at the muscle cell surface. Fast Fourier transforms (FFTs) and
      autocorrelations (ACs) were implemented to quantify image periodicity and
      relative phase shifts among structures. We demonstrated in sample wild-type
      muscle cells that there was significant connectivity among Z-disks in the same
      fiber at various sarcomere lengths, as well as between Z-disks and the costamere
      complexes. This approach can be applied to any cell system in which structural
      periodicity and mechanical connectivity are of interest.

PMID- 12502752
TI  - A new method to enhance contrast of ultrathin cryosections for immunoelectron
      microscopy.
AB  - Adequate contrast of ultrathin cryosections is crucial for evaluating
      morphological detail to assess immunocytochemical localization at the electron
      microscopic level. We have developed a positive staining method for achieving
      contrast in ultrathin cryosections, from tissue fixed only in paraformaldehyde,
      that provides excellent contrast at the electron microscopic level.

PMID- 12502753
TI  - Expression of Arnt and Arnt2 mRNA in developing murine tissues.
AB  - The basic helix-loop-helix (bHLH-PAS) proteins aryl hydrocarbon receptor nuclear
      translocator (Arnt) and Arnt2 are transcriptional regulators that function as
      dimerizing partners for several bHLH-PAS proteins and also some nonrelated
      partners. They are involved in various biological functions, including regulation
      of developmental genes. In earlier studies, the developmental expression of Arnt
      was reported to be almost ubiquitous, whereas Arnt2 expression has been shown to
      be more limited, comprising neuronal tissues as the main site of expression. Here
      we provide a detailed description of the expression of Arnt and Arnt2 mRNA in
      mouse tissues during embryonic and early postnatal development. Arnt and also
      Arnt2 transcripts, in contrast to earlier reports, are shown to be expressed more
      widely during development yet show a temporally and spatially specific pattern.

PMID- 12502754
TI  - Localization of messenger ribonucleic acids for somatostatin receptor subtypes
      (sstr1-5) in the rat adrenal gland.
AB  - Somatostatin (somatotropin-release inhibitory factor, SRIF) exerts multiple
      inhibitory actions throughout the central nervous system and the periphery by
      binding to specific membrane-bound SRIF receptors (sstrs) of which five subtypes
      (sstr1-5) have now been identified. Individual sstr subtypes have been suggested
      to mediate selective biological actions of SRIF. Although the adrenal gland is a
      known target of SRIF action, the sstr subtypes involved in its actions are
      unclear. This study examined the expression of sstr1-5 in rat adrenal gland by RT
      PCR analysis and in situ hybridization (ISH) histochemistry. Using RT-PCR
      expression combined with Southern blotting, sstr1, -2, -4, and -5 mRNAs were
      shown in the adrenal gland. ISH histochemistry revealed strong expression of
      sstr2 mRNA alone localized to the zona glomerulosa of the adrenal cortex and
      moderate labeling in scattered cells of the adrenal medulla, indicating a
      possible role for sstr2 in mediating SRIF physiology in this tissue by altering
      adrenal aldosterone and catecholamine secretion. These data also point to
      potential roles for sstr subtypes sstr1, -4, and -5 in the adrenal gland.

PMID- 12502755
TI  - Quantitative immunogold labeling of bone sialoprotein and osteopontin in
      methylmethacrylate-embedded rat bone.
AB  - Methylmethacrylate (MMA) embedding of undecalcified bone is routinely employed
      for histomorphometric analyses. Although MMA-embedded bone has been used for
      immunolabeling at the light microscopic level after removal of the resin, there
      are no such reports for electron microscopy. The aim of the present study was to
      determine whether MMA embedding can be used for ultrastructural immunolabeling
      and how it compares to LR White (LRW), an acrylic resin frequently used for
      immunocytochemistry of bone. Rat tibiae were fixed by vascular perfusion with
      aldehyde and embedded either in MMA or LRW resin. Thin sections were processed
      for postembedding protein A-gold immunolabeling with antibodies to rat bone
      sialoprotein (BSP) and osteopontin (OPN). The density of gold particles over bone
      was quantified. The density and distribution of immunolabeling for BSP and OPN
      respectively, were comparable between MMA and LRW. These results indicate that
      MMA performs as well as LRW for the ultrastructural immunolabeling of
      noncollagenous bone matrix proteins.

PMID- 12502756
TI  - Electron microscopic immunogold localization of salivary mucins MG1 and MG2 in
      human submandibular and sublingual glands.
AB  - The human salivary mucins MG1 and MG2 are well characterized biochemically and
      functionally. However, there is disagreement regarding their cellular and
      glandular sources. The aim of this study was to define the localization and
      distribution of these two mucins in human salivary glands using a postembedding
      immunogold labeling method. Normal salivary glands obtained at surgery were fixed
      in 3% paraformaldehyde-0.1% glutaraldehyde and embedded in Lowicryl K4M or LR
      Gold resin. Thin sections were labeled with rabbit antibodies to MG1 or to an N
      terminal synthetic peptide of MG2, followed by gold-labeled goat anti-rabbit IgG.
      The granules of all mucous cells of the submandibular and sublingual glands were
      intensely reactive with anti-MG1. No reaction was detected in serous cells. With
      anti-MG2, the granules of both mucous and serous cells showed reactivity. The
      labeling was variable in both cell types, with mucous cells exhibiting a stronger
      reaction in some glands and serous cells in others. In serous granules, the
      electron-lucent regions were more reactive than the dense cores. Intercalated
      duct cells near the acini displayed both MG1 and MG2 reactivity in their apical
      granules. In addition, the basal and lateral membranes of intercalated duct cells
      were labeled with anti-MG2. These results confirm those of earlier studies on MG1
      localization in mucous cells and suggest that MG2 is produced by both mucous and
      serous cells. They also indicate differences in protein expression patterns among
      salivary serous cells.

PMID- 12502757
TI  - Expression of endothelial nitric oxide synthase in ciliated epithelia of rats.
AB  - Endothelial nitric oxide synthase (eNOS), originally found in the endothelium of
      vascular tissue, also exists in other cell types, including ciliated epithelia of
      airways. The eNOS is ultrastructurally localized to the basal body of the
      microtubules of the cilia, and nitric oxide (NO) stimulates ciliary beat
      frequency (CBF). We examined whether the expression of eNOS is present in
      ciliated cells of other organs. Western blotting analysis revealed that eNOS was
      expressed in the rat cerebrum, lung, trachea, testis, and oviduct.
      Immunohistochemical staining showed that eNOS was localized in the ciliated
      epithelia of airways, oviduct, testis, and ependymal cells of brain in addition
      to the endothelium and smooth muscle of the vasculature. To confirm the
      activation of eNOS in the ciliated epithelia, we examined the effect of L
      arginine (L-Arg), the substrate of NOS, on the production of nitrite and nitrate
      (NOx) in the cultured explants of rat trachea. L-Arg (100 microM) increased NOx
      levels significantly (p<0.05). In explants exposed to inhibitors of NOS, the
      effect of l-Arg on the production of NOx was blocked. These findings suggest that
      epithelial NO plays an important role in signal transduction associated with
      ciliary functions.

PMID- 12502758
TI  - Cellular characterization of epidermal growth factor-expanded free-floating
      neurospheres.
AB  - Neural stem cells proliferate in liquid culture as cell clusters (neurospheres).
      This study was undertaken to characterize the epidermal growth factor (EGF)
      expanded free-floating neurospheres derived from rat fetal striatum. We examined
      the ultrastructural and antigenic characteristics of these spheres. They
      consisted of two cell types, electron-dense and electron-lucent cells. Lucent
      cells were immunopositive to actin, vimentin, and nestin, whereas dense cells
      were immunopositive to actin, weakly positive to vimentin, and nestin-negative.
      Neurospheres contained healthy, apoptotic, and necrotic cells. Healthy cells were
      attached to each other by adherens junctions. They showed many pseudopodia and
      occasionally a single cilium. Sphere cells showed phagocytic capability because
      healthy cells phagocytosed the cell debris derived from dead cells in a
      particular process that involves the engulfment of dying cells by cell processes
      from healthy cells. Sphere cells showed a cytoplasmic and a nuclear pool of
      fibroblast growth factor (FGF) receptors. They expressed E- and N-cadherin, alpha
      and beta-catenin, EGF receptor, and a specific subset of FGF receptors. Because
      sphere cells expressed this factor in the absence of exogenous FGF-2, we propose
      that they are able to synthesize FGF-2.

PMID- 12502759
TI  - Post-translational regulation of glucose-6-phosphate dehydrogenase activity in
      (pre)neoplastic lesions in rat liver.
AB  - Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is the key regulatory
      enzyme of the pentose phosphate pathway and produces NADPH and riboses. In this
      study, the kinetic properties of G6PD activity were determined in situ in
      chemically induced hepatocellular carcinomas, and extralesional and control
      parenchyma in rat livers and were directly compared with those of the second
      NADPH-producing enzyme of the pentose phosphate pathway, phosphogluconate
      dehydrogenase (PGD). Distribution patterns of G6PD activity, protein, and mRNA
      levels were also compared to establish the regulation mechanisms of G6PD
      activity. In (pre)neoplastic lesions, the V(max) of G6PD was 150-fold higher and
      the K(m) for G6P was 10-fold higher than in control liver parenchyma, whereas in
      extralesional parenchyma, the V(max) was similar to that in normal parenchyma but
      the K(m) was fivefold lower. This means that virtual fluxes at physiological
      substrate concentrations are 20-fold higher in lesions and twofold higher in
      extralesional parenchyma than in normal parenchyma. The V(max) of PGD was
      fivefold higher in lesions than in normal and extralesional liver parenchyma,
      whereas the K(m) was not affected. Amounts of G6PD protein and mRNA were similar
      in lesions and in extralesional liver parenchyma. These results demonstrate that
      G6PD is strongly activated post-translationally in (pre)neoplastic lesions to
      produce NADPH.

PMID- 12502760
TI  - Myosin heavy chain composition in human masticatory muscles by
      immunohistochemistry and gel electrophoresis.
AB  - In this study we compared the immunohistochemically quantified fiber type area
      with the myosin heavy chain (MyHC) contents of a bundle of fibers from a human
      masticatory muscle. The total cross-sectional areas were determined
      immunohistochemically for the three major fiber types (I, IIA, and IIX) in
      bundles of fibers (n=42) taken from the anterior and posterior belly of the human
      digastric muscle (n=7). The relative MyHC contents of the same fiber bundles were
      determined electrophoretically (MyHC-I, -IIA, and -IIX; anterior, 32%, 35%, and
      33%; posterior, 39%, 42%, and 19%) and compared with the immunohistochemical data
      (MyHC-I, -IIA, and -IIX; anterior, 32%, 31%, and 37%; posterior, 39%, 45%, and
      15%). No significant differences were seen in the mean fiber type distribution
      between the two techniques; the correlation coefficient ranged from 0.71 to 0.96.
      The correlation coefficient was higher for MyHC type I and MyHC type IIX than for
      MyHC type IIA. The MyHC contents of single fibers taken from the posterior belly
      indicated that many fibers in this belly co-express MyHC-IIA and MyHC-IIX.
      Despite the presence of these hybrid fibers, the correspondence between both
      methods was relatively large.

PMID- 12502761
TI  - Isolation of bovine retinal pigment epithelial cells using adhesion to agarose:
      demonstration of cellular and regional heterogeneity.
AB  - The retinal pigment epithelium (RPE) shows cell heterogeneity in morphology and
      enzymatic activity. Routine isolation procedures for RPE cells may reduce
      enzymatic activity and prevent the quantification of regional enzymatic
      differences in vivo. We developed a new technique for the isolation of RPE cells
      based on adhesion of the cells to agarose. The morphology of the isolated cells
      resembled that of RPE cells in vivo. The cells were viable in the dye exclusion
      test and showed a histochemical staining pattern as RPE cells in vivo. With this
      technique, quantitative regional differences in the enzymatic activities were
      detected.

PMID- 12502762
TI  - Localization of EP24.15, a major liver kininase.
AB  - The liver is important for the kallikrein-kinin system modulation. This system
      plays a role in the inflammatory cascade with anticoagulant, profibrinolytic, and
      anti-adhesive attributes. The metalloendopeptidase EP24.15 is a major hepatic
      kininase. We studied the tissue distribution and subcellular localization of this
      enzyme in rat liver by cell fractionation and immunohistochemistry. Our results
      showed that EP24.15 is predominant in the soluble fraction of the liver
      homogenate and is present in the cytoplasm of hepatocytes, particularly in the
      perivenous zone (Z3). This localization is relevant because most hepatotoxin
      induced necrosis, as well as ischemic hepatocellular injury, is predominant in
      Z3.

PMID- 12502763
TI  - An improved protocol of biotinylated tyramine-based immunohistochemistry
      minimizing nonspecific background staining.
AB  - An immunohistochemical method using biotinyl tyramine was recently introduced to
      amplify weak staining signals. Despite its high sensitivity, however, tyramine
      based immunostaining has been limited by its increased background staining. In
      this study, to develop an improved protocol of biotinyl tyramine-based
      immunohistochemistry minimizing the background staining, we determined which
      staining steps lead to the nonspecific reaction and the most appropriate blocking
      agents for background-provoking steps. Trypton casein peptone and distilled water
      with Tween-20 were shown to be most effective as a blocking agent and a rinsing
      solution, respectively. In conclusion, we developed an optimized protocol for
      biotinyl tyramine-based immunohistochemistry with minimal background staining.

PMID- 12502764
TI  - Neurohormonal and glutamatergic neuronal control of the cardioarterial valves in
      the isopod crustacean Bathynomus doederleini.
AB  - The heart of Bathynomus doederleini gives rise to an anterior median artery
      (AMA), one pair of anterior lateral arteries (ALAs) and five pairs of lateral
      arteries (LAs). Cardioarterial valves are located at the junctions between the
      heart and arteries, each composed of a pair of muscular flaps. All valves of the
      AMA and the ALAs receive valve excitatory (constrictor) nerves (VEs). The valves
      of the ALAs receive dual innervation from both constrictor and inhibitor
      (dilator) nerves, while the valves of the AMA receive innervation from a
      constrictor nerve alone. The effects of candidate neurohormones on cardioarterial
      valves were examined by measuring the pressure in each artery at which haemolymph
      flows out of the heart through the valve. Serotonin, octopamine, norepinephrine,
      glutamate (Glu) and proctolin constricted the cardioarterial valves and thus
      decreased the arterial pressure in all the arteries. Dopamine also decreased the
      arterial pressure of arteries except for the ALAs, in which pressure was
      increased. Among the neurohormones exerting excitatory effects on the valves,
      only Glu depolarized the membrane potential of valve muscle cells. The
      glutamatergic agonists kainate and quisqualate also depolarized the valve muscle
      cells of the AMA. Excitatory junctional potentials produced in the valves of the
      AMA in response to the stimulation of a VE were blocked by the glutamatergic
      antagonists Joro spider toxin and MK-801. Glu is the likeliest candidate for a
      neurotransmitter for the VEs.

PMID- 12502765
TI  - Inhibitory motor neurones supply body wall muscles in the locust abdomen.
AB  - Inhibitory motor neurones in the abdominal ganglia of the locust Locusta
      migratoria were identified by combining extra- and intracellular
      electrophysiology, labelling of motor neurones by peripheral nerve backfills, and
      immunocytochemistry directed against the inhibitory transmitter gamma
      aminobutyric acid. The fifth and sixth abdominal ganglia were studied in
      particular detail, although general findings were verified in all other abdominal
      segments. In each abdominal ganglion half, there are two inhibitory motor
      neurones, CIa and CIb, which supply dorsal (CIa) and ventral (CIb) longitudinal
      muscles. Their cell bodies are located in the next anterior ganglion to where the
      axons leave the ventral nerve cord via nerve 1. Both inhibitors have
      contralateral somata in the posterior ventral soma cortex, looping primary
      neurites and bilateral dorsal arborisations. There are homonomous (segmentally
      homologous) motor neurones in the fused abdominal neuromeres, the thoracic
      ganglia, and at least the third subesophageal neuromere. These body wall
      inhibitors are distinctly different from the limb muscle inhibitors, CI(1-3),
      described previously. This is signified, for example, by the fact that both types
      of inhibitory motor neurones coexist in the prothoracic segment and innervate leg
      and body wall muscles, respectively.

PMID- 12502766
TI  - Transvascular and intravascular fluid transport in the rainbow trout: revisiting
      Starling's forces, the secondary circulation and interstitial compliance.
AB  - The kinetics of transvascular fluid transport across fish capillaries and
      redistribution of fluids between intravascular compartments in intact fish are
      unknown. Cannulae were placed in the dorsal aorta (DA) and caudal vein (CV) of
      rainbow trout Oncorhynchus mykiss (mass 0.45-0.85 kg) and the fish
      spleenectomized. The following day a peristaltic pump was fitted to complete the
      extracorporeal arterio-venous circulation. Hematocrit (Hct) was monitored in
      unanesthetized fish either manually, by collecting blood from the extracorporeal
      loop at 5 min intervals for a period of 1 h (groups 1 and 2), or continuously
      (instantaneously) with an impedance flow-cell inserted in the aortic cannula
      (group 3). Fish in group 1 were volume expanded by injecting a volume of saline
      (0.9 g% NaCl; SI) or trout plasma (PI) equivalent to 40% of the plasma volume. In
      group 2, 20% or 35% of the blood volume was removed, and in group 3, 35% of the
      blood volume was removed. Plasma volume (Vp) was calculated from an assumed blood
      volume of 35 ml kg(-1) and the Hct. Vp declined mono-exponentially after SI with
      a half-time of 6.8 min and Vp reached a new steady state at 28.1 ml kg(-1); 30%
      of the injected volume remained in the vasculature. Volume recovery after PI was
      also mono-exponential, but slower (half-time=15.4 min) than SI, whereas the
      steady-state Vp (27.3 ml kg(-1)) was similar and 30% of the injected volume
      remained in the vasculature. Thus the presence of plasma proteins delayed fluid
      efflux from the vasculature, but did not affect the volume lost. Transvascular
      fluid filtration coefficients calculated from this data were 5.5 (SI) and 4.5 ml
      mmHg(-1) kg(-1) min(-1) (PI), and interstitial compliance was 11.8 (SI) and 9.7
      ml mmHg(-1) kg(-1) (PI). The rate of volume recovery after 20% or 35% hemorrhage
      was independent of the hemorrhage volume (half-time=13.3 and 15.1 min,
      respectively) and similar to the half-time of PI, indicating that protein-rich
      interstitial fluid is returned to the vasculature. There is a nearly
      instantaneous change in Hct that occurs during the hemorrhage period; it is
      dependent on hemorrhage duration and volume and not associated with the
      subsequent mono-exponential recovery. This initial response is best explained by
      a rapid fluid shift from a large-volume (approximately 40% of total blood
      volume), low-hematocrit (less than half of systemic Hct) microcirculation into
      the higher-hematocrit macrocirculation. These studies are consistent with
      transcapillary fluid flux across a barrier that is highly permeable to protein,
      and cannot be explained by fluid shift between primary and secondary
      circulations, or by transcapilllary flux across a capillary bed that is
      impermeable to plasma proteins. The results support the hypothesis that whole
      body reflection coefficients in trout are very low and that plasma oncotic
      pressure is not a determinant of transcapillary fluid balance. They also show
      that both transvascular and intravascular fluid movements are important effectors
      of central volume homeostasis.

PMID- 12502767
TI  - Localization of the vacuolar-type ATPase in swimbladder gas gland cells of the
      European eel (Anguilla anguilla).
AB  - The vacuolar ATPase is a multifunctional enzyme that consists of several
      subunits. Subunit B is part of the catalytic domain of the enzyme and is present
      in two isoforms in fish as well as in mammals. Possibly, these two isoforms -
      vatB1 (kidney isoform) and vatB2 (brain isoform) - serve different functions. A
      localization of the two isoforms was attempted in swimbladder gas gland cells of
      the European eel Anguilla anguilla by immunohistochemistry. Two antibodies were
      produced by immunization of rabbits with synthetic peptides. Specificity of the
      antibodies, on the one hand, an isoform-specific antibody for vatB1 and, on the
      other hand, an antibody that recognizes both isoforms (vatB1 and vatB2), was
      confirmed by western blot analysis using recombinant proteins produced in a
      bacterial expression system. The immunohistochemical localization with the
      antibody directed against both isoforms of the B subunit revealed a positive
      staining in apical membranes of swimbladder gas gland cells as well as in the
      basolateral membranes. Significant staining was observed in vesicles located near
      the apical membrane. Staining with the vatB1-specific antibody resulted in a
      similar picture in the apical region of the cells. In contrast to the staining
      with the first antibody, only a poor signal was observed in the basal region. The
      nature of the vesicles in the apical region of the gas gland cells was determined
      by using an antibody directed against surfactant protein D.

PMID- 12502768
TI  - Endogenous and exogenous ice-nucleating agents constrain supercooling in the
      hatchling painted turtle.
AB  - Hatchlings of the painted turtle (Chrysemys picta) commonly hibernate in their
      shallow, natal nests. Survival at temperatures below the limit of freeze
      tolerance (approximately -4 degrees C) apparently depends on their ability to
      remain supercooled, and, whereas previous studies have reported that supercooling
      capacity improves markedly with cold acclimation, the mechanistic basis for this
      change is incompletely understood. We report that the crystallization temperature
      (T(c)) of recently hatched (summer) turtles acclimated to 22 degrees C and reared
      on a substratum of vermiculite or nesting soil was approximately 5 degrees C
      higher than the T(c) determined for turtles acclimated to 4 degrees C and tested
      in winter. This increase in supercooling capacity coincided with elimination of
      substratum (and, in fewer cases, eggshell) that the hatchlings had ingested;
      however, this association was not necessarily causal because turtles reared on a
      paper-covered substratum did not ingest exogenous matter but nevertheless showed
      a similar increase in supercooling capacity. Our results for turtles reared on
      paper revealed that seasonal development of supercooling capacity fundamentally
      requires elimination of ice-nucleating agents (INA) of endogenous origin: summer
      turtles, but not winter turtles, produced feces (perhaps derived from residual
      yolk) that expressed ice-nucleating activity. Ingestion of vermiculite or
      eggshell, which had modest ice-nucleating activity, had no effect on the T(c),
      whereas ingestion of nesting soil, which contained two classes of potent INA,
      markedly reduced the supercooling capacity of summer turtles. This effect
      persisted long after the turtles had purged their guts of soil particles, because
      the T(c) of winter turtles reared on nesting soil (mean +/- S.E.M.=-11.6+/-1.4
      degrees C) was approximately 6 degrees C higher than the T(c) of winter turtles
      reared on vermiculite or paper. Experiments in which winter turtles were fed INA
      commonly found in nesting soil showed that water-soluble, organic agents can
      remain fully active for at least one month. Such INA may account for the limited
      supercooling capacity (T(c) approximately -7.5 degrees C) we found in turtles
      overwintering in natural nests and may therefore pose a formidable challenge to
      the winter survival of hatchling C. picta.

PMID- 12502769
TI  - On-line venous oxygen tensions in rainbow trout during graded exercise at two
      acclimation temperatures.
AB  - For most teleost fish, the majority of the myocardial oxygen supply is provided
      by the oxygen reserve remaining in venous blood after other tissues have
      extracted oxygen. We examined the effect of graded exercise and water temperature
      on this venous blood oxygen supply to the heart (termed the cardiac circulation)
      by performing novel on-line measurements of venous partial pressure of oxygen
      (Pv(O(2))) using a fibreoptic micro-optode implanted in the ductus Cuvier of
      rainbow trout (Oncorhynchus mykiss). As expected, Pv(O(2)) decreased
      progressively and significantly as swimming velocity approached the critical
      swimming speed (U(crit)). Unsteady swimming behaviours during the graded
      exercise, however, caused abrupt and generally short-lived decreases in Pv(O(2)).
      For the cold-acclimated (6-10 degrees C) fish, Pv(O(2)) reached a minimum plateau
      value of 15.3+/-3.7 torr (1 torr=133.3 Pa) before U(crit) was reached, and so
      increased swimming effort near to U(crit) did not reduce Pv(O(2)) further. Warm
      acclimated fish had a significantly higher Pv(O(2)) (28.9+/-3.5 torr) at U(crit).
      Despite this difference in the Pv(O(2)) at U(crit), we estimated that there was
      little difference between warm- and cold-acclimated fish in terms of oxygen
      supply in the cardiac circulation because of a right-shift in the haemoglobin
      oxygen dissociation curve at warm temperatures. Furthermore, although Pv(O(2))
      decreased significantly at U(crit), our estimates suggest that the expected
      increase in cardiac output would easily maintain the oxygen supply in venous
      blood at a level similar to that found in resting fish. Although unsteady
      swimming behaviours decreased Pv(O(2)), unsteady swimming rarely decreased the
      minimum Pv(O(2)) value observed at U(crit) by more than 10%. The findings are
      discussed in terms of a threshold Pv(O(2)) required to maintain adequate rates of
      oxygen diffusion from the cardiac circulation to the myocardial tissues.

PMID- 12502770
TI  - Magnet-induced disorientation in hatchling loggerhead sea turtles.
AB  - Laboratory experiments have indicated that hatchling loggerhead sea turtles
      (Caretta caretta) are able to establish and maintain courses using information
      from the Earth's magnetic field. In previous experiments, turtles were tested in
      relatively uniform magnetic fields generated by large coil systems surrounding an
      orientation arena. In this study, we investigated the orientation behavior of
      hatchlings with either magnets or magnetically inert brass bars attached to their
      carapaces. Control turtles (with brass bars) oriented significantly towards the
      east whereas turtles bearing magnets were not significantly oriented as a group.
      The two distributions were statistically different. These results indicate that
      magnetic orientation behavior of hatchling sea turtles can be disrupted by
      attaching a small magnet to the carapace. This finding may prove useful both in
      field experiments and in efforts to localize magnetoreceptors.

PMID- 12502771
TI  - Condition, prolonged swimming performance and muscle metabolic capacities of cod
      Gadus morhua.
AB  - This study evaluated the link between swimming endurance and condition of
      Atlantic cod Gadus morhua that had been fed or starved during the 16 weeks
      preceding the tests, and assessed whether muscle metabolic capacities explain
      such links. The condition factor [(somatic mass x fork length(-3))x100] of
      starved cod was 0.54+/-0.1 whereas that of fed cod was 0.81+/-0.1. In white and
      red muscle, we measured four glycolytic enzymes: phosphofructokinase (PFK),
      pyruvate kinase (PK), creatine kinase (CK) and lactate dehydrogenase (LDH), two
      mitochondrial enzymes: cytochrome c oxidase (CCO) and citrate synthase (CS), a
      biosynthetic enzyme, nucleoside diphosphate kinase (NDPK), glycogen and protein
      levels and water content. Muscle samples were taken at three positions along the
      length of the fish; starvation affected the metabolic capacities of white muscle
      more than those of red muscle. The levels of glycolytic enzymes and glycogen
      changed more in white than red muscle during starvation. Both in fed and starved
      cod, muscle metabolic capacities varied with position along the fish; starvation
      reduced this longitudinal variation more in white than red muscle. In white
      muscle of fed cod, the glycolytic enzyme levels increased from head to tail,
      while in starved cod this longitudinal variation disappeared. In red muscle
      mitochondrial enzyme levels were highest in the caudal sample, but fewer
      differences were found for glycolytic enzymes. Swimming endurance was markedly
      affected by fish condition, with starved fish swimming only 30% of the time (and
      distance) of fed fish. This endurance was closely linked with the number of burst
      coast movements during the test and the activity of CCO and LDH in white muscle.
      The number of burst-coast movements was significantly linked with condition
      factor and PFK activity in caudal red muscle and gill arch mass. Our data
      indicated that cod use both glycolytic and oxidative capacities to support
      endurance swimming. Furthermore, swimming endurance is linked with the metabolic
      capacities of red and white muscle.

PMID- 12502772
TI  - Volumetric and ionic responses of goldfish hepatocytes to anisotonic exposure and
      energetic limitation.
AB  - The relationship between cell volume and K(+) transmembrane fluxes of goldfish
      (Carassius auratus) hepatocytes exposed to anisotonic conditions or energetic
      limitation was studied and compared with the response of hepatocytes from trout
      (Oncorhynchus mykiss) and rat (Rattus rattus). Cell volume was studied by video-
      and fluorescence microscopy, while K(+) fluxes were assessed by measuring
      unidirectional (86)Rb(+) fluxes. In trout and rat hepatocytes, hyposmotic (180
      mosmoll(-1)) exposure at pH 7.45 caused cell swelling followed by a regulatory
      volume decrease (RVD), a response reported to be mediated by net efflux of KCl
      and osmotically obliged water. By contrast, goldfish hepatocytes swelled but
      showed no RVD under these conditions. Although in goldfish hepatocytes a net
      ((86)Rb(+))K(+) efflux could be activated by N-ethylmaleimide, this flux was not,
      or only partially, activated by hyposmotic swelling (120-180 mosmoll(-1)).
      Blockage of glycolysis by iodoacetic acid (IAA) did not alter cell volume in
      goldfish hepatocytes, whereas in the presence of cyanide (CN(-)), an inhibitor of
      oxidative phosphorylation, or CN(-) plus IAA (CN(-)+IAA), cell volume decreased
      by 3-7%. Although in goldfish hepatocytes, energetic limitation had no effect on
      ((86)Rb(+))K(+) efflux, ((86)Rb(+))K(+) influx decreased by 57-66% in the
      presence of CN(-) and CN(-)+IAA but was not significantly altered by IAA alone.
      Intracellular K(+) loss after 20 min of exposure to CN(-) and CN(-)+IAA amounted
      to only 3% of the total intracellular K(+). Collectively, these observations
      suggest that goldfish hepatocytes, unlike hepatocytes of anoxia-intolerant
      species, avoid a decoupling of transmembrane K(+) fluxes in response to an
      osmotic challenge. This may underlie both the inability of swollen cells to
      undergo RVD but also the capability of anoxic cells to maintain intracellular
      K(+) concentrations that are almost unaltered, thereby prolonging cell survival.

PMID- 12502773
TI  - Mechanoreceptors involved in the hindwing-evoked escape behaviour in cricket,
      Gryllus bimaculatus.
AB  - Mechanoreceptors involved in the escape jumping evoked by hindwing stimulation
      have been investigated in the field cricket Gryllus bimaculatus. By partial
      ablation of the hindwing, we found that a mechanosensory system relevant to the
      escape behaviour was localized on specific veins of the hindwing tip. Scanning
      electron microscopy revealed three types of mechanoreceptive sensillae on the
      corresponding region. Based on their morphology, type I and type III sensillae
      were judged to be trichoid and chaetic sensillae, respectively. Type II sensillae
      were newly found in this study, having a twisted shaft with a socket-like
      structure at its base. They existed almost exclusively on the tip and middle
      regions of the hindwing. The conduction velocity of type II units was
      significantly smaller than that of type I units. One cycle of sinusoidal
      deflection of a single type II sensilla at frequencies in the range of 10-120 Hz
      caused the sensory unit to discharge a single or a few spikes that were not
      directly correlated with any specific direction of hair movement nor specific
      deflection angle. The response probability decreased with the stimulus frequency
      to be less than 0.1 at 0.2 Hz. The results suggest that type II sensillae would
      serve as contact mechanoreceptors with a low-cut filter property to obtain
      general information on the presence of stimuli on the hindwing tip rather than
      specific information on their precise positioning or movement.

PMID- 12502774
TI  - The influence of beacon-aiming on the routes of wood ants.
AB  - Many insects have an innate propensity to approach conspicuous objects. We
      explore how such beacon aiming determines the shape of a wood ant's habitual
      route. We find that a single large black cylinder within an arena biases the
      route taken by ants as they run from a start position at one end of the arena to
      reach a feeder at the other. Ants learn a stable route with the first segment of
      their trajectory aimed at the cylinder, which becomes an intermediate goal on the
      way to the feeder. When in occasional tests the cylinder is removed or displaced,
      ants head for the usual site of the cylinder. They also aim for the same site
      when the cylinder is removed and the ant's normal start position is changed. This
      behaviour suggests that visual features of the arena are learnt from the vantage
      point of the cylinder and that this stored snapshot guides the ant to that site.
      Ants thus reinforce their ability to reach the cylinder by learning other visual
      features in their surroundings that can also steer them to its location. The use
      of beacon aiming in fixing routes has several benefits. Because the same path
      will be traversed on every trial, beacon aiming facilitates the acquisition of
      routes. Beacon aiming also increases the robustness of learnt routes: ants
      straying from the route will be attracted to the closest beacon and so regain
      their habitual paths.

PMID- 12502775
TI  - Lactate efflux from sarcolemmal vesicles isolated from rainbow trout Oncorhynchus
      mykiss white muscle is via simple diffusion.
AB  - Lactic acid is produced as an end product of glycolysis in rainbow trout white
      muscle following exhaustive exercise. The metabolically produced lactic acid
      causes an intramuscular acidosis that must be cleared, either via net transport
      out of the muscle or by conversion to glycogen, thereby replenishing the muscle
      energy store. Trout muscle has been shown to retain lactate and utilise it as a
      substrate for in situ glycogen resynthesis. The giant sarcolemmal vesicle
      preparation was used to characterise the potential for lactate loss from white
      muscle of rainbow trout. Minimal lactate loss was expected due to the requirement
      within the intramuscular compartment of lactate for glycogen resynthesis. The
      sarcolemma was found to be highly resistant to lactate loss, with efflux rates
      approximately 500-fold lower than influx rates [0.049+/-0.006 nmol mg(-1) min(-1)
      (N=21) versus 26.4+/-6.3 nmol mg(-1) min(-1) (N=5), respectively, at 25 mmol l(
      1) lactate concentration]. Lactate efflux was linear over the range 10-250 mmol
      l(-1) lactate, and greatest under conditions when intravesicular pH was lower
      than extravesicular pH, but was unaffected by alpha-cyano-4-hydroxycinnamate, a
      known inhibitor of lactate transport. These results suggest that lactate is
      relatively impermeant to the trout white muscle membrane and any lactate loss
      occurs via passive diffusion. This resistance to lactate diffusion can explain
      why trout muscle retains lactate post-exercise, despite transmembrane gradients
      that should favour net efflux.

PMID- 12502776
TI  - Localization and characterization of phenamil-sensitive Na+ influx in isolated
      rainbow trout gill epithelial cells.
AB  - Percoll density-gradient separation, combined with peanut lectin agglutinin (PNA)
      binding and magnetic bead separation, was used to separate dispersed fish gill
      cells into sub-populations. Functional characterization of each of the sub
      populations was performed to determine which displayed acid-activated phenamil-
      and bafilomycin-sensitive Na(+) uptake. Analysis of the mechanism(s) of (22)Na(+)
      influx was performed in control and acid-activated (addition of 10 mmoll(-1)
      proprionic acid) cells using a variety of Na(+) transport inhibitors (ouabain,
      phenamil, HOE-694 and bumetanide) and a V-type ATPase inhibitor (bafilomycin). We
      found that cells migrating to a 1.03-1.05 g ml(-1) Percoll interface [pavement
      cells (PVCs)] possessed the lowest rates of Na(+) uptake and that influx was
      unchanged during either bafilomycin (10 nmoll(-1)) treatment or internal
      acidification with addition of proprionic acid (10 mmoll(-1)). Mitochondria-rich
      (MR) cells that migrated to the 1.05-1.09 g ml(-1) interface of the Percoll
      gradient demonstrated acidification-activated bafilomycin and phenamil-sensitive
      Na(+) influx. Further separation of the MR fraction into PNA(+) and PNA(-)
      fractions using magnetic separation demonstrated that only the PNA(-) cells
      (alpha-MR cells) demonstrated phenamil-and bafilomycin-sensitive acid-activated
      (22)Na(+) uptake. We confirm the coupling of a V-type H(+)-ATPase with phenamil
      sensitive Na(+) uptake activity and conclude that high-density alpha-MR cells
      function in branchial Na(+) uptake in freshwater fish.

PMID- 12502777
TI  - Cloning of a muscle-specific calpain from the American lobster Homarus
      americanus: expression associated with muscle atrophy and restoration during
      moulting.
AB  - A cDNA (1977 bp) encoding a crustacean calpain (Ha-CalpM; GenBank accession no.
      AY124009) was isolated from a lobster fast muscle cDNA library. The open reading
      frame specified a 575-amino acid (aa) polypeptide with an estimated mass of 66.3
      kDa. Ha-CalpM shared high identity with other calpains in the cysteine proteinase
      domain (domain II; aa 111-396) and domain III (aa 397-575), but most of the N
      terminal domain (domain I; aa 1-110) was highly divergent. Domain II contained
      the cysteine, histidine and asparagine triad essential for catalysis, as well as
      two conserved aspartate residues that bind Ca(2+). In domain III an acidic loop
      in the C2-like region, which mediates Ca(2+)-dependent phospholipid binding, had
      an expanded stretch of 17 aspartate residues. Ha-CalpM was classified as a non-EF
      hand calpain, as it lacked domain IV, a calmodulin-like region containing five EF
      hand motifs. Northern blot analysis, relative reverse transcription-polymerase
      chain reaction (RT-PCR) and real-time PCR showed that Ha-CalpM was highly
      expressed in skeletal muscles, but at much lower levels in heart, digestive
      gland, intestine, integument, gill, nerve cord/thoracic ganglion and antennal
      gland. An antibody raised against a unique N-terminal sequence recognized a 62
      kDa isoform in cutter claw and crusher claw closer muscles and a 68 kDa isoform
      in deep abdominal muscle. Ha-CalpM was distributed throughout the cytoplasm, as
      well as in some nuclei, of muscle fibers. Purification of Ha-CalpM showed that
      the 62 kDa and 68 kDa isoforms co-eluted from gel filtration and ion exchange
      columns at positions consistent with those of previously described Ca(2+)
      dependent proteinase III (CDP III; 59 kDa). Ha-CalpM mRNA and protein did not
      change during the moulting cycle. The muscle-specific expression of Ha-CalpM and
      the ability of Ha-CalpM/CDP III to degrade myofibrillar proteins suggest that it
      is involved in restructuring and/or maintaining contractile structures in
      crustacean skeletal muscle.

PMID- 12502778
TI  - Transcriptional initiation under conditions of anoxia-induced quiescence in
      mitochondria from Artemia franciscana embryos.
AB  - In response to anoxia, embryos of the brine shrimp Artemia franciscana are able
      coordinately to downregulate metabolism to levels low enough to permit survival
      for several years at room temperature. In addition to dramatic decreases in free
      ATP levels and heat production, intracellular pH drops from 7.8 to 6.3 overnight.
      Use of isolated mitochondria to study transcriptional responses to anoxia offers
      several advantages: (1). the localized nature of transcript initiation,
      processing and degradation, all of which may be followed in organello; (2). the
      relatively simple cis- and trans-machinery involved and (3). the ability to
      provide relevant physiological treatments in vitro. In response to anoxic
      incubation of embryos in vivo for 4 h followed by anoxic mitochondrial isolation
      and anoxic transcription assay at pH 6.4, a significant decrease in overall UTP
      incorporation (77%) was seen after 30 min relative to normoxic, pH 7.9 controls.
      A less severe inhibition of transcription under anoxia (52%) was observed
      compared with controls when pH was raised to 7.9. Similarly, under normoxia, the
      incubation at low pH (6.4) reduced transcription by 59%. Ribonuclease protection
      assays showed that the contribution of in vitro initiation during the assay fell
      from 78% at pH 7.9 to approximately 32% at pH 6.4 under either normoxic or anoxic
      conditions. DNA footprinting of putative transcriptional promoters revealed
      proteins at regular intervals upstream of the 12S rRNA in the control region,
      which previously had been indirectly inferred to contain promoters for H-strand
      transcription. The area between 1230 and 12065 contains a sequence in the
      tRNA(leu) gene believed to bind the transcription termination factor mTERF or
      TERM, and we provide the first evidence that this sequence is protein-bound in A.
      franciscana. However, our hypothesis that initiation is reduced at low pH because
      of a change in DNA binding by mitochondrial transcription factors was not
      confirmed. We propose that regulation of initiation may be mediated by covalent
      modification or by protein-protein interactions not detected by footprinting.

PMID- 12502779
TI  - The blood volumes of the primary and secondary circulatory system in the Atlantic
      cod Gadus morhua L, using plasma bound Evans Blue and compartmental analysis.
AB  - The volume of the primary (PCS) and secondary (SCS) circulatory system in the
      Atlantic cod Gadus morhua was determined using a modified dye dilution technique.
      Cod (N=10) were chronically cannulated in the second afferent branchial artery
      with PE-50 tubing. Evans Blue dye was bound to harvested fish plasma at a
      concentration of 1 mg dye ml(-1) plasma, and injected at a concentration of 1 mg
      kg(-1) body mass. Serial sampling from the cannula produced a dye dilution curve,
      which could be described by a double exponential decay equation. Curve analysis
      enabled the calculation of the primary circulatory and total distribution volume.
      The difference between these volumes is assumed to be the volume of the SCS. From
      the dilution curve, it was also possible to calculate flow rates between and
      within the systems. The results of these experiments suggest a plasma volume in
      the PCS of 3.42+/-0.89 ml 100 g(-1) body mass, and in the SCS of 1.68+/-0.35 ml
      100 g(-1) body mass (mean +/- S.D.) or approximately 50% that of the PCS. Flow
      rates to the SCS were calculated as 2.7% of the resting cardiac output. There was
      an allometric relationship between body mass and blood volumes. Increasing
      condition factor showed a tendency towards smaller blood volumes of the PCS,
      expressed as percentage body mass, but this was not evident for the volume of the
      SCS.

PMID- 12502780
TI  - Cloning of rainbow trout (Oncorhynchus mykiss) alpha-actin, myosin regulatory
      light chain genes and the 5'-flanking region of alpha-tropomyosin. Functional
      assessment of promoters.
AB  - We report PCR cloning of rainbow trout alpha-actin (alpha-OnmyAct), myosin
      regulatory light chain (OnmyMLC2) genes and the 5'-flanking region of alpha
      tropomyosin (alpha-OnmyTM). Being expressed in skeletal and cardiac muscle, alpha
      OnmyAct was a predominant isoform in trunk muscle of adult rainbow trout. Exon
      structure of this gene was identical to all known vertebrate skeletal and to some
      of the cardiac alpha-Act genes. Two distinct OnmyMLC2 promoters were cloned and
      both included transposon-like sequences. The coding part of OnmyMLC2 consisted of
      seven exons whose length was typical for vertebrate MLC2 genes. The upstream
      regions of alpha-OnmyAct and OnmyMLC2 included a TATA box and a number of
      putative regulatory motifs (E-boxes in all three sequences and CArG-boxes in
      alpha-OnmyAct), whereas there were no canonical motifs in the alpha-OnmyTM
      promoter. LacZ reporter gene was fused with the 5'-flanking regions of alpha
      OnmyAct, two OnmyMLC2 genes and alpha-OnmyTM promoters. These constructs were
      transferred into rainbow trout eggs. At the stage of 39 somite pairs, LacZ
      reporter was detected in the myotomes, neural plate and neural crest, brain and
      yolk syncytial layer of all analysed embryos. alpha-OnmyTMLacZ was also expressed
      in the heart. Functionality of promoters and the alpha-OnmyAct terminator was
      confirmed in rainbow trout primary embryonic cell cultures. We cloned rainbow
      trout glucose transporter type I (OnmyGLUT1) into vectors including the alpha
      OnmyAct and OnmyMLC2 promoters and the alpha-SkAct terminator. Recombinant
      OnmyGLUT1 transcripts were detected in rainbow trout embryos during
      somitogenesis.

PMID- 12502781
TI  - Dietary sodium inhibits aqueous copper uptake in rainbow trout (Oncorhynchus
      mykiss).
AB  - Ours is the first study to demonstrate an influence of dietary sodium on
      waterborne copper uptake in fish. We examined possible interactions between
      dietary sodium and the response of freshwater rainbow trout (Oncorhynchus mykiss)
      to waterborne copper in light of recent evidence of interactions between sodium
      and copper metabolism in the gills. Trout were maintained for 6 days on one of
      four diets of increasing sodium concentration (0.25 mmol g(-1), 0.51 mmol g(-1),
      0.76 mmol g(-1) and 1.27 mmol g(-1), which corresponds to 0.6%, 1.2%, 1.8% and 3%
      sodium by mass, respectively). At the end of 7 days, fish were exposed for 6 h to
      waterborne copper spiked with (64)Cu to determine if the dietary sodium affected
      responses to a subsequent short-term waterborne copper exposure. The radiotracer
      allowed us to distinguish between Cu occurring in fish tissues before the
      experiment and 'newly accumulated' Cu arising from the experimental exposure.
      Dietary sodium concentrations of 1.8% or 3% reduced newly accumulated copper
      concentrations in gill (from 93.9 ng g(-1) in control to 38.9 ng g(-1) and 20.0
      ng g(-1) in fish fed 1.8% or 3% Na(+)-supplemented diets, respectively), liver
      (from 64.3 ng g(-1) to 23.1 ng g(-1) and 7.5 ng g(-1), respectively), kidney
      (from 29.3 ng g(-1) to 11.7 ng g(-1) and 7.8 ng g(-1), respectively), plasma
      (from 64.7 ng g(-1) to 21.5 ng g(-1) and 10.7 ng g(-1), respectively) and gut
      (from 6.8 ng g(-1) to 3.4 ng g(-1) and 2.2 ng g(-1), respectively) by 50.0-88.2%.
      The 3% Na(+)-supplemented diets also increased plasma and gut sodium
      concentrations by 38.1% (from 137.1 micromol g(-1) to 189.3 micromol g(-1)) and
      104.3% (from 56.5 micromol g(-1) to 115.4 micromol g(-1)), respectively, relative
      to fish maintained on untreated diets. Whole body uptake rates of both sodium and
      copper were significantly reduced, and highly correlated (r=0.97) with one
      another, in fish fed high-sodium diets relative to controls. Moreover, sodium
      efflux was 12% and 38% higher in fish fed 1.8% and 3% sodium-enriched diets,
      respectively. Fish fed high-sodium diets also drank more water, but the
      contribution of drinking to waterborne copper uptake was negligible. From these
      results, we speculate that, at least in part, aqueous sodium and copper share a
      common branchial uptake route, probably through an apical sodium channel.
      According to this hypothesis, as the channel is downregulated with increasing
      internal sodium concentrations, both sodium and copper uptake from the water are
      inhibited.

PMID- 12502782
TI  - Electrophysiology of posterior, NaCl-absorbing gills of Chasmagnathus granulatus:
      rapid responses to osmotic variations.
AB  - In the present study, the influence of short-term osmotic variations on some
      electrophysiological properties related to NaCl absorption across posterior gills
      of Chasmagnathus granulatus was investigated. The transepithelial potential
      difference (V(te)) of isolated and perfused gills increased significantly when
      hyposmotic saline (699 mosmol l(-1)) was used instead of isosmotic solution (1045
      mosmol l(-1)). A reduction of the concentration of Na(+) or Cl(-) at constant
      osmolarity did not produce any change in V(te). Transepithelial short-circuit
      current (I(sc)) and conductance (G(te)), measured with split gill lamellae
      mounted in a modified Ussing chamber, also increased after changing to hyposmotic
      salines (I(sc): from -89.0+/-40.8 microA cm(-2) to -179.3+/-37.0 microA cm(-2);
      G(te): from 40.5+/-16.9 mS cm(-2) to 47.3+/-15.8 mS cm(-2)). The observed effects
      of reduced osmolarity were fast, reversible and gradually dependent on the
      magnitude of the osmotic variation. The activity of the Na(+)/K(+)-ATPase
      increased significantly after perfusion with hyposmotic saline, from 18.73+/-6.35
      micromol P(i) h(-1) mg(-1) to 41.84+/-14.54 micromol P(i) h(-1) mg(-1).
      Theophylline maintained part of the elevated V(te) induced by hyposmotic saline,
      suggesting that an increased cellular cyclic AMP level is involved in the
      response to reduced osmolarity. In summary, the results indicate that the
      hemolymph osmolarity regulates active transbranchial NaCl absorption by
      modulating the activity of the basolateral Na(+)/K(+)-ATPase and by changing a
      conductive pathway, probably at the apical membrane.

PMID- 12502783
TI  - PPNDS is an agonist, not an antagonist, for the ATP receptor of Paramecium.
AB  - Paramecium represents a simple, eukaryotic model system to study the cellular
      effects of some neuroactive drugs. They respond to the agonist beta,gamma
      methylene ATP with a transient depolarizing receptor potential, Ca(2+)-based
      action potentials and repetitive bouts of forward and backward swimming called
      'avoiding reactions' (AR). In vivo [(32)P]ATP binding assays showed saturable
      [(32)P]ATP binding with an apparent K(d) of approximately 23 nmol l(-1).
      Prolonged (15 min) exposure to 25 micro mol l(-1) beta,gamma-methylene ATP caused
      behavioral adaptation and losses of AR, ATP receptor potentials and [(32)P]ATP
      binding. While screening various ATP receptor inhibitors, we found that the P2X1
      'antagonist' pyridoxal-phosphate naphthylazo-nitro-disulfate (PPNDS) is actually
      an agonist, producing the same responses as beta,gamma-methylene ATP. [(32)P]ATP
      binding assays suggest that both agonists may bind to the same site as
      [(32)P]ATP. Cross-adaptation is also seen between PPNDS and beta,gamma-methylene
      ATP in terms of losses in AR, depolarizing receptor potentials and [(32)P]ATP
      binding. We conclude that the inhibition caused by PPNDS in Paramecium is due to
      agonist-induced desensitization. Either this represents a unique new class of ATP
      receptors, in which PPNDS is an agonist instead of an antagonist, or PPNDS (and
      other drugs like it) may actually be an agonist in many other cell types in which
      prolonged exposure is necessary for inhibition.

PMID- 12502784
TI  - Structural basis and prediction of substrate specificity in protein
      serine/threonine kinases.
AB  - The large number of protein kinases makes it impractical to determine their
      specificities and substrates experimentally. Using the available crystal
      structures, molecular modeling, and sequence analyses of kinases and substrates,
      we developed a set of rules governing the binding of a heptapeptide substrate
      motif (surrounding the phosphorylation site) to the kinase and implemented these
      rules in a web-interfaced program for automated prediction of optimal substrate
      peptides, taking only the amino acid sequence of a protein kinase as input. We
      show the utility of the method by analyzing yeast cell cycle control and DNA
      damage checkpoint pathways. Our method is the only available predictive method
      generally applicable for identifying possible substrate proteins for protein
      serinethreonine kinases and helps in silico construction of signaling pathways.
      The accuracy of prediction is comparable to the accuracy of data from systematic
      large-scale experimental approaches.

PMID- 12502785
TI  - The role of neutralizing antibodies for mouse mammary tumor virus transmission
      and mammary cancer development.
AB  - Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers
      and a lifelong neutralizing Ab response. We show that removal of the draining
      lymph node after establishment of the germinal center reaction led to complete
      loss of neutralizing Abs despite comparable infection levels in peripheral
      lymphocytes. Importantly, in the absence of neutralization, only the exocrine
      organs mammary gland, salivary gland, pancreas, and skin showed strikingly
      increased infection, resulting in accelerated mammary tumor development.
      Induction of stronger neutralization did not influence chronic infection levels
      of peripheral lymphoid organs but strongly inhibited mammary gland infection and
      virus transmission to the next generation. Taken together, we provide evidence
      that a tight equilibrium in virus neutralization allows limited infection of
      exocrine organs and controls cancer development in susceptible mouse strains.
      These experiments show that a strong neutralizing Ab response induced after
      infection is not able to control lymphoid MMTV infection. Strong neutralization,
      however, is capable of blocking amplification of mammary gland infection, tumor
      development, and virus transmission to the next generation. The results also
      indicate a role of neutralization in natural resistance to MMTV infection.

PMID- 12502786
TI  - A macromolecular complex of beta 2 adrenergic receptor, CFTR, and
      ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA.
AB  - It has been demonstrated previously that both the cystic fibrosis transmembrane
      conductance regulator (CFTR) and beta(2) adrenergic receptor (beta(2)AR) can bind
      ezrinradixinmoesin-binding phosphoprotein 50 (EBP50, also referred to as NHERF)
      through their PDZ motifs. Here, we show that beta(2) is the major adrenergic
      receptor isoform expressed in airway epithelia and that it colocalizes with CFTR
      at the apical membrane. beta(2)AR stimulation increases CFTR activity, in airway
      epithelial cells, that is glybenclamide sensitive. Deletion of the PDZ motif from
      CFTR uncouples the channel from the receptor both physically and functionally.
      This uncoupling is specific to the beta(2)AR receptor and does not affect CFTR
      coupling to other receptors (e.g., adenosine receptor pathway). Biochemical
      studies demonstrate the existence of a macromolecular complex involving CFTR
      EBP50-beta(2)AR through PDZ-based interactions. Assembly of the complex is
      regulated by PKA-dependent phosphorylation. Deleting the regulatory domain of
      CFTR abolishes PKA regulation of complex assembly. This report summarizes a
      macromolecular signaling complex involving CFTR, the implications of which may be
      relevant to CFTR-dysfunction diseases.

PMID- 12502787
TI  - Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA
      is a transcellular PPARgamma agonist.
AB  - Lysophosphatidic acid (LPA) is a pluripotent lipid mediator acting through plasma
      membrane-associated LPA(x) receptors that transduce many, but not all, of its
      effects. We identify peroxisome proliferator-activated receptor gamma (PPARgamma)
      as an intracellular receptor for LPA. The transcription factor PPARgamma is
      activated by several lipid ligands, but agonists derived from physiologic
      signaling pathways are unknown. We show that LPA, but not its precursor
      phosphatidic acid, displaces the drug rosiglitazone from the ligand-binding
      pocket of PPARgamma. LPA and novel LPA analogs we made stimulated expression of a
      PPAR-responsive element reporter and the endogenous PPARgamma-controlled gene
      CD36, and induced monocyte lipid accumulation from oxidized low-density
      lipoprotein via the CD36 scavenger receptor. The synthetic LPA analogs were
      effective PPARgamma agonists, but were poor ones for LPA(1), LPA(2), or LPA(3)
      receptor transfected cells. Transfection studies in yeast, which lack nuclear
      hormone and LPA(x) receptors, show that LPA directly activates PPARgamma. A major
      growth factor of serum is LPA generated by thrombin-activated platelets, and
      media from activated platelets stimulated PPARgamma function in transfected
      RAW264.7 macrophages. This function was suppressed by ectopic LPA-acyltransferase
      expression. LPA is a physiologic PPARgamma ligand, placing PPARgamma in a
      signaling pathway, and PPARgamma is the first intracellular receptor identified
      for LPA. Moreover, LPA produced by stimulated plasma platelets activates
      PPARgamma in nucleated cells.

PMID- 12502788
TI  - Evidence for the widespread coupling of alternative splicing and nonsense
      mediated mRNA decay in humans.
AB  - To better understand the role of alternative splicing, we conducted a large-scale
      analysis of reliable alternative isoforms of known human genes. Each isoform was
      classified according to its splice pattern and supporting evidence. We found that
      one-third of the alternative transcripts examined contain premature termination
      codons, and most persist even after rigorous filtering by multiple methods. These
      transcripts are apparent targets of nonsense-mediated mRNA decay (NMD), a
      surveillance mechanism that selectively degrades nonsense mRNAs. Several of these
      transcripts are from genes for which alternative splicing is known to regulate
      protein expression by generating alternate isoforms that are differentially
      subjected to NMD. We propose that regulated unproductive splicing and translation
      (RUST), through the coupling of alternative splicing and NMD, may be a pervasive,
      underappreciated means of regulating protein expression.

PMID- 12502789
TI  - Phenotypic effects of familial amyotrophic lateral sclerosis mutant Sod alleles
      in transgenic Drosophila.
AB  - A subset of patients suffering from familial amyotrophic lateral sclerosis (FALS)
      exhibit point mutations in the gene encoding Cu-Zn superoxide dismutase
      [superoxide:superoxide oxidoreductase, EC (SOD)]. The human wild-type and five
      FALS Sod mutant transgenes were introduced into the fruit fly, Drosophila
      melanogaster, in a Cu-Zn Sod null background. Sod null flies had dramatically
      decreased life span, glutathione and methionine content, fertility, locomotor
      activity, and resistance to hyperoxic stress, compared with wild-type controls.
      All of these phenotypic manifestations were rescued fully by a single human wild
      type allele, expressing 5-10% of wild-type SOD activity. Full recovery of wild
      type life span was also observed when human mutant and wild-type alleles were
      placed together in the fly Sod null background. The FALS Sod mutations alone
      caused a recessive phenotype, usually involving low or undetectable levels of SOD
      activity, in which: (i) full restoration of the wild-type phenotype was observed
      among young adults, and (ii) older adults exhibited a sudden increase in
      oxidative stress, accompanied by physiological impairment of abrupt onset, and
      followed by premature death. Thus, the minimal SOD activity associated with the
      FALS Sod mutations appears to determine longevity, not by chronically increasing
      oxidative stress, but by limiting the time in which a viable redox environment
      can be maintained. However, the dominant gain of function by mutant SOD, which
      occurs in human patients and in the transgenic mouse model of FALS, is not
      observed in Drosophila.

PMID- 12502790
TI  - Invariant representations of visual patterns in a temporal population code.
AB  - Mammalian visual systems are characterized by their ability to recognize stimuli
      invariant to various transformations. Here, we investigate the hypothesis that
      this ability is achieved by the temporal encoding of visual stimuli. By using a
      model of a cortical network, we show that this encoding is invariant to several
      transformations and robust with respect to stimulus variability. Furthermore, we
      show that the proposed model provides a rapid encoding, in accordance with recent
      physiological results. Taking into account properties of primary visual cortex,
      the application of the encoding scheme to an enhanced network demonstrates
      favorable scaling and high performance in a task humans excel at.

PMID- 12502791
TI  - Mitotic clonal expansion: a synchronous process required for adipogenesis.
AB  - When induced to differentiate, growth-arrested 3T3-L1 preadipocytes synchronously
      reenter the cell cycle and undergo mitotic clonal expansion (MCE) followed by
      expression of genes that produce the adipocyte phenotype. The preadipocytes
      traverse the G(1)S checkpoint synchronously as evidenced by the
      expressionactivation of cdk2-cyclin-EA, turnover of p27kip1, hyperphosphorylation
      of Rb, translocation of cyclin D(1) from nuclei to cytoplasm and GSK-3beta from
      cytoplasm to nuclei, and incorporation of [(3)H]thymidine into DNA. As the cells
      cross the G(1)S checkpoint, CEBPbeta acquires DNA-binding activity, initiating a
      cascade of transcriptional activation that culminates in the expression of
      adipocyte proteins. The mitogen-activated protein kinaseextracellular signal
      regulated kinase kinase (MEK) inhibitor PD98059 delays, but does not block, MCE
      and differentiation, the extent of the delay causing a comparable delay in the
      expression of cell-cycle markers, MCE, and adipogenesis. The more potent and
      specific MEK inhibitor UO126 and the cyclin-dependent kinase inhibitor
      roscovitine, which inhibit the cell cycle at different points, block MCE,
      expression of cell cycle and adipocyte markers, as well as adipogenesis. These
      results show that MCE is a prerequisite for differentiation of 3T3-L1
      preadipocytes into adipocytes.

PMID- 12502793
TI  - Chemical nature of nitric oxide storage forms in rat vascular tissue.
AB  - Endothelial NO production results in local formation of adducts that may act as
      storage forms of NO. Because little is known about their chemical nature,
      concentrations, and possible role in vascular biology, we sought to characterize
      those species basally present in rat aorta, using two independent approaches. In
      the first approach, tissue homogenates were analyzed by using chemiluminescence-
      and ion-chromatography-based techniques that allow trace-level quantification of
      NO-related compounds in complex biological matrices. In the second approach, NO
      stores were characterized by their ability to release NO when illuminated with
      light and subsequently relax vascular smooth muscle (photorelaxation). The latter
      included a careful assessment of action spectra for photorelaxation, taking into
      account the light-scattering properties of the tissue and the storage depletion
      rates induced by exposure to controlled levels of light. Biochemical analyses
      revealed that aortic tissues contained 10 +/- 1 microM nitrite, 42 +/- 7 microM
      nitrate, 40 +/- 6 nM S-nitroso, and 33 +/- 6 nM N-nitroso compounds (n = 4-8).
      The functional data obtained suggest that the NO photolytically released in the
      tissue originated from species with photophysical properties similar to those
      reported for low-molecular-weight S-nitrosothiols, as well as from nitrite. The
      relative contribution of these potential NO stores to the extent of
      photorelaxation was consistent with their concentrations detected biochemically
      in vascular tissue when their photoactivity was taken into account. We conclude
      that intravascular nitroso species and nitrite both have the potential to release
      physiologically relevant quantities of NO independent of enzymatic control by NO
      synthase.

PMID- 12502794
TI  - Sequence variations in the public human genome data reflect a bottlenecked
      population history.
AB  - Single-nucleotide polymorphisms (SNPs) constitute the great majority of
      variations in the human genome, and as heritable variable landmarks they are
      useful markers for disease mapping and resolving population structure. Redundant
      coverage in overlaps of large-insert genomic clones, sequenced as part of the
      Human Genome Project, comprises a quarter of the genome, and it is representative
      in terms of base compositional and functional sequence features. We mined these
      regions to produce 500,000 high-confidence SNP candidates as a uniform resource
      for describing nucleotide diversity and its regional variation within the genome.
      Distributions of marker density observed at different overlap length scales under
      a model of recombination and population size change show that the history of the
      population represented by the public genome sequence is one of collapse followed
      by a recent phase of mild size recovery. The inferred times of collapse and
      recovery are Upper Paleolithic, in agreement with archaeological evidence of the
      initial modern human colonization of Europe.

PMID- 12502795
TI  - Transcriptional mapping and genomic analysis of the cardiac atria and ventricles.
AB  - The atria and ventricles of the heart have distinct development, structure, and
      physiology. However, only a few of the genes that underlie the differences
      between these tissues are known. We used a murine cardiac cDNA microarray to
      identify genes differentially expressed in the atria and ventricles. The
      reliability of these findings is supported by highly concordant repetition of
      hybridization, recognition of previously known atrial and ventricular isoforms of
      contractile proteins, and confirmation of results by quantitative PCR and in situ
      hybridization. We examined the most differentially regulated genes for
      evolutionarily conserved noncoding sequences and found that atrial-expressed
      genes have more predicted myocyte enhancer factor-2 (MEF2) binding sites than
      ventricle-predominant genes. We confirmed that messages for MEF2 family members
      are more abundant in the atria, as are their protein products. Moreover, the
      activity of a transgenic reporter construct for MEF2 activity is preferentially
      upregulated in the atria in response to hypertrophic stimuli. This study provides
      a greater understanding of the molecular differences between atria and ventricles
      and establishes the framework for an anatomically detailed evaluation of cardiac
      transcriptional regulation.

PMID- 12502797
TI  - Role of the transmembrane domains of prM and E proteins in the formation of
      yellow fever virus envelope.
AB  - Flavivirus envelope proteins have been shown to play a major role in virus
      assembly. These proteins are anchored into cellular and viral membranes by their
      C-terminal domain. These domains are composed of two hydrophobic stretches
      separated by a short hydrophilic segment containing at least one charged residue.
      We investigated the role of the transmembrane domains of prM and E in the
      envelope formation of the flavivirus yellow fever virus (YFV). Alanine scanning
      insertion mutagenesis has been used to examine the role of the transmembrane
      domains of prM and E in YFV subviral particle formation. Most of the insertions
      had a dramatic effect on the release of YFV subviral particles. Some of these
      mutations were introduced into the viral genome. The ability of these mutant
      viruses to produce infectious particles was severely reduced. The alanine
      insertions did not affect prM-E heterodimerization. In addition, replacement of
      the charged residues present in the middle of the transmembrane domains had no
      effect on subviral particle release. Taken together, these data indicate that the
      transmembrane domains of prM and E play a crucial role in the biogenesis of YFV
      envelope. In addition, these data indicate some differences between the
      transmembrane domains of the hepaciviruses and the flaviviruses.

PMID- 12502798
TI  - Functional interaction of nuclear factor y and sp1 is required for activation of
      the epstein-barr virus C promoter.
AB  - Two Epstein-Barr virus (EBV) latent cycle promoters, Wp and Cp, are activated
      sequentially during virus-induced transformation of primary B lymphocytes.
      Immediately postinfection, viral transcription initiates from Wp, leading to
      expression of EBV nuclear antigen 2 (EBNA2) and EBNA5. Within 36 h, there is a
      switch in promoter usage from Wp to the upstream Cp, which leads to expression of
      EBNA1 to EBNA6. EBNA2 appears to be required for the Wp-to-Cp switch, but the
      switching mechanism is not fully understood at the molecular level. In a previous
      investigation we showed that there is an EBNA2-independent activity of reporter
      constructs containing deletion fragments of Cp in B-lymphoid cell lines, and we
      demonstrated that Cp activity is highly dependent on several cellular
      transcription factors, including nuclear factor Y (NF-Y) and Sp1. In the present
      work, we analyzed the effect of NF-Y on Cp activity in greater detail. We
      demonstrate that (i) a dominant negative analogue of NF-Y abolishes Cp activity,
      (ii) NF-Y and Sp1 costimulate Cp, and (iii) the oriPI-EBNA1-induced
      transactivation of Cp requires concomitant expression of NF-Y and Sp1, although
      additional factors seem necessary for optimal activation. Furthermore, using the
      lymphoblastoid cell line EREB2-5, in which EBNA2 function is regulated by
      estrogen, we demonstrate that inactivation of EBNA2 results in decreased
      expression of NF-Y and down-regulation of Cp. On reconstitution of the EBNA2
      function, the cells enter the cell cycle, NF-Y levels increase, and a concomitant
      Wp-to-Cp switch occurs. Taken together, our results suggest that NF-Y is
      essential for Cp activation and that up-regulation of NF-Y may contribute to a
      successful Wp-to-Cp switch during B-cell transformation.

PMID- 12502799
TI  - Conformational changes in the spike glycoprotein of murine coronavirus are
      induced at 37 degrees C either by soluble murine CEACAM1 receptors or by pH 8.
AB  - The spike glycoprotein (S) of the murine coronavirus mouse hepatitis virus (MHV)
      binds to viral murine CEACAM receptor glycoproteins and causes membrane fusion.
      On virions, the 180-kDa S glycoprotein of the MHV-A59 strain can be cleaved by
      trypsin to form the 90-kDa N-terminal receptor-binding subunit (S1) and the 90
      kDa membrane-anchored fusion subunit (S2). Incubation of virions with purified,
      soluble CEACAM1a receptor proteins at 37 degrees C and pH 6.5 neutralizes virus
      infectivity (B. D. Zelus, D. R. Wessner, R. K. Williams, M. N. Pensiero, F. T.
      Phibbs, M. deSouza, G. S. Dveksler, and K. V. Holmes, J. Virol. 72:7237-7244,
      1998). We used liposome flotation and protease sensitivity assays to investigate
      the mechanism of receptor-induced, temperature-dependent virus neutralization.
      After incubation with soluble receptor at 37 degrees C and pH 6.5, virions became
      hydrophobic and bound to liposomes. Receptor binding induced a profound,
      apparently irreversible conformational change in S on the viral envelope that
      allowed S2, but not S1, to be degraded by trypsin at 4 degrees C. Various murine
      CEACAM proteins triggered conformational changes in S on recombinant MHV strains
      expressing S glycoproteins of MHV-A59 or MHV-4 (MHV-JHM) with the same
      specificities as seen for virus neutralization and virus-receptor activities.
      Increased hydrophobicity of virions and conformational change in S2 of MHV-A59
      could also be induced by incubating virions at pH 8 and 37 degrees C, without
      soluble receptor. Surprisingly, the S protein of recombinant MHV-A59 virions with
      a mutation, H716D, that precluded cleavage between S1 and S2 could also be
      triggered to undergo a conformational change at 37 degrees C by soluble receptor
      at neutral pH or by pH 8 alone. A novel 120-kDa subunit was formed following
      incubation of the receptor-triggered S(A59)H716D virions with trypsin at 4
      degrees C. The data show that unlike class 1 fusion glycoproteins of other
      enveloped viruses, the murine coronavirus S protein can be triggered to a
      membrane-binding conformation at 37 degrees C either by soluble receptor at
      neutral pH or by alkaline pH alone, without requiring previous activation by
      cleavage between S1 and S2.

PMID- 12502800
TI  - The N-terminal domain of the murine coronavirus spike glycoprotein determines the
      CEACAM1 receptor specificity of the virus strain.
AB  - Using isogenic recombinant murine coronaviruses expressing wild-type murine
      hepatitis virus strain 4 (MHV-4) or MHV-A59 spike glycoproteins or chimeric MHV
      4/MHV-A59 spike glycoproteins, we have demonstrated the biological functionality
      of the N-terminus of the spike, encompassing the receptor binding domain (RBD).
      We have used two assays, one an in vitro liposome binding assay and the other a
      tissue culture replication assay. The liposome binding assay shows that
      interaction of the receptor with spikes on virions at 37 degrees C causes a
      conformational change that makes the virions hydrophobic so that they bind to
      liposomes (B. D. Zelus, J. H. Schickli, D. M. Blau, S. R. Weiss, and K. V.
      Holmes, J. Virol. 77: 830-840, 2003). Recombinant viruses with spikes containing
      the RBD of either MHV-A59 or MHV-4 readily associated with liposomes at 37
      degrees C in the presence of soluble mCEACAM1(a), except for S(4)R, which
      expresses the entire wild-type MHV-4 spike and associated only inefficiently with
      liposomes following incubation with soluble mCEACAM1(a). In contrast, soluble
      mCEACAM1(b) allowed viruses with the MHV-A59 RBD to associate with liposomes more
      efficiently than did viruses with the MHV-4 RBD. In the second assay, which
      requires virus entry and replication, all recombinant viruses replicated
      efficiently in BHK cells expressing mCEACAM1(a). In BHK cells expressing
      mCEACAM1(b), only viruses expressing chimeric spikes with the MHV-A59 RBD could
      replicate, while replication of viruses expressing chimeric spikes with the MHV-4
      RBD was undetectable. Despite having the MHV-4 RBD, S(4)R replicated in BHK cells
      expressing mCEACAM1(b); this is most probably due to spread via CEACAM1 receptor
      independent cell-to-cell fusion, an activity displayed only by S(4)R among the
      recombinant viruses studied here. These data suggest that the RBD domain and the
      rest of the spike must coevolve to optimize function in viral entry and spread.

PMID- 12502801
TI  - Reactivation of lytic replication from B cells latently infected with Epstein
      Barr virus occurs with high S-phase cyclin-dependent kinase activity while
      inhibiting cellular DNA replication.
AB  - Productive infection and replication of herpesviruses usually occurs in growth
      arrested cells, but there has been no direct evidence in the case of Epstein-Barr
      virus (EBV), since an efficient lytic replication system without external stimuli
      does not exist for the virus. Expression of the EBV lytic-switch transactivator
      BZLF1 protein in EBV-negative epithelial tumor cell lines, however, is known to
      arrest the cell cycle in G(0)/G(1) by induction of the tumor suppressor protein
      p53 and the cyclin-dependent kinase (CDK) inhibitors p21(WAF-1/CIP-1) and p27(KIP
      1), followed by the accumulation of a hypophosphorylated form of the Rb protein.
      In order to determine the effect of the onset of lytic viral replication on
      cellular events in latently EBV-infected B LCLs, a tightly controlled induction
      system of the EBV lytic-replication program by inducible BZLF1 protein expression
      was established in B95-8 cells. The induction of lytic replication completely
      arrested cell cycle progression and cellular DNA replication. Surprisingly, the
      levels of p53, p21(WAF-1/CIP-1), and p27(KIP-1) were constant before and after
      induction of the lytic program, indicating that the cell cycle arrest induced by
      the lytic program is not mediated through p53 and the CDK inhibitors.
      Furthermore, although cellular DNA replication was blocked, elevation of cyclin
      E/A expression and accumulation of hyperphosphorylated forms of Rb protein were
      observed, a post-G(1)/S phase characteristic of cells. Thus, while the EBV lytic
      program promoted specific cell cycle-associated activities involved in the
      progression from G(1) to S phase, it inhibited cellular DNA synthesis. Such
      cellular conditions appear to especially favor viral lytic replication.

PMID- 12502802
TI  - The clearance of hepatitis C virus infection in chimpanzees may not necessarily
      correlate with the appearance of acquired immunity.
AB  - Clearance of hepatitis C virus (HCV) infection in humans and chimpanzees is
      thought to be associated with the induction of strong T-cell responses. We
      studied four chimpanzees infected with HCV derived from an infectious full-length
      HCV genotype 1b cDNA. Two of the chimpanzees cleared the infection to
      undetectable levels for more than 12 months of follow-up; the other two became
      persistently infected. Detailed analyses of HCV-specific immune responses were
      performed during the courses of infection in these chimpanzees. Only weak and
      transient T helper responses were detected during the acute phase in all four
      chimpanzees. A comparison of the frequency of gamma interferon (IFN-gamma)
      producing CD4(+) and CD8(+) T cells in peripheral blood by ELISpot assay did not
      reveal any correlation between viral clearance and T-cell responses. In addition,
      analyses of IFN-gamma, IFN-alpha, and interleukin-4 mRNA levels in liver
      biopsies, presumably indicative of intrahepatic T-cell responses, revealed no
      distinct pattern in these chimpanzees with respect to infection outcome. The
      present study suggests that the outcome of HCV infection in chimpanzees is not
      necessarily attributable to HCV sequence variation and that chimpanzees may
      recover from HCV infection by mechanisms other than the induction of readily
      detectable HCV-specific T-cell responses.

PMID- 12502803
TI  - Frequent reassortment among influenza C viruses.
AB  - In a 9-year survey from December 1990 to December 1999 in Sendai City, Japan, we
      succeeded in isolating a total of 45 strains of influenza C virus. These 45
      strains were isolated in clusters within 4 months in a year, especially from
      winter to early summer. Previous studies of the hemagglutinin-esterase genes of
      various influenza C virus isolates revealed the existence of five distinct virus
      lineages (Aichi/1/81-, Yamagata/26/81-, Mississippi/80-, Sao Paulo/82-, and
      Kanagawa/1/76-related lineage) in Japan between 1970 and the early 1990s (Y.
      Matsuzaki, K. Mizuta, H. Kimura, K. Sugawara, E. Tsuchiya, H. Suzuki, S. Hongo,
      and K. Nakamura, J. Gen. Virol. 81:1447-1452, 2000). Antigenic and genetic
      analyses of the 45 strains showed that they could be divided into these five
      virus lineages and a few antigenic groups were cocirculating in Sendai City. In
      1990 and 1991 the dominant antigenic group was the Aichi/1/81 virus group, and in
      1992 it was Yamagata/26/81 virus group. The Mississippi/80 virus group was
      isolated from 1993 to 1996, and the Yamagata/26/81 virus group reemerged in 1996
      and continued to circulate until 1999. This finding led us to a speculation that
      the replacement of the dominant antigenic groups had occurred by immune selection
      within the human population in the restricted area. Phylogenetic analysis of
      seven RNA segments showed that 44 viruses among the 45 strains isolated in our
      surveillance work were reassortant viruses that have various genome compositions
      distinguishable from those of the reference strains of the each lineage. This
      observation suggests that the reassortment between two different influenza C
      virus strains occurs frequently in nature and the genome composition of influenza
      C viruses may influence their ability to spread in humans.

PMID- 12502804
TI  - Association between virus-specific T-cell responses and plasma viral load in
      human immunodeficiency virus type 1 subtype C infection.
AB  - Virus-specific T-cell immune responses are important in restraint of human
      immunodeficiency virus type 1 (HIV-1) replication and control of disease. Plasma
      viral load is a key determinant of disease progression and infectiousness in HIV
      infection. Although HIV-1 subtype C (HIV-1C) is the predominant virus in the AIDS
      epidemic worldwide, the relationship between HIV-1C-specific T-cell immune
      responses and plasma viral load has not been elucidated. In the present study we
      address (i) the association between the level of plasma viral load and virus
      specific immune responses to different HIV-1C proteins and their subregions and
      (ii) the specifics of correlation between plasma viral load and T-cell responses
      within the major histocompatibility complex (MHC) class I HLA supertypes. Virus
      specific immune responses in the natural course of HIV-1C infection were analyzed
      in the gamma interferon (IFN-gamma)-enzyme-linked immunospot assay by using
      synthetic overlapping peptides corresponding to the HIV-1C consensus sequence.
      For Gag p24, a correlation was seen between better T-cell responses and lower
      plasma viral load. For Nef, an opposite trend was observed where a higher T-cell
      response was more likely to be associated with a higher viral load. At the level
      of the HLA supertypes, a lower viral load was associated with higher T-cell
      responses to Gag p24 within the HLA A2, A24, B27, and B58 supertypes, in contrast
      to the absence of such a correlation within the HLA B44 supertype. The present
      study demonstrated differential correlations (or trends to correlation) in
      various HIV-1C proteins, suggesting (i) an important role of the HIV-1C Gag p24
      specific immune responses in control of viremia and (ii) more rapid viral escape
      from immune responses to Nef with no restraint of plasma viral load. Correlations
      between the level of IFN-gamma-secreting T cells and viral load within the MHC
      class I HLA supertypes should be considered in HIV vaccine design and efficacy
      trials.

PMID- 12502805
TI  - Biochemical and genetic studies of the VPg uridylylation reaction catalyzed by
      the RNA polymerase of poliovirus.
AB  - The first step in poliovirus (PV) RNA synthesis is the covalent linkage of UMP to
      the terminal protein VPg. This reaction can be studied in vitro with two
      different assays. The simpler assay is based on a poly(A) template and requires
      synthetic VPg, purified RNA polymerase 3D(pol), UTP, and a divalent cation. The
      other assay uses specific viral sequences [cre(2C)] as a template for VPg
      uridylylation and requires the addition of proteinase 3CD(pro). Using one or both
      of these assays, we analyzed the VPg specificities and metal requirements of the
      uridylylation reactions. We determined the effects of single and double amino
      acid substitutions in VPg on the abilities of the peptides to serve as substrates
      for 3D(pol). Mutations in VPg, which interfered with uridylylation in vitro, were
      found to abolish viral growth. A chimeric PV containing the VPg of human
      rhinovirus 14 (HRV14) was viable, but substitutions of HRV2 and HRV89 VPgs for PV
      VPg were lethal. Of the three rhinoviral VPgs tested, only the HRV14 peptide was
      found to function as a substrate for PV1(M) 3D(pol) in vitro. We also examined
      the metal specificity of the VPg uridylylation reaction on a poly(A) template.
      Our results show a strong preference of the RNA polymerase for Mn(2+) as a
      cofactor compared to Mg(2+) or other divalent cations.

PMID- 12502806
TI  - The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is
      required at the stage of nuclear egress.
AB  - Human cytomegalovirus encodes an unusual protein kinase, UL97, that activates the
      established antiviral drug ganciclovir and is specifically inhibited by a new
      antiviral drug, maribavir. We used maribavir and a UL97 null mutant, which is
      severely deficient in viral replication, to determine what stage of virus
      infection critically requires UL97. Compared with wild-type virus, there was
      little or no decrease in immediate-early gene expression, viral DNA synthesis,
      late gene expression, or packaging of viral DNA into nuclease-resistant
      structures in mutant-infected or maribavir-treated cells under conditions where
      the virus yield was severely impaired. Electron microscopy studies revealed
      similar proportions of various capsid forms, including DNA-containing capsids, in
      the nuclei of wild-type- and mutant-infected cells. However, capsids were rare in
      the cytoplasm of mutant-infected or maribavir-treated cells; the magnitudes of
      these decreases in cytoplasmic capsids were similar to those for virus yield.
      Thus, genetic and pharmacological evidence indicates that UL97 is required at the
      stage of infection when nucleocapsids exit from the nucleus (nuclear egress), and
      this poorly understood stage of virus infection can be targeted by antiviral
      drugs. Understanding UL97 function and maribavir action should help elucidate
      this interesting biological process and help identify new antiviral drug targets
      for an important pathogen in immunocompromised patients.

PMID- 12502807
TI  - Adenovirus type 5 DNA binding protein stimulates binding of DNA polymerase to the
      replication origin.
AB  - The adenovirus (Ad) DNA-binding protein (DBP) is essential for the elongation
      phase of Ad DNA replication by unwinding the template in an ATP-independent
      fashion, employing its capacity to form multimers. DBP also enhances the rate of
      initiation, with the highest levels obtained at low concentrations of Ad DNA
      polymerase (Pol). Here, we show that stimulation of initiation depends on the
      template conformation. Maximal stimulation, up to 15-fold, is observed on double
      stranded or viral TP-containing origins. The stimulation is reduced on partially
      single-stranded origins and DBP does not enhance initiation any more once the
      origin is completely unwound. This suggests a role for DBP in origin unwinding
      that is comparable to its unwinding capacity during elongation. However, mutant
      DBP proteins defective in unwinding and elongation can still enhance initiation
      on ds templates. DBP also stimulates the binding of nuclear factor I (NFI) to the
      origin and lowers the K(m) for coupling of the first nucleotide to the precursor
      terminal protein by Pol. Mobility shift experiments reveal that DBP stimulates
      the binding of Pol on double-stranded origin and nonorigin DNA but not on single
      stranded DNA. This effect is specific for DBP and is also seen with other DNA
      Pols. Our results suggest that, rather than by origin unwinding, DBP enhances
      initiation by modulating the origin conformation such that DNA Pol can bind more
      efficiently.

PMID- 12502808
TI  - Ubiquitin ligase activities of Bombyx mori nucleopolyhedrovirus RING finger
      proteins.
AB  - The genome of Bombyx mori nucleopolyhedrovirus (BmNPV) is predicted to contain
      six RING finger proteins: IAP1, ORF35, IAP2, CG30, IE2, and PE38. Several other
      members of the RING finger family have recently been shown to have the ubiquitin
      ligase (E3) activity. We thus examined whether BmNPV RING finger proteins have
      the E3 activity. In vitro ubiquitination assay with the rabbit reticulocyte
      lysates and BmNPV RING finger proteins fused with maltose-binding protein (MBP)
      showed that four of them (IAP2, IE2, PE38, and CG30) were polyubiquitinated in
      the presence of zinc ion. Furthermore, MBP-IAP2, MBP-IE2, and MBP-PE38 were able
      to reconstitute ubiquitination activity in cooperation with the Ubc4/5 subfamily
      of ubiquitin-conjugating enzymes. Mutational analysis also showed that
      ubiquitination activity of MBP-IAP2, MBP-IE2, and MBP-PE38 were dependent on
      their RING finger motif. Therefore, these results suggest that IAP2, IE2, and
      PE38 may function as E3 enzymes during BmNPV infection.

PMID- 12502809
TI  - Identification of gp120 binding sites on CXCR4 by using CD4-independent human
      immunodeficiency virus type 2 Env proteins.
AB  - Human immunodeficiency virus (HIV) and simian (SIV) immunodeficiency virus entry
      is mediated by binding of the viral envelope glycoprotein (Env) to CD4 and
      chemokine receptors, CCR5 and/or CXCR4. CD4 induces extensive conformational
      changes that expose and/or induce formation of a chemokine receptor binding site
      on gp120. CD4-independent Env's of HIV type 1 (HIV-1), HIV-2, and SIV have been
      identified that exhibit exposed chemokine receptor binding sites and can bind
      directly to CCR5 or CXCR4 in the absence of CD4. While many studies have examined
      determinants for gp120-CCR5 binding, analysis of gp120-CXCR4 binding has been
      hindered by the apparently lower affinity of this interaction for X4-tropic HIV-1
      isolates. We show here that gp120 proteins from two CD4-independent HIV-2 Env's,
      VCP and ROD/B, bind directly to CXCR4 with an apparently high affinity. By use of
      CXCR4 N-terminal deletion constructs, CXCR4-CXCR2 chimeras, and human-rat CXCR4
      chimeras, binding determinants were shown to reside in the amino (N) terminus,
      extracellular loop 2 (ECL2), and ECL3. Alanine-scanning mutagenesis of charged
      residues, tyrosines, and phenylalanines in extracellular CXCR4 domains implicated
      multiple amino acids in the N terminus (E14/E15, D20, Y21, and D22), ECL2 (D187,
      R188, F189, Y190, and D193), and ECL3 (D262, E268, E277, and E282) in binding,
      although minor differences were noted between VCP and ROD/B. However, mutations
      in CXCR4 that markedly reduced binding did not necessarily hinder cell-cell
      fusion by VCP or ROD/B, especially in the presence of CD4. These gp120 proteins
      will be useful in dissecting determinants for CXCR4 binding and Env triggering
      and in evaluating pharmacologic inhibitors of the gp120-CXCR4 interaction.

PMID- 12502810
TI  - The multimerization of hantavirus nucleocapsid protein depends on type-specific
      epitopes.
AB  - Multimerization of the Hantaan virus nucleocapsid protein (NP) in Hantaan virus
      infected Vero E6 cells was observed in a competitive enzyme-linked immunosorbent
      assay (ELISA). Recombinant and truncated NPs of Hantaan, Seoul, and Dobrava
      viruses lacking the N-terminal 49 amino acids were also detected as multimers.
      Although truncated NPs of Hantaan virus lacking the N-terminal 154 amino acids
      existed as a monomer, those of Seoul and Dobrava formed multimers. The
      multimerized truncated NP antigens of Seoul and Dobrava viruses could detect
      serotype-specific antibodies, whereas the monomeric truncated NP antigen of
      Hantaan virus lacking the N-terminal 154 amino acids could not, suggesting that a
      hantavirus serotype-specific epitope on the NP results in multimerization. The NP
      NP interaction was also detected by using a yeast two-hybrid assay. Two regions,
      amino acids 100 to 125 (region 1) and amino acids 404 to 429 (region 2), were
      essential for the NP-NP interaction in yeast. The NP of Seoul virus in which the
      tryptophan at amino acid number 119 was replaced by alanine (W119A mutation) did
      not multimerize in the yeast two-hybrid assay, indicating that tryptophan 119 in
      region 1 is important for the NP-NP interaction in yeast. However, W119A mutants
      expressed in mammalian cells were detected as the multimer by using competitive
      ELISA. Similarly, the truncated NP of Seoul virus expressing amino acids 155 to
      429 showed a homologous interaction in a competitive ELISA but not in the yeast
      two-hybrid assay, indicating that the C-terminal region is important for the
      multimerization detected by competitive ELISA. Combined, the results indicate
      that several steps and regions are involved in multimerization of hantavirus NP.

PMID- 12502811
TI  - A protective role of locally administered immunostimulatory CpG
      oligodeoxynucleotide in a mouse model of genital herpes infection.
AB  - Unmethylated CpG dinucleotides in bacterial DNA or synthetic
      oligodeoxynucleotides (ODNs) are known as potent activators of the immune system
      and inducers of several Th1-associated immunomodulatory cytokines. We therefore
      investigated whether such a CpG-containing ODN (CpG ODN) given mucosally in the
      female genital tract could enhance innate immunity and protect against genital
      herpes infection. Groups of C57BL/6 mice were treated intravaginally with either
      CpG ODN or a non-CpG ODN control in the absence of any antigen either 2 days
      before or 4 h after an intravaginal challenge with a normally lethal dose of
      herpes simplex virus type 2 (HSV-2). Mice treated with CpG ODN exhibited
      significantly decreased titers of HSV-2 in their vaginal fluids compared with non
      CpG ODN-treated mice. Furthermore, CpG ODN pretreatment significantly protected
      against development of disease and death compared to non-CpG ODN pretreatment.
      Most strikingly, CpG ODN conferred protection against disease and death even when
      given after the viral challenge. The CpG ODN-induced protection was associated
      with a rapid production of gamma interferon (IFN-gamma), interleukin-12 (IL-12),
      IL-18, and RANTES in the genital tract mucosa following CpG ODN treatment. The
      observed protection appeared to be dependent on IFN-gamma, IL-12, IL-18, and T
      cells, as CpG ODN pretreatment did not confer any significant protection in mice
      deficient in IFN-gamma, IL-12, IL-18, or T cells. Further, a complete protective
      immunity to reinfection was elicited in CpG ODN-treated, HSV-2-challenged mice,
      suggesting a role for mucosally administered CpG ODN in inducing the development
      of an acquired immune response in addition to its potent stimulation of innate
      immunity.

PMID- 12502812
TI  - Human T-cell leukemia virus type 1 envelope-mediated syncytium formation can be
      activated in resistant Mammalian cell lines by a carboxy-terminal truncation of
      the envelope cytoplasmic domain.
AB  - Human T-cell leukemia virus (HTLV) envelope (Env) glycoproteins induce fusion,
      leading to rampant syncytium formation in a broad range of cell lines. Here, we
      identified murine, hamster, canine, and porcine cell lines that are resistant to
      HTLV-1 Env-induced syncytium formation. This resistance was not due to the
      absence of functional receptors for HTLV Env, as these cells were susceptible to
      infection with HTLV Env-pseudotyped virions. As murine leukemia virus (MLV) Env
      and HTLV Env present close structural homologies (F. J. Kim, I. Seiliez, C.
      Denesvre, D. Lavillette, F. L. Cosset, and M. Sitbon, J. Biol. Chem. 275:23417
      23420, 2000), and because activation of syncytium formation by MLV Env generally
      requires cleavage of the R peptide in the cytoplasmic domain of the Env
      transmembrane (TM) component, we assessed whether truncation of the cytoplasmic
      domain of HTLV Env would alleviate this resistance. Indeed, in all resistant cell
      lines, truncation of the last 8 amino acids of the HTLV Env cytoplasmic domain
      (HdC8) was sufficient to overcome resistance to HTLV Env-induced syncytium
      formation. Furthermore, HdC8-mediated cell-to-cell infection titers varied
      according to the target cell lines and could be significantly higher than that
      observed with HTLV Env on HeLa cells. These data indicate that a determinant
      located within the 8 carboxy-terminal cytoplasmic amino acids of TM plays a
      distinct role in HTLV Env-mediated cell-to-cell infection and syncytium
      formation.

PMID- 12502813
TI  - Quantitative detection of hepadnavirus-infected lymphoid cells by in situ PCR
      combined with flow cytometry: implications for the study of occult virus
      persistence.
AB  - The detection of small amounts of viral pathogens in infected cells by classical
      PCR is hampered by a partial loss of virus nucleic acid due to extraction and by
      difficulties in discrimination between truly intracellular virus genome material
      and that possibly adhered to the cell surface. These impediments limit reliable
      identification of virus traces within infected cells, which are typically
      encountered in latent and persistent occult infections. In this study,
      hepadnavirus-specific in situ PCR combined with the enzymatic elimination of
      extracellular virus and flow cytometry permitted detection of viral genomes in
      lymphoid cells without nucleic acid isolation and allowed quantification of
      infected cells during the course of persistent infection with woodchuck hepatitis
      virus (WHV). The validity of the procedure was confirmed by hybridization
      analysis of the in situ-amplified viral sequences. The results showed that
      hepadnavirus can be directly detected within lymphoid cells not only in
      serologically accountable infection, but also years after recovery from viral
      hepatitis and in the course of primary occult virus carriage. Percentages of
      infected peripheral lymphoid cells in symptomatic WHV hepatitis fluctuate between
      3.4 and 20.4% (mean +/- standard error of the mean, 9.6% +/- 1.7%), whereas those
      in persistent, serologically mute WHV infection range from 1.1 to 14.6% (mean +/-
      standard error of the mean, 4.8% +/- 0.8%) (P = 0.005). The data obtained provide
      further evidence that WHV infection continues indefinitely in the lymphatic
      system independently of whether it is symptomatic or concealed. They document
      that hepadnavirus can be detected in a significant proportion of circulating
      lymphoid cells in both immunovirologically apparent as well as occult persistent
      infection.

PMID- 12502814
TI  - Identification of immunodominant epitopes derived from the respiratory syncytial
      virus fusion protein that are recognized by human CD4 T cells.
AB  - Memory CD4 T-cell responses against respiratory syncytial virus (RSV) were
      evaluated in peripheral blood mononuclear cells of healthy blood donors with
      gamma interferon enzyme-linked immunospot (Elispot) assays. RSV-specific
      responses were detected in every donor at levels varying between 0.05 and 0.3% of
      CD4 T cells. For all donors tested, a considerable component of the CD4 T-cell
      response was directed against the fusion (F) protein of RSV. We characterized a
      set of 31 immunodominant antigenic peptides targeted by CD4 T cells in the
      context of the most prevalent HLA class II molecules within the Caucasian
      population. Most antigenic peptides were HLA-DR restricted, whereas two dominant
      DQ peptides were also identified. The antigenic peptides identified were located
      across the entire sequence of the F protein. Several peptides were presented by
      more than one major histocompatibility complex class II molecule. Furthermore,
      most donors recognized several F peptides. Detailed knowledge about
      immunodominant antigenic peptides will facilitate the ability to monitor CD4 T
      cell responses in patients and the measurement of correlates of protection in
      vaccinated subjects.

PMID- 12502815
TI  - Increased mucosal transmission but not enhanced pathogenicity of the CCR5-tropic,
      simian AIDS-inducing simian/human immunodeficiency virus SHIV(SF162P3) maps to
      envelope gp120.
AB  - Through rapid serial transfer in vivo, the chimeric CCR5-tropic simian/human
      immunodeficiency virus SHIV(SF162) evolved from a virus that is nonpathogenic and
      poorly transmissible across the vaginal mucosa to a variant that still maintains
      CCR5 usage but which is now pathogenic and establishes intravaginal infection
      efficiently. To determine whether envelope glycoprotein gp120 is responsible for
      increased pathogenesis and transmissibility of the variant SHIV(SF162P3), we
      cloned and sequenced the dominant envelope gene (encoding P3 gp120) and
      characterized its functions in vitro. Chimeric SHIV(SF162) virus expressing P3
      gp120 of the pathogenic variant, designated SHIV(SF162PC), was also constructed
      and assessed for its pathogenicity and mucosal transmissibility in vivo. We found
      that, compared to wild-type SHIV(SF162) gp120, P3 gp120 conferred in vitro
      neutralization resistance and increased entry efficiency of the virus but was
      compromised in its fusion-inducing capacity. In vivo, SHIV(SF162PC) infected two
      of two and two of three rhesus macaques by the intravenous and intravaginal
      routes, respectively. Nevertheless, although peak viremia reached 10(6) to 10(7)
      RNA copies per ml of plasma in some infected animals and was associated with
      depletion of gut-associated CD4(+) lymphocytes, none of the animals maintained a
      viral set point that would be predictive of progression to disease. Together, the
      data from this study suggest a lack of correlation between entry efficiency and
      cytopathic properties of envelope glycoproteins with viral pathogenicity.
      Furthermore, whereas env gp120 contains the determinant for enhanced mucosal
      transmissibility of SHIV(SF162P3), the determinant(s) of its increased virulence
      may require additional sequence changes in env gp41 and/or maps to other viral
      genes.

PMID- 12502816
TI  - EBNA3A association with RBP-Jkappa down-regulates c-myc and Epstein-Barr virus
      transformed lymphoblast growth.
AB  - Epstein-Barr virus nuclear antigen protein 3A (EBNA3A) is one of four EBNAs (EBNA
      2, EBNALP, EBNA3A, and EBNA3C) through the cellular DNA sequence-specific
      transcription factor RBP-Jkappa/CBF-1/CSL and are essential for conversion of
      primary B lymphocytes to lymphoblastoid cell lines (LCLs). In the present study,
      we investigated the effects of EBNA3A on EBNA2 activation of transcription in the
      IB4 LCL by conditionally overexpressing EBNA3A three- to fivefold. EBNA3A
      overexpression increased EBNA3A association with RBP-Jkappa, did not change
      EBNA3C association with RBP-Jkappa or EBNA or LMP1 expression, decreased EBNA2
      association with RBP-Jkappa, decreased c-myc expression, and caused G(0)/G(1)
      growth arrest with prolonged viability. Expression of the fusion protein MycERTM
      in cells with conditional EBNA3A overexpression restored cell cycle progression
      and caused apoptosis. In contrast, MycER in the same cells without EBNA3A
      overexpression enhanced cell proliferation and did not increase apoptosis. These
      data indicate that EBNA3A overexpression inhibits protection from c-myc-induced
      apoptosis. In assays of EBNA2- and RBP-Jkappa-dependent transcription, EBNA3A
      amino acids 1 to 386 were sufficient for repression equivalent to that by wild
      type EBNA3A, amino acids 1 to 124 were unimportant, amino acids 1 to 277 were
      insufficient, and a triple alanine substitution within the EBNA3A core RBP-Jkappa
      binding domain was a null mutation. In reverse genetic experiments with IB4 LCLs,
      the effects of conditional EBNA3A overexpression on c-myc expression and
      proliferation did not require amino acids 524 to 944 but did require amino acids
      278 to 524 as well as wild-type sequence in the core RBP-Jkappa binding domain.
      The dependence of EBNA3A effects on the core RBP-Jkappa interaction domain and on
      the more C-terminal amino acids (amino acids 278 to 524) required for efficient
      RBP-Jkappa association strongly implicates RBP-Jkappa in c-myc promoter
      regulation.

PMID- 12502817
TI  - Actinomycin D induces high-level resistance to thymidine analogs in replication
      of human immunodeficiency virus type 1 by interfering with host cell thymidine
      kinase expression.
AB  - Actinomycin D (ActD) is a transcription inhibitor and has been used in the
      treatment of certain forms of cancer. ActD has been reported to be a potential
      inhibitor of human immunodeficiency virus type 1 (HIV-1) replication due to its
      ability to inhibit reverse transcription. In contrast to what was expected, low
      concentrations of ActD (1 to 10 nM) upregulated HIV-1 replication 8- to 10-fold
      in MT-2 cells and had no effect on HIV-2 replication or on HIV-1 replication in
      MT-4, Jurkat, or peripheral blood mononuclear cells. The upregulation of HIV-1
      replication was associated with an increase in HIV-1 transcription and a decrease
      in CD4 and CXCR4 expression. To further evaluate the effects of ActD on emergence
      of drug resistance in HIV-1 replication, a series of drug resistance assays were
      performed. Of interest, treatment of MT-2 cells with ActD also led to a high
      level of resistance to thymidine analogs (>1,000-fold increase in resistance to
      zidovudine and >250-fold to stavudine) but not to other nucleoside reverse
      transcriptases (RT), nonnucleoside RT, or protease inhibitors. This resistance
      appeared to be due to a suppression of host cell thymidine kinase-1 (TK-1)
      expression. These results indicate that ActD leads to a novel form of thymidine
      analog resistance by suppressing host cell TK-1 expression. These results suggest
      that administration of combination drugs to HIV-1-infected patients may induce
      resistance to antiretroviral compounds via a modification of cellular factors.

PMID- 12502818
TI  - Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1
      isolates of subtypes B and C.
AB  - Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion
      within the human population have led to unequal distribution of HIV-1 group M
      subtypes. In particular, recent outgrowth of subtype C in southern Africa, India,
      and China has fueled speculation that subtype C isolates may be more fit in vivo.
      In this study, nine subtype B and six subtype C HIV-1 isolates were added to
      peripheral blood mononuclear cell cultures for a complete pairwise competition
      experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P
      < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant.
      Increased fitness of subtype B over subtype C was also observed in primary CD4(+)
      T cells and macrophages from different human donors but not in skin-derived human
      Langerhans cells. Detailed analysis of the retroviral life cycle during several B
      and C virus competitions indicated that the efficiency of host cell entry may
      have a significant impact on relative fitness. Furthermore, phyletic analyses of
      fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate,
      higher fitness mapped to the subtype B env gene rather than the subtype C gag and
      pol genes. These results suggest that subtype B and C HIV-1 may be transmitted
      with equal efficiency (Langerhans cell data) but that subtype C isolates may be
      less fit following initial infection (T-cell and macrophage data) and may lead to
      slower disease progression.

PMID- 12502819
TI  - Subgroup B and F fiber chimeras eliminate normal adenovirus type 5 vector
      transduction in vitro and in vivo.
AB  - Altering adenovirus vector (Ad vector) targeting is an important goal for a
      variety of gene therapy applications and involves eliminating or reducing the
      normal tropism of a vector and retargeting through a distinct receptor-ligand
      pathway. The first step of Ad vector infection is high-affinity binding to a
      target cellular receptor. For the majority of adenoviruses and Ad vectors, the
      fiber capsid protein serves this purpose, binding to the coxsackievirus and
      adenovirus receptor (CAR) present on a variety of cell types. In this study we
      have explored a novel approach to altering Ad type 5 (Ad5) vector targeting based
      on serotypic differences in fiber function. The subgroup B viruses bind to an
      unidentified receptor that is distinct from CAR. The subgroup F viruses are the
      only adenoviruses that express two distinct terminal exons encoding fiber open
      reading frames. We have constructed chimeric fiber adenoviruses that utilize the
      tandem fiber arrangement of the subgroup F genome configuration. By taking
      advantage of serotypic differences in fiber expression, fiber shaft length, and
      fiber binding efficiency, we have developed a tandem fiber vector that has low
      binding efficiency for the known fiber binding sites, does not rely on an Ad5
      based fiber, and can be grown to high titer using conventional cell lines.
      Importantly, when characterizing these vectors in vivo, we find the subgroup B
      system and our optimal tandem fiber system demonstrate reduced liver transduction
      by over 2 logs compared to an Ad5 fiber vector. These attributes make the tandem
      fiber vector a useful alternative to conventional strategies for fiber
      manipulation of adenovirus vectors.

PMID- 12502820
TI  - Prevention of disease induced by a partially heterologous AIDS virus in rhesus
      monkeys by using an adjuvanted multicomponent protein vaccine.
AB  - Recombinant protein subunit AIDS vaccines have been based predominantly on the
      virus envelope protein. Such vaccines elicit neutralizing antibody responses that
      can provide type-specific sterilizing immunity, but in most cases do not confer
      protection against divergent viruses. In this report we demonstrate that a
      multiantigen subunit protein vaccine was able to prevent the development of
      disease induced in rhesus monkeys by a partially heterologous AIDS virus. The
      vaccine was composed of recombinant human immunodeficiency virus type 1 (HIV-1)
      gp120, NefTat fusion protein, and simian immunodeficiency virus (SIV) Nef
      formulated in the clinically tested adjuvant AS02A. Upon challenge of genetically
      unselected rhesus monkeys with the highly pathogenic and partially heterologous
      SIV/HIV strain SHIV(89.6p) the vaccine was able to reduce virus load and protect
      the animals from a decline in CD4-positive cells. Furthermore, vaccination
      prevented the development of AIDS for more than 2.5 years. The combination of the
      regulatory proteins Nef and Tat together with the structural protein gp120 was
      required for vaccine efficacy.

PMID- 12502821
TI  - Long-range effects of retroviral insertion on c-myb: overexpression may be
      obscured by silencing during tumor growth in vitro.
AB  - The c-myb oncogene is a frequent target for retroviral activation in hemopoietic
      tumors of avian and mammalian species. While insertions can target the gene
      directly, numerous clusters of retroviral insertion sites have been identified
      which map close to c-myb and outside the transcription unit in T-lymphomas (Ahi
      1, fit-1, and Mis-2) and monocytic and myeloid leukemias (Mml1, Mml2, Mml3, and
      Epi-1). Previous analyses showed no consistent effect of these insertions on c
      myb expression, raising the possibility that other nearby genes were the true
      targets. In contrast, our analysis of four cell lines established from lymphomas
      bearing insertions at fit-1 (fti-1) (feline leukemia virus) and Ahi-1 (Moloney
      murine leukemia virus) shows that these display higher expression levels of c-myb
      RNA and protein compared to a panel of phenotypically similar cell lines lacking
      such insertions. An interesting feature of the cell lines with long-range c-myb
      insertions was that each also carried an activated Myc allele. The potential for
      oncogenic synergy between Myb and Myc in T-cell lymphoma was confirmed in
      transgenic mice overexpressing alleles of both genes in the T-cell compartment,
      lending further credence to the case for c-myb as the major target for long-range
      activation. In contrast, mapping and analysis of c-myb neighboring genes (HBS1
      and FLJ20069) showed that the expression of these genes did not correlate well
      with the presence of proviral insertions. A possible explanation for the
      paradoxical behavior of c-myb was provided by one of the murine T-lymphoma lines
      bearing an insertion at Ahi-1 (p/m16i) that reproducibly down-regulated c-myb RNA
      and protein to very low levels or undetectable levels on prolonged culture. Our
      observations implicate c-myb as a key target of upstream and downstream
      retroviral insertions. However, overexpression may become dispensable during
      outgrowth in vitro, and perhaps during tumor progression in vivo, providing a
      potential rationale for the previously observed discordance between retroviral
      insertion and c-myb expression levels.

PMID- 12502822
TI  - Identification of protective epitopes on ebola virus glycoprotein at the single
      amino acid level by using recombinant vesicular stomatitis viruses.
AB  - Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no
      effective vaccines or antiviral compounds for this infectious disease. Passive
      transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus
      infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L.
      Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes
      responsible for neutralization have been only partially characterized because
      some of the MAbs do not recognize the short synthetic peptides used for epitope
      mapping. To identify the amino acids recognized by neutralizing and protective
      antibodies, we generated a recombinant vesicular stomatitis virus (VSV)
      containing the Ebola virus glycoprotein-encoding gene instead of the VSV G
      protein-encoding gene and used it to select escape variants by growing it in the
      presence of a MAb (133/3.16 or 226/8.1) that neutralizes the infectivity of the
      virus. All three variants selected by MAb 133/3.16 contained a single amino acid
      substitution at amino acid position 549 in the GP2 subunit. By contrast, MAb
      226/8.1 selected three different variants containing substitutions at positions
      134, 194, and 199 in the GP1 subunit, suggesting that this antibody recognized a
      conformational epitope. Passive transfer of each of these MAbs completely
      protected mice from a lethal Ebola virus infection. These data indicate that
      neutralizing antibody cocktails for passive prophylaxis and therapy of Ebola
      hemorrhagic fever can reduce the possibility of the emergence of antigenic
      variants in infected individuals.

PMID- 12502823
TI  - Initiation of poliovirus negative-strand RNA synthesis requires precursor forms
      of p2 proteins.
AB  - The replication proteins encoded in the P2 region of the poliovirus genome induce
      extensive rearrangement of cellular membranes into vesicles and are a required
      component of viral RNA replication complexes. To identify distinct viral
      protein(s) from the P2 region of the genome that were required to form functional
      RNA replication complexes, the P2 proteins were expressed in addition to P3 in
      HeLa S10 translation-RNA replication reactions. Membrane-associated preinitiation
      replication complexes were isolated from these reactions and used to measure
      negative-strand synthesis. The formation of replication complexes capable of
      initiating negative-strand synthesis was observed when either P23 or when P2 and
      P3 were expressed in the HeLa S10 translation-replication reactions. The amount
      of negative-strand RNA synthesized with P2 and P3 was approximately 50% of that
      observed with P23. Negative-strand synthesis was not observed when the processed
      forms of the P2 proteins (e.g., 2A, 2B, 2C, 2AB, and 2BC) were used in various
      combinations in place of P2. In contrast, the expression of 2A and 2BCP3
      supported negative-strand synthesis at the same level observed with P23.
      Therefore, functional replication complexes were formed in reaction mixtures that
      contained either 2A and 2BCP3 or P2 and P3. Genetic complementation analysis of
      P23 RNA that contained a lethal mutation in 2C confirmed these results. The
      expression of 2BCP3 in trans restored the replication of P23-2C(P131N) RNA to
      wild-type levels. The expression of P2 and P3 also complemented the replication
      of this mutant RNA, although very inefficiently. Complementation was not observed
      in reactions that contained P2 alone, 2BC, or 2C. Based on these results, we
      propose that RNA replication complexes are initially formed with the primary
      cleavage products of P23 (i.e., P2 and P3 or 2A and 2BCP3), and that 2A and 2BCP3
      are preferentially used in this process.

PMID- 12502824
TI  - Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human
      immunodeficiency virus type 1 do not interfere with the activity of a
      neutralizing antibody against the same site.
AB  - We have investigated whether nonneutralizing monoclonal antibodies (MAbs) to the
      gp120 subunit of the envelope glycoprotein (Env) complex of human
      immunodeficiency virus type 1 (HIV-1) can interfere with HIV-1 neutralization by
      another anti-gp120 MAb. We used neutralizing (b12) and nonneutralizing (205-42
      15, 204-43-1, 205-46-9) MAbs to the epitope cluster overlapping the CD4-binding
      site (CD4BS) on gp120. All the MAbs, neutralizing or otherwise, cross-competed
      for binding to monomeric gp120, indicating the close topological proximity of
      their epitopes. However, the nonneutralizing CD4BS MAbs did not interfere with
      the neutralization activity of MAb b12. In contrast, in a binding assay using
      oligomeric Env expressed on the surface of Env-transfected cells, the
      nonneutralizing MAbs did partially compete with b12 for Env binding. The surface
      of Env-transfected cells contains two categories of binding site for CD4BS MAbs.
      One type of site is recognized by both b12 and nonneutralizing CD4BS MAbs; the
      other is recognized by only b12. Binding assays for Env-gp120 interactions based
      on the use of monomeric gp120 or Env-transfected cells do not predict the outcome
      of HIV-1 neutralization assays, and they should therefore be used only with
      caution when gauging the properties of anti-Env MAbs.

PMID- 12502825
TI  - Antiviral effect and virus-host interactions in response to alpha interferon,
      gamma interferon, poly(i)-poly(c), tumor necrosis factor alpha, and ribavirin in
      hepatitis C virus subgenomic replicons.
AB  - The recently developed hepatitis C virus (HCV) subgenomic replicon system was
      utilized to evaluate the efficacy of several known antiviral agents. Cell lines
      that persistently maintained a genotype 1b replicon were selected. The replicon
      resident in each cell line had acquired adaptive mutations in the NS5A region
      that increased colony-forming efficiency, and some replicons had acquired NS3
      mutations that alone did not enhance colony-forming efficiency but were
      synergistic with NS5A mutations. A replicon constructed from the infectious clone
      of the HCV-1 strain (genotype 1a) was not capable of inducing colony formation
      even after the introduction of adaptive mutations identified in the genotype 1b
      replicon. Alpha interferon (IFN-alpha), IFN-gamma, and ribavirin exhibited
      antiviral activity, while double-stranded RNA (dsRNA) and tumor necrosis factor
      alpha did not. Analysis of transcript levels for a series of genes stimulated by
      IFN (ISGs) or dsRNA following treatment with IFN-alpha, IFN-gamma, and dsRNA
      revealed that both IFNs increased ISG transcript levels, but that some aspect of
      the dsRNA response pathway was defective in Huh7 cells and replicon cell lines in
      comparison to primary chimpanzee and tamarin hepatocytes. The colony-forming
      efficiency of the replicon was reduced or eliminated following replication in the
      presence of ribavirin, implicating the induction of error-prone replication. The
      potential role of error-prone replication in the synergy observed between IFN
      alpha and ribavirin in attaining sustained viral clearance is discussed. These
      studies reveal characteristics of Huh7 cells that may contribute to their unique
      capacity to support HCV RNA synthesis and demonstrate the utility of the replicon
      system for mechanistic studies on antiviral agents.

PMID- 12502826
TI  - Identification and characterization of avian retroviruses in chicken embryo
      derived yellow fever vaccines: investigation of transmission to vaccine
      recipients.
AB  - All currently licensed yellow fever (YF) vaccines are propagated in chicken
      embryos. Recent studies of chick cell-derived measles and mumps vaccines show
      evidence of two types of retrovirus particles, the endogenous avian retrovirus
      (EAV) and the endogenous avian leukosis virus (ALV-E), which originate from the
      chicken embryonic fibroblast substrates. In this study, we investigated substrate
      derived avian retrovirus contamination in YF vaccines currently produced by three
      manufacturers (YF-vax [Connaught Laboratories], Stamaril [Aventis], and YF
      FIOCRUZ [FIOCRUZ-Bio-Manguinhos]). Testing for reverse transcriptase (RT)
      activity was not possible because of assay inhibition. However, Western blot
      analysis of virus pellets with anti-ALV RT antiserum detected three distinct RT
      proteins in all vaccines, indicating that more than one source is responsible for
      the RTs present in the vaccines. PCR analysis of both chicken substrate DNA and
      particle-associated RNA from the YF vaccines showed no evidence of the long
      terminal repeat sequences of exogenous ALV subgroups A to D in any of the
      vaccines. In contrast, both ALV-E and EAV particle-associated RNA were detected
      at equivalent titers in each vaccine by RT-PCR. Quantitative real-time RT-PCR
      revealed 61,600, 348,000, and 1,665,000 ALV-E RNA copies per dose of Stamaril, YF
      FIOCRUZ, and YF-vax vaccines, respectively. ev locus-specific PCR testing of the
      vaccine-associated chicken substrate DNA was positive both for the nondefective
      ev-12 locus in two vaccines and for the defective ev-1 locus in all three
      vaccines. Both intact and ev-1 pol sequences were also identified in the particle
      associated RNA. To investigate the risks of transmission, serum samples from 43
      YF vaccine recipients were studied. None of the samples were seropositive by an
      ALV-E-based Western blot assay or had detectable EAV or ALV-E RNA sequences by RT
      PCR. YF vaccines produced by the three manufacturers all have particles
      containing EAV genomes and various levels of defective or nondefective ALV-E
      sequences. The absence of evidence of infection with ALV-E or EAV in 43 YF
      vaccine recipients suggests low risks for transmission of these viruses, further
      supporting the safety of these vaccines.

PMID- 12502827
TI  - The adenovirus e3 promoter is sensitive to activation signals in human T cells.
AB  - The group C adenoviruses typically cause acute respiratory disease in young
      children. In addition, a persistent phase of infection has been observed in which
      virus may be shed for years without producing overt pathology. Our laboratory
      recently reported that group C adenovirus DNA can be found in tonsil and adenoid
      T lymphocytes from the majority of pediatric donors (C. T. Garnett, D. Erdman, W.
      Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). This finding suggests
      that immune evasion strategies of human adenoviruses may be directed, in part,
      toward protection of persistently or latently infected T lymphocytes. Many of the
      adenoviral gene products implicated in prevention of immune destruction of virus
      infected cells are encoded within the E3 transcription unit. In this study, the
      E3 promoter was evaluated for sensitivity to T-cell activation signals by using a
      promoter reporter plasmid. Indeed, this promoter is extremely sensitive to T-cell
      activation, with phorbol myristate acetate (PMA) plus ionomycin increasing E3
      directed transcription 100-fold. By comparison, in the same cells E1A expression
      leads to a 5.5-fold increase in transcription from the E3 promoter. In contrast
      to induction by E1A, activation by PMA plus ionomycin requires the two E3 NF
      kappaB binding sites. Interestingly, expression of E1A inhibits induction of the
      E3 promoter in response to T-cell activation while increasing E3 promoter
      activity in unactivated cells. Collectively, these data suggest that the E3
      promoter may have evolved the capacity to respond to T-cell activation in the
      absence of E1A expression and may act to upregulate antiapoptotic gene expression
      in order to promote survival of persistently infected T lymphocytes.

PMID- 12502828
TI  - Reversion of the M184V mutation in simian immunodeficiency virus reverse
      transcriptase is selected by tenofovir, even in the presence of lamivudine.
AB  - The methionine-to-valine mutation in codon 184 (M184V) in reverse transcriptase
      (RT) of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency
      virus (SIV) confers resistance to (-)-2'-deoxy-3'-thiacytidine (3TC; lamivudine)
      and increased sensitivity to 9-[2-(phosphonomethoxy)propyl]adenine (PMPA;
      tenofovir). We have used the SIV model to evaluate the effect of the M184V
      mutation on the emergence of resistance to the combination of 3TC plus PMPA. A
      site-directed mutant of SIVmac239 containing M184V (SIVmac239-184V) was used to
      select for resistance to both 3TC and PMPA by serial passage in the presence of
      increasing concentrations of both drugs. Under these selection conditions, the
      M184V mutation reverted in the majority of the selections. Variants resistant to
      both drugs were found to have the lysine-to-arginine mutation at codon 65 (K65R),
      which has previously been associated with resistance to PMPA in both SIV and HIV.
      Similarly, in rhesus macaques infected with SIVmac239-184V for 46 weeks and
      treated daily with (-)-2'-deoxy-5-fluoro-3'-thiacytidine [(-)-FTC], there was no
      reversion of M184V, but this mutation reverted to 184 M in all three animals
      within 24 weeks of treatment with (-)-FTC and PMPA. Although the addition of PMPA
      to the (-)-FTC therapy induced a decrease in virus loads in plasma, these loads
      eventually returned to pre-PMPA levels in each case. All animals receiving this
      combination developed the K65R mutation. These results demonstrate that the
      combination of PMPA with 3TC or (-)-FTC selects for the K65R mutation and against
      the M184V mutation in SIV RT.

PMID- 12502829
TI  - Human immunodeficiency virus type 1 Vif is efficiently packaged into virions
      during productive but not chronic infection.
AB  - Packaging of the human immunodeficiency virus type 1 Vif protein into virus
      particles is mediated through an interaction with viral genomic RNA and results
      in the association of Vif with the nucleoprotein complex. Despite the specificity
      of this process, calculations of the amount of Vif packaged have produced vastly
      different results. Here, we compared the efficiency of packaging of Vif into
      virions derived from acutely and chronically infected H9 cells. We found that Vif
      was efficiently packaged into virions from acutely infected cells (60 to 100
      copies per virion), while packaging into virions from chronically infected H9
      cells was near the limit of detection (four to six copies of Vif per virion).
      Superinfection by an exogenous Vif-defective virus did not rescue packaging of
      endogenous Vif expressed in the chronically infected culture. In contrast,
      exogenous Vif expressed by superinfection of wild-type virus was readily packaged
      (30 to 40 copies per virion). Biochemical analyses suggest that the differences
      in the relative packaging efficiencies were not due to gross differences in the
      steady-state distribution of Vif in chronically or acutely infected cells but are
      likely due to differences in the relative rates of de novo synthesis of Vif.
      Despite its low packaging efficiency, endogenously expressed Vif was sufficient
      to direct the production of viruses with almost wild-type infectivity. The
      results from our study provide novel insights into the biochemical properties of
      Vif and offer an explanation for the reported differences regarding Vif
      packaging.

PMID- 12502830
TI  - Determinants of the host range restriction of replication of bovine parainfluenza
      virus type 3 in rhesus monkeys are polygenic.
AB  - The Kansas strain of bovine parainfluenza virus type 3 (BPIV3) is 100- to 1,000
      fold restricted in replication in the respiratory tracts of nonhuman primates
      compared to human PIV3 (HPIV3), an important pathogen of infants and young
      children. BPIV3 is also restricted in replication in human infants and children,
      yet it is immunogenic and is currently being evaluated in clinical trials as a
      vaccine candidate to protect against illness caused by HPIV3. We have examined
      the genetic basis for the host range attenuation phenotype of BPIV3 by exchanging
      each open reading frame (ORF) of a recombinant wild-type HPIV3 with the analogous
      ORF from BPIV3, with the caveats that the multiple ORFs of the P gene were
      exchanged as a single unit and that the HN and F genes were exchanged as a single
      unit. Recombinant chimeric bovine-human PIV3s were recovered from cDNA, and the
      levels of viral replication in vitro and in the respiratory tract of rhesus
      monkeys were determined. Recombinant chimeric HPIV3s bearing the BPIV3 N or P ORF
      were highly attenuated in the upper and lower respiratory tracts of monkeys,
      whereas those bearing the BPIV3 M or L ORF or the F and HN genes were only
      moderately attenuated. This indicates that the genetic determinants of the host
      range restriction of replication of BPIV3 for primates are polygenic, with the
      major determinants being the N and P ORFs. Monkeys immunized with these bovine
      human chimeric viruses, including the more highly attenuated ones, developed
      higher levels of HPIV3 hemagglutination-inhibiting serum antibodies than did
      monkeys immunized with BPIV3 and were protected from challenge with wild-type
      HPIV3. Furthermore, host range determinants could be combined with attenuating
      point mutations to achieve an increased level of attenuation. Thus, chimeric
      recombinant bovine-human PIV3 viruses that manifest different levels of
      attenuation in rhesus monkeys are available for evaluation as vaccine candidates
      to protect infants from the severe lower respiratory tract disease caused by
      HPIV3.

PMID- 12502831
TI  - An attenuating mutation in nsP1 of the Sindbis-group virus S.A.AR86 accelerates
      nonstructural protein processing and up-regulates viral 26S RNA synthesis.
AB  - The Sindbis-group alphavirus S.A.AR86 encodes a threonine at nonstructural
      protein 1 (nsP1) 538 that is associated with neurovirulence in adult mice.
      Mutation of the nsP1 538 Thr to the consensus Ile found in nonneurovirulent
      Sindbis-group alphaviruses attenuates S.A.AR86 for adult mouse neurovirulence,
      while introduction of Thr at position 538 in a nonneurovirulent Sindbis virus
      background confers increased neurovirulence (M. T. Heise et al., J. Virol.
      74:4207-4213, 2000). Since changes in the viral nonstructural region are likely
      to affect viral replication, studies were performed to evaluate the effect of Thr
      or Ile at nsP1 538 on viral growth, nonstructural protein processing, and RNA
      synthesis. Multistep growth curves in Neuro2A and BHK-21 cells revealed that the
      attenuated s51 (nsP1 538 Ile) virus had a slight, but reproducible growth
      advantage over the wild-type s55 (nsP1 538 Thr) virus. nsP1 538 lies within the
      cleavage recognition domain between nsP1 and nsP2, and the presence of the
      attenuating Ile at nsP1 538 accelerated the processing of S.A.AR86 nonstructural
      proteins both in vitro and in infected cells. Since nonstructural protein
      processing is known to regulate alphavirus RNA synthesis, experiments were
      performed to evaluate the effect of Ile or Thr at nsP1 538 on viral RNA
      synthesis. A combination of S.A.AR86-derived reporter assays and RNase protection
      assays determined that the presence of Ile at nsP1 538 led to earlier expression
      from the viral 26S promoter without affecting viral minus- or plus-strand
      synthesis. These results suggest that slower nonstructural protein processing and
      delayed 26S RNA synthesis in wild-type S.A.AR86 infections may contribute to the
      adult mouse neurovirulence phenotype of S.A.AR86.

PMID- 12502832
TI  - There are two different species B adenovirus receptors: sBAR, common to species
      B1 and B2 adenoviruses, and sB2AR, exclusively used by species B2 adenoviruses.
AB  - Unlike most adenovirus (Ad) serotypes, the species B Ads do not use the coxsackie
      adenovirus receptor as an attachment receptor. The species B attachment
      receptor(s) has not yet been identified and is also poorly characterized. Species
      B Ads can be further divided into species B1 and B2 Ads, and these display
      different organ tropisms, suggesting a difference in receptor usage. We have
      studied the receptor interactions of the species B1 serotypes 3p and 7p and the
      species B2 serotypes 11p and 35 and characterized the properties of the species B
      receptor(s). Reciprocal blocking experiments using unlabeled Ad11p or Ad3p
      virions to block the binding to A549 cells of (35)S-labeled 3p, 7p, 11p, and 35
      showed that only Ad11p virions efficiently blocked the binding of all the species
      B Ads studied (> or =70%). Thus, there is apparently a common species B Ad
      receptor (sBAR). However, Ad3p virions only partially (< or =30%) blocked the
      binding of Ad11p and Ad35 to A549 cells. Binding experiments after trypsin
      treatment of the cells confirmed that the species B2 serotypes address at least
      two different receptors on A549 and J82 cells, since sBAR is trypsin sensitive
      but the species B2 Ad receptor (sB2AR) is not. Both receptors are proteins or
      glycoproteins, since binding of all species B serotypes was abolished after
      proteinase K or subtilisin treatment of A549 or J82 cells. Furthermore, binding
      of the species B serotypes to sBAR was abolished with EDTA and restored with
      Ca(2+), whereas the binding of Ad11p and Ad35 to SB2AR was independent of
      divalent cations.

PMID- 12502833
TI  - Control of viremia and prevention of simian-human immunodeficiency virus-induced
      disease in rhesus macaques immunized with recombinant vaccinia viruses plus
      inactivated simian immunodeficiency virus and human immunodeficiency virus type 1
      particles.
AB  - An effective vaccine against the human immunodeficiency virus type 1 (HIV-1) will
      very likely have to elicit both cellular and humoral immune responses to control
      HIV-1 strains of diverse geographic and genetic origins. We have utilized a
      pathogenic chimeric simian-human immunodeficiency virus (SHIV) rhesus macaque
      animal model system to evaluate the protective efficacy of a vaccine regimen that
      uses recombinant vaccinia viruses expressing simian immunodeficiency virus (SIV)
      and HIV-1 structural proteins in combination with intact inactivated SIV and HIV
      1 particles. Following virus challenge, control animals experienced a rapid and
      complete loss of CD4(+) T cells, sustained high viral loads, and developed
      clinical disease by 17 to 21 weeks. Although all of the vaccinated monkeys became
      infected, they displayed reduced postpeak viremia, had no significant loss of
      CD4(+) T cells, and have remained healthy for more than 15 months postinfection.
      CD8(+) T-cell and neutralizing antibody responses in vaccinated animals following
      challenge were demonstrable. Despite the control of disease, virus was readily
      isolated from the circulating peripheral blood mononuclear cells of all vaccinees
      at 22 weeks postchallenge, indicating that immunologic control was incomplete.
      Virus recovered from the animal with the lowest postchallenge viremia generated
      high virus loads and an irreversible loss of CD4(+) T-cell loss following its
      inoculation into a naive animal. These results indicate that despite the
      protection from SHIV-induced disease, the vaccinated animals still harbored
      replication-competent and pathogenic virus.

PMID- 12502834
TI  - The stability of the duplex between sense and antisense transcription-regulating
      sequences is a crucial factor in arterivirus subgenomic mRNA synthesis.
AB  - Subgenomic mRNAs of nidoviruses (arteriviruses and coronaviruses) are composed of
      a common leader sequence and a "body" part of variable size, which are derived
      from the 5'- and 3'-proximal part of the genome, respectively. Leader-to-body
      joining has been proposed to occur during minus-strand RNA synthesis and to
      involve transfer of the nascent RNA strand from one site in the template to
      another. This discontinuous step in subgenomic RNA synthesis is guided by short
      transcription-regulating sequences (TRSs) that are present at both these template
      sites (leader TRS and body TRS). Sense-antisense base pairing between the leader
      TRS in the plus strand and the body TRS complement in the minus strand is crucial
      for strand transfer. Here we show that extending the leader TRS-body TRS duplex
      beyond its wild-type length dramatically enhanced the subgenomic mRNA synthesis
      of the arterivirus Equine arteritis virus (EAV). Generally, the relative amount
      of a subgenomic mRNA correlated with the calculated stability of the
      corresponding leader TRS-body TRS duplex. In addition, various leader TRS
      mutations induced the generation of minor subgenomic RNA species that were not
      detected upon infection with wild-type EAV. The synthesis of these RNA species
      involved leader-body junction events at sites that bear only limited resemblance
      to the canonical TRS. However, with the mutant leader TRS, but not with the wild
      type leader TRS, these sequences could form a duplex that was stable enough to
      direct subgenomic RNA synthesis, again demonstrating that the stability of the
      leader TRS-body TRS duplex is a crucial factor in arterivirus subgenomic mRNA
      synthesis.

PMID- 12502835
TI  - Characterization of the genomic promoter of the prototypic arenavirus lymphocytic
      choriomeningitis virus.
AB  - The genome of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV)
      consists of two negative-sense, single-strand RNA segments designated L and S.
      Arenavirus genomes exhibit high sequence conservation at their 3' ends. All
      arenavirus genomes examined to date have a conserved terminal sequence element
      (3'-terminal 20 nucleotides [nt]) thought to be a highly conserved viral
      promoter. Terminal complementarity between the 5' and 3' ends of the L and S RNAs
      predicts the formation of a thermodynamically stable panhandle structure that
      could contribute to the control of RNA synthesis. We investigated these issues by
      using a transcription- and replication-competent minireplicon system. A series of
      overlapping deletions spanning the 3'-terminal 20-nt region of an LCMV minigenome
      (MG) was generated, and the mutant MGs were analyzed for their activity as
      templates for RNA synthesis by the LCMV polymerase. The minimal LCMV genomic
      promoter was found to be contained within the 3'-terminal 19 nt. Substitution of
      C for G at the last 3'-end nucleotide position in the MG resulted in nondetection
      of RNA transcription or replication, whereas the addition of a C at the 3' end
      did not have any significant affect on RNA synthesis mediated by the LCMV
      polymerase. All other mutations introduced within the 3'-terminal 19 nt of the MG
      resulted in undetectable levels of promoter activity. Deletions and nucleotide
      substitutions within the MG 5' end that disrupted terminal complementarity
      abolished chloramphenicol acetyltransferase expression and RNA synthesis mediated
      by the LCMV polymerase. These findings indicate that both sequence specificity
      within the 3'-terminal 19 nt and the integrity of the predicted panhandle
      structure appear to be required for efficient RNA synthesis mediated by the LCMV
      polymerase.

PMID- 12502836
TI  - Two distinct mechanisms ensure transcriptional polarity in double-stranded RNA
      bacteriophages.
AB  - In most double-stranded RNA (dsRNA) viruses, RNA transcription occurs inside a
      polymerase (Pol) complex particle, which contains an RNA-dependent RNA Pol
      subunit as a minor component. Only plus- but not minus-sense copies of genomic
      segments are produced during this reaction. In the case of phi6, a dsRNA
      bacteriophage from the Cystoviridae family, isolated Pol synthesizes
      predominantly plus strands using virus-specific dsRNAs in vitro, thus suggesting
      that Pol template preferences determine the transcriptional polarity. Here, we
      dissect transcription reactions catalyzed by Pol complexes and Pol subunits of
      two other cystoviruses, phi8 and phi13. While both Pol complexes synthesize
      exclusively plus strands over a wide range of conditions, isolated Pol subunits
      can be stimulated by Mn(2+) to produce minus-sense copies on phi13 dsRNA
      templates. Importantly, all three Pol subunits become more prone to the native
      like plus-strand synthesis when the dsRNA templates (including phi13 dsRNA) are
      activated by denaturation before the reaction. Based on these and earlier
      observations, we propose a model of transcriptional polarity in Cystoviridae
      controlled on two independent levels: Pol affinity to plus-strand initiation
      sites and accessibility of these sites to the Pol in a single-stranded form.

PMID- 12502837
TI  - Glycosaminoglycan binding properties of natural venezuelan equine encephalitis
      virus isolates.
AB  - Equine-virulent, epidemic/epizootic strains of Venezuelan equine encephalitis
      (VEE) virus (VEEV) arise via mutation of progenitor enzootic strains that
      replicate poorly in equines. Sequencing studies have implicated positively
      charged amino acids on the surface of the E2 envelope glycoprotein in the
      acquisition of equine virulence and viremia potential, suggesting that changes in
      binding to cell surface glycosaminoglycans (GAGs) may mediate VEE emergence.
      Therefore, we evaluated the binding of natural enzootic and epizootic VEEV
      isolates to Chinese hamster ovary (CHO) cells expressing normal, high levels of
      GAGs as well as to mutant CHO cells lacking GAG expression. Binding to GAGs was
      not consistently associated with the epizootic phenotype, and cell culture
      passages resulted in increased GAG binding. The low levels of GAG binding
      exhibited by some low-passage, equine-virulent subtype IC VEEV strains indicate
      that the positive-charge E2 mutations implicated in VEE subtype IC emergence are
      not artifacts of laboratory passage and suggest that GAG binding does not play a
      major role in mediating VEE emergence. The increased GAG binding exhibited by
      VEEV strain CPA201 from the 1993 Mexican epizootic, when compared to that of
      closely related enzootic subtype IE strains, was shown to result from a Glu-to
      Lys mutation at position 117 of the E2 envelope glycoprotein.

PMID- 12502838
TI  - Varicella-zoster virus open reading frame 21, which is expressed during latency,
      is essential for virus replication but dispensable for establishment of latency.
AB  - Varicella-zoster virus (VZV) open reading frame 21 (ORF21) is one of at least
      five VZV genes expressed in latently infected human and rodent ganglia. To
      determine whether ORF21 is required for latent and lytic infection, we deleted
      99% of ORF21 from the viral genome. The ORF21 deletion mutant virus could be
      propagated only in a cell line expressing the ORF21 protein. Insertion of the
      herpes simplex virus type 1 (HSV-1) homolog of VZV ORF21, HSV-1 UL37, into the
      ORF21 deletion mutant failed to complement the mutant for growth in cell culture.
      Inoculation of cotton rats with the ORF21 deletion virus resulted in latent
      infection in numbers of animals similar to those infected after inoculation with
      the parental virus. The mean numbers of latent VZV genomes were similar in
      animals infected with parental and ORF21 deletion viruses. Transcription of
      ORF63, another latency-associated gene, was detected in ganglia from similar
      numbers of animals infected with the mutant and parental viruses. Thus, ORF21 is
      the first VZV gene expressed during latency that has been shown to be dispensable
      for the establishment of latent infection.

PMID- 12502839
TI  - Evidence of the coevolution of antigenicity and host cell tropism of foot-and
      mouth disease virus in vivo.
AB  - In this work we analyze the antigenic properties and the stability in cell
      culture of virus mutants recovered upon challenge of peptide-vaccinated cattle
      with foot-and-mouth disease virus (FMDV) C3 Arg85. Previously, we showed that a
      significant proportion of 29 lesions analyzed (41%) contained viruses with single
      amino acid replacements (R141G, L144P, or L147P) within a major antigenic site
      located at the G-H loop of VP1, known to participate also in interactions with
      integrin receptors. Here we document that no replacements at this site were found
      in viruses from 12 lesions developed in six control animals upon challenge with
      FMDV C3 Arg85. Sera from unprotected, vaccinated animals exhibited poor
      neutralization titers against mutants recovered from them. Sequence analyses of
      the viruses recovered upon 10 serial passages in BHK-21 and FBK-2 cells in the
      presence of preimmune (nonneutralizing) sera revealed that mutants reverted to
      the parental sequence, suggesting an effect of the amino acid replacements in the
      interaction of the viruses with cells. Parallel passages in the presence of
      subneutralizing concentrations of immune homologous sera resulted in the
      maintenance of mutations R141G and L147P, while mutation L144P reverted to the C3
      Arg85 sequence. Reactivity with a panel of FMDV type C-specific monoclonal
      antibodies indicated that mutant viruses showed altered antigenicity. These
      results suggest that the selective pressure exerted by host humoral immune
      response can play a role in both the selection and stability of antigenic FMDV
      variants and that such variants can manifest alterations in cell tropism.

PMID- 12502840
TI  - Searching for interferon-induced genes that inhibit hepatitis B virus replication
      in transgenic mouse hepatocytes.
AB  - We have previously shown that alpha/beta interferon (IFN-alpha/beta) and IFN
      gamma inhibit hepatitis B virus (HBV) replication noncytopathically in the livers
      of HBV transgenic mice and in hepatocyte cell lines derived from these mice. The
      present study was designed to identify transcriptionally controlled
      hepatocellular genes that are tightly associated with the inhibition of HBV
      replication and that might, therefore, mediate the antiviral effect of these
      cytokines. Twenty-nine genes were identified, many of which have known or
      potential antiviral activity. Notably, multiple components of the
      immunoproteasome and ubiquitin-like proteins were strongly induced by both IFN
      alpha/beta and IFN-gamma, as were a number of GTP-binding proteins, including
      GTPases with known antiviral activity, chemokines, signaling molecules, and
      miscellaneous genes associated with antigen processing, DNA-binding, or
      cochaperone activity and several expressed sequence tags. The results suggest
      that one or more members of this relatively small subset of genes may mediate the
      antiviral effect of IFN-alpha/beta and IFN-gamma against HBV. We have already
      exploited this information by demonstrating that the antiviral activity of IFN
      alpha/beta and IFN-gamma is proteasome dependent.

PMID- 12502841
TI  - Altered pathogenesis of severe pneumovirus infection in response to combined
      antiviral and specific immunomodulatory agents.
AB  - We report here the responses of mice with symptomatic pneumovirus infection to
      combined antiviral and specific immunomodulatory agents. Mice infected with
      pneumonia virus of mice, a natural mouse pathogen that replicates the signs and
      symptoms of severe infection with respiratory syncytial virus (RSV), responded to
      the antiviral agent ribavirin when it was administered in the setting of
      endogenous (gene deletion) or exogenous (antibody-mediated) blockade of the MIP
      1alpha proinflammatory signaling cascade. Although neither treatment is effective
      alone, together they offer a dramatic reduction in symptoms and pathology, the
      most impressive of which is a significant reduction in morbidity and mortality.
      The findings presented are consistent with the notion of unique and independent
      contributions of virus replication and ongoing inflammation to the pathogenesis
      of severe respiratory virus infection, and they provide the impetus for the study
      of this treatment regimen in RSV-infected humans.

PMID- 12502842
TI  - A truncated form of Nef selected during pathogenic reversion of simian
      immunodeficiency virus SIVmac239Deltanef increases viral replication.
AB  - The live, attenuated vaccine simian immunodeficiency virus SIVmac239Deltanef
      efficiently protects rhesus macaques against infection with wild-type SIVmac but
      occasionally causes CD4(+) T-cell depletion and progression to simian AIDS
      (SAIDS). Virus recovered from a vaccinated macaque (Rh1490) that progressed to
      SAIDS had acquired an additional deletion in the nef gene, resulting in a
      frameshift that restored the original nef open reading frame (R. I. Connor, D. C.
      Montefiori, J. M. Binley, J. P. Moore, S. Bonhoeffer, A. Gettie, E. A. Fenamore,
      K. E. Sheridan, D. D. Ho, P. J. Dailey, and P. A. Marx, J. Virol. 72:7501-7509,
      1998). Intravenous inoculation of the Rh1490 viral isolate into four naive rhesus
      macaques induced CD4(+) T-cell depletion and disease in three out of four animals
      within 2 years, indicating a restoration of virulence. A DNA fragment
      encompassing the truncated nef gene amplified from the Rh1490 isolate was
      inserted into the genetic backbone of SIVmac239. The resulting clone, SIVmac239
      Delta2nef, expressed a Nef protein of approximately 23 kDa, while the original
      SIVmac239Deltanef clone expressed a shorter protein of 8 kDa. The revertant form
      of Nef did not cause downregulation of CD4, CD3, or major histocompatibility
      complex class I. The infectivity of SIVmac239-Delta2nef was similar to that of
      SIVmac239Deltanef in single-cycle assays using indicator cell lines. In contrast,
      SIVmac239-Delta2nef replicated more efficiently than SIVmac239Deltanef in
      peripheral blood mononuclear cell (PBMC) cultures infected under unstimulated
      conditions. The p27 Gag antigen levels in SIVmac239-Delta2nef-infected cultures
      were still lower than those obtained with wild-type SIVmac239, consistent with a
      partial recovery of Nef function. The transcriptional activity of long terminal
      repeat (LTR)-luciferase constructs containing the nef deletions did not differ
      markedly from that of wild-type LTR. Introduction of a premature stop codon
      within Nef-Delta2 abolished the replicative advantage in PBMCs, demonstrating
      that the Nef-Delta2 protein, rather than the structure of the U3 region of the
      LTR, was responsible for the increase in viral replication. Taken together, these
      results show that SIV with a deletion in the nef gene can revert to virulence and
      that expression of a form of nef with multiple deletions may contribute to this
      process by increasing viral replication.

PMID- 12502843
TI  - Negative regulation of mitotic promoting factor by the checkpoint kinase chk1 in
      simian virus 40 lytic infection.
AB  - Lytic infection of African green monkey kidney (CV-1) cells by simian virus 40
      (SV40) is characterized by stimulation of DNA synthesis leading to bypass of
      mitosis and replication of cellular and viral DNA beyond a 4C DNA content. To
      define mechanisms underlying the absence of mitosis, the expression levels of
      upstream regulatory molecules of mitosis-promoting factor (MPF) were compared in
      parallel synchronized cultures of SV40-infected and uninfected CV-1 cells. The
      DNA replication/damage checkpoint kinase Chk1 was phosphorylated in both
      uninfected and SV40-infected cultures arrested at G(1)/S by mimosine, consistent
      with checkpoint activation. Following release of uninfected cultures from G(1)/S,
      Chk1 phosphorylation was lost even though Chk1 protein levels were retained. In
      contrast, G(1)/S-released SV40-infected cultures exhibited dephosphorylation of
      Chk1 in S phase, followed by an increase in Chk1 phosphorylation coinciding with
      entry of infected cells into >G(2). Inhibitors of Chk1, UCN-01 and caffeine,
      induced mitosis and abnormal nuclear condensation and increased the protein
      kinase activity of MPF in SV40-infected CV-1 cells. These results demonstrate
      that SV40 lytic infection triggers components of a DNA damage checkpoint pathway.
      In addition, chemical inhibition of Chk1 activity suggests that Chk1 contributes
      to the absence of mitosis during SV40 lytic infection.

PMID- 12502844
TI  - Microarray analysis of host cell gene transcription in response to varicella
      zoster virus infection of human T cells and fibroblasts in vitro and SCIDhu skin
      xenografts in vivo.
AB  - During primary infection, varicella-zoster virus (VZV) is spread via lymphocytes
      to skin, where it induces a rash and establishes latency in sensory ganglia. A
      live, attenuated varicella vaccine (vOka) was generated by using the VZV Oka
      strain (pOka), but the molecular basis for vOka attenuation remains unknown.
      Little is known concerning the effects of wild-type or attenuated VZV on cellular
      gene regulation in the host cells that are critical for pathogenesis. In this
      study, transcriptional profiles of primary human T cells and fibroblasts infected
      with VZV in cell culture were determined by using 40,000-spot human cDNA
      microarrays. Cellular gene transcription in human skin xenografts in SCID mice
      that were infected with VZV in vivo was also evaluated. The profiles of cellular
      gene transcripts that were induced or inhibited in infected human foreskin
      fibroblasts (HFFs), T cells, and skin in response to pOka and vOka infection were
      similar. However, significant alterations in cellular gene regulation were
      observed among the three differentiated human cell types that were examined,
      suggesting specific differences in the biological consequences of VZV infection
      related to the target cell. Changes in cellular gene transcription detected by
      microarray analysis were confirmed for selected genes by quantitative real-time
      reverse transcription-PCR analysis of VZV-infected cells. Interestingly, the
      transcription of caspase 8 was found to be decreased in infected T cells but not
      in HFFs or skin, which may signify a tissue-specific antiapoptosis mechanism. The
      use of microarrays to demonstrate differences in effects on host cell genes in
      primary, biologically relevant cell types provides background information for
      experiments to link these various response phenotypes with mechanisms of VZV
      pathogenesis that are important for the natural course of human infection.

PMID- 12502845
TI  - Cytoplasmic tail of Moloney murine leukemia virus envelope protein influences the
      conformation of the extracellular domain: implications for mechanism of action of
      the R Peptide.
AB  - The envelope (Env) protein of Moloney murine leukemia virus (MoMuLV) is a
      homotrimeric complex whose monomers consist of linked surface (SU) and
      transmembrane (TM) proteins cleaved from a precursor protein by a cellular
      protease. In addition, a significant fraction of virion-associated TM is further
      processed by the viral protease to remove the C-terminal 16 amino acids of the
      cytoplasmic domain, the R peptide. This cleavage greatly enhances the
      fusogenicity of the protein and is necessary for the formation of a fully
      functional Env protein complex. We have previously proposed that R peptide
      cleavage enhances fusogenicity by altering the conformation of the ectodomain of
      the protein (Y. Zhao et al., J. Virol. 72:5392-5398, 1998). Using a series of
      truncation and point mutants of MoMuLV Env, we now provide direct biochemical and
      immunological evidence that the cytoplasmic tail and the membrane-spanning region
      of Env can influence the overall structure of the ectodomain of the protein and
      alter the strength of the SU-TM interaction. The R-peptide-truncated form of the
      protein, in particular, exhibits a markedly different conformation than the full
      length protein.

PMID- 12502846
TI  - The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) functions as a
      dominant regulator of apoptosis in hippocampal neurons involving activation of
      the ERK survival pathway and upregulation of the antiapoptotic protein Bag-1.
AB  - Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) can trigger or block
      apoptosis in a cell type-dependent manner. We have recently shown that the
      protein kinase activity of the large subunit of the HSV-2 ribonucleotide
      reductase (R1) protein (ICP10 PK) blocks apoptosis in cultured hippocampal
      neurons by activating the extracellular signal-regulated kinase (ERK) survival
      pathway (Perkins et al., J. Virol. 76:1435-1449, 2002). The present studies were
      designed to better elucidate the mechanism of ICP10 PK-induced neuroprotection
      and determine whether HSV-1 has similar activity. The data indicate that
      apoptosis inhibition by ICP10 PK involves a c-Raf-1-dependent mechanism and
      induction of the antiapoptotic protein Bag-1 by the activated ERK survival
      pathway. Also associated with neuroprotection by ICP10 PK are increased
      activation/stability of the transcription factor CREB and stabilization of the
      antiapoptotic protein Bcl-2. HSV-1 and the ICP10 PK-deleted HSV-2 mutant
      ICP10DeltaPK activate JNK, c-Jun, and ATF-2, induce the proapoptotic protein BAD,
      and trigger apoptosis in hippocampal neurons. c-Jun activation and apoptosis are
      inhibited in hippocampal cultures infected with HSV-1 in the presence of the JNK
      inhibitor SP600125, suggesting that JNK/c-Jun activation is required for HSV-1
      induced apoptosis. Ectopically delivered ICP10 PK (but not its PK-negative mutant
      p139) inhibits apoptosis triggered by HSV-1 or ICP10DeltaPK. Collectively, the
      data indicate that ICP10 PK-induced activation of the ERK survival pathway
      results in Bag-1 upregulation and overrides the proapoptotic JNK/c-Jun signal
      induced by other viral proteins.

PMID- 12502847
TI  - Viability of a drug-resistant human immunodeficiency virus type 1 protease
      variant: structural insights for better antiviral therapy.
AB  - Under the selective pressure of protease inhibitor therapy, patients infected
      with human immunodeficiency virus (HIV) often develop drug-resistant HIV strains.
      One of the first drug-resistant mutations to arise in the protease, particularly
      in patients receiving indinavir or ritonavir treatment, is V82A, which
      compromises the binding of these and other inhibitors but allows the virus to
      remain viable. To probe this drug resistance, we solved the crystal structures of
      three natural substrates and two commercial drugs in complex with an inactive
      drug-resistant mutant (D25N/V82A) HIV-1 protease. Through structural analysis and
      comparison of the protein-ligand interactions, we found that Val82 interacts more
      closely with the drugs than with the natural substrate peptides. The V82A
      mutation compromises these interactions with the drugs while not greatly
      affecting the substrate interactions, which is consistent with previously
      published kinetic data. Coupled with our earlier observations, these findings
      suggest that future inhibitor design may reduce the probability of the appearance
      of drug-resistant mutations by targeting residues that are essential for
      substrate recognition.

PMID- 12502848
TI  - TRAF1 is a critical regulator of JNK signaling by the TRAF-binding domain of the
      Epstein-Barr virus-encoded latent infection membrane protein 1 but not CD40.
AB  - The oncogenic Epstein-Barr virus (EBV)-encoded latent infection membrane protein
      1 (LMP1) mimics a constitutive active tumor necrosis factor (TNF) family receptor
      in its ability to recruit TNF receptor-associated factors (TRAFs) and TNF
      receptor-associated death domain protein (TRADD) in a ligand-independent manner.
      As a result, LMP1 constitutively engages signaling pathways, such as the JNK and
      p38 mitogen-activated protein kinases (MAPK), the transcription factor NF-kappaB,
      and the JAK/STAT cascade, and these activities may explain many of its
      pleiotropic effects on cell phenotype, growth, and transformation. In this study
      we demonstrate the ability of the TRAF-binding domain of LMP1 to signal on the
      JNK/AP-1 axis in a cell type- dependent manner that critically involves TRAF1 and
      TRAF2. Thus, expression of this LMP1 domain in TRAF1-positive lymphoma cells
      promotes significant JNK activation, which is blocked by dominant-negative TRAF2
      but not TRAF5. However, TRAF1 is absent in many established epithelial cell lines
      and primary nasopharyngeal carcinoma (NPC) biopsy specimens. In these cells, JNK
      activation by the TRAF-binding domain of LMP1 depends on the reconstitution of
      TRAF1 expression. The critical role of TRAF1 in the regulation of TRAF2-dependent
      JNK signaling is particular to the TRAF-binding domain of LMP1, since a
      homologous region in the cytoplasmic tail of CD40 or the TRADD-interacting domain
      of LMP1 signal on the JNK axis independently of TRAF1 status. These data further
      dissect the signaling components used by LMP1 and identify a novel role for TRAF1
      as a modulator of oncogenic signals.

PMID- 12502849
TI  - Negative-strand tospoviruses and tenuiviruses carry a gene for a suppressor of
      gene silencing at analogous genomic positions.
AB  - Posttranscriptional silencing of a green fluorescent protein (GFP) transgene in
      Nicotiana benthamiana plants was suppressed when these plants were infected with
      Tomato spotted wilt virus (TSWV), a plant-infecting member of the BUNYAVIRIDAE:
      Infection with TSWV resulted in complete reactivation of GFP expression, similar
      to the case for Potato virus Y, but distinct from that for Cucumber mosaic virus,
      two viruses known to carry genes encoding silencing suppressor proteins.
      Agrobacterium-based leaf injections with individual TSWV genes identified the
      NS(S) gene to be responsible for the RNA silencing-suppressing activity displayed
      by this virus. The absence of short interfering RNAs in NS(S)-expressing leaf
      sectors suggests that the tospoviral NS(S) protein interferes with the intrinsic
      RNA silencing present in plants. Suppression of RNA silencing was also observed
      when the NS3 protein of the Rice hoja blanca tenuivirus, a nonenveloped negative
      strand virus, was expressed. These results indicate that plant-infecting negative
      strand RNA viruses carry a gene for a suppressor of RNA silencing.

PMID- 12502850
TI  - Differential N-linked glycosylation of human immunodeficiency virus and Ebola
      virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR.
AB  - The C-type lectins DC-SIGN and DC-SIGNR [collectively referred to as DC-SIGN(R)]
      bind and transmit human immunodeficiency virus (HIV) and simian immunodeficiency
      virus to T cells via the viral envelope glycoprotein (Env). Other viruses
      containing heavily glycosylated glycoproteins (GPs) fail to interact with DC
      SIGN(R), suggesting some degree of specificity in this interaction. We show here
      that DC-SIGN(R) selectively interact with HIV Env and Ebola virus GPs containing
      more high-mannose than complex carbohydrate structures. Modulation of N-glycans
      on Env or GP through production of viruses in different primary cells or in the
      presence of the mannosidase I inhibitor deoxymannojirimycin dramatically affected
      DC-SIGN(R) infectivity enhancement. Further, murine leukemia virus, which
      typically does not interact efficiently with DC-SIGN(R), could do so when
      produced in the presence of deoxymannojirimycin. We predict that other viruses
      containing GPs with a large proportion of high-mannose N-glycans will efficiently
      interact with DC-SIGN(R), whereas those with solely complex N-glycans will not.
      Thus, the virus-producing cell type is an important factor in dictating both N
      glycan status and virus interactions with DC-SIGN(R), which may impact virus
      tropism and transmissibility in vivo.

PMID- 12502851
TI  - Contrasting roles of endosomal pH and the cytoskeleton in infection of human
      glial cells by JC virus and simian virus 40.
AB  - Infection of eukaryotic cells by pathogens requires the efficient use of host
      cell endocytic and cytoplasmic transport mechanisms. Understanding how these
      cellular functions are exploited by microorganisms allows us to better define the
      basic biology of pathogenesis while providing better insight into normal cellular
      functions. In this report we compare and contrast intracellular transport and
      trafficking of the human polyomavirus JC virus (JCV) with that of simian virus 40
      (SV40). We have previously shown that infection of human glial cells by JCV
      requires clathrin-dependent endocytosis. In contrast, infection of cells by SV40
      proceeds by caveola-dependent endocytosis. We now examine the roles of endosomal
      pH and the cellular cytoskeleton during infection of glial cells by both viruses.
      Our results demonstrate that JCV infection is sensitive to disruption of
      endosomal pH, whereas SV40 infection is pH independent. Infection by JCV is
      inhibited by treatment of glial cells with cytochalasin D, nocodazole, and
      acrylamide, whereas SV40 infection is affected only by nocodazole. These data
      point to critical differences between JCV and SV40 in terms of endocytosis and
      intracellular trafficking of their DNA genomes to the nucleus. These data also
      suggest a unique sequential involvement of cytoskeletal elements during infection
      of glial cells by JCV.

PMID- 12502852
TI  - Mouse cytomegalovirus immediate-early protein 1 binds with host cell repressors
      to relieve suppressive effects on viral transcription and replication during
      lytic infection.
AB  - Herpesviruses start their transcriptional cascade at nuclear domain 10 (ND10).
      The deposition of virus genomes at these nuclear sites occurs due to the binding
      of the interferon-inducible repressor protein promyelocytic leukemia protein
      (PML) and/or Daxx to a viral DNA-protein complex. However, the presence of
      repressive proteins at the nuclear site of virus transcription has remained
      unexplained. We investigated the mouse cytomegalovirus (MCMV) immediate-early 1
      protein (IE1), which is necessary for productive infection at low multiplicities
      of infection and therefore likely to be involved in overcoming cellular
      repression. Temporal analysis of IE1 distribution revealed its initial
      segregation into ND10 by binding to PML and/or Daxx and IE1-dependent recruitment
      of the transcriptional repressor histone deacetylase-2 (HDAC-2) to this site.
      However, these protein aggregates are dissociated in cells producing sufficient
      IE1 through titration of PML, Daxx, and HDAC-2. Importantly, binding of IE1 to
      HDAC-2 decreased deacetylation activity. Moreover, inhibition of HDAC by
      trichostatin-A resulted in an increase in viral protein synthesis, an increase in
      cells starting the formation of prereplication compartments, and an increase in
      the total infectious viruses produced. Thus, IE1, like trichostatin-A, reverses
      the repressive effect of HDAC evident in the presence of acetylated histones in
      the immediate-early promoter region. Since HDAC also binds to the promoter region
      of IE1, as determined by the chromatin immunoprecipitation assay, these combined
      results suggest that IE1 inhibits or reverses HDAC-mediated repression of the
      infecting viral genomes, possibly by a process akin to activation of
      heterochromatin. We propose that even permissive cells can repress transcription
      of infecting viral genomes through repressors, including HDAC, Daxx, and PML, and
      the segregation of IE1 to ND10 that would inactivate those repressors. The virus
      can counter this repression by overexpressing IE1 when present in sufficient copy
      number, thus reducing the availability and effectiveness of these repressors.

PMID- 12502853
TI  - Polymorphism and structural maturation of bunyamwera virus in Golgi and post
      Golgi compartments.
AB  - The Golgi apparatus is the assembly site for a number of complex enveloped
      viruses. Using high-preservation methods for electron microscopy, we have
      detected two previously unknown maturation steps in the morphogenesis of
      Bunyamwera virus in BHK-21 cells. The first maturation takes place inside the
      Golgi stack, where annular immature particles transform into dense, compact
      structures. Megalomicin, a drug that disrupts the trans side of the Golgi
      complex, reversibly blocks transformation, showing that a functional trans-Golgi
      is needed for maturation. The second structural change seems to take place during
      the egress of viral particles from cells, when a coat of round-shaped spikes
      becomes evident. A fourth viral assembly was detected in infected cells: rigid
      tubular structures assemble in the Golgi region early in infection and frequently
      connect with mitochondria. In Vero cells, the virus induces an early and
      spectacular fragmentation of intracellular membranes while productive infection
      progresses. Assembly occurs in fragmented Golgi stacks and generates tubular
      structures, as well as the three spherical viral forms. These results, together
      with our previous studies with nonrelated viruses, show that the Golgi complex
      contains key factors for the structural transformation of a number of enveloped
      viruses that assemble intracellularly.

PMID- 12502854
TI  - Construction of an excisable bacterial artificial chromosome containing a full
      length infectious clone of herpes simplex virus type 1: viruses reconstituted
      from the clone exhibit wild-type properties in vitro and in vivo.
AB  - In recent years, several laboratories have reported on the cloning of herpes
      simplex virus type 1 (HSV-1) genomes as bacterial artificial chromosomes (BACs)
      in Escherichia coli and on procedures to manipulate these genomes by using the
      bacterial recombination machinery. However, the HSV-BACs reported so far are
      either replication incompetent or infectious, with a deletion of one or more
      viral genes due to the BAC vector insertion. For use as a multipurpose clone in
      research on HSV-1, we attempted to generate infectious HSV-BACs containing the
      full genome of HSV-1 without any loss of viral genes. Our results were as
      follows. (i) E. coli (YEbac102) harboring the full-length HSV-1 genome
      (pYEbac102) in which a BAC flanked by loxP sites was inserted into the intergenic
      region between U(L)3 and U(L)4 was constructed. (ii) pYEbac102 was an infectious
      molecular clone, given that its transfection into rabbit skin cells resulted in
      production of infectious virus (YK304). (iii) The BAC vector sequence was almost
      perfectly excisable from the genome of the reconstituted virus YK304 by
      coinfection of Vero cells with YK304 and a recombinant adenovirus, AxCANCre,
      expressing Cre recombinase. (iv) As far as was examined, the reconstituted
      viruses from pYEbac102 could not be phenotypically differentiated from wild-type
      viruses in vitro and in vivo. Thus, the viruses grew as well in Vero cells as did
      the wild-type virus and exhibited wild-type virulence in mice on intracerebral
      inoculation. (v) The infectious molecular clone pYEbac102 is in fact useful for
      mutagenesis of the HSV-1 genome by bacterial genetics, and a recombinant virus
      carrying amino acid substitutions in both copies of the alpha0 gene was
      generated. pYEbac102 will have multiple applications to the rapid generation of
      genetically engineered HSV-1 recombinants in basic research into HSV-1 and in the
      development of HSV vectors in human therapy.

PMID- 12502855
TI  - Cellular gene expression upon human immunodeficiency virus type 1 infection of
      CD4(+)-T-cell lines.
AB  - The expression levels of approximately 4,600 cellular RNA transcripts were
      assessed in CD4(+)-T-cell lines at different times after infection with human
      immunodeficiency virus type 1 strain BRU (HIV-1(BRU)) using DNA microarrays. We
      found that several classes of genes were inhibited by HIV-1(BRU) infection,
      consistent with the G(2) arrest of HIV-1-infected cells induced by Vpr. These
      included genes involved in cell division and transcription, a family of DEAD-box
      proteins (RNA helicases), and all genes involved in translation and splicing.
      However, the overall level of cell activation and signaling was increased in
      infected cells, consistent with strong virus production. These included a
      subgroup of transcription factors, including EGR1 and JUN, suggesting they play a
      specific role in the HIV-1 life cycle. Some regulatory changes were cell line
      specific; however, the majority, including enzymes involved in cholesterol
      biosynthesis, of changes were regulated in most infected cell lines. Compendium
      analysis comparing gene expression profiles of our HIV-1 infection experiments to
      those of cells exposed to heat shock, interferon, or influenza A virus indicated
      that HIV-1 infection largely induced specific changes rather than simply
      activating stress response or cytokine response pathways. Thus, microarray
      analysis confirmed several known HIV-1 host cell interactions and permitted
      identification of specific cellular pathways not previously implicated in HIV-1
      infection. Continuing analyses are expected to suggest strategies for impacting
      HIV-1 replication in vivo by targeting these pathways.

PMID- 12502856
TI  - The attenuated pseudorabies virus strain Bartha fails to package the tegument
      proteins Us3 and VP22.
AB  - The Bartha strain of pseudorabies virus has several recognized mutations,
      including a deletion in the unique short region encompassing the glycoprotein I
      (gI), gE, Us9, and Us2 genes and point mutations in the gC, gM, and UL21 genes.
      We have determined that Bartha has mutations in the serine/threonine kinase
      encoded by the Us3 gene relative to the wild-type Becker strain. Our analysis
      revealed that Becker virions contain the Us3 protein, whereas Bartha virions do
      not. To test whether the mutations in the Bartha Us3 protein were responsible for
      this observation, we constructed a recombinant Bartha strain, PRV632, which
      expresses the Becker Us3 protein. PRV632 failed to package Us3 into the tegument,
      indicating that mutations other than those in the Us3 primary amino acid sequence
      were responsible for the failure of Bartha to package its Us3 protein. A
      recombinant Becker strain, PRV634, which expresses the Bartha Us3 protein, was
      constructed to test whether it was capable of being packaged into virions. The
      Bartha Us3 protein was not incorporated into PRV634 virions efficiently,
      suggesting that the primary sequence of the Bartha Us3 protein affects packaging
      into the tegument. To determine whether the packaging of other tegument proteins
      was affected in the Bartha strain, we examined VP22. Whereas Becker packaged VP22
      into virions, Bartha had a severe deficiency in VP22 incorporation. Analysis of
      VP22 expression in Bartha-infected cells revealed that Bartha VP22 had a slower
      mobility on sodium dodecyl sulfate-polyacrylamide gels, indicating either primary
      sequence differences and/or different posttranslational modifications relative to
      Becker VP22. Taken together, these data indicate that, while the primary sequence
      of the Us3 protein does affect its incorporation into the tegument, other factors
      are involved. Furthermore, our data suggest that one or more of the gI, gE, Us9,
      or Us2 genes influences the localization of the Us3 protein in infected cells,
      and this effect may be important for the proper incorporation of Us3 into
      virions.

PMID- 12502857
TI  - The 3C-like proteinase of an invertebrate nidovirus links coronavirus and
      potyvirus homologs.
AB  - Gill-associated virus (GAV), a positive-stranded RNA virus of prawns, is the
      prototype of newly recognized taxa (genus Okavirus, family Roniviridae) within
      the order NIDOVIRALES: In this study, a putative GAV cysteine proteinase (3C-like
      proteinase [3CL(pro)]), which is predicted to be the key enzyme involved in
      processing of the GAV replicase polyprotein precursors, pp1a and pp1ab, was
      characterized. Comparative sequence analysis indicated that, like its coronavirus
      homologs, 3CL(pro) has a three-domain organization and is flanked by hydrophobic
      domains. The putative 3CL(pro) domain including flanking regions (pp1a residues
      2793 to 3143) was fused to the Escherichia coli maltose-binding protein (MBP)
      and, when expressed in E. coli, was found to possess N-terminal autoprocessing
      activity that was not dependent on the presence of the 3CL(pro) C-terminal
      domain. N-terminal sequence analysis of the processed protein revealed that
      cleavage occurred at the location (2827)LVTHE downward arrow VRTGN(2836). The
      trans-processing activity of the purified recombinant 3CL(pro) (pp1a residues
      2832 to 3126) was used to identify another cleavage site, (6441)KVNHE downward
      arrow LYHVA(6450), in the C-terminal pp1ab region. Taken together, the data
      tentatively identify VxHE downward arrow (L,V) as the substrate consensus
      sequence for the GAV 3CL(pro). The study revealed that the GAV and potyvirus
      3CL(pro)s possess similar substrate specificities which correlate with structural
      similarities in their respective substrate-binding sites, identified in sequence
      comparisons. Analysis of the proteolytic activities of MBP-3CL(pro) fusion
      proteins carrying replacements of putative active-site residues provided evidence
      that, in contrast to most other 3C/3CL(pro)s but in common with coronavirus
      3CL(pro)s, the GAV 3CL(pro) employs a Cys(2968)-His(2879) catalytic dyad. The
      properties of the GAV 3CL(pro) define a novel RNA virus proteinase variant that
      bridges the gap between the distantly related chymotrypsin-like cysteine
      proteinases of coronaviruses and potyviruses.

PMID- 12502858
TI  - The PHD/LAP-domain protein M153R of myxomavirus is a ubiquitin ligase that
      induces the rapid internalization and lysosomal destruction of CD4.
AB  - The genomes of several poxviruses contain open reading frames with homology to
      the K3 and K5 genes of Kaposi's sarcoma-associated herpesvirus (KSHV) and the K3
      gene of murine gammaherpesvirus 68, which target major histocompatibility complex
      class I (MHC-I) as well as costimulatory molecules for proteasomal or lysosomal
      degradation. The homologous gene product of myxomavirus (MV), M153R, was recently
      shown to reduce the cell surface expression of MHC-I. In addition, normal MHC-I
      surface expression was observed in cells infected with MV lacking M153R (J. L.
      Guerin, J. Gelfi, S. Boullier, M. Delverdier, F. A. Bellanger, S. Bertagnoli, I.
      Drexler, G. Sutter, and F. Messud-Petit, J. Virol. 76:2912-2923, 2002). Here, we
      show that M153R also downregulates the T-cell coreceptor CD4 and we study the
      molecular mechanism by which M153R achieves the downregulation of CD4 and MHC-I.
      Upon M153R expression, CD4 was rapidly internalized and degraded in lysosomes,
      whereas deletion of M153R from the genome of MV restored CD4 expression. The
      downregulation of both CD4 and MHC-I was dependent on the presence of lysine
      residues in their cytoplasmic tails. Increased ubiquitination of CD4 was observed
      upon coexpression with M153R in the presence of inhibitors of lysosomal
      acidification. Surface expression of CD4 was restored upon overexpression of Hrs,
      a ubiquitin interaction motif-containing protein that sorts ubiquitinated
      proteins into endosomes. Moreover, the purified PHD/LAP zinc finger of M153R
      catalyzed the formation of multiubiquitin adducts in vitro. Our data suggest that
      M153R acts as a membrane-bound ubiquitin ligase that conjugates ubiquitin to the
      cytoplasmic domain of substrate glycoproteins, with ubiquitin serving as a
      lysosomal targeting signal. Since a similar mechanism was recently proposed for
      KSHV K5, it seems that members of the unrelated families of gamma-2 herpesviruses
      and poxviruses share a common immune evasion mechanism that targets host cell
      immune receptors.

PMID- 12502859
TI  - Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta:
      physical association and promoter-dependent transcriptional repression.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus that
      has been implicated in the pathogenesis of Kaposi's sarcoma and B-cell neoplasms.
      The genomic organization of KSHV is similar to that of Epstein-Barr virus (EBV).
      EBV encodes two transcriptional factors, Rta and Zta, which functionally interact
      to transactivate EBV genes during replication and reactivation from latency. KSHV
      encodes a basic leucine zipper protein (K-bZIP), a homologue of EBV Zta, and K
      Rta, the homologue of EBV Rta. EBV Rta and Zta are strong transcriptional
      transactivators. Although there is ample evidence that K-Rta is a potent
      transactivator, the role of K-bZIP as a transcriptional factor is much less
      clear. In this study, we report that K-bZIP modulates K-Rta function. We show
      that K-bZIP directly interacts with K-Rta in vivo and in vitro. This association
      is specific, requiring the basic domain (amino acids 122 to 189) of K-bZIP and a
      specific region (amino acids 499 to 550) of K-Rta, and can be detected with K
      bZIP and K-Rta endogenously expressed in BCBL-1 cells treated with tetradecanoyl
      phorbol acetate. The functional relevance of this association was revealed by the
      observation that K-bZIP represses the transactivation of the ORF57 promoter by K
      Rta in a dose-dependent manner. K-bZIP lacking the interaction domain fails to
      repress K-Rta-mediated transactivation; this finding attests to the specificity
      of the repression. Interestingly, this repression is not observed for the
      promoter of polyadenylated nuclear (PAN) RNA, another target of K-Rta; thus,
      repression is promoter dependent. Finally, we provide evidence that the
      modulation of K-Rta by K-bZIP also occurs in vivo during reactivation of the
      viral genome in BCBL-1 cells. When K-bZIP is overexpressed in BCBL-1 cells, the
      level of expression of ORF57 but not PAN RNA is repressed. These data support the
      model that one function of K-bZIP is to modulate the activity of the
      transcriptional transactivator K-Rta.

PMID- 12502860
TI  - Defective tobamovirus movement protein lacking wild-type phosphorylation sites
      can be complemented by substitutions found in revertants.
AB  - We reported previously that the movement protein (MP) of tomato mosaic
      tobamovirus is phosphorylated, and we proposed that MP phosphorylation is
      important for viral pathogenesis. Experimental data indicated that
      phosphorylation enhances the stability of MP in vivo and enables the protein to
      assume the correct intracellular location to perform its function. A mutant virus
      designated 37A238A was constructed; this virus lacked two serine residues within
      the MP, which prevented its phosphorylation. In the present study, we inoculated
      plants with the 37A238A mutant, and as expected, it was unable to produce local
      lesions on the leaves. However, after an extended period, we found that lesions
      did occur, which were due to revertant viruses. Several revertants were isolated,
      and the genetic changes in their MPs were examined together with any changes in
      their in vivo characteristics. We found that reversion to virulence was
      associated first with increased MP stability in infected cells and second with a
      shift in MP intracellular localization over time. In one case, the revertant MP
      was not phosphorylated in vivo, but it was functional.

PMID- 12502861
TI  - Molecular characterization of a hamster viscerotropic strain of yellow fever
      virus.
AB  - A hamster viscerotropic strain of yellow fever (YF) virus has been derived after
      serial passage of strain Asibi through hamsters. The parental Asibi/hamster p0
      virus causes a mild and transient viremia in hamsters with no outward, clinical
      signs of illness. In contrast, the viscerotropic Asibi/hamster p7 virus causes a
      robust viremia, severe illness, and death in subadult hamsters. The genome of the
      hamster viscerotropic Asibi/hamster p7 virus has been sequenced and compared with
      the parental nonviscerotropic Asibi/hamster p0 virus identifying 14 nucleotide
      changes encoding only seven amino acid substitutions. The majority of these
      substitutions (five of seven) fall within the envelope (E) protein at positions
      Q27H, D28G, D155A, K323R, and K331R. These results support an important role for
      the E protein in determining YF virus viscerotropism.

PMID- 12502862
TI  - Human immunodeficiency virus type 1 nucleocapsid zn(2+) fingers are required for
      efficient reverse transcription, initial integration processes, and protection of
      newly synthesized viral DNA.
AB  - Human immunodeficiency virus type 1 (HIV-1) containing mutations in the
      nucleocapsid (NC) Zn(2+) finger domains have greatly reduced infectivity, even
      though genome packaging is largely unaffected in certain cases. To examine
      replication defects, viral DNA (vDNA) was isolated from cells infected with
      viruses containing His-to-Cys changes in their Zn(2+) fingers (NC(H23C) and
      NC(H44C)), an integrase mutant (IN(D116N)), a double mutant (NC(H23C)/IN(D116N)),
      or wild-type HIV-1. In vitro assays have established potential roles for NC in
      reverse transcription and integration. In vivo results for these processes were
      obtained by quantitative PCR, cloning of PCR products, and comparison of the
      quantity and composition of vDNA generated at discrete points during reverse
      transcription. Quantitative analysis of the reverse transcription intermediates
      for these species strongly suggests decreased stability of the DNA produced. Both
      Zn(2+) finger mutants appear to be defective in DNA synthesis, with the minus-
      and plus-strand transfer processes being affected while interior portions of the
      vDNA remain more intact. Sequences obtained from PCR amplification and cloning of
      2-LTR circle junction fragments revealed that the NC mutants had a phenotype
      similar to the IN mutant; removal of the terminal CA dinucleotides necessary for
      integration of the vDNA is disabled by the NC mutations. Thus, the loss of
      infectivity in these NC mutants in vivo appears to result from defective reverse
      transcription and integration processes stemming from decreased protection of the
      full-length vDNA. Finally, these results indicate that the chaperone activity of
      NC extends from the management of viral RNA through to the full-length vDNA.

PMID- 12502863
TI  - CCAAT/enhancer binding protein alpha interacts with ZTA and mediates ZTA-induced
      p21(CIP-1) accumulation and G(1) cell cycle arrest during the Epstein-Barr virus
      lytic cycle.
AB  - Cellular CCAAT/enhancer binding protein alpha (C/EBPalpha) promotes cellular
      differentiation and has antimitotic activities involving cell cycle arrest at
      G(1)/S through stabilization of p21(CIP-1)/WAF1 and through transcriptional
      activation of the p21 promoter. The Epstein-Barr virus lytic-cycle transactivator
      protein ZTA is known to arrest the host cell cycle at G(1)/S via a p53
      independent p21 pathway, but the detailed molecular mechanisms involved have not
      been defined. To further evaluate the role of ZTA in cell cycle arrest, we
      constructed a recombinant adenovirus vector expressing ZTA (Ad-ZTA), whose level
      of expression at a low multiplicity of infection in normal human diploid
      fibroblast (HF) cells was lower than or equal to the physiological level seen in
      Akata cells lytically induced by EBV (EBV-Akata cells). Fluorescence-activated
      cell sorting analysis of HF cells infected with Ad-ZTA confirmed that G(1)/S cell
      cycle arrest occurred in the majority of ZTA-positive cells, but not with an
      adenovirus vector expressing green fluorescent protein. Double-label
      immunofluorescence assays (IFA) performed with Ad-ZTA-infected HF cells revealed
      that only ZTA-positive cells induced the expression of both endogenous C/EBPalpha
      and p21 and blocked the progression into S phase, as detected by a lack of
      incorporation of bromodeoxyuridine. The stimulation of endogenous ZTA protein
      expression either through treatment with tetradecanoyl phorbol acetate in D98/HR1
      cells or through B-cell receptor cross-linking with anti-immunoglobulin G
      antibody in EBV-Akata cells also coincided with the induction of both C/EBPalpha
      and p21 and their mRNAs, as assayed by Northern blot, Western blot, and IFA
      experiments. Mechanistically, the ZTA protein proved to directly interact with
      C/EBPalpha by coimmunoprecipitation in EBV-Akata cells and with DNA-bound
      C/EBPalpha in electrophoretic mobility shift assay experiments, and the in vitro
      interaction domain encompassed the basic leucine zipper domain of ZTA. ZTA also
      specifically protected C/EBPalpha from degradation in a protein stability assay
      with a non-EBV-induced Akata cell proteasome extract. Furthermore, both
      C/EBPalpha and ZTA were found to specifically associate with the C/EBPalpha
      promoter in chromatin immunoprecipitation assays, but the interaction with ZTA
      appeared to be mediated by C/EBPalpha because it was abolished by clearing with
      anti-C/EBPalpha antibody. ZTA did not bind to or activate the C/EBPalpha promoter
      directly but cooperatively enhanced the positive autoregulation of the C/EBPalpha
      promoter by cotransfected C/EBPalpha in transient luciferase reporter gene assays
      with Vero and HeLa cells as well as with DG75 B lymphocytes. Similarly, ZTA alone
      had little effect on the p21 promoter in transient reporter gene assays, but in
      the presence of cotransfected C/EBPalpha, ZTA enhanced the level of C/EBPalpha
      activation. This effect proved to require a previously unrecognized region in the
      proximal p21 promoter that contains three high-affinity C/EBPalpha binding sites.
      Finally, in C/EBPalpha-deficient mouse embryonic fibroblasts (MEF), Ad-ZTA was
      unable to induce either p21 or G(1) arrest, whereas it was able to induce both in
      wild-type MEF. Overall, we conclude that C/EBPalpha is essential for at least one
      pathway of ZTA-induced G(1) arrest during EBV lytic-cycle DNA replication and
      that this process involves a physical piggyback interaction between ZTA and
      C/EBPalpha leading to greatly enhanced C/EBPalpha and p21 levels through both
      transcriptional and posttranslational mechanisms.

PMID- 12502864
TI  - Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist
      activity for the NDV V protein and the Nipah virus V, W, and C proteins.
AB  - We have generated a recombinant Newcastle disease virus (NDV) that expresses the
      green fluorescence protein (GFP) in infected chicken embryo fibroblasts (CEFs).
      This virus is interferon (IFN) sensitive, and pretreatment of cells with chicken
      alpha/beta IFN (IFN-alpha/beta) completely blocks viral GFP expression. Prior
      transfection of plasmid DNA induces an IFN response in CEFs and blocks NDV-GFP
      replication. However, transfection of known inhibitors of the IFN-alpha/beta
      system, including the influenza A virus NS1 protein and the Ebola virus VP35
      protein, restores NDV-GFP replication. We therefore conclude that the NDV-GFP
      virus could be used to screen proteins expressed from plasmids for the ability to
      counteract the host cell IFN response. Using this system, we show that expression
      of the NDV V protein or the Nipah virus V, W, or C proteins rescues NDV-GFP
      replication in the face of the transfection-induced IFN response. The V and W
      proteins of Nipah virus, a highly lethal pathogen in humans, also block
      activation of an IFN-inducible promoter in primate cells. Interestingly, the
      amino-terminal region of the Nipah virus V protein, which is identical to the
      amino terminus of Nipah virus W, is sufficient to exert the IFN-antagonist
      activity. In contrast, the anti-IFN activity of the NDV V protein appears to be
      located in the carboxy-terminal region of the protein, a region implicated in the
      IFN-antagonist activity exhibited by the V proteins of mumps virus and human
      parainfluenza virus type 2.

PMID- 12502865
TI  - Amino acid substitutions at position 190 of human immunodeficiency virus type 1
      reverse transcriptase increase susceptibility to delavirdine and impair virus
      replication.
AB  - Suboptimal treatment of human immunodeficiency virus type 1 (HIV-1) infection
      with nonnucleoside reverse transcriptase inhibitors (NNRTI) often results in the
      rapid selection of drug-resistant virus. Several amino acid substitutions at
      position 190 of reverse transcriptase (RT) have been associated with reduced
      susceptibility to the NNRTI, especially nevirapine (NVP) and efavirenz (EFV). In
      the present study, the effects of various 190 substitutions observed in viruses
      obtained from NNRTI-experienced patients were characterized with patient-derived
      HIV isolates and confirmed with a panel of isogenic viruses. Compared to wild
      type HIV, which has a glycine at position 190 (G190), viruses with 190
      substitutions (A, C, Q, S, V, E, or T, collectively referred to as G190X
      substitutions) were markedly less susceptible to NVP and EFV. In contrast,
      delavirdine (DLV) susceptibility of these G190X viruses increased from 3 to 300
      fold (hypersusceptible) or was only slightly decreased. The replication capacity
      of viruses with certain 190 substitutions (C, Q, V, T, and E) was severely
      impaired and was correlated with reduced virion-associated RT activity and
      incomplete protease (PR) processing of the viral p55(gag) polyprotein. These
      defects were the result of inadequate p160(gagpol) incorporation into virions.
      Compensatory mutations within RT and PR improved replication capacity, p55(gag)
      processing, and RT activity, presumably through increased incorporation of
      p160(gagpol) into virions. We observe an inverse relationship between the degree
      of NVP and EFV resistance and the impairment of viral replication in viruses with
      substitutions at 190 in RT. These observations may have important implications
      for the future design and development of antiretroviral drugs that restrict the
      outgrowth of resistant variants with high replication capacity.

PMID- 12502866
TI  - Kaposi's sarcoma-associated herpesvirus induces the phosphatidylinositol 3-kinase
      PKC-zeta-MEK-ERK signaling pathway in target cells early during infection:
      implications for infectivity.
AB  - Human herpesvirus 8 (HHV-8) is implicated in the pathogenesis of Kaposi's
      sarcoma. HHV-8 envelope glycoprotein B (gB) possesses the RGD motif known to
      interact with integrin molecules, and HHV-8 infectivity was inhibited by RGD
      peptides, by antibodies against alpha3 and beta1 integrins, and by soluble
      alpha3beta1 integrin (S. M. Akula, N. P. Pramod, F.-Z. Wang, and B. Chandran,
      Cell 108:407-419, 2002). Anti-gB antibodies immunoprecipitated the virus alpha3
      and beta1 complexes, and virus-binding studies suggest a role for alpha3beta1 in
      HHV-8 entry. HHV-8 infection induced the integrin-mediated activation of focal
      adhesion kinase (FAK), implicating a role for integrin and the associated
      signaling pathways in HHV-8 entry into the target cells. Immediately after
      infection, target cells exhibited morphological changes and cytoskeletal
      rearrangements, suggesting the induction of signal pathways. As early as 5 min
      postinfection, HHV-8 activated the MEK-ERK1/2 pathway. The focal adhesion
      components phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase C-zeta
      (PKC-zeta) were recruited as upstream mediators of the HHV-8-induced ERK pathway.
      Anti-HHV-8 gB-neutralizing antibodies and soluble alpha3beta1 integrin inhibited
      the virus-induced signaling pathways. Early kinetics of the cellular signaling
      pathway and its activation by UV-inactivated HHV-8 suggest a role for virus
      binding and/or entry but not viral gene expression in this induction. Studies
      with human alpha3 integrin-transfected Chinese hamster ovary cells and FAK
      negative mouse DU3 cells suggest that the alpha3beta1 integrin and FAK play roles
      in the HHV-8 mediated signal induction. Inhibitors specific for PI 3-kinase, PKC
      zeta, MEK, and ERK significantly reduced the virus infectivity without affecting
      virus binding to the target cells. Examination of viral DNA entry suggests a role
      for PI 3-kinase in HHV-8 entry into the target cells and a role for PKC-zeta,
      MEK, and ERK at a post-viral entry stage of infection. These findings implicate a
      critical role for integrin-associated mitogenic signaling in HHV-8's infection of
      target cells and suggest that, by orchestrating the signal cascade, HHV-8 may
      create an appropriate intracellular environment to facilitate the infection.

PMID- 12502867
TI  - Persistent Sin Nombre virus infection in the deer mouse (Peromyscus maniculatus)
      model: sites of replication and strand-specific expression.
AB  - To address Sin Nombre (SN) virus persistence in deer mice, we sacrificed
      experimentally infected deer mice at eight time points from day 21 to day 217
      postinoculation (p.i.) and examined their tissues for viral nucleocapsid (N)
      antigen expression and both negative-strand (genomic) and positive-strand
      (replicative/mRNA) viral S segment RNA titers. All the animals that we inoculated
      developed persistent infections, and SN virus could be isolated from tissues
      throughout the course of infection. The transition from an acute to a persistent
      pattern of infection appeared to occur between days 60 and 90 p.i. Beginning on
      day 60 p.i., the heart, brown adipose tissue (BAT), and lung retained antigen
      expression and genomic viral RNA the most frequently. We found a statistically
      significant association among the presence of replicative RNA in the heart, lung,
      and BAT, widespread antigen expression (in > or =5 tissues), and RNA viremia. Of
      these three tissues, the heart retained negative-strand RNA and viral N antigen
      the most consistently (in 25 of 26 animals). During persistence, there were two
      distinct patterns of infection: restricted versus disseminated tissue
      involvement. Mice with the restricted pattern exhibited N antigen expression in <
      or =3 tissues, an absence of viral RNA in the blood, neutralizing antibody titers
      of < or =1:1,280 (P = 0.01), and no replicative RNA in the heart, lung, or BAT.
      Those with the "disseminated" pattern showed N antigen expression in > or =5
      tissues, neutralizing antibody titers of 1:160 to 1:20,480, replicative RNA in
      the heart, lung, and BAT at a high frequency, and RNA viremia. Virus could be
      isolated consistently only from mice that demonstrated the disseminated pattern.
      The heart, lung, and BAT are important sites for the replication and maintenance
      of SN virus during persistent infection.

PMID- 12502868
TI  - Endogenous human papillomavirus E6 and E7 proteins differentially regulate
      proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells.
AB  - Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7
      proteins, and repression of HPV gene expression causes the cells to cease
      proliferation and undergo senescence. However, it is not known whether both HPV
      proteins are required to maintain the proliferative state of cervical cancer
      cells, or whether mutations that accumulate during carcinogenesis eliminate the
      need for one or the other of them. To address these questions, we used the bovine
      papillomavirus E2 protein to repress the expression of either the E6 protein or
      the E7 protein encoded by integrated HPV18 DNA in HeLa cervical carcinoma cells.
      Repression of the E7 protein activated the Rb pathway but not the p53 pathway and
      triggered senescence, whereas repression of the E6 protein activated the p53
      pathway but not the Rb pathway and triggered both senescence and apoptosis.
      Telomerase activity, cyclin-dependent kinase activity, and expression of c-myc
      were markedly inhibited by repression of either E6 or E7. These results
      demonstrate that continuous expression of both the E6 and the E7 protein is
      required for optimal proliferation of cervical carcinoma cells and that the two
      viral proteins exert distinct effects on cell survival and proliferation.
      Therefore, strategies that inhibit the expression or activity of either viral
      protein are likely to inhibit the growth of HPV-associated cancers.

PMID- 12502869
TI  - Two human immunodeficiency virus vaccinal lipopeptides follow different cross
      presentation pathways in human dendritic cells.
AB  - An efficient vaccine against human immunodeficiency virus (HIV) must induce good
      cellular immune responses. To do this, it must be processed and presented by
      dendritic cells, which are required for primary T-lymphocyte stimulation. We have
      previously shown that a model lipopeptide containing a short epitopic peptide
      from HIV-1 was endocytosed and presented in association with major
      histocompatibility complex class I molecules by human dendritic cells to specific
      CD8(+) T lymphocytes, but the cross-presentation pathway needed to be precisely
      determined. We have studied a longer lipopeptide (Pol(461-484)) and another
      lipopeptide (Nef(66-97)) currently being used in vaccine trials. Like the shorter
      lipopeptide, the rhodamine-labeled Pol(461-484) lipopeptide was internalized by
      endocytosis, as assessed by confocal microscopy. The lipopeptides were processed
      by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201
      restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope,
      respectively. Presentation of both lipopeptides was inhibited by brefeldin A.
      Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome
      specific inhibitor, but not by monensin. This shows that it gained access to the
      cytosol to be digested by the proteasome. In contrast, presentation of the Nef
      lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a
      classical inhibitor of acid-dependent endosomal enzyme activity, indicating an
      endocytic processing pathway yielding to major histocompatibility complex class I
      restricted presentation. Therefore, the two lipopeptides followed different cross
      presentation pathways, both resulting in efficient presentation to CD8(+) T
      lymphocytes.

PMID- 12502870
TI  - Development of a dual recombinant vaccine to protect small ruminants against
      peste-des-petits-ruminants virus and capripoxvirus infections.
AB  - A recombinant capripoxvirus vaccine containing a cDNA of the peste-des-petits
      ruminants virus (PPRV) fusion protein gene was constructed. A quick and efficient
      method was used to select a highly purified recombinant virus clone. A trial
      showed that a dose of this recombinant as low as 0.1 PFU protected goats against
      challenge with a virulent PPRV strain.

PMID- 12502871
TI  - Hepatitis C virus f protein is a short-lived protein associated with the
      endoplasmic reticulum.
AB  - Hepatitis C virus (HCV) F protein is a newly discovered HCV gene product that is
      expressed by translational ribosomal frameshift. Little is known about the
      biological properties of this protein. By performing pulse-chase labeling
      experiments, we demonstrate here that the F protein is a labile protein with a
      half-life of <10 min in Huh7 hepatoma cells and in vitro. The half-life of the F
      protein could be substantially increased by proteasome inhibitors, suggesting
      that the rapid degradation of the F protein is mediated by the proteasome
      pathway. Further immunofluorescence staining and subcellular fractionation
      experiments indicate that the F protein is primarily associated with the
      endoplasmic reticulum. This subcellular localization is similar to those of HCV
      core and NS5A proteins, raising the possibility that the F protein may
      participate in HCV morphogenesis or replication.

PMID- 12502872
TI  - Common sites of retroviral integration in mouse hematopoietic tumors identified
      by high-throughput, single nucleotide polymorphism-based mapping and bacterial
      artificial chromosome hybridization.
AB  - Retroviral insertional mutagenesis in mouse hematopoietic tumors provides a
      powerful cancer gene discovery tool. Here, we describe a high-throughput, single
      nucleotide polymorphism (SNP)-based method, for mapping retroviral integration
      sites cloned from mouse tumors, and a bacterial artificial chromosome (BAC)
      hybridization method, for localizing these retroviral integration sites to common
      sites of retroviral integration (CISs). Several new CISs were identified,
      including one CIS that mapped near Notch1, a gene that has been causally
      associated with human T-cell tumors. This mapping method is applicable to many
      different species, including ones where few genetic markers and little genomic
      sequence information are available. It can also be used to map endogenous
      proviruses.

PMID- 12502873
TI  - Proline 78 is crucial for human immunodeficiency virus type 1 Nef to down
      regulate class I human leukocyte antigen.
AB  - Human immunodeficiency virus type 1 Nef down-regulates human leukocyte antigen
      class I (HLA-I) in T lymphocytes, and the down-regulation involves the Nef
      proline-rich domain (PRD) containing four prolines at positions 69, 72, 75, and
      78. We used a Sendai virus vector with nef and examined regulation by Nef of HLA
      I and CD4 in suspension cultures of cells such as T lymphocytes. Analyses of a
      series of PRD substitution mutants indicated that, because the substitution of
      Pro78 with Ala abolished down-regulation of HLA-I but not of CD4, Pro78 is
      important for HLA-I down-regulation in T lymphocytes.

PMID- 12502874
TI  - Simian virus 40 sequences in human lymphoblastoid B-cell lines.
AB  - Human Epstein-Barr virus-immortalized lymphoblastoid B-cell lines tested positive
      by PCR for simian virus 40 (SV40) DNA (22 of 42 cell lines, 52.3%). B lymphocytes
      or tissues from which B-cell lines derived were also SV40 positive. In situ
      hybridization showed that SV40 DNA was present in the nucleus of a small fraction
      (1/250) of cells. SV40 T-antigen mRNA was detected by reverse transcription-PCR.
      Lymphoblastoid B-cell lines (n = 4) infected with SV40 remained SV40 positive for
      4 to 6 months. SV40-positive B-cell lines were more tumorigenic in SCID mice than
      were SV40-negative cell lines (4 of 5 [80%] SV40-positive cell lines versus 2 of
      4 [50%] SV40-negative cell lines). These results suggest that SV40 may play a
      role in the early phases of human lymphomagenesis.

PMID- 12502875
TI  - Cofactors for human immunodeficiency virus type 1 cDNA integration in vitro.
AB  - We have investigated the function of two DNA binding proteins that stimulate
      human immunodeficiency virus type 1 cDNA integration in vitro, the cellular HMGa1
      protein and the viral nucleocapsid (NC) protein. Of the three forms of NC (NCp7,
      NCp9, and NCp15), we find that NCp9 is the most effective at increasing
      integration in vitro; thus, processing of NC may potentially modulate its
      activities during infection. We also found that maximal stimulation by NCp9
      required roughly enough NC to coat the reactant DNAs whereas less HMGa1 was
      required, and the reactions displayed different optima for divalent metal
      cofactors and order of addition. These findings reveal probable distinct
      mechanisms of action in vitro.

PMID- 12502876
TI  - Recognition of native hepatitis C virus E1E2 heterodimers by a human monoclonal
      antibody.
AB  - The majority of hepatitis C virus (HCV)-infected individuals progress from acute
      to chronic disease, despite the presence of a strong humoral immune response to
      the envelope glycoproteins E1 and E2. When expressed in mammalian cells, E1 and
      E2 form both noncovalently linked E1E2 heterodimers, believed to be properly
      folded, and disulfide-linked, high-molecular-weight aggregates that are
      misfolded. Previously, we identified 10 human monoclonal antibodies (HMAbs) that
      bind E2 glycoproteins from different genotypes. Here we demonstrate that one of
      these HMAbs, CBH-2, is unique in its ability to distinguish between properly
      folded and misfolded envelope proteins. This HMAb recognizes HCV-E2 only when
      complexed with E1. The E1E2 complexes recognized by CBH-2 are noncovalently
      linked heterodimers and not misfolded disulfide-linked, high-molecular-weight
      aggregates. The E1E2 heterodimers seen by CBH-2 no longer associate with the
      endoplasmic reticulum chaperone calnexin and are likely to represent the
      prebudding form of the HCV virion.

PMID- 12502877
TI  - Baseline susceptibility of primary human immunodeficiency virus type 1 to entry
      inhibitors.
AB  - Human immunodeficiency virus type 1 plasma viruses from 29 entry inhibitor-naive
      patients were characterized for their susceptibilities to T-20, AMD3100, and
      RANTES. A strikingly wide range of susceptibilities to T-20 was observed that was
      influenced by coreceptor usage but not by the susceptibilities of the viruses to
      inhibitors that target the chemokine receptors or by polymorphisms in the gp41 N
      helix.

PMID- 12502878
TI  - The high-risk human papillomavirus type 16 E6 counters the GAP function of E6TP1
      toward small Rap G proteins.
AB  - We have recently identified E6TP1 (E6-targeted protein 1) as a novel high-risk
      human papillomavirus type 16 (HPV16) E6-binding protein. Importantly, mutational
      analysis of E6 revealed a strong correlation between the transforming activity
      and its abilities to bind and target E6TP1 for ubiquitin-mediated degradation. As
      a region within E6TP1 has high homology with GAP domains of known and putative
      Rap GTPase-activating proteins (GAPs), these results raised the possibility that
      HPV E6 may alter the Rap small-G-protein signaling pathway. Using two different
      approaches, we now demonstrate that human E6TP1 exhibits GAP activity for Rap1
      and Rap2, confirming recent findings that a closely related rat homologue
      exhibits Rap-specific GAP activity. Using mutational analysis, we localize the
      GAP activity to residues 240 to 945 of E6TP1. Significantly, we demonstrate that
      coexpression of HPV16 E6, by promoting the degradation of E6TP1, enhances the GTP
      loading of Rap. These results support a role of Rap small-G-protein pathway in E6
      mediated oncogenesis.

PMID- 12502879
TI  - Novel viral disease control strategy: adenovirus expressing alpha interferon
      rapidly protects swine from foot-and-mouth disease.
AB  - We have previously shown that replication of foot-and-mouth disease virus (FMDV)
      is highly sensitive to alpha/beta interferon (IFN-alpha/beta). In the present
      study, we constructed recombinant, replication-defective human adenovirus type 5
      vectors containing either porcine IFN-alpha or IFN-beta (Ad5-pIFNalpha or Ad5
      pIFNbeta). We demonstrated that cells infected with these viruses express high
      levels of biologically active IFN. Swine inoculated with 10(9) PFU of a control
      Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed
      typical signs of foot-and-mouth disease (FMD), including fever, vesicular
      lesions, and viremia. In contrast, swine inoculated with 10(9) PFU of Ad5
      pIFNalpha were completely protected when challenged 24 h later with FMDV. These
      animals showed no clinical signs of FMD and no viremia and did not develop
      antibodies against viral nonstructural proteins, suggesting that complete
      protection from infection was achieved.

PMID- 12502880
TI  - Amino acid residues 88 and 89 in the central hydrophilic region of human
      immunodeficiency virus type 1 Vif are critical for viral infectivity by enhancing
      the steady-state expression of Vif.
AB  - A hydrophilic region consisting of strikingly clustered charged amino acids is
      present at the center of human immunodeficiency virus type 1 (HIV-1) Vif. In this
      study, the role for this central hydrophilic region (E(88)WRKKR(93)) in the virus
      replication in nonpermissive H9 cells was investigated by extensive deletion and
      substitution analysis. A total of 31 mutants were constructed. Deletion of the
      E(88) or W(89) residue alone abolished viral infectivity in H9 cells and impaired
      virus replication in primary macrophage cultures. Substitution analysis indicated
      that the hydrophilicity and charge of the central region are insignificant for
      the function of Vif. Of the 16 substitution mutants, 3 mutants with substitution
      of E(88) and W(89) with an A residue did not grow in H9 cells. Upon transfection,
      four mutants (i.e., two mutants with deletion of E(88) or W(89); a mutant with
      substitution of E(88) and W(89) with A; and a mutant with substitution of E(88),
      W(89), and R(90) with A) were found to express Vif at a very reduced level
      relative to that by the wild-type clone. These results have thus demonstrated
      that amino acid residues 88 and 89 of Vif are critical for the replication of HIV
      1 in target cells by enhancing the steady-state expression of Vif. In addition,
      E(88) and W(89) residues were found to be extremely conserved among the Vif
      proteins of naturally occurring HIV-1 field isolates as well as those of
      laboratory HIV-1 strains.

PMID- 12502881
TI  - Transcription initiation activity of adenovirus left-end sequence in adenovirus
      vectors with e1 deleted.
AB  - We analyzed the transcription initiation activity of the left-end sequence (first
      342 bp) of the adenovirus genome in the context of an adenovirus vector with E1
      deleted in in vitro and in vivo gene transfer models. While nucleotide sequences
      1 to 190 and 1 to 342 showed strong activity in three out of three lung cancer
      cell lines, nucleotide sequence 1 to 103 showed limited activity in H358, cells
      which show characteristics of type 2 alveolar cells. In vivo, the transcription
      initiation activities of nucleotide sequence 1 to 103 in the liver and the lung
      were minimal, while nucleotide sequences 1 to 190 and 1 to 342 showed strong
      activity comparable to that of the cytomegalovirus promoter. Further
      understanding of the transcription initiation activity of the left-end sequence
      of the adenovirus genome should lead to optimization of adenovirus vectors.

PMID- 12502882
TI  - Hantavirus pulmonary syndrome-associated hantaviruses contain conserved and
      functional ITAM signaling elements.
AB  - Hantaviruses infect human endothelial and immune cells, causing two human
      diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary
      syndrome (HPS). We have identified key signaling elements termed immunoreceptor
      tyrosine-based activation motifs (ITAMs) within the G1 cytoplasmic tail of all
      HPS-causing hantaviruses. ITAMs direct receptor signaling within immune and
      endothelial cells and the presence of ITAMs in all HPS-causing hantaviruses
      provides a means for altering normal cellular responses which maintain vascular
      integrity. The NY-1 G1 ITAM was shown to coprecipitate a complex of
      phosphoproteins from cells, and the G1 ITAM is a substrate for the Src family
      kinase Fyn. The hantavirus ITAM coprecipitated Lyn, Syk, and ZAP-70 kinases from
      T or B cells, while mutagenesis of the ITAM abolished these interactions. In
      addition, G1 ITAM tyrosines directed intracellular interactions with Syk by
      mammalian two-hybrid analysis. These findings demonstrate that G1 ITAMs bind key
      cellular kinases that regulate immune and endothelial cell functions. There is
      currently no means for establishing the role of the G1 ITAM in hantavirus
      pathogenesis. However, the conservation of G1 ITAMs in all HPS-causing
      hantaviruses and the role of these signaling elements in immune and endothelial
      cells suggest that functional G1 ITAMs are likely to dysregulate normal immune
      and endothelial cell responses and contribute to hantavirus pathogenesis.

PMID- 12502883
TI  - Yellow fever virus replicons as an expression system for hepatitis C virus
      structural proteins.
AB  - Chimeric yellow fever virus (YF) RNAs were constructed in which the YF structural
      genes were replaced by the hepatitis C virus (HCV) structural genes or fusions
      between the YF and HCV structural genes. Interestingly, RNA replication required
      nucleotide complementarity between the 3'-located conserved sequence 1 and an RNA
      sequence located in the 5' end of the YF capsid sequence. The (chimeric-)HCV
      structural proteins were efficiently expressed and processed, and the native
      E1/E2 heterodimer was formed. However, no indication for the production of HCV
      like particles was obtained.

PMID- 12502884
TI  - Valency of antibody binding to enveloped virus particles as determined by surface
      plasmon resonance.
AB  - A simple method is described for determining the valency of binding of
      immunoglobulin G to immobilized influenza A virus. Where there is a free Fab arm
      (monovalent binding), a second virus particle is captured. This is detected by
      surface plasmon resonance. The methodology should be applicable to all enveloped
      and nonenveloped viruses.

PMID- 12502885
TI  - A live, attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide
      deletion in the 3' untranslated region is highly attenuated and immunogenic in
      monkeys.
AB  - The Delta30 deletion mutation, which was originally created in dengue virus type
      4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region
      (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus
      type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus
      monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate.
      rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described
      vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and
      both vaccines were highly protective against challenge with wt DEN1. Both
      rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However,
      neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following
      intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability
      of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a
      tetravalent DEN vaccine could be generated by introduction of the Delta30
      mutation into wt DEN viruses belonging to each of the four serotypes.

PMID- 12502886
TI  - Live cell imaging: approaches for studying protein dynamics in living cells.
AB  - In the last decade, the long-standing biologist's dream of seeing the molecular
      events within the living cell came true. This technological achievement is
      largely due to the development of fluorescence microscopy technologies and the
      advent of green fluorescent protein as a fluorescent probe. Such imaging
      technologies allowed us to determine the subcellular localization, mobility and
      transport pathways of specific proteins and even visualize protein-protein
      interactions of single molecules in living cells. Direct observation of such
      molecular dynamics can provide important information about cellular events that
      cannot be obtained by other methods. Thus, imaging of protein dynamics in living
      cells becomes an important tool for cell biology to study molecular and cellular
      functions. In this special issue of review articles, we review various imaging
      technologies of microscope hardware and fluorescent probes useful for cell
      biologists, with a focus on recent development of live cell imaging.

PMID- 12502887
TI  - Live cell imaging using wide-field microscopy and deconvolution.
AB  - The use of fluorescence imaging methods, most recently based on fluorescent
      protein technology, and the availability of high quality fluorescence imaging
      systems have driven a revolution in cell and molecular biology. Live cell
      imaging, especially using fluorescence, is now used in a wide variety of assays
      in academic and commercial laboratories. The use of this technology requires
      particular attention to be paid to cell engineering, the design of the image
      acquisition system, the imaging protocol, and subsequent processing and analytic
      methods. In this review, we discuss each of these steps, highlighting practical
      techniques developed by us and others.

PMID- 12502888
TI  - Green fluorescent protein-like proteins in reef Anthozoa animals.
AB  - Green fluorescent protein (GFP) from the bioluminescent jellyfish Aequorea
      victoria has become an important tool in molecular and cellular biology as a
      transcriptional reporter, fusion tag, and biosensor. Most significantly, it
      encodes a chromophore intrinsically within its protein sequence, obviating the
      need for external substrates or cofactors and enabling the genetic encoding of
      strong fluorescence. Mutagenesis studies have generated GFP variants with new
      colors, improved fluorescence and other biochemical properties. In parallel, GFPs
      and GFP-like molecules have been cloned from other organisms, including the
      bioluminescent sea pansy Renilla reniformis and other non-bioluminescent Anthozoa
      animals. In the jellyfish and sea pansy, the GFPs are coupled to their
      chemoluminescence. Instead of emitting the blue light generated by aequorin and
      luciferase, the GFPs absorb their energy of primary emission and emit green
      light, which travels farther in the sea. In contrast, GFP-like proteins in reef
      Anthozoa are thought to play a role in photoprotection of their symbiotic
      zooxanthellae in shallow water; they transform absorbed UV radiation contained in
      sunlight into longer fluorescence wavelengths (Salih, A., Larkum, A., Cox, G.,
      Kuhl, M., and Hoegh-Guldberg, O. 2000. Nature, 408: 850-853). In this review, I
      will describe both the biological and practical aspects of Anthozoan GFP-like
      proteins, many of which will be greatly improved in utility and commercially
      available before long. The ubiquity of these molecular tools makes it important
      to appreciate the interplay between sunlight and GFP-like proteins of Anthozoan
      animals, and to consider the optimal use of these unique proteins in biological
      studies.

PMID- 12502889
TI  - Spinning-disk confocal microscopy -- a cutting-edge tool for imaging of membrane
      traffic.
AB  - Confocal laser scanning microscopy is experiencing a revolution in speed from the
      world of seconds to that of milliseconds. The spinning Nipkow disk method with
      microlenses has made this remarkable innovation possible. In combination with the
      ultrahigh-sensitivity, high-speed and high-resolution camera system based on
      avalanche multiplication of photoconduction, we are now able to observe the
      extremely dynamic movement of small vesicles in living cells in real time.

PMID- 12502890
TI  - Total internal reflection fluorescence microscopy for single-molecule imaging in
      living cells.
AB  - Marvelous background rejection in total internal reflection fluorescence
      microscopy (TIR-FM) has made it possible to visualize single-fluorophores in
      living cells. Cell signaling proteins including peptide hormones, membrane
      receptors, small G proteins, cytoplasmic kinases as well as small signaling
      compounds have been conjugated with single chemical fluorophore or tagged with
      green fluorescent proteins and visualized in living cells. In this review, the
      reasons why single-molecule analysis is essential for studies of intracellular
      protein systems such as cell signaling system are discussed, the instrumentation
      of TIR-FM for single-molecule imaging in living cells is explained, and how
      single molecule visualization has been used in cell biology is illustrated by way
      of two examples: signaling of epidermal growth factor in mammalian cells and
      chemotaxis of Dictyostelium amoeba along a cAMP gradient. Single-molecule
      analysis is an ideal method to quantify the parameters of reaction dynamics and
      kinetics of unitary processes within intracellular protein systems. Knowledge of
      these parameters is crucial for the understanding of the molecular mechanisms
      underlying intracellular events, thus single-molecule imaging in living cells
      will be one of the major technologies in cellular nanobiology.

PMID- 12502891
TI  - Multispectral imaging fluorescence microscopy for living cells.
AB  - Multispectral imaging technologies have been widely used in fields of astronomy
      and remote sensing. Interdisciplinary approaches developed in, for example, the
      National Aeronautics and Space Administration (NASA, USA), the Jet Propulsion
      Laboratory (JPL, USA), or the Communications Research Laboratory (CRL, Japan)
      have extended the application areas of these technologies from planetary systems
      to cellular systems. Here we overview multispectral imaging systems that have
      been devised for microscope applications. We introduce these systems with
      particular interest in live cell imaging. Finally we demonstrate examples of
      spectral imaging of living cells using commercially available systems with no
      need for user engineering.

PMID- 12502892
TI  - Immunolocalization of caveolin-1 and caveolin-3 in monkey skeletal, cardiac and
      uterine smooth muscles.
AB  - Caveolin, a 20-24 kDa integral membrane protein, is a principal component of
      caveolar domains. Caveolin-1 is expressed predominantly in endothelial cells,
      fibroblasts, and adipocytes, while the expression of caveolin-3 is confined to
      muscle cells. However, their localization in various muscles has not been well
      documented. Using double-immunofluorescence labeling and confocal laser
      microscopy, we examined the localization of caveolins-1 and 3 in adult monkey
      skeletal, cardiac and uterine smooth muscles and the co-immunolocalization of
      these caveolins with dystrophin, which is a product of the Duchenne muscular
      dystrophy gene. In the skeletal muscle tissue, caveolin-3 was localized along the
      sarcolemma except for the transverse tubules, and co-immunolocalized with
      dystrophin, whereas caveolin-1 was absent except in the blood vessels of the
      muscle tissue. In cardiac muscle cells, caveolins-1 and -3 and dystrophin were co
      immunolocalized on the sarcolemma and transverse tubules. In uterine smooth
      muscle cells, caveolin-1, but not caveolin-3, was co-immunolocalized with
      dystrophin on the sarcolemma.

PMID- 12502893
TI  - Characterization of Arp2/3 complex in chicken tissues.
AB  - Arp2/3 protein complex consists of seven subunits (Arp2, Arp3, p41-Arc, p34-Arc,
      p21-Arc, p20-Arc and p16-Arc) in apparent 1:1 stoichiometry. This complex has
      been shown to promote the formation of Y-branch structures of F-actin in cultured
      cells. We generated specific antibodies against chicken Arp2, Arp3, and p34-Arc
      to analyze the distribution of these subunits in chicken tissues. In whole
      samples of brain and gizzard, antibodies against each recombinant protein reacted
      with single bands of predicted molecular mass based on their cDNA sequences of
      the antigens. Anti-p34-Arc antibody detected at least two neighboring spots in 2D
      PAGE, which might suggest the existence of isoforms or modified forms. Arp2/3
      complex bound to an F-actin affinity column from gizzard extract. However, Arp2/3
      complex did not tightly bind major actin cytoskeleton because the complex was
      extracted easily when gizzard smooth muscle was homogenized in PBS. Immunoblot
      analysis of various tissues revealed that the amounts of Arp2/3 subunits were
      lower in striated muscle than in non-muscle and smooth muscle tissues. Amounts
      and ratio of the three subunits varied in tissues, as estimated by quantitative
      immunoblotting. With immunofluorescence microscopy, we also observed localization
      of Arp3 and p34-Arc in frozen sections of gizzard with different staining
      patterns around blood vessels. These results suggest that the Arp2/3 complex
      exists also in places where rapid actin polymerization does not occur, and that a
      part of the subunits may exist in different forms from the complex containing the
      seven subunits in some tissues.

PMID- 12502894
TI  - Immunosuppressant FK506 induces sustained activation of MAP kinase and promotes
      neurite outgrowth in PC12 mutant cells incapable of differentiating.
AB  - During the continuous culturing of neural PC12 cells, a drug hypersensitive PC12
      mutant cell line (PC12m3) was obtained, which demonstrated high neurite outgrowth
      when stimulated by various drugs. When the immunosuppressant drug FK506 and nerve
      growth factor (NGF) were introduced to the PC12m3 cells, the frequency of neurite
      outgrowth increased approximately 40-fold for NGF alone. However, the effect of
      FK506 on neuritogenesis in PC12 parental and drug insensitive PC12m1 mutant cells
      was much lower than in PC12m3 cells. The sustained activation of mitogen
      activated protein (MAP) kinase plays an important role in neurite outgrowth of
      PC12 cells. Interestingly, the drug hypersensitive PC12m3 cells exhibited the
      sustained activation of MAP kinase with FK506 in comparison to low or no
      activities in PC12 parental or drug insensitive PC12m1 cells. These results
      indicate that PC12m3 cells have a novel FK506-induced MAP kinase pathway for
      neuritogenesis.

PMID- 12502895
TI  - Architectural changes in the developing human brain based on the matrix cell
      theory.
AB  - Architectural changes in the developing human brain are discussed based on the
      matrix cell theory. Neural stem cells/matrix cells with self-renewing ability and
      multipotency exist in the developing human brain in vivo. The brain development
      is divided into three stages and the cell differentiation is time regulated.
      Immunohistochemical distribution of various markers for brain development is
      summarized and categorized along with differentiation lineages. Particularly, the
      existence of glial fibrillary acidic protein is re-evaluated in the developing
      human brain. The commonly used terms and concepts "radial glial fiber" or
      "subventricular zone" are also re-evaluated.

PMID- 12502896
TI  - An examination of different fetal specific antibodies and magnetic activated cell
      sorting for the enrichment of fetal erythroblasts from maternal blood.
AB  - The aim of the present study was to compare the rates of fetal cells obtained
      after separation from maternal blood by magnetic activated cell sorting (MACS)
      using different fetal specific antibodies, and to evaluate the potential role of
      this method in the prenatal diagnosis of fetal trisomies. Peripheral blood
      samples were obtained from 42 women carrying chromosomally normal fetuses and
      from 4 women with aneuploid fetuses (2 cases of 47,XX,+18 and 2 of 47,XY,+21) at
      9-20 weeks of gestation. After fetal cells were enriched by MACS with three
      different monoclonal antibodies (GPA, CD71, CD14), fluorescence in situ
      hybridization (FISH) with chromosome X, and Y-specific probes was performed to
      detect the rates of fetal cells in the samples sorted. FISH with chromosome 13-,
      18-, and 21-specific probes was carried out to compare proportions of cells with
      three-signal nuclei in chromosomally normal and abnormal groups. In male infants,
      X- and Y-positive cells were detected in 80%, 73.3%, and 66.6% of samples after
      the separation by antibodies CD14, GPA, and CD71, respectively. The percentage of
      nuclei with three signals was increased in pregnancies with trisomy, ranging
      between 2% and 5.18%. Pregnancies with normal fetuses showed 0 to 3.7% of nuclei
      with three signals. The data demonstrate that fetal cell detection varies
      depending on the antibodies used for cell sorting. This study provides further
      evidence on the feasibility of screening for fetal chromosomal abnormalities by
      enriching maternal blood for fetal cells and using FISH.

PMID- 12502897
TI  - Immunological evaluation and clinical aspects of children with congenital
      cytomegalovirus infection.
AB  - To determine the ability of immunological response to human cytomegalovirus
      (CMV), the flow cytometric assay was evaluated as a tool for real-time monitoring
      of specific cellular immunity in children with congenital CMV infection.
      Longitudinal cohort study of 2 children with asymptomatic and 2 with symptomatic
      congenital CMV infection evaluated at birth and followed up with serial age
      appropriate neurodevelopmental testing. Frequencies of CMV-specific CD4 (+) T
      cell in these children were detected by intracellular cytokines (ICC), interferon
      (IFN)-gamma and tumor necrosis factor (TNF)-alpha, staining. Findings detected by
      CT and MRI were the most sensitive predictor for neurodevelopmental prognosis.
      Frequencies of CMV-specific CD4(+) T cells detected by ICC, both IFN-gamma and
      TNF-alpha, were higher in 2 children with symptomatic congenital CMV infection
      than those in 2 children with asymptomatic congenital infection. Frequencies of
      CMV-specific CD4(+) T cells in 2 children with symptomatic congenital infection
      were significantly higher than those in 6 healthy children of 1 to 5-years of age
      with serum anti-CMV IgG antibody without serum anti-CMV IgM antibody and viral
      excretion in to urine (p < 0.01). The ICC assay reflects immunological activity
      against CMV infection in children with asymptomatic or symptomatic congenial
      infection. Categorizing findings obtained by the ICC assay may helps to determine
      the prognosis of children with congenital CMV infection.

PMID- 12502898
TI  - New behavioral mutant rat exhibiting circling behavior (clx) controlled by a sex
      linked recessive gene.
AB  - A male rat showing intermittent circling behavior was discovered among the
      Jcl:Wistar rats in our laboratories, and among its backcross offspring
      individuals showing the same behavior were found. The abnormalities in these
      animals were characterized by intermittent circling behavior (walking and/or
      running in circles) and head tossing with the neck twisted. No abnormalities were
      observed in fertility, delivery or pup mortality. The results of mating
      experiments indicated that the circling behavior phenotype is controlled by a
      single sex-linked recessive gene, and the mutant was named "circling behavior
      linked to X-chromosome (gene symbol: clx)." This circling behavior mutant is
      considered to be different from the previously reported mutants, the behavior in
      all of which has been found to be autosomally inherited. Sib-mating is continuing
      to produce an inbred strain with this newly discovered circling behavior mutant
      gene.

PMID- 12502899
TI  - Historical control data on reproductive abilities and incidences of spontaneous
      fetal malformations in Wistar Hannover GALAS rats.
AB  - Wistar Hannover rats, which have recently been introduced into Japan, are
      expected to be used in reproductive and developmental toxicity studies, yet the
      accumulation of background data is insufficient. This paper describes our
      historical data on the reproductive ability of this strain of rat. Three lots of
      sexually matured females (40 each) were received from CLEA JAPAN, Inc. with males
      of the same strain (30 or 36 each) and mated. A total of 47 dams were killed on
      gestation day 20 to examine their fetuses. The remaining 71 pregnant females were
      allowed to deliver spontaneously and observed for common reproductive parameters.
      The mating and fertility indices of females were both 99.2%. Overall mean numbers
      of implants and live fetuses at cesarean sectioning were 12.5 and 11.5,
      respectively. Fetal resorptions and deaths occurred at an incidence of 8.6%.
      Morphological examinations of fetuses revealed low incidences of spontaneous
      malformations (each one case of double aortic arch and absent cervical vertebral
      arch) and a variety of common variations. The followings are overall means of
      major reproductive parameters obtained from females with live birth: no. of
      implants, 12.5; no. of pups delivered, 11.8; viability index of pups at birth,
      99.8%; and days of age at sexual maturation (vaginal opening and preputial
      separation), 30.3 and 42.8, respectively. Our present observations confirmed a
      minimal deviation among 3 lots of animals in terms of reproductive abilities.
      These results suggest that this strain of rat can be used in reproductive and
      developmental toxicity studies, although the sensitivity to toxicants remains to
      be elucidated.

PMID- 12502901
TI  - The effect of the small and unstable autologous osteochondral graft on repairing
      the full-thickness large articular cartilage defect in a rabbit model.
AB  - We have investigated the effect of the insufficient autologous osteochondral
      graft on healing of the large articular cartilage defect using a rabbit model. An
      osteochondral defect, 7 mm in diameter, was made on the patellar groove of the
      femoral condyle and repaired with two surgical procedures: Group I, the
      osteochondral fragment as half as the defect was grafted. The graft was unstable
      and the size of the graft was smaller than the defect. This is a model of the
      insufficient autologous osteochondral graft to the large articular cartilage
      defect; Group II, the defect was left empty. At 2, 4, 12, and 24 weeks after the
      surgery, the specimens were analyzed macroscopically and histologically. To
      evaluate the microscopic morphology, a histologic grading scale composed of 5
      categories was used. In Group I, although the graft sank a little, a grafted
      cartilage survived and the reparative fibrous tissue filled the defect covering
      implanted cartilage. In contrast, in Group II, the defect was only partially
      covered by fibrocartilaginous tissue with a faintly staining matrix. Throughout
      the entire observed periods, the scores of the repaired cartilage in Group I are
      significantly higher than those in Group II. Even the half size of osteochondral
      graft has an effect to reduce the size of the cartilage defect such as the spacer
      and leads to better healing compared to the cartilage defect untreated. In case
      that it is hard to transplant an optimal osteochondral graft because of large
      cartilage lesion, even the small and unstable osteochondral plug should be
      transplanted.

PMID- 12502902
TI  - In vivo administration of glucosamine inhibited phosphatidylinositol 3-kinase
      activity without affecting tyrosine phosphorylation of the insulin receptor or
      insulin receptor substrate in rat adipocytes.
AB  - We examined insulin signaling in rat epididymal adipocytes which developed
      insulin resistance by the in vivo infusion of glucosamine. Insulin-stimulated 2
      deoxyglucose uptake into the adipocytes isolated from rats which were infused
      glucosamine for 4 hours was diminished by 26%. To analyze insulin signaling in
      adipocytes, the epididymal fat tissues were harvested 5 minutes after insulin
      administration (10U/kg), which was administered immediately after glucosamine
      infusion. Glucosamine had no effect on the insulin-stimulated tyrosine
      phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1.
      Glucosamine infusion decreased insulin-stimulated phosphatidylinositol (PI) 3
      kinase activity by 66%. Glucosamine infusion also inhibited insulin-stimulated PI
      3-kinase activity associated with IRS-1, 2, 3 by 30%, 43%, and 44%, respectively.
      There was no difference in the association of the 85kDa subunit of PI 3-kinase
      with the IRS-1 and IRS-2 protein. PI 3-kinase activity in adipocytes from rats
      treated with glucosamine that were administered platelet derived growth factor
      (3microg/kg) for 5 minutes was also reduced by 39%. When we measured the kinase
      activity of protein kinase C (PKC) lamda, which is the downstream effector of PI
      3-kinase in isolated adipocytes, we found that glucosamine inhibited insulin
      stimulated PKClamda kinase activity by 33%. These results suggest that
      glucosamine infusion contributes to the development of insulin resistance by
      mainly modulating the PI 3-kinase molecules.

PMID- 12502903
TI  - Titanium-alloy particles induced cyclooxygenase-2 in human macrophage-like cells
      in vitro.
AB  - Prostaglandin E2 (PGE2) has been reported to be an important mediator in aseptic
      loosening and/or periprosthetic osteolysis in total joint arthroplasties.
      Previous studies have reported that human macrophages stimulated with particles
      in vitro release PGE2. However, they have not shown the expression of
      cyclooxygenases (COX) which are rate-limiting enzymes of PGE2 synthesis. We
      hypothesized that PGE2 production by activated macrophages is dependent upon the
      induction of COX-2, not upon the constitutive isozyme, COX-1. When we evaluated
      the expression of COX-1 and COX-2 in titanium-alloy particle-stimulated human
      macrophages, the expression of COX-2 mRNA was up-regulated by the particles, on
      the other hand, the expression of COX-1 mRNA was not affected. In addition, NS
      398, a COX-2 inhibitor drastically suppressed up-regulated PGE2 production by the
      particles. These results provide strong evidence that PGE2 production by particle
      stimulated macrophages is dependent upon the induction of COX-2, not COX-1.

PMID- 12502904
TI  - Gly71Arg mutation of the bilirubin UDP-glucuronosyltransferase 1A1 gene is
      associated with neonatal hyperbilirubinemia in the Japanese population.
AB  - The serum bilirubin level of Japanese newborn infants in their first few days is
      significantly higher than that in Caucasian newborn infants, suggesting that
      there might be genetic risk factors for the development of neonatal
      hyperbilirubinemia in the Japanese population. Recently, it has been reported
      that a variant TATA box in the promoter region of the bilirubin UDP
      glucuronosyltransferase 1 (UGT1A1) gene is associated with the development of
      neonatal hyperbilirubinemia. This finding led us to the idea that a mutation,
      glycine to arginine at codon 71 (G71R), in the coding region of the UGT1A1 gene
      can cause neonatal hyperbilirubinemia. In this study, we determined the genotypic
      distribution of the G71R mutation in 72 Japanese newborn infants: 23 infants with
      hyperbilirubinemia and 49 infants without hyperbilirubinemia. In the
      hyperbilirubinemia group, 15 of 23 newborn infants had the G71R mutation (3
      homozygotes and 12 heterozygotes), whereas in the non-hyperbilirubinemia group 16
      of 49 newborn infants had the G71R mutation (1 homozygote and 15 heterozygotes).
      Therefore, the G71R mutation was present significantly more frequently in the
      hyperbilirubinemia group than in the non-hyperbilirubinemia group. This finding
      strongly suggests that the presence of the G71R mutation contributes to the
      development of neonatal hyperbilirubinemia in the Japanese population.

PMID- 12502905
TI  - Pulmonary dirofilariasis--clinicopathological study.
AB  - Pulmonary dirofilariasis (PD), caused by Dirofilaria immitis (D. immitis), the
      dog heartworm, is not common in humans, though we recently encountered 4 cases.
      Chest X-ray images from annual health examinations showed a single spherical
      nodule in the inferior or middle portion of the right lung in each patient. None
      of the patients showed any clinical symptoms and had no contact with dogs.
      Hematological results in 3 of the cases were within normal limits, while mild
      eosinophilia was found in one. Serological tests for the Anti-Dirofilaria
      antibodies were not performed. There were no characteristic clinical
      manifestation of PD in any of the patients, however, we consider it important to
      keep a diagnosis of PD in mind, when we experienced these cases, they present no
      characteristic clinical manifestations. Pathologically, macroscopic findings
      showed well-circumscribed nodules that were round peripheral lesions in lungs.
      Histological results revealed coagulation necrosis with fibrosis and granulation
      in the nodule edge, which contained inflammatory cells. By means of silver
      staining, the worm structures in the nodules could be identified well, and the
      quadrant cells in the sections were numbered about 30. Immunohistochemically, the
      somatic muscle tissues were stained with anti-Dirofilaria antibody. These
      findings indicated that the pulmonary lesions in all 4 cases were due to D.
      immitis.

PMID- 12502906
TI  - A voltage-gated H+ channel is a powerful mechanism for pH homeostasis in murine
      osteoclasts.
AB  - Osteoclasts secrete a large amount of proton (H+) ions and proteolytic enzymes
      into bone resorption pit to degrade bone matrix. In addition to H+ pumps and
      exchangers, voltage-gated H+ channels, which are H+ conductive pathways, are
      expressed in osteoclasts. H+ channels are distinct in their strong H+ extrusion
      ability, but the functional role is not clear. This is the first study of H+
      channels in murine osteoclasts generated from mononuclear precursors in the
      presence of a soluble form of receptor activator of nuclear factor kappa B ligand
      (RANKL) and macrophage colony stimulating factor (M-CSF). The H+ channel was
      characterized by voltage- and pH-dependent activation, slow activation kinetics,
      and outward rectification. The reversal potential (Vrev) was shifted to more
      positive potentials by decreasing the pH gradient across the plasma membrane
      (deltapH). Employing Vrev as a real time monitor of pH in clamped cells, it is
      revealed that the H+ channel activation could decrease deltapH by approximately
      0.43 unit/s. Decline in the current during prolonged depolarizations was
      accompanied by a positive shift in Vrev. This implies that the H+ channel
      activity is auto-regulated by sensing deltapH, to compensate for pH imbalance.
      The H+ current-density in cells with 36 nuclei was significantly smaller than
      that in cells with < or =5 nuclei, although the activation rate was unaltered.
      Thus, the H+ channel activity may alter during osteoclastogenesis. These data
      suggest the H+ channel is a powerful mechanism for pH homeostasis of osteoclasts
      that are exposed to drastic change in pH environments during the bone resorption
      cycle.

PMID- 12502907
TI  - Data-driven clinical care.

PMID- 12502909
TI  - Cardiovascular physiology-changes with aging.
AB  - With aging there are changes in the cardiovascular system, which result in
      alterations in cardiovascular physiology. The changes in cardiovascular
      physiology must be differentiated from the effects of pathology, such as coronary
      artery disease, that occur with increasing frequency as age increases. The
      changes with age occur in everyone but not necessarily at the same rate,
      therefore accounting for the difference seen in some people between chronologic
      age and physiologic age. The changes in the cardiovascular system associated with
      aging are a decrease in elasticity and an increase in stiffness of the arterial
      system. This results in increased afterload on the left ventricle, an increase in
      systolic blood pressure, and left ventricular hypertrophy, as well as other
      changes in the left ventricular wall that prolong relaxation of the left
      ventricle in diastole. There is a dropout of atrial pacemaker cells resulting in
      a decrease in intrinsic heart rate. With fibrosis of the cardiac skeleton there
      is calcification at the base of the aortic valve and damage to the His bundle as
      it perforates the right fibrous trigone. Finally there is decreased
      responsiveness to beta adrenergic receptor stimulation, a decreased reactivity to
      baroreceptors and chemoreceptors, and an increase in circulating catecholamines.
      These changes set the stage for isolated systolic hypertension, diastolic
      dysfunction and heart failure, atrioventricular conduction defects, and aortic
      valve calcification, all diseases seen in the elderly.

PMID- 12502910
TI  - Outcomes of treating hypertension in the elderly: a short commentary on current
      issues.
AB  - Because treating hypertension in the elderly so effectively reduces major
      cardiovascular events, it is vital to diagnose this very common condition early.
      Much of the hypertension that occurs with aging results from stiffening of the
      major capacitance arteries, typically marked by high systolic and low diastolic
      blood pressures. Pulse pressure, derived by subtracting diastolic from systolic
      values, is a useful index of stiffness, but new noninvasive techniques for
      measurement of arterial compliance have shown that blood pressures cannot
      reliably predict the state of the arteries in older people. The Systolic
      Hypertension in the Elderly Program (SHEP) and the Systolic Hypertension in
      Europe (Syst-Eur) trial demonstrated that treating hypertension in the elderly
      with diuretics or calcium channel blockers reduces strokes and cardiac events;
      these results are also clearly evident in high-risk groups like diabetics.
      Further analysis of Syst-Eur has suggested that a calcium channel blocker reduces
      new-onset dementia, while follow-up data from SHEP indicate that a diuretic
      provides survival and stroke benefits in obese or overweight elderly
      hypertensives, but not in the lean. In general, comparisons of antihypertensive
      agents, including diuretics, beta blockers, angiotensin-converting enzyme
      inhibitors, and calcium channel blockers have found similar clinical end point
      effects. But recently, the Losartan Intervention For End Point Reduction in
      Hypertension (LIFE) study, performed in patients (average age, 67) with left
      ventricular hypertrophy and predominant systolic hypertension, showed that the
      angiotensin receptor blocker losartan was significantly more effective than the
      beta blocker atenolol in reducing such key outcomes as strokes and new-onset
      diabetes. Even so, careful but effective control of blood pressure in elderly
      patients, including those over age 80, still remains a critical factor in
      preventing major cardiovascular events.

PMID- 12502911
TI  - Heart failure in the elderly: strategies to optimize outpatient control and
      reduce hospitalizations.
AB  - Heart failure is a disorder that disproportionately affects the elderly, and over
      50% of heart failure hospitalizations in the United States occur in persons over
      75 years of age. Moreover, despite recent advances in heart failure therapy,
      optimal treatment of elderly patients remains undefined. In addition, heart
      failure management in older persons is often complicated by the presence of
      multiple comorbid conditions, polypharmacy, psychosocial and behavioral concerns,
      dietary issues, and economic considerations. As a result, management of heart
      failure in the elderly requires a coordinated, multidisciplinary approach, and a
      series of recent studies have documented the efficacy of heart failure disease
      management programs in reducing readmissions, enhancing medication and dietary
      compliance, and lowering cost of care. Ongoing studies will provide insights into
      the feasibility and effectiveness of implementing heart failure disease
      management programs on a population-wide basis, and on the effects of such
      programs on long-term clinical outcomes and costs.

PMID- 12502912
TI  - Noninvasive cardiac testing in the geriatric patient.
AB  - The use and interpretation of noninvasive cardiac testing in the elderly may
      differ from that in younger patients due to changes in disease prevalence, normal
      values, comorbidities, or patient and physician preferences. This paper reviews
      the experience with several commonly used noninvasive tests such as
      electrocardiography, exercise testing, and stress imaging with echocardiography
      or with scintigraphy in geriatric patients. Most commonly used noninvasive tests
      remain feasible and safe. Data suggest that exercise stress testing is feasible
      in many elderly patients with a good safety profile and should be considered as a
      first-line test due to the extra information provided by the duration and
      hemodynamic response to exercise. Adjunctive imaging may be particularly helpful
      when the electrocardiogram is uninterpretable or suspect due to underlying
      baseline abnormalities or when determining the extent or distribution of ischemia
      is felt to be important.

PMID- 12502913
TI  - "You aren't going to get better by just sitting around": physical activity
      perceptions, motivations, and barriers in adults 75 years of age or older.
AB  - Despite accumulating evidence of cardiovascular benefits associated with physical
      activity in older people, sedentary behavior increases with age. Few physical
      activity research studies focus on underactive adults 75 years and older. In
      depth qualitative interviews using open-ended questions explored perceptions,
      motivations, and barriers to physical activity in 33 previously sedentary or
      underactive adults age > or =75. Data were analyzed using the NUD*IST (Non
      numerical, Unstructured Data Indexing, Searching, and Theorizing) qualitative
      analysis program. Participants saw sedentary behavior as harmful, considered
      themselves relatively active, were unsure of amounts of physical activity to do,
      and welcomed more physical activity information from their doctors. Motivations
      included health, independence, family, and appearances. Barriers were poor
      health, lack of time, aging, and adverse environments. Results suggest that
      people continue to be interested in physical activity as they age, but some
      misperceptions about physical activity exist. Even with health problems and age,
      physical activity counseling by doctors is valued and considered helpful by this
      age group.

PMID- 12502914
TI  - Sexual activity and the cardiac patient.
AB  - Coronary heart disease is the major cause of morbidity and mortality in the
      elderly population in the United States, affecting both men and women. Advances
      in cardiac therapies have enabled cardiac patients to remain both physically and
      sexually active even into their eighties and nineties. However, both patients and
      physicians are reluctant to discuss sexual issues. A significant number of
      patients will have sexual dysfunction following a diagnosis of cardiovascular
      disease. It is therefore imperative that physicians initiate discussions
      regarding sexual activity and potential risks to the patient such as myocardial
      infarction, sudden death, and arrhythmia. Risk stratification based on objective
      criteria and in particular cases, functional testing, may be useful in counseling
      patients regarding individual risk. Newly available pharmacologic therapies such
      as sildenafil may be useful, but must be used with caution in patients with known
      cardiovascular disease.

PMID- 12502915
TI  - Ventricular resynchronization: a promising therapy for heart failure.
AB  - Primarily a disease of the elderly, heart failure continues to be an ever
      increasing health care problem given the growth in the number of individuals over
      age 65. Although there have been many advances in the pharmacologic management of
      heart failure, there continues to be a significant number of patients with
      persistent symptoms despite maximal therapy and it is likely that this group of
      patients will only continue to increase in number. Given this, significant
      research has gone into exploring new modalities, such as device therapies, to
      treat heart failure. Of these, ventricular resynchronization has emerged as one
      of the most promising. This review will examine the most important aspects of
      ventricular resynchronization therapy including: the significance of ventricular
      dyssynchrony, the role of traditional pacemakers, the effects on contractile
      function and reverse remodeling, and the currently accepted indications for
      resynchronization devices. Additionally, various aspects of completed and ongoing
      trials will be discussed.

PMID- 12502916
TI  - Atrial fibrillation in the elderly.
AB  - Atrial fibrillation is the most common arrhythmia in the United States, whose
      incidence is greatest in the elderly population. This rhythm disorder can be
      paroxysmal or chronic and is associated with a range of clinical conditions from
      palpitations and dyspnea to stroke and death. In the elderly the mainstay of
      treatment of atrial fibrillation should utilize drug therapy. The main goals of
      drug therapy should be effective rate control to avoid tachycardia-induced
      cardiomyopathy, anticoagulation to reduce the risk of stroke and thromboembolism,
      and maintenance of sinus rhythm to prevent adverse atrial remodeling. In those
      patients in whom effective rate control cannot be achieved, catheter ablation of
      the atrioventricular node and implantation of a permanent pacemaker should be
      considered. Catheter ablation of atrial fibrillation by targeting pulmonary
      venous foci or pulmonary venous isolation currently remains investigational and
      we advocate its use be limited to symptomatic patients who have failed
      traditional therapy.

PMID- 12502917
TI  - Ethical issues in the management of geriatric cardiac patients.
AB  - A 69-year-old woman dying of severe ischemic cardiomyopathy and peripheral
      arterial disease is developing gangrene of her toes without pain or overt signs
      of infection. Should you perform an arteriogram, attempt repeat angioplasty of
      either or both limbs?

PMID- 12502918
TI  - Electrocardiology teacher analysis and review. Deceptiveness of lead II as a
      rhythm strip.

PMID- 12502919
TI  - Images in geriatric cardiology. Definitive diagnosis of aortic valve papillary
      fibroelastoma by three-dimensional transesophageal echocardiography.

PMID- 12502920
TI  - Estimating risk for percutaneous interventions in the elderly.

PMID- 12502921
TI  - Statin therapy in the elderly-the evidence mounts.

PMID- 12502922
TI  - Potential utility of uroplakin III, thrombomodulin, high molecular weight
      cytokeratin, and cytokeratin 20 in noninvasive, invasive, and metastatic
      urothelial (transitional cell) carcinomas.
AB  - The morphology of urothelial carcinomas, particularly when poorly differentiated
      or in metastatic sites, is not distinctive and overlaps significantly with other
      poorly differentiated nonurothelial carcinomas. Currently, there is no widely
      used single marker or panel of markers to confirm urothelial origin. We evaluated
      a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR),
      high molecular weight cytokeratin (HMWCK), and cytokeratin 20 (CK20) in a wide
      range of urothelial tumors. Immunohistochemistry was performed on 112 paraffin
      embedded urothelial neoplasms: 14 low malignant potential, 16 low-grade
      noninvasive, 16 high-grade noninvasive, 36 invasive, and 25 metastatic and 5
      small cell carcinomas of the urinary bladder. Tissue microarray analysis was used
      to examine 498 tissue cores of nonurothelial tumors and normal tissue using
      antibodies to UROIII, THR, and HMWCK. Overall positive staining results in all
      urothelial tumors are as follows: UROIII, 64 of 112 (57.1%); THR, 77 of 112
      (68.8%); HMWCK, 88 of 110 (80%); and CK20, 53 of 110 (48.2%). The expression of
      the four markers varied with tumor grade and stage. All small cell carcinomas
      were negative for all markers. Variant morphologic subtypes showed similar
      staining as conventional urothelial carcinomas. Tissue microarray analysis showed
      no UROIII immunoreactivity in tissue cores of nonurothelial tumors. THR was
      expressed by a limited number of nonurothelial cores (10 of 37 [27%] non-small
      cell lung carcinomas, 2 of 36 [5.6%] lymphomas). HMWCK was expressed by 43.8% of
      non-small cell lung carcinomas and essentially absent in other nonurothelial
      tumor cores. Based on the results of the study, the expression of UROIII in a
      tumor is essentially diagnostic of urothelial origin; however, it is expressed in
      only slightly more than half of urothelial tumors. The coexpression of THR,
      HMWCK, and CK20 strongly suggests urothelial origin. The coexpression of two of
      three non-UROIII markers (THR, HMWCK, CK20) suggests urothelial origin but
      requires clinicopathologic correlation. The results of the study indicate a role
      for an antibody panel that includes UROIII, THR, HMWCK, and CK20 in the diagnosis
      of urothelial tumors.

PMID- 12502923
TI  - Correlation of histologic prognostic factors in core biopsies and therapeutic
      excisions of invasive breast carcinoma.
AB  - Breast core biopsy is one of the major nonoperative methods of diagnosis.
      Increasingly, there is also a need to provide prognostic data to facilitate
      timely patient management. We present the results from 500 patients with invasive
      breast carcinoma, who underwent core biopsy followed by a therapeutic surgical
      procedure. Grade and type of the invasive and in situ carcinoma, together with
      the presence or absence of vascular invasion, were determined in both biopsy and
      definitive surgical excision and the results compared. There was 67% agreement
      with overall grade (kappa value 0.48), with scores for tubule formation,
      pleomorphism, and mitotic scoring achieving values of 82%, 73%, and 58%,
      respectively. Only 60% of grade 1 and 2 carcinomas showed concordance, but 84% of
      grade 3 tumors showed agreement between core and excision results. Tumor typing,
      vascular invasion, and grading of ductal carcinoma in situ had agreement values
      of 74%, 69%, and 65%, respectively. The major problem with assessing prognostic
      factors on needle biopsy specimens is undersampling of the most informative
      areas. However, in those patients in whom preoperative assessment of prognostic
      factors is most likely to be beneficial, i.e., those with grade 3 carcinomas, a
      high level of agreement was achieved in this large study.

PMID- 12502924
TI  - Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22
      patients.
AB  - Twenty-two Epstein-Barr virus-associated B-cell lymphoproliferative disorders
      (LPDs) without predisposing immunodeficiencies were evaluated clinically and
      pathologically. All patients were Japanese and negative for anti-human
      immunodeficiency virus antibody. They were all more than 60 years old with a
      median age of 75.5 years. Eighteen (82%) patients showed extranodal involvement.
      Biopsied specimens contained variable numbers of centroblasts, immunoblasts, and
      Reed-Sternberg-like giant cells often with necrosis and an angiocentric pattern.
      The 13 cases showing polymorphous composition and inflammatory background were
      categorized as polymorphic LPD subtype. The other nine cases contained diffuse
      proliferative lesions of large lymphoid cells and were categorized as large cell
      lymphoma subtype. Tumor cells expressed CD20 and/or CD79a, and in situ
      hybridization showed them to be associated with Epstein-Barr virus. LMP1 was
      detected in all cases and EBNA2 in seven. Eighteen patients initially received
      combination chemotherapy, and 12 achieved complete remission. However, six
      patients were refractory to chemotherapy and four patients with complete
      remission later relapsed. Eight of the 18 patients who received chemotherapy
      showed an aggressive disease course within a year after the diagnosis. There was
      a significant difference in prognosis between the group with polymorphic LPDs and
      the one with large cell lymphomas (p = 0.003). Although the disease profile of
      the 22 cases was analogous to that of immunodeficiency-associated B-cell LPDs,
      none of the patients showed evidence of underlying immunodeficiency-related
      diseases. These findings suggest that Epstein-Barr virus-associated LPD without
      immunodeficiency mainly occurs in elderly patients. Further investigations are
      needed to clarify the pathogenesis of this disease and to determine the optimal
      treatment strategy.

PMID- 12502925
TI  - Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in
      children: clinicopathologic comparative analysis of 28 cases with molecular data-
      a study from the French Federation of Cancer Centers Sarcoma Group.
AB  - The clinicopathologic and immunohistochemical features of 28 dermatofibrosarcoma
      protuberans (DFSP), giant cell fibroblastomas (GCFs), and hybrid lesions
      occurring in children are presented, including molecular data for seven of them.
      There were 19 pure adult-type DFSP (9 male and 10 female patients aged between a
      few days [neonate] and 13 years, median 7 years), 5 pure GCF (all males aged from
      2 to 8 years, median 4 years), and 4 hybrid tumors (all males aged from 1 to 4
      years, median 2.5 years). Tumor locations in pure adult-type DFSP included the
      trunk (6) and lower (11) and upper (2) limbs. Pure GCFs were observed on the
      trunk (4) and knee (1), and hybrid lesions on the trunk (2) and lower (1) and
      upper (1) extremities. Tumor size (n = 20) ranged from 0.6 to 5 cm (median 2 cm).
      Histologically, pure DFSP presented as monotonous and infiltrative, low-grade,
      dermal/hypodermal storiform spindle cell proliferations, sparing adnexal
      structures. GCF showed a dense fibrous to myxoid matrix containing slender wavy
      spindle cells and multinucleated giant stromal cells often lining angiectoid
      spaces. Hybrid lesions showed varying combinations of DFSP and GCF areas. Mitotic
      activity ranged from 1 to 3 mitoses per 10 high power fields. All tumors were
      diffusely positive for vimentin and CD34 but negative for smooth muscle actin,
      desmin, epithelial membrane antigen, and cytokeratins; one pure adult-type DFSP
      was also S-100 protein positive; <1% of nuclei were Ki67 (Mib-1) positive. One
      karyotyped adult-type DFSP showed an unbalanced t(17;22) (q22;q13) translocation.
      Multiplex RT-PCR analysis and sequencing of PCR products in seven cases showed
      gene fusion transcripts in two pure DFSP, two pure GCFs, and one hybrid lesion.
      Results were uncertain in one pure GCF; one adult-type DFSP was negative.
      Treatment procedures were known for 27 patients, consisting of 16 wide excisions
      and 11 marginal excisions. Follow-up information on 15 widely excised tumors
      (median 24 months; range 5-144 months) showed no recurrence. Five of six
      marginally excised lesions with available follow up recurred 2 months to 6 years
      (median 2 years) after initial surgery; all but one were cured by wide
      reexcision. None of the tumors metastasized. In conclusion, this study emphasizes
      1) the occurrence of adult-type DFSP in children, 2) the close relationship
      between DFSP and GCF clinically, histologically, and molecularly, 3) the
      excellent prognostic of these lesions if widely excised, and 4) the diagnostic
      usefulness of RT-PCR analyses in detecting the gene fusion transcripts resulting
      from the t(17;22) (q22;q13) in paraffin-embedded tissues.

PMID- 12502926
TI  - Paratesticular liposarcoma: a clinicopathologic study.
AB  - Paratesticular liposarcomas are rare and typically reported as isolated cases or
      as components of larger studies of liposarcomas. We studied a series of these
      tumors. All cases of paratesticular liposarcomas were retrieved from the archives
      of the Royal Marsden Hospital and the Johns Hopkins Hospital. Slides were
      reviewed and clinical information obtained. There were 30 paratesticular
      liposarcomas from men aged 41-87 years (mean 63 years; median 65 years) that
      involved the spermatic cord (23, 76%), testicular tunics (6, 20%), and epididymis
      (1, 4%). Tumors ranged from 3 to 30 cm (mean 11.7 cm; median 10 cm). Nineteen
      were well-differentiated liposarcomas (WDLs) and 10 were dedifferentiated
      liposarcomas (DDLs, five with high-grade and five with low-grade
      dedifferentiation). One was a myxoid/round cell liposarcoma with 70% round cell
      areas. All patients were treated by radical orchiectomy. One patient with WDL
      received radiation after his second recurrence and the myxoid/round cell
      liposarcoma received radiation and chemotherapy. Follow-up information was
      available for 16 of the patients, including 10 WDLs (range 24-216 months, mean
      106 months), 5 DDLs (14-30 months, median 24 months), and for the myxoid/round
      cell liposarcoma (14 months) (range for all cases 14 months to 22 years; mean 87
      months, median 36 months). Six of the WDLs (60%) recurred at 2, 4, 6, 10, 18, and
      21 years (median 8 years). The lesion that recurred at 18 years (case no. 6)
      displayed foci of high-grade dedifferentiation in the recurrence, although the
      patient was disease free at 19 years. One patient with WDL had two recurrences at
      4 and 7 years, and another had six recurrences over a 17-year period. Only one
      example of DDL recurred, at 30 months; another patient, who refused therapy for
      15 years, had a primary tumor 30 cm in diameter, displayed pulmonary metastases 1
      month after excision, and died after 14 months. The patient with MRCL had
      abdominal metastases after 1 year and was alive at 14 months. In summary,
      paratesticular WDL had a prolonged course with recurrences in more than half the
      cases, sometimes late. There were no metastases and the overall prognosis was
      good. One DDL recurred and only one of five (20%) developed metastases, but the
      mean follow-up for DDL was only 24 months.

PMID- 12502927
TI  - Epithelioid sarcoma-like hemangioendothelioma.
AB  - We are reporting seven histologically identical cases of a distinctive, low-grade
      vascular tumor that closely mimics an epithelioid sarcoma because of growth in
      solid sheets and nests, the eosinophilia of the rounded to slightly spindled
      neoplastic cells, and the diffuse, strong cytokeratin expression. Termed
      epithelioid sarcoma-like hemangioendothelioma, all were diagnosed by the
      submitting pathologist or another expert consultant as epithelioid sarcoma.
      Although none displayed architectural evidence of vascular differentiation in the
      form of multicellular vascular channels, some displayed subtle cytologic features
      of vascular differentiation and all displayed immunohistochemical evidence of
      endothelial differentiation. The patients (four male; three female) ranged in age
      from 17 to 54 years (median 23 years). Ranging in size from 1 to 3.5 cm, they
      occurred in the extremities (n = 5), scalp (n = 1), and chest wall (n = 1), both
      in deep (n = 3) and superficial (n = 3) soft tissue or both (n = 1). The tumors
      were characterized by sheets, ill-defined nodules, or fascicles of deeply
      eosinophilic cells set within a desmoplastic stroma. Multicellular vascular
      channel formation and/or hemorrhage were absent in all cases. In four cases
      intracytoplasmic vacuolization suggestive of intracytoplasmic vascular lumen
      formation was noted. The typical neoplastic cell was large and rounded in shape
      but modulated in areas to a spindled or multipolar shape. Mitotic activity was
      low (<5 mitotic figures/50 high power fields), nuclear pleomorphism was mild to
      moderate, and necrosis was absent. The tumors were positive for cytokeratin (6 of
      6), vimentin (6 of 6), CD31 (5 of 6), FLI-1 (6 of 6), but negative for CD34 (0 of
      6). Within a follow-up period of 3-72 months (median 39 months), two patients
      experienced a local recurrence and one patient regional soft tissue metastases,
      but no distant ones. Two patients presented with multifocal lesions suggestive of
      regional metastases. Currently, two patients are alive with disease and five are
      disease free. Epithelioid sarcoma-like hemangioendothelioma appears to be a
      largely unrecognized epithelioid vascular tumor with an indolent course. Despite
      its similar clinical and histologic features, it differs from epithelioid sarcoma
      by the presence of endothelial markers and the absence to date of distant
      metastases. Its distinction from other epithelioid vascular lesions is discussed.
      We think this tumor fits best into the family of "hemangioendothelioma" or
      vascular lesions of intermediate malignancy.

PMID- 12502928
TI  - Expression of FKBP12 in benign and malignant vascular endothelium: an
      immunohistochemical study on conventional sections and tissue microarrays.
AB  - FKBP12 is a cytosolic FK506 binding protein that interacts with calcineurin and
      thereby mediates the immunosuppressive effects of FK506. Because initial
      immunohistochemical staining showed abundant expression of FKBP12 in vascular
      endothelial cells, we evaluated whether it could serve as a marker for vascular
      neoplasms. We performed immunohistochemical staining of conventional sections
      from formalin-fixed, paraffin-embedded tissue from 59 benign and malignant
      vascular neoplasms using a polyclonal rabbit antiserum against FKBP12. Western
      blot analysis of tissue from 6 angiosarcomas showed a single band at 12 kD,
      consistent with the published molecular weight for the FKBP12 protein. Together,
      CD31, CD34, and FKBP12 identified all 59 vascular neoplasms in this study.
      Specificity of immunohistochemical staining was assessed on 1,321 tissues
      represented on 7 tissue microarrays. All proteins were occasionally expressed in
      non-vascular tissue. Six of 8 vascular neoplasms represented on the arrays
      stained for FKBP12, as did normal vessels in numerous cores. The polyclonal
      antiserum shows comparable sensitivity (94.9%) and specificity (96.5%) to CD34
      and CD31 and may be a useful additional marker for vascular differentiation.
      Because we have evaluated a large number of tissues by tissue microarray, we
      anticipate that our estimate of the specificity of immunostaining for FKBP12 as a
      marker for vascular endothelium will be accurate. In addition, our findings may
      explain the toxic effects of FK506 on vascular endothelium of the kidney.

PMID- 12502929
TI  - Morphologic reappraisal of serrated colorectal polyps.
AB  - The "hyperplastic polyp" is considered a benign lesion with no malignant
      potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The
      morphologic complexity of the serrated adenoma varies from being clearly
      adenomatous to being difficult to distinguish from hyperplastic polyp, which
      creates a need for more detailed morphologic analysis of all serrated polyps. We
      evaluated 24 morphologic variables in 289 serrated polyps from the colon and
      rectum. Cluster analysis and discriminant analysis were performed. A subset of
      polyps was immunostained for hMLH1 and hMSH2. Major differences were found
      between right-sided and left-sided polyps. A distinct group of serrated polyps
      with abnormal proliferation was identified throughout the colon and rectum. These
      polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps
      with normal proliferation. Left-sided serrated polyps with normal proliferation
      further clustered into three groups: vesicular cell-type, goblet cell-type, and
      mucin-poor-type. We recommend evaluation of the localization, size, and
      morphologic features when serrated polyps are included in colorectal
      carcinogenesis research. Polyps with abnormal proliferation are similar to the
      polyps in "hyperplastic polyposis" and, because of their decreased expression of
      hMLH1 and hMSH2, may be the subset of polyps associated with the development of
      colorectal carcinoma via the microsatellite instability pathway.

PMID- 12502930
TI  - Immunohistochemical distinction of invasive from noninvasive breast lesions: a
      comparative study of p63 versus calponin and smooth muscle myosin heavy chain.
AB  - Identification of myoepithelial cells using antibodies to cytoskeletal proteins,
      such as smooth muscle myosin heavy chain (SMM-HC) and calponin, can play an
      important role in distinguishing invasive carcinoma from its histologic mimics.
      However, antibodies to these proteins may also cross-react with stromal
      myofibroblasts and vascular smooth muscle cells. It has recently been
      demonstrated that myoepithelial cells express the nuclear protein, p63, a member
      of the p53 gene family. We compared the patterns of reactivity of antibodies with
      p63, calponin, and SMM-HC on 85 breast lesions, including 11 cases of sclerosing
      adenosis, 33 cases of ductal carcinoma in situ, including 10 that showed
      microinvasion, 6 cases of lobular carcinoma in situ, and 35 cases of infiltrating
      ductal carcinoma. All three antibodies were positive on the vast majority of
      myoepithelial cells in all cases. A small minority of cases showed focal gaps in
      the revealed myoepithelial cell layer, reflected in discontinuous positive
      immunostaining around noninvasive epithelial nests (including ductal carcinoma in
      situ). No case showed p63 expression by myofibroblasts or vascular smooth muscle
      cells, whereas myofibroblasts expressed, in 8% and 76% of cases, SMM-HC and
      calponin, respectively. Although no tumor cell reactivity was noted with
      antibodies to calponin or SMM-HC, tumor cells in 11% of cases showed at least
      focal p63 expression. And although antibodies to p63 offer excellent sensitivity
      and increased specificity for myoepithelial detection relative to antibodies to
      calponin and SMM-HC, they have the following diagnostic limitations: 1) they
      occasionally demonstrate an apparently discontinuous myoepithelial layer,
      particularly around ductal carcinoma in situ, and 2) they react with a small but
      significant subset of breast carcinoma tumor cells. p63 may represent a
      myoepithelial marker that can complement or replace SMM-HC and/or calponin in the
      analysis of difficult breast lesions.

PMID- 12502931
TI  - Dissolution of the lymphoid follicle is a feature of the HHV8+ variant of plasma
      cell Castleman's disease.
AB  - The plasma cell variant of Castleman's disease (PCD) may occur in a variety of
      clinical settings. One recently delineated type of PCD is caused by human
      herpesvirus 8 (HHV8) infection. Lymph nodes from 25 patients with PCD, including
      six HHV8+ and 19 HHV8- cases, were studied. Three patients with HHV8+ PCD were
      also infected with human immunodeficiency virus-1. Features common to all cases
      were interfollicular plasmacytosis and variably hyperplastic and regressed
      follicle germinal centers. Features associated only with HHV8+ PCD included
      follicle dissolution resulting from blurring of the mantle zone boundary (p =
      0.0001), presence of atypical plasma cells and immunoblasts within these areas (p
      = 0.0006), and more prominent interfollicular vascular proliferation than in HHV8
      PCD. HHV8+ cells were predominantly immunoblasts and small lymphocytes that were
      highly enriched in the mantle zones of altered follicles. These areas showed a
      predominance of plasmacytoid forms expressing lambda light chain in four of six
      cases. The extrafollicular fibroblastic network surrounding altered germinal
      centers demonstrated marked upregulation of low-affinity nerve growth factor
      receptor in five of five HHV8+ cases but in only two of 10 HHV8- cases. We
      conclude that HHV8+ PCD is distinctive histologically because of the accumulation
      of infected lymphocytes in the mantle zone leading to progressive dissolution of
      the germinal center and altered regulation of the surrounding stroma.

PMID- 12502932
TI  - Early-stage lung adenocarcinomas with a micropapillary pattern, a distinct
      pathologic marker for a significantly poor prognosis.
AB  - Adenocarcinomas with a micropapillary pattern (MPP), featuring small papillary
      tufts lacking a central fibrovascular core, are thought to have a poor prognosis.
      To examine whether the MPP is a predictor of prognosis, clinicopathologic
      characteristics of adenocarcinomas were analyzed with particular reference to
      survival of early-stage patients. The subjects were 344 consecutive patients
      (female/male ratio 163:181) for whom complete surgical resection was undertaken
      at the Cancer Institute Hospital, Japan, during 1986-1995. Histologically, they
      were divided into two groups: MPP-positive (n = 139; 40%) and MPP-negative (n =
      205; 60%). The following items were significantly more frequent in the MPP
      positive group: metastasis to lymph nodes (p <0.001), pleural invasion (p =
      0.02), intrapulmonary metastasis (p <0.001), and nonsmoking status (p = 0.002).
      In stage I patients (i.e., without lymph node metastasis, n = 154), 5-year
      survival of the MPP-positive group (n = 45) was 79%, significantly lower than the
      MPP-negative group (n = 109) of 93% (p = 0.004). In many cases of the c-stage I
      MPP-positive group, upstaging was necessary on the basis of pathologic findings
      for metastases, and the survival was between stage I and stage II. Our study
      clearly indicated that the MPP is a distinct prognostic marker for lung
      adenocarcinoma, particularly regarding apparent stage I diseases.

PMID- 12502933
TI  - Pancreaticoduodenectomy (Whipple resections) in patients without malignancy: are
      they all 'chronic pancreatitis'?
AB  - Pancreaticoduodenectomy (Whipple resection) has evolved into a safe procedure in
      major high-volume medical centers for the treatment of pancreatic adenocarcinoma
      and refractory chronic pancreatitis. However, some Whipple resections performed
      for a clinical suspicion of malignancy reveal only benign disease on pathologic
      examination. We evaluated the frequency of such Whipple resections without tumor
      in a large series of pancreaticoduodenectomies and classified the diverse
      pancreatic and biliary tract diseases present in these specimens. Of 442 Whipple
      resections performed during 1999-2001, 47 (10.6%) were negative for neoplastic
      disease and, in 40 cases, had been performed for a clinical suspicion of
      malignancy. Most Whipple resections revealed benign pancreatic disease, including
      8 (17%) alcohol-associated chronic pancreatitis, 4 (8.5%) gallstone-associated
      pancreatitis, 1 (2.1%) pancreas divisum, 6 (12.8%) "ordinary" chronic
      pancreatitis of unknown etiology, and 11 (23.4%) lymphoplasmacytic sclerosing
      pancreatitis. In particular, patients with lymphoplasmacytic sclerosing
      pancreatitis were all thought to harbor malignancy, whereas only 13 of 19 (68.4%)
      of Whipple resections showing histologically "ordinary" forms of chronic
      pancreatitis were performed for a clinical suspicion of malignancy. Benign
      biliary tract disease, including three cases of primary sclerosing cholangitis,
      two cases of choledocholithiasis-associated chronic biliary tract disease, and
      four fibroinflammatory strictures isolated to the intrapancreatic common bile
      duct, was a common etiology for clinically suspicious Whipple resections (22.5%
      of cases). Pancreatic intraepithelial neoplasia (PanIN) was a common finding
      among all pancreata, whether involved by pancreatitis or histologically normal.
      Overall, PanIN 1A/1B was present in 68.1%, PanIN 2 in 40.4%, and PanIN 3 in just
      2.1%. These findings indicate that "benign but clinically suspicious" Whipple
      resections are relatively common in high-volume centers (9.2%) and reveal a
      diverse group of clinicopathologically distinctive pancreatic and biliary tract
      disease.

PMID- 12502934
TI  - Pharmacopathology: a new spin on an old idea.

PMID- 12502935
TI  - Adenocarcinoma of the thymus: report of two cases, including a previously
      undescribed mucinous subtype.
AB  - We report two cases of primary thymic adenocarcinoma, a very uncommon neoplasm
      with limited information in the literature. Both patients were men (age 15 and 39
      years). The first case was a mucinous carcinoma, a subtype of adenocarcinoma not
      previously recognized in the thymus. It comprised islands and strips of mucin
      rich tumor cells floating in large pools of extracellular mucin. There was
      transition of carcinomatous epithelium to the attenuated epithelium of a thymic
      cyst. Immunostaining for high molecular weight cytokeratin furthermore
      highlighted in one area negatively stained tumor islands wrapped by positively
      stained residual thymic medullary epithelium, suggesting in situ origin of the
      carcinoma from the thymic epithelium. The second case was a papillary carcinoma
      with high nuclear grade and many psammoma bodies. It showed strong
      immunoreactivity for CD5 and did not stain for CA-125 as well as thyroid,
      pulmonary, and mesothelial markers. The findings in this study therefore broaden
      the morphologic spectrum of thymic adenocarcinomas to include a mucinous subtype.
      Review of the literature indicates that thymic adenocarcinomas usually arise from
      thymic cyst or type A thymoma, and the clinical outcome is variable.

PMID- 12502936
TI  - Clear cell meningioma of the fourth ventricle.
AB  - Clear cell meningioma (CCM) has been identified and included in the World Health
      Organization classification of CNS tumors recently. CCMs are histologically
      characterized by sheets of polygonal cells with clear cytoplasm, which is the
      expression of high glycogen concentration. Compared with other variants of
      meningiomas, CCMs occur in younger patients and usually are located in the spinal
      canal and posterior fossa, the last ones mainly in the cerebellopontine angle.
      Some reports suggest that CCMs have high recurrence rate and potentially
      aggressive behavior. Poor outcome has been shown in intracranial and spinal tumor
      location, but indicators that predict outcome have not been established. The
      authors present two cases of intracranial CCMs, with excellent outcome in
      patients harboring tumor location (restricted to the fourth ventricle) and some
      clinical particular features (young age, gender, obesity, and moderate impairment
      of intellectual capacity). To the best of our knowledge, these are the two first
      reported cases of clear cell meningioma located primarily in the fourth
      ventricle.

PMID- 12502937
TI  - Sporadic versus familial medullary thyroid microcarcinoma.

PMID- 12502938
TI  - Prevalence of HIV with conjunctival squamous cell neoplasia in an African
      provincial hospital.
AB  - PURPOSE: To evaluate the prevalence of HIV seropositivity among patients with
      malignant conjunctival squamous cell carcinoma (SCC) and carcinoma in situ (CIS)
      and to reassess the potential linkage, albeit well documented, between ocular
      surface epithelial dysplasia (OSED) and HIV infection. PATIENTS AND METHODS: A
      case-control design study was conducted in an African provincial hospital. Twenty
      three African black patients underwent excisional biopsy of conjunctival
      malignant lesions. In 18 of these patients, ELISA for HIV antibodies was
      performed prior to the excisional biopsy. RESULTS: Pathological evaluation
      revealed SCC in 12 (52%) patients, CIS in six (26%) patients, and Kaposi sarcoma
      (KS) in five (22%) patients. Eighteen patients (78.3%) agreed to take a
      serological HIV test, and among these, seropositivity for HIV was significantly
      (p < 0.01) higher (92.3%, 12 of 13) in the SCC/CIS subgroup than in a control
      group with benign conjunctival lesions (28.5%, two of seven). The most common
      (91.7%) clinical finding in the SCC/CIS/HIV group (12 patients) was corneal
      overriding. Conjunctival malignancy was the first presenting sign for AIDS in 50%
      of our patients. CONCLUSIONS: A significantly high rate of HIV seropositivity was
      found in a group of African black patients with conjunctival SCC/CIS compared
      with a control group with benign conjunctival lesions. The direct correlation
      between HIV infection and SCC/CIS was reconfirmed in a case-control study.
      Therefore, an HIV test should probably be performed in cases of conjunctival
      SCC/CIS or dysplasia, especially among patients in high-risk populations.

PMID- 12502939
TI  - Study of corneal topographic patterns with single continuous suturing techniques
      in penetrating keratoplasty.
AB  - PURPOSE: To study the corneal topographic patterns following three different
      types of single continuous suturing techniques in penetrating keratoplasty.
      METHODS: One hundred forty-eight maps obtained from 40 patients who underwent
      penetrating keratoplasty with single continuous suturing were retrospectively
      analyzed at a tertiary eye care center. The videokeratograph maps were obtained
      on the Eye Sys System 2000 at 1, 3, and 6 months after surgery. Suture adjustment
      was done for cases with astigmatism greater than 3 diopters, and maps were also
      obtained after suture adjustment. The maps were classified according to the
      corneal profile and the astigmatic pattern seen in the topographic maps. RESULTS:
      Combined prolate patterns were seen most frequently, and their proportion was
      significantly higher at 1 month ( p= 0.009), 3 months ( p= 0.0004), and 6 months
      ( p= 0.0008). The simulated keratometric astigmatism was significantly higher in
      the prolate group compared with the other groups at 1 month ( p= 0.0021).
      However, all the topographic patterns showed comparable magnitude of astigmatism
      after suture adjustment and at 3 and 6 months. The antitorque suturing technique
      showed a higher proportion of prolate maps compared with the other suturing
      techniques. CONCLUSIONS: Prolate patterns of the cornea are the most frequently
      seen patterns after single continuous suturing, which is the normal physiological
      pattern of the cornea. The initial astigmatism is higher in the prolate pattern,
      which can be successfully reduced with suture adjustment.

PMID- 12502940
TI  - Effects of lacrimal occlusion with collagen and silicone plugs on patients with
      conjunctivitis associated with dry eye.
AB  - PURPOSE: To determine whether canalicular occlusion with collagen and silicone
      plugs reduces the severity of symptoms in patients with conjunctivitis secondary
      to dry eye. METHODS: This was a prospective, randomized, double-masked study
      conducted at a single center in Mexico, in which 61 patients with dry
      eye/conjunctivitis were assigned to progressive lacrimal occlusion with collagen
      and silicone plugs or a sham procedural group. Outcome variables included total
      and individual dry eye and conjunctivitis symptom scores, moisturizing agent
      usage, best-corrected visual acuity, ocular comfort level, visual performance,
      corneal/conjunctival fluorescein staining, and incidence of adverse events.
      RESULTS: Total dry eye and conjunctival symptom scores were reduced by 43.7 and
      33.7%, respectively 2 weeks after occlusion of all four lacrimal canaliculi with
      collagen plugs, increasing to 77.4 and 72.1% 2 weeks later following superior
      canalicular occlusion of both eyes with silicone plugs and inferior placement of
      collagen plugs. At the 8-week visit (4 weeks after silicone plug implantation of
      the inferior canaliculi of both eyes), the reduction in total dry eye and
      conjunctival symptom scores further increased to 94.2 and 93.0%, respectively,
      accompanied by a marked decline in each of the seven individual symptom scores
      (dryness, watery eyes, itching, burning, foreign body, fluctuating vision, and
      light sensitivity). In concert with these changes, moisturizing agent usage and
      corneal/conjunctival fluorescein staining decreased in a progressive fashion over
      the 8-week study period, and best-corrected visual acuity, ocular comfort, and
      visual performance improved in the absence of any treatment-related adverse
      events except for one case of epiphora. The response of patients to lacrimal
      occlusion can be sharply contrasted with the sham procedure group, which remained
      relatively unchanged from baseline at each of the study visits. CONCLUSIONS:
      Progressive lacrimal occlusion with collagen and silicone plugs was of clinical
      benefit to patients with dry eye and conjunctivitis.

PMID- 12502941
TI  - Correlation of corneal sensation, but not of basal or reflex tear secretion, with
      the stage of diabetic retinopathy.
AB  - PURPOSE: To examine the possible relation between corneal sensation or tear
      secretion and the stage of diabetic retinopathy in diabetic patients. METHODS:
      Total reflex or basal tear secretion and corneal sensation were determined in 95
      patients with type II diabetes mellitus and 58 nondiabetic control subjects. Tear
      secretion was measured by the Schirmer test and corneal sensation with a Cochet
      Bonnet esthesiometer. RESULTS: Corneal sensation and total or reflex tear
      secretion were significantly reduced in diabetic patients compared with
      nondiabetic controls. The loss of corneal sensation, but not that of tear
      secretion, was significantly correlated with stage of diabetic retinopathy in
      diabetic patients who were diagnosed with no diabetic retinopathy, simple
      diabetic retinopathy, preproliferative retinopathy, or proliferative retinopathy.
      CONCLUSION: Both corneal sensation and total or reflex tear secretion are reduced
      in individuals with diabetes. The decrease in corneal sensation, but not that in
      each tear secretion, was correlated with the stage of diabetic retinopathy. Given
      that loss of corneal sensation is a manifestation of diabetic polyneuropathy,
      these results are consistent with the notion that both diabetic retinopathy and
      polyneuropathy result from a basement membrane abnormality.

PMID- 12502942
TI  - Recurrence of corneal stromal dystrophies after penetrating keratoplasty.
AB  - PURPOSE: To assess the rates of simple and clinically significant recurrences of
      stromal dystrophies in corneal grafts. METHODS: We conducted a retrospective
      review of Wills Eye Hospital records from 1984 to 2001, identifying all patients
      with stromal corneal dystrophies who had penetrating keratoplasties. Kaplan-Meier
      curves and chi analysis were performed. RESULTS: The study population consisted
      of 35 eyes (21 patients) with lattice dystrophy, 17 eyes (10 patients) with
      corneal dystrophy of Bowman's membrane (CDB), 14 eyes (eight patients) with
      macular dystrophy, seven eyes (five patients) with granular dystrophy, and four
      eyes (four patients) diagnosed with Schnyder's crystalline dystrophy. There was a
      simple recurrence in 21 (60%) eyes (14 patients) with lattice and in 15 (88%)
      eyes (eight patients) with CDB. The median time to simple recurrence for the
      first eye transplanted of each patient was 8.4 years for lattice and 2.0 years
      for CDB. After 5 years of follow-up, there was a clinically significant
      recurrence, manifested by recurrent erosions or associated with decreased visual
      acuity, in the first eye transplanted of each patient, respectively, in six
      (17.1%) and seven (20%) eyes with lattice and in two (11.8%) and three (17.6%)
      eyes with CDB. CONCLUSION: Corneal dystrophy of Bowman's membrane has the highest
      rate of simple recurrence followed by granular and lattice dystrophies,
      respectively. However, the rate of clinically significant recurrence, both
      recurrent erosions and decreased visual acuity, in the first 5 years is similar
      in CDB and lattice dystrophies. Recurrence is infrequent in macular and
      Schnyder's crystalline dystrophy. As expected, in genetic diseases, the potential
      for recurrence exists and increases with follow-up time.

PMID- 12502943
TI  - Keratoconus-like topographic changes in keratoconjunctivitis sicca.
AB  - PURPOSE: To describe a case of inferior corneal steepening with a keratoconus
      like pattern in a patient with nocturnal lagophthalmos and aqueous tear
      deficiency (ATD). METHODS: Axial curvature mapping was performed with the Tomey
      TMS-2N videokeratoscopy instrument. Keratoconus-like topography patterns were
      identified with the Klyce Software package of this instrument. RESULTS: Axial
      videokeratoscopy showed asymmetric inferior corneal steepening in the right eye.
      The surface regularity index (SRI), surface asymmetry index (SAI), and the
      simulated keratometric cylinder change (CYL) were 1.05, 5.05, and 0.75,
      respectively. The keratoconus screening indices were as follows for the right
      eye: Klyce/Maeda index of 95% similarity (clinical keratoconus interpreted) and
      Smolek/Klyce index of 23.09% severity (keratoconus suspect interpreted).
      Ultrasound pachymetric mapping showed a normal central corneal thickness. We
      found a similar topographic pattern of keratoconus in seven eyes of 74 dry eye
      patients who were previously evaluated with the Tomey TMS-2N. CONCLUSION: Chronic
      ocular desiccation and aqueous tear deficiency can produce inferior corneal
      steepening and high astigmatism resembling keratoconus.

PMID- 12502944
TI  - Lacrimal histopathology and ocular surface disease in a rabbit model of
      autoimmune dacryoadenitis.
AB  - PURPOSE: To study the effects of induced autoimmune dacryoadenitis on lacrimal
      gland function, histopathology, and ocular surface disease in a rabbit model.
      METHODS: One lacrimal gland was surgically excised from each experimental rabbit,
      and epithelial cells were purified, cultured, irradiated, and then cocultured
      with autologous peripheral blood lymphocytes (PBLs) for 5 days. Autoimmune
      dacryoadenitis was induced by injecting the autologous mixed cell reactions
      (AMCRs) into the rabbit's remaining lacrimal gland. Normal rabbits and rabbits
      with both lacrimal glands injected with nonstimulated PBLs were examined as
      controls. Eyes were evaluated biweekly for 8 weeks by slit-lamp biomicroscopy,
      Schirmer testing, tear break-up time measurement, and rose bengal examination.
      Sections of lacrimal glands removed at 8 weeks post-operation were immunostained
      using antibodies against rabbit class II major histocompatibility complex
      molecule (MHC-II), CD4, CD8, CD18, and rabbit thymic lymphocyte antigen (RTLA).
      Relative numbers of positively stained cells were quantified with a ChromaVision
      image analysis system. RESULTS: During an 8-week period, a continuous decrease in
      tear production and stability, accompanied by a continuous increase in rose
      bengal staining, occurred in eyes in which AMCR-PBL had been injected into the
      ipsilateral lacrimal glands. Similar, though generally less severe, changes
      occurred in eyes contralateral to the AMCR-PBL-injected eyes. No obvious changes
      by 8 weeks in these parameters were found in eyes in which the lacrimal glands
      had been injected with nonstimulated PBLs or in the lacrimal gland-excised eyes
      contralateral to normal eyes. Interstitial cells in normal lacrimal glands
      expressed CD18 and RTLA antigens, but few expressed CD4, CD8, or MHC-II. Focal
      mononuclear cell infiltrates were only found in lacrimal glands from animals with
      induced autoimmune dacryoadenitis. These cells were predominantly positive for
      CD4 (7.3-fold increase), RTLA (7.8-fold increase), or CD18 (42-fold increase).
      MHC-II expression in interstitial and ductal epithelial cells was also
      significantly greater in these animals than in control animals. The mononuclear
      cell infiltrates were frequently found enveloping venules, some of which appeared
      to be high endothelial cell venules. The ductal epithelium also contained CD4 and
      CD8 immunopositivity, within the epithelium, at the lumenal surface, or
      surrounding the ducts. Occasionally CD4 and CD8 immunopositive cells could be
      identified within the acinar lumens. CONCLUSIONS: Injection of activated PBLs
      (i.e., AMCR-PBLs) in the lacrimal gland induces autoimmune dacryoadenitis with
      immunopathologic features similar to those of Sjogren's syndrome. The lacrimal
      immunopathology is accompanied by typical clinical manifestations of dry eye
      syndrome. The persistent significant dry eye does not appear to result just from
      failure of the diseased gland but from a more general dysfunction of the surface
      secretory tissues.

PMID- 12502945
TI  - Activity of voriconazole against corneal isolates of Scedosporium apiospermum.
AB  - PURPOSE: To determine the in vitro antifungal activity of voriconazole, a new
      triazole, compared with other polyene and imidazole antifungal agents against
      corneal isolates of Scedosporium apiospermum. METHODS: Macro-broth dilution
      susceptibility testing was performed on five isolates of S. apiospermum obtained
      from patients with keratomycosis to determine the minimal inhibitory
      concentrations (MICs) for amphotericin B, natamycin, ketoconazole, itraconazole,
      and voriconazole. The use of oral voriconazole in the management of a patient
      with posttraumatic S. apiospermum keratitis is described. RESULTS: S. apiospermum
      is generally resistant to commonly used topical ophthalmic antifungal agents. The
      MIC of voriconazole was 0.5 microg/mL, a concentration lower than that of other
      imidazoles. CONCLUSION: Voriconazole has promising activity against and may prove
      useful in the management of fungal keratitis.

PMID- 12502946
TI  - Staining characteristics of preserved human amniotic membrane.
AB  - PURPOSE: Amniotic membrane is an ultra-thin cellophane-like membrane that is used
      in ocular surface reconstruction. We evaluated the staining characteristics of
      commonly available dyes on preserved human amniotic membrane to aid in handling
      of amniotic membrane during transplantation. METHODS: Five dyes, indocyanine
      green (2.5%, 1.0%, and 0.5%), fluorescein (0.25%), rose bengal (1%), lissamine
      green B (1%), and trypan blue (0.5%), were used to stain amniotic membrane. After
      staining, the specimens were observed under a dissecting microscope to evaluate
      for the uptake of the stains. Positively stained membranes were evaluated for the
      persistence of staining by placing them in 2 to 3 mL of balanced saline solution
      that was changed every 30 minutes over 6 hours. RESULTS: Preserved human amniotic
      membrane is stained by indocyanine green, rose bengal, lissamine green B, and
      trypan blue. Of these four dyes, only the membrane stained with 1% lissamine
      green B was free of stain after 120 minutes. Indocyanine green, rose bengal, and
      trypan blue continued to strongly stain the membrane after 24 hours. CONCLUSIONS:
      Indocyanine green, rose bengal, trypan blue, and lissamine green B all stain
      amniotic membrane. Lissamine green B appears to have advantages over the other
      dyes in that it will stain the membrane well, and in our model, dissipate in 120
      minutes. Intraoperative staining with lissamine green B may be a simple and
      effective way to assist surgeons in the proper handling of amniotic membrane.

PMID- 12502947
TI  - MUC7 expression in the human lacrimal gland and conjunctiva.
AB  - PURPOSE: Several mucins including MUC1, MUC2, MUC4, and MUC5AC have been
      identified at the ocular surface and in tears. The lacrimal gland, however, is
      not generally considered a source of ocular mucin. Because the lacrimal glands
      are similar to the salivary glands, we hypothesized that the lacrimal gland would
      express MUC7, a distinctive salivary mucin. We report the presence of MUC7 RNA
      and protein in normal human lacrimal glands as determined by reverse
      transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and
      Western blot analysis. METHODS: RNA from lacrimal glands and conjunctivae was
      isolated and subjected to RT-PCR with primers specific for MUC7. The identity of
      the PCR products was confirmed by sequencing. In situ hybridization with PCR
      product-based riboprobes was used to locate MUC7 transcripts in the lacrimal
      gland. MUC7 protein was detected by Western blot analysis. RESULTS: Of six normal
      human lacrimal glands from which relatively intact mRNA could be extracted, four
      expressed MUC7. Hybridization with an antisense riboprobe for MUC7 indicates the
      presence of MUC7 transcripts in the cytoplasm of acinar cells. Western blot
      analysis confirms expression of the protein in the lacrimal gland. The presence
      of MUC1, MUC4, and MUC5B was also demonstrated by RT-PCR in lacrimal gland
      tissue. MUC7 transcripts and protein were also detected in normal human
      conjunctivae. CONCLUSIONS: The mucin profile of the lacrimal gland resembles that
      of the salivary gland. Both RNA and protein corresponding to MUC7 are present in
      the normal human lacrimal gland. Reverse transcription-polymerase chain reaction
      indicates that other transcripts of MUC1, MUC4, and MUC5B are present as well.
      Ocular MUC7 is also produced by the conjunctival mucosa. The lacrimal gland,
      therefore, contributes not only to the aqueous component of tears but also, in
      concert with the conjunctiva, may contribute to the total pool of ocular surface
      mucins.

PMID- 12502948
TI  - Optical coherence tomography for the detection of laser in situ keratomileusis in
      donor corneas.
AB  - PURPOSE: In 2001, more than one million laser in situ keratomileusis (LASIK)
      procedures were performed worldwide. Considering the increasing number of
      refractive procedures, eye banks will be increasingly confronted with the problem
      of how to identify those donors with prior refractive surgery. To date, efficient
      screening methods to identify LASIK surgery in donor eyes have not been
      established. Therefore, the purpose of the current study was to determine whether
      optical coherence tomography (OCT) can be used to detect the presence of LASIK
      induced changes in human corneas. METHODS: Laser in situ keratomileusis was
      performed on 20 organ-cultured human cornea disks. The excimer laser ablation
      performed ranged from 0 to 12 diopters. The corneas were maintained in culture,
      and the visibility of flap-stromal interface by OCT was assessed up to 6 months
      after the LASIK procedure. Additionally, two donor corneas with the history of
      LASIK treatment before death were screened for structural changes. RESULTS:
      Optical coherence tomography scans were able to detect the interface between the
      corneal flap and the residual stromal tissue in all corneas and at all examined
      time intervals. There were no differences in signal intensity among the different
      depths of ablation. The relative signal intensity of the interface compared with
      the averaged stromal intensity ranged from 2.1 to 6.0. In both donor corneas with
      suspected prior LASIK surgery, OCT scanning showed the characteristic stromal
      interface as found in the in vitro model. CONCLUSIONS: Corneal examination by OCT
      could be an appropriate technique for eye banks to screen donor corneas for prior
      LASIK surgery.

PMID- 12502949
TI  - Candida parapsilosis keratitis.
AB  - PURPOSE: To present clinical, microbiologic, and histopathologic features of
      keratitis due to Candida parapsilosis. METHODS: Clinicomicrobiologic evaluation
      of four patients (four eyes) with culture-proven C. parapsilosis keratitis. The
      patients were evaluated for symptoms, visual acuity, clinical observations,
      microbiologic examination of corneal scrapings, and pathologic examination of
      corneal buttons. RESULTS: Three cases were observed after penetrating
      keratoplasty, and one case occurred after inhalation of corticosteroids. Clinical
      presentation of C. parapsilosis keratitis showed a great diversity. There was one
      case of crystalline keratopathy and three cases of suppurative corneal
      infiltrate. Histopathology of corneal buttons showed interlamellar accumulations
      of yeast. Medical treatment included topical amphotericin B and systemic
      triazoles. Penetrating keratoplasty was required in three patients. CONCLUSION:
      Risk factors for C. parapsilosis keratitis may include corticosteroid use and
      prior corneal transplantation. The prognosis of C. parapsilosis keratitis with
      antifungal and surgical therapy may vary from good visual outcome to intraocular
      extension with phthisis bulbi.

PMID- 12502950
TI  - In vivo confocal microscopy of corneal insect foreign body.
AB  - PURPOSE: To report a case of insect corneal foreign body with in vivo confocal
      microscopy performed. METHODS: Clinical presentation, clinical pictures, and
      treatment are discussed. Confocal microscopy of the injured cornea was performed
      in areas showing foreign bodies with and without infiltrations seen under the
      slit-lamp. CONCLUSION: Confocal microscopy is useful in detection of subtle
      inflammatory reaction, monitoring the progress of the injury and decision of
      treatment plans.

PMID- 12502951
TI  - A corneal diffuse neurofibroma as a manifestation of von recklinghausen disease.
AB  - PURPOSE: To report a case of a primary corneal diffuse neurofibroma in a patient
      with von Recklinghausen disease (NF-1). METHODS: Case report. A physical
      examination and histopathology were performed. The immunohistochemical studies
      were performed using an avidin-biotin-peroxidase complex technique on formalin
      fixed and paraffin-embedded tissue. Histologic sections from corneal tissue were
      incubated with primary antibodies against vimentin and S-100 protein. A
      complementary ultrastructural study of the same formalin-fixed and paraffin
      embedded tissue was made. RESULTS: The ophthalmologic examination revealed a
      yellowish-white elevated mass that involved the supratemporal cornea but not the
      limbus. Histologic study showed a tumor of the peripheral nerve sheath, a diffuse
      neurofibroma in the corneal stroma, and proliferation of spindle cells with
      markedly elongated nuclei. Cells comprising the tumor reacted with vimentin and S
      100 protein, and the ultrastructural studies revealed myelinated nerve fibers
      confirming the diagnosis. CONCLUSION: The development of a primary diffuse
      neurofibroma in the cornea of patients with von Recklinghausen disease is
      possible. The present case supports the statement that neurofibromas arising from
      the peripheral nerve sheath may involve any part of the body.

PMID- 12502952
TI  - Surgical treatment of chronically recurring pterygium.
AB  - PURPOSE: To report the result of a combined surgical procedure of pterygium
      excision with simultaneous amniotic membrane transplant, conjunctival limbal
      autograft, and mitomycin C application in the management of two cases of
      chronically recurring pterygium. METHODS: Report of two cases. RESULTS: The two
      male patients, ages 24 and 42 years, had undergone six previous surgeries for
      pterygium, with and without adjunct procedures. In the follow-up period of 26
      months for the first case and 25 months for the second case, no recurrence or
      complications were encountered. CONCLUSION: A combined procedure seems to be
      beneficial in cases of chronically recurring pterygia in younger patients. This
      approach may be considered when all other types of surgery have failed.

PMID- 12502953
TI  - Late traumatic displacement of laser in situ keratomileusis flaps.
AB  - PURPOSE: To report the occurrence, management, and outcome of late-onset
      traumatic dehiscence and dislocation of laser in situ keratomileusis (LASIK)
      flaps. METHODS: Two interventional case reports of patients with late-onset LASIK
      corneal flap dislocation after ocular trauma occurring at 7 and 26 months after
      surgery, respectively. RESULTS: The flaps were lifted, stretched, and
      repositioned after irrigation and scraping of the stromal bed and the underside
      of the flap. A bandage contact lens was placed, and topical antibiotic and
      corticosteroids were given postoperatively. The dislocated corneal flaps were
      successfully repositioned in both cases. The patient whose dislocated flap was
      repositioned 4 hours after the trauma recovered his uncorrected visual acuity
      (UCVA) of 20/20 1 week after the procedure and had a well-positioned flap with a
      clear interface. The patient who was managed 48 hours after the injury required
      repeat flap repositioning at 10 and 24 days after the initial procedure for
      treatment of persistent folds and striae in the visual axis. His uncorrected
      visual acuity 2 weeks after the third flap repositioning was 20/40 + 2. Diffuse
      lamellar keratitis developed in both patients that resolved with the use of
      topical corticosteroids. CONCLUSION: Laser in situ keratomileusis corneal flaps
      are vulnerable to traumatic dehiscence and dislocation, which can occur more than
      2 years after the procedure.

PMID- 12502954
TI  - Successful regrafting of cultivated corneal epithelium using amniotic membrane as
      a carrier in severe ocular surface disease.
AB  - PURPOSE: Our group performed cultivated allogeneic corneal epithelial
      transplantation in 13 eyes from 11 patients with severe ocular surface disorders.
      After the clinical application of this new surgical treatment, some patients
      experienced epithelial and subepithelial opacities. We applied our procedure
      again in these patients to achieve successful ocular surface reconstruction.
      METHODS: The corneal limbal epithelial cells from donor corneas were cultivated
      for 4 weeks on denuded amniotic membrane (AM) carrier, with 3T3 fibroblast
      coculture and airlifting. The study subjects consisted of 3 patients. At 3 and 12
      months after the first operation, the failed epithelial graft with AM was
      replaced with new allogeneic corneal epithelium cultivated on AM. RESULTS: At 48
      hours after transplantation, the corneal surfaces of the 3 eyes were clear and
      smooth; the entire corneal surfaces were evenly covered with the transplanted
      cultivated corneal epithelium, which did not stain with fluorescein. The ocular
      surface epithelia of these patients are all stable without epithelial defects.
      CONCLUSIONS: We have shown that, in cases where the initially transplanted
      cultivated epithelium becomes opaque, it is possible to repeat the
      transplantation process with new cultivated epithelium on AM.

PMID- 12502955
TI  - Unilateral fungal and mycobacterial keratitis after simultaneous laser in situ
      keratomileusis.
AB  - PURPOSE: To report a case of unilateral fungal and mycobacterial keratitis after
      simultaneous laser in situ keratomileusis (LASIK). METHODS: Case report of a 37
      year-old woman who developed corneal infiltrates located at the flap-stroma
      interface in her left eye 3 weeks after LASIK for myopia. The infiltration
      progressed despite topical antibiotic therapy; therefore, the flap was lifted and
      irrigated with antibiotic solution. Parallel corneal scrapings were taken. The
      patient's condition deteriorated, prompting a lamellar keratoplasty. RESULTS:
      Corneal scrapings demonstrated no growth. Microbiologic cultures of the corneal
      specimen were reported as negative, whereas histopathologic examination disclosed
      fungal filaments. Two months later, the patient presented corneal infiltrates of
      the left eye again. Because the situation worsened despite therapy, a penetrating
      keratoplasty was performed. Histopathologic examination of the host cornea
      revealed no pathogenic species; microbiologic cultures, however, demonstrated
      Mycobacterium chelonae. CONCLUSION: Fungi and M. chelonae are rare and insidious
      causes of infectious keratitis after LASIK. Our case emphasizes the possible
      difficulties in diagnosing and treating a combined or subsequent infection with
      both species.

PMID- 12502956
TI  - In vivo microstructural analysis of the cornea in Scheie's syndrome.
AB  - PURPOSE: To analyze clinical and in vivo microstructural characteristics of both
      corneas of a 13-year-old male subject with Scheie's syndrome and compare the
      observations with the pathologic reports in the literature. METHODS: Standard
      clinical examination and real-time, slit-scanning in vivo confocal microscopy
      were performed and repeated after 1 year. RESULTS: In vivo confocal microscopy
      images at all cellular layers demonstrated brighter intercellular spaces than
      those of normal corneas. Cicatrization of the anterior stroma was identified, and
      the keratocytes of the middle and posterior stroma exhibited markedly altered
      morphology, often round or elliptical in shape, and with clearly demarcated,
      hyporeflective centers. The nerve fibers of the subbasal plexus were somewhat
      more irregular and difficult to distinguish, possibly due to underlying fibrosis.
      CONCLUSIONS: The potential of in vivo confocal microscopy to highlight
      microstructural alterations of the intact human cornea and evaluate such changes
      over time might reduce reliance on histopathologic investigations in such
      conditions and contribute to the ophthalmic management of the
      mucopolysaccharidoses in the future.

PMID- 12502957
TI  - Fungal keratitis associated with vernal keratoconjunctivitis.
AB  - PURPOSE: To report a case of fungal keratitis associated with vernal
      keratoconjunctivitis. CASE REPORT: A 22-year-old man with a history of vernal
      keratoconjunctivitis since October 1999 developed a shield ulcer in the left eye
      in June 2000, which resolved with intensive topical steroid therapy. He presented
      in August 2001 with onset of acute pain, redness, and decreased vision. The
      tarsal conjunctiva in the left eye showed large papillae. The cornea showed a
      white plaque-like lesion with an underlying stromal infiltrate involving the
      upper half of the cornea. The overlying epithelial defect measured 4.5 x 2.5 mm.
      The anterior chamber showed 1+ flare and cells and hypopyon measuring about 1 mm.
      RESULTS: Corneal scrapings were performed for microbiologic investigations.
      Smears of corneal scrapings revealed septate fungal filaments, and the culture
      showed a significant growth of Aspergillus flavus. CONCLUSIONS: Fungal keratitis
      may be associated with vernal keratoconjunctivitis. Though rare, fungal keratitis
      should be considered in the differential diagnosis of infections associated with
      vernal keratoconjunctivitis.

PMID- 12502958
TI  - Annular crystalline keratopathy in association with immunoglobulin therapy for
      pyoderma gangrenosum.
AB  - PURPOSE: To report on a patient with a clinical presentation of annular
      crystalline keratopathy after immunoglobulin therapy for pyoderma gangrenosum.
      METHODS: Case report of a 6-year-old boy with biopsy-proven history of pyoderma
      gangrenosum who had undergone several cycles of systemic immunoglobulin therapy.
      The literature on ocular manifestations associated with pyoderma gangrenosum was
      reviewed. RESULTS: One year after the last cycle, the patient complained of the
      sudden onset of photophobia. Slit-lamp biomicroscopy revealed bilateral symmetric
      crystalline deposits in an annular region of the cornea. Because visual acuity
      was not reduced, specific therapy was not initiated. Symptoms could be reduced by
      the prescription of medical edged filter lenses. CONCLUSIONS: Annular crystalline
      corneal deposits may be associated with immunoglobulin therapy or represent a
      hitherto unknown ocular complication of pyoderma gangrenosum.

PMID- 12502959
TI  - Bilateral corneal ring opacity of unknown origin.
AB  - PURPOSE: To report one case of a bilateral ring-shaped opacity in the mid
      peripheral corneal stroma of unknown origin. METHODS: Case report. RESULTS: The
      authors describe the clinical history and ocular examination of an asymptomatic
      82-year-old woman with a bilateral ring-shaped opacity located in the corneal
      stroma. This rare corneal anomaly was discovered by chance, and the etiology is
      unknown. CONCLUSION: An unusual bilateral corneal abnormality is reported.

PMID- 12502960
TI  - Xylene keratopathy: a case report and review of the literature.
AB  - PURPOSE: To report a case of direct contact xylene-related vacuolar keratopathy.
      METHODS: Interventional case report and review of the literature. RESULTS: Xylene
      keratopathy is a distinct clinical entity characterized by significantly
      decreased visual acuity, increased corneal thickness, and the presence of corneal
      epithelial and stromal vacuoles on a diffuse gray stromal background. The
      vacuoles are diffusely scattered, subtle, and clear on slit-lamp examination.
      Occasionally, white, round, denser areas can also be observed. Xylene keratopathy
      disappeared gradually over 4 weeks with topical steroid treatment and did not
      cause permanent sequelae. CONCLUSIONS: Xylene exposure should be considered as
      possible etiologic agent of vacuolar epithelial and stromal keratopathy. Exposure
      may occur directly as a splash of liquid or through its vapors.

PMID- 12502961
TI  - The study of glaucoma after penetrating keratoplasty.

PMID- 12502962
TI  - Combination therapy for keratitis by the fungus Scedosporium.

PMID- 12502963
TI  - Antifungal effects of cyclosporine A.

PMID- 12502964
TI  - CHIPing soft tissue tumors: will the paradigms be changed?

PMID- 12502965
TI  - Bone marrow biopsy: interpretive guidelines for the surgical pathologist.
AB  - Ideally, the bone marrow core biopsy should be reviewed with knowledge of the
      clinical history, complete blood count, and findings in the peripheral blood and
      bone marrow aspirate smears. However, for a variety of reasons, the pathologist
      may receive the core biopsy and aspirate clot section without all of this
      information. Although this approach is not optimal, a great deal of valuable
      information can be generated from these specimens. Over the past 20 years, there
      has been considerable progress in the fields of flow cytometric analysis,
      immunohistochemistry, and molecular diagnostic studies that can be performed on
      smears or extracted DNA from paraffin embedded tissue. These modalities have
      augmented and refined diagnostic criteria formerly ascertained by light
      microscopy, cytochemistry, and cytogenetics. This is particularly true of some
      myeloid and lymphoreticular neoplasms where a collaborative and multidisciplinary
      approach to the diagnosis has become necessary. Despite this growing complexity
      and dependence on newer methodologies, the traditional role of histopathology in
      evaluating the bone marrow biopsy remains as important as it has been in the
      past. In this review, we focus on contemporary practices and expectations for
      interpreting bone marrow biopsies and clot sections.

PMID- 12502966
TI  - Inhibin immunohistochemical staining: a practical approach for the surgical
      pathologist in the diagnoses of ovarian sex cord-stromal tumors.
AB  - Through a brief introduction of inhibin history, characteristics of the antibody
      against inhibin, and normal tissue distribution of alpha-inhibin expression, this
      comprehensive review focuses on a practical approach to using alpha-inhibin in
      the differential diagnosis of ovarian sex cord-stromal tumors (SCSTs). Alpha
      inhibin has become a most useful immunohistochemical marker of gonadal SCST,
      regardless if the tumors are primary, recurrent, or metastatic. However,
      pathologic diagnosis of individual SCST is still based largely on morphologic
      criteria. Alpha-inhibin immunohistochemical (IHC) staining should be used only
      when a difficult morphologic diagnosis is encountered. In this perspective, alpha
      inhibin and other properly selected markers should be ordered at the same time.
      This is simply because alpha-inhibin is not specific for SCSTs. Caution should be
      exercised in the interpretation of alpha-inhibin-positive cells, because a wide
      variety of primary and metastatic ovarian tumors may contain significant numbers
      of alpha-inhibin-positive stromal cells. As with other immunohistochemical
      stains, a panel of stains and comparison with the corresponding hematoxylin and
      eosin (H&E) slides is necessary, especially when staining patterns and cellular
      localization are in question. The antibody will not help to differentiate tumors
      within the category of SCST. The pattern or the intensity of staining in SCSTs
      does not predict tumor behavior, although there is a tendency of loss of alpha
      inhibin expression in poorly differentiated Sertoli or Sertoli-Leydig cell
      tumors. In cases where metastatic granulosa or Sertoli-Leydig cell tumors are a
      concern, positive alpha-inhibin staining is diagnostic, but a negative result
      does not rule out metastatic disease. Calretinin has been recently recognized as
      a more sensitive, but less specific marker for SCSTs and it may be used to
      recognize an inhibin-negative SCST. In this review, we have listed nine of the
      most commonly encountered clinical scenarios where alpha-inhibin and other
      markers could be used in diagnostic surgical pathology of ovarian tumors.

PMID- 12502967
TI  - The diagnostic value of hepatocyte paraffin antibody 1 in differentiating
      hepatocellular neoplasms from nonhepatic tumors: a review.
AB  - Hepatocyte paraffin-1 (HepPar-1) is a recently developed monoclonal antibody that
      appears to identify an antigen unique to hepatocellular mitochondria. This
      article reviews the use of this new antibody in the differential diagnosis of
      primary hepatocellular neoplasms, cholangiocarcinomas, and carcinomas metastatic
      to the liver. Hepatocyte paraffin-1 appears to be the most sensitive and specific
      positive marker of hepatocellular differentiation, but like any
      immunohistochemical marker, should be interpreted only in the context of the
      overall clinicopathologic picture and as part of a panel of antibodies.

PMID- 12502968
TI  - Pathology and the internet.

PMID- 12502969
TI  - Will xenon be a stranger or a friend?: the cost, benefit, and future of xenon
      anesthesia.

PMID- 12502970
TI  - The alveolar epithelium: suspect or innocent bystander?

PMID- 12502972
TI  - Multicenter randomized comparison of the efficacy and safety of xenon and
      isoflurane in patients undergoing elective surgery.
AB  - BACKGROUND: All general anesthetics used are known to have a negative inotropic
      side effect. Since xenon does not have a negative inotropic effect, it could be
      an interesting future general anesthetic. The aim of this clinical multicenter
      trial was to test the hypothesis of whether recovery after xenon anesthesia is
      faster compared with an accepted, standardized anesthetic regimen and that it is
      as effective and safe. METHOD: A total of 224 patients in six centers were
      included in the protocol. They were randomly assigned to receive either xenon (60
      +/- 5%) in oxygen or isoflurane (end-tidal concentration, 0.5%) combined with
      nitrous oxide (60 +/- 5%). Sufentanil (10 mcirog) was intravenously injected if
      indicated by defined criteria. Hemodynamic, respiratory, and recovery parameters,
      the amount of sufentanil, and side effects were assessed. RESULTS: The recovery
      parameters demonstrated a statistically significant faster recovery from xenon
      anesthesia when compared with isoflurane-nitrous oxide. The additional amount of
      sufentanil did not differ between both anesthesia regimens. Hemodynamics and
      respiratory parameters remained stable throughout administration of both
      anesthesia regimens, with advantages for the xenon group. Side effects occurred
      to the same extent with xenon in oxygen and isoflurane-nitrous oxide. CONCLUSION:
      This first randomized controlled multicenter trial on the use of xenon as an
      inhalational anesthetic confirms, in a large group of patients, that xenon in
      oxygen provides effective and safe anesthesia, with the advantage of a more rapid
      recovery when compared with anesthesia using isoflurane-nitrous oxide.

PMID- 12502973
TI  - Effects of recruitment maneuver on atelectasis in anesthetized children.
AB  - BACKGROUND: General anesthesia is known to promote atelectasis formation. High
      inspiratory pressures are required to reexpand healthy but collapsed alveoli.
      However, in the absence of positive end-expiratory pressure (PEEP), reexpanded
      alveoli collapse again. Using magnetic resonance imaging, the impact of an
      alveolar recruitment strategy on the amount and distribution of atelectasis was
      tested. METHODS: The authors prospectively randomized 24 children who met
      American Society of Anesthesiologists physical status I or II criteria, were aged
      6 months-6 yr, and were undergoing cranial magnetic resonance imaging into three
      groups. After anesthesia induction, in the alveolar recruitment strategy (ARS)
      group, an alveolar recruitment maneuver was performed by manually ventilating the
      lungs with a peak airway pressure of 40 cm H2O and a PEEP of 15 cm H2O for 10
      breaths. PEEP was then reduced to and kept at 5 cm H2O. The continuous positive
      airway pressure (CPAP) group received 5 cm H2O of continuous positive airway
      pressure without recruitment. The zero end-expiratory pressure (ZEEP) group
      received neither PEEP nor the recruitment maneuver. All patients breathed
      spontaneously during the procedure. After cranial magnetic resonance imaging,
      thoracic magnetic resonance imaging was performed. RESULTS: The atelectatic
      volume (median, first and third standard quartiles) detected in the ZEEP group
      was 1.25 (0.75-4.56) cm3 in the right lung and 4.25 (3.2-13.9) cm3 in the left
      lung. The CPAP group had 9.5 (3.1-23.7) cm3 of collapsed lung tissue in the right
      lung and 8.8 (5.3-28.5) cm3 in the left lung. Only one patient in the ARS group
      presented an atelectasis of less than 2 cm3. An uneven distribution of the
      atelectasis was observed within each lung and between the right and left lungs,
      with a clear predominance of the left basal paradiaphragmatic regions.
      CONCLUSION: Frequency of atelectasis was much less following the alveolar
      recruitment strategy, compared with children who did not have the maneuver
      performed. The mere application of 5 cm H2O of CPAP without a prior recruitment
      did not show the same treatment effect and showed no difference compared to the
      control group without PEEP.

PMID- 12502974
TI  - Laryngoscopic intubation: learning and performance.
AB  - BACKGROUND: Many healthcare professionals are trained in direct laryngoscopic
      tracheal intubation (LEI), which is a potentially lifesaving procedure. This
      study attempts to determine the number of successful LEI exposures required
      during training to assure competent performance, with special emphasis on
      defining competence itself. METHODS: Analyses were based on a longitudinal study
      of novices under training conditions in the operating room. The progress of 438
      LEIs performed by the 20 nonanesthesia trainees was monitored by observation and
      videotape analysis. Eighteen additional LEIs were performed by experienced
      anesthesiologists to define the standard. A generalized linear, mixed-modelling
      approach was used to identify key aspects of effective training and performance.
      The number of tracheal intubations that the trainees were required to perform
      before acquiring expertise in LEI was estimated. RESULTS: Subjects performed
      between 18 and 35 laryngoscopic intubations. However, statistical modeling
      indicates that a 90% probability of a "good intubation" required 47 attempts.
      Proper insertion and lifting of the laryngoscope were crucial to "good" or
      "competent" performance of LEI. Traditional features, such as proper head and
      neck positions, were found to be less important under the study conditions.
      CONCLUSIONS: This study determined that traditional LEI teaching for
      nonanesthesia personnel using manikin alone is inadequate. A reevaluation of
      current standards in LEI teaching for nonanesthesia is required.

PMID- 12502975
TI  - Optimal oxygen concentration during induction of general anesthesia.
AB  - BACKGROUND: The use of 100% oxygen during induction of anesthesia may produce
      atelectasis. The authors investigated how different oxygen concentrations affect
      the formation of atelectasis and the fall in arterial oxygen saturation during
      apnea. METHODS: Thirty-six healthy, nonsmoking women were randomized to breathe
      100, 80, or 60% oxygen for 5 min during the induction of general anesthesia.
      Ventilation was then withheld until the oxygen saturation, assessed by pulse
      oximetry, decreased to 90%. Atelectasis formation was studied with computed
      tomography. RESULTS: Atelectasis in a transverse scan near the diaphragm after
      induction of anesthesia and apnea was 9.8 +/- 5.2 cm2 (5.6 +/- 3.4% of the total
      lung area; mean +/- SD), 1.3 +/- 1.2 cm2 (0.6 +/- 0.7%), and 0.3 +/- 0.3 cm2 (0.2
      +/- 0.2%) in the groups breathing 100, 80, and 60% oxygen, respectively (P <
      0.01). The corresponding times to reach 90% oxygen saturation were 411 +/- 84,
      303 +/- 59, and 213 +/- 69 s, respectively (P < 0.01). CONCLUSION: During routine
      induction of general anesthesia, 80% oxygen for oxygenation caused minimal
      atelectasis, but the time margin before unacceptable desaturation occurred was
      significantly shortened compared with 100% oxygen.

PMID- 12502976
TI  - Differential effects of propofol and sevoflurane on heart rate variability.
AB  - BACKGROUND: Propofol is reported to reduce both sympathetic and parasympathetic
      tone; however, it is not clear whether the changes in heart rate variability are
      associated with depth of anesthesia. The purposes of the present study were (1)
      to evaluate the changes in heart rate variability at different depths of hypnosis
      and (2) to compare the effects of propofol on heart rate variability with that of
      sevoflurane. METHODS: Thirty patients were randomly allocated into the propofol
      or sevoflurane for induction of anesthesia. The depth of hypnosis was monitored
      by the Bispectral Index (BIS). Spectral analysis of heart rate variability using
      a maximum-entropy method resulted in a characteristic power spectrum with two
      main regions, a high frequency (HF) and a low frequency (LF). Hemodynamics,
      entropy, LF, HF, and LF/HF were monitored when the patients were awake and after
      induction of anesthesia. RESULTS: Both propofol and sevoflurane decreased blood
      pressure in a BIS-dependent manner, whereas heart rate showed no significant
      changes during the study period. In the propofol group, entropy and HF decreased
      with a reduction in the BIS value. Although LF decreased after induction of
      anesthesia, propofol caused no further decrease in LF in spite of a reduction in
      the BIS value. In the sevoflurane group, LF decreased with a reduction in the BIS
      value. Entropy and HF decreased after induction of anesthesia (BIS at 80);
      however, no further decreases were observed in spite of a reduction in the BIS
      value. CONCLUSIONS: Induction of anesthesia with propofol decreased blood
      pressure, entropy, and HF in a BIS-dependent manner, indicating that propofol
      reduces cardiac parasympathetic tone depending on the depth of hypnosis.
      Conversely, sevoflurane did not show the BIS-dependent decreases in heart rate,
      blood pressure, HF, and entropy, indicating that sevoflurane has little or no
      effect on cardiac parasympathetic tone.

PMID- 12502977
TI  - Developmental changes of laryngeal dimensions in unparalyzed, sedated children.
AB  - BACKGROUND: Knowledge of the influence of age on laryngeal dimensions is
      essential for all practitioners whose interest is the pediatric airway. Early
      cadaver studies documented that the larynx is conically shaped, with the apex of
      the cone caudally positioned at the nondistensible cricoid cartilage. These
      dimensions change during childhood, as the larynx assumes a more cylindrical
      shape. The authors analyzed laryngeal dimensions during development to determine
      if this relationship continues in unparalyzed children in whom laryngeal muscles
      are tonically active. The authors determined the relationships between the vocal
      cord, sub-vocal cord, and cricoid ring dimensions and the influence of age on
      these relationships. METHODS: Infants and children undergoing magnetic resonance
      imaging with propofol sedation had determinations of the transverse and anterior
      posterior (AP) dimensions of the larynx at the most cephalad level of the larynx
      (vocal cords) and the most caudad level (cricoid). Most patients had an
      additional measurement (sub-vocal cord) at a level between the vocal cords and
      the cricoid ring. Relationships were obtained by plotting age against laryngeal
      dimensions and the ratio of laryngeal dimensions at different levels within the
      larynx. RESULTS: The authors measured transverse and AP laryngeal dimensions in
      99 children, aged 2 months-13 yr. The relationship between the transverse and AP
      dimensions at all levels of the larynx did not change during development.
      Transverse and AP dimensions increased linearly with age at all levels of the
      larynx. In all children studied, the narrowest portion of the larynx was the
      transverse dimension at the level of the vocal cords. Transverse dimensions
      increased linearly in a caudad direction through the larynx ( P< 0.001), while AP
      dimensions did not change relative to laryngeal level. The shape of the cricoid
      ring did not change throughout childhood. CONCLUSIONS: In sedated, unparalyzed
      children, the narrowest portions of the larynx are the glottic opening (vocal
      cord level) and the immediate sub-vocal cord level, and there is no change in the
      relationships of these dimensions relative to cricoid dimensions throughout
      childhood.

PMID- 12502978
TI  - Difference in risk factors for postoperative nausea and vomiting.
AB  - BACKGROUND: It is commonly stated that risk factors for postoperative nausea are
      the same as for vomiting. The authors designed a prospective study to identify
      and differentiate the risk factors for postoperative nausea and vomiting in
      various surgical populations in a clinical audit setting. METHODS: The study
      included 671 consecutive surgical inpatients, aged 15 yr or more, undergoing
      various procedures. The study focused on postoperative nausea visual analog scale
      scores every 4 h and vomiting episodes within 72 h. Both vomiting and retching
      were considered as emetic events. Patient-, anesthesia-, and surgery-related
      variables that were considered to have a possible effect on the proportion of
      patients experiencing postoperative nausea and/or vomiting were examined. The
      bivariate Dale model for binary correlated outcomes was used to identify
      selectively the potential risk factors of postoperative nausea and vomiting.
      RESULTS: Among the 671 patients in the study, 126 (19%) reported one or more
      episodes of nausea, and 66 patients (10%) suffered one or more emetic episodes
      during the studied period. There was a highly significant association between the
      two outcomes. Some risk factors were predictive of both nausea and vomiting
      (female gender, nonsmoking status, and general anesthesia). History of migraine
      and type of surgery were mainly responsible for nausea but not for vomiting. The
      predictive effect of risk factors was controlled for postoperative pain and
      analgesic drugs. CONCLUSION: This study shows that differences exist in risk
      factors of postoperative nausea and vomiting. These could be explained by
      differences in the physiopathology of the two symptoms.

PMID- 12502979
TI  - Hypothermia and the approximate entropy of the electroencephalogram.
AB  - BACKGROUND: The electroencephalogram is commonly used to monitor the brain during
      hypothermic cardiopulmonary bypass and circulatory arrest. No quantitative
      relationship between the electroencephalogram and temperature has been
      elucidated, even though the qualitative changes are well known. This study was
      undertaken to define a dose-response relationship for hypothermia and the
      approximate entropy of the electroencephalogram. METHODS: The
      electroencephalogram was recorded during cooling and rewarming in 14 patients
      undergoing hypothermic cardiopulmonary bypass and circulatory arrest. Data were
      digitized at 128 Hz, and approximate entropy was calculated from 8-s intervals.
      The dose-response relationship was derived using sigmoidal curve-fitting
      techniques, and statistical analysis was performed using analysis of variance
      techniques. RESULTS: The approximate entropy of the electroencephalogram changed
      in a sigmoidal fashion during cooling and rewarming. The midpoint of the curve
      averaged 24.7 degrees C during cooling and 28 degrees C (not significant) during
      rewarming. The temperature corresponding to 5% entropy (T 0.05 ) was 18.7 degrees
      C. The temperature corresponding to 95% entropy (T 0.95 ) was 31.3 degrees C
      during cooling and 38.2 degrees C during rewarming ( P < 0.02). CONCLUSIONS:
      Approximate entropy is a suitable analysis technique to quantify the
      electroencephalographic changes that occur with cooling and rewarming. It
      demonstrates a delay in recovery that is of the same magnitude as that seen with
      conventional interpretation of the analog electroencephalogram and extends these
      observations over a greater range of temperatures.

PMID- 12502980
TI  - Parental presence during induction of anesthesia: physiological effects on
      parents.
AB  - BACKGROUND: The authors conducted a randomized controlled trial to determine
      whether parental presence during induction of anesthesia (PPIA) is associated
      with parental physiologic and behavioral manifestations of stress. METHODS:
      Children and their parents (N = 80) were randomly assigned to one of three
      groups: (1) PPIA; (2) PPIA plus 0.5 mg/kg oral midazolam; and (3) control (no
      PPIA or midazolam). The effect of the group assignment on parental heart rate
      (HR), parental blood pressure, and parental skin conductance level (SCL) were
      assessed. Both parental HR and parental SCL were monitored continually. Anxiety
      of the parent and child was also assessed. RESULTS: Parental HR increased from
      baseline until the induction of anesthesia (P = 0.001). A group-by-time effect (
      P= 0.005) was also found. That is, throughout the induction period there were
      several time points at which parents in the two PPIA groups had a significantly
      higher HR than did parents in the control group (P < 0.05). Similarly, SCL was
      found to increase in all parents from baseline until induction of anesthesia (P =
      0.001). Significant group differences in SCL changes over time were found as well
      (P = 0.009). State anxiety and blood pressure following induction of anesthesia
      did not differ significantly between groups ( P= nonsignificant). Examination of
      parental Holter data revealed no rhythm abnormalities and no electrocardiogram
      changes indicating ischemia. CONCLUSIONS: The authors found that PPIA is
      associated with increased parental HR and SCL. However, no increased incidence of
      electrocardiogram abnormalities were found in parents present during induction of
      anesthesia.

PMID- 12502981
TI  - Performance of target-controlled sufentanil infusion in obese patients.
AB  - BACKGROUND: Because obesity might affect pharmacokinetic parameters, the authors
      evaluated the accuracy of target-controlled sufentanil infusion in morbidly obese
      patients using a pharmacokinetic model usually applied to a normal-weight
      population. METHODS: Target-controlled propofol and sufentanil coinfusions were
      administered to 11 morbidly obese patients (body mass index: 45.0 +/- 6.5 kg/m2 )
      undergoing laparoscopic gastroplasty. The target plasma propofol concentration
      was 3 micro g/ml. The effect-site sufentanil target concentration was initially
      0.4 ng/ml but was modified during surgery as a function of blood pressure and
      heart rate. Plasma sufentanil concentrations were measured from the onset of
      infusion until 24 h after its termination. The predicted sufentanil target
      concentrations were calculated by STANPUMP software. Intrasubject data analyzed
      included calculation of performance error, median performance error, median
      absolute performance error, divergence, and wobble. Pharmacokinetic analysis was
      performed using a nonlinear mixed effect model. RESULTS: Applied sufentanil
      target concentrations ranged from 0.3 to 0.65 ng/ml. The mean +/- SD plasma
      sufentanil concentration measured during spontaneous ventilation was 0.13 +/-
      0.03 ng/ml. Median performance error (range) was -13% (-42 to 36%). Median
      absolute performance error was 26% (8-44%) during infusion and 17% (12-59%) for
      the 24 h after its completion. The pharmacokinetic sets used slightly
      overpredicted the concentrations, with a median divergence of -3.4% (-10.2 to
      3.1%) during infusion. For body mass index greater than 40, the overestimation of
      plasma sufentanil concentrations was greater. A two-compartment model with
      proportional error for interindividual variability best fitted the data. The
      residual variability was modeled as an additive (0.016 ng/ml) or proportional
      error (23%). Clearance, central volume of distribution, intercompartmental
      clearance, and peripheral volume of distribution (coefficient of variation) were
      1.27 l/min (23%), 37.1 l (20%), 0.87 l/min (44%), and 92.7 l (22%), respectively.
      CONCLUSION: The pharmacokinetic parameter set derived from a normal-weight
      population accurately predicted plasma sufentanil concentrations in morbidly
      obese patients.

PMID- 12502982
TI  - Halogenated anesthetics reduce interleukin-1beta-induced cytokine secretion by
      rat alveolar type II cells in primary culture.
AB  - BACKGROUND: Alveolar epithelial type II (AT II ) cells participate in the
      intraalveolar cytokine network by secreting cytokines and are widely exposed to
      volatile anesthetics during general anesthesia. The aim of the current study was
      to evaluate the effects of halothane, enflurane, and isoflurane on rat AT II cell
      cytokine secretions in AT II primary cell cultures. METHODS: Alveolar epithelial
      type II primary cell cultures were obtained from adult rat lungs. AT II cells
      were stimulated by recombinant murine interleukin-1beta (rmIL-1beta) to mimic an
      inflammatory response, and immediately exposed for various duration to different
      concentration of halothane, enflurane, or isoflurane. Interleukin-6, macrophage
      inflammatory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1)
      protein concentrations were then measured in cell culture supernatants.
      Recombinant mIL-1beta-stimulated AT II cells exposed to air served as control.
      RESULTS: Halothane, isoflurane, and enflurane (1 minimum alveolar concentration
      [MAC], 4 h) decreased rmIL-1beta-stimulated AT II cell secretions of interleukin
      6, MIP-2, and MCP-1, but did not modify total protein secretion. Halothane
      exposure decreased rmIL-1beta-stimulated AT II cell secretions of interleukin-6,
      MIP-2, and MCP-1 in a dose- and time-dependent manner. Total protein
      concentrations remained unchanged except AT II 1.5 MAC of halothane, and no
      cytotoxic effect could be evidenced by lactate dehydrogenase release. These
      effects were transient as rmIL-1beta-stimulated AT II cell secretions of
      interleukin-6 and MIP-2 progressively reached control values between 4 and 24 h
      after the end of halothane exposure. However, MCP-1 inhibition persisted until 24
      h. rmIL-1beta-induced MIP-2 and tumor necrosis factor-alpha mRNA expression were
      decreased by 36 and 24%, respectively, after halothane exposure. CONCLUSIONS: The
      current study shows that exposure of rmIL-1beta-stimulated AT II cells to
      volatile anesthetics reversibly alters their cytokine secretion. Therefore,
      volatile anesthesia, by modulating pulmonary epithelial cell secretion of
      inflammatory cytokines, might affect the lung inflammatory response.

PMID- 12502983
TI  - Systemic inflammation leads to resistance to atracurium without increasing
      membrane expression of acetylcholine receptors.
AB  - BACKGROUND: Systemic inflammation may be associated with resistance to
      nondepolarizing neuromuscular blocking drugs, the mechanisms of which are,
      however, uncharacterized. The authors therefore investigated the pharmacodynamics
      of atracurium and its relation to the expression of nicotinic acetylcholine
      receptors and alpha1 -acid glycoprotein in a rat model of systemic inflammation.
      METHODS: To induce a systemic inflammation, male CD rats received 56 mg/kg
      corynebacterium parvum intravenously. On days 2, 4, 6, 8, 10, 12, 14, or 16 after
      infection, neuromuscular transmission was measured. The individual effective dose
      of atracurium was determined, followed by an atracurium infusion at a rate to
      establish a steady state neuromuscular block of 50%. Total and unbound plasma
      concentrations of atracurium for 50% paralysis were measured using high
      performance liquid chromatography. Acetylcholine receptors were quantitated using
      125I-alpha-bungarotoxin. alpha1 -Acid glycoprotein concentrations in the serum
      were measured using a competitive chemiluminescence immunoassay. RESULTS: The
      effective dose of atracurium was increased on days 4, 6, and 8. Total atracurium
      plasma concentrations at 50% neuromuscular paralysis were increased on days 4, 6,
      8, and 10, with a peak at day 8 (8.0 +/- 1.3 micro g/ml) compared with control
      rats (4.23 +/- 0.82 micro g/ml). The alpha1 -acid glycoprotein concentrations
      were increased between days 2 and 10, with a peak on day 4 (6.52 +/- 1.45 mg/ml),
      and recovered to control values (0.61 +/- 0.33 mg/ml) on day 12. Unbound plasma
      concentrations of atracurium to achieve 50% depression, as well as the expression
      of acetylcholine receptors, did not differ between groups. CONCLUSION: Resistance
      to atracurium during corynebacterium parvum-induced systemic inflammation is due
      to increased drug binding to alpha1 -acid glycoprotein and is unrelated to
      changes in acetylcholine receptor expression.

PMID- 12502984
TI  - Isoflurane pretreatment inhibits lipopolysaccharide-induced inflammation in rats.
AB  - BACKGROUND: Previous studies have indicated that volatile anesthetic pretreatment
      protects cells from inflammation; therefore, the authors hypothesized that
      pretreatment with isoflurane may attenuate the hemodynamic and pathologic changes
      to the vasculature that are associated with inflammation. METHODS: Rats received
      intravenous lipopolysaccharide or saline placebo with and without pretreatment
      with isoflurane (1.4% for 30 min immediately before lipopolysaccharide). Mean
      arterial pressure (MAP) and response to endothelium-dependent (acetylcholine) and
      -independent (sodium nitroprusside) vasodilators were assessed hourly for 6 h.
      Tumor necrosis factor-alpha concentrations, arterial blood gases, and vascular
      histology were also determined. RESULTS: Lipopolysaccharide decreased MAP and
      vasodilation to acetylcholine and sodium nitroprusside. Lipopolysaccharide also
      caused acidosis, endothelial swelling, and endothelial detachment from the smooth
      muscle. Isoflurane pretreatment prevented the decrease in MAP for 5 h and
      attenuated the decrease at 6 h. Pretreatment increased the vasodilation to
      acetylcholine in lipopolysaccharide rats to control concentrations but had no
      effect on sodium nitroprusside. In control rats, isoflurane pretreatment
      increased the response to acetylcholine and sodium nitroprusside but had no
      effect on MAP. Isoflurane pretreatment prevented the acidosis and endothelial
      damage to mesenteric and aortic vessels, and attenuated the increase in tumor
      necrosis factor-alpha associated with lipopolysaccharide-induced inflammation.
      CONCLUSION: Pretreatment with 30 min of isoflurane attenuated the decrease in MAP
      and endothelium-dependent vasodilation, the acidosis, the increase in tumor
      necrosis factor-alpha, and the damage to the vascular endothelium associated with
      lipopolysaccharide-induced inflammation in rats. This study suggests that
      isoflurane pretreatment may protect the vasculature during inflammation.

PMID- 12502985
TI  - Hemodynamic and cardiac electrophysiologic effects of lidocaine-bupivacaine
      mixture in anesthetized and ventilated piglets.
AB  - BACKGROUND: The sensory blockade induced by a lidocaine-bupivacaine mixture
      combines the faster onset of lidocaine and the longer duration of bupivacaine.
      The current study compared the effects of large doses lidocaine (16 mg/kg),
      bupivacaine (4 mg/kg), and a mixture of 16 mg/kg lidocaine-4 mg/kg bupivacaine on
      hemodynamic and cardiac electrophysiologic parameters in anesthetized and
      ventilated piglets. METHODS: After carotid artery cannulation, a double
      micromanometer measured mean aortic pressure, left ventricular end diastolic
      pressure, and the first derivative of left ventricular pressure.
      Electrocardiogram recording and a bipolar electrode catheter measured RR, PQ,
      QRS, QT C, JT C, AH, and HV intervals. Lidocaine, bupivacaine, or the mixture was
      administered intravenously over 30 s, and studied parameters were measured
      throughout 30 min. RESULTS: Mean aortic pressure decreased in all groups ( P <
      0.05). The first derivative of left ventricular pressure was decreased in all
      groups ( P < 0.001) but to a greater extent with the mixture compared with
      lidocaine ( P < 0.04). RR, QT C, and JT C intervals were similarly increased in
      all groups ( P < 0.05). In all groups, PQ, AH, HV, and QRS intervals were widened
      ( P < 0.001). The lengthening of PQ was greater with bupivacaine ( P < 0.02). The
      lengthening of AH was greater and delayed with bupivacaine compared with
      lidocaine ( P < 0.03). The lengthening of HV and the widening of QRS were greater
      and delayed with bupivacaine ( P < 0.01). The widening of QRS was greater with
      the mixture than with lidocaine ( P < 0.01). CONCLUSIONS: The alterations of
      ventricular conduction parameters are greater with 4 mg/kg bupivacaine than with
      a mixture of 16 mg/kg lidocaine-4 mg/kg bupivacaine, whereas the hemodynamic
      parameters are similarly altered.

PMID- 12502986
TI  - Inhibitory effects of etomidate and ketamine on adenosine triphosphate-sensitive
      potassium channel relaxation in canine pulmonary artery.
AB  - BACKGROUND: The authors recently demonstrated that etomidate and ketamine
      attenuated endothelium-dependent pulmonary vasorelaxation mediated by nitric
      oxide and Ca -activated K + channels. In the current study, they tested the
      hypothesis that these intravenous anesthetics inhibit pulmonary vasorelaxation
      mediated by adenosine triphosphate-sensitive potassium (K + ATP ) channel
      activation. METHODS: Endothelium intact and denuded pulmonary arterial rings were
      suspended in organ chambers for isometric tension recording. The effects of
      etomidate (5 x 10(-6) and 5 x 10(-5) m) and ketamine (5 x 10(-5) and 10(-4) m) on
      vasorelaxation responses to lemakalim (K + ATP channel activator), prostacyclin,
      and papaverine were assessed in phenylephrine-precontracted rings. The effect of
      cyclooxygenase inhibition with indomethacin was assessed in some protocols.
      RESULTS: Etomidate (5 x 10(-6) m) only inhibited the vasorelaxant response to
      lemakalim in endothelium intact rings, whereas a higher concentration of
      etomidate (5 x 10(-5) m) inhibited relaxation in both intact and endothelium
      denuded rings. Pretreatment with indomethacin abolished the endothelium-dependent
      attenuation of lemakalim-induced relaxation caused by etomidate. Ketamine (5 x
      10(-5) and 10(-5) m) inhibited the relaxation response to lemakalim to the same
      extent in both endothelium-intact and -denuded rings, and this effect was not
      prevented by indomethacin pretreatment. Etomidate and ketamine had no effect on
      the relaxation responses to prostacyclin or papaverine. CONCLUSIONS: These
      results indicate that etomidate, but not ketamine, attenuates the endothelium
      dependent component of lemakalim-induced pulmonary vasorelaxation an inhibitory
      effect on the cyclooxygenase pathway. Both anesthetics inhibit K + ATP -mediated
      pulmonary vasorelaxation a direct effect on pulmonary vascular smooth muscle.

PMID- 12502987
TI  - Isoflurane sensitizes the cardiac sarcolemmal adenosine triphosphate-sensitive
      potassium channel to pinacidil.
AB  - BACKGROUND: Cardioprotective effects of isoflurane are partially mediated by the
      sarcolemmal adenosine triphosphate-sensitive potassium (sarcK ATP ) channel. The
      authors tested the hypothesis that isoflurane sensitizes sarcK ATP channels to a
      potassium channel opener, pinacidil, adenosine- and phospholipid-mediated
      pathways. METHODS: Activation by pinacidil of the K ATP current (I KATP ) was
      monitored in guinea pig ventricular myocytes at 0.5 and 5 mm intracellular ATP in
      the whole cell configuration of the patch clamp technique. The sensitization
      effect was evaluated by pretreating each myocyte with isoflurane (0.57 +/- 0.04
      mm) before application of pinacidil (5 micro m) in the continued presence of the
      anesthetic. To investigate whether intracellular signaling pathways may be
      involved in isoflurane sensitization, the authors used the adenosine receptor
      antagonist theophylline (100 micro m) and the phosphatidylinositol kinase
      inhibitor wortmannin (100 micro m). RESULTS: The density of pinacidil-activated I
      KATP was higher at 0.5 mm ATP (20.7 +/- 3.2 pA/pF) than at 5 mm ATP (2.0 +/- 0.3
      pA/pF). At 0.5 mm ATP, pretreatment with isoflurane caused an increase in density
      of pinacidil-activated I KATP (42.4 +/- 6.2 pA/pF) and accelerated the rate of
      current activation (from 5.4 +/- 1.2 to 39.0 +/- 7.9 pA. pF(-1). min(-1) ).
      Theophylline attenuated current activation by pinacidil (9.4 +/- 3.9 pA/pF) and
      abolished the sensitization effect of isoflurane on I KATP (10.0 +/- 2.5 pA/pF).
      Wortmannin did not alter pinacidil activation of I KATP (13.2 +/- 1.7 pA/pF) but
      prevented sensitization by isoflurane (15.8 +/- 4.5 pA/pF). CONCLUSIONS: These
      results suggest that isoflurane increases sensitivity of cardiac sarcK ATP
      channels to the potassium channel opener pinacidil. Blockade of adenosine
      receptors or phosphatidylinositol kinases abolishes the sensitization effect,
      suggesting that the adenosine and phospholipid signaling pathways may be involved
      in the actions by isoflurane.

PMID- 12502988
TI  - Ketamine differentially blocks sensory afferent synaptic transmission in medial
      nucleus tractus solitarius (mNTS).
AB  - BACKGROUND: Ketamine increases blood pressure and heart rate by unknown
      mechanisms, but studies suggest that an intact central nervous system and
      arterial baroreceptors are required. In the brain stem, medial nucleus tractus
      solitarius receives afferents from nodose neurons that initiate cardiovascular
      autonomic reflexes. Here, the authors assessed ketamine actions on afferent
      medial nucleus tractus solitarius synaptic transmission. METHODS: Ketamine was
      applied to horizontally sliced brain stems. Solitary tract (ST) stimulation
      evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus
      solitarius neurons. Capsaicin (200 nm) block of ST eEPSCs sorted neurons into
      sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to
      the peripheral vagal trunk activated afferent action potentials in sensory
      neurons classified by conduction velocities and capsaicin. RESULTS: Ketamine
      potently (10-100 mciro m) blocked small, ST-evoked -methyl-d-aspartate synaptic
      currents found only in a subset of capsaicin-resistant neurons (6 of 12).
      Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced
      synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin
      resistant neurons (P < 0.005; n = 11 and 11). Spontaneous EPSCs using non- 
      methyl-d-aspartate receptors were insensitive even to 1-3 mm ketamine, suggesting
      that ST responses were blocked presynaptically. Similarly, ketamine blocked C
      type action potential conduction at lower concentrations than A-type nodose
      sensory neurons. CONCLUSION: The authors conclude that ketamine inhibits
      postsynaptic -methyl-d-aspartate receptors and presynaptic afferent processes in
      medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type),
      unmyelinated afferents are significantly more susceptible to block than capsaicin
      resistant (A-type), myelinated afferents. This differentiation may be related to
      tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful
      arterial baroreflexes effects, these differential actions may contribute to
      ketamine-induced cardiovascular dysfunction.

PMID- 12502989
TI  - Pharmacokinetic-pharmacodynamic modeling of rocuronium in case of a decreased
      number of acetylcholine receptors: a study in myasthenic pigs.
AB  - BACKGROUND: In myasthenic patients, the sensitivity for nondepolarizing relaxants
      is increased and the time course of effect is prolonged due to a reduced number
      of functional acetylcholine receptors at the neuromuscular junction. The authors
      investigated both the performance of the link model proposed by Sheiner and a
      pharmacodynamic-pharmacokinetic model taking into account the number of unbound
      acetylcholine receptors in myasthenic pigs. METHODS: After obtaining the approval
      of the Animal Experiments Committee of their institution, the authors studied
      eight myasthenic pigs and eight control pigs. Myasthenia gravis was induced by
      injecting Torpedo acetylcholine receptors in weeks 1 and 4. On the day of the
      experiments, the pigs were anesthetized and intubated, and the appropriate
      muscles and nerves were prepared for the measurements. Rocuronium was
      administered by infusion to reach 90% twitch height block. Arterial blood was
      sampled during onset and offset of effect, and the plasma concentration of
      rocuronium was measured with high-performance liquid chromatography. Plasma
      concentration-time effect data were analyzed using two different pharmacokinetic
      pharmacodynamic models, the link model according to Sheiner and a pharmacokinetic
      pharmacodynamic model taking into account the unbound receptor concentration.
      Muscles were removed after the experiment for laboratory analysis of the
      acetylcholine receptor concentration. RESULTS: All eight pigs of the myasthenic
      group developed clinical signs of myasthenia gravis (muscle weakness) and showed
      increased sensitivity toward rocuronium. Pharmacokinetic modeling revealed no
      significant differences between myasthenic and control pigs. In pharmacokinetic
      pharmacodynamic analysis, visual inspection as well as the Akaike Information
      Criterion (3,605 3,769) and the residual SD (3.2 3.6%) revealed a better fit for
      the unbound receptor model in myasthenic animals compared to the Sheiner model.
      Pharmacokinetic-pharmacodynamic analysis with the unbound receptor model
      demonstrated a decreased EC50 of 0.27 micro m (ranging from 0.17 to 0.59 micro m)
      compared to 2.71 micro m (ranging from 2.42 to 4.43 micro m) in control animals.
      The results of the Sheiner pharmacokinetic-pharmacodynamic analysis were in the
      same range. Both the laboratory analysis and pharmacokinetic-pharmacodynamic
      modeling showed a decrease in receptor concentration of more than 75%.
      CONCLUSION: Both the Sheiner model and the unbound receptor model may be used to
      fit plasma concentration-effect data of rocuronium in pigs. The unbound receptor
      concentration model, however, can explain the observed differences in the time
      course of effect, based on receptor concentration.

PMID- 12502990
TI  - Continuous interscalene analgesia with ropivacaine 2 mg/ml after major shoulder
      surgery.
AB  - BACKGROUND: In this open, randomized study, the pharmacokinetics, clinical
      efficacy, and safety of a 48-h continuous interscalene infusion of 2 mg/ml
      ropivacaine for postoperative pain relief were investigated in patients
      undergoing open major shoulder surgery. METHODS: An initial interscalene block
      with 30 ml ropivacaine, 7.5 mg/ml (225 mg), was performed. After completion of
      interscalene block, all patients (n = 24) received general anesthesia, and 6 h
      after interscalene block, a 48-h continuous interscalene infusion of 12 or 18
      mg/h using 2 mg/ml ropivacaine was started. Total and unbound plasma
      concentrations of ropivacaine and 2.6-pipecoloxylidide (PPX; a major active
      metabolite) were determined during and up to 6 h after the interscalene infusion.
      Postoperative pain at rest was assessed by a visual analog scale. Supplementary
      analgesics and adverse events were recorded. RESULTS: Plasma concentrations of
      total and unbound ropivacaine were proportional to the total dose. At the end of
      the interscalene infusion of 9 ml/h, the mean +/- SD plasma concentrations of
      total and unbound ropivacaine were 1.40 +/- 0.54 and 0.03 +/- 0.01 mg/l,
      respectively, and of total and unbound PPX were 0.70 +/- 0.38 and 0.30 +/- 0.20
      mg/l, respectively. Plasma concentrations of unbound ropivacaine and unbound PPX,
      added together, remained well below threshold levels for systemic central nervous
      system toxicity. There were no significant differences between the groups for
      postoperative pain (median maximum of about 20 mm on the visual analog scale in
      both groups), analgesic consumption, or quality of pain relief assessed by the
      patient. No signs or symptoms of systemic local anesthetic toxicity were
      observed. CONCLUSION: A 48-h continuous interscalene infusion of 6 or 9 ml/h
      ropivacaine, 2 mg/ml, started 6 h after an initial interscalene block of 30 ml
      ropivacaine, 7.5 mg/ml, provided satisfactory postoperative pain relief after
      major shoulder surgery and was well tolerated. Unbound plasma concentrations of
      ropivacaine and PPX remained well below threshold levels for systemic central
      nervous toxicity.

PMID- 12502991
TI  - Effects of preemptive analgesia on pain and cytokine production in the
      postoperative period.
AB  - BACKGROUND: The postoperative period is associated with increased production of
      proinflammatory cytokines, which are known to augment pain sensitivity, among
      other effects. In a previous study, the authors found that patients treated with
      patient-controlled epidural analgesia (PCEA) exhibited attenuated proinflammatory
      cytokine response in the postoperative period. In the present study, the authors
      examined whether preemptive analgesia continued with PCEA may further attenuate
      the proinflammatory cytokine response and reduce pain sensitivity in the
      postoperative period. They compared cytokine production in two groups of
      patients, one receiving PCEA, the other receiving preemptive epidural analgesia
      continued by PCEA. METHODS: Female patients hospitalized for transabdominal
      hysterectomy were randomly assigned to one of two pain management techniques:
      PCEA or preemptive epidural analgesia followed by PCEA (PA + PCEA). Postoperative
      pain was assessed using the visual analog scale. Blood samples were collected
      before, 24, 48, and 72 h following surgery. Production of the following cytokines
      was assessed in stimulated peripheral blood mononuclear cells: interleukin (IL)
      1beta, tumor necrosis factor alpha, IL-6, IL-1ra, IL-10, and IL-2. RESULTS:
      Patients of the PA + PCEA group exhibited lower pain scores throughout the 72 h
      postoperatively, compared with patients of the PCEA group. In patients of the PA
      + PCEA group in the postoperative period, production of IL-1beta, IL-6, IL-1ra,
      and IL-10 was significantly less elevated, while IL-2 production was
      significantly less suppressed. CONCLUSIONS: Proinflammatory cytokines are key
      mediators of illness symptoms, including hyperalgesia. The present results
      suggest that preemptive epidural analgesia is associated with reduced
      postoperative pain and attenuated production of proinflammatory cytokines.

PMID- 12502992
TI  - Preoperative cardiac events in elderly patients with hip fracture randomized to
      epidural or conventional analgesia.
AB  - BACKGROUND: Perioperative myocardial ischemia occurs in 35% of unselected elderly
      patients undergoing hip fracture surgery. Perioperative epidural analgesia may
      reduce the incidence of adverse cardiac events. METHODS: The effect of early
      administration of epidural analgesia during the stressful period, on cardiac
      events was evaluated in a prospective randomized study in 68 patients with hip
      fractures who either had known coronary artery disease or were at high risk for
      coronary artery disease. On admission to the emergency room, patients were
      assigned to receive a usual care analgesic regimen (intramuscular meperidine,
      control group, n = 34) or continuous epidural infusion of local anesthetic and
      opioid (epidural group, n = 34). Monitoring in the preoperative period included a
      preoperative history and physical examination, daily assessment of cardiac
      adverse events, serial electrocardiograms, cardiac enzymes, and pain scores.
      RESULTS: Preoperative adverse cardiac events were significantly more prevalent in
      the control group compared with the epidural group (7 of 34 0 of 34; = 0.01).
      Adverse cardiac events included fatal myocardial infarction in three, fatal
      congestive heart failure in one, nonfatal congestive heart failure in one, and
      new onset atrial fibrillation in two. The incidence of intraoperative and
      postoperative adverse cardiac events was similar for the two groups. The
      significant difference between groups in the incidence of preoperative cardiac
      events prompted interruption of the study after the planned interim analysis.
      CONCLUSIONS: The authors' data indicate that compared with conventional
      analgesia, early administration of continuous epidural analgesia is associated
      with a lower incidence of preoperative adverse cardiac events in elderly patients
      with hip fracture who have or are at risk for coronary artery disease.
      Preoperative epidural analgesia may be advantageous for this surgical population.

PMID- 12502993
TI  - Comparison of povidone iodine and DuraPrep, an iodophor-in-isopropyl alcohol
      solution, for skin disinfection prior to epidural catheter insertion in
      parturients.
AB  - BACKGROUND: Although rare, infectious sequelae of epidural analgesia can occur. A
      recently marketed antiseptic solution (DuraPrep) which contains an iodophor in
      isopropyl alcohol, may provide enhanced and longer-lasting antimicrobial activity
      and thus be useful in the obstetric setting. The purpose of this study was to
      evaluate the antisepsis achieved with DuraPrep compared with povidone iodine
      (PI). METHODS: Sixty women in active labor who requested epidural analgesia were
      randomly assigned to receive skin preparation with either PI or DuraPrep
      solution. A total of three cultures were obtained from each subject. The first
      was obtained just prior to skin disinfection, the second was obtained immediately
      following antisepsis, and the third was obtained just before removal of the
      catheter. In addition, the distal tip of the catheter was also submitted for
      culture. RESULTS: The clinical characteristics and the risk factors for infection
      were similar in the two groups. The proportion of subjects with positive skin
      cultures immediately after skin disinfection differed significantly between the
      PI and DuraPrep groups (30 3%, respectively, P = 0.01). The number of subjects
      with any positive skin cultures at the time of catheter removal was greater in
      the PI group as compared to the DuraPrep group (97 50%, respectively, P =
      0.0001), as was the number of organisms cultured from skin (log CFU 1.93 +/- 0.40
      0.90 +/- 0.23, respectively, P = 0.03). Six catheters, all from the PI group,
      yielded positive cultures by the roll-plate technique. CONCLUSION: As compared to
      PI, DuraPrep solution was found to provide a greater decrease in the number of
      positive skin cultures immediately after disinfection, as well as in bacterial
      regrowth and colonization of the epidural catheters.

PMID- 12502994
TI  - Transient up-regulation of spinal cyclooxygenase-2 and neuronal nitric oxide
      synthase following surgical inflammation.
AB  - BACKGROUND: Surgery induces pain and hyperalgesia postoperatively. The products
      of cyclooxygenases and nitric oxide synthase (NOS) have been implicated in the
      development of inflammatory pain and hyperalgesia experimentally, and the use of
      drugs clinically that modify cyclooxygenase activity has been advocated in the
      management of perioperative pain. However, regulation of these enzymes following
      surgery has not been studied. METHODS: Adult female sheep (n = 12) undergoing a
      midline laparotomy for collection of ova were used in this study. Lumbar and
      cervical spinal cord tissue was collected from animals euthanized 1 day and 6 or
      7 days after surgery and processed for cyclooxygenase (cyclooxygenase-1 and
      cyclooxygenase-2), neuronal NOS mRNA expression using reverse-transcription
      polymerase chain reaction and hybridization. Tissues were also processed for
      NADPH-diaphorase staining and cyclooxygenase-1 and cyclooxygenase-2 protein
      expression by immunohistochemistry and Western blotting. RESULTS: No alteration
      in cyclooxygenase-1 or cyclooxygenase-2 mRNA or protein concentrations were
      detected in spinal cord by reverse-transcription polymerase chain reaction and
      Western blotting, respectively, at 1 day or 6 or 7 days after surgery. However,
      using techniques that localize mRNA and protein expression ( hybridization and
      immunohistochemistry, respectively), increases in cyclooxygenase-2 were
      identified in lamina V dorsal horn neurons in lumbar spinal cord 1 day after
      surgery. A significant increase in neuronal NOS mRNA was observed in lumbar
      spinal cord 1 day after surgery, localized to laminae I-II and lamina V neurons,
      which returned to baseline concentrations by 6 to 7 days. NADPH-diaphorase
      staining was significantly increased in laminae I-II in lumbar spinal cord 1 day
      after surgery but not after 6 to 7 days. CONCLUSIONS: Spinal cyclooxygenase and
      neuronal NOS pathways are differentially altered following surgical inflammation.
      The early and transient nature of these changes suggests that these enzymes are
      implicated in postoperative pain and hypersensitivity.

PMID- 12502995
TI  - On the mechanism by which epinephrine potentiates lidocaine's peripheral nerve
      block.
AB  - BACKGROUND: Adding epinephrine to lidocaine solutions for peripheral nerve block
      potentiates and prolongs the action, but by incompletely understood mechanisms.
      In an effort to discriminate the pharmacokinetic from the pharmacodynamic effects
      of epinephrine, the authors measured the lidocaine content of peripheral nerve
      over the course of block produced by 0.5% lidocaine, with and without
      epinephrine, and correlated it with the degree of analgesia. METHODS:
      Percutaneous sciatic nerve blocks were performed in 18 groups of rats (10 in
      each) with 0.1 ml of either 0.5% lidocaine or 0.5% lidocaine with epinephrine
      (1:100,000). Over the full course of nerve block, the authors regularly measured
      analgesia to toe pinch and then rapidly removed nerves to assay intraneural
      lidocaine content at 2-120 min after injection. RESULTS: The kinetics of
      lidocaine's clearance from nerve was composed of a fast-decaying transient
      superimposed on a very slowly decaying component. The effect of epinephrine on
      the intraneural lidocaine content was to increase the amount of lidocaine in the
      slow-decaying component by threefold to fourfold, although the total neural
      content was not altered by epinephrine for the first 10 min after injection.
      Epinephrine prolonged blockade by almost fourfold and enhanced the intensity of
      peak analgesia, as well as the fraction of rats with complete block, almost
      throughout the 2-120-min period of behavioral observation. CONCLUSIONS: Adding
      epinephrine to lidocaine solutions increases the intensity and duration of
      sciatic nerve block in the rat. The early increase in intensity is not matched
      with an increase in intraneural lidocaine content at these early times, although
      the prolonged duration of block by epinephrine appears to correspond to an
      enlarged lidocaine content in nerve at later times, as if a very slowly emptying
      "effector compartment" received a larger share of the dose. The increase in early
      analgesia without increased lidocaine content may be explained by a
      pharmacodynamic action of epinephrine that transiently enhances lidocaine's
      potency, but also by a pharmacokinetic effect that alters the distribution of the
      same net content of lidocaine within the nerve.

PMID- 12502996
TI  - Comparison of the visceral antinociceptive effects of spinally administered MPV
      2426 (fadolmidine) and clonidine in the rat.
AB  - BACKGROUND: The authors determined the visceral antinociceptive effect induced by
      MPV-2426 (fadolmidine), a selective alpha 2 -adrenoceptor agonist, in rats with
      and without inflammation of the colon. They also determined whether the
      sympathetic nervous system or intact descending pathways are critical for the
      alpha 2 -adrenoceptor-induced visceral antinociception. METHODS: Spinal neuronal
      responses evoked by colorectal distension were recorded in pentobarbitone
      anesthetized rats. MPV-2426 was administered onto the spinal cord. Clonidine was
      used as a reference alpha 2 -adrenoceptor agonist. Inflammation of the colon was
      induced by turpentine. Sympathectomy was induced by 6-hydroxydopamine. A
      midthoracic transection of the spinal cord was performed to study the role of
      descending pathways. RESULTS: Spinal administration of MPV-2426 produced a dose
      dependent attenuation of responses evoked by colorectal distension, and this
      effect was of the same percentual magnitude in inflamed as in noninflamed
      animals. Clonidine and MPV-2426 induced equipotent visceral antinociception. The
      effect by spinally administered MPV-2426 was enhanced by a chemical sympathectomy
      but not influenced by spinal transection. CONCLUSIONS: Spinally administered MPV
      2426 produces a dose-dependent visceral antinociception as well in animals with
      an inflammation of the colon as in controls. The visceral antinociceptive effect
      induced by spinal MPV-2426 is equipotent to that of spinal clonidine. An intact
      sympathetic nervous system or intact brainstem-spinal pathway is not critical for
      the MPV-2426-induced visceral antinociception.

PMID- 12502997
TI  - Modulation of peripheral endogenous opioid analgesia by central afferent
      blockade.
AB  - BACKGROUND: Peripheral tissue injury causes a migration of opioid peptide
      containing immune cells to the inflamed site. The subsequent release and action
      of these peptides on opioid receptors localized on peripheral sensory nerve
      terminals causes endogenous analgesia. The spinal application of opioid drugs
      blocks the transmission of nociceptive information from peripheral injury. This
      study investigates the influence of exogenous spinal opioid analgesia on
      peripheral endogenous opioid analgesia. METHODS: Six and forty-eight hours after
      initiation of continuous intrathecal morphine infusion and administration of
      Freund's complete adjuvant into the hind paw of rats, antinociceptive and
      antiinflammatory effects were measured by paw pressure threshold, paw volume, and
      paw temperature, respectively. Inflammation and quantity of opioid-containing
      cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim
      stress-induced endogenous analgesia was examined 24 h after discontinuation of
      intrathecal morphine administration. RESULTS: Intrathecal morphine (10 micro g/h)
      resulted in a significant and stable increase of paw pressure threshold ( P<
      0.05) without changing inflammation, as evaluated by paw volume, paw temperature,
      and flow cytometry ( P> 0.05). At 48 but not at 6 h after Freund's complete
      adjuvant, the number of beta-endorphin-containing cells and cold water swim
      induced antinociception were significantly reduced in intrathecal morphine
      treated rats compared with those treated with intrathecal vehicle ( P< 0.05).
      CONCLUSIONS: These findings suggest an interplay of central and peripheral
      mechanisms of pain control. An effective central inhibition of pain apparently
      signals a reduced need for recruitment of opioid-containing immune cells to
      injured sites.

PMID- 12502998
TI  - Intrathecal lidocaine reverses tactile allodynia caused by nerve injuries and
      potentiates the antiallodynic effect of the COX inhibitor ketorolac.
AB  - BACKGROUND: Systemic lidocaine and other local anesthetics reduce
      hypersensitivity states induced by both acute inflammation and peripheral nerve
      injury in animals and produce analgesia in some patients with chronic pain. The
      mechanisms underlying the antiallodynic effect of systemic lidocaine are unclear,
      although most focus is on peripheral mechanisms. Central mechanisms, particularly
      at the spinal dorsal horn level, are less known. In this study, the authors aimed
      to determine whether intrathecal lidocaine has an antiallodynic effect on
      established mechanical allodynia in two well-characterized neuropathic pain rat
      models: partial sciatic nerve ligation (PSNL) and spinal nerve ligation (SNL).
      METHODS: Lidocaine (100-300 micro g) was intrathecally injected in PSNL and SNL
      rats. The withdrawal threshold of both hind paws in response to mechanical
      stimulation was measured using a series of calibrated von Frey filaments.
      RESULTS: This single injection reduced ongoing tactile allodynia in PSNL and SNL
      rats. The antiallodynic effect of intrathecal lidocaine lasted longer in PSNL (>
      3 days) than in SNL rats (< 3 days). Intraperitoneal lidocaine (300 micro g) had
      no effect on tactile allodynia in PSNL rats. In SNL rats, prior intrathecal
      lidocaine (200 and 300 micro g) potentiated the antiallodynic effect of
      intrathecal ketorolac, a nonselective cyclooxygenase inhibitor. Intrathecal
      ketorolac alone had no antiallodynic effect on SNL rats. However, prior
      intrathecal lidocaine (100 micro g) failed to potentiate the antiallodynic effect
      of intrathecal ketorolac. CONCLUSION: The authors' data suggest that intrathecal
      lidocaine possibly suppressed the hyperexcitability of the dorsal horn neurons
      and likely interacted with eicosanoid systems in the spinal dorsal horn.

PMID- 12502999
TI  - Loss of T-type calcium current in sensory neurons of rats with neuropathic pain.
AB  - BACKGROUND: Pathophysiology in the primary sensory neuron may contribute to
      chronic neuropathic pain. Ca channels play a central role in neuronal processes,
      and sensory neurons are rich in low-voltage-activated calcium channels (LVACCs).
      However, the physiologic function of these channels is unknown. Their possible
      role in rebound burst firing makes them a candidate for increased excitability
      after neuropathic injury. METHODS: This study uses pharmacological methods to
      isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham
      operated rats, including the blockade of high-voltage-activated Ca channels with
      fluoride and selective toxins. LVACCs were examined with conventional whole cell
      patch clamp electrophysiology techniques. RESULTS: After chronic constriction
      injury of the peripheral axon, LVACC was significantly reduced compared to sham
      rats as shown by a 60% reduction in peak current density and an 80% reduction in
      total calcium influx. A depolarizing shift in the voltage dependence of
      activation and an increase in the rate of deactivation and inactivation appear to
      cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC,
      applied in the bath to normal dorsal root ganglion cells during current clamp
      significantly and reversibly increased excitability. CONCLUSIONS: These results
      suggest that loss of LVACC may contribute to decreased spike frequency adaptation
      and increased excitability after injury to sensory neurons. Through decreased
      Ca2+ influx, the cell becomes less stable and more likely to initiate or transmit
      bursts of action potentials. Consequently, modulation of Ca2+ currents at the
      dorsal root ganglion may be a potential method of therapeutic intervention.

PMID- 12503000
TI  - Spinal nitric oxide contributes to the analgesic effect of intrathecal [d-pen2,d
      pen5]-enkephalin in normal and diabetic rats.
AB  - BACKGROUND: Spinal nitric oxide (NO) is important for the analgesic actions of
      morphine and cholinergic agents. Its role in the analgesic effect of delta-opioid
      receptor agonists is not known. In the present study, the authors determined the
      role of spinal endogenous NO in the antinociceptive effect of intrathecal [D
      Pen2, D-Pen5 ]-enkephalin (DPDPE), a delta-opioid receptor agonist, in normal
      rats and a rat model of diabetic neuropathic pain. METHODS: Rats were rendered
      diabetic with streptozotocin (50 mg/kg, intraperitoneal). Intrathecal catheters
      were implanted in age-matched normal and diabetic rats. Nociceptive thresholds
      were determined by application of a noxious pressure stimulus to the hind paw.
      The dose-dependent effect of intrathecal DPDPE was first determined. The role of
      spinal NO in the analgesic effect of intrathecal DPDPE was then examined through
      intrathecal treatments with NO synthase inhibitors (NMMA and TRIM) and a specific
      NO scavenger (carboxy-PTIO). RESULTS: The diabetic rats developed a sustained
      mechanical hyperalgesia within 3 weeks after streptozotocin injection.
      Intrathecal DPDPE, 2-20 micro g, dose-dependently increased the withdrawal
      threshold in response to the noxious pressure in normal and diabetic rats.
      However, the ED(50) of DPDPE in diabetic rats was about twofold higher than that
      in normal rats. Intrathecal pretreatment with NMMA, TRIM, or carboxy-PTIO
      diminished the analgesic effect of DPDPE in both normal and diabetic rats.
      Furthermore, the inhibitory effect of NMMA on the action of intrathecal DPDPE was
      reversed by intrathecal l-arginine but not d-arginine. CONCLUSIONS: Intrathecal
      DPDPE produces an antinociceptive effect in normal rats and a rat model of
      diabetic neuropathic pain. Spinal endogenous NO contributes importantly to the
      analgesic action of intrathecal DPDPE in both normal and diabetic neuropathic
      pain conditions.

PMID- 12503001
TI  - Fentanyl decreases Ca2+ currents in a population of capsaicin-responsive sensory
      neurons.
AB  - BACKGROUND: Neuraxial opioids produce analgesia in part by decreasing excitatory
      neurotransmitter release from primary nociceptive neurons, an effect that may be
      due to inhibition of presynaptic voltage-activated Ca2+ channels. The purpose of
      this study was to determine whether opioids decrease Ca2+ currents (I Ca ) in
      primary nociceptive neurons, identified by their response to the algogenic agent
      capsaicin. METHODS: I was recorded from acutely isolated rat dorsal root ganglion
      neurons using the whole cell patch clamp technique before, during, and after
      application of the micro -opioid agonist fentanyl (0.01-1 micro m). Capsaicin was
      applied to each cell at the end of the experiment. RESULTS: Fentanyl reduced I Ca
      in a greater proportion of capsaicin-responsive cells (62 of 106, 58%) than
      capsaicin-unresponsive cells (2 of 15, 13%; P < 0.05). Among capsaicin-responsive
      cells, the decrease in I Ca was 38 +/- 3% (n = 36, 1 micro m) in fentanyl
      sensitive cells just 7 +/- 1% (n = 15, 1 micro m; P < 0.05) in fentanyl
      insensitive cells. Among capsaicin-responsive cells, I Ca inactivated more
      rapidly in fentanyl-sensitive cells (tau, 52 +/- 4 ms, n = 22) than in fentanyl
      insensitive cells (93 +/- 14 ms, n = 24; P < 0.05). This was not due to
      differences in the types of Ca2+ channels expressed as the magnitudes of omega
      conotoxin GVIA-sensitive (N-type), nifedipine-sensitive (L-type), and
      GVIA/nifedipine-resistant (primarily P-/Q-type) components of I Ca were similar.
      CONCLUSIONS: The results show that opioid-sensitive Ca2+ channels are expressed
      by very few capsaicin-unresponsive neurons but by more than half of capsaicin
      responsive neurons. The identity of the remaining capsaicin-responsive (and
      therefore presumed nociceptive) neurons that express opioid-insensitive Ca2+
      channels is unknown but may represent a potential target of future non-opioid
      based therapies for acute pain.

PMID- 12503002
TI  - Estimating times of surgeries with two component procedures: comparison of the
      lognormal and normal models.
AB  - BACKGROUND: Variability inherent in the duration of surgical procedures
      complicates surgical scheduling. Modeling the duration and variability of
      surgeries might improve time estimates. Accurate time estimates are important
      operationally to improve utilization, reduce costs, and identify surgeries that
      might be considered outliers. Surgeries with multiple procedures are difficult to
      model because they are difficult to segment into homogenous groups and because
      they are performed less frequently than single-procedure surgeries. METHODS: The
      authors studied, retrospectively, 10,740 surgeries each with exactly two CPTs and
      46,322 surgical cases with only one CPT from a large teaching hospital to
      determine if the distribution of dual-procedure surgery times fit more closely a
      lognormal or a normal model. The authors tested model goodness of fit to their
      data using Shapiro-Wilk tests, studied factors affecting the variability of time
      estimates, and examined the impact of coding permutations (ordered combinations)
      on modeling. RESULTS: The Shapiro-Wilk tests indicated that the lognormal model
      is statistically superior to the normal model for modeling dual-procedure
      surgeries. Permutations of component codes did not appear to differ significantly
      with respect to total procedure time and surgical time. To improve individual
      models for infrequent dual-procedure surgeries, permutations may be reduced and
      estimates may be based on the longest component procedure and type of anesthesia.
      CONCLUSIONS: The authors recommend use of the lognormal model for estimating
      surgical times for surgeries with two component procedures. Their results help
      legitimize the use of log transforms to normalize surgical procedure times prior
      to hypothesis testing using linear statistical models. Multiple-procedure
      surgeries may be modeled using the longest (statistically most important)
      component procedure and type of anesthesia.

PMID- 12503003
TI  - Perioperative hearing impairment.

PMID- 12503004
TI  - Conscious volunteers developed hypoxemia and pulmonary collapse when breathing
      air and oxygen at reduced lung volume.
AB  - Ventilation at maximal voluntary reduction of lung volume caused significant
      desaturation in some healthy subjects breathing air. Saturation rapidly returned
      to control levels when normal lung volume was regained. These changes are
      probably due to reversible airway obstruction. During the inhalation of oxygen,
      ventilation at maximal voluntary reduction of lung volume caused, in one subject,
      a reduction of arterial Po2 of 243 mmHg. Normal arterial Po2 was not immediately
      restored on regaining normal lung volume. Chest radiographs showed extensive
      atelectasis, which persisted for several hours in an ambulant subject. These
      changes are probably due to absorption of oxygen from alveoli beyond obstructed
      airways. Reduction of lung volume may be harmful for patients who are breathing
      oxygen. Caution is therefore necessary in the use of a subatmospheric pressure
      phase during artificial ventilation and during suction of the tracheobronchial
      tree.

PMID- 12503005
TI  - Late onset of cortical blindness in a patient with severe preeclampsia related to
      retained placental fragments.

PMID- 12503006
TI  - The use of WuScope fiberoptic laryngoscopy for tracheal intubation in complex
      clinical situations.

PMID- 12503007
TI  - Hemodynamic instability and delayed emergence from general anesthesia associated
      with inadvertent intrathecal baclofen overdose.

PMID- 12503008
TI  - Selective lobar bronchial blockade following contralateral pneumonectomy.

PMID- 12503009
TI  - Convulsions and refractory ventricular fibrillation after intrathecal injection
      of a massive dose of tranexamic acid.

PMID- 12503010
TI  - Open chest tension pneumothorax during lung volume reduction surgery via
      sternotomy.

PMID- 12503011
TI  - Repeated or prolonged isoflurane exposure reduces mitochondrial oxidizing
      effects.

PMID- 12503012
TI  - Does pancuronium cause prolonged postoperative intubation in cardiac patients?

PMID- 12503013
TI  - Preemptive analgesia: what do we do now?

PMID- 12503014
TI  - Myocardial ischemic preconditioning decreases postischemic oxygen free radical
      production.

PMID- 12503015
TI  - Bispectral index and mitochondrial myopathies.

PMID- 12503016
TI  - [Isolated traumatic serratus anterior muscle palsy].
AB  - PURPOSE OF THE STUDY: The serratus anterior, innervated by the long thoracic
      nerve, participates in shoulder abduction and elevation, stabilizing the scapula
      on the rib cage. Paralysis of the serratus anterior prohibits shoulder abduction
      and elevation beyond 90 degrees and elevation of the spinal border of the
      scapula. We report our experience with traumatic serratus anterior palsy.
      MATERIAL AND METHODS: Our series included 16 patients with traumatic unique
      injury to the long thoracic nerve. Mean age of the patients at the time of the
      accident was 27.6 years. Seven patients were not operated on due to total or
      partial spontaneous recovery. Scapulothoracic arthrodesis or scapulopexy was
      performed in nine patients. RESULTS: For the non-operated patients, mean
      elevation was 125 degrees at diagnosis and 145 degrees at five years follow-up
      with a Constant score of 85 and muscle force reaching 83% (12 kg shoulder
      abduction) of the healthy side. Outcome was rated very good in 4 patients, and
      good, fair and poor in one each. For the operated patients, elevation was 95
      degrees preoperatively and 104 degrees at last follow-up. At four years follow-up
      mean values were: elevation 104 degrees, Constant score 75, muscle force 72% (9
      kg shoulder abduction) of the healthy side. An infection required a revision
      procedure in one patient who recovered successfully. Outcome was rated very good
      in six patients and good in three. DISCUSSION: Several types of treatment have
      been proposed for serratus anterior palsy: non-operative care, muscle transfers
      mainly with pectoralis major flaps, and scapulothoracic arthrodesis. Most of the
      series on scapulothoracic arthrodesis have concerned fascioscapulohumeral
      dystrophy and cannot be compared with our patients. Data in the literature on
      muscle transfers, which could be considered as comparable with our trauma
      injuries, have demonstrated good results for shoulder motion but a limited effect
      on overall muscle force. In our series, scapulothoracic arthrodesis provided good
      results for muscle force, pain relief, and overall shoulder function, with
      shoulder motion being limited by the position of the arthrodesed scapula. We
      propose this type of treatment for serratus anterior palsy mainly for manual
      laborers.

PMID- 12503017
TI  - [Scoliosis and congenital diaphragmatic agenesis].
AB  - PURPOSE OF THE STUDY: Diaphragmatic agenesis is the most extreme anatomic form of
      congenital diaphragmatic defects. Clinically this pathology is not different from
      posterolateral diaphragmatic hernia described by Bochdalek. We describe our
      observations of scoliosis in 16 neonates with diaphragmatic agenesis. MATERIAL
      AND METHODS: Between 1987 and 1996, 69 neonates underwent surgery for a
      congenital diaphragmatic hernia (CDH) at our institution. Sixteen of these
      patients had the most extreme form of CDH. Ten of these 16 patients survived.
      Spinal and/or chest wall deformities were observed in nine patients, including
      isolated scoliosis in two patients, scoliosis associated with a chest wall
      deformity in three, and isolated chest wall deformity (pectus excavatum or pectus
      carnium) in four. These deformities developed between 13 months and three and a
      half years of age (mean: two years). RESULTS: For two patients the deformity was
      mild (Cobb angle<15 degrees ) and required only observation. A Milwaukee brace
      was used in three patients that had severe kyphoscoliosis. Isolated chest wall
      deformities were treated with observation. No patient required operative
      treatment for these skeletal deformities. DISCUSSION: The preliminary results of
      this study indicate that chest wall deformities and scoliosis frequently occur
      during surgery for diaphragmatic agenesis. Nonoperative treatment is usually
      sufficient, however, follow-up of these patients until adulthood is recommended.

PMID- 12503018
TI  - [Air permeable diaphyseal obturators: efficacity of femoral cementing and
      prevention of associated cardiovascular disorders].
AB  - PURPOSE OF THE STUDY: Insertion of cement plugs into the femoral shaft has become
      an essential part of total hip arthroplasty procedures. The goal is to achieve
      secure cementing of the femoral component, but the pressure induced can cause
      serious problems. The purpose of this study was to determine the effect of a
      flexible bioabsorbable cement restrictor with decompression valves on cementing
      efficacy and to determine the effect of inserting the restrictor then the cement
      plug into the femoral shaft on respiratory functions. MATERIAL AND METHODS: The
      restrictor was implanted in 108 patients undergoing first-intention total hip
      arthroplasty. The canal was prepared and calibrated before inserting the
      restrictor at a depth estimated at preoperative planning to be 10 to 20 mm below
      the tip of the femoral stem. The efficacy of the restrictor was assessed using
      radiographic criteria for the quality of the cement sheath and its position
      relative to the femoral stem. Oxygen saturation of arterial blood and end
      expiration PCO2 were measured at first incision, at insertion of the restrictor,
      at insertion of the cement plug, and at insertion of the femoral stem. RESULTS:
      The relative position of the restrictor was measured on postoperative x-rays at
      less than 20 mm in 75% of the patients, at 20-40 mm in 13% and at more than 40 mm
      in 12%. No cement leakage through the restrictor was identified on postoperative
      x-rays. The quality of the cement sheath was satisfactory in 71% of the patients
      (77 procedures), fair in 20% (22 procedures) and poor in 8% (9 procedures). For a
      first group of patients operated on under spinal anesthesia and optional oxygen
      delivered with a face mask, there was no significant difference in arterial blood
      oxygen saturation before the procedure and during the four explored operative
      times. Conversely, in a second group of patients who had general anesthesia
      without oxygen enrichment of the initial oxygen-nitrogen protoxide gas mixture,
      arterial blood oxygen saturation during the four operative times was
      statistically different from the preoperative value. The same observation was
      made for end-expiratory PCO2. DISCUSSION: The retrictor's decompression valves
      did not allow cement leakage beyond the restrictor. The risk of restrictor
      migration after insertion and after the increased pressure due to cement plug
      insertion was not increased and was found to be less than rates reported in the
      literature. In the patients who had general anesthesia, blood gases showed a
      minimal, but significant, decrease during the operative times susceptible to
      induce increased intramedullary pressure. In patients who had a non-cemented
      acetabular insert, use of the pressure-valve cement restrictor appeared to
      stabilize these parameters.

PMID- 12503019
TI  - [Transfusion of recuperated blood in total knee arthroplasty].
AB  - PURPOSE OF THE STUDY: Autologous blood transfusion is not a routine procedure in
      knee replacement surgery. Several authors have proposed recovering blood shed
      during the procedure to limit the need for homologous transfusions. The purpose
      of this retrospective study was to analyze the amount of blood recovered and
      reinfused with a blood conservation system (MI, USA) and its effect on hemoglobin
      level five days after surgery in 405 consecutive patients undergoing total knee
      arthroplasty. MATERIAL AND METHODS: Preoperative intravascular blood volume and
      hemoglobin level were used to calculate the quantity of hemoglobin transfused
      expressed in g/dl at time t 0 of transfusion then at day 1 and day 5 postop.
      Autologous blood transfusion was not programmed for any of these patients. Twenty
      patients were given homologous blood transfusions and were excluded from the
      analysis of data on recovered shed blood but were included in the analysis of
      risk of homologous transfusion. The analysis thus included 385 patients who did
      not require homologous blood transfusion. Shed blood was reinfused in 337
      patients; no transfusion was performed for 48 patients whose drainage produced an
      insufficient volume. The same analysis was performed for three sub-groups of
      patients: 205 patients whose transfusion volume was less than 10% of their
      intravascular volume, 132 patients whose transfusion volume was greater than 10%
      of their intravascular volume, and 50 transfused patients who weighed less than
      70 kg. RESULTS: Mean transfusion volume was 516 ml (range 100-1440 ml),
      accounting for 59% of the drainage volume over 24 hours and 32% of total
      estimated blood loss. On the average, the whole blood shed and reinfused
      contained 60.60 g hemoglobin and increased serum hemoglobin by 0.97 g/dl at day 5
      postop (with a wide range: 0.18-2.74 g/dl). Mean transfusion volume, based on
      hemoglobin equivalent packed cell units, corresponding to 10% of the mean
      intravascular volume was taken as the threshold of transfusion efficacy. Among
      the 132 patients whose transfusion volume was greater than 10% of the intra
      vascular volume, hemoglobin level at day 5 postop increased 1.32 g/dl on the
      average. Among the 205 patients whose transfusion volume was less than 10% of the
      intravascular volume, hemoglobin level on day 5 postop increased 0.74 g/dl on the
      average. In patients weighing less than 70 kg, transfusion increased hemoglobin
      level on day 5 postop 1.23 g/dl on the average. The probability of transfusion of
      more than 10% of the intravascular volume was 0.66 +/- 0.1 in patients weighing
      less than 70 kg and 0.33 +/- 0.05 for the entire population (p<0.001). The fall
      in mean hemoglobin level from day 0 to day 5 was 3.46 g/dl in transfused patients
      and 4.16 g/dl in non-transfused patients (p<0.0001). Reinfusion of shed blood
      allowed 80 more patients (20% of the 405 patients in this series) to maintain
      their hemoglobin level above 9 g/dl on day 5 postop. The probability of
      homologous blood transfusion for serum hemoglobin<8 g/dl was 0.5 +/- 0.08.
      Applying this probability in a situation without recovery of shed blood, the
      total number of homologous blood transfusions would have increased from 4.9% to
      10.7% (p<0.01). DISCUSSION: Patient follow-up confirmed the absence of specific
      problems. Mean transfusion volume was 516 ml with a 59% (mean)
      reinfusion/drainage ratio, in line with data reported in the literature. The
      efficacy of the blood conservation system was unpredictable due to the wide range
      of blood volume transfused, and consequently of hemoglobin transfused, related to
      wide interindividual variability for total blood loss and drainage volume. Since
      the mean volume of reinfused blood contained the same quantity of hemoglobin as
      one packed red cell units, it would appear reasonable to take 10% of theoretical
      intravascular volume as a threshold above which the transfusion method becomes
      efficacious. CONCLUSION: Considerable interindividual variability in total blood
      loss and total drainage volume compromises the overall efficacy of blood
      conservation systems. Increase in hemoglobin level on day 5 postop was vary
      variable in this series of reinfused knee arthroplasty patients (range 0.18 -
      2.74 g/dl) with a mean of 0.97 g/dl which corresponds to one packed red cell
      unit. The probability that the transfused volume would be greater than 10% of the
      theoretical intravascular volume was 0.66 +/- 0.1 in patients weighing less than
      70 kg versus 0.33 +/- 0.05 for the entire population (p<0.001). This finding
      would suggest that a blood conservation system should be used routinely in
      patients weighing less than 70 kg. Conversely, the use of the system as a routine
      measure for all knee arthroplasty patients with the aim of limiting the risk of
      homologous blood transfusion to a minimum would divide the risk by two and also
      avoid the risk of viral contamination and identification errors.

PMID- 12503020
TI  - [Validation of an experimental protocol of an optoelectronic analysis of
      continuous active knee kinematics in vitro].
AB  - PURPOSE OF THE STUDY: In vitro experiments are particularly useful for studying
      kinematic changes in the normal knee exposed to experimental conditions
      simulating different disease states. We developed an experimental protocol
      allowing a kinematic analysis of the femorotibial and femoropatellar joints in
      healthy knees and after implantation of a knee prosthesis, using a central pivot
      to simulate active loaded movement from the standing to sitting position.
      EXPERIMENTAL SETUP: An experimental device was designed to apply force to the
      femur of a cadaveric specimen including the femur, the patella and the tibia. The
      tibia was angled in the sagittal plane and the femur was free to move in space in
      response to the geometric movement of the knee joint, the capsuloligamentary
      structures, the quadriceps tendon and gravity. Variation in the length of the
      quadriceps tendon controlled the flexion-extension movement. The experimental
      setup included computer-controlled activation allowing continuous coordinated
      movement of the femur relative to the tibia and of the tibia relative to the
      ground. Standard activations simulated movement from the standing to the sitting
      position. STUDY PROTOCOL: Five pairs of fresh-frozen cadaver specimens including
      the entire femur, patella, tibia and fibula, the capsuloligamentary and intra
      articular structures of the knee, the superior and inferior tibiofibular
      ligaments and the quadriceps tendon were studied. The quadriceps tendon was
      connected to the computer-guided activation device. Reflectors were fixed onto
      the anterior aspect of the femur, the superior tibial epiphysis and the center of
      the patella. Anatomic landmarks on the femur, the tibia, and the patella were
      identified to determine the plane of movement of each bone in the three rotation
      axes and the three translation directions. Three infrared cameras recorded
      movements of the reflectors fixed on the bony segments and, by mathematical
      transformation, the movement of the corresponding bony segment, displayed in time
      course curves. RESULTS: The precision of the measurements, evaluated in a
      previous study, was +/- 1.5 degrees for rotation and +/- 0.5 mm for translation
      movements. Three acquisitions were made for each experiment and produced results
      differing less than one degree. A qualitative analysis of femorotibial and
      femoropatellar kinematics was achieved for the normal knee. The automatic
      internal rotation of the femur during flexion was observed and the patellar
      kinematics were defined with six degrees of freedom. DISCUSSION: This
      experimental setup enables a comparison of the kinetics of a normal knee with the
      kinetics observed after implantation of a prosthesis on the same knee. The
      kinetic analysis does not involve a succession of static states but rather a
      continuous movement generated by the action of the quadriceps that can be loaded,
      simulating partial weight bearing. Using the markers fixed directly on the bones,
      this in vitro study allowed remarkably precise and reproducible measurements. The
      movements simulated regularly encountered clinical situations. The quality of the
      movement recorded for a given prosthesis thus provides an accurate approach to
      the quality of the prosthesis. The goal is not to define the exact kinematics of
      the normal knee but rather to compare the kinematics of the normal knee with that
      of the same knee after prosthesis implantation allowing an accurate method for
      assessing prosthesis design and studying the influence of different parameters,
      particularly the ligaments. Concomitant study of femorotibial and femoropatellar
      kinematics provides further information rarely found in the literature.

PMID- 12503021
TI  - [In vitro analysis of the continuous active patellofemoral kinematics of the
      normal and prosthetic knee].
AB  - PURPOSE OF THE STUDY: In vitro experiments are particularly useful for studying
      kinematic changes from the normal knee to experimental conditions simulating
      different disease states. We developed an experimental protocol allowing a
      kinematic analysis of the femorotibial and femoropatellar joints in the healthy
      knee and after implantation of a knee prosthesis, according to the central pivot
      during simulated active loaded movement from the standing to sitting position.
      EXPERIMENTAL SETUP: An experimental device was designed to apply force to the
      femur of a cadaveric specimen including the femur, the patella and the tibia. The
      tibia was angled in the sagittal plane and the femur was free to move in space in
      response to the geometric movement of the knee joint, the capsuloligamentary
      structures, the quadriceps tendon and gravity. Variation in the length of the
      quadriceps tendon controlled the flexion-extension movement. The experimental
      setup included computer-controlled activation allowing continuous coordinated
      movement of the femur relative to the tibia and of the tibia relative to the
      ground. Standard activations simulated movement from the standing to the sitting
      position. STUDY PROTOCOL: Five pairs of fresh-frozen cadaver specimens including
      the entire femur, patella, tibia and fibula, the capsuloligamentary and intra
      articular structures of the knee, the superior and inferior tibiofibular
      ligaments and the quadriceps tendon were studied. The quadriceps tendon was
      connected to the computer-guided activation device. Reflectors were fixed onto
      the anterior aspect of the femur, the superior tibial epiphysis and the center of
      the patella. Anatomic landmarks on the femur, the tibia, and the patella were
      identified to determine the plane of movement of each bone in the three rotation
      axes and the three translation directions. Three infrared cameras recorded
      movements of the reflectors fixed on the bony segments and, by mathematical
      transformation, the movement of the corresponding bony segment, displayed in time
      course curves. RESULTS: The patella moved in continuous fashion over the femur,
      directly following the angle of knee flexion with a ratio of about 60%, which was
      constant for all knees studied and for all configurations. The patella of healthy
      knees and knees implanted with a unicompartmental prosthesis exhibited medial
      rotation during the first 30 degrees of flexion, with a movement of about of 10
      degrees, then a lateral rotation of about 10 degrees to 20 degrees when the
      flexion reached 90 degrees; implantation of a total knee prosthesis led to a
      medial rotation which was continuous from 5 degrees to 15 degrees. There was a
      trend towards continuous abduction of about 10 degrees. The patella exhibited a
      continuous anterior translation of 10 to 20 mm from the tibia with increasing
      knee flexion, in both normal and prosthetic knees (unicompartmental prosthesis);
      knees implanted with a total knee prosthesis exhibited 5 to 10 mm anterior
      translation from 0 degrees to 50 degrees flexion, then an equivalent posterior
      translation for 50 degrees to 90 degrees flexion. The patella made a continuous 5
      to 10 mm medial translation movement over the tibia in both normal and prosthetic
      (unicompartmental) knees; knees implanted with a total knee prosthesis exhibited
      0 to 5 mm lateral translation starting after 50 degrees flexion. The patella also
      exhibited a continuous distal translation over the tibia of about 20 to 30 mm,
      for all configurations. DISCUSSION: The experimental set up enables a comparison
      of the kinetics of a normal knee with the kinetics observed after implantation of
      a prosthesis on the same knee. Implantation of a unicompartmental medial
      prosthesis, leaving the posterior cruciate ligament intact and irrespective of
      the status of the anterior cruciate ligament, did not, in these experimental
      conditions, exhibit any significant difference in the femorotibial or
      femoropatellar kinetics compared with the same normal knee. Implantation of a
      total knee prosthesis had a significant effect on the femoropatellar kinematics,
      compared with the same knee before implantation. The main anomalies were related
      to the medial-lateral rotation of the patella which exhibited an abnormal lateral
      rotation, possibly favorable for subluxation; these changes were directly related
      to femorotibial rotation after implantation of the total prosthesis and appeared
      to be related to the symmetry of the femoral condyles of the prosthesis model
      studied, perturbing the normal automatic rotation of the knee. There is thus a
      strong relationship between femorotibial and femoropatellar kinetics in the total
      knee prosthesis.

PMID- 12503022
TI  - [Influence of the height of the joint space on the three-dimensional kinetics of
      total knee prostheses and behavior of the lateral ligaments: an in vitro study].
AB  - PURPOSE OF THE STUDY: The level of the joint space can be modified after
      implantation of a total knee prosthesis. Likewise, ligament balance is a cardinal
      point of the surgical technique. The purpose of this in vitro work was to study
      the influence of the position of the distal tibiofemoral joint space after
      implantation of a total knee prosthesis on the three-dimensional kinetics of the
      knee joint and on the behavior of the lateral ligaments. MATERIAL AND METHOD:
      Total knee arthroplasty (TKA) with a posterior stabilized prosthesis was
      performed on seven fresh-frozen cadaver specimens. A specially-designed
      experimental device was used to achieve continuous knee motion simulating hip
      flexion from a vertical position. The Vicon optoelectronic system was used to
      record the femorotibial and femoropatellar kinematics in three dimensions. Two
      electronic goniometers were positioned on the insertions of the lateral ligaments
      to measure ligament displacements during knee movements. Five configurations were
      recorded on each knee: healthy knee, same knee after TKA, and 2-mm and 4-mm
      upward displacement of the prosthetic distal tibiofemoral joint space. Ligament
      balance at extension was preserved in all configurations. The kinematic curves
      obtained were compared with the coefficient of multiple correlation. RESULTS:
      Changing the position of the joint space had a significant effect on the
      kinematics of the patella (rotation and abduction-rotation) but did not have a
      significant effect on the femorotibial kinematics. Variations in the length of
      the lateral ligaments were of small amplitude. Lowering the joint space led to
      laxity at flexion. Raising the joint space tightened the ligaments at flexion.
      DISCUSSION: These results confirm our clinical impression when the level of the
      distal femur cut is set to achieve tension on the ligaments at knee extension. If
      the joint space is lowered, i.e. with a more sparing distal femur cut, the
      prosthesis takes up less space during flexion, leading to laxity at flexion. If
      the joint space is raised, i.e. with an excessive distal femur cut, the
      prosthesis takes up more space during flexion, tightening the lateral ligaments.
      CONCLUSION: The position of the joint space must be rigorously reproduced during
      TKA not only to maintain correct femorotibial kinematics, but most importantly to
      preserve patellar kinematics and proper behavior of the lateral ligaments.
      Ideally, the height of the joint space should be restored first, followed by
      control of the ligament balance. An over- or undercut of the femur can lead to
      defective femoropatellar kinematics and ligament tension at flexion despite good
      ligament balance at extension. In addition, ligament balance should not be
      achieved by displacing the tibial cut or by modifying the thickness of the tibial
      component, which would have an effect not only at extension but also at flexion.

PMID- 12503023
TI  - [Rotational osteotomy technique for congenital radio-ulnar synostosis with
      central medullary nailing and external fixation].
AB  - PURPOSE OF THE STUDY: Congenital radio-ulnar synostosis is a very uncommon
      condition. The functional impairment resulting from the complete pronation
      posture justifies rotational osteotomy. We present a series of six rotational
      osteotomies using the Hernigou-Goutallier technique. MATERIAL AND METHODS: The
      Hernigou-Goutallier osteosynthesis procedure is based on a centromedullary nail
      and two external fixation pins positioned in the ulna at an angle corresponding
      to the desired rotation. The nail is partially withdrawn to allow subperiosteal
      osteotomy in the synostosis via a horizontal incision between the two pins. After
      rotation, the osteotomy is stabilized with clamps holding the external fixation
      pins in parallel. RESULTS: Bone healing was achieved at two months in all six
      cases with no loss of correction. DISCUSSION: Among the different treatments
      proposed for radio-ulnar synostosis, the risk of vessel or nerve injury is high
      with screw-plate fixation despite shortening osteotomy. Palm-tree osteotomy
      raises the same risks and is more invasive and difficult to achieve. The
      rotational osteotomy technique presented here has the advantage of allowing local
      care more easily than with cast fixation. Another important advantage is that an
      overcorrection leading to vessel or nerve injury can be reversed without losing
      the axis, allowing progressive correction if necessary.

PMID- 12503024
TI  - [Stress fracture of the femur: a rare complication of sickle cell disease].
AB  - A 24-year-old patient with homozygous sickle cell disease developed a stress
      fracture of the femur. Successive x-rays demonstrated defective ossification and
      a spontaneous unicortical fracture with no notion of trauma or stressful
      activities (e.g. sports) followed six months later by a bicortical fracture with
      displacement and periosteal reaction leading to the diagnosis of stress fracture.
      This type of fracture has not been reported previously in sickle cell disease.
      The patient was treated with centromedullary nailing. The follow-up was
      uneventful. Bone healing was achieved at three months. The patient was pain free
      and could walk without crutches. Stress fracture is a potential diagnosis in
      homozygous sickle cell disease patients with defective ossification who present
      spontaneous pain even when plain x-rays do not visualize an overt fracture.
      Computed tomography or magnetic resonance imaging should be performed when
      available. Conventional treatment with nailing provides successful cure with good
      functional outcome.

PMID- 12503025
TI  - [Centro-somatic staged tuberculous vertebral osteitis: a case report].
AB  - Centro-somatic tuberculous vertebral osteitis is defined as tuberculous infection
      of the vertebral body with preserved integrity of the adjacent intervertabral
      disk. Other types of vertebral tuberculosis include Pott's spondylodiscitis and
      exceptional lesions of the posterior arch. We report a case of centro-somatic
      tuberculous vertebral osteitis in a 14-year-old boy who developed staged lesions
      of the L2 to S1 bodies, associated with a posterior epidural collection but
      without any deterioration of the intervertebral disk on plain x-rays and computed
      tomography. This atypical aspect of the lesions required a surgical biopsy which
      yielded a yellow-whitish fibro-oleagenous, friable product more suggestive of
      neoplasm than infection, but histology rectified the diagnosis, showing typical
      caseo-follicular tuberculosis. A 6-month anti-tuberculosis regimen was rapidly
      followed by symptom improvement. We emphasize the importance of modern imaging
      techniques for the diagnosis of vertebral lesions and for guided biopsy or
      drainage.

PMID- 12503026
TI  - The influence of sex hormones on circulating nitric oxide (NOx) levels in rhesus
      monkeys (Macaca Mulatta).
AB  - BACKGROUND: The effects of long-term estrogen (E2) replacement therapy (ERT) on
      circulating and bone marrow total plasma nitric oxide (NOx) levels were
      determined in rhesus monkeys. In addition changes in circulating NOx during the
      menstrual cycle were measured. MATERIAL/METHODS: We measured NOx levels in 20
      ovariectomized animals and 27 cycling animals. In the first group monkeys were
      ovariectomized (OVX; n=10) and treated with estrogen implants for 21 months. The
      control group (n=10) was OVX and received vehicle implants only. After 21 months
      systemic NOx status was measured. In a second group of cycling animals NOx was
      measured during the follicular and luteal phases, and correlated with body
      composition parameters determined by dual energy X-ray absorptiometry (DXA)
      analysis. CONCLUSIONS: Replacement of estrogen in OVX monkeys resulted in reduced
      circulating but not bone marrow plasma NOx compared to OVX monkeys. Circulating
      NOx levels in these animals correlated negatively (r(2)= -0.35; P=0.03) with
      estradiol levels. In cycling monkeys luteal levels of NOx were found to be
      significantly higher than follicular levels and correlated negatively (r(2) = 
      0.4; P=0.036) with estradiol but not progesterone levels. Negative correlations
      between NOx levels and body weight, fat and lean mass were also found. RESULTS:
      Long-term ERT influences systemic NOx levels in a negative fashion without
      effects on bone marrow plasma NOx. Circulating NOx was higher during the luteal
      phase. In both ERT treated and cycling monkeys estradiol correlated negatively
      with NOx suggesting the existence of a negative feedback of NO on either NOS
      activity or expression.

PMID- 12503027
TI  - Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse
      and rabbit.
AB  - BACKGROUND: Paracetamol is a potent analgesic and antipyretic drug, but has only
      weak anti-inflammatory activity. Unlike aspirin-like drugs, paracetamol does not
      damage the stomach mucosa or inhibit the aggregation of platelets. The analgesic
      action of paracetamol is on the central nervous system. In vitro, paracetamol
      inhibits cyclooxygenase (COX)-1 and -2 in high concentrations but stimulates in
      low doses. This study examines the stimulation and inhibition of COX-1 and COX-2
      in homogenates of mouse and rabbit tissues and in J774.2 cultured mouse
      macrophages. MATERIAL/METHODS: Mouse and rabbit tissues were removed, homogenised
      and treated with different concentrations of paracetamol. Prostaglandins (PGs) E2
      and I2 were measured in the homogenates to assess the activity of COX-1. Ex vivo
      synthesis of PGE2 was measured in tissues after treating rabbits with 100 mg/kg
      paracetamol. J774.2 cultured mouse macrophages treated with bacterial
      lipopolysaccharide (LPS) to induce COX-2, were treated with varying
      concentrations of paracetamol and the PGs produced were measured. RESULTS: Low
      doses of paracetamol stimulated PG production in J774.2 macrophages and stomach
      mucosa homogenates, but reduced PG production at high concentrations of
      paracetamol. This stimulation did not occur when co-factors were added. The order
      of potency of paracetamol on COX-1 or COX-2 in tissue homogenates was as follows:
      lungs>spleen>brain>J774.2 cells>stomach mucosa. Paracetamol, 100 mg/kg, inhibited
      COX-1 in stomach mucosa ex vivo much less effectively than in other tissues.
      CONCLUSIONS: These data support the hypothesis that paracetamol selectively
      inhibits a COX enzyme which is different from COX-1 or COX-2 and may be a variant
      of COX-1.

PMID- 12503028
TI  - Characterization of dendritic cells generated in vivo by an E. coli derived
      chimeric dual receptor agonist.
AB  - BACKGROUND: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth
      factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross
      species activity and treatment of mice with ProGP-4 results in increases in the
      number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood.
      Herein, we report morphologic, phenotypic and functional evaluation of Class
      II+/CD11c+ cells generated by in vivo administration of ProGP-4.
      MATERIAL/METHODS: C57BL/6 mice were injected daily with ProGP for 7 to 18 days.
      Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to
      enumerate and characterize changes in DC populations. Spleens from ProGP treated
      mice were evaluated by immunocytochemistry and enriched CD11c+ populations were
      functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL
      assay. RESULTS: Administration of this dual receptor agonist to mice resulted in
      dose-dependent increases in the numbers of total white blood cells and Class
      II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4
      treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit
      at lower levels as compared to Class II+/CD11c+ cells from untreated animals.
      Despite lower co-stimulatory molecule expression, ProGP-4-generated Class
      II+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen
      specific T cell hybridoma as efficiently as bone marrow derived dendritic cells
      from untreated mice. CONCLUSIONS: The data presented in this report highlight the
      ability of E. coli derived ProGP-4 to expand large numbers of functional DC in
      the peripheral blood and lymphoid organs in vivo using a rodent model of
      hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may
      enable further investigations of immunotherapeutic approaches to the treatment of
      diseases such as cancer and autoimmunity.

PMID- 12503029
TI  - Critical evaluation of radiolabeled lymphocytes to detect acute renal transplant
      rejection in a large animal model.
AB  - BACKGROUND: Renal transplant rejection cannot be diagnosed with certainty by non
      invasive techniques. These techniques lack the specificity to differentiate
      rejection from other causes of renal dysfunction such as ATN and calcineuria
      toxicity. Since rejection involves lymphocytes, which the other courses of
      dysfunction do not, radiolabeling lymphocytes is an attractive technique to
      diagnose rejection non-invasively. MATERIAL/METHODS: We report our experience
      with this technique in a pig model of renal transplantation. We studied two
      groups of pigs, one with renal autografts and the other with allografts. We
      optimized radiolabeling of lymphocytes and also the technology for detection of
      these lymphocytes. The uptake of the radiolabeled lymphocyte was compared between
      the two groups by surface detection and, at the end of the experiment, with
      scintigraphy of renal tissues. RESULTS: Despite adequate labeling and viability
      of lymphocytes, only 1-2% of injected lymphocytes 'homed' to the renal grafts.
      Furthermore, although the detection technology was optimized, a poor signal to
      noise ratio interfered with the detection of the labeled lymphocytes. Due to
      these problems rejection could not be differentiated from ATN in this model.
      CONCLUSIONS: We conclude that increasing the specific activity of the lymphocytes
      and improving the signal to noise ratio will enhance the specificity and
      sensitivity of this technique and facilitate non-invasive diagnosis of rejection.

PMID- 12503030
TI  - Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes
      synergistic inhibition of growth in HER2-overexpressing breast cancer cells.
AB  - BACKGROUND: The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin)
      is useful in the treatment of ErbB2-overexpressing breast cancers, but its
      efficiency is limited because development of resistance is common. In order to
      study the possibility of improving the efficacy of therapies directed against
      HER2/erbB2, we investigated the effects of co-targeting this receptor and the
      insulin-like growth factor 1 receptor (IGF-1R), a widely-expressed protein
      tyrosine kinase with important roles in suppression of apoptosis and stimulation
      of proliferation. MATERIAL/METHODS: The experimental strategy involved combining
      trastuzumab treatment and reduction of IGF-1R signaling through incremental heat
      induced expression of the dominant-negative IGF-1 receptor 486/STOP under the
      control of the heat-sensitive Drosophila HSP70 promoter, in HER2/erbB2
      overexpressing MCF7her18 breast cancer cells. RESULTS: Isobologram analysis of
      combinatorial treatment data revealed a strong synergistic interaction between
      trastuzumab treatment and the induction of the dominant-negative IGF-1R
      expression, resulting in potentiation of growth inhibition in transfected cancer
      cells. CONCLUSIONS: These observations support the concept that simultaneously co
      targeting tyrosine kinase receptors may be therapeutically useful, and provide a
      specific rationale for combining IGF-1R and HER2/erbB2 targeting strategies in
      anti-neoplastic approaches.

PMID- 12503031
TI  - Melatonin effects on megakaryocyte membrane patch-clamp outward K+ current.
AB  - BACKGROUND: This study was carried out to evaluate the influence of melatonin
      concentration on rat bone marrow megakaryocyte outward K+ current and its
      implications with regard to platelet production. It is the Authors' view that the
      greatly extended development of megakaryocyte membrane, together with its ion
      channels, makes the choice of this topic particularly pertinent.
      MATERIAL/METHODS: Megakaryocytes from fresh Wistar rat bone marrow were clampaged
      with patch-clamp technique and the examination of membrane outward current was
      performed when melatonin dissolved in external or internal standard solution was
      used. RESULTS: On the basis of this study, melatonin does reduce outward K+
      current intensity, the more the higher the melatonin concentration. In
      quantitative terms, whereas no change is noticed when dissolved melatonin
      concentration in external standard solution is smaller than 25 mM, at 50 mM only
      a delayed outward current decrease appears. The effect on the outward current
      intensity is reversible at least until melatonin concentration reaches 500 mM;
      when melatonin concentration is higher than 1000 mM the effect is demonstrably
      irreversible. The presence on the megakaryocyte membrane of internal standard
      melatonin solution does reduce the outward current even more sharply.
      CONCLUSIONS: There seems to be a positive correlation between cationic pump and
      megakaryocyte intimate processes of platelet production.

PMID- 12503032
TI  - Agonists of peroxisome-proliferator activated receptor-alpha (clofibrate and
      WY14643) reduce renal ischemia/reperfusion injury in the rat.
AB  - BACKGROUND: The aim of this study was to investigate the effects of peroxisome
      proliferator activated receptor-alpha (PPAR-alpha) agonists, clofibrate and
      WY14643 on the renal dysfunction and injury caused by bilateral
      ischemia/reperfusion (I/R) of rat kidneys in vivo. MATERIAL/METHODS: Male Wistar
      rats were anesthetized with sodium thiopentone (120 mg/kg i.v.) and subjected to
      bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and
      urinary biochemical indicators of renal dysfunction and injury were measured;
      serum creatinine (sCr, glomerular dysfunction), fractional excretion of Na+
      (FENa, tubular dysfunction), and urinary N-acetyl-b-D-glucosaminidase (uNAG,
      tubular injury). Additionally, renal sections were used for histological grading
      of renal injury and for RT-PCR analysis of the expression of PPAR-isoforms in
      kidneys obtained from rats prior to or after I/R. In addition, expression of
      intercellular adhesion molecule-1 (ICAM-1) was determined using Northern blot
      analysis. RESULTS: Using RT-PCR, we document here the expression of PPAR-alpha,
      PPAR-beta and PPAR-gamma1 (but not PPAR-gamma2) in the kidney of the rat. I/R
      resulted in the down-regulation of PPAR-alpha without modulation of any other
      PPAR. Clofibrate and WY14643 significantly reduced the increases in sCr, FENa and
      uNAG caused by renal I/R, indicating attenuation of renal dysfunction and injury.
      Expression of ICAM-1 caused by I/R of the kidney was not modulated by PPAR-alpha
      agonists. CONCLUSIONS: We show here that (i) renal I/R results in the down
      regulation of PPAR-alpha in the kidney, and (ii) that the PPAR-alpha agonists
      clofibrate and WY14643 reduce the renal dysfunction and injury associated with
      I/R of the kidney.

PMID- 12503033
TI  - Activity of cysteine proteases and their inhibitors in the lymph nodes of larynx
      cancer patients.
AB  - BACKGROUND: Cysteine endopeptidases and their inhibitors play an important role
      in the process of carcinogenesis. Positive correlation has been found between
      tumor invasiveness, its metastatic potential and the secretion of cysteine
      endopeptidases. Cysteine protease inhibitory activity is also altered in
      malignant tumors and various body fluids of patients with cancer.
      MATERIAL/METHODS: Total cysteine endopeptidase activity and cysteine proteinase
      inhibitory activity were measured in homogenates of cervical lymph node tissue
      surgically obtained from the larynx of cancer patients. The tissue samples were
      histologically examined, and each was divided into two parts: positive (PCN),
      with mostly cancer cells, and negative (NCN), with no cancer cells. RESULTS: In
      the PCNs, the levels of the assayed enzymes and their inhibitors were
      significantly higher than in the NCNs. The mean values of cysteine protease
      activity were 2.70I2.29 and 1.59I1.28 for PCNs and NCNs, respectively (p<0.005).
      The mean values of cysteine protease inhibitors were 9.1I8.6 and 6.1I6.3 for PCNs
      and NCNs, respectively (p<0.02). An altered protease-inhibitor activity ratio was
      also found in PCN samples compared to NCNs. CONCLUSIONS: These data suggest
      increased activity of cysteine peptidases and their inhibitors in the case of
      secondary tumor tissue. The cancer cells metastasized to lymph node tissue
      produce some alteration in balance between cysteine protease activity and the
      endogenous inhibitors of the proteases.

PMID- 12503034
TI  - Relationship of blood pressure measures with coronary artery calcification.
AB  - BACKGROUND: Increased blood pressure level is a major risk factor for coronary
      artery disease. Previous studies of relationships of blood pressure level and
      hypertension status with coronary artery calcification (CAC), a measure of
      subclinical atherosclerosis, were restricted to participants who were physician-
      or self-referred, high risk, selected on hypertension status, or young adults.
      MATERIAL/METHODS: 803 asymptomatic individuals at least age 40 years were studied
      from a community. Blood pressure level was measured and blood pressure diagnostic
      category (i.e. hypertension vs. normotension) was determined by considering
      reported history of physician-diagnosed hypertension, use of antihypertensive
      medication, and measured blood pressure levels. CAC was measured non-invasively
      with electron beam computed tomography. Tobit regression models allowed
      simultaneous modeling of presence and quantity of CAC. RESULTS: In men, age,
      having ever smoked, having hypertension, LDL-C level, and body mass index were
      significantly and positively associated with presence and quantity of CAC. In
      women, age, systolic blood pressure level, use of lipid lowering medications, and
      waist-to-hip ratio were significantly and positively associated with presence and
      quantity of CAC. Relationships of measures of blood pressure with CAC were
      modified by age, but no other risk factors, in both sexes. CONCLUSIONS: Our
      results indicated that measures of blood pressure make a relatively large
      contribution to predictions of CAC at younger ages. CAC quantification,
      especially among younger individuals, may allow for early assessment of the
      presence and extent of target organ disease.

PMID- 12503035
TI  - Role of surgery in pulmonary tuberculosis.
AB  - BACKGROUND: The purpose of our study was to analyze current indications for
      surgery in tuberculosis (TB). We present our experience with TB patients
      presenting with indications for surgery between 1990 and 1998. MATERIAL/METHODS:
      The indications for surgical intervention included 25 cases of pulmonary
      aspergilloma, 19 cases of pneumothorax, 16 cases of pulmonary nodes and masses
      without histological diagnosis, 15 cases of bronchiectasis, 12 cases of massive
      hemoptysis, 12 cases of pleural empyema, and 33 cases of other complications. No
      patients with multidrug-resistant tuberculosis required surgical intervention,
      although 56 were treated during this period. RESULTS: The techniques utilized
      included lobectomy in 45 cases, pleural drainage in 32 cases, segmented pulmonary
      resection in 32 cases, surgical procedures on the thoracic wall in 17 cases,
      pneumonectomy in 10 cases, pleuropulmonary decortication in 8 cases,
      mediastinoscopy in 6 cases, and thoracoscopy in 5 cases. In 25 cases two or more
      procedures were performed on the same patient. In 36 cases (27.3%) there were
      complications, of which persistent air leakage after pulmonary resection was the
      most frequent (n=10). There was a mortality rate of 5.3% (7 CONCLUSIONS: In our
      experience, surgery in the treatment of TB is indicated to resolve sequelae or
      complications, since cases of simple or multidrug-resistant TB can be managed
      pharmacologically. The morbidity and mortality rates in our series were
      acceptable.

PMID- 12503036
TI  - Clinical outcomes and costs of Amplatzer transcatheter closure as compared with
      surgical closure of ostium secundum atrial septal defects.
AB  - BACKGROUND: Transcatheter implantation of the Amplatzer septal occluder (ASO) is
      an alternative to conventional surgical closure of isolated secundum atrial
      septal defects (ASDs). Neither the clinical outcomes nor the costs of these
      procedures have been extensively compared. MATERIAL/METHODS: We performed a
      retrospective cohort study to evaluate cost-effectiveness in patients with
      secundum ASDs who underwent closure using either placement of an ASO or surgery.
      We utilized available TSI accounting data to estimate hospital costs. RESULTS: On
      the basis of trans-thoracic echocardiography, the procedures resulted in
      successful closure of the ASDs in 95.8% of patients in whom the ASO was implanted
      and 96.8% of surgical patients. Although there were no deaths in either group,
      complications occurred in 10.4% of patients in whom the ASO was implanted and
      31.2% of surgical patients. The mean estimated cost per case treated with the ASO
      was $11,541 as compared with $21,780 for surgery. The average length of hospital
      stay per case treated with the ASO was 1.0 day as compared with 4.3 days for
      surgery. Sensitivity analyses based on our data identified no plausible
      situations in which the costs of surgery and of implantation of the ASO would be
      equal. CONCLUSIONS: The equally effective and less costly Amplatzer Septal
      Occluder appears superior to surgical closure of isolated secundum ASDs in
      qualifying patients. The transcatheter method is also associated with
      significantly lower morbidity. Consequently, our results support the use of the
      ASO as an alternative to surgery for the management of this common congenital
      lesion.

PMID- 12503037
TI  - An analysis of prognostic factors and the five-year survival rate in childhood
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in
      childhood. With newer drug protocols the five-year survival rate is now close to
      80%. Various factors have been reported to be important for prognosis and should
      be considered when planning MATERIAL/METHODS: In a cross-sectional study,
      prognostic variables and the five-year survival rate were analyzed. Data
      regarding demographic characteristics, family and personal history,
      manifestations at the time of presentation, therapeutic regimens and outcome were
      collected from the records of 76 ALL patients in treatment five years prior to
      the study. Two pathologists performed the staging using the morphology method
      (L1, L2 and L3). RESULTS: Fifty-five subjects (72.5%) survived until the end of
      the study. One subject succumbed to the rapid fatal course of the disease and 20
      others passed away due to relapses or infection during follow-up. CONCLUSIONS:
      Among all variables a worse prognosis was associated (p<0.05) with WBC counts
      greater than 50,000/ml at presentation, relapse in the CNS, and relapse in the
      bone marrow. When Anthracycline was included in the therapeutic regimen, the
      effect of chemotherapy was more favorable compared to regimens without
      Anthracycline (p<0.05). Other variables previously reported to have prognostic
      value, especially age and sex, were not significant in our study (p>0.05). Other
      factors which might account for a poorer prognosis included the preponderance of
      L-2 morphology, difficult access to medical care, decreased compliance of
      families due to exhausted economic and psychological reserves, and inadequate
      knowledge about the disease course and treatment.

PMID- 12503038
TI  - Prevalence of hepatitis B and C seromarkers and abnormal liver function tests
      among hemophiliacs in Guilan (northern province of Iran).
AB  - BACKGROUND: The aim of this study was to determine the seroprevalence of
      hepatitis B and C viruses and abnormal liver function tests among hemophiliacs in
      Guilan province, Iran. MATERIAL/METHODS: Patients registered with Guilan
      Hemophilia Society (GHS) were enrolled in this study, and evaluated for the
      presence of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV
      Ab) and liver function tests. RESULTS: One hundred and one patients (100 males, 1
      female, mean age 19.7 years, range 3-71 years) from 110 registered hemophiliacs
      were enrolled in this study. 29 patients (28.7%) had elevated Alanine
      aminotransferase (ALT), 27 (26.7%) and 72 (71.3%) were positive for HBsAg and HCV
      Ab, respectively. Seropositivity for HCV-Ab correlated with the duration of
      treatment with clotting factor until 1997 (P=0.01). There was also an inverse
      correlation between factor VIII & IX activity and seropositivity for HCV-Ab
      (P<0.001) and HBsAg (P<0.04). HCV-Ab was more likely to be positive among those
      received lyophilized factor VIII and cryoprecipitate than lyophilized factor VIII
      alone (P<0.01). In addition HCV-Ab seropositivity was more common among those
      received factor IX concentrate and fresh frozen plasma (FFP) than those received
      only FFP (P<0.01). CONCLUSIONS: Based upon our finding, prevalence of HBsAg
      positive cases in Guilan province was higher than other studies. Although
      frequency of HCV-Ab was similar to other studies, frequency of increased ALT was
      less. Upon the results emerged from this study, we recommend that all
      hemophiliacs should be vaccinated against HBV and should have regular program for
      checking HCV.

PMID- 12503039
TI  - Experience with cerebral perfusion in total aortic arch replacement.
AB  - BACKGROUND: The interruption of cerebral circulation is a major problem in the
      surgical repair of the aortic arch. This study was undertaken to identify the
      perioperative risk factors for mortality and neurological morbidity, and the
      outcome after total aortic arch replacement. MATERIAL/METHODS: Between June 1995
      and March 2002, 23 patients (13 males) underwent total aortic arch replacement.
      The mean age was 61.7I9.4 years (range 35-77). All patients underwent total arch
      replacement with a period of hypothermic circulatory arrest (HCA). Selective
      cerebral perfusion was utilized as an adjunct to HCA (retrograde in 19 patients
      and antegrade in 4 patients). The elephant trunk technique was used in 18
      patients, while proximal and middle portion of the descending aorta was also
      replaced in 5 patients. The patient information in our database was
      retrospectively reviewed. The risk factors affecting mortality and morbidity were
      analyzed by univariate analysis. RESULTS: The in-hospital mortality rate was
      17.4%. None of the survivors developed major stroke. Temporary neurological
      dysfunction (TND) was seen in 5 patients. Univariate analysis revealed that
      excessive blood transfusion was the only factor correlated with hospital death
      among 18 perioperative variables (p<0.006). HCA lasting > 55 minutes and a
      history of hypertension were associated with the development of TND (p<0.032 and
      p<0.02, respectively). CONCLUSIONS: Total arch replacement can be performed with
      acceptable mortality and neurological morbidity. Midterm survival is excellent in
      hospital survivors. The duration of HCA is not associated with in-hospital
      mortality when selective cerebral perfusion (either antegrade or retrograde) is
      used as an adjunct.

PMID- 12503040
TI  - A longitudinal study of the efficacy of interferon therapy in children with
      chronic hepatitis B.
AB  - BACKGROUND: Interferon alpha (IFN) is the most effective drug in the treatment of
      chronic hepatitis B. This article presents the results of IFN therapy and 28
      month follow-up. MATERIAL/METHODS: 193 Caucasian children (130 boys and 63 girls)
      aged 1.5-17 years were treated with IFN for 20 weeks (3.0 MIU 3 times a week).
      They were examined at baseline (period 0), after 6 weeks (period 1), 12 weeks
      (period 2), 20 weeks (period 3), 6 months (period 4), 12 months (period 5), 18
      months (period 6), and 24 months (period 7). RESULTS: HBcAg elimination drom
      period 3 was: 29.6%, 35.2%, 45.4%, 58.3%, in period 7 63.9% (significantly higher
      in girls). Significant positive correlations were found in several periods
      between IFN/m2 and HBeAg, HBsAg elimination, HBeAb, HBsAb presence and negatie
      correlations between IFN/m2 and ALT activity. ALT activity significantly
      decreased in girls between periods 0-3, in boys between 0-3 and 4-6. Significant
      positive correlations between ALT-0 and HBeAg, HBsAg elimination, HBeAb, HBsAb
      presence was seen in several periods, more frequently in girls. IFN transiently
      decreased Hb, leukocytes, and thrombocytes, especially in boys. No relationship
      was found between IFN therapy and bilirubin, protein, albumin and gammaglobulin
      concentrations. The prothrombin index increased after 6 months of IFN therapy in
      girls. CONCLUSIONS: The efficacy of IFN therapy is clearer with longer
      observation, especially in girls. A relationship was found between IFN dose and
      HBeAg/HbeAb and HBsAg/HBsAb seroconversion. IFN had a transient negative effect
      on the peripheral blood picture.

PMID- 12503041
TI  - Cytomegalovirus disease in neonates and infants--clinical presentation,
      diagnostic and therapeutic problems--own experience.
AB  - BACKGROUND: The aim of the study was to present diagnostic problems, different
      clinical presentations and results of treatment of cytomegalovirus infections in
      neonates and infants. MATERIAL/METHODS: The study was carried out in a group of
      31 children from 10 days to 12 months of age (17 boys, 14 girls). The diagnosis
      was based on serological investigations (presence of specific IgM antibodies
      and/or increasing titer of IgG antibodies), presence of intermediate or early CMV
      antigen in peripheral blood leukocytes or positive blood or urine PCR results.
      The treatment of 25 cases involved intravenous administration of gancyclovir at 5
      7 mg/kg daily doses for 14-21 days. In 1 case, hyperimmunized anti-CMV serum -
      Cytotect was used. RESULTS: The most common clinical symptoms were jaundice,
      hepato- and splenomegaly. Clinical investigations demonstrated increased
      aminotransferese activity and the signs of cholestasis. Other frequent findings
      included anemia, leukocytosis with atypical lymphocyte forms present, as well as
      thrombocytopenia. In majority treated patients, rapid regression of the clinical
      symptoms and normalization of transaminases activity was observed. Good outcome
      of the therapy was confirmed by immunological investigations. The effects of the
      terapy were similar irrespective of the dose and duration of gancyclovir
      treatment. The tolerance of the drug was good - no indications for
      discontinuation of the treatment were observed in any of the patients.
      CONCLUSIONS: The clinical presentations of cytomegalovirus disease in infants are
      varied, the diagnosis of the disease should be considered in children with
      persistent jaundice, especially if it is accompanied by hepatomegaly and
      increased aminotransferase activity or signs of cholestasis. Despite relatively
      good tolerance of the drug by children, the patients should be monitored for
      possible side effects, especially myelo- and nephrotoxic.

PMID- 12503042
TI  - Autoantibodies in children with chronic hepatitis B undergoing interferon
      therapy.
AB  - BACKGROUND: The occurrence of various side effects in patients treated with
      interferon alpha has attracted more attention to the manifestation of
      autoantibodies. The purpose of our study was to evaluate the side effects of
      interferon in children suffering from chronic hepatitis B by detecting six
      autoantibodies. MATERIAL/METHODS: Autoantibodies were examined in 76 children (55
      boys and 21 girls) aged 2-16 years, treated with interferon-alpha 3 MU 3 times
      weekly for 20 weeks. They were tested before treatment (exam I) and after its
      conclusion (exam II). SMAs were determined by indirect immunofluorescence
      (Euroimmuno reagents), while ANA, AMA M2, GPC, TPO and ATG were measured by EIA
      (Biomedica reagents). RESULTS: No statistically significant differences were
      found between the total number of patients with autoantibodies in examination I
      and examination II. A comparison of the frequency of presence or absence of
      autoantibodies in the same patients in exams I and II showed significantly more
      frequent disappearance of GPC in exam II than appearance (p<0.00005). This was
      also observed in the case of TPO (p=0.320). In relation to ANA, SMA, AMA M2 and
      ATG these differences were not significant. CONCLUSIONS: INF-alpha does not
      induce autoantibody formation in children with chronic hepatitis B. Our results
      suggest that IFN-alpha may inhibit the formation of some autoantibodies.

PMID- 12503043
TI  - Totally endoscopic bilateral internal thoracic artery bypass grafting in a young
      diabetic patient.
AB  - BACKGROUND: The introduction of robotics into cardiosurgical practice in 1998 has
      enabled totally endoscopic closed chest procedures. Totally endoscopic grafting
      of the LAD (TECAB) is no longer an experimental procedure. CASE REPORT: We report
      on a case with totally endoscopic bilateral internal thoracic artery bypass
      grafting to the left anterior descending and right coronary artery in a 36-year
      old obese female diabetic patient using the daVinci surgical system. The patient,
      suffering from juvenile diabetes for 26 years, presented with stable angina (CCS
      class II). A coronary angiogram revealed 2-vessel disease with a long complex
      proximal lesion of the left anterior descending artery (LAD) (90%) and 80%
      stenosis of the proximal right coronary artery (RCA). Due to the condition of the
      proximal LAD (high risk PTCA with rather poor prognosis), the patient was
      referred for minimally invasive operative revascularisation of the LAD and the
      RCA. After informed consent was obtained the patient underwent totally endoscopic
      double internal thoracic artery bypass revascularisation on the arrested heart
      using computer-enhanced telemanipulation technology. RESULTS: The feasibility and
      safety of successful closed chest, totally endoscopic double coronary bypass
      grafting with two internal thoracic arteries is demonstrated in this case.
      Preservation of a stable chest cavity and reduced risk for wound healing
      complications in diabetics with an excellent cosmetic result are the obvious
      advantages of the techniques described.

PMID- 12503044
TI  - Recombinant coagulation factor VIIa for rapid preoperative correction of warfarin
      related coagulopathy in patients with acute subdural hematoma.
AB  - BACKGROUND: Intracranial hemorrhage, either spontaneous or traumatic is a well
      known and potentially lethal complication of Warfarin treatment. Patients with
      Warfarin-related intracranial hemorrhage need urgent reversal of anticoagulation
      that must be especially rapid if surgical intervention is indicated. The
      traditional treatment with fresh frozen plasma (FFP) and vitamin K often fails to
      achieve the desired correction of coagulopathy in urgent neurosurgical settings.
      CASE REPORT: In the present case Recombinant Coagulation Factor VIIa (rFVIIa) was
      used for preoperative reversal of Warfarin-related coagulopathy. The patient was
      a fifty two years old man, mechanic valve recipient with Warfarin-induced
      coagulopathy: International Normalization Ratio (INR) of 6.39, who suffered from
      acute subdural hematoma and needed urgent neurosurgical intervention. He received
      a single dose of rFVIIa 120 mg/kg and immediately underwent craniotomy and
      evacuation of the hematoma. Appropriate hemostasis was achieved during surgery
      and coagulation test taken two hours after rFVIIa injection revealed INR of 1.25.
      The INR remained normalized for additional 14 hours. To the best of our
      knowledge, this is the first report on the use of rFVIIa in the preoperative
      management of Warfarin-induced intracranial hemorrhage. RESULTS: Recombinant
      Coagulation Factor VIIa provides rapid correction of coagulation to a level that
      allows safe neurosurgical intervention without significant delay. This agent is
      safe and effective; and should be considered for reversal of Warfarin-induced
      coagulopathy in cases of intracranial hemorrhage, especially when urgent surgical
      intervention is required.

PMID- 12503045
TI  - The ABCs of research on pulsatile versus nonpulsatile perfusion during
      cardiopulmonary bypass.
AB  - The literature suggests that pulsatile flow should be routinely used during
      cardiopulmonary bypass (CPB) in moderate- to high-risk cardiac surgery patients,
      especially those who must undergo more than 45 minutes of aortic crossclamping.
      Nevertheless, the use of pulsatile versus nonpulsatile perfusion remains
      controversial, mainly owing to a lack of precise, complete quantification of
      pressure-flow waveforms. This editorial briefly summarizes the major factors, or
      'basic ABCs, ' that affect the validity of research in this area. A. Because
      pulsatile flow depends on an energy gradient, investigators must quantify the
      difference in the hemodynamic energy levels produced by specific pulsatile and
      nonpulsatile pumps before meaningful direct comparison of these two perfusion
      modes can be possible. B. The energy equivalent pressure (EEP) formula should be
      used for this purpose. C. In conducting clinical trials of the perfusion modes,
      researchers must use appropriate patient-selection criteria, use pulsatile flow
      continuously during CPB, and choose extracorporeal-circuit components carefully.
      By following these basic ABCs, researchers will produce more valid and meaningful
      results that will translate into better outcomes for CPB patients.

PMID- 12503046
TI  - Detection of Cryptosporidium parvum infection in childhood using various
      techniques.
AB  - BACKGROUND: The protozoan parasite Cryptosporidium parvum, which causes acute
      gastroenteritis in both humans and animals, has become an important pathogen all
      over the world. C. parvum may cause asymptomatic or symptomatic acute infections
      of the digestive system in immunocompetent subjects, but life-threatening disease
      in immunocompromised hosts. The aim of this study was to determine the usefulness
      of conventional microscopic staining techniques in the detection of C. parvum.
      For this purpose, 50 unselected immunocompetent asymptomatic children were
      evaluated for C. parvum during routine upper endoscopy. MATERIAL/METHODS:
      Duodenal aspirates and duodenal biopsy samples from 37 girls and 13 boys, between
      the ages of 2 and 18 years, obtained by gastrointestinal upper endoscopy and
      concomitant stool samples were examined with different staining techniques.
      RESULTS: Two stool samples and one duodenal aspirate were positive for C. parvum,
      but we could not demonstrate C. parvum in any duodenal biopsy samples. Dyspepsia
      was the primary indication for upper endoscopy in the patient with positive
      duodenal aspirate sample. CONCLUSIONS: These findings indicate that there is a
      low asymptomatic carrier rate in immunocompetent subjects with no involvement of
      intestinal villius attachment in the duodenum. We also conclude that C. parvum is
      an infrequent parasite in asymptomatic subjects, most probably due to a very low
      prevalence of HIV positivity in Turkey.

PMID- 12503047
TI  - Psychosocial factors in chronic disability.
AB  - If adopted without adequate cause, the lifestyle of an invalid is a grave
      misfortune for the patient and for its reflection on current social attitudes
      that foster such states. Psychological illnesses are frequently invoked and are
      often a genuine source of suffering and disability. However, patients who may be
      rewarded by large financial settlements in courts, may also on occasion
      exaggerate their claims. Modern society has established systems of support, and
      rulings in court proceedings that conduce to illness behaviour. To some extent
      the portentous diagnostic labels given to these patients fosters rather than
      alleviates illness. It is probable that biological factors deriving from the
      primary event initiate the process. In medical terms, the symptoms and
      disabilities are often discrepant with the initial illness or injury. The
      patients' behaviour arises out of a desire to attain the sick role for secondary
      gain. If society eliminated the stigma of psychological illness, and opposed
      exaggeration and simulation of illness, then such chronic disability with
      'retreat into illness' might disappear. Sometimes an assumed illness becomes an
      adopted way of life. The unfortunate patients may come to believe they are ill;
      symptoms then persist after settlement. It is wrong to blame everything on
      society and to deny the free choice of the individual. Nevertheless, the
      pressures of society can be difficult to withstand for those not gifted with
      resilience. We should also recognise and try to eliminate the contribution made
      by doctors and health workers who mistakenly aid and abet a 'culture' that
      promotes this state of chronic disability. If adopted without adequate cause, the
      lifestyle of an invalid is a grave misfortune for the patient and for its
      reflection on current social attitudes that foster such states. Psychological
      illnesses are frequently invoked and are often a genuine source of suffering and
      disability. However, patients who may be rewarded by large financial settlements
      in courts, may also on occasion exaggerate their claims. Modern society has
      established systems of support, and rulings in court proceedings that conduce to
      illness behaviour. To some extent the portentous diagnostic labels given to these
      patients fosters rather than alleviates illness. It is probable that biological
      factors deriving from the primary event initiate the process. In medical terms,
      the symptoms and disabilities are often discrepant with the initial illness or
      injury. The patients' behaviour arises out of a desire to attain the sick role
      for secondary gain. If society eliminated the stigma of psychological illness,
      and opposed exaggeration and simulation of illness, then such chronic disability
      with 'retreat into illness' might disappear. Sometimes an assumed illness becomes
      an adopted way of life. The unfortunate patients may come to believe they are
      ill; symptoms then persist after settlement. It is wrong to blame everything on
      society and to deny the free choice of the individual. Nevertheless, the
      pressures of society can be difficult to withstand for those not gifted with
      resilience. We should also recognise and try to eliminate the contribution made
      by doctors and health workers who mistakenly aid and abet a 'culture' that
      promotes this state of chronic disability

PMID- 12503048
TI  - Leptin--from a signal of adiposity to a hormonal mediator in peripheral tissues.
AB  - The biology of leptin has been studied most extensively in the central nervous
      system for the regulation of food intake and energy balance. In recent years, a
      growing number of publications have reported several activities of this adipose
      secreted protein in different organs. These effects appear to be independent of
      the regulation of food intake or at least not directly correlated to it, but
      rather related to the hormonal regulation of these particular tissues. Thus
      leptin is now also considered to be a hormonal factor that informs several
      hormonal circuits and biological peripheral functions of the nutrition status of
      the organism. Different systems are involved in leptin activity, such as the
      pituitary, male and female reproductive organs, the mammary gland, the immune
      system, the gut, the kidney and the lung. Functional leptin receptors and/or
      leptin protein have been shown to be expressed in these tissues. Furthermore,
      interesting interactions have been reported with classical hormones involved in
      the regulation of activities in such organs. These observations give more
      detailed evidence of the relationship between nutrition and tissue
      differentiation in peripheral sites, possibly mediated by classical hormonal
      circuits. This work aims to review the most important functional findings on
      leptin's effects in these peripheral sites, and potential future studies are
      suggested, based on currently available data.

PMID- 12503050
TI  - Music as an aid in the development of the social self.
AB  - The development of the social self has been a topic of interest to developmental
      psychologists for some time. With the recent emphasis placed on the effect of the
      nuclear family and its increasing paucity, researchers have been even more
      pressed to develop alternate means to aid in the social effects of family and
      subsequently enhance a child's assertion of independence. In our paper we explore
      some of the possible ways by which developmental learning occurs, most notably by
      implicit or unconscious acquisition. We further provide some historical
      background explaining the emergence of this unconscious learning. Once we
      understand the process by which this learning occurs and the historical context
      in which it operates we can put forth our hypothesis. We suggest that an
      effective way of aiding or supplementing the role of the family is by providing a
      theoretical family unit. Specifically we propose that participation in musical or
      band related activities aids in the emergence of adolescence independence and a
      healthy self concept.

PMID- 12503049
TI  - Lectins as markers for blood grouping.
AB  - Lectins are unique proteins of varying biological importance. They are
      characterized by specific binding to carbohydrate residues, whether
      monosaccharides, disaccharides or polysaccharides. The sugar heads on the surface
      of the erythrocyte specify the different blood groups. Lectins, as an antigenic
      determinant of blood group, have come to be an important tool in the
      identification of different blood groups. A handful of lectins may be considered
      excellent reagents for anti-A, anti-B, anti-N etc, but the anti-A and anti-M are
      not yet regarded as commercially suitable antisera. Lectin from Vicia cracca has
      been proved to be a good anti-A, lectin from Dolichus biflorus can be used as
      anti-A1, and lectin from Griffonia simplicifolia as anti-B. Lectin from Vicia
      graminea is said to be a good typing reagent as Anti-N. On the other hand, the
      lectins involved in polyagglutination are absolutely essential as the reagent of
      choice and these cannot as yet be replaced by antibodies of any kind.
      Erythrocytes with exposed cryptantigens are significantly more sensitive to
      agglutination by certain lectins than by polyclonal antibodies. Peanut agglutinin
      (PNA), Polybrene, and Glycine max lectins are frequently used for the
      identification of different cryptantigens. The application of lectins as an anti
      B reagent has proven to be as useful as human polyclonal or mouse monoclonal
      antibodies. Besides their specificity, lectins are excellent reagents because of
      their lower cost and indigenous production. The importance of various lectins
      used as markers for blood grouping is discussed.

PMID- 12503052
TI  - Genetics and environmental factors in endocrine/organ-specific autoimmunity: have
      there been any major advances?

PMID- 12503053
TI  - The continuous discovery of autoantigens in endocrine organ-specific
      autoimmunity: do they help us to understand pathogenesis?

PMID- 12503054
TI  - Autoreactive T cells in endocrine/organ-specific autoimmunity: why has progress
      been so slow?
AB  - It has been generally accepted that T cells play a critical role in endocrine
      autoimmune diseases. Immunotherapy aimed at T cells usually intervenes in the
      disease process. Yet, it has proven very difficult to identify the pathogenic T
      cells. This is partly caused by lack of measures to detect autoreactive T cells
      in a specific, sensitive and reproducible fashion as is achievable for
      determination of autoantibodies. There are, however, more explanations for the
      perhaps disappointing progress in this area: unlike autoantibodies, the relevant
      (disease-associated) autoreactive T cells act in the tissue lesion, and only
      circulate in very low precursor frequencies. Moreover, T cell autoreactivity is
      counteracted by various mechanisms of immune regulation. Candidate target
      autoantigens of T cells have been identified by autoantibodies, while there is
      little evidence that these autoantibodies are pathogenic. It is therefore
      conceivable that additional T cell targets exist. Finally, results from
      experimental animal models of endocrine autoimmunity have raised false
      expectations. Nonetheless, significant progress in our understanding of the
      contribution of (autoreactive) T cells to organ-specific destruction and
      autoimmune disease has been achieved. Although cross-sectional detection of
      autoreactive T cells bears little relevance to diagnosis, longitudinal studies
      have proven useful in determining the fate of islet implantation in type 1
      diabetes patients, defined the immunological efficacy of immuno-intervention
      studies, and have led to definition of relevant target autoantigens and peptides
      that will help to monitor disease-associated autoimmunity. In conclusion,
      progress in the area of autoreactive T cells in the pathogenesis of type 1
      diabetes may have seemed slow in the eyes of the beholder, but in fact, studies
      on T cells have contributed significantly to the unravelling of the pathogenic
      processes leading to the definition of appropriate targets for immuno
      intervention.

PMID- 12503055
TI  - Are we ready to predict and prevent endocrine/organ specific autoimmune diseases?

PMID- 12503056
TI  - Animal models of endocrine/organ-specific autoimmune diseases: do they really
      help us to understand human autoimmunity?
AB  - Organ-specific or endocrine autoimmune diseases are complex, polygenic
      afflictions the penetrance of which is heavily dependent on various environmental
      influences. Important target tissues are the thyroid, the islets of Langerhans,
      gastric parietal cells and steroid-producing cells in the adrenal and ovary. The
      etiology of these diseases remains to be clarified. The pathogenesis is strongly
      associated with autoimmune phenomena. None of the current treatment approaches
      provides a cure; rather they represent replacement therapy. An important
      objective in the treatment of endocrine/organ-specific autoimmune diseases is the
      detection of individuals at risk for the development of such diseases and the
      development of interventions to prevent an outbreak of the diseases. This
      requires an exquisite knowledge of the early etio-pathogenic stages of these
      diseases. This review concentrates on the usefulness of animal models for a
      precise understanding of these very early stages. It must be emphasized that
      studying animal models cannot answer all the problems presented by
      endocrine/organ-specific autoimmune diseases as seen in the clinic. It must be
      expected - considering the different etiologies in the different animal models
      (see below) - that the causes of the diseases in the human and the involvement of
      various genes and environmental factors may also vary. Yet, particularly in the
      study of the pre-autoimmune phases of the diseases, there is hardly any
      alternative to the study of animal models. Only limited series of experiments can
      be carried out in human subjects at risk to develop such diseases. Moreover, a
      general semblance (blueprint) of the etio-pathogenesis found in the animal models
      can lead the way for human studies. Efforts to understand the patho-physiology of
      the early stages of endocrine/organ-specific autoimmune diseases have mainly
      involved animal models that "spontaneously" develop such diseases. Of these the
      bio-breeding diabetes-prone (BB-DP) rat and the non-obese diabetes (NOD) mouse
      are the most well studied, yet many studies have also been carried out in the
      obese strain (OS) chicken. Apart from these spontaneous models there are animal
      models that are induced by environmental perturbations (viruses, toxic
      substances), by thymectomy procedures or by genetic manipulations, e.g., the RIP
      LCMV model and the BDC 2.5 TCR mouse model. A general blueprint has emerged from
      the studies into the early stages of the pathogenesis of endocrine/organ-specific
      autoimmune diseases in these animal models: animals at risk to develop
      endocrine/organ-specific autoimmune diseases show various pre-autoimmune
      aberrancies in their target glands, T cells, macrophages (Mphi) and dendritic
      cells (DC). The presumably aberrant target cells, T cells, DC and Mphi need to
      interact abnormally before autoimmune disease can fully develop. In this abnormal
      interaction additional aberrancies in other regulatory systems may play a role in
      a further exacerbation of the self-directed immune response, such as defects in
      the hypothalamus pituitary adrenal (HPA) axis system. The various aberrancies are
      partly genetically determined by a variety of separate genes, particularly MHC
      related genes, but they may also be environmentally induced (e.g., via viruses,
      high iodine diet, and other experimental manipulations). Recently evidence has
      been gathered for pre-autoimmune aberrancies similar to the animal models in the
      DC/ Mphi compartment and the HPA axis in humans at risk to develop
      endocrine/organ-specific autoimmune diseases. However, analogous pre-autoimmune
      abnormalities in human target glands or in T cell function have not yet been
      found with certainty. We believe that animal models of endocrine/organ-specific
      autoimmune disease still hold immense promise for the discovery of pathways,
      genes and environmental factors that determine the development of endocrine/organ
      specific autoimmune diseases. Animals affected by such diseases provide a unique
      opportunity to uncover disease-associated pathways, which are complicated to
      define in man.

PMID- 12503057
TI  - What can the epidemiological approach to type 1 diabetes contribute to the
      unravelling of autoimmune pathological mechanisms?

PMID- 12503058
TI  - Is it cytotoxicity or apoptosis which causes cell death in autoimmunity?

PMID- 12503060
TI  - Inside-Out versus Outside-In models for virus induced demyelination: axonal
      damage triggering demyelination.
AB  - The primary target in multiple sclerosis (MS) is believed to be either myelin
      itself (myelinopathy) or the myelin-forming cell, the oligodendrocyte
      (oligodendrogliopathy). Although axonal injury occurs in MS, it is regarded as a
      secondary event to the myelin damage. Here, the lesion develops from myelin
      (outside) to the axon (inside) (Outside-In model). Recently, gray matter lesions
      and axonal injury in normal-appearing white matter have also been reported in MS.
      This raises two questions. 1) Is axonal injury exclusively secondary to myelin
      damage or from a direct insult to the axon or neurons (axonopathy)? (2) Is the
      injured axon regarded as only an end result of pathology or disease, or can
      axonal injury contribute to the spread of secondary damage, including
      demyelination? The former is raised from the fact that axonal damage has been
      reported in several virus infections, including human immunodeficiency virus,
      human T-lymphotropic virus 1, herpes simplex virus and coronavirus, which also
      cause demyelination. The latter possibility where axonal injury leads to other
      changes is raised from the rather unexpected similarity between spinal cord
      injury (SCI) and MS where axonal injury, oligodendrocyte apoptosis and
      demyelination are all present. In SCI, transection of axons leads to delayed
      oligodendrocyte apoptosis with secondary demyelination. Neurofilament
      immunostaining of spinal cord sections demonstrates that axonal injury with
      oligodendrocyte apoptosis also precedes demyelination in an animal model for MS,
      Theiler's murine encephalomyelitis virus infection. This implies that axonal
      injury could trigger demyelination. In this instance, lesions develop from the
      axon (inside) to the myelin (outside) (Inside-Out model).

PMID- 12503061
TI  - Modulation of immune functions by measles virus.
AB  - Measles virus remains among the most potent global pathogens killing more than 1
      million children annually. A profound suppression of general immune functions
      occurs during and for weeks after the acute disease, which favors secondary
      infections. In contrast, virus-specific immune responses are efficiently
      generated, mediate viral control and clearance and confer a long-lasting
      immunity. Because they sense pathogen-associated molecular patterns, and
      subsequently initiate and shape adaptive immune responses, professional antigen
      presenting cells (APC) such as dendritic cells are likely to play a key role in
      the induction and quality of the virus-specific immune response. Key features of
      immune suppression associated with measles virus, however, are compatible with
      interference with APC maturation and function and subsequent qualitative and
      quantitative alterations of T cell activation.

PMID- 12503062
TI  - Heterologous immunity and the CD8 T cell network.

PMID- 12503063
TI  - Human cytomegalovirus and immunopathology.

PMID- 12503064
TI  - Human parvovirus B19-induced cell cycle arrest and apoptosis.

PMID- 12503065
TI  - Immunopathology during coxsackievirus infection.

PMID- 12503066
TI  - Nipah virus infection, an emerging paramyxoviral zoonosis.
AB  - The Nipah virus outbreak represented one of several bat-derived paramyxoviruses
      that has emerged during the last decade to cause severe human and animal disease.
      The pathogenesis of Nipah infection is associated with its ability to infect
      blood vessels and extravascular parenchyma in many organs, particularly in the
      central nervous system. The clinical manifestations of acute Nipah infection
      range from fever and mild headache to a severe acute encephalitic syndrome in
      which there is a high mortality. Much remains to be understood about this new
      disease, including its intriguing ability to cause relapsing encephalitis in some
      survivors. This review provides an overview of the Nipah outbreak, focussing on
      what is presently known about it as an infectious disease, including the clinical
      aspects, pathology and pathogenesis.

PMID- 12503068
TI  - Menopause: social expectations, women's realities.
AB  - The experience of menopause, and the ramifications of that experience for
      psychiatric treatment, is significantly shaped by social and historical context
      and by the implicit and explicit expectations they arouse in women. American
      society is heavily youth-oriented. Although in fact many women experience this
      time as one of liberation and self-actualization, society views them as bereft of
      their families and devoid of sexual interest. Their expectations for their social
      roles at this time of life may not comport with those of their children. The
      emphasis on hormone treatment, incorrectly termed "replacement," has exacerbated
      women's fears of aging.

PMID- 12503069
TI  - Anticipations and experiences of menopause in a Danish female general population
      cohort born in 1936.
AB  - INTRODUCTION: Few studies on menopause consider the impact of sociopsychological
      factors on women's experiences of menopause. OBJECTIVE: To focus on women's
      experiences of menopause: complaints, health, attitudes and stereotypes of
      menopause and ageing. DESIGN: Prospective population study, initiated in 1976
      with follow-ups in 1981, 1987 and 1996 with a high participation rate, a
      representative sample of all women born in 1936 and living in the County of
      Copenhagen. STUDY METHODS: Questionnaires and personal interviews:
      sociodemographic data, menopause, general health, sexuality, ageing. RESULTS: The
      strongest predictors of the way in which women experienced menopause, including
      sexuality, were their general health earlier in life, their social circumstances
      and their expectations of menopausal changes. The biological changes had
      significant correlation to hot flushes. Menopause was seen as a symbol of ageing.
      Only a minority suffered from serious problems, typically originating earlier in
      life.

PMID- 12503070
TI  - The effects of the menopausal transition and biopsychosocial factors on well
      being.
AB  - OBJECTIVE: The aim of this study was to determine whether women's well-being
      changed with the menopausal transition, and the effect on well-being of other
      biological, psychosocial and lifestyle factors. METHOD: A longitudinal
      observational study was carried out utilising a population-based sample of 438
      mid-aged, Australian- born women. A total of 9 assessments were made at annual
      intervals. Mood was measured using the Affectometer 2. Mood, menopausal status,
      psychosocial and lifestyle variables and hormone levels were determined annually.
      226 subjects who transited the natural menopausal transition were included in the
      analysis. RESULTS: As women pass from early in the menopausal transition to later
      in the transition, reporting at least 3 months of amenorrhoea, negative mood
      declines significantly, positive mood does not change and well-being
      significantly improves. Well-being scores are highly correlated over time, with
      early scores having a major effect on later scores. Well-being is also
      significantly affected by changes in marital status, work satisfaction, daily
      hassles and life events. CONCLUSIONS: Well-being improves as women enter the
      later stages of the menopausal transition and is also influenced significantly by
      psychosocial factors.

PMID- 12503071
TI  - Description of women's personality traits and psychological vulnerability prior
      to choosing hormone replacement therapy.
AB  - INTRODUCTION: Data suggest that women using hormone replacement therapy (HRT)
      represent a special subgroup of the general population regarding, for instance,
      cardiovascular risk factors and education. OBJECTIVE: To analyse if women who
      choose HRT are characterised a priori by high neuroticism score or by
      psychological vulnerability. DESIGN: A prospective population-based study was
      initiated in 1976 with follow-ups in 1981, 1987 and 1996. The population
      comprises a random sample of 621 women born in 1936 and living in the county of
      Copenhagen. STUDY METHODS: The analyses are based on data on two sub-cohorts of
      268 and 235 women from the large population-based study. These subgroups consist
      of the women participating in both baselines at 40 and 45 years respectively and
      at follow-up in 1996. At the age of 40 the women participated in a comprehensive
      examination, which apart from baseline characteristics included Eysencks
      personality questionnaire concerning intro/extroversion and neuroticism. At the
      age of 45, the re-examination of the women included a test for psychological
      vulnerability. The participants reported whether or not they used HRT at the age
      of 40, 45, 51 and 60 years. The analyses comprised "never users" of HRT and
      "future users", defined as women who started HRT subsequent to baseline
      registration during the observation period. The groups were compared by
      multivariate statistical methods to adjust for confounding factors. RESULTS:
      Women with high neuroticism score at the age of 40 were more likely to become
      users of HRT in the future compared to women with low neuroticism score. At the
      age of 45, psychologically vulnerable women were more likely to become users of
      HRT in the future compared to non-vulnerable women. The associations became
      insignificant when correcting for potential confounders. The study suggests that
      selection bias among women choosing HRT may also include personality traits.

PMID- 12503072
TI  - The hormone replacement therapy controversy.
AB  - The issue of hormone replacement treatment for menopausal symptoms, osteoporosis,
      various cardiac problems, and other disorders has received a great deal of
      attention. Recent data concerning the benefits and risks have changed ideas about
      indications and contra-indications. In this paper we will consider the multiple
      factors that determine an individual woman's decision about taking or continuing
      to take hormone replacement therapy, not only the medical indications. We will
      discuss the established benefits of replacement therapy, conditions for which the
      benefits are not established, areas of controversy, risks of treatment, and
      factors underlying the decisions about undergoing the treatment.

PMID- 12503073
TI  - A non-Darwinian role for mutagenesis in stem cell-derived cancers.
AB  - It is clear that mutations cause cancer. The implicated mechanism is Darwinism.
      That is, a stochastic series of mutations is purported to effect the cellular
      variability upon which natural selection acts to yield increasingly cancer-like
      intermediates leading ultimately to malignant clones. It is no wonder then that
      the neoplastic phenotype is considered "alien," having evolved via random
      unrehearsed events. Neoplasia, however, has also been depicted as something less
      than foreign, bordering on familiar. This is because cancer shares proliferative
      and invasive qualities with the native developmental processes of embryogenesis
      and adult tissue renewal/repair. A question then arises: If key features of
      malignancy already naturally exist within well-choreographed programs, why
      reinvent this phenotype via stochastic multistep schemes rather than reactivate
      it largely en bloc? Indeed, as will be shown, tissues do harbor a malignant
      potential capable of reactivation. Specifically, this capability is maintained by
      stem cells (having inherited such from embryonic precursors)-a phenotype
      controlled by a microenvironment favoring perpetual rearing by (quiescent) stem
      cells of proliferative progeny for orderly renewal over neoplasia. Accordingly,
      normally well-sequestered stem cells, when amid carcinogen/mutagen-induced
      disruption to local surroundings, produce progeny tending by default toward
      disorderliness (neoplasia) over renewal. Because such tumor-causing mutations act
      non-cell autonomously, this cancerous state is potentially reversible but
      subsequent cell-autonomous mutations can impair particular clonal progeny,
      already cancerous, from regressing. Thus, a scenario wherein mutations (1) de
      repress malignancy non-cell autonomously and then (2) slow its reversion cell
      autonomously, commonly misinterpreted as Darwinian, may constitute a non
      Darwinian mechanism for the genesis of cancers that are stem cell derived.

PMID- 12503074
TI  - Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p
      correlating with loss in chromosome 10q.
AB  - Various genomic alterations have been detected in glioblastoma. Chromosome 7p,
      with the epidermal growth factor receptor locus, together with chromosome 10q,
      with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in
      malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent
      kinase inhibitor 2A locus, are among the most frequently damaged chromosomal
      regions in glioblastoma. In this study, we evaluated the genetic status of 32
      glioblastomas by comparative genomic hybridization; the sensitivity of
      comparative genomic hybridization versus differential polymerase chain reaction
      to detect deletions at the phosphatase and tensin homologue deleted in chromosome
      10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A
      loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of
      genetic lesions (gain or loss) at 16 different selected loci (including
      oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13
      different chromosomes; and the possible existence of a statistical association
      between any pair of molecular markers studied, to subdivide the glioblastoma
      entity molecularly. Comparative genomic hybridization showed that the most
      frequent region of gain was chromosome 7p, whereas the most frequent losses
      occurred on chromosomes 10q and 13q. The only statistically significant
      association was found for 7p gain and 10q loss.

PMID- 12503075
TI  - Reduced expression of p27kip1 and increased hepatocyte proliferation in p53
      deficient mice.
AB  - Livers from wild-type and p53-deficient mice were analyzed for the expression of
      cell-cycle regulatory proteins in an attempt to determine the mechanism for the
      increased proliferation of liver cells in p53-deficient mice associated with
      enhanced susceptibility to aflatoxin-induced liver cancer. The most striking
      difference found was a significant reduction of the cyclin-dependent kinase
      inhibitor p27(kip1) in the livers of 3-mo-old p53-/- mice, whereas only small
      changes were found in the expression of cyclins, cyclin-dependent kinases, and
      the inhibitors p21(cip1) and p16(ink4a). Relative to wild-type liver, the amounts
      of p27(kip1) mRNA were reduced at both 1 and 3 mo, whereas the levels of
      p27(kip1) protein were decreased only at 3 mo. These results identify an
      uncharacterized link between the expression of p53 and p27(kip1) that may involve
      both transcriptional and post-transcriptional regulation and allow hepatocytes to
      continue to proliferate after 3 wk of age. We postulate that this increased
      proliferation leads to increased susceptibility to aflatoxin-induced
      hepatocarcinogenesis.

PMID- 12503076
TI  - DNA repair gene O6-methylguanine-DNA methyltransferase: promoter hypermethylation
      associated with decreased expression and G:C to A:T mutations of p53 in brain
      tumors.
AB  - The DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) removes
      alkylating adducts from the O(6) position of guanine and protects cells from
      cytotoxic and mutagenic effects. Expression of MGMT is decreased in some cancers,
      which may be the result of methylation of CpG islands of both the promoter and
      coding regions of the gene. We studied the methylation status of the MGMT
      promoter in a very large collection of brain tumors (85) using methylation
      specific polymerase chain reaction (PCR). Aberrant methylation occurred in 48% of
      85 human brain tumor samples. Quantitative real-time PCR showed that expression
      of MGMT mRNA levels was significantly decreased (P < 0.001) in those brain tumors
      that had methylation of the promoter region of their MGMT gene. MGMT can prevent
      G to A mutations by removing alkyl groups from the O(6) position of guanine. We
      found a significantly increased frequency of G:C to A:T mutations of the p53 gene
      in brain tumors having a methylated MGMT promoter compared with those having an
      unmethylated MGMT promoter (P < 0.05), and all the non-CpG dinucleotide G:C to
      A:T mutations of p53 were in samples with a methylated MGMT promoter.

PMID- 12503077
TI  - Alterations of the M6p/Igf2 receptor gene in lung adenocarcinomas induced by N
      nitrosobis(2-hydroxypropyl)amine in rats.
AB  - Alterations of the mannose 6-phosphate/insulin-like growth factor II receptor
      (M6p/lgf2r) gene were investigated in lung adenocarcinomas induced by N
      nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 wk old, were
      given 2000 ppm BHP in their drinking water for 12 wk and maintained without
      further treatment until killed at week 25. A total of 12 lung adenocarcinomas
      were obtained, and total RNAs were extracted from each for assessment of
      mutations and levels of aberrant transcripts of the M6p/Igf2r gene by reverse
      transcription (RT)-polymerase chain reaction (PCR) single-strand conformation
      polymorphism analysis and RT-PCR analysis, respectively. No mutations were found
      in exons 27, 28, 31, 33, and 34. Aberrant transcripts bearing deletions of nt
      3698 to 4902, 3366 to 4902, and 3817 to 4697 were detected in three of 12
      adenocarcinomas (25%). These results suggest that alterations of the M6p/Igf2r
      gene may be involved in the development of lung adenocarcinomas induced by BHP in
      rats.

PMID- 12503078
TI  - Association of JNK1 with p21waf1 and p53: modulation of JNK1 activity.
AB  - Exposure of mammalian cells to genotoxic stress results in activation of the c
      jun amino-terminal kinase (JNK)-stress-activated protein kinase (SAPK) pathway
      and induction of DNA repair enzymes and cell cycle-regulatory proteins such as
      p53 and p21waf1. The p53 tumor suppressor protein transmits signals that activate
      p21waf1 gene expression. The p21waf1 protein then restricts cell-cycle
      progression, thereby allowing time for DNA repair to occur. In this study, we
      investigated the effects of modulation of the level of wild-type and mutant p53
      protein on basal JNK1 activity in the A1-5 rat fibroblast cell line. This cell
      line contains a p53 gene coding for a temperature-sensitive p53 protein, which
      allows us to regulate the relative level of wild-type and mutant p53 protein
      produced in cells. Using the immune complex kinase assay to measure JNK1
      activity, we demonstrated that cells expressing the wild-type-conformation p53
      protein (when grown at 32.5 degrees C) exhibited a very low level of JNK1
      activity. When cells were grown at 37 degrees C or 39 degrees C to express
      predominantly mutant p53 protein, basal level of JNK1 activity was significantly
      higher than at 32.5 degrees C. We also demonstrated protein-protein interactions
      between the p53, p21waf1, and JNK1 proteins in this cell line. Both wild-type p53
      protein (expressed at 32.5 degrees C) and mutant p53(val135) protein (expressed
      at 37 degrees C and 39 degrees C) were present in immunocomplexes of JNK1
      protein. Under conditions where wild-type p53 protein was present to induce
      p21waf1 expression (at 32.5 degrees C), a higher level of p21waf1 protein was
      also detected in the JNK1 immunocomplexes than in those at 37 degrees C and 39
      degrees C. We next investigated the effect that co-association of p53 protein and
      p21waf1 protein would have on JNK1 activity. We measured basal levels of JNK1
      activity in cells expressing wild-type p53 and p21waf1, or in p21waf1-null cells,
      and demonstrated that cells expressing both p53 and p21waf1 proteins exhibited an
      approximately threefold lower basal level of JNK1 activity when compared with
      p21waf1-null cells. To confirm that p21waf1 protein expression in cells resulted
      in reduced JNK1 activity, we transfected p21waf1-/- cells with a p21waf1
      expression vector. We observed that JNK1 activity was inhibited after exogenous
      p21waf1 protein was expressed in these cells. Our results provide evidence for
      modulation of the JNK1 pathway by p53 and p21waf1 proteins and support the
      hypothesis that modulation of JNK1 activity occurred through protein-protein
      interactions between JNK1, p53, and p21waf1 proteins.

PMID- 12503080
TI  - Statistical morphological analysis of hippocampal principal neurons indicates
      cell-specific repulsion of dendrites from their own cell.
AB  - Traditionally, the sources of guidance cues for dendritic outgrowth are mainly
      associated with external bodies (A) rather than with the same neuron from which
      dendrites originate (B). To quantify the relationship between factors A and B as
      determinants of the adult dendritic shape, the morphology of 83 intracellularly
      characterized, stained, completely reconstructed, and digitized principal neurons
      of the rat hippocampus was statistically analyzed using Bayesian optimization. It
      was found that the dominant directional preference (tropism) manifested in
      dendritic turns is to grow away from the soma rather than toward the incoming
      fibers or in any other fixed direction; therefore, B is predominant. Results are
      robust and consistent for all examined morphological classes (dentate gyrus
      granule cells, basal and apical trees of CA3 and CA1 pyramidal cells). In
      addition, computer remodeling of neurons based on the measured parameters
      produced virtual structures consistent with real morphologies, as confirmed by
      measurement of several global emergent parameters. Thus, the simple description
      of dendritic shape based on dendrites' tendency to grow straight, away from their
      own soma, and with additional random deflections, proves remarkably accurate and
      complete. Although based on adult neurons, these results suggest that dendritic
      guidance during development may be associated primarily with the host cell. This
      possibility challenges the traditional concept of dendritic guidance: in that
      hippocampal cells are densely packed and have highly overlapping dendritic
      fields, the somatodendritic repulsion must be cell specific. Plausible mechanisms
      involving extracellular effects of spikes are discussed, together with feasible
      experimental tests and predicted results.

PMID- 12503079
TI  - Novel functional interactions between Trk kinase and p75 neurotrophin receptor in
      neuroblastoma cells.
AB  - To understand the functional interactions between the TrkA and p75 nerve growth
      factor (NGF) receptors, we stably transfected LAN5 neuroblastoma cells with an
      expression vector for ET-R, a chimeric receptor with the extracellular domain of
      the epidermal growth factor receptor (EGFR), and the TrkA transmembrane and
      intracellular domains. EGF activated the ET-R kinase and induced partial
      differentiation. NGF, which can bind to endogenous p75, did not induce
      differentiation but enhanced the EGF-induced response, leading to differentiation
      of almost all cells. A mutated NGF, 3T-NGF, that binds to TrkA but not to p75 did
      not synergize with EGF. Enhancement of EGF-induced differentiation required at
      least nanomolar concentrations of NGF, consistent with the low-affinity p75
      binding site. EGF may induce a limited number of neuronal cells because it also
      enhanced apoptosis. Both NGF and a caspase inhibitor reduced apoptosis and,
      thereby, enhanced differentiation. NGF seems to enhance survival through the
      phosphatidylinositol-3 kinase (PI3K) pathway. Consistent with this hypothesis,
      Akt, a downstream effector of the PI3K pathway, was hyperphosphorylated in the
      presence of EGF+NGF. These results demonstrate that TrkA kinase initiates
      differentiation, and p75 enhances differentiation by rescuing differentiating
      cells from apoptosis via the PI3K pathway. Even though both EGF and NGF are
      required for differentiation of LAN5/ET-R cells, only NGF is required for
      survival of the differentiated cells. In the absence of NGF, the cells die by an
      apoptotic mechanism, involving caspase-3. An anti-p75 antibody blocked the
      survival effect of NGF. Brain-derived neurotrophic factor also enhanced cell
      survival, indicating that in differentiated cells, NGF acts through the p75
      receptor to prevent apoptosis.

PMID- 12503081
TI  - Overexpression of nPKC theta is inhibitory for agrin-induced nicotinic
      acetylcholine receptor clustering in C2C12 myotubes.
AB  - Protein kinase C (PKC) activity has been implicated in nicotinic acetylcholine
      receptor (nAChR) cluster disruption but the specific PKC isoforms involved have
      not been identified. We first tested whether phorbol esters, which activate PKCs,
      regulate agrin-induced nAChR clustering in C(2)C(12) cells. We found that
      extended phorbol ester treatment (6 hr) increased nAChR clustering by two-fold.
      This increase correlated in time with downregulation of PKCs, as indicated by the
      disappearance of cPKC alpha, suggesting that the presence of PKCs is inhibitory
      for maximal nAChR clustering. To address the question whether nPKC theta, a
      specific PKC isoform restricted in expression to skeletal muscle and localized to
      neuromuscular junctions, regulates agrin-induced nAChR cluster formation we
      overexpressed an nPKC theta -green fluorescent protein (GFP) fusion protein in
      C(2)C(12) myotubes. The number of nAChR clusters was significantly reduced in
      nPKC theta-GFP compared to GFP overexpressing myotubes at less-than-maximal
      clustering concentrations of agrin. These data indicate that nPKC theta activity
      inhibits nAChR cluster formation. To examine whether nPKC theta activation by
      phorbol esters regulates agrin-induced nAChR clustering, we treated
      overexpressing myotubes overnight with maximal agrin concentrations followed by
      phorbol esters for 1 hr. Phorbol ester treatment reduced preexisting nAChR
      cluster numbers in nPKC theta-GFP compared to GFP-overexpressing myotubes,
      suggesting that stimulating nPKC theta activity disrupts nAChR clusters in the
      presence of maximal clustering concentrations of agrin. Together these findings,
      that nPKC theta activity inhibits agrin-induced nAChR cluster formation and
      disrupts preexisting agrin-induced nAChR clusters, suggest that nPKC theta
      activity is inhibitory for agrin function.

PMID- 12503082
TI  - Selective changes in the neurofilament and microtubule cytoskeleton of NF-H/LacZ
      mice.
AB  - This study focused mainly on changes in the microtubule cytoskeleton in a
      transgenic mouse where beta-galactosidase fused to a truncated neurofilament
      subunit led to a decrease in neurofilament triplet protein expression and a loss
      in neurofilament assembly and abolished transport into neuronal processes in
      spinal cord and brain. Although all neurofilament subunits accumulated in
      neuronal cell bodies, our data suggest an increased solubility of all three
      subunits, rather than increased precipitation, and point to a perturbed filament
      assembly. In addition, reduced neurofilament phosphorylation may favor an
      increased filament degradation. The function of microtubules seemed largely
      unaffected, in that tubulin and microtubule-associated proteins (MAP) expression
      and their distribution were largely unchanged in transgenic animals. MAP1A was
      the only MAP with a reduced signal in spinal cord tissue, and differences in
      immunostaining in various brain regions corroborate a relationship between MAP1A
      and neurofilaments.

PMID- 12503083
TI  - Traumatic brain injury-induced acute gene expression changes in rat cerebral
      cortex identified by GeneChip analysis.
AB  - Proper CNS function depends on concerted expression of thousands of genes in a
      controlled and timely manner. Traumatic brain injury (TBI) in mammals results in
      neuronal death and neurological dysfunction, which might be mediated by altered
      expression of several genes. By employing a CNS-specific GeneChip and real-time
      polymerase chain reaction (PCR), the present study analyzed the gene expression
      changes in adult rat cerebral cortex in the first 24 hr after a controlled
      cortical impact injury. Many functional families of genes not previously
      implicated in TBI-induced brain damage are altered in the injured cortex. These
      include up-regulated transcription factors (SOCS-3, JAK-2, STAT-3, CREM, IRF-1,
      SMN, silencer factor-B, ANIA-3, ANIA-4, and HES-1) and signal transduction
      pathways (cpg21, Narp, and CRBP) and down-regulated transmitter release
      mechanisms (CITRON, synaptojanin II, ras-related rab3, neurexin-1beta, and
      SNAP25A and -B), kinases (IP-3-kinase, Pak1, Ca(2+)/CaM-dependent protein
      kinases), and ion channels (K(+) channels TWIK, RK5, X62839, and Na(+) channel
      I). In addition, several genes previously shown to play a role in TBI
      pathophysiology, including proinflammatory genes, proapoptotic genes, heat shock
      proteins, immediate early genes, neuropeptides, and glutamate receptor subunits,
      were also observed to be altered in the injured cortex. Real-time PCR analysis
      confirmed the GeneChip data for many of these transcripts. The novel
      physiologically relevant gene expression changes observed here might explain some
      of the molecular mechanisms of TBI-induced neuronal damage.

PMID- 12503084
TI  - Peroxynitrite generated in the rat spinal cord induces oxidation and nitration of
      proteins: reduction by Mn (III) tetrakis (4-benzoic acid) porphyrin.
AB  - To determine whether peroxynitrite at the concentration and duration present
      after spinal cord injury induces protein oxidation and nitration in vivo, the
      peroxynitrite donor 3-morpholinosydnonimine (SIN-1) was administered into the
      gray matter of the rat spinal cord for 5 hr. The cords were removed at 6, 12, 24,
      and 48 hr after SIN-1 exposure, immunohistochemically stained with antibodies to
      dinitrophenyl (DNP) and nitrotyrosine (Ntyr), markers of protein oxidation and
      nitration, respectively, and the immunostained neurons were counted. The
      percentages of DNP-positive (P = 0.023-0.002) and Ntyr-positive (P < 0.001 for
      all) neurons were significantly higher in the SIN-1-exposed groups than in the
      ACSF controls at each time, suggesting that peroxynitrite induced intracellular
      oxidation and nitration of proteins. The percentages of DNP- and Ntyr-positive
      neurons were not significantly different over time in either SIN-1- or ACSF
      exposed groups (P = 0.20-1.00). The percentage of DNP-positive neurons was 7.6 +/
      3% to 12 +/- 4.2% at 6-24 hr, and it was 14 +/- 2% to 19 +/- 2% at 6-24 hr for
      Ntyr-positive neurons after SIN-1-exposure, whereas both ranged over 2-3% in ACSF
      controls. Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP, a broad-spectrum
      scavenger of reactive species) significantly reduced the percentages of DNP- and
      Ntyr-positive neurons (P = 0.04 and 0.002, respectively) compared to a SIN-1
      exposed, untreated group at 24 hr after SIN-1 exposure. There were no significant
      differences between MnTBAP-treated and ACSF controls (P = 0.7 for DNP and 0.2 for
      Ntyr). These results further demonstrate peroxynitrite-induced protein oxidation
      and nitration and the efficiency of MnTBAP in scavenging peroxynitrite.

PMID- 12503085
TI  - Ciliary neurotrophic factor overexpression in neural progenitor cells (ST14A)
      increases proliferation, metabolic activity, and resistance to stress during
      differentiation.
AB  - Neurotrophic factors exert considerable neuroprotective and neurorestorative
      effects in neurodegenerative diseases. Because neuronal progenitor cells have, at
      least in part, the potency to restore degenerated neuronal networks, transgenic
      high-dosage expression of neurotrophins by these cells in neurotransplantation
      may be advantageous. In the present study, a retroviral vector containing the
      gene of rat ciliary neurotrophic factor (rCNTF) was permanently transfected into
      a striatal neuronal progenitor cell line. Qualitative and quantitative analyses
      demonstrated a sustained expression of the transgene; i.e., rCNTF was present at
      the mRNA level and protein level. Moreover, cocultivation in separate chambers of
      transgenic CNTF-ST14A cells and CNTF-dependent TF1 cells exerted typical
      biological effects, such as increased proliferation and differentiation of the
      TF1 cells, indicating the functional integrity of the secreted recombinant
      neurotrophin. The CNTF-ST14A cells displayed improved stress response compared
      with native ST14A cells under differentiation conditions, i.e., at the
      nonpermissive temperature of 39 degrees C and after staurosporine exposure,
      respectively. This effect coincided with a relatively reduced apoptosis rate and
      a raised metabolic activity of CNTF-ST14A cells at 39 degrees C.
      Neurotransplantation of CNTF-ST14A cells in the rat quinolinic acid model of
      Huntington's disease showed a significant and sustained decline in pathological
      apomorphine-induced rotations compared with parental ST14A cells. We conclude
      that sustained functional transgene CNTF production improves stress response as
      well as metabolic activity, making CNTF-ST14A cells a promising tool for
      neurotransplantation in the quinolinic acid model of Huntington's disease.

PMID- 12503086
TI  - Mature myelin basic protein-expressing oligodendrocytes are insensitive to
      kainate toxicity.
AB  - We examined the vulnerability to excitotoxicity of rat oligodendrocytes in
      dissociated cell culture at different developmental stages. Mature
      oligodendrocytes that express myelin basic protein were resistant to excitotoxic
      injury produced by kainate, whereas earlier stages in the oligodendrocyte lineage
      were vulnerable to this insult. To test the hypothesis that the sensitivity of
      immature oligodendrocytes and the resistance of mature oligodendrocytes to
      kainate toxicity were due to differences in membrane responsiveness to kainate,
      we used whole-cell patch-clamp recording. Oligodendrocyte precursors in cultures
      vulnerable to kainate toxicity responded to 500 microM kainate with large inward
      currents, whereas mature myelin basic protein-expressing oligodendrocytes in
      cultures resistant to kainate toxicity showed no clear response to application of
      this agonist. We assayed expression of glutamate receptor subunits (GluR) -2, -4,
      -6, -7, and KA2 using immunoblot analysis and found that expression of all of
      these glutamate receptors was significantly down-regulated in mature
      oligodendrocytes. These results suggest a striking developmental regulation of
      glutamate receptors in oligodendrocytes and suggest that the vulnerability of
      oligodendrocytes to non- N-methyl-D-aspartate receptor-mediated excitotoxicity
      might be much greater in developing oligodendrocytes than after the completion of
      myelination.

PMID- 12503087
TI  - Inhibition of glial cell proinflammatory activities by peroxisome proliferator
      activated receptor gamma agonist confers partial protection during antimyelin
      oligodendrocyte glycoprotein demyelination in vitro.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the
      nuclear hormone superfamily originally characterized as a regulator of adipocyte
      differentiation and lipid metabolism. In addition, PPAR-gamma has important
      immunomodulatory functions. If the effect of PPAR-gamma's activation in T-cell
      mediated demyelination has been recently demonstrated, nothing is known about the
      role of PPAR-gamma in antibody-induced demyelination in the absence of T-cell
      interactions and monocyte/macrophage activation. Therefore, we investigated PPAR
      gamma's involvement by using an in vitro model of inflammatory demyelination in
      three-dimensional aggregating rat brain cell cultures. We found that PPAR-gamma
      was not constitutively expressed in these cultures but was strongly up-regulated
      following demyelination mediated by antibodies directed against myelin
      oligodendrocyte glycoprotein (MOG) in the presence of complement. Pioglitazone, a
      selective PPAR-gamma agonist, partially protected aggregates from anti-MOG
      demyelination. Heat shock responses and the expression of the proinflammatory
      cytokine tumor necrosis factor-alpha were diminished by pioglitazone treatment.
      Therefore, pioglitazone protection seems to be linked to an inhibition of glial
      cell proinflammatory activities following anti-MOG induced demyelination. We show
      that PPAR-gamma agonists act not only on T cells but also on antibody-mediated
      demyelination. This may represent a significant benefit in treating multiple
      sclerosis patients.

PMID- 12503088
TI  - Transcriptionally mediated gene targeting of gas1 to glioma cells elicits growth
      arrest and apoptosis.
AB  - Induction of growth arrest-specific genes (gas1) prevents cell proliferation
      and/or leads to apoptosis in different cell types. In neurons, it has been
      recently reported that mild excitotoxic neuronal death is associated with gas1
      induction, and that overexpression of Gas1 induces apoptosis in terminally
      differentiated neurons or in proliferating neuroblastoma cells. In the present
      study, we have analysed the effects of the transcriptionally mediated targeting
      of gas1 to C6 rat glioma cells. Expression of Gas1 decreased glial proliferation
      and induced C6 cell apoptosis. While the identity of the caspase(s) responsible
      for Gas1-induced apoptosis in neurons has remained elusive, in C6 glioma cells,
      overexpression of Gas1 reproducibly activated caspase-3. Our results support the
      concept of targeted expression of gas1 as a potentially useful gene therapy
      strategy in the treatment of human gliomas.

PMID- 12503089
TI  - Impairment of protein homeostasis and decline of proteasome activity in
      microglial cells from adult Wistar rats.
AB  - Common symptoms of different neurodegenerative diseases start to develop in the
      second half of the human life. Several of these diseases, including Alzheimer's
      and Parkinson's disease, are accompanied by severe disturbances of protein
      metabolism and homeostasis in the brain. Because microglial cells are, to some
      extent, responsible for the maintenance of this homeostasis, age-related
      functional changes of the microglia are important. We established, therefore, the
      preparation of cultures of primary microglial cells isolated from adult animals
      in comparison to the widely used standard model, primary microglial cells
      isolated from newborn animals. In addition, we investigated changes in the
      activation and in the protein homeostasis within these cells. The protein
      turnover seems to be significantly impaired in microglial cells isolated from
      adult animals and this seems to be accompanied by a decline in proteasomal
      function, but not in the protease content. We were also able to demonstrate
      higher cell surface molecule expression and a higher basal NO release of
      microglia isolated from adult animals in comparison to the microglia isolated
      from newborn rats; however, the PMA stimulated oxidative burst was abolished
      completely in cells from adult animals. Microglia from adult animals were also
      not able to upregulate their protein metabolism after activation. From these
      investigations it was concluded that microglial cells from adult animals have
      significantly different metabolic properties in comparison to the widely used
      microglial cells from newborn animals.

PMID- 12503090
TI  - Neural progenitor cells resist excitatory amino acid-induced neurotoxicity.
AB  - The applications of neural progenitor cells in clinical therapy for neural
      degeneration, such as Parkinson's disease, Huntington's disease, and cerebral
      infarction, have long been explored widely. It had been suggested that these
      cells may block the apoptosis of ischemia-induced neuronal damage and may
      themselves resist neurotoxic factors. In the present study, neural progenitor
      cells derived from the cortex of rodent embryos were cultured with the mitogenic
      agent epidermal growth factor. It was observed that these progenitor cells could
      self-renew and differentiate into a number of types of neurons and glial cells.
      By using sodium nitroprusside, glutamate, and N-methyl-D-aspartate, these neural
      progenitor cells were shown to have a higher resistance to neurotoxicity induced
      by these drugs compared with primary neuronal cells. However, the release of
      nitric oxide in response to glutamate by these neural progenitor cells was
      similar to the released by primary neuronal cells. Also, when the glutamate
      stimulated increase in intracellular free Ca(2+) concentration was measured,
      stimulation of the glutamate receptors could not induce a significant influx of
      Ca(2+) into these progenitor cells until they differentiated. Our results suggest
      that the resistance of neural progenitor cells to neurotoxicity may be partially
      due to a lack of response to glutamate. In addition, some progenitor-generated
      neurotrophic factors may contribute to the resistance of these cells to nitric
      oxide-induced neurotoxicity.

PMID- 12503091
TI  - Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer's
      disease fibroblasts.
AB  - The regulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been
      implicated both in age-related neurodegenerative disease and in apoptosis.
      Previous in vitro studies suggest an interaction between GAPDH and the beta
      amyloid precursor protein (beta-APP), a protein directly involved in Alzheimer's
      disease (AD). New studies indicate that GAPDH is a multidimensional protein with
      diverse membrane, cytoplasmic, and nuclear functions; each is distinct from its
      role in glycolysis. The nuclear functions of GAPDH include a role in apoptosis
      that requires its translocation to the nucleus. Accordingly, beta-APP-GAPDH
      interactions, altering GAPDH structure in vivo, may affect energy generation,
      inducing hypometabolism, a characteristic AD phenotype. Because GAPDH is a
      multifunctional protein, pleiotropic effects may also occur in a variety of
      fundamental cellular pathways in AD cells. This may include unique GAPDH-RNA
      interactions. We report here the identification of a high-molecular-weight (HMW)
      GAPDH species present exclusively in the postnuclear fraction of AD cells. The
      latter is characterized by reduced GAPDH activity. The HMW GAPDH species was not
      detected in postnuclear age-matched control (AMC) fractions nor in AD whole-cell
      preparations. Each is characterized by normal GAPDH activity. By definition, the
      preparation of whole-cell extracts entails the destruction of subcellular
      structure. The latter findings indicate that the dissociation of the GAPDH
      protein from the HMW species restores its enzymatic activity. Thus, these results
      reveal a new, unique intracellular phenotype in AD cells. The functional
      consequences of subcellular alteration in GAPDH structure in AD cells are
      considered.

PMID- 12503092
TI  - Complete Freund's adjuvant immunization prolongs survival in experimental prion
      disease in mice.
AB  - We recently reported that immunization of mice with certain self-prion protein
      peptides induced specific T-cell and B-cell immune responses; importantly, this
      immunization was associated with a decrease in the number of protease-resistant
      PrP(Sc) particles recoverable in a transplanted, scrapie-infected syngeneic
      tumor. The present study was carried out to determine whether immunization with
      the immunogenic PrP peptides might influence the natural history of experimental
      scrapie in mice. We immunized C57BL/6 mice with self-prion peptides in complete
      Freund's adjuvant (CFA) or with CFA alone as a control and then infected the mice
      with mouse-adapted scrapie by injection either intraperitoneally or
      intracerebrally. We report here that immunization with CFA, irrespective of
      whether prion peptides were present in the inoculum, resulted in marked
      prolongation of survival of the mice, whether the challenge was intracerebral or
      intraperitoneal. Mice in the immunized and control groups that died contained
      equivalent amounts of PrP(Sc). Thus, CFA immunization has a therapeutic effect in
      experimental scrapie in mice, possibly by reducing the rate of PrP(Sc)
      accumulation in the brain.

PMID- 12503093
TI  - Loss of lipopolysaccharide-induced nitric oxide production and inducible nitric
      oxide synthase expression in scrapie-infected N2a cells.
AB  - In scrapie-infected cells, the conversion of the cellular prion protein to the
      pathogenic prion has been shown to occur in lipid rafts, which are suggested to
      function as signal transduction platforms. Neuronal cells may respond to
      bacterial lipopolysaccharide (LPS) treatment with a sustained and elevated nitric
      oxide (NO) release. Because prions and the major LPS receptor CD14 are
      colocalized in lipid rafts, the LPS-induced NO production in scrapie-infected
      neuroblastoma cells was studied. This study shows that LPS induces a dose- and
      time-dependent increase in NO release in the murine neuroblastoma cell line N2a,
      with a 50-fold increase in NO production at 1 microg/ml LPS after 96 hr, as
      measured by nitrite in the medium. This massive NO release was not caused by
      activation of the neuronal NO synthase (nNOS), but by increased expression of the
      inducible NOS (iNOS) mRNA and protein. However, in scrapie-infected N2a cells
      (ScN2a), the LPS-induced NO production was completely abolished. The absence of
      LPS-induced NO production in ScN2a was due not to abolished enzymatic activity of
      iNOS but to a complete inhibition of the LPS-induced iNOS gene expression as
      measured by Western blot and RT-PCR. These results indicate that scrapie
      infection inhibits the LPS-mediated signal transduction upstream of the
      transcriptional step in the signaling cascade and may reflect the important
      molecular and cellular changes induced by scrapie infection.

PMID- 12503094
TI  - Peripheral axotomy affects nicotinamide adenine dinucleotide phosphate diaphorase
      and nitric oxide synthases in the spinal cord of the rabbit.
AB  - Using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)
      histochemistry and nitric oxide synthase (NOS) immunocytochemistry combined with
      radioassay of calcium-dependent NOS activity, we examined the occurrence of
      NADPHd staining and NOS immunoreactivity (NOS-IR) in the dorsal root ganglia
      (DRG) neurons, dorsal root afferents, and axons projecting via gracile fascicle
      to gracile nucleus 14 days after unilateral sciatic nerve transection in the
      rabbit. Mild to moderate NADPHd staining and NOS-IR appeared in a large number of
      small and medium-sized to large neurons in the ipsilateral L4-L6 DRG, accompanied
      by enhanced NOS-IR of thick myelinated fibers in the ipsilateral L4-L6 dorsal
      roots. A noticeable increase in the density of punctate NADPHd staining occurred
      throughout laminae I-IV in the ipsilateral medial part of the dorsal horn in L4
      L6 segments. Concurrently, a statistically significant decrease in the number of
      small NADPHd-exhibiting neurons in laminae I-II and, in contrast to this, a
      statistically significant increase of medium-sized to large NADPHd-stained somata
      in the ipsilateral laminae III-VI of L4-L6 segments were found. A detailed
      compartmentalization of L4-L6 segments into gray and white matter regions
      disclosed substantially increased catalytic NOS activity and inducible NOS mRNA
      levels in the dorsal horn and dorsal column ipsilaterally to the peripheral
      injury. A noticeable increase in the number of thick myelinated NADPHd-exhibiting
      and NOS-IR axons was noted in the ipsilateral gracile fascicle, terminating in
      dense, punctate NADPHd staining in the neuropil of the gracile nucleus. These
      observations indicate that the de novo-synthesized NOS in the lesioned primary
      afferent neurons resulting after sciatic nerve transection may be involved in an
      increase in NADPHd staining and NOS-IR in the ipsilateral dorsal roots and dorsal
      horn of L4-L6 segments, whence NOS could be supplied to ascending axons of the
      gracile fascicle.

PMID- 12503095
TI  - Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia.
AB  - Ocular (uveoretinal) colobomas occur in one in 10,000 individuals and present a
      substantive cause of congenital poor vision. The genetic bases of most forms of
      uveoretinal coloboma are elusive; mutations in PAX2 are found in only a few cases
      of coloboma of the retina and optic nerve that occur with renal anomalies as part
      of the renal-coloboma syndrome (MIM#120330; #167409). From experimental data that
      upstream expression of sonic hedgehog (SHH) controls Pax2 expression in mice and
      zebrafish, and from clinical experience that colobomas are observed frequently in
      patients with holoprosencephaly, we hypothesized that SHH could be a candidate
      for non-syndromic ocular colobomas (NSOC). We identified a three-generation
      family in which both a proband and his mother presented with iris and uveoretinal
      colobomas without optic nerve involvement. A novel 24 bp deletion in the gene SHH
      was identified in these affected family members, and cosegregated with the
      phenotype. This is the first report of the association of SHH mutations and
      uveoretinal coloboma.

PMID- 12503096
TI  - What do ratings of cancer-specific distress mean among women at high risk of
      breast and ovarian cancer?
AB  - Women recruited from a hereditary cancer registry provided ratings of distress
      associated with different aspects of high-risk status and genetic testing and
      completed measures of general psychological distress, emotional and social
      health, and role functioning. Overall, high-risk status was rated as more
      distressing than undergoing genetic testing. Women without a personal history of
      cancer rated the level of distress associated with a positive test result to be
      greater than that associated with high-risk status. In contrast, level of
      distress associated with a positive test result was not significantly different
      from that associated with high-risk status for women with a personal history of
      cancer. Furthermore, women with a personal cancer history also anticipated that
      if they had an altered gene associated with increased risk of cancer, it would be
      less distressing than their diagnosis of cancer had been. Women with the highest
      ratings of cancer-related stress were less inclined to obtain testing, but were
      not more generally distressed or maladjusted. The need to interpret psychological
      distress and the stressfulness of genetic testing among high-risk women with
      respect to relevant comparison data is discussed.

PMID- 12503097
TI  - Thermodynamic determination of beta-hexosaminidase isoenzymes in mononuclear and
      polymorphonuclear leukocyte populations.
AB  - Isoenzymes of beta-hexosaminidase (Hex) were determined in mononuclear (MN) and
      polymorphonuclear (PMN) leukocytes, with a thermodynamic method using the
      chromogenic substrate sodio-3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-beta-D
      glucosaminide. Imprecision was very satisfactory, and the results are very much
      in agreement with those obtained using the fluorogenic substrates 4
      methylumbelliferyl N-acetyl-beta-D-glucosaminide and 4-methylumbelliferyl N
      acetyl-beta-D-glucosaminide 6-sulfate. In 163 healthy individuals we found, for
      the proportion as a percentage of the Hex A isoenzyme, significantly higher
      values (P < 0.001) in PMN than in MN cells (71.56 +/- 0.30% vs. 54.28 +/- 0.24%),
      meaning that it would not appear advisable to use total leukocyte lysates for
      evaluating this variable. The method is fast, precise, and highly suitable for
      the biochemical diagnosis and heterozygote screening of GM2 gangliosidoses, and
      would be applicable in cases of thermolabile Hex B and for detecting the B1
      variant.

PMID- 12503098
TI  - Prevalence of mitral valve prolapse in Stickler syndrome.
AB  - The prevalence of mitral valve prolapse in Stickler syndrome has been reported to
      be much higher than in the general population. As a result, it has been
      recommended that all patients with Stickler syndrome undergo routine
      echocardiography and have antibiotic prophylaxis prior to surgery. The purpose of
      this study was to evaluate the prevalence of mitral valve prolapse in a large
      cohort of UK patients with Stickler syndrome in whom the clinical diagnosis has
      been confirmed by molecular genetic analysis. Probands and pedigrees were
      identified from the Vitreoretinal Service database according to previously
      published criteria. Ophthalmic, skeletal, audiometric, and orofacial features
      were assessed. Affected individuals underwent a full cardiological examination
      including auscultation and two-dimensional echocardiography. Mutation analysis of
      the COL2A1 and COL11A1 genes was carried out. Seventy-eight patients from 25
      pedigrees were studied. Mutation analysis confirmed the clinical diagnosis in
      every pedigree. No patient was found to have clinical evidence of cardiovascular
      disease and no patient had significant mitral or other valvular prolapse on
      echocardiography. These data from a large cohort of UK patients with proven
      Stickler syndrome do not suggest an increased incidence of mitral valve prolapse
      over and above that found in the general population. Routine echocardiography
      screening and use of preoperative antibiotics are unnecessary and should be
      reserved for those individual cases where there is clear clinical indication.

PMID- 12503099
TI  - Biochemical characterization of two (C300F, P425T) arylsulfatase a missense
      mutations.
AB  - Metachromatic leukodystrophy (OMIM 250100) is a lysosomal storage disease caused
      by the deficiency of arylsulfatase A (ARSA, EC 3.1.6.8). This disease affects
      mainly the nervous system, because patients cannot degrade 3-O-sulfo
      galactosylceramide (sulfatide), a major myelin lipid. Here we describe the
      characterization of the biochemical effects of two arylsulfatase A missense
      mutations, P425T and C300F. Transfection experiments demonstrate the expression
      of residual ARSA enzyme activity for P425T, but not for C300F substituted ARSA.
      Relative specific activity determination showed that the P425T substituted enzyme
      has retained about 12% of specific enzyme activity, whereas the C300F substituted
      enzyme is reduced to less than 1%. Pulse-chase experiments reveal that both
      mutant proteins are unstable, with a half life of less than 6 hr. Increased
      secretion upon addition of NH(4)Cl indicates that the mutant proteins can pass
      the Golgi apparatus and thus are not degraded in the endoplasmic reticulum (ER),
      but in the lysosomes. This is supported by experiments, which demonstrate the
      presence of mannose-6-phosphate residues on the oligosaccharide side chains of
      the mutant proteins. Addition of the cysteine protease inhibitor leupeptin
      increases the amount of ARSA activity in cells expressing the P425T substituted
      enzyme, whereas no increase in activity was seen with C300F substituted ARSA.

PMID- 12503100
TI  - Lack of association between eNOS gene polymorphisms and ischemic heart disease in
      the Spanish population.
AB  - Through the nitric oxide (NO) production in the vascular system, the endothelial
      nitric oxide synthase (eNOS or NOS3) is a key enzyme in blood pressure regulation
      and atherosclerosis control. Several previous studies have suggested an important
      role of eNOS as a genetic risk factor for cardiovascular diseases. In this
      context, a genetic association study was carried out between two eNOS
      polymorphisms (the ecNOS4a/b VNTR and the G894T substitution) in a sample of 101
      nuclear families having one affected offspring of ischemic heart disease (IHD).
      Transmission disequilibrium test (TDT) revealed partial associations between the
      VNTR marker and IHD in patients with a type A behavior pattern (TABP) (P =
      0.0325, RR = 3.67) and for the haplotype formed by variant b of the VNTR and the
      T mutation of the G894T substitution in the IHD-affected subgroup having body
      mass index (BMI) lower than 25 (P = 0.0348, RR = 0.22). However, once multiple
      testing correction was applied, the associations became nonsignificant. A
      significant effect of the haplotype b-G increasing high-density lipoprotein
      cholesterol (HDL-C) plasma levels was detected (P = 0.021 after Bonferroni
      correction). From a population point of view, frequencies found for G894T
      substitution in Spain were significantly different from other populations.

PMID- 12503101
TI  - Molecular, biochemical, and phenotypic analysis of a hemizygous male with a
      severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome
      and a mutation in EBP.
AB  - X-linked dominant Conradi-Hunermann-Happle syndrome (CDPX2; MIM 302960) is a rare
      chondrodysplasia punctata primarily affecting females. CDPX2 is presumed lethal
      in males, although a few affected males have been reported. CDPX2 is a
      cholesterol biosynthetic disorder due to 3-beta-hydroxysteroid-delta8,delta7
      isomerase deficiency caused by mutations in the emopamil binding protein (EBP)
      gene. A 2.5-year-old Caucasian male was followed from the age of 6 weeks and
      noted to have significant developmental delay, hypotonia, seizures, and patchy
      hypopigmentation. Multiple congenital anomalies included a unilateral cataract,
      esotropia, crossed renal ectopia, stenotic ear canals, and failure to thrive,
      requiring G-tube placement. Multiple minor anomalies and ptosis were noted. No
      skeletal asymmetry or chondrodysplasia punctata were noted on skeletal survey at
      6 weeks and 13 months. An extensive genetic work-up including cholesterol (126
      176 mg/dl) and 7-dehydrocholesterol was unrevealing. However, the levels of 8(9)
      cholestenol and 8-dehydrocholesterol were mildly increased in plasma, which was
      confirmed in cultured fibroblasts. This prompted molecular analysis of the EBP
      gene, which revealed a novel hemizygous (nonmosaic) mutation in exon 2 (L18P).
      Two restriction digests were developed that confirmed this mutation in skin
      fibroblasts, blood, and buccal cells (all nonmosaic). We determined that the
      patient's mother (adopted) also has the L18P mutation enabling prenatal diagnosis
      of a normal male fetus. She has normal stature, no asymmetry, no cataracts at
      this time, and has a patch of hyperpigmentation on her chest best visualized on
      Woods lamp examination, characteristic of CDPX2. The mild maternal phenotype has
      been described previously. However, this nonmosaic missense mutation has resulted
      in a severe phenotype in her surviving son.

PMID- 12503102
TI  - X-linked dominant chondrodysplasia punctata (CDPX2) caused by single gene
      mosaicism in a male.
AB  - X-linked dominant chondrodysplasia punctata (CDPX2; Happle syndrome) is
      recognized almost exclusively in females, who display mosaic and asymmetric
      features, presumed to arise secondary to random X-inactivation. CDPX2 results
      from mutation of an X-linked gene coding for sterol-delta(8)-delta(7) isomerase
      (emopamil binding protein). We describe a boy with clinical features of CDPX2
      (including those presumed to arise usually secondary to functional mosaicism in
      females). Biochemical and molecular studies demonstrate that he is mosaic for a
      sterol-delta(8)-delta(7) isomerase gene mutation. He is the first reported
      example of single gene mosaicism giving rise to CDPX2 in a male.

PMID- 12503104
TI  - A clinical perspective of cystic fibrosis and new genetic findings: relationship
      of CFTR mutations to genotype-phenotype manifestations.
AB  - The present report describes several aspects of the relationship of mutations in
      the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene to
      phenotype expression of the disease including several clinical vignettes from the
      authors' experience. The genotype-phenotype relationships in CF are complex, and
      are affected by many factors, including pollution, smoking, bacterial infection,
      malnutrition, and certain therapeutic agents. The number of CFTR mutations is
      growing continuously and rapidly, and more than 1,000 mutations have been
      discovered so far. From a genetic point of view, the deltaF508 mutation is not
      only the most frequently encountered but also the most severe genetic lesion for
      homozygotes. The great clinical variability observed in patients with CF,
      particularly the severity of lung disease, involvement of the pancreas, and male
      infertility, are beginning to be better understood through the knowledge,
      although incomplete, of CFTR mutations and their phenotype expressions. This
      knowledge has had very significant research and clinical applications in all
      dimensions of the CF problem. It has not only contributed to the enhancement of
      better diagnosis and clinical management, but it also has opened new and
      unanticipated lines of investigation and research.

PMID- 12503105
TI  - Interrupted aortic arch in a child with trisomy 5q31.1q35.1 due to a maternal
      (20;5) balanced insertion.
AB  - Complex congenital heart defects (CHD) are associated with a variety of single
      gene abnormalities and chromosomal rearrangements. Of the various forms of CHD,
      aortic arch interruption, a conotruncal heart defect, is relatively uncommon.
      Here we report a male neonate with aortic arch interruption type B, secundum
      atrial septal defect, perimembranous ventricular septal defect, patent ductus
      arteriosus, aortic and subaortic stenosis, and trisomy 5q31.1q35.1 resulting from
      a maternal balanced insertion (20;5). Chromosomal deletions, including deletion
      22q11, have been reported with interrupted aortic arch (IAA); however, to our
      knowledge this is the first report of a trisomy of distal chromosome 5q
      associated with aortic arch interruption. Here we compare this child's features
      to other cases of trisomy 5q31.1q35.1, and review other causes of IAA. We
      conclude that gene dosage in this chromosomal region likely influences aortic
      arch development.

PMID- 12503106
TI  - Clinical and genetic heterogeneity in frontometaphyseal dysplasia: severe
      progressive scoliosis in two families.
AB  - Frontometaphyseal dysplasia is a rare genetic syndrome affecting the skeletal
      system and connective tissue. It is believed to be inherited as an X-linked
      trait. Features of frontometaphyseal dysplasia overlap with other skeletal
      dysplasias. Prominent supraorbital ridges, radiologic evidence of cranial
      hyperostosis, and flared metaphyses are characteristic. Scoliosis, a rare
      associated finding, is usually mild, and familial progressive scoliosis has not
      been reported so far. The skeletal dysplasia and the associated clinical findings
      show significant intra- and interfamilial variability. The syndrome has been
      suggested to be an allelic variant of the Melnick-Needles osteodysplasty, an X
      linked (dominant) entity. We present two families with frontometaphyseal
      dysplasia, in which both males and females showed the facial and skeletal
      features of the syndrome in association with progressive scoliosis. Some of the
      affected members also had hearing loss and urogenital anomalies, supporting the
      existence of the recently suggested entity "fronto-otopalatodigital
      osteodysplasty syndome".

PMID- 12503107
TI  - Hypertrichosis terminalis, gingival hyperplasia, and a characteristic face: a new
      distinct entity.
AB  - Congenital generalized hypertrichosis terminalis has been described in
      association with other features as gingival hyperplasia, osteochondrodysplasia,
      and a dysmorphic face. Bondeson and Miles [1993: Am J Med Genet 47:198-212]
      described a woman with universal congenital hypertrichosis terminalis associated
      with gingival hyperplasia; the face of this patient was coarse and different from
      other forms of hypertrichosis described before. We present an 11-year, 6-month
      old girl with universal congenital hypertrichosis terminalis, gingival
      hyperplasia, and a characteristic coarse face resembling the patient described by
      Bondeson and Miles [1993: Am J Med Genet 47:198-212]. We propose that this type
      of congenital generalized hypertrichosis terminalis, associated with gingival
      hyperplasia and a coarse face, is a distinctive new entity.

PMID- 12503108
TI  - Two new cases of analphoid marker chromosomes.
AB  - Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA represent
      a rare and interesting class of rearranged marker chromosomes. These SMCs are
      predicted to have a neocentromere and have been referred to as neocentric marker
      chromosomes (NMCs). We report the molecular cytogenetic characterization of two
      new cases of neocentromere-containing chromosomes, one on 1q43-44 and one on
      15q26. Both cases were examined using fluorescence in situ hybridization (FISH)
      with various alpha-satellite DNA probes, and no alphoid DNA was detected. In case
      1, the NMC originated from the distal long arm of chromosome 1 by chromosomal
      microdissection and reverse painting. This marker lacked detectable chromosome 1q
      subtelomeric sequences, and therefore appeared to be a small ring chromosome.
      After genetic counseling with a high risk for a MCA/MR syndrome (trisomy 1q43 -->
      q44), the family continued the pregnancy. At age 6 months, the infant
      demonstrated no congenital or developmental anomalies. This is the first
      published example of a NMC derived from chromosome 1q. The marker may be one of
      the smallest, if not the smallest, human NMC reported to date. In case 2, fetal
      ultrasonography indicated a complex heart defect (abnormal return of lower vena
      cava, atrial septum malformation) and bilateral hydronephrosis. Molecular
      cytogenetic analysis showed an inverted duplication of the distal long arm of
      chromosome 15 (tetrasomy 15q24 --> qter). The pregnancy was terminated. Autopsy
      demonstrated polycystic left kidney and dysplastic right kidney. Case 2
      represents the ninth report of a neocentromere on distal chromosome 15q,
      suggesting that this region may possibly especially support the formation of
      neocentromeres.

PMID- 12503109
TI  - Muellerian aplasia associated with ring chromosome 8p12q12 mosaicism.
AB  - We report on a woman with Muellerian aplasia, renal and skeletal anomalies, and
      minor dysmorphic signs. Conventional cytogenetic analysis revealed mosaicism for
      a small supernumerary, undefinable ring chromosome. Chromosome microdissection
      and reverse painting demonstrated that this marker contained pericentric material
      from chromosome 8 (8p12q12). Thus, we identified a Muellerian aplasia phenotype
      with partial trisomy 8 mosaicism.

PMID- 12503110
TI  - Atypical progeroid syndrome: an unknown helicase gene defect?
AB  - We describe a boy with chromosomal breakage syndrome, who died of hepatocellular
      carcinoma at the age of 17 years. Other findings included growth retardation,
      bilateral cataracts, premature graying of hair and elevated levels of urinary
      hyaluronic acid. Intellectual functions were normal. Although some manifestations
      were suggestive of Werner syndrome, the diagnosis could not be confirmed by
      molecular investigations. Therefore, this patient probably represents a
      provisionally unique syndrome, perhaps due to a mutation in a related (helicase)
      gene.

PMID- 12503111
TI  - True hermaphroditism with ambiguous genitalia due to a complicated mosaic
      karyotype: clinical features, cytogenetic findings, and literature review.
AB  - Abnormal recombination between the X and Y chromosomes during meiosis, occurring
      outside the pseudoautosomal region, can result in translocation of the SRY gene
      from the Y to the X chromosome, and consequently in abnormal sexual
      differentiation, such as the development of 46,XX males or true hermaphroditism.
      In this report we present clinical, cytogenetic, and molecular-cytogenetic data
      of a patient with ambiguous genitalia and true hermaphroditism, who had a unique
      mosaic karyotype, comprising three different cell lines: 46,XX(SRY+), 45,X(SRY+),
      and 45,X. The mosaic karyotype of our patient probably represents two different
      events: abnormal recombination between the X and Y chromosomes during paternal
      meiosis, and postzygotic loss of one of the X chromosomes. Replication studies
      demonstrated that in 80% of the XX cells, the SRY sequence was located on the
      active X chromosome. This finding suggests nonrandom X inactivation and, together
      with the presence of the SRY gene, explains the male phenotype of our patient. On
      the other hand, the presence of the 45,X cell line may have contributed to
      genital ambiguity. We conclude that fluorescence in situ hybridization (FISH)
      analysis with SRY probes is highly recommended and allows accurate diagnosis and
      optimal management in cases of 46,XX hermaphroditism and ambiguous genitalia.

PMID- 12503112
TI  - Distinctive spondylometaphyseal dysplasia in two siblings.

PMID- 12503113
TI  - Endogenous hydrogen sulfide overproduction in Down syndrome.

PMID- 12503114
TI  - Hereditary gingival fibromatosis (HGF) with hypertrichosis is unlinked to the
      HGF1 and HGF2 loci.

PMID- 12503116
TI  - Status of the human malformation map: 2002.

PMID- 12503117
TI  - Molecular etiology of gut malformations and diseases.
AB  - This review describes recent advances using animal models in the analysis of the
      molecular controls of gastrointestinal development, with specific attention to
      mutations causing maldevelopment similar to those seen in human gut
      malformations. By focusing on specific human gut pathologic conditions and
      maldevelopment, we describe the probable roles of signaling pathways, including
      the hedgehog pathway, the bone morphogenic protein pathway, and the role of the
      homeotic genes.

PMID- 12503118
TI  - Limb anomalies: Developmental and evolutionary aspects.
AB  - In this review we describe the developmental mechanisms involved in the making of
      a limb, by focusing on the nature and types of interactions of the molecules that
      play a part in the regulation of limb patterning and characterizing clinical
      conditions that are known to result from the abnormal function of these
      molecules. The latter subject is divided into sections dealing with syndromal and
      nonsyndromal deficiencies, polydactylies, and brachydactylies. Conditions caused
      by mutations in homeobox genes and fibroblast growth factors and their receptor
      genes are listed separately. Since the process of limb development has been
      conserved for more than 300 millions years, with all the necessary adaptive
      modifications occurring throughout evolution, we also take into consideration the
      evolutionary aspects of limb development in terms of genetic repertoire,
      molecular pathways, and morphogenetic events.

PMID- 12503119
TI  - Malformations of the craniofacial region: evolutionary, embryonic, genetic, and
      clinical perspectives.
AB  - Malformations of the craniofacial region are reviewed with respect to
      evolutionary, embryonic, genetic, and clinical perspectives under the following
      headings: How Old Is Our Head?, Head Organization Genes, Genetics of Craniofacial
      Anomalies, Craniofacial Derivatives, Anencephaly, Cephalocele, Holoprosencephaly,
      Craniosynostosis, Hypertelorism, Branchial Arch Anomalies, and Orofacial
      Clefting.

PMID- 12503120
TI  - Defects of blastogenesis.
AB  - Ever more frequent and closer involvement by clinical geneticists and counselors
      in the prenatal assessment of development mandates a better understanding of all
      stages of human ontogeny, but especially those of earliest development during
      which most of the lethal and all of the gross, multiple and complex defects of
      morphogenesis arise. Because of the phenomenon of universality, i.e., identical
      molecular inductive mechanisms involved in the process of embryonic pattern
      formation in all vertebrates, experimental animals indeed are a most valuable
      approach to an understanding of the causal and formal aspects of development and
      are beginning to forge essential, strong bonds between molecular biologists and
      clinicians in a mutually supportive discipline of developmental biology. However,
      to grieving parents of a stillborn fetus with, say, Pentalogy of Cantrell,
      sirenomelia or otocephaly, mouse data offer little comfort or reassurance about
      recurrence; thus, it is imperative to make ever more effective a science of human
      teratology (sensu lato) with participating reproductive geneticists,
      obstetricians, neonatologists, ultrasonographers, pediatric/fetal pathologists,
      cytogeneticists and pediatric geneticists to generate the diagnostic,
      pathogenetic and causal data necessary to counsel and to comfort the parents. Few
      molecular data exist on causes of blastogenetic defects in humans; however, the
      phenomenon of parsimony, whereby the same "morphogenetic" molecule, say, sonic
      hedgehog (SHH), is "deployed" simultaneously or sequentially during the
      morphogenesis (and even the histogenesis) of several/many embryonic primordia,
      makes it likely that a genetic/epigenetic disturbance of such an inductive system
      will have multiple effects on blastogenetic, organogenetic and perhaps also
      histogenetic events in the embryo. If causally defined, such a pattern of
      anomalies constitutes pleiotropy, and the embryo/fetus can be said to have a
      syndrome. If cause is unknown, the presumption of pleiotropy is less certain, and
      the fetus/infant may be said to have an "association" with low empiric recurrence
      risk.

PMID- 12503121
TI  - Ionic liquids: solvents for the electrodeposition of metals and semiconductors.
AB  - In a wider sense, ionic liquids are molten salts that melt below 100 degrees C.
      As their name suggests, they are solely composed of ions and many combinations of
      organic and/or inorganic cations and anions exist. Depending on the systems they
      can reach electrochemical windows of more than 4 V and thus they give access to a
      number of elements that cannot be electrodeposited from aqueous solutions, such
      as the light and refractory metals, as well as elemental and compound
      semiconductors. Presumably, ionic liquids will become important for
      electrochemical nanotechnology.

PMID- 12503122
TI  - Advances in battery technology: rechargeable magnesium batteries and novel
      negative-electrode materials for lithium ion batteries.

PMID- 12503123
TI  - Influence of structural variations in 1-alkyl(aralkyl)-3-methylimidazolium
      hexafluorophosphates and bis(trifluoromethyl-sulfonyl)imides on physical
      properties of the ionic liquids.
AB  - A series of twenty four 1-alkyl(aralkyl)-3-methylimidazolium hexafluorophosphates
      and bis(trifluoromethyl-sulfonyl)imides are prepared and the influence of
      structural variations in the imidazolium cation and the identity of the anion on
      physical properties (phase transition, density, viscosity, and surface tension)
      of the ionic liquids is determined.

PMID- 12503124
TI  - Density functional studies of the ground- and excited-state potential-energy
      curves of stilbene cis-trans isomerization.
AB  - Using spin-unrestricted density functional theory (the VWN Becke-Perdew
      potential), including broken-symmetry and spin-projection methods, we have
      obtained the potential-energy curves as a function of the central torsional angle
      of stilbene in the ground (S0), the first excited triplet (T1), the first excited
      singlet (S1), and the doubly excited singlet (S2) states. The thermal trans-->cis
      isomerization of stilbene passes through a diradical broken-symmetry electronic
      structure around the twisted conformation (90 degrees central torsional angle) in
      the ground state. Our calculations support the proposed triplet mechanism for
      sensitized cis [symbol: see text] trans photoisomerization and the nonadiabatic
      singlet mechanism proposed by Orlandi and Siebrand. On the T1 potential-energy
      curve, the rotation of the C=C bond for both trans- and cis-stilbene will lead
      stilbene to the twisted conformation, from which the twisted stilbene will decay
      to the ground-state surface that is nearly isoenergetic with the T1 surface and
      has diradical electronic structure in the twisted region. On the S1 potential
      energy curve, the energy increases in the direction from trans- to the twisted
      stilbene, and crosses with the neutral doubly excited S2 potential-energy curve,
      which has a minimum at the twisted structure and is lower in energy than the
      zwitterionic doubly excited state. The twisted stilbene around the energy minimum
      of the neutral doubly excited S2-state will decay onto the ground-state surface
      from where the rotation of the C=C bond leads the twisted stilbene to either the
      trans or cis configuration and the isomerization of stilbene is then completed.
      Similar studies have also been performed on a stilbene derivative with a
      substituent group, NHCOCH3.

PMID- 12503125
TI  - Molecules for materials: structures, thermochemistry, and electron affinities of
      the digermanium fluorides Ge2Fn/Ge2Fn- (n = 1-6): a wealth of unusual structures.
AB  - A systematic investigation of Ge2Fn/Ge2Fn- systems was carried out with five
      density functional theory (DFT) methods in conjunction with DZP++ basis sets. For
      each compound various structures, including minima, transition states and other
      energetically low lying stationary points, were optimized. The geometries and
      relative energies are discussed and compared. Adiabatic electron affinities,
      vertical electron affinities and anion vertical detachment energies are reported.
      Three types of dissociation energies pertaining to the global minima for each
      compound are reported. The theoretical predictions are in good agreement with the
      limited available experimental results. Many unusual structural features are
      predicted for these systems. Neutral Ge2F is predicted to have a bridged C2v
      structure, while its anion is very floppy, with the bridged structure very
      slightly favoured. The Ge2F2 molecule is predicted to have the butterfly
      structure known from experiment for Si2H2, while the Ge2F3- ion has a trans-bent
      structure. Ge2F3 is predicted to have an unprecedented FGe-F-GeF structure with
      no Ge-Ge bond, while its anion has a somewhat more conventional monobridged
      structure, analogous to that of the nonclassical vinyl cation. Neutral Ge2F4 has
      a dibridged structure of C2h symmetry, while its anion has a trans-bent structure
      with a very long Ge-Ge bond. The Ge2F5 molecule is doubly bridged and has no Ge
      Ge bond, while the anion is of the type F2Ge-F-GeF2, again with no Ge-Ge bond.
      Ge2F6 has the anticipated ethane structure, as does its anion, but with a very
      long Ge-Ge bond. The adiabatic electron affinities (EAad) are predicted to be
      2.12 (Ge2F), 2.03 (Ge2F2), 2.02 (Ge2F3), 1.64 (Ge2F4), 4.57 (Ge2F5), and 2.66 eV
      (Ge2F6), respectively, by the BHLYP method, which is regarded as the best method
      in the present paper for predicting EAs. Comparisons with the analogous C2Fn and
      Si2Fn systems reveals some interesting trends and differences. For example, while
      C2F6 will not capture an electron, Si2F6 is predicted to have small electron
      affinity (0.73 eV), while that of Ge2F6 is substantial. The same trend to larger
      EAs on going down the Periodic Table is seen for the X2F5 systems, with 1.77
      (C2F5), 2.68 (Si2F5), and 4.57 eV (Ge2F5). However, the EAs do not follow a
      monotonic trend for the X2F, X2F3 and X2F4 systems with respect to the series X =
      C, Si, Ge.

PMID- 12503126
TI  - Evidence of pronounced electronic coupling in a directly bonded fullerene-
      ferrocene dyad.
AB  - A new donor-acceptor dyad (7) involving a ferrocene moiety as donor and an
      azafullerene as acceptor has been synthesized by treating bisazafullerenyl (1)
      with ferrocenium hexafluorophosphate. This compound represents the first example
      of a fullerene-based dyad where two electroactive groups are connected by only a
      single sigma-bond. The cyclic voltammetry of 7, in comparison to the
      corresponding reference systems, clearly reveals strong electronic coupling
      between the ferrocene and the azafullerene moiety in the ground state. For
      example, the Fc-based, reversible, one electron oxidation wave is significantly
      positively shifted by 183 mV with respect to that of the parent ferrocene. This
      indicates the existence of intramolecular charge transfer (ICT) from the donating
      Fc to the accepting azafullerenyl group. Photophysical studies on 7 were carried
      out by means of emission and transient absorption spectroscopy. An instantaneous
      deactivation of the fullerene singlet excited-state results in the formation of
      the charge-separated (C59N.-)-(Fc.+) radical pair. From the charge-transfer
      dynamics with a lower limit of > or = 5 x 10(10) s-1, we infer strong electronic
      coupling (V) between the azafullerene and the ferrocene moiety of the order of 60
      cm-1 in benzonitrile.

PMID- 12503127
TI  - Structural isomers of C20 revisited: the cage and bowl are almost isoenergetic.

PMID- 12503128
TI  - Surface structure of untreated parallel and fishbone carbon nanofibres: an
      infrared study.

PMID- 12503129
TI  - Atmospheric formation of OH radicals and H2O2 from alkene ozonolysis under humid
      conditions.

PMID- 12503130
TI  - Water activity in aqueous solutions of homogeneous electrolytes: the effect of
      ions on the structure of water.

PMID- 12503131
TI  - Ionomer-coated electrodes and nanoelectrode ensembles as electrochemical
      environmental sensors: recent advances and prospects.
AB  - This Minireview focuses on recent advances in the use of ionomer-coated
      electrodes and nanoelectrode ensembles for the determination of redox ions at
      trace concentration level with special stress on applications for environmental
      monitoring. After an overview on the most recent developments of ionomer-coated
      electrodes, attention is directed towards their use for speciation analysis in
      environmental samples. In particular, some examples such as the selective
      determination of inorganic and metallorganic species of different toxicity and
      the redox state speciation of multiply charged ions are discussed. The second
      part of the Minireview deals with the development and electroanalytical use of a
      new kind of nanostructured electrode, named nanoelectrode ensembles, which are
      prepared by template synthesis within the pores of microporous guest membranes.
      Advantages, peculiarities, and limits of such devices are discussed together with
      perspectives for their use in electroanalytical sensing at trace and ultratrace
      concentration levels in environmental samples.

PMID- 12503132
TI  - Distance measurements in the nanometer range by pulse EPR.
AB  - Distances of 1.5 to 8 nm in macromolecules and supramolecular assemblies can be
      measured by pulse electron paramagnetic resonance (EPR) experiments. In
      conjunction with site-directed spin labeling or the use of paramagnetic tracers
      this opens up a new method for the structure determination of complex systems
      such as biomacromolecules or nanostructured polymer materials. The extent of
      information obtained from such measurements crucially depends on the proper
      choice of the pulse sequence, on optimization of temperature, concentration, and
      matrix and on the procedure used for data analysis.

PMID- 12503133
TI  - 13C NMR lineshapes for the 13C2H2H' isotopomeric spin grouping.
AB  - Carbon-13 NMR lineshape calculations applicable for deuterated methylene spin
      groupings are described. The interplay between anisotropic interaction strengths,
      isotropic couplings, and dynamic parameters are considered in this investigation.
      It is shown that 13C lineshapes for this system are informative and provide
      details on numerous factors that are difficult to ascertain by alternative means.
      It is demonstrated that in the vicinity of the deuteron T1 minimum, quadrupole
      quadrupole cross-correlation revealed through the 13C lineshape, may provide a
      useful methodology for the study of molecular reorientational anisotropy in
      condensed phases. Similarly, quadrupole--dipolar interferences induce significant
      second order frequency shifts that provide dynamic information not accessible by
      means of conventional spin relaxation experiments.

PMID- 12503134
TI  - Application of artificial neural networks to combinatorial catalysis: modeling
      and predicting ODHE catalysts.
AB  - This paper shows how artificial neural networks are useful for modeling catalytic
      data from combinatorial catalysis and for predicting new potential catalyst
      compositions for the oxidative dehydrogenation of ethane (ODHE). The training and
      testing sets of data used for the neural network studies were obtained by means
      of a combinatorial approach search, which employs an evolutionary optimization
      strategy. Input and output variables of the neural network include the molar
      composition of thirteen different elements presented in the catalyst and five
      catalytic performances (C2H6 and O2 conversion, C2H4 yield, and C2H4, CO2, and CO
      selectivity). The fitting results indicate that neural networks can be useful in
      high-dimensional data management within combinatorial catalysis search
      procedures, since neural networks allow the ab initio evaluation of the
      reactivity of multicomponent catalysts.

PMID- 12503135
TI  - Molecular dynamics study of the calcium ion transfer across the
      water/nitrobenzene interface.
AB  - A study on the calcium ion transfer across the water/nitrobenzene interface is
      presented. The potential of mean force was calculated and a good agreement was
      found between the experimental and the calculated free energy of transfer. This
      is a monotonically increasing function of the distance to the interface, and the
      process was found to be non-activated. The evolution of the first and second
      hydration shells was analysed as a function of the distance to the interface; the
      first hydration shell remains intact whereas the second hydration shell suffers a
      severe water loss. Water finger formation was also found, with behaviour similar
      to that already described for other ions in different interfaces. As far as we
      know, a direct comparison between the calculated number of water molecules
      dragged with an ion into the organic phase and the experimental results is
      presented for the first time and a very good agreement was found.

PMID- 12503136
TI  - An upper bound on the theoretical activity coefficient of non-electrolytes.
AB  - An upper bound on the activity coefficient, calculated from its theoretical
      definition, is formulated and discussed in detail for binary solutions of non
      electrolytes. It is compared with a previous order-of-magnitude analysis that
      predicted it to be e. The existence of an upper bound points to a major
      discrepancy between theoretical and actual (experimentally measured) activity
      coefficients in highly nonideal solutions: The actual activity coefficient may be
      much higher than the theoretical upper bound. It is shown that the theoretical
      activity coefficient of the more volatile component must indeed be much smaller
      than e for slightly soluble components. For the less volatile component, the
      upper bound on the theoretical activity coefficient is shown to be approximately
      equal to the relative volatility. However, it is demonstrated that this upper
      bound may be grossly exaggerated when the relative volatility is high. In
      addition, as shown for aqueous solutions of n-alkanes that are less volatile than
      water, even when the upper bound is much higher than e, it may still be much
      smaller than the actual activity coefficient.

PMID- 12503137
TI  - Photoelectron spectra and electronic structure of some diastereomeric
      quinuclidine derivatives.
AB  - The molecular and electronic structure of three pairs of diastereomeric
      quinuclidine derivatives (1-6) have been investigated by quantum chemical
      calculations and UV photoelectron (PE) spectroscopy. Compounds 1-6 each possess a
      hydroxymethyl group at C2 and an ethyl (1, 2), vinyl (3, 4) or ethynyl group (5,
      6) at C5. The diastereomeric pairs differ only in the configuration of carbon C2
      to which the hydroxymethyl group is attached. The 1-azabicyclo[2.2.2]octane cages
      of 1-6 are slightly twisted. The torsion angles show opposite signs in the
      pseudoenantiomeric pairs and vary only little with the degree of unsaturation in
      the C5 substituent. In all compounds the hydroxymethyl group forms an
      intramolecular hydrogen bond with the nitrogen atom of the bicycle in the gas
      phase (in contrast to the crystalline and liquid state). The PE spectra of the
      diastereomers are nearly identical. Compared to unsubstituted quinuclidine, the
      orbital of the nitrogen lone pair electrons n(N) is stabilized by 0.3-0.4 eV,
      which is a result of partially compensating contributions of the OH...N hydrogen
      bond and substituent effects. Among these a substantial through-bond interaction
      of the n(N) with a pi(CC) orbital is detected for 3-6. The marked differences of
      the properties of 1-6 in the gas phase versus solid state and solution are
      emphasised. In solution the ethynyl azabicyclics 5 and 6 are more polar than the
      vinyl analogues 3 and 4.

PMID- 12503138
TI  - The CH3CH2N: diradical: generation conditions and determination of its ionization
      energies.

PMID- 12503139
TI  - Unusual two-dimensional multicomponent self-assembly probed by scanning tunneling
      microscopy.

PMID- 12503140
TI  - Two-photon absorption spectra of pyrylium derivatives.

PMID- 12503141
TI  - Surface functionalization of H-terminated silicon surfaces with alcohols using
      lodoform as an in situ iodinating agent.

PMID- 12503142
TI  - A novel ionization path of nitric oxide: resonance, not perturbation, plays a
      role.

PMID- 12503143
TI  - Conductance calculations for real systems on the nanoscale.
AB  - Electron transport across molecular junctions is a rapidly growing topic at the
      borderline between physics and chemistry. We review calculations which were done
      in the Landauer transport formalism for monovalent systems, ranging from clusters
      to fullerenes. A realistic description of molecular conductance can be achieved
      by a density functional based approach to the calculation of the electronic
      transport properties.

PMID- 12503144
TI  - Terahertz biosensing technology: frontiers and progress.

PMID- 12503145
TI  - Effects of the dendrimer cage on O2 binding of dendritic cobalt(II) porphyrins.
AB  - Two types of dendritically functionalized cobalt(II) porphyrins were prepared and
      investigated in the presence of 1,2-dimethylimidazole, pyridine, and 1
      methylimidazole. Continuous-wave (CW) and pulse electron paramagnetic resonance
      (EPR) and electron nuclear double resonance (ENDOR) techniques revealed specific
      information on the oxygenated forms of these porphyrins. The ENDOR and hyperfine
      sublevel correlation (HYSCORE) spectra showed that in [1.CoII.1,2.DiMelm]-O2,
      with secondary amide moieties in the dendritic branching, no hydrogen bond forms
      between the bound O2 and a dendritic amide NH moiety. This hydrogen bond had
      earlier been proposed on basis of the large dioxygen affinity of the
      corresponding FeII complex. For both [1.CoII.1,2-DiMelm]-O2 and the ester
      derivative [2.CoII.1,2-DiMelm]-O2, which lacks H-donor centers in the periphery
      of the porphyrin, ENDOR experiments clearly showed that the dendritic branches
      are closely packed in toluene. The analysis of the g values, the cobalt hyperfine
      interactions, and the hyperfine and nuclear quadrupole couplings of the directly
      coordinated nitrogen of the axial base showed an increased ionicity in the cobalt
      dioxygen bond for [1.CoII.1,2-DiMelm]-O2. This observation is linked to the
      packing and the polarity of the dendritic branches and can be related to the O2
      and CO affinity of the corresponding FeII complexes.

PMID- 12503146
TI  - Reversible bulk photorelease of strontium ion from a crown ether-linked
      merocyanine.
AB  - The use of a crown-ether-linked merocyanine, DCM-crown, for producing
      photoinduced, long-lived and reversible concentration jumps of metal cations is
      reexamined. In this new investigation, the excited-state behavior of DCM-crown
      complexed with a strontium ion in acetonitrile is found to exhibit the same
      trends as those previously reported with calcium and lithium ions. However, some
      new features provide evidence for cation photorelease to the bulk. Subpicosecond
      transient absorption experiments confirm the initial fast photodisruption of the
      interaction between the ion and the crown, and the formation of a loose complex
      after intramolecular charge transfer within the chromophore. Two additional steps
      are observed. Firstly, a continuous red shift of the gain spectrum is seen on the
      subnanosecond scale. It is assigned to the movement of the Sr2+ cation away from
      the chromophore, partly to the bulk of the solvent and partly towards the
      formation of an ultraloose complex with oxygen atoms of the crown. Secondly, a
      free-ligand-like absorption remains after the complete decay of the excited
      state. This band, which signals a total photorelease of the Sr2+ ion, disappears
      with a characteristic time of about 110 ns, attributed to the recomplexation of
      the crown in the ground state of the dye.

PMID- 12503147
TI  - Ab-initio study of NMR chemical shifts of water under normal and supercritical
      conditions.
AB  - We present a theoretical investigation of the hydrogen nuclear magnetic resonance
      (NMR) chemical shift and the magnetic susceptibility of normal and supercritical
      water using a recently developed ab initio approach in the framework of density
      functional perturbation theory. The results are in very good agreement with
      experiment. The shifts can be used to determine whether the atomic
      configurations, taken from a first principles simulation, give a good description
      of the system on a microscopic scale. In particular, the hydrogen chemical shifts
      are very sensitive to the character of the hydrogen bond network, which plays a
      crucial role in the macroscopic properties of liquid water under normal and
      supercritical conditions.

PMID- 12503148
TI  - The light emission observed from small palladium particles during passage of
      electronic current.
AB  - Light emission spectra were measured from separate Pd particles excited by the
      passage of electrical current through them. As the particle size decreases or
      input power increases the intensities of peaks increase more strongly in the high
      energy part of the spectra than in the low-energy part. Moreover, new peaks can
      appear in the high-energy region. The color of an emission center changes from
      red to blue upon an increase in electric power fed into the Pd particle. This
      process is reversible and can be observed visually. On a further increase in
      feeding power, the Pd particle can be brought to a premolten state and can even
      melt. The integral intensity of light emission then increases dramatically, and
      the light emission spectrum changes and corresponds to thermal radiation. This
      latter process is irreversible.

PMID- 12503149
TI  - Selective catalytic reduction of NO by NH3 on Cu-faujasite catalysts: an
      experimental and quantum chemical approach.
AB  - The selective catalytic reduction (SCR) of NO by NH3 in the presence of O2 on Cu
      faujasite (Cu-FAU) has been studied. Substitution of some Cu2+ with H+ and Na+
      cations, compensating for the negative charge of the zeolite framework, forms the
      various CuHNa-FAU studied. The amount of Cu was held constant and the proportion
      of H+ and Na+ varied in the sample. The substitution of Na+ for H+ increases
      sharply the SCR rate by lowering the temperature of reaction by about 150 K. It
      is proposed that the rate increase mainly comes from an unhindered migration of
      Cu from hidden to active sites and a modification of the redox properties of Cu
      species. The former was demonstrated by diffuse reflectance IR spectroscopy of
      adsorbed CO. The change in redox properties was demonstrated by a faster
      oxidation of Cu+ to Cu2+ (rate-determining step). Quantum chemical calculations
      on model clusters of CuHNa-FAU indicate that the faster rate of oxidation can be
      explained by a higher lability of protons in the absence of Na, which can be then
      removed from the catalyst more easily to yield H2O during the oxidation process.

PMID- 12503150
TI  - In situ polymerisation of pyrrole in nanochannels produced by means of AFM
      lithography.

PMID- 12503151
TI  - Anionic versus neutral protonation--an ab initio analysis with a triadic formula.

PMID- 12503152
TI  - Determination of the density distribution of interface states from high- and low
      frequency capacitance characteristics of the tin/organic pyronine-B/p-type
      silicon structure.

PMID- 12503153
TI  - Exciton and excimer formation in DNA at room temperature.

PMID- 12503154
TI  - Continuously variable hole injection in organic light emitting diodes.

PMID- 12503155
TI  - Femtochemistry and femtobiology: the new age.

PMID- 12503156
TI  - Nonempirical quantification of molecular interactions in supramolecular
      assemblies.
AB  - A new nonempirical scheme for the computation of realistic atomic charges from
      the sole knowledge of molecular or crystalline structures and of two ab initio
      parameters per chemical element (a configuration energy and the radius of the
      most diffuse valence orbital) is presented. Charge distributions obtained from
      this formalism are consistent with common chemical knowledge and found to be in
      agreement with available X-ray diffraction studies. They are also compatible with
      electrical-field gradients derived from solid-state NMR measurements. It is also
      shown how the total electrostatic energy associated with each charge distribution
      may be used to quantify van der Waals as well as hydrogen bond interactions from
      an energetic point of view. Finally, the position of the new formalism relative
      to other ab initio schemes is discussed both qualitatively and quantitatively.

PMID- 12503157
TI  - Liposomes possess drastic capabilities for topological transformation.
AB  - Morphological and topological changes of biological membranes play essential
      roles in cellular activities. It has been thought that these transformations are
      made possible through interactions with proteins. However, direct observation of
      giant liposomes by optical dark-field microscopy reveals that the lipid bilayer
      itself possesses the ability to undergo topological transformation.

PMID- 12503158
TI  - Oxophlorin and metallooxophlorin radicals--DFT studies.
AB  - A flexible oxophlorin macrocycle, which allows the location of labile hydrogen
      atoms alternatively at the pyrrole nitrogen, oxygen, or meso-carbon atoms, has
      been studied by density functional theory (DFT). DFT calculations were carried
      out on oxophlorin 1, 5-hydroxyporphyrin 2, and two isomers of oxophlorin 3 and 4
      (the proton added at the tetrahedral C(15) or the C(10) meso-carbon,
      respectively). The oxophlorin-hydroxyporphyrin structural changes are
      appropriately reflected by the significant changes of the meso carbon-oxygen bond
      lengths, which are in the limits of typical C=O and C-O distances. The
      rearrangement that creates the iso-oxophlorin macrocycle 3 (4) results in near
      tetrahedral geometry around the C(15) (C(10)) carbon atom, with the C(14)-C(15)
      and C(15)-C(16) (C(9)-C(10) and C(10)-C(11)) bond lengths corresponding to a
      single C-C bond. 5-Hydroxyporphyrin 2 is aromatic and has a bond pattern
      resembling that of regular porphyrin. In 1, 3, and 4, a localization of single
      and double bonds was seen, which agrees with the nonaromatic nature of
      oxophlorin, or isooxophlorin. The relative stability decreases in the order: 2
      (0) > 3 (4.85) > 1 (5.11) > 4 (10.04) > 3-cis (12.89) (the number in parentheses
      is the relative energy, in kcal mol-1). The energy difference between the NH-cis
      and NH-trans tautomers, which is 8.04 kcal mol-1 for 3, results from a
      destabilizing NH-NH cis-interaction. DFT calculations were performed on the
      oxophlorin dianion radical (OP.)2- and a series of metallooxophlorin radicals
      ([(OP.)LiI]-, [(OP.)ZnII], [(OP.)GaIII]+, and (OP.)GaIIIF, in order to assess
      their electronic structures. Typically, the largest atomic spin density was found
      at the C(10) (C(20)) and C(15) meso positions, with the spin density at C(15)
      being twice as large as that at C(10). The spin density at the C(5) atom is
      negligible. A large spin density was found at the O(5) oxygen atom. The amount of
      spin density at the meso positions decreased as the cationic charge increased.
      When considering the absolute values of the spin densities, the opposite trend
      was observed at the pyrrolic carbon atoms. The spin density at the nucleus (Fermi
      contact terms) has also been analyzed. The spin distributions of iron oxophlorins
      determined by NMR were attributed to an oxophlorin radical electronic structure.
      The calculated spin density maps accounted for the essential NMR spectroscopic
      features of important intermediates in the heme degradation process--iron
      oxophlorin complexes. The DFT calculations reproduced the following spectroscopic
      patterns: a) |delta H(15)|>|delta H(10)|>>|delta (beta-H)|, b) a sign alteration
      of the contact shifts for identical substituents located on the same pyrrole
      ring.

PMID- 12503159
TI  - Energetics of the ligated vanadium dications VO2+, VOH2+, and [V,O,H2]2+.
AB  - Charge-stripping mass spectrometry and electronic structure calculations are
      combined to examine the energetics of the vanadium-containing dications VO2+,
      VOH2+, [HVOH]2+, and [V(OH2)]2+. Energy-resolved measurements, in conjunction
      with quantum-mechanical calculations, led to ionization energies (IE) of (VO+) =
      16.6 +/- 0.3 eV and IE(VOH+) = 16.0 +/- 0.4 eV. Born-Haber cycles reveal that
      VO2+ and VOH2+ are both thermochemically stable dications with respect to their
      charge-separation asymptotes. Depending on the mode of ion generation, the
      [V,O,H2]+ monocations are formed as variable mixtures of the structural isomers
      [HVOH]+ and [V(OH2)]+. The measured IE([V,O,H2]+) = 13.7 +/- 0.3 eV is between
      the theoretical predictions for these isomers, indicating that mixtures of both
      isomers are sampled in the experiments. According to the theoretical results,
      [V(OH2)]2+ is also a thermochemically stable dication, whereas [HVOH]2+ is
      suggested to be metastable.

PMID- 12503160
TI  - Effect of competitive complex formation on patterning and front propagation in
      periodic precipitation.
AB  - The Co(OH)2 Liesegang pattern (from Co2+ and NH4OH) propagates in space by
      periodic band formation at the head due to precipitation and band disappearance
      at the tail due to dissolution in excess NH4OH. Introduction of Ni2+, which
      competes with Co2+ for complex formation with ammonia, into the system led to
      several interesting observations: slower propagation, fewer bands, and increased
      spacing between them. Above a cutoff concentration of Ni2+ (0.13 M for [Co2+]0 =
      0.100 M), only a uniform precipitation zone was observed. The quantity delta X =
      |XNi-Xfree|, namely, the difference in the position of last band in the system
      with nickel relative to that without nickel attained at a fixed time (93 h), was
      found to oscillate as the initial concentration of NH4OH ([NH4OH]0) was varied.
      It was shown that variations in the concentration of intermediate NH4+ act as
      precursors for these oscillations: [NH4+] was measured with an ammonia-specific
      electrode, and the difference delta [NH4+] = |[NH4+]Ni-[NH4+]free| at 93 h
      exhibited oscillations with [NH4OH]0 similar to those obtained in delta X.
      Theoretical calculations based on the model of Muller and Polezhaev agreed with
      the experimental results.

PMID- 12503161
TI  - Experimental and theoretical evidence of C-H...O hydrogen bonding in liquid 4
      fluorobenzaldehyde.
AB  - The presence of C-H...O hydrogen bonds in liquid 4-fluorobenzaldehyde has been
      studied by a combination of theoretical and spectroscopic methods. Ab initio
      calculations yielded bond energies and preferred bonding geometries, and the
      calculated spectroscopic properties have been compared with the experimental
      results. The presence of C-H...O hydrogen bonds in the liquid phase is strongly
      supported by vibrational and NMR spectroscopic data. Particular attention is paid
      to the spectroscopic effects related to the predicted shortening of the C-H bond
      engaged in the C-H...O contact. The concentration-dependent intensity in the C-H
      stretching region is tentatively assigned to a blue-shift effect due to C-H...O
      hydrogen bonding.

PMID- 12503162
TI  - Thermodynamics of hydrogen bond patterns in supramolecular assemblies of water
      molecules.
AB  - The PACHA (Partial Atomic Charges and Hardnesses Analysis) formalism is applied
      to various supramolecular assemblies of water molecules. After a detailed study
      of all available crystal structures for ice polymorphs, we shown that the
      hydrogen bond strength is roughly constant below 1 GPa and considerably weakened
      above that value. New hydrogen bond patterns are proposed for ice IV, V, and VI
      after (EB) (electrostatic balance) minimization. For other polymorphs, there is
      an almost perfect coincidence between experimental and predicted hydrogen bond
      patterns. The evolution of hydrogen bond energy as a function of molecular
      geometry in water clusters with up to 280 water molecules and in large
      supramolecular compounds is quantitatively described. Intermolecular hydrogen
      bonds are found to lie between -9 and -32 kJ mol-1, the stronger interaction
      occurs within the spherical fully disordered water droplet buried at the heart of
      Muller's superfullerene keplerate. The weakest one occurs in a chiral molecular
      snub cube built from six calix[4]resorcinarene and eight water molecules.
      Intramolecular hydrogen bonds are found in the range -10-100 kJ mol-1 and can
      thus be considerably stronger than intermolecular bonds. Finally, through the
      investigation of a clathrate type I compound, it was possible to obtain a deep
      insight of the host-guest interactions and self-assembly rules of water cages in
      these materials.

PMID- 12503163
TI  - Adsorption of 2,2'-dipyridyl disulfide on Au/Pt core/shell bimetallic clusters
      loaded on TiO2: fine control of adsorptivity for organosulfur compounds.

PMID- 12503164
TI  - NMR and conductivity study of polymer electrolytes in the imide family:
      P(EO)/Li[N(SO2CnF2n+1)(SO2CmF2m+1)].

PMID- 12503165
TI  - Calculations of the rate constants for the hydrogen abstraction reactions C2H3 +
      CH4-->C2H4 + CH3 and C2H3 + C2H6-->C2H4 + C2H5.

PMID- 12503166
TI  - Coherent anti-stokes Raman scattering (CARS) correlation spectroscopy.

PMID- 12503167
TI  - Observation of functional group mediated assembling of dendritic molecules by
      STM.

PMID- 12503168
TI  - Biological physics--origin and perspectives.
AB  - Biology and Physics share common ancestors. The two sciences have drifted apart
      during the last century, although they have often mutually fertilized each other.
      Often the discovery of a new physical method has triggered dramatic progresses in
      biology but there are also numerous examples of biology-inspired new developments
      in physics. In this special issue of ChemPhysChem, various facets and new
      developments of the interface between physics and biology are pointed out.

PMID- 12503169
TI  - The quantum physics of photosynthesis.
AB  - Biological cells contain nanoscale machineries that exhibit a unique combination
      of high efficiency, high adaptability to changing environmental conditions, and
      high reliability. Recent progress in obtaining atomically resolved structures
      provide an opportunity for an atomic-level explanation of the biological function
      of cellular machineries and the underlying physical mechanisms. A prime example
      in this regard is the apparatus with which purple bacteria harvest the light of
      the sun. Its highly symmetrical architecture and close interplay of biological
      functionality with quantum physical processes allow an illuminating demonstration
      of the fact that properties of living beings ultimately rely on and are
      determined by the laws of physics.

PMID- 12503170
TI  - Myoglobin, a paradigm in the study of protein dynamics.
AB  - More than 40 years have passed since Kendrew determined the structure of sperm
      whale myoglobin. It gave us the first insight into the impressive architecture of
      an alpha helical protein folded via loops into a well ordered, nearly spherical
      molecule. As time progressed, thousands of new protein structures were published
      with increasing resolution. The myoglobin structure was also continuously
      improved and, three years ago, a resolution of 0.9 A was achieved. A wide variety
      of spectroscopic techniques have been applied to study the dynamics of this
      molecule and the electronic properties of the heme iron atom. Even nowadays,
      experiments on myoglobin are still of great interest for a number of reasons:
      Physical research cannot go into all details in a large number of systems. In
      semiconductor physics, most concepts were developed by investigating germanium
      and silicon and were subsequently used to understand more complicated
      semiconductor systems; myoglobin plays a similar role in molecular biophysics.
      Concepts like "energy landscape", "conformational substates", "dynamic
      transition", or "protein-specific motions" should be of general relevance for
      understanding the physics of biological macromolecules. In biology, functionally
      important processes often occur at conditions and time scales where physical
      experiments are extremely difficult and yield ambiguous results. Going to low
      temperatures often allows one to separate the different dynamic processes.
      Another helpful tool is molecular engineering. Specific alterations in the
      sequence of the protein open the possibility to modify reaction rates and to
      retard the kinetics.

PMID- 12503171
TI  - Force spectroscopy of single biomolecules.
AB  - Many processes in the body are effected and regulated by highly specialized
      protein molecules: These molecules certainly deserve the name "biochemical
      nanomachines". Recent progress in single-molecule experiments and corresponding
      simulations with supercomputers enable us to watch these "nanomachines" at work,
      revealing a host of astounding mechanisms. Examples are the fine-tuned movements
      of the binding pocket of a receptor protein locking into its ligand molecule and
      the forced unfolding of titin, which acts as a molecular shock absorber to
      protect muscle cells. At present, we are not capable of designing such high
      precision machines, but we are beginning to understand their working principles
      and to simulate and predict their function.

PMID- 12503172
TI  - Cell adhesion as wetting transition?
AB  - Cell adhesion is controlled by a complex interplay of short range (lock-and-key)
      forces mediated by cell surface receptors, a phalanx of (short and long range)
      nonspecific (generic) interactions, and last but not least membrane elasticity.
      The physical basis of cell adhesion is explored by the design of simplified model
      systems, mimicking cell and tissue surfaces, enabling local measurements of
      cellular shape changes and adhesion forces by microinterferometry. Cell adhesion
      can be understood as first-order dewetting transition that results in the
      formation of adhesion plaques, such as focal adhesion sites of cells, which allow
      cell adhesion at astonishingly low receptor densities. The repeller molecules of
      the glycocalix play a key role for the control of the adhesion transition and the
      mechanical stability of the adhering cells by relaxing the strength of the
      binding forces. Stress fibers are postulated to be essential for the
      stabilization of adhesion domains against leverage through bending moments
      enforced by hydrodynamic shear forces.

PMID- 12503173
TI  - Physics in cell biology: on the physics of biopolymers and molecular motors.
AB  - "What is Life?" is the title of a book by Erwin Schrodinger, first published in
      1944. This book is a bold attempt to try to understand some of the wonders of
      life in terms of physics, in particular statistical mechanics. Since the
      publication of this visionary book, we have seen a revolution in molecular
      biology complemented by the development of new physical tools like single
      molecule spectroscopy. The goal of this article is to highlight some examples
      where physics can contribute to questions in cell biology. One might hope that
      through interdisciplinary research one can get closer to answering Schrodinger's
      fundamental question.

PMID- 12503174
TI  - Electrical interfacing of nerve cells and semiconductor chips.
AB  - The electrical interfacing of individual nerve cells and silicon microstructures
      is considered, as well as the assembly of elementary hybrid systems made of
      neuronal networks and semiconductor microelectronics. Without electrochemical
      processes, coupling of the electron-conducting semiconductor and the ion
      conducting neurons relies on a close contact of cell membrane and oxidised
      silicon with a high resistance of the junction and a high conductance of the
      attached membrane. Neuronal excitation can be elicited and recorded from the chip
      by capacitive contacts and by field-effect transistors with an open gate.
      Integrated iono-electronic system are obtained by the outgrowth of neuronal
      networks on the surface of the silicon chip, by implementing electrical circuits
      in the chip and by two-way interfacing of the neuronal and the electronic
      components.

PMID- 12503175
TI  - Stochastic resonance in biology. How noise can enhance detection of weak signals
      and help improve biological information processing.
AB  - Noise is usually thought of as the enemy of order rather than as a constructive
      influence. In nonlinear systems that possess some sort of threshold, random noise
      plays a beneficial role in enhancing the detection of weak information-carrying
      signals. This phenomenon, termed stochastic resonance, does find useful
      applications in physical, biological, and biomedical contexts. Certain biological
      systems may even use this effect for optimizing function and behavior.

PMID- 12503176
TI  - The map in your head: how does the brain represent the outside world?
AB  - In neurophysics, a "map" is a neuronal representation of the outside world. It
      originates from spatiotemporal activity of a sensory organ. For example, touch
      provides a one-to-one representation of our skin in the cortex, a somatosensory
      map. In a similar way, visual and auditory maps are representations of the retina
      and the cochlea and provide us with spatial, temporal, and, more generally,
      spatiotemporal maps of sensory activity. In this introduction we concentrate on
      temporal aspects and show how temporal maps arise in the brain. Through prey
      localization the sand scorpion, the barn owl, and the paddle fish provide
      fascinating examples of neuronal maps, which are analyzed in detail.

PMID- 12503177
TI  - Single virus tracing: visualization of the infection pathway of a virus into a
      living cell.

PMID- 12503178
TI  - A Fed for the church.

PMID- 12503179
TI  - Beware the hair soup.

PMID- 12503180
TI  - A quick HIV test.

PMID- 12503181
TI  - Mommy's home. More parents choose to quit work to raise their kids.

PMID- 12503182
TI  - Will it rid the church of clergy sex abuse this time?

PMID- 12503183
TI  - A message from the heart.

PMID- 12503184
TI  - Molecule of the moment.

PMID- 12503185
TI  - Roles of DNA repair methyltransferase in mutagenesis and carcinogenesis.
AB  - Alkylation of DNA at the O6-position of guanine is one of the most critical
      events leading to induction of mutation as well as cancer. An enzyme, O6
      methylguanine-DNA methyltransferase, is present in various organisms, from
      bacteria to human cells, and appears to be responsible for preventing the
      occurrence of such mutations. The enzyme transfers methyl groups from O6
      methylguanine and other methylated moieties of the DNA to its own molecule,
      thereby repairing DNA lesions in a single-step reaction. To elucidate the role of
      methyltransferase in preventing cancer, animal models with altered levels of
      enzyme activity were generated. Transgenic mice carrying extra copies of the
      foreign methyltransferase gene showed a decreased susceptibility to alkylating
      carcinogens, with regard to tumor formation. By means of gene targeting, mouse
      lines defective in both alleles of the methyltransferase gene were established.
      Administration of methylnitrosourea to these gene-targeted mice led to early
      death while normal mice treated in the same manner showed no untoward effects.
      Numerous tumors were formed in the gene-defective mice exposed to a low dose of
      methylnitrosourea, while none or only few tumors were induced in the
      methyltransferase-proficient mice. It seems apparent that the DNA repair
      methyltransferase plays an important role in lowering a risk of occurrence of
      cancer in organisms.

PMID- 12503186
TI  - Amelioration of prolidase deficiency in fibroblasts using adenovirus mediated
      gene transfer.
AB  - Prolidase deficiency is an autosomal recessive inherited disease characterized
      clinically by frequent infections, mental retardation, and various skin lesions.
      Fundamental treatments for these manifestations have not been established. We
      performed adenovirus-mediated gene transfer of human prolidase cDNA into
      fibroblasts from patients with prolidase deficiency. Infection with the
      adenovirus vector carrying human prolidase cDNA increased prolidase activity in
      fibroblasts up to approximately 7.5 times of that of normal control fibroblasts.
      This indicates the feasibility of adenovirus-mediated gene therapy to treat
      patients with prolidase deficiency in the future.

PMID- 12503187
TI  - Suppression of serum-induced c-jun expression by activated Ki-ras in human colon
      cancer cells.
AB  - Through gene-targeting, we have established human colon cancer cell lines, HK2-6
      and HKe-3, with and without activated Ki-ras, respectively, derived from a human
      colon cancer cell line HCT116, and we have reported that activated Ki-ras is
      involved in the deregulation of c-myc expression. To further examine the relation
      between Ki-ras-mediated signals and other immediate early genes, c-jun was
      analyzed on these cells stimulated by serum. Rapid and strong induction of c-jun
      was observed in HKe-3, but not in HCT116 or HK2-6. To elucidate the regulatory
      mechanisms of c-jun expression by Ki-ras, protein kinase C (PKC) and c-Raf were
      examined at serum-starved and serum-stimulated conditions. Phosphorylations of c
      Raf were same among these cells, however, the cytosolic PKC activity in HKe-3 was
      two times higher than that in HCT116 on serum-starved and serum-stimulated
      conditions. These results suggested that serum responsiveness of c-jun may be
      suppressed by activated Ki-ras through PKC rather than c-Raf pathway in colon
      cancer cells.

PMID- 12503188
TI  - A comprehensive method to scan for point mutations of the glucose 6 phosphate
      dehydrogenase gene.
AB  - We have developed a fast and comprehensive method to scan for point mutations in
      a gene on X chromosome. A target region of the gene is first amplified. Then,
      using the amplified product as a template, PCR is carried out with multiple short
      length forward primers arrayed in tandem in the scanned region, and a common
      reverse primer. The absence of amplified product defines the site of a mutation
      within a narrow region of the primer recognition site. To evaluate our method,
      point mutations in exon 12 of the human glucose-6-phosphate dehydrogenase (G6PD)
      gene were used as a model system. Out of 12 Singaporean G6PD-deficient patients,
      6 cases were shown by the method to have a nucleotide change in this exon.
      Sequence analysis confirmed the presence of a nucleotide change in the region
      identified by our scanning. Thus, our method is accurate in localizing mutations
      within a narrow region, and allows large numbers of samples to be handled
      simultaneously.

PMID- 12503189
TI  - A convenient method for genotyping of human O6-methylguanine-DNA
      methyltransferase polymorphism.
AB  - O6-methylguanine-DNA methyltransferase (MGMT) is one of the DNA repair enzymes in
      mammals. We previously screened the variant alleles for the MGMT gene in the
      general population, and found three variants (V1, V2, V3), two of which caused
      amino acid substitutions (Leu84Phe for V1, and Trp65Cys for V2). In order to
      accelerate the ecogenetic and pharmacogenetic studies on MGMT polymorphism, we
      therefore developed a new PCR-based RFLP method for genotyping. The present
      method has some advantages over the initial PCR-single strand conformation
      polymorphism (SSCP) method, particularly regarding its simplicity, rapidity and
      specificity.

PMID- 12503190
TI  - Dinucleotide repeat polymorphism in 65k-glutamate decarboxylase gene.

PMID- 12503191
TI  - Germline mutations of the APC gene in two Japanese adenomatous polyposis
      patients.
AB  - Germline mutations of the adenomatous polyposis coli (APC) gene have been
      reported in patients with familial adenomatous polyposis (FAP) and are believed
      to be an early event in colorectal carcinoma. We report the results of screening
      for germline mutations of the APC gene in 4 cases of 2 kindreds using non
      radioactive PCR-SSCP (polymerase chain reaction-single strand conformation
      polymorphism) analysis. The mutation in kindred 1 was a 4 bp deletion at codon
      849 in exon 15, resulting in a frameshift leading to truncation of the APC gene
      product. In kindred 2, a transversion of C to G at codon 2038 was observed,
      resulting in an amino acid change from leucine to valine. In this case, it is
      possible to screen presymptomatic diagnosis easily and quickly by digestion with
      restriction enzyme EcoNI.

PMID- 12503192
TI  - Mevalonic acidemia: first case of Japan.
AB  - Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase
      deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes.
      We report the first case of Japan. The clinical course is characterized by
      intrauterine growth retardation, postnatal growth failure, intractable diarrhea,
      liver dysfunctions and death at three months of age. Dysmorphic features
      including triangular face, protrusion of forehead, hypertelorism, low set ears
      and micrognathism were noted. High mevalonic acid level was found by GC/MS.

PMID- 12503193
TI  - A nager acrofacial dysostosis syndrome patient with severe respiratory distress
      syndrome (RDS).
AB  - Nager acrofacial dysostosis is characterized by radial defect and the facial
      manifestations like Treacher-Collins syndrome. There are few reports about this
      syndrome in Japan. We report a typical Japanese Nager syndrome patient. He was
      complicated with respiratory distress syndrome.

PMID- 12503194
TI  - An azoospermic male with an unbalanced autosomal-Y translocation.
AB  - An azoospermic male with an unbalanced translocation between the Y chromosome and
      chromosome 15 was examined in the present study. Testicular biopsy found only
      Sertoli cells only within the seminiferous tubules of the 35-year-old patient.
      Chromosome analysis, using the techniques of G and C banding and fluorescent in
      situ hybridization revealed an abnormal karyotype of
      46,XY,der(15)t(Y;15)(q12;p11). Deoxyribonucleic acid (DNA) analysis confirmed the
      presence of the genes such as DAZ and YRRM1 which are known to control
      spermatogenesis. The cause of spermatogenetic dysfunction in this particular
      patient therefore.

PMID- 12503195
TI  - The Cohen syndrome: report of a case.
AB  - We report on a sporadic case satisfied with a proposed diagnostic criteria for
      Cohen syndrome. This 10 year-old Japanese boy had truncal obesity, short stature,
      mild mental retardation, hypotonia, maxillary hypoplasia, micrognathia, narrow
      hands and feet, high-arched palate, prominent upper central incisors, high nasal
      bridge, but no pigmentary retinopathy. Autosomal recessive manner of inheritance
      was suggested by the pedigree.

PMID- 12503196
TI  - Megalocornea-mental retardation syndrome: an additional case report.
AB  - We report here on a Japanese male infant with megalocornea-mental retardation
      (MMR) syndrome. He had megalocornea (corneal diameter: 13 mm) without glaucoma,
      developmental retardation, hypotonia, frontal bossing, high-arched palate, carp
      like mouth, micrognathia, and delayed myelination. He seems to be included in
      Verloes type of the MMR syndrome.

PMID- 12503197
TI  - Cancer genome targets: RAF-ing up tumor cells to overcome oncogene addiction.

PMID- 12503198
TI  - New treatment option for postmenopausal women with early breast cancer.

PMID- 12503199
TI  - GSIs described as most important finding in cancer-targeting research.

PMID- 12503200
TI  - FDA grants orphan-drug status to Aeterna's Neovastat for kidney cancer.

PMID- 12503201
TI  - FDA approves extra safe chemotherapy drug.

PMID- 12503202
TI  - New cancer drug designed to overcome drug-resistant cells.

PMID- 12503203
TI  - Introgen obtains key patent obtained for p53-targeted chemotherapy.

PMID- 12503204
TI  - Cell fusion technology vaccine tested in kidney cancer clinical trial.

PMID- 12503205
TI  - Decitabine has promising clinical activity in chronic myeloid leukemia.

PMID- 12503206
TI  - deCODE generates first 3D image of anticancer drug activity.

PMID- 12503207
TI  - Cream to be tested as skin cancer care.

PMID- 12503208
TI  - Anastrozole (Arimidex) in clinical practice versus the old 'gold standard',
      tamoxifen.
AB  - For the past 25 years, the estrogen antagonist tamoxifen has been considered the
      'gold standard' for the treatment of breast cancer, despite certain tolerability
      issues and the risk of developing resistance. The aromatase inhibitors work by
      blocking the conversion of androgens to estrogen and were developed for use in
      patients where ovarian function had ceased (naturally, surgically or
      pharmacologically). Anastrozole, a third-generation nonsteroidal aromatase
      inhibitor that is a highly potent and selective inhibitor of the aromatase
      enzyme, has been shown to be superior to the gold standard tamoxifen for the
      first-line treatment of postmenopausal women with advanced breast cancer. As
      second-line therapy, anastrozole has shown superior survival compared with
      megestrol acetate and is also efficacious as neoadjuvant treatment in
      postmenopausal women and in combination with goserelin for the treatment of
      premenopausal women with advanced breast cancer. More recently, the results of
      the ATAC (anastrozole, tamoxifen, alone or in combination) trial, a large study
      in 9366 patients, demonstrated that anastrozole was significantly superior to
      tamoxifen for the treatment of postmenopausal women with early breast cancer,
      with regards to disease-free survival (p = 0.013) and incidence of contralateral
      breast cancer (p = 0.007). In addition, anastrozole was shown to be significantly
      better tolerated than tamoxifen with respect to endometrial cancer (p = 0.02),
      vaginal bleeding/discharge (p < 0.0001 for both), ischaemic cerebrovascular
      events (p = 0.0006), thromboembolic events (p = 0.0006) and hot flushes (p <
      0.0001), while tamoxifen was associated with significantly less musculoskeletal
      disorders and fractures than anastrozole (p < 0.0001 for both). This review
      focuses on both the clinical pharmacology and the clinical data of anastrozole
      with emphasis on its future applications.

PMID- 12503209
TI  - Gemtuzumab ozogamicin: promise and challenge in patients with acute myeloid
      leukemia.
AB  - CD33 is a suitable target to guide delivery of a toxic moiety to most acute
      myeloid leukemia cells. Gemtuzumab ozogamicin (Mylotarg) is a humanized antiCD33
      monoclonal antibody covalently linked to a derivative of a cytotoxic antibiotic,
      calicheamicin. As a single agent, gemtuzumab ozogamicin has activity (complete
      remission rate of 15-20%) in patients with relapsed disease. Gemtuzumab
      ozogamicin-based combinations are being studied as induction, maintenance and
      relapse regimens. The chemical hepatotoxicity often observed with gemtuzumab
      ozogamicin therapy is of little clinical consequence. However, hepatic veno
      occlusive disease is a relatively frequent and serious toxicity for which no
      clear risk factors, other than stem cell transplantation, have been defined.
      Gemtuzumab ozogamicin-based regimens may be particularly worthy of study in
      patients with acute promyelocytic leukemia. Gemtuzumab ozogamicin is approved as
      single-agent therapy for patients over the age of 60 years in first relapse who
      are not considered candidates for cytotoxic therapy. The administration of
      gemtuzumab ozogamicin should be carried out under a level of supervision
      commensurate with that afforded other intensely myelosuppressive agents.
      Gemtuzumab ozogamicin-based combinations should not be prescribed outside the
      research setting until further data is available.

PMID- 12503210
TI  - Organ preservation strategies in bladder cancer.
AB  - Bladder cancer is a significant cause of morbidity and mortality. Promising
      results with organ preservation strategies using multimodality treatment over the
      last decade offers an option for bladder preservation in a significant proportion
      of patients who currently undergo cystectomy. The primary goal of the bladder
      sparing approach remains optimal patient survival. A multidisciplinary approach
      involving urologists, radiation oncologists and medical oncologists will go a
      long way in improving the prognosis and quality of life of these patients.
      Progress in molecular characterization of bladder cancer and definition of new
      targeted therapies will provide new opportunities to tailor treatment to the
      specific needs of the individual. Introduction of chemoprevention strategies in
      patients with dysplasia and recurrent transitional cell cancer may reduce the
      rate of late cystectomies. This will further improve the efficacy of bladder
      preserving strategies. Improved techniques in delivery of radiation therapy will
      lead to more dose escalation with little toxicity and will allow the addition of
      further chemotherapeutic drugs or an increase in the dose or duration of
      concurrent chemotherapy. Most likely the next round of large trials will define
      the role of synchronous chemo radiotherapy once the results from Phase III
      studies comparing them with radiotherapy alone are published. The use of
      cytotoxic drugs such as gemcitabine and taxanes synchronous with radiation
      remains experimental today but may be incorporated into refined treatment
      protocols in coming years.

PMID- 12503211
TI  - Managing locally advanced bladder cancer.
AB  - Locally advanced bladder cancer comprising tumor stages pT3a, pT3b, pT4a of the
      1997 TNM system and/or involvement of regional lymph nodes can be cured by
      radical cystectomy. However, at least 50% of patients experience systemic
      progression within 5 years after surgery. In order to improve the fate of these
      patients, the administration of additional therapy has been studied in various
      forms, such as neoadjuvant and adjuvant systemic chemotherapy, as well as
      combined radiochemotherapy. Results from more than a dozen randomized Phase III
      trials on adjunctive chemotherapy, which include cystectomy as definite treatment
      have been reported. Whether neoadjuvant or adjuvant systemic chemotherapy is the
      superior form of adjunctive therapy for locally advanced bladder cancer continues
      to be a matter of dispute.

PMID- 12503212
TI  - Prognostic value of p53 overexpression in bladder tumors treated with Bacillus
      Calmette-Guerin.
AB  - Bacillus Calmette-Guerin intravesical therapy is the standard treatment of
      superficial bladder tumors at high risk of recurrence and progression to muscle
      invasion disease. To date, there is no well established predictive factor of
      response to Bacillus Calmette-Guerin intravesical therapy. The prognostic value
      of p53 overexpression in bladder tumors is controversial. Most investigators have
      found no correlation between p53 status assessed before Bacillus Calmette-Guerin
      intravesical therapy and patient outcome. On the other hand, it is acknowledged
      that the persistence of p53 overexpression after Bacillus Calmette-Guerin
      intravesical therapy is predictive of progression in patients treated for
      carcinoma in situ. Since conflicting data have been reported, further evaluation
      of the impact of p53 overexpression in patients treated with Bacillus Calmette
      Guerin intravesical therapy for bladder carcinoma is required.

PMID- 12503213
TI  - Advances in the staging of renal cell carcinoma.
AB  - Renal cell carcinoma is increasingly being diagnosed at an earlier stage owing to
      medical advances. Since the pathologic stage is the most crucial predictor of
      patient outcome, an accurate and universal tumor staging system is of utmost
      importance. The TNM staging system, after multiple revisions, has evolved into a
      more precise system that correlates with cancer specific survival. Renal cell
      carcinoma staging systems have important clinical implications pertaining to
      nephron sparing surgery and the need for adrenalectomy or lymphadenectomy.

PMID- 12503214
TI  - Multimodality treatment of metastatic renal cell carcinoma.
AB  - The treatment of choice for nondisseminated disease is surgery. However, the 5
      year survival rates for all stages do not exceed 60%, even in contemporary
      series. Further improvement will most likely have to await the development of a
      more effective systemic therapy and the application of combined treatment
      modalities to counter the relatively high number of patients presenting with
      advanced stages. Treatment options in metastatic disease include nephrectomy,
      sometimes in combination with metastasectomy in selected cases, alone or
      cytoreductive surgery followed by immunotherapy. Alternatively, one may initially
      apply immunotherapy and perform adjuvant nephrectomy in the case of a response,
      or proceed to immunotherapy as a monotherapy. Nevertheless, long-term survival
      ranges from merely 5 to 10% depending strongly on patient selection criteria.
      Concepts and progress in this field appear to be of major interest for modern uro
      oncologists following the advent of immunotherapeutic strategies that require a
      surgical intervention at some stage of the treatment cascade.

PMID- 12503215
TI  - Current concepts in the treatment of Ewing's sarcoma.
AB  - Current concepts in the treatment of patients with Ewing's sarcoma are presented
      focusing on the role of chemotherapy, radiation therapy and surgical resection.
      Particular attention is given to current methods of limb salvage. Problem areas,
      including the pelvis, proximal femur and spine, are discussed.

PMID- 12503216
TI  - Recent advances in the field of tubulin polymerization inhibitors.
AB  - In recent years, enormous progress has been made in the field of tubulin
      targeting agents. Several companies and academic laboratories have entered this
      field and competition has become very strong. Nevertheless, clinically promising
      compounds often face substantial limitations, such as high systemic toxicity,
      poor water solubility and bioavailability, as well as complex synthesis and
      isolation procedures. As a drawback of established drugs, like paclitaxel or the
      vinca alkaloids, the outcome of cancer chemotherapy is often affected by the
      emergence of the multidrug resistance phenotype. Among the recently disclosed
      tubulin polymerization inhibitors, there are several interesting low molecular
      weight compounds with improved oral bioavailability and demonstrated activity
      against multi-drug resistance positive phenotypes. As documented by the imidazole
      based combretastatin analogs, to name just one example, chemical optimization of
      a lead structure resulted in compounds with potent in vitro and in vivo activity
      along with appropriate pharmacodynamic and pharmacokinetic requirements for a
      potential therapeutic candidate. Currently, several compounds are undergoing
      Phase I or Phase II clinical trials, among them orally bioavailable sulfonamides
      or dolastatin 10. Several other compounds are close to entering Phase I trials.
      The purpose of this review is to focus on the most recent advances in tubulin
      polymerization inhibitors from a survey of the published patent literature and
      related publications between late 1999 and April 2002. However, biological data,
      especially for the inhibition of tubulin polymerization, obtained from different
      laboratories cannot easily be compared.

PMID- 12503217
TI  - Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy.
AB  - alpha-fetoprotein has long been considered the 'gold-standard' in the field of
      tumor markers. During the several decades since the recognition of mammalian
      alpha-fetoprotein as a tumor-associated fetal protein, it has been purified,
      characterized, cloned and sequenced for use in the clinical diagnostic
      laboratory. However, the biological role of alpha-fetoprotein in the regulation
      of cancer growth has received comparatively little attention. Only during the
      last decade has the modulatory role of alpha-fetoprotein in neoplastic growth
      been realized and implemented in experimental models. This review examines the
      basis for the current consensus that alpha-fetoprotein does indeed regulate
      neoplastic growth through the presence of an alpha-fetoprotein cell surface
      receptor that undergoes internalization to the cell interior. Studies involving
      uptake of this fetal protein have since culminated in radio imaging reports as
      well as the use of alpha-fetoprotein as an anticancer drug conjugate. Finally,
      the therapeutic utilization of alpha-fetoprotein and its peptidic fragments as
      growth-response modifiers encompasses biological events, such as apoptosis G
      coupled signal transduction, gene therapy, vaccination and cancer
      chemoprevention.

PMID- 12503218
TI  - Rethinking circumcision.

PMID- 12503219
TI  - Rethinking circumcision.

PMID- 12503220
TI  - HRT, HERS, NIH, WHI: alphabet soup?

PMID- 12503221
TI  - Prevention and Medicare: can an old insurance program be taught new tricks?

PMID- 12503222
TI  - Prevalence of cardiovascular risk factors in erectile dysfunction.
AB  - OBJECTIVE: Thirty million men in the United States may have erectile dysfunction,
      and coronary artery disease (CAD) is the major cause of death in men over 55
      years old. Several studies have shown a correlation between erectile dysfunction
      and risk factors for coronary artery disease. Hyperlipidemia plays a pivotal role
      in CAD, and obesity is now considered an independent risk factor for CAD.
      Therefore, we attempted to determine the prevalence of obesity and
      hyperlipidemia, along with other established risk factors such as diabetes,
      hypertension, and tobacco use, in men with erectile dysfunction. METHODS: Men who
      had had symptoms of erectile dysfunction for at least six months were recruited
      from the Center for Sexual Function. Participants underwent detailed clinical
      interviews, blood analyses, and physical examinations including calculation of
      body mass index, and they completed a questionnaire on sexual function. RESULTS:
      Of the 154 men evaluated, 44% had hypertension; 23% had diabetes mellitus; 16%
      used tobacco; 79% had a body mass index of > 26 kg/m2; and 74% had a low-density
      lipoprotein cholesterol level of > 120 mg/dL. CONCLUSION: Impotence is an
      important symptom, and its presence should instigate assessment and aggressive
      management of coexistent risk factors for CAD. Intervention could restore sexual
      function and ultimately improve cardiovascular health.

PMID- 12503223
TI  - Evidence for gender-specific associations between leptin and olfaction.
AB  - BACKGROUND: The adipocyte-derived hormone leptin regulates food intake by
      stimulation of the long leptin receptor isoform in the hypothalamus. The long
      leptin receptor is also expressed in the piriform cortex, an area involved in the
      relay of olfactory cues. In rodents, both olfaction and leptin influence food
      seeking. OBJECTIVE: To examine whether serum leptin levels are associated with
      olfaction in humans. SUBJECTS: Two distinct samples were analyzed. The population
      based sample, 60 men and 61 women, was randomly selected from a population living
      in Molndal, Sweden. The obese sample, 31 men and 27 women, was from the ongoing
      Swedish Obese Subjects (SOS) study. METHODS: Olfactory function was assessed with
      a two-part test used at Connecticut Chemosensory Clinical Research Center.
      RESULTS: In the population-based sample, multiple regression analysis revealed a
      gender difference (interaction gender x leptin; P = .016) between the association
      of odor identification and logarithmically transformed (log) leptin when
      adjusting for smoking and log body mass index (BMI). In men the association was
      positive (beta = 13.2; P = .0026), whereas in women it was negative (beta = 
      11.4; P = .050). When further adjusting for the influence of menopause and
      estrogen treatment, the negative association between odor identification and
      leptin became stronger for women in the population-based sample (beta = -13.7; P
      = .027). In the obese sample, the associations were similar in direction to those
      observed in the population-based sample, although nonsignificant. CONCLUSION:
      Serum leptin levels were associated with odor identification in a randomly
      selected population. The association was gender-specific and independent of BMI.
      High odor identification scores were associated with high serum leptin levels in
      men and low serum leptin levels in women. This provides further support for
      previously recognized gender differences in the leptin system and suggests
      alternative ways for leptin to modulate its effects.

PMID- 12503224
TI  - Diagnosis, prevention, and treatment of osteoporosis in men.
AB  - Though commonly seen as a disease afflicting only women, osteoporosis affects
      more than 5 million men in the United States with significant morbidity and
      mortality. Alcohol abuse, glucocorticoid excess, and hypogonadism are the
      principle risk factors for osteoporosis in men. Radiographs alone are
      insufficient in detecting the presence of the disease. Examining bone mineral
      density is the diagnostic standard used to detect the disease in both men and
      women. Unfortunately, diagnostic parameters and screening recommendations for
      bone mineral density testing have not been firmly established in men. The
      treatment and prevention of osteoporosis has been well studied in women, thus
      many of the treatments for men with the disease were extrapolated from studies
      predominantly involving women. Prevention of osteoporosis in men is best directed
      toward risk-factor modification and supplementation with calcium and vitamin D.
      The mainstay of treatment is bisphosphonates such as alendronate that have
      demonstrated both efficacy and safety in studies. Vitamin D and calcium
      supplementation also has some benefit in treating men with osteoporosis.
      Parathyroid hormone, thiazide diuretics, and calcitonin may also have a role in
      the prevention and treatment of osteoporosis in men, although this is not yet
      firmly established.

PMID- 12503225
TI  - The positive deviance approach to improve health outcomes: experience and
      evidence from the field. Introduction.

PMID- 12503226
TI  - Positive deviant behavior and nutrition education.

PMID- 12503227
TI  - Ti Foyer (Hearth) community-based nutrition activities informed by the positive
      deviance approach in Leogane, Haiti: a programmatic description.
AB  - This paper details the steps to design and implement a positive deviance
      informed, "Hearth" approach for the nutritional rehabilitation of malnourished
      children in the district of Leogane, Haiti. Groups of four to five children met
      daily for two weeks at the home of a local volunteer mother for nutritional and
      health messages and a well-balanced meal. Health messages and meal components
      were determined using information gathered from interviews with the mothers of
      positive deviant children in the community who are well nourished despite their
      family's limited economic resources. Hearth participants were then followed for
      six months in their own home by the program "monitrices," women hired from each
      village and intensively trained to supervise the Hearth program, periodically
      weigh the children to evaluate their progress, and liaise between the hospital
      and the community. Monitoring from the first cycle indicated that 100% of
      children in eight villages and 66% of children in the remaining five villages
      continued to gain weight as fast or faster than the international standard median
      six months after participating in a Hearth program. At the conclusion of this
      cycle, programmers interviewed participant and non-participant families and made
      six modifications to the model, including the addition of a microcredit option
      for participating mothers.

PMID- 12503228
TI  - Sustained positive deviant child care practices and their effects on child growth
      in Viet Nam.
AB  - Save the Children's (SC) successful integrated nutrition program in Viet Nam, the
      poverty alleviation and nutrition program (PANP), uses the positive deviance (PD)
      approach to identify key growth promoting behaviors and provides participatory
      adult education allowing mothers to develop skills related to these behaviors. We
      investigated whether improvements seen during a PANP intervention (1993-1995)
      were sustained three and four years after SC's departure. Cross-sectional surveys
      were administered to 46 randomly selected households in four communes that had
      previously participated in the PANP and 25 households in a neighboring comparison
      community in 1998 and 1999. Two children per household, an older child who had
      participated in the PANP and a younger sibling who had not, were measured (total
      n = 142 children), and their mothers were interviewed. Older SC children tended
      to be better nourished than their counterparts. Their younger siblings were
      significantly better nourished than those in the comparison group, with adjusted
      mean weight-for-age Z scores of -1.82 versus -2.45 (p = .007), weight-for-height
      Z scores of -0.71 versus -1.45 (p < .001), and height-for-age Z scores of -2.11
      and -2.37 (ns, p = .4), respectively. SC mothers reporting feeding the younger
      siblings more than their counterparts did (2.9 versus 2.2 main meals per day, p <
      .001, and 96.2% versus 52% offering snacks, p < .01). SC mothers reported washing
      their hands "often" more than comparison mothers (100% vs. 76%, p < .001). Growth
      promoting behaviors identified through PD studies and practiced through
      neighborhood-based rehabilitation sessions persisted years after program
      completion. These sustained behaviors contributed to better growth of younger
      siblings never exposed to the program.

PMID- 12503229
TI  - Comparison of a positive deviance inquiry with a case-control study to identify
      factors associated with nutritional status among Afghan refugee children in
      Pakistan.
AB  - We compared the positive deviance (PD) approach in Save the Children's field
      guide with a case-control study (CCS) to identify behaviors associated with good
      nutritional status in Afghan refugee children 6 to 24 months of age in the
      Northwest Frontier Province (NWFP), Pakistan. The positive deviance inquiry
      (PDI), utilizing observations and interviews with mothers, fathers, and secondary
      caregivers in eight households, identified 12 feeding, caring, and health-seeking
      behaviors that were not widely practiced. The CCS, using the same selection
      criteria and content as the PDI with 50 mother-child pairs not in the PDI,
      yielded six significant associations with good nutritional status. Both the PDI
      and CCS detected feeding behaviors. The PDI alone identified complex phenomena
      (active feeding and maternal affect). The CCS alone confirmed the beneficial use
      of health services. The PD approach was an affordable, participatory, and valid
      method to identify feeding behaviors and other factors associated with good
      nutrition in this context.

PMID- 12503230
TI  - Design of a prospective, randomized evaluation of an integrated nutrition program
      in rural Viet Nam.
AB  - Few prospective studies of child growth and its determinants take place in
      programmatic contexts. We evaluated the effect of Save the Children's (SC)
      community empowerment and nutrition program (CENP) on child growth, care,
      morbidity, empowerment, and behavioral determinants. This paper describes the
      research methods of this community-based study. We used a longitudinal,
      prospective, randomized design. We selected 12 impoverished communes with
      documented child malnutrition, three comparison, and three intervention communes
      in each of two districts in Phu Tho Province, west of Hanoi. SC taught district
      trainers in November 1999 to train local health volunteers to implement the 10
      month CENP, including situation analysis, positive deviance (PD) inquiry, growth
      monitoring and promotion, nutrition education and rehabilitation program (NERP),
      deworming, and monitoring. PD inquiries aim to discover successful care practices
      in poor households that likely promote well-nourished children. NERPs are
      neighborhood-based, facilitated group learning sessions where caregivers of
      malnourished children learn and practice PD and other healthy behaviors. We
      dewormed all intervention and comparison children. We randomly selected 240
      children 5 to 25 months of age (120 intervention and 120 comparison). We gathered
      information on nutritional status, diet, illness, care, behavioral determinants,
      empowerment, and program quality, monthly for six months with a re-survey at 12
      months. We collected most information through maternal interview but also
      observed hygiene and program quality, and videotaped feedings at home. Some
      implementation and research limitations will attenuate CENP impact and
      measurement of its effectiveness.

PMID- 12503231
TI  - Weighing Vietnamese children: how accurate are child weights adjusted for
      estimates of clothing weight?
AB  - Children who are weighed for growth monitoring are frequently clothed, especially
      in the cold weather. Health workers commonly estimate and subtract the weight of
      these clothes, but the accuracy of these estimates is unknown. We assessed the
      accuracy of child weights adjusted for estimated clothing typical of hot, cold,
      and extremely cold ambient temperatures. Trained field workers weighed a sample
      of 212 children 6 to 42 months old from the ViSION project, adjusted the weights
      using a job aid describing the weights of common clothing by season and age, and
      then weighed the clothing to calculate the actual clothing and child weights.
      Fieldworker estimates of the weight of the clothing that children wore during
      weighing were remarkably good. In nearly all cases (207 of 212; 97.7%), the
      difference between the estimated and actual clothing weight was less than the
      precision of the child scales (+/- 50 g), and most (181 of 212; 84.5%) were
      within 25 g. Thus, the calculated child weights were, in fact, equivalent to the
      actual child weights. Using simulations, we found that improperly accounting for
      clothing weight can overestimate weight-for-age by 0.1 to 0.4 Z score. Accurate
      weights are possible, even under adverse conditions. Our training methods,
      clothing album, and job aid might benefit nutrition research and programming in
      Viet Nam as well as settings with colder climates.

PMID- 12503232
TI  - An integrated child nutrition intervention improved growth of younger, more
      malnourished children in northern Viet Nam.
AB  - Integrated nutrition programs are widely used to prevent and/or reverse childhood
      malnutrition, but rarely rigorously evaluated. The impact of such a program on
      the physical growth of young rural Vietnamese children was measured. We
      randomized six communes to receive an integrated nutrition program implemented by
      Save the Children. We matched six communes to serve as controls. Our sample
      consisted of 238 children (n = 119 per group) who were 5 to 25 months old on
      entry. Between December 1999 and December 2000, we measured weight and height
      monthly for seven months and again at month 12. Principle outcomes were weight
      for-age Z score (WAZ), height-for-age Z score (HAZ), and weight-for-height Z
      score (WHZ), and the changes among these measures. As expected, anthropometric
      indicators relative to international references worsened as the children aged.
      Overall, children in the intervention communes who were exposed to the integrated
      nutrition program did not show statistically significant better growth than
      comparison children. Intervention children who were younger (15 months or less)
      and more malnourished (less than-2 Z) at baseline, however, deteriorated
      significantly less than their comparable counterparts. Between baseline and month
      four, for example, intervention children who were malnourished and less than 15
      months old at entry lost on average 0.05 WAZ while similar comparison children
      lost 0.25 WAZ (p = .02). Lack of overall impact on growth may be due to a lower
      than expected prevalence of malnutrition at baseline and/or deworming of
      comparison children. Targeting nutrition interventions at very young children
      will have the maximum impact on growth.

PMID- 12503233
TI  - Effect of an integrated child nutrition intervention on the complementary food
      intake of young children in rural north Viet Nam.
AB  - Forty-two percent of Vietnamese children are stunted by two years of age. Since
      1990, Save the Children Federation/US (SC) has implemented integrated nutrition
      programs targeting young children. We evaluated the effect of SC's nutrition
      program on the complementary food intake of young rural Vietnamese children.
      Using a longitudinal, prospective, randomized design, we followed 238 children
      (119 each from intervention and comparison communes) age 5 to 25 months old for
      six months with a re-survey at 12 months. We gathered 24-hour recall data at
      baseline and at months 2, 4, 6, and 12. Dietary energy intake was calculated
      using the 1972 Vietnamese food composition table. Key outcomes were daily
      frequency of consuming intervention-promoted food and non-breastmilk liquids and
      food, daily quantity of non-breastmilk liquids and food consumed, daily energy
      intake, and proportion of children meeting daily median energy requirements.
      Young rural children exposed to SC's program consumed intervention-promoted, and
      any, foods more frequently, ate a greater quantity of any food, consumed more
      energy, and were more likely to meet their daily energy requirements than
      comparison children. Some effects were only observed during the intensive
      intervention period; others persisted into or were evident only at the 12-month
      follow-up, approximately four months after program completion. Based on the
      mothers' reports, the intervention did not apparently compromise breastfeeding
      prevalence or frequency. The intervention improved children's food and energy
      intake and protected them from declining as rapidly as comparison children in
      meeting their energy requirements.

PMID- 12503234
TI  - Effect of an integrated nutrition program on child morbidity due to respiratory
      infection and diarrhea in northern Viet Nam.
AB  - Infectious disease and poor diet are the two proximal causes of malnutrition in
      children. During the 1990s, integrated nutrition programs implemented by Save the
      Children (SC) in Viet Nam reduced severe child malnutrition, but it has not been
      clear if this impact was due primarily to improved diet or reduced disease. The
      aim of this study was to determine whether a community-based, integrated
      nutrition program in Viet Nam reduced child morbidity due to diarrhea or acute
      respiratory infections. Children 5 to 25 months old were randomly selected from
      randomly assigned intervention and comparison communes. Caregivers of children
      from the intervention and comparison groups (n = 119 per group) were interviewed
      about their child's morbidity at program baseline and at study months 2, 4, 6,
      and 12. Multiple logistic regression and general estimating equations (GEE) were
      used to evaluate the effect of the intervention on the occurrence of any diarrhea
      and respiratory illness in the preceding two weeks. Respiratory illness, mainly
      upper respiratory illness, was more common than diarrheal disease at baseline
      (54% vs. 6%, respectively). During follow-up, children in the intervention
      communes had approximately half the respiratory illness experienced by those in
      comparison communes (AOR = 0.5; p = .001). Diarrheal disease was also lower in
      the intervention group, although differences were not statistically significant.
      We conclude that SC's integrated nutrition program was associated with reduced
      upper respiratory illness, perhaps due to improved hygiene practices and/or
      improved micronutrient intakes.

PMID- 12503235
TI  - Implementation of nutrition education and rehabilitation programs (NERPs) in Viet
      Nam.
AB  - Rigorous assessments of program quality are uncommon in developing countries. We
      evaluated the quality of the two-week, volunteer-facilitated, caregiver-child
      rehabilitation "hearth," or nutrition education and rehabilitation program
      (NERP), sessions in Save the Children's integrated nutrition program in Viet Nam.
      Field workers observed attendance, food contribution, food preparation, meal
      consumption, health message delivery, hygiene, and weighing at 240 NERP days at
      59 NERP centers during seven months of implementation. Participation in cooking
      NERP meals (75.8%), washing mothers' and children's hands (75.7% and 81.6%,
      respectively), and weighing (74.5% on days 1 and 12) were high, but attendance
      rates (50.3%), food contributions (20.3%), and health message delivery (20.0%)
      were lower than expected, all with wide variation among communes, ecology, NERP
      day, and NERP round. Contrary to protocol, food was often delivered to
      malnourished children who stayed at home to accommodate caregivers' workloads and
      other constraints. While home-delivery of food prevented caregivers from learning
      from each other in a group, it did bring "tangible messages" (i.e., a large
      serving size of a new food) to the doorstep. Health volunteers were wise to
      stress active learning over repetitive message delivery. In summary, these NERPs
      were probably typical of previous NERPs although comparable quality measures are
      lacking. Despite imperfect implementation, the NERP's active-learning and local
      problem-solving helped achieve measurable impact on growth, diet, morbidity, and
      empowerment despite uncommon program challenges, such as uncharacteristically low
      baseline levels of malnutrition and high population dispersion. Regular quality
      monitoring may enhance impact even further.

PMID- 12503236
TI  - Empowerment in rural Viet Nam: exploring changes in mothers and health volunteers
      in the context of an integrated nutrition project.
AB  - Empowerment is often cited as a fundamental component of health promotion
      strategies. Anecdotes suggest that Save the Children's integrated nutrition
      project empowers local women and health volunteers. The aim of this research was
      to document the degree to which this is being accomplished. Using qualitative
      methodologies, we conducted a cross-sectional assessment to compare self-reported
      changes in identified empowerment domains among 17 program health volunteers and
      20 mothers involved in a child nutrition intervention and among five Women's
      Union leaders and five mothers in a non-intervention comparison commune.
      Intervention mothers reported increased knowledge, confidence, and information
      sharing about child-care and feeding, while non-intervention mothers reported
      minimal changes in these domains. Both intervention health volunteers and non
      intervention Women's Union leaders expressed improvements in knowledge,
      confidence, and relationships with community members. In this study we found that
      the relative increases in empowerment were greater for mothers than for health
      volunteers. Intervention mothers reported more sharing of information on child
      care with neighbors. Health volunteers developed closer relationships with
      community members than Women's Union leaders. The increased information sharing
      has positive implications for spread of key messages to families that did not
      directly participate in intensive feeding and the sustainability of the
      intervention's impact. Future research should focus on developing culturally
      specific concepts of empowerment to better understand the effects of empowerment
      efforts. This study's identification of empowerment domains will inform future
      empowerment studies in Vietnam.

PMID- 12503237
TI  - Caregiver styles of feeding and child acceptance of food in rural Viet Nam.
AB  - Style of child feeding may be an important determinant of child nutrition and
      health outcomes. Responsive feeding refers to the level and kind of interaction
      between caregiver and child that lead to a positive feeding experience, adequate
      dietary intake, and enhanced developmental opportunities. Responsive feeding
      behaviors may include active physical help and verbalization during feeding, role
      playing, persistence, and positive feeding strategies. The aim of this study was
      to investigate styles of feeding among Vietnamese children 12 or 17 months of age
      from a rural province in northern Viet Nam. Forty child/mother pairs were
      videotaped during two, two-hour feeding episodes. Caregiver and child behaviors
      were coded at the level of the "intended bite" as observed through the videotape
      analysis of feeding episodes to assess caregiver behavior and the child's
      interest and acceptance of food. We found it feasible to use videotape and the
      modified coding and analysis scheme, originally developed for work in Peru, in
      Viet Nam. In Viet Nam, caregivers provided physical help to eat nearly all of the
      time for the younger children, and about 70% of the time among 17 month olds.
      Caregivers verbalized during only 30% of intended bites, and only half of these
      verbalizations were responsive in tone or words. Positive caregiver behaviors
      were significantly associated with higher child acceptance of food, while non
      responsive feeding behaviors were associated with child rejection of food. Future
      analyses of this data set will evaluate the degree to which an integrated
      nutrition program positively modified caretaker behaviors. More research is
      needed to demonstrate the relationships among the promotion of responsive feeding
      behaviors, acceptance of food, and improved nutrition and health status of
      children.

PMID- 12503238
TI  - Work outside the home is the primary barrier to exclusive breastfeeding in rural
      Viet Nam: insights from mothers who exclusively breastfed and worked.
AB  - This study assessed barriers to exclusive breastfeeding in rural Viet Nam and
      identified how a few mothers were able to exclusively breastfeed despite
      barriers. A cross-sectional quantitative and qualitative assessment was carried
      out among 120 mothers of infants less than six months old in northern Viet Nam.
      Only 24% of the mothers exclusively breastfed. Adjusting for infant's age and who
      attended delivery, the risk of not exclusively breastfeeding was 14.0 times
      greater for women who had returned to work than for women who had not.
      Exclusively breastfeeding mothers (n = 4) who worked differed from other mothers
      in important ways. They all felt they had enough milk, all knew the appropriate
      time to introduce foods and liquids, and most were supported in their
      breastfeeding decisions by commune health workers and family members. This
      research suggests strategies that can be implemented now to increase exclusive
      breastfeeding in rural work environments. These include improving knowledge about
      the introduction of water and semi-solids, addressing perceptions of milk
      insufficiency, securing support from others, and presenting mothers with options
      for exclusively breastfeeding, even when they work outside the home.

PMID- 12503239
TI  - Identification of model newborn care practices through a positive deviance
      inquiry to guide behavior-change interventions in Haripur, Pakistan.
AB  - A positive deviance (PD) inquiry identifies uncommon, model practices that a
      follow-on program can spread. PD has been used to rehabilitate malnourished
      children, but not for improving newborn health. Save the Children Federation/US
      (SC) conducted newborn PD cycles in communities (total population about 5,000
      each) in two project areas in Haripur District, Pakistan among Afghan refugees
      and among local Pakistanis. Each PD cycle included planning, community
      orientation, situation analysis, PD inquiries, and community feedback with action
      planning. PD inquiries were in-depth interviews to identify uncommon behaviors
      among surviving asphyxiated newborns, thriving low birthweight babies, surviving
      newborns who had danger signs, and normal newborns. The Afghan caregivers showed
      better use of services and some household practices than their Pakistani
      counterparts, consistent with duration of SC presence (15 years vs. 18 months,
      respectively). The practices of both groups for clean delivery, thermal control,
      immediate and exclusive breastfeeding, and fathers' involvement were weak. But PD
      individuals, families, and/or birth attendants modeled good maternal care and
      immediate, routine and special newborn care. Communities enthusiastically
      committed to change behavior and form neighborhood support groups for better
      newborn care, including a demand for hygienic delivery. The PD approach for the
      newborn is more complex than for child nutrition. Yet this pilot-test proposed a
      conceptual framework for household newborn care, suggested tools and methods for
      information gathering, identified PDs in two settings of different risk,
      galvanized SC staff to the potential of the approach, mobilized communities for
      better newborn health, and drafted a newborn PD training curricula.

PMID- 12503240
TI  - What influences health behavior? Learning from caregivers of young children in
      Viet Nam.
AB  - Globally, the caregiving behaviors that contribute to good nutritional status are
      well understood; but it is not clear why some caregivers perform these behaviors
      while others do not. This formative qualitative research was designed to improve
      understanding about what distinguishes caregivers who practice optimal behaviors
      from those who do not. This study is a one-time, cross-sectional baseline
      assessment of factors that affect nutrition-related behavior change. It took
      place in a rural northern province in Viet Nam. One hundred caregivers of
      children 6 to 17.9 months of age from five communes were interviewed. None of the
      five communes were included in the larger prospective study designed to test the
      impact of the Community Empowerment and Nutrition Program (CENP). Four behaviors
      were examined: feeding the child "positive deviant" foods, feeding the child
      during diarrheal episodes, washing the child's hands, and taking the child to the
      health center when ill. Results indicate that for all four behaviors, favorable
      social norms distinguished those who practiced each behavior from those who did
      not. Positive, reinforcing beliefs and attitudes were important determinants of
      every behavior except handwashing Likewise, self-efficacy differentiated doers
      from non-doers for all behaviors except feeding during diarrheal episodes.
      Findings from this research suggest that fathers and in-laws of non-doers are
      more likely to fail to advise mothers about infant feeding and health than they
      are to provide negative advice. By discovering what distinguishes those who
      practice optimal behaviors from those who do not, researchers, program planners,
      and others are better equipped to develop targeted interventions that lead to
      positive behavior change.

PMID- 12503241
TI  - The positive deviance approach: challenges and opportunities for the future.
AB  - The positive deviance (PD) approach offers an alternative to needs-based
      approaches for development. The "traditional" application of the PD approach for
      childhood malnutrition involves studying children who grow well despite
      adversity, identifying uncommon, model practices among PD families, and designing
      an intervention to transfer these behaviors to the mothers of malnourished
      children. A common intervention for child malnutrition, the so-called "hearth,"
      brings mothers together to practice new feeding and caring behaviors under the
      encouragement of a village volunteer. Hearths probably work because they modify
      unmeasured behavioral determinants and unmonitored behaviors, which, in turn,
      result in better child growth. Some health outcomes require a better
      understanding of behavioral determinants and are not best served by hearth-like
      facilitated group skills-building. We propose testing "booster PD inquiries"
      during implementation to confirm behavioral determinants and efficiently focus
      interventions. We share early experience with the PD approach for HIV/AIDS and
      food security. The attributable benefit of the PD approach within a program has
      not been quantified, but we suspect that it is a catalyst that accelerates change
      through the processes of community attention getting, awareness raising, problem
      solving, motivating for behavior change, advocacy, and actual adopting new
      behaviors. Program-learners should consider identifying and explicitly attempting
      to modify the determinants of critical behavior(s), even if the desired outcome
      is a change in health status that depends on multiple behaviors; measure and
      maintain program quality, especially at scale; and creatively expand and test
      additional roles for PD within a given program.

PMID- 12503242
TI  - Individual Social Security accounts. Administrative issues.

PMID- 12503243
TI  - [Role of transcranial magnetic stimulation in clinical diagnosis: motor-evoked
      potential (MEP)].
AB  - Transcranial magnetic stimulation allows painless, non-invasive stimulation,
      neurophysiological evaluation of nervous structure covered by bone or difficult
      to access for other reasons. In the clinical setting the technique is mainly used
      for the investigation of the corticospinal tract (motor evoked potential: MEP).
      Based upon our experience with patients examined over the course of four years,
      we have attempted to highlight the clinical situations, where diagnostic help is
      provided by this technique. MEP in general has proved to be a sensitive and
      reliable examination. Its significance is apparent mainly in situations where
      clinical signs of corticospinal tract dysfunction are not evident, or they are
      masked by lower motoneurone involvement, and where neuroimaging techniques are
      not informative. The demonstration of subclinical corticospinal lesion is often
      essential to establish the diagnosis in multiple sclerosis and amyotrophic
      lateral sclerosis. The technique however received little attention so far with
      respect to its role in the diagnosis of various spinal cord disorders, and in the
      demonstration of intact corticospinal function in case of weakness, psychogenic
      in origin. We have endeavored to provide further evidence in support of this, and
      thereby advocating a wider clinical application of the technique.

PMID- 12503244
TI  - Anxiety in epilepsy--based on two case reports.
AB  - There are a great number of psychopathological symptoms which manifest themselves
      in 70-75% of epileptic patients but most of them remain unrecognised and
      untreated. These symptoms may affect the patients' quality of life more
      negatively than the epileptic seizures themselves. Anxiety is one of the most
      frequently occurring interictal psychopathological symptom. A number of
      specialists agree that chronic epilepsy causes the amplification of endogenic
      seizure suppressing mechanisms which hinder the epileptic seizures and are
      responsible for the development of interictal psychopathological symptoms.
      However the physiological effects of the interictal psychopathological conditions
      (e.g. anxiety) have epileptogenic effect as well. There is a high chance that the
      conditions of epilepsy and anxiety will mutually create a destructive vicious
      circle and it will be illustrated by our two case reports. In our experience,
      before modifying the pharmacotherapy of a patient suffering from chronic epilepsy
      with increased frequency of seizures, the anxiety level should be defined; and if
      it is high it should be treated first. From our perspective, the so-called
      "rational bitherapy" is very effective when a high potential antiepileptic drug
      is combined with an anxiety reducing method. The latter can be drug related or
      consists only of psychotherapy. We need more controlled clinical research to
      prove that inside epilepsy there are risk groups as well as conditions of high
      risk when the connection between anxiety and epilepsy is more than evident. The
      described cases seem to indicate that the existence of periictal anxiety can be a
      risk factor in developing later interictal anxiety.

PMID- 12503245
TI  - [Analgesic effect of kynurenic acid].
AB  - It is well known that glutamate receptors have significant role in the pain
      transmission. The activation of N-methyl-D-aspartate receptors causes persistent
      pain, therefore the antagonists acting on these receptors cause antinociception
      in chronic pain states. As the synthetic N-methyl-D-aspartate receptor
      antagonists have several side effects, they are not used generally in the
      clinical therapy. The tryptophan metabolite kynurenic acid is an endogenous
      antagonist of N-methyl-D-aspartate receptors. Although some data proved its
      neuroprotective effect, only a few studies suggest the antinociceptive potential
      of kynurenic acid. The goal of this review to summarise the possible role of
      kynurenic acid in the pain therapy based on the results of animal studies. Data
      available concerning this subject demonstrated that kynurenic acid is not an
      appropriate agent for antinociception neither in single nor in continuous
      administration because of its side-effect resulting in motor deficiency. On the
      other hand the combination of low doses of kynurenic acid and endomorphin-1
      provides effective antinociception without side-effects on inflammatory pain
      test, thus may offer a new treatment modality in human pain therapy.

PMID- 12503246
TI  - [Kennedy syndrome--bulbo-spinal muscular atrophy].
AB  - Kennedy syndrome is a late-onset, bulbar-spinal type of muscular atrophy, with X
      linked recessive inheritance. The characteristic features of the disease become
      prominent in the 4-5th decades: proximal muscle wasting and weakness, bulbar
      signs, fasciculations in skeletal muscles, subtle signs of endocrine dysfunction,
      such as gynaecomastia or testicular atrophy. The electrophysiological
      examinations are the keypoint to the diagnosis. Electroneurography shows normal
      conduction velocity in peripheral nerves, but the sensory nerves usually show
      axonal degeneration, which causes only very mild or subclinical neurological
      deficits. Electromyography shows chronic anterior horn cell degeneration in
      skeletal muscles. Molecular genetic diagnosis was introduced in 1991, when on
      abnormal expansion of CAG repeat was found in the first exon of the androgen
      receptor gene on chromosome X with a frequency of 100% in the affected
      population. Since the progression is very slow and these patients can expect a
      normal life span, it is essential to distinguish this syndrome from other, often
      more severe diseases, such as ALS. There is no proven therapy for Kennedy's
      disease yet. This is the first case of Kennedy's disease published in Hungary.

PMID- 12503247
TI  - [Molecular genetics of affective disorders].

PMID- 12503248
TI  - [Role of epileptogenic lesions in interictal and ictal functional disorders in
      epilepsy].

PMID- 12503249
TI  - [Dezso Miskolczy--founder of modern neurology in Hungary].

PMID- 12503251
TI  - Toxicity of the Chinese herb mu tong (Aristolochia manshuriensis). What history
      tells us.
AB  - Plant sources of some traditional Chinese herbs may have changed over time.
      History records of herbal toxicity should be viewed critically when different
      plants might have been used under the same name in earlier eras. The current main
      source of the Chinese herb Mu Tong is Aristolochia manshuriensis. Examination of
      classical Chinese herbal literature revealed that until the mid 17th century the
      original source plants of Mu Tong had been several Akebia species. From the 17th
      century until the early 20th century Clematis species were the main source of Mu
      Tong. A manshuriensis has only been widely used since the 1950s. Renal failure
      due to ingestion of large doses of A. manshuriensis has been reported in China
      and other countries while no such toxicity has been recorded in traditional
      Chinese herbal texts. Documentation of traditional Chinese herbal literature
      should help to ensure the safe use of Chinese herbs.

PMID- 12503252
TI  - Citalopram-induced severe hyponatraemia with coma and seizure. Case report with
      literature and spontaneous reports review.
AB  - Numerous case reports of hyponatraemia followed increasing use of selective
      serotonin re-uptake inhibitors (SSRIs) but this adverse effect was only rarely
      observed in relation to citalopram. We report a case of severe hyponatraemia
      associated with deep coma, seizure, atrial fibrillation and muscle damage in a 92
      year-old woman after only two doses of citalopram, and review 14 cases previously
      published in the literature and 28 cases spontaneously reported to Australian
      Drug Reaction Advisory Committee (ADRAC). The data presented suggest that
      citalopram, as well as SSRIs may cause hyponatraemia secondary to syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH). The majority of
      symptomatic cases occurred in elderly patients (79% were older than 70 years) and
      in women (74%). Polymedication and concomitant use of another psychotropic drug
      or thiazide diuretic may precipitate and/or augment the development of
      hyponatraemia/SIADH. In 84% of cases, the hyponatraemia associated with
      citalopram was detected during the first month of treatment. High level of
      suspicion, close and careful monitoring of serum sodium concentration
      particularly in elderly patients and especially in the first month of therapy
      with citalopram may reduce the incidence of this serious and likely not rare
      adverse effect.

PMID- 12503253
TI  - Investigation of the potential of clozapine to cause torsade de pointes.
AB  - Antipsychotics are frequently associated with QTc interval prolongation, a
      proposed marker for vulnerability to fatal ventricular arrhythmias, e.g. torsade
      de pointes (TdP). Little has been published on this topic in relation to
      clozapine. The objectives of this review were to: (i) calculate the frequency of
      QTc interval prolongation, T-wave abnormalities, TdP, ventricular
      tachycardia/fibrillation and sudden unexplained death in patients treated with
      clozapine and thioridazine from clinical trial and post-marketing reports; (ii)
      to compare these data with published findings for haloperidol, risperidone,
      olanzapine, sertindole and ziprasidone; and (iii) to correlate these clinical
      data with results from preclinical tests presently considered to be of predictive
      value for a compound's potential to cause QTc interval prolongation and TdP. A
      review of the global Novartis databases for clozapine and thioridazine and a
      Medline/Internet search for information on these cardiac events and for
      preclinical effects on the human ether-a-go-go related gene channels, action
      potential duration, and QT interval changes produced by the selected
      antipsychotics were performed. The clozapine database (2.8 million patient-years
      spanning 27 years) demonstrated that at therapeutic doses all but three reports
      of QTc interval prolongation and both of TdP were confounded by relevant co
      medication/comorbidity. The literature review revealed that all antipsychotics
      considered except clozapine induced TdP and/or QTc interval prolongation at
      therapeutic doses. Preclinical in vitro tests appear to overestimate the risk of
      clozapine, haloperidol and risperidone to prolong QTc interval in patients and
      underestimate such a risk for sertindole and ziprasidone. Extrapolation of in
      vitro results to clinical events requires qualified interpretation.

PMID- 12503254
TI  - Are hypoglycaemia and other adverse effects similar among sulphonylureas?
AB  - This review provides an updated overview of the adverse effects of sulphonylureas
      and identifies factors associated with variation in adverse effect rates among
      sulphonylureas published by different studies. A search of Medline, Embase,
      Current Contents and Cochrane Library was conducted to identify all papers
      related to sulphonylureas and adverse effects published from 1950-2001. The
      reference lists of all relevant papers were also searched for additional
      articles. The frequency of sulphonylurea-induced hypoglycaemia varied from 1.8
      59%. Severe hypoglycaemia due to sulphonylurea use has been reported from 1.9
      3.5%. Variation in hypoglycaemia rates may be due to differences in definitions,
      methods to detect and to collect information, patient characteristics, patient
      knowledge of the condition, threshold for symptoms, and activity level during
      hypoglycaemia. Other adverse effects associated with sulphonylurea use include
      bodyweight gain, gastrointestinal distress, disulphiram-like syndrome,
      dermatological reactions, haematological changes, ocular problems, and the
      syndrome of inappropriate secretion of antidiuretic hormone. Bodyweight gain has
      been reported to vary from 1.7-4.8 kg, according to the United Kingdom
      Prospective Diabetes Study (UKPDS-33). Controversy exists regarding
      cardiovascular adverse effects, but the consensus is to exercise caution in the
      use of these drugs as first-line therapy for patients with diabetes mellitus and
      coronary artery disease. The benefits of sulphonylurea treatment should be
      weighed against the risks associated with them. More work in this area is needed
      to homogenise the definition of hypoglycaemia, to get consensus on the methods
      for detection and data collection, as well as to further patient and physician
      education.

PMID- 12503255
TI  - How natural are 'natural herbal remedies'? A Saudi perspective.
AB  - OBJECTIVE: There is a rapidly growing trend in the consumption of herbal remedies
      in industrialised and developing countries. Users of herbal remedies are at risk
      of toxicity and adverse interactions of herbal preparations due to their frequent
      contamination with metals and adulteration with synthetic drugs. The purpose of
      this study was to assess the quality of herbal remedies present on the market in
      Saudi Arabia in recent years. METHODOLOGY: 247 herbal remedies and related
      preparations were examined from 2000-2001 at the Toxicology Laboratory, King
      Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Herbal
      powder samples were the most common sample type examined (n = 80), followed by
      complete, packed preparations (n = 59), single undescribed capsules or pills (n =
      46), loose plant leaves or seeds (n = 28), creams (n = 18) and liquid or jelly
      samples (n = 16). All samples were subjected to toxicological screening for
      organic substances using gas chromatographic-mass spectrometric analysis,
      screening for heavy metals (arsenic, mercury, and lead) using inductive coupled
      plasma-mass spectrometry and microbiological examination. RESULTS: The
      preparations analysed were used to treat the following indications: leukaemia and
      other forms of cancer (n = 22); obesity (n = 18); diabetes mellitus (n = 14);
      rheumatic disorders (n = 14); skin pigmentation problems (n = 11); or to enhance
      male sexual activity (n = 9). In 123 cases, the indication of use was not known.
      39 samples contained high concentrations of heavy metals. This was particularly
      striking in remedies used to treat leukaemia (arsenic content of 522-161,600 ppm)
      and in creams for whitening skin (mercury content of 5,700-126,000 ppm). Eight
      preparations contained synthetic drugs (e.g. benzodiazepines and tricyclic
      antidepressants in sedative preparations, cyproheptadine in a remedy to gain
      bodyweight, ibuprofen and dipyrone in herbal capsules used to treat rheumatism).
      18 samples were contaminated with micro-organisms. 14 samples contained toxic
      substances of natural origin. Of the 247 examined preparations, 77 (i.e. over
      30%) were disqualified due to high heavy metals content, bacterial contamination
      or presence of toxic organic substances. CONCLUSION: The study shows an urgent
      need to control the production, importing and selling of herbal preparations.

PMID- 12503256
TI  - Review of national spontaneous reporting schemes. Strengths and weaknesses.
AB  - OBJECTIVE: To investigate and compare the operation of different national
      spontaneous reporting schemes for adverse drug reactions. DESIGN: Drug safety
      agencies in 18 countries were contacted by letter to request information about
      their spontaneous reporting scheme for adverse drug reactions. This information
      related to the background of the scheme, operational aspects of the scheme and
      numbers of reports received. RESULTS: Replies were received from 12 countries.
      Many differences were found between the schemes operating in different countries.
      Some schemes had been in operation for over 30 years, while others were more
      recently established. While most schemes rely on voluntary reports, in two
      countries (France and Spain), reporting is a legal requirement for healthcare
      professionals. Reports are accepted from doctors, dentists and pharmacists in all
      of the countries surveyed; however the role of other health professionals and the
      general public was found to vary. There were also differences in the types of
      reactions for which reports are requested, and the products covered by the
      schemes. In some countries (e.g. Denmark) reports of all reactions are sought,
      while other countries focus on only serious reactions or reactions to newly
      marketed products. In Australia, there is a separate scheme for drug-induced
      congenital malformations and Canada, South Africa and the US run separate schemes
      for reactions to vaccines. However, other countries include these reactions in
      the general spontaneous reporting schemes. The numbers of reports received by the
      countries also varies considerably--from a few hundred each year in South Africa
      to over 20,000 in the US. CONCLUSION: While the schemes all operate on the basic
      principle of collecting reports of adverse reactions to identify potential
      hazards, they showed many different approaches to the spontaneous reporting of
      adverse drug reactions. Features of one scheme may serve to improve reporting
      rates for another. In addition, all 12 countries participate in the World Health
      Organization International Drug Monitoring Programme, thus helping to inform the
      whole international community of drug safety problems.

PMID- 12503257
TI  - The life of Andrew Boorde, c1490-1549.
AB  - Physician, traveller, writer and spy, Andrew Boorde was born c1490 and became a
      Carthusian monk after abandoning his medical studies at Oxford. Temperamentally
      unsuited to the life of a religious, after 20 years at the London Charterhouse he
      obtained a dispensation to travel to Europe to continue his medical studies.
      Returning to England he began to practise medicine, treating members of the
      nobility and, through a meeting with Thomas Cromwell which was to influence the
      rest of his life, he attended the King, Henry VIII. In 1534, after a second, more
      extensive, tour of Europe in which he visited many medical schools and
      universities seeking yet more medical knowledge, he returned to the London
      Charterhouse which was undergoing a brutal dissolution at the hands of Thomas
      Cromwell. Boorde reluctantly signed the Oath of Supremacy, an act which was to
      haunt him for the rest of his life. He was then used by Cromwell to travel abroad
      again but this time as a spy to gather intelligence for the King while continuing
      to study medicine. Boorde finally took his MD at the University of Montpellier
      and was incorporated in the same degree a year later at Oxford. He then gave
      expression to all he had learnt by writing his legacy, four books which were
      published in 1547. 'A Compendyous Regyment or a Dyetary of Health' was one of the
      earliest treatises on the cultivation of health composed in England and stressed
      the importance of sanitation together with a detailed examination of diet. The
      'Brevyary of Health' listed diseases alphabetically together with remedies and
      treatment, blending sound medical advice with religion and superstition: its
      companion volume was 'The Principles of Astronomy'. But Boorde's 'Fyrst Boke of
      the Introduction of Knowledge' was his tour-de-force; it was a comprehensive
      encyclopaedia of all the European countries he had visited, illustrated by
      woodcuts. By 1547 Boorde was settled in England, probably Master of the Hospital
      of St Giles-in-the-Fields in London but by 1549 he was living the life of a
      recluse in Winchester. Tortured by guilt at his perceived lack of religious
      integrity and persecuted by his enemies he died in the Fleet prison amid rumors
      that he had poisoned himself.

PMID- 12503258
TI  - Adverse drug reaction update.
AB  - Increasing numbers of articles on adverse drug reactions are published in a wide
      range of medical journals. To help keep you up-to-date with the latest advances
      worldwide on all aspects of adverse drug reactions, this section of the journal
      brings you information selected from the drug safety alerting service Reactions
      Weekly. The following reports are selected from the latest issues, summarizing
      the most important clinical studies, adverse reaction news, and expert opinion
      pieces published across a broad range of literature sources.

PMID- 12503259
TI  - New concepts in intensive care: dexmedetomidine and immunonutrition.

PMID- 12503260
TI  - Dexmedetomidine: a novel drug for sedation and analgesia in the ICU.

PMID- 12503261
TI  - Dexmedetomidine: a sedative-analgesic drug for the 21st century.

PMID- 12503262
TI  - Dexmedetomidine in intensive care unit: a study of hemodynamic changes.
AB  - BACKGROUND: Dexmedetomidine is a potent new alpha-2 adrenoceptor agonist with an
      alpha-2 to alpha- ratio more than 7 times that of clonidine. Its potent sedative,
      analgesic and sympatholytic effects blunt the cardiovascular responses
      (hypertension, tachycardia) without unexpected toxicity. Many reports confirmed
      its pharmacological properties if given by infusion. Recent report confirmed
      favorable non-depressant effect on respiration and blood gases. SETTING: ICU
      patients at King Khalid University Hospital. PATIENTS AND METHOD: Open label
      clinical evaluation on ten surgical patient ASA I class received dexmeditomidine
      infusion to the sedative effect level of Ramsy scale of 3 for ventilated patients
      and 2 for spontaneously breathing patient. The clinical observation and analgesic
      requirement as well as the hemodynamic parameters and hemoglobin oxygen
      saturation were observed for the period of ventilation and weaning till discharge
      from the ICU. These records were subjected to paired t test for values measured
      at preinfusion period compared to 10 minutes and 6 hours measurement after
      infusion. RESULTS: The study confirmed the previous findings of previous reports
      regarding the cardiovascular stability and non depressive effect on respiration.
      It also confirmed the sparing effect on the use of analgesics which indicates its
      analgesic effect. The sedation quality is unique in that the patient is easily
      arousable. This was reported favorably by the nursing staff. Bradycardia was
      observed in one patient who was treated effectively by stopping the infusion.
      CONCLUSION: We concluded that dexmedetomidine is useful sedative agent with
      analgesic properties which reduce the analgesic requirement of the patient. The
      patient were ventilated, weaned, then breathed spontaneously in a satisfactory
      manner.

PMID- 12503263
TI  - Phase III study on dexmedetomidine used for postoperative sedation of patients
      requiring mechanical ventilation for less than 24 hours: the French experience.

PMID- 12503264
TI  - Issues of nutrition and immunonutrition in the intensive care.

PMID- 12503265
TI  - [Various immunological aspects of ulcer formation (a literature review)].
AB  - The duodenal ulcerative disease is accompanied by increase of blood serum
      interleukins, that is manifested not by only local, but also by common response
      of organism to damage. It is evidence of activation of T- and B-lymphocytes,
      endothelial and epithelial cells, of stimulation of apoptosis processes, of
      cellular differentiation and proliferation playing the important role in
      regeneration of duodenal mucous membrane. Therefore the definition of interleukin
      profile for ulcerative disease can have a prognostic value, as it allows to
      receive additional information regarding to activity of disease, its prognosis
      and respectively to efficiency of treatment.

PMID- 12503266
TI  - [Microcirculation in patients with chronic gastritis depending on its
      exacerbation severity and morphological type].
AB  - The study of microvasculature in bioptic specimens of gastric mucosa and of
      conjunctival microcirculation from 254 patients with chronic gastritis revealed
      that exacerbation of the disease proceeds with severe disorders of terminal blood
      flow which are typical for the chronic relapse trombohemorrhagic syndrome and
      have generalized character. The microvascular disorders is manifested by plasma-
      and hemorrhages, by microvascular spasm and dilatation, intravascular hemostasis
      and microthrombosis. These manifestations were more expressed over the period of
      bright marked exacerbation of the disease and in patients with erosive affection
      of gastric mucosa.

PMID- 12503267
TI  - [Treatment arterial hypertension by beta-adrenergic blockers in elderly patients
      with gastrointestinal disorders].
AB  - Beta-adrenergic blocking agents are applied successfully in patients with
      arterial hypertension and ischemic heart disease not only in cardiology but also
      in gastroenterology.

PMID- 12503268
TI  - [Duspatalin in functional disorders of the Oddi's sphincter in patients subjected
      cholecystectomy].
AB  - There was an examination of 20 patients who had cholecystectomy and have
      dysfunctional disorders of the Oddi's sphincter. All of the patients underwent
      the monotherapy with Mebeverine Retard in the dosage of 200 mg twice a day. The
      treatment efficiency was evaluated by the dynamics of clinical symptoms, results
      of the study of biochemical blood indices, data of the ultrasonic examination,
      and intragastric pH measurement. A positive dynamics was observed against the
      background of the preparation administration, and it became apparent from the
      disappearance or reduction of pains strength, dyspeptic manifestations,
      normalization or improvement of biochemical blood indices, and reduction of the
      common bile duct lumen width according to the ultrasonic examination data.

PMID- 12503269
TI  - [Esophageal epithelial cells renewal in evaluation of the pariet efficacy in the
      treatment of patients with reflux esophagitis].
AB  - The article provides the data on 20 patients with erosive reflux esophagitis, who
      were treated with Pariet (rabeprazole). It was shown on the basis of conducted
      clinical endoscopic, morphological and immunohistochemical studies that the
      application of Pariet in treatment of patients with erosive esophagitis
      contributes to clinical endoscopic remission, regression of inflammatory changes,
      recovery of apoptosis processes and proliferative activity of esophagus
      epithelial cells within a shorter period of time. The results of the observation
      allow recommending Pariet as a highly efficient preparation for treatment of
      patients with gastroesophageal reflux disease.

PMID- 12503270
TI  - [Treatment of patients with ulcer at an outpatient facility].
AB  - The most frequent affection of digestive apparatus is the ulcerative disease.
      Ulcerative duodenal or gastric affection irrespective of its localization is a
      chronic cyclic recidivating disease of whole organism. It affects mainly an
      active able-bodied age and often results in heavy course and physical disability.
      The complicated forms of ulcerative disease--bleeding, perforation, stenosis-
      require the surgical intervention.

PMID- 12503271
TI  - [Efficacy of gastrosidine (famotidine) in the treatment of gastroesophageal
      reflux at the reflux esophagitis stage].
AB  - There is a disclosure of the results of the therapy of gastroesophageal reflux
      disease at the stage of reflux esophagitis with gastrosidin (famotidine), 40 mg
      twice a day during 4-8 weeks. The dosage of gastrosidin (famotidine) was reduced
      to 40 mg a day only if side effects appeared: diarrhea (4) and urticaria (3).
      After four weeks of treatment, endoscopic symptoms of esophagitis disappeared in
      17 patients out of 28 (60.7%), and a positive dynamics was recorded in 11
      patients. After eight weeks of treatment, the disappearance of endoscopic
      symptoms of esophagitis was recorded in 7 patients out of 8 (including the
      healing of the peptic esophagus ulcer in one patient). Three patients (who were
      feeling good) refused to undergo a control endoscopic examination.

PMID- 12503272
TI  - [Acid-forming stomach function and characteristics of reflux disorders in
      patients with bile stone disease and duodenal ulcer combination].
AB  - Results of examination of patients suffering from cholecystitis combined with
      duodenal ulcerative disease and accompanying duodenogastric reflux are presented.
      The comparison of acidifiable gastric function state in patients suffering from
      cholelithiasis combined with duodenal ulcerative disease and patients with only
      cholecystitis or duodenal ulcerative disease was performed. Intragastric pH-metry
      allows not only to study acidifiable gastric function but also to reveal
      functional disorders like duodenogastric reflux. Expressed and resistant
      duodenogastric reflux can result in structural modification of gastric mucosa.

PMID- 12503273
TI  - [A case of the successful treatment of the esophageal leukoplakia with
      rabeprazole].
AB  - This clinical endoscopic study is of interest because clinical and endoscopic
      remission of the disease with a torpid course was achieved in a patient with
      gastroesophageal reflux disease with a continuously recurrent course complicated
      with leukoplakia under the condition of regular combination of preparations of
      the base course PPIs (Pariet) + prokinetic agent (Motilium) + antacid
      (Magalphil), conduction of continuous treatment during 12 weeks and subsequent
      supporting therapy (Pariet, 20 mg) during 6 months in the weekend treatment mode,
      as well as adherence to recommendations for changing the lifestyle.

PMID- 12503274
TI  - [Acid-base blood balance in patients with ulcer under treatment by the gastric
      secretion inhibitors and antacids].
AB  - There was an analysis of the results of the study of intragastric acidity and
      acid-base balance (ABB) of the blood in 25 patients with duodenal ulcer. The
      patients were examined before and against the background of the 14-day
      monotherapy with one of the following preparations: Losec, 40 mg (omeprazole),
      famotidine, 80 mg (Quamatel), Phosphalugel, or placebo.

PMID- 12503275
TI  - [Conservative treatment of patients with stomach polyps].
AB  - The estimation of therapeutic efficiency of combined application of Ranitidin,
      Amoxicillin and Metronidazole in 100 patients with gastric polyposis is carried
      out. It is shown, that a painful syndrome and dyspeptic manifestations are
      liquidated or diminish under treatment influence. Simultaneously some favorable
      shifts on the part of gastric function is marked. According to the data of long
      term observations in the majority of the patients the disappearance of polyps or
      decrease of their sizes is marked.

PMID- 12503276
TI  - [Use of Panzytrat in the replacement therapy of exocrine pancreatic insufficiency
      (an analytical review)].
AB  - The development of new drug formulations of pancreatine based on the principle of
      microdosage with a pH-sensitive coating produced the most demonstrative clinical
      result--a considerable increase in duration and quality of life of patients with
      chronic pancreatitis and cystofibrosis, most of which are children. Clinical
      studies confirmed high efficiency and safety of Panzytrat in open and double
      blind comparative clinical studies with the participation of 4,557 patients with
      chronic pancreatitis, mucoviscidosis, and pancreathogenous digestion disorders.
      In addition to the above-mentioned symptoms, indications for application of
      Panzytrat also include any clinical symptoms of the pancreas relative excretory
      insufficiency, in particular, states after oncological diseases and surgical
      operations (obstruction of ducts, resection, cholecystectomy, etc.) up to a
      failure to adhere to a diet and overeating.

PMID- 12503277
TI  - [A status of the adaptational region of the autonomic nervous system in children
      with chronic gastroduodenitis living under ecologically unfavorable conditions].
AB  - The authors carry out the analysis of adaptation disorders of a link of
      vegetative of nervous system at children with chronic gastroduodenitis, living
      under poor ecological conditions. It is shown, that in these patients the power
      of vagus connections with vegetal nervous system prevails. In loading test, the
      inadequacy of adaptation comes to light. The accumulation of Mn and Cr in the
      blood serum is accompanied by high power of sympathetic connections with vegetal
      nervous system and accumulation of Ph in the blood serum--by high power of
      parasympathetic connections with vegetal nervous system.

PMID- 12503278
TI  - [Comparative experimental enzymatic activity and clinical efficacy of pepsin K
      and abomin].
AB  - Hen pepsin (pepsin K) in the experiment on proteolytic activity of hemoglobin
      surpasses porcine pepsin (abomin) with pH of medium 2 in 1.7 times, with pH of
      medium 3 in 44 times, that makes it more acceptable for treatment of enzymatic
      insufficiency of stomach. In the clinic reception of pepsin K in tablets for 4
      weeks had a positive effect for all 10 patients after the surgical intervention
      on the stomach. The results were good for seven of them, and satisfactory for
      three patients.

PMID- 12503279
TI  - [Interrelations of the pancreas exocrine and endocrine functions in chronic
      alcohol pancreatitis].
AB  - In order to achieve a positive therapeutic effect in case of secondary pancreatic
      diabetes in patients with chronic pancreatitis, it is necessary to conduct
      conservative therapy aimed at parallel correction of the excretory and incretory
      functions of the pancreas.

PMID- 12503280
TI  - [Pharmacoeconomic aspects of the 1-week eradication treatment of duodenal ulcer
      associated with Helicobacter pylori].
AB  - There is a disclosure of the results of one-week eradication therapy
      (esomeprazole, 20 mg + Flemoxin Solutab, 1,000 mg + Clarithromycin, 500 mg, twice
      a day) without any subsequent antisecretory therapy. In order to control the
      healing of non-complicated ulcers of the duodenal bulb, the first control
      endoscopy (esophagogastroduodenoscopy) was conducted after 7 days, and the second
      one was conducted 4 weeks after the termination of patients' treatment. The
      healing of ulcers of the duodenal bulb was recorded in 89.5% and 89.5% of cases,
      respectively. A control determination of the H. pylori semination of the mucous
      coating of stomach was accomplished 4 weeks after the termination of patients'
      treatment. According to the data of the fast urease test and 13C-urease
      respiratory test, the HP eradication was recorded in all of the patients (100%),
      and according to the data of the histologic method of target biopsy materials
      studies, it was recorded in 94.7% of cases. A pharmacoeconomic analysis of the
      acquired data showed that the seven-day eradication therapy of non-complicated
      duodenal ulcer, where esomeprazole was used as the basic preparation, is most
      efficient and most economically expedient.

PMID- 12503281
TI  - [Hemorrhagic shock. A new concept of endoscopic hemostasis and prospects of the
      non-surgical treatment of ulcer and gastroduodenal hemorrhages complicated by
      hemorrhagic shock].
AB  - A new direction with the use of endoscopic hemostasis (EH) was offered in the
      complex program of metabolic rehabilitation of patients with ulcerous
      gastroduodenal bleedings (UGDB) and hemorrhagic shock (HS). There was a study of
      the results of treatment of 44 patients (29 men and 15 women at the age from 61
      to 77) with severe concurrent diseases and UGDB complicated with HS. Recurrences
      of UGDB in case of HS are a factor of high operative-anesthetic risk. Endoscopic
      preventive metabolic hemostasis is a prospective direction in rehabilitation of
      patients with UGDB complicated with HS. It is necessary to improve the EH methods
      for treatment of continued arterial bleedings from giant gastroduodenal ulcers.

PMID- 12503282
TI  - [Therapeutic and diagnostic tactics in complication of ulcer disease in elderly
      and aged].
AB  - In 78% of cases the ulcerative disease in elderly age proceeds with complications
      and presents a serious surgical problem. The specificity of elderly patients is
      the combination of several pathologies, on background of which the ulcerative
      disease proceeds. The level of an expressiveness of accompanying pathology
      influences on the prognosis of disease course and on the choice of medical
      tactics. Therefore for objectivization of state heaviness of the patient group
      mark systems of an estimation MODS and APACHE III are used. The interventions in
      gastroduodenal bleedings for the patients of elderly age should be differentiated
      and depended on a risk degree of bleeding relapse and adequate estimation of MODS
      heaviness. In 55.4% of the elderly patients the ulcerative perforation occur
      without antecedent history. Therefore indications to sewing of ulcers, including
      little-invasive interventions, should be extended in this group of the patients.
      The size of radical surgical interventions in absence of manifestation of the
      polyorganic insufficiency for the elderly patients should be the same, as for the
      younger patients.

PMID- 12503283
TI  - [Lipid metabolism in diseases associated with malabsorption syndrome].
AB  - The review is devoted to lipid metabolism in diseases related to their
      malabsorption, such as a celiacia, chronic enteritis, calculous cholecystitis and
      others. The problems on involvement of lipid fractions in development of
      malabsorption processes are discussed.

PMID- 12503284
TI  - [Chronic diarrhea: pathogenesis and therapy].
AB  - Periodical diarrhea is one of the steadiest symptoms of chronic bowels diseases.
      This term defines an increase of stool frequency (over three times a day) with
      the excretion of greater amount and more liquid consistency of excrements as
      compared to usual bowels emptying of the given individual. Diarrhea is considered
      to be chronic if its duration is over 30 days. Pathogenetic mechanisms of
      formation and development of chronic diarrheas have a lot in common. As a result,
      any diarrhea is a clinical manifestation of a disorder of water and electrolytes
      transportation in the digestive tract. Such disorders appear due to indigestion,
      absorption and secretion disorders. At that the small intestine and large
      intestine should be considered as a single physiological unit.

PMID- 12503285
TI  - [General variable hypogammaglobulinemia].
AB  - The purpose of the paper was studying the features of course and treatment of
      common variable hypogammaglobulinemia (CVHG), proceeding with intestinal function
      disorders functions.

PMID- 12503286
TI  - [Hemorrhoids].
AB  - Hemorrhoids is believed by right to be one of the most widely spread human
      sufferings ranking first among diseases of the rectum and large intestine.
      According to the data of numerous studies devoted to this problem, from 2.9 to
      27.9%% of population of different countries suffer from hemorrhoids. Most authors
      agree that men suffer from hemorrhoids more often than women do and that its
      frequency increases with the aging. For the sake of justice, it is necessary to
      note that some researchers insist that men and women suffer from this disease
      equally often but that men ask for medical care 1.5 times more often.

PMID- 12503287
TI  - [Ultrasound transabdominal study of the gastrointestinal tract].
AB  - It has been conventionally believed for a long time that echography of the
      intestines and other hollow organs containing gas could give very little
      information and would be even impossible at times due to the acoustic noise
      created by the gas medium in their lumen. Nevertheless, it is high time to
      elaborate new methodological approaches to diagnostics of these diseases and
      assessment of efficiency of the conducted therapy due to the wide spread of
      gastrointestinal tract diseases, complexity of their pathogenesis, insufficient
      effectiveness of the current methods of treatment, and the inclination to the
      prolonged recurrent course.

PMID- 12503288
TI  - [Significance of the operational test parameters in selection of a diagnostic
      test for Helicobacter infection].
AB  - The group of 89 patients was examined, 63 of them suffered by a duodenal
      ulcerative disease, 11--by gastric ulcerative disease and 15--by chronic
      gastritis. It was conducted the comparison of the following indices: sensitivity,
      specificity, relationship of probability and diagnostic efficiency of
      histological, cytological methods, urease and respiratory tests, method of
      polymerase chain reaction, qualitative and quantitative definition of antibodies
      of the class IgG in serum blood to H. pylori by a method of enzyme immunoassay
      and Western-blot for H. pylori infection diagnostics was carried out. The results
      show that in choice of a diagnostic method of infection H. pylori it is better to
      use such characteristics as sensitivity and specificity, which more objectively
      reflect the diagnostic possibilities of each test.

PMID- 12503289
TI  - [Study of the glycosaminoglycan-glycosaminoglycan hydrolase system for evaluation
      of the healing dynamics in stomach and duodenal ulcer].
AB  - When studying the state of metabolism of the main substance of the connective
      tissue (glycosaminoglycan (GAG) and one of gag-hydrolases) in case of stomach and
      duodenal ulcers in patients under in-patient clinic conditions, it was shown that
      the amount of GAG in the urine approximately doubles in both groups in the state
      of exacerbation, and the given index reduces to the norm in the state of
      remission with a insignificant fluctuation of the b-glucuronidase level in the
      blood serum.

PMID- 12503290
TI  - [Morphological characteristics of colon polyps].
AB  - The most widespread method of removal of the polyps was polypectomy through
      colonoscope with electrocoagulation of polyp leg or basis. The survey
      morphological study of 123 bioptates, received from the patients with polyposis,
      was carried out. For histological study of bioptates, preparations were painted
      with hematoxylin and cosine. It was determined, that adenomatous polyps were
      revealed in 66.7 +/- 4.2% of cases, fibrous polyps in 3.3 +/- 1.6% of cases. The
      results of comparative research of adenomatous polyps have shown, that common
      tubular polyps were revealed much more onen among adenomatous polyps--in 74.4 +/-
      4.8% of cases. Tubular-papillar-villiferous polyps are revealed only in 25.6 +/-
      4.8% of cases. Tubular polyps in the majority of cases (62 5.3%) had the
      expressed degree of dysplasia. The received data correspond the literary data,
      which shows that glandular T)olvDS concern to the most eood-cmalitv colonal
      tumours.

PMID- 12503291
TI  - [Telemedicine and law: the interaction dynamics].
AB  - The problem of development of legal base has arisen last years on a wave of
      active introduction of telemedical technologies and disputes on legal regulation
      the Internet. May 20, 2002 carried out parliamentary hearings "About telemedicine
      and information policy in sphere of protection of health of the citizens of
      Russian Federation". The basic themes of statements were experience of use of
      telemedical technologies, legal problems at rendering telemedical services,
      necessity of formation of the State target program on telemedicine.

PMID- 12503292
TI  - Market study shows capitation down but not out.

PMID- 12503293
TI  - Lawsuits against Medicaid programs may boost capitation rates.
AB  - A legal victory in Colorado over inadequate Medicaid capitation rates and a
      similar lawsuit field in Oregon may lead to improved managed care reimbursement
      rates for health plans and providers.

PMID- 12503294
TI  - South Carolina providers succeed with Medicaid risk plans.
AB  - Capitating Medicaid patients in many states can be a money-losing proposition for
      physician groups and hospitals, especially after more than a dozen states cut
      reimbursement rates this year and more plan changes in 2003. But Medicaid
      capitation in South Carolina appears to work. Here's why.

PMID- 12503295
TI  - AMGA survey shows medical group profits are on the slide.
AB  - Holding down increases in physician and nurse compensation and improved
      management of human resource costs helped capitated providers in the Eastern
      region improve per physician median profits to $1,686 in 2001 from a median loss
      of $767 in 2000, according to the 2002 financial operations survey from the
      American Medical Group Association. Find out what the successful groups have in
      common.

PMID- 12503296
TI  - Caspase-3 colorimetric assay.

PMID- 12503297
TI  - Maintaining GFP tissue fluorescence through bone decalcification and long-term
      storage.

PMID- 12503298
TI  - Vital stain to study cell invasion in modified Boyden chamber assay.

PMID- 12503299
TI  - Enhanced efficiency of pSV1-RecA-based BAC recombineering.

PMID- 12503300
TI  - Single-tube nested PCR using immobilized internal primers.

PMID- 12503301
TI  - PCR-based method for identification of integration events in the Pichia pastoris
      genome.

PMID- 12503302
TI  - Mammalian expression vectors for epitope tag fusion proteins that are toxic in E.
      coli.

PMID- 12503303
TI  - Microscale assay for screening of inhibitory activity of Lactobacillus.

PMID- 12503304
TI  - High-quality genomic DNA from human whole blood and mononuclear cells.

PMID- 12503305
TI  - Isolation of genomic DNA from human whole blood.

PMID- 12503306
TI  - Promoterless luciferase reporter gene is transactivated by basic helix-loop-helix
      transcription factors.

PMID- 12503307
TI  - pRL-TK induction can cause misinterpretation of gene promoter activity.

PMID- 12503308
TI  - Targeting the kinesin Eg5 to monitor siRNA transfection in mammalian cells.
AB  - RNA interference, the inhibition of gene expression by double-stranded RNA,
      provides a powerful tool for functional studies once the sequence of a gene is
      known. In most mammalian cells, only short molecules can be used because long
      ones induce the interferon pathway. With the identification of a proper target
      sequence, the penetration of the oligonucleotides constitutes the most serious
      limitation in the application of this technique. Here we show that a small
      interfering RNA (siRNA) targeting the mRNA of the kinesin Eg5 induces a rapid
      mitotic arrest and provides a convenient assay for the optimization of siRNA
      transfection. Thus, dose responses can be established for different transfection
      techniques, highlighting the great differences in response to transfection
      techniques of various cell types. We report that the calcium phosphate
      precipitation technique can be an efficient and cost-effective alternative to
      Oligofectamine in some adherent cells, while electroporation can be efficient for
      some cells growing in suspension such as hematopoietic cells and some adherent
      cells. Significantly, the optimal parameters for the electroporation of siRNA
      differ from those for plasmids, allowing the use of milder conditions that induce
      less cell toxicity. In summary, a single siRNA leading to an easily assayed
      phenotype can be used to monitor the transfection of siRNA into any type of
      proliferating cells of both human and murine origin.

PMID- 12503309
TI  - Noninvasive fluorescent imaging reliably estimates biomass in vivo.
AB  - Whole-body optical imaging of small animals has emerged as a powerful, user
      friendly, and high-throughput tool for assaying molecular and cellular processes
      as they occur in vivo. As with any imaging method, the utility of such technology
      relies on its ability to provide quantitative, biologically meaningful
      information about the physiologic or pathologic process of interest. Here we used
      an animal tumor model to evaluate the extent of correlation between noninvasively
      measured fluorescence and more traditional measurements of biomass (tumor volume
      and tumor weight). C57/BL6 mice were injected subcutaneously with murine colon
      adenocarcinoma cells that were engineered to express GFP. Serial measurements of
      fluorescence intensities were performed with a macroscopic in vivo fluorescence
      system. The progressive increases in intensity correlated strongly with growth in
      tumor volume, as determined by caliper measurements (R2 = 0.99). A more stringent
      correlation was found between fluorescence intensity and tumor weight (R2 = 0.97)
      than between volume and weight (R2 = 0.89). In a treatment experiment using tumor
      necrosis factor-alpha, fluorescence intensity (but not tumor volume) was able to
      differentiate between treated and control groups on day 1 post-treatment. These
      results validate the ability of noninvasive fluorescent imaging to quantify the
      number of viable, fluorescent cells in vivo.

PMID- 12503310
TI  - Purification of histidine-tagged T4 RNA ligase from E. coli.
AB  - Here we report the construction of a histidine-tagged T4 RNA ligase expression
      plasmid (pRHT4). The construct, when overexpressed in BL21 (DE3) cells, allows
      the preparation of large quantities of T4 RNA ligase in high purity using only a
      single purification column. The histidine affinity tag does not inhibit enzyme
      function, and we were able to purify 1-3 mg pure protein/g cell pellet. A simple
      purification procedure ensures that the enzyme is de-adenylated to levels
      comparable to those found for many commercial preparations. The purified protein
      has very low levels of RNase contamination and functioned normally in a variety
      of activity assays.

PMID- 12503311
TI  - Analysis of multidimensional biological image data.

PMID- 12503312
TI  - Identification of nitric oxide synthase neurons for laser capture microdissection
      and mRNA quantification.
AB  - An immunohistochemical technique was developed to visualize nitric oxide synthase
      (NOS)-immunopositive neurons in fresh-frozen tissue sections of rat brain for
      laser capture microdissection (LCM) and mRNA analysis. The effect of tissue
      fixation and the choice of fluorophore were investigated. Here we describe a
      rapid immunofluorescence protocol that allows the processing of fresh-frozen
      tissue sections within eight minutes and subsequent mRNA extraction and real-time
      PCR from pools of 20 NOS-immunopositive LCM neurons. The cellular complement of a
      subset of ionotropic glutamate receptors, specifically N-methyl-D-aspartate
      receptor subunit mRNAs, was examined because these receptor complexes are thought
      to mediate the effects of fast and slow glutamate excitotoxicity. Real-time PCR
      data revealed that striatal NOS interneurons express the mRNAs encoding NR1,
      NR2A, NR2B, and NR2D but not NR2C. These LCM mRNA data are consistent with
      previous in situ hybridization studies and demonstrate the utility of rapid
      immuno-LCM with real-time quantitative PCR for the study of mRNA abundance in
      discrete populations of neurons within the mammalian brain.

PMID- 12503313
TI  - Marker for real-time analysis of caspase activity in intact cells.
AB  - Apoptosis, or programmed cell death, is an important regulator of growth,
      development, defense, and homeostasis in multicellular organisms. A family of
      cysteine proteases known as caspases is central to many apoptotic pathways, and
      thus detection of their activity offers an effective means to assess apoptosis.
      However, currently available methods only allow the evaluation of in vivo caspase
      activity at a given time point or over a few hours. To assess the activity over
      extended periods of time, we designed a novel, real-time, in vivo marker that
      utilizes the N-end rule degradation pathway to allow the detection of caspase
      activity as reflected by increasing enhanced GFP (EGFP) stability. The marker has
      an N-terminal arginine in the absence of caspase activity and is rapidly
      degraded. In vivo caspase activity removes the marker's N-terminal arginine
      residue, leaving an EGFP with an N-terminal methionine that results in stable
      fluorescence. In our study, the marker accurately depicted an increase in caspase
      activity in apoptotic cells and also detected significant endogenous caspase
      activity in non-apoptotic cells. The downstream effects of this endogenous
      activity detected in intact, nonapoptotic cells must be regulated by the cell
      preventing apoptosis. These studies also demonstrate the feasibility of using the
      N-end rule to study endogenous enzymatic activities other than those associated
      with proteasomal degradation.

PMID- 12503314
TI  - Direct detection of protein thiol derivatization by PAGE.

PMID- 12503315
TI  - Buffered non-fermenter system for lab-scale production of secreted recombinant
      His-tagged proteins in Saccharomyces cerevisiae.
AB  - Expression of recombinant proteins using a secretion system can minimize co
      purification of contaminating host proteins. Production of His-tagged recombinant
      proteins in the yeast alpha-factor secretion system has previously required a
      fermenter system to control the growth conditions such as pH of the yeast
      culture. We describe an inexpensive non-fermenter system for the production of
      secreted recombinant His-tagged proteins in Saccharomyces cerevisiae that uses a
      buffered low peptone YP glycerol medium, which does not interfere with
      immobilized metal affinity chromatography. Maspin, a tumor suppressor serpin, was
      expressed as a secreted N-terminal His/FLAG-tagged protein. Purification of the
      soluble active recombinant protein only requires centrifugation, concentration by
      ultrafiltration, and Ni2+ affinity chromatography. Purified protein yields of
      this system are 3-5 mg/L culture medium.

PMID- 12503316
TI  - Ink-jet printer heads for ultra-small-drop protein crystallography.
AB  - Mass-produced automated piezoelectric driven picoliter delivery systems (printer
      heads) are fast, inexpensive, and reliable devices that are capable of delivering
      a very large range of volumes and are ideally suited for high-throughput protein
      crystallography studies. We used this technology to set up under-oil
      crystallization experiments with drop sizes from the 200-nL to 3-microL volume
      range, commonly used in protein crystallography, and show its application in
      setting ultra-small (2 nL) drops, the smallest drop volume reported to date for
      this type of assay.

PMID- 12503317
TI  - Proteomic approaches for the global analysis of proteins.
AB  - Improvements in technology that allow miniaturization and high-throughput
      analyses of thousand of genes and gene products have changed the focus and scope
      of research and development in both academia and industry. It is now possible to
      study entire proteomes with the goals of elucidating protein expression,
      subcellular localization, biochemical activities, and their regulation.
      Alterations in different cell types and conditions and in normal and disease
      states can be revealed. This wealth of information not only has facilitated our
      basic understanding of many biological processes but also has enormous potential
      for drug discovery and development.

PMID- 12503318
TI  - JavaScript DNA translator: DNA-aligned protein translations.
AB  - There are many instances in molecular biology when it is necessary to identify
      ORFs in a DNA sequence. While programs exist for displaying protein translations
      in multiple ORFs in alignment with a DNA sequence, they are often expensive,
      exist as add-ons to software that must be purchased, or are only compatible with
      a particular operating system. JavaScript DNA Translator is a shareware
      application written in JavaScript, a scripting language interpreted by the
      Netscape Communicator and Internet Explorer Web browsers, which makes it
      compatible with several different operating systems. While the program uses a
      familiar Web page interface, it requires no connection to the Internet since
      calculations are performed on the user's own computer. The program analyzes one
      or multiple DNA sequences and generates translations in up to six reading frames
      aligned to a DNA sequence, in addition to displaying translations as separate
      sequences in FASTA format. ORFs within a reading frame can also be displayed as
      separate sequences. Flexible formatting options are provided, including the
      ability to hide ORFs below a minimum size specified by the user. The program is
      available free of charge at the BioTechniques Software Library
      (www.Biotechniques.com).

PMID- 12503319
TI  - Restriction enzyme recognition sequence search program.
AB  - A critical and difficult part of characterizing restriction enzymes and
      methylases is the identification of recognition sequences. To simplify this
      process, we have developed a plasmid transformation method along with a computer
      program named RM search that determines the exact recognition sequences for given
      restriction and modification systems.

PMID- 12503320
TI  - Express primer tool for high-throughput gene cloning and expression.
AB  - High-throughput approaches for gene cloning and expression require the
      development of new nonstandard tools for molecular biologists and biochemists. We
      introduce a Web-based tool to design primers specifically for the generation of
      expression clones for both laboratory-scale and high-throughput projects. The
      application is designed not only to allow the user complete flexibility to
      specify primer design parameters but also to minimize the amount of manual
      intervention needed to generate a large number of primers for the simultaneous
      amplification of multiple target genes.

PMID- 12503321
TI  - Genome-tools: a flexible package for genome sequence analysis.
AB  - Genome-tools is a Perl module, a set of programs, and a user interface that
      facilitates access to genome sequence information. The package is flexible,
      extensible, and designed to be accessible and useful to both nonprogrammers and
      programmers. Any relatively well-annotated genome available with standard GenBank
      genome files may be used with genome-tools. A simple Web-based front end permits
      searching any available genome with an intuitive interface. Flexible design
      choices also make it simple to handle revised versions of genome annotation files
      as they change. In addition, programmers can develop cross-genomic tools and
      analyses with minimal additional overhead by combining genome-tools modules with
      newly written modules. Genome-tools runs on any computer platform for which Perl
      is available, including Unix, Microsoft Windows, and Mac OS. By simplifying the
      access to large amounts of genomic data, genome-tools may be especially useful
      for molecular biologists looking at newly sequenced genomes, for which few
      informatics tools are available. The genome-tools Web interface is accessible at
      http://genome-tools.sourceforge.net, and the source code is available at
      http://sourceforge.net/projects/genome-tools.

PMID- 12503322
TI  - Software for machine-independent quantitative interpretation of SSCP in capillary
      array electrophoresis (QUISCA).
AB  - PCR single-stranded conformational polymorphism (SSCP) analysis is a simple and
      rapid electrophoretic technique for the sensitive detection of sequence variants
      of PCR products. Here we describe a cross-platform program package, quantitative
      interpretation of SSCP in capillary array (QUISCA), which allows semi-automated
      quantitative detection of sequence variants separated by multicolor fluorescence
      based SSCP electrophoresis using various capillary array apparatus. The program,
      together with the QUISCAview as a graphical user interface, takes trace data in
      ASCII format and processes them with three modules: signal denoising/baseline
      subtraction, color-matrix construction/application, and calibration of peak
      positions between multiple capillary runs using internal standard peaks. QUISCA
      is compatible with data from various widely used capillary array sequencers and
      is suitable not only for finding or typing SNPs in individual DNAs but also for
      the accurate estimation of the allele frequencies of many SNPs using a pooled DNA
      strategy. QUISCA can also serve as a versatile core program for various fragment
      analyses.

PMID- 12503323
TI  - Small-scale telomere repeat sequence content assay using pyrophosphorolysis
      coupled with ATP detection.
AB  - Studies of telomere length have been carried out in diverse areas of research.
      However, current methods to measure telomeres are cumbersome and not amenable to
      high-throughput analyses. Using a coupled pyrophosphorolysis/trans
      phosphorylation reaction, we have developed a novel assay to quantitate telomere
      sequence content in a single tube or 96-well format. The method uses a telomere
      specific oligonucleotide probe to sample nanogram quantities of DNA without PCR
      amplification. Polymerase and kinase enzymes drive the production of ATP, which
      is then monitored with a luciferase enzyme reporter system. Using this approach,
      we demonstrated that the luminescent output was linear across a 100-fold range of
      DNA input, and the assay was sensitive to 0.4-1 ng DNA. A control probe reaction
      and a DNA quantitation reaction were also designed using the same
      pyrophosphorolysis technology to correct for background activity and normalize
      the signal against variations in DNA input, respectively. Finally, we show that
      the normalized luminescent signal generated by this new method is highly
      correlated to the telomere restriction fragment length for six human cell lines.

PMID- 12503324
TI  - Development of a chemiluminescence-based ribonuclease protection assay.
AB  - The ribonuclease protection assay (RPA) is a widely used method for the detection
      and quantification of specific mRNA transcripts in a complex mixture of total RNA
      or mRNA molecules. While exhibiting many advantages over other RNA detection
      methods, RPAs are traditionally performed using radiolabeled probes that often
      require gel purification steps and lengthy exposure times to visualize results.
      Moreover, these probes can only be used for 1-2 weeks because of their short
      isotopic half-life and radiolysis. We report a method that improves the
      traditional RPA by replacing radiolabeled probes with biotinylated probes and
      lengthy exposure times with quick, streptavidin/HRP-based chemiluminescent
      detection technology. Biotinylated probes can be used without get purification
      and are stable for years, as opposed to weeks. Most importantly, our
      streptavidin/HRP-based chemiluminescent technology enables us to achieve
      sensitivity results similar to radioactive RPAs and to detect multiple
      transcripts in a single sample more efficiently. Furthermore, this new protocol
      addresses and eliminates the one major drawback unique to using biotinylated
      probes in chemiluminescent RPAs: a confounding artifact, not seen when running
      radioactive RPAs but commonly detected when using certain biotinylated rare
      message probes.

PMID- 12503325
TI  - Social security reform: a worldwide phenomenon.

PMID- 12503326
TI  - Social security reform in Latin America: policy challenges.
AB  - Over the last decade Latin American countries have served as the world's
      laboratory for pension systems based on individual retirement savings accounts.
      Some countries have adopted defined-contribution individual accounts as a
      replacement for state-run pension systems; other countries have embraced mixed
      systems of have made individual accounts optional and supplementary. This article
      outlines some of the most significant elements of recent Latin American pension
      reforms and examines some of the most serious policy challenges faced by
      governments implementing the new systems of individual accounts, including the
      need to reduce administrative costs, limit evasion, incorporate new categories of
      workers into the system, and improve competition in the pension fund industry.
      The authors conclude that there is no single Latin America model, and that reform
      itself has been and will continue to be an incremental process.

PMID- 12503327
TI  - Contracting-out in the United Kingdom: a partnership between social security and
      private pension plans.
AB  - Contracting-out was introduced in the United Kingdom in 1978 as part of the
      arrangements for the State Earnings-Related Pension Scheme (SERPS) in order to
      avoid duplication with the existing well-developed defined benefit occupational
      pension plan sector. Members and sponsors of contracted-out schemes were able to
      save on their social security contributions in recognition of the fact that they
      were accruing equivalent benefits through an occupational pension plan. Later on
      this concept was extended to those with individual money purchase pension plans.
      This article considers a brief history of contracting-out, the principles of
      contracting-out, some problems associated with contracting-out, the implications
      of the introduction of stakeholder pensions and State Second Pension, and the
      latest rebate review and rebate orders. It examines how U.K. pensions policy
      since 1978 has been  based on a partnership between social security and private
      pension plans.

PMID- 12503328
TI  - Is Swedish pension reform the right medicine for aging Europe?
AB  - Following the Second World War, the idea of the life course with distinct periods
      of education, work, and retirement became popular as a result of the alliance of
      interests of unions and management, with politicians seizing the opportunity to
      accommodate them. These "social partners" implemented benefit rules and created
      practices for using old age and disability to ease the exit of older workers.
      Although justifiable at the time, now those rules and practices hinder individual
      and employer incentives to invest in human capital and work environments that
      enable older workers to remain in the workforce. The article argues that the
      workforce environment of the coming half-century, which is relevant for persons
      born around 2000, is much different from that a hundred years earlier, which
      determined the opportunities for people born around 1900. People are healthier
      and live much longer and work environments are friendlier. The article argues
      that it is no longer justifiable to subsidize exit from the workforce around the
      age of 60 for healthy workers, especially in view of the coming labor shortage in
      Europe. It also argues that the introduction of the principles of the Swedish NDC
      pension reform in Europe would provide possibilities for flexible exit from the
      workforce and remove impediments to labor mobility in Europe, which are embedded
      in many of Europe's present pension arrangements.

PMID- 12503329
TI  - Social security in Italy: towards a mixed system?
AB  - We evaluate recent reforms of Italian social security with respect to both the
      (long) transition and the new steady state, as defined by the notional defined
      contribution formula. The first is hardly sustainable in the face of the
      projected sharp increase in the dependency ratio. The second is hardly compatible
      with a good allocation of risks, given the preponderance of the pay-as-you-go
      (PAYG) component. We believe that further reforms will have to be enacted within
      PAYG (with a correction to "seniority pensions") and beyond PAYG, with the
      introduction of an opting-out clause directed at readjusting the relative weights
      of the two components in households' retirement wealth. The opting-out clause
      could be combined with TFR (severance pay) diversion, which in itself appears
      insufficient to realize such an adjustment. Recent government proposals (2001)
      are briefly discussed.

PMID- 12503330
TI  - Social security reform in the twenty-first century: the United States.
AB  - The paper reviews the history of the Social Security system in the United States
      in the twentieth century and discusses options for the twenty-first. Because of
      the steady aging of the U.S. population and the impending retirement of the large
      baby boom cohort, the Social Security program now is in long-term actuarial
      deficit. The standard twentieth century approach to this actuarial deficit would
      be to raise payroll taxes enough to pay for anticipated future benefit increases,
      but for several reasons that approach may not be so popular this time around. The
      author's preferred approach is a gradual trimming of long-term benefit growth,
      plus "add on" individual accounts to provide new saving, for the economy and for
      the retirement system. The paper also criticizes proposals for Social Security
      reform made by President Clinton and a committee appointed by President Bush,
      generally because these proposals do not provide enough new saving.

PMID- 12503331
TI  - Social security reform ideas in Japan.
AB  - Japan has a complex social security system. This article discusses the
      demographic and economic situation in Japan as background for understanding the
      setting in which the social security system functions. Japan has a three-pillar
      system for retirement income. The first pillar is the social security pension
      plan; the second pillar is the voluntary occupational pension plan; and the third
      pillar is personal savings, including the personal pension plan. The most
      important part of the retirement income system is the social security pension
      plan, which paid benefits accounting for 64% of the total income of elderly
      households in 1998. The five Employees' Pension Plans are established on a
      compulsory social insurance basis. Most large Japanese employers have a mandatory
      retirement age. Over 90% of all employees, including public sector ones, must
      retire from their career jobs at age 60.

PMID- 12503332
TI  - Social security in Asia and the Pacific: a brief overview.
AB  - In terms of numbers of people, the global challenges facing social security
      systems are largely Asian. Because of rapid population aging in Asia, while it
      accounted for 28% of the world's population aged 60 and older in 1985, that
      percentage will more than double to 58% in 2050. Provident funds are a prominent
      feature of retirement income systems in the region-Asia and the Pacific contain
      the majority of the world's countries with provident funds. These programs
      typically provide lump-sum benefits, and thus, do not provide annuity protection
      against outliving one's resources. Because of the influence of Confucian
      philosophy with its emphasis on family responsibility for elders, countries in
      the region have been relatively slow in developing social security programs.
      China does not have a social security program for workers who do not work for the
      government or in government-owned enterprises.

PMID- 12503333
TI  - Social security in Africa: a brief review.
AB  - Africa is the poorest region of the world and has the youngest and least
      developed social security programs. Most Africans are not covered by social
      security programs. The high prevalence of HIV/AIDS in some sub-Saharan countries
      and internal armed conflicts in others have created difficult problems in some
      countries for social security programs. As a result, some countries do not have
      functioning social security programs. The social security programs that do exist
      in Africa are influenced by their colonial heritage, with the programs in English
      speaking Africa differing from those in French-speaking Africa. Six different
      patterns of social security provision can be identified.

PMID- 12503334
TI  - Social security in the Middle East: a brief review.
AB  - The countries of the Middle East all have traditional social insurance type
      social security programs. The move towards defined contribution individual
      accounts that is occurring in some regions has not affected this region The
      social security programs in the Middle East are not facing the problems of
      financing found in Europe and North America, in part because they still have
      relatively high fertility rates and are thus little affected by population aging.
      They tend to have low retirement ages and some of the wealthy countries of the
      region provide very generous benefits. Many of them need to consider reforms that
      raise retirement ages. A characteristic of many of the social security old-age
      benefit programs of the region is that they exclude foreign workers, who in some
      countries account for more than half the workforce.

PMID- 12503335
TI  - Medicare outpatient payment system undergoes change.

PMID- 12503336
TI  - Aspirin use after bypass surgery may save lives.

PMID- 12503337
TI  - IOM calls for coordination of federal health care programs.

PMID- 12503338
TI  - Classifying drug-related problems in home care.

PMID- 12503339
TI  - Transforming the U.S. health care system.

PMID- 12503340
TI  - Linezolid: an oxazolidinone antimicrobial agent.
AB  - The pharmacology, antimicrobial activity, pharmacokinetics, clinical efficacy,
      and adverse effects of linezolid are reviewed. Linezolid, the only oxazolidinone
      antimicrobial approved for use in the United States, has significant activity
      against gram-positive bacteria, including penicillin-, cephalosporin-, and
      vancomycin-resistant species. Linezolid inhibits bacterial protein synthesis via
      binding to the 50S ribosomal subunit to prevent translation. The drug lacks cross
      resistance with other antimicrobials. Linezolid is primarily excreted renally as
      unchanged drug. The measured plasma half-life of four to five hours permits twice
      daily administration for all indicated infections. Virtually complete oral
      bioavailability allows for 1:1 conversion between the intravenous and oral dosage
      forms. Controlled comparative clinical trials demonstrate that linezolid is
      effective in the treatment of vancomycin-resistant Enterococcus faecium and
      methicillin-resistant Staphylococcus aureus (MRSA) infections, nosocomial and
      community-acquired pneumonia, and skin and skin-structure infections due to
      susceptible organisms. The recommended dosage is 600 mg i.v. or p.o. twice daily
      for all indications except uncomplicated skin and skin-structure infections (400
      mg twice daily); adjustments for mild to moderate renal or hepatic impairment are
      not necessary. Clinically important interactions with monoamine oxidase
      inhibitors have not been observed. Reversible myelosuppression has been observed
      in a few patients. Linezolid has gram-positive activity comparable to that of
      vancomycin, is effective in a variety of infections, and is well tolerated, with
      diarrhea, headache, and nausea being the most frequently reported adverse
      effects. Linezolid provides a reasonable therapeutic alternative for patients
      with vancomycin-resistant E. faecium infections and patients infected with MRSA
      who cannot tolerate vancomycin.

PMID- 12503341
TI  - Screening extemporaneously compounded intraspinal injections with the bacterial
      endotoxins test.
AB  - Development of a validated bacterial endotoxins test (BET) method for screening
      extemporaneously compounded intraspinal injections was studied. In accordance
      with compendial requirements, interference studies were conducted in injectable
      grade intraspinal medications using reagents licensed by the Food and Drug
      Administration. Positive controls were inoculated into a series of decreasing
      concentrations of each drug (range, 0.05-4 mg/mL) and tested by gel-clot and
      kinetic-turbidimetric BET methods to determine valid non-interfering
      concentrations. A simplified BET procedure was used for preparing drug samples,
      inoculating positive controls, conducting the test, and interpreting the results.
      The most robust test concentrations were < or = 0.5 mg/mL for baclofen,
      bupivacaine, clonidine, and morphine and < or = 0.1 mg/mL for hydromorphone. BET
      interference studies were also done for mixtures of morphine and baclofen,
      bupivacaine or clonidine. The mixtures were compatible when morphine was diluted
      to a concentration of < or = 0.25 mg/mL. The substantial dilution required to
      overcome test inhibition did not compromise the tests sensitivity when compared
      to the endotoxin limit for intraspinal infusions. Validated BET procedures for
      intraspinal drugs were sufficiently sensitive to assure the absence of endotoxin
      contamination.

PMID- 12503342
TI  - Stability of i.v. mycophenolate mofetil in 5% dextrose injection in polyvinyl
      chloride infusion bags.

PMID- 12503343
TI  - A pharmacy response to the Institute of Medicine's 2001 initiative on quality in
      health care.

PMID- 12503344
TI  - Dalteparin after total knee replacement.

PMID- 12503345
TI  - Alternative medicine use in a community hospital.

PMID- 12503346
TI  - Pharmacies' willingness to use expired antidotes and pharmaceutical-grade
      chemicals to prepare antidotes.

PMID- 12503348
TI  - Process improvement in monitoring temperature in medication refrigerators.

PMID- 12503347
TI  - Educational approach to reducing unnecessary use of antimicrobials.

PMID- 12503349
TI  - Patient satisfaction with a pharmacist-based medication assistance clinic.

PMID- 12503350
TI  - Degradation of methylprednisolone sodium succinate in a diluent-containing vial.

PMID- 12503351
TI  - Combined spinal epidural (CSE) analgesia is the preferred technique for labour
      pain relief.

PMID- 12503352
TI  - Spinal anaesthesia or CSE are the preferred techniques of anaesthesia for
      caesarean section in pre-eclampsia.

PMID- 12503353
TI  - Anaesthesia for non-obstetric surgery during pregnancy.
AB  - As with all anaesthesia, the fundamentals of physiology, pharmacology and
      pathology must be understood, as well as an appreciation of the effects of drugs
      on the mother and fetus when providing anaesthesia care in pregnancy.
      Hypothermic, hyperbaric, cardiac by-pass, hypotensive and other special
      techniques have been used safely in pregnancy. If these are contemplated then the
      anaesthetist should consult expert help. [A disk copy of the slides and all
      references cited in the lecture are available on request from the author].

PMID- 12503354
TI  - Pharmacological differences between men and women.

PMID- 12503355
TI  - Spinal anesthesia is the preferred technique for cesarean section in severe
      preeclampsia: proponent position.

PMID- 12503356
TI  - Resuscitation of the newly born.
AB  - International guidelines developed recommendations in the resuscitation of the
      new-born: at least one person trained in resuscitation of the newly born should
      attend every delivery. A minority of the new-borns require active resuscitation
      to achieve regular respiration, heart rhythm above 100/min, pink colour and
      adequate tone. Establishment of adequate ventilation should be of primary
      concern. Most new-borns who require positive-pressure ventilation can be
      adequately ventilated with a bag and mask. All healthcare providers, who may be
      asked to deal with an emergency delivery, should master such technique. In case
      of meconium-stained amniotic fluid, thorough oropharyngeal suctioning should be
      perform before the delivery of the chest. Tracheal aspiration of mecomium should
      be perform only in depressed child. Very few infants require chest compressions
      and much less administration of drugs. Umbilical access remains the most widely
      recommended access in new-born. Adequate transfer to Neonatal Unit improves
      outcome.

PMID- 12503357
TI  - Women in anaesthesia. Like a fish out of water.

PMID- 12503358
TI  - The female coronary patient.

PMID- 12503359
TI  - Heart disease in pregnancy.

PMID- 12503360
TI  - Pregnant operating room personnel: risks and prevention.

PMID- 12503361
TI  - Combined spinal epidural analgesia is the preferred technique for labour
      analgesia.
AB  - To justify its place as the preferred method of pain relief in labour, CSE must
      demonstrated a clear superiority over epidural analgesia. Looking at the relative
      efficacy of the two techniques failure rates appear to be equal. Speed of onset
      may be faster with an initial spinal injection although perhaps only clinically
      relevant in advanced labour where the quality of analgesia may sometimes be
      better. CSE would not seem to offer significant advantage in terms of mode of
      delivery or the ability to ambulate. The side effects of the technique are
      somewhat more concerning as CSE would appear to carry slightly greater risk than
      epidural analgesia, most notably in neurological sequelae and the effects of
      intrathecal opioids. Certainly CSE confers no benefit in terms of cost. What then
      is the place of CSE in labour analgesia? Its potential benefit makes it a
      reasonable option when there is a clear clinical advantage such as requests for
      analgesia in late labour or where maternal distress is extreme or where epidural
      analgesia has been ineffective. However even in such situations the slight
      increase in risk must be weighed against the possible advantage. Consequently the
      CSE cannot at the present time be recommended as the preferred option for labour
      analgesia.

PMID- 12503362
TI  - HIV and reproduction: ethical considerations.

PMID- 12503363
TI  - Anaesthesia for in vitro fertilization.

PMID- 12503364
TI  - A recent update on breast reconstruction.

PMID- 12503365
TI  - [Basal ganglia participation in the organization of behavior].

PMID- 12503366
TI  - [Populations of behavior-reactive neurons in the monkey neostriatum].
AB  - Comparative analysis of the unit activity of the monkey putamen during multistage
      behavior showed that neurons of the putamen are active during all the behavioral
      actions. It was established that the number of the behavior-related neurons
      changes considerably less than number of neurons which reorganize their activity
      at the time. Reorganization of unit activity in the putamen is considered as
      reflecting the efferent code which controls behavior, and the degree of
      reorganization--as a measure of change of this code in relation to organization
      of ongoing behavioral action. It has been discovered that the change in the
      number of the active neurons at various steps of behavior and reorganization of
      their activity occurs independently. It may be related to two main afferent
      systems of striatum: ascending from rhe brain stem, and corticofugal which brings
      differentiated information to the neuronal net of striatum from various parts of
      the cortex.

PMID- 12503367
TI  - [Differentiating activity of monkey putamen neurons during performance of the
      alternative spatial choice].
AB  - Single unit activity was recorded in monkeys in three putamen zones learned a
      bimanual operant activity during performance of the task of alternative spatial
      choice. The neuronal reactions were specially analyzed by the criteria as
      follows: a) differentiation of the side of reward (differentiating--non
      differentiating reactions); b) character of reaction by duration (tonic-phasic);
      c) laterality (contra- and ipsilateral reactions as related to hemisphere); d)
      frequency of background activity. It was shown that differentiating cell
      activity, especially their tonic part and in still greater degree contra-lateral
      tonic reactions most closely correlate with behavioral aspects of the program.
      The assumption that differentiating activity, unlike non-differentiating one, is
      the reflection of not only morphological and neurochemical characteristic
      features of nervous elements of putamen but of its functional uniformity in
      relation to external determinants of behavior, was put forward.

PMID- 12503368
TI  - [Sequential rearrangements of ensemble activity of the putamen neurons of monkeys
      as a correlate to continuous behavior].
AB  - Simultaneous recording of unit activity of 6-8 putamen neurons in two monkeys (M.
      nemestrina and M. mulatta) during performance of the task of alternative spatial
      choice, was carried out. The extent of rearrangements of the activity in the
      groups of neurons with the transition from every step of the behavioral program
      to the next one and the degree of difference in mosaics of reactivity, forming at
      every step with a different variants of performance, were evaluated using
      discriminative analysis. The rearrangements of the impulse activity were recorded
      in all steps of the program. The dynamics of rearrangements with the choice of
      right or left feeder was different, which resulted in appearance of significant
      differences in mosaics of reactivity at the stage of decision making and
      receiving reward. The rearrangements preceding the task-oriented movement of one
      hand were more pronounced in the contralateral hemisphere. The volume of
      rearrangements may increase with the performance of movement but the differences
      of mosaics formed during the movement of right and left hand are decreasing. At
      the stage of reception of the reward, the rearrangements were greater in case the
      animal chose the certain (left) feeder irrespective of the side of recording the
      unit activity.

PMID- 12503369
TI  - [Reflection of space characteristics of an acoustic signal in the neuronal
      activity of the caudate nucleus].
AB  - In chronic experiment, responses of single neurons of the caudate nucleus (CN) to
      spatial characteristics of acoustic signal have been investigated in dogs. It is
      shown that 92% of neurons of the caudate nucleus' head responding to sound
      stimulation asymmetrically react to contra- and ipsilateral monoaural, with a
      greater efficacy of a contralateral stimulation. For 50% of the CN neurons
      simultaneous sound inputs appear more effective in comparison with contralateral
      stimulation. 77% of the caudate neurons responding to sound have shown
      sensitivity to change of the value and sign of the interaural delay.

PMID- 12503370
TI  - [Analysis of the morphological substrate of information processing in the
      striatum based on organizational characteristics of its afferent projections].
AB  - By the method of axonal transport of the retrograde markers, the afferent
      projections, coming from functionally different cortical and subcortical
      structures to various segments of the caudate nucleus, were investigated in the
      putamen and the nucleus accumbens of the dog brain. On the basis of the
      determined peculiarities of the spatail organization of these projections, the
      morphological aspects of the segregated and convergent conducting and processing
      of the information in the striatum, which underlie their functioning, were
      analyzed.

PMID- 12503371
TI  - [Analysis of the morphological substrate of information processing in the dog
      brain pallidal complex based on organizational characteristics of its afferent
      projections].
AB  - Projections from functionally diverse cortical and subcortical structures
      (cortex, amygdaloid body, substantia nigra, ventral tegmental area, and thalamus)
      to the pallidum (globus pallidus, entopeduncular nucleus and ventral pallidum)
      were studied in dogs using the method of axonal transport of the retrograde
      markers. Anatomical aspects of both the functional heterogeneity of the pallidal
      structures and integrative processing of information which underlie the
      mechanisms of adaptive behavior, were analyzed on the basis of the results
      obtained.

PMID- 12503372
TI  - [Neurons of the human basal ganglia (striatum and basolateral amygdala)
      expressing the enzyme NADPH-d].
AB  - In human striatum and basolateral amygdala NADPH-d+ neurons were revealed (after
      Vincent et al., 1983); and in striatum strio-cortical neurons were also revealed
      using DiI marker (after Dahtstrom and Belichenko, 1995). The NADPH-d+ neurons
      were numerous in both formations. Staining of NADPH-d+ neurons with their
      processes, and our previous study of striatal and amygdalar human neurons by
      Golgi method made it possible to identify the species of neurons with their
      assessment as sparsely or densely branched. The main efferent neurons of striatum
      and basolateral amygdala (densely branched medium spiny and bushy spiny,
      respectively) and their densely branched interneurons were not marked. Efferent
      NADPH-d+ neurons included the most numerous ones in both formations. A projection
      of reticular striatal neurons to cortex was also shown. The NADPH-d+ interneurons
      belonged to sparsely branched forms. In striatum they included slender-dendritic
      and long-dendritic bipolars (numerous), ordinary bipolars, twisted and large poor
      dendritic cells; in amygdala--the same bipolars and radial cells. Thus, the NADPH
      d positive cells in the formations under study were represented by more "ancient"
      or less structurally complex cell forms.

PMID- 12503373
TI  - [The role of substantia nigra in the cognitive activity in cats].
AB  - The role of substantia nigra (SN) in the cat cognitive activity of different
      complexity degree, was investigated by original technique. Neurosurgery or
      neurochemical SN switching off leads to reliable disturbances of condition,
      reflexes, generalization and abstraction. Rehabilitation was possible after
      pharmacological stimulation of dopaminergic, partly GABA-ergic, and cholinergic
      systems. Stimulation of serotonin system was ineffective.

PMID- 12503374
TI  - [Locomotor behavior in rats after separate and simultaneous intrastriatal
      microinjections of GABA-ergic drugs].
AB  - The effects of daily intrastriatal bilateral microinjections of 45 mog GABA, 1
      mcg of picrotoxine and 5 mcg of bicuculline on rats, were investigated.
      Impairment of the avoidance conditioning in shuttle box was registered in rats
      with picrotoxine or bicuculline and the choreo-myoklonic limb jerks, with
      distinct generalization stage after the picrotoxine microinjections. The combined
      microinjections--GABA with picrotoxine, and bicuculline with picrotoxine
      inhibited the hyperkinesis manifestation and changed avoidance conditioning
      behaviour and open-field locomotor activity. The findings suggest involvement of
      neostriatal GABAergic system in avoidance conditioning and complex locomotor
      behavioural acts regulation. The ultimate aim of the research is to find the
      cause, neurotransmitter mechanisms of neuromotor diseases, and to research
      principal new orders in treatment of neuromotor deviations.

PMID- 12503375
TI  - [Specifics of the neurotensin effect on rat motor responses to positive and
      negative conditioned stimuli].
AB  - Comparative analysis of effects of neurotensin microinjections into caudate
      nucleus and substantia nigra on thirst-motivated motor conditioned reactions in
      rats, was performed. The microinjections facilitated extinction of conditioned
      reactions in response to negative stimuli and did not affect realization of
      responses to positive conditioned signals. Behavioral effects of neurotensine in
      rats are connected with the normalising of motivational and emotional states of
      animals and may be explained by restoration of monoaminergic systems interaction.

PMID- 12503376
TI  - [Genetic determination of the neurophysiological mechanisms of the cortico
      subcortical integration of bioelectrical activity of the brain].
AB  - Contribution of genetical factors to neurophysiological mechanisms of cortico
      subcortical integration was investigated in 12 pairs of the monozygotic and 5
      pairs of dizygotic twins (aged from 18 to 25). In each pair of twins as well as
      in all 544 unrelated pairs of subjects from both groups, interpairs similarity of
      the character of the spatial interaction of bioelectrical activity of the
      neocortex for different combinations of statistical correlations of EEG (from 16
      monopolar electrodes) was estimated. The data obtained allow to suggest a higher
      common population invariance and a relatively small hereditary and phenotypic
      variability of morphofunctional systems, which underlie neurophysiological
      mechanisms of the brain integration in general. Apparently, the formation of the
      brain stem and subcortical regulatory structures in the ontogenesis, the
      structures that play the main role in the realization of system combination of
      different parts of the brain into united formation, occurs to all individuals
      according to a single principle since its disturbance can probably affect the
      fundamental monomorphal features of the species. In turn, one can expect a great
      interindividual variability of establishing of the intraregional connections of
      neocortex, the role of genetic and environmental factors in the formation of
      short and relatively long interactions being complex.

PMID- 12503377
TI  - [Possible mechanisms of amygdala participation in the regulation of gastric motor
      activity].
AB  - Mechanisms of the amygdala central nucleus (CNA) influence on gastric motor
      reflex activity were studied in electrophysiological and neuroanatomical
      experiments in Wistar rats. In the anaesthetized animals, electrical stimulation
      of the CNA affected spontaneous gastric motility and caused inhibitory as well as
      excitatory changes of vagus-induced gastric relaxation. The most significant and
      mainly inhibitory effects were observed under the stimulation of the medial CNA.
      Microinjection of the anterograde tracer Phaseolus vulgaris-leucoagglutimn (PHA
      L) into the different divisions of the CNA revealed direct projections from its
      dorso-medial portion to the gastric related area of the dorsal vagal complex.
      Electrical stimulation of this amygdaloid area was found to change activity of
      the bulbar gastric related neurons. Inhibitory and excitatory changes of their
      vagus-induced responses under the amigdala stimulation were manifested as a
      general modulation of all phases of the reaction or a selective modulation of
      some of them. These mechanisms may underlie the amygdalo-fugal modulation of
      gastric motor reflex activity.

PMID- 12503378
TI  - [Tremor characteristics in the norm and in the diagnosis and treatment of
      parkinsonism].
AB  - With the aid of tensotremorography, a voluntary effort was recorded and
      characteristics of involuntary and voluntary components of the hands'
      isometrically recorded efforts were studied. The revealed frequency ranges of the
      oscillations spectral density's changes corroborate existence of two
      suprasegmental systems of movements control, the systems being related to
      voluntary control and a current control of the efforts maintaining or preserving
      a posture. Results of cross-correlation analysis of the hands' efforts maintained
      under conditions of a visual feedback are demonstrated in norm and in central
      disorders of the movement control system.

PMID- 12503379
TI  - The family: an important nursing resource for holistic client care.

PMID- 12503380
TI  - Smoking higher among female nurses.

PMID- 12503381
TI  - Time to change the image of nursing.

PMID- 12503382
TI  - Advanced cardiac life support becomes basic.

PMID- 12503383
TI  - Reducing anxiety in patients and families discharged from ICU.

PMID- 12503384
TI  - Chickenpox: a vaccine preventable disease.

PMID- 12503385
TI  - Six steps to ethical leadership in health care.

PMID- 12503386
TI  - Managing disaster: turning chaos into opportunity for improvement.

PMID- 12503387
TI  - Our readers speak out about ethics and health care.

PMID- 12503388
TI  - Biotransformation of trichloroethene by pure bacterial cultures.
AB  - From natural samples 11 isolates able to remove trichloroethene (CCl2CHCl) from
      an aqueous environment were obtained which were capable of cometabolic
      degradation of CCl2CHCl by an enzyme system for phenol degradation. At an initial
      CCl2CHCl concentration of 1 mg/L, the resting cells of particular cultures
      degraded 33-94% CCl2CHCl during 1 d and their transformation capacity ranged from
      0.3 to 3.1 mg CCl2CHCl per g organic fraction. An analysis of a mixed phenol-fed
      culture with an excellent trichloroethene-degrading ability found a markedly
      minority isolate represented in the consortium to be responsible for this
      property. This culture degraded CCl2CHCl even at a low inoculum concentration and
      attained a transformation capacity of 14.7 mg CCl2CHCl per g. The increase in
      chloride concentration after degradation was quantitative when compared with the
      decrease in organically bound chlorine. The degree of CCl2CHCl degradation was
      affected by Me2S2; this substance can significantly reduce the degrading ability
      of some tested cultures (> 60%); however, it does not cause this inhibition with
      others.

PMID- 12503389
TI  - Production and properties of asparaginase from a new Erwinia sp.
AB  - Asparaginase production by a mesophilic strain of Erwinia sp. was examined; the
      maximum of activity was found at 40 degrees C and pH 8.5. Among the various
      carbon sources, mannitol was shown to be the best for production of activity.
      Inorganic nitrogen sources were better than the organic ones. The enzyme activity
      was not inhibited by 10 mmol/L metal ions (Na+, K+, Mg2+, Ca2+, Ba2+, Co2+, Ni2+,
      Zn2+); the activity was strongly inhibited by addition of EDTA. L-Arginine, DL
      alanine, L-asparagine and L-glutamine stimulated the L-asparaginase production by
      3.9, 1.7, 4.3 and 4.0 fold, respectively. The combination of L-arginine, L
      asparagine and L-glutamine synergistically stimulated the asparaginase up to 5.8
      fold.

PMID- 12503390
TI  - Specific growth rate of bifidobacteria cultured on different sugars.
AB  - The ability of six bifidobacterial strains (3 of human origin and 3 isolates from
      fermented milk products) to utilize glucose, lactose, melezitose, sucrose,
      raffinose, and stachyose was determined. Dairy-related bifidobacterial strains
      were identified as Bifidobacterium animalis (2 strains) or as B. pseudolongum (1
      strain). Human strains included B. longum (2 strains) and B. breve (1 strain).
      All strains fermented lactose, sucrose, raffinose, and stachyose. Melezitose was
      utilized only by B. longum. B. pseudolongum did not ferment either glucose or
      melezitose. All isolates had a higher specific growth rate on raffinose and
      stachyose than on glucose. Dairy strain grew slowly on glucose compared to human
      strains.

PMID- 12503391
TI  - Antimicrobial activity of FeIII, CuII, AgI, ZnII and HgII complexes of 2-(2
      hydroxy-5-bromo/nitro-phenyl)-1H- and 2-(2-hydroxyphenyl)-5-methyl/chloro/nitro
      1H-benzimidazoles.
AB  - Antimicrobial activity of 2-(2-hydroxyphenyl)-5-R5-1H-benzimidazoles, 2-(2
      hydroxy-5-R5'-phenyl)-1H-benzimidazoles and their FeIII, CuII, AgI, ZnII and HgII
      nitrate complexes was tested toward Staphylococcus aureus, Staphylococcus
      epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,
      Salmonella typhi, Shigella flexneri, and Proteus mirabilis. Antifungal activity
      was tested against Candida albicans. Benzimidazole benzene ring substituents
      increase the antimicrobial activity, phenol ring substituents decrease it. The
      ligands show an antibacterial effect against only S. aureus whereas AgI and HgII
      complexes of the ligands have a higher activity with respect to the other
      complexes to all the bacteria. On the other hand, FeIII complexes show a
      considerable activity against S. aureus and S. epidermidis.

PMID- 12503392
TI  - In vitro antifungal activity of 3-phenyl-2H-benzoxazine-2,4(3H)-diones.
AB  - A series of 81 3-phenyl-2H-benzoxazine-2,4(3H)-diones with substitution at C(6)
      on the benzoxazine ring and on the phenyl moiety was synthesized; the compounds
      were evaluated for antifungal activity against five strains of potentially
      pathogenic fungi (Absidia corymbifera, Aspergillus fumigatus, Candida albicans,
      Microsporum gypseum and Trichophyton mentagrophytes). Structure-activity
      relationships against T. mentagrophytes and M. gypseum were determined using the
      Free-Wilson method, which was further combined with the approach of Hansch. In
      vitro antifungal activity becomes higher with increasing electron-accepting
      ability of the substituents on the phenyl ring, and with increasing
      lipophilicity.

PMID- 12503393
TI  - Isolation and identification of Streptomyces sp. and assay of its exocellular
      water-soluble blue pigments.
AB  - A bacterial strain producing a great amount of blue pigment during submerse
      fermentation was isolated and identified. Based on morphological characteristics,
      cell-wall chemotype and sequence of 16S rRNA gene, the strain should belong to
      the genus Streptomyces; it had 99.4% homology of 16S rRNA gene sequence with that
      of Streptomyces indigocolor. The pigment production by the strain was affected by
      carbon and nitrogen sources. The main components of the pigment mixture (detected
      by HPLC and TLC) were tentatively classified as actinorhodin-related compounds.
      The pigment was relatively stable against light and higher temperature but was
      sensitive to low pH. The preliminary acute-toxicity determination showed that the
      pigment was nontoxic (LD50 > 15 mg/g).

PMID- 12503394
TI  - Response regulator ChiR regulates expression of chitinase gene, chiC, in
      Streptomyces coelicolor.
AB  - Transcription from the chiC promoter, directing expression of the chitinase gene,
      chiC, in Streptomyces coelicolor, was analyzed using xylE reporter gene and high
      resolution S1-nuclease mapping. The transcription from the chiC promoter was
      induced by chitin, and this induction was dramatically reduced in the S.
      coelicolor chiR-disrupted strain. This indicated a dependence of chiC expression
      upon the chiR gene encoding a response regulator protein. To investigate this
      relationship, the S. coelicolor ChiR was overproduced using Escherichia coli T7
      RNA polymerase expression system. However, gel mobility shift-assay with such a
      purified ChiR showed no binding in the chiC promoter region, which indicates a
      lack of specific phosphorylation of E. coli overproduced ChiR that is necessary
      for DNA-binding activity of response regulators.

PMID- 12503395
TI  - Effect of Brestan on Saccharomyces cerevisiae during continuous cultivation.
AB  - An increase in Brestan concentration in nutrient media decreased the content of
      protein, phosphorus, total ribonucleic acid, activity of pyruvate carboxylase and
      isocitrate lyase in cells of Saccharomyces cerevisiae parent strain and
      respiratory deficient (RD) mutant while the trehalose content increased. The
      respiration quotient value for the RD mutant was higher than for the parent
      strain. The RD mutant lacked cytochrome aa3; cytochrome c and b contents were
      lower than those of the parent strain.

PMID- 12503396
TI  - Influence of cultivation conditions on citrate production by Aspergillus niger in
      a semi-pilot-scale plant.
AB  - The influence of some fermentation parameters on the semi-pilot scale (alteration
      of growth conditions, e.g., sugar concentration, incubation temperature and
      initial pH) on citrate production was demonstrated in parent and mutant strains
      of Aspergillus niger. Raw material from sugar industry (cane molasses) was
      examined as basal fermentation medium in a stirred stainless-steel 15-L
      fermentor. After growth on medium with 150 g/L sugar, the parent strain produced
      51.2 g/L citric acid; the mutant strain achieved production maximum of 96.2 g/L.
      Comparing the growth, kinetic (volumetric substrate uptake rate, rate of
      substrate consumption and volumetric productivity rate) and production parameters
      it was found that the mutant strain grows more rapidly, with slightly changed
      morphology (intermediate, shiny round pellets with diameter 0.6-0.7 mm), and
      exhibits a higher citrate production and higher efficiency of sugar utilization.

PMID- 12503397
TI  - Recombinagenic effect of cryptolepine in uvsH+//uvsH+ and uvsH//uvsH diploid
      strains of Aspergillus nidulans.
AB  - Recombinagenic potential of the alkaloid cryptolepine was evaluated in two
      diploid strains of Aspergillus nidulans--a wild type strain (uvsH+//uvsH+) and a
      DNA-repair-deficient one (uvsH//uvsH). Treatment of both strains with
      cryptolepine failed to alter colony growth in culture; its recombinagenic
      potential was determined by the homozygotization index (in which events of
      mitotic exchange may cause expression of genes previously masked by the dominant
      allele). Mitotic crossing-overs were induced by 7 and 14 mg/L doses of
      cryptolepine in both diploid A. nidulans strains.

PMID- 12503398
TI  - The effect of fulvic acids on the toxicity of lead and manganese to arbuscular
      mycorrhizal fungus Glomus intraradices.
AB  - The effect of fulvic acids (FA) on arbuscular mycorrhizal (AM) fungi and on the
      toxicity of lead and manganese toward these symbionts were demonstrated in vitro.
      Incubation of root segments colonized with the AM fungus Glomus intraradices in
      undiluted fraction of FA (813 mg/L carbon) decreased an outgrowth of intraradical
      hyphae. Diluted FA solutions (< 271 mg/L C) did not influence the proportion of
      root segments bearing proliferating hyphae; solution containing 27.1 mg/L C even
      increased the proliferation. A decrease of heavy metal toxicity toward the fungus
      was observed when FA (81.3 mg/L C) were added to the solutions containing higher
      concentrations (< or = 100 mumol/L) of Mn and Pb; the positive effect of FA was
      not significant at higher concentrations of metals (0.5 mmol/L). A short-term
      cultivation of six different saprophytic microorganisms--three actinomycetes and
      three filamentous fungi--on the FA media (81.3 mg/L C) did not result in a
      modification of hyphal proliferation from the root segments subsequently
      incubated in these media.

PMID- 12503399
TI  - Vegetative survival, akinete and zoosporangium formation and germination in some
      selected algae as affected by nutrients, pH, metals, and pesticides.
AB  - Lack of nitrogen, phosphorus, or all nutrients, extremes of pH (< 4, > 11),
      presence of 'heavy' metals (Co, Cu, Zn, Hg, Pb; 0.5-10 ppm) or pesticides
      (carbofuran, 2,4-D, dithane, phorate, or bavistin; 1-50 ppm) decreased to various
      extent or completely inhibited the survival or vegetative cells in all studied
      algae. The formation of akinetes, their viability and germination in Anabaena
      iyengarii, Westiellopsis prolifica, Nostochopsis lobatus and Pithophora oedogonia
      and the formation of zoosporangia, their viability, and the germination of
      zoospores in Cladophora glomerata and Rhizoclonium hieroglyphicum was affected.
      The formation of viable akinetes or zoosporangia was shown to be directly linked
      with vegetative cell survival and growth; it could not be induced by any chemical
      stress imposed.

PMID- 12503400
TI  - Plectin-like proteins are present in cells of Chlamydomonas eugametos
      (Volvocales).
AB  - Using both monoclonal and polyclonal antibodies against mammalian plectin
      (multifunctional protein cross-linking cytoskeletal structures, mainly
      intermediate filaments, in mammalian cells), several putative isoforms of plectin
      like proteins were found in protein extracts from the green alga Chlamydomonas
      eugametos (Volvocales). Immunofluorescence and immunoblotting revealed that some
      of the plectin-like proteins were present in perinuclear region or localized near
      the cell wall, probably being attached to the cytoplasmic membrane.

PMID- 12503401
TI  - Preincubation of Mesorhizobium ciceri with flavonoids improves its nodule
      occupancy.
AB  - Strains of M. ciceri, symbionts of chickpea (Cicer arietinum) were incubated with
      the flavonoids naringenin, daidzein and quercetin which have earlier been
      reported as inducers and inhibitors of nodABC-lacZ fusion of M. ciceri.
      Preincubation of M. ciceri with naringenin and daidzein (100 nmol/L) for 1 d
      improved the competitive ability of the inoculated strain while preincubation
      with quercetin decreased the nodule occupancy of inoculated strain under sterile
      conditions. Under non-sterile conditions induced strains of Rcd 301 and HT-6
      formed by 23 and 18% more nodules, respectively, than untreated control.
      Quercetin-treated strains showed by 13-20% fewer nodules than untreated controls.
      Therefore, it is possible to regulate the competitive ability of inoculated
      strains by flavonoid treatment.

PMID- 12503402
TI  - Effects of storage time and temperature on the infectivity and effectiveness of
      Frankia entrapped in polyacrylamide gel.
AB  - Four Frankia-Casuarina endosymbiont strains were tested for their infectivity and
      effectiveness on C. equisetifolia plants after 1 d, 3 and 6 months of Frankia
      storage at 7, 28 and 40 degrees C as liquid-cultures and polyacrylamide gel (PAG)
      immobilized inocula. At lower temperature the number of nodules was the same or
      higher than control for liquid inocula except after 6 months of storage. For the
      PAG-entrapped Frankia lower numbers of nodules were recorded due to the use of
      high Frankia titers. In general, the results showed comparable plant dry mass,
      total nitrogen, root to shoot and nodules to plant ratios at lower temperature
      treatments. Increasing time and temperature was accompanied with reduced
      infectivity and effectiveness on inoculated plants. No nodulation was scored on
      plants inoculated with liquid and PAG-entrapped inocula stored at 40 degrees C
      for 6 months; subsequently, plant growth was inhibited. The variations in results
      obtained for different strains and treatments lead to variations in plant
      nitrogen-fixing ability. The use of PAG as a carrier for different Frankia
      strains is suggested; the recommended storage temperature for PAG-immobilized
      Frankia in 7-28 degrees C for up to 3 months.

PMID- 12503403
TI  - Immunology of the pathogen virulence and phytotoxin production in relation to
      disease severity: a case study in sheath blight of rice.
AB  - Polyclonal antibodies against purified Rhizoctonia solani toxin obtained from
      infected rice sheath tissues (sheath blight toxin, SBT) and culture filtrates
      (culture filtrate toxin, CFT) were developed in rabbit and chicken. The IgG was
      isolated from serum and egg yolk of rabbit and chicken, respectively, and their
      specificity was investigated by indirect ELISA. Antibodies developed against CFT
      and SBT in rabbits exhibited relatively higher titer values when compared to
      chicken antibodies. Positive correlation was observed between the degree of
      sheath blighting and the levels of antigens induced by each isolate during sheath
      blight symptom development as detected by rabbit SBT antibody and the isolate RS7
      was identified as most virulent. Optimization of incubation period for maximum
      toxin production in liquid medium and rice sheaths indicated that the production
      of CFT and SBT is maximum after 15 d and 6 d of pathogen inoculation. Studies of
      the possible translocation of RS-toxin in rice plants upon inoculation with R.
      solani showed downward translocation as detected by rabbit/chicken SBT
      antibodies. Since plant inoculation required a higher concentration of inoculum
      and maintenance of plants, serological assay by ELISA is more sensitive than
      whole-plant assays in detecting RS-toxin, with the advantage that ELISA also
      allows rapid determination of RS-toxin production.

PMID- 12503404
TI  - Identification and characterization of Clostridium paraputrificum, a chitinolytic
      bacterium of human digestive tract.
AB  - A strictly anaerobic, mesophilic and chitinolytic bacterial strain was isolated
      from human feces. Based on morphological and physiological properties and 16S
      rRNA sequence analysis the strain was identified as Clostridium paraputrificum.
      The strain utilized chitin and N-acetyl-D-glucosamine, grew on glucose and
      hydrolyzed starch. Cultivation of the strain with colloidal chitin as the growth
      substrate resulted in the production of gas (hydrogen and carbon dioxide) and
      formation of acetate and lactate (21.6 and 18.9 mmol/L, respectively) and only
      small quantities of propionate and butyrate (1.7 and 2.6 mmol/L, respectively).
      In the course of a 10-d cultivation with chitin, the endochitinase activity was
      detected after 1 d and gradually increased, reaching maximum after 3 d (251
      nkat/L N-acetyl-D-glucosamine). The beta-N-acetylglucosaminidase activity
      appeared just at the beginning of the cultivation, increased to day 2 and then
      remained nearly constant. More than 90% of chitin added was degraded within 2 d
      of cultivation. On the zymogram of the extracellular chitinolytic complex were
      visible at least 6 isoenzymes with molar mass 43.5-65.0 kDa. The temperature
      optimum of endochitinase and beta-N-acetylglucosaminidase activities was 50
      degrees C; the optimum activity of both enzymes was found at pH 4-6.

PMID- 12503405
TI  - Evaluation of selected features of Staphylococcus cohnii enabling colonization of
      humans.
AB  - Based on iron utilization, sensitivity to skin fatty acids, lipolytic and
      proteolytic activity the potential abilities of Staphylococcus cohnii strains to
      colonize humans were evaluated. The investigation included 60 strains that belong
      to both subspecies, viz. S. cohnii ssp. cohnii and S. cohnii ssp. urealyticus.
      Strains were isolated from different sources of the Intensive Care Unit and from
      non-hospital environment. Most of the strains were multiple antibiotic-resistant.
      Strains of both subspecies revealed a relatively low iron requirement. These
      strains were capable of utilizing iron bound in oxo acids and from host iron
      binding proteins. S. cohnii ssp. urealyticus were more effective in iron uptake
      than S. cohnii ssp. cohnii. All investigated strains revealed sensitivity to skin
      fatty acids, but S. cohnii ssp. urealyticus strains were more resistant. Special
      features of strains of this subspecies promote colonization of humans.

PMID- 12503406
TI  - Treatment of experimental adjuvant arthritis with the combination of methotrexate
      and lyophilized Enterococcus faecium enriched with organic selenium.
AB  - The efficacy of combination therapy with methotrexate (MTX) and probiotic
      bacteria Enterococcus faecium enriched with organic selenium (EFSe) in rats with
      adjuvant arthritis was determined. Rats with adjuvant arthritis were given MTX
      (0.3 mg/kg 2-times weekly, orally); lyophilized E. faecium enriched with Se (15
      mg/kg, 5 d per week, orally); and a combination of MTX plus EFSe for a period of
      50 d from the immunization. Levels of serum albumin, serum nitrite/nitrate
      concentrations, changes in hind paw swelling, arthrogram score, bone erosions,
      whole body bone mineral density (BMD) and bone mineral content (BMC) were assayed
      in the rats as variables of inflammation and destructive arthritis-associated
      changes. Treatment with MTX and with the combination MTX + EFSe significantly
      inhibited markers of both inflammation and arthritis. Significant differences in
      favor of combination therapy with MTX + EFSe as compared to MTX alone were seen
      in serum albumin concentration, hind paw swelling and arthrogram score.
      Reductions in radiographic scores were also more pronounced in the combination
      therapy group. Combination therapy, but not MTX alone, inhibited the reduction of
      BMD and BMC; treatment with lyophilized EFSe alone had no significant effect on
      adjuvant arthritis in rats. The potent therapeutic effect of low dosage MTX
      therapy in combination with lyophilized EFSe on adjuvant arthritis in rats was
      shown.

PMID- 12503407
TI  - Characteristics of clinical Acinetobacter spp. strains.
AB  - Resistance to 13 antimicrobial agents, resistance to the bactericidal activity of
      human serum, hydrophobic properties, lipolytic activity and production of
      histamine were determined in a total of 50 clinical Acinetobacter spp. strains
      (A. baumannii, A. lwoffii, A. calcoaceticus, A. haemolyticus). None of the tested
      isolates showed resistance to meropenem and none of A. lwoffii, A. calcoaceticus
      and A. haemolyticus strains were resistant to amikacin. Forty-six strains (92%)
      manifested resistance to ampicillin, 90% to cefuroxime, 68% to ciprofloxacin, 58%
      to piperacillin, gentamicin and cotrimaxazole, 50% to cefotaxime, 44% to
      amikacin, 42% to ceftazidime, 38% to piperacillin/tazobactam, 24% to netilmicin
      and 16% to ampicillin/sulbactam. In particular, A. baumannii and A. calcoaceticus
      strains showed considerable antibiotic resistance. Thirty-one isolates (62%)
      showed serum resistance; intermediate sensitivity was found in 19 isolates (38%).
      The majority of the strains (72%) demonstrated a strongly hydrophobic character;
      16% of isolates exhibited moderate hydrophobic properties. All strains showed
      lipolytic activity; production of histamine was detected in 14 of 43 strains
      examined.

PMID- 12503408
TI  - Sharing trans-tasman nursing experiences.

PMID- 12503409
TI  - Learning to look through the same window.

PMID- 12503410
TI  - A service with a social conscience.

PMID- 12503412
TI  - Linking housing and health status.

PMID- 12503411
TI  - Why are some people healthy and others not?

PMID- 12503413
TI  - MECAs--where to from here?

PMID- 12503414
TI  - The natural holistic imperative.
AB  - Biodiversity is nature's expression of the principle of holism. This 'natural
      holistic imperative' is manifested in all aspects of the environment. While
      environmental health originated through a concern for protecting humans from
      environmental risks, it is now concerned with protecting the environment from the
      activities of humans. In order to protect the health of humans, there is a need
      to be concerned with protection of the biosphere. Moreover, the environmental
      crisis is essentially a crisis in spirituality, and a spirituality that respects
      and nurtures the non-human parts of our universe as much as it does the human
      ones is likely to be the only means of securing the health and happiness of
      humanity.

PMID- 12503415
TI  - Caregivers talk about experiences of caring for an older person with dementia.
AB  - This study explored caregivers' experiences of caring for an older person with
      dementia by listening to the voices of 15 carers to identify successful
      management strategies. Some successful management strategies did emerge none saw
      their approach as a 'successful strategy', just that things worked on certain
      days. It is suggested that families can be prepared for a 'career' in caring and
      that early assessment and diagnosis is essential.

PMID- 12503416
TI  - Intuition and visual art: student nurses' projection into experiences of elderly
      women.
AB  - The aim of the present study was to determine the degree to which student nurses
      in Sweden were able to predict responses of elderly women to 12 paintings. The
      result showed that the students were able to enter into situations and
      experiences of the elderly women. They used intuitive knowing-they were
      emotionally involved and used cognitive knowing during the prediction process. It
      could be concluded that nurse educators concerned with finding new directions to
      develop intuition skills might consider visual art of considerable value.

PMID- 12503417
TI  - Philophonetics counselling for prevention of burnout in nurses.
AB  - Nurses who have self-reported burnout rate their experiences prior to and after
      the intervention to reveal significant reductions in their burnout experience on
      all items. Philophonetics counselling interventions address feelings of
      victimization, disorientation, loss of decision making power, lack of
      interpersonal boundaries and disconnection from one's inner being and one's
      internal resources.

PMID- 12503418
TI  - An examination of factors influencing natural therapy use in the Royal District
      Nursing Service.
AB  - Fifty-six nurses employed by the Royal District Nursing Service (RDNS) of South
      Australia completed a questionnaire examining factors that influence and
      constrain natural therapy use in nursing practice. Other issues examined included
      natural therapy education; natural therapy knowledge base; therapies utilised in
      practice; and types of patients and health conditions exposed to these therapies.

PMID- 12503419
TI  - [Changes of evoked potentials caused by sound signals with different localization
      characteristics].
AB  - Characteristics of the mismatch negativity (MMN) were studied by presenting the
      subjects with four blocks of stimuli containing standard series of clicks (90%)
      simulating a stationery sound image located in the head midline, and one of three
      different deviant series of clicks (10%) simulating either a stationary sound
      image located near the left ear or a moving sound image which shifted from the
      head midline to the left ear or in the opposite direction. All the deviant
      stimuli elicited the MMN with the minimal peak amplitude and the greatest latency
      evoked by the deviant series of clicks simulating the sound image moving from the
      head midline to the left ear. These findings suggest that the MMN may be
      considered as a pre-perceptual physiological measure of the discrimination
      accuracy for the sound signals with various spatial locations.

PMID- 12503420
TI  - [The resolution and discrimination of images in the visual system].
AB  - We analysed the conformity of optic and retinal cones anatomy factors by the two
      point test. Obtained by F. Campbell and R. W. Gubish, the point spread function
      has a width of about 1 arc min. Cones sizes are equal to 0.5 arc min in the
      fovea. Functional pixel consists of 3-5 cones under the point spread function.
      Such an organisation in very useful in decreasing the samping noise of receptors.
      We carried out psychophysical investigations to show a consensus among the optic,
      receptors', and neuronal levels. In experiments we studied changes of the two
      point pattern perception in respect to the points separation, measured the
      orientation threshold of small size stimuli. Data were compared with optical
      point-spread function, the hexagonal mosaic of cones, and line spread function of
      spatial elements, which form spatial frequency channels at the cortical level.

PMID- 12503421
TI  - [Sensitivity of the neurons in the auditory inferior colliculus of mice to the
      direction of the shift of broadband spectral notch noise].
AB  - Series of a notch noise with regular shifts of the notch center frequency: one-
      from low frequencies to high frequencies and the other--from high frequencies to
      the low, were synthesized. The notch noise series imitated sound source vertical
      moving. Single neuron's responses of inferior colliculus of the house mouse (Mus
      musculus) to the notch-noises altered with notch central frequency varying
      through excitatory and inhibitory frequency response areas in neurones' receptive
      fields. The neural responses alteration to the notch noise varying depended on
      the bandwidth of notch. Disinhibition in inhibitory side band could be higher if
      the notch overlying the inhibitory areas followed the notch overlying the
      excitatory areas. The data obtained make it possible to consider the excitatory
      and inhibitory interaction as a mechanism of neural sensitivity to the notch
      moving direction. Neurones' response set could provide information about sound
      source moving over auditory space.

PMID- 12503422
TI  - [Instrumental behavior in the activation or blockade of the neostriatum
      muscarinic receptors].
AB  - In four dogs, microinjections of carbacholine enhanced the tonic component and
      inhibited the physical component of the instrumental defence reflex, put in order
      the posture, and increased its components' amplitude. Microinjections of
      raclopride yielded a similar though a less obvious result. Differentiation
      stimuli provided the greatest effect of both substances. A sharp improvement
      occurred in differentiation of sound signals. Microinjections of pyrenzepine
      yielded an opposite result. The data obtained are explained proceeding from the
      idea of a presence of the neostriatum's two efferent outputs exerting opposite
      effects on their targets, and the role of muscarine and dopamine receptors in
      their triggering and blockade.

PMID- 12503423
TI  - [Comparison of the anticonvulsant activity of organic mono- and di-cations and
      their potential to inhibit NMDA and AMPA glutamate receptors].
AB  - Effects of mono- and dicationic derivatives of adamantine and phenylcyclohexyl
      were studied on: (i) open channels of NMDA and AMPA glutamate receptors in the
      experiments on the isolated rat brain neurones, and (ii) convulsions induced by
      intraventricular injections of NMDA or kainate in mice. Monocations inhibited the
      NMDA receptors in vitro and prevented convulsions induced by NMDA in vivo, but
      failed to affect both the AMPA receptors and kainite-induced convulsions.
      Dications (IEM-1754 and IEM-1925) revealed both anti-NMDA and anti-AMPA potency
      in vitro, were highly effective against kainite-induced convulsions and excelled
      monocations in preventing the NMDA-induced ones. Evidently some steps connected
      with the AMPA receptor activity are involved in the genesis of the NMDA-induced
      convulsions. Anticonvulsant potency of IEM-1754 and IEM-1925 is comparable with
      those of known NMDA receptor inhibitors: memantine and MK-801. The IEM-1754 and
      IEM-1925 show no side effects. An incomplete correspondence between the activity
      in vitro and in vivo found studying some derivatives, may be due to peculiarities
      of their pharmacokinetics.

PMID- 12503424
TI  - [The effect of the duration of adaptation to laboratory conditions on the passive
      avoidance reflex in rats].
AB  - Influence of adaptation degree in new conditions on the passive avoidance was
      studied. The short period of habituation (3 days) positively influenced the rats'
      ability for memory trace retrieval. A negative correlation between the step
      through latency and anxiety in the elevated plus-maze, was shown. Prolongation of
      adaptation up to 9 days reduced levels of anxiety and retrieval of conditioned
      response. Modulating role of adaptation degree causing various anxiety levels in
      passive avoidance, is discussed.

PMID- 12503425
TI  - [The effect of the synthetic analogue of gonadoliberin on immune response and
      factors of nonspecific resistance in rats and mice].
AB  - Gonadotropin-releasing hormone's synthetic analogue (surfagon) injected
      intraperitoneally exerted a dose-dependent influence on humoral immune response
      values in rats and on phagocytic and functional activity of neutrophiles in mice.
      Castration induced a reliable decrease of the immune response and character. It
      may be concluded that the surfagon effect is not mediated by steroids.

PMID- 12503426
TI  - [Activity of the nucleolar organizers in cultured cells from the bone marrow
      erythroblastic islets].
AB  - The erythroblast islands of the bone marrow are the morphofunctional units of
      erythropoiesis. In this work, the functional state of erythroblast islands' cells
      of the bone marrow for the first time was defined by estimation of the activity
      of the nucleolar organizers of erythroid cells in the erythroblast islands
      cultivated during 24 and 48 hours in presence of various doses of erythropoietin.
      The findings indicated that an increase in doses of erythropoietin was
      accompanied by a corresponding increase of the activity of nucleolar organizers
      in erythrokaryocytes of erythroblast islands. The nucleolar organizers of
      erythroid cells in cultures of erythroblast islands responded with activation to
      very small doses of erythropoietin; besides, a proliferative response of
      erythrokaryocytes was observed after activation of the nucleolar organizers.

PMID- 12503427
TI  - [The effect of humoral factors on phagocytic activity of central macrophages in
      the erythroblast islet culture].
AB  - A 24-hour cultivation of erythroblast islets (El) in presence of erythropoietin
      (EP) and macrophage colony stimulating factor (MCSF) led to a concentration
      dependent enhancement of phagocytic activity (PA) of the El's "central"
      macrophages. The latter phenomenon was revealed in "mature" El classes only. The
      PA of "central" macrophages in "proliferating" El appeared to be affected neither
      by EP, nor by MCSF.

PMID- 12503428
TI  - [Study of NO action on calcium-activated potassium channel of the rat artery
      smooth muscle cells].
AB  - Nitric oxide (NO) released from the endothelium or from NO-donors is a powerful
      vasodilator. Its effect is mediated partly by vascular smooth muscle high
      conductance calcium-activated potassium (Kca) channels. Contradictory data exist
      as to whether NO activated the KCa channel directly or indirectly via protein
      kinase G (PKG). Thus the hypothesis that NO-donors can activate the KCa directly
      was investigated using the patch-clamp technique and freshly isolated smooth
      muscle cells from the rat tail artery. In inside-out experiments, the activity of
      KCa-channels was increased 1.61 +/- 0.20-fold (n = 10) by 10 microM SNP and 1.45
      +/- 0.17-fold (n = 8) by 10 microM SNAP. However, the activity of KCa channels
      was also increased 1.46 +/- 0.20-fold (n = 8) by addition of the experimental
      bath solution. Thus these results suggest that NO released from NO-donors cannot
      activate KCa channel of the rat tail artery smooth muscle cells directly.

PMID- 12503429
TI  - [Transmural pressure in the right atrium during positive pressure respiration in
      cats].
AB  - The influence of continuous positive pressure breathing (cm H2O) on the breathing
      mechanics, central venous pressure, and transmural pressure in the right atrium,
      were studied in anaesthetised cats separately during inspiration and expiration.
      It's shown that hemodynamics effects are directly connected with the influence of
      increased intrathoracic pressure during whole breathing cycles in contrast with
      the phase changes in natural expiration and inspiration. The inversion of
      relation of intrathoracic and central venous pressure due to displacement of the
      mechanical respiratory characteristics became the factors defining the fall of
      the right atrium filling pressure.

PMID- 12503430
TI  - [Adaptive behavior of active and passive rats after intranasal administration of
      the corticotropin-releasing hormone].
AB  - Behavioural effect of intranasal application of corticotropin-releasing hormone
      (CRH) was investigated in rats with high (KHA) and low (KLA) rate of learning in
      "open field" and plus-maze (PM) active avoidance test. The neurohormone provoked
      the opposed changes in behaviour of rats of this strain in both tests. The level
      of locomotion and exploratory activity rose in KLA rats and decreased in KHA
      rats. After the CRH application, the KLA rats but not KHA rats spent more time in
      the opened alleys of the PM than the control animals. The same behavioural
      changes were observed in our previous research when CRH was injected in striatum.
      We suppose that CRH is an endogenous factor of precise correction of the adaptive
      behaviour.

PMID- 12503431
TI  - [Effects of thyroxine and dexamethasone on kinetic characteristics of the small
      intestine enzymes in rat pups following a low-protein diet in female rats during
      lactation].
AB  - It is shown, that the value of Km for maltase, alkaline phosphatase,
      aminopeptidase M and glycyl-L-leucinedipeptidase, prepared from the jejunum and
      ileum of 10-day rat litter in membrane and soluble forms in most cases differed
      but a little in control animals and the rat litter whose mothers in the period of
      lactation had a diet with 2.5-fold reduced content of protein, and did not change
      under action of injected thyroxin and dexamethasone. It may be assumed that in
      the given experimental conditions each of the investigated digestive hydrolases
      in membrane and soluble forms represents the same enzyme. In conditions of the
      protein insufficiency in lactating females diet and under action of exogene
      hormones, apparently, no significant changes occur in structure of synthesised
      enzymes.

PMID- 12503432
TI  - [The chimpanzee heart rate in different emotional conditions in the course of a
      purposeful activity].

PMID- 12503433
TI  - Otitis media: old problem, new problem.

PMID- 12503434
TI  - A 13-year-old boy with recurrent syncopal episodes.

PMID- 12503435
TI  - What's new in the diagnosis and management of otitis media?

PMID- 12503436
TI  - Therapeutic nihilists: lend me your ears, or the witches' cauldron of acute
      otitis media.

PMID- 12503437
TI  - Antibiotic resistance and choice of antimicrobial agents for acute otitis media.

PMID- 12503438
TI  - Vaccination for the prevention of acute otitis media: proof of concept and
      current challenges.

PMID- 12503439
TI  - Surgical management of otitis media.

PMID- 12503440
TI  - Changes in management of otitis media: 2003 and beyond.

PMID- 12503441
TI  - [Functional specifics of cortical associative regions participating in learning
      to differentiate visual information in monkeys].
AB  - In 3 groups of monkeys: intact, those with their 7th field bilaterally removed,
      and those with bilateral removal of the sulcus principalis, functional specifics
      of the cortex' associative areas were studied. Removal of the 7th field
      practically does not affect processes of training for images with such features
      as spatial frequency, colour, and images of animals, but considerably impairs the
      learning characteristics in visual differentiation of objects' size and spatial
      interrelationships among objects. Removal of the sulcus principalis considerably
      impairs the characteristics of differentiation of objects' size and spatial
      interrelationships among them, as well as differently coloured stimuli. In both
      these groups, the stable motor response term and the probability of refusal
      increase. The data obtained suggest that the sensory processing results in
      forming a few (at least three) functional visual informational flows with which
      different cortical areas operate.

PMID- 12503442
TI  - [Correcting effect of the locus coeruleus on ophthalmic hypertension of the
      hypothalamic genesis].
AB  - We studied the intraocular pressure and the humor aquosus volume changes after a
      chronic emotional stress produced by a prolonged electrical stimulation of the
      multiple ventromedial (VMHN) hypothalamic nuclei and the locus coeruleus. The
      VMHN stimulation caused an increase in the intraocular pressure and production of
      the humor aquosus, as well as a decrease in the outflow ratio. Stimulation of the
      locus coeruleus increased the intraocular pressure to a lesser extent. A combined
      effect of both types of stimulation normalised the intraocular pressure due to a
      decrease in the humor aquosus production, the outflow ratio remaining unchanged.

PMID- 12503443
TI  - [Effect of transcranial electric stimulation on the adaptation state].
AB  - The influence of transcranial electrostimulation was studied in medical students
      considering their adaptation response type (training, activation, stress),
      reactivity level, psycho-physiological and vegetative status. The transcranial
      electrostimulation was effective in subjects with the adaptation response
      involving training and activation, and had no effect when stress was combined
      with vagotonic prevalence. The transcranial electrostimulation assists to
      improvement of the students' psycho-physiological indexes and to increase of
      their reactivity level.

PMID- 12503444
TI  - [Nitric oxide in the lymphatic microvessel regulation].
AB  - Topical application of sodium nitroprusside on rat mesentery has a marked
      influence on lymph microvessels function. The drug causes a dilation of majority
      of lymphangions and decrease of the pacemaker activity of the vessel wall
      structures and valves. These changes do not lead to lymph stasis, and lymph flow
      velocity does not reduce. The non-selective inhibitor of NO synthase (N-nitro-L
      arginine) intensifies vasomotions of lymph microvessels, modulates phasic
      contractile activity and increases lymph flow velocity. There is a time dependent
      dynamic of changes in action of N-nitro-L-arginine. During inhibition of
      endogenous NO synthesis the responses of lymph microvessels on sodium
      nitroprusside application are modified: the constriction of majority lymphangions
      and activation of valve work are observed.

PMID- 12503445
TI  - [Hematologic and various immunologic parameters of the body response in
      experimental epileptogenesis].
AB  - The aim of present study was to reveal the figures that show the organism
      reactivity at various stages of the amygdala kindling. We found that a completed
      kindling formed by stimulation of the piriform cortex, is accompanied by systemic
      changes in white and red blood. First stages of kindling during the cortical
      nucleus stimulation are characterised by reactive changes of erythrocytes and
      thrombocytes suggesting that changes occur in the homeostasis. We discuss
      possible mechanisms of these changes.

PMID- 12503446
TI  - [Response of respiratory neurons of the medulla oblongata to the septum
      stimulation in hypoxia].
AB  - In the oxygen deficiency conditions, we studied influence of irritation of
      ventral (BNST), lateral (LSN) and medial (MSN) nuclei of the septum on the
      impulse activity of the bulbar respiratory neurons and on respiration. Phases of
      hypoxia were the model of experiment. In conditions of normal atmospheric
      pressure, the electrical stimulation of BNST, LSN and MSN nuclei of the septum
      exerted inhibiting as well as activating influence with the inhibiting influence
      prevailing. In difficult conditions of hypoxia (7.5-8 thousand meters) on the
      reduction of the impulse activity of neurons, stimulation of septum nucleuses
      induced uncharacteristic reactions of those neurons.

PMID- 12503447
TI  - [Participation of the brain catecholamines in changes in activity of the rat
      hypophyseal-adrenal system induced by hydrocortisone administration during
      neonatal ontogenesis].
AB  - Administration of hydrocortisone or 6-hydroxydopamine (6-ONDA) to little rats
      from the 1st to the 5th day of life affected functional activity of the
      hypophyseal-adrenal system (HAS) of immature rats. In the morning hours, the rats
      developed a decrease in the basal and stressor levels of corticosterone in the
      blood, whereas administration of the 6-ONDA did not change the functional
      activity of the HAS in the morning. The data obtained suggest that disorders in
      the HAS regulation by the feedback mechanism resulting from neonatal
      administration of hydrocortisone may be associated with a drop in the
      noradrenaline level in the hypothalamus.

PMID- 12503448
TI  - [Bile secretion in the liver caused by verapamil].
AB  - Verapamil was studied for its effects on secretory function of liver in rats. In
      the animals with low initial level of bile secretion, infusion of verapamil
      resulted in increase of the bile flow conjugated with taurine bile salts and
      ester of cholesterol, and in reduction of the non-conjugated bile salts
      secretion, as well as bile salts conjugated with glycine. In the animals with
      high initial level of the liver secretory function, verapamil decreased the bile
      flow, the secretion of unconjugated bile salts, and bile salts conjugated with
      taurine and glycine, phospholipids, cholesterol and its ester. The changes of
      bile flow and biliary secretion of bile acids and lipids in two groups of animals
      suggest that verapamil could be influenced in regulation of bile secretion
      depending on its initial level. Possible mechanisms of the bile secretion
      regulation by verapamil, are discussed.

PMID- 12503449
TI  - [Mechanism of the serotonin effect on motility of the duodenum, ileum, and
      jejunum in awake rabbits].
AB  - I. v. administration of serotonin to alert rabbits produced a phasic change of
      contractile activity of duodenum, ileum, and jejunum including excitatory and
      inhibitory components. It is shown that stimulation of the small bowel motility
      is caused by serotonin activation of non-cholinergic excitatory mechanism with
      participation of effector cholinergic neurones. The initial suppression of the
      motility is caused by participation of nonadrenergic noncholinergic inhibitory
      mechanism, and the secondary inhibition of contractile activity of a small bowel
      with serotonin has an adrenergic nature.

PMID- 12503450
TI  - [Delayed effects of protein deficiency in nutrition of the pregnant rats on
      development of the enzymatic system in digestive and nondigestive organs of
      offspring].
AB  - It has been found for the first time that protein deficit in female's nutrition
      during prenatal development of the offspring is accompanied by considerable
      changes in the activity of intestinal digestive enzymes and of the same
      hydrolases in the colon, liver and kidneys both in early and in late ontogenesis.
      It seems possible that changes of the small intestine enzyme functions and
      hydrolytic functions of other digestive and non-digestive organs in result of an
      unfavorable early "metabolic/nutritional programming" may be crucial in disorders
      of metabolic processes leading to development of diseases of risk in adult life.

PMID- 12503451
TI  - [Functional distinction of secreting pools of the pancreas and participation of
      the pancreatic ductal system in the development of the pancreatic secret
      properties].
AB  - Acute experiments on dogs with separate secretion of the pancreatic enzymes,
      either stimulated or inhibited, from two lobes of pancreas, and investigation
      into the character of kinetics of the secretion from 5-7 ductal pools of the
      pancreas showed the functional specifics, with the device of ductal valves and
      microdepot of a secret of the pancreas ductal system playing an important role.
      The conclusion is made that the final secret of pancreas removed to the duodenum
      is a product of a secret-motor activation of non-equipotentional microregions of
      the gland, being the components of an intervisceral dynamical mosaic.

PMID- 12503452
TI  - [Scientific studies at the Department of Physiology of the Military Medical
      Academy].

PMID- 12503453
TI  - [History of the Pavlovian digestive physiology].

PMID- 12503454
TI  - Complementary and alternative therapies and SCI nursing.
AB  - Increasing numbers of individuals are experimenting with different complementary
      and alternative techniques and practices in their quest to improve their health
      status or change symptom experiences. Consumer utilization patterns are
      described, activities to ensure the safety and efficacy of alternative practices
      are reviewed, and relationships to nursing interventions and nursing
      responsibilities are presented. The relationship between
      complementary/alternative therapies and spinal cord injury (SCI) nursing
      practice, education, and research are described, as well as strategies for
      integrating these therapies into SCI nursing. The potential roles for SCI nurses
      and benefits to individuals with SCI are unlimited.

PMID- 12503455
TI  - Integration: a synergistic approach to health/wellness.
AB  - Integration is defined as the weaving of new possibilities, new alternatives, and
      new options into a cloak of security where concepts of health or wellness are
      actualized. In integration, the mind, body, and soul are open to explore and
      embrace these new possibilities, alternatives, and options. The authors believe
      the process of integration, and thus health, is enhanced via synergy;
      particularly the synergy created by the provider/individual relationship. Health
      care is an outcome or the culmination of a variety of modalities identified,
      explored, and celebrated by the individual seeking health/wellness and the
      primary care practitioner coordinating care. In the quest to provide individuals
      with the health care they seek, practitioners are encouraged to take note of the
      lessons taught by alternative and complementary health care practitioners.
      Individuals want to be heard. They are seeking effective, low cost interventions
      that are as natural as possible. Reiki, meditation, biofeedback, massage,
      botanicals, healing touch, ayurveda, and aromatherapy represent some of the
      healing modalities and complementary therapies to explore for integration.

PMID- 12503456
TI  - Learning styles and teaching strategies: enhancing the patient education
      experience.
AB  - Enhancing the effectiveness of patient education efforts is a key goal for any
      health care provider involved in patient care. Nurses have limited time to review
      many important topics of education for patients in the rehabilitation process.
      Assessing the learning style of patients and then focusing teaching strategies to
      meet those individual styles can increase motivation, improve retention, and make
      the teaching-learning session more effective. This article will provide the
      reader with some practical information, usable tools, and additional resources to
      meet Joint Commission on Accreditation of Healthcare Organizations (JCAHO)
      standards and improve the delivery of patient education. Nurses attuned to the
      individual needs of patients, including learning styles, will find that this
      article has important information that can be applied to the clinical setting.

PMID- 12503457
TI  - Health care in Cuba: socialized medicine in a developing country.
AB  - Several registered nurses representing the American Organization of Nurse
      Executives (AONE), the American Association of Critical Care Nurses, and a group
      of nurses and physicians representing Disease Case Management visited Cuba under
      the auspices of the People to People Ambassador Program. The purpose of the
      People to People Ambassador Program is to exchange ideas, foster international
      friendships, and advance worldwide peace and communication. The authors were a
      part of the AONE delegation and will share their experiences during their visit
      to Cuban health care facilities.

PMID- 12503458
TI  - Moving from distress to de-stress: some suggestions on managing the stress in
      your life.

PMID- 12503459
TI  - A path less traveled: nursing the spirit.

PMID- 12503460
TI  - Technological developments in urethral catheters.

PMID- 12503461
TI  - Avoiding pitfalls in APA style.

PMID- 12503462
TI  - Embracing diversity.
AB  - It is imperative that nursing professionals are proactive, as well as creative,
      when addressing overall nursing workforce planning and the nursing shortage. The
      profession must take a comprehensive look at what is currently available to
      manage an increasingly complex health care system that manages care for more
      acutely ill and chronically ill/impaired patients. Being proactive, open-minded,
      and flexible may help nurses make strides in increased staffing of all of our
      health care agencies. Embracing a more diverse workforce is one powerful
      mechanism toward that goal.

PMID- 12503463
TI  - Transition to adult care.

PMID- 12503464
TI  - CARF: symbol of rehabilitation excellence.

PMID- 12503465
TI  - Who should teach advanced practice nursing?

PMID- 12503466
TI  - Students take the professor home.
AB  - The nursing process is used to provide a rationale for substituting formal
      lectures on maternal-child nursing theory with audiotapes included in
      instructional packages provided to students prior to scheduled classroom time.
      Five objectives for this teaching strategy are presented and evaluated. Although
      test scores were not used for evaluation, students were found to listen to the
      tapes and benefit from the experience. Faculty used classroom time to reinforce
      content with active learning methods. The audiotaped lectures and handouts were a
      form of distributed learning, which provided more time for faculty-student
      interaction and reinforcement of pertinent concepts.

PMID- 12503467
TI  - Reflections on caring narratives: enhancing patterns of knowing.
AB  - The purpose of this study was to provide graduate students with the opportunity
      to enrich their esthetic knowing and acquire the meaning of caring in their
      practice by reflecting on their caring narratives. Content analysis examining for
      context, process, and fulfillment was used to analyze 68 caring encounters
      written by five classes of graduate nursing students over five semesters of
      course work. This article focuses on the value of reflection in knowing and the
      fulfillment identified by the students through the reflective process. Student
      fulfillment included reflecting on the need to care for self, knowing that
      emotional attachment can be dangerous, recognizing caring as a moral
      responsibility, attending to caring teaches one about caring, and reflecting on
      caring encounters engages one in defining caring. It is concluded that graduate
      nursing students can enhance multiple ways of knowing and their understanding of
      caring through the process of reflecting on caring encounters.

PMID- 12503468
TI  - RN-MSN admission practices and curricula in the mid-Atlantic region.
AB  - Nurse educators are increasingly sensitive to the differences in learning needs
      of adult students in comparison to the traditional generic student and to the
      demand for advanced practice nurses. For these reasons, the number and type of
      accelerated programs has increased. There is very little in the literature
      related to RN-MSN programs. To determine the state of RN-MSN education, a
      descriptive exploratory study was conducted to examine admission and curricular
      requirements for RN-MSN nursing programs in the mid-Atlantic region. The findings
      reveal a wide variety of educational practices. Over 74 percent of responding
      programs indicated that challenge exams are used to accelerate students'
      progress; 59 percent reported participating in statewide articulation agreements.
      Credit requirements for core and major courses were found to vary dramatically,
      as do credits required to earn the BSN-MSN credential; the average number of
      credits for program completion was 127. GPA requirements for admission ranged
      from 2.5 to 3.5. Findings from this study can assist existing programs to assess
      their comparability and help developing programs understand emerging patterns in
      RN-MSN education.

PMID- 12503469
TI  - The legalities and practicalities of developing a course-specific electronic
      reserve room.
AB  - This article discusses important issues related to maintaining the currency of
      readings in a nursing course. The development of a course-specific electronic
      reserve room is offered as a methodology for achieving both timeliness and
      simplified distribution of course readings. The article reviews legal issues
      related to the development of an electronic reserve room for internet access. In
      addition, hardware and software issues related to the transference of paper
      materials to a digital format are considered.

PMID- 12503470
TI  - Position statement. Funding for nurse education research.

PMID- 12503471
TI  - Magnesium in acute myocardial infarction?

PMID- 12503472
TI  - [Why heart failure clinics?].

PMID- 12503473
TI  - [The concept of soul in the course of history. Thoughts on psyche, mind and
      awareness].
AB  - This paper seeks to convey an insight into the interrelationships between body,
      soul and mind and to show how the concept of "soul" has evolved through the
      course of history. In German the word "soul" has a confusing array of meanings
      today. For most of us it comprises all of man's emotions, his awareness,
      constructive thought, drive, state of mind and spirit. The soul thus represents
      the essence of a person and his relationships to those closest to him. For many
      people the soul was and still is the principle of life, the breath of life and
      the force of life. The immortal soul escapes, leaves the body, is weighed and
      judged. At all times in history man has doggedly pursued the mysteries of self
      awareness, the ultimate truth and the soul. What he found varied, depending on
      the age and the place. What the Hebrew Bible and the New Testament express in
      deep-seated metaphors, the Greek philosophers put into clear-cut words: their
      concept of soul was then largely integrated into Christian thought. Meister
      Eckhart describes the soul in mystically transfigured passion. C.G. Jung writes
      of the "animus and anima." Sigmund Freud uses the term "psyche." Radical
      materialism denies the existence and independence of the soul's processes. The
      questions where we come from and where we are going, why and what for, no longer
      find a common answer. Psychiatry, however, takes up the intellectual call of the
      time and replies to the challenges of the day. Thus, the search for the "soul", a
      search that occupies so many people, also always involves the search for the
      whole person.

PMID- 12503474
TI  - [Adaptation of guidelines for the treatment of chronic heart failure in a
      specialized heart failure clinic].
AB  - BACKGROUND: Chronic heart failure is associated with high mortality and
      morbidity. In spite of a number of trials showing significant improvement in
      survival and reduction in hospitalization for patients who received ACE
      inhibitors/AT1 receptor antagonists (ACEI/ARB), beta-blockers and spironolactone,
      and notwithstanding the recommendations of national and international guidelines
      for the management of heart failure, substantial proportions of patients are not
      receiving this treatment. The aim of our study was to analyse 1. the efficiency
      of a specialized heart failure clinic in translating guidelines into clinical
      practice, and 2. the effect of optimized neurohormonal therapy on patient
      outcome. METHODS AND RESULTS: The data of patients with systolic heart failure
      and an ejection fraction < or = 35% referred to the Innsbruck Heart Failure and
      Transplantation Program between February 2000 and October 2001 were analysed. The
      number of patients treated with ACEI/ARB, beta-blocker and spironolactone
      increased significantly in the investigation period (p < 0.05). Equivalent dose
      for captopril and bisoprolol per patient developed from 66.4 +/- 42.8 to 96.5 +/-
      41.9 mg (p < 0.001) and from 2.0 +/- 2.9 to 6.3 +/- 4.0 mg (p < 0.001),
      respectively. Optimization of neurohormonal therapy was associated with a
      significant improvement in NYHA class (2.5 +/- 0.8 vs. 1.9 +/- 0.8; p < 0.001).
      No relevant changes were noticed for blood pressure, serum creatinine, serum
      sodium, and serum potassium, whereas heart rate dropped significantly. Kaplan
      Meier curves examining the time to first event of the combined end point of
      mortality and hospitalisation for worsening heart failure revealed a clear
      benefit for patients on combined neurohormonal therapy (ACEI/ARB and beta
      blocker, n = 86) when compared with patients on neurohormonal monotherapy
      (ACEI/ARB or beta-blocker, n = 35), (p < or = 0.001). Differences remained
      significant (p = 0.022) after adjusting for NYHA class at referral, age, gender,
      etiology of the underlying cardiomyopathy, ejection fraction, and atrial
      fibrillation in Cox regression analysis. CONCLUSION: Guidelines for the
      management of chronic heart failure patients can be translated efficiently into
      clinical practice by a specialized heart failure clinic. Optimization of therapy
      is associated with an improvement in functional status and a decrease in
      mortality or hospitalization for worsening heart failure. Therefore the
      nationwide installation of specialized heart failure clinics is required.

PMID- 12503475
TI  - Effect of prickly pear (Opuntia robusta) on glucose- and lipid-metabolism in non
      diabetics with hyperlipidemia--a pilot study.
AB  - BACKGROUND: Besides others pectin, a soluble fibre, has been reported to be
      effective in lowering cholesterol levels in both animals and man with
      hyperlipidemia as well as being able to slow carbohydrate absorption and hence
      reduce the postprandial rise in blood glucose and serum insulin in patients with
      type-II diabetes. Aim of this pilot study was to assess the effect of prickly
      pear consumption on glucose- and lipid metabolism. DESIGN: In 24 non-diabetic,
      non-obese males (aged 37-55 years) suffering from primary isolated
      hypercholesterolemia (n = 12; group A) or combined hyperlipidemia (n = 12; group
      B) respectively, the influence of prickly pear pectin (Opuntia robusta)-intake on
      glucose- and lipid metabolism was examined. After an 8 week pre-running phase
      with a 7506 KJ step-I diet (phase I), 625 KJ were replaced by prickly pear edible
      pulp (250 g/day) for 8 further weeks (phase II). RESULTS: Prickly pear leads to a
      decrease of total cholesterol (12%), low-density lipoprotein-cholesterol (15%),
      apolipoprotein B (9%), triglycerides (12%), fibrinogen (11%), blood glucose
      (11%), insulin (11%) and uric acid (10%), while body weight, high-density
      lipoprotein-cholesterol, apolipoprotein A-I, and lipoprotein(a) remained
      unchanged. CONCLUSION: The hypocholesterolemic action of prickly pear may be
      partly explained by the fibre (pectin) content, but the hypoglycaemic actions
      (improvement of insulin sensitivity) in the non-obese, non-diabetic need further
      investigation to get more insights on the potential advantage of treating the
      metabolic syndrome.

PMID- 12503476
TI  - [Manual compression versus mechanical compression device (FemoStop) after
      diagnostic coronary angiography with/without intervention].
AB  - BACKGROUND: The aim of our study was to evaluate the practicability and the
      complication rates of two different forms of the post-angiographic closure of the
      femoral artery. METHODS: We randomized 239 patients over a time period of 4
      months to either a mechanical compression system (FemoStop, 111 patients) or to
      conventional manual compression (128 patients). A Doppler-sonographic examination
      was performed if the patient reported pain of the puncture site, or if
      auscultation or palpation suspected a complication on the day after compression.
      RESULTS: After manual compression, Doppler-sonography had to be performed in 21
      patients (16.4%). In the FemoStop-group only 14 patients (12.6%, p = ns) had to
      be referred for ultrasound examination. A complication was detected in 13
      patients (10.1%) after manual compression and in 5 patients (4.5%, p = ns) after
      closure with the mechanical device. The incidence of a pseudo-aneurysma or of an
      arterio-venous fistula did not show any difference between the two groups. In 6
      patients of the manual compression group a hematoma was found (p < 0.05), whereas
      no hematoma occurred in the FemoStop-group. None of the hematomas required the
      infusion of blood concentrates or surgical correction. In one patient with
      extreme overweight the mechanical compression device could not be applied. The
      mechanical compression device was used successfully in patients who had received
      heparin, acetyl-salicyl-acid or a glycoprotein IIb/IIIa receptor antagonist and
      in whom a significantly longer compression time and higher complication rate
      could have been expected. In addition, post-angiographic closure with the was
      less time consuming for the staff involved. In contrast, the higher cost of the
      mechanical compression device presents a disadvantage. CONCLUSION: A mechanical
      compression device (FemoStop) can be used successfully in routine post
      angiographic management and shows a trend to lower complication rates than manual
      compression and increased acceptance by patients and physicians. However, the
      overall costs are higher for the mechanical compression device.

PMID- 12503477
TI  - Endothelial cell activation and blood coagulation in critically ill patients with
      lung injury.
AB  - INTRODUCTION: Adult respiratory distress syndrome is a life-threatening disease
      that requires respiratory assistance. It is associated with endothelial cell
      damage, coagulation activation, and intravascular fibrin deposition. This
      prospective study was conducted to determine whether the plasma levels of
      specific markers of endothelial cell function and coagulation activation are
      related to the degree of pulmonary disturbance. PATIENTS AND METHODS: Fourteen
      patients (8 male, 6 female, median age 69 years), admitted to a medical intensive
      care unit with various stages of lung injury needing mechanical ventilation, were
      compared with 16 healthy age- and sex-matched control subjects. RESULTS: Markers
      of endothelial cell damage and coagulation activation were significantly elevated
      in patients with lung injury compared with controls: von Willebrand factor (vWF)
      4.12 vs. 1.25 U/ml, p < 0.0001; F VIII 4.40 vs. 1.88 U/ml, p = 0.0001; tissue
      type plasminogen activator (tPA) 11.6 vs. 8.7 ng/ml, p = 0.02; plasminogen
      activator inhibitor-1 (PAI) 48.9 vs. 14.6 ng/ml, p < 0.0001; D-dimer 2.9 vs. 0.6
      microgram/ml, p < 0.0001; thrombin-antithrombin III complex (TAT) 7.9 vs. 2.2
      ng/ml, p < 0.0001 (median values; Mann-Whitney U-test). vWF, tPA, PAI and D-Dimer
      were significantly correlated with the PaO2/FiO2 ratio (p = 0.0003, 0.003, 0.04,
      0.02, respectively; Spearman's rank correlation). CONCLUSION: These findings
      suggest that the endothelial cell disturbance and the activation of the
      coagulation system in patients with lung injury are related to the degree of
      pulmonary dysfunction.

PMID- 12503478
TI  - [Stabilization of proximal humeral fractures with the intramedullary dynamic
      titanium helix wire].
AB  - The implant Helix-Wire is a treatment device that is used since 1997. It provides
      minimally invasive stabilization of subcapital humeral fractures. The implant is
      inserted through a small lateral entrance and a cortical hole drilled into the
      intramedullary space of the proximal humeral shaft and drilled into the humeral
      head for fracture stabilization. After careful preoperative planning and
      successful repositioning of the fracture the technique can be performed without
      difficulty. A review of 35 patients with subcapital humeral fractures, who were
      operated using the titanium wire helix between 1998 and 2000, was carried out.
      Clinical and radiological results were documented. After an average time of 11.5
      months 13 patients were examined according to the Constant Score: 5 good or
      excellent, 4 fair and 4 bad results were achieved. We conclude that this implant
      provides sufficient stabilization of subcapital humeral fractures classified as
      AO 11 A2, 11 A3.1, 11A3.2, 11B1.1, 11B1.2. It does not offer an advantage for the
      treatment of unstable fractures with multiple fragments or cancellous bone
      deficiency (11 A3.3, 11 B2.2, 11 B2.3).

PMID- 12503479
TI  - Microsurgery for glioblastoma preserves short-term quality of life both in
      functionally impaired and independent patients.
AB  - OBJECTIVE: Considering the short remaining life expectancy with glioblastoma
      multiforme, numerous patients and their referring physicians are hesitant to use
      aggressive surgical treatment for fear of greater risk of neurological
      deterioration. The aim of our study was to determine whether surgical treatment
      of glioblastoma, utilizing modern microsurgical dissection techniques and tools,
      interferes with short-term quality of life. METHODS: The functional status before
      and after 67 microsurgical operations in 65 patients with glioblastomas was
      studied retrospectively. To evaluate the patients' quality of life, their
      functional neurological status was correlated with the Karnofsky performance
      scale (KPS). Post-operative evaluation was done within 7 days of surgery.
      RESULTS: No significant difference was found between the preoperative and the
      early postoperative functional status. Neither patient age nor the preoperative
      functional status determined a significant risk for postoperative functional
      deterioration. Patients with tumors involving so-called eloquent brain areas
      statistically worsened (p = 0.018); however, they showed only mild clinical
      impairment that was represented by a mean KPS status decline of less than -10.
      After total tumor resection, patients showed functional improvement. CONCLUSION:
      Microsurgery is safe and effective in order to improve or preserve short-term
      quality of life in glioblastoma patients. Total tumor resection is not associated
      with a significantly greater risk for neurological deterioration, either in
      patients with preoperative functional impairment, or in functionally independent
      patients.

PMID- 12503480
TI  - Management of respiratory deterioration in a pregnant patient with severe
      kyphoscoliosis by non-invasive positive pressure ventilation.
AB  - The problem of kyphoscoliosis in combination with pregnancy is uncommon and
      published cases are rare. Until now, little and controversial information on the
      outcome, optimal management and course of pregnancy in patients with
      kyphoscoliosis has been available. The majority of maternal deaths seem to be
      attributed to cardiorespiratory failure, while obstetric complications account
      for relatively few complications. We present the case of a 34-year old pregnant
      woman with congenital kyphoscoliosis and a forced vital capacity (FVC) of about
      one liter. A further deterioration of lung function was expected. In fact, severe
      limitations in exercise capacity (bed rest), fatigue and hypersomnolence, as well
      as a severe increase in pulmonary hypertension occurred during the second and
      third trimester. Nasal intermittent positive pressure ventilation (NIP-PV) with
      bilevel positive airway pressure (BiPAP) was started in the 20th week of
      gestation and adapted throughout pregnancy. Nasal BiPAP was well-tolerated and
      corrected exercise tolerance, fatigue and nocturnal oxygen desaturations. At 32
      weeks of gestation, the patient was admitted for an elective Caesarean section
      under combined spinal-epidural anaesthesia with ongoing NIPPV, and delivered a
      healthy baby. Home nocturnal ventilatory support was continued as nocturnal
      episodic desaturations were also assessed during the postpartum period. At time
      of discharge, the patient's exercise capacity and lung function were nearly equal
      to levels before pregnancy. We conclude that pregnancy in selected kyphoscoliotic
      patients with severe limitations in lung function is relatively safe for both the
      mother and the child when NIPPV is used for overcoming respiratory deterioration
      and for preventing further cardiorespiratory failure.

PMID- 12503481
TI  - [Euthanasia and the principle of the double action].

PMID- 12503482
TI  - The impact factor of Wiener klinische Wochenschrift.

PMID- 12503483
TI  - At the top of his lungs.

PMID- 12503484
TI  - Bye-bye, burgers.

PMID- 12503485
TI  - The new drug war.

PMID- 12503486
TI  - A daughter vaccine.

PMID- 12503487
TI  - A time before dying.

PMID- 12503489
TI  - Going to the dogs.

PMID- 12503488
TI  - Meet Mr. Danovic.

PMID- 12503490
TI  - Keeping secrets.

PMID- 12503491
TI  - Rogue medical records.

PMID- 12503492
TI  - Refuse treatment options: a case study.
AB  - Records in public archives were evaluated for the period 1981-1991. Simple
      surveys of peoples and of technology and physical premises provided insight to
      gauge the attitudes of a local community in the Melbourne municipality and the
      Melbourne City Council towards composting of organic waste materials. There is a
      lag in perception and attitudes between the local community and the local
      government towards composting of organic refuse as a solid waste treatment
      option. The simple methodology of the study still made it possible to verify past
      and present perceptions and attitudes.

PMID- 12503493
TI  - Integrated economic-ecological analysis and evaluation of management strategies
      on nutrient abatement in the Rhine basin.
AB  - Management of river basins involves the making of informed choices about the
      desired levels of economic activities and ecosystem functioning in the catchment.
      Information on the economic and ecological effects of measures as well as their
      spatial distribution is therefore needed. This paper proposes the following
      instruments to support decision-making in river basins: (1) the linking of models
      and indicators to describe the economic and ecological effects of management
      actions and their spatial distribution and (2) an extended evaluation framework
      that aims to evaluate management actions on three objectives for sustainable
      river management. These are cost-effectiveness, spatial equity, and environmental
      quality. This paper illustrates the potential of these instruments for river
      basin management by a case-study on nutrient management in the Rhine basin. In
      this case-study four nutrient abatement strategies are formulated, based on
      policies of the International Commission for the Protection of the Rhine and the
      North Sea Commission. These strategies are analysed and evaluated on their
      contribution to the three management objectives. Results show that none of these
      strategies score highest on cost-effectiveness, spatial equity and environmental
      quality simultaneously. It appears that cost-effectiveness is in conflict with
      environmental quality, whereas spatial equity and cost-effectiveness show quite
      close correspondence. This means that a trade-off has to be made between costs
      and spatial equity on the one hand, and environmental standards on the other
      hand. This paper offers a framework to make these trade-offs more explicit and
      provides quantitative information on cause-effect relationships, economic and
      environmental effects and the spatial distribution of these effects for various
      management strategies. This information can be particularly useful in the
      development of compromises required to establish international agreement and co
      operation.

PMID- 12503494
TI  - Modeling the relationship between land use and surface water quality.
AB  - It is widely known that watershed hydrology is dependent on many factors,
      including land use, climate, and soil conditions. But the relative impacts of
      different types of land use on the surface water are yet to be ascertained and
      quantified. This research attempted to use a comprehensive approach to examine
      the hydrologic effects of land use at both a regional and a local scale.
      Statistical and spatial analyses were employed to examine the statistical and
      spatial relationships of land use and the flow and water quality in receiving
      waters on a regional scale in the State of Ohio. Besides, a widely accepted
      watershed-based water quality assessment tool, the Better Assessment Science
      Integrating Point and Nonpoint Sources (BASINS), was adopted to model the
      plausible effects of land use on water quality in a local watershed in the East
      Fork Little Miami River Basin. The results from the statistical analyses revealed
      that there was a significant relationship between land use and in-stream water
      quality, especially for nitrogen, phosphorus and Fecal coliform. The geographic
      information systems (GIS) spatial analyses identified the watersheds that have
      high levels of contaminants and percentages of agricultural and urban lands.
      Furthermore, the hydrologic and water quality modeling showed that agricultural
      and impervious urban lands produced a much higher level of nitrogen and
      phosphorus than other land surfaces. From this research, it seems that the
      approach adopted in this study is comprehensive, covering both the regional and
      local scales. It also reveals that BASINS is a very useful and reliable tool,
      capable of characterizing the flow and water quality conditions for the study
      area under different watershed scales. With little modification, these models
      should be able to adapt to other watersheds or to simulate other contaminants.
      They also can be used to study the plausible impacts of global environmental
      change. In addition, the information on the hydrologic effects of land use is
      very useful. It can provide guidelines not only for resource managers in
      restoring our aquatic ecosystems, but also for local planners in devising viable
      and ecologically-sound watershed development plans, as well as for policy makers
      in evaluating alternate land management decisions.

PMID- 12503495
TI  - Electronic labelling in recycling of manufactured articles.
AB  - The concept of a recycling system aiming at the recovery of resources from
      manufactured articles is proposed. The system integrates electronic labels for
      product identification and internet for global data exchange. A prototype for the
      recycling of electric motors has been developed, which implements a condition
      based recycling decision system to automatically select the environmentally and
      economically appropriate recycling strategy, thereby opening a potential market
      for second-hand motors and creating a profitable recycling process itself. The
      project has been designed to evaluate the feasibility of electronic
      identification applied on a large number of motors and to validate the system in
      real field conditions.

PMID- 12503496
TI  - An approach to integrated ecological assessment of resource condition: the Mid
      Atlantic estuaries as a case study.
AB  - The complex and interconnected nature of ecological systems often makes it
      difficult to understand and prevent multiresource, multistressor problems. This
      article describes a process to assess ecological condition at regional scales.
      The article also describes how the approach was applied to the Mid-Atlantic
      estuaries, where it focused on characterizing the current state of the
      environment rather than on predicting future effects from humans. The necessity
      for iteration during the exercise showed how important it was to identify the
      purpose of the assessment and its users, that appropriate, consistent data are
      lacking for large-scale assessments, and that it remains a challenge to
      communicate succinctly the results of such an assessment.

PMID- 12503497
TI  - Capital assets and intercultural borderlands: socio-cultural challenges for
      natural resource management.
AB  - In their design or implementation, many natural resource management (NRM)
      programs ignore critical socio-cultural dimensions of the challenge to advance
      sustainability. Building on particular ideas about culture and human ecosystems,
      we combine the strengths of the capital assets model of sustainability and the
      idea of intercultural borderlands to respond to this gap. To advance our thesis
      about the utility of these tools, we critically reviewed and analysed a cross
      disciplinary literature relating to the socio-cultural dimensions of NRM. This
      paper stems from that labour and examines particular tensions that arise in land
      management as a result of Australians' specific colonial and postcolonial
      legacies. These tensions--related to ethnicity, gender, population, age and
      health--are among the threads in the larger tapestry that comprises the socio
      cultural dimensions of NRM. For the Australian case, they are central,
      longstanding and persistent, and thus worthy of analysis; and they are applicable
      in general terms to other places with similar histories of settlement and land
      use.

PMID- 12503498
TI  - Starting point or solution? Community-based marine protected areas in the
      Philippines.
AB  - In 1985, in response to declining coral reef conditions, local residents and
      officials established small, no-take marine sanctuaries on Balicasag and
      Pamilacan Islands through a community-based process. The implementation of marine
      protected areas (MPAs) on Balicasag and Pamilacan Islands has been a partial
      success. As a direct result of protection, living hard coral cover has increased
      by 119% in Balicasag's sanctuary and by 67% in the non-sanctuary during the
      period 1984 to 1999, but Balicasag's reef is increasingly affected by breakage
      from anchors from dive boats and Crown-of-thorns starfish infestations. During
      the same period, living hard coral cover decreased by 20% in Pamilacan's
      sanctuary and by 45% in the non-sanctuary from 1984 to 1999. The decrease in
      living hard coral cover in Pamilacan's sanctuary is most likely a result of the
      1998 bleaching event, Crown-of-thorn starfish and possible storm damage. Although
      there was an initial increase in the economically important target fish abundance
      in the Balicasag sanctuary and non-sanctuary and in the Pamilacan sanctuary
      during the first two years of implementation in the mid-1980s, there has since
      been a significant decline. Mean target fish abundance for the Balicasag non
      sanctuary at 230 (+/- 65) individuals per 500 m2 is not significantly different
      from control sites without MPAs on nearby Panglao and Cabilao Islands at 164 (+/-
      67) individuals per 500 m2. In general, fish abundance and diversity inside and
      outside the sanctuaries peaked in 1986, a year after the establishment of the
      sanctuaries when enforcement was strictest. Therefore, despite considerable
      success in enforcing regulations associated with these small MPAs at Balicasag
      and Pamilacan Islands, a trend of declining fish abundance and species richness
      among economically valuable species immediately outside the no-take areas
      highlights the limitations of small and isolated MPAs. This study contributes to
      the growing sentiment that it is not realistic for scattered, small no-take areas
      to maintain fish abundance and diversity on surrounding reefs when intensive
      fishing effort immediately adjacent to no-take areas removes most fish that exit
      these areas. This finding emphasizes the importance of nesting individual MPAs
      within broader management regimes that lead to overall fishing effort reduction
      and networking of MPAs. Among other recommendations, the authors advocate for
      continued support for community-based MPAs, a network of MPAs, reduced fishing
      effort in areas surrounding the MPAs and other management measures to improve the
      quality of the coral reef habitats.

PMID- 12503499
TI  - A dynamic model for intertemporal allocation of old-growth forests in the Pacific
      Northwest.
AB  - Across the globe, continued policy debates regarding the management of old-growth
      forests center around the difficult task of balancing economic and ecological
      considerations. Though the forests of the Pacific Northwest United States are
      among the most studied old-growth ecosystems, ecological and economic analyses
      have yielded public land management directives that remain controversial.
      Specifically, the recently adopted Northwest Forest Plan lacks explicit goals for
      maintaining intergenerational equity for the use of forest resources and the
      diversity of old-growth ecosystems. Unlike previous studies which rely on
      monetary quantification of costs and benefits, this study develops and applies a
      conceptual framework for evaluating socially optimal Pacific Northwest old-growth
      forest utilization strategies. Conditions for the optimal management of old
      growth forests are derived using dynamic programming. The objective function
      synthesizes relevant biological and economic attributes of the old-growth
      allocation problem. Results in the form of extraction paths are compared given
      social pressure for consumptive and non-consumptive benefits, as well as
      different planning horizons, rates of social time preference, and environmental
      variance. Lengthening the planning horizon results in a vast divergence of
      optimal policies in the absence of discounting. Extraction rates appear to
      approach zero as the planning horizon approaches infinity. While higher rates of
      social time preference increase the rate of extraction, forest stocks remaining
      at the terminal time period equal levels remaining with a lower discount rate.
      Increasing environmental variance results in a higher level of stock remaining at
      the terminal time period. This analysis, while specific to the old-growth
      controversy of the Pacific Northwest, does provide general guidelines for
      addressing similar problems of multiple uses of natural areas, particularly where
      such uses are mutually incompatible, or where one use may be irreversibly
      destructive to another.

PMID- 12503500
TI  - Regional economic impacts of water management alternatives: the case of Devils
      Lake, North Dakota, USA.
AB  - Devils Lake, located in a closed basin in northeastern North Dakota has over a
      century-long history of highly fluctuating water levels. The lake has risen
      nearly 25 feet (7.7 m) since 1993, more than doubling its surface area. Rising
      water levels have affected rural lands, transportation routes, and communities
      near the lake. In response to rising lake levels, Federal, state and local
      agencies have adopted a three-part approach to flood damage reduction, consisting
      of (1) upper basin water management to reduce the amount of water reaching the
      lake, (2) protection for structures and infrastructure if the lake continues to
      rise, and (3) developing an emergency outlet to release some lake water. The
      purpose of this study was to provide information about the net regional economic
      effects of a proposed emergency outlet for Devils Lake. An input-output model was
      used to estimate the regional economic effects of the outlet, under two
      scenarios: (1) the most likely future situation (MLS) and (2) a best case
      situation (BCS) (i.e., where the benefits from the outlet would be greatest),
      albeit an unlikely one. Regional economic effects of the outlet include effects
      on transportation (road and railroad construction), agriculture (land kept in
      production, returned to production sooner, or kept in production longer),
      residential relocations, and outlet construction expenditures. Effects are
      measured as changes in gross business volume (gross receipts) for various
      sectors, secondary employment, and local tax collections. The net regional
      economic effects of the proposed outlet would be relatively small, and
      consideration of these economic impacts would not strengthen the case for an
      outlet.

PMID- 12503501
TI  - [HIV infection in adolescents living in developing countries].

PMID- 12503502
TI  - [Long-term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of
      infancy (Dravet's syndrome)].
AB  - OBJECTIVE: To describe the long term efficacy and tolerance of stiripentol
      associated with valproate and clobazam in an exhaustive cohort of patients with
      severe myoclonic epilepsy of infancy (Dravet's syndrome), in which short term
      efficacy of such a treatment has recently been demonstrated in a placebo
      controlled trial. RESULTS: In 46 patients the frequency and the duration of
      seizures was significantly reduced (p < 0.001) as well as the number of
      convulsive status at a median of three-year follow-up. Ten patients were
      dramatically improved (seizures significantly decreased in number [p = 0.002] and
      duration [p = 0.002] and status epilepticus disappeared), 20 were moderately
      improved (seizures significantly decreased in duration [p = 0.001] and status
      were less numerous), four had no response and efficacy was non evaluable in 12
      mainly because of adverse events. Efficacy was better in the youngest patients.
      The most frequent adverse events were loss of appetite and loss of weight. They
      could be so severe in patients over 12 years of age that the stiripentol dosage
      could not be increased to 50 mg kg-1 j-1. CONCLUSION: This follow-up study shows
      that stiripentol added to valproate and clobazam maintains its efficacy at long
      term in children with severe myoclonic epilepsy of infancy and suggests that the
      tritherapy should be introduced as early as possible in these patients in order
      to suppress the convulsive status epilepticus.

PMID- 12503503
TI  - [Mucolytic agents for acute respiratory tract infections in infants: a
      pharmacoepidemiologic problem?].
AB  - OBJECTIVE: To study the use of mucolytics agents, i.e. acetylcystein and
      carbocystein, in infants. To evaluate their efficacy and safety for their main
      indications. METHODS: A prospective one-day survey of prescriptions among 95
      office-based pediatricians. A systematic review of the literature. RESULTS: Among
      1327 prescriptions regarding infants, 4.3% were mucolytics agents. Main
      indications were rhinopharyngitis, isolated cough, and acute bronchitis. Our
      review did not identify any study of rigorous methodological quality that
      supported the efficacy or safety of mucolytics agents in infants for their in
      label (isolated cough, acute bronchitis) and off-label (rhinopharyngitis)
      indications. Six cases of infants, aged less than eight months, presenting
      paradoxical bronchial congestion during a treatment with mucolytics agents, have
      been reported to the French pharmacovigilance system. No causal relationship was
      established from these cases because of a possible protopathic bias. DISCUSSION:
      Our results concerning mucolytics agents use are similar to those reported by the
      French Health Care Funds. In addition to the lack of studies on efficacy, no
      studies on the dose-response relationship were available, leading to suggested
      dose regimens in the French license of acetylcystein ranging from 44.4 to 16.4 mg
      kg-1 j-1 between one to 24 months. These dose regimens could predispose to
      overdosing in the youngest infants as it seems observed in the six reported
      cases. CONCLUSION: In infants, mucolytics agents efficacy has never been
      demonstrated and some elements suggest poor safety (paradoxical bronchial
      congestion).

PMID- 12503504
TI  - [Acenocoumarol (Sintrom) and fluinidione (Previscan) in pediatrics after cardiac
      surgical procedures].
AB  - PATIENTS AND METHODS: Between 1997 and 2001, 150 children (one month to 16 years
      of age) were treated with oral anticoagulants after cardiac surgery (Fontan's
      operations and congenital heart diseases without valvulopathy: 62%, valvular
      prosthesis: 20%, arrhythmia: 4.6%, thrombosis: 4%, other: 9.4%). They were first
      treated by either unfractionated heparin (49%) or nadroparin (51%), then by
      acenocoumarol (n1 = 114) or fluindione (n2 = 36) until steady state. RESULTS: The
      retrospective analysis of data (age, body weight, international normalized ratio,
      loading and maintenance doses, time to achieve the steady state) led to the
      building of a dosage nomogram usable in pediatrics. CONCLUSION: We demonstrated
      that the mean maintenance dose depended on age and weight. After three years,
      that dose (mg/kg) was getting close to adult values; it was higher before three
      years of age, especially before 12 months (p < 0.01), and very variable from a
      child to another. The recommended loading dose should be as close as possible to
      the effective maintenance dose: within that cohort, about 0.14 and 0.05
      (acenocoumarol) or 1.1 and 0.40 mg kg-1 day-1 (fluindione), before 12 months and
      after three years respectively.

PMID- 12503505
TI  - [Routine use of gene amplification for pertussis diagnosis in children].
AB  - OBJECTIVES: The resurgence of whooping cough observed in France convinced us to
      develop a specific PCR assay to detect B. pertussis in nasopharyngeal secretions
      in parallel of the culture. The aim of our study was to show the value of the PCR
      in routine diagnosis. MATERIAL AND METHODS: From November 1996 to August 2000, in
      two hospitals located in the Yvelines (France), the children consulting for a
      cough compatible with the diagnosis of whooping cough were included in this
      study. A questionnaire including clinical, biological and radiological items was
      completed for each one of these patients. A culture of Bordetella and a detection
      by PCR of B. pertussis were carried out on each nasopharyngeal aspirate. The
      diagnosis of whooping cough was retained if the detection was positive in PCR
      and/or culture. RESULTS: Among the 215 investigated children with suspected cases
      of whooping cough, the diagnosis was positive for 45 (20.9%), of which 39 were
      less than one year old (median: three months). Sixteen (35.5,%) were positive at
      the same time for both the PCR and the culture, 26 (57.8%) for only PCR and three
      (6.7%) for only culture. The PCR was positive in 93.3% of the cases. The results
      were obtained with an average time of 48 hours. The culture was positive in 61.2%
      of the cases with an average time of six days. The monthly distribution of the
      cases of whooping cough was very inhomogeneous and of epidemic appearance. The
      majority of the cases was located between two periods: 42% between November 1996
      and September 1997 and 40% between November 1999 and August 2000. Among the
      infected children, 15 were less than two months old and were not yet vaccinated;
      among the 24 others infants, a delay in the vaccine calendar was noted in 50% of
      the cases. Four children between six and 14 years old were correctly vaccinated.
      The evolution was favourable in all the children. CONCLUSION: The PCR due to its
      sensitivity, its specificity and its rapidity offers to the clinician a powerful
      tool for the diagnosis of whooping cough. Nevertheless, the culture must be
      associated with the PCR, in order to follow the epidemiology and the sensitivity
      to antibiotics of B. pertussis.

PMID- 12503506
TI  - [Herpetic meningitis in the child].
AB  - In children, viral meningitis is usually caused by Enteroviruses. Herpes simplex
      viruses (HSV) are known to be a cause of meningo-encephalitis. HSV-2 has been
      reported to cause recurrent meningitis (Mollaret's meningitis) in adults. CASE
      REPORT: We report the case of a three-year-old girl with HSV-1 meningitis, whose
      evolution with treatment by aciclovir was good. CONCLUSION: HSV-1 has rarely been
      reported as a cause of isolated aseptic meningitis in children. Primary phase of
      herpes simplex virus infection is not usually associated with neurologic
      complications.

PMID- 12503507
TI  - [Tuberculosis in newborns in a tropical neonatology unit].
AB  - We report three cases of tuberculosis observed in a neonatal unit in a country
      characterized with a high endemia of tuberculosis. CASE REPORTS: Case 1. A term
      infant presented at the age of 35 days, with cough since day 18, respiratory
      distress and bronchopneumonia. Her mother had unrecognised tuberculosis since
      pregnancy. Post mortem biopsies of the infant confirmed the diagnosis of
      tuberculosis and social survey found out pulmonary tuberculosis in the newborn's
      aunt. Case 2. A term infant presented at the age of 30 days with cough since day
      13, respiratory distress, nodular pulmonary lesions and right pleural effusion.
      Her mother had cough and stomatitis since the eighth month of pregnancy and
      nodular pulmonary lesions. Tuberculosis and HIV were confirmed in the mother and
      the infant. Social survey found tuberculosis in the newborn's paternal uncle.
      Case 3. A term but hypotrophic infant presented on the first day of life, with
      haemorrhagic troubles and respiratory distress. Tuberculosis and HIV were
      confirmed in the mother and the infant. Social survey found tuberculosis in the
      father, in a friend of her and in her three-month-old child. CONCLUSION:
      Congenital or neonatal tuberculosis is an under-estimated emergent disease, with
      a need for early diagnostic methods and consensual therapeutic protocols to
      improve its management.

PMID- 12503508
TI  - [Neurologic signs revealing a Behcet's disease: two pediatric case reports].
AB  - Behcet's disease can be revealed by neurologic signs. CASE REPORTS: We report two
      pediatric cases of Behcet's disease which initially presented with cerebral
      venous thrombosis. Glucocorticoids, associated with anticoagulant treatment
      allowed a rapid recovery. One of the children presented three years later a
      thrombotic recurrence. CONCLUSION: A cerebral venous thrombosis may reveal
      Behcet's disease.

PMID- 12503509
TI  - [Johanson-Blizzard syndrome: a case report].
AB  - The Johanson-Blizzard syndrome is a rare autosomal recessive syndrome. This
      syndrome includes congenital aplasia of the cutis, aplasia of the alae nasi,
      bilateral hearing loss, dental malformations and pancreatic insufficiency. CASE
      REPORT: We report a sporadic case male infant from nonconsanguineous parents. He
      presented aplasia of the cutis and high anorectal malformation, associated with
      exocrine pancreatic insufficiency. A colostomy was performed at birth and
      anorectal atresia was corrected surgically at two months. Exocrine pancreatic
      insufficiency required immediate enzyme supplementation.

PMID- 12503510
TI  - [Pneumococcal meningitis and resistant bacteria].
AB  - The emergence of resistance has imposed a modification of the protocols for the
      treatment of Streptococcus pneumoniae (S pneumoniae) bacterial meningitis.
      Amoxicillin is no longer adapted. As resistance to C3G appeared, a synergistic
      effect of an association C3G + vancomycine was demonstrated. Thus currently this
      association should be recommended in any case of meningitis supposedly due to S
      pneumoniae. The treatment is then modified according to the evolution and the
      minimal inhibition concentration (MIC) of the bacteria. The strains carrying a
      high level of resistance to cephalosporin (MIC > or = 4 micrograms ml-1) or
      tolerant to vancomycine may cause a therapeutic failure despite an increase of
      the dosage of cephalosporin. Rifampicin, fosfomycine, or imipenem (despite its
      risk of convulsions), may represent alternative options, as long as we do not
      have safe quinolones active on resistant strains of S. pneumoniae. Dexamethasone
      has been formerly implicated in the relapse of pneumococcal meningitis.
      Furthermore, its use is questionable since no evidence of a therapeutic benefit
      has been clearly demonstrated. As a consequence of the resistance phenomenon the
      management of S. pneumoniae meningitis must include particular measures: at least
      resistance to penicillin must be checked by the oxacilline disk and the MIC to
      C3G must be measured by E test; aCSF sample should be obtained between 36 and 48
      hours following the beginning of the treatment to check its sterilization. All
      recent studies have shown a similar prognosis of meningitis due to resistant S.
      pneumoniae as compared to those due to sensitive strains. However, these data
      should be interpreted with caution since in these studies, pneumococcus resistant
      to cephalosporin (the real problem) are not separated from those only resistant
      to penicillin. Furthermore, presently, the incidence of strains highly resistant
      to cephalosporin is still low. The new conjugated vaccine against pneumococcus
      should change the situation if its ability to prevent the circulation of
      resistant strains is confirmed.

PMID- 12503511
TI  - [Treatment of non-painful symptoms in terminally ill children].
AB  - The care of children at the end of life is gradually improving. Nevertheless,
      more than half suffer from intractable symptoms before dying. Although pain has
      been the subject of clinical research, evidence-based data are almost completely
      lacking for other symptoms, highlighting the need for clinical research in
      palliative care. We review the available evidence on fatigue, anorexia, dyspnea,
      respiratory secretions, cough, constipation, mouth dryness, urinary obstruction,
      terminal convulsions and gasping. When evidence is lacking, we offer our empiric
      approach. Short duration benzodiazepines have become an important component of
      treatment that should remain simple, while providing the dying child the comfort
      needed to experience the highest quality relationships with those around him.

PMID- 12503512
TI  - [Radiologic case of the month. Disk calcinosis in the child].

PMID- 12503513
TI  - [Confrontation of children and adolescents with pornography].
AB  - The author describes the influence of pornography on children, focusing on
      pornographical material on the web. Most children escape almost uninjured from
      visualization of pornography. However some are either traumatized, or
      precipitated in a strict perversion. The consequences on adolescents are similar,
      though more complex. The hypersexualization of teenagers may become complicated
      by addiction (so called internet addiction disorder: IAD), isolation, and
      perversion. Recommendations for the parents are presented.

PMID- 12503514
TI  - [The development of visual function].
AB  - Development of vision mainly takes place during the first year of life. Visual
      function cannot be restricted to the measurement of visual acuity. Indeed it is a
      plural function including functions of environment exploration, relative
      appreciation of objects, control of body position and movements organization,
      acquisition of knowledge and communication. From an analytical point of view
      visual function comprises sensorial (such as visual acuity), cognitive (cerebral
      processing of sensorial information) and oculomotor elements. Synthetically it
      may be seen as a neuro-visual loop organized around the eye, by turns sensor
      (vision) and effector (look). This neurovisual loop representation is of interest
      as it allows better recognition and analysis of the neurovisual pathologies
      encountered in children with cerebral injuries, especially former premature
      infants.

PMID- 12503515
TI  - [Management of children with sickle cell anemia: a collaborative work].
AB  - Treatment of children with sickle cell disease has been impressively improved
      during recent years. Neonatal screening is now generalized to all continental
      France. Coupled with parents' education and a comprehensive care program, it
      allows a reduction of pneumococcal infections, and of the mortality related to
      splenic sequenstration, the occurrence of cerebrovascular accidents being also
      reduced by the use of transcranial Doppler ultrasonography. However, to be
      effective these measures require a close collaboration not only between parents
      and the medical team but frequently also between the medical team and social
      workers, as many affected children living in France are born from first
      generation African migrants, for whom it may be difficult to understand and/or to
      apply the care program.

PMID- 12503516
TI  - [Respiratory syncytial virus pneumonia revealing and acute lymphoblastic leukemia
      with mediastinal compression].

PMID- 12503517
TI  - [Trisomy 13 and neonatal hyperinsulinism].

PMID- 12503518
TI  - [Fluoride supplementation must be initiated at birth in children in France].

PMID- 12503519
TI  - [Anomalies of dental development in children receiving chemotherapy].

PMID- 12503520
TI  - [Tolerance of nitrous oxide-oxygen sedation for painful procedures in emergency
      pediatrics: report of 600 cases].

PMID- 12503521
TI  - Effect of osmotic pressure in the solvent extraction phase on BSA release profile
      from PLGA microspheres.
AB  - This study investigated the influence of osmotic pressure in the organic solvent
      extraction phase on release profile of bovine serum albumin (BSA) from
      poly(lactide-co-glycolide) (PLGA) microspheres. BSA-loaded PLGA microspheres with
      a target load of 10% were prepared by a double emulsion phase separation method.
      All the microsphere batches were fabricated in the same conditions except that in
      the organic solvent (CH2Cl2) evaporation step. Different concentrations of NaCl
      (0, 1.8, and 3.6%) or sucrose (20%) were used to generate a range of osmotic
      pressures in the extraction aqueous phase. These microspheres were characterized
      for incorporation efficiency, surface and internal morphology, particle size,
      protein stability, and in vitro release. The microspheres were spherical with
      particle size ranging from 16.8 to 27.8 microns. Higher osmotic pressure resulted
      in a denser internal structure although similar nonporous surface morphology was
      observed with all batches. No significant difference in encapsulation efficiency
      existed from batch to batch (87-94%). Sodium dodecyl sulfate-polyamide gel
      electrophoresis showed that BSA integrity was well retained. The release profile
      of the batch prepared with only water as the continuous (solvent extraction)
      phase exhibited a 79% burst release in the first 24 hr followed by a plateau and
      then a little release after 21 days. In the presence of NaCl or sucrose, the
      burst effect significantly decreased with increase in osmotic pressure in the
      extraction aqueous phase, which was then followed by sustained release for 35
      days. A mass balance was made when the release terminated. Therefore, in the
      organic solvent extraction and evaporation step, increasing the osmotic pressure
      in the aqueous phase both reduced the burst release from the microspheres and
      improved the subsequent sustained release profile.

PMID- 12503522
TI  - Effect of thermal treatment during the preparation of aluminum hydroxide adjuvant
      on the protein adsorption capacity during aging.
AB  - Six aluminum hydroxide adjuvants, poorly crystalline aluminum oxyhydroxide
      (AlOOH) were prepared using different thermal treatments of amorphous aluminum
      hydroxide (Al(OH)3) in an effort to increase the protein adsorption capacity. All
      of the adjuvants initially exhibited a higher protein adsorption capacity.
      However, the protein adsorption capacity decreased during aging at room
      temperature. X-ray and differential centrifugal sedimentation analysis revealed
      that complete dehydration of amorphous aluminum hydroxide to aluminum
      oxyhydroxide is required to produce a stable adjuvant. Any residual amorphous
      aluminum hydroxide will spontaneously transform to crystalline aluminum hydroxide
      during aging at room temperature. Since crystalline aluminum hydroxide has a
      small surface area, the protein adsorption capacity of adjuvants containing
      amorphous aluminum hydroxide decreased by 30-40% when stored for 6 months at room
      temperature.

PMID- 12503523
TI  - Influence of plasticizer type and coat level on Surelease film properties.
AB  - Two commercially available formulations of aqueous ethylcellulose dispersion
      differing in their plasticizer, i.e., Surelease/E-7-7050 containing dibutyl
      sebacate (DBS) and Surelease/E-7-7060 containing glyceryl tricaprylate/caprate
      (GTC), were evaluated and compared for their film properties as a function of
      polymeric coat level. Ibuprofen tablets were coated at 1, 2, 3, and 5% w/w levels
      using each Surelease formulation, and the coated tablets were evaluated for their
      drug release characteristics, coat reflectivity (gloss), surface texture, Brinell
      hardness, and elastic modulus. The drug release was dependent on the coat level
      and followed Hixson-Crowell cube-root model at 1% coat level. However, at > or =
      2% coat levels, the release from tablets coated with GTC plasticized formulation
      appeared to be best described by non-Fickian release mechanism and that from
      tablets coated with DBS plasticized formulation appeared to follow apparent zero
      order release mechanism. At equal coat levels, tablets coated with GTC
      plasticized Surelease yielded lower drug release rates, higher reflectivity
      (gloss), lower surface roughness, higher Brinell hardness, and lower elastic
      modulus than those coated with DBS plasticized formulation. A good correlation
      was observed between the drug release rates and the reflectivity and surface
      texture of the coated tablets. The film-coats of GTC plasticized formulation were
      harder and more elastic than those of DBS plasticized formulation indicating
      better mechanical integrity.

PMID- 12503524
TI  - Influence of type and level of water-soluble additives on drug release and
      surface and mechanical properties of Surelease films.
AB  - Ethylcellulose in combination with water-soluble additives has been used in the
      development of microporous membrane-coated dosage forms. In the present study,
      application of three types of water-soluble additives, namely polyethylene
      glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in
      the order of lower to higher average polymer size and molecular weight; dextrose
      equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity
      modifiers in the films of a commercially available aqueous ethylcellulose
      dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate)
      was investigated. The effect of type and level of these additives on drug release
      characteristics and surface and mechanical properties of the polymeric films was
      studied. Each additive was incorporated at 20 and 30% levels in the polymeric
      dispersion based on its solids content. Ibuprofen tablets were coated using the
      polymeric dispersion with and without additive at 3% w/w coat level in a fluid
      bed equipment. The coated tablets were evaluated for their drug release rate,
      coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential
      scanning calorimetric analysis of the films was performed to determine the
      physico-chemical changes in the applied film-coats. The rate of drug release,
      hence film porosity, was observed to be dependent on the type and level of the
      additive added. The molecular weight of the additive and its concentration in the
      polymeric dispersion had significant influence on the rate of drug release,
      hardness, and elasticity of the film-coats.

PMID- 12503525
TI  - Roller compaction and tabletting of St. John's wort plant dry extract using a gap
      width and force controlled roller compactor. I. Granulation and tabletting of
      eight different extract batches.
AB  - The purpose of this study was to investigate the influence of roller compaction
      parameters on granule and tablet quality of a dry herbal extract from St. John's
      wort (Hypericum perforatum L.), which is widely used in the treatment of mild to
      moderate depressive disorders. Eight different extract batches were blended with
      0.5, 2, and 5% of magnesium stearate and were compacted at different compaction
      forces using a gap width and force controlled roller compactor. The ribbon formed
      was milled into granules having mean particle sizes up to 700 microns. The roller
      compaction of the extracts decreased significantly the angle of repose from about
      45 to 32 degrees and the Hausner ratio from about 1.2 to 1.1. Tabletting of
      granulated extract instead of extract powder effectively reduced not only dust
      and feeding problems during the tabletting process but also prevented capping.
      The incorporation of 2 and 5% of magnesium stearate into the roller compacted
      extract reduced significantly the sticking of the dry herbal extracts to the
      punch faces without affecting the crushing strength of the tablets. Tablets
      containing granulated extracts exhibited a 3-fold lower disintegration time of
      about 12 min compared to tablets containing extract powder. Dissolution studies
      revealed that hyperforin, hypericin, and rutin were more rapidly released from
      tablets containing granulated extract. Therefore, roller compaction leveled out
      the differences in technological properties between the eight dry herbal extracts
      and compression of granulated extract significantly improved tablet quality.

PMID- 12503526
TI  - Roller compaction and tabletting of St. John's wort plant dry extract using a gap
      width and force controlled roller compactor. II. Study of roller compaction
      variables on granule and tablet properties by a 3(3) factorial design.
AB  - The purpose of this study was to investigate the influence of roller compaction
      parameters and the amount of magnesium stearate used in dry granulation on
      granule and tablet properties of a dry herbal extract from St. John's wort
      (Hypericum perforatum L.). Two different extract batches were blended with
      magnesium stearate and compacted using a gap width and force controlled roller
      compactor. A 3(3) factorial design was used to evaluate the influence of the
      three independent variables, the amount of magnesium stearate, the roller
      compaction force, and the granulating sieve size on the mean particle size of
      granulated extracts and on the disintegration time of tablets containing these
      granulated extracts. The evaluation was done by multilinear stepwise regression
      analysis. The mean particle size d50 (R2 > 0.9) of both compacted extracts
      increased with increasing compaction force and with granulating sieve size. The
      disintegration time of the tablets was mostly in the range 5-15 min and increased
      slightly with increasing magnesium stearate concentration in the compacted
      extract and with decreasing compaction force of the roller compaction. The
      incorporation of magnesium stearate into the granulated extract reduced its
      potential negative influence on the disintegration time, while maintaining its
      functionality as a lubricant.

PMID- 12503527
TI  - Preformulation studies and characterization of proposed chondroprotective agents:
      glucosamine HCl and chondroitin sulfate.
AB  - PURPOSE: Glucosamine HCl and chondroitin sulfate are proposed chondroprotective
      agents commonly used as dietary supplements. This study examined the
      physicochemical and mechanical properties of chondroitin sulfate, glucosamine HCl
      powder, and glucosamine HCl granulation obtained from various sources. METHODS:
      The particle size distributions of the materials were determined using sieve
      analysis and time-of-flight techniques. Polarized light microscopy was used to
      examine particle morphology. Powder x-ray diffraction studies, moisture sorption
      isotherms, deformation behavior, powder flow, and compaction characteristics were
      also investigated. The polarized light microscopy and x-ray diffraction patterns
      showed that chondroitin sulfate is amorphous while glucosamine HCl is
      crystalline. Particle sizes of chondroitin sulfate and glucosamine HCl varied
      widely, depending on their source or manufacturing technique (e.g., granulation).
      The studied samples of shark-derived chondroitin sulfate had a small median
      particle size (4 microns) compared to that derived from bovine cartilage (17
      microns). Different moisture sorption profiles were obtained for the glucosamine
      HCl granulations studied. Glucosamine HCl granulation from Supplier I showed no
      observable moisture sorption, while the granulation from Supplier II showed an
      approximately 5% weight gain. Conversely, chondroitin sulfate was extremely
      hygroscopic and deliquescent. The Carr's indices for glucosamine HCl samples
      ranged from 12.5 to 31.5; for chondroitin sulfate the values were 25.2 and 53.6.
      The compression analysis showed that all chondroitin sulfate samples exhibited
      plastic deformation behavior, with the shark-derived chondroitin sulfate forming
      superior compacts when compared to the bovine. The dominant mechanism of
      compression of glucosamine HCl powder was brittle fracture, whereas wet
      granulated glucosamine HCl exhibited plastic deformation with enhanced mechanical
      strength. CONCLUSIONS: The physicochemical and mechanical characteristics between
      the various dietary supplements studied varied greatly. Data obtained from this
      study provide an understanding of the physicomechanical behavior of chondroitin
      sulfate and glucosamine HCl. Application of this knowledge would facilitate
      development of stable solid dosage forms containing these materials.

PMID- 12503528
TI  - Development of a lag time coating for drug-layered fish feed pellets.
AB  - The purpose of this work was to develop a release-delaying coat for drug-layered
      fish pellets, in order to prevent a premature release of the drug in the tank
      water but allowing a rapid release after uptake by the fish. Blank pellets were
      prepared in a rotary processor and drug layered in a Wurster coater with bovine
      serum albumin or riboflavin using hydroxypropyl methyl cellulose (HPMC) as a
      binder. On the drug-loaded pellets, different mixtures of ethyl cellulose (EC)
      and HPMC were applied as the release-delaying coat. The aim was to obtain less
      than 10% drug release during the first 10 min followed by a fast release after
      the "lag" period, resulting in a sigmoidal release profile. In order to prevent
      coat bursts it was necessary to increase the amount of plasticizer from 20 to 40%
      triethylcitrate. To have a complete coat around the pellets, the thickness of the
      coat (amount EC) was important up to a certain level. The EC/HPMC ratio had a
      decisive influence on optimizing the permeability of the coating and realizing a
      sigmoidal release profile. The release rate was studied as a function of several
      formulation variables and physicochemical parameters (salinity, pH, and
      temperature) of the dissolution medium as the coating system is intended for
      different fish species. Salinity of the water proved to be important as well as
      the temperature. The developed system seems to be promising for a lot of
      ichthyologic applications, although it has to be evaluated for each intended
      drug, keeping in mind the properties of the particles to be coated, the fish
      species, and the environment.

PMID- 12503529
TI  - Influence of thermal processing on the properties of chlorpheniramine maleate
      tablets containing an acrylic polymer.
AB  - The purpose of this investigation was to determine the effects of thermal
      processing and post-processing thermal treatment on the release properties of
      chlorpheniramine maleate (CPM) from matrix tablets containing Eudragit RS PO and
      triethyl citrate (TEC). CPM tablets containing Eudragit RS PO with and without
      TEC were prepared by direct compression (DC), high shear hot-melt granulation
      (HMG), and hot-melt extrusion (HME). X-ray diffraction patterns showed that the
      CPM was distributed in Eudragit RS PO at the molecular level following HME. The
      thermogravimetry analysis (TGA) profiles of CPM, Eudragit RS PO, and TEC
      demonstrated that these materials were thermally stable during both the high
      shear HMG and HME processes. The tablets were subjected to post-processing
      thermal treatment by storing the tablets at 60 degrees C in open containers for
      24 hr. Tablets prepared by DC showed the highest drug release rate constant of
      36.2% hr-1/2. When 4% TEC was incorporated into the formulation, the drug release
      rate constant for the directly compressed tablets decreased to 32.4% hr-1/2.
      After high shear HMG and HME of the powder blend containing 4% TEC, the drug
      release rate constant decreased to 30.8 and 13.8% hr-1/2 for the respective
      processes. The drug release rate constants for all tablets decreased following
      post-processing thermal treatment. The reduction in release rate was due to an
      increase in the intermolecular binding and entanglement between drug molecules
      and polymer molecules that occurred during thermal processing. Post-processing
      thermal treatment of the hot-melt extrudates had a minimal effect on the drug
      release rate since the HME process enhanced the drug and polymer entanglement to
      a greater extent.

PMID- 12503530
TI  - Solid-state characterization of fluconazole.
AB  - Two polymorphs and three solvates of fluconazole were isolated and characterized
      by x-ray powder diffractometry, IR spectroscopy, differential scanning
      calorimetry (DSC), thermogravimetry, and their dissolution rates. The different
      forms were prepared by crystallization of the original powder in different
      solvents at different cooling rates. X-ray diffraction patterns of the five solid
      modifications exhibited substantial differences in both the intensity and
      position of the peaks. FTIR spectra of the five different solid-state
      modifications also exhibited differences in the peaks' positions and intensities.
      DSC thermogram of anhydrate form I showed a single melting point at 139.2 degrees
      C. Anhydrate form II showed two endothermic peaks at 136.5 and 139.2 degrees C
      and one exothermic peak in between. The DSC thermogram of acetone 1/4 solvate
      exhibited two endothermic peaks at 75.5 and 139.2 degrees C. Benzene 1/7 solvate
      exhibited two endothermic peaks at 131.5 and 138.8 degrees C. Hydrate E exhibited
      two endothermic peaks at 102.7 and 139.2 degrees C. The DSC thermogram of
      anhydrate form II showed that this form is sensitive to the application of a
      mechanical force. The solubility study showed that anhydrate form II and acetone
      1/4 solvate have higher solubilities than anhydrate form I while benzene 1/7
      solvate and monohydrate have lower solubilities than anhydrate form I. The
      intrinsic dissolution study confirmed these results.

PMID- 12503531
TI  - Special section from the workshop "Ecosynthesis: creating open and closed
      ecosystems on Mars".

PMID- 12503532
TI  - [At threshold of the jubilee].

PMID- 12503533
TI  - [The Moscow military hospital during the Fatherland War of 1812. (On the 190th
      anniversary of the Battle of Borodino)].

PMID- 12503534
TI  - [Contribution of Russian military doctors to 19th century Moscow public health].

PMID- 12503535
TI  - [Results of GISSI Prevenzione: diet, drugs, and cardiovascular risk. Researchers
      of GISSI Prevenzione].

PMID- 12503536
TI  - [Prevention in coronary postangioplasty restenosis with omega-3 fatty acids.
      Results of the Italian study on prevention of restenosis with esapent (ESPRIT)].

PMID- 12503538
TI  - [Surgery of the spleen in antiquity].
AB  - Splenic surgery, a common practice in Antiquity? Such a question will appear
      somewhat provocative despite an ample mention of such facts in Roman and Greek
      classic literature. This paper intends to explore the large border standing
      between myths where the spleen keeps a major place and reality which is, on this
      subject, far from easy to decipher. In final analysis, it seems likely that there
      had always existed, from the very early ages, some form of splenic cauterisation.
      The type of procedures reported in the texts cannot be interpreted as variant of
      the ritual scarifications widely practised until recently in many countries. On
      the other hand, the idea that physicians, at the time of Antiquity, could perform
      splenectomy does not seem, in spite of Ancient authors assumptions, to be
      considered. In fact, there is no direct testimony available on this subject in
      Latin or Greek medical literature. We suggest that the so-called "splenectomies"
      of Antiquity could have been surgical "make-believes" closely similar to the
      quack practices which can be yet observed in some remote countries.

PMID- 12503539
TI  - [Gilbert Ballet's discourse on the method: rules in psychiatry].
AB  - G. Ballet, former Chairman (1909-1910) of the S.F.H.M., wrote a remarkable
      "Discourse on the Method" for Psychiatry in order to introduce his "Clinics"
      (1887). This work, revisited for our present purpose, forecasts the main theories
      in search of a scientific psychiatry. It gets thereafter, a premonitory value.

PMID- 12503540
TI  - Nurses as partners.

PMID- 12503541
TI  - Telecommuting and privacy.

PMID- 12503542
TI  - [Corvisart's aphorisms in cardiology as recorded by Laennec].
AB  - The aphorisms which Laennec recorded at the "Hopital de la Charite" in 1802
      ("Anno X") during the lectures given by his master Jean-Nicolas Corvisart were,
      to a large extent, devoted to cardiology. They illustrate Corvisart's teaching
      methods and, above all else, they allow to discern his medical conceptions, based
      on acuteness of semiotic study, on rigour of physical examination, on analysis of
      signs and their confrontation with anatomical data, thereby opening the era of
      anatomico-clinical approach and of a novel medicine, which his disciple Laennec
      was to purse and amplify. Also, they witness to Corvisart's clinical sense and
      premonition of diseases, including heart diseases, which were to be identified
      much later on.

PMID- 12503543
TI  - Management of acute coronary syndromes in patients presenting without persistent
      ST-segment elevation.

PMID- 12503544
TI  - [Bellini's death in 1835 and his biography].
AB  - Bellini died all of a sudden in 1835 whereas he was young and in good health. An
      amoebic intestinal disease and a liver abscess have been proved by the post
      mortem examination. In fact the artist was living alone in a remote house outside
      Paris in Puteaux. His death was very painful as he did not receive any correct
      treatment which might have saved his life. Thus the circumstances of his death
      remain a puzzle for the historians.

PMID- 12503545
TI  - [O-Ine, the first trained woman physician in Japan].

PMID- 12503547
TI  - Importance of traceable pH measurements.

PMID- 12503546
TI  - [The book of the physician].

PMID- 12503548
TI  - [The place for curing the sick].

PMID- 12503549
TI  - Multiple myeloma incidence in the world.

PMID- 12503550
TI  - [The terror of the plague of 1347].

PMID- 12503553
TI  - [Historic hospitals in Europe].

PMID- 12503555
TI  - [The fifth division of the hospital of Bicetre in 1830].

PMID- 12503556
TI  - Nobel prizes for cell death research.

PMID- 12503557
TI  - An interview with Dr. Agnes Glaus.

PMID- 12503558
TI  - [The female pioneers of health].

PMID- 12503559
TI  - [The hospital for convicts at Marseille].

PMID- 12503560
TI  - The centaur: veterinary symbol and logo of the American Veterinary Medical
      History Society.

PMID- 12503561
TI  - Protection of animals through modern legislation.

PMID- 12503562
TI  - Notes on Bell-Sejnowski PDF-matching neuron.
AB  - This article investigated the behavior of a single-input, single-unit neuron
      model of the Bell-Sejnowski class, which learn through the maximum-entropy
      principle, in order to understand its probability density function and matching
      ability.

PMID- 12503563
TI  - Animal therapy over the ages: 8. self-treatment.

PMID- 12503564
TI  - One hundred years of colic: the diagnosis and treatment of equine
      gastrointestinal disease in the twentieth century.

PMID- 12503565
TI  - This view of science: Stephen Jay Gould as historian of science and scientific
      historian, popular scientist and scientific popularizer.
AB  - Science historian Ronald Numbers once remarked that the two most influential
      historians of science of the 20th century were Thomas Kuhn and Stephen Jay Gould.
      All historians are deeply familiar with Kuhn's work and influence, and most know
      of the remarkable impact Gould has had on evolutionary theory through both his
      professional and popular works. But little attention has been paid to the depth,
      scope, and importance of Gould's role as historian and philosopher of science,
      and his use of popular science exposition to reinforce old knowledge and generate
      new. This paper presents the results of an extensive quantitative content
      analysis of Gould's 22 books, 101 book reviews, 479 scientific papers, and 300
      Natural History essays, in terms of their subject matter (Evolutionary Theory,
      History and Philosophy of Science, Natural History, Paleontology/Geology, Social
      Science/Commentary), and thematic dichotomies (Theory-Data, Time's Arrow-Time's
      Cycle, Adaptationism- Nonadaptationalism, Punctuationism-Gradualism, Contingency
      Necessity). Special emphasis is placed on the interaction between the subjects
      and themata, how Gould has used the history of science to reinforce his
      evolutionary theory (and vice versa), and how his philosophy of science has
      influenced both his evolutionary theory and his historiography. That philosophy
      can best be summed up in a quotation from Charles Darwin, frequently cited by
      Gould: 'All observation must be for or against some view if it is to be of any
      service'. Gould followed Darwin's advice throughout his career, including his
      extensive writings on the history and philosophy of science.

PMID- 12503566
TI  - Longer nuclear medicine residency requirements proposed.

PMID- 12503567
TI  - One additional year of training in nuclear medicine: will it help or hurt?

PMID- 12503568
TI  - Nuclear medicine: for all the world.

PMID- 12503569
TI  - 2003 HOPPS final rule published. Hospital Outpatient Prospective Payment System.

PMID- 12503570
TI  - SNM publishes Specific Guidance on NRC Part 35.

PMID- 12503571
TI  - The cases of John Bunyan, Part 1.: Taine and Royce.
AB  - John Bunyan was a seventeenth-century religious reformer who is nowadays widely
      known for his Pilgrim's Progress and also for his spiritual autobiography Grace
      Abounding to the Chief of Sinners. In the nineteenth century he was diagnosed, on
      the basis of his revelations in that autobiography, as suffering from a variety
      of mental pathologies. In this study we track his 'psychiatric career' through
      the work of H. Taine and J. Royce (Part 1), and W. James and P. Janet (Part 2).
      The examination of these authors' practices of 'retrospective psychiatry' allows
      us to bring to light some changes in psychiatric concepts in the late nineteenth
      century, and to investigate both the use of cases in psychological reasoning, and
      translations from religious to psychiatric idioms.

PMID- 12503572
TI  - Two hundred years of psychiatry at Leipzig University: an overview.
AB  - The University of Leipzig boasts a long tradition in the field of psychiatry. In
      1811 J.C.A. Heinroth was appointed as the first professor of psychiatry in
      Europe. In 1877 brain researcher P. Flechsig inherited his chair, but did not
      significantly contribute to the progress of this speciality. His first assistant
      was E. Kraepelin. Flechsig's successors, O. Bumke and P. Schroder, included
      psychological as well as sociogenetic topics in their research. The latter did
      pioneering work for the institutionalization of child and adolescent psychiatry.
      After the destruction of the hospital in 1943, R. A. Pfeifer re-organized its
      operation, and he also made remarkable contributions to the study of the
      angiostructure of the brain. With D. Muller-Hegemann, who had a major influence
      on German psychotherapy, the social psychiatric era began, and it was
      successfully continued under B. Schwarz, K. Weise and the hospital's present
      head, M. C. Angermeyer. Under Angermeyer the institutional basis of the clinic
      has been improved to include, among its other services, a day clinic and an
      optionally open-closed ward.

PMID- 12503573
TI  - The British reaction to dementia praecox 1893-1913. Part 1.
AB  - Emil Kraepelin introduced the concept of dementia praecox in 1893. The eventual
      acceptance of the concept brought a degree of clarity and order previously
      unknown to psychiatric nosology. The pre-Kraepelin era had been dominated by
      concepts such as mania, melancholia and adolescent insanity. After Kraepelin
      these ideas were abandoned in favour of the two great concepts of dementia
      praecox and manic depressive insanity, both of which remain active within modern
      psychiatry in the form of schizophrenia and bipolar disorder. This two-part study
      focuses on the early British reaction to Kraepelin's concept, from 1893, when he
      first introduced it, to 1913 when it gained general recognition. It examines the
      struggle experienced by the proponents of dementia praecox before the concept's
      acceptance by most British psychiatrists in 1913. It argues that both
      clinical/professional and linguistic factors influenced the British response to
      dementia praecox. Part 1 of this study describes the backdrop to the development
      of Kraepelin's ideas and examines the response to the concept in the British
      psychiatric textbooks and journals of the period. Part 2 will explore reaction to
      the concept in the professional meetings of the period, and will also examine and
      evaluate the key issues arising from the debate.

PMID- 12503574
TI  - Lumping or splitting the childhood leukodystrophies.

PMID- 12503575
TI  - Hysteria and hypnosis as ongoing processes of negotiation. Ilma's case from the
      Austro-Hungarian Monarchy. Part 2.

PMID- 12503576
TI  - Out of sight.

PMID- 12503577
TI  - About the limits of psychiatric knowledge. Classic Text No. 51.

PMID- 12503578
TI  - Klaus Conrad (1905-1961).
AB  - Klaus Conrad (1905-1961) was an internationally known figure in the field of
      neuropsychology and psychopathology. He applied Gestalt psychology to give a
      better understanding of the aphasias, the symptomatic psychoses and incipient
      schizophrenia.

PMID- 12503579
TI  - The future's in the stars. Interview by Alastair McLellan.

PMID- 12503580
TI  - Essay review. [Review of: Andrews, J and Scull, A. Undertaker of the mind: John
      Monro and mad-doctoring in Eighteenth-century England. London, Berkeley and Los
      Angeles: University of California Press, 2001].

PMID- 12503581
TI  - Thymoma in patients with MG: characteristics and long-term outcome.
AB  - OBJECTIVE: To examine the characteristics of thymoma when associated with MG and
      to evaluate those conditions that can complicate management and affect survival.
      METHODS: The study includes 207 myasthenic patients who were operated on for
      thymoma, with at least 1-year follow-up from surgery. MG severity and response to
      treatment, the occurrence of paraneoplastic diseases and extrathymic
      malignancies, thymoma histologic types and stages, adjuvant therapy, tumor
      recurrences, and causes of death were recorded. RESULTS: MG-associated thymoma
      was predominantly of B type and was invasive in the majority of patients. MG was
      generally severe, and most patients remained dependent on immunosuppressive
      therapy. Other paraneoplastic disorders and extrathymic malignancies were found
      in 9.66 and 11.11% of patients. Thymoma recurrences occurred in 18 of 115
      patients with invasive tumors (15.65%) and were often associated with the
      onset/aggravation of autoimmune diseases. On completion of the study, MG and
      thymoma accounted for a similar mortality rate. CONCLUSIONS: Thymoma should be
      considered as a potentially malignant tumor requiring prolonged follow-up. The
      presence of myasthenic weakness can still complicate its management. Thymoma
      related deaths are bound to outnumber those due to MG in the future.

PMID- 12503582
TI  - Transcranial magnetic stimulation techniques in clinical investigation.
AB  - Transcranial magnetic stimulation (TMS) is a technique that can activate cortical
      motor areas and the corticospinal tract without causing the subject discomfort.
      Since TMS was introduced, numerous applications of the technique have been
      developed for the evaluation of neurologic diseases. Standard TMS applications
      (central motor conduction time, threshold and amplitude of motor evoked
      potentials) allow the evaluation of motor conduction in the CNS. Conduction
      studies provide specific information in neurologic conditions characterized by
      clinical and subclinical upper motor neuron involvement. In addition, they have
      proved useful in monitoring motor abnormalities and the recovery of motor
      function. TMS also gives information on the pathophysiology of the processes
      underlying the various clinical conditions. More complex TMS applications (paired
      pulse stimulation, silent period, ipsilateral silent period, input-output curve,
      and evaluation of central fatigue) allow investigation into the mechanisms of
      diseases causing changes in the excitability of cortical motor areas. These
      techniques are also useful in monitoring the effects of neurotrophic drugs on
      cortical activity. TMS applications have an important place among the
      investigative tools to study patients with motor disorders.

PMID- 12503583
TI  - Ulerythema ophryogenes and keratosis pilaris.

PMID- 12503584
TI  - Pathologic quiz case: a 34-year-old man wiht a right middle finger mass.
      Mycobacterial soft tissue spindle cell tumor in acquired immunodeficiency
      syndrome.

PMID- 12503585
TI  - Pathologic quiz case: chronic anemia with red cell aplasia and lymphocytosis in a
      middle-aged man. T-cell large granular lymphocyte leukemia.

PMID- 12503586
TI  - Pathologic quiz case: an 86-year-old woman with draining sinuses of the tibia.
      Echinococcosis (hydatid cyst) of the bone.

PMID- 12503587
TI  - Pathologic quiz case: an incidental gastric massin a 71-year old man who
      presented with pancreatic pseudocyst. Gastric glomus tumor.

PMID- 12503588
TI  - Pathologic quiz case: left eye proptosis, ptosis, and blindness.
      Hemangiopericytoma of the orbit.

PMID- 12503589
TI  - Palcenta accreta.

PMID- 12503590
TI  - Cardiac rhabdomyoma.

PMID- 12503591
TI  - The role of HLA antigens in chronic hepatitis B virus infection.
AB  - OBJECTIVE: To investigate the mechanism underlying the development of chronic
      hepatitis B virus infection (HBV) in Turkish population using HLA tissue typing.
      METHODS: The study group I consisted of 20 patients with HBV-related chronic
      liver disease (cirrhosis, chronic active hepatitis or chronic persistent
      hepatitis). The study group II included 30 HBV chronic carriers. The control
      group consisted of 50 healthy subjects with negative serologic markers for HBV.
      HLA typing was performed by Terasaki's microlymphocytotoxicity method. RESULTS:
      The frequencies of HLA-DR13 and DQ3 were significantly higher in the patients
      with HBV-related chronic liver disease compared to those of control group. The
      absence of HLA-A24 and CW1 was also significant in group I. The frequencies of
      HLA A2, B8, B13, CW3, DR13 were significantly higher in group II compared to the
      control group. There were increased frequencies of HLA- B8, B13, DR7, DR13, and
      DQ3 in both group I and group II. CONCLUSION: HLA-A24 AND Cw1 were associated
      with low risk for HBV-related chronic liver disease and HLA- B13, B8, DR7, DR13
      and DQ3 were associated with high risk for chronic HBV infection in the Turkish
      population (JPMA 52:253;2002).

PMID- 12503592
TI  - Select committee's concerns about delays on bovine TB.

PMID- 12503593
TI  - Pestiviral infections in sheep and pigs in Northern Ireland.
AB  - Serological surveys were carried out to determine the prevalence of pestiviral
      infections in sheep and pigs in Northern Ireland. Sera from 918 ewes in 92 flocks
      from 10 regions were tested by ELISA for antibodies to border disease virus and
      positive results were obtained from 49 ewes (5.3 per cent) in 28 flocks (30.4 per
      cent). There were highly significant geographical variations in its flock
      prevalence ranging from 0 per cent in the Enniskillen region to 70 per cent in
      the Coleraine region. There was no significant association between the proportion
      of seropositive flocks and the presence of cattle on the farm (P = 0.583). In the
      positive flocks, the average rate of seroprevalence was 17.5 per cent, and the
      highest was 40 per cent. Comparative neutralisation studies on 14 positive sera
      with bovine viral diarrhoea virus type I (BVDV I) and border disease virus
      revealed higher titres (> or = four-fold) to BVDV I in all cases. Only one
      positive result was obtained when fluids from 186 aborted ovine fetuses were
      tested for border disease virus by ELISA. Serum samples from 680 pigs in 46 herds
      were tested for virus neutralising antibodies to border disease virus. Twenty
      sera (2.9 per cent) were cytotoxic, and only one of the remaining 660 sera gave a
      positive result. This sample tested negative for classical swine fever by ELISA,
      and comparative neutralisation studies showed that it had a four-fold higher
      titre to BVDV I than to border disease virus.

PMID- 12503594
TI  - Detection of Mycoplasma synoviae in clinically normal pheasants.
AB  - Mycoplasma synoviae was isolated from the tracheas of seven clinically normal
      pheasants found in the vicinity of a chicken farm infected with M synoviae, but
      not from 120 pheasants and partridges with respiratory disease. When specimens
      were examined by the polymerase chain reaction only two additional pheasants
      infected with M synoviae were identified, one healthy and one diseased.

PMID- 12503595
TI  - Surfactant proteins in bronchoalveolar lavage fluid of horses: assay technique
      and changes following road transport.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for equine surfactant
      proteins SP-A and SP-D in bronchoalveolar lavage fluid (BALF). Anti-equine SP-A
      or SP-D monoclonal antibodies (mAb) were produced by hybridoma technology,
      purified by the antibody purification reagent, and analysed by Western blotting
      analysis. The immunoreaction (two-site sandwich ELISA) with a mAb, peroxidase
      labelled mAb and BALF sample was carried out simultaneously and analytical
      recovery and precision were assayed. Six mAb for SP-A and four mAb for SP-D were
      successfully cloned in limiting dilution to monoclonality. These mAb were reacted
      with equine SP-A or SP-D on Western blotting analysis. For SP-A, a combination of
      solid-phase TA08 and horseradish peroxidase (HRP)-conjugated WA28 was found to be
      more sensitive than other combinations, gave a good dose response and was capable
      of measuring 0.78 to 100 ng of protein/ml. For SP-D, a combination of solid-phase
      TD13 and HRP-conjugated WD19 was found to be more sensitive than other
      combinations, had a good dose response and was capable of measuring 0.78 to 200
      ng of protein/ml. The assay was used to determine the effect of 41 hours of road
      transport on the concentrations of SP-A and SP-D in the BALF of 30 horses. The
      concentrations of SP-A and SP-D decreased by 55 per cent and 36 per cent,
      respectively, decreases similar to the decrease in phosphatidylglycerol
      concentration previously reported by the authors.

PMID- 12503596
TI  - Canine von Willebrand's disease type 2 in German wirehair pointers in the
      Netherlands.

PMID- 12503597
TI  - Influence of milk from cows persistently infected with BVD virus on bulk milk
      antibody levels.

PMID- 12503598
TI  - Gastrointestinal parasites in ostriches (Struthio camelus).

PMID- 12503599
TI  - Susceptibility of cattle to Ehrlichia risticii, the causative agent of Potomac
      horse fever.

PMID- 12503600
TI  - Epidemiology of the 2000 CSF outbreak in East Anglia: preliminary findings.

PMID- 12503601
TI  - Bulk tank milk failures.

PMID- 12503602
TI  - Consequences of ivermectin-resistant nematodes in sheep.

PMID- 12503603
TI  - Assisted reproduction in the dog.

PMID- 12503604
TI  - Lunar influence?

PMID- 12503605
TI  - The alpha1b-adrenergic receptor subtype: molecular properties and physiological
      implications.
AB  - The aim of this review is to summarize some of the main findings from our
      laboratory as well as from others concerning the biochemical, molecular, and
      functional properties of the alpha1b-adrenergic receptor. Experimental and
      computational mutagenesis of the alpha1b-adrenergic receptor have been
      instrumental in elucidating some of the molecular mechanisms underlying receptor
      activation and receptor coupling to Gq. The knockout mouse model lacking the
      alpha1b-adrenergic receptor has highlighted the potential implication of this
      receptor subtype in variety of functions including the regulation of blood
      pressure, glucose homeostasis, and the rewarding response to drugs of abuse.

PMID- 12503606
TI  - Map kinase phosphatase-1 gene expression and regulation in neuroendocrine cells.
AB  - Long-term cellular processes like proliferation, differentiation, and adaptive
      responses (e.g. neuronal plasticity) are initiated by the synthesis of immediate
      early gene (IEG) products which control the expression of late response genes.
      Immediate early genes encode for transcription factors, structural proteins,
      cytokines, and other regulatory proteins. One of the latter category of IEG
      products is the mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1), a
      dual specificity tyrosine phosphatase which inactivates the MAP kinase ERK in the
      nucleus. In GH4C1 neuroendocrine cells, MKP-1 is rapidly synthesised and
      translocated to the nucleus in response thyrotropin-releasing hormone (TRH) or
      epidermal growth factor (EGF). Regulation of MKP-1 gene expression in this cell
      line is controlled at the transcriptional level via a strong block to elongation
      in the exon I of the gene. After stimulation with TRH the block to elongation is
      released and gene transcription is completed. Nuclear run-on is traditionally
      used to identify blocks to elongation and to determine endogeneous levels of
      transcriptional activities, but this method has severe technical limitations. An
      alternative approach to nuclear run-on is presented here for the MKP-1 gene,
      which involves the purification and analysis of nascent and free nuclear RNA
      fractions. [1] This method may be helpful to study in more detail the mechanisms
      of transcriptional elongation in mammalian cells.

PMID- 12503607
TI  - Synthetic retinoids dissociate coactivator binding from corepressor release.
AB  - The ligand-activated retinoid receptors RXR and RAR control development,
      homeostasis and disease by regulating transcription of retinoic acid (RA)
      responsive target genes or crosstalk with other signalling pathways. According to
      the current model ligand-binding triggers an exchange between corepressor- and
      coactivator-complexes that inhibit or potentiate transcription by deacetylating
      and acetylating nucleosomal histones, respectively. Additional cofactors may
      modify the transcriptional regulatory process by linking liganded retinoid
      receptors to structural components of chromatin or protein degradation. The
      desire to specifically influence defined events in RA-signalling, while others
      are left unaffected, motivated the synthesis of retinoid X receptors (RXR)- and
      retinoid acid receptors (RAR) isoform-selective retinoids. The present study
      investigates the potential of RARalpha isotype-specific synthetic agonists and
      antagonists to separate the processes of coactivator recruitment and corepressor
      release. The synthetic retinoids studied fall into four categories, two of which
      work according the above model, since they induce surfaces within the RARalpha
      ligand binding domain (LBD) suitable for either corepressor or coactivator
      interaction; these retinoids act as pure antagonists and pure agonists,
      respectively. In contrast, another type of retinoid induces a structure that
      allows for both, the interaction with corepressors and coactivators (partial
      RARalpha agonist), and exerts a cell context-specific (ant)agonistic activity.
      Finally, another type of retinoid, which cannot activate transcription itself but
      renders heterodimeric RARalpha permissive for signaling by RXR agonists inhibits
      both, corepressor and coactivator interaction (partial antagonist). Moreover,
      this retinoid discriminates between the nuclear corepressors SMRT and NCoR, since
      it efficiently dissociates SMRT but not NCoR from the RARalpha LBD.

PMID- 12503608
TI  - Genetic and biochemical studies of the Agouti-attractin system.
AB  - Pleiotropic effects of melanocortin signaling were first described nearly 100
      years ago when mice carrying the lethal yellow (A(y)) allele of the Agouti coat
      color gene were recognized to develop increased growth and adiposity. Work from
      our laboratory and others over the last several years has demonstrated that the
      non-pigmentary effects of A(y) are caused by ectopic expression of Agouti
      protein, a paracrine signaling molecule whose normal function is to inhibit
      signaling through the melanocortin 1 receptor (Mc1r), but which can mimic the
      effects of Agouti-related protein (Agrp), a homologous neuropeptide produced in
      the medial portion of the arcuate nucleus that acts as a potent antagonist of the
      Mc3r and Mc4r. Recently we have used the genetics of pigmentation as an in vivo
      screening system to analyze other mutations in the Agouti-melanocortin pathway,
      leading to the identification of Attractin (Atrn), a widely expressed type I
      transmembrane protein that serves as an accessory receptor for Agouti protein.
      Surprisingly, homologs of Atrn are found in fruitflies and nematodes, even though
      Agouti and/or Agouti-related protein are found only in vertebrates. Insight into
      this apparent paradox now comes from studies of different Atrn alleles, in which
      we find hyperactivity, abnormal myelination, and widespread CNS vacuolation. We
      suggest that the neurodegenerative phenotype reflects the ancestral function of
      Atrn to facilitate and/or maintain cell-cell interactions in the nervous system.
      Expression in neurectodermal cells during vertebrate evolution may have allowed
      Atrn to be recruited by the Agouti-melanocortin system to control coat color.

PMID- 12503609
TI  - Characterization of the human adenylyl cyclase gene family: cDNA, gene structure,
      and tissue distribution of the nine isoforms.
AB  - The membrane-bound adenylyl cyclases (ACs) represent one of the major families of
      effector enzymes for G protein-coupled receptors. Eight human AC isoforms,
      encoded by separate genes, have been identified up to now. However, in several
      cases only partial cDNA sequences are available (ADCY1,2,5). A ninth expected
      isoform, the human ortholog of rat ADCY4, has not been described yet. Using the
      high inter-species homology of mammalian AC isoforms, we searched the human
      genome and we succeeded to identify full-length coding sequences for all enzymes.
      Where required, missing sequence information was provided experimentally.
      Analysis of genomic sequences from the Celera database also allowed us to
      determine the exon-intron boundaries for ADCY1-9 and to establish the gene
      structures. We found that human AC genes comprise 11 to 26 exons, which are
      distributed over 16 to 430kb. We further report expression profiles for the nine
      ACs in a panel of 16 human tissues and in human embryonic kidney (HEK) cells.

PMID- 12503610
TI  - Homologous regulation of melanocortin-1 receptor (MC1R) expression in melanoma
      tumor cells in vivo.
AB  - As G protein-coupled receptors (GPCRs) are the target of numerous signaling
      molecules, including about half of the therapeutic drugs currently used, it is
      important to understand the consequences of homologous (ligand-induced) receptor
      regulation. Continuous exposure of GPCRs to agonist in vitro most frequently
      results in receptor down-regulation, but receptor up-regulation may occur as
      well. These phenomena are expected to play a role in the physiological adaptation
      to endogenous ligands and also in the response to repetitive administration of
      drugs in the clinic. However, there is little information on homologous
      regulation of GPCRs in vivo. Here, we report on the regulation of melanocortin-1
      receptor (MC1R) expression in melanoma cells implanted into mice. Two melanoma
      cell lines were investigated, D10 and B16F1, which in vitro had previously been
      shown to undergo homologous receptor up- and down-regulation, respectively. After
      implantation into mice and exposure to the natural MC1R agonist alpha-melanocyte
      stimulating hormone (alpha-MSH), cell-surface MC1R expression was evaluated by
      competition binding experiments in tumor membrane preparations. In B 16F1 cells,
      a single injection of 50 to 500 microg alpha-MSH induced a rapid but moderate
      dose-dependent MC1R down-regulation which could be totally reverted within 16-24
      h. By continuous administration of alpha-MSH via osmotic minipumps, MC1R down
      regulation was considerably amplified and reached the level observed in vitro,
      demonstrating that prolonged receptor interaction was necessary to induce a
      maximal effect in vivo. Similar results were obtained in vitro, which
      demonstrates that homologous MC1R regulation in B16F1 cells is essentially
      independent of the physiological environment. In D10 cells, however, up
      regulation could not be reproduced in vivo, suggesting that MC1R up-regulation is
      more dependent on the physiological environment. These results demonstrate the
      importance of in vivo receptor regulation studies, in particular in view of the
      potential use of MC1R as a target for melanoma therapy.

PMID- 12503611
TI  - Synthesis and in vitro and in vivo evaluation of [11C]methyl-BIII277CL for
      imaging the PCP-binding site of the NMDA receptor by pet.
AB  - A new benzomorphane derivative, [11C]methyl-BIII277CL, was evaluated as a
      potential radiotracer for visualizing the PCP-binding site of the N-methyl-D
      aspartate (NMDA) receptor by positron emission tomography (PET). Methyl-BIII277CL
      was prepared by reacting the desmethyl compound (BIII277CL) with dimethylsulfate.
      The pharmacological profile of methyl-BIII277CL was determined by in vitro
      receptor-screening assays. At a concentration of 100 nM, methyl-BIII277CL showed
      a significant interaction with the PCP-binding site of the NMDA receptor (79%
      inhibition of specific binding) and the sigma-binding site (46% inhibition). In
      displacement assays using mice cortical membranes, methyl-BIII277CL displayed a
      high affinity at the PCP-binding site of the NMDA receptor (Ki = 49 +/- 14
      nmol/L) and a 130-fold lower interaction with the sigma1-binding site (Ki = 6.35
      +/- 0.26 micromol/L). For saturation experiments and in vivo studies, methyl
      BIII277CL was radiolabeled with 11C at the O-position of the desmethyl precursor
      (BIII277CL) using [11C]methyliodide with a specific activity of 35-70
      GBq/micromol at the end of synthesis (EOS). In saturation assays using rat whole
      brain membranes [11C]methyl-BIII277CL showed a Kd of 6 +/- 1 nmol/L and a Bmax of
      670 +/- 154 fmol/mg protein. Biodistribution and PET studies in rats and pigs,
      however, indicated a lack of specific binding and unfavorable pharmacokinetics.
      Kinetic modeling using the 1-tissue compartment model demonstrated for
      [11C]methyl-BIII277CL a low distribution volume (Dv = 0.98 mL/mL(tissue)) and
      very high values for the kinetic parameters K1 and k2 (K1 = 0.36
      mL/mL(tissue)/min and k2 = 0.37min(-1)) in pig cortex. [11C]methyl-BIII277CL, due
      to the lack of specificity in vivo, may not be a candidate for imaging the PCP
      binding site of the NMDA receptor.

PMID- 12503612
TI  - Methodology and problems of protein-ligand docking: case study of dihydroorotate
      dehydrogenase, thymidine kinase, and phosphodiesterase 4.
AB  - The docking methodology was applied to three different therapeutically
      interesting enzymes: human dihydroorotate dehydrogenase (DHODH), Herpes simplex
      virus type I thymidine kinase (HSV1 TK) and human phosphodiesterase 4 (PDE4).
      Programs FlexX, AutoDock and DOCK where used. The three targets represent three
      distinct cases. For DHODH and HSV1 TK, the binding modes of substrate and
      inhibitors within the active site are known, while the binding orientation of
      cAMP within PDE4 has been solely hypothesized. Active site of DHODH is mainly
      hydrophobic and the binding mode of the inhibitor brequinar was used as a
      template for evaluating the docking strategies. The presence of cofactors
      revealed to be crucial for the definition of the docking site. The HSV1 TK active
      site is small and polar and contains crystal water molecules and ATP. Docking of
      thymidine and aciclovir (ACV) within the active site was analyzed by keeping or
      removing water molecules. It showed the crucial role of water in predicting the
      binding of pyrimidines and purines. The crystal structure of PDE4 contains
      magnesium and zinc cations as well as catalytic water molecule but no ligand.
      Several docking experiments of cAMP and rolipram were performed and the results
      showed clear-cut dependence between the ligand orientation and the presence of
      metals in the active site. All three cases show specific problems of the docking
      methodology, depending on the character of the active site.

PMID- 12503613
TI  - Urotensin II mediates ERK1/2 phosphorylation and proliferation in GPR14
      transfected cell lines.
AB  - Urotensin-II (U-II), a vasoactive cyclic neuropeptide, was recently identified as
      the natural ligand for the G-protein coupled receptor GPR14. The expression
      pattern of U-II and GPR14 are consistent with a role as a neurohormonal
      regulatory system in cardiovascular homeostasis. Urotensin-II induces a rapid and
      short-lasting rise in intracellular calcium in recombinant GPR14 expressing
      cells. In the present study we show that U-II induces signal transduction
      pathways leading to the long-lasting activation of extracellular signal-regulated
      kinase 1/2 (ERK1/2) in chinese hamster ovary cells expressing human GPR14 (CHO
      GPR14). Furthermore, we observed a growth-stimulating and PD98059 sensitive
      activity of U-II in CHO-GPR14 cells, but not CHO-K1 cells. The investigation of
      the GPR14 induced signal transduction pathways leading to ERKI/2 phosphorylation
      revealed a previously unsuspected role for G(i/o)-protein coupling and showed an
      involvement of phospatidylinositol-3-kinase, phospholipase C and calcium channel
      mediated mechanisms. Our results suggest that U-II and its receptor GPR14 may be
      involved in long-lasting physiological effects such as cardiovascular remodeling.

PMID- 12503614
TI  - Analysis of ligand-receptor interactions in cells by atomic force microscopy.
AB  - Atomic force microscopy (AFM) increasingly has been used to analyse "receptor"
      function, either by using purified proteins ("molecular recognition microscopy")
      or, more recently, in situ in living cells. The latter approach has been enabled
      by the use of a modified commercial AFM, linked to a confocal microscope, which
      has allowed adhesion forces between ligands and receptors in cells to be measured
      and mapped, and downstream cellular responses analysed. We review the application
      of AFM to cell biology and, in particular, to the study of ligand-receptor
      interactions and draw examples from our own work and that of others to show the
      utility of AFM, including for the exploration of cell surface functionalities. We
      also identify shortcomings of AFM in comparison to "standard" methods, such as
      receptor auto-radiography or immuno-detection, that are widely applied in cell
      biology and pharmacological analysis.

PMID- 12503615
TI  - Specific stimulation of migration of human keratinocytes by mu-opiate receptor
      agonists.
AB  - There are several indications that neuropeptides, especially the opiate receptor
      agonists, modulate the immune response by stimulating the formation of
      granulation tissue and enhancing the reepithelialization. We observed that the mu
      opiate receptor ligand beta-endorphin stimulates the migration of cultured human
      foreskin keratinocytes. After 1 hour exposure to 1 microM beta-endorphin, the
      keratinocytes experienced an increase of cell diameter by cellular elongation and
      stimulation of migration. Dynorphin had a lesser effect under the same condition.
      The opiate receptor antagonist naltrexone significantly reduced the effect of
      beta-endorphin on keratinocyte migration. This migratory effect of mu-opiate
      receptor agonists in vitro indicates that the opioid peptides, released in
      wounds, could play a key role in the final reepithelialization and tissue
      regeneration in wound healing. This new knowledge will help us not only to
      understand the mechanism of wound healing but also to improve the therapeutic
      strategy in the healing of painful chronic wounds.

PMID- 12503616
TI  - Remodeling of Na,K-ATPase, and membrane fluidity after atrial fibrillation in
      sheep.
AB  - Atrial fibrillation (AF) is accompanied by various changes in ion channels that
      cause atrial electrophysiological remodeling. The enzyme Na,K-ATPase is also a
      major cellular mechanism for the regulation of ion homeostasis. During AF, Na,K
      ATPase may be regulated by synthesis of its alpha- and beta-subunits as well as
      changes in membrane fluidity. To test this hypothesis, we studied the effect of
      pacing-induced AF in sheep on atrial Na,K-ATPase alpha- and beta-subunits and on
      membrane fluidity as well. METHODS: A group of six sheep (AF group) was subjected
      to overdrive electrical stimulation of the right atrium in order to induce AF. A
      group of six sham operated sheep served as control. All paced sheep developed
      multiple episodes of sustained AF with a mean total duration of 110 min over a 2
      hours period. Protein expression of Na,K-ATPase alpha- and beta-subunits in
      atrial microsomal membranes was assayed by Western blotting analysis. When
      significant changes in membrane expression were observed, transcriptional
      regulation was analysed by Northern blotting. Membrane fluidity was assessed on
      atrial microsomal fractions by anisotropy measurements using the fluorescent
      probe diphenylhexatriene. RESULTS: Atrial fibrillation enhanced the expression of
      the Na,K-ATPase beta1-subunit at both membrane and mRNA levels. Anisotropy values
      were higher in AF group than in control group, indicating a decreased fluidity of
      the membranes isolated from paced sheep atria. CONCLUSION: These data are the
      first evidence for an enhanced Na,K-ATPase beta1-subunit expression in membrane
      during AF. Membrane rigification represents a new factor of tachycardia-induced
      atrial remodeling.

PMID- 12503617
TI  - Mono- or dual-phosphorylation of akt kinase is regulated by distinct receptors
      that involve the common insulin receptor substrate.
AB  - We have previously shown that the interleukin (IL)-4 signal transduction involves
      the Insulin Receptor Substrate (IRS) in human colorectal carcinoma cells LS513.
      In the present study it was tested whether IL-4 counters Insulin-like Growth
      Factor (IGF)-1 through competition at the IRS signal transduction pathway and,
      thus, induces a molecular "insulin resistance" or whether IL-4 invokes an
      alternative signal transduction. The activated receptors of IL-4 and IGF-I both
      docked to IRS-1 and IRS-2 and invoked IRS complex formation with
      phosphatidylinositol (PI) 3-kinase, as assessed by immunoprecipitation and
      detection of the precipitated compounds by immunoblot analysis. Both, IL-4 and
      IGF-1, signaling pathways induced phosphorylation of Akt kinase in a PI 3-kinase
      dependent manner, as assessed by addition of the PI 3-kinase inhibitor Ly294002.
      Interleukin-4 stimulation induced mono-phosphorylation at serine residue S473 of
      Akt kinase but failed to activate the kinase. Insulin-like growth factor-1
      stimulation invoked dual-phosphorylation at S473 and T308 of Akt kinase and
      subsequent activation of the kinase. When LS513 cells were treated with IL-4 to
      induce mono-phosphorylation of Akt, dual- phosphorylation and activation of Akt
      kinase in response to IGF-1 were still intact. Interleukin-4 yet reduced cell
      growth by at least 50% both, in the absence and presence of growth factor IGF-1.
      In the LS513 cells, IL-4 stimulated phosphorylation of Jak2, an adapter molecule
      at the IL-4 receptor, and phosphorylation of transcription factor Stat6 both, in
      the absence and presence of IGF-1. We found a similar IL-4 signal transduction
      and growth suppression in multiple human cell cultures, including primary cells.
      Our findings indicate that the molecular mechanism underlying growth suppression
      by IL-4 may depend on gene-expression but not on "insulin/growth factor
      resistance" at IRS.

PMID- 12503618
TI  - Semliki forest virus-based expression for versatile use in receptor research.
AB  - Semliki Forest virus (SFV) vectors have been generated for highly efficient
      studies on gene expression in a variety of mammalian host cells, including
      immortalized cell lines as well as primary cells in culture. Moreover, SFV
      expression has been scaled up for mammalian suspension cultures in spinner flasks
      and bioreactors for production of large quantities of recombinant proteins for
      drug screening and purification. The strong preference of expression in neuronal
      cells in primary cell cultures, in organotypic hippocampal slices and in vivo has
      made SFV vectors attractive for neurobiological studies. Additionally, the
      engineering of novel, less cytotoxic and temperature-sensitive SFV mutant vectors
      has further increased their application range.

PMID- 12503619
TI  - Novel method for the study of receptor Ca2+ signalling exemplified by the NK1
      receptor.
AB  - We have used a novel technology (NovoStar from BMG Labtechnologies) for the study
      of the Ca2+ signalling of the human tackykinin NK1 (hNK-I receptor). The NovoStar
      is a microplate reader based on fluorescence and luminescence. The instrument
      implements a robotic pipettor arm and two microplate carriers, typically one for
      samples and one for cells. The robotic pipettor arm can transfer sample (agonist
      or antagonist) from the sample plate or other liquid containers to the cell
      plate, facilitating the study of Ca2+ signalling to such a degree that the
      instrument can be used for Medium Throughput Screening (MTS). Using the NovoStar
      we have found the molecular pharmacology of the NK1 receptor to be comparable to
      that observed in classical signal transduction assays. Thus, we have observed an
      EC50 value of 3 nM for substance P induced Ca2+ response. This value corresponds
      well with previously published values for substance P induced IP and cAMP
      turnover. [1] Using the NovoStar technology we have studied the pharmacological
      profile of the well known non-peptide NKI receptor antagonists CP96,345 and
      SR140,333 [2,3] in respect of inhibition of the Ca2+ response induced by
      substance P. Interestingly, the antagonistic potency of the antagonists depended
      greatly on the experimental design, e.g., a dependency of timing in the addition
      of antagonists vs. agonist was noted. Also, metal-ion site engineered NK1
      receptors [2] were tested for the ability of metal-ions to inhibit signalling. It
      is concluded that the NovoStar is a reliable tool for the study of receptor Ca2+
      signalling, both as a research tool and as a MTS system.

PMID- 12503620
TI  - Structure of GABAB receptors in rat retina.
AB  - In the search for yet unknown subtypes of GABAB receptors, the subunit
      architecture of GABAB receptors in the retina was analyzed using selective
      antisera. Immunopurification of the splice variants GABAB1a and GABAB1b
      demonstrated that both were associated with GABAB2. Quantitative
      immunoprecipitation experiments indicated that practical the entire GABAB
      receptor population in the retina consists of the receptor subtypes
      GABAB1a/GABAB2 and GABAB1b/GABAB2, although low levels of GABAB1c/GABAB2 cannot
      be excluded. The data rule out the existence of GABAB receptors containing the
      splice variants GABAB1d and GABAB1e. Moreover, no evidence for homomeric GABAB1
      receptors was found. Among the splice variants, GABAB1a is by far the predominant
      one in neonatal and adult retina, whereas GABAB1b is expressed only late in
      postnatal development and in the adult retina. Since GABAB1a is expressed at high
      levels before functional synapses are formed, this specific receptor subtype
      might be involved in the maturation of the retina. Finally, subcellular
      fractionation demonstrated that GABAB1a, but not GABAB1b, is present in
      postsynaptic densities, suggesting a differential pre- and postsynaptic
      localisation of both splice variants.

PMID- 12503621
TI  - Potentiation of GPCR-signaling via membrane targeting of G protein alpha
      subunits.
AB  - Different assay technologies are available that allow ligand occupancy of G
      protein coupled receptors to be converted into robust functional assay signals.
      Of particular interest are universal screening systems such that activation of
      any GPCR can be detected with a common assay end point. The promiscuous G protein
      Galpha16 and chimeric G proteins are broadly used tools for setting up almost
      universal assay systems. Many efforts focused on making G proteins more
      promiscuous, however no attempts have been made to make promiscuos G proteins
      more sensitive by interfering with their cellular protein distribution. As a
      model system, we used a promiscuous G protein alphaq subunit, that lacks the
      highly conserved six amino acid N-terminal extension and bears four residues of
      alphai sequence at its C-terminus replacing the corresponding alphaq sequence
      (referred to as delta6qi4). When expressed in COS7 cells, delta6qi4 undergoes
      palmitoylation at its N-terminus. Cell fractionation and immunoblotting analysis
      indicated localization in the particulate and cytosolic fraction. Interestingly,
      introduction of a consensus site for N-terminal myristoylation (the resulting
      mutant referred to as delta6qi4myr) created a protein that was dually acylated
      and exclusively located in the particulate fraction. As a measure of G protein
      activation delta6qi4 and delta6qi4myr were coexpressed (in CHO cells) with a
      series of different Gi/o coupled receptors and ligand induced increases in
      intracellular Ca2+ release were determined with the FLIPR technology
      (Fluorescence plate imaging reader from Molecular Devices Corp.). All of the
      receptors interacted more efficiently with delta6qi4myr as compared with
      delta6qi4. It could be shown that increased functional responses of agonist
      activated GPCRs are due to the higher content of delta6qi4myr in the plasma
      membrane. Our results indicate that manipulation of subcellular localization of G
      protein alpha subunits-moving them from the cytosol to the plasma membrane
      potentiates signaling of agonist activated GPCRs. It is concluded that addition
      of myristoylation sites into otherwise exclusively palmitoylated G proteins is a
      new and sensitive approach and may be applicable when functional assays are
      expected to yield weak signals as is the case when screening extracts of tissues
      for biologically active GPCR ligands.

PMID- 12503622
TI  - DEPD, a high resolution gene expression profiling technique capable of
      identifying new drug targets in the central nervous system.
AB  - Digital expression pattern display (DEPD) is an open, automated, PCR-based system
      of gene expression profiling that is capable of resolving as many as 100,000
      transcripts from a single brain tissue cDNA sample. It has a detection
      sensitivity of better than 1 in 750,000 and it can reliably detect differences in
      RNA expression levels of less than two-fold. Digital expression pattern display
      presently is the most sensitive and therefore the only expression profiling
      method available that is capable of monitoring, in a semi-quantitative fashion,
      the expression of even the rarest of transcripts found in human brain tissue.
      Biofrontera applies this proprietary technique, together with state-of-the-art
      bioinformatics, for the purposes of elucidating pathology pathways of major brain
      diseases, of analysing the target profiles of drugs presently applied or in
      development, and of identifying novel targets for drug action.

PMID- 12503623
TI  - Methionine proximity assay, a novel method for exploring peptide ligand-receptor
      interaction.
AB  - Probing G-protein coupled receptor (GPCR) structures is a priority in the
      functional and structural understanding of GPCRs. In the past, we have used
      several approaches around photoaffinity labeling in order to establish contact
      points between peptide ligands and their cognate receptors. Such contact points
      are helpful to build reality based molecular models of GPCRs and to elucidate
      their activation mechanisms. Most studies of peptidergic GPCRs have been done
      with photolabeling peptides containing the benzophenone moiety as a reputedly non
      selective probe. However our recent results are now showing that p
      benzoylphenylalanine (Bpa) has some selectivity for Met residues in the receptor
      protein, reducing the accuracy of this method. Turning a problem into an asset,
      modified analogues of Bpa, e.g. p,p'-nitrobenzoylphenylalanine (NO2Bpa), display
      increased selectivity for such Met residues. It means a photoprobe containing
      such modified benzophenone-moieties does not label a receptor protein unless a
      Met residue is in the immediate vicinity. This unique property allows us to
      propose and show the feasibility and utility of a new method for scanning the
      contact areas of peptidergic GPCRs, the Methionine Proximity Assay (MPA).
      Putative contact residues of the receptor are exchanged to Met residues by site
      directed mutagenesis and are subjected to photoaffinity labeling with such
      modified benzophenone-containing peptides. Successful incorporation indicates
      physical proximity of those residues. This principle is established and explored
      with benzophenone-containing analogues of angiotensin II and the two known human
      angiotensin II receptors AT1 and AT2, determining contact points in both
      receptors. This approach has several important advantages over other scanning
      approaches, e.g., the SCAM procedure, since the MPA-method can be used in the
      hydrophobic core of receptors.

PMID- 12503624
TI  - Tetraethylammonium binding to the outer mouth of the KcsA potassium channel:
      implications for ion permeation.
AB  - Extracellular tetraethylammonium (TEA+) inhibits the current carried out by K+
      ions in potassium channels. Structural models of wild-type (WT) and Y82C KcsA K+
      channel/TEA+ complexes are here built using docking procedures, electrostatics
      calculations and molecular dynamics simulations. The calculations are based on
      the structure determined by Doyle et al. (11) Our calculations suggest that in
      WT, the TEA+ cation turns binds at the outer mouth of the selectivity filter,
      stabilized by electrostatic and hydrophobic interactions with the four Tyr82 side
      chains. Replacement of Tyr82 with Cys causes a decrease of the affinity of the
      cation for the channel, consistently with the available site-directed mutagenesis
      data (16). An MD simulation in which K+ replaces TEA+ provides evidence that TEA+
      binding site can accommodate a potassium ion, in agreement with the high
      resolution structure recently reported by Zhou et al. (20)

PMID- 12503625
TI  - Use of fluorescence polarization detection for the measurement of fluopeptidetm
      binding to G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) represent the single largest molecular target
      of therapeutic drugs currently on the market, and are also the most common target
      in high throughput screening assays designed to identify potential new drug
      candidates. A large percentage of these assays are now formatted as radioligand
      binding assays. Fluorescence polarization ligand binding assays can offer a non
      rad alternative to radioligand binding assays. In addition, fluorescence
      polarization assays are a homogenous format that is easy to automate for high
      throughput screening. We have developed a series of peptide ligands labeled with
      the fluorescent dye BODIPY TMR whose binding to GPCRs can be detected using
      fluorescence polarization methodology. BODIPY TMR has advantages over the more
      commonly used fluorescein dye in high throughput screening (HTS) assays due to
      the fact that its excitation and emission spectra are red-shifted approximately
      50 nm relative to fluorescein. Assays based on BODIPY TMR ligands are therefore
      less susceptible to interference from tissue auto-fluorescence in the assay
      matrix, or the effects of colored or fluorescent compounds in the screening
      libraries. A series of BODIPY TMR labeled peptides have been prepared that bind
      to a range of GPCRs including melanin concentrating hormone, bradykinin, and
      melanocortin receptors. Conditions have been optimized in order to utilize a
      comparable amount of receptor membrane preparation as is used in a radioligand
      binding assay. The assays are formatted in 384-well microplates with a standard
      volume of 40 microL. We have compared the assays across the different
      fluorescence polarization (FP) readers available to determine the parameters for
      each instrument necessary to achieve the required precision.

PMID- 12503626
TI  - Affinity labeling of cysteine-mutants evidences contact residues in modeled
      receptor binding sites.
AB  - To investigate the topology of binding sites in two ionotropic receptors, we have
      initiated a strategy combining affinity labeling with cysteine-scanning
      mutagenesis. For the GABAA receptor we have used reactive derivatives of non
      competitive blockers (NCBs) to explore interacting positions in its channel. The
      polypeptide positions of the M2 segment of the alpha1 subunit which we mutated
      into cysteine were selected for their established accessibility, as determined by
      the substituted-cysteine accessibility method (SCAM). Using the Xenopus oocyte
      expression system, we show that receptors containing mutations V257C and S272C
      are inactivated by several reactive NCBs. These position-selective inactivations
      lead to an analysis of NCB binding in the channel. For the NMDA receptor glycine
      binding site, the prototype antagonist L-701,324 was derivatized at different
      positions with different reactive groups. The receptor positions to mutate into
      cysteine were selected after a 3-D homology model. The observed receptor
      inactivations are mutant- and probe-selective, leading to an unambiguous chemical
      docking of the antagonist pharmacophore and supporting the model. The site
      specificity of the inactivating reactions is assessed by protection experiments
      and by mutant to wild-type (WT) comparisons. The scope and limitations of the
      method are briefly discussed.

PMID- 12503627
TI  - A stopped-flow fluorescence anisotropy method for measuring hormone binding and
      dissociation kinetics with cell-surface receptors in living cells.
AB  - We have developed a system for extending stopped-flow analysis to the kinetics of
      ligand capture and release by cell surface receptors in living cells. While most
      mammalian cell lines cannot survive the shear forces associated with turbulent,
      stopped-flow mixing, we determined that 32D cells, murine hematopoietic precursor
      cells, can survive rapid mixing, even at the high flow rates necessary to achieve
      dwell times as short as 10 msec. In addition, 32D cells do not express any member
      of the ErbB family of receptors, providing a null background for studying this
      receptor family. We have established a series of stable, monoclonal 32D-derived
      cell lines that express the epidermal growth factor (EGF) receptor, ErbB2, or a
      combination of both at different ratios. Using these cell lines and a homogeneous
      fluorescent derivative of H22Y-mEGF modified with fluorescein at the amino
      terminus (F-EGF), we have measured association and dissociation of F-EGF with its
      receptor. Association was measured by following the time-dependent changes in
      fluorescence anisotropy after rapidly mixing cells at various cell densities with
      F-EGF at 1-15nM. Dissociation was measured both by chase experiments in which
      unlabeled EGF was mixed with cells pre-equilibrated with F-EGF or by dilution of
      cells equilibrated with F-EGF. Comparison of these dissociation experiments
      demonstrated that little or no ligand-induced dissociation occurs in the chase
      dissociation experiments. For each cell line, data from a series of association
      experiments and dilution dissociation experiments were subjected to global
      analysis using a two independent receptor-class model. Our analysis is consistent
      with the presence of two distinct receptor populations, even in cells bearing
      only the EGF receptor. Increasing the relative expression of ErbB2 leads to an
      increase in the fraction of high affinity class receptors observed, without
      altering the total number of EGF binding sites.

PMID- 12503628
TI  - The use of phage display in the study of receptors and their ligands.
AB  - Phage display technology presents a rapid means by which proteins and peptides
      that bind specifically to predefined molecular targets can be isolated from
      extremely complex combinatorial libraries. There are several important ways by
      which phage display can provide impetus to receptor-based research. Firstly,
      phage display can be applied, alongside transcriptome and proteome expression
      profiling techniques, to the identification and characterisation of receptors
      whose expression is specific to either a cell lineage, a tissue or a disease
      state. Secondly, specific monoclonal antibodies that enable researchers to
      identify, localize and quantify receptors can be produced very rapidly (weeks).
      Thirdly, it should be possible to apply phage display to the matching of orphan
      ligands and receptors. Finally, phage display can be used to identify proteins
      and peptides that modulate receptor activity. As well as being useful in the
      study of receptor function, biologically active proteins and peptides could also
      be used therapeutically, or as leads for drug design. Hence phage display is
      ready to play a central role in the study of receptors in the post-genome era.
      This review outlines the ways in which phage display has been applied to the
      study of receptor-ligand systems, and discusses how new developments in the
      technology may be of even greater utility to the field in the next decade.

PMID- 12503629
TI  - Docking ligands to vasopressin and oxytocin receptors via genetic algorithm.
AB  - The aim of the study was to computer-dock selected ligands to neurophyseal
      receptors in order to identify amino acid residues responsible for ligand
      receptor interactions. To this aim, reliable oxytocin receptor (OTR) and arginine
      vasopressin receptor (V1aR/V2R) models were built. The OTR-selective agonist
      [Thr4,Gly7]OT, the OTR-selective cyclohexapeptide antagonist L-366,948 and OT
      itself were docked via genetic algorithm to OTR, V1aR, and V2R and relaxed using
      a constrained simulated annealing protocol. For the analysis of receptor/ligand
      interactions a subset of initial conformations was chosen using energetic and
      steric criteria. All three ligands seem to prefer similar modes of binding to the
      receptors, manifested by repetitive residues of the receptors which directly
      interact with the ligands. Taking into account that many aspects of mechanisms of
      G protein-coupled receptor (GPCR) action are still unsolved, the results obtained
      with the docking simulations may propose future experimental research, especially
      in site-directed mutagenesis analysis and searching for key amino acid residues
      responsible for drug activities.

PMID- 12503630
TI  - Affinities of gidazepam and its analogs for mitochondrial benzodiazepine
      receptors.
AB  - Mitochondrial benzodiazepine receptors (MBRs) participate in many physiological
      processes, such as calcium flow regulation, proliferative and respiratory cell
      functions, mitochondrial steroidogenesis and adaptational reactions to stress. We
      have found that the selective anxiolytic gidazepam has a higher affinity for CNS
      MBRs as compared to central benzodiazepine receptors. The ability of gidazepam to
      bind to MBRs probably underlies a wide spectrum of its pharmacological effects.
      We have studied affinities of gidazepam analogs for CNS MBRs in search for the
      ligands possessing higher affinity and selectivity. The experiments were carried
      out with male Wistar rats weighing between 200-220 g. Affinities of the
      investigated compounds were assessed on their ability to displace radioligand Ro5
      4864 from its specific binding sites on MBRs of rat brain. Within the series of
      tested compounds three substances comparable on affinity with Ro5-4864 were
      found. Experimental results have shown that the presence of chlorine atom in o
      position of 5-phenyl substituent leads to a 10 to 15-fold increase in affinity
      for CNS MBRs. We have also found that the essential contribution in affinity of
      the investigated series is brought by lipophilicity of substituent in IN
      position. Our data may be useful in design and synthesis of novel potent
      selectively acting ligands of CNS MBRs.

PMID- 12503631
TI  - Molecular and pharmacological characterisation of the MSH-R alleles in Swiss
      cattle breeds.
AB  - The coat colour in mammals is determined by the relative amounts of eumelanin
      (black/brown) and phaeomelanin (red/yellow), produced in melanocytes, which are
      controlled by melanocyte stimulating hormone receptor (MSH-R). Melanocyte
      stimulating hormone receptor is activated by alpha-melanocyte-stimulating hormone
      (alpha-MSH). Stimulated MSH-R activates adenylyl cyclase (AC), thereby increasing
      the amount of cyclic AMP in the cell, which activates the enzyme tyrosinase
      resulting in eumelanin synthesis. In this study the complete coding sequences of
      five alleles of the MSH-R gene found in Holstein, Red Holstein, Simmental, and
      Brown Swiss cattle were cloned into a mammalian expression vector and transfected
      into human embryonic kidney (HEK) 293 cells. The expressed receptors were
      analyzed for their ability to increase intracellular cAMP in response to
      stimulation by alpha-MSH. The recessive red allele (e) found in Red Holstein and
      Simmental and the dominant black allele (ED) found in Holstein were unresponsive
      to a wide range of alpha-MSH concentrations. Two alleles from Brown Swiss (E(d1),
      E(d2)) and one allele found in the Simmental breed (e(f)) responded to
      stimulation by alpha-MSH in a dose-dependent manner. When compared to E(d1) and
      E(d2), the cells transfected with the e(f) MSH-R allele, however, reached the
      corresponding intracellular cAMP concentrations at a 10-fold higher concentration
      of alpha-MSH. In conjunction with the mode of inheritance of coat colour, the
      results indicate that the e MSH-R allele is a non-functional receptor, E(D) is
      constitutively activated receptor, and E(d1) and E(d2) are hormonally activated
      receptors. The delay in e(f) MSH-R response may explain the similarity between
      the e and e(f) phenotypes.

PMID- 12503632
TI  - Identification of a histamine H4 receptor on human eosinophils--role in
      eosinophil chemotaxis.
AB  - Eosinophils are recruited to sites of inflammation via the action of a number of
      chemical mediators, including PAF, leukotrienes, eotaxins, ECF-A and histamine.
      Although many of the cell-surface receptors for these mediators have been
      identified, histamine-driven chemotaxis has not been conclusively attributed to
      any of the three known histamine receptor subtypes, suggesting the possibility of
      a 4th histamine-responsive receptor on eosinophils. We have identified and cloned
      a novel G protein-coupled receptor (GPCR), termed Pfi-013, from an IL-5
      stimulated eosinophil cDNA library which is homologous to the human histamine H3
      receptor, both at the sequence and gene structure level. Expression data
      indicates that Pfi-013 is predominantly expressed in peripheral blood leukocytes,
      with lower expression levels in spleen, testis and colon. Ligand-binding studies
      using Pfi-013 expressed in HEK-293Galpha15 cells, demonstrates specific binding
      to histamine with a Kd of 3.28 +/- 0.76 nM and possesses a unique rank order of
      potency against known histaminergic compounds in a competitive ligand-binding
      assay (histamine > clobenpropit > iodophenpropit > thioperamide > R-alpha
      methylhistamine > cimetidine > pyrilamine). We have therefore termed this
      receptor human histamine H4. Chemotaxis studies on isolated human eosinophils
      have confirmed that histamine is chemotactic and that agonists of the known
      histamine receptors (H1, H2, and H3) do not induce such a response. Furthermore,
      studies employing histamine-receptor antagonists have shown an inhibition of
      chemotaxis only by the H3 antagonists clobenpropit and thioperamide. Since these
      compounds are also antagonists of hH4 we postulate that the receptor mediating
      histaminergic chemotaxis is this novel histamine H4 receptor.

PMID- 12503633
TI  - The influence of coumestrol, zearalenone, and genistein administration on insulin
      receptors and insulin secretion in ovariectomized rats.
AB  - The influence of phytoestrogens (genistein and coumestrol) and mycoestrogen
      (zearalenone) on insulin secretion, liver insulin receptors and some aspects of
      lipid and carbohydrate metabolism were investigated in this study. Ovariectomized
      rats were injected s.c. with the above mentioned compounds in the amount of 1 mg
      for three days. Coumestrol and zearalenone caused a significant increase in
      uterus weight, similar to the effects observed after estrone action, while this
      effect was not observed after the genistein injection. Blood insulin level was
      not changed after phyto- or mycoestrogen treatment. However, coumestrol and
      genistein significantly decreased the binding capacity of liver insulin
      receptors. These changes corresponded with alterations in glucose and free fatty
      acids profiles in blood, as well as with glycogen content in liver. The effects
      observed after genistein and coumestrol injections differed from those noticed in
      rats treated with zearalenone or estrone. On the basis of these results we
      conclude that metabolic effects of high doses of coumestrol and genistein in
      ovariectomized rats are partly mediated by changes in insulin sensitivity of the
      liver and that the action of plant estrogens on metabolism is, at least to the
      some degree, independent of their estrogen activity.

PMID- 12503634
TI  - Binding of [99mTc]chondroitin sulfate to scavenger receptors on human
      chondrocytes as compared to binding of oxidized [125I]LDL on human macrophages.
AB  - Chondroitin sulfate (CS) used for treatment of osteoarthritis exerts distinct
      effects on human articular chondrocytes in vitro. We performed a binding analysis
      with 99mTc-labeled CS (Condrosulf, a commercial CS preparation containing calcium
      stearate) and cultured human chondrocytes in order to evaluate the presence of
      specific receptors. Saturation binding at 37 degrees C for 2 h revealed the
      presence of high-affinity binding sites for CS with a Kd of 2.3 x 10(-9) mol/L
      and a Bmax of 5.0 x 10(8). Extensive dialysis of Chondrosulf led to a decrease of
      the binding affinity by 52.5 +/- 19.5% and of the number of CS binding sites/cell
      by 62.0 +/- 14.0%, demonstrating that the additive present in the Condrosulf
      preparation enhances CS binding. The nature of the binding site is not yet known
      but evidence exists in the literature that the scavenger receptor CD36,
      thoroughly investigated on macrophages, is also found on chondrocytes and might
      be involved in CS binding. Therefore, we undertook a comparative binding study
      with human monocytes and labelled LDL and oxidized LDL, the latter being a
      postulated atherogenic agent in atherosclerosis. For [125I]-LDL binding we found
      a Kd of 0.45 x 10(-8) mol/L and a Bmax of 0.14 x 10(6) on quiescent monocytes and
      for [125I]-(ox)LDL binding a Kd of 1.8 x 10(-8) mol/L and a Bmax of 1.3 x 10(6)
      using LPS-activated monocytes. These data are comparable to the binding affinity
      found for lipoprotein-proteoglycan-complexes and hence are an indication but not
      a proof that CD36 is involved in CS binding to human chondrocytes.

PMID- 12503635
TI  - Genetic approaches to the identification of interactions between membrane
      proteins in yeast.
AB  - The recent sequencing of entire eukaryotic genomes has renewed the interest in
      identifying and characterizing all gene products that are expressed in a given
      organism. The characterization of unknown gene products is facilitated by the
      knowledge of its binding partners. Thus, a novel protein may be classified by
      identifying previously characterized proteins that interact with it. If such an
      approach is carried out on a large scale, it may allow the rapid characterization
      of the thousands of predicted open reading frames identified by recent sequencing
      projects. Currently, the yeast two-hybrid system is the most widely used genetic
      assay for the detection of protein-protein interactions. The yeast two-hybrid
      system has become popular because it requires little individual optimization and
      because, as compared to conventional biochemical methods, the identification and
      characterization of protein-protein interactions can be completed in a relatively
      short time span. In this review, we briefly discuss the yeast two-hybrid system
      and its application to large scale screening studies that aim at deciphering all
      protein-protein interactions taking place in a given cell type or organism. We
      then focus on a class of proteins that is unsuitable for conventional yeast two
      hybrid systems, namely integral membrane proteins and membrane-associated
      proteins, and describe several novel genetic systems that combine the advantages
      of the yeast two-hybrid system with the potential to identify interaction
      partners of membrane-associated proteins in their natural setting.

PMID- 12503636
TI  - Nad-299 antagonises 5-HT-stimulated and spiperone-inhibited [35S]GTPgammaS
      binding in cloned 5-HT1A receptors.
AB  - In Chinese Hamster Ovary (CHO) cells expressing cloned human 5
      hydroxytryptamine1A A (5-HT1A) receptors, (R)-3-N,N-dicyclobutylamino-8-fluoro-[6
      3H]-3,4-dihydro-2H-1-benzopyan-5-carboxamide ([3H]NAD-299) exhibited high
      affinity (Kd = 0.16 nM) and labeled 34% more receptors than 8-hydroxy-2-([2,3
      3H]di-n-propylamino)tetralin ([3H]8-OH-DPAT). NAD-299 behaved as a silent
      antagonist in [35S]GTPgammaS binding similar to N-tert-butyl-3-(4-(2
      methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide (WAY-100635) and (S)-5-fluoro
      8-hydroxy-2-(di-n-propylamino)tetralin ((S)UH-301). 5-HT and 5
      carboxamidotryptamine (5-CT) stimulated [35S]GTPgammaS binding 2.5-fold while
      spiperone and methiothepin inhibited [35S]GTPgammaS binding 1.4-fold.
      Furthermore, NAD-299 antagonised both the 5-HT stimulated and the spiperone
      inhibited [35S]GTPgammaS binding to basal levels. The KiL/KiH ratios for
      spiperone (0.66), methiothepin (0.39), WAY-100635 (0.32), (S)UH-301 (0.94), NAD
      299 (1.29), NAN-190 (1.23), (S)pindolol (5.85), ipsapirone (13.1), buspirone
      (24.6), (+/-)8-OH-DPAT (47.3), flesinoxan (55.8), 5-HT (200) and 5-CT (389)
      correlated highly significantly with the intrinsic activity obtained with [35S]
      GTPgammaS (r = 0.97).

PMID- 12503637
TI  - A spin-column procedure for estrogen receptor equilibrium and competition binding
      analysis.
AB  - Estrogen receptors, members of the nuclear hormone receptor family, are not only
      able to bind their endogenous hormone, 17beta-estradiol, but can also accommodate
      other naturally-occuring, non-steroidal molecules. Here, we describe a spin
      column procedure to determine accurately equilibrium dissociation constants (Kds)
      and IC50 concentrations for estrogenic compounds. The human wild-type ERalpha was
      used to validate the protocol. We expressed the full-length ERalpha protein in an
      eukaryotic system to ensure all possible post-transcriptional modifications. The
      gel filtration-based assay revealed a temperature-dependent Kd shift for ERalpha.
      At physiological conditions (150 mM salt, 37 degrees C) we determined the 17beta
      estradiol Kd for ERalpha to be 281 +/- 13 pmol/L. Positive cooperativity was only
      apparent at low temperatures and diminished to zero at 37 degrees C. In
      homologous competition binding experiments using 17beta-estradiol, we observed
      fifty fold higher IC50 values than the respective Kd. This paper presents a
      reliable and sensitive protocol to generate saturation binding curves and
      heterologous competition curves to test estrogenic compounds.

PMID- 12503638
TI  - Expression of receptors for melanin-concentrating hormone (MCH) in different
      tissues and cell lines.
AB  - Melanin-concentrating hormone (MCH) is a potent orexigenic neuropeptide and a
      physiological antagonist of alpha-melanocyte-stimulating hormone (alpha-MSH) in
      the brain as well as at peripheral sites, including the pigmentary systems of
      specific vertebrates. Two receptor subtypes for MCH, MCH-R1 and MCH-R2, have been
      cloned, but other receptor subtypes are likely to exist. Based on our own data
      and the current literature, we have compared the expression of different
      receptors for MCH in various mammalian cell lines and tissues. Summarizing all
      data currently available, we conclude that the two cloned MCH receptors, MCH-R1
      and MCH-R2, exhibit differences in their expression pattern, although MCH-R1 is
      generally colocalized in all tissues where MCH-R2 expression is found. It appears
      that MCH-R1 is more abundant and has a wider distribution pattern than MCH-R2.
      Other hypothetical MCH-R subtypes may be expressed in specific tissues, e.g., in
      the pigment cell system.

PMID- 12503639
TI  - The BRET2/arrestin assay in stable recombinant cells: a platform to screen for
      compounds that interact with G protein-coupled receptors (GPCRS).
AB  - In BRET2 (Bioluminescence Resonance Energy Transfer), a Renilla luciferase (RLuc)
      is used as the donor protein, while a Green Fluorescent Protein (GFP2) is used as
      the acceptor protein. In the presence of the cell permeable substrate DeepBlueC,
      RLuc emits blue light at 395 nm. If the GFP2 is brought into close proximity to
      RLuc via a specific biomolecular interaction, the GFP2 will absorb the blue light
      energy and reemit green light at 510nm. BRET2 signals are therefore easily
      determined by measuring the ratio of green over blue light (510/395nm) using
      appropriate dual channel luminometry instruments (e.g., Fusion Universal
      Microplate Analyzer, Packard BioScience). Since no light source is required for
      BRET2 assays, the technology does not suffer from high fluorescent background or
      photobleaching, the common problems associated with standard FRET-based assays.
      Using BRET2, we developed a generic G Protein-Coupled Receptor (GPCR) assay based
      on the observation that activation of the majority of GPCRs by agonists leads to
      the interaction of beta-arrestin (a protein that is involved in receptor
      desensitization and sequestration) with the receptor. We established a cell line
      stably expressing the GFP2:beta-arrestin 2 fusion protein, and showed that it can
      be used to monitor the activation of various transiently expressed GPCRs, in
      BRET2/arrestin assays. In addition, using the HEK 293/GFP2:beta-arrestin 2 cell
      line as a recipient, we generated a double-stable line co-expressing the
      vasopressin 2 receptor (V2R) fused to RLuc (V2R:RLuc) and used it for the
      pharmacological characterization of compounds in BRET2/arrestin assays. This
      approach yields genuine pharmacology and supports the BRET2/arrestin assay as a
      tool that can be used with recombinant cell lines to characterize ligand-GPCR
      interactions which can be applied to ligand identification for orphan receptors.

PMID- 12503640
TI  - Bilateral demyelinating tumefactive lesions in three children with hemiparesis.
AB  - We present the results from the evaluations of three children ages of 2, 7, and
      11 years with hemiparesis and multiple white-matter lesions on magnetic resonance
      images (MRIs). The initial symptoms were mainly acute/subacute hemiparesis in all
      and headache/vomiting in one of them. Before admission, one of them had a history
      of upper respiratory tract infection, whereas another had undergone urinary tract
      surgery, and the other reported no history of any infection or stress-related
      factor. In all of the children, MRI showed multiple superficial and deep white
      matter hyperintensity in T2-weighted and proton density images with perifocal
      edema in the acute phase. During the symptomatic period, all of the patients
      underwent corticosteroid treatment. Whereas two of the patients demonstrated
      signs of recovery during the first week of treatment, the other patient
      demonstrated almost a full recovery with minimal neurologic sequela. Follow-up
      MRI demonstrated not only a remarkable decrease in the size and number of the
      lesions, with complete resolution for many of them, it also demonstrated a loss
      of contrast enhancement. None of these three patients, who had been followed up
      clinically and through MRI for 5 years, have shown either a clinical relapse or
      new lesions. The clinical pictures and MRI of the children were different in some
      aspects from acute multiple sclerosis and acute disseminated encephalomyelitis.
      Regarding both the clinical follow-up and treatment strategy, it is essential and
      interesting to state the fact that tumefactive lesions involving both hemispheres
      are likely to appear during the monitoring of the monophasic courses among
      inflammatory demyelinating diseases of childhood such as acute disseminated
      encephalomyelitis.

PMID- 12503641
TI  - Neuropsychologic effects of frontal lobe epilepsy in children.
AB  - Most published neuropsychologic studies on frontal lobe epilepsy have been
      performed on mixed groups of adults and adolescents with epilepsies of varying
      etiology. The cognitive profile of frontal lobe epilepsy in children has not been
      defined. The purpose of this study was to assess neuropsychologic performance in
      children with frontal lobe epilepsy. Intelligence and executive functions were
      examined in eight children (age 6 7/12 years to 13 11/12 years) with frontal lobe
      epilepsy. Performance was related to the focus side, seizure frequency, and age
      of epilepsy onset. Frontal lobe epilepsy was associated with a range of frontal
      dysfunctions, but IQ was generally spared. Left focus was associated with
      deficits in categorization, verbal long-term memory, and detailed visuospatial
      analysis. Frequent seizures correlated with attention difficulties and inability
      to inhibit impulsive responses. Children whose epilepsy appeared before age 6
      years had reduced ability to change behavioral strategies. Frontal epileptic
      activity alone can cause selective frontal deficits, the severity and nature of
      which are related to side, seizure frequency, and age of epilepsy onset. These
      findings require confirmation on larger series of selected children.

PMID- 12503642
TI  - Syntactic processing in Turner's syndrome.
AB  - A significant controversy concerning language development in Turner's syndrome
      has been found. Whereas some authors have observed that girls with Turner's
      syndrome maintain their verbal abilities intact, others have reported significant
      differences in Wechsler Verbal IQ when compared with normal controls. However,
      little has been studied about the linguistic characteristics of these patients
      when using tests to evaluate different linguistic levels. With the aim of
      assessing syntactic processes, 15 patients with Turner's syndrome (aged 8 to 19
      years) were compared with 15 healthy girls, matched by age, Wechsler Full-Scale
      IQ range, type of school (private or public), and school grade. A syntactic
      processing battery including 11 different subtests was developed. Compared with
      controls, the participants with Turner's syndrome obtained a fewer number of
      correct answers in most of the subtests and shorter latencies in some of them. We
      concluded that the subjects with Turner's syndrome have difficulties in using
      syntactic structures. It is suggested that some of these language difficulties
      are related to disturbances in using spatial-language relationships.

PMID- 12503643
TI  - Lipid peroxidation and antioxidative enzyme activities in childhood epilepsy.
AB  - This study aimed to investigate the relationship among lipid peroxidation,
      subsequent activation of scavenger enzymes (superoxide dismutase and glutathione
      peroxidase), and the presence of structural abnormality in 52 epileptic children
      receiving monotherapy (medically responsive) or polytherapy (medically
      intractable). Plasma lipid peroxidation in epileptic patients with abnormal
      magnetic resonance imaging (MRI) findings significantly increased as compared
      with that of 16 healthy children (P < .05), whereas antioxidant enzymes were not
      significantly affected. Both medically controlled and intractable children with
      normal MRI had higher activities of superoxide dismutase than those of controls
      (P < .05). The activity of superoxide dismutase in epileptic patients with
      structural abnormality did not significantly change as compared with controls.
      Activity of glutathione peroxidase in all of the epileptic children was not
      significantly different from controls. The activity of antioxidant enzymes or
      plasma malonyldialdehyde levels did not correlate with duration of epilepsy,
      frequency of seizures (> one seizure per month or not), and the presence or
      localization (focal, multifocal, or generalized) of electroencephalographic or
      MRI abnormalities. Increased plasma lipid peroxidation may be causally related to
      the presence of structural abnormality rather than ongoing epileptic activity or
      therapy status.

PMID- 12503644
TI  - Hemimegalencephaly in tuberous sclerosis complex.
AB  - The purpose of this case report is to describe the computed tomographic and
      magnetic resonance imaging findings of the brain of a 16-month-old girl with an
      uncommon association between hemimegalencephaly and tuberous sclerosis complex.
      When a large calcification is found within a hemimegalencephalic cerebral
      hemisphere, further investigation of a suspected associated tuberous sclerosis
      complex or another phakomatosis is required to determine pertinent treatment
      options and genetic counseling.

PMID- 12503645
TI  - Prospective long-term follow-up of patients with pervasive developmental
      disorders.
AB  - We conducted a 12-year prospective study of children with pervasive developmental
      disorders from North Dakota. In a prospective longitudinal follow-up study, of 59
      patients, we found 52 patients with pervasive developmental disorders (88%). Ten
      (17%) declined to participate. We collected data on 42 (71%) of the original
      cohort. Of the 42 subjects, 1 died (1.7%). The other 41 were followed up for 492
      person-years. Severity scores for the Diagnostic and Statistical Manual of Mental
      Disorders-III-Revised (DSM-III-R) declined 20% and for DSM-IV 23%. Global
      Assessment of Functioning improved 19%, and the average number of comorbidities
      decreased 45%. Thirty-seven percent of patients improved in all four measures,
      whereas only 5% improved in only one measure. Pervasive developmental disorders
      are developmental disorders with a long-term course of limited improvement for
      most patients. Male subjects demonstrated substantially more variability in
      improvement but, overall, demonstrated more improvement than female subjects.

PMID- 12503646
TI  - Epilepsy surgery in tuberous sclerosis: multistage procedures with bilateral or
      multilobar foci.
AB  - Refractory seizures are common in patients with tuberous sclerosis and can
      contribute to developmental delay and behavioral problems. Surgical intervention
      can reduce the seizure burden in selected patients with tuberous sclerosis and
      refractory epilepsy, thereby improving cognitive function, behavior, and quality
      of life. However, the risks of surgery are usually considered unacceptable when
      the epileptogenic focus lies over dominant hemisphere eloquent cortex or is
      multilobar. Multistage invasive monitoring can provide detailed data regarding
      the location and number of ictal foci and functional extraoperative mapping can
      precisely delineate the boundaries of eloquent areas of the brain. If independent
      ictal onsets are demonstrated, a staged surgical approach can allow a more
      aggressive yet safe procedure in selected patients. A combination of staged
      resection and multiple subpial transections may provide an opportunity to treat
      epileptogenic foci located over eloquent cortex. Bilateral staged resections can
      be used when independent bihemispheric foci are present in patients with tuberous
      sclerosis. This article presents two cases, one of which (case 2) was previously
      reported, on successful multistage surgical treatment of epileptogenic foci
      located over an eloquent cortex or in both hemispheres in children with tuberous
      sclerosis. This case is represented since there is additional follow-up available
      and the prior report was to a neurosurgical audience. This multistage approach
      permitted resection of epileptogenic foci that would traditionally have been
      considered inoperable.

PMID- 12503647
TI  - Clinical and macroscopic correlates of minicolumnar pathology in autism.
AB  - All subcortical arrangements are primarily nuclear in type. The cortex has been
      the first part of the brain to evolve a radial and laminar arrangement of cells.
      The resultant modular arrangement is based on the cell minicolumn: a self
      contained ecosystem of connectivity linking afferent, efferent, and inerneuronal
      connections. Recently, the cell minicolumn has been found to be abnormal in
      patients with autism. This article relates different aspects of the cell
      minicolumn and larger-scale neuronal assemblies to potential research techniques
      and their application to clinical practice.

PMID- 12503648
TI  - Benign familial infantile seizures: further delineation of the syndrome.
AB  - Benign familial infantile seizures are an autosomal dominant epilepsy disorder
      that is characterized by convulsions, with onset at age 3 to 12 months and a
      favorable outcome. Benign familial infantile seizures have been linked to
      chromosome 19q whereas infantile convulsions and choreoathetosis syndrome, in
      which benign familial infantile seizure is associated with paroxysmal
      choreoathetosis, has been linked to chromosome 16p 12-q12. Many additional
      families from diverse ethnic backgrounds have similar syndromes that have been
      linked to the chromosome 16 infantile convulsions and choreoathetosis syndrome
      region. Moreover, in one large pedigree with paroxysmal kinesiogenic dyskinesias
      only, the syndrome has also been linked to the same genomic area. Families with
      pure benign familial infantile seizures may be linked to chromosome 16 as well.
      In this study, we present a series of 19 families and 24 otherwise healthy
      infants with benign familial infantile seizures. Two of these families include
      members affected with benign familial infantile seizures and paroxysmal
      choreoathetosis. We included patients with normal neurologic examinations, who
      started having simple partial seizures, complex partial seizures, or apparently
      generalized seizures without recognized etiology between 2 months and 2 years of
      age. Neurologic studies were normal, but in all patients, there was a history of
      similar seizures and age at onset in either the father or the mother. Twenty-four
      patients (14 girls and 10 boys) were evaluated at our hospital between February
      1990 and February 2001. Age at onset, sex, family history of epilepsy and/or
      paroxysmal dyskinesias, neurologic examination, semiology, distribution, and
      frequency and duration of seizures were evaluated. Electroencephalographic (EEG)
      and neuroradiologic studies were also performed. Seizures began between 3 and 22
      months of life, with a median age of 5 1/2 months. Nine patients (37.5%) had only
      apparently generalized seizures, 5 patients (20.8%) had only partial seizures,
      and 10 patients had both partial and apparently generalized seizures (41.6%).
      Seizures were invariably brief, occurred during the waking state (100%), and
      presented mainly in clusters in 12 patients (50%). Interictal EEG was normal in
      23 patients (95.8%). Sixteen patients (66.6%) had a confirmed history of
      convulsions in family members other than parents. Twenty-two patients became
      seizure free after 30 months of life. Two brothers in the same family had brief
      paroxysmal episodes of choreoathetosis in the hemibody triggered by stress while
      awake at 15 and 17 years old, respectively. One of them had paroxysmal
      choreoathetosis only, and the other was associated with benign familial infantile
      seizures. One father had brief spontaneous episodes of paroxysmal choreoathetosis
      when awake at age 18 years. All of them had a good response to antiepilepsy
      drugs, and neurologic examination and EEG and neuroradiologic studies were
      normal. Benign familial infantile seizure is a genetic epilepsy syndrome with
      autosomal dominant inheritance. It may be associated with paroxysmal
      choreoathetosis (infantile convulsions and choreoathetosis syndrome), which has
      been linked to the chromosome 16 infantile convulsions and choreoathetosis
      syndrome region. Patients in families with infantile convulsions and
      choreoathetosis syndrome could display either benign familial infantile seizures
      or paroxysmal choreoathetosis or both. It is likely that the disease in families
      with pure benign familial infantile seizures may be linked to the infantile
      convulsions and choreoathetosis region as well. We cannot exclude the possibility
      that the youngest patients may develop choreoathetosis or other dyskinesias later
      in life.

PMID- 12503649
TI  - Rett syndrome phenotype following infantile acute encephalopathy.
AB  - Rett syndrome is a progressive neurodevelopmental disorder with a well-defined
      clinical spectrum and course. Recently, mutations in the gene encoding X-linked
      methyl-CpG binding protein 2 (MECP2) have been identified as the cause of Rett
      syndrome. Along with the classic form, variant forms of Rett syndrome and Rett
      syndrome phenotypes are also recognized. We report on a girl who, at age 2
      months, developed an acute encephalopathy with destructive brain damage 12 hours
      after acellular pertussis vaccination. Peripheral lymphocyte subset analysis
      revealed the existence of T lymphocytes double positive for CD4 and CD8 markers.
      This pattern normalized over the following 3 months. Months later, the girl
      manifested a Rett syndrome phenotype. DNA screening of the MECP2 gene was
      unrevealing in the child and her parents. This previously unreported association
      emphasizes the notion that Rett syndrome phenotypes can result from different
      (either genetic or environmental) causes.

PMID- 12503650
TI  - Treatment of subacute sclerosing panencephalitis with interferon-alpha,
      ribavirin, and inosiplex.
AB  - Subacute sclerosing panencephalitis is an almost universally fatal late
      complication of measles infection for which there is no established treatment. We
      report a patient with subacute sclerosing panencephalitis who was bed-bound and
      ataxic and had a left hemiparesis and frequent myoclonus. He was started on a new
      regimen consisting of intraventricular interferon-alpha (starting at 100,000
      U/m2/day, building up to 1 million U/m2/day), ribavirin (60 mg/kg/day
      intravenously), and inosiplex (3 g/day) and improved markedly. At 10 weeks, the
      intraventricular reservoir was removed because of bacterial infection, and he was
      discharged home on oral ribavirin (1200 mg/kg/day) and inosiplex. He continued to
      improve as judged by neurologic examination, functional independence measurement,
      neuropsychometry and single photon emission computed tomography (SPECT) imaging.
      However, after 10 months, he deteriorated suddenly and died before further
      intraventricular treatment could be instituted. Further trials are needed to
      evaluate long-term combination therapy in subacute sclerosing panencephalitis.

PMID- 12503651
TI  - Hemiconvulsion-hemiplegia syndrome and elevated interleukin-6: case report.
AB  - We report a 2-year-old boy who developed hemiconvulsion-hemiplegia syndrome with
      left-sided hemiplegia after a seizure lasting 35 minutes. The interleukin-6 level
      in the cerebrospinal fluid 2 hours after seizure onset was elevated to levels
      seen in patients with encephalitis. At 1 year after onset of the seizure, the
      patient remained hemiplegic on the left side, and magnetic resonance imaging
      showed severe right hemispheric atrophy. Acute changes seen on imaging studies
      and electroencephalograms in this patient were consistent with seizure-induced
      brain damage. Elevation of cerebrospinal fluid interleukin-6 may be related to
      the severe neurologic sequelae of our patient despite the relatively short
      seizure duration.

PMID- 12503652
TI  - Expression of adhesion and extracellular matrix molecules in the developing human
      brain.
AB  - Cell adhesion molecules and extracellular matrix molecules have important roles
      in cell migration and connection. Their developmental expression has not been
      fully described in humans. In this report, these molecules were examined by
      immunohistochemistry in frontal tissue samples from 14- to 28-week-old fetuses
      aborted for obstetric reasons (n = 20) and four fetuses with nervous system
      abnormalities. Neural cell adhesion molecule (NCAM), tenascin, and laminin were
      expressed after 17 weeks. Neural cell adhesion molecule was observed in the
      neuropil, whereas tenascin and laminin also had cellular and vascular expression.
      Thrombospondin and fibronectin, apparent after 14 weeks, showed a redistribution
      from periventricular to outer cortical layers after midgestation. N-cadherin and
      integrin were observed in mid- and late gestation. Maternal or environmental
      conditions seemed to influence the pattern of expression. Fetuses with nervous
      system abnormalities had altered expression of several molecules. The descriptive
      data obtained in this study might constitute a basis for further studies
      investigating the role of these molecules in developmental abnormalities of the
      brain.

PMID- 12503653
TI  - Association between factor V Leiden mutation and the hemiconvulsion, hemiplegia,
      and epilepsy syndrome: report of two cases.
AB  - The factor V Leiden mutation is the most common hereditary cause of venous
      thrombosis in our population. In the pediatric population, it has been associated
      with cerebrovascular thrombosis, cerebral palsy, and prosencephaly in neonates.
      We present two children with hemiconvulsion, hemiplegia, and epilepsy syndrome in
      whom the cause is likely attributable to the factor V Leiden mutation. We suggest
      that patients presenting with hemiconvulsion, hemiplegia, and epilepsy syndrome
      should be routinely investigated for factor V Leiden, and, if positive, careful
      consideration should be given to therapeutic and prophylactic anticoagulation as
      this may improve long-term outcome.

PMID- 12503654
TI  - Severe spinal muscular atrophy variant associated with congenital bone fractures.
AB  - Infantile autosomal recessive spinal muscular atrophy (type I) represents a
      lethal disorder leading to progressive symmetric muscular atrophy of limb and
      trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are
      caused by deletions or mutations in the survival motoneuron gene (SMNI) on
      chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with
      additional clinical features (respiratory distress, cerebellar hypoplasia) have
      been designated in the literature as infantile spinal muscular atrophy plus
      forms. In addition, the combination of severe spinal muscular atrophy and
      neurogenic arthrogryposis has been described. We present clinical, molecular, and
      autopsy findings of a newborn boy presenting with generalized muscular atrophy in
      combination with congenital bone fractures and extremely thin ribs but without
      contractures.

PMID- 12503655
TI  - Spinal muscular atrophy with congenital fractures: postmortem analysis.
AB  - We present a male infant with congenital fractures and features typical of spinal
      muscular atrophy. Mid-shaft fractures of the left humerus and both femurs
      occurred in utero. The patient died at 8 months of age following recurrent
      respiratory tract infections. His peripheral electrophysiologic studies were
      consistent with anterior horn cell disease. Molecular genetic studies were
      negative for the SMN gene. At autopsy, extensive anterior horn cell loss was
      present. There was extensive disease of skeletal muscle with relative sparing of
      the diaphragm. This patient represents a further case of this rare and fatal
      disease.

PMID- 12503656
TI  - Iron food supplement.
AB  - OBJECTIVE: To develop an iron rich supplement with locally available foods and to
      test its feasibility in school going children (7-9 Years) belonging to low income
      families. METHODS: From the upper primary school in Rajendranagar 7-9 year-old
      children were screened for hemoglobin (Hb) levels and 36 children having Hb
      levels below 11 g/dl were selected. Based on their Hb levels, age, and gender, 24
      children were grouped as experimental and the rest as control. A supplement food
      (laddoo) was developed using locally available foods like jaggery, processed rice
      flakes, graden cress seeds and amaranth seeds (45:40:10.5). In the experimental
      group, children were given one laddoo per day for a period of 60 days. Effect of
      supplement on Hb levels, height and weight was assessed. RESULT: Anthropometric
      parameters showed that 97% of these children were undernourished, majority (50%)
      were in grade II malnutrition followed by grade (25%) and grade II (22%). A
      significant increase in Hb levels was observed in both the boys and girls after
      30 days of supplementation only. The increase was comparatively more in the first
      30 days than the second 30 days. The overall increase in Hb levels was more in 7
      8 years than the 8-9 years age group. In majority of the subjects progression
      from one Hb level to the next higher level was observed. There was no significant
      improvement in their height and weight. CONCLUSION: The product developed
      contributed around 39-mg% iron. Thus its efficacy as an iron rich supplement in
      combating iron deficiency anemia is reflected in the results obtained.

PMID- 12503657
TI  - Acute iron ingestion.
AB  - OBJECTIVE: Intoxication is one of the most common causes of admissions to
      emergency department in pediatric age group. Incidence of iron poisoning
      gradually increased because of wide spread use of iron containing drugs. METHOD:
      In this report, we present five cases of iron ingestion who were admitted to our
      emergency department within a year. RESULT: Whole bowel irrigation in addition to
      gastric lavage with an iron dose of over 50 mg/kg as well as deferoxamine
      treatment for patients in whom clinical and laboratory indications are present.
      CONCLUSION: The prompt recognition and treatment of children with acute iron
      poisoning is the single and the most critical point for decreasing the morbidity
      and mortality associated with iron containing products.

PMID- 12503658
TI  - Sensorineural hearing loss following acute bacterial meningitis in non-neonates.
AB  - OBJECTIVE: Sensorineural hearing loss (SNHL) is an important sequelae of acute
      bacterial meningitis (ABM) in children. This study was undertaken to determine
      the incidence of SNHL following meningitis in non-neonates and its correlation
      with various factors. METHODS: Children between the ages of 1 month and 12 years
      with ABM admitted in a teaching hospital over a period of 18 months were
      enrolled. Detailed history was taken, clinical examination performed and
      cerebrospinal fluid analyzed at commencement of therapy, 48 hours later and at
      the end of treatment. On discharge brainstem evoked response audiometry (BERA)
      was recorded. Data were analyzed using appropriate statistical tests. RESULTS:
      Out of 32 children enrolled, 9 (28.1%) developed SNHL, bilateral in 21.9% and
      unilateral in 6.2%. Among hearing impaired subjects, 11.2% had mild while 44.4%
      each had moderate and profound hearing loss. Age, presence of vomiting, altered
      sensorium seizures and aminoglycoside usage were not significantly different in
      those with and without SNHL, but the total duration of fever was (p<0.05). There
      was significantly higher protein content and neutrophils in the second CSF sample
      of those with SNHL. CONCLUSION: There is a greater than 50% probability of the
      child developing SNHL if neutrophil percentage in the second CSF is 80% or more.
      Since the overall risk of SNHL is significant in children with meningitis, it is
      recommended that BERA be recorded in all, so that early intervention may be
      possible.

PMID- 12503659
TI  - The clinical risk index of babies (CRIB) score in India.
AB  - OBJECTIVE: To assess the usefulness of clinical risk index of babies (CRIB score)
      in predicting neonatal mortality in extremely preterm neonates, compared to birth
      weight and gestation. METHODS: 97 preterm neonates with gestational age less than
      31 weeks or birth weight less than or equal to 1500 g were enrolled for the
      prospective longitudinal study. Relevant neonatal data was recorded. Blood gas
      analysis results and the maximum and the minimum FiO2 required by babies in first
      12 hours of life were noted. Mortality was taken as death while the baby was in
      nursery. The prediction of mortality by birth weight, gestational age and CRIB
      score was done using the Logistic model, and expressed as area under the ROC
      curve. RESULTS: The area under the ROC curve for birth weight, gestational age
      and CRIB score was almost the same, the areas being 0.829, 0.819 and 0.823
      respectively. Hence CRIB score did not fare better than birth weight and
      gestational age in predicting neonatal mortality. CONCLUSION: The CRIB score did
      not improve on the ability of birth weight and gestational age to predict
      neonatal mortality in the study.

PMID- 12503660
TI  - Mediastinal enteric duplication cyst containing aberrant pancreas.
AB  - OBJECTIVE: The purpose of the study is to report a unique association of clinical
      and pathological findings in a neonate. Foregut enteric duplication cysts--rare
      developmental anomalies that are associated with midline vertebral fusion
      anomalies. METHODS: We had a neonate with foregut duplication cyst who presented
      at birth with respiratory distress. The child also had associated communicating
      hydrocephalus. The patient underwent excision of the duplication cyst along with
      a ventriculo-peritoneal shunt. RESULT: The excised specimen revealed a
      duplication cyst lined by aberrant pancreatic tissue. CONCLUSION: The present
      case demonstrates histologically the presence of both pancreatic and gastric
      tissue.

PMID- 12503661
TI  - Scholastic difficulties with behavioural problems.
AB  - OBJECTIVE: The study aimed at investigating behavioral problems in children with
      scholastic skill difficulties. METHOD: A sample of children (n=20) aged 5 to 8
      years with scholastic difficulties with those who did not have difficulties was
      being compared. RESULT: It has revealed the number of externalizing,
      internalizing and learning problems in children with scholastic difficulties.
      CONCLUSION: Need for management of behavioral problems along with re-mediation of
      scholastic difficulties is highlighted.

PMID- 12503662
TI  - CT and MRI in the diagnosis of tuberculosis.
AB  - The advent of CT and MRI imaging in the last two decades has redefined the
      approach and analysis of various diseases including tuberculosis. Tuberculosis
      afflicts hollow and solid viscera. Genitourinary, hepatobiliary and adrenal
      tuberculosis is uncommon in children. CT and MRI have however shown several
      advantages over conventional radiology and other imaging modalities in early
      diagnosis and follow-up of tuberculosis in different parts of the body.

PMID- 12503663
TI  - Management of opportunistic infections in pediatric HIV.
AB  - Human immunodeficiency virus (HIV) causes a chronic infection that leads to
      profound immunosuppression. A hallmark of this process is the depletion of CD4+
      lymphocytes, which predisposes the patient to develop a variety of opportunistic
      infections and certain neoplasms. The CD4+ lymphocyte count is the best validated
      predictor of the likelihood of developing opportunistic infections (OI).
      Susceptibility to OI increases as HIV induced immunosuppression becomes more
      severe. The management of HIV infection hence involves not only inhibiting viral
      replication using antiretroviral drugs, but also treating OI. This article
      focuses on the management of such commonly occurring OI in HIV infected patients.

PMID- 12503664
TI  - Trisomy 21 with XYY.
AB  - A case of double aneuploidy involving chromosome 21 and Y is reported in an eight
      month-old infant with developmental delay and failure to thrive. Patient had all
      classical phenotypical features of trisomy 21 except, absence of epicanthal
      folds. The diagnosis was confirmed by cytogenetic study performed on peripheral
      blood leucocyte culture using G-banding. Literature review revealed only 17 cases
      of XYY and trisomy 21 reported so far. No such case is reported in Indian
      literature. Relevant literature is reviewed and possible effects of trisomy 21 on
      XYY and that of XYY on trisomy 21 has been discussed. A routine chromosomal study
      even in patient with classical features of Down syndrome has been advocated.
      Interestingly, our patient also had left to right shunts at atrial and ductal
      level and tricuspid regurgitation. Given the rarity of the disorder and scanty
      published data the incidence, phenotype and recurrence risk are difficult to
      establish.

PMID- 12503665
TI  - Neonatal spinal cord injury.
AB  - Neonatal spinal cord injury (SCI) is well described in the literature, though its
      diagnosis is often delayed or missed in the neonatal period. We present a neonate
      who was referred with upper gastrointestinal bleed and a diagnosis of spinal cord
      injury was subsequently made clinically and confirmed radiologically.

PMID- 12503666
TI  - Hepatitis and hematuria in scarlet fever.
AB  - Scarlet fever is a common and usually benign course when treated properly.
      Hepatitis due to scarlet fever has been described mostly in adults. A 2 1/2-year
      old boy presented with scarlet fever and jaundice, hematuria and elevated liver
      enzymes.

PMID- 12503667
TI  - Hirschsprung's disease associated with Ondine's curse.
AB  - This is a case report of a very rare combination of congenital aganglionosis of
      the intestine (Hirschsprung's disease) and congenital central hypoventilation
      syndrome-CCHS- (Ondine's curse). The combination is also called Haddad syndrome.
      In about 50% of the cases of CCHS there is associated Hirschsprung's disease.
      There are only about 48 cases reported worldwide. The disease has a very high
      mortality especially in the settings of a developing country.

PMID- 12503668
TI  - Cyanotic child--can it be methaemoglobinemia?
AB  - Methaemoglobinemia is a rare condition and can give surprise in emergency setup.
      We have encountered one such case in emergency recently that presented with both
      peripheral and central cyanosis without cardio-respiratory compromise. The
      patient was confirmed to be suffering from methaemoglobinemia due to
      antimalarials that he had received before coming to the hospital. Cyanosis due to
      methaemoglobinemia in our patient was precipitated by concomitant glucose 6
      phosphate dehydrogenase (G6PD) deficiency. The patient was managed with
      conservative management and vitamin C administration.

PMID- 12503669
TI  - Anencephaly with placental attachment.
AB  - Anencephaly is a severe defect of development of the neuraxis that is
      incompatible with survival. This particular neural tube defect is characterised
      by the absence of large portions of the cranium. The peculiar feature in this
      baby is the abnormal attachment of the placenta to the site of the skull defect.

PMID- 12503670
TI  - Congenital airway abnormalities in neonates.
AB  - Airway malformations such as laryngeal atresia, tracheal agenesis and subglottic
      stenosis are rare and present at birth with significant respiratory distress with
      or without stridor. There may be an initial improvement on bag and mask
      ventilation. Repeated attempts at intubation are met with failure. The related
      embryology and clinical aspect of airway malformations have been discussed. The
      prognosis in tracheal agenesis is universally fatal but cases with laryngeal
      atresia and subglottic stenosis may be saved with prompt tracheostomy and later
      surgical reconstruction.

PMID- 12503671
TI  - Primary hydatid cyst of neck muscles.
AB  - Primary hydatid disease of muscle is very rare. This was encountered in the
      muscles of posterior triangle of the neck in a 12-year-old boy. Hydatid Cyst of
      neck was excised and was followed by albendazole for six weeks. Rarity of this
      disease in muscles warrants the need for this case report.

PMID- 12503672
TI  - Kleine-Levin syndrome and encephalitis.
AB  - Kleine-Levin Syndrome is characterized by hypersomnolence, hyperphagia and sexual
      disinhibition. The article reported a case of 10-year-old boy with a two-week
      history of altered sensorium, irrelevant talks, markedly increasing appetite and
      tendency to sleep most of the times. Immediately preceding to it the child had
      been an episode of enteric fever confirmed by the serological tests.

PMID- 12503673
TI  - Inflammatory myofibroblastic tumor.
AB  - Inflammatory myofibroblastic tumors are well described in lung and upper
      respiratory tract of young adults and children. Intra-abdominal forms of the
      disease are reported to occur most frequently in the liver, followed by stomach,
      bowel and spleen. A 13-year-old girl who had intermittent fever ranging from 99
      101 degrees F of three months period and significant weight loss was referred as
      a case of pyrexia of unknown origin. The patient was subjected to laparotomy. A
      solid mass was found arising from the mesentery, four feet from the iliocaecal
      junction and was adherent to the wall of ileum. The patient became afebrile after
      the removal of the mass and has gained weight and remained well during the ten
      months since discharge.

PMID- 12503674
TI  - Cutaneous bacillary angiomatosis.
AB  - Bacillary angiomatosis is characterized by unique vascular lesions caused by
      infection with a small Gram staining bacillus of the genus Bartonella. It usually
      occurs in immunocompromised persons but can also occur in immunocompetent
      persons. We report a case of cutaneous bacillary angiomatosis in a 5-year-old
      immunocompetent child. He had infected lesions on the lips, after an injury,
      which was followed by lesions over the knees, buttocks, near the ankles and the
      elbows. Diagnosis was proved on histology. The lesions cleared after
      administration of erythromycin for 3 months. It is well to be aware of this
      condition in the context of increasing prevalence of AIDS.

PMID- 12503675
TI  - Sepsis in the newborn.

PMID- 12503676
TI  - Cryptosporidium hominis n. sp. (Apicomplexa: Cryptosporidiidae) from Homo
      sapiens.
AB  - The structure and infectivity of the oocysts of a new species of Cryptosporidium
      from the feces of humans are described. Oocysts are structurally
      indistinguishable from those of Cryptosporidium parvum. Oocysts of the new
      species are passed fully sporulated, lack sporocysts. and measure 4.4-5.4 microm
      (mean = 4.86) x 4.4-5.9 microm (mean = 5.2 microm) with a length to width ratio
      1.0-1.09 (mean 1.07) (n = 100). Oocysts were not infectious for ARC Swiss mice,
      nude mice. Wistar rat pups, puppies, kittens or calves, but were infectious to
      neonatal gnotobiotic pigs. Pathogenicity studies in the gnotobiotic pig model
      revealed significant differences in parasite-associated lesion distribution (P =
      0.005 to P = 0.02) and intensity of infection (P = 0.04) between C. parvum and
      this newly described species from humans. In vitro cultivation studies have also
      revealed growth differences between the two species. Multi-locus analysis of
      numerous unlinked loci, including a preliminary sequence scan of the entire
      genome demonstrated this species to be distinct from C. parvum and also
      demonstrated a lack of recombination, providing further support for its species
      status. Based on biological and molecular data, this Cryptosporidium infecting
      the intestine of humans is proposed to be a new species Cryptosporidium hominis
      n. sp.

PMID- 12503677
TI  - Active transport of L-proline in Trypanosoma cruzi.
AB  - L-proline is the main energy source in insect vector stages of most
      trypanosomatids, including Trypanosoma cruzi epimastigotes. This is the first
      biochemical description of two active proline transporter systems in T. cruzi.
      Uptake of this amino acid occurred by a low affinity system B and a high affinity
      system A. System B consistently appeared more specific than System A when excess
      competing amino acids were used in transport inhibition assays. Furthermore, the
      high affinity system is 70% inhibited by L-tryptophan, but the low affinity
      system is not. Both systems were found to be insensitive to the intracellular
      proline concentration and D-proline did not inhibit L-proline uptake showing that
      both systems are stereospecific. Both systems were Na+ and K+ independant but
      dependant on energy since ATP depletion impairs L-proline uptake. The combined
      action of carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP) and
      oligomycin, and the dependence of activity on pH, further differentiated between
      the two systems leading to the conclusion that the high affinity system is a H+
      gradient-dependant transporter whereas the low affinity system depends directly
      on ATP.

PMID- 12503678
TI  - Simple, filter-based PCR detection of Thelohania solenopsae (Microspora) in fire
      ants (Solenopsis invicta).
AB  - Thelohania solenopsae is a microsporidian parasite that may serve as a biological
      control agent for the red imported fire ant, Solenopsis invicta. A rapid, filter
      based PCR amplification method detecting a portion of the small-subunit ribosomal
      RNA gene was developed to facilitate field studies detecting the parasite in fire
      ants. Processing ant homogenates with a commercially available membrane-based
      system, FTA Classic Card technology, compared favorably with traditional DNA
      extraction and PCR amplification methods. As few as 100 spores were detected. The
      FTA membrane system is a simple, extraction-free method for detecting T.
      solenopsae in fire ants, and allows for easy archival storage of DNA samples.

PMID- 12503679
TI  - Density and diversity of protozoa in some arid Australian soils.
AB  - This is the first extensive study of soil protozoa of arid lands. Twenty-six
      samples from litters, soils, termitaria, and a cyanobacterial crust, collected
      from central and south Australian arid lands, were analyzed for numbers and
      species of gymnamoebae, ciliates, and testacea. Amoebae ranged from 1,000-5,000/g
      of material, and were two orders of magnitude more abundant than ciliates. Both
      groups increased in abundance and species richness from bare soils through
      spinifex to mulga to chenopod vegetations. Testacea ranged 900-5,000/g with
      similar species richness throughout vegetations, but reached 11,900/g with a
      doubling of species in a refugium in Kings Canyon. The most prevalent species of
      amoebae, ciliates, and testacea were taxa associated with ephemeral and disturbed
      habitats (r-selection). The cyanobacterial crust might be considered a micro
      refugium because it contained a number of non-encysting protozoa, including
      Thecamoeba sp. and Nassula picta, feeding on cyanobacterial filaments. The
      numbers and species richness of protozoa under shrubs were greater than in bare
      soils, supporting the resource island hypothesis that desert plants create soil
      heterogeneity by localizing soil fertility under their canopies.

PMID- 12503680
TI  - An extracellular monoADP-ribosyl transferase activity in Entamoeba histolytica
      trophozoites.
AB  - Due to the important role of monoADP-ribosyl transferases in physiological and
      pathological events, we investigated whether the protozoan parasite Entamoeba
      histolytica had monoADP-ribosyl transferase activity. Reactions were initiated
      using ameba-free medium as the source of both enzyme and ADP-ribosylation
      substrate(s) and [32P]NAD+ as source of ADP-ribose. Proteins were analyzed by
      electrophoresis, and [32P]-labeled proteins were detected by autoradiography.
      Using the crude extracellular medium, a major labeled product of Mr 37.000 was
      observed. The yield of this product was reduced markedly using medium from
      Brefeldin A-treated trophozoites, indicating that the extracellular monoADP
      ribosyl transferase and/or its substrate depended on vesicular transport. The
      labeling of the 37-kDa substrate was dependent on reaction time, temperature, pH,
      and the ratio of unlabeled NAD+ to [32P]NAD+. After two purification steps,
      several new substrates were observed, perhaps due to their enrichment. The
      reaction measured ADP-ribosylation since [14C-carbonyl]NAD+ was not incorporated
      into ameba substrates and a 75-fold molar excess of ADP-ribose caused no
      detectable inhibition of the monoADP-ribosyl transferase reaction. On the basis
      of sensitivity to NH2OH, the extracellular monoADP-ribosyl transferase of E.
      histolytica may be an arginine-specific enzyme. These results demonstrate the
      existence in E. histolytica of at least one extracellular monoADP-ribosyl
      transferase, whose localization depends upon a secretion process.

PMID- 12503681
TI  - Phylogenetic position of Licnophora, Lechriopyla, and Schizocaryum, three unusual
      ciliates (phylum Ciliophora) endosymbiotic in echinoderms (phylum Echinodermata).
AB  - Various echinoderms are colonized by species from several classes of the Phylum
      Ciliophora, indicating that the echinoderm "habitat" has been invaded
      independently on numerous occasions throughout evolutionary history. Two
      "echinoderm" ciliates whose phylogenetic positions have been problematic are
      Licnophora macfarlandi Stevens, 1901 and Schizocaryum dogieli Poljansky and
      Golikova, 1957. Licnophora macfarlandi is an endosymbiont of the respiratory
      trees of holothuroids, and S. dogieli is found in the esophagus of echinoids. A
      third species, Lechriopyla mystax Lynch, 1930, is a plagiopylid ciliate found in
      the intestine of echinoids. Host echinoderms were collected near the Friday
      Harbor Laboratories, San Juan Island, WA. Specimens of S. dogieli and L. mystax
      were obtained from the esophagus and intestine, respectively, of the sea urchin
      Strongylocentrotus pallidus. Specimens of L. macfarlandi were collected from the
      fluid obtained from the respiratory trees of Parastichopus californicus. Using
      small subunit ribosomal RNA (SSrRNA) sequences of these three ciliates and a
      global alignment of SSrRNA sequences of other ciliates, we established the
      following. 1) Licnophora is a spirotrich ciliate, clearly related to the
      hypotrichs and stichotrichs; this is corroborated by its possession of
      macronuclear replication bands. 2) Lechriopyla is the sister genus to Plagiopyla
      and is a member of the Class Plagiopylea, which was predicted based on its
      cytology. 3) Schizocaryum clusters in the Class Oligohymenophorea and is most
      closely related to the scuticociliates; there are currently no morphological
      features known to relate Schizocaryum to the scuticociliates.

PMID- 12503682
TI  - Multiple strains of the parasitic dinoflagellate Amoebophrya exist in Chesapeake
      Bay.
AB  - Small subunit rRNA sequences were amplified from Amoebophrya strains infecting
      Karlodinium micrum, Gymnodinium instriatum and an unidentified Scrippsiella
      species in Chesapeake Bay. The alignable parts of the sequences differed from
      each other and from the previously reported rRNA sequence of the Amoebophrya
      strain infecting Akashiwo sanguinea in Chesapeake Bay by 4 to 10%. This is a
      greater degree of difference than sometimes found between sequences from separate
      genera of free-living dinoflagellates. These sequence differences indicate that
      the Amoebophrya strains parasitizing dinoflagellates in Chesapeake Bay do not all
      belong to the same species. In spite of their relative dissimilarity, the
      sequences do group together into a single clade with high bootstrap support in
      phylogenetic trees constructed from the sequences.

PMID- 12503683
TI  - Induction of anti-actin drug resistance in Tetrahymena.
AB  - Both cytochalasin D and latrunculin B reversibly inhibited Tetrahymena
      phagocytosis at concentrations similar to those effective in mammalian systems,
      even though ciliate actins are known to be highly divergent from mammalian
      actins. Overnight exposure to relatively low (0.25 microM) concentrations of
      latrunculin B induced resistance in Tetrahymena to the inhibitory effects of that
      drug, as well as cross-resistance to cytochalasin D. However, much higher (> 30
      microM) concentrations of cytochalasin D were required for induction of cross
      resistance to latrunculin B. Anti-actin drug resistance in Tetrahymena may
      involve a general multidrug resistance mechanism and/or specific feedback
      regulation of F-actin assembly and stability.

PMID- 12503684
TI  - Identification and phylogenetic analysis of morphologically similar naked amoebae
      using small subunit ribosomal RNA.
AB  - Fan-shaped, naked amoebae are commonly encountered in samples from freshwater and
      marine habitats suggesting that they are an important component of the microbial
      food web. However, there are considerable problems in both detecting these
      amoebae and identifying them, given their morphological similarity. In this study
      we used restriction analysis and partial sequence analysis of the small-subunit
      18S ribosomal RNA gene to examine the phylogenetic relationships between nine
      "fan-shaped" Vannella and Platyamoeba species. The molecular phylogeny showed
      that the marine Vannella and Platyamoeba isolates are closely related, whereas
      the freshwater isolates are disparate. Thus, the current reliance on the fine
      structure of the cell coat (glycocalyx) used to separate these genera is not
      justified. The study also highlights sequence elements that might be targeted by
      fluorescent probes for the direct detection of these amoebae in field samples.
      The molecular data were also used to aid the identification of three unknown fan
      shaped isolates. All three unknowns resembled Vannella or Platyamoeba. However,
      one of the strains (a small < 10 microm, benthic, fan-shaped amoeba) probably
      represents a new genus.

PMID- 12503685
TI  - Myxobolus desaequalis n. sp. (Myxozoa, Myxosporea), parasite of the Amazonian
      freshwater fish, Apteronotus albifrons (Teleostei, Apteronotidae).
AB  - Myxobolus desaequalis n. sp. is described from the gill lamellae of the
      freshwater fish Apteronotus albifrons, collected in the Amazon River, near the
      city of Salvaterra, Brazil. Large spherical plasmodia filled with disporic
      pansporoblasts and spores were observed. Ellipsoidal to pyriform spores are 18.3
      microm length x 11.2 microm width x 4.4 microm thickness. The anterior end of the
      spores contain two extremely unequal pyriform polar capsules measuring: (larger):
      11.2 microm length, 4.9 microm width, and an isofilar polar filament with 11 to
      12 turns obliquely to the longitudinal axis; (smaller): 4.6 microm length, 2.8
      microm width, and an isofilar polar filament with 4 to 5 turns, obliquely to the
      longitudinal axis.

PMID- 12503686
TI  - Azadirachtin disrupts formation of organised microtubule arrays during
      microgametogenesis of Plasmodium berghei.
AB  - Transmission of malaria parasites from vertebrate blood to the mosquito vector
      depends critically on the differentiation of the gametocytes into gametes. This
      occurs in response to environmental stimuli encountered by the parasite in the
      mosquito bloodmeal. Male gametogenesis involves three rounds of DNA replication
      and endomitosis, and the assembly de novo of 8 motile axonemes. Azadirachtin, a
      plant limnoid and insecticide with an unkown mode of action, specifically
      inhibits the release of motile gametes from activated microgametocytes but does
      not inhibit growth and replication of a sexual blood stages. We have combined
      confocal laser scanning microscopy and transmission electron microscopy to
      examine the effect of azadirachtin on the complex reorganisation of the
      microtubule cytoskeleton during gametogenesis in Plasmodium berghei. Neither the
      replication of the genome nor the ability of tubulin monomers to assemble into
      microtubules upon gametocyte activation were prevented by azadirachtin. However,
      the drug interfered with the formation of mitotic spindles and with the assembly
      of microtubules into typical axonemes. Our observations suggest that azadarachtin
      specifically disrupts the patterning of microtubules into more complex
      structures, such as mitotic spindles and axonemes.

PMID- 12503687
TI  - The phylogeny of colpodellids (Alveolata) using small subunit rRNA gene sequences
      suggests they are the free-living sister group to apicomplexans.
AB  - In an attempt to reconstruct early alveolate evolution, we have examined the
      phylogenetic position of colpodellids by analyzing small subunit rDNA sequences
      from Colpodella pontica Myl'nikov 2000 and Colpodella sp. (American Type Culture
      Collection 50594). All phylogenetic analyses grouped the colpodellid sequences
      together with strong support and placed them strongly within the Alveolata. Most
      analyses showed colpodellids as the sister group to an apicomplexan clade, albeit
      with weak support. Sequences from two perkinsids, Perkinsus and Parvilucifera,
      clustered together and consistently branched as the sister group to
      dinoflagellates as shown previously. These data demonstrate that colpodellids and
      perkinsids are plesiomorphically similar in morphology and help provide a
      phylogenetic framework for inferring the combination of character states present
      in the last common ancestor of dinoflagellates and apicomplexans. We can infer
      that this ancestor was probably a myzocytotic predator with two heterodynamic
      flagella, micropores, trichocysts, rhoptries, micronemes, a polar ring, and a
      coiled open-sided conoid. This ancestor also very likely contained a plastid, but
      it is presently not certain whether it was photosynthetic, and it is not clear
      whether extant perkinsids or colpodellids have retained the organelle.

PMID- 12503688
TI  - Is sputum eosinophilia a good or poor predictor of benefit from inhaled
      corticosteroid therapy in asthma?

PMID- 12503689
TI  - European training of paediatricians to paediatric pulmonologists.

PMID- 12503690
TI  - Assessment and evaluation of symptomatic steroid-naive asthmatics without sputum
      eosinophilia and their response to inhaled corticosteroids.
AB  - Eosinophilic airway inflammation is one of the hallmarks of asthma. Sputum
      eosinophilia has been suggested as a predictor of the response to inhaled
      corticosteroids in asthma. This study sought to investigate the proportion of
      steroid-naive uncontrolled asthmatics without significant sputum eosinophilia (<
      or = 1%) and to examine whether sputum eosinophilia could predict the response to
      inhaled corticosteroids. A total of 51 mild uncontrolled steroid-naive asthmatics
      who had not been treated with oral or inhaled corticosteroids for at least 3
      months were investigated. The evaluation included a spirometry, methacholine
      inhalation challenge and sputum induction on two occasions, one at baseline and
      the other after 1 month of treatment with 250 microg twice-daily fluticasone
      propionate. Of the 51 subjects, 15 had an eosinophil count < or = 1%, and 46
      completed the two visits. Patients with baseline sputum eosinophils < or = 1%
      (n=14) were compared with those with sputum eosinophils > 1% (n=32). The baseline
      characteristics of these two groups were similar. After 1 month of treatment,
      respiratory symptoms, quality of life, forced expiratory volume in one second
      (FEV1) and provocative concentration causing a 20% fall in FEV1 improved in both
      groups. The absence of sputum eosinophilia does not seem to be an indicator of
      poor response to inhaled corticosteroid treatment in steroid-naive asthmatics.
      However, this finding needs to be investigated further in a double-blind, placebo
      controlled study, entirely designed to answer this question.

PMID- 12503691
TI  - Eosinophilic inflammation in sputum of poorly controlled asthmatics.
AB  - Despite full effective treatment, asthmatic patients often present with poorly
      controlled asthma. Airway eosinophilia is associated with asthma, but its
      relationship with asthma control is still undetermined. To investigate the
      relationship between airway eosinophilia and asthma control, cellular and
      biochemical markers of airway inflammation were measured in 19 subjects with
      poorly controlled asthma, 16 subjects with asthma under control and eight normal
      volunteers. The severity of asthma was mild-to-moderate persistent in 23 patients
      (14 poorly controlled) and severe prednisone-dependent in 12 subjects (five
      poorly controlled). Induced sputum was analysed for total and differential cell
      counts, leukotriene E4 (LTE4), eosinophil cationic protein (ECP), regulated on
      activation, normal T-cell expressed and secreted (RANTES), and interleukin (IL)
      8. Sputum eosinophils, LTE4, ECP and RANTES levels (but not IL-8) were
      significantly higher in patients with poorly controlled asthma as compared to
      patients with controlled asthma. By contrast, sputum cells and sputum
      inflammatory markers were not different among groups of patients with different
      severity of asthma. These results suggest that sputum eosinophilia is associated
      with poorly controlled asthma rather than with the severity of asthma.

PMID- 12503692
TI  - Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled
      study.
AB  - Although the anti-inflammatory effects of inhaled corticosteroids in the
      treatment of asthma are established, the effects of long-acting beta2-adrenergic
      receptor agonists on inflammation are the subject of debate. The aim of the
      present study was to determine the effect of salmeterol on the numbers of
      inflammatory cells in biopsy samples of distinct immunophenotype and those
      expressing the genes for interleukin-4 and -5, regulatory cytokines particularly
      relevant to asthma. Twenty patients (aged 18-55 yrs) with mild stable asthma were
      randomised in a three-way crossover study to 6 weeks of treatment with: 1)
      salmeterol (50 microg b.d.; SM50); 2) fluticasone propionate (250 microg b.d.;
      FP250), or 3) placebo. Compared with placebo, SM50 significantly reduced the
      numbers of neutrophils in bronchial biopsy samples and the concentrations of
      myeloperoxidase and soluble E-selectin in serum, each of which reflect neutrophil
      involvement. Compared with FP250, SM50 reduced neutrophil number and human
      neutrophil lipocalin level in bronchial lavage fluid and intercellular adhesion
      molecule-1 level in bronchoalveolar lavage fluid. Compared with placebo, FP250
      significantly reduced the numbers of (CD3+) T-lymphocytes, (CD4+) T-helper cells,
      (CD45RO+) activated T-helper cells and eosinophils in the biopsy samples; it also
      reduced the percentage of eosinophils and soluble intercellular adhesion molecule
      1 in serum. The percentage of symptom-free days and nights and airways
      hyperresponsiveness improved significantly after SM50 compared to both placebo
      and FP250. In conclusion, a novel antineutrophilic effect of the inhaled long
      acting beta2-adrenergic receptor agonist, salmeterol, in mild asthma is reported.

PMID- 12503693
TI  - Mometasone furoate is a less specific glucocorticoid than fluticasone propionate.
AB  - Fluticasone propionate (FP) and mometasone furoate (MF) are potent synthetic
      corticosteroids that are widely used as anti-inflammatory agents to treat
      respiratory diseases. As part of the assessment of the potential for side-effects
      associated with their use, their activities, not only at the glucocorticoid
      receptor (GR) but also at the other members of the steroid nuclear receptor
      family, have been compared. Cell-based functional systems were established to
      measure different aspects of GR function, as well as the activity at all the
      other steroid nuclear receptors. The effects of MF and FP on the GR were potent
      and indistinguishable. Neither corticosteroid showed any activity at the
      oestrogen receptor, while both were weak antagonists of the androgen receptor. FP
      was a relatively weak agonist of the progesterone receptor but MF was a very
      potent agonist of the progesterone receptor, giving activity at similar
      concentrations to those that stimulate the GR (concentration generating 50%
      maximal effect (EC50)=50 pM). Moreover, while FP was a weak antagonist of the
      mineralocorticoid receptor (concentration generating 50% maximal inhibitory
      effect=80 nM), MF displayed potent partial agonist activity (EC50=3 nM, 30%).
      Mometasone furoate is considerably less specific for the glucocorticoid receptor
      than fluticasone propionate, showing significant activity at other nuclear
      steroid receptors.

PMID- 12503694
TI  - Adenosine in exhaled breath condensate in healthy volunteers and in patients with
      asthma.
AB  - Persistent airway inflammation may require the use of different markers for
      monitoring airway inflammation. In this study, the authors investigated whether
      adenosine, which may be produced in allergic inflammatory conditions, could be
      measured with good reproducibility in exhaled breath condensate (EBC), and
      whether its concentration was elevated in patients with asthma. EBC adenosine and
      exhaled nitric oxide (eNO), a noninvasive marker of asthmatic airway
      inflammation, were measured in 40 healthy volunteers and 43 patients with
      allergic bronchial asthma. Repeatability of adenosine measurement was checked in
      20 pairs of samples collected from healthy control subjects. Adenosine was
      detectable in all EBC samples by the applied high-performance liquid
      chromatographic method. The mean difference between repeated measurements of
      adenosine was -0.1 nM and all differences were within the coefficient of
      repeatability. Adenosine concentration was higher in steroid-naive patients
      (n=23) compared with healthy control subjects and steroid-treated patients
      (n=20). In patients with worsening symptoms of asthma (n=23), adenosine
      concentration was elevated compared with those in a stable condition (n=20).
      Furthermore, adenosine concentrations were related to eNO levels in asthmatic
      patients. These results, showing good reproducibility of adenosine measurements
      and increased adenosine concentrations in steroid-naive patients and in patients
      with worsening of asthmatic symptoms, indicate that adenosine measurement in
      exhaled breath condensate might be an acceptable novel method to investigate the
      role of local production of adenosine in the airways.

PMID- 12503695
TI  - Diaphragmatic function after intense exercise in congestive heart failure
      patients.
AB  - Respiratory muscle strength and endurance is reduced in patients with congestive
      heart failure, making these patients susceptible to diaphragmatic fatigue during
      exercise. In order to determine whether or not contractile fatigue of the
      diaphragm occurs in patients with congestive heart failure following intense
      exercise, twitch transdiaphragmatic pressures (twitch Ptdi) were measured during
      unpotentiated and potentiated cervical magnetic stimulation (CMS) of the phrenic
      nerves before and at intervals after cycle endurance exercise. Ten patients aged
      65.7+/-6.0 yrs (mean+/-SD) with an ejection fraction of 31.2+/-9.8% performed a
      constant-load symptom-limited exercise test at 60% of their peak work capacity.
      Twitch Ptdi at baseline were 15.9+/-6.3 cmH2O (unpotentiated CMS) and 28.8+/-10.7
      cmH2O (potentiated CMS) and at 10 min postexercise were 16.4+/-4.7 cmH2O
      (unpotentiated CMS) and 27.6+/-10.1 cmH2O (potentiated CMS). One patient
      demonstrated a sustained fall in twitch Ptdi of > or = 15%, considered
      potentially indicative of diaphragmatic fatigue. Contractile diaphragmatic
      fatigue is uncommon in untrained patients with congestive heart failure following
      high-intensity constant-workload cycle exercise. Therefore, diaphragmatic fatigue
      is an unlikely cause of exercise-limitation during activities of daily living in
      heart failure patients.

PMID- 12503696
TI  - Copenhagen City Heart Study: longitudinal analysis of ventilatory capacity in
      diabetic and nondiabetic adults.
AB  - The natural history of lung function in diabetes is unknown due to the lack of
      longitudinal observations. The decline of forced expiratory volume in one second
      (FEV1) and forced vital capacity (FVC) was studied over 15 yrs in the 17,506
      adult participants of The Copenhagen City Heart Study, which included 266
      individuals with diabetes. Multiple linear regression and a mixed-effects model
      were used, taking into account correlation between repeated measurements and
      adjusting for relevant confounders. In both sexes, FEV1 and FVC were consistently
      lower in diabetic individuals, compared with healthy individuals, with an average
      reduction of approximately 8% of the predicted value. Longitudinal analyses
      showed that the decline of FEV1 and FVC in diabetic individuals was similar to
      that observed in nondiabetic subjects. It was concluded that although diabetic
      subjects have, on average, a lower forced expiratory volume in one second and
      forced vital capacity than individuals without diabetes, this deficit seems not
      to be progressive in the long term. These observations may be of importance with
      regard to diabetes treatment with inhaled pulmonary insulin, which is likely to
      become available within a few years.

PMID- 12503697
TI  - Effect of medroxyprogesterone on arterial blood gases, leptin and neuropeptide Y
      in postmenopausal females.
AB  - Natural progesterone, a potent respiratory stimulant, stimulates leptin
      production in premenopausal females. Leptin and its counterpart neuropeptide Y
      (NPY) have recently been linked with respiration. The effect of
      medroxyprogesterone acetate (MPA) on arterial blood gases, serum leptin and NPY
      was evaluated in this study. Fourteen postmenopausal females with respiratory
      impairment, due mostly to chronic obstructive pulmonary disease, were recruited
      for a randomised, double-blind, placebo-controlled crossover trial. Arterial
      blood gases, serum leptin and NPY concentrations were measured at baseline and
      after 14 days of treatment with placebo and MPA, separated by a 6-week washout
      period. Thirteen patients completed the trial. The mean+/-SD carbon dioxide
      tension in arterial blood (Pa,CO2) was 5.4+/-0.6 kPa at baseline, and decreased
      by 0.8+/-0.3 kPa during treatment with MPA. The oxygen tension in arterial blood
      (Pa,O2) and pH did not change. At baseline, the mean base excess was 0.6+/-1.9
      mmol x L(-1) and the mean bicarbonate (HCO3-) concentration was 25.1+/-1.6 mmol x
      L(-1). With MPA, base excess decreased by 2.2+/-1.2 mmol x L(-1) and HCO3- by
      1.9+/-1.0 mmol x L(-1) from baseline. The mean concentrations of serum leptin
      (19.8+/-9.9 microg x L(-1) at baseline, 19.7+/-9.8 microg x L(-1) with MPA) or
      NPY (94.0+/-18.3 pmol x L(-1) at baseline, 85.1+/-41.2 pmol x L(-1) with MPA) did
      not change. However, the reduction in Pa,CO2 correlated with the reduction of
      serum leptin concentration. Medroxyprogesterone acetate effectively decreased the
      carbon dioxide tension in postmenopausal females with chronic respiratory
      impairment. The results suggest that a decrease in the carbon dioxide tension of
      > or = 0.9 kPa is necessary for a reduction in serum leptin concentration.

PMID- 12503698
TI  - Size matching in lung transplantation using predicted total lung capacity.
AB  - Height is used in allocation of donor lungs as an indirect estimate of thoracic
      size. Total lung capacity (TLC), determined by both height and sex, could be a
      more accurate functional estimation of thoracic size. Size-matching criteria
      based on height versus predicted TLC was retrospectively evaluated, and,
      furthermore, whether a TLC mismatch was related to clinical and functional
      complications. The ratio of donor and recipient height, as well as the ratio of
      predicted TLC in donors and recipients, were calculated in 80 patients after
      bilateral lung transplantation. Complications evaluated included persistent
      atelectasis, persistent pneumothorax and increased number of days in intensive
      care, occurrence of bronchiolitis obliterans syndrome and limitation of exercise
      capacity. Median height donor/recipient ratio was 1.01 (0.93-1.12). Median
      predicted TLC donor/recipient ratio was 1.01 (with a clearly broader range 0.72
      1.41). Neither sex mismatch nor TLC mismatch were related to clinical or
      functional complications. Allocation of donor lungs based upon height alone leads
      to a substantial mismatch in total lung capacity caused by sex mismatch. The
      absence of complications suggests that a greater height donor/recipient
      discrepancy can be accepted for allocation than previously assumed.

PMID- 12503699
TI  - Effects of terbutaline in combination with mannitol on mucociliary clearance.
AB  - Beta2-agonists and osmotic agents stimulate mucociliary clearance (MCC) via
      different mechanisms which could potentially interact. The effects of inhaling
      terbutaline in combination with mannitol on MCC were investigated in nine healthy
      (aged 19+/-1 yrs) and 11 mild (aged 21+/-4 yrs) asthmatic subjects. Using 99mTc
      sulphur colloid radioaerosol and a gamma camera, MCC was studied on four separate
      days with each of the following interventions: 1) terbutaline or its placebo
      inhaled 10 min before mannitol (in random, double blind); 2) terbutaline inhaled
      5 min after mannitol; and 3) terbutaline inhaled 10 min before the control for
      mannitol. Lung images were collected over a period of 120 min postintervention
      and over 150 min in total. The mannitol-induced increase in clearance was
      transiently inhibited by terbutaline pretreatment and transiently enhanced when
      terbutaline was administered after mannitol both in asthmatic and healthy
      subjects. The order of administration of mannitol and terbutaline did not affect
      the total clearance of radioactive mucus over 140 min from the start of
      intervention in both groups. The pathways through which terbutaline and mannitol
      increase mucociliary clearance may transiently interact in an inhibitory or
      synergistic way, depending on the order of administration. However, this did not
      affect the overall increase in mucociliary clearance over 140 min.

PMID- 12503700
TI  - Regulation of E-cadherin expression by dexamethasone and tumour necrosis factor
      alpha in nasal epithelium.
AB  - Asthma and rhinitis often coexist and share many clinical features. The extent of
      epithelial alteration in nasal inflammation is controversial. Cell-cell adhesion
      plays an important role in tissue morphogenesis and homeostasis and is mediated
      by the cadherin family. In human bronchial epithelial cells the authors have
      shown that tumour necrosis factor (TNF)-alpha induced a significant decrease of E
      cadherin and beta-catenin expression. The addition of dexamethasone inhibited
      this decrease. The aim of the present study was to investigate the effect of TNF
      alpha and dexamethasone on the regulation of E-cadherin, gamma-catenin and beta
      catenin in human nasal epithelial cells (HNEC). A primary culture of HNEC,
      obtained from human nasal turbinates after surgery, was used. The quantitative
      and qualitative modulation of E-cadherin, gamma-catenin and beta-catenin
      expression was assessed by Western blot and immunofluorescence analysis. In order
      to assess the TNF-alpha-induced activation of HNEC, interleukin-8 and RANTES
      (regulated on activation, normal T-cell expressed and secreted) release was
      assessed by enzyme-linked immunosorbent assay. The results showed that TNF-alpha
      induced, a decrease in gamma-catenin and beta-catenin expression, but had no
      effect on E-cadherin expression. Immunofluorescence showed that TNF-alpha induced
      cytoplasmic localisation of E-cadherin, gamma-catenin and beta-catenin.
      Dexamethasone inhibited the effect of TNF-alpha and induced a three-fold increase
      in E-cadherin expression. These results suggest that the difference in nasal and
      bronchial epithelial cohesion may be due to the differential effect of tumour
      necrosis factor-alpha and dexamethasone on E-cadherin expression.

PMID- 12503701
TI  - Applicability of laser scanning cytometry to study paediatric alveolar
      macrophages.
AB  - Laser scanning cytometry (LSC) generates quantitative information on immune
      receptor expression from cells cytocentrifuged onto a microscope slide. In
      children, the description of developmental changes in immune receptor expression
      on alveolar macrophages (AM) has been limited by the small number of cells
      recovered by bronchoalveolar lavage (BAL). The applicability of LSC to the study
      of AM from normal children was therefore assessed. AM were obtained by BAL of
      normal children following intubation prior to elective surgery. The ability of
      LSC to identify the cytoplasm of AM was assessed using either: 1)
      autofluorescence; 2) forward scatter; 3) nuclear staining with propidium iodide;
      or 4) a fluorescent-labelled monoclonal antibody to CD68, a pan-macrophage
      antigen. LSC could only reliably identify individual AM when stained with CD68.
      The sensitivity for detecting single whole AM using CD68 was 0.97 and the
      positive predictive value was 0.88, respectively, with excellent repeatability.
      In addition, a range of immunofluorescence parameters were generated for CD68. It
      is concluded that laser scanning cytometry is suited to the study of immune
      receptor expression from small numbers of paediatric alveolar macrophages, when
      CD68 is used for cell identification.

PMID- 12503702
TI  - Hypertonic saline increases tight junction permeability in airway epithelium.
AB  - Asthmatics are known to react to inhaled hyperosmolar solution. Therefore, the
      effect of hyperosmolar salt solutions on tight junctions of the airway epithelium
      was investigated by electron microscopy. Rat trachea was perfused with different
      concentrations of sodium chloride (NaCl) and then fixed from the luminal side
      with glutaraldehyde to which the electron dense tracer lanthanum chloride had
      been added. Lanthanum penetrated 3+/-1% of the tight junctions in trachea
      perfused with 295 mOsm Krebs-Ringer's buffer (KRB). Adding NaCl to the KRB (KRB
      NaCl) increased osmolarity of the solution. After perfusion with 589 or 876 mOsm
      KRB-NaCl, lanthanum was observed in the lateral intercellular spaces in 50+/-11
      and 57+/-6%, respectively. The effect of hyperosmolarity was reversible and only
      6+/-1% of the tight junctions were penetrated after perfusion with 295 mOsm KRB
      solution following 589 mOsm KRB-NaCl perfusion. Adding mannitol to the KRB to an
      osmolarity of 589 mOsm only caused 5+/-1% of the tight junctions to open, even
      though osmotic effects were observed. Opening the tight junctions with
      hyperosmolar salt solutions may play a role in exercise-induced asthma. It may
      also open the prospect for increased penetration of inhaled drugs into the
      interstitium and the circulation.

PMID- 12503703
TI  - Vascular endothelial growth factor mRNA and protein expression in airway
      epithelial cell lines in vitro.
AB  - Vascular endothelial growth factor (VEGF) plays multifunctional roles in vascular
      permeability, repair and remodelling processes, in addition to the maintenance of
      vascular structure and function. In the present study, the potential of airway
      epithelial cell lines, BEAS-2B cells and A549 cells, to release and express VEGF
      in unstimulated and stimulated conditions was evaluated. The secretion and
      expression of VEGF were evaluated by enzyme-linked immunosorbant assay and by
      reverse transcriptase-polymerase chain reaction. The isoforms of released VEGF
      were determined by high-performance liquid chromatography. BEAS-2B cells and A549
      cells released VEGF constitutively. Interleukin (IL)-1beta and tumour necrosis
      factor (TNF)-alpha augmented the release of VEGF in a time- and dose-dependent
      manner. The released VEGF was 165 amino acid residues in either condition.
      Pseudomonas aeruginosa lipopolysaccharide (LPS), interferon (IFN)-gamma, smoke
      extract (SE), neutrophil elastase (NE), and bradykinin stimulated the release of
      VEGF. Keracinocyte growth factor (KGF), which reduces vascular permeability, also
      stimulated both cells to release VEGF. VEGF messenger ribonucleic acid (mRNA) was
      expressed both time- and dose-dependently at 2 h, and declined after 2 h in
      response to IL-1beta and TNF-alpha. The expression of VEGF mRNA in airway
      epithelial cells was also augmented by LPS, IFN-gamma, SE, NE, and KGF
      stimulation. These data suggest that airway epithelial cells may regulate the
      maintenance of vascular structure and function, as well as vascular permeability,
      repair and remodelling processes, in a variety of lung conditions by expressing
      vascular endothelial growth factor.

PMID- 12503704
TI  - Sequential genotyping of Pseudomonas aeruginosa from upper and lower airways of
      cystic fibrosis patients.
AB  - A controversy exists concerning the adequate specimen to characterise
      colonisation of cystic fibrosis (CF) airways by Pseudomonas aeruginosa.
      Oropharyngeal, sputum and bronchoalveolar lavage samples were evaluated from 38
      stable CF patients for the detection of P. aeruginosa, genetically different
      isolates within the same host and longitudinal variations in the genotype during
      repeated examinations. Bacterial isolates were typed by pulsed-field gel
      electrophoresis of deoxyribonucleic acid macrorestriction fragments. Sensitivity,
      negative and positive predictive values and specificity to detect P. aeruginosa
      were 35.7, 73.5, 83.3 and 96.2% for oropharyngeal cultures in nonexpectorating
      patients and 91.7, 94.1, 100 and 100% for sputum cultures from expectorating
      patients, respectively. Genotypes of Pseudomonas isolates recovered from
      oropharyngeal swabs and sputum differed to the strains recovered by bronchoscopy
      in 55% and 40%, respectively. In 62% longitudinal variations in the genotype
      occurred. One-half of these alterations were detectable by bronchoscopy only. In
      conclusion, sputum samples were of equal value as specimens from bronchoalveolar
      lavage to detect Pseudomonas aeruginosa colonisation. Cultures from the
      oropharynx are not suitable for characterising bacterial conditions in the cystic
      fibrosis lung. Different genotypes within the same host and longitudinal genetic
      alterations are common and may be detectable in the bronchoalveolar lavage fluid
      exclusively.

PMID- 12503705
TI  - What predicts poor collection of medication among children with asthma? A case
      control study.
AB  - Compliance with asthma medication is recognised to be a problem. Acquisition of
      medication is the first step towards compliance. Factors predicting poor
      collection of prophylactic medication were investigated. A case/control study was
      conducted. Cases were children who had had at least two consultations for poorly
      controlled asthma in 1 yr and collected prescriptions of prophylactic medication
      irregularly. Controls were children whose prescriptions were collected as
      instructed. Levels of knowledge about asthma and asthma medication were high in
      both groups. Parents of cases were more likely to perceive their child's asthma
      to be moderate or severe and more likely to report that their child's asthma was
      not well controlled. They reported more night-time symptoms, exercise symptoms
      and school absence. Parents of cases were less likely to report that
      administering inhalers was part of the evening routine. They were less likely to
      perceive their child's prophylactic medication to be very effective and more
      reluctant to administer prophylactic medication. Some parents may decide to
      undertreat their children, although lack of organised routine may contribute to
      poor compliance. Parents need guidance on interpreting symptoms and support in
      establishing routines for the administration of medication.

PMID- 12503706
TI  - Children with mild asthma: do they benefit from inhaled corticosteroids?
AB  - In children with mild asthma, who show hardly any abnormalities in pulmonary
      function, objective measurement of the effect of inhaled corticosteroids is
      difficult. The short term effect of fluticasone propionate (FP) in these children
      was evaluated, using both subjective and objective parameters. A total of 68
      children (5-10 yrs old) were randomly assigned to either FP 250 microg or placebo
      twice daily as metered-dose inhaler via spacer during 12 weeks. Symptom scores,
      use of rescue medication, wheezing, parent global evaluation and pulmonary
      function tests including forced expiratory volume in one second (FEV1), peak
      expiratory flow (PEF) and bronchial responsiveness (provocation dose of
      methacholine causing a 20% fall in FEV1 (PD20)) were evaluated. FP-treated versus
      placebo-treated children showed significant changes in percentage symptom-free
      days, use of beta2-mimetics, morning and evening PEF, FEV1 % pred and wheezing.
      No significant improvements were found in parent global evaluation, absolute
      values of FEV1 nor PD20. These findings show that inhaled corticosteroids are
      effective in children with mild asthma. This effect can be assessed by both
      objective and subjective parameters. Early start of inhaled corticosteroids
      should be considered even when pulmonary function is normal.

PMID- 12503707
TI  - The management of childhood asthma in the community.
AB  - The aim of the present study was to assess the management of children with asthma
      in the community. Community-based random samples of children aged 5-7 and 9-11
      yrs in Dresden and Munich, Germany, were studied in 1995-1996 using the phase II
      protocol of the International Study of Asthma and Allergies in Childhood.
      Detailed information on the use of antiasthma drugs and accessory treatment in
      the past year was collected by parental questionnaire. A total of 11,094
      (response rate 83%) children participated. Among children with wheeze in the last
      year, 36% had used bronchodilators and 19% were on regular anti-inflammatory
      treatment. The strongest determinant of treatment was a physician's diagnosis of
      asthma. Forty-seven per cent of the children with current wheeze had not been
      diagnosed as asthmatics and received hardly any treatment (9% bronchodilators and
      2% anti-inflammatory drugs), despite an increased prevalence of severe asthma
      symptoms, bronchial hyperresponsiveness and atopic sensitisation compared with
      children without asthma symptoms. The proportion of children regularly using
      inhaled steroids was small (6%) among current wheezers and reached only 21% among
      children with diagnosed asthma and >12 wheezing attacks in the last year. Inhaled
      steroid use was lower in Munich than in Dresden and inversely related to the use
      of alternative remedies. Further efforts to improve the diagnosis and treatment
      of childhood asthma are needed. These should aim to increase awareness of the
      chronic nature of asthma and the need for treatment according to current
      guidelines.

PMID- 12503708
TI  - Nosocomial tracheobronchitis in mechanically ventilated patients: incidence,
      aetiology and outcome.
AB  - The aim of this study was to determine the incidence, the organisms responsible
      for and the impact on outcome of nosocomial tracheobronchitis (NTB) in the
      intensive care unit (ICU). This prospective observational cohort study was
      conducted in a 30-bed medical/surgical ICU over a period of 6.5 yrs. All patients
      ventilated for >48 h were eligible. Patients with nosocomial pneumonia (NP)
      without prior NTB were excluded. Patients with first episodes of NTB were
      compared with those without NTB by univariate analysis. The study diagnosed 201
      (10.6%) cases of NTB. Pseudomonas aeruginosa was the most common bacteria. NP
      rates were similar in patients with NTB compared with patients without NTB. Even
      in the absence of subsequent NP, NTB was associated with a significantly higher
      length of ICU stay and duration of mechanical ventilation in both surgical and
      medical populations. Mortality rates were similar in NTB patients without
      subsequent NP compared with patients without NTB. Antimicrobial treatment in NTB
      patients was associated with a trend to a better outcome. Nosocomial
      tracheobronchitis is common in mechanically ventilated intensive care unit
      patients. In this population, nosocomial tracheobronchitis was associated with
      longer durations of intensive care unit stay and mechanical ventilation. Further
      studies are needed to determine the impact of antibiotics on outcomes of patients
      with nosocomial tracheobronchitis.

PMID- 12503709
TI  - Effects of noninvasive ventilation on lung hyperinflation in stable hypercapnic
      COPD.
AB  - Two previous uncontrolled studies have suggested that noninvasive mechanical
      ventilation (NIMV) in patients with hypercapnic chronic obstructive pulmonary
      disease (COPD) improves arterial blood gas tensions by decreasing lung
      hyperinflation with the consequent reduction in inspiratory loads and changes in
      ventilatory pattern. The aim of this randomised placebo-controlled study was to
      determine whether these mechanisms play a pivotal role in the effects of NIMV on
      arterial blood gases. Thirty-six stable hypercapnic COPD patients were randomly
      allocated to NIMV or sham NIMV. A 2-week run-in period was followed by a 3-week
      study period, during which ventilation was applied 3 h x day(-1), 5 days a week.
      Arterial blood gases, spirometry, lung volumes, and respiratory mechanics were
      measured before and after application of NIMV. Patients submitted to NIMV showed
      changes (mean (95% confidence interval)) in daytime arterial carbon dioxide
      tension (Pa,CO2) and arterial oxygen tension of -1.12 (-1.52-0.73) kPa (-8.4 (
      11.4-5.5) mmHg) and 1.14 (0.70-1.50) kPa (8.6 (5.3-11.9) mmHg), respectively.
      Total lung capacity, functional residual capacity (FRC) and residual volume were
      found to be reduced by 10 (7-13), 25 (18-31), and 36 (27-45)% of their predicted
      value, respectively, whereas forced expiratory volume in one second and forced
      vital capacity increased by 4 (1.5-6.9) and 9 (5-13)% pred, respectively. Tidal
      volume (VT) increased by 181 (110-252) mL. All of the above changes were
      significant compared with sham NIMV. Changes in Pa,CO2 were significantly related
      to changes in dynamic intrinsic positive end-expiratory pressure, inspiratory
      lung impedance, VT and FRC. It was concluded that the beneficial effects of
      noninvasive mechanical ventilation could be explained by a reduction in lung
      hyperinflation and inspiratory loads.

PMID- 12503710
TI  - Partial liquid ventilation: effects of liquid volume and ventilatory settings on
      perfluorocarbon evaporation.
AB  - During partial liquid ventilation perfluorocarbons are eliminated mainly by
      evaporation via the airways. The effects of intrapulmonary perfluorocarbon
      volume, respiratory rate, tidal volume, as well as the level of end-expiratory
      pressure on perfluorocarbon elimination from isolated lungs, were studied.
      Nonperfused rabbit lungs underwent partial liquid ventilation (2-15 mL x kg(-1)
      perfluorocarbon) with variable levels of end-expiratory pressure (0-10 cmH2O),
      respiratory rates (15-60 breaths x min(-1)) and tidal volumes (3.3-10.0 mL x kg(
      1)). Evaporative loss of perfluorocarbon was determined gravimetrically as rate
      of change in lung weight. At constant respiratory settings, intrapulmonary liquid
      volume determined evaporative loss in a nonlinear fashion. Mean evaporation at a
      liquid volume of 5 mL x kg(-1) was 13% lower compared to evaporation at a liquid
      volume of 15 mL x kg(-1). Any increase in end-expiratory pressure reduced
      perfluorocarbon evaporation, e.g. by approximately 50% when end-expiratory
      pressure was increased from 0 to 10 cmH2O. At constant end-expiratory pressure
      and perfluorocarbon filling evaporation increased in a linear fashion with
      increasing respiratory rate and tidal volume. In summary, the experiments
      suggested that evaporative loss of perfluorocarbons during partial liquid
      ventilation of isolated lungs is increased with increasing intrapulmonary liquid
      volume, respiratory rate and tidal volume and is reduced in a level-dependent
      fashion by the application of positive end-expiratory pressure.

PMID- 12503711
TI  - Comparison of a cardiorespiratory device versus polysomnography for diagnosis of
      sleep apnoea.
AB  - This study assessed the accuracy of a cardiorespiratory monitoring device versus
      polysomnography for the diagnosis of suspected sleep apnoea/hypoponea syndrome
      (SAS). A total of 86 patients (89% male, mean age 52 yrs) that had been referred
      to a sleep laboratory with a clinical diagnosis of SAS underwent
      cardiorespiratory polygraphy in an unattended mode using an ambulatory device
      (MERLIN). Analysis was carried out both automatically and manually. Conventional
      overnight full-channel polysomnography was performed simultaneously. Valid
      polygraphical recordings were obtained from 79 patients. The mean+/-SD
      apnoea/hypopnoea index (AHI) was 34.4+/-29.2. The results obtained with manual
      scoring were superior to automatic scoring for all AHI thresholds. For an AHI of
      > or = 5, which is diagnostic SAS, the optimum cut-off value for the manual
      respiratory event index was 6.7 and the cardiorespiratory monitoring device had
      97.1% sensitivity and 90.9% specificity. Correct classification according to the
      different cut-off points obtained via polysomnography and the corresponding cut
      off points in the MERLIN manual index were confirmed in 90-96% of patients. The
      MERLIN device is a useful diagnostic approach for the initial assessment of adult
      patients with clinical suspicion of sleep apnoea/hypopnoea syndrome. Manual
      scoring is clearly better than automatic scoring in terms of agreement with the
      apnoea/hypopnoea index and to discern patients with sleep apnoea/hypopnoea
      syndrome.

PMID- 12503712
TI  - Mortality in severe sleep apnoea/hypopnoea syndrome patients: impact of
      treatment.
AB  - The aim of this study was to determine mortality in patients with sleep
      apnoea/hypopnoea syndrome (SAHS) according to the treatments employed and
      comorbidity. An historical cohort of patients with SAHS diagnosed at a university
      hospital between 1982 and 1992 and followed until 1996 was studied. From a total
      of 475 SAHS patients, 444 (94%), with a mean+/-SD apnoea/hypopnoea index at
      diagnosis of 55+/-27, were located and included in the study. SAHS treatments
      employed were: surgery (88), weight loss (134), continuous positive airway
      pressure (124) and 98 patients were not treated. By the end of follow-up, 49
      patients had died. According to Cox regression analysis, mortality in treated
      patients was lower than in those not treated, but higher in those with a history
      of severe chronic obstructive pulmonary disease. Mortality in nontreated patients
      compared with that of the general population, adjusted for age and sex, showed
      excessive mortality, which decreased in treated patients. Stratification by age
      showed a greater mortality rate ratio in patients <50 yrs. These findings were
      maintained when mortality from cardiovascular causes was compared. In conclusion,
      a rise in mortality was found in nontreated sleep apnoea/hypopnoea syndrome
      patients compared with the general population, whereas mortality in those treated
      for sleep apnoea/hypopnoea syndrome did not differ significantly from that of the
      general population.

PMID- 12503713
TI  - Ventricular mass index using magnetic resonance imaging accurately estimates
      pulmonary artery pressure.
AB  - Magnetic resonance imaging (MRI) can provide accurate anatomical measurements of
      the cardiac ventricles. This study investigated whether a calculated ventricular
      mass index (VMI) would provide an accurate means of estimating pulmonary artery
      pressure noninvasively, and compared the results with conventional Doppler
      echocardiography and invasive measurement. A total of 26 subjects referred for
      investigation of pulmonary hypertension were studied by MRI and echocardiography
      within 2 weeks of cardiac catheterisation. The correlations for mean pulmonary
      artery pressure were as follows: VMI (ratio of right ventricular mass over left
      ventricular mass) r=0.81; pulmonary artery systolic pressure (echocardiography)
      r=0.77. The confidence intervals for the VMI were narrower than for
      echocardiography. Sensitivity and specificity for pulmonary hypertension were 84
      and 71% respectively for the VMI compared with 89 and 57% for echocardiography.
      The calculated ventricular mass index provides an accurate and practical means of
      estimating pulmonary artery pressure noninvasively in pulmonary hypertension and
      may provide a more accurate estimate than Doppler echocardiography. This may be
      because it reflects the right ventricular response to sustained pulmonary
      hypertension over a long period and is not influenced by short-term physiological
      variables affecting echocardiography, such as heart rate, posture, hydration
      status and oxygen supplementation.

PMID- 12503714
TI  - Occupational and environmental risk factors for respiratory symptoms in rural
      Beijing, China.
AB  - The aim of the present study was to determine the effects of occupational and
      environmental exposure on respiratory symptoms in adults in rural Beijing, China.
      Thirty randomly selected villages in the counties of Shunyi and Tongxian, 50 km
      north and east, respectively, of the city of Beijing, China, participated in this
      study. Village doctors interviewed all residents aged > or = 15 yrs and completed
      the International Union Against Tuberculosis and Lung Disease Questionnaire on
      Bronchial Symptoms translated into Chinese with added questions on smoking and
      occupational and environmental exposure. Of the eligible population, 22,528
      adults (98%) took part. The prevalence of all respiratory symptoms, i.e. asthma
      like symptoms, asthma attacks in the last 12 months, chronic cough and chronic
      phlegm, was low. Significant determinants for respiratory symptoms were age, sex,
      smoking and county of residence. A dose-dependent relationship was found between
      cumulative cigarette consumption and prevalence of respiratory symptoms. After
      adjusting for these variables, exposure to insecticides and fertilisers
      significantly increased the risk of most of the respiratory symptoms, whereas
      exposure to indoor air pollution from domestic fuels did not. Exposure to
      chemicals such as insecticides and fertilisers contributed independently to the
      risk of respiratory symptoms in rural Beijing, China.

PMID- 12503715
TI  - Exhaled nitric oxide in specific challenge tests to assess occupational asthma.
AB  - Exhaled nitric oxide (NO) is a marker of eosinophilic inflammation of the airway
      mucosa accompanying changes in the clinical condition of asthma. Allergen
      exposure has been associated with delayed elevation of exhaled NO. The aim of
      this study was to assess the asthmatic airway inflammation with exhaled NO
      measurements during specific bronchial challenge tests with occupational agents.
      Forty patients with suspected occupational asthma were investigated. Specific
      bronchial challenge tests were performed with forced expiratory volume in one
      second or peak expiratory flow follow-up, supplemented by exhaled NO measurements
      before and 24 h after challenge tests. In active challenges, which induced
      bronchoconstriction, a significant mean increase of exhaled NO concentration was
      noted. In patients with a normal or slightly increased (<14.5 parts per billion
      (ppb)) basal NO level and a late bronchoconstriction, a significant increase in
      exhaled NO was seen. Patients with a high basal NO level (>14.5 ppb) and a
      significant bronchoconstriction did not show a significant NO elevation.
      Challenge tests without bronchoconstriction were not associated with a
      significant elevation of exhaled NO. Exhaled nitric oxide measurements can be
      used to indicate the development of airway inflammation accompanying late
      asthmatic reaction after bronchial challenge tests in patients with a normal or
      slightly increased basal nitric oxide concentration.

PMID- 12503716
TI  - Components of respiratory resistance monitored in mechanically ventilated
      patients.
AB  - The interrupter technique is commonly adopted to monitor respiratory resistance
      (Rrs,int) during mechanical ventilation; however, Rrs,int is often interpreted as
      an index of airway resistance (Raw). This study compared the values of Rrs,int
      provided by a Siemens 940 Lung Mechanics Monitor with total respiratory impedance
      (Zrs) parameters in 39 patients with normal spirometric parameters, who were
      undergoing elective coronary bypass surgery. Zrs was determined at the airway
      opening with pseudorandom oscillations of 0.2-6 Hz at end inspiration. Raw and
      tissue resistance (Rti) were derived from the Zrs data by model fitting; Rti and
      total resistance (Rrs,osc=Raw+Rti) were calculated at the actual respirator
      frequencies. Lower airway resistance (Rawl) was estimated by measuring tracheal
      pressure. Although good agreement was obtained between Rrs,osc and Rrs,int, with
      a ratio of 1.07+/-0.19 (mean+/-SD), they correlated poorly (r2=0.36). Rti and the
      equipment component of Raw accounted for most of Rrs,osc (39.8+/-11.9 and 43.0+/
      6.9%, respectively), whereas only a small portion belonged to Rawl (17.2+/-6.3%).
      It is concluded that respiratory resistance may become very insensitive to
      changes in lower airway resistance and therefore, inappropriate for following
      alterations in airway tone during mechanical ventilation, especially in patients
      with relatively normal respiratory mechanics, where the tissue and equipment
      resistances represent the vast majority of the total resistance.

PMID- 12503717
TI  - Physiology and pathophysiology of pleural fluid turnover.
AB  - Tight control of the volume and composition of the pleural liquid is necessary to
      ensure an efficient mechanical coupling between lung and chest wall. Liquid
      enters the pleural space through the parietal pleura down a net filtering
      pressure gradient. Liquid removal is provided by an absorptive pressure gradient
      through the visceral pleura, by lymphatic drainage through the stomas of the
      parietal pleura, and by cellular mechanisms. Indeed, contrary to what was
      believed in the past, pleural mesothelial cells are metabolically active, and
      possess the cellular features for active transport of solutes, including
      vesicular transport of protein. Furthermore, the mesothelium was shown, on the
      basis of recent experimental evidence, both in vivo and in vitro, to be a less
      permeable barrier than previously believed, being provided with permeability
      characteristics similar to those of the microvascular endothelium. Direct
      assessment of the relative contribution of the different mechanisms of pleural
      fluid removal is difficult, due to the difficulty in measuring the relevant
      parameters in the appropriate areas, and to the fragility of the mesothelium. The
      role of the visceral pleura in pleural fluid removal under physiological
      conditions is supported by a number of findings and considerations. Further
      evidence indicates that direct lymphatic drainage through the stomas of the
      parietal pleura is crucial in removing particles and cells, and important in
      removing protein from the pleural space, but should not be the main effector of
      fluid removal. Its importance, however, increases markedly in the presence of
      increased intrapleural liquid loads. Removal of protein and liquid by
      transcytosis, although likely on the basis of morphological findings and
      suggested by recent indirect experimental evidence, still needs to be directly
      proven to occur in the pleura. When pleural liquid volume increases, an imbalance
      occurs in the forces involved in turnover, which favours fluid removal. In case
      of a primary abnormality of one ore more of the mechanisms of pleural liquid
      turnover, a pleural effusion ensues. The factors responsible for pleural effusion
      may be subdivided into three main categories: those changing transpleural
      pressure balance, those impairing lymphatic drainage, and those producing
      increases in mesothelial and capillary endothelial permeability. Except in the
      first case, pleural fluid protein concentration increases above normal: this
      feature underlies the classification of pleural effusions into transudative and
      exudative.

PMID- 12503718
TI  - Pathobiology of pulmonary arterial hypertension.
AB  - Recent years have witnessed important advances in the understanding of the
      pathophysiology of primary pulmonary hypertension (PPH). Both genetic and
      mechanistic studies have succeeded in identifying new molecular pathways relevant
      to the process of pulmonary vascular remodelling, which underlies PPH. Mutations
      in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now
      considered to be the genetic basis for familial PPH and approximately 30% of
      cases of sporadic PPH. The identification of the relevance of the BMP pathway to
      the aetiology of PPH now raises many questions about the link between the BMPR-II
      mutant genotype and the PPH phenotype. As PPH does not develop in all subjects
      with BMPR-II mutations, environmental or associated genetic factors may play a
      crucial role. Among these, the finding of an association between PPH and the L
      allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT,
      which controls smooth muscle hyperplasia, probably contributes to susceptibility
      to PPH or is an important modifier of the PPH phenotype. Recognition of these
      molecular pathways should provide insight into the pathogenesis not only of
      primary pulmonary hypertension, but also of secondary forms of pulmonary
      hypertension. This should soon lead to the development of new and more selective
      therapeutic approaches to pulmonary hypertension.

PMID- 12503719
TI  - Infrastructure, funding and follow-up in a programme of noninvasive ventilation.
AB  - Originating from centres charged with the care of patients with chronic
      respiratory insufficiency, noninvasive ventilation (NIV) has been used
      increasingly in chronic and acute respiratory failure during the last decade.
      Despite a considerable number of series and randomised studies advocating access
      to NIV for units that treat acute or chronic ventilatory failure, the number of
      units and the proportion of total ventilatory support remains poor. This is due
      to lack of education, as many units treat only a few patients per year.
      Indication, technique, education, monitoring and home care require special
      experience and a special environment and there is a wide range throughout Europe.
      With respect to home care in particular, there are many organisations, which
      range from totally private to hospital based or run for profit. A concerted
      action, funded by the European Union, will soon provide valuable information
      about the practice of home ventilation in Europe based on a European survey.

PMID- 12503720
TI  - Effects of mechanical ventilation on diaphragm function and biology.
AB  - The pathophysiological mechanisms of weaning from mechanical ventilation are not
      fully known, but there is accumulating evidence that mechanical ventilation
      induces inspiratory muscle dysfunction. Recently, several animal models have
      provided potential mechanisms for mechanical ventilation-induced effects on
      muscle function. In patients, weaning difficulties are associated with
      inspiratory muscle weakness and reduced endurance capacity. Animal studies
      demonstrated that diaphragm force was already decreased after 12 h of controlled
      mechanical ventilation and this worsened with time spent on the ventilator.
      Diaphragmatic myofibril damage observed after 3-days controlled mechanical
      ventilation was inversely correlated with maximal diaphragmatic force.
      Downregulation of the diaphragm insulin-like growth factor-I and MyoD/myogenin
      messenger ribonucleic acid occurred after 24 h and diaphragmatic oxidative stress
      and increased protease activity after 18 h. In keeping with these findings,
      diaphragm fibre atrophy was shown after 12 h and reduced diaphragm mass was
      reported after 48 h of controlled mechanical ventilation. These animal studies
      show that early alterations in diaphragm function develop after short-term
      mechanical ventilation. These alterations may contribute to the difficulties in
      weaning from mechanical ventilation seen in patients. Strategies to preserve
      respiratory muscle mass and function during mechanical ventilation should be
      developed. These may include: adaptation of medication, training of the
      diaphragm, stabilisation of the catabolic state and pharmacotherapy.

PMID- 12503721
TI  - Paediatric respiratory training in Europe: syllabus and centres.

PMID- 12503722
TI  - Public health and medicolegal implications of sleep apnoea.

PMID- 12503723
TI  - Polyethylene flock-associated interstitial lung disease in a Spanish female.
AB  - This case study presents a female aged 54 yrs with a 12 months history of
      progressive pulmonary impairment after a 7-yr period of occupational exposure to
      rotary-cut polyethylene. An open lung biopsy revealed the histopathology of
      follicular bronchiolitis that is viewed as a stereotypical feature for flock
      worker's lung. It seems to be the first case of plastic flock-associated
      interstitial lung disease reported outside North America.

PMID- 12503724
TI  - Dyspnoea perception during clinical remission of atopic asthma.

PMID- 12503725
TI  - Cooperative effect of adenosine deaminase and ABO-secretor genetic complex on
      susceptibility to childhood asthma.

PMID- 12503726
TI  - Review of the 2002 Annual Meeting of the Biological Stain Commission.

PMID- 12503727
TI  - Microwave irradiation for rapid epidermis-dermis separation and improved
      epidermal cell immunodetection.
AB  - We explored the effects of microwave irradiation on epidermal-dermal separation
      and subsequent immunostaining of epidermal cells. Epidermal sheets were obtained
      after incubation in 0.02 M EDTA in PBS and microwave irradiation with 4 pulses of
      420 watts for 5 sec, with a total incubation period of 4 min. The control
      epidermal sheets were immunostained for Langerhans cells and dendritic epidermal
      T cells using a conventional immunoperoxidase method. The experimental
      immunodetection of these cells was assisted by incubating the primary antibodies
      for 10 min at 70 watts. We showed a simple and rapid method for separation of the
      epidermal-dermal junction and immunostaining of epidermal cells with optimal
      morphological preservation.

PMID- 12503728
TI  - An enzyme histochemical and biochemical study of the activity of three oxidative
      enzymes in the developing rat parotid gland.
AB  - Information on ductal differentiation in the developing rat parotid gland is
      sparse. One of the main functions of the striated and excretory ducts in this
      gland is the selective exchange of electrolytes from the primary fluid secreted
      by the acini. These ducts are rich in a number of enzymes involved in this task,
      suggesting that they might be useful as markers of ductal differentiation. The
      objective of this investigation was to delineate the developmental changes in
      activity of three of these, cytochrome C oxidase (CCO), succinate dehydrogenase
      (SDH), nicotinamide adenine phosphate dinucleotide (reduced form)-dehydrogenase
      (NADPH-DH). Histochemical localization of all three enzymes in fresh frozen
      sections was complemented by biochemical assays of CCO and SDH and cytochemical
      localization of CCO. Biochemically, CCO- and SDH-specific activity in gland
      homogenates increased progressively after birth, reaching adult levels at 21-28
      days. Histochemically, deposits of reaction products of all three enzymes
      increased more in the striated and excretory ducts, especially in their basal
      cytoplasm, than in other glandular structures between 19 days in utero and 28
      days after birth. During the same age span, the mitochondria in the striated and
      excretory ducts increased markedly in both number and size, migrated to a mostly
      basal location, and increased from many to virtually all showing strong
      cytochemical CCO reactions. These histochemical and cytochemical patterns of
      changes in enzyme activity at the cellular level accounted for the overall
      increases in CCO and SDH seen in the biochemical assays. Only the SDH
      histochemical reaction was consistently weak in the acini and intercalated ducts,
      and thus provided the most contrast with the progressively stronger reactions in
      the larger ducts. We conclude that of the three enzymes evaluated in these
      experiments, SDH is the best marker of the functional differentiation of the
      striated and excretory ducts in the developing rat parotid gland.

PMID- 12503729
TI  - A new stain for identification of avian leukocytes.
AB  - Differential staining of avian leukocytes was achieved within 6 min following
      brief fixation in a methanolic solution of C.I. acid red 360 followed by
      immersion in a mixture containing C.I. basic blue 41, C.I. basic blue 141, and
      C.I. acid red 52. Heterophils contained black angular and punctate granules.
      Eosinophils contained bright purple granules. Lymphocytes displayed red nuclei
      and blue cytoplasm. Monocytes contained red-brown nuclei and lavender cytoplasm.
      Basophils showed red-orange granules. Thrombocytes stained deep purple. Compared
      to traditional panoptic stains like Wright's or Giemsa's, the new staining method
      provides brighter colors, more precise details of cellular structures, and
      shorter staining time. Significantly, it facilitates identification of avian
      leukocyte species based on differences in color as well as differences in size
      and shape.

PMID- 12503730
TI  - Kinetic studies of glutaraldehyde binding in liver.
AB  - To study the kinetics of glutaraldehyde fixation, fresh rabbit liver cubes were
      immersed in 3% buffered 3H-glutaraldehyde for various periods of time. Following
      weighing and a brief rinse in water, the tissues were solubilized, and the
      radioactivity was measured in a scintillation counter. Binding of the isotope was
      half-maximal after approximately 4 h and a plateau was reached after
      approximately 20 h. We also investigated the reversibility of glutaraldehyde
      fixation. Fixed liver cubes were weighed and immersed in water for various
      periods of time, and after solubilization, the radioactivity was determined.
      After rinsing for 48 h, approximately 95% of the radioactivity was lost from the
      tissue specimens, indicating that fixation with glutaraldehyde is largely
      reversible. Light and electron microscopy of specimens rinsed for 1 and 48 h
      showed essentially similar morphology. Rinsing for 48 h restored some of the
      immunoreactivity that was absent after rinsing for only 1 h.

PMID- 12503731
TI  - Validation of image analysis for enzyme histochemical and immunocytochemical
      staining.
AB  - Immunocytochemical and enzyme histochemical analyses of cells and tissues are
      used to detect changes in the extent of injury and the expression of various
      molecules. Image analysis quantitation offers an easier, more efficient technique
      to evaluate these changes. We studied the application of image analysis for
      evaluating enzyme histochemistry and immunocytochemistry of cells and tissues as
      a way to assess stroke. Using brain sections, we compared investigator and
      computer-generated image analysis of 2,3,5-triphenyltetrazolium chloride stained
      cerebral infarcts in rats subjected to 2 h middle cerebral artery occlusion and
      22 h re-perfusion. Both methods documented the infarct volumes with a comparison
      of means of less then 5%. This suggests no difference between computer- and hand
      calculated values. Computer-generated analysis was easier and faster to use.
      Using endothelial cell monolayers, immunocytochemical staining of a time course
      of heat shock protein expression was compared to a grading system using fast red
      chromagen counterstained with hematoxylin. Results demonstrated greater ease and
      efficiency with computer-generated image analysis compared to other subjective
      systems of analysis. Image analysis is more useful for detecting small
      differences in staining, especially when using 3,3-diaminobenzidine as a
      chromagen. Investigator bias is also reduced using this system. Our comparisons
      validate the use of this versatile technology to assess more easily both cell and
      tissues in stroke research.

PMID- 12503732
TI  - Human pineal luteinizing hormone receptors.
AB  - The presence of luteinizing hormone receptors in human pineal glands from five
      females and three males, ranging in age from 61-89 yr, was examined by in situ
      hybridization and immunocytochemistry. The results demonstrated the presence of
      these receptors at the mRNA and protein levels in all the pineal glands examined.
      Pineal gland luteinizing hormone receptors could potentially be involved in the
      regulation of melatonin synthesis.

PMID- 12503733
TI  - Safe diaminobenzidine (DAB) disposal.

PMID- 12503734
TI  - Longitudinal sections of unfixed muscle.

PMID- 12503735
TI  - Color preservation in pathology museum specimens.

PMID- 12503736
TI  - Collagen type I staining.

PMID- 12503737
TI  - Processing dried out specimens.

PMID- 12503738
TI  - Suppressing autofluorescence.

PMID- 12503739
TI  - Effect of concentrated ambient particulate matter on blood coagulation parameters
      in rats.
AB  - Epidemiologic studies have shown that exposure to particulate air pollution is
      associated with short-term increases in cardiovascular morbidity and mortality.
      These adverse effects of inhaled particulate matter (PM*) may be the indirect
      result of a PM-induced increase in blood coagulability. This explanation is
      biologically plausible because prospective studies have shown that increases in
      blood coagulation parameters are significantly associated with risk of adverse
      cardiovascular events. We examined the hypothesis that acute exposure to elevated
      levels of PM causes prothrombotic changes in blood coagulation parameters. Rats
      with indwelling jugular vein catheters were exposed for 6 hours to filtered air
      or concentrated ambient PM in New York City air (n = 9 per group per experiment).
      PM less than 2.5 microm in mass median aerodynamic diameter (PM2.5) was
      concentrated for animal exposures using a centrifugal concentrator. Blood samples
      were taken at four time points: before and immediately after exposure and at 12
      and 24 hours after the start of exposure. At each time point, six coagulation
      parameters (platelet count, fibrinogen level, factor VII activity, thrombin
      antithrombin complex [TAT] level, tissue plasminogen activator [tPA] activity,
      and plasminogen activator inhibitor [PAI] activity) were measured as well as all
      standard blood count parameters. Five concentrated-PM exposure experiments were
      performed over a period of 8 weeks in the summer of 1999. PM exposure
      concentrations ranged from 95 to 341 microg/m3. Statistical significance was
      determined by two-way analysis of variance (ANOVA) on the postexposure data with
      time and exposure status as main effects. There were no consistent exposure
      related effects on any of the end points across the five experiments and no
      indication of any dose-dependent effects. Most of the statistically significant
      differences that were observed do not represent adverse effects. Therefore, the
      results of this study do not indicate that exposure to concentrated ambient PM
      causes adverse effects on blood coagulation in healthy rats.

PMID- 12503740
TI  - Analysis of arsenic bioavailability in contaminated soils.
AB  - The bioavailable arsenic (As) content of contaminated soils was determined by
      joint analyses of acid-soluble, total water-soluble, and biovailable As by using
      a luminescent bacterial sensor, Escherichia coli MC1061(pTOO31). According to the
      results of this study, a significant positive correlation was found between the
      concentration of total water-soluble As and the bioavailability of As. However,
      the bioavailability of As in soil varied between sampling sites and was not equal
      when compared to the concentration of total water-soluble As; bioavailable As was
      3 to 77% of total water-soluble As in soil. Our experiments also showed that
      aging and sequestration of As occurs in contaminated soils and As compounds thus
      become progressively less bioavailable with time. As a consequence, the
      bioavailability and toxicity of As should be considered when evaluating the
      ecological risks of contaminated soils.

PMID- 12503741
TI  - Dichlorodiphenyltrichloroethane in the aquatic ecosystem of the Okavango Delta,
      Botswana, South Africa.
AB  - Concentrations of DDT and its metabolites were measured in water, plants,
      invertebrates, and fish from lagoons in the Okavango Delta, Botswana (Africa),
      where DDT has been used for approximately 50 years. The sampling area was
      sectioned to distinguish spraying for malaria and for African sleeping sickness.
      Average concentrations of total DDT (sum of DDT and its metabolites) in the
      Okavango ranged from 0.009 ng/L in water to 18.76 ng/g wet weight in fish. These
      levels are approximately 1% of those found in piscivorous fish from temperate
      North America. The dichlorodiphenyl ethylene (DDE) metabolite was the most
      abundant fraction of total DDT. Although total DDT concentrations were higher in
      areas treated for malaria than areas treated for sleeping sickness, these
      concentrations were likely driven by factors other than the historic application
      of the pesticide. Equilibration with air concentrations is the most likely
      explanation for these levels. Since the mean annual temperature exceeds the
      temperature of vaporization of DDT, this research points to the need for reliable
      transport models. Our results showed that total DDT concentration in fish was
      best explained by lipid content of the fish and trophic position inferred by
      delta15N, regardless of DDT application history in those areas. The reservoir
      above Gaborone Dam, an area downstream of the Okavango but where DDT had not been
      used, was sampled to compare total DDT levels to the treated areas. The two
      species (a herbivorous threespot talapia and the omnivorous sharptooth catfish)
      from Gaborone had levels higher than those found in the Okavango Delta, but these
      differences can again be explained using trophic position inferred by delta15N
      rather than by fish size or location.

PMID- 12503742
TI  - Transport behavior of 3,3'-dichlorobenzidine in a freshwater estuary.
AB  - Like many hydrophobic organic compounds, 3,3'-dichlorobenzidine (DCB) partitions
      preferentially to (sediment) particles in lake systems. As such, the behavior of
      DCB in these systems is substantially affected by the movement of sediments. A
      field investigation of DCB distribution in sediments of Lake Macatawa (Holland,
      MI, USA) was initiated. The pattern of DCB distribution within the lake was found
      to display an oscillatory pattern that was consistent with a wind-driven
      mechanism of sediment transport. Numerical modeling of seiching behavior
      supported the hypothesized importance of this mechanism of sediment transport and
      redistribution. The dynamic behavior of sediment-associated DCB within Lake
      Macatawa seems to be strongly influenced by phenomena that are common to many
      freshwater estuaries. As such, the behavior of this system is expected to
      represent a reasonable model of the dynamic behavior of hydrophobic contaminants
      in other freshwater estuaries.

PMID- 12503743
TI  - Development and application of a generalized physiologically based
      pharmacokinetic model for multiple environmental contaminants.
AB  - The pharmacological disposition of four environmental contaminants resulting from
      acute and chronic exposure regimes is simulated using a general physiologically
      based pharmacological (PBPK) model. The model, which is detailed in supporting
      materials, is mechanistic in structure and relies on available physical-chemical
      partitioning and reactivity data, but experimental partitioning and absorption
      efficiency data can be used to refine the parameters. It is designed to
      complement environmental fate models, thus linking chemical emission rates with
      environmental and physiological behavior as part of the larger environmental risk
      assessment process. The model is illustratively applied to inhaled styrene and
      trichloroethene as well as ingested dibutyl phthalate and di(2-ethylhexyl)
      phthalate. The phthalate simulations include the corresponding monoester and
      conjugated monoester as metabolites. Tissue concentrations for each of the
      chemicals and metabolites are simulated for acute, occupational, and
      environmental exposure regimes. The same model is used for all chemicals and
      exposure regimes with only the physical-chemical properties, reaction rates, and
      exposure estimates being changed.

PMID- 12503744
TI  - Effects of linear alkylbenzene sulfonates on functional diversity of microbial
      communities in soil.
AB  - Linear alkylbenzene sulfonates (LAS) often occur in sewage sludge that is applied
      to agricultural soil. Here LAS may affect the microbial activity, which is an
      important basis for nutrient cycling. Previous studies have shown that single
      bacterial species and specific soil processes can be very sensitive to LAS. Here
      we report that two levels of LAS, 22 and 174 mg/kg dry weight soil, had little or
      no significant influence of the functional diversity of bacteria in a sandy soil,
      as tested by community-level physiological profiles. Briefly, these profiles are
      a characterization of the microbial communities based on the pattern of substrate
      utilization in 96-well microtiter plates (Biolog EcoPlates). Sandy agricultural
      soil was incubated in duplicate 1-L mesocosms with or without LAS, and bacteria
      were extracted after one, two, and four weeks. During incubation, more than 98
      and 93% of LAS added to 22 and 174 mg/kg dry weight soil was degraded,
      respectively. The presence of LAS at 174 mg/kg dry weight caused a higher number
      of bacteria in the soil extracts, maximally corresponding to 2.5 times the
      numbers in LAS-free soil (1.8 x 10(7) cells/g dry wt soil) after four weeks of
      incubation. No inhibitory effect of LAS was observed when the substrate
      utilization data were analyzed for substrate richness and diversity (Shannon
      Weaver indices). Principal component analysis, however, showed that the pattern
      of substrate utilization in soil with the highest LAS content (174 mg/kg dry wt)
      could be distinguished from control soil and soil with 22 mg LAS/kg dry weight.
      Yet the overall conclusion was that the functional diversity of the aerobic,
      heterotrophic bacterial community was rather insensitive to LAS.

PMID- 12503745
TI  - The effect of aging on pyrene transformation in sediments.
AB  - The effect of aging on pyrene transformation and pyrene association with
      fractions of the sedimentary organic matrix (SdOM) was evaluated using [4,9
      (13)C2]pyrene. Sediments were collected from a site of previous petroleum
      hydrocarbon contamination (New Orleans, LA, USA). Aged sediments were autoclaved
      for 1 h, amended with pyrene, and then stored in the dark in a 0.05% NaN3
      solution for 120 d. Both aged and nonaged sediments were incubated in aerated
      microcosms for 120 d. Microcosms were acidified to collect evolved carbon dioxide
      (CO2); sediments were fractionated and lipid extracted to quantify pyrene in SdOM
      fractions. Cross-polarization magic angle spinning 13C-nuclear magnetic resonance
      (CPMAS 13C-NMR) spectra indicated that synthetic aging techniques did alter SdOM
      structure to some degree, but these changes did not affect SdOM affinity for
      pyrene. Aging delayed pyrene mineralization and increased pyrene concentrations
      extracted from bulk sediment and humic fractions. Aging also reduced the toxicity
      of sediment humin. Pyrene-4,5-dione and pyrene cis-4,5-dihydrodiol were
      identified in extracts of aged sediments by 13C-NMR and gas chromatography mass
      spectrometry, respectively.

PMID- 12503746
TI  - Determination of polycyclic aromatic hydrocarbons in dungeness crabs (Cancer
      magister) near an aluminum smelter in Kitimat Arm, British Columbia, Canada.
AB  - An aluminum smelter situated at the head of Kitimat Arm (BC, Canada) has
      discharged polycyclic aromatic hydrocarbons (PAHs) into the receiving waters
      since 1954. The purpose of the present study was to examine the distribution of
      PAHs contaminants in dungeness crabs (Cancer magister) collected in Kitimat Arm
      and Douglas Channel (BC, Canada) by determining the concentrations of PAHs in the
      hepatopancreas and muscle tissues of crabs by using gas chromatography-mass
      spectrometry. Crabs were collected at specific sites down the Arm from the
      smelter on four separate occasions over a three-year period. Hepatopancreas and
      muscle tissues of the crabs were analyzed for 10 of the 16 PAH priority
      pollutants recommended by the U.S. Environmental Protection Agency. Results of
      the studies showed that the crabs had detectable levels of PAHs in hepatopancreas
      and muscle tissues. The highest concentrations of PAHs in the tissues were found
      at a site near the aluminum smelter, the alleged point source of PAH discharge.
      The concentrations of PAH analytes were high in crabs collected close to the
      smelter and at lower levels in crabs collected throughout Douglas Channel. These
      results show that PAHs discharged by the smelter were bioavailable to the crabs.
      The concentration of each PAH analyte in the hepatopancreas was found to be
      strongly related to its water solubility. However, the PAH analyte concentrations
      in the hepatopancreas and muscle did not appear to correlate highly with each
      other.

PMID- 12503747
TI  - Screening pyrene metabolites in the hemolymph of dungeness crabs (Cancer
      magister) with synchronous fluorescence spectrometry: method development and
      application.
AB  - The present study examined the metabolic pathways of pyrene in dungeness crabs
      (Cancer magister) in the laboratory and the potential of using synchronous
      fluorescence spectrometry (SFS) to determine pyrene metabolite concentrations in
      the hemolymph of crabs exposed to polycyclic aromatic hydrocarbons (PAHs) in the
      field. Pyrene was metabolized by crabs mainly to 1-hydroxypyrene and pyrene-1
      glucoside. Both pyrene metabolites could be detected by SFS in the hemolymph of
      crabs. A nondestructive hemolymph collection procedure was developed and used in
      conjunction with the SFS assay to assess the exposure of crabs to PAHs in Kitimat
      Arm (British Columbia, Canada). Our results showed that crabs obtained near the
      source of PAH contamination had the highest level of pyrene-related fluorescence
      in the hemolymph, whereas concentrations were lower at other sites downstream
      from the pollution source. In a separate study, the hepatopancreases of crabs
      were analyzed for parent PAHs by using gas chromatography-mass spectrometry.
      Pyrene-associated fluorescent responses of the hemolymph were found to correlate
      positively with the concentration of total PAHs in the hepatopancreas (r = 0.39,
      p < 0.05).

PMID- 12503748
TI  - The fate, distribution, and toxicity of lindane in tests with Chironomus
      riparius: effects of bioturbation and sediment organic matter content.
AB  - In this laboratory study, we address the effect of Chironomus bioturbation (0,
      2,000, 6,000, and 18,000 ind/m2) and sediment organic matter content (10, 20, and
      40%) on the fate, distribution, and bioavailability of 14C-lindane under
      standardized conditions in toxicity tests with artificial sediment. The results
      show that both Chironomus burrowing activity and sediment organic matter strongly
      modify test conditions. Larval mortality and development were inversely related
      with Chironomus densities and lindane concentration. Sediment organic matter
      content affected larval development rates but not mortality. Partitioning of
      lindane between the sediment, overlying water, and interstitial water was
      affected negatively by Chironomus larval densities: however, sediment
      partitioning was positively affected by sediment organic matter content.
      Bioturbation by Chironomus resulted in a remobilization of particle-associated
      lindane to the interstitial and overlying water, implying an increase in the
      bioavailability of the test compound. Strong positive relationships were found
      between Chironomus densities and lindane concentrations in interstitial water.
      The presence of Chironomus also resulted in lower label recovery. Label recovery
      on sediment particles ranged from 49 to 61% of initially added label in
      microcosms without Chironomus, from 41 to 56% at low larval densities, and from
      15 to 50% at high larval densities. These results show that large discrepancies
      may exist between nominal test concentrations (from test compound additions) and
      true exposure concentrations even under standardized test conditions, which can
      introduce a relatively large error term in risk assessments. Calculations show
      that volatilization may be a quantitatively important sink for test compounds.

PMID- 12503749
TI  - Reduction of estrogenic activity of municipal wastewater by aerated lagoon
      treatment facilities.
AB  - The estrogenic activity of municipal wastewater in aerated lagoon treatment
      facilities was evaluated using plasma concentrations of vitellogenin (Vtg) in
      male fathead minnows (Pimephales promelas). Caged fathead minnows were exposed
      for 10 to 12 d in three lagoons that are connected in series at each of 10
      municipal wastewater treatment facilities in central Iowa, USA, during October
      and November 2000. Fathead minnows held in the laboratory served as unexposed
      controls. Pooled (n = 4-10 fish) plasma Vtg, quantified by enzyme-linked
      immunosorbent assay (ELISA), was 1,702 +/- 670 (mean +/- standard error [SE])
      microg/ml in the first lagoons (n = 9), 0.94 +/- 0.36 microg/ml in the second
      lagoons (n = 10), and 0.04 +/- 0.02 microg/ml in the third lagoons (n = 8).
      Differences in mean fish plasma Vtg concentration among lagoons were highly
      significant (p < 0.001). The mean concentration of plasma Vtg in fish in the
      third lagoons was not significantly different (p = 0.990) from that of the
      control fish (0.04 +/- 0.02 microg/ml). Plasma Vtg concentrations of fish in the
      first lagoons were inversely correlated with wastewater retention time in the
      lagoons (p = 0.002, r = -0.877). Water temperatures of the final effluents during
      the study ranged from 9 to 12 degrees C. General treatment efficiency of lagoons
      has been shown to be dependent on temperature, so the potential exists for
      decreased removal of estrogenic activity when water temperatures are lower (e.g.,
      winter months) than the present study. In conclusion, wastewater entering aerated
      lagoon systems was estrogenic to fish, but with serial passage through the
      lagoons, the estrogenic activity decreased to a level that was not sufficient to
      induce vitellogenesis in male fathead minnows in a 10- to 12-d exposure.

PMID- 12503750
TI  - Toxicity evaluation of a commercial bioremediation agent mixed with crude oil.
AB  - The toxicity and efficacy of a bacteria-based commercial bioremediation agent
      (CBA) was assessed through bioassays with juvenile inland silverside minnows,
      Menidia beryllina, and flask studies of oil degradation. Addition of the CBA to
      weathered Alaska, USA North Slope crude oil (ANS-521) prior to testing increased
      toxicity of the water-soluble fraction (WSF) of the oil in both chronic (growth)
      and acute (mortality) toxicity tests. Time-course toxicity assessment of the
      water-soluble fraction of the CBA/oil combination indicated increases in effect
      after 7 to 14 d of mixing that coincided with elevated concentrations of both
      alkanes and aromatics in the WSF. Under controlled laboratory conditions, the CBA
      significantly enhanced degradation of the oil compared with a treatment with
      nutrients alone. The alkane fraction was degraded by nearly 100% over a 42-d
      period while the aromatic fraction was decreased by 70%. While toxicity testing
      is not currently required to list bioremediation agents on the product schedule
      of the National Oil and Hazardous Substances Pollution Contingency Plan, the
      potential interaction between bioremediation agents and oil should be further
      investigated and listing requirements reassessed as necessary. Recommendations
      for future investigations of this issue include characterization of temporal
      trends in toxicity of CBA and oil mixtures, use of multiple test methods (battery
      testing) when evaluating toxicity, comparative evaluations of indigenous versus
      product-derived microorganisms in efficacy studies, and the use of a comparable
      oil between studies to facilitate comparison of efficacy and toxicity data for
      different products.

PMID- 12503751
TI  - Oxidative stress biomarkers in bivalves transplanted to the Guadalquivir estuary
      after Aznalcollar spill.
AB  - Biological effects of metals were studied in clams (Scrobicularia plana)
      transplanted to Guadalquivir estuary (Spain) at several times after the spill of
      toxic metals from Aznalcollar pyrite mine (southwest Spain) (April 1998) using
      biochemical biomarkers responsive to reactive oxygen species. Significant As, Cd,
      Fe, Mn, Ni, and Pb uptake was found in clams living for seven months at the
      estuary (from July 1999). Increased activity of antioxidant (catalase, glucose-6
      phosphate, and 6-phosphogluconate dehydrogenase) and glutathione-related
      (glutathione reductase and glyoxalase I and II) enzymes was also found after
      short exposures; the levels of malondialdehyde and metallothionein increased
      also, particularly with long exposures. Clams living four weeks at the estuary
      (from March 2000) but not at a reference site also accumulated metals. The higher
      malondialdehyde and lower reduced-glutathione levels and the more oxidized
      glutathione status confirmed the oxidative stress of clams living at the estuary,
      while no marked increase of antioxidant activities was found this time. Lower
      metal availability along the second transplant could explain the limited
      responses in this shorter experiment. Although the status of Guadalquivir estuary
      has recovered since Aznalcollar spill, continuous monitoring is needed to confirm
      its progress and to be alert to possible deterioration after heavy rains.

PMID- 12503752
TI  - Immunosuppression in the northern leopard frog (Rana pipiens) induced by
      pesticide exposure.
AB  - An injection study and a field study were used to investigate the hypothesis that
      environmental xenobiotics have the potential to alter the immune function of
      northern leopard frogs (Rana pipiens). Three assays, IgM-specific antibody
      response to keyhole limpet hemocyanin linked to dinitrophenyl (KLH-DNP), zymozan
      induced chemiluminescence (CL) of whole blood and the delayed-type
      hypersensitivity (DTH), were used to assay humoral, innate and cell-mediated
      immune endpoints. Sublethal doses of DDT (923 ng/g wet wt), malathion (990 ng/g
      wet wt), and dieldrin (50 ng/g wet wt) were used in the injection study. In all
      pesticide-injected groups, antibody response was dramatically suppressed, DTH
      reactions were enhanced, and respiratory burst was lower. When the order of
      administration of pesticides and antigens was reversed, no differences in immune
      function between the control and dosed groups were apparent, indicating that
      frogs exposed to pathogens prior to pesticide exposure can still respond. A field
      study found significant differences in immune function between frog populations
      in pesticide-exposed and pesticide-free locations. The antibody response and CL
      were suppressed and the DTH enhanced in frogs from Essex County (ON, Canada).
      Overall, the results suggest that exposure to these pesticides can cause both
      stimulatory and suppressive immune changes in adult frogs and is doing so in wild
      populations.

PMID- 12503753
TI  - Construction and evaluation of a transgenic hsp16-GFP-lacZ Caenorhabditis elegans
      strain for environmental monitoring.
AB  - A novel integrated transgenic Caenorhabditis elegans strain (PC161) incorporates
      a double reporter construct with green fluorescent protein (GFP) and lacZ genes
      fused in-frame into the second exon of the hsp16-1 gene. This construct also
      includes the Simian Virus 40 (SV40) nuclear localization signal such that the
      fusion protein accumulates in the nuclei of expressing cells. The PC161 strain
      was used to monitor the effects of several known stressors, including heat,
      cadmium, and microwave radiation. The time course of induction was similar for
      both reporters but was strongly influenced by pretreatment conditions. The PC161
      worms kept at 15 degrees C beforehand showed a steady increase in reporter
      expression (up to at least 16 h) when heated to 30 degrees C. However, if washed
      on ice prior to heat stress at 30 degrees C, PC161 worms showed a much steeper
      rise in reporter expression, reaching a maximum after 2.5 h and then plateauing.
      Heat shock induced strong expression of both reporter genes in all tissues apart
      from the germ line and early embryos. A highly significant linear dose-response
      relationship was observed for both transgenes with increasing cadmium
      concentrations (5-100 microg/ml). Prolonged exposure to microwave radiation (750
      MHz and 0.5 W for 16 h) also induced expression of both transgenes at 25 and (to
      some extent) 27 degrees C, but only beta-galactosidase activity was detectable at
      23 degrees C, and neither reporter was detectably expressed at 21 degrees C.
      Throughout all exposures, the lacZ reporter product was more readily detectable
      than coexpressed GFP. However, the GFP reporter affords opportunities to monitor
      the stress response in living worms.

PMID- 12503754
TI  - Plasma cholinesterase levels of mountain plovers (Charadrius montanus) wintering
      in central California, USA.
AB  - Declines of over 60% in mountain plover (Charadrius montanus) populations over
      the past 30 years have made it a species of concern throughout its current range
      and a proposed species for listing under the U.S. Endangered Species Act.
      Wintering mountain plovers spend considerable time on freshly plowed agricultural
      fields where they may potentially be exposed to anticholinesterase pesticides.
      Because of the population status and wintering ecology of plovers, the objectives
      of our study were to use nondestructive methods to report baseline plasma
      cholinesterase (ChE) levels in free-ranging mountain plovers wintering in
      California, USA, and to assess whether sampled birds showed signs of ChE
      inhibition related to anticholinesterase chemical exposure. We compared plasma
      ChE activity for mountain plovers sampled from the Carrizo Plain (an area
      relatively free of anticholinesterase pesticide use) with similar measures for
      plovers from the Central Valley (where anticholinesterase pesticides are widely
      used). Analyses for ChE inhibition indicated that none of the plovers had been
      recently exposed to these chemicals. However, mean ChE levels of plovers from the
      Central Valley were significantly higher (32%) than levels reported for plovers
      from the Carrizo Plain. This result differs from our original assumption of
      higher exposure risk to mountain plovers in the Central Valley but does suggest
      that some effect is occurring in the ChE activity of mountain plovers wintering
      in California.

PMID- 12503755
TI  - Assessment and characterization of polychlorinated biphenyls near a hazardous
      waste incinerator: analysis of vegetation, snow, and sediments.
AB  - Samples of spruce needles, snowpack, and sediment were analyzed in the area
      around the Alberta Special Waste Treatment Centre (ASWTC) near Swan Hills,
      Canada, in 1997 and 1998, following a major accidental release of polychlorinated
      biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) in
      October 1996. The PCB concentrations in spruce needles and snow were mostly
      elevated to the east of the plant and contained congeners that were not present
      at upwind or distant sites. Several years of annual vegetation monitoring data
      indicated that PCB emissions increased prior to the reported accident. Within 3
      km of the plant, there was a predominance of higher chlorinated congeners penta-,
      hexa-, hepta-, and octachlorobiphenyls in white spruce (Picea glauca) needles and
      snow. Polychlorinated biphenyl congener patterns varied seasonally in spruce
      needles, likely influenced by temperature effects on the volatilization and of
      particle-bound and vapor phase PCBs in the forest canopy. The similarity of
      deposition patterns in snow and needles in 1997 and 1998 suggested the PCBs in
      the surrounding area were derived by long-term fugitive releases of PCBs rather
      than an accidental release. In addition, hexachlorobenzene, a combustion by
      product of chlorinated organics in waste incinerators, was not measured at
      elevated concentrations in spruce needles or snow east of the facility and, when
      detected, was not correlated with PCB concentrations. A radiometrically dated
      sediment core from nearby Chrystina Lake (AB, Canada) showed a gradual increase
      in annual PCB flux during the early years of operation of the ASWTC, followed by
      a higher PCB flux in 1997, indicating that the lake may have been directly
      contaminated by the accidental release.

PMID- 12503756
TI  - Studies of the environmental fate and effect of aircraft deicing fluids:
      detection of 5-methyl-1H-benzotriazole in the fathead minnow (Pimephales
      promelas).
AB  - This paper presents the results of a number of field and laboratory studies to
      evaluate the environmental impact of aircraft deicing and anti-icing fluids
      (ADAFs) on aquatic systems. Both 5-methyl-1H-benzotriazole (5-MeBt) and 4-methyl
      1H-benzotriazole (4-MeBt), known additives to ADAFs, were found in whole-tissue
      extracts from minnows placed downstream of an effluent outfall that receives ADAF
      contaminated runoff from General Mitchell International Airport (Milwaukee, WI,
      USA). Neither of these compounds was detected in tissues from minnows placed
      upstream from the airport. A toxicity assessment of water collected during the
      minnow exposure studies utilizing Hyalella azteca, Pimephales promelas, and
      Ceriodaphnia dubia showed greater toxicity in a secondary airport outfall
      containing ADAFs when compared to upstream non-ADAF-contaminated samples. In two
      28-d static renewal tests using 5-MeBt laboratory-fortified waters, 5-MeBt was
      detected in whole-tissue extracts of minnows at all concentrations tested. In
      studies using laboratory water fortified with 5-MeBt, the median lethal
      concentration (LC50) of 5-MeBt for P. promelas was found to be 22.0 mg/L. The
      LC50 for C. dubia to 5-MeBt laboratory-fortified water was found to be 81.3 mg/L.
      The 25% inhibition concentration (IC25) of 5-MeBt for the green alga Selenastrum
      capricornutum was 23.2 mg/L, and the average median effective concentration
      (EC50) for Microtox was 4.25 mg/L. The results of these field and lab studies
      indicate that additives, other than glycols, used in aircraft deicing fluids can
      be found in aquatic systems and may be of greater risk than previously believed.

PMID- 12503757
TI  - Tributyltin causes masculinization in fish.
AB  - We examined the effect of tributyltin (TBT) on the sex differentiation process in
      genetically female Japanese flounder (Paralichthys olivaceus). The fish were fed
      an artificial diet containing tributyltin oxide (TBTO) at concentrations of 0.1
      and 1.0 microg/g diet from 35 to 100 d after hatching, which includes the sex
      differentiation period. The ratio of sex-reversed males significantly increased
      to 25.7% of the flounder fed the 0.1 microg/g diet and to 31.1% of those fed the
      1.0 microg/g diet compared with the control (2.2%). From morphological and
      histological examination of the fish in the TBT-treated groups, normal females
      had typical ovaries and sex-reversed males had typical testes. These results
      clearly demonstrated the masculinization of flounder exposed to TBTO. This is the
      first report of TBT inducing sex reversal in vertebrates.

PMID- 12503758
TI  - Toxicity of triphenyltin and tributyltin to the freshwater mudsnail Potamopyrgus
      antipodarum in a new sediment biotest.
AB  - The effects of two suspected endocrine-disrupting chemicals, the xeno-androgens
      triphenyltin (TPT) and tributyltin (TBT), were investigated in a new whole
      sediment biotest with the freshwater mudsnail Potamopyrgus antipodarum
      (Gastropoda, Prosobranchia). Artificial sediments were spiked with seven
      concentrations, ranging from 10 to 500 microg nominal TPT-Sn/kg dry weight and
      TBT-Sn/kg dry weight, respectively. We analyzed the responses of the test species
      after two, four, and eight weeks exposure. For both compounds, P. antipodarum
      exhibited a sharp decline in the number of embryos sheltered in its brood pouch
      in a time- and concentration-dependent manner in comparison to the control
      sediment. The number of new, still unshelled embryos turned out to be the most
      sensitive parameter. The lowest-observed-effect concentration (LOEC) was
      equivalent to the lowest administered concentration (10 microg/kg of each test
      compound) for most parameters and thus no no-observed-effect concentration (NOEC)
      could be established. The calculation of effect concentrations (EC10) resulted in
      even lower values for both substances (EC10 after eight weeks for unshelled
      embryos: 0.03 microg TPT-Sn/kg, EC10 after four weeks for unshelled embryos: 0.98
      microg TBT-Sn/kg). Our results indicate that P. antipodarum is highly sensitive
      to both endocrine disruptors TPT and TBT at environmentally relevant
      concentrations.

PMID- 12503759
TI  - Bioavailability of desorption-resistant phenanthrene to the oligochaete
      Ilyodrilus templetoni.
AB  - We investigated bioavailability, as measured by the biota-sediment accumulation
      factor (BSAF), of reversibly sorbed and desorption-resistant phenanthrene to the
      deposit-feeding freshwater tubificid oligochaete Ilyodrilus templetoni.
      Desorption-resistant, phenanthrene-contaminated sediments were prepared by a
      sequential batch desorption method by washing with an isopropanol solution. The
      BSAFs averaged 1.20 +/- 0.32 and 0.59 +/- 0.13 for reversibly sorbed phenanthrene
      and desorption-resistant phenanthrene, respectively, indicating a significantly
      reduced bioavailability of desorption-resistant phenanthrene. A generalized model
      assuming a linear relationship between pore-water concentration and normalized
      bioaccumulation described 91% of the variance for both measured and selected
      literature data of the BSAF. The reduced bioavailibility of desorption-resistant
      phenanthrene was thus well described by physical and chemical measures of
      partitioning between pore water and sediment.

PMID- 12503760
TI  - Toxicity of aqueous and sediment-associated fluoride to freshwater organisms.
AB  - Inorganic fluorides were declared toxic under the Canadian Environmental
      Protection Act in 1993 based on their potential to cause long-term harmful
      effects in aquatic and terrestrial ecosystems, but information on the toxicity of
      sediment-associated fluoride to freshwater benthic organisms was considered
      incomplete. The purpose of this study was to determine the toxicity of aqueous
      and sediment-associated fluoride to several species of freshwater organisms and
      to determine if toxic effects could be expected under environmentally realistic
      exposures. Toxicity of fluoride (as NaF) in short-term (48-96-h) lethality tests
      was greatest for the amphipod Hyalella azteca (median lethal concentration [LC50]
      = 14.6 mg F-/L), followed by the mayfly Hexagenia limbata (32.3), the midge
      Chironomus tentans (124.1), the fathead minnow Pimephales promelas (262.4), and
      the cladoceran Daphnia magna (282.8). Relative toxicity in long-term (10-28-d)
      growth and survival tests in spiked sediment was similar. Hyalella azteca was the
      most sensitive species for growth (25% inhibitory concentration [IC25] = 290.2
      microg F-/g), followed by C. tentans (661.4), H. limbata (1,221.3), and P.
      promelas (>5,600); H. azteca was also the most sensitive species for survival
      (LC50 = 1,114.6 microg F-/g), followed by H. limbata (1,652.2) and P. promelas
      and C. tentans (>5,600 for both). Concentrations of fluoride measured in
      sediments near some industrial point sources exceed some of these toxicity
      thresholds. Fluoride is highly mobile in aquatic systems and could potentially
      reach toxic levels in the water column during dredging to remove fluoride
      contaminated sediment.

PMID- 12503761
TI  - ICON rice seed treatment toxicity to crayfish (Procambarus clarkii) in
      experimental rice paddies.
AB  - Outdoor pools (2.3 x 2.3 m) were used to simulate typical rice agricultural
      practices in Louisiana, USA, to evaluate the toxicity of ICON (active ingredient
      [a.i.] fipronil) and its degradates to crayfish (Procambarus clarkii). Six
      paddies were planted with seed treated with ICON 6.2 FS at an exaggerated
      application rate of 0.05 kg a.i./ha (recommended rate, 0.042 kg a.i./ha),
      simulating three rice-planting scenarios. Two reference paddies were planted with
      untreated seed. Crayfish were exposed to tail water within 24 to 48 h after
      seeding, simulating standard Louisiana agricultural and water management
      practices. At 50 d after planting, a separate group of crayfish was caged in situ
      for 14 d to evaluate toxicity. An additional 50 crayfish were added to two
      paddies approximately 100 d after rice planting and held for 29 weeks to evaluate
      bioaccumulation. Residues of fipronil and its degradates in water and soil were
      similar to residue concentrations measured from rice fields in Louisiana. Tail
      water from the treated paddies was not toxic to crayfish. The fipronil 96-h
      median lethal concentration (LC50) for adult crayfish was 180 microg/L, which
      would provide at least a sixfold safety factor between the maximum fipronil
      concentration in tail water and the crayfish LC50. In situ exposures of crayfish
      also were not toxic. Concentrations of fipronil and its degradates after 29 weeks
      of exposure were less than 5 microg/kg in crayfish tail muscle tissue. These
      results demonstrate that label instructions adequately protect crayfish in a rice
      crayfish cropping scenario when ICON is applied at maximum application rates as a
      seed treatment.

PMID- 12503762
TI  - Developing transgenic Arabidopsis plants to be metal-specific bioindicators.
AB  - Deoxyribonucleic acid (DNA) microarrays provide a means to assess genome-wide
      expression patterns after exposure of an organism to different xenobiotics.
      Potential uses for this technology include identification of unknown toxicants,
      assessment of toxicity of new compounds, and characterization of the cellular
      mechanisms of toxicant action. Here we describe another use of DNA microarrays in
      toxicant-specific gene discovery. Combining results from two DNA microarray
      experiments, we have identified genes from the model plant Arabidopsis thaliana
      that are induced in response to one but not other heavy metals. The promoters of
      these genes should be useful in developing metal-specific transgenic biomonitors.
      To test this idea, we have fused the promoter of one of the newly identified Ni
      inducible genes (AHB1) to the beta-glucuronidase (GUS) reporter gene. Arabidopsis
      plants containing the AHBI::GUS transgene show reporter gene activity when they
      are grown on media containing Ni but not when grown on media containing Cd, Cu,
      Zn, or without added metals. Thus, this approach has resulted in the creation of
      a transgenic strain of Arabidopsis that can report on the presence and
      concentration of Ni in plant growth media. Such transgenic models can serve as
      cheap and efficient biomonitors of bioavailable heavy metal contamination in
      soils and sediments.

PMID- 12503763
TI  - Controlled release experiments with nonylphenol in aquatic microcosms.
AB  - A method of controlled release of technical nonylphenol (tNP) was developed to
      simulate realistic exposure in ecotoxicological studies on aquatic organisms. The
      direct addition of tNP from an aqueous stock solution into 50 ml of water led to
      a concentration decrease of 80 to 90% weight/volume (w/v) from nominal values
      within 48 h. The inclusion of tNP in semipermeable low-density polyethylene
      (LDPE) lay-flat tubing (controlled-release devices [CRDs]) of different length
      allowed a continuous release into pure water at a rate of about 30 microg/cm2/d.
      Using CRDs in aquaria containing 15 L of 63-microm-filtered lake water, eight
      different concentrations with maxima between 38.1 and 326.7 microg/L were
      maintained for 11 d. During a second experiment in 15-L aquaria, five replicates
      of three concentrations were maintained using CRDs of the same length.
      Concentrations after 38 d varied between 0.1 and 6.7, 26.1 and 41.9, and 49.9 and
      76.0 microg/L. In aquatic microcosms containing 230 L of lake water, a natural
      plankton community, 50 L of sediment, and macrophytes, seven different tNP
      concentrations (maxima 11-120.1 microg/L) were maintained over 45 d using CRDs of
      different length. They were replaced after 14 and 25 d because release of tNP was
      slower than predicted from laboratory experiments. Concentrations in the top 1-cm
      sediment layer were on average 19 times higher during the dosing period than
      concentrations in the water at the same time. In the sediments, different levels
      of applications led to concentrations that differed less distinctly than in the
      water. This method is suitable for exposing aquatic organisms continuously to
      constant, ecologically relevant concentrations of NP and represents an
      improvement over previous dosing methods in which exposure varied.

PMID- 12503764
TI  - Dietary accumulation of perfluorinated acids in juvenile rainbow trout
      (Oncorhynchus mykiss).
AB  - Perfluorinated acids (PFAs) recently have emerged as persistent global
      contaminants after their detection in wildlife and humans from various geographic
      locations. The highest concentrations of perfluorooctane sulfonate are
      characteristically observed in high trophic level organisms, indicating that PFAs
      may have a significant bioaccumulation potential. To examine this phenomenon
      quantitatively, we exposed juvenile rainbow trout (Oncorhynchus mykiss)
      simultaneously to a homologous series of perfluoroalkyl carboxylates and
      sulfonates for 34 d in the diet, followed by a 41-d depuration period. Carcass
      and liver concentrations were determined by using liquid chromatography-tandem
      mass spectrometry, and kinetic rates were calculated to determine compound
      specific bioaccumulation parameters. Depuration rate constants ranged from 0.02
      to 0.23/d, and decreased as the length of the fluorinated chain increased.
      Assimilation efficiency was greater than 50% for all test compounds, indicating
      efficient absorption from food. Bioaccumulation factors (BAFs) ranged from 0.038
      to 1.0 and increased with length of the perfluorinated chain; however, BAFs were
      not statistically greater than 1 for any PFA. Sulfonates bioaccumulated to a
      greater extent than carboxylates of equivalent perfluoroalkyl chain length,
      indicating that hydrophobicity is not the sole determinant of PFA accumulation
      potential and that the acid function must be considered. Dietary exposure will
      not result in biomagnification of PFAs in juvenile trout, but extrapolation of
      these bioaccumulation parameters to larger fish and homeothermic organisms should
      not be performed.

PMID- 12503765
TI  - Bioconcentration and tissue distribution of perfluorinated acids in rainbow trout
      (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) were exposed simultaneously to a homologous
      series of perfluoroalkyl carboxylates and sulfonates in a flow-through system to
      determine compound-specific tissue distribution and bioconcentration parameters
      for perfluorinated acids (PFAs). In general, PFAs accumulated to the greatest
      extent in blood > kidney > liver > gall bladder. Carboxylates and sulfonates with
      perfluoroalkyl chain lengths shorter than seven and six carbons, respectively,
      could not be detected in most tissues and were considered to have insignificant
      bioconcentration factors (BCFs). For detectable PFAs, carcass BCFs increased with
      increasing length of the perfluoroalkyl chain, ranging from 4.0 to 23,000, based
      on wet weight concentrations. Carboxylate carcass BCFs increased by a factor of
      eight for each additional carbon in the perfluoroalkyl chain between 8 and 12
      carbons, but this relationship deviated from linearity for the longest PFA
      tested, possibly because of decreased gill permeability. In general, half-lives
      (3.9-28 d) and uptake rates (0.053-1.700 L/kg/d) also increased with increasing
      length of the perfluoroalkyl chain in all tissues. Sulfonates had greater BCFs,
      half-lives, and rates of uptake than the corresponding carboxylate of equal
      perfluoroalkyl chain length, indicating that hydrophobicity, as predicted by the
      critical micelle concentration, is not the only determinant of PFA
      bioaccumulation potential and that the acid function must be considered.

PMID- 12503766
TI  - Effects of pulp and paper mill effluents on reproductive success of largemouth
      bass.
AB  - This study evaluated the effects of bleached and unbleached kraft mill effluent
      on reproductive success of largemouth bass (Micropterus salmoides). Bass were
      exposed to effluent concentrations (0, 10, 20, 40, or 80%) for 28 and 56 d.
      Parameters measured included hepatosomatic index (HSI) and gonadosomatic index
      (GSI) and plasma concentrations of 17beta-estradiol (E2), 11-ketotestosterone (11
      KT), and vitellogenin (VTG). At the end of the 56-d period, bass were moved to
      hatchery ponds to evaluate spawning success. Spawning mats with eggs either were
      brought indoors for evaluation of fecundities, hatchabilities, and egg and fry
      size (measured at age 3 d), or were left in ponds and fry number and size
      recorded (average age of 14 d). Effluent exposure was verified by measuring resin
      acids (isopimaric, abietic. and dehydroabietic acids) in bile. Compared to
      controls, exposed bass had greater concentrations of resin acids in bile. In
      general, exposed females had lower concentrations of E2 and VTG (> or = 20%
      effluent), whereas males had lower concentrations of 11-KT (> or = 20% effluent)
      and increased E2 (> or = 20% effluent). The HSI values increased in females (> or
      = 10% effluent), and GSI values decreased in both sexes (> or = 40% effluent).
      Fecundity, egg size, and hatchability did not differ across treatments, but an
      increase in the frequency of fry abnormalities and a decrease in fry weights was
      observed at effluent exposures of 40% and higher. However, results from the pond
      study, revealed a significant reduction in fry growth and survival (> or = 10%).
      This decline may have been caused by an increased frequency of deformities, in
      conjunction with alterations of growth. These changes could have resulted from
      alterations in egg quality because of failure of parental reproductive systems,
      from acute embryo toxicity after translocation of contaminants from the mother to
      the developing embryo, or from both.

PMID- 12503767
TI  - Selected resin acids in effluent and receiving waters derived from a bleached and
      unbleached kraft pulp and paper mill.
AB  - Water samples were collected on three dates at 24 sites influenced by effluent
      from Georgia-Pacific's Palatka Pulp and Paper Mill Operation, a bleached and
      unbleached kraft mill near Palatka, Florida, USA. The sampling sites were located
      within the mill retention ponds, Rice Creek, and the St. John's River. Samples
      were analyzed by gas chromatography-mass spectrometry for abietic,
      dehydroabietic, and isopimaric acids, all of which are potentially toxic by
      products of pulp production. Isopimaric acid concentrations greater than 12 mg/L
      were measured at the mill's effluent outfall but were less than 20 microg/L at
      the end of Rice Creek. This result indicates that the waters of Rice Creek
      provide dilution or conditions conducive for degradation or sorption of these
      compounds. Large differences in resin acid concentrations were observed between
      sampling events. In two sampling events, the maximum observed concentrations were
      less than 2 mg/L for each analyte. In a third sampling event, all of the
      compounds were detected at concentrations greater than 10 mg/L. Data from the
      three sample dates showed that resin acid concentrations were below 20 microg/L
      before the confluence of Rice Creek and the St. John's River in all cases.

PMID- 12503768
TI  - Impact of atrazine on aneuploidy in pacific oysters, Crassostrea gigas.
AB  - Aneuploidy has previously been described and studied in the Pacific oyster,
      Crassostrea gigas, and has been shown to be negatively correlated with growth.
      The present study investigated the effect of atrazine on the level of aneuploidy
      in this species. Crassostrea gigas adults and juveniles were subjected to
      different concentrations of atrazine representing a peak value found in a
      polluted environment (46.5 nM) and a value 10 times higher (465 nM). Although
      atrazine did not show any effect on the oyster mortality, significant differences
      in aneuploidy level were observed between the different treatments (9% for the
      control, 16% for 46.5 nM and 20% for 465 nM atrazine). Moreover, the same levels
      of aneuploidy were observed at adult and juvenile stages. This is the first
      reported evidence for an environmental effect on aneuploidy in C. gigas. These
      results will be useful for the oyster aquaculture industry and management of
      resources. The lowest atrazine level in the current study represents realistic
      potential exposure, and the results suggest that studies should be made on other
      aquatic species at risk of exposure to atrazine in the wild. This widely used
      compound may be an important factor causing damage to genetic material.

PMID- 12503769
TI  - Pyrene biotransformation products as biomarkers of polycyclic aromatic
      hydrocarbon exposure in terrestrial Isopoda: concentration-response relationship,
      and field study in a contaminated forest.
AB  - In this study, biotransformation products of pyrene were measured in the
      hepatopancreas of terrestrial isopods as biomarkers of polycyclic aromatic
      hydrocarbon (PAH) exposure. These products--pyrene-1-glucoside, pyrene-1-sulfate,
      an unknown pyrene conjugate, and 1-hydroxypyrene--were quantitated using high
      performance liquid chromatography (HPLC) with fluorescence detection. In a
      controlled exposure experiment, a linear relationship was established between
      pyrene exposure and pyrene metabolite concentrations in the hepatopancreas of
      Porcellio scaber Latr. To this end, isopods of the species P. scaber were exposed
      to a range of pyrene concentrations spiked to their food. A linear response was
      found for all pyrene conjugates in the range 0.67 to 67 microg/g of pyrene (dry
      wt). Hepatopancreatic pyrene metabolite concentrations were also measured in
      isopods (P. scaber and Oniscus asellus L.) from PAH-contaminated field sites. The
      sites and the inhabiting isopods were located in a gradient of atmospheric PAH
      deposition caused by a nearby blast furnace plant. The highest levels of
      conjugated 1-hydroxypyrene in the hepatopancreas were 3.8 pmol/g fresh weight
      (pyrene-1-glucoside) and 2.8 pmol/g fresh weight (pyrene-1-sulfate) (expressed on
      whole-body basis). The levels of the pyrene metabolites correlate with reported
      pyrene concentrations in spite of these sites. As pyrene is one of the most
      predominant PAHs, analysis of its metabolites provides a good tool for
      environmental risk assessment of ecosystems with regard to PAH exposure,
      bioavailability, and biotransformation.

PMID- 12503770
TI  - Observations of tissue response to acoustic radiation force: opportunities for
      imaging.
AB  - Acoustic Radiation Force Impulse (ARFI) imaging is a method for characterizing
      local variations in tissue mechanical properties. In this method, a single
      ultrasonic transducer array is used to both apply temporally short localized
      radiation forces within tissue and to track the resulting displacements through
      time. In an ongoing study of the response of tissue to temporally short radiation
      force excitation, ARFI datasets have been obtained of ex vivo tissues under
      various focal configurations. The goal of this paper is to report observations of
      the response of tissue to radiation force and discuss the implications of these
      results in the construction of clinical imaging devices.

PMID- 12503771
TI  - A modified block matching method for real-time freehand strain imaging.
AB  - This manuscript reports a technical innovation that has been developed for real
      time, freehand strain imaging. This work is based on a well-known block-matching
      algorithm with two significant modifications. First, since displacements are
      estimated row-by-row, displacement estimates from the previous row are used to
      predict the displacement estimates in the current row, thereby drastically
      reducing the search-region size and increasing computational efficiency. Second,
      a displacement error detection and correction method is developed to overcome the
      local tracking errors that may be more severe with freehand scanning and thereby
      improve the robustness of the algorithm. This algorithm has been implemented on a
      clinical ultrasound imaging system, and with real-time imaging feedback, long
      sequences of high quality strain images are observed using freehand compression.
      Displacement estimation errors with this method are experimentally measured and
      compared with results from simulation. We report only a specific implementation,
      with no comparison to other displacement estimators in the literature and no
      optimization of this specific technique. Images of tissue-mimicking phantoms with
      small spherical targets are used to test the ability to detect small lesions
      using the strain imaging technique. In vivo strain images of breast and thyroid
      are also shown.

PMID- 12503772
TI  - Circular antenna for breast ultrasonic diffraction tomography.
AB  - Compared to echography, which exploits only the reflected field, ultrasonic
      diffraction tomography improves image resolution by combining the total
      diffracted field. For breast cancer imaging, this improvement reinforces contrast
      between various breast tissues and structures by eliminating some interference
      phenomena such as speckle and then allowing parameterization of the images. Our
      work concerns the development of an experimental set-up for fast acquisition of
      the diffracted field and construction of two-dimensional tomographic images. For
      this purpose, we developed a multichannel ultrasound circular antenna with eight
      focused transducers.

PMID- 12503773
TI  - Effects of three H2-receptor antagonists (cimetidine, famotidine, ranitidine) on
      serum gastrin level.
AB  - We investigated the pattern of changes in serum gastrin level produced by three
      H2-receptor antagonists (H2RA) in patients with gastric and duodenal ulcers
      between 1990 and 1999. The subjects were 51 patients (cimetidine: 18 patients;
      famotidine: 16 patients; ranitidine: 17 patients). The gastrin test (in the
      fasting and meal-stimulated states) was conducted during drug administration and
      on the fourth day after drug cessation. After cessation of the drug therapy, the
      fasting serum gastrin level was significantly lower than that during the drug
      therapy with the three H2RAs. Gastrin level in the fasting test was significantly
      higher during famotidine therapy than during cimetidine therapy (p = 0.0123). In
      the meal-stimulated gastrin test, the AUC of gastrin during treatment with H2RA
      treatment was significantly higher with famotidine than with cimetidine (p =
      0.0024). The results indicate different patterns of change in the serum gastrin
      level in the fasting and meal-stimulated test according to the H2RA administered.
      Gastrin level was highest in patients administered famotidine and lowest among
      those administered cimetidine. The pattern of gastrin change in patients
      administered ranitidine was intermediate between famotidine and cimetidine.

PMID- 12503774
TI  - Pharmacokinetics and bioavailability of four modified-release ursodeoxycholic
      acid preparations for once-a-day administration.
AB  - Ursodeoxycholic acid (UDCA) is currently used for the treatment of cholestatic
      liver disease and for cholesterol gallstone dissolution. Various formulations
      have been designed to enhance its intestinal absorption or to improve patient
      compliance through once-a-day administration. The pharmacokinetics and
      bioavailability of four commercially available modified-release UDCA formulations
      (450 mg) were studied in 12 healthy subjects randomly receiving the four drugs
      under study. Serum samples were collected hourly for a 12-h period after
      administration and UDCA concentrations were measured using a specific enzyme
      immunoassay. For each formulation, Cmax, tmax, and the area under the curve (AUC)
      were determined and compared. Although all formulations were designed to provide
      sustained release, we observed different pharmacokinetics among the studied
      formulations. One of the formulations (sustained-release ursodeoxycholic acid
      Ratiopharm 450 mg tablets) showed high bioavailability, but failed to produce
      sustained release. In contrast, two other formulations (modified-release
      ursodeoxycholic acid Dorom 450 mg capsules and controlled-release Ursobil HT 450
      mg capsules) provided sustained release, but did not offer efficient
      bioavailability. A fourth formulation (Ursilon retard 450 mg) exhibited gradual
      UDCA release lasting over 10 h, with efficient bioavailability, similar to that
      of conventional prompt-release formulations administered at the same dose. These
      data highlight the variability of commercially available sustained-release
      formulations. Manufacturers should be encouraged to provide drug kinetics and
      bioavailability data to further support the claimed pharmacokinetics.

PMID- 12503775
TI  - Paclitaxel-ifosfamide for anthracycline-resistant advanced breast cancer.
AB  - Thirty-one patients with advanced breast cancer either resistant to anthracycline
      based regimens or relapsing after anthracycline-based adjuvant chemotherapy
      received a combination of a 3-h infusion of paclitaxel 135 mg/m2 on day 1 and a 4
      h infusion of ifosfamide 1.7 g/m2 on days 2 to 4 of a 22-day cycle. For inclusion
      in the study, patients had to have measurable or evaluable progressive metastasis
      or local disease, and to have received only one prior regimen for metastatic
      disease; 31 patients with a median age of 49 years (range: 30-69) entered the
      study. Nine patients (29%) had lung metastasis, while 17 (55%) had liver
      metastasis, and 19 (61%) had bone metastasis. Only seven patients (23%) had lymph
      node metastasis and four (13%) had skin metastasis. A median of seven cycles of
      treatment was delivered. Responses were evaluated according to World Health
      Organization (WHO) guidelines and side effects according to National Cancer
      Institute (NCI) criteria. A panel of oncologists and one radiologist reviewed all
      responses. At baseline, only three patients (10%) were free from the adverse
      effects of the prior therapy; severe nonhematological toxicity occurred in less
      than 8% of patients. However neutropenia grade 3-4 occurred in 88%, while only 3%
      had severe infections. Severe thrombocytopenia and anemia were rare (4% and 8%,
      respectively). The overall response rate was 42% (13% complete response). Median
      survival and progression-free survival rates after initiation of treatment were
      19.3 months and 6.1 months, respectively. With an objective response rate of 42%
      and median survival of 19 months, the combination of paclitaxel and ifosfamide
      seems to offer a promising regimen with acceptable side effects in advanced
      breast cancer patients relapsing after anthracycline-based adjuvant treatment or
      resistant to anthracycline treatment.

PMID- 12503776
TI  - Comparison of the efficacy, safety and tolerability of original policosanol
      versus other mixtures of higher aliphatic primary alcohols in patients with type
      II hypercholesterolemia.
AB  - This randomized, double-blind study was undertaken to compare the efficacy and
      tolerability of policosanol and Octa-60 in patients with type II
      hypercholesterolemia. After 4 weeks on a diet, 110 patients were randomized to
      policosanol or Octa-60 5 mg tablets once a day for 5 weeks. The dose was then
      doubled to 10 mg/day for the next 5 weeks. Policosanol 5 and 10 mg/day
      significantly lowered low-density lipoprotein-cholesterol (LDL-C) (p<0.0001 and
      p<0.00001), the main efficacy variable, by 18.6% and 30.2%, while Octa-60
      significantly reduced (p<0.05) LDL-C by 10.0% at study completion only. The
      frequency of policosanol patients reaching reductions of LDL-C > or = 15% after 5
      mg/day (37/55; 67.3%) and 10 mg/day (47/55; 88.7%) was greater (p<0.01 and
      p<0.01) than in the Octa-60 group, which was 5/55 (9.1%) and 20/55 (36.4%).
      Likewise, the frequency of patients reaching LDL-C values of <3.4 mmol/l at study
      completion was greater (p<0.001) in the policosanol group (39/55, 70.9%) than in
      the Octa-60 group (6/55, 10.9%). Policosanol 5 and 10 mg/day significantly
      lowered (p<0.00001) total cholesterol (TC) (13.4% and 20.4%), LDL-C/high-density
      lipoprotein-cholesterol (HDL-C) (22.1% and 37.0%) and TC/HDL-C (17.2% and 28.2%).
      Octa-60 at 10 mg/day lowered (p<0.05) TC (8.7%), LDL-C/HDL-C (12.6%) and TC/HDL-C
      (9.4%). HDL-C was increased (p<0.001 and 0.0001) by policosanol 5 and 10 mg/day
      (5.6% and 12.5%) but was unchanged by Octa-60. In both groups, triglycerides
      remained unchanged. Both treatments were safe and well tolerated. Octa-60, but
      not policosanol, significantly increased glucose and alanine aminotransferase,
      but individual values were within the normal range. Four patients (two from each
      group) discontinued the trial, but only one (in the Octa-60 group) did so because
      of an adverse event (AE) (skin rash). Overall, three patients (all from the Octa
      60 group) reported AEs. In conclusion, original policosanol at 5 and 10 mg/day,
      but not Octa 60, was effective in patients with type II hypercholesterolemia.
      Thus, policosanol reached the efficacy criterion for LDL-C reduction in both
      steps, while Octa-60 failed to reach this goal. In addition, policosanol was
      better tolerated than Octa-60.

PMID- 12503777
TI  - Improving signal reliability for on-line joint angle estimation from nerve cuff
      recordings of muscle afferents.
AB  - Closed-loop functional electrical stimulation (FES) applications depend on
      sensory feedback, thus, it is important to continuously investigate new methods
      to obtain reliable feedback signals. The objective of the present paper was to
      examine the feasibility of using an artificial neural network (ANN) to predict
      joint angle from whole nerve cuff recordings of muscle afferent activity within a
      physiological range of motion. Furthermore, we estimated how small changes in
      joint angle that can be detected from the nerve cuff recordings. Neural networks
      were tested with data obtained from ten acute rabbit experiments in simulated, on
      line experiments. The electroneurograms (ENG) of the tibial and peroneal nerves
      were recorded during passive ankle joint rotation. To decrease the joint angle
      prediction error with new rabbit data, we attempted to pretune the nerve signals
      and re-trained the ANNs with the pretuned data. With these procedures we were
      able to compensate for interrabbit variability. On average the mean prediction
      errors were less than 2.0 degrees (a total excursion of 20 degrees) and we were
      able to predict joint angles from muscle afferent activity with accuracy close to
      the best-estimated angular resolution. The angular resolution was found to depend
      on the initial joint angle and the actual step size taken and we found that there
      was a low probability of detecting joint angle changes less than 1.5 degrees. We
      thus suggest that muscle afferent activity is applicable as feedback in real-time
      closed-loop control, when the motion speed is restricted and when the movement is
      limited to a portion of the joint's physiological range.

PMID- 12503778
TI  - A new brain-computer interface design using fuzzy ARTMAP.
AB  - This paper proposes a new brain-computer interface (BCI) design using fuzzy
      ARTMAP (FA) neural network, as well as an application of the design. The
      objective of this BCI-FA design is to classify the best three of the five
      available mental tasks for each subject using power spectral density (PSD) values
      of electroencephalogram (EEG) signals. These PSD values are extracted using the
      Wiener-Khinchine and autoregressive methods. Ten experiments employing different
      triplets of mental tasks are studied for each subject. The findings show that the
      average BCI-FA outputs for four subjects gave less than 6% of error using the
      best triplets of mental tasks identified from the classification performances of
      FA. This implies that the BCI-FA can be successfully used with a tri-state
      switching device. As an application, a proposed tri-state Morse code scheme could
      be utilized to translate the outputs of this BCI-FA design into English letters.
      In this scheme, the three BCI-FA outputs correspond to a dot and a dash, which
      are the two basic Morse code alphabets and a space to denote the end (or
      beginning) of a dot or a dash. The construction of English letters using this tri
      state Morse code scheme is determined only by the sequence of mental tasks and is
      independent of the time duration of each mental task. This is especially useful
      for constructing letters that are represented as multiple dots or dashes. This
      combination of BCI-FA design and the tri-state Morse code scheme could be
      developed as a communication system for paralyzed patients.

PMID- 12503779
TI  - Intelligent stretching of ankle joints with contracture/spasticity.
AB  - An intelligent stretching device was developed to treat the spastic/contractured
      ankle of neurologically impaired patients. The device stretched the ankle safely
      throughout the range of motion (ROM) to extreme dorsiflexion and plantarflexion
      until a specified peak resistance torque was reached with the stretching velocity
      controlled based on the resistance torque. The ankle was held at the extreme
      position for a period of time to let stress relaxation occur before it was
      rotated back to the other extreme position. Stretching was slow at the joint
      extreme positions, making it possible to reach a larger ROM safely and it was
      fast in the middle ROM so the majority of the treatment was spent in stretching
      the problematic extreme ROM. Furthermore, the device evaluated treatment outcome
      quantitatively in multiple aspects, including active and passive ROM, joint
      stiffness and viscous damping and reflex excitability. The stretching resulted in
      considerable changes in joint passive ROM, stiffness, viscous damping and reflex
      gain. The intelligent control and yet simple design of the device suggest that
      with appropriate simplification, the device can be made portable and low cost,
      making it available to patients and therapists for frequent use in clinics/home
      and allowing more effective treatment and long-term improvement.

PMID- 12503780
TI  - Control of leg-powered paraplegic cycling using stimulation of the lumbo-sacral
      anterior spinal nerve roots.
AB  - We investigated leg-powered cycling in a recumbent tricycle for a paraplegic
      using functional electrical stimulation (FES) with the lumbo-sacral anterior root
      stimulator implant (LARSI). A female complete T9 paraplegic had a stimulator for
      the anterior L2 to S2 spinal roots (bilaterally) implanted in 1994. She was
      provided with equipment for daily FES cycling exercise at home. The cycling
      controller applies a pattern of stimulation in each of 16 crank angle phases. A 7
      bit shaft encoder measures the crank angle with adequate precision. Each pattern
      was originally chosen to give the greatest propulsive force in that position when
      there was no motion. However, dynamically, some reduction in co-contraction is
      needed; also the patterns are applied with a preset advance time. Maximal power
      is obtained with an advance of 250 ms, which compensates for muscle response
      delay and accommodates changes in cadence (from about 25 to 85 rpm). With this
      system, she has cycled 1.2 km at a time on gently undulating road. We found that
      spinal root stimulation gives sufficient control over the muscles in the legs to
      produce a fluid cycling gait. We propose that root stimulation for leg cycling
      exercise may be a practicable and valuable function for paraplegics following
      spinal cord injury.

PMID- 12503781
TI  - Development of a quantitative reflex hammer for measurement of tendon stretch
      reflex.
AB  - Quantification of tendon stretch reflex requires precise measurement of the
      tapping force of a reflex hammer. A quantitative reflex (QR) hammer consisting of
      two cut rubber pieces from a generic rubber reflex hammer and a uniaxial force
      transducer was constructed. Finite element stress analyses were conducted to
      estimate the natural frequency characteristics of the hammer and to find the
      stress distributions during the impact. Pendulum impact testing was conducted at
      four different heights to assess the calibration linearity and repeatability of
      the measurement. The QR hammer had a fundamental natural frequency of 515 Hz and
      showed minimal displacement and stress at the tip from the finite element
      simulation of the impact. The QR hammer also provided reliable and repeatable
      measurements as demonstrated with high coefficients of determination, exceeding
      0.994 and small coefficients of variations, less than 4%. The calibration
      linearity was 0.64% compared with the reference force platform measurement. The
      QR hammer demonstrated sufficient accuracy and reliability for precise clinical
      assessment of tendon stretch reflexes.

PMID- 12503782
TI  - Feature selection for the classification of movements from single movement
      related potentials.
AB  - Classification of movement-related potentials recorded from the scalp to their
      corresponding limb is a crucial task in brain-computer interfaces based on such
      potentials. Many features can be extracted from raw electroencephalographic
      signals to be used for classification, but the utilization of irrelevant or
      superfluous features is detrimental to the performance of classification
      algorithms. It is, therefore, necessary to select a small number of relevant
      features for the classification task. This paper demonstrates the use of two
      feature selection methods to choose a small number (10-20) of relevant features
      from a bank containing upward of 1000 features. One method is based on
      information theory and the other on the use of genetic algorithms. We show that
      the former is poorly suited for the aforementioned classification task and
      discuss the probable reasons for this. However, using a genetic algorithm on data
      recorded from five subjects we demonstrate that it is possible to differentiate
      between the movements of two limbs with a classification accuracy of 87% using as
      little as 10 features without subject training. With the addition of a simple
      coding scheme, this method can be applied to multiple limb classification and a
      63% classification accuracy rate can be reached when attempting to distinguish
      between three limbs.

PMID- 12503783
TI  - Development of a robotic device for facilitating learning by children who have
      severe disabilities.
AB  - This paper presents technical aspects of a robot manipulator developed to
      facilitate learning by young children who are generally unable to grasp objects
      or speak. The severity of these physical disabilities also limits assessment of
      their cognitive and language skills and abilities. The CRS robot manipulator was
      adapted for use by children who have disabilities. Our emphasis is on the
      technical control aspects of the development of an interface and communication
      environment between the child and the robot arm. The system is designed so that
      each child has user control and control procedures that are individually adapted.
      Control interfaces include large push buttons, keyboards, laser pointer, and head
      controlled switches. Preliminary results have shown that young children who have
      severe disabilities can use the robotic arm system to complete functional play
      related tasks. Developed software allows the child to accomplish a series of
      multistep tasks by activating one or more single switches. Through a single
      switch press the child can replay a series of preprogrammed movements that have a
      development sequence. Children using this system engaged in three-step sequential
      activities and were highly responsive to the robotic tasks. This was in marked
      contrast to other interventions using toys and computer games.

PMID- 12503784
TI  - Discrimination of walking patterns using wavelet-based fractal analysis.
AB  - In this paper, we attempted to classify the acceleration signals for walking
      along a corridor and on stairs by using the wavelet-based fractal analysis
      method. In addition, the wavelet-based fractal analysis method was used to
      evaluate the gait of elderly subjects and patients with Parkinson's disease. The
      triaxial acceleration signals were measured close to the center of gravity of the
      body while the subject walked along a corridor and up and down stairs
      continuously. Signal measurements were recorded from 10 healthy young subjects
      and 11 elderly subjects. For comparison, two patients with Parkinson's disease
      participated in the level walking. The acceleration signal in each direction was
      decomposed to seven detailed signals at different wavelet scales by using the
      discrete wavelet transform. The variances of detailed signals at scales 7 to 1
      were calculated. The fractal dimension of the acceleration signal was then
      estimated from the slope of the variance progression. The fractal dimensions were
      significantly different among the three types of walking for individual subjects
      (p < 0.01) and showed a high reproducibility. Our results suggest that the
      fractal dimensions are effective for classifying the walking types. Moreover, the
      fractal dimensions were significantly higher for the elderly subjects than for
      the young subjects (p < 0.01). For the patients with Parkinson's disease, the
      fractal dimensions tended to be higher than those of healthy subjects. These
      results suggest that the acceleration signals change into a more complex pattern
      with aging and with Parkinson's disease, and the fractal dimension can be used to
      evaluate the gait of elderly subjects and patients with Parkinson's disease.

PMID- 12503785
TI  - Development of an indoor rowing machine with manual FES controller for total body
      exercise in paraplegia.
AB  - Concept 2 indoor rowing machine (Concept 2 Inc., USA) was modified for functional
      electrical stimulation (FES) rowing exercise in paraplegia. A new seating system
      provides trunk stability and constrains the leg motion to the sagittal plane. A 4
      channel electrical stimulator activates the quadriceps and hamstrings in Drive
      and Recovery phases of the rowing cycle, respectively. Two force-sensing
      resistors (FSR) on the handle measure the thumb press as the command signal to
      the electrical stimulator. Optical encoders measure the positions of the seat and
      handle during rowing. To synchronize the voluntarily controlled upper body
      movement with the FES controlled leg movement, a novel manual control system was
      developed. It uses the voluntary thumb presses to control the timing of the
      stimulation to the paralyzed leg muscles. The manual control system was intuitive
      and easy to learn and resulted in well-coordinated rowing. Evaluation of the
      modified rower by paraplegic volunteers showed that it is effective, safe, and
      affordable exercise alternative for paraplegics.

PMID- 12503786
TI  - A modified Perkins Brailler for text entry into windows applications.
AB  - In this paper, we describe how a Perkins Brailler can be adapted so that it can
      function as a keyboard to a personal computer. The paper describes the earlier
      work of others and the hardware and software of our system and concludes with
      indications of how the system may be improved.

PMID- 12503787
TI  - Role of the chemokine eotaxin in the pathogenesis of equine sweet itch.
AB  - The chemokine eotaxin is involved in the recruitment of eosinophils and T helper
      2 lymphocytes in human allergic diseases, and drugs that block its activity,
      including eotaxin receptor (CCR3) antagonists, are being developed. The authors
      have recently cloned the horse ortholog of eotaxin and shown that it can induce
      equine eosinophil migration and activation in vitro. Moreover, eotaxin mRNA
      expression was upregulated in cultured horse dermal fibroblasts exposed to equine
      interleukin-4, suggesting a possible source of this eosinophil chemoattractant in
      equine skin. The results of this study show that eotaxin and monocyte
      chemoattractant protein (MCP) 1, but not MCP-2 or MCP-4, mRNA expression is
      upregulated in skin biopsies of sweet itch lesions when eosinophils are present,
      when compared with clinically normal skin from the same ponies.

PMID- 12503788
TI  - Suspensory structures and supporting tissues of the third phalanx of cows and
      their relevance to the development of typical sole ulcers (Rusterholz ulcers).
AB  - The mural suspensory apparatus of third phalanx and its supportive heel cushion
      were examined in 19 cows with an ulcer at the 'typical' site (Rusterholz ulcer)
      to gain information on the pathogenesis of sole and heel ulcers. The claws of 17
      healthy controls were used for comparison. The left hind claws, frozen at -20
      degrees C, were sectioned in one longitudinal and four transverse planes with a
      band saw. The thickness of the subcutaneous tissue, the corium and the extent of
      displacement of the third phalanx were measured at defined sites on these
      sections. In addition, the suspensory apparatus, the tissue layer connecting the
      third phalanx to the dorsal wall of the horn capsule, was examined
      histologically. There was a direct relationship between the displacement of the
      third phalanx and ulceration of the sole or heel; in all the ulcerated claws the
      third phalanx had dropped and the corium and the subcutis under the bone were
      thinner than in the controls. The supportive cushions of the cows with ulcers
      contained less fat tissue. There was no histological evidence of damage to the
      epidermis or the corioepidermal junction in the ulcerated claws nor were the
      lamellae elongated. Similarly, there were no morphological changes in the
      connective tissue layer, the submural dermis.

PMID- 12503789
TI  - Outbreak of pneumonia and arthritis in beef calves associated with Mycoplasma
      bovis and Mycoplasma californicum.
AB  - During an outbreak of pneumonia and arthritis in beef calves and young cattle on
      a large farm in north-west Germany, Mycoplasma bovis and Mycoplasma californicum
      were isolated from tracheobronchial lavage fluids and synovial fluids. The
      microbiological findings in dead and living animals and the immunohistochemical
      demonstration of M californicum antigen in lung and arthritic joint tissue,
      indicated that under poor housing conditions and possibly other predisposing
      factors, this mycoplasma, like M bovis, can colonise the respiratory tract and
      may be able to cross the respiratory mucosal barrier to spread through an
      infected animal and cause systemic infections that may contribute to severe
      arthritis.

PMID- 12503790
TI  - Catastrophic mortality of flamingos in a Spanish national park caused by
      cyanobacteria.

PMID- 12503791
TI  - Accidental bromazepam intoxication in a dog.

PMID- 12503792
TI  - Toxoplasmosis in a western grey kangaroo in the UK.

PMID- 12503793
TI  - Mastitis and somatic cell counts.

PMID- 12503794
TI  - Prevalence of FeLV and antibodies to FIV and FCoV in Falkland Islands cats.

PMID- 12503795
TI  - Steroid-responsive meningitis-arteritis in the Nova Scotia duck tolling
      retriever.

PMID- 12503796
TI  - Equine borna disease in Japan.

PMID- 12503797
TI  - Medical virus.

PMID- 12503798
TI  - Long-term results after ankle arthrodesis: clinical, radiological, gait
      analytical aspects.
AB  - In a retrospective study the results of operatively treated ankle joints were
      critically discussed. In a period from January 1, 1977 to December 31, 1994, a
      total of 35 arthrodeses were carried out. Seventeen patients were followed up
      clinically, radiologically and with a gait analysis. Not only the radiological
      surgical result was of interest, but also the heel-toe movement of the stiffened
      foot in the individually adapted orthopedic footwear compared to standard
      footwear. A significantly improved heel-toe movement was found in orthopedic
      shoes, although there is a reduction of movement in the hindfoot in the sagittal
      plane.

PMID- 12503799
TI  - Treatment of post-traumatic ankle arthrosis with bipolar tibiotalar osteochondral
      shell allografts.
AB  - We report on tibiotalar osteochondral shell allografts for post-traumatic ankle
      arthropathy in seven patients. Average follow-up was 148 months (range, 85 to
      198). Patients were evaluated by a questionnaire, SF-12 survey, ankle score,
      physical exam and radiographs. The ankle score increased from 25 preoperatively
      to 43 at latest follow-up (maximum score 100). SF-12 scores increased from 30 to
      38 (Physical Component) and 46 to 53 (Mental Component). The failure rate was
      42%. Four of seven patients reported good or excellent results. Five patients
      stated they would undergo a similar procedure again. Complications included graft
      fragmentation, poor graft fit, graft subluxation, and non-union. Follow-up
      radiographs demonstrated joint space narrowing, osteophytes, and sclerosis, even
      in cases with excellent clinical status. Fresh osteochondral shell allografting
      may provide a viable alternative for the treatment of post-traumatic ankle
      arthrosis in selected individuals.

PMID- 12503800
TI  - Posterior tibial tendon transfer and tendo-Achilles lengthening for equinovarus
      foot deformity due to severe crush injury.
AB  - Surgical correction was performed on nine patients who had equinovarus deformity
      caused by severe crush injury of the leg sustained in an earthquake. The
      operative procedure used involved the transfer of the posterior tibial tendon to
      the dorsum of the foot by passing it through the interosseous membrane using a
      modified procedure as published in 1978. This procedure was combined with
      percutaneous Achilles tendon lengthening and tenotomy of toe flexors when needed.
      The average follow-up time after the operation was 21 months. The treatment
      improved the heel-toe steppage gait in all patients and all were able to walk in
      standard shoes. There were no complications in the postoperative period.
      Recurrence of varus deformity was not seen in any of the patients. They had
      active dorsiflexion of the foot, with a median active dorsiflexion of 5 degrees
      (0 to 10 degrees) and median active plantarflexion of 16.1 degrees (10 to 25
      degrees) compared to the median active dorsiflexion and plantarflexion on the
      uninvolved side. The total range-of-motion was 21.1 degrees (10 to 35 degrees).

PMID- 12503801
TI  - Intermediate term follow-up of calcaneal osteotomy and flexor digitorum longus
      transfer for treatment of posterior tibial tendon dysfunction.
AB  - Twenty-three patients with stage II posterior tibial tendon dysfunction who had
      failed non-surgical therapy were treated with flexor digitorum longus transfer
      and calcaneal osteotomy. At latest follow-up averaging 35 +/- 7 months (range, 24
      to 51 months), 22 patients (96%) were subjectively "better" or "much better." No
      patient had difficulty with shoe wear; however, four patients (17%) required
      routine orthotic use consisting of a molded shoe insert. AOFAS scores were
      available on 21 patients and improved from a preoperative mean of 50 +/- 14
      (range, 27 to 85) to a postoperative mean of 89 +/- 10 (range, 70 to 100). Our
      experience, at an intermediate date follow-up is that calcaneal osteotomy and
      flexor digitorum longus transfer is a safe and effective form of treatment for
      stage II posterior tibial tendon dysfunction.

PMID- 12503802
TI  - Redistribution of foot pressure in healthy adults during sideslope walking.
AB  - Normal adult plantar pressures were measured during both level and sideslope
      walking. Sideslope pressures increased, depending on the relative position of the
      foot on the slope. With upslope placement, pressures increased significantly at
      the midfoot (approximately 20%) and fifth metatarsal (approximately 16%). With
      downslope placement, pressure increased predominantly beneath the first
      metatarsal (approximately 11%). Pressure changes were relatively small at the
      heel (approximately 3%) and central metatarsals (approximately 4%). Significant
      increases occurred on sideslopes as small as 2 degrees. Since gradients of this
      size are likely to be encountered commonly in outdoor daily activities, this
      finding may have substantial implications for individuals with peripheral
      neuropathy.

PMID- 12503803
TI  - Toe flexor forces in dancers and non-dancers.
AB  - Toe flexor force (hallux and second toe) was determined in the right and left
      feet of 24 dancers and 29 non-dancers (sitting and standing positions) using a
      commercially-available pressure sensor connected to a voltmeter. For the hallux
      and second toe combined (all trials combined), average toe flexor force was
      slightly greater for dancers than non-dancers (dancers, 7 +/- 4 N; non-dancers, 6
      +/- 4 N; P<0.049). For dancers and non-dancers combined (all trials), the average
      toe flexor force of the hallux was more than twice that of the second toe
      (hallux, 9 +/- 4 N; 2nd toe, 4 +/- 1 N; P<0.0001); average toe flexor force was
      slightly greater in standing than sitting positions (standing, 7 +/- 4 N;
      sitting, 6 +/- 3 N; P<0.0001); and the average toe flexor force was slightly
      greater for the right than left foot (right, 7 +/- 4 N; left, 6 +/- 4 N;
      P<0.012). The average toe flexor force was greatest for the first repetition and
      slightly decreased for the second and third repetitions (first repetition, 7 +/-
      4 N; second and third repetitions each, 6 +/- 4 N; P<0.0013). Toe flexor force
      measurement may potentially be applicable to clinical practice as a guide to
      rehabilitation after injury or as a screening parameter for readiness to advance
      dance or other athletic training, performance, or competition.

PMID- 12503804
TI  - A new method of functional tendon transfer for the dysfunction of extensor
      hallucis longus.
AB  - A surgical technique of functional tendon transfer for the treatment of extensor
      hallucis longus (EHL) rupture is described. By using the extensor digitorum
      longus tendon of the second toe, the patient regains active dorsiflexion of the
      big toe and the deformity of the toe is corrected.

PMID- 12503805
TI  - Initial pull-out strength of tendon sutures: an in vitro study in sheep Achilles
      tendon.
AB  - Forty-eight fresh frozen sheep Achilles tendons were used to compare the pull-out
      strengths of Kessler, Bunnell and locking loop techniques which are the standard
      configurations described for Achilles tendon repair. A simulated Achilles tendon
      rupture was done with a tenotomy made 2 cm proximal to the calcaneal insertion.
      One of the configurations was placed at the distal end of the proximal portion of
      the tendon specimens using No. 5 Ticron. The distal ends of the suture materials
      were left free and were not used to connect the proximal and distal portions of
      the tendon. Using a servohydraulic materials testing machine, each tendon was
      tested to failure in tension at a displacement rate of 20 mm/min. All the
      specimens failed due to pull-out of the suture material. Since the cause of
      failure was suture material breakage in the previous studies reporting repair
      strength, they were unable to represent the effect of configuration on the
      strength. This study is the first to represent the effect of configuration on the
      initial strength since there is no failure due to suture material breakage.

PMID- 12503806
TI  - Tuberculous tenosynovitis of the tibialis anterior tendon: a case report.
AB  - Tuberculous tenosynovitis is an uncommon form of extrapulmonary tuberculosis
      occurring primarily in the hands and wrists with limited reports involving the
      lower extremities. We report a rare case of tuberculous tenosynovitis of the
      tibialis anterior tendon occurring in a 37-year-old Filipino male. The tendon was
      surgically debrided and the patient was given a six month course of
      antituberculin chemotherapy. At one year postoperatively, the patient has good
      function with no evidence of recurrence.

PMID- 12503807
TI  - Chronic subtalar instability due to insufficiency of the calcaneofibular
      ligament: a case report.
AB  - Calcaneofibular ligament insufficiency in isolation is an uncommon cause of
      chronic instability of the subtalar joint. We report one case of chronic subtalar
      instability due to calcaneofibular ligament insufficiency after an ankle sprain.
      It was diagnosed with clinical findings and stress radiograph, and successfully
      treated with proximal advancement of the elongated calcaneofibular ligament.

PMID- 12503808
TI  - Modified split extensor hallucis longus tendon transfer for correction of hallux
      varus.

PMID- 12503809
TI  - Percutaneous release of deltoid ligament entrapment.

PMID- 12503810
TI  - A risky business.

PMID- 12503811
TI  - Use of complementary alternative medicine in patients admitted to internal
      medicine wards.
AB  - OBJECTIVE: To evaluate rate and type of complementary alternative medicine (CAM)
      use in patients admitted to a medical ward. To identify demographic and disease
      or treatment-related factors associated with CAM use in these patients. To
      evaluate the awareness of physicians regarding this practice and whether CAM use
      had contributed to hospital admission. METHODS: This study is based on
      consecutive interviews and chart reviews of 180 patients admitted to the
      Department of Internal Medicine, Hadassah Hebrew University Hospital in
      Jerusalem, Israel. 29 patients were excluded due to impaired cognitive state and
      2 patients refused to participate in the study. Patients were asked questions
      concerning sociodemographic characteristics and CAM use: type, time, duration of
      use, causes, outcomes and communication about CAM use with their hospital and
      family physicians. Information about background diseases, acute diagnoses that
      led to hospitalization, symptoms on admission, drugs taken at home prior to
      admission was provided by chart reviews. RESULTS: 26% of patients reported a
      lifetime history of CAM use and 11% during the month prior to admission. Younger
      age, higher education and Israeli, USA or European origin was associated with
      more frequent CAM use. Hospital physicians were informed only about 12% of the
      CAM courses in the month prior to admission, whereas family physicians were aware
      of about half of them. No direct or indirect harmful effects of CAM were noticed
      in this study. No essential changes in the regimen of drugs or other conventional
      treatments due to CAM use were found. If the condition deteriorated, patients did
      not defer their visit to hospital because of CAM use. CONCLUSIONS: With
      reservations due to small sample size, it appears that CAM use was not an
      important factor influencing hospital admissions to a medical ward. Awareness of
      the hospital physicians regarding CAM use in their patients during the month
      prior to admission was much lower than that of the family physicians (12% vs.
      51.3%).

PMID- 12503812
TI  - Determination of the acetylator phenotype in Moroccan tuberculosis patients using
      isoniazid as metabolic probe.
AB  - A large interindividual variability in drug acetylation is associated with
      genetic polymorphism of the polymorphic Type 2 N-acetyltransferase (NAT2), and an
      important interethnic difference has been frequently observed. However, few data
      on this polymorphism in the Moroccan population are available. In the present
      study the acetylator phenotype in 89 Moroccan patients with tuberculosis has been
      determined using isoniazid (INH) as metabolic probe. The subjects (69 women and
      20 men between 18 and 77) were each given a 5 mg/kg oral dose of INH. Plasma
      concentration of INH and its metabolite, acetylisoniazid (ac.INH), were measured
      by high-performance liquid chromatography at 3 hours post dose. The plasma level
      ratio of acetylisoniazid to isoniazid (Rm), and the plasma level of
      acetylisoniazid as a percentage (%ac.INH) were used to express the activity of
      the polymorphic NAT2. The distribution of these 2 parameters in the studied
      population was clearly bimodal resulting in 2 distinct groups: slow acetylators
      (Rm < or = 0.84, %ac.INH < or = 45.64%), and fast acetylators (Rm > or = 1.29,
      %ac.INH > or = 56.26%) who accounted respectively for 61.8% and 38.2% of the
      population. The 2 approaches used showed a complete concordance.

PMID- 12503813
TI  - Simultaneous quantification of citalopram, clozapine, fluoxetine, norfluoxetine,
      maprotiline, desmethylmaprotiline and trazodone in human serum by HPLC analysis.
AB  - We describe an analytical procedure for the simultaneous quantification of
      citalopram (seropram), clozapine (leponex), fluoxetine (fluctine), norfluoxetine,
      maprotiline (ludiomil), desmethylmaprotiline and trazodone (trittico) in human
      serum within a period of 11.5 minutes using reversed phase HPLC. After 2
      liquid/liquid extractions in the sample preparation phase, the drugs and
      metabolites were separated on a C18 column using a mobile phase consisting of
      acetonitrile/buffer (30/70, v:v) at 70 degrees C, a flow rate of 1.5 m/min and
      haloperidol as internal standard. Absorption and native fluorescence signals of
      the eluted compounds were detected simultaneously at 260 nm and 227/300 nm
      (excitation/emission), respectively. The calibration ranges for citalopram,
      clozapine, fluoxetine, norfluoxetine, maprotiline, and desmethylmaprotiline
      ranged from 50-400 microg/l and for trazodone from 50-3,200 microg/l. The CVs
      varied between 0.6% and 5.5% (within-run) and between 3.2% and 7.1% (between
      run). Recoveries were > 90% for all pharmaceuticals. We noticed no interferences
      from several commonly used drugs.

PMID- 12503814
TI  - Molecular-epidemiological aspects of carcinogenesis: the role of xenobiotic
      metabolizing enzymes.

PMID- 12503815
TI  - Aminopterin-human serum albumin conjugate (AP-HSA): uptake and cytotoxic effects
      in tumor cell lines.

PMID- 12503816
TI  - ERK1/2 phosphorylation: a biomarker analysis within a phase I study with the new
      Raf kinase inhibitor BAY43-9006.

PMID- 12503817
TI  - Interindividual differences in oxaliplatin pharmacokinetics.

PMID- 12503818
TI  - Penetration of capecitabine and its metabolites into malignant and healthy tissue
      of patients with advanced breast cancer.

PMID- 12503819
TI  - Serial measurements of pharmacokinetics, DCE-MRI, blood flow, PET and biomarkers
      in serum/plasma--what is a useful tool in clinical studies of anti-angiogenic
      drugs?

PMID- 12503820
TI  - The influence of elevated liver function parameters on the pharmacokinetics of
      doxorubicin and epirubicin--a population based pharmacokinetic study of CESAR
      APOH. Central European Society for Anticancer Drug Research. Working Group for
      Pharmacology in Oncology and Hematology.

PMID- 12503821
TI  - Population pharmacokinetics of etoposide.

PMID- 12503822
TI  - Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase
      inhibitor BAY 43-9006 in patients with solid tumors.

PMID- 12503823
TI  - Monitoring of methotrexate and reduced folates in the cerebrospinal fluid of
      cancer patients.

PMID- 12503824
TI  - Serum HER-2/neu: a new predictive marker.

PMID- 12503825
TI  - Population pharmacokinetics of cyclophosphamide, doxorubicin and etoposide in 30
      patients with BEACOPP chemotherapy.

PMID- 12503826
TI  - Gender differences in proenkephalin gene expression response to delta9
      tetrahydrocannabinol in the hypothalamus of the rat.
AB  - Chronic exposure to delta9-tetrahydrocannabinol (delta9-THC) produces an
      activation of preproenkephalin (PENK) gene expression in the rat hypothalamus.
      The levels of circulating gonadal steroids concurrently modulate this
      neuropeptide in male and female rats. However, whether gonadal steroids regulate
      delta9-THC effects on PENK gene expression in the hypothalamus of male and female
      rats remains unknown. To test this hypothesis, experiments were carried out on
      intact, 2-week-gonadectomized, 1-week-gonadectomized, 1-week-dihydrotestosterone
      (DHT) replaced male rats, and 2-week-gonadectomized, 1-week-gonadectomized, 1
      week-oestradiol replaced female rats. One week after hormonal replacement,
      animals were treated with vehicle or delta9-THC (5 mg/kg/day, i.p. 7 days). In
      males, delta9-THC administration to intact animals induced PENK mRNA in the
      paraventricular nucleus (PVN) and ventromedial nucleus (VMN) of the hypothalamus.
      Orchidectomy did not affect basal PENK mRNA levels in the PVN, but reduced PENK
      mRNA levels in the VMN. However, delta9-THC treatment induced PENK gene
      expression to the same extent in both hypothalamic nuclei of intact, castrated
      and DHT-replaced males. In females, ovariectomy decreased PENK gene expression in
      PVN and VMN. delta9-THC administration increased PENK gene expression in
      castrated females, but had no effect in the oestradiol-replaced group. Taken
      together, these results suggest gender differences in the response of chronic
      exposure to cannabinoids on PENK gene expression in the hypothalamus.
      Furthermore, it appears that alterations in opioid gene expression induced by
      cannabinoids in female rats depend upon the presence or absence of circulating
      oestradiol.

PMID- 12503827
TI  - Characterization of olanzapine-induced weight gain in rats.
AB  - Novel antipsychotic drugs (APDs) have enhanced therapeutic actions compared to
      'typical' APDs. However, clinical studies indicate that some induce marked weight
      gain. We attempted to model this effect in female Wistar rats given olanzapine
      chronically at 4 mg/kg b.i.d (4.5 h between injections). Such rats showed marked
      weight gain, which was statistically significant after only a single day of
      treatment, although weight gain increased up to a plateau after 10 days of
      treatment. Cessation of treatment led to rapid weight loss, which was significant
      after a single day of withdrawal. The weight gain observed was characterized by
      marked individual differences. As some clinical reports suggest that novel APD
      induced weight gain is most pronounced in patients with the lowest body weight,
      we examined the relationship between weight gain and baseline body weight.
      However, we observed no significant relationship between baseline body weight and
      weight gain. The observation that olanzapine can induce weight gain rapidly in
      rats, in conjunction with the observation of marked individual differences in
      weight gain, suggests that patients at risk of developing weight gain might be
      detectable early in treatment. Furthermore, the finding that weight gain is
      rapidly reversible suggests that patients at risk of weight gain could be
      switched to APDs with less pronounced tendencies to induce weight gain. The study
      of APD-induced weight gain in rodents may provide insights into the nature,
      causes, and treatments for, novel APD-induced weight gain in the clinic. However,
      it remains to be determined how closely rodent models mimic the clinical
      situation and whether the mechanism(s) involved in the weight gain we have
      observed are the same as those involved in the clinical use of these drugs.

PMID- 12503828
TI  - Comparison of the effects of antidepressants on norepinephrine and serotonin
      concentrations in the rat frontal cortex: an in-vivo microdialysis study.
AB  - The present study employed in-vivo microdialysis techniques in the freely moving
      rat to systematically compare the neurochemical effects of various antidepressant
      agents on extracellular concentrations of norepinephrine (NE) and serotonin (5
      HT) in the frontal cortex. We found that acute administration of the tricyclic
      antidepressant, desipramine (3-30 mg/kg, s.c.) and the dual
      serotonin/norepinephrine reuptake inhibitor, venlafaxine (3-30 mg/kg, s.c.),
      produced dose-dependent and robust increases in cortical NE concentrations (498%
      and 403%, respectively). Conversely, acute injection of the selective serotonin
      reuptake inhibitors, fluoxetine (30 mg/kg, s.c.) and paroxetine (1-10 mg/kg,
      s.c.), did not alter forebrain NE concentrations. However, paroxetine did produce
      a significant increase in cortical NE concentrations (164%) when administered at
      30 mg/kg. These changes in NE were not paralleled by 5-HT, which showed no
      increase following administration of desipramine, venlafaxine, paroxetine or
      fluoxetine. Combination treatment with the 5-HT1A receptor antagonist, WAY-100635
      (0.3 mg/kg, s.c.), significantly enhanced extracellular 5-HT concentrations
      following venlafaxine (10 and 30 mg/kg), fluoxetine (30 mg/kg) and paroxetine (3
      30 mg/kg). Alternatively, WAY-100635 produced no augmentation of the
      antidepressant-induced changes in extracellular NE. Collectively, these studies
      show that paroxetine, at low to intermediate doses, and fluoxetine are selective
      for 5-HT versus NE systems, whereas venlafaxine produces similar effects on both
      5-HT and NE levels at the effective doses tested.

PMID- 12503829
TI  - Opposite effects of ethanol and ketamine in the elevated plus-maze test in Wistar
      rats undergoing a chronic oral voluntary consumption procedure.
AB  - The anxiolytic effects of ethanol (EtOH) have been involved in the vulnerability
      to EtOH drinking in humans. However, the role of the anxiolytic effects of EtOH
      during a chronic ingestion of the drug has not been extensively addressed, either
      in humans or in animal models. Since it was first shown that EtOH interacts with
      the N-methyl-d-aspartate (NMDA) receptor, a growing body of evidence
      demonstrating the involvement of this receptor in a wide range of EtOH effects
      has been reported. The present study aimed to investigate the ability of a
      voluntary consumption of EtOH to exert its putative anxiolytic-like activity in
      non-selected male Wistar rats held under a voluntary chronic oral consumption
      procedure using the elevated plus-maze (EPM) test. The effects of EtOH were
      compared with those of the noncompetitive NMDA receptor antagonist ketamine
      (KET), and with a mixture of both drugs. Rats were provided with 1-h limited
      access to one of the following sweetened (10% w/v glucose) solutions: (i)
      control; (ii) EtOH (ethanol, 10% v/v); (iii) KET (ketamine HCl, 0.28 mg/ml); or
      (iv) mixed (EtOH 10% v/v plus ketamine HCl 0.28 mg/ml) for 35 consecutive days.
      At the end of this period, and immediately after the last 1-h access to the
      respective solution, animals were independently tested in either EPM or open
      field tests. Previously, rats were tested on the inclined screen test during 15
      consecutive days. The opposite effects were observed with EtOH and KET
      consumption in the EPM test, with EtOH decreasing and KET increasing the
      percentage of time spent in the open arms of the EPM, which was shown to be
      independent of any locomotor impairment, whereas consumption of the mixed
      solution did not significantly affect any test. Since the EtOH did not exhibit
      anxiolytic-like effects after its chronic oral consumption, it might be
      hypothesized that the anxiolytic activity of the EtOH is not critically involved
      in the maintenance of a voluntary EtOH consumption in non-selected rats. On the
      other hand, the lack of effects from mixed solution consumption suggests that
      EtOH and KET may interact in such a way that their effects are neutralized.

PMID- 12503830
TI  - Effects of intrahippocampal injection of GABAergic drugs on memory retention of
      passive avoidance learning in rats.
AB  - The effect of post-training intrahippocampal injection of gamma-aminobutyric acid
      (GABA) receptor agonists and antagonists, immediately after a training session on
      memory retention of passive avoidance learning in rats, was measured in the
      presence and absence of physostigmine. Post-training treatments were carried out
      in all the experiments. The different doses of the GABAA receptor agonist
      muscimol (2, 4 and 6 microg/rat) decreased memory retention in rats dose
      dependently. The higher response was obtained with 6 microg/rat of the drug. When
      the GABAA receptor antagonist bicuculline (0.5, 1, 2 and 4 microg/rat) was
      administered, only one dose of the drug (1 microg/rat) increased memory
      retention; however, the antagonist reduced the effect of muscimol. The GABAB
      receptor agonist, baclofen (0.25, 0.5, 1 and 2 microg/rat) also reduced memory
      retention in the animals. Intrahippocampal injection of lower doses of the GABAB
      receptor antagonist CGP35348 (P-[3-aminopropyl]-p-diethoxymethyl-phosphinic acid)
      (2.5, 5, 10 microg/rat) did not effect memory retention, although the higher
      doses of the drug (25 and 50 microg/rat) decreased memory retention. The doses of
      antagonist (2.5, 5 and 10 microg/rat), which did not elicit any response alone,
      reduced the effect of baclofen. The inhibitory response of CGP35348 was also
      decreased by bicuculline. In another series of experiments, physostigmine
      improved memory retention. The GABA receptor agonists, muscimol and baclofen, as
      well as the GABA receptor antagonists bicuculline and CGP35348, decreased the
      effect of physostigmine. Atropine decreased memory retention by itself and
      potentiated the response of muscimol and baclofen. It is concluded that GABAA and
      GABAB receptor activation may be involved in the impairment of memory retention.

PMID- 12503831
TI  - Effects of 5 weeks of administration of fluoxetine and dothiepin in normal
      volunteers on sleep, daytime sedation, psychomotor performance and mood.
AB  - This was a placebo-controlled, double-blind randomized crossover study of long
      term (5 weeks) administration of fluoxetine (20 mg/day) and dothiepin (75 mg/day
      for 1 week followed by 150 mg/day for 4 weeks) in 12 healthy male volunteers.
      Subjects were studied on day 10 and day 36 of treatment, with tests of nocturnal
      sleep, driving performance, continuous electroencephalogram (EEG), sleep during
      scheduled naps, computerized visual attention tasks, saccadic eye movement
      measurement and visual analogue ratings of mood. Both drugs had a marked
      suppressive effect on nocturnal rapid eye movement (REM) sleep; these effects
      were less at 36 days than at 10 days, and fluoxetine decreased and dothiepin
      increased REM in daytime naps. Sleep fragmentation after fluoxetine is similar to
      that reported in the literature. We found no sleep-promoting effects of
      dothiepin, in contrast to our previous single-dose study, and no subjective sleep
      effects of either drug. Subjects were less sleepy after both antidepressants than
      placebo at 5 weeks measured by sleep latencies and EEG. Saccadic eye movement
      measures were significantly faster after 5 weeks of fluoxetine than after 5 weeks
      of placebo. Reaction times to a peripheral stimulus during computerized tracking
      task were shorter after 10 days of dothiepin compared with placebo. Driving
      performance, visual attention and mood ratings showed no treatment effects.
      Subjective health reports during each 5 weeks of treatment were similar in number
      for the two drugs but showed a different profile of side-effects.

PMID- 12503832
TI  - The effects of reboxetine, a noradrenaline reuptake inhibitor, on the plasma
      noradrenaline response to a cold pressor test in healthy volunteers.
AB  - Previous studies have shown peripheral abnormalities in noradrenergic activity in
      depressed melancholic patients. These abnormalities have a relationship with
      short-term and long-term outcome. Little is known about the effects of
      antidepressant treatment on these peripheral measures such as plasma
      noradrenaline (NA) and the plasma NA response to a laboratory stressor, the cold
      pressor test (CPT). The present study examines the effects of the antidepressant
      reboxetine, a noradrenaline reuptake inhibitor, on baseline plasma NA and the
      plasma NA response to a CPT, in nine healthy volunteers compared to placebo. A
      double-blind crossover design was used, with each agent given for 4 weeks with a
      4-week washout period. There was no effect of reboxetine on baseline plasma NA.
      The plasma NA response to reboxetine, with a CPT, was blunted 3 days after
      commencing treatment. Reboxetine alters the plasma NA response to a CPT
      independent of baseline plasma NA.

PMID- 12503833
TI  - Evaluation of tests of central nervous system performance after hypoxemia for a
      model for cognitive impairment.
AB  - The sensitivity of several neurophysiological and cognitive tests to different
      levels of hypoxia was investigated. Cerebral hypoxia in healthy volunteers may be
      a disease model for dementia or other forms of brain dysfunction. Twelve healthy
      subjects were included in a randomized, single-blind, placebo-controlled, three
      period cross-over trial. They received three air/N2 gas mixtures via mask
      breathing [aimed at peripheral oxygen saturation (SPO2) values of > 97%
      (placebo), 90% and 80%, with normal end-tidal CO2]. Central nervous system
      effects were tested regularly for 130 min by saccadic and smooth pursuit eye
      movements, electro-encephalogram, visual analogue scales and cognitive tests.
      Treatments were well tolerated. Compared to SPO2 90%, SPO2 80% reduced saccadic
      peak velocity by 16.4 degrees/s [confidence interval (CI) -26.3, -6.4], increased
      occipital delta power by 14.3% (CI 3.6, 25.1), and significantly increased most
      cognitive reaction times. SPO2 80% also decreased correct responses for the
      binary choice task and serial word recognition [-1.3 (-2.2, -0.3) and -3.5 (-6.2,
      -0.8), respectively] compared to SPO2 90%. Cognitive performance was decreased by
      SPO2 80% and increased by SPO2 90% compared to placebo. Sensitive effect
      measurements can be identified for these interventions. The applicability as a
      model for cognitive impairment should be investigated further.

PMID- 12503834
TI  - The effects of single-dose lorazepam on memory and behavioural learning.
AB  - To assess the influence of lorazepam on memory and behavioural learning, a non
      clinical sample of undergraduate psychology students (n = 24), received lorazepam
      (2.5 mg) or placebo orally. Pre-drug and post-drug neuropsychological assessment
      comprised the Rey auditory verbal learning test, verbal fluency test, digit span
      and word stem completion. Relative to placebo, lorazepam induced a marked deficit
      in delayed free-recall, perceptual priming, and written word fluency, with
      preservation of digit span. Behavioural learning was assessed on a computer-aided
      vicarious exposure treatment for obsessive-compulsive disorder, administered post
      drug, and repeated 1 week later, drug free. Compared to placebo, lorazepam
      treated participants enacted 51% less exposure activity on the behavioural
      learning task post-drug. Whilst both groups enacted increased exposure at the
      drug-free session, exposure activity was 49% less in the lorazepam group,
      indicating a carryover effect of the impaired learning under drug 1 week before.
      There were no significant differences between lorazepam and placebo on indices of
      overall activity on the program. These results suggest lorazepam-induced
      impairment in the ability to learn behavioural strategies, possibly due to
      impaired acquisition of information into long-term episodic memory. These
      findings suggest caution in the co-prescribing of benzodiazepines in people
      undergoing behavioural therapies in clinical populations.

PMID- 12503835
TI  - The potential cardiotoxicity of antipsychotic drugs as assessed by heart rate
      variability.
AB  - Most antipsychotic drugs have cardiac effects as a consequence of their
      pharmacological actions. Recently, thioridazine has been subjected to a
      restricted indications notice and sertindole had its license withdrawn because of
      concerns about their potential cardiotoxicity. In the development of new atypical
      agents, heart-rate corrected QT effects are evaluated but it is unclear how
      predictive these are of clinically significant cardiotoxicity or sudden death.
      Heart rate variability (HRV) is a potential index of cardiotoxicity which has
      been found to be decreased following antidepressants and clozapine. We studied
      acute HRV changes following antipsychotic agents. Sixteen healthy male volunteers
      received risperidone (4 mg), olanzapine (10 mg), thioridazine (50 mg) or placebo
      in a randomized cross-over design. Subjective effects and psychomotor function
      were assayed at 2 h and both linear (summary statistics) and non-linear
      (scatterplot) measures of HRV were evaluated by continuous electrocardiogram
      recording over 10 h. Differential effects of single doses of the three
      antipsychotic drugs on HRV were found, and these were independent of their
      sedative effects. Olanzapine increased, and thioridazine decreased HRV, while
      risperidone had no effect. HRV is sensitive to the acute effects of
      antipsychotics. It may prove to be a reliable index of their potential for
      cardiotoxicity. Further studies in both healthy volunteers and patients on
      antipsychotic medication will be valuable.

PMID- 12503836
TI  - QTc interval lengthening is related to CYP2D6 hydroxylation capacity and plasma
      concentration of thioridazine in patients.
AB  - Thioridazine cardiotoxicity has been associated with a prolonged heart-rate
      corrected QT (QTc) interval. However, no systematic studies have been performed
      on patients at therapeutic doses. The present study aimed to evaluate the
      influence of dose and plasma concentration of thioridazine and CYP2D6 enzyme
      status on the QTc interval in psychiatric patients. Sixty-five Spanish European
      psychiatric patients receiving thioridazine antipsychotic monotherapy were
      studied. The plasma levels of thioridazine and its metabolites were determined by
      high-performance liquid chromatography. All patients were phenotyped for CYP2D6
      activity with debrisoquine during treatment. Thirty-five patients (54%) had a QTc
      interval over 420 ms. The lengthening of QTc interval was correlated with plasma
      concentration (p < 0.05) and daily dose (p < 0.05) of thioridazine. CYP2D6 enzyme
      hydroxylation capacity, evaluated by debrisoquine metabolic ratio (MR) (p < 0.05)
      and thioridazine/mesoridazine ratio (p < 0.05), was also correlated with QTc
      intervals. The present study shows the relationship between QTc interval
      lengthening among psychiatric patients treated at therapeutical doses with the
      dose and the plasma concentration of thioridazine. Since debrisoquine MR has been
      shown to be correlated with the QTc intervals, CYP2D6 enzyme hydroxylation
      capacity might be relevant in determining the risk for QTc interval lengthening.
      Patients with impaired CYP2D6 enzyme activity due to enzyme inhibition by
      thioridazine might be more prone to increased risk of sudden death due to torsade
      de pointes type cardiac dysrhythmia.

PMID- 12503837
TI  - Efficacy of olanzapine in social anxiety disorder: a pilot study.
AB  - Based on evidence suggesting anxiolytic properties of the atypical antipsychotic
      olanzapine, this study was conducted to evaluate whether olanzapine may be
      efficacious in treating social anxiety disorder (SAD). This study was an 8-week,
      double-blind, placebo-controlled evaluation of olanzapine as monotherapy in which
      12 patients with the DSM-IV diagnosis of SAD were randomized to either olanzapine
      (n = 7) or placebo (n = 5). An initial dose of 5 mg/day was titrated to a maximum
      of 20 mg/day. Baseline to endpoint scores from the Brief Social Phobia Scale
      (BSPS), Social Phobia Inventory (SPIN), Liebowitz Social Anxiety Scale and
      Sheehan Disability Scale, as well as Clinical Global Impression-Improvement
      ratings, were compared for olanzapine versus placebo. Seven subjects completed
      all 8 weeks of the study, four in the olanzapine group and three in the placebo
      group. In the intent-to-treat analysis, olanzapine yielded greater improvement
      than placebo on the primary measures: BSPS (p = 0.02) and SPIN (p = 0.01). Both
      treatments were well tolerated, although the olanzapine group had more drowsiness
      and dry mouth. Olanzapine and placebo were both associated with negligible weight
      gain. Olanzapine was superior to placebo on the primary outcome measures in this
      preliminary study of SAD. Additional studies of olanzapine as a treatment for SAD
      are warranted.

PMID- 12503838
TI  - Venlafaxine: the relationship between dose, plasma concentration and clinical
      response in depressive patients.
AB  - The relationship between plasma drug level of venlafaxine and daily intake was
      studied in 89 major depressive inpatients. In addition, changes over time in
      severity were assessed weekly in a subgroup of 22 depressed patients using the
      Montgomery and Asberg Depression Rating Scale (MADRS) and the Clinical Global
      Impression improvement scale. The results indicate a moderate correlation between
      daily doses and plasma concentrations, together with a higher relationship
      between improvement on the MADRS scale and concentration. Moreover, plasma
      concentrations (for venlafaxine and its predominant metabolite, O
      desmethylvenlafaxine) up to 400 microg/l can be considered as effective, as
      already suggested in a previous study. No case of venlafaxine discontinuation
      occurred during the longitudinal study, and the incidence of adverse event, as
      estimated by the Target Emergent Symptoms and Side-effects scale, was low,
      suggesting that the drug is well tolerated for such plasma concentrations.

PMID- 12503839
TI  - The prescription of dexamphetamine to patients with schizophrenia and amphetamine
      dependence.
AB  - Patients with a severe mental illness such as schizophrenia have significant
      rates of concurrent amphetamine use. Such dual diagnosis patients have been shown
      to have poorer treatment outcomes. Often, they do not comply with treatment plans
      and have frequent episodes of hospitalization. There is growing evidence for the
      role of prescribed dexamphetamine in the treatment of amphetamine dependence. The
      prescription of dexamphetamine to patients with schizophrenia and amphetamine
      dependence has not been previously reported. Eight schizophrenic patients are
      described to whom dexamphetamine has been prescribed, with information being
      extracted retrospectively from case notes. In four out of eight cases, the
      prescription of dexamphetamine led to apparently good progress both in terms of
      substance misuse and psychiatric health. In two cases, progress was more
      equivocal, but appeared to produce some benefit. Two cases could be judged as
      treatment failures, but the condition and situation of the patients were not
      worse at the end of treatment than at the beginning. Compliance with neuroleptics
      increased in most cases. No patients exhibited exacerbation of psychosis as a
      result of treatment. The rate of outcome success is satisfactory when
      consideration is given to the difficult nature of this patient group, and their
      previous failure to respond to intensive treatment. It is argued that benefits
      may be gained from increased compliance with psychiatric treatment in patients
      prescribed amphetamine, and that this may outweigh possible risks. However, any
      conclusions are tentative in view of the nature of this study. A small open-label
      prospective study is recommended.

PMID- 12503840
TI  - Effect of ethanol on psychomotor performance and on risk taking behaviour.
AB  - Ethanol may increase the willingness to take risks, but this issue remains
      controversial. We used a risk-taking paradigm in which volunteers answered a
      series of general knowledge questions with numerical answers and were asked to
      judge the length of a line that would just fit into a given gap. A maximum score
      was given for an exactly correct answer. For answers that were less than the
      correct value, the score was reduced gradually to zero, while answers even
      slightly over the correct value were penalized considerably. Total points were
      rewarded by cash payments, so volunteers were taking real risks when making their
      responses. Performance was assessed in a two-period, double-blind crossover
      study, comparing ethanol (0.7 g/kg) with placebo in 20 female volunteers aged 19
      20 years. Tests were carried out before and at 45 min after dosing. Mean (SD)
      ethanol blood alcohol concentrations were 65 (10.5) mg/100 ml. Ethanol impaired
      the skill/ability measure of the length estimation test (SD of difference between
      length of line and gap), which increased from 5.9 to 6.6 (p < 0.05), indicating a
      reduced accuracy of estimation. The risk measures in both tasks were not
      significantly affected. The skill/ability measure in the general knowledge task
      was not significantly affected. Other performance tests showed that ethanol
      produced the expected impairment of both speed and accuracy. These results
      suggest that risk-taking is not increased by ethanol at doses approaching the UK
      legal limit for driving.

PMID- 12503841
TI  - Selective processing of smoking-related cues in smokers: manipulation of
      deprivation level and comparison of three measures of processing bias.
AB  - Recent theories of addiction suggest that an attentional bias for drug-related
      cues plays an important role in maintaining drug-taking behaviours. A key feature
      of the present study is that it used three different measures of processing bias
      for linguistic and pictorial smoking-related cues: masked and unmasked conditions
      of the modified Stroop task, and a pictorial version of the visual probe task.
      Participants were smokers (n = 27), who were tested twice, with deprivation level
      manipulated as a within-subjects variable. They were asked to abstain from
      smoking for 12 h before one session, and to smoke normally before the other.
      Results were consistent with an attentional bias for smoking-related pictures on
      the visual probe task, and for smoking-related words in the unmasked condition of
      the modified Stroop task. The latter bias was most strongly predicted by self
      reported urge to smoke, rather than by the deprivation manipulation. There was no
      evidence of a preconscious bias for smoking cues. The three measures of cognitive
      bias (from masked and unmasked Stroop and visual probe tasks) were not
      significantly correlated with each other, which suggests they may tap different
      underlying mechanisms. We discuss the results with respect to conceptualizations
      of selective attention, addiction and motivational states in general.

PMID- 12503842
TI  - Maintained improvement with minocycline of a patient with advanced Huntington's
      disease.
AB  - We present the case of a patient with advanced Huntington's disease treated with
      minocycline. Minocycline (but not tetracycline which does not cross the blood
      brain barrier) appears to increase longevity in an animal model for Huntington's
      disease. The patient has been maintained on minocycline for more than 1 year with
      positive effects. Cessation of minocyclin for 3 weeks resulted in an exacerbation
      of symptoms. The animal studies have suggested that minocycline may prevent
      progression of Huntington's disease and other neurological disorders. By
      contrast, this present result suggests that minocycline may benefit those with
      advanced Huntington's disease and can be used safely in these patients.

PMID- 12503843
TI  - Acute dystonic reaction in an elderly patient with mood disorder after titration
      of paroxetine: possible mechanisms and implications for clinical care.
AB  - The administration of a serotonin reuptake inhibitor may lead to extra pyramidal
      signs, as reported in the literature. The risk seems to be increased in elderly
      people. We describe a case of acute dystonic reaction to paroxetine treatment in
      an elderly patient, who presented with a bipolar affective disorder. The
      underlying mechanism, possibly generated in the subcortical motor areas, is
      linked to changes that occur in the pharmacokinetic variables, the decreased
      neuroplasticity of ageing neurones and to previous exposure to neuroleptic
      medications.

PMID- 12503844
TI  - The development of a clinical syndrome of asymptomatic pancreatitis and
      eosinophilia after treatment with clozapine in schizophrenia: implications for
      clinical care, recognition and management.
AB  - Clozapine, the first atypical antipsychotic, is indicated for the treatment of
      therapy-resistant schizophrenia. It needs to be monitored closely because of its
      well-known potential side-effects, especially agranulocytosis. We present a case
      of a middle-aged woman with chronic schizophrenia, who was treated with clozapine
      and developed a clinical syndrome of asymptomatic pancreatitis and eosinophilia
      within the fifth week of treatment. Asymptomatic pancreatitis has rarely been
      reported up to now and is not recognized as a typical side-effect of clozapine.
      In our opinion, pancreatic enzymes should be monitored especially in the first 6
      weeks of clozapine treatment.

PMID- 12503845
TI  - Possible serotonin syndrome after combination of buspirone and St John's Wort.

PMID- 12503846
TI  - Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells.
AB  - This article concerns the localization of glucocorticoid and thyroid hormone
      receptors in mitochondria of animal cells. The receptors are discussed in terms
      of their potential role in the regulation of mitochondrial transcription and
      energy production by the oxidative phosphorylation pathway, realized both by
      nuclear-encoded and mitochondrially encoded enzymes. A brief survey of the role
      of glucocorticoid and thyroid hormones on energy metabolism is presented,
      followed by a description of the molecular mode of action of these hormones and
      of the central role of the receptors in regulation of transcription.
      Subsequently, the structure and characteristics of glucocorticoid and thyroid
      hormone receptors are described, followed by a section on the effects of
      glucocorticoid and thyroid hormones on the transcription of mitochondrial and
      nuclear genes encoding subunits of OXPHOS and by an introduction to the
      mitochondrial genome and its transcription. A comprehensive description of the
      data demonstrates the localization of glucocorticoid and thyroid hormone
      receptors in mitochondria as well as the detection of potential hormone response
      elements that bind to these receptors. This leads to the conclusion that the
      receptors potentially play a role in the regulation of transcription of
      mitochondrial genes. The in organello mitochondrial system, which is capable of
      sustaining transcription in the absence of nuclear participation, is presented,
      responding to T3 with increased transcription rates, and the central role of a
      thyroid receptor isoform in the transcription effect is emphasized. Lastly,
      possible ways of coordinating nuclear and mitochondrial gene transcription in
      response to glucocorticoid and thyroid hormones are discussed, the hormones
      acting directly on the genes of the two compartments by way of common hormone
      response elements and indirectly on mitochondrial genes by stimulation of nuclear
      encoded transcription factors.

PMID- 12503847
TI  - Plastid division: its origins and evolution.
AB  - Photosynthetic eukaryotes have evolved plastid division mechanisms since
      acquisition of plastids through endosymbiosis. The emerging evolutionary origin
      of the plastid division mechanism is remarkably complex. The constituents of the
      division apparatus of plastids may have complex origins. The one constituent is
      the plastid FtsZ ring taken over from the cyanobacteria-like ancestral
      endosymbionts. The second is the doublet of concentric plastid dividing rings (or
      triplet in red algae), possibly acquired by ancestral host eukaryotes following
      the primary endosymbiotic event. Placement of the division apparatus at the
      correct division site may involve a system analogous to the bacterial Min system.
      Plastid nucleoid partitioning may be mediated by binding to envelope or thylakoid
      membranes. Multiple copies of plastid DNA and symmetrical distribution of the
      nucleoids in the plastids may permit faithful transmission to daughter plastids
      via equal binary plastid divisions. Cyanelles retain peptidoglycan wall and
      cyanelle division occurs through septum formation such as bacterial cell
      division. Cyanelle division involves the cyanelle ring analogous to the inner
      stromal plastid-dividing (PD) ring. According to the prevailing hypothesis that
      primary endosymbiosis occurred only once, cyanelle division may represent an
      intermediate stage between cyanobacterial division and the well-known plastid
      division among extant plants. With the secondary plastids, which are surrounded
      by three or four membranes, the PD ring also participates in division of the
      inner two "true" plastid envelope membranes, and the third and the outermost
      membranes divide by unknown mechanisms.

PMID- 12503848
TI  - Cell-cycle responses to DNA damage in G2.
AB  - Cellular reproduction, at its basic level, is simply the passing of genetic
      information from a single parent cell into two daughter cells. As the cellular
      genome encodes all the information that defines a cell, it is crucial that the
      genome be accurately replicated. Furthermore, the duplicated genome must be
      properly segregated so that each daughter cell contains the exact same
      information as the parent cell. The processes by which this occurs is known as
      the cell cycle. The failure of either duplication or segregation of the genome
      can have disastrous consequences for an organism, including cancer and death.
      This article discusses what is known about checkpoints, the surveillance
      mechanisms that monitor both the fidelity and accuracy of DNA replication and
      segregation. Specifically, we will focus on the G2 checkpoint that is responsible
      for ensuring proper segregation of the duplicated genome into the daughter cells
      and how this checkpoint functions to arrest entry into mitosis in response to DNA
      damage.

PMID- 12503849
TI  - Chromosomes of the budding yeast Saccharomyces cerevisiae.
AB  - The mitotic chromosomes of the baker's yeast, Saccharomyces cerevisiae, cannot be
      visualized by standard cytological methods. Only the study of meiotic bivalents
      and the synaptonemal complex and the visualization of chromosome-sized DNA
      molecules on pulsed-field gels have provided some insight into chromosome
      structure and behavior. More recently, advanced techniques such as in situ
      hybridization, the illumination of chromosomal loci by GFP-tagged DNA-binding
      proteins, and immunostaining of chromosomal proteins have promoted our knowledge
      about yeast chromosomes. These novel cytological approaches in combination with
      the yeast's advanced biochemistry and genetics have produced a great wealth of
      information on the interplay between molecular and cytological processes and have
      strengthened the role of yeast as a leading cell biological model organism.
      Recent cytological studies have revealed much about the chromosomal organization
      in interphase nuclei and have contributed significantly to our current
      understanding of chromosome condensation, sister chromatid cohesion, and
      centromere orientation in mitosis. Moreover, important details about the
      biochemistry and ultrastructure of meiotic pairing and recombination have been
      revealed by combined cytological and molecular approaches. This article covers
      several aspects of yeast chromosome structure, including their organization
      within interphase nuclei and their behavior during mitosis and meiosis.

PMID- 12503850
TI  - Proteinases and their inhibitors in the immune system.
AB  - The most important roles of proteinases in the immune system are found in
      apoptosis and major histocompatibility complex (MHC) class II-mediated antigen
      presentation. A variety of cysteine proteinases, serine proteinases, and aspartic
      proteinases as well as their inhibitors are involved in the regulation of
      apoptosis in neutrophils, monocytes, and dendritic cells, in selection of
      specific B and T lymphocytes, and in killing of target cells by cytotoxic T cells
      and natural killer cells. In antigen presentation, endocytosed antigens are
      digested into antigenic peptides by both aspartic and cysteine proteinases. In
      parallel, MHC class II molecules are processed by aspartic and cysteine
      proteinases to degrade the invariant chain that occupies the peptide-binding
      site. Proteinase activity in these processes is highly regulated, particularly by
      posttranslational activation and the balance between active proteinases and
      specific endogenous inhibitors such as cystatins, thyropins, and serpins. This
      article discusses the regulation of proteolytic processes in apoptosis and
      antigen presentation in immune cells and the consequences of therapeutic
      interference in the balance of proteinases and their inhibitors.

PMID- 12503851
TI  - Comparative analysis of spore coat formation, structure, and function in
      Dictyostelium.
AB  - Dictyostelium produces spores at the end of its developmental cycle to propagate
      the lineage. The spore coat is an essential feature of spore biology contributing
      a semipermeable chemical and physical barrier to protect the enclosed amoeba. The
      coat is assembled from secreted proteins and a polysaccharide, and from cellulose
      produced at the cell surface. They are organized into a polarized molecular
      sandwich with proteins forming layers surrounding the microfibrillar cellulose
      core. Genetic and biochemical studies are beginning to provide insight into how
      the deliveries of protein and cellulose to the cell surface are coordinated and
      how cysteine-rich domains of the proteins interact to form the layers. A
      multidomain inner layer protein, SP85/PsB, seems to have a central role in
      regulating coat assembly and contributing to a core structural module that
      bridges proteins to cellulose. Coat formation and structure have many parallels
      in walls from plant, algal, yeast, protist, and animal cells.

PMID- 12503852
TI  - Pancreatic Duodenal Homeobox (PDX-1) in health and disease.
AB  - Insulin is expressed exclusively in the adult beta-cells of the islets of
      Langerhans. Pancreatic Duodenum Homeobox-1 (PDX-1) is a major regulator of
      transcription in these cells. It transactivates the insulin gene by binding to a
      specific DNA motif in its promoter region. Glucose, the main physiological
      regulator of insulin secretion, also regulates insulin gene transcription through
      PDX-1. While acute exposure to high glucose concentrations causes an increase in
      PDX-1 binding, and consequently in insulin mRNA levels, chronic hyperglycemia
      (toxic to the beta-cell) leads to a decrease in PDX-1 and insulin levels. PDX-1
      is absolutely required for pancreas development. In view of the selective
      expression in adult beta-cells, pancreatic agenesis in both the pdx-1 null mouse
      and a human carrying a homozygous mutation of PDX-1 was an unexpected and
      remarkable finding. The homozygous clinical phenotype was neonatal diabetes
      mellitus (DM) and exocrine insufficiency. Heterozygosity for PDX-1 mutations was
      found in some individuals with a newly characterized subtype of maturity-onset
      diabetes of the young (MODY4) and in others with type 2 DM. This review
      underlines the unique role of PDX-1 in maintaining adult beta-cell-specific
      functions in normal and disease-related states.

PMID- 12503853
TI  - Genital surgery among females with congenital adrenal hyperplasia: changes over
      the past five decades.
AB  - The treatment of intersex patients, including any patient born with genital
      ambiguity, is being reassessed. The re-evaluation is primarily focused upon the
      indications for and age of genital surgery, the impact of prenatal androgen
      levels upon gender development, and the potential for maximum sexual
      responsiveness as an adult. As a background to document changes in genital
      surgery for females with 21-hydroxylase congenital adrenal hyperplasia, this
      report is a review of surgical treatment of this most common form of genital
      ambiguity. Results document changes in the 1960s from clitorectomy to
      clitoroplasty using more refined techniques, but more interestingly a choice by
      parents against any surgery during childhood. This shift preceded the current
      impetus from intersex support groups. It appears to result from an appreciation
      by parents of variation in female genital configurations plus a realization that
      the clitoris will regress with the withdrawal of excessive androgens with
      relative size diminishing as growth proceeds. The primary impetus for this shift
      apparently has not been to preserve the vascular and neural supply to enhance
      sexual responsiveness, since parents in the past assumed that such could be
      preserved with appropriate surgical techniques.

PMID- 12503854
TI  - Birth size and neonatal levels of major components of the IGF system:
      implications for later risk of cancer.
AB  - Pre- and perinatal conditions and processes may affect the risk for some forms of
      cancer in later life, while the insulin-like growth factor (IGF) system may play
      a role in both early somatic growth and later carcinogenesis. Birth weight and
      length, and the variation of major components of the IGF system immediately after
      birth, were analyzed in relation to selected physiological and pathological
      variables. The study comprised 331 healthy full-term newborns from whom blood
      samples were taken during routine phlebotomy no later than the fifth day of life.
      Measurements of IGF-I, IGF-II and IGF-binding protein-3 concentrations were
      performed. Birth length and weight were measured and information on socio
      economic and medical variables was recorded. The concentrations of all three
      proteins were lower when blood bilirubin levels were high, possibly as a result
      of compromised liver function and/or as a component of an activated acute phase
      reaction. Birth weight was significantly higher by about 46 g among children
      whose IGF-I was higher by one SD, while the associations of birth weight and
      length with other components of the IGF system were in the predicted directions,
      albeit only in trend. We conclude that in early life, growth is related to the
      IGF system, mostly IGF-I. The latter is lower in children with jaundice, possibly
      because of hepatic dysfunction and/or as part of an acute phase reaction. We
      speculate that elevations of IGF-I in early life might explain the increased risk
      of cancer in individuals born with a higher birth weight.

PMID- 12503855
TI  - Precocious puberty: an endocrine manifestation in congenital toxoplasmosis.
AB  - We reviewed retrospectively seven children with congenital toxoplasmosis and
      precocious puberty. All seven showed very high levels of LH (25.2-155.0 IU/ml)
      and FSH (7.1-38.2) upon stimulation with GnRH. Three of them showed low GH
      response to an insulin tolerance test. All the children had severe mental
      retardation. We emphasize that children with congenital toxoplasmosis should have
      their hypothalamopituitary function evaluated even in subclinical situations that
      could be responsible for endocrinological disturbances such as precocious
      puberty.

PMID- 12503856
TI  - Immunological findings in patients with autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy (APECED) and their family members: are heterozygotes
      subclinically affected?
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; APS-1) is
      an autosomal recessive autoimmune disease, caused by mutations in the AIRE
      (autoimmune regulator) gene. Due to the proposed role of AIRE in central immune
      tolerance, the immune investigation of four females diagnosed with APECED, their
      siblings, parents and 14 age-matched controls was performed. The parameters
      analyzed included immunoglobulins, autoantibodies, cellular immunity and
      production of cytokines IFNgamma, IL-4 and IL-10, reflecting Th1xTh2 balance. Low
      IFNgamma levels (455 +/- 191 pg/ml) were detected in all affected girls compared
      to controls (910 +/- 406 pg/ml). Two girls with homozygous R257X mutations showed
      similarly marked elevation of IgM and increase of CD3+CD4+ lymphocytes. Positive
      autoantibodies against smooth muscle were found in one affected girl; another
      girl and her mother had antibodies against gastric parietal cells. Interestingly,
      all fathers had dramatically elevated levels of IgA and activated T lymphocytes.
      High frequency of abnormal immune results among parents is a novel finding which
      might suggest a subclinical immune deficit in heterozygotes with AIRE mutations.

PMID- 12503857
TI  - Incidence and prevalence of childhood type 1 diabetes mellitus in Germany--model
      based national estimates.
AB  - Fitting a Poisson model to national data on the incidence of type 1 diabetes
      mellitus (T1DM) under 5 years (1993-95) and to age-specific incidence data from
      three different German regions (age groups 0-4, 5-9, 10-14, 15-19 years, 1988
      1995), national age-specific incidences of T1DM in childhood were estimated. From
      these the age-standardized national incidence and prevalence were derived for age
      groups 0-15 and 0-19 years. In 1993-95 the age-standardized national incidences
      (95% CIs) in the age groups 0-14 and 0-19 years were 14.2 (12.9-15.5) and 17.0
      (15.2-18.8) per 100,000 person-years, respectively. The respective national
      prevalences were 86.7 (83.4-90.0) and 140.2 (134.3-146.1) per 100,000 persons.
      These estimates of the national incidence and prevalence of T1DM for the mid
      1990s were about twofold higher than estimates from the former Eastern Germany in
      the late 1980s. This striking high frequency of T1DM in Germany has an important
      impact on clinical and economic aspects of diabetes care in childhood and
      adolescence.

PMID- 12503858
TI  - Mutational analysis and genotype-phenotype correlation in patients with classic
      21-hydroxylase deficiency from transylvania (north-west Romania).
AB  - The regional incidence of 21-hydroxylase deficiency, its mutational spectrum and
      the correlation of genotype and phenotype has been studied by European, American
      and Latin-American groups. However, little information is known about the
      molecular background of the disease in patients from Central-Eastern Europe. The
      present study aimed to genotype a group of patients from Transylvania, the north
      western part of Romania, in order to gain some insight into the molecular pattern
      and the genotype-phenotype correlation of congenital adrenal hyperplasia (CAH) in
      this region. We genotyped 17 patients with classic 21-hydroxylase deficiency and,
      whenever available, their parents in order to verify mutational segregation. The
      patients came from 13 unrelated families. DNA was prepared from peripheral blood
      leucocytes and four gene fragments were amplified by PCR. The 21-hydroxylase gene
      (CYP21B) was completely sequenced and analyzed for point mutations or deletions.
      Percentage distribution of mutations was as follows: 12G--34.6%, deletions and
      large conversions (del)--19.2%, P30L--15.4%, 1172N--15.4%, P30L+I2G+del8bp
      (triple mutation)--11.5%, and R356W--3.8%. Mutational percentage distribution
      compared to other Latin populations is higher for I2G and I172N and lower for
      deletions, while the P30L mutation was found at a higher rate than in any other
      analyzed population. Some differences may arise from the low patient number and
      from ethnic particularities. The incidence of compound heterozygotes in our group
      was 76.5%. The genotype seemed to correlate fairly well to phenotype, with a
      general concordance rate of 82.35%. Clear divergence was found in two patients
      with the simple virilizing form, exhibiting a homozygous status for I2G and del,
      respectively. This study offers the first information about the molecular
      pathology of CAH in Romania and should help to improve management and clinical
      outcome for patients with CAH in Transylvania. Hopefully, it might also be the
      first step towards exact and accurate prenatal diagnosis in our country.

PMID- 12503859
TI  - Adrenal steroids synthesis during acute infectious diseases in infants.
AB  - An increase in plasma 17OHP found in infants requiring differential diagnosis
      between septic shock and adrenal failure led us to look for adrenal steroids
      pattern during infection. INFANTS AND METHODS: 56 infants, 1-6 months old, were
      studied during infection of different degrees of severity. Plasma cortisol,
      17OHP, androstenedione, DHEA, DHEA-S and testosterone were measured. RESULTS: 24
      patients showed an expected cortisol elevation. One child had a low cortisol
      level. The concentration of 17OHP was above 6.0 nmol/l (200 ng/dl) in 41 patients
      and above 30.2 nmol/l (1,000 ng/dl) in 10. Higher 17OHP levels and more severe
      diseases correlated positively. CONCLUSIONS: During infectious diseases some
      patients demonstrated not only cortisol elevation but also 17OHP as high as that
      observed in NC-CAH. We suggest that if 17OHP elevation is not characteristic of
      SL-CAH, glucocorticoid therapy should be started and an ACTH test should be
      performed after recovery before ruling out this pathology.

PMID- 12503860
TI  - Cerebral midline developmental anomalies: endocrine, neuroradiographic and
      ophthalmological features.
AB  - BACKGROUND: Hypopituitarism may occur in patients with midline cerebral defects
      (MCD), including septo-optic dysplasia (SOD). HESX1 gene mutations have been
      associated with SOD. OBJECTIVE: To evaluate the endocrine, ophthalmological and
      neuroradiographic abnormalities in 18 patients with MCD and SOD without mutations
      at the HESX1 locus. STUDY DESIGN: The diagnosis of hypothalamic and pituitary
      abnormalities was confirmed by clinical findings and basal hormone values or
      functional tests. All patients underwent ophthalmological examination and
      neuroradiologic studies by MRI. RESULTS: The diagnosis of hypothalamic and
      pituitary abnormalities varied from 3 days to 13 years. Endocrine abnormalities
      were found in 88% of the patients: GH deficiency (72%), hypothyroidism (66%),
      hypogonadism (45%), diabetes insipidus (27%), adrenal insufficiency (10%), and
      precocious puberty (5%). Psychomotor retardation was observed in 55% and seizures
      in 22%. Visual status varied from normal to blindness. MRI confirmed
      heterogeneous intracranial malformations. CONCLUSIONS: Our data support the need
      for systematic and periodic endocrine evaluation of patients with MCD using a
      multidisciplinary approach.

PMID- 12503861
TI  - Bone mineral density in children and young adults with beta-thalassemia trait.
AB  - BACKGROUND: Homozygous beta-thalassemia is a hereditary hematological disease due
      to defective beta-globin synthesis. Consequently, there is ineffective
      erythropoiesis and increased peripheral hemolysis. Increased erythropoiesis in
      bone marrow results in expansion of marrow cavity and reduced bone mass. Patients
      with heterozygous beta-thalassemia or beta-thalassemia trait may have mild
      anemia, and consequently mildly increased erythropoiesis. Whether modestly
      increased erythropoiesis might decrease bone mass is not well established.
      OBJECTIVE: To evaluate bone mineral density (BMD) in children and young adults
      with beta-thalassemia trait. METHODS: Thirty-one healthy young adults aged 20-45
      yr and 26 healthy children aged 8-15 yr with beta-thalassemia trait were enrolled
      in the study. BMD was determined by dual X-ray absorptiometry (DEXA).
      Determinations of intact parathormone (PTH), 25-hydroxyvitamin D (25-OHD), and
      bone markers were performed. RESULTS: In adults, all had z-scores of BMD more
      than -2 above the mean. The mean z-scores of BMD of lumbar spine, radius and
      femoral neck were 0.11, -0.10 and 0.41, respectively. In children, only two of 26
      had z-scores of lumbar spine BMD more than -2 below the mean. The mean z-scores
      of BMD of total body, lumbar spine, radius and femoral neck were 0.12, -0.28,
      0.30 and -0.14, respectively. All subjects had normal PTH, 25-OHD and bone
      markers levels. CONCLUSION: beta-Thalassemia trait is not a contributing factor
      for osteopenia/osteoporosis in children and young adults.

PMID- 12503862
TI  - Low vertebral cancellous bone density in peripubertal girls with Turner's
      syndrome and boys with hypogonadism.
AB  - OBJECTIVE: To characterize the changes of vertebral cancellous bone density in
      children with hypogonadism. STUDY DESIGN: Quantitative computed tomography (QCT)
      values of vertebral cancellous bone in 21 girls with Turner's syndrome, 12 boys
      with hypogonadism, and 46 age-matched controls (24 boys, 22 girls) were studied.
      The subjects were divided into the following subgroups by the age (year) at the
      time of the measurement: A. 4-6.9; B. 7-9.9; C. 10-12.9. RESULTS: QCT values for
      Turner's syndrome vs control girls in the same age groups (A, B, and C) were
      (mean +/- SD) 226 +/- 36 vs 216 +/- 31 (NS), 193 +/- 29 vs 220 +/- 33 (NS), and
      177 +/- 32 vs 217 +/- 17 (p < 0.01) mg/cm3, respectively. Those for boys with
      hypogonadism vs control boys (A, B, and C) were 236 +/- 15 vs 240 +/- 12 (NS),
      187 +/- 21 vs 225 +/- 28 (p < 0.05), and 172 +/- 11 vs 216 +/- 26 (p < 0.0001)
      mg/cm, respectively. The cross-sectional data for Turner's syndrome and boys with
      hypogonadism had significant negative correlation with chronological age (r =
      0.59; p < 0.001). CONCLUSION: These results showed that vertebral cancellous bone
      density in children with hypogonadism began to decrease during the peripubertal
      period in contrast to the constant values in controls, suggesting that a small
      amount of gonadal steroid in healthy children has an important role in
      maintaining normal bone density.

PMID- 12503863
TI  - Thyroid dysfunction and high thyroid stimulating hormone levels in children with
      Down's syndrome.
AB  - In order to delineate the spectrum of thyroid abnormalities in children with
      Down's syndrome (DS), first visit height data (SDS) and serum TSH, T4 and
      antiperoxidase antibodies concentrations were retrospectively evaluated in 137
      children (71 girls) with DS (0.04-16 years). RESULTS: Congenital hypothyroidism
      was detected in 2.9% of patients. Thyroid disease occurred in 9%: four
      hyperthyroidism and eight hypothyroidism. Overt thyroid disease was always
      related to thyroid autoimmunity. The remaining 121 patients had normal T4 levels
      but increased mean TSH compared with controls (4.7 +/- 2.8 vs 2.3 +/- 1.3 mU/l).
      According to TSH levels, they were divided into two groups: G1 (n = 68) with
      normal TSH (<5 mU/l), and G2 (n = 53) with high TSH (> 5 mU/l). T4 levels were
      significantly lower in G2 (p < 0.01 vs G1 and controls). Height SDS was not
      different. CONCLUSIONS: Thyroid disorders are frequent in children with DS.
      Subtle thyroid abnormalities found in patients with DS with no evidence of
      clinical dysfunction need further investigation to demonstrate whether there is a
      need for therapeutic intervention.

PMID- 12503864
TI  - Pituitary non-secreting macroadenoma apoplexy in an adolescent. patient report
      and review of the literature.
AB  - Pituitary macroadenomas are rare in children and adolescents, and when
      encountered are usually hormone secreting. Symptomatic pituitary non-secreting
      macroadenoma apoplexy in an adolescent is rare and potentially life-threatening.
      A 15 year-old patient is described, hospitalized due to headache, fever and
      photophobia 4 days prior to admission. A meningeal syndrome was postulated, based
      on clinical examination and cerebrospinal fluid testing. However, clinical
      examination and hormone testing revealed partial failure of the anterior
      pituitary. Computed tomography of the brain demonstrated a space-occupying lesion
      of the pituitary. Magnetic nuclear resonance imaging suggested the presence of a
      pituitary macroadenoma. Hypophysectomy was performed. Histological examination
      revealed an extensive infarction of a pituitary adenoma. Hormonal substitution
      with thyroxine and corticosteroids was administered. This report emphasizes that
      pituitary non-secreting macroadenoma apoplexy may rarely be the cause of headache
      and fever in an adolescent, thus causing difficulties in differential diagnosis
      from acute meningitis.

PMID- 12503865
TI  - Persistence of Mullerian remnants in complete androgen insensitivity syndrome.
AB  - One of the unusual findings in androgen insensitivity syndrome (AIS) is the
      persistence of Mullerian derivatives. Several hypotheses have been advanced to
      explain such persistence: the coincidental occurrence of mutations affecting the
      androgen receptor (AR) and the synthesis and/or action of anti-Mullerian hormone
      (AMH); the loss of AMH paracrine action due to early testicular descent; the
      exposure to drugs such as diethylstilbestrol. We describe a patient with complete
      AIS for whom surgical and laboratory findings rule out all these hypotheses. She
      has a missense mutation on the AR gene but no mutations were detected on the
      genes coding for AMH and AMH receptor. The gonads were found very close to the
      Mullerian structures (enough to exert a paracrine action), gonadal tissue stained
      positively for AMH, and yet Mullerian derivatives were present and well
      developed. These findings indicate the possibility of interactions between the
      androgen receptor and AMH action.

PMID- 12503866
TI  - Pseudohypoaldosteronism type 1 and respiratory distress syndrome.
AB  - We present a patient born at 31 weeks gestation with respiratory distress
      syndrome (RDS) which did not respond to surfactant. He also developed
      hyponatremia, hyperkalemia and dehydration with increased sweat electrolytes
      despite high levels of serum aldosterone, thus systemic pseudohypoaldosteronism
      type 1 (PHA-1) diagnosis was made. Systemic PHA-1 is caused by mutations of
      amiloride-sensitive epithelial sodium channel (ENaC) genes. Because ENaC is a
      rate-limiting step for sodium absorption by epithelial cells, not only of the
      renal tubule but also of the lung epithelium, patients with PHA-1 with pulmonary
      symptoms have sometimes been reported. However, our patient appears to be the
      second reported human case of both neonatal RDS and PHA-1, and the first
      description, with increased sweat electrolytes, of a premature baby with systemic
      PHA-1 and RDS.

PMID- 12503867
TI  - Pheochromocytoma presenting as stroke in two Taiwanese children.
AB  - Pheochromocytoma is a rare tumor and accounts for about 1% of pediatric
      hypertension. Its diagnosis is important because the hypertension is usually
      curable by eradication of the tumor. We report two Taiwanese children with
      pheochromocytoma presenting as stroke. Patient 1 developed a cerebral infarction
      and patient 2 had an intracranial hemorrhage. Abdominal MRI of patient 1 showed
      an extraadrenal tumor 5.1 x 4 x 4.7 cm in size and abdominal CT of patient 2
      revealed a left adrenal mass 4 x 2.9 x 4 cm in size. 24-h urinary excretion of
      norepinephrine for patients 1 and 2 were 1480.8 and 3279 microg/day,
      respectively. Preoperative alpha- and beta-adrenergic blockade was used for
      hypertension control. Both patients underwent successful tumor resection, upon
      which blood pressure and 24-h urinary excretion of catecholamines returned to
      normal without any further medication. They have been free from hypertension for
      4 years (patient 1) and 2 years (patient 2).

PMID- 12503868
TI  - Re: "An activating mutation of the thyrotropin receptor gene in hereditary non
      autoimmune hyperthyroidism" by Yung-Seng Lee et al. J Pediatr Endocrinol Metab
      2002; 15: 211-215.

PMID- 12503869
TI  - First evidence on occurrence of gymnodimine in clams from Tunisia.
AB  - Among several batches of clams harvested in Tunisia and imported to France, a
      small number of them were found to be neurotoxic to mice (intraperitoneal
      injection) as determined by the diarrhetic shellfish poisoning (DSP) bioassay
      developed by Yasumoto et al. (1978). The present study was conducted to confirm
      the nature of the toxic agent, suspected to be gymnodimine. Liquid chromatography
      tandem mass spectrometry analyses unequivocally revealed the presence of
      gymnodimine in the shellfish, making Tunisia the second country, after New
      Zealand, where shellfish contamination with this phycotoxin is reported.
      Gymnodimine B and C analogues were not detected in the clam samples. Gymnodimine
      preferentially accumulates in the digestive gland of the Tunisian clams, although
      substantial amounts are also found in the meat.

PMID- 12503870
TI  - Occurrence of a food poisoning incident by palytoxin from a serranid Epinephelus
      sp. in Japan.
AB  - Between October 30 and November 4, 2000, eleven persons were intoxicated due to
      ingestion of a serranid fish Epinephelus sp. in Kochi Prefecture, Japan. Their
      symptoms were mainly featured by severe muscle pain, low back pain, and discharge
      of black urine. Serum creatine phosphokinase (CPK) levels of victims were higher
      (700-23,800 IU/l) than normal values, and their recovery times were more than one
      month. Immediately after the incident, the leftovers were collected for
      investigation. The causative agent was identified as palytoxin (PTX) on the basis
      of delayed haemolytic activity which was inhibited by an anti-PTX antibody and
      ouabain (g-strophanthin). To our knowledge, this is the first report on palytoxin
      poisoning with serranid fish.

PMID- 12503871
TI  - Biological activities of the crude skin toxin of the Suez Gulf oriental catfish
      (Plotosus lineatus) and its antitumor effect in vivo (mice).
AB  - Quantitative determination of newly reported enzymes activity in the crude skin
      toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase,
      lesser activities of phospholipase A2, lactate dehydrogenase (LDH),
      cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase
      (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has
      a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen
      dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich
      carcinoma-bearing mice demonstrated by an increase in the mean survival time
      (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the
      relative weights of heart and liver after three weeks, while modulating the
      elevation in the relative spleen weight throughout the treatment periods (three,
      six, and nine weeks). The levels of serum triglyceride, total cholesterol, and
      liver total lipids were normalized after three weeks, whereas the serum albumin
      and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase
      activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and
      creatine kinase (CK) activities were significantly modulated throughout the
      treatment periods. Histological examinations of the tumor and liver tissues of
      treated tumor-bearing animals were carried out. Tumor tissues showed many
      cytolytic and cytopathic changes after treatment, while liver tissues showed
      moderate dysplastic changes after six weeks of treatment, which became more
      marked after nine weeks.

PMID- 12503872
TI  - Fishing for bioactive substances from scorpionfish and some sea urchins.
AB  - Venom proteins from the dorsal spine of two scorpionfish, Hypodytes rubripinnis
      and Synanceia verrucosa were assayed for mitogenicity and cytotoxicity. The two
      venoms had both mitogenic and cytotoxic activity on murine splenocytes and murine
      P388 leukemic cells. In H. rubripinnis, the second gel chromatographic fraction
      showed cytotoxic activity on P388 leukemic cells. On native PAGE, the
      glycoprotein isolated by concavalin A sepharose chromatography appeared to have a
      molecular mass of 110 kDa. In addition, two D-galactose-binding lectins (SUL-I
      and SUL-II) and a heparin-binding lectin (TGL-I) were purified from the
      globiferous pedicellariae of the toxopneustid sea urchins, Toxopneustes pileolus
      and Tripneustes gratilla, respectively. SUL-I (Nakagawa et al., 1999a) had
      mitogenic activity and cytotoxic activity but SUL-II and TGL-I did not. SUL-I did
      not show sequence homology to SUL-II. A hemolytic lectin with a molecular mass of
      29 kDa was isolated from the coelomic fluid of T. gratilla. The hemolytic
      activity of the lectin was dependent on Ca2+ concentration and inhibited by
      lactose. The present results suggest that some species of scorpionfish and sea
      urchins may be novel sources for biologically active substances such as anti
      tumor compounds or new lectins.

PMID- 12503873
TI  - Evidence for a neurotoxic activity in crude venom of the stonefish (Synanceia
      verrucosa).
AB  - The neurotoxic effects of the Synanceia verrucosa venom were investigated in
      rodents. After intracranial injection in mice (50-125 ng/g), venom induced
      constant symptoms such as ataxia, circling, partial or complete reversible limbs
      paralysis, scratching, rolling, sleep-like periods and violent clonic seizure
      conducing in few seconds to death. EEG alterations occurring in rat brain after
      intracerebroventricular injection (50-100 microg) were precised. An initial phase
      was characterized by short repetitive tonic seizure periods together with a
      significant rise of the relative power in the delta band, no significant
      modification of the theta II rhythm (4-7 Hz), a decreasing of energy in theta I
      (7-12 Hz) and 15-40 Hz bands. A second phase was characterized by a marked
      generalized slowing with transient drastic decreasing of the amplitude and
      flattening of cortical EEG (comatose state) as the main elements. Propanolol did
      not reverse the EEG effects of the venom except a slight decrease of the slow
      wave amplitude. Previous intracerebroventricular administration of a K+(ATP)
      blocker generally decrease the delay of death. Histopathologic examination of the
      brain of surviving animals did not reveal any microscopic lesions. These results
      suggest (1) a complex mechanism of the venom in its neuropathologic expression;
      (2) at the doses tested, symptoms are not related to adrenergic pathways, K+(ATP)
      channel opener (verrucotoxin) is not implied in the neurotoxic effect, and the
      effect of the venom, which not affecting the theta II rhythm, seemed not to be
      exerted through cholinergic pathway.

PMID- 12503874
TI  - Effects of toxic dinoflagellates and toxin biotransformation in bivalves.
AB  - Attempts were made to elucidate the different responses of shellfish to paralytic
      shellfish poison (PSP) and the PSP donor Alexandrium minutum T1. Five species of
      edible bivalves (Crassostrea gigas, Meretrix lusoria, Mytilus edulis, Ruditapes
      philippinarum, and Soletellina diphos) were collected and examined for
      susceptibility to PSP and PSP donor. It was determined that all five bivalves had
      low susceptibility to PSP following an intramuscular injection (> 300 MU/20 g).
      The abnormal effects on bivalves were species-specific and varied with the
      concentration of A. minutum T1. Judging from the LC50 data (medium lethal
      concentration), the resistance of bivalves to the toxic dinoflagellate was as
      follows (least to most resistant): C. gigas < R. philippinarum < M. lusoria < M.
      edulis, S. diphos. With the exception of S. diphos, the bivalves accumulated very
      little toxin (< 2 MU/g edible tissue) when they were exposed to 10(7) cells/L of
      A. minutum for four days. The toxin levels in S. diphos increased with exposure
      time to the toxic dinoflagellates and accumulated primarily in the digestive
      gland (88-100%), followed by the gill (0-10%), and other organs (0-8%). Although
      the concentrations of toxin components in the digestive gland were found to be
      variable during the exposure period, the toxin profile in the digestive gland of
      S. diphos during the early exposure period was similar to that of A. minutum.
      Moreover, toxin components in the gills and in other organs were retained at near
      constant concentrations during the exposure period.

PMID- 12503875
TI  - Improved purification and yield of the Egyptian snake Cerastes cerastes antitoxin
      by the use of caprylic acid.
AB  - The aim of this study was to obtain anti-snake antiserum by optimizing the
      conditions of extraction and purification and test its ability to neutralize
      local myonecrosis. Extraction and purification was achieved through adjustment of
      the pH, pepsin concentration, time of digestion, and caprylic acid concentration.
      Our results indicate that the best conditions to obtain anti-snake antiserum from
      ammonium sulfate fractionated plasma are pH 3.3, 3.5 g/l pepsin, digestion for 90
      min at 37 degrees C, and 0.5% caprylic acid. Antiserum purified using this method
      has greater neutralizing ability of myonecrosis than ammonium sulfate (ammSO4)
      fractionated product.

PMID- 12503876
TI  - Cross neutralization of dangerous snake venoms from Africa and the Middle East
      using the VACSERA polyvalent antivenom. Egyptian Organization for Biological
      Products & Vaccines.
AB  - This study was performed to assess the ability of polyvalent snake venom anti
      serum, produced by the Egyptian Organization for Biological Products & Vaccines
      (VACSERA), to neutralize several toxic activities of snake venoms, not only of
      those included in the antivenom mixture, but also some additional venoms of
      snakes from Egyptian, African, and Middle Eastern habitats. In general, the
      results revealed that polyvalent snake venom anti-serum from VACSERA is highly
      effective in neutralizing Egyptian snake venoms, especially Naja haje, Naja
      nigricolles, Naja pallida, Cerastes cerastes, Cerastes cerastes cerastes,
      Cerastes vipera, Pseudocerastes persicus fieldi, and Walterinnisia egyptia. The
      antivenom was also effective against Naja haje, Walterinnisia egyptia, and Bites
      aritans from Saudi Arabia. High activity was obtained against venoms from Naja
      haje, Naja nigricolles, and Naja pallida of Sudan, as well as the African Naja
      melanoleuca, Naja mossambica, Naja naja oxiana, Bites gabonica, and Vipera
      lebetina. Only moderate effectiveness was obtained with Echis coloratus and Echis
      carinatus, and the polyvalent antiserum was ineffective against the venom of Naja
      nivea.

PMID- 12503877
TI  - Purification and characterization of alpha-mucrofibrase, a novel serine protease
      with alpha-fibrinogenase activity from the venom of Chinese Habu (Trimeresurus
      mucrosquamatus).
AB  - A novel fibrinogenolytic protease, named alpha-mucrofibrase, was purified from
      the venom of Chinese Habu (Trimeresurus mucrosquamatus) by DEAE-Sephadex A-50 ion
      exchange chromatography and Sephadex G-100 (super fine) gel filtration alpha
      Mucrofibrase is a single-chain polypeptide of approximately 29 kDa. It is stable
      even at 95 degrees C, and the most susceptible hydrolysis substrate is S-2302. It
      cleaved primarily the Aalpha chain of fibrinogen followed by the Bbeta chain,
      while the gamma chain was partially affected. N-terminal sequence of this
      fibrinogenolytic enzyme has great homology with those of other snake venom serine
      proteases. The esterase activity of alpha-mucrofibrase is inhibited by
      phenylmethylsulfonyl fluoride (PMSF) but not by metal chelator (EDTA), suggesting
      this fibrinogenase belongs to the venom serine protease family.

PMID- 12503878
TI  - L-amino acid oxidase from Trimeresurus jerdonii snake venom: purification,
      characterization, platelet aggregation-inducing and antibacterial effects.
AB  - An L-amino acid oxidase (LAO), designated as TJ-LAO, was purified to homogeneity
      from the venom of Trimeresurus jerdonii by Sephadex G-100 and Q Sepharose HP
      chromatography. The molecular weight of this enzyme was 110 kD as estimated by
      analytical gel filtration and was 55 kD by SDS-polyacrylamide gel
      electrophoresis, suggesting that the enzyme is composed of two subunits. The
      enzyme has an absorption spectrum characteristic of flavoproteins, containing 2
      moles of FMN per mole of enzyme. The N-terminal sequence of TJ-LAO shares high
      homology with other viperid snake venom LAOs. Homology with elapid venom LAO is
      lower. TJ-LAO inhibited the growth of Escherichia coli, Staphylococcus aureus,
      Pseudomonas aeruginosa, and Bacillus megaterium. The antibacterial effect
      associated with LAO activity was elminated with the addition of catalase.
      Platelets in platelet-rich plasma aggregated upon the addition of TJ-LAO. The
      enzyme-induced aggregation was inhibited by catalase, suggesting formation of
      H2O2 was essential for TJ-LAO to induce platelet aggregation. These results
      showed H2O2 formation is important for the biological effects of LAO.

PMID- 12503879
TI  - A pilot experiment for production of Malayan krait antivenom: immunization of
      rabbits with Bungarus candidus venom.
AB  - Immunization with Bungarus candidus venom was performed in four rabbits at high
      dose (initial dose, 75 microg/kg) and low dose (initial dose, 50 microg/kg). Each
      dose group consisted of two rabbits; one rabbit received the venom subcutaneously
      (s.c.) and the other intradermally (i.d.). The venom was injected as emulsified
      solutions with the same volume of Freund's complete adjuvant until the 4th
      immunization, thereafter as plain solutions. By stepwise increments of the
      immunizing dose, the higher dose group received a dose of 200 microg/kg and the
      lower dose group 150 microg/kg after the 5th immunization, respectively.
      Thereafter, seven additional immunizations were performed within six months. All
      rabbits were sacrificed two weeks after the last immunization (12th). Antilethal
      activity of the immunized antisera thus obtained was determined not only with the
      homologous venom but also with two heterologous venoms from Bungarus fasciatus
      and Bungarus flaviceps. Immunodiffusion analysis was also performed with these
      venoms. The results obtained in this pilot trial provided useful information for
      production of Malayan krait antivenom at Queen Saovabha Memorial Institute.

PMID- 12503880
TI  - Biochemical characterization of the soluble alkaline phosphatase isolated from
      the venomous snake W. aegyptia.
AB  - A soluble form of alkaline phosphatase (ALP) has been identified and purified
      from Walterinnesia aegyptia venom using an HPLC system Gold 126/1667 equipped
      with Protein PAK 125 and Protein PAK 60 columns. The enzyme was purified 3.4 fold
      over crude venom with a yield of 37.3%. On SDS-PAGE under non-reduced conditions
      the purified enzyme showed three bands of 212 kD, 80 kD, and 55 kD. However,
      under reducing conditions, the enzyme showed two bands of 80 kD and 55 kD. The
      specific activity of ALP was 24 U/mg with p-nitrophenylephosphate as the
      substrate. During isoelectric focusing experiments the ALP exhibited two bands
      focused at pH 6.2 and 6.8, which suggests that either the enzyme exists as two
      different isoforms or the two bands in IEF may be two subunits of 80 kD and 55
      kD. The kinetic parameters (Km and Vmax) and IC50 of ALP inhibition by L
      phenylalanine, L-leucine, imidazole, caffeine, orthophosphate and permanganate
      were also investigated in the present study. Zinc and cyanide ions at a
      concentration of 15 mM and 10 mM, respectively, completely inhibited the activity
      of W. aegyptia ALP.

PMID- 12503881
TI  - Heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non
      mutagenic in vitro.
AB  - Heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated
      from a marine tunicate collected in Zamboanga, Philippines, as part of a program
      to screen natural products for antiparasitic activity. An in vitro antimalarial
      activity similar to that of quinine was found against the chloroquine-sensitive
      strain Plasmodium falciparum 3D7. The in vitro antimalarial activity was about 20
      times the in vitro cytotoxic activity against L5178Y mouse lymphocytes. A single
      subcutaneous administration of 5 and 20 mg/kg significantly extended survival of
      P. berghei ANKA strain-infected mice but also caused sclerotic lesions at the
      site of injection. A single administration by gavage of 50 mg/kg did not increase
      survival time. The compound was not found to be mutagenic using in vitro
      micromethods for the Ames Salmonella typhimurium assay and the micronucleus assay
      using L5178Y mouse lymphoma cells.

PMID- 12503882
TI  - The occurrence of mycotoxins in key commodities in Bangladesh: surveillance
      results from 1993 to 1995.
AB  - A three-year surveillance program assessed the extent of mycotoxin contamination
      of key foods and feeds grown in Bangladesh. The study also included groundnuts
      utilized as snack food. In the first two phases of the program the samples
      collected were analyzed only for aflatoxins, but in the third phase, as well as
      for aflatoxins, samples were tested for the presence of fumonisin B1, ochratoxin
      A, zearalenone, deoxynivalenol, and T-2 toxin. Of the foods and feeds tested, the
      incidence of aflatoxin contamination varied from low (rice collected from
      farmers' stores, 8%) to high (maize, 67%). However, both the average total
      aflatoxin contents (< 1.0 microg/kg) and the maximum aflatoxin B1 contents (< or
      = 5.0 microg/kg) recorded for pulses, rice and its various products, and wheat
      were low. On the other hand, the levels of contamination of maize, roasted and
      raw groundnuts, and poultry feed were considerably higher, with average total
      aflatoxin B1 contents of 33, 13, 65, and 7 microg/kg, respectively, and maximum
      aflatoxin B1 contents of 245, 79, 480, and 160 microg/kg, respectively. Fumonisin
      B1, ochratoxin A, zearalenone, deoxynivalenol, and T-2 toxin were found, to any
      significant extent, only in some of the maize samples tested, always accompanied
      by aflatoxins. One sample of maize contained five mycotoxins, namely, the
      aflatoxins, fumonisin B1, deoxynivalenol, zearalenone, and ochratoxin A. In a
      limited trial using hospital staff in Dhaka, the analysis of the aflatoxin
      albumin adduct in serum showed that approximately half of the test group had been
      recently exposed to low levels of aflatoxins.

PMID- 12503883
TI  - Age and sex-related difference in levels of nerve growth factor in organs of
      Balb/c mice.
AB  - The presence of nerve growth factor (NGF) is reported in salivary glands of mice
      and sex organs of various male animals. NGF level is reported to be higher in
      salivary glands of male mice in comparison to female. This investigation reports
      the presence of NGF in major organs of Balb/c mice showing quantitative
      differences in NGF according to sex and age. Organs of Balb/c mice from ages 2
      weeks to 9 months were tested for NGF content by immunological tests enzyme
      linked immunosorbent assay (ELISA). Male and female mice for each age group were
      from the same litter. It was revealed that NGF levels increased with age,
      reaching the peak at 4 weeks for male mice versus 3 months for female for similar
      organs. There were consistently lower levels of NGF in the organs of female mice
      in comparison to their male siblings. Most decreased levels of NGF were observed
      in organs of mice with respect to heart, salivary glands, and sex organs, ovaries
      versus testes. The presence of NGF was further revealed in non-neural organs. NGF
      based maturity was reached at 4 months for male mice versus 6 months for females.

PMID- 12503884
TI  - Extremely low nerve growth facior (NGF) activity of sea snake (Hydrophiidae)
      venoms.
AB  - Sea snake venoms contain less protein than those of land snakes (Toom et al.,
      1969). Sea snake venoms lack arginine ester hydrolyzing activity, whereas those
      of Crotalidae and Viperidae have such activity (Tu et al., 1966). Sea snakes live
      in salty water, and their venoms may be different from those of land snakes.
      Because of the difficulty in obtaining sea snake venoms, information about sea
      snake venoms is quite incomplete. NGF is commonly present in the venoms of land
      snakes such as Elapidae, Viperidae, and Crotalidae (Cohen and Levi-Montalcini,
      1956; Lipps, 2002). It is therefore of interest to investigate the presence or
      absence of NGF in sea snake venoms. In order to investigate the presence or
      absence of NGF, five sea snake venoms were selected. Lapemis hardwickii
      (Hardwick's sea snake) and Acalyptophis peronii venom were obtained from the Gulf
      of Thailand. Hydrophis cyanocinctus (common sea snake) and Enhydrina schistosa
      (beaked sea snake) venom were obtained from the Strait of Malacca. Laticauda
      semifasciata (broad band blue sea snake) venom was also examined and the venom
      was obtained from Gato Island in the Philippines.

PMID- 12503885
TI  - Coarse granulation in the perivitelline space and IVF-ICSI outcome.
AB  - PURPOSE: To study the effect of the presence of coarse granules in the
      perivitelline space (PVS) of oocytes on embryonic development, and on
      implantation and pregnancy rates in IVF. METHODS: The study population included
      24 patients treated during the period 1995-2000. The majority or all of their
      oocytes exhibited repeatedly coarse granulation in the PVS. Clinical and
      laboratory cycle characteristics of their 65 IVF-ICSI cycles and the resulting
      implantation and pregnancy rates were compared to a matched control group of 65
      IVF- ICSI cycles without granulation in the PVS. RESULTS: A total of 623 oocytes
      were retrieved, 418 oocytes fertilized, and 246 embryos were transferred in the
      study group. No difference was detected between the study and control group with
      regard to patients' clinical data, IVF cycle characteristics, mean number of
      oocytes retrieved and fertilized, and mean number of embryos transferred. Only
      seven pregnancies were achieved in the study group, leading to pregnancy and
      implantation rates of 10.7 and 5.7%, respectively. Pregnancy and implantation
      rates were significantly higher in the control group of matched IVF-ICSI cycles
      without granulation in the PVS (32.5 and 11.5%, respectively). CONCLUSIONS: The
      presence of coarse granules in the PVS correlates with low implantation and
      pregnancy rates in IVF-ICSI cycles and might be regarded as a distinct entity,
      part of the yet poorly defined condition of "egg factor infertility."

PMID- 12503886
TI  - Human chorionic gonadotropin combined with progesterone for luteal support
      improves pregnancy rate in patients with low late-midluteal estradiol levels in
      IVF cycles.
AB  - PURPOSE: To investigate how late-midluteal estradiol levels relate to the
      pregnancy outcome in IVF cycles, and to assess whether human chorionic
      gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients
      with low late-midluteal estradiol levels. METHODS: The pregnancy rate of 436
      women undergoing first IVF cycles with long protocol and luteal support with
      progesterone alone were analyzed. Unsuccessful women with low late-midluteal
      estradiol levels (< 100 pg/mL) proceeded with the exploratory second IVF cycles
      where they were randomly given with either progesterone alone (P protocol) or hCG
      +progesterone (P+hCG protocol) for luteal support. RESULTS: Pregnancy rate in
      women with low late-midluteal estradiol levels was significantly lower compared
      to that with medium (100-500 pg/mL) and high (> 500 pg/mL) levels (13.3, 26.8,
      and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol
      levels and produced a significantly higher pregnancy rate (31.7%) than P protocol
      (13.7%). CONCLUSIONS: hCG in combination with progesterone for luteal support was
      suggested to benefit women undergoing IVF with low late-midluteal estradiol
      levels.

PMID- 12503887
TI  - The maturity of human cumulus-free oocytes is positively related to blastocyst
      development and viability.
AB  - PURPOSE: We investigated whether the human oocyte maturity at the removal of
      cumulus/corona cells affects the embryo outcome in vitro. METHODS: A total of 620
      oocytes, which subsequently underwent blastocyst culture, were included in this
      analysis. Oocytes that were in prophase or Metaphase I of meiosis at the removal
      of cumulus/corona cells were in Group II. Oocytes that were in Metaphase II at
      the removal of cumulus/corona cells were in Group I. RESULTS: Group I oocytes
      yielded the highest fertilization rates (96.3% vs. 77.1%, P < 0.001). The
      incidence of Group II oocytes developing to the blastocyst stage was
      significantly less than from Group I oocytes (38.1% vs. 86.1%, P < 0.001). The
      percentage of top-scoring blastocysts from Group I oocytes was higher than that
      of Group II oocytes (95.4% vs. 76.2%, P < 0.001). CONCLUSIONS: Oocyte maturity at
      the removal of cumulus/corona cells needs to be considered in selecting good
      quality blastocysts for embryo transfer.

PMID- 12503888
TI  - The added value of embryo cryopreservation to cumulative ongoing pregnancy rates
      per IVF treatment: is cryopreservation worth the effort?
AB  - PURPOSE: To calculate the added benefit of a cryopreservation program to the
      cumulative ongoing pregnancy rate over a maximum of three cycles of IVF. METHODS:
      A total of 1251 couples beginning their first IVF treatment between January 1995
      and December 1999 were evaluated. Ongoing pregnancies from fresh and subsequent
      cryopreserved embryo transfer cycles were analyzed. Pregnancies arising from the
      cryopreservation cycle were considered to augment the cumulative pregnancy rate
      when no ongoing pregnancy arose from the fresh embryo transfer cycle. RESULTS:
      The ongoing pregnancy rate per cryopreserved embryo transfer was 11.7%. The
      cumulative ongoing pregnancy rate following three successive started fresh IVF
      cycles was 42.5%. When pregnancies arising from the transfer of thawed
      cryopreserved embryos were included, the cumulative ongoing pregnancy rate
      increased to 43.8%, rising to 44.8% when extrapolated data from as yet unthawed
      embryos was included. CONCLUSIONS: When analyzed in these terms, the
      supplementary benefit of cryopreserving supranumerical embryos appears limited.

PMID- 12503889
TI  - Variable expression of oviductin mRNA at different stages of human reproductive
      cycle.
AB  - PURPOSE: To examine the in vivo expression of oviductin mRNA at different stages
      of the human female reproductive cycle including pregnancy and after menopause.
      METHODS: Oviducts were obtained from 25 women in normal menstrual cycle, 5 in
      early pregnancy, 5 undergoing postpartum sterilization, and 4 menopausal women.
      The oviductal mucosal tissue was isolated and oviductin mRNA was assessed using
      reverse-transriptase-polymerase chain reaction (RT-PCR); its correlation with
      various hormones was assessed. RESULTS: Oviductin mRNA was detected throughout
      the menstrual cycle, highest in the periovulatory period. It continued to be
      expressed in early pregnancy but was absent in the postpartum period and after
      menopause. CONCLUSIONS: The production and function of oviductin at different
      stages of human reproductive cycle including pregnancy is not well known. Its
      highest expression at the time of ovulation is consistent with a supportive role
      in fertilization and early embryo development.

PMID- 12503890
TI  - Cyclooxygenase (COX)-2 and granulosa cell apoptosis in vitro.
AB  - PURPOSE: C-myc was studied in cyclooxygenase (COX)-2 associated granulosa cell
      apoptosis, METHODS: Granulosa cells (N = 5 cases) were incubated for 24 h in
      either 1 or 50 microM COX-2 inhibitor, 1 or 50 microM COX-1/COX-2 inhibitor,
      negative or positive controls Single primer polymerase chain reaction of c-myc
      exon 1 were performed. Bisbenzimide-stained control single-stranded (ssDNA) were
      hybridized to SYBR Gold-stained ssDNA and fluorescent images analyzed. RESULTS: C
      myc was disrupted by the high-dose COX-2 inhibitor. Cell viability decreased with
      COX-1 and COX-2 inhibition. However, cell viability was similar for the positive
      control and at low-dose COX-2 inhibition. CONCLUSIONS: Inhibition of both COX-1
      and COX-2 initiated apoptosis without disrupting c-myc suggesting a protective
      effect on c-myc. The low dosage of the COX-2 inhibitor did not disrupt c-myc and
      cell viability. C-myc sensitization was not part of apoptosis.

PMID- 12503891
TI  - Characterization of normal and polycystic ovaries using three-dimensional power
      Doppler ultrasonography.
AB  - PURPOSE: To evaluate the characteristics of polycystic compared to normal ovaries
      using three-dimensional (3-D) power Doppler ultrasonography. METHODS: We
      recruited 42 volunteers, all of whom were commencing IVF treatment. Each patient
      was examined in the cycle preceeding the start of drug therapy during the late
      follicular phase. If eight or more subcapsular follicles of 2-8 mm in diameter in
      one two-dimensional (2-D) plane were detected in either of the ovaries, the
      patient was categorized as having polycystic ovaries (PCO); otherwise the ovaries
      were considered normal. The parameters examined were volume of the ovary,
      vascularization index (VI), flow index (FI), vascularization flow index (VFI),
      and mean greyness (MG). In addition, the ovary was arbitrarily divided into
      cortex and stroma, and thereafter volume, VI, FI, VFI, and MG were calculated for
      these two regions. RESULTS: Twenty-eight women had normal ovaries and 14 had PCO.
      The comparison between normal and PCO showed that as a group the PCO were larger,
      without any differences in VI, Fl, VFI, or MG. In patients with PCO, the right
      ovary was larger than the left one. In patients with normal ovaries, Fl was
      higher on the left side. Division into cortex and stroma revealed that there were
      no differences in cortical or stromal VI, FI, VFI, or MG between normal and PCO
      on either side. CONCLUSIONS: The ovaries defined as polycystic were larger than
      normal ovaries, but there was no difference in the echogenicity of the stroma
      between polycystic and normal ovaries. We were also unable to demonstrate that
      the polycystic ovarian stroma was more vascularized than the stroma in the normal
      ovaries.

PMID- 12503892
TI  - Anti-macrophage inhibitory factor antibody inhibits PMSG-hCG-induced follicular
      growth and ovulation in mice.
AB  - PURPOSE: To investigate the effect of an anti-MIF antibody on PMSG-hCG-induced
      murine follicular growth and ovulation and to determine whether MIF plays an
      essential role in this process. METHODS: Mice were primed with an intraperitoneal
      injection of pregnant mare serum gonadotropin (PMSG) and were treated with an
      anti-rat MIF antibody and human chorionic gonadotropin (hCG) to induce ovulation.
      After that, the ovulated ova were counted. The ovaries were studied using
      standard histological procedures. RESULTS: Ovaries treated with the anti-MIF
      antibody showed reduced numbers of growing follicles surrounded by granulosa
      cells and theca cells with a little proliferation compared with the control. The
      average numbers of ova collected from mice treated with the anti-MIF antibody
      were reduced compared with those collected from control mice. CONCLUSIONS: Anti
      MIF antibody inhibits the follicular growth and ovulation in mice, and MIF may
      play an important role in the inflammatory reactions during follicle growth and
      ovulation.

PMID- 12503893
TI  - It's dead ... it doesn't work anymore, but will it get better?

PMID- 12503894
TI  - Experiences of the generalist nurse caring for adolescents with mental health
      problems.
AB  - Mental healthcare for adolescents is currently provided in a range of settings,
      including general hospital wards and paediatric wards, although care of
      adolescents with mental health problems in general settings has not been
      evaluated. This descriptive study surveyed generalist nurses who provide care to
      adolescents with mental health problems in the general hospital setting to
      determine satisfaction with their abilities to provide care, challenges
      encountered in care provision and strategies to provide optimal care by these
      nurses. Participants included 30 generalist nurses (response rate of 73%) from
      two wards in a tertiary paediatric hospital in Queensland, Australia. The survey
      findings showed that 67 percent of the respondents felt inadequately prepared to
      care for this group and only 41 percent were satisfied with their ability to
      provide care. Strategies identified to improve nursing care included: enhancement
      of continuity of care and teamwork, provision of appropriate environmental
      facilities, greater support from specialist mental health nurses and further
      education on caring for adolescent mental health problems.

PMID- 12503895
TI  - Parents' needs for knowledge concerning the medical diagnosis of their children.
AB  - It is reported that parents can handle their reactions of having a child with a
      chronic illness by seeking information and gaining knowledge about the diagnosis.
      It has been suggested that this is a way for parents to restore order in a
      chaotic existence. A complement to this perspective is to focus on what it means
      to be a parent and what is included in parenthood. The purpose of the present
      study was to increase our understanding of parents' need for knowledge.
      Interviews were conducted with parents (n = 44) who have experienced receiving a
      diagnosis of Turner Syndrome (TS) for their daughter, in order to explore the
      parents' motives and strategies for seeking information about the condition. Out
      of the 44 parents interviewed, 26 (21 mothers and 5 fathers) had sought
      information. It was found that the motives for seeking information were, to some
      extent, related to the parents' experiences of the consultation at the time of
      diagnosis. Twenty-three parents (21 mothers and 2 fathers) were dissatisfied with
      the information provided by the physician, while 21 (12 mothers and 9 fathers)
      were satisfied. Among the dissatisfied parents 16 (15 mothers and 1 father)
      sought information, and among the satisfied 10 parents (6 mothers and 4 fathers)
      sought information when they received the diagnosis for their daughter. The
      mothers described different strategies to gain information. They attended the
      library to borrow medical literature, looked up the syndrome in reference books,
      read articles in newspapers and asked questions of other mothers who had
      daughters with TS. However, it was found that the dissatisfied mothers used more
      and different strategies to find information compared with the fathers and the
      mothers who were satisfied. The motives of all the parents were to learn more
      about the condition. However, the dissatisfied mothers reported that they sought
      information because they found it important to control the actions of the
      professionals. The mothers that were satisfied with the information argued that
      they sought information in order to be able to explain the condition to others.

PMID- 12503896
TI  - Circumcision: a consideration of some of the controversy.
AB  - This article considers the procedure known as male circumcision. This is
      practised throughout the world for a variety of reasons, including medically
      essential reasons, health promotion, health protection, cultural, religious and
      aesthetic. It has been estimated that approximately one-third of the male
      population has been circumcized. As with some other surgical interventions its
      use is controversial, and there are a number of ethical and moral issues that are
      of interest to the children's nurse. The anatomy and physiology of the prepuce is
      summarized and the practice of circumcision and some of the risks and proposed
      benefits of the procedure are considered. This article is intended to be
      culturally sensitive and it is hoped that it will inform others and provoke
      discussion. It may enable the children's nurse to raise awareness of the issues
      among the general population.

PMID- 12503897
TI  - Ecotoxicological implications of aquatic disposal of coal combustion residues in
      the United States: a review.
AB  - We provide an overview of research related to environmental effects of disposal
      of coal combustion residues (CCR) in sites in the United States. Our focus is on
      aspects of CCR that have the potential to negatively influence aquatic organisms
      and the health of aquatic ecosystems. We identify major issues of concern, as
      well as areas in need of further investigation. Intentional or accidental release
      of CCR into aquatic systems has generally been associated with deleterious
      environmental effects. A large number of metals and trace elements are present in
      CCR, some of which are rapidly accumulated to high concentrations by aquatic
      organisms. Moreover, a variety of biological responses have been observed in
      organisms following exposure to and accumulation of CCR-related contaminants. In
      some vertebrates and invertebrates, CCR exposure has led to numerous
      histopathological, behavioral, and physiological (reproductive, energetic, and
      endocrinological) effects. Fish kills and extirpation of some fish species have
      been associated with CCR release, as have indirect effects on survival and growth
      of aquatic animals mediated by changes in resource abundance or quality. Recovery
      of CCR-impacted sites can be extremely slow due to continued cycling of
      contaminants within the system, even in sites that only received CCR effluents
      for short periods of time. The literature synthesis reveals important
      considerations for future investigations of CCR-impacted sites. Many studies have
      examined biological responses to CCR with respect to Se concentrations and
      accumulation because of teratogenic and reproductively toxic effects known to be
      associated with this element. However, the complex mixture of metals and trace
      elements characteristic of CCR suggests that biological assessments of many CCR
      contaminated habitats should examine a variety of inorganic compounds in
      sediments, water, and tissues before causation can be linked to individual CCR
      components. Most evaluations of effects of CCR in aquatic environments have
      focused on lentic systems and the populations of animals occupying them. Much
      less is known about CCR effects in lotic systems, in which the contaminants may
      be transported downstream, diluted or concentrated in downstream areas, and
      accumulated by more transient species. Although some research has examined
      accumulation and effects of contaminants on terrestrial and avian species that
      visit CCR-impacted aquatic sites, more extensive research is also needed in this
      area. Effects in terrestrial or semiaquatic species range from accumulation and
      maternal transfer of elements to complete recruitment failure, suggesting that
      CCR effects need to be examined both within and outside of the aquatic habitats
      into which CCR is released. Requiring special attention are waterfowl and
      amphibians that use CCR-contaminated sites during specific seasons or life stages
      and are highly dependent on aquatic habitat quality during those periods. Whether
      accidentally discharged into natural aquatic systems or present in impoundments
      that attract wildlife, CCR appears to present significant risks to aquatic and
      semiaquatic organisms. Effects may be as subtle as changes in physiology or as
      drastic as extirpation of entire populations. When examined as a whole, research
      on responses of aquatic organisms to CCR suggests that reducing the use of
      disposal methods that include an aquatic slurry phase may alleviate some
      environmental risks associated with the waste products.

PMID- 12503898
TI  - Air pollution in Athens basin and health risk assessment.
AB  - An inventory of air pollution sources within the Athens basin is carried out for
      the years 1989, 1992 and 1998 and the results are inputted in a climatological
      model for predicting ambient concentrations. Despite of the significant growth in
      the number of road vehicles and the deteriorating traffic, the emissions and
      ambient concentrations of fine particulates, CO, NOx and VOC appear to remain
      reasonably constant over for the period 1989 to 1998, while these of SO2 and Pb
      are reduced, mainly due to the renewal of vehicle fleet, the use of catalytic
      technologies and the improved quality of the used fuel. The results further
      indicate that for CO, NOx and VOC the major source is road traffic, while for
      PM2.5 and SO2 both space heating and traffic share responsibility. The air
      pollutant concentrations monitored by the network of 11 stations are reviewed and
      statistics related to air quality guidelines are presented. As fine particulate
      levels are not monitored, approximate PM2.5 and PM10 concentrations are derived
      from black smoke ones on basis of experimentally determined conversion factors.
      The computed and monitored air pollution levels are compared and found in
      reasonable agreement. The results of the above analysis show that the levels of
      all 'classical' pollutants, with the exception of SO2 and Pb, exceed
      significantly the WHO guidelines and are thus expected to exert a significant
      health impact. The latter could be quantified in relation to the PM2.5 or PM10
      levels on the basis of risk assessment information developed by the World Health
      Organization (WHO). The results show that the existing levels of fine particle
      concentrations in Athens increase significantly the mortality and morbidity, and
      reduce the average longevity of the entire population from 1.3 to 1.7 years.

PMID- 12503899
TI  - Comparison of ozone levels between working days and weekends in Athens, Greece.
AB  - Athens has a major problem of ozone air pollution due to its climate which is
      dominated by hot and dry summers with intense sunshine. As a result there is a
      high violation of the air quality limits of ozone. By comparing ozone air
      pollution between weekdays and weekends it is possible to estimate the effect of
      the reduction of primary pollutants causing the formation of ozone on the levels
      of this pollutant. Thus it was estimated that while during the weekends the
      concentrations of the ozone precursors (nitrogen oxides and volatile organic
      compounds) were reduced by the order of 10-20%, the effect on ozone levels was
      lower.

PMID- 12503900
TI  - Correlates of stages of change for substance abuse among psychiatric outpatients.
AB  - Brief algorithms are used to determine stage of change; however, psychometric
      support in substance users other than smokers is minimal. The authors examined
      the reliability and validity of a self-report algorithm in a sample of 84 persons
      with both psychiatric and substance use disorders. A 1-week retest resulted in
      75% of persons being reassigned to the same stage. Compared with
      precontemplators, participants in the preparation stage reported higher problem
      recognition, steps taken toward change, cons of using, and benefits of quitting.
      The pros of using did not differ across stages. The action stage was marked by
      less frequent substance use and lower perceived costs of quitting. These results
      support the reliability and validity of staging algorithms in patients with
      comorbid disorders.

PMID- 12503901
TI  - Item response theory modeling of substance use: an index based on 10 drug
      categories.
AB  - This study examined the psychometric characteristics of an index of substance use
      involvement using item response theory. The sample consisted of 292 men and 140
      women who qualified for a Diagnostic and Statistical Manual of Mental Disorders
      (3rd ed., rev.; American Psychiatric Association, 1987) substance use disorder
      (SUD) diagnosis and 293 men and 445 women who did not qualify for a SUD
      diagnosis. The results indicated that men had a higher probability of endorsing
      substance use compared with women. The index significantly predicted health,
      psychiatric, and psychosocial disturbances as well as level of substance use
      behavior and severity of SUD after a 2-year follow-up. Finally, this index is a
      reliable and useful prognostic indicator of the risk for SUD and the medical and
      psychosocial sequelae of drug consumption.

PMID- 12503902
TI  - The URICA as a measure of motivation to change among treatment-seeking
      individuals with concurrent alcohol and cocaine problems.
AB  - The original 4-factor structure of the University of Rhode Island Change
      Assessment (URICA; C. C. DiClemente & S. O. Hughes, 1990) was replicated, and the
      scale's internal consistency was found to be acceptable in a sample of 106
      cocaine- and alcohol-dependent participants receiving either disulfiram or no
      medication in a psychotherapy trial. In addition, participants categorized as
      having high Committed Action (CA), a new URICA composite, had a significantly
      greater percentage of days abstinent from both alcohol and cocaine (85.6%) than
      low-CA participants (72.7%, p < .01). Furthermore, a significant Treatment x CA
      interaction emerged, suggesting that low-CA participants had better outcomes than
      those with high CA when assigned to medication, whereas high-CA participants
      fared equally well with or without medication.

PMID- 12503903
TI  - Genes, environment, and individual differences in alcohol expectancies among
      female adolescents and young adults.
AB  - Alcohol expectancies are an important proximal causal risk factor in several
      models of the familial transmission of alcohol use, abuse, and dependence, yet
      the familial transmission of alcohol expectancies is not well understood. The
      purpose of this study was to examine the familial transmission of positive
      alcohol expectancies. Participants were 2,627 14- to 22-year-old female twins.
      Experiences shared by twins, rather than genetic factors, explained most of the
      familial similarity for positive alcohol expectancies, but an even larger
      proportion of the variation in positive alcohol expectancies was explained by
      nonfamilial factors. The extent to which the familial similarity for positive
      alcohol expectancies was moderated by age, race, drinking status, and the sharing
      of peer groups was also examined.

PMID- 12503904
TI  - Desired image of power, alcohol expectancies, and alcohol-related aggression.
AB  - Three hundred thirty-nine college students were surveyed regarding their usual
      drinking behavior, alcohol expectancies, desired identity of power, and
      experience with alcohol-related violence. Eight percent indicated having been in
      a fight in a bar, and 16% indicated having been in a fight while drinking in the
      previous year. Male heavy drinkers were more likely than female heavy drinkers to
      experience alcohol-related and bar violence. The belief that intoxication causes
      one to become aggressive was related to experiencing alcohol-related violence.
      However, the relationship of alcohol expectancies to alcohol-related aggression
      was moderated by an individual difference in the desire to be seen as powerful.
      Results are discussed in terms of cognitive models of alcohol expectancy
      development and maintenance.

PMID- 12503905
TI  - Attention biases and disinhibited behavior as predictors of alcohol use and
      enhancement reasons for drinking.
AB  - Disinhibition is a risk factor for alcohol use that may be specifically linked to
      drinking to enhance positive affect (enhancement motives). In this study
      individual differences germane to disinhibition were assessed, and their relation
      to alcohol use and reasons for drinking was examined. Laboratory tasks assessed
      attentional biases for reward and punishment cues and disinhibited behavior. Self
      reported personality, alcohol use, and reasons for drinking were included.
      Frequent alcohol use and frequent drinking for enhancement, but not for coping or
      social reasons, were associated with a bias to attend to reward cues and
      disinhibited behavior. Poor inhibitory control assessed by self-reports was also
      associated with alcohol use and enhancement reasons for drinking. Results support
      a positive reinforcement mechanism of alcohol use.

PMID- 12503906
TI  - Depressive symptoms among amphetamine and cocaine users before and after
      substance abuse treatment.
AB  - This study examined whether higher rates of depressive symptoms among amphetamine
      compared with cocaine users result from amphetamine use itself, polydrug use, or
      experiencing a major lifetime depressive episode and whether depressive symptoms
      among amphetamine users are more likely to persist 12 months after treatment. The
      association between amphetamine use and depressive symptoms disappears when
      controlling for polydrug use and lifetime major depressive episode. Polydrug use
      and lifetime depressive episode are significantly related to depressive symptoms
      in the year preceding treatment. Amphetamine use at intake does not predict
      depressive symptoms among individuals who are abstinent at follow-up, and
      amphetamine users are no more likely than cocaine users to report depression at a
      12-month follow-up.

PMID- 12503907
TI  - Relationship among gender, depression, and needle sharing in a sample of
      injection drug users.
AB  - The authors explored the relationships among gender, needle sharing, and
      depression in a sample of 392 male and 121 female street drug users. Using the
      Risk Behavior Assessment (National Institute on Drug Abuse, 1991) and the Beck
      Depression Inventory-2 (A. T. Beck, R. A. Steer, & G. K. Brown, 1996), the
      authors found that women reported higher levels of depression than men and that
      sharers endorsed higher levels of depression than nonsharers. Further, the
      authors found that female sharers reported the highest levels of depression of
      all groups, that is, as compared with male sharers, female nonsharers, and male
      nonsharers, who did not differ from one another. This suggests the presence of a
      special dynamic between gender and depression that is related to higher rates of
      needle sharing among women.

PMID- 12503908
TI  - Situations and moods associated with smoking in everyday life.
AB  - On 4 days, in everyday situations, 21 female and 26 male smokers used an
      electronic diary to record situations and moods at times of smoking and at
      control nonsmoking occasions. Self-reports of particular locations, activities,
      posture, consumption, social context, moods, and internal states were
      specifically associated with smoking. Real-time assessments in everyday
      situations provide useful information about the interplay of environmental
      factors and internal states in smoking. The findings suggest that conditioning
      and learning processes play a role in smoking and should be considered in smoking
      cessation programs.

PMID- 12503909
TI  - An investigation of predictors of nicotine abstinence in a smoking cessation
      treatment study of smokers with a past history of alcohol dependence.
AB  - This study investigated predictors for smoking abstinence at 12-week follow-up
      among 85 smokers with a past history of alcohol dependence enrolled in a smoking
      cessation trial. Length of alcohol abstinence at time of enrollment and longest
      previous period of smoking abstinence were significantly associated with smoking
      status at follow-up. Multiple logistic regression with these variables entered as
      predictors suggested that longest previous period of smoking abstinence partially
      mediated the relationship between length of alcohol abstinence at enrollment and
      smoking status at follow-up. Additional research is warranted to identify
      predictors of nicotine abstinence and smoking relapse in this population and to
      understand the factors that mediate the relationship between length of alcohol
      abstinence at enrollment and smoking outcome.

PMID- 12503910
TI  - Nature and origin of multicomponent aerial emissions of the copper-nickel smelter
      complex.
AB  - The Severonickel Smelter Complex as well as other big nickel-copper smelter
      plants are the source of metallurgical dust emissions, enriched with toxic
      elements Ni, Cu, Pb, Zn and As. The phase composition of typical metallurgy dust
      is described as pentlandite (Ni,Fe)9S8, pyrrhotite Fe7S8(Ni(x)), chalcopyrite
      CuFeS2, chalcosite Cu2S, covellite CuS, cuprite Cu2O, tenorite CuO, and metal
      copper and nickel. The fine dust fractions are enriched by lead, zinc and arsenic
      oxides. The obtained data can be turned to account when conducting the
      investigations of heavy metal behaviour in nature media, in particular soils.

PMID- 12503911
TI  - Removal of NOM in the different stages of the water treatment process.
AB  - Natural organic matter (NOM) is abundant in natural waters in Finland and in many
      ways affects the unit operations in water purification. In this study, the
      organic matter content in water in different stages of a full-scale treatment
      process over 1 year was measured. The full-scale treatment sequence, studied at
      the Rusko water treatment plant in Tampere, Finland, consisted of coagulation,
      flocculation, clarification by sedimentation or flotation, activated carbon (AC)
      filtration, and disinfection. High-performance size exclusion chromatography
      (HPSEC) was used for separation to determine changes in the humic substances
      content during the purification process. In addition, total organic carbon (TOC),
      KMnO4-number, and UV-absorbance at wavelength 254 nm (UV254) were measured. High
      molecular weight (HMW) matter was clearly easier to remove in coagulation and
      clarification than low molecular weight (LMW) matter. Furthermore, depending on
      the regeneration of the activated carbon filters, activated carbon filtration was
      effective to a degree but did not remove most of the lowest molecular weight
      compounds. Significant correlation was established among HPSEC, KMnO4, UV254
      absorbance, and TOC. HPSEC proved to be a fast and relatively easy method to
      estimate NOM content in water and, in fact, gave more information than
      traditional methods on the type of NOM in a water sample. It also helped the
      process performance follow-up.

PMID- 12503912
TI  - Concentrations of Cu and Pb in the offshore and intertidal sediments of the west
      coast of Peninsular Malaysia.
AB  - Malaysia is now a developing country and on her way towards being an
      industrialised one by the year 2020. Most of her industries and urban areas are
      located on the west coast of Peninsular Malaysia. In addition, the offshore area
      of the west coast is now one of the busiest shipping lanes in the world. These
      two phenomena make the intertidal and offshore areas of the west coast of
      Peninsular Malaysia interesting for scientific studies. Therefore, this study
      focused on both the offshore and intertidal sediments of the west coast of
      Peninsular Malaysia. Sampling for sediment samples were done from the northern to
      the southern ends of the peninsula and these sediment samples were analysed for
      Cu and Pb. It was found that total Cu concentrations ranged from 0.25 to 13.8 and
      0.40 to 315 microg/g dry weight (dw) for offshore and intertidal sediments,
      respectively. For Pb, it ranged from 3.59 to 25.4 and 0.96 to 69.8 microg/g dw
      for the offshore and intertidal sediments, respectively. The ranges of Cu and Pb
      found from the west coast of Peninsular Malaysia were low in comparison to
      regional data. However, some intertidal areas were identified as receiving
      anthropogenic Cu and Pb. Geochemical studies revealed that the 'nonresistant'
      fraction for Pb contributed about 70.0% to 75.0% and 54.0% of the total Pb
      concentration in the offshore and intertidal sediments, respectively. As for Cu,
      the 'nonresistant' fraction contributed about 46.2% to 60.4% and 46.3% of the
      total Cu concentration in the offshore and intertidal sediments, respectively.
      The 'nonresistant' fraction contained mostly of anthropogenic metals besides
      natural origins. These 'nonresistant' percentages indicated that both the
      offshore and intertidal areas could have received anthropogenic-derived metals,
      which could be influenced by physico-chemical properties of the sediments.
      Although the present data indicated that contamination due to Cu and Pb in the
      west coast of Peninsular Malaysia especially in the offshore areas were not
      serious, regular biomonitoring studies along the west coast of Peninsular
      Malaysia are recommended.

PMID- 12503913
TI  - Post-irrigation impact of domestic sewage effluent on composition of soils, crops
      and ground water--a case study.
AB  - Long-term irrigation with sewage water adds large amounts of carbon, major and
      micro- nutrients to the soil. We compared the spatial distribution of N, P, K and
      other micronutrients and toxic elements in the top 0.6 m of an alluvial soil
      along with their associated effects on the composition of crops and ground waters
      after about three decades of irrigation with domestic sewage effluent as a
      function of distance from the disposal point. Use of sewage for irrigation in
      various proportions improved the organic matter to 1.24-1.78% and fertility
      status of soils especially down to a distance of 1 km along the disposal channel.
      Build up in total N was up to 2908 kg ha(-1), available P (58 kg ha(-1)), total P
      (2115 kg ha(-1)), available K (305 kg ha(-1)) and total K (4712 kg ha(-1)) in
      surface 0.15 m soil. Vertical distribution of these parameters also varied, with
      most accumulations occurring in surface 0.3 m. Traces of NO3-N (up to 2.8 mg l(
      1)), Pb (up to 0.35 mg l(-1)) and Mn (up to 0.23 mg l(-1)) could also be observed
      in well waters near the disposal point thus indicating initiation of ground water
      contamination. However, the contents of heavy metals in crops sampled from the
      area were below the permissible critical levels. Though the study confirms that
      the domestic sewage can effectively increase water resource for irrigation but
      there is a need for continuous monitoring of the concentrations of potentially
      toxic elements in soil, plants and ground water.

PMID- 12503914
TI  - Presence of erm genes among macrolide-resistant Gram-positive bacteria isolated
      from Danish farm soil.
AB  - The presence of erm genes was investigated among macrolide-resistant Gram
      positive bacteria isolated from soil samples collected from four Danish farms
      that had been treated with animal waste. Soil samples were collected before, a
      few days after spread and 1 1/2 months and 5 months later. In 33% (9/27) of these
      isolates, an erm gene was detected using PCR. Eight isolates were positive for
      erm(B) and one isolate was positive for erm(C). No isolates contained erm(A),
      erm(D) or erm(F). The positive isolates were identified to genus level. Two
      erm(B) positive isolates were identified as Enterococcus spp., and the erm(C)
      positive isolate as a Streptococcus spp., probably indicating survival from
      animal waste. The remaining six erm(B) positive isolates all belonged to the
      Bacillus cereus group. The erm(B) gene has not previously been identified in B.
      cereus but is frequently found among enterococci. This result could indicate
      horizontal transfer from bacteria of animal origin to indigenous soil bacteria.

PMID- 12503915
TI  - Cadmium desorption in sand.
AB  - Desorption of cadmium (Cd) from sand was studied by both batch and flow-through
      methods. Batch experiments were conducted at three pH values (5.5, 6.0 and 6.5).
      In each case, the amount of Cd desorbed was low compared with the quantity of Cd
      adsorbed previously. Desorption of Cd in the batch experiments can be described
      adequately by a Freundlich isotherm. The Freundlich isotherm coefficient, Kf,
      increased with pH. Hysteresis between the sorption/desorption isotherms was
      observed in all batch experiments. Flow-through experiments in soil columns were
      conducted for the same three pH values, with the results used to determine
      transport and sorption/desorption parameters. Again, the desorption isotherms
      bore little resemblance to the corresponding adsorption isotherms. The
      experimental breakthrough curves were well fitted by a nonequilibrium desorption
      model, however the time scale of the desorption process was much larger than
      measured in batch experiments. This model was therefore rejected as lacking
      realism. A simple linear retardation (including hysteresis) model that utilises
      different isotherms was found to simulate column breakthrough curves well. The
      Freundlich isotherm coefficients, Kf, in all batch and flow-through desorption
      experiments were different to values evaluated from the corresponding adsorption
      experiments. However, in contrast to adsorption, desorption in flow-through
      experiments was not noticeably affected by changes in pH. The effect of pore
      water velocity on desorption was also studied at pH 6.0. No trend was established
      between flow velocity and the desorption coefficient.

PMID- 12503916
TI  - A preliminary study of ozone trend and its impact on environment in Hong Kong.
AB  - As far as the impact of air pollutants on human health being is concerned, ozone
      (O3) is one of the most pollutant sources, and, in particular, the ground level
      ozone is responsible for a variety of adverse effects on both human being and
      plant life. To protect the population from such adverse health effects, early
      information and precautions about the high ozone level need to be ascertained. In
      this study, statistical characteristics of ground level ozone is analyzed
      according to field monitoring data in mixed residential, commercial and
      industrial areas, e.g., Tsuen Wan area in Hong Kong. The study deals with the
      characteristics of hourly and daily mean ozone levels under different climatic
      conditions such as temperature, solar radiation (SR), wind speed (WS), and other
      pollutant concentration levels. The study aims to investigate the importance of
      meteorological factors and their impact on relevant pollutant concentration
      levels from a chemical aspect. Further, reasons for the spatial and temporal
      variation of ozone levels are discussed. All these results will provide a
      physical basis for accurately predicting ozone concentration in similar research.

PMID- 12503917
TI  - Cypress tree (Cupressus semervirens L.) bark as an indicator for heavy metal
      pollution in the atmosphere of Amman City, Jordan.
AB  - Bio-monitoring of air quality in Amman City was investigated by analyzing 36
      cypress tree (Cupressus semervirens L.) bark samples from three sites of
      different anthropogenic activities at the end of summer season 2001. Cypress
      barks were found to be a good bio-indicator for air pollution in arid regions.
      Variation in Pb, Zn, Mn, Cr, Ni, Cd, and Cu contents between sites was observed
      due to different types of activities. Traffic emissions were found to be the main
      source of heavy metal pollution in the atmosphere of Amman. Lead content was
      found to be the highest in highly traffic density areas. The industrial part of
      the city was characterized by high Zn, Mn, Cr, Ni, and Co contents. No
      significance variations were found in pH values of the bark between the sites.
      This was attributed to buffering effect of carbonate in the atmosphere originated
      from soil of the area.

PMID- 12503918
TI  - Trace determination of caffeine in surface water samples by liquid chromatography
      -atmospheric pressure chemical ionization--mass spectrometry (LC-APCI-MS).
AB  - A new method based on liquid-liquid extraction (LLE) coupled to reverse phase
      liquid chromatography and atmospheric pressure chemical ionization mass
      spectrometry (LC-APCI-MS) has been applied to determine trace amounts of caffeine
      (1,3,7-trimethylxanthine) in surface water samples from a near coastal ecosystem
      such as Biscayne Bay, Florida. The rational behind the development of such method
      will be to evaluate the use of unmetabolized caffeine as a potential dissolved
      phase tracer of human waste contamination. The method allows for the
      determination of caffeine at levels as low as 4.0 ng/l (ppt) in both salt and
      freshwater by extracting and concentrating a 1-1 water sample to a final volume
      of 500 microl and using HPLC separation coupled to an atmospheric pressure
      chemical ionization mass spectrometry (APCI-MS) system operated in selected ion
      monitoring (SIM) for the protonated molecular ions (M + H(+)). Samples from
      different portions of Biscayne Bay and the Miami River, one of its major
      tributaries, were analyzed and caffeine was detected in those areas previously
      identified for consistently exceeding the water quality criteria for fecal
      coliform bacteria contamination. The caffeine concentration in the samples with
      positive detection was generally low at levels equal or lower than 41 ng/l.
      However, there is a marked difference between samples collected in open bay areas
      and those collected from the Miami River.

PMID- 12503919
TI  - Environmental risk assessment and the intrusion of bias.
AB  - The concept of managing the environment and any associated human health impacts
      by means of such science-based tools as toxicological evaluation, risk
      assessment, and economic appraisal has become widely accepted in professional
      circles. These increasingly complex methodologies have not won universal support,
      however, even among the technically minded, and the wider public has in many
      cases remained sceptical. The public's seeming lack of enthusiasm has frequently
      been assigned to ignorance of science, irrationality even, and some attempts have
      been made to ameliorate the situation by means of education, though with little
      evidence of success. However, this review advances an alternative explanation,
      namely, that the disenchantment has more to do with procedural than technical
      matters. Many issues, although treated with technical risk assessment appear to
      have forced themselves onto the agenda because of factors only passingly
      connected with risk, and which are more related to the intrusion of disputed
      values and other sources of bias. This paper also notes that the intervention of
      bias in decision making is rife, and is found as much in professional as in
      public approaches. This need not itself be a problem, providing it is recognised
      and openly expressed. However, there remains a need for much greater
      circumspection and frankness by professions about the status of their art, and a
      determined effort if the full social benefits of environmental risk assessment
      (ERA) are to be realised.

PMID- 12503920
TI  - Occurrence and fate of hormone steroids in the environment.
AB  - Hormone steroids are a group of endocrine disruptors, which are excreted by
      humans and animals. In this paper, we briefly review the current knowledge on the
      fate of these steroids in the environment. Natural estrogenic steroids estrone
      (E1), 17beta-estradiol (E2) and estriol (E3) all have a solubility of
      approximately 13 mg/l, whereas synthetic steroids 17alpha-ethynylestradiol (EE2)
      and mestranol (MeEE2) have a solubility of 4.8 and 0.3 mg/l, respectively. These
      steroids have a moderate binding on sediments and are reported to degrade rapidly
      in soil and water. Estrogenic steroids have been detected in effluents of sewage
      treatment plants (STPs) in different countries at concentrations ranging up to 70
      ng/l for E1, 64 ng/l for E2, 18 ng/l for E3 and 42 ng/l for EE2. E2
      concentrations in river waters from Japan, Germany, Italy and the Netherlands
      ranged up to 27 ng/l. In addition, E2 concentrations ranging from 6 to 66 ng/l
      have also been measured in mantled karst aquifers in northwest Arkansas. This
      contamination of ground water has been associated with poultry litter and cattle
      manure waste applied on the land. Although hormone steroids have been detected at
      a number of sources worldwide, currently, there is limited data on the
      environmental behaviour and fate of these hormone steroids in different
      environmental media. Consequently, the exposure and risk associated with these
      chemicals are not adequately understood.

PMID- 12503921
TI  - Research at the Veterans Affairs Rehabilitation Research and Development National
      Center for Rehabilitative Auditory Research.

PMID- 12503922
TI  - Assessment of patients for treatment with tinnitus retraining therapy.
AB  - Clinical management for patients complaining of severe tinnitus has improved
      dramatically in the last 25 years. During that period of time, various methods of
      treatment have been introduced and are being used with varying degrees of
      success. One method that has received considerable attention is tinnitus
      retraining therapy (TRT). This method is being practiced by hundreds of
      clinicians worldwide, and retrospective clinical data indicate that TRT has been
      effective for the majority of patients. This article provides a guide for
      clinicians to evaluate their patients for treatment with TRT. Included in this
      guide is the expanded version of the TRT initial interview and specific
      instructions for the clinician administering the interview.

PMID- 12503923
TI  - Assessment and treatment of tinnitus patients using a "masking approach.".
AB  - Audiology clinics are increasingly being asked to provide tinnitus treatment
      services to patients who are severely distressed by tinnitus. It is unclear what
      levels of tinnitus care are available at different audiology clinics across the
      nation. Some clinics have staff who are experienced with the tinnitus masking
      technique or with tinnitus retraining therapy (TRT), whereas other clinics may
      limit their care to the provision of hearing aids. This article is an attempt to
      provide some basic information for those clinicians who would like to provide at
      least a minimum level of care for their tinnitus patients using the tinnitus
      masking approach. The most important requirement is a commitment by the clinician
      to assemble some basic resources and to structure the clinical schedule so that
      adequate time is available for historical review, evaluation, trial and selection
      of devices, and tinnitus counseling. A minimum set of measurements is recommended
      for inclusion in the tinnitus evaluation process. This informal review summarizes
      a variety of clinical observations culled from years of direct patient care
      experience. A tinnitus questionnaire is provided to help clinicians review
      potentially relevant issues.

PMID- 12503924
TI  - Comparison of tinnitus masking and tinnitus retraining therapy.
AB  - Two methods for treating tinnitus are compared. Tinnitus masking has been used
      for over 25 years, and although this method is used in clinics around the world,
      there are many misconceptions regarding the proper protocol for its clinical
      application. Tinnitus retraining therapy has been used clinically for over 12
      years and has received considerable international attention. Although these
      methods are distinctive in their basic approach to tinnitus management, certain
      aspects of treatment appear similar. These aspects of treatment have created
      considerableconfusion and controversy, especially regarding the use of "sound
      therapy" as a basic component of treatment. It is the objective of this article
      to clarify the major differences that exist between these two forms of treatment.

PMID- 12503925
TI  - Adverse drug events associated with hospital admission.
AB  - OBJECTIVE: To increase the knowledge base on the frequency, causality, and
      avoidability of adverse drug events (ADEs) as a cause for admission in internal
      medicine or when occurring during hospitalization. METHODS: A prospective study
      was performed for 6 periods of 8 days each. Epidemiologic data (e.g., age,
      gender, medical history), drug utilization, and adverse drug reactions on
      patients hospitalized during these periods were collected by a pharmacy student.
      RESULTS: A total of 156 patients (70 men and 86 women) were included in the
      study. The patients' mean age +/- SD was 66.5 +/- 18.1 years and mean length of
      stay was 13.2 +/- 9 days. Renal and hepatic insufficiency and previous history of
      drug intolerance were observed in 17.9%, 10.2%, and 2% of the hospitalized
      patients, respectively. Thirty-eight ADEs occurred in 32 patients; in 15 cases,
      ADEs were identified as the reason for admission, 10 cases occurred during
      hospitalization, and 13 cases were present at admission, but were not the cause
      of admission. The most frequent ADEs involved the neurologic (23.6%), renal
      (15.7%), and hematologic (13.1%) systems. Among these 38 ADEs, 22 were considered
      avoidable (57.9%); 20 of these were associated with therapeutic errors
      (inappropriate administration, drug-drug interactions, dosage error, drug not
      stopped despite the onset of ADEs). Patients with ADEs stayed longer in the
      hospital and took more drugs both before and during their hospital stay (p <
      0.05). CONCLUSIONS: Most of the ADEs observed in this study were avoidable. The
      risk/benefit ratio of administered drugs could be improved with better knowledge
      of the patients' medical history and the risk factors of ADEs.

PMID- 12503926
TI  - Concomitant coumarin-NSAID therapy and risk for bleeding.
AB  - OBJECTIVE: To investigate the risk of bleeding complications during the combined
      use of coumarin derivatives and nonsteroidal antiinflammatory drugs (NSAIDs)
      compared with the use of coumarin derivatives alone. SUBJECTS AND METHODS: In
      this 1-year observational study, the local outpatient anticoagulation office
      detected all coumarin users with bleeding complications. These patients were sent
      questionnaires regarding the type and consequences of the bleeding as well as
      previous NSAID use. The local pharmacists detected patients with concomitant
      coumarin and NSAID prescriptions (but no bleeding). The relative risk for
      bleeding due to concomitant coumarin and NSAID use was estimated. RESULTS: During
      1 year, 738 hemorrhages were identified in 681 coumarin users. In 12.2% of these
      cases, an NSAID was involved. In contrast, in the whole population of coumarin
      users, 2.5% were prescribed an NSAID. Therefore, the relative risk of NSAID use
      with regard to bleeding complications was 5.8 (95% CI 2.3 to 13.6). CONCLUSIONS:
      NSAID use during coumarin therapy considerably increases the bleeding risk
      compared with coumarin therapy alone. Although in daily practice these
      medications are frequently prescribed concomitantly, our results underscore the
      contraindication of concomitant use of NSAIDs and coumarin derivatives.

PMID- 12503927
TI  - Pain and distress from bone marrow aspirations and lumbar punctures.
AB  - OBJECTIVE: To compare the efficacy of 3 different pharmacologic regimens to
      relieve pain and distress in children with cancer undergoing bone marrow
      aspirations (BMAs) and lumbar punctures (LPs). DESIGN: Retrospective cohort study
      with crossovers for some patients. PATIENTS AND METHODS: The pain and distress
      ratings of patients undergoing BMAs (n = 73) and LPs (n = 105) were examined in a
      comparison of 3 different interventions: (1) a topical eutectic mixture of
      lidocaine and prilocaine (EMLA cream), (2) oral midazolam and EMLA cream, or (3)
      propofol/fentanyl general anesthesia. The choice of the intervention depended on
      patient/parent request. A validated faces pain scale was completed by the child
      or parent following each BMA or LP. The faces pain scale includes ratings of the
      severity of pain (from 0 = none to 5 = severe) and ratings of how frightened
      (from 0 = not scared to 5 = scared) the child was prior to each procedure.
      Comparisons of the pain and distress ratings were made among all patients for
      their first procedure and also within individual patients who had received >1 of
      the 3 interventions. Independent comparisons between the first treatments
      received by each patient were analyzed using Kruskal-Wallis tests. Comparisons of
      different crossover treatments received by individual patients were analyzed
      using Wilcoxon tests. RESULTS: For all first procedures, mean +/- SD pain and
      distress ratings during LPs were significantly lower when propofol/fentanyl was
      used (n = 43; 0.4 +/- 1.0 and 1.4 +/- 1.7) versus either EMLA (n = 29; 2.4 +/-
      1.7 and 2.9 +/- 1.9) or midazolam/EMLA (n = 33; 2.4 +/- 1.8 and 2.7 +/- 1.8),
      respectively. Pain and distress ratings during BMAs were also significantly lower
      with propofol/fentanyl (n = 29; 0.5 +/- 1.0 and 1.2 +/- 1.7) versus EMLA (n = 21;
      3.5 +/- 1.6 and 3.3 +/- 1.8) or midazolam/EMLA (n = 23; 3.3 +/- 1.5 and 3.0 +/-
      1.9), respectively. When data were analyzed within each patient, these
      differences were also present. CONCLUSIONS: Children receiving propofol/fentanyl
      general anesthesia experienced significantly less procedure-related pain and
      distress than did those receiving either EMLA or oral midazolam/EMLA.

PMID- 12503928
TI  - Comparison of two methods of delivering continuously nebulized albuterol.
AB  - OBJECTIVE: To compare the relative delivery of 2 methods for providing
      continuously nebulized albuterol (CNA): a small-volume nebulizer plus infusion
      pump versus a large-volume nebulizer. DESIGN: An open, randomized comparison of 3
      hours of CNA administration using an in vitro lung model with a follow-up
      particle size assessment of the large-volume nebulizer. METHODS: Six different
      nebulizers of each type were connected to a lung model via a volume-limited
      mechanical ventilator and infant ventilator circuitry. Albuterol was nebulized at
      10 mg/h for 3 hours in random order. The small-volume nebulizer used was the
      Airlife Misty Neb (Baxter, Valencia, CA); the large-volume nebulizer was the
      HEART Nebulizer (Vortran Medical, Orangevale, CA). One large-volume nebulizer was
      operated over 8 hours for the output and particle sizing study. RESULTS: The
      small-volume nebulizer delivered a greater amount of albuterol (mean +/- SD
      percentage of total nebulized) to the model lung (5.75 +/- 1.38% vs. 4.12 +/-
      0.67%; p < 0.025) than the large-volume nebulizer, but demonstrated greater
      variability. Although total output was not maintained after 8 hours of
      nebulization with the large-volume nebulizer, the percent of particles in the
      respirable range remained consistent. CONCLUSIONS: The large-volume nebulizer
      evaluated in this study maintains consistent output up to 8 hours and provides an
      acceptable method for delivering CNA through an infant ventilator circuit.

PMID- 12503929
TI  - Alteplase versus urokinase for occluded hemodialysis catheters.
AB  - BACKGROUND: The use of central venous catheters as a source of vascular access in
      patients undergoing hemodialysis may be complicated by thrombosis. Frequently,
      thrombolytics are used in an attempt to reestablish blood flow through partially
      or completely occluded catheters. OBJECTIVE: To compare the efficacy of alteplase
      (recombinant tissue plasminogen activator) versus urokinase in reestablishing
      adequate blood flow through partially or completely occluded vascular catheters.
      METHODS: Part 1 of the study prospectively investigated the effect of alteplase
      in reestablishing adequate blood flow through partially or completely occluded
      vascular catheters in 30 hemodialysis patients. Part 2 of the trial compared the
      efficacy of alteplase with that of urokinase in 14 of 30 patients who had also
      previously received urokinase. A 30-minute push-protocol was used to administer
      thrombolytics in both parts of the study. The primary endpoint was the proportion
      of patients with partially or completely occluded catheters achieving post
      thrombolytic blood flow of > or =200 mL/min. RESULTS: Part 1 showed a large
      proportion of partially or completely occluded catheters achieving post-alteplase
      blood flows > or =200 mL/min (70/76, 92.1% vs. 34/40, 85%, respectively). In Part
      2 of the study, the proportion of partially occluded catheters achieving post
      thrombolytic blood flows > or =200 mL/min was not significantly different between
      the alteplase and urokinase groups, (36/41, 87.8% vs. 21/28, 75%, respectively; p
      = 0.205). The proportion of completely occluded catheters achieving post
      thrombolytic blood flows > or =200 mL/min was significantly better with alteplase
      compared with urokinase (15/17, 88.2% vs. 6/14, 42.8%, respectively; p =.018).
      CONCLUSIONS: Alteplase, administered via the 30-minute push-protocol, is an
      effective thrombolytic for restoring hemodialysis catheter patency. In our study
      sample, alteplase was generally more effective than urokinase in restoring blood
      flow through catheters, especially those that were completely occluded.

PMID- 12503930
TI  - Relationship between patients' warfarin knowledge and anticoagulation control.
AB  - OBJECTIVE: To evaluate patients' knowledge of warfarin and its relationship to
      anticoagulation control. METHODS: From January to March 1999, 122 patients
      attending the warfarin clinic of the Prince of Wales Hospital in Hong Kong were
      interviewed. Their knowledge of warfarin therapy and adherence to medical advice
      were tested by 9 questions. A score (maximum 1.0) was calculated for each
      patient. The number of international normalized ratios (INRs) that was within the
      target range in the 4 most recent clinic visits was noted. RESULTS: Fifty-six men
      and 66 women participated in the study (mean +/- SD age 58.0 +/- 13.0, duration
      of treatment 43.1 +/- 39.8 mo). Patients' warfarin knowledge was poor, with an
      overall score of 0.48 +/- 0.18. Participants generally knew the colors of their
      warfarin tablets and took them regularly. They almost always informed their
      physicians and dentists of their warfarin therapy. Only 40-45% of patients knew
      the strengths of their warfarin tablets, the reason for taking warfarin, and its
      effect on the body. Their deficiencies in knowledge were even more obvious with
      respect to the possible consequences of under- or over-anticoagulation, drugs and
      medicated oils that might interact with warfarin, and management of a missed
      dose. Knowledge was related to age (r -0.43; p < 0.001) and duration of therapy
      (r 0.18; p = 0.044). Sixty patients (49.2%) had read the information booklet on
      warfarin and had better knowledge than those who had not (0.53 +/- 0.20 vs. 0.42
      +/- 0.20; p < 0.001). Illiteracy was the main reason for not reading the booklet.
      There was a positive correlation between patients' warfarin knowledge and the
      number of INR values that was within the target range in the 4 most recent clinic
      visits (r 0.20; p = 0.024). CONCLUSIONS: Patients' warfarin knowledge, a
      determinant of anticoagulation control, was generally poor. More attention should
      be given to the education of elderly and illiterate patients.

PMID- 12503931
TI  - Reliability of a modified medication appropriateness index in community
      pharmacies.
AB  - BACKGROUND: The medication appropriateness index (MAI) has demonstrated
      reliability in selected outpatient clinics where medical data were easily
      accessible from medical charts. However, its use in the community setting where
      patient data may be limited has not been examined. OBJECTIVE: To evaluate the
      usefulness of a modified MAI for use in the community pharmacy setting by testing
      interrater reliability using 3 different rating schemes. METHODS: Two raters
      evaluated 160 medications for 32 elderly ambulatory patients. Patient information
      was acquired using community pharmacist-collected medication histories. A
      summated MAI score, percent agreement, kappa, positive agreement, negative
      agreement, and intraclass correlation coefficient were calculated for each
      criterion using 3 scoring schemes. A paired samples t-test (95% CI) was used to
      test interrater reliability. RESULTS: The kappa statistics were >0.75 for
      indication and effectiveness, but good (0.41-0.66) for the remaining criteria
      using the Hanlon scoring scheme. The intraclass coefficients (0.82, 0.86, 0.87)
      and overall kappa (0.65, 0.66, 0.61) were similar for the 3 schemes. CONCLUSIONS:
      This study suggests that the modified MAI has the potential to detect medication
      appropriateness and inappropriateness in the community pharmacy setting; however,
      it is not without limitations. Because the MAI has the most clinimetric and
      psychometric data available, the instrument should be studied further to increase
      its reliability and generalizability.

PMID- 12503932
TI  - CANCER resistance surveillance program: initial results from hematology-oncology
      centers in North America. Chemotherapy Alliance for Neutropenics and the Control
      of Emerging Resistance.
AB  - OBJECTIVE: The CANCER (Chemotherapy Alliance for Neutropenics and the Control of
      Emerging Resistance) surveillance program was initiated to collect culture data
      on antimicrobial and antifungal agents in hospitals treating neutropenic patients
      in North America, as a means to monitor the development of microbial resistance.
      METHODS: A total of 2042 isolates from bloodstream, respiratory, urinary, and
      cutaneous infections in 2000-2001 were submitted by 33 oncology centers, clinics,
      and hospitals in North America, sent to a central laboratory, and tested by
      National Committee for Clinical Laboratory Standards methods against 42 different
      antimicrobials. RESULTS: Staphylococcus aureus, Escherichia coli, coagulase
      negative staphylococci, Enterococcus spp., and Klebsiella spp. represented the
      most frequently isolated pathogens during the initial benchmark year. The
      incidence of extended-spectrum beta-lactamase-producing phenotypes ranged from
      1.6% to 4.6% among E. coli and Klebsiella spp. Amikacin, tobramycin, polymyxin B,
      and piperacillin/tazobactam provided the highest susceptibility rates against
      Pseudomonas aeruginosa isolates. Yeast bloodstream isolates demonstrated complete
      susceptibility to amphotericin B, but 14% of strains were considered to have high
      level fluconazole resistance. CONCLUSIONS: Elevated resistance rates when
      compared to general hospital strains were not observed in the CANCER program
      during the baseline year of this novel longitudinal, resistance surveillance
      program. The prevalence of gram-positive pathogens, although representing more
      than 50% of all bacterial isolates, was slightly lower than that reported
      previously by other investigators. Continued evaluation for antimicrobial
      resistance as well as changes in the prevalence of gram-positive pathogens
      requires the use of longitudinal surveillance programs such as the CANCER
      program. Such initiatives allow the development of therapeutic strategies for
      coping with changes in resistance and pathogen prevalence in this dynamic at-risk
      patient environment.

PMID- 12503933
TI  - Fulminant liver failure associated with clarithromycin.
AB  - OBJECTIVE: To report a patient developing fulminant liver failure while being
      treated with clarithromycin for pneumonia. CASE SUMMARY: A 58-year-old white
      woman developed fulminant liver failure while being treated with the macrolide
      antibiotic clarithromycin for pneumonia. Comedication included N-acetylcysteine,
      atenolol, and isradipine. Other causes of liver failure, such as viral hepatitis,
      autoimmune hepatitis, toxins, and heart failure, were excluded by appropriate
      diagnostic means. All drugs were stopped, and the patient was transferred to
      another hospital for liver transplantation. She recovered spontaneously within
      several days, making transplantation unnecessary. A liver biopsy obtained 10 days
      after the initial presentation revealed centroacinar necrosis and beginning
      fibrous reorganization, compatible with recent centroacinar damage. DISCUSSION:
      Since no other cause could be identified, liver injury was considered to be drug
      related. Fulminant liver failure has not previously been described with
      concomitant use of atenolol and N-acetylcysteine. Although isradipine has been
      associated with hepatocellular injury, there are no reports of fulminant liver
      failure with this agent, and our patient had been treated for >2 years without
      signs of toxicity. The most likely cause of liver failure in this patient was,
      therefore, clarithromycin, which undergoes hepatic metabolism and has been
      reported to cause fulminant hepatic failure. A second possibility is an
      interaction between clarithromycin and isradipine, potentially increasing the
      hepatic toxicity of isradipine. CONCLUSIONS: Clarithromycin may be a cause of
      fulminant liver failure either alone or by inhibiting the metabolism of other
      drugs.

PMID- 12503934
TI  - Sensorineural hearing loss associated with intrathecal vancomycin.
AB  - OBJECTIVE: To report a case of nonreversible bilateral sensorineural hearing loss
      resulting from administration of intrathecal vancomycin. CASE SUMMARY: A 63-year
      old white man with newly diagnosed pre-B-cell acute lymphocytic leukemia
      developed Corynebacterium jeikeium meningitis associated with an Ommaya
      reservoir. The patient was treated with intravenous vancomycin for several days
      without symptomatic improvement, and intrathecal vancomycin was added to the
      treatment regimen. Difficulty in the patient's hearing was noted after the first
      intrathecal dose and he experienced complete hearing loss after the second
      intrathecal dose. An audiogram was performed and the patient was diagnosed with
      cranial nerve VIII bilateral sensorineural hearing loss. The Ommaya reservoir was
      removed and the patient was successfully treated with linezolid. DISCUSSION:
      Ototoxicity with intravenous vancomycin has been documented in multiple case
      reports, but this adverse effect has not been reported with intrathecal
      vancomycin. Cerebrospinal fluid vancomycin concentrations were not measured in
      our patient, but there was 1 documented occurrence of supratherapeutic serum
      vancomycin concentrations. Other drug-related causes of ototoxicity were
      evaluated and intrathecal vancomycin-induced ototoxicity was considered to be
      possible according to the Naranjo probability scale. CONCLUSIONS: The strong
      temporal relationship that was seen in this case suggests the possibility of an
      association between administration of intrathecal vancomycin and hearing loss.
      Healthcare providers should consider the potential for this adverse reaction with
      the intrathecal route of vancomycin administration.

PMID- 12503935
TI  - Lactic acidemia associated with metformin.
AB  - OBJECTIVE: To report 2 cases of lactic acidemia associated with the use of
      metformin in patients with normal renal function. CASE SUMMARY: An 82-year-old
      African American man and a 76-year-old white man developed an elevated serum
      lactic acid concentration a few weeks after initiation of metformin therapy for
      type 2 diabetes. After the patients discontinued metformin, the serum lactic acid
      concentration normalized in both cases. An objective causality assessment
      revealed that the adverse drug event was probably related to the use of
      metformin. DISCUSSION: Metformin interferes with the production and elimination
      of lactic acid by a variety of mechanisms that are not well understood. Few
      systematic data are available on changes in plasma lactic acid concentrations in
      patients with type 2 diabetes and normal renal function. Clinical significance of
      a high serum lactic acid concentration needs clarification. CONCLUSIONS:
      Metformin therapy can be associated with subclinical elevation of lactic acid
      concentration in the absence of renal insufficiency or other contraindications to
      using this agent in patients with type 2 diabetes. Periodic monitoring of basic
      metabolic panels may prevent this potentially serious complication of metformin
      therapy.

PMID- 12503936
TI  - Possible liposomal amphotericin B-induced nephrogenic diabetes insipidus.
AB  - OBJECTIVE: To report the development of nephrogenic diabetes insipidus (NDI)
      associated with the use of high-dose liposomal amphotericin B. CASE SUMMARY: A 38
      year-old white man with relapsed acute myelogenous leukemia underwent a matched
      unrelated donor allogeneic bone marrow transplant with adequate engraftment and
      mild graft-versus-host disease responding to corticosteroids. Approximately 11
      months after transplant, the patient was admitted to the hospital with suspected
      fungal pneumonia and started on liposomal amphotericin B (baseline serum
      creatinine 1.4-1.5 mg/dL). The dose was increased due to his immunosuppression
      and poor response, as the fungal etiology was identified as Torulopsis glabrata.
      The patient required mechanical ventilation due to biopsy-proven bronchiolitis
      olbiterans organizing pneumonia. Additionally, he developed diffuse alveolar
      hemorrhage and received intravenous desmopressin, with a reduction in bloody
      secretions. He also developed hypernatremia (serum sodium 155 mEq/L) on day 3 of
      the desmopressin and had an inappropriately increased urine output consistent
      with NDI. The most likely etiology for the NDI was liposomal amphotericin B and
      its associated hypokalemia. DISCUSSION: The observation of worsening
      hypernatremia (serum sodium increased from 135 to 164 mEq/L) with polyuria was
      associated with an increasing cumulative dosage of liposomal amphotericin B for
      fungal pneumonia despite the concurrent use of intravenous desmopressin.
      Aggressive water replacement was an effective treatment option in this patient.
      The Naranjo probability scale classified this as a possible adverse reaction
      because of the temporal sequence of NDI after high-dose liposomal amphotericin B
      and previously reported cases of NDI associated with amphotericin B
      desoxycholate. CONCLUSIONS: Amphotericin B desoxycholate has been implicated as
      an etiology for NDI, and the use of the newer liposomal amphotericin B reportedly
      avoids this rare complication. We observed the development of NDI despite the use
      of liposomal amphotericin B in a critically ill patient with bone marrow
      transplant.

PMID- 12503937
TI  - Flumazenil and dialysis for gabapentin-induced coma.
AB  - OBJECTIVE: To describe a case of gabapentin-induced coma that was reversed with
      flumazenil and hemodialysis. CASE SUMMARY: We describe an 83-year-old dialysis
      dependent white man who became comatose after a single dose of gabapentin for
      phantom limb pain. The patient was successfully revived from the coma with
      administration of flumazenil, which was then followed by hemodialysis. Serum
      concentration data before and 4 hours after dialysis document the effectiveness
      of hemodialysis for gabapentin toxicity. DISCUSSION: An objective causality
      assessment revealed that this adverse event was probably related to the
      gabapentin that the patient received. To our knowledge, this is the first
      documented case of not only gabapentin-induced coma, but also the effectiveness
      of flumazenil for treatment of this type of coma. Although therapeutic
      hemodialysis has been previously described, our case report is strengthened by
      the serum concentration monitoring accompanying it. CONCLUSIONS: This report
      underscores the importance of initiating gabapentin therapy at low doses in
      dialysis-dependent patients and introduces a novel treatment for those who
      experience toxicity.

PMID- 12503938
TI  - Concurrent administration of interferon alfa-2b and beta-1a.
AB  - OBJECTIVE: To describe the concurrent use of interferon (IFN) alfa and beta in a
      patient with multiple sclerosis (MS) and chronic myeloid leukemia (CML). CASE
      SUMMARY: A 60-year-old white man developed CML while receiving IFN beta-1a
      treatment for MS. The patient was started on IFN alfa-2b 1 million units 3 times
      weekly with IFN beta-1a 30 micro g weekly. The dosage of IFN alfa was increased
      to 3 million units/d 1 month later. He achieved complete hematologic remission in
      3 months. The observed adverse effects were mild and included fatigue,
      somnolence, weight loss, and difficulty with memory. At 19 months after
      treatment, the patient remained in hematologic remission and his expanded
      disability status scale score remained unchanged. DISCUSSION: Concomitant
      treatment with interferon alfa and beta by a gradual increase in the dosage of
      IFN alfa was well tolerated. Although imatinib mesylate may be a preferred
      treatment for patients with CML and MS at this time, our experience with safe
      concurrent use of IFN alfa and beta may benefit other patients who require this
      combined treatment. CONCLUSIONS: Concurrent administration of interferon alfa-2b
      and beta-1a was well tolerated by our patient with CML and MS.

PMID- 12503939
TI  - Pseudodementia associated with use of ibuprofen.
AB  - OBJECTIVE: To report a case of dementing syndrome resulting from ibuprofen use.
      CASE SUMMARY: A 76-year-old white man with normal mental status became confused,
      was lost in familiar places, and showed short-term memory loss after beginning a
      therapeutic regimen of ibuprofen 600 mg 3 times daily for osteoarthritis in
      anticipation of embarking on a foreign trip. Symptoms of dementia began within 1
      week after taking ibuprofen and resolved completely within 1 week after the
      ibuprofen regimen was stopped. This pattern was repeated 6 months later, when the
      patient again traveled abroad. Consistently before, during, and after these
      events, the patient took atenolol, clonidine, lisinopril, aspirin, vitamin C,
      lecithin, vitamin E, and multivitamins. DISCUSSION: Using the Naranjo probability
      scale, we reasoned that the patient's dementia-like syndrome could be attributed
      to the use of ibuprofen because pseudodementia appeared after the suspected drug
      was administered, improved when the drug was discontinued, reappeared when the
      drug was readministered, had no apparent alternative cause, manifested similarly
      after each exposure to ibuprofen, and was confirmed by the family's observation
      after both episodes. Objective causality assessment revealed that the adverse
      drug reaction was probable. CONCLUSIONS: Use of ibuprofen must be considered
      during clinical evaluation of any patient with new onset of dementing illness.
      The Naranjo probability scale may be clinically useful for evaluating other
      pharmaceutical agents that may be contributing to development of dementia-like
      conditions.

PMID- 12503940
TI  - Adverse reaction to a dietary supplement in an elderly patient.
AB  - OBJECTIVE: To describe the case of an elderly patient who experienced hepatic
      enzyme elevations and symptoms of hepatitis associated with the administration of
      a dietary supplement. CASE SUMMARY: A 92-year-old white woman with no history of
      hepatic disease developed jaundice and increased confusion associated with
      increased hepatic enzymes. The hepatitis panel, abdominal ultrasound, and
      antinuclear antibody screen indicated no abnormalities. A drug regimen review
      revealed that the patient was receiving a dietary supplement, Nutrilite Double X
      Multivitamin-Multimineral. Following discontinuation of the supplement, the
      patient's symptoms resolved and the hepatic enzymes decreased or returned to the
      reference range at evaluations occurring 1 week and 1 month after intervention.
      An objective causality assessment revealed this to be a probable adverse drug
      event. DISCUSSION: While the association of certain herbal preparations with
      hepatotoxicity has been demonstrated, the potential for this adverse effect is
      easily overlooked. In this patient, infectious or autoimmune causes of acute
      hepatitis were ruled out, and drug-induced causes were considered. The resolution
      of symptoms and laboratory values following discontinuation of the supplement
      support a relationship between the dietary supplement and this episode of
      hepatitis. CONCLUSIONS: Our case indicates that there was a probable relationship
      between the dietary supplement Nutrilite Double X Multivitamin-Multimineral and
      the development of acute hepatitis. Due to the multi-ingredient formulation of
      the product, as well as lack of data describing manufacturing procedures, it is
      difficult to determine which component may be associated with this effect. Over
      the-counter supplements should be considered as a part of the differential
      diagnosis in patients presenting with increased liver enzymes and related
      symptoms.

PMID- 12503941
TI  - Dispensing error leading to alendronate ingestion.
AB  - OBJECTIVE: To report a case of medication dispensing error by administration of
      similarly packaged drugs. CASE SUMMARY: A 6-year-old East Indian boy with asthma
      was mistakenly given alendronate, a bisphosphonate, for 3 months instead of
      montelukast, a leukotriene-receptor antagonist. Symptoms of esophageal irritation
      developed and disappeared on discontinuation of alendronate. DISCUSSION:
      Alendronate and montelukast have very similar packaging and are available in
      dosages that also can be similar for some patients. Alendronate caused symptoms
      of irritative gastritis in this child before the error was identified. This case
      report emphasizes one of the possible sources of medication dispensing errors: a
      mistaken identification due to similar packaging (confirmation bias).
      Manufacturers can help to prevent medication errors in many ways; in this case,
      more distinct packaging would have decreased the risk of error. A standard bar
      coding scheme among manufacturers could lead to an important improvement in the
      safety of medication dispensation. Practitioners are also encouraged to report
      such errors to the United States Pharmacopoeia Medication Errors Reporting
      Program. CONCLUSIONS: With increased awareness of medication errors, healthcare
      practitioners, manufacturers, and patients should take precautionary steps to
      prevent dispensing errors and their consequences.

PMID- 12503942
TI  - Caspofungin acetate for treatment of invasive fungal infections.
AB  - OBJECTIVE: To briefly discuss the changing epidemiology of fungal infections and
      review currently available agents; provide a review of caspofungin; and discuss
      its pharmacology, pharmacokinetics, dosing guidelines, safety and efficacy, and
      role in the treatment of invasive fungal infections as it relates to current
      antifungal therapy. DATA SOURCES: A MEDLINE (1966 to August 2002) database search
      using key words caspofungin, echino candins, fungal infections, and invasive
      aspergillosis, was completed to identify relevant articles including reviews,
      recent studies, treatment guidelines, and data from Merck and Company. STUDY
      SELECTION: In vitro studies and all clinical trials were evaluated to summarize
      the clinical efficacy and safety of caspofungin. DATA SYNTHESIS: The incidence of
      fungal infections is increasing as the population at risk expands. Cost,
      resistance, and morbidity and mortality are key issues. Adding to the antifungal
      armamentarium is necessary to address these therapeutic dilemmas. Caspofungin is
      the first member of a new class of antifungal agents, the echinocandins, to be
      approved for clinical use. Caspofungin is classified as a glucan synthase
      inhibitor and represents a class of agents with a novel mechanism of action.
      Unlike currently available agents (polyenes, pyrimidines, azoles) that exert
      their effect on the fungal cell membrane, the echinocandins are the first agents
      to inhibit fungal cell wall synthesis. Caspofungin exhibits activity against
      Aspergillus spp. and Candida spp., including non-albicans species. Data from
      clinical trials demonstrate that caspofungin is effective in patients with
      invasive aspergillosis as well as candida esophagitis. Its Food and Drug
      Administration-approved indication is limited to invasive aspergillosis
      refractory to or intolerant of current therapy. CONCLUSIONS: Caspofungin has
      activity against Aspergillus spp. as well as a variety of Candida spp. Clinical
      data support its usefulness in the treatment of invasive aspergillosis and select
      candida infections. As additional clinical data become available, it seems likely
      that the therapeutic role of caspofungin will expand.

PMID- 12503943
TI  - Olmesartan medoxomil: the seventh angiotensin receptor antagonist.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse
      effects of olmesartan medoxomil, an angiotensin II receptor antagonist for the
      treatment of hypertension. DATA SOURCES: Information was obtained from MEDLINE
      searches (1996-April 2002) of English-language medical literature. Search terms
      included CS-866, olmesartan, olmesartan medoxomil, RNH-6270 (active metabolite of
      olmesartan), Benicar, angiotensin receptors, and antihypertensive agents. In
      addition, references from relevant articles were reviewed for additional
      citations. The authors independently reviewed literature identified in the
      searches. Studies evaluating olmesartan (i.e., abstracts, clinical trials, data
      on file with manufacturer) were considered for inclusion. STUDY SELECTION: All
      articles identified from data sources with pertinent information regarding
      olmesartan medoxomil were evaluated, and all information deemed relevant was
      included in this review. DATA SYNTHESIS: Olmesartan medoxomil is a competitively
      priced addition to the class of angiotensin II receptor antagonists. Monotherapy
      with olmesartan medoxomil in once-daily doses of 20-40 mg has produced
      significant reductions in systolic and diastolic blood pressure in hypertensive
      patients. Adverse effects have been minimal with olmesartan medoxomil, with
      dizziness being the only adverse effect occurring more often than with placebo in
      clinical trials. Additionally, animal studies indicate that olmesartan medoxomil
      may prove to be useful treatment for diabetic nephropathy, as well as
      atherosclerosis. CONCLUSIONS: Olmesartan medoxomil has a favorable safety and
      efficacy profile, with blood pressure-lowering effects comparable to those of
      other angiotensin receptor blockers (i.e., losartan, valsartan, irbesartan). At
      this time, formulary decisions will be driven primarily by economic issues.
      Theoretical benefits of olmesartan medoxomil in reducing atherogenesis and
      lowering angiotensin II concentrations better than the alternative agents will be
      determined only with more extensive research.

PMID- 12503944
TI  - Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed
      dyslipidemia.
AB  - OBJECTIVE: To review the currently available information on the once-daily
      combination of niacin extended-release (ER)/lovastatin in the treatment of
      patients with hypercholesterolemia and mixed dyslipidemia at high risk for
      cardiovascular events. DATA SOURCES: MEDLINE (1966-July 2002) was searched for
      primary and review articles. Data from the manufacturer were also included. STUDY
      SELECTION/DATA EXTRACTION: All articles and product labeling deemed relevant to
      the combination of niacin and statins (i.e., lovastatin) were included for
      review. English-language studies selected for inclusion were limited to those
      with human subjects. DATA SYNTHESIS: The Food and Drug Administration approved a
      new fixed-dose combination of niacin-ER/lovastatin, which is administered once
      daily. The efficacy and safety of the combined agent have been proven to be
      similar to either component used alone or in combination for management of
      hyperlipidemia and mixed dyslipidemia. CONCLUSIONS: Elevated low-density
      lipoprotein cholesterol (LDL-C) is independently associated with a higher risk
      for cardiovascular events. Lowering of elevated LDL-C concentrations with statin
      monotherapy may be insufficient in patients at high risk for cardiovascular
      events. In fact, consideration of elevated triglycerides (TGs) and/or low
      concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with
      elevated LDL-C places them at greater risk. The addition of niacin may enhance or
      improve the lipid profile of those who require a further decrease of TGs and/or
      increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy
      similar to that of immediate-release niacin, but minimal myopathy and
      hepatotoxicity (compared with sustained-release niacin). Although no clinical
      outcomes are available, current evidence shows that the combination product
      offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest
      that therapy with the niacin-ER and lovastatin combination product is safe and
      does not increase the incidence of adverse effects.

PMID- 12503945
TI  - Aspirin dose for prevention of cardiovascular disease in diabetics.
AB  - OBJECTIVE: To determine whether a specific dose of aspirin can be recommended for
      prevention of cardiovascular disease in patients with diabetes. DATA SOURCE:
      Biomedical literature was accessed through MEDLINE (1990-February 2002). Key
      terms included diabetes, cardiovascular protection, and aspirin. DATA SYNTHESIS:
      Pharmacologic and clinical studies focusing on the dose-response relationship of
      aspirin therapy were reviewed. Evidence supports the benefit of low-dose aspirin
      therapy in reducing vascular events in secondary and primary prevention trials in
      various patient populations; however, some studies suggest larger doses of
      aspirin may be needed in certain patients. CONCLUSIONS: Review of the evidence
      does not support a particular dose of aspirin for cardiovascular protection in
      diabetic patients. Clinical guidelines recommend aspirin therapy in the range of
      81-325 mg/d. However, due to an increased prevalence of cardiovascular morbidity
      and disturbances in coagulation in diabetic patients, the dose of aspirin for
      prevention of cardiovascular disease in these individuals may be different from
      that in other populations and requires further evaluation.

PMID- 12503946
TI  - Chronic metoclopramide therapy for diabetic gastroparesis.
AB  - OBJECTIVE: To review the safety and efficacy of chronic metoclopramide for
      diabetic gastroparesis. DATA SOURCES: Medical literature was accessed through
      MEDLINE (1965 to October 2002) and PubMed (1965 to October 2002). Key search
      terms included metoclopramide; diabetic gastroparesis; and dyskinesia, drug
      induced. DATA SYNTHESIS: Metoclopramide is often used for diabetic gastroparesis,
      despite the risk of tardive dyskinesia. Published information is limited
      regarding long-term efficacy and toxicity of metoclopramide. The literature was
      assessed concerning these topics. CONCLUSIONS: Limited data do not provide
      sufficient evidence to conclude whether metoclopramide is efficacious for chronic
      use. Routine monitoring may mitigate the risk associated with metoclopramide
      therapy.

PMID- 12503947
TI  - Management of botulism.
AB  - OBJECTIVE: To provide a concise review of the presentation and treatment of
      botulism. DATA SOURCES: Searches of MEDLINE (1966-November 2001), tertiary
      references, and public and government Internet sites were conducted. STUDY
      SELECTION: All articles and additional references from those articles were
      thoroughly evaluated. DATA SYNTHESIS: Clostridium botulinum toxin blocks
      acetylcholine release in a dose-dependent fashion, resulting in acute symmetric
      diplopia, dysarthria, dysphonia, dysphagia, and possible neurologic sequelae
      despite the route of exposure (i.e., food-borne, wound, intestinal, inhalation).
      Disease secondary to genetically engineered C. botulinum may differ from that of
      inadvertent exposure. Present treatment is primarily supportive care, respiratory
      support, rapid decontamination, and antitoxin administration (i.e., trivalent,
      pentavalent, heptavalent antitoxin). Early initiation of antitoxin limits the
      extent of paralysis, but does not reverse it. CONCLUSIONS: Supportive care and
      the use of antitoxin have been effective in the treatment of botulism from food
      borne, intestinal, and wound exposure. However, the effectiveness of antitoxin in
      the treatment of inhaled C. botulinum has not been proven.

PMID- 12503948
TI  - Bioterrorism web sites for pharmacists.
AB  - OBJECTIVE: To identify Internet Web sites for ease of accessibility to
      bioterrorism-related information, comprehensive provision of bioterrorism-related
      information, and provision of bioterrorism information that specifically pertains
      to the pharmacy profession. DATA SOURCES: Web sites of national pharmacy
      organizations, US government agencies, and medical organizations, as well as Web
      sites related to bioterrorism. DATA SYNTHESIS: Pharmacists need access to
      relevant bioterrorism information in a timely manner. An evaluation of Web sites
      was performed to identify those that include a discussion of the potential
      infectious microorganisms and prevention and treatment methods, as well as unique
      features for pharmacy practice. RESULTS: The American Society of Health-System
      Pharmacists and American Pharmaceutical Association Web sites provide pharmacy
      specific recommendations. The Centers for Disease Control and Prevention provides
      biological agent information and health department contact numbers. Additional
      agent-specific data are provided by the American Medical Association, The Johns
      Hopkins University, and the Food and Drug Administration (FDA) Web sites.
      Information addressing food safety is provided by the FDA. CONCLUSIONS: Pharmacy
      specific bioterrorism information is available only at selected national pharmacy
      organization Internet Web sites. However, other Web sites provide comprehensive
      bioterrorism information useful for pharmacists.

PMID- 12503949
TI  - Why aren't lower, effective, OTC doses available earlier by prescription?
AB  - BACKGROUND: Many popular oral over-the-counter (OTC) drugs were originally
      available only by prescription, but not at the low doses contained in their OTC
      counterparts. Yet, if OTC doses are effective for treating mild symptoms, why
      weren't these low, often safer doses made available at least by prescription when
      the drugs were first approved? OBJECTIVE: To examine issues surrounding the
      delayed approval of OTC doses by the Food and Drug Administration (FDA). METHODS:
      Information reviewed included package inserts, data obtained from manufacturers,
      and articles published in MEDLINE (1966 to December 2001). Medications examined
      included presently available and potentially approved OTC antiinflammatory,
      gastrointestinal, and antihistamine drugs. RESULTS: Considerable data demonstrate
      the effectiveness of ibuprofen, naproxen, ranitidine, famotidine, nizatidine,
      diphenhydramine, and clemastine at OTC doses. Published studies also show the
      effectiveness of celecoxib, omeprazole, and fexofenadine at doses 33-50% lower
      than currently recommended for prescription use. CONCLUSIONS: OTC doses are
      effective for many patients with mild symptoms and for some with serious
      symptoms. However, OTC-like doses are usually not offered when drugs are approved
      for prescription use because new drugs are usually studied in patients with
      serious conditions requiring higher doses; manufacturers and the FDA seem to
      prefer a middle-dose approach; >75% of subjects in premarketing dose studies are
      male; and averaging the responses of study subjects may obscure a wide range of
      interindividual variation in drug response. Simplistic dosage guidelines make
      therapeutic decisions easier. Because dose-related adverse effects frequently
      diminish quality-of-life and reduce adherence, the early availability of OTC-like
      doses, at least by prescription, would allow healthcare professionals greater
      flexibility in matching medication doses to patients' widely differing needs.

PMID- 12503950
TI  - Oral antithrombotic use among myocardial infarction patients.
AB  - OBJECTIVE: To examine the use of oral antithrombotics (i.e., antiplatelet agents,
      oral anticoagulants) after myocardial infarction (MI) in the Netherlands from
      1988 to 1998. METHODS: Retrospective follow-up of 3800 patients with MI, using
      data from the PHARMO Record Linkage System. RESULTS: From 1988 to 1998, oral
      antithrombotic treatment increased significantly from 54.0% to 88.9%. In 1998,
      only 75.8% of patients who experienced a MI in the late 1980s received oral
      antithrombotic treatment compared with 94.4% of those who experienced a recent
      MI. CONCLUSIONS: Oral antithrombotics were considerably underused in patients
      with a past history of MI. Therefore, these patients should be reviewed for
      antithrombotic therapy to assess whether their failure to use oral
      antithrombotics was right or wrong, and whether treatment should be initiated if
      possible.

PMID- 12503951
TI  - Pancytopenia associated with leflunomide and methotrexate.

PMID- 12503952
TI  - Olanzapine-associated seizure.

PMID- 12503953
TI  - Suspected withdrawal syndrome after cessation of St. John's wort.

PMID- 12503954
TI  - Dissolution test for liquid formulations of omeprazole enteric-coated products.

PMID- 12503955
TI  - A piece of my mind. Will the real doctor please stand up?

PMID- 12503956
TI  - Growing, evolving HIV/AIDS pandemic is producing social and economic fallout.

PMID- 12503957
TI  - Economist takes aim at "big fat" US lifestyle.

PMID- 12503964
TI  - Corticosteroids for patients with septic shock.

PMID- 12503965
TI  - Corticosteroids for patients with septic shock.

PMID- 12503966
TI  - Corticosteroids for patients with septic shock.

PMID- 12503967
TI  - Corticosteroids for patients with septic shock.

PMID- 12503968
TI  - Corticosteroids for patients with septic shock.

PMID- 12503969
TI  - Corticosteroids for patients with septic shock.

PMID- 12503970
TI  - Corticosteroids for patients with septic shock.

PMID- 12503971
TI  - Relationship between hormone replacement therapy, socioeconomic status, and
      coronary heart disease.

PMID- 12503973
TI  - Direct-to-consumer advertising of genetic testing.

PMID- 12503975
TI  - Mode of delivery and risk of postpartum rehospitalization.

PMID- 12503976
TI  - Prevalence of autism in a US metropolitan area.
AB  - CONTEXT: Concern has been raised about possible increases in the prevalence of
      autism. However, few population-based studies have been conducted in the United
      States. OBJECTIVES: To determine the prevalence of autism among children in a
      major US metropolitan area and to describe characteristics of the study
      population. DESIGN, SETTING, AND POPULATION: Study of the prevalence of autism
      among children aged 3 to 10 years in the 5 counties of metropolitan Atlanta, Ga,
      in 1996. Cases were identified through screening and abstracting records at
      multiple medical and educational sources, with case status determined by expert
      review. MAIN OUTCOME MEASURES: Autism prevalence by demographic factors, levels
      of cognitive functioning, previous autism diagnoses, special education
      eligibility categories, and sources of identification. RESULTS: A total of 987
      children displayed behaviors consistent with Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition criteria for autistic disorder, pervasive
      developmental disorder-not otherwise specified, or Asperger disorder. The
      prevalence for autism was 3.4 per 1000 (95% confidence interval [CI], 3.2-3.6)
      (male-female ratio, 4:1). Overall, the prevalence was comparable for black and
      white children (black, 3.4 per 1000 [95% CI, 3.0-3.7] and white, 3.4 per 1000
      [95% CI, 3.2-3.7]). Sixty-eight percent of children with IQ or developmental test
      results (N = 880) had cognitive impairment. As severity of cognitive impairment
      increased from mild to profound, the male-female ratio decreased from 4.4 to 1.3.
      Forty percent of children with autism were identified only at educational
      sources. Schools were the most important source for information on black
      children, children of younger mothers, and children of mothers with less than 12
      years of education. CONCLUSION: The rate of autism found in this study was higher
      than the rates from studies conducted in the United States during the 1980s and
      early 1990s, but it was consistent with those of more recent studies.

PMID- 12503977
TI  - Treatment of antidepressant-associated sexual dysfunction with sildenafil: a
      randomized controlled trial.
AB  - CONTEXT: Sexual dysfunction is a common adverse effect of antidepressants that
      frequently results in treatment noncompliance. OBJECTIVE: To assess the efficacy
      of sildenafil citrate in men with sexual dysfunction associated with the use of
      selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants.
      DESIGN, SETTING, AND PATIENTS: Prospective, parallel-group, randomized, double
      blind, placebo-controlled trial conducted between November 1, 2000, and January
      1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD]
      age, 45 [8] years) with major depression in remission and sexual dysfunction
      associated with SRI antidepressant treatment. INTERVENTION: Patients were
      randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible
      dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6
      weeks. MAIN OUTCOME MEASURES: The primary outcome measure was score on the
      Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were
      scores on the International Index of Erectile Function, Arizona Sexual Experience
      Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and
      Hamilton Rating Scale for Depression (HAM-D). RESULTS: Among the 90 randomized
      patients, 93% (83/89) of patients treated per protocol took at least 1 dose of
      study drug and 85% (76/89) completed week 6 end-point assessments with last
      observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5%
      (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or
      very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and
      overall satisfaction domain measures improved significantly in sildenafil
      compared with placebo patients. Mean depression scores remained consistent with
      remission (HAM-D score < or =10) in both groups for the study duration.
      CONCLUSION: In our study, sildenafil effectively improved erectile function and
      other aspects of sexual function in men with sexual dysfunction associated with
      the use of SRI antidepressants. These improvements may allow patients to maintain
      adherence with effective antidepressant treatment.

PMID- 12503978
TI  - Prophylactic treatment of migraine with an angiotensin II receptor blocker: a
      randomized controlled trial.
AB  - CONTEXT: There is a paucity of effective, well-tolerated drugs available for
      migraine prophylaxis. OBJECTIVE: To determine whether treatment with the
      angiotensin II receptor blocker candesartan is effective as a migraine
      prophylactic drug. DESIGN AND SETTING: Randomized, double-blind, placebo
      controlled crossover study performed in a Norwegian neurological outpatient
      clinic from January 2001 to February 2002. PATIENTS: Sixty patients aged 18 to 65
      years with 2 to 6 migraine attacks per month were recruited mainly from newspaper
      advertisements. INTERVENTIONS: A placebo run-in period of 4 weeks was followed by
      two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty
      patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet
      daily in the first treatment period followed by 1 placebo tablet daily in the
      second period. The remaining 30 received placebo followed by candesartan. MAIN
      OUTCOME MEASURES: The primary end point was number of days with headache;
      secondary end points included hours with headache, days with migraine, hours with
      migraine, headache severity index, level of disability, doses of triptans, doses
      of analgesics, acceptability of treatment, days of sick leave, and quality-of
      life variables on the Short Form 36 questionnaire. RESULTS: In a period of 12
      weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with
      candesartan (P =.001) in the intention-to-treat analysis (n = 57). Some secondary
      end points also favored candesartan, including hours with headache (139 vs 95;
      P<.001), days with migraine (12.6 vs 9.0; P<.001), hours with migraine (92.2 vs
      59.4; P<.001), headache severity index (293 vs 191; P<.001), level of disability
      (20.6 vs 14.1; P<.001) and days of sick leave (3.9 vs 1.4; P =.01), although
      there were no significant differences in health-related quality of life. The
      number of candesartan responders (reduction of > or =50% compared with placebo)
      was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with
      migraine. Adverse events were similar in the 2 periods. CONCLUSION: In this
      study, the angiotensin II receptor blocker candesartan provided effective
      migraine prophylaxis, with a tolerability profile comparable with that of
      placebo.

PMID- 12503979
TI  - Binge drinking among US adults.
AB  - CONTEXT: Binge drinking (consuming > or =5 alcoholic drinks on 1 occasion)
      generally results in acute impairment and has numerous adverse health
      consequences. Reports indicate that binge drinking may be increasing in the
      United States. OBJECTIVES: To quantify episodes of binge drinking among US adults
      in 1993-2001, to characterize adults who engage in binge drinking, and to
      describe state and regional differences in binge drinking. DESIGN, SETTING, AND
      PARTICIPANTS: The Behavioral Risk Factor Surveillance System, a random-digit
      telephone survey of adults aged 18 years or older that is conducted annually in
      all states. The sample size ranged from 102 263 in 1993 to 212 510 in 2001. MAIN
      OUTCOME MEASURES: Binge-drinking prevalence, episodes, and episodes per person
      per year. RESULTS: Between 1993 and 2001, the total number of binge-drinking
      episodes among US adults increased from approximately 1.2 billion to 1.5 billion;
      during this time, binge-drinking episodes per person per year increased by 17%
      (from 6.3 to 7.4, P for trend =.03). Between 1995 and 2001, binge-drinking
      episodes per person per year increased by 35% (P for trend =.005). Men accounted
      for 81% of binge-drinking episodes in the study years. Although rates of binge
      drinking episodes were highest among those aged 18 to 25 years, 69% of binge
      drinking episodes during the study period occurred among those aged 26 years or
      older. Overall, 47% of binge-drinking episodes occurred among otherwise moderate
      (ie, non-heavy) drinkers, and 73% of all binge drinkers were moderate drinkers.
      Binge drinkers were 14 times more likely to drive while impaired by alcohol
      compared with non-binge drinkers. There were substantial state and regional
      differences in per capita binge-drinking episodes. CONCLUSIONS: Binge drinking is
      common among most strata of US adults, including among those aged 26 years or
      older. Per capita binge-drinking episodes have increased, particularly since
      1995. Binge drinking is strongly associated with alcohol-impaired driving.
      Effective interventions to prevent the mortality and morbidity associated with
      binge drinking should be widely adopted, including screening patients for alcohol
      abuse in accordance with national guidelines.

PMID- 12503980
TI  - Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001.
AB  - CONTEXT: Obesity and diabetes are increasing in the United States. OBJECTIVE: To
      estimate the prevalence of obesity and diabetes among US adults in 2001. DESIGN,
      SETTING, AND PARTICIPANTS: Random-digit telephone survey of 195 005 adults aged
      18 years or older residing in all states participating in the Behavioral Risk
      Factor Surveillance System in 2001. MAIN OUTCOME MEASURES: Body mass index, based
      on self-reported weight and height and self-reported diabetes. RESULTS: In 2001
      the prevalence of obesity (BMI > or =30) was 20.9% vs 19.8% in 2000, an increase
      of 5.6%. The prevalence of diabetes increased to 7.9% vs 7.3% in 2000, an
      increase of 8.2%. The prevalence of BMI of 40 or higher in 2001 was 2.3%.
      Overweight and obesity were significantly associated with diabetes, high blood
      pressure, high cholesterol, asthma, arthritis, and poor health status. Compared
      with adults with normal weight, adults with a BMI of 40 or higher had an odds
      ratio (OR) of 7.37 (95% confidence interval [CI], 6.39-8.50) for diagnosed
      diabetes, 6.38 (95% CI, 5.67-7.17) for high blood pressure, 1.88 (95% CI,1.67
      2.13) for high cholesterol levels, 2.72 (95% CI, 2.38-3.12) for asthma, 4.41 (95%
      CI, 3.91-4.97) for arthritis, and 4.19 (95% CI, 3.68-4.76) for fair or poor
      health. CONCLUSIONS: Increases in obesity and diabetes among US adults continue
      in both sexes, all ages, all races, all educational levels, and all smoking
      levels. Obesity is strongly associated with several major health risk factors.

PMID- 12503981
TI  - Does this patient have acute cholecystitis?
AB  - CONTEXT: Although few patients with acute abdominal pain will prove to have
      cholecystitis, ruling in or ruling out acute cholecystitis consumes substantial
      diagnostic resources. OBJECTIVE: To determine if aspects of the history and
      physical examination or basic laboratory testing clearly identify patients who
      require diagnostic imaging tests to rule in or rule out the diagnosis of acute
      cholecystitis. DATA SOURCES: Electronic search of the Science Citation Index,
      Cochrane Library, and English-language articles from January 1966 through
      November 2000 indexed in MEDLINE. We also hand-searched Index Medicus for 1950
      1965, and scanned references in identified articles and bibliographies of
      prominent textbooks of physical examination, surgery, and gastroenterology. To
      identify relevant articles appearing since the comprehensive search, we repeated
      the MEDLINE search in July 2002. STUDY SELECTION: Included studies evaluated the
      role of the history, physical examination, and/or laboratory tests in adults with
      abdominal pain or suspected acute cholecystitis. Studies had to report data from
      a control group found not to have acute cholecystitis. Acceptable definitions of
      cholecystitis included surgery, pathologic examination, hepatic iminodiacetic
      acid scan or right upper quadrant ultrasound, or clinical course consistent with
      acute cholecystitis and no evidence for an alternate diagnosis. Studies of
      acalculous cholecystitis were included. Seventeen of 195 identified studies met
      the inclusion criteria. DATA EXTRACTION: Two authors independently abstracted
      data from the 17 included studies. Disagreements were resolved by discussion and
      consensus with a third author. DATA SYNTHESIS: No clinical or laboratory finding
      had a sufficiently high positive likelihood ratio (LR) or low negative LR to rule
      in or rule out the diagnosis of acute cholecystitis. Possible exceptions were the
      Murphy sign (positive LR, 2.8; 95% CI, 0.8-8.6) and right upper quadrant
      tenderness (negative LR, 0.4; 95% CI, 0.2-1.1), though the 95% CIs for both
      included 1.0. Available data on diagnostic confirmation rates at laparotomy and
      test characteristics of relevant radiological investigations suggest that the
      diagnostic impression of acute cholecystitis has a positive LR of 25 to 30.
      Unfortunately, the available literature does not identify the specific
      combinations of clinical and laboratory findings that presumably account for this
      diagnostic success. CONCLUSIONS: No single clinical finding or laboratory test
      carries sufficient weight to establish or exclude cholecystitis without further
      testing (eg, right upper quadrant ultrasound). Combinations of certain symptoms,
      signs, and laboratory results likely have more useful LRs, and presumably inform
      the diagnostic impressions of experienced clinicians. Pending further research
      characterizing the pretest probabilities associated with different clinical
      presentations, the evaluation of patients with abdominal pain suggestive of
      cholecystitis will continue to rely heavily on the clinical gestalt and
      diagnostic imaging.

PMID- 12503982
TI  - The prevalence of autism.

PMID- 12503983
TI  - Improving reports of studies of diagnostic tests: the STARD initiative.

PMID- 12503985
TI  - MSJAMA. Patient-physician communication.

PMID- 12503986
TI  - MSJAMA. Communication skills education in medical school and beyond.

PMID- 12503987
TI  - MSJAMA. Cultural diversity: an evolving challenge to physician-patient
      communication.

PMID- 12503988
TI  - MSJAMA. Risk communication: problems of presentation and understanding.

PMID- 12503989
TI  - MSJAMA. Advance directives and patient-physician communication.

PMID- 12503995
TI  - JAMA patient page. Acute cholecystitis.

PMID- 12503996
TI  - Effect of Kohl-Chikni Dawa - a compound ophthalmic formulation of Unani medicine
      on naphthalene-induced cataracts in rats.
AB  - BACKGROUND: Cataracts are the leading cause of blindness worldwide, accounting
      for 13-27% of cases. Kohl-Chikni Dawa (KCD) is reputed for its beneficial effects
      in the treatment of premature cataracts. However, its efficacy is yet to be
      tested. To investigate the rationality of the therapeutic use of Kohl-Chikni Dawa
      (KCD) in Unani medicine. METHODS: The effect of Kohl-Chikni Dawa eye drops on
      naphthalene-induced cataracts in rats was investigated by slit-lamp
      biomicroscopic analysis. The normal group of experimental animals was
      administered with mineral oil (orally), while other groups were given naphthalene
      (orally) along with local application of KCD eye drops (once and twice daily),
      placebo and distilled water (twice daily). Initial morphological changes of the
      lenses were observed twice a week for two weeks, and thereafter once a week for
      four weeks. RESULTS: Local application of KCD (twice daily) caused significant
      reduction in the lens opacification after 2 to 4 weeks of naphthalene
      administration. CONCLUSION: KCD eye drops may have the potential to delay
      progression of naphthalene-induced cataracts in rats.

PMID- 12503997
TI  - Aha, another regulator for hsp90 chaperones.
AB  - A large number of key regulators controlling homeostasis and cell fate are
      chaperoned by the Hsp90 folding machine. In this issue of Molecular Cell, report
      the discovery of a new stress-regulated cochaperone, Aha1, which accelerates the
      dynamics of this machine.

PMID- 12503998
TI  - Hitchhikers guide to the vacuole-mechanisms of cargo sequestration in the Cvt and
      autophagic pathways.
AB  - In the yeast Saccharomyces cerevisiae, precursor aminopeptidase I and alpha
      mannosidase are selectively targeted via the Cvt and the autophagic pathways to
      the vacuole. Two studies now uncover the molecular basis of the selective
      sequestration of these two enzymes.

PMID- 12503999
TI  - Signaling from the far side.
AB  - Signaling by cell surface receptors is often turned off by receptor endocytosis
      and downregulation. However, it appears that some signaling pathways continue to
      fire from within cells. A recent study now suggests that a late endosomal p14/MP1
      MAPK scaffold complex is critical for the ERK signaling pathway.

PMID- 12504000
TI  - Inflating cell numbers by Wnt.
AB  - One of the prominent biological phenomena controlled by Wnt signaling is the
      expansion of cells with predefined fates. In the November 27, 2002, issue of
      Cell, Rosenfeld and colleagues describe an example of Wnt-controlled
      proliferation during genesis of the cardiac outflow tract and the pituitary
      gland. As a downstream target gene of the Wnt cascade, the bicoid-related
      transcription factor Pitx2 directly drives proliferation in these tissues.

PMID- 12504001
TI  - BRCA2 keeps Rad51 in line. High-fidelity homologous recombination prevents breast
      and ovarian cancer?
AB  - The mechanistic link between the BRCA2 protein, homologous recombination, and
      genomic instability has become clearer as a result of recent work describing the
      structures of different BRCA2 domains bound to Rad51 and to single-stranded DNA.

PMID- 12504002
TI  - The transcription cycle in vivo. A blind watchmaker at work.
AB  - Recent work by the Cook and Misteli laboratories addresses the issue of assembly
      and action of the transcription machinery. Live cell studies of RNA polymerases I
      (RNAP1) and II (RNAP2) indicate that transcription complexes are assembled in a
      stochastic fashion from freely diffusible subunits. This contrasts to models
      involving stable holo-complexes.

PMID- 12504003
TI  - Take your vitamins with a pinch of RNA.
AB  - RNA "aptamers" capable of binding and discriminating among structurally related
      small molecules can be concocted in the laboratory. Two groups have now
      discovered that conserved domains in the 5' ends of some mRNAs bind specific
      metabolites and respond by changing their shape in biologically useful ways,
      demonstrating that aptamers also are present in the natural world.

PMID- 12504004
TI  - Mechanism of recruitment of WASP to the immunological synapse and of its
      activation following TCR ligation.
AB  - F-actin polymerization following engagement of the T cell receptor (TCR) is
      dependent on WASP and is critical for T cell activation. The link between TCR and
      WASP is not fully understood. In resting cells, WASP exists in a complex with
      WIP, which inhibits its activation by Cdc42. We show that the adaptor protein
      CrkL binds directly to WIP. Further, TCR ligation results in the formation of a
      ZAP-70-CrkL-WIP-WASP complex, which is recruited to lipid rafts and the
      immunological synapse. TCR engagement also causes PKCtheta-dependent
      phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP
      complex, thereby releasing it from WIP inhibition. These results suggest that the
      ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation.

PMID- 12504005
TI  - B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction
      of Rel/NF-kappaB regulated c-myc transcription.
AB  - Rel/NF-kappaB transcription factors regulate the division and survival of B
      lymphocytes. Here we show that B cells lacking NF-kappaB1 and c-Rel fail to
      increase in size upon mitogenic stimulation due to a reduction in induced c-myc
      expression. Mitogen-induced B cell growth, although not markedly impaired by
      FRAP/mTOR or MEK inhibitors, required phosphatidylinositol 3-kinase (PI3K)
      activity. Inhibition of PI3K-dependent growth coincided with a block in the
      nuclear import of NF-kappaB1/c-Rel dimers and a failure to upregulate c-myc. In
      addition, PI3K was shown to be necessary for a transcription-independent increase
      in c-Myc protein levels that accompanies mitogenic activation. Collectively,
      these findings establish a role for Rel/NF-kappaB signaling in the mitogen
      induced growth of mammalian cells, which in B lymphocytes requires a PI3K/c-myc
      dependent pathway.

PMID- 12504006
TI  - Regulation of subtelomeric silencing during stress response.
AB  - Sir proteins play a critical role in silent chromatin domains. While mutations
      can cause derepression of heterochromatin, it remains unclear whether silencing
      is actively involved in transcriptional control under changing environmental
      conditions. We find that TOR inhibits Sir3 phosphorylation. Rapamycin or stress
      induced by chlorpromazine leads to activation of MAP kinase Mpk1/Slt2, which
      phosphorylates Sir3. Sir3 hyperphosphorylation is correlated with reduced
      subtelomeric silencing, increased subtelomeric cell wall gene expression, and
      stress resistance to chlorpromazine, but does not affect the silent HML and rDNA
      loci. Based on these observations, we propose that regulation of silencing may be
      used to control gene expression at specific silent chromatin domains in response
      to stress and possibly other environmental changes.

PMID- 12504007
TI  - Activation of the ATPase activity of hsp90 by the stress-regulated cochaperone
      aha1.
AB  - Client protein activation by Hsp90 involves a plethora of cochaperones whose
      roles are poorly defined. A ubiquitous family of stress-regulated proteins have
      been identified (Aha1, activator of Hsp90 ATPase) that bind directly to Hsp90 and
      are required for the in vivo Hsp90-dependent activation of clients such as v-Src,
      implicating them as cochaperones of the Hsp90 system. In vitro, Aha1 and its
      shorter homolog, Hch1, stimulate the inherent ATPase activity of yeast and human
      Hsp90. The identification of these Hsp90 cochaperone activators adds to the
      complex roles of cochaperones in regulating the ATPase-coupled conformational
      changes of the Hsp90 chaperone cycle.

PMID- 12504008
TI  - Asymmetric sorting of ash1p in yeast results from inhibition of translation by
      localization elements in the mRNA.
AB  - ASH1 mRNA localizes at the bud tip of late-anaphase yeast, resulting in
      accumulation of Ash1p in the daughter nucleus. We show that disruption of the
      secondary structure, but not the protein coding, of all four ASH1 localization
      elements resulted in RNA and protein delocalization. Localization of both was
      incrementally restored by replacement of each of the four elements. However,
      transposition of the elements to the 3'UTR reinstated the RNA, but not the
      protein, localization. Interestingly, the mutant ASH1 mRNA was translated more
      efficiently, suggesting that asymmetry of Ash1p resulted from translational
      inhibition by the localization elements. In support of this, Ash1p asymmetry
      could be rescued by slowing its translation.

PMID- 12504009
TI  - Nuclear export of NF90 is required for interleukin-2 mRNA stabilization.
AB  - In response to T cell activation signals, the half-life of interleukin-2 (IL-2)
      mRNA is greatly extended. The cis elements mediating IL-2 mRNA stabilization are
      located in its 5' and 3' untranslated regions (UTR). The 3'UTR also contains AU
      rich elements (AREs) that mediate rapid IL-2 mRNA degradation in the cytoplasm of
      nonstimulated T cells. NF90, a previously described RNA binding protein, binds to
      a subregion of the 3'UTR that contains several AREs and slows down the
      degradation of IL-2 mRNA. In nonstimulated cells, NF90 is mostly nuclear, but T
      cell activation results in its accumulation in the cytoplasm. The nuclear export
      of NF90 is required for IL-2 mRNA stabilization.

PMID- 12504010
TI  - Molecular basis for the recognition of a nonclassical nuclear localization signal
      by importin beta.
AB  - Nuclear import of proteins containing a classical nuclear localization signal
      (NLS) involves NLS recognition by importin alpha, which associates with importin
      beta via the IBB domain. Other proteins, including parathyroid hormone-related
      protein (PTHrP), are imported into the nucleus by direct interaction with
      importin beta. We solved the crystal structure of a fragment of importin beta-1
      (1-485) bound to the nonclassical NLS of PTHrP. The structure reveals a second
      extended cargo binding site on importin beta distinct from the IBB domain binding
      site. Using a permeabilized cell import assay we demonstrate that importin beta
      (1-485) can import PTHrP-coupled cargo in a Ran-dependent manner. We propose that
      this region contains a prototypical nuclear import receptor domain, which could
      have evolved into the modern importin beta superfamily.

PMID- 12504011
TI  - DNA polymerase clamp shows little turnover at established replication sites but
      sequential de novo assembly at adjacent origin clusters.
AB  - The spatial and temporal organization of DNA replication was investigated in
      living cells with a green fluorescent protein fusion to the DNA polymerase clamp
      PCNA. In situ extractions and photobleaching experiments revealed that PCNA,
      unlike RPA34, shows little if any turnover at replication sites, suggesting that
      it remains associated with the replication machinery through multiple rounds of
      Okazaki fragment synthesis. Photobleaching analyses further showed that the
      transition from earlier to later replicons occurs by disassembly into a
      nucleoplasmic pool of rapidly diffusing subcomponents and reassembly at newly
      activated sites. The fact that these replication sites were de novo assembled in
      close proximity to earlier ones suggests that activation of neighboring origins
      may occur by a domino effect possibly involving local changes in chromatin
      structure and accessibility.

PMID- 12504012
TI  - Target immunity during Mu DNA transposition. Transpososome assembly and DNA
      looping enhance MuA-mediated disassembly of the MuB target complex.
AB  - The Mu transpososome can distinguish between proximal and distal DNA during the
      selection of a site for transposition. This phenomenon, termed target immunity,
      involves MuA-stimulated removal of MuB oligomers from sites near the Mu genome.
      Using a combination of ensemble and single-molecule fluorescence methods, we show
      that the MuA tetramer can stably associate with the DNA-bound MuB oligomer and is
      more efficient than monomeric MuA at stimulating the dissociation of MuB from
      DNA. In addition, we demonstrate that DNA looping is essential for efficient
      disassembly of the MuB oligomer. We propose a model in which the MuA tetramer
      forms a multivalent complex with the MuB oligomer and catalyzes the processive
      removal of MuB from DNA.

PMID- 12504013
TI  - Leaky Scid phenotype associated with defective V(D)J coding end processing in
      Artemis-deficient mice.
AB  - Radiosensitive severe combined immune deficiency in humans results from mutations
      in Artemis, a protein which, when coupled with DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs), possesses DNA hairpin-opening activity in vitro.
      Here, we report that Artemis-deficient mice have an overall phenotype similar to
      that of DNA-PKcs-deficient mice-including severe combined immunodeficiency
      associated with defects in opening and joining V(D)J coding hairpin ends and
      increased cellular ionizing radiation sensitivity. While these findings strongly
      support the notion that Artemis functions with DNA-PKcs in a subset of NHEJ
      functions, differences between Artemis- and DNA-PKcs-deficient phenotypes, most
      notably decreased fidelity of V(D)J signal sequence joining in DNA-PKcs-deficient
      but not Artemis-deficient fibroblasts, suggest additional functions for DNA-PKcs.
      Finally, Artemis deficiency leads to chromosomal instability in fibroblasts,
      demonstrating that Artemis functions as a genomic caretaker.

PMID- 12504014
TI  - Transcriptional activators stimulate DNA repair.
AB  - To counteract the deleterious effects of genotoxic injury, cells have set up a
      sophisticated network of DNA repair pathways. We show that Gal4-VP16 and RAR
      transcriptional activators stimulate nucleotide excision repair (NER). This DNA
      repair activation is not coupled to transcription since it occurs in Cockayne
      syndrome cells (which are transcription-coupled repair deficient) and is observed
      in vitro in the presence of alpha-amanitin and in the absence of the basal
      transcription factors. Using a reconstituted dual incision assay, we also show
      that binding of activators to their cognate sequences induces a local chromatin
      remodeling mediated by ATP-driven chromatin remodeling and acetyltransferase
      activities to facilitate DNA repair.

PMID- 12504015
TI  - The CD8alpha gene locus is regulated by the Ikaros family of proteins.
AB  - Ikaros family members are important regulatory factors in lymphocyte development.
      Here we show that Ikaros may play an important role in CD4 versus CD8 lineage
      commitment decisions by demonstrating: (1) that it binds to regulatory elements
      in the endogenous CD8alpha locus in vivo using thymocyte chromatin
      immunoprecipitations, (2) that Ikaros suppresses position effect variegation of
      transgenes driven by CD8 regulatory elements, and (3) that mice with reduced
      levels of Ikaros and Aiolos show an apparent increase in CD4 populations with
      immature phenotype, i.e., cells that failed to activate the CD8alpha gene locus.
      We propose that Ikaros family members function as activators of the CD8alpha gene
      locus and that their associated activities are critical for appropriate chromatin
      remodeling transitions during thymocyte differentiation and lineage commitment.

PMID- 12504016
TI  - Cellular RNA-dependent RNA polymerase involved in posttranscriptional gene
      silencing has two distinct activity modes.
AB  - Recent genetic data suggest that proteins homologous to a plant RNA-dependent RNA
      polymerase (RdRP) play a central role in posttranscriptional gene silencing
      (PTGS) in many organisms. We show here that purified recombinant protein QDE-1, a
      genetic component of PTGS ("quelling") in the fungus Neurospora crassa, possesses
      RNA polymerase activity in vitro. The full-length enzyme and its enzymatically
      active C-terminal fragment perform two different reactions on single-stranded RNA
      templates, synthesizing either extensive RNA chains that form template-length
      duplexes or approximately 9-21-mer complementary RNA oligonucleotides scattered
      along the entire template. QDE-1 supports both de novo and primer-dependent
      initiation mechanisms. These results suggest that several distinct activities of
      cell-encoded RdRPs can be employed for efficient PTGS in vivo.

PMID- 12504017
TI  - The RNA polymerase II CTD kinase CTDK-I affects pre-mRNA 3'
      cleavage/polyadenylation through the processing component Pti1p.
AB  - There are several kinases in Saccharomyces cerevisiae that phosphorylate the CTD
      of RNA polymerase II, but specific and distinct functions of the phospho-CTDs
      generated by the different kinases are not well understood. A genetic screen for
      suppressors of loss of yeast CTD kinase I (CTDK-I) function (by deletion of the
      catalytic subunit gene CTK1) identified PTI1, a potential 3'
      cleavage/polyadenylation factor. Genetic and physical interactions connect Pti1p
      to components of CF IA and CF II/CPF, and mutations of PTI1 or CTK1 affect 3'
      cleavage site choice and transcript abundance of particular genes. Therefore, one
      important function of the CTDK-I-generated phospho-CTD appears to be the coupling
      of transcription to 3' processing of pre-mRNAs by a Pti1p-containing complex.

PMID- 12504018
TI  - A role for chromatin remodeling in transcriptional termination by RNA polymerase
      II.
AB  - Chromatin remodeling can facilitate the recruitment of RNA polymerase II (Pol II)
      to targeted promoters, as well as enhancing the level of transcription. Here, we
      describe a further key role for chromatin remodeling in transcriptional
      termination. Using a genetic screen in S. pombe, we identified the CHD-Mi2 class
      chromatin remodeling ATPase, Hrp1, as a termination factor. In S. cerevisiae, we
      show that transcriptional termination and chromatin structure at the 3' ends of
      three genes all depend on the activity of the Hrp1 homolog, Chd1p, either alone
      or redundantly with the ISWI ATPases, Isw1p, and Isw2p. We suggest that chromatin
      remodeling of termination regions is a necessary prelude to efficient Pol II
      termination.

PMID- 12504019
TI  - Looping and interaction between hypersensitive sites in the active beta-globin
      locus.
AB  - Eukaryotic transcription can be regulated over tens or even hundreds of
      kilobases. We show that such long-range gene regulation in vivo involves spatial
      interactions between transcriptional elements, with intervening chromatin looping
      out. The spatial organization of a 200 kb region spanning the murine beta-globin
      locus was analyzed in expressing erythroid and nonexpressing brain tissue. In
      brain, the globin cluster adopts a seemingly linear conformation. In erythroid
      cells the hypersensitive sites of the locus control region (LCR), located 40-60
      kb away from the active genes, come in close spatial proximity with these genes.
      The intervening chromatin with inactive globin genes loops out. Moreover, two
      distant hypersensitive regions participate in these interactions. We propose that
      clustering of regulatory elements is key to creating and maintaining active
      chromatin domains and regulating transcription.

PMID- 12504020
TI  - Dynamics of enhancer-promoter communication during differentiation-induced gene
      activation.
AB  - We analyzed the order of recruitment of factors to the HNF-4alpha regulatory
      regions upon the initial activation of the gene during enterocyte
      differentiation. An initially independent assembly of regulatory complexes at the
      proximal promoter and the upstream enhancer regions was followed by the tracking
      of the entire DNA-protein complex formed on the enhancer along the intervening
      DNA until it encountered the proximal promoter. This movement correlated with a
      unidirectional spreading of histone hyperacetylation. Transcription initiation
      coincided with the formation of a stable enhancer-promoter complex and remodeling
      of the nucleosome situated at the transcription start site. The results provide
      experimental evidence for the involvement of a dynamic process culminating in
      enhancer-promoter communication during long-distance gene activation.

PMID- 12504021
TI  - Promoter activation by enhancer-dependent and -independent loading of activator
      and coactivator complexes.
AB  - Activation of the pDbeta1 promoter at the TCRbeta locus requires a functional
      distal enhancer, Ebeta. Here, we have analyzed the mechanism of promoter
      activation in thymocytes from mice containing or lacking Ebeta. We found that
      pDbeta1 shows a complex profile of transcription factor and chromatin remodeling
      complex occupancy even at Ebeta(-) alleles. The presence of Ebeta, however,
      results in a few specific changes in factor occupancy at the promoter. These
      differences correlate with localized alterations in histone modifications and in
      the recruitment of the basal transcriptional machinery. In addition, Ebeta is
      also bound by CBP and Pol II, suggesting a mechanism for delivery of a holoenzyme
      complex to the pDbeta1 promoter. These results illustrate a specialized, long
      range function of an enhancer in the hierarchical events that regulate assembly
      of a cell type-specific promoter.

PMID- 12504022
TI  - Maf1 is an essential mediator of diverse signals that repress RNA polymerase III
      transcription.
AB  - Maf1 is a putative repressor of RNA polymerase (pol) III transcription that is
      conserved from yeast to humans. Here we show that Maf1 is a common component of
      multiple signaling pathways in S. cerevesiae that sense changes in the cellular
      environment and repress pol III transcription. Signaling pathways activated in
      response to rapamycin-induced nutrient limitation, DNA damage, and secretory
      pathway defects all require Maf1 in order to affect pol III transcriptional
      repression. In addition, Maf1 was required for repression of pol III
      transcription during the normal yeast growth cycle. Biochemical studies
      identified the initiation factor TFIIIB as a target of Maf1-dependent repression
      and revealed a defect in TFIIIB-DNA complex assembly under repressing conditions.

PMID- 12504023
TI  - Template switching by RNA polymerase II in vivo. Evidence and implications from a
      retroviral system.
AB  - Transfection of retrovirus packaging cells with linear DNA from a retroviral
      vector missing the 3' long terminal repeat (3' LTR) results in production of
      infectious virus. Analysis of the newly formed proviruses indicates that
      restoration of the 3' LTR sequences necessary for reverse transcription and
      integration occurred due to end-to-end template switching by mammalian RNA
      polymerase II (RNAP II) in the packaging cells. These observations argue that
      RNAP II can utilize double-strand breaks and gaps in DNA to generate
      "recombinant" transcripts in vivo and suggest a mechanism for mutation and
      recombination of retroviruses.

PMID- 12504024
TI  - Drosophila MUS312 interacts with the nucleotide excision repair endonuclease MEI
      9 to generate meiotic crossovers.
AB  - MEI-9 is the Drosophila homolog of the human structure-specific DNA endonuclease
      XPF. Like XPF, MEI-9 functions in nucleotide excision repair and interstrand
      crosslink repair. MEI-9 is also required to generate meiotic crossovers, in a
      function thought to be associated with resolution of Holliday junction
      intermediates. We report here the identification of MUS312, a protein that
      physically interacts with MEI-9. We show that mutations in mus312 elicit a
      meiotic phenotype identical to that of mei-9 mutants. A missense mutation in mei
      9 that disrupts the MEI-9-MUS312 interaction abolishes the meiotic function of
      mei-9 but does not affect the DNA repair functions of mei-9. We propose that
      MUS312 facilitates resolution of meiotic Holliday junction intermediates by MEI
      9.

PMID- 12504025
TI  - NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1
      binding and SCF ligases.
AB  - Cullin proteins assemble a large number of RING E3 ubiquitin ligases and regulate
      various physiological processes. Covalent modification of cullins by the
      ubiquitin-like protein NEDD8 activates cullin ligases through an as yet undefined
      mechanism. We show here that p120(CAND1) selectively binds to unneddylated CUL1
      and is dissociated by CUL1 neddylation. CAND1 formed a ternary complex with CUL1
      and ROC1. CAND1 dissociated SKP1 from CUL1 and inhibited SCF ligase activity in
      vitro. Suppression of CAND1 in vivo increased the level of the CUL1-SKP1 complex.
      We suggest that by restricting SKP1-CUL1 interaction, CAND1 regulated the
      assembly of productive SCF ubiquitin ligases, allowing a common CUL1-ROC core to
      be utilized by a large number of SKP1-F box-substrate subcomplexes.

PMID- 12504026
TI  - CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3
      ligase complex.
AB  - The SCF ubiquitin E3 ligase regulates ubiquitin-dependent proteolysis of many
      regulatory proteins such as p27(Kip1), IkappaB, and beta-catenin. We report the
      isolation of a CUL1 binding protein, p120(CAND1). We found the majority of CUL1
      is in a complex with CAND1 and ROC1 independent of SKP1 and F box protein SKP2.
      Both in vivo and in vitro, CAND1 prevents the binding of SKP1 and SKP2 to CUL1
      while dissociation of CAND1 from CUL1 promotes the reverse reaction. Neddylation
      of CUL1 or the presence of SKP1 and ATP causes CAND1 dissociation. Our data
      suggest that CAND1 regulates the formation of the SCF complex, and its
      dissociation from CUL1 is coupled with the incorporation of F box proteins into
      the SCF complex, causing their destabilization.

PMID- 12504027
TI  - Activation of the Drosophila MLK by ceramide reveals TNF-alpha and ceramide as
      agonists of mammalian MLK3.
AB  - Mixed lineage kinases (MLKs) are MAPKKK members that activate JNK and reportedly
      lead to cell death. However, the agonist(s) that regulate MLK activity remain
      unknown. Here, we demonstrate ceramide as the activator of Drosophila MLK (dMLK)
      and identify ceramide and TNF-alpha as agonists of mammalian MLK3. dMLK and MLK3
      are activated by a ceramide analog and bacterial sphingomyelinase in vivo,
      whereas a low nanomolar concentration of natural ceramide activates them in
      vitro. Specific inhibition of dMLK and MLK3 significantly attenuates activation
      of JNK by ceramide in vivo without affecting ceramide-induced p38 or ERK
      activation. In addition, TNF-alpha also activates MLK3 and evidently leads to JNK
      activation in vivo. Thus, the ceramide serves as a common agonist of dMLK and
      MLK3, and MLK3 contributes to JNK activation induced by TNF-alpha.

PMID- 12504028
TI  - Optimizing combined modality therapy for Hodgkin's disease.

PMID- 12504029
TI  - The holy grail of radiation oncology: lessons learned from hyperthermia.

PMID- 12504030
TI  - Nuclear medicine imaging to predict response to radiotherapy: a review.
AB  - PURPOSE: To review available literature on positron emission tomography (PET) and
      single photon emission computerized tomography (SPECT) for the measurement of
      tumor metabolism, hypoxia, growth factor receptor expression, and apoptosis as
      predictors of response to radiotherapy. METHODS AND MATERIALS: Medical literature
      databases (Pubmed, Medline) were screened for available literature and critically
      analyzed as to their scientific relevance. RESULTS: Studies on 18F
      fluorodeoxyglucose PET as a predictor of response to radiotherapy in head-and
      neck carcinoma are promising but need confirmation in larger series. 18F
      fluorothymine is stable in human plasma, and preliminary clinical data obtained
      with this marker of tumor cell proliferation are promising. For imaging tumor
      hypoxia, novel, more widely available radiopharmaceuticals with faster
      pharmacokinetics are mandatory. Imaging of ongoing apoptosis and growth factor
      expression is at a very early stage, but results obtained in other domains with
      radiolabeled peptides appear promising. Finally, for most of the tracers
      discussed, validation against a gold standard is needed. CONCLUSION: Optimization
      of the pharmacokinetics of relevant radiopharmaceuticals as well as validation
      against gold-standard tests in large patient series are mandatory if PET and
      SPECT are to be implemented in routine clinical practice for the purpose of
      predicting response to radiotherapy.

PMID- 12504031
TI  - High cyclooxygenase-2 expression is related with distant metastasis in cervical
      cancer treated with radiotherapy.
AB  - PURPOSE: The cyclooxygenase (COX)-2 enzyme has been shown to have an important
      role in carcinogenesis and apoptosis in various types of cancer. The purpose of
      this study was to evaluate the relationship between local recurrence or distant
      metastasis and COX-2 expression and apoptosis in cervical cancer patients treated
      with radical radiotherapy (RT). METHODS AND MATERIALS: Twenty-two patients who
      were diagnosed with cervical cancer were enrolled in this study. All patients
      were treated with radical RT (external beam RT plus brachytherapy) at Seoul
      National University Hospital. The formalin-fixed, paraffin-embedded tissues of 11
      patients who developed local recurrence (n = 3) or distant metastasis (n = 8)
      were compared with those of other patients who were disease free. Prognostic
      factors, including tumor size, lymph node metastatic status, and stage, were well
      balanced between the two groups. COX-2 expression was determined
      immunohistochemically, and apoptosis was assessed using in situ DNA nick end
      labeling (TUNEL)-based methods. RESULTS: COX-2 expression was stronger in the
      local recurrence and distant metastasis patients than in those free of disease.
      COX-2 expression was shown to have a statistically significant influence on
      treatment failure by the Mann-Whitney U test (p = 0.015) and the Mantel-Haenszel
      chi-square test (p = 0.015), but its distribution did not correlate with
      apoptosis. Among the clinicopathologic factors, including stage, lymph node
      metastatic status, and tumor size, lymph node metastatic status was found to
      closely correlate with COX-2 expression by the Mann-Whitney U test (p = 0.045)
      and Mantel-Haenszel chi-square test (p = 0.065). CONCLUSION: COX-2 is believed to
      be one of the important factors associated with lymph node involvement and
      treatment failure. Our results suggest that inhibiting COX-2 may decrease
      treatment failure in cervical cancer treated with RT, and that COX-2 inhibitor
      administration may play an adjuvant role in cervical cancer treatment.

PMID- 12504032
TI  - Cyclooxygenase-2 (COX-2) expression in locally advanced cervical cancer patients
      undergoing chemoradiation plus surgery.
AB  - PURPOSE: To investigate whether cyclooxygenase-2 (COX-2) could be a marker of
      clinical outcome in cervical cancer patients undergoing concomitant
      chemoradiation plus surgery. METHODS AND MATERIALS: The study included 33 locally
      advanced cervical cancer patients; all underwent neoadjuvant chemoradiation, and
      responsive patients underwent radical surgery. Immunohistochemistry was performed
      with rabbit antiserum against COX-2. RESULTS: COX-2 integrated density values
      (IDVs) in the tumor component ranged from 1.4 to 72.3 (median 15.0); in stromal
      inflammatory cells, COX-2 IDVs ranged from 1.4 to 96.0 (median 16.0). A
      statistically significant inverse relation was found between the COX-2 IDVs of
      the tumor vs. the stromal inflammatory component (r = -0.52, p = 0.0017). When
      the ratio between COX-2 IDV in the tumor vs. the stromal compartment was <or=1,
      it was considered to indicate cervical tumor with COX-2 expression in the tumor
      component lower or equivalent to COX-2 expression in the stroma. According to the
      chosen cutoff value, 17 (51.5%) of 33 were scored as having a high (>1)
      tumor/stroma COX-2 IDV ratio. Patients with a high tumor/stroma COX-2 IDV ratio
      had a shorter disease-free survival than did those with a low tumor/stroma COX-2
      IDV ratio (p = 0.030). Similarly, those with a high tumor/stroma COX-2 IDV ratio
      had a shorter overall survival (p = 0.033). CONCLUSION: The assessment of COX-2
      status in both the tumor and the stromal compartment could provide additional
      information in the prognostic characterization of cervical cancer patients
      administered concomitant chemoradiation plus surgery.

PMID- 12504033
TI  - PET-guided IMRT for cervical carcinoma with positive para-aortic lymph nodes-a
      dose-escalation treatment planning study.
AB  - PURPOSE: To evaluate a treatment planning method for dose escalation to the para
      aortic lymph nodes (PALNs) based on positron emission tomography (PET) with
      intensity-modulated radiotherapy (IMRT) for cervical cancer patients with PALN
      involvement. One goal of this process was not to modify the traditional treatment
      of the pelvic region. METHODS AND MATERIALS: PET images for 4 cervical cancer
      patents with PALN involvement were registered with their corresponding CT scans.
      Positive PALNs were identified on PET images, and the surrounding critical
      structures were delineated on CT images. The treatment machine central axis (CAX)
      was placed at the level of the L4-L5 vertebral body interspace. There were two
      distinct treatment regions: the para-aortic bed superior to the CAX and the whole
      pelvis region inferior to the CAX. IMRT was used for treatment planning of PALN
      bed irradiation. The positive PALNs identified on PET images were defined as the
      gross target volume, and the para-aortic bed was defined as the clinical target
      volume. The radiation doses were escalated from the conventional 45 Gy to 59.4 Gy
      for the gross target volume and 50.4 Gy for the clinical target volume in 33
      fractions. The pelvis area was treated with conventional treatment methods, AP-PA
      beams to 50.4 Gy in 28 fractions with a brachytherapy implant boost. The
      placement of the CAX allowed the two treatment regions to be abutted using the
      treatment machine's independent jaws. RESULTS: Dose escalation to positive PALNs,
      as identified on PET images, and the PALN bed is feasible with IMRT. Treatment
      plans for 4 patients revealed that escalated prescription doses could be
      delivered to target volumes while maintaining acceptable doses to the surrounding
      critical structures. Strategic placement of the treatment isocenter allows the
      IMRT region (PALN bed) and whole pelvis fields to be treated with a relatively
      uniform dose distribution in the abutment region. CONCLUSION: This study
      indicates that PET-guided IMRT could be used in a clinical trial in an attempt to
      escalate doses delivered to patients with cervical cancer who have positive
      PALNs.

PMID- 12504034
TI  - Analysis of in-field control and late toxicity for adults with early-stage
      Hodgkin's disease treated with chemotherapy followed by radiotherapy.
AB  - PURPOSE: We analyzed in-field (IF) control in adults with early-stage Hodgkin's
      disease who received chemotherapy followed by radiotherapy (RT) in terms of the
      (1) chemotherapeutic regimen used and number of cycles delivered, (2) response to
      chemotherapy, and (3) initial tumor size. Cardiac toxicity and second
      malignancies, particularly the incidence of solid tumors in terms of the RT field
      size treated, were also examined. METHODS AND MATERIALS: From 1980 to 1995, 286
      patients ranging in age from 16 to 88 years (median: 28 years) with Ann Arbor
      clinical Stage I or II Hodgkin's disease underwent chemotherapy followed 3 to 4
      weeks later by RT. There were 516 nodal sites measuring 0.5 to 19.0 cm at the
      start of chemotherapy, including 134 cases of bulky mediastinal disease. NOVP,
      MOPP, ABVD, CVPP/ABDIC, and other chemotherapeutic regimens were given to 161,
      67, 19, 18, and 21 patients, respectively. Patients received 1-8 (median: 3)
      cycles of induction chemotherapy. All 533 gross nodal and extranodal sites of
      disease were included in the RT fields. The median prescribed RT dose for gross
      disease was 40.0 Gy given in 20 daily 2.0-Gy fractions. There was little
      variation in the RT dose. Eighty-five patients were treated with involved-field
      or regional RT (to one side of the diaphragm), and 201 patients were treated with
      extended-field RT (to both sides of the diaphragm), based on the protocol on
      which they were enrolled. RESULTS: Follow-up of surviving patients ranged from
      1.3 to 19.9 years (median: 7.4 years). Based on a review of simulation films,
      there were 16 IF, 8 marginal, and 15 out-of-field recurrences. The
      chemotherapeutic regimen used and the number of cycles of chemotherapy delivered
      did not significantly affect IF control. IF control also did not significantly
      depend on the response to induction chemotherapy. In cases where there was a
      confirmed or unconfirmed complete response as opposed to a partial response or
      stable disease in response to induction chemotherapy for bulky nodal disease, the
      5-year IF control rates were 99% and 92%, respectively (p = 0.0006). The 15-year
      actuarial risks of coronary artery disease requiring surgical intervention and of
      solid tumors were 4.1% and 16.8%, respectively. There was a trend toward a
      greater risk of solid tumors in patients who received extended-field RT rather
      than involved-field or regional RT (p = 0.08). CONCLUSIONS: In patients with
      nonbulky disease, induction chemotherapy followed by RT to a median dose of 40.0
      Gy resulted in excellent IF control, regardless of the chemotherapeutic regimen
      used, the fact that only 1-2 cycles of chemotherapy were delivered, and the
      response to chemotherapy. There was a trend toward a higher incidence of solid
      tumors in patients who received consolidation RT to both sides rather than only
      one side of the diaphragm. Ongoing Phase III trials will help clarify whether
      lower RT doses and smaller RT fields after chemotherapy can maintain the IF
      control seen in our study, but with a lower incidence of late complications in
      patients with Stage I or II Hodgkin's disease.

PMID- 12504035
TI  - Stage I and II aggressive B-cell lymphomas of the head and neck: radiotherapy
      alone as a treatment option and the usefulness of the new prognostic index B
      ALPS.
AB  - PURPOSE: To evaluate the outcome according to treatment modality and prognostic
      factors in clinical Stage I and II intermediate- or high-grade B-cell lymphomas
      of the head and neck. METHODS AND MATERIALS: We analyzed 155 patients treated
      between 1983 and 1997, excluding those with the Working Formulation low-grade
      lymphomas. Of these patients, 88 had Stage I and 67 had Stage II disease. Forty
      one patients were treated with radiotherapy (RT) alone, and 114 patients were
      treated with a combination of RT and chemotherapy. Most of the chemotherapy
      regimens included anthracycline derivatives. More patients with Stage I disease
      and more patients with poor performance status were treated with RT alone. The
      treatment results were evaluated according to the new prognostic index B-ALPS,
      consisting of tumor bulk, age, lactate dehydrogenase level, performance status,
      and stage. RESULTS: The 5-year overall and failure-free survival rate was 71.5%
      and 68.3%, respectively, for all 155 patients. The 5-year survival rate was 67%
      for those treated with RT alone and 73% for those treated with radiochemotherapy
      (p = 0.13). Among the various potential prognostic factors, age >60 years, World
      Health Organization performance status 2-4, and tumor size >or=6 cm were
      associated with poorer survival. The 5-year survival rate was 82% for those with
      no or one B-ALPS factor, 66% for those with two factors, and 49% for those with
      three or more factors (p <0.0001). The B-ALPS index appeared to predict the
      prognosis of these patients better than did the International Prognostic Index.
      No single prognostic factor was useful to identify patient groups more suitable
      to treatment with RT alone, but in patients with two B-ALPS risk factors, those
      treated with radiochemotherapy had a better survival rate and tended to have a
      better failure-free survival rate than those treated with RT alone. CONCLUSION: A
      proportion of patients with clinical Stage I or II head-and-neck B-cell lymphoma
      may be successfully treated with RT alone. B-ALPS is a useful prognostic index in
      this disease.

PMID- 12504036
TI  - Evidence-based estimate of appropriate radiotherapy utilization rate for prostate
      cancer.
AB  - PURPOSE: Current estimates of the proportion of cancer patients who will require
      radiotherapy (RT) are based almost entirely on expert opinion. The objective of
      this study was to use an evidence-based approach to estimate the proportion of
      incident cases of prostate cancer that should receive RT at any point in the
      evolution of the illness. METHODS AND MATERIALS: A systematic review of the
      literature was undertaken to identify indications for RT for prostate cancer and
      to ascertain the level of evidence that supported each indication. An
      epidemiologic approach was then used to estimate the incidence of each indication
      for RT in a typical North American population of prostate cancer patients. The
      effect of sampling error on the estimated appropriate rate of RT was calculated
      mathematically, and the effect of systematic error using alternative sources of
      information was estimated by sensitivity analysis. RESULTS: It was estimated that
      61.2% +/- 5.6% of prostate cancer cases develop one or more indications for RT at
      some point in the course of the illness. The plausible range for this rate was
      57.3%-69.8% on sensitivity analysis. Of all prostate cancer patients, 32.2% +/-
      3.8% should receive RT in their initial treatment and 29.0% +/- 4.1% later for
      recurrence or progression. The proportion of cases that ever require RT is risk
      grouping dependent; 43.9% +/- 2.2% in low-risk disease, 68.7% +/- 3.5% in
      intermediate-risk disease; and 79.0% +/- 3.8% in high-risk locoregional disease.
      For metastatic disease, the predicted rate was 66.4% +/- 0.3%. CONCLUSION: This
      method provides a rational starting point for the long-term planning of radiation
      services and for the audit of access to RT at the population level. By completing
      such evaluations in major cancer sites, it will be possible to estimate the
      appropriate RT rate for the cancer population as a whole.

PMID- 12504037
TI  - Clinical utility of endorectal MRI in determining PSA outcome for patients with
      biopsy Gleason score 7, PSA <or=10, and clinically localized prostate cancer.
AB  - PURPOSE: Although the optimal management for patients with high-grade clinically
      localized prostate cancer is undefined, radical prostatectomy (RP) or external
      beam radiotherapy (EBRT) is performed. The clinical utility of the pretreatment
      prostrate-specific antigen (PSA) level (<or=10 and >10 ng/mL) and endorectal MRI
      (erMRI) stage (T3 vs. T2) to stratify PSA outcome after RP in these patients was
      evaluated. METHODS AND MATERIALS: erMRI was performed in 147 men with biopsy
      Gleason score >or=7 and 1992 AJCC clinical Stage T1c or T2a disease before RP.
      Enumerations of the biopsy and prostatectomy Gleason scores, pathologic stage,
      and margin status were performed for each pretreatment group on the basis of
      erMRI findings and PSA level. Comparisons were made using a chi-square metric.
      The median follow-up was 4.5 years (range 1-10 years). Comparisons of the
      actuarial freedom from PSA failure (bNED) were made using the log-rank test.
      RESULTS: erMRI Stage T2 and T3 disease was found in 132 and 15 patients,
      respectively. On stratification by PSA level, patients with erMRI T3 disease had
      similar bNED outcomes (p = 0.46), regardless of the PSA level. The 3-year bNED
      rate was 82%, 64%, and 25% (p <0.0001) for Group 1 (erMRI T2 and PSA <or=10
      ng/mL), Group 2 (erMRI T2 and PSA >10 ng/mL), and Group 3 (erMRI T3 with any PSA
      level), respectively. The rates of prostatectomy T3 disease, biopsy and
      prostatectomy Gleason score 8-10, and positive surgical margins were
      significantly higher (p <or=0.007) in Group 3, followed by Group 2 and were
      lowest in Group 1. When considering only the patients with biopsy Gleason score 7
      (n = 110), the 3-year bNED rate was 83%, 63%, and 28% (p trend <0.0001) for
      Groups 1, 2, and 3, respectivel. CONCLUSION: In the setting of biopsy Gleason
      score >or=7, PSA <or=10 ng/mL, and clinically localized disease, local therapy
      alone may be adequate for patients with erMRI T2 disease. On the other hand,
      these data suggest that more aggressive therapy may be warranted in patients with
      erMRI T3 disease. Given the survival benefit established for patients with
      locally advanced prostate cancer treated with EBRT and androgen suppression
      therapy compared with EBRT alone, erMRI staging may help identify patients with
      high biopsy Gleason score and clinically localized disease who may benefit most
      from treatment with EBRT and hormonal therapy as opposed to EBRT alone.

PMID- 12504038
TI  - Late morbidity profiles in prostate cancer patients treated to 79-84 Gy by a
      simple four-field coplanar beam arrangement.
AB  - PURPOSE: To describe the frequency and magnitude of late GI and GU morbidity in
      prostate cancer patients treated to high dose levels with a simple three
      dimensional conformal technique. METHODS AND MATERIALS: A total of 156
      intermediate- and high-risk patients were treated between January 1, 1992 and
      February 28, 1999 with a simple four-field three-dimensional conformal technique
      to 79-84 Gy. All patients were treated with a four-field conformal technique; the
      prostate received 82 Gy and the seminal vesicles and periprostatic tissue 46 Gy.
      GI and GU toxicity was scored according to the Radiation Therapy Oncology
      Group/European Organization for Research and Treatment of Cancer Late Morbidity
      Grading Scale and compared using Kaplan-Meier estimates. RESULTS: The late Grade
      2 GI complication rate was 9% and 38% at 3 years for patients treated with and
      without rectal blocking, respectively (p = 0.0004). No Grade 3 late GI
      complications developed. The rate of Grade 2 late GU complications was 5%, 8%,
      and 12% at 12, 24, and 36 months, respectively. The Grade 3 late GU complication
      rate was 2% at 36 months. These differences were not statistically significant.
      CONCLUSION: The treatment method described is a simple four-field conformal
      technique that can be easily implemented in the general radiation community. A
      dose of 79-84 Gy can be safely delivered to the prostate, with a 9% rate of late
      Grade 2 GI, 12% rate of late Grade 2 GU, and 2% rate of late Grade 3 GU
      complications.

PMID- 12504039
TI  - Locoregionally advanced carcinoma of the oropharynx: conventional radiotherapy
      vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and
      chemotherapy--a multicenter randomized trial.
AB  - PURPOSE: To compare conventional fractionation radiation therapy (RT), Arm A, vs.
      split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional
      fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival
      and toxicity for advanced, unresectable epidermoid tumors of oropharynx. METHODS
      AND MATERIALS: Between January 1993 and June 1998, 192 previously untreated
      patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1
      and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01).
      For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered
      in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor
      and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an
      interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4
      Gy, a 2-week split was planned; after the split, RT was resumed with the same
      modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA
      75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling
      every 28 days (at 1st, 5th, and 9th week). RESULTS: No statistically significant
      difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B
      vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically
      significant difference in terms of event-free survival (p = 0.196): 20% for Arm
      A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the
      contrary, the 2-year disease-free survival was significantly different among the
      three arms (p = 0.022), with a superiority for Arm C. At 24 months, the
      proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and
      20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis
      than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT
      related acute toxicity, apart from 1 case of fatal nephrotoxicity, only
      hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health
      Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more
      G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although
      significant sequelae were relatively uncommon, and mucosal sequelae were most
      commonly transient. The occurrence of persistent G3 xerostomia was comparable in
      all three treatment arms. CONCLUSIONS: The combination of simultaneous CT and RT
      with the regimen of this trial is better than RT alone in advanced oropharyngeal
      squamous-cell carcinomas, by increasing disease-free survival. This improvement,
      however, did not translate into an overall survival improvement, and was
      associated with a higher incidence of acute morbidity.

PMID- 12504040
TI  - Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy
      with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma:
      comparison of LENT/SOMA, RTOG/EORTC, and NCI-CTC scoring systems.
AB  - PURPOSE: To prospectively assess 5-year late toxicity in patients treated by
      concomitant radiochemotherapy for locally advanced oropharynx carcinoma using
      three different toxicity scales. METHODS AND MATERIALS: A total of 226 patients
      were entered in a Phase III multicenter, randomized trial comparing radiotherapy
      alone (70 Gy in 35 fractions: Arm A) with concomitant radiochemotherapy (70 Gy in
      35 fractions with three cycles of a 4-day regimen containing carboplatin and 5
      fluorouracil: Arm B). Five living patients, free of local or distant recurrences,
      could not be evaluated for late toxicity. Forty-four patients were eligible for
      late toxicity with a median follow-up of 5 years. Late toxicity was evaluated by
      the radiation oncologist using a large questionnaire containing 120 mixed items
      of three scales (NCI-CTC, LENT/SOMA, and RTOG). The data were then transposed on
      separate scales using corresponding grades. RESULTS: The 5-year overall survival
      rate was 22% in Arm B and 16% in Arm A (p = 0.05). The 5-year locoregional
      control rate was 48% in Arm B and 25% in Arm A (p = 0.002). The spinal cord was
      not affected by the concomitant adjunct of chemotherapy, and no deaths were
      caused by late toxicity. Using the three late toxicity scales, 100% of the
      patients treated with the combined modality (Arm B) developed one or more late
      complications vs. 94% in the radiotherapy-alone arm (Arm A). The difference was
      not statistically significant. The most commonly damaged organs (all Grade 1-4)
      were the salivary glands (100% in Arm B vs. 82% in Arm A, p <0.05), skin (78% vs.
      47%, p <0.05), teeth (67% vs. 18%, p <0.05), mucosa (59% vs. 63% p = not
      significant), and mandible (44% vs. 12%, p <0.05). One or more Grade 3-4
      complications occurred in 82% of the patients in Arm B vs. 47% in Arm A (p =
      0.02) but concerned only the teeth. The correlation between the RTOG and
      LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1
      4 toxicity (near 30%). The transposability of a patient's symptoms was
      significantly greater using the LENT/SOMA or RTOG/EORTC scaling systems than
      using the NCI-CTC system. CONCLUSION: Concomitant radiochemotherapy increased
      overall survival and locoregional control rates. The difference between the two
      treatment groups for Grade 3-4 complications was only significant for the teeth.
      The late toxicity assessment of a treatment may depend on the toxicity scale
      used. The LENT/SOMA scale seems to be the most accurate scale, but most of the
      score results were not concordant with those obtained with other scales. The
      results of this study confirm the necessity of using a common late toxicity scale
      in clinical trials.

PMID- 12504041
TI  - Comparison of intensity-modulated radiosurgery with gamma knife radiosurgery for
      challenging skull base lesions.
AB  - PURPOSE: To quantitatively compare intensity-modulated radiosurgery (IMRS) using
      3-mm mini-multileaf collimation with gamma knife radiosurgery (GKRS) plans for
      irregularly shaped skull base lesions in direct proximity to organs at risk
      (OAR). METHODS AND MATERIALS: Ten challenging skull base lesions originally
      treated with GKRS were selected for comparison with IMRS using inverse treatment
      planning and 3-mm mini-multileaf collimation operating in step-and-shoot delivery
      mode. The lesions ranged in volume from 1.6 to 32.2 cm(3) and were treated with 9
      20 GK isocenters (mean 13.2). The IMRS plans were designed with the intent to, at
      minimum, match the GKRS plans with regard to OAR sparing and target coverage. For
      each case, IMRS plans were generated using 9 coplanar, 11 equally spaced
      noncoplanar, and 11 OAR-avoidant noncoplanar beams; the best of these approaches
      with respect to target conformality, sparing of OAR, and maintaining coverage was
      selected for comparison with the original GKRS plan. RESULTS: Assuming no patient
      motion or setup error, IMRS provided comparable target coverage and sparing of
      OAR and an improved conformity index at the prescription isodose contour but
      sometimes less conformity at lower isodose contours compared with the actual GKRS
      plan. All IMRS plans produced less target dose heterogeneity and shorter
      estimated treatment times compared with the GKRS plans. CONCLUSION: Compared with
      GKRS for complex skull base lesions, IMRS plans using a 3-mm mini-multileaf
      collimator achieved comparable or sometimes improved target coverage, conformity,
      and critical structure sparing with shorter estimated treatment times.

PMID- 12504042
TI  - Predictive value of dose-volume histogram parameters for predicting radiation
      pneumonitis after concurrent chemoradiation for lung cancer.
AB  - PURPOSE: To clarify whether the percentage of pulmonary volume irradiated to >20
      Gy (V20) is related to the incidence and grade of radiation pneumonitis (RP) in
      cases of lung cancer treated with concurrent chemoradiation. METHODS AND
      MATERIALS: The subjects comprised 71 patients with lung cancer who were treated
      with conventionally fractionated definitive concurrent chemoradiation. The
      chemotherapy agents were carboplatin or cisplatin combined with taxane for most
      patients. Radiotherapy was delivered at 1.8-2.0 Gy fractions once daily to a
      total of 48-66 Gy (median 60). We analyzed the relation between RP grade and V20.
      Univariate and multivariate analyses were performed to assess patient- and
      treatment-related factors, including age, gender, smoking history, pulmonary
      function (forced expiratory volume in 1 s), tumor location (upper lobe vs.
      middle/lower lobe), chemotherapy regimen (platinum + taxane vs. other), total
      dose, overall radiation periods in addition to V20. RESULTS: With a median follow
      up of 7.5 months, an RP grade of 0, 1, 2, 3, and 5 was observed in 16, 35, 17, 1,
      and 2 patients, respectively; the corresponding mean V20 values were 20.1%,
      22.0%, 26.3%, 27.0%, and 34.5%. The 6-month cumulative incidence of RP greater
      than Grade 2 was 8.7%, 18.3%, 51%, and 85% in patients with a V20 of <or=20%, 21
      25%, 26-30%, and >or=31%, respectively (p <0.0001). According to both univariate
      and multivariate analyses, V20 was the only factor associated with RP of Grade 2
      or greater. CONCLUSION: The incidence and grade of RP are significantly related
      to the V20 value. Thus, V20 appears to be a factor that can be used to predict RP
      after concurrent chemoradiation for lung cancer.

PMID- 12504043
TI  - Improvement in performance status after erythropoietin treatment in lung cancer
      patients undergoing concurrent chemoradiotherapy.
AB  - PURPOSE: A prospective Phase II trial was carried out to evaluate the
      effectiveness of erythropoietin in improving or maintaining performance status as
      determined by the Karnofsky performance status (KPS) score and hemoglobin (Hb)
      levels in lung cancer patients treated with concurrent chemoradiation (CH-RT).
      METHODS AND MATERIALS: A total of 51 patients with lung cancer (11 with small
      cell, limited stage and 40 with non-small-cell disease, 17 with Stage IIIA and 23
      with Stage IIIB), who underwent three different concurrent CH-RT protocols were
      enrolled. Baseline Hb and KPS values were recorded, as were the nadir Hb and KPS
      values before concurrent CH-RT. The final Hb and KPS values were recorded the
      last week of concurrent CH-RT. An Hb level of <or=11 g/dL before concurrent CH-RT
      was required before receiving erythropoietin. Prognostic factors for KPS
      improvement and survival were assessed by univariate and multivariate studies.
      RESULTS: Of the 51 patients, 47 (92.3%) were men (mean age 63.6 years, range 40
      75). The median baseline KPS score was 80, and the mean baseline Hb was 12.2 +/-
      1.76 g/dL (range 9-16.9). The mean nadir and final Hb value was 9.98 +/- 0.67
      g/dL (range 8.6-11) and 11.33 +/- 1.59 g/dL (range 6.9-14.4), respectively. A
      significant increase was seen in the Hb and KPS score (p <0.05) in the final
      measurements. Differences were found between the final and nadir Hb in the
      predictive value for differences in performance status (p = 0.001). On univariate
      study, pathologic findings (p = 0.0234), weight loss (p = 0.0049), baseline Hb (p
      = 0.0057), and final Hb improvement (p = 0.0237) were prognostic factors for
      survival. Nadir Hb (p = 0.027), final Hb improvement (p = 0.0069), pathologic
      findings (p = 0.0006), and weight loss (p = 0.0001) had significant prognostic
      value for survival in multivariate analysis. CONCLUSION: In this study,
      erythropoietin appears to have a significant, beneficial impact on the KPS and Hb
      of patients undergoing concurrent CH-RT.

PMID- 12504044
TI  - Outcomes and patterns of failure in bronchial carcinoid tumors.
AB  - PURPOSE: To clarify the natural history, prognosis, and treatment failure
      patterns for bronchial carcinoid tumors according to their clinical and
      histopathologic features. METHODS: The charts of 241 patients from our
      institution with bronchial carcinoid tumors were reviewed. Thirty-four patients
      had no follow-up, yielding a study population of 206. Of the 206 patients, 62 had
      atypical carcinoid (AC) and 144 had typical carcinoid (TC) tumors. RESULTS: The 5
      , 10-, and 20-year disease-specific survival rates were lower in patients with AC
      (60.1%, 36.8%, and 28.1%, respectively) than in those with TC (79.0%, 62.9%, and
      38.8%, respectively; p = 0.0002). Predictors of poor outcome included more
      advanced stage (p <0.00001), male gender (p = 0.019), symptoms at presentation (p
      = 0.013), and age >or=60 years (p = 0.02). Stage I AC was associated with a
      median disease-free survival of 96 months compared with 222 months for Stage I TC
      (p = 0.0002) and had an actuarial 22% locoregional failure rate 5 years after
      surgery compared with 6% for Stage I TC (p = 0.022). The disease-free survival
      for Stage II and III AC was worse than that for Stage II or III TC, but the
      difference did not reach statistical significance (p = 0.15). Locoregional
      failure was also prominent in Stage II and III AC. Second malignancies were
      common in patients with bronchial carcinoids (56 of 206 patients). CONCLUSION:
      Stage-for-stage, the outcome is worse for patients with AC than for those with
      TC. Locoregional failure is common after curative resection, even for early-stage
      AC. Second cancers are common in patients with carcinoid tumors.

PMID- 12504045
TI  - Phase II trial of preoperative 3D conformal radiotherapy, protracted venous
      infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound
      staged T3 rectal cancer.
AB  - PURPOSE: CPT-11 sensitizes tumor cells to radiation and in combination therapy
      with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic
      colorectal cancer. We report the results from a Phase II trial of preoperative
      radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal
      cancer. METHODS AND MATERIALS: Between April 1999 and August 2001, 32 patients
      (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven
      adenocarcinoma of the rectum were enrolled in the study. All patients underwent
      endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT
      was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and
      tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT
      11 (50 mg/m(2), Days 1, 8, 15, and 22) and 5-FU (200 mg/m(2) daily, 7 d/wk, Days
      1-33). Surgical resection was performed 6-10 weeks after completing
      chemoradiotherapy. RESULTS: Acute toxicity was frequently observed, and 18
      patients (56%) required either a chemotherapy dose reduction or RT interruption
      of >3 days. One patient withdrew because of diarrhea and abdominal cramping
      (Grade III) after 10 days of treatment. Although no Grade IV toxicity was
      observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores
      (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who
      underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the
      disease of 23 (71%) was downstaged. The average length of hospitalization was
      between 5 and 12 days, with 1 patient staying 33 days. All patients were followed
      for disease-free survival. CONCLUSION: Although associated with frequent acute
      toxicity, the regimen is associated with significant tumor "downstaging."
      Additional patients and longer follow-up are necessary to define the role of this
      regimen fully.

PMID- 12504046
TI  - Sites of local recurrence after surgery, with or without chemotherapy, for rectal
      cancer: implications for radiotherapy field design.
AB  - PURPOSE: To examine the sites of pelvic recurrence in patients with rectal cancer
      previously untreated with radiotherapy to determine the relative frequency and
      location of recurrence within the pelvis. METHODS AND MATERIALS: The records of
      patients with locally recurrent rectal cancer referred to three radiation
      oncology departments between 1984 and 1997 were reviewed. The data collected
      included the date and type of the initial resection and the pathologic findings.
      The site of recurrence within the pelvis, presence of metastasis, and date of
      recurrence were documented. RESULTS: A total of 269 patients were included. Tumor
      had invaded through the muscularis in 74% and involved other organs in 9%. Fifty
      two percent of patients were node positive at initial surgery. The median time to
      local recurrence from surgery was 18 months (range 15-20) and from local
      recurrence to death was 14 months (range 12-17). Both the initial tumor stage and
      the resection type influenced the recurrence location within the pelvis (p
      <0.01). T4 tumors comprised only 9% of initial T stage tumors but accounted for
      38% of anterior central pelvic recurrences (p <0.01). All perineal recurrences
      occurred after abdominoperineal resection. The sites of recurrence within the
      pelvis were the posterior central pelvis (47%) and anastomotic (21%). CONCLUSION:
      If those patients with T4 tumors at presentation were excluded, 89% had local
      recurrence at, or posterior to, the anastomosis. Furthermore, if we exclude both
      patients who underwent abdominoperineal resection and those with T4 tumors at
      presentation, the rate increases to 93%. The rate of recurrence anteriorly (7%)
      does not justify routine radiation of the anterior pelvis beyond that required to
      adequately cover the anastomotic site.

PMID- 12504047
TI  - Phase I trial of strictly time-scheduled gemcitabine and cisplatin with
      concurrent radiotherapy in patients with locally advanced pancreatic cancer.
AB  - PURPOSE: Maximal therapeutic gain in xenograft sarcoma and toxicity for jejunal
      mucosa is time dependent for concurrent gemcitabine and radiotherapy (RT). We
      used a time-dependent schedule to determine the maximal-tolerated dose and dose
      limiting toxicities (DLTs; Grade 4 hematologic or Grade 3 other toxicity).
      METHODS AND MATERIALS: Patients with pancreatic cancer (n = 33), periampullary
      carcinoma (n = 1), or bile duct cancer (n = 2) were treated with 3-day conformal
      RT with 50.4 Gy (tumor, lymphatics) plus a 5.4-Gy boost. Concurrent cisplatin (20
      mg/m(2)/d on Days 1-5 and 29-33) and gemcitabine (initially 600 mg/m(2), weekly
      on Fridays 68 h before RT) were administered. Because of DLT, the doses were
      reduced to 500 mg/m(2) weekly and then 500, 400, or 300 mg/m(2) on Days 2, 5, 26,
      33. RESULTS: DLT occurred at all dose levels of gemcitabine >300 mg/m(2).
      Fourteen patients were treated at the recommended Phase II dose of gemcitabine
      (300 mg/m(2)) without DLT. The response to chemoradiation allowed 10 of 30
      initially unresectable patients with primary pancreatic carcinoma to undergo
      radical surgery, including a complete response in 2 cases. CONCLUSIONS: At the
      recommended Phase II dose, chemoradiation with gemcitabine and cisplatin can be
      administered safely in pancreatic carcinoma. However, at higher dose levels,
      toxicity is severe and frequent. Patients with a chance for conversion to
      resection could benefit from this schedule.

PMID- 12504048
TI  - Prospective comparison of breast pain in patients participating in a randomized
      trial of breast-conserving surgery and tamoxifen with or without radiotherapy.
AB  - PURPOSE: To determine whether breast pain affects quality of life (QOL) after
      breast-conserving surgery and tamoxifen (TAM) with or without adjuvant breast
      radiotherapy (RT). METHODS AND MATERIALS: A randomized clinical trial was carried
      out at the Princess Margaret Hospital between 1992 and 2000 to evaluate the need
      for breast RT in addition to TAM in women >or=50 years treated with breast
      conserving surgery for T1-T2N0 breast cancer. A companion study to assess breast
      pain was carried out during the last 2 years of the randomized clinical trial.
      The short-form McGill Pain Questionnaire (SF-MPQ), the European Organization for
      Research and Treatment of Cancer (EORTC) QOL (QLQ-C30) and EORTC breast cancer
      module (QLQ-BR23) questionnaires were completed by patients within 1 week of
      randomization in the randomized clinical trial (baseline) and at 3, 6, and 12
      months. RESULTS: Eighty-six patients participated in the breast pain study; 41
      received RT plus TAM and 45 received TAM alone. The median age was 70 years
      (range 51-80). The baseline pain and QOL scores were similar for the two groups.
      No significant difference was found between the two groups for each scale of the
      QLQ-C30 and QLQ-BR23 questionnaires at 3, 6, or 12 months (p >0.100), except that
      at 12 months, the score for role function (QLQ-C30) was higher in the RT plus TAM
      group than in the RT-only group (p = 0.02). At 3 months, the difference between
      the mean scores for the SF-MPQ was 0.553 (p = 0.47). At 12 months, the pain
      scores had decreased in both groups; the difference was 0.199 (p = 0.71). The
      number of breast operations or surgical complications did not correlate with
      breast pain in either group. Acute RT toxicity scores did not correlate with
      breast pain or QOL scores at 12 months. CONCLUSION: These results suggest that
      breast RT does not significantly contribute to breast pain or adversely impact
      the QOL up to 12 months after treatment in postmenopausal patients with node
      negative breast cancer who take TAM.

PMID- 12504049
TI  - Clinical results of retreatment of vertebral bone metastases by stereotactic
      conformal radiotherapy and intensity-modulated radiotherapy.
AB  - PURPOSE: Reirradiation of spinal tumors is limited by the tolerance of the spinal
      cord. We evaluated local control, pain relief, neurologic improvement, side
      effects, and survival rates after fractionated conformal radiotherapy (FCRT) and
      intensity-modulated RT (IMRT) of recurrent spinal metastases. METHODS AND
      MATERIALS: Eighteen patients with 19 radiologic manifestations were retreated for
      recurrent spinal metastases using FCRT (n = 5) or IMRT (n = 14). All patients had
      previously undergone conventional RT (median dose 38 Gy). The indication for
      reirradiation was tumor progression associated with pain (n = 16) or neurologic
      symptoms (n = 12). The median time to recurrence was 17.7 months. The median
      total dose for reirradiation was 39.6 Gy. RESULTS: The overall local control rate
      was 94.7% after a median follow-up of 12.3 months. Of 16 patients with pain, 13
      experienced significant relief after reirradiation. Neurologic improvement was
      obtained in 5 of 12 patients. Tumor size remained unchanged in 84.2%. A partial
      response was seen in 2 of 19 patients. One patient had local tumor progression
      9.5 months after reirradiation. Six patients received chemotherapy after
      reirradiation because of progressive distant metastases. Twelve patients died
      10.5 months median after reirradiation. No clinically significant late toxicity
      was seen after FCRT or IMRT. CONCLUSION: These data demonstrate that FCRT and
      IMRT are effective and safe in recurrent spinal tumors and can be offered to
      patients to achieve local control, as well as pain relief.

PMID- 12504051
TI  - Is there a dose-effect relationship for the treatment of symptomatic vertebral
      hemangioma?
AB  - PURPOSE: Symptomatic vertebral hemangiomas are rare vascular lesions.
      Radiotherapy is the most common treatment. Because of a lack of information in
      the literature, uncertainty exists about the total radiation dose to be applied.
      METHODS AND MATERIALS: Individual data from our own and published patients with
      symptomatic vertebral hemangioma treated with radiotherapy alone were obtained.
      The data were pooled, and the impact of the total dose on complete pain relief
      was evaluated using the chi-square test. Because different single-fraction doses
      were used, the equivalent dose in 2-Gy fractions (EQD(2)) was used for the
      analysis. RESULTS: Complete data could be obtained from 117 patients. Patients
      were categorized according to total dose (EQD(2)) into two groups of similar size
      (Group A: 20-34 Gy, n = 62; and Group B: 36-44 Gy, n = 55). Radiation-induced
      complete pain relief was achieved in 39% (24/62) of the patients in Group A and
      in 82% (45/55) of the patients in Group B. The difference was statistically
      significant (p = 0.003). CONCLUSIONS: The data suggest a dose-effect relationship
      in the radiotherapy of symptomatic vertebral hemangiomas. We recommend a total
      radiation dose 36-40 Gy with a dose per fraction of 2.0 Gy.

PMID- 12504050
TI  - Local therapy in localized Ewing tumors: results of 1058 patients treated in the
      CESS 81, CESS 86, and EICESS 92 trials.
AB  - PURPOSE: The impact of different local therapy approaches on local control, event
      free survival, and secondary malignancies in the CESS 81, CESS 86, and EICESS 92
      trials was investigated. METHODS AND MATERIALS: The data of 1058 patients with
      localized Ewing tumors were analyzed. Wherever feasible, a surgical local therapy
      approach was used. In patients with a poor histologic response or with
      intralesional and marginal resections, this was to be followed by radiotherapy
      (RT). In EICESS 92, preoperative RT was introduced for patients with expected
      close resection margins. Definitive RT was used in cases in which surgical
      resection seemed impossible. In CESS 81, vincristine, adriamycin,
      cyclophosphamide, and actinomycin D was used. In CESS 86, vincristine,
      adriamycin, ifosfamide, and actinomycin D was introduced for patients with
      central tumors or primaries >100 cm(3). In CESS 92, etoposide, vincristine,
      adriamycin, ifosfamide, and actinomycin D was randomized against vincristine,
      adriamycin, ifosfamide, and actinomycin D in patients with primaries >100 cm(3).
      RESULTS: The rate of local failure was 7.5% after surgery with or without
      postoperative RT, and was 5.3% after preoperative and 26.3% after definitive RT
      (p = 0.001). Event-free survival was reduced after definitive RT (p = 0.0001).
      Irradiated patients represented a negatively selected population with unfavorable
      tumor sites. Definitive RT showed comparable local control to that of
      postoperative RT after intralesional resections. Patients with postoperative RT
      had improved local control after intralesional resections and in tumors with wide
      resection and poor histologic response compared with patients receiving surgery
      alone. Patients with marginal resections with or without postoperative
      radiotherapy showed comparable local control, yet the number of patients with
      good histologic response was higher in the latter treatment group (72.2% vs.
      38.5%). CONCLUSION: Patients with resectable tumors after initial chemotherapy
      had a low local failure rate. With preoperative RT, local control was comparable.
      RT is indicated to avoid intralesional resections. After intralesional or
      marginal resections and after a poor histologic response and wide resection,
      postoperative RT may improve local control.

PMID- 12504052
TI  - Retrobulbar irradiation for thyroid-associated orbitopathy: double-blind
      comparison between 2.4 and 16 Gy.
AB  - PURPOSE: Retrobulbar irradiation is used as a standard therapy for thyroid
      associated orbitopathy. The evidence of its effectiveness is, however, scarce.
      Doses from 2.5 to 20 Gy have been recommended. METHODS: Forty-three patients with
      active thyroid-associated orbitopathy were irradiated with 2.4 Gy and 43 with 16
      Gy. Five measures of outcome were used: (1) appearance of the eye region,
      documented with photographs; (2) Hertel exophthalmometry; (3) range of vertical
      eye movements; (4) eye muscle thickness (sum of three MRI sections across the
      eight rectus eye muscles); and (5) complaints, indicated on a visual analog
      scale. RESULTS: At 3 and 6 months after irradiation, no difference between 2.4
      and 16 Gy was found in any of the five outcome measures (p between 0.099 and
      0.993; Kruskal-Wallis test, Holm correction). Most outcome measures were
      slightly, but not significantly, improved in both the 2.4 and the 16 Gy groups.
      Patient complaints had improved significantly in both groups and the eye muscle
      thickness was significantly reduced in the 2.4 Gy group after 6 months.
      CONCLUSION: The lack of a difference between 2.4 and 16 Gy is compatible with
      four different interpretations: (1) the irradiation could be ineffective; (2) the
      maximal effect could be already reached at 2.4 Gy; (3) the maximal effect could
      lie between 2.4 and 16 Gy; and (4) the effect could increase beyond a threshold
      of >or=16 Gy. From general experience with inflammatory disease, the last two
      possibilities are unlikely; only the first two interpretations carry some
      probability. Although the design of the study did not allow a distinction between
      these two possibilities, we conclude that retrobulbar irradiation for thyroid
      associated orbitopathy should not exceed 2.4 Gy.

PMID- 12504053
TI  - Successful treatment of radiation nephropathy with angiotensin II blockade.
AB  - PURPOSE: The aim of this report is to document the successful treatment of
      radiation nephropathy. METHODS: Clinical case report with statistical analysis of
      evolution of kidney function. RESULTS: A case of radiation nephropathy was found
      in a kidney transplant recipient whose kidney transplant had been irradiated with
      750 cGy 23 years previously. Use of the angiotensin II blocker, losartan, was
      associated with significant stabilization of the kidney function. CONCLUSION:
      Radiation nephropathy can be successfully treated. Other normal-tissue radiation
      injuries may also be treatable.

PMID- 12504054
TI  - How low is the alpha/beta ratio for prostate cancer?
AB  - PURPOSE: It has been suggested recently that the alpha/beta ratio for human
      prostate cancer is low (around 1.5 Gy), and much debate on the evidence for such
      a low value is ongoing. Analyses reported so far ignored the contribution of
      tumor repopulation. Extremely low alpha values and unrealistic cell numbers of
      tumor clonogens are found in these studies. In this paper, we present a
      comprehensive analysis of the updated clinical data to derive a self-consistent
      set of parameters for the linear-quadratic (LQ) model. METHODS AND MATERIALS: The
      generalized LQ model, considering the effects of dose rate, sublethal damage
      repair, and clonogenic proliferation, was used to analyze the recently reported
      clinical data for prostate cancer using either external-beam radiotherapy or
      brachytherapy. Three LQ parameters, alpha, alpha/beta, and the repair time, were
      determined based on the clinical finding that the external-beam radiotherapy and
      the 125I and (103)Pd permanent implants are biologically equivalent. The tumor
      control probability model was used also to analyze the clinical data to obtain an
      independent relationship of alpha/beta vs. alpha and to estimate clonogenic cell
      numbers for patients in different risk groups. RESULTS: Based on the analysis of
      clinical data and a consideration of repopulation effect, we have derived a self
      consistent set of LQ parameters for prostate cancer: alpha = 0.15 +/- 0.04 Gy(
      1), alpha/beta = 3.1 +/- 0.5 Gy. Our analysis indicates the half-time of
      sublethal damage repair to be in the range from 0 to 90 min with a best estimate
      of 16 min. The best estimate of clonogenic cell numbers in prostate tumors is
      found to range from 10(6) to 10(7) according to the patient risk level. These
      values are more realistic than those derived previously (only 10-100).
      CONCLUSION: The effect of tumor repopulation is not negligible in determining the
      LQ parameters for prostate cancer, especially for the low-dose-rate permanent
      implants. Analysis of clinical data for prostate cancer with corrections for
      damage repair and repopulation effects results in a low alpha/beta ratio of 3.1
      Gy. Unrealistic clonogenic cell numbers and extremely small values of alpha
      reported in the literature can be resolved by correcting for repopulation effect.
      The LQ parameters derived presently from the clinical data are consistent with
      reports of intrinsic radiosensitivity in vitro.

PMID- 12504055
TI  - Dosimetric and technical considerations for interstitial adenoviral gene therapy
      as applied to prostate cancer.
AB  - PURPOSE: To introduce a simple and specific dosimetric model and an adenoviral
      delivery technique for interstitial adenoviral gene therapy of prostate cancer.
      METHODS AND MATERIALS: CG7060, a PSA-specific, replication-competent adenovirus,
      was used in a Phase I study in the treatment of 20 patients with locally
      recurrent prostate cancer. The virus was delivered directly into the prostate via
      transperineal needles under real-time transrectal ultrasonography guidance. Up to
      80 aliquots of 0.1-mL viral solution were injected into the prostate. The
      injection pattern, effective treatment volume (V(eff)), and viral dose
      distribution were determined according to a simple dosimetric model in which the
      local dose of virus was defined as the concentration of the delivered virion
      uniformly distributed in a sphere of 5-mm radius per injection. The initial
      dosimetric parameters were measured through scans of contrast solutions in dog
      prostate glands. The biochemical response (the reduction of serum PSA) as a
      function of the viral dose and tumor volume coverage was analyzed. RESULTS: A 0.1
      mL solution injected into the dog prostate gland spreads via 4-mm mechanical flow
      plus 1-mm molecular diffusion. Multiple injections into the prostate of patients
      resulted in considerable enlargement of the prostate gland. The biochemical
      response probability for patients treated with CG7060 may be estimated by 1 -
      alpha * exp[-[beta + gamma (PTV/V(eff)) P/A] * P], where alpha, beta, and gamma
      are constants; A is the number of aliquots, and P is the integral dose of initial
      viruses. CONCLUSION: A simple dosimetric model based on results from our recently
      reported Phase I study can quantify the biochemical response of patients treated
      with CG7060 adenoviral therapy. The model predicts that outcome is influenced by
      the integral dose of delivered virus and the target volume coverage. This first
      dosimetric model for interstitial adenoviral therapy will serve as a basis for
      quantitative analysis for ongoing and future studies.

PMID- 12504056
TI  - Beam orientation selection for intensity-modulated radiation therapy based on
      target equivalent uniform dose maximization.
AB  - PURPOSE: To develop an automated beam-orientation selection procedure for
      intensity-modulated radiotherapy (IMRT), and to determine if a small number of
      beams picked by this automated procedure can yield results comparable to a large
      number of manually placed orientations. METHODS AND MATERIALS: The automated beam
      selection procedure maximizes an unconstrained objective function composed of
      target equivalent uniform dose (EUD) and critical structure dose-volume histogram
      (DVH) constraints. Beam orientations are selected from a large feasible set of
      directions through a series of alternating fluence optimization and orientation
      alteration steps, until convergence to a stable orientation set. The fluence
      optimization step adjusts fluences to maximize the objective function. The
      orientation alteration step substitutes beams in the orientation set currently
      under consideration with beams of the parent set in the immediate angular
      vicinity; the altered orientation set is deemed current if it produces a higher
      objective function value in the fluence optimization step. RESULTS AND
      CONCLUSIONS: It is demonstrated, for prostate IMRT planning, that a modest number
      of appropriately selected beam orientations (3 or 5) can provide dose
      distributions as satisfactory as those produced by a large number of unselected
      equispaced orientations. Such selected beam orientations can reduce overall
      treatment time, thus making IMRT more clinically practical.

PMID- 12504057
TI  - MRI definition of target volumes using fuzzy logic method for three-dimensional
      conformal radiation therapy.
AB  - PURPOSE: Three-dimensional (3D) volume determination is one of the most important
      problems in conformal radiation therapy. Techniques of volume determination from
      tomographic medical imaging are usually based on two-dimensional (2D) contour
      definition with the result dependent on the segmentation method used, as well as
      on the user's manual procedure. The goal of this work is to describe and evaluate
      a new method that reduces the inaccuracies generally observed in the 2D contour
      definition and 3D volume reconstruction process. METHODS AND MATERIALS: This new
      method has been developed by integrating the fuzziness in the 3D volume
      definition. It first defines semiautomatically a minimal 2D contour on each slice
      that definitely contains the volume and a maximal 2D contour that definitely does
      not contain the volume. The fuzziness region in between is processed using
      possibility functions in possibility theory. A volume of voxels, including the
      membership degree to the target volume, is then created on each slice axis,
      taking into account the slice position and slice profile. A resulting fuzzy
      volume is obtained after data fusion between multiorientation slices. Different
      studies have been designed to evaluate and compare this new method of target
      volume reconstruction and a classical reconstruction method. First, target
      definition accuracy and robustness were studied on phantom targets. Second, intra
      and interobserver variations were studied on radiosurgery clinical cases.
      RESULTS: The absolute volume errors are less than or equal to 1.5% for phantom
      volumes calculated by the fuzzy logic method, whereas the values obtained with
      the classical method are much larger than the actual volumes (absolute volume
      errors up to 72%). With increasing MRI slice thickness (1 mm to 8 mm), the
      phantom volumes calculated by the classical method are increasing exponentially
      with a maximum absolute error up to 300%. In contrast, the absolute volume errors
      are less than 12% for phantom volumes calculated by the fuzzy logic method. On
      radiosurgery clinical cases, target volumes defined by the fuzzy logic method are
      about half of the size of volumes defined by the classical method. Also, intra-
      and interobserver variations slightly decrease with the fuzzy logic method,
      resulting in the definition of a better common volume fraction. CONCLUSION: Our
      fuzzy logic method shows accurate, robust, and reproducible results on phantoms
      and clinical targets imaged on MRI.

PMID- 12504058
TI  - Is there a preferred strength for regularly spaced 125I seeds in inverse-planned
      prostate implants?
AB  - PURPOSE: To determine whether a preferred seed strength exists for 125I prostate
      implants preplanned using a fixed intraneedle seed spacing of 1 cm and an
      objective needle placement strategy within the planning target volume (PTV), and
      incorporating explicit dose-volume constraints for the PTV and tissues at risk.
      METHODS AND MATERIALS: Prostate, urethra, and rectum contours for 10 patients
      were obtained from transrectal ultrasound studies. The PTV was defined in
      accordance with Radiation Therapy Oncology Group (RTOG) 0019 protocol. Inverse
      planning software was used to optimally arrange seeds of strength 0.3-0.8 U to
      cover the PTV to D(Rx) = 145 Gy, and limit urethra and rectum doses to 150% and
      100% of D(Rx), respectively. Isodose distributions and dosimetric indices were
      calculated: V(200), V(150), V(100), V(90), D(100), D(90) for PTV; V(150) for
      urethra; and V(100) for rectum. For seeds of strength 0.414 and 0.6 U and three
      prostate sizes, the sensitivity of V(90) and D(90) to elementary perturbations of
      the optimal seed arrangement were examined. RESULTS: For our planning scenario,
      125I seeds of strength 0.5-0.6 U provided the best possible PTV coverage while
      maintaining V(200) at approximately 25%. The source arrangement for 0.6-U seeds
      was only modestly more sensitive to perturbations than that for 0.414-U seeds.
      These findings may not be applicable to implants planned manually or that involve
      needle placement outside the PTV. CONCLUSION: Given a particular source
      arrangement, inverse planning aimed at maximizing dosimetric coverage of the
      prostate while limiting doses to the urethra and rectum can be used to search for
      a preferred seed strength. For regularly spaced sources within the PTV, higher
      strength seeds can provide better dose coverage and better urethral protection
      than lower strength seeds.

PMID- 12504059
TI  - Current calibration, treatment, and treatment planning techniques among
      institutions participating in the Children's Oncology Group.
AB  - PURPOSE: To report current technology implementation, radiation therapy physics
      and treatment planning practices, and results of treatment planning exercises
      among 261 institutions belonging to the Children's Oncology Group (COG). METHODS
      AND MATERIALS: The Radiation Therapy Committee of the newly formed COG mandated
      that each institution demonstrate basic physics and treatment planning abilities
      by satisfactorily completing a questionnaire and four treatment planning
      exercises designed by the Quality Assurance Review Center. The planning cases are
      (1) a maxillary sinus target volume (for two-dimensional planning), (2) a
      Hodgkin's disease mantle field (for irregular-field and off-axis dose
      calculations), (3) a central axis blocked case, and (4) a craniospinal
      irradiation case. The questionnaire and treatment plans were submitted (as of
      1/30/02) by 243 institutions and completed satisfactorily by 233. Data from this
      questionnaire and analyses of the treatment plans with monitor unit calculations
      are presented. RESULTS: Of the 243 clinics responding, 54% use multileaf
      collimators routinely, 94% use asymmetric jaws routinely, and 13% use dynamic
      wedges. Nearly all institutions calibrate their linear accelerators following
      American Association of Physicists in Medicine protocols, currently 16% with TG
      51 and 81% with TG-21 protocol. Treatment planning systems are relied on very
      heavily for all calculations, including monitor units. Techniques and results of
      each of the treatment planning exercises are presented. CONCLUSIONS: Together,
      these data provide a unique compilation of current (2001) radiation therapy
      practices in institutions treating pediatric patients. Overall, the COG
      facilities have the equipment and the personnel to perform high-quality radiation
      therapy. With ongoing quality assurance review, radiation therapy compliance with
      COG protocols should be high.

PMID- 12504060
TI  - Optimal stochastic correction strategies for rigid-body target motion.
AB  - PURPOSE: To derive optimal correction strategies for setup errors, including the
      uncertainty in their measurement, and to analyze their impact on treatment
      margins. METHODS AND MATERIALS: New concepts like image-guided radiotherapy aim
      to provide an increasing amount of targeting information during treatment. Future
      treatment devices incorporating imaging capabilities will facilitate frequent
      correction of treatment setup errors. It is, therefore, possible to design new
      correction protocols that reduce not only systematic but also random setup
      errors. A novel, very general approach to developing optimal correction
      strategies in the presence of measurement uncertainties is derived from linear
      systems theory. In the simplest approach, the state variable of the system, which
      represents the patient, is the spatial displacement of the center-of-mass of the
      clinical target volume with respect to the planning CT. This displacement is the
      sum of a systematic and a random component. Uncertainties in the measured value
      of the state variable due to the measurement process, image processing technique,
      or organ deformation are naturally incorporated into a linear system. The true
      value of the displacement can be estimated from the noisy measurements with a
      stochastic filter (Kalman filter). These estimates provide an optimal control law
      for the system and therefore optimal values for the setup corrections. In the
      case of unknown systematic and random error variances, an adaptive version of the
      filter was implemented. The statistical properties of the filter were
      investigated by performing simulations of the state space model and assessed for
      individual patients and a large patient population subject to different action
      criteria. RESULTS: Over a patient population, the corrections by the Kalman
      filter estimates are always advantageous compared with the corrections by the
      measured values themselves. For a small percentage of individual patients,
      however, the Kalman corrections worsen the results. For large measurement error,
      the residual standard deviation of the random setup errors can be reduced by
      approximately 28% for over 90% of the patients. The uncertainty in the measured
      value impairs the ability to completely account for uncertainties. CONCLUSIONS:
      The Kalman estimates provide an effective means to perform daily setup
      corrections in the presence of measurement errors. The linear system approach is
      very versatile and can be extended to more general state variables.

PMID- 12504061
TI  - Three-dimensional distribution of radiation within the breast: an intercomparison
      of departments participating in the START trial of breast radiotherapy
      fractionation.
AB  - PURPOSE: To examine the ability of computer planning systems to calculate the
      dose to the breast correctly in three dimensions. Both the absolute dose at the
      center of the breast and the accuracy of the isodose distributions were
      investigated. METHODS AND MATERIALS: Measurements were performed in a water
      filled breast phantom using an ionization chamber. Thirty-six sets of data
      obtained during the Standardization of Breast Radiotherapy breast fractionation
      trial quality assurance program were included in the analysis. The planning
      systems were grouped according to the algorithms used on the basis of the
      definitions given in International Commission on Radiation Units and Measurements
      Report No. 24. RESULTS: Thirty-two of the 36 planning systems overestimated the
      dose to the center of the breast, with a mean measured/calculated dose ratio of
      0.979 (SD 0.013). The relative dose within 2 cm of the lung was also
      overestimated. CONCLUSION: Only one algorithm (collapsed cone) investigated in
      this study was able to calculate the dose at the center of the breast correctly
      in tangential breast radiotherapy. With modern algorithms, it is important to
      include a correction for the lower density of the lung, because the dose close to
      the interface between breast and lung tissue will also be lower than anticipated.

PMID- 12504062
TI  - Registration of symptomatic patients with extramedullary hemopoiesis masses,
      treated by radiotherapy.

PMID- 12504064
TI  - Let's accelerate the PET learning curve.

PMID- 12504066
TI  - In response to Drs. Schild, Wong, and Nisi, IJROBP 2002;53:787.

PMID- 12504068
TI  - The second-generation 'atypical' antipsychotics: similar improved efficacy but
      different neuroendocrine side effects.
AB  - The neuroendocrine aspects of schizophrenia generally receive little attention.
      This is in marked contrast to depressive disorders, where neuroendocrine issues
      are central to discussions of pathophysiology and treatment. Although the nature
      of neuroendocrine dysfunction is less well characterized in schizophrenia than in
      major depression, a number of neuroendocrine abnormalities have been described.
      Hypercortisolemia has been extensively documented in patients with schizophrenia,
      particularly during acute exacerbations, with persistent hypercortisolemia being
      associated with ventricular enlargement and poor outcome. Similarly,
      abnormalities in thyroid function, the hypothalamo-pituitary-gonadal axis, growth
      hormone, prolactin, neurotensin, and other neuroendocrine parameters have also
      been described in schizophrenia. While the precise neuroendocrine profile of
      schizophrenia is incompletely characterized, the impact of antipsychotic
      medications employed in its treatment on various endocrine parameters is better
      understood. Different conventional and atypical antipsychotics variably
      contribute to hyperprolactinemia, insulin resistance, and other abnormalities. A
      critical overview of neuroendocrine abnormalities in schizophrenia is provided
      and the differential impact of different antipsychotics in contributing to
      neuroendocrine dysfunction is discussed.

PMID- 12504069
TI  - Efficacy of newer generation antipsychotics in the treatment of schizophrenia.
AB  - The advent of the newer 'atypical' antipsychotic medications has revolutionized
      the pharmacologic treatment of schizophrenia and other psychotic disorders. In
      contrast to the older conventional antipsychotic agents, atypical medications
      have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and
      mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive
      dyskinesia. Due to concerns surrounding hematological safety and other adverse
      effects, clozapine is used principally in patients refractory to treatment with
      other antipsychotic agents. The other three universally available atypical agents
      (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of
      all antipsychotic prescriptions in the USA. Despite the broad popularity of these
      medications and their rapid adoption in general clinical practice, there are
      limited data on how they compare to each other with regards to their overall
      efficacy and also as to their efficacy in specific symptom domains. To address
      this question, two separate analyses were undertaken. First, all published, short
      term, randomized, controlled clinical trials of these agents in schizophrenia and
      schizoaffective disorder were reviewed and the extent of improvement across these
      agents was compared. While the amount of improvement with a particular agent
      across its different studies varied, the average improvement was similar for the
      agents for all efficacy parameters considered. Secondly, all randomized,
      controlled clinical trials directly comparing two or more of these agents in
      patients with schizophrenia or schizoaffective disorder were analyzed. Only three
      such trials (all industry sponsored) were identified; while there were
      differences in methodology and small differences in efficacy on a minority of
      measures on which comparisons were undertaken, the preponderance of data
      suggested no differences in efficacy. While data thus far do not support
      assertions of differential efficacy between risperidone, olanzapine, and
      quetiapine, there are clear differences in their side-effect profiles and these
      are briefly summarized.

PMID- 12504070
TI  - Cognitive effects and antipsychotic treatment.
AB  - Cognitive impairment has long been recognized as central to the abnormalities
      that occur in schizophrenia, since neurocognitive deficits are predictive of a
      number of outcome indices, and they pose a significant obstacle to any attempts
      at social rehabilitation. This raises the possibility that treatments producing
      improvements in cognitive function might, in turn, prove to have synergistic
      effects with psychosocial interventions. Rather than improving cognitive
      deficits, conventional antipsychotics may instead contribute to the impairment
      seen in many patients with schizophrenia. These damaging effects on cognition
      might be expected not only when antipsychotic drugs with intrinsic
      anticholinergic properties are used but also when anticholinergic drugs are
      prescribed for the relief of treatment-emergent extrapyramidal symptoms. The
      atypical antipsychotic drugs may be effective in this area, either in
      amelioration of the cognitive impairments that occur in schizophrenia or in
      arresting any continuing decline. New-generation atypical agents, such as
      quetiapine and risperidone, have minimal intrinsic anticholinergic effects, which
      suggest that some of the additional negative effects on cognition can be avoided.
      A number of large-scale, long-term follow-up studies of atypical antipsychotics
      are currently underway, in 'real world' settings, to assess not only control of
      symptoms of schizophrenia but also improvement in social, occupational, and inter
      personal functioning.

PMID- 12504071
TI  - Atypical antipsychotics in the EPS-vulnerable patient.
AB  - 'Typical' antipsychotic agents can lead to a variety of extrapyramidal symptoms
      (EPS), including parkinsonism. The efficacy of a number of atypical
      antipsychotics in reducing psychosis without a detrimental effect on motor
      function has been studied in the group of patients most vulnerable to EPS, those
      who already have parkinsonian symptoms. Multiple open-label studies with
      clozapine strongly suggested that at low doses the drug was an effective
      antipsychotic and did not impair motor function. This was confirmed by two double
      blind, placebo-controlled studies. A disadvantage of clozapine is that it can
      cause agranulocytosis and therefore patients require ongoing hematological
      monitoring. Studies with both risperidone and olanzapine have produced
      conflicting results, with some patients showing an overall improvement and others
      exhibiting severe deterioration of motor function. As with clozapine, multiple
      open-label studies with quetiapine have consistently demonstrated that it
      improves psychosis without impairing motor function. Double-blind trials are yet
      to be performed: however, the existing data, coupled with the lack of required
      blood monitoring, have led some experts to recommend quetiapine as the drug of
      choice for treatment of drug-induced psychosis in patients with parkinsonism. The
      atypical antipsychotics have also been tested in the largest group of EPS
      vulnerable patients, the demented elderly. Results from a number of trials are
      described here. These data are more difficult to interpret as the number of
      variables is far greater than for the population with parkinsonism. However, the
      evidence to date indicates a generally low incidence of tardive dyskinesia with
      atypical antipsychotics.

PMID- 12504072
TI  - Elevated prolactin levels in patients with schizophrenia: mechanisms and related
      adverse effects.
AB  - The neurologic processes involved in schizophrenia are complex and diverse and
      the mechanisms through which antipsychotic agents exert their effects have been
      only partly elucidated. Hyperprolactinemia is a common side effect of treatment
      with many antipsychotics and is particularly associated with conventional
      ('typical') agents as well as the atypical antipsychotic risperidone. In
      contrast, other atypical agents introduced over the last decade do not elevate
      prolactin levels. This article discusses the regulatory mechanisms involved in
      prolactin secretion, the physiologic role of prolactin, and the etiology of
      hyperprolactinemia. Elevated prolactin levels may play important roles, both
      direct and indirect, in various pathologic states, including breast cancer,
      osteoporosis, cardiovascular disorders, and sexual disturbances. Antipsychotic
      induced hyperprolactinemia may be associated with similar clinical
      manifestations; these are examined with particular reference to patients with
      schizophrenia.

PMID- 12504073
TI  - Sexual dysfunction and antipsychotic treatment.
AB  - Human sexual function is complex and affected in many different ways by
      schizophrenia and the antipsychotic drugs used in its treatment. The evaluation
      of the effects of antipsychotics on sexual function in patients with
      schizophrenia is also complex because the deleterious effects of conventional
      antipsychotics are superimposed on the effects of the disease itself. Although
      not extensively researched, sexual dysfunction seems to be frequent in patients
      with schizophrenia, especially in men. Sexual dysfunction appears, in significant
      part, to be a direct consequence of dopamine antagonism, combined with indirect
      effects due to increased serum prolactin concentration. Atypical antipsychotics
      have a number of potential advantages over standard agents with regard to their
      impact on sexual function. Clinical reports indicate that atypical antipsychotics
      are associated with a lower incidence of sexual adverse events than conventional
      antipsychotics and that there may also be important differences between them in
      this regard. For example, dose-related increases in prolactin concentrations
      occur with risperidone whereas olanzapine is associated with mild and transient
      increases in long-term treatment. Treatment with clozapine does not result in
      prolactin elevation and, like olanzapine, only transient increases occur with
      ziprasidone therapy, but the risk of agranulocytosis with clozapine restricts its
      use. Quetiapine has no more effect on serum prolactin than placebo across its
      full dose range. Together with its low frequency of reproductive or hormonal side
      effects and a low incidence of extrapyramidal symptoms, the tolerability profile
      of quetiapine may be particularly beneficial for many patients. Sexual
      dysfunction can be an important source of distress to patients and adversely
      affects compliance, and is one of the factors that must be taken into account
      when selecting treatment.

PMID- 12504074
TI  - A review of the effect of atypical antipsychotics on weight.
AB  - Controlled research trials have shown that atypical antipsychotics have important
      advantages over standard antipsychotics, including a broader spectrum of efficacy
      and improved tolerability profile, particularly with regard to neurological
      adverse events such as extrapyramidal symptoms (EPS). Some atypical
      antipsychotics, however, tend to cause significant weight gain, which may lead to
      poor compliance and other adverse health effects. The mechanisms involved in
      antipsychotic drug-related weight gain are as yet uncertain, although
      serotoninergic, histaminic, and adrenergic affinities have been implicated along
      with other metabolic mechanisms. The atypical antipsychotics vary in their
      propensity to cause weight change with long-term treatment. Follow-up studies
      show that the largest weight gains are associated with clozapine and olanzapine,
      and the smallest with quetiapine and ziprasidone. Risperidone is associated with
      modest weight changes that are not dose related. Given the equivalent efficacy of
      atypical antipsychotics, weight-gain profile is a legitimate factor to consider
      when constructing an algorithm for treatment due to the serious medical
      consequences of obesity.

PMID- 12504075
TI  - Expression of leptin receptors and response to leptin stimulation of human
      natural killer cell lines.
AB  - We previously reported that deficiency of leptin receptor (Ob-R(-/-), db/db) in
      mice led to impaired NK cell function. In the present paper, we, for the first
      time, found that human NK cell lines constitutively expressed leptin receptor (Ob
      R), both long form Ob-R (Ob-R(L)) and short form Ob-R (Ob-R(S)), using
      immunohistochemical method, Western blotting, and RT-PCR assay. Interestingly, IL
      2-dependent NK-92 cells proliferated without change in the presence or absence of
      leptin stimulation, but their cytotoxicity was dose-dependently responsible for
      leptin stimulation. The IL-2-independent YT cells were dose-dependently
      responsible for leptin stimulation to manifest rapid proliferation and strong
      cytotoxicity against tumor targets. In order to explain the mechanisms underlying
      the leptin function on NK cell lines, we examined the gene expression of
      cytokines (IL-2, IFNr), cytotoxic-associated molecules (perforin, FasL) and the
      activation of cytokine signal pathways (STAT1, STAT3). The results demonstrated
      that leptin activated the phosphorylation of STAT3 and then improved
      transcription of IL-2 and perforin genes. Our preliminary study indicates that
      leptin could affect NK cell function and may play an important role in innate
      immunity.

PMID- 12504076
TI  - Hexamerization of p97-VCP is promoted by ATP binding to the D1 domain and
      required for ATPase and biological activities.
AB  - The 97-kDa valosin-containing protein (p97-VCP or VCP), a hexameric AAA ATPase,
      plays an important role in diverse cell activities, including ubiquitin
      proteasome mediated protein degradation. In this report, we studied dissociation
      reassembly kinetics to analyze the structure-function relationship in VCP. Urea
      dissociated VCP can reassemble by itself, but addition of ATP, ADP, or ATP-gamma
      S accelerates the reassembly. Mutation in the ATP-binding site of D1, but not D2,
      domain abolishes the ATP acceleration effect and further delays the reassembly.
      Using hybrid hexamers of the wild type and ATP-binding site mutant, we show that
      hexameric structure and proper communication among the subunits are required for
      the ATPase activity and ubiquitin-proteasome mediated degradation. Thus, ATP
      binding site in D1 plays a major role in VCP hexamerization, of which proper
      inter-subunit interaction is essential for the activities.

PMID- 12504077
TI  - Reduction of protein-tyrosine phosphatase-1B increases insulin signaling in FAO
      hepatoma cells.
AB  - Protein-tyrosine phosphatase-1B (PTP1B) has been implicated as a negative
      regulator of insulin signaling. PTP1B dephosphorylates the insulin receptor and
      insulin receptor substrates (IRS-1/2), inhibiting the insulin-signaling pathway.
      PTP1B has been reported to be elevated in diabetes and insulin-resistant states.
      Conversely, PTP1B null mice have increased insulin sensitivity. To further
      investigate the effect of PTP1B reduction on insulin signaling, FAO rat hepatoma
      cells were transfected, by electroporation, with a specific PTP1B antisense
      oligonucleotide (ASO), or a control oligonucleotide. The PTP1B ASO caused a 50
      70% reduction in PTP1B protein expression as measured by Western blot analysis.
      Upon insulin stimulation, an increase in the phosphorylation of the insulin
      receptor and insulin receptor substrates was observed, without any change in
      protein expression levels. Reduction of PTP1B expression in FAO cells also caused
      an increase in insulin-stimulated phosphorylation of PKB and GSK3, without any
      change in protein expression. These results demonstrate that reduction of PTP1B
      can modulate key insulin signaling events downstream of the insulin receptor.

PMID- 12504078
TI  - Identification of the RT-RH/IN cleavage site of HTLV-I.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is a type C human retrovirus and is
      the causative agent of adult T-cell leukemia and other diseases. The enzymatic
      and structural proteins of HTLV-I are synthesized as part of a Gag-Pro-Pol
      precursor polyprotein, and the mature proteins are released by proteolytic
      processing catalyzed by HTLV-I protease. The locations of most of the proteolytic
      cleavage sites are known, however, the site that creates the N-terminus of HTLV-1
      integrase has not been previously identified. A 15 residue peptide corresponding
      to junction of the C-terminus of RNaseH and N-terminus of integrase
      (DALLITPVLQLSPAF-OH) was incubated with HTLV-1 protease. Analysis of the cleavage
      products by LC-MS revealed fragments Ac-DALLITPVLQL-OH and H(2)N-SPAF-OH were
      produced, indicating cleavage between the leucine and serine. This is the first
      physical identification of the N-terminal amino acid sequence of the integrase of
      HTLV-1.

PMID- 12504079
TI  - Structures of cadmium-binding acidic phospholipase A2 from the venom of
      Agkistrodon halys Pallas at 1.9A resolution.
AB  - Phospholipase A(2) coordinates Ca(2+) ion through three carbonyl oxygen atoms of
      residues 28, 30, and 32, two carboxyl oxygen atoms of residue Asp49, and two (or
      one) water molecules, forming seven (or six) coordinate geometry of Ca(2+)
      ligands. Two crystal structures of cadmium-binding acidic phospholipase A(2) from
      the venom of Agkistrodon halys Pallas (i.e., Agkistrodon blomhoffii brevicaudus)
      at different pH values (5.9 and 7.4) were determined to 1.9A resolution by the
      isomorphous difference Fourier method. The well-refined structures revealed that
      a Cd(2+) ion occupied the position expected for a Ca(2+) ion, and that the
      substitution of Cd(2+) for Ca(2+) resulted in detectable changes in the metal
      binding region: one of the carboxyl oxygen atoms from residue Asp49 was farther
      from the metal ion while the other one was closer and there were no water
      molecules coordinating to the metal ion. Thus the Cd(2+)-binding region appears
      to have four coordinating oxygen ligands. The cadmium binding to the enzyme
      induced no other significant conformational change in the enzyme molecule
      elsewhere. The mechanism for divalent cadmium cation to support substrate binding
      but not catalysis is discussed.

PMID- 12504080
TI  - Pregnane X receptor-dependent and -independent effects of 2-acetylaminofluorene
      on cytochrome P450 3A23 expression and liver cell proliferation.
AB  - The arylamide 2-acetylaminofluorene (AAF) is a powerful carcinogen displaying a
      marked promoting activity, also known to regulate expression of liver detoxifying
      proteins. In this study we identified CYP3A23, a major inducible cytochrome P-450
      (CYP) isoform, as an AAF target in hepatocytes. Indeed, exposure to AAF of
      primary rat hepatocytes resulted in a marked up-regulation of CYP3A23 expression
      at both mRNA and protein levels. Using CYP3A23 reporter gene constructs, we
      further demonstrated that AAF activated the CYP3A23 Direct Repeat 3 (DR3)
      promoter element interacting with the nuclear pregnane X receptor (PXR).
      Moreover, the PXR antagonist ecteinascidin-743 fully suppressed AAF-related
      CYP3A23 induction. Low doses of AAF inhibiting DNA synthesis in hepatocytes
      however failed to trigger PXR-related CYP3A23 induction and PXR-negative
      epithelial liver cells remained sensitive to the mito-inhibitory effects of AAF.
      Such data indicate that AAF up-regulates CYP3A23 through PXR activation but does
      not require PXR for exerting its carcinogenic promoting properties based on
      inhibition of cell growth.

PMID- 12504081
TI  - Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin.
AB  - We previously characterized a peanut agglutinin-binding tumor antigen, gp200, a
      surface membrane glycoprotein expressed on human embryonal carcinoma, a malignant
      stem cell of testicular tumors. Gp200 is remarkably similar to another embryonal
      carcinoma antigen, GCTM-2, a cell differentiation marker that is also detected in
      blood of testis cancer patients, yet neither molecular identity is known. We now
      report the identity of gp200 as podocalyxin. Protein sequence results of gp200
      peptides match with podocalyxin sequence. Furthermore, two distinct monoclonal
      antibodies, specific for podocalyxin, react positively with gp200. Therefore,
      gp200 is a testicular tumor form of podocalyxin, a surface membrane glycoprotein
      that was originally discovered as a scaffolding extracellular matrix protein of
      kidney podocyte cells. Podocalyxin is also expressed on subsets of hematopoietic
      cells where it has a putative function as a cell adhesion protein. This is the
      first report of podocalyxin expression on malignant cells.

PMID- 12504082
TI  - Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma
      chain.
AB  - Interleukin 21 (IL-21) is a recently identified novel cytokine that plays an
      important role in the regulation of B, T, and NK cell functions. Its effects
      depend on binding to and signaling through an IL-21 receptor complex consisting
      of the IL-21 receptor (IL-21R) and the common gamma-chain (gamma(c)). In this
      study using biosensor technique, the ligand-binding properties of IL-21R and
      gamma(c), which are presently poorly understood on a molecular level, were
      analyzed employing recombinant ectodomains of IL-21R and gamma(c). The formation
      of a binary complex between IL-21 and immobilized IL-21R (K(D) 70pM), gamma(c)
      and immobilized IL-21 (K(D) 160 microM) and a ternary complex between gamma(c)
      and IL-21 saturated immobilized IL-21R (K(D) 160nM) could be analyzed. The
      gamma(c) residues involved in IL-21 binding were defined by alanine-scanning
      mutational analysis. The epitope comprises gamma(c) residues N44, Y103, N128,
      L161, E162, and L208. It is not identical but partially overlapping with the
      previously established gamma(c) epitope for IL-4 binding. These results open the
      way to understand the molecular recognition mechanism in the IL-21 receptor
      system and also the promiscuous binding properties of gamma(c).

PMID- 12504083
TI  - Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2a.
AB  - UFD2a is a mammalian homolog of Saccharomyces cerevisiae Ufd2, originally
      described as an E4 ubiquitination factor. UFD2a belongs to the U-box family of
      ubiquitin ligases (E3s) and likely functions as both an E3 and E4. We have
      isolated and characterized the mouse gene (Ube4b) for UFD2a. A full-length
      (approximately 5700 bp) Ube4b cDNA was isolated and the corresponding gene spans
      >100 kb, comprising 27 exons. Luciferase reporter gene analysis of the 5(')
      flanking region of Ube4b revealed that nucleotides -1018 to -943 (relative to the
      translation initiation site) possess promoter activity. This functional sequence
      contains two putative Sp1 binding sites but not a TATA box. Immunoblot and
      immunohistochemical analyses revealed that UFD2a is expressed predominantly in
      the neuronal tissues. We also show that UFD2a interacts with VCP (a AAA-family
      ATPase) that is thought to mediate protein folding. These data implicate UFD2a in
      the degradation of neuronal proteins by the ubiquitin-proteasome pathway.

PMID- 12504084
TI  - Disordered calcium crystal handling in antisense CLC-5-treated collecting duct
      cells.
AB  - Dent's disease, an X-linked tubulopathy secondary to defects in chloride channel
      CLC-5, is characterised by low molecular weight proteinuria, hypercalciuria,
      nephrocalcinosis, and renal stones. Mechanisms leading to nephrocalcinosis are
      unknown. Using a murine collecting duct cell line (mIMCD-3), we confirm
      endogenous expression of mCLC-5. During transfection of antisense CLC-5, we
      observe a reduction in CLC-5 protein expression that correlates with a reduction
      in the number of acidic endosomal compartments, as determined by quantitative
      analysis of confocal microscope images using LysoTracker Red. Using wheat germ
      agglutinin-lectin as an endocytic marker, an arrest of endocytosis is observed in
      antisense CLC-5 treated cells. Exposure of the cell surface to calcium oxalate
      crystals results in crystal agglomeration in a minority of sense CLC-5
      transfectants (45%) and all antisense CLC-5 transfectants. We conclude that
      expression of CLC-5 in mIMCD-3 cells allows acidification of endosomes and
      endocytosis, and that disruption of CLC-5 expression causes abnormal crystal
      agglomeration.

PMID- 12504085
TI  - RAGE-mediated MAPK activation by food-derived AGE and non-AGE products.
AB  - Investigating the cellular effects of food compounds formed by heat treatment
      during processing, we recently demonstrated the expression of the receptor for
      advanced glycation endproducts (RAGE) and the p44/42 MAP kinase activation by
      casein-N(epsilon )-(carboxymethyl)lysine (casein-CML), a food-derived AGE, in the
      intestinal cell line Caco-2. In this work, we report a Caco-2 p44/42 MAP kinase
      activation by bread crust and coffee extract. After identification,
      quantification, and synthesis of two key compounds formed in association with the
      process-induced heat impact applied to bread dough and coffee beans, those
      compounds, namely the AGE pronyl-glycine and the non-AGE N-methylpyridinium, were
      also demonstrated for the first time to activate the p44/42 MAP kinase through
      binding to RAGE in Caco-2 cells. Blocking of RAGE by an antagonistic antibody and
      expression of C-terminally truncated RAGE resulted in a reduced Caco-2- and HEK
      293-MAP kinase activation. These findings unequivocally point to a RAGE-mediated
      activating effect of chemically defined food-derived, thermally generated
      products, both, AGEs and non-AGEs, on cellular signal transduction pathways
      involved in inflammatory response and cellular proliferation.

PMID- 12504086
TI  - Effects of sterculic acid on stearoyl-CoA desaturase in differentiating 3T3-L1
      adipocytes.
AB  - The effects of sterculic acid on cell size, adiposity, and fatty acid composition
      of differentiating 3T3-L1 adipocytes are correlated with stearoyl-CoA desaturase
      (SCD) expression (mRNA and protein levels) and enzyme activity. Fluorescence
      activated cell scanning (FACS) analysis showed that adipocytes differentiated
      with methylisobutylxanthine, dexamethasone, and insulin (MDI) plus 100 microM
      sterculic acid comprised a population of predominantly large cells with reduced
      adiposity compared to MDI-treated cells. Although both groups had similar amounts
      of total fat, their fatty acid profiles were strikingly different: MDI-treated
      cells had high levels of the unsaturated palmitoleic (Delta(9)-16:1) and oleic
      (Delta(9)-18:1) acids, whereas the cells cultured with MDI plus sterculic acid
      accumulated palmitic (16:0) and stearic (18:0) acids together with a marked
      reduction in Delta(9)-16:1. Although the cells treated with MDI plus sterculic
      acid had similar levels of scd1 and scd2 mRNAs and antibody-detectable SCD
      protein as the MDI-treated cells, the SCD enzyme activity was inhibited more than
      90%. The accumulation of 16:0 and 18:0, together with normal levels of fatty acid
      synthase (FAS) and aP2 mRNAs, shows that de novo synthesis and elongation of
      fatty acids, as well as cell differentiation, were not affected by sterculic
      acid. Because of the increase in cell size in the sterculic acid-treated cells,
      the insulin-stimulated 2-deoxyglucose (2-DOG) uptake was determined. Compared to
      MDI-treated cells, the 2-DOG uptake in the cells treated with sterculic acid was
      not affected. These results indicate that sterculic acid directly inhibits SCD
      activity, possibly by a turnover-dependent reaction, without affecting the
      processes required for adipocyte differentiation, scd gene expression or SCD
      protein translation.

PMID- 12504087
TI  - Down-regulation of topoisomerase II alpha is caused by up-regulation of GRP78.
AB  - Glucose-regulated protein of M(r) 78kDa (GRP78) is a resident protein of
      endoplasmic reticulum (ER). We have previously shown that the cells become
      resistant to topoisomerase II alpha (topo II alpha) targeted cancer
      chemotherapeutic drug such as etoposide (VP-16) when GRP78 is up-regulated by
      various means. Up-regulation of GRP78 in V79 Chinese hamster cell lines was
      achieved by treating the cells with NAD antagonist 6-aminonicotinamide (6AN),
      inhibitor of glucose metabolism such as 2-deoxyglucose (2dG). Further, up
      regulation of GRP78 was also observed in V79-derived cell lines which are
      deficient in poly(ADP-ribose) polymerase (PARP1) metabolism. However, mechanisms
      of association of GRP78 up-regulation and resistance to VP-16 remained obscured
      under the conditions outlined above. In the manuscript, using various methods, we
      demonstrate, for the first time, that up-regulation of GRP78, using approaches
      depicted above, causes down-regulation of topo II alpha and its activity. We have
      also discussed the clinical implications of our findings.

PMID- 12504088
TI  - Organic anion and cation transporters occur in pairs of similar and similarly
      expressed genes.
AB  - Organic anion and cation transporters (OATs, OCTs, OCTNs, and ORCTLs),
      transmembrane proteins essential to renal xenobiotic excretion, are encoded by a
      group of related genes. As yet there have been no studies of the transcriptional
      regulation of this important gene family. While such studies have traditionally
      been labor-intensive, comparative genomics approaches are now available that have
      proven reliable guides to critical regulatory elements. We report here the
      genomic sequencing of murine OAT1 (the cDNA of which was originally cloned by us
      as NKT) and OAT3 (Roct), and derivation of phylogenetic footprints
      (evolutionarily conserved non-coding sequences) by comparison to the human
      genome. We find binding sites within these footprints for several transcription
      factors implicated in kidney development, including PAX1, PBX, WT1, and HNF1.
      Additionally, we note that OATs and OCTs occur in the human and mouse genomes as
      tightly linked pairs (OAT1 and OAT3, UST3 and OAT5, OAT4 and URAT1/RST, OCT1 and
      2, OCTN1 and 2, ORCTL3 and 4) that are also close phylogenetic relations, with
      Flipt1 and 2, and OAT2 the only unpaired family members. Finally, we find that
      pair-members have similar tissue distributions, suggesting that the pairing might
      exist to facilitate the co-regulation of the genes within each pair.

PMID- 12504089
TI  - Cloning of human and rat ABCA5/Abca5 and detection of a human splice variant.
AB  - We presently report the cloning of cDNA sequences encoding the novel rat ATP
      binding cassette (ABC) transporter Abca5 and the orthologous human transporter,
      recently designated as ABCA5. Furthermore, the existence of a novel non
      translated exon of the ABCA5 gene, previously assigned to an ABCA gene cluster in
      the chromosomal region 17q24.2-3, is demonstrated. Abca5 and ABCA5 cDNAs are
      predicted to give rise to proteins of 1642 amino acids which exhibit the typical
      domain arrangement of ABC full transporters and share 90% identity within the
      amino acid sequences. A cDNA representing an ABCA5 mRNA splice variant was cloned
      which would result in a truncated protein equivalent to an ABC half transporter.
      Northern blot analyses revealed expression of ABCA5 or Abca5 mRNA in several
      tissues, but particularly high Abca5 mRNA expression was observed in rat testis.
      Up-regulation of Abca5 mRNA expression during culture of primary rat hepatocytes
      suggests that hepatocyte cultures should provide a basis for investigation of
      Abca5 gene regulation and elucidation of Abca5 function.

PMID- 12504090
TI  - A 35-kDa co-aggregation factor is a hemin binding protein in Porphyromonas
      gingivalis.
AB  - It has been known that Porphyromonas gingivalis has an obligate requirement for
      hemin or selected heme- or Fe-containing compounds for its growth. In addition,
      the influence of hemin on the expression of several putative virulence factors
      produced by this bacterium has also been recently documented; however, the
      mechanisms involved in hemin uptake are poorly defined. We succeeded in cloning
      the gene coding for the 35-kDa protein, which was specifically expressed in P.
      gingivalis and seemed to confer colonizing activities. Recently, we have
      constructed the P. gingivalis 381 mutant defective in the 35-kDa protein by
      insertion mutagenesis. The beige mutant exhibited little co-aggregation and the
      virulence was also decreased. Based on these results and homology search
      analysis, we focused on assessing the hemin bindings and found the heme
      regulatory motif (HRM) as a hemin direct binding site. The 35-kDa protein did
      possess the binding ability of selected protoporphyrins involving the hemin.
      These results demonstrated that 35-kDa protein is one of the hemin binding
      proteins in P. gingivalis and suggested that hemin binding ability of 35-kDa
      protein is important for the expression of virulence in P. gingivalis.

PMID- 12504091
TI  - Vitamin E succinate inhibits human prostate cancer cell growth via modulating
      cell cycle regulatory machinery.
AB  - Several epidemiological studies have demonstrated that vitamin E is a
      chemopreventative agent for prostate cancer. alpha-Tocopheryl succinate (VES), a
      derivative of vitamin E, effectively modulates prostate cancer cell growth.
      However, little is known about the mechanisms regarding this action. Here we show
      that VES causes human prostate cancer cell LNCaP arrest at G1 phase. This effect
      is accomplished through VES significantly decreasing expression of the cell cycle
      regulatory proteins cyclin D1, D3, and E, cdk2 and 4, but not cdk6. Furthermore,
      VES reduces cdk4 kinase activity, Rb phosphorylation, and cyclin E mRNA
      expression. Recently there is increasing interest in the protective effect of the
      VES and selenium combination on prostate cancer. Here we show that VES and
      selenium work through different mechanisms to exert their inhibitory effects on
      prostate cancer cells. Taken together, our studies suggest that VES-mediated
      prostate cancer cell G1/S arrest is a consequence of the regulation of multiple
      molecules of the cell cycle regulatory machinery.

PMID- 12504092
TI  - Filtrin is a novel member of nephrin-like proteins.
AB  - NPHS1 encodes nephrin, the core protein of the interpodocyte slit diaphragm of
      the kidney glomerulus. NPHS1 is the causative gene for congenital nephrotic
      syndrome of the Finnish type (CNF) with massive, treatment resistant proteinuria.
      We report here the establishment of a novel nephrin-like gene, NLG1 encoding
      filtrin, a protein with substantial homology to human nephrin. Filtrin is a type
      I transmembrane protein consisting of 708 amino acids. Together with the recently
      cloned NEPH1, NLG1 establishes a new nephrin-like subgroup of genes belonging to
      the immunoglobulin superfamily of cell adhesion molecules. The RNA dot blot
      experiment revealed that the NLG1 mRNA expression is widely distributed but most
      prominently observed in the pancreas and lymph nodes. The expression of NLG1 mRNA
      in kidney glomeruli was verified with RT-PCR. Further immunoblotting studies with
      antifiltrin antibody showed a specific band at 107kDa in the human and rat
      glomeruli. In immunofluorescence microscopy specific staining of glomeruli but
      also proximal and distal parts of the nephron was seen in human kidney cortex.
      Due to its structural similarity and sequence homology as well as partially
      consistent expression pattern with nephrin we propose that filtrin belongs to a
      functionally important complex of proteins of the glomerular filtration barrier.

PMID- 12504093
TI  - Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis.
AB  - In primary adipocytes, insulin receptor substrate (IRS)-1 and -3 are expressed in
      a comparable amount and play distinct roles in insulin signaling. To examine the
      roles of these IRS in apoptosis inhibition, we evaluated staurosporine-induced
      apoptosis in Chinese hamster ovary (CHO) cells overexpressing human insulin
      receptor and IRS-1 or IRS-3. Overexpression of both IRS protected CHO cells from
      staurosporine-induced apoptosis. Overexpressed IRS-3 as well as IRS-1 enhanced
      phosphoinositide (PI) 3-kinase activity in response to insulin and increased
      phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of
      the members of the forkhead transcription factor FKHRL1 on T32 in both insulin
      untreated and -treated states. Treatment of these cells with a PI 3-kinase
      inhibitor LY294002 suppressed apoptosis-inhibitory effects of IRS-1 and IRS-3 as
      well as the phosphorylation of PKB and FKHRL1. These results indicate that both
      IRS-1 and IRS-3 take part in apoptosis inhibition through the PI 3
      kinase/PKB/forkhead cascade.

PMID- 12504094
TI  - A methionine sulfoxide reductase in Escherichia coli that reduces the R
      enantiomer of methionine sulfoxide.
AB  - It is known that Escherichia coli methionine mutants can grow on both enantiomers
      of methionine sulfoxide (met(o)), i.e., met-R-(o) or met-S-(o), indicating the
      presence of enzymes in E. coli that can reduce each of these enantiomers to
      methionine (met). Previous studies have identified two members of the methionine
      sulfoxide reductase (Msr) family of enzymes, MsrA and fSMsr, that could reduce
      free met-S-(o), but the reduction of free met-R-(o) to met has not been
      elucidated. One possible candidate is MsrB which is known to reduce met-R-(o) in
      proteins to met. However, free met-R-(o) is a very poor substrate for MsrB and
      the level of MsrB activity in E. coli extracts is very low. A new member of the
      Msr family (fRMsr) has been identified in E. coli extracts that reduces free met
      R-(o) to met. Partial purification of FRMsr has been obtained using extracts from
      an MsrA/MsrB double mutant of E. coli.

PMID- 12504095
TI  - Reconstitution of Smad3 restores TGF-beta response of tissue inhibitor of
      metalloprotease-1 upregulation in human choriocarcinoma cells.
AB  - Extravillous trophoblast (EVT) cells of the human placenta proliferate, migrate,
      and invade the pregnant uterus and its vasculature in order to nourish the fetus.
      However, the normal EVT cell proliferation, migration, and invasiveness are
      exquisitely controlled in situ by decidua-produced transforming growth factor
      beta (TGF-beta), whereas EVT cancer (choriocarcinoma) cells are TGF-beta
      resistant. We found that these cells lack in expression of Smad3, a key
      transcription factor involved in TGF-beta signaling pathway. To test whether
      Smad3 restitution restores TGF-beta response in choriocarcinoma cells, we
      produced a Smad3-expressing cell line (JAR-smad3/c). Since anti-invasive effect
      of TGF-beta in the normal EVT cells was partly mediated by an upregulation of
      tissue inhibitor of metalloprotease (TIMP)-1, we examined whether Smad3
      restituted JAR cells have restored TGF-beta response of TIMP-1 upregulation. The
      expression of TIMP-1 mRNA was found to be low in JAR and JAR-smad3/c cells.
      Moreover, the basal level of secreted TIMP-1 protein was very low in these cells
      as compared to the normal EVT cells. TGF-beta1 upregulated TIMP-1 mRNA and
      secreted protein in Smad3-restituted JAR cells as well as in the normal EVT
      cells, whereas no effect was detected in Smad3-deficient (wild-type) JAR cells.
      We had earlier shown that Smad3-restituted JAR cells had also restored TGF-beta
      response of plasminogen activator inhibitor-1 upregulation. However, in vitro
      functional analysis revealed that, in contrast to the normal EVT cells, anti
      invasive action of TGF-beta was not restored in Smad3-restituted JAR cells. Thus,
      additional factors (possibly low expression of Smad4 and/or other unknown
      factors) may contribute to refractoriness to anti-invasive action of TGF-beta in
      JAR cells.

PMID- 12504096
TI  - Point mutations in BCL6 DNA-binding domain reveal distinct roles for the six zinc
      fingers.
AB  - The B-cell lymphoma 6 (BCL6) gene encodes a transcriptional repressor containing
      six C-terminal Kruppel-like zinc fingers. The zinc finger (ZF) cluster is
      necessary and sufficient for interaction with both DNA and several proteins and
      for nuclear targeting. However, the functional specificity of the six ZFs in
      these cellular roles is unknown. To characterize this domain, we mutated
      individually each ZF of BCL6. Our results reveal that mutation of the two N
      terminal ZFs does not impair cognate DNA-binding, cellular localization of the
      protein nor the transcriptional repression capacity of BCL6. By contrast,
      mutation of any of the remaining ZFs abolishes the binding of BCL6 to DNA in
      vitro and the transrepressive function of the protein in vivo. Finally, none of
      the six mutations affect the interaction between BCL6 and class II histone
      deacetylases. Thus our experiments demonstrate that BCL6 uses each of the four C
      terminus ZFs for binding to a target sequence while the two amino terminal
      fingers are likely engaged in other unknown function(s).

PMID- 12504097
TI  - HMGCoA reductase inhibition partially mediates tumor necrosis factor alpha
      induced apoptosis in human U-937 and HL-60 cells.
AB  - We have examined the effects of tumor necrosis factor alpha (TNF alpha) and its
      second messenger, ceramide, on HMGCoA reductase, the rate-limiting enzyme in the
      mevalonate pathway. Treatment of human U-937 and HL-60 cells with TNF alpha or C2
      ceramide inhibited both expression and activity of HMGCoA reductase in a time
      dependent manner. Maturation of p21(ras) was also inhibited in a mevalonate
      dependent fashion. The addition of mevalonate to both U-937 and HL-60 cells could
      also partially prevent TNF alpha and ceramide-induced apoptosis. These results
      support the hypothesis that the inhibition of HMGCoA reductase expression and the
      subsequent decrease in prenylation of proteins such as p21(ras) are part of the
      mechanism by which TNF alpha induces apoptosis in these cells.

PMID- 12504098
TI  - An intracellular targeted NLS peptide inhibitor of karyopherin alpha:NF-kappa B
      interactions.
AB  - The nuclear import of transcription factors involves proteins termed
      karyopherins. Previously, we described an intracellular targeted dual nuclear
      localization sequence (NLS) peptide inhibitor of processes dependent upon the
      transcription factor NF-kappa B. We have now developed a homogeneous solution
      based assay and show that NF-kappa B interacts with karyopherin alpha and that
      the dual NLS peptide inhibits this interaction. We also show that both L- and D
      amino acid containing peptides bind well to karyopherin alpha 2, whereas, the L
      amino acid peptides bind more efficiently than the D-amino acid peptide to
      karyopherin alpha1.

PMID- 12504099
TI  - Scorpion toxins that block T-type Ca2+ channels in spermatogenic cells inhibit
      the sperm acrosome reaction.
AB  - The acrosome reaction (AR) is a Ca(2+)-dependent event required for sperm to
      fertilize the egg. The activation of T-type voltage-gated Ca(2+) channels plays a
      key role in the induction of this process. This report describes the actions of
      two toxins from the scorpion Parabuthus granulatus named kurtoxin-like I and II
      (KLI and KLII, respectively) on sperm Ca(2+) channels. Both toxins decrease T
      type Ca(2+) channel activity in mouse spermatogenic cells and inhibit the AR in
      mature sperm. Saturating concentrations of the toxins inhibited at most
      approximately 70% of the whole-cell Ca(2+) current, suggesting the presence of a
      toxin-resistant component. In addition, both toxins inhibited approximately 60%
      of the AR, which is consistent with the participation of T-type Ca(2+) channels
      in the sperm AR.

PMID- 12504100
TI  - A CRE and the region occupied by a protein induced by growth factors contribute
      to up-regulation of cyclin D1 expression in hepatocytes.
AB  - Induction of cyclin D1 expression is a critical feature of growth factor-induced
      cell proliferation in hepatocytes. To clarify the mechanisms regulating cyclin D1
      gene expression, we isolated the rat cyclin D1 gene and analyzed the
      transcriptional regulatory elements in rat hepatoma cells and primary cultured
      rat hepatocytes. Two transcriptional regulatory regions were analyzed. One was
      mapped to a cAMP-responsive element (CRE) at position -41bp and was occupied by a
      CRE-binding protein (CREB), resulting in cyclin D1 expression. Another (CD1E0.7),
      located at -753bp, revealed high homology with binding sites for the Ets family,
      the hepatocyte nuclear factor-3beta, or the nuclear factor of activated T cells.
      However, CD1E0.7 did not interact with these nuclear factors and specific
      interaction with a protein extracted from growth factor-treated rat hepatocytes
      in primary cultures. These results indicate that CREB binds to the CRE and
      mediates activation of the cyclin D1 promoter, and suggest that CD1E0.7 may be
      possibly occupied by a protein induced by growth factors in hepatocytes.

PMID- 12504101
TI  - Mass spectrometric analysis of the perisympathetic organs in locusts:
      identification of novel periviscerokinins.
AB  - A mass spectrometric analysis carried out to determine the peptidome of the
      abdominal perisympathetic organs in the locust species Locusta migratoria and
      Schistocerca gregaria yielded a number of predominant ion peaks, among which are
      Lom-PVK (AAGLFQFPRVamide) and Scg-MT-2 (TSSLFPHPRLamide). In addition, three
      novel peptides were identified: Lom-PVK-2 (identical in Schistocerca):
      GLLAFPRVamide, Lom-PVK-3: DGGEPAAPLWFGPRVamide, and Scg-PVK-3:
      DGAETPGAAASLWFGPRVamide. An extensive mass spectrometric study of the central
      nervous system showed that the periviscerokinins (-PRVamides) and Scg-MT-2 (
      FXXPRLamide) are restricted to the abdominal ganglia and their perisympathetic
      organs, while the pyrokinins (-FXPRLamides) are present only in the brain
      retrocerebral complex. Sequence comparison with the Drosophila genes supports a
      conserved gene structure whereby a capability-like gene encodes the
      periviscerokinins that are expressed in the abdominal ganglia and stored in the
      perisympathetic organs, while a hugin-like gene encodes the pyrokinins that are
      expressed in the head ganglia and stored in the retrocerebral complex.

PMID- 12504102
TI  - Regulation of PPAR gamma transcriptional activity in 3T3-L1 adipocytes.
AB  - PPAR gamma is a member of the nuclear hormone receptor superfamily and functions
      as a transcriptional regulator of genes linked to adipogenesis and lipid
      metabolism. The regulation of PPAR gamma activity by insulin signaling molecules
      in adipocytes has yet to be clarified. Therefore, it is important to measure
      endogenous PPAR gamma transcriptional activities in response to various stimuli
      in adipocytes. Herein, with a transcription reporter assay using recombinant
      adenovirus vectors expressing PPRE (PPAR responsive elements)-reporter genes, we
      established a novel system for measuring endogenous PPAR gamma transcriptional
      activity in 3T3-L1 adipocytes. By means of this system, a marked increase (8.5
      fold) in PPAR gamma transcriptional activity was detected after treatment with
      10(-6)M pioglitazone, a thiazolidinedione (TZD), indicating that this system can
      measure PPAR gamma activity accurately. Furthermore, MAPK activation, achieved by
      overexpressing constitutively activated MEK1, inhibited PPAR gamma
      transcriptional activity. In contrast, treatment with PKA stimulators markedly
      increased PPAR gamma activity. Interestingly, PI 3-kinase overexpression resulted
      in a marked decrease in PPAR gamma activity. These observations have important
      implications for understanding the regulation of PPAR gamma transcriptional
      activity.

PMID- 12504103
TI  - Involvement of the Src kinase Lyn in phospholipase C-gamma 2 phosphorylation and
      phosphatidylinositol 3-kinase activation in Epo signalling.
AB  - We examined the role of the Src kinase Lyn in phospholipase C-gamma 2 (PLC-gamma
      2) and phosphatidylinositol (PI) 3-kinase activation in erythropoietin (Epo)
      stimulated FDC-P1 cells transfected with a wild type (WT) Epo-receptor (Epo-R).
      We showed that two inhibitors of Src kinases, PP1 and PP2, abolish both PLC-gamma
      2 tyrosine phosphorylation and PI 3-kinase activity in WT Epo-R FDC-P1 cells. We
      also demonstrated that Epo-phosphorylated Lyn is associated with tyrosine
      phosphorylated PLC-gamma 2 and PI 3-kinase in WT Epo-R FDC-P1-stimulated cells.
      Moreover Epo-activated Lyn phosphorylates in vitro PLC-gamma 2 immunoprecipitated
      from unstimulated cells. Our results suggest that the Src kinase Lyn is involved
      in PLC-gamma 2 phosphorylation and PI 3-kinase activation induced by Epo.

PMID- 12504104
TI  - Differential cellular gene expression induced by hepatitis B and C viruses.
AB  - Hepatitis B virus (HBV) is a hepatotropic virus that causes acute and chronic
      hepatocellular injury and hepatocellular carcinoma. To clarify how HBV proteins
      regulate host cellular gene expression, we used our in-house cDNA microarray and
      HepG2.2.15 cells, which are derived from HepG2 cells and produce all HBV
      proteins. Of 2304 genes investigated, several genes were differentially expressed
      in HepG2.2.15 cells compared with HepG2 cells. These genes included insulin-like
      growth factor II and alpha-fetoprotein, consistent with previous reports.
      Furthermore, we previously performed similar microarray analyses to clarify the
      effects of hepatitis C virus (HCV) proteins on host cells, using a HepG2
      derivative cell line, which produces all HCV proteins. Using these two microarray
      results, we compared the differences in cellular gene expression induced by HBV
      and HCV proteins. The expression of the majority of genes investigated differed
      only slightly between HBV and HCV protein-producing cells. However, HBV and HCV
      proteins clearly regulated several genes in a reciprocal manner. Combined, these
      microarray results shed new light on the effects of HBV proteins on cellular gene
      expression and on the differences in the pathogenic activities of these two
      hepatitis viruses.

PMID- 12504105
TI  - Spontaneous mutations in the human gene for p53 in recombinant adenovirus during
      multiple passages in human embryonic kidney 293 cells.
AB  - Infectious recombinant adenovirus (rAd) is usually produced in human embryonic
      kidney 293 cells that harbor the E1 gene and rAd has been shown to be an
      efficient tool for gene transfer both in vivo and in vitro. It also has
      considerable potential in human gene therapy. However, rates of spontaneous
      mutations in genes introduced into host cells after multiple passages remain to
      be clarified. We have characterized the spontaneous mutation of genomes derived
      from human adenovirus type 5 (Ad5) and of human p53-rAd during multiple passages
      by two different methods, namely, a plaque assay and a molecular cloning assay,
      with subsequent direct nucleotide sequencing. Using the plaque assay, we found no
      mutations in the E1A and p53 genes derived from infectious Ad5 and p53-rAd,
      respectively. By contrast, we found spontaneous mutations in the E1A gene of Ad5,
      with a mutation rate of 9.28 x 10(-8) per base pair per plaque, in the molecular
      cloning assay. The rate of mutation of the p53 gene of p53-rAd, as determined by
      the molecular cloning assay, ranged from 1.50 x 10(-7) to 3.25 x 10(-7) per base
      pair per passage. The mutations in the p53 gene of p53-rAd were localized mainly
      in the transcriptional activation domain, the SH3 domain, and the regulation
      domain and they were rarely found in the DNA-binding domain, which is a major
      site for mutations in human cancers. Our results indicate that multiple passages
      can generate a heterogeneous population of p53-rAd and that the molecular cloning
      assay is an efficient technique with which to search for mutations in the genome
      of p53-rAd that cannot be detected by a plaque assay.

PMID- 12504106
TI  - Depressed phosphatidic acid-induced contractile activity of failing
      cardiomyocytes.
AB  - The effects of phosphatidic acid (PA), a known inotropic agent, on Ca(2+)
      transients and contractile activity of cardiomyocytes in congestive heart failure
      (CHF) due to myocardial infarction were examined. In control cells, PA induced a
      significant increase (25%) in active cell shortening and Ca(2+) transients. The
      phospholipase C (PLC) inhibitor, 2-nitro-4-carboxyphenyl N,N-diphenylcarbonate,
      blocked the positive inotropic action induced by PA, indicating that PA induces
      an increase in contractile activity and Ca(2+) transients through stimulation of
      PLC. Conversely, in failing cardiomyocytes there was a loss of PA-induced
      increase in active cell shortening and Ca(2+) transients. PA did not alter
      resting cell length. Both diastolic and systolic [Ca(2+)] were significantly
      elevated in the failing cardiomyocytes. In vitro assessment of the cardiac
      sarcolemmal (SL) PLC activity revealed that the impaired failing cardiomyocyte
      response to PA was associated with a diminished stimulation of SL PLC activity by
      PA. Our results identify an important defect in the PA-PLC signaling pathway in
      failing cardiomyocytes, which may have significant implications for the depressed
      contractile function during CHF.

PMID- 12504107
TI  - HVJ-envelope vector for gene transfer into central nervous system.
AB  - To overcome some problems of virus vectors, we developed a novel non-viral vector
      system, the HVJ-envelope vector (HVJ-E). In this study, we investigated the
      feasibility of gene transfer into the CNS using the HVJ-E both in vitro and in
      vivo. Using the Venus reporter gene, fluorescence could be detected in cultured
      rat cerebral cortex neurons and glial cells. In vivo, the reporter gene (Venus)
      was successfully transfected into the rat brain by direct injection into the
      thalamus, intraventricular injection, or intrathecal injection, without inducing
      immunological change. When the vector was injected after transient occlusion of
      the middle cerebral artery, fluorescence due to EGFP gene or luciferase activity
      could be detected only in the injured hemisphere. Finally, luciferase activity
      was markedly enhanced by the addition of 50 U/ml heparin (P<0.01). Development of
      efficient HVJ-E for gene transfer into the CNS will be useful for research and
      clinical gene therapy.

PMID- 12504108
TI  - Resistin is expressed in human macrophages and directly regulated by PPAR gamma
      activators.
AB  - Resistin is a cysteine-rich protein postulated to be a molecular link between
      obesity and type 2 diabetes. The aim of this study was to investigate the role of
      PPAR gamma in the regulation of resistin expression in human primary macrophages.
      Fluorescent real-time PCR (Taqman) analysis of resistin expression across a range
      of human tissues showed that resistin is highly expressed in bone marrow compared
      to other tissues. Taqman analysis and Western blotting showed that rosiglitazone
      decreased resistin expression at both the mRNA and protein levels in human
      primary monocyte-derived macrophages in vitro. Resistin expression was reduced by
      up to 80% after exposure to 100 nM rosiglitazone for 96 h. Bioinformatics
      analysis of the genomic sequence upstream of the resistin coding sequence
      identified several putative PPAR response elements of which one was shown to bind
      PPAR gamma using electrophoretic mobility shift assays. Our data support a direct
      role for PPAR gamma in the regulation of resistin expression.

PMID- 12504109
TI  - In CCR2-/- mice monocyte recruitment and egress of LDL cholesterol in vivo is
      impaired.
AB  - Recruitment of macrophages plays an important role in initiation of atheroma, but
      their involvement in cholesterol clearance during regression is unknown. We
      developed a mouse model to quantitate cholesterol clearance from a depot of
      cationized LDL injected into a leg muscle, which evokes a sterile inflammatory
      reaction. In the CCR2(-/-) mice, cholesterol clearance was significantly slower
      than in C57BL controls because of decrease in cholesteryl ester (CE) hydrolysis,
      which is mandatory prior to cholesterol efflux. In CCR2(-/-) mice, macrophage
      recruitment to the injected site, identified by immunohistochemistry, was
      markedly delayed. CE hydrolysis was also significantly reduced in thioglycollate
      elicited peritoneal exudate cells of CCR2(-/-) mice, related to paucity of
      macrophages in the cell differential. The present study provides definite
      evidence that recruitment of macrophages is required for LDL cholesterol
      clearance, which plays a prominent role in regression of an atheroma.

PMID- 12504110
TI  - Differential sublocalization of the dynamin-related protein OPA1 isoforms in
      mitochondria.
AB  - OPA1 is a cause gene for autosomal dominant optic atrophy and possesses eight
      alternative splicing variants. Here, we identified two isoforms of OPA1 proteins
      in HeLa cells and examined their submitochondrial localization and complex
      formations. RT-PCR shows that HeLa cells mainly express isoforms 7 and 1 of OPA1.
      Since the third cleavage site is mainly utilized in HeLa cells, the predicted
      molecular masses of their processed proteins are consistent with the 93- and 88
      kDa proteins. Biochemical examinations indicate that both of the OPA1 isoforms
      are present in the intermembrane space. Submitochondrial fractionation by sucrose
      density-gradient centrifugation shows that the 88-kDa protein predominantly
      associates with the mitochondrial outer membrane, on the contrary, the 93-kDa
      protein associates with the inner membrane. Gel filtration analysis indicates
      that they compose the different molecular mass complexes in mitochondria. These
      differences between two isoforms of OPA1 would suggest their crucial role
      involved in the mitochondrial membrane formation.

PMID- 12504111
TI  - The c-Cbl-associated protein and c-Cbl are two new partners of the SH2-containing
      inositol polyphosphate 5-phosphatase SHIP2.
AB  - SHIP2 is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) 5
      phosphatase which contains motifs susceptible to mediate protein-protein
      interaction. Using yeast two-hybrid, GST-pulldown, and coimmunoprecipitation
      studies, we isolated the CAP cDNA as a specific partner of SHIP2 proline-rich
      domain and showed by GST-pulldown experiments that the interaction took place
      with the SH3C of CAP. The interaction was not modulated in COS-7 cells stimulated
      by EGF neither in CHO cells overexpressing the insulin receptor in the presence
      or absence of insulin stimulation. We also showed that SHIP2 was able to
      coimmunoprecipitate with endogenous c-Cbl protein in the absence of CAP and with
      the insulin receptor in CHO-IR cell extracts. The presence of SHIP2 in a complex
      around the insulin receptor could account for the very specific increase in
      insulin sensitivity of SHIP2 knock-out mice.

PMID- 12504112
TI  - The effect of high-density lipoproteins on the formation of lipid/protein
      conjugates during in vitro oxidation of low-density lipoprotein.
AB  - High-density lipoprotein (HDL) incubated with low-density lipoprotein (LDL) under
      oxidising conditions has previously been reported to decrease the accumulation of
      lipid peroxides on LDL and to diminish the biological effects of LDL, which would
      have been present had it been oxidatively modified in the absence of HDL. Thus
      far direct evidence that oxidative modification of LDL is diminished by HDL has,
      however, been lacking. We used electrospray ionisation mass spectrometry (ESI-MS)
      to detect 4-hydroxy-2-nonenal (HNE)-modified histidine residues of tryptic
      fragments of LDL which had been subject to Cu(2+) induced oxidation both in the
      presence and absence of human or avian HDL. HNE-modified angiotensin II was
      introduced into the incubation mixture as an internal standard and to check that
      HDL did not interfere in the detection of HNE-modified peptides non-specifically.
      Our results confirmed earlier reports that HNE modification of histidine occurs
      during the oxidation of LDL and for the first time revealed a marked attenuation
      of the process in the presence of human HDL with no effect on the detection of
      HNE-modified angiotensin II by ESI-MS. Avian HDL, which lacks the anti-oxidative
      enzyme paraoxonase, did not affect the formation of apo B adducts. Our findings
      therefore suggest that covalent linkage of lipid peroxidation products to LDL
      protein as well as the accumulation of lipid peroxides on LDL is diminished in
      the presence of HDL containing paraoxonase.

PMID- 12504113
TI  - Rapid and sensitive detection of avian influenza virus subtype H7 using NASBA.
AB  - Nucleic acid sequence-based amplification with electrochemiluminescent detection
      (NASBA/ECL) is an isothermal technique allowing rapid amplification and detection
      of specific regions of nucleic acid from a diverse range of sources. It is
      especially suitable for amplifying RNA. A NASBA/ECL technique has been developed
      allowing the detection of RNA from avian influenza virus subtype H7 derived from
      allantoic fluid harvested from inoculated chick embryos and from cell cultures.
      Degenerate amplification primers and amplicon capture probes were designed
      enabling the detection of low and highly pathogenic avian influenza of the H7
      subtype from the Eurasian and North American lineages and the Australian sub
      lineage. The NASBA/ECL technique is specific for subtype H7 and does not cross
      react with other influenza subtypes or with viruses containing haemagglutinin
      like genes. The assay is 10- to 100-fold more sensitive than a commercially
      available antigen capture immunoassay system. The NASBA/ECL assay could be used
      in high throughput poultry screening programmes.

PMID- 12504114
TI  - Specific modulation of the anti-DNA autoantibody-nucleic acids interaction by the
      high affinity RNA aptamer.
AB  - Anti-DNA autoantibodies are one of the frequently found autoantibodies in
      systemic lupus erythematosus patient sera. RNA aptamers for the monoclonal G6-9
      anti-DNA autoantibody were selected from a random pool of RNA library. Binding
      affinity of the best aptamer is around 2nM, which is at least 100-fold higher
      than that of cognate DNA antigen to the autoantibody. Aptamer binds specifically
      to the G6-9 autoantibody but not to other similar autoantibodies. Minimal binding
      motif of the aptamer was mapped, providing a hint for a natural epitope of the
      autoantibody. DNA binding to the G6-9 autoantibody is shown to be efficiently
      inhibited by the aptamer. Such binding property of the RNA aptamer could be used
      not only as a modulator for the pathogenic anti-DNA autoantibody, but also as a
      useful biochemical reagent for elucidating a fine specificity of the autoantibody
      nucleic acid interaction.

PMID- 12504115
TI  - Benzo(c)quinolizinium drugs inhibit degradation of Delta F508-CFTR cytoplasmic
      domain.
AB  - Proteins comprising the first nucleotide-binding- and R-domains of wild-type and
      Delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) have been
      synthesised by in vitro transcription/translation. The kinetics and extent of
      degradation of wild-type and Delta F508 cytoplasmic domain proteins in rabbit
      reticulocyte lysates, in which proteasome activity was inhibited, were similar,
      with a half-life of approximately 4h. The results show for the first time, that
      the benzo(c)quinolizinium compounds, MPB-07 and MPB-91, selectively inhibit
      degradation of the Delta F508 cytoplasmic domain protein. Studies using protease
      inhibitors demonstrated that both Delta F508 and wild-type proteins are
      substrates for cysteine proteases. The studies provide evidence that
      benzo(c)quinolizinium compounds protect a proteolytic cleavage site by direct
      binding to the first cytoplasmic domain of Delta F508-CFTR and this is a likely
      mechanism for increasing Delta F508-CFTR trafficking in intact cells.

PMID- 12504116
TI  - Human serum amyloid A3 peptide enhances intestinal MUC3 expression and inhibits
      EPEC adherence.
AB  - We previously determined that the N-terminal region of bovine mammary-associated
      serum amyloid A3 (M-SAA3) increased intestinal mucin MUC3 levels in HT29 human
      intestinal cells by approximately 2.5-fold, relative to untreated cells. This
      study shows that the human M-SAA3 N-terminal peptide further enhances MUC3
      transcript levels by approximately 4.3-fold in these cells (p<0.02), implicating
      a species-specific interaction. Furthermore, immunofluorescence and immunoblot
      analysis using a MUC3-specific monoclonal antibody confirms that the human M-SAA3
      peptide stimulates MUC3 protein expression and secretion by the HT29 cells. More
      importantly, pretreatment of the cells with the peptide causes a subsequent 73%
      decrease in the adherence of enteropathogenic Escherichia coli (EPEC) to these
      cells, relative to untreated cells (p<0.01). The intestinal mucin MUC3 has been
      shown to provide a protective barrier in the gut and inhibit adherence of
      pathogens to the gut wall. Therefore, a means to increase MUC3 protein expression
      by a colostrum-associated peptide or protein may be a highly effective
      prophylactic treatment for the prevention of gastrointestinal diseases such as
      necrotizing enterocolitis and infectious diarrhea.

PMID- 12504117
TI  - Dynamic and morphological investigation of phospholipid monolayer hydrolysis by
      phospholipase C.
AB  - The hydrolytic reaction of L-alpha-dipalmitoylphosphatidylcholine (L-DPPC)
      monolayer catalyzed by phospholipase C (PLC) has been investigated using
      monomolecular membrane technique and Brewster angle microscopy (BAM) at the
      air/water interface. The curves of surface pressure as a function of time
      determined a lag-burst process of L-DPPC monolayer hydrolysis by PLC. The BAM
      images recorded the changes of domains formed in the coexistence region of liquid
      condensed (LC) and liquid-expanded (LE) phases during the monolayer hydrolysis.
      The changes of domain shape and size and the increase of domain number reflect
      the decrease of reactant and molecular rearrangement process of the main
      hydrolysis product, dipalmitoylglycerol (DPG). A new phase was observed after the
      hydrolysis reaction was completed.

PMID- 12504118
TI  - Relationship between a HCO3- -permeable conductance and a CLCA protein from rat
      pancreatic zymogen granules.
AB  - Ca(2+)-induced enzyme secretion in the exocrine pancreas is not completely
      understood. We have proposed that Ca(2+)-induced enzyme secretion in the exocrine
      pancreas involves activation of ion conductances in the membrane of zymogen
      granules (ZG). Here we have identified a Ca(2+)-activated anion conductance in
      rat pancreatic ZG membranes (ZGM). Ca(2+) (2.5-50 microM) increased the
      conductance for I(-), NO(3)(-), Br(-), or HCO(3)(-), but not for Cl(-), as
      determined by the rate of valinomycin-induced osmotic lysis of ZG suspended in
      isotonic K(+)-salts. 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulfonate (100
      microM) or 25 microM dithiothreitol strongly inhibited Ca(2+)-dependent lysis.
      The permeability sequence, Ca(2+) dependence, and inhibitor sensitivity of ZG
      anion conductance are reminiscent of a family of epithelial Ca(2+)-activated
      anion channels (CLCA). CLCA expression was confirmed by RT-PCR with rat
      pancreatic mRNA and mouse CLCA1 primers. A PCR product (580bp) exhibited 81%,
      77%, and 57% amino acid similarity to the three mouse isoforms mCLCA-1, -2, and 
      3 (mgob-5), respectively. Antibodies against bovine tracheal CLCA1 showed CLCA
      expression in ZGM by immunoblotting, immunoperoxidase light microscopy, and
      immunogold labeling. These findings suggest that a CLCA-related protein could
      account for the Ca(2+)-activated HCO(3)(-) conductance of rat pancreatic ZGM and
      contribute to hormone-stimulated enzyme secretion.

PMID- 12504119
TI  - Interaction of a GATA factor with cis-acting elements involved in light
      regulation of nuclear genes encoding chloroplast glyceraldehyde-3-phosphate
      dehydrogenase in Arabidopsis.
AB  - We have previously identified a cis-acting element, named the XXIII box, that is
      essential for light-regulated expression of the nuclear gene GAPB, which encodes
      the B subunit of chloroplast glyceraldehyde-3-phosphate dehydrogenase from
      Arabidopsis thaliana. Examination of the sequences indicated that there are two
      GATA motifs within the XXIII box. Based on the degree of the amino-acid sequence
      identity in the DNA binding domains, we divided the 25 GATA factors encoded in
      the Arabidopsis genome into three classes. We chose GATA-1 and GATA-20 from Class
      I and Class II, which include the majority of GATA factors, for overexpression in
      an Escherichia coli expression system. Gel mobility shift assays showed that GATA
      1, but not GATA-20, binds specifically to the two GATA motifs within the XXIII
      fragment. In addition, we showed that GATA-1 could also bind specifically to a
      cis-acting element in the promoter of the GAPA gene, which is coordinately
      regulated by light with the GAPB gene. Based on these results, we propose that
      light controls the expression of GAPA and GAPB genes in part by regulating the
      binding of the same transcription factor at their GATA motifs.

PMID- 12504120
TI  - Molecular mechanisms of L-selectin-induced co-localization in rafts and shedding
      [corrected].
AB  - Leukocyte recruitment to lymph nodes or inflammatory sites is regulated by
      adhesion and activation. L-selectin (CD62L) is expressed on leukocytes and
      mediates tethering and rolling of leukocytes on endothelial cells. Upon
      stimulation L-selectin is down-regulated by proteolytic cleavage but the
      molecular mechanisms regulating this shedding step are poorly defined. To study
      intracellular mechanisms, we induced shedding of L-selectin by cross-linking with
      an immobilized L-selectin antibody (Dreg56) in Jurkat cells. The loss of surface
      expression was quantitated by flow cytometry and the increase of soluble L
      selectin was determined by Western blot analysis. We find that Jurkat and
      p56(lck)-deficient JCaM1.6 cells released L-selectin to similar extent (18+/-4%
      and 17+/-3%, respectively) and revealed comparable inhibition with the src
      tyrosine kinase inhibitor PP2. Glutathione (GSH), an inhibitor of the neutral
      sphingomyelinase, PD98059, a MAP-kinase (MAP-K) inhibitor and metalloprotease
      inhibitors (MPI) (TAPI, Ro 31-9790, and BB-3103) reduced significantly L-selectin
      induced shedding by 60-80%. In Jurkat cells, L-selectin was present in Triton X
      100 insoluble membrane rafts and was constitutively tyr-phosphorylated. Dreg56
      cross-linking enhanced phosphorylation and recruitment of L-selectin into rafts
      which was significantly decreased by pretreatment of cells with PD98059. We
      conclude, that the metalloproteinase-mediated cleavage of L-selectin from cell
      surface is triggered by intracellular signaling pathways that are independent of
      p56(lck) tyrosine kinase activity, but require other tyrosine kinases and the
      neutral sphingomyelinase. The cleavage of L-selectin might involve membrane rafts
      as signaling platform.

PMID- 12504121
TI  - Genomic structure, expression, and transcriptional regulation of human Gal beta
      1,3 GalNAc alpha 2,3-sialyltransferase gene.
AB  - In this report, we describe transcriptional regulation of the human Gal beta 1,3
      GalNAc alpha 2,3-sialyltransferase II (hST3Gal II) gene. The results of 5'-RACE
      showed that the forms of two mRNAs differed only in the 5'-untranslated region
      (Types 1 and 2). According to analysis of the genomic structure, the
      transcriptional regulation of Type 1 and Type 2 mRNA isoforms depended on the p1
      and p2 promoters, respectively. Both the mRNA isoforms were detected in various
      human tissues except colon, skeletal muscle, and peripheral blood leukocytes by
      RT-PCR analysis. In colon tissue, the Type 2 mRNA was detected, however, Type 1
      mRNA was not detected. To elucidate the molecular basis of hST3Gal II gene
      expression, we isolated and characterized the function of the genomic region of
      hST3Gal II containing the p1 and p2 promoters. The activity of p2 promoter is
      much higher than that of the p1 promoter in the colon adenocarcinoma cell line,
      COLO205. These results suggest that the hST3Gal II gene is expressed specifically
      by alternative promoter utilization and is regulated in a tissue-restricted
      fashion at the level of transcription.

PMID- 12504122
TI  - Transcriptional profiling of gene expression patterns during sphingosine 1
      phosphate-induced mesangial cell proliferation.
AB  - Sphingosine 1-phosphate (S1P) is known to regulate cell proliferation, apoptosis,
      and motility. Recently, we have reported that S1P and its analogue dihydro-S1P
      (DHS1P) promote proliferation of rat cultured mesangial cells. To investigate the
      signaling mechanisms underlying S1P- and DHS1P-induced mesangial cell
      proliferation, we performed cDNA microarray analysis of gene expression during
      mesangial cell proliferation. In terms of the overall pattern, gene expression
      waves induced by S1P and DHS1P were similar to those induced by a potent
      mesangial mitogen platelet-derived growth factor (PDGF), whereas we found several
      genes, such as two growth factors, connective tissue growth factor (CTGF) and
      heparin-binding EGF-like growth factor (HB-EGF), which were induced by the
      sphingolipids, but not by PDGF. Cluster analysis also identified calcium
      dependent molecules highly expressed in DHS1P-stimulated cells compared to S1P
      stimulated cells. Calcium mobilization analysis showed that DHS1P had higher
      magnitudes of intracellular calcium mobilization than S1P, suggesting that S1P
      and DHS1P differentially regulate intracellular calcium mobilization, possibly
      leading to different gene expression in mesangial cells. The large-scale
      monitoring of gene expression performed here allows us to identify S1P-induced
      transcriptional properties during mesangial cell proliferation.

PMID- 12504123
TI  - Increased expression of the nicotinic acetylcholine receptor in stimulated
      muscle.
AB  - Chronic low-frequency stimulation has been used as a model for investigating
      responses of skeletal muscle fibres to enhanced neuromuscular activity under
      conditions of maximum activation. Fast-to-slow isoform shifting of markers of the
      sarcoplasmic reticulum and the contractile apparatus demonstrated successful
      fibre transitions prior to studying the effect of chronic electro-stimulation on
      the expression of the nicotinic acetylcholine receptor. Comparative
      immunoblotting revealed that the alpha- and delta-subunits of the receptor were
      increased in 10-78 day stimulated specimens, while an associated component of the
      surface utrophin-glycoprotein complex, beta-dystroglycan, was not drastically
      changed in stimulated fast skeletal muscle. Previous studies have shown that
      electro-stimulation induces degeneration of fast glycolytic fibres, trans
      differentiation leading to fast-to-slow fibre transitions and activation of
      muscle precursor cells. In analogy, our results indicate a molecular modification
      of the central functional unit of the post-synaptic muscle surface within
      existing neuromuscular junctions and/or during remodelling of nerve-muscle
      contacts.

PMID- 12504124
TI  - Myofibrillar responsiveness to cAMP, PKA, and caffeine in an animal model of
      heart failure.
AB  - We investigated whether an alteration of myofilament calcium responsiveness and
      contractile activation may in part contribute to heart failure. A control group
      of Broad Breasted White turkey poults was given regular feed without additive,
      whereas the experimental group was given the control ration with 700 ppm of
      furazolidone at 1 week of age for 3 weeks (DCM). At 4 weeks of age, left
      ventricular trabeculae carneae were isolated from hearts and calcium-force
      relationships studied. No differences in calcium-activation between fibers from
      control or failing hearts were noted under standard experimental conditions. Also
      failing hearts demonstrated no significant shift in the population of troponin T
      isoforms but we did observe a significant 4-fold decrease in TnT content in
      failing hearts compared to non-failing hearts. Addition of caffeine, however,
      resulted in a greater leftward shift on the calcium axis in fibers from failing
      hearts. At pCa 6, caffeine increased force by 26+/-2.1% in control fibers and
      44.5+/-8.7% in myopathic fibers. Cyclic AMP resulted in a greater rightward shift
      on the calcium axis in failing myocardium. In control muscles, the frequency of
      minimum stiffness (f(min)) was higher than in muscles from failing hearts. cAMP
      and caffeine both shifted f(min) to higher frequencies in control fibers whereas
      in fibers from failing hearts both caused a greater shift. These results lead us
      to conclude that heart failure exerts differential effects on cAMP and caffeine
      responsiveness. Our data suggest that changes at the level of the thin
      myofilaments may alter myofilament calcium responsiveness and contribute to the
      contractile dysfunction seen in heart failure.

PMID- 12504125
TI  - Analysis of the 5' promoters for human IL-3 and GM-CSF receptor alpha genes.
AB  - The receptors for human interleukin-3 (hIL-3R) and granulocyte-macrophage colony
      stimulating factor (hGM-CSFR) consist of an alpha subunit, specific for each
      cytokine, and a beta subunit, common to IL-3, GM-CSF, and IL-5. We cloned genomic
      DNA covering 1.5 kb of the 5' flanking region of the hIL-3R alpha gene and
      identified multiple transcription start sites by 5(')-RACE and primer extension
      analyses. By use of transient transfection experiments, two regions (nt -363 to 
      331 and -106 to -92) of the hIL-3R alpha promoter appeared to have significant
      transcription-enhancing activities. Electrophoresis mobility shift assays
      revealed the binding of Sp1 and unidentified proteins to these regions. Deletion
      of a putative PU.1 binding site did not affect the promoter activity. We then
      analyzed 2.5 kb of the hGM-CSFR alpha gene and found the proximal PU.1 binding
      site to be important for transcription-enhancing activity, as previously
      reported. These results suggest that different transcriptional activation
      mechanisms are employed for the transcriptional regulation of hIL-3 and hGM-CSF
      receptor alpha genes.

PMID- 12504126
TI  - Small HIV-1-Tat peptides inhibit HIV replication in cultured T-cells.
AB  - Full-length soluble HIV-1 Tat protein has been shown to bind the CXCR4 receptor.
      Occupancy of CXCR4 by Tat inhibits infection of cells by T-tropic HIV-1. To
      understand if fragments of the Tat protein may have similar anti-HIV activity, we
      synthesized Tat peptides and tested their activity in tissue culture. Here, we
      report a sequence-specific contribution of Tat residues 31-35 to anti-HIV-1
      activity.

PMID- 12504127
TI  - Environmental properties and effects of nonionic surfactant adjuvants in
      pesticides: a review.
AB  - Little is known about the environmental fate of adjuvants after application on
      the agricultural land. Adjuvants constitute a broad range of substances, of which
      solvents and surfactants are the major types. Nonionic surfactants such as
      alcohol ethoxylates (AEOs) and alkylamine ethoxylates (ANEOs) are typically
      examples of pesticide adjuvants. In view of their chemical structure this paper
      outlines present knowledge on occurrence, fate and effect on the aquatic and
      terrestrial environment of the two adjuvants: AEOs and ANEOs. Both AEOs and ANEOs
      are used as technical mixtures. This implies that they are not one single
      compound but a whole range of compounds present in different ratios. Structurally
      both groups of substances have a mutual core with side chains of varying lengths.
      Each of these compounds besides having the overall ability to distribute between
      different phases also possesses some single compound behaviour. This is reflected
      in the parameters describing the fate e.g. distribution coefficient, leaching,
      run-off, adsorption to soil, degradation and effects of these substances. The
      adsorption behaviour of ANEOs in contrast to AEOs is particularly variable and
      matrix dependent due to the ability of the compound to ionise at environmentally
      relevant pH. Probably because the compounds exceeds high soil adsorption and are
      easily degradable which is reflected in the low environmental concentrations
      generally found in monitoring studies. The compounds generally possess low
      potency to both terrestrial and aquatic organisms. The major environmental
      problem related to these compounds is the ability to enhance the mobility of
      other pollutants in the soil column.

PMID- 12504128
TI  - Measurement of 13C/12C of chloroacetic acids by gas
      chromatography/combustion/isotope ratio mass spectrometry.
AB  - This paper describes a novel analytical methodology using gas
      chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to measure
      the 13C/12C ratios of chloroacetic acids (CAAs). CAAs are a major class of
      environmental pollutants that are widely distributed throughout the world, often
      at relatively high concentrations, and are of concern due to their toxic effects,
      particularly on plants. The 13C/12C of CAA reagents was measured by IRMS
      subsequent to offline combustion. Aqueous solutions of these CAAs were
      derivatized to the corresponding methyl chloroacetates (MCAAs) with acidic
      methanol with a known isotopic composition, extracted into pentane, and analyzed
      by GC/C/IRMS. Measured 13C/12C ratios of derivatized MCAAs were in agreement with
      calculated values within 1 per thousand for monochloroacetic acid and
      trichloroacetic acid and within 2 per thousand for dichloroacetic acid,
      suggesting that methylation and other analytical methodology steps do not
      isotopically fractionate derivatized MCAAs. 13C/12C ratios of reagent CAAs from
      different sources had varying isotopic signatures suggesting differences in
      source carbon and/or production methods. Our results underscore the potential of
      stable isotopes to serve as tracers of environmental sources of CAAs.

PMID- 12504129
TI  - Copper and zinc retention by an organically amended soil.
AB  - This paper describes changes in retention of Cu and Zn in laboratory experiments
      by a sandy soil that had been amended in the field with different composted
      wastes. The amounts of the metals retained increased as a result of the
      amendments, especially after two years. Desorption of the sorbed metals was
      always negligible, regardless of the treatment. The proportion of Cu retained was
      considerably higher than that of Zn, suggesting a higher affinity of the soil for
      the former. The greater sorption in the amended soils indicates a build-up of
      fresh sites for metal retention. The use of 'log(activity) vs. pH' plots showed
      that the nature of the surfaces retaining metals on the untreated and amended
      soils is different. At comparable pH values, the amended soils gave higher
      solution metal concentrations. Some of the possible environmental consequences of
      the use of these amendments for remediation purposes are discussed.

PMID- 12504130
TI  - Chemical and microbial hypotheses explaining the effect of wastewater treatment
      plant discharges on the nitrifying communities in freshwater sediment.
AB  - Nitrification is a microbial key step of the nitrogen cycle, which performs the
      oxidation of ammonium to nitrate, via nitrite. In aquatic environments, it mainly
      takes place in the sediment or is associated with suspended particles. Wastewater
      treatment plant (WTP) discharges in rivers may disrupt sediment nitrification:
      this impact is related to nitrogen inputs (mainly NH(4)(+) and organic nitrogen)
      but could also depend on the nitrifying bacteria inputs which have been proved to
      survive downstream WTP discharge points. The aim of the present study was to
      assess the effect of NH(4)(+) and nitrifying bacteria inputs on the two steps of
      nitrification in freshwater sediments. To avoid natural sites constraints and to
      control the main environmental parameters, we used microcosms to simulate a river
      receiving different types of WTP discharges. These microcosms were composed of
      five glass dual-walls reactors (6 l) containing sediment and continuously filled
      (controlled flow) with river water and WTP effluent. Two types of effluents were
      tested: a non-nitrified one (high NH(4)(+) input, very few nitrifying bacteria)
      and a nitrified one (low NH(4)(+) input, more nitrifying bacteria), at different
      effluent/freshwater ratios (0/100, 20/80, 40/60 and 80/20). Changes in the
      ammonium- and nitrite-oxidizing communities were assessed by the Most Probable
      Number method, and changes in potential ammonium-oxidizing activity and potential
      nitrite-oxidizing activity were determined by incubations with specific
      inhibitors (sodium chlorate and allylthiourea). In most of the cases the presence
      of effluent induced significant changes of the nitrifying bacteria densities and
      potential activities in the sediment. This effect indicates generally a loss of
      specific potential activity and in most of the time is significant for a high
      effluent/river water ratio (40% to 80%). In our experimental conditions and in
      the case of a large WTP discharge, the nitrifying potential in freshwater
      sediments could thus be significantly modified.

PMID- 12504131
TI  - Biodegradation of linear alkylbenzene sulfonates in sulfate-leached soil
      mesocosms.
AB  - Aromatic sulfonates (R-SO(3)(-)) can be used as sulfur sources by sulfate-starved
      bacteria in laboratory cultures and the corresponding phenols are excreted from
      the cells. The present study was conducted to demonstrate whether such
      desulfonation reactions also occur in sulfate-leached agricultural soil, where
      desulfonation of organic sulfur compounds may have agronomic importance as a S
      source for plants. Xenobiotic linear alkylbenzene sulfonates (LAS) were added to
      nominal concentrations of 0, 10 and 100 mgkg(-1) dry weight in a sandy soil that
      was depleted in sulfate by leaching the soil with water (sulfate depletion,
      approximately 75%). The soil was incubated at 20 degrees C in duplicate 3-dm(3)
      mesocosms for 8 weeks. Primary degradation of LAS was rapid with half-lives of 1
      4 days. Sulfophenylcarboxylates were identified and quantified as intermediates,
      whereas linear alkylphenols (the expected primary desulfonation products) were
      not detected by high-pressure liquid chromatography coupled with both
      fluorescence and electrospray ionization-mass spectrometry. Thus, LAS was used by
      the bacteria as a source of energy and carbon, rather than as a source of sulfur.
      Measurements of soil pH, fluorescein diacetate (FDA) hydrolysis and arylsulfatase
      activity showed that stable microbial conditions prevailed in the soil mesocosms.
      FDA hydrolysis (a measure of total microbial activity) was transiently inhibited
      at the highest LAS concentrations. Arylsulfatase activity (i.e., hydrolysis of
      aromatic sulfate esters) was not significantly affected by the soil incubation,
      although arylsulfatases may be upregulated in sulfate-starved bacteria. However,
      an increased production of arylsulfatase may be difficult to detect due to the
      background of extracellular arylsulfatases stabilised in the soil. Therefore, the
      present data does not exclude a regulatory response to sulfate depletion by the
      soil microorganisms. However, the importance of desulfonation reactions in
      natural environments still needs to be demonstrated.

PMID- 12504132
TI  - Multiple regression modelling of mineral base oil biodegradability based on their
      physical properties and overall chemical composition.
AB  - A set of 38 mineral base oils was characterized by a number of chemical (i.e.,
      overall chemical composition) and physical parameters used routinely in industry.
      Their primary biodegradability was evaluated using the CEC L-33-A-93 test.
      Multiple (stepwise) linear regression (MLR) analyses were performed to describe
      the relationships between the biodegradability values and the chemical or
      physical properties of oils. Chemical, physical, and both types of parameters
      were successively used as independent variables. Using chemical descriptors as
      variables, a four-variable model equation was obtained that explained only 68.2%
      (adjusted R-squared statistic=68.2%) of the variability in biodegradability. The
      fitting was improved by using either the physical or the whole parameters as
      variables. MLR analyses led to three-descriptor model equations involving
      kinematic viscosity (as log), Noack volatility (as log) and either the viscosity
      index (pure physical model) or the paraffinic carbon percentage (mixed chemical
      physical model). These two models displayed very similar adjusted R-squared
      statistics, of approximately 91%. Their predicting ability was verified using 25
      additional base oils or oil blends. For 80% of oils on a total of 63, the
      absolute percentage error on biodegradability predicted by either model was lower
      than 20%. Kinematic viscosity was by far the most influential parameter in the
      two models.

PMID- 12504133
TI  - QSAR modeling with the electrotopological state indices: predicting the toxicity
      of organic chemicals.
AB  - A quantitative structure-activity relationship model, based on the atom-type
      electrotopological state (E-state) indices, for the prediction of toxicity to
      fathead minnow for a diverse set of 140 organic chemicals is presented. Multiple
      linear regression and artificial neural network techniques were employed in the
      modeling of experimental toxicity (-logLC(50)) values ranging from 0.85 to 6.09.
      For the training set of 130 organic compounds a linear regression model with
      r(2)=0.84 and s=0.36 was obtained with 14 atom-type E-state indices. For the test
      set of 10 compounds, the corresponding statistics were r(2)=0.83 and s=0.47,
      respectively. Neural networks gave a significant improvement using the same set
      of parameters, and the standard deviations were s=0.31 for the training set and
      s=0.30 for the test set when an artificial neural network with five neurons in
      the hidden layer was used. The results clearly show that accurate models can be
      rapidly calculated for the prediction of toxicity for a diverse set of organic
      chemicals using easily calculated parameters.

PMID- 12504134
TI  - Remediation of waters contaminated with pentachlorophenol.
AB  - We describe a simple method of remediating waters contaminated with
      pentachlorophenol (PCP), which involves filtering the water through clean soil.
      The filtrate is contaminant free and no PCP can be extracted from the soil. If
      the soil it treated with dilute acid, the filtrate is still contaminant free but
      28.7% of the PCP can be extracted from the contaminated soil. Irradiating the
      soil with microwave energy either destroys or binds the PCP to the soil
      irreversibly such that none can be extracted after long periods of time.

PMID- 12504135
TI  - An on-road study to investigate fatigue in local/short haul trucking.
AB  - As a precursor to the present research, Hanowski et al. [FHWA Report no. FHWA-MC
      98-029. Office of Motor Carriers, Federal Highway Administration, Washington, DC,
      1998] conducted a series of focus groups in which local/short haul (L/SH) drivers
      provided their perspective on safety issues, including fatigue, in their
      industry. As a follow-up to the Hanowski et al. work, the effort presented here
      consisted of an on-road field study where in-service L/SH trucks were
      instrumented with data collection equipment. Two L/SH trucking companies and 42
      L/SH drivers participated in this research. The analyses focused on determining
      if fatigue is an issue in L/SH operations. Of primary interest were critical
      incidents (near-crashes) where L/SH drivers were judged to be at fault. The
      results of the analyses indicated that fatigue was present immediately prior to
      driver involvement in at-fault critical incidents. Though it is difficult to
      determine with certainty why fatigue was present, the results suggest that
      drivers' off-hours behavior likely played a significant role in the fatigue
      experienced on the job. Another key finding of this research is that a small
      percentage of drivers were responsible for a majority of the critical incidents.
      This finding suggests that driver selection and monitoring could potentially
      improve safety in L/SH operations.

PMID- 12504136
TI  - Correlation between modes of drinking and modes of driving as reported by
      students at two American universities.
AB  - This paper examines the correlates and predictors of driving under the influence
      behaviors (DUIBs) during the past month by college students. Measures of heavy
      episodic drinking, monthly drinking frequency, monthly drinking variance, monthly
      drinks per occasion and reported marijuana use are compared as predictors net of
      other predictive factors. A cross-sectional telephone survey was conducted with
      college students by a university social science research laboratory. Respondents
      attended two large public universities located in the southwestern part of the
      US. Participants included 803 randomly selected college students. The interview
      schedule included items from the Core Alcohol and Drug Survey and the College
      Alcohol Risk Assessment Guide. Several additional last-drinking-event items were
      also developed for the interview. Bivariate analyses indicate that marijuana use
      (past year), heavy episodic drinking, reports of DUIBs (driving under the
      influence or riding with a driver who is under the influence) in the past year,
      monthly frequency of drinking, the average number of drinks consumed when
      drinking and age are correlates of DUIBs during the past month. Multivariate
      analyses indicate past year DUIBs, monthly frequency of drinking and monthly
      marijuana use predicted recent DUIB.

PMID- 12504137
TI  - Risk perception of traffic participants.
AB  - This article analyzes the risk perception of traffic participants by making use
      of Prospect Theory. This methodology makes a conceptual distinction between the
      perception of risk and the perception of the outcome of an uncertain event. In
      the field of transport safety such a distinction is desirable, because risks are
      typically very low and thus sensitive to misperception by traffic participants.
      Taking into account such misperception will significantly improve estimates of
      the valuation of transport safety. The first empirical results show that the
      valuation of losses is well represented by a utility function that is concave in
      shape. Secondly, our preliminary results show that individuals base their choice
      mainly on the possible outcomes and not so much on probabilities whenever there
      are very small probabilities (say <or=1/100) and "bad outcomes" involved.

PMID- 12504138
TI  - A small area study of motor vehicle crash fatalities in Alberta, Canada.
AB  - This study examined the small area variation in motor vehicle crash fatality
      rates in the province of Alberta, Canada. Motor vehicle crash fatality rates per
      100000 population (1995-1997, inclusive) were determined for five geographic
      areas in the province. The rates showed substantial, statistically significant
      variation across areas, with fatality rates lowest in the urban areas of Calgary
      and Edmonton, and highest in the rural areas (south, central, and northern
      Alberta). Examination of area-level predictors-population density, impaired
      driving citation rates, education level, unemployment levels, and ethnicity
      showed that population density and impaired driving rates were associated with
      motor vehicle crash fatality rates. There was a five-fold difference in annual
      motor vehicle crash fatality rates between rural (22.9/100000) and urban areas
      (4.4/100000), whereas annual impaired driving rates were around 1.8% in rural
      areas, compared with 0.6% in urban areas. Because of multicollinearity problems,
      it was not possible to estimate a multivariable Poisson regression model. In
      conclusion, rural areas in the province of Alberta demonstrate a significantly
      higher motor vehicle crash fatality rate, compared with urban areas.

PMID- 12504139
TI  - Effect of the helmet act for motorcyclists in Thailand.
AB  - OBJECTIVES: This study investigated the effect of the helmet act for
      motorcyclists on increasing helmet use and reducing motorcycle-related deaths and
      severe injuries in Thailand. METHODS: Data were derived from a trauma registry at
      the Khon Kaen Regional Hospital in the northeast Thailand. Helmet use and outcome
      in motorcycle crashes were compared 2 years before (1994-1995) and after (1996
      1997) enforcement of the helmet act. During the study period, there were 12002
      injured motorcyclists including 129 death cases in the municipality of Khon Kaen
      Province who were brought to the regional hospital. RESULTS: After enforcement of
      the helmet act, helmet-wearers increased five-fold while head injuries decreased
      by 41.4% and deaths by 20.8%. Those who had head or neck injuries or died were
      less likely wearing a helmet. Compliance of helmet use was lower at night.
      Fatality of injured motorcyclists did not significantly decrease in the post-act
      period and among helmet-wearers. CONCLUSION: Enforcement of the helmet act
      increased helmet-wearers among motorcyclists but helmet use did not significantly
      reduce deaths among injured motorcyclists. Motorcyclists should be instructed to
      properly and consistently wear a helmet for their safety.

PMID- 12504140
TI  - Organisation of truck-driver training for the transportation of dangerous goods
      in Europe and North America.
AB  - In Canada, as in several other countries, truck drivers involved in the
      transportation of dangerous goods must be trained. However, given the many
      differences in vehicles, substances transported and driving conditions,
      international guidelines are very open-ended. This article outlines the domestic
      training requirements in Canada, the United States, The Netherlands and Sweden,
      and examines the manner in which the training is provided. In both Canada and the
      United States, the responsibility for assuring a driver is adequately trained
      rests with the employer. It is the employer who determines the duration and
      content of any training program. In addition, the assessment of a driver is also
      an employer responsibility. In practice, possibility in light of liability
      issues, many employers use commercial training firms. However, generally speaking
      there is no national or regional accreditation program for such commercial firms.
      In Europe, where training is conducted in response to the European Agreement
      concerning the International Carriage of Dangerous Goods by Road, training and
      testing must receive national accreditation, although the specific details of
      such accreditation are not spelled out. Sweden places its emphasis on careful
      accreditation of those providing training, while in The Netherlands more
      importance is placed on examinations to be used to test the results of the
      training. The intent of this article is to show that the same goal in four
      different countries has resulted in four different schemes, each of which appears
      to be accepted in the country of use. A comparison of safety achieved in the
      transportation of dangerous goods in each country is beyond the scope of this
      article. International evaluation studies would be necessary to draw
      scientifically-based conclusions on the effectiveness of truck-driver training
      systems for the safe transportation of dangerous goods.

PMID- 12504141
TI  - Correlation of head injury to vehicle contact points using crash injury research
      and engineering network data.
AB  - Head injury is the most common cause of morbidity and mortality in motor vehicle
      crashes. Efforts to improve vehicle design, which minimize forces exerted to the
      occupant's head, may lead to a reduction in the frequency and severity of head
      injury. We therefore set out to identify mechanisms producing severe head injury
      in motor vehicle crashes (MVC) derived from the crash injury research and
      engineering network (CIREN) database. CIREN combines crash site analysis, vehicle
      damage assessment, and occupant kinematics in relation to the occupant's
      injuries. From the Seattle CIREN database of 101 cases, compiled from 1997 to
      1998, we selected those crashes in which the occupant sustained severe head
      injury (abbreviated injury score, AIS>or=4) for analysis. We examined crash
      mechanism, energy transfer, point of head contact, vehicle intrusion and
      resulting injuries. There were 15 cases with severe head injury. These were
      primarily due to side impacts (n=10) in comparison to front impacts (n=5). The
      average net change in velocity (delta velocity, DV) was 15 mile/h (range 4-29
      mile/h). In cases where the primary point of head contact could be elucidated the
      B-pillar predominated (4 cases, 33.3%) followed by the striking external object
      (2 cases, 16.7%), A- (1 case, 8.3%) and C- (1 case, 8.3%) pillars, roof side rail
      (1 case, 8.3%), windshield header (1 case, 8.3%), windowsill (1 case, 8.3%) and
      airbag (1 case, 8.3%). In this series the predominant mechanism of head injury
      was lateral impacts, especially those in which the victims' heads struck the B
      pillar. The need for improved head protection from lateral impacts is indicated.

PMID- 12504142
TI  - The validity and reliability of a portable slip meter for determining floor
      slipperiness during simulated heel strike.
AB  - A previously developed test rig was used as starting point for designing a
      portable slip meter with two new features. First, an inflatable pneumatic test
      wheel, consisting of six slider units, was introduced as the impacting contact
      element relative to floor surface. Second, an inductive trigger was built into
      the system to facilitate a precise timing of the slider-floor contact during the
      test. This new test rig was designed to measure transitional friction properties
      of contaminated floor surfaces during simulated heel strike, which is considered
      the most critical phase of gait from the slip and fall point of view. Another
      objective was to quantify the validity and reliability of this test method in the
      laboratory, but not yet in the field. The measurement process was evaluated on
      eight wet and oily floor surfaces (vinyl and ceramic tile floorings) using two
      slider materials (plain, profiled), two normal loads (100, 200 N), and two
      sliding velocities (0.15, 0.30 m/s) as independent variables. The outputs of the
      portable slip meter, in terms of transitional friction coefficients, were
      compared to force platform-based friction values and to slip resistance values
      obtained with a slip simulator apparatus for laboratory testing of shoes and
      floor surfaces. The outputs were also evaluated against slipperiness ratings made
      by three male subjects in paired comparison trials, in which the subjects walked
      over eight wet floor surfaces wearing shoes with the plain soling material. The
      results showed that test option 200 N and 0.15m/s led to optimum validity despite
      its tendency to promote frictional vibrations (stick-slip) in the contact
      surface. Compared to the lower sliding speed, the higher speed reduced both stick
      slip and measurement bias. Test option 200 N and 0.30 m/s was the most reliable
      one in this experiment. It yielded lower friction coefficients than any other
      test option and reduced the likelihood of underestimating slip and fall hazards.
      The results implied that the minimum friction coefficient was 0.25 for preventing
      a fall on wet floor surfaces, whereas the limit for preventing a slip was in the
      range 0.30-0.35. Transitional friction measurement was found to be a valid and
      reliable indicator for slip resistance. A more accurate control of the normal
      force during testing is needed for actual field use of the test method.

PMID- 12504143
TI  - Fragility versus excessive crash involvement as determinants of high death rates
      per vehicle-mile of travel among older drivers.
AB  - Using multiple national data systems, the roles of fragility (susceptibility to
      injury) versus excessive crash involvement in the increased fatality risk of
      older drivers per vehicle-mile of travel (VMT) were estimated. For each age and
      gender group, deaths per driver involved in a crash (a marker of fragility) and
      drivers involved in crashes per VMT (a marker of excessive crash involvement)
      were computed. Compared with drivers ages 30-59, those younger than 20 and those
      75 or older both had much higher driver death rates per VMT. The highest death
      rates per mile driven, 13-fold increases, were observed among drivers age 80 or
      older, who also had the highest death rates per crash. Fragility began to
      increase at ages 60-64 and increased steadily with advancing age, accounting for
      about 60-95% of the excess death rates per VMT in older drivers, depending on age
      group and gender. Among older drivers, marked excesses in crash involvement did
      not begin until age 75, but explained no more than about 30-45% of the elevated
      risk in this group of drivers; excessive crashes explained less of the risk among
      drivers ages 60-74. In contrast, crash over-involvement was the major factor
      contributing to the high risk of death among drivers younger than 20, accounting
      for more than 95% of their elevated death rates per VMT. Although both fragility
      and crash over-involvement contributed to the excess death rates among older
      drivers per VMT, fragility appeared to be of over-riding importance. These
      findings suggest that measures to improve the protection of older vehicle
      occupants in crashes should be vigorously pursued.

PMID- 12504144
TI  - Impact of safety belt use on road accident injury and injury type in Kuwait.
AB  - The enactment of Kuwait's seat belt law in January 1994 provided an opportunity
      to examine the impact of seat belt use on road accident fatalities and injury
      types in this affluent Persian Gulf nation. Via a structured data form, the
      results of injurious/fatal road accidents for more than 1200 accident victims
      were gathered from the files of the six major government hospitals which treat
      most traffic accident victims. Statistical analysis of the data showed that seat
      belt use has had a positive effect in reducing both road traffic fatalities and
      multiple injuries in Kuwait. The use of seat belts has also affected the nature
      of the injuries resulting from road traffic accidents. Non-users of belts
      experienced higher frequencies of head, face, abdominal and limb injuries. Users
      of belts, on the other hand, suffered higher frequencies of neck and chest
      injuries. The interrelationship between the victim, his age, and the type of
      injuries resulting from road traffic accidents is also investigated.

PMID- 12504145
TI  - A longitudinal study of risk factors for motorcycle crashes among junior college
      students in Taiwan.
AB  - A cohort of 4729 junior college students in an urban and a rural area in Taiwan
      was followed up for a period of 20 months. Students' characteristics, including
      riding exposures, as well as human, vehicular, and environmental factors were
      collected using one initial and three follow-up questionnaires. The Anderson-Gill
      (AG) multiplicative intensity model was used to determine the risk of a
      motorcycle crash over time while also allowing for the modeling of multiple
      events. The average response rate for the four assessments was 92%. The adjusted
      relative hazard (RH) for students living in the rural as opposed to the urban
      area for crashes was 1.67 at the beginning of the study but decreased to 0.66 by
      the end. Past motorcycle crash history, number of riding days, average riding
      distance, risk-taking level, alcohol consumption, and traffic violations were all
      significantly associated with an increased risk of being involved in a crash.
      Conversely, increasing age, riding experience, and automobile licensure were
      related to a decreased risk of crashing. Furthermore, helmet use was not
      independently related to the risk of crashing. In conclusion, a high-risk group
      predisposed to involvement in a motorcycle crash, including both non-injury and
      injury-related crashes, can be identified using selected risk factors for crash
      prevention among young riders.

PMID- 12504146
TI  - Applying the random effect negative binomial model to examine traffic accident
      occurrence at signalized intersections.
AB  - Poisson and negative binomial (NB) models have been used to analyze traffic
      accident occurrence at intersections for several years. There are however,
      limitations in the use of such models. The Poisson model requires the variance-to
      mean ratio of the accident data to be about 1. Both the Poisson and the NB models
      require the accident data to be uncorrelated in time. Due to unobserved
      heterogeneity and serial correlation in the accident data, both models seem to be
      inappropriate. A more suitable alternative is the random effect negative binomial
      (RENB) model, which by treating the data in a time-series cross-section panel,
      will be able to deal with the spatial and temporal effects in the data. This
      paper describes the use of RENB model to identify the elements that affect
      intersection safety. To establish the suitability of the model, several goodness
      of-fit statistics are used. The model is then applied to investigate the
      relationship between accident occurrence and the geometric, traffic and control
      characteristics of signalized intersections in Singapore. The results showed that
      11 variables significantly affected the safety at the intersections. The total
      approach volumes, the numbers of phases per cycle, the uncontrolled left-turn
      lane and the presence of a surveillance camera are among the variables that are
      the highly significant.

PMID- 12504147
TI  - Age and sex differences in the risk of causing vehicle collisions in Spain, 1990
      to 1999.
AB  - This retrospective, paired case-control study was designed to estimate crude and
      adjusted effects of age and sex on the risk of causing collisions between
      vehicles with four or more wheels in Spain during the period from 1990 to 1999.
      We selected all 220284 collisions registered from 1990 to 1999 in the Spanish
      Direccion General de Trafico (DGT) traffic crash database in which only one
      driver committed any infraction. Information was collected about age, sex and
      several confounding factors for both the responsible and paired-by-collision
      nonresponsible drivers. Crude and adjusted odds ratios (aORs) were calculated for
      each age and sex category. For men, the lowest risk was seen for drivers aged 25
      49 years. Below the age of 35 years the crude odds ratio (cOR) was highest in the
      18-24-year-old group (1.61; CI: 1.57-1.65). The risk increased significantly and
      exponentially after the age of 50 years, to a maximum odds ratio of 3.71 (3.43
      4.00) for drivers aged >74 years. In women, the lowest risk values were found for
      the 25-44-year-old age group. In older women the risk increased significantly
      with age to a maximum odds ratio of 3.02 (2.31-3.97) in the oldest age group. aOR
      estimates tended to be lower than crude estimates for drivers younger than 40
      years of age, but the opposite was seen for drivers 40 years old and older.
      Regarding sex differences, among younger drivers crude and aORs for men were
      higher than for women. Our results suggest that the risk of causing a collision
      between vehicles with four or more wheels is directly dependent on the driver's
      age.

PMID- 12504148
TI  - Accident prediction models for urban roads.
AB  - This paper describes some of the main findings from two separate studies on
      accident prediction models for urban junctions and urban road links described in
      [Uheldsmodel for bygader-Del1: Modeller for 3-og 4-benede kryds. Notat 22, The
      Danish Road Directorate, 1995; Uheldsmodel for bygader- Del2: Modeller for
      straekninger. Notat 59, The Danish Road Directorate, 1998] (Greibe and Hemdorff,
      1995, 1988). The main objective for the studies was to establish simple,
      practicable accident models that can predict the expected number of accidents at
      urban junctions and road links as accurately as possible. The models can be used
      to identify factors affecting road safety and in relation to 'black spot'
      identification and network safety analysis undertaken by local road authorities.
      The accident prediction models are based on data from 1036 junctions and 142 km
      road links in urban areas. Generalised linear modelling techniques were used to
      relate accident frequencies to explanatory variables. The estimated accident
      prediction models for road links were capable of describing more than 60% of the
      systematic variation ('percentage-explained' value) while the models for
      junctions had lower values. This indicates that modelling accidents for road
      links is less complicated than for junctions, probably due to a more uniform
      accident pattern and a simpler traffic flow exposure or due to lack of adequate
      explanatory variables for junctions. Explanatory variables describing road design
      and road geometry proved to be significant for road link models but less
      important in junction models. The most powerful variable for all models was motor
      vehicle traffic flow.

PMID- 12504149
TI  - The efficacy of bicycle helmets against brain injury.
AB  - An examination is made of a meta-analysis by Attewell, Glase and McFadden which
      concludes that bicycle helmets prevent serious injury, to the brain in
      particular, and that there is mounting scientific evidence of this. The
      Australian Transport Safety Bureau (ATSB) initiated and directed the meta
      analysis of 16 observational studies dated 1987-1998. This examination
      concentrates on injury to the brain and shows that the meta-analysis and its
      included studies take no account of scientific knowledge of its mechanisms.
      Consequently, the choice of studies for the meta-analysis and the collection,
      treatment and interpretation of their data lack the guidance needed to
      distinguish injuries caused through fracture of the skull and by angular
      acceleration. It is shown that the design of helmets reflects a discredited
      theory of brain injury. The conclusions are that the meta-analysis does not
      provide scientific evidence that such helmets reduce serious injury to the brain,
      and the Australian policy of compulsory wearing lacks a basis of verified
      efficacy against brain injury.

PMID- 12504150
TI  - Risk assessment of sensory irritants in indoor air--a case study in a French
      school.
AB  - Exposure to airborne pollutants can result in adverse health effects. Acute
      symptoms can for instance comprise of irritation of the eyes or of the
      respiratory tract (called sensory irritation). In a recent case, health problems
      were reported in a French school and supposedly attributed to the presence of
      airborne irritant pollutants. Based on measured concentrations, the risk of
      developing the described health effects was assessed. Numerous airborne sensory
      irritants (aldehydes, organic acids, volatile organic compounds (VOCs), SO(2),
      NH(3)) were identified and quantified in the indoor air by using active and
      passive sampling and online monitoring techniques. Reference values based on
      toxicological properties of compounds (sensory irritants) were taken from the
      literature. If not available, tentative values were specially developed for this
      purpose. Concentrations of all sensory irritants remain below their corresponding
      guideline values and are comparable to literature data. It was concluded that the
      risk of developing sensory irritation due to the presence of the studied
      compounds is negligible. This holds both for individual compounds and for the
      mixture of studied compounds. Limitations of the employed sampling strategy, and
      of existing sampling and analytical techniques, which do not allow for analysing
      more reactive compounds-which are strong sensory irritants-may play a role. New
      sampling techniques need to be developed. Psychosocial factors (group behaviour,
      increased attention to sensory irritation) should also be taken into account when
      dealing with health complaints on sensory irritation.

PMID- 12504151
TI  - Levels and congener pattern of polychlorinated biphenyls in the blubber of the
      Mediterranean bottlenose dolphins Tursiops truncatus.
AB  - Isomer specific concentrations of individual polychlorinated biphenyls (PCBs)
      including toxic non-ortho (IUPAC 77, 126, 169) and mono-ortho (105, 118, 156)
      coplanar congeners were determined in the blubber of nine bottlenose dolphins
      (Tursiops truncatus) stranded along the Eastern Italian coast. The total PCB
      concentrations ranged from 3534 to 24375 ng/g wet wt. The PCB profile was
      dominated by congeners 138 and 153 collectively accounting for 55% of the total
      PCB concentrations. Among the most toxic congeners the order of abundance was
      126>169>77. The mean total 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent
      of six coplanar PCBs in the blubber of bottlenose dolphins was 45596 pg/g. Non
      ortho congeners contributed greater to the 2,3,7,8-TCDD toxic equivalents than
      mono-ortho members. Particularly, PCB 126 was the major contributor to the
      estimated toxic potency of PCBs in dolphins.

PMID- 12504152
TI  - Cancer cluster among police detachment personnel.
AB  - An apparent cancer cluster at a police detachment in a coastal British Columbia
      community was investigated. Police personnel suspected that the detachment
      building may have been a factor. Police personnel (20 current and 154 previous
      employees) associated with the detachment since 1963, the date of occupancy, were
      traced. After all 174 cases were contacted directly, or next of kin in case of
      death, a total of 16 cases of cancer or suspected cancers were reported. Of these
      16, eight cases of cancer were confirmed through a cancer registry. Cancers
      included testicular, cervical, colon, skin (including melanoma), leukemias and
      lymphomas with an age range of diagnosis between 22 and 44 years. There was no
      evidence for an underlying event, factor or condition in the police building that
      could be attributed to the observed cancer cases. A possible association between
      these cancers and the use of police traffic radar is discussed.

PMID- 12504153
TI  - Photo-oxidation products of petroleum hydrocarbons in the Eastern Red Sea coastal
      waters.
AB  - The level of dissolved oil residues as well as the oxygenated petroleum
      hydrocarbons in the seawater of the affected area of Jeddah coast, Red Sea was
      estimated. The dissolved/dispersed petroleum hydrocarbons concentration was found
      minimal. The minimum level may be attributed to the action of the weathering
      processes. Selected samples of the dichloromethane extracts of seawater were
      fractionated, using silica gel columns, into four fractions eluted with solvents
      of increasing polarity. The fluorescence intensity of these fractions was
      measured at three different pairs of excitation and emission wavelengths using
      ultraviolet fluorescence spectrofluorophotometry (UVF). The total fluorescence
      intensity of the fractions at 280 nm excitation, 327 nm emission wavelengths and
      310 nm excitation, 360 nm emission wavelengths exceeds the fluorescence intensity
      of the whole extract by more than two orders of magnitude. The estimation of
      higher molecular mass oxygenated compounds in the fourth fractions, read at 380
      nm excitation, 430 nm emission wavelengths, indicates rather low concentrations
      of <1 microg l(-1) hydroxypyrene equivalents. However, the polar fractions
      (eluted with acetone) account for more than 25% of the total fluorescence
      intensity of all fractions combined at each pair of wavelengths. The
      characterization of the products causing the fluorescence particularly the high
      molecular mass compounds still presents difficulties. Preliminary GC/MS results
      revealed some evidence for petroleum hydrocarbon oxidation products. Alkyl
      isobenzofuranones have been found in some seawater extracts. This is an ongoing
      project to characterize and identify additional compounds from these extracts.

PMID- 12504154
TI  - Pollution load of Pb, Zn, and Cd and mineralogy of the recent sediments of Jordan
      River/Jordan.
AB  - The present geochemical analyses of Zn, Pb and Cd in eighteen subsurface sediment
      samples collected from two locations along the Jordan River show that Cd is
      anthropogenically enriched in these sediments. In the sediment column, the
      concentration of Zn, Pb and Cd decreases clearly with depth in the first location
      of the upper reach, due to the high rate of sedimentation in this location;
      whereas the enrichment of elements of the lower reach increases gradually towards
      the old sediments. The Anthropogenic factor of the studied metals lies in the
      sequence of Pb>Cd>Zn.

PMID- 12504155
TI  - Bacterial antibiotic resistance levels in Danish farmland as a result of
      treatment with pig manure slurry.
AB  - Resistance to tetracycline, macrolides and streptomycin was measured for a period
      of 8 months in soil bacteria obtained from farmland treated with pig manure
      slurry. This was done by spread plating bacteria on selective media (Luria
      Bertani (LB) medium supplemented with antibiotics). To account for seasonal
      variations in numbers of soil bacteria, ratios of resistant bacteria divided by
      total count on nonselective plates were calculated. Soil samples were collected
      from four different farms and from a control soil on a fifth farm. The control
      soil was not amended with animal manure. The occurrence of tetracycline-resistant
      bacteria was elevated after spread of pig manure slurry but declined throughout
      the sampling period to a level corresponding to the control soil. Higher load of
      pig manure slurry yielded higher occurrence of tetracycline resistance after
      spreading; however, the tetracycline resistance declined to normal occurrence
      defined by the tetracycline resistance occurrence in the control soil.
      Concentrations of tetracycline in soil and in pig manure slurry were measured
      using HPLC. No tetracycline exceeding the detection limit was found in soil
      samples. Manure slurry concentrations of tetracycline for three of the farms were
      42, 81 and 698 microg/l, respectively. For streptomycin and macrolides, only
      minor variations in resistance levels were detected. Results obtained in this
      study thus indicate that tetracycline resistance levels in soil are temporarily
      influenced by the addition of pig manure slurry. The results indicate also that
      increased amount of pig manure slurry amendment may result in increased levels of
      tetracycline resistance in the soil.

PMID- 12504156
TI  - A holistic approach to Concentration Assessment of hazards in the risk assessment
      of landfill leachate.
AB  - Risk assessment is a new research area. The risk assessment research area deals
      with a wide range of issues other than landfills. Examples of these issues are
      Radiation, Food Industry, Ecology, Epidemiology, etc. The authors have found that
      there are generic elements in risk assessment and these elements are independent
      of the subject areas mentioned above. An important example of these generic
      elements is the Concentration Assessment of hazards and is equally important from
      the perspective of landfill risk assessment. Furthermore, in the literature
      review of landfill risk assessment approaches, no evidence has been discovered of
      a holistic risk assessment methodology for landfill gas, leachate, or degraded
      landfill waste. A range of knowledge deficiencies has been found in the
      literature reviewed to date. One of these deficiencies in knowledge is the lack
      of a holistic procedure for carrying out Concentration Assessment. From the
      perspective of landfill leachate, this paper discusses the extent to which the
      Concentration Assessment of hazards is absent in landfill risk assessment
      approaches described in the literature reviewed to date, and the elements that
      should be added to the procedure of the Concentration Assessment in order to
      enhance the process of risk assessment. The paper also briefly outlines a
      holistic procedure for the Concentration Assessment and a corresponding computer
      model for the risk assessment of landfill leachate.

PMID- 12504157
TI  - Health assessment of a marine bivalve Ruditapes decussatus from the Gulf of Gabes
      (Tunisia).
AB  - Metallothioneins (MTs), malonedialdehyde (MDA), and glycogen concentrations were
      determined in order to assess the health status of Ruditapes decussatus exposed
      to in situ contamination, showing the effects of time, site, and metal
      contamination on these three biomarkers. Metallothionein was positively
      correlated with Cd and Zn. If introduced in a multiple model, the factors site
      and time were shown to decrease significantly MT concentrations. MDA was
      inversely correlated with size of the animals and was affected by the factor
      time. Glycogen was inversely correlated with zinc and was affected by both site
      and time.This study constitutes a field-based validation of a multiparametric
      approach using specific and nonspecific biomarkers.

PMID- 12504158
TI  - Distribution of heavy metals in sediments of Mwanza Gulf of Lake Victoria,
      Tanzania.
AB  - Sediment samples were analyzed for Cd, Cr, Cu, Pb, Hg and Zn by AAS. The highest
      concentrations (ppm) for Cu (26.1+/-4.8), Hg (0.2+/-0.05), Pb (30.7+/-5.6) and Zn
      (45.4+/-13.1) were found at approximately 25 m from the shoreline. Generally,
      heavy metals concentration in the sediment decreased with increasing distance
      from the shoreline except for Cd and Cr whose highest concentrations were found
      at approximately 2000 m from the shoreline. The data also indicated that sediment
      samples which were collected at the shores within the urban area of Mwanza showed
      elevated levels of Pb (54.6+/-11.1 ppm) and Zn (83.7+/-21.5 ppm). However, the
      highest concentrations of Cd (7.0+/-2.1 ppm), Cr (12. 9+/-1.0 ppm) and Hg (2.8+/
      0.8 ppm) were recorded at sampling stations which were adjacent to river mouths.

PMID- 12504159
TI  - Lead and cadmium levels in coastal benthic algae (seaweeds) of Tenerife, Canary
      Islands.
AB  - Lead and cadmium levels of some species of brown-algae (Phaeophyta) from the
      mesolittoral (intertidal area) of the Island of Tenerife (central-eastern
      Atlantic) were determined by Atomic Absorption Spectrometry. The quality control
      was carried out using a standard "CRM 279 Ulva lactuca". The mean, minimum and
      maximum concentrations were 11.21, 2.090 and 81.795 microg/g/dw; and 1.13, 0.190
      and 5.130 microg/g/dw for lead and cadmium, respectively. The fact that samples
      registering the highest cadmium concentrations were the same as those which
      showed the highest lead level corresponding to a sampling station nearby an urban
      water outlet could be relevant.

PMID- 12504160
TI  - Effects of 17alpha-ethinylestradiol on the reproduction of the cladoceran species
      Ceriodaphnia reticulata and Sida crystallina.
AB  - Single-species tests allow the assessment of chronical effects of endocrine
      disruptors on organisms under laboratory conditions. In the current study, three
      generation tests with Ceriodaphnia reticulata and Sida crystallina were carried
      out to examine the influence of the synthetic hormone 17alpha-ethinylestradiol
      (EE) on the reproduction of these cladoceran species. For each species, six
      different concentrations (10-500 microg/l EE) and two controls were tested with
      eight replicates for a duration of 4 weeks. The test was initiated by
      transferring one neonate individual into a test vessel which was incubated under
      standardized conditions. Every 2 days, the medium was renewed and life history
      parameters such as survivorship of the adults and juveniles, clutch size, first
      appearance and number of produced offspring were investigated. Acute toxicity
      tests showed that C. reticulata (EC50 (24 h) 1814 microg/l) was more sensitive
      towards the substance compared to S. crystallina (EC50 (24 h) >4100 microg/l).
      The juvenile phase of S. crystallina was significantly shorter at concentrations
      above 100 microg/l EE. For C. reticulata, 17alpha-ethinylestradiol caused a
      higher mortality of the newly hatched juveniles at EE concentrations above 200
      microg/l. No effects were found for mortality of adult animals, birth rate,
      number of juveniles per female and net reproduction rate of S. crystallina and C.
      reticulata. Thus, sublethal effects on parental generation exposed to EE lead to
      disturbances in reproduction and to affection of their offspring. Negative
      consequences for the population dynamic cannot be excluded, e.g. the decrease of
      a population.

PMID- 12504161
TI  - Heavy metals in sediments from Makupa and Port-Reitz Creek systems: Kenyan Coast.
AB  - Copper, zinc, lead and cadmium heavy metals were determined in sediments from the
      Kenyan Coast. Sediment samples were obtained from Makupa and Port Reitz Creek
      systems. The samples were digested using concentrated hydrochloric acid and the
      metal content determined using Atomic Absorption Spectrophotometer (AAS). The
      method of analysis was evaluated using Soil-7 certified reference material
      (International Atomic Energy Agency, IAEA). For comparison, sediment samples were
      also analysed using Energy Dispersive X-ray fluorescence technique and results
      obtained show good agreement. Higher metal concentrations were obtained in Makupa
      Creek sediments (Cu, 102+/-46.0; Zn, 1017+/-840; Pb, 103+/-35.8; Cd, 51.0+/-14.3)
      as compared to Port Reitz Creek system (Cu, 21.6+/-7.1; Zn, 57.1+/-17.9; Pb,
      26.2+/-11.6; Cd, 1.38+/-0.7). There was significant (p=0.05) variation in the
      elemental concentrations between and within sites. Industrial activities and a
      nearby municipal dumpsite were associated with the higher elemental
      concentrations particularly in Makupa Creek.

PMID- 12504162
TI  - Particulate and dissolved elemental loads in the Kuji River related to discharge
      rate.
AB  - In order to investigate influences of discharge rates on fluvial transport
      behavior of elements in the Kuji River, Japan, suspended and dissolved phase
      concentrations in the river water were measured together with the water flow
      rates. The concentrations of suspended particulate matter (SPM) increased by two
      or three orders of magnitude with the water discharge, and also had seasonal
      variations. Adsorptive elements or heavy metal elements, which tend to form
      insoluble compounds, were present generally as suspended forms in the river
      waters, and their dissolved form concentrations tended to increase with the water
      discharge. On the other hand, non-adsorptive elements such as alkali and alkaline
      earth elements were present as dissolved forms under a normal flow rate
      condition, but equivalent quantity of suspended species also occurred under a
      high flow condition. In this case, the dissolved form concentrations decreased
      with the water discharge. Characterization of SPM with analyses of chemical
      compositions, scanning electron microscopy (SEM) and X-ray diffractometry (XRD)
      indicated that clay mineral such as montmorillonite would be the main carrier
      material of trace and major elements during the fluvial transport in the Kuji
      River. Variations of contents of selected elements in SPM with the water
      discharge indicated that river bottom sediments, which are probably potential
      sources of SPM added due to high water flow rates, would be different in chemical
      compositions from SPM floating under a normal flow condition. Variations of
      chemical compositions of SPM as well as of suspended or dissolved form
      concentrations of elements in the river waters were formulated as a function of
      the water discharge rates.

PMID- 12504163
TI  - Characteristics of the PAH emissions from the incineration of livestock wastes
      with/without APCD.
AB  - This study was conducted on two batch-type livestock waste incinerators,
      including the one with an air-pollution control device (APCD)-one wet scrubber
      (WSB) and the other without APCD for the disposal of livestock wastes. The
      concentration and composition of 21 individual polycyclic aromatic hydrocarbons
      (PAHs) in the stack flue gas (gas and particle phases), bottom ash, and effluent
      of WSB were determined. Stack flue gas samples were collected by a PAH stack
      sampling system. Twenty-one individual PAHs were analyzed by a gas
      chromatography/mass spectrometer (GC/MS). Due to the low combustion temperature,
      a remarkable and significant increase in the total-PAH concentration of emission
      from the stack with APCD was observed when compared with the case without APCD.
      Measured total-PAH emission factors were 285 and 2.86 mg/kg waste for the
      incineration with and without APCD, respectively, while BaP (the most
      carcinogenic PAH) emission factors were 0.79 and 0.12 mg/kg waste for the
      incineration with and without APCD. The total-PAH output/input mass ratios
      averaged 0.011 and 0.004 with and without APCD, respectively. The result reveals
      that the PAH content in the auxiliary fuel during the incinerating process could
      affect the emission of PAH.

PMID- 12504164
TI  - Review of the oral toxicity of polyvinyl alcohol (PVA).
AB  - Polyvinyl alcohols (PVA) (CAS no. 9002-89-5) are synthetic polymers used in a
      wide range of industrial, commercial, medical and food applications. The purpose
      of this review, this critical evaluation of the available information on PVA, is
      to support the safety of PVA as a coating agent for pharmaceutical and dietary
      supplement products. All the available information on PVA gleaned from a
      comprehensive search of the scientific literature were critically evaluated.
      Orally administered PVA is relatively harmless. The safety of PVA is based on the
      following: (1) the acute oral toxicity of PVA is very low, with LD(50)s in the
      range of 15-20 g/kg; (2) orally administered PVA is very poorly absorbed from the
      gastrointestinal tract; (3) PVA does not accumulate in the body when administered
      orally; (4) PVA is not mutagenic or clastogenic; and (5) NOAELs of orally
      administered PVA in male and female rats were 5000 mg/kg body weight/day in the
      90-day dietary study and 5000 mg/kg body weight/day in the two-generation
      reproduction study, which was the highest dose tested. A critical evaluation of
      the existing information on PVA supports its safety for use as a coating agent
      for pharmaceutical and dietary supplement products.

PMID- 12504165
TI  - Factors determining percutaneous metal absorption.
AB  - Metals play a vital role in human, animal and plant physiology, and important
      research, past and ongoing, is directed towards exploring the interrelated
      mechanisms that govern their penetration through skin. Much insight has been
      gained through these efforts, but our understanding of the process is still
      incomplete, mainly due to the failure to allow for the effects of chemical
      speciation of metallic elements, especially the transition metals. Also, the skin
      as target organ presents imponderable and wide margins of variability. In vivo
      permeability is subject to homeostasis regulating the overall organism; in vitro,
      the sections of skin used for diffusion experiments are likely to present
      artifacts. Endeavors to define rules governing skin penetration to give
      predictive quantitative structure-diffusion relationships for metallic elements
      for risk assessment purposes have been unsuccessful, and penetration of the skin
      still needs to be determined separately for each metal species, either by in
      vitro or in vivo assays. Phenomena observed by us and other investigators, which
      appear to determine the process of skin permeation for a number of metals, are
      reviewed, separating the exogenous factors from the characteristics of the skin
      or other endogenous factors.

PMID- 12504166
TI  - Lack of in vivo clastogenic activity of grape seed and grape skin extracts in a
      mouse micronucleus assay.
AB  - Meganatural brand grape seed extract (GSE) and grape skin extract (GSKE),
      containing proanthocyanidin polyphenolic compounds, are intended for use in food
      as functional ingredients exhibiting antioxidant activity. Proanthocyanidins, as
      well as the minor constituent phenolic compounds in GSE and GSKE, are present
      naturally in many foods such as fruits, vegetables, chocolate, tea, etc., and on
      average people consume 460-1000 mg/day of these combined substances. While some
      polyphenolic compounds, tested individually, have demonstrated antitumorigenic or
      antipromotional activity, at least one minor component of GSE and GSKE,
      quercitin, has exhibited positive activity in Salmonella and other in vitro
      mutagenicity assays. As part of a program to investigate the safety of GSE and
      GSKE, these products were tested for in vivo clastogenic activity and/or
      disruption of the mitotic apparatus by detecting micronuclei in polychromatic
      erythrocyte (PCE) cells in Crl:CD-1(ICR) BR mouse bone marrow. The appropriate
      test article was dissolved in 0.5% carboxymethylcellulose and dosed by oral
      gavage to five males/test article/dose level/harvest time point. Animals were
      dosed at 500, 1000 and 2000 mg/kg. Five animals dosed with either test article at
      500, 1000 and 2000 mg/kg dose levels and five animals dosed with the
      cyclophosphamide (80 mg/kg) positive control were euthanized approximately 24 h
      after dosing for extraction of bone marrow. Five animals dosed with either test
      article at the 2000 mg/kg dose level and five animals dosed with the vehicle
      control article were euthanized approximately 24 and 48 h after dosing for
      extraction of bone marrow. At least 2000 PCEs per animal were analyzed for
      frequency of micronuclei. Cytotoxicity was assessed by scoring the number of PCEs
      and normochromatic erythrocytes (NCEs) in at least the first 500 erythrocytes for
      each animal. For both GSE and GSKE, no statistically significant increase in
      micronucleated PCEs was observed at any dose level or harvest time point. GSE
      produced indication of cytotoxicity (decreased PCE:NCE ratio) at the 2000 mg/kg
      dose level for the 48-h harvest time point, confirming that the test article
      reached the target bone marrow in significant amount. Meganatural GSE and
      Meganatural GSKE were evaluated as negative in the mouse bone marrow micronucleus
      assay under the conditions of this assay.

PMID- 12504167
TI  - Analysis of oxidative DNA damage after human dietary supplementation with
      linoleic acid.
AB  - It has been hypothesized that oxygen radicals generated by peroxidation of
      dietary linoleic acid may induce genetic damage and thereby increase cancer risk.
      We examined the effect of dietary supplementation with linoleic acid on the
      levels of oxidative DNA damage in peripheral lymphocytes and on the blood plasma
      antioxidant potential. Thirty volunteers received during 6 weeks either a high
      dose of linoleic acid (15 g/day), an intermediate dose of linoleic acid (7.5
      g/day) or an isocaloric supplement without linoleic acid (15 g palmitic
      acid/day). After the intervention, no significant increase in oxidative DNA
      damage, measured as relative amounts of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8
      oxodG) in DNA from peripheral lymphocytes, was observed in both high and
      intermediate linoleic acid-supplemented groups (increase of respectively 13 and
      21%; P>0.05). Also, the differences between levels of oxidative DNA damage in the
      high or intermediate linoleic acid-supplemented group and the control group
      receiving palmitic acid (23% decrease) were not significant. Furthermore, no
      statistically significant differences were found between the total antioxidant
      capacities of blood plasma from the different experimental groups. Plasma levels
      of malondialdehyde, an important end-product of lipid peroxidation, were not
      increased after supplementation, nor were effects found on the plasma
      concentrations of retinol, alpha-tocopherol and beta-carotene. Despite the
      experimental design that excludes several forms of bias introduced in studies
      based on modulation of dietary composition, our results provide no indication of
      increased oxidative stress or genetic damage as a result of increased dietary
      intake of linoleic acid. Therefore, we see no scientific basis to reconsider the
      public health policy to stimulate the intake of polyunsaturated fatty acids aimed
      at the reduction of coronary heart diseases.

PMID- 12504168
TI  - In vitro metabolism of the glycosidic sweeteners, stevia mixture and
      enzymatically modified stevia in human intestinal microflora.
AB  - Stevia mixture, sweeteners extracted from the leaves of Stevia rebaudiana
      Bertoni, consists mainly of stevioside and rebaudioside A (glycosides of the
      diterpene derivative steviol). The aim of this study was to investigate human
      intestinal metabolism of stevia mixture and its alpha-glucose derivative (known
      in Japan as enzymatically modified stevia) by LC/MS/ESI analysis. Degradation was
      examined by incubating stevia mixture, enzymatically modified stevia, stevioside,
      rebaudioside A, alpha-monoglucosylstevioside, alpha-monoglucosylrebaudioside A
      and the aglycone, steviol with pooled human faecal homogenates (obtained from
      five healthy volunteers) for 0, 8 and 24 h under anaerobic conditions. Stevia
      mixture, enzymatically modified stevia, stevioside and rebaudioside A (0.2 mg/ml)
      were completely eliminated within 24 h, whereas no degradation of steviol (0.08
      and 0.2 mg/ml) appeared to be found during the incubation period. Stevia mixture,
      stevioside and rebaudioside A appeared to be hydrolyzed to steviol by human
      intestinal microflora: this observation is consistent with previous rat
      metabolism studies. Similarly, enzymatically modified stevia appeared to be
      metabolized via stevia components and, finally, to steviol. This study suggests
      that there are apparently no species differences in intestinal metabolism of
      stevia mixture between rats and humans.

PMID- 12504169
TI  - Cadmium, copper and nickel levels in vegetables from industrial and residential
      areas of Lagos City, Nigeria.
AB  - The levels of cadmium, copper and nickel in five different edible vegetables,
      Talinum triangulare, Celosia trigyna, Corchorus olitorus, Venomia amygydalina and
      Telfaria accidentalis, and the soils in which they were grown, from three
      industrial and three residential areas of Lagos City, Nigeria, were determined
      using atomic absorption spectrophotometry. The results obtained for these three
      heavy metals from the industrial areas were higher than those of the residential
      areas as a result of pollution. Industrial area results for vegetables ranged
      between 1.13 and 1.67 microg/g for cadmium; 25.08 and 56.84 microg/g for copper
      and 1.33 and 2.06 microg/g for nickel. There were statistically significant
      differences (P<0.05) between the levels of copper and nickel in all the
      vegetables studied from industrial and residential areas, while there was no
      statistically significant difference for cadmium. The results also show that
      Corchorus olitorus (bush okra) has the ability to accumulate more copper and
      nickel than the other vegetable studied but has the least ability to accumulate
      cadmium.

PMID- 12504170
TI  - Effects of combined exposure to lead and cadmium on the hypothalamic-pituitary
      axis function in proestrous rats.
AB  - The effects of lead and cadmium on the hypothalamic-pituitary axis were studied
      in proestrous rats. Adult female rats were treated intraperitonially with either
      lead acetate and cadmium acetate alone or in combination at a dose of 0.05 mg/kg
      daily for 15 days. Serotonin (5-HT) and norepinephrine (NE) levels decreased in
      individually and combined metal treated groups whereas dopamine (DA) levels were
      decreased only in the cadmium-exposed group. The pituitary levels of luteinizing
      hormone (LH) and follicle stimulating hormone (FSH) were decreased significantly
      in cadmium and combined treatment groups. In contrast, lead exposure failed to
      cause any change in serum LH and FSH levels, whereas cadmium and combined
      treatments showed significant decrease in serum LH and FSH levels as compared
      with control. The accumulation of both metals increased in the hypothalamus and
      pituitary after treatment. These data suggest that the metal accumulation
      disrupts the regulatory mechanisms of the hypothalamic-pituitary axis where the
      effects produced by the combined treatment of metals are not additive.

PMID- 12504171
TI  - Cytotoxic effects of the herbicide 2,4-dichlorophenoxyacetic acid in HepG2 cells.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely
      used to control the growth of broadleaf and woody plants. Although 2,4-D is well
      known to be moderately toxic, little information is available on the mechanisms
      of its toxicity. Results on carcinogenicity, genotoxicity and mutagenicity are
      contradictory, but neurotoxic, immunosuppressive and hepatotoxic effects have
      been defined. The aim of the present study was to investigate the cytotoxic
      effects of 2,4-D on a human hepatoma cell line. HepG2 cells were treated with
      different concentrations of 2,4-D, and cell viability, induction of
      apoptosis/necrosis and cell cycle phases were determined. Apoptosis was detected
      in flow cytometric light scatter histograms, the annexin V assay, the
      determination of DNA strand breaks with the TUNEL assay and the occurrence of a
      sub G(0) peak after propidium iodide (PI) staining. The induction of apoptosis by
      2,4-D was accompanied by a disruption of the mitochondrial membrane potential as
      verified by staining with the cationic JC-1 probe. In addition, 2,4-D affected
      the cell cycle in a concentration-dependent manner. Our investigation suggested
      that 2,4-D exerts its cytotoxic effects by the induction of apoptosis via a
      direct effect on the mitochondrial membrane potential.

PMID- 12504172
TI  - Cytotoxic response of Aspergillus fumigatus-produced mycotoxins on growth medium,
      maize and commercial animal feed substrates.
AB  - The occurrence of mycotoxin-producing moulds in animal feed is a severe problem
      since the quality of the feed is reduced and thereby both animal and human health
      can be affected. Aspergillus fumigatus is a common fungus found in improperly
      stored animal feed and the abundance of spores of the fungus is frequently spread
      into the air, exposing individuals who stay in areas where the fungus develops.
      The cytotoxic activities of extracts from three different A. fumigatus-inoculated
      substrates: (i) CzDox-broth; (ii) maize; and (iii) commercial feed grain as well
      as from gliotoxin, a mycotoxin produced by A. fumigatus, were studied in vitro
      using human neuroblastoma (SH-SY5Y) cells. Extracts of cultures from the
      gliotoxin-producing strain of A. fumigatus possessed cytotoxic activity in the
      cell system. Pure gliotoxin caused a 20% reduction of total protein content
      (EC(20)) at 0.12+/-0.02 microM, but also a 20% reduction in the number of
      neurites per cell body as compared with control cells (ND(20)) at 0.06+/-0.01
      microM. The results show that use of the SH-SY5Y cell model is a promising
      approach for detecting toxic activity in animal feed. Furthermore, the neurite
      degeneration of gliotoxin has to be investigated for estimation of a potentially
      neurotoxic risk.

PMID- 12504173
TI  - Evaluation of the toxicity of polyvinylacetate phthalate in experimental animals.
AB  - Polyvinylacetate phthalate (PVAP) is used in the pharmaceutical industry as an
      ingredient in coating systems for oral solid dosage forms and in inks for
      monogramming capsules. PVAP has been evaluated in both sexes of several species
      in a number of toxicological studies including acute, repeated dosing,
      subchronic, chronic and reproductive and developmental. The acute oral toxicity
      is low in rats and mice (LD(50) > 8000 mg/kg body weight), although it appears to
      be more toxic in the dog. The gastrointestinal tract appears to be the target
      organ and effects seen (irritation, laxation, colitis with erosions and
      submucosal fibrosis in the dog and ulcers, polyps, and cecal wall thickening in
      rats) were dose dependent. There were no consistent treatment-related adverse
      effects on reproductive performance or development (not teratogenic). The no
      observed-adverse-effect levels (NOAELs) ranged from 100 mg/kg body weight/day in
      the rabbit developmental toxicity study, to 500 mg/kg body weight/day in 24 month
      rat and dog studies, to 1000 mg/kg body weight/day in a one-generation
      reproduction study in the rat.

PMID- 12504174
TI  - Developmental toxicities of ethylbenzene, ortho-, meta-, para-xylene and
      technical xylene in rats following inhalation exposure.
AB  - The developmental toxicities of ethylbenzene, o-, m-, p-xylene and technical
      xylene were studied in Sprague-Dawley rats after inhalation exposure. Animals
      were exposed to either of these agents at 100, 500, 1000 or 2000 ppm, for 6
      h/day, during days 6-20 of gestation. All the agents tested caused maternal
      toxicity expressed as a reduction in maternal body weight gain at 1000 and 2000
      ppm. Decreased corrected weight gain and food consumption were observed at 1000
      and 2000 ppm ethylbenzene, o-, m- or p-xylene, and at 2000 ppm technical xylene.
      No evidence of teratogenic effects was found after exposure to any of these
      agents up to 2000 ppm. Fetal toxicity evidenced by significant decreases in fetal
      body weights occurred at concentrations of 500 ppm or greater of o-xylene or
      technical xylene, and 1000 ppm or greater of ethylbenzene, m- or p-xylene. A
      significant increase in the mean percentage of fetuses per litter with skeletal
      variations was also noted at 2000 ppm ethylbenzene, o- and p-xylene. In summary,
      all tested agents produced developmental toxicity at 1000 and 2000 ppm,
      concentrations that also produced significant maternal toxicity. With o-xylene
      and technical xylene, developmental toxicity also occurred at 500 ppm, in the
      absence of maternal toxic effects. However, the only indication of a treatment
      related effect was a slight decrease in fetal weight.

PMID- 12504175
TI  - Effect of pretreatment of cytochrome P450 (P450) modifiers on neurobehavioral
      toxicity induced by deltamethrin.
AB  - To investigate the involvement of cytochrome P450 (P450) enzyme induction and the
      effect of different P450 modifiers in the neurobehavioral toxicity of
      deltamethrin, deltamethrin (10 mg/kg; orally for 1 day) was administered to young
      male albino Wistar rats, or in rats pretreated with phenobarbital (PB; 80 mg/kg,
      ip for 5 days), an inducer of P450 2B1/2B2 or 3-methylcholanthrene (MC; 30 mg/kg,
      ip for 5 days), an inducer of P450 1A1/1A2 or cobalt chloride (CoCl(2); sc for 2
      days), a depletor of P450s. The administration of PB or MC or CoCl(2) alone did
      not produced any symptoms of neurobehavioral toxicity. While a single oral
      administration of deltamethrin produced tremors in two out of 10 rats and
      decreased the spontaneous locomotor activity, pretreatment with MC or PB
      potentiated the deltamethrin induced neurobehavioral toxicity with 50% of the
      treated rats exhibiting tremors. Half of the animals pretreated with MC prior to
      exposure to deltamethrin also exhibited choreoathetosis. The decrease in the
      spontaneous locomotor activity was found to be much more significant in PB- or MC
      pretreated animals exposed to deltamethrin. In contrast to the pretreatment with
      inducers, rats pretreated with CoCl(2) exhibited no symptoms of tremors or
      choreoathetosis, indicating that a reactive metabolite of deltamethrin is formed
      by P450 catalysed reactions which is involved in the neurobehavioral toxicity of
      deltamethrin.

PMID- 12504176
TI  - Investigation of the adjuvant and immuno-suppressive effects of benzyl butyl
      phthalate, phthalic acid and benzyl alcohol in a murine injection model.
AB  - In a recent study, di-(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono-2
      ethylhexyl phthalate, were shown to possess adjuvant effect [Toxicology 169
      (2001) 37; Toxicology Letters 125 (2001) 11]. The present study investigates the
      adjuvant effect of another important commercial phthalate plasticizer, benzyl
      butyl phthalate (BBP) as well as its degradation products, phthalic acid and
      benzyl alcohol (BA) in a murine model. The model antigen, ovalbumin (OA), was
      injected either alone (OA control group), together with one of the test
      substances (test group) or together with aluminium hydroxide, which served as the
      positive adjuvant control. The mice were boosted either once or twice with OA
      before blood was collected and assayed for the content of OA-specific IgE, IgG1
      and IgG2a antibodies by ELISA methods. Adjuvant effect was defined as a
      statistically significant increased antibody level in the test groups compared
      with the OA control group. Conversely, if the antibody production in a test group
      was significantly lower than the OA control group, it was deemed to be
      immunosuppression. This study demonstrated that BBP, in contrast to DEHP, did not
      possess adjuvant effect. Furthermore, immunosuppression was apparent in the case
      of BA. The study also demonstrated that if the injections give rise to formation
      of wounds, it may cause false positive results.

PMID- 12504177
TI  - Determination of trenbolone and its metabolite in bovine fluids by liquid
      chromatography-tandem mass spectrometry.
AB  - A liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method has been
      developed for the determination of trenbolone in bovine urine and serum. The aim
      was a control of the misuse of trenbolone in food-producing animals. The
      procedure involved, in both cases, a preliminary solid-phase clean-up followed by
      a liquid-liquid extraction for urine samples after a preliminary enzymatic
      hydrolysis. The extracts have been directly analysed by reversed-phase LC-MS-MS
      in selected reaction monitoring (SRM), acquiring two diagnostic product ions from
      the chosen precursor [M+H](+). The procedures were validated across the
      concentration range of 1-1500 ng/ml. The linearity, the inter- and intra-day
      accuracy and precision have been determined. The procedure was specific and the
      accuracy values were better than 20% at the limit of quantitation of spiked
      samples. The limit of quantification (LOQ) and the limit of detection (LOD) were,
      respectively, 1 ng/ml and 350 pg/ml for urine and serum. According to the draft,
      SANCO/1805/2000, we determined the decision limit CCalpha and the detection
      capability CCbeta. The recovery values for urine ranged from 87 to 128%, and for
      plasma the recovery was 70+/-4%. The procedure proved to be simple and suitable
      for routine and confirmatory purposes such as those developed for residue
      studies.

PMID- 12504178
TI  - Determination of cefaclor in human plasma by a sensitive and specific liquid
      chromatographic-tandem mass spectrometric method.
AB  - A sensitive and specific liquid chromatographic-tandem mass spectrometric method
      is described for the determination of cefaclor in human plasma. The plasma
      samples were treated by two sample preparation procedures, i.e. protein
      precipitation (PPT) and solid-phase extraction (SPE). The pretreated samples were
      analyzed on a C(18) HPLC column interfaced with a triple quadrupole tandem mass
      spectrometer. Positive electrospray ionization (ESI) was employed as the
      ionization source. The analyte and internal standard ampicillin (for PPT) or
      cefetamet (for SPE) were detected by use of selected reaction monitoring (SRM)
      mode. The lower limit of quantitation obtained as a result of the PPT procedure
      was 100 ng/ml. The intra- and inter-run precision, calculated from quality
      control (QC) samples was less than 12% for cefaclor. The accuracy as determined
      from QC samples was within +/-3% for the analyte. The SPE procedure could provide
      the lower limit of quantitation of 2 ng/ml. The precision and accuracy were
      measured to be below 7.1% and between -3.6% and 1.1%, respectively, for all QC
      samples. The method was applied for the evaluation of the pharmacokinetic
      profiles of cefaclor sustained-release formulation.

PMID- 12504179
TI  - Simple and sensitive determination of the new antitumor drug CKD-602 in human
      plasma by liquid chromatography.
AB  - A simple and sensitive high-performance liquid chromatographic with fluorescence
      detection method has been developed and validated for the determination of the
      new antitumor agent CKD-602 in human plasma. Plasma proteins were precipitated
      with methanol and the samples were acidified with 7% (v/v) perchloric acid. The
      supernatants were analyzed by HPLC using a Capcell Pak C(18) UG120 column and a
      mixture of methanol-0.1 M hexane-1-sulfonic acid in methanol-0.01 M TEMED in
      water at pH 6.0 (40:1:59, v/v) as the mobile phase. The lower limit of
      quantification was 0.2 ng/ml using 200 microliter plasma samples. Mean within-run
      precision and between-run precision at six tested concentrations (0.2-400 ng/ml)
      were </=10% and mean accuracy was </=15%. Stability studies showed that CKD-602
      is stable in both plasma and methanol extracts for at least 3 months at -30
      degrees C. The described method was used for the pharmacokinetic analysis of CKD
      602 during clinical phase I studies, in patients with solid tumors.

PMID- 12504180
TI  - One step purification of alpha(1)-acid glycoprotein from human plasma.
      Fractionation of its polymorphic allele products.
AB  - Alpha(1)-acid glycoprotein is a plasma protein that exhibits both
      microheterogeneity and polymorphism. Its purification from human plasma is
      usually performed using a sequence of different fractionation steps. Here we
      report a one-step isolation technique of this protein based upon pseudo-ligand
      affinity chromatography on immobilized Cibacron Blue F3GA at acidic pH. In
      addition, the use of two narrow pH elution buffers allows us to separate the two
      genetic products of this protein, which differ from each other by 21 amino acid
      substitutions. This technique will facilitate the study of the structural,
      biological and pharmacokinetic properties of each individual allele product.

PMID- 12504181
TI  - Determination of prednisolone and the most important associated compounds in
      ocular and cutaneous pharmaceutical preparations by micellar electrokinetic
      capillary chromatography.
AB  - A micellar electrokinetic capillary chromatographic method to separate
      prednisolone, prednisolone acetate, naphazoline, Zn-bacitracin, sulfacetamide and
      phenylefrine is described. The separation was carried out by using a fused-silica
      capillary (57 cmx75 micrometer I.D.) at 25 degrees C and 30 kV, using a 5 mM
      phosphate-5 mM borate buffer adjusted to pH 8.2, 50 mM sodium dodecyl sulfate
      (SDS) and 10% methanol-water (v/v) as background electrolyte. Under these
      conditions, the run time was 8 min and the limits of quantification were about
      1.0 mg/l for every component. The method was applied to pharmaceutical
      preparations and the results provided recoveries close to 100% and the method
      gave good results when compared with a reference multivariate calibration
      spectrophotometric method.

PMID- 12504182
TI  - Determination of testosterone metabolites in human hepatocytes. I. Development of
      an on-line sample preparation liquid chromatography technique and mass
      spectroscopic detection of 6beta-hydroxytestosterone.
AB  - A rapid and sensitive RP-HPLC assay for determination of 6beta
      hydroxytestosterone in human hepatocytes with corticosterone as the internal
      standard is described. The procedure employs on-line sample enrichment using a
      BioTrap 500 MS (20x4 mm I.D.) extraction pre-column and subsequent gradient
      separation on a Prontosil 60-5 C(18)-H (250x2 mm I.D., 5 micrometer particle
      size) analytical column in the back-flush mode using a ternary eluent system
      composed of methanol, tetrahydrofuran and water. Signal monitoring was done by
      measurement of the responses from liquid chromatography coupled to mass
      spectroscopy (LC-MS/MS) using an atmospheric pressure chemical ionization (APCI)
      source conducted in the selected reaction monitoring (SRM) mode. Mean recoveries
      of 6beta-hydroxytestosterone from an estimate of the biological matrix, i.e.,
      Dulbecco's modified Eagle medium "High Glucose", ranged from 101.8-104.4% for
      samples containing the target analyte at the 250, 500 and 1000 ng/ml level. The
      limit of quantitation (LOQ) was 20 ng/ml at an injection volume of 100 microliter
      determined in the same matrix. Linearity of signal responses versus concentration
      for all three analytes was accomplished in the range of 100-4000 ng/ml. Mean
      values of the coefficients of variation (C.V.) for the target analyte obtained
      for the concentrations 250, 500 and 1000 ng/ml at 5 different days in
      quintuplicate ranged from 1.5-7.7% (within-day) and 4.8-7.3% (between-day). The
      corresponding values for the accuracy ranged from 87.7-106.1% for the within-day
      and from 98.8-102.5% for the between-day measurements. The target analyte was
      sufficiently stable at both storage and sample preparation conditions because no
      substantial deviations between analyte concentrations measured before and after
      subsequently performed freeze and thaw cycles were observed.

PMID- 12504183
TI  - Determination of cortisol in human saliva using liquid chromatography
      electrospray tandem mass spectrometry.
AB  - The aim of this work was to develop a method for determination of cortisol in
      saliva by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Saliva was
      sampled on Salivette tubes. These were centrifuged, deuterium-labeled cortisol
      was added as internal standard and the proteins precipitated by acetonitrile. The
      supernatant was evaporated, dissolved in methanol acidified with acetic acid and
      analyzed by LC-MS-MS. The with-in run precision, tested by pooling saliva samples
      from volunteers and then analyzing these in a single run, was found to be 7% at
      0.7 microgram l(-1). The between-run precision was tested by analysis of the same
      samples at different days and found to be 11% at 2.5 microgram l(-1). The limit
      of quantification was 0.5 microgram l(-1). The method was applied for analysis of
      saliva samples from three volunteers during their last week before vacation and
      the first and second week on vacation. In addition, the method was compared to
      analysis by an immunological method. The values from the immunological method
      were 2.7 times higher than the LC-MS-MS results.

PMID- 12504184
TI  - Synthesis of [(18)O(2)]valproic acid and its use as an internal standard for the
      quantitative measurement by gas chromatography-electron ionization mass
      spectrometry.
AB  - A specific method for the quantitative determination of valproic acid in human
      plasma is presented. Valproate was extracted from acidified plasma by hexane
      extraction and converted to its trimethylsilyl derivative without sample
      concentration. The derivatives were analyzed without any further purification.
      Using gas chromatography-electron ionization mass spectrometry, diagnostic useful
      fragment ions at m/z 201 and 205 were obtained for valproic acid and
      [(18)O(2)]valproic acid internal standard, respectively. [(18)O(2)]Valproic acid
      was synthesized from unlabeled valproate by acid-catalyzed exchange reaction in
      H(2)(18)O. The method was validated in the expected concentration range of a
      pharmacokinetic study. Thus, calibration graphs were linear within a range of
      0.47-120 microgram/ml plasma. Intra-day precision was 2.29% (0.47 microgram/ml),
      2.93% (4 microgram/ml), 3.22% (20 microgram/ml) and 4.40% (80 microgram/ml),
      inter-day variability was found to be 1.49% (0.47 microgram/ml), 3.79% (20
      microgram/ml), 2.74% (40 microgram/ml) and 3.03% (80 microgram/ml). Inter-day
      accuracy showed deviations of 1.94% (0.47 microgram/ml), 0.53% (4 microgram/ml), 
      0.32% (20 microgram/ml) and 0.06% (80 microgram/ml). The method is rugged and
      robust and has been applied to the batch analysis of valproate during
      pharmacokinetic profiling of the drug.

PMID- 12504185
TI  - Accurate quantification of basal plasma levels of 3-nitrotyrosine and 3
      nitrotyrosinoalbumin by gas chromatography-tandem mass spectrometry.
AB  - Measurement of 3-nitro-L-tyrosine (NO(2)Tyr) and protein-related 3-nitro-L
      tyrosine in human plasma is associated with numerous methodological problems
      which result in highly divergent basal plasma levels often ranging within two
      orders of magnitude. Recently, we have described an interference-free GC-tandem
      MS-based method for NO(2)Tyr which yielded the lowest basal plasma NO(2)Tyr
      levels reported thus far. This method was extended to quantify protein-associated
      3-nitrotyrosine and in particular 3-nitrotyrosinated albumin (NO(2)TyrALB) in
      human plasma. NO(2)TyrALB and albumin (ALB) were extracted from plasma by
      affinity column extraction and digested enzymatically at neutral pH. 3-Nitro- L
      [2H(3)]tyrosine was used as internal standard. In plasma of 18 healthy young
      volunteers the molar ratio of NO(2)TyrALB to albumin-derived tyrosine (TyrALB),
      i.e. NO(2)TyrALB/TyrALB, was determined to be 1.55+/-0.54x1:10(6) (mean+/-SD).
      The plasma concentration of NO(2)TyrALB was estimated as 24+/-4 nM. The NO(2)Tyr
      plasma levels in these volunteers were determined to be 0.73+/-0.53 nM. In the
      same volunteers, NO(2)TyrALB/TyrALB, NO(2)TyrALB and NO(2)Tyr were measured 15
      days later and the corresponding values were determined to be 1.25+/
      0.58x1:10(6), 25+/-6 nM and 0.69+/-0.16 nM. For comparison, NO(2)Tyr and
      NO(2)TyrALB were measured in six plasma samples from healthy volunteers by GC-MS
      and GC-tandem MS. Different values were found for NO(2)Tyr, i.e. 5.4+/-2.8 versus
      2.7+/-1.5 nM, and comparable values for NO(2)TyrALB/TyrALB, i.e. 0.5+/
      0.2x1:10(6) versus 0.4+/-0.1x1:10(6), by these methods. The ratio of the values
      measured by GC-MS to those measured by GC-tandem MS were 2.9+/-3.1 for NO(2)Tyr
      and 1.2+/-0.2 for NO(2)TyrALB/TyrALB. The present GC-tandem MS method provides
      accurate values of NO(2)Tyr and NO(2)TyrALB in human plasma.

PMID- 12504186
TI  - Development and validation of a bioanalytical method for the determination of the
      cholecystokinin type-1 (CCK(1)) receptor antagonist dexloxiglumide in human
      plasma.
AB  - A sensitive bioanalytical method for the measurement of dexloxiglumide, a new
      selective and potent cholecystokinin type-1 (CCK(1)) receptor antagonist, in
      plasma, is reported. The method is based on reversed-phase liquid chromatography
      with ultraviolet absorption detection. Samples are extracted under acidic
      conditions into an organic solvent, and following evaporation, reconstitution and
      centrifugation stages, the supernatant is injected on to an ODS column with
      detection at 244 nm. The method has been validated over the concentration range
      0.2-20 microgram/ml, 0.2 microgram/ml being the lower limit of quantification.
      The overall precision and accuracy (expressed as relative error) of the method
      was less than 6.1 and 2.3%, respectively. Dexloxigulmide was shown to be stable
      in plasma when stored at -20 degrees C for at least 200 days. The method is
      suitable for studying the pharmacokinetics of dexloxiglumide in man.

PMID- 12504187
TI  - Analysis of intracellular nucleoside triphosphate levels in normal and tumor cell
      lines by high-performance liquid chromatography.
AB  - A reversed-phase ion-pair high-performance liquid chromatographic method for the
      direct and simultaneous determination of ribonucleoside triphosphates and their
      corresponding deoxyribonucleoside triphosphates in trichloroacetic acid cell
      extracts is presented. Using this system, high resolution of nine acid-soluble
      compounds, including ADP, CTP, dCTP, GTP, UTP, dGTP, dTTP, ATP and dATP in 16
      normal or tumor cell lines, is obtained. The method is based on an extraction of
      nucleotides from cells with a solution of 6% trichloroacetic acid followed by
      neutralization with the addition of 5 M K(2)CO(3) just prior to HPLC analysis.
      Chromatographic separations were performed using a Symmetry C(18) 3.5 micrometer
      (150x4.6 mm) column (Waters) equipped with a NovaPak C(18) Sentry guard column
      with UV detection at 254 nm. The HPLC columns were kept at 27 degrees C. The
      mobile phase was delivered at a flow-rate of 1.0 ml/min, with the following
      stepwise gradient elution program: A-B (60:40) at 0 min-->(40:60) at 30 min-
      >(40:60) at 60 min. Solvent A contained 10 mM tetrabutylammonium hydroxide, 10 mM
      KH(2)PO(4) and 0.25% MeOH, and was adjusted to pH 6.9 with 1 M HCl. Solvent B
      consisted of 5.6 mM tetrabutylammonium hydroxide, 50 mM KH(2)PO(4) and 30% MeOH,
      and was neutralized to pH 7.0 with 1 M NaOH. The calibration curves (r>0.99) of
      the components in cell extracts were established with their aqueous standards.
      The average within-day precision for the nine compounds was 0.9%, and the average
      day-to-day precision was 5.0%. The detection limits (pmol) of the nine reagents
      were 1.39 (ADP), 4.32 (CTP), 15.5 (dCTP), 2.38 (GTP), 4.42 (UTP), 9.45 (dGTP),
      14.6 (dTTP), 2.44 (ATP) and 11.8 (dATP). The recovery of this method for the
      standards ranged from 82.4 to 120.5%. The results for the detection of nucleotide
      pools in 16 normal and tumor cell lines were presented. In conclusion, this
      simplified analytical method enables the simultaneous quantitation of NTP and
      dNTP in cell or tissue extracts and may represent a valuable tool for the
      detection of minute alterations of intracellular NTP/dNTP pools induced by
      anticancer/antiviral drugs and diseases.

PMID- 12504188
TI  - Determination of 6-hydroxychlorzoxazone and chlorzoxazone in porcine microsome
      samples.
AB  - A simple, accurate and sensitive HPLC method for the in vitro determination of 6
      hydroxychlorzoxazone and chlorzoxazone in porcine microsome samples is described.
      Chromatography was performed on a YMC-Pack ODS-AQ column using a mobile phase of
      0.05% phosphoric acid pH 3-methanol (60:40, v/v). UV detection was carried out at
      287 nm. The detector response was linear over the concentration range 25-2000
      ng/ml. This assay produced quick, accurate, and repeatable results.

PMID- 12504189
TI  - Use of large particles support for fast analysis of methadone and its primary
      metabolite in human plasma by liquid chromatography-mass spectrometry.
AB  - A bioanalytical method was developed for the quantitation of methadone (MTD) and
      its primary metabolite, (EDDP) in plasma. The extraction step was performed
      within a capillary column packed with large particles (35x0.3 mm I.D.; d(p) 30
      micrometer) at high flow-rate conditions (450 microliter/min). The separation was
      performed on a microbore analytical column (55x2 mm I.D.; d(p) 3 micrometer)
      coupled to a mass spectrometer (MS). This procedure was based on a column
      switching unit. Analytes of interest were retained on the precolumn by
      hydrophobic interactions and backflushed from the precolumn to the analytical
      column. The detection was carried out with a MS single quadrupole equipped with
      an electrospray interface. The total analysis time was 6 min. The limits of
      quantification were evaluated at 10 and 25 ng/ml for MTD and EDDP, respectively.
      At this level, good accuracies were obtained for both analytes with repeatability
      values less than 18%.

PMID- 12504190
TI  - Determination of diaminopimelic acid in rat feces by high-performance liquid
      chromatography using the Pico Tag method.
AB  - The purpose of the study was to develop a method for the determination of
      diaminopimelic acid (DAPA) concentrations in rat feces by reversed-phase high
      performance liquid chromatography (HPLC) using the Pico Tag method. Precolumn
      derivatization with phenylisothyocyanate (PITC) and UV (254 nm filter) detection
      were used. Samples were hydrolysed in 6 M HCl at 110 degrees C for 24 h.
      Hydrolysates were then diluted, dried and derivatized, and samples (10 microliter
      injected onto a 300x3.9 mm NovaPak C(18) (Waters) HPLC column. Under the
      conditions used, DAPA eluted as one single peak between those of tyrosine and
      valine. On-column DAPA concentrations in standards were 41.5-83 pmol, which were
      in the range of the amounts present in fecal samples of rats fed semisynthetic
      diets. Amounts of DAPA determined in fecal samples of rats fed broad bean- or
      chickpea-based diets were, respectively, 2.56 and 2.98 mg g(-1). The advantages
      of the method and the relevance of the results for nutritional studies in
      monogastric animals are discussed.

PMID- 12504191
TI  - Effect of different sample pretreatment methods on the concentrations of
      excitatory amino acids in cerebrospinal fluid determined by high-performance
      liquid chromatography.
AB  - Using high-performance liquid chromatography (HPLC), the effect of different
      sample pretreatment methods on the concentrations of excitatory amino acids
      (EAAs, glutamate and aspartate) measured in cerebrospinal fluid (CSF) was
      investigated. The results showed that the measured values of glutamate and
      aspartate were constant when the samples were stored at -80 degrees C and then
      methanol was used for CSF deproteinization before assay; the values of glutamate
      (Glu) increased when 0.3 M perchloric acid was used for CSF deproteinization with
      the CSF subsequently being stored at -20 degrees C; the values of Glu changed
      when the samples were stored at -20 degrees C over 8 weeks with methanol
      subsequently being used for CSF deproteinization before assay. This reference
      data suggested that the CSF sample would be better stored at -80 degrees C. If
      the sample is stored at -20 degrees C over 8 weeks, the Glu values change with
      the storage time. If strong acidic reagents are used for precipitation of protein
      in the CSF sample and then stored at -20 degrees C, Glu values are abnormally
      increased. From this study, an accurate and sensitive reversed-phase high
      performance liquid chromatographic method has been developed for anti
      excitotoxicity therapy and thorough study of EAAs in a clinical setting.

PMID- 12504192
TI  - Quantitation of soy-derived phytoestrogens in human breast tissue and biological
      fluids by high-performance liquid chromatography.
AB  - A new and reliable HPLC method for the quantitation of daidzein, equol, and
      genistein in human breast tissue has been developed. The method was applied to
      biopsies from women undergoing breast reductions, who, prior to surgery, had
      ingested either a soy isoflavone preparation or a placebo tablet. The results
      were compared with data collected for urine and serum of the same subjects using
      standard methods. The limits of detection in the breast tissue homogenate were
      24.7 nmol/l for daidzein, 148.0 nmol/l for equol, and 28.4 nmol/l for genistein
      (S/N of 3). The chromatographic limits of quantitation were 62.5 nmol/l for
      daidzein and genistein, and 125.0 nmol/l for equol, for which the accuracies were
      86.0%, 83.6%, and 81.8%, respectively. The coefficients of variation of these
      measurements were all below 20% (11.1% for daidzein, 16.4% for genistein, and
      13.2% for equol). The sample preparation comprised a concentration step and the
      absolute limits of quantitation were, therefore, 4.7 nmol/l, 18.8 nmol/l, and
      0.94 nmol/l for daidzein and genistein, and 9.4 nmol/l, 37.5 nmol/l, and 1.9
      nmol/l for equol in urine, serum, and breast tissue homogenate, respectively.
      Recoveries were between 70% (+/-5.6%) in breast tissue homogenate and 100% (+/
      14.1%) in urine and serum for all three compounds. Equol (less than 1 micromol/l
      homogenate) was found to be the predominant phytoestrogen in breast tissue and
      its concentrations exceeded those in serum. The concentrations of phytoestrogens
      were at least 100-fold higher in urine than in serum and breast tissue.

PMID- 12504193
TI  - Gas chromatographic method for detection of urinary sucralose: application to the
      assessment of intestinal permeability.
AB  - We developed a capillary column gas chromatography (CCGC) method for the
      measurement of urinary sucralose (S) and three other sugar probes including,
      sucrose, lactulose (L) and mannitol (M) for use in in vivo studies of intestinal
      permeability. We compared the capillary method with a packed column gas
      chromatography (PCGC) method. We also investigated a possible role for sucralose
      as a probe for the measurement of whole gut permeability. Sample preparation was
      rapid and simple. The above four sugars were detected precisely, without
      interference. We measured intestinal permeability using 5- and 24-h urine
      collections in 14 healthy volunteers. The metabolism of sugars was evaluated by
      incubating the intestinal bacteria with an iso-osmolar mixture of mannitol,
      lactulose and sucralose at 37 degrees C for 19 h. Sugar concentrations and the pH
      of the mixture were monitored. The use of the CCGC method improved the detection
      of sucralose as compared to PCGC. The average coefficient of variation decreased
      from 15% to 4%. It also increased the sensitivity of detection by 200-2000-fold.
      The GC assay was linear between sucralose concentrations of 0.2 and 40 g/l
      (r=1.000). Intestinal bacteria metabolized lactulose and acidified the media but
      did not metabolize sucralose or mannitol. The new method for the measurement of
      urinary sucralose permits the simultaneous quantitation of sucrose, mannitol and
      lactulose, and is rapid, simple, sensitive, accurate and reproducible. Because
      neither S nor M is metabolized by intestinal bacteria, and because only a tiny
      fraction of either sugar is absorbed, this pair of sugar probes appears to be
      available for absorption throughout the GI tract. Thus, the 24-h urinary
      concentrations of S and M, or the urinary S/M ratio following an oral dose of a
      sugar mixture, might be good markers for whole gut permeability.

PMID- 12504194
TI  - Isolation and identification of two [(3)H]norharman- ([(3)H]beta-carboline)
      binding proteins from rat liver.
AB  - Norharman (9H-pyrido-[3,4-b]indol) represents a member of the mammalian alkaloids
      with the group name beta-carbolines. In mammals, it exhibits psychotropic and co
      mutagenic actions. Highly specific [(3)H]norharman binding sites have been
      detected in the liver of rats (B(max): 11 pmol mg(-1) protein; K(D): lower
      nanomolar range). Two [(3)H]norharman binding proteins with apparent molecular
      masses of 60 and 80 kDa (SDS-PAGE) were isolated from rat liver crude membrane
      fraction and identified as the enzyme carboxylesterase (EC 3.1.1.1; 60 kDa) and
      the stress protein glucose-regulated protein 78 (GRP78; 78 kDa). Possible
      functional consequences of the interaction of norharman with these two proteins
      are discussed.

PMID- 12504195
TI  - On-line clean-up by multidimensional liquid chromatography-electrospray
      ionization tandem mass spectrometry for high throughput quantification of primary
      and secondary phthalate metabolites in human urine.
AB  - We developed a new and fast multidimensional on-line HPLC-method for the
      quantitative determination of the secondary, chain oxidized monoester metabolites
      of diethylhexylphthalate (DEHP), 5-hydroxy-mono-(2-ethylhexyl)-phthalate (5OH
      MEHP) and 5-oxo-mono-(2-ethylhexyl)-phthalate (5oxo-MEHP) in urine samples from
      the general population. Also included in the method were the simple monoester
      metabolites of DEHP, dioctylphthalate (DOP), dibutylphthalate (DBP),
      butylbenzylphthalate (BBzP) and diethylphthalate (DEP). Except for enzymatic
      hydrolysis for deconjugation of the metabolites no further sample pre-treatment
      step is necessary. The phthalate metabolites are stripped from urinary matrix by
      on-line extraction on a restricted access material (LiChrospher((R)) ADS-8)
      precolumn, transferred in backflush-mode and chromatographically resolved by
      reversed-phase HPLC. Eluting metabolites are detected by ESI-tandem mass
      spectrometry in negative ionization mode and quantified by isotope dilution.
      Within a total run time of 25 min we can selectively and sensitively quantify
      seven urinary metabolites of six commonly occurring phthalate diesters including
      the controversial di(2-ethylhexyl)phthalate (DEHP). The detection limits for all
      analytes are in the low ppb range (0.5-2.0 microgram/l urine). First results on a
      small non-exposed group (n=8) ranged for 5OH-MEHP from 0.59 to 124 microgram/l,
      for 5oxo-MEHP from <LOQ to 73.0 microgram/l, and for MEHP from <LOQ to 41.1
      microgram/l. The other short chain monoester metabolites were detectable in every
      sample with mean concentrations for MnBuP of 36.5 microgram/l, for MBzP of 7.19
      microgram/l and MEP of 1.0 mg/l. With this rapid and economic method we can
      determine the internal exposure of the general population to DEHP and other
      phthalates as well as the body burden of occupationally and medically exposed
      subjects. The results can help to rank the risks of phthalates in the areas of
      carcinogenesis, peroxisome proliferation and endocrine disruption. Since
      secondary, functionalized metabolites of DEHP are included in the method an
      enduring problem of the past is excluded: sample contamination in the pre
      analytical and analytical phase by both di- and monoesters.

PMID- 12504196
TI  - Expanded bed adsorption processing of mammalian cell culture fluid: comparison
      with packed bed affinity chromatography.
AB  - A comparison between expanded bed adsorption and conventional packed bed Protein
      A Fast Flow to purify the anti-rHBsAg mAbs from feedstock is presented in this
      work. Direct capture by STREAMLINE expanded bed adsorption chromatography
      resulted in 92% product recovery and sevenfold more concentrated product with
      similar purity levels compared to that obtained by the standard packed method.
      The process time and buffer consumption were reduced in the expanded bed
      adsorption method not only with the binding-elution conditions but also with the
      use of NaOH during the cleaning-in-place step. The latter is the most widely
      accepted agent in downstream processing, being a cost effective technique that
      provides not only efficient cleaning but also sanitizes complete column systems
      and destroys pirogens.

PMID- 12504197
TI  - Liquid chromatography method for the analysis of adenosine compounds.
AB  - A newly available chromatography column packing material that employs hybrid
      particle technology was used to improve the analysis of adenosine compounds.
      Using a TBAS buffer/acetonitrile gradient this material permits separation of
      etheno-adenosine compounds in less than 4 min with excellent resolution and
      sensitivity (50 fmol). Variability of compound quantification is small
      (coefficients of variation 0.23+/-0.14% for 50 pmol and 1.70+/-0.53% for 0.5
      pmol). The new method is well suited for the analysis of adenosine compounds in
      small biological samples and permits a high sample throughput in autosampler
      setups with high precision and reproducibility.

PMID- 12504198
TI  - Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma
      by liquid chromatography.
AB  - A simple, selective, sensitive and precise high-performance liquid
      chromatographic plasma assay for the antihypertensive drugs, irbesartan and
      hydrochlorothiazide is described. Good chromatographic separation was achieved
      using a Supelcocil C(18) (5 micrometer 15 cmx4.6 mm) column and a mobile phase
      consisting of 10 mM potassium dihydrogen phosphate:methanol:acetonitrile (5:80:15
      v/v/v) (pH:2.5) while at a flow-rate of 1.0 ml min(-1). Irbesartan and
      hydrochlorothiazide were detected at 275 nm and were eluted 5.8 and 7.8 min,
      respectively, after injection. No endogenous substances were found to interfere.
      The method utilizes protein precipitation with acetonitrile as the only sample
      preparation involved prior to reversed-phase high-performance liquid
      chromatography. No internal standard was required. Linearity range for irbesartan
      and hydrochlorothiazide was 10.0-60.0 microgram ml(-1) and 4.0-20.0 microgram ml(
      1), respectively. The determination of intra- and inter-day precision (RSD) was
      less than 2.5 and 3.5%, at all concentration levels, while the inter- and intra
      day accuracy (% difference) was less than 4.9-6.2%. This method is being used in
      a therapeutic drug monitoring service to quantitate these therapeutic agents in
      patients for pharmacokinetic studies.

PMID- 12504199
TI  - Improved lectin-mediated immobilization of human red blood cells in superporous
      agarose beads.
AB  - A new type of agarose bead, superporous agarose, was used as a gel support for
      immobilization of human red blood cells (RBCs) mediated by wheat germ lectin. The
      number of immobilized cells was similar to that obtained with commercial wheat
      germ lectin-agarose but the cell stability appeared to be superior. This allowed
      improved frontal affinity chromatographic analyses of cytochalasin B (CB)-binding
      to the glucose transporter GLUT1 which established a ratio of one CB-binding site
      per GLUT1 dimer for both plain RBCs or those treated with different poly amino
      acids. The measured dissociation constants, 70+/-14 nM for CB and 12+/-3 mM for
      glucose binding to GLUT1, are similar to those reported earlier.

PMID- 12504200
TI  - II. Perinatal brain tumors: a review of 250 cases.
AB  - Central nervous system tumors occur considerably less often in the fetus and
      neonate than in the older child. They are not entirely the same as those present
      later in life. Their location, biologic behavior, response to therapy, and
      histologic types are different. Fetal and neonatal brain tumors (n = 250) were
      collected from the literature and studied for this review. The overall survival
      rate was 28%. The entire cranial cavity may be filled with tumor, and stillbirth
      is not uncommon. Macrocephaly was the most frequent presentation regardless of
      histology. Outcome is related to the size and location of the tumor, the
      histologic type, surgical resectability, and the condition of the infant at the
      time of diagnosis. Neonates with choroid plexus papillomas, gangliogliomas, and
      low-grade astrocytomas have the best prognosis, whereas those with teratomas and
      primitive neuroectodermal tumors have the worst prognosis.

PMID- 12504201
TI  - Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females.
AB  - Aicardi syndrome is an X-linked-dominant condition characterized by infantile
      spasms, agenesis of the corpus callosum, and chorioretinal lacunae. We reviewed
      the Aicardi Syndrome Foundation's compilation of family-based, self-reported
      questionnaires for the year 2000. Information was obtained from 77 females with
      Aicardi syndrome regarding developmental milestones, seizure frequency, seizure
      classification, antiepileptic drug use, and medical problems. Patient ages ranged
      from 1 to 25 years (mean = 7.2 years). All patients were significantly
      developmentally delayed with milestones ranging from 2 to 36 months. Of the
      patients, 91% attained milestones no higher than 12 months. Seizures were
      reported in 92% of patients and occurred daily in 67%. Infantile spasms were the
      most common seizure type observed in 17%, although a variety of other seizure
      types were also reported. Multiple antiepileptic drugs were used in these
      patients with 73% of patients taking two or more antiepileptic drugs. Five
      patients had a vagal nerve stimulator implanted, and one patient underwent a
      hemispherectomy. The most common medical problems cited included scoliosis,
      constipation, gastroesophageal reflux, aspiration pneumonia, and otitis media,
      but overall health was perceived to be good. Our review demonstrates the spectrum
      of developmental disabilities, epilepsy severity, and prognosis in a large group
      of Aicardi patients.

PMID- 12504202
TI  - A comparison survey of seizures and other symptoms of Pokemon phenomenon.
AB  - On 16 December 1997, many Japanese children developed neurologic problems while
      watching the animated television series Pokemon. This study included children who
      visited the outpatient departments of 14 pediatric clinics for other reasons
      within 2 months after this incident. Volunteering children and parents or
      guardians were asked to complete questionnaires. We obtained 1,373 replies
      (including 800 males, 558 females, and 15 children without information on sex;
      mean age, 6.8 +/- 3.5 years). The majority of children included in this study
      (80%) watched this program, and 67 (6.1%; 40 males, 27 females) were affected by
      the program. There were 10 patients with seizures (0.9%; four males and six
      females). Fifty-seven patients developed other symptoms. Compared with
      nonaffected children, significantly more affected children reported that they
      concentrated on watching this program, watched it at a short distance from the
      screen, and did not watch this program in a brightly lit room. Seizures tended to
      occur in older children (average = 10.8 years) and in children with a high rate
      of familial histories of seizures. Symptoms other than seizures occurred more
      frequently, and autonomic and psychologic factors, such as motion sickness, could
      be considered possible mechanisms. Children who developed symptoms seemed to have
      problems in viewing conditions.

PMID- 12504203
TI  - Cerebral lateralization and cognitive deficits after congenital hemiparesis.
AB  - The purpose of this study was to investigate whether and how handedness is
      related to the processes of cerebral lateralization and cognitive performance in
      children with congenital insult. Fifty-six children (31 males and 25 females)
      with congenital hemiparesis and 14 control subjects were investigated. Of these
      children, 32 had a left hemisphere lesion, and 24 children had a right hemisphere
      lesion. There were 30 right-handed, 23 left-handed, and three ambidextrous
      children in the study group. The neuropsychologic assessment was performed using
      the NEPSY (a developmental neuropsychological assessment of child development)
      test battery. We found that 41% of the hemiparetic children and 72% of the
      children with a left hemisphere lesion were left-handed. In children
      contralateral to lesion handedness (no evidence of interhemispheric transfer of
      functions), we found diffuse cognitive deficits with impaired language abilities
      and poor visuomotor and narrative memory processing. In contrast, children with
      ipsilateral to brain lesion handedness (interhemispheric transfer of functions)
      demonstrated minimal or moderate side-specific cognitive dysfunction. Right
      handed children with a right hemisphere lesion had attention, spatial, and short
      term memory problems; left-handed children with a left hemisphere lesion had
      receptive language and visuomotor difficulties. Handedness combined with
      neuropsychologic assessment is a reliable indicator of the processes of cerebral
      reorganization after early brain insult.

PMID- 12504204
TI  - Macrocephaly in children with developmental disabilities.
AB  - In a community-based study of 4,309 children with neurodevelopmental disabilities
      who were referred to the Institute for Child Development, Tel Aviv, Israel, 62
      (1.4%) had macrocephaly (head circumference above the ninety-eighth percentile
      for age), of whom 42 (1%) had macrocephaly not associated with hydrocephalus.
      With the exception of neonatal respiratory distress the incidence of perinatal
      complications was not different from that in other children referred to the
      Institute for Child Development. In children with developmental disabilities,
      macrocephaly was a significant risk factor for febrile seizures (odds ratio =
      3.1, P < 0.001) and epilepsy (odds ratio = 7.7, P < 0.001), but not for mental
      retardation (odds ratio = 1.1, P = 0.78) or cerebral palsy (odds ratio = 1.3, P =
      0.67). Children with macrocephaly had a high rate of comorbid diagnosis. We
      conclude that in children with developmental disabilities the presence of
      macrocephaly even when not associated with hydrocephalus is associated with an
      increased risk of seizures.

PMID- 12504205
TI  - Clinical study of catastrophic infantile epilepsy with focal seizures.
AB  - This study investigated clinico-electrical and etiologic characteristics of
      catastrophic infantile epilepsy with focal seizures developed in early infancy.
      The patients included 15 children who fulfilled the following criteria: seizure
      onset before 12 months of age, presence of daily focal or secondarily generalized
      seizures resistant to antiepileptic drugs for at least 3 months, and exclusion of
      Ohtahara and West syndromes. Patients were classified into three subgroups. Three
      patients demonstrated progressively deteriorating neurologic symptoms associated
      with progressive cerebral atrophy and multifocal seizure onset. Three other
      children were characterized by hemiparesis and exclusively lateralized seizure
      onset because of focal cortical dysplasia in the contralateral hemisphere. The
      remaining nine children did not demonstrate any rapidly progressive neurologic
      deterioration or increasing cerebral atrophy and exhibited multifocal seizure
      onset. At the last examinations, all except one patient demonstrated moderate to
      severe psychomotor retardation. Catastrophic infantile epilepsy with focal
      seizures tended to demonstrate multifocal seizure onset and a deleterious
      clinical course with numerous focal seizures regardless of etiology. Because
      migratory focal seizures appear to be common in these infants, we have to search
      for the underlying etiopathogenesis of these patients, including not only
      metabolic errors but also localized or lateralized structural abnormality.

PMID- 12504206
TI  - Overuse of EEG in the evaluation of common neurologic conditions.
AB  - The objective of the present study was to analyze the diagnostic indications that
      most often prompt the referral of children and adolescents in the outpatient
      clinical pediatric practice for electroencephalographic evaluation and to check
      its utility in these clinical conditions. The electroencephalographic records of
      547 consecutive children and adolescents (5-16 years of age) referred to a single
      community laboratory for the evaluation of various neurologic disorders were
      prospectively read by a single blinded investigator. Common diagnostic
      indications included the following: clinical seizures (42%), attention-deficit
      hyperactivity disorder (23%), headaches (10.4%), syncope (9.9%), and tic disorder
      (4.9%). Overall, 76% of records were normal. Slowing of electroencephalographic
      activity was noted in 1% (attention-deficit-hyperactivity disorder) to 26%
      (probable epilepsy), and epileptiform activity in 53% of the probable and 29% of
      the clinically possible epileptics. Epileptiform activity was rarely found in the
      nonepileptic patients. The results of the present study demonstrate that standard
      interictal electroencephalogram is being overused during evaluation of various
      neurologic disorders in children and adolescents, suggesting that its use should
      be reserved for supporting the diagnosis in those cases in which epilepsy is a
      reasonable clinical possibility.

PMID- 12504207
TI  - Screening for autoantibodies in children with opsoclonus-myoclonus-ataxia.
AB  - Various paraneoplastic autoantibodies have been linked to discrete neurologic
      syndromes and tumors in adults, but little is known about their incidence in
      children. We report a cross-sectional study of known paraneoplastic antibodies in
      59 children with opsoclonus-myoclonus-ataxia, 86% of whom were moderately or
      severely symptomatic, and 68% of whom had relapsed at the time of testing. This
      total number of patients includes 18 children with low-stage neuroblastoma
      (tested after tumor resection), six of whom had never been treated with
      immunosuppressants. All were seronegative for anti-Hu, anti-Ri, and anti-Yo, the
      three paraneoplastic antibodies most associated with opsoclonus-myoclonus or
      ataxia in adults. These data contrast with reports of anti-Hu-positive sera in
      children with high-stage tumors and suggest that anti-Hu, anti-Ri, and anti-Yo do
      not explain relapses in pediatric opsoclonus-myoclonus-ataxia. They underscore
      the need to search for unique autoantibodies, as well as cellular mechanisms of
      pediatric paraneoplastic disease.

PMID- 12504208
TI  - Successful treatment of Ohtahara syndrome with chloral hydrate.
AB  - We present a patient with early infantile epileptic encephalopathy with
      suppression bursts (Ohtahara syndrome) with an excellent response to chloral
      hydrate to draw attention to a possible role of the "old" drug in the treatment
      of intractable epilepsy. Chloral hydrate (58 mg/kg/day) was used for a short-term
      administration in a 5-week-old female with typical features of cryptogenic
      Ohtahara syndrome after the failure of conventional antiepileptic drugs. Seizures
      disappeared in the course of 24 hours after the launch of chloral hydrate therapy
      and have not recurred. Results of electroencephalogram studies of the child
      demonstrate marked improvement. Psychomotor development is significantly delayed.
      Detailed diagnostic tests have not revealed any metabolic or structural
      abnormalities of the brain. We conclude that chloral hydrate could be useful in
      the treatment of severe epileptic encephalopathies. Possible indications of the
      drug for intractable epilepsy treatment are discussed.

PMID- 12504209
TI  - Epilepsia partialis continua associated with widespread gliomatosis cerebri.
AB  - We report an uncommon association of intractable epilepsia partialis continua
      that was the main presentation of widespread gliomatosis cerebri in two females.
      Both children had a preceding prolonged secondary generalized seizure 2-4 months
      before the evolution of epilepsia partialis continua, including recurrent
      clusters of left-sided myoclonic twitching and sensory impairment. During these
      events, the children remained fully alert. These seizures were corroborated by
      prolonged focal epileptic spike/wave discharges evident on the
      electroencephalograms. Cerebral magnetic resonance imaging in the first patient
      demonstrated a wide area of increasing signals over the right frontocentral
      regions, along with diffuse cortical-subcortical infiltration impinging on the
      left hemisphere. In the second patient a cortical lesion was suspected.
      Evaluation for Rasmussen's encephalitis, focal cortical dysplasia, or a
      gliomatous process was conducted; the patients underwent a stereotactic brain
      biopsy in which the histologic findings were compatible with gliomatosis cerebri
      with diffuse widespread infiltration of glioma cells with no constitution of a
      circumscribed tumor mass. The first patient was treated with cranial radiation,
      chemotherapy, steroids, and combined antiepileptic therapy. The focal seizures
      gradually but markedly decreased in frequency, and sensory impairment abated
      within 18 months after establishment of the diagnosis and ensuing therapy.
      Cognition remains intact. The second female died 2 years after presentation
      despite massive chemotherapy and antiepileptic medications. Although rare,
      gliomatosis cerebri should be taken into account in the differential diagnosis of
      epilepsia partialis continua in children to facilitate a rapid diagnosis and
      initiation of prompt treatment of this rare disorder that may respond to a
      concurrent effective combination of cranial radiation, chemotherapy, and
      antiepileptic medications.

PMID- 12504210
TI  - Atypical MELAS associated with mitochondrial tRNA(Lys) gene A8296G mutation.
AB  - We report on a unique patient with mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes (MELAS) presenting optic atrophy,
      cardiomyopathy, and bilateral striatal necrosis before stoke-like episodes became
      apparent. Skeletal muscle total mitochondrial DNA analysis identified a
      heteroplasmic A to G point mutation in the tRNA(Lys) gene at position 8296.
      Skeletal muscle pathology revealed typical MELAS findings, including ragged-red
      fibers cytochrome c oxidase positive strongly succinate dehydrogenase-reactive
      blood vessels. Recent reports describe the 8296 mutation identified in patients
      with diabetes mellitus or myoclonus epilepsy with ragged-red fibers, not MELAS.
      We conclude that the 8296 mutation is likely to be pathogenic and that it may be
      not only a mutation responsible for diabetes mellitus or myoclonus epilepsy with
      ragged-red fibers but also for MELAS.

PMID- 12504211
TI  - Macrocephaly and epidural involvement of T-cell acute lymphoblastic leukemia.
AB  - We describe a 2-year-old female who presented with macrocephaly and anemia.
      Magnetic resonance imaging revealed a diffusely enhancing epidural lesion over
      the sagittal frontoparietal region. Bone marrow examination confirmed the
      diagnosis of T-cell acute lymphoblastic leukemia. Induction chemotherapy led to
      hematologic remission and neuroimaging resolution of the mass. This report
      suggested macrocephaly could be a rare and early manifestation of leukemia in
      children.

PMID- 12504212
TI  - Medulloblastoma or cerebellar dysplastic gangliocytoma (Lhermitte-Duclos
      disease)?
AB  - Dysplastic cerebellar gangliocytoma is a rare benign tumor associated with
      specific neuroimaging findings of abnormal laminated or folial pattern in the
      posterior fossa. Some authors thus proposed that it could be diagnosed by
      neuroimaging studies alone. We encountered a patient with medulloblastoma in
      which the neuroimaging findings mimicked those of dysplastic gangliocytoma. In
      patients with a posterior fossa tumor suggestive of a dysplastic gangliocytoma on
      neuroimaging studies, a pathologic confirmation is necessary.

PMID- 12504213
TI  - Pseudostatus epilepticus in childhood.
AB  - Pseudostatus epilepticus in childhood has not been well reported in the
      literature. We describe the clinical presentation and management of a 9-year-old
      child with well-controlled epilepsy who presented in a prolonged period of
      pseudoseizures. Intensive care management over a number of weeks with multiple
      high-dose antiepileptic drugs, anesthesia, and ventilation at a tertiary care
      pediatric center was performed before the diagnosis of pseudostatus epilepticus
      was made. Initiation of family counseling and behavior therapy after diagnosis of
      the nonepileptic nature of the protracted paroxysmal events with video telemetry
      in our pediatric epilepsy unit was followed by remission. The patient reported
      herein illustrates the risks of iatrogenic morbidity that may result from a delay
      in the diagnosis of pseudoseizures and pseudostatus epilepticus in childhood.

PMID- 12504214
TI  - 108 children with migraine equivalents in 1,106 children with migraines in a
      period of 8 years.

PMID- 12504215
TI  - The bandwagon effect.

PMID- 12504216
TI  - The bio-intelligence age: surgery after the information age.

PMID- 12504217
TI  - Reasons for conversion from laparoscopic to open cholecystectomy: a 10-year
      review.
AB  - Laparoscopic cholecystectomy is now considered the "gold standard" operation for
      patients with gallstone disease. A number of patients require conversion to an
      open cholecystectomy for the safe completion of the procedure. This study
      investigates how the etiology and incidence of conversion from laparoscopic to
      open cholecystectomy has changed over time. All 5884 patients undergoing
      laparoscopic cholecystectomy between March 1991 and June 2001 were prospectively
      collected in a database. A total of 310 patients (5.2%) had had their
      cholecystectomies converted to an open procedure. The mortality rate for these
      patients was 0.7%. Causes for conversion were inability to correctly identify
      anatomy (50%), "other" indications (16%), bleeding (14%), suspected
      choledocholithiasis (11%), and suspected bile duct injury (8%). After an initial
      learning curve in thin patients with symptomatic cholelithiasis, inclusion of
      patients with acute cholecystitis, morbid obesity, or a prior celiotomy resulted
      in a peak conversion rate of 11% by 1994. From 1994 to the first half of 2001,
      the conversion rate has declined significantly for all patients (10% to 1%), as
      well as for patients with acute cholecystitis (26% to 1%). Although unclear
      anatomy secondary to inflammation remains the most common reason for conversion,
      the impact of acute cholecystitis on the operative outcome has decreased with
      time.

PMID- 12504218
TI  - Gallbladder function before and after fundoplication.
AB  - No study has reported an association between gastroesophageal reflux disease
      (GERD) or its therapies and gallbladder function. We compared pre- and
      postoperative gallbladder function in patients undergoing fundoplication to
      determine the following: (1) whether patients with chronic GERD have preexisting
      gallbladder motor dysfunction; (2) whether medical or surgical therapy alters
      gallbladder function; and (3) whether division of the hepatic branch of the
      anterior vagus nerve is detrimental to gallbladder motility. Nineteen patients
      with documented GERD consented to a preoperative cholecystokinin-stimulated
      technetium hepatobiliary (CCK-HIDA) scan to quantify the gallbladder ejection
      fraction (GBEF). All patients underwent laparoscopic Nissen fundoplication. One
      month after fundoplication, 12 patients completed a repeat CCK-HIDA scan for
      determination of GBEF, with comparison to the preoperative GBEF. Among patients
      with preoperative GERD, 11 (58%) of 19 met the scintigraphic criteria for
      gallbladder dysfunction (GBEF <35%), which is a ratio comparable to that in
      patients undergoing a CCK-HIDA scan for presumed biliary dyskinesia during the
      same time period (31 [60%] of 53; P = NS, chi-square test) and exceeds the rate
      of abnormal GBEF reported in healthy volunteers (3%). Six of seven patients with
      a low preoperative GBEF who underwent repeat evaluation postoperatively had
      normalization of the GBEF (P < 0.05, paired t-test). In the 12 patients who
      underwent postoperative CCK-HIDA scanning, there was no association between
      preservation or division of the hepatic branch of the anterior vagus nerve and
      postoperative gallbladder dysfunction (P = NS, chi-square test). Unexpectedly,
      58% of patients with GERD demonstrated gallbladder motor dysfunction prior to
      fundoplication, with improvement to normal occurring in most of those studied
      postoperatively. These data support controlled trials to determine the effect of
      chronic GERD and antisecretory therapy on gallbladder and global gastrointestinal
      smooth muscle function. Preservation of the hepatic branch of the anterior vagus
      nerve during fundoplication offered no clear benefit with regard to early
      postoperative gallbladder function.

PMID- 12504219
TI  - Long-term follow-up after laparoscopic refundoplication for failed antireflux
      surgery: quality of life, symptomatic outcome, and patient satisfaction.
AB  - Quality of life and patient satisfaction have been shown to be important factors
      in evaluating outcome of laparoscopic antireflux surgery (LARS). The aim of this
      study was to evaluate data pertaining to quality of life, patient satisfaction,
      and changes in symptoms in patients who underwent laparoscopic redo surgery after
      primary failed open or laparoscopic antireflux surgery 3 to 5 years
      postoperatively. Between March 1995 and June 1998, a total of 27 patients whose
      mean age was 57 years (range 35 to 78 years) underwent laparoscopic
      refundoplication for primary failed open or laparoscopic antireflux surgery.
      Quality of life was evaluated by means of the Gastrointestinal Quality of Life
      Index (GIQLI). Additionally, patient satisfaction and symptomatic outcome were
      evaluated using a standardized questionnaire. Three to 5 years after laparoscopic
      refundoplication, patients rated their quality of life (GIQLI) in an overall
      score of 113.4 points. Twenty-five patients (92.6%) rated their satisfaction with
      the redo procedure as very good and would undergo surgery again, if necessary.
      These patients were no longer taking any antireflux medication at follow-up. Two
      patients (7.4%) reported rare episodes of heartburn, which were managed
      successfully with proton pump inhibitors on demand, and four patients (14.8%)
      reported some episodes of regurgitation but with no decrease in quality of life.
      Seven patients (25.9%) suffer from mild-to-moderate dysphagia 5 years
      postoperatively, and 12 patients (44.4%) report having occasional chest pain but
      no other symptoms of gastroesophageal reflux disease. Nine of these patients
      suffer from concomitant cardiopulmonary disease. Laparoscopic refundoplication
      after primary failed antireflux surgery results in a high degree of patient
      satisfaction and significant improvement in quality of life with a good
      symptomatic outcome for a follow-up period of 3 to 5 years after surgery.

PMID- 12504220
TI  - Patients with upright reflux have less favorable postoperative outcomes after
      laparoscopic antireflux surgery than those with supine reflux.
AB  - The aim of this study was to compare symptomatic outcomes after laparoscopic
      antireflux surgery in patients with upright vs. supine reflux. A prospective
      database was used to assess postoperative clinical outcomes in relation to
      positional patterns of reflux in 117 patients. Supine reflux was present in 31%,
      upright in 24%, and the remaining 44% had bipositional reflux. Preoperatively
      there were no differences in the frequency of typical or atypical symptoms
      between groups. At a mean follow-up of 18 +/- 11 months postoperatively, there
      were marked differences in symptoms between groups. Patients with upright reflux
      noted significantly more heartburn, chest pain, odynophagia, and bloating
      postoperatively when compared to patients with supine and bipositional reflux (P
      < 0.05). According to visual analog scales, patients with upright reflux
      expressed less satisfaction with operative results, ascribing more symptoms to
      the esophagus and stomach, when compared to those with supine reflux (P < 0.05).
      Although all patients reported improvement, the extent of the relief from
      preoperative symptoms was less in patients with upright reflux (P < 0.05). When
      asked if, in retrospect, they favored operative therapy, the patients with
      upright reflux were less enthusiastic (P < 0.05). Although antireflux surgery
      eliminates reflux in nearly all patients, postoperative symptomatic outcome is
      related to the preoperative pattern of reflux. Although all patients showed
      symptomatic improvement, the extent of that improvement was significantly less in
      patients with upright reflux. These patients should be carefully counseled
      preoperatively regarding expected symptomatic outcomes.

PMID- 12504221
TI  - Slow progression of periampullary neoplasia in familial adenomatous polyposis.
AB  - Variable endoscopic surveillance protocols and treatment strategies have been
      proposed for periampullary neoplasia in familial adenomatous polyposis (FAP),
      primarily because of the lack of long-term, prospective natural history data. A
      total of 115 patients with FAP were followed prospectively for 10 years with
      periodic side-viewing upper gastrointestinal endoscopy by a single surgeon. The
      appearance of the duodenum was classified as stages 1 to 5. Statistical analysis
      included one-way analysis of variance for age comparisons between stage groupings
      and Kaplan-Meier analysis for the lifetime risks of having a particular stage of
      duodenal polyposis. Eighty-seven patients had multiple endoscopies over an
      average of 6.6 years. Thirty-three subjects had a change in stage, within an
      average time of 3.9 years at an average age of 41 years. The risk of having stage
      3 or 4 duodenal neoplasia increased exponentially after the age of 40. The degree
      of dysplasia did not correlate with stage at initial classification. Progression
      of neoplasia in the duodenum of patients with FAP is slow. The severity of
      duodenal polyposis increases with age and is not influenced by the initial stage.
      The average time for progression of adenoma to carcinoma is likely long.

PMID- 12504222
TI  - Selective cyclooxygenase-2 inhibitor rofecoxib (Vioxx) induces expression of cell
      cycle arrest genes and slows tumor growth in human pancreatic cancer.
AB  - Recent studies indicate that cyclooxygenase-2 (COX-2) is overexpressed in
      pancreatic adenocarcinoma and may play a critical role in this rapidly
      progressing form of cancer. A human pancreatic adenocarcinoma cell line, Mia PaCa
      2, was incubated for 18 hours with 5 micromol/L of rofecoxib (Vioxx), a selective
      COX-2 inhibitor. Total RNA was isolated and gene expression analyzed by DNA
      microarray chips. In a separate experiment, athymic mice were orthotopically
      injected with 7.5 x 10(5) Mia PaCa-2 cells through a minilaparotomy. After 1
      month, laparotomy was repeated to measure tumor size, and mice were randomized to
      receive reformulated rodent chow containing either 12.5 mg/kg/day of rofecoxib or
      no drug for 21 days. Tumor growth was assessed by comparing volume before and
      after treatment. In vitro, rofecoxib decreased gene expression of cyclin
      D1/PRAD1, a key component of cell cycle progression, while increasing expression
      of several cell cycle arrest genes, including p21/WAF1, p33/ING, GADD34, and
      GADD45 (P < 0.05). In vivo, tumor growth was significantly reduced in treated vs.
      control mice (P < 0.05). No systemic toxicity was observed in mice receiving
      rofecoxib. These data suggest that rofecoxib slows the growth of human pancreatic
      cancer through changes in gene expression that favor cell cycle arrest.

PMID- 12504223
TI  - Quality of life after bilateral thoracoscopic splanchnicectomy: long-term
      evaluation in patients with chronic pancreatitis.
AB  - We prospectively evaluated quality of life and visual analogue scale pain scores
      after bilateral thoracoscopic splanchnicectomy in 55 patients with small-duct
      chronic pancreatitis and abdominal pain. The perioperative morbidity rate was 11%
      and there were no perioperative deaths. Four late deaths occurred (7%), and three
      patients were lost to follow-up. Patients were divided into those who had prior
      operative or endoscopic interventions (N = 38) and those who did not (N = 17).
      Preoperatively there were no significant differences between the two groups with
      regard to age, sex, etiology, pain score, or narcotic use. Pain score, narcotic
      use, and symptoms scales improved significantly in both groups at 3 and 6 months
      postoperatively (P < 0.0001). The group with no prior surgical or endoscopic
      intervention did significantly better initially (P < 0.007), and the improvements
      in their quality-of-life and pain scores continued for the remainder of the
      study. In contrast, quality-of-life and pain scores in patients who had undergone
      prior surgical or endoscopic intervention returned to baseline by 12 months
      postoperatively and remained poor throughout the remainder of the study.
      Bilateral thoracoscopic splanchnicectomy appears to work best in patients who
      have had no prior operative or endoscopic interventions.

PMID- 12504224
TI  - National trends in utilization and in-hospital outcomes of bariatric surgery.
AB  - In view of recent enthusiasm for surgery to treat morbid obesity, we examined
      national changes in utilization and in-hospital outcomes of bariatric surgery
      over time. With the use of International Classification of Diseases (ICD-9)
      codes, we identified all bariatric procedures (n = 12,203) performed on adults
      from 1990 to 1997 in hospitals participating in the Nationwide Inpatient Sample.
      We then applied sampling weights and United States Census data to calculate the
      national population-based rates of bariatric surgery procedures for each year and
      examined secular trends in utilization. We further evaluated changes in patient
      characteristics and in-hospital mortality and complications. From 1990 to 1997,
      the national annual rate of bariatric surgery increased from 2.7 to 6.3 per
      100,000 adults (P < 0.001). The percentage of bariatric procedures performed by
      gastric bypass increased from 52% to 84% (P < 0.001). Patients were slightly
      older (38.1 years vs. 40.3 years; P < 0.001) with more comorbid conditions (20.9%
      vs. 31.6%; P < 0.001) in 1997 vs. 1990. In-hospital mortality was 0.37% overall
      and remained stable. Rates of pulmonary emboli, early reoperation, and pulmonary
      complications declined significantly over time. Between 1990 and 1997, the annual
      rate of bariatric surgery in the United States more than doubled, without
      substantial changes in perioperative morbidity or mortality. This trend was
      largely associated with an increase in the use of gastric bypass procedures.

PMID- 12504225
TI  - Surgical management of abdominal tuberculosis.
AB  - Recent reports suggest an increased incidence of abdominal tuberculosis in the
      United States, particularly in high-risk groups. The aim of this study was to
      review the spectrum of abdominal tuberculosis and its surgical management at a
      tertiary referral center in the United States. The medical records of patients
      treated for abdominal tuberculosis at our institution between January 1992 and
      June 2001 were retrospectively reviewed. Eighteen patients were diagnosed with
      abdominal tuberculosis by microbiologic and/or histologic examination. The 10 men
      and eight women had a mean duration of symptoms of 4 months (range 1 to 24
      months). Five were born in the United States, and 13 were foreign born (7 Asians
      and 6 Africans). The United States-born patients with abdominal tuberculosis, as
      compared to the foreign-born patients, were older (mean age 74 years vs. 35
      years), more likely to have chronic medical illnesses (80% vs. 7%), and had
      concomitant pulmonary tuberculosis (60% vs. 0%). Computed tomography was the most
      frequent imaging modality (88%); findings suggestive of abdominal tuberculosis
      were mesenteric/omental stranding (50%), ascites (37%), and retroperitoneal
      lymphadenopathy (31%). Seventeen of the 18 patients required operative
      intervention, and one patient underwent CT-guided drainage of a psoas abscess.
      Laparoscopy was useful for diagnosis in eight patients; laparotomy was performed
      for complications of abdominal tuberculosis in six patients and to obtain a
      tissue diagnosis in three patients. Abdominal tuberculosis continues to represent
      a diagnostic challenge to clinicians. Among native-born white Americans,
      abdominal tuberculosis is primarily a disseminated disease of elderly,
      debilitated patients with chronic illnesses. Among foreign-born individuals,
      abdominal tuberculosis occurs in young, immunocompetent patients from endemic
      areas. Characteristic CT findings should be evaluated for abdominal tuberculosis
      in the appropriate clinical setting. Laparoscopy is an effective modality for
      diagnosis of peritoneal tuberculosis.

PMID- 12504226
TI  - Adenomatous polyposis coli truncation alters cytoskeletal structure and
      microtubule stability in early intestinal tumorigenesis.
AB  - Partial loss of function of adenomatous polyposis coli (APC) protein by
      truncation of its carboxy (C)-terminus is an early factor in the development of
      many sporadic colorectal cancers. In the C57BL/6J Min/+ (Min/+) mouse, an animal
      with a germline mutation of Apc, we found that APC truncation was associated with
      reduced enterocyte migration and loss of association and membrane expression of
      adherens junction proteins. We hypothesized that these defects were related to
      changes in cytoskeletal function resulting from truncation of the APC C-terminus,
      which contains microtubule binding regions, as well as putative sites for
      indirect actin binding. We investigated this further by determining whether APC
      truncation produced in vivo changes in actin cytoskeletal structure and
      microtubule stability. The actin cytoskeleton of histologically normal
      enterocytes from Min/+ mice was compared to that of Apc+/+ (wild-type) mice by
      confocal indirect immunofluorescence microscopy. We found a significant loss of
      actin localization at the apical plasma membrane in Min/+ enterocytes. In
      addition, immunoblotting revealed increased levels of both unstable Tyr-tubulin
      and alpha-tubulin turnover in Min/+ enterocytes, indicating an alteration in
      microtubule dynamics. These studies suggest that loss of actin localization and
      changes in microtubule dynamics may be dominant negative effects of truncated
      APC. These changes are consistent with the defects in enterocyte migration and
      junctional complex formation observed in the Min/+ model of early APC-associated
      colorectal tumorigenesis.

PMID- 12504227
TI  - Activation of intestinal arginine transport by protein kinase C is mediated by
      mitogen-activated protein kinases.
AB  - L-Arginine uptake by the small intestine can play a pivotal role in regulating
      nitric oxide synthesis and immune functions in catabolic states. We previously
      showed that protein kinase C (PKC) activation stimulates intestinal brush-border
      membrane arginine transport. However, the signaling pathways implicated in this
      activation have not been studied. The purpose of this study was to investigate
      the intracellular signal transduction pathways involved in the protein kinase C
      stimulation of arginine transport across the apical membrane of intestinal
      epithelial Caco-2 cells. [3H]-L-arginine transport activity, Northern blot
      analysis of mRNA levels of the intestinal arginine transporter CAT1, and Western
      blot analysis of the mitogen-activated protein (MAP) kinases phospho-p44/42
      activity and phospho-MEK1/2 were measured in cultured Caco-2 cells treated with
      phorbol ester (phorbol 12-myristate 13-acetate, TPA; 0 to 0.5 micromol/L), and
      the MEK1 inhibitor PD 98059 (0 to 50 micromol/L). Phorbol ester stimulated
      intestinal arginine transport activity. Arginine transporter gene CAT1 mRNA,
      phospho-p44/42, and phospho-MEK1/2 levels were stimulated in phorbol ester
      treated cells, compared with the control group. Phorbol ester stimulation of
      arginine transport activity and transporter CAT1 mRNA levels was blocked by PD
      98059. These data suggest that phorbol ester stimulates arginine transport in
      Caco-2 cells via signaling pathways that lead to increased transcription and/or
      stabilization of CAT1 mRNA. Protein kinase C and MAP kinases MEK1/2 and p44/42
      are key intracellular regulators involved in this signal transduction cascade.

PMID- 12504228
TI  - Adequacy of nodal harvest in colorectal cancer: a consecutive cohort study.
AB  - The presence of nodal metastasis is a critical component of staging in colorectal
      cancer. Accurate assessment of nodal status requires sufficient node sampling,
      although the number of such nodes is controversial, with recommendations ranging
      from 6 to 17 nodes. The purpose of this study was to describe the nodal harvest
      in colorectal cancer and to identify factors associated with adequate lymph node
      harvest. Pathology reports from consecutive patients with newly diagnosed
      colorectal cancer undergoing resection between January 1997 and December 2000 at
      a tertiary care academic institution were reviewed. Identification of 12 or more
      lymph nodes was considered to be an adequate nodal harvest based on the current
      American Joint Committee on Cancer recommendations. Among the 579 consecutive
      specimens, the number of nodes identified was not stated for 10 (1.7%). Of the
      remaining 569 specimens, 4700 nodes were identified with a mean of 8.3 nodes per
      patient (median 7, range 0 to 60). Nodal metastases were identified in 219
      patients (38.5%). Patients with one or more positive nodes had greater nodal
      harvest than those with negative nodes (9.5 vs. 8.2, respectively; P = 0.03).
      Only 22.4% of patients were found to have an adequate nodal harvest (> or =12
      nodes). Right-sided resections, high surgeon volume, and gross examination of
      specimens by a staff pathologist were associated with higher nodal harvests,
      compared to left-sided resections, low surgeon volume, and gross examination of
      specimens by a pathology resident/technologist, respectively. There was no
      association with pathologist volume. In this study, nodal harvest in patients
      undergoing resection for colorectal cancer was highly variable. This problem
      appears to be multifactorial, and is related to patient, pathologic, and surgical
      factors.

PMID- 12504229
TI  - Pathogenesis of pigment gallstones in Western societies: the central role of
      bacteria.
AB  - Bacteria are traditionally accorded a greater role in pigment gallstone formation
      in Eastern populations. Stone color is thought to predict the presence of
      bacteria; that is, black stones (Western predominant) are supposedly sterile and
      brown stones (Eastern predominant) contain bacteria. We previously reported that,
      regardless of appearance, most pigment gallstones contain bacteria. This study
      examined, in a large Western population (370 patients), the incidence,
      appearance, and chemical composition of pigment stones, and the characteristics
      of gallstone bacteria. One hundred eighty-six pigment stones were obtained
      aseptically. Bacteria were detected by means of scanning electron microscopy and
      gallstone culture. Chemical composition was determined by infrared spectroscopy.
      Bacteria were tested for slime and beta-glucuronidase production. Seventy-three
      percent of pigment stones contained bacteria. Choledocholithiasis was associated
      with gallstone bacteria. Ca-bilirubinate was present in all pigment stones. Ca
      palmitate was characteristic of infected stones, and more than 75% Ca-carbonate
      was characteristic of sterile stones. Neither chemical composition nor stone
      appearance predicted the presence of bacteria. Ninety-five percent and 67% of
      infected pigment stones contained bacteria that produced slime and beta
      glucuronidase, respectively. Most pigment stones contained bacteria that produced
      beta-glucuronidase, slime, and phospholipase, factors that facilitate stone
      formation. Thus bacteria have a major role in Western pigment gallstone
      formation. Furthermore, gallstone color did not predict composition or bacterial
      presence.

PMID- 12504230
TI  - Portal vein embolization vs. portal vein ligation for induction of hypertrophy of
      the future liver remnant.
AB  - The objective of this study was to assess the efficacy of right portal vein
      embolization (PVE) vs. right portal vein ligation (PVL) for induction of
      hypertrophy of the left lateral liver lobe before extended right hepatectomy.
      Thirty-four patients with primary or secondary liver tumors and estimated remnant
      functional liver parenchyma of less than 0.5% of body weight underwent either
      right PVE (transcutaneous, n = 10; transileocolic, n = 7) or right PVL (n = 17).
      Liver volume was assessed by CT scan before occlusion of the right portal vein
      and prior to resection. There were no deaths. The morbidity rate in each group
      was 5.8% (PVE, 1 abscess; PVL, 1 bile leak). The increase in liver volume was
      significantly higher after PVE compared with PVL (188 +/- 81 ml vs. 123 +/- 58
      ml) (P = 0.012). Postoperative hospital stay was significantly shorter after PVE
      in comparison to PVL (4 +/- 2.9 days vs. 8.1 +/- 5.1 days; P < 0.01). Curative
      liver resection was performed in 10 of 17 patients after PVE and 11 of 17
      patients after PVL. PVE and PVL were found to be feasible and safe methods of
      increasing the remnant functional liver volume and achieving resectability for
      extended liver tumors. PVE results in a significantly more efficient increase in
      liver volume and a shorter hospital stay.

PMID- 12504232
TI  - [Hypocholesterolemia: a risk factor for mortality?].

PMID- 12504233
TI  - [Cerebral-vein thrombosis: retrospective study of twenty seven cases].
AB  - PURPOSE: Among the locations of venous thrombosis, even if rare, cerebral-vein
      thrombosis is a severe event with a high mortality rate. No aetiology is found in
      20 to 30% of the cases. In recent years, inherited coagulation disorders have
      been described, as risk factors for venous thrombosis. We report the results of a
      retrospective study of 27 patients who suffered cerebral-vein thrombosis, in
      which coagulation abnormalities have been searched for. METHOD: The patients were
      referred to the haemostasis laboratory of the Henri Mondor hospital between
      august 1982 and June 1988, after a cerebral-vein thrombosis. The predisposing
      factors, personal and family history of thromboembolism, clinical presentation,
      thrombosis location, evolution under treatment and long-term outcome, have been
      noted. Deficiencies in antithrombine, protein C, protein S, the Factor V Leiden
      and the G20210A prothrombin-gene mutation, the presence of lupus anticoagulant,
      of anticardiolipin antibodies as well as a hyperhomocysteinaemia have been
      searched, either at the initial presentation, or a posteriori. RESULTS: Fourty
      one percent of patients had a coagulation abnormality. The prevalence of the
      different abnormalities was: inherited deficiency in AT 7.4%, in PC 8%, in PS
      12.5%, factor V Leiden mutation 12%, G20210A prothrombin-gene mutation 12%. Two
      patients had combined defects: AT and PC deficiency in one, F V Leiden and F II
      G20210A mutations in one. e of the patient had lupus anticoagulant. Three
      patients had a significant rate of anticardiolipin antibodies. Five patients out
      of eight displayed a moderate hyperhomocysteinaemia. Nothing (past history, age,
      predisposing factors) distinguished those patients bearing a coagulation disorder
      from the others. The venous thromboembolic relapse rate of 15 % (4/27 patients).
      Three of them had an inherited thrombophilic abnormality. CONCLUSION: We
      recommend an investigation of the haemostasis after every cerebral venous
      thrombosis.

PMID- 12504234
TI  - [Systemic lupus erythematosus in 24 tunisian males: clinico-biological analysis
      and clinical course].
AB  - PURPOSE: The systemic lupus erythematosus (SLE) is rare at the male. The clinic
      and biological characteristics and the evolution are variable between different
      studies. From 24 Tunisian observations we try to contribute to the precision of
      these characteristics on this ground. METHOD: It's a tunisian, multicentric,
      retrospective study of 24 males lupus, follow-up from 1990 to 1999 within a total
      lupus cohort of 295 patients. RESULTS: The sex-ratio female/male is 11/29, mean
      age at diagnosis is 31.75 years (range 10 to 63). The most frequent clinical
      manifestations are: arthritis (95%), malar rash (71%), photosensitivity (41%),
      glomerular nephropathy (66%) (classes III and IV = 7 cases/9), the serositis
      (37.5%) and Raynaud phenomenon (25%). Comparing these characteristics of two
      patient groups (24 males and 271 females), significant difference was observed :
      vascular thrombosis in male (16% vs 4% p : 0,027) and alopecia in female (12.5%
      vs 4% p : 0.03). For the other manifestations as nephropathy and serositis which
      are frequent in male the difference was not significant. The overall survival
      rate at 5 years 93% is and it was nearly the same in woman SLE patients.
      CONCLUSION: SLE in male is rare. In SLE male patients vascular thrombosis and
      nephropathy are more frequent without survival's influence.

PMID- 12504235
TI  - [Hypocholesterolemia in hospitalized elderly: relations with inflammatory and
      nutritional status].
AB  - PURPOSE: Hypocholesterolemia is a common finding in hospitalized elderly people
      and is associated with increased mortality. Changes in plasma lipid levels are
      well known in the acute phase response. It has also been suggested that
      malnutrition is a cause of hypocholesterolemia. However, malnutrition is the
      reflect of general condition, and the respective roles of malnutrition and
      inflammation have not yet been clearly established. This research project was
      undertaken to examine the impact of nutritional and inflammatory status on the
      hypocholesterolemia. METHODS: In a prospective study, 597 elderly patients (83 +/
      7 years) consecutively admitted in a geriatric acute care unit were included.
      Clinical and anthropometric data: Body Mass Index (BMI), Tricipital Skinfold
      Thickness (TSF), Sub-Scapular Skinfold Thickness (SSF), Mid Arm Circumference
      (MAC) have been collected. The blood samples were obtained within the 72 hours
      following the admission. Nutritional proteins (albumin, prealbumin, transferrin,
      retinol binding protein); inflammatory proteins (CRP, alpha-1 acid glycoprotein),
      and blood lipids (cholesterol, LDL, HDL cholesterol, triglycerides, apoproteins
      A1 and B) were dosed. RESULTS: The anthropometric and biologic parameters have
      been compared on the two sexes, significant differences were observed only for
      blood lipids. The analyses are thus realized and presented by sex separately.
      Four groups of patients are generated according to the quartile of total
      cholesterol. Means and standard deviation for all factors are calculated within
      each group. Both, the trend of means and analyses of correlation show
      associations with cholesterol in the two sexes. The analysis of variance showed
      that the cholesterolemia is associated with 1/ decrease in the values of the
      anthropometrics, and nutritional proteins and 2/ upward trends of the
      inflammatory parameters. Significant correlations were observed for all transport
      proteins and CRP with total cholesterol in men and women. The multiple linear
      regression of the total cholesterol retained albumin, APO A1, APO B and RBP as
      predictor factors of cholesterolemia for women and APO A1, APO B and tryglicerid
      for men. When patients with infectious diseases were compared to the others,
      significant differences have been observed for total cholesterol and all blood
      lipids, as well as for nutritional and inflammatory proteins. CONCLUSION: The
      results confirm an association between nutritional status and
      hypocholesterolemia, and suggest also the responsability of inflammation as a
      cause of hypocholesterolemia.

PMID- 12504236
TI  - [The treatment of prostatitis].
AB  - PURPOSE: Prostatitis are frequently recognized in general practice and often are
      a diagnosis and therapeutic challenge. We review here the updated knowledge on
      diagnosis and therapy of prostatitis. CURRENT KNOWLEDGE AND KEY POINTS:
      Prostatitis are divided into acute bacterial prostatitis (I), chronic bacterial
      prostatitis (II), chronic prostatitis/ chronic pelvic pain syndrome (III) and
      asymptomatic inflammatory prostatitis. Chronic prostatitis/ chronic pelvic pain
      syndrome are divided into : inflammatory (IIIA) and noninflammatory (IIIB).
      Treatment of prostatitis should follow evidence based guidelines recently
      published. Acute prostatitis should be treated by ciprofloxacine 500 mg tid or
      ofloxacine 200 mg bid or cotrimoxazole 960 mg bid for 4 weeks (CIII). When
      bacteremia occurs third generation cephalosporin with gentamicin should be used
      (CIII). In chronic bacterial prostatitis ciprofloxacine 500 mg tid or ofloxacine
      200 mg bid or norfloxacine 400 mg bid or cotrimoxazole 960 mg bid for 4 weeks may
      be used (BIII). FUTURE PROSPECTS AND PROJECTS: Molecular techniques should
      improve the etiological diagnosis of prostatitis and their treatment.

PMID- 12504237
TI  - [Treatment of rheumatoid arthritis by interleukin-1 receptor antagonist].
AB  - PURPOSE: Interleukin -1 receptor antagonist ( IL-1Ra ) is a new option among
      biotherapies against rheumatoid arthritis ( RA ). THE AIM: of this review is to
      recall the rationale of use of IL-1Ra and to analyse the results available in the
      current literature. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiological data of
      RA give a specific position for IL-1 as a potential target for immunotherapy in
      this disease, confirmed in animal models. Phase II and III studies with IL-1Ra
      (Anakinra) demonstrated clinical efficacy versus placebo (42% responders in ACR
      20 in Anakinra + methotrexate, and 23% in the placebo + methotrexate group at 24
      weeks) and a structural effect (slowing of radiological progression at six
      months). Anakinra has obtained an European license and is indicated in RA not
      controlled by methotrexate, in daily subcutaneous administration (100 mg/day), in
      combination with methotrexate. Tolerance is fair; the most frequent side effect
      is represented by injection site reactions. FUTURE PROSPECTS AND PROJECTS: This
      ambulatory biotherapy offers new perspectives in combination with other slow
      acting drugs as well as biologic agents such as anti-TNF, currently under
      evaluation.

PMID- 12504238
TI  - [Ovarian vein thrombophlebitis and post-partum fever].
AB  - INTRODUCTION: Ovarian vein thrombophlebitis (OVT) is a rare but potentially
      threatening complication of the postpartum period. Diagnosing it may be of some
      difficulty especially in case of symptoms mimicking appendicitis or
      pyelonephritis. EXEGESIS: We report 2 patients with postpartum right OVT. The
      clinical presentation included high grade fever, and pain, lumbar in one case, of
      the right flank in the other. Pulmonary embolism complicated both cases.
      CONCLUSION: Diagnostic and therapeutic management of OVT was transformed by
      progresses in medical imaging during the 1980's. However, optimal duration of
      anticoagulant treatment and secondary prevention indications have to be
      determined.

PMID- 12504239
TI  - [Systemic lupus erythematosus and herpes virus infection: three new
      observations].
AB  - INTRODUCTION: Systemic lupus erythematosus is still of unknown origin. Viruses
      have long been postulated to play a role in its pathogenesis particularly
      cytomegalovirus and Epstein-Barr virus. EXEGESE: We describe three patients who
      presented acute onset of systemic lupus erythematosus concurrently with recent
      viral infection (two with cytomegalovirus and one with Epstein-Barr virus).
      CONCLUSION: The peculiar clinical events emphasize the difficulty of diagnosis at
      the onset of the disease and suggest possible role of these viruses in the
      pathogenesis of SLE.

PMID- 12504240
TI  - [Determination of regimen fluindione needed for anticoagulation in the elderly].
AB  - INTRODUCTION: There is no validated method to predict the daily maintenance
      dosage of oral anticoagulation treatment by fluindione in the elderly patients.
      The aim of our prospective study was to look for a relation between INR at day 2
      after a fixed dosage of fluindione and the daily maintenance dosage of fluindione
      necessary to obtain an INR value between 2 and 3. PATIENTS AND METHODS: Ten
      milligrams of fluindione were administered on first and second day of treatment.
      INR was determined the third day. RESULTS: From this value, we were able to
      determine the daily dosage of fluindione (+/- 5mg) that maintained a steady state
      INR value between 2 and 3. CONCLUSION: In these very elderly patients, there was
      a relation between INR at the third day after a fixed dosage of fluindione and
      the daily maintenance dosage of fluindione necessary to obtain an INR value
      between 2 and 3.

PMID- 12504241
TI  - [Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (Melas) associated with a Fahr disease and cerebellar calcifications].
AB  - INTRODUCTION: Melas syndrome is a mitochondrial disease which corresponds to the
      association of mitochondrial encephalopathy, lactic acidosis and stroke-like
      espisodes. CASE REPORT: The authors report the case of a 39 year-old woman
      presenting with hearing loss, seizures, visual field deficit, three stroke-like
      episodes and calcifications of the basal ganglia and cerebellar dentate nuclei.
      Melas syndrome was suspected and confirmed by muscle biopsy, showing ragged red
      fibers and the presence of an A3243G mutation of mitochondrial DNA. CONCLUSION:
      This clinical, pathological and radiological observation shows that intracerebral
      calcifications may involve the dentate nuclei of the cerebellum in the Melas
      syndrome.

PMID- 12504242
TI  - [Thoracic actinomycosis sensitive to amoxicillin].

PMID- 12504243
TI  - [Systemic sclerosis sine scleroderma revealed by pulmonary interstitial
      fibrosis].

PMID- 12504244
TI  - [Recurrent cholestatic jaundice in adult-onset Still's disease].

PMID- 12504245
TI  - [Bartonella Quintana infective endocarditis in an immunocompetent Senegalese
      man].

PMID- 12504246
TI  - [Antiphospholipid antibodies and Gaucher's disease. A case report].

PMID- 12504250
TI  - Effects of metabolites on the structural dynamics of rabbit muscle pyruvate
      kinase.
AB  - The activity of rabbit muscle pyruvate kinase (PK) is regulated by metabolites.
      Besides requiring the presence of its substrates, PEP and ADP, the enzyme
      requires Mg(2+) and K(+) for activity. PK is allosterically inhibited by Phe for
      activity. The presence of PEP or Phe has opposing effects on the hydrodynamic
      properties of the enzyme without an apparent change in secondary structure. In
      this study, the structural perturbation induced by ligand binding was
      investigated by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, the
      structural dynamics of PK was probed by H/D exchange monitored by FT-IR.
      Substrates and activating metal ions induce PK to assume a more dynamic structure
      while Phe exerts an opposite effect. In all cases there is no significant
      interconversion of secondary structures. PEP is the most efficient ligand in
      inducing a change in the microenvironments of both helices and sheets so much so
      that they can be detected spectroscopically as separate bands. These results
      provide the first evidence for a differential effect of ligand binding on the
      dynamics of structural elements in PK. Furthermore, the data support the model
      that allosteric regulation of PK is the consequence of perturbation of the
      distribution of an ensemble of states in which the observed change in
      hydrodynamic properties represent the two extreme end states.

PMID- 12504251
TI  - NMR study of the conformational transition of cytochrome c upon the displacement
      of Met80 by exogenous ligand: structural and magnetic characterization of
      azidoferricytochrome c.
AB  - As the exogenous ligand-cytochrome c complexes were purported to represent models
      for the unfolding intermediate of cytochrome c, NMR spectroscopy has been
      utilized to study the azide adduct of horse heart cytochrome c. The structure of
      azidoferricytochrome c was modeled by restrained energy minimization using
      paramagenetic pseudocontact shifts as constraints. The bound azide moiety was
      found to be tilted approximately 15 degrees from the heme normal. The
      displacement of Met80 by the exogenous azide molecule causes large structural
      rearrangement in the distal cavity. Furthermore, the conformation transition
      associated with the swing out of the loop containing Met80 and the shift of the
      50s-helix increases the solvent accessibility of the heme group. To elucidate the
      heme electronic structure of the complex, the paramagnetic 13C shifts were
      analyzed in terms of a model based on the pi molecular orbitals of the heme under
      perturbed D(4) symmetry. It turned out that the His-Fe bonding provides the
      protein constraint that orients the in-plane anisotropy in the complex. The
      electronic properties are in accordance with the calculated magnetic
      susceptibility anisotropy and the structural information.

PMID- 12504252
TI  - Thermal stability of the human blood serum acid alpha(1)-glycoprotein in acidic
      media.
AB  - Thermal stability of human alpha(1)-acid glycoprotein and its desialyzed form
      were studied in the pH range of 1.5-5.2, i.e. about its pI. Circular dichroism,
      fluorescence and UV-absorption were used to determine the conformational changes
      and their reversibility in the temperature range 25-80 degrees C. These changes
      were tested in a three step process-heating, cooling and a second heating.
      Principal component analysis was applied for analyzing the spectral sets obtained
      in these experiments. Fully reversible behavior of Trp residues, as characterized
      by fluorescence spectroscopy, was observed during the heating process at all pH
      values. Nevertheless, three different types of the protein motion (reversible,
      irreversible and rearrangement of the protein core) were determined by UV
      absorption spectroscopy. Thus, an environment of Tyr and Phe is modified or
      reversibly rearranged during the heating process in acid media. These types of
      alpha(1)-acid glycoprotein behavior were not significantly affected by
      desialyzation.

PMID- 12504253
TI  - Statistical analysis of pair-wise compatibility of spatially nearest neighbor and
      adjacent residues in alpha-helix and beta-strands: application to a minimal model
      for secondary structure prediction.
AB  - Secondary structural elements like alpha-helix and beta-strands possess
      distinctly different structural features and thus the relative positioning of the
      nearest neighbor residues, and also the sequence-wise adjacent residues is
      important in determining the structural preference. In the present work we have
      statistically examined the pair-wise compatibility pattern of physically nearest
      neighbors and separately the adjacent residue pairs along the sequence in between
      the nearest neighbor partners in alpha-helices and beta-strands. It has been
      demonstrated that the patterns and hence, the physical basis of the compatibility
      of adjacent residue pairs and the spatially nearest neighbors are significantly
      different in most cases. The influence of tertiary contacts on the pair-wise
      compatibility is shown to be significant for beta-strands while it is small for
      alpha-helices. Based on the compatibility of physically nearest neighbors and the
      sequence-wise adjacent residue pairs, a minimal model has been constructed to
      predict the alpha-helices, beta-strands and coils of a protein from its sequence.
      Application of this method to 100 sequences shows that it has a predictive
      capability comparable to that of other more sophisticated statistical methods.

PMID- 12504254
TI  - Conformational study of linear and cyclic peptides corresponding to the 276-284
      epitope region of HSV gD-1.
AB  - The results of conformational analysis of linear and cyclic peptides from the
      276SALLEDPVG(284) sequence of glycoprotein D of Herpes simplex virus are
      presented. The epitope peptides were synthesized by SPPS and on resin cyclization
      was applied for preparation of cyclic compounds. Circular dichroism spectroscopy,
      Fourier-transform infrared spectroscopy and nuclear magnetic resonance (NMR) were
      used to determine of the solution structure of both linear and cyclic peptides.
      The results indicated that the cyclopeptides containing the core of the epitope
      (DPVG) as a part of the cycle have more stable beta-turn structure than the
      linear peptides or the cyclic analogues, where the core motif is not a part of
      the cycle. NMR study of H-SALLc(EDPVGK)-NH(2) confirm presence of a type I beta
      turn structure which includes the DPVG epitope core.

PMID- 12504255
TI  - Ferricytochrome c encapsulated in silica hydrogels: correlation between active
      site dynamics and solvent structure.
AB  - Ferricytochrome c encapsulated in silica hydrogels has been prepared by the sol
      gel technique following, with some modifications, the procedure originally
      developed by Ellerby et al. (Science 255 1113 (1992)). A suitable preparation of
      hydrogels enables having both 'wet' and 'dry' samples. Wet samples have a high
      water content: as the temperature is lowered below approximately 260 K, water
      freezes and the samples crack. On the contrary, dry samples have a low water
      content (hydration h approximately equal 0.35): in these conditions water does
      not freeze even at cryogenic temperatures and the samples remain transparent and
      non-cracking. The dynamics of ferricytochrome c and its dependence on the
      surrounding medium have been studied by optical absorption spectroscopy in the
      temperature range 10-300 K. At each temperature, spectra were collected both in
      the Soret region and in the near infrared at approximately 1.45 microm (the water
      overtone band); this enables probing the local dynamics of the protein active
      site as well as the 'structure' of water molecules present in the sample. The
      data show that sol-gel encapsulation 'per se' does not alter the protein active
      site dynamics, but rather introduces an increased local heterogeneity. We find a
      correlation between active site dynamics and water structure: in the wet
      hydrogel, freezing of water quenches the ensemble of soft modes linearly coupled
      to the Soret transition; while, in the dry hydrogel, water does not freeze and an
      active site dynamic behavior--similar to the non-freezing water/glycerol solution
      -is observed.

PMID- 12504256
TI  - Net proton charge of beta- and kappa-casein in concentrated aqueous electrolyte
      solutions.
AB  - Titration experiments have been carried out in order to measure the net proton
      charge of beta- and kappa-casein in NaCl solutions at 0.1 M and 1 M salt
      concentrations, at 4 degrees C, in the pH range between 5.5 and 10.5.
      Experimental data are compared with model values calculated through pK(a)'s of
      titrable groups neglecting the electrostatic perturbation term (deltapK(a)) in
      order to evaluate the magnitude of the error caused by this approximation and to
      delimit its effectiveness. At both ionic strengths, the agreement is good for
      kappa-casein in the pH range [5.5, 9.5], while errors of up to 2 charges are
      observed for beta-casein in the same range. These deviations are likely to be
      caused by strong electrostatic effects induced by the high density of negative
      charges of beta-casein 1-21 peptide. In order to account for these electrostatic
      effects, the net proton charge on this peptide is evaluated through a model based
      on the counterion condensation theory developed for the titration of
      polyelectrolytes with different types of ionizable groups.

PMID- 12504257
TI  - Effect of solvent viscosity, polarity and pH on the charge transfer between
      tryptophan radical and tyrosine in bovine serum albumin: a pulse radiolysis
      study.
AB  - The effect of viscosity, solvent polarity and pH of the medium on the reaction of
      a protein, bovine serum albumin (BSA), with organohalo-peroxyl radical in aqueous
      solution has been studied using pulse radiolysis technique. Unlike in dilute
      aqueous solution, electron transfer from tyrosine to tryptophan radical in BSA
      has been clearly observed at a viscosity of 7.7 centiPoise (cP). The oxidation of
      BSA, tryptophan and tyrosine in different media has also been compared with those
      taking place in dilute aqueous solution. The effect of solvent characteristics on
      the observed charge transfer has been discussed.

PMID- 12504258
TI  - Priorities and satisfaction on the help needed and provided in a first episode of
      psychosis. A survey in five European Family Associations.
AB  - In the case of a first episode of psychosis among members of different
      associations of families of mentally ill people, little is known about their
      priorities and how satisfied they are with the help provided to them. A survey
      was conducted in five European family associations. Respondents emphasized the
      need for early (ambulant) intervention through outreach with very practical goals
      directed at creating stability and social functioning. About one-third of the
      respondents are unsatisfied or very unsatisfied. The highest percentage of
      unsatisfied respondents was in the following five areas of care: advice on how to
      handle specific problems; help with preserving or regaining social functioning;
      help with regaining structure and routine; information; prompt assistance
      preferably in patients own environment. The agreement of these findings with
      findings from earlier studies underlines the importance of suggesting specific
      changes in the delivery of care.

PMID- 12504259
TI  - Service utilisation and costs of first-contact patients in a community
      psychiatric service in Italy.
AB  - This study describes service utilisation under routine clinical activity and the
      costs of providing mental health care for 24 months for the whole population of
      330 subjects who had first contact with the Magenta Community Mental Health
      Centre during one year. The mean age of patients was 42.5 years, and 61% were
      females. According to ICD 10 criteria, 7% were diagnosed as having schizophrenia,
      22% mood disorders, 37% neurotic disorders, 15% personality disorders and 19%
      other diagnoses. The clinical routine activity was monitored for 24 months from
      the first contact for each patient. The mean cost for a schizophrenic patient is
      more than double that of other patients. In-patient activity and community
      services accounted, respectively, for 49.7% and 50.3% of the total costs. Total
      health care costs per patient differ widely according to whether patients had
      been hospitalised during the observation period. Patients with a previous
      psychiatric contact and a longer duration of illness were more costly than the
      other patients. Multiple regression analysis was used to assess the association
      between all the individual variables and costs. For the whole population, the
      model explains 50% of the cost variation. Higher treatment costs were positively
      associated with the presence of previous psychiatric contacts and referral to the
      CPS by other sources than a general practitioner, and negatively associated with
      age.

PMID- 12504260
TI  - Psychiatric disorders and social characteristics among second-generation Moroccan
      migrants in Belgium: an age-and gender-controlled study conducted in a
      psychiatric emergency department.
AB  - PURPOSE: Clinically, one of the most consistent clinical findings among migrant
      patients is an increase in the rate of psychosis. The aim of the present study
      was to confirm this finding in Belgium by comparing second-generation Moroccan
      migrant patients with Belgian patients, matched for the variables of age and
      gender. SUBJECTS AND METHOD: We conducted a cross-sectional survey on 272
      patients admitted in a psychiatric emergency unit during the year 1998. We used
      univariate and multivariate analyses to compare the two subgroups. RESULTS:
      Multivariate analyses showed that migrant patients lived more often with their
      parental family and that they presented a higher rate of admission for psychotic
      disorders and a lower rate of employment. DISCUSSION: Our findings add to the
      growing body of results showing increased incidence of psychosis among immigrants
      to European countries, but several factors have to be taken into account,
      particularly with regard to selection biases and differences in help-seeking
      behaviour and in family perception of the mental illness. CONCLUSION: Our results
      are compatible with the hypothesis that unemployment is a contributing factor in
      the risk for psychosis among migrant groups. Further studies would be needed to
      better explain some of our results, particularly the role played by the families
      of migrant patients.

PMID- 12504261
TI  - Belief systems as coping factors for traumatized refugees: a pilot study.
AB  - The severity of traumatization seems to correlate with a more severe course of
      post-traumatic stress disorder (PTSD) (and other post-traumatic disorders), while
      firm belief systems have been found to be a protective factor against post
      traumatic disorders. This study sought to determine the role of belief systems in
      the outcome of psychotherapy for traumatized refugees. The charts of 141
      consecutively treated refugees were evaluated retrospectively. A firm belief
      system was found to be an important predictor for a better therapy outcome. The
      importance of a firm belief system as a coping factor, which should be used as an
      instrument in therapy, is discussed.

PMID- 12504262
TI  - Risperidone in chronic schizophrenia: a detailed audit, open switch study and two
      year follow-up of patients on depot medication.
AB  - Little information exists on the medium- to long-term outcome of switching
      patients with schizophrenia from traditional depot to atypical oral antipsychotic
      agents. By detailed clinical audit, we identified a representative group of 102
      patients of an Irish psychiatric service with DSM-IV chronic schizophrenia and on
      depot neuroleptics for a mean of 15 years. Of 69 eligible to participate, 33
      entered a 6-month switch study of risperidone, with limited follow-up of
      consenters and non-consenters at 1 and 2 years. At 6 months, 23 of 33 were still
      on risperidone and had small significant improvements in clinical and
      extrapyramidal side effects, QOL and adjunct medication measures over baseline.
      At 12 months, 19 of 33 were still on risperidone, reducing to 13 of 33 at 2
      years. At 2 years, of 32 surviving consenters to switch, 19 had suffered
      clinically detrimental events and were no longer on risperidone, compared to none
      of the 33 surviving non-consenters, who were all still on depot. These findings
      suggest that switching from depot to risperidone may encounter high rates of
      refusal and attrition subsequent to switch. While a majority of switched patients
      may improve to least 6 months, audit plus switch may have clinically unfavourable
      effects on others over a 2-year follow-up period [corrected].

PMID- 12504263
TI  - How safe are psychiatric medications after a voluntary overdose?
AB  - PURPOSE: This study assessed psychiatric medications and their potential
      lethality in a representative sample of suicide attempts. MATERIALS AND METHODS:
      During 1996-98, 563 suicide attempts were studied in a general hospital in Madrid
      (Spain). Medication overdose was used in 456 suicide attempts (81%). The ratio
      between dose taken and maximum prescription dose recommended was used to evaluate
      the medication toxicity. RESULTS: Benzodiazepines were the drugs most often used
      in self-poisoning (65% of overdoses), followed by new antidepressants (11%),
      tricyclic antidepressants (TCAs) (10%), and antipsychotics (8%). An overdose with
      any of the three latter psychiatric medications was significantly more frequent
      in patients prescribed those medications. The overdoses for TCA were potentially
      lethal in 47% of the cases. However, all patients who overdosed on psychiatric
      medications recovered well and were discharged without any sequelae. DISCUSSION:
      This study suggests that psychiatric medications, particularly benzodiazepines,
      new antidepressants and antipsychotics, are relatively safe when they are used
      for self-poisoning. If patients with mental illnesses are under treated, there is
      a clear and documented higher risk for suicide. CONCLUSION: It is better to
      prescribe psychiatric medications, particularly the new ones, rather than
      withhold them due to an exaggerated fear of a lethal overdose

PMID- 12504264
TI  - Use of antipsychotic agents in Spain through 1985-2000.
AB  - OBJECTIVE: To analyze the trend of antipsychotic drug consumption in Spain from
      1985 to 2000, and the impact of atypical antipsychotics on the overall
      consumption and on clozapine use. METHODS: Data on antipsychotic consumption were
      drawn from the ECOM database of the Spanish Ministry of Health, which contains
      the retail community pharmacies sales of medicinal products reimbursed by the
      National Health System. Data are presented as defined daily doses (DDDs) per 1000
      inhabitants per day, for each year. To evaluate the impact of atypical
      antipsychotics on clozapine use, data from the Spanish "Clozapine Monitoring
      Program" were analyzed. Consumption data from Nordic countries were obtained from
      national statistics. RESULTS: The use of antipsychotics in Spain increased
      progressively from 1.51 DDD/1000 inhabitants/d in 1985 to 5.73 DDD/1000
      inhabitants/d in 2000. The pattern of use of individual drugs changed greatly
      over the study period. In 1985, haloperidol, fluphenazine and thioridazine, all
      typical antipsychotics, were the drugs most widely used, whereas in 2000, the
      three drugs most frequently used were risperidone, olanzapine and haloperidol.
      The introduction of olanzapine in December 1996 reduced the number of new
      treatments with clozapine to half. Antipsychotic use is still lower in Spain than
      in Nordic countries, despite the prevalence of schizophrenia being similar
      worldwide. CONCLUSIONS: Antipsychotic agent use in Spain has increased
      progressively since 1985, reducing the differences between Spain and other
      European countries (Nordic countries). Substantial differences in the pattern of
      drug use from 1985 to 2000 have been observed.

PMID- 12504265
TI  - Criterion validity of the interpersonal dependency inventory: a preliminary study
      on 621 addictive subjects.
AB  - The interpersonal dependency inventory comprised three subscales called Emotional
      reliance of another person (ER), lack of social self confidence (LSS) and
      Assertion of autonomy (AUT). Several formula have been developed for deriving
      whole-scale scores. The aim of the study on 621 addictive subjects was to
      determine the best formula using the DSM-IV dependent personality disorder as
      gold standard. The formula 3 ER + LSS - AUT yielded the best values of
      sensitivity and specificity.

PMID- 12504266
TI  - Screening for domestic violence among patients admitted to a French emergency
      service.
AB  - OBJECTIVE: The authors assessed the prevalence of domestic violence among
      patients examined in the emergency service of a general hospital. They compared
      the socio-demographic status and psychiatric comorbidity of victims of domestic
      violence and other patients. METHOD: An assessment was made on 126 consecutive
      patients received by the emergency service of Bichat-Claude Bernard hospital
      (Paris, France). Assessment of domestic violence was made through the use of a
      specific questionnaire. RESULTS: The prevalence rate of domestic violence was 18%
      among patients examined by the emergency service. Thirty-five percent of the
      cases were physical violence, 22% sexual violence, 17% psychological violence and
      26% multiple forms of domestic violence. Domestic violence had been going on for
      less than 1 month in only one case. In 74% of the cases, violence lasted for more
      than 1 year. No differences were found in terms of socio-demographic
      characteristics (age, marital status, rate of unemployment, sex ratio) and
      psychiatric comorbidity between victims of domestic violence and others.
      CONCLUSION: Patients seen in an emergency service must be identified as a
      population at risk for domestic violence (18%). These situations can be
      identified only by a systematic assessment using a standardized questionnaire.

PMID- 12504267
TI  - Combination of clozapine and maprotiline in refractory psychotic depression.

PMID- 12504268
TI  - Arginine and immunity: a unique perspective.
AB  - Arginine functions in the body as a free amino acid, a component of most
      proteins, and the substrate for several non-protein, nitrogen-containing
      compounds, many of which function in immunity. Although arginine is synthesized
      in the body, it is not made in sufficient quantities to support growth or meet
      metabolic requirements during periods of stress. Based on the biochemical and
      physiological role of arginine in maintaining health and immunity, arginine is
      being added at pharmacologic concentrations to enteral formulas to boost immune
      function. Unfortunately, animal and human studies that investigate enteral
      arginine supplementation as the single variable do not show clear immunologic
      benefit. The inconsistent effects of arginine supplementation on immune function
      are due to numerous factors, such as the amount and timing of arginine
      supplementation, the animal species or strain of species, and the experimental
      model. Systematic study is required to determine whether a basal dietary intake
      of arginine is required to maintain immune function during health and how much
      arginine is required to meet metabolic requirements during periods of growth or
      stress.

PMID- 12504269
TI  - Cardiac surgery: myocardial energy balance, antioxidant status and endothelial
      function after ischemia-reperfusion.
AB  - Myocardial and endothelial damage is still a widely debated problem during the
      ischemia-reperfusion sequence in heart surgery. We evaluated myocardial purine
      metabolites, antioxidant defense mechanisms, oxidative status and endothelial
      dysfunction markers in 14 patients undergoing coronary artery by-pass graft
      (CABG). Heart biopsies were taken before aortic cross-clamping (t1), before clamp
      removal (t2) and 30 min after reperfusion (t3); perchloric extracts of the tissue
      were analyzed for glutathione, NAD, nucleotide nucleoside and base content by
      capillary electrophoresis (CE). In plasma samples from the coronary sinus we
      evaluated: nitrate and nitrite concentrations by CE, plasma glutathione
      peroxidase (plGPx) by ELISA, endothelin-1 (ET-1) by RIA and reactive oxygen
      metabolites (ROM) by colorimetric assay. During the ischemic period (t2) we
      observed a reduction in cellular NAD and GSH levels, as well as nitrate, nitrite
      and plGPx. ATP and GTP levels decreased and their catabolic products AMP, GMP,
      IMP, adenosine, inosine and hypoxanthine accumulated. The energy charge, ATP/ADP
      ratio, and nucleotide/(nucleoside + base) ratios decreased. At t3, levels of
      plasma ET-1 increased and monophosphate nucleotides tended to return to basal
      values. The energy charge did not increase but the nucleotide/(nucleoside +
      nucleobase) ratio recovered to some extent. Levels of nitrates plus nitrites
      continued to decrease. No significant variation in ROM levels was observed. Our
      data indicate that oxidative stress and endothelial damage are major events
      during CABG, overwhelming the scavenging capacity of the myocyte and preventing
      restoration of the normal energy balance for 30 min after reperfusion. The AMP
      deaminase pathway leading to IMP production is active during ischemia and
      adenosine is not the main compound derived from ATP break-down in the human
      heart. The possible role of extracorporeal circulation is also discussed.

PMID- 12504270
TI  - L-arginine and L-lysine stimulation on cultured human osteoblasts.
AB  - Essential amino acids, such as L-Arginine (Arg) and L-Lysine (Lys), are involved
      in bone metabolism and growth. Our previous studies analyzed the effect of these
      amino acids on rat osteoblast cultures and in experimental animals. In this
      study, we evaluated the effect of L-Arg and L-Lys on cultured human osteoblasts.
      Primary human osteoblast cultures were divided into four groups: the Arg Group
      received 0.625 mg/ml per day of Arg, the Lys Group 0.587 mg/ml per day of Lys,
      the Arg-Lys Group received both amino acids, whereas the Control Group was sham
      treated. After 7 days, the following parameters were tested in all groups:
      alkaline phosphatase (ALP), nitric oxide (NO), calcium (Ca), phosphorus (P),
      osteocalcin (OC), type I collagen (PICP), interleukin-6 (IL-6), transforming
      growth factor-beta 1 (TGF-beta 1) on culture supernatant, platelet derived growth
      factor (PDGF), insulin-like growth factor-I (IGF-I), and MTT proliferation test
      on cells. Arg administration significantly increased ALP, NO, PICP and IGF-I
      production and reduced the level of IL-6. Lys administration over the same time
      interval mainly affected cell proliferation, as evidenced by the MTT test and
      immunostaining for PDGF. The same positive effects evidenced by the single
      administrations of the two amino acids resulted from their simultaneous
      administration. However, synergism could be demonstrated only for the decrease in
      the level of IL-6. Arg and Lys show a positive effect on human osteoblasts, which
      is related partly to the production of those factors required for matrix
      synthesis, and partly to the direct or mediated activation of cell proliferation.

PMID- 12504271
TI  - Physiological parameters and biodistribution of 5,10,15,20-tetra (4
      methoxyphenyl) porphyrin in rats.
AB  - Physiological parameters on hepatic and renal functionality and biodistribution,
      accumulation and elimination, in different organs of the 5,10,15,20-tetra (4
      methoxyphenyl) porphyrin (TMP) were determined in Wistar rats. The transport of
      TMP by low-density (LDL) and high-density lipoproteins (HDL) was also
      investigated. The photosensitizer is accumulated in the spleen, where its
      concentration is significantly increased 21 d post-injection; it also accumulates
      in the liver and in a lower proportion, in the duodenum, and poorly in brain and
      muscle. The urine and serum biochemical parameters reached normal values both in
      control and treated groups. The glomerular filtrate rate was not affected by the
      TMP treatment in any of the studied times. These results would indicate that the
      sensitizer does not modify the renal glomerular function. TMP is mainly
      eliminated from the organism via the bile-gut pathway. Considering the total
      amount of porphyrin bound to both lipoproteins (LDL and HDL) in comparison with
      the total value of the TMP in serum, it can be inferred that a large amount of
      the agent is transported by lipoproteins in the plasma. This study proves
      information about the behavior of TMP in vivo under dark conditions. The results
      can be used to design photodynamic treatments using this porphyrin model as the
      sensitizer.

PMID- 12504272
TI  - The chitinase system from Trichomonas vaginalis as a potential target for
      antimicrobial therapy of urogenital trichomoniasis.
AB  - Chitinolytic activities in Trichomonas vaginalis membrane extracts were assessed
      by assays of three enzyme systems: N-acetyl-beta-D-hexosaminidase (NAHase),
      chitobiosidase and chitotriosidase. N-acetyl-beta-D-hexosaminidase was the enzyme
      that showed the highest specific activity. After successive subcutaneous
      inoculations into mice and parasite recovery in culture, the enzyme activities
      increased significantly with the number of inoculations for up to eight passages.
      In addition, enzyme activities were maximum at the logarithmic phase of growth.
      Glycol chitin, a chitinase substrate, enhanced all chitinolytic activities by
      about 30% and a clear-cut correlation is shown between the capacity for
      erythrocyte lysis by parasites and NAHase expression. Chitobiosidase and
      chitotriosidase activities were both inhibited at 58% and 100%, respectively, by
      allosamidine, a chitinase inhibitor used at 3 microM, whereas NAHase activity was
      not affected. Seven putative NAHase inhibitors (compounds n, 1-7), ureido and
      thioureido derivatives of 2-amino-2-deoxy-D-glucose were evaluated and five of
      them had K(i) values in the range 30-70 microM. The most active compound
      (compound 6) was functionally competitive with respect to the substrate with a
      K(i) value of 30 microM. The IC(50) values of the most active compounds on T.
      vaginalis were in the range 62-85 microM. These results indicate that chitinases
      of T. vaginalis are involved in pathogenicity and they could be an interesting
      target for drugs since chitinase inhibitors also inhibit parasite growth.

PMID- 12504277
TI  - Changes in IGF-I receptor and IGF-I mRNA during differentiation of 3T3-L1
      preadipocytes.
AB  - Insulin-like growth factor-1 (IGF-I) is an essential factor for the
      differentiation of preadipocytes into adipocytes. We investigated the expression
      of IGF-I receptor and IGF-I RNA messenger during 3T3-L1 preadipocyte
      differentiation. Levels of IGF-I receptor decreased in the mature adipocytes
      compared to cells before the initiation of differentiation. In addition, cultures
      not induced to differentiate showed a decrease on the receptor levels after 4
      days in the presence of insulin compared to cultures without treatment. The
      levels of the IGF-I RNA messenger were shown to be higher in mature adipocytes
      compared to preadipocytes. We propose an autocrine and/or paracrine action of IGF
      I in this adipocyte differentiation model, where IGF-I produced by the
      differentiating preadipocytes acts over their adjacent cells and, in this way,
      diminishes the expression of IGF-I receptor.

PMID- 12504278
TI  - Kinetic properties of rrn promoters in Escherichia coli.
AB  - How do bacteria adapt and optimize their growth in response to different
      environments? The answer to this question is intimately related to the control of
      ribosome bio-synthesis. During the last decades numerous proposals have been made
      to explain this control but none has been definitive. To readdress the problem,
      we have used measurements of rRNA synthesis rates and rrn gene dosages in E. coli
      to find the absolute transcription rates of the average rrn operon (transcripts
      per min per operon) at different growth rates. By combining these rates with lacZ
      expression data from rRNA promoter-lacZ fusions, the abolute activities of the
      isolated rrnB P1 and P2 promoters were determined as functions of the growth rate
      in the presence and absence of Fis and of the effector ppGpp. The promoter
      activity data were analyzed to obtain the relative concentrations of free RNA
      polymerase, [R(f)], and the ratio of the Michaelis-Menten parameters, V(max)/K(m)
      (promoter strength), that characterize the promoter-RNA polymerase interaction.
      The results indicate that changes in the basal concentration of ppGpp can account
      for all growth-medium dependent regulation of the rrn P1 promoter strength. The
      P1 promoter strength was maximal when Fis was present and the level of ppGpp was
      undetectable during growth in rich media or in ppGpp-deficient strains; this
      maximal strength was 3-fold reduced when Fis was removed and the level of ppGpp
      remained undetectable. At ppGpp levels above 55 pmol per cell mass unit (OD(460))
      during growth in poor media, the P1 promoter strength was minimal and not
      affected by the presence or absence of fis. The half-maximal value occurred at 20
      pmol ppGpp/OD(460) and corresponds to an intracellular concentration of about 50
      microM. In connection with previously published data, the results suggest that
      ppGpp reduces the P1 promoter strength directly, by binding RNA polymerase, and
      indirectly, by inhibiting the synthesis of Fis.

PMID- 12504279
TI  - Limited utility of blue fluorescent protein (BFP) in monitoring plant virus
      movement.
AB  - While the green fluorescent protein (GFP) is a routinely used marker gene in
      higher plants, there are only a few data concerning the use of blue fluorescent
      protein (BFP). These proteins together are used for dual colour tagging
      experiments in various biological systems; however, the benefits of this
      technique in plant virology have not been exploited yet. In this work, our aim
      was to determine whether the BFP is a suitable second marker in conjunction with
      GFP for following the progress of virus infection. Nicotiana clevelandii, N.
      benthamiana and N. tabacum cv. Xanthi-nc plants were infected with potato virus X
      vector carrying the GFP or the Y66H type BFP gene. While GFP was brightly
      fluorescent in all species, the fluorescence intensity of BFP varied widely, from
      the bright fluorescence observed in N. clevelandii to the absence of fluorescence
      in N. tabacum cv. Xanthi-nc. Since at even mild acidic pH BFP rapidly fades, the
      more acidic cytosol of N. tabacum could be responsible for impaired in vivo
      fluorescence. After infiltration of the infected leaves of N. clevelandii with pH
      5 phosphate buffer, the fluorescence faded thus confirming this situation.

PMID- 12504280
TI  - Pyruvate reverses metabolic effects produced by hypoxia in glioma and hepatoma
      cell cultures.
AB  - The intervention of pyruvate in glucose metabolism was investigated during
      hypoxic stress in tumour cell cultures having respiratory capacities under
      normoxic conditions. Results obtained with nuclear magnetic resonance (NMR)
      spectroscopy showed that, under normoxic conditions, rat glioma C6 and human
      hepatoma Hep G2 cell cultures metabolised [(13)C(1)]glucose into lactate,
      alanine, glutamate and other less abundant metabolites, as already known from the
      literature. In the absence of pyruvate, during hypoxia or cyanide poisoning, both
      cell types dramatically decreased the label into glutamate and accumulated
      [(13)C(3)]glycerol-3-phosphate. The compound was further identified by 31P NMR
      spectroscopy. The accumulation of the label in glycerol-3-phosphate, however, did
      not occur when the cells were incubated in the presence of pyruvate. The fate of
      the latter, followed under normoxic conditions by incubating cells with
      [(13)C(3)]pyruvate and natural glucose, showed that the label was mainly found in
      alanine, lactate and glutamate. Anoxic conditions increased the label in lactate
      and reduced that of glutamate. The data show a metabolic effect of pyruvate
      during mitochondrial blockade due to severe lack of oxygen in tumour cell lines.

PMID- 12504281
TI  - Peroxynitrite-induced inhibition and nitration of cardiac myofibrillar creatine
      kinase.
AB  - Although cardiac peroxynitrite formation and attendant protein nitration is an
      established event in both acute and chronic settings of cardiac failure, the
      putative intracellular targets involved remain incompletely defined. We have
      recently shown that the myofibrillar isoform of creatine kinase (a critical
      energetic controller of cardiomyocyte contractility) may be a particularly
      sensitive target of peroxynitrite-induced nitration and inactivation in vivo.
      However, the kinetic and mechanistic aspects of this interaction remain
      undefined. Here we tested the hypothesis that myofibrillar creatine kinase is
      sensitive to inhibition by peroxynitrite, and investigated the mechanistic role
      for tyrosine nitration in this process. Peroxynitrite potently and irreversibly
      inhibited myofibrillar creatine kinase capacity (Vmax), at concentrations as low
      as 100 nM, while substrate affinity (Km) was unaffected. Concentration-dependent
      nitration of myofibrillar creatine kinase was observed. The extent of nitration
      was linearly related to peroxynitrite concentration and highly correlated to the
      extent of myofibrillar creatine kinase inhibition. This inhibition was not
      reversible by treatment with free cysteine (250 microM), but pre-incubation with
      substrate (phosphocreatine and/or ATP) provided significant protection of MM-CK
      from both nitration and inhibition. These results suggest that myofibrillar
      creatine kinase is a highly sensitive target of peroxynitrite-mediated
      inhibition, and that nitration may mediate this inhibition.

PMID- 12504282
TI  - Identification of the cofilin-binding sites in the large cytoplasmic domain of
      Na,K-ATPase.
AB  - Na,K-ATPase, an alpha, beta heterodimer, is found in the plasma membrane of all
      animal cells. The alpha chain is believed to have 10 transmembrane regions and a
      large cytoplasmic domain between the 4th and 5th transmembrane regions (H4-H5).
      In our previous report, the large (3rd) cytoplasmic domains of the alpha1 and
      alpha2 isoform were found to interact with cofilin, an actin-modulating protein,
      by the yeast two-hybrid system. Here we show that cofilin interacts only with the
      3rd cytoplasmic domain of the alpha2 subunit but not with the 2nd, 4th, and 5th
      cytoplasmic domains or the cytoplasmic region of the beta subunit of Na,K-ATPase.
      We also demonstrate that cofilin interacts with the large cytoplasmic domains of
      the alpha1, alpha2 and alpha3 isoforms of Na,K-ATPase, but not with those of
      glucose transporter 1, glucose transporter 4, cystic fibrosis transmembrane
      conductance regulator and plasma membrane Ca-ATPase. We introduced 10 mutations
      into the 3rd cytoplasmic domain of Na,K-ATPase to identify the binding sites with
      cofilin. Eight of these mutants were single amino acid substitutions (R417Q,
      K470Q, K654G, D672A, K691A, R700G, R700A and D710G) and two were double mutant
      (K654GR700G and K719AK720A). Analysis of the activity of the reporter gene of
      these mutants shows that residues D672 and R700 of the 3rd cytoplasmic domain of
      Na,K-ATPase are involved in the interaction with cofilin.

PMID- 12504283
TI  - Changes during hibernation in different phospholipid and free and esterified
      cholesterol serum levels in black bears.
AB  - During hibernation, fat is known to be the preferred source of energy. A detailed
      analysis of different phospholipids, as well as free and esterified cholesterol,
      was conducted to investigate lipid abnormalities during hibernation. The levels
      of total phospholipids and total cholesterol in the serum of black bears were
      found to increase significantly in hibernation as compared with the active state.
      Both free and esterified cholesterol were increased in the hibernating state in
      comparison with the active state (P < 0.05). The percentage increase during
      hibernation was more in free cholesterol (57%) than in esterified cholesterol
      (27%). Analysis of subclasses of serum phospholipids showed that choline
      containing phospholipids, i.e., sphingomyelin (SPG) (14%) and phosphatidylcholine
      (PC) (76%), are the major phospholipids in the serum of bear. The minor
      phospholipids included 8% of phosphatidylserine (PS) + phosphatidylinositol (PI),
      while phosphatidylethanolamine (PE) was only 2% of the total phospholipids. A
      comparison of phospholipid subclasses showed that PC, PS + PI and SPG were
      significantly increased, while PE was significantly decreased (P < 0.05) in the
      hibernating state as compared with the active state in black bears. These results
      suggest that the catabolism of phospholipids and cholesterol is decreased during
      hibernation in black bears, leading to their increased levels in the hibernating
      state as compared with the active state. In summary, our results indicate that
      serum cholesterol and phospholipid fractions (except PE) are increased during
      hibernation in bears. It is proposed that the increase of these lipids may be due
      to the altered metabolism of lipoproteins that are responsible for the clearance
      of the lipids.

PMID- 12504284
TI  - Purification, some properties of a D-galactose-binding leaf lectin from Erythrina
      indica and further characterization of seed lectin.
AB  - Lectin from a leaf of Erythrina indica was isolated by affinity chromatography on
      Lactamyl-Seralose 4B. Lectin gave a single band in polyacrylamide gel
      electrophoresis (PAGE). In SDS-gel electrophoresis under reducing and non
      reducing conditions Erythrina indica leaf lectin (EiLL) split into two bands with
      subunit molecular weights of 30 and 33 kDa, whereas 58 kDa was obtained for the
      intact lectin by gel filtration on Sephadex G-100. EiLL agglutinated all human
      RBC types, with a slight preference for the O blood group. Lectin was found to be
      a glycoprotein with a neutral sugar content of 9.5%. The carbohydrate specificity
      of lectin was directed towards D-galactose and its derivatives with pronounced
      preference for lactose. EiLL had pH optima at pH 7.0; above and below this pH
      lectin lost sugar-binding capability rapidly. Lectin showed broad temperature
      optima from 25 to 50 degrees C; however, at 55 degrees C EiLL lost more than 90%
      of its activity and at 60 degrees C it was totally inactivated. The pI of EiLL
      was found to be 7.6. The amino acid analysis of EiLL indicated that the lectin
      was rich in acidic as well as hydrophobic amino acids and totally lacked cysteine
      and methionine. The N-terminal amino acids were Val-Glu-Thr-IIe-Ser-Phe-Ser-Phe
      Ser-Glu-Phe-Glu-Ala-Gly-Asn-Asp-X-Leu-Thr-Gln-Glu-Gly-Ala-Ala-Leu-. Chemical
      modification studies of both EiLL and Erythrina indica seed lectin (EiSL) with
      phenylglyoxal, DEP and DTNB revealed an absence of arginine, histidine and
      cysteine, respectively, in or near the ligand-binding site of both lectins.
      Modification of tyrosine with NAI led to partial inactivation of EiLL and EiSL;
      however, total inactivation was observed upon NBS-modification of two tryptophan
      residues in EiSL. Despite the apparent importance of these tryptophan residues
      for lectin activity they did not seem to have a direct role in binding haptenic
      sugar as D-galactose did not protect lectin from inactivation by NBS.

PMID- 12504286
TI  - Interhemispheric intracranial pressure gradients in nonhuman primate stroke.
AB  - BACKGROUND: Although the development of significant interhemispheric intracranial
      pressure (ICP) gradients in the setting of unilateral stroke remains
      controversial, no study to date has investigated the existence of these gradients
      in a controlled, reproducible, clinically relevant model. Therefore, we used a
      primate model of reperfused hemispheric stroke to better characterize the
      development of these gradients. METHODS: Bilateral intraparenchymal ICP was
      continuously monitored in 7 adult male baboons subjected to left hemisphere
      reperfused stroke. Interhemispheric ICP gradients were calculated for each baboon
      and plotted over time. Infarct volume was determined using T2-weighted magnetic
      resonance imaging (MRI) at sacrifice. RESULTS: A bimodal distribution of
      interhemispheric ICP gradients was observed in animals with >20% infarct volume
      (22.1% +/- 0.9; range 21-23%) versus < or = 15% infarct volume (6.6% +/- 2.7;
      range 1-15%). In animals with >20% infarct volume, interhemispheric gradients
      developed early and persisted throughout the monitoring period. At 12 hours
      postreperfusion, animals with large infarcts demonstrated a mean pressure
      gradient of 13.8 +/- 4.3 mm Hg, compared to a mean gradient of -2.6 +/- 1.1 mm Hg
      for animals with < or =15% infarct volume. The difference in pressure gradients
      was statistically significant at all time points from 4 to 12 hours
      postreperfusion (p < 0.01). CONCLUSIONS: These data suggest that, in nonhuman
      primates, infarcts of a size approaching 20% of the hemisphere may be associated
      with significant ICP gradients. With these larger infarcts, ipsilateral
      monitoring is required if regional cerebral perfusion pressure is to be
      accurately assessed.

PMID- 12504288
TI  - Preoperative assessment of motor cortex and pyramidal tracts in central cavernoma
      employing functional and diffusion-weighted magnetic resonance imaging.
AB  - BACKGROUND: Functional MRI (fMRI) combines anatomic with functional information
      and has therefore been widely used for preoperative planning of patients with
      mass lesions affecting functionally important brain regions. However, the courses
      of functionally important fiber tracts are not visualized. We therefore propose
      to combine fMRI with diffusion-weighted MRI (DWI) that allows visualization of
      large fiber tracts and to implement this data in a neuronavigation system.
      METHODS: DWI was successfully performed at a field strength of 1.5 Tesla,
      employing a spin-echo sequence with gradient sensitivity in six noncollinear
      directions to visualize the course of the pyramidal tracts, and was combined with
      echo-planar T2* fMRI during a hand motor task in a patient with central
      cavernoma. RESULTS: Fusion of both data sets allowed visualization of the
      displacement of both the primary sensorimotor area (M1) and its large descending
      fiber tracts. Intraoperatively, these data were used to aid in neuronavigation.
      Confirmation was obtained by intraoperative electrical stimulation. Postoperative
      MRI revealed an undisrupted pyramidal tract in the neurologically intact patient.
      CONCLUSION: The combination of fMRI with DWI allows for assessment of
      functionally important cortical areas and additional visualization of large fiber
      tracts. Information about the orientation of fiber tracts in normal appearing
      white matter in patients with tumors within the cortical motor system cannot be
      obtained by other functional or conventional imaging methods and is vital for
      reducing operative morbidity as the information about functional cortex. This
      technique might, therefore, have the prospect of guiding neurosurgical
      interventions, especially when linked to a neuronavigation system.

PMID- 12504291
TI  - Selective intraoperative angiography in intracranial aneurysm surgery:
      intraoperative factors associated with aneurysmal remnants and vessel occlusions.
AB  - BACKGROUND: The objective of this study was to assess the role of selective
      intraoperative angiography and to analyze the factors associated with faulty clip
      application. METHODS: Two hundred thirty-eight patients undergoing surgery for
      intracranial aneurysms were studied consecutively for intraoperative angiography
      (IOA)-related events. The procedure was performed in 155 operations. Demographic
      details, clinical grade of the patient, location and size of the aneurysm,
      intraoperative rupture, application of the temporary clip, IOA findings, and
      final outcome were analyzed. RESULTS: In the 155 patients in the series, there
      were 125 anterior circulation aneurysms and 30 on the vertebrobasilar system.
      Aneurysms were smaller than 10 mm in 63% of the patients, and 19 were giant
      aneurysms. Thirty-eight percent were unruptured, 36% were Hunt and Hess Grades I
      and II, 21% were Grade III, and 5% were Grades IV and V. An intraoperative
      rupture occurred in 18 operations. Intraoperative angiography was normal in 88%;
      in 11 cases (7%) there was a residual neck, and in 8 (5%), occlusion of the
      artery was observed. An incomplete clipping was significantly related to
      intraoperative rupture of the aneurysm (p < 0.008) and anterior location of the
      aneurysm (p = 0.05), whereas vessel occlusion had a significant association with
      posterior location of the aneurysm (p < 0.0005). An eventful IOA had significant
      association with poor outcome (p < 0.003). CONCLUSION: Intraoperative rupture and
      a posterior location of the aneurysm had a significant correlation with residual
      aneurysm and vessel occlusion, respectively. The use of IOA is justified in
      aneurysms associated with these factors.

PMID- 12504295
TI  - Sensitivity of scalp EEG, cortical EGG, and somatosensory evoked responses during
      surgery for intracranial aneurysms.
AB  - BACKGROUND: We estimated the relative sensitivity and reliability of scalp EEG,
      cortical EEG and somatosensory evoked potentials (SSEPs) to detect significant
      changes during aneurysm surgery. METHODS: Two observers independently reviewed
      data from 18 patients who were monitored with scalp EEG, cortical EEG, and SSEPs
      to determine which if any modality demonstrated significant changes during 25
      different episodes of temporary intracranial vascular occlusion. RESULTS: Kappa
      scores indicating the degree of agreement between the two observers were highest
      for the cortical strip EEG (kappa = 0.92) and the SSEPs (kappa = 0.82) and much
      greater than for the scalp EEG data (kappa = -0.07). The cortical strip
      recordings showed changes more often than either the scalp EEG or SSEP during
      temporary vascular occlusion. In no case did the scalp EEG change when neither
      the strip nor SSEP changed. In only 4% of events did the observers feel that the
      SSEP changed when the strip did not, but in 16% of cases, the strip changed
      without changes in any of the other modalities. CONCLUSIONS: Recording of EEG
      from strip electrodes placed on the cortical surface detects changes more
      frequently than either scalp EEG or SSEPs during vascular occlusion. Different
      observers were more likely to agree on whether the cortical strip EEG changed
      during vascular occlusion than the other modalities. This argues for the possible
      advantages of recording from strip electrodes during aneurysm surgery.

PMID- 12504298
TI  - Unruptured carotid-duplicated middle cerebral artery aneurysm: case report.
AB  - We demonstrate the first case with unruptured carotid-duplicated middle cerebral
      artery (IC-Dup MCA) aneurysm combined with ruptured opposite carotid aneurysm.
      Eleven IC-Dup MCA aneurysm reported until now had all ruptured. It is noteworthy
      that 8 patients of the 11 were Japanese.

PMID- 12504299
TI  - Traumatic middle meningeal artery pseudoaneurysm and subsequent fistula formation
      with the cavernous sinus: case report.
AB  - BACKGROUND: A combination of pseudoaneurysm and arteriovenous fistula of the
      middle meningeal artery is rare. We describe a case of traumatic pseudoaneurysm
      of the middle meningeal artery, which subsequently formed a fistula with the
      cavernous sinus. CASE DESCRIPTION: A 23-year-old man suffered from blunt head
      trauma and skull fractures. Sixteen days later, he suddenly experienced headache
      and a bruit was auscultated over the left ear. Three-dimensional computed
      tomographic angiography revealed dilatation of the left middle meningeal artery.
      The dilation proved to be a pseudoaneurysm on cerebral angiograms and it was also
      found to have formed a fistula with the cavernous sinus. Both lesions were
      successfully obliterated by endovascular embolization using microcoils.
      CONCLUSION: Head injury may lead to asymptomatic pseudoaneurysm or dural
      arteriovenous fistula. Neurosurgeons should always bear in mind the possibility
      of such vascular injuries after blunt head trauma to prevent any hemorrhagic
      complications.

PMID- 12504300
TI  - Transdural metastasis from adenocarcinoma of the prostate mimicking subdural
      hematoma: case report.
AB  - BACKGROUND: Metastasis of prostatic adenocarcinoma to the nervous system is
      extremely rare and has been infrequently reported over the last several years. We
      describe the presentation, evaluation, and surgical intervention of a case of
      metastatic prostate carcinoma to the dura. CASE DESCRIPTION: This patient
      presented with symptoms and physical findings consistent with a subacute subdural
      hematoma in the setting of recently diagnosed adenocarcinoma of the prostate. He
      underwent a craniotomy for presumed subdural hematoma. The pathologic diagnosis
      was consistent with metastatic prostatic carcinoma. CONCLUSION: This case report
      demonstrates the need for broad differential diagnosis in the evaluation and
      treatment of patients presenting with seemingly straightforward subacute subdural
      hematomas.

PMID- 12504302
TI  - Brain metastases from asymptomatic adenocarcinoma of the pancreas: an autopsy
      case report.
AB  - BACKGROUND: Brain metastasis from pancreatic cancer is extremely rare. Because
      pancreatic cancer usually has a rapidly progressive nature, the majority of
      affected patients die from primary lesions before exhibiting clinical signs
      suggestive of brain metastases. CASE DESCRIPTION: The patient was a 62-year-old
      man who developed generalized convulsion followed by right hemiparesis
      accompanied by decreased consciousness level. Computed tomography (CT) scan
      revealed multiple brain tumors with ring-like contrast enhancement. Stereotactic
      biopsy disclosed mucinous adenocarcinoma. A marked increase in the serum CA19-9
      level was noted, but the patient did not exhibit any other signs of pancreatic
      disease. Repeated whole body CT scan and ultrasonography demonstrated no primary
      lesions. The patient died of multi-organ failure during chemotherapy combined
      with radiation for metastatic brain tumors. Autopsy revealed well-differentiated
      papillary adenocarcinoma in the pancreatic head and systemic metastases
      associated with tumor emboli were widely distributed in various organs.
      CONCLUSION: This patient initially presented only with symptoms of neurologic
      disorder and no pancreatic symptoms. Moreover, repeated radiologic examinations
      did not reveal the primary lesion. We considered that the unusual clinical course
      in our patient may be partly explained by the autopsy findings: diffuse sclerotic
      changes of the pancreas without swelling. The present report suggests that
      undetected pancreatic cancer may have been the primary lesion classified as
      "unknown origin" in some cases of metastatic brain tumors.

PMID- 12504304
TI  - Multiple subpial lipomas with dumb-bell extradural extension through the
      intervertebral foramen without spinal dysraphism.
AB  - BACKGROUND: Intradural subpial lipomas not associated with spinal dysraphism,
      account for less than 1% of spinal cord tumors. The simultaneous existence of
      multiple intradural subpial lipomas with dumb-bell extradural extension through
      the intervertebral foramen in the same patient without any evidence of spinal
      dysraphism has not been previously reported. CASE DESCRIPTION: A 38-year-old man
      presented with progressive spastic paraparesis, and weakness of right elbow
      extension and opposition of the medial three fingers. He also had ascending
      paraesthesia from the C6 dermatome to the saddle region and loss of joint and
      position sense of both lower limbs with hesitancy and precipitancy of
      micturition. There was no spinal tenderness, deformity, neurocutaneous markers,
      or spinal dysraphism. The total duration of illness was 11 years. The oblique
      views of the plain radiographs of the cervical spine revealed an enlarged right
      C7-D1 intervertebral foramen. The T1- and T2-weighted magnetic resonance (MR)
      images showed two intradural, hyperintense lesions (with extensive loss of signal
      on fat suppression sequences), one extending from C5 to D2 and the other opposite
      the C3-4 disc space. The parasagittal and axial images showed the extradural
      component of the lesion emerging from the right C7-D1 intervertebral foramen. At
      surgery, a C2 to D2 laminectomy was performed. The lipoma, enclosed in a fine
      pial membrane, was situated on the right posterolateral aspect of the cord. The
      right-sided nerve roots from the C6 to D1 levels were completely enmeshed by the
      lipoma. There was a separate superficial subpial lipoma adherent to the posterior
      aspect of the cord at the C3-4 level. A distinct area of normal cord was present
      between the two lesions. A subtotal decompression of the lesions including the
      component emerging through the right C7-D1 intervertebral foramen and a
      duraplasty were performed. At follow-up after 18 months, the posterior column
      impairment, lower limb hypoaesthesia, and right upper limb paraesthesia had
      improved. However, residual elbow extension and lower limb weakness, mild lower
      limb spasticity and sphincteric dysfunction persisted. CONCLUSIONS: The
      multiplicity of intradural subpial lipomas without spinal dysraphism points to a
      dysembryogenetic basis similar to that seen in patients with spinal dysraphism
      that results in lipomas, but in which the defect is not severe enough to give
      rise to coexisting vertebral and soft tissue anomalies. The dumb-bell extradural
      extension through the intervertebral foramen is extremely rare. The magnetic
      resonance imaging and surgical principles are discussed.

PMID- 12504307
TI  - Tilting operating table with self-control foot switch: a new neurosurgical tool.
AB  - BACKGROUND: Observation of the surgical field from all directions is essential in
      microneurosurgery. A tilting operating table operated by the surgeon can satisfy
      this need. METHODS: A tilting operating table operated by the surgeon using a
      foot switch was developed by modifying the Sugita table incorporating the X-Y
      shifter. RESULTS AND CONCLUSIONS: The modified operating table allows the surgeon
      to move the patient in the head up or down directions, as well as the left side
      down or right side down directions, so the surgical field can be inspected from
      all aspects without changing the vertical axis of the operating microscope.

PMID- 12504308
TI  - Skin markers for surgical planning for intradural lesions of the thoracic spine.
      Technical note.
AB  - BACKGROUND: Preparation for surgery for thoracic intraspinal lesions commonly
      involves rather difficult X-ray procedures in the operating room. The object of
      this report is to inform neurosurgeons about a modified technique for
      preoperative surface localization of intraspinal thoracic pathology. METHODS:
      Adhesive, disposable radiographic skin markers placed at the presumed level of an
      intraspinal lesion are visualized along with the lesion on sagittal magnetic
      resonance scans of the thoracic spine. RESULTS: The lesion and the skin markers
      were clearly identified within the same field of view. The lesion itself rather
      than the vertebral body becomes the reference point for localization. CONCLUSION:
      Preoperative imaging with adhesive skin markers facilitates positioning and
      draping for surgery for thoracic intraspinal lesions. It may even replace intra
      operative X-ray procedures in selected cases.

PMID- 12504309
TI  - Practice patterns in the U.S.

PMID- 12504310
TI  - Intraoperative angiography for intracranial aneurysm surgery: what it really
      means.

PMID- 12504311
TI  - Chiari III malformation: varieties of MRI appearances in two patients.
AB  - Chiari III malformation is an extremely rare anomaly, which is characterized by
      the herniation of posterior fossa contents, i.e., cerebellum, brain stem and
      fourth ventricle, and in some cases upper cervical spinal cord through a low
      occipital and/or upper cervical osseous defect. We report different presentations
      of Chiari III malformation in two unusual cases to show the diversity of imaging
      findings of this rare malformation.

PMID- 12504312
TI  - Diffusion-weighted images in children with meningoencephalitis.
AB  - PURPOSE: The objective of the study was to evaluate the maps of apparent
      diffusion coefficients (ADCs) and diffusion-weighted (DW) images in demonstrating
      meningoencephalitic lesions in children. MATERIALS AND METHODS: Between May 1998
      and May 2000, 18 infants and children (4.5-190 months old) suffering from
      meningoencephalitis were included in the study. The diagnoses were bacterial
      meningoencephalitis in 8 and aseptic or viral in 10 patients. All 18 patients had
      brain MRI examinations. In the axial plane, three pulse sequences were performed
      on all patients: (1) FSE T2W images; (2) fast FLAIR images; (3) single-shot
      echoplanar DW images were acquired. Another 18 patients from the control group
      also received DW image examination. ADCs were computed for all regions on each DW
      image. RESULTS: The absolute values of CNRs of lesions on T2W (7.27+/-5.51),
      FLAIR (5.56+/-5.03) and DW (13.36+/-16.64) images were significantly greater than
      those on ADC maps (0.42+/-0.30) in the study group of patients (P<.01). In
      addition, absolute CNRs on DW images were significantly greater than on T2W and
      FLAIR images (P<.01). However, lesions on ADC maps in the study group have
      significantly greater CNRs than in the control group (0.13+/-0.12) (P<.01). CNRs
      on initial DW images from patients with atrophy or swelling of
      meningoencephalitic lesions were significantly different from the CNRs of those
      patients without significant changes in meningoencephalitic lesions (P=.02<.05).
      CONCLUSION: The DW image is a sensitive tool for detecting meningoencephalitic
      lesions and is better than FSE T2W and fast FLAIR images in CNRs. Diffusion MR
      techniques provides new ways to possibly predict the outcome of intracranial
      infectious diseases in children.

PMID- 12504313
TI  - Prominent myelin vacuolization in neurofibromatosis type 2.
AB  - Myelin vacuolization has previously been documented by MRI with histopathologic
      correlation in patients with neurofibromatosis type 1. This paper presents a
      patient with neurofibromatosis type 2 with MRI findings consistent with a
      prominent form of myelin vacuolization, unilaterally involving the right
      thalamus, globus pallidus and substantia nigra. On MRI, they appeared as multiple
      nodular-ovoid structures with a layered configuration. They were hypointense on
      T1-weighted, and FLAIR images, and hyperintense on T2-weighted images. On the
      apparent diffusion coefficient (ADC) map of an echo-planar diffusion imaging
      sequence, their ADC value ranged between 1.98 and 2.27x10(-3) mm(2)/s, a value
      higher than that of normal cerebral parenchyma, less than that of CSF.

PMID- 12504314
TI  - Subcortical gray matter N-acetylaspartate reduction in two cases of vascular
      dementia.
AB  - Many of the previous studies of vascular dementia using proton magnetic resonance
      (MR) spectroscopy had been carried out on white matter. However, no proton
      spectroscopic data of the subcortical gray matter are available in such disease.
      We report two cases suffering from vascular dementia, with an unilateral N
      acetylaspartate (NAA) decrease on subcortical gray matter. This significant
      reduction in NAA ratios was associated with an increase of choline on the
      ipsilateral centrum semiovale. We discuss the pathophysiology of these cases.

PMID- 12504315
TI  - Suprasellar hemangioblastoma in Von Hippel-Lindau disease: a case report.
AB  - Hemangioblastomas of the sellar and suprasellar regions are extremely rare
      lesions. We present a case of a suprasellar hemangioblastoma occurring in a 40
      year-old female with Von Hippel-Lindau disease.

PMID- 12504316
TI  - Femoral-facial syndrome with malformations in the central nervous system.
AB  - The femoral hypoplasia-unusual facies syndrome (FFS) is a very rare association
      of femoral and facial abnormalities. Maternal diabetes mellitus has been mainly
      involved as the causal agent. We report the second case of FFS with anomalies in
      the central nervous system (CNS) including corticosubcortical atrophy,
      colpocephaly, partial agenesis of corpus callosum, hypoplasia of the falx cerebri
      and absent septum pellucidum. The psychomotor development has been normal. We
      propose that the CNS defects observed in these patients are part of the spectrum
      of abnormalities in the FFS.

PMID- 12504317
TI  - MRI appearance of giant cell tumor of the lateral skull base: a case report.
AB  - The giant cell tumor is considered to be a locally aggressive benign tumor and
      has a low tendency toward distant metastasis. They are primarily present in the
      long bone and are rare in the skull. The osteoclast-like giant cells do not
      demonstrate mitotic activity and contain large numbers of nuclei. Herein, we
      described a case of giant cell tumor in the temporal lobe. Heterogenous
      enhancement is shown on CT imaging in solid areas of tumor. The appearance
      intermediate to high signal intensity on T1-weighted and very low signal
      intensity on T2-weighted MR imaging were due to the presence of hemosiderin from
      prior hemorrhage.

PMID- 12504318
TI  - Nodular fasciitis of the head and neck: radiographic findings.
AB  - Nodular fasciitis is an unusual benign reactive process of the soft tissues
      related to the fascia and characterized by fibroblastic proliferation. Clinical
      findings and radiologic aspects of six cases are described [four computed
      tomography (CT), two ultrasonography (US), one magnetic resonance (MR)]. They
      were located in the infrahyoid anterior triangle (n=3), prevertebral space (n=2),
      and masticator space (n=1). Most of these lesions showed moderate to strong
      enhancement on CT or MR imaging, and were partially embedded in the adjacent
      muscle with preservation of smooth margin of the muscle. Most cases showed a
      benign nature, except one case in the prevertebral space which showed aggressive
      nature with jugular fossa destruction and intracranial extension.

PMID- 12504319
TI  - Primary sphenoid esthesioneuroblastoma studied with MR.
AB  - Esthesioneuroblastoma (ENB) is an uncommon tumor type of neural crest origin,
      which, in the majority of cases, arises in the nasal cavity. We present a rare
      primary presentation of ENB in the sphenoidal area studied with computed
      tomography (CT) and magnetic resonance (MR). To our knowledge, this is the first
      case in which MR findings are available.

PMID- 12504320
TI  - Diastematomyelia with terminal lipomyelocystocele arising from one hemicord: case
      report.
AB  - Diastematomyelia is an uncommon spinal dysraphism with midline dorsoventral
      clefting of the spinal cord. Formation of syrinx cavity within the hemicord,
      vertebral anomalies and lipomas is known to be associated with diastematomyelia.
      We present an unusual case of a 4-month-old girl, who presented with
      diastematomyelia and terminal myelocystocele, and dilatation of the terminal
      portion of the spinal canal with formation of a cystic structure. Findings were
      confirmed by subsequent surgery and histopathology. Ectopic right kidney, Chiari
      I malformation and changes of partial sacral agenesis were other findings noted
      in this case. No case report of formation of terminal myelocystocele arising from
      one hemicord was described in the literature we reviewed.

PMID- 12504321
TI  - Diagnosis and treatment of midline prostatic cysts.
AB  - We report three patients with midline prostatic cysts (simple, n=1; complex, n=2)
      that presented with low ejaculate volume and hematospermia. Transrectal
      ultrasound (TRUS) revealed a midline prostatic cystic structure that could
      represent either an ejaculatory duct cyst or a Mullerian duct cyst. In one
      patient, the ejaculatory duct cyst was confirmed by identification of spermatozoa
      at microscopic analysis of fluid obtained by TRUS-guided needle aspiration. The
      two other patients underwent transurethral incision of the cyst with complete
      resolution of symptoms.

PMID- 12504322
TI  - Local staging of prostate cancer with endorectal surface coil MR imaging in a mid
      field magnetic system.
AB  - To investigate the accuracy of endorectal surface coil magnetic resonance imaging
      (ecMRI) in a 1.0-T magnetic field for the local staging of prostate cancer, 25
      patients were studied. In 14 Stages T1 and T2 tumors, 11 were correctly
      identified and 3 were overstaged. In 11 Stage T3 neoplasms, ecMRI was accurate in
      7 cases, and the other 4 were understaged. The overall accuracy of ecMRI in 1.0 T
      was 72% and that was comparable to the reported accuracy of this technique in
      high-field systems.

PMID- 12504323
TI  - Unusual manifestations of soft tissue metastasis.
AB  - We present a patient with pulmonary adenocarcinoma metastatic to the left
      forearm. The magnetic resonance imaging (MRI) revealed no discrete tumor, but an
      infiltrative signal change of the subcutaneous tissue and muscle. The lymphatic
      invasion by cancer cells explains this unusual manifestation of image findings.

PMID- 12504324
TI  - Initial experience using magnetic resonance imaging in prenatal diagnosis of
      osteogenesis imperfecta type II: a case report.
AB  - We report a fetus with osteogenesis imperfecta (OI) first diagnosed by ultrasound
      in routine prenatal examination and further evaluated by magnetic resonance
      imaging (MRI). Fetal MRI was undertaken with a 1.5-T magnet using a body-phased
      array coil and an ultrafast imaging technique, half-Fourier single-shot turbo
      spin-echo (HASTE). Radiological examination shortly after birth and postmortem
      examination confirmed the prenatal diagnosis. In this case, fetal MRI provided
      excellent spatial and tissue resolution with multiplanar display. It revealed
      additional diagnostic information and improved imaging conspicuity. MRI
      complemented sonography for further differentiating clinical and sonographic
      findings.

PMID- 12504325
TI  - Primary non-odontogenic tumors of the jawbones: an overview of essential
      radiographic findings.
AB  - The jawbones, namely the maxilla and mandible, can be the sites of a multitude of
      neoplastic conditions. Given the variety of processes affecting this particular
      anatomic area, formulation of a precise diagnosis often can be challenging to the
      radiologist and the clinician, who may not be familiar with the imaging findings
      fundamental to diagnosis. Although advanced imaging methods have been developed,
      routine radiography remains the mainstay in the initial assessment of osseous
      lesions involving the jawbones. We review and summarize the imaging appearances
      of non-odontogenic tumors of the jawbones and illustrate example cases of these
      uncommon neoplasms of bone. Detailed patient history, physical examination,
      laboratory evaluation and histopathologic analysis are of paramount importance in
      diagnostic approach and, in most cases, are to be considered in the imaging
      evaluation of a given lesion. Correct interpretation of the imaging features of
      lesions involving the jawbones suggests the diagnosis, aids in presurgical
      planning and improves patient management.

PMID- 12504328
TI  - Precise peptide sequencing and protein quantification in the human proteome
      through in vivo lysine-specific mass tagging.
AB  - Proteomics studies demand new scalable and automatable MS-based methods with
      higher specificity and accuracy. Here we describe an accurate and efficient
      method for both precise quantification and comprehensive de novo identification
      of peptide sequences in complex mixtures. The unique feature of this method is
      based on the incorporation of deuterium-labeled (heavy) lysines into proteins
      through in vivo cell culturing, which introduces specific mass tags at the
      carboxyl termini of proteolytic peptides when cleaved by certain proteases. The
      mass shift between the unlabeled and the deuterated lysine (lys-d4) assigns a
      mass signature to all lysine-containing peptides in any pool of proteolytic
      peptides. Lys-d4 tags can also serve as internal markers in MS/MS fragment
      spectra when they are buried in some peptide sequences due to miscleavages. This
      signal specificity circumvents the mass accuracy limitations in determining
      particular amino acid residues for de novo sequencing. Further, this strategy of
      lysine-specific tagging was successfully implemented to measure the differential
      protein expression of human skin fibroblast cells in response to heat shock.

PMID- 12504329
TI  - Characterization of the allosteric inhibition of a protein-protein interaction by
      mass spectrometry.
AB  - The allosteric inhibition of the lymphocyte function associated antigen
      1/intercellullar adhesion molecule (LFA-1/ICAM-1) interaction, by a class of
      small molecules, is characterized by a battery of mass spectrometric techniques.
      Binding of hydantoins to the I domain of LFA-1 is observed by size exclusion
      chromatography/mass spectrometry (SEC/MS) and by direct electrospray ionization
      mass spectrometry (ESI/MS). A photoactive hydantoin analog specifically labels an
      amino acid residue of LFA-1 I domain. Competition with this photoaffinity
      labeling by a panel of inhibitors is correlated with their Kd's for inhibition of
      the LFA-1/ICAM interaction. Alterations to the tertiary structure of LFA-1 I
      domain, upon compound binding, are inferred from perturbation in the ESI mass
      spectrum of the polypeptide's charge state distribution and by an altered level
      of nonspecific multimer formation. The results demonstrate specific,
      stoichiometric, reversible binding of the hydantoins to LFA-1. They further show
      correlation of this binding with activity and indicate alterations in the
      polypeptide's tertiary structure, on hydantoin binding, consistent with the
      proposed mechanism for inhibition of the protein-protein interaction.

PMID- 12504330
TI  - Evaluation of an improved general unknown screening procedure using liquid
      chromatography-electrospray-mass spectrometry by comparison with gas
      chromatography and high-performance liquid-chromatography--diode array detection.
AB  - This paper presents an improved, comprehensive liquid chromatography-electrospray
      mass spectrometry (LC-ES-MS) general unknown screening (GUS) procedure for drugs
      and toxic compounds and its comparison with conventional techniques in routine
      laboratory conditions. Chromatographic separation involved an X-TERRA MS C18, 3.5
      microm (100 mm x 1 mm i.d.) column together with a 25-min long gradient of
      acetonitrile in pH 3, 2 mM ammonium formate delivered at a 50 microl/min flow
      rate. Two different in-source collision-induced dissociation voltages were
      alternated, both in the positive and in the negative ion modes. Reconstructed
      spectra were then obtained in both polarities by adding up spectra obtained with
      low and high energy, resulting in spectra presenting a sufficient number of
      specific fragment ions for unambiguous and fast identification of compounds. Two
      large mass spectral libraries of drugs and toxic compounds were built and an
      efficient automated signal processing, library searching and report editing
      algorithm developed. Using a common, efficient solid-phase extraction procedure,
      this LC-ES-MS technique was compared to GC-MS and HPLC-DAD GUS procedures for the
      identification of a priori unknown compounds in 51 serum samples consecutively
      sent to the laboratory for GUS. The present LC-MS method identified 75% of the
      compounds contained in these samples (versus 66% for GC-MS and 71% for HPLC-DAD),
      including 8% that the other two techniques failed to identify (versus 8% for GC
      MS and 9.5% for HPLC-DAD). Therefore, it is complementary to GC-MS and/or HPLC
      DAD and helps enlarge the range of drugs detected in clinical toxicology. It
      could be useful as well in forensic toxicology to confirm a positive result, as
      38% of all the compounds were detected by the three techniques and 36% by two of
      them.

PMID- 12504332
TI  - Reduction of Cu(II) in matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - The mechanisms of the reduction of Cu(II) in matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI) are studied. In MALDI mass
      spectra, ions cationized by copper mostly contain Cu(I) even if Cu(II) salts are
      added to the sample. It was found that Cu(II) was reduced to Cu(I) by gas-phase
      charge exchange with matrix molecules, which is a thermodynamically favorable
      process. Under some conditions, large amounts of free electrons are present in
      the plume. Cu(II) can be even more efficiently reduced to Cu(I) by free electron
      capture in the gas phase. The matrices studied in this work are nicotinic acid,
      dithranol, and 2,5-dihydroxybenzoic acid.

PMID- 12504331
TI  - Electron capture dissociation and infrared multiphoton dissociation of
      oligodeoxynucleotide dications.
AB  - We report electron capture dissociation (ECD) and infrared multiphoton
      dissociation (IRMPD) of doubly protonated and protonated/alkali metal ionized
      oligodeoxynucleotides. Mass spectra following ECD of the homodeoxynucleotides
      polydC, polydG, and polydA contain w or d "sequence" ions. For polydC and polydA,
      the observed fragments are even-electron ions, whereas radical w/d ions are
      observed for polydG. Base loss is seen for polydG and polydA but is a minor
      fragmentation pathway in ECD of polydC. We also observe fragment ions
      corresponding to w/d plus water in the spectra of polydC and d(GCATGC). Although
      the structure of these ions is not clear, they are suggested to proceed through a
      pentavalent phosphorane intermediate. The major fragment in ECD of d(GCATGC) is a
      d ion. Radical a- or z-type fragment ions are observed in most cases. IRMPD
      primarily results in base loss, but backbone fragmentation is also observed.
      IRMPD provides more sequence information than ECD, but the spectra are more
      complex due to extensive base and water losses. It is proposed that the smaller
      degree of sequence coverage in ECD, with fragmentation mostly occurring close to
      the ends of the molecules, is a consequence of a mechanism in which the electron
      is captured at a P=O bond, resulting in a negatively charged phosphate group.
      Consequently, at least two protons (or alkali metal cations) must be present to
      observe a w or d fragment ion, a requirement that is less likely for small
      fragments.

PMID- 12504333
TI  - Molecular mass determination of saturated hydrocarbons: reactivity of eta5
      cyclopentadienylcobalt ion (CpCo*+) and linear alkanes up to C-30.
AB  - The present study demonstrates the feasibility of the eta5-cyclopentadienylcobalt
      ion (CpCo*+) as a suitable cationization reagent for saturated hydrocarbon
      analysis by mass spectrometry. Ion/molecule reactions of CpCo*+ and three medium
      chain-length n-alkanes were examined using Fourier-transform ion cyclotron
      resonance mass spectrometry. Second-order rate constants and reaction
      efficiencies were determined for the reactions studied. Loss of two hydrogen
      molecules from the CpCo-alkane ion complex was found to dominate all reactions (
      > or = 80%). Furthermore, this dehydrogenation reaction efficiency increases with
      increasing chain length. These preliminary results suggest that the CpCo*+ ion
      may be a promising cationization reagent of longer chain saturated hydrocarbons
      and polyolefins.

PMID- 12504334
TI  - GC/MS determination of fatty acid picolinyl esters by direct curie-point
      pyrolysis of whole bacterial cells.
AB  - A single-step method suitable for cellular fatty acid derivatization to picolinyl
      esters with the use of a pyrolyzer as a thermochemical micro-reactor was
      developed for whole bacterial cells. This reduced the preparation time from
      several hours to less than two minutes. In addition, the minimal bacterial mass
      required for analysis was reduced from several milligrams to micrograms. The
      profiling of cellular fatty acids of gram-positive and gram-negative bacteria was
      achieved using three derivatization methods: preparation of methyl esters, beta
      picolinyl esters by Harvey's method and a new method based on pyrolytic
      derivatization to beta-picolinyl esters. It was shown that there are great
      similarities between profiles of bacterial fatty acids determined by the
      pyrolytic derivatization method and traditional preparation methods of picolinyl
      and methyl esters prior to GC analysis. Results obtained by application of the
      new technique have immense diagnostic value due to vast similarities between
      profiles of fatty acids derivatized to either picolinyl and methyl esters.
      Although the latter are referred to in the literature most often, mass spectra of
      picolinyl esters contain fragment ions that provide structural information about
      the chain branching, position of unsaturation, and other substituents.

PMID- 12504335
TI  - Incremented alkyl derivatives enhance collision induced glycosidic bond cleavage
      in mass spectrometry of disaccharides.
AB  - Electrospray ionization and collision induced dissociation on a triple quadrupole
      mass spectrometer were used to determine the effect of spatial crowding of
      incremented alkyl groups of two anomeric pairs of peralkylated (methyl to pentyl)
      disaccharides (maltose/cellobiose and isomaltose/gentiobiose). Protonated
      molecules were generated which underwent extensive fragmentation under low energy
      conditions. For both the 1 --> 4 and 1 --> 6 alpha and beta isomers, at
      comparable collision energies the methyl derivative exhibited the least
      fragmentation followed by ethyl, propyl, butyl, and pentyl. Collision energy is
      converted to rotational-vibrational modes in competition with bond cleavage, as
      represented by the slope of product/parent ion (D/P) ratio versus offset energy.
      Variable rotational freedom at the glycosidic linkage with incremented alkyl
      groups is hypothesized to be responsible for this effect. Discrimination of
      anomeric configuration was also assessed for these stereoiosmeric disaccharides.
      A systematic study showed that an increasing discrimination was attained for the
      1 --> 4 isomeric pair as the size of the derivative increased from methyl to
      pentyl. No anomeric discrimination was attained for the 1 --> 6 isomeric pair.
      Parent and product ion scans confirmed the consistency of fragmentation pathways
      among derivatives. Chem-X and MM3 molecular modeling programs were used to obtain
      minimum energy structures and freedom of motion volumes for the permethylated
      disaccharides. The modeling results correlated with the fragmentation ratios
      obtained in the mass spectrometer giving strong indication that the collision
      induced spectra are dependent on the freedom of rotational motion around the
      glycosidic bond.

PMID- 12504338
TI  - Inhalation toxicity of dimethyl piperidinone.
AB  - A mixture of 1,3-dimethyl-2-piperidinone and 1,5-dimethyl-2-piperidinone (DMPD)
      (approximately 63-37 parts by weight) was tested for its inhalation toxicity in
      rats following 90-day repeated exposures. Male and female rats were exposed whole
      body to either 0, 51, 230, or 310 mg/m(3) DMPD for 6 h/day, 5 days/weak for 90
      days. Clinical signs, growth, clinical pathology, tissue pathology,
      neurobehavior, neuropathology, and semen quality were evaluated. No compound
      related adverse effects were noted in clinical signs, body weights, food
      consumption, clinical laboratory evaluations, neurobehavioral evaluations,
      neuropathology, or sperm counts. Laryngeal changes consisting of minimal squamous
      epithelial hyperplasia and degeneration/necrosis of the cartilage were present in
      male and female rats exposed to 310 mg/m(3) both immediately following exposure
      and after the 1-month recovery period Male rats exposed to DMPD had increased
      relative kidney weights, increased formation of hyaline droplets and granular
      casts, and increased incidence of chronic progressive nephropathy. These kidney
      effects are consistent with increased accumulation of the urinary protein alpha(2
      mu)-globulin, which has been well essential for several xenobiotics. The
      subsequent increased incidence of progressive nephropathy was specific to male
      rats with the alpha(2 mu) syndrome. Male and female rats exposed to 230 or 310
      mg/m(3) had centrilobular hepatocellular hypertrophy, and male rats exposed to
      310 mg/m(3) had increased relative liver weights. These liver changes were
      reversible following the recovery period and were considered not to represent
      adverse toxicological effects of treatment. Since the male rat-specific renal
      findings do not connote adversity for man and are net considered relevant to
      human hazard assessment, the no-observed-effect level in male and female rats was
      230 mg/m(3), based on the microscopic changes in the larynx exposed to 310
      mg/m(3).

PMID- 12504339
TI  - Pyridostigmine bromide modulates topical irritant-induced cytokine release from
      human epidermal keratinocytes and isolated perfused porcine skin.
AB  - Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic
      treatment against organophosphate nerve agent exposure, and were exposed to the
      insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET).
      The purpose of this study was to assess the effects of PB to modulate release of
      inflammatory biomarkers after topical chemical exposure to chemical mixtures
      containing permethrin and DEET applied in ethanol or water vehicles. Treatments
      were topically applied to isolated perfused porcine skin flaps (IPPSFs).
      Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha)
      and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential
      inflammatory effects after complex mixture application. IPPSFs (n=4/treatment)
      were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in
      ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB.
      Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate
      low level organophosphate nerve agent exposure. Timed IPPSF venous effluent
      samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by
      EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2)
      release. Effects on TNF-alpha were vehicle dependent. To probe the potential
      mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were
      exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was
      assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol
      treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these
      studies suggest that systemic exposure to PB suppressed IL-8 release at multiple
      time points in two skin model systems. This interaction merits further study.

PMID- 12504340
TI  - Investigations into the potential neurotoxicity induced by diselenides in mice
      and rats.
AB  - It is well known that selenium is highly toxic to several species of mammals.
      Here we report the potential neurotoxicity of diselenides, as measured by the
      manifestation of seizures. The modulation of various neurotransmitter systems
      potentially involved in seizure episodes and death was also evaluated. The
      results of the present investigation suggest that toxicity of diselenides depends
      on the route of administration as well the species (rats or mice). These data
      show that modulation of more than one neuronal system can account for diselenide
      induced seizures in mice. Additionally, changes in structure of diselenides, such
      as to introduce a functional group, influence the appearance of seizure episode.
      Conversely, all allosteric modulators tested did not protect dipropyl diselenide
      induced seizures, indicating that aliphatic is more toxic than aromatic
      diselenides. Acute treatment with dipropyl diselenide inhibited [3H]-glutamate
      uptake to the crude synaptosomes. In contrast animals injected with diphenyl
      diselenide did not inhibit [3H]-glutamate uptake.

PMID- 12504341
TI  - Identification of an abnormal beryllium lymphocyte proliferation test.
AB  - The potential hazards from exposure to beryllium or beryllium compounds in the
      workplace were first reported in the 1930s. The tritiated thymidine beryllium
      lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely
      used to screen beryllium exposed workers in the nuclear industry for sensitivity
      to beryllium. The clinical significance of the BeLPT was described and a standard
      protocol was developed in the late 1980s. Cell proliferation is measured by the
      incorporation of tritiated thymidine into dividing cells on two culture dates and
      using three concentrations of beryllium sulfate. Results are expressed as a
      'stimulation index' (SI) which is the ratio of the amount of tritiated thymidine
      (measured by beta counts) in the simulated cells divided by the counts for the
      unstimulated cells on the same culture day. Several statistical methods for use
      in the routine analysis of the BeLPT were proposed in the early 1990s. The least
      absolute values (LAV) method was recommended for routine analysis of the BeLPT.
      This report further evaluates the LAV method using new data, and proposes a new
      method for identification of an abnormal or borderline test. This new statistical
      biological positive (SBP) method reflects the clinical judgment that: (i) at
      least two SIs show a 'positive' response to beryllium; and (ii) that the maximum
      of the six SIs must exceed a cut-point that is determined from a reference data
      set of normal individuals whose blood has been tested by the same method in the
      same serum. The new data is from the Y-12 National Security Complex in Oak Ridge
      (Y-12) and consists of 1080 workers and 33 non-exposed control BeLPTs (all tested
      in the same serum). Graphical results are presented to explain the statistical
      method, and the new SBP method is applied to the Y-12 group. The true positive
      rate and specificity of the new method were estimated to be 86% and 97%,
      respectively. An electronic notebook that is accessible via the Internet was used
      in this work and contains background information and details not included in the
      paper.

PMID- 12504342
TI  - Cadmium-induced decrement of the LH receptor expression and cAMP levels in the
      testis of rats.
AB  - Cadmium (Cd) is a widespread environmental pollutant, characterized by its
      ability to affect various organs. Adverse effect of Cd on the testis including
      decreased testosterone production are well-known phenomena, but the cellular
      events explaining these effects have not yet been established. In the present
      study the initial steps of gonadotropin mediated testosterone biosynthesis were
      examined in vivo in rats, in relation to Cd dose and time after injection. In the
      dose-response experiment Male Sprague-Dawley rats received a single subcutaneous
      (s.c.) injection of CdCl(2) (1, 5 or 10 micromol/kg body weight) and were
      sacrificed 48 h after injection. A statistically significant decrease in
      luteinizing hormone (LH) receptor mRNA level in the testicular tissue was
      demonstrated at the highest dose (10 micromol/kg). In the temporal-response
      experiment rats were given 10 micromol/kg of CdCl(2) s.c. and sacrificed 0.48,
      4.8, 48 or 144 h after injection. LH receptor mRNA levels as well as cyclic
      adenosine monophosphate (cAMP) levels were found to be significantly lowered at
      48 and 144 h. These observations of the mechanisms whereby Cd exerts its effect
      on the initial steps of testosterone biosynthesis are the first from in vivo
      experiments.

PMID- 12504343
TI  - Comparative study of the toxic effects of fumonisin B1 in rat C6 glioma cells and
      p53-null mouse embryo fibroblasts.
AB  - The present experiments have been carried out in order to study (comparatively)
      oxidative stress and its consequences (i.e. modifications of DNA bases and/or DNA
      fragmentation), cell cycle progression (through two generations) and apoptosis in
      C6 glioma cells (with normal p53 status) and p53-null mouse embryonic fibroblasts
      (MEF) after incubation with fumonisin B(1) (FB(1)). Further endpoints, including
      protein and DNA syntheses as well as cytotoxicity, have been also studied. The
      results show that FB(1) (incubation) produced a significant increase of
      malondialdehyde (MDA) production (suggestive of lipid peroxidation) which was
      prevented by antioxidant agents in both cell types. Moreover, FB(1) induced a
      significant and dose-related increase of 8-OH-dG and DNA fragmentation in both C6
      glioma and MEF cells. Unlike MEF cells, apoptotic C6 glioma cells were observed
      after FB(1) incubation. Moreover, suppression of cell cycle progression was
      observed in C6 glioma but not in MEF cell incubated with FB(1). The results
      suggest a possible loss of protective mechanisms (such as p53-dependent apoptosis
      and cell cycle arrest) in FB(1)-damaged MEF cells and confirm that cells lacking
      of mechanisms governed by p53 gene would be more susceptible to neoplastic
      cascade or mutation following DNA lesions induced by this mycotoxin.

PMID- 12504344
TI  - Dose-dependent biotransformation of arsenite in rats--not S-adenosylmethionine
      depletion impairs arsenic methylation at high dose.
AB  - Arsenite (AsIII) is eliminated via excretion and methylation. Monomethylarsonous
      acid (MMAsIII) is a super toxic metabolite of AsIII, while dimethylarsinic acid
      produced in the next metabolic step is relatively atoxic. Since the role of
      methylation in the acute toxicity and elimination of AsIII in vivo is unclear, we
      have examined the excretion and tissue retention of AsIII and its metabolites in
      rats exposed to increasing AsIII doses. Rats were injected i.v. with 20, 50 and
      125 micromol/kg AsIII and arsenic metabolites in bile, urine and tissues were
      analysed. The excretion of AsIII increased almost proportionately to the dose,
      while its concentration in tissues rose more than proportionately. In contrast,
      the excretion and tissue concentrations of methylated metabolites increased less
      than the dosage, or they even decreased after injection of the largest dose of
      AsIII. To elucidate the mechanism of the dose-dependent decrease of methylation,
      we quantified S-adenosylmethionine (SAME), glutathione (GSH), and adenine
      nucleotides in the liver of AsIII-injected rats. AsIII decreased the hepatic
      concentrations of GSH and adenosine 5'-triphosphate (ATP) and the energy charge
      in a dose-dependent manner, but increased the level of SAME. Thus, impaired
      methylation after AsIII overdose is not due to SAME shortage, but probably to
      methyltransferase inhibition. It appears that exhausted elimination capacity of
      AsIII, rather than MMAsIII produced from AsIII, contributes significantly to the
      acute toxicity of AsIII. After GSH depletion the retained AsIII can increasingly
      inhibit SH-enzymes, thus causing ATP depletion and energetic disorder.

PMID- 12504345
TI  - Immature rat uterotrophic assay of 18 chemicals and Hershberger assay of 30
      chemicals.
AB  - We performed an immature rat uterotrophic assay of 18 chemicals and Hershberger
      assay of 30 chemicals to assess the relationship between the results of two
      assays. The chemicals tested by the uterotopic assay were 4-n-amylphenol, p
      dodecyl-phenol, p-(tert-pentyl)phenol, 4-cyclohexylphenol, 4-(1-adamantyl)phenol,
      4,4'-thiobis-phenol, diphenyl-p-phenylenediamine, 4-hydroxyazobenzene, 4
      (phenylmethyl)phenol, 4,4'-(hexafluoroisopropylidene)diphenol, 2,2-bis(4
      hydroxyphenyl)-4-methyl-n-pentane, 4,4'-(octahydro-4,7-methano-5H-inden-5
      ylidene)bisphenol, 4,4'-dihydroxybenzophenone, 2,2',4,4'
      tetrahydroxybenzophenone, 4-hydroxybenzophenone, 2,4,4'-trihydroxybenzophenone,
      testosterone enanthate, and methyltestosterone. The chemicals tested by the
      Hershberger assay were the 18 chemicals tested in the uterotrophic assay plus the
      following: 17 alpha estradiol, estrone, equilin, norethindrone, norgestrel,
      ethynyl estradiol, bisphenol A, bisphenol B, bisphenol F, 4-tert-octylphenol, p
      cumyl phenol, and nonylphenol. All chemicals examined in this study were positive
      in a reporter gene assay for ER-alpha. In the immature rat uterotrophic assay,
      all chemicals induced uterotrophy and p-(tert-pentyl)phenol, 4,4'-thiobis-phenol,
      4-(phenylmethyl)phenol, 4,4'-(hexafluoroisopropylidene)diphenol, 2,2-bis(4
      hydroxyphenyl)-4-methyl-n-pentane, 4,4'-(octahydro-4,7-methano-5H-inden-5
      ylidene)bisphenol, 4,4'-dihydroxybenzophenone, 2,2',4,4'
      tetrahydroxybenzophenone, 4-hydroxybenzophenone, and 2,4,4'
      trihydroxybenzophenone exerted both estrogen agonistic effect and reduced the
      estrogenic effect of ethynylestradiol. In the Hershberger assay, a clear androgen
      agonistic effect was detected in the androgen derivatives testosterone enanthate
      and methyltestosterone.

PMID- 12504346
TI  - Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats.
AB  - Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound
      found at low (part-per-billion) concentrations in serum and liver samples from
      humans and fish-eating wildlife. This study investigated the hypotheses that
      early hepatocellular peroxisomal proliferation and hepatic cellular proliferation
      are factors in chronic liver response to dietary dosing, that lowering of serum
      total cholesterol is an early clinical measure of response to treatment, and that
      liver and serum PFOS concentrations are proportional to dose and cumulative dose
      after sub-chronic treatment. PFOS was administered in diet as the potassium salt
      at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4
      or 14 weeks. At 4 weeks, effects included decreased serum glucose and an
      equivocal (<twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity
      in 20 ppm dose-group males in one of two assay systems [corrected]. At 14 weeks,
      the 20 ppm males had increased liver weight, decreased serum cholesterol,
      increased non-segmented neutrophils, and increased ALT. Relative liver weights
      and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic
      hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and
      the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not
      observed at 14 weeks, and the average hepatocyte proliferation index was not
      increased, although, individual animals had mild increases. Serum and liver PFOS
      concentrations were proportional to dose and cumulative dose. Serum
      concentrations were generally higher in females than in males. The liver-to-serum
      PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no
      observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL
      corresponded to mean serum PFOS concentrations of 44 ppm (microg/ml) in males and
      64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370
      ppm in females. Results for this study: (1) did not provide strong evidence for
      hepatocellular peroxisomal or cellular proliferation at the doses tested; (2)
      suggested that lowering of serum total cholesterol may not be the earliest
      clinically-measurable response to treatment in the rat; and (3) confirmed that
      serum and liver PFOS concentrations on repeated dosing are proportional to dose
      and cumulative dose.

PMID- 12504347
TI  - The antioxidative and antihistaminic properties of quercetin in ethanol-induced
      gastric lesions.
AB  - The role of reactive oxygen species in the pathogenesis of acute ethanol-induced
      gastric mucosal lesions and the effects of quercetin were evaluated in an
      experimental model. In addition, the effects of quercetin on gastric damage were
      evaluated histopathologically. Rats were divided into three groups as control
      rats, ethanol treated rats and ethanol+quercetin treated rats. Ethanol group was
      given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled
      water. Quercetin (200 mg/kg body wt.) was given by intragastric gavage 120 min
      before the administration of ethanol. Gastric tissue thiobarbituric acid reactive
      substance levels, carbonyl compounds, histamine levels and myeloperoxidase
      activities were found to be increased in ethanol treated rats and quercetin
      treatment reversed these increases. No statistically significant changes were
      found between all groups in catalase activity. The superoxide dismutase activity
      dropped significantly after ethanol treatment and quercetin treatment increased
      this enzyme activity. Gastric damage was confirmed histomorphometrically by
      significant increases in the number of mast cells and gastric erosions in ethanol
      treated rats. It was also confirmed that quercetin treatment significantly
      decreased the number of mast cells and reduced the area of gastric erosions. The
      results suggest that the gastroprotective effect of quercetin in this
      experimental model could be due to its antiperoxidative, antioxidant and
      antihistaminic effects.

PMID- 12504348
TI  - Inhibitory activity of epigallocatechin gallate (EGCg) in paraquat-induced
      microsomal lipid peroxidation--a mechanism of protective effects of EGCg against
      paraquat toxicity.
AB  - Recently we have reported that epigallocatechin gallate (EGCg), a major component
      of Japanese green tea, significantly increased the survival rate of paraquat (Pq)
      poisoned mice. This paper describes two biochemical activities of EGCg, which
      relate to its protective effects against Pq toxicity. EGCg inhibited Pq-induced
      microsomal malondialdehyde (MDA) productions in rat liver microsome system
      containing 40 microM FeSO(4). Forty micromolar EGCg inhibited MDA production
      significantly. EGCg may inhibit the Pq-induced MDA production by at least two
      mechanisms. One may be iron-chelating activity as the inhibition disappeared when
      excess amounts of FeSO(4) were added to the reaction mixture, which indicated
      that EGCg reduced iron driven lipid peroxidation by pulling out available irons
      in the reaction mixture. The other is radical scavenging activity. EGCg scavenged
      DMPO-OOH spin adducts generated by the microsome-Pq system. The dose response
      curve of EGCg was similar to that obtained by ascorbic acid which is a typical
      water-soluble radical scavenger. Although ascorbic acid had a potential activity
      of scavenging superoxide radicals, it can not be recommended to use for the
      treatment of Pq poisoning, because ascorbic acid acts as a pro-oxidant in the
      presence of free transition metal ions by accelerating the Fenton reaction
      (Fe(2+)+H(2)O(2)-->Fe(3+)+OH(-)+OH*), which is responsible for lipid
      peroxidation. On the contrary, EGCg inhibited iron-driven lipid peroxidation
      presumably not only by chelating to Fe ions but also by scavenging superoxide
      radicals, which are responsible for the reduction of ferric (Fe(3+)) to ferrous
      (Fe(2+)) that catalyzes the Fenton reaction. Chelating and radical scavenging
      activity of EGCg can be expected simultaneously in the occurrence of Pq toxicity,
      which may explain the protective effects of EGCg against Pq toxicity.

PMID- 12504349
TI  - Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour.
AB  - Large interindividual differences occur in human nicotine disposition, and it has
      been proposed that genetic polymorphisms in nicotine metabolism may be a major
      determinant of an individual's smoking behaviour. Hepatic cytochrome P4502A6
      (CYP2A6) catalyses the major route of nicotine metabolism: C-oxidation to
      cotinine, followed by hydroxylation to trans-3'-hydroxycotinine. Nicotine and
      cotinine both undergo N-oxidation and pyridine N-glucuronidation. Nicotine N-1
      oxide formation is catalysed by hepatic flavin-containing monooxygenase form 3
      (FMO3), but the enzyme(s) required for cotinine N-1'-oxide formation has not been
      identified. trans-3'-Hydroxycotinine is conjugated by O-glucuronidation. The
      uridine diphosphate-glucuronosyltransferase (UGT) enzyme(s) required for N- and O
      glucuronidation have not been identified. CYP2A6 is highly polymorphic resulting
      in functional differences in nicotine C-oxidation both in vitro and in vivo;
      however, population studies fail to consistently and conclusively demonstrate any
      associations between variant CYP2A6 alleles encoding for either reduced or
      enhanced enzyme activity with self-reported smoking behaviour. The functional
      consequences of FMO3 and UGT polymorphisms on nicotine disposition have not been
      investigated, but are unlikely to significantly affect smoking behaviour.
      Therefore, current evidence does not support the hypothesis that genetic
      polymorphisms associated with nicotine metabolism are a major determinant of an
      individual's smoking behaviour and exposure to tobacco smoke.

PMID- 12504350
TI  - Lung function and airway inflammation in rats following exposure to combustion
      products of carbon-graphite/epoxy composite material: comparison to a rodent
      model of acute lung injury.
AB  - Pulmonary function and inflammation in the lungs of rodents exposed by inhalation
      to carbon/graphite/epoxy advanced composite material (ACM) combustion products
      were compared to that of a rodent model of acute lung injury (ALI) produced by
      pneumotoxic paraquat dichloride. This investigation was undertaken to determine
      if short-term exposure to ACM smoke induces ALI; and to determine if smoke
      related responses were similar to the pathogenic mechanisms of a model of lung
      vascular injury. We examined the time-course for mechanical lung function,
      infiltration of inflammatory cells into the lung, and the expression of three
      inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage
      inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344
      rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or
      were given i.p. injections of paraquat dichloride. Measurements were determined
      at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no
      changes in lung function indicative of ALI throughout the 7-day observation
      period, despite the acute lethality of the smoke atmosphere. However, the animals
      showed signs of pulmonary inflammation. The expression of TNF-alpha was
      significantly increased in the lavage fluid 1 day following exposure, which
      preceded the maximum leukocyte infiltration. MIP-2 levels were significantly
      increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte
      infiltration. IFN-gamma was significantly increased in the lung tissue at day 7,
      which occurred during the resolution of the inflammatory response. The paraquat,
      which was also lethal to a small percentage of the animals, caused several
      physiologic changes characteristic of ALI, including significant decreases in
      lung compliance, lung volumes/capacities, distribution of ventilation, and gas
      exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly
      in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also
      preceded the maximum neutrophil infiltration. The differences in the time-course
      and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the
      differences in the temporal relationship between their expression and
      infiltration of inflammatory cells may have accounted for the differences in lung
      function between paraquat treated and ACM smoke exposed animals.

PMID- 12504351
TI  - Jejunal transfer rates of 109cadmium chloride increase in rats in vitro and in
      vivo after oral pretreatment with cadmium or zinc chloride.
AB  - An increased body retention of Cd in rats orally pretreated with Cd or Zn is
      explained by induction of hepatic and renal metallothionein. Whether intestinal
      absorption of Cd increases after such treatments is not clear yet. To approach
      this problem we measured jejunal transfer rates of 109Cd in vitro and in vivo in
      pretreated rats (0.44 mmol Cd/l or 4.6 mmol Zn/l in the drinking water for 10
      days) and compared them with those of untreated controls. Isolated jejunal
      segments were used for in vitro perfusion. In vivo perfusion was performed in
      anaesthetized rats with blood collected from mesenteric venules substituting
      corresponding losses by reinfusion of rat blood. Water and glucose transfer did
      not differ between controls and pretreated rats. At a luminal concentration of 5
      micromol 109CdCl2/l, Cd and Zn pretreatment significantly increased the transfer
      rate of 109Cd in vitro and in vivo similarly. The 109Cd transfer rates in
      controls in the final perfusion intervals (80-120 min) were 0.06 (pmol/cm/min) in
      vivo and 0.05 in vitro; the corresponding rates in Cd or Zn pretreated rats were
      significantly higher (P<0.05) and amounted to 0.11 and 0.18 or 0.15 and 0.23,
      respectively. Mucosal concentrations of 109Cd measured at the end of the
      perfusion period tended to be lower in the pretreated animals than in the
      controls. This suggests that pretreatment with Cd or Zn reduces the amount of
      109Cd bound to the tissue leaving more 109Cd for the transfer step. As compared
      to a level of mucosal metallothionein of 8 microg/g wet weight in controls,
      increased amounts of 67 or 52 microg/g wet weight in the Cd or Zn pretreated
      rats, respectively, thus did not decrease but increased transfer rates of 109Cd.
      Therefore, increased small intestinal transfer rates of Cd can contribute to
      increase the body retention of Cd seen after oral pretreatment with Cd or Zn.

PMID- 12504352
TI  - Sensitive endpoints for evaluating cadmium-induced acute toxicity in LLC-PK1
      cells.
AB  - Cadmium chloride (CdCl(2)) is a nephrotoxicant that causes damage to the proximal
      tubular epithelium. In vivo, it increases the permeability of epithelial
      surfaces, while in vitro, it acts on active trans-epithelial ion transport. The
      purpose of this study was to investigate CdCl(2) effects on a porcine renal
      proximal tubular epithelial cell line (LLC-PK1), and, in particular, to identify
      sensitive endpoints revealing damage both at the epithelial barrier level and at
      the molecular level. After exposure of the cells to CdCl(2), trans-epithelial
      resistance (TER) decreased while paracellular permeability (PCP) increased,
      indicating a structural alteration of the junctional complex. At the molecular
      level, we observed an increase in protective proteins, such as metallothioneins
      (MTs) and heat shock proteins (HSP70), starting from 25 microM CdCl(2), together
      with alterations in cytoskeleton organization. Production of reactive oxygen
      species (ROS) was also evident, indicating cellular oxidative stress. Our data
      indicate that CdCl(2) toxicity can be detected at the barrier level and at the
      molecular level at low concentrations, at which cytotoxicity assays are unable to
      show any damage. Therefore, these endpoints should prove very useful in studying
      heavy metal-induced acute toxicity. Exposure of the cells to higher
      concentrations of CdCl(2) (50 microM) revealed the initiation of apoptosis,
      mediated by caspase-3.

PMID- 12504353
TI  - Carcinogenic potential of o-nitrotoluene and p-nitrotoluene.
AB  - The potential of o-nitrotoluene and p-nitrotoluene to cause cancer in mammalian
      species was studied in male and female F344/N rats and B6C3F1 mice. These
      chemicals are on the EPA list of high production chemicals and there is potential
      for human exposure (High Production Volume Chemical List (2000)
      http://oaspub.cpa.gov/opptintr/chemrtk/volchall.htm.). o-Nitrotoluene,
      administered in the feed for up to 2 years, caused clear evidence for cancer at
      multiple sites in rats and mice. Male rats, receiving o-nitrotoluene in the feed
      ( approximately 0, 25, 50, or 90 mg/kg per day), developed treatment-related
      mesotheliomas, subcutaneous skin neoplasms, mammary gland fibroadenomas, and
      liver neoplasms. By 2 years, mesotheliomas, skin, liver, mammary gland and liver
      tumors also occurred in 'stop-study' male rats that received o-nitrotoluene at
      125 or 315 mg/kg per day for only the first 3 months of study. These 'stop
      studies' showed that the critical events leading to tumor formation occurred
      after 3 months of dosing, and these events were irreversible and eventually led
      to cancer at multiple sites. o-Nitrotoluene given in the feed to female rats
      (approximately 0, 30, 60, or 100 mg/kg per day) and to male and female mice
      (approximately 0, 150, 320, or 700 mg/kg per day) also caused a carcinogenic
      response. In female rats, treatment-related subcutaneous skin neoplasms and
      mammary gland fibroadenomas occurred. Hemangiosarcomas and carcinomas of the
      large intestine (cecum) were seen in treated male and female mice. In contrast to
      o-nitrotoluene, p-nitrotoluene given in the feed over approximately the same
      exposure levels caused only equivocal evidence of carcinogenic activity in male
      rats (subcutaneous skin neoplasms); some evidence of carcinogenic activity in
      female rats (clitoral gland neoplasms); equivocal evidence of carcinogenic
      activity in male mice (lung neoplasms); and no evidence of carcinogenic activity
      in female mice. Differences in the o-nitrotoluene and p-nitrotoluene carcinogenic
      activity may be due to differences in the metabolism of the parent compound to
      carcinogenic metabolites.

PMID- 12504354
TI  - Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to
      fluoride.
AB  - In an attempt to elucidate the mechanism by which excessive fluoride damages the
      central nervous system, the effects of exposure of PC12 cells to different
      concentrations of fluoride for 48 h on nicotinic acetylcholine receptors (nAChRs)
      were characterized here. Significant reductions in the number of binding sites
      for both [3H]epibatidine and [125I]alpha-bungarotoxin, as well as a significant
      decrease in the B(max) value for the high-affinity of epibatidine binding site
      were observed in PC12 cells subjected to high levels of fluoride. On the protein
      level, the alpha 3 and alpha 7 subunits of nAChRs were also significantly
      decreased in the cells exposed to high concentrations of fluoride. In contrast,
      such exposure had no significant effect on the level of the beta 2 subunit. These
      findings suggest that selective decreases in the number of nAChRs may play an
      important role in the mechanism(s) by which fluoride causes dysfunction of the
      central nervous system.

PMID- 12504355
TI  - Inflammatory mediators induced by coarse (PM2.5-10) and fine (PM2.5) urban air
      particles in RAW 264.7 cells.
AB  - Increased incidence of mortality and morbidity due to cardiopulmonary
      complications has been found to associate with elevated levels of urban air
      particles with an aerodynamic diameter <10 micron, PM10 and <2.5 micron, PM2.5.
      Respirable particles reach the lower respiratory tract where they are
      phagocytized by alveolar macrophages. Depending on particle composition, exposed
      macrophages may produce inflammatory mediators. A cascade impactor sampler was
      used to collect size-fractionated urban air particles. Particulate matter from
      the city of Rome (Italy) were collected onto stainless steel plates, and
      recovered using alcohol. The murine monocytic/macrophagic RAW 264.7 cell line was
      used to compare the ability of PM2.5-10, PM2.5 and carbon black to cause cell
      injury, such as arachidonic acid (AA) release, tumour necrosis factor alpha (TNF
      alpha) and interleukin (IL)-6 production. All test particles have been used at
      the same concentrations 30 and 120 microg/ml. Treatment with PM2.5-10 and PM2.5
      induced significant AA release after 5 h of exposure at both concentrations,
      while carbon black was effective only at the higher concentration. After 5 h of
      incubation, PM2.5-10 and PM2.5 at 120 microg/ml induced 10 times the amount of
      TNF alpha than carbon black particles. The urban air particles-stimulated TNF
      alpha production decreased after 24 h of incubation while carbon black-stimulated
      TNF alpha was not. IL-6 production was induced by PM2.5 and by PM2.5-10 but not
      by carbon black. Carbon black was consistently less effective than the urban
      particles, suggesting that, the contaminants adsorbed on the particles are
      responsible for the release of inflammatory mediators.

PMID- 12504356
TI  - Coffee increases levels of urinary 8-hydroxydeoxyguanosine in rats.
AB  - We examined whether coffee or chlorogenic acid inhibits 8-hydroxydeoxyguanosine
      (8-OHdG), one of the major forms of oxidative DNA damage, in vivo and in vitro.
      Forty-eight male Wistar rats were assigned to three treatment groups: a control
      diet group (n=16; coffee-free diet), a 0.62% coffee-diet group (n=16, dose of
      coffee consumed 125 mg/day), and a 1.36% coffee-diet group (n=16, dose of coffee
      consumed 275 mg/day) and were maintained on an experimental diet for 130 days.
      The coffee-diet resulted in significantly increased excretion of urinary
      chlorogenic acid, with the 0.62 and 1.36% coffee-diets resulting in 14.00+/-0.94
      and 15.80+/-0.41 ng/mg creatinine, respectively, whereas in control rats it was
      not detected. Using monoclonal antibody to measure 8-OHdG, it was revealed that
      coffee led to a significant increase in excretion of urinary 8-OHdG on day 130
      (46.62+/-13.42 ng/mg creatinine in 0.62% coffee-diet group and 64.58+/-20.15
      ng/mg creatinine in 1.36% coffee-diet group, P<0.05 vs. control; control group
      10.89+/-2.59 ng/mg creatinine). Furthermore, to clarify the mechanism of 8-OHdG
      formation by coffee, we investigated the in vitro effect of chlorogenic acid on 8
      OHdG formation in human placental DNA. Chlorogenic acid alone did not lead to an
      increase of 8-OHdG formation, but dramatically increased it in the presence of
      cupric chloride and H(2)O(2). However, chlorogenic acid and cupric chloride
      decreased the formation of 8-OHdG in the presence of H(2)O(2). Based on these
      results, a possible mechanism of 8-OHdG formation in vivo by chlorogenic acid is
      discussed.

PMID- 12504357
TI  - Harmonic analysis of flow in open boreholes due to barometric pressure cycles.
AB  - Barometric pressure changes can induce airflow in an open borehole or well
      screened in the vadose zone, thereby ventilating the soil surrounding the
      borehole. This paper presents an analytic model of the induced airflow and
      compares the predictions of the model with experimental measurements. This model
      may be useful for the design of passive soil vapor extraction as applied to the
      remediation of soil contaminated by volatile organic compounds (VOCs). Based on
      harmonic analysis, the model predicts the time-dependent flow in agreement with
      measurements at a borehole in strata of differing permeability. The model uses no
      adjustable parameters, but proceeds from first principles based upon known or
      estimated values of soil properties as a function of depth. In an approximation,
      the calculated flow is determined by the difference between barometric pressure
      and the attenuated pressure that would propagate vertically into the vadose zone
      in the absence of an open borehole. The attenuated vertical propagation of
      pressure can be calculated by a corresponding harmonic method presented
      previously. The model reveals that the flow in the borehole is approximately
      proportional to the horizontal permeability in the formation, and depends only
      weakly on the soil porosity and borehole radius.

PMID- 12504358
TI  - Kinematic analysis of solute mass flows in rock fractures with spatially random
      parameters.
AB  - Field data of physical properties in heterogeneous crystalline bedrock, like
      porosity and fracture aperture, is associated with uncertainty that can have a
      significant impact on the analysis of solute transport in rock fractures.
      Solutions to the central temporal moments of the residence time probability
      density function (PDF) are derived in a closed form for a solute Dirac pulse. The
      solutions are based on a model that takes into account advection along the
      fracture plane, diffusion into the rock matrix and sorption kinetics in the rock
      matrix. The most relevant rock properties including fracture aperture and several
      matrix properties as well as flow velocity are assumed to be spatially random
      along transport pathways. The mass transport is first solved in a general form
      along one-dimensional pathways, but the results can be extended to multi
      dimensional flows simply by substituting the expected travel time for inert water
      parcels. Based on data obtained with rock samples taken at Aspo Hard Rock
      Laboratory in Sweden, the solutions indicate that the heterogeneity of the rock
      properties contributes to increasing significantly both the variance and the
      skewness of the residence time probability density function for a pulse
      travelling in a fracture. The Aspo data suggests that the bias introduced in the
      variance of the residence time PDF by neglecting the effect of heterogeneity of
      the rock properties on the radionuclide migration is very large for fractures
      thinner than a few tenths of a millimetre.

PMID- 12504359
TI  - Virus retention and transport through Al-oxide coated sand columns: effects of
      ionic strength and composition.
AB  - Knowledge of the factors that influence the fate and transport of viruses in
      porous media is very important for accurately determining groundwater
      vulnerability and for developing protective regulations. In this study, six
      saturated sand column experiments were performed to examine the effects of a
      positively charged Al-oxide, which was coated on sand particles, on the retention
      and transport of viruses (phiX174 and MS-2) in background solutions of different
      ionic strength and composition. We found that the Al-oxide coating on sand
      significantly removed viruses during their transport in a phosphate buffered
      saline (PBS) solution. Mass balance calculations showed that 34% of the input MS
      2 was inactivated/irreversibly sorbed on the surface of Al-oxide coated sand
      whereas 100% of phiX174 was recovered. Results from this study also indicated
      that higher ionic strength facilitated the transport of both phiX174 and MS-2
      through the Al-oxide coated sand. This was attributed to the effect of ion
      shielding, which at higher ionic strength decreased the electrostatic attraction
      between the viral particles and the sand surface and consequently decreased virus
      sorption. Strong effect of the ionic strength indicates that an outer-sphere
      complexation mechanism was responsible for the virus sorption on the Al-oxide
      coated sand. Ion composition of the background solutions was also found to be a
      significant factor in influencing virus retention and transport. Virus transport
      was enhanced in the presence of phosphate (HPO(4)(2-)) as compared to bicarbonate
      (HCO(3)(-)), and the effect of HPO(4)(2-) was more significant on MS-2 than on
      phiX174. The presence of bivalent cations (Ca(2+) and Mg(2+)) increased virus
      transport because the cations partially screened the negative charges on the
      viruses therefore decreased the electrostatic attraction between the positively
      charged sand surface and the negatively charged viruses. Mass recovery data
      indicated that bivalent cations gave rise to a certain degree of
      inactivation/irreversibly sorption of phiX174 on the surface of Al-oxide coated
      sand. On the contrary, the bivalent cations appeared to have protected MS-2 from
      inactivation/irreversibly sorption. This study provides some insights into the
      mechanisms responsible for virus retention and transport in porous media.

PMID- 12504360
TI  - Stable hydrogen, carbon and chlorine isotope measurements of selected chlorinated
      organic solvents.
AB  - Stable hydrogen isotopes of two chlorinated solvents, trichloroethylene (TCE) and
      1,1,1-trichloroethane (TCA), provided by five different manufacturers, were
      determined and compared to their carbon and chlorine isotopic signatures. The
      isotope ratio for delta2H of different TCEs ranged between +466.9 per thousand
      and +681.9 per thousand, for delta13C between -31.57 per thousand and -27.37 per
      thousand, and for delta37Cl between -3.19 per thousand and +3.90 per thousand. In
      the case of the TCAs, the isotope ratio for delta2H ranged between -23.1 per
      thousand and +15.1 per thousand, for delta13C between -27.39 per thousand and 
      25.84 per thousand, and for delta37Cl between -3.54 per thousand and +1.39 per
      thousand. As well, a column experiment was carried out to dechlorinate
      tetrachloroethylene (PCE) to TCE using iron. The dechlorination products have
      completely different hydrogen isotope ratios than the manufactured TCEs. Compared
      to the positive values of delta2H in manufactured TCEs (between +466.9 per
      thousand and +681.9 per thousand), the dechlorinated products had a very depleted
      delta2H (less than -300 per thousand). This finding has strong implications for
      distinguishing dechlorination products (PCE to TCE) from manufactured TCE. In
      addition, the results of this study show the potential of combining 2H/1H
      analyses with 13C/12C and 37Cl/35Cl for isotopic fingerprinting applications in
      organic contaminant hydrogeology.

PMID- 12504361
TI  - Laboratory evidence of MTBE biodegradation in Borden aquifer material.
AB  - Mainly due to intrinsic biodegradation, monitored natural attenuation can be an
      effective and inexpensive remediation strategy at petroleum release sites.
      However, gasoline additives such as methyl tert-butyl ether (MTBE) can jeopardize
      this strategy because these compounds often degrade, if at all, at a slower rate
      than the collectively benzene, toluene, ethylbenzene and the xylene (BTEX)
      compounds. Investigation of whether a compound degrades under certain conditions,
      and at what rate, is therefore important to the assessment of the intrinsic
      remediation potential of aquifers. A natural gradient experiment with dissolved
      MTBE-containing gasoline in the shallow, aerobic sand aquifer at Canadian Forces
      Base (CFB) Borden (Ontario, Canada) from 1988 to 1996 suggested that
      biodegradation was the main cause of attenuation for MTBE within the aquifer.
      This laboratory study demonstrates biologically catalyzed MTBE degradation in
      Borden aquifer-like environments, and so supports the idea that attenuation due
      to biodegradation may have occurred in the natural gradient experiment. In an
      experiment with batch microcosms of aquifer material, three of the microcosms
      ultimately degraded MTBE to below detection, although this required more than 189
      days (or >300 days in one case). Failure to detect the daughter product tert
      butyl alcohol (TBA) in the field and the batch experiments could be because TBA
      was more readily degradable than MTBE under Borden conditions.

PMID- 12504362
TI  - Preliminary 3-D site-scale studies of radioactive colloid transport in the
      unsaturated zone at Yucca Mountain, Nevada.
AB  - The U.S. Department of Energy (DOE) is actively investigating the technical
      feasibility of permanent disposal of high-level nuclear waste in a repository to
      be situated in the unsaturated zone (UZ) at Yucca Mountain (YM), Nevada. In this
      study we investigate, by means of numerical simulation, the transport of
      radioactive colloids under ambient conditions from the potential repository
      horizon to the water table. The site hydrology and the effects of the spatial
      distribution of hydraulic and transport properties in the Yucca Mountain
      subsurface are considered. The study of migration and retardation of colloids
      accounts for the complex processes in the unsaturated zone of Yucca Mountain, and
      includes advection, diffusion, hydrodynamic dispersion, kinetic colloid
      filtration, colloid straining, and radioactive decay. The results of the study
      indicate that the most important factors affecting colloid transport are the
      subsurface geology and site hydrology, i.e., the presence of faults (they
      dominate and control transport), fractures (the main migration pathways), and the
      relative distribution of zeolitic and vitric tuffs. The transport of colloids is
      strongly influenced by their size (as it affects diffusion into the matrix,
      straining at hydrogeologic unit interfaces, and transport velocity) and by the
      parameters of the kinetic-filtration model used for the simulations. Arrival
      times at the water table decrease with an increasing colloid size because of
      smaller diffusion, increased straining, and higher transport velocities. The
      importance of diffusion as a retardation mechanism increases with a decreasing
      colloid size, but appears to be minimal in large colloids.

PMID- 12504363
TI  - Modelling biodegradation of hydrocarbons in aquifers: when is the use of the
      instantaneous reaction approximation justified?
AB  - In-situ bio-remediation is a viable cleanup alternative for aquifers contaminated
      by hydrocarbons such as BTEX. Transport models of varying complexity and
      capabilities are used to quantify their degradation. A model that has gained wide
      acceptance in applications is BIOPLUME II, which assumes that oxygen-limited
      biodegradation takes place as an instantaneous reaction. In this work we have
      employed theoretical analysis, using non-dimensional variables, and numerical
      modelling to establish a quantitative criterion demarcating the range of validity
      of the instantaneous reaction approximation against biodegradation kinetics.
      Oxygen was the limiting species and sorption was ignored. This criterion relates
      <Da>(o), the Dahmkohler number at oxygen depletion, to O(o)*, the ratio of
      initial to input oxygen concentration, <Da>(o) > or = 0.7(O(o)*)(2) + 0.1O(o)* +
      1.8. The derived <Da>(o) reflects the intrinsic characteristics of the physical
      transport and of the biochemical reaction, including the effect of biomass
      density. Relative availability of oxygen and hydrocarbons exerts a small
      influence on results. Theory, verified and refined via numerical simulations,
      showed that significant deviations of instantaneous reactions from kinetics are
      to be expected in the space-time region s<L(d), t<T(d) ('near source' and
      'initial period'). Under the assumptions considered, numerical simulations also
      verified the wide applicability of the computationally efficient, stoichiometry
      based (algebraic) BIOPLUME concept. Kinetic modelling is required only in active
      (engineered) bio-remediation cases, with high velocities (e.g., near pumped
      wells), and for short distances from the source.

PMID- 12504364
TI  - Dissolved organic matter effects on the performance of a barrier to polycyclic
      aromatic hydrocarbon transport by groundwater.
AB  - In order to contain the movement of organic contaminants in groundwater, a
      subsurface sorption barrier consisting of sand or clay minerals coated with a
      cationic surfactant has been proposed. The effectiveness of such a sorption
      barrier might be affected by the presence of dissolved organic matter (DOM) in
      the groundwater. To study the impact of DOM on barrier performance, a series of
      batch experiments were performed by measuring naphthalene and phenanthrene
      sorption onto sand coated with cetylpyridinium chloride (CPC) and bentonite
      coated with hexadecyltrimethylammonium bromide (HDTMA) in the presence of various
      concentrations of DOM. The overall soil-water distribution coefficient (K*) of
      naphthalene and phenanthrene onto CPC-coated sand decreased with increasing DOM
      concentration, whereas the K* of the compounds onto HDTMA-coated bentonite
      slightly increased with increasing DOM concentration. To describe the overall
      distribution of polycyclic aromatic hydrocarbons (PAHs) in the systems, a
      competitive multiphase sorption (CMS) model was developed and compared with an
      overall mechanistic sorption (OMS) model. The modeling studies showed that while
      the OMS model did not explain the CPC-coated sand experimental results, a model
      that included competitive sorption between DOM and PAH did. The experimental
      results and the modeling study indicated that there was no apparent competition
      between DOM and PAH in the HDTMA-coated bentonite system, and indicated that in
      groundwater systems with high DOM, a barrier using HDTMA-coated bentonite might
      be more effective.

PMID- 12504365
TI  - [Nucleosome-specific antibodies in systemic lupus erythematosus].

PMID- 12504366
TI  - [Relevance of anti-nucleosome antibodies detected by enzyme-based immunoassays in
      lupus diagnosis. Comparative analysis of four commercial kits].
AB  - Among the biological assays used for the diagnosis of systemic lupus
      erythematosus (SLE), the detection of anti-double strand DNA antibodies (dsDNA
      Ab) is regarded as highly specific. However this biological parameter is negative
      among 20 to 40% of patients. Recent studies have revealed potential interest of
      the anti-nucleosome antibodies in the diagnosis of the lupus, in particular when
      any anti-dsDNA antibody activity could be detected. We selected 80 sera in order
      to evaluate four commercial anti-nucleosome enzyme-based immunoassays (EIA) kits.
      Their sensitivity and specificity values were compared with those obtained by the
      detection of anti-dsDNA Ab, carried out with both a Farr assay and two EIA kits.
      No anti-nucleosome EIA kits reached performances of the Farr assay for the
      diagnosis of lupus. On the other hand, our results show an higher diagnostic
      value for some anti-nucleosome EIA kits compared with 2 anti-dsDNA EIA kits.
      Apart from SLE, anti-nucleosome antibodies can be observed in others auto-immune
      diseases, in particular Sjogren's syndromes, the primary antiphospholipid
      syndrome, the systemic sclerosis and the mixed connective tissue disease.
      Compared results of the four anti-nucleosome EIA kits highlight many
      discordances. These variations, testifying to the absence of standardization for
      this new parameter, must encourage with a careful interpretation of results,
      according to the clinical context.

PMID- 12504367
TI  - In vitro sensitivity of Mycobacterium xenopi to five antibiotics.
AB  - We tested 20 strains of Mycobacterium xenopi (M. xenopi) in order to evaluate
      their in vitro sensitivity to amikacine, clarithromycine, ethambutol, ofloxacine
      and rifampicin, by establishing minimal inhibitory concentration (MIC) on agar
      medium. MICs of amikacine, clarithromycine and ofloxacine are low, so that these
      antibiotics can be used in the treatment of M. xenopi infections. MICs of
      ethambutol are higher than seric concentrations. Though, its therapeutic use is
      due to its in vivo ability to enhance penetration of other antibiotics in
      mycobacteria. Strain sensitivity to rifampicin seems heterogeneous but the small
      number of tested strains does not entitle the exclusion of rifampicin from the
      treatment of M. xenopi infections.

PMID- 12504368
TI  - [Rhone-Alpes observatory of Streptococcus pneumoniae in 1999: 35 cases of
      meningitis].
AB  - In 1999, in Rhone-Alpes region, in a survey of resistance to antibiotics of
      Streptococcus pneumoniae, 35 cases of meningitis were observed. A retrospectic
      questionnary was sent to each participant. MICs to Penicillin, Amoxicillin and
      Cefotaxime were determined with ATB-PNEUMO gallery or E-test and by disk
      diffusion for the other antibiotics. The results were interpreted according to
      the recommendations of the CA-SFM. Mean age was 38.1 years (range : 1 month -78
      years) and sex-ratio 2/5. Eight patients had previously received antibiotics, 22
      patients had risk factors and 23 were transferred in intensive care unit. The
      patients received C3G + glycopeptide in 15 of 16 children and in 13/19 adults
      according to the consensus recommendations. Diagnostic was made on the direct
      examination of CSF in 83%, and blood cultures was positive in 74.3% of cases. The
      percentage of PRP was 48.6% with 17.1% of intermediate-amoxicilline and 14.3%
      intermediate-cefotaxime strains. Resistance to trimethoprim-sulfamethoxazole was
      45.7%, to chloramphenicol 30% and to fosfomycin 6.9%. All the strains were
      susceptible to rifampicin and vancomycin. Among the 17 PRP strains, 7 were
      belonging to serotype 6 (6 in children). The clinical outcome was fatal in 7 male
      cases (20%), without risk factors in 3 children and 6 of 7 strains were
      susceptible to penicillin. Six patients (17%) had auditive and/or neurologic
      sequellaes. This study shows that nearly 50% of strains isolated in meningitis,
      in Rhone-Alpes region, were not susceptible to penicillin, and confirms the
      frequency of sequellaes while the mortality is not related with the resistance of
      strains to the antibiotics.

PMID- 12504369
TI  - Nephroprotective effects of pentoxifylline in experimental myoglobinuric acute
      renal failure.
AB  - The nephroprotective effects of pentoxifylline, a methylxantine, were studied in
      glycerol-induced acute renal failure. Glycerol treated rats exhibited collecting
      duct and medullary ascending limb dilation and casts, with focal tubular damage,
      confined mainly to the superficial cortex. In the interstitium focal mononuclear
      infiltration was observed. In some glomeruli there was swelling of mesangial
      spaces and mesangial cells. Pentoxifylline injected to glycerol pretreated rats
      exerted a protective effect. Only few groups of proximal tubules in the
      subcapsulary region of renal cortex showed necrosis and tubulorhexis. There were
      not leukocyte infiltrations or vascular congestion. Morphometric analysis showed
      increased surface area fraction of tubular lumen in rats treated with glycerol (p
      < 0.01) compared to those in controls. Intratubular cast formations in rats
      treated with glycerol alone were significantly higher than in rats given
      pentoxifylline in addition to glycerol. Kidney cortex ectopeptidases (APA, APN
      and DPP IV) were not significantly changed after glycerol administration. Serum
      creatinine and blood urea were markedly increased in glycerol treated rats,
      however, pentoxifylline reduced significantly their levels. This study in
      glycerol-induced acute renal failure showed a marked renal morphologic and
      functional protection by pentoxifylline.

PMID- 12504370
TI  - [Epidermal growth factor: a probable oral and digestive health protector].
AB  - The integrity of oral and digestive mucosa depend on many salivary components
      like the Epidermal Growth Factor (EGF). Sometimes indicative, sometimes
      stimulated or modulated factor of oral and digestive health, EGF appears as a
      clinical marker in neoplastic and inflammatory diseases. As cellular growth
      factor, it protects the digestive mucosa with stimulation of mucus production and
      with inhibition of gastric secretion. Equally implicated in healing process, it
      enhances this one, and determines, in patients, more or less sensibility to
      inflammatory damages. Its strategic place in various pathologies, as stomach
      ulcer and tumoral process, open research prospects with a real potential of
      repair and pronostic.

PMID- 12504371
TI  - [Physiopathology and curative treatment of meningococcal diseases: current
      aspects].
AB  - Early administration of antibiotics as soon as the diagnosis of meningococcemia
      has been evoked is a significant therapeutic advance. However, the poor outcome
      of these diseases whose mortality remains high despite the current techniques of
      reanimation shows that improving the vaccination against meningococci is still of
      actuality. Diagnosing rapidly severe meningococcal disease is also a means for
      acting against the pathological activation of the inflammatory and coagulation
      pathways. Significant advances have been made in understanding the
      physiopathology of the meningococcal purpura fulminans especially about the
      deleterious role of the deficiency of the protein C and the antithrombin III. It
      is too soon to advance that the prognosis of these diseases has been improved by
      these new therapeutic approaches but the results of preliminary clinical studies
      are encouraging. However, informing parents about the first skin abnormalities
      seen in infants with purpura fulminans is essential in attempt to improve the
      efficiency of these new therapeutic strategies.

PMID- 12504375
TI  - Synthesis of a mannose heptasaccharide existing in baker's yeast, Saccharomyces
      cerevisiae X2180-1A wild-type strain.
AB  - A mannose heptasaccharide existing in baker's yeast, Saccharomyces cerevisiae
      X2180-1A wild-type strain, was effectively synthesized as its allyl glycoside via
      TMSOTf-promoted condensation of a disaccharide donor 13 with a pentasaccharide
      acceptor 12, followed by deprotection. The pentasaccharide 12 was constructed by
      coupling of 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O
      benzoyl-alpha-D-mannopyranosyl-(1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl
      (1-->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate (9) with
      allyl 6-O-acetyl-3,4-di-O-benzoyl-alpha-D-mannopyranoside (10), followed by
      deacetylation. The tetrasaccharide 9 was obtained by coupling of 2,3,4,6-tetra-O
      benzoyl-alpha-D-mannopyranosyl-(1-->3)-2,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl
      trichloroacetimidate (5) with allyl 3,4,6-tri-O-benzoyl-alpha-D-mannopyranosyl-(1
      ->2)-3,4,6-tri-O-benzoyl-alpha-D-mannopyranoside (6), followed by deallylation
      and trichloroacetimidation. The disaccharides 6 and 13 were readily obtained by
      known methods.

PMID- 12504376
TI  - Thio-sugars VII. Effect of 3-deoxy-4-S-(beta-D-gluco- and beta-D
      galactopyranosyl)-4-thiodisaccharides and their sulfoxides and sulfones on the
      viability and growth of selected murine and human tumor cell lines.
AB  - The first conversion of (1-->4)-thiodisaccharides into corresponding sulfoxides
      and sulfones by conventional oxidation with m-chloroperoxybenzoic acid (MCPBA) is
      reported. The effects of alpha-(1-->4)-3'-deoxythiodisaccharides (8-9) and their
      sulfoxide (14-15) and sulfone (16-17) derivatives on murine leukemia and human
      colon and pancreatic carcinoma cell viability were studied. Concentrations of
      thio-sugars that decreased tumor cell line viability by 50% (IC(50)), measured
      via the MTT assay, ranged from 6.4 to 38.3 microg/mL. The effect of alpha-(1-->4)
      3'-deoxythiodisaccharide derivatives were most profound on human pancreatic
      epithelial carcinoma (PANC-1) cells with compounds 8 and 9 having IC(50) values
      of 6.4 microg/mL and 8.2 microg/mL, respectively. Sulfone derivatives 16 and 17
      also had pronounced effects on PANC-1 cell viability (IC(50)=10.2 microg/mL and
      9.6 microg/mL, respectively). These results indicate that deoxythio-disaccharide
      analogs generated by functionalization of the universal chiral precursor
      levoglucosenone may have cytotoxic properties and therapeutic potential as
      anticancer agents.

PMID- 12504377
TI  - Synthesis of beta-D-GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->2)-[beta-L-Xylp-(1-->4)]
      alpha-L-Rhap-(1-->3)-alpha-L-Rhap, the repeating unit of the O-antigen produced
      by Pseudomonas solanacearum ICMP 7942.
AB  - An efficient synthesis of beta-D-GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->2)-[beta-L
      Xylp-(1-->4)]-alpha-L-Rhap-(1-->3)-alpha-L-Rhap, the repeating unit of the O
      antigen produced by Pseudomonas solanacearum ICMP 7942 and its isomer beta-D
      GlcpNAc-(1-->3)-alpha-L-Rhap-(1-->4)-[beta-L-Xylp-(1-->2)]-alpha-L-Rhap-(1-->3)
      alpha-L-Rhap was achieved via sequential assembly of the building blocks, allyl
      2,3-O-isopropylidene-alpha-L-rhamnopyranoside (2), allyl 3,4-O-isopropylidene
      alpha-L-rhamnopyranoside (3), allyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside
      (6), 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl
      trichloroacetimidate (7), and 2,3,4-tri-O-benzoyl-beta-L-xylopyranosyl
      trichloroacetimidate (12). The process was carried out in a regio- and
      stereoselective manner using glycosyl trichloroacetimidates as donors and
      unprotected or partially protected rhamnopyranosides as acceptors in the presence
      of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf).

PMID- 12504378
TI  - Synthesis of radioiodine-labeled 2-phenylethyl 1-thio-beta-D-galactopyranoside
      for imaging of LacZ gene expression.
AB  - A potent inhibitor of beta-galactosidase (EC 3.2.1.23), 2-phenylethyl 1-thio-beta
      D-galactopyranoside (PETG), was radioiodinated for noninvasive imaging of LacZ
      gene expression. In order to introduce radioiodine to the phenyl ring of PETG, 2
      (4-bromophenyl)ethanethiol was prepared and attached to the C-1 position of beta
      D-galactose pentaacetate under conditions that resulted in the exclusive
      formation of the beta anomer. The bromo group of PETG was converted to the
      tributylstannyl group where radioiododemetallation was carried out. Radioiodine
      labeled PETG tetraacetate was purified by HPLC, which can be used as a prodrug
      for biological evaluation or hydrolyzed to 2-(4-[123I/125I]iodophenyl)ethyl 1
      thio-beta-D-galactopyranoside ([123I/125I]7) under basic conditions. The
      resulting radioiodine-labeled PETG was obtained in overall 62% radiochemical
      yield (decay-corrected) and with specific activity of 46-74 GBq/micromol.

PMID- 12504379
TI  - Synthesis of neoglycoproteins containing O-methylated trisaccharides related to
      excretory/secretory antigens of Toxocara larvae.
AB  - The disaccharides allyl beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta-
      and alpha-D-galactopyranoside 10a and 10b and the trisaccharides allyl 2-O-methyl
      alpha-L-fucopyranosyl-(1-->2)-beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy
      beta- and alpha-D-galactopyranoside 18a and 18b have been prepared using stepwise
      assembly of the sugar units. The glycosidic linkages were formed employing the
      trichloroacetimidate procedure for the attachment of the galactopyranosyl residue
      and N-iodosuccinimide/triflic acid activation of an ethyl 1-thiofucopyranoside
      donor for fucosylation. Deprotection furnished the allyl glycosides which were
      converted into cysteamine-spacered ligands, activated with thiophosgene and
      subsequently linked to bovine serum albumin. The neoglycoproteins serve as
      immunoreagents to determine epitope specificities of monoclonal antibodies
      directed against highly immunogenic O-glycans located at the surface of Toxocara
      larvae.

PMID- 12504380
TI  - Synthesis of lipid A type carboxymethyl derivatives with ether chains instead of
      ester chains and their LPS-antagonistic activities.
AB  - Synthesis of lipid A type carboxymethyl derivatives having ether chains at both
      the C-3 and C-3' positions and their LPS-antagonistic activities toward human
      U937 cells are described.

PMID- 12504381
TI  - A new and efficient strategy for the synthesis of shimofuridin analogs: 2'-O-(4-O
      stearoyl-alpha-L-fucopyranosyl)thymidine and -uridine.
AB  - Two shimofuridin analogs: 2'-O-(4-O-stearoyl-alpha-L-fucopyranosyl)thymidine (2)
      and -uridine (3) have been synthesized using D-arabinose, L-fucose, thymine,
      uracil, and stearoyl chloride as the starting materials. The synthetic procedures
      involve the facile preparation of 1-(3,5-di-O-benzyl-beta-D-ribofuranosyl)thymine
      (9) and -uracil (10) by coupling of 1,2-anhydro-3,5-di-O-benzyl-alpha-D
      ribofuranose (8) with silylated thymine and uracil, and then stereoselective
      formation of the 1,2-cis (alpha) interglycoside bonds through condensation of the
      nucleoside derivatives 9 and 10 with 2-(2,3-di-O-benzyl-4-O-stearoyl-beta-L
      fucopyranosylsulfonyl) pyrimidine (18). The 1,2-anhydro-3,5-di-O-benzyl-alpha-D
      ribofuranose (8) was prepared by an improved procedure from D-arabinose.

PMID- 12504382
TI  - Structural characterisation of a perdeuteriomethylated exopolysaccharide by NMR
      spectroscopy: characterisation of the novel exopolysaccharide produced by
      Lactobacillus delbrueckii subsp. bulgaricus EU23.
AB  - The exopolysaccharide (EPS) from Lactobacillus delbrueckii subsp. bulgaricus EU23
      was perdeuteriomethylated and the perdeuteriomethylated EPS (pdm-EPS) purified by
      elution from a C(18) Sep-Pak cartridge. Both 1D and 2D NMR spectra were recorded
      for the pdm-EPS and these were interpreted to provide assignments for the
      individual 1H and 13C resonances of the sugar residues of the repeating unit.
      Using a combination of the results from monomer analysis and linkage analysis of
      the native EPS and the ROESY and HMBC NMR spectra of the pdm-EPS the following
      structure has been determined for the repeating unit:A process for characterising
      polysaccharides having low solubility in aqueous solution is reported.

PMID- 12504383
TI  - Location of O-acetyl substituents in xylo-oligosaccharides obtained from
      hydrothermally treated Eucalyptus wood.
AB  - A combination of techniques was used to localise the O-acetyl substituents in
      xylo-oligosaccharides, which are present in hydrolysates of hydrothermally
      treated Eucalyptus wood. Reversed-phase (RP)-high performance liquid
      chromatography (HPLC) coupled on-line to both a mass spectrometer and an
      evaporating light scattering (ELS) detector provided data about the order of
      elution of the various O-acetylated oligomers. The retention of the oligomers on
      the column depended on the number and position of the O-acetyl substituents
      within the xylo-oligosaccharides. One dimensional (1D)- and two dimensional (2D)
      (1)H NMR spectroscopy was used to study the structural features of several
      xylotetramers separated by RP-HPLC, each having one O-acetyl substituent. O
      Acetyl migration was proven to have occurred in these xylo-oligosaccharides.
      Mainly O-acetyl migration within the same xylosyl residue was observed. RP-HPLC
      NMR was performed in order to study the structural features of the acetylated
      oligomers 'on-line' avoiding O-acetyl migration. Finally, the precise location of
      the 2-O- or 3-O-acetyl substituent in 6 xylotetramers and 4 xylotrimers separated
      by RP-HPLC was determined.

PMID- 12504384
TI  - UV monitoring of sugars during wine making.
AB  - A UV/UV system for the spectrophotometric determination of sugars during wine
      production is described. The methodology is based on the formation of a UV
      absorbing byproduct produced by the photodegradation of sugars. Under the given
      experimental conditions, the influence of increasing the amount of acids and
      alcohol is negligible. The measurement by UV/UV is compared with FTIR as
      reference method and validated according to the French norm AFNOR XPT 90 210.

PMID- 12504385
TI  - The absolute configuration of 1-carboxyethyl substituents on common hexoses by
      circular dichroism.
AB  - Determination of the absolute configuration of the 1-carboxyethyl substituent on
      a monosaccharide by circular dichroism measurements was found to be a sensitive
      and simple method. It relies on comparison of the spectrum of a 1-carboxyethyl
      substituted sugar or sugar derivative with the spectra of (R)- and (S)-lactic
      acid in the region 200-260 nm in which the (R)- and (S)-configuration give
      negative and positive deltaepsilon, respectively. The oligo- or poly-saccharide
      containing a 1-carboxyethyl substituted sugar is hydrolyzed to monomers and the 1
      carboxyethyl substituted sugar isolated by chromatography. The CD spectrum
      obtained for the 1-carboxyethyl substituted sugar in water solution at pH 2 is
      then compared with spectra of (R)- and (S)-lactic acid. The sign for the
      absorption and a maximum of comparable intensity and appearance around 210 nm,
      identify the stereochemistry.

PMID- 12504386
TI  - Depicting the MM3 potential energy surfaces of trisaccharides by single contour
      maps: application to beta-cellotriose and alpha-maltotriose.
AB  - The adiabatic potential energy surfaces (PES) of two trisaccharides (beta
      cellotriose and alpha-maltotriose) were obtained using the MM3 force field. Each
      PES can be described by a single 3D contour map for which the energy is plotted
      against the two psi glycosidic angles. Given the usually small variations of the
      phi glycosidic torsional angle in the low-energy regions of disaccharide maps (at
      least with MM3), it is valid to leave both phi glycosidic angles to relax in the
      process of building the conformational map of trisaccharides. The surfaces are
      those expected from the map of disaccharides containing the same linkages and
      monosaccharide units (i.e., beta-cellobiose and alpha-maltose), with second-order
      factors altering the 'symmetry' of both linkages. A large low-energy region
      appears for beta-cellotriose, comprising four minima in close proximity, with
      barriers between them below 0.6 kcal/mol. On the other hand, for alpha
      maltotriose a main global minimum is observed, with several surrounding local
      minima. The surfaces obtained agree with single-crystal X-ray data on these
      trisaccharides and derivatives. A reduction of the linkage flexibilities is
      observed when passing from the disaccharides to the trisaccharides. Furthermore,
      the linkage closer to the reducing end appears to be less flexible than the
      linkage closer to the non-reducing end.

PMID- 12504387
TI  - A simple method for preparation of D-rhamnose.
AB  - A rapid procedure for the preparation of D-rhamnose from bacterial
      lipopolysaccharide (LPS) has been developed. It involves purification of LPS from
      Pseudomonas syringae pv. phaseolicola by phenol extraction and hydrophobic
      interaction chromatography (HIC), followed by mild hydrolysis and cleavage of the
      O-antigen into D-fucose and D-rhamnose. The monosaccharides were separated by
      column chromatography, and D-rhamnose recovered after filtration over Sephadex-LH
      20.

PMID- 12504388
TI  - The rights and wrongs of WHO's policy of censorship.

PMID- 12504389
TI  - Hormones for coronary disease-full circle.

PMID- 12504390
TI  - Death and dignity: dogma disputed.

PMID- 12504391
TI  - Antimalarial cocktails--tropical flavours of the month.

PMID- 12504392
TI  - Type I diabetes: a role for tissue factor in pancreatic islet transplantation?

PMID- 12504393
TI  - Two Ps better than one?

PMID- 12504394
TI  - Medicine and conflict.

PMID- 12504395
TI  - Oestrogen therapy for prevention of reinfarction in postmenopausal women: a
      randomised placebo controlled trial.
AB  - BACKGROUND: Results of observational studies suggest that hormone replacement
      therapy (HRT) could reduce the risk of coronary heart disease (CHD), but those of
      randomised trials do not indicate a lower risk in women who use oestrogen plus
      progestagen. The aim of this study was to ascertain whether or not unopposed
      oestrogen reduces the risk of further cardiac events in postmenopausal women who
      survive a first myocardial infarction. METHODS: The study was a randomised,
      blinded, placebo controlled, secondary prevention trial of postmenopausal women,
      age 50-69 years (n=1017) who had survived a first myocardial infarction.
      Individuals were recruited from 35 hospitals in England and Wales. Women received
      either one tablet of oestradiol valerate (2 mg; n=513) or placebo (n=504), daily
      for 2 years. Primary outcomes were reinfarction or cardiac death, and all-cause
      mortality. Analyses were by intention-to-treat. Secondary outcomes were uterine
      bleeding, endometrial cancer, stroke or other embolic events, and fractures.
      FINDINGS: Frequency of reinfarction or cardiac death did not differ between
      treatment groups at 24 months (rate ratio 0.99, 95% CI 0.70-1.41, p=0.97).
      Similarly, the reduction in all-cause mortality between those who took oestrogen
      and those on placebo was not significant (0.79, 0.50-1.27, p=0.34). The relative
      risk of any death (0.56, 0.23-1.33) and cardiac death (0.33, 0.11-1.01) was
      lowest at 3 months post-recruitment. INTERPRETATION: Oestradiol valerate does not
      reduce the overall risk of further cardiac events in postmenopausal women who
      have survived a myocardial infarction.

PMID- 12504396
TI  - Ultrasonography in the diagnosis and management of developmental hip dysplasia
      (UK Hip Trial): clinical and economic results of a multicentre randomised
      controlled trial.
AB  - BACKGROUND: Clinical screening aims to identify and treat neonatal hip
      instability associated with increased risk of hip displacement, but risks
      failures of diagnosis and treatment (abduction splinting), iatrogenic effects,
      and costs to parents and health services. Our objectives were to assess clinical
      effectiveness and net cost of ultrasonography compared with clinical assessment
      alone, to provide guidance for management of infants with clinical hip
      instability. METHODS: Infants with clinical hip instability were recruited from
      33 centres in UK and Ireland and randomised to either ultrasonographic hip
      examination (n=314) or clinical assessment alone (n=315). The primary outcome was
      appearance on hip radiographs by 2 years. Secondary outcomes included surgical
      treatment, abduction splinting, level of mobility, resource use, and costs.
      Analysis was by intention to treat. FINDINGS: Protocol compliance was high, and
      radiographic information was available for 91% of children by 12-14 months and
      85% by 2 years. By age 2 years, subluxation, dislocation, or acetabular dysplasia
      were identified by radiography on one or both hips of 21 children in each of the
      groups (relative risk 1.00; 95% CI 0.56-1.80). Fewer children in the
      ultrasonography group had abduction splinting in the first 2 years than did those
      in the no-ultrasonography group (0.78; 0.65-0.94; p=0.01). Surgical treatment was
      required by 21 infants in the ultrasonography group (6.7%) and 25 (7.9%) in the
      no-ultrasonography group (0.84; 0.48-1.47). One child from the ultrasonography
      group and four from the no-ultrasonography group were not walking by 2 years
      (0.25; 0.03-2.53; p=0.37). Infants in the ultrasonography group incurred
      significantly higher ultrasound costs over the first 2 years (pound 42 vs pound
      23, mean difference pound 19, 95% CI 11-27); total hospital costs were lower for
      those infants, but the difference was not significant. INTERPRETATION: The use of
      ultrasonography in infants with screen-detected clinical hip instability allows
      abduction splinting rates to be reduced, and is not associated with an increase
      in abnormal hip development, higher rates of surgical treatment by 2 years of
      age, or significantly higher health-service costs.

PMID- 12504397
TI  - Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double
      blind, randomised, multicentre trial.
AB  - BACKGROUND: Treatment options for patients with secondary progressive multiple
      sclerosis are few. Encouraging results in open-label studies prompted this
      randomised trial of mitoxantrone in such patients. METHODS: 194 patients with
      worsening relapsing-remitting or secondary progressive multiple sclerosis were
      assigned placebo or mitoxantrone (5 mg/m(2) [exploratory group] or 12 mg/m(2)
      intravenously) every 3 months for 24 months. Clinical assessments were made every
      3 months for 24 months. The primary endpoint was a multivariate analysis of five
      clinical measures. Analyses of mitoxantrone 12 mg/m(2) versus placebo were based
      on patients who received at least one dose and returned for at least one
      assessment of efficacy. FINDINGS: Of 194 patients enrolled, 188 were able to be
      assessed at 24 months. There were no drug-related serious adverse events or
      evidence of clinically significant cardiac dysfunction. At 24 months, the
      mitoxantrone group experienced benefits compared with the placebo group for the
      primary outcome (difference 0.30 [95% CI 0.17-0.44]; p<0.0001) and the preplanned
      univariate analyses of those measures: change in expanded disability status scale
      (0.24 [0.04-0.44]; p=0.0194), change in ambulation index (0.21 [0.02-0.40];
      p=0.0306), adjusted total number of treated relapses (0.38 [0.18-0.59];
      p=0.0002), time to first treated relapse (0.44 [0.20-0.69]; p=0.0004), and change
      in standardised neurological status (0.23 [0.03-0.43]; p=0.0268). INTERPRETATION:
      Mitoxantrone 12 mg/m(2) was generally well tolerated and reduced progression of
      disability and clinical exacerbations. Further studies are needed to identify the
      patients with these forms of multiple sclerosis who are most likely to respond to
      therapy, the best treatment protocols, and the frequency of long-term drug
      related side-effects.

PMID- 12504398
TI  - Dignity in the terminally ill: a cross-sectional, cohort study.
AB  - BACKGROUND: Considerations of dignity are often raised in reference to the care
      of dying patients. However, little research that addresses this issue has been
      done. Our aim was to identify the extent to which dying patients perceive they
      are able to maintain a sense of dignity, and to ascertain how demographic and
      disease-specific variables relate to the issue of dignity in these individuals.
      METHODS: We did a cross-sectional study of a cohort of terminally ill patients
      with cancer, who had a life expectancy of less than 6 months. We enrolled 213
      patients from two palliative care units in Winnipeg, Canada, and asked them to
      rate their sense of dignity. Our main outcome measures included: a 7-point sense
      of dignity item; the symptom distress scale; the McGill pain questionnaire; the
      index of independence in activities of daily living (IADL); a quality of life
      scale; a brief battery of self-report measures, including screening for desire
      for death, anxiety, hopelessness, and will to live; burden to others; and
      requirement for social support. FINDINGS: 16 of 213 patients (7.5%; 95% CI 4-11)
      indicated that loss of dignity was a great concern. These patients were far more
      than likely than the rest of the cohort to report psychological distress and
      symptom distress, heightened dependency needs, and loss of will to live.
      INTERPRETATION: Loss of dignity is closely associated with certain types of
      distress often seen among the terminally ill. Preservation of dignity should be
      an overall aim of treatment and care in patients who are nearing death.

PMID- 12504399
TI  - Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment
      of uncomplicated malaria: a longitudinal randomised trial.
AB  - BACKGROUND: New antimalarial treatments are urgently needed in sub-Saharan
      Africa. Improved therapies should decrease failure rates in the short term, but
      their effect on incidence of subsequent episodes of malaria is little studied. We
      aimed to compare the short-term and long-term effectiveness of three antimalarial
      regimens in children from Kampala, Uganda. METHODS: We randomly allocated healthy
      children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg
      pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate.
      Participants were followed up for 1 year and received the same preassigned
      treatment for every new episode of uncomplicated malaria diagnosed during follow
      up. Recrudescent and new infections were distinguished by comparison of
      polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the
      total number of treatments for malaria per time at risk. Analyses were done per
      protocol. FINDINGS: 183 (61%) of 316 participants were diagnosed with at least
      one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated
      Plasmodium falciparum malaria were treated with study drugs; all regimens were
      safe and well tolerated. Clinical treatment failure after 14 days was
      significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215,
      18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group
      (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group
      (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the
      sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely
      to develop malaria than were those in the other groups. Overall,
      sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent
      treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/
      pyrimethamine alone and by 37% (12-54, p=0.007) compared with
      sulfadoxine/pyrimethamine plus artesunate. INTERPRETATION:
      Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive
      regimen to decrease the rate of subsequent episodes of malaria.

PMID- 12504400
TI  - Congenital absence of the left pericardium.

PMID- 12504401
TI  - Production of tissue factor by pancreatic islet cells as a trigger of detrimental
      thrombotic reactions in clinical islet transplantation.
AB  - BACKGROUND: Intraportal transplantation of pancreatic islets offers improved
      glycaemic control and insulin independence in type 1 diabetes mellitus, but
      intraportal thrombosis remains a possible complication. The thrombotic reaction
      may explain why graft loss occurs and islets from more than one donor are needed,
      since contact between human islets and ABO-compatible blood in vitro triggers a
      thrombotic reaction that damages the islets. We investigated the possible
      mechanism and treatment of such thrombotic reactions. METHODS: Coagulation
      activation and islet damage were monitored in four patients undergoing clinical
      islet transplantation according to a modified Edmonton protocol. Expression of
      tissue factor (TF) in the islet preparations was investigated by
      immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To
      assess TF activity in purified islets, human islets were mixed with non
      anticoagulated ABO-compatible blood in tubing loops coated with heparin.
      FINDINGS: Coagulation activation and subsequent release of insulin were found
      consistently after clinical islet transplantation, even in the absence of signs
      of intraportal thrombosis. The endocrine, but not the exocrine, cells of the
      pancreas were found to synthesise and secrete active TF. The clotting reaction
      triggered by pancreatic islets in vitro could be abrogated by blocking the active
      site of TF with specific antibodies or site-inactivated factor VIIa, a candidate
      drug for inhibition of TF activity in vivo. INTERPRETATION: Blockade of TF
      represents a new therapeutic approach that might increase the success of islet
      transplantation in patients with type 1 diabetes, in terms of both the risk of
      intraportal thrombosis and the need for islets from more than one donor.

PMID- 12504402
TI  - Cerebellar oedema and sideroblastic anaemia.

PMID- 12504403
TI  - Association of neural tube defects and folic acid food fortification in Canada.
AB  - Many women do not receive folic acid supplements before conception. In response,
      most of Canada's cereal grain products were being fortified with folic acid by
      January, 1998, thereby providing an additional 0.1-0.2 mg per day of dietary
      folate to the Canadian population. We assessed the effect of supplementation on
      prevalence of open neural tube defects in the province of Ontario. Among 336 963
      women who underwent maternal serum screening over 77 months, the prevalence of
      open neural tube defects declined from 1.13 per 1000 pregnancies before
      fortification to 0.58 per 1000 pregnancies thereafter (prevalence ratio 0.52, 95%
      CI 0.40-0.67, p<0.0001). At a population level, folic acid food fortification is
      associated with a pronounced reduction in open neural tube defects.

PMID- 12504405
TI  - Coalition aims to boost uptake of antiretroviral drugs.

PMID- 12504404
TI  - Pringle's manoeuvre in living donors.
AB  - The safety of the donor is paramount in living donor liver transplantation. The
      most important risk to the donor during hepatectomy is bleeding, and the inflow
      occlusion technique (Pringle's manoeuvre) has been reported to decrease bleeding
      without inducing liver injury in liver surgery. However, most transplant centres
      are doing donor hepatectomies without this technique for fear that it would
      result in ischaemic injury to the graft. We have done 46 living donor
      hepatectomies with Pringle's manoeuvre without any negative outcome on the
      quality of the graft. Surgeons should not hesitate to apply this technique in
      living donor hepatectomy.

PMID- 12504406
TI  - South African government "coming round" on AIDS drugs, Mandela says.

PMID- 12504407
TI  - Gene may have a role in cancer development by regulating angiogenesis.

PMID- 12504408
TI  - Passengers implicated in gastroenteritis outbreaks on cruise ships.

PMID- 12504409
TI  - Steroidal oestrogens added to list of known human carcinogens.

PMID- 12504410
TI  - Transgenic silkworms spin human collagen.

PMID- 12504411
TI  - Meningitis in Africa--tackling W135.

PMID- 12504413
TI  - PAHO exposes tobacco-industry tactics in Latin America. Pan American Health
      Organization.

PMID- 12504412
TI  - Homeland security is good and bad news for US science.

PMID- 12504414
TI  - Kenyan health professionals participate in female circumcision.

PMID- 12504415
TI  - Minister "ashamed" at malnutrition in Argentina.

PMID- 12504416
TI  - Country gardens.

PMID- 12504417
TI  - The portrait of breast cancer and Raphael's La Fornarina.

PMID- 12504418
TI  - "-but who is that on the other side of you?" Extracampine hallucinations
      revisited.

PMID- 12504419
TI  - An unusual, presumably hepatic mass.

PMID- 12504420
TI  - Street children and child labour around the world.

PMID- 12504421
TI  - Unravelling the fetal origins hypothesis.

PMID- 12504422
TI  - Unravelling the fetal origins hypothesis.

PMID- 12504423
TI  - Unravelling the fetal origins hypothesis.

PMID- 12504424
TI  - Unravelling the fetal origins hypothesis.

PMID- 12504426
TI  - Twins and the fetal origins hypothesis.

PMID- 12504427
TI  - Review of the spongiform encephalopathy advisory committee.

PMID- 12504428
TI  - Dietary control of phenylketonuria.

PMID- 12504429
TI  - Dietary control of phenylketonuria.

PMID- 12504430
TI  - Inhaled ethyl nitrite gas for persistent pulmonary hypertension in infants.

PMID- 12504432
TI  - Obstructive sleep apnoea.

PMID- 12504434
TI  - ASPECT-2 study.

PMID- 12504435
TI  - Obstructive sleep apnoea.

PMID- 12504436
TI  - Obstructive sleep apnoea.

PMID- 12504437
TI  - Prediction of colorectal cancer by consultation questionnaire.

PMID- 12504438
TI  - Prediction of colorectal cancer by consultation questionnaire.

PMID- 12504440
TI  - Should amalgam fillings be removed?

PMID- 12504441
TI  - Should amalgam fillings be removed?

PMID- 12504442
TI  - Thyroid-stimulating-hormone concentrations and risk of hypothyroidism.

PMID- 12504443
TI  - Thyroid-stimulating-hormone concentrations and risk of hypothyroidism.

PMID- 12504445
TI  - Peripheral-blood or bone-marrow mononuclear cells for therapeutic angiogenesis?

PMID- 12504446
TI  - Peripheral-blood or bone-marrow mononuclear cells for therapeutic angiogenesis?

PMID- 12504448
TI  - IL12B promoter polymorphism and asthma.

PMID- 12504449
TI  - 1L12B promoter polymorphism and asthma.

PMID- 12504451
TI  - TARGET follow-up study.

PMID- 12504453
TI  - ICON3 and chemotherapy for ovarian cancer.

PMID- 12504454
TI  - ICON3 and chemotherapy for ovarian cancer.

PMID- 12504455
TI  - ICON3 and chemotherapy for ovarian cancer.

PMID- 12504457
TI  - Hepatitis C virus in people with HIV infection.

PMID- 12504459
TI  - W135 meningococcal carriage in Hajj pilgrims.

PMID- 12504460
TI  - Ergonomic pathology of Luigi Boccherini.

PMID- 12504480
TI  - Building a global culture of science.

PMID- 12504481
TI  - Japanese doctors' experimentation in wartime China.

PMID- 12504482
TI  - Nurses in war.

PMID- 12504483
TI  - Reflections on military medicine.

PMID- 12504484
TI  - Child combatants: a soldier's perspective.

PMID- 12504485
TI  - Gender-based violence in refugee settings.

PMID- 12504486
TI  - Reproductive health for refugees.

PMID- 12504487
TI  - Rape and HIV/AIDS in Rwanda.

PMID- 12504488
TI  - HIV and tuberculosis in the former Soviet Union.

PMID- 12504489
TI  - Sudan's war and eradication of dracunculiasis.

PMID- 12504490
TI  - Deadly comrades: war and infectious diseases.

PMID- 12504491
TI  - Health as a bridge for peace: PAHO's experience. Pan American Health
      Organization.

PMID- 12504492
TI  - Food shortages and nutrition in North Korea.

PMID- 12504493
TI  - Water: life force or instrument of war?

PMID- 12504494
TI  - Depleted uranium: a new battlefield hazard.

PMID- 12504495
TI  - The reality of the modern bioterrorism response.

PMID- 12504496
TI  - Long-term effects of chemical weapons.

PMID- 12504497
TI  - World Trade Center cough.

PMID- 12504498
TI  - Ambiguous loss in families of the missing.

PMID- 12504499
TI  - Addressing mental health in Afghanistan.

PMID- 12504500
TI  - Psychosocial needs in complex emergencies.

PMID- 12504501
TI  - Hearing the voices: mental health services in East Timor.

PMID- 12504502
TI  - Older refugees in humanitarian emergencies.

PMID- 12504503
TI  - Access to health care in the Western Cape.

PMID- 12504504
TI  - Democratic health care for a democratic Kosovo.

PMID- 12504505
TI  - Punishment beatings and the rule of law.

PMID- 12504506
TI  - Caring and advocating for victims of torture.

PMID- 12504507
TI  - Rebirth of the health-care system in Cambodia.

PMID- 12504508
TI  - What can medical journal editors do in war?

PMID- 12504509
TI  - Photopolymerized hyaluronic acid-based hydrogels and interpenetrating networks.
AB  - Hyaluronic acid (HA) was derivatized with methacrylic esters used for the
      preparation of hydrogels via photopolymerization. Poly(ethylene glycol)
      diacrylate (PEG-DA) with a molecular weight of 570 was also used as a
      comacromonomer to improve elastic modulus and swelling behavior. The hydrogels
      were readily degraded by hyaluronidase and their mechanical properties could be
      modulated by HA molecular weight and concentration of PEG-DA. The incorporation
      of RGD peptides allowed modulation of the HA properties from cell non-adhesive to
      adhesive. Human dermal fibroblasts were cultured on the RGD, RDG, and non
      functionalized HA hydrogels for up to 7d, showing adhesion and proliferation only
      with incorporated RGD.

PMID- 12504510
TI  - Biological activities of osteoblasts on poly(methyl methacrylate)/silica hybrid
      containing calcium salt.
AB  - The biological activity of osteoblasts on the newly developed bioactive
      poly(methyl methacrylate) (PMMA)/silica hybrid containing calcium salt was
      investigated. The attachment, proliferation, and differentiation of primary
      cultured mouse calvarial osteoblasts were evaluated by hexosaminase, MTT, and
      alkaline phosphatase activity assays, respectively. The PMMA/silica hybrid showed
      higher biological activities than those of pure PMMA with regard to all three
      parameters. Besides, the calcium phosphate layer, determined by scanning electron
      microscopy with energy dispersive spectroscopy, occurred only on the PMMA/silica
      hybrid. Better biological activities on the PMMA/silica hybrid than those on the
      PMMA were explained by the role of calcium phosphate layer formed on the
      PMMA/silica hybrid and the released calcium and silicon ions from it during the
      cell culture. These results suggest that the PMMA/silica hybrid might be useful
      as a bone substitute or filler.

PMID- 12504511
TI  - Electrospinning of poly(ethylene-co-vinyl alcohol) fibers.
AB  - Solutions of poly(ethylene-co-vinyl alcohol) or EVOH, ranging in composition from
      56 to 71 wt% vinyl alcohol, can be readily electrospun at room temperature from
      solutions in 70% 2-propanol/water (rubbing alcohol). The solutions are prepared
      at 80 degrees C and allowed to cool to room temperature. Interestingly, the
      solutions are not stable at room temperature and eventually the polymer
      precipitates after several hours. However, prior to precipitation,
      electrospinning is extensive and rapid, allowing coverage of fibers on various
      substrates, including a grounded metal plate, dielectrics interposed between the
      charged jet and the metal ground, and on the human body. Fiber diameters of ca.
      0.2-8.0 microm were obtained depending upon the solution concentration, an
      attractive range for tissue engineering, wound healing, and related applications.
      Electrospun EVOH mats have been shown to support the culturing of smooth muscle
      cells and fibroblasts.

PMID- 12504512
TI  - The use of hyaluronan and its sulphated derivative patterned with micrometric
      scale on glass substrate in melanocyte cell behaviour.
AB  - Surface microfabrication techniques were widely utilised for the spatial control
      of in vitro cell behaviour. A photo-immobilisation procedure was utilised to
      create micropatterned surfaces: four different stripe patterns (100, 50, 25 and
      10 microm) of hyaluronan (Hyal) and its sulphated derivative (HyalS) on silanised
      glass substrate were obtained.The morphological analysis showed that the surface
      topography showed regular stripes of 100, 50, 25 and 10 microm wide and ranging
      from 300 nm up to 1 microm in thickness. They reproduced the exact photo-mask
      pattern: glass stripes alternating with polysaccharide ones. On the contrary,
      Hyal microstructures showed just a topographic pattern as the glass stripes
      appeared to be covered by a thin layer of the macromolecule by TOF-SIMS. Cell
      adhesion studies demonstrated that melanocytes adhered and oriented within the
      first 2h of culture on HyalS microdomains and not on Hyal microstructures where
      they spread on glass substrate around the patterned area. Double photo
      immobilised samples characterised by a 100 microm stripe pattern of Hyal or HyalS
      on the top of a continuous layer of the two polysaccharides were also created in
      order to investigate the effect of the topography on cell behaviour. The obtained
      results demonstrated that melanocytes adhered on HyalS stripes while on the Hyal
      micropatterned surfaces they spread on silanised glass substrate around the
      structured area, resulting in the exclusion of the topographic pattern.

PMID- 12504513
TI  - Fibroblast reaction to island topography: changes in cytoskeleton and morphology
      with time.
AB  - In order to develop next-generation tissue engineering materials, the
      understanding of cell responses to novel material surfaces needs to be better
      understood. Topography presents powerful cues for cells, and it is becoming clear
      that cells will react to nanometric, as well as micrometric, scale surface
      features. Polymer-demixing of polystyrene and polybromostyrene has been found to
      produce nanoscale islands of reproducible height, and is very cheap and fast
      compared to techniques such as electron beam lithography. This study observed
      temporal changes in cell morphology and actin and tubulin cytoskeleton using
      scanning electron and fluorescence microscopy. The results show large differences
      in cell response to 95 nm high islands from 5 min to 3 weeks of culture. The
      results also show a change in cell response from initial fast organisation of
      cytoskeleton in reaction to the islands, through to lack of cell spreading and
      low recruitment of cell numbers on the islands.

PMID- 12504514
TI  - Fabrication of HAp-ZrO2 (3Y) nano-composite by SPS.
AB  - Nano-HAp-ZrO(2) powders and HAp-TZP(3Y) composites have been fabricated in this
      work. The results show that nano-HAp-ZrO(2) powders with homogeneous distribution
      could be synthesized by two-step precipitation method. HAp-TZP(3Y) composites
      with small grain size could be sintered at relatively low temperatures and very
      short dwelling time by using SPS technology. No reaction between HAp and ZrO(2)
      was found, which could be attributed to the very short sintering time of SPS.

PMID- 12504515
TI  - Effect of bone-like layer growth from culture medium on adherence of osteoblast
      like cells.
AB  - The electrical polarization of ceramic HAp had an effect on the acceleration of
      bone restoration. Cell behavior in the bone-like growth layer was investigated.
      The deposits on the ceramic HAp was grown and formed layers by soaking in alpha
      minimum essential medium supplemented with 10% fetal bovine serum (alpha-MEM
      supplemented with 10% FBS). The shapes of the adhering cells on the grown layer
      gradually changed from spindle to flat with growth of the layer. On the totally
      grown layer that was grown on the ceramic HAp by soaking in alpha-MEM
      supplemented with 10% FBS for 7 days, all the adhering cells were flat and the
      surface was filled with the grown cells. From these results, it was revealed that
      the grown layer on the ceramic HAp is one of the activation factors of cell
      growth. Consequently, cell growth was reinforced by acceleration of the layer
      growth on the negatively charged surface of the polarized ceramic HAp.

PMID- 12504516
TI  - Impact formation and microstructure characterization of thermal sprayed
      hydroxyapatite/titania composite coatings.
AB  - Formation mechanism of hydroxyapatite (HA)/titania (TiO(2)) composite coating
      deposited by high velocity oxy-fuel (HVOF) thermal spray process was studied, and
      its structural characterization was conducted and elaborated in this paper. The
      impact theory was employed to analyze the formation procedure of the HA/titania
      composite coatings. Results revealed that the crater caused by the impact of
      entirely unmelted TiO(2) particles on the HA matrix during coating formation was
      of smaller dimensions than the original size of the reinforcements. It was found
      that chemical reaction between the mechanically blended HA and TiO(2) powder took
      place exclusively during the impingement stage, and calcium titanate, CaTiO(3),
      was one notable by-product. The bonding between the HA matrix and TiO(2)
      reinforcement might have been achieved predominantly through a chemical bond that
      resulted from the mutual chemical reactions among the components. Differential
      scanning calorimetry analyses showed that the chemical reaction between HA and
      TiO(2) was at approximately 1410 degrees C. The TiO(2) addition was found to
      exert particular effects on the thermal behavior of HA at elevated temperatures,
      during both heating and cooling cycles. Transmission electron microscopy
      observation identified the chemical reaction zone between HA and TiO(2), which
      revealed an improved splats' interface. The reaction zone demonstrated some
      influence on the grain size of HA nearby during resolidification of the melted
      portion. A structural model was proposed to illustrate the location of the
      different phases in the HA/titania composite coating.

PMID- 12504517
TI  - Immuno-allergological properties of aluminium oxide (Al2O3) ceramics and nickel
      sulfate in humans.
AB  - For more than 30 years aluminium oxide (Al(2)O(3)) ceramics have been used for
      implants in maxillofacial and orthopaedic surgery. Up to now, there are no
      reports and also no investigations on hypersensitivity reactions. In order to
      evaluate the aspects of immuno-allergological reactivity to aluminium oxide
      ceramics, skin testing and in vitro lymphocyte activation studies were performed.
      The patch test reactivity to a standard series of contact allergens and to an
      aluminium oxide (Al(2)O(3)) disk was examined in a consecutive series of 250
      patients frequenting a University Dermatology Clinic. Furthermore, peripheral
      blood mononuclear cells (PBMC) of 15 nickel-allergic and 15 non-allergic
      individuals were cultured with medium alone, with the pan T-cell mitogen
      phytohemagglutinine (PHA) or with nickel sulfate (NiSO(4)). By additional
      presence/absence of Al(2)O(3) disk its influence on the cytokine secretion
      pattern and proliferative response was investigated. The results show that in
      contrast to a high frequency of delayed-type hypersensitivity to standard contact
      allergens, no allergic skin reactions to Al(2)O(3) ceramics occured. The IL-4 and
      IFN-gamma production in vitro remained almost unchanged by the presence of
      Al(2)O(3) disk as well as the proliferative response of PBMC of non-allergic
      individuals. Cellular reactivity of nickel allergic and non-allergic donors was
      partly enhanced upon contact to Al(2)O(3) disks.

PMID- 12504518
TI  - Surface modification of tricalcium phosphate for improvement of the interfacial
      compatibility with biodegradable polymers.
AB  - The surface of tricalcium phosphate (TCP) filler particles was activated by
      treatment with dilute aqueous phosphoric acid. ATR-IR spectra indicated the
      formation of calcium hydrogen phosphate dihydrate at the surface. Oligo(lactone)s
      were formed by the subsequent reaction of the activated TCP with L-lactide and
      epsilon -caprolactone, respectively, at 150 degrees C without any additional
      catalysts. After extraction of the oligo(lactide), the residue of modified TCP
      included calcium lactate whereas the water of crystallization of the dihydrate
      disappeared as shown by ATR-IR spectroscopy. Owing to the insolubility of TCP in
      common solvents, the analogous reaction between water-soluble disodium hydrogen
      phosphate dihydrate and L-lactide was used to study the kind of chemical bonds by
      high-resolution NMR spectroscopy. The 1H and 13C NMR spectra of the reaction
      product also pointed out the presence of calcium lactate. Additionally, signals
      were found indicating a covalent attachment of lactic acid units onto the
      phosphorus. For the preparation of composites, poly(L,DL-lactide) was mixed with
      TCP and modified TCP, respectively, in a ratio of 75/25 (w/w) and directly
      injection moulded into tensile test specimens at a barrel temperature of 180
      degrees C. Although mechanical properties were not improved, scanning electron
      microscopy (SEM) indicated a better interfacial phase interaction in the
      composite with the modified TCP. Chemical bonds between filler and polymer matrix
      are assumed to be formed by transesterification reactions.

PMID- 12504519
TI  - Diffusion coefficient of water through dental composite resin.
AB  - Water sorption of polymer filling materials affects dimensional stability,
      mechanical properties and bonding strength with tooth structures. To clarify the
      effect of the degradation on service life and micro-leakage, the diffusion
      coefficient of water through the resin should be identified. Distributions of
      time-dependent water concentrations in the resin were computed. Water sorption of
      composite resin discs with different thicknesses was measured and compared with
      the solution of Fick's second law. The diffusion coefficient of water through the
      resin discs was computed to be D=3.9-5.0 x 10(-13)m(2)/s from the measurements of
      specimens with different thicknesses. Results of water sorption measurements for
      the discs with different thicknesses were in good agreement with the theoretical
      results. The relationship among the thickness of the disc, the diffusion
      coefficient and the water sorption ratio was shown clearly. The testing method
      for water sorption by International Standard ISO 4049 for resin-based filling
      materials was discussed.

PMID- 12504520
TI  - Mercuric chloride: toxicity and apoptosis in a human oligodendroglial cell line
      MO3.13.
AB  - A human-human oligodendroglial cell line MO3.13 was chosen in this study to model
      the loss of oligodendrocytes that occurs during episodes of multiple sclerosis.
      The influence of mercuric chloride (HgCl(2)) upon cell viability specifically the
      mode of cell death, whether by an active apoptotic mechanism or passive necrosis
      was determined by morphological and biochemical analysis. Mitochondrial
      dehydrogenase activity MTT assay showed that HgCl(2) had toxic effects on MO3.13
      cells at levels of (5-25 microM) with approximately 50% cell death observed at 58
      microM. Death of cells was dependent on both time and concentrations of HgCl(2).
      Differentiated MO3.13 cells exposed to low concentrations (25 microM) of HgCl(2)
      exhibited features of apoptotic cell death, including cell shrinkage and
      chromatin condensation. High doses of HgCl(2) (>100 microM) induced death with
      characteristics of necrosis. Biochemical analysis showed that HgCl(2) activated
      the caspase family of proteases. This was measured directly by cleavage of
      fluorescent substrates and by immunoblotting assay of caspase substrate proteins;
      alpha-fodrin, lamin B and poly (ADP-ribose) polymerase (PARP). These results
      indicate that HgCl(2) is toxic at low concentrations for oligodendroglial cells
      and that the MO3.13 cell line dies in an apoptotic manner when exposed to low
      concentrations of HgCl(2). However, blood mercury concentrations in vivo in a
      normal population with amalgam restorations are lower by a factor of some 500
      times than those causing toxicity in vitro suggesting a good safety margin in
      respect of environmental uptake.

PMID- 12504521
TI  - Histological evaluation of the bone response to calcium phosphate cement
      implanted in cortical bone.
AB  - The aim of this study was to investigate the physicochemical and biological
      properties of a newly developed calcium phosphate cement (CaP cement) implanted
      in cortical bone. CaP cement was injected as a paste into tibia cortical bone
      defects in goats. Polymethylmethacrylate (PMMA) bone cement was used as a
      control. The animals were killed after 3 days, 2, 8, 16 and 24 weeks. X-ray
      diffraction and Fourier transform infrared spectroscopy performed at retrieved
      samples showed that the CaP cement had set as a carbonate apatite and remained
      stable over time. Light microscopic evaluation showed that after 2 weeks the
      cement was in tight contact with the bone without any inflammatory reaction or
      fibrous encapsulation. At later time points, the CaP cement implants were totally
      covered by a thin layer of bone and osteoclasts, present at the interface, which
      were clearly resorbing the cement. At locations where CaP cement was resorbed,
      new bone was deposited. Transmission electron microscopy revealed that indeed a
      seamless contact existed between CaP cement and bone, as characterized by the
      occurrence of an electron dense line of 50-60 nm thick that covered the CaP
      cement. Osteoblasts, in contact with the cement, were depositing new bone.
      Although the bulk of the material was still in situ after 24 weeks, the
      progressive osteoclast resorption of the cement followed by new bone formation
      suggests that all of the material may be replaced eventually. In contrast to the
      CaP cement, the PMMA reference cement was always surrounded by a thin fibrous
      capsule. The results indicate that the investigated CaP cement is biocompatible,
      osteoconductive as well as osteotransductive and is a candidate material for use
      as a bone substitute.

PMID- 12504522
TI  - Intracellular uptake of anionic superparamagnetic nanoparticles as a function of
      their surface coating.
AB  - A new class of superparamagnetic nanoparticles bearing negative surface charges
      is presented. These anionic nanoparticles show a high affinity for the cell
      membrane and, as a consequence, are captured by cells with an efficiency three
      orders of magnitude higher than the widely used dextran-coated iron oxide
      nanoparticles. The surface coating of anionic particle with albumin strongly
      reduces the non specific interactions with the plasma membrane as well as the
      overall cell uptake and at the same time restores the ability to induce specific
      interactions with targeted cells by the coadsorption on the particle surface of a
      specific ligand. Kinetics of cellular particle uptake for different cell lines
      are quantitated using two new complementary assays (Magnetophoresis and Electron
      Spin Resonance).

PMID- 12504523
TI  - The effect of two configuration factors, time, and thermal cycling on resin to
      dentin bond strengths.
AB  - Most in vitro testing of bonding systems is performed using specimens made in a
      mold with a low configuration (C) factor (ratio of bonded/unbonded surfaces)
      whereas clinically the C-factor is usually much greater. This study compared the
      effect of thermal cycling on the measured shear bond strength of 3M Single Bond
      dental adhesive bonded to dentin using molds with two different C-factors. The
      hypothesis was that neither C-factor nor thermal cycling would affect measured
      bond strengths. Resin composite was bonded to human dentin in cylindrical molds
      with an internal diameter of 3.2mm and either 1mm or 2.5mm deep. The 1mm deep
      molds had a C-factor of 2.2 and the 2.5mm deep molds had a C-factor of 4.1.
      Specimens were debonded either 10min after they had been bonded to dentin, or
      after they had been stored for 7 days in water at 37+/-1 degrees C, or after
      thermal cycling 5000 times for 7 days. Two-way ANOVA showed that overall both the
      C-factor and the storage condition had a significant effect on bond strength
      (p<0.001). There was a significant interaction (p<0.001) between the C-factor and
      how the specimens had been stored. The GLM/LSMEANS procedure with Sidak's
      adjustment for multiple comparisons showed that overall the specimens made in the
      mold with a high C-factor (4.1) had a lower bond strength than those that had
      been made in the mold with a lower (2.2) C-factor (p<0.001). Thermal cycling had
      a negative effect on the bond strength only for specimens made in molds with a C
      factor of 4.1 (p<0.001).

PMID- 12504524
TI  - Evaluation of the reaction kinetics of CORTOSS, a thermoset cortical bone void
      filler.
AB  - The primary objective of this research is to evaluate the reaction kinetics of
      CORTOSS(TM), a thermoset, Bis-GMA (2,2-bis[4-(2-hydroxymethacryloxypropyl)
      phenyl]propane) composite system as a function of time, material storage
      temperature and the temperature of the surrounding environment (site
      temperature). This study utilizes probability theory to predict the percentage of
      bifunctional monomers with 0,1 and 2 functional groups that have been reacted.
      This is a strong indicator of the potential for leaching unreacted components. A
      differential scanning calorimeter (DSC) was used to measure the isothermal
      enthalpy at varying site temperatures. After isothermal monitoring, the samples
      were dynamically heated from the respective isothermal temperature to 175 degrees
      C at 15 degrees C/min to measure the residual enthalpy from the unreacted
      functional groups. The experimental results indicate that the degree of
      conversion for this bifunctional system ranged from 76% to 86%. Applying
      probability theory it has been determined that approximately 95% of the
      bifunctional monomers are present with at least one double bond reacted and up to
      5% of monomers remain unreacted. This is consistent with theoretical values
      postulated for various diffusion controlled thermoset systems (Macromolecules 32
      (1999) 3913). Overall, curing under physiological conditions yielded a faster
      reaction rate and a significantly higher degree of conversion as compared to the
      lower site temperature conditions.

PMID- 12504525
TI  - Image analysis of the axonal ingrowth into poly(D,L-lactide) porous scaffolds in
      relation to the 3-D porous structure.
AB  - Porous polymer scaffolds are promising materials for neural tissue engineering
      because they offer valuable three-dimensional (3-D) supports for the in vitro and
      in vivo axonal growth and tissue expansion. At the time being, how the in vivo
      neuronal cell development depends on the scaffold 3-D architecture is unknown.
      Therefore, scanning electron micrographs of longitudinal sections of porous
      polylactide scaffolds and immunohistological sections of these scaffolds after
      implantation and neurofilament staining have been studied by image analysis. Pore
      orientation and axonal ingrowth have been investigated by spectral analysis on
      gray level SEM images. Binary image processing has been carried out and the
      binary images have been studied by spectral analysis in order to estimate the
      possible effect of the image noise on the real pattern. In addition to axonal
      orientation, density and length distribution of the regenerated axons into the
      polymer scaffold have been measured. Dependence of the axonal ingrowth on the 3D
      polymer scaffold has been discussed on the basis of the collected data.

PMID- 12504526
TI  - Polyhydroxyalkanoate (PHA) scaffolds with good mechanical properties and
      biocompatibility.
AB  - Blending microbial polyesters polyhydroxyalkanoates containing
      polyhydroxybutyrate (PHB) and poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx)
      were turned into films and scaffolds. The films made from blending polyesters
      showed that the elongation to break of the blending PHBHHx/PHB film increased
      from 15% to 106% when PHBHHx content in the blend increased from 40% to 60%.
      Scaffolds made of PHBHHx/PHB consisting of 60 wt% PHBHHx showed strong growth and
      proliferation of chondrocytes on the blending materials under scanning electron
      microscope. Energy dispersive X-ray analysis of the extra cellular matrix on the
      scaffolds demonstrated a high level of calcium and phosphorus elements in a molar
      ratio of Ca/P at 1.66, this is approximately equal to that of natural material
      hydroxyapatite which has a Ca/P ratio of 1.67. This suggested that the
      chondrocyte cells grown on PHBHHx/PHB scaffolds presented effective physiological
      function for generation of cartilage.

PMID- 12504527
TI  - Fabrication of a novel porous PGA-chitosan hybrid matrix for tissue engineering.
AB  - Polyglycolide (PGA) and chitosan mixture solution was prepared using solvents of
      low toxicity to create novel, porous, biocompatible, degradable, and modifiable
      hybrid matrices for biomedical applications. The porosity of these PGA-chitosan
      hybrid matrices (P/C matrices) was created by a thermally induced phase
      separation method. Two types of the P/C hybrid matrices containing 70 wt% PGA
      (P/C-1 matrix) and 30 wt% PGA (P/C-2 matrix) were fabricated. Chitosan matrix was
      also prepared for comparison. A 35-day in vitro degradation revealed that the
      weight losses for the P/C-1 and P/C-2 matrices were similar ( approximately 61%),
      but the releases of glycolic acid from the P/C-1 and P/C-2 matrices were 95% and
      60%, respectively. The P/C-1 matrix had higher porosity and higher mechanical
      strength than the P/C-2 and chitosan matrices. Fibroblast cells cultivated in
      these matrices proliferated well and the cell density was the highest in the P/C
      1 matrix, followed by the chitosan and P/C-2 matrices, suggesting good
      biocompatibility for the P/C-1 matrix. We thereby concluded that the P/C-1
      matrix, due to its high strength, porosity, biocompatibility and degradability,
      is a promising biomaterial. The presence of chitosan in the P/C matrices provides
      many amino groups for further modifications such as biomolecule conjugation and
      thus enhances the application potential of the P/C hybrid matrices in tissue
      engineering.

PMID- 12504528
TI  - MG63 osteoblastic cell adhesion to the hydrophobic surface precoated with
      recombinant osteopontin fragments.
AB  - The hydrophobicity of biomaterials has been recognized as a limitation to the
      adequate function of anchorage-dependent cells when hydrophobic biomaterials are
      used for tissue engineering. This is due to flawed solid-state signals from cell
      adhesion. In this study, a recombinant osteopontin (rOPN17-169) fragment
      containing the cell adhesion motifs was expressed in E. coli and was precoated on
      the hydrophobic surface prior to osteoblastic MG63 cell culture. Precoating the
      hydrophobic surface with rOPN17-169 improved osteoblastic cell adhesion, which
      was blocked by soluble RGDS. The adhesion of MG63 cells to rOPN17-169 pre-coated
      surface-activated mitogen-activated protein kinases (MAPK) such as extracellular
      signal-receptor kinase 1/2, p38, and c-Jun N-terminal kinase (JNK). In addition,
      p38 MAPK was activated in response to a soluble factor of transforming growth
      factor-beta in the cells adhered to the hydrophobic surface via rOPN17-169. This
      suggests that rOPN17-169 precoated on the hydrophobic surface can allow
      osteoblastic cells to generate adhesion signals sufficient for cell adhesion,
      MAPK activation, and the cytokine activation of osteoblastic cells.

PMID- 12504529
TI  - Structure and properties of bilayer chitosan-gelatin scaffolds.
AB  - Chitosan-gelatin hybrid polymer network scaffolds were prepared via the freeze
      drying technique by using the ice microparticle as a porogen. Monolayer and
      bilayer scaffolds were obtained by using different pre-freezing methods. The
      novel bilayer scaffolds were prepared via contact with -56 degrees C lyophilizing
      plate directly, then lyophilized. The properties of chitosan-gelatin scaffolds,
      such as microstructure, physical and mechanical and degradable properties, were
      studied. These results suggested that the porosity and pore size of the scaffolds
      could be modulated with thermodynamic and kinetic parameters of ice formation.
      The scaffolds prepared from chitosan and gelatin can be utilized as a promising
      matrix for tissue engineering.

PMID- 12504530
TI  - Surface effects and desorption of tetracycline supramolecular complex on bovine
      dentine.
AB  - The aim of this in vitro study was to evaluate the antimicrobial activity, the
      substantivity, and surface effects of the inclusion compound tetracycline: beta
      cyclodextrin on bovine roots. The antimicrobial activity was assessed by dentine
      slabs which had been immersed in the inclusion complex in concentrations 8.0%,
      4.0%, 2.0%, 1.0%, 0.5% and 0.25% for 5min compared to a control of tetracycline
      hydrochloride. Each slab was tested in a broth of overnight culture of
      Actinobacillus actinomycetemcomitans (Y4-FDC). The inclusion complex
      significantly inhibited the A. actinomycetemcomitans (p<0.01) verified at
      concentrations from 1.0% to 8.0%. The substantivity of tetracycline was evaluated
      by the measure of desorption from the slabs previously immersed in solution
      samples and removed at 24h intervals. The tetracycline encapsulated in beta
      cyclodextrin showed a flow rate near to zero order in comparison to free
      tetracycline. The surface morphology determined by SEM showed a more homogeneous
      and integrated layer with the complex compared to the effect of free
      tetracycline. We concluded that the root surfaces treated with tetracycline: beta
      cyclodextrin release lower concentrations of active drug over 5 days at
      inhibitory concentrations against A. actinomycetemcomitans with enhanced
      disponibility in comparison to tetracycline.

PMID- 12504531
TI  - Retrieval study of uncemented metal-metal hip prostheses revised for early
      loosening.
AB  - A tribologic assessment was performed on 22 metal-metal hip prostheses from a
      single manufacturer, following removal for early aseptic loosening after a mean
      service life of 32 months (range, 12-59 months). The mean linear wear rate was
      7.6 microm/year (range, 2.9-12.8 microm/year). This was below the rates
      previously observed in other modern metal-metal combinations. A novel contour
      analysis technique using a coordinate measuring machine showed the mean
      volumetric wear rate to be 2.02 mm(3)/year (range, 0.55-3.74 mm(3)/year), which
      corresponds to a mean gravimetric wear rate of 16.9 mg/year (range, 4.6-31.4
      mg/year). The mean clearance of 39.8 microm (range, 30-50 microm) was within the
      optimal range for hard-hard bearing combinations. Evidence of abrasive, adhesive,
      and third-body wear was found on all bearing surfaces. The tribologic assessment
      did not indicate manufacturing defects as a cause of early loosening. Equally,
      third-body wear was too low to be considered a causative factor for early
      loosening.

PMID- 12504532
TI  - Element release from titanium devices used in oral and maxillofacial surgery.
AB  - Optical microscopy, scanning electron microscopy and X-ray microanalysis (EDS
      system) were used on c.p. titanium devices (21 grids and 10 plates) removed from
      28 patients without signs of inflammation 6-24 months after surgery. Plates,
      grids and surrounding tissue were investigated to evaluate the titanium release
      and accumulation. Titanium was only present in the interfacial bone, probably due
      to fretting, and in all fibrous tissue surrounding the devices. Titanium content
      followed a decreasing gradient extending from the device surface and was not
      detected at a distance greater than 1mm. High titanium levels were found in blood
      cells in the connective tissue. In conclusion, titanium release from the devices
      stops only after bone is laid down on the titanium surfaces. Titanium release
      does not seem to interfere with the osteogenic process but perhaps may interact
      with it.

PMID- 12504533
TI  - Histological analysis of silicone breast implant capsules and correlation with
      capsular contracture.
AB  - BACKGROUND: A study was undertaken to investigate long-term histological changes
      in the environment of breast implants and their correlation with complains at the
      time of capsular contracture defined by the Baker score. METHOD: The collagenous
      capsules of 53 silicone breast implants from 43 patients (23 smooth and 30
      textured devices) were evaluated histologically for capsular thickness, the
      presence of histiocytes, the amount of silicone and calcification in the capsule,
      and the presence of synovial-like metaplasia of the inner surface of the capsule
      with light microscopy and polarised light. All parameters were correlated with
      the Baker score. RESULTS: A significantly higher degree of the Baker score was
      found with increasing patient age (p<0.001), implant duration (p<0.02), and
      capsular thickness (p<0.009). A trend towards greater capsular thickness was
      documented in patients who had a breast augmentation for cosmetic reasons.
      Synovial-like metaplasia was seen in 28 capsules (52.8%). The highest incidence
      was found in textured implants with a duration of less than 5 years. Histiocytic
      inflammation was more common in patients with clinical symptoms (p<0.001) and
      around subglandular implants (p<0.096). CONCLUSIONS: The histological findings of
      breast capsules were related to: the nature of the device surface (smooth versus
      textured), implant duration, and the degree of capsular contracture. Capsular
      contracture (Baker score of 3 or 4) was related to implant duration, capsule
      thickness, patient age, and inflammation.

PMID- 12504534
TI  - Effect of test frequency on the in vitro fatigue life of acrylic bone cement.
AB  - The goal of the present work was to test the hypothesis that test frequency, f,
      does not have a statistically significant effect on the in vitro fatigue life of
      an acrylic bone cement. Uniaxial constant-amplitude tension-compression fatigue
      tests were conducted on 12 sets of cements, covering three formulations with
      three very different viscosities, two different methods of mixing the cement
      constituents, and two values of f (1 and 10 Hz). The test results (number of
      fatigue stress cycles, N(f)) were analyzed using the linearized form of the three
      parameter Weibull equation, allowing the values of the Weibull mean (N(WM)) to be
      determined for each set. Statistical analysis of the lnN(f) data, together with
      an examination of the N(WM) estimates, showed support for the hypothesis over the
      range of f used. The principal use and explanation of the present finding are
      presented.

PMID- 12504535
TI  - Control of lymphocytic choriomeningitis virus infection in granzyme B deficient
      mice.
AB  - We have investigated whether granzyme B (GzmB) is required for effective
      cytotoxic T lymphocyte (CTL) mediated control of lymphocytic choriomeningitis
      virus (LCMV) infection. Clearance of LCMV from tissues of GzmB-deficient (GzmB-)
      mice following intraperitoneal infection with LCMV was impaired compared with
      control mice; however, the virus was ultimately eliminated. The impaired
      clearance of LCMV in GzmB- mice was not due to a deficiency in the generation of
      LCMV-specific T cells. In addition, CTL from LCMV-infected GzmB- mice efficiently
      lysed virus-infected cells in vitro, but were deficient in their ability to
      induce rapid DNA fragmentation in target cells. We examined whether the
      development of protective immunity against intracranial (i.c.) rechallenge with
      LCMV was compromised in GzmB- mice. We found that clearance of LCMV from the
      brain following secondary i.c. infection also was slower in the absence of GzmB;
      however, the virus was ultimately eliminated and the mice survived. Our data
      indicate that clearance of LCMV is delayed in the absence of GzmB expression, but
      that other CTL effector molecules can compensate for the absence of this granule
      constituent in vivo.

PMID- 12504536
TI  - Analysis of RNA packaging in wild-type and mosaic protein capsids of flock house
      virus using recombinant baculovirus vectors.
AB  - Flock house virus (FHV) is a small icosahedral insect virus of the family
      Nodaviridae. Its genome consists of two positive-sense RNA molecules, RNA1
      (replicase gene) and RNA2 (coat protein gene), which are encapsidated into a
      single virion. Expression of coat protein in Sf21 cells using a baculovirus
      vector results in formation of virus-like particles (VLPs) whose capsids are
      structurally indistinguishable from native virions. However, RNA packaging is not
      specific for RNA2, the coat protein message. Using ribonuclease protection
      assays, we showed that the fraction of RNA2 in VLPs is 19% relative to the amount
      present in a population of native virions. To investigate possible reasons for
      the reduced level of RNA2, we generated two new baculovirus vectors, AcR1delta
      and AcR2delta, expressing the replicase gene and the coat protein gene,
      respectively. The inserted genes carried the self-cleaving hepatitis delta
      ribozyme sequence at the 3' end to allow for synthesis of RNA1 and RNA2
      transcripts with authentic 3' ends. Infection of Sf21 cells with AcR2delta
      yielded VLPs that contained 66% RNA2 relative to native virions. Coinfection of
      Sf21 cells with AcR1delta and AcR2delta launched self-directed FHV replication
      and resulted in formation of particles most of which contained RNA1 and RNA2.
      However, a small fraction of particles containing cellular RNA was detected as
      well. The latter particles could be eliminated by infecting Sf21 cells with
      AcR1delta followed by transfection with in vitro synthesized transcripts of RNA2.
      We have further utilized this system to show that two coat protein deletion
      mutants with distinct RNA packaging defects form mosaic virus capsids but do not
      complement each other to rescue specific packaging of FHV RNAs.

PMID- 12504537
TI  - The M2 gene segment is involved in the capacity of reovirus type 3Abney to induce
      the oily fur syndrome in neonatal mice, a S1 gene segment-associated phenotype.
AB  - Oral inoculation of reovirus type 3 Abney (T3A) into neonatal mice induces
      hepatitis and the biliary atresia-associated oily fur syndrome (OFS), a phenotype
      previously linked to the S1 gene. We found that following oral inoculation, none
      of three T3A mutants, JH2, JH3, and JH4, containing different single amino acid
      substitutions in the M2 gene, induced the OFS or extensive liver necrosis.
      Similarly, reassortant viruses containing both a JH4-S1 and a JH4-M2 gene segment
      did not induce the OFS, whereas another reassortant containing a JH4-S1 gene and
      a M2 gene from reovirus type 3 Dearing fully recovered this capacity. Together,
      these results constitute the first evidence for the involvement of the M2 gene in
      the S1 gene-associated capacity of T3A to induce hepatobiliary disease in
      neonatal mice.

PMID- 12504538
TI  - A shine-dalgarno-like sequence mediates in vitro ribosomal internal entry and
      subsequent scanning for translation initiation of coxsackievirus B3 RNA.
AB  - Translation initiation of coxsackievirus B3 (CVB3) RNA is directed by an internal
      ribosome entry site (IRES) within the 5' untranslated region. However, the
      details of ribosome-template recognition and subsequent translation initiation
      are still poorly understood. In this study, we have provided evidence to support
      the hypothesis that 40S ribosomal subunits bind to CVB3 RNA via basepairing with
      18S rRNA in a manner analogous to that of the Shine-Dalgarno (S-D) sequence in
      prokaryotic systems. We also identified a new site within both the 18S rRNA and
      the polpyrimidine-tract sequence of the IRES that allows them to form stronger
      sequence complementation. All these data were obtained from in vitro translation
      experiments using mutant RNAs containing either an antisense IRES core sequence
      at the original position or site-directed mutations or deletions in the
      polypyrimidine tract of the IRES. The mutations significantly reduced translation
      efficiency but did not abolish protein synthesis, suggesting that the S-D-like
      sequence is essential, but not sufficient for ribosome binding. To determine how
      ribosomes reach the initiation codon after internal entry, we created additional
      mutants: when the authentic initiation codon at nucleotide (nt) 742 was mutated,
      a 180-nt downstream in-frame AUG codon at nt 922 is able to produce a truncated
      smaller protein. When this mutation was introduced into the full-length cDNA of
      CVB3, the derived viruses were still infectious. However, their infectivity was
      much weaker than that of the wild-type CVB3. In addition, when a stable stem-loop
      was inserted upstream of the initiation codon in the bicistronic RNA, translation
      was strongly inhibited. These data suggest that ribosomes reach the initiation
      codon from the IRES likely by scanning along the viral RNA.

PMID- 12504539
TI  - The importance of alfalfa mosaic virus coat protein dimers in the initiation of
      replication.
AB  - Deletion and substitution mutations affecting the oligomerization of alfalfa
      mosaic virus (AMV) coat protein (CP) were studied in protoplasts to determine
      their effect on genome activation, an early step in AMV replication. The CP
      mutants that formed dimers, CPDeltaC9 and CPC-A(R)F, were highly active in
      initiating replication with 63-84% of wild-type (wt) CP activity. However, all
      mutants that did not form dimers, CPDeltaC18, CPDeltaC19, CPC-WFP, and CPC-W,
      were much less active with 19-33% of wt CP activity. The accumulation and
      solubility of mutant CPs expressed from a virus-based vector in Nicotiana
      benthamiana were similar to that of wt CP. Analysis of CP-RNA interactions
      indicated that CP dimers and CP monomers interacted very differently with AMV RNA
      3' ends. These results suggest that CP dimers are more efficient for replication
      than CP monomers because of differences in RNA binding rather than differences in
      expression and accumulation of the mutant CPs in infected cells.

PMID- 12504540
TI  - Systematic search fails to detect immunogenic MHC class-I-restricted determinants
      encoded by influenza A virus noncoding sequences.
AB  - It has been demonstrated in a number of systems that CD8+ T cells (T CD8+) can be
      induced by peptides encoded in alternative reading frames (ARFs) that do not
      appear to code for bona fide proteins. The biological relevance of ARF peptides
      remains to be firmly established, however. With this as a goal, we systematically
      searched for ARF determinants recognized by mouse T CD8+ induced by influenza A
      virus infection. Of 35 candidate ARF peptides that matched H-2 Db, Kb, or Kd
      binding motifs, we found that 13 bind to their respective class I molecules at or
      above the minimal affinity associated with immunogenicity established by past
      studies. Nine of these peptides were able to induce T CD8+ capable of recognizing
      peptide-coated target cells. Of these, only a lone determinant is antigenic and
      immunogenic in the context of influenza A virus infections. Ironically, this
      peptide is derived from a reading frame that encodes a previously unknown
      influenza virus protein. These findings suggest that alternative reading frames
      are not a significant source of antigenic peptides in influenza virus infections
      and raise doubts regarding the general biological significance of ARF
      determinants.

PMID- 12504541
TI  - Characterization of the poliovirus 147S particle: new insights into poliovirus
      uncoating.
AB  - A Sabin 1 strain poliovirus (PV) mutant, S1(2Y-1I), carrying a Tyr at amino acid
      position VP2(142) and an Ile at position VP1(160), can establish persistent
      infections in HEp-2c cells. This mutant forms atypical 147S particles upon
      interaction at 0 degrees C with either cells expressing PV receptor (PVR) CD155,
      or PVR-IgG2a, a chimeric molecule consisting of an extracellular moiety of PVR
      and the hinge and Fc portion of a mouse IgG2a. Upon interaction with PVR at 37
      degrees C, S1(2Y-1I), similar to the parental strain, forms both 135S A particles
      and 80S empty capsids. At 0 degrees C, surprisingly, at a concentration equal to
      or greater than 5 nM, PVR-IgG2a induced both the extrusion of VP4 from the capsid
      of S1(2Y-1I) and the formation of 80S particles. The same transitions were
      observed at 0 degrees C with the parental strain Sabin 1 at 40 nM PVR-IgG2a.
      Thus, the formation of 80S particles and VP4 extrusion, considered as one of the
      steps of PV uncoating, can be temperature-independent at high PVR concentration.
      This implies that structural changes of the PV capsid occurred following
      adsorption at low temperature.

PMID- 12504542
TI  - Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV
      associated dementia.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection often results in disorders
      of the central nervous system, including HIV-associated dementia (HAD). It is
      suspected that tumor necrosis factor-alpha (TNFalpha) released by activated
      and/or infected macrophages/microglia plays a role in the process of neuronal
      damage seen in AIDS patients. In light of earlier studies showing that the
      activation of the insulin-like growth factor I receptor (IGF-IR) exerts a strong
      neuroprotective effect, we investigated the ability of IGF-I to protect neuronal
      cells from HIV-infected macrophages. Our results demonstrate that the conditioned
      medium from HIV-1-infected macrophages, HIV/CM, causes loss of neuronal processes
      in differentiated PC12 and P19 neurons and that these neurodegenerative effects
      are associated with the presence of TNFalpha. Furthermore, we demonstrate that
      IGF-I rescues differentiated neurons from both HIV/CM and TNFalpha-induced damage
      and that IGF-I-mediated neuroprotection is strongly enhanced by overexpression of
      the wt IGF-IR cDNA and attenuated by the antisense IGF-IR cDNA. Finally, IGF-I
      mediated antiapoptotic pathways are continuously functional in differentiated
      neurons exposed to HIV/CM and are likely supported by TNFalpha-mediated
      phosphorylation of I(kappa)B. All together these results suggest that the balance
      between TNFalpha and IGF-IR signaling pathways may control the extent of neuronal
      injury in this HIV-related experimental setting.

PMID- 12504543
TI  - Antibody fragments selected by phage display against the nuclear localization
      signal of the HIV-1 Vpr protein inhibit nuclear import in permeabilized and
      intact cultured cells.
AB  - The HIV-1 Vpr protein harbors a nuclear localization signal in its N-terminal
      domain. A peptide bearing this domain and which is designated VprN has been used
      as a target to screen a phage display single chain Fv (scFv) library. Here we
      report the isolation of anti-VprN scFv fragments from this library. The purified
      scFv fragments were able to bind the VprN peptide in an ELISA-based system and to
      inhibit VprN-mediated nuclear import in permeabilized as well as in intact
      microinjected cells. Furthermore, the anti-VprN scFv fragments recognized the
      full-length recombinant Vpr protein and inhibited its nuclear import. The same
      scFv fragments did not inhibit nuclear import mediated by the nuclear
      localization signal of the SV40 large T-antigen demonstrating a specific effect.
      The use of the described inhibitory anti-VprN scFv fragments to study nuclear
      import of viral karyophilic proteins and their therapeutic potential is
      discussed.

PMID- 12504544
TI  - Rotavirus-specific B cells induced by recent infection in adults and children
      predominantly express the intestinal homing receptor alpha4beta7.
AB  - In vivo replication of rotaviruses is generally limited to enterocytes. Because
      of this restriction, most blood circulating rotavirus-specific B cells are
      hypothesized to originate in Peyer's patches and should express the intestinal
      homing receptor alpha4beta7. To test this hypothesis in humans, we used a flow
      cytometry assay that identifies antigen-activated (IgD-) B cells (CD19+) that
      express surface rotavirus-specific immunoglobulin. With this assay we could
      detect rotavirus-specific B cells in both children and adults with an acute
      rotavirus (RV) infection. Staining with an anti-alpha4beta7 monoclonal antibody,
      we could determine that B cells that express rotavirus-specific surface
      immunoglobulin predominantly express alpha4beta7. The response of rotavirus
      specific antibody-secreting cells in the peripheral blood of children and adults
      with acute rotavirus infection was also studied by ELISPOT. The antibody
      secreting cells of children were mainly of the IgM isotype, while the antibody
      secreting cells of adults were predominantly of the IgA and IgG isotype.
      alpha4beta7+ and alpha4beta7- subsets of peripheral blood mononuclear cells were
      purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus
      specific antibody-secreting cells were predominantly present in the alpha4beta7+
      subpopulation. The flow cytometry assay we have described will permit future
      studies to characterize the phenotype of virus-specific B cells and could be
      useful in the study of the immunogenicity and protective efficacy of RV vaccines
      and the identification of markers of protective immunity.

PMID- 12504545
TI  - Displaying epidermal growth factor on spleen necrosis virus-derived targeting
      vectors.
AB  - Targeted gene transfer into human cells has previously been achieved with spleen
      necrosis virus (SNV)-derived vector particles harboring envelope (Env) proteins
      which carry single chain Fv (scFv) domains derived from antibodies. Such cell
      targeting vectors have been found to directly transduce human cells expressing
      the cell surface molecules recognized by the respective scFv. In an attempt to
      achieve targeted gene transfer into epidermal growth factor receptor (EGFR)
      positive human cells, SNV vector particles carrying a surface (SU) envelope
      protein N-terminally modified with the EGF domain and the wildtype transmembrane
      protein were generated. However, direct transduction of EGFR-positive cells was
      not detected. Canine D17 cells, which can be infected by wildtype SNV, were also
      not transduced. Infectivity of D17 cells was restored by removal of the EGF
      modification via cleavage of a factor Xa site located between the EGF domain and
      the SU protein or by blocking the EGFRs on the cell surface by EGF treatment. The
      properties of SNV-EGF vector particles as described here are similar to those of
      murine leukemia virus-derived vector particles harboring envelope proteins
      modified with a growth factor-derived domain. It seems therefore that, although
      scFv-modified SNV allows direct cell targeting, EGF-modified SNV allows only
      indirect cell targeting.

PMID- 12504546
TI  - DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of
      macrophages and endothelial cells.
AB  - Ebola virus exhibits a broad cellular tropism in vitro. In humans and animal
      models, virus is found in most tissues and organs during the latter stages of
      infection. In contrast, a more restricted cell and tissue tropism is exhibited
      early in infection where macrophages, liver, lymph node, and spleen are major
      initial targets. This indicates that cellular factors other than the broadly
      expressed virus receptor(s) modulate Ebola virus tropism. Here we demonstrate
      that the C-type lectins DC-SIGN and DC-SIGNR avidly bind Ebola glycoproteins and
      greatly enhance transduction of primary cells by Ebola virus pseudotypes and
      infection by replication-competent Ebola virus. DC-SIGN and DC-SIGNR are
      expressed in several early targets for Ebola virus infection, including dendritic
      cells, alveolar macrophages, and sinusoidal endothelial cells in the liver and
      lymph node. While DC-SIGN and DC-SIGNR do not directly mediate Ebola virus entry,
      their pattern of expression in vivo and their ability to efficiently capture
      virus and to enhance infection indicate that these attachment factors can play an
      important role in Ebola transmission, tissue tropism, and pathogenesis.

PMID- 12504547
TI  - Immunogenicity and ability of variable loop-deleted human immunodeficiency virus
      type 1 envelope glycoproteins to elicit neutralizing antibodies.
AB  - It has been extremely difficult to elicit broadly cross-reactive neutralizing
      antibodies (Nabs) against human immunodeficiency virus type 1 (HIV-1). In this
      study, we compared the immunogenic properties of the wild-type and variable loop
      deleted HIV-1 envelope glycoproteins. Mice were immunized with recombinant
      vaccinia viruses expressing either the wild-type or the variable loop-deleted (V1
      2, V3, V4, and V1-3) HIV-1(DH12) gp160s. The animals were subsequently boosted
      with respective recombinant gp120s. All envelope constructs elicited similar
      levels of gp120-binding antibodies when analyzed by enzyme-linked immunosorbent
      assay (ELISA). However, the highest neutralizing activity was observed in sera
      from animals immunized with the wild-type envelope protein, followed by those
      immunized with DeltaV4 and DeltaV1-2. No neutralizing activity was detected in
      sera from animals immunized with DeltaV3 or DeltaV1-3. To identify immunogenic
      epitopes, ELISA was performed with overlapping 15-mer peptides that cover the
      entire length of gp120. For the wild-type gp120, the immunogenic epitopes mapped
      primarily to the variable loops V1-2 and to the conserved regions C1 and C5. When
      they were plotted onto known coordinates of gp120 core crystal structure, the
      epitopes in the conserved regions mapped predominantly to the inner domain of the
      protein. By immunizing with variable loop-deleted envelopes, the immune responses
      could be redirected to other regions of the protein. However, the newly targeted
      epitopes were neither on the exposed surface of the protein nor on the receptor
      binding regions. Interestingly, the removal of the V3 loop resulted in loss of
      immunoreactivity for both V3 and V1/V2 loops, suggesting structural interaction
      between the two regions. Our results suggest that obtaining broadly reactive Nabs
      may not be achieved simply by deleting the variable loops of gp120. However, the
      observation that the immune responses could be redirected by altering the protein
      composition might allow us to explore alternative strategies for modifying the
      antigenic properties of HIV-1 envelope glycoprotein.

PMID- 12504548
TI  - Influenza A virus hemagglutinin containing basolateral localization signal does
      not alter the apical budding of a recombinant influenza A virus in polarized MDCK
      cells.
AB  - Morphogenesis of influenza virus is a complex multistep process involving
      transport of all viral components as either individual or subviral components to
      the specified assembly site and interaction among the viral components in an
      ordered fashion to initiate the budding process. Envelope glycoprotein(s) is
      believed to be the major determinant in selecting the viral budding site since
      the majority of the viral glycoproteins are directed to the budding site
      independent of other viral components. Influenza viruses bud from the apical
      surface of polarized epithelial cells and all three envelope proteins,
      hemagglutinin (HA), neuraminidase (NA), and M2, are also targeted independently
      to the apical surface. Since HA is the major viral envelope protein, we decided
      to test whether basolaterally expressed HA can make the virus bud from the
      basolateral surface. Accordingly, we introduced the tyrosine-based basolateral
      sorting signal to the cytoplasmic tail of HA by changing Cys561 --> Tyr561 and
      generated a transfectant virus by reverse genetics. Compared to the parent WSN
      virus, the mutant virus (HAtyr virus) contained less HA on its envelope. While
      the wild-type (wt) HA was >95% apical, the mutated HA (HAtyr) was approximately
      60% basolateral in both transfected and virus-infected polarized MDCK cells.
      Also, HAtyr protein exhibited a much higher rate of endocytosis than the wt HA,
      in both apical and basolateral surface of transfected as well as virus-infected
      cells. However, the HAtyr virus, similar to wt WSN virus, was seen to bud almost
      exclusively (>99%) from the apical side of polarized MDCK cells. This finding was
      confirmed by using neuraminidase to facilitate virus release, by treating the
      collected virus particles with trypsin to cleave HA0 --> HA1 and HA2, by protein
      analysis of released virus particles, and finally, by electron microscopy.
      Therefore HA, the major glycoprotein alone, does not determine the budding site,
      and other factor(s), possibly both viral and host, is responsible for selecting
      the budding site of influenza virus.

PMID- 12504549
TI  - Mutation of the protein tyrosine kinase consensus site in the herpes simplex
      virus 1 alpha22 gene alters ICP22 posttranslational modification.
AB  - We previously reported that at least eight HSV-1 and five HSV-2 proteins were
      tyrosine phosphorylated in infected human and mouse cells and the first
      phosphotyrosine-modified gene product identified was the ICP22 regulatory protein
      (Blaho, J. A., Zong, C. S., and Mortimer, K. A., 1997, J. Virol. 71, 9828-9832).
      All electrophoretic forms of ICP22 are tyrosine phosphorylated with the exception
      of the fastest migrating (unmodified) isoform. We now report the following. (i)
      ICP22 that reacted with a specific anti-phosphotyrosine antibody contained a
      significant amount of phosphotyrosine based on phospho-amino acid analysis. These
      results validate the discovery of ICP22 tyrosine phosphorylation. (ii) Wild-type
      ICP22 extracted from infected HEp-2 cells migrated as at least seven isoforms,
      termed ICP22a-g, in denaturing gels. (iii) The primary structure of ICP22
      possesses a sequence that is homologous to protein tyrosine kinase recognition
      sites. A virus, termed RF141, was generated in which ICP22 tyrosine(193) in the
      kinase target site was mutated to an alanine. (iv) Biochemical analyses of
      infected HEp-2 and primary HFF cells indicated that the distributions of ICP22
      isoforms differed between RF141 and control HSV-1(F). (v) The accumulations of
      representative viral polypeptides in RF141-infected HEp-2 cells appeared similar
      to wild-type virus. (vi) RF141 had reduced efficiencies of plating in HFF cells
      compared to control Vero cells. These differences increased as the multiplicity
      of infection decreased. Based on these results, we conclude (vii) that ICP22
      tyrosine(193) is required for optimal posttranslational modification of the
      protein in HSV-1 infected human epithelial HEp-2 and primary human fibroblast
      cells.

PMID- 12504550
TI  - Transcriptional analysis of porcine circovirus type 2.
AB  - Porcine circovirus type 2 (PCV2) is the causative agent of an emerging swine
      disease, postweaning multisystemic wasting syndrome. In this work, the RNAs of
      PCV2 synthesized during productive infection in porcine kidney cells were
      characterized. A total of nine RNAs were detected. They include the viral capsid
      protein RNA (CR), a cluster of five Rep-associated RNAs (designated Rep, Rep',
      Rep3a, Rep3b, and Rep3c), and three NS-associated RNA (designated NS515, NS672,
      and NS0). Members of the Rep-associated RNA cluster all share common 5' and 3'
      nucleotide sequences and they also share 200 common 3' nucleotides with the NS
      associated RNAs. Rep, capable of coding for the replication-associated-protein
      (RepP), appears to be the primary transcript that gives rise to Rep', Rep3a,
      Rep3b, and Rep3c by alternate splicing. Protein sequence alignment showed that
      RepP and the Rep' protein of PCV2 are equivalent to those described for PCV type
      1 (PCV1) (a nonpathogenic virus), which had been shown to be essential for viral
      DNA replication. The results also suggest that NS515, NS672, and NS0 are
      transcribed from three different promoters inside ORF1 downstream of the Rep
      promoter. To date, only three RNAs (CR, Rep, and Rep') have been reported for
      PCV1-infected porcine kidney cells. Therefore, it is important to apply similar
      strategies from this study to reexamine the transcription pattern of PCV1.

PMID- 12504551
TI  - Ability of small animal cells to support the postintegration phase of human
      immunodeficiency virus type-1 replication.
AB  - We examine the potential for a broad range of small animal cells, including
      rodent, mink, and avian cells, from multiple tissues to support postintegration
      steps of HIV-1 replication. These cells were engineered so as to support a stable
      expression of human cyclin T1 and were further transduced with HIV-1 gag and pol
      genes. Viral gene expression was activated by the presence of human cyclin T1,
      but, with the exception of mink cells, was not at the level seen in human cells.
      Furthermore, there were considerable defects in p24 CA release, in particular in
      the case of rodent cells. Fractionation of Gag proteins by sucrose floatation
      revealed that the Gag in human cells trafficked to membrane fractions and was
      processed to p24 CA and p17 MA efficiently. Confocal imaging demonstrated that
      Gag was localized in a punctate pattern at the plasma membrane as well as
      intracellular membrane trans-Golgi cisternae in these cells. In contrast, the
      majority of Gag in rodent cells was largely present in cytosolic complexes and
      remained unprocessed. Labeling with [9,10(n)-(3)H]myristic acid showed a similar
      degree of N-myristoylated Pr55(gag) in rodent and human cells, indicating that
      while N-myristoylation of Gag was essential for membrane binding, it was not
      sufficient to confer membrane targeting specificity. Remarkably, despite the
      reduced level of intracellular Gag processing, mink Mv.1.Lu cells did not appear
      to differ significantly from human cells in support of virion assembly and
      release. Analysis of reciprocal heterokaryons suggested that the cellular
      factor(s) required for efficient assembly and release of infectious virions is
      lacking in murine cells but appears to be functionally present in mink as well as
      human cells. Our findings confirm and extend previous reports of multiple blocks
      to HIV replication in nonhuman cells that are most profound in murine cells. They
      also raise the possibility that other small animals, such as mink, could serve as
      novel model systems for studying HIV-1 infection and disease.

PMID- 12504552
TI  - Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine
      candidate generated by plasmid-based reverse genetics.
AB  - Avian influenza A H5N1 viruses similar to those that infected humans in Hong Kong
      in 1997 continue to circulate in waterfowl and have reemerged in poultry in the
      region, raising concerns that these viruses could reappear in humans. The
      currently licensed trivalent inactivated influenza vaccines contain hemagglutinin
      (HA) and neuraminidase genes from epidemic strains in a background of internal
      genes derived from the vaccine donor strain, A/Puerto Rico/8/34 (PR8). Such
      reassortant candidate vaccine viruses are currently not licensed for the
      prevention of human infections by H5N1 influenza viruses. A transfectant H5N1/PR8
      virus was generated by plasmid-based reverse genetics. The removal of the
      multibasic amino acid motif in the HA gene associated with high pathogenicity in
      chickens, and the new genotype of the H5N1/PR8 transfectant virus, attenuated the
      virus for chickens and mice without altering the antigenicity of the HA. A
      Formalin-inactivated vaccine prepared from this virus was immunogenic and
      protected mice from subsequent wild-type H5N1 virus challenge. This is the first
      successful attempt to develop an H5N1 vaccine seed virus resembling those used in
      currently licensed influenza A vaccines with properties that make it a promising
      candidate for further evaluation in humans.

PMID- 12504553
TI  - Binding characteristics determine the neutralizing potential of antibody
      fragments specific for antigenic domain 2 on glycoprotein B of human
      cytomegalovirus.
AB  - Site I of antigenic domain 2 (AD-2) on human cytomegalovirus glycoprotein B (gB)
      is poorly immunogenic in both man and mouse and knowledge about antibody
      repertoires reactive with this epitope is thus limited. Here we have
      characterized a phage display-derived repertoire of antibody fragments specific
      for this epitope in terms of antigen recognition, fine-specificity, and virus
      neutralizing capacity. Our results show that the functional properties within a
      closely related repertoire may differ widely and that the effectiveness of the
      members of the repertoire to neutralize the virus is determined by the fine
      specificity and kinetics of the interaction with the antigen. The half-life of
      the interaction between monomeric antibody fragments and gB seems to be
      particularly critical for the neutralizing capacity. We also demonstrate that
      sequence variation within gB allows virus variants to escape at least a part of
      the AD-2-specific neutralizing antibody repertoire, apparently without preventing
      antibody binding to the epitope.

PMID- 12504554
TI  - Emergence of cytotoxic T lymphocyte escape mutants following antiretroviral
      treatment suspension in rhesus macaques infected with SIVmac251.
AB  - Structured treatment interruption (STI) of antiretroviral drugs has been proposed
      as an alternative approach for managing patients infected with HIV-1. While STI
      is thought to spare drug-related side effects and enhance the HIV-1-specific
      immune response, the long-lasting clinical benefit of this approach remains
      uncertain, particularly in patients with long-standing HIV-1 infection. Here, we
      investigated the basis of unabated virological replication following different
      STI regimens in rhesus macaques that expressed the MHC class I Mamu-A*01 molecule
      treated during acute and long-standing infection with SIVmac251. An amino acid
      change at the anchor residue within the immunodominant Mamu-A*01-restricted
      Gag(181-189) CM9 epitope (T --> A) in one of six macaques with acute SIVmac251
      infection and in three of four macaques with long-standing SIVmac251 infection (T
      --> A; T --> S; S --> C) was found in the majority of plasma virus. These amino
      acid changes have been shown to severely decrease binding of the corresponding
      peptides to the Mamu-A*01 molecule and, in the case of the T --> A change, escape
      from CTL. In one macaque with long-standing SIVmac251 infection, a mutation
      emerged that conferred resistance to one of the antiretroviral drugs (PMPA) as
      well. These results provide insights into the mechanism underlying the limited
      capacity of repeated interruption of antiretroviral therapy as an approach to
      restrain viral replication. In addition, these data also suggest that
      interruption of therapy may be less effective in chronic infection because of
      preexisting immune escape and that immune escape is a risk of interruption of
      therapy.

PMID- 12504555
TI  - Time course of Gag protein assembly in HIV-1-infected cells: a study by
      immunoelectron microscopy.
AB  - Recent biochemical studies have identified high molecular complexes of the HIV
      Gag precursor in the cytosol of infected cells. Using immunoelectron microscopy
      we studied the time course of the synthesis and assembly of a HIV Gag precursor
      protein (pr55gag) in Sf9 cells infected with recombinant baculovirus expressing
      the HIV gag gene. We also immunolabeled for pr55gag human T4 cells acutely or
      chronically infected with HIV-1. In Sf9 cells, the time course study showed that
      the first Gag protein appeared in the cytoplasm at 28-30 h p.i. and that budding
      started 6-8 h later. Colloidal gold particles, used to visualize the Gag protein,
      were first scattered randomly throughout the cytoplasm, but soon clusters
      representing 100 to 1000 copies of pr55gag were also observed. By contrast, in
      cells with budding or released virus-like particles the cytoplasm was virtually
      free of gold particles while the released virus-like particles were heavily
      labeled. Statistical analysis showed that between 80 and 90% of the gold
      particles in the cytoplasm were seen as singles, as doublets, or in small groups
      of up to five particles probably representing small oligomers. Clusters of gold
      particles were also observed in acutely infected lymphocytes as well as in
      multinuclear cells of chronically infected cultures of T4 cells. In a few cases
      small aggregates of gold particles were found in the nuclei of T4 lymphocytes.
      These observations suggest that the Gag polyprotein forms small oligomers in the
      cytoplasm of expressing cells but that assembly into multimeric complexes takes
      place predominantly at the plasma membrane. Large accumulations of Gag protein in
      the cytoplasm may represent misfolded molecules destined for degradation.

PMID- 12504556
TI  - The premature termination model: a possible third mechanism for subgenomic mRNA
      transcription in (+)-strand RNA viruses.

PMID- 12504557
TI  - A new packaging cell line for SV40 vectors that eliminates the generation of T
      antigen-positive, replication-competent recombinants.
AB  - Simian virus 40 (SV40) vectors are efficient vehicles for gene delivery to
      hematopoietic and hepatic cells. To ensure their replication incompetence and
      because of safety considerations, it is critical that the vectors do not contain
      T-antigen sequences. Available packaging cell lines for T-antigen replacement
      vectors, COS and CMT4, contain considerable sequence identity with the vectors,
      leading to homologous recombination and reacquisition of the T-antigen gene. We
      constructed a packaging cell line, COT18, with minimal sequence identity to the
      vector. Vector stocks produced by passaging on COT18 had high transducing
      activity and undetectable levels of T-antigen-positive, replication-competent
      contaminants. This cell line provides a means for the preparation of safe SV40
      vector stocks.

PMID- 12504558
TI  - Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes
      from cellular components.
AB  - Signal transducer and activator of transcription (STAT) proteins are normally
      long-lived, but infection with certain Paramyxoviruses results in efficient loss
      of IFN-responsive STAT1 or STAT2. Expression of a virus-encoded protein called
      "V" is sufficient to mediate the destruction of STAT proteins. STAT degradation
      is blocked by proteasome inhibitors, strongly implicating the ubiquitin (Ub)
      proteasome targeting system. We demonstrate that cellular expression of V
      proteins from simian virus 5 (SV5) and type II human parainfluenza virus (HPIV2)
      induces polyubiquitylation of STAT1 and STAT2 targets. In vitro, the V proteins
      catalyze Ub transfer in an ATP-dependent process that requires both Ub-activating
      (E1) and Ub-conjugating (E2) activities. Furthermore, SV5 and HPIV2 V-interacting
      protein partners were isolated by affinity purification from human cells and
      reveal a complex of associated cellular proteins. This complex includes both
      STAT1 and STAT2, and the damaged DNA binding protein, DDB1. In addition, a
      protein related to a family of cellular Ub ligase complex subunits, cullin 4A
      (Cul4A), associated with the V proteins. The roles of both DDB1 and Cul4A in
      STAT1 degradation by SV5 infection were analyzed using small interfering RNAs.
      These findings demonstrate the assembly of a V-dependent degradation complex that
      includes STAT1, STAT2, DDB1, and Cul4A. In agreement with prior nomenclature on
      SCF-type cellular E3 enzymes, we refer to this complex as VDC.

PMID- 12504559
TI  - The domain order of mammalian capping enzyme can be inverted and baculovirus
      phosphatase can function in cap formation in vivo.
AB  - The bifunctional mammalian mRNA capping enzyme (Mce1) consists of an N-terminal
      triphosphatase domain Mce1(1-210) fused to a C-terminal guanylyltransferase
      domain Mce1(211-597). The physical domain order H(2)N-triphosphatase
      guanylyltransferase-COOH mimics the temporal order of the capping reactions. To
      determine if the physical domain order is functionally important in vivo, we
      engineered an "inverted" mammalian capping enzyme InvMce1 [H(2)N-Mce1(211-597)-(1
      210)-COOH]. We found that InvMce1 complemented the growth of Saccharomyces
      cerevisiae cet1delta and ceg1delta strains in which the endogenous yeast
      triphosphatase and guanylyltransferase genes were deleted. By testing truncated
      versions of InvMce1, we determined that Mce1(1-178) comprises a minimal
      functional triphosphatase domain. Baculovirus phosphatase (BVP) is a
      monofunctional single-domain protein with RNA triphosphatase and RNA
      diphosphatase activities and an undefined role in viral RNA metabolism. Here we
      demonstrated that BVP can function as an RNA triphosphatase for cap formation in
      vivo when fused to the C-terminus of Mce1(211-597). By characterizing a series of
      InvMce1-BVP derivatives with amino acid substitutions in the phosphate-binding
      loop of BVP, we showed that the in vivo activity of the mutant chimeras in cap
      formation is contingent upon in vitro phosphohydrolase activity of the respective
      BVP proteins. BVP catalysis in vitro was not limited to 5'-phosphorylated RNA or
      nucleotide substrates, but also embraced tripolyphosphatase and pyrophosphatase
      activities. BVP-specific activities with nucleotide and inorganic substrates were
      as follows: ATP (14 min(-1)), ADP (31 min(-1)), PPP(i) (3.7 min(-1)), and PP(i)
      (1 min(-1)). BVP did not hydrolyze AMP. We surmise that BVP has adapted the
      cysteinyl phosphatase fold to the hydrolysis of phosphoanhydrides.

PMID- 12504560
TI  - The requirement of varicella zoster virus glycoprotein E (gE) for viral
      replication and effects of glycoprotein I on gE in melanoma cells.
AB  - The glycoprotein E (gE) of varicella zoster virus (VZV), encoded by ORF68, is the
      most abundant viral glycoprotein. In the current experiments, we demonstrated
      that ORF68 deletion was incompatible with recovery of infectious virus from VZV
      cosmids. Replacing ORF68 at a nonnative AvrII site in the genome restored
      infectivity. Further, we found that VZV gE could be expressed under the control
      of the Tet-On promoter in stably transfected melanoma cell lines (Met-gE cells)
      without evidence of toxicity. In these Met-gE cells, gE colocalized with gamma
      adaptin, a trans Golgi network marker, in perinuclear sites, but did not reach
      plasma membranes. In order to investigate how infection altered gE localization,
      we made a recombinant virus, vOka-MSPgE, with ORF68 from the VZV MSP strain. VZV
      MSP encodes a mutant gE protein (D150N) that lacks the mAb epitope, 3B3 (Santos
      et al., Virology 275, 306-317, 2000), whereas Met-gE protein binds mAb 3B3.
      Within 48 h after Met-gE cells were infected with vOka-MSPgE, the steady-state
      distribution of Met-gE protein extended beyond the perinuclear areas to other
      cytoplasmic sites and to plasma membranes. A second recombinant, vOka-MSPgE
      without gI (vOka-MSPgEdeltagI), was constructed to investigate Met-gE protein
      distribution in the absence of gI. The redistribution of Met-gE protein which was
      observed by 48 h after vOka-MSPgE infection did not occur until 5 days (140 h)
      within vOka-MSPgEdeltagI infected cells. After vOka-MSPgE infection of Met-gE
      cells, most Met-gE protein was in the final 94K mature form by 72 h. However,
      progression to predominance of mature gE was delayed in Met-gE cells infected
      with vOka-MSPgEdeltagI. These observations confirm our hypothesis that VZV gE is
      essential, based upon the demonstration of restored infectivity after replacing
      ORF68 in a nonnative site in the genome, and provide further evidence of the role
      of gI in facilitating the maturation and intracellular distribution of this
      critical VZV glycoprotein.

PMID- 12504561
TI  - Expression of human CD81 in transgenic mice does not confer susceptibility to
      hepatitis C virus infection.
AB  - We previously demonstrated that hepatitis C virus (HCV) binds to human CD81
      through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in
      transgenic mice was expected to provide a new tool to study HCV infection in
      vivo, as the chimpanzee is the only species currently available as a laboratory
      animal model that can be infected with HCV. We produced transgenic mice
      expressing the human CD81 protein in a wide variety of tissues. We confirmed
      binding of recombinant E2 glycoprotein to the liver tissue as well as to
      thymocytes and splenic lymphocytes in the transgenic mice. We inoculated
      chimpanzee plasma infected with HCV into these animals. None of these transgenic
      animals showed evidence of viral replication. Furthermore, human CD81 transgenic
      mice that lack expression of endogenous mouse CD81 were also resistant to HCV
      infection. We conclude that expression of human CD81 alone is insufficient to
      confer susceptibility to HCV infection in the mouse. The presence of additional
      possible factors for HCV infection is discussed.

PMID- 12504562
TI  - Subgenomic hepatitis C virus replicons inducing expression of a secreted
      enzymatic reporter protein.
AB  - We constructed dicistronic, subgenomic hepatitis C virus (HCV) replicons in which
      the sequence encoding the human immunodeficiency virus (HIV) tat protein was
      placed in the upstream cistron, between the HCV 5'NTR and a picornaviral 2A
      proteinase sequence fused to the selectable marker Neo. Stably transformed Huh7
      cells expressing secreted alkaline phosphatase (SEAP) under transcriptional
      control of the HIV LTR promoter actively secreted SEAP following transfection
      with these replicon RNAs. Extracellular SEAP activity correlated closely with
      intracellular HCV RNA levels, as determined by Northern blotting and real-time RT
      PCR analysis. These RNAs replicated efficiently despite the absence of core
      protein-coding sequence downstream of the HCV IRES. The replication efficiency of
      replicons derived from the HCV-N strain of HCV was significantly greater than
      those derived from Con1 in transiently transfected cells. Using this reporter
      system, we have demonstrated significant differences in the response to
      interferon alpha-2b in cell lines containing replicons derived from these two
      strains of HCV.

PMID- 12504563
TI  - Mycophenolic acid inhibits dengue virus infection by preventing replication of
      viral RNA.
AB  - Dengue fever is a mosquito-borne viral disease of global importance with no
      available antiviral therapy. We assessed the ability of mycophenolic acid (MPA),
      a drug currently used as an immunosuppressive agent, to inhibit dengue virus (DV)
      antigen expression, RNA replication, and virus production. Pharmacological
      concentrations of MPA effectively blocked DV infection, decreasing the percentage
      of infected cells by 99% and the levels of secreted virus by up to a millionfold.
      Results were reproduced with four hepatoma cell lines and different flaviviruses,
      including a recent West Nile virus isolate. Experiments were performed to define
      the stage in the viral lifecycle at which MPA abrogates infection. Early steps in
      viral infection, such as viral entry and nucleocapsid uncoating, were not the
      primary targets of MPA action since its inhibitory effect was retained when naked
      DV RNA was transfected directly into cells. Biosynthetic labeling experiments
      showed that MPA did not block the initial phase of viral translation but did
      interfere with viral protein synthesis in the amplification phase. Quantitative
      RT-PCR demonstrated that MPA prevented the accumulation of viral positive- and
      negative-strand RNA as the infection proceeded. We conclude that MPA inhibits
      flavivirus infection by preventing synthesis and accumulation of viral RNA.

PMID- 12504564
TI  - Ethanol strongly potentiates apoptosis induced by HIV-1 proteins in primary human
      brain microvascular endothelial cells.
AB  - Ethanol may have significant effects on human immunodeficiency virus type I (HIV
      1) pathogenesis in vivo. As such, the effects of ethanol treatment were studied
      on the proapoptotic potential of various HIV-1 proteins in primary isolated human
      brain microvascular endothelial cells (MVECs), a major cellular component of the
      blood-brain barrier. Low-passage primary brain MVECs were treated with
      recombinant HIV-1 proteins Nef, Vpr, Tat and gp120 proteins from X4, R5, and X4R5
      viral strains, with and without ethanol at various relevant concentrations. The
      apoptotic potential of each HIV-1 protein with and without ethanol was compared
      with cells treated with ethanol alone or GST protein as a control, under similar
      conditions. Specific HIV-1 proteins induced apoptosis in primary isolated human
      brain MVECs, which was potentiated on treatment with 0.1 and 0.3% (v/v) ethanol.
      Cotreatment with ethanol and specific HIV-1 proteins showed enhanced lactate
      dehydrogenase release, compared with MVECs treated with ethanol alone. The
      presence of ethanol in in vitro culture medium also enhanced HIV-1 protein
      mediated tumor necrosis factor-alpha production, compared with cells treated with
      ethanol alone or GST protein. Thus, these studies demonstrate ethanol's potential
      for inducing apoptosis of human MVECs with relevant HIV-1-specific proteins and
      suggest a potential synergistic effect in augmenting HIV-1 neuroinvasion and
      neuropathogenesis in vivo.

PMID- 12504565
TI  - Intragenic complementation and oligomerization of the L subunit of the sendai
      virus RNA polymerase.
AB  - The RNA-dependent RNA polymerase of Sendai virus consists of two subunits, the L
      and P proteins, where L is thought to be responsible for all the catalytic
      activities necessary for viral RNA synthesis. Sequence alignment of the L
      proteins of a variety of negative-stranded RNA viruses revealed six regions of
      good conservation, designated domains I-VI, which are thought to correspond to
      functional domains of the protein. Analysis of a number of site-directed mutants
      within the six domains of L allowed us to conclude that the activities of the
      polymerase are not simply compartmentalized and that each domain contributes to
      multiple steps in viral RNA synthesis. Nevertheless these domains can function in
      trans since we demonstrate here that intragenic complementation between pairs of
      coexpressed inactive L mutants can restore viral RNA synthesis on an added
      template. Although intragenic complementation is typically very inefficient,
      complementation to restore leader RNA synthesis was surprisingly very efficient
      for some pairs and complementation of mRNA synthesis and genome replication was
      less, but still significant. Complementation occurred with L mutants in five of
      the six domains, the exception being a domain III mutant, and required the
      cotranslation of the two L mutants. C-terminal truncations deleting up to half of
      L were capable of restoring transcription of an inactive domain I L mutant at
      amino acid 379. Oligomerization of L in the polymerase complex was demonstrated
      directly by the co-immunoprecipitation of differentially epitope-tagged full
      length and truncated L proteins. These data are consistent with L protein being
      an oligomer with multiple independent domains each of which exhibits several
      functions.

PMID- 12504566
TI  - Comprehensive analyses of a unique HIV-1-infected nonprogressor reveal a complex
      association of immunobiological mechanisms in the context of replication
      incompetent infection.
AB  - We recently demonstrated that a unique HIV-1-infected nonprogressor was infected
      with a nonevolving replication-incompetent HIV-1 strain, showing a total absence
      of viral evolution in vivo. Potent immune responses against HIV-1 were observed
      in his PBMC, despite an apparent lack of viral replication for at least 8 years.
      His PBMC resisted superinfection with CCR5, CXCR4, and dual-tropic HIV-1 strains,
      although highly purified CD4+ T cells supported infection, but without any
      visible cytopathic effect. Potent noncytolytic CD8+ T cell antiviral activity was
      shown to protect his PBMC from productive infection. This activity was not
      mediated by several known chemokines or IFN-gamma, which were produced at high
      levels after PHA activation of his CD8+ T cells, indicating the action of other
      CAF-like CD8 factors. This antiviral activity was a memory response, induced by
      HIV-specific stimulation to similar levels observed by PHA stimulation, but
      absent in ex vivo resting T cells. Immunological mechanisms associated with this
      antiviral suppressive activity included vigorous Gag-specific helper T cell
      proliferative responses and high-level IFN-gamma release by both CD4 and CD8 T
      cells. These responses were broadly directed against multiple Gag epitopes, both
      previously reported and some novel epitopes. Strong HIV-specific helper T cell
      function was also associated with strong neutralizing antibodies. Understanding
      how to induce these protective immune responses in other individuals could
      provide a major step forward in the design of effective immunotherapies or
      vaccines against HIV infection.

PMID- 12504567
TI  - Growth arrest of HPV-positive cells after histone deacetylase inhibition is
      independent of E6/E7 oncogene expression.
AB  - Inhibitors of histone deacetylase (HDAC) are capable of arresting growth in
      cervical carcinoma cells in the G1 phase of the cell cycle. Although HPV E6/E7
      mRNA steady-state levels appeared to be constant after prolonged treatment, time
      course experiments revealed that viral transcription was transiently down
      regulated between 7-10 h prior to cdk2 suppression. To test whether transitory
      suppression was a prerequisite for the biological outcome after HDAC inhibition,
      we took advantage of two immortalized human keratinocyte cell lines in which
      E6/E7 oncogene expression was controlled by different regulatory regions. After
      treatment with sodium butyrate (NaB) or trichostatin A (TSA), HPV16 upstream
      regulatory region (URR)-directed transcription was down-regulated, showing
      kinetics similar to those in cervical carcinoma cells. In contrast, beta-actin
      promoter controlled E6/E7 transcription was even temporarily increased and
      finally declined to levels initially detected in the untreated controls. Both
      cell lines, however, were arrested in G1 and showed complete suppression of cdk2
      activity that was preceded by a strong up-regulation of the cdk2 inhibitors
      p21(CIP1) and p27(KIP1). These results demonstrate that growth of HPV16/18
      positive cells can be arrested by HDAC inhibitors despite ongoing HPV
      transcription and thus independently of any potential position effects uncoupling
      URR-directed gene expression by adjacent cellular promoters or by downstream 3'
      polyadenylation sites after viral integration into the host genome during
      multistep carcinogenesis.

PMID- 12504568
TI  - High genetic divergence and recombination in Arenaviruses from the Americas.
AB  - The rodent-borne Arenaviruses are divided into two major antigenic groups: the
      Old World and New World complexes. Of the 15 known New World arenaviruses, four
      (Junin, Machupo, Sabia, and Guanarito) have been associated with hemorrhagic
      fever in humans. It has been difficult to assess the pathogenic or epidemic
      potential of the remaining viruses and the threat of emerging disease. We
      obtained full-length small (S) segment sequence data, encoding the nucleoprotein
      (NP) and glycoprotein precursor (GPC), from all American arenaviruses to predict
      their evolutionary and functional relationships. Phylogenetic analysis of NP or
      GPC amino acid sequences from all New World arenaviruses revealed three lineages
      and that Tamiami and Whitewater Arroyo viruses were probably derived from a
      single recombinant progenitor. The results imply that arenaviruses have been
      evolving independently for a very long time, leading to very diverse groupings
      that do not correlate with geography, rodent host, or human epidemic potential.

PMID- 12504569
TI  - Ribonucleotide reductase of shrimp white spot syndrome virus (WSSV): expression
      and enzymatic activity in a baculovirus/insect cell system and WSSV-infected
      shrimp.
AB  - Infection of shrimp cells with white spot syndrome virus (WSSV) results in an
      increase in ribonucleotide reductase (RR) expression at the RNA level. In this
      article we further express and characterize the induction of a novel
      ribonucleotide reductase after WSSV infection of shrimp cells. A
      baculovirus/insect system was used to express the two recombinant protein
      subunits RR1 and RR2, and a DNA polymerase coupled RR activity assay showed a
      marked increase in ribonucleotide reductase activity when cell extracts
      containing recombinant RR1 and RR2 were combined. The same assay revealed that RR
      activity increased as infection advanced in the gills of experimentally infected
      shrimp. An increase in RR expression was also detected at the protein level in
      WSSV-infected shrimp cells. An immunocytochemistry assay by confocal laser
      scanning microscopy showed that in hemocytes collected from WSSV-infected shrimp,
      both of the subunit proteins (RR1 and RR2) were concentrated mainly around the
      nucleus, but only RR1 was detected inside it. All of these results suggest that
      WSSV RR is functionally involved during WSSV infection.

PMID- 12504570
TI  - Structural basis for ubiquitin-like ISG 15 protein binding to the NS1 protein of
      influenza B virus: a protein-protein interaction function that is not shared by
      the corresponding N-terminal domain of the NS1 protein of influenza A virus.
AB  - The N-terminal domains of the NS1 protein of influenza B virus (NS1B protein) and
      the NS1 protein of influenza A virus (NS1A protein) share one function: binding
      double-stranded RNA (dsRNA). Here we show that the N-terminal domain of the NS1B
      protein possesses an additional function that is not shared by its NS1A
      counterpart: binding the ubiquitin-like ISG15 protein that is induced by
      influenza B virus infection. Homology modeling predicts that the dimeric six
      helical N-terminal domain of the NS1B protein differs from its NS1A protein
      counterpart in containing large loops between helices 1 and 2 (loops 1 and 1')
      and between helices 2 and 3 (loops 2 and 2'). Mutagenesis establishes that
      residues located in loop 1/1' together with residues located in polypeptide
      segment 94-103 form the ISG15 protein-binding site of NS1B protein. Loop 1/1' is
      not required for dsRNA binding, which instead requires arginine residues R50,
      R53, R50', and R53' located in antiparallel helices 1 and 1'. Further, we
      demonstrate that the binding sites for RNA and protein are independent of each
      other. In particular, ISG15 and dsRNA can bind simultaneously; the binding of the
      ISG15 protein does not have a detectable effect on the binding of dsRNA, and vice
      versa.

PMID- 12504571
TI  - Cell-culture propagation of porcine enteric calicivirus mediated by intestinal
      contents is dependent on the cyclic AMP signaling pathway.
AB  - Enteric caliciviruses are emerging pathogens in humans and animals, but they do
      not replicate in cell culture except for the porcine enteric calicivirus (PEC)
      Cowden strain. The PEC Cowden strain grows in pig kidney (LLC-PK) cells, but only
      in the presence of intestinal contents (IC) from uninfected gnotobiotic pigs in
      the medium. In this study, we investigated the relationship between IC and growth
      of Cowden PEC. Pretreatment of cells or the virus with IC or transfection of
      viral RNA into cells did not induce virus growth unless the medium was
      supplemented with IC. Among modulators of cell signal transduction, the G protein
      uncoupler, suramin, adenylate cyclase (AC) inhibitor, MDL-12,330A, and the cAMP
      dependent protein kinase (PKA) inhibitor, N-(2-[bromocinnamulamino]ethyl)-5
      isoquinolinesulfonamide (NBEI) inhibited the effect of IC on virus growth for up
      to 72 h. These data indicate that PEC virus replication may be dependent on an
      initial cAMP signaling pathway induced by IC.

PMID- 12504572
TI  - The sequential introduction of HIV-1 subtype B and CRF01AE in Singapore by sexual
      transmission: accelerated V3 region evolution in a subpopulation of Asian CRF01
      viruses.
AB  - The rapid spread of the human immunodeficiency virus type 1 (HIV-1) circulating
      recombinant form (CRF) 01AE throughout Asia demonstrates the dynamic nature of
      emerging epidemics. To further characterize the dissemination of these strains
      regionally, we sequenced 58 strains from Singapore and found that subtype B and
      CRF01 were introduced separately, by homosexual and heterosexual transmission,
      respectively. Protein similarity scores of the Singapore CRF01, as well as all
      Asian strains, demonstrated a complex distribution of scores in the V3 loop--some
      strains had very similar V3 loop sequences, while others were highly divergent.
      Furthermore, we found a strong correlation between the loss of a V3 glycosylation
      site and the divergent strains. This suggests that loss of this glycosylation
      site may make the V3 loop more susceptible to immune surveillance. The
      identification of a rapidly evolving population of CRF01AE variants should be
      considered when designing new candidate vaccines and when evaluating breakthrough
      strains from current vaccine trials.

PMID- 12504573
TI  - Apoptosis modulation of Epstein-Barr virus-encoded latent membrane protein 1 in
      the epithelial cell line HeLa is stimulus-dependent.
AB  - Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is required for
      viral transformation and has been shown to protect lymphocytes from apoptosis.
      However, the effect of LMP1 on cells of epithelial origin remains poorly
      understood. Using the epithelial cell line HeLa in which the expression of LMP1
      is inducibly regulated by tetracycline, we demonstrate that apoptosis triggered
      by ligation of the death receptor, Fas, or by the chemotherapeutic agent,
      etoposide, is potentiated by LMP1. Apoptosis was assessed by nuclear condensation
      and activation of caspase-3-like enzymes with concomitant proteolysis of the
      nuclear caspase substrate, poly(ADP-ribose) polymerase. However, the effect of
      LMP1 in HeLa cells appeared to be stimulus-dependent since apoptosis induced by
      tumor necrosis factor (TNF) was inhibited. Moreover, we observed an upregulation
      of the zinc finger protein A20 and a decrease in expression of Bcl-2 upon
      induction of LMP1 in HeLa cells. Taken together, these data further our
      understanding of the function of LMP1 in epithelial cells and suggest that LMP1,
      similar to its mammalian homolog CD40, can exert opposing effects on cell
      survival depending on the nature of the apoptosis trigger.

PMID- 12504574
TI  - Epstein-Barr virus encoded interleukin-10 inhibits HLA-class I, ICAM-1, and B7
      expression on human monocytes: implications for immune evasion by EBV.
AB  - Monocytes and macrophages play a central role in viral infections, as a target
      for viruses and in activation of both innate and adaptive immune responses.
      Epstein-Barr virus (EBV) has evolved elaborate strategies to dampen the immune
      system and to persist within the host. There is evidence that the product of the
      BCRF-1 open reading frame of EBV, viral interleukin-10 (vIL-10), inhibits the
      capacity of monocytes/macrophages to induce T cell activation, but the full
      mechanism of this effect is unknown. To determine whether this effect might
      involve modulation of the expression of accessory molecules known to be important
      in T cell activation, we analyzed by flow cytometry the influence of vIL-10 on
      the basal as well as on IFN-gamma-induced up-regulation of HLA molecules, ICAM-1,
      and two members of the B7 family B7.1 (CD80) and B7.2 (CD86) at the surface of
      human monocytes. Viral IL-10 in a concentration-dependent manner inhibited both
      basal- and IFN-gamma-induced HLA-class II, ICAM-1 (basal levels of ICAM-2 and
      ICAM-3 is unaffected), CD80, and CD86 up-regulation when added simultaneously
      with IFN-gamma. In contrast, complete inhibition of HLA-class I expression on
      monocytes/macrophages occurred only when vIL-10 was present 2 h prior to the
      addition of IFN-gamma, implying that vIL-10 affects an early step in the IFN
      gamma signaling pathway. As both monocytes and macrophages can be infected by
      EBV, we propose that vIL-10-mediated impairment of monocyte/macrophage antigen
      presenting function could help the virus-infected cells to avoid detection by the
      host's T cells on one hand and contribute to its immunosuppressive properties on
      the other.

PMID- 12504575
TI  - Rabbit hemorrhagic disease virus: identification of a cleavage site in the viral
      polyprotein that is not processed by the known calicivirus protease.
AB  - The positive-strand RNA genome of the calicivirus rabbit hemorrhagic disease
      virus (RHDV) contains one long open reading frame (ORF) covering almost 95% of
      the genomic RNA. Translation of this ORF leads to a polyprotein that is
      proteolytically processed at eight sites. Site nos. 4 and 5 from the amino
      terminus are located within the protein p41 and obviously belong to alternative
      cleavage pathways leading to p23/2 and p18 or p29 and p13. Seven of the eight
      cleavage sites were identified before and the flanking sequences fulfill the
      requirements of the known RHDV protease, so that it is very likely that all
      theses sites are cleaved by this enzyme. The last unknown cleavage site was no.
      4, one of the two alternative sites within p41 that separates the nonstructural
      proteins p23/2 and the VPg precursor p18. Mutagenesis studies identified aspartic
      acid at position 936 and arginine at position 937 as the residues that flank the
      cleavage site. The sequence at the processing site is unusual for the RHDV 3C
      like protease since other sites display glutamic acid or glutamine at the P1 site
      and glycine, aspartic acid, or threonine at the P1' site. Expression of a
      polyprotein fragment lacking the viral protease revealed that the newly
      identified site is not cleaved by the RHDV protease but by an unknown proteolytic
      activity.

PMID- 12504576
TI  - Association of primate T-cell lymphotropic virus infection of pig-tailed macaques
      with high mortality.
AB  - Natural infection of humans with human T-cell lymphotropic virus type I (HTLV-I)
      and of old world nonhuman primates with the simian counterpart, STLV-I, is
      associated with development of neoplastic disease in a small percentage of
      individuals after long latent periods. HTLV-I is also the etiologic agent of a
      more rapidly progressive neurologic disease, HTLV-I-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). Macaques have been used
      experimentally in studies to evaluate HTLV-I candidate vaccines for efficacy, but
      no evidence of disease was observed. Here we report experimental infection of pig
      tailed macaques with STLV-I(sm) and HTLV-I(ACH), both of which were associated
      with a disease syndrome characterized by rapid onset, hypothermia, lethargy, and
      death within hours to days. Other pathologic sequelae included diarrhea, rash,
      bladder dysfunction, weight loss, and, in one animal, arthropathy. Both
      retroviruses were detected in the central nervous systems of some animals, either
      by culture or by direct antigen capture for p19 Gag in cerebrospinal fluid.
      Although virus was recovered throughout infection from peripheral blood
      mononuclear cells (PBMC), all infected macaques maintained low antiviral antibody
      titers and stable proviral burdens, which generally ranged between 10 and 100
      copies per 10(6) PBMC. However, of 13 macaques infected with HTLV-I(ACH) or STLV
      I(sm), seven animals (54%) died between 35 weeks and 412 years after infection.
      This unexpected high mortality within a relatively short time suggests that
      infection of pig-tailed macaques might be a useful model for studying immune
      responses to and pathologic events resulting from HTLV-I infection.

PMID- 12504577
TI  - Polymorphism in the infectious salmon anemia virus hemagglutinin gene: importance
      and possible implications for evolution and ecology of infectious salmon anemia
      disease.
AB  - Infectious salmon anemia (ISA) is an emerging disease in farmed Atlantic salmon
      with important commercial consequences. The pathogenicity of the ISA virus (ISAV;
      an orthomyxovirus) varies, observed as differences in disease development and
      clinical signs. A small polymorphic region (PR) in the ISAV genomic segment
      encoding the hemagglutinin (HA) has been described. An analysis of 33 HA gene
      sequences from historical and recent ISA outbreaks was performed, added to a
      selection of previously published HA sequences. A differential deletion model
      explaining the generation of HA polymorphism is proposed. The European ISAV
      sequences could be grouped according to deletion patterns in PR. Cell-culture
      replication and cytopathic effect varied between viruses from different PR
      groups. A rather complex epidemiology is suggested, as (a) HA sequences
      representing several PR variants were detected in three samples; (b) identical
      mutations occurred in different genetic lineages; and (c) large genetic
      differences were present in closely related viruses.

PMID- 12504578
TI  - Analysis, quantification, and evolutionary consequences of HIV-1 in vitro
      recombination.
AB  - HIV-1 recombination was studied in vitro by viral cocultivation of four
      combinations of strains of subtypes B, D, and F. Viral cocultivations were
      performed in MT-4 cells and maintained for 22 days. The parental and recombinant
      forms were quantified by a specific PCR system in an env fragment of 2500
      nucleotides. On day 5, there was a close correlation between the proportion of
      recombination and the genetic distance between strains. In three of the four
      viral combinations studied, a steady increase in the proportion of recombinant
      genomes was observed over time. This rise coincided with the progressive loss of
      one of the parental strains, resulting in less diverse viral populations.
      Nucleotide sequencing of biological recombinant clones from the B/D cocultivation
      revealed a higher number of recombination events in pol than in env gene, and an
      increasing number of crossovers per clone with time.

PMID- 12504579
TI  - Adaptation of a CXCR4-using human immunodeficiency type 1 NDK virus in intestinal
      cells is associated with CD4-independent replication.
AB  - Infection of epithelial colon carcinoma cell line HT29 with human
      immunodeficiency virus type 1 (HIV-1) NDK, a subtype D virus highly cytopathic
      for CD4-positive lymphocytes, results in the selection of HIV-1 variants, 1000
      times more infectious for CD4(-) intestinal cells than the parental virus. Here,
      we demonstrate that the envelope gene of intestinal cell-adapted virus conferred
      to recombinant clone HIV-1 iNDK the ability to utilize CXCR4 without CD4 while
      retaining its tropism for CD4 lymphocytes. Among the major genetic changes
      required for infection of intestinal cells and CD4 independence, two potential N
      glycosylation sites appeared as a result of the extension of five amino acids in
      the V1/V2 region and three amino acid changes ((296)KYT --> (296)NNI) were
      identified in the V3 loop of HIV-1 iNDK gp120. Our studies suggest that CD4
      independent use of CXCR4 can be mediated by different adaptive changes related to
      the microenvironment of CD4(-) cell.

PMID- 12504580
TI  - Alteration of intrahepatic cytokine expression and AP-1 activation in transgenic
      mice expressing hepatitis C virus core protein.
AB  - Hepatitis C virus (HCV) infection often leads to the development of
      hepatocellular carcinoma (HCC), but its molecular mechanism has not been clearly
      elucidated. Previously, transgenic mice constitutively expressing HCV core
      protein have been shown to develop HCC, suggesting a pivotal role of the core
      protein in hepatocarcinogenesis. Here, we analyzed the expression of cytokines
      associated with a variety of cellular processes, including cell proliferation, in
      the mouse model for HCV-associated HCC to define the molecular events prior to
      oncogenesis. The expression of tumor necrosis factor-alpha and interleukin-1beta
      was increased at both protein and mRNA levels. In addition, the activities of c
      Jun N-terminal kinase and activator protein-1 (AP-1), downstream effectors, were
      enhanced, while IkappaB kinase or nuclear factor-kappaB activities were not
      enhanced. Thus, the altered in vivo expression of cytokines with AP-1 activation
      in consequence to the core protein expression may contribute to
      hepatocarcinogenesis in persistent HCV infection.

PMID- 12504581
TI  - Identification of a unique family of F-box proteins in atadenoviruses.
AB  - Ovine adenovirus isolate 287 (OAdV-7) is the prototype of the atadenoviruses, a
      genus whose strategy for infection and replication is still being elucidated. A
      transcription unit at the right end of the genome contains four related genes
      (ORFs RH1, 2, 4, and 6), at least three of which are nonessential for replication
      in vitro. Related genes are also present in the genomes of bovine and avian
      atadenoviruses. To investigate how these apparently redundant genes are decoded,
      a more detailed transcription map of the right end of the OAdV-7 genome has been
      deduced. Eight transcripts that were derived from a promoter in the terminal
      repeat sequence were identified. Five were potentially bicistronic. The
      transcripts could encode all the potential proteins of the region subject to
      efficient reinitiation of translation. However, the most interesting and
      surprising finding in this work was that the related RH proteins carry an F-box
      motif. This was first identified in OAdV-7 RH1 and subsequently found in RH2, 4,
      and 6 proteins and the related reading frames from the bovine and avian
      atadenoviruses. Although very rare among viral proteins, several hundred cellular
      proteins contain F-box motifs. F-box proteins facilitate the degradation of a
      variety of important regulatory proteins via SCF ubiquitin ligase complexes.
      Thus, it appears that atadenoviruses have adopted a strategy to regulate a key
      cellular pathway(s) that distinguishes them from the other adenovirus genera and
      from most viruses in general.

PMID- 12504582
TI  - Host-dependent recombination of a Tomato bushy stunt virus coat protein mutant
      yields truncated capsid subunits that form virus-like complexes which benefit
      systemic spread.
AB  - This study examined the contribution of the Tomato bushy stunt virus (TBSV) coat
      protein (CP) and its corresponding RNA to systemic infection of plants. Compared
      to results obtained with a mutant lacking the 5'-half of the CP gene, the
      presence of those CP-RNA sequences in another mutant benefited TBSV infection on
      Nicotiana benthamiana even though wild-type CP expression was eliminated by
      introduction of a small out-of-frame deletion. RT-PCR of viral RNA associated
      with rapid infections established by this CP frameshift deletion mutant revealed
      that in planta recombination had provided the progeny with the ability to express
      a truncated CP (tCP) with a block of N-proximal 30 residues deleted from the 66
      amino acid RNA-binding domain. Subsequent biochemical characterizations revealed
      the presence of large ribonucleoprotein complexes that were shown to contain
      viral RNA as well as the approximately 38-kDa tCP. Electron microscopic
      examination of purified complexes showed particle-like structures that were
      nonuniform in size and shape compared to wild-type TBSV particles. Inoculation of
      pepper with the tCP-containing ribonucleoprotein complexes resulted in a rapid
      systemic infection similar to that caused by wild-type TBSV. In contrast,
      infections established in pepper by the original CP frameshift deletion mutant
      transcripts were restricted to inoculated leaves and did not yield recombinants
      capable of systemically infecting this host. In summary, TBSV possesses the
      flexibility to form alternative virion-like structures even if a substantial
      portion of the RNA-binding domain is deleted from the CP; mutants producing the
      tCP-containing particle-like structures are more effective for virus spread than
      those devoid of CP expression; and recombination events to produce the
      alternative tCP-RNA complexes are host-dependent.

PMID- 12504583
TI  - Low-neurovirulence Theiler's viruses use sialic acid moieties on N-linked
      oligosaccharide structures for attachment.
AB  - Low-neurovirulence BeAn and DA Theiler's murine encephalomyelitis viruses (TMEV)
      cause persistent infection in the central nervous system (CNS) of susceptible
      mouse strains, leading to an inflammatory demyelinating process. A role for a
      specific virus-cell receptor interaction has been posited to explain why only low
      and not high-neurovirulence TMEV cause persistent CNS infections. Low- but not
      high-neurovirulence TMEV use sialic acid for attachment to mammalian cells, which
      may contribute to neurovirulence attenuation and viral persistence. Analysis of
      BeAn virus binding and infection in cells with altered (mutated) cell-surface
      expression of sialic acid containing glyconjugates indicated that both binding
      and infection are mediated entirely by N-linked glycoproteins. By contrast, GDVII
      virus binding and infection appears to be dependent only in part on N-linked
      glycoproteins and not on O-linked glycoproteins or glycolipids. These results
      indicate that low-neurovirulence BeAn virus uses a sialic acid moiety expressed
      on an N-linked carbohydrate of a glycoprotein that serves as the protein entry
      receptor.

PMID- 12504584
TI  - Intraepithelial DNA immunisation with a plasmid encoding a codon optimised COPV
      E1 gene sequence, but not the wild-type gene sequence completely protects against
      mucosal challenge with infectious COPV in beagles.
AB  - DNA plasmids encoding the open reading frames of canine oral papillomavirus
      (COPV) nonstructural early genes E1, E2, or E7 protein were delivered into both
      oral mucosal and cutaneous epithelial sites in beagle dogs using particle
      mediated immunotherapeutic delivery (PMID) technology. Control dogs were
      vaccinated with plasmid encoding either hepatitis B virus surface antigen (HBVs)
      or COPV L1. Using a prophylactic immunisation protocol, a priming dose of plasmid
      DNA was followed by a booster dose 6 weeks later. Four weeks after boost, all
      dogs were challenged with infectious COPV particles. Following viral challenge,
      as shown previously (M. A. Stanley et al., 2001, Vaccine 19, 2783-2792), mucosal
      papillomas developed in the negative-control HBVs vaccinated dogs, but all
      animals in the COPV L1 group were fully protected from disease development. In
      the early gene-vaccinated groups five of six in the E1-vaccinated dogs, two of
      six in E2-vaccinated dogs, and three of six in the E7-vaccinated beagles
      developed oral papillomas. Compared to the HBVs negative-control group the oral
      papillomas that did develop in the early-gene vaccinated beagles were
      significantly smaller, shorter in duration, and fewer in number. Taken together
      the disease burden was markedly reduced and this was statistically significant.
      In a second experiment one group of animals was vaccinated with plasmid encoding
      the wild-type COPV E1 gene, and a separate group was vaccinated with plasmid
      encoding a synthetic codon-optimised COPV E1 gene sequence. None of the codon
      optimised E1-vaccinated animals developed papillomas at any challenge site.
      However, all animals vaccinated with wild-type E1 had papillomas. These data
      suggest that immunisation by PMID with papillomavirus early genes can
      significantly impact upon subsequent disease development and that full protection
      can be achieved using improved vectors encoding codon-optimised gene sequences
      perhaps emphasizing the importance of antigen load in the generation of
      protective responses to papillomavirus proteins.

PMID- 12504585
TI  - Mechanism of DI RNA formation in tombusviruses: dissecting the requirement for
      primer extension by the tombusvirus RNA dependent RNA polymerase in vitro.
AB  - Tombusviruses, which are positive-strand RNA viruses of plants, frequently
      generate defective interfering (DI) RNAs that consist of three to four
      noncontiguous segments of the parental RNA. Replicase jumping was postulated to
      cause multiple deletions leading to the de novo formation of DI RNAs in planta.
      This model was tested using a partially purified RNA-dependent RNA polymerase
      (RdRp) preparation from tombusvirus-infected plants in vitro. The tombusvirus
      RdRp was capable of primer extension without the need for sequence
      complementarity between the primer and the acceptor template in vitro, although
      the most efficient primer extension was obtained with primers forming a 5-bp
      duplex with the acceptor region. Primers forming 14- to 20-bp duplexes with the
      acceptor region were used less efficiently by the tombusvirus RdRp in vitro. In
      addition, primers with 3' noncomplementary nucleotides were also extended by the
      tombusvirus RdRp, albeit with a reduced efficiency. The preference of the
      tombusvirus RdRp for short base-paired primers in vitro is consistent with the
      lack of extended sequence similarities at the junction sites in the de novo
      generated tombusvirus-associated DI RNAs. The in vitro experiments also revealed
      that the acceptor region plays a significant role in primer extension. Comparison
      of tombusvirus-derived, heterologous and artificial acceptor regions revealed
      that the conserved regions present in DI RNAs are the best acceptor regions when
      they are available in the minus-strand orientation. These data suggest that
      recombination/deletion events may be more frequent at some regions, rather than
      occurring randomly throughout the parental genome. In addition, these findings
      support a model that predicts a higher frequency of replicase jumping, i.e.,
      recombination/deletion events, during plus-strand synthesis than during minus
      strand synthesis.

PMID- 12504586
TI  - Clonotype tracking of TCR repertoires during chronic virus infections.
AB  - Human viral infections such as HIV and EBV typically evoke a strong and diverse
      CD8(+) T cell response. Relatively little is known about the extent to which TCR
      repertoire evolution occurs during viral infection or how repertoire evolution
      affects the efficacy of the CD8(+) T cell response. In this study we describe a
      general approach for tracking TCR repertoire evolution during viral infection.
      IFNgamma surface capture and MHC class I tetramer staining were independently
      used to isolate EBV-specific CD8(+) T cells from peripheral blood. Anchored RT
      PCR and clonotype TCR repertoire analysis were performed immediately after
      isolating the cells. We find that the TCR repertoires of the IFNgamma-secreting
      and MHC class I tetramer staining populations were similar. In one subject a
      detailed analysis of the TCR repertoire during the first year of EBV infection
      was performed and over 600 TCR sequences targeting an EBV-immunodominant epitope
      were analyzed. Although some repertoire evolution occurred during the year, in
      general, the degree of repertoire drift was small. TCR repertoire analysis for an
      HIV-immunodominant epitope revealed a highly conserved amino acid motif in the
      Dbeta region of TCR that recognizes the epitope and suggested that T cell
      precursor frequency influences which epitopes are targeted early in HIV
      infection. This methodology, which allows one to sort antigen-specific T cells
      based on different functional assays and to obtain a snapshot of their TCR
      repertoire with relative ease, should lead to a richer understanding of the rules
      underlying antigen recognition and T cell evolution during viral infection.

PMID- 12504587
TI  - Inhibition by lectins of glutamate receptor desensitization is determined by the
      lectin's sugar specificity at kainate but not AMPA receptors.
AB  - The lectin Concanavalin A (ConA) has long been known to potentiate current
      responses of native and recombinant ionotropic glutamate receptors (iGluRs),
      apparently by inhibition of receptor desensitization. We compared the effects of
      a broad range of lectins with different carbohydrate specificities on recombinant
      AMPA (GluR1) and kainate receptors (GluR6) expressed in Xenopus oocytes.
      Interestingly, the extent of inhibition of desensitization appears to depend on
      the sugar preference of lectins at kainate (KA) receptors, but not at alpha-amino
      3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. None of the
      lectins potentiated current responses at non-glycosylated GluRs produced in
      tunicamycin-treated oocytes, demonstrating the requirement of lectin interaction
      with carbohydrate moieties of the receptors. At AMPA receptors, potentiation of
      current responses afforded by ConA and the well-known inhibitor of
      desensitization, cyclothiazide (CTZ), are additive, suggesting that the lectin
      and CTZ act independently. Current amplitudes of GluR1(L479Y), a nondesensitizing
      mutant, however, could not be further increased by ConA.

PMID- 12504588
TI  - Robo1 and Robo2 are homophilic binding molecules that promote axonal growth.
AB  - In the present study we show that following transfection in 3T3 cells, human
      Robo1 and Robo2 stimulate neurite outgrowth from Robo-positive neurons (retinal
      neurons and olfactory neurons), but have no effect on Robo-negative neurons
      (cerebellar granule cells). The neurite outgrowth response was inhibited by an
      antibody raised against the first Ig domain of Robo1/2 or by soluble Robo-Fc
      chimera. Furthermore, we show that the extracellular domains of Robo1 and Robo2
      are homophilic adhesion molecules that can also interact with each other. These
      data suggest a wider range of functions for the Robo family in the development of
      the nervous system and provide novel insights into the molecular basis for the
      phenotypes observed in Robo mutants in Drosophila, C. elegans, and zebrafish.

PMID- 12504589
TI  - Human glioma cells and undifferentiated primary astrocytes that express aberrant
      EAAT2 mRNA inhibit normal EAAT2 protein expression and prevent cell death.
AB  - Abnormal splicing of astroglial glutamate transporter EAAT2 mRNA has been
      suggested to account for the loss of EAAT2 protein in amyotrophic lateral
      sclerosis (ALS) and Alzheimer's disease (AD). We have identified several clones
      of human U251 glioma cells which express varying amounts of aberrantly spliced
      EAAT2 mRNA; these clones do not express any detectable EAAT2 protein. When the
      wild-type EAAT2 cDNA was expressed in each of these clones, we found that the
      amount of EAAT2 protein inversely correlated with the levels of endogenous
      aberrant EAAT2 mRNA. We also observed that ectopic expression of normal EAAT2
      protein is toxic to U251 cells as well as to undifferentiated primary astrocytes.
      We conclude that expression of aberrant EAAT2 mRNA may be one possible mechanism
      to repress normal EAAT2 protein expression. The implication of this study for the
      mechanisms of EAAT2 protein loss in ALS and AD is discussed.

PMID- 12504590
TI  - Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells,
      and show activation of an mTOR pathway.
AB  - Cortical tubers are developmental brain malformations in the tuberous sclerosis
      complex (TSC) that cause epilepsy and autism in TSC patients whose pathogenesis
      is uncertain. Tsc2 null murine neuroepithelial progenitor (NEP) cells display
      persistent growth when growth factors are withdrawn, express GFAP at high levels,
      and have reduced expression of a set of early neuronal lineage markers. Tsc2 null
      NEP cells exhibit aberrant differentiation into giant cells that express both
      beta III-tubulin and GFAP and that are morphologically similar to giant cells in
      human tubers. Tsc2 null giant cells and tuber giant cells have similar
      transcriptional profiles. Tsc2 null NEP cells express high levels of
      phosphorylated S6kinase, S6, Stat3, and 4E-BP-1, which is reversed by treatment
      with rapamycin, an inhibitor of mTOR. We conclude that giant cells in human
      tubers likely result from a complete loss of TSC2 expression and activation of an
      mTOR pathway during cortical development.

PMID- 12504591
TI  - The insulin receptor substrate IRSp53 links postsynaptic shank1 to the small G
      protein cdc42.
AB  - The multidomain shank/ProSAP/SSTRIP proteins are major scaffold proteins in
      glutamatergic synapses in the mammalian brain; expression of shank1/SSTRIP in
      hippocampal neurons induces morphological changes in dendritic spines, suggesting
      that shank1 is involved in synapse formation and activity-dependent changes of
      synaptic structure. Using part of the proline-rich region of shank1 in a yeast
      two hybrid screen, we identified the insulin receptor substrate IRSp53 as an
      interaction partner. Overlay assays verified a strong interaction between a
      proline-rich sequence (residues 911-940) in shank1 and the SH3 domain of IRSp53.
      When coexpressed in HEK cells, shank1 colocalizes with IRSp53 in intracellular
      structures, preventing targeting of IRSp53 to filopodia which are induced by
      IRSp53 expression in the absence of shank1. IRSp53 also binds to the activated
      form of the small G-protein cdc42. Interestingly, IRSp53 coprecipitates with
      shank1 from transfected HEK cells in a small G-protein-regulated manner. Thus,
      IRSp53 constitutes a cdc42-regulated ligand for shank1 which may provide a
      molecular basis for small G-protein mediated effects on the structure of the
      postsynaptic complex.

PMID- 12504592
TI  - Disruption of PLC-beta 1-mediated signal transduction in mutant mice causes age
      dependent hippocampal mossy fiber sprouting and neurodegeneration.
AB  - Aberrant reorganization of hippocampal mossy fibers occurs in human temporal lobe
      epilepsy and rodent epilepsy models. We generated a mouse model showing massive
      late-onset aberrant mossy fiber sprouting in the adult hippocampus. The mutation
      in this mouse model derives from an intronic insertion of transgene DNA in the
      mouse PLC-beta1 gene (PLC-beta 1(-/-)(TC) mutation) leading to a splice mutation
      of the PLC-beta 1 gene and a complete loss of downstream PLC-beta 1 expression.
      PLC-beta 1(-/-)(TC) mutants develop a loss of NMDA-receptors in the stratum
      oriens of region CA1, apoptotic neuronal death, and reduced hippocampal PKC
      activity. The phenotype of these mice further consists of a late-onset
      epileptiform hyperexcitability, behavioral modifications in a radial maze and in
      an open field, female nurturing defect, and male infertility. In the present
      study, we provide evidence that the arising of the behavioral phenotype in PLC
      beta 1(-/-)(TC) mice correlates in time with the development of the aberrant
      mossy fiber projections and that the disruption of the PLC-beta 1-mediated signal
      transduction pathway may lead to a functional cholinergic denervation, which
      could cause hippocampal remodeling and, in consequence, epileptiform
      hyperexcitability.

PMID- 12504593
TI  - Soluble interleukin-6 (IL-6) receptor/IL-6 fusion protein enhances in vitro
      differentiation of purified rat oligodendroglial lineage cells.
AB  - We investigated the effects of a chimeric protein (IL6RIL6 chimera) containing
      interleukin-6 (IL-6) fused to its soluble receptor (sIL-6R) on the proliferation
      and/or differentiation of rat oligodendrocyte progenitor cells (OPCs) and on
      oligodendrocyte survival. Exposure of OPCs to IL6RIL6 chimera for 48 h induced a
      dose-dependent decrease of bromodeoxyuridine (BrdU) incorporation. IL6RIL6
      chimera treatment for 48 h also strongly increased the reduction of the
      tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) by mitochondrial enzymes and enhanced
      oligodendrocyte staining with a mitochondrial fluorescent dye. A strong, dose
      dependent increase in the number and length of processes immunostained for early
      (galactocerebroside) or late (myelin basic protein) oligodendrocyte
      differentiation markers was revealed after OPC treatment with IL6RIL6 chimera for
      2-7 days, respectively. Moreover, treatment with IL6RIL6 chimera improved
      oligodendrocyte survival. The chimera-induced increase of oligodendrocyte
      arborization was mimicked, although with lower efficacy, by ciliary neurotrophic
      factor (CNTF) but not by IL-6 and was reduced in the presence of a gp130 soluble
      peptide which is able to inhibit the gp130-mediated signals of the IL-6/sIL-6R
      complex. Oligodendrocyte treatment with IL6RIL6 chimera for 30 min induced both
      signal transducer and the activator of transcription-1 (STAT-1) and STAT-3
      phosphorylation and nuclear translocation. We conclude that, by interacting with
      membrane gp130 and possibly by activating Janus kinase/STAT pathways, IL6RIL6
      chimera induces OPCs to differentiate into mature oligodendrocytes, promotes
      their survival, and could deserve investigation as a therapeutic strategy for
      enhancing remyelination.

PMID- 12504594
TI  - Nicotinic regulation of CREB activation in hippocampal neurons by glutamatergic
      and nonglutamatergic pathways.
AB  - Activity-dependent gene expression is essential for form and function in the
      nervous system. Best understood is the role of glutamatergic signaling in
      controlling such events, but nicotinic signaling can also regulate transcription.
      We show here that nicotine can alter gene expression in rat hippocampal neurons,
      as reflected by activation of the transcription factor CREB and appearance of the
      immediate early gene product c-Fos. The process depends on both CaM and MAP
      kinases and on calcium release from internal stores. Part of the nicotinic effect
      is mediated via glutamatergic transmission, even in the absence of action
      potentials. Voltage-gated calcium channels are not necessary for nicotine-induced
      activation of CREB in hippocampal neurons. The low levels of sustained nicotinic
      stimulation required for transcriptional effects are consistent with those likely
      to be achievable either by the normal septal cholinergic innervation of the
      hippocampus or by repeated tobacco usage.

PMID- 12504595
TI  - Tenascin-R induces actin-rich microprocesses and branches along neurite shafts.
AB  - The formation of protrusions along the shaft of neurites might be important in
      the establishment and refinement of neuronal connections during development. In a
      search for extracellular signals that affect the formation of microprocesses
      along neurites we found that the ECM glycoprotein tenascin-R (TN-R) but not other
      ECM glycoproteins increased the percentage of tectal neurons with actin-rich
      microprocesses and side branches. Longer actin-based microprocesses were also
      invaded by microtubuli in their proximal part. The formation of microprocesses by
      TN-R extending laterally along the neuritic shaft was time- and dose-dependent.
      In addition to the induction of microprocesses, TN-R increased the size of the
      growth cone of tectal neurons. A cross-species experiment in combination with
      blocking antibodies demonstrated that the TN-R-induced effects are mediated by
      the Ig superfamily member contactin. These observations suggest that TN-R via its
      neuronal receptor contactin might induce a transition from long-distance growth
      of tectal interneurons to differentiation, including the formation of
      microprocesses.

PMID- 12504596
TI  - Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes
      mediates neuroprotective activity of transforming growth factor-beta 1 against
      NMDA-induced necrosis.
AB  - The intravenous injection of the serine protease, tissue-type plasminogen
      activator (t-PA), has shown to benefit stroke patients by promoting early
      reperfusion. However, it has recently been suggested that t-PA activity, in the
      cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present
      study has dealt with the role of the t-PA inhibitor, PAI-1, in the
      neuroprotective activity of the cytokine TGF-beta1 and focused on the
      transduction pathway involved in this effect. We demonstrated that PAI-1,
      produced by astrocytes, mediates the neuroprotective activity of TGF-beta 1
      against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA
      inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by
      modulating the NMDA-evoked calcium influx. Finally, we showed that the activation
      of the Smad3-dependent transduction pathway mediates the TGF-beta-induced up
      regulation of PAI-1 and subsequent neuroprotection. Overall, this study
      underlines the critical role of the t-PA/PAI-1 axis in the regulation of
      glutamatergic neurotransmission.

PMID- 12504597
TI  - Regional specification of neurosphere cultures derived from subregions of the
      embryonic telencephalon.
AB  - We have studied the molecular specification of precursor cells in expanded
      neurosphere cultures derived from distinct subregions of the embryonic mouse
      telencephalon. These regionally derived cultures exhibited differential responses
      to the mitogens EGF and bFGF, suggesting that the precursors in these cultures
      were differentially specified as is the case in situ. To examine this further,
      cultures from each of the telencephalic subregions were expanded in both EGF and
      bFGF before differentiation. The neurons produced displayed molecular phenotypes
      similar to those normally derived from each of these regions in vivo. Moreover,
      analysis of gene expression in the undifferentiated cultures showed that the
      regionally derived neurospheres express many of the same developmental control
      genes as their in vivo counterparts. Taken together, the present findings suggest
      that precursor cells in neurosphere cultures, derived from distinct subregions of
      the embryonic telencephalon, maintain at least certain aspects of their molecular
      specification, even after significant expansion in vitro.

PMID- 12504598
TI  - Association of LAR-like receptor protein tyrosine phosphatases with an enabled
      homolog in Hirudo medicinalis.
AB  - Receptor protein tyrosine phosphatases (RPTPs) are thought to play important
      functions in pathfinding and target recognition by growing neuronal processes.
      The leech RPTPs HmLAR1 and HmLAR2 are expressed selectively by central neurons,
      Comb cells, and peripheral muscle tissues in the Hirudo medicinalis embryo. To
      explore the functions of HmLARs, we have sought to determine their physiological
      substrates. We report here the cloning and embryonic expression of Lena, the
      leech homolog of Enabled, a cytosolic protein implicated in actin-based cell
      motility. Lena is expressed in embryonic central neurons and in the Comb cell. We
      present experimental evidences indicating that Lena associates selectively with
      the intracellular domain of HmLAR1 and HmLAR2. Additionally, RNA interference
      (RNAi) of HmLAR1 in intact leech embryos leads to the hyperphosphorylation of
      Lena. We propose, therefore, that Lena is an in vivo substrate of HmLAR1 in
      neurons and perhaps of HmLAR2 in the Comb cells.

PMID- 12504599
TI  - Pituitary adenylate cyclase-activating polypeptide induces astrocyte
      differentiation of precursor cells from developing cerebral cortex.
AB  - Ciliary neurotrophic factor and bone morphogenetic proteins induce
      astrocytogenesis in the developing rat brain by stimulating STAT- and Smad
      dependent signaling, respectively. We previously found that stimulation of the
      cAMP-dependent signaling pathway also triggers differentiation of cerebral
      cortical precursor cells into astrocytes, providing an additional mechanism to
      promote astrocyte differentiation. In this study, we show that pituitary
      adenylate cyclase-activating polypeptide (PACAP), but not the related vasoactive
      intestinal peptide, induces astrocyte differentiation of cortical precursor
      cells, even after a transient exposure. Cortical precursors were found to express
      predominantly the short isoform of the PACAP-specific PAC1 receptor, which
      couples to adenylate cyclase. Consistent with this notion, we determined that
      exposure of cortical precursors to PACAP resulted in a dose-dependent increase in
      cAMP production. Pretreatment of cells with the cAMP antagonist Rp-cAMPS
      prevented astrocyte differentiation. Thus, PACAP acts as an extracellular signal
      to trigger cortical precursor cell differentiation into astrocytes via
      stimulation of intracellular cAMP production.

PMID- 12504600
TI  - Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in
      spinal dorsal horn.
AB  - Several lines of evidence suggest that the brain-derived neurotrophic factor
      (BDNF) acts as central pain neuromodulator. We examined the ability of different
      types of peripheral stimulation to activate the BDNF high-affinity receptor,
      TrkB, in the spinal cord. We found that noxious chemical, mechanical, or thermal
      stimuli, but not innocuous stimuli, caused Trk phosphorylation in the spinal
      cord. These changes were rapid and transient and restricted to somatotopically
      appropriate spinal segments. We observed, both in vitro and in vivo, that
      exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in
      the development of acute pain. Finally, we found that sequestering BDNF in vivo
      with a TrkB-IgG fusion molecule significantly reduced the activation of ERK
      evoked by noxious stimulation. These data suggest that BDNF, once released with
      activity from primary afferent nociceptors, exerts a neuromodulatory role in pain
      processing through stimulation of postsynaptic TrkB receptors and subsequent
      activation of ERK.

PMID- 12504601
TI  - Enteroviral infections in primary immunodeficiency (PID): a survey of morbidity
      and mortality.
AB  - We have explored the natural history of enteroviral infection in patients with
      primary antibody deficiency by surveying both published and unpublished case
      reports before the new anti-enteroviral drug, pleconaril, was available. Many
      different enteroviruses were involved, Echovirus 11 being the most common. The
      central nervous system was nearly always involved, with evidence of systemic
      involvement of muscle and/or liver and/or joints in about 40% of patients.
      Neurological symptoms and signs varied with minor or no changes in the cerebro
      spinal fluid. There was high morbidity and mortality; a third of polio cases
      (usually vaccine related), and nearly half of non-polio infected patients died;
      about 40% of survivors of the initial illness had long-term neurological
      symptoms. Prophylactic immunoglobulin therapy did not prevent infection but these
      patients were on lower doses as compared to current recommendations. Our data
      provides a useful background for assessing the efficacy of new anti-viral
      treatment in this condition.

PMID- 12504602
TI  - Long-term follow-up study of HTLV-I infection in bottle-fed children born to
      seropositive mothers.
AB  - Human T-lymphotropic virus Type-I (HTLV-I) infects children via mother's milk.
      Infection of Human T-lymphotropic virus Type-I (HTLV-I) was investigated by long
      term follow-up surveys of modified milk-fed children. Our observations of
      modified milk-fed infants revealed that: 1 of 154 (0.6%) at year 1, 5 of 129
      (3.9%) at 1.5 years, and 5 of 108 (4.6%) at year 2 were anti-HTLV-I antibody
      positive. No infants or children became newly antibody-positive thereafter.
      Modified milk feeding could prevent the HTLV-I infection of infants from mothers
      in many cases, however the infants who had became anti-HTLV-I antibody-positive
      due to established infection by the age 2 remained positive at age 11-12 with
      persistent infections. Modified milk-fed infants who had been born from HTLV-I
      seropositive mothers did not show that they had complete protection from HTLV-I
      infection, but a low infection rate was seen, showing that modified milk feeding
      is useful to protect from HTLV-I infection.

PMID- 12504603
TI  - Infantile herpes simplex encephalitis: diagnostic features and differentiation
      from non-accidental injury.
AB  - OBJECTIVES: Neonatal herpes simplex virus (HSV) encephalitis is rare, but
      associated with considerable morbidity and mortality. After a baby, subsequently
      proven to have HSE, had initially been diagnosed as non-accidental injury (NAI),
      we reviewed the clinical features and radiology of infants with HSE recently
      diagnosed by our laboratory. METHODS: Screening of cerebrospinal fluid (CSF)
      samples sent to Oxford for HSV polymerase chain reaction (PCR) analysis, from
      wide range of British hospitals, identified HSV infected infants. After a
      diagnosis was made, the case notes and neuroradiology (where available) were
      reviewed and a limited follow-up was undertaken. RESULTS: Thirteen infants had
      HSV encephalitis (HSE), which in four followed a relapsing course. On subsequent
      assessment six infants had neurological sequelae, six appeared to be normal, and
      one was lost to follow-up. Neither a history of primary HSV infection in
      pregnancy, nor skin lesions in the baby, were helpful diagnostically. Magnetic
      resonance imaging indicated haemorrhage in the cortex, but no subdural
      haematomata, a hallmark of NAI, in 5/6 infants. CONCLUSIONS: The early clinical
      features of HSE and NAI may be indistinguishable. As early diagnosis is
      important, infants with an unidentified encephalopathic illness should be
      examined by neuroradiology and their CSF tested for HSV DNA. Together these
      examinations can confirm and differentiate between those two conditions.
      Relapsing HSE may mimic recurrent encephalopathy caused by multiple NAIs.

PMID- 12504604
TI  - Nosocomial infection and related risk factors in a general surgery service: a
      prospective study.
AB  - OBJECTIVES: The aim of this study was to quantify the frequency of nosocomial
      infection in the general surgery service of a tertiary-care hospital and to
      identify associated risk factors. METHODS: A prospective, longitudinal,
      descriptive and analytical study was made from January 1995 to December 1998 of a
      clinical cohort of 2794 patients who underwent a surgical procedure with a post
      surgery stay of more than 48 h. The criteria for infection were those defined by
      the Center for Disease Control and Prevention (CDC) of the USA. RESULTS: The most
      frequent nosocomial infection was surgical infection (SI), with a global
      cumulative incidence (CI) of 7.7%, ranging from 3.4% for clean surgery to 23.7%
      for dirty surgery. The next most frequent were urinary tract infection (UTI) and
      bacteremia (1.5%) and nosocomial pneumonia (NP) (0.5%). The global CI of SI
      decreased from 11.7% in 1995 to 4% in 1998. An ASA classification higher than 2
      multiplied the risk of SI by 1.76; with respect to UTI multiplied the risk by
      2.13; the risk of NP by 5.93 and multiplied the risk of B by 4.72. CONCLUSIONS:
      The most frequent nosocomial infection was surgical infection. An ASA higher than
      2, the stay prior to surgery; the number of days with a urinary catheter, with a
      central venous catheter and with mechanical ventilation; as well as the
      improvement in the use of antimicrobial prophylaxis, were all factors that
      influenced the frequency of nosocomial infection.

PMID- 12504605
TI  - Epidemiology of penicillin-resistant pneumococci in a Merseyside Health District
      over a 14-year period.
AB  - OBJECTIVES: To determine the prevalence and epidemiology of penicillin
      resistantStreptococcus pneumoniae isolates in the St Helens and Knowsley Health
      District of Merseyside. METHODS: Penicillin-resistant pneumococci were isolated
      from clinical samples taken from 549 patients between January 1987 and December
      2000. Patient profile, bacterial serotype and resistance patterns were analysed.
      RESULTS: Between January 1987 and December 2000, the prevalence of penicillin
      resistant pneumococci increased from 1.4% to a peak of 12.9% in 1997,
      subsequently falling to 8.9%. High-level penicillin resistance was found in 243
      (44.3%) of the isolates. Two hundred and eighty isolates were from children (mean
      age 2.2 years), of whom only 25% were clinically infected. Two hundred and sixty
      nine isolates were from adults (average age 68.4 years) of whom 88% were
      infected. Over 65% of isolates were community acquired with 53% of patients
      having received antibiotics in the 3 months prior to their first isolate. Twenty
      six per cent of patients had underlying disease of the respiratory tract. The
      changing evolution of serotypes over the 14 years of the study was associated
      with changes in sensitivity patterns. Serotype 9 was the most common serotype
      (36%). CONCLUSIONS: The study demonstrates the evolution of penicillin resistance
      in the patient population of this District over the past 14 years.

PMID- 12504606
TI  - Antibiotic prescribing and penicillin-resistant pneumococci in a Merseyside
      Health District.
AB  - OBJECTIVES: To measure the effects of antibiotic prescribing changes in the
      community on the prevalence of penicillin-resistant pneumococci. METHODS:
      Penicillin-resistant pneumococci were isolated from clinical samples taken from
      549 patients between January 1987 and December 2000. Changes in the percentage of
      penicillin-resistant pneumococci isolated over the 14-year period and changes in
      prescribing practices were determined. RESULTS: Between January 1987 and December
      2000, the prevalence of penicillin resistant pneumococci increased from 1.4% to a
      peak of 12.9% in 1997, subsequently falling to 8.9% after changes in antibiotic
      prescribing practices in the community. Over 65% of isolates were community
      acquired with 53% of patients having received antibiotics in the 3 months prior
      to their first isolate. Thirteen patients had a history of recent travel abroad.
      CONCLUSION: Reduction in antibiotic prescribing in general practice was followed
      by a reduction in the prevalence of penicillin-resistant pneumococci.

PMID- 12504607
TI  - Enhanced surveillance of campylobacter infection in the North West of England
      1997-1999.
AB  - OBJECTIVES: To identify sources and routes of infection for sporadic cases of
      campylobacter infection in the North West of England. METHODS: Standard,
      structured questionnaires were used to gather epidemiological information from
      cases of campylobacter infection in the North West Region of England between 1997
      and 1999. The strains of campylobacter isolated from these cases were identified
      and typed using serotyping and phage typing methods. Analysis of combined
      serotype and epidemiological data is presented. RESULTS AND CONCLUSIONS: Human
      campylobacter infection in the North West is seasonal and a new observation was a
      peak in cases in March each year. Drinking bird-pecked milk was a highly seasonal
      exposure that might be an indicator of environmental contamination with
      campylobacter. A possible environmental basis for seasonality of infection is
      discussed. Frequencies of risk exposures related to serotypes of cases are
      described and a potential association was demonstrated between Campylobacter
      jejuni HS6 and consumption of bird-pecked milk. Also, Campylobacter coli
      infections were more commonly associated with travel abroad than C. jejuni and a
      decreased proportion of C. jejuni HS2 and C. jejuni HS11 reported consumption of
      meat and unpasteurised milk (respectively). Contact with a sick animal may be a
      significant risk exposure in younger age groups and in those who do not consume
      poultry or meat. It is clear from this and other studies that the sources and
      vehicles of human campylobacter infection are numerous and interventions that
      target a single risk factor are unlikely to impact significantly on the overall
      burden of disease.

PMID- 12504608
TI  - Changing socioeconomic risk factors for invasive H. influenzae disease after the
      introduction of conjugate vaccine.
AB  - OBJECTIVES: To determine socioeconomic risk factors for invasive Haemophilus
      influenzae (HI) disease before and after the introduction of HI type b (Hib)
      conjugate vaccine in the West Midlands, UK. METHODS: Study population consisted
      of children aged <5 years with laboratory confirmed invasive disease. Linear
      associations between disease rates and socioeconomic variables were examined 2
      years before and 2-years after the introduction of conjugate vaccine. RESULTS:
      Pre-vaccine there were no trends in disease incidence. Post-vaccine there was an
      absolute reduction in disease incidence and significant disease differentials
      between affluent and deprived populations were identified for non-owner-occupancy
      (P=0.032) and car access (P=0.049). CONCLUSIONS: Our results suggest that changes
      in socioeconomic risk factor for invasive HI occurred after the introduction of
      conjugate vaccine. This may have implications for future immunisation strategies.

PMID- 12504609
TI  - Plural transformation-processes from spiral to coccoid Helicobacter pylori and
      its viability.
AB  - OBJECTIVES: Helicobacter pylori (H. pylori), present in a half of the world's
      population, is a very successful pathogen. The infection by this bacterium causes
      several gastric diseases in human. H. pylori is morphologically divided into two
      types; a spiral and a coccoid form. Both types are observed in human stomach.
      Although the former is converted into the latter in vitro, the process of coccoid
      formation remains obscure. Furthermore, whether coccoid forms possess viability
      arouses much controversy among scientists. We investigated both the process of
      coccoid formation by electron microscopy and the viability of coccoid H. pylori.
      METHODS: A laboratory strain, ATCC43504, was cultured in liquid medium (Brucella
      Broth medium with 10% heat inactivated horse serum) for seven days. In each
      culture day, the organisms were observed by scanning-, conventional transmission-
      and immuno-electron microscopy and were simultaneously examined the culturability
      of H. pylori to identify the viability of coccoid form. RESULTS: As the days went
      by, spiral forms were replaced by coccoid forms in each medium which possessed
      culturability to some degree until the 4th day. By the detailed observation of
      ultrastructural features, coccoid forms were classified into two types on the
      ground that represents different transformation-processes and distinctive
      ultrastructures. One was the coccoid form that we named Type A with an
      irregularly surface- and intracytoplasmic-structure which adhered to one another.
      The other was Type B having a smooth surface with flagella coiled around its own
      body and the strictly membranous structure. This type was not adhered to another
      organism. In later days, each type came to be similar external structure and lost
      the culturability. CONCLUSIONS: The coccoid forms of H. pylori can be classified
      into two types by electron microscopy which represent different transformation
      processes and consist of the dying bacteria, the living ones with culturability
      and the viable but non-culturable ones.

PMID- 12504610
TI  - A comparison of pulmonary exacerbations with single and multiple organisms in
      patients with cystic fibrosis and chronic Burkholderia cepacia infection.
AB  - STUDY OBJECTIVES: To compare pulmonary exacerbations with single and multiple
      organisms in patients with chronic Burkholderia cepacia infection. DESIGN: Data
      was collected over a 23-month period and for each of the patients two episodes of
      pulmonary exacerbation were identified, one with B. cepacia isolated as the sole
      respiratory pathogen and the other with one or more coinfecting organisms grown
      from the sputum culture. SETTING: Regional tertiary referral center for
      Respiratory Medicine and Adult Cystic Fibrosis Center for Northern Ireland,
      Belfast City Hospital. PATIENTS: Adult (over 16 years) CF patients with chronic
      (more than 4 years) B. cepacia complex infection who attended the Belfast City
      Hospital between January 1997 and November 1998. MEASUREMENTS: Forced expiratory
      volume in 1s, forced vital capacity, forced expiratory flow rate 25-75, C
      reactive protein, leucocyte count and body mass index were measured before and
      after two weeks of treatment and analysed for any differences in change between
      the two episodes. RESULTS: All variables in both groups improved following
      treatment except for body mass index, which remained unchanged. No significant
      differences between the measurements were identified on comparison of single
      (monomicrobial) and multiple (polymicrobial) isolate episodes. CONCLUSION:
      Patients with chronic B. cepacia infection who develop a pulmonary exacerbation
      improve, as reflected by clinical and biochemical markers, following IV
      antibiotic treatment. Pulmonary exacerbations with multiple organisms are no more
      severe than those where only B. cepacia is isolated.

PMID- 12504611
TI  - Mycobacterium malmoense septic arthritis.
AB  - We report a case of septic arthritis of an interphalangeal joint and
      osteomyelitis of the phalanx due toMycobacterium malmoense in a 61-year-old man
      with a 20 year history of rheumatoid arthritis treated with steroids and
      azathioprine. This was successfully treated with ethambutol, rifampicin and
      clarithromycin. To our knowledge this is the only reported case of septic
      arthritis due to this pathogen which is usually associated with respiratory
      disease or cervical lymphadenitis.

PMID- 12504612
TI  - Brevibacterium casei bacteremia and line sepsis in a patient with AIDS.
AB  - Brevibacteria are obligately aerobic gram-positive bacilli that are associated
      with milk products and are also found on human skin. Strains of Brevibacterium
      casei have been found to correspond to Centers for Disease Control coryneform
      groups B-1 and B-3 and have been isolated from a variety of human clinical
      specimens. In this report, we describe a case of B. casei bacteremia and sepsis
      in a patient with AIDS associated with a contaminated Hickmann catheter and
      review the microbiology and characteristics of these emerging opportunistic
      pathogens.

PMID- 12504613
TI  - Granulomatous peritonitis in hydatid disease.
AB  - We report a rare case of persisting granulomatous inflammation within the
      peritoneal cavity due to previous leakage from a liver hydatid cyst, with the
      granulomata bearing hooklets originating from protosolices of Echinococcus
      granulosus. The patient was treated with a full three-month course of
      albendazole. We believe this represents a rare case of 'pseudotuberculous
      peritonitis'.

PMID- 12504614
TI  - Gingivitis and toothbrushes: potential roles in viridans streptococcal
      bacteraemia.
AB  - We report a case of Streptococcus oralis bacteraemia in a paediatric neutropenic
      patient with acute myeloid leukaemia whose predominant form of oral compromise
      was severe gingivitis, rather than mucositis. By phenotypic and genotypic
      analyses, the strain of S. oralis from blood culture was indistinguishable from
      an isolate from his mouth, suggesting that gingivitis may have provided a portal
      of entry for viridans streptococci into the bloodstream. To improve the patient's
      oral and dental hygiene and reduce gingivitis, conventional disposable foam
      toothettes were substituted with a new soft toothbrush for use as part of the
      oral care protocol. As there are no guidelines regarding the frequency of
      replacement of toothbrushes used by immunocompromised patients, the brush was
      swabbed regularly and culture performed to detect microbial colonization.
      Viridans streptococci were cultured from the toothbrush after 2 weeks of use.
      Phenotypic, followed by genotypic analyses, demonstrated that a strain of S.
      oralis from the toothbrush was indistinguishable from the strain previously
      isolated from blood culture and mouth. Soft toothbrushes may be useful tools for
      maintaining oral hygiene in immunocompromised individuals. However the results of
      this study indicate that regular replacement is warranted, as the toothbrush
      itself may become colonized with the organisms responsible for bacteraemia.

PMID- 12504615
TI  - Listeria monocytogenes meningitis in a patient with chronic hepatitis C
      infection, treated by interferon alfa and ribavirin.
AB  - We present a patient with chronic hepatitis C infection without cirrhosis,
      treated by interferon alfa and ribavirin, who developed listeria monocytogenes
      meningitis. The possible pathophysiological association is discussed, along with
      therapeutic implications.

PMID- 12504616
TI  - Is there a need for taking blood cultures from febrile adults discharged from the
      emergency department?

PMID- 12504617
TI  - Seroprevalence of toxoplasma antibodies among patients with ocular disease in
      Slovenia.

PMID- 12504618
TI  - High-dose chemotherapy in ovarian cancer: still waiting for the right study.

PMID- 12504619
TI  - Pilot evaluation of high-dose carboplatin and paclitaxel followed by high-dose
      melphalan supported by peripheral blood stem cells in previously untreated
      advanced ovarian cancer: a gynecologic oncology group study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of multiple cycles of high-dose
      carboplatin and paclitaxel and one consolidation cycle of high-dose melphalan
      with all cycles supported by hematopoietic stem cells and cytokine, in previously
      untreated patients with optimally debulked stage III epithelial ovarian cancer.
      PATIENTS AND METHOD: Patients had histologically documented epithelial ovarian
      cancer and optimal initial cytoreductive surgery. No prior chemotherapy was
      permitted. Adequate performance status, bone marrow, hepatic, and renal function
      was required. After being mobilized with cyclophosphamide 3 g/m(2), paclitaxel
      300 mg/m(2), and filgrastim 5 microg/kg/day, peripheral blood stem cells (PBSC)
      were collected by leukapheresis. Patients received three cycles of carboplatin
      AUC 15 mg. min/ml iv, paclitaxel 250 mg/m(2), and PBSC with filgrastim every 28
      days, followed by one cycle of melphalan 140 mg/m(2) and hematopoietic support.
      RESULTS: Nine patients entered the trial and received all planned cycles of
      chemotherapy. Of the eight patients who consented to surgical reassessment upon
      completing therapy, four had residual small-volume macroscopic disease, three had
      microscopic residual disease, and one had pathologic complete response. The
      estimated probability of a pathologic complete response was 12.5% (95% confidence
      interval: 0.3-52.7%). Hematologic toxicity was severe but manageable. Eleven of
      45 cycles (24.4%) resulted in hospital admission for neutropenic fever,
      dehydration +/- diarrhea, syncope, or shortness of breath and pain secondary to
      tense ascites. CONCLUSIONS: The low pathological complete response rate did not
      justify toxicity; thus, the study was closed. High-dose chemotherapy as first
      line treatment for epithelial ovarian cancer remains experimental and should be
      restricted to clinical trials.

PMID- 12504620
TI  - Quality of life in women treated with neoadjuvant chemotherapy for advanced
      ovarian cancer: a prospective longitudinal study.
AB  - OBJECTIVE: The purpose was to examine the outcomes of patients with advanced
      ovarian cancer treated with neoadjuvant chemotherapy, with a special emphasis on
      the patients' quality of life (QOL). METHODS: Seventeen patients with advanced
      ovarian cancer were treated with neoadjuvant chemotherapy based on the extent of
      disease on computer tomography. All patients received combined
      platinum/paclitaxel chemotherapy. Debulking surgery was performed after three
      cycles or six cycles of chemotherapy, depending on the response to the
      chemotherapy. Patients' QOL was studied over time using European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire C30 and was then
      compared with that of patients treated with conventional treatment in the
      previous cohort. RESULTS: The response rate to chemotherapy assessed at three
      cycles was 82.4%. The rate of optimum debulking to residual disease less than 2
      cm after chemotherapy was 76.9%, and 38.5% had no gross residual disease after
      surgery. The median overall survival was 22.9 months. The median disease-free
      interval was 13.3 months. The overall QOL improved after chemotherapy and this
      continued to improve up to 12 months. The other functional scales also showed
      improvements over time, apart from the initial transient deterioration in the
      role functioning and cognitive functioning at 3 months after chemotherapy.
      Patients treated with neoadjuvant chemotherapy seem to have better but
      statistically insignificant difference in QOL parameters than patients treated
      conventionally. CONCLUSION: Neoadjuvant chemotherapy is an alternative treatment
      for patients with advanced ovarian cancer in whom the chance of optimal
      cytoreduction is low. The patients' overall quality of life and functional status
      improve after neoadjuvant chemotherapy.

PMID- 12504621
TI  - Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum-
      and multidrug-resistant ovarian and peritoneal carcinoma.
AB  - OBJECTIVE: Preclinical models in an ovarian cancer cell line (A2780) demonstrate
      synergistic activity with the combination of gemcitabine and cisplatin compared
      to either single agent alone. Platinum resistance is related to expression of
      excision repair proteins, one of which (ERCC-1) has been identified as playing a
      critical role in the synergy of gemcitabine and cisplatin. We evaluated the
      cisplatin and gemcitabine regimen in patients with platinum refractory and
      multidrug refractory ovarian and peritoneal carcinoma. METHODS: Gemcitabine (750
      mg/m(2)) was administered intravenously over 30 min followed by cisplatin (30
      mg/m(2)) on Days 1 and 8 every 21 days. Day 8 therapy was canceled for an
      absolute neutrophil count <1000/mm(3) or platelet count <75,000/mm(3). Sequential
      dose reductions of gemcitabine to 600, 400, and 300 mg/m(2) were prescribed in
      the event of canceled therapy, neutropenic sepsis, or severe thrombocytopenia
      (platelets <20,000/m(3)). RESULTS: Thirty-six platinum- and paclitaxel-resistant
      patients were studied. Thirty-five were evaluable for response, of which 6 had
      progressed on gemcitabine as a single agent. Fifteen of the patients responded
      (42.9%, 95% CI 28.0-59.1%). Eleven were partial clinical responses and 4 were
      complete clinical responses, with 4 of the 6 patients who had failed gemcitabine
      as a single agent responding. Among the responding patients the median response
      duration was 11 months (range 4-14 months). For all patients the progression-free
      interval was 6 months (range 1-14 months). The median survival was 12 months.
      CONCLUSION: The combination of gemcitabine and cisplatin is active in patients
      who are platinum resistant. Additionally, activity is demonstrated even in
      patients who have previously been resistant to gemcitabine.

PMID- 12504622
TI  - Evaluation of p53 and Bcl-2 expression as prognostic markers in invasive cervical
      carcinoma stage IIb/III patients treated by radiotherapy.
AB  - OBJECTIVE: The objective was to evaluate the immunohistochemical expression of
      p53 and Bcl-2 proteins as prognostic markers in locally advanced [FIGO Stage
      IIb/III] invasive squamous cell carcinoma of the uterine cervix. It was also our
      aim to determine if they had any relationship to each other and to the
      pretreatment levels of apoptosis determined morphologically. METHODS: Seventy-six
      consecutive cases of invasive squamous cell carcinoma of the cervix diagnosed in
      1995 were analyzed retrospectively for the apoptotic index and p53 and Bcl-2
      expression determined immunohistochemically and correlated to the patient outcome
      at the end of a 5-year follow-up period. RESULTS: The overall cumulative 5-year
      survival was 52.63%. p53 immunoreactivity was seen in 53.9% cases with variable
      levels of expression. By univariate analysis, p53 positivity correlated with poor
      survival [chi-square P = 0.029; log-rank test P = 0.0468] but not upon
      multivariate analysis. The apoptotic index which ranged from 0 to 40 and Bcl-2
      expression seen in 38.1% cases showed no correlation to survival. Neither p53 nor
      Bcl-2 expression correlated with the apoptotic index or with each other. Seven
      cases with the immunophenotype p53-/Bcl-2+ had an excellent survival.
      CONCLUSIONS: Neither p53 nor Bcl-2 expression are independent predictors of
      prognosis in locally advanced cervical squamous cancers. However, evaluation of
      their combined expression may affect clinical outcome and needs further
      investigation.

PMID- 12504623
TI  - Further data on the usefulness of sentinel lymph node identification and
      ultrastaging in vulvar squamous cell carcinoma.
AB  - OBJECTIVE: The aim was to determine the feasibility of surgical identification
      and pathological ultrastaging of sentinel nodes (SNs) in vulvar carcinoma and to
      evaluate whether SN negativity rules out the possibility of metastasis in other
      nodes and can therefore avoid conventional lymphadenectomy. MATERIAL AND METHODS:
      In 26 patients with vulvar squamous cell carcinoma the SNs were detected using
      both peritumoral injection of (99m)Tc and blue dye (isosulfan or methylene)
      before the surgical procedure. Dissection of the SNs was followed by standard
      lymphadenectomy and vulvar exeresis. For pathological ultrastaging at least eight
      histological sections of every node separated 400 microm were evaluated using
      hematoxylin & eosin and immunostaining against cytokeratin. RESULTS: We
      identified the SNs in 25/26 patients (96%). In 19 patients (76%) the SN was
      unilateral and in 6 (24%) it was bilateral. A total of 46 SNs were isolated.
      Metastatic carcinoma was identified in 9 SNs from 8 patients (30.8%). Thirty
      eight percent (3 of 8) patients with metastatic SNs presented micrometastasis
      detected only in ultrastaging. Seven (3.3%) of 239 nonsentinel nodes (non-SNs)
      showed metastasis. No metastatic implant was detected in non-SNs when SNs were
      negative in patients without clinical suspicious adenopathy (100% negative
      predictive value). CONCLUSION: Inguinofemoral lymph nodes can be confidently
      avoided when sentinel node metastases are excluded by histological ultrastaging.
      This may reduce the surgical morbidity of conventional inguinofemoral
      lymphadenectomy, without worsening vulvar cancer prognosis.

PMID- 12504624
TI  - Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in
      previously treated, relapsed ovarian cancer patients.
AB  - OBJECTIVES: The aim was to determine the safety and efficacy of gemcitabine plus
      cisplatin for patients with relapsed ovarian carcinoma and to compare ex vivo
      drug sensitivity profiles with clinical outcomes. PATIENTS AND METHODS:
      Previously treated patients with ovarian carcinoma received cisplatin (30
      mg/m(2)) plus gemcitabine (600-750 mg/m(2)) on Days 1 and 8 of each 21-day cycle.
      Seventeen of the 27 patients underwent ex vivo analyses for correlation with
      clinical response. RESULTS: Of 27 patients, there were 7 (26%) complete and 12
      (44%) partial responses, for an overall response rate of 70% (95% CI: 53-87%).
      Toxicities included neutropenia Grade III in 51.9%, Grade IV in 29.6%; anemia
      Grade III in 18.5 %; thrombocytopenia Grade III in 66.7 %, Grade IV in 29.6%;
      nausea and vomiting Grade III in 14.8 %; peripheral neuropathy Grade III in 3.7%;
      and alopecia Grade IV in 11.1% of patients. The median time to progression for
      objective responders was 7.9 months with a range of 2.1 to 13.2 months. There
      were no treatment-related deaths. Ex vivo results correlated with response, time
      to progression, and survival, remaining significant when adjusted for platin
      resistance and number of prior therapies. Adjustment for platin-free interval
      decreased the significance but did not, in and of itself, predict significantly
      for progression-free survival. CONCLUSIONS: Cisplatin plus gemcitabine is active
      for patients with relapsed ovarian cancer. Toxicities, primarily hematologic, are
      manageable with dose modifications. Responses observed in heavily pretreated and
      platin-resistant patients indicate activity in drug-refractory patients. The
      results of the ex vivo analyses correlate with clinical outcomes.

PMID- 12504625
TI  - Evaluation of p27 in preinvasive and invasive malignancies of the cervix.
AB  - OBJECTIVE: p27 is a cell cycle inhibitor whose loss is commonly found in
      epithelial tumors. Low levels have been associated with poor prognosis. Our goal
      was to determine if p27 expression could be used to screen for dysplasia and if
      it is a prognostic factor for cervical malignancies. METHODS: Ten normal
      cervices, 51 consecutive cone biopsies for preinvasive disease, and 128
      consecutive hysterectomies for invasive cervical cancer (1994-1999) were stained
      for p27 using standard immunocytochemical techniques. All of the cervical cancer
      patients were managed with radical hysterectomy and lymph node dissection, except
      for 14 women who underwent adjuvant hysterectomy and lymph node sampling after
      chemoradiation. RESULTS: There was no significant difference in p27 staining
      between normal cervices (all stained 4+) and preinvasive lesions (46/51 stained
      4+ and 5/51 stained 3+). For the invasive lesions, 47 women had no residual
      disease in the hysterectomy specimen, due to prior cone biopsy (41) or radiation
      (6). All had 4+ p27 staining in the residual cervix. None of these women
      recurred. Eighty-one women had residual disease in the hysterectomy specimen;
      25/81 (31%) had p27 staining of <50%. Loss of p27 was not significantly
      associated with invasion >50% (32 vs 27%), size >4 cm (20 vs 13%), or use of
      postoperative radiation (36 vs 20%). Loss of p27 was associated with
      lymphvascular space invasion (LVSI) (44 vs 20%, P = 0.04). Only 4 women had nodal
      metastasis; all 4 had p27 staining less than 50%; 6/81 (7%) women with residual
      disease developed recurrences and died. Of the women who died, 3/6 had p27
      staining less than 50%. CONCLUSION: p27 is not lost in preinvasive cervical
      lesions and, therefore, cannot be used to screen for dysplasia. In cervical
      cancers p27 staining was <50% in 31% of cases, and is associated with increased
      risk of LVSI. Perhaps, because of the excellent overall survival of this group of
      women with Stage I cervical cancer, loss of p27 staining was not associated with
      poor prognosis.

PMID- 12504626
TI  - Mucosal melanoma of the female genital tract is a multifocal disorder.
AB  - OBJECTIVE: This is a retrospective analysis of malignant melanoma of the female
      genital tract, focusing on the high local recurrence rate of this tumor. METHODS:
      All women treated for malignant melanoma of the genital tract were identified
      through the archives of the Hadassah University Hospital. The medical records and
      the pathological specimens were reviewed and reevaluated. RESULTS: From 1986 to
      2002, nine cases were diagnosed and treated at Hadassah. Seven had vulvar
      melanoma and two had vaginal melanoma. Sixty-six percent (6/9) of the patients
      had more than one focus of melanoma, either apparent at their initial diagnosis
      (3/9) or developed during follow up (3/9). Most of the recurring lesions were
      melanoma in situ. In one patient multiple nodular melanomas were detected.
      Atypical melanocytic hyperplasia was found in an otherwise normal mucosa in four
      patients. Three had experienced multiple recurrences. All patients were treated
      by radical local excisions with (3/9) or without (6/9) elective groin lymph node
      dissection. Three patients with locally recurring melanoma within the genital
      tract required two to five sessions of repeated surgical excisions. CONCLUSION:
      It is suggested that melanoma of the genital tract is the result of a multifocal
      disorder of the melanocytes within the mucosa. The increased local recurrence
      rate reflects an inherent abnormality of melanocytes. It is not attributed to
      surgical failure in controlling the disease. Insistent and even radical surgical
      excision is recommended, especially for patients whose prospects for prolonged
      survival are improved.

PMID- 12504627
TI  - Weekly low-dose carboplatin and paclitaxel in the treatment of recurrent ovarian
      and peritoneal cancer.
AB  - OBJECTIVES: Weekly paclitaxel alone has moderate activity in the salvage
      treatment of recurrent ovarian cancer and is associated with a favorable toxicity
      profile. Combination paclitaxel and carboplatin is a well-established first-line
      regimen for ovarian cancer. The purpose of this study was to evaluate weekly low
      dose paclitaxel and carboplatin in recurrent ovarian or peritoneal cancer.
      METHODS: Patients with recurrent ovarian or peritoneal cancer previously treated
      with between one and four chemotherapeutic regimens were eligible. Patients had
      measurable or assessable disease defined by clinical exam, radiographic studies,
      or serum CA-125 greater than 75 U/ml. One cycle of treatment consisted of
      carboplatin at an area under the curve of 2 and paclitaxel at 80 mg/m(2) on days
      1, 8, and 15 on a 28-day cycle. Clinical responses were defined by established
      criteria. RESULTS: Twenty-nine patients were included in this intent-to-treat
      study. The median number of prior treatment regimens was 2 (range 1 to 4). The
      overall response rate was 82.8% (16 complete clinical responses, 8 partial
      responses). Among 8 platinum-refractory patients, the response rate was 37.5%,
      while 21 platinum-sensitive patients had a 100% response rate. Median time to
      progression was 13.7 months among platinum-sensitive patients and 3.2 months
      among platinum-refractory patients. Overall median time to progression was 11.5
      months and median-duration of response was 9.9 months. Hematologic toxicity was
      common (32% grade 3 neutropenia, no grade 4 neutropenia, 14.2% grade 3 or 4
      thrombocytopenia) and managed by treatment delay, dose reduction of paclitaxel,
      or discontinuation of carboplatin. CONCLUSION: Weekly low-dose carboplatin and
      paclitaxel has significant activity in both platinum-sensitive and platinum
      resistant recurrent ovarian cancer with acceptable toxicity that is easily
      managed by dose adjustment.

PMID- 12504628
TI  - Frequency of BRCA mutations in primary peritoneal carcinoma in Israeli Jewish
      women.
AB  - OBJECTIVE: The aim of the present study was to compare demographic and clinical
      characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC)
      with regard to BRCA mutation frequencies. METHODS: Incident cases of
      histologically confirmed cancer of the ovary or peritoneum diagnosed in Israeli
      Jewish women between March 1, 1994, and June 30, 1999, were identified within the
      framework of an ongoing nationwide epidemiological study of these neoplasms in
      Israel. The present study comprises 609 (81.5% of 747) Jewish women with
      epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were
      genetically tested for the BRCA mutations. Data from each patient were collected
      by the aid of a prestructured questionnaire and medical records. Blood samples or
      tumor tissue was tested for the 185delAG and 5382insC mutations in BRCA1 and the
      6174delT mutations in BRCA2. RESULTS: A carrier rate of 28% of any BRCA 1/2
      mutation was observed among the PPC group and of 30% among the invasive stage III
      IV OvC. No differences were found between PPC and OvC neither in the overall
      distribution of BRCA1/2 mutation carrier rates nor according to type of mutation,
      age, ethnic origin, and histologic subtype. Among women with a positive family
      history, a higher rate of mutation carriers was observed in the PPC group
      compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07). CONCLUSIONS:
      The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed
      in the present study indicates that these mutations may predispose to PPC as well
      and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome.

PMID- 12504629
TI  - Vaginal cuff recurrence of endometrial cancer treated by laparoscopic-assisted
      vaginal hysterectomy.
AB  - BACKGROUND: Laparoscopic-assisted vaginal hysterectomy (LAVH) has been suggested
      as an alternative to total abdominal hysterectomy (TAH) for the treatment of
      early endometrial cancer. Although studies have reported good results with
      equivalent rates of recurrence and survival, the need for use of intrauterine
      manipulators during the LAVH raises the concern for operative dissemination of
      tumor cells. CASES: We report three patients with stage I, noninvasive or
      superficially invasive endometrial cancer with vaginal cuff recurrence within 9
      months of treatment by LAVH. CONCLUSION: While LAVH may be a technically
      acceptable alternative to TAH for the management of early-stage endometrial
      cancer, its routine use should be undertaken with caution, as the long-term risks
      for recurrence and survival have yet to be defined in a randomized, controlled
      fashion.

PMID- 12504630
TI  - Synchronous renal cell carcinoma and gynecologic malignancies.
AB  - BACKGROUND: Synchronicity of renal cell carcinoma and gynecologic malignancies is
      a rare condition and standardized treatment does not exist. CASES: Three cases of
      synchronous renal cell carcinoma and gynecologic malignancies are described. All
      three cases underwent optimal cytoreductive surgery for the gynecologic
      malignancy and a radical nephrectomy for the renal cell carcinoma. Adjuvant
      treatment, after surgery, was individualized in each case. Estrogen and
      progesterone receptors were positive in all the gynecologic tumors but negative
      in the renal cell tumors. CONCLUSIONS: This is apparently the largest report of
      synchronous renal cell carcinoma and gynecologic malignancies. Despite this rare
      condition, surgery should still be considered as primary treatment for these
      patients.

PMID- 12504631
TI  - Successful term pregnancy after selective arterial embolization of symptomatic
      arteriovenous malformation in the setting of gestational trophoblastic tumor.
AB  - BACKGROUND: Patients with arteriovenous malformations (AVMs) are at risk for
      significant vaginal hemorrhage, and are traditionally managed surgically. In the
      patient desiring future fertility, conservative management via selective arterial
      embolization is a reasonable option. Only a few cases have been previously
      reported of successful pregnancy after this procedure in the setting of
      gestational trophoblastic disease (GTD). CASE: A 31-year-old gravida 1 para 0 was
      treated for persistent gestational trophoblastic tumor after a complete mole in
      1997. She presented with heavy vaginal bleeding, and arteriogram demonstrated a
      large uterine AVM. The patient underwent selective uterine artery embolization
      with complete resolution of bleeding, as well as arteriographic cessation of flow
      through the AVM. After two first-trimester spontaneous abortions, the patient
      successfully completed a normal pregnancy, resulting in the forceps-assisted
      delivery of a healthy female infant. CONCLUSION: Successful term pregnancy can
      occur after selective uterine artery embolization in women hemorrhaging from
      symptomatic GTD-associated AVM.

PMID- 12504632
TI  - Activated SRC protein tyrosine kinase is overexpressed in late-stage human
      ovarian cancers.
AB  - OBJECTIVE: The objective of this study was to determine if the Src tyrosine
      kinase is overexpressed and activated in late-stage human ovarian cancers.
      METHODS: Western analysis and immune complex kinase assays were performed on a
      panel of human ovarian cancer cell lines and normal ovarian epithelial cell
      cultures, and immunohistochemical analysis for Src and activated Src were
      performed on a panel of late-stage human ovarian tumors. RESULTS AND CONCLUSIONS:
      Src is overexpressed and activated in a majority of late-stage ovarian tumors as
      well as in a panel of cultured malignant human ovarian epithelium grown in vitro,
      but not in normal ovarian epithelium (NOE) or immortalized NOE. Src
      overexpression was found to be frequently, but not always, associated with HER
      2/neu overexpression, but no statistical association between Src and Her-2/neu
      overexpression could be demonstrated.

PMID- 12504633
TI  - Reduction of blood loss during extensive pelvic procedures by aortic clamping--a
      preliminary report.
AB  - OBJECTIVE: The aim was to determine the effect of intraoperative aortic clamping
      during extensive pelvic procedures on blood loss, operative time, and morbidity.
      METHODS AND MATERIALS: Thirteen women with ovarian cancer, 1 with cervical
      cancer, and 1 with an extensive pelvic sarcoma had their aortas completely
      occluded with a vascular clamp before the pelvic phases of their operations.
      Heparin and protamine reversal were used. RESULTS: Patients requiring en bloc
      excision of the internal reproductive organs, pelvic peritoneum, and recto
      sigmoid colon in the context of a cytoreductive operation had a median estimated
      total blood loss of 650 ml (range 200 to 3500), a median of 2 units (range 0 to
      8) of blood transfused, and a median total operative time of 155 min (range 90 to
      280). There were no complications due to the aortic clamping. CONCLUSION: Most
      procedures were completed with a less than anticipated blood loss and operative
      time. Clamping of the aorta may potentially diminish blood loss, operative time,
      and the incidence of transfusion-related morbidity associated with extensive
      pelvic operations. Intraoperative aortic clamping merits further investigation.

PMID- 12504634
TI  - Initiating mechanisms of paroxysmal atrial fibrillation.
AB  - BACKGROUND: The understanding of the onset mechanisms of paroxysmal atrial
      fibrillation (AF) may help to develop preventive therapy. Specific heart rate
      (HR) patterns and autonomic changes immediately before the onset of paroxysmal AF
      are not fully investigated. We undertook the present study to assess HR and heart
      rate variability (HRV) changes before the onset of AF using 24-h Holter
      electrocardiographic analysis in patients without antiarrhythmic medication.
      METHODS AND RESULTS: In 27 patients, 48 episodes of AF, lasting more than 30s and
      preceded by sinus rhythm for more than 1h were analysed. The hour preceding AF
      was divided in 5- and 30 min blocks. HR was also analysed in the last 15 beats.
      In 21% of the episodes, HR decreased >or=5% in the last 5 min (defined as
      deceleration); it increased >or=5% in 37% (defined as acceleration). HR, standard
      deviation (SD) and SD corrected for RR interval changed significantly in the last
      5 min in the total group. Acceleration and deceleration were already visible over
      30-min blocks in both these subgroups; changes in SD were only seen in the
      accelerators. The number of atrial premature beats (PACs) increased before AF,
      most clearly in the accelerators. Spectral HRV analysis revealed no additional
      information. CONCLUSIONS: Changes in HR, SD, and an increased number of PACs
      herald AF from at least 30 min before onset, more pronounced in accelerators.
      Spectral HRV parameters are not useful to foresee AF onset. This has possible
      implications for device therapy.

PMID- 12504635
TI  - Long-short sequence may predict immediate recurrence of atrial fibrillation after
      external cardioversion.
AB  - AIM: We thought, that analysis of surface electrocardiograms recorded immediately
      after electrical external cardioversion (EC) might enlighten the mechanisms
      responsible for immediate recurrence of atrial fibrillation (AF) and especially
      to test whether atrial ectopic beats (PAC) with long-short (LS) sequence are
      related to the recurrence of arrhythmia after cardioversion in patients with
      chronic AF. METHODS AND RESULTS: One hundred and thirty-seven patients (mean age
      57+/-7 years) undergoing EC for chronic AF entered the study. Evaluation of the
      patients included clinical history, physical examination, ECG, routine laboratory
      tests, and transthoracic echocardiography. The cardioversion was performed with
      monophasic waveform shock and immediately after successful EC, 1 min of recording
      of the ECG lead II was analysed. One hundred and twenty patients (87%) of 137
      patients enrolled in the study had had successful EC and 33 (27%) of them
      experienced immediate recurrence of AF within 1 min (Group I) and 87 patients had
      no arrhythmia recurrence (Group II). In group I in 24 patients (73%) recurrence
      of AF was initiated by PAC with LS sequence. In only 12 of 87 (13%) patients who
      did not experience immediate recurrence of AF (Group II) PACs were recorded.
      CONCLUSIONS: Atrial ectopic beats (PACs) with LS sequence, being responsible for
      AF relapse in about 70% of patients, might predict early re-initiation of
      arrhythmia after EC. Electrocardiograms, recorded immediately after EC, are a
      potentially feasible approach in establishing the patterns of AF relapse that may
      be useful in the management of AF recurrence.

PMID- 12504636
TI  - Relationship between the frequency of paroxysmal episodes of atrial fibrillation
      and pulmonary venous flow pattern.
AB  - AIMS: Chronic atrial fibrillation causes mechanical remodelling of the atria, but
      it is uncertain whether self-terminating episodes of paroxysmal atrial
      fibrillation (PAF) alter atrial mechanical function during normal sinus rhythm.
      This study was designed to assess the relationship between the frequency of
      symptomatic arrhythmic episodes and pulmonary venous flow (PVF) pattern among
      patients with PAF. METHODS AND RESULTS: The effect of symptomatic arrhythmic
      episodes on PVF was studied in 85 patients with lone PAF (age 48+/-8 years, 66
      men). PVF was measured with transthoracic echocardiography during sinus rhythm.
      Adequate recordings of PVF were achieved in 81 (95%) patients. Peak systolic PVF
      had an inverse correlation (r=-0.35, P=0.002) with the frequency of PAF episodes.
      The peak systolic PVF was 76+/-14 cm/s vs 62+/-12 cm/s (P=0.008) among the
      quartiles with the most and the least frequent episodes of PAF, respectively.
      There were no significant differences in the other echocardiographic measurements
      or demographic variables. CONCLUSIONS: Frequent arrhythmic episodes significantly
      diminished systolic PVF among patients with PAF, suggesting that PAF results in
      gradual mechanical remodelling of the atrium, which may favour recurrence and
      perpetuation of AF and/or formation of atrial thrombus.

PMID- 12504637
TI  - Effect of atrial overdrive pacing on pulmonary vein focal discharge in patients
      with atrial fibrillation.
AB  - AIMS: Recently, it has been shown that atrial fibrillation may be caused by
      spontaneously discharging foci located predominantly in the pulmonary veins.
      However, the effect of atrial overdrive pacing on these pulmonary vein foci has
      not been studied. METHODS AND RESULTS: In 58 patients with drug refractory
      paroxysmal or persistent atrial fibrillation we performed radiofrequency catheter
      ablation of arrhythmogenic triggers inside the pulmonary veins and/or an ostial
      pulmonary vein isolation with conventional mapping and ablation technology.
      Continuous bigeminal pattern of discharge from one or more arrhythmogenic
      pulmonary veins was recorded in 14 patients. Atrial overdrive pacing resulted in
      suppression of pulmonary vein 'focus' activity in all patients. The longest mean
      atrial pacing cycle length resulting in overdrive suppression was 587+/-114 ms.
      Independent of pacing rate and duration, bigeminal pulmonary vein focus activity
      reemerged 2.5+/-3.7s after cessation of pacing. Overdrive suppression of the
      pulmonary vein focus was incomplete in 9 pacing attempts, and resulted in
      induction of atrial fibrillation from the same vein in 3 of 31 pacing manoeuvres.
      At 2 years follow-up 79% of these patients were free of atrial fibrillation, 55%
      without antiarrhythmic drugs, 24% on previously ineffective antiarrhythmic drug
      therapy. CONCLUSION: Stable pulmonary vein 'focus' activity in patients with
      atrial fibrillation can be suppressed by atrial overdrive pacing. However,
      'proarrhythmic' effects of atrial overdrive pacing, such as induction of atrial
      fibrillation, were also seen.

PMID- 12504638
TI  - The effect of endocardial defibrillator shocks on basic atrial electrophysiology
      in man. Is post cardioversion atrial electrical 'remodelling' artefact?
AB  - AIMS: To determine the effect of an endocardial DC shock on the basic
      electrophysiology of the human atrium if delivered in sinus rhythm. METHODS AND
      RESULTS: A 5J endocardial R wave synchronized DC shock was delivered in 10
      patients in stable sinus rhythm during ICD implantation for ventricular
      arrhythmias. There was no prior history of atrial fibrillation. Monophasic action
      potential duration (APD) and atrial effective refractory periods (AERP) were
      evaluated before, 1 min post DC shock, and 15 min post shock. These parameters
      were assessed at basic cycle lengths and at atrial paced cycle lengths of 600 ms
      and 400 ms at two right atrial sites; mid lateral right atrial wall (MRLA) and
      the right atrial appendage (RAA). There were no significant differences in APD
      90, AERP or atrial refractory dispersion at any site or drive cycle length
      before, immediately after or 15 min after shock delivery. CONCLUSIONS: There are
      no significant changes in basic electrophysiological parameters following a DC
      shock delivered in sinus rhythm in patients with no prior history of atrial
      fibrillation. This suggests that atrial electrical remodelling occurs as a result
      of atrial fibrillation and is unrelated to shock artefact.

PMID- 12504639
TI  - Right atrial modification of maze surgery does not affect refractoriness and
      conduction patterns of human lone atrial fibrillation.
AB  - BACKGROUND: Tissue mass and structure are relevant for initiation and persistence
      of fibrillation. Modification of the right atrium during maze surgery may change
      the arrhythmogenic substrate of atrial fibrillation (AF). METHODS AND RESULTS:
      Epicardial mapping was performed in 9 patients undergoing unmodified maze III
      surgery for lone paroxysmal AF. Simultaneous recording of AF on the right and
      left atrium was carried out with two spoon-electrodes each harbouring 64
      terminals. Activation maps of AF were made to study AF wavelet organization. The
      recording position on right and left atria was outside the surgical field and
      remained unchanged before and after surgery. Before surgery, mean right and left
      fibrillatory intervals were 174+/-23 ms, and 175+/-26 ms, respectively, and did
      not differ. After completed right atrial surgery, these fibrillary intervals
      remained unchanged. Mean right and left atrial dispersion of refractoriness
      (expressed as the coefficient of variation) were 4.2+/-0.8 and 5.2+/-3.8 ms. Only
      right atrial dispersion of refractoriness increased significantly after right
      sided surgery. Prior to surgery, activation patterns of the left atrium were more
      complex than that of the right atrium. The left activation patterns became less
      complex afterwards; the right atrial activation patterns did not change.
      CONCLUSION: The right atrial modification of maze III surgery neither affects
      atrial refractoriness during human lone AF nor changes AF wavelet organization.
      Thus, right atrial surgery does not modify the arrhythmogenic substrate of AF.
      These findings may imply that maze surgery can be restricted to the left atrium.

PMID- 12504640
TI  - Long-term follow-up of cardiac rhythm after percutaneous mitral balloon
      valvotomy. Does atrial fibrillation persist?
AB  - AIMS: Little information is available about short-term and none about long-term
      follow-up of cardiac rhythm after percutaneous mitral balloon valvotomy (PTMV).
      METHODS AND RESULTS: We studied the long-term course of the supraventricular
      rhythm in 137 consecutive patients with severe mitral stenosis, who underwent
      PTMV. The rhythm before PTMV was sinus rhythm (SR) in 55% and chronic AF in 45%
      of patients. The mean follow-up time was 3.7+/-2.5 years (n=126). In patients
      with SR before PTMV, SR persisted in 91% of patients at the end of follow-up. In
      patients with chronic AF before PTMV, 84% of these patients were still in chronic
      AF at the end of follow-up, spontaneous conversion to SR did not occur. In 12 of
      14 patients (85%), selected for cardioversion, SR was achieved, by DC
      cardioversion (n=11) or by drugs alone (n=1). After 2 years this outcome
      persisted, but after 4 years only 38% remained in SR. CONCLUSION: Pre-procedural
      SR will persist following PTMV. However in patients with chronic AF PTMV is not
      associated with reversion to SR, suggesting that measures should be undertaken to
      restore sinus rhythm.

PMID- 12504641
TI  - How to approach epicardial ventricular tachycardia: electroanatomical mapping and
      ablation by transpericardial nonsurgical approach.

PMID- 12504642
TI  - Distinction between atrioventricular reciprocating tachycardia and
      atrioventricular node re-entrant tachycardia in the adult population based on P
      wave location; should we reconsider the value of some ECG criteria according to
      gender and age?
AB  - AIMS: Distinction between atrioventricular node re-entrant tachycardia (AVNRT)
      and atrioventricular reciprocating tachycardia (AVRT) is sometimes difficult
      using location of retrograde P waves on ECG. METHODS: P wave location was
      retrospectively determined in 137 anterior slow-fast AVNRT (85%) and 26
      orthodromic AVRT (15%) with narrow QRS occurring in 161 successive patients
      without pre-excitation. Mechanism of arrhythmia was assessed by
      electrophysiological study and confirmed by the efficacy of radiofrequency
      ablation. P waves were classified as invisible, visible after the QRS, or as R'
      in V(1) and/or S in II. Correlations with arrhythmia mechanism were made
      according to gender and age (>or= or <65 years old). RESULTS: Mechanism was
      related to gender but not to age, with a higher proportion of AVNRT in women
      (89/97, 91%) than in men (48/66, 72%) (P=0.001). AVRT presented with visible P
      waves in 26/26 cases (100%) while AVNRT presented with invisible P waves in
      36/137 (27%), R'V(1)/SII in 79/137 (57%) and visible P waves in 22/137 (16%). P
      wave location during AVNRT was related to age but not to gender, with a higher
      proportion of AVNRT with visible P waves in elderly than in younger patients:
      8/27 (29%) vs 14/110 (12%) (P=0.03). Visible P wave during AVNRT was mainly
      caused by a delay in nodal retrograde conduction in 17/22 patients (77%).
      Mechanism of tachycardia with visible P waves was related to gender (AVNRT in
      14/22 women (64%), AVRT in 18/26 men (70%), P =0.02) and to age, although non
      significantly (AVNRT in 8/13 (62%) old vs 14/35 (40%) young patients, P=0.18). A
      visible P wave was predictive of AVNRT in 25% and in 60% of the men and women
      younger than 65 years old, and in 50% and in 71% of older men and women
      respectively (P=0.08 - borderline significance). CONCLUSIONS: Correct distinction
      between anterior slow-fast AVNRT and orthodromic AVRT can be reliably made
      regardless of gender or age in case of R'V(1)/SII or invisible P wave. AVRT as
      the expected mechanism should be reconsidered in the case of visible P waves in
      the elderly and in the female gender in the absence of pre-excitation.

PMID- 12504643
TI  - Catecholamine response during haemodynamically stable upright posture in
      individuals with and without tilt-table induced vasovagal syncope.
AB  - AIM: Changes in circulating catecholamine concentrations during vasovagal faints
      have been the subject of considerable study. However, whether catecholamines are
      part of the triggering mechanism, or principally reflect attempted compensation
      for an evolving circulatory crisis is unknown. To address this issue, we
      determined whether the circulating catecholamine response to upright posture
      differs among patients with and without inducible vasovagal faints at a time when
      there is no detectable haemodynamic compromise. METHODS AND RESULTS: Blood
      samples for measurement of adrenaline and noradrenaline (Norepi) concentrations
      were obtained in the baseline state, and at both 2-3 min and 4-6 min of upright
      posture in 22 patients undergoing head-up tilt-table testing for evaluation of
      syncope of unknown cause. In 11 individuals tilt-testing induced syncope at >5
      min head-up posture (Group 1). In 11 other individuals tilt testing did not
      result in syncope (Group 2). Supine arterial catecholamine levels were comparable
      in the two groups. However, adrenaline concentrations during upright posture
      tended to be greater at 2-3 min and were significantly greater at 4-6 min in
      Group 1 than in Group 2 (P< 0.01). These differences occurred in the absence of
      significant intergroup differences in mean arterial pressure or cardiac cycle
      lengths. Norepi concentrations also increased in both groups, but without
      significant differences. CONCLUSION: Circulating adrenaline concentrations in
      posturally induced vasovagal faints rise more rapidly in vasovagal fainters than
      in comparably posturally stressed non-fainters, and were significantly greater in
      fainters prior to either detectable haemodynamic compromise or diminution of
      circulating Norepi levels. These findings suggest that a premonitory rise in
      adrenaline concentrations occurs in vasovagal fainters unassociated with an
      evolving circulatory crisis.

PMID- 12504644
TI  - Prevention of Syncope Trial (POST): a randomized clinical trial of beta blockers
      in the prevention of vasovagal syncope; rationale and study design.
AB  - BACKGROUND: Few therapies for vasovagal syncope have been proven effective. A
      large, placebo-controlled clinical trial of beta-blockers is needed. STRUCTURE OF
      STUDY: The Prevention of Syncope Trial (POST) is a multicentre, randomized,
      placebo-controlled, study of metoprolol in the prevention of vasovagal syncope.
      The primary hypothesis is that beta-blockers will increase the time to the first
      recurrence of syncope when compared with placebo. Patients will be randomized 1:1
      to receive metoprolol or placebo, and followed for 1 year. The primary endpoint
      is the time to first syncope recurrence, and secondary endpoints include syncope
      frequency, presyncope, and quality of life. INCLUSION AND EXCLUSION CRITERIA:
      Patients are eligible if they have a positive tilt test and 3 syncopal spells
      preceding the tilt test. They are excluded if they have seizures or other causes
      of syncope; important heart disease; a contraindication to or need for beta
      blockers; a permanent pacemaker; a major noncardiovascular disease; or previous
      use of beta blockers at a dose greater than the equivalent of metoprolol 25mg
      twice daily for the purpose of suppressing vasovagal syncope. POWER CALCULATIONS:
      We assume a 40% risk of syncope in the control arm, an absolute reduction of 20%
      by metoprolol, and a dropout of 20%. Entry of 220 patients will result in an 80%
      chance of reaching a positive conclusion about beta-blocker therapy with 2p=0.05.

PMID- 12504645
TI  - A new algorithm for rhythm discrimination in cardioverter defibrillators based on
      the initial voltage changes of the ventricular electrogram.
AB  - AIMS: Ventricular activation onset is faster in supraventricular beats than in
      ventricular rhythms. The aim of this study was to evaluate a criterion to
      differentiate supraventricular (SVT) from ventricular tachycardia (VT) based on
      the analysis of the initial voltage changes in ICD-stored morphology
      electrograms. METHODS: Far field ICD-stored EGMs were obtained from 68 VT and 38
      SVT episodes in 16 patients. The first EGM peak was detected, three consecutive
      time epochs were defined within the preceding 80 ms window and the voltage
      changes with respect to a sinus template were analysed during each time period
      and combined into a single parameter for rhythm discrimination. RESULTS: The
      algorithm was tested in an independent validation group of 442 VT and 97 SVT
      spontaneous episodes obtained from 22 patients with a dual chamber ICD. The area
      under the receiver-operator characteristics (ROC) curve indicated that the
      arrhythmia separability with this method was 0.95 (tolerance interval: 0.85-0.99)
      and 0.98 (0.87-0.99) for the control and validation groups respectively. A
      specificity of 0.91 was obtained at 95% sensitivity in the validation group.
      CONCLUSION: The analysis of voltage changes during the initial ventricular
      activation process is feasible using the far field stored electrograms of an ICD
      system and yields a high sensitivity and specificity for arrhythmia
      discrimination.

PMID- 12504646
TI  - Automatic capture verification in ICD lead systems using intracardiac ventricular
      evoked response and reduced coupling capacitance.
AB  - AIM: Intracardiac ventricular evoked-response (ER) signals detected by implanted
      cardioverter defibrillator (ICD) lead systems were investigated for automatic
      capture verification (AC). METHOD: ER signals were evaluated with an external
      pacing system equipped with a reduced coupling capacitance (CC=2.2 microF) in the
      pacing output circuit during ventricular step-down threshold testing at 0.4 ms
      pulse duration. Real-time pacing markers, surface ECG and intracardiac
      electrograms pre- and post-filtering were digitally recorded. RESULTS: Twenty
      consecutive patients, age 61+/-12 years, with leads from two different
      manufacturers were tested - 10 were implanted with acute leads (AL) and 10 with
      chronic leads (CL). The analysis was based on the ER amplitude during capture and
      on the ER-to-afterpotential ratio (SAR), with SAR>2 as the criterion for
      successful capture detection. ER amplitudes (median and range) were 8.1 mV (2.1
      19.5 mV) for AL and 8.3 mV (3.7-14.2 mV) for CL. SAR values (median and range)
      were 48.0 (2.5-682.6) for AL and 13.2 (6.3-35.9) for CL, indicating that AC could
      successfully be applied in all patients. CONCLUSIONS: Reducing the pacing CC
      allows adequate ER detection for automatic capture verification on non-selected
      ICD lead systems. The effect of high-voltage shock treatment on ER signal
      detection requires further investigation.

PMID- 12504647
TI  - The simultaneous use of a biventricular implantable cardioverter defibrillator
      (ICD) and transcutaneous electrical nerve stimulation (TENS) unit: implications
      for device interaction.
AB  - Undesirable sensing of external sources of electromagnetic interference by ICDs
      is well known. A transcutaneous electrical nerve stimulation (TENS) device has
      been reported to interfere with an ICD resulting in an inappropriate shock and
      patients with implanted defibrillators or pacemakers have been cautioned about
      the use of such units to treat chronic pain. We describe a patient regularly
      using TENS therapy for pain who subsequently received a biventricular ICD for
      malignant ventricular arrhythmias and medically refractory cardiac failure. He
      underwent testing for device interaction immediately post-implant. This did not
      show inappropriate sensing by either ICD or pacemaker component of his heart
      failure device. However, six months later, the patient complained of dizziness
      and bradycardia with application of TENS. Further testing did reveal interference
      with pacemaker function. Thus, even if initial testing is negative and
      reassuring, patients with a biventricular ICD still require careful follow-up for
      potential interaction and should be cautioned against the use of TENS, especially
      if they are pacemaker-dependent.

PMID- 12504648
TI  - Mode switching failure during atrial flutter: the '2:1 lock-in' phenomenon.
AB  - AIMS: To evaluate incidence and mechanism of a special form of automatic mode
      switching (MS) failure in patients with atrial flutter. METHODS AND RESULTS:
      Retrospectively the charts of 134 patients implanted with dual chamber pacemakers
      with MS algorithms were reviewed. Seven patients (5.2%) were identified that
      presented with sustained rapid ventricular pacing resulting from atrial flutter
      with failure of automatic MS. Since this form of MS failure implies 2:1 tracking
      of atrial flutter, it was coined '2:1 lock-in'. A theoretical timing model was
      developed to clarify the mechanism of this special form of MS failure.
      Prerequisites for the '2:1 lock-in' phenomenon are: (1). the sum of the AV delay
      and the post ventricular blanking (PVAB) must be longer than the cycle length of
      the atrial flutter, (2). the tachycardia detection rate must be higher than half
      the atrial flutter rate and (3). the maximum tracking rate (MTR) must be higher
      than half the atrial flutter rate. Recommendations for programming in order to
      avoid this specific form of MS failure are made accordingly and parallel
      algorithms for flutter detection are discussed. CONCLUSION: '2:1 lock-in' is a
      typical form of MS failure in patients with atrial flutter and the mechanism is
      closely linked to the typical atrial sensing windows.

PMID- 12504649
TI  - Diagnostic value of onset-recordings and marker annotations in dual chamber
      pacemaker stored electrograms.
AB  - AIMS: Stored electrograms (EGM) have recently been introduced into pacemaker
      therapy. New generation devices offer the possibility to store the onset of the
      EGM (several seconds preceding storage trigger) and marker annotations. The aim
      of the study was to evaluate whether the diagnostic capabilities of EGMs are
      improved by these new features. METHODS: We studied 65 patients (age 68+/-12
      years, 41 male) implanted with a DDDR-system (PulsarMax II 1280; Guidant). During
      a 1-month period 319 EGMs have been recorded. EGM triggers were: Ventricular
      Tachycardia (VT), Non-Sustained VT (NSVT), Atrial Tachycardia Response (ATR),
      Pacemaker Mediated Tachycardia (PMT) and Sudden Bradycardia Response (SBR).
      First, each EGM was analysed with onset and markers blinded. EGMs were classified
      with respect to their trigger as confirmed, not-confirmed or false-positive.
      Analysis was then repeated with markers visible but without onset, and thereafter
      vice versa. Finally, EGMs were analysed with both features. It was noted whether
      the presence of marker annotations and/or onset-recording changed the initial
      classification of the stored EGMs. RESULTS: 169 EGMs were triggered by SBR, which
      can only be confirmed with onset recording. False positive EGMs (atrial
      undersensing) occurred in 12%. The remaining 150 EGMs were triggered by ATR
      (80%), NSVT (11%), VT (6%) and by PMT (3%). Without onset/markers 37 of these 150
      EGMs (25%) could not be confirmed. With markers and onset 33/37 (89%) of these
      EGMs could now be classified as confirmed or false positive. These EGMs became
      diagnostic with onset alone in 24%, with markers alone in 24%, and with the
      combination of both in 41%. In 4 EGMs no definite diagnosis could be established.
      CONCLUSION: Stored electrograms provide direct insights into device function,
      thereby providing a validation of diagnostic data. The expanded recording of
      onset and markers results in markedly improved diagnostic capabilities - compared
      with conventional EGMs. These new features were necessary to interpret correctly
      61% of all stored electrograms, without which a diagnosis would not have been
      possible. Both onset-recording and marker annotation are necessary for optimal
      analysis.

PMID- 12504650
TI  - Effect of biventricular pacing on metabolism and perfusion in patients affected
      by dilated cardiomyopathy and left bundle branch block: evaluation by positron
      emission tomography.
AB  - AIMS: Evaluate the possible changes in myocardial metabolism and perfusion
      induced by biventricular pacing (BIVP) in patients affected by dilated
      cardiomyopathy (DC) and left bundle branch block (LBBB). METHODS AND RESULTS:
      Eight male patients (aged 60-79 years, mean 69) affected by DC (NYHA functional
      class III and ejection fraction <40%) were submitted to cardiac PET in basal
      condition and 3 weeks after the implantation of a biventricular device.
      Metabolism was evaluated using F18-fluorodeoxyglucose (FDG), by the glucose load
      insulin technique, and perfusion by N13-ammonia (NH3), injected at rest. Visual
      and a semi quantitative analyses were performed, calculating by ROIs the septum
      to lateral uptake ratio (SLR). The myocardial blood flow (MBF) was also
      calculated in ml/min/g using a dynamic acquisition and a modified Patlak method.
      In all 8 patients a selective defect in FDG uptake in the septum was present in
      basal condition (mean SLR 0.59+/-0.17) with a 'reverse mismatch' effect with
      respect to NH3 (mean SLR 1.07+/-0.18). During BIVP the distribution of FDG in the
      septal area significatively improved (mean SLR 0.86+/-0.15 P=0.011 with respect
      to basal); on the contrary, no significant changes were found in NH3 uptake (mean
      SLR 1.02+/-0.23, P=ns). On quantitative analysis the mean MBF in the septum was
      1.05+/-0.37 in basal condition and did not significantly change during BIVP
      (0.95+/-0.34, P=0.06). CONCLUSIONS: Our results suggest that, in patients
      affected by DC and LBBB, BIVP improves the septal glucose metabolism without
      significant changes in myocardial perfusion.

PMID- 12504652
TI  - Calcium channel blockers, verapamil and cancer risk.

PMID- 12504653
TI  - Changing concepts in multiple myeloma: from conventional chemotherapy to high
      dose treatment.
AB  - The treatment of Multiple Myeloma (MM), a malignant plasma cell disorder has
      changed considerably over the past decade. It has been convincingly shown that
      intensive treatment supported by autologous stem cell reinfusion is superior to
      conventional chemotherapy with alkylating agents or vincristine, doxorubicin and
      dexamethasone (VAD) alone in terms of a more rapid response and a longer disease
      free survival. However, cure is not achieved in the majority of patients. Several
      trials have therefore focussed on repeated intensive treatments in order to
      improve the survival of these patients. Other approaches are aimed at identifying
      patients on the basis of prognostic factors, who may benefit from high-dose
      therapy. This review discusses the recent developments in intensive therapy for
      multiple myeloma.

PMID- 12504654
TI  - A systematic review of molecular and biological markers in tumours of the Ewing's
      sarcoma family.
AB  - The aims of this study were to perform the first systematic review of molecular
      and biological tumour markers in tumours of the Ewing's sarcoma family (ESFT),
      and evaluate the current evidence for their clinical use. A well-defined,
      reproducible search strategy was used to identify the relevant literature from
      1966 to February 2000. Papers were independently assessed for tumour markers used
      in the screening, diagnosis, prognosis or monitoring of patients with ESFT.
      Eighty-four papers studying the use of 70 different tumour markers in ESFT's were
      identified. Low-quality, inconsistent reporting limited meta-analysis to that of
      prognostic data for 28 markers. Patients with tumours lacking S-100 protein
      expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95%
      confidence interval (CI) 0.19, 0.89) than those with expression; patients with
      high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS:
      HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised
      disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved
      DFS compared with those with other fusion transcript types (HR=0.17, 95% CI
      0.079, 0.37). The knowledge base formed should facilitate more informative future
      research. Improved statistical reporting and large, multicentre prospective
      studies are advocated.

PMID- 12504655
TI  - Response to first-line chemotherapy and long-term survival in patients with
      multiple myeloma: results of the MM87 prospective randomised protocol.
AB  - In this study we evaluated whether a good response to conventional chemotherapy,
      i.e. a significant tumour reduction, is a prerequisite for improved survival in
      multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive
      previously untreated patients with MM received chemotherapy within the
      prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were
      evaluable for both response and long-term survival and 244 (94.6%) have died. The
      median survival of all patients was 40 months (6-162 months). The median survival
      did not differ between patients who had complete response (CR) (50 months (9-162
      months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD)
      (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135
      months)) (P<0.0001) in patients whose disease progressed while they were
      receiving first induction chemotherapy. Causes of death were more frequently
      (P=0.04) related to MM in patients who had progressive disease (PD) than in
      patients who had a CR or PR or SD. The main clinical and laboratory
      characteristics were similar in the four groups. These data indicate that
      patients who maintain SD during first-line chemotherapy have a prognosis similar
      to that of patients who attain a response. Only patients whose disease progresses
      have a distinctly worse outcome.

PMID- 12504656
TI  - Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast.
AB  - The development of an invasive recurrence following treatment for ductal
      carcinoma in situ (DCIS) converts a non-fatal disease to one associated with
      mortality. To date, no pathological or molecular features have been found to
      predict for the type of recurrence. Previous studies have suggested that in DCIS
      angiogenesis may be an important factor in determining the transformation from in
      situ to invasive carcinoma. We looked at 355 cases of DCIS and found that 32 had
      subsequently developed recurrent disease. In these 32 cases and in matched
      controls, periductal vascular density was determined using morphometry and anti
      endothelial antibodies, von Willebrand factor (vWF) and CD34. Vascular density
      was related to the risk of both invasive and in situ recurrence. Normal lobules
      at least 2 mm away were used as controls. Differences in the phenotype of
      individual blood vessels was detected by performing dual staining
      immunofluorescence on selected cases. The microvessel density (MVD), as detected
      with the CD34 antibody, was higher around foci of DCIS than around normal breast
      lobules (P=0.001). Furthermore, it was significantly higher in cases of DCIS that
      recurred (P<0.0001). The findings with the vWF antibody were less clear cut and
      suggested a trend in decreasing MVD with increasingly aggressive disease. Dual
      immunofluorescence staining shows that the increase in MVD seen around DCIS is
      due to an increase in CD34+/vWF-blood vessels. An increase in CD34+/vWF-of blood
      vessels may be able to predict cases of DCIS that are at a high risk of
      developing a recurrence.

PMID- 12504657
TI  - Shortened irradiation scheme, continuous infusion of 5-fluorouracil and
      fractionation of mitomycin C in locally advanced anal carcinomas. Results of a
      phase II study of the European Organization for Research and Treatment of Cancer.
      Radiotherapy and Gastrointestinal Cooperative Groups.
AB  - The European Organization for Research and Treatment of Cancer (EORTC) 22861
      randomised trial established that combined radiochemotherapy is the standard
      treatment for locally advanced anal cancer. This EORTC phase II study (#22953)
      tests the feasibility of reducing the gap between sequences to 2 weeks, to
      deliver Mitomycin C (MMC) in each radiotherapy sequence and 5-FU continuously
      during the treatment. The first sequence consisted of 36 Gy over 4 weeks. 5-FU
      200 mg/m(2)/days 1-26, MMC 10 mg/m(2)/day 1 gap 16 days. Then a second sequence
      of 23.4 Gy over 17 days, 5-FU 200 mg/m(2)/days 1-17 and, MMC 10 mg/m(2)/day 1 was
      given. 43 patients with a World Health Organization (WHO) status of 0 (n=27) or 1
      (n=16) and with T2-T4, N0-3 tumours were included. Compliance with the planned
      treatment, doses and duration was 93%. The complete response rate was 90.7%.
      Grade 3 toxicities of 28, 12 and 2% were observed for skin, diarrhoea and
      haematological toxicities, respectively. The 3-year estimated rates for trials
      22861 and 22953 are: 68 and 88% for local control; 72 and 81% for colostomy-free
      interval, 62 and 84% for severe late toxicity-free interval, and 70 and 81% for
      survival, respectively. The 22953 scheme is feasible and the results are
      promising. This is now considered as the new standard scheme by the EORTC.

PMID- 12504658
TI  - Core biopsy versus FNAC for palpable breast cancers. Is image guidance necessary?
AB  - The aim of this study was to assess the efficacy of free-hand percutaneous core
      biopsy (FHCB) and to determine the role of fine needle aspiration cytology (FNAC)
      as diagnostic tools for palpable radiologically-suspicious breast lumps. This
      retrospective study was based on reviewing the clinical records of all patients
      diagnosed as having breast cancer between January 1999 and December 2000 and
      patients who had benign lesions, but suspicious breast imaging at triple
      assessment. Absolute sensitivity of FHCB for diagnosing cancer in palpable
      lesions was 98.7% compared with 51.3% for FNAC. The difference in the sensitivity
      of FHCB and FNAC was statistically significant (P<0.005, Wilcoxon matched pair
      test). Since 94.8% of radiologically-suspicious lumps were shown to be cancers,
      we advocate FHCB for all patients presenting with radiologically suspicious
      palpable lumps to our breast clinic. We also conclude that the sensitivity of
      FHCB for the diagnosis of malignancy in palpable radiologically-suspicious breast
      lesions is so high that image-guidance is unnecessary.

PMID- 12504659
TI  - Exercise reduces fatigue in chronic fatigued Hodgkins disease survivors--results
      from a pilot study.
AB  - The aims of this pilot study were to compare aerobic capacity in non-fatigued and
      fatigued Hodgkin's disease survivors (HDS) and to assess the feasibility of an
      exercise-programme and its effects upon fatigue, physical functioning and aerobic
      capacity in chronic fatigued HDS. 53 HDS (85%) of originally 62 survivors treated
      at the Trondheim University Hospital in the period 1987-1997 completed a
      questionnaire including the Fatigue Questionnaire (FQ). 18 subjects were
      identified with chronic fatigue. 15 non-fatigued HDS matched for gender and age
      were drawn as controls. Both groups were invited to medical examination and
      exercise tests. All 15 fifteen non-fatigued HDS showed up to the medical
      examination. 12 of the 18 patients with chronic fatigue completed the tests and
      nine agreed to enter a home-based exercise intervention. Outcome measures were
      aerobic capacity, fatigue and physical functioning. No significant difference in
      aerobic capacity was found between the chronic fatigued HDS and the controls.
      Fatigue, physical functioning and maximal aerobic capacity were significantly
      improved after the intervention. Aerobic exercise had a positive effect upon
      chronic fatigue in HDS. However, the study is a pilot study and needs
      confirmation in a larger group of subjects. The intervention was well accepted,
      and the majority of the patients adhered to the programme.

PMID- 12504660
TI  - Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset
      of patients treated with chemotherapy.
AB  - Adult patients with metastatic or locally advanced irresectable soft-tissue
      sarcoma (ASTS) are generally considered as incurable. Whether some of these
      patients achieve long-term survival after first-line treatment with chemotherapy
      is not known. Patients with ASTS still alive 5 years after initial treatment with
      a doxorubicin-containing regimen, i.e. long-term survivors, were analysed among
      the 2187 patients included in first-line chemotherapy protocols between 1976 and
      1990 in seven trials of the European Organization for Research and Treatment of
      Cancer Soft Tissue and Bone Sarcoma Group (EORTC STBSG) group. 1888 patients were
      followed for at least 5 years. The initial clinical characteristics and the
      outcome of the long-term survivors were investigated. 66 of the 1888 patients
      were alive at 5 years and the projected 5-year survival was 8% in this series.
      Age or histological subtypes were similar in the long-term survivors compared
      with the other patients. The percentages of females (69%), of grade 1 tumours
      (35%), of patients with an initial performance status (PS) of 0 (63%) were
      significantly higher in the long-term survivors while liver metastasis (6% versus
      21%) were significantly less frequent. Long-term survivors were observed in all
      subgroups of patients. 31, 31, 31 and 6% of the long-term survivors were in
      complete response (CR), partial response (PR), stable disease (SD), and
      progressive disease (PD), respectively, after the first-line regimen. A CR to a
      doxorubicin-containing regimen was the major parameter correlated to 5-year
      survival. In multivariate analysis using a logistic model, independent parameters
      correlated to 5-year survival were PS, female gender, grade I tumours, and the
      achievement of a CR after first-line treatment, which was retained as the most
      powerful predictor for 5-year survival. 10 of the 66 patients died after 5 years
      in this series, including 8 patients in PD or SD after first-line treatment
      versus 2 patients in PR or CR (P=0.01). 8% of patients with ASTS are alive 5
      years after first-line chemotherapy with a doxorubicin-containing regimen. Long
      term survivors are observed in all prognostic subgroups of patients, in
      particular those achieving a CR to first-line chemotherapy.

PMID- 12504661
TI  - Immunisation of metastatic cancer patients with MAGE-3 protein combined with
      adjuvant SBAS-2: a clinical report.
AB  - Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of
      them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3
      protein combined with a fixed dose of the immunological adjuvant SBAS-2, which
      contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.)
      injections at 3-week intervals. Patients whose tumour stabilised or regressed
      after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The
      vaccine was generally well tolerated. Among the 33 melanoma patients who were
      evaluable for tumour response, we observed 2 partial responses, 2 mixed responses
      and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29
      months. In addition, a partial response lasting 10 months was observed in 1 of
      the 3 metastatic bladder cancer patients included. None of the tumour responses
      described above involved visceral metastases. Immunological responses to the
      vaccine will be reported separately.

PMID- 12504662
TI  - Phase II study of carboplatin in patients with advanced or recurrent endometrial
      carcinoma. A trial of the EORTC Gynaecological Cancer Group.
AB  - The aim of this study was to investigate the efficacy and toxicity of carboplatin
      given as monotherapy in endometrial adenocarcinoma. Cisplatin is one of the most
      active drugs in gynaecological cancer types, but at the cost of an associated
      high toxicity. In this high-risk population of endometrial cancer patients, it is
      necessary to have chemotherapy regimens with a low toxicity. Patients eligible
      for this study were those with histologically-confirmed endometrial
      adenocarcinoma with evidence of recurrent and/or metastatic disease. Carboplatin
      was administered every 4 weeks as a first- (dose: 400 mg/m(2)) or second- (dose:
      300 mg/m(2)) line chemotherapy. Of the 64 patients who entered the trial, 60 were
      eligible, 53 patients were evaluable for toxicity and 47 for efficacy. A total of
      169 cycles of carboplatin was given with a median of 2 cycles per patient (range
      1-11 cycles) to a median cumulative dose of 798 mg/m(2) (range 290-3879 mg/m(2)).
      No grade 4 toxicity or toxic deaths occurred. White Blood Cell (WBC) toxicity
      grade 3 was noted five times, mainly in the radiotherapy pre-treated patients.
      Grade 3 non-haematological toxicity consisted mainly of nausea and vomiting
      (21%). There was a total of eight responses (3 Complete Responses (CR) and 5
      Partial Responses (PR) with an overall response rate (ORR) of 13% (95% Confidence
      Interval (CI) 6-25). No responses occurred in patients treated with prior
      chemotherapy. In evaluable patients, the ORR in all patients (n=47) and in those
      receiving first-line chemotherapy (n=33) were, 17% (95% CI 8-31) and 24% (95% CI
      11-42), respectively. After a median follow-up of 379 days, the median duration
      of response was 488 days (range 141-5303 days) with two very long responses in
      patients with a CR. Carboplatin has a low toxicity and is active in chemotherapy
      naive advanced endometrial carcinoma patients. These results lead us to propose
      its use in association in first-line chemotherapy in recurrent or advanced
      endometrial carcinoma patients. The choice of the initial dose can be determined
      according to whether the patients have received prior radiotherapy treatment.

PMID- 12504663
TI  - Heparanase gene expression and its correlation with spontaneous apoptosis in
      hepatocytes of cirrhotic liver and carcinoma.
AB  - Heparanase (hep) degrades heparan sulphate proteoglycans (HSPGs), which are the
      main components of the extracellular matrix. This process has been considered as
      the first step of tumour invasion or metastasis. However, HSPGs play an important
      role in signal transduction. Thus, the degradation of HSPGs by hep may suppress
      tumour cell growth. In the present study, we investigated the clinicopathological
      importance of enhanced hep mRNA expression in 48 hepatocellular carcinomas (HCCs)
      and in 48 non-cancerous liver samples obtained from the same patients by
      quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR).
      Spontaneous apoptosis in the hepatocytes was evaluated by immunohistochemistry.
      The relative hep mRNA expression levels were described as hep/glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) ratios. The hep mRNA levels of HCCs were
      significantly lower than those of non-cancerous livers (P<0.001). Hep mRNA levels
      decreased with increasing liver fibrosis. A significant positive correlation
      between hep gene expression and spontaneous apoptosis was detected. Hep
      expression in the tumours did not correlate with tumour differentiation or with
      tumour stage. However, low hep gene expression was associated with a poor disease
      free survival of the patients. Thus, hep gene expression may play an important
      role in programmed cell death and this gene expression may be lost during the
      malignant transformation of hepatocytes.

PMID- 12504664
TI  - Patterns of childhood cancer by ethnic group in Bradford, UK 1974-1997.
AB  - The highly urbanised northern English city of Bradford contains a diverse
      population from different ethnic backgrounds, including a high proportion of
      south Asians. We aimed to identify the effect of ethnic group on the incidence
      and temporal trends of childhood cancer in Bradford. Children (0-14 years) from
      the district of Bradford, who were diagnosed with a malignancy between 1974 and
      1997, were selected from a population-based register. Each child was classified
      as south Asian (Indian, Pakistani and Bangladeshi), or not, based on their full
      name using 2 computer algorithms and individual inspection. Mid-year population
      estimates were used to calculate incidence rates and differences were assessed
      using Poisson regression. The study included 318 children, of whom 81 (25%) were
      south Asian. The incidence of all cancers in south Asian children (14.9 per
      100,000 person years, 95% CI 11.6-18.2) was higher than non-south Asian children
      (12.0, 10.5-13.5) although not significantly so (P=0.14). Comparisons by
      diagnostic subgroup showed no major differences apart from significantly higher
      rates of acute myeloid leukaemia (AML) in south Asian children (1.9 versus 0.7,
      P=0.02). The age-specific incidence peaks of all childhood cancers and leukaemias
      were present in south Asian children aged 5-9 years compared with 0-4 years olds
      in the non-south Asian population. Non-significant increases of 1.4 and 1.5% in
      the average annual incidence of all cancers were seen for south Asians and non
      south Asians respectively, with a significant rise for non-south Asians with
      leukaemia of 3.0% (P=0.04). Our timely study shows patterns of occurrence of
      childhood cancer that differ with respect to ethnic group. Differences are
      particularly apparent in the excess of AML and incidence peak in 5-9 year olds in
      south Asian children.

PMID- 12504665
TI  - Verapamil is associated with an increased risk of cancer in the elderly: the
      Rotterdam study.
AB  - The association between the use of calcium channel blockers (CCB) and cancer has
      received ample attention, but is still controversial. In this study, we have
      tested the hypothesis that the observed association between CCB and cancer in
      earlier studies could be explained by residual confounding or by
      misclassification of exposure because of the use of cross-sectional data on drug
      use. Data from the Rotterdam Study, a prospective population-based cohort study
      in the municipal area Ommoord, were used. The study population consisted of a
      cohort of 3204 participants aged 71 years or older who were followed from a
      baseline interview in the period 1991-1993 for the occurrence of incident cancer.
      Data on drug use were gathered at baseline and through the seven community
      pharmacies which served the Ommoord region during the study period between 1
      January 1991 and 1 January 1999. Incident cancer events were gathered from a
      nationwide registry of hospitalisation data and from a specialised cancer centre
      in the Rotterdam region. We performed three analyses. First, we followed the
      method, and adjusted for the same risk factors, as in the earlier studies. In the
      second analysis, we included all risk factors that were univariately associated
      with cancer in the Rotterdam Study. In the third analysis, we included exposure
      to CCBs as time-varying co-variates, while adjusting for potential confounders.
      The relative risk (RR) of cancer associated with CCB was 1.4 (95% Confidence
      Interval (CI): 0.9-2.0) in the first analysis and lowered to 1.2 (95% CI: 0.8
      1.8) upon adjustment for the different co-variates in the second. In both
      analyses, however, verapamil was significantly associated with cancer with RRs of
      2.1 (95% CI: 1.1-4.0) and 2.0 (1.01-3.9), respectively, whereas no associations
      were found with the other CCB in this study, i.e. diltiazem and nifedipine. A
      significantly increased risk of cancer was found for intermediate daily doses of
      verapamil and diltiazem. Intake of other antihypertensives such as beta-blocking
      agents, diuretics and ACE-inhibitors was not associated with cancer. In the third
      analysis with exposure to CCB as time-varying co-variates, the risk increase was
      non-significant for use of 2 years or less, 1.0 (95% CI: 0.7-1.5), and for use
      for a cumulative period of more than 2 years, 1.3 (95% CI: 0.8-2.0). However, in
      all models the hazard ratio was statistically significantly increased for
      verapamil, but not for diltiazem and nifedipine. On the basis of these analyses,
      we found no increase in cancer in users of diltiazem and nifedipine, nor in users
      of other antihypertensives. In line with earlier studies, however, we found an
      increased risk of cancer in users of verapamil. At variance with the conclusions
      from several other studies, we think that it is too early to conclude that CCB
      are not associated with cancer.

PMID- 12504666
TI  - Geography of clinical cancer research publications from 1995 to 1999.
AB  - In this paper, we study the geography of publications in clinical cancer research
      from 1995 to 1999. A Medline search was performed to retrieve papers in clinical
      oncology reporting phase I, II and III studies published between 1995 and 1999.
      Only studies reporting antiblastic chemotherapy have been considered, either
      alone or in combination with other treatments. For each country, the total number
      of papers, the total Impact Factor (IF), and the mean IF were determined. Similar
      calculations were performed to compare the European Union versus North America.
      3142 papers were identified. The United States ranks first by number of papers
      (37.7% share), followed by Italy (9.8%), the United Kingdom (8.5%) and Japan
      (6.9%). Investigators at European institutions published a higher number of
      papers compared with their North American colleagues (1362 versus 1288). Still
      the mean IF of North American papers is higher than the papers with a European
      address (3.54 versus 3.14). The majority of phase I studies were performed in
      North America, while most of phase III studies were performed in Europe. These
      results provide information on the geography of clinical cancer research
      worldwide, which may reflect the human and economic resources involved in this
      field.

PMID- 12504667
TI  - Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines.
AB  - Oxaliplatin (L-OHP) is a new platinum analogue that has shown antitumour activity
      against colon cancer both in vitro and in vivo and is now used in the
      chemotherapeutic treatment of metastatic colon and rectal cancer. L-OHP like
      cisplatin (CDDP), is detoxified by glutathione (GSH)-related enzymes and forms
      platinum (Pt)-DNA adducts lesions that are repaired by the nucleotide excision
      repair system (NER). We investigated the cytotoxicity and the pharmacology of L
      OHP and CDDP on a panel of six colon cell lines in vitro. We showed that GSH and
      glutathione S-transferase (GST) activity were not correlated to oxaliplatin
      cytotoxicity. Pt-DNA adducts formation and repair were correlated with CDDP, but
      not with L-OHP cytotoxicity. The determination of ERCC1 and XPA expression, two
      enzymes of the NER pathway, by reverse transcriptase-polymerase chain reaction
      (RT-PCR), demonstrated that ERCC1 expression was predictive of L-OHP sensitivity
      (r(2)=0.67, P=0.02) and XPA level after oxaliplatin exposure was also correlated
      to L-OHP IC(50) (r(2)=0.5; P=0.04). The knowledge of such correlations could help
      predict the sensitivity of patients with colon cancer to L-OHP.

PMID- 12504668
TI  - Retroviral transfer of MRP1 and gamma-glutamyl cysteine synthetase modulates cell
      sensitivity to L-buthionine-S,R-sulphoximine (BSO): new rationale for the use of
      BSO in cancer therapy.
AB  - MRP1 (multidrug resistance protein 1) co-exports glutathione (GSH) and drug(s)
      and exports GSH, glucuronide, and sulphate-conjugated drugs. Human Fly-eco
      fibrosarcoma cells producing the MRP1-expressing retrovirus SF91MRP (Fly-eco
      MRP1), as well as 3T3 cells transduced with SF91MRP (3T3/MRP1), presented a
      decrease in intracellular GSH levels, as measured by two different methods. The
      enhanced export of GSH caused by the overexpression of MRP1 was partially
      counterbalanced by an increased rate of GSH synthesis. Fly-eco MRP1 and 3T3/MRP1
      were hypersensitive to the GSH-depleting and cytotoxic activities of L-buthionine
      S,R-sulphoximine (BSO), compared with their parental counterparts. In addition,
      the potentiation by BSO of the cytotoxic activity of chlorambucil and doxorubicin
      in Fly-eco MRP1 cells was greater than in parental Fly-eco cells. Although the
      turnover time of GSH, i.e. the theoretical time in which the entire GSH pool is
      resynthesised, was approximately 50% faster in Fly-eco MRP1 cells than in
      parental cells, this was not sufficient to fully restore the intracellular GSH
      level. In addition, mrp1 (-/-) mice were resistant to the GSH-depleting activity
      of intraperitoneally (i.p.) injected BSO, compared with mrp1 (+/+) mice. Co
      transfer of the cDNAs for MRP1 and the heavy subunit of gamma-glutamyl cysteine
      synthetase (GCS) resulted in increased intracellular GSH levels and in high-level
      resistance to the GSH-depleting and cytotoxic activities of BSO. These data, and
      in particular the elevated single-agent cytotoxicity of BSO, provide a new
      rationale for the use of BSO in the treatment of MRP1-overexpressing tumours.

PMID- 12504672
TI  - Veni, vidi, vici - atomic resolution unravelling the mysteries of protein
      function.
AB  - Atomic resolution macromolecular crystallography has become a powerful and
      versatile tool in structural biology; the number of atomic resolution structures
      is steadily increasing. Novel techniques are being developed and the use of
      complementary methods that span the field from sample preparation to validation
      and analysis of the resulting models has emerged. These allow the fuller
      exploitation of the information stored in crystal structures and reveal a depth
      of structural detail that was unattainable in the recent past.

PMID- 12504673
TI  - Novel proteases: common themes and surprising features.
AB  - Proteases perform a wide variety of functions, inside and outside cells,
      regulating many biological processes. Recent years have witnessed a number of
      significant advances in the structural biology of proteases, including aspects of
      intracellular protein and peptide degradation by self-compartmentalizing
      proteases, activation of proteases in proteolytic cascades of regulatory
      pathways, and mechanisms of microbial proteases in pathogenicity.

PMID- 12504674
TI  - Structural biology of enzymes involved in NAD and molybdenum cofactor
      biosynthesis.
AB  - The structural analysis of all enzymes in a metabolic pathway is a prerequisite
      to answering fascinating questions, such as those relating to the evolutionary
      relationships between enzymes within the same and related pathways. Furthermore,
      the observed impressive diversity of catalytic functions displayed by these
      enzymes can lead to the synthesis of highly complex or unstable molecules,
      frequently involving unusual chemical reactions. Moreover, a detailed description
      of the active site of each enzyme in a pathway is of immense importance for the
      rational design of new drugs. The recent progress made in the structural biology
      of enzymes involved in NAD and molybdenum cofactor biosynthesis presents a
      significant step toward these goals.

PMID- 12504675
TI  - Burning fat: the structural basis of fatty acid beta-oxidation.
AB  - Recent advances in the structural biology of the enzymes involved in fatty acid
      oxidation have revealed their catalytic mechanisms and modes of substrate
      binding. Although these enzymes all use coenzyme A (CoA) thioesters as
      substrates, they share no common polypeptide folding topology or CoA-binding
      motif. Each family adopts an entirely unique protein fold. Their mode of binding
      the CoA thioester is similar in that the fatty-acyl moiety is buried inside the
      protein and the nucleotide portion is mainly exposed to solvent; however, the
      conformations of the enzyme-bound CoA ligands vary considerably. Furthermore, a
      comparison of these structures suggests a structural basis for the broad
      substrate chain length specificity that is a unique feature of these enzymes.

PMID- 12504676
TI  - Protein complexes gain momentum.
AB  - The greatest challenge to structural biologists in the post-genomic era is to
      decipher both stable and transient interactions of protein complexes. In response
      to this challenge, significant advances in mass spectrometry have been made in
      the past two years. With the inception of novel approaches targeted at defining
      interaction partners, stoichiometry and topology, as well as monitoring real-time
      reactions, mass spectrometry is well placed to contribute to the understanding of
      dynamic macromolecular complexes.

PMID- 12504677
TI  - Protein tyrosine kinases: autoregulation and small-molecule inhibition.
AB  - Receptor and non-receptor protein tyrosine kinases (PTKs) are essential enzymes
      in cellular signaling processes that regulate cell growth, differentiation,
      migration and metabolism. The kinase activity of PTKs is tightly controlled
      through steric, autoregulatory mechanisms, as well as by the action of protein
      tyrosine phosphatases. Recent structural studies have revealed several modes of
      autoregulation governing the catalytic state of these enzymes. Aberrant catalytic
      activity of many PTKs, via mutation or overexpression, plays an important role in
      numerous pathological conditions, including cancer. Structural studies of the Abl
      tyrosine kinase domain in complex with the small-molecule inhibitor STI571
      provide a molecular basis for understanding the specificity determinants of this
      highly successful drug used in the treatment of chronic myeloid leukemia.

PMID- 12504679
TI  - AAA proteins.
AB  - AAA proteins have entered the molecular realm after being known primarily for
      their wide range of different functions. Structural studies have highlighted the
      organization of their constituent ATPase domains and indicate that hexamerization
      in combination with unfoldase activity is a common underlying feature of this
      ubiquitous protein family.

PMID- 12504680
TI  - Structure and mechanism of ABC transporters.
AB  - ATP-binding cassette (ABC) transporters are central to many physiological
      processes, including the uptake of nutrients, the non-classical secretion of
      signaling molecules and toxins, multidrug resistance and the development of human
      disease. As one might expect from this spectrum of translocation events, these
      ubiquitous, ATP-dependent pumps or channels are capable of transporting an
      enormous variety of substrates, ranging from small ions to large proteins.
      Recently determined structures of full-length ABC transporters and isolated ABC
      domains have increased our understanding of the functional mechanism of these
      proteins.

PMID- 12504681
TI  - Regulation of protein kinases in insulin, growth factor and Wnt signalling.
AB  - Protein kinase cascades provide the regulatory mechanisms for many of the
      essential processes in eukaryotic cells. Recent structural and biochemical work
      has revealed the basis of phosphorylation regulation of three consecutive protein
      kinases - phosphoinositide-dependent kinase 1 (PDK1), protein kinase B (PKB)/Akt
      and glycogen synthase kinase 3beta (GSK3beta) - which transduce signals generated
      by insulin and/or growth factors binding to cell surface receptors. PDK1 and PKB
      are both AGC family kinases. Whereas PKB is positively regulated via its
      phosphorylated C-terminal hydrophobic motif, the activity and specificity of PDK1
      are determined by equivalent hydrophobic motifs of substrate AGC kinases. In a
      contrasting mechanism, GSK3beta is negatively regulated by competitive
      autoinhibition by its phosphorylated N terminus. GSK3beta also functions in the
      developmental Wnt signalling pathway, but without cross-talk with the PDK1
      PKB/Akt pathway. Structural studies of GSK3beta complexes are contributing to our
      understanding of the phosphorylation-independent mechanism that insulates the Wnt
      and insulin/growth factor pathways.

PMID- 12504682
TI  - Structure and function of the Arp2/3 complex.
AB  - The Arp2/3 complex, a 220 kDa macromolecular assembly comprising two actin
      related proteins and five other subunits, plays a key role in cellular motility
      by initiating the polymerization of new actin filaments. Crystal and cryo
      electron microscopic structures of the Arp2/3 complex and branch junctions have
      clarified extensive biochemical data on the mechanism of this process.

PMID- 12504683
TI  - Catalysis in the nitrilase superfamily.
AB  - Recently, we defined the nitrilase superfamily as consisting of 12 families of
      amidases, N-acyltransferases and presumptive amidases, in addition to the family
      of plant and bacterial nitrilases for which the superfamily was named. A novel
      Glu-Lys-Cys catalytic triad, found at the crystallographically defined Nit active
      site of worm NitFhit, was postulated to constitute the catalytic residues for all
      members of the superfamily. Recent experimental results confirm the essentiality
      of the catalytic triad residues and specify the biochemical functions of
      additional branches and sub-branches of the nitrilase superfamily.

PMID- 12504684
TI  - SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold.
AB  - The S-adenosylmethionine-dependent methyltransferase enzymes share little
      sequence identity, but incorporate a highly conserved structural fold.
      Surprisingly, residues that bind the common cofactor are poorly conserved,
      although the binding site is localised to the same region of the fold. The
      substrate-binding region of the fold varies enormously. Over the past two years,
      there has been a significant increase in the number of structures that are known
      to incorporate this fold, including several uncharacterized proteins and two
      proteins that lack methyltransferase activity.

PMID- 12504685
TI  - OB-fold domains: a snapshot of the evolution of sequence, structure and function.
AB  - The OB-fold is found in all three kingdoms and is well represented in both
      sequence and structural databases. The OB-fold is a five-stranded closed beta
      barrel and the majority of OB-fold proteins use the same face for ligand binding
      or as an active site. Different OB-fold proteins use this 'fold-related binding
      face' to, variously, bind oligosaccharides, oligonucleotides, proteins, metal
      ions and catalytic substrates. Recently, a number of new structures with OB-folds
      have been reported that augment the variation seen for this set of proteins
      whilst conserving the characteristic fold and binding face. The conservation of
      fold and a functional binding face amongst many structures provides a model for
      investigating the evolutionary trajectory of sequence, structure and function.

PMID- 12504686
TI  - Predicted and experimental structures of integrins and beta-propellers.
AB  - Integrins and other cell surface receptors have been fertile grounds for
      structure prediction experiments. Recently determined structures show remarkable
      successes, especially with beta-propeller domain predictions, and also reveal how
      ligand binding by integrins is conformationally regulated.

PMID- 12504687
TI  - Endocytosis and vesicle trafficking.
AB  - Several common themes have emerged from recent structural and functional studies
      of proteins involved in the formation of coated vesicles. For example, inositol
      polyphosphate lipid headgroups are bound specifically by a variety of different
      domains in ways appropriate to domain function. Another theme is the recognition
      of short sequence motifs in structureless regions of other coat components,
      allowing dynamic multicomponent networks to be established.

PMID- 12504688
TI  - Structural basis of ubiquitylation.
AB  - The attachment of the small protein ubiquitin to other proteins, a process known
      as ubiquitylation, is a widespread form of post-translational modification that
      regulates numerous cellular functions in eukaryotes. Ubiquitylation is performed
      by complexes of E2 and E3 enzymes that are assembled and select substrates via a
      series of protein-protein interactions. Recent structure determinations of the
      ubiquitylation machinery have revealed some of the various protein-protein
      interfaces involved.

PMID- 12504689
TI  - Photodynamic therapy using verteporfin for choroidal neovascularization in
      angioid streaks.
AB  - PURPOSE: To evaluate the efficacy of photodynamic therapy with verteporfin in the
      management of choroidal neovascularization (CNV) associated with angioid streaks.
      DESIGN: Retrospective case series. METHODS: Eleven eyes of nine patients with
      subfoveal or juxtafoveal CNV due to angioid streaks underwent visual acuity
      testing, ophthalmic examination, color photography, and fluorescein angiography
      to evaluate the results of photodynamic therapy with verteporfin. Retreatment of
      persistent CNV was based on criteria from the Treatment of Age-Related Macular
      Degeneration with Photodynamic Therapy Investigation (TAP) except in one case.
      Follow-up ranged from 5 to 28 months (mean, 17 months). RESULTS: Nine of 11 eyes
      had subfoveal lesions while two eyes had juxtafoveal lesions on initial
      examination. Conversion from a choroidal neovascular membrane (CNVM) to a fibrous
      disciform lesion following photodynamic therapy was observed in nine eyes.
      Enlargement of the CNVM was noted in seven of these eyes by fluorescein
      angiography at final follow-up. Initial best-corrected visual acuity (BCVA)
      ranged from 20/25 to counting fingers (CF) (mean, 20/400; median, 20/200). Final
      BCVA ranged from 20/20 to CF (mean, 20/600; median, 20/400). Seven eyes with
      subfoveal CNVM had an initial BCVA of at least 20/200 while only three eyes
      maintained this level or better at last follow-up. In one patient with a
      juxtafoveal CNVM in one eye, vision decreased from 20/25 to 20/400 with
      enlargement and fibrosis of the CNVM and subfoveal extension. In the fellow eye a
      juxtafoveal CNVM was initially treated and then retreated earlier than TAP
      criteria at 6 weeks. Vision improved to 20/20 and has remained stable 5 months
      after the initial treatment. CONCLUSIONS: Verteporfin for choroidal
      neovascularization-associated with angioid streaks does not appear to
      significantly alter the course of this disease with most eyes undergoing
      enlargement and disciform transformation of the neovascular process. However,
      aggressive management of these patients with biomicroscopic and fluorescein
      angiographic examination and timely photodynamic therapy with early retreatment
      when indicated may be beneficial in certain cases.

PMID- 12504690
TI  - Expression of extradomain-B-containing fibronectin in subretinal choroidal
      neovascular membranes.
AB  - PURPOSE: To investigate the presence of the fibronectin isoform containing the
      extradomain B (B-FN), a marker-protein of angiogenesis, in surgically excised
      human choroidal neovascular membranes (CNVM) to evaluate whether B-FN could be
      used as a therapeutic target for specific antibody-photosensitizer
      immunoconjugates. DESIGN: Laboratory investigation. METHODS: The setting was an
      institutional practice. The study population consisted of 15 eyes (15 patients)
      with CNVM undergoing membrane excision (four eyes with age-related macular
      degeneration, seven with pathologic myopia and four with multifocal choroiditis).
      The control group consisted of eight eye bank eyes (four subjects) without
      choroidal neovascularization. Light microscopic immunohistochemistry on cryostat
      sections of tissues was obtained. B-FN was detected by a human recombinant
      antibody, CGS-1, and compared with immunostaining for endothelial cells with
      factor VIII-related antigen. The main outcome measure was the presence of CGS-1
      positively stained cells or areas of the extracellular matrix. Staining of CGS-1
      was scored on a scale from 0 to 3. RESULTS: Fourteen of 15 neovascular membranes
      stained strongly with CGS-1 (score 2 or 3). One membrane from a patient with
      pathologic myopia was negatively stained (score 0). CGS-1 positive staining was
      detected around endothelial cells and in the extracellular matrix of CNVMs. The
      retina of eyes without choroidal neovascularization was negative with CGS-1 in
      all eight donor eyes, while the choroid contained some weakly CGS-1 positive
      cells (score 0 and 1, respectively). CONCLUSIONS: The extradomain B is abundantly
      expressed in CNVMs, but its expression is more restricted in eyes harboring no
      apparent choroidal neovascularization. In the future, B-FN might serve as a
      target for the delivery of antibody-photosensitizer immunoconjugates to newly
      developed vessels to enhance the selectivity of photodynamic therapy.

PMID- 12504691
TI  - Early postoperative retinal thickness changes and complications after vitrectomy
      for diabetic macular edema.
AB  - PURPOSE: To determine the early postoperative changes in retinal thickness and
      complications after pars plana vitrectomy for diabetic macular edema. DESIGN:
      Consecutive interventional case series. METHODS: Studied retrospectively, pars
      plana vitrectomy was performed on 65 consecutive eyes of 63 patients with
      diabetic macular edema. The follow-up interval ranged from 6 to 36 months (12.6
      +/- 7.4 months [mean +/- standard deviation (SD)]). The indications of pars plana
      vitrectomy in this study were (1) diffuse diabetic macular edema, (2)
      preoperative visual acuity less than 20/40, and (3) noneffective macular
      photocoagulation therapy. Preoperative and postoperative examinations by
      stereoscopic biomicroscopy, color fundus photography of the macula and optical
      coherence tomography (OCT) were performed on all eyes. Preoperatively, direct
      photocoagulation to microaneurysms in the macula had been performed in 48 eyes,
      and focal/grid photocoagulation had been performed in five eyes. Preoperative
      examination showed that epiretinal membranes were observed in 20 eyes, cystoid
      macular edema in 40 eyes, and 23 eyes had a complete posterior vitreous
      detachment (PVD). Epimacular membranes, removed during surgery, were examined
      histopathologically. RESULTS: The postoperative mean best-corrected visual acuity
      (logarithm of the minimum angle of resolution [logMAR] = 0.696 +/- 0.491 [mean +/
      SD]) was significantly better than the preoperative mean best-corrected visual
      acuity (0.827 +/- 0.361; P <.0001; Wilcoxon signed-rank test). The final visual
      acuity improved by 2 or more lines in 32 of 65 eyes (45%), remained unchanged in
      32 of 65 eyes (49%), and exacerbated after the surgery in 4 of 65 eyes (6%) due
      to neovascular glaucoma (2 eyes) and residual cystoid macular edema (2 eyes). The
      postoperative foveal retinal thickness (224.9 +/- 116.9 microm) at the last visit
      was significantly thinner than the preoperative foveal retinal thickness (463.7
      +/- 177.3 microm; P <.0001; Wilcoxon signed-rank test). The foveal retinal
      thickness did not decrease linearly but fluctuated: The mean postoperative
      retinal thickness had decreased significantly 7 days after surgery, then remained
      unchanged for approximately 1 month, and thereafter gradually decreased until 4
      months. The intraoperative and postoperative complications included peripheral
      retinal tear in 3 of 65 (4.6%) eyes, postoperative rhegmatogenous retinal
      detachment in 1 of 65 (1.5%) eyes, neovascular glaucoma in 3 of 65 (5%) eyes,
      recurrent vitreous hemorrhage in 1 of 65 (1.5%) eyes, hard exudates in the center
      of the macula in 3 of 56 (4.6%) eyes, postoperative epiretinal membrane formation
      in 9 of 65 (13.8%) eyes, and a lamellar macular hole in 1 of 65 (1.5%) eyes.
      CONCLUSIONS: Vitrectomy for diabetic macular edema is an effective procedure for
      reducing the edema and improving visual acuity. Because the postoperative
      reduction in retinal thickness is not complete until 4 months, the assessment of
      vitrectomy on foveal thickness should not be made until this time. In addition,
      there are severe complications from vitrectomy for diabetic macular edema, and
      careful preoperative and postoperative examinations and surgical methods are
      required.

PMID- 12504692
TI  - Genotypic analysis of cytomegalovirus retinitis poorly responsive to intravenous
      ganciclovir but responsive to the ganciclovir implant.
AB  - PURPOSE: To determine whether cytomegalovirus (CMV) retinitis that responded
      poorly to intravenous ganciclovir therapy but responded to the ganciclovir
      implant was caused by virus with resistance mutations in the viral UL97 and UL54
      genes. DESIGN: Retrospective chart review and laboratory-based experimental
      study. METHODS: Regions of the CMV UL97 and UL54 were amplified from the vitreous
      and analyzed for resistant mutations by a combination of DNA sequencing and
      restriction digestion. Vitreous from patients with AIDS and retinal infections
      other than CMV retinitis served as negative controls. RESULTS: We amplified all
      target regions of UL97 DNA and most target regions of UL54 DNA from eight eyes
      with CMV retinitis. In one eye we found a ganciclovir resistance mutation at base
      1781 of the UL97 gene, predicting an alanine to valine mutation at codon 594. In
      a second eye we found a ganciclovir resistance mutation at base 2960 of the UL54
      gene, predicting an alanine to glycine mutation at codon 987. In two additional
      eyes, both from patients with bilateral retinitis, we found UL54 mutations that
      are likely to confer resistance to ganciclovir but have not been previously
      described. In both of these patients the UL54 genotype differed between the two
      diseased eyes. CONCLUSIONS: Failure to control CMV retinitis with intravenous
      ganciclovir does not necessarily imply infection with a virus having a known
      mutation that confers drug resistance. The ganciclovir implant can be an
      effective therapy for CMV retinitis caused by virus with certain UL97 and UL54
      resistance mutations. Cytomegalovirus UL54 genotypes can differ between eyes in
      patients with bilateral retinitis.

PMID- 12504693
TI  - Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with
      cytomegalovirus retinitis.
AB  - PURPOSE: To evaluate whether cytomegalovirus resistant to ganciclovir, detected
      in either the blood or urine, correlates with adverse ocular outcomes. DESIGN:
      Prospective cohort study. METHODS: Patients with cytomegalovirus and AIDS were
      enrolled in a study of the occurrence and clinical correlates of resistant
      cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at
      the time of diagnosis of retinitis, 1 and 3 months after the initiation of
      therapy, and every 3 months thereafter. Patients were seen monthly, at which time
      fundus photographs were obtained and forwarded to the Fundus Photograph Reading
      Center for evaluation of retinitis progression (movement of a border of a
      cytomegalovirus lesion > or = 750 microm, or the occurrence of a new lesion > or
      = 0.25 disk area in size) and the amount of retinal area affected by
      cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual
      acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 > 6.0
      micromol/l, and genotypic resistance to ganciclovir was defined as the occurrence
      of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance.
      Time-dependent analyses were performed and included viral resistance, highly
      active antiretroviral therapy, and treatment variables as predictors of clinical
      outcomes. RESULTS: One hundred ninety-seven patients received ganciclovir
      therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18
      developed genotypic resistance. The detection of cytomegalovirus resistant to
      ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of
      retinitis progression (P values all < or = .0002), depending upon the definition
      of resistance and the culture sources analyzed. Resistance was associated with a
      greater increase in retinal area involved by cytomegalovirus by 3-month interval
      (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and
      for genotypic resistance in the blood or urine (P =.012 to.021). There was a
      suggestion that resistance was associated with a greater loss of visual acuity (P
      =.009 to.096). Highly active antiretroviral therapy was associated with an
      approximate 50% reduction in the odds of retinitis progression, and the
      ganciclovir implant was associated with an approximate 60% reduction.
      CONCLUSIONS: The detection of cytomegalovirus resistant to ganciclovir in either
      the blood or urine of a patient with cytomegalovirus retinitis is associated with
      an increased risk of adverse ocular outcomes.

PMID- 12504694
TI  - Detection of glaucomatous visual field defect by nonconventional perimetry.
AB  - PURPOSE: To report the correlations among Humphrey Field Analyzer 750 (HFA), high
      pass resolution perimetry (HRP), and frequency-doubling technology (FDT)
      perimetry in glaucoma patients and ocular hypertensive patients. DESIGN: Cross
      sectional study. METHODS: Eighty-two eyes of 82 consecutive patients with primary
      open-angle glaucoma (POAG) or ocular hypertension were included in this study.
      One eye of each patient was randomly selected for data analysis. Visual fields
      were assessed by HFA, HRP, and FDT perimetry. HRP global deviation (HRP-GD), HRP
      local deviation (HRP-LD), FDT-mean deviation (FDT-MD), and FDT-pattern standard
      deviation (FDT-PSD) were considered for the analysis. Clinical agreement between
      HRP and FDT was evaluated. All data were analyzed by Pearson r coefficient when
      the distribution of the data was normal and by Spearman coefficient correlation
      when the distribution of the data was not normal. A P <.05 was considered
      statistically significant. RESULTS: Fifty-two eyes (52 patients) were classified
      as glaucoma and 30 eyes (30 patients) as ocular hypertension. In the entire
      group, a significant (P >.001) correlation was found between the HFA indices and
      those of either HRP or FDT. A significant (P <.001) correlation was found between
      HRP-GD and FDT-MD as well as between HRP-LD and FDT-PSD. In 14% of the
      glaucomatous patients and in 33% of the subjects with ocular hypertension, FDT
      and HRP showed different clinical features. CONCLUSIONS: Our data suggest that
      FDT and HRP are useful for detection of early glaucomatous visual field damage.

PMID- 12504695
TI  - Iridociliary apposition in plateau iris syndrome persists after cataract
      extraction.
AB  - PURPOSE: To evaluate the ultrasound biomicroscopic appearance of the anterior
      segment before and after cataract extraction in eyes with plateau iris syndrome
      and to determine the effect of postoperative zonular relaxation on ciliary body
      position. DESIGN: Interventional case series. METHODS: Eyes with plateau iris
      syndrome scanned before and after cataract extraction between January 1994 and
      September 2001 were enrolled. The iridociliary relationship and the anterior
      chamber depth at a distance of 3 mm from the scleral spur were assessed. RESULTS:
      We examined six eyes of six patients. Mean patient age was 74.2 +/- 6.4 years
      (standard deviation [SD]) (range, 65-81 years). Mean refractive error was + 1.0
      +/- 3.9 diopters [D] (range, -5.75-+5.50), and mean axial length was 21.85 +/-
      0.77 mm (range, 20.90-22.95 mm). All eyes had undergone laser iridotomy and argon
      laser peripheral iridoplasty before cataract extraction. Ultrasound biomicroscopy
      examination revealed a narrow angle and absence of a ciliary body sulcus in all
      eyes with focal areas of iridotrabecular apposition in three eyes. Following
      cataract extraction, the anterior chamber depth increased (P =.0006, paired t
      test), while the iridociliary contact remained unchanged. CONCLUSIONS:
      Iridociliary apposition persists after cataract extraction in plateau iris
      syndrome. Whether the cause is congenital or acquired, or both, remains to be
      determined.

PMID- 12504696
TI  - Reliability of the disk damage likelihood scale.
AB  - PURPOSE: To report the reliability of the glaucoma disk damage likelihood scale
      (DDLS) in comparison to the Armaly cup/disk ratio by determining the
      interobserver and intraobserver agreement for optic disk stereo photographs and
      the interobserver agreement for in vivo patient measurements of the optic disk.
      DESIGN: Observational case series. METHODS: Optic disk photographs: 48 stereo
      pairs of optic nerve photographs were selected from patients with a spectrum of
      glaucomatous visual field loss. Two masked observers graded the optic disk
      photographs three times according to the DDLS and Armaly cup/disk ratio.
      Interobserver and intraobserver agreements were calculated using the test-retest
      method. Patient measurements: three observers performed in vivo patient
      measurements on 34 eyes of glaucoma clinic patients and made a single
      determination of the DDLS stage and Armaly cup/disk ratio, based on the indirect
      biomicroscopic examination. Level of interobserver agreement was tabulated.
      RESULTS: Optic disk photographs: interobserver and intraobserver agreement for
      the vertical DDLS measurement was greater than for two determinations (clinical
      impression and measured) of the vertical Armaly cup/disk ratio (interobserver:
      85% vs 68% and 74%, respectively; intraobserver grader 1: 97% vs 89% and 80%,
      grader 2: 99% vs 95% and 89%, respectively). In vivo patient measurements: the
      interobserver agreement for the DDLS and Armaly cup/disk ratio was similar (70.1%
      vs 67.6%, respectively). CONCLUSIONS: For the stereo optic disk photographs, the
      inter- and intra-observer agreement for the DDLS is greater than the Armaly
      cup/disk ratio. For the in vivo patient measurements, the level of agreement for
      the DDLS and the Armaly cup/disk ratio is similar.

PMID- 12504697
TI  - Neural networks to identify glaucomatous visual field progression.
AB  - PURPOSE: To describe a method to determine progression of glaucoma based on
      visual field thresholds. DESIGN: Observational retrospective longitudinal cohort
      study. METHODS: A back propagation neural network with three hidden layers was
      developed with commercial software. Visual field data from 80 patients who
      participated in the Advanced Glaucoma Intervention Study (AGIS) were used.
      Glaucomatous visual field progression was defined as a change of 4 or more units
      in the AGIS score, confirmed by at least two sequential subsequent tests. Inputs
      to the neural network consisted of threshold measurements from 55 visual field
      locations from the baseline examination and each follow-up examination. The data
      set was randomized so the sequence of examinations would not influence the
      training or testing of the neural network. Two thirds of the randomized data were
      used for training and the remaining one third for testing. RESULTS: The mean age
      of 80 patients enrolled in AGIS at initial examination was 67.4 (+/- 7.3 standard
      deviation [SD]) years. The average follow-up period was 7.2 (+/-2.3 SD) years and
      the mean duration between examinations was 0.46 (+/- 0.39 SD) years. The neural
      network estimated the probability of progression for each baseline and follow-up
      comparison with an average sensitivity of 86% and specificity of 88%. The area
      under the receiver operating characteristic (ROC) curve was 0.92, with a
      sensitivity of 86% at the 80% specificity level and a sensitivity of 91% at the
      90% specificity level. CONCLUSIONS: From analysis of AGIS data, progression of
      glaucoma could be detected from visual field thresholds with a neural network.

PMID- 12504698
TI  - A six-month randomized clinical trial comparing the intraocular pressure-lowering
      efficacy of bimatoprost and latanoprost in patients with ocular hypertension or
      glaucoma.
AB  - PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety
      of topical bimatoprost 0.03% with latanoprost 0.005%. DESIGN: Multicenter,
      randomized, investigator-masked clinical trial. METHODS: After washout of
      glaucoma medications, ocular hypertension or glaucoma patients were randomly
      assigned to once-daily bimatoprost 0.03% (n = 133) or latanoprost 0.005% (n =
      136) for 6 months. The primary outcome measure was mean change from baseline IOP
      (8 AM, 12 PM, 4 PM). Secondary measures included mean IOP, ophthalmologic
      examination, adverse events, and the percentage of patients reaching specific
      target IOPs. RESULTS: Mean change from baseline IOP was significantly greater for
      bimatoprost patients than for latanoprost patients at all measurements on each
      study visit; 1.5 mm Hg greater at 8 AM (P <.001), 2.2 mm Hg greater at 12 PM (P
      <.001), and 1.2 mm Hg greater at 4 PM (P =.004) at month 6. At the end of the
      study, the percentage of patients achieving a > or = 20% IOP decrease was 69% to
      82% with bimatoprost and 50% to 62% with latanoprost (P < or = .003). In
      addition, the distribution of patients achieving target pressures in each range
      (< or = 13 to < or = 15 mm Hg, >15 to < or = 18 mm Hg, and > 18 mm Hg) showed
      that bimatoprost produced lower target pressures compared with latanoprost at all
      times measured (P < or = .026). Few patients were discontinued for adverse events
      (6 on bimatoprost; 5 on latanoprost). On ophthalmologic examination, conjunctival
      hyperemia (P <.001) and eyelash growth (P =.064) were more common in bimatoprost
      patients. CONCLUSIONS: Bimatoprost is more effective than latanoprost in lowering
      IOP. Both drugs were well tolerated, with few discontinuations for adverse
      events.

PMID- 12504699
TI  - Management of keratoconus with Intacs.
AB  - PURPOSE: To prospectively study the effects of the use of Intacs microthin
      prescription inserts for the management of keratoconus. DESIGN: Prospective
      nonrandomized clinical trial. METHODS: Thirty-three eyes of 26 keratoconus
      patients (17 males and 9 females) ages 21 to 51 years (mean age, 32 +/- 9.7
      years) were included in the current study. All patients had clear central corneas
      and contact lens intolerance. Patients were excluded if any of the following
      criteria applied after the preoperative examination: previous intraocular or
      corneal surgery; history of herpes keratitis; diagnosed autoimmune disease; and
      systemic connective tissue disease. Two Intacs segments of 0.45-mm thickness were
      inserted in the cornea of each eye, aiming at embracing the keratoconus area to
      try to achieve maximal flattening. Preoperative examination included uncorrected
      visual acuity (UCVA), best-corrected visual acuity (BCVA), manifest refraction,
      keratometric data, and corneal topography. RESULTS: Intacs were successfully
      implanted in all eyes. In one eye Intacs were removed after 3 months because of
      their improper (superficial) placement. The follow-up ranged from 1 to 24 months
      (mean: 11.3 months). The mean UCVA significantly improved from 0.13 +/- 0.14
      (range, counting fingers [CF]-0.5) to 0.39 +/- 0.27 (range, CF-1.0) (P <.01). Of
      33 eyes, 2 eyes lost 1 line of UCVA, and 3 eyes maintained the preoperative UCVA,
      whereas the rest (28 eyes) experienced a 1- to 10-line gain. The mean BCVA also
      improved from 0.47 +/- 0.31 (range, CF-1.0) to 0.64 +/- 0.26 (range, 0.1-1.0) (P
      <.01). Of 33 eyes, 4 eyes experienced 1- to 2-line loss of BCVA, 4 eyes
      maintained the preoperative BCVA, whereas the rest (25 eyes), experienced a 1- to
      6-line gain. Of 3 patients (3 eyes) with unsatisfactory results, 1 patient
      improved with one segment removal and in 2 patients the segments were permanently
      removed. One of these eyes underwent successful PKP. CONCLUSIONS: With mean
      follow-up of 11.3 months, intracorneal ring segments implantation improved UCVA
      and BCVA in the majority of the keratoconus patients. Even though the results are
      encouraging, concern still exists regarding the predictability as well as the
      long-term effect of such an approach for the management of keratoconus.

PMID- 12504700
TI  - Anterior segment indocyanine green angiography in pterygium surgery with
      conjunctival autograft transplantation.
AB  - PURPOSE: To assess indocyanine green angiography (ICGA) as a method for
      monitoring autograft perfusion after pterygium excision with limbal-conjunctival
      autograft transplantation (LCAT) and to compare ICGA with anterior segment
      fluorescein angiography (ASFA). DESIGN: Nonrandomized prospective interventional
      case series. METHODS: Twelve eyes of 11 patients with primary pterygium treated
      by excision and limbal-conjunctival autograft transplantation were studied in a
      clinical practice. Anterior segment fluorescein angiography and ICGA findings for
      autograft vascularization after pterygium surgery were compared in 12 eyes of the
      11 patients. Graft perfusion was monitored for 1 month with ASFA and ICGA, on
      days 1,7, and 30 post-surgery. RESULTS: With ASFA no graft perfusion was observed
      by postoperative day 30; only five grafts were isofluorescent with some
      vascularization, while the remaining seven grafts were hypofluorescent without
      any vascularization. In contrast, ICGA showed that, on postoperative day 1, all
      12 grafts were hypofluorescent with multiple hyperfluorescent foci at the graft
      margin in the late phase and that, by postoperative day 7, 10 grafts were
      hypofluorescent and appeared to be perfused, originating from the episcleral
      vascular bed. On day 30, ICGA demonstrated isofluorescent grafts in 10 eyes with
      some conjunctival and episcleral vascular patterns on the graft itself, including
      the conjunctiva adjacent to the graft. By this stage, perfusion of the graft was
      complete. CONCLUSION: Indocyanine green angiography is useful for monitoring
      graft perfusion after LCAT in pterygium surgery. Further studies are needed to
      identify the implications of graft perfusion for therapy following LCAT in
      patients with pterygium.

PMID- 12504701
TI  - Endonasal dacryocystorhinostomy with mucosal flaps.
AB  - PURPOSE: To describe a new endonasal dacryocystorhinostomy (DCR) technique and
      assess its efficacy. DESIGN: Prospective nonrandomized interventional case
      series. METHODS: A prospective series of 44 consecutive endonasal DCRs performed
      from January 1999 to December 2000 was entered into the study. The new technique
      involved creation of a large bony ostium and mucosal flaps to create an
      anastamosis between the lacrimal sac mucosa and nasal mucosa. Patients presenting
      with naso-lacrimal duct obstruction based on symptomatic, clinical, and
      radiologic grounds were included in the study. Patients who had undergone
      previous lacrimal surgery were excluded. Surgery was performed by two surgeons
      (A.T., P.J.W.) using a standardized operative technique. Patient demographics,
      presentation, examination findings, surgical and anesthetic data, postoperative
      success, complications, and follow-up were evaluated. Success was defined as
      anatomic patency as well as relief of symptoms as assessed by fluorescein flow on
      nasendoscopy, lacrimal syringing, and patient examination. Intubation of the
      lacrimal apparatus was performed in all operations and the tubes usually removed
      at 4 to 6 weeks postoperatively. After removal of the tubes follow-up was 13
      months (mean, 12.9 months; range, 9-28 months; standard deviation [SD], 6.1
      months). RESULTS: There were 36 patients (12 male/24 female) who underwent 44
      endonasal DCRs. The average age of the patients was 62.9 years old (range, 15-86
      years old; SD, 19.1 years) and the main presentation was with epiphora (93%)
      and/or mucocoele (33%). In 13 operations (30%) a septoplasty was required at the
      time of surgery, and in 10 operations (23%) further endoscopic sinus surgery was
      performed in conjunction with the DCR. Anatomic success with a patent
      nasolacrimal system was achieved in 40 of 44 operations (91%). Symptomatic and
      anatomic success was seen in 39 of 44 operations (89%). Five of the DCRs were
      classified as failures. In one DCR the patient was symptomatic despite a patent
      nasolacrimal system and well-healed ostium. In two DCRs preoperative medial
      canalicular problems were noted. In two DCRs scarring and fibrosis of ostium were
      noted. CONCLUSIONS: This new technique of endonasal DCR involves creation of a
      large ostium and construction of nasal and lacrimal sac mucosal flaps. Its
      anatomic success rate (91% or 40 of 44 DCRs) compares favorably with the success
      rate of other techniques for endonasal DCR and is also similar to the success of
      external DCR. Experience in endoscopic nasal surgery is important in endonasal
      DCR surgery, as other ancillary procedures may be required within the nose at the
      time of surgery.

PMID- 12504702
TI  - Randomized, clinical trial of multiquadrant hydrodissection in pediatric cataract
      surgery.
AB  - PURPOSE: Evaluate efficacy of multiquadrant cortical-cleaving hydrodissection in
      pediatric cataract surgery. DESIGN: Randomized multicenter clinical trial.
      METHODS: Surgery performed at Iladevi Cataract & IOL Research Center (57 eyes, 42
      patients) and Postgraduate Institute of Medical Education and Research (23 eyes,
      17 patients). Study population comprised 59 consecutive patients (80 eyes) 12
      years old and younger undergoing cataract aspiration. The intervention procedure
      involving envelope randomization was used to assign patients to multiquadrant
      cortical-cleaving hydrodissection (HY) (40 eyes), or no hydrodissection (HN) (40
      eyes). The main outcome measures were as follows: (1) lens-substance removal time
      and volume of fluid used and (2) ease of lens substance removal. Presence or
      absence of residual fibers on the posterior capsule was recorded. RESULTS: The
      mean +/- standard deviation lens substance removal time was significantly less in
      the HY group (156.1 +/- 86.8 seconds) than in HN group (210.7 +/- 73.8 seconds; P
      =.003). Fluid used for lens substance removal was significantly less in the HY
      (91.0 +/- 47.5 ml) than in the HN group (156.9 +/- 87.2 ml; P <.001). In the HY
      group, lens substance removal was ranked as easy in 36 eyes (90.0%), average in 2
      eyes (5.0%), and difficult in 2 eyes (5.0%). In the HN group, removal was easy in
      19 eyes (47.5%), average in 12 eyes (30.0%), difficult in 5 eyes (12.5%), and
      very difficult in 4 (10.0%) eyes (P =.0005). Residual cortical fibers on the
      posterior capsule were noted in 12.5% of the HY group and 22.5% of HN group, but
      the difference was not statistically significant (P =.2). CONCLUSIONS:
      Multiquadrant cortical-cleaving hydrodissection decreases lens substance removal
      time, lessens fluid volume used for lens substance removal, and facilitates lens
      substance removal in pediatric cataract surgery.

PMID- 12504703
TI  - Clinico-microbiological correlation of suture-related graft infection following
      penetrating keratoplasty.
AB  - PURPOSE: To report the clinical and microbiological profiles of suture-related
      graft infections following penetrating keratoplasty. DESIGN: Interventional case
      series. METHODS: The medical and microbiology records of all patients who
      presented with suture-related graft infections and were seen between January 1999
      and December 2001 were reviewed. RESULTS: Of 105 patients (105 eyes) who
      developed corneal infiltrates following penetrating keratoplasty, 37 patients (24
      optical and 13 therapeutic) were identified as having suture-related graft
      infection. The median onset of infiltrates after penetrating keratoplasty was 87
      days for 31 patients who presented within one year. Gram-stained smears of
      corneal scrapings were positive in 27 (73%) of 37 patients, whereas cultures were
      positive in 32 (only bacteria, 30; mixed bacteria and fungi, 2). Thirty-seven
      isolates were obtained from 32 patients (gram-positive bacteria, 32; gram
      negative bacteria, 3; fungus, 2). All gram-positive isolates were sensitive to
      cefazolin, chloramphenicol, and vancomycin, whereas one of three gram-negative
      isolates (Pseudomanas species) was resistant to all the antibiotics tested. Of 32
      patients, 30 (82%) responded satisfactorily to medical management. CONCLUSIONS:
      Suture-related graft infections are usually caused by bacteria that are sensitive
      to ciprofloxacin, cefazolin, and gentamicin, and the patients respond
      satisfactorily to medical therapy.

PMID- 12504704
TI  - Penetrating corneal transplant with inadvertent corneal button inversion.
AB  - PURPOSE: To report a penetrating corneal transplant in which there was
      inadvertent inversion of the corneal button. DESIGN: Interventional case report.
      METHODS: A 48-year-old man with lattice corneal dystrophy had a third penetrating
      keratoplasty in the right eye 3 years after the second procedure and 2 years
      following renal transplantation. RESULTS: Histologic examination of the corneal
      button from the second penetrating keratoplasty disclosed inadvertent corneal
      graft inversion. Survival epithelium from the donor in the anterior chamber may
      be explained by the ocular anterior chamber-associated immune deviation or by the
      patient's systemic cyclosporine A (CsA) treatment after renal transplantation.
      CONCLUSIONS: Histologically proven corneal button inversion is a rare cause of
      corneal graft failure.

PMID- 12504705
TI  - Tuberculous granuloma managed by full thickness eye wall resection.
AB  - PURPOSE: To report the use of eye wall resection in the management of tuberculous
      granuloma. DESIGN: Interventional case report. METHODS: In a 26-year-old man with
      biopsy-proven tuberculous granuloma of the left eye, total eye wall resection and
      donor scleral grafting was performed for management of tuberculous granuloma
      involving the sclera, part of the cornea, the iris, the chamber angle, and the
      ciliary body. Adjuvant therapy included oral antitubercular medication. RESULTS:
      The treatment of the infection was successful. The scleral graft healed well, and
      the crystalline lens was preserved. CONCLUSIONS: Total eye wall resection, a
      technique described in the management of uveal tumors, can be adopted to manage
      selected cases of tuberculous granuloma of the eye.

PMID- 12504706
TI  - Bilateral optic nerve infiltration in central nervous system leukemia.
AB  - PURPOSE: To report the case of a 58-year-old man with sequential bilateral
      retrolaminar leukemic infiltration of the optic nerves who presented with normal
      appearing optic nerves and no optic nerve enhancement. DESIGN: Interventional
      case report. METHODS: A 58-year-old man with chronic myelogenous leukemia (CML)
      developed progressive vision loss to no light perception in both eyes over four
      days. The patient received 14 doses of external beam irradiation and 10 cycles of
      intrathecal cytarabine. Despite treatment, he developed optic nerve pallor, and
      visual acuity remained no light perception in both eyes. CONCLUSIONS: In a
      patient with leukemia, leukemic optic nerve infiltration may occur even with
      normal-appearing optic nerves and a normal magnetic resonance image. It is
      important to maintain a high clinical suspicion for optic nerve infiltration so
      that prompt local irradiation may be initiated.

PMID- 12504707
TI  - Acute occipital demyelinating lesion appearing as an infarct on diffusion
      magnetic resonance imaging.
AB  - PURPOSE: To report a case of a 27-year-old woman who presented with an acute
      right homonymous visual field deficit due to demyelination diagnosed by
      postprocessing analysis of the magnetic resonance imaging (MRI). DESIGN:
      Observational case report. METHODS: Magnetic resonance imaging analysis with an
      exponential diffusion-weighted imaging. RESULTS: On MRI, a left occipital lesion
      with mild enhancement after gadolinium infusion on the T1-weighted image, bright
      signal with some mass effect on the T2-weighted image, and the diffusion-weighted
      imaging suggested a diagnosis of an acute infarct. With the use of the
      exponential image technique, the T2 hyperintense signal present on the diffusion
      study was almost completely eliminated, changing the diagnosis and treatment
      plan. Subsequent examinations and MRI confirmed the diagnosis of demyelinating
      disease. CONCLUSIONS: In diseases such as cerebral ischemia and demyelination,
      MRI diffusion is often abnormal because such diseases modify the integrity of
      central nervous system structures. A technique that subtracts the T2 contribution
      to the diffusion-weighted imaging analysis supported a diagnosis of an acute
      demyelinating episode that was subsequently confirmed.

PMID- 12504708
TI  - Intramuscular hydatid cyst of the medial rectus muscle.
AB  - PURPOSE: To describe a unique case of orbital hydatid cyst that was located
      solely within the medial rectus muscle. DESIGN: Retrospective, interventional
      case report. METHODS: A 20-year-old woman presented with right periocular pain
      induced by ocular movements. Magnetic resonance imaging studies showed a focal,
      well-circumscribed intramuscular cystic lesion of the right medial rectus muscle.
      The cyst was completely extirpated from the muscle, but some of the fluid content
      escaped into the surrounding tissues. Irrigation with hypertonic saline was
      performed. RESULTS: Histopathologic examination showed an acellular cyst wall
      with inner germinal layer, diagnostic for hydatid cyst. Two cycles of oral
      albendazole were administered with no recurrence. CONCLUSIONS: In the orbit,
      hydatid cyst may be localized primarily within an extraocular muscle and produce
      painful eye movements. Hydatid cyst must be considered in the differential
      diagnosis of solitary cystic enlargements of extraocular muscles.

PMID- 12504709
TI  - Visual field indexes for version 3.0 of frequency doubling perimetry in patients
      with glaucoma.
AB  - PURPOSE: A new version of frequency doubling perimetry was compared to a former
      version in patients with glaucoma. DESIGN: Prospective observational study.
      METHOD: Thirty-two patients with glaucoma were examined twice sequentially in one
      eye with threshold c-20 of frequency doubling perimetry version 2.6. Within 3
      months, the same eye was again examined twice sequentially, this time using the
      new version 3.0. Mean deviation, pattern standard deviation, short-term
      fluctuation, intraocular pressure at examination, and test duration were compared
      between versions. RESULTS: No significant difference was found in mean deviation,
      pattern standard deviation, intraocular pressure, or short-term fluctuation
      between versions. CONCLUSIONS: Version 3.0 took less time to perform the
      threshold test than did version 2.6. Version 3.0 of the frequency doubling
      perimetry program took less time to perform and showed similar values of visual
      field indexes when compared with version 2.6.

PMID- 12504710
TI  - Transient, profound cataract associated with intracameral 5-fluorouracil.
AB  - PURPOSE: To report a transient cataract after bleb needling and subconjunctival
      injection of 5-fluorouracil. DESIGN: Observational case report. METHODS: A 51
      year-old man had an encapsulated bleb after filtering surgery. The bleb was
      needled, and 5 mg of 5-fluorouracil was injected adjacent to the bleb. RESULTS:
      Within 5 minutes, vision fell to finger counting at 1 foot owing to anterior lens
      capsule opacification. The next day, acuity and lens clarity had returned to
      their preneedling status. Best-corrected acuity 7 months later was 20/15.
      CONCLUSION: Entry of 5-fluorouracil into the anterior chamber after bleb needling
      can cause transient lens opacification. Recently, intracameral 5-fluorouracil was
      reported as a new treatment for epithelial ingrowth. Given the transient cataract
      observed in this case, the use of 5-fluorouracil for epithelial ingrowth should
      be considered with caution for phakic patients.

PMID- 12504711
TI  - A paradoxical ocular effect of brimonidine.
AB  - PURPOSE: We report an unusual paradoxical effect of brimonidine. DESIGN:
      Observational case report. METHODS: A 70-year-old woman with bilateral normal
      tension glaucoma was treated with topical brimonidine and followed in an
      outpatient setting. The main outcome measured was intraocular pressure (IOP) in
      mm Hg. RESULTS: Brimonidine was observed to cause IOP elevation, confirmed on
      rechallenge, scoring 8 (strong probability) on an adverse drug reaction
      probability score. CONCLUSION: Under certain circumstances topical brimonidine
      can cause paradoxical raised IOP necessitating vigilance in follow-up of patients
      on topical brimonidine.

PMID- 12504712
TI  - Acute multifocal placoid pigment epitheliopathy-like lesion as an early
      presentation of subacute sclerosing panencephalitis.
AB  - PURPOSE: To report a case of acute multifocal placoid pigment epitheliopathy
      (AMPPE)-like lesion as an early presentation of subacute sclerosing
      panencephalitis (SSPE). DESIGN: Observational case report. METHODS: A 21-year-old
      woman presented with a profound loss of vision in the left eye. The initial
      clinical picture was characterized by a whitish infiltration of the macular area
      and papillary edema in the left eye. Six days later multiple chorioretinal
      infiltrations were present in the peripheral fundus of the left eye, which led to
      the diagnosis of AMPPE. RESULTS: During the following year, a gradual change in
      her personality developed. The diagnosis of SSPE was made by cerebrospinal fluid
      examination. Her clinical condition deteriorated rapidly, and she died.
      CONCLUSIONS: AMPPE can be accompanied by central nervous system involvement. We
      wish to emphasize the importance of considering the diagnosis of SSPE in cases of
      AMPPE.

PMID- 12504713
TI  - Modified technique to create retinal detachment during macular translocation
      surgery.
AB  - PURPOSE: To report a modified technique for creating total retinal detachment
      during macular translocation surgery with a 360-degree retinotomy. DESIGN:
      Interventional case series. METHODS: After vitrectomy, BSS Plus (Alcon, Fort
      Worth, TX, USA) was injected into the subretinal space with a 39-gauge needle to
      create a small retinal detachment. The tip of a 20-gauge silicone-tipped needle
      was then placed in the hole created by the needle, and BSS Plus was injected
      subretinally at a high flow rate. RESULTS: In 10 eyes (10 patients), we created
      one iatrogenic retinal hole in seven eyes and two holes in three eyes. The time
      needed to create total retinal detachment was decreased. CONCLUSIONS: Our
      technique seems to make creation of a total retinal detachment easier compared
      with the previous standard procedure and may reduce postoperative complications
      following macular translocation surgery with a 360-degree retinotomy.

PMID- 12504714
TI  - Interlenticular opacification associated with asymmetric haptic fixation of the
      anterior intraocular lens.
AB  - PURPOSE: To describe the occurrence of interlenticular opacification in
      association with asymmetric haptic fixation of the anterior intraocular lens in a
      patient who had two intraocular lenses (IOLs) inserted for axial hyperopia.
      DESIGN: Observational case report. METHODS: An 83-year-old patient underwent
      uncomplicated cataract extraction and piggyback IOL insertion. The posterior IOL
      was placed within the capsule, but one of the haptics of the anterior IOL was
      inadvertently placed in the ciliary sulcus and the other in the capsule. RESULTS:
      Interlenticular opacification was localized to the interlenticular area near the
      anterior lens haptic placed within the capsule and absent from the
      interlenticular area near the anterior lens haptic fixated in the ciliary sulcus.
      CONCLUSION: This case report supports the idea that sulcus placement of the
      anterior IOL helps to prevent interlenticular opacification.

PMID- 12504715
TI  - Limited macular translocation for the management of subfoveal choroidal
      neovascularization after photodynamic therapy.
AB  - PURPOSE: To report our initial experience of limited macular translocation in
      patients with subfoveal choroidal neovascularization secondary to age-related
      macular degeneration following photodynamic therapy with verteporfin. DESIGN:
      Interventional case series. METHODS: Retrospective review of four eyes of four
      consecutive patients with subfoveal choroidal neovascularization secondary to age
      related macular degeneration who underwent effective limited macular
      translocation following photodynamic therapy. The mean logarithm of minimal angle
      of resolution preoperative best-corrected visual acuity was 20/190 (range, 20/150
      to 20/200), and in all eyes the visual acuity was 20/150 or worse. The major
      outcome measures were postoperative visual acuity and complications related to
      the surgery. RESULTS: The mean postoperative follow-up was 6.75 months (range, 6
      8 months). Postoperative best-corrected visual acuity improved by 2 or more
      Snellen lines of visual acuity in three of four eyes (75%) and remained within 1
      line in one of four eyes (25%). The mean postoperative best-corrected visual
      acuity was 20/100 (range, 20/40 to 20/150), and in two of the four eyes (50%) the
      visual acuity achieved was 20/100 or better. No complication was observed.
      CONCLUSIONS: Limited macular translocation may be a viable option in patients who
      have previously undergone photodynamic therapy.

PMID- 12504716
TI  - Foveal hypoplasia demonstrated in vivo with optical coherence tomography.
AB  - PURPOSE: We demonstrate foveal hypoplasia by optical coherence tomography (OCT).
      DESIGN: Observational case report. METHODS: Foveal hypoplasia was demonstrated in
      a 79-year-old man with decreased vision since childhood using fundus photography,
      fluorescein angiography, and OCT scans through four meridians of the central
      foveal. RESULTS: The OCT showed extension of all neurosensory retinal layers
      through the area in which the fovea would normally be located. CONCLUSION:
      Optical coherence tomography can be used to demonstrate foveal hypoplasia.

PMID- 12504717
TI  - Photodynamic therapy for choroidal neovascularization after thermal laser
      photocoagulation for diabetic macular edema.
AB  - PURPOSE: To report the use of photodynamic therapy for treating a choroidal
      neovascular membrane secondary to thermal laser photocoagulation. DESIGN:
      Interventional case report. METHODS: A 61-year-old man with a choroidal
      neovascular membrane secondary to thermal laser photocoagulation for diabetic
      macular edema was treated with photodynamic therapy. RESULTS: Subjective and
      objective improvement in visual acuity and improvement of fluorescein angiogram
      have been demonstrated for more than a year after treatment. CONCLUSIONS:
      Photodynamic therapy may be useful for treating patients with choroidal
      neovascularization secondary to thermal laser photocoagulation.

PMID- 12504718
TI  - Resolution of diabetic cystoid macular edema associated with spontaneous
      vitreofoveal separation.
AB  - PURPOSE: To report spontaneous resolution of diabetic cystoid macular edema (CME)
      associated with spontaneous vitreofoveal separation. DESIGN: Interventional case
      series. METHODS: Optical coherence tomography (OCT) was performed on three eyes
      of three diabetic patients with CME before and after vitreofoveal separation.
      RESULTS: In all three eyes, OCT showed cystic changes at the fovea with a
      slightly detached posterior hyaloid, which remained attached to the optic disk
      and the fovea. After spontaneous separation of the hyaloid at the fovea, there
      was resolution of the cystic cavities and restoration of the foveal depression.
      CONCLUSIONS: In some eyes of diabetic patients, CME is caused by a vitreous
      traction. Resolution of CME may occur after spontaneous vitreofoveal separation.

PMID- 12504719
TI  - Extensive dynamics in location, shape, and size of aneurysms in a patient with
      idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome.
      Idiopathic retinal vasculitis, aneurysms, and neuroretinitis.
AB  - PURPOSE: To describe an unusual case of idiopathic retinal vasculitis, aneurysms,
      and neuroretinitis (IRVAN) syndrome with rapid dynamics in the number and
      appearance of the aneurysms. DESIGN: Observational case report. METHODS: Clinical
      and angiographic data of the patient were reviewed. RESULTS: In the course of
      only 6 months, preexisting retinal aneurysms resolved while new ones appeared.
      Changes were observed in the shape and size of preexisting lesions. The
      resolution of lesions in eyes previously untreated by laser is reported for the
      first time. CONCLUSIONS: Vascular lesions in IRVAN syndrome may show an unusually
      rapid turnover. The resolution of aneurysms is a part of the natural course of
      the disease and may occur without previous retinal laser photocoagulation.

PMID- 12504720
TI  - Foveal congenital hypertrophy of the retinal pigment epithelium in the setting of
      geographic atrophy from age-related macular degeneration.
AB  - PURPOSE: To report a case of presumed congenital hypertrophy of the retinal
      pigment epithelium in the fovea of an 88-year-old woman in the setting of
      geographic atrophy from age-related macular degeneration. DESIGN: Observational
      case report. METHODS: An 88-year-old woman was examined. RESULTS: Best-corrected
      visual acuity was 20/63 in the right eye and 20/50 in the left eye. Multifocal
      areas of geographic atrophy and large-sized drusen were seen in the maculae of
      both eyes. Biomicroscopic examination of the right eye showed hyperpigmentation
      consistent with congenital hypertrophy of the retinal pigment epithelium through
      the center of the macula. No prior photographic documentation of the retina was
      available. CONCLUSION: This case suggests that foveal congenital hypertrophy of
      the retinal pigment epithelium may be seen in the setting of macular geographic
      atrophy. Although it is theoretically possible that the hyperpigmentation is
      reactive rather than congenital, the pigmentation is typical for congenital
      hypertrophy and is unlike any reactive pigmentation in our experience or
      described in a MEDLINE search of features of age-related macular degeneration.
      The case suggests that a hypertrophic process of the retinal pigment epithelium
      may coexist within or immediately adjacent to the anatomic boundaries of an
      atrophic process such as geographic atrophy from age-related macular
      degeneration.

PMID- 12504721
TI  - Topical mitomycin C for conjunctival-corneal squamous cell carcinoma.

PMID- 12504723
TI  - Clinical observations supporting a theoretical model of choriocapillaris blood
      flow in treatment of choroidal neovascularization.

PMID- 12504737
TI  - Optic disk drusen.
AB  - Optic disk drusen occur in 3.4 to 24 per 1,000 population and are bilateral in
      approximately 75%. Disturbance in the axonal metabolism in the presence of a
      small scleral canal--regardless of eyelength--is considered responsible for the
      development. The drusen increase in size, becoming more visible with age due to
      continuing calcium apposition, and they are associated with visual field defects
      in a considerable number of patients. Patients do not usually notice these
      defects, despite their progressive nature over the years, and this indicates an
      insidious course. A correct diagnosis of optic disk drusen is mandatory, although
      effective treatment is not yet available. It is most important to differentiate
      optic disk drusen from papilledema in order to avoid unnecessary neurological
      examinations, but also to avoid overlooking genuine neurologic disorders. Because
      optic disk drusen can cause severe visual field defects, patients require
      individual consultation regarding work issues and whether or not to drive. Optic
      disk drusen can be accompanied by vascular complications as well. In some cases
      these vascular changes--for example, choroidal neovascularization--are treatable.
      Patients with optic disk drusen should undergo regular visual field, IOP, and
      nerve fiber layer examinations. In patients with deteriorating visual field and
      borderline IOP, we recommend antiglaucomatous therapy.

PMID- 12504738
TI  - Night vision disturbances after corneal refractive surgery.
AB  - A certain percentage of patients complain of "glare" at night after undergoing a
      refractive surgical procedure. When patients speak of glare they are,
      technically, describing a decrease in quality of vision secondary to glare
      disability, decreased contrast sensitivity, and image degradations, or more
      succinctly, "night vision disturbances." The definitions, differences, and
      methods of measurement of such vision disturbances after refractive surgery are
      described in our article. In most cases of corneal refractive surgery, there is a
      significant increase in vision disturbances immediately following the procedure.
      The majority of patients improve between 6 months to 1 year post-surgery. The
      relation between pupil size and the optical clear zone are most important in
      minimizing these disturbances in RK. In PRK and LASIK, pupil size and the
      ablation diameter size and location are the major factors involved. Treatment
      options for disabling glare are also discussed. With the exponential increase of
      patients having refractive surgery, the increase of patients complaining of
      scotopic or mesopic vision disturbances may become a major public health issue in
      the near future. Currently, however, there are no gold-standard clinical tests
      available to measure glare disability, contrast sensitivity, or image
      degradations. Standardization is essential for objective measurement and follow
      up to further our understanding of the effects of these surgeries on the optical
      system and thus, hopefully, allow for modification of our techniques to decrease
      or eliminate post-refractive vision disturbances.

PMID- 12504739
TI  - Myocilin glaucoma.
AB  - Genetic factors have long been implicated in the pathophysiology of primary open
      angle glaucoma (POAG). Recently, myocilin, a gene of unknown function, was
      associated with both juvenile open-angle glaucoma (JOAG) and POAG. Forty-three
      different myocilin mutations have been reported in open-angle glaucoma patients,
      and several large studies have suggested that as a group these mutations are
      associated with 3-4% of POAG in patient populations worldwide. Support for the
      pathogenicity of the individual myocilin mutations has been obtained from in
      vitro assays, statistical methods, and conservation of gene sequence arguments.
      Several of these myocilin mutations were observed in multiple patients allowing
      the identification of mutation-specific glaucoma phenotypes (maximum intraocular
      pressure and age at diagnosis). Associations between myocilin and other forms of
      open-angle glaucoma have been explored. At present there is no evidence to link
      myocilin mutations and steroid-induced ocular hypertension or normal-tension
      glaucoma. Clinical vignettes of POAG patients from four generations of a family
      harboring the TYR437HIS myocilin mutation are presented, highlighting the
      benefits of elucidating the genetics of glaucoma.

PMID- 12504740
TI  - Functional magnetic resonance imaging and its clinical utility in patients with
      visual disturbances.
AB  - Functional magnetic resonance imaging (fMRI) is a powerful, non-invasive
      technique for mapping human brain function. Because of the robust signal
      intensity changes associated with visual stimuli, fMRI is particularly useful for
      studying visual cortex (including both striate and extrastriate cortex). Also,
      activation of the lateral geniculate nuclei has been successfully demonstrated by
      fMRI. Therefore, fMRI may be potentially useful in patients with visual deficits
      by providing a non-invasive method for assessing the afferent visual pathways and
      higher cortical areas. Although there have been several reviews on fMRI, few have
      highlighted its clinical applicability in patients with visual disturbances. Our
      article will review fMRI principles and methodology, then focus on the possible
      applications and limitations of this technique in clinical ophthalmology.

PMID- 12504741
TI  - Multimodal macula mapping: a new approach to study diseases of the macula.
AB  - Multimodal macula mapping is presented as a combination of a variety of
      diagnostic tools and techniques to examine the macular region in order to obtain
      information on its structure and function in a clinical environment. Foundations
      of macular mapping are reviewed and discussed. New methodologies for multimodal
      macula mapping based on a combination of scanning laser angiography, retinal
      leakage analysis, retinal thickness analysis, and visual field testing are
      presented, demonstrating the potential of macula mapping. Other available
      detection devices are briefly reviewed considering their potential to be included
      and utilized in future developments of multimodal macula mapping. Multimodal
      macula mapping appears to offer unique perspectives and insights that are
      expected to contribute to improved diagnosis and better understanding of macular
      diseases.

PMID- 12504742
TI  - Bilateral retinal hemorrhages in an 18-year-old woman.
AB  - A previously healthy 18-year-old woman presented with sudden onset of central
      blurred vision in the right eye. Fundoscopic examination showed retinal venous
      tortuosity, several flame-shaped hemorrhages bilaterally, and a subhyaloid
      hemorrhage in the right fovea. Laboratory evaluation and subsequent bone marrow
      biopsy were consistent with the diagnosis of acute lymphoblastic leukemia. The
      retinal findings had cleared almost completely by three weeks after initiation of
      chemotherapy.

PMID- 12504743
TI  - An unusual junctional scotoma.
AB  - A 28-year-old woman presented with painful unilateral left visual loss, impaired
      color vision, left afferent pupillary defect, and normal ocular fundus. Although
      optic neuritis was first suspected, visual fields disclosed a junctional scotoma
      related to chiasmal demyelination, due to a probable multiple sclerosis.

PMID- 12504747
TI  - Diabetic papillopathy and nonarteritic anterior ischemic optic neuropathy.

PMID- 12504750
TI  - The in vivo but not the in vitro am3 revertant frequencies increase linearly with
      increased ethylnitrosourea doses in spleen of mice transgenic for phiX174 am3,
      cs70 using the single burst assay.
AB  - The am3 revertant frequencies (RF) in spleens from male mice transgenic for
      phiX174 am3, cs70 were analyzed 14 weeks after ethylnitrosourea (ENU) treatment,
      both by the single burst assay (SBA) and the mixed burst assay (MBA). The mean in
      vivo (burst size >30/assay plate) revertant frequency (MRF) for the vehicle
      control was 2.6x10(-7). The ENU induced in vivo RF were linear over the dose
      range 0-150mg/kg, (r(2)=0.999). The concomitant in (burst size <or=30/assay
      plate) was independent of dose (r(2)=0.216). The only viable revertants are base
      pair substitutions of the center base pair in the am3 nonsense (TAG) codon in the
      phiX174 lysis E gene. Sequenced revertants chosen randomly from in vitro plates
      and in vivo untreated control plates were A-->G transitions. Sequence analysis of
      in vivo revertants from ENU treated animals revealed revertants that were 17% A-
      >G transitions and 83% A-->T transversions, the latter being consistent with the
      reported A:T base pair alterations induced by ENU. No A-->C transitions were
      seen. This suggests the occurrence of an ENU-induced O(2) ET-dT lesion leading to
      a dT base mismatch. The observations in this report both confirm and validate the
      use of the SBA for distinguishing between in vivo mutations that are fixed in the
      animal and in vitro mutations that arise from other sources. The ability of the
      SBA to distinguish the in vivo from the in vitro origin of mutations has
      increased the specificity, sensitivity and utility of the phiX transgenic system.

PMID- 12504751
TI  - A cross-platform public domain PC image-analysis program for the comet assay.
AB  - The single-cell gel electrophoresis, also known as the comet assay, has gained
      wide-spread popularity as a simple and reliable method to measure genotoxic and
      cytotoxic effects of physical and chemical agents as well as kinetics of DNA
      repair. Cells are generally stained with fluorescent dyes. The analysis of comets
      -damaged cells which form a typical comet-shaped pattern--is greatly facilitated
      by the use of a computer image-analysis program. Although several image-analysis
      programs are available commercially, they are expensive and their source codes
      are not provided. For Macintosh computers a cost-free public domain macro is
      available on the Internet. No ready for use, cost-free program exists for the PC
      platform. We have, therefore, developed such a public domain program under the
      GNU license for PC computers. The program is called CASP and can be run on a
      variety of hardware and software platforms. Its practical merit was tested on
      human lymphocytes exposed to gamma-rays and found to yield reproducible results.
      The binaries for Windows 95 and Linux, together with the source code can be
      obtained from: http://www.casp.of.pl.

PMID- 12504752
TI  - Potential value of the comet assay and DNA adduct measurement in dab (Limanda
      limanda) for assessment of in situ exposure to genotoxic compounds.
AB  - An in situ study of the relationship between marine contamination and genotoxic
      effects was performed on female dab (Limanda limanda) collected from different
      sites in the eastern English Channel (France) known to be contaminated by
      polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs). DNA
      adducts in liver and DNA strand breaks in blood cells were determined
      respectively by the nuclease P1-enhanced post-labelling technique and an alkaline
      version of the comet assay. The extent of DNA base oxidation was also assessed
      for three of the six sampling sites in the study, using a comet assay in
      combination with a specific DNA repair enzyme, formamidopyrimidine glycosylase
      (Fpg).With Comet data, two groups of sites that seem in accordance with the
      pollution level have been distinguished. The extent of DNA strand breaks was
      higher in adult than juvenile female dab. From a technical point of view, comet
      assay sensitivity was affected by high intra-individual variability that
      accounted for nearly 70% of total variance (the site factor represented no more
      than 26%). The combined use of the comet assay and Fpg showed the presence of DNA
      oxidised bases in environmentally exposed dab.Although qualitative differences
      between the sampling sites were observed in DNA adduct profiles, no significant
      differences were found for total DNA adduct levels. DNA adducts did not appear to
      be associated with PAH exposure. Histopathological studies showed hepatic
      steatosis in most of the animals examined. Only one pre-cancerous lesion (an
      early stage of hyperplasia) was detected (associated frequency of 0.8%).

PMID- 12504753
TI  - Assessment of genotoxic effect of benzo[a]pyrene in endotracheally treated rat
      using the comet assay.
AB  - Although benzo[a]pyrene (B[a]P) is a well-known genotoxic agent, little is known
      about the extent of DNA effects induced by B[a]P in rat tissues after pulmonary
      exposure. The alkaline single-cell gel electrophoresis (comet assay) was used to
      measure DNA single-strand breaks in alveolar macrophages, lung cells, peripheral
      lymphocytes and hepatocytes of OFA Sprague-Dawley rats exposed to a single dose
      of B[a]P by endotracheal administration. Statistically significant damage was
      observed in all organs tested after 3, 24 and 48h of pulmonary exposure to 3mg of
      B[a]P per animal, with a time-dependent relationship. The maximum damage was
      observed in the four cell types 24h after exposure. The higher level of damage
      was observed both in lung cells and peripheral lymphocytes; in alveolar
      macrophages and hepatocytes the level of damage was increased, but at a lower
      level than in the two other cell types. Furthermore, B[a]P demonstrated a clear
      dose-related genotoxic activity in the lung cells when tested at doses of 0.75,
      1.5 and 3mg. The current study shows that B[a]P caused DNA single-strand breaks
      in the respiratory tract of endotracheally treated OFA Sprague-Dawley rats. The
      study also suggests that pulmonary exposure to B[a]P can induce a high level of
      DNA damage in peripheral lymphocytes. The clear relationship between lung
      exposure to B[a]P and consequences observed in lymphocytes suggests that the
      comet assay in peripheral lymphocytes can be used as a sensitive marker in human
      monitoring studies.

PMID- 12504754
TI  - Intra- and inter-laboratory variation in the scoring of micronuclei and
      nucleoplasmic bridges in binucleated human lymphocytes. Results of an
      international slide-scoring exercise by the HUMN project.
AB  - One of the objectives of the HUman MicroNucleus (HUMN) project is to identify the
      methodological variables that have an important impact on micronucleus (MN) or
      micronucleated (MNed) cell frequencies measured in human lymphocytes using the
      cytokinesis-block micronucleus assay. In a previous study we had shown that the
      scoring criteria used were likely to be an important variable. To determine the
      extent of residual variation when laboratories scored cells from the same
      cultures using the same set of standard scoring criteria, an inter-laboratory
      slide-scoring exercise was performed among 34 laboratories from 21 countries with
      a total of 51 slide scorers involved. The results of this study show that even
      under these optimized conditions there is a great variation in the MN frequency
      or MNed cell frequency obtained by individual laboratories and scorers. All
      laboratories ranked correctly the MNed cell frequency in cells from cultures that
      were unirradiated, or exposed to 1 or 2Gy of gamma rays. The study also estimated
      that the intra-scorer median coefficient of variation for duplicate MNed cell
      frequency scores is 29% for unexposed cultures and 14 and 11% for cells exposed
      to 1 and 2Gy, respectively. These values can be used as a standard for quality or
      acceptability of data in future studies. Using a Poisson regression model it was
      estimated that radiation dose explained 67% of the variance, while staining
      method, cell sample, laboratory, and covariance explained 0.6, 0.3, 6.5, and
      25.6% of the variance, respectively, leaving only 3.1% of the variance
      unexplained. As part of this exercise, nucleoplasmic bridges were also estimated
      by the laboratories; however, inexperience in the use of this biomarker of
      chromosome rearrangement was reflected in the much greater heterogeneity in the
      data and the unexplained variation estimated by the Poisson model. The results of
      these studies indicate clearly that even after standardizing culture and scoring
      conditions it will be necessary to calibrate scorers and laboratories if MN, MNed
      cell and nucleoplasmic bridge frequencies are to be reliably compared among
      laboratories and among populations.

PMID- 12504755
TI  - HUMN project: detailed description of the scoring criteria for the cytokinesis
      block micronucleus assay using isolated human lymphocyte cultures.
AB  - Criteria for scoring micronuclei and nucleoplasmic bridges in binucleated cells
      in the cytokinesis-block micronucleus assay for isolated human lymphocyte
      cultures are described in detail. Morphological characteristics of mononucleated
      cells, binucleated cells, and multinucleated cells as well as necrotic and
      apoptotic cells and nuclear buds are also described. These criteria are
      illustrated by a series of schematic diagrams as well as a comprehensive set of
      colour photographs that are of practical assistance during the scoring of slides.
      These scoring criteria, diagrams and photographs have been used in a HUman
      MicronNucleus (HUMN) project inter-laboratory slide-scoring exercise to evaluate
      the extent of variability that can be attributable to individual scorers and
      individual laboratories when measuring the frequency of micronuclei and
      nucleoplasmic bridges in binucleated cells as well as the nuclear division index.
      The results of the latter study are described in an accompanying paper. It is
      expected that these scoring criteria will assist in the development of a
      procedure for calibrating scorers and laboratories so that results from different
      laboratories for the cytokinesis-block micronucleus assay may be more comparable
      in the future.

PMID- 12504756
TI  - Induction of poly(ADP-ribosyl)ation and DNA damage in human peripheral
      lymphocytes after treatment with (-)-epigallocatechin-gallate.
AB  - With regard to a future use of tea polyphenols in intervention trials with
      individuals at high cancer risk, the effects of the tea ingredient (-)
      epigallocatechin gallate (EGCG) on poly(ADP-ribose) (PAR) levels and on DNA
      damage were investigated in human lymphocytes. A dose- and time-dependent
      elevation of both PAR formation as assessed by quantitative immunofluorescence
      analysis and DNA damage as assessed by the comet assay were observed after
      treatment with EGCG at 20, 40 and 80 microM for 10-240 min. Maximum levels of PAR
      formation and of DNA damage were observed after 10 min at all concentrations
      tested. Increased PAR levels were still detectable by 240 min in the 40 and 80
      microM groups. At the lowest concentration, which is near the physiological peak
      values found after tea ingestion, PAR formation was not correlated with DNA
      damage. Here, EGCG led to pronounced PAR levels, whereas the comet assay was
      almost negative. In contrast, such marked differences in time course and extent
      of both genotoxicity and PAR formation following EGCG treatment were not detected
      after gamma-irradiation. Our results suggest that the known chemopreventive
      effects of EGCG, the main constituent of tea, may be partly attributed to an
      induction of PAR formation.

PMID- 12504757
TI  - Statistical evaluation and comparison of comet assay results.
AB  - A method of critical evaluation of comet assay test results is proposed. This
      method is based on representing frequency histograms of tail moments and %DNA in
      the tail with the use of the unsymmetrical Weibull distribution. The distribution
      is fully characterized by two parameters: shape (alpha) and scale (beta).
      Coefficients of variation and confidence intervals of the parameters have been
      determined.

PMID- 12504758
TI  - Evaluation of the genotoxic potential of lambda-cyhalothrin using nuclear and
      nucleolar biomarkers on fish cells.
AB  - Micronucleus formation in fish erythrocytes, as an indicator of chromosomal
      damage, has been increasingly used to detect the genotoxic potential of
      environmental contaminants. Nucleolar organizer regions (NORs) stained with
      colloidal silver techniques indicate sites of active RNA transcription. The
      number and size of NORs in interphase nuclei reflect cellular activities such as
      proliferation and differentiation of cells. In this study, nuclear (micronucleus
      frequency) and nucelolar (changes in quantitative characteristics of nucleoli)
      biomarkers were used to evaluate the functional and structural genotoxic effects
      of the pyrethroid insecticide lambda-cyhalothrin on Garra rufa (Pisces:
      Cyprinidae). The frequency of micronuclei was examined in blood smears obtained
      from fishes exposed to three different concentrations (0.005, 0.01, 0.05
      microg/l) for a period of 36 h. Nucleolar parameters (the average number of
      nucleoli per cell; the volume of a single nucleolus; and the percentage of cells
      with heteromorphic paired nucleoli) were examined in epithelial cells obtained
      from the edge of caudal fins at the 90th and 180th minutes of exposure. Results
      of both tests demonstrated the genotoxic potential of pyrethroid lambda
      cyhalothrin on G. rufa. The frequency of micronucleated erythrocytes was
      significantly increased while the nucleolar parameters were repressed by lambda
      cyhalothrin treatment. Our results confirmed that the use of nucleolar biomarkers
      on fish fin cells, in addition to micronucleus test, could provide valuable
      information in aquatic genotoxicity studies.

PMID- 12504759
TI  - Mutagenic characteristics of river waters flowing through large metropolitan
      areas in North America.
AB  - The hanging technique using blue rayon, which specifically adsorbs mutagens with
      multicyclic planar structures, has the advantages over most conventional methods
      of not having to bring large volumes of water back to the laboratory for
      extraction of organic materials. Therefore, for the same effort the hanging blue
      rayon technique allows for the analysis of more samples from remote sites,
      although it has a disadvantage of not allowing quantitative analysis. In this
      study, the blue rayon hanging technique was used to collect organic mutagens in
      river waters that flow through metropolitan areas in northeastern North America.
      Monitoring was performed at a total of 21 sites: the Providence River system (4
      sites), the Charles River (2 sites), the Potomac River (6 sites), the St.
      Lawrence River (5 sites), the Hudson River (3 sites), and the East River (1
      site). Mutagenicity was evaluated using the Salmonella assay with strains TA98,
      TA100, YG1024, YG1041, and YG1042 with and without metabolic activation. The
      results demonstrated that strains YG1041 and YG1024 were much more sensitive than
      TA98 with S9 mix. Fifteen samples out of 21 were positive in YG1041 with S9 mix.
      Six samples gave 5000-18,400 revertants/g blue rayon equivalent. YG1042 was also
      much more sensitive than TA100. Eight samples were positive in YG1042 with S9
      mix. The highest activity was 10,200 revertants/g blue rayon equivalent. The
      overall results showed that rivers flowing through major cities in North America
      contain frameshift-type, aromatic amine-like mutagenic activity. However, the
      levels of mutagenic activity in these rivers were much lower than expected based
      on prior analyses and calculated population-to-discharge ratios. Further
      research, such as detailed chemical analyses and/or simultaneous comparisons of
      several different adsorbents (e.g. XAD and blue rayon), will be needed to clarify
      the observed differences between North American blue rayon values and published
      values for European and Asian river systems.

PMID- 12504760
TI  - Seasonal variation in the frequency of abnormal anaphases and mitotic index
      values in wild populations of herb-Paris (Paris quadrifolia L., Trilliaceae):
      implications for genetic monitoring.
AB  - The main aim of our study was to investigate seasonal variation in the frequency
      of abnormal anaphases and mitotic index values in wild populations of herb-Paris
      (Paris quadrifolia L., Trilliaceae). Plant material was collected in the year
      2000 in Norway and in the year 2001 in Lithuania. There was statistically
      significant variation in the mitotic index values (chi(2)=1087.9, d.f.=16,
      P<0.0001) with the highest values during the active growth period in May and the
      lowest values at the end of vegetation period in September. Seasonal variation in
      the frequency of abnormal anaphases was statistically significant as well
      (chi(2)=28.23, d.f.=16, P=0.0297). The most frequent type of anaphase abnormality
      was vagrant chromosomes (64.2%) followed by bridges (28.6%), fragments (3.6%),
      sticky chromosomes (2.4%) and multipolar anaphases (1.2%). During the fieldwork,
      quite deep late frosts occurred. Mitotic index was lower in the plants collected
      immediately after the frosts or 1 week later than in the plants sampled before
      the frosts (52+/-13 and 123+/-15, respectively, P=0.0014). On the contrary,
      frequency of abnormal anaphases was statistically significantly elevated
      (P=0.0082) in plants after the frosts (6.35+/-1.54%) when compared to plants
      before the frosts (2.49+/-0.56%). Our results clearly indicated significant
      variation in the mitotic index values and frequency of abnormal anaphases in the
      wild populations of herb-Paris during the growth season. This variation may be
      related to the physiological conditions of the analysed plants as well as to
      certain ecological factors.

PMID- 12504761
TI  - Levels and behavior of 2-phenylbenzotoriazole-type mutagens in the effluent of a
      sewage treatment plant.
AB  - We previously reported on the isolation and structural determination of five 2
      phenylbenzotriazole (PBTA)-type mutagens (PBTA-1, PBTA-2, PBTA-3, PBTA-4 and PBTA
      6) in blue rayon/cotton adsorbed substances collected from surface waters at
      sites located downstream of sewage treatment plants. We also noted that PBTA-1
      and PBTA-2 were discharged from sewage treatment plants and subsequently diluted
      or decomposed while moving down the Yodo River system. However, it has not been
      investigated whether they are commonly discharged from sewage treatment plants
      into rivers. The main purpose of this study was to make a comprehensive survey of
      levels and behavior of PBTA-type mutagens in effluents discharged from the sewage
      treatment plant located along the bank of the Uji River, one tributary of the
      Yodo River system. Water samples were collected at the outlet of the sewage
      treatment plant for 16 consecutive days in May 1999 and 11 consecutive days in
      December 1999. Organic constituents were obtained via sorption to blue rayon and
      subsequent methanol elution. Extract mutagenic activity was measured using
      Salmonella typhimurium YG1024 with metabolic activation. PBTA-type mutagens (PBTA
      1, PBTA-2, PBTA-3, PBTA-4, PBTA-5 and PBTA-6) were quantified by HPLC with
      electrochemical detection, followed by HPLC purification on reverse-phase
      columns. The study showed that PBTA-2, PBTA-3, PBTA-4 and PBTA-6 were detected in
      most samples. The total contribution of these four PBTA-type mutagens to overall
      extract mutagenicity is on average 33% for the May 1999 sample and 58% for the
      December 1999 sample. The individual PBTA compounds that had the largest
      contribution to the overall mutagenicity were PBTA-3 and PBTA-4, accounting for
      11 and 16% in May 1999, and 25 and 26% in December 1999. A further comparative
      study was done in December 1999 using the blue rayon hanging method and the
      results were similar to those obtained using the blue rayon column method. In
      conclusion, the present study showed that PBTA-2, PBTA-3, PBTA-4 and PBTA-6 were
      commonly discharged from a sewage treatment plant into the Uji River, and they
      accounted for a substantial portion of the effluent mutagenicity.

PMID- 12504762
TI  - Chromosomal aberrations and sister chromatid exchanges in individuals exposed to
      arsenic through drinking water in West Bengal, India.
AB  - Arsenic contamination in groundwater has become a worldwide problem. Currently an
      unprecedented number of people in West Bengal, India and Bangladesh are exposed
      to the ubiquitous toxicant via drinking water in exposure levels far exceeding
      the maximum recommended limit laid down by WHO. This arsenic epidemic has
      devastated nine districts of West Bengal encompassing an area of 38,865 km(2)
      leading to various clinical manifestations of chronic arsenicosis. We conducted a
      human bio-monitoring study using chromosomal aberrations (CA) and sister
      chromatid exchanges (SCE) as end points to explore the cytogenetic effects of
      chronic arsenic toxicity in the population of North 24 Parganas, one of the
      arsenic affected districts in West Bengal. Study participants included 59
      individuals residing in this district where the mean level (+/-S.E.) of arsenic
      in drinking water (microg/l) was 211.70+/-15.28. As age matched controls with
      similar socio-economic status we selected 36 healthy, asymptomatic individuals
      residing in two unaffected districts--Midnapur and Howrah where the mean arsenic
      content of water (microg/l) was 6.35+/-0.45. Exposure was assessed by
      standardized questionnaires and by detecting the levels of arsenic in drinking
      water, nails, hair and urine samples. In the exposed group the mean arsenic
      concentrations in nails (microg/g), hair (microg/g) and urine (microg/l) samples
      were 9.04+/-0.78, 5.63+/-0.38 and 140.52+/-8.82, respectively, which were
      significantly high (P<0.01) compared to the corresponding control values of
      0.44+/-0.03, 0.30+/-0.02 and 5.91+/-0.49, respectively. Elevated mean values
      (P<0.01) of the percentage of aberrant cells (8.08%) and SCEs per cell (7.26)
      were also observed in the exposed individuals in comparison to controls (1.96%
      and 5.95, respectively). The enhanced rates of CAs and SCEs among the residents
      of North 24 Parganas are indicative of the cytogenetic damage due to long term
      exposure to arsenic through consumption of contaminated water.

PMID- 12504763
TI  - Effect of dithiocarbamate pesticide zineb and its commercial formulation,
      azzurro. IV. DNA damage and repair kinetics assessed by single cell gel
      electrophoresis (SCGE) assay on Chinese hamster ovary (CHO) cells.
AB  - Single cell gel electrophoresis (SCGE) was used to analyse dithiocarbamate zineb-
      and the zineb-containing technical formulation azzurro-induced DNA damage and
      repair in CHO cells. Cells were treated with zineb (50.0 microg/ml) or azzurro
      (100.0 microg/ml) for 80min, washed and reincubated in pesticide-free medium for
      0-12h until SCGE. Viability of treated cells (0 h) did not differ from control
      remaining unchanged up to 6h of incubation. After 12h, viability decreased up to
      70 and 54% in zineb- and azzurro-treated cultures, respectively. SCGE revealed at
      0 h the absence of undamaged cells and an increase of slightly damaged and
      damaged cells in zineb-treated cultures or by an increase in damaged cells in
      azzurro-treated cultures. For both chemicals, a time-dependent repair of
      pesticide-induced DNA damage within a 0-12h post-treatment incubation period was
      observed. Overall, damaged cells decreased as a function of the repair time for
      both pesticides while the slightly damaged cells decreased as a function of the
      repair time of zineb-induced DNA damage. Concomitantly, a time-dependent increase
      of undamaged cells was observed within the 0.5-12h repair time for both
      pesticides. At 12h after treatment, no differences in the frequencies of
      undamaged, slightly damaged and damaged cells were found between both zineb- or
      azzurro-treated cultures and control values as well as between zineb- and azzurro
      treated cells. Immediately after exposure, nuclear DNA from zineb and azzurro
      treated cells were larger and wider than nuclear DNA from untreated cells. When
      damaged cells were allowed to repair, a time-dependent decrease of the amount of
      free DNA migrating fragments was observed committed only to damaged cells but not
      in slightly or undamaged cells. On the other hand, no time-dependent alteration
      on nuclear DNA width within the 0-12h repair period was observed.

PMID- 12504764
TI  - The associations among semen quality, oxidative DNA damage in human spermatozoa
      and concentrations of cadmium, lead and selenium in seminal plasma.
AB  - To explore the associations among semen quality, oxidative DNA damage in human
      spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma,
      56 non-smoking subjects were asked to collect semen by masturbation into a
      sterile wide-mouth metal-free plastic container after 3 days of abstinence. The
      conventional semen parameters were analysed. The concentrations of Cd, Pb and Se
      in seminal plasma were detected using atomic absorption spectrophotometer. 8-OHdG
      levels in sperm DNA were measured using HPLC-EC. The results showed that the
      geometric mean concentrations of Cd, Pb and Se were 0.78, 7.8 and 51.4 microg/l,
      respectively. The geometric mean of 8-OHdG/10(6) dG was 51.4 (95% CI: 21.5
      123.0). A significant inverse correlation exists between Cd and sperm density (r=
      0.28, P<0.05), and between Cd and sperm number per ejaculum (r=-0.27, P<0.05). In
      contrast, there was a significantly positive correlation between Se and sperm
      density (r=0.50, P<0.01), between Se and sperm number (r=0.49, P<0.01), between
      Se and sperm motility (r=0.40, P<0.01), and between Se and sperm viability
      (r=0.38, P<0.01). No statistically significant correlation was observed between
      Pb and semen quality. A significant inverse correlation was observed between 8
      OHdG and sperm density (r=-0.34, P<0.01), between 8-OHdG and sperm number per
      ejaculum (r=-0.30, P<0.01), and 8-OHdG and sperm viability (r=-0.24, P<0.05). 8
      OHdG was significantly correlated with Cd in seminal plasma (r=0.55, P<0.01). A
      significant but weak positive correlation was found between 8-OHdG and Pb
      concentration in seminal plasma (r=0.28, P<0.05). In contract, a significant
      inverse correlation was observed between 8-OHdG and Se concentration in seminal
      plasma (r=-0.40, P<0.01). The results indicate that Cd in seminal plasma could
      affect semen quality and oxidative DNA damage in human spermatozoa. Se could
      protect against oxidative DNA damage in human sperm cells. Pb did not appear to
      have any association with the semen quality when concentration of Pb in seminal
      plasma was below 10 microg/l.

PMID- 12504765
TI  - Anesthesia of fish with benzocaine does not interfere with comet assay results.
AB  - Fish blood erythrocytes are frequently used as sentinels in biomonitoring
      studies. Usually, fish blood is collected by painful cardiac or caudal vein
      punctures. Previous anesthesia could decrease animal suffering but it is not
      known at present whether anesthesia can cause confounding effects. Therefore,
      using the alkaline single cell gel (SCG)/comet assay with blood erythrocytes of
      the cichlid fish Nile tilapia, we tested for a possible modulation of induced DNA
      damage (methyl methanesulfonate; MMS) by the anesthetic benzocaine administered
      by bath exposure (80mg/l for approximately 10min). Furthermore, benzocaine (80
      600mg/l) was tested for its genotoxic potential on fish erythrocytes in vitro and
      for potential interactions with two known genotoxins (MMS and hydrogen peroxide).
      Our results did neither indicate a significant increase in the amount of DNA
      damage (even after a 48h follow-up), nor indicated interactions with MMS-induced
      DNA damage when fish were exposed to benzocaine in vivo. There was also no
      increase in DNA damage after in vitro exposure of fish erythrocytes to
      benzocaine. Clear concentration-related effects were observed for the two
      genotoxins in vitro, which were not significantly altered by the presence of
      benzocaine. These results suggest that anesthesia of fish does not confound comet
      assay results and the use of blood samples from anesthetized fish can be
      recommended with regard to animal welfare.

PMID- 12504766
TI  - Spontaneous tandem-base mutations (TBM) show dramatic tissue, age, pattern and
      spectrum specificity.
AB  - To supplement a previous analysis of spontaneous tandem-base mutations (TBM) in
      the lacI gene of Big Blue((R)) mice, 2658 additional mutants were sequenced from
      13 tissues and 44 spontaneous TBM were identified (tripling the sample size).
      Previous findings were confirmed and generalized and several new observations
      were made. TBM differ from single and other double mutations in that TBM
      frequency varies dramatically with tissue type. In certain tissues, most notably
      male germ cells, no TBM are observed despite screening as many as 26 million
      plaque forming units. TBM are most frequent in kidney and liver (3.45 and 2x10(
      6), respectively), accounting for 7.6 and 4.8% of all mutational events in kidney
      and liver, respectively. There is a trend for elevated TBM frequency in thymic
      lymphomas in p53-deficient mice. TBM are more frequent in old age in both liver
      and kidney. TBM differ from single mutations and other double mutations because
      they display a marked difference in pattern and dramatic tissue specificity for
      target sequence. Five of the 78 possible TBM outcomes comprise 79% of those
      observed, and mutations at GG/CC predominate. TBM in mice were compared with TBM
      found in human mutation databases. TBM are also rare in the human germline (one
      in 5133 germline mutations reported in five human mutation databases). In
      general, the types of somatic TBM are similar in mice and humans except for an
      excess of TG/CA to CA/TG TBM in humans (TBM related to ultraviolet light-induced
      skin cancer were excluded). TBM may be the result of unknown mechanisms that may
      have some similarities in mice and humans.

PMID- 12504767
TI  - Inhibition by (+/-)-indenestrol A of interferon gamma-stimulated nitric oxide
      formation in murine macrophage RAW 264.7 cells.
AB  - We examined the effects of (+/-)-indenestrol A (IA), an antioxidative and
      superoxide-producing metabolite of diethylstilbestrol (DES), on the activation of
      murine macrophages (RAW 264.7 cells) in vitro, particularly with regard to
      interferon (IFN)-gamma-induced nitric oxide (NO) production. (+/-)-IA inhibited
      NO production more strongly than DES as assessed by a nitrite assay. The
      inhibitory effect of (+/-)-IA on IFN-gamma-induced intracellular NO production
      was confirmed by direct staining of intracellular NO with diaminofluorescein-2
      diacetyl. Inhibition of NO production was confirmed by Western blot analysis of
      IFN-gamma-induced NO synthase. Under IFN-gamma-stimulated conditions, the IFN
      gamma activation site (GAS), which was the most important transcription factor,
      was significantly inhibited by (+/-)-IA. (+/-)-IA also promoted the activation of
      NF-kappaB. (+/-)-IA at 1 and 3 microM delayed the onset of apoptosis. Our results
      suggest that (+/-)-IA inhibited the activation of macrophages, resulting in the
      suppression of NO-mediated apoptosis. These results suggest a novel mechanism for
      the carcinogenic promoting activity of DES via its metabolite, (+/-)-IA.

PMID- 12504768
TI  - Valproic acid and lamotrigine treatment during pregnancy. The risk of chromosomal
      abnormality.
AB  - A baby born to an epileptic mother had dysmorphological features associated with
      47,XXX karyotype. The mother had been treated with valproic acid (1800mg per day)
      and lamotrigine (100mg per day) throughout pregnancy. Dysmorphological features
      detected in baby were intrauterine growth retardation, hypertelorism, flattened
      nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped
      mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum
      atrial septal defect, bilateral hammer toes and decreased creases on the soles.
      At 6 months old she showed motor retardation. The molecular analysis of parents
      revealed that extra X chromosome was inherited from the mother. In this case
      whether the dysmorphological features and 47,XXX karyotype were caused by
      lamotrigine and valproic acid treatment during pregnancy or coincidence is in
      question.

PMID- 12504769
TI  - The effect of treating Drosophila females with chlorophyllin on the yield of
      dominant lethals recovered from irradiated sperm.
AB  - Evidence is presented that treating the Drosophila female with chlorophyllin
      (CHLN) has a marked effect on the yield of dominant lethals induced by the
      irradiation of sperm. The yield is significantly greater in the embryonic period
      (between the egg and the first instar) and is significantly reduced in
      postembryonic stages compared with a sucrose control.

PMID- 12504770
TI  - [Comparison with dose-volume histograms of two conformal irradiation techniques
      used for the treatment of T2N0M0 nasopharyngeal cancer, one with association of
      photons and protons and another with photons alone].
AB  - Purpose- There is a relationship between the local control rate of the
      nasopharyngeal cancer and the total dose delivered within the tumoral volume. In
      contrast, the relation between the dose and the irradiated volume and the risk of
      complication is not clearly defined. That is why, in patients presenting with a
      locally advanced nasopharyngeal cancer, we compared the dose-volume distribution
      of irradiated tissues, obtained from two 3D conformal irradiation techniques.
      Patients and methods- Between January 2000 and June 2001, 5 patients, 3 males and
      2 females, with a median age of 32 years and presenting with a T4N0M0
      nasopharyngeal cancer received a chemoradiotherapy. Radiotherapy combined photons
      and protons beams and the platin-based chemotherapy was delivered in three
      intravenous injections at d1, 22, 43 of the irradiation. To calculate the
      dosimetry, a CT scan and a MRI were performed in all the patients. The gross
      tumor volume (GTV) was delineated from the imagery, three clinical tumor volumes
      were defined, the CTV1 was the GTV and the whole nasopharynx, the CTV2 was the
      CTV plus a 10 mm-margin and the CTV3 was the CTV2 and the nodes areas (cervical
      and subclavicular). Prophylactic dose within node areas was 44 Gy. Prescribed
      doses within CTV2 and GTV or CTV1 were 54 Gy/CGE (Cobalt Gy Equivalent, for an
      EBR = 1,1) and 70 Gy/CGE, respectively. Irradiation was delivered with fractions
      of 1.8 or 2.0 Gy/CGE, with 44 Gy or 54 Gy by photons and with 16 or 26 CGE by
      protons. According to dose-volume histograms obtained from the dosimetry planning
      by protons and photons and from the theoretical dosimetry by photons lonely, for
      the different volumes of interest, GTV, CTV2, and organs at risk (optic nerves,
      chiasm, internal ears, brainstem, temporal lobes), we compared the averages of
      the maximum, minimum and mean doses and the averages of the volumes of organs of
      interest encompassed by different isodoses.Results- Calculated averages of
      minimum, maximum and mean doses delivered within GTV were superior for the
      treatment with combined photons and protons than with photons alone. The average
      GTV encompassed by the 70 Gy/CGE isodose was larger by 65% with the association
      compared to photons alone. The conformation ratio (tissue volume encompassed by
      the 95% isodose/GTV encompassed by the 95% isodose) was 3.1 with the association
      compared to 5.7 with photons alone. For the CTV2, there were no differences in
      different criteria according to the both irradiation techniques. For the
      critical, radiosensitive organs, the comparison of the majority of the criteria
      was in favour of the association of protons and photons. Overall, 78% of the
      criteria were in favour of the association.Conclusion- For locally advanced
      nasopharyngeal cancer without clinical adenopathy, irradiation by photons and
      protons increases the tumor volume irradiated at the prescribed dose and
      decreases the volume or critical organs irradiated and the total dose delivered
      within them.

PMID- 12504771
TI  - Male breast cancer. A report of 71 cases.
AB  - Male breast cancer is rare; it constitutes 0.2-1.5% of all malignant tumours in
      men and 1% of all breast cancers. The goal of this retrospective study is to
      analyse the epidemiologic, clinic, therapeutic and evolutive profiles of this
      disease in 71 cases collected at the National Institute of Oncology in Rabat,
      Morocco, between the years 1985 and 1998. The median age was 60 years. No
      significant risk factor was found. The average consultation's delay was 35
      months. The main clinical complaint was a mass beneath the areola in 86% of the
      cases, associated with ulceration in 18% of the cases. For that, the disease was
      diagnosed at an advanced stage. Infiltrating ductal carcinoma was the most
      frequent pathologic type (91.5% of cases). Management consisted especially of
      radical mastectomy, followed by adjuvant radiotherapy and hormonal therapy with
      or without chemotherapy. It was possible to follow 58 of the patients. The median
      of follow-up was 30 months. The evolution has been characterized by local
      recurrence, after a median delay of 36 months, in five cases (8.5% of all
      patients). Metastasis occurred, after a median delay of 12 months, in 14 cases
      (24% of all patients). The site of metastasis was the bone in six cases, lung in
      five cases, liver in one case, liver and skin in one case and pleura and skin in
      one case. There were three cases of death. In one case, death was related to lung
      metastases. In the two remaining cases, death was due to comorbid disease.
      Progression was observed in one case.

PMID- 12504772
TI  - Fetal dose during radiotherapy: clinical implementation and review of the
      literature.
AB  - Two pregnant patients received radiation therapy, one for the treatment of
      mediastinal Hodgkin's lymphoma and the other for a head and neck squamous cell
      carcinoma. The fetuses were both protected by additional shielding which reduced
      the unshielded exposure of the first fetus by 20-40%, and that of the second by
      20-60%. The first child received an estimated maximum dose of 42 cGy, the second
      a maximum dose of 9 cGy. Treatment details are reported and a review of the
      literature that addresses the possible irradiation-induced side effects at low
      doses is included.

PMID- 12504773
TI  - [Primary adenocarcinoma of the male urethra. A case report].
AB  - Primary adenocarcinoma of the male urethra is very uncommon, accounts for 5% of
      primary urethral cancers. All types of urethral carcinomas account for less than
      1% of urinary malignancies in man. The prognosis remains poor despite the wide
      surgical treatment. The place of chemotherapy combined with radiotherapy must be
      defined by other studies. We report a case of primary locally advanced
      adenocarcinoma arising in the bulbo-membranous urethra. The patient was 29 years
      old, without any previous history of venerian disease. He was treated by combined
      external beam radiotherapy (total dose 67Gy) and chemotherapy (Cisplatinum). A
      marked reduction of tumor volume has been noted but the patient died because of
      the appearance of bone metastasis which failed to the systemic therapy.

PMID- 12504774
TI  - [Sarcoma botryoide of the uterine cervix: report of a case].
AB  - Botryoide sarcoma of the uterine cervix is a very rare tumor of the young woman
      or during genial activity. Less than 100 cases have been reported in the
      literature. The treatment ranged from radical surgery to conservative surgery
      followed by chemotherapy. We report a case of cervical botryoide rhabdomyosarcoma
      occurred in a 33 year-old woman treated primary by chemotherapy followed by
      surgery and adjuvant chemotherapy. The patient died by extensive metastatic
      retroperitoneal nodes and lung.

PMID- 12504775
TI  - [Primary squamous cell carcinoma of the breast. Report of three cases].
AB  - Primary squamous cell carcinoma of the breast is a rare neoplasma included in
      metaplastic breast cancer. The histogenesis remains unknown. Clinical and
      radiological appearances are not specific. Nodal involvement is rare and hormones
      receptors are negative. The treatment is based on surgery associated to radiation
      therapy and chemotherapy. Prognosis seems to be similar to others breast
      carcinoma. We report three cases of primary squamous cell carcinoma of the breast
      recruited at National Institute of Oncology with review of the literature.

PMID- 12504776
TI  - [The French project ETOILE: review of clinical data for light ion hadrontherapy].
AB  - The Lawrence Berkeley Laboratory was the pioneer in light ions hadrontherapy with
      almost 2500 patients treated between 1957 and 1993 with Helium and Neon. The NIRS
      (National Institute For Radiological Science, Chiba, Japan) was the first
      dedicated medical centre for cancer with more than 1200 patients exclusively
      treated with carbon ion from 1994. A three-year 70 to 100% local control was
      reported for radio-resistant cancers, supporting the use of high LET particles.
      Hypo-fractionation was particularly explored for lung cancers and hepatocarcinoma
      (4 sessions only). Dose escalation studies demonstrated a tumour dose-effect and
      permitted to precise dose constraints for healthy tissues especially for the
      rectum. More than 140 patients were treated with carbon ion exclusively or
      associated with photons since 1997 in the GSI laboratory Gesellschaft Fur
      Schwerionenforschung, Darmstadt, Germany). A very high local control was also
      obtained for radioresistant cancer of the base of the skull. Preliminary clinical
      data seem to confirm the expected therapeutic gain with light ions, due to their
      ballistic and radio-biological properties, and justify the European projects for
      the construction of dedicated medical facilities for cancers. The French "Etoile"
      project will be integrated in the European hadrontherapy network "Enlight", with
      the objectives to coordinate technologic, medical and economic features.

PMID- 12504778
TI  - Propentofylline protects beta-amyloid protein-induced apoptosis in cultured rat
      hippocampal neurons.
AB  - beta-Amyloid protein 1-42 (beta42) can induce apoptosis in the cultured
      hippocampal neurons, suggesting that it plays an important role in causing
      neurodegeneration in Alzheimer's disease. Recently, propentofylline, a synthetic
      xanthine derivative, has been reported to depress ischemic degeneration of
      hippocampal neurons in gerbils. The present study investigated whether or not
      propentofylline affected the beta42-induced apoptosis of hippocampal neurons, and
      if so, which type of signaling machinery works in the neuroprotective action of
      propentofylline. Addition of propentofylline markedly attenuated the beta42
      induced cell death of rat hippocampal neurons. The amyloid protein certainly
      induced apoptosis in the cultured hippocampal cells revealed by nuclear
      condensation, caspase-3 activation and an increase of Bax. Intriguingly,
      propentofylline blocked both the apoptotic features induced by beta42 and further
      induced an anti-apoptotic protein, Bcl-2, during a short time of incubation. The
      neuroprotective action of propentofylline was comparably replaced with dibutyryl
      cAMP (dbcAMP) and was completely suppressed by a low concentration of specific
      protein kinase A (PKA) inhibitor. Taken altogether, the data strongly suggest
      that the protection of propentofylline on the beta42-induced neurotoxicity is
      caused by enhancing anti-apoptotic action through cAMP-PKA system.
      Propentofylline as a therapeutic agent to Alzheimer's disease is discussed.

PMID- 12504779
TI  - GEA3162 stimulates Ca2+ entry in neutrophils.
AB  - We showed that 5-amino-3-(3,4-dichlorophenyl)1,2,3,4-oxatriazolium (GEA3162), a
      lipophilic nitric oxide (NO)-releasing agent, induced Ca(2+) entry into rat
      neutrophils in a concentration-dependent manner, whereas the guanylyl cyclase
      inhibitors, 6-anilino-5,8-quinolinequinone (LY83583) and 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ), had no effect on GEA3162-induced response. The GEA3162
      induced Ca(2+) entry was not observed in a Ca(2+)-free medium. GEA3162 did not
      potentiate but reduced the store-emptying activated Ca(2+) entry caused by
      cyclopiazonic acid. Stimulation of cells with GEA3162 in the absence of
      extracellular Ca(2+) followed by addition of cations showed that only Ca(2+) but
      not Ba(2+) and Sr(2+) entry occurs. Store-operated Ca(2+) entry was sensitive to
      La(3+) and Ni(2+) inhibition, whereas the GEA3162-induced Ca(2+) entry was
      sensitive to La(3+) but resistant to Ni(2+). cis-N-(2
      Phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12,330A) and calyculin A
      diminished the Ca(2+) entry activated by cyclopiazonic acid as well as by
      GEA3162. In contrast, 2-aminoethyldiphenyl borate (2-APB) diminished
      cyclopiazonic acid-but enhanced GEA3162-induced [Ca(2+)](i) change. Genistein
      effectively attenuated the cyclopiazonic acid-but slightly inhibited GEA3162
      induced [Ca(2+)](i) change. Application of neomycin and high extracellular Ca(2+)
      concentration did not induce [Ca(2+)](i) rise. These data suggest that GEA3162
      induced Ca(2+) entry and regulated Ca(2+) signal, through direct protein thiol
      oxidation. The action of GEA3162 demonstrates characteristics that distinguish it
      from the store-operated mechanism in neutrophils and therefore is likely to
      represent an entirely distinct pathway. Extracellular Ca(2+)-sensing receptor is
      not existing in neutrophils.

PMID- 12504780
TI  - Antagonist effect of pseudohypericin at CRF1 receptors.
AB  - St. John's wort (Hypericum perforatum L.) is widely used for the treatment of
      mild to moderately severe depression. However, the nature of its active
      principles and the exact mode of antidepressant action are still unknown. It has
      been suggested repeatedly in preclinical and clinical studies that the content of
      the acylphloroglucinol hyperforin decisively contributes to the antidepressant
      efficacy of St. John's wort extracts. Experimental studies in vivo also indicate
      that the naphthodianthrone hypericin may reduce the activity of the hypothalamic
      pituitary-adrenal axis. Exacerbated hypothalamic-pituitary-adrenal activity has
      often been associated with depressive states in patients. Corticotropin-releasing
      factor (CRF) seems to be a major determinant in the regulation of the
      hypothalamic-pituitary-adrenal activity via activation of CRF(1) receptors. In
      the present study, we investigated the CRF(1) receptor antagonist activity of
      three main constituents of St. John's wort (hypericin, pseudohypericin and
      hyperforin) by measuring their effect on CRF-stimulated cAMP formation in
      recombinant Chinese hamster ovary (CHO) cells. As a selectivity test, the
      compounds were also tested against calcitonin in the same cells. Of the three
      compounds tested, only pseudohypericin selectively antagonised CRF (K(B) 0.76
      microM). Hypericin and hyperforin affected both CRF and calcitonin with similar
      potencies and the same type of behaviour (competitive antagonism for hypericin,
      noncompetitive for hyperforin). It is concluded that pseudohypericin is the only
      real CRF(1) receptor antagonist of the three constituents tested. In addition,
      evidence is provided that beside hyperforin, both pseudohypericin and hypericin
      are implicated in the antidepressant efficacy of St. John's wort.

PMID- 12504781
TI  - In vitro effect of sanguinarine alkaloid on binding of [3H]candesartan to the
      human angiotensin AT1 receptor.
AB  - The type of interaction of 5-methyl-2,3,7,8
      bis(methylenedioxy)benzo[c]phenanthridinium (sanguinarine), an alkaloid isolated
      from the root of Bocconia frutescens L., with the human angiotensin AT(1)
      receptor was evaluated in both intact cells and membrane binding of [3H](2-ethoxy
      1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic
      acid) ([3H]candesartan). The results indicate that the inhibition of
      [3H]candesartan binding by sanguinarine is independent of cell viability, since
      the alkaloid inhibited at a similar extent radioligand binding on both intact
      Chinese hamster ovary (CHO) cells transfected with the human angiotensin AT(1)
      receptor (hAT(1)) and their cell membranes (K(i)=0.14 and 1.10 microM,
      respectively). The unsuccessful recovery of [3H]candesartan binding after washing
      sanguinarine off the cells suggested a nearly irreversible or slow reversible
      interaction. Saturation binding studies showed a substantial reduction of the
      B(max) without affecting the K(d). In addition, the presence of 2-n-butyl-4chloro
      5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole
      (losartan) could not prevent sanguinarine inhibition of [3H]candesartan binding
      neither. The present findings indicate that sanguinarine interacts with the
      receptor in a slow, nearly irreversible and noncompetitive manner.

PMID- 12504782
TI  - Assessment of mazindane, a pro-drug form of mazindol, in assays used to define
      cocaine treatment agents.
AB  - The current studies compared mazindane (5-(4-chlorophenyl)-2,3-dihydro-5H-imidazo
      [2,1a] isoindole) hydrogen sulfate, a water soluble pro-drug of mazindol (5-(4
      chlorophenyl-2,3-dihydro-5H-imidazo [2,1-a] isoindol-5-ol), with mazindol in
      assays used to define cocaine treatment agents. Both compounds enhanced motor
      activity (LMA) in Swiss Webster mice with ED(50) values of 2.5 mg/kg i.p. for
      mazindane and 3.9 mg/kg i.p. for mazindol. At 25 mg/kg mazindane displayed toxic
      effects and death while mazindol was effect/death free at 50 mg/kg. In Sprague
      Dawley rats trained to discriminate cocaine from saline both compounds fully
      substituted for cocaine with mazindane being fourfold more potent in the total
      session (0.33 vs. 1.3 mg/kg i.p.) and first reinforcer (0.29 vs. 1.2 mg/kg i.p).
      Complete substitution was observed in rhesus monkeys trained to discriminate
      cocaine from saline with ED(50) values for mazindane (0.134 mg/kg i.m.) and
      mazindol (0.119 mg/kg i.m.). Mazindol exhibited little or no activity at 10(-5) M
      in inhibiting radioligand binding at 14 neurotransmitter sites while mazindane
      gave weak activity at the histamine H(1) and 5-hydroxytryptamine 5-HT(3) sites.
      These results demonstrate that mazindane could be a useful alternative to
      mazindol as a pharmacological tool because of its similar profile of activity and
      enhanced water solubility.

PMID- 12504783
TI  - A comparison of the antinociceptive effects of voltage-activated Na+ channel
      blockers in two rat models of neuropathic pain.
AB  - The pain-relieving effects of various voltage-activated Na(+) channel blockers
      have been evaluated in two rat models of neuropathic pain; the photochemically
      induced nerve injury model (Gazelius) and spared nerve injury model. Lidocaine
      (up to 40 mg/kg, i.p.) and lamotrigine (up to 60 mg/kg, i.p.) had no effect on
      mechanical or cold allodynia in either model. However, lamotrigine (10, 30 and 60
      mg/kg) significantly attenuated mechanical hyperalgesia in the spared nerve
      injury model, while mexiletine (25 and 37.5 mg/kg, i.p.) attenuated mechanical
      allodynia in the Gazelius model. Tocainide (50, 75 and 100 mg/kg, i.p.)
      significantly reduced all types of pain behaviour measured. The present results
      show that these voltage-activated Na(+) channel blockers have broadly similar
      antinociceptive effects in these two models of neuropathic pain. They also show
      that these drugs can have markedly different effects on distinct neuropathic pain
      related behaviours within models.

PMID- 12504784
TI  - Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular
      endothelial growth factor expression and vascular leakage in a streptozotocin
      induced diabetic rat model.
AB  - Overexpression of vascular endothelial growth factor (VEGF) is implicated in the
      development of vascular leakage and retinal neovascularization in diabetic
      subjects. The objective of this study was to determine whether celecoxib, a
      selective cyclooxygenase-2 enzyme inhibitor, reaches ocular tissues following
      oral administration and inhibits the retinal VEGF expression and vascular leakage
      in a streptozotocin-induced diabetic rat model. After administering a single
      intraperitoneal injection of streptozotocin (60 mg/kg) to Sprague-Dawley rats and
      ensuring the induction of diabetes at the end of 24 h, celecoxib was administered
      b.i.d. by oral gavage (50 mg/kg). On day 8, the animals were sacrificed and the
      retinal VEGF and cyclooxygenase-2 mRNA levels, ocular tissue celecoxib
      concentrations, and the vitreous/plasma protein ratio were determined. In
      diabetic rats, the retinal VEGF mRNA expression was 2.3-fold compared to
      controls, with a corresponding increase in cyclooxygenase-2 mRNA expression.
      Celecoxib treatment inhibited VEGF mRNA expression without any significant
      reduction in cyclooxygenase-2 mRNA. Furthermore, the retinal vascular leakage
      estimated as vitreous to plasma protein ratio increased in diabetic animals from
      0.35+/-0.1 to 1.1+/-0.1 and celecoxib treatment significantly decreased this
      ratio to 0.4+/-0.1. Celecoxib levels were 24.8+/-6.6, 1.9+/-1, 1.7+/-0.8, and
      6.9+/-0.9 ng/mg in the retina, vitreous, lens, and cornea, respectively. The
      plasma celecoxib levels were 85+/-24 ng/ml. Thus, celecoxib reaches the retina
      after oral administration and reduces diabetes-induced retinal VEGF mRNA
      expression and vascular leakage by inhibiting the activity of cyclooxygenase-2
      enzyme.

PMID- 12504785
TI  - Evaluation of endomorphin-1 on the activity of Na(+),K(+)-ATPase using in vitro
      and in vivo studies.
AB  - The goal of this study was to investigate the effects of endomorphin-1 on
      Na(+),K(+)-ATPase activity in mouse brain synaptosome in vitro, and its
      antinociceptive interaction with the Na(+),K(+)-ATPase inhibitor ouabain.
      Endomorphin-1 (0.1 nM-10 microM) produced a concentration-dependent (EC(50):
      43.19 nM, CI: 23.38-65.71 nM, E(max): 25.86%, CI: 24.53-27.20%), naloxone
      reversible increase of the synaptosomal Na(+),K(+)-ATPase activity. The
      intrathecally (i.t.) administered endomorphin-1 (2-20 microg) produced a dose
      dependent short-lasting increase in the tail-flick latency. Ouabain itself (1
      1000 ng, i.t.) did not cause antinociception. Treatment with 10 ng ouabain
      significantly decreased the antinociceptive effect of 2 microg endomorphin-1, but
      none of the other combinations did significantly differ from the endomorhin-1
      treated groups. These data indicate that endomorphin-1 increases the activity of
      Na(+),K(+)-ATPase in vitro but this effect may play a weak role in the
      antinociception induced by intrathecal endomorphin-1.

PMID- 12504786
TI  - Attenuated arterial and venous constriction in conscious rats with streptozotocin
      induced diabetes.
AB  - We examined if arterial or venous constriction is impaired in early diabetes.
      Dose-pressor and mean circulatory filling pressure (index of venous tone)
      response curves to noradrenaline and angiotensin II were constructed in four
      groups of conscious, instrumented, Wistar rats pretreated with streptozotocin (60
      mg/kg i.v.) or vehicle at 2 weeks prior to the study. Rats with diabetes,
      relative to controls, had increased ED(50) (reduced potency) for the pressor (2.5
      fold of control) and mean circulatory filling pressure (4.3-fold of control)
      response to noradrenaline, as well as reduced maximum pressor response (efficacy)
      to noradrenaline (diabetic, 74+/-8 mm Hg; control, 96+/-5 mm Hg). Diabetic rats
      also had reduced potency (ED(50), 5-fold of control) of the pressor response to
      angiotensin II; however, maximum pressor response and dose-mean circulatory
      filling pressure curve to angiotensin II were similar in both groups. Therefore,
      arterial and venous constrictions are impaired at an early phase of type I
      diabetes.

PMID- 12504787
TI  - The stable pyrimidines UDPbetaS and UTPgammaS discriminate between contractile
      cerebrovascular P2 receptors.
AB  - Extracellular nucleotides were used to characterise the contractile P2 receptors
      in the rat basilar artery. The isometric tension was recorded in vitro and
      receptor mRNA expression was examined by reverse transcriptase polymerase chain
      reaction (RT-PCR) after endothelium-denudation. Transient vasoconstriction was
      evoked by alphabeta-methylene-adenosine triphosphate (alphabeta-MeATP),
      indicating the presence of P2X(1) receptors. The P2Y receptors were analysed
      after P2X receptor desensitisation with 10 microM alphabeta-MeATP. Uridine
      diphosphate (UDP) and uridine triphosphate (UTP) induced sustained contractions
      of similar magnitude. The stable nucleotide analogue, uridine 5'-O
      thiodiphosphate (UDPbetaS), was clearly more potent than uridine 5'-O-3
      thiotriphosphate (UTPgammaS), suggesting prominent contractile effects of P2Y(6)
      receptors. P2Y(2) and P2Y(4) receptors might also be involved in nucleotide
      responses, since UTPgammaS and adenosine 5'-O-3-thiotriphosphate (ATPgammaS) were
      of similar potency. The P2Y(1) selective agonists, adenosine 5'-O-thiodiphosphate
      (ADPbetaS) and 2-methylthioadenosine diphosphate (2-MeSADP) did not induce
      contractions. RT-PCR analysis demonstrated P2X(1), P2Y(1), P2Y(2) and P2Y(6)
      receptor mRNA expression, while the P2Y(4) band was weak. In conclusion,
      extracellular nucleotides induce contractions of cerebral arteries primarily by
      activation of P2Y(6) receptors on smooth muscle cells, with a lesser contribution
      of P2Y(2) and P2X(1) receptors. Although mRNA for the P2Y(1) receptor was
      detected by RT-PCR, it does not mediate contraction.

PMID- 12504788
TI  - Role of voltage-gated cation channels and axon reflexes in the release of sensory
      neuropeptides by capsaicin from isolated rat trachea.
AB  - In order to reveal the role of axon reflexes and sensory receptors in sensory
      neuropeptide release in response to capsaicin, liberation of substance P,
      calcitonin gene-related peptide and somatostatin from isolated rat tracheae was
      investigated in the presence of voltage-sensitive Na(+) and Ca(2+) channel
      blocking agents. Neuropeptide release induced by capsaicin (10 nM) remained
      unchanged in the presence of 25 mM lidocaine, 1 microM tetrodotoxin or the N-type
      Ca(2+) channel inhibitor, omega-conotoxin GVIA (100-300 nM). Peptide release by
      100 pulses of 2 Hz field stimulation was prevented by lidocaine or tetrodotoxin.
      Omega-agatoxin TK (250 nM) significantly inhibited and Cd(2+) (200 microM)
      prevented capsaicin-induced neuropeptide release. These results suggest that
      chemical stimulation-induced neuropeptide release does not involve activation of
      fast Na(+) channels or N- and P-type voltage-dependent Ca(2+) channels, but
      contribution of Q-type Ca(2+) channels is possible. Sensory neuropeptides are
      released by capsaicin from sensory receptors without axon reflexes.

PMID- 12504789
TI  - Characterisation of bradykinin B1 and B2 receptors using rat isolated vas
      deferens.
AB  - The actions of bradykinin and its metabolite des-Arg(9) bradykinin are mediated
      through activation of bradykinin B(2) and B(1) receptors, respectively. The aim
      of the present study was to characterize native bradykinin receptors focusing on
      induction and desensitization using rat isolated vas deferens. Tissues were
      mounted in organ baths for isometric recordings and neurogenically mediated
      contractions were evoked by electrical stimulation. Des-Arg(9) bradykinin
      enhanced the magnitude of the electrically evoked contractions and this effect
      (which was sensitive to blockade by the peptide bradykinin B(1) receptor
      selective antagonist B9858, Lys-Lys-(Hyp(3),Cpg(5),D-Tic(7),Cpg(8))des-Arg(9)
      bradykinin) was only observed following a pre-incubation period and was greatest
      following 5 h of pre-incubation. Bradykinin also potentiated neurogenically
      evoked contractions and this effect was sensitive to blockade by Hoe 140 (D
      Arg(Hyp(3),Thi(5),D-Tic(7),Oic(8))bradykinin, a peptide bradykinin B(2) receptor
      antagonist) and was present without pre-incubation but was increased by pre
      incubation and reached maximum at the 5-h incubation time point. Responses to
      bradykinin were larger than those to des-Arg(9) bradykinin. Bradykinin responses
      did not show desensitization on repeated agonist stimulation. These data confirm
      in rat isolated vas deferens bradykinin B(2), but not B(1), receptors are
      constitutively expressed, that both receptor populations are inducible and B(2)
      receptors do not exhibit desensitization.

PMID- 12504790
TI  - Beneficial effect of pharmacological mobilization of bone marrow in experimental
      cerebral ischemia.
AB  - Bone marrow stem cells are able to differentiate into nervous and endothelial
      cells. In our study, we found that administration of a bone marrow-stimulating
      factor (granulocyte colony-stimulating factor; G-CSF 50 microg/kg) decrease the
      brain infarct volume and enhance survival rate in a model of cerebral ischemia.
      Taken together, these data suggest a beneficial effect of a pharmacological
      endogenous bone marrow mobilization in the course of cerebral ischemia and open a
      new direction for cellular therapy strategy in stroke.

PMID- 12504791
TI  - Advances in the pathophysiology of constitutive and inducible cyclooxygenases:
      two enzymes in the spotlight.
AB  - The aim of this commentary is to discuss recent data on the role of
      prostaglandins generated by both constitutive and inducible cyclooxygenases
      (COXs). According to a popular hypothesis, COX-1 generates 'good' prostaglandins
      for physiological 'housekeeping' functions like gastrointestinal (GI) mucosal
      integrity and regulation of renal blood flow, while COX-2 forms the 'bad'
      prostaglandins responsible for inflammatory symptoms. However, recent data show
      that the biological functions of prostanoids formed by the two enzymes are much
      more complex and interrelated than previously appreciated. Experimental evidence
      indicates that a full inflammatory response is likely sustained by prostanoids
      generated by both enzymes, and an effective anti-inflammatory effect requires the
      inhibition of the two enzymes. Similarly, the selective inhibition of either COX
      1 or COX-2 does not elicit GI damage, but inhibition of both enzymes is necessary
      for GI mucosal damage to develop. Prostaglandins generated by both enzymes
      contribute to normal renal function by regulating the vascular tone and the
      normal blood flow. The synthesis of endothelial prostacyclin is mainly driven by
      COX-2, so that the selective COX-2 inhibition may bias vascular prostaglandin
      synthesis in favour of COX-1-derived thromboxane A(2) in platelets, leading to a
      prothrombotic outcome. Moreover, prostaglandins formed by COX-2 appear to have a
      major role in myocardial protection. We propose that the complexity of the
      situation in the field of COX-derived mediators should be borne in mind when anti
      inflammatory therapy is required.

PMID- 12504792
TI  - Pyridoxal isonicotinoyl hydrazone analogs induce apoptosis in hematopoietic cells
      due to their iron-chelating properties.
AB  - Analogs of pyridoxal isonicotinoyl hydrazone (PIH) are of interest as iron
      chelators for the treatment of secondary iron overload and cancer. PIH,
      salicylaldehyde isonicotinoyl hydrazone (SIH), and 2-hydroxy-1-naphthylaldehyde
      isonicotinoyl hydrazone (NIH), the toxicity of which vary over two orders of
      magnitude, were selected for a study of their mechanisms of toxicity. PIH analogs
      and their iron complexes caused concentration- and time-dependent apoptosis in
      Jurkat T lymphocytes and K562 cells. Bcl-2 overexpression was partially anti
      apoptotic, suggesting mitochondrial mediation of apoptosis. Since the pan-caspase
      inhibitor zVAD-fmk did not reduce lysosomal and mitochondrial destabilization,
      these events occur upstream of caspase activation. In contrast,
      phosphatidylserine externalization and the development of apoptotic morphology
      were inhibited significantly, indicating the role of caspases in mediating these
      later events. Since overexpression of CrmA had no effect on apoptosis, caspase-8
      is not likely involved. Fe(3+) complexes of SIH and NIH, which accumulated in
      59Fe-labeled mouse reticulocytes during incubation with the chelators, also
      caused apoptosis. BSA, which promotes release of the complexes from cells,
      reduced the toxicity of SIH and NIH, suggesting that the induction of apoptosis
      by PIH analogs involves toxic effects mediated by their Fe(3+) complexes.
      Moreover, analogs of these agents lacking the iron-chelating moiety were non
      toxic.

PMID- 12504793
TI  - Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities.
AB  - Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has
      anticoagulant and antithrombotic activities. Unlike heparin, it shows an
      inhibitory action on the progression and metastasis of malignant tumors, although
      the precise mechanisms have not been elucidated. We have demonstrated previously
      that fucoidan can inhibit tube formation following migration of human umbilical
      vein endothelial cells (HUVEC) and that its chemical oversulfation enhances the
      inhibitory potency. In this study, we tested the hypothesis that fucoidan may
      suppress tumor growth by inhibiting tumor-induced angiogenesis. Both natural and
      oversulfated fucoidans (NF and OSF) significantly suppressed the mitogenic and
      chemotactic actions of vascular endothelial growth factor 165 (VEGF(165)) on
      HUVEC by preventing the binding of VEGF(165) to its cell surface receptor. The
      suppressive effect of OSF was more potent than that of NF, suggesting an
      important role for the numbers of sulfate groups in the fucoidan molecule.
      Consistent with its inhibitory actions on VEGF(165), OSF clearly suppressed the
      neovascularization induced by Sarcoma 180 cells that had been implanted in mice.
      The inhibitory action of fucoidan was also observed in the growth of Lewis lung
      carcinoma and B16 melanoma in mice. These results indicate that the antitumor
      action of fucoidan is due, at least in part, to its anti-angiogenic potency and
      that increasing the number of sulfate groups in the fucoidan molecule contributes
      to the effectiveness of its anti-angiogenic and antitumor activities.

PMID- 12504794
TI  - Human mitochondrial and cytosolic branched-chain aminotransferases are cysteine S
      conjugate beta-lyases, but turnover leads to inactivation.
AB  - The mitochondrial and cytosolic branched-chain aminotransferases (BCAT(m) and
      BCAT(c)) are homodimers in the fold type IV class of pyridoxal 5'-phosphate
      containing enzymes that also contains D-amino acid aminotransferase and 4-amino-4
      deoxychorismate lyase (a beta-lyase). Recombinant human BCAT(m) and BCAT(c) were
      shown to have beta-lyase activity toward three toxic cysteine S-conjugates [S
      (1,1,2,2-tetrafluoroethyl)-L-cysteine, S-(1,2-dichlorovinyl)-L-cysteine, and S-(2
      chloro-1,1,2-trifluoroethyl)-L-cysteine] and toward beta-chloro-L-alanine. Human
      BCAT(m) is a much more effective beta-chloro-L-alanine beta-lyase than two
      aminotransferases (cytosolic and mitochondrial isozymes of aspartate
      aminotransferase) previously shown to possess this activity. BCAT(m), but not
      BCAT(c), also exhibits measurable beta-lyase activity toward a relatively bulky
      cysteine S-conjugate [benzothiazolyl-L-cysteine]. Benzothiazolyl-L-cysteine,
      however, inhibits the L-leucine-alpha-ketoglutarate transamination reaction
      catalyzed by both enzymes. Inhibition was more pronounced with BCAT(m). In the
      presence of beta-lyase substrates and alpha-ketoisocaproate (the alpha-keto acid
      analogue of leucine), no transamination could be detected. Therefore, with an
      amino acid containing a good leaving group in the beta position, beta-elimination
      is greatly preferred over transamination. Both BCAT isozymes are rapidly
      inactivated by the beta-lyase substrates. The ratio of turnover to inactivation
      per monomer in the presence of toxic halogenated cysteine S-conjugates is
      approximately 170-280 for BCAT(m) and approximately 40-50 for BCAT(c).
      Mitochondrial enzymes of energy metabolism are especially vulnerable to
      thioacylation and inactivation by the reactive fragment released from toxic,
      halogenated cysteine S-conjugates such as S-(1,1,2,2-tetrafluoroethyl)-L
      cysteine. The present results suggest that BCAT isozymes may contribute to the
      mitochondrial toxicity of these compounds by providing thioacylating fragments,
      but inactivation of the BCAT isozymes might also block essential metabolic
      pathways.

PMID- 12504795
TI  - Yessotoxin, a novel phycotoxin, activates phosphodiesterase activity. Effect of
      yessotoxin on cAMP levels in human lymphocytes.
AB  - Yessotoxin (YTX) is a novel phycotoxin with an unknown mechanism of action that
      has been reported as cardiotoxic, when injected, but non-toxic if ingested
      orally. In this paper, we studied the effect of YTX on adenosine 3',5'-cyclic
      monophosphate (cAMP) pathway, since this pathway can be a cellular target to this
      toxin as happens in other diarrhetic toxins. We determined cAMP levels by
      enzymeimmunoassay and by using the cAMP dye recombinant fluorescein- and
      rhodamine-labeled protein kinase A, which increases their fluorescence when cAMP
      levels are increased. In the presence of YTX, and after a transient small
      increase, cAMP levels were decreased. This effect was Ca(2+) dependent since in a
      Ca(2+)-free medium YTX increased cAMP levels, but this event was reverted after
      addition of external calcium. YTX also reverted the increase of cAMP induced by
      the adenylyl cyclase activator forskolin. These variations in fluorescence units
      were confirmed when cAMP levels were measured by enzymeimmunoassay, YTX decreases
      cAMP from 52.81+/-3.66 to 44.53+/-4.5 fmol. Phosphodiesterase (PDE) IV
      inhibitors, rolipram or etazolate, did not modify the effect of YTX, however,
      when PDE IV was first inhibited no effect of YTX was observed. On the other hand,
      the PDE III inhibitor milrinone counteracted the effect of YTX, and a similar
      effect was observed with the unspecific PDE I inhibitor chlorpromazine. These
      results point to an effect of YTX on PDE activity. In the presence of YTX, the
      fluorescent PDE substrate Mant-cAMP, increased its rate of hydrolysis, the same
      as the PDE from bovine brain increased the hydrolysis of cAMP substrate. In
      addition, YTX increased interleukin-2 production, which indirectly confirms a
      decrease in cAMP. Although results show a very complex pattern of responses, due
      to the interactions and crosstalks between many systems, results suggest that YTX
      is a PDE activator in the presence of external Ca(2+).

PMID- 12504796
TI  - Effect of metamizol on promyelocytic and terminally differentiated granulocytic
      cells. Comparative analysis with acetylsalicylic acid and diclofenac.
AB  - Metamizol is an analgesic and antipyretic agent that can induce agranulocytosis
      in certain patients. However, its effects on granulocyte viability and
      differentiation have been poorly evaluated. Here we analysed the effects of
      metamizol and its active metabolite, 4-methylaminoantipyrine (MAA), on the
      viability of HL60 promyelocytes and their dimethyl sulphoxide-induced
      differentiated granulocytes. Metamizol and MAA at 75 microM (above the peak of
      plasmatic concentration after 2g intake) did not alter granulocytic
      differentiation of HL60 cells. Only at concentrations above 100 microM, well over
      the pharmacological range, metamizol-induced apoptosis in about 30% of the HL60
      promyelocytes, while HL60-granulocytic terminally differentiated cells were more
      resistant to this apoptotic action. When the effects of metamizol were compared
      with those of acetylsalicylic acid (ASA) and diclofenac on cell viability, at
      equivalent concentrations used in analgesic and antipyretic therapy (75 microM
      for metamizol, and ASA and 3 microM for diclofenac) their apoptotic effects were
      similar. Again, the HL60 promyelocytes were more sensitive to apoptosis than
      granulocytic differentiated cells, as measured by the percentage of sub-G(1)
      cells detected by flow cytometry and by determination of caspase activity as a
      function of poly(ADP-ribose) polymerase cleavage. Furthermore, when human blood
      derived granulocytes were treated with metamizol, MAA, and ASA at 75 microM or
      diclofenac at 3 microM, less than 10% of apoptotic granulocytes were detected,
      whereas at toxicological/suprapharmacological concentrations (10mM), about 90% of
      granulocytes were apoptotic. These results demonstrate that metamizol, MAA, ASA,
      and diclofenac, at pharmacological concentrations, neither affect the
      granulocytic differentiation process nor induce relevant apoptosis on terminally
      differentiated granulocytes.

PMID- 12504797
TI  - The effects of cladribine and fludarabine on DNA methylation in K562 cells.
AB  - The effects of the antileukemic adenosine analogues, 2-chloro-2'-deoxyadenosine
      (cladribine) and 9-beta-D-arabinosyl-2-fluoroadenine (fludarabine), on DNA
      methylation were studied in a cell line K562. It was previously found that both
      drugs inactivated SAH hydrolase, an enzyme which participates in the "active
      methyl" cycle. The study examined the effects of these drugs on three aspects of
      DNA methylation: (i) activity of endogenous C-5 DNA methyltransferase; (ii)
      capacity of genomic DNA (gDNA) to accept methyl groups, transferred from S
      adenosylmethionine by the bacterial methyltransferase, SssI; (iii) estimation of
      changes of methylated cytosine levels in gDNA, using methylation-dependent
      restriction analysis. Cladribine and fludarabine inhibited C-5 DNA
      methyltransferase, with ED(50) values of 3.5 and 47.0 microM, respectively, after
      24hr cell growth in the presence of the drugs. After 48 hr growth of cells with
      cladribine (0.1 microM) or fludarabine (3 microM), the capacity of DNA to accept
      methyl groups, in the presence of exogenous bacterial SssI methylase, increased
      by approximately 1.8 and 1.6 times, respectively, compared to control DNA.
      Digestion of gDNA with endonucleases HpaII and BssHII followed by SssI DNA
      methylation, indicated that cladribine (0.1 microM) reduced the level of
      methylated cytosines in both CpG islands and CCGG sequences, sensitive to HpaII
      restriction enzyme. Inhibition of DNA methylation by fludarabine was observed
      mainly in CpG dinucleotide located within sequences sensitive to HpaII. The
      perturbation of DNA methylation was considered as a complex process. Our findings
      for cladribine and fludarabine should be regarded as an extra element of their
      antileukemic efficacy.

PMID- 12504798
TI  - The involvement of diadenosine 5',5"'-P1,P4-tetraphosphate in cell cycle arrest
      and regulation of apoptosis.
AB  - Diadenosine oligophosphates (Ap(n)A) have been proposed to function as
      intracellular and extracellular signaling molecules in animal cells. Here, we
      have examined the cellular and molecular mechanisms underlying the induction of
      apoptosis by diadenosine 5',5"'-P(1),P(4)-tetraphosphate (Ap(4)A). We have shown
      a dose-dependent apoptotic response in cells treated with Ap(4)A. Flow cytometric
      analysis indicated an involvement of Ap(4)A at an early stage of G1/S arrest. No
      difference in the amount of p21(waf1) was observed in HL60 cells treated with
      Ap(4)A compared to control cells. The level of retinoblastoma protein (pRb)
      dropped dramatically when apoptosis was extensive. The cleavage of pRb was
      abrogated if Ap(4)A-treated cells were incubated with general caspase inhibitor
      zVAD-fmk. Ap(4)A also induced a profound decrease in the level of the Bcl-2
      protein. The lack of effect of Ap(4)A on CDK1 activity indicated that Ap(4)A is
      not involved in "aberrant mitosis". We suggest that in vivo Ap(4)A may play a
      significant role in tumor growth suppression by inducing apoptosis.

PMID- 12504799
TI  - Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to
      cladribine and clofarabine and increased ribonucleotide reductase activity
      contributes to fludarabine resistance.
AB  - Mechanisms of acquired resistance to three purine analogues, 2-chloro-2'
      deoxyadenosine (cladribine, CdA), 9-beta-D-arabinofuranosyl-2-fluoroadenine
      (fludarabine, Fara-A), and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
      (clofarabine, CAFdA) were investigated in a human T-lymphoblastic leukemia cell
      line (CCRF-CEM). These analogues are pro-drugs and must be activated by
      deoxycytidine kinase (dCK). The CdA and CAFdA resistant cell lines exhibited
      increased resistance to the other nucleoside analogues activated by dCK. This was
      also the case for the Fara-A resistant cells, except that they were sensitive to
      CAFdA and guanosine analogues. The CdA and CAFdA resistant cells displayed a
      deficiency in dCK activity (to <5%) while the Fara-A resistant cells showed only
      a minor reduction of dCK activity (20% reduction). The activity of high K(m) 5'
      nucleotidase (5'-NT) (cN-II) using IMP as substrate, was 2-fold elevated in the
      resistant cell lines. The amount of the small subunit R2 of ribonucleotide
      reductase (RR) was higher in the Fara-A resistant cells, which translated into a
      higher RR activity, while CdA and CAFdA cells had decreased activity compared to
      the parental cells. Expression of the recently identified RR subunit, p53R2 full
      size protein, in CAFdA cells was low compared to parental cells, but a protein of
      lower molecular weight was detected in CdA and CAFdA cells. Co-incubation of Fara
      A with the RR inhibitor 3,4-dihydroxybenzohydroxamic acid (didox) enhanced
      cytotoxicity in the Fara-A resistant cells by a factors of 20. Exposure of the
      cells to the nucleoside analogues studied here also caused structural and
      numerical instability of the chromosomes; the most profound changes were recorded
      for CAFdA cells, as demonstrated by SKY and CGH analysis. We conclude that down
      regulation of dCK in cells resistant to CdA and CAFdA and increased activity of
      RR in cells resistant to Fara-A contribute to resistance.

PMID- 12504800
TI  - Development of insulin resistance and reversal by thiazolidinediones in C2C12
      skeletal muscle cells.
AB  - AIM/HYPOTHESIS: The aim of this study was to develop an insulin-resistant cell
      culture model in skeletal muscle cell line by chronic presence of insulin in
      serum-free medium and to determine the effect of thiazolidinediones on insulin
      signaling. METHODS: We differentiated C2C12 in a combination of serum-free medium
      in presence or absence of insulin and determined differentiation by creatine
      kinase activity, myogenin and MyoD expression. The development of insulin
      resistance was determined by tyrosine phosphorylation of insulin receptor and
      insulin receptor substrate-1, phosphatidylinositol 3-kinase activity associated
      with insulin receptor substrate-1 and glucose uptake. We treated the cells with
      50 microM of thiazolidinediones to determine the effect on these parameters.
      RESULTS: C2C12 cells were differentiated normally in the serum-free medium in the
      absence or presence of insulin. Chronic treatment of insulin resulted in reduced
      tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1;
      activation of phosphatidylinositol 3-kinase was impaired and insulin-stimulated
      glucose uptake was reduced. The treatment of insulin-resistant cells with
      thiazolidinediones resulted in the enhancement of insulin signaling pathway by
      increasing tyrosine phosphorylation of insulin receptor, insulin receptor
      substrate-1, phosphatidylinositol 3-kinase activity and glucose uptake.
      CONCLUSION/INTERPRETATION: These results indicate that insulin resistance can be
      developed in C2C12 skeletal muscle cell line. These findings implicate a direct
      mechanism of action of thiazolidinediones on skeletal muscle.

PMID- 12504801
TI  - Effects of glycolipids from spinach on mammalian DNA polymerases.
AB  - We purified the major glycolipids in the class of monogalactosyl diacylglycerol
      (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol
      (SQDG) from a green vegetable, spinach (Spinacia oleracea L.). MGDG was an
      inhibitor of the growth of NUGC-3 human gastric cancer cells, but DGDG and SQDG
      had no such cytotoxic effect. Therefore, we studied MGDG and its monoacyglycerol
      form, monogalactosyl monoacylglycerol (MGMG), in detail. MGMG with one fatty acid
      molecule was obtained from MGDG with two fatty acid molecules by hydrolyzing with
      a pancreatic lipase. MGMG was also found to prevent the cancer cell growth. MGDG
      was a potent inhibitor of replicative DNA polymerases such as alpha, delta and
      epsilon. MGMG inhibited the activities of all mammalian DNA polymerases including
      repair-related DNA polymerase beta with IC(50) values of 8.5-36 microg/mL, and
      the inhibition by MGMG was stronger than that by MGDG. Both MGDG and MGMG could
      halt the cell cycle at the G1 phase, and subsequently induced severe apoptosis.
      The relationship between the DNA polymerase inhibition and the cell growth effect
      by these glycolipids is discussed.

PMID- 12504802
TI  - Vitamin E activates gene expression via the pregnane X receptor.
AB  - Tocopherols and tocotrienols are metabolized by side chain degradation via
      initial omega-oxidation and subsequent beta-oxidation. omega-Oxidation is
      performed by cytochrome P450 (CYP) enzymes which are often regulated by their
      substrates themselves. Results presented here show that all forms of Vitamin E
      are able to activate gene expression via the pregnane X receptor (PXR), a nuclear
      receptor regulating a variety of drug metabolizing enzymes. In HepG2 cells
      transfected with the human PXR and the chloramphenicol acetyl transferase (CAT)
      gene linked to two PXR responsive elements, CAT activity was most strongly
      induced by alpha- and gamma-tocotrienol followed by rifampicin, delta-, alpha-
      and gamma-tocopherol. The inductive efficacy was concentration-dependent; its
      specificity was underscored by a lower response when cotransfection with PXR was
      omitted. Up-regulation of endogenous CYP3A4 and CYP3A5 mRNA was obtained by gamma
      tocotrienol, the most potent activator of PXR, with the same efficacy as with
      rifampicin. This points to a potential interference of individual forms of
      Vitamin E with the metabolism and efficacy of drugs.

PMID- 12504803
TI  - DNA repair mechanisms involved in gemcitabine cytotoxicity and in the interaction
      between gemcitabine and cisplatin.
AB  - The influence of DNA repair mechanisms on the interaction between gemcitabine and
      cisplatin was studied using a panel of Chinese hamster ovary (CHO) cell lines
      deficient in one of the following repair pathways: base excision repair (BER),
      nucleotide excision repair (NER), homologous recombination (HR) and non
      homologous end joining (NHEJ). NER and HR are known to be involved in platinum
      DNA adduct repair. Single agent experiments demonstrated that each of the repair
      deficient cell lines had a similar sensitivity towards gemcitabine as the
      parental cell lines, whereas the NER- and HR-deficient lines showed increased
      sensitivity towards cisplatin. Furthermore, in the parental cell lines, the
      administration sequence cisplatin followed by gemcitabine was synergistic,
      whereas the reversed schedule showed additivity and simultaneous administration
      revealed antagonistic cytotoxicity. In the repair deficient cell lines, using
      this synergistic schedule of cisplatin followed by gemcitabine, loss of synergy
      was observed in the NER- and HR-deficient cell lines. However, the magnitude of
      the effect in the NER-deficient cells was small. The sensitivity to the
      combination of cisplatin and gemcitabine shown by the BER- and NHEJ-deficient
      cell lines did not differ significantly from that of the parental cell line.
      Cellular accumulation of platinum as well as the formation of GG- and AG
      intrastrand adducts in the parental line and in the HR-deficient line were not
      affected by gemcitabine. In conclusion, our results indicate that BER, NER, HR,
      and NHEJ are most likely incapable of modulating the cytotoxicity of gemcitabine,
      and that HR is involved in the synergistic interaction between cisplatin and
      gemcitabine in our cell system.

PMID- 12504804
TI  - Cooperative enhancement of insulinotropic action of GLP-1 by acetylcholine
      uncovers paradoxical inhibitory effect of beta cell muscarinic receptor
      activation on adenylate cyclase activity.
AB  - The cooperative effect of glucagon-like peptide 1 (GLP-1) and acetylcholine (ACh)
      was evaluated in a beta cell line model (BRIN BD11). GLP-1 (20 nM) and ACh (100
      microM) increased insulin secretion by 24-47%, whereas in combination there was a
      further 89% enhancement of insulin release. Overnight culture with 100 ng/mL
      pertussis toxin (PTX) or 10nM PMA significantly reduced the combined
      insulinotropic action (P<0.05 and P<0.001, respectively) and the sole stimulatory
      effects of GLP-1 (PTX treatment; P<0.01) or ACh (PMA treatment; P<0.05). Under
      control conditions, ACh (50nM-1mM) concentration-dependently inhibited by up to
      40% (P<0.001) the 10-fold (P<0.001) elevation of cyclic 3',5'-adenosine
      monophosphate (cAMP) induced by 20 nM GLP-1. The paradoxical inhibitory action of
      ACh was abolished by PTX pre-treatment, suggesting involvement of G(i) and/or
      G(o) G protein alpha subunit. Effects of selective muscarinic receptor
      antagonists on the concentration-dependent insulinotropic actions of ACh (50 nM-1
      mM) on 20 nM GLP-1 induced insulin secretion revealed inhibition by rho-FHHSiD
      (M3 antagonist, P<0.05), stimulation with pirenzepine (M1 antagonist, P<0.001)
      and no significant effects of either methoctramine (M2 antagonist) or MT-3 (M4
      antagonist). Antagonism of M2, M3 and M4 muscarinic receptor effects with
      methoctramine (3-100 nM), rho-FHHSiD (3-30 nM) or MT-3 (10-300 nM) did not
      significantly affect the inhibitory action of ACh on GLP-1 stimulated cAMP
      production. In contrast, M1 receptor antagonism with pirenzepine (3-30 0nM)
      resulted in a concentration-dependent decrease in the inhibitory action of ACh on
      GLP-1 stimulated cAMP production (P<0.001). These data indicate an important
      functional cooperation between the cholinergic neurotransmitter ACh and the
      incretin hormone GLP-1 on insulin secretion mediated through the M3 muscarinic
      receptor subtype. However, the insulinotropic action of ACh was associated with a
      paradoxical inhibitory effect on GLP-1 stimulated cAMP production, achieved
      through a novel PTX- and pirenzepine-sensitive M1 muscarinic receptor activated
      pathway. An imbalance between these pathways may contribute to dysfunctional
      insulin secretion.

PMID- 12504805
TI  - Effects of high glucose on cytokine-induced nerve growth factor (NGF) expression
      in rat renal mesangial cells.
AB  - Nerve growth factor (NGF) accumulates at sites of inflammation and modulates
      local immune reactions. To characterize the mechanisms of cytokine-induced NGF
      expression under physiological and pathophysiological conditions, we have used
      cultured glomerular mesangial cells, which play a key role in glomerular
      inflammatory diseases such as diabetic nephropathy. To study the effects of high
      glucose on cytokine-induced NGF expression, rat mesangial cells were treated with
      the cytokines interleukin-1beta and tumor necrosis factor alpha under normal (1.0
      g/L) and high (4.5 g/L) glucose concentrations. In the presence of high glucose
      concentrations, the cytokines drastically potentiated NGF protein but not mRNA
      expression when compared to physiological glucose levels. The specific protein
      kinase C inhibitors Ro31-8220 and CGP41251 suppressed cytokine-induced NGF
      expression. Moreover, blocking the oxidative activation of the protein kinase C
      pathway by N-acetylcysteine inhibited glucose effects on NGF synthesis.
      Neutralizing antibodies against transforming growth factor-beta inhibited
      cytokine-induced NGF expression under normal glucose concentrations but not under
      high glucose conditions. Enhanced expression of NGF under high glucose conditions
      may contribute to kidney diseases such as diabetic nephropathy.

PMID- 12504806
TI  - Inhibition of cytokine production by the herbicide atrazine. Search for nuclear
      receptor targets.
AB  - The hematological toxicity of the commonly used triazine herbicides is a cause
      for concern. In a search for molecular targets of these compounds, as their
      effects paralleled those seen with dexamethasone (DEX), we first looked for
      interaction with the glucocorticoid receptor. In contrast to the effects on
      proliferation and cytokine production of DEX, those induced by atrazine were not
      prevented by the glucocorticoid antagonist RU486. Also, whereas DEX was able to
      inhibit the promoter activity of genes regulated by NF-kappaB, atrazine failed to
      do so. We next looked for interaction with members of the peroxisome proliferator
      activated receptor (PPAR) family. No peroxisome proliferation was observed in the
      liver or kidneys of mice treated with atrazine. Moreover, no PPAR-mediated
      induction of promoter activity was seen on targets of PPARalpha, PPARgamma, or
      PPARdelta. Similarly, neither atrazine nor simazine were able to stimulate
      RORalpha-mediated promoter activity. Finally, no binding of atrazine to the AR
      was observed. In conclusion, the effects of atrazine-type herbicides most
      probably do not result from interaction with the above-mentioned nuclear
      receptors.

PMID- 12504807
TI  - Sex, drugs and arrhythmia: are gender differences in risk of torsades de pointes
      simply a matter of testosterone?

PMID- 12504808
TI  - Altered phosphorylation and Ca2+-sensitivity of myofilaments in human heart
      failure.

PMID- 12504809
TI  - Biological activities of fibroblast growth factor-2 in the adult myocardium.
AB  - Fibroblast growth factor-2 (FGF-2) is a potent regulator of many cellular
      functions and phenomena, including cell proliferation, differentiation, survival,
      adhesion, migration, motility and apoptosis, and processes such as limb
      formation, wound healing, tumorigenesis, angiogenesis, vasculogenesis and blood
      vessel remodeling. In the adult myocardium, FGF-2 is expressed by various cell
      types, including cardiomyocytes, fibroblasts and smooth muscle cells. The
      biological effects of FGF-2 in the myocardium are mediated by the high-affinity
      tyrosine kinase receptor FGFR-1, the major FGF receptor in the heart. Here, we
      give an overview of current insights into the multiple roles of FGF-2 in the
      myocardium, as they pertain to two basic phenomena: ischemia-reperfusion injury
      and cardiac hypertrophy. The first category includes roles for FGF-2 in
      cardioprotection, the inflammatory response, angiogenesis and vascular
      remodeling, while the second includes myocyte hypertrophy, fibrosis, and gap
      junction functioning (conduction). Given the strong evidence for FGF-2 as both a
      cardioprotective and angiogenic agent, the therapeutic potential of FGF-2 in the
      ischemic myocardium is discussed.

PMID- 12504810
TI  - Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation.
AB  - The cardiac SR Ca(2+)-ATPase (SERCA2a) regulates intracellular Ca(2+)-handling
      and thus, plays a crucial role in initiating cardiac contraction and relaxation.
      SERCA2a may be modulated through its accessory phosphoprotein phospholamban or by
      direct phosphorylation through Ca(2+)/calmodulin dependent protein kinase II
      (CaMK II). As an inhibitory component phospholamban, in its dephosphorylated
      form, inhibits the Ca(2+)-dependent SERCA2a function, while protein kinase A
      dependent phosphorylation of the phospho-residues serine-16 or Ca(2+)/calmodulin
      dependent phosphorylation of threonine-17 relieves this inhibition. Recent
      evidence suggests that direct phosphorylation at residue serine-38 in SERCA2a
      activates enzyme function and enhances Ca(2+)-reuptake into the sarcoplasmic
      reticulum (SR). These effects that are mediated through phosphorylation result in
      an overall increased SR Ca(2+)-load and enhanced contractility. In human heart
      failure patients, as well as animal models with induced heart failure, these
      modulations are altered and may result in an attenuated SR Ca(2+)-storage and
      modulated contractility. It is also believed that abnormalities in Ca(2+)-cycling
      are responsible for blunting the frequency potentiation of contractile force in
      the failing human heart. Advanced gene expression and modulatory approaches have
      focused on enhancing SERCA2a function via overexpressing SERCA2a under
      physiological and pathophysiological conditions to restore cardiac function,
      cardiac energetics and survival rate.

PMID- 12504811
TI  - In vivo androgen treatment shortens the QT interval and increases the densities
      of inward and delayed rectifier potassium currents in orchiectomized male
      rabbits.
AB  - OBJECTIVES: Women have longer rate-corrected QT intervals (QTc) and are at higher
      risk for developing life-threatening torsades de pointes ventricular arrhythmias
      than men, especially after taking medications that block cardiac human ether-a-go
      go-related gene (HERG)-encoded K(+) channels. The purpose of the present study
      was to determine if the male sex steroid hormone, dihydrotestosterone (DHT),
      influences QT intervals in orchiectomized (Orch) male rabbits. METHODS: ECG and
      whole-cell patch-clamp analyses were employed to evaluate cardiac repolarization
      and K(+) currents in hearts isolated from orchiectomized (Orch) male New Zealand
      White rabbits receiving subcutaneous sustained release pellets for either
      dihydrotestosterone (DHT) or placebo. The efficacy of the treatment paradigm was
      monitored by measuring plasma DHT concentrations before and after the treatment
      period (10-14 days). RESULTS: The results show that rate- and drug-induced QT
      lengthening is attenuated in hearts from DHT-treated rabbits relative to placebo
      treated controls. No significant changes in QRS were observed in response to DHT,
      thereby indicating that DHT influences QT primarily through an effect on
      ventricular repolarization. In addition, hearts from DHT-treated rabbits
      displayed significantly less QT lengthening in response to quinidine challenge
      compared to placebo controls. Current densities for two important cardiac
      repolarizing K(+) currents, I(K1) and I(Kr), were found to be significantly
      increased in ventricular myocardium of DHT-treated rabbits. Further, the half
      maximal voltage of activation (V(1/2)) for I(Kr) was significantly shifted to
      more negative potentials in myocytes from DHT vs. placebo hearts (21.2+/-1.2 vs.
      30.2+/-1.4 mV, respectively, n=12, P<0.001). Corresponding changes in rabbit
      ether-a-go-go-related gene (RERG) mRNA were not found when examined by Northern
      blot hybridization. CONCLUSIONS: These results suggest that the presence of male
      sex steroid hormones in male rabbits helps to suppress rate- and drug-induced
      delays in cardiac repolarization. DHT action produces increased current densities
      for I(K1) and I(Kr) and a left-shift in the V(1/2) for I(Kr) that could account,
      at least in part, for the observed QTc differences between males and females.
      Since little change was seen in ventricular RERG gene expression, DHT action in
      the heart may influence I(Kr) via post-transcriptional and/or post-translational
      mechanisms.

PMID- 12504812
TI  - Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart
      failure results from altered phosphorylation of contractile proteins.
AB  - OBJECTIVE: The alterations in contractile proteins underlying enhanced Ca(2+)
      sensitivity of the contractile apparatus in end-stage failing human myocardium
      are still not resolved. In the present study an attempt was made to reveal to
      what extent protein alterations contribute to the increased Ca(2+)-responsiveness
      in human heart failure. METHODS: Isometric force and its Ca(2+)-sensitivity were
      studied in single left ventricular myocytes from non-failing donor (n=6) and end
      stage failing (n=10) hearts. To elucidate which protein alterations contribute to
      the increased Ca(2+)-responsiveness isoform composition and phosphorylation
      status of contractile proteins were analysed by one- and two-dimensional gel
      electrophoresis and Western immunoblotting. RESULTS: Maximal tension did not
      differ between myocytes obtained from donor and failing hearts, while Ca(2+)
      sensitivity of the contractile apparatus (pCa(50)) was significantly higher in
      failing myocardium (deltapCa(50)=0.17). Protein analysis indicated that neither
      re-expression of atrial light chain 1 and fetal troponin T (TnT) nor degradation
      of myosin light chains and troponin I (TnI) are responsible for the observed
      increase in Ca(2+)-responsiveness. An inverse correlation was found between
      pCa(50) and percentage of phosphorylated myosin light chain 2 (MLC-2), while
      phosphorylation of MLC-1 and TnT did not differ between donor and failing hearts.
      Incubation of myocytes with protein kinase A decreased Ca(2+)-sensitivity to a
      larger extent in failing (deltapCa(50)=0.20) than in donor (deltapCa(50)=0.03)
      myocytes, abolishing the difference in Ca(2+)-responsiveness. An increased
      percentage of dephosphorylated TnI was found in failing hearts, which
      significantly correlated with the enhanced Ca(2+)-responsiveness. CONCLUSIONS:
      The increased Ca(2+)-responsiveness of the contractile apparatus in end-stage
      failing human hearts cannot be explained by a shift in contractile protein
      isoforms, but results from the complex interplay between changes in the
      phosphorylation status of MLC-2 and TnI.

PMID- 12504813
TI  - Beneficial effects of combination of ACE inhibitor and angiotensin II type 1
      receptor blocker on cardiac remodeling in rat myocardial infarction.
AB  - OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitor and angiotensin II type
      I receptor blockers (ARB) prevent cardiac remodeling after myocardial infarction
      (MI). However, it is controversial whether combination therapy of ACE inhibitor
      and ARB is more effective on cardiac remodeling than each agent alone. In this
      study, we compared the effects of an ACE inhibitor (temocapril), an ARB (CS-866),
      and their combination on cardiac remodeling after MI. METHODS: Temocapril at 3 or
      30 mg/kg/day, CS-866 at 1 or 10 mg/kg/day, or combined temocapril and CS-866 at
      1.5 and 0.5 mg/kg/day or at 15 and 5 mg/kg/day, respectively, were administered
      to rats after MI. At 4 weeks after MI, we assessed hemodynamics, cardiac function
      by Doppler echocardiography and non-infarcted myocardial mRNA expression.
      RESULTS: Animals treated with a combination of the two drugs had hemodynamics,
      heart weights and dimensions similar to the other treated animals. However, the
      combination of the two drugs suppressed ANP, BNP and other gene expressions
      related to contractile proteins of fetal type and collagens more effectively than
      ACE inhibitor or ARB alone. CONCLUSION: These data suggest that combination of
      the two drugs, independent of the hemodynamic effect, may improve left
      ventricular phenotypic change, collagen accumulation and diastolic function.

PMID- 12504814
TI  - Attenuation of myocardial ischemia/reperfusion injury in mice with myocyte
      specific overexpression of endothelial nitric oxide synthase.
AB  - OBJECTIVE: The role of nitric oxide (NO) in myocardial ischemia/reperfusion
      injury remains controversial as both NO donors and NO synthase (NOS) inhibitors
      have shown to be protective. We generated transgenic (TG) mice that overexpress
      endothelial NOS (eNOS) exclusively in cardiac myocytes to determine the effects
      of high cardiac NO levels on ischemia/reperfusion injury and cellular Ca(2+)
      homeostasis. Wild-type (WT) mice served as controls. METHODS: Hearts were
      perfused in vitro and subjected to 20 min of total no-flow ischemia and 30 min of
      reperfusion (n=5 per group). Left ventricular function, cGMP levels and
      intracellular Ca(2+) transients (Ca(2+)(i)) were determined. RESULTS: Left
      ventricular pressure was reduced (maximum, -33%) and basal cardiac cGMP was
      increased (twofold) in TG hearts, and the changes were reversed by NOS blockade
      with N(G)-nitro-L-arginine methyl ester (L-NAME). Relative to baseline, recovery
      of reperfusion contractile function was significantly better in hearts from TG
      (98%) than WT (51%) mice, and L-NAME abolished this effect. Heart rate and
      coronary perfusion pressure were not different between groups. Systolic and
      diastolic Ca(2+)(i) concentrations were similar in WT and TG hearts, but
      Ca(2+)(i) overload during early reperfusion tended to be less in TG hearts.
      Kinetic analysis of pressure curves and Ca(2+)(i) transients revealed a faster
      left ventricular diastolic relaxation and abbreviated aequorin light signals in
      TG hearts at baseline and during reperfusion. CONCLUSIONS: High levels of NO/cGMP
      strongly protect against ischemia/reperfusion injury, the protection is largely
      independent of changes in Ca(2+)(i) modulation, but relates to reduced
      preischemic performance. Myocyte-specific NO augmentation may aid in studies of
      the (patho)physiological roles of cardiac-derived NO.

PMID- 12504815
TI  - Transmyocardial laser revascularization preserves regional myocardial perfusion:
      an MRI first pass perfusion study.
AB  - OBJECTIVE: It is controversial whether transmyocardial laser revascularization
      (TMLR) improves myocardial perfusion. Therefore, we assessed myocardial perfusion
      before and after TMLR with quantitative magnetic resonance perfusion imaging
      (MRPI) in an animal study. METHODS: One week after partial occlusion of the left
      circumflex artery (LCx) in 12 pigs, resting perfusion (ml/g/min), perfusion
      reserve (PR) with adenosine, regional wall thickening (RWT), cardiac output (CO)
      were quantified with MRI in the LCx (lateral) and LAD (septal) dependent
      myocardium. Subsequently, six animals were treated with TMLR of the lateral left
      ventricle (LV). Six animals were left untreated. A final MR was performed 8 weeks
      later. MRPI data were compared to microsphere-derived blood flow and % LV
      necrosis (TTC). 'Normal' myocardial perfusion was assessed with MRPI in 12 non
      instrumented animals. RESULTS: Resting perfusion prior to TMLR (0.7-0.9+/-0.3) in
      the LV-lateral myocardium was preserved after TMLR (1.0+/-0.3) and decreased
      without TMLR (0.3+/-0.1, P<0.05). There was a significant difference (P<0.01)
      between the TMLR treated and untreated group. Compared to 'normals' (1.2+/-0.2)
      perfusion of the LV-lateral wall was not different after TMLR but reduced
      (P<0.02) without TMLR. PR was not different between TMLR-treated (1.4+/-0.9) and
      untreated (1.9+/-0.6) group but was reduced (P<0.04) compared to PR of 'normals'
      (2.7+/-0.8). MRPI data and microsphere-derived perfusion were significantly
      correlated (P<0.01). RWT in the LCx-dependent myocardium improved (P<0.02) after
      TMLR. CO decreased (P<0.02) and TTC-staining indicated more LV-necrosis without
      TMLR (6.6+/-1.6 vs. 3.7+/-1.5, P<0.01). CONCLUSION: TMLR preserves regional
      myocardial perfusion and improves function as shown with MRPI.

PMID- 12504816
TI  - Combined phospholamban ablation and SERCA1a overexpression result in a new
      hyperdynamic cardiac state.
AB  - OBJECTIVE: Phospholamban ablation or ectopic expression of SERCA1a in the heart
      results in significant increases in cardiac contractile parameters. The aim of
      the present study was to determine whether a combination of these two genetic
      manipulations may lead to further augmentation of cardiac function. METHODS:
      Transgenic mice with cardiac specific overexpression of SERCA1a were mated with
      phospholamban deficient mice to generate a model with SERCA1a overexpression in
      the phospholamban null background (SERCA1(OE)/PLB(KO)). The cardiac phenotype was
      characterized using quantitative immunoblotting, sarcoplasmic reticulum calcium
      uptake and single myocyte mechanics and calcium kinetics. RESULTS: Quantitative
      immunoblotting revealed an increase of 1.8-fold in total SERCA level, while
      SERCA2 was decreased to 50% of wild types. Isolated myocytes indicated increases
      in the maximal rates of contraction by 195 and 125%, the maximal rates of
      relaxation by 200 and 124%, while the time for 80% decay of the Ca(2+)-transient
      was decreased to 43 and 75%, in SERCA1(OE)/PLB(KO) hearts, compared to SERCA1a
      overexpressors and phospholamban knockouts, respectively. These mechanical
      alterations reflected parallel alterations in V(max) and EC(50) for Ca(2+) of the
      sarcoplasmic reticulum Ca(2+) transport system. Furthermore, there were no
      significant cardiac histological or pathological alterations, and the myocyte
      contractile parameters remained enhanced, up to 12 months of age. CONCLUSIONS:
      These findings suggest that a combination of SERCA1a overexpression and
      phospholamban ablation results in further enhancement of myocyte contractility
      over each individual alteration.

PMID- 12504817
TI  - What happens when cardiac Na channels lose their function? 1--numerical studies
      of the vulnerable period in tissue expressing mutant channels.
AB  - OBJECTIVE: The vulnerable period (VP) defines an interval during which premature
      impulses can trigger reentrant arrhythmias leading to ventricular fibrillation
      and sudden death. The mechanistic basis of the success or failure of impulse
      propagation during the VP remains unclear. Recent clinical reports of gene
      mutations, drugs and cardiac disease link a variety of often lethal conditions
      with loss of cardiac Na channel function (NaLOF) and reentrant proarrhythmia. We
      hypothesized that during the VP, the Na conductance at the stimulus site is
      graded and that NaLOF would favor reentry specifically by flattening this
      gradient, which would destabilize antegrade front formation. METHODS: Using
      numerical studies of propagation in a one-dimensional cable of ventricular cells,
      we identified the boundaries of the VP using paired (s1-s2) stimulation. We
      explored VP alterations associated with different NaLOF scenarios including
      reduced channel density, accelerated rate of inactivation, and prolonged recovery
      from inactivation. RESULTS: Following the passage of a wave over the s2 site, a
      gradient in the restoration of Na channel conductance was demonstrated to exist
      during the VP. The VP boundaries coincided with different thresholds for stable
      retrograde and antegrade impulse propagation. Reducing channel density,
      accelerating inactivation and slowing the recovery from inactivation flattened
      the restoration gradient and extended the VP. VP extension was directly
      proportional to the time constant of Na channel recovery. CONCLUSIONS: Mutations
      that accelerate inactivation, slow recovery from inactivation, or reduce Na
      channel density flatten the restoration gradient within the VP which prolongs the
      VP and increases the probability that a premature impulse will initiate reentry.
      These studies define a new mechanism that links alterations in Na channel
      function with conditions that enable premature excitation to generate
      proarrhythmia and sudden death.

PMID- 12504818
TI  - Changes in distinct species of 1,2-diacylglycerol in cardiac hypertrophy due to
      energy metabolic disorder.
AB  - OBJECTIVE: The juvenile visceral steatosis (JVS) mouse, a genetic model of
      systemic carnitine deficiency resulting from carnitine transport mutation,
      develops cardiac hypertrophy. We determined two putative lipid messengers, 1,2
      diacylglycerol (DAG) and ceramide, in JVS and carnitine palmitoyltransferase-I
      (CPT-I) inhibitor etomoxir-treated mice because these lipids function as co
      messengers in the myocardium via modification of protein kinase C activity.
      METHODS: JVS mice were evaluated at 4 and 8 weeks of age. The effect of long-term
      etomoxir treatment (45 mg/day) (ET) on mice was investigated in control mice from
      4 to 8 weeks of age. As a model of inhibited cardiac hypertrophy, carnitine
      treated JVS (CT) mice were produced. Myocardial DAG and ceramide levels and their
      fatty acid composition were measured. RESULTS: The heart/body weight ratio
      increased by 100% in JVS mice compared with that in controls, while that of CT
      mice was normalized in comparison with controls at 8 weeks of age. DAG markedly
      increased in both JVS and ET mice compared with that in controls (1,677+/-84,
      1,258+/-49, and 585+/-58 ng/dry wt, respectively; P<0.01 for controls versus JVS
      or ET mice), whereas it was decreased significantly in CT mice compared with that
      in JVS mice (1,066+/-54 ng/dry wt, P<0.01). Furthermore, the fatty acid
      composition of DAG was similar in JVS and ET mice; in particular, 18:1 and 18:2
      were significantly elevated in the myocardium (P<0.01 versus controls). On the
      other hand, that of DAG in CT mice was similar to that of the control group. In
      contrast, no difference was observed in myocardial ceramide levels among the
      groups. CONCLUSIONS: Pharmacological intervention with etomoxir mimics changes in
      the lipid second messenger characteristic of genetic JVS mice. The results
      suggest that the increases in distinct DAG species might be involved in the
      pathogenesis of cardiac hypertrophy as a result of disorder of fatty acid
      transport.

PMID- 12504819
TI  - Chronic amiodarone-induced inhibition of the Na+-K+ pump in rabbit cardiac
      myocytes is thyroid-dependent: comparison with dronedarone.
AB  - OBJECTIVE: To examine the thyroid-dependence of the effect of amiodarone on the
      sarcolemmal Na(+)-K(+) pump, and the effect on the pump of dronedarone, a
      deiodinated amiodarone congener without influence on thyroid status. METHODS: New
      Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or
      thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na(+)-K(+)
      pump current was measured using the whole-cell patch-clamp technique in isolated
      ventricular myocytes. Pump current was also measured in myocytes isolated from a
      separate group of rabbits not subjected to thyroidectomy but treated with
      dronedarone, or placebo for 3 weeks. RESULTS: Treatment of thyroidectomised
      rabbits with amiodarone caused a significant prolongation of the corrected QT
      interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in
      myocytes isolated from thyroidectomised rabbits was significantly lower than pump
      current in myocytes from sham-operated controls. However, treatment of
      thyroidectomised rabbits with amiodarone did not cause any additional decrease in
      pump current. Treatment with dronedarone caused prolongation of QT(c). However,
      it had no effect on Na(+)-K(+) pump current. CONCLUSIONS: The inhibitory effect
      of amiodarone on Na(+)-K(+) pump current is thyroid-dependent, whereas the
      effects on heart rate and QT(c) are at least partially mediated by thyroid
      independent mechanisms. In contrast to its parent compound, dronedarone has no
      significant effects on the activity of the Na(+)-K(+) pump.

PMID- 12504820
TI  - Endothelin-1 induced proinflammatory markers in the myocardium and leukocytes of
      guinea-pigs: role of glycoprotein IIB/IIIA receptors.
AB  - AIM: To assess whether endothelin-1 (ET-1) induces the in vivo expression of
      inflammatory-related proteins, namely cyclooxygenase-2 (COX-2) and tissue factor,
      in the myocardium and circulating leukocytes of guinea-pigs. The involvement of
      platelets was also analyzed. METHODS: ET-1 (0.013 microg/min) was infused to male
      guinea-pigs for 45 min in the presence and absence of tirofiban, a nonpeptidic
      blocker of the glycoprotein IIb/IIIa receptor (GPIIb/IIIa). Tissue factor and COX
      2 expression were determined by Western blot. RESULTS: No changes in mean
      arterial pressure and heart rate were detected. ET-1-infused guinea-pigs showed a
      marked increase in the number of platelets expressing activated GPIIb/IIIa
      receptors (0.8+/-0.03% vs. 6.5+/-0.2%; P<0.05). Tirofiban (10 microg/Kg bw/min)
      blunted ex vivo platelet aggregation in response to ADP, although only partially
      reduced COX-2 and tissue factor expression in both the myocardium and leukocytes
      of ET-1-infused guinea-pigs. The myocardium of platelet-depleted guinea-pigs also
      showed a reduced COX-2 expression after ET-1 infusion (57+/-3% reduction;
      P<0.05). In vitro studies demonstrated that platelets (10(7) and 10(9)
      platelets/well) enhanced ET-1 (10(-7) mol/l)-induced COX-2 expression in heart
      slices. CONCLUSION: ET-1 stimulated in vivo the expression of the pro
      inflammatory proteins COX-2 and tissue factor in the myocardium and in leukocytes
      by a mechanism GPIIb/IIIa platelet receptors.

PMID- 12504821
TI  - Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and
      susceptibility to Fas-mediated apoptosis in cardiac myocytes.
AB  - OBJECTIVE: Fas ligand (FasL) is a key cytokine which initiates apoptosis when
      FasL binds to its receptor, Fas. Cardiac myocytes are generally resistant to Fas
      induced apoptosis. However, sublethal dose of doxorubicin (Dox) can sensitize
      cardiac myocytes to Fas-induced apoptosis. We investigated the molecular
      mechanism by which Dox sensitizes cardiac myocytes to Fas-induced apoptosis.
      FLICE inhibitory protein (FLIP) is a key molecule for blocking Fas-induced
      apoptosis by functioning as a caspase-8 dominant negative. METHODS AND RESULTS:
      FLIP was constitutively expressed in cultured neonatal rat cardiac myocytes. FLIP
      protein levels were markedly down-regulated by Dox in a time-dependent and dose
      dependent manner. Next, we examined the relation of reactive oxygen species (ROS)
      by Dox to the expression of FLIP. Both of N-acetylcysteine (NAC) and the
      combination of superoxide dismutase and catalase restored the decreased FLIP in
      Dox-treated cardiac myocytes to the basal level. NAC also restored the increased
      formation of thiobarbituric acid-reactive substance after Dox-treatment.
      Concurrently, the susceptibility to Fas-mediated apoptosis disappeared with the
      treatments of the antioxidant agents. Hydrogen peroxide down-regulated FLIP in a
      dose-dependent fashion and also sensitized cardiac myocytes to Fas-induced
      apoptosis. CONCLUSIONS: FLIP, an inhibitor of apoptosis induced by cytokines of
      TNF family, contributes at least partly to Dox-induced sensitization to Fas
      mediated apoptosis in cardiac myocytes. The expression of FLIP in cardiac
      myocytes is regulated by ROS.

PMID- 12504822
TI  - The functional role of the JAK-STAT pathway in post-infarction remodeling.
AB  - OBJECTIVES: Recently, the Janus kinase/signal transducer and activator of
      transcription (JAK-STAT) signaling pathway was found to be prominently associated
      with activation of the autocrine loop of the heart tissue-localized renin
      angiotensin system (RAS). We investigated if the JAK-STAT pathway is activated in
      the post-myocardial infarction (MI) non-ischemic myocardium (NIM), destined to
      undergo remodeling and whether blockade of the pathway in vivo can modify early
      post-MI remodeling. METHODS: We investigated the time course of tyrosine
      phosphorylation of JAK-STAT and gp130 proteins in the NIM of post-MI rat heart as
      well as the binding activity of STAT proteins to the St-domain of the
      angiotensinogen gene promoter. We further compared the effects of in vivo
      blockade of RAS by the AT(1) receptor (AT(1)R) blocker losartan with the in vivo
      blockade of JAK-STAT pathway by the specific JAK2 blocker tyrphostin AG490 on
      certain aspects of early post-MI remodeling. RESULTS: We showed that JAK2, STATs
      1, 3, 5a and 6 and gp130 proteins are tyrosine phosphorylated as early as 5-30
      min post-MI and that STATs 1, 3, and 5a remain activated up to 7 days post-MI.
      Gel mobility shift assay showed a strong binding activity of STAT proteins to the
      St-domain of angiotensinogen gene promoter in 1-day post-MI NIM. The binding was
      significantly reduced in rat hearts previously treated with losartan or
      tyrphostin AG490. Supershift experiments identified STATs 3 and 5a as
      specifically interacting with the St-domain. Both AT(1)R and JAK2 blockade
      resulted in significant amelioration of the increase of protein phosphatase 1
      activity and decrease in basal level of p16-phospholamban that may underlie early
      diastolic dysfunction, as well as partial amelioration of early downregulation of
      Kv4.2 gene expression that may underlie increased arrhythmogenicity of 3-day post
      MI heart. On the other hand, while blockade of AT(1)R significantly ameliorated
      apoptotic changes in 1-day post-MI border zone, blockade of JAK2 increased
      apoptosis. CONCLUSIONS: The study provides compelling evidence in favor of the
      linkage of the JAK-STAT pathway with the angiotensin II autocrine loop and
      uncovers a mechanism by which selective activation of a set of STAT proteins
      underlies mobilization of the gene activation program intrinsic to post-MI
      remodeling. It also suggests that drugs that inhibit JAK-STAT phosphorylation may
      provide a new approach to modify post-MI remodeling. This needs to be confirmed
      in long term in vivo studies in the post-MI heart.

PMID- 12504823
TI  - Protein kinase C betaII activation induces angiotensin converting enzyme
      expression in neonatal rat cardiomyocytes.
AB  - OBJECTIVE: Members of the protein kinase C (PKC) family are important mediators
      of cell signaling underlying multiple aspects of myocardial function. Activation
      of the betaII isoform of PKC is thought to be involved in the development of
      congestive heart failure. To investigate the biological effect of PKC-betaII, we
      measured gene expression of angiotensin converting enzyme (ACE) and angiotensin
      II (AngII) receptors AT(1A) and AT(1B) in cardiomyocytes overexpressing PKC
      betaII. METHODS: An adenovirus construct expressing PKC-betaII was introduced
      into cultured neonatal rat ventricular myocytes (NRVMs). Western blot and in situ
      kinase assay was used to measure PKC-betaII level and activity in NRVMs. Real
      time quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      analysis was used to measure the mRNA levels of several genes following PMA
      stimulation of either un-infected or ad-PKC-betaII infected cells. RESULTS: Our
      data show that activation of PKC-betaII in cardiomyocytes leads to elevated
      expression of angiotensin-converting enzyme (ACE) gene. Treatment of adeno-PKC
      betaII infected cardiomyocytes with phorbol 12-myristate 13-acetate (PMA)
      resulted in an 8-fold increase of ACE mRNA expression, whereas ACE mRNA levels
      only increased around 2-fold in uninfected or adeno-GFP (green fluorescent
      protein) infected cardiomyocytes with similar PMA treatment. The induction of ACE
      mRNA was blocked by the PKC-beta-specific antagonist LY379196. No significant
      change of angiotensin II receptors AT1a and AT1b could be detected in the
      cardiomyocytes expressing PKC-betaII. CONCLUSION: These data indicate that ACE is
      a transcription target of PKC-betaII activation in cardiomyocytes, and also
      suggest a mechanism for the involvement of PKC in cardiac hypertrophy and
      fibrosis through increased activity of angiotensin converting enzyme in the
      myocardium.

PMID- 12504824
TI  - Mitochondrial DNA mutations activate the mitochondrial apoptotic pathway and
      cause dilated cardiomyopathy.
AB  - OBJECTIVE: To determine whether low frequency mitochondrial DNA (mtDNA) mutations
      are pathogenic. METHODS: We studied mice that express a proofreading-deficient
      mitochondrial DNA polymerase in the heart and develop cardiac mtDNA mutations.
      RESULTS: At 4 weeks of age, when point mutation levels had risen to on average
      two per mitochondrial genome, these mice developed severe dilated cardiomyopathy.
      Interstitial fibrosis first became apparent at 4 weeks of age and progressed with
      age. Sporadic myocytic death occurred in all regions of the heart, apparently due
      to apoptosis as assessed by histological analysis and TUNEL staining. The
      frequency of TUNEL-positive cells peaked at 4-5 weeks of age and then gradually
      declined. While mitochondrial respiratory function, ultrastructure, and number
      remained normal, cytochrome c was released from mitochondria, a known apoptotic
      signal. CONCLUSION: mtDNA mutations therefore are pathogenic, and seem to trigger
      apoptosis through the mitochondrial pathway.

PMID- 12504825
TI  - Discoordinate re-expression of cardiac fetal genes in N(omega)-nitro-L-arginine
      methyl ester (L-NAME) hypertension.
AB  - OBJECTIVE: Hypertension produced by chronic inhibition of nitric oxide (NO)
      synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) was used to determine
      the effect of severe pressure overload with or without left ventricular (LV)
      hypertrophy on the transcriptional activation of the cardiac fetal genes encoding
      for the natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain
      natriuretic peptide (BNP), and for beta-myosin heavy chain (MHC) in both atrial
      and ventricular muscle. A previously reported association of LV hypertrophy with
      the activation of cardiac renin and angiotensin-converting enzyme (ACE) in this
      hypertension model was also investigated. METHODS: Male Sprague-Dawley rats
      received L-NAME (75 mg/kg/day) or were left untreated for 4 (n=12) or 8 (n=12)
      weeks. RESULTS: L-NAME-treated rats became severely hypertensive in both
      treatment groups but only five out of 12 8-week treatment animals showed a
      significantly increased LV weight to body weight (BW) ratio (LVW/BW). LV ANF
      mRNA, but not LV BNP mRNA, correlated significantly with LVW/BW only in animals
      showing LV hypertrophy. No changes were observed in atrial gene expression or
      plasma concentration of ANF or BNP. A significant correlation was found between
      LVW/BW and LV renin mRNA and LV ACE activity in rats with LV hypertrophy. LV beta
      MHC mRNA levels were significantly increased in the LV of rats with or without LV
      hypertrophy at both 4 and 8 weeks of treatment. CONCLUSIONS: It is concluded that
      pressure overload per se does not promote NP or cardiac renin-angiotensin system
      gene expression while increased beta-MHC expression is a marker of LV pressure
      overload even in the absence of LV hypertrophy. It is apparent that L-NAME causes
      a disruption in the coordinated transcriptional activation of cardiac fetal genes
      expected of hypertrophic stimuli acting on the LV.

PMID- 12504826
TI  - Simvastatin reduces NF-kappaB activity in peripheral mononuclear and in plaque
      cells of rabbit atheroma more markedly than lipid lowering diet.
AB  - OBJECTIVE: To study whether simvastatin reduces inflammation in atherosclerosis
      beyond its hypolipidemic effects. METHODS: Twenty-four rabbits with induced
      femoral injury and on an atherogenic diet were randomized to normolipidemic diet
      (n=9), or to continue the atherogenic diet while receiving simvastatin 5
      mg/kg/day (n=9) or no treatment (n=6) for 4 weeks. RESULTS: As compared with no
      treatment, the normolipidemic diet significantly reduced lipid levels, while
      simvastatin produced nonsignificant reductions. In spite of this, NF-kappaB
      binding activity in peripheral mononuclear cells was reduced in the simvastatin
      group [2,958+/-5,123 arbitrary units (a.u.)] as compared with no treatment
      (49,267+/-20,084 a.u.; P<0.05) and normolipidemic groups (41,492+/-15,876 a.u.;
      P<0.05) (electrophoretic mobility shift assay). NF-kappaB activity in the
      atherosclerotic lesions was also reduced by simvastatin as compared to nontreated
      animals (4,108+/-3,264 vs. 8,696+/-2,305 nuclei/mm(2); P<0.05), while the
      normolipidemic diet induced only a nonsignificant diminution (P>0.05)
      (Southwestern histochemistry). Similarly, simvastatin decreased macrophage
      infiltration (4.6+/-12 vs. 19+/-12% of area staining positive; P<0.05) and the
      expression of interleukin-8 (24+/-12 vs. 63+/-21%; P<0.05) and metalloproteinase
      3 (16+/-3 vs. 42+/-28%; P<0.05) (immunohistochemistry), while the reduction
      achieved by normolipidemic diet in all these parameters was again nonsignificant
      (P>0.05). CONCLUSIONS: These findings suggest that simvastatin reduces
      inflammation in atherosclerotic plaques and in blood mononuclear cells more than
      expected for the lipid reduction achieved.

PMID- 12504827
TI  - Effects of local MCP-1 protein therapy on the development of the collateral
      circulation and atherosclerosis in Watanabe hyperlipidemic rabbits.
AB  - OBJECTIVE: The objective of our study was to quantify the arteriogenic potency of
      Monocyte Chemoattractant Protein-1 (MCP-1) under hyperlipidemic conditions.
      Additionally, we aimed to determine the effects of locally applied MCP-1 on
      systemic serum lipid levels as well as on atherosclerosis. METHODS: A total of
      sixty-four Watanabe rabbits was treated with either low dose MCP-1 (1
      microg/kg/week), high dose MCP-1 (3.3 microg/kg/week) or PBS as a control
      substance. Substances were applied directly into the collateral circulation via
      an osmotic minipump with the catheter placed in the proximal stump of the ligated
      femoral artery. Either 1 week or 6 months after initiation of the treatment X-ray
      angiography was performed as well as measurements of collateral conductance using
      fluorescent microspheres. The extent of atherosclerosis was quantified in whole
      aortas using Sudan IV staining. RESULTS: One week after ligation of the femoral
      artery a significant increase in collateral conductance was observed in animals
      treated with high dose MCP-1 (control: 2.2+/-0.8 ml/min/100 mmHg vs. MCP-1 high
      dose: 8.9+/-2.0 ml/min/100 mmHg, P<0.05). Six months after femoral artery
      ligation no differences were found between the treated and the control group
      (PBS; 44.9+/-11.6 ml/min/100 mmHg, MCP-1; 47.8+/-11.5 ml/min/100 mmHg, P=NS). No
      influence was found on serum lipids or on the development of atherosclerosis in
      the present model. CONCLUSION: MCP-1 accelerates arteriogenesis upon femoral
      artery ligation under hyperlipidemic conditions. Six months after treatment these
      pro-arteriogenic effects of MCP-1 can no longer be observed. The present data do
      not show an effect of local MCP-1 treatment on serum lipids or on
      atherosclerosis. It should be noted however that a high standard deviation was
      observed for the data on atherosclerotic surface area, necessitating additional
      experiments in a different model of atherosclerosis.

PMID- 12504828
TI  - Genistein supplementation stimulates the oxytocin system in the aorta of
      ovariectomized rats.
AB  - OBJECTIVE: In the present study, we localized oxytocin (OT) and its receptor
      (OTR) in the rat aorta, and investigated whether genistein, an isoflavonic
      phytoestrogen, influences their expression in ovariectomized (OVX) rats deficient
      in estrogen. METHODS AND RESULTS: OVX Sprague-Dawley rats were randomized to the
      following groups: genistein (from 0.02 to 5 microg/g/day, s.c. for 10 days),
      estradiol (E(2,) 0.1 microg/g/day, s.c. for 10 days) or their respective
      vehicles. OT and OTR immunostaining was concentrated in the aortic tunica intima,
      suggesting their paracrine/autocrine action within endothelial cells. Reverse
      transcription-polymerase chain reaction analysis showed that 1 and 5 microg/g but
      not 0.1 microg/g genistein elevated OT mRNA (2-fold P<0.05), OTR mRNA (2.5-fold,
      P<0.05) and endothelial nitric oxide synthase (eNOS) mRNA (2-fold, P<0.05) in the
      aorta of OVX rats. In addition, genistein treatment increased estrogen receptor
      alpha (ERalpha) (2- to 3-fold, P<0.05) but resulted in a 50% decrease of ERbeta
      (P<0.05). These genistein effects were neutralized by treatment of OVX rats with
      the ER antagonist ICI 182,780 (1.5 microg/g/day, s.c. for 10 days). Similarly,
      Western blot analysis revealed an increase of 67-kDa OTR, 140-kDa eNOS, 62-kDa
      ERalpha and a decrease of 55-kDa ERbeta (P<0.05) in the aorta of OVX rats treated
      with genistein. In contrast, the treatment of OVX rats with E(2) elevated ERbeta
      mRNA (1.5 fold, P<0.05) but similarly to genistein increased OT, OTR, eNOS and
      ERalpha mRNA. CONCLUSION: These results provide the first evidence of OT and OTR
      co-localization in endothelial cells. The response to genistein via ER activation
      can be regarded as a recovery from endothelial dysfunction induced by
      ovariectomy.

PMID- 12504829
TI  - A Rho-associated kinase mitigates reperfusion-induced change in the shape of
      cardiac capillary endothelial cells in situ.
AB  - OBJECTIVE: We have previously demonstrated that ischaemia and reperfusion of the
      myocardium alter capillary dimensions and endothelial cell shape and that these
      changes are likely to be effected by the actomyosin contractile system in
      endothelial cells. Rho GTPases are involved in the regulation of cytoskeletal re
      organization and in cell contraction. Rho-associated kinase regulates the
      sensitivity of myosin light chain to Ca(2+) in smooth muscle but not in cardiac
      or skeletal muscle myocytes. This study investigated the role of Rho-associated
      kinase in endothelial cell shape change induced by cardiac ischaemia and
      reperfusion. The role of Rho proteins in endothelial cell shape change in situ in
      the myocardial capillary bed has to date not been investigated. METHODS:
      Ischaemia and reperfusion were induced in Langendorff perfused rat hearts at
      constant flow. Electron microscopy and immunofluorescence studies localized the
      beta Rho-associated kinase isotype in capillary endothelial cells. Whole
      capillary and luminal cross-section areas, luminal and abluminal membrane lengths
      were measured to monitor changes in cell dimensions. We used a ROCK inhibitor, Y
      27632, to investigate the role of this protein in endothelial cell shape change.
      RESULTS: ROCK1 localized primarily to intracellular membranes in endothelial
      cells. Morphometric analysis and a study of capillary lumen resin casts
      demonstrated that inhibition of the activity of this kinase with Y-27632 ablated
      the change in shape of endothelial cells induced by ischaemia and reperfusion.
      CONCLUSION: These results suggest that ROCK1 is involved in cardiac capillary
      endothelial cell shape change in situ and that targeting the contractile system
      in this way may be useful in ameliorating reperfusion injury.

PMID- 12504830
TI  - NO contributes to EDHF-like responses in rat small arteries: a role for NO
      stores.
AB  - OBJECTIVES: Responses to EDHF are usually characterised in the presence of nitric
      oxide synthase (NOS) and cyclooxygenase (COX) inhibitors. The contribution of NO
      to endothelium-dependent relaxation in the presence of NOS inhibitors was
      assessed using NO scavengers with the objective of testing (i) whether any
      residual NO produces endothelium-dependent relaxation in a manner similar to EDHF
      and (ii) to identify the source of the residual NO. METHODS: Small rat hepatic
      and mesenteric arteries were mounted in a tension myograph for either isometric
      or membrane potential measurements. RESULTS: Relaxation to ACh was unaffected by
      pre-treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 300 microM), and
      indomethacin (Indo, 5 microM) in the absence or presence of 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM), nitro-L-arginine (300
      microM) or L-nitro-mono-methyl-arginine (L-NMMA, 300 microM). Addition of OxyHb
      (20 microM) or carboxy-PTIO (300 microM) produced a significant suppression of
      ACh-induced relaxations ( approximately 40%). In L-NAME+Indo treated arteries ACh
      induced hyperpolarisation (delta16.3+/-2.1 mV, n=8) was significantly suppressed
      with the addition of OxyHb (Delta10.2+/-1.6 mV, n=12). ACh-induced relaxation, in
      the presence of L-NAME+Indo+OxyHb, was abolished by raised extracellular K(+), or
      the combination of charybdotoxin (CTX, 100 nM)+apamin (100 nM). In contrast
      whilst L-NAME+indo+barium+ouabain suppressed ACh-induced relaxation, the presence
      of OxyHb had no additional effect. Ultraviolet light induced a relaxation in
      arteries treated with L-NMMA+Indo (37.0+/-5.2%, n=9) which was sensitive to OxyHb
      (15.2+/-10.9%, n=4), and barium+ouabain (6.39+/-2.7%, n=4), but not CTX+apamin
      (37.8+/-2.4%, n=4). CONCLUSIONS: These findings suggest that NO contributes
      significantly to the "EDHF-like" response seen in rat small arteries and that the
      source of this NO may be preformed vascular stores.

PMID- 12504831
TI  - Involvement of cyclic AMP-mediated pathway in neural release of noradrenaline in
      canine isolated mesenteric artery and vein.
AB  - OBJECTIVE: Our major hypothesis is that cyclic adenosine-3',5'-monophosphate
      (cAMP)-mediated modulation of neurotransmitter release plays different roles at
      low and high activity of the sympathetic nervous system. We further hypothesize
      that cAMP-mediated neuromodulation might underlie disparate neurovascular control
      in mesenteric arteries and veins. METHODS: Electrical field stimulation (EFS)
      evoked overflow of noradrenaline (NA) was evaluated in the absence or presence of
      activators and inhibitors of cAMP-dependent pathway at low (4 Hz) and high (16
      Hz) frequencies of stimulation of endothelium-denuded secondary and tertiary
      branches of the canine isolated inferior mesenteric arteries and veins. The
      content of NA in samples of the superfusates collected before and during nerve
      stimulation was assayed by high-performance liquid chromatography (HPLC)
      technique in conjunction with electrochemical detection. Student's t-test and
      ANOVA analyses were applied for statistical analysis. RESULTS: Activation of cAMP
      dependent pathway with either isoproterenol (ISO, 10 microM), forskolin (1
      microM), dibutyryl cAMP (100 microM) or combined site-specific activators of cAMP
      dependent protein kinase (PKA) [i.e. N(6)-phenyl-adenosine-3',5'-cyclic
      monophosphate, 8-(6-aminohexyl) aminoadenosine-3',5'-cyclic monophosphate, and
      the Sp-isomer of 5,6-dichloro-1-D-ribofuranosylbenzimidazole-3',5'-cyclic
      monophosphorothioate, each 100 microM] caused an enhancement of the EFS-evoked
      overflow of endogenous NA at 16 Hz of stimulation but was without an effect at 4
      Hz of stimulation both in artery and vein. The EFS (16 Hz)-evoked overflow of NA
      in vein was also increased in the presence of inhibitors of phosphodiesterase
      (PDE) III and PDE IV (i.e. milrinone, 0.4 microM, and roilpram, 30 microM),
      whereas these inhibitors did not affect the overflow of NA in the artery. The
      facilitating effect of activators of cAMP-dependent pathway on the EFS-evoked
      release of NA at 16 Hz appears to be more pronounced in the vein than in artery.
      The increasing effect of ISO (10 microM) was inhibited with either propranolol (1
      microM) or the adenylyl cyclase (AC) inhibitor [9-(tetrahydro-2'-furyl)adenine]
      (SQ 22,536, 100 microM) in both blood vessels. The ISO effect was inhibited by
      the PKA inhibitor 14-22 amide (PKI(14-22)), 1 microM, in the artery but not in
      vein. The enhancing effect of FSK was inhibited by pretreatment of the tissue
      with SQ 22,536, 100 microM, or the PKA inhibitors PKI(14-22), 1 microM, and 4
      cyano-3-methylisoquinoline, 50 nM. However, the inhibitors alone did not
      significantly change the EFS-evoked overflow of NA in both blood vessels.
      CONCLUSIONS: Activation of AC-cAMP-PKA pathway appears to play a role in
      modulating NA release at higher stimulation frequencies as might be expected
      during stress, strenuous exercise, or hemorrhage. The AC-cAMP pathway plays a
      more pronounced role in the autonomic neural control of mesenteric veins than of
      the corresponding arteries, whereas the PKA contribution is more distinct in the
      arteries.

PMID- 12504832
TI  - Paraoxonase-1 reduces monocyte chemotaxis and adhesion to endothelial cells due
      to oxidation of palmitoyl, linoleoyl glycerophosphorylcholine.
AB  - OBJECTIVE: High-density lipoprotein (HDL) is postulated to protect against the
      development of atherosclerosis, in part, by inhibiting the oxidation of low
      density lipoprotein (LDL) in the sub-endothelial space and thus inhibiting
      activation of the endothelium. The HDL-associated enzyme, paraoxonase-1, is
      proposed to be a major protective factor. However, HDL is also prone to oxidation
      when exposed to peroxynitrite and may therefore, once oxidized, have properties
      similar to oxidized LDL. METHODS AND RESULTS: We exposed human HDL to the
      peroxynitrite donor 3-morpholinosydnonimine and incubated oxidized HDL with human
      umbilical vein endothelial cells (HUVECs). Oxidized HDL increased monocyte
      binding (P<0.001) and enhanced chemotaxis (P<0.001). The major oxidized
      phospholipids were 1-palmitoyl (stearoyl)-2-[9-oxo]nanoyl(azelaoyl)-sn-glycero
      phosphocholine, derived from linoleate-containing phosphatidylcholines, and 1
      palmitoyl(stearoyl)-2-[5-oxo]valeroyl(glutaroyl)-sn-glycero-phosphocholine,
      derived from arachidonate-containing phosphatidylcholines. Incubation of HUVECs
      with synthetically prepared 1-palmitoyl-2-[9-oxo]nanoyl(azelaoyl)-sn-glycero
      phosphocholine, or 1-palmitoyl-2-[5-oxo]valeroyl(glutaroyl)-sn-glycero
      phosphocholine increased binding of monocytes (P<0.001) and chemotaxis (P<0.001).
      Purified paraoxonase-1 reduced monocyte adhesion and chemotaxis (P<0.001).
      CONCLUSIONS: (i) HDL can be a source of oxidatively-derived bioactive
      phospholipids; (ii) the fragmented phospholipids with a 9-carbon aldehyde or acid
      are as effective as a 5-carbon aldehyde or acid at inducing monocyte adhesion and
      chemotaxis; and (iii) paraoxonase-1 is effective at reducing the activity of
      these phospholipid oxidation products.

PMID- 12504833
TI  - Adrenomedullin augments the release and production of tissue factor pathway
      inhibitor in human aortic endothelial cells.
AB  - OBJECTIVES: Adrenomedullin (AM) is a hypotensive and vasodilative peptide. It has
      been reported that AM plays several biological roles in cardiovascular and
      endocrine systems, however, effects on the blood coagulation system have not been
      examined. In this study, we examined its effect on tissue factor pathway
      inhibitor (TFPI), which is a potent inhibitor of tissue factor/factor VIIa
      complex-induced coagulation cascade, and is synthesized and constitutively
      secreted by endothelial cells (ECs). The aim of this study was to elucidate the
      effects of AM on release and production of TFPI in ECs. METHODS: Cultured human
      aortic ECs were incubated with AM (10(-14)-10(-6) M), and the antigen levels and
      activity of the free and total form of TFPI after AM exposure were measured in
      culture media using ELISA. Furthermore, receptor interaction and cellular
      signaling of AM were investigated. RESULTS: AM augmented TFPI release and
      production in a dose-dependent manner. The effect on TFPI production was
      inhibited by AM receptor antagonist (AM22-52), the monoclonal antibody against C
      terminal region of AM, MAPKK inhibitor, and cAMP antagonist. CONCLUSION: These
      findings indicate that AM might play an important role in the modulation of
      anticoagulant properties in blood circulation.

PMID- 12504834
TI  - Oxidized-LDL through LOX-1 increases the expression of angiotensin converting
      enzyme in human coronary artery endothelial cells.
AB  - BACKGROUND AND OBJECTIVES: Our previous studies have shown that oxidized low
      density lipoprotein (ox-LDL) and angiotensin II (Ang II) influence each other's
      action in endothelial cells. This study was designed to examine the regulation by
      ox-LDL of the expression of angiotensin converting enzyme (ACE) gene in human
      coronary artery endothelial cells (HCAECs). In addition, we studied the effect of
      the HMG CoA reductase inhibitor simvastatin on this interaction. METHODS AND
      RESULTS: Cultured HCAECs were incubated with ox-LDL (10-80 microg/ml) for 1-24 h.
      Ox-LDL increased the expression of ACE in a concentration- and time-dependent
      fashion. The upregulation of ACE expression in response to ox-LDL was mediated by
      its endothelial receptor LOX-1, since pretreatment of HCAECs with a blocking
      antibody to LOX-1 prevented the expression of ACE (P<0.01). Native-LDL had no
      significant effect on ACE expression. In this process, ox-LDL-induced activation
      of mitogen-activated protein kinase (MAPK p42/44) played an important role, since
      pretreatment of HCAECs with the MAPK p42/44 inhibitor (PD98059, 10 microM)
      inhibited MAPK activation and subsequently attenuated the expression of ACE
      (P<0.01 vs. ox-LDL alone). In other experiments, we pretreated HCAECs with
      simvastatin (10 microM) and then exposed the cells to ox-LDL. Simvastatin
      markedly attenuated ox-LDL-induced MAPK activation, and concurrently reduced ACE
      expression (P<0.01 vs. ox-LDL alone). CONCLUSIONS: Our observations provide
      direct evidence that ox-LDL via LOX-1 activation induces ACE gene expression in
      HCAECs, and MAPK activation plays a signal transduction role in this process.
      Simvastatin, which inhibits MAPK activation, also blocks ox-LDL-mediated
      upregulation of ACE.

PMID- 12504835
TI  - ADMA and oxidative stress are responsible for endothelial dysfunction in
      hyperhomocyst(e)inemia: effects of L-arginine and B vitamins.
AB  - OBJECTIVES: Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular
      disease, and it is associated with endothelial dysfunction. Mechanisms
      responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve
      impaired bioavailability of NO, possibly secondary to accumulation of the
      endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased
      oxidative stress. We investigated whether oral treatment with B vitamins or L
      arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in
      patients with peripheral arterial occlusive disease (PAOD) and
      hyperhomocyst(e)inemia. METHODS: 27 patients with PAOD and hyperhomocyst(e)inemia
      were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin
      B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for
      8 weeks in a double-blind fashion. FDD was determined by high-resolution
      ultrasound in the radial artery. RESULTS: Vitamin B supplementation significantly
      lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1
      micromol/l (P<0.01). However, B vitamins had no significant effect on FDD
      (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In
      contrast, L-arginine treatment did not affect homocyst(e)ine levels, but
      significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of
      elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative
      stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1
      vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks). CONCLUSIONS: Oral
      supplementation with combined B vitamins during 8 weeks does not improve
      endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia,
      whereas L-arginine significantly improved endothelial function in these patients.
      Thus, accumulation of ADMA and increased oxidative stress may underlie
      endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings
      may have importance for evaluation of homocyst(e)ine-lowering therapy.

PMID- 12504836
TI  - HMG-CoA reductase inhibitors promote cholesterol-dependent Akt/PKB translocation
      to membrane domains in endothelial cells.
AB  - OBJECTIVE: Recent results have shown that 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors referred to as statins rapidly activate the
      protein kinase Akt/PKB in endothelial cells (ECs) and endothelial precursor cells
      (EPCs). This pathway is critical for cellular responses that contribute to
      angiogenesis and EC function including nitric oxide production, cellular survival
      and migration. METHODS: Here we tested whether statins control the translocation
      of recombinant and endogenous Akt to the plasma membrane of endothelial cells in
      a cholesterol-dependent manner. RESULTS: Low doses of statins rapidly induce the
      translocation of Akt to discrete sites in endothelial cell plasma membrane that
      colocalize with F-actin-positive, focal adhesion kinase (FAK)-negative
      lamellipodia and filopodia. This translocation event requires the lipid-binding,
      pleckstrin homology domain of Akt. Treatment with phosphoinositide 3-kinase (PI 3
      kinase) inhibitors or the HMG-CoA reductase reaction product L-mevalonate blocks
      the translocation of Akt in response to statin stimulation. Furthermore, the
      ability of statins to promote Akt activation and translocation to the membrane is
      inhibited by cholesterol delivery to cells, but cholesterol loading had no effect
      on VEGF-induced Akt activation. CONCLUSIONS: These results suggest that statin
      activation of Akt signaling is mediated by the translocation of Akt to
      cholesterol-sensitive membrane structures within activated ECs.

PMID- 12504837
TI  - Chimeric DNA-RNA hammerhead ribozyme targeting PDGF A-chain mRNA specifically
      inhibits neointima formation in rat carotid artery after balloon injury.
AB  - OBJECTIVE: Restenosis of the coronary artery after percutaneous transluminal
      coronary angioplasty (PTCA) occurs in 30-50% of patients and remains a major
      clinical problem. We developed ribozyme that targets platelet-derived growth
      factor (PDGF) A-chain mRNA as a gene therapy for restenosis after PTCA. Thus, we
      examined the effects of a chimeric DNA-RNA ribozyme targeting PDGF A-chain mRNA
      on neointima formation in rat carotid artery after balloon injury and evaluated
      its specificity for PDGF A-chain mRNA by microarray analysis. METHODS: Rat
      carotid artery was injured with a 2F Fogarty catheter, and PDGF A-chain specific
      ribozyme was delivered to the injured artery with polyethylenimine. Two weeks
      after injury, the artery was removed, and the intima/media (I/M) ratio was
      evaluated. Six hours after injury, mRNA was extracted with oligo dT cellulose,
      and expression of PDGF A-chain mRNA was evaluated by reverse transcription
      polymerase chain reaction. Expression of PDGF-AA protein was evaluated by Western
      blot analysis. Expression of 970 genes was evaluated by microarray (GeneChip,
      Affimetrix Inc). RESULTS: FITC-labeled ribozyme was taken up into the midlayer
      smooth muscle of the carotid artery until 24 h after balloon injury. Two and 5
      microg of ribozyme significantly reduced neointima formation by 44 and 55% of
      control levels, respectively, in a dose-dependent manner. Ribozyme markedly
      inhibited expression of PDGF A-chain mRNA as well as production of PDGF-AA
      protein in injured vessels. Microarray analysis revealed that expression of 525
      genes was increased after balloon injury. These genes included FLK-1, interleukin
      1 receptor, retinoic acid receptor alpha2 isoform, heat shock protein, MAP kinase
      kinase, Fas antigen, G6Pase, PI-5-P-kinase, p38 MAP kinase, proliferating cell
      nuclear antigen, transforming growth factor-beta, extracellular signal-related
      kinase, and fibroblast growth factor receptor. With respect to expression of
      cytokine and growth factor mRNAs, the best ribozyme specifically inhibited
      expression of PDGF A-chain mRNA. CONCLUSIONS: Our chimeric DNA-RNA hammerhead
      ribozyme targeting PDGF A-chain mRNA inhibited neointima formation in rat carotid
      artery after balloon injury with specific inhibition of expression of PDGF A
      chain mRNA, suggesting that this ribozyme may be useful for therapy of restenosis
      of coronary artery after PTCA.

PMID- 12504838
TI  - Endothelin receptor blockade lowers plasma aldosterone levels via different
      mechanisms in primary aldosteronism and high-to-normal renin hypertension.
AB  - BACKGROUND: Endothelin (ET)-1 contributes to raising blood pressure (BP) and
      inducing cardiovascular disease by vasoconstriction and potent stimulation of
      aldosterone secretion. In the rat this latter effect occurs via ET(B) receptors;
      in humans in vitro studies implicated both ET(A) and ET(B) receptors, but there
      is no conclusive evidence in vivo. METHODS: We recruited 13 consenting
      hypertensive patients: six with primary aldosteronism (PA) and seven with high-to
      normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min
      for 5 min followed by 100 nmol/min for 10 min) of the ET(A)-selective antagonist
      BQ-123 either alone or, on a different day, together with an identical dose of
      the ET(B)-selective antagonist BQ-788. Plasma aldosterone, cortisol and ACTH
      concentration and plasma renin activity (PRA) were measured with radioimmunoassay
      at -15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively.
      RESULTS: BQ-123 alone and combined with BQ-788 significantly lowered mean BP in
      both PA and HNRH patients (by 6-10 mmHg at nadir; P<0.01). In PA patients, a
      short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (
      14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by
      either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788
      lowered aldosterone (-39 and -28%, respectively) and PRA (-43 and -16%,
      respectively), while cortisol and ACTH were unaffected. CONCLUSIONS: Endogenous
      ET-1 contributes to maintaining the high BP values and the aldosterone secretion
      in both PA and HNRH patients. In the former patients, the aldosterone
      secretagogue effect of ET-1 is mediated via ET(B) receptors, while in the latter
      it occurs mainly via ET(A)-mediated stimulation of renin production.

PMID- 12504839
TI  - Maternal and postnatal vitamin D ingestion influences rat aortic structure,
      function and elastin content. [Cardiovasc. Res. 2002;55:369-374].

PMID- 12504842
TI  - Resveratrol--a prostate cancer chemopreventive agent?
AB  - The incidence of prostate cancer in Western countries continues to rise. Whilst
      opinion remains divided on the best treatment for localized disease, intervention
      for metastatic, hormone-independent cancer remains extremely limited. The concept
      of chemoprevention is gaining popularity as an effective means of reducing the
      burden of prostate cancer on the population, and many compounds with putative
      chemopreventive activity are currently under investigation. Resveratrol is a
      plant-derived polyphenolic compound which has a wide spectrum of biological
      activity. It has anti-oxidant and anti-inflammatory properties, and may induce
      apoptosis as well as modulate the function of the androgen receptor in prostate
      cancer cell lines. Further studies to evaluate the use of this compound as a
      chemopreventive agent in prostate cancer are warranted.

PMID- 12504843
TI  - TNP-470 combined with nicardipine suppresses in vivo growth of PC-3, a human
      prostate cancer cell line.
AB  - We examined effects of TNP-470 with or without nicardipine on in vivo or in vitro
      growth of a hormone-independent human prostate carcinoma cell line, PC-3. TNP-470
      (30 mg/kg, daily) or nicardipine (25 microg/kg, daily) alone had little effects
      on in vivo growth of PC-3 cells in nude mice, whereas simultaneous administration
      of both agents significantly inhibited the growth of the xenografts. In vitro
      proliferation of PC-3 was not affected by TNP-470 and/or nicardipine. Combination
      of TNP-470 and nicardipine seems beneficial in the treatment of hormone
      refractory prostate cancer.

PMID- 12504844
TI  - Pilot study of sequentially applied doublets in poor-prognosis metastatic
      urothelial cancer.
AB  - To gather preliminary data on the tolerability of "stacking" sequentially applied
      regimens in patients recognized to have a poor prognosis from metastatic
      urothelial cancer. To assess toxicity, especially cumulative myelosuppression and
      peripheral neuropathy, and to characterize the median survival associated with
      this approach in a high-risk cohort. A total of ten patients were registered and
      treated. Eight of the 10 demonstrated a major response to treatment (3 patients
      with complete clinical response, 5 with partial response). The Kaplan-Meier
      estimate of median survival was 13.1 months, which is encouraging given the
      prognostic features of the group. Significantly, we did not appreciate excessive
      toxicity, and found no peripheral neuropathy of grade 3 or greater. We believe
      this experience supports the notion that combining individually optimized
      doublets or triplets will not necessarily be more toxic than multiple cycles of
      the same regimen. Furthermore, we are encouraged to pursue this line of research
      in light of promising levels of anti-cancer activity. It is clear however, that
      even complete responses are all too often short-lived, and that some qualitative
      change in the impact of cytotoxic therapy is required in order to substantially
      improve the survival of patients with metastatic urothelial cancer.

PMID- 12504845
TI  - Primary radiation therapy for localized prostate cancer.
AB  - Prostate cancer in men is similar to breast cancer in women; both cancers rank
      first, respectively, in incidence and are normally responsive to radiation
      therapy. In addition, advances in mammography help detect earlier breast cancers,
      and the development and refinement of prostatic specific antigen (PSA) has
      resulted in early detection of low-stage localized prostate cancers. This has
      generated debate over the proper management of localized prostate cancer. While
      there have not been any controlled, prospective, randomized trials of sufficient
      power to compare the various local therapies, based on the current available
      data, the three commonly used local modalities, surgery, and external beam
      radiation therapy and brachytherapy (radioactive seed implant), have similar
      efficacy controlling the disease up to 10 years in many patients. Technological
      advances in treatment delivery and planning have improved the treatment of
      prostate cancer with external-beam radiotherapy using three-dimensional conformal
      radiotherapy (3DCRT), ultrasound-guided transperineal implant, or intensity
      modulated radiotherapy (IMRT), as well as proton or neutron beam based therapies.

PMID- 12504846
TI  - GLUT14, a duplicon of GLUT3, is specifically expressed in testis as alternative
      splice forms.
AB  - We have identified and cloned GLUT14, a novel member of the glucose transporter
      family. GLUT14 (SLC2A14) maps to chromosome 12p13.3 (17.1M), about 10 Mb upstream
      of GLUT3, with which it shares remarkable identity. Until now GLUT14 was thought
      to be a pseudogene. It consists of 11 exons with a genomic organization similar
      to that of GLUT3 and likely resulted from a duplication of GLUT3. GLUT14 has two
      alternatively spliced forms; the shorter form of GLUT14 (GLUT14-S) consists of 10
      exons and produces a 497-amino-acid protein that is 94.5% identical to GLUT3. The
      long form (GLUT14-L) has an additional exon and codes for a protein with 520
      amino acids that differs from GLUT14-S only at the N-terminus. GLUT14-S/L contain
      12 putative membrane-spanning helices along with sugar-transporter signature
      motifs that have previously been shown to be essential for sugar transport
      activity. The putative glycosylation sites of GLUT14-S/L are present in loop 1.
      In contrast to the expression of GLUT3 in many tissues, both isoforms of GLUT14
      are specifically expressed in testis. The mRNA level of GLUT14 in testis is about
      four times higher than that of GLUT3. Interestingly, the ortholog of GLUT14 is
      not found in mice. The multiple duplications of GLUT genes suggest that the GLUT
      family probably emerged by gene duplications and mutations during evolution in
      different lineages.

PMID- 12504847
TI  - Paradoxical methylation of the tyrosine hydroxylase gene in mouse preimplantation
      embryos.
AB  - The mouse tyrosine hydroxylase (Th) gene is located in an evolutionarily
      conserved imprinted gene cluster on distal chromosome 7. It is associated with a
      CpG island that spans the promoter of the gene. Using a bisulfite sequencing
      method we show that the Th promoter is fully methylated in both male and female
      mouse germ cells and in human spermatozoa, suggesting that it belongs to the
      newly identified category of CpG islands, the similarly methylated regions
      (SMRs). Contrary to other tissue-specific gene sequences, the mouse Th promoter
      escapes the initial wave of genome demethylation during the first few cell
      cycles, but becomes demethylated between the morula and the blastocyst stages.
      This unusual methylation ontogeny may be a characteristic of the SMRs and/or
      related to the localization of the Th gene in an imprinted gene cluster.

PMID- 12504848
TI  - FISH analysis of 142 EGFP transgene integration sites into the mouse genome.
AB  - Production of transgenic animals is an important technique for studying various
      biological processes. However, whether the integration of a particular transgene
      occurs randomly in the mouse genome has not been determined. Analysis by
      fluorescence in situ hybridization of the integration sites of the 142 EGFP (a
      mutant of green fluorescent protein) transgenic lines that we produced showed
      that the transgenes had become incorporated into every mouse chromosome. A single
      integration site was observed in 82.4% of the lines. The concomitant integrations
      of transgene into two different loci were observed in 15 cases (10.6%). In 3
      cases, the transgenic founder mice showed chimerism in integration sites (2.1%).
      Chromosomal translocation was observed in 7 cases (4.9%). Moreover, when we
      statistically analyzed the transgene integration sites of these mouse lines, they
      were shown to distribute unevenly throughout the genome. This is the first report
      to analyze the transgene integration sites by producing more than 100 transgenic
      mouse lines.

PMID- 12504849
TI  - Characterization and imprinting status of OBPH1/Obph1 gene: implications for an
      extended imprinting domain in human and mouse.
AB  - Human 11p15.5, as well as its orthologous mouse 7F4/F5, is known as the
      imprinting domain extending from IPL/Ipl to H19. OBPH1 and Obph1 are located
      beyond the presumed imprinting boundary on the IPL/Ipl side. We determined full
      length cDNAs and complete genomic structures of both orthologues. We also
      investigated their precise imprinting and methylation status. The orthologues
      resembled each other in genomic structure and in the position of the 5' CpG
      island and were expressed ubiquitously. OBPH1 and Obph1 were predominantly
      expressed from the maternal allele only in placenta, with hypo- and not
      differentially methylated 5' CpG islands in both species. These results suggested
      that the imprinting domain would extend beyond the presumed imprinting boundary
      and that methylation of the 5' CpG island was not associated with the imprinting
      status in either species. It remains to be elucidated whether the gene is under
      the control of the KIP2/LIT1 subdomain or is regulated by a specific mechanism.
      Analysis of the precise genomic sequence around the region should help resolve
      this question.

PMID- 12504850
TI  - A 9.1-kb gap in the genome reference map is shown to be a stable
      deletion/insertion polymorphism of ancestral origin.
AB  - We show a mute 9.1-kb gap in the human genome reference map, unraveled by RDA
      studies, to be a worldwide deletion/insertion polymorphism of stable type. The
      molecular and population data presented suggest its origin from a unique
      ancestral transposition event in chromosomal region 22q11.2, overlapping the
      IglambdaV genes at about 450 kb from the cluster of the IglambdaJ-C genes. These
      findings are not meant to be just another report of a polymorphic marker suitable
      for population studies. Rather, we wish to stress that a large number of inborn
      mute gaps may be spread all over the genome and that the many RDA-detected
      microdeletions already available are efficient tools for the discovery of this
      otherwise hidden category of genetic variation. Apart from their possible impact
      on expression of structural genes, mute gaps must be filled for the reference map
      of our genome to be truly completed.

PMID- 12504851
TI  - Genetic and comparative mapping of genes dysregulated in mouse hearts lacking the
      Hand2 transcription factor gene.
AB  - The helix-loop-helix transcription factor HAND2 plays a vital role in the
      development of the heart, limb, facies, and other neural crest-derived
      structures. We used differential display analysis to identify 33 putative HAND2
      regulated ESTs that are differentially expressed in Hand2(-/-) vs wild-type mice.
      We determined the positions on mouse and human genetic maps of 29 of these by
      using the T31 mouse Radiation Hybrid panel, comparison to human genomic sequence,
      and comparative mapping. We examined the conserved chromosomal locations for
      phenotypes that involve development of heart, face, and limb structures that are
      affected by HAND2. One EST mapped to a region of conserved synteny between mouse
      chromosome 2 and human chromosome 10p. RACE analysis extended the sequence and
      identified this cDNA as the mouse ortholog of human nebulette, an actin-binding
      protein expressed in fetal heart. Nebulette was shown to be deleted in DiGeorge
      Syndrome 2 patients with the proximal deletion of human 10p13-p14 that is
      associated with cardiac and craniofacial abnormalities.

PMID- 12504852
TI  - Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding
      transcriptional coactivators: induced expression in mammary epithelial cells.
AB  - The CITED family proteins bind to CBP/p300 transcriptional integrators through
      their conserved C-terminal acidic domain and function as coactivators. The 21-kDa
      mouse Cited4 protein, a novel member of the CITED family, interacted with
      CBP/p300 as well as isoforms of the TFAP2 transcription factor, coactivating
      TFAP2-dependent transcription. The cited4 gene consisted of only a single exon
      located on chromosome 4 at 56.5-56.8 cM flanked by marker genes kcnq4 and scml1.
      Expression of Cited4 protein was strong and selective in embryonic hematopoietic
      tissues and endothelial cells. In adult animals, Cited4 showed strong milk cycle
      dependent induction in pregnant and lactating mammary epithelial cells. Strong
      induction of Cited4 expression was also observed in SCp2 mouse mammary epithelial
      cells during their prolactin-dependent in vitro differentiation. These results
      implied possible roles for Cited4 in regulation of gene expression during
      development and differentiation of blood cells, endothelial cells, and mammary
      epithelial cells.

PMID- 12504853
TI  - A novel muscle-specific enhancer identified within the deletion overlap region of
      two XLDC patients lacking muscle exon 1 of the human dystrophin gene.
AB  - Previous studies point to the involvement of several discrete transcriptional
      enhancers in the modulation of dystrophin gene expression in skeletal and cardiac
      muscle. Analysis of deletion breakpoints in two X-linked dilated cardiomyopathy
      patients with mutations that remove muscle exon 1 identified a 3.2-kb deletion
      overlap region (XLDC3.2) between -1199 and +2057 bp predicted to contain
      regulatory elements essential for dystrophin gene expression in cardiac muscle. A
      novel-sequence-based search strategy was used to identify a 543-bp region
      downstream of muscle exon 1 rich in cardiac-specific transcriptional elements.
      Designated dystrophin muscle enhancer 2 (DME2), this candidate enhancer was seen
      to function in a position- and orientation-independent manner in muscle cell
      lines but not in fibroblasts. As only modest activity was observed in primary
      neonatal rat cardiomyocytes, DME2 is thought to play a role in dystrophin gene
      regulation at later stages of cardiac muscle development.

PMID- 12504854
TI  - MBD3L1 and MBD3L2, two new proteins homologous to the methyl-CpG-binding proteins
      MBD2 and MBD3: characterization of MBD3L1 as a testis-specific transcriptional
      repressor.
AB  - Methylation of cytosines at CpG dinucleotides is essential for mammalian
      development. MeCP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of proteins that
      contain a methyl-CpG binding domain (MBD). Except for MBD4, these proteins are
      involved in gene silencing imposed by methylated DNA. We have identified a human
      gene that codes for a protein that is 42% identical to MBD3 and 38% identical to
      MBD2 but lacks the methyl-CpG binding domain. The recombinant protein does not
      bind to methylated DNA in vitro. The corresponding mouse Mbd3L1 gene was also
      cloned. The MBD3L1 gene is expressed specifically in testis. During
      spermatogenesis, expression of MBD3L1 is observed only in round spermatids,
      suggesting a role for the gene product in the postmeiotic stages of male germ
      cell development. The MBD3L1 protein is localized to discrete areas in the
      nucleus and contains an N-terminal transcriptional repression domain. This
      repression is independent of histone deacetylase inhibition. A homologue of
      MBD3L1, MBD3L2, was also identified and cloned. Expression of MBD3L2 was found in
      germ cell tumors and some somatic tissues. These novel proteins may function as
      counterparts of MBD2 and/or MBD3 in developmental stage-specific transcriptional
      repression.

PMID- 12504855
TI  - Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene,
      BIGM103, encoding a 7-TM protein: identification of a new protein family having
      Zn-transporter and Zn-metalloprotease signatures.
AB  - To identify novel genes induced during innate immune activation, we screened a
      cDNA library prepared from monocytes stimulated with Mycobacterium bovis BCG cell
      wall. A novel transcript with three-protein coding potential was identified, and
      the expressed proteins from individual frames showed distinct intracellular
      localization. Live and heat-killed Mycobacterium, bacterial cell wall, and
      inflammatory cytokines like TNFalpha were found to be potent inducers of the
      transcript. Expression of this gene is very low or undetectable in unstimulated
      monocytes, while a steady expression level was observed during differentiation of
      monocytes to dendritic cells and macrophages. The entire gene consisted of eight
      major exons and was localized on chromosome 4q22-q24, spanning approximately 84
      kb. The main open reading frame of the transcript encoded a putative seven
      transmembrane (TM) protein that showed homology with a number of functionally
      unknown proteins in the database. Further analysis revealed that all of these
      proteins have detectable similarity with the ZIP family of metal transporters. In
      fact, increased accumulation of intracellular Zn(2+) was observed due to the
      expression of BIGM103 in CHO cells. However, the identified proteins are
      structurally unique compared to known ZIP members and they also possess the
      hallmark of Zn-metalloproteases, suggesting a new class of multi-TM protein with
      dual features. Here we present a collection of these proteins and discuss the
      functional aspects of BIGM103, based on our results and current findings on two
      members of the family, Drosophila Catsup and Arabidopsis IAR1.

PMID- 12504856
TI  - Sequence analysis of the ly49 cluster in C57BL/6 mice: a rapidly evolving
      multigene family in the immune system.
AB  - The cytotoxic activity of murine natural killer cells is controlled in part
      through the action of genes belonging to the Ly49 family. Members of this
      multigene family are found in a region on mouse chromosome 6 termed the natural
      killer gene complex. Using data available through public databases, we performed
      sequence analysis of a 620-kb region in C57Bl/6 (B6) mice that contains the Ly49
      genes. The contiguous genomic sequence has allowed us to describe the complete B6
      Ly49 gene repertoire, which includes two recently described genes as well as
      three partial genes. We have shown that the genes in the cluster have evolved
      through a series of large duplication events involving units of one or more genes
      and we have attempted to characterize the nature of the duplication end points.
      Finally, we have used information regarding gene sequence relationships and
      insertion of repetitive elements to construct a model for the evolution of the
      gene cluster. Our study illustrates that the Ly49 cluster represents an example
      of a rapidly evolving gene family, and continued analysis of this region in other
      strains will undoubtedly provide further insight into mechanisms for generating
      genomic diversity.

PMID- 12504857
TI  - Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in
      Schizophrenia 1).
AB  - We cloned the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1), a candidate
      gene for schizophrenia. Disc1 is 3163 nucleotides long and has 60% identity with
      the human DISC1. Disc1 encodes 851 amino acids and has 56% identity with the
      human protein. Disc1 maps to the DISC1 syntenic region in the mouse, and genomic
      structure is conserved. A Disc1 splice variant deletes a portion of Disc1
      beginning at amino acids orthologous to the human truncation. Bioinformatic
      analysis and cross-species comparisons revealed sequence conservation distributed
      across the genes and conservation of leucine zipper and coiled-coil domains in
      both orthologs. In situ hybridization in adult mouse brain revealed a restricted
      expression pattern, with highest levels in the dentate gyrus of the hippocampus
      and lower expression in CA1-CA3 of the hippocampus, cerebellum, cerebral cortex,
      and olfactory bulbs. Identification of Disc1 will facilitate the study of DISC1's
      function and creation of mouse models of DISC1 disruption.

PMID- 12504858
TI  - The protein kinase ERK3 is encoded by a single functional gene: genomic analysis
      of the ERK3 gene family.
AB  - Extracellular signal-regulated kinase 3 (ERK3) is a distantly related member of
      the mitogen-activated protein (MAP) kinase family of serine/threonine kinases.
      Here, we report the characterization of the genomic loci encoding ERK3 in mice
      and humans. The mouse ERK3 gene (Mapk6) spans more than 20 kb and is split into
      six exons. Its structure is similar to that of the human MAPK6 gene, which
      extends over 40 kb. We also identified and characterized a mouse Mapk6 processed
      pseudogene. In humans, database analysis has revealed the presence of six MAPK6
      processed pseudogenes localized on four different chromosomes. We further show
      that the structure of MAPK6 is closely related to that of the gene encoding the
      homologous protein kinase p63(MAPK) (MAPK4), suggesting that the two genes arose
      by duplication. Our analysis demonstrates that the ERK3 subfamily of MAP kinase
      genes is composed of two functional genes, MAPK6 and MAPK4, and several
      pseudogenes.

PMID- 12504859
TI  - PipTools: a computational toolkit to annotate and analyze pairwise comparisons of
      genomic sequences.
AB  - Sequence conservation between species is useful both for locating coding regions
      of genes and for identifying functional noncoding segments. Hence interspecies
      alignment of genomic sequences is an important computational technique. However,
      its utility is limited without extensive annotation. We describe a suite of
      software tools, PipTools, and related programs that facilitate the annotation of
      genes and putative regulatory elements in pairwise alignments. The alignment
      server PipMaker uses the output of these tools to display detailed information
      needed to interpret alignments. These programs are provided in a portable format
      for use on common desktop computers and both the toolkit and the PipMaker server
      can be found at our Web site (http://bio.cse.psu.edu/). We illustrate the utility
      of the toolkit using annotation of a pairwise comparison of the mouse MHC class
      II and class III regions with orthologous human sequences and subsequently
      identify conserved, noncoding sequences that are DNase I hypersensitive sites in
      chromatin of mouse cells.

PMID- 12504860
TI  - A tribute to John R. Sladek, Jr.

PMID- 12504862
TI  - Rotenone neurotoxicity: a new window on environmental causes of Parkinson's
      disease and related brain amyloidoses.

PMID- 12504863
TI  - Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration
      and alpha-synuclein aggregation.
AB  - Previous studies demonstrated that chronic systemic exposure to the pesticide and
      mitochondrial toxin rotenone through jugular vein cannulation reproduced many
      features of Parkinson's disease (PD) in rats, including nigrostriatal
      dopaminergic degeneration and formation of alpha-synuclein-positive cytoplasmic
      inclusions in nigral neurons (R. Betarbet et al., 2000, Nat. Neurosci. 3, 1301
      1306). Although novel and conceptually important, the rotenone model of PD
      suffered from being extremely labor-intensive. The current paper demonstrates
      that these same features of PD can be reproduced by chronic, systemic exposure to
      rotenone following implantation of subcutaneous osmotic pumps. Chronic
      subcutaneous exposure to low doses of rotenone (2.0-3.0 mg/kg/day) caused highly
      selective nigrostriatal dopaminergic lesions. Striatal neurons containing DARPP
      32 (dopamine and cAMP-regulated phosphoprotein) remained intact with normal
      morphology, and NeuN staining revealed normal neuronal nuclear morphology.
      Neurons of the globus pallidus and subthalamic nucleus were spared. Subcutaneous
      rotenone exposure caused alpha-synuclein-positive cytoplasmic aggregates in
      nigral neurons. This new protocol for chronic rotenone administration is a
      substantial improvement in terms of simplicity and throughput.

PMID- 12504864
TI  - Ectopic expression of cell cycle markers in models of induced programmed cell
      death in dopamine neurons of the rat substantia nigra pars compacta.
AB  - There is increasing evidence that proteins normally involved in the cell cycle
      can regulate neuronal programmed cell death (PCD). However, it remains unknown
      whether cell cycle markers are expressed in normal, postmitotic, postmigratory
      neurons undergoing PCD in vivo. We have previously shown that natural cell death
      occurs postnatally in dopamine neurons of the substantia nigra pars compacta
      (SNpc). PCD can be induced postnatally in these neurons either by intrastriatal
      injection of the neurotoxin 6-hydroxydopamine (6-OHDA) or by medial forebrain
      bundle (MFB) axotomy. At the time of induction of death in these models, these
      neurons are long postmitotic and postmigratory. We have studied three cell cycle
      markers in these models: 5-bromo-2'-deoxyuridine (BrdU) incorporation (a marker
      of S phase), cdc2 protein expression (a marker of G2 phase), and expression of
      MPM2 (a marker of M phase), an epitope phosphorylated by cdc2. We report here
      that postmitotic dopaminergic neurons undergoing PCD in the SNpc following 6-OHDA
      and axotomy lesions incorporate BrdU and overexpress cdc2, but do not express
      MPM2. This is the first in vivo evidence that postmitotic dopamine neurons of the
      SNpc undergoing apoptosis express markers for S phase and G2 phase. These results
      raise the possibility that cell cycle regulatory proteins may play a role in the
      demise of dopaminergic neurons in Parkinson's disease, in which PCD has been
      postulated to play a role.

PMID- 12504865
TI  - Neurotrophic and neuroprotective effects of tripchlorolide, an extract of Chinese
      herb Tripterygium wilfordii Hook F, on dopaminergic neurons.
AB  - It has been reported recently that the immunosuppressant FK506 produced
      neurotrophic and neuroprotective effects on dopaminergic neurons in vitro and in
      vivo. We investigated whether tripchlorolide, an immunosuppressive extract of
      Chinese herb Tripterygium wilfordii Hook F, could exert similar neurotrophic and
      neuroprotective effects similar to those of FK506. It was found that
      tripchlorolide promoted axonal elongation and protected dopaminergic neurons from
      a neurotoxic lesion induced by 1-methyl-4-phenylpyridinium ion (MPP+) at
      concentrations of as low as 10(-12) to 10(-8) M. In situ hybridization study
      revealed that tripchlorolide stimulated brain-derived neurotrophic factor (BDNF)
      mRNA expression. In vivo administration of tripchlorolide (1 microg/kg, ip) for
      28 days effectively attenuated the rotational behavior challenged by D
      amphetamine in the model rats by transection of the medial forebrain bundle. In
      addition, tripchlorolide treatment (0.5 or 1 microg/kg/day for 28 days) increased
      the survival of dopaminergic neurons in substantia nigra pars compacta by 50 and
      67%, respectively. Moreover, tripchlorolide markedly prevented the decrease in
      amount of dopamine in the striatum of model rats. Taken together, our data
      provide the first evidence that tripchlorolide acts as a neuroprotective molecule
      that rescues MPP+ or axotomy-induced degeneration of dopaminergic neurons, which
      may imply its therapeutic potential for Parkinson's disease. The underlying
      mechanism may be relevant to its neurotrophic effect and its efficacy in
      stimulating the expression of BDNF.

PMID- 12504866
TI  - Altered proteasomal function in sporadic Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized pathologically by preferential
      degeneration of the dopaminergic neurons in the substantia nigra pars compacta
      (SNc). Nigral cell death is accompanied by the accumulation of a wide range of
      poorly degraded proteins and the formation of proteinaceous inclusions (Lewy
      bodies) in dopaminergic neurons. Mutations in the genes encoding alpha-synuclein
      and two enzymes of the ubiquitin-proteasome system, parkin and ubiquitin C
      terminal hydrolase L1, are associated with neurodegeneration in some familial
      forms of PD. We now show that, in comparison to age-matched controls, alpha
      subunits (but not beta-subunits) of 26/20S proteasomes are lost within
      dopaminergic neurons and 20S proteasomal enzymatic activities are impaired in the
      SNc in sporadic PD. In addition, while the levels of the PA700 proteasome
      activator are reduced in the SNc in PD, PA700 expression is increased in other
      brain regions such as the frontal cortex and striatum. We also found that levels
      of the PA28 proteasome activator are very low to almost undetectable in the SNc
      compared to other brain areas in both normal and PD subjects. These findings
      suggest that failure of the ubiquitin-proteasome system to adequately clear
      unwanted proteins may underlie vulnerability and degeneration of the SNc in both
      sporadic and familial PD.

PMID- 12504867
TI  - Mitochondrial complex inhibitors preferentially damage substantia nigra dopamine
      neurons in rat brain slices.
AB  - Using a rat brain slice preparation, we investigated the role of energy
      impairment on the selective loss of dopamine neurons in the substantia nigra
      (SN). Brain slices (400 microm) were incubated at 35 degrees C for 2 h in the
      presence or absence of mitochondrial complex inhibitors, rotenone, MPP+, 3
      nitropropionic acid, and antimycin A. Slices were also incubated in rotenone with
      excitatory amino acid (EAA) receptor antagonists, MK-801 and CNQX, to determine
      whether rotenone-induced damage was mediated by EAAs. The slices were then fixed,
      recut into 30-microm sections, and immunolabeled for tyrosine hydroxylase (TH) to
      identify catecholamine neurons and to quantify loss of TH-labeled dendrites after
      treatment. Quantitative comparison was made between SN dopamine neurons, in which
      rotenone-induced dendrite loss was severe, and hypothalamic A11 dopamine neurons,
      which were spared. Adjacent sections that were immunolabeled for calbindin or
      stained with cresyl violet also revealed a striking dendritic degeneration of SN
      neurons in rotenone-exposed slices, whereas noncatecholamine neurons, such as
      those in the perifornical nucleus (PeF), were more resistant. Preferential damage
      to SN dopamine neurons was also evident with other mitochondrial complex
      inhibitors, MPP+ and antimycin A. EAA receptor antagonists provided partial
      protection to SN neurons in slices incubated with rotenone (3 microM). The
      particular vulnerability of SN dopamine neurons in the slice is consistent with
      the vulnerability of SN in Parkinson's disease. The selective effect of
      mitochondrial complex inhibition in SN dopamine neurons implies a fundamental
      deficit in the capacity of these neurons to defend against toxic insult.

PMID- 12504868
TI  - Methamphetamine potentiates HIV-1 Tat protein-mediated activation of redox
      sensitive pathways in discrete regions of the brain.
AB  - Tat is a major regulatory protein encoded by human immunodeficiency viral genome,
      which has been implicated in the pathogenesis of HIV infection, including
      neurologic complications associated with this disease. In addition, drug abuse
      has been identified as a major risk factor of HIV infection. We hypothesize that
      abusive drugs, such as methamphetamine (METH), can directly influence specific
      molecular processes that can further contribute to toxic effects of Tat. To
      elucidate the molecular signaling pathways of Tat- and/or METH-induced toxicity,
      we investigated the effects of a single injection of Tat (25 microg/microl into
      the right hippocampus) and/or METH (10 mg/kg, intraperitoneally) on the
      generation of cellular oxidative stress, DNA-binding activity of specific redox
      responsive transcription factors, and expression of inflammatory genes.
      Administration of Tat or METH resulted in stimulation of cellular oxidative
      stress and activation of redox-regulated transcription factors in the cortical,
      striatal, and hippocampal regions of the mouse brain. In addition, DNA-binding
      activities of NF-kappaB, AP-1, and CREB in the frontal cortex and hippocampus
      were more pronounced in mice injected with Tat plus METH compared to the effects
      of Tat or METH alone. Intercellular adhesion molecule-1 gene expression also was
      upregulated in a synergistic manner in cortical, striatal, and hippocampal
      regions in mice which received injections of Tat combined with METH compared to
      the effects of these agents alone. Moreover, synergistic effects of Tat plus METH
      on the tumor necrosis factor-alpha and interleukin-1beta mRNA levels were
      observed in the striatal region. These results indicate that Tat and METH can
      cross-amplify their cellular effects, leading to alterations of redox-regulated
      inflammatory pathways in the brain. Such synergistic proinflammatory stimulation
      may have significant implications in HIV-infected patients who abuse drugs.

PMID- 12504869
TI  - The effects of brain-irradiation-induced decreases in hippocampal mitotic
      activity on flurothyl-induced epileptogenesis in adult C57BL/6J mice.
AB  - Previous studies have demonstrated that seizures are potent inducers of mitotic
      activity in the rodent hippocampus. The role of this mitotic activity in
      epileptogenesis currently remains unknown. In the present study, we investigated
      the effect of alterations in hippocampal mitotic activity on changes in seizure
      threshold and phenotype using flurothyl kindling. In flurothyl kindling, eight
      repeated flurothyl-induced generalized forebrain (clonic) seizures result in a
      rapid, progressive, and permanent lowering of the generalized seizure threshold
      in mice and in a slowly evolving increase in the percentage of animals expressing
      forebrain-brain stem (clonic-tonic) seizures when reexposed to flurothyl
      following a 2- to 4-week stimulation-free period. Therefore, flurothyl kindling
      serves as an excellent model for evaluating mechanisms of generalized seizure
      threshold and seizure propagation. To investigate this relationship between
      hippocampal mitotic activity and epileptogenesis, mice were given brain
      irradiation, focused mainly on the hippocampus, bilaterally, and were exposed to
      the flurothyl kindling model of epileptogenesis. Brain irradiation virtually
      eliminated all basal and seizure-induced mitotic activity in the hippocampal
      dentate gyrus of mice. In addition, animals that underwent irradiation and
      flurothyl kindling did not differ from control mice on measures of seizure
      threshold (threshold induction and maintenance) and seizure phenotype. Overall,
      these results suggest that seizure-induced increases in mitotic activity in the
      hippocampal dentate gyrus are not directly related to the processes that underlie
      the shift in behavioral seizure phenotype or in either the induction or the
      maintenance of lowered seizure threshold that is observed in this flurothyl model
      of epileptogenesis.

PMID- 12504870
TI  - Reduced dipsogenic response induced by angiotensin II activation of subfornical
      organ projections to the median preoptic nucleus in estrogen-treated rats.
AB  - The present study was carried out to investigate whether estrogen modulates the
      drinking response induced by activation of angiotensinergic neural pathways from
      the subfornical organ (SFO) to the median preoptic nucleus (MnPO). Microinjection
      of angiotensin II (ANG II, 10(-10) M, 0.2 microl) into the SFO elicited drinking
      in ovariectomized (OVX) female rats that were treated with either propylene
      glycol (PG) vehicle or estrogen benzoate (EB). The amount of water intake induced
      by the ANG II injection was significantly greater in the PG-treated than in the
      EB-treated animals. In both groups of female rats, previous injections of
      saralasin (Sar, 10(-10) M, 0.2 microl), a specific ANG II antagonist, into the
      MnPO resulted in the significant attenuation of the drinking response to ANG II,
      showing that the ANG II-induced drinking response may be mediated in part by the
      angiotensinergic SFO projections to the MnPO. Injections of ANG II (10(-10) M,
      0.2 microl) into the MnPO caused drinking in both groups, while no significant
      difference was found between the groups in the amount of water intake. These
      results suggest that increases in the circulating level of estrogen may attenuate
      the drinking response induced by ANG II activation of the SFO projections to the
      MnPO.

PMID- 12504871
TI  - Both short- and long-acting D-1/D-2 dopamine agonists induce less dyskinesia than
      L-DOPA in the MPTP-lesioned common marmoset (Callithrix jacchus).
AB  - The current concept of dyskinesia is that pulsatile stimulation of D-1 or D-2
      receptors by L-DOPA or short-acting dopamine agonists is more likely to induce
      dyskinesia compared to long-acting drugs producing more continuous receptor
      stimulation. We now investigate the ability of two mixed D-1/D-2 agonists, namely
      pergolide (long-acting) and apomorphine (short-acting), to induce dyskinesia in
      drug-nai;ve MPTP-lesioned primates, compared to L-DOPA. Adult common marmosets
      (Callithrix jacchus) were lesioned with MPTP (2 mg/kg/day sc for 5 days) and
      subsequently treated with equieffective antiparkinsonian doses of L-DOPA,
      apomorphine, or pergolide for 28 days. L-DOPA, apomorphine, and pergolide
      reversed the MPTP-induced motor deficits to the same degree with no difference in
      peak response. L-DOPA and apomorphine had a rapid onset of action and short
      duration of effect producing a pulsatile motor response, while pergolide had a
      slow onset and long-lasting activity producing a continuous profile of motor
      stimulation. L-DOPA rapidly induced dyskinesia that increased markedly in
      severity and frequency over the course of the study, impairing normal motor
      activity by day 20. Dyskinesia in animals treated with pergolide or apomorphine
      increased steadily, reaching mild to moderate severity but remaining
      significantly less marked than that produced by L-DOPA. There was no difference
      in the intensity of dyskinesia produced by apomorphine and pergolide. These data
      suggest that factors other than duration of drug action may be important in the
      induction of dyskinesia but support the use of dopamine agonists in early
      Parkinson's disease, as a means of delaying L-DOPA therapy and reducing the risk
      of developing dyskinesia.

PMID- 12504872
TI  - 1-methyl-4-phenylpyridinium (MPP+) decreases mitochondrial oxidation-reduction
      (REDOX) activity and membrane potential (Deltapsi(m)) in rat striatum.
AB  - Mitochondrial dysfunction has long been implicated in the death of nigrostriatal
      dopaminergic neurons in Parkinson's disease (PD) and its experimental models.
      Here we further analyzed changes in the mitochondrial oxidation-reduction (REDOX)
      activity and membrane potential (Deltapsi(m)) of striatal synaptosomes after the
      infusion of 1-methyl-4-phenylpyridinium (MPP+) into rat striatum. MPP+ (40 nmol)
      treatment produced decreases in mitochondrial REDOX activity and Deltapsi(m) at
      18 h, as measured by fluorometric analysis with both Alamar blue and JC-1
      (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide)
      dyes. At this time point, tyrosine hydroxylase (TH) and dopamine transporter
      (DAT) protein levels were not altered, but both decreased at 7 days after MPP+
      (40 nmol) infusion. Both measures of mitochondrial dysfunction induced by MPP+
      (40 nmol) at 18 h were attenuated, at least in part, by pretreatment with a
      selective dopamine uptake inhibitor GBR-12909 (1-(2-(bis(4
      fluorophenyl)methoxy)ethyl)-4-(3-phenylpropyl) piperazine). In addition, GBR
      12909 partially attenuated MPP+ (40 nmol)-caused a loss of striatal nerve
      terminal as indicated by decreases in TH and DAT immunoreactivities as well as
      dopamine and its metabolites levels. The present study indicates that decreases
      in mitochondrial REDOX activity and Deltapsi(m) may play a role in MPP+ -induced
      dopaminergic neurotoxicity, and further provides that improvement of
      mitochondrial dysfunction may be a better way to slow progressive dopaminergic
      neurodegeneration commonly associated with PD.

PMID- 12504873
TI  - Close axonal injury of rubrospinal neurons induced transient perineuronal
      astrocytic and microglial reaction that coincided with their massive
      degeneration.
AB  - To learn more about the pathophysiology of axonal injury and the significance of
      axon collaterals on the survival of axotomized cord-projection central neurons,
      we studied the survival rate, surrounding astrocytic and microglial reactions,
      and bouton coverage on rat rubrospinal cell bodies following their axonal lesion
      at the brain stem and upper cervical level. The brain stem lesion disconnected
      most rubrospinal neurons from all their targets, while the upper cervical lesion
      spared their supraspinal collaterals. Much higher cell loss accompanied by robust
      astrocytic and microglial reaction was found following brain stem than upper
      cervical lesion starting 4 days postaxotomy. The reaction of astrocytes had
      subsided while microglial reaction remained relatively robust by 10 weeks
      postaxotomy when the cell loss had slowed down. Ultrastructural observation
      revealed that reactive astrocytes covered 40%, an increase from the 20% of
      control, of brain stem-axotomized rubrospinal cell body surface at 4 days and 2
      weeks and returned to normal levels by 10 weeks postlesion. An increase of
      apposition by axons and dendrites and a moderate decrease of round and flattened
      vesicle-containing bouton contacts at 4 days and 2 weeks and returning to normal
      levels at 10 weeks postaxotomy accompanied this. It appears that although axotomy
      induced robust astrocytic reaction around cord-projection central neurons, this,
      unlike their periphery-projection counterparts, failed to effectively strip their
      somatic synapses. In effect, this might in part determine neuronal fate following
      axonal injury.

PMID- 12504875
TI  - Grafts of BDNF-producing fibroblasts rescue axotomized rubrospinal neurons and
      prevent their atrophy.
AB  - We have reported that intraspinal transplants of fibroblasts genetically modified
      to express brain-derived neurotrophic factor (BDNF) promote rubrospinal axon
      regeneration and functional recovery following subtotal cervical hemisection that
      completely ablated the rubrospinal tract. In the present study we examined
      whether these transplants could prevent cell loss and/or atrophy of axotomized
      Red nucleus neurons. Adult rats received a subtotal spinal cord cervical
      hemisection followed by a graft of unmodified fibroblasts or fibroblasts
      producing BDNF into the lesion cavity. One or 2 months later, fluorogold was
      injected several segments caudal to the lesion-transplant site to retrogradely
      label those Red nucleus neurons whose axons have regenerated. Unmodified
      fibroblasts failed to protect against either cell loss or atrophy. Neuron counts
      and soma-size measurements in Nissl-stained preparations showed a 45% loss of
      recognizable neurons and 40% atrophy of the surviving neurons in the injured Red
      nucleus. Grafts of BDNF-producing fibroblasts reduced neuron loss to less than
      15% and surviving neurons showed only a 20% decrease in mean soma size. Soma size
      analysis of fluorogold-labeled Red nucleus neurons indicated that the Red nucleus
      neurons whose axons regenerated caudal to the graft did not atrophy. We conclude
      that fibroblasts engineered ex vivo to secrete BDNF and grafted into a partial
      cervical hemisection promote axon regeneration while reducing cell loss and
      atrophy of neurons in the Red nucleus. These results suggest that transplants of
      genetically engineered cells could be an important tool for delivery of
      therapeutic factors that contribute to the repair of spinal cord injury.

PMID- 12504876
TI  - Development of a corticotropin-releasing factor-mediated effect on the firing
      rate of Purkinje cells in the postnatal mouse cerebellum.
AB  - Corticotropin-releasing factor (CRF), present in climbing and mossy fiber
      afferents to the adult mouse cerebellum, acts as a neuromodulator to enhance the
      spontaneous and amino-acid-induced firing rate of Purkinje cells. CRF also is
      present during development of the mouse cerebellum, at ages that precede
      synaptogenesis, which suggests that it may have a different function during
      development compared to its modulatory role in the adult. The intent of this
      study was to determine when CRF begins to affect the firing rate of Purkinje
      cells as well as the time course over which this effect matures. The earliest
      effect of CRF was elicited at postnatal day (P) 9 at which time a weak
      enhancement in the amplitude of the firing rate was recorded. However, the
      amplitude, time to peak, sustainability, and duration of the response were
      significantly different from that recorded in the older animals or adults. The
      excitatory effect of CRF became stronger and the duration of the response
      increased progressively from P9 until it was adult-like by P20. Purkinje cells in
      the posterior lobe vermis developed a mature response before those in the
      anterior lobe or hemispheres. Data from previous studies have shown that CRF and
      its type 1 receptor are present in the cerebellum before birth and that both
      undergo major reorganization around P10. Taken together, these
      immunohistochemical observations and the present physiologic data indicate that
      CRF does not modulate the activity of Purkinje cells until the peptide begins to
      assume an adult-like distribution in cerebellar afferents.

PMID- 12504877
TI  - The distribution and cellular localization of CRF-R1 in the vermis of the
      postnatal mouse cerebellum.
AB  - The distribution of corticotropin-releasing factor (CRF), the development of CRF
      binding sites, and the age at which application of CRF elicits a physiological
      response have been described previously in the postnatal mouse cerebellum. The
      intent of the present study was to determine the cellular and subcellular
      distribution of the CRF type 1 receptor (CRF-R1) in the vermis of the postnatal
      mouse cerebellum and to correlate these data with those presented in previous
      studies. On P0, CRF-R1 is present in the apical processes of migrating Purkinje
      cells. Between P0 and P8, CRF-R1 immunostaining is confined to a supranuclear
      position in Purkinje cell bodies. Between P9 and P14, the receptor immunolabeling
      circumscribes Purkinje cell nuclei and extends into their primary dendrites. An
      adult-like distribution is achieved between P16 and P21. Between P0 and P14, the
      CRF-R1 antibody also labels processes of migrating GABAergic interneurons that
      are directed toward the pial surface. By P12, labeling begins to circumscribe the
      nucleus of GABAergic cells in the internal granule cell layer. Finally,
      astrocytic processes in the white matter, as well as radial glial processes, show
      focal labeling with the CRF-R1 antibody beginning at P3 and throughout postnatal
      development. A previous study demonstrated that CRF does not elicit a
      physiological response in Purkinje cells until P9. This observation, together
      with the data presented in this study, suggests that the binding of CRF to the
      type 1 receptor may be involved in regulating the development of cerebellar
      neurons and glia immediately after birth, before CRF assumes its function as a
      neuromodulator later in postnatal development and in the adult.

PMID- 12504878
TI  - Cytotoxic potential of proinflammatory cytokines: combined deletion of TNF
      receptors TNFR1 and TNFR2 prevents motoneuron cell death after facial axotomy in
      adult mouse.
AB  - Neural injury is known to trigger inflammatory changes, including the synthesis
      of proinflammatory cytokines such as interleukin-1-beta (IL1beta), tumor necrosis
      factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) [G. Raivich, L. L.
      Jones, C. U. A. Kloss, A. Werner, H. Neumann, and G. W. Kreutzberg, 1998, J
      Neurosci, 18: 5804-5816] that may play a pivotal role in mediating the cellular
      response in the affected brain tissue. Here we examined the effects of transgenic
      deletion of receptors for these cytokines on neuronal cell loss in the adult
      mouse facial motor nucleus after a peripheral, facial nerve cut. Homozygous
      deletion of IL1 receptor 1 (IL1R1), TNF receptor 1 or 2 (TNFR1 or TNFR2), or
      IFNgamma receptor 1 (IFNgammaR1) alone had no effect but combined deletion of
      TNFR1 and TNFR2 caused a striking absence of alphaX beta2 integrin/IBA1-double
      labeled, phagocytic microglial nodules in the axotomized facial motor nucleus 14
      days after nerve cut. Moreover, this combined deletion also led to an almost
      complete prevention of cell loss by Day 29. Additional neuronal cell counts at
      Day 60 revealed a second phase of motoneuron cell disappearance, which did not
      depend on the presence of TNF receptors. However, there was still the same 22%
      difference in the total number of motoneurons between the wild-type and TNFR1 & 2
      deficient mice, underlining the role of TNF ligands and both TNF receptors in
      mediating the early phase of neuronal cell loss after traumatic injury.

PMID- 12504879
TI  - Impact of experimental acute hyponatremia on severe traumatic brain injury in
      rats: influences on injuries, permeability of blood-brain barrier,
      ultrastructural features, and aquaporin-4 expression.
AB  - The effects of acute hyponatremia on severe traumatic brain injury (TBI) in 35
      adult male Sprague-Dawley rats were studied in a replicated focal and diffuse
      injury rat model. Such effects were assessed by the cerebral contusion volume and
      axonal injury (AI) densities, determined by quantitative immunoreactivity of beta
      amyloid precursor protein, by blood-brain barrier (BBB) permeability based on
      endogenous IgG immunostaining, and by ultrastructural features. Significant
      increase of contusion volume (P < 0.05) and of AI in the segment of corpus
      callosum beneath the contusion (P < 0.05) and ipsilateral thalamus (P < 0.05)
      were observed at 4 h postinjury during the hyponatremic phase. No change in BBB
      permeability was observed in the hyponatremia + TBI (HT) groups. Significant
      swelling of perivascular astrocytic foot processes in the HT groups was seen at 4
      h (P < 0.01) and 1 day postinjury (P < 0.01) by quantitative image analysis of
      ultrastructures. However, attenuated swelling of perivascular astrocytic foot
      processes in severely edematous medulla oblongata with simultaneous swelling of
      perikaryal astrocytic processes was observed in the HT 1-day group. The
      ultrastructural features were also correlated with the down-regulation of
      aquaporin-4 (AQP4) mRNA expression (P < 0.05). Results suggest that acute
      hyponatremia acts as one of the secondary insults following severe TBI. Such
      exacerbation may not be attributable to further disruption of BBB permeability,
      but rather to the ischemia resulting from the swelling of perivascular astrocytic
      foot processes impeding microcirculation. Down-regulated AQP4 mRNA expression may
      be one of the molecular mechanisms maintaining water homeostasis in diffusely
      injured brain exposed to acute hyponatremia.

PMID- 12504880
TI  - An example of neural plasticity evoked by putative behavioral demand and early
      use of vibrissal hairs after facial nerve transection.
AB  - Abnormally associated movements inevitably occur after surgical repair of the
      facial nerve. The reason for this postparalytic syndrome is poor navigation of
      regrowing axons. Despite the valuable functional advantage provided by the easily
      detected movement of vibrissae in rats, the major investigative tools for
      establishing the degree of misdirected reinnervation are still electrophysiologic
      recordings and retrograde tracing. In the present study we complemented data from
      pre- and postoperative retrograde labeling (FluoroGold, Fast Blue, DiI) of facial
      motoneurons with an evaluation of whisker movements. Using a video-based motion
      analysis system, we compared the recovery of vibrissae motor performance in
      visually normal and blind rats of the Sprague-Dawley strain. The analysis of
      whisker movement after facial nerve surgery revealed a striking discrepancy
      between morphologic and functional estimates. Whereas retrograde labeling
      displayed poor accuracy of target reinnervation and supernumerary axonal
      branching in both groups, the video-based motion analysis showed a perfect
      recovery of vibrissae movements in the blind rats. Attributing the complete
      recovery of whisker movement in the blind rats to an extraordinary plasticity of
      the facial motoneurons induced by putative behavioral demand and forced overuse,
      we conclude that the video-based analysis of whisker movement is a valuable tool
      for studying the progress in functional recovery.

PMID- 12504881
TI  - Modulation of cell death by mouse genotype: differential vulnerability to
      excitatory amino acid-induced lesions.
AB  - Previously we have demonstrated that mature inbred strains of mice differ
      significantly in their response to kainate-induced cell death. While both C57BL/6
      and FVB/N mice exhibit similar seizure activity in response to kainate, only
      C57BL/6 mice can be characterized as resistant to kainate-induced cell death. To
      examine further the molecular pharmacological basis for this strain difference in
      hippocampal sensitivity, we assessed the ability of the ionotropic glutamate
      receptor agonists, kainic acid (KA), N-methyl-D-aspartate (NMDA), ibotenic acid
      (IBO), and quinolinic acid (QUIN), to promote excitotoxic damage. We examined
      seizure-related behavior and subsequent neurotoxicity in C57BL/6 and FVB/N mice
      following intrahippocampal administration of the kainate receptor agonist, KA,
      the NMDA receptor agonists NMDA or QUIN, or the NMDA and metabotropic glutamate
      receptor agonist, IBO. The time course and extent of cell death in mice were
      evaluated using Nissl and selective silver stains, and Fluoro-Jade, a fluorescent
      marker for dying neurons. In the present study, FVB/N mice were exquisitely
      sensitive to injection of KA at all doses, while susceptibility in C57BL/6 mice
      was dose dependent. In contrast, while hippocampal damage was present in both
      strains at all doses of QUIN, the extent of cell damage was significantly less in
      C57BL/6 mice at low doses (30 and 60 mM). Similarly, IBO administration resulted
      in differences in the extent of cell death when administered at the highest dose
      (126 mM). No strain-dependent differences in cell loss were observed following
      NMDA lesions. These results provide further evidence that susceptibility to
      excitotoxin-induced cell death is highly strain dependent and is kainate and NMDA
      receptor dependent.

PMID- 12504882
TI  - The immunophilin ligand GPI-1046 does not have neuroregenerative effects in MPTP
      treated monkeys.
AB  - Nonimmunosuppressant immunophilin ligands have been shown to have neurotrophic
      properties in rodent models of Parkinson's disease (PD), although little is known
      about the effects of these ligands in primates. The immunophilin ligand, GPI
      1046, promotes the regeneration of dopamine (DA) cells in association with
      functional recovery in rodent models. We explored the regenerative effects of GPI
      1046 in an MPTP primate model of PD. We used single photon emission computed
      tomography (SPECT) and the DA transporter tracer (DAT), [(123)I]beta-CIT, to
      evaluate DAT density and clinical recovery before and after treatment with GPI
      1046 or vehicle. Subsequent histological studies were also performed. No effects
      of GPI-1046 were found on any of these measures. These findings show that GPI
      1046 does not have regenerative effects in MPTP-treated primates and suggest that
      there may be species differences with respect to the trophic effects of GPI-1046
      on nigrostriatal DA neurons.

PMID- 12504883
TI  - Transient ischemia of the retina results in altered retrograde axoplasmic
      transport: neuroprotection with brimonidine.
AB  - In adult rats we have induced retinal ischemia and investigated retrograde axonal
      transport in ganglion cells. The animals received in their left eyes, 1 h prior
      to ischemia, two 5-microl drops of saline or 0.5% brimonidine (BMD). Retinal
      ischemia was induced by transient ligature of the left ophthalmic vessels for 90
      min. One hour or 1 week after ischemia, Fluorogold (FG) was applied to both
      superior colliculi, the animals were processed 1 week after FG application, and
      FG-labeled retinal ganglion cell (RGC) densities were estimated in the right
      control and left experimental retinas. In the left retinas of the saline
      pretreated animals, RGC densities diminished to 39 or 30% of the densities found
      in their right control retinas, 7 or 14 days after ischemia, respectively.
      Because in a previous similar study in which FG was applied 7 days before
      ischemia, the percentages of FG-labeled RGCs were 54 and 48%, 7 and 14 days after
      ischemia, respectively, this suggests that retrograde axonal transport was
      impaired in some surviving RGCs. This was confirmed in an additional group of
      rats in which 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate
      was applied to both SCi 3 weeks before ischemia, and FG was applied to the
      intraorbitally cut optic nerve 9 days after ischemia and 5 days before
      euthanization. In the left retinas of the BMD-pretreated animals, RGC densities
      amounted to 90% of the RGC population 7 or 14 days after ischemia and were
      comparable to those obtained in their contralateral nonischemic retinas. Retinal
      ischemia causes RGC loss and induces alterations of retrograde axonal transport
      in a proportion of surviving RGCs. BMD rescues RGCs from ischemia-induced cell
      death and preserves retrograde axonal transport in surviving RGCs.

PMID- 12504884
TI  - Tyrosine phosphatase inhibition enhances neurotrophin potency and rescues
      nigrostriatal neurons in adult rats.
AB  - Neurotrophic factors regulate a variety of cellular processes, including neuronal
      survival during development and after injury. For instance, brain-derived
      neurotrophic factor (BDNF) can prevent the death of dopaminergic substantia nigra
      neurons in rats. Most neurotrophic factor receptors, such as TrkB for BDNF, are
      tyrosine kinases whose signaling is terminated by protein tyrosine phosphatases
      (PTPs). We tested the idea that inhibition of PTPs, and thus potentially
      enhancement of the efficiency of endogenous trophic factors and their receptors,
      would lead to increased neuronal survival. After a 2-week infusion of the small
      PTP inhibitor molecule peroxovanadium (pVa, pervanadate) close to the substantia
      nigra of adult rats, up to 66% of axotomized substantia nigra neurons had
      survived, compared to only 33% in control rats infused with PBS. PVa most likely
      affected TrkB and/or downstream signaling molecules, as ineffective doses of BDNF
      and pVa had a synergistic effect when given simultaneously, rescuing 82% of the
      neurons. PVa stimulated tyrosine hydroxylase (TH) expression in the noninjured
      substantia nigra but did not prevent axotomy-induced loss of TH. These results
      raise the possibility that PTP inhibition can prevent neuronal death by enhancing
      neurotrophic factor signaling pathways in the adult mammalian nervous system,
      identifies an important role for PTPs in neuronal functioning, and points to a
      novel small molecule treatment approach for neurologic disorders

PMID- 12504885
TI  - Reduced susceptibility of magnocellular neuroendocrine nuclei of the rat
      hypothalamus to transient focal ischemia produced by middle cerebral artery
      occlusion.
AB  - Intraparenchymal injections of glutamate analogues into the diencephalon near the
      supraoptic (SON) and paraventricular nucleus (PVN) of the hypothalamus
      selectively spare magnocellular neuroendocrine cells. In this study we
      investigated for the first time the susceptibility of this neuronal population to
      ischemia. Temporary focal ischemia was produced using a three-vessel occlusion
      method involving unilateral middle cerebral artery and bilateral common carotid
      artery occlusion (MCAO/CCAO). Most of the 3-h ischemic period was maintained
      without anesthesia and reversed by microclip removal of the contralateral common
      carotid artery occlusion. In one subset of rats transcardial perfusion with India
      ink was used to estimate the degree of ischemia produced during MCAO/CCAO in the
      SON, lateral magnocellular nucleus of the PVN (PVL), caudoputamen (CP), and
      frontoparietal cortex (COR). Computer-assisted densitometry measurements of ink
      density indicated significant reductions in ink penetration in the territory of
      the occluded MCA within the SON (46%), PVL (45%), CP (53%), and COR (76%). In
      contrast, neither sham-operated rats nor rats subjected to occlusion of the MCA
      alone showed differences in ink optical densities between the sides ipsilateral
      and contralateral to MCAO. The other subset of rats were perfused 48-72 h after
      recovery and brain sections were examined for neurodegenerative changes. While
      the incidences of cerebral and caudoputamen infarction after MCAO/CCAO were 98.4
      and 52%, respectively, the histological features of the SON or PVL in ischemic
      rats were similar to those of control rats. Reduced susceptibility of
      magnocellular neuroendocrine cells to ischemia may be due to a number of
      mechanisms including neuronal resilience, neuroprotection by glia and
      vascular/perivascular cells, and access to perivascular cerebrospinal fluid.

PMID- 12504886
TI  - Spinal somatostatin SSTR2A receptors are preferentially up-regulated and involved
      in thermonociception but not mechanonociception.
AB  - The present study was undertaken to investigate the role of spinal somatostatin
      SSTR2A receptors in nociceptive processing. SSTR2A receptor-like immunoreactivity
      was found in a dense network in the spinal cord of normal rats. With Western blot
      analysis a major band of approximately 80-85 kDa was detected. Both
      immunohistochemistry and immunoblot analysis indicated a significant increase in
      SSTR2A receptor content in the spinal cord 6 h after noxious thermal stimulation
      that lasted for at least 24 h. However, there were no notable changes in SSTR2A
      receptor content 3, 6, 12, or 24 h after noxious mechanical stimulation. Effects
      of intrathecally administered polyclonal antiserum to SSTR2A receptor (anti
      SSTR2A) on thermal and mechanical pain thresholds were determined with behavioral
      tests. In normal rats, pretreatment with anti-SSTR2A (1 microl, intrathecal) did
      not affect paw withdrawal latency or pinch threshold. Hindpaw inflammation
      induced by complete Freund's adjuvant led to thermal and mechanical hyperalgesia
      as reflected by a robust decrease in paw withdrawal latency and pinch threshold.
      Significant attenuation of the thermal hyperalgesia was observed 3, 5, 7, 9, and
      24 h after pretreatment with anti-SSTR2A. This effect disappeared in another 24
      h. In contrast, pretreatment with anti-SSTR2A failed to exert any notable effect
      on adjuvant-induced mechanical hyperalgesia. The present findings provide the
      first evidence that SSTR2A receptors are responsible for thermal, but not
      mechanical, nociceptive transmission in the spinal cord. The results also suggest
      that somatostatin has an excitatory role in spinal nociceptive processing and
      that there are differential receptor responses to different types of noxious
      stimuli.

PMID- 12504887
TI  - Generation of neural progenitor cells from whole adult bone marrow.
AB  - The efficient and large-scale generation of neural progenitor cells for neural
      grafting in the treatment of neurological diseases has been a challenge. Here we
      describe the isolation and successful propagation of neural progenitor cells from
      adult rat bone marrow. Unfractionated bone marrow cultured in vitro with
      epidermal growth factor and basic fibroblast growth factor gave rise to cellular
      spheres which differentiated into neurons and glia. The cellular spheres
      expressed nestin, a neural stem cell marker as well as CD90, a marker of
      hematopoietic stem cells. This methodology addresses the ethical and tissue
      rejection problems associated with fetal neural stem cells and would circumvent
      the difficulty associated with generating neural progenitors from the adult
      brain. We demonstrate that bone marrow may offer a renewable autologous
      extracranial source of neural progenitor cells.

PMID- 12504888
TI  - Seizures and tissue injury induce telomerase in hippocampal microglial cells.
AB  - Telomerase is a reverse transcriptase that adds repeats of a six-base DNA
      sequence to chromosome ends and thereby prevents their shortening during
      successive cell divisions. Telomerase activity and expression of the catalytic
      subunit of telomerase (TERT) are high in brain cells during embryonic
      development, but are undetectable in the adult. We now report that telomerase
      activity and expression of TERT are induced in the hippocampus of adult mice
      after administration of the seizure-inducing excitotoxin kainate. Telomerase
      activity is present at 24 h and 7 days after kainate administration, but is no
      longer detectable at 4 weeks. Because the time course of telomerase induction was
      similar to the time course of microglial activation, we performed studies to
      determine whether microglia were the source of the telomerase activity.
      Examination of brain sections immunostained with a TERT antibody and an antibody
      against a microglia-specific antigen revealed that TERT was not detectable in the
      uninjured brain, and was present in microglia 24 h and 7 days after kainate
      administration. This is the first evidence that telomerase can be induced by
      brain injury and the first evidence that TERT can be expressed in microglia,
      suggesting roles for telomerase in microglial responses to brain injury.

PMID- 12504889
TI  - Dopamine receptor agonists mediate neuroprotection in malonate-induced striatal
      lesion in the rat.
AB  - Mitochondrial bioenergetic defects are involved in neurological disorders
      associated with neuronal damage in the striatum, such as Huntington's disease and
      cerebral ischemia. The striatal release of neurotransmitters, in particular
      dopamine, may contribute to the development of the neuronal damage. Recent
      studies have shown that dopamine agonists may exert neuroprotective effects via
      multiple mechanisms, including modulation of dopamine release from nigrostriatal
      dopaminergic terminals. In rats, intrastriatal injection of malonate, a
      reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces
      a lesion similar to that observed following focal ischemia or in Huntington's
      disease. In this study, we used the malonate model to explore the neuroprotective
      potential of dopamine agonists. Sprague-Dawley rats were injected systemically
      with increasing concentrations of D(1), D(2), or mixed D(1)/D(2) dopamine
      agonists prior to malonate intrastriatal insult. Administration of increasing
      doses of the D(2)-specific agonist quinpirole resulted in increased protection
      against malonate toxicity. Conversely, the D(1)-specific agonist SKF-38393, as
      well as the mixed D(1)/D(2) agonist apomorphine, conferred higher neuroprotection
      at lower than at higher concentrations. Our data suggest that malonate-induced
      striatal toxicity can be attenuated by systemic administration of dopamine
      agonists, with D(1) and D(2) agonists showing different profiles of efficacy.

PMID- 12504890
TI  - Increased beta-actin and tubulin polymerization in regrowing axons: relationship
      to the conditioning lesion effect.
AB  - Spinal motor neurons of Sprague-Dawley rats were examined to determine which of
      the neuronal isoforms of actin (beta or gamma) upregulate following axon injury.
      In situ hybridization studies showed greater beta-actin mRNA levels but no change
      in gamma-actin mRNA levels-suggesting that axon regrowth utilizes beta-actin. We
      radiolabeled the newly synthesized actin and tubulin that are subsequently
      transported in the axon to the site of an axotomizing injury. This allowed us to
      evaluate changes in polymerization as new cytoskeletal elements approach the
      injury site. Previous studies had shown that the rate of the most rapid
      subcomponent of actin and tubulin transport (called SCb) accelerates following
      axotomy (J. Jacob and I. McQuarrie, J. Neurobiol. 22: 570-583, 1991). This rate
      increase is associated with an increased proportion of SCb tubulin and actin in
      polymer (vs monomer) form (J. Jacob and I. McQuarrie, J. Neurosci, Res. 43: 412
      419, 1996). However, in that study newly synthesized proteins were radiolabeled
      at 7 days after axotomy-which is at the peak of increased protein synthesis. This
      time-course did not examine actin and tubulin that were already in transit in
      axons when the injury occurred. This actin and tubulin would enter the regrowing
      axons first. Here, we have radiolabeled newly synthesized proteins 3 days prior
      to axotomy. For beta-tubulin, the ratio of monomer to polymer was unaffected. For
      actin, the equilibrium shifted strongly toward polymerization. We conclude that
      the acceleration of axonal outgrowth seen after the second of two serial
      axotomies (the "conditioning lesion effect") is related to the ability of actin
      that is already in transit to polymerize in response to the first axotomy.

PMID- 12504891
TI  - Identification and characterization of a sucrose transporter isolated from the
      developing cotyledons of soybean.
AB  - Reduced carbon produced in mature leaves is distributed throughout plants in the
      form of sucrose. Sucrose transporter proteins (SUT) play a crucial role in
      transporting sucrose. We isolated a cDNA encoding a sucrose transporter, GmSUT1,
      which is expressed in the developing cotyledons of soybean (Glycine max).
      [14C]sucrose uptake assays demonstrate that GmSUT1 has a K(m) of 5.6mM and a
      V(max) of 5.8 nmol sucrose min(-1)(mg cells)(-1), which are similar to those of
      the low-affinity-high-capacity sucrose transporter family. GmSUT1 protein
      accumulates gradually during cotyledon development, correlating with increasing
      sucrose levels in the maturing cotyledons. Collectively, these data suggest that
      GmSUT1 plays an active role in the movement of sucrose into the developing seeds.

PMID- 12504892
TI  - Comparison of ligand polarization and enzyme activation in medium- and short
      chain acyl-coenzyme A dehydrogenase-novel analog complexes.
AB  - Spectroelectrochemical and off-resonance Raman indicate that substrate/product
      binding to medium-chain acyl-coenzyme A (CoA) dehydrogenase (pMCAD) results in
      ligand polarization and positive flavin potential shifts, which activate the
      enzyme for electron transfer. Bacterial short-chain acyl-CoA dehydrogenase
      (bSCAD) typically exhibits smaller potential shifts upon substrate/product
      binding that have not been linked to ligand polarization. To further investigate
      the roles of ligand binding and polarization in activation, several novel
      aromatic carboxyloyl-CoAs were designed. These analogs allowed for the first
      direct comparison of pMCAD and bSCAD mechanisms. The results indicate that pMCAD
      activation can occur without perceptible analog polarization. bSCAD data provide
      the first spectral evidence of ligand polarization. The potential alterations
      exhibited by ligand-bound bSCAD are smaller than those of pMCAD, while their
      directionality and magnitude suggest differing enzyme-analog interactions. Such
      data provide the first indication of variations in the activation mechanism of
      these enzymes, which were thought to be comparable in both structure and
      function.

PMID- 12504893
TI  - Progressive iron overload enhances chemically mediated tumor promotion in murine
      skin.
AB  - Iron overload has been shown to enhance chemically mediated cutaneous tumor
      promotion in animals. However, the majority of these animal studies have used
      high concentrations of iron before initiating tumor development. The current
      study was designed to evaluate the effect of small doses of iron on the promotion
      stage of chemically mediated cutaneous carcinogenesis. We found an increased
      tumor response in mice initiated with dimethylbenz(a)anthracene (DMBA) when iron
      at the dose levels of 0.5, 1.0, and 1.5mg/mouse was injected (intramuscularly)
      once a week into mice at the promotion stage of skin carcinogenesis, employing 12
      O-tetradecanoyl phorbol-13-acetate (TPA)/benzoyl peroxide (BPO) as tumor
      promoter. The appearance of first papilloma and the number of tumors/mouse were
      recorded weekly. When compared to the control (non-iron-treated) group, the iron
      treated groups showed an augmented incidence of tumors and number of
      tumors/mouse. In iron-treated mice, tumors appeared earlier than in the control
      group. TPA/BPO treatment resulted in a significant decrease in the activities of
      antioxidant enzymes and depletion in the level of epidermal reduced glutathione
      (GSH). TPA treatment in non-iron-treated mice resulted in approximately 20-40%
      decrease in GSH level and in the activities of antioxidant enzymes, whereas 1.5
      mg iron treatment along with TPA treatment resulted in about approximately 30-70%
      decrease in GSH level and in the activities of antioxidant enzymes. Similarly,
      treatment of iron along with BPO treatment resulted in a dose-dependent higher
      depletion of GSH and the antioxidant enzymes as compared to non-iron-treated
      animals treated with BPO. Further, TPA/BPO-mediated induction in ornithine
      decarboxylase activity and [3H]thymidine incorporation in cutaneous DNA was
      approx two- to threefold higher in mice treated with iron as compared to non-iron
      treated mice. Cutaneous lipid peroxidation and iron levels were also higher in
      mice treated with iron as compared to non-iron-treated mice. These data suggest
      that progressive iron overload can enhance the tumor promotion ability of TPA/BPO
      in DMBA-initiated murine skin.

PMID- 12504894
TI  - Methylglyoxal-bovine serum albumin stimulates tumor necrosis factor alpha
      secretion in RAW 264.7 cells through activation of mitogen-activating protein
      kinase, nuclear factor kappaB and intracellular reactive oxygen species
      formation.
AB  - Accumulating evidence suggests that the pathophysiology of diabetes is analogous
      to chronic inflammatory states. Circulating levels of inflammatory cytokines such
      as IL-6 and tumor necrosis factor alpha (TNFalpha) are increased in both type 1
      and type 2 diabetes. TNFalpha plays an important role in the pathogenesis of
      insulin resistance in type 2 diabetes. However, the reason for this increase
      remains unclear. Levels of the dicarbonyl methylglyoxal (MGO) are elevated in
      diabetic plasma and MGO-modified bovine serum albumin (MGO-BSA) can trigger
      cellular uptake of TNF. Therefore we tested the hypothesis that MGO-modified
      proteins may cause TNFalpha secretion in macrophage-like RAW 264.7 cells.
      Treatment of cells with MGO-BSA induced TNFalpha release in a dose-dependent
      manner. MGO-modified ribonuclease A and chicken egg ovalbumin had similar
      effects. Cotreatment of cells with antioxidant reagent N-acetylcysteine (NAC)
      inhibited MGO-BSA-induced TNFalpha secretion. MGO-BSA stimulated the simultaneous
      activation of p44/42 and p38 mitogen-activated protein kinase. PD98059, a
      selective MEK inhibitor, inhibited MGO-BSA-induced TNFalpha release as well as
      ERK phosphorylation. Pretreatment of cells with NAC also resulted in inhibition
      of MGO-BSA-induced ERK phosphorylation. MGO-BSA induced dose-dependent NFkappaB
      activation as shown by electrophoresis mobility shift assay. The MGO-BSA-induced
      NFkappaB activation was prevented in the presence of PD98059, NAC, and
      parthenolide, a selective inhibitor of NFkappaB. Furthermore, the NFkappaB
      inhibitor parthenolide suppressed MGO-BSA-induced TNFalpha secretion. Confocal
      microscopy using dichlorofluorescein to demonstrate intracellular reactive oxygen
      species (ROS) showed that MGO-BSA produced more ROS compared with native BSA. MGO
      BSA could also stimulate protein kinase C (PKC) translocation to the cell
      membrane, considered a key signaling pathway in diabetes. However, there was no
      evidence that PKC was involved in TNFalpha release based on inhibition by
      calphostin C and staurosporine. Our findings suggest that the presence of
      chronically elevated levels of MGO-modified bovine serum albumin may contribute
      to elevated levels of TNFalpha in diabetes.

PMID- 12504895
TI  - Mitochondrial and nucleocytoplasmic isoforms of O-linked GlcNAc transferase
      encoded by a single mammalian gene.
AB  - O-Linked N-acetylglucosamine (GlcNAc) transferase (OGT) mediates a novel
      hexosamine-dependent signal transduction pathway. Yet, little is known about the
      regulation of ogt gene expression in mammals. We report the sequence and
      characterization of the mouse ogt locus and provide a comparison with the human
      and rat ogt genes. The mammalian ogt genes are similar in structure and exhibit
      approximately 80% sequence identity. The mouse and human ogt genes contain two
      potential promoters producing four major transcripts. By analyzing 56 human cDNA
      clones and other existing expressed sequence tags, we found that at least three
      protein products differing at their amino terminus result from alternative
      splicing. We used OGT-specific antisera to demonstrate the presence of these
      isoforms in HeLa cells. The longest form is a nucleocytoplasmic OGT (ncOGT) with
      12 tetratricopeptide repeats (TPRs); a shorter form of OGT encodes a
      mitochondrially sequestered enzyme with 9 TPRs and an N-terminal mitochondrion
      targeting sequence (mOGT). An even shorter form of OGT (sOGT) contains only 2
      TPRs. The genomic organization of OGT appears to be highly conserved throughout
      metazoan evolution. These results provide the basis for a more detailed analysis
      of the significance and regulation of the nucleocytoplasmic and mitochondrial
      isoforms of OGT in mammals.

PMID- 12504896
TI  - Hormonal regulation of 25-hydroxyvitamin D3-1alpha-hydroxylase and 24-hydroxylase
      gene transcription in opossum kidney cells.
AB  - In the kidney, 25-hydroxyvitamin D(3) (25(OH)D) is converted to 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D) by the 25(OH)D(3)-1alpha-hydroxylase enzyme,
      which contains a terminal cytochrome P450 (CYP1alpha) (systematic name: CYP27B1).
      Likewise, the kidney also produces 24,25-dihydroxyvitamin D(3) and 1,24,25
      trihydroxyvitamin D(3) via a 24-hydroxylase whose terminal cytochrome P450 is
      CYP24. The purpose of this study was to characterize the transcriptional
      regulation of the CYP1alpha and CYP24 genes by parathyroid hormone (PTH) and
      1,25(OH)(2)D in the kidney. Promoter-reporter gene constructs were transfected
      into opossum kidney (OK) cells, a renal proximal tubular cell line with
      endogenous PTH and 1,25(OH)(2)D receptors. PTH and forskolin stimulated CYP1alpha
      promoter activity via a cAMP-dependent pathway acting through the phosphorylation
      of CREB (cAMP-dependent response element-binding protein). This stimulation did
      not require new protein synthesis but may be modulated by short-lived proteins.
      1,25(OH)(2)D modestly inhibited basal and forskolin-stimulated CYP1alpha promoter
      activity. The stimulation of CYP1alpha promoter activity by PTH and forskolin can
      account for the effect of these hormones on renal CYP1alpha mRNA levels. CYP24
      promoter activity in transfected cells was increased by both 1,25(OH)(2)D and
      PTH, but there was no interaction between the two. The modest effects of
      1,25(OH)(2)D and PTH on promoter activity and their lack of interaction do not
      account for the effects of these hormones on renal CYP24 mRNA levels. This
      suggests that there may be important posttranscriptional regulation of CYP24 mRNA
      in the kidney.

PMID- 12504897
TI  - Cytosine-block telomeric type DNA-binding activity of hnRNP proteins from human
      cell lines.
AB  - Following the observation of the presence in mammalian nuclear extracts of a DNA
      binding activity quite specific for the single-stranded C-rich telomeric motif,
      we have isolated from the K562 human cell line by affinity chromatography and
      identified by mass spectrometry a number of proteins able to bind to this
      sequence. All of them belong to different heterogeneous nuclear ribonucleoprotein
      subgroups (hnRNP). Whereas many of them, namely hnRNP K, two isoforms of hnRNP I,
      and the factor JKTBP, appear to bind to this sequence with limited specificity
      after isolation, an isoform of hnRNP D (alias AUF1) and particularly hnRNP E1
      (alias PCBP-1) show a remarkable specificity for the (CCCTAA)n repeated motif.
      Both have been obtained also as recombinant proteins expressed in Escherichia
      coli and have been shown to retain their binding specificity toward the C-block
      repeated sequence. In the light of the current knowledge about these proteins,
      their possible involvement in telomere functioning is discussed.

PMID- 12504898
TI  - Biotin sulfoxide reductase: Tryptophan 90 is required for efficient substrate
      utilization.
AB  - Rhodobacter sphaeroides f. sp. denitrificans biotin sulfoxide reductase (BSOR)
      catalyzes the reduction of d-biotin d-sulfoxide to biotin and contains the
      molybdopterin guanine dinucleotide (MGD) cofactor as its sole prosthetic group.
      Comparison of the primary sequences of BSOR and the closely related enzyme
      dimethyl sulfoxide reductase (DMSOR) indicated a number of conserved residues,
      including an active-site tryptophan residue (W90), which has been suggested to be
      involved in hydrogen bonding to the oxo group on the Mo(VI) center in BSOR. Site
      directed mutagenesis has been used to replace tryptophan 90 in BSOR with
      phenylalanine, tyrosine, and alanine residues to examine the role of this residue
      in catalysis. All three BSOR mutant proteins were purified to homogeneity and
      contained MGD. The mutant proteins retained very limited activity toward the
      oxidizing substrates tested, with W90F retaining the most activity (3.4% of wild
      type). All three W90 mutant proteins exhibited greatly reduced k(cat) values
      compared to that of the wild-type enzyme, which was accompanied by little change
      in K(mapp). In addition, the mutant proteins had perturbed visible absorption and
      circular dichroism spectra suggesting different oxidation states of the Mo
      center. Purified samples of wild-type BSOR did not exhibit electron paramagnetic
      resonance (EPR) signals indicating a Mo(VI) center. After redox-cycling,
      partially reduced samples of wild-type BSOR revealed a proton-split S=1/2 Mo(V)
      resonance (g(1,2,3)=1.999, 1.981, 1.967; A(1,2,3)=1.40, 1.00, 1.05 mT) analogous
      to that observed in DMSOR. In contrast, EPR studies of the purified W90 mutant
      proteins revealed distinct S=1/2 Mo(V) resonances that were resistant to both
      oxidation and reduction, indicating that the Mo was trapped in the intermediate
      Mo(V) oxidation state. These results strongly suggest that W90 in BSOR plays a
      critical role in catalysis by serving as a hydrogen bond donor to the oxo group
      on the Mo(VI) center.

PMID- 12504899
TI  - Inhibition by phenylglyoxal of nitrate transport in Paracoccus denitrificans: a
      comparison with the effect of a protonophorous uncoupler.
AB  - The amino acid modifier phenylglyoxal (PG) gradually inactivated the methyl
      viologen-coupled nitrate reductase activity of the anoxically grown whole cells
      of Paracoccus denitrificans. A double log plot of the pseudo-first-order
      inactivation rate constant versus PG concentration was linear with a mean slope
      of 1.4 (0.1M sodium phosphate) or 0.87 (0.1M sodium borate). Phenylglyoxalation
      of cells lowered the limiting velocity (V), while hardly affecting the apparent
      half-saturation concentration (K(m)) of nitrate. Nitrate afforded no protection
      against inactivation. The inhibition by PG could be removed by the detergent
      Triton X-100 or by the lipid-soluble tetraphenylphosphonium countercation,
      suggesting that PG exerts its effect at the level of nitrate transport. Based on
      studies with membrane potential- and pH-sensitive fluorescent probes, the
      inhibition was shown not to be due to changes in the electrochemical gradient of
      hydrogen ions. Both K(m) and V values for nitrate uptake increased in a
      hyperbolic fashion in response to exogenously added nitrite. Nitrite promoted a
      bypass of the inhibition caused by low concentrations of the proton-conducting
      agent carbonyl cyanide m-chlorophenylhydrazone (CCCP), but was almost ineffective
      in the case of the PG block. These results are rationalized in terms of two
      nitrate import pathways that are comparably inhibited by PG and differ in their
      sensitivities to CCCP. A simplified kinetic model for phenylglyoxalation is
      proposed to account for the observed nonintegral reaction orders.

PMID- 12504900
TI  - Rational design of tropoelastin peptide-based inhibitors of metalloproteinases.
AB  - Abnormal production of matrix metalloproteinases (MMPs) has been observed in a
      variety of diseases, such as emphysema, atherosclerosis, and cancer metastasis.
      Destruction of connective tissue ensues and elastin is often a key target. Three
      of the main elastolytic MMPs are the gelatinases MMP-2 and MMP-9 and the
      metalloelastase MMP-12. To investigate the possibility of using peptides to
      inhibit the elastolytic activity of these enzymes, we mapped the sites within
      tropoelastin recognized by MMP-9 and MMP-12. Peptides that correspond to regions
      overlapping these sites were then tested for their ability to inhibit these MMPs.
      These included an unmodified peptide directed against MMP-9 (peptide PP),
      cysteine-containing peptides that mimicked either the MMP-9 (peptide NCP) or the
      MMP-12 (peptide lin24) cleavage sites in tropoelastin and their cyclized forms
      (CP and cyc24, respectively), and a peptide containing a zinc-chelating
      hydroxamate group directed against MMP-9 (HP). The presence of a free sulfhydryl
      or hydroxamate group capable of chelating the zinc ion in the active site of the
      MMPs was generally found to increase the inhibitory activity of the peptides. The
      specificity of the inhibitors varied, with some of the inhibitors showing
      activity against all of the MMPs examined. None of the inhibitors had any
      significant effect on the activity of the unrelated serine protease, plasmin.
      K(i) values for the inhibitors were in the micromolar range. Our results suggest
      ways of developing other MMP inhibitors based on substrate recognition sites that
      may provide greater levels of inhibition.

PMID- 12504901
TI  - N-Terminal modifications of the 19S regulatory particle subunits of the yeast
      proteasome.
AB  - The yeast (Saccharomyces cerevisiae) contains three N-acetyltransferases, NatA,
      NatB, and NatC, each of which acetylates proteins with different N-terminal
      regions. The 19S regulatory particle of the yeast 26S proteasome consists of 17
      subunits, 12 of which are N-terminally modified. By using nat1, nat3, and mak3
      deletion mutants, we found that 8 subunits, Rpt4, Rpt5, Rpt6, Rpn2, Rpn3, Rpn5,
      Rpn6, and Rpn8, were NatA substrates, and that 2 subunits, Rpt3 and Rpn11, were
      NatB substrates. Mass spectrometric analysis revealed that the initiator Met of
      Rpt2 precursor polypeptide was processed and a part of the mature Rpt2 was N
      myristoylated. The crude extracts from the normal strain and the nat1 deletion
      mutant were similar in chymotrypsin-like activity in the presence of ATP in vitro
      and in the accumulation level of the 26S proteasome. These characteristics were
      different from those of the 20S proteasome: the chymotrypsin-like activity and
      accumulation level of 20S proteasome were appreciably higher from the nat1
      deletion mutant than from the normal strain.

PMID- 12504902
TI  - Oxidative damage to ferritin by 5-aminolevulinic acid.
AB  - 5-Aminolevulinic acid (ALA), a heme precursor overproduced in various porphyric
      disorders, has been implicated in iron-mediated oxidative damage to biomolecules
      and cell structures. From previous observations of ferritin iron release by ALA,
      we investigated the ability of ALA to cause oxidative damage to ferritin
      apoprotein. Incubation of horse spleen ferritin (HoSF) with ALA caused
      alterations in the ferritin circular dichroism spectrum (loss of a alpha-helix
      content) and altered electrophoretic behavior. Incubation of human liver, spleen,
      and heart ferritins with ALA substantially decreased antibody recognition (51,
      60, and 28% for liver, spleen, and heart, respectively). Incubation of
      apoferritin with 1-10mM ALA produced dose-dependent decreases in tryptophan
      fluorescence (11-35% after 5h), and a partial depletion of protein thiols (18%
      after 24h) despite substantial removal of catalytic iron. The loss of tryptophan
      fluorescence was inhibited 35% by 50mM mannitol, suggesting participation of
      hydroxyl radicals. The damage to apoferritin had no effect on ferroxidase
      activity, but produced a 61% decrease in iron uptake ability. The results suggest
      a local autocatalytic interaction among ALA, ferritin, and oxygen, catalyzed by
      endogenous iron and phosphate, that causes site-specific damage to the ferritin
      protein and impaired iron sequestration. These data together with previous
      findings that ALA overload causes iron mobilization in brain and liver of rats
      may help explain organ-specific toxicities and carcinogenicity of ALA in
      experimental animals and patients with porphyria.

PMID- 12504903
TI  - Interaction of wheat high-mobility-group proteins with four-way-junction DNA and
      characterization of the structure and expression of HMGA gene.
AB  - Plant high-mobility-group (HMG) chromosomal proteins are the most abundant and
      ubiquitous nonhistone proteins found in the nuclei of higher eukaryotes. There
      are only two families of HMG proteins, namely, HMGA and HMGB in plants. The cDNA
      encoding wheat HMGa protein was isolated and characterized. Wheat HMGA cDNA
      encodes a protein of 189 amino acid residues. At its N terminus, there is a
      histone H1-like structure, which is a common feature of plant HMGA proteins,
      followed by four AT-hook motifs. Polymerase chain reaction results show that the
      gene contains a single intron of 134 bp. All four AT-hook motifs are encoded by
      the second exon. Northern blot results show that the expression of HMGA gene is
      much higher in organs undergoing active cell proliferation. Gel retardation
      analysis show that wheat HMGa, b, c and histone H1 bind to four-way-junction DNA
      with high binding affinity, but affinity is dramatically reduced with increasing
      Mg(2+) and Na(+) ion concentration. Competition binding studies show that
      proteins share overlapping binding sites on four-way-junction DNA. HMGd does not
      bind to four-way-junction DNA.

PMID- 12504904
TI  - Inhibition of the cysteine proteinases cathepsins K and L by the serpin headpin
      (SERPINB13): a kinetic analysis.
AB  - Headpin (SERPINB13) is a novel member of the serine proteinase inhibitor (Serpin)
      gene family that was originally cloned from a keratinocyte cDNA library. Western
      blot analysis using a headpin-specific antiserum recognized a protein with the
      predicted M(r) of 44kDa in lysates derived from a transformed keratinocyte cell
      line known to express headpin mRNA. Similarity of the reactive-site loop (RSL)
      domain of headpin, notably at the P1-P1(') residues, with other serpins that
      inhibit cysteine and serine proteinases suggests that headpin may inhibit similar
      proteinases. This study demonstrates that recombinant headpin indeed inhibits
      cathepsins K and L, but not chymotrypsin, elastase, trypsin, subtilisin A,
      urokinase-type plasminogen activator, plasmin, or thrombin. The second-order rate
      constants (k(a)) for the inhibitory reactions of rHeadpin with cathepsins K and L
      were 5.1+/-0.6x10(4) and 4.1+/-0.8x10(4)M(-1)s(-1), respectively. Headpin formed
      SDS-stable complexes with cathepsins K and L, a characteristic property of
      inhibitory serpins. Interactions of the RSL domain of headpin with cathepsins K
      and L were indicated by cleavage of headpin near the predicted P1-P1(') residues
      by these proteinases. These results demonstrate that the serpin headpin possesses
      specificity for inhibiting lysosomal cysteine proteinases.

PMID- 12504905
TI  - Arginine of retinoic acid receptor beta which coordinates with the carboxyl group
      of retinoic acid functions independent of the amino acid residues responsible for
      retinoic acid receptor subtype ligand specificity.
AB  - The biological actions of retinoic acid (RA) are mediated by retinoic acid
      receptors (RARalpha, RARbeta, and RARgamma) and retinoid X receptors (RXRalpha,
      RXRbeta, and RXRgamma). Consistent with the X-ray crystal structures of RARalpha
      and RARgamma, site-directed mutagenesis studies have demonstrated the importance
      of a conserved Arg residue (alphaArg(276), betaArg(269), and gammaArg(278)) for
      coordination with the carboxyl group of RA. However, mutation of Arg(269) to Ala
      in RARbeta causes only a 3- to 6-fold increase in the K(d) for RA and EC(50) in
      RA-dependent transcriptional transactivation assays while the homologous mutation
      in either RARalpha or RARgamma causes a 110-fold and a 45-fold increase in EC(50)
      value, respectively. To further investigate the nature of this difference, we
      prepared mutant RARs to determine the effect of conversion of betaR269A to a
      mutant which mimics either RARalpha ligand selectivity (betaA225S/R269A) or
      RARgamma ligand selectivity (betaI263M/R269A/V338A). Our results demonstrate that
      in RARbeta mutants that acquire either RARalpha or RARgamma ligand specificity
      the Arg(269) position responsible for coordination with the carboxyl group of
      retinoids continued to function like that of RARbeta. Furthermore, three mutant
      receptors (betaA225S/R269A, betaA225S/F279, and alphaF286A) were found to have a
      greater than wild-type affinity for the RARalpha-selective ligand Am580. Finally,
      a homology-based computer model of the ligand binding domain (LBD) of RARbeta and
      the X-ray crystal structures of the LBD of both RARalpha and RARgamma are used to
      describe potential mechanisms responsible for the increased affinity of some
      mutants for Am580 and for the difference in the effect of mutation of Arg(269) in
      RARbeta compared to its homologous Arg in RARalpha and RARgamma.

PMID- 12504906
TI  - Probing sesquiterpene hydroxylase activities in a coupled assay with terpene
      synthases.
AB  - 5-epi-Aristolochene dihydroxylase (EAH) catalyzes unique stereo- and
      regiospecific hydroxylations of a bicyclic sesquiterpene hydrocarbon to generate
      capsidiol. To define functional and mechanistic features of the EAH enzyme, the
      utility of a coupled assay using readily available sesquiterpene synthases and
      microsomes from yeast overexpressing the EAH enzyme was determined. Capsidiol and
      deoxycapsidiol biosyntheses were readily measured in coupled assays consisting of
      5-epi-aristolochene synthase and EAH as determined by the incorporation of
      radiolabeled farnesyl diphosphate into thin-layer chromatography-isolated
      products and verified by gas chromatography-mass spectrometry analysis. The
      assays were dependent on the amounts of synthase and hydroxylase protein added,
      the incubation times, and the presence of nicotinamide adenine dinucleotide
      phosphate. The utility of this coupled assay was extended by examining the
      relative efficiency of the EAH enzyme to catalyze hydroxylations of different
      sesquiterpene skeletons generated by other terpene synthases.

PMID- 12504907
TI  - Evidence for heterogeneous forms of the snake venom metalloproteinase jararhagin:
      a factor contributing to snake venom variability.
AB  - The reprolysin subfamily of metalloproteinases includes snake venom
      metalloproteinases (SVMP) and mammalian disintegrin/metalloproteinase. These
      proteins are synthesized as zymogens and undergo proteolytic processing resulting
      in a variety of multifunctional proteins. Jararhagin is a P-III SVMP isolated
      from the venom of Bothrops jararaca. In crude venom, two forms of jararhagin are
      typically found, full-length jararhagin and jararhagin-C, a proteolytically
      processed form of jararhagin that is composed of the disintegrin-like and
      cysteine-rich domains of jararhagin. To better understand the structural and
      mechanistic bases for these forms of jararhagin in the venom of B. jararaca and
      the source of venom complexity in general, we have examined the jararhagin forms
      isolated from venom and the autolysis of isolated jararhagin under the conditions
      of varying pH, calcium ion concentration, and reducing agents. From our results,
      jararhagin isolated from venom appears as two forms: a predominant form that is
      stable to in vitro autolysis and a minor form that is susceptible to autolysis
      under a variety of conditions including alkaline pH, low calcium ion
      concentrations, or reducing agent. The autolysis site for production of
      jararhagin-C from isolated jararhagin was different from that observed for
      jararhagin-C as isolated from crude venom. Taken together, these data lead us to
      the conclusion that during the biosynthesis of jararhagin in the venom gland at
      least three forms are present: one form which is rapidly processed to give rise
      to jararhagin-C, one form which is resistant to processing in the venom and
      autolysis in vitro, and one minor form which is susceptible to autolysis under
      conditions that promote destabilization of its structure. The presence of these
      different forms of jararhagin contributes to greater structural and functional
      complexity of the venom and may be a common feature among all snake venoms. The
      biological and biochemical features in the venom gland responsible for these
      jararhagin isoforms are currently under investigation.

PMID- 12504908
TI  - Latent phenoloxidase activity and N-terminal amino acid sequence of hemocyanin
      from Bathynomus giganteus, a primitive crustacean.
AB  - N-terminal amino acid sequences for the two hemocyanin subunits from the deep-sea
      crustacean Bathynomus giganteus have been determined by Edman degradation,
      providing the first sequence information for a hemocyanin from an isopod. In
      addition, purified hemocyanin from B. giganteus exhibited phenoloxidase activity
      in the presence of sodium dodecyl sulfate. Although a natural activator has not
      yet been identified, a preliminary study of the enzyme indicated a K(m) of 5mM
      for dopamine and an initial rate of 0.1 micromol per min per mg protein, values
      consistent with a significant role for this enzyme in the innate immune system of
      B. giganteus. Moreover, after separation of hemolymph by alkaline polyacrylamide
      gel electrophoresis, the only detectable phenoloxidase activity coincided with
      the two hemocyanin subunits. The hemocyanin of this primitive crustacean may
      fulfill dual functions, both as oxygen carrier and as the phenoloxidase crucial
      for host defense.

PMID- 12504909
TI  - Myosin II is important for maintaining regulated secretion and asymmetric
      localization of chitinase 1 in the budding yeast Saccharomyces cerevisiae.

PMID- 12504910
TI  - Potassium channels as anti-epileptic drug targets.
AB  - It is estimated that up to 30% of epilepsy patients are poorly treated with
      available anti-epileptic drugs (AEDs). Thus, there is a medical need for new AEDs
      with novel mechanisms of action to serve as alternate or adjunct therapy for the
      treatment of drug-resistant or refractory epilepsy. One potential anti-epileptic
      mechanism that has not yet been exploited is K(+) channel opening. Considerable
      genetic, molecular, physiological and pharmacological evidence now exists to
      support a role for K(+) channels such as KCNQ2/Q3, Kv1.1, KATP and GIRK2 in the
      control of neuronal excitability and epileptogenesis. Evidence supporting these
      K(+) channels as novel AED targets will be reviewed in the following article.

PMID- 12504911
TI  - Type I and II metabotropic glutamate receptors modulate periaqueductal grey
      glycine release: interaction between mGlu2/3 and A1 adenosine receptors.
AB  - In this study we investigated the effects of type I and II mGlu receptors ligands
      in glycine extracellular concentrations at the periaqueductal gray (PAG) level by
      using in vivo microdialysis, in conscious rats. An agonist of type I mGlu
      receptors, (S)-3,5-DHPG (1 and 5 mM), but not a selective agonist for mGlu5
      receptors, CHPG (3 and 5 mM), was noticed to increase the dialysate glycine
      levels in a concentration-dependent manner (60+/-15% and 136+/-13%,
      respectively). CPCCOEt (1mM), a selective mGlu1 receptor antagonist, perfused in
      combination with (S)-3,5-DHPG, counteracted the effect induced by (S)-3,5-DHPG,
      but did not change per se the extracellular PAG glycine values, even at the
      highest dosage used (2 mM). MPEP (1 and 2 mM), a selective antagonist of mGlu5
      receptor, did not modify extracellular glycine level. An agonist of type II mGlu
      receptors, 2R,4R-APDC (25 and 50 microM), decreased the dialysate glycine in a
      concentration-dependent manner (-26+/-4% and -54+/-6%, respectively). The 2R,4R
      APDC-induced decrease in extracellular glycine was prevented by EGlu (0.5 mM), a
      selective type II mGlu receptors antagonist. EGlu (0.5 and 1 mM), per se, led to
      a significant decrease (-56+/-7% and -57+/-2%, respectively) in extracellular PAG
      glycine too. This effect was prevented by DPCPX (100 microM), a selective
      antagonist for A1 adenosine receptors, but was not affected by CPA (1 mM), a
      selective A1 adenosine receptors agonist. Intra-PAG perfusion of CPA (0.1-1 mM)
      decreased the extracellular PAG glycine values (-47+/-13%) with 1 mM
      concentration. The CPA-induced effect was prevented by DPCPX (100 microM), and
      resulted to be additive with the 2R,4R-APDC-induced decrease in glycine values.
      DPCPX (1 mM) increased per se extracellular glycine (48+/-7%) at the highest dose
      used. Dipyridamole (100 microM), an inhibitor of both adenosine reuptake and
      phosphodiesterases, decreased extracellular glycine (-28+/-7%). Extracellular
      concentrations of glutamine never changed throughout this study. These data show
      opposing effects of type I and II mGlu receptors in the regulation of PAG glycine
      values. Moreover, functional interaction between type II mGlu and adenosine A1
      receptors, which possibly operate through a common transductional pathway, may be
      relevant in the physiological control of glycine release in awake, freely moving
      rats at the periaqueductal gray matter.

PMID- 12504912
TI  - Reduction of elevated arterial blood pressure in obese Zucker rats by inhibition
      of ganglionic long-term potentiation.
AB  - Sustained enhancement of the basal tone of ganglionic transmission is expected to
      result in an enduring increase in peripheral resistance that would lead to
      elevated blood pressure. Long-term potentiation of sympathetic ganglia is an
      activity-dependent long-lasting increase in strength of ganglionic transmission.
      Therefore, ganglionic long-term potentiation might be involved in the
      manifestation of neurogenic forms of hypertension. Expression of sympathetic
      ganglionic long-term potentiation is dependent on activation of 5-HT(3) receptor.
      We examined the possibility that elevated blood pressure in obese Zucker rat,
      which is reported to be stress-prone, might be partly due to a neurogenic factor
      resulting from expression of ganglionic long-term potentiation. Chronic treatment
      with the 5-HT(3) receptor antagonist ondansetron (0.5 mg/kg/day) caused a
      significant decrease in blood pressure of the obese Zucker rats without affecting
      that of normotensive lean Zucker rats. Electropysiological procedures to test for
      long-term potentiation in isolated ganglia suggest that ganglionic long-term
      potentiation has been previously expressed in vivo in ganglia from obese Zucker
      rat but not in those from the normotensive lean Zucker rats. The results indicate
      that expression of ganglionic long-term potentiation in sympathetic ganglia may
      be responsible for neurogenic increase in blood pressure, which contributes to
      the moderate hypertension often seen in the obese Zucker rats.

PMID- 12504913
TI  - Gabapentin-- actions on adult superficial dorsal horn neurons.
AB  - Despite identification of GABA(B) receptors with gb1a-gb2 composition and the
      alpha2delta calcium channel subunit as putative molecular targets for gabapentin
      (GBP), its cellular mechanism of action has remained elusive. Therefore, we have
      used an in vitro spinal cord slice preparation to study the effects of GBP on
      lamina II neurons. The frequency and amplitude of spontaneous EPSCs and IPSCs
      were unaffected by GBP, suggesting presynaptic neurotransmitter release is not
      regulated. Direct modulation of postsynaptic membrane excitability is also
      unlikely since the level of holding current required to maintain neurons at -70,
      0 and +45 mV was unaffected by GBP. Effects on excitatory and inhibitory synaptic
      transmission were variable across the population. Primary afferent-evoked fast
      glutamatergic EPSCs were unaffected by GBP, while evoked NMDA receptor-mediated
      EPSCs and IPSCs were variably affected. In contrast, GBP enhanced responses to
      bath applied NMDA in 71% of neurons. Thus, in adult rat dorsal horn, synaptic and
      extrasynaptic NMDA receptors may be differentially regulated by GBP perhaps due
      to differences in subunit composition.

PMID- 12504914
TI  - Low-affinity kainate receptor-mediated events reduce the protective activity of
      phenobarbital and diphenylhydantoin against maximal electroshock in mice.
AB  - (2S,2R)-4-Methylglutamic acid (SYM 2081), a potent selective agonist of GluR5 and
      GluR6 kainate receptor subtypes, applied at the dose of 15.5 mg/kg, equal to its
      CD(16) value (i.e., a dose required to induce convulsions in 16% of mice),
      significantly decreased the electroconvulsive threshold from 7.0 to 5.8 mA. When
      administered at the dose of 11.5 mg/kg, equal to 75% of its CD(16), it markedly
      attenuated the protective activity of phenobarbital and diphenylhydantoin, but
      not that of valproate, carbamazepine, or diazepam against maximal electroshock
      induced seizures in mice. The respective ED(50) values were increased from 18.5
      to 23.8 mg/kg for phenobarbital, and from 11.7 to 14.7 mg/kg for
      diphenylhydantoin. Since the free plasma levels of both antiepileptic drugs were
      not influenced by SYM 2081, the pharmacokinetic interaction does not seem to be
      involved in the observed results. In conclusion, low-affinity kainate receptor
      mediated events might be a factor reducing the protective efficacy of some
      antiepileptic drugs. Furthermore, the activation of GluR5 and GluR6 kainate
      receptor subtypes by endogenous glutamate during seizures may be associated with
      the drug-resistance phenomenon.

PMID- 12504915
TI  - Dual cooperative allosteric modulation of binding to ionotropic glycine
      receptors.
AB  - Glycine receptors (GlyRs) were studied via [(3)H]strychnine binding to
      synaptosomal membranes of rat spinal cord. A ternary allosteric model was applied
      for the effects of tropeines, alcohols, minaxolone, nitrendipine, Zn(2+),
      muscarinic and serotonin receptor ligands. It enabled us to determine the
      dissociation constants of the allosteric agents (K(A)) and their cooperativity
      factors affecting the dissociation constants of [(3)H]strychnine (alphaK(S)) and
      glycine (betaK(L)). Cooperativity with [(3)H]strychnine ranged from strong
      negative for tropeines to weak positive for nitrendipine. Displacement curves of
      glycine were examined in the presence of allosteric agents. Positive
      cooperativities with glycine were found for submicromolar concentrations of
      tropisetron, bemesetron, zatosetron and nitrendipine; for tubocurarine, propofol,
      butanol, minaxolone, cocaine and 10 microM Zn(2+). Micromolar concentrations of
      tropisetron and nitrendipine showed weaker cooperativities. Other allosteric
      agents and 1 mM Zn(2+) displayed negative cooperativity with glycine. Binding
      parameters K(A) and beta correlate excellently with the activities of the
      allosteric agents on GlyR-ionophores. Combined inhibitory effects of the
      allosteric agents suggest that there are different subgroups (tropeines, alcohols
      and dihydropyridines) binding to distinct sites on GlyRs exerting cooperativity
      with glycine via a common mechanism. This is the first quantitative analysis of
      allosteric binding interactions for GlyRs.

PMID- 12504916
TI  - Central serotonin4 receptors selectively regulate the impulse-dependent
      exocytosis of dopamine in the rat striatum: in vivo studies with morphine,
      amphetamine and cocaine.
AB  - In vivo microdialysis and single-cell extracellular recordings were used to
      assess the involvement of serotonin(4) (5-HT(4)) receptors in the effects induced
      by morphine, amphetamine and cocaine on nigrostriatal and mesoaccumbal
      dopaminergic (DA) pathway activity. The increase in striatal DA release induced
      by morphine (2.5 mg/kg, s.c.) was significantly reduced by the selective 5-HT(4)
      antagonists GR 125487 (0.1 and 1 mg/kg, i.p.) or SB 204070 (1 mg/kg, i.p.), and
      potentiated by the 5-HT(4) agonist prucalopride (5 mg/kg, i.p.). Neither of these
      compounds affected morphine-stimulated DA release in the nucleus accumbens. In
      both regions, amphetamine (2 mg/kg, i.p.) and cocaine (15 mg/kg, i.p.) induced DA
      release was affected neither by GR 125487 nor by prucalopride. None of the 5-HT
      agents used modified basal DA release in either brain region. Finally, GR 125487
      (445 microg/kg, i.v.), whilst not affecting basal firing of DA neurons within
      either the substantia nigra pars compacta nor the ventral tegmental area,
      significantly reduced morphine (0.1-10 mg/kg, i.v.) stimulated firing of
      nigrostriatal DA neurons only. These results confirm that 5-HT(4) receptors exert
      a state-dependent facilitatory control restricted to the nigrostriatal DA
      pathway, and indicate that 5-HT(4) receptors selectively modulate DA exocytosis
      associated with increased DA neuron firing rate.

PMID- 12504917
TI  - Pharmacological properties of the anti-Parkinson drug rasagiline; modification of
      endogenous brain amines, reserpine reversal, serotonergic and dopaminergic
      behaviours.
AB  - Rasagiline [N-propargyl-1R(+)-aminoindan; TVP1012] is a potent irreversible
      monoamine oxidase (MAO) inhibitor with selectivity for type B of the enzyme,
      which is being developed for treatment of Parkinson's disease. In this study we
      examined effects of rasagiline on CNS monoamine levels, modification of
      behavioural response to L-tryptophan, fluoxetine and L-DOPA, and reversal of
      reserpine syndrome. Reserpine-induced ptosis was reversed by rasagiline at doses
      above 2 mg x kg(-1) i.p., which inhibit MAO-A as well as MAO-B, but not at MAO-B
      selective doses. However, combination of rasagiline (10 mg x kg(-1) i.p.) with L
      DOPA or L-tryptophan (50 mg x kg(-1) i.p.), or rasagiline (10 mg x kg(-1) p.o.)
      with fluoxetine (10 mg x kg(-1) p.o.), did not induce the behavioural
      hyperactivity syndrome which is seen following inhibition of both MAO-A and MAO-B
      by tranylcypromine together with the monoamine precursors. Following oral
      administration, levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and
      dopamine (DA) were unaffected in hippocampus and striatum after single doses of
      rasagiline up to 2 mg x kg(-1). Following chronic oral administration (21 days,
      one dose daily), levels of NA, 5-HT and DA in hippocampus and striatum were
      unaffected by rasagiline at doses up to 1 mg x kg(-1). Rasagiline does not modify
      CNS monoamine tissue levels or monoamine-induced behavioural syndromes at doses
      which selectively inhibit MAO-B but not MAO-A.

PMID- 12504918
TI  - Gender and gonadal status modulation of dorsal raphe nucleus serotonergic
      neurons. Part I: effects of gender and pregnancy.
AB  - Gender differences in susceptibility to affective disorders are well documented.
      The ovarian steroids, estrogen (E) and progesterone (P), may modulate the
      function of the serotonergic (5-HT) system, implicated in the etiology and
      treatment of affective disorders. We tested the hypothesis that ovarian steroid
      modulation of 5-HT function could result in a modification of the 5-HT neuronal
      firing activity. Extracellular unitary recordings of dorsal raphe nucleus 5-HT
      neurons were obtained in male rats and in female rats during natural E and P
      fluctuations. The average firing activity of 5-HT neurons was significantly
      higher in males (41%) than in freely cycling (CF) and in ovariectomized (OVX)
      females. During pregnancy, it increased gradually and by up to 136% on
      gestational day 17, then declined before parturition. In the postpartum period
      (PP), the firing rate decreased markedly compared to P17 but remained 63% higher
      than in CF. During pregnancy, the firing rate variations were closely correlated
      with P plasmatic levels. Finally no modification of the basal firing activity of
      locus coeruleus noradrenergic neurons was found in any group tested. Our results
      thus reveal a gender and pregnancy-dependent modulation of 5-HT firing rate that
      would impact 5-HT-mediated neurotransmission.

PMID- 12504919
TI  - Gender and gonadal status modulation of dorsal raphe nucleus serotonergic
      neurons. Part II. Regulatory mechanisms.
AB  - In the companion paper, we showed that the spontaneous firing activity of DRN 5
      HT neurons is significantly higher in male (M) than in freely cycling female (CF)
      rats. Moreover, during pregnancy, it increased in parallel to circulating levels
      of progesterone, peaking at day 17 of pregnancy (P17). In this second part, we
      assessed the role of three regulatory mechanisms potentially involved in these
      modifications of the 5-HT neurons firing activity. During pregnancy, the ED(50)
      for the response to LSD was decreased by about 70%, indicating a partial
      desensitization of 5-HT(1A) autoreceptors, which is consistent with the 5-HT
      neurons higher firing activity. The GABAergic tonic inhibition of 5-HT neurons
      was assessed using the responses to GABA, bicuculline and isoniazid. Together,
      they indicate a lower GABAergic tonic inhibition in males and P17 as compared to
      CF, which is in agreement with their greater 5-HT neurons firing rate. Finally,
      the efficacy of the long feedback loop, involving postsynaptic 5-HT(1A)
      receptors, did not seem affected by gender, ovariectomy or pregnancy since the
      response to systemic 8-OH-DPAT was similar. These results constitute strong
      evidence of mechanisms by which gender and hormonal fluctuations can modulate the
      5-HT neurons function and influence vulnerability to mood disorders.

PMID- 12504920
TI  - Modulatory effects of norepinephrine, acting on alpha 1 receptors in the central
      nucleus of the amygdala, on behavioral and neuroendocrine responses to acute
      immobilization stress.
AB  - The central nucleus of the amygdala (CeA) is a component of the limbic fear
      anxiety circuit, and has also been implicated in regulation of the hypothalamic
      pituitary-adrenal (HPA) stress axis. The CeA receives dense noradrenergic
      innervation, and is rich in expression of alpha(1)-adrenergic receptors. We
      hypothesized that norepinephrine (NE), acting on alpha(1) receptors in CeA, may
      modulate stress-induced anxiety-like behavioral responses and HPA activation. To
      investigate the role of alpha(1) adrenergic receptors in CeA on stress-induced
      behavioral reactivity, the alpha(1) antagonist benoxathian was microinjected
      bilaterally into CeA of male Sprague-Dawley rats, and anxiety-like behavioral
      responses to acute immobilization stress were measured on the Social Interaction
      (SI) test and on the Elevated Plus-maze (EPMZ). Benoxathian dose dependently
      blocked the reduction in SI time induced by immobilization stress, whereas beta
      receptor antagonists had no effect, consistent with an absence of beta-receptors
      in CeA. By contrast, in separate experiments, benoxathian had no effect on stress
      induced reduction in open-arm exploratory behavior on the EPMZ, nor on stress
      induced plasma ACTH secretion. These results confirm that the SI test and EPMZ
      measure different aspects of behavioral stress reactivity that can be modulated
      independently, and likewise, that noradrenergic modulation of behavioral stress
      reactivity can occur independently of modulation of the HPA axis.

PMID- 12504921
TI  - Regulation of cAMP phosphodiesterase mRNAs expression in rat brain by acute and
      chronic fluoxetine treatment. An in situ hybridization study.
AB  - Changes in brain cyclic AMP (cAMP) have been suggested to underlie the clinical
      action of antidepressant treatments. Also, a regionally-selective regulation of
      cAMP-specific phosphodiesterases (PDEs) has been demonstrated for some
      antidepressants. To further investigate the effects of antidepressant treatments
      on PDEs, we examined the expression of different cAMP-specific PDEs in the brain
      of rats treated (1 and 14 days) with fluoxetine 3 mg/kg day. The mRNAs coding for
      PDE4A, PDE4B, PDE4D, and the five known PDE4D splice variants were analyzed by in
      situ hybridization on 45 brain structures of acute and chronic fluoxetine-treated
      rats. We also examined the binding sites for the putative antidepressant drug
      [(3)H]rolipram, a PDE4-selective inhibitor. In some brain areas single fluoxetine
      administration increased the density of the mRNA of all PDE4 isozymes, except
      PDE4D and PDE4D5. Chronic fluoxetine treatment increased PDE4A mRNA levels and
      decreased those for PDE4B, PDE4D and PDE4D1 mRNAs in some brain regions. The
      study was complemented with the analysis of the expression of the transcripts of
      BDNF. Chronic fluoxetine treatment down-regulated the expression of BDNF. These
      results show that the expression of PDE4 isozymes is modulated by a clinically
      relevant fluoxetine dose. The significance of these changes in PDE4 expression to
      the antidepressant effect of fluoxetine is discussed.

PMID- 12504922
TI  - Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium
      valproate and lithium.
AB  - This study tested if sodium valproate or lithium, two agents used to treat
      bipolar mood disorder, altered the regulatory phosphorylations of Akt or glycogen
      synthase kinase-3beta (GSK3beta) in human neuroblastoma SH-SY5Y cells. Treatment
      with sodium valproate caused a gradual but relatively large increase in the
      activation-associated phosphorylation of Akt on Ser-473, and a similarly gradual
      but more modest increase in the inhibition-associated phosphorylation of GSK3beta
      on Ser-9. Two other inhibitors of histone deacetylase, a recently identified
      target of sodium valproate, also caused gradual increases in the phosphorylation
      of Akt and GSK3beta. Lithium treatment increased the Ser-9 phosphorylation of
      GSK3beta both in cells and in mouse brain after chronic administration, but did
      not alter the phosphorylation of Akt. These results identify novel effects of
      sodium valproate on the Akt/GSK3beta signaling pathway, indicating that histone
      deacetylase inhibition is linked to activation of Akt, and show that two anti
      bipolar agents have a common action, the increased inhibitory phosphorylation of
      Ser-9-GSK3beta. The latter finding, along with previous reports that lithium
      directly inhibits GSK3beta, reveals the possibly unique situation where a single
      target, GSK3beta, is inhibited by two independent mechanisms, directly and by
      phosphorylation following lithium administration, and further, that two mood
      stabilizers have inhibitory effects on GSK3beta.

PMID- 12504923
TI  - Neuropeptide Y receptor subtypes in the basolateral nucleus of the amygdala
      modulate anxiogenic responses in rats.
AB  - The behavioral effects induced by intra-amygdala stimulation of the neuropeptide
      Y (NPY) Y(2) and the NPY Y(5) receptor subtypes were assessed in the social
      interaction (SI) test. Microinjections of NPY(3-36), an NPY Y(2) preferring
      agonist, into the basolateral nucleus of the amygdala (BLA) produced bi
      directional dose-response curve. At low doses NPY(3-36) has an anxiogenic effect
      while at higher doses it produced an anxiolytic effect. Pretreatment with the NPY
      Y(5) receptor antagonist Novartis 1(1 nmol), an analog of CGP71683A synthesized
      by Eli Lilly and Company, IN, blocked the anxiolytic effects of NPY(3-36) (80
      pmol), while pretreatment with BIBO 3304 (200 pmol), a Y(1) antagonist, had no
      effect, suggesting that the Y(5), but not the Y(1) receptor was involved in the
      anxiolytic behavior produced following intra-amygdalar NPY(3-36) administration.
      In addition, the Y(5) antagonist had no behavioral effect when given alone at 1.0
      nmol. These findings support the hypothesis that amygdalar Y(2) receptors may
      play a role in mediating anxiogenic effects, while Y(5) receptors may be involved
      in the anxiolytic behaviors of NPY.

PMID- 12504924
TI  - Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent
      cortical neurons: an essential step for neuroprotection against glutamate
      excitotoxicity.
AB  - Mechanisms underlying the therapeutic effects of lithium for bipolar mood
      disorder remain poorly understood. Recent studies demonstrate that lithium has
      neuroprotective actions against a variety of insults in vitro and in vivo. This
      study was undertaken to investigate the role of the brain-derived neurotrophic
      factor (BDNF)/TrkB signaling pathway in mediating neuroprotection of lithium
      against glutamate excitotoxicity in cortical neurons. Pretreatment with either
      lithium or BDNF protected rat cerebral cortical neurons from glutamate
      excitotoxicity. The duration of treatment required to elicit maximal
      neuroprotection by BDNF (1 day) was much shorter than that by lithium (6 days).
      K252a, an inhibitor of Trk tyrosine kinases, and a BDNF neutralizing antibody
      suppressed the neuroprotective effect of lithium. Treatment of cortical neurons
      with lithium increased the cellular BDNF content in 3 days and the
      phosphorylation of TrkB at Tyr490 in 5 days, suggesting that long-term lithium
      administration enhances BDNF expression/secretion, leading to the activation of
      TrkB receptor. Lithium failed to protect against glutamate excitotoxicity in
      cortical neurons derived from homozygous and heterozygous BDNF knockout mice,
      although lithium fully protected cortical neurons prepared from wild type mice
      littermates. Taken together, these data suggest that the BDNF/TrkB pathway plays
      an essential role in mediating the neuroprotective effect of lithium.

PMID- 12504925
TI  - Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats.
AB  - The analgesic activity of acetyl-L-carnitine (ALCAR) in neuropathic pain is well
      established. By contrast, its potential efficacy in the relief of acute pain has
      not been reported. The antinociceptive effect of ALCAR was, therefore, examined
      in the mouse hot-plate and abdominal constriction tests, and in the rat paw
      pressure test. ALCAR (100 mg kg(-1) s.c. twice daily for seven days) produced an
      increase of the pain threshold in both mice and rats. ALCAR was also able to
      reverse hyperalgesia induced by kainic acid and NMDA administration in the mouse
      hot-plate test. The antinociception produced by ALCAR was prevented by the
      unselective muscarinic antagonist atropine, the M(1) selective antagonists
      pirenzepine and S-(-)-ET126, and by the choline uptake inhibitor hemicholinium-3
      (HC-3). By contrast the analgesic effect of ALCAR was not prevented by the opioid
      antagonist naloxone, the GABA(B) antagonist CGP 35348, the monoamine synthesis
      inhibitor (alpha)-methyl-p-tyrosine, and the Gi-protein inactivator pertussis
      toxin. Moreover, ALCAR antinociception was abolished by pretreament with an
      antisense oligonucleotide (aODN) against the M(1) receptor subtype, administered
      at the dose of 2 nmol per single i.c.v injection. On the basis of the above data,
      it can be postulated that ALCAR exerted an antinociceptive effect mediated by a
      central indirect cholinergic mechanism. In the antinociceptive dose-range, ALCAR
      did not impair mouse performance evaluated by the rota-rod and hole-board tests.

PMID- 12504926
TI  - The use of kinin B1 and B2 receptor knockout mice and selective antagonists to
      characterize the nociceptive responses caused by kinins at the spinal level.
AB  - The mechanisms by which kinins induce hyperalgesia in the spinal cord were
      investigated by using B(1) or B(2) knockout mice in conjunction with kinin
      selective agonists and antagonists. The i.t. administration of the kinin B(2)
      receptor agonists, bradykinin (BK) or Tyr(8)-BK produced dose-related thermal
      hyperalgesia evaluated in the hot-plate test. BK-induced hyperalgesia was
      abolished by the B(2) receptor antagonist Hoe 140. The i.t. injection of the
      kinin B(1) receptor agonists, des-Arg(9)-bradykinin (DABK) or des-Arg(10)
      kallidin (DAKD) also caused dose-related thermal hyperalgesia. Different from the
      B(2) agonists, the i.t. injection of DABK or DAKD caused a weak, but prolonged
      hyperalgesia, an effect that was blocked by the B(1) receptor antagonist des
      Arg(9)-[Leu(8)]-bradykinin (DALBK). The i.t. injection of BK caused thermal
      hyperalgesia in wild-type mice (WT) and in the B(1) receptor knockout mice (B(1)R
      KO), but not in the B(2) receptor knockout mice (B(2)R KO). Similarly, the i.t.
      injection of DABK elicited thermal hyperalgesia in WT mice, but not in B(1)R KO
      mice. However, DABK-induced hyperalgesia was more pronounced in the B(2)R KO mice
      when compared with the WT mice. The i.t. injection of Hoe 140 or DALBK inhibited
      the second phase of formalin (F)-induced nociception. Furthermore, i.t. Hoe 140,
      but not DALBK, also inhibits the first phase of F response. Finally, the i.t.
      injection of DALBK, but not of Hoe 140, inhibits the long-term thermal
      hyperalgesia observed in the ipsilateral and in contralateral paws after
      intraplantar injection with complete Freund's adjuvant. These findings provide
      evidence that kinins acting at both B(1) and B(2) receptors at the spinal level
      exert a critical role in controlling the nociceptive processing mechanisms.
      Therefore, selective kinin antagonists against both receptors are of potential
      interest drugs to treat some pain states.

PMID- 12504927
TI  - Inter-observer variation in assessment of 845 labour admission tests: comparison
      between midwives and obstetricians in the clinical setting and two experts.
AB  - OBJECTIVE: To assess the inter-observer agreement in assessment of the labour
      admission test between midwives and obstetricians in the clinical setting and two
      experts in the non-clinical setting, the inter-observer agreement between two
      experts in the non-clinical setting and to what degree fetal distress in labour
      could be predicted by the two experts. DESIGN: Observational study. SETTING: The
      maternity unit of Hammerfest Hospital, Norway. POPULATION: Eight hundred and
      forty-five high and low risk women. METHOD: The labour admission test was first
      assessed by the midwife or obstetrician in the clinical setting, and was later
      assessed by two experts. The traces were assessed as normal, equivocal or
      ominous. Weighted kappa (kappaw), proportion of agreement (Pa) and predictive
      values were calculated. MAIN OUTCOME MEASURES: Weighted kappa, proportion of
      agreement, sensitivity, positive predictive value and likelihood ratios. RESULTS:
      Inter-observer agreement between Expert 1 and Expert 2: kappaw 0.38 (CI 0.31
      0.46), Pa for reactive labour admission test 0.86 (CI 0.83-0.88) and Pa for
      equivocal/ominous test 0.33 (CI 0.26-0.40). Agreement between Expert 1 and
      midwives/obstetricians: kappaw 0.25 (CI 0.15-0.36), Pa for reactive labour
      admission test 0.89 (CI 0.87-0.91) and Pa for equivocal/ominous labour admission
      test 0.18 (CI 0.11-0.25). Agreement between Expert 2 and midwives/obstetricians:
      kappaw 0.28 (CI 0.20-0.37), Pa for reactive labour admission test 0.85 (CI 0.82
      0.88) and Pa for equivocal/ominous test 0.20 (CI 0.14-0.26). Totally 5.9% of the
      newborns had fetal distress. At cutoff equivocal test, sensitivity was 0.22 and
      0.31 in the two observers. Positive predictive values were 0.13 and 0.11.
      Likelihood ratio for a positive test was 2.30 and 1.92 and likelihood ratio for a
      negative test 0.86 and 0.83. CONCLUSION: A labour admission test is still routine
      practice in most obstetric units in the Western world when there is little
      evidence on its benefits. The results from this study may provide some
      reconsideration for such practice, and for more research.

PMID- 12504928
TI  - Cerebral palsy and clinical negligence litigation: a cohort study.
AB  - OBJECTIVE: To compare the prevalence of criteria suggesting acute intrapartum
      hypoxia in children with cerebral palsy who have and have not been the subjects
      of clinical negligence legal claims. DESIGN: Nested cohort study within a
      geographically defined cohort. SETTING: The former Oxfordshire Health Authority.
      POPULATION: Singleton children with cerebral palsy born between 1984 and 1993,
      excluding cases with a recognised postnatal cause for cerebral palsy. METHODS:
      Retrospective review of medical records by blinded observer. MAIN OUTCOME
      MEASURES: Three 'essential' criteria defined by the International Cerebral Palsy
      Task Force which identify acute intrapartum hypoxia. RESULTS: One-fifth (27/138)
      of all singleton cerebral palsy children were the subject of a legal claim. The
      presence of all three criteria was significantly more likely to lead to a legal
      claim (P < 0.01), but in 74% (20/27) of claims, all three were not fulfilled and
      36% (4/11) of those satisfying all three criteria did not claim. At least one of
      the three criteria was met in 82% (91/111) of the cases where there was no claim.
      Data on fetal or neonatal arterial blood gases were available in only 57%
      (78/138). Of the 27 claims, 12 were discontinued, 8 were settled and in 7 the
      legal process is still pending. The presence of the three essential criteria for
      acute intrapartum hypoxia did not increase the likelihood of a legal claim being
      settled. CONCLUSION: The prevalence of the 'template essential' criteria is high
      in all cases of cerebral palsy. Although the presence of all three essential
      criteria was more likely in the claims group, this did not appear to influence
      the outcome of a claim. It remains to be seen whether the existence of the
      template leads to change in the pattern of decisions made by the courts.

PMID- 12504929
TI  - Assessing urinary albumin excretion in pre-eclamptic women: which sample to use?
AB  - OBJECTIVE: To evaluate whether the gold standard of 24-hour urine collection for
      measuring albumin excretion in pre-eclamptic women could be substituted by
      shorter collection periods. DESIGN: Prospective study. SETTING: Fetal maternity
      ward, university hospital. PARTICIPANTS: Thirty women with pre-eclampsia and a
      positive urinary test strip for protein of at least 2+. METHODS: From each woman,
      within a 25-hour period, three spot, two 12-hour (day and night) and one 24-hour
      urine sample were collected. Urine albumin concentrations in milligrammes per
      litre were analysed by rate nephelometry on a Beckman Array protein system. The
      urinary albumin concentrations in the spot and the 12-hour samples were compared
      with the concentration in the 24-hour urine collection. MAIN OUTCOME MEASURES:
      Urinary albumin concentrations in spot and 12-hour samples measured against the
      standard 24-hour albumin excretion. RESULTS: Albumin concentrations in the day
      and night collection fitted closely with the concentrations of the 24-hour
      collection. The median difference between the 24-hour and the day collection was 
      3 mg/L (interquartile range -264 to 116 mg/L). The median difference between the
      24-hour and the night collection was 17 mg/L (interquartile range -186 to 210
      mg/L). The association of urinary albumin concentration in the 24-hour collection
      and the spot samples was much weaker. Of the spot urine samples, the albumin
      concentration in the sample taken on the morning after admission to hospital was
      closest to the 24-hour urinary albumin excretion, with a median difference of -62
      mg/L (interquartile range -1131 to 285 mg/L). CONCLUSION: The gold standard of 24
      hour urinary excretion for assessment of albuminuria in pre-eclamptic women can
      be substituted with a 12-hour collection. Spot urine samples were inaccurate and
      are therefore not recommended for quantification of albumin excretion.

PMID- 12504930
TI  - Fetuses with Down's Syndrome detected by prenatal screening are more likely to
      abort spontaneously than fetuses with Down's Syndrome not detected by prenatal
      screening.
AB  - OBJECTIVE: Pregnancy with Down's Syndrome is often terminated by miscarriage. We
      have investigated whether prenatal screening would lead preferentially to the
      identification of fetuses with Down's Syndrome prone to abort spontaneously.
      DESIGN: A comparison between the observed and the expected decrease in the
      prevalence of Down's Syndrome at term following extensive prenatal screening.
      SETTING: A study from 1990 to 1998 in a limited and well controlled area of
      western France (Basse Normandie), with a birth rate close to 20,000 a year.
      POPULATION: Women under 38 years of age among whom prenatal screening for Down's
      Syndrome using biochemical tests and ultrasound findings became progressively
      extensive in this era. METHODS: Our study was based on the registration of Down's
      Syndrome cases detected prenatally from screening, and live births with Down's
      Syndrome. Fetal loss rate in the population of prenatally detectable Down's
      Syndrome was evaluated by comparing the increase in detection of cases of Down's
      Syndrome following prenatal screening with the expected decrease in the number of
      cases of Down's Syndrome at birth. The results obtained were compared with
      published data on the rates of fetal losses postulated to occur among fetuses
      with Down's Syndrome. MAIN OUTCOME MEASURES: Comparison of the potential fetal
      loss rate in a population in whom Down's Syndrome was detected prenatally with
      the expected fetal loss rate of unselected ones. RESULTS: Prenatal screening
      resulted in a significant (42%) decrease (P < 0.001) in the prevalence at term of
      the disorder. Among the 53 fetuses with Down's Syndrome detected prenatally
      during the last three years of the study, about 50% would have aborted
      spontaneously if the pregnancy had been allowed to continue. This figure was
      significantly higher (P < 0.002) than expected on the basis of results from the
      literature, indicating that current estimates of miscarriage rates among fetuses
      with Down's Syndrome do not apply to the selected group of cases detectable from
      prenatal screening. CONCLUSIONS: Our results suggest that fetuses with Down's
      Syndrome detectable prenatally from screening are more likely to abort
      spontaneously than fetuses with Down's Syndrome which are not detected.

PMID- 12504931
TI  - Risk of recurrent hydatidiform mole and subsequent pregnancy outcome following
      complete or partial hydatidiform molar pregnancy.
AB  - OBJECTIVE: To determine pregnancy outcome, including the rate of repeat molar
      pregnancy, following histologically confirmed complete or partial hydatidiform
      mole. DESIGN: Retrospective review of a large supraregional database of
      registrations for gestational trophoblastic disease. SETTING: Supraregional
      Trophoblastic Disease Unit, London. SAMPLE: Women with pregnancies affected by
      complete or partial hydatidiform mole registered between 1992 and 1998. METHODS:
      All patients with a diagnosis of histologically confirmed complete or partial
      hydatidiform mole were identified and data on subsequent pregnancies compared
      between groups using comparison of proportion test. MAIN OUTCOME MEASURES:
      Pregnancy outcome by partial or complete mole subtype, with particular regard to
      risk of subsequent molar pregnancy. RESULTS: Of 2578 complete moles, the
      subsequent pregnancy was affected by hydatidiform mole in 27 (1.9%) cases,
      including 22 (81%) complete moles and 5 (19%) partial moles. Of 2627 partial
      moles, the subsequent pregnancy was also molar in 25 (1.7%) cases, including 17
      (68%) partial moles and 8 (32%) complete moles. Overall recurrence risk for molar
      pregnancy was 1.8% (1 in 55), or a 20-fold increase compared with the background
      risk. Of 27 cases with repeat complete moles, three had further complete moles,
      suggesting the recurrence risk following two previous complete moles is
      approximately 10%. There were no other significant differences in pregnancy
      outcome between cases with previous complete or partial hydatidiform mole and
      that expected in an unselected obstetric population. CONCLUSIONS: Women having a
      pregnancy affected by a histologically confirmed complete or partial hydatidiform
      mole may be counselled that the risk of repeat mole in a subsequent pregnancy is
      about 1 in 60 and if this were to occur, the majority of cases will be of the
      same type of mole as the preceding pregnancy. However, >98% of women who become
      pregnant following a molar conception will not have a further hydatidiform mole
      and these pregnancies are at no increased risk of other obstetric complications.

PMID- 12504932
TI  - A randomised trial of timed delivery for the compromised preterm fetus: short
      term outcomes and Bayesian interpretation.
AB  - OBJECTIVES: To compare the effect of delivering early to pre-empt terminal
      hypoxaemia with delaying for as long as possible to increase maturity. DESIGN: A
      randomized controlled trial. SETTING: 69 hospitals in 13 European countries.
      PARTICIPANTS: Pregnant women with fetal compromise between 24 and 36 weeks, an
      umbilical artery Doppler waveform recorded and clinical uncertainty whether
      immediate delivery was indicated. METHODS: The interventions were 'immediate
      delivery' or 'delay until the obstetrician is no longer uncertain'. The data
      monitoring and analysis were Bayesian. MAIN OUTCOME MEASURES: 'Survival to
      hospital discharge' and 'developmental quotient at two years of age', this latter
      to be reported later. RESULTS: Of 548 women (588 babies) recruited, outcomes were
      available on 547 mothers (587 babies). The median time-to-delivery intervals were
      0.9 days in the immediate group and 4.9 days in the delay group. Total deaths
      prior to discharge were 29 (10%) in the immediate group versus 27 (9%) in the
      delay group (odds ratio 1.1, 95% CI 0.61-1.8). Total caesarean sections were 249
      (91%) in the immediate group versus 217 (79%) in the delay group: (OR 2.7; 95% CI
      1.6-4.5). These odds ratios were similar for those randomized at gestational ages
      above or below 30 weeks. INTERPRETATION: The lack of difference in overall
      mortality suggests that clinicians participating in this trial were on average
      prepared to randomize at about the correct equivocal threshold between delivery
      and delay. However, there was insufficient evidence to convince enthusiasts for
      either immediate or delayed delivery that they were wrong.

PMID- 12504933
TI  - Distribution of fetal erythroblasts in maternal blood after chorionic villous
      sampling.
AB  - OBJECTIVE: To investigate whether chorionic villus sampling (CVS) is associated
      with an increase in fetomaternal cell trafficking. DESIGN: Prospective study.
      SETTING: King's College London School of Medicine, King's College Hospital.
      SAMPLE: Eighteen singleton pregnancies undergoing CVS for fetal karyotyping at 11
      14 weeks of gestation and subsequently found to have chromosomal defects. METHOD:
      Maternal blood samples were obtained immediately before and at 3-14 (median 5)
      days after CVS. Fetal erythroblasts were isolated using triple density gradient
      separation and anti-CD71 magnetic cell sorting techniques. The enriched
      erythroblasts were stained with Kleihauer-Giemsa and with fluorescent antibodies
      for the epsilon (epsilon) and gamma (gamma) globin chains. The percentage of
      fetal cells positive for each stain was calculated. Fluorescence in situ
      hybridisation (FISH) for X- and Y-chromosomes was also performed. Comparison was
      made in the proportion of enriched fetal cells between the pre-CVS and post-CVS
      samples. MAIN OUTCOME MEASURES: The proportion of fetal erythroblasts in maternal
      blood. RESULTS: The percentage of erythroblasts enriched from maternal blood that
      stained positive for epsilon and gamma globin chains and with Kleihauer-Giemsa
      was significantly higher in the post-CVS samples compared with the pre-CVS
      samples. FISH analysis for the Y-chromosome confirmed the increase in fetal cell
      proportion in the post-CVS samples. The percentage difference in fetal cells
      decreased significantly with time interval from CVS. CONCLUSION: CVS results in
      an increase in fetomaternal cell trafficking, which continues to be present for
      several days after the procedure.

PMID- 12504934
TI  - Pharmacokinetics of anti-D IgG in pregnant RhD-negative women.
AB  - OBJECTIVE: To assess the pharmacokinetics of anti-D IgG in pregnant Rhesus D
      negative women after intramuscular and intravenous administration of 300 microg
      of Rhophylac. DESIGN: An open, randomised, multicentre study. SETTING: Seven
      gynaecological practices in Germany. SAMPLE: Fourteen RhD-negative pregnant women
      at risk of becoming Rhesus D immunised received study drug at 28th week of
      pregnancy either by intramuscular or intravenous route. MAIN OUTCOME MEASURES:
      Anti-D IgG concentrations of serum samples obtained up to 11 weeks following
      antenatal Rhesus D prophylaxis were quantified by flow cytometry. RESULTS: Mean
      anti-D IgG concentrations after intravenous and intramuscular administration
      differed up to seven days post-injection, from two weeks onwards they were
      comparable to each other. Irrespective of the administration route, anti-D IgG in
      serum was detectable in all women up to at least nine weeks post-administration.
      CONCLUSIONS: The serum concentrations of anti-D IgG measured after administration
      of Rhophylac were very similar to those obtained with 300 microg of a different
      anti-D immunoglobulin product.

PMID- 12504935
TI  - Maternal serum activin, inhibin, human chorionic gonadotrophin and alpha
      fetoprotein as second trimester predictors of pre-eclampsia.
AB  - OBJECTIVE: To compare the serum levels of human chorionic gonadotrophin (hCG),
      alpha-fetoprotein, activin A, inhibin A and inhibin isoforms containing pro and
      alphaC in the second trimester serum of women who subsequently developed
      hypertensive disorders of pregnancy with those who remained normotensive
      throughout pregnancy. DESIGN: Retrospective case-control study of 15-20 week
      serum samples matched for duration of storage at -20 degrees C. SETTING:
      Antenatal clinics at a teaching hospital in Scotland. SAMPLE: Second trimester
      serum samples of 39 women who subsequently developed pre-eclampsia, 31 who
      subsequently developed pregnancy-induced hypertension and 155 women who remained
      normotensive throughout pregnancy. MAIN OUTCOME MEASURES: hCG, alpha-fetoprotein,
      activin A, inhibin A and inhibin pro-alphaC serum levels. RESULTS: Activin A
      levels in serum were significantly elevated in women who later developed
      pregnancy-induced hypertension (26% increase compared with controls) and hCG
      levels were significantly elevated in women who later developed pre-eclampsia
      (24% increase compared with controls). alpha-Fetoprotein, inhibin A and inhibin
      pro-alphaC levels were not significantly elevated in the patient groups compared
      with their controls. CONCLUSIONS: A combination of analyses including second
      trimester serum activin A and hCG may yet prove to be helpful predictors of women
      at risk of hypertensive disorders of pregnancy. While the results proved
      significant, the effects reported in this study are too modest compared with
      natural variability to be useful as screening tools on their own.

PMID- 12504936
TI  - Gene expression of nitric oxide synthase by human umbilical vein endothelial
      cells: the effect of fetal plasma from pregnancy with umbilical placental
      vascular disease.
AB  - OBJECTIVE: To determine whether endothelial cell injury would be produced by
      factor(s) released into the fetal circulation, manifested by altered messenger
      RNA expression of nitric oxide synthase. DESIGN: Case-control study. SETTING:
      University teaching hospital. SAMPLES: Fetal plasma was collected from 34 normal
      pregnancies, 44 pregnancies with umbilical placental vascular disease identified
      by an abnormal umbilical Doppler and 11 pregnancies with maternal pre-eclampsia
      but with normal umbilical Doppler studies. METHODS: Aliquots from a common
      culture of human umbilical vein endothelial cells (HUVECs) were incubated with
      fetal plasma from the members of the three patient groups. The total RNA was
      extracted from the endothelial cells and mRNA for nitric oxide synthase was
      measured by reverse transcription and semi-quantitative polymerase chain reaction
      (RT-PCR). This was standardised by comparison of the amplified inducible nitric
      oxide synthase (iNOS) or endothelial constitutive nitric oxide synthase (ecNOS)
      to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). MAIN OUTCOME MEASURE:
      Endothelial cell gene expression of iNOS and ecNOS. RESULTS: The mRNA expression
      of iNOS and ecNOS were significantly higher (P < 0.05) in HUVECs stimulated by
      fetal plasma from pregnancies with umbilical placental vascular disease [iNOS
      1.12 (0.16); ecNOS 1.78 (0.18)] when compared with normal pregnancies [iNOS 0.56
      (0.06); ecNOS 1.06 (0.10)]. In the maternal pre-eclampsia group, the NOS
      expression [iNOS 0.76 (0.11); ecNOS 1.39 (0.26)] did not differ from normal
      pregnancy. In the vascular disease group, there was no difference in NOS
      expression between the subgroups with and without maternal pre-eclampsia.
      CONCLUSIONS: Our study demonstrates that umbilical placental vascular disease is
      associated with a factor(s) in fetal plasma that produces an increase in the
      expression of iNOS and ecNOS mRNA by endothelial cells. Our findings raise the
      possibility that the release of factors causing an up-regulation of iNOS and
      ecNOS in the endothelium in the fetal placenta may occur as part of an
      inflammatory response of the vascular endothelium to injury.

PMID- 12504937
TI  - Premature ovarian failure: frequency and risk factors among women attending a
      network of menopause clinics in Italy.
AB  - OBJECTIVE: To determine the frequency and causes of preterm ovarian failure
      (menopause before 40 years of age) and early menopause (menopause between 40 and
      45 years). DESIGN: Cross sectional study. SETTING: Menopause clinics in Italy.
      POPULATION: Women attending menopause clinics in Italy. METHODS: Between 1997 and
      1999 we conducted a large cross sectional study on the characteristics of women
      around menopause attending a network of first-level outpatient menopause clinics
      in Italy for general counselling about menopause or treatment of menopausal
      symptoms. Eligible for the study were all women aged 45-75 years consecutively
      observed for the first time at the participating centres on randomly selected
      days during the study period. MAIN OUTCOME MEASURE: Factors associated with
      preterm ovarian failure. RESULTS: Out of 15,253 women aged 55 years or more with
      spontaneous menopause who entered the study, 269 (1.8%) reported preterm ovarian
      failure, and 1085 (7.1%) reported spontaneous menopause at age 40-45 years. The
      risk of preterm ovarian failure and of early menopause was higher in women
      reporting lifelong irregular menstrual cycles: in comparison with women reporting
      menopause at age > or =45 years, the OR (irregular vs regular menstrual cycles)
      of preterm ovarian failure was 1.3 (95% CI 1.0-1.7) and of early menopause of 1.2
      (95% CI 1.0-1.5). Parous women reported less frequently preterm ovarian failure
      (chi(2) trend P < 0.05) and early menopause (OR 0.8, 95% CI 0.7-1.0). No
      significant association emerged between risk of preterm ovarian failure or
      menopause at age 40 to <45 and education, age at menarche, oral contraceptive use
      and smoking habits. CONCLUSION: Nulliparity and lifelong irregular menstrual
      cycles are associated with an increased risk of preterm ovarian failure.

PMID- 12504938
TI  - Serum profile of isosorbide mononitrate after vaginal administration in the third
      trimester.
AB  - Vaginally administered nitric oxide donors such as isosorbide mononitrate have
      been used to ripen the uterine cervix in pregnancy. The pharmacokinetics of
      isosorbide mononitrate following vaginal administration are unknown. Serum levels
      of isosorbide mononitrate were determined at baseline and 60, 180 and 360 minutes
      after vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant
      women scheduled for induction of labour at term. Serum levels of isosorbide
      mononitrate continued to rise up to 360 minutes after isosorbide mononitrate
      insertion, with mean (SD) final levels of 337 (94) microg/L following isosorbide
      mononitrate 40 mg and 144 (47) microg/L following isosorbide mononitrate 20 mg, P
      < 0.01.

PMID- 12504939
TI  - Selective termination of a twin pregnancy as a treatment of severe pre-eclampsia.

PMID- 12504940
TI  - Prenatal treatment of chorioangioma by microcoil embolisation.

PMID- 12504941
TI  - Neonatal gangrene in an extremity of an infant of a diabetic mother.

PMID- 12504942
TI  - Reversible ovarian failure induced by a Chinese herbal medicine: lei gong teng.

PMID- 12504943
TI  - Postural perineal pain associated with perforation of the lower urinary tract due
      to insertion of a tension-free vaginal tape.

PMID- 12504944
TI  - Evaluating ambulatory urodynamics: a prospective study in asymptomatic women.

PMID- 12504945
TI  - Intrafascial hysterectomy: the third way?

PMID- 12504946
TI  - Sacrohysteropexy with synthetic mesh for the management of uterovaginal prolapse.

PMID- 12504947
TI  - Fetal and maternal lactate increase during active second stage of labour.

PMID- 12504948
TI  - The aetiology of parous endometriosis.

PMID- 12504949
TI  - Fetal and maternal lactate increase during active second stage of labour (what
      about the effect of maternal analgesia?).

PMID- 12504950
TI  - Fetal postmortem weight loss in utero.

PMID- 12504951
TI  - Somalis in Sweden: are bigger babies better?

PMID- 12504952
TI  - The effectiveness of the levonorgestrel-releasing intrauterine system in
      menorrhagia: a systematic review.

PMID- 12504953
TI  - Remote consequences of transcervical resection of the endometrium.

PMID- 12504954
TI  - Randomised, double-blind, placebo-controlled trial of corticosteroids for the
      treatment of hyperemesis gravidarum.

PMID- 12504955
TI  - The prevalence of pelvic floor disorders and their relationship to gender, age
      and mode of delivery.

PMID- 12504956
TI  - Effectiveness and safety of the oxytocin antagonist atosiban versus beta
      adrenergic agonists in the treatment of preterm labour.

PMID- 12504957
TI  - The tension free vaginal tape procedure is successful in the majority of women
      with indications for surgical treatment of urinary stress incontinence.

PMID- 12504958
TI  - Risk factors for third degree perineal ruptures during delivery.

PMID- 12504959
TI  - Effects of mode of delivery and infant feeding on the risk of mother-to-child
      transmission of hepatitis C virus.

PMID- 12504960
TI  - Avoiding inadvertent laparoelytrotomy.

PMID- 12504961
TI  - Venous malformation of the vulva.

PMID- 12504962
TI  - Endometrial laser intrauterine thermotherapy for the treatment of dysfunctional
      uterine bleeding.

PMID- 12504964
TI  - A critique of cohort studies examining the role of human papillomavirus infection
      in cervical neoplasia.

PMID- 12504965
TI  - Patterns of use of hormone replacement therapy in one million women in Britain,
      1996-2000.
AB  - OBJECTIVE: To describe national patterns of use of hormone replacement therapy
      (HRT) in 1996-2000. DESIGN: Population-based study of women aged 50-64. SETTING:
      England and Scotland. POPULATION: A total of 1,091,250 women were recruited
      between May 1996 and December 2000. METHODS: Women invited for screening at 66
      NHS breast screening units were sent a questionnaire to complete before they were
      screened; 71% of women screened participated. Prevalence of use of HRT. RESULTS:
      Overall, 33% of women reported that they were currently using HRT, the average
      duration of use being 5.8 years; 50% were ever-users. Current use of HRT was
      about twice as common at age 50-54 than 60-64, but varied little by time or
      region, the prevalences being 33%-34% in each year from 1996 to 2000; 30% in
      Scotland and 35% in southeast England. The prevalence of current use of HRT
      varied substantially depending on the woman's history of gynaecological surgery
      and past health, and was as follows in women with a history of: bilateral
      oophorectomy (66%); hysterectomy without bilateral oophorectomy (48%); neither
      hysterectomy nor bilateral oophorectomy (27%); breast cancer (6%); other cancer
      (25%); stroke (24%); venous thromboembolism (24%); diabetes (25%); heart disease
      (31%); or hypertension (31%). There was considerably less variation in the
      prevalence of use of HRT according to deprivation index, education, parity, body
      mass index, exercise, smoking or alcohol consumption. CONCLUSIONS: HRT is
      currently used by around one-third of women aged 50-64 in Britain and appears to
      be influenced considerably more strongly by a woman's medical and surgical
      history than by socio-economic or lifestyle factors.

PMID- 12504966
TI  - Reproductive performance after hysteroscopic metroplasty in the hypoplastic
      uterus: a study of 29 cases.
AB  - OBJECTIVE: To evaluate the reproductive performance after hysteroscopic
      metroplasty performed for hypoplastic uterus. DESIGN: Crossover study (15
      patients) and descriptive analysis (14 patients). SETTING: Tertiary care
      university hospital. POPULATION: Twenty-nine women (mean age: 31.4 years; range:
      27-38.5 years) with a hypoplastic malformed uterus and a history of primary
      infertility and/or recurrent abortion and/or preterm delivery were included in
      this study. Fourteen women suffered from primary infertility and 15 women had
      previous pregnancies. Twenty-three women had been exposed to diethylstilboestrol
      in utero. METHODS: Women underwent hysteroscopic metroplasty between January 1996
      and May 1999. MAIN OUTCOME MEASURES: Rate of pregnancies and live births,
      anatomical results. RESULTS: The mean follow up was 40 months (range: 13-67
      months). Twenty-one women (72.4%) experienced 30 pregnancies. Thirteen women gave
      birth to 16 live infants. At the time of the follow up, four women were pregnant
      in the second trimester. Compared with previous pregnancies, the rate of
      deliveries increased from 3.8% to 63.2%. No complications occurred during
      metroplasty. The hysteroscopic anatomical results were good in all cases.
      CONCLUSIONS: Our results suggest that hysteroscopic metroplasty, with its
      simplicity and minimal post-operative sequelae, seems to be an operation of
      choice in women with a hypoplastic malformed uterus and a history of severe
      infertility and/or recurrent pregnancy loss.

PMID- 12504967
TI  - Listening to patients with unexplained menstrual symptoms: what do they tell the
      gynaecologist?
AB  - OBJECTIVES: To describe how women present unexplained menstrual symptoms to
      gynaecologists; to find out whether presentation reflects how intense their
      symptoms feel or how much benefit they expect from gynaecological treatment; and
      to test the prediction that surgical treatment decisions are more likely to
      follow specific types of presentation. DESIGN: A cross sectional cohort study.
      SETTING: Gynaecological outpatient clinics in a teaching hospital. SAMPLE: Fifty
      nine patients, referred for menstrual problems, in whom investigations had
      excluded physical disease. METHODS: Patients indicated symptom intensity and
      expectations of treatment before consultation on self-completed questionnaires.
      Audiotape recordings of consultations with the gynaecologist were transcribed and
      patients' use of specific communication strategies was coded according to a
      previously reported scheme. MAIN OUTCOME MEASURES: Treatment decision was noted.
      RESULTS: In a third to a half of patients, presentation extended beyond symptom
      report to include catastrophisation about consequences of symptoms, reference to
      other individuals to substantiate the patient's problems, criticism of previous
      or possible future interventions or request for hysterectomy. Those with greatest
      expectations of gynaecological treatment were more likely to catastrophise and
      request hysterectomy. Those with most intense subjective symptoms were more
      likely to catastrophise, refer to other individuals and request hysterectomy, and
      these strategies were more likely to be followed by surgical treatment decisions.
      CONCLUSIONS: Surgical treatment for unexplained menstrual problems is not driven
      by gynaecologists. Reduction in unnecessary hysterectomies will require training
      in communication skills that reflects the challenging nature of many patients'
      presentation in the gynaecology clinic.

PMID- 12504968
TI  - The effect of the publication of a major clinical trial in a high impact journal
      on clinical practise: the ORACLE Trial experience.
AB  - OBJECTIVE: To estimate the short term effect of the publication of a major
      clinical trial on clinical practise. DESIGN: Questionnaire survey of clinical
      practise. SETTING: UK. POPULATION: All maternity units in the UK. METHOD: A self
      administered questionnaire completed by lead consultants on delivery suite of
      maternity units. MAIN OUTCOME MEASURES: Changes in antibiotic prescription.
      RESULTS: Within six months of publication, approximately 50% of maternity units
      had changed their guidelines for the care of women with preterm prelabour rupture
      of the fetal membranes. CONCLUSION: Publication of a major clinical trial does
      impact on clinical practise but the impact is heterogeneous in terms of time and
      consistency.

PMID- 12504969
TI  - Analgesia in labour and fetal acid-base balance: a meta-analysis comparing
      epidural with systemic opioid analgesia.
AB  - OBJECTIVE: To assess the effect of epidural versus systemic labour analgesia on
      funic acid-base status at birth. DESIGN: A systematic review of trials, both
      randomised and non-randomised, comparing epidural with systemic opioid analgesia.
      POPULATION: Babies of 2102 mothers taking part in trials comparing epidural with
      systemic analgesia in five countries. METHODS: From the published and unpublished
      figures obtained from authors, fetal pH data from 12 studies (eight randomised)
      (1098 babies in the epidural group + 1004 controls) and base excess from 8
      studies (four randomised) (856 epidural + 842 controls) were subjected to random
      effect meta-analysis. MAIN OUTCOME MEASURES: Umbilical artery pH and base excess
      values. RESULTS: Fetal pH was higher in the epidural than in the control group in
      the randomised trials (difference +0.009, 95% CI +0.002 to +0.015), but when all
      studies were included, the difference was not significant (+0.004, 95% CI -0.005
      to +0.014). Fetal base excess was higher in the epidural group in the four
      randomised studies (difference +0.779 mEq/L, 95% CI +0.056 to +1.502) and in all
      eight studies (difference +0.837 mEq/L, 95% CI +0.330 to +1.343). CONCLUSION:
      Umbilical artery pH is influenced by maternal hyperventilation. Base excess is
      therefore a better index of metabolic acidosis after labour. Epidural analgesia
      is associated with improved neonatal acid-base status, suggesting that placental
      exchange is well preserved in association with maternal sympathetic blockade and
      good analgesia. Although epidural analgesia may cause maternal hypotension and
      fever, longer second stage of labour and more instrumental vaginal deliveries,
      these potentially adverse factors appear to be outweighed by benefits to neonatal
      acid-base status.

PMID- 12504970
TI  - Active management of term prelabour rupture of membranes with oral misoprostol.
AB  - OBJECTIVE: To compare the active management of term prelabour rupture of
      membranes with oral misoprostol with conservative management for 24 hours
      followed by induction with oxytocin or prostaglandin E(2) (PGE(2)) gel. DESIGN: A
      non-blinded randomised controlled trial. SETTING: Induction and labour wards,
      Aberdeen Maternity Hospital. POPULATION: Sixty-one women with confirmed prelabour
      rupture of the membranes at > or =36 weeks of gestation. METHODS: The women were
      randomised to 50 microg of oral misoprostol repeated every 4 hours, if required,
      to a maximum of five doses (active group), or to induction of labour with PGE(2)
      gel or oxytocin only if not in spontaneous labour 24 hours after prelabour
      rupture of membranes (conservative group). MAIN OUTCOME MEASURES: Number of women
      in active labour within 24 hours of the prelabour rupture of membranes,
      preference of women for any one particular method of management in any subsequent
      pregnancy with prelabour rupture of membranes. RESULTS: 93.3% of the active group
      and 54.8% of the conservative group were in spontaneous labour within 24 hours of
      the prelabour rupture of membranes (RR 1.7, 95% CI 1.2 to 2.4). Of those
      achieving a vaginal delivery, 72% of the active group did so within 24 hours of
      the prelabour rupture of membranes as compared with 26.9% of the conservative
      group (RR 2.7, 95% CI 1.4 to 5.3, P = 0.002). There were no significant
      differences in the neonatal or maternal outcomes. In the active group, 78% felt
      they would have the same method of induction as compared with 40% in the
      conservative group (RR 1.9, 95% CI 1.1 to 3.3, P = 0.03). CONCLUSIONS: Active
      management with oral misoprostol resulted in more women going into labour and
      delivering within 24 hours of the prelabour rupture of membranes with no increase
      in maternal or neonatal complications. Women tended to view active management of
      prelabour rupture of membranes more positively. Oral misoprostol might be an
      option to consider in those wishing active management.

PMID- 12504971
TI  - A randomised clinical trial comparing the effects of delayed versus immediate
      pushing with epidural analgesia on mode of delivery and faecal continence.
AB  - OBJECTIVE: To assess the effects of delayed vs immediate pushing in second stage
      of labour with epidural analgesia on delivery outcome, postpartum faecal
      continence and postpartum anal sphincter and pudendal nerve function. DESIGN:
      Prospective, randomised, controlled trial.Tertiary referral maternity teaching
      hospital. POPULATION: One hundred and seventy nulliparous women randomised at
      full dilatation to immediate or delayed pushing. METHODS: A total of 178
      nulliparous women, all with continuous epidural analgesia, were randomised at
      full cervical dilatation, but before the fetal head had reached the pelvic floor,
      to either immediate pushing or 1 hour delayed pushing. Labour outcome was
      analysed and all women underwent postpartum assessment of anal sphincter
      function, including anal manometry. Those women who had a normal delivery
      underwent neurophysiology studies, while those women who had an instrumental
      delivery underwent endoanal ultrasound. MAIN OUTCOME MEASURES: Mode of delivery;
      altered faecal continence. RESULTS: Ninety women were randomised to immediate
      pushing and 88 to delayed pushing. The spontaneous delivery rate was 56% (50/90)
      in the immediate pushing group and 52% (46/88) in the delayed pushing group. Mean
      duration of labour for the immediate pushing group was 427 minutes compared with
      480 minutes for the delayed pushing group (P = 0.005). Eighty-four percent
      (76/90) of women in the immediate pushing group received oxytocin to augment
      labour, 21/76 (28%) in the second stage only. Eighty-one percent (71/88) of women
      in the delayed pushing group received oxytocin to augment labour, 22/71 (31%) in
      the second stage only. Fetal outcome did not differ between the two groups.
      Episiotomy rates were 73% and 69% in the immediate pushing and delayed pushing
      groups, respectively. 26% (23/90) of the immediate pushing group and 38% (33/88)
      of the delayed pushing group complained of altered faecal continence after
      delivery (NS). Manometry, ultrasound and neurophysiology studies did not differ
      significantly between the two groups. Overall, 55% of women after instrumental
      delivery had endosonographic evidence of damage to the external anal sphincter,
      while 36% of women after spontaneous delivery had abnormal neurophysiology
      studies. CONCLUSIONS: Rates of instrumental delivery were similar following
      immediate and delayed pushing, in association with epidural analgesia. Delayed
      pushing prolonged labour by 1 hour but did not result in significantly higher
      rates of altered continence or anal sphincter injury, when compared with
      immediate pushing.

PMID- 12504972
TI  - Endemic goiter in pregnant women: utility of the simplified classification of
      thyroid size by palpation and urinary iodine as screening tests.
AB  - OBJECTIVE: To validate urinary iodine (I) excretion and the simplified
      classification of goiter by palpation, comparing them with ultrasound of the
      thyroid gland as the gold standard, to identify endemic goiter in pregnant women.
      POPULATION AND SETTING: 300 pregnant women identified in referral hospitals, in
      three geographic regions. METHODS: Two endocrinologists, previously trained,
      evaluated thyroid size by palpation and by ultrasound. Urinary iodine excretion
      in a sample of urine was determined. Thyroid size below the 90th centile by
      ultrasound was considered normal. RESULTS: Mean age of study women was 23 years
      old. The prevalence of low weight for gestational age was 39% and of anaemia 47%.
      Our sample distribution showed that 120 microg I/L was the best cut off for low
      urinary iodine excretion to identify endemic goiter in pregnant women
      (sensitivity 57% and specificity 70%, likelihood ratio of 1.4). The prevalence of
      goiter was 10% using ultrasound. Palpation had a sensitivity of identification
      goiter of 94% (95% CI 89-99%), a specificity of 80% (95% CI 75-85%), a likelihood
      ratio of 4.7, positive post-test probability of 36.5% and negative post-test
      probability of 99%. CONCLUSIONS: Low urinary iodine excretion identified up to
      46% of women with goiter. This test by itself is not useful as a screening tool
      to identify pregnant women at risk of goiter. Identification of thyroid size by
      palpation was a better screening test. However, when both tests were combined in
      parallel, up to 100% of women with goiter were correctly identified. Our results
      suggest that the commonly used cut off point of 100 microg I/L to identify low
      urinary iodine excretion may under-estimate the prevalence of iodine deficiency
      disorders when used during pregnancy.

PMID- 12504973
TI  - Mid-trimester severe intrauterine growth restriction is associated with a high
      prevalence of thrombophilia.
AB  - OBJECTIVE: To investigate the association between severe mid-trimester IUGR,
      whose causes are unknown in most cases, and maternal thrombophilias. DESIGN: Case
      control study. SETTING: Lis Maternity Hospital, Tel Aviv Sourasky Medical Center,
      The Sackler Faculty of Medicine, Tel Aviv University. POPULATION: Twenty-six
      women with severe mid-trimester (22-26 weeks of gestation) IUGR (birthweight <3rd
      centile) and 52 matched multiparous women with normal pregnancies (controls).
      METHODS: After excluding pregnancies with vascular maternal disease, chromosomal
      and structural aberrations and cytomegalovirus infection, 26 women out of 35 with
      severe mid-trimester IUGR remained and composed the study group. Each was matched
      for age, ethnicity and smoking status with two healthy women who had normal
      pregnancies. All the women were tested for genetic and acquired thrombophilias at
      least eight weeks after delivery. MAIN OUTCOME MEASURES: Prevalence of maternal
      thrombophilias. RESULTS: The frequency of thrombophilias was 69% in the study
      group compared with 14% in the control group [odds ratio (OR) 4.5; 95% confidence
      interval (CI) 2.3-9, P < 0.001]. The frequencies of factor V Leiden mutation,
      prothrombin gene mutation and protein S deficiency were significantly increased
      in the study group compared with the control group. The frequency of multiple
      thrombophilias was 33% in the study group versus none among the controls. Of the
      26 pregnancies with severe mid-trimester IUGR, 13 ended in intrauterine fetal
      death before 25 weeks of gestation: 10 of these women had thrombophilia.
      CONCLUSION: Women with mid-trimester severe IUGR have an increased prevalence of
      inherited and acquired thrombophilias.

PMID- 12504974
TI  - Anti-shock garment provides resuscitation and haemostasis for obstetric
      haemorrhage.
AB  - OBJECTIVE: To evaluate the feasibility, safety and effectiveness of the non
      pneumatic anti-shock garment for resuscitation and haemostasis following
      obstetric haemorrhage resulting in severe shock. DESIGN: During a six-week
      period, the author served a locum tenens as the obstetrician consultant for the
      Memorial Christian Hospital, Sialkot, Pakistan. All women who suffered from
      severe obstetric haemorrhage were managed with the anti-shock garment as the
      first intervention. The data for this report were collected from hospital chart
      review. SETTING: Sialkot is a city of about three million and Memorial Christian
      Hospital is one of two major obstetric hospitals. There is no blood bank at
      Memorial Christian Hospital or elsewhere in Sialkot. The Memorial Christian
      Hospital laboratory is able to draw donor blood, type and cross match blood, and
      process it for transfusion 24 hours per day. POPULATION: During the six weeks of
      this study, in June and July 2001, there were 764 deliveries and 34 other
      admissions within a week following deliveries outside the hospital. Seven women
      with obstetric haemorrhage who developed severe shock were managed with the anti
      shock garment. One woman, who was later found to have mitral stenosis, developed
      dyspnea upon placement of the anti-shock garment and therefore it was removed
      within 5 minutes. This report concerns the six women who were able to tolerate
      the anti-shock garment without untoward symptoms. METHODS: As soon as severe
      shock was recognised in the hospital, the anti-shock garment was placed.
      Crystalloid solutions were given intravenously over the first hour at a rate of
      1500 mL per estimated litre of blood loss, then at a maintenance rate of 150
      mL/hour. Vital signs every 15 to 30 minutes, hourly urine output and intermittent
      oxygen saturation were used to monitor patients during the use of the anti-shock
      garment. When sufficient blood transfusion had been given to restore the
      haemoglobin to >7 g/dL, the anti-shock garment was removed in segments at 15
      minute intervals with documentation of vital signs before removal of each
      subsequent portion. MAIN OUTCOME MEASURES: Restoration of mean arterial pressure
      of 70 mmHg and clearing of sensorium were considered as signs of effective
      resuscitation. Haemorrhage was considered controlled if the blood loss was less
      than 25 mL/hour. Morbidity included any complications noted in the medical chart.
      RESULTS: Restoration of blood pressure and improvement of mental status occurred
      within 5 minutes in two patients who were pulseless and three who were
      unconscious or confused. All patients had improvement of mean arterial pressure
      to greater than 70 mmHg within 5 minutes. Duration of anti-shock garment use
      ranged from 12 to 36 hours and none of the six women had significant further
      bleeding while the anti-shock garment was in place. Patients were comfortable
      during use of the anti-shock garment and no adverse effects were noted apart from
      a transient decrease in urine output. CONCLUSIONS: The anti-shock garment rapidly
      restored vital signs in women with severe obstetric shock. There was no further
      haemorrhage during or after anti-shock garment use and the women experienced no
      subsequent morbidity. A prospective randomised study of the anti-shock garment
      for management of obstetric haemorrhage is needed to further document these
      observations.

PMID- 12504975
TI  - The management of symptomatic hydronephrosis in pregnancy.
AB  - OBJECTIVE: To present and to evaluate the conservative and surgical management of
      hydronephrosis in pregnancy. DESIGN: Retrospective analysis of an interventional
      cohort. SETTING: A tertiary maternity ward. SAMPLE: Of the 30,552 women
      delivering in our institution between January 1998 and June 2001, 56 women (0.2%)
      were admitted to the prenatal care unit due to symptomatic hydronephrosis.
      METHODS: For each patient, renal sonography, urinalysis, serum creatinine levels,
      white blood cell counts and urine culture were obtained. All patients were
      treated conservatively by analgesics, intravenous fluids and antibiotics. Failure
      of these measures: non-resolving infection, deteriorating renal function, absence
      of Doppler sonographic evidence of ureteral flow or intractable pain led to
      instrumental drainage of the affected kidney. A double pigtail polyurethane
      ureteric stent was passed under cystoscopic vision and sonographic guidance. MAIN
      OUTCOME MEASURES: Resolution of clinical symptoms. RESULTS: Conservative
      treatment led to resolution in 52 women (92.9%), whereas four women (7.1%) failed
      to respond and were treated successfully and without complications by pigtail
      insertion. Early induction of labour was unnecessary and good perinatal outcome
      was the rule. CONCLUSIONS: Although the vast majority of cases of symptomatic
      hydronephrosis in pregnancy may be treated conservatively, pigtail insertion is
      an efficient and safe modality for the rare patient with refractory symptoms.

PMID- 12504976
TI  - Prenatal diagnosis of bilateral isolated fetal hyperechogenic kidneys. Is it
      possible to predict long term outcome?
AB  - OBJECTIVE: To study perinatal and long term outcome following prenatal diagnosis
      of hyperechogenic kidneys. DESIGN: Prospective observational cohort study.
      SETTING: The Maternite Port-Royal Hopital Cochin and at the Departments of
      Obstetrics and Paediatric Nephrology, Necker Enfants Malades in Paris, France.
      POPULATION: Forty-three fetuses with isolated bilateral hyperechogenic kidneys.
      METHODS: All patients referred with isolated bilateral hyperechogenic fetal
      kidneys were followed up prospectively up to 34-132 months. The following
      prenatal items were analysed: fetal kidney size, amniotic fluid volume,
      gestational age at diagnosis, family history and renal ultrasound in parents.
      Postmortem examination was carried out in cases with perinatal death. Postnatal
      follow up of survivors included postnatal ultrasound, blood pressure, serum
      creatinine, proteinuria, need for restricted diet, weight and height and renal
      biopsy when available. MAIN OUTCOME MEASURES: Aetiology of hyperechogenicity,
      perinatal mortality and renal function in survivors. RESULTS: The aetiology could
      be established by family history, postmortem or postnatal data, but not by
      prenatal ultrasound. There were 20 autosomal recessive, 8 autosomal dominant
      polycystic kidney diseases, 9 other renal disorders and 6 symptom-free survivors
      without aetiological diagnosis. There were 19 terminations of pregnancy, 5
      neonatal deaths and 19 survivors, of whom 14 had normal renal function three had
      mild and two had end stage renal failure. None of those with severe
      oligohydramnios and fetal kidneys > 4 SD survived (n = 14, 10 terminations and 4
      neonatal deaths), whereas of the 17 with normal amniotic fluid volume and kidneys
      < 4 SD, 14 survived, of whom 9 were symptom-free. CONCLUSION: Aetiology could not
      be established prenatally in the absence of familial data. Kidney size and
      amniotic fluid volume were the best prenatal predictors of outcome.

PMID- 12504977
TI  - Olfactory modulation of nausea during early pregnancy?
AB  - OBJECTIVES: To investigate whether nausea and vomiting and olfactory sensitivity
      are correlated, we determined whether subjects with little or no nausea and
      vomiting are less sensitive to odours than subjects who indicate a high degree of
      nausea and vomiting, and whether subjects with relatively low olfactory
      sensitivity are less prone to nausea and vomiting than subjects with relatively
      higher olfactory sensitivity. DESIGN: Cross sectional study. SETTING: The Unit of
      Perinatal Physiology, Department of Obstetrics, University Hospital, Zurich,
      Switzerland. POPULATION: Fifty-three women in early pregnancy. METHODS: Following
      a detailed history related to olfaction and nausea and vomiting, subjects filled
      in a nausea profile which provided a 'general nausea score' comprised of the
      factors 'somatic distress', 'gastrointestinal distress', and 'emotional
      distress'. Olfactory function was assessed using pen-like odour dispensing
      devices ('sniffin' sticks'). Tests included n-butanol odour threshold, odour
      discrimination and odour identification. MAIN OUTCOME MEASURES: Olfactory
      function assessed by means of the sniffing sticks nausea profile. RESULTS:
      Correlational analyses between results of olfactory sensitivity and scores from
      the nausea questionnaire were not significant. Further, when subjects were
      divided into groups with relatively low or relatively high overall scores in the
      nausea profile, olfactory sensitivity did not differ between groups. Similarly,
      other analyses did not indicate a modulation of nausea and vomiting through
      olfactory sensitivity. CONCLUSIONS: These findings do not support the hypothesis
      that higher olfactory sensitivity relates to an increase of nausea. However, they
      do support the idea that olfactory-induced nausea is independent of subjectively
      perceived intensity. Olfactory-induced nausea appears to be due to the cognitive
      processing of olfactory information which, in early pregnancy, is reported to be
      altered in an unsystematic fashion.

PMID- 12504978
TI  - Lay perceptions of a 'natural' menopause. Cross sectional study of the British
      Women's Heart and Health Study.
AB  - Health practitioners and researchers define a natural menopause as one not due to
      a hysterectomy or oophorectomy. In a large cross sectional study of
      postmenopausal women, we found that the majority of women who report that their
      menopause was not natural gave a gynaecologic reason. However, 3% gave a major
      life event, such as divorce or bereavement. Age at menopause for women who had
      had a hysterectomy/oophorectomy was the same as that of women who reported that
      their periods has stopped because of a major life event-on average six years
      younger than that of women who described their menopause as natural. We suggest
      that women whose periods stop 'naturally' (from a medical perspective) but at a
      relatively young age perceive this as unnatural and search for an explanation for
      the early cessation of their menses.

PMID- 12504979
TI  - Adnexectomy for benign pathology at vaginal hysterectomy without laparoscopic
      assistance.
AB  - Of 166 consecutive women with a benign adnexal mass scheduled for vaginal
      hysterectomy with adnexectomy, the operation was successful in 158 (95%).
      Preoperatively, attempts were made to ascertain that adnexal mass was benign and
      either freely mobile or with only slightly restricted mobility. Laparotomy was
      required in eight women, in five for adhesions and in three for malignancy
      detected during the operation. No woman required laparoscopic-assisted surgery.
      The 158 women who had successful vaginal hysterectomy with adnexectomy were
      compared with 100 similar women who had a laparotomy performed by same single
      operator. The vaginal group had a lower morbidity, speedier recovery and shorter
      hospital stay.

PMID- 12504980
TI  - Direct current cardioversion during pregnancy should be performed with facilities
      available for fetal monitoring and emergency caesarean section.

PMID- 12504981
TI  - Vesicocervical fistula following insertion of a modified McDonald suture.

PMID- 12504982
TI  - Successful microwave ablation of endometrial carcinoma.

PMID- 12504983
TI  - Incidental diagnosis of primary fallopian tube carcinoma during prophylactic
      salpingo-oophorectomy in BRCA2 mutation carrier.

PMID- 12504984
TI  - Argon beam coagulation during caesarean section.

PMID- 12504985
TI  - Guidelines on using guidelines.

PMID- 12504986
TI  - Routine induction of labour at 41 weeks of gestation: nonsensus consensus.

PMID- 12504987
TI  - In praise of Kielland's forceps.

PMID- 12504988
TI  - A revolution in cervical screening.

PMID- 12504989
TI  - The denominator for maternal mortality--total births or live births?

PMID- 12504990
TI  - The sharp end of medical practice: the use of acupuncture in obstetrics and
      gynaecology.

PMID- 12504991
TI  - The sharp end of medical practice: the use of acupuncture in obstetrics and
      gynecology.

PMID- 12504992
TI  - The ORACLE I and II randomised trial results do not remove the need for
      prophylaxis against early onset Group B streptococcal disease.

PMID- 12504993
TI  - Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and
      intrauterine growth retardation in women with bilateral uterine artery notches.

PMID- 12504994
TI  - Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and
      intrauterine growth retardation in women with bilateral uterine artery notches.

PMID- 12504995
TI  - A randomised controlled trial of antibiotic prophylaxis in elective caesarean
      delivery.

PMID- 12504996
TI  - Can ultrasound replace ambulatory urodynamics when investigating women with
      irritative urinary symptoms?

PMID- 12504997
TI  - A randomised controlled trial of antibiotic prophylaxis in elective caesarean
      delivery.

PMID- 12504998
TI  - Effect of twin-to-twin delivery interval on umbilical cord blood gas in the
      second twins.

PMID- 12504999
TI  - Herbal medicinal products during pregnancy: are they safe?

PMID- 12505000
TI  - Early onset discordant growth in a successful monochorionic twin pregnancy.

PMID- 12505001
TI  - Inconsistent detection of interleukin-10 in the maternal serum.

PMID- 12505002
TI  - Non-surgical treatment of uterovaginal prolapse using double vaginal rings.

PMID- 12505003
TI  - A randomised comparison and economic evaluation in laparoscopic assisted
      hysterectomy and abdominal hysterectomy.

PMID- 12505004
TI  - A randomised comparison and economic evaluation of laparoscopic-assisted
      hysterectomy and abdominal hysterectomy.

PMID- 12505005
TI  - A randomised comparison and economic evaluation in laparoscopic assisted
      hysterectomy and abdominal hysterectomy.

PMID- 12505006
TI  - A randomised comparison and economic evaluation of laparoscopic-assisted
      hysterectomy and abdominal hysterectomy.

PMID- 12505007
TI  - Are there common triggers of preterm deliveries?

PMID- 12505009
TI  - To ban or not to ban?

PMID- 12505011
TI  - Tackling AIDS and sufferings in Africa.

PMID- 12505012
TI  - New technology identifies bacteria in space.

PMID- 12505014
TI  - Tsetse eradication programme under fire.

PMID- 12505015
TI  - Preventing malaria in pregnancy.

PMID- 12505021
TI  - Chilean research throws light on hantavirus transmission.

PMID- 12505023
TI  - West Nile poliomyelitis.

PMID- 12505024
TI  - Predicting the transmission of drug-resistant HIV: comparing theory with data.

PMID- 12505025
TI  - The Black Death and DNA.

PMID- 12505026
TI  - Concomitant bilateral herpes zoster ophthalmicus.

PMID- 12505027
TI  - Beauty and the beast.

PMID- 12505028
TI  - The effect of drug resistance on the fitness of Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis remains a leading infectious cause of morbidity and
      mortality. While antibiotic resistance is cited as a potential threat to efforts
      aimed at controlling the spread of this pathogen, it is not clear how drug
      resistance affects disease dynamics. The effect of mutational events that lead to
      antibiotic-resistant phenotypes may or may not have a predictable effect on the
      fitness of drug-resistant tuberculosis strains. Here, we review the literature on
      laboratory studies of the fitness of drug-resistant tuberculosis, we examine the
      evidence from cluster studies, and we consider the effect of drug resistance on
      disease dynamics in mathematical models. On the basis of these diverse lines of
      evidence, we conclude that the fitness estimates of drug-resistant M tuberculosis
      are quite heterogeneous and that this variation may preclude our ability to
      predict future trends of this pathogen.

PMID- 12505030
TI  - Mutation rate and the efficacy of antimicrobial drug treatment.
AB  - Despite rapid progress in drug development, microbial infections in general are
      becoming increasingly difficult to treat as a result of the emergence of drug
      resistant strains. In some cases, such as HIV-1, the early goal of eradicating
      infections with antimicrobial drugs is, for now, being replaced with the more
      pragmatic goal of controlling infections over long periods of time through a
      succession of transiently effective treatments. Because treatment efficacy is
      often incomplete, studying the degree of treatment efficacy has great relevance
      to clinical disease management. We derived a model describing the association
      between the mutation rate of the pathogen and the degree of treatment efficacy.
      We found that drug treatment is most effective when the mutation rate of the
      pathogen is either very low or, perhaps counterintuitively, very high. We discuss
      this finding in the light of a promising new treatment strategy for RNA viruses
      that combines antiviral compounds with a mutagen.

PMID- 12505029
TI  - Travel and the spread of HIV-1 genetic variants.
AB  - HIV-1 comprises three groups, the main (M group), O (outlier) and N (non-M, non
      O). The M group, divided into 11 subtypes, is responsible for the global HIV-1
      pandemic. Recombination between M subtypes has resulted in the generation of
      multiple circulating recombinant forms (CRFs) consisting of mosaic lineages. Most
      subtypes and CRFs are represented in Africa, whereas predominance of one or a few
      subtypes was reported initially elsewhere. This finding reflects the African
      origin of the epidemic. In western countries, where the B subtype is predominant,
      there is a steep increase in non B-subtypes and CRFs, while new recombinants
      emerge worldwide. Travellers contribute to the spread of HIV-1 genetic diversity
      worldwide, and in the developing world migration of rural populations and civil
      war are additional contributing factors. The spreading of HIV-1 variants has
      implications for diagnostic, treatment, and vaccine development.

PMID- 12505031
TI  - Diphyllobothriasis.

PMID- 12505032
TI  - Is clinical outcome of dengue-virus infections influenced by coagulation and
      fibrinolysis? A critical review of the evidence.
AB  - Despite efforts to elucidate the pathogenesis of dengue fever, the progression
      into severe disease remains poorly understood. In-vitro findings suggest that
      coagulopathy and disturbances in fibrinolysis have a pivotal role in the
      pathophysiology. If disturbances in these processes are predictive of clinical
      outcome in this disease, there could be important consequences for both diagnosis
      and treatment. We have critically reviewed publications on this topic to assess
      whether there is an association between activation of coagulation and
      fibrinolysis and clinical outcome of dengue-virus infections. In general, the
      selected studies showed activation of both the coagulation and fibrinolytic
      systems in this infection. The activation was more pronounced in severe
      infections and in cases with a poor clinical outcome. However, the findings were
      not consistent, and owing to a lack of detailed information on characteristics of
      patients, disease, and study design, we could not ascertain whether
      inconsistencies were caused by differences in these characteristics, selection
      bias, or confounding factors. We conclude that an association between activation
      of coagulation and fibrinolysis and clinical outcome of dengue-virus infections
      is conceivable but has been inadequately assessed and that methodologically sound
      studies, complemented with complete and reliable reporting, are needed to show
      whether there is a true association.

PMID- 12505033
TI  - Lessons learned from the emergence of a new Trypanosoma brucei rhodesiense
      sleeping sickness focus in Uganda.
AB  - During the latter months of 1998, cases of sleeping sickness caused by
      Trypanosoma brucei rhodesiense presented in Soroti district, eastern Uganda, a
      region which had not previously experienced cases of the disease. Cattle are the
      main reservoir for T b rhodesiense, by contrast with sleeping sickness caused by
      Trypanosoma brucei gambiense in west Africa where there appears to be no
      epidemiologically significant animal reservoir. Several factors have been
      identified that interacted to produce ideal conditions for the establishment of a
      new disease focus. After a period of civil unrest, Soroti, which is within the
      tsetse belt, was repopulated by people and later, cattle. Both the cattle
      restocking and the subsequent trade in these cattle at a local cattle market had
      a role in the appearance of the disease. Recently, molecular biology techniques
      have become available for the detection and genotype identification of T b
      rhodesiense and thus it is now possible to distinguish human infective and non
      infective trypanosomes in cattle. In light of these advances in identification
      and in both field and epidemiological techniques, successful disease control
      management has become an achievable goal and will require the collaboration and
      expertise of clinicians, veterinarians, epidemiologists and laboratory
      scientists.

PMID- 12505035
TI  - Antibiotic resistance--the interplay between antibiotic use in animals and human
      beings.

PMID- 12505036
TI  - Richard Greenberg--infectious disease specialist at the University of Kentucky
      Chandler Medical Center interviewed by Pam Das.

PMID- 12505040
TI  - Forgotten heroes.

PMID- 12505041
TI  - Longitudinal impedance is independent of outflow resistance.
AB  - BACKGROUND: Many investigators have measured outflow resistance (R) following
      peripheral bypass procedures, but correlations with graft patency have been weak.
      This is because the primary determinants of graft patency are the size and
      quality of the conduit, not its outflow bed. Efforts at separating conduit
      resistance from outflow resistance have been unsuccessful. Recently, the concept
      of longitudinal impedance ( integral Z(L)) has been suggested as a measure of
      conduit resistance independent of outflow resistance. The purpose of this in
      vitro experiment was to test the hypothesis that integral Z(L) is independent of
      R within physiologically relevant ranges. METHODS: Rigid polyethylene tubing of
      known internal diameter and length (4.3 mm, 375 cm) was perfused with a
      glycerin/saline mixture mimicking the viscosity of blood (4.1 cp), utilizing a
      variable pulsatile pump and Windkessel, with outflow into multiply branched tubes
      of decreasing diameter simulating the hemodynamic conditions of arterial bypass.
      Flow and pressure were measured using ultrasonic transit time and catheter
      transduction, respectively, and waveforms digitized at 200 Hz. Flow was varied
      while maintaining "systemic" pressure and resistance. After Fourier
      transformation, integral Z(L) was calculated as deltaP/Q at each harmonic and
      integrated over 4 Hz. RESULTS: integral Z(L) calculations were remarkably
      reproducible within the same day with a coefficient of variation (CV) = 4.0% (at
      100 dyne. s/cm(5); n = 4) or over 4 successive days (CV = 4.3%). Furthermore,
      integral Z(L) was largely independent of R over the physiologic range tested,
      with integral Z(L) remaining relatively constant as R was increased sixfold.
      CONCLUSION: integral Z(L) is a consistent and reproducible measure of conduit
      resistance independent of R over a wide physiologic range. It may be useful for
      measuring the adequacy of bypass graft conduits.

PMID- 12505042
TI  - Differential mechanical activation of mitogen-activated protein kinases in intact
      human blood vessels.
AB  - BACKGROUND: Vascular tissue remodels in response to a variety of hemodynamic
      factors, often transduced through activation of mitogen-activated protein kinases
      such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase
      (JNK). This study tests the hypothesis that these kinases are involved in
      mechanical signal transduction in intact human arteries and veins. METHODS:
      Unused portions of human saphenous vein and radial artery were obtained fresh at
      the time of peripheral or coronary bypass. A sample of the vessel was immediately
      snap frozen (control(0)) and the remainder separated into three segments. One
      segment was placed in sterile medium and left undisturbed for 2 h (control(2)),
      one was perfused with sterile medium for 2 h at a steady rate of 150 ml/min,
      yielding shear stress values of 8-20 dyne/cm(2) (flow), and one was statically
      pressurized without flow at 110 mm Hg for 2 h (pressure). After treatment,
      samples were tested for phosphorylated ERK1/2 and JNK using Western blot.
      RESULTS: Two hours of culture produced mild increases in ERK1/2 activity in both
      vessel types. Stimulation with continuous rapid flow produced significantly
      increased ERK1 activity and a nearly 100% increase in ERK2 in veins. Static
      pressurization also stimulated ERK1/2, although slightly less than continuous
      flow. ERK1/2 phosphorylation was only mildly increased in flow-stimulated radial
      arteries, and exposure to normal systemic pressure showed no appreciable effect.
      Significant phosphorylation of JNK was not observed in either vessel. CONCLUSION:
      ERK1/2 phosphorylation is increased in human saphenous veins and radial arteries
      exposed to the hemodynamic conditions of arterial grafting. This pathway may be
      involved in the transduction of external stimuli leading to remodeling.

PMID- 12505043
TI  - Mesenchymal nuclear transcription factors in nitrofen-induced hypoplastic lung.
AB  - BACKGROUND: Nitrofen-induced pulmonary hypoplasia (PH) with or without coexistent
      congenital diaphragmatic hernia (CDH) in animals mimics the human condition. We
      have demonstrated reduced steroid-thyroid-retinoid receptors in hypoplastic
      lungs. Therefore, we hypothesize that expression of two additional mesenchymally
      derived nuclear transcription factors, retinoid X receptor alpha (RXR-alpha) and
      homeobox b-5 (Hoxb-5), would also be altered in hypoplastic lungs. MATERIALS AND
      METHODS: We used timed-pregnant CD-1 mice either untreated or gavaged with
      nitrofen on gestational day (Gd) 8. Normal lungs were compared with hypoplastic
      lungs with severe left PH and CDH at Gd 14, 16, and 19 and from neonates. We
      performed immunoblotting for RXR-alpha and Hoxb-5 proteins and
      immunohistochemistry for Hoxb-5 protein. RESULTS: Almost 70-80% of nitrofen
      exposed mice had no apparent external phenotypic abnormalities, such as
      craniofacial defects. Fetal body and lung weights were reduced. RXR-alpha and
      Hoxb-5 proteins were highest at Gd 14 and decreased as development progressed.
      Densitometric analysis of RXR-alpha or Hoxb-5 proteins in normal and hypoplastic
      lungs showed no significant difference; however, the immunolocalization pattern
      of Hoxb-5 protein differed. Hoxb-5 protein was primarily in mesenchymal cells of
      normal lungs on Gd 14; however, by Gd 19, it appeared to be mainly in the
      epithelial cells of prealveolar structures and in adjacent subepithelial
      mesenchymal cells. In hypoplastic lungs no significant changes were observed in
      Hoxb-5 staining in mesenchymal cells at Gd 14 nor at Gd 16; however, Hoxb-5
      expression persisted in mesenchyme and epithelium at Gd 19 and in neonatal
      hypoplastic lungs, unlike normal lungs. CONCLUSIONS: (1) Unaltered RXR-alpha
      protein implies that despite altered retinoic acid receptors (RARs) in
      hypoplastic lungs, the mechanisms of nitrofen-induced PH may be independent of
      RXR-alpha pathways. (2) In hypoplastic lungs, the persistent mesenchymal
      expression of Hoxb-5, in later stages of development and at birth, suggests
      delayed development and maturation compared to normal lungs. We speculate that
      nitrofen induces PH via RAR-dependent but RXR-independent interactions, which may
      be downstream of the Hoxb-5 gene or may involve other more anteriorly expressed
      Hox genes.

PMID- 12505044
TI  - Selectins influence thrombosis in a mouse model of experimental deep venous
      thrombosis.
AB  - BACKGROUND: This study characterizes venous thrombosis in the mouse and examines
      the important role that the adhesion molecules P-selectin and E-selectin and the
      anti-inflammatory cytokine interleukin-10 (IL-10) play in the thrombotic process.
      MATERIALS AND METHODS: C57BL/6 (wild-type) mice in a natural history protocol
      (Phase I) and gene-targeted (KO) mice for P-selectin, E-selectin, P/E-selectin,
      and IL-10 in a follow-up protocol (Phase II) were studied. Inferior vena caval
      thrombosis was produced by ligation just below the renal veins, and mice were
      sacrificed and evaluated at various time points up to 12 days later. RESULTS:
      Phase I: A significant increase in neutrophils on day 2 and in monocytes on day 6
      postthrombosis was found in ligated vs sham animals. An associated significant
      increase in vein wall P-selectin mRNA (6 h, day 2) and an increase in protein (6
      h through day 6) were found, while E-selectin mRNA was significantly increased
      (day 2 through day 6), with a smaller increase in E-selectin protein. IL-10 mRNA
      increased significantly later (day 2 through day 9), with the values increasing
      progressively. A positive correlation existed (r = 0.77) between neutrophils and
      thrombosis at day 2. PHASE II: The E-selectin and P/E-selectin double-KO mice
      showed the least thrombus at day 2 vs wild-type clotted mice, P < 0.01.
      Additionally, P/E-KO mice demonstrated the lowest inflammatory cell extravasation
      into the vein wall at day 2. CONCLUSIONS: This study demonstrates an acute to
      chronic inflammatory response in the vein wall associated with venous thrombosis.
      Inhibition of selectins decreased thrombus formation.

PMID- 12505045
TI  - Factors associated with mortality in patients with penetrating abdominal vascular
      trauma.
AB  - OBJECTIVE: Prehospital transport, resuscitation, and operative intervention are
      all critical to the care of the penetrating trauma victim. We determined which
      factors most affected mortality in patients with penetrating abdominal vascular
      injuries. METHODS: Consecutive patients with penetrating abdominal vascular
      injuries from an urban Level I trauma center from January 1993 to December 1998
      were identified from the trauma registry and their charts reviewed. All patients
      who died prior to operative intervention were excluded. Data collected included
      mortality, age, scene time (ST), EMS transport time (TT), time in the emergency
      department (ED), initial systolic blood pressure in the ED (BP), operating time,
      intraoperative estimated blood loss (EBL), and worst base deficit in the first 24
      h (BD). These variables were compared between nonsurvivors and survivors by
      univariate ANOVA. Multivariate ANOVA (MANOVA) determined independent effects on
      mortality. RESULTS: Forty-six penetrating abdominal vascular injuries were
      identified in 31 patients, 11 of whom died (38.7%). Examining prehospital
      parameters, mean ST averaged 16.5 +/- 3.6 min, while TT was 31.8 +/- 7.1 min. For
      ED parameters, initial BP was 94.8 +/- 6.4 mm Hg and initial heart rate was 109
      +/- 7 beats per minute. Mean operative EBL for all patients was 3518 +/- 433 ml.
      The mean BD for all patients was -12.9 +/- 1.8. Significant differences were
      noted in the univariate analysis between survivors and nonsurvivors for BD (P <
      0.0001), BP (P = 0.0062) and EBL (P = 0.0002). MANOVA revealed that only base
      deficit (P < 0.0001) had an independent effect on mortality. CONCLUSIONS: In
      patients with penetrating abdominal vascular injuries who survive their ED stay,
      adverse physiologic parameters reflecting the adequacy of resuscitation are more
      predictive of mortality than identifiable prehospital parameters.

PMID- 12505046
TI  - How surgeon age affects surveillance strategies for extremity soft tissue sarcoma
      patients after potentially curative treatment.
AB  - BACKGROUND: The optimal strategy for follow-up of extremity soft tissue sarcoma
      patients after potentially curative treatment remains unknown. We investigated
      whether the date of completion of formal surgical training affects choice of
      surveillance strategy. MATERIALS AND METHODS: The 1,592 members of the Society of
      Surgical Oncology were asked how often they use 12 separate surveillance
      modalities during years 1-5 and 10 postsurgery. The motivation underlying follow
      up was assessed separately. Repeated-measures analysis of variance was used to
      compare practice patterns by the year in which the surgeon's formal surgery
      training was completed, controlling for tumor grade, tumor size, and year
      postsurgery. RESULTS: Of the 716 respondents, 318 performed surgery and also
      provided long-term postoperative surveillance for their patients. These
      respondents were considered evaluable. Erythrocyte sedimentation rate, extremity
      X ray, and bone scan were the follow-up tests which differed significantly among
      physician age groups. Surgeons who completed training more than 30 years ago
      ordered erythrocyte sedimentation rate more frequently (P < 0.001). Surgeons in
      the 21-30 year category ordered extremity X ray and bone scan more frequently (P
      < 0.05), but the absolute differences among age groups were quite small. Older
      surgeons were also significantly more likely to believe that follow-up is
      clinically worthwhile. CONCLUSIONS: The posttreatment surveillance practice
      patterns of the members of the Society of Surgical Oncology caring for extremity
      soft tissue sarcoma patients vary only marginally with the length of time since
      completion of training. Postgraduate education may be one factor homogenizing
      surgeon behavior in this important aspect of cancer patient care.

PMID- 12505047
TI  - Effect of transforming growth factor-alpha on intestinal adaptation in a rat
      model of short bowel syndrome.
AB  - OBJECTIVE: TGF-alpha has recently been shown to stimulate enterocyte
      proliferation. In the present study we investigated the effect of TGF-alpha on
      enterocyte proliferation and loss via apoptosis and its effects on intestinal
      adaptation in a rat following massive bowel resection. METHODS: Male Sprague
      Dawley rats underwent bowel transection and reanastomosis (sham group) or 75%
      small bowel resection and anastomosis (SBS group) and were treated with
      intraperitoneal TGF-alpha (75 microg/kg) from the ninth postoperative day (SBS
      TGF-alpha group). Parameters of intestinal adaptation (overall bowel and mucosal
      weight, mucosal DNA and protein, villus height, and crypt depth), enterocyte
      proliferation, and apoptosis were determined on day 15. Statistical significance
      was determined by ANOVA with a P < 0.05 considered significant. RESULTS: SBS-TGF
      alpha rats demonstrated a significant increase (vs SBS) in duodenal, jejunal, and
      ileal overall bowel and mucosal weights; ileal mucosal DNA and protein; and
      jejunal and ileal villus height. SBS-TGF-alpha rats also showed an increased cell
      proliferation index in jejunum (704 +/- 43 vs 499 +/- 63 BrdU-positive cells/10
      crypts, P < 0.05) and ileum (715 +/- 84 vs 529 +/- 40 BrdU-positive cells/10
      crypts, P < 0.05) and decreased apoptotic index in ileum (8.7 +/- 1.1 vs 21.8 +/-
      3.2 apoptotic cells/1,000 villus cells, P < 0.05) compared to SBS animals.
      CONCLUSIONS: In a rat model of SBS, TGF-alpha enhances intestinal adaptation.
      Possible mechanisms may include increased cell proliferation and decreased
      enterocyte loss via apoptosis.

PMID- 12505048
TI  - Delayed differentiation of HL-60 cells following exposure to hypoxia.
AB  - OBJECTIVE: Hemorrhagic shock and hypoxia have been shown to alter immune and
      hematopoietic functions. Cellular hypoxia is thought to be the primary defect and
      has been shown to induce a variety of biological alterations. In this study, we
      examined if this defect is at the stage of terminal differentiation with the
      myelomonocytic cell line HL-60. METHODS: After hypoxia, HL-60 cells were induced
      with 1.25% dimethyl sulfoxide (DMSO) to differentiate toward neutrophils (PMN).
      The ability to differentiate was evaluated by nitroblue tetrazolium staining. The
      function of the differentiated cells was determined by intracellular calcium
      levels after exposure to different chemotactic factors, and levels of Id-2 mRNA,
      a factor associated with terminal differentiation of myeloid cells, were assessed
      with Northern analysis. RESULTS: At 48 h following exposure to hypoxia, HL-60
      differentiation was significantly blunted (hypoxia 51 +/- 1%, normoxia 69 +/- 1%;
      P < 0.001). Intracellular calcium levels in DMSO-treated cells stimulated with 1
      microM bacterial tripeptide, fMLP, were significantly reduced in the hypoxic
      cells (381 +/- 11 nM vs 449 +/- 10 nM; P < 0.01). No difference was noted for two
      other chemotactic factors, C5a and platelet-activating factor. Using Northern
      analysis to determine the levels of Id-2 mRNA, we demonstrated that hypoxia
      reduced the levels by 20% over normoxic cells. CONCLUSION: This study
      demonstrates that hypoxia blunts the differentiation of HL-60 cells to PMN. This
      altered function of hypoxia appears to be reversible since hypoxia prolonged the
      time for HL-60 cells to differentiate and this may be partly explained by the
      premature downregulation of Id-2 expression.

PMID- 12505049
TI  - Increased intraabdominal pressure impairs liver regeneration after partial
      hepatectomy in rats.
AB  - BACKGROUND: There are many experimental studies showing that increased
      intraabdominal pressure (IAP) reduces liver blood flow, leading to ischemia and
      portal venous congestion. But, there is no study evaluating the effect of
      increased IAP on liver regeneration. It is well known that acute liver ischemia
      and portal venous congestion impair liver regeneration. We, therefore, aimed to
      determine the effect of increased IAP on liver regeneration in this study.
      METHODS: Sprague-Dawley rats underwent partial hepatectomy with or without IAP of
      12-14 mm Hg for 24 h or sham operation. Rats were randomly divided into six
      groups: two sham-operated groups, two hepatectomy groups, and two hepatectomy
      with increased IAP groups. Mitotic index, proliferating cell nuclear antigen
      (PCNA)-labeling index, and liver regeneration rate as liver regeneration
      parameters were studied on day 1 or on day 4 after operation. Additionally, serum
      aspartate transaminase (AST) level and histopathological changes in intestinal
      mucosa were studied. RESULTS: Hepatectomy with/without increased IAP groups had
      significantly higher serum AST levels than the sham-operated group on day 1.
      Serum AST level was found to be significantly higher in the hepatectomy with
      increased IAP group than in the other groups on day 4. Intestinal mucosal injury
      was found in the hepatectomy with increased IAP groups on days 1 and 4. Mitotic
      index and PCNA-labeling index were markedly higher in all hepatectomy
      with/without increased IAP groups than in the sham-operated groups. However,
      together with liver regeneration rate, both indices were significantly less in
      the hepatectomy with increased IAP groups than in the hepatectomy groups both on
      day 1 and on day 4. CONCLUSION: Maintenance of IAP between 12 and 14 mm Hg for 24
      h impaired liver regeneration after partial hepatectomy in rats.

PMID- 12505050
TI  - Vascular growth factor expression in a rat model of severe limb ischemia.
AB  - BACKGROUND: In ischemic tissue hypoxia induces production of vascular growth
      factors, especially VEGF, which initiate local angiogenesis. Collateralization-or
      arteriogenesis-occurs at a distance from the ischemic tissue and depends on
      different growth factors such as FGF-2. A spatial discrepancy in endogenous
      growth factor production in limb ischemia may have implications for therapeutic
      angiogenesis. The present study elucidates if such spatial and temporal variation
      occurs. MATERIALS AND METHODS: A two-staged procedure was performed to generate
      severe long-lasting limb ischemia in 60 rats. At 1, 7, 28, and 56 days, subgroups
      were subjected to perfusion assessment with laser Doppler imaging and
      angiography. Muscle samples and foot skin were gathered to measure growth factor
      expression and signs of angiogenesis using immunohistochemistry. RESULTS: There
      was an early twofold increase (P < 0.05) in both VEGF and FGF-2 levels in distal
      muscle from the ischemic leg, but no significant rise in the thigh. The
      concentrations decreased over time with an exception for VEGF in soleus and FGF-2
      in anterior tibial muscle, which remained high. An increased capillarity was
      noted (P < 0.05) in soleus after 28 days, and the number of BrdU-positive ECs was
      elevated in all ischemic samples at 56 days. Collateral arteries were observed on
      the angiograms after 7 days. CONCLUSIONS: The results suggest that in limb
      ischemia any major increase in vascular growth factor production is limited to
      ischemic tissue. The spatial and temporal distribution patterns of growth factor
      production are complex and to a great extent influenced by inflammation.

PMID- 12505051
TI  - IL-11 pretreatment reduces cell death after intestinal ischemia-reperfusion.
AB  - BACKGROUND: Intestinal ischemia-reperfusion (IR) injury results in enterocyte
      necrosis and apoptosis. This study was designed to evaluate the potential
      protective effects of interleukin-11 (IL-11) pretreatment on intestinal mucosa
      following IR injury. MATERIALS AND METHODS: Sham (n = 7) and control animals (n =
      7) received 48 h of intravenous saline while treatment animals (n = 7) received
      IL-11 (750 microg/kg/day). Sham animals then underwent laparotomy alone, while
      control and treatment animals underwent 35 min of mesenteric artery occlusion and
      120 min of reperfusion. Midjejunum samples were obtained and serum was drawn.
      Fluorometric assays were performed for hexosaminidase A (HEX A) and beta
      glucuronidase (GLUC), markers of enterocyte necrosis. Apoptosis was quantified by
      TUNEL and confirmed by DNA fragmentation. Transcription of Bcl-2, an
      antiapoptotic regulator, was assessed by multiplex RT-PCR. Statistical analysis
      was performed using ANOVA and expressed as means +/- SEM. RESULTS: In pretreated
      animals, HEX A and GLUC activities after IR were reduced from 570 +/- 54 to 426
      +/- 47 nmol/ml/h (P < 0.05) and from 183 +/- 29 to 125 +/- 7 nmol/ml/h (P <
      0.01), respectively. Pretreated animals had a reduced number of apoptotic cells
      per 10 crypts (79 +/- 11) compared with untreated rats (255 +/- 17) after IR
      injury (P < 0.01). Mucosal DNA from pretreated rats qualitatively showed less
      fragmentation on electrophoresis. Relative Bcl-2 band intensity was higher in
      pretreated animals (1.04 +/- 0.09) compared with controls (0.78 +/- 0.07) (P <
      0.05). CONCLUSIONS: IL-11 pretreatment reduced crypt cell apoptosis after IR
      injury, possibly by upregulating Bcl-2. Treated animals also demonstrated
      attenuation in the release of certain lysosomal enzymes. These data indicate that
      following IR injury, IL-11 improves enterocyte survival by reducing necrosis and
      apoptosis.

PMID- 12505052
TI  - Health-related quality of life and postoperative length of stay for patients with
      colorectal cancer.
AB  - BACKGROUND: Length of stay (LOS) after surgery is a major determinant of resource
      utilization for colorectal cancer (CRC). The purpose of this study was to examine
      the association between pretreatment health-related quality of life (HRQL) scores
      and postoperative hospital LOS in a cohort of patients undergoing surgery for
      CRC. METHODS: Seventy patients with biopsy-proven CRC were enrolled in an IRB
      approved, prospective study. Information was collected concerning standard
      perioperative variables. Prior to surgery, all patients also completed the CRC
      specific module of the Functional Assessment of Cancer Therapy (FACT-C).
      Perioperative variables and FACT-C scores were compared with LOS in both
      univariate and multivariate analysis. LOS for those patients scoring in the
      lowest quartile on FACT-C was compared with LOS for patients scoring in the
      remaining quartiles. RESULTS: Median length of stay for the entire group was 6
      (range 3-25) days. In univariate analysis, surgical complications (10.6 vs 6.6
      days; P = 0.001) and with poorer FACT-C individual scale scores for Physical Well
      Being (9.1 vs 7.3 days; P = 0.04), Functional Well-Being (9.6 vs 7.1 days; P =
      0.006), and Colorectal Cancer Concerns (9.5 vs 7.1 days; P = 0.01) were all
      significantly associated with increased length of stay. In multivariate analysis,
      surgical morbidity (OR = 5.6; 95% CI 1.5-21.4), age >72 (OR = 6.0; 95% CI 1.6
      23.5), and low FACT-C total score (OR = 4.2; 95% CI 1.1-15.6) were independently
      associated with increased LOS. CONCLUSIONS: Pretreatment HRQL scores as measured
      by FACT-C may be of benefit in the prediction of LOS. Such information may be an
      important and currently neglected means of risk-adjusting populations undergoing
      surgery for colorectal cancer for this outcome.

PMID- 12505053
TI  - In vitro anticancer effects of a novel immunostimulant: keyhole limpet
      hemocyanin.
AB  - BACKGROUND: Keyhole limpet hemocyanin (KLH) is a recently described immune
      stimulant and hapten carrier derived from a circulating glycoprotein of the
      marine mollusk Megathura crenulata. It has been reported to be a potent form of
      intravesical immunotherapy for the treatment of transitional cell carcinoma of
      the bladder and has been used in a variety of genitourinary tumors. We
      hypothesized that KLH would be effective against other cancer cells in vitro.
      METHODS: Multiple cancer cell lines were tested, including estrogen-dependent
      breast (MCF-7), estrogen-independent breast (ZR75-1), pancreas (PANC-1, MIA
      PaCa), and prostate (DU145). Serial twofold dilutions of KLH were prepared in
      sterile 96-well plates. Dose-response curves were performed beginning with a
      concentration of 100 microg of KLH/well and ending at a concentration of 0.8
      ng/well. Cells were added at concentrations of 5 x 10(4) cells per well. Cell
      viability was evaluated at 24 and 72 h by MTT assay at an absorbance of 570 nm.
      RESULTS: Significant (P < 0.05) cancer cell growth inhibition was observed in
      four of the five cell lines tested at both time treatment intervals. The breast
      cancer line ZR75-1 exhibited a mean growth inhibition of 43 +/- 1.1% (range 37 to
      59%) at 72 h, whereas treated MCF-7 cells had an average of 39 +/- 9.1% growth
      inhibition (range 35 to 44%) at these same concentrations. Treated PANC-1 cells
      had a mean growth inhibition of 19 +/- 0.8% (range 4 to 46%) at 72 h. The DU145
      prostate cancer cell line averaged a 6 +/- 1.3% growth inhibition (range -19 to
      55%) over the concentrations tested. CONCLUSIONS: The direct growth inhibition of
      multiple tumor cell-lines exhibited by KLH is significant and warrants further in
      vitro mechanistic studies and in vivo experiments. Investigation into the
      efficacy and mechanism of response could directly lead to more effective
      treatment regimens for patients suffering from these diseases.

PMID- 12505054
TI  - Intracellular sorting of renin: cell type specific differences and their
      consequences.
AB  - Renin is commonly known as a secretory glycoprotein, which is expressed, stored
      and released in a regulated manner by the kidney. Besides this, a number of
      extrarenal tissues, such as adrenal gland and heart express or internalise renin.
      In the heart a local RAS may exert prohypertrophic, proliferative,
      antiproliferative or apoptotic properties. The local RAS in kidney, adrenal gland
      and heart are each unique and their modes of action are distinct. This is due to
      the expression of different renin transcripts and different intracellular sorting
      and transport events for renin. In the rat kidney exclusively the commonly known
      preprorenin is expressed encoding for secretory renin. This is targeted to
      lysosomes, which become secretory renin granules. The cells of the rat adrenal
      cortex express preprorenin as well, but this is partially targeted to the
      regulated secretory pathway. Rat adrenocortical cells additionally express an
      alternative renin transcript, termed exon1A renin, which encodes for a truncated
      prorenin that is imported into mitochondria. Its function is not known to date.
      Interestingly, in the rat heart exclusively the alternative transcript is
      expressed. Even in hypertrophic hearts or after myocardial infarction,
      preprorenin remains undetectable. Exon1A renin transcript levels, in contrast,
      markedly increased after myocardial ischemia. This provides a new molecular basis
      for a function of locally expressed renin. In addition, there are different
      pathways of renin internalisation by cardiac cells. A mannose-6-phosphate
      receptor mediated uptake has been described. We recently described another
      pathway independently of the mannose-6-phosphate receptor. Such a pathway is
      apparently of functional significance. Subsequent generation of angiotensins and
      myocyte hypertrophy and proliferation by prorenin through angiotensin generation
      has been described.

PMID- 12505055
TI  - Products of angiotensin I hydrolysis by human cardiac enzymes potentiate
      bradykinin.
AB  - Some beneficial effects of ACE inhibitors are attributed to potentiation of
      bradykinin's actions exerted through its B2 receptor. We investigated them on
      cultured cells transfected or constitutively expressing both ACE and B2 receptor.
      The potentiation of bradykinin was indirect and attributed to a crosstalk induced
      between enzyme and receptor via ACE, a heterodimer formation. While looking for
      endogenous activators, we investigated the split products of angiotensin I (Ang)
      Ang 1-9 and 1-7, peptides released by enzymes of human atria and ventricle. Ang 1
      9 was liberated by a cathepsin A-type enzyme, Ang 1-7 by a different
      metallopeptidase-protease. Cathepsin A's presence in heart tissue was shown by
      deamidating enkephalinamide substrate, by immunoprecipitation and by
      immunohistochemistry. In immunohistochemistry, cathepsin A was detected in
      myocytes of atrial tissue. Ang 1-9 and Ang 1-7 potentiated the effect of an ACE
      resistant bradykinin analogue on the B2 receptor in transfected cells expressing
      human ACE and B2, and in human endothelial cells. Ang 1-9 and 1-7 augmented
      arachidonic acid and NO release by bradykinin. NO liberation by bradykinin from
      endothelial cells was potentiated at 10nmol/L concentration by Ang 1-9 and Ang 1
      7; at higher concentrations, Ang 1-9 was significantly more active. Both peptides
      had little activity in absence of bradykinin or ACE. Ang 1-9 and 1-7 potentiated
      bradykinin action on its B2 receptor at much lower concentrations than their IC50
      values with ACE. They probably induce conformational changes in the ACE/B2
      receptor complex via interaction with ACE.

PMID- 12505056
TI  - Molecular mechanisms of myocardial remodeling. The role of aldosterone.
AB  - Cardiac remodeling, CR, is a complex and rather controversial issue and results
      from the, sometimes opposite, trophic effects of pure mechanical overload, and
      susceptibility factors, as senescence, aetiologies, as ischemia, and the
      neurohormonal reaction. The molecular mechanisms of CR are heritable and had, in
      the past, increased fitness, as such CR belongs to evolutionary medicine.
      Aldosterone production plays an important role in the remodeling of the heart.
      (i) There are numerous evidences that aldosterone induces fibrosis in all the
      cardiovascular system in the presence of high sodium diet. The aldosterone
      receptor is a transcriptional factor and the pathways that lead to aldosterone
      induced fibrosis are multiple. Aldosterone induces the expression of the
      angiotensin II receptors subtype I and that of the glucocorticoid receptors. The
      RALES trial have recently evidenced a significant beneficial effect of
      spironolactone on both mortality and morbidity in heart failure, and a substudy
      has shown that these effects are linked to a reduction is fibrosis. (ii) An
      intracardiac production of aldosterone and corticosterone have been evidenced in
      the rat. Aldosterone production is regulated by low sodium/high potassium diets
      and by angiotensin II and is predominant in atria, cardiac production is low as
      compared to the adrenal production, nevertheless it results in high local
      concentrations, just like angiotensin II. In rats, myocardial infarction
      activates aldosterone production and this activation is prevented by losartan.
      Heart failure, in human, activates aldosterone production and is accompanied by a
      significant increase of the arteriovenous difference in aldosterone by the
      myocardium. To conclude (i) after a myocardial infarction local production of
      aldosterone and angiotensin II are likely to play a major role in regulating
      collagen turnover and fibrous tissue formation; (ii) during heart failure, the
      activation of adrenal and cardiovascular production of aldosterone belongs to the
      neurohormonal reaction and would play a detrimental role in producing reactive
      fibrosis.

PMID- 12505057
TI  - Regulation of myocardial fibrillar collagen by angiotensin II. A role in
      hypertensive heart disease?
AB  - Collagen types I and III (Col I and Col III) are the major fibrillar collagens
      produced by fibroblasts and myofibroblasts in the adult heart. Fibrillar collagen
      of the heart provides the structural scaffolding for cardiomyocytes and coronary
      vessels and imparts cardiac tissue with physical properties that include
      stiffness and resistance to deformation. In addition, fibrillar collagen may also
      act as a link between contractile element of adjacent cardiomyocytes and as a
      conduit of information that is necessary for cell function. As in other organs,
      collagen turnover of normal adult heart results from the equilibrium between the
      synthesis and degradation of Col I and Col III. A number of factors have been
      described that may alter the balance in favor of either the synthesis (e.g.,
      angiotensin II-ANG II-) or the degradation. Predominance of synthesis over
      degradation leads to increased Col I and Col III deposition or fibrosis that
      accompanies cardiac diseases such as hypertensive heart disease. Fibrosis alters
      myocardial structure and function and adversely afects the clinical outcome of
      hypertensive patients. Various lines of evidence suggest that besides
      hypertension, systemically and/or locally produced ANG II may participate in the
      development of hypertensive myocardial fibrosis via activation of ANG II type 1
      receptors (AT(1)R). The potential clinical relevance of this possibility is
      linked to the ability of antihypertensive drugs such as angiotensin converting
      enzyme inhibitors (ACEIs) and AT(1)R antagonists (ARAs) to reverse myocardial
      fibrosis beyond their antihypertensive efficacy.

PMID- 12505058
TI  - Adriamycin-induced cardiomyocyte and endothelial cell apoptosis: in vitro and in
      vivo studies.
AB  - Adriamycin is a potent, broad-spectrum chemotherapeutic agent effective against
      solid tumors and malignant hematological disease. The major limiting factor for
      adriamycin is its cardiotoxicity. Thus, the objective of this study was to
      investigate the role of cardiomyocyte and endothelial cell apoptosis in
      adriamycin-induced cardiomyopathy, in vivo and in vitro. For in vivo study,
      intraperitoneal injections of adriamycin were administered to nine adult male
      Wistar rats and normal saline to six rats as control. Eight of the nine rats in
      the adriamycin group, but none in the control group, developed marked ascites and
      DNA ladders in agarose gel electrophoresis of genomic DNA extracted from the rat
      hearts (P<0.001). The ratio of apoptotic nuclei in the cardiomyocytes was
      significantly higher for the adriamycin-treated rats (162+/-149/10(6) cells) than
      for the controls (4.2+/-1.3/10(6) cells; P<0.01) by TUNEL assay. Increased
      endothelial cell apoptosis was detected in the small coronary vessels of the
      myocardium of the adriamycin-treated rats. Increased immuno-reactive Caspase-3
      expression was also noted for both cardiomyocytes and endothelial cells of
      adriamycin-treated rats. In vitro adriamycin treatment for cultured neonatal rat
      cardiomyocytes and human umbilical vein endothelial cells, respectively, showed a
      dose-related increase in apoptosis as determined by flowcytometry, DNA ladder
      analysis, TUNEL assay and/or electron-microscope examination. A dose-related
      increase in the expression of Fas antigen, Bax and Caspase-3, as well as a
      decrease in the expression of Bcl-2, were determined for the adriamycin-treated
      cardiomyocytes using Northern blot analysis, reverse transcriptase polymerase
      chain reaction (RT-PCR) and ribonuclease protection assay. RT-PCR also revealed
      increased Fas antigen expression, decreased Bcl-2 expression, and no change in
      Bax expression for the adriamycin-treated human umbilical vein cells. Further,
      pretreatment with broad caspase inhibitor, but not neutralizing FasL antibody,
      resulted in inhibition of adriamycin-induced endothelial cell apoptosis. In
      conclusion, these results indicate that both adriamycin-induced cardiomyocyte and
      endothelial cell death can occur via apoptosis which is dose-related, and can
      occur both in vitro and in vivo with changes in the expression of the apoptosis
      related genes. Adriamycin-induced endothelial cell apoptosis is mediated by
      caspase activation but is Fas/FasL signal pathway independent. Our data provides
      evidence that both cardiomyocyte and endothelial cell apoptosis may play an
      important role in adriamycin-induced cardiomyopathy.

PMID- 12505059
TI  - NF-kappaB activation is essential for angiotensin II-dependent proliferation and
      migration of vascular smooth muscle cells.
AB  - Angiotensin II (AngII) functions as a stress hormone under conditions of stretch,
      pressure and injury to stimulate smooth muscle cell migration and proliferation.
      Since the cellular response to stress is mediated in part by the transcription
      factor NF-kappaB, the relationship between AngII and NF-kappaB was investigated.
      Our study revealed that AngII promoted a dose-dependent and transient
      phosphorylation of the regulatory IkappaBalpha protein in smooth muscle cells
      from porcine coronary artery, with concomitant nuclear translocation of NF-kappaB
      and increased binding to a kappaB promoter element. Both nuclear translocation
      and kappaB-element binding were prevented by the AT(1) receptor antagonist
      losartan. The role of NF-kappaB in AngII-dependent smooth muscle cell migration
      and proliferation was then assessed. Inhibitors of NF-kappaB nuclear
      translocation (phenethyl caffeiate) and IkappaB phosphorylation (Bay 11-7085)
      effectively arrested both AngII-dependent DNA synthesis and migration. These
      results were confirmed with SN50, a highly selective peptide inhibitor of NF
      kappaB activation. Phenethyl caffeiate also prevented the phosphorylation of cdk2
      and Rb, indicating NF-kappaB was required for G1/S transition. The target of NF
      kappaB inhibition was identified as cyclin E, since induction of this gene, but
      not cyclin D1, was suppressed by phenethyl caffeiate. We subsequently examined
      the relationship between NF-kappaB and neointimal formation in response to
      angioplasty-induced injury, a process susceptible to inhibition by losartan. Both
      phenethyl caffeiate and Bay 11-7085 blocked neointimal hyperplasia in organ
      culture following balloon angioplasty. These data indicate NF-kappaB is an
      important mediator of intracellular signalling by AngII under normal
      physiological conditions, and following vascular injury.

PMID- 12505060
TI  - Sulfhydryl modulation of K+ channels in rat ventricular myocytes.
AB  - Oxidative stress markedly alters protein function through redox modification of
      sulfhydryl groups present in cysteine residues. To explore the role of redox
      state in modulating cardiac K+ channels, this study examined the effects of
      sulfhydryl modifiers on the repolarizing transient outward current (Ito) in
      voltage-clamped myocytes from rat ventricle. Oxidized glutathione (GSSG; 5mM), an
      endogenous disulfide that specifically reacts with protein sulfhydryls, decreased
      maximum Ito amplitude from baseline by 49% when added to the external solution
      (P<0.05) and by 27% during internal dialysis (P<0.05). The membrane-impermeable
      disulfide, 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) did not alter Ito when
      added to the external solution, but it decreased current amplitude by 31% during
      internal dialysis (P<0.05). GSSG-mediated Ito inhibition varied in a frequency-
      and voltage-dependent manner, consistent with a state-dependent blocking
      mechanism. This phenomenon was also observed in myocytes internally dialyzed with
      DTNB or Cd2+, which also covalently binds to free sulfhydryls. Inhibition of Ito
      by GSSG was not reversed by washout alone, consistent with the stable nature of
      covalently-modified sulfhydryl groups. However, when myocytes pretreated with
      GSSG were dialyzed with the reducing agent dithiothreitol, Ito amplitude
      increased significantly by 42% (P<0.05). These data suggest that alpha-subunits
      underlying Ito, or associated proteins, have one or more sulfhydryl groups within
      the cytoplasmic domain that directly modulate channel activity in response to
      changes in cell redox state. Redox modulation of Ito channels may be an important
      post-translational mechanism contributing to acute changes in cardiac
      repolarization under conditions of oxidative stress, such as ischemia and
      reperfusion.

PMID- 12505061
TI  - Expression patterns of integrins on quiescent and invasive smooth muscle cells
      and impact on cell locomotion.
AB  - Migration and invasion of human arterial smooth muscle cells (haSMCs) are
      essential steps during the development of atherosclerosis, restenosis, and
      transplant vasculopathy. The molecular mechanisms leading to these processes are
      only incompletely understood. Due to their contact to the surrounding
      extracellular matrix, integrins have been shown to be essentially involved in
      cell locomotion. Therefore, the function of integrins during this process was
      analyzed in an in vitro model which was based on the defined quiescent and
      invasive phenotypes of human haSMCs induced by cell culture conditions. Flow
      cytometric analysis of integrin expression between both phenotypes showed a
      strong upregulation of alpha 5 beta 1 (13.1x) and a modest upregulation of alpha
      vs beta 3 (3.4x) and alpha IIb (3.0x) in invasive haSMCs in comparison to
      quiescent ones. Other integrins analyzed (alpha 2, alpha 3, alpha 4, beta 1) did
      not show differential regulation. Functional inhibition of alpha 5 beta 1 reduced
      cell migration (-29%+/-8), invasion (-49%+/-16), collagen contraction (-125%),
      and attachment to fibronectin. Although, there was a clear discrepancy between
      alpha 5 beta 1 and alpha vs beta 3 expression levels, inhibition of alpha vs beta
      3 (-45%+/-9) reduced haSMC invasion equally. Interestingly, alpha vs beta 3
      unlike alpha 5 beta 1 blockade caused a significant stimulation of collagen
      contraction (+52% vs 154%) with possible implications on vascular remodeling. In
      conclusion, alpha 5 beta 1 blockade or combined alpha 5 beta 1/alpha v beta 3
      blockade by specific antibodies or selective RGD peptides together with local
      drug delivery strategies could be a promising strategy for the therapy of
      restenotic lesions or atheromatous plaques.

PMID- 12505062
TI  - Therapeutic use of muscarinic acetylcholine receptor peptide to prevent mice
      chagasic cardiac dysfunction.
AB  - Therapeutic use of a peptide corresponding to the aminoacid sequence of the
      second extracellular loop of human M2 muscarinic acetylcholine receptor (M2 mAChR
      peptide) was studied. Expression and biological activity of M2 mAChR in
      association with circulating M2 mAChR-related antibodies in cardiac tissue from
      chagasic mice were evaluated. Mice infected or not with trypomastigotes Tulahuen
      strain either treated or not treated with M2 mAChR peptide were sacrificed at 8-9
      weeks post-infection. Morphological, binding and contractility studies were
      performed on all animal groups. Hearts from infected mice showed a mAChR-related
      dysfunction, with a decrease in heart contractility, impaired response to
      exogenous mAChR agonist (carbachol) and a significant reduction of mAChR binding
      sites. Treating infected mice with M2 mAChR peptide reversed those effects.
      Moreover, autoantibodies from infected mice recognized the M2 mAChR peptide. In
      addition, serum from infected mice and the corresponding affinity purified IgG
      was capable of interacting with cardiac mAChR, reducing the number of binding
      sites and inhibiting the contractile response to exogenous agonist. In
      conclusion, (1) the development of alterations in mAChR related to cardiac
      dysfunction, may be associated with the presence of circulating antibodies
      against these receptors and (2) the chronic treatment with M2 mAChR peptide
      prevented infected mice heart dysfunction. The mechanism could be explained by
      the ability of the M2 mAChR peptide to inhibit the chronic interaction of
      autoantibodies specific to mAChR. The implication of M2 mAChR peptide treatment
      in the host's immune response is discussed.

PMID- 12505063
TI  - Appraisal of the role of angiotensin II and aldosterone in ventricular myocyte
      apoptosis in adult normotensive rat.
AB  - Despite previous observations on isolated ventricular myocytes, there are still
      few evidences that angiotensin II induces cardiomyocyte apoptosis in vivo. The
      possibility that aldosterone, the final hormone of the renin-angiotensin
      aldosterone system under Ang II control, can stimulate cardiac apoptosis has not
      yet been explored. Angiotensin II or aldosterone (1mg/kg each) were infused in
      adult normotensive rats for different times, and the number of apoptotic
      ventricular myocyte nuclei was quantified by the TUNEL method, along with caspase
      3 activation. The role of angiotensin II type 1 receptor in vivo was assessed by
      selective blockade with valsartan and ex vivo by binding experiments. In
      addition, myocytes in primary culture were incubated with Ang II or aldosterone
      in presence of spironolactone. Continuous infusion of Ang II induced a rapid,
      AT(1)-mediated increase of apoptotic cardiomyocyte nuclei (from 14+/-9 to 188+/
      35 TdT-labeled nuclei/10(6) after 3h, P<0.005) and of activated caspase-3, that
      normalized after 24h. The normalization was associated with a down-regulation of
      myocardial AT(1) receptors. Aldosterone stimulated cardiomyocyte apoptosis both
      in vivo and in isolated cells, to a similar extent as Ang II. The maximal
      apoptotic rate reported here ( approximately 0.02%) and the transient effect of
      Ang II suggest that myocyte loss by apoptosis is limited in the present model.
      The data on aldosterone-induced ventricular myocyte apoptosis deserve further
      attention to delineate the role of aldosterone in cell death and offer possible
      mechanistic explanations on the benefits afforded by aldosterone receptor
      antagonists in heart failure.

PMID- 12505064
TI  - A novel TCTG(G/C) direct repeat and an A/T-rich HMG2-binding site control the
      expression of the rat cardiac troponin T gene.
AB  - We previously showed that the rat cardiac troponin T proximal promoter (-497bp
      from the transcriptional start site) was sufficient to confer cardiac-specific
      expression of a reporter gene in both cultured cardiomyocytes and transgenic
      mice. This promoter consists of two cis-regulatory modules with high sequence
      similarity. Nucleotides from -319 to -289 (termed D2) and nucleotides from -249
      to -209 (termed F41) contain a TCTG(G/C) direct repeat and an A/T-rich sequence.
      Competition gel mobility shift assays revealed that the same protein factors were
      bound to both D2 and F41. Deletion and religation studies of the promoter
      suggested that D2 acted as an enhancer but could not totally substitute for the
      F41 function. Mutational analyses demonstrated that the direct repeat was
      required for the DNA-binding and promoter activity. Moreover, cardiac-specific
      42kDa proteins and a ubiquitous high mobility group 2 (HMG2) protein were
      identified to be responsible for the binding to the TCTG(G/C) direct repeat and
      the A/T-rich sequence, respectively. Overexpression of HMG2 had differential
      effects on the promoter in cardiomyocytes versus fibroblasts. Our results
      provided the first evidence to support that HMG2 together with tissue-specific
      factors could direct a stimulatory or inhibitory effect on thecardiac troponin T
      gene expression in heart or non-heart tissue, respectively.

PMID- 12505065
TI  - Plasminogen activator inhibitor 1 expression is regulated by the inflammatory
      mediators interleukin-1alpha, tumor necrosis factor-alpha, transforming growth
      factor-beta and oncostatin M in human cardiac myocytes.
AB  - Accumulating evidence points towards a role for proteases and protease inhibitors
      in tissue remodelling and repair in a variety of organs. In particular-besides
      the matrix metalloprotease system-the plasminogen activator (PA)/plasmin system
      has been implicated in these processes in the heart. Urokinase type PA (u-PA) and
      PA inhibitor type 1 (PAI-1) seem to modulate cardiac rupture and infarct healing.
      In this study we aimed to investigate whether inflammatory mediators can regulate
      the expression of components of the PA/plasmin system in human adult cardiac
      myocytes (HACM). We could demonstrate that HACM, isolated from pieces of
      myocardial tissue by mechanical dispersion and characterized by positive
      immunostaining for the cardiac markers troponin I, tropomyosin, cardiotin and
      myocardial muscle-actin, in vitro express PAI-1 and tissue type PA (t-PA) whereas
      u-PA was not detectable in these cells. PAI-1 protein production was increased up
      to twofold by interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF
      alpha) and up to fivefold by transforming growth factor-beta (TGF-beta) and
      oncostatin M (OSM). Similar changes were observed in PAI-1 transcript levels
      after cytokine treatment. t-PA production in HACM was not affected by these
      agonists. No effect of these cytokines on PAI-1 production in fibroblasts
      isolated from human myocardial tissue was seen. In an ex vivo model we could show
      that incubation of pieces of human myocardial tissue with these cytokines also
      resulted in an increase in PAI-1 in cardiac myocytes as evidenced by immuno
      histochemistry. Furthermore we found increased PAI-1 expression in myocardial
      tissue from a patient suffering from acute myocarditis. Thus for the first time
      we provide evidence that inflammatory mediators modulate PAI-1 expression in
      human adult cardiac myocytes in vitro and ex vivo and could demonstrate that PAI
      1 expression is increased in the in vivo setting under inflammatory conditions.
      If the effect on PAI-1 expression brought about by IL-1alpha, TNF-alpha, TGF-beta
      and OSM is not only operative under in vitro and ex vivo conditions but also in
      the in vivo setting one could speculate that these cytokines contribute to
      upregulation of PAI-1 in myocardial tissue and that PAI-1, when upregulated in
      myocardial tissue during inflammatory processes, could serve as a defence
      mechanism against excessive matrix degradation by proteases. Thus we propose a
      role for PAI-1 produced in the heart by cardiac myocytes in cardiac remodelling
      and repair processes.

PMID- 12505066
TI  - The effect of kaolinite intercalation on the structural arrangements of N
      methylformamide and 1-methyl-2-pyrrolidone.
AB  - N-methylformamide (NMF) and 1-methyl-2-pyrrolidone (NMP) were intercalated with
      kaolinite, characterized, and deintercalated for analysis (the NMP was
      intercalated after expansion of the kaolinite layers with NMF). The dynamics of
      guest molecules within the kaolinite lamellae was studied by means of FT-IR and
      liquid state (1)H and (13)C NMR on the NMF and NMP before intercalation and also
      on the deintercalated solutions. Both compounds were deintercalated using water.
      The FT-IR spectra show no significant differences before and after intercalation,
      for either NMF or NMP, indicating that there is no change in molecular
      arrangement as a result of intercalation. (1)H and (13)C NMR investigations
      supported the findings of the FT-IR and indicated that structural arrangement and
      orientation of the guest species remain the same after deintercalation. This work
      provides evidence that intercalation is due to weak physical bonding.

PMID- 12505067
TI  - Measurement of the surface dilational viscoelasticity of adsorbed layers with a
      capillary pressure tensiometer.
AB  - A capillary pressure tensiometer has been set up to measure the dilational
      surface viscoelasticity in liquid-air and liquid-liquid surfactant systems,
      according to the oscillating drop/bubble technique. A specific model which allows
      the dilational surface viscoelasticity to be inferred from the acquired pressure
      data is proposed and the critical points concerning the experimental procedure
      and the data interpretation are discussed. In order to optimize the method, side
      measurements utilizing the same tensiometer to evaluate equilibrium interfacial
      tensions and the system compressibility are coupled to this technique. Some
      nonionic surfactants, polyoxyethylene glycol ethers (C(i)EO(j)) and alkyl
      dimethyl phosphine oxide (C(12)DMPO), at water-air and water-hexane interfaces
      have been investigated by this technique. The measured dynamic dilational
      viscoelasticities are compared with the predictions of theoretical models which
      consider different adsorption mechanisms.

PMID- 12505068
TI  - Nitrogen-doped activated carbon fiber as an applicant for NO adsorbent.
AB  - The effects of nitrogen-doping on adsorption properties of activated carbon
      fibers (ACFs) for NO were investigated. The nitrogen-doped ACFs (N-ACFs) were
      prepared by chemical vapor deposition (CVD) of pyridine at 1023 K for various
      times. The N-ACFs were characterized by N(2) adsorption at 77 K, elemental
      analysis, and X-ray photoelectron spectroscopy (XPS). The nitrogen content
      increases with the pyridine-CVD time. An XPS examination showed that the fraction
      of quaternary nitrogen in the nitrogen structures is almost constant, regardless
      of the CVD times. However, quaternary nitrogen increases remarkably from 54% to
      78% after heat-treatment of N-ACF at 1273 K, although the total nitrogen content
      decreases. The adsorption properties of N-ACFs for NO were examined at 303 K. The
      NO adsorption capacity of N-ACFs increases with the concentration of doped
      nitrogen. The NO adsorptivity of the N-ACF was remarkably enhanced by the heat
      treatment at 1273 K.

PMID- 12505069
TI  - Influence of demulsifiers of different structures on interfacial dilational
      properties of an oil-water interface containing surface-active fractions from
      crude oil.
AB  - The influences of two commercial demulsifiers that have a straight chain and
      branch chain, respectively, on the dilational viscoelasticity of an oil-water
      interfacial film containing surface-active fractions from crude oil were
      investigated. The branch-chain demulsifier AE-121 could efficiently substitute
      surface-active fractions of different average molecular weights from the oil
      water interface, while straight-chain SP-169 could only efficiently substitute
      those of large average molecular weight. It was apt to form a mix-adsorption
      layer with surface-active fractions of small average molecular weight. The
      results showed that the molecular size (or represented by average molecular
      weights) of the surface-active fractions was an important factor influencing the
      reciprocity of demulsifiers and surface-active fractions at the oil-water
      interface. This effect could be well explained by the difference between sizes of
      surface-active fraction molecules and vacancies between demulsifier molecules at
      the interface. The results of SDBS also proved this explanation.

PMID- 12505070
TI  - Adsorption energy distribution model for VOCs onto activated carbons.
AB  - An adsorption isotherm model was proposed for two types of volatile organic
      compounds (VOCs) on a heterogeneous carbon surface. The Langmuir isotherm was
      used as a local isotherm for describing heterogeneous surfaces to obtain the
      adsorption energy distribution. The adsorption temperature studied ranged from 30
      to 50 degrees C, and the pressure of VOCs varied from 0 to 0.35 atm. The present
      model differed from previous studies in assuming that the pre-exponential factor
      was not to be a constant. The pre-exponential factors were determined directly
      from the experimental data, and the result empirically showed that the pre
      exponential factor was correlated with the adsorption energy by a simple
      exponential function. We found that both adsorption energy distributions of two
      VOCs were essentially step functions over the restricted pressure range,
      indicating adsorbates on the carbon surface with its own uniform distribution. By
      incorporation of the energy distribution and the relationship between the pre
      exponential factor and the adsorption energy, the adsorption isotherms for the
      two VOCs on the carbons can be well predicted.

PMID- 12505071
TI  - Influence of the layer charge and clay particle size on the interactions between
      the cationic dye methylene blue and clays in an aqueous suspension.
AB  - The spectroscopic behavior of the dye MB in suspensions of different clays have
      been used for evaluating layer charge density influence on the adsorption
      properties of the particles. The clays with higher charge density, like SAz-1 and
      SCa-3, promote a higher aggregation and do not show deaggregation at longer
      times, so that practically only the aggregate peak at approximately 570 nm is
      observed, without any change with time. This is due to, on one side, the larger
      particle size that decreases the surface area available for adsorption.
      Additionally, the clay layers will be held together more tightly, avoiding the
      migration of the dye to the interlamellar region. On the other hand, SWy-1,
      having a lower charge density, shows a completely different behavior. The dye
      molecules, initially adsorbed as aggregates on the outer surface of the clay,
      deaggregate to form monomers that migrate to the interlamellar spaces, giving
      rise to absorption bands at 670 and 760 nm. Experiments using Ca-exchanged SWy-1,
      variation of the ionic strength by addition of salt, and the use of different
      size fractions of the clays confirm the finding that the main factor ruling the
      adsorption behavior of the probe is the size of the clay particles.

PMID- 12505072
TI  - Catalytic effects of galactose oxidase on micelle-forming galactolipids.
AB  - Catalytic effects of galactose oxidase on the oxidation of beta-D-galactose
      carrying lipids with an oligo-ethylene glycol spacer (number of ethylene glycol
      units (n)=1, 2, 3, 6, 9, 13, and 20) were examined. The affinity of galactose
      oxidase for the galactose residue in the amphiphile (estimated by the inverse of
      the Michaelis constant, K(m)) was much higher than those for free D-galactose and
      small beta-D-galactopyranosides, and dependent on the length of the ethylene
      glycol spacer. That is, both below and above the critical micellar concentration,
      the 1/K(m) values decreased with an increase in the n value. The effectiveness of
      the enzyme, which can be estimated by the k(cat)/K(m) value, showed the same
      tendency as the 1/K(m) value. These results could be attributed to the role of
      the nonpolar environment around the galactose residue in the binding by the
      enzyme. A significant enhancement of the enzymatic oxidation of galactose residue
      on the liposome surface was also observed.

PMID- 12505073
TI  - Monitoring surfactant-induced hemolysis by surface tension measurement.
AB  - Surface tension measurements were employed to monitor the erythrocyte hemolysis
      process induced by surfactants. Two types of surfactants were used: the cationic
      surfactant DTAB and the anionic surfactant SDS. During DTAB-induced hemolysis,
      the changes in surface tension clearly demonstrate three stages. The first stage
      is characterized by surface tension increase, which is explained by surfactant
      removal from the suspending solution, due to adsorption onto cell membranes. In
      the second stage, surface tension remains constant, implying that equilibrium is
      attained between the membrane-bound surfactant and the surfactant in solution.
      The third stage is characterized by surface tension decrease that begins
      simultaneously with measurable cell-interior release, and lasts until hemolysis
      is completed. With SDS-induced hemolysis, the same three stages are observed at a
      low concentration; however, fluctuational increase in surface tension is obtained
      for higher concentrations. The latter is explained by additional adsorption of
      surfactant to solubilized membrane fragments.

PMID- 12505074
TI  - Wetting of liquid droplets on living cells.
AB  - We report here the formation of adhesive conjugates between living cells and
      properly tailored colloidal liquid droplets bearing a cationic surfactant. We
      show that the droplets could wet cell surface with a well-defined contact angle,
      allowing direct determination of the energy of adhesion. We also describe the
      effect of cationic surfactant concentration on adhesion efficiency. This provides
      new tools to probe living cell surface properties and find practical laws for
      cell adhesion on well-defined surfaces.

PMID- 12505075
TI  - Gas bubbles in viscous liquids and melts.
AB  - The basic set of equations and boundary conditions for viscous liquids and melts
      with gas has been derived. The flux of bubbles in the space of sizes,
      distribution of bubbles with respect to size, number of bubbles in the unit
      volume, and swelling of the system of viscous gas with liquid have been found.
      The initial and intermediate stages of the diffusion decomposition of the
      metastable system of viscous liquid with gas are considered.

PMID- 12505076
TI  - Size-selective chemical synthesis of tartrate stabilized cobalt ferrite ionic
      magnetic fluid.
AB  - Ionic magnetic fluid (ferrofluid) is a stable suspension of magnetic
      nanoparticles in water. Cobalt ferrite nanoparticles are interesting in view of
      high-density recording storage. The size of the magnetic particles strongly
      influences the physical properties of the ferrofluids. In this study, we describe
      the synthesis of ionic magnetic fluid in the presence of tartrate ions. By
      varying the amount of organic ligands, nanoparticles in a large range of size are
      obtained: the mean diameter varies from 3 to 10 nm. The effect of tartrate ions
      on the stability of the ionic magnetic fluid is also studied in relation with the
      size of the magnetic particles and the amount of adsorbed ligand.

PMID- 12505077
TI  - Spontaneous formation of Ag nanoparticles in dimethylacetamide solution of
      poly(ethylene glycol).
AB  - The spontaneous formation of Ag nanoparticles in a dimethylacetamide (DMAC)
      solution of poly(ethylene glycol) (PEG) was studied. FTIR analysis showed the
      formation of carbonyl groups, revealing that PEG acted as not only a protective
      agent but also a reducing agent in the formation of Ag nanoparticles. Since no
      significant reactions were observed when poly(tetramethylene glycol) (PTMG) was
      used to replace PEG or acetonitrile was used to replace DMAC, it was suggested
      that PEG molecules might be coiled to form pseudo-crown ether cavities, in which
      Ag complexes were bound to the oxyethylene groups and reduced, and that the use
      of a solvent which might appropriately solvate the Ag salt was important for the
      formation of Ag nanoparticles. In addition, the mean diameters of the resultant
      Ag nanoparticles were 3.8-9.0 nm, increasing with increasing AgNO(3)
      concentration. A sufficiently high PEG concentration relative to AgNO(3) was
      necessary for the formation of smaller Ag nanoparticles. This work provided a
      simple route for the in situ synthesis of Ag nanoparticles.

PMID- 12505078
TI  - The intercalation of a vermiculite by cationic surfactants and its subsequent
      swelling with organic solvents.
AB  - We have measured the dimensions of the interlamellar space following
      intercalation of a vermiculite by a range of cationic surfactants and followed
      the subsequent swelling of the organoclay compounds with several organic
      solvents. A single vermiculite (Eucatex) was used with three series of
      surfactants, N-alkyltrimethylammonium bromides, N,N'-dialkyldimethylammonium
      bromides, and the gemini cationic surfactants, alpha,omega-bis (N
      alkyldimethylammonium) alkanes. In all cases well-defined stoichiometric
      compounds are obtained and the amount of surfactant intercalating the layer
      indicates that there are two factors controlling this amount, charge
      neutralization of the clay and hydrophobic packing. Packing arguments are used to
      deduce the fraction of non-charge-neutralizing material in the interlamellar
      space. It is clear that by altering the surfactant charge and structure it is
      possible to control the degree to which adsorption beyond charge neutralization
      occurs in these complexes, which is important when the capacity of such complexes
      to sorb other materials is considered. The general pattern of swelling of the
      surfactant/vermiculite complex by toluene suggests that the maximum expansion of
      the intralamellar space is limited by the longest chain in the surfactant. In
      contrast to earlier results we found that these vermiculites could be swollen by
      alkanes as well as aromatic solvents. This is attributed to the greater
      hydrophobicity of the interior of an organoclay formed from a clay of higher
      charge density.

PMID- 12505079
TI  - Effects of various thiol molecules added on morphology of dendrimer-gold
      nanocomposites.
AB  - Interactions between poly(amidoamine) dendrimer (PAMAM)-gold nanocomposites and
      alkanethiols and between the former nanocomposites and thiol-modified
      poly(amidoamine) dendrons in ethyl acetate were investigated by adding
      alkanethiols, such as 1-propanethiol and 1,3-propanedithiol, and thiol-modified
      poly(amidoamine) dendrons, generations 0.5 and 2.5 (G0.5-SH and G2.5-SH). The
      PAMAM dendrimers with surface methyl ester groups used were generations 1.5 and
      5.5 (G1.5 and G5.5). The mean particle sizes of PAMAM-gold nanocomposites were
      about 2.1 for G1.5 and 2.4 nm for G5.5. In both nanocomposite systems where 1
      propanethiol and 1,3-propanedithiol were added, the mean particle size was about
      4 nm, twice that of the systems where these thiols were not added. Increasing the
      addition of 1,3-propanedithiol made the average particle size smaller for both
      nanocomposites systems. To compare with alkanethiol, thiol-modified
      poly(amidoamine) dendron with a highly branched structure on one side was
      synthesized. Using G2.5-SH as a protective agent, dendron-gold nanocomposites
      with mean diameters of 3 to 4 nm were obtained. The difference in particle size
      was seen only when the combination of PAMAM-gold nanocomposites and thiol
      modified dendron was less sterically dense, modified dendron (G0.5-SH). The
      mechanisms for morphology changes in the dendrimer-gold nanocomposites by the
      addition of these thiols are discussed.

PMID- 12505080
TI  - Electrokinetic characterization of porous plugs from streaming potential coupled
      with electrical resistance measurements.
AB  - The zeta potential of mixed nickel-iron oxide particles is evaluated by a new
      laboratory instrument. This latter allows the measurement of streaming potential
      together with the electrical resistance of porous plugs. The conductivity of
      electrolyte inside plug (pore conductivity) is deduced from electrical resistance
      measurements and is used together with streaming potential to evaluate the zeta
      potential by accounting for the surface conduction phenomenon. It is shown that
      neglecting the surface conduction phenomenon leads to a substantial
      underestimation of the zeta potential. The coupled measurements of streaming
      potential and plug electrical resistance yield zeta potential values that are in
      very good agreement with those obtained by electrophoresis. The densification of
      the porous plug with increasing pressure increments is put in evidence by the
      decrease in measured streaming potentials. Electrical resistance measurements
      make it possible to account for the increase in surface conductivity resulting
      from the more compacted structure of the plug. By doing so, the calculated zeta
      potential is found to be virtually independent of the pressure difference
      involved in streaming potential experiments, whereas the negligence of surface
      conduction phenomenon leads to a decrease in the apparent zeta potential with
      increasing pressure level.

PMID- 12505081
TI  - Determination of coagulation coefficients and aggregation kinetics for charged
      aerosols.
AB  - A new method has been developed which allows determination of the coagulation
      coefficient of two oppositely charged particles experimentally. For this purpose,
      quasi-monodisperse particles of different sizes and morphology were used to study
      the influence of different parameters on the coagulation coefficient. A good
      agreement between experimental results and the classic Fuchs' theory was obtained
      when including a method accounting for particle nonsphericity. In experiments
      with polydisperse bipolarly charged aerosols, no principal differences to
      uncharged aerosols were found when a dimensionless representation was used.
      Changes in particle number concentration and geometric mean diameter can be
      described by simple empirical expressions.

PMID- 12505082
TI  - Contact angle and film pressure: study of a talc surface.
AB  - Talc samples in both sheet and powder form are studied by adsorption calorimetry
      and adsorption isotherm techniques. A model is used to determine the solid
      surface energy, the solid surface tension and the dispersive, acidic, and basic
      components of these terms. These results are introduced in an approximate
      equation relating adsorption to contact angle data. Experimental contact angles
      are in correct agreement with this approach. The Neumann equation of state is
      used to fit the data and discussed. It appears as a numerical form of the general
      equation taking into account gas adsorption and film pressure. Behaviors of talc
      in contact with liquids do not appear very different whether the solid is in
      sheet or powder form.

PMID- 12505083
TI  - Determination of zeta potentials of polymeric nanoparticles by the conductivity
      variation method.
AB  - An easy method of measurement of the zeta potentials of sub-50-nm polymeric
      nanoparticles is suggested. Although zeta potential measurements of nanoparticles
      or emulsions above 50 nm have been successfully carried out, zeta potentials of
      emulsions or nanoparticles below 50 nm could not be precisely measured in the
      region of extremely low conductivity by conventional electrophoresis with a He-Ne
      laser. However, zeta potentials of sub-50-nm nanoparticles were measured in the
      region of thin electrical double layers by addition of sodium chloride and zeta
      potentials in the condition without sodium chloride could be predicted by
      extrapolation of the measured potentials. The electrophoretic mobility of 150-nm
      nanoparticles stabilized with sodium dodecylsulfate was the same as that
      calculated from extrapolation of the measured ones. The zeta potentials of sub-50
      nm nanoparticles stabilized with sodium dodecylsulfate could be calculated by the
      same procedure.

PMID- 12505084
TI  - Attachment of alkyltrichlorosilanes to the terminal 3,5-dihydroxyphenyl moiety of
      a self-assembled thiol monolayer on gold.
AB  - The synthesis of 5-(6-mercaptohexyloxy)-1,3-dihydroxybenzene and the formation of
      a self-assembled monolayer on polycrystalline gold using this compound are
      described. Methyltrichlorosilane and (tridecafluoro-1,1,2,2
      tetrahydrooctyl)trichlorosilane were attached to the 3,5-dihydroxyphenyl terminus
      of the monolayer. The modified surfaces were studied by contact angle
      measurement, XPS, and cyclic voltammetry. High contact angles of 119 degrees -128
      degrees were observed for the semifluoroalkylsilyl-functionalized monolayer.
      These high contact angles were maintained after subjecting the surface to, e.g.,
      boiling in water or heating in air to 300 degrees C. Characterization of the
      silane-modified monolayers by XPS indicated more than one layer of silane present
      at the top of the monolayer. The thickness was reduced after boiling the cross
      linked monolayers in H(2)O, however, maintaining high contact angles. Cyclic
      voltammetry studies revealed that the semifluoroalkylsilyl-functionalized surface
      showed a higher blocking capability and a higher electrochemical stability than
      the parent monolayer.

PMID- 12505085
TI  - Correlations between surface and interface energies with respect to crystal
      nucleation.
AB  - The energetic chemical and structural properties of interfaces between solid and
      liquid metals are of great interest in numerous applications. However, solid
      liquid interfacial energies of metals are often determined by nucleation
      experiments, requiring particular attention to the measurements so obtained. The
      purpose of this paper is to conduct an analysis of the level of liquid
      undercooling of 3d-, 4d-, and 5d-transition metals, as well as of other common
      undercooled elements, through a critical survey of thermophysical data and
      experimental results. As already pointed out for the liquid-vapor surface energy
      sigma(LV), the solid-liquid interface energy sigma(LS) determined from the
      maximum amount of liquid undercooling is well connected to the position of the
      element in the periodic table, leading to the individualization of each behavior,
      including the size of the critical nucleus. The beta ratio of sigma(LS)/sigma(LV)
      is demonstrated to be an interesting dimensionless number by which to classify
      the elements into distinctive groups. No significant unexplained anomaly is
      identified, except for Co, supporting the belief that Turnbull's classical theory
      furnishes a robust support to describe the crystal nucleation in pure elements.

PMID- 12505086
TI  - The thermocapillary migrations of two bubbles in microgravity environment.
AB  - The thermocapillary motion of two bubbles along their line of centers in a
      uniform temperature gradient is investigated theoretically. The bubbles are
      moving in the direction of the temperature gradient. And the interaction between
      the leading bubble and the trailing one becomes significant as the separation
      distance between them is decreased greatly so that the bubble interaction is
      considered in this case. The appropriate equations of momentum and energy are
      solved using the method of reflections. In order to proceed analytically, sets of
      transformations between two coordinates are obtained. By using these
      transformations and the reflection process, accurate migration velocities of
      these two bubbles in the microgravity environment are derived for the limit of
      small Marangoni and Reynolds numbers. These results are employed to describe the
      thermocapillary motion of two bubbles and to estimate the effects of bubble size
      and the thermal gradient on the interaction between two bubbles. All of our
      results for the migration of the two bubbles demonstrate that the approach of the
      second bubble to the first one intensifies the mutual interaction between these
      two bubbles and yields some interesting thermocapillary motions.

PMID- 12505087
TI  - Thermodynamics and micellar properties of tetradecyltrimethylammonium bromide in
      formamide-water mixtures.
AB  - The effect of formamide on the micellization of tetradecyltrimethylammonium
      bromide has been investigated by conductance and fluorescence probe experiments.
      The critical micelle concentration and the degree of counterion dissociation of
      micelles were obtained from conductance measurements in the temperature range of
      20 to 40 degrees C. It was found that these two parameters increase with both
      temperature and formamide content in the solvent system. The thermodynamic
      parameters of micellization were estimated using the equilibrium model of micelle
      formation. The standard free energy of micellization was found to be negative in
      all cases and becomes less negative as the formamide content in the mixed solvent
      increases, but it is roughly independent of temperature. Although the entropic
      contribution was found to be larger than the enthalpy one, in particular at lower
      temperatures, an enthalpy-entropy compensation effect was observed for all
      systems. Micellar aggregation numbers were determined by the static quenching
      method, using pyrene as a probe and cetylpyridinium chloride as a quencher. The
      observed decrease in the micelle aggregation number, which is controlled by the
      increase in the surface area per headgroup, was attributed to an enhanced
      solvation in formamide rich solvent mixtures. Changes in the pyrene 1:3 ratio
      index, indicating a more polar environment, are consistent with an increased
      micellar solvation. Fluorescence polarization of both coumarin 6 and fluorescein
      are indicative of a decrease in microviscosity with cosolvent addition. The data
      on fluorescence anisotropy of coumarin 6 were analyzed using the wobbling in cone
      model. Data indicated the formation of micelles with a less ordered structure as
      the formamide increases in the solvent system.

PMID- 12505088
TI  - Layered droplet microstructures in sheared emulsions: finite-size effects.
AB  - We investigate the influence of confinement on the steady state microstructure of
      emulsions sheared between parallel plates, in a regime where the average droplet
      dimension is comparable to the gap width between the confining walls. Utilizing
      droplet velocimetry, we find that the droplets can organize into discrete layers
      under the influence of shear. The number of layers decreases from two (at
      relatively higher shear rates) to one (at lower shear rates), as the drops grow
      slightly larger due to coalescence. We argue that the layering and overall
      composition profile may be controlled by the interplay of droplet collisions
      (which can cause separation of droplet centers in the velocity gradient
      direction), droplet migration toward the centerline (due to wall effects), and
      droplet packing constraints. We also study the effects of mixture composition on
      droplet microstructure, and summarize these results in the form of a morphology
      diagram in the parameter space of mass fraction and shear rate. We find that
      formation of strings of the suspended phase (reported earlier by our group in
      flow-visualization studies on confined emulsions) is observed over a broad
      composition window. We also find a stable (nontransient) morphology wherein the
      droplets are arranged in highly ordered pearl-necklace chain structures.

PMID- 12505089
TI  - Interactions between a nonionic gemini surfactant and cyclodextrins investigated
      by small-angle neutron scattering.
AB  - The microstructure of complexes between hydroxypropyl-cyclodextrins (HPCDs)
      (alpha, beta, and gamma) and a novel gemini surfactant has been investigated by
      small-angle neutron scattering (SANS). This nonionic hetero-gemini surfactant
      (denoted NIHG750) contains two hydrophobic groups and two hydrophilic groups. One
      is a methyl-capped polyoxyethylene chain with 16 oxyethylene units and the other
      is a secondary hydroxyl group. Various form factor models have been considered
      for fitting the SANS data. Spherical aggregates (25 to 40 A) with a size slightly
      larger than that of NIHG750 micelles (about 23 A) appear in mixed systems. These
      could be micellar aggregates partly covered with a few cyclodextrin molecules. In
      addition, the results indicate rod formation (r approximately 8 A, L
      approximately 70 A) for the NIHG-HPCD complexes. This result is consistent with
      the threading of HPCDs onto NIHG750 to such an extent that the surfactant
      molecule takes an extended conformation at high levels of HPCD. Also, the results
      indicate that HPCDs may interact with the oxyethylene groups of the spherical
      micellar aggregates leading to an increase in micelle size and a gradual
      transformation to rod-shaped aggregates. The tendency to form rods increases in
      the order gamma-CD<alpha-CD<beta-CD. An increase in HPCD concentration results in
      an increased amount of rods in the system. All spherical aggregates disappear at
      relative amounts of HPbetaCD above 4 to 5 (molar ratio). However, for HPalphaCD
      and HPgammaCD spherical aggregates coexist with rod shaped aggregates in the
      whole range of concentrations investigated here.

PMID- 12505090
TI  - Thermodynamic properties of the aqueous solution of potassium salts of some 4
      ((alkylcarbonyl)amino)-2-hydroxybenzoic acids at 298 and 313 K.
AB  - To understand the aggregation behavior of surface-active ligands with a salycilic
      polar head, we undertook a systematic study of some classes of anionic
      surfactants where the presence and the position of the -OH and the carboxylic
      group differ. This paper reports the dilution heats at 298 and 313 K of aqueous
      solutions of potassium 4-((alkylcarbonyl)amino)-2-hydroxybenzoate (KPAS-C(n)
      where n stands for the number of carbon atoms in the chain) in KOH at 0.1 m,
      measured as a function of concentration. From the experimental data, apparent and
      partial molar enthalpies vs concentration were obtained. By using a pseudo-phase
      transition approach, the enthalpy changes upon micelle formation (DeltaH(m)) and
      assuming that in the restricted range of temperature examined heat capacities are
      constant, the heat capacity changes have been obtained. Micelle formation
      enthalpies are seen to be additive with a group contribution for the methylene
      group of -1.5+/-0.1 kJ mol(-1) per group at 298 K and -2.3+/-0.1 kJ mol(-1) per
      group at 313 K, comparable with that obtained for similar anionic compounds in
      the same experimental conditions and for N-alkylnicotinamide chlorides (cationic
      surfactants). The -CH(2)- group contribution to the micelle formation heat
      capacities is -53+/-1 J K(-1) mol(-1).

PMID- 12505091
TI  - Dynamic Surface Properties of Poly(vinylpyrrolidone) Solutions.
AB  - The dynamic surface tension and the complex dynamic surface elasticity of
      poly(vinylpyrrolidone) (PVP) solutions were measured in the concentration range
      10(-5) wt% up to about 1 wt%. The surface tension changed slowly with time at low
      (<10(-4) wt%) and high concentrations (>0.1 wt%). At low concentrations this is a
      consequence of the slow transport by diffusion of PVP molecules from the depth of
      the bulk phase to the surface. At high concentrations the time effect is
      unexpected and probably the result of PVP contamination of high surface activity.
      The dynamic surface elasticity of PVP solutions gradually decreases with
      increasing concentration up to the range of high concentrations (>0.1 wt%) where
      an abrupt increase in the elasticity caused by the adsorbed impurity is observed.
      At low and medium concentrations the viscoelastic behavior of PVP adsorbed films
      is similar to that of the previously investigated poly(ethylene oxide) and
      poly(ethylene glycol) films and is determined by the number of loops and tails
      protruding into the bulk phase.

PMID- 12505092
TI  - Effects of aminoacids on the autooxidation of 3,5-di-tert-butylcatechol in the
      presence of surface-active copper(II) complexes.
AB  - The rate of autooxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) in the presence
      of micelles formed from mixing equal concentrations of [Cu(C(12)-tmed)Br(2)]
      (where C(12)-tmed is N,N,N'-trimethyl-N'-dodecylethylenediamine) and several
      amino acids has been investigated. It was found that the rate in air-saturated
      solution is very much dependent on pH, which affects the availability of
      copper(II) coordination site for the catechol and the degree of micellization. At
      a given pH, the rates in [Cu(C(12)-tmed)Br(2)] micellar media are greatly
      enhanced in the presence sodium halide.

PMID- 12505093
TI  - Physicochemical properties of quaternized poly(amidoamine) dendrimers with four
      octyl chains.
AB  - A cationic dendrimer-type tetrameric surfactant (C(8)qbG0) with four octyl chains
      and four ammonium groups was synthesized by the reaction of poly(amidoamine)
      dendrimers with generation of zero and glycidyldimethyloctylammonium bromide. The
      physicochemical properties of C(8)qbG0 and of their mixtures with sodium dodecyl
      sulfate (SDS) were characterized by investigating surface tension, electrical
      conductivity, fluorescence of pyrene, and dynamic light-scattering. The critical
      micelle concentration (cmc) of C(8)qbG0 was 13 mmol dm(-3) at the concentration
      of one terminal group and the surface tension at the cmc attained 34 mN m(-1).
      The occupied area of C(8)qbG0 was 1.94 nm(2) molecule(-1), indicating that the
      tetrameric dendrimers adsorb widely at the air/water interface. The fluorescence
      intensity ratio of the first-to-third band in the emission spectra of pyrene for
      C(8)qbG0 decreased from around the cmc obtained by the surface tension
      measurement. The hydrodynamic radius of C(8)qbG0 determined by dynamic light
      scattering was about 1.3 nm. The addition of SDS to the aqueous solutions of
      C(8)qbG0 enhanced the surface activities; the mixtures exhibited lower cmc, lower
      surface tension, and higher solubilization of pyrene than SDS alone. It was found
      that the mixtures of C(8)qbG0 and SDS form large aggregates due to the
      interactions between their alkyl chains as well as hydrophilic groups.

PMID- 12505094
TI  - Effects of certain micronutrients and melatonin on plasma lipid, lipid
      peroxidation, and homocysteine levels in rats.
AB  - BACKGROUND: Numerous studies suggest an association between high intake of
      antioxidant vitamins and fish oil and reduced risk of coronary heart disease.
      Hyperhomocysteinemia has also been identified as an independent risk factor for
      arteriosclerosis. In this paper, we aimed to evaluate the effects of vitamin E,
      vitamin C, vitamin C 6 palmitate (VC6P), lipoic acid, fish oil, and melatonin
      supplementation on lipid peroxidation, plasma lipid, and homocysteine (Hcy)
      levels in rats. METHODS: Animals were divided into seven groups: one was used as
      control and each remaining group was supplemented with one substance for 6 weeks.
      All substances were dissolved in olive oil and injected intraperitoneally (i.p.)
      with the exception of vitamin C, which was dissolved in drinking water. Plasma
      Hcy, lipid peroxidation, and lipids were determined. RESULTS: Plasma
      malondialdehyde (MDA) levels decreased significantly in melatonin (p <0.01),
      lipoic acid (p <0.01), and vitamin E (p <0.05) groups. On the other hand,
      supplementation with vitamin C and VC6OP lowered MDA levels moderately but not
      significantly (p >0.05). Fish oil supplementation caused a slight but
      insignificant increase in plasma MDA levels (p >0.05). Plasma lipid levels in
      animals treated with melatonin, vitamin E, vitamin C, lipoic acid, and fish oil
      were significantly lower than those of controls; however, treatment of rats with
      VC6P has no significant effect on plasma lipid level. Melatonin and fish oil
      administration significantly lowered plasma Hcy levels, whereas VC6P elevated its
      level. There was no significant effect of vitamin E, vitamin C, and lipoic acid
      on levels of plasma Hcy. CONCLUSIONS: Our data suggest that supplementation with
      antioxidants appears to be hypolipidemic. In addition to these beneficial
      effects, administration of melatonin and fish oil deserves careful consideration
      as a measure to lower plasma Hcy levels and reduce risk of cardiovascular
      diseases.

PMID- 12505095
TI  - Comparison of two commercially available avidity tests for toxoplasma-specific
      IgG antibodies.
AB  - BACKGROUND: IgG anti-Toxoplasma avidity tests have proven useful to discriminate
      between recent and distant infection in management of pregnant women with anti
      Toxoplasma-IgM antibodies. This study was performed to compare two commercially
      available IgG anti-Toxoplasma avidity test kits. METHODS: Sixty-four samples
      positive for IgM and IgG anti-Toxoplasma antibodies were analyzed with two IgG
      anti-Toxoplasma avidity tests: VIDAS Toxo IgG avidity kit (BioMerieux, Marcy
      l'Etoile, France) and Toxoplasma gondii IgG avidity EIA kit (Labsystems,
      Helsinki, Finland). Samples were obtained from both pregnant women and subjects
      in different clinical settings. RESULTS: Of 64 sera positive in both VIDAS Toxo
      IgG and VIDAS Toxo IgM tests, 19 (29.7%) had high avidity antibodies in VIDAS and
      17 (26.6%), high avidity antibodies in Labsystems kit. A total of 48 (75.0%) of
      64 sera showed concordant results between VIDAS and Labsystems Toxo IgG avidity
      tests; one (1.2%) serum sample showed discordant results and in 15 (23.4%) sera,
      results were high or low in one test and borderline in the other. Overall
      correlation coefficient for results obtained in both tests was 0.80 (0.60 in sera
      of pregnant women and 0.88 in sera of other patients, respectively). CONCLUSIONS:
      Correlation between results obtained in BioMerieux and Labsystems Toxo IgG
      avidity kits in sera from pregnant women as well other individuals was high.
      BioMerieux assay possesses the advantage of automatization but requires the VIDAS
      machine; in contrast, Labsystems assay is less costly but requires time-intensive
      manual performance and calculation of test results.

PMID- 12505096
TI  - Relationship of insulin resistance and overweight with cortisol and
      dehydroepiandrosterone-sulfate levels.
AB  - BACKGROUND: Our objective was to assess the relationship of hormones such as
      cortisol and dehydroepiandrosterone-sulfate (DHEA-S) with insulin resistance and
      overweight. METHODS: We designed and conducted a cross-sectional, observational
      survey consisting of home visits within a previously defined area of Mexico City.
      The study included 303 apparently healthy volunteers from a middle-class
      socioeconomic urban community. We measured glucose, cholesterol, triglycerides,
      insulin, cortisol, and DHEA-S. Insulin resistance (IR) was defined as belonging
      to the first quartile of fasting glucose/insulin ratio (G/IR) distribution or
      fourth quartile of IR (HOMA). Overweight was defined as body mass index (BMI) >
      or =25 kg/m(2). RESULTS: To predict IR in women < or =35 years of age, principal
      component analysis (PCA) disclosed three components: 1) cholesterol, BMI, and
      diastolic blood pressure (DBP); 2) cholesterol, triglycerides, and cortisol, and
      3) dehydroepiandrosterone-sulfate [DHEA-S]. Solely the latter (DHEA-S) was
      significantly associated with IR (odds ratio [OR] = 1.80, confidence interval 95%
      [CI 95%] 1.11-2.91, p = 0.015). For men < or =35 years of age, there were two
      components: 1) cholesterol, triglycerides, BMI, and DBP, and 2) DHEA-S,
      cholesterol, and cortisol. Component 1 was significantly associated with IR (OR =
      5.65; CI 95% 1.62-19.65, p = 0.006). To predict overweight in women >35 years of
      age, there were three components, including 1) cholesterol and triglycerides, 2)
      cortisol, and 3) DHEA-S and G/IR. Component 2 was significantly associated with
      overweight (OR = 0.38, CI 95% 0.23-0.64, p = 0.000). CONCLUSIONS: In women < or
      =35 years of age, high DHEA-S levels were associated with insulin resistance,
      which suggests that in young women DHEA-S exerts anti-estrogenic action, perhaps
      caused by its competitive binding with the estrogen receptor. Additionally, in
      women >35 years of age, low cortisol levels were associated with overweight.
      These associations were not identified for the male subgroup.

PMID- 12505097
TI  - Diabetes mellitus vs. Raynaud disease: different lung vascular bed disorders.
AB  - BACKGROUND: In type II diabetes mellitus there are few data concerning pulmonary
      function abnormalities. In normal subjects and in patients with primary Raynaud
      phenomenon, cold pressor test induces a decrease in carbon monoxide single-breath
      diffusing capacity (DL,co) but not in secondary Raynaud phenomenon. Our objective
      was to assess evaluation of lung diffusion capacity postural changes in diabetes
      mellitus and in secondary Raynaud phenomenon, two diseases with different
      pulmonary capillaries functional disorders. METHODS: Twenty-five patients with
      type II diabetes mellitus (mean age 52.24 years), 17 patients with secondary
      Raynaud phenomenon (mean age 47.06 years), non-smokers without pulmonary or heart
      disease, and 26 healthy matched subjects (mean age 47.50 years) underwent lung
      diffusion capacity measurements by single-breath method also corrected by
      alveolar volume (DL,co) in sitting and supine positions. RESULTS: Patients with
      diabetes mellitus exhibited lower values of DL,co and DL,co/VA measurements in
      comparison with subjects with Raynaud phenomenon and control group (p <0.01).
      Additionally, they had a significant decrease in DL,co in supine compared to
      sitting position (83.88 +/- 16.53 vs. 89.68 +/- 18.03, p = 0.023). To the
      contrary, supine position in secondary Raynaud phenomenon and in control group
      after cold pressor test showed a significant increase in DL,co/VA (120.93 vs.
      109.78 in Raynaud and 114.36 vs. 99.47 in control group, p <0.001). CONCLUSIONS:
      Postural changes of lung diffusion capacity could be used as a simple, non
      invasive method to detect vascular disease resulting from different
      pathophysiologic mechanisms such as diabetes mellitus and Raynaud phenomenon.

PMID- 12505098
TI  - Fc receptor blockade in patients with refractory chronic immune thrombocytopenic
      purpura with anti-D IgG.
AB  - BACKGROUND: This is an evaluation of the treatment of 63 patients with chronic
      immune thrombocytopenic purpura (54 splenectomized and nine nonsplenectomized)
      with weekly doses of anti-D (IgG)-coated red blood cells (RBCs). METHODS: All
      patients were given one 5-15 microg/kg/dose of intravenous (i.v.) anti-D (IgG)
      coated RBCs per week (average of 300 microg/dose/week) for a median 3-month
      period (3-6 months). Treatment modality was evaluated on a weekly basis by
      platelet counts, measuring of hemoglobin levels, and performance of Coombs tests.
      RESULTS: All patients presented a clinical response. Fifty-two patients (82.5%)
      increased their platelet count (PC) and 45 (69.8%) increased their PC >50 x
      10(9)/L. In 34 cases, response was sustained. Six of nine nonsplenectomized
      patients (67%) increased PC, thus avoiding splenectomy; four patients attained a
      stable complete response (CR). Similar platelet responses were observed in
      homozygous and heterozygous Rh (D)-positive patients (Rh/Hr phenotypes).
      Currently, after >10 years, 43 patients present a now permanent complete response
      with platelet count >50 x 10(9)/L. Ten patients subsequently decreased their
      platelet count, although they were able to attain CR after receiving six doses of
      anti-D (IgG)-coated RBCs. CONCLUSIONS: Based on our study of Fc receptor blockade
      treatment with anti-D (IgG)-coated RBCs with the most difficult cases of ITP,
      which resulted in a 69.8% successful response rate, we concluded that weekly
      prescription of anti-D (IgG)-coated RBCs is an effective approach to treating
      chronic refractory ITP.

PMID- 12505099
TI  - Binding of rheumatoid and lupus synovial fluids and sera-derived human IgG
      rheumatoid factor to degalactosylated IgG.
AB  - BACKGROUND: Altered glycosylation of immunoglobulin G (IgG) has been demonstrated
      in patients with rheumatoid arthritis (RA). Specificity of IgG rheumatoid factor
      (RF) in recognizing degalactosylated IgG (Fab)(2) and Fc was analyzed in the
      present study. METHODS: (Fab)(2) and Fc fragments were prepared from IgG of
      normal healthy subjects. Enzymes, including peptide-N-glycosidase (PNGase),
      neuraminidase, and beta-1,4-galactosidase, were used to digest (Fab)(2) and Fc
      fragments. Binding capacity of IgG RF from patients with RA, systemic lupus
      erythematosus (SLE), and from healthy subjects to (Fab)(2) and Fc treated with
      glycosidase, was measured with immunoassay. RESULTS: Treating (Fab)(2) and Fc
      with PNGase significantly diminished their binding capacity to IgG RFs.
      Degalactosylated (Fab)(2) revealed higher affinity to IgG RF in all tested
      groups. Fc lacking terminal galactose on oligosaccharide chains showed elevated
      binding with synovial IgG RF of RA patients. However, lesser binding was observed
      in sera of patients with RA and SLE. CONCLUSIONS: Our data suggest that IgG
      molecules containing less terminal galactose on their oligosaccharide moieties
      are preferentially recognized by IgG RF. Furthermore, IgG RF display alternative
      binding specificity to degalactosylated (Fab)(2) and Fc in synovial fluids and
      sera of RA patients.

PMID- 12505100
TI  - Thymectomy in myasthenia gravis: response, complications, and associated
      conditions.
AB  - BACKGROUND: Thymectomy is considered the most effective treatment for achieving
      sustained improvement as well as remission in patients with myasthenia gravis
      (MG), and most neurologists favor the use of this procedure. The main focus of
      many current studies is to determine response-predicting factors. METHODS:
      Clinical records of 152 patients with an established diagnosis of MG who
      underwent thymectomy at our institution were reviewed. The purpose was to
      evaluate outcome of surgical management for MG and prognostic factors that
      influence that outcome. RESULTS: The majority of patients were women (119 of
      152); mean age was 32.10 +/- 14.42 years, while time elapsed from diagnosis to
      surgery was 20.67 +/- 19.7 months. Transsternal thymectomy was performed on 113
      patients and transcervical on 39. Forty percent of patients achieved remission
      and 28% showed improvement; with this, a good response to thymectomy was seen in
      68% of patients (n = 103). The most important variables associated with remission
      were <60 years of age, <2 years of preoperative symptoms, and use of
      pyridostigmine at low doses. Factors related with poor response were >60 years of
      age, preoperative Osserman stage other than II, use of high doses of
      pyridostigmine, use of corticosteroids, and presence of thymic atrophy or thymoma
      in histopathologic analyses. There was no mortality, although 20 patients (13%)
      presented complications. CONCLUSIONS: Mexican patients with MG undergoing
      thymectomies show improvement and remission rates similar to those reported by
      other studies. Age, length of symptoms, thymic pathology, and medications appear
      to be predictors of response to thymectomy for MG.

PMID- 12505101
TI  - Depression and anxiety in hyperthyroidism.
AB  - BACKGROUND: Our objective was to determine symptomatology of depression and
      anxiety in patients with untreated hyperthyroidism and compare with euthyroid
      patients. METHODS: Thirty-two patients with hyperthyroidism (high free T3 and
      free T4, and suppressed TSH) and 30 euthyroid (normal free T3, free T4, and TSH)
      controls attending the Endocrinology Out-Patient Department at Celal Bayar
      University Hospital in Manisa, Turkey were included in the study. Hormonal
      screening was performed by immunoassay and hemagglutination method. For
      psychiatric assessment, Hospital Anxiety and Depression Scale [HAD], Hamilton
      Depression Rating Scale [HAM-D], and Hamilton Anxiety Rating Scale [HAM-A] were
      used. There was no difference between the two groups in terms of demographic
      features. RESULTS: Total scores obtained both from HAM-D and HAM-A were
      significantly greater in the hyperthyroidism group than that of the euthyroid
      group (p <0.05); there was no difference in terms of HAD. When compared in terms
      of symptomatology, early insomnia (HAM-D#6), work and activities (HAM-D#7),
      psychic anxiety (HAM-D#10), weight loss (HAM-D#16), insomnia (HAM-A#4), and
      cardiovascular symptoms (HAM-A#8) were significantly more frequent in the
      hyperthyroidism group. By Wilks lambda discriminant analysis, psychomotor
      agitation (HAM-D#9), weight loss (HAM-D#16), and insomnia (HAM-A#4) were found as
      the discriminating symptoms for the hyperthyroidism group, whereas somatic
      anxiety (HAM-A#11) and loss of interest (HAD#14) were distinguishing symptoms of
      the euthyroidism group. CONCLUSIONS: Hyperthyroidism and syndromal depression
      anxiety have overlapping features that can cause misdiagnosis during acute phase.
      For differential diagnosis, one should follow-up patients with hyperthyroidism
      with specific hormonal treatment and evaluate persisting symptoms thereafter. In
      addition to specific symptoms of hyperthyroidism, psychomotor retardation, guilt,
      muscle pain, energy loss, and fatigue seem to appear more frequently in patients
      with comorbid depression and hyperthyroidism; thus, presence of these symptoms
      should be a warning sign to nonpsychiatric professionals for the need for
      psychiatric consultation.

PMID- 12505102
TI  - Predictive value of higher plasma interleukin-6 levels in patients with febrile
      neutropenia.
AB  - BACKGROUND: Patients with febrile neutropenia require hospitalization and prompt
      empirical treatment with broad-spectrum antibiotics. Patients experiencing severe
      febrile neutropenia episodes need a longer hospitalization period and close
      follow-up, but those with mild episodes might derive limited benefit from a
      lengthy hospital stay. This study investigated whether plasma interleukin-6 (IL
      6) level has a predictive value in prognosis of febrile neutropenia. METHODS:
      Twenty-six patients with various hematologic malignancies with 31 neutropenia
      episodes were enrolled in the study. Fever developed in 26 patients, 14
      clinically severe. RESULTS: Median plasma IL-6 and serum C-reactive protein (CRP)
      levels obtained during the first day of febrile episodes were found significantly
      higher in severe febrile neutropenia episodes compared to mild episodes (median
      IL-6: 92.5 pg/mL [range 40.0-650.0] vs. 23.3 pg/mL [range 15.0-65.0], p <0.00001;
      median CRP: 48 mg/dL [range 16-96] vs. 24 mg/dL [range 16-48, p = 0.0]).
      CONCLUSIONS: Plasma IL-6 levels may guide to management of febrile neutropenic
      patients and may be used as predictive factor for poor outcome in these patients.

PMID- 12505103
TI  - Quetiapine is not associated with increase in prolactin secretion in contrast to
      haloperidol.
AB  - BACKGROUND: Typical antipsychotic drugs frequently cause hyperprolactinemia and
      even galactorrhea. In addition, these side effects may result in noncompliance
      with antipsychotic treatment. Capacity to avoid hyperprolactinemia has been
      accepted as one atypical criterion. The aim of the present study was to compare
      effects of haloperidol, the most commonly used antipsychotic, and quetiapine, a
      novel antipsychotic agent used in Turkey, on serum prolactin (PRL) levels.
      METHODS: The study consisted of 35 females diagnosed with schizophrenia according
      to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) ed. (DSM-IV).
      Thirty-five patients in a drug-free period for at least 2 weeks were included to
      randomized quetiapine (n = 18) and haloperidol (n = 17) treatment group. All
      patients were assessed by Brief psychiatric rating scale (BPRS), Positive and
      negative syndrome scale (PANSS), and Extrapyramidal symptoms rating scale (ESRS).
      PRL levels were measured both at the beginning and at the sixth week of the
      study. RESULTS: Both treatment groups exhibited significant improvements in
      clinical signs as evaluated by BPRS and PANSS. While there was no significant
      difference in PRL level between groups at the beginning of the study, control
      prolactin (PRL) levels were significantly lower in quetiapine compared to
      haloperidol group. While no quetiapine group patients exhibited galactorrhea, we
      observed that two patients from the haloperidol group had galactorrhea related to
      hyperprolactinemia. CONCLUSIONS: The present study revealed that quetiapine is
      not associated with increase in PRL secretion in contrast to the conventional
      antipsychotic haloperidol.

PMID- 12505104
TI  - Detection of hepatitis B virus in seropositive and seronegative patients with
      chronic liver disease using DNA amplification by PCR.
AB  - BACKGROUND: The aim of this study was to detect DNA of hepatitis B virus (HBV)
      for reliable diagnosis of HBV infection in sera by means of a validated
      polymerase chain reaction (PCR) using a 5' oligonucleotide (primer) previously
      described and a 3' primer designed by our investigation group. METHODS: Sera
      samples collected from patients with chronic liver disease (CLD) related to HBV
      infection and negative to hepatitis C virus (HCV) infection were analyzed.
      Patients were both positive and negative to HBV by serum markers detected by
      ELISA immunoassay. A 146-base pair (bp) fragment was amplified from highly
      conserved precore-core region. This procedure enabled us to search for DNA HBV
      positive cases. RESULTS: Viral replicative state in negative hepatitis B e
      antigen (HBeAg) (15.7%) cases was verified by PCR technique. This detected
      infection by HBV in 100% of immunoassay-positive samples. Additionally, sequences
      of expected size in patients bearing atypical markers in their sera (7.1%) and
      those with negative serology (4.8%) for HBV markers were detected. CONCLUSIONS:
      In this study we have improved a PCR technique successfully applied in hepatitis
      B prevalence studies in northeastern Mexico. Prevalence of hepatitis B in this
      region of Mexico is intermediate compared to countries of the northern hemisphere
      where prevalence is lower, and to countries of Southeast Asia and the
      Mediterranean region where it is highly endemic.

PMID- 12505105
TI  - A cost-effectiveness clinical decision analysis model for treatment of
      Schizophrenia.
AB  - BACKGROUND: Schizophrenia afflicts approximately 0.7% of Mexican citizens during
      their lifetime. This study explored whether the difference in clinical efficacy
      and safety between atypical antipsychotics and conventional neuroleptics results
      in decreases in use and cost of medical services in Mexico, offsetting the higher
      price of atypical antipsychotics. METHODS: A U.S. decision analytic Markov model
      was adapted for use in Mexico to determine cost-effectiveness of treatments and
      outcomes that Mexican patients with schizophrenia may experience over a 5-year
      period when treated with olanzapine, haloperidol, or risperidone. Model parameter
      estimates were based on clinical trial data, published medical literature, and
      where needed, clinician judgment. Direct medical costs were incorporated into the
      model and outcomes were estimated using lack of relapse and clinical outcomes
      based on the Brief Psychiatric Rating Scale (BPRS) as effectiveness indicators.
      All costs are reported in Mexican pesos. RESULTS: Over a 5-year period, the cost
      of treating schizophrenia ranged from 196,620 pesos per patient initiating
      therapy with haloperidol to 226,670 pesos per patient beginning therapy with
      risperidone. Olanzapine was estimated to have slightly better non-relapse and
      BPRS-based effectiveness outcomes, but comparative total medical costs compared
      to risperidone. Patients receiving olanzapine experienced 13 and 2% fewer
      relapses compared with patients on haloperidol and risperidone, respectively. The
      5-year incremental cost-effectiveness ratio of olanzapine compared with
      haloperidol was 52,740 pesos per improved patient, BPRS-based outcome and 212,540
      pesos per avoided relapse. Sensitivity analyses indicated the model was sensitive
      only to changes in drug costs. CONCLUSIONS: Compared with haloperidol, olanzapine
      therapy results in improved symptoms, fewer relapses, and is cost-effective, even
      with conservative values for key model parameters. Olanzapine results in slightly
      improved patient outcomes and comparable costs compared with risperidone.

PMID- 12505106
TI  - Detection of organic acidemias in Brazil.
AB  - BACKGROUND: Organic acidurias or organic acidemias are inherited metabolic
      disorders in which organic acids (carboxylic acids) accumulate in tissues and
      physiologic fluids of affected individuals. They are considered the most frequent
      metabolic disorders among severely ill children. Patients frequently present
      acute symptoms in early life. Metabolic acidosis and neurologic symptoms are the
      most common signs. METHODS: Urine specimens obtained from 1,926 children from
      January 1994 to July 2001 were used in analyses. Venous blood specimens were also
      collected from some patients. Samples were initially submitted to screening tests
      for detection of inborn errors of metabolism. Identification and semi
      quantitation of organic acids in urine were performed by gas chromatography or
      gas chromatography coupled to mass spectrometry using capillary column (DB-5) and
      flame ionization detection. RESULTS: Ninety three (4.8%) cases of organic
      acidemias were diagnosed among 1,926 patients investigated from January 1994 to
      July 2001. Prompt therapy was instituted after diagnosis in a considerable number
      of patients and resulted in rapid improvement in their symptomatology, distinct
      from our previous cases diagnosed abroad where patients representing index cases
      died before any measure could be taken. CONCLUSIONS: Results demonstrate the
      importance of diagnosing organic acidurias in loco in developing countries
      despite implied extra costs.

PMID- 12505107
TI  - Hypercalculia in savant syndrome: central executive failure?
AB  - BACKGROUND: The existence of outstanding cognitive talent in mentally retarded
      subjects persists as a challenge to present knowledge. We report the case of a 16
      year-old male patient with exceptional mental calculation abilities and moderate
      mental retardation. METHODS: The patient was clinically evaluated. Data from
      standard magnetic resonance imaging (MRI) and two 99mTc-ethyl cysteine dimer
      (ECD)-single photon emission computer tomography (SPECT) (in resting condition
      and performing a mental calculation task) studies were analyzed. RESULTS: Main
      neurologic findings were brachycephalia, right-side neurologic soft signs,
      obsessive personality profile, low color-word interference effect in Stroop test,
      and diffuse increased cerebral blood flow during calculation task in 99mTc-ECD
      SPECT. MRI showed anatomical temporal plane inverse asymmetry. CONCLUSIONS:
      Evidence appears to support the hypothesis that savant skill is related to
      excessive and erroneous use of cognitive processing resources instigated by
      probable failure in central executive control mechanisms.

PMID- 12505108
TI  - Cerebral cysticercosis and echinococcosis: a preoperative diagnostic dilemma.
AB  - BACKGROUND: Seven cases of neurocysticercosis and three cases of
      neuroechinococcosis with symptoms of elevated intracranial pressure requiring
      urgent neurosurgical treatment are described. No neuroradiologic procedure
      established exact diagnosis preoperatively; this was achieved by pathohistologic
      analysis of bioptic material. METHODS: Ten patients with duration of clinical
      symptoms ranging from 1 week to 1 month were operated on at the Department of
      Neurosurgery of Sestre Milosrdnice University Hospital in Zagreb, Croatia during
      the period 1988-2000. On receipt, bioptical material was examined
      pathohistologically at the Ljudevit Jurak Clinical Department of Pathology of the
      same hospital. We compared our data with facts collected by reviewing the
      pertinent literature over the past 10 years. RESULTS: The most common
      localization of parasitic cysts in our study was posterior cranial fossa, i.e.,
      subtentorial, which, according to the literature, is a rare localization. Due to
      this unusual localization, dominant clinical symptoms included elevated
      intracranial pressure, requiring urgent surgical removal of parasitic cysts.
      CONCLUSIONS: With the exception of the epidemiologic aspect, cerebral
      cysticercosis and echinococcosis are important as a true diagnostic and
      therapeutic problem. These human parasitic zoonoses are rarely diagnosed
      preoperatively despite newly developed neuroradiologic and serologic methods,
      especially in cases of primary appearance in brain when exact diagnosis reveals
      adequate surgical removal with subsequent complete recovery.

PMID- 12505109
TI  - Emerging concepts in inflammation and fibrosis.
AB  - Hepatic and pancreatic response to several insults commonly includes similar
      pathways of inflammation, fibrogenesis/regeneration, which may occur
      simultaneously and without appropriate coordination, resulting in chronic
      inflammation, scarring, and organ dysfunction. This review highlights the opinion
      of experts gathered for the Mexican Digestive Disease Week (2001) to analyze
      these molecular events with emphasis on identifying possible therapeutic
      opportunities. Inflammatory response encompasses leukocyte infiltration, favored
      by adhesion molecules of the selectin family, chemokines, integrins, and
      activated stellate cells (SC). Quiescent SC undergo activation mediated by
      mechanical stress and expression of cytokines, oxidative stress products, and
      growth factors and play a significant role in fibrosis and in reparation toward
      synthesis of extracellular matrix components. Also, hepatocytes and acinar cells
      contribute to the inflammatory and fibrotic response. Molecules that down
      regulate this response are overexpressed. Therapeutic strategies with targeting
      to such mechanisms underlying chronic hepatic and pancreatic injury are an
      emerging reality.

PMID- 12505110
TI  - Growth of thorax in genetic anemias: an index of deficit.

PMID- 12505111
TI  - Statins do not meet expectations for lowering low-density lipoprotein cholesterol
      levels when used in clinical practice.
AB  - BACKGROUND: Statins have become a mainstay in the treatment of hyperlipidemia,
      based on their potency and favorable side-effect profile. Drug choice is presumed
      to be guided by the estimated degree of low-density lipoprotein (LDL) cholesterol
      lowering required in a particular patient and the projected efficacy of any drug
      dose combination, as contained in the package inserts for each medication. We
      investigated whether these expectations were met in a clinical practice. METHODS:
      Data were analyzed for 367 hyperlipidemic patients in a preventive cardiology
      practice who were not taking statins at entry, who were given a standard statin
      dose at their first visit, and who had at least one follow-up visit on the same
      drug/dose. Expected LDL cholesterol reductions were calculated for each patient
      based on guidelines in the package inserts for each drug. RESULTS: The mean (+/
      SD) observed LDL cholesterol reduction of 26% +/- 20% was significantly less than
      expected (34% +/- 7%, P < 0.001). The ratio of observed to expected reduction was
      not different for the three statins used (atorvastatin, 0.79 +/- 0.48;
      simvastatin, 0.88 +/- 0.61; pravastatin, 0.75 +/- 0.69; P = 0.39). CONCLUSIONS:
      The use of statins in a clinical practice led to observed reductions in LDL
      cholesterol level that were significantly less than those projected by package
      insert guidelines. We believe this gap reflects the reduced patient compliance
      frequently observed in clinical practice settings, rather than any inherent
      difference in statin responsiveness of a practice versus a trial population.
      Physicians should be aware of this disparity when using statins in the clinical
      setting.

PMID- 12505112
TI  - Practical diagnostic management of patients with clinically suspected deep vein
      thrombosis by clinical probability test, compression ultrasonography, and D-dimer
      test.
AB  - PURPOSE: To evaluate a new noninvasive diagnostic strategy for ruling out deep
      vein thrombosis consisting of either a combination of low clinical probability
      and normal ultrasonography or a combination of moderate-to-high clinical
      probability, normal ultrasonography, and a normal D-dimer test. SUBJECTS AND
      METHODS: We studied 811 patients with clinically suspected deep vein thrombosis
      using a diagnostic management strategy that combined clinical probability,
      ultrasonography, and measurement of D-dimers. The primary endpoint was venous
      thromboembolism occurring during a 3-month follow-up. RESULTS: Of the 280
      patients (35%) with a low clinical probability, 30 (11%) had an abnormal initial
      ultrasonography and were treated. Of the other 250 untreated patients with low
      clinical probability and a normal ultrasonography, 5 (2%; 95% confidence interval
      [CI]: 1% to 5%) developed a nonfatal venous thromboembolism during follow-up. Of
      the 531 patients (65%) with a moderate-to-high clinical probability, 300 (56%)
      had an abnormal ultrasonography. Of the remaining 231 patients with a normal
      ultrasonography, 148 had a normal D-dimer test; none of these patients developed
      deep vein thrombosis during follow-up (0%; 95% CI: 0% to 3%). Of the 83 patients
      with an abnormal D-dimer test, 77 underwent repeat ultrasonography about 1 week
      later; none of the 64 patients with a second normal ultrasound developed
      symptomatic deep vein thrombosis during follow-up (0%; 95% CI: 0% to 6%).
      CONCLUSIONS: This management strategy, which combines clinical probability,
      ultrasonography, and D-dimer measurements, is practical and safe in ruling out
      deep vein thrombosis in patients with clinically suspected thrombosis and reduces
      the need for repeat ultrasonography.

PMID- 12505113
TI  - Coagulation factors, inflammation markers, and venous thromboembolism: the
      longitudinal investigation of thromboembolism etiology (LITE).
AB  - PURPOSE: We sought to assess prospectively whether higher levels of blood
      coagulation factors and inflammation markers are risk factors for venous
      thromboembolism. SUBJECTS AND METHODS: In two pooled population-based cohort
      studies, we measured levels of factor VII, factor VIII, von Willebrand factor,
      fibrinogen, and C-reactive protein, and white blood cell count, in samples
      obtained from 19,237 adults with no baseline history of venous thromboembolism,
      cancer, or warfarin use. The endpoint was validated venous thromboembolism during
      follow-up (median, 7.8 years). RESULTS: A total of 159 venous thromboembolism
      events occurred. Factor VIII and von Willebrand factor were linearly associated
      with increased risk of venous thromboembolism (P for trend <0.0001). As compared
      with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of
      venous thromboembolism was 2.6 (95% confidence interval [CI]: 1.6 to 4.3) for
      factor VIII levels in the highest quartile and 3.8 (95% CI: 2.0 to 7.2) for the
      highest fifth percentile. For von Willebrand factor, the hazard ratios in middle
      aged subjects were 4.6 (95% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95%
      CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th
      percentile, as compared with the lowest quartile, also conveyed a higher risk of
      venous thromboembolism (HR = 2.4; 95% CI: 1.2 to 4.8). In contrast, there was no
      association of venous thromboembolism with fibrinogen or C-reactive protein
      levels, or white cell count. CONCLUSIONS: In this prospective study, elevated
      factor VIII and von Willebrand factor levels were common, independent, and dose
      dependent risk factors for venous thromboembolism, and an elevated factor VII
      level was a possible risk factor. Venous thromboembolism, unlike arterial
      disease, was not related to inflammatory markers.

PMID- 12505114
TI  - Association of educational status with heart rate recovery: a population-based
      propensity analysis.
AB  - PURPOSE: An abnormally attenuated heart rate recovery after exercise is a
      predictor of mortality that is thought to reflect decreased parasympathetic
      activity. Lower educational level may be associated with automatic imbalance. We
      sought to assess the association of educational level with heart rate recovery.
      SUBJECTS AND METHODS: Among 5246 healthy adults from a population-based cohort
      who underwent exercise testing, 874 (17%) did not graduate from high school, 1823
      (35%) completed high school, and 2549 (49%) attended at least some college. An
      abnormal heart rate recovery was defined as a difference of </=42 beats per
      minute between the peak heart rate and that after 2 minutes of recovery.
      Propensity scores were used to account for differences by educational status.
      RESULTS: An abnormal heart rate recovery was more common among adults who did not
      graduate from high school compared with those who attended at least some college
      (50% [440/874] vs. 28% [701/2549]; odds ratio [OR]: 2.7; 95% confidence interval
      [CI]: 2.3 to 3.1; P <0.001). After using propensity scores, lower educational
      status remained associated with an abnormal heart rate recovery (OR = 1.9; 95%
      CI: 1.6 to 2.4; P <0.001). During 12-years of follow-up, there were 327 deaths.
      Poor educational status was associated with greater mortality (9% [80/874] vs. 6%
      [247/4372]; unadjusted hazard ratio [HR] = 1.9; 95% CI: 1.4 to 2.5; P <0.001).
      However, after accounting for age, sex, and heart rate recovery, educational
      status was a weaker predictor (HR = 1.3; 95% CI: 1.0 to 1.7). CONCLUSIONS:
      Educational status is independently associated with an abnormal heart rate
      recovery.

PMID- 12505115
TI  - The effects of beta-blockers on morbidity and mortality in a population-based
      cohort of 11,942 elderly patients with heart failure.
AB  - PURPOSE: Randomized trials have shown that beta-blockers prevent morbidity and
      mortality in heart failure. However, whether beta-blockers are effective in older
      patients or those with conditions that would have led to their exclusion from
      these trials remains unclear. SUBJECTS AND METHODS: The associations between beta
      blocker use and outcomes were examined in a population-based cohort of 11,942
      older (age >/=65 years) patients with incident heart failure between 1994 and
      1999. Cox proportional hazards models were used to adjust for propensity scores,
      age, sex, comorbid conditions, and other medications. RESULTS: The mean (+/- SD)
      age of the patients was 79 +/- 8 years, 5819 (49%) were men, and 2569 (22%) had
      Charlson comorbidity scores of at least 2. During follow-up (median, 21 months),
      3539 patients were hospitalized for heart failure and 6757 died. Overall, 1162
      patients received beta-blockers. After adjustment, beta-blocker use was
      associated with substantial reductions in all-cause mortality (hazard ratio [HR]
      = 0.72; 95% confidence interval [CI]: 0.65 to 0.80), mortality due to heart
      failure (HR = 0.65; 95% CI: 0.47 to 0.90), and hospitalizations for heart failure
      (HR = 0.82; 95% CI: 0.74 to 0.92). These endpoints were less frequent in patients
      treated with beta-blockers than in untreated patients in all examined subgroups.
      All doses of beta-blockers were associated with benefit, but there was a trend
      towards greater benefit in patients prescribed higher doses. CONCLUSIONS: The
      benefits of beta-blockers seen in randomized trials extend to older patients and
      to those with conditions that would have led to their exclusion from the trials.
      There is a need for a randomized trial comparing different doses of beta-blockers
      in heart failure.

PMID- 12505116
TI  - Outpatient case presentations in the conference room versus examination room:
      results from two randomized controlled trials.
AB  - PURPOSE: Ambulatory case presentations occur typically in conference rooms, and
      attending physicians often have little contact with patients. The purpose of this
      study was to examine the effects of two different ambulatory case presentation
      formats that involve attending physicians more directly. SUBJECTS AND METHODS: We
      conducted two randomized controlled trials in a community-based ambulatory
      internal medicine clinic. Participants comprised 393 adult patients, 40 house
      officers, and 14 attending physicians. In the first trial, patient encounters
      were assigned randomly to either exclusive house officer-attending physician
      conference room discussion or to house officer-attending physician conference
      room discussion plus attending physician-patient interaction. In the second
      trial, patient encounters were assigned randomly to either exclusive house
      officer-attending physician conference room discussion or to exclusive house
      officer-attending physician discussion in the examining room with the patient
      present. Patient satisfaction; attending physician contributions to teaching,
      diagnosis, and therapy; and house officer comfort and autonomy were assessed.
      RESULTS: Patient visit satisfaction and house officer assessment of attending
      physician teaching, diagnosis, and therapy were similar in the control and
      intervention groups of both trials. Patients involved in examination room
      discussions thought they were more comfortable with the discussion (mean +/- SD,
      4.3 +/- 0.9 vs. 3.4 +/- 0.9 on a one- to five-point Likert scale, P <0.001) and
      more often indicated a preference to listen to the discussion in the future than
      did the control group (86% [71/83] vs. 63% [52/83], P <0.001). Some house
      officers (11% [9/83]) but no attending physicians (0/83, P <0.001) were made
      uncomfortable by examination room presentations, and some house officers (11%
      [9/83]) thought that examination room presentations diminished their autonomy.
      CONCLUSIONS: Patients perceive that ambulatory examination room presentations are
      beneficial, whereas some house officers perceive that examination room
      presentations are associated with discomfort and diminished autonomy.

PMID- 12505117
TI  - Why is prostate cancer screening so common when the evidence is so uncertain? A
      system without negative feedback.
AB  - The degree of enthusiasm for prostate cancer screening seems high given the
      limited evidence of benefit and the well-documented harms of treatment that
      include impotence and incontinence. The purpose of this review is to understand
      the reasons for enthusiasm and positive reinforcement perceived in clinical
      decisions about whether to screen, whether to choose aggressive therapy for
      cancer, and in how to view adverse effects following therapy. We discuss a case
      of a man who must decide whether to undergo prostate-specific antigen screening
      and treatment to illustrate the kinds of reinforcement that may occur for each
      decision.Strong positive reinforcement for each decision would make screening and
      aggressive therapy appear to be successful and the correct decision even if
      prostate cancer screening and therapy were not beneficial. A physician is
      positively reinforced for recommending screening, regardless of the test result,
      because a negative result makes a patient grateful for reassurance and a positive
      result makes a patient grateful for early detection. A patient who is impotent
      and incontinent after a decision for curative treatment may attribute his
      survival to surgery and be grateful for having his cancer cured. Individual
      experience provides almost no negative feedback that early detection and
      aggressive treatment may not work. Although reinforcement operates similarly in
      other medical decisions, the example of prostate cancer provides insight into the
      strength of the forces at work because the personal harms, which are relatively
      common and dramatic, are readily discounted or explained away. Even if prostate
      cancer screening is eventually demonstrated to provide benefit for asymptomatic
      persons, it is important to appreciate the strength of forces that may act
      independently of benefit and reinforce decision makers' choices to be aggressive
      about screening and treatment. Interventions should be considered to temper
      possible overenthusiasm for screening and treatment.

PMID- 12505118
TI  - The vulnerable plaque and acute coronary syndromes.
AB  - The interaction between the vulnerable atherosclerotic plaque and thrombus
      formation, a process referred to as atherothrombosis, is the cornerstone of acute
      coronary syndromes. Advances in noninvasive imaging have helped to identify novel
      approaches to plaque stabilization, with the potential to prevent plaque rupture,
      including lifestyle modification and dietary adjustments, as well as
      pharmacologic interventions such as statins. Following an acute coronary event,
      strategies combining mechanical and pharmacologic therapies provide considerable
      advances in prevention of subsequent cardiac events. Pharmacologic strategies to
      prevent and treat thrombotic complications related to acute coronary syndromes
      have been developed to dissolve preformed thrombi and to inhibit thrombogenesis.
      These regimens focus on inhibiting thrombin, preventing thrombi generation,
      blocking the initiation of coagulation, inhibiting platelet activation, and
      increasing fibrinolysis.

PMID- 12505119
TI  - Age as a criterion for surgery in primary hyperparathyroidism.

PMID- 12505120
TI  - Adherence to statin therapy: why aren't we doing better?

PMID- 12505121
TI  - Diagnostic algorithms for deep vein thrombosis: work in progress.

PMID- 12505122
TI  - Understanding and predicting venous thromboembolism: the role of coagulation
      factors and inflammatory markers.

PMID- 12505123
TI  - Informing patients about prostate cancer screening: identifying and meeting the
      challenges while the evidence remains uncertain.

PMID- 12505124
TI  - Cases from the Osler Medical Service at Johns Hopkins University. Left atrial
      myxoma.

PMID- 12505125
TI  - Abciximab-associated pseudothrombocytopenia.

PMID- 12505126
TI  - Asymptomatic sarcoidosis presenting as massive splenomegaly.

PMID- 12505127
TI  - Aortocaval fistula due to remote gunshot wound.

PMID- 12505128
TI  - Hereditary hemorrhagic telangiectasia, idiopathic thrombocytopenic purpura, and
      chronic lymphocytic leukemia treated with rituximab.

PMID- 12505129
TI  - Diabetic ketoacidosis associated with oral salbutamol overdose.

PMID- 12505130
TI  - Infective endocarditis due to Haemophilus aphrophilus treated with levofloxacin.

PMID- 12505131
TI  - Turnover among APM members since 1971.

PMID- 12505132
TI  - Cerebral metabolism and risperidone treatment in schizophrenia.
AB  - This paper compares the metabolic changes associated with risperidone treatment
      in schizophrenia to those induced by haloperidol, as a representative typical
      neuroleptic. A group of 11 schizophrenic patients of recent onset underwent two
      [18F] fluoro-desoxi-glucose (FDG)-positron emission tomography (PET) scans at
      rest: the first one at the moment of the diagnosis, after a minimal treatment
      with haloperidol followed by wash-out, and the second one after 6 months on
      risperidone. The study also included 34 patients on chronic haloperidol for
      comparison. PET images were analyzed using Statistical Parametric Mapping
      (SPM'99) methods. The only change after treatment with risperidone with respect
      to the baseline was a slight increase in activity in the primary visual area and
      the right insula. Patients on chronic haloperidol showed increased activity in
      the motor cortex and cerebellum, as compared to both minimally treated and
      risperidone-treated patients. The pattern of metabolic changes induced by
      risperidone appears to be different from that produced by typical antipsychotics.

PMID- 12505133
TI  - Reliabilities and intercorrelations of reported and objective measures of smoking
      in patients with schizophrenia.
AB  - We examined the test-retest reliabilities of reported and objective measures of
      smoking, and the intercorrelations among these measures, in acutely psychotic
      patients with schizophrenia to determine whether severe psychiatric illness
      affects the utility of these variables. All measures demonstrated good test
      retest reliability. Objective measures of smoking were consistently
      intercorrelated and should be the preferred outcome measures in studies testing
      strategies to reduce smoking.

PMID- 12505134
TI  - Maternal separation at birth and schizophrenia--a long-term follow-up of the
      Finnish Christmas Seal Home Children.
AB  - OBJECTIVE: Problems in the early mother-infant relation pose a hypothetical risk
      factor of schizophrenia. We studied the association between very early separation
      and later development of schizophrenia or other psychoses in a unique data set.
      METHOD: The index cohort consisted of 3020 subjects born in 1945-1965 in Finland
      who were temporarily isolated from their family immediately after birth to
      adequate nursing homes due to tuberculosis in the family. The average separation
      time was 7 months. For every index subject, two reference subjects were matched
      for sex, year of birth and place of birth. The Finnish Hospital Discharge
      Register was used to identify subjects with schizophrenia and other psychoses
      arising from childhood to middle age, between January 1, 1971 and December 31,
      1998. RESULTS: The 28-year cumulative incidence of schizophrenia was 1.6% both in
      the index cohort and in the reference cohort (rate ratio 1.01, 95% CI 0.75-1.37).
      The incidences of other psychotic disorders were 1.5% and 1.3% (RR 1.11, 95% CI
      0.79-1.58), respectively. CONCLUSION: Separation at birth was not found to be
      associated with either schizophrenia or other psychotic illness. Temporary
      placement to adequate nursing homes in the first year of life is unlikely to
      increase the risk for schizophrenia or other psychoses.

PMID- 12505135
TI  - Psychosis prediction: 12-month follow up of a high-risk ("prodromal") group.
AB  - Intervention in the prodromal phase of schizophrenia and related psychoses may
      result in attenuation, delay or even prevention of the onset of psychosis in some
      individuals. However, a "prodrome" is difficult to recognise prospectively
      because of its nonspecific symptoms. This study set out to recruit and follow up
      subjects at high risk of transition to psychosis with the aim of examining the
      predictive power for psychosis onset of certain mental state and illness
      variables.Symptomatic individuals with either a family history of psychotic
      disorder, schizotypal personality disorder, subthreshold psychotic symptoms or
      brief transient psychotic symptoms were assessed and followed up monthly for 12
      months or until psychosis onset. Twenty of 49 subjects (40.8%) developed a
      psychotic disorder within 12 months. Some highly significant predictors of
      psychosis were found: long duration of prodromal symptoms, poor functioning at
      intake, low-grade psychotic symptoms, depression and disorganization. Combining
      some predictive variables yielded a strategy for psychosis prediction with good
      sensitivity (86%), specificity (91%) positive predictive value (80%) and negative
      predictive value (94%) within 6 months. This study illustrates that it is
      possible to recruit and follow up individuals at ultra high risk of developing
      psychosis within a relatively brief follow-up period. Despite low numbers some
      highly significant predictors of psychosis were found. The findings support the
      development of more specific preventive strategies targeting the prodromal phase
      for some individuals at ultra high risk of schizophrenia.

PMID- 12505136
TI  - Schizophrenia spectrum disorders and eye tracking dysfunction in singleton and
      multiplex schizophrenia families.
AB  - One line of research which is helping to unravel the genetic susceptibility to
      schizophrenia (SZ) is the analysis of eye tracking dysfunction (ETD), a
      quantifiable phenotypic marker. To investigate if such a biological marker is
      also present in singleton schizophrenia families, we examined eye tracking in
      members of singleton families (N=53) and compared it to members of multiplex
      (N=76) and nonpsychiatric families (N=71) using high resolution infrared
      oculography. The prevalence of ETD defined by gain values (eye/target velocity)
      and saccadic frequencies during smooth pursuit at 15 degrees /s did not differ
      between multiplex and singleton families in either the schizophrenic index
      patients or their relatives, but was significantly different from nonpsychotic
      families. ETD rate was higher in those relatives with compared to those without a
      diagnosis of a schizophrenia spectrum disorder. In relatives with a spectrum
      disorder, ETD appeared to be associated with traits for "sensitivity" and
      "suspiciousness". In the group of relatives from singleton families without a
      schizophrenia spectrum disorder, we still found a higher prevalence of ETD than
      in nonpsychotic families. Our results suggest that eye tracking dysfunction is a
      very sensitive biological marker for the vulnerability to schizophrenia, even in
      those cases where no psychopathological symptoms or signs are obvious. ETD in
      schizophrenia is suggested to serve as a neurophysiological type model,
      indicating a perception deficit.

PMID- 12505137
TI  - Clinical variables related to suicide attempts in schizophrenic patients: a
      retrospective study.
AB  - In this study, we investigated the possible association between clinical or
      pharmacological variables and suicidal behavior in a sample of chronic
      schizophrenia or schizoaffective disorder patients. One hundred and three
      patients with a DSM-III-R diagnosis of chronic schizophrenia or schizoaffective
      disorder were studied. The sample was subdivided in two subsamples according to
      the presence/absence of suicidal attempts lifetime. The main demographic and
      clinical variables retrospectively collected were analyzed and compared between
      the two groups. Attempters had a significantly higher rate of nicotine abuse or
      dependence (chi-square=3.900, df=1, p<0.05, Odds Ratio (O.R.)=3.4), were more
      likely to have or have had lifetime major depressive episodes (chi-square=10.258,
      df=1, p<0.002, O.R.=6.5), were more likely to have a duration of untreated
      psychosis (DUP) > or =1 year (chi-square=6.228, df=1, p<0.02, O.R.=12.5), and
      were more frequently prescribed typical antipsychotics (chi-square=3.979, df=1,
      p<0.05, O.R.=6.5) than patients without suicidal attempts lifetime. Further
      investigations on larger samples and with prospective designs are warranted,
      particularly with respect to the role of early intervention and atypical
      antipsychotic treatment in reducing suicide risk in schizophrenic patients.

PMID- 12505138
TI  - Theory of mind and the role of IQ in chronic disorganized schizophrenia.
AB  - BACKGROUND: Several studies have suggested a theory of mind (ToM) deficit in
      schizophrenic disorders. However, the role of interfering variables such as IQ,
      attention, memory, and severity of the disorder has remained ambiguous. METHODS:
      A theory of mind picture story comprising a sequencing task, a first and a second
      order false belief test, and a tactical deception test was given to a group of 23
      patients with chronic disorganized schizophrenia and to 12 healthy control
      persons. In addition, a nonsocial picture story had to be sequenced. Severity of
      the psychopathology was measured by using the brief psychiatric rating scale
      (BPRS), IQ was estimated using the 'Mehrfachwahlwortschatztest' (MWT, multiple
      choice verbal comprehension test). RESULTS: The schizophrenic group was impaired
      relative to controls on the theory of mind task, but not on the sequencing task
      of the nonsocial picture story. However, when controlled for IQ, no such
      difference was found. These findings were neither related to severity, duration,
      nor age at onset of the disorder. CONCLUSIONS: Theory of mind deficits in
      schizophrenia may be related to domain general impairments, e.g., intelligence
      and working memory load, rather than reflecting a 'genuine' compromised mental
      state attribution similar to autistic spectrum disorders. Schizophrenic patients
      may, however, rather be impaired in how and when to apply strategic social
      reasoning. Further studies to investigate the nature of social deficiency in
      schizophrenia are warranted.

PMID- 12505139
TI  - Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric
      patients.
AB  - Herpes simplex virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and
      human herpesvirus-6 (HHV-6) are viruses capable of establishing latency. All of
      these infect the CNS and have been detected in human postmortem brains.
      Toxoplasma gondii is a protozoan organism which can reactivate in the brains of
      previously infected immunocompromised individuals. To screen for the presence of
      herpesviruses and T. gondii in postmortem orbital frontal brain samples from
      patients with schizophrenia, affective disorders, and controls, we used nested
      polymerase chain reaction (n-PCR)/sequencing. We identified HHV-6B sequences in
      2/51 postmortem brain samples but no sequences from other herpesviruses. We did
      not detect sequences of T. gondii in the postmortem brains. Additional studies
      including ones directed at the sensitive detection of viral nucleic acids in
      multiple brain regions should be directed at confirming or excluding a role for
      viruses and protozoa in the etiology of these disorders.

PMID- 12505140
TI  - Hopelessness, neurocognitive function, and insight in schizophrenia: relationship
      to suicidal behavior.
AB  - Insight and hopelessness have been reported to be associated with suicidality in
      schizophrenia. In addition, there is evidence that diminished insight is
      correlated with impairment in some domains of cognitive function in
      schizophrenia. The purpose of this study was to clarify the relative importance
      for suicidality in patients with schizophrenia of hopelessness, cognitive
      dysfunction, and insight. This study included 333 patients with chronic
      schizophrenia who were prospectively studied. Insight was rated by the insight
      items from the Schedule for Affective Disorders and Schizophrenia (SADS) and the
      Hamilton Depression Rating Scale (HDRS). Positive, negative, and anxiety
      depression symptoms were measured with the Brief Psychiatric Rating Scale (BPRS).
      Cognition was assessed with a neurocognitive battery, which included measures of
      attention and psychomotor speed, verbal fluency, verbal memory, working memory,
      and executive function. Current and lifetime suicidality was prospectively
      assessed. Hopelessness, substance abuse, and greater insight were associated with
      attempted suicide and suicidal ideation. Those with a history of lifetime, but
      not current, suicidality had better function on tests of psychomotor speed and
      attention, verbal working memory, verbal fluency, verbal memory, and executive
      function. Neurocognitive measures were not significantly correlated with
      hopelessness and insight. Hopelessness was more severe in those with current and
      lifetime suicidality. A multiple regression analysis was used to predict current
      and lifetime suicidality from hopelessness, substance abuse, insight, and
      cognitive factor scores. The regression models predicting current and lifetime
      suicidality indicated that hopelessness was the most important predictor of both
      (beta=0.41, p=0.0001; and beta=0.35, p=0.01, respectively). These findings
      suggest that hopelessness, substance abuse, greater insight into illness, and
      higher cognitive function are associated with greater suicidality in chronic
      schizophrenia, but that among these, hopelessness may be the principal predictor
      of suicidality.

PMID- 12505141
TI  - Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone.
AB  - BACKGROUND: Alcohol and cannabis use disorders worsen the course of
      schizophrenia. While the typical antipsychotics are of limited value in
      controlling substance use in schizophrenic patients, previous studies suggest
      that the novel antipsychotic clozapine (CLOZ) may decrease their substance use.
      We describe a retrospective study of the effects of the novel antipsychotics
      risperidone (RISP) and clozapine on alcohol and cannabis use in patients with
      schizophrenia or schizoaffective disorder and comorbid alcohol and/or cannabis
      use disorder. METHOD: This study involved retrospective assessment of abstinence
      (cessation of alcohol and cannabis use) in 41 patients treated with either
      risperidone (n=8) or clozapine (n=33) for at least 1 year. In 32 of these 41
      patients, information was available on whether abstinence occurred during the 1
      year period. RESULTS: Abstinence rates were significantly higher in patients
      treated with clozapine than in those treated with risperidone (54% vs. 13%,
      p=0.05). The nine patients treated for at least 1 year, but excluded from the
      analysis because time of cessation of use was not known, had all stopped
      alcohol/cannabis use during clozapine treatment. DISCUSSION: While the
      limitations of this retrospective study must be recognized, the data suggest that
      comorbid patients treated with clozapine are more likely to abstain from alcohol
      and cannabis use than are those treated with risperidone. Further prospective
      studies will be required to confirm these intriguing results.

PMID- 12505142
TI  - Childhood abuse and dissociative symptoms in adult schizophrenia.
AB  - Dissociative symptoms, occurring in many psychiatric disorders including
      schizophrenia, are often preceded by traumatic experience. We hypothesized that
      various types of childhood trauma would correlate with levels of dissociative
      symptomatology in adult patients. Twenty-six patients completed the Dissociative
      Experiences Scale (DES) and the Childhood Trauma Questionnaire (CTQ).
      Dissociation was significantly correlated with emotional abuse (r=0.84, one
      tailed p<0.001), and physical abuse (r=0.55, p<0.01). We suggest that emotional
      abuse may play an important role in the etiology of dissociation in
      schizophrenia.

PMID- 12505143
TI  - A decade of debate on early intervention in psychosis: a systematic review of
      screening criteria.

PMID- 12505144
TI  - Nutmeg and psychosis.

PMID- 12505145
TI  - Augmentation of clozapine partial responders with conventional antipsychotics.

PMID- 12505146
TI  - Weight gain, serum leptin and triglyceride levels in patients with schizophrenia
      on antipsychotic treatment with quetiapine, olanzapine and haloperidol.

PMID- 12505149
TI  - Does F1-ATPase subunit gamma turn in the wrong direction?
AB  - Analyzing the direction of F1-ATPase subunit gamma rotation, its shape and non
      random distribution of surface residues, a mechanism is proposed for how gamma
      induces the closing/opening of the catalytic sites at beta/alpha interfaces: by
      keeping contact with the mobile domain of subunits beta at the 'jaw' (D386, the
      seven consecutive hydrophobic residues and D394/E395), rotating gamma works as a
      screw conveyer within the barrel of (alpha,beta)3. Mutations of the conveyer
      contacts are predicted to inhibit. Rotating wheel cartoons illustrate enzyme
      turnover and conformational changes. Steric clashes, polar interactions and also
      substrate limitations lead to specific stops. Because it is constructed as a
      stepper, gamma prevents uncoupling at high energy charge.

PMID- 12505150
TI  - Ring and zipper formation is the key to understanding the structural variety in
      all-beta proteins.
AB  - A novel structural classification of beta proteins is presented from the
      viewpoint of the ring-shaped structure and the zipper-like contact pattern, based
      on the fact that 92% and 60% of beta proteins have the ring topology and the
      zippered contact pattern, respectively. We discuss the implication of the
      unexpectedly high preference for the ring and zippered structures in connection
      with the folding process of beta proteins.

PMID- 12505151
TI  - Characterization of a new family of proteins that interact with the C-terminal
      region of the chromatin-remodeling factor CHD-3.
AB  - The two human proteins Ki-1/57 and CGI-55 have highly similar amino acid
      sequences but their functions are unknown. We analyzed them by yeast two-hybrid
      screens and found that they interact with the C-terminal region of the human
      chromatin-remodeling factor CHD-3 (chromo-helicase-DNA-binding domain protein-3).
      The interaction of CGI-55 and CHD-3 could be confirmed in vitro and in vivo by co
      immunoprecipitations from Sf9 insect cells. Mapping showed that CGI-55 interacts
      with CHD-3 via two regions at its N- and C-terminals. The CGI-55 and Ki-1/57
      mRNAs show highest expression in muscle, colon and kidney. A CGI55-GFP fusion
      protein was localized in the cytoplasm, nucleus and perinuclear regions of HeLa
      cells. These data suggest the possibility that CGI-55 and Ki-1/57 might be
      involved in nuclear functions like the remodeling of chromatin.

PMID- 12505152
TI  - The physical state of the LDL core influences the conformation of apolipoprotein
      B-100 on the lipoprotein surface.
AB  - We assessed the influence of temperature on the secondary structure of
      apolipoprotein B-100 (apoB) in normal low-density lipoprotein (N-LDL) and
      triglyceride-rich LDL (T-LDL). Gradual heating from 7 degrees C to the phase
      transition temperature of the lipoprotein core ( approximately 28 degrees C and
      approximately 15 degrees C for N-LDL and T-LDL, respectively) gradually altered
      the secondary structure of apoB, while further heating from the phase-transition
      temperature to 45 degrees C had no additional effect. Above the phase-transition
      temperature of the core, the apoBs of N-LDL and T-LDL had a similar secondary
      structure. These results indicate that the conformation of apoB on the LDL
      surface depends strongly on the physical state of the lipoprotein core, and less
      on the lipid composition of the core per se.

PMID- 12505153
TI  - Platelet-derived growth factor (PDGF)-induced chemotaxis does not require the G
      protein-coupled receptor S1P1 in murine embryonic fibroblasts and vascular smooth
      muscle cells.
AB  - Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, signals via G protein
      coupled receptors (GPCR). The prototypical S1P receptor, S1P1 (also known as EDG
      1), a Gi-linked receptor, is critical for vascular maturation during development.
      Recent work suggested that platelet-derived growth factor (PDGF)-induced cell
      migration required the S1P1 receptor, representing a novel mechanism for cross
      talk between receptor tyrosine kinases and GPCRs. Since both S1P and PDGF are
      implicated in vascular smooth muscle cell (VSMC) pathobiology and development, we
      investigated this issue in rat VSMC and in embryonic fibroblasts derived from
      S1P1 null mice. Our data suggest that the S1P1 receptor is critical for S1P
      induced, Gi-dependent migration but not for PDGF-BB-induced, receptor tyrosine
      kinase-dependent chemotaxis in VSMC. In addition, lack of S1P1 receptor in mouse
      embryonic fibroblasts did not significantly affect PDGF-induced cell migration.
      These data question the generality of the concept that S1P1 GPCR is a critical
      downstream component of PDGF-induced chemotaxis.

PMID- 12505154
TI  - Functional role of N-linked glycosylation on the rat melanin-concentrating
      hormone receptor 1.
AB  - Melanin-concentrating hormone (MCH) is known to act through two G-protein-coupled
      receptors MCHR1 and MCHR2. MCHR1 has three potential sites (Asn13, Asn16 and
      Asn23) for N-linked glycosylation in its extracellular amino-terminus which may
      modulate its reactivity. Site-directed mutagenesis of the rat MCHR1 cDNA at
      single or multiple combinations of the three potential glycosylation sites was
      used to examine the role of the putative carbohydrate chains on receptor
      activity. It was found that all three potential N-linked glycosylation sites in
      MCHR1 were glycosylated, and that N-linked glycosylation of Asn23 was necessary
      for full activity. Furthermore, disruption of all three glycosylation sites
      impaired proper expression at the cell surface and receptor activity. These data
      outline the importance of the N-linked glycosylation of the MCHR1.

PMID- 12505155
TI  - Microtubule-dependent regulation of Rho GTPases during internalisation of
      Yersinia pseudotuberculosis.
AB  - Internalisation of the human pathogen Yersinia pseudotuberculosis via interaction
      of bacterial invasin with host beta1 integrins depends on the actin cytoskeleton
      and involves Src family kinases, focal adhesion kinase, p130Crk-associated
      substrate, proline-rich tyrosine kinase 2, Rac, Arp 2/3 complex and WASP family
      members. We show here that Rho GTPases are regulated by the microtubule system
      during bacterial uptake. Interfering with microtubule organisation using
      nocodazole or paclitaxel suppressed uptake by HeLa cells. The nocodazole effect
      on microtubule depolymerisation was partially inhibited through overexpression of
      Rac, Cdc42, RhoG or RhoA and completely prevented by expression of Vav2. This
      suggests that microtubules influence Rho GTPases during invasin-mediated
      phagocytosis and in the absence of functional microtubules Vav2 can mimic their
      effect on one, or more, of the Rho family GTPases. Lastly, overexpression of p50
      dynamitin partially inhibited bacterial uptake and this effect was also blocked
      by co-expression of Vav2, thus further implicating this guanine nucleotide
      exchange factor in activating Rho GTPases for internalisation during loss of
      microtubule function.

PMID- 12505156
TI  - Functional cysteine-less subunits of the transporter associated with antigen
      processing (TAP1 and TAP2) by de novo gene assembly.
AB  - Within the adaptive immune system the transporter associated with antigen
      processing (TAP) plays a pivotal role in loading of peptides onto major
      histocompatibility (MHC) class I molecules. As a central tool to investigate the
      structure and function of the TAP complex, we created cysteine-less human TAP
      subunits by de novo gene synthesis, replacing all 19 cysteines in TAP1 and TAP2.
      After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2
      are functional with respect to adenosine triphosphate (ATP)-dependent peptide
      transport and inhibition by ICP47 from herpes simplex virus. Cysteine-less TAP1
      and TAP2 restore maturation and intracellular trafficking of MHC class I
      molecules to the cell surface.

PMID- 12505157
TI  - Pre-transmembrane sequence of Ebola glycoprotein. Interfacial hydrophobicity
      distribution and interaction with membranes.
AB  - The membrane-interacting domain that precedes the transmembrane anchor of Ebola
      glycoprotein has been characterized. This aromatic-rich region is predicted to
      bind the membrane interface adopting an alpha-helical structure. Peptides
      representing either the Ebola glycoprotein pre-transmembrane sequence, or a
      'scrambled' control with a different hydrophobic-at-interface moment, have been
      studied. Insertion into lipid monolayers, changes in intrinsic fluorescence and
      in infrared spectra demonstrated that only the wild-type peptide bound the
      interface under equilibrium conditions and adopted an alpha-helical conformation.
      The presence of the raft-associated lipid sphingomyelin did not affect membrane
      insertion, but it stimulated highly the membrane-destabilizing capacity of the
      pre-transmembrane sequence. A parallel study of the effects of the viral sequence
      and of melittin suggests that Ebola glycoprotein pre-transmembrane sequence might
      target membranes inherently prone to destabilization by lytic peptides.

PMID- 12505158
TI  - Cloning, tissue distribution and functional characterization of the chicken P2X1
      receptor.
AB  - We describe a new chicken P2X subunit that is an orthologue of the mammalian P2X1
      receptor. Functional characterization of chicken P2X1 receptors was performed
      using the amphotericin B perforated patch configuration to avoid the current run
      down observed under whole-cell patch-clamp conditions. Responses to agonists and
      to the antagonist PPADS (pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid)
      were similar to what has been described for mammalian orthologues. However, the
      antagonists suramin and NF023 were much less potent at chicken P2X1 receptors
      than at human P2X1 receptors. In embryonic tissues, transcript expression is
      predominant in lung, liver and skeletal muscle. Overlapping expression with cP2X4
      and cP2X5 subunits in several embryonic tissues, including skeletal muscle,
      indicates that the native embryonic P2X receptors could be heteromultimeric.

PMID- 12505159
TI  - Changes in the LHCI aggregation state during iron repletion in the unicellular
      red alga Rhodella violacea.
AB  - Red algae are well suited to study the effects of iron deficiency on light
      harvesting complex for photosystem I (LHCI), since they are totally devoid of
      light-harvesting complex for photosystem II (LHCII). Iron starvation results in a
      reduction of the pigment content, an increase of the fluorescence yield and a new
      emission band at 705 nm in the 77 K fluorescence emission spectra. These changes
      reflect the accumulation of uncoupled, aggregated LHCI in iron-depleted cells.
      Reconnection of LHCI to de novo synthesized reaction center I (RCI) is the first
      event, which takes place after iron addition. The changes in the aggregation
      state of LHCI are likely to occur also in brown and green algae.

PMID- 12505160
TI  - Cytokinin affinity purification and identification of a tobacco BY-2 adenosine
      kinase.
AB  - Adenosine kinase is one of the enzymes potentially responsible for the formation
      of cytokinin nucleotides in plants. Using a zeatin affinity column a 40 kDa
      protein was isolated from tobacco Bright Yellow 2 (TBY-2) and identified by mass
      spectrometry as adenosine kinase. The ligand interaction reported here can be
      disrupted by several other adenine- but not guanine-based purine derivatives. The
      observed interaction with cytokinins is discussed in view of a putative role for
      adenosine kinase in TBY-2 cytokinin metabolism. The presented results show for
      the first time a plant adenosine kinase affinity-purified to homogeneity that was
      identified by primary structure analysis.

PMID- 12505161
TI  - Endogenous RGS proteins facilitate dopamine D(2S) receptor coupling to G(alphao)
      proteins and Ca2+ responses in CHO-K1 cells.
AB  - The role of RGS proteins on dopaminergic D2S receptor (D2SR) signalling was
      investigated in Chinese hamster ovary (CHO)-K1 cells, using recombinant RGS
      protein- and PTX-insensitive G alphao proteins. Dopamine-mediated [35S]GTPgammaS
      binding was attenuated by more than 60% in CHO-K1 D2SR cells coexpressing a RGS
      protein- and PTX-insensitive G(alphao)Gly184Ser:Cys351Ile protein versus cells
      coexpressing a similar amount of PTX-insensitive G alphaoCys351Ile protein.
      Dopamine-agonist-mediated Ca2+ responses were dependent on the coexpression with
      a G alphao Cys351Ile protein and were fully abolished upon coexpression with a G
      alphaoGly184Ser:Cys351Ile protein. These results suggest that interactions
      between the G alphao protein and RGS proteins are involved in efficient D2SR
      signalling.

PMID- 12505162
TI  - MTO: the second member of a Drosophila dual copper-thionein system.
AB  - Drosophila MTO metal binding features were analyzed for comparison with MTN, the
      paralogous Drosophila metallothionein, and to classify MTO as either zinc- or
      copper-thionein. This was achieved by a combination of in vivo, in vitro and in
      silico methodologies. All the results unambiguously classified MTO as a second
      Drosophila copper-thionein, putting Drosophila forward as the only metazoan in
      which any zinc-thionein has still to be reported. Interestingly, experimental
      data only showed minor differences in the coordinative behavior of both MTs, but
      provided a characteristic spectroscopic fingerprint, revealing the possible
      binding of chloride anions in certain metal-MTO aggregates.

PMID- 12505163
TI  - Loss-of-function and residual channel activity of connexin26 mutations associated
      with non-syndromic deafness.
AB  - Connexins are the protein subunits of gap junction channels that allow a direct
      signaling pathway between networks of cells. The specific role of connexin
      channels in the homeostasis of different organs has been validated by the
      association of mutations in several human connexins with a variety of genetic
      diseases. Several connexins are present in the mammalian cochlea and at least
      four of them have been proposed as genes causing sensorineural hearing loss. We
      have started our functional analysis by selecting nine mutations in Cx26 that are
      associated with non-syndromic recessive deafness (DFNB1). We have observed that
      both human Cx26 wild-type (HCx26wt) and the F83L polymorphism, found in
      unaffected controls, generated electrical conductance between paired Xenopus
      oocytes, which was several orders of magnitude greater than that measured in
      water-injected controls. In contrast, most recessive Cx26 mutations (identified
      in DFNB1 patients) resulted in a simple loss of channel activity. In addition,
      the V37I mutation, originally identified as a polymorphism in heterozygous
      unaffected individuals, was devoid of function and thus may be pathologically
      significant. Unexpectedly, we have found that the recessive mutation V84L
      retained functional activity in both paired Xenopus oocytes and transfected HeLa
      cells. Furthermore, both the magnitude of macroscopic junctional conductance and
      its voltage-gating properties were indistinguishable from those of HCx26wt. The
      identification of functional differences of disease causing mutations may lead to
      define which permeation or gating properties of Cx26 are necessary for normal
      auditory function in humans and will be instrumental in identifying the molecular
      steps leading to DFNB1.

PMID- 12505164
TI  - Cleavage of eIF4G by HIV-1 protease: effects on translation.
AB  - We have recently reported that HIV-1 protease (PR) cleaves the initiation factor
      of translation eIF4GI [Ventoso et al., Proc. Natl. Acad. Sci. USA 98 (2001) 12966
      12971]. Here, we analyze the proteolytic activity of HIV-1 PR on eIF4GI and
      eIF4GII and its implications for the translation of mRNAs. HIV-1 PR efficiently
      cleaves eIF4GI, but not eIF4GII, in cell-free systems as well as in transfected
      mammalian cells. This specific proteolytic activity of the retroviral protease on
      eIF4GI was more selective than that observed with poliovirus 2A(pro). Despite the
      presence of an intact endogenous eIF4GII, cleavage of eIF4GI by HIV-1 PR was
      sufficient to impair drastically the translation of capped and uncapped mRNAs. In
      contrast, poliovirus IRES-driven translation was unaffected or even enhanced by
      HIV-1 PR after cleavage of eIF4GI. Further support for these in vitro results has
      been provided by the expression of HIV-1 PR in COS cells from a Gag-PR precursor.
      Our present findings suggest that eIF4GI intactness is necessary to maintain cap
      dependent translation, not only in cell-free systems but also in mammalian cells.

PMID- 12505165
TI  - Kinetic properties and structural characteristics of an unusual two-domain
      arginine kinase of the clam Corbicula japonica.
AB  - Arginine kinase (AK) from the clam Corbicula japonica is a unique enzyme in that
      it has an unusual two-domain structure with molecular mass of 80 kDa. It lacks
      two functionally important amino acid residues, Asp-62 and Arg-193, which are
      conserved in other 40 kDa AKs and are assumed to be key residues for stabilizing
      the substrate-bound structure. K m arg and Vmax values for the recombinant two
      domain AK were determined. These values were close to those of usual 40 kDa AKs,
      although Corbicula AK lacks the functionally important Asp-62 and Arg-193. Domain
      2 of Corbicula AK was separated from the two-domain enzyme and was expressed in
      Escherichia coli. Domain 2 still exhibited activity. However, kinetic parameters
      for domain 2 appeared to be slightly, but significantly, different from those of
      two-domain AK. Thus, it is likely that the formation of the contiguous dimer
      alters the kinetic properties of its constituent domains significantly.
      Comparison of K d arg and K m arg for two-domain AK and its domain 2 showed that
      the affinity of the enzyme for arginine is greater in the presence of substrate
      ATP than in its absence. Presumably this difference is correlated with the large
      structural differences in the enzyme in the presence or absence of substrate,
      namely open and closed structures. We expressed three mutants of Corbicula AK
      domain 2 (His-60 to Gly or Arg, Asp-197 to Gly), and determined their K m arg and
      Vmax values. The affinity for the substrate arginine in mutant enzymes was
      reduced considerably, accompanied by a decrease in Vmax. These results suggest
      that His-60 and Asp-197 affect the substrate binding system, and are consistent
      with the hypothesis that a hydrogen bond is formed between His-60 and Asp-197 in
      Corbicula AK as a substitute for the Asp-62 and Arg-193 bond in normal AKs.

PMID- 12505166
TI  - Conversion of 48S translation preinitiation complexes into 80S initiation
      complexes as revealed by toeprinting.
AB  - A method of analysis of translation initiation complexes by toeprinting has
      recently acquired a wide application to investigate molecular mechanisms of
      translation initiation in eukaryotes. So far, this very fruitful approach was
      used when researchers did not aim to discriminate between patterns of toeprints
      for 48S and 80S translation initiation complexes. Here, using cap-dependent and
      internal ribosomal entry site (IRES)-dependent mRNAs, we show that the toeprint
      patterns for 48S and 80S complexes are distinct whether the complexes are
      assembled in rabbit reticulocyte lysate or from fully purified individual
      components. This observation allowed us to demonstrate for the first time a delay
      in the conversion of the 48S complex into the 80S complex for beta-globin and
      encephalomyocarditis virus (EMCV) RNAs, and to assess the potential of some 80S
      antibiotics to block polypeptide elongation. Besides, additional selection of the
      authentic initiation codon among three consecutive AUGs that follow the EMCV IRES
      was revealed at steps subsequent to the location of the initiation codon by the
      40S ribosomal subunit.

PMID- 12505167
TI  - Different heat shock protein 60 species share pro-inflammatory activity but not
      binding sites on macrophages.
AB  - In a study of seven different hsp60 species, we found that all mammalian and
      microbial proteins shared the property of eliciting an inflammatory response in
      mouse macrophages. In all cases, TNFalpha production was induced by 0.1 microM
      concentrations of hsp60. However, the different hsp60 preparations did not
      compete for the same binding site. The binding of fluorescence-labeled human
      hsp60 was inhibited by excess unlabeled human, rat or mouse hsp60, but not
      hamster, Escherichia coli, Chlamydia pneumoniae or Mycobacterium bovis hsp60. We
      conclude that phylogenetically separate hsp60 species interact with innate immune
      cells via different recognition pathways.

PMID- 12505168
TI  - Gene expression monitoring accurately predicts medulloblastoma positive and
      negative clinical outcomes.
AB  - Prediction of medulloblastoma clinical outcome is crucial to personalizing
      treatment, both to identify high-risk patients for aggressive or alternative
      therapy and to spare those at low risk from excessive treatment. The best
      predictors [Pomeroy et al. (2002) Nature 415, 436-442], based on gene expression
      monitoring at diagnosis, have shown much less accuracy in recognizing patients
      with eventual failed outcomes - <50% for the predictor making fewest total errors
      - than those who would survive, while a single gene predictor exhibited reverse
      asymmetry. Such inaccuracy in recognizing one of the outcomes is a problem for
      clinical use. We hypothesized that a non-linear model could be built to
      significantly improve prediction of medulloblastoma outcome, thereby promoting
      use of gene-expression-based predictors in a clinical setting. In fact, this
      approach resulted in fewer errors and much less asymmetry in prediction, and
      bidirectional accuracy of about 80% could be obtained via its combination with
      other methods. Indeed, three combinations of methods were identified that yielded
      significantly better predictions of clinical outcome than previously attained,
      making feasible predictors of medulloblastoma treatment response with greatly
      improved bidirectional accuracy essential for clinical use.

PMID- 12505169
TI  - Engineering of Escherichia coli beta-galactosidase for solvent display of a
      functional scFv antibody fragment.
AB  - Protein engineering allows the generation of hybrid polypeptides with functional
      domains from different origins and therefore exhibiting new biological
      properties. We have explored several permissive sites in Escherichia coli beta
      galactosidase to generate functional hybrid enzymes displaying a mouse scFv
      antibody fragment. When this segment was placed at the amino-terminus of the
      enzyme, the whole fusion protein was stable, maintained its specific activity and
      interacted specifically with the target antigen, a main antigenic determinant of
      foot-and-mouth disease virus. In addition, the antigen-targeted enzyme was
      enzymatically active when bound to the antigen and therefore useful as a reagent
      in single-step immunoassays. These results prove the flexibility of E. coli beta
      galactosidase as a carrier for large-sized functional domains with binding
      properties and prompt the further exploration of the biotechnological
      applicability of the scFv enzyme targeting principle for diagnosis or other
      biomedical applications involving antigen tagging.

PMID- 12505170
TI  - Interdomain interaction through helices A and B of DnaK peptide binding domain.
AB  - In order to better define the structural elements involved in allosteric
      signalling, wild-type DnaK and three deletion mutants of the peptide binding
      domain have been characterized by biophysical (steady-state and time-resolved
      fluorescence) and biochemical methods. In the presence of ATP the chemical
      environment of the single tryptophan residue of DnaK, located in the ATPase
      domain, becomes less polar, as seen by a blue shift of the emission maximum and a
      shortening of the fluorescence lifetime, and its accessibility to polar quenchers
      is drastically reduced. These nucleotide-dependent modifications are also
      observed for the deletion mutant DnaK1-537, but not for DnaK1-507 or DnaK1-385,
      and thus rely on the presence of residues 507-537 (helices A and the N-terminal
      half of B) of the peptide binding domain. These data indicate that alphaA and
      half alphaB contribute to the allosteric communication of DnaK. In the presence
      of ATP, they promote a conformational change that displaces a residue(s) of the
      peptide binding domain towards a region of the ATPase domain where the tryptophan
      residue (W102) is located. A putative role for these helical segments as
      regulators of the position of the lid is discussed.

PMID- 12505171
TI  - HmCRIP, a cysteine-rich intestinal protein, is expressed by an identified
      regenerating nerve cell.
AB  - A Hirudo medicinalis cDNA isolated from regenerating CNS tissue at 24 h post
      axotomy was identified as a leech homologue of the mammalian cysteine-rich
      intestinal proteins (CRIPs) and named HmCRIP. HmCRIP is up-regulated within 6 h
      of axotomy, peaking at 24 h. This is the first demonstration of a CRIP homologue
      in regenerating CNS and in a serotonergic neurone. In rodents CRIP is an
      important factor in the regulation of the inflammatory immune response through
      control of Th1/Th2 differentiation. The role of HmCRIP in the regeneration
      competent environment of the annelid central nervous system is discussed.

PMID- 12505172
TI  - Influence of environment structure and food availability on the foraging
      behaviour of the laboratory rat.
AB  - According to the optimal foraging theory, an animal is expected to enter into a
      given activity depending on associated costs and benefits. In line with this
      assumption, numerous studies have suggested that energetic reward is balanced by
      predation risk in foraging decisions. Therefore, the use of information about
      indirect cues of predation risk such as physical structure (e.g. cover, escape
      substrate) can give individuals a selective advantage. We studied foraging
      behaviour in the laboratory rat in an experimental maze; it allowed us to vary
      two environmental parameters: food availability and physical structure. In a
      first experiment, rats were offered a choice between two areas only differing in
      cover density. In a second experiment, the two areas only differed in food
      density. In a third experiment, we crossed both parameters. Our results showed
      that high "cover" patch was preferentially exploited (experiment 1) and that rats
      foraged more in the high food density patch (experiment 2). The last experiment
      showed that rats partially trade-off between cover density and food availability,
      even if the safest area was still preferred. Therefore, we suggest that foraging
      decisions depend primarily on safety needs, rather than food availability, at
      least when animals are not severely food-deprived.

PMID- 12505173
TI  - Transitions between cooperative and non-cooperative responding in the 'Pigeon's
      Dilemma'
AB  - Two pigeons played Iterated Prisoner's Dilemma (IPD) against a simulated opponent
      pre-programmed to play 'Tit-For-Tat' (TFT) and 'Random' (RND) strategies. Each
      pigeon received differential amounts of access to food following choices of
      either 'cooperate' or 'defect' on a trial. After 1000 trials against TFT and 500
      trials against RND, results indicated that choice allocation was optimal when the
      birds played against RND but was sub-optimal when the birds played against TFT.
      In order to determine why the pigeons responded suboptimally against TFT, a trial
      by-trial analysis of the data was conducted. The analysis revealed that once a
      pigeon had received the 'Sucker's' payoff (S), it was more likely to defect and
      receive the 'Temptation' payoff (T) than to cooperate and receive the 'Reward'
      (R) payoff. Local reinforcement contingencies appear to determine suboptimal
      responding against TFT in the iterated Pigeon's Dilemma.

PMID- 12505174
TI  - Play and the evolution of fairness: a game theory model.
AB  - Bekoff [J. Consci. Stud. 8 (2001) 81] argued that mammalian social play is a
      useful behavioral phenotype on which to concentrate in order to learn more about
      the evolution of fairness. Here, we build a game theoretical model designed to
      formalize some of the ideas laid out by Bekoff, and to examine whether 'fair'
      strategies can in fact be evolutionarily stable. The models we present examine
      fairness at two different developmental stages during an individual's ontogeny,
      and hence we create four strategies-fair at time 1/fair at time 2, not fair at
      time 1/not fair at time 2, fair at time 1/not fair at time 2, not fair at time
      1/fair at time 2. Our results suggest that when considering species where
      fairness can be expressed during two different developmental stages, acting
      fairly should be more common than never acting fairly. In addition, when no one
      strategy was evolutionarily stable, we found that all four strategies we model
      can coexist at evolutionary equilibrium. Even in the absence of an overwhelming
      database from which to test our model, the general predictions we make have
      significant implications for the evolution of fairness.

PMID- 12505175
TI  - Matching unrelated stimuli with same discriminative functions: training order
      effects.
AB  - Previous research has shown that after training simple discriminations (A1+/A2-,
      B1+/B2-), bringing these tasks under conditional control (J1-A1, J2-A2) leads to
      transfer of discriminative control (J1+/J2-) and to generalized matching on the
      basis of same discriminative functions (e.g. J1-B1, J2-B2). The same occurs when
      conditional discriminations are trained (D1-E1, D2-E2; F1-G1, F2-G2). When the
      subjects are then trained to demonstrate correct relations (D1-E1, D2-E2) when
      given X1 and to demonstrate incorrect relations when given X2 (XD-E), transfer of
      discriminative control (X1+/X2-) and generalized matching on the basis of same
      discriminative functions emerges (e.g. X1F1-G1, X2F1-G2). The present study
      investigated if these performances are dependent on the training and/or testing
      order. In Experiment 1, the lower-order contingency tasks were trained before the
      higher-order contingency tasks (A1+/A2-, B1+/B2- before J-A, and D-E, F-G before
      XD-E). Half the subjects received the J-B test before the more complex XF-G test
      (Condition A), while for the other subjects, this testing order was reversed
      (Condition B). Finally, all subjects received additional tests in which they were
      given the opportunity to demonstrate the discriminative properties of the J and X
      stimuli (J1+/J2-, X1+/X2-), and to match the A, J, and X stimuli with newly
      introduced stimuli of same discriminative properties (e.g. J1-POLITE, J2-RUDE).
      Experiment 2 was the same except that the training order was reversed (J-A before
      A1+/A2-, B1+/B2-, and XD-E before D-E, F-G). The results were affected by the
      training order but not by the testing order. Transfer of discriminative functions
      and generalized matching on the basis of same functions only occurred reliably
      when the lower-order contingency tasks were trained first. A stimulus-control
      account of the data is offered.

PMID- 12505176
TI  - Repeated administration of LiCl produces an unconditioned stimulus preexposure
      effect in backward excitatory CTA but not habituation of the unconditioned
      increment in neophobia.
AB  - In one experiment using conditioned taste aversion and the unconditioned stimulus
      (US) preexposure procedure, one group of rats was given LiCl exposure for 3 days,
      whereas two other groups received saline. Following this phase, all groups were
      given a novel flavour (saccharine) to drink following either LiCl (group
      preexposed and one of the control groups) or saline injections (the remaining
      control group) and the consumption of the flavour was assessed. After this
      neophobia test, the acquired saccharine aversion was evaluated. The results show
      that three LiCl injections are enough to produce a US preexposure effect on
      backward excitatory taste aversion conditioning, whereas this number of
      injections procedure does not produce habituation of the increment in neophobia,
      an unconditioned response to the LiCl. The results are discussed taking into
      account different mechanisms involved in US preexposure effect.

PMID- 12505177
TI  - Ventilatory frequency indicates visual recognition of an allopatric predator in
      nai;ve Nile tilapia.
AB  - Perceiving a possible predator may promote physiological changes to support prey
      'fight or flight'. In this case, an increase in ventilatory frequency (VF) may be
      expected, because this is a way to improve oxygen uptake for escape tasks.
      Therefore, changes in VF may be used as a behavioral tool to evaluate visual
      recognition of a predator threat. Thus, we tested the effects of predator visual
      exposure on VF in the fish Nile tilapia, Oreochromis niloticus. For this, we
      measured tilapia VF before and after the presentation of three stimuli: an
      aquarium with a harmless fish or a predator or water (control). Nile tilapia VF
      increased significantly in the group visually exposed to a predator compared with
      the other two, which were similar to each other. Hence, we conclude that Nile
      tilapia may recognize an allopatric predator; consequently VF is an effective
      tool to indicate visual recognition of predator threat in fish.

PMID- 12505179
TI  - The challenge of improving the efficacy of measles vaccine.
AB  - Despite a safe and effective measles vaccine, measles still claims an estimated
      800,000 lives per year mostly among children in developing countries. This paper
      deals with strategies to improve vaccine efficacy and prevent unnecessary deaths,
      including considerations of one dose at 9 months strategy for developing
      countries, strain of vaccine, potency and number of doses of measles vaccine.
      After more than 20 years of measles immunisation in the developing world, the
      epidemiology of measles is radically changed, and the absence of measles
      epidemics might lead to waning immunity due to less clinical and subclinical
      infections boosting the antibody level. An increasing proportion of mothers are
      vaccinated, thus transferring a lower maternal antibody level to their infants
      who will be susceptible to measles at a younger age. The strategies to limit
      nosocomial measles infection and spread of measles epidemics are reviewed. Though
      the measles elimination programmes have been very effective in the Americas, it
      seems unlikely that they will be equally effective in the rest of the world. Even
      if eradication should be possible, it might be unwise to stop measles vaccination
      because the vaccine apparently has beneficial effects and because it would make
      measles a likely weapon for bio-terrorism. If we are unlikely to get rid of
      measles and measles vaccine, it might be wise to study further some of the many
      unanswered questions regarding the long-term effects of measles and measles
      vaccination.

PMID- 12505180
TI  - Comparative vectorial efficiency of Lutzomyia evansi and Lu. longipalpis for
      transmitting Leishmania chagasi.
AB  - The infection rates and development of Leishmania chagasi in two sandfly species,
      Lutzomyia evansi and Lutzomyia longipalpis, were evaluated under natural and
      experimental conditions. Natural infection rates of Lu. evansi in San Andres de
      Sotavento (Colombia) and Montanas de Peraza (Venezuela) (0.05 and 0.2%,
      respectively) were similar to those previously recorded for this species in
      Colombia and Venezuela and for Lu. longipalpis in many foci of American Visceral
      Leishmaniasis (AVL). Both sand fly species were able to support the development
      of two Colombian strains of L. chagasi experimentally acquired from dogs,
      hamsters or membrane feeders. However, the experimental infection rates and the
      sequence of parasite development in the guts of these sand flies revealed that
      parasite colonisation, differentiation, migration and attachment were more
      frequent and uniform in Lu. longipalpis than in Lu. evansi. This is consistent
      with a more recent association between L. chagasi and Lu. evansi, and these
      results might help to explain the irregularity of AVL outbreaks in foci where Lu.
      evansi has been reported as the sole vector.

PMID- 12505181
TI  - Evaluation of LATEX/T.b.gambiense for mass screening of Trypanosoma brucei
      gambiense sleeping sickness in Central Africa.
AB  - We compared the Card Agglutination Test for Trypanosomiasis (CATT), which
      consists of lyophilized bloodstream form trypomastigotes of Trypanosoma brucei
      gambiense (T.b.g.) variable antigen type LiTat 1.3, with LATEX/T.b.g., which
      consists of a lyophilized suspension of latex particles coated with variable
      surface glycoproteins of T.b.g. variable antigen types LiTat 1.3, 1.5 and 1.6.
      This study was carried out during two mass screening surveys in 1998 in Campo, a
      sleeping sickness focus in Cameroon, with a low prevalence (0.3%) and in 1999 in
      Batangafo which belongs to the Central African focus of Ouham which has a higher
      prevalence (3%). In Campo, we compared the CATT performed on whole blood with the
      LATEX/T.b.g. on diluted blood. In Batangafo, both tests were performed on diluted
      blood. In all circumstances, the specificity of the LATEX/T.b.g. was higher than
      of CATT. The use of LATEX/T.b.g. on diluted blood instead of CATT results in an
      important decrease of workload and as a consequence, of costs related to
      parasitological examinations. In the case of Campo the workload was up to 12
      times less than when using CATT 1.3 on whole blood and the cost divided by 3. In
      Batangafo the workload was decreased by nearly 20% with the LATEX/T.b.g. Finally,
      it should be noted that in Batangafo, one of the parasitologically confirmed
      sleeping sickness patients was negative in CATT and positive in LATEX/T.b.g. and
      that the reading of the test result in LATEX/T.b.g. is easier than in CATT.

PMID- 12505182
TI  - Mucosal leishmaniasis: in situ characterization of the host inflammatory
      response, before and after treatment.
AB  - Mucosal leishmaniasis (ML) generally shows progressive tissue destruction, not
      yet fully elucidated, associated with an intense inflammatory response. To
      contribute to the understanding of this process and of how treatment interferes
      with it, we studied several anatomopathological parameters, including those
      analyzed by immunohistochemistry, such as Leishmania antigens, cells
      participating in the immune response and cytokine expression. Biopsies were taken
      from 20 patients with ML before and after treatment. A mixed Th1 and Th2 pattern
      response occurred inside ML before treatment, persist after treatment.
      Nevertheless, this mixed response was smaller than in active lesions, with
      reduced but present numbers of cells expressing TNF-alpha, IFN-gamma and IL-4 and
      sustained numbers of cells expressing IL-10. We may conclude that specific
      treatment causes a reduction of inflammatory lesions and disappearance of
      amastigote forms of Leishmania although the factors related to the pathogenesis
      of the lesion, such as T CD4+ and T CD8+ lymphocytes and Leishmania antigens,
      persist in treated lesions. The maintenance of these inflammatory patterns may be
      due to a specific host-parasite relationship response, strongly indicating the
      need for continuous surveillance of LM patients at risk of reactivation, despite
      effective cicatrization after therapy.

PMID- 12505183
TI  - Human cystic echinococcosis in Kyrgystan: an epidemiological study.
AB  - Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is an
      emerging disease in central Asia. This study examined official data on the
      incidence of CE between 1991 and 2000 and studied routine hospital records in the
      main surgical hospitals in Bishkek, Kyrgystan, between 1990 and 2000. In
      addition, a cross-sectional ultrasound study of a rural population was undertaken
      in northern Kyrgystan. The results of this study have indicated that the annual
      incidence of CE over the whole of Kyrgystan has increased from 5.4 cases per
      100,000 in 1991 to 18 cases per 100,000 in 2000. Likewise, hospital admissions in
      Bishkek, due to CE, have increased from an estimated 21 cases in 1990 to
      approximately 127 and 124 in 1998 and 1999, respectively. Similarly, paediatric
      cases have increased from 2 in 1990 to 82 in 2000. There was no obvious
      association with occupation of affected adults although a disproportionate number
      of hospital cases were registered as unemployed compared to the general
      population. Whilst there was no gender difference in hospital admissions amongst
      children, men were more likely to undergo hospital treatment than women. Fifty
      percent of cysts were recorded as hepatic cysts with forty seven percent recorded
      as pulmonary cysts. Analysis of the data suggests that the likelihood of an
      affected patient having a hepatic cyst decreased with age. The results of the
      cross-sectional study indicated that 20 of 1486 subjects (1.35%) examined by
      ultrasound had an abdominal hydatid cyst. By extrapolating the ratio of pulmonary
      to hepatic cysts recorded in the hospital population and adjusting for age it is
      possible that as much as 3.4% of the rural population may have sub-clinical CE.
      Analysis of the possible risk factors in the cross-sectional study revealed that
      subjects who had CE were less likely to use well water as their water supply than
      non-infected subjects.

PMID- 12505184
TI  - Ultrastructural observation of spermatozoa and fertilization in Schistosoma
      japonicum.
AB  - The ultrastructure of the sperm and the process of fertilization are described in
      Schistosoma japonicum. The sperm of S. japonicum has an elongated head and a
      single tail. The head measures 6.2 x 1.4 microm in average size. No acrosome is
      present. A mass of mitochondria locates in front of the nucleus. A layer of about
      100-120 peripheral microtubules is parallel with the long axis of the head under
      plasma membrane. The nucleus is dense with some electron-lucent patches. The tail
      is a single flagellum with unique axoneme, which originates from a centriole. The
      structure of axoneme includes two types: 9 x 2 + <<l>> in the main part of the
      flagellum, and 9 x 2 + 0 near the end of the flagellum. The sperm ultrastructure
      of S. japonicum is similar to that of other schistosomes, apart from the fact
      that two types of configuration coexisted in the same axoneme, and there is no
      striated root found in S. japonicum. The sperm differs distinctly from other
      Digenea. The aberrant ultrastructure of S. japonicum reflects that its evolution
      is far away from other genera in Digenea. Fertilization occurs at the posterior
      part of oviduct, in which region the oviduct wall lacks lamellae. Some cortical
      granules (CG) fuse with plasma membrane, and discharge their content on the
      surface of the fertilized ovum. The other CGs break down or degenerate in the
      cytoplasm. By the secondary mature division, the secondary oocyte finally divides
      to form a female pronucleus. During this period a male pronucleus also forms. The
      female and male pronucleus approach each other, come into contact in the central
      region and finally fuse to form a zygote. The function of CGs is discussed.

PMID- 12505185
TI  - The phenology of malaria mosquitoes in irrigated rice fields in Mali.
AB  - A field study was carried out in the large-scale rice irrigation scheme of the
      Office du Niger in Mali to investigate the relation between anopheline mosquito
      larval development and small-scale differences in irrigation practices, such as
      water level, irrigation application and irrigation frequency. The objective of
      the study was to find out if water management can be used as a tool for vector
      control to reduce the malaria transmission risk. Larvae of Anopheles gambiae
      s.s.,; the main malaria vector in the study area, developed mostly in the first 6
      weeks after transplanting the rice. During rice development, a succession of
      anopheline species was observed. This was associated with a marked decrease in
      light intensity reaching the water surface as plant height increased. Minor
      differences in water management resulted in noticeable variations in larval
      densities and species composition. A. gambiae s.s. larvae were most abundant
      during the early growing stages and almost absent in a closed rice crop. Due to
      improper drainage after harvest, A. gambiae s.s. breeding was soon re-established
      in fields where small pools of water were retained. The results suggest that
      larval mosquito habitats in the Office du Niger can be significantly reduced by
      water management, simultaneous planting and harvesting and proper drainage of
      fallow fields.

PMID- 12505186
TI  - Human cutaneous leishmaniasis due to Leishmania infantum in the Sidi Bourouis
      focus (Northern Tunisia): epidemiological study and isoenzymatic characterization
      of the parasites.
AB  - The authors report an increase of the number of case of cutaneous leishmaniasis
      in the Sidi Bourouis region community of Siliana Governorate (Tunisia), with 38
      cases diagnosed in 6 months (1st November 2000-30th April 2001), contrary to its
      usual sporadic character. The isoenzymatic identification of 15 isolated strains
      emphasizes the role of the Leishmania infantum zymodeme MON-1 as an important
      factor in the genesis of the sporadic cutaneous leishmaniasis of Northern
      Tunisia. In fact it was isolated in 6 cases while L. infantum MON-24, the usual
      agent was isolated in 9 cases.

PMID- 12505187
TI  - Tetanus complicating snakebite in northern Nigeria: clinical presentation and
      public health implications.
AB  - BACKGROUND: There is inequality in vaccination coverage, and adult farmers in
      tropical rural communities could have missed tetanus toxoid as campaigns target
      children. Snakebite is not uncommon and partly because of lack of effective
      antivenom, management in inaccessible areas could be complicated with tetanus in
      unimmunized victims. PATIENTS AND RESULTS: Four snakebite victims who developed
      tetanus were seen in northern Nigeria. Three were bitten while farming and
      patients took 10-25 days before presenting to hospital. All patients had incised
      bite sites and applied local medicinal herbs and in one case, a black 'snake'
      stone. Bites were by the cobra (Naja nigricollis) and carpet viper (Echis
      ocellatus) in the extremities and victims had swollen limbs and bleeding with
      incoagulable blood. Three of the patients were given anti-tetanus serum (ATS)
      after development of tetanus symptoms in a primary facility and only one recalled
      receipt of one dose of tetanus toxoid prior to bite. Patients had trismus,
      rigidity, backache, spasms and one had autonomic dysfunction and was managed with
      antispasmodics, ATS, wound care, antibiotics and supportive measures. Two
      patients with envenoming and severe tetanus received antivenom, but died. One of
      the two surviving patients developed osteomyelitis with prolonged hospital stay,
      while the other recovered with residual disability. CONCLUSION: Tetanus could
      follow snakebite in inaccessible rural agricultural communities with inadequate
      health care provision. Clinical presentation is typical but late and is
      confounded by snakebite complications leading to considerable morbidity and
      mortality. The cases highlight the triple problems of inadequacy, inaccessibility
      and inequality in health care and calls for measures aimed at improvement.

PMID- 12505188
TI  - Impact of kalbaishakhi storms on adult mosquito populations in Kolkata
      (Calcutta), India.
AB  - The effect of kalbaishakhi storms on the adult mosquito populations of Kolkata
      (Calcutta), India was studied in 2000-2001. It is revealed that the density of
      mosquitoes was reduced, on average by 59.6 and 10%, during the first and second
      24 h after each kalbaishakhi storms, respectively.

PMID- 12505189
TI  - CXC-chemokines KC and macrophage inflammatory protein-2 (MIP-2) synergistically
      induce leukocyte recruitment to the central nervous system in rats.
AB  - Intracisternal injection of the CXC-chemokines KC or macrophage inflammatory
      protein (MIP)-2 induced a pleocytosis in the cerebrospinal fluid (CSF) of rats in
      a dose dependent way. MIP-2 was much more potent than KC. The concurrent
      injection of both chemokines revealed a profound synergistic effect on leukocyte
      recruitment into CSF.

PMID- 12505190
TI  - Enhanced expression of B7.2 (CD86) by percutaneous sensitization with house dust
      mite antigen.
AB  - House dust mite antigen is a well-known allergen in the pathogenesis of atopic
      dermatitis (AD), a chronic relapsing inflammatory skin disease. We evaluated the
      AD model mice sensitized with house dust mite antigen and observed a Th2-dominant
      immune response. In this experiment, BALB/c mice were sensitized percutaneously
      with house dust mite antigen three times with 7 days interval after skin barrier
      disruption. A remarkable infiltration of polymorphonuclear granulocytes and
      monocytes in the cutis was observed in mice treated with this antigen, high serum
      IgE levels and IL-4 mRNA expression in local lymph node cells was also observed.
      CD19(+) B cell numbers overturned to CD4(+) helper T cells. In these mice, there
      was significant increase of B7.2 (CD86) expression on CD19(+) B cells. These
      results indicate that house dust mite antigen sensitizes BALB/c mice and skews
      their Th1/Th2 balance toward Th2.

PMID- 12505191
TI  - Involvement of the peripheral benzodiazepine receptor in the development of
      cutaneous pathology in Mrl/Lpr mice.
AB  - Mrl/Lpr mice develop inflammatory pathologies similar to human lupus
      erythematosus (LE). In that model, we showed a protective effect of different
      peripheral benzodiazepine receptor (PBR) ligands: PK 11195, Ro5-4864 and the
      newly described SSR180575 on the development of the cutaneous lesions.
      Specifically, we evidenced that a chronic treatment at 3 mg/kg per i.p. for 30
      days prevented acanthosis, hyperkeratosis and generation of dermal infiltrates as
      compared with control untreated mice. In addition, using a specific polyclonal
      anti mouse PBR antibody, we characterized PBR expression in the skin lesions, and
      we observed that PBR expression in the epidermal component was increased when
      Mrl/Lpr mice developed the pathology and diminished upon PBR ligand treatment.
      PBR expression modulation together with the protective effects of its ligands
      further reinforce the role that PBR may play in the regulation of inflammation
      processes. Provided the exact mechanism of action that accounts for PBR action in
      that process is elucidated, these data support new therapeutic applications for
      specific potent PBR ligands.

PMID- 12505192
TI  - Effect of interferon on human thymus microenvironment.
AB  - Interferon, a thymic immunostimulator, was used with the aim of assessing the
      importance of adrenergic nerve fibers (ANF) and/or AChE-positive nerve fibers
      (AChENF) in the regulation of some immunological functions in humans. Thymic
      normal control fragments and/or thymic fragments of immunostimulated patients
      were removed during surgical biopsies. Thymic slices were stained with eosin
      orange (for the recognition of microanatomical details of the microenvironment)
      and with Bodian's method for staining of nerve fibers. Histofluorescence
      microscopy was employed for staining ANF. AChENFs were detected by means of the
      direct-coloring thiocholine method. All images were submitted to quantitative
      morphometrical analysis and statistical comparisons of data. Moreover, the amount
      of proteins and noradrenaline was measured on thymic homogenates of the same
      patients. Treatment with interferon induces substantial changes in the thymic
      microenvironment, on ANF, on AChENFs and on the total amount of proteins and
      noradrenaline in thymic tissue homogenates. In conclusion immunostimulation with
      interferon induces substantial changes in the whole thymus and in its
      microenvironment, involving both sympathetic and parasympathetic nerve fibers.

PMID- 12505193
TI  - Components with potential immunosuppressive activity in lipopolysaccharide of
      laboratory Pseudomonas aeruginosa strains.
AB  - The ability of culture filtrate (CF) of two laboratory Pseudomonas aeruginosa
      strains to inhibit delayed type hypersensitivity (DTH) to non-bacterial antigen
      in CBA mice has been studied. It was shown that intraperitoneal injection of
      native CF of the strains did not affect the level of DTH. However, redox treated
      CF expressed the immunosuppressive activity. Gel filtration of redox activated CF
      through Sephadex G-200 showed that CF contains three immunosuppressive components
      differing by their molecular weight and specificity. All components contained
      lipid group and O-polysaccharide chains that indicated their lipopolysaccharide
      (LPS) nature. These experiments show that laboratory P. aeruginosa strains have
      three LPS components but not all of them display the immunosuppressive activity.

PMID- 12505194
TI  - An intracellular antigen that reacts with MO2, a monoclonal antibody to CD14, is
      expressed by human lymphocytes.
AB  - CD14, a lipopolysaccharide (LPS) receptor, is present on the surface membrane of
      phagocytic leukocytes; it is also present in a soluble form in serum. Recently
      published results confer to this molecule novel functions that are linked to T
      cell activation and to apoptosis. We report here that we have defined and
      characterized a novel lymphocyte population in human peripheral blood, a
      population that expresses an intracellular antigen detectable with MO2, a
      monoclonal antibody directed against the human CD14 molecule. This population is
      composed primarily of CD8-positive T-cells. We found surprisingly that this novel
      MO2-positive population of lymphocytes was greatly enhanced in asymptomatic,
      untreated HIV-positive individuals.

PMID- 12505195
TI  - Pyrrolidinedithiocarbamate inhibits NF-kappaB activation and IL-8 production in
      intestinal epithelial cells.
AB  - During inflammatory bowel disease and intestinal ischemia, epithelial cells of
      the gut mucosa produce various inflammatory mediators, including the chemokine
      interleukin (IL-8). This IL-8 produced by intestinal epithelial cells has
      recently been implicated as a contributory factor to the deleterious inflammatory
      process resulting in colitis during inflammatory bowel disease or multiple organ
      failure following shock and trauma. Recent evidence suggests that the
      transcription factor nuclear factor kappaB (NF-kappaB) is a central regulator of
      IL-8 gene expression. In the present paper we investigated the effect of
      pharmacological inhibition of NF-kappaB with pyrrolidinedithiocarbamate (PDTC) on
      IL-1beta-induced IL-8 production by the human intestinal epithelial cell line HT
      29. Pretreatment of cells with PDTC (3-1000 microM) dose-dependently attenuated
      IL-8 production. Furthermore, PDTC (100 microM) suppressed the accumulation of IL
      8 mRNA. PDTC inhibited the activation of NF-kappaB, because PDTC suppressed both
      NF-kappaB DNA binding and NF-kappaB-dependent transcriptional activity. Taken
      together, our data demonstrate that NF-kappaB inhibition with PDTC decreases IL-8
      production by intestinal epithelial cells.

PMID- 12505196
TI  - A role for the P1 anchor residue in the thermal stability of MHC class II
      molecule I-Ab.
AB  - The thermal stability of the murine MHC class II molecule, I-A(b), in complex
      with invariant chain-derived peptide (CLIP) and an antigenic peptide derived from
      the alpha subunit of the I-E molecule (Ealpha) at mildly acidic and neutral pH
      were analyzed using circular dichroism (CD). The stability of I-A(b)-CLIP was
      increased by a single amino acid substitution in the P1 anchor residue, from Met
      of CLIP to Phe of Ealpha, similar, in this respect, to I-A(b)-Ealpha. This
      indicates that hydrophobic interaction in the P1 pocket is critical and plays a
      primary role in the stability of the complex. The structural models of I-A(b)
      peptides based on the crystal structure of I-A(d) might explain the increased
      stability and the preference for hydrophobic residues in this site. Taken
      together with what is known of the resident stability at a mildly acidic pH, the
      difference in stability would closely correlate with the ability of MHC class II
      to exchange peptides from CLIP to antigenic peptides in the endosome.

PMID- 12505197
TI  - A role for chondroitin sulphate B in the activity of interleukin 12 in
      stimulating gamma-interferon secretion.
AB  - We show, using a murine NK cell line which responds quantitatively to rmIL-12,
      that treatment with ChABCase, but not other GAGases, results in substantial
      reductions in the secretion of gamma-IFN. Likewise, treatment of the cells with a
      beta-D-xyloside inhibitor of proteoglycan biosynthesis inhibits this cytokine
      response. In both treatments, the addition of soluble, exogenous GAGs does not
      relieve the inhibition of gamma-IFN secretion. We also demonstrate by ELISA that
      rmIL-12 binds to CS B. Overall, our studies on this in vitro cellular model of
      the initiation of Th1 immune responses indicate a major role for cell-surface,
      iduronate-rich, CS proteoglycan in the biological activity of IL-12.

PMID- 12505198
TI  - Strong association of HLA-Cw6 allele with juvenile psoriasis in Polish patients.
AB  - Association of psoriasis vulgaris with HLA-C is not equally strong in different
      human populations. It has not yet been studied in Polish patients at DNA level,
      but only by serology that is inadequate for HLA-C. Therefore, we examined the
      distribution of HLA-C alleles by means of low resolution PCR-SSP in 102 Polish
      psoriatics and 123 healthy controls. We have found significantly higher
      representation of HLA-Cw*06 (odds ratio, 18.73; P(cor)<0.001) and significantly
      lower representation of HLA-Cw*07 (odds ratio, 0.41; P(cor)<0.038) in patients
      than in controls. Association of HLA-Cw*06 with psoriasis was even stronger in
      early age at onset (0-20 years) group: odds ratio, 77.71; P(cor)<0.001.
      Therefore, our population seems to belong to those with strong association of
      psoriasis with HLA-Cw*06.

PMID- 12505199
TI  - A monoclonal antibody specific for rat IL-18BP and its application in determining
      serum IL-18BP.
AB  - IL-18 binding protein (IL-18BP) is a soluble inhibitory receptor for IL-18, a
      proinflammatory cytokine that plays a major role in IL-12-driven Th1 cell
      differentiation. IL-18BP is presumed to play a vital regulatory function in IL-18
      mediated immune responses, although its precise role in immunomodulation in
      various diseases is not well understood. In the present study, we have generated
      and characterized a mouse monoclonal antibody (2A6H11), specific for rat IL-18BP.
      Its binding epitope is within amino acids 29-60 on IL-18BP and it does not
      interfere with the function of IL-18BP. Using this monoclonal antibody, we have
      developed an ELISA for determining IL-18BP levels. We observed elevated levels of
      IL-18BP in sera of rats with experimental autoimmune myasthenia gravis (EAMG), in
      comparison with the levels in healthy rats. Thus, this monoclonal antibody can
      serve as a valuable tool to elucidate the role of IL-18BP in EAMG and in other
      rat models for autoimmune diseases.

PMID- 12505200
TI  - Evaluation of humoral response to tumor antigens using recombinant expression
      based serological mini-arrays (SMARTA).
AB  - Screening of expression cDNA libraries derived from human neoplasms with
      autologous sera (SEREX) is an established method for defining antigens
      immunogenic in individual cancer patients. Although the majority of SEREX-derived
      cDNA clones encode autoantigens, some of them represent shared cancer antigens
      with cancer-related serological profiles. Routine evaluation of multiple SEREX
      derived clones in serological assays using panels of allogeneic sera from cancer
      patients is an important step towards defining disease parameters of diagnostic
      and prognostic significance. Here we show how the seroreactivity of multiple
      SEREX-derived antigens can be simultaneously evaluated using a rapid semi
      quantitative protocol of allogeneic screening, which we call SMARTA (serological
      mini-arrays of recombinant tumor antigens).

PMID- 12505201
TI  - Toll-like receptor-4 is involved in eliciting an LPS-induced oxidative burst in
      neutrophils.
AB  - The lipopolysaccharide (LPS) receptor complex of mononuclear phagocytes is
      composed of Toll-like receptor-4 (TLR4), MD-2 and CD14. Other phagocyte
      populations may express similar LPS receptors. The transmembrane glycoprotein
      TLR4 was shown to induce or upregulate a variety of gene products, which
      collectively are the mediators of an LPS effect. In this study, an involvement of
      TLR4 in mediation of an oxidative burst was determined using murine peritoneal
      exsudate neutrophils and lucigenin-enhanced chemiluminescence (CL). The CL
      response was dependent on the LPS dose and the presence of serum, putatively a
      source of lipopolysaccharide-binding protein (LBP). In the absence of serum, a CL
      signal was elicited by 4 microg/ml LPS in peritoneal exsudate cells (PEC) from
      TLR4-sufficient (C3H/HeN) but not TLR4 deficient (C3H/HeJ) mice. The signal
      obtained in PEC from TLR4-sufficient mice was completely abrogated by superoxide
      dismutase (SOD), which indicated that the response depended on the formation of
      superoxide anion, and was also seen in purified neutrophils but not purified
      macrophages (Mphi). In the presence of serum, lower LPS concentrations (e.g. 40
      ng/ml) elicited a strong CL response in PEC from TLR4-sufficient, and a weak
      signal in cells from TLR-4-deficient mice. This suggests that TLR4 engagement is
      involved in promoting an oxidative burst in murine neutrophils.

PMID- 12505202
TI  - Association of cancer-related symptoms with physiological parameters.

PMID- 12505203
TI  - Re. Probing the paradox of patients' satisfaction with inadequate pain
      management.

PMID- 12505204
TI  - Pseudo-meningocele following apparently uncomplicated lumbar puncture--a common
      procedure with a rare complication.

PMID- 12505205
TI  - Development of a cancer pain prognostic scale.
AB  - The purpose of this study was to develop a Cancer Pain Prognostic Scale (CPPS)
      which could predict the likelihood of pain relief within 2 weeks for cancer
      patients with moderate to severe pain. Seventy-four (74) consecutive patients who
      presented with cancer-related pain were managed in accordance with the guidelines
      for pain management developed by the United States Agency for Health Care Policy
      and Research (AHCPR). Patients were followed weekly using the Brief Pain
      Inventory (BPI), and medications were recorded weekly for 3 weeks. Baseline
      scores from the Functional Assessment of Cancer Therapy (FACT-G), Mental Health
      Inventory (MHI), Karnofsky Performance Status (KPS), and Memorial Symptom
      Assessment Scale Short Form (MSAS-SF) at initial interview served as explanatory
      variables in a logistic regression model. Pain relief > or = 80% at the end of
      weeks 1 and 2 were used as outcomes in this model. From this analysis, we
      developed a predictive formula, the CPPS, which includes the worst pain severity,
      FACT-G emotional well being, daily opioid dose, and pain characteristics. The
      rule yields a numerical score that ranges from 0-17. Higher scores correspond to
      a higher probability of good pain relief. The CPPS has the potential to rapidly
      identify patients with poor pain prognosis. It can be used as a research tool to
      characterize pain in cancer patients.

PMID- 12505206
TI  - Greek McGill Pain Questionnaire: validation and utility in cancer patients.
AB  - In 1968, Melzack and Casey suggested that there are three major psychological
      dimensions of pain: sensory, affect, evaluative. These categories interact with
      one another to provide quantitative and qualitative information on the components
      of pain. In 1975, Melzack developed the McGill Pain Questionnaire, which is
      composed of four major parts and evaluates the qualities of pain. The aim of this
      study was to assess the applicability, reliability, and validity of the McGill
      Pain Questionnaire on a sample of Greek cancer patients receiving palliative
      treatment. It was administered to 114 cancer patients before the initiation of
      the palliative treatment, and then to 80 cancer patients during the treatment 7
      days later. The results indicated that scale reliability was very good (0.95
      0.97). During the pretreatment period, correlations between Present Rating Index
      (PRI), Present Pain Intensity (PPI), and Number of Words Chosen (NWC) ranged
      between 0.42 and 0.92. During the post-treatment time, the correlations ranged
      between 0.28 and 0.91. Only 21.8% of the words met a criterion of 30% for
      representativeness on the first administration of the questionnaire, and 9% met
      this criterion on the second. Validity was satisfactory (P < 0.005) according to
      "responsiveness to changes in time", as there was a statistical difference
      between the pretreatment and post-treatment time. Patients presented a desirable
      level of convergent construct validity (P < 0.05) concerning their performance
      status. Exploratory factor analysis was examined and two factors with eigenvalue
      over 1 were extracted, and they accounted for 95.2% of the variance. These
      results support the Greek-MPQ as a reliable and valid measure for evaluating the
      qualities of cancer pain in patients receiving palliative care.

PMID- 12505207
TI  - Quality of life of palliative care patients in the last two weeks of life.
AB  - Quality of life (QOL) is the main consideration in caring for advanced cancer
      patients, yet little is known about the QOL in the terminal phase. We profiled
      the QOL of 58 advanced cancer patients during their last 2 weeks of life using
      the McGill QOL questionnaire-Hong Kong version. The patients provided ratings of
      QOL an average of 5.6 (median 6) days pre-death. Palliative care services were
      successful in maintaining the total QOL score during the dying phase. The mean
      score was 7.0 of 10. Among the various domains, the physical and existential
      domains scored relatively poorly at 5.9 and 6 of 10, respectively. The worst
      physical symptom and meaning of life were the individual items with the poorest
      scores (4.8 and 5.4 of 10, respectively). Compared with admission, there was
      statistically significant improvement in the worst physical symptom (P = 0.02)
      and eating item (P = 0.002), but deterioration in physical well-being (P = 0.03),
      meaning of existence (P = 0.007), and satisfaction with oneself (P = 0.04). In
      conclusion, QOL evaluation during the terminal phase identifies important aspects
      requiring improvement during the last two weeks of life. Physical and existential
      domains of dying cancer patients needed more attention.

PMID- 12505208
TI  - Care of the dying: is pain control compromised or enhanced by continuation of the
      fentanyl transdermal patch in the dying phase?
AB  - The introduction of fentanyl transdermal patches has led to concern and confusion
      regarding the management of pain control in the dying phase. Data were collected
      retrospectively from 94 dying patients. Two groups were identified-patients
      treated with fentanyl transdermal patch who remained on the patch in the dying
      phase and patients on oral morphine who converted to a 24-hour subcutaneous
      infusion of diamorphine via a syringe driver in the dying phase. Both the
      fentanyl group and the diamorphine group had good pain control in the last 48
      hours of life. During the last 48 hours of life, the proportion of patients with
      controlled pain was statistically significant in favor of the fentanyl group in 2
      of the 12 observations undertaken, in particular whether the fentanyl transdermal
      patch should be continued or discontinued. Patients in the fentanyl group
      received fewer "as required" opioid doses compared to patients in the diamorphine
      group, although the difference was statistically significant only for the last
      day of life. This study showed that pain control was not compromised in the dying
      phase with continued use of the fentanyl patch.

PMID- 12505209
TI  - Physical function in patients with cancer: psychometric characteristics and
      clinical usefulness of a physical performance test battery.
AB  - This study investigated the psychometric properties of a battery of physical
      performance tests, characterized physical function in patients with cancer
      referred for rehabilitation, and provided normative standards against which to
      compare disease progression and/or future treatment effectiveness. A total of 109
      patients with cancer (55 women and 54 men) and 105 control subjects (66 women and
      39 men) participated. Subjects completed self-report questionnaires regarding
      pain, physical function, and fatigue, and also performed nine physical
      performance tests: the time taken to complete various tasks (picking up coins,
      tying a belt, reaching up, putting on a sock, standing from sitting, a 50-foot
      fast walk, a 50-foot walk at preferred speed), the distance walked in 6 minutes,
      and the distance reached forward while standing were measured. Inter-tester and
      test-retest reliability was good to excellent for all tests (ICC(11) 0.69 to
      0.99). Known group analyses controlling for age were significant (P < 0.001) for
      all physical performance tests. Control subjects significantly and systematically
      outperformed those with cancer by a factor of two or three. Examination of the
      correlation matrices showed relatively low correlations between performance and
      external measures (r = 0.01 to 0.45). In contrast, correlations among performance
      measures were generally in the range of r = 0.25 to 0.85. Correlations between
      self-report of function and performance of functional tests were moderate,
      suggesting that the two methods of measuring function are complementary and both
      should be used for assessment and as outcome measures.

PMID- 12505210
TI  - Relationship between pain-specific beliefs and adherence to analgesic regimens in
      Taiwanese cancer patients: a preliminary study.
AB  - This pilot cross-sectional study aimed to 1) explore pain beliefs and adherence
      to prescribed analgesics in Taiwanese cancer patients, and 2) examine how
      selected pain beliefs, pain sensory characteristics, and demographic factors
      predict analgesic adherence. Pain beliefs were measured by the Chinese version of
      Pain and Opioid Analgesic Beliefs Scale-Cancer (POABS-CA) and the Survey of Pain
      Attitudes (SOPA). Analgesic adherence was measured by patient self-report of all
      prescribed pain medicine taken during the previous 7 days. Only 66.5% of
      hospitalized cancer patients with pain (n = 194) adhered to their analgesic
      regimen. Overall, patients had relatively high mean scores in beliefs about
      disability, medications, negative effects, and pain endurance, and low scores in
      control and emotion beliefs. Medication and control beliefs significantly
      predicted analgesic adherence. Patients with higher medication beliefs and lower
      control beliefs were more likely to be adherent. Findings support the importance
      of selected pain beliefs in patients' adherence to analgesics, suggesting that
      pain beliefs be assessed and integrated into pain management and patient
      education to enhance adherence.

PMID- 12505211
TI  - The cancer anorexia-cachexia syndrome: a survey of the Prognostic Inflammatory
      and Nutritional Index (PINI) in advanced disease.
AB  - Other than weight loss, most traditional methods of nutritional assessment are
      not acceptable in advanced cancer patients because they are inaccurate, too
      expensive for routine use, or too difficult for a debilitated person to complete.
      The prognostic inflammatory and nutritional index (PINI) is a formula devised to
      evaluate nutritional status and prognosis in critically ill patients. It has been
      suggested that the PINI score can be used to follow most pathological conditions.
      It has been measured in several settings and has been found to be a reliable
      indicator of both nutritional status and prognosis in trauma, burn, infected, and
      cardiac patients. In this pilot study, we evaluated the PINI in 50 consecutive
      patients referred to a palliative care service. Compared to a value in normal,
      healthy people of <1, the mean score in this sample was 102 (SD = 142, 95% CI =
      62-142). The mean protein values were: alpha-1-acid glycoprotein 1409 mg/l (SD =
      556, 95% CI = 1251-1567); C-reactive protein (CRP) 106 mg/l (SD = 89, 95% CI = 81
      131); albumin 24 g/l (SD = 7, 95% CI = 23-26); and prealbumin 147 mg/l (SD = 73,
      95% CI = 126-168). There was no significant association between the PINI and
      corticosteroid use, weight loss over time, age, or sex. These data indicate that
      the PINI is highly abnormal in our population. The CRP may be the most important
      value.

PMID- 12505212
TI  - Phantom pain and health-related quality of life in lower limb amputees.
AB  - Amputation of a limb may affect quality of life. However, little is known
      concerning health-related quality of life in amputees. The purposes of this study
      were to describe health-related quality of life in a population of lower limb
      amputees and to investigate potential determinants, including phantom pain. Data
      from 437 patients with a lower limb amputation were analyzed in this cross
      sectional study. Amputation-related problems were investigated using a
      questionnaire. Health-related quality of life was investigated using the RAND-36
      DLV. Amputees with phantom pain had a poorer health-related quality of life than
      amputees without phantom pain. In general, the most important amputation-specific
      determinants of health-related quality of life were "walking distance" and "stump
      pain."

PMID- 12505213
TI  - A phase I study on the feasibility and acceptability of an acupuncture/hypnosis
      intervention for chronic pediatric pain.
AB  - The purpose of the present study was to conduct a Phase I investigation examining
      the feasibility and acceptability of a complementary and alternative medicine
      (CAM) package combining acupuncture and hypnosis for chronic pediatric pain.
      Thirty-three sequentially referred children (21 girls) aged 6-18 years were
      offered 6 weekly sessions consisting of individually tailored acupuncture
      treatment together with a 20-minute hypnosis session (conducted while the needles
      were in place). Parent and child ratings of pain and pain-related interferences
      in functioning, as well as child ratings of anxiety and depression, were obtained
      at pre- and post-treatment. The treatment was highly acceptable (only 2 patients
      refused; > or = 90% completed treatment) and there were no adverse effects. Both
      parents and children reported significant improvements in children's pain and
      interference following treatment. Children's anticipatory anxiety declined
      significantly across treatment sessions. Our results support the feasibility and
      acceptability of a combined acupuncture/hypnosis intervention for chronic
      pediatric pain.

PMID- 12505214
TI  - Definition of sedation for symptom relief: a systematic literature review and a
      proposal of operational criteria.
AB  - Although sedation for symptom relief in terminally ill patients has been the
      focus of recent medical studies, the interpretation of research findings is
      difficult due to the confusing terminology. To clarify the agreements and
      inconsistencies in the definitions of sedation, a systematic review was
      performed. We searched the literature through MEDLINE from 1990 to July 2001. A
      total of 7 articles met the inclusion criteria. All studies included the use of
      sedative medications or the intention to reduce patient consciousness as an
      essential element of sedation. All but one study explicitly described that the
      primary aim of sedation was symptom palliation. Three definitions stated that
      target symptoms were severe, and 4 articles reported the refractory nature of the
      distress. On the other hand, there were marked inconsistencies in the definition
      of the degree of sedation, duration, pharmacological properties of medications
      used, target symptoms, and target populations. This review suggests that sedation
      includes two core factors: the presence of severe suffering refractory to
      standard palliative management, and the use of sedative medications with the
      primary aim to relieve distress. Thus, "palliative sedation therapy" can be
      defined as "the use of sedative medications to relieve intolerable and refractory
      distress by the reduction in patient consciousness." The marked inconsistencies
      in the definition of sedation should be considered to be subcategories of
      palliative sedation therapy, and we recommend that researchers define the degree
      of sedation, duration, pharmacological properties of medications, target
      symptoms, and target populations in future studies. This clarification of
      terminology will contribute to improving the accuracy and depth of sedation
      research.

PMID- 12505215
TI  - Cardiac troponins in renal insufficiency: review and clinical implications.
AB  - Patients with renal insufficiency may have increased serum troponins even in the
      absence of clinically suspected acute myocardial ischemia. While cardiovascular
      disease is the most common cause of death in patients with renal failure, we are
      just beginning to understand the clinical meaning of serum troponin elevations.
      Serum troponin T is increased more frequently than troponin I in patients with
      renal failure, leading clinicians to question its specificity for the diagnosis
      of myocardial infarction. Many large-scale trials demonstrating the utility of
      serum troponins in predicting adverse events and in guiding therapy and
      intervention in acute coronary syndromes have excluded patients with renal
      failure. Despite persistent uncertainty about the mechanism of elevated serum
      troponins in patients with reduced renal function, data from smaller groups of
      renal failure patients have suggested that troponin elevations are associated
      with added risk, including an increase in mortality. It is possible that
      increases in serum troponin from baseline in patients with renal insufficiency
      admitted to hospital with acute coronary syndrome may signify myocardial
      necrosis. Further studies are needed to clarify this hypothesis.

PMID- 12505216
TI  - Enhanced extracellular matrix accumulation in restenosis of coronary arteries
      after stent deployment.
AB  - OBJECTIVES: The goal of this study was to evaluate the cellular and extracellular
      composition of human coronary arterial in-stent restenosis after various periods
      of time following stent deployment. BACKGROUND: Neointimal in-growth rather than
      stent recoil is thought to be important for coronary arterial in-stent
      restenosis. There is only limited data on the cellular and extracellular
      composition changes with time after stent deployment. METHODS: We analyzed 29
      coronary arterial in-stent restenotic tissue samples (14 left anterior descending
      coronary artery, 10 right coronary artery, and 5 left circumflex artery)
      retrieved by using directional coronary atherectomy from 25 patients at 0.5 to 23
      (mean, 5.7) months after deployment of Palmaz-Schatz stents employing
      histochemical and immunocytochemical techniques. RESULTS: Cell proliferation was
      low (0% to 4%). Myxoid tissue containing extracellular matrix (ECM) enriched with
      proteoglycans was found in 69% of cases and decreased over time after stenting.
      Cell-depleted areas were found in 57% of cases and increased with time after
      stenting. Versican, biglycan, perlecan, and hyaluronan were present with varying
      individual distributions in all samples. Positive transforming growth factor
      beta1 staining was found in 80% of cases. Immunostaining with alpha-smooth muscle
      actin identified the majority of cells as smooth muscle cells with occasional
      macrophages present (< or =12 cells per section). CONCLUSIONS: These data suggest
      that enhanced ECM accumulation rather than cell proliferation contribute to later
      stages of in-stent restenosis. Balloon angioplasty of in-stent restenosis may,
      therefore, fail due to ECM changes during: 1) additional stent expansion, 2)
      tissue extrusion out of the stent, or 3) tissue compression.

PMID- 12505217
TI  - Clinical restenosis after coronary stenting: perspectives from multicenter
      clinical trials.
AB  - OBJECTIVES: We sought to evaluate clinical restenosis in a large population of
      patients who had undergone coronary stent placement. BACKGROUND: One-year success
      after coronary stenting is limited mainly by restenosis of and requirement for
      repeat revascularization of the treated lesion. We studied 6,186 patients (6,219
      lesions) pooled from several recently completed coronary stent trials. Clinical
      restenosis was defined using three different definitions: target lesion
      revascularization (TLR) beyond 30 days, target vessel revascularization (TVR)
      beyond 30 days, and target vessel failure (TVF), defined as TVR, any death, or
      myocardial infarction (MI) of the target vessel territory after hospital
      discharge. RESULTS: By one year, 638 (12.2%) patients had TLR, 748 (14.3%) had
      TVR, and 848 (16.0%) had TVF, more than two-thirds higher than the rate of these
      end points at six months. The severity of angiographic restenosis (> or =50%
      follow-up diameter stenosis [DS]) in 419 of 1,437 (29%) patients undergoing
      routine angiographic follow-up correlated directly with the likelihood of TLR
      (73% vs. 26% for >70% DS compared with <60% DS). Smaller pretreatment minimum
      lumen diameter (MLD), smaller final MLD, longer stent length, diabetes mellitus,
      unstable angina, and hypertension were independent predictors of TLR. Prior MI
      and current smoking were negative predictors. CONCLUSIONS: At one year after
      stenting, most clinical restenosis reflected TLR, which was predicted by the same
      variables previously associated with an increased risk of angiographic
      restenosis. The lower absolute rate of clinical restenosis relative to
      angiographic restenosis was due to infrequent TLR in lesions with less severe
      (<60% DS) angiographic renarrowing.

PMID- 12505218
TI  - Restenosis: do we need to understand it to treat it?

PMID- 12505219
TI  - Gender-related changes in the practice and outcomes of percutaneous coronary
      interventions in Northern New England from 1994 to 1999.
AB  - OBJECTIVES: We sought to determine whether the changing practice of
      interventional cardiology has been associated with improved outcomes for women,
      and how these outcomes compare with those for men. BACKGROUND: Previous work from
      the early 1990s suggested women are at a higher risk than men for adverse
      outcomes after percutaneous coronary interventions (PCIs). From 1994 to 1999 data
      were collected on 33,666 consecutive hospital admissions for a PCI in Northern
      New England. Multivariate models were used to adjust for differences in case-mix
      across year of procedure when comparing outcomes. Direct standardization was used
      to calculate adjusted rates. RESULTS: From 1994 to 1999, the case-mix worsened
      for both women and men, although women had more co-morbidities than did men
      throughout the period. Stent use increased over time (>75% in 1999).
      Concomitantly, the need for emergency coronary artery bypass graft surgery (CABG)
      decreased significantly (p(trend) < or = 0.001; in 1999: 0.06% for women, 0.05%
      for men). Although the emergency CABG rates were higher for women at the
      beginning of the study, by the end, they were comparable (adjusted odds ratio
      1.34, 95% confidence interval 0.76 to 2.38, p = 0.315). The myocardial infarction
      (MI) rates decreased over time for both women (by 29.7%, p(trend) = 0.378) and
      men (by 37.6%, p(trend) = 0.009) and did not differ by gender. The mortality
      rates did not decrease significantly over time and were not significantly
      different between the genders (mean 1.21% for women, 1.06% for men; p = 0.096).
      CONCLUSIONS: Concurrent with the changing practice of PCI, and despite treating
      sicker patients, there have been important improvements in post-PCI CABG and MI
      rates for women, as well as for men. Unlike in earlier years, there are no longer
      significant differences in outcomes by gender.

PMID- 12505220
TI  - Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in
      unstable angina.
AB  - OBJECTIVES: We designed a study to explore the effect of glycoprotein (GP)
      IIb/IIIa blockade on the atherosclerotic plaque and distal coronary vasculature.
      BACKGROUND: Platelet GP IIb/IIIa blockers have been proven to be beneficial in
      acute ischemic syndromes. This effect has also been attributed to the prevention
      of microvascular obstruction, although the underlying mechanisms have not been
      fully defined. METHODS: Eighteen patients with unstable refractory angina
      pectoris underwent cardiac catheterization and angioplasty. Trans-stenotic and
      microvascular resistances to flow were measured at baseline, during
      hyperventilation, and after intracoronary adenosine. Measurements were repeated
      early after abciximab administration and after successful percutaneous
      transluminal coronary angioplasty. RESULTS: Hyperventilation induced an ischemic
      attack in 12 of 18 patients and increased epicardial (12.8 +/- 16.9 vs. 6.1 +/-
      6.1 mm Hg/ml per min, p < 0.05) and microvascular (9.9 +/- 7.5 vs. 6.8 +/- 5.8 mm
      Hg/ml per min, p < 0.05) coronary resistance. Abciximab had no significant effect
      on epicardial resistance, although it significantly reduced distal coronary
      resistance under all study conditions, including baseline (4.8 +/- 4.8 mm Hg/ml
      per min, p < 0.01), hyperventilation (5.1 +/- 5.4 mm Hg/ml per min, p < 0.01),
      and intracoronary adenosine (2.7 +/- 3.0 vs. 4.3 +/- 4.3 mm Hg/ml per min, p <
      0.05). The hyperventilation test became negative in all patients after abciximab
      administration. CONCLUSIONS: These observations confirm the immediate beneficial
      effects of platelet GP IIb/IIIa blockade with abciximab in acute ischemic
      syndromes and suggest that improvement of microvascular function may play a
      central role in the mechanism of action of this drug.

PMID- 12505221
TI  - Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest.
AB  - OBJECTIVES: The aim of the study was to assess the hemodynamic status of
      survivors of out-of-hospital cardiac arrest (OHCA). BACKGROUND: The global
      prognosis after successfully resuscitated patients with OHCA remains poor.
      Clinical studies describing the hemodynamic status of survivors of OHCA and its
      impact on prognosis are lacking. METHODS: Among 165 consecutive patients admitted
      after successful resuscitation from OHCA, 73 required invasive monitoring because
      of hemodynamic instability, defined as hypotension requiring vasoactive drugs,
      during the first 72 h. Clinical features and data from invasive monitoring were
      analyzed. RESULTS: Hemodynamic instability occurred at a median time of 6.8 h
      (range 4.3 to 7.3) after OHCA. The initial cardiac index (CI) and filling
      pressures were low. Then, the CI rapidly increased 24 h after the onset of OHCA,
      independent of filling pressures and inotropic agents (2.05 [1.43 to 2.90] 8 h
      vs. 3.19 l/min per m(2) [2.67 to 4.20] 24 h after OHCA; p < 0.001). Despite a
      significant improvement in CI at 24 h, a superimposed vasodilation delayed the
      discontinuation of vasoactive drugs. No improvement in CI at 24 h was noted in 14
      patients who subsequently died of multiorgan failure. Hemodynamic status was not
      predictive of the neurologic outcome. CONCLUSIONS: In survivors of OHCA,
      hemodynamic instability requiring administration of vasoactive drugs is frequent
      and appears several hours after hospital admission. It is characterized by a low
      CI that is reversible in most cases within 24 h, suggesting post-resuscitation
      myocardial dysfunction. Early death by multiorgan failure is associated with a
      persistent low CI at 24 h.

PMID- 12505222
TI  - Early statin therapy restores endothelial function in children with familial
      hypercholesterolemia.
AB  - OBJECTIVES: This study was designed to determine whether simvastatin improves
      endothelial function in children with familial hypercholesterolemia (FH).
      BACKGROUND: Endothelial function measured by flow-mediated dilation of the
      brachial artery (FMD) is used as a surrogate marker of cardiovascular disease
      (CVD). Adult studies have shown that statins reverse endothelial dysfunction and
      therefore reduce the risk for future CVD. METHODS: The study included 50 children
      with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were
      randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed
      at baseline and at 28 weeks of treatment. RESULTS: At baseline, FMD was impaired
      in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH
      group, FMD improved significantly, whereas the FMD remained unaltered in the
      placebo FH group throughout the study period (absolute increase 3.9% +/- 4.3% vs.
      1.2% +/- 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level
      similar to the non-FH controls (15.6% +/- 6.8% vs. 15.5% +/- 5.4%, p = 0.958).
      Upon treatment, the simvastatin FH group showed significant absolute reductions
      of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density
      lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%). The absolute
      change of FMD after 28 weeks of therapy was inversely correlated to changes of TC
      (r = -0.31, p < 0.05) and LDL-C (r = -0.31, p < 0.05). CONCLUSIONS: Our data show
      significant improvement of endothelial dysfunction towards normal levels after
      short-term simvastatin therapy in children with FH. These results emphasize the
      relevance of statin therapy in patients with FH at an early stage, when the
      atherosclerotic process is still reversible.

PMID- 12505223
TI  - Shifting the diagnosis and treatment of atherosclerosis to children and young
      adults: a new paradigm for the 21st century.

PMID- 12505224
TI  - Ezetimibe coadministered with simvastatin in patients with primary
      hypercholesterolemia.
AB  - OBJECTIVES: The purpose of this study was to assess the efficacy and safety of
      ezetimibe administered with simvastatin in patients with primary
      hypercholesterolemia. BACKGROUND: Despite the availability of statins, many
      patients do not achieve lipid targets. Combination therapy with lipid-lowering
      agents that act via a complementary pathway may allow additional patients to
      achieve recommended cholesterol goals. METHODS: After dietary stabilization, a 2-
      to 12-week washout period, and a 4-week, single-blind, placebo lead-in period,
      patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145
      mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized
      to one of the following 10 groups administered daily for 12 consecutive weeks:
      ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus
      simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was
      percentage reduction from baseline to end point in direct LDL-C for the pooled
      ezetimibe plus simvastatin groups versus pooled simvastatin groups. RESULTS:
      Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density
      lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with
      simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an
      incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction
      compared with pooled simvastatin alone. Coadministration of ezetimibe and
      simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%,
      and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10
      mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C
      reduction. The coadministration of ezetimibe with simvastatin was well tolerated,
      with a safety profile similar to those of simvastatin and of placebo.
      CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant
      incremental reductions in LDL-C and TG, as well as increases in HDL-C.
      Coadministration of ezetimibe with simvastatin was well tolerated and comparable
      to statin alone.

PMID- 12505225
TI  - Low-density lipoprotein lowering therapy: an analysis of the options.

PMID- 12505226
TI  - Interatrial septum pacing guided by three-dimensional intracardiac
      echocardiography.
AB  - OBJECTIVES: Currently, the interatrial septum (IAS) pacing site is indirectly
      selected by fluoroscopy and P-wave analysis. The aim of the present study was to
      develop a novel approach for IAS pacing using intracardiac echocardiography
      (ICE). BACKGROUND: Interatrial septum pacing may be beneficial for the prevention
      of paroxysmal atrial fibrillation. METHODS: Cross-sectional images are acquired
      during a pull-back of the ICE transducer from the superior vena cava into the
      inferior vena cava by an electrocardiogram- and respiration-gated technique. Both
      atria are then reconstructed using three-dimensional (3D) imaging. Using an "en
      face" view of the IAS, the desired pacing site is selected. Following lead
      placement and electrical testing, another 3D reconstruction is performed to
      verify the final lead position. RESULTS: Twelve patients were included in this
      study. The IAS pacing was achieved in all patients including six suprafossal (SF)
      and six infrafossal (IF) lead locations all confirmed by 3D imaging. The mean
      duration times of atrial lead implantation and fluoroscopy were 70 +/- 48.9 min
      and 23.7 +/- 20.6 min, respectively. The IAS pacing resulted in a significant
      reduction of the P-wave duration as compared to sinus rhythm (98.9 +/- 19.3 ms
      vs. 141.3 +/- 8.6 ms; p < 0.002). The SF pacing showed a greater reduction of the
      P-wave duration than IF pacing (59.4 +/- 6.6 ms vs. 30.2 +/- 13.6 ms; p < 0.004).
      CONCLUSIONS: Three-dimensional ICE is a feasible tool for guiding IAS pacing.

PMID- 12505227
TI  - Coronary vein balloon angioplasty for left ventricular pacemaker lead
      implantation.
AB  - OBJECTIVES: Retrospective analysis of five cases of coronary vein balloon
      angioplasty performed to allow insertion of left ventricular pacing leads.
      BACKGROUND: Coronary vein stenoses or an insufficient vessel caliber can preclude
      transvenous placement of coronary vein leads. METHODS: We compared our total
      patient population (n = 218), in whom we implanted coronary vein leads, to those
      five patients who required coronary vein angioplasty to allow lead placement.
      Standard over-the-wire coronary artery balloon angioplasty catheters were used to
      dilate the vessel to 2.5 mm (n = 3) or 3.5 mm (n = 2). RESULTS: Transvenous lead
      placement succeeds in >99% of patients. Four cases of target vein stenoses and
      one case of a vein of insufficient caliber were successfully treated by balloon
      angioplasty. There were no complications. CONCLUSIONS: Coronary vein angioplasty
      is an effective and safe technique to permit transvenous left ventricular pacing
      lead insertion in cases of target vein stenoses or insufficient target vein
      caliber.

PMID- 12505228
TI  - Electrophysiologic actions of dl-sotalol in patients with persistent atrial
      fibrillation.
AB  - OBJECTIVES: We sought to determine the electrophysiologic actions of sotalol in
      the remodeled atrium of humans. BACKGROUND: In experimental studies, sotalol has
      limited class III action in the electrically remodeled atrium and did not prevent
      atrial fibrillation (AF) induction. METHODS: We determined the effective
      refractory periods (ERPs) at three pacing cycle lengths (400, 500, and 600 ms) in
      the high right atrium (HRA) and distal coronary sinus (DCS) before and after
      intravenous infusion of dl-sotalol in 10 patients with persistent AF who
      underwent internal cardioversion. The same protocols were performed in 10 control
      subjects in sinus rhythm. RESULTS: In the HRA and DCS, the atrial ERPs at
      different drive cycle lengths were significantly shorter in patients with AF than
      in control subjects (p < 0.05). In patients with AF, the atrial ERP's adaptation
      to rate was nearly normal in the HRA, but was poor in the DCS. In both groups, dl
      sotalol significantly increased the atrial ERPs at both the HRA and DCS, as
      compared with baseline (p < 0.05). However, the prolongation of atrial ERPs was
      significantly less at a drive cycle length of 600 ms in patients with AF versus
      control subjects (p < 0.05). After infusion of dl-sotalol, the atrial ERP's
      adaptation to rate at both the HRA and DCS was poor in patients with AF, and AF
      was still easily inducible in the majority of them, but not in control subjects.
      CONCLUSIONS: The results of the present study demonstrate that the
      electrophysiologic actions of dl-sotalol are significantly attenuated in the
      chronically remodeled human atrium, and these changes might represent a probable
      explanation for the low efficacy of dl-sotalol to prevent early AF recurrence
      after electrical cardioversion.

PMID- 12505229
TI  - Myocardial scarring in asymptomatic or mildly symptomatic patients with
      hypertrophic cardiomyopathy.
AB  - OBJECTIVES: We sought to ascertain whether myocardial scarring occurs in living
      unselected patients with hypertrophic cardiomyopathy (HCM). BACKGROUND:
      Myocardial scarring is known to occur in select HCM patients, who were highly
      symptomatic prior to death or who died suddenly. The majority of HCM patients,
      however, are minimally symptomatic and have not suffered sudden death. METHODS:
      Cine and gadolinium-enhanced magnetic resonance imaging was performed in 21 HCM
      patients who were predominantly asymptomatic. Gadolinium hyperenhancement was
      assumed to represent myocardial scar, and the extent of scar was compared to left
      ventricular (LV) morphology and function. RESULTS: Scarring was present in 17
      patients (81%). Scarring occurred only in hypertrophied regions (> or =10 mm),
      was patchy with multiple foci, and predominantly involved the middle third of the
      ventricular wall. All 17 patients had scarring at the junction of the
      interventricular septum and the right ventricular (RV) free wall. On a regional
      basis, the extent of scarring correlated positively with wall thickness (r =
      0.36, p < 0.0001), and inversely with wall thickening (r = -0.21, p < 0.0001). On
      a per patient basis, the extent of scarring (mean, 8 +/- 9% of LV mass) was
      minimally related to maximum wall thickness (r = 0.40, p = 0.07) and LV mass (r =
      0.33, p = 0.15), and correlated inversely with ejection fraction (r = -0.46, p =
      0.04). CONCLUSIONS: Myocardial scarring is common in asymptomatic or mildly
      symptomatic HCM patients who have not suffered sudden death. When present,
      scarring occurs in hypertrophied regions, is consistently localized to the
      junctions of the septum and RV free wall, and correlates positively with regional
      hypertrophy and inversely with regional contraction.

PMID- 12505230
TI  - Release of matrix metalloproteinases following alcohol septal ablation in
      hypertrophic obstructive cardiomyopathy.
AB  - OBJECTIVES: This study examined plasma levels of certain matrix metalloproteinase
      (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) species before and
      after alcohol-induced myocardial infarction (MI) in patients with hypertrophic
      obstructive cardiomyopathy (HOCM). BACKGROUND: Matrix metalloproteinases
      contribute to tissue remodeling, and endogenous control of MMP activity is
      achieved by the concordant release and binding of TIMPs. Animal models of MI have
      demonstrated a role for MMP activation in myocardial remodeling. However, the
      temporal relationship of MMP and TIMP release following a controlled myocardial
      injury in humans remains unknown. METHODS: Plasma levels for the gelatinases MMP
      2 and MMP-9, and for the collagenases MMP-8 and MMP-13, as well as TIMP-1
      profiles were examined (by enzyme-linked immunosorbent assay) at baseline and
      serially up to 60 h following alcohol injection into the septal perforator artery
      in order to induce an MI in 51 patients with HOCM (age 55 +/- 2 years). RESULTS:
      Plasma creatine kinase (MB isoform), indicating myocardial injury, increased
      2,150% 18 h post-MI (p < 0.05). Plasma MMP-9 increased by over 400% and MMP-8 by
      over 100% from baseline values by 12 h post-MI (p < 0.05 vs. baseline). A similar
      temporal profile was not observed for MMP-2 and MMP-13. In addition, a
      concomitant increase in plasma TIMP-1 levels did not occur post-MI. As a result,
      MMP/TIMP stoichiometry (MMP-9/TIMP-1 ratio) increased significantly post-MI,
      suggestive of reduced TIMP-1 mediated MMP-9 inhibition, which would potentially
      enhance extracellular myocardial remodeling. CONCLUSIONS: These unique results
      demonstrated that induction of a controlled myocardial injury in humans,
      specifically through alcohol-induced MI, caused species- and time-dependent
      perturbations of MMP/TIMP stoichiometry that would facilitate myocardial
      remodeling in the early post-MI setting.

PMID- 12505231
TI  - Dysfunction of mitochondrial respiratory chain complex I in human failing
      myocardium is not due to disturbed mitochondrial gene expression.
AB  - OBJECTIVES: Activity of mitochondrial respiratory chain complexes with and
      without mitochondrially encoded subunits was assessed in failing human myocardium
      together with parameters of mitochondrial gene expression. BACKGROUND: Mutations
      and deletions in mitochondrial genome (mtDNA) sporadically accumulate in the
      aging myocardium. In experimental heart failure, they are discussed to be a
      generalized problem resulting in disturbances of mitochondrial gene expression
      and mitochondrial function. METHODS: In left ventricular specimens from 43
      explanted failing hearts and 10 donor hearts, enzyme activities of respiratory
      chain complexes, messenger ribonucleic acid (mRNA) expression of mitochondrially
      and nuclear encoded mitochondrial components (reverse transcriptase-polymerase
      chain reaction, Northern blot), undeleted wildtype mtDNA (Southern blot), and
      nuclear encoded mitochondrial transcription factor A (mtTFA) (Western blot) were
      quantified. RESULTS: Citrate synthase normalized activity of mitochondrial
      respiratory chain complex I, which contains seven mitochondrially encoded
      subunits, was decreased by 28% in terminally failing myocardium, whereas the
      activity of the exclusively nuclear encoded complex II was unchanged. However,
      the amount of intact mtDNA, the mRNA of all mitochondrially encoded subunits of
      the entire respiratory chain, the amount of mtTFA, and the enzymatic activity of
      complex III and complex IV, which also contain mitochondrially encoded subunits,
      were normal compared with donor hearts, excluding generalized disturbance of
      mitochondrial gene expression. Retrospective analysis of drug therapy before
      transplantation identified beta-blockers as one putative protection against this
      disturbance. CONCLUSIONS: In terminally failing human myocardium of patients
      receiving drug therapy, complex I depression is not caused by mtDNA damage and
      disturbed mitochondrial gene expression. The absence of mtDNA damage should
      facilitate recovery of the overloaded myocardium, if effective unloading could be
      achieved.

PMID- 12505232
TI  - Left ventricular remodeling early after aortic valve replacement: differential
      effects on diastolic function in aortic valve stenosis and aortic regurgitation.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of aortic valve
      replacement (AVR) on left ventricular (LV) function and LV remodeling, comparing
      patients with aortic valve stenosis to patients with aortic regurgitation.
      BACKGROUND: Aortic valve disease is associated with eccentric or concentric LV
      hypertrophy and changes in LV function. The relationship between LV geometry and
      LV function and the effect of LV remodeling after AVR on diastolic filling, in
      patients with aortic valve stenosis compared with aortic regurgitation, are
      largely unknown.Nineteen patients with aortic valve disease (12 aortic valve
      stenosis, 7 aortic regurgitation) were studied using magnetic resonance imaging
      to assess LV geometry and LV function before and 9 +/- 3 months after AVR. Ten
      age-matched healthy males served as control subjects. RESULTS: Before AVR, the
      ratio between left ventricular mass index (LVMI) and left ventricular end
      diastolic volume index (LVEDVI) was only increased in patients with aortic valve
      stenosis (1.37 +/- 0.16 g/ml) compared with control subjects (0.93 +/- 0.08 g/ml,
      p < 0.05). After AVR, LVMI/LVEDVI decreased significantly in aortic valve
      stenosis (to 1.15 +/- 0.14 g/ml, p < 0.0001), but increased significantly in
      aortic regurgitation (1.02 +/- 0.20 g/ml to 1.44 +/- 0.27 g/ml, p < 0.0001).
      Before AVR, diastolic filling was impaired in both aortic valve stenosis and
      aortic regurgitation. Early after AVR, diastolic filling improved in patients
      with aortic valve stenosis, whereas patients with aortic regurgitation showed a
      deterioration in diastolic filling. CONCLUSIONS: Early after AVR, patients with
      aortic valve stenosis show a decrease in both LVMI and LVMI/LVEDVI and an
      improvement in diastolic filling, whereas in patients with aortic regurgitation,
      LVMI decreases less rapidly than LVEDVI, causing concentric remodeling of the LV,
      most likely explaining the observed deterioration of diastolic filling in these
      patients.

PMID- 12505233
TI  - Association between increased iron stores and impaired endothelial function in
      patients with hereditary hemochromatosis.
AB  - OBJECTIVES: We studied associations between iron status and early functional and
      structural vascular abnormalities in patients with hereditary hemochromatosis
      (HH). BACKGROUND: Iron may be involved in atherogenesis, and patients bearing a
      genetic mutation associated with HH are possibly at risk of developing coronary
      heart disease. METHODS: We studied the vascular properties of 41 HH patients who
      had homozygosity for the C282Y mutation, along with 51 age-matched control
      subjects, by determination of endothelium-dependent dilation (EDD) of the
      brachial artery and intima-media thickness (IMT) of the carotid artery. RESULTS:
      Male HH patients who were not receiving phlebotomy therapy showed a reduced EDD
      and increased IMT compared with controls and HH patients receiving therapy. In
      female HH patients, irrespective of treatment status, vascular parameters were
      not different from those of controls, and none of these patients had severe iron
      overload. In HH patients, increased iron load was significantly associated with
      reduced EDD and increased IMT. Moreover, we found a positive correlation between
      body iron stores and indicators of oxidative stress. When previously untreated
      male HH patients were re-investigated after intensive phlebotomy therapy, a
      significant improvement in EDD was observed (2.6 +/- 1.3% before vs. 5.5 +/- 2.1%
      after treatment, p = 0.0015). CONCLUSIONS: Impaired endothelial function and
      increased IMT are associated with iron overload, with subsequent induction of
      oxidative stress, and are not linked to a genetic disability in HH patients.
      Consequent iron-depletion therapy normalizes endothelial function and may thus
      reduce the increased risk of cardiovascular events. Female patients may be at a
      reduced risk, presumably due to continuous iron loss by menstruation.

PMID- 12505234
TI  - Assessment of peripheral artery tonometry in the detection of treadmill exercise
      induced myocardial ischemia.
AB  - OBJECTIVES: We sought to assess the added diagnostic value of peripheral artery
      tonometric (PAT) measurements, based on finger pulsatile arterial volume changes,
      to standard 12-lead stress electrocardiography (ECG), for detecting exercise
      induced myocardial ischemia, using single-photon emission computed tomography
      (SPECT) as the standard of comparison in a double-blinded, multicenter protocol.
      METHODS: An automated algorithm for identifying myocardial ischemia from PAT was
      derived from 345 training cases. The PAT outcome was combined with the ECG result
      (ischemic, nonischemic, or equivocal), giving a PAT-enhanced value. A threshold
      of normality was determined to optimize agreement with the SPECT results in the
      training sample. The PAT-enhanced analysis was then validated in 616 subjects,
      only two of whom had technically unacceptable PAT studies. RESULTS: In the
      validation cohort, receiver operating characteristic curve analysis of the PAT
      enhanced diagnosis yielded an area under the curve of 0.72, a sensitivity of
      63.5%, compared with 44.7% for ECG alone (p < 0.0001), and a specificity of 67.8%
      common to both ECG and PAT-enhanced diagnoses. Similar results were found in the
      training sample. Although over 10% of validation subjects had equivocal ECG
      results, with the aid of PAT, it was possible to provide diagnostic information
      for all but one subject. CONCLUSIONS: Peripheral artery tonometry may be useful
      for improving the diagnosis of exercise-induced myocardial ischemia by both
      enhancing the sensitivity without impairing the specificity and increasing the
      percentage of definitive test results.

PMID- 12505235
TI  - If only cardiologists did properly measure blood pressure. Blood pressure
      recordings in daily practice and clinical trials.
AB  - Blood pressure (BP) is often measured sloppily, not only in clinical practice,
      where seemingly more important cardiovascular information, such as ejection
      fraction, cardiac output, and wedge pressure, is available, but also in clinical
      trials. Yet, definite conclusions often hinge on accurate BP measurements. In the
      Heart Outcomes Prevention Evaluation (HOPE) study, the conclusion of the benefits
      being relatively independent of BP was challenged by 24-h ambulatory BP
      monitoring in a subgroup that documented a larger fall in BP than reported in the
      whole population. Whether measured in office or clinical trials, BP is an
      important clinical tool that should be treasured by practitioners and clinical
      investigators alike.

PMID- 12505236
TI  - Anemia and poor prognosis in advanced heart failure.

PMID- 12505238
TI  - Use of term "non-Q infarction" is questioned.

PMID- 12505240
TI  - Statistical challenges in the evaluation of surrogate endpoints in randomized
      trials.
AB  - The validation of surrogate endpoints has been studied by Prentice, who presented
      a definition as well as a set of criteria that are equivalent if the surrogate
      and true endpoints are binary. Freedman et al. supplemented these criteria with
      the so-called proportion explained. Buyse and Molenberghs proposed to replace the
      proportion explained by two quantities: (1). the relative effect, linking the
      effect of treatment on both endpoints, and (2). the adjusted association, an
      individual-level measure of agreement between both endpoints. In a multiunit
      setting, these quantities can be generalized to a trial-level measure of
      surrogacy and an individual-level measure of surrogacy. In this paper, we argue
      that such a multiunit approach should be adopted because it overcomes
      difficulties that necessarily surround validation efforts based on a single
      trial. These difficulties are highlighted.

PMID- 12505241
TI  - Surrogate markers and joint models for longitudinal and survival data.
AB  - There is increasing interest in the use of surrogate marker endpoints in
      comparative clinical trials to make decisions about treatment efficacy. They are
      attractive because a trial using a surrogate endpoint is typically smaller,
      faster, and cheaper than a trial using a clinical endpoint. In seminal work,
      Prentice gave a framework for studying surrogate endpoints and a formal
      definition of conditions that a marker should satisfy to be a valid surrogate
      endpoint. These definitions involve consideration of the joint distribution of
      the marker and the clinical endpoint. It is well recognized that the formal
      definition is unlikely to be satisfied in practice, and thus quantifying the
      proportion of treatment explained (PTE) by a surrogate marker is an intuitively
      appealing concept. Freedman et al. suggested a statistic to quantify the PTE. In
      the situation of a censored clinical event time and a longitudinal marker,
      calculation of this statistic requires fitting two different survival models. We
      show that for these two models to be consistent with one another requires a
      specific assumption about the joint model for the longitudinally measured marker
      and the clinical endpoint. Furthermore, in a simulation study we show that the
      Freedman et al. PTE statistic and other measures of surrogacy, motivated by the
      Prentice framework, can be estimated using the joint model. Thus to evaluate a
      marker as a potential surrogate endpoint it is crucial to understand the joint
      distribution of the marker and the clinical endpoint.

PMID- 12505242
TI  - Design and analysis of two-period studies of potentially disease-modifying
      treatments.
AB  - A number of two-period designs have been introduced in the neurological clinical
      trials literature to evaluate the effects of treatment on progressive diseases,
      using names such as withdrawal, active-extension, randomized withdrawal,
      randomized start, and staggered-start designs. After parallel groups complete the
      first period, treatment is either initiated or withdrawn in the second period in
      a subset of subjects. The purpose of the second period is to provide evidence of
      whether any effect of treatment observed during the first period is long-term
      ("disease-modifying") or short-term and transitory ("symptomatic"). A four-arm
      version, which we term a complete two-period design, has active/active,
      active/placebo, placebo/active and placebo/placebo respective treatment
      assignments in the two periods. We provide statistical models for these designs,
      describe some of the appropriate analyses, and investigate the relative
      efficiencies of various allocations and special cases. We describe extensions to
      full and partial factorial versions of such designs which permit efficient and
      simultaneous evaluation of disease-modifying and symptomatic effects of two or
      more treatments, along with possible interactions. Advantages and limitations of
      the various designs are discussed.

PMID- 12505243
TI  - Sample size correction for treatment crossovers in randomized clinical trials
      with a survival endpoint.
AB  - Sample size determination in randomized clinical trials usually relies on the
      determination of survival rates at the time of analysis in both groups, under the
      null and the alternative hypotheses, the type I and II error rates and on other
      assumptions, such as proportional hazards in most cases. However, in numerous
      clinical trials for malignant chronic diseases, it is currently common that a
      patient allocated to the conventional treatment group would receive the
      experimental treatment in case of disease progression or relapse. Such crossovers
      are usually not taken into account when computing the sample size of the trial,
      but generally result in a decreased power of the trial. In this work, we aimed to
      correct the sample size of such trials to control the power, under an exponential
      survival assumption.

PMID- 12505244
TI  - The method of minimization for allocation to clinical trials. a review.
AB  - Minimization is a largely nonrandom method of treatment allocation for clinical
      trials. We conducted a systematic literature search to determine its advantages
      and disadvantages compared with other allocation methods. Minimization was
      originally proposed by Taves and by Pocock and Simon. The latter paper introduces
      a family of allocation methods of which Taves' method is the simplest example.
      Minimization aims to ensure treatment arms are balanced with respect to
      predefined patient factors as well as for the number of patients in each group.
      Further extensions of the method have also been proposed by other authors.
      Simulation studies show that minimization provides better balanced treatment
      groups when compared with restricted or unrestricted randomization and that it
      can incorporate more prognostic factors than stratified randomization methods
      such as permuted blocks within strata. Some more computationally complex methods
      may give an even better performance. Concerns over the use of minimization have
      centered on the fact that treatment assignments may be predicted with certainty
      in some situations and on the implications for the analysis methods used. It has
      been suggested that adjustment should always be made for minimization factors
      when analyzing trials where minimization is the allocation method used. The use
      of minimization may sometimes result in added organizational complexity compared
      with other methods. Minimization has been recommended by many commentators for
      use in clinical trials. Despite this it is still rarely used in practice. From
      the evidence presented in this review, we believe minimization to be a highly
      effective allocation method and recommend its wider adoption in the conduct of
      randomized controlled trials.

PMID- 12505245
TI  - Biomarker-based methods for determining noncompliance in a prevention trial.
AB  - The Prostate Cancer Prevention Trial (PCPT) is a 7-year randomized trial of 18000
      men designed to test a daily dose of finasteride (5 mg/d) for the primary
      prevention of prostate cancer. Compliance is assessed every 6 months by
      determining the percentage of pills consumed since the previous visit. In
      addition, levels of 5 alpha-dihydrotestosterone (DHT) are measured at yearly
      intervals in a random subset of 5% of participants in the trial as part of a
      substudy to investigate the potential of this biomarker for monitoring
      compliance. Motivated by this substudy, we outline three biomarker-based rules
      for monitoring compliance over time in prevention trials. We make comparisons
      among the rules using receiver operating characteristic curves. We illustrate the
      methods using the biomarker DHT in the PCPT substudy with pill counts as a gold
      standard, and in a simulation study under a hypothetical true gold standard. Our
      results indicate that simple absolute threshold monitoring rules perform just as
      well as more complicated rules that utilize the entire biomarker history.

PMID- 12505246
TI  - Comparison of baseline characteristics and mortality experience of participants
      and nonparticipants in a randomized clinical trial: the Physicians' Health Study.
AB  - Although subjects randomized into clinical trials tend to have different
      mortality experiences from those not randomized, few studies have examined how
      baseline characteristics may explain these differences. We used the recruitment
      experience of the Physicians' Health Study (PHS) to describe and compare
      subgroups of subjects ultimately randomized - or not - into the PHS. A total of
      112528 male physicians ages 40-84 years responded to letters of invitation and
      baseline questionnaires sent to 261248 subjects. Baseline information was
      collected on eligibility criteria, plus lifestyle and clinical risk factors.
      Total, cardiovascular, cancer, and other mortality were determined through the
      National Death Index after a mean follow-up of 5.39 years. Respondents had 19 and
      19% lower total and cardiovascular mortality rates than nonrespondents.
      Similarly, willing respondents were 19 and 16% less likely to die than unwilling
      respondents. However, much of this difference in mortality was explained by
      disease and lifestyle factors. Respondents who were eligible for the PHS had
      significantly lower age-adjusted relative risks (RRs) that were attenuated but
      remained substantially below 1 upon multivariate adjustment in models for total
      (RRs from 0.48 to 0.79), cardiovascular (from 0.40 to 0.85), and cancer mortality
      (from 0.55 to 0.87). Finally, a nearly halving in the age-adjusted risk of total
      and cause-specific mortality among men completing a run-in and randomized into
      PHS compared with those not randomized was nominally altered upon adding all
      covariates into multivariate models. In conclusion, a difference in mortality
      rates according to willingness to participate in a trial was explained by disease
      and lifestyle factors. In contrast, diseases and risk factors explain some, but
      not all, of the lower mortality rates of physicians based on eligibility status
      and their ability to complete a run-in phase.

PMID- 12505247
TI  - Evaluating surrogate endpoints.

PMID- 12505248
TI  - Women's angiographic vitamin and estrogen trial: design and methods.
AB  - The Women's Angiographic Vitamin and Estrogen trial was a randomized, double
      blind, placebo-controlled study designed to test the efficacy of estrogen
      replacement and antioxidant vitamins for preventing angiographic progression of
      coronary artery disease. Postmenopausal women with one or more angiographically
      documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2
      factorial randomization to active hormone replacement therapy (conjugated
      estrogens for women who had had a hysterectomy or conjugated estrogens with
      medroxyprogesterone for women with intact uteri) or placebo and to active
      vitamins E and C or their placebos. Seven clinical centers, five in the United
      States and two in Canada, randomized 423 women between July 1997 and July 1999.
      Quantitative coronary angiography was performed at baseline and repeated after
      projected mean follow-up of 3 years.

PMID- 12505249
TI  - A randomized trial of the effect of a plant-based dietary pattern on additional
      breast cancer events and survival: the Women's Healthy Eating and Living (WHEL)
      Study.
AB  - The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized
      controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at
      markedly raising circulating carotenoid concentrations from food sources, in
      reducing additional breast cancer events and early death in women with early
      stage invasive breast cancer (within 4 years of diagnosis). The study randomly
      assigned 3088 such women to an intensive diet intervention or to a comparison
      group between 1995 and 2000 and is expected to follow them through 2006. Two
      thirds of these women were under 55 years of age at randomization. This research
      study has a coordinating center and seven clinical sites. Randomization was
      stratified by age, stage of tumor and clinical site. A comprehensive intervention
      program that includes intensive telephone counseling, cooking classes and print
      materials helps shift the dietary pattern of women in the intervention. Through
      an innovative telephone counseling program, dietary counselors encourage women in
      the intervention group to meet the following daily behavioral targets: five
      vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of
      fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12,
      24 or 36, 48 and 72 months. These assessments can include dietary intake
      (repeated 24-hour dietary recalls and food frequency questionnaire), circulating
      carotenoid concentrations, physical measures and questionnaires about health
      symptoms, quality of life, personal habits and lifestyle patterns. Outcome
      assessments are completed by telephone interview every 6 months with medical
      record verification. We will assess evidence of effectiveness by the length of
      the breast cancer event-free interval, as well as by overall survival separately
      in all the women in the study as well as specifically in women under and over the
      age of 55 years.

PMID- 12505250
TI  - Measuring the cost-effectiveness of lipid-lowering drugs in the elderly: the
      outcomes research and economic analysis components of the PROSPER trial.
AB  - Little information exists to quantify the functional status and economic
      consequences of lipid-lowering therapy in elderly patients. We describe the
      design of the cost-effectiveness component of the first large, randomized,
      placebo-controlled trial of lipid-lowering therapy in subjects aged 70 years or
      older. The PROspective Study of Pravastatin in the Elderly at Risk has randomized
      5804 men and women 70-82 years old, with existing vascular disease or related
      risk factors, to receive 40 mg/d of pravastatin or placebo. The cost
      effectiveness study will be based on within-trial observations of differences
      between the two study arms in rates of myocardial infarction, stroke and related
      vascular disease outcomes (including vascular dementia). In addition to comparing
      within-trial clinical outcomes, we will model the projected changes in life
      expectancy and cardiovascular outcome rates that would be seen with lifelong use
      of the drug, based on the risk reduction rates seen in the trial as well as
      baseline observational data from the three countries where the trial is being
      conducted (Scotland, Ireland and the Netherlands). A state transition (Markov)
      model will be constructed to estimate the likely states of health, functional
      status and health care resource utilization (including lipid-lowering drug costs)
      in a cohort of elderly patients with versus without pravastatin therapy over a
      series of 1-year cycles until death. In addition, a standard measure of utility
      (the Health Utilities Index) will be administered to all study subjects to permit
      calculation of quality-adjusted life-years gained with this regimen. This
      approach will make it possible to go beyond the calculation of a single endpoint
      for each subject, and to translate the trial findings into definitions of
      effectiveness and outcomes that will be relevant to the ongoing debate concerning
      how best to relate the benefits of such medications to their costs.

PMID- 12505251
TI  - Molecular cytogenetic aberrations in CD30+ anaplastic large cell lymphoma cell
      lines.
AB  - Anaplastic large cell lymphomas (ALCL) in children represent a heterogeneous
      group of neoplasms with regard to the cell lineages involved. The chromosomal
      5q35 breakpoint (bp) and the expression of the NPM/ALK fusion gene are the most
      remarkable molecular cytogenetic features of these malignancies. To identify new
      locations of ALCL-related oncogenes, comparative genomic hybridization (CGH) was
      applied to three ALCL cell lines (SU-DHL-1, Karpas 299, and DEL) exhibiting the
      5q35 bp and expressing the NPM/ALK transcript. The CGH profiles were compared
      with those obtained with DNA from U937, HL-60 cells, and altered lymph nodes from
      two children with ALCL. Significant DNA copy number gains and/or losses were
      observed on several chromosomes in all ALCL cell lines. Distinct amplicons were
      detected on 1q21 approximately q44 (DEL), 7q12 (SU-DHL-1), and 1q12 approximately
      q22 (Karpas 299) regions. The NPM/ALK fusion gene was confirmed by fluorescence
      in situ hybridization (FISH) analysis in more than 80% of interphase nuclei and
      metaphase spreads. Enhanced expression of TGF-beta2 and c-MET candidate genes
      located at the amplified regions was revealed in DEL and SU-DHL1 cell lines by
      Northern blot analysis. These findings delineate chromosomal imbalances in ALCL
      derived cell lines in parallel with high level of amplification covering target
      DNA sequences, which could play a role in ALCL pathogenesis.

PMID- 12505252
TI  - Recurring breakpoints of 1p13 approximately p22 in osteochondroma.
AB  - Cytogenetic studies of osteochondromas are scarce but have previously shown
      recurring clonal aberrations involving chromosome 8. We have studied a series of
      eight tumors and have found recurring aberrations not only involving chromosome
      8, but also chromosome 1 in five of the seven abnormal tumors. Surprisingly,
      three of the chromosome 1 aberrations involved pericentric inversions. Four
      tumors showed aberrations involving the region 1p13 approximately p22 by
      mechanisms including inversion, insertion, and translocation. These findings
      indicate that aberrations of chromosome 1p, in a region spanning 1p13
      approximately p22, may be nonrandomly involved in the cytogenetic progression of
      osteochondroma.

PMID- 12505253
TI  - Complex cytogenetic abnormalities including telomeric associations and MEN1
      mutation in a pediatric ependymoma.
AB  - Ependymomas are neuroectodermal tumors of the brain and spinal cord. Some
      recurrent cytogenetic aberrations have been reported in these tumors, including
      alterations involving chromosomes 22, 6, and 11. However, consistent molecular
      alterations have not been identified in ependymal tumors. We studied a recurrent
      ependymoma in a 3-year-old patient by standard cytogenetic and molecular analysis
      of TP53 and MEN1 genes. In the present case, we found many of the cytogenetic
      features previously described as being recurrent in ependymomas, including
      unstable telomeric alterations. Furthermore, we detected a novel acquired
      heterozygous mutation in the MEN1 gene. The chromosomal instability produced by
      the telomeric alterations and the mutation in the MEN1 gene could be important
      events in the tumorigenesis of ependymomas.

PMID- 12505254
TI  - Characterization of chromosomal aberrations in a case of glioblastoma multiforme
      combining cytogenetic and molecular cytogenetic techniques.
AB  - A case of glioblastoma multiforme (GBM) that was investigated with a broad
      spectrum of cytogenetic and molecular cytogenetic techniques is reported. The
      results of cytogenetic studies, interphase fluorescence in situ hybridization,
      comparative genomic hybridization, and spectral karyotyping (SKY) are reported.
      Various structural chromosomal aberrations were identified, among which
      aberrations involving chromosome arm 2p were especially frequent. Using SKY, six
      translocations not previously described in GBM are reported.

PMID- 12505255
TI  - Trisomy 15 in a case of pediatric hemangiopericytoma and review of the
      literature.
AB  - This study reports on a pediatric case of hemangiopericytoma (HPC) showing
      trisomy 15 as a sole anomaly. Trisomy 15 was observed in a total of 11 cells
      harvested at a very early passage from two different in-situ cultures. Trisomy
      15, as a sole anomaly, has been described in hematologic disorders such as
      myelodysplastic syndromes but, to our knowledge, has never been documented in
      solid tumors. This is the first report of HPC with trisomy 15.

PMID- 12505256
TI  - Analysis of BRCA1, TP53, and TSG101 germline mutations in German breast and/or
      ovarian cancer families.
AB  - About 5%-10% of breast cancers are considered to be hereditary and associated
      with germline mutations of specific genes. As yet, the most frequently affected
      genes identified are BRCA1 and BRCA2, but also other genes such as TP53 are
      supposed to influence the predisposition toward breast cancer. In the present
      study, we analyzed patients of 19 German families with early onset breast cancer
      and/or a family history of breast and/or ovarian cancer for the presence of
      mutations in BRCA1 and TP53. In addition, we screened for germline mutations in
      the putative tumor suppressor gene TSG101. For this purpose we used direct
      sequence analysis of the entire coding regions for all three genes and, in the
      case of BRCA1, single-strand conformation polymorphism analysis and protein
      transcription-translation assays. We identified eight previously described
      polymorphisms and several aberrations in BRCA1: 1 unclassified missense mutation,
      3 small protein truncating mutations, 1 novel pseudoexon, and 5 splicing
      variants. No mutation was detected in TP53. Analysis of TSG101 transcripts
      revealed an aberrant transcript in two breast cancer patients belonging to the
      same family, suggesting TSG101 as a predisposing gene in hereditary breast
      cancer.

PMID- 12505257
TI  - SKY detection of chromosome rearrangements in two cases of tMDS with a complex
      karyotype.
AB  - In this study, we used spectral karyotyping (SKY) and fluorescence in situ
      hybridization (FISH) as complementary techniques for the analysis of two therapy
      related secondary myelodysplastic syndrome (t-MDS) cases with complex karyotypes,
      previously analyzed by G-banding. Different types of SKY's cytogenetic
      contributions include confirmation of G-banding results, identification of
      partially characterized rearrangements, identification of marker chromosomes
      unidentified by G-banding, and detection of cryptic reciprocal translocations. In
      particular, the ability of SKY to clarify a number of markers led to the
      comprehension of clonal evolution. The common aberration found in these two t-MDS
      cases was the fragility of chromosome 5 and monosomy of chromosome 18. We clearly
      present that the use of SKY combined with conventional G-banding analysis and
      FISH has assisted in the identification of important chromosomal events that may
      play a key role in the development of t-MDS.

PMID- 12505258
TI  - Involvement of 1p36 region in two cases of adenocarcinoma of the ampulla of
      Vater.
AB  - Cancer of the ampulla of Vater is an uncommon disease that leads to death in 60%
      of affected patients. There is general agreement that local spread of the tumour
      (T stage) is the only significant and independent prognostic factor for this
      cancer. Although the genetic mechanisms underlying the development of ampullary
      tumors are still mostly unknown because of their rarity, the genetic anomalies
      involved in tumor development might serve as additional prognostic markers.
      Cytogenetic studies may be helpful in identifying specific chromosome regions
      involved in these cancers. We studied two cases of poorly differentiated
      ampullary adenocarcinomas using conventional and molecular cytogenetics on direct
      preparations. The cytogenetic analysis revealed complex chromosome complements in
      both cases with different cell lines, rearrangements, chromosome markers, and
      aneuploidies. Interestingly, the involvement of the 1p36 region was a feature of
      both cases. The molecular studies showed an absence of high microsatellite
      instability (MSI) and the morphologic and immunohistochemical pattern did not
      suggest MSI. This study may help to characterized ampullary adenocarcinomas
      showing complex karyotypes, poor differentiation and poor prognosis. In these
      tumors, the 1p36 region may play a relevant role in the progression towards a
      high grade of anaplasia.

PMID- 12505259
TI  - Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL
      gene rearrangement: case report and review of the literature.
AB  - Chronic myelocytic leukemia (CML) is a chronic myeloproliferative disorder
      characterized by cytogenetic or molecular evidence of Philadelphia (Ph)
      chromosome, t(9;22)(q34;q11). Mild to moderate eosinophilia is commonly seen in
      CML. However, eosinophilia as a dominant feature of CML is extremely rare. We
      describe a case of Ph(-) CML with eosinophilia. Loeffler endocarditis, and
      t(9;12)(q34;p13) that resulted in an ETV6-ABL gene rearrangement/fusion
      identified to the best of our knowledge, for the first time by using commercially
      available fluorescence in situ hybridization probes.

PMID- 12505260
TI  - Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory
      secondary acute promyelocytic leukemia: a case report and review of the
      literature.
AB  - A 69-year-old woman developed microgranular acute promyelocytic leukemia (APL-M3)
      10 months after receiving adjuvant cyclophosphamide, doxorubicin, and paclitaxel
      for breast cancer. Replicate bone marrow aspirate karyotypes contained a
      translocation between the long arms of chromosomes 15 and 17, but not at
      breakpoints typical for APL. Fluorescence in situ hybridization paints and
      RARalpha/PML cosmid probes verified that the breakpoints on chromosomes 15 and 17
      were proximal to both the PML and RARalpha genes; t(15;17)(q13;12). Although the
      patient received induction chemotherapy and a several month trial of all-trans
      retinoic acid (ATRA), there was no clinical improvement or hematological
      remission. We suspect that this patient developed postchemotherapy secondary APL
      with an atypical t(15;17), which rendered her leukemic cells unresponsive to ATRA
      therapy.

PMID- 12505261
TI  - Identification of t(15;17) and a segmental duplication of chromosome 11q23 in a
      patient with acute myeloblastic leukemia M2.
AB  - A 32-year-old man was newly diagnosed with acute myelocytic leukemia, classified
      as acute myeloblastic leukemia with maturation (AML-M2) according to the French
      American-British classification system. Conventional chromosome analysis before
      chemotherapy treatment revealed an abnormal karyotype: a possible segmental
      duplication of 11q23, plus a translocation between chromosomes 15 and 17
      [t(15;17) (q22;q21.1)] in the majority of cells analyzed. Fluorescence in situ
      hybridization analysis using commercially available probes confirmed the
      cytogenetic findings. To our knowledge, this is the first report of a combination
      of t(15;17) and a segmental duplication of 11q23 in a patient with AML-M2.

PMID- 12505262
TI  - Cryptic t(X;18), ins(6;18), and SYT-SSX2 gene fusion in a case of intraneural
      monophasic synovial sarcoma.
AB  - A 54-year-old male presented with a spontaneous peroneal nerve palsy and a
      diagnosis of monophasic synovial sarcoma (SS) was rendered by histologic
      examination. Cytogenetic analysis revealed a complex abnormal karyotype without
      evidence of the typical t(X;18)(p11;q11) associated with SS. Subsequent reverse
      transcriptase polymerase chain reaction analysis showed the presence of an
      SYT/SSX2 fusion transcript, confirming the presence of a cyptic t(X;18). In light
      of -X, -18 and marker chromosomes evident in the G-band karyotype, it was
      suspected that a cryptic chromosomal rearrangement involving the marker
      chromosomes would harbor an X;18 fusion. Multi-colored karytotyping (M-FISH)
      revealed a previously unrecognized t(X;18) and t(5;19) in the marker chromosomes
      as well as unrecognized ins(6;18) and t(16;20). The addition of M-FISH analysis
      in this case led to the identification of complex inter-chromosomal
      rearrangements, thus providing an accurate karyotype.

PMID- 12505263
TI  - Frequency of 657del(5) mutation of the NBS1 gene in the Czech population by
      polymerase chain reaction with sequence specific primers.
AB  - Nijmegen breakage syndrome is an autosomal recessive chromosomal instability
      syndrome characterized by microcephaly, immunodeficiency, radiosensitivity, and
      predisposition to lymphoid malignancy. A truncating deletion [657del(5)] in exon
      6 of the nibrin NBS1 gene is the most frequent cause of the syndrome. Slavic
      populations carry this mutation in a high frequency. Here, we present polymerase
      chain reaction with sequence specific primers as a method for the detection of
      Slavic NBS1 mutation and confirm the high carrier frequency in the Czech
      population (combined frequency from both studies: 1/106, 95% CI = 1/331 to 1/46).

PMID- 12505264
TI  - Expression of the HMGA2-LPP fusion transcript in only 1 of 61 karyotypically
      normal pulmonary chondroid hamartomas.
AB  - The HMGA2 gene has been found to be rearranged in a variety of benign solid
      tumors. However, in all tumor entities where aberrations of the corresponding
      chromosomal region have been found, a large percentage of tumors do not show any
      detectable cytogenetic deviation. Thus, the question arises whether or not in
      some of these cases, small subpopulations of tumor cells characterized by HMGA2
      rearrangements exist. The existence of these populations would strongly suggest a
      secondary nature of the chromosomal aberrations. Herein, we have addressed this
      question by RT-PCR analyses of the HMGA2-LPP fusion resulting from t(3;12)(q27
      approximately q28;q14 approximately q15) in a series of 61 pulmonary chondroid
      hamartomas (PCH) with an apparently normal karyotype. As a result, the HMGA2-LPP
      fusion transcript was amplified in only one of 61 PCH with a normal karyotype. In
      this case, fluorescence in situ hybridization analysis revealed a hidden
      chromosomal aberration. The absence of the HMGA2-LPP fusion in small populations
      of tumors with a normal karyotype suggests the primary nature of chromosomal
      rearrangements in the development of PCH affected by those aberrations.

PMID- 12505265
TI  - Trisomy 21 as the only recurrent chromosomal anomaly in a clinically aggressive
      ovarian carcinoma.
AB  - A case of a highly aggressive grade III poorly differentiated serous
      adenocarcinoma of the ovary was determined to exhibit trisomy 21 as the sole
      chromosomal abnormality. To eliminate the possibility that this trisomy was
      constitutional, the patient's blood cells were subjected to locus specific
      21q22.13 approximately q22.2 chromosome probe using fluorescence in situ
      hybridization (FISH). Concurrently, using FISH and the same probe the tumor
      tissue was also tested. We discovered that 48% of the cells of the tumor tissue
      either had trisomy or tetrasomy of chromosome 21. Two normal signal patterns for
      chromosome 21 in blood and absence of Down morphology in the patient confirmed
      the presence of trisomy to be limited to the tumor tissue. To the best of our
      knowledge, this is the only case where trisomy 21 was shown to be the sole
      chromosomal anomaly in a serous carcinoma of the ovary. Tumorigenesis in
      gynecologic malignancies is discussed in the light of oncogenes present on
      chromosome 21.

PMID- 12505266
TI  - Cryptic translocation of PML/RARA on 17q. A rare event in acute promyelocytic
      leukemia.
AB  - Cryptic translocations in acute promyelocytic leukemia are rare. Usually the gene
      fusion PML/RARA is located on chromosome 15. Combined cytogenetic, fluorescence
      in situ hybridization (FISH), and molecular (polymerase chain reaction [PCR])
      analysis were employed for the diagnosis and precise localization of the fusion
      gene. Conventional cytogenetics showed a normal karyotype; PCR showed a typical
      PML/RARA rearrangement in exon 1. FISH analysis revealed that a submicroscopic
      part of chromosome 15 had been inserted into 17q. This case adds further
      information on alternative ways of rearrangement of the PML/RARA genes, possibly
      correlated with all-trans retinoic acid resistance.

PMID- 12505267
TI  - Sensitivity of detection of B-cell lymphoma in bone marrow by fluorescence in
      situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) was used in a retrospective study of
      bone marrow aspirate specimens submitted for conventional cytogenetic analysis
      with an indication of B-cell lymphoma. About 50% of cytogenetically normal
      samples, which had been identified as containing lymphoma by pathology, showed
      small cell populations with an IGH gene rearrangement by FISH. This study
      demonstrates that FISH scoring of 750 nuclei provides a 99% chance of identifying
      the presence of lymphoma with a 14q32 aberration when this population constitutes
      approximately 8% of the bone marrow.

PMID- 12505268
TI  - A corrected karyotype for the SH-SY5Y human neuroblastoma cell line.

PMID- 12505269
TI  - Role of metabolism by flavin-containing monooxygenase in thioacetamide-induced
      immunosuppression.
AB  - Thioacetamide has been known to cause immune suppression. The object of the
      present study is to investigate the role of metabolic activation by flavin
      containing monooxygenases (FMO) in thioacetamide-induced immune response. To
      determine whether the metabolites of thioacetamide produced by FMO causes the
      immunosuppression, methimazole, an FMO inhibitor, was used to block the FMO
      pathway. Antibody-forming cell (AFC) response measured in BALB/c mice sensitized
      with sheep red blood cells (SRBCs) was compared between the groups treated with
      thioacetamide in the presence or absence of methimazole pretreatment. The
      pretreatment abolished the decrease in AFC number observed in the mice treated
      with thioacetamide alone. In addition, when spleen cells isolated from untreated
      mice were exposed to thioacetamide with a drug-metabolizing system, liver
      microsome and NADPH, for 4 h in vitro prior to the stimulation with mitogens,
      such as lipopolysaccharide (LPS) or concanavalin A (Con A), spleen cell
      proliferation was also decreased. The inhibitory effect of thioacetamide on cell
      growth was not detectable without the liver microsome. Moreover, the
      thioacetamide-suppressed proliferation of spleen cells in the presence of the
      metabolic activation system was prevented when coincubated with either SKF-525A,
      a cytochrome P450 (P450) inhibitor, or methimazole. We also found that the level
      of interleukin-2 (IL-2) in the culture supernatant was decreased by thioacetamide
      treatment and that the decrease of IL-2 level can be prevented by either SKF-525A
      or methimazole coincubation. Since IL-2 is one of the responsible factors that
      determine the proliferation level of lymphocytes, the change of IL-2 production
      was consistent with that of lymphoproliferation. In conclusion, thioacetamide
      induced immunosuppression was, at least in part, due to the metabolites produced
      by FMO as well as by P450.

PMID- 12505270
TI  - Short term feeding of hexadienal to postnatal rats: effects on stomach aldehyde
      dehydrogenase.
AB  - Since a number of food and food products contain 2,4-hexadienal (HX), an
      unsaturated aldehyde, human exposure to HX is likely. Long term HX feeding to
      rodents induces forestomach cancers. Aldehyde dehydrogenases (ALDH) are key
      enzymes in the stomach for the metabolism of aldehydes. We examined the effect of
      short term feeding of HX on ALDH activity using HX as the substrate (HXDH) in
      different tissues of the GI tract. Feeding HX at a dose of 200 mg/kg body
      weight/day to post-suckling rats for 5 days elevated HXDH activity in the
      forestomach and esophagus but not in the glandular stomach, liver, small
      intestine or kidney. The induction of HXDH by HX was evident at 12.5 mg/kg dose
      and showed a dose-dependence up to 200 mg/kg. Increase in HXDH was time dependent
      but detectable after the first feeding (1 day). A similar dose (200 mg/kg) of
      acetylaldehyde or ethanol had no effect on HXDH activity. The increase in HXDH
      level in the forestomach and esophagus was transient. HXDH activity returned to
      normal 4 days after withdrawal of HX. Zymograms of gastric HXDH isozyme patterns
      in control and HX-fed counterparts were similar but showed selective increase in
      two particular forms in the forestomach. It is possible that these isoforms
      metabolize HX differently resulting in an accumulation of potential carcinogenic
      metabolites within the forestomach.

PMID- 12505271
TI  - Assessment of bone metabolism in cadmium-induced renal tubular dysfunction by
      measurements of biochemical markers.
AB  - Bone metabolism related to the severity of cadmium (Cd)-induced renal tubular
      dysfunction (RTD) was assessed by measuring several bone biochemical markers.
      Fifty-three female subjects with RTD aged 65-76 years (mean 70.0+/-3.3 years) and
      who lived in the Cd-polluted Jinzu River basin in Toyama, Japan were studied.
      Bone alkaline phosphatase (bone-ALP), intact bone Gla-protein (intact-BGP) and
      carboxy-terminal propeptide of type I collagen (PICP) in serum as bone formation
      markers and pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in urine as bone
      resorption markers were measured. All markers of bone turnover were increased and
      significantly correlated with each other, suggesting that bone formation and
      resorption were coupled and increased in Cd-induced RTD. Fractional excretion of
      beta(2)-microglobulin (beta(2)-m, FE(beta 2-m)) as an index of severity of Cd
      induced RTD was extremely varied ranging from 0.45 to 53%. There were no
      significant correlations between FE(beta 2-m) and each of the five bone
      biochemical markers. The bone turnover in Cd-induced RTD appeared to be
      determined by the glomerular filtration rate (GFR): in subjects with GFRs above
      50 ml/min, the levels of bone-ALP or intact-BGP tended to be inversely related to
      the GFRs, whereas in subjects with GFRs below 40 ml/min, those levels tended to
      decrease. These results suggest that the bone turnover, in particular the bone
      formation, was influenced by renal tubular function as assessed by the levels of
      GFR in Cd-induced RTD.

PMID- 12505272
TI  - Zinc-metallothionein protects from DNA damage induced by radiation better than
      glutathione and copper- or cadmium-metallothioneins.
AB  - Protection of radiation-induced DNA damage by metallothionein (MT) has been
      documented, but there is no detailed information about its efficiency compared to
      other antioxidants or the effect of metals which bind to MT on the protective
      effect of MT in radiation-induced DNA damage. In this study, we used a cell-free
      system to investigate the effect of MT with other antioxidants, such as albumin
      and glutathione and we compared the efficiency of MT bound to different metals on
      radiation-induced DNA damage. DNA damage was measured by loss in ethidium
      bromide/DNA fluorescence and increased mobility of DNA on gel electrophoresis.
      Gamma rays at 30 Gy induced significant DNA damage and zinc-MT showed a
      significant higher protection from radiation-induced DNA damage than both
      glutathione and albumin. Metallothionein bound to other metals, such as copper
      and cadmium, also showed protection of radiation-induced DNA damage, but the
      protective effect by zinc-MT was the highest. These results suggest that MT, in
      particular bound to zinc, is a high-capacity antioxidant to protect radiation
      induced DNA damage.

PMID- 12505273
TI  - Comparative metabolism of methyl isobutyl carbinol and methyl isobutyl ketone in
      male rats.
AB  - Methyl isobutyl carbinol (MIBC) is an oxygenated solvent that is metabolized to
      methylisobutyl ketone (MIBK) and then to 4-hydroxymethyl-4-methyl-2-pentanone
      (HMP). Plasma levels of MIBC, MIBK and HMP were determined up to 12 h after a
      single oral 5 mmol/kg dose of MIBC or MIBK to male rats. The major material in
      the plasma in both cases was HMP, with similar areas-under-the-curve (AUC) and
      C(max) at 9 h after dosing. MIBK plasma levels and AUC were also comparable after
      MIBK or MIBC administration. MIBC AUC was only about 6% of the total material in
      the blood after MIBC, and insignificant after MIBK administration. No other
      metabolites were detected in the plasma under the analytical conditions used. The
      extent of metabolism of MIBC to MIBK, by comparing combined AUCs for MIBK and
      HMP, was at least 73%. The limited systemic toxicity data for MIBC are consistent
      with those for MIBK, which has been well studied. The metabolic equivalency of
      MIBC with MIBK indicates that MIBC will have a low potential for toxicity similar
      to that of MIBK, and reduces the need for additional animal studies.

PMID- 12505274
TI  - Investigating the onset of autoimmunity in A.SW mice following treatment with
      'toxic oils'.
AB  - In 1981, over 20,000 people were struck with toxic oil syndrome (TOS). H-2s
      strains of mice have been shown to develop symptoms of TOS after exposure to
      toxic oil. We examined the effects of toxic oil on A.SW mice, which are
      susceptible to chemically-induced autoimmunity, but do not spontaneously develop
      autoimmune disease. Mice were treated with three types of toxic oil: CO756 (case
      oil from Spain), RSD99 (rapeseed oil with no 3-(N-phenylamino)-1-2-propanediol
      (PAP) derivatives) and RSA99 (rapeseed oil supplemented with PAP derivatives).
      Mercuric chloride treated mice were used as a positive control. After toxic oil
      treatment, there were no consistent differences in body weight or organ weight
      (liver, kidney, thymus and spleen) as a percent of body weight at any of these
      timepoints: 2.5, 5 or 10 weeks. We also found that treatment with toxic oil did
      not induce autoantibody formation or lead to increased serum levels of IgG1,
      IgG2a or IgE at these timepoints. Conversely, at all timepoints, there were
      significant increases in organ weight as a percent of body weight in the mercury
      treated mice. Additionally, mercuric chloride treated mice had elevated serum
      levels of IgG1, IgG2a and IgE and developed anti-nuclear and anti-collagen
      antibodies.

PMID- 12505275
TI  - Effect of Bisphenol A on non-specific immunodefenses against non-pathogenic
      Escherichia coli.
AB  - We examined the effect of Bisphenol A (BPA) on non-specific defense in
      experiments with a non-pathogenic bacterium, Escherichia coli K-12. Mice were
      pretreated by a subcutaneous route with BPA (5 mg/kg body weight) for 5
      consecutive days in the back and 3 days after the last treatment, injected by the
      intra-peritoneal route with E. coli K-12. BPA pretreatment caused a decrease of T
      and B cell populations in the spleen of treated mice. After the challenge with E.
      coli, the activity to eliminate bacteria from the peritoneal cavity in the early
      stage of infection (within 24 h) was diminished compared with non-treated mice.
      BPA induced the migration of excess neutrophils into the peritoneal cavity, but
      reduced their phagocytic activity against E. coli K-12. For macrophages and
      lymphocytes, BPA reduced the population in the spleen and the accumulation at
      infection foci. The production of MCP-1 was enhanced by BPA treatment, but that
      of IL-6 was suppressed after infection. These results suggest that BPA possessed
      immunotoxicity and reduced the non-specific host defense as an acute toxicity.

PMID- 12505277
TI  - Apoptosis and toxicology--what relevance?
AB  - All cells are mortal-i.e. they can be killed if a vital metabolic process is
      blocked. All cells can engage in a variety of stress responses, such as the heat
      shock response, when vital processes are slowly, or only partially, inhibited.
      These stress responses involve detection of the damage, transduction of signals,
      and activation of a response, such as production of heat shock proteins,
      proteases, or chaperones. Many cells possess mechanisms whose purpose is to kill
      the cell. Such physiological cell death mechanisms are used to remove unwanted or
      damaged cells. Among metazoans, physiological cell death is implemented by a
      family of cysteine proteases, termed caspases, that exist in a latent state even
      in healthy cells. Cells killing themselves via activation of their caspases
      typically exhibit an appearance termed 'apoptosis'. Apoptosis is not only used to
      remove cells in physiological circumstances, such as during development, but is
      also a common response to cell stress. Thus many cells will detect damage to, or
      malfunctioning of, vital metabolic processes, and generate signals that lead to
      activation of the caspases, and apoptotic death of the cell. This has led to a
      great deal of confusion, because many drugs and toxins with known biochemical
      functions have been found to induce apoptosis, and rather than this being
      interpreted as a stress response, it has often wrongly been assumed that
      apoptosis is a direct effect of the drug or toxin.

PMID- 12505278
TI  - Fundamentals of prion biology and diseases.
AB  - One of the most remarkable changes in medicine during the last 20 years of the
      20th century was the shift from the clinical-neuropathological classification of
      Creutzfeldt-Jakob disease (CJD) and related disorders as 'transmissible
      spongiform encephalopathies' to a molecular-etiologic classification as 'prion
      diseases'. We now know that these diseases are caused by abnormalities of the
      prion protein (PrP). Specifically, CJD is caused by the conversion of the normal,
      protease-sensitive PrP isoform, designated PrP(C), to a protease resistant
      isoform, designated PrP(Sc). PrP(Sc) forms into an infectious particle, named a
      'prion', that can transmit the disease. Accumulation of PrP(Sc) in the brain
      causes neurodegeneration. The main goals of this review are to summarize our
      understanding of the attributes of the PrP molecule that give it the properties
      of an infectious agent and to describe how different alterations of the PrP
      molecule cause the multiple known prion disease variants. Finally, the emergence
      of a new variant of CJD in Great Britain and to a lesser extent in Europe and its
      relationship to the emergence of a particularly virulent form of bovine
      spongiform encephalopathy will be discussed.

PMID- 12505279
TI  - Food and cancer.
AB  - Food is an important factor in determining cancer incidence in many countries and
      regions. Food components relevant to cancer development can be divided into macro
      and microcomponents. The former tends to act indirectly. The latter usually has
      a clearly defined action, for example as genotoxic agents. Food can have both
      positive (carcinogenic) and negative (preventive) effects. Total calory intake
      appears to have a strong positive influence on cancer incidence. Food typical of
      advanced nations including fat-rich food is associated with increases in breast,
      colon and prostate cancers. Vegetables rich in antioxidants and fibers tend to
      reduce cancer incidence. Carcinogenic plant alkaloids, myctoxins and other food
      contaminants frequently enter our bodies. Heat-cooking generates genotoxicants,
      including aromatic hydrocarbons (via combustion) and heterocyclic amines (HCAs)
      through reactions involving creatin(in)e, sugar and amino acids in meat. HCAs are
      relatively newcomers as food genotoxicants and can produce breast, colon and
      prostate cancers in rodents. Some epidemiological investigations positively
      correlate HCA intake and cancer incidence. HCAs can produce other toxicological
      effects including salivary gland atrophy and myocardial degeneration. Improved
      food, better life styles and developments in the functional food industry are all
      crucila to cancer prevention.

PMID- 12505280
TI  - Low level exposures to organophosphorus esters may cause neurotoxicity.
AB  - A large number of published studies support the notion that long term, low level
      (LTLL) exposure to organophosphorus (OP) esters may cause neurological and
      neurobehavioral effects. In order to differentiate these from other effects of OP
      such as the acute cholinergic episodes, intermediate syndrome and organophosphate
      induced delayed neuropathy (OPIDN), the term Chronic Organophosphate Induced
      Neuropsychiatric Disorder (COPIND) will be used purely for the ease of reference.
      The question addressed in this particular review is whether LTLL exposure to OP
      may produce neurotoxicity. The profile and the degree of overlap of the various
      components of COPIND have been addressed elsewhere and description of the
      possible mechanisms for COPIND is outside the scope of this article. COPIND can
      be classified under two headings; those produced following one or more acute
      clinical cholinergic episodes, and those produced without such preceding attacks.
      With regards to the first group, there are a total of 11 studies, all of which
      support the existence of a positive link between exposure to OP and
      neurotoxicity; six of these studies comprise descriptions of large numbers of
      cases without controls while five additional studies employ controls. Appearance
      of neurotoxicity does not seem to be related to the number or the intensity of
      acute cholinergic attacks. With regards to the second group, three types of
      studies can be identified. Firstly, there are five studies using experimental
      animals, all of which showed a positive link between OP and neurotoxicity.
      Secondly, a total of seven case studies without controls, some involving large
      numbers of patients, concluded that there is a positive link between OP and
      neurotoxicity. Thirdly, 19 studies investigated such a link using cases and
      control groups. Of these, 15 studies (about 80%) showed a positive link and only
      four failed to identify any link between OP and neurotoxicity. Annotation of all
      the 19 studies according to ideal set of criteria showed that only a few of these
      comply with the rules of excellence and all of these few showed a positive link.
      Furthermore, the only study carried out blind without the identification of
      subjects or controls, showed a positive link between OP and neurotoxicity. This
      blind study estimated the overall incidence of a form of neurotoxicity in people
      exposed to OP to be about 40 times higher than in the general population. The
      type of neurological involvement was unique and different from OP induced
      syndromes previously described. The profile of the neurological involvement was
      similar to that in COPIND whether or not preceded by acute cholinergic episodes,
      thus providing further evidence that these two neuropathies probably share a
      similar mechanism. There is a characteristic pattern of involvement of 15
      functional indices of the autonomic nervous system examined in our laboratory.
      There are, in addition, preferential anatomical sites of target organs affected,
      selective preservation of cholinergic function within the same neuropathy
      positive site, and evidence of mal-function of cardiac chemoreceptors in patients
      exposed to OP. The peripheral nerve involvement in OP exposure is predominantly
      sensory in nature affecting both small and large fibre populations.
      Neurobehavioral involvement of mainly cognitive dysfunction and other features
      are also described in other studies. The weight of current evidence is therefore
      very much in favor of the motion that chronic low-level exposure to OP produces
      neurotoxicity. Criticisms levelled against this motion are unfounded and probably
      misconceived.

PMID- 12505281
TI  - Epidemiology of hepatocellular carcinoma.
AB  - Because of its high incidence in many of the most populous countries in the
      world, its often fulminant course, poor response to conservative treatment, low
      resectabilty rate when symptomatic, high recurrence rate after resection and
      liver transplantation, and grave prognosis, hepatocellular carcinoma is now
      regarded as one of the major malignant diseases. Hepatocellular carcinoma is the
      most common primary malignant tumour of the liver. Relative to other tumours, it
      ranks fifth in overall frequency (fifth in men and eighth in women) and fourth in
      annual mortality rate. An estimated 372,000 new cases of hepatocellular carcinoma
      are diagnosed each year, constituting 4.6% of all new human cancers (6.3% in men;
      2.7% in women). The annual mortality rate from the tumour is virtually the same
      as its annual incidence. The highest incidences occur in eastern and southeastern
      Asia, some of the Western Pacific islands, and sub-Saharan Africa. Intermediate
      incidences are found in eastern and southern Europe, the Caribbean, Central
      America, and Western Asia. Hepatocellular carcinoma is uncommon in the remaining
      countries. Men are affected more often than are women. The incidence generally
      increases with increasing age, although there is a definite shift towards a
      younger age distribution in black African and ethnic Chinese populations.

PMID- 12505282
TI  - The natural history of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a multistage disease whose occurrence is linked
      to environmental, dietary and life-style factors. Risk factors for HCC have been
      grouped into two clusters, physiologic and pathologic factors. Much evidence
      indicates that these risk factors may interact with each other either as a group
      or as a single factor to modulate development of liver cancer.

PMID- 12505283
TI  - Molecular pathogenesis of human hepatocellular carcinoma.
AB  - Primary hepatocellular carcinoma (HCC) is one of the most common malignancies
      worldwide. However, the viral-chemical etiology as well as molecular mechanisms
      of HCC pathogenesis remains largely unknown. Recent studies in our laboratory
      have identified several potential factors that may contribute to the pathogenesis
      of HCC. Oxidative stress and chronic inflammation have been linked to an
      increased risk of liver cancer. For example, oxyradical overload diseases such as
      Wilson disease and hemochromatosis result in the generation of oxygen/nitrogen
      species that can cause mutations in the p53 tumor suppressor gene. The Hepatitis
      B virus X gene (HBx), a viral transactivator with oncogenic potentials, has been
      shown to bind to and inactivate p53-mediated apoptosis. HBx mutants derived from
      HCC have a diminished ability to act as a transactivator. However, they still
      retain the ability to bind to and abrogate p53-mediated apoptosis. The comparison
      of gene expression profiles between HBx-expressing primary human hepatocytes and
      HBV-infected liver samples by cDNA microarrays indicate a unique alteration of a
      subset of oncogenes and tumor suppressor genes including p53. Our studies
      implicate both viral and endogenous chemical processes in the etiology of HCC,
      and p53 may be a common target for the inactivation during liver carcinogenesis.

PMID- 12505284
TI  - Modes of presentation of chemical neoantigens to the immune system.
AB  - The immune system can interact with small molecular compounds like drugs. Drugs
      are not only immunogenic because of their chemical reactivity, but also because
      they may bind in a labile way to MHC-molecules and fit into available T-cell
      receptors. This seems to be sufficient to stimulate T-cells. Such structural
      features of a drug have to be considered in the evaluation of drug
      hypersensitivity reactions and should be taken into account in predictive drug
      allergy testing.

PMID- 12505285
TI  - The danger hypothesis--potential role in idiosyncratic drug reactions.
AB  - Idiosyncratic or type B reactions are characterised by their unpredictability and
      lack of simple dose-dependency. They occur in a small proportion of patients, and
      usually the predisposing factors are unknown. A proportion of, but not all,
      idiosyncratic reactions are immune-mediated. Our understanding of immune-mediated
      reactions is based on the hapten hypothesis, which requires drug bioactivation,
      covalent binding to proteins, followed by uptake, antigen processing and a
      polyclonal immune response. The recently proposed 'danger hypothesis' can be
      considered to be additive to the hapten hypothesis. The hypothesis states that
      the immune system only responds when it detects danger. If no danger is detected,
      tolerance results. Thus, stimulation of an immune response to a drug-protein
      conjugate (signal 1) requires the presence of co-stimulatory signals and
      cytokines (signals 2 and 3), which propagate and determine the type of immune
      response. The nature of the danger signal is poorly defined, and has been
      proposed to include different forms of stress including chemical, physical and
      viral. Indeed, there are several examples where the frequency of drug
      hypersensitivity is increased in the presence of a viral infection, most notably
      in HIV disease. Nevertheless, this clinical evidence has to be regarded as being
      circumstantial and more direct experimental evidence is required to understand
      the role of 'danger' in the overall pathogenesis of drug hypersensitivity
      reactions.

PMID- 12505286
TI  - Environmental chemicals and autoimmune disease: cause and effect.
AB  - Many important clues have been provided by the relationship of certain
      medications to lupus and other autoimmune syndromes. These are temporary
      conditions that resolve when the medication is removed. There are now over 70
      such medications which have been reported related to these autoimmune conditions.
      Interest continues to grow in the potential for environmental substances to cause
      these syndromes. Among those under suspicion are hydrazines, tartrazines, hair
      dyes, trichloroethylene, industrial emissions and hazardous wastes. Other
      possible associations include silica, mercury, cadmium, gold and L canavanine.
      Two recognised outbreaks include 'toxic oil syndrome' related to contaminated
      rape seed oil in Spain in 1981 and exposure to a contaminated environmental
      substance associated with an autoimmune attack on muscle tissue in 1989.
      Recently, there have been proposals made for the definition and identification of
      environmentally associated immune disorders. The World Health Organisation (WHO)
      has also provided recent publications for other environmentally related problems.
      All these aspects will be presented and reviewed in detail.

PMID- 12505287
TI  - Ultraviolet radiation and autoimmune disease: insights from epidemiological
      research.
AB  - This review examines the epidemiological evidence that suggests ultraviolet
      radiation (UVR) may play a protective role in three autoimmune diseases: multiple
      sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date,
      most of the information has accumulated from population studies that have studied
      the relationship between geography or climate and autoimmune disease prevalence.
      An interesting gradient of increasing prevalence with increasing latitude has
      been observed for at least two of the three diseases. This is most evident for
      multiple sclerosis, but a similar gradient has been shown for insulin-dependent
      diabetes mellitus in Europe and North America. Seasonal influences on both
      disease incidence and clinical course and, more recently, analytical studies at
      the individual level have provided further support for a possible protective role
      for UVR in some of these diseases but the data are not conclusive. Organ-specific
      autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in
      photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these
      processes through several mechanisms which we discuss. In particular, the
      possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3)
      levels in the beneficial immunomodulation of these diseases is discussed.

PMID- 12505288
TI  - Natural and human-made mutagens and carcinogens in the human diet.
AB  - With the exception of tobacco consumption, diet is probably the most important
      factor in the etiology of human cancer, responsible for around one third of all
      cases. Despite strenuous attempts in identification, no single causal factor
      stands out. However, high red meat consumption appears as a potential risk in a
      number of studies and may be important in New Zealand. Mutagens and carcinogens
      may be introduced to meat through preservation methods (N-nitroso compounds) and
      high temperature cooking (heterocyclic amines and polycyclic aromatic
      hydrocarbons). Mutagenic mycotoxins may be introduced to various dietary items
      through disease of livestock (sporidesmin) or of agricultural items leading to
      widespread environmental distribution (e.g. dothistromin). Debates on genetic
      engineering have raised the spectre of dangerous new genetic variants, but there
      is no proof that these have ever occurred. Many carcinogens may be endogenously
      generated. Lifestyle factors such as high alcohol and/or high calorie consumption
      may be important for some members of the population. The consumption of high
      fruits, vegetables and whole grain cereals are likely to be beneficial, but the
      relative roles of dietary fibre, micronutrients and non-nutrients as compared
      with whole foods is under debate. The effects of many of these dietary factors
      are also modulated by genotype. The increasing use of molecular genetic
      techniques, microarrays, proteomics, and the development of human biomonitoring
      methods yield the promise of gaining accurate perspectives on the relative roles
      of different dietary factors and genetic factors in human cancers.

PMID- 12505290
TI  - Diet and prostate cancer.
AB  - The importance of dietary factors for prostate carcinogenesis has been proven by
      epidemiological studies of immigrants from Asia into the USA. Intake of
      foodstuffs rich in fat, including meat, is suggested to be a risk factor.
      Experimentally, while some studies demonstrated high fat intake to promote rat
      prostate carcinogenesis, others did not. Charcoal-cooked red meat and fish have
      been demonstrated to contain heterocyclic amines that are carcinogenic in rodents
      and non-primates. Among them, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) has been shown to induce cancers in the mammary glands, colon and prostate
      of rats. Although there are epidemiological data showing that PhIP could
      contribute to the development of breast cancer, equivalent evidence for prostate
      cancer is lacking. However, as protective dietary factors, micronutrients such as
      selenium, zinc, isoflavones, carotenoids and lycopenes and vitamins E and D have
      been listed. Animal experimentation on prostate cancer has consistently supported
      preventive potential for carotenoids and isoflavones, in contrast to the
      inconsistent results with high fat diets. Although the diet has apparently an
      important influence on prostate carcinogenesis in man, further research is
      necessary for clarification of specific factors in man.

PMID- 12505289
TI  - Novel markers of susceptibility to carcinogens in diet: associations with
      colorectal cancer.
AB  - Red meats cooked at high temperatures generate mutagenic heterocyclic amines,
      which undergo metabolic activation by hepatic cytochrome P450 1A2 and N
      acetyltransferase-2. A primary detoxification pathway involves glutathione S
      transferase A1 (GSTA1), which catalyzes the reduction of the carcinogenic N
      acetoxy derivative back to the parent amine. Recently, we described a
      polymorphism in the GSTA1 proximal promoter; the variant (GSTA1*B) allele
      significantly lowers enzyme expression. In a case-control study, GSTA1*B/*B
      genotype was associated with an increased risk of colorectal cancer, particularly
      among consumers of well-done meat. Dietary nitrosamines, which are bioactivated
      by CYP2A6, represent another potential etiologic factor for colorectal cancer.
      CYP2A6 converts the caffeine metabolite 1,7-dimethylxanthine (17X) to 1,7
      dimethyluric acid (17U); we investigated CYP2A6 activity using the 17U/17X
      urinary metabolite ratio from case-control subjects who completed a caffeine
      phenotype assay. The distribution of CYP2A6 activity was significantly different
      between CRCa cases and controls, with subjects in the medium and high activity
      groups having an increased risk (P for trend=0.001). GSTA1 genotype and CYP2A6
      phenotype should be evaluated as markers of susceptibility to dietary carcinogens
      in future studies.

PMID- 12505291
TI  - A cytogenetic footprint for mammary carcinomas induced by PhIP in rats.
AB  - 2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a mutagen/carcinogen
      belonging to the class of heterocyclic amines (HCAs) found in cooked meats, is a
      mammary gland carcinogen in rats and has been implicated in the etiology of
      certain human cancers including breast cancer. To gain insight into the genomic
      alterations associated with PhIP-induced mammary gland carcinogenesis, we used
      comparative genomic hybridization (CGH) to examine chromosomal abnormalities in
      rat mammary carcinomas induced by PhIP, and for comparison, by DMBA (7, 12
      dimethylbenz[a]anthracene), a potent experimental mammary carcinogen. There was a
      consistent and characteristic pattern of chromosome-region loss in PhIP-induced
      carcinomas that clearly distinguished them from carcinomas induced by DMBA.

PMID- 12505292
TI  - The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in
      monitoring drug safety.
AB  - The Australian adverse drug reaction reporting system is acknowledged as one of
      the best in the world. Despite its small population of less than 20 million
      people, Australia's current ADR reporting rate of over 12,000 reports per year
      places it in the top few nations in terms of reports per capita. The ADRAC
      program has been in operation for over 30 years. Australia was a founding member
      of the WHO International Drug Monitoring Programme which commenced in 1968 and
      currently there are about 153,000 reports in the ADRAC database. Reports from
      health professionals have uncovered a number of significant safety problems over
      the years. Of particular importance are flucloxacillin-induced hepatitis,
      amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with
      tiaprofenic acid. The number and quality of the reports has allowed an
      understanding of the characteristics of the reactions and, using ADRAC reporters
      as a major source of cases, case-control studies have been completed which have
      identified risk factors. ADRAC's review of Australian reports has highlighted
      many important associations that have been disseminated through the Australian
      Adverse Drug Reactions Bulletin.

PMID- 12505293
TI  - Developing a pharmacovigilance system in the Philippines, a country of diverse
      culture and strong traditional medicine background.
AB  - Pharmacovigilance is the study of adverse drug reactions (ADR, events-AE). It
      affords a unique vantage point from which to detect problem drugs and drug use.
      The ADR reporting system in the Philippines was established in August 1994 and
      was recognized as a national centre member of the World Health Organization
      International Drug Monitoring (currently known as the Uppsala Monitoring Centre)
      by February 1995. The pharmacovigilance system in the Philippines developed a
      number of communication and training packages with the intention of advocating
      safer medicines and rational drug use. Although unpopular with western-trained
      medical doctors, people do utilize traditional folk medicines. There have been
      few ADR reports, perhaps in part because the AE are unrecognized; sometimes, the
      AE is misconstrued as part of the healing action; and practitioners of these
      remedies are unlikely to report them. People who resort to herbal medicines are
      usually from the poor segment of the population, and are likely to believe in
      unscientific claims and unlikely to report what they suffered. The promotion of
      herbal medicines as natural safe alternatives neglects the possibility of AE.
      Although unregulated, traditional Chinese medicines are allowed in the
      Philippines if used by ethnic Chinese. The regulation of health supplements has
      also been inefficient. Both of these factors have provided gaps for the entry of
      harmful products. Pharmacovigilance programmes are useful in the detection of
      false claims and substandard medicines. Examples of the Philippine ADR monitoring
      experience are cited.

PMID- 12505294
TI  - Introduction--risk from a philosophy of science point of view.
AB  - In this paper it is argued that risk assessment (RA) should be based on
      principles of philosophy of science. However, in the field of toxicology and the
      associated RA this is generally not the case. The aim of this presentation is to
      demonstrate various principles of philosophy of science, applied to 'risk'.
      Particularly in the context of RA, ignoring basic semantics and methodological
      principles creates unnecessary difficulties and confusion. Better knowledge
      about, e.g. semantics and the role and structure of theories, could help to avoid
      misconceptions and disagreements. We suggest a general theory of risk, which
      makes an attempt to answer the unequivocal question: what is risk?

PMID- 12505295
TI  - Guidelines for application of chemical-specific adjustment factors in
      dose/concentration-response assessment.
AB  - This manuscript addresses guidance in the use of kinetic and dynamic data to
      inform quantitatively extrapolations for interspecies differences and human
      variability in dose-response assessment developed in a project of the
      International Programme on Chemical Safety (IPCS) initiative on Harmonisation of
      Approaches to the Assessment of Risk from Exposure to Chemicals. The guidance has
      been developed and refined through a series of planning and technical meetings
      and larger workshops of a broad range of participants from academia, government
      agencies and the private sector. The guidance for adequacy of data for
      replacement of common defaults for interspecies differences and human variability
      is presented in the context of several generic categories including:
      determination of the active chemical species, choice of the appropriate metric
      (kinetic components) or endpoint (dynamic components) and nature of experimental
      data, the latter which includes reference to the relevance of population, route
      and dose and the adequacy of the number of subjects/samples. The principal
      objective of this guidance developed primarily as a resource for risk assessors,
      is to foster better understanding of the components of and criteria for adequacy
      of chemical-specific data to quantitate interspecies differences and human
      variability in kinetics and dynamics. It is anticipated that this guidance will
      also encourage the development of appropriate data and facilitate their
      incorporation in a consistent fashion in dose-response assessment for regulatory
      purposes (IPCS, 2001).

PMID- 12505296
TI  - Development and implementation of the IPCS conceptual framework for evaluating
      mode of action of chemical carcinogens.
AB  - The framework developed by the International Programme on Chemical Safety (IPCS)
      for assessing the mode of action of tumour induction of chemicals in experimental
      animals has been illustrated with d-limonene, sodium saccharin, di(2
      ethylhexyl)phthalate (DEHP) and sulfamethazine as examples. d-Limonene causes
      renal tumours only in male rats through a response associated with alpha(2u)
      globulin. Sodium saccharin induces urinary bladder tumours only in male rats
      through formation of a urinary precipitate causing erosion of the bladder surface
      and extensive regenerative hyperplasia. DEHP causes liver tumours in rats and
      mice through activation of the receptor PPAR alpha leading to peroxisome
      proliferation and hepatocellular proliferation. Sulfamethazine induces thyroid
      follicular cell tumours in rats and mice through a mechanism involving altered
      thyroid hormone homeostasis.

PMID- 12505297
TI  - The relationship between risk analysis and the precautionary principle.
AB  - Definitions of the precautionary principle (PP) are reviewed with particular
      reference to the role of risk assessment. In general, the PP is employed as a
      means of justifying decisions that are contrary to the conclusions of a formal
      risk assessment. Even where risk assessment is accepted as part of a
      precautionary approach, its importance in subsequent decision-making tends to be
      undermined by application of the PP. The implications for the future of risk
      assessment-based decisions in areas as diverse as environmental protection and
      food safety are briefly considered.

PMID- 12505298
TI  - Transcription factors and cancer: an overview.
AB  - Cancer represents the out-of-control proliferation of a particular cell type,
      which originates with an unwanted mutation, followed by an accumulation of
      defects in many classes of genes. The two well-known types of primary genes that
      govern cell division and are responsible for cancer include: protooncogenes (gain
      of-function) that serve as accelerators to activate the cell cycle, and tumor
      suppressor genes (loss-of-function) that serve as brakes to slow the growth of
      cells. There are now 17 known signal transduction pathways, plus at least two
      stress-response pathways; all of these appear to be highly conserved in
      nematodes, flies and all vertebrates. Ultimately, transcription factors
      participate at the ends of all 19 pathways--by causing the up- or down-regulation
      of specific genes. All primary and modifier genes leading to cancer participate
      in one or another of these pathways. Innumerable exogenous and (autocrine and
      paracrine) endogenous signals bombard our cells each day and all are channeled
      through these 19 pathways, leading to the cell's response to these signals. Tumor
      progression represents a loss of normal cross-talk between cells, breakdown in
      communication between classes of genes, DNA methylation abnormalities, genetic
      instability, and hypermutability. Cancer is thus a multiplex phenotype: a
      crescendo of defects in hundreds if not thousands of genes, as a function of
      time, leading to an invasive and lethal disease.

PMID- 12505299
TI  - Effect of ARA9 on dioxin receptor mediated transcription.
AB  - The dioxin (Aryl hydrocarbon) receptor (DR) is a unique bHLH transcription factor
      which is activated by binding of planar aromatic hydrocarbons typified by dioxin
      (TCDD). The active receptor is key to metabolism of aryl hydrocarbon xenobiotics
      by being a potent inducer of CYP1A1 gene activity. Chlorinated dioxins are inert
      to metabolism and initiate multifarious toxicities, including potent tumour
      promotion. These ill-effects are mediated by the activated DR and we are studying
      the mechanisms by which the ligand binding domain of the DR controls activity of
      the protein. The DR ligand binding domain resides within a PAS (Per/Arnt/Sim
      homology) region which is contiguous with the bHLH. The latent bHLH/PAS dioxin
      receptor (DR) is found in the cytoplasm of most mammalian cell types in a complex
      with heat shock protein 90, a novel immunophilin like protein termed
      ARA9/XAP2/AIP, and the co-chaperone p23. Here we use antisense ARA9 constructs to
      reveal that in the absence of ARA9, the DR is unable to form a transcriptionally
      active complex. Co-expression of antisense ARA9 with a form of the DR which is
      constitutively targeted to the nucleus leads to dramatically decreased levels of
      the nuclear DR protein, implying that ARA9 may function beyond its currently
      proposed role in cytoplasmic retention of the latent DR.

PMID- 12505300
TI  - Estrogenic effects in fish in The Netherlands: some preliminary results.
AB  - Recently, a large-scale field study in The Netherlands has focused on the effects
      of estrogenic contaminants on feral fish populations. The freshwater bream
      (Abramis brama) and the estuarine flounder (Platichthys flesus) were sampled at a
      large number of locations in the spring and autumn of 1999. Concentrations of the
      yolk protein vitellogenin (VTG) in blood plasma of male flounders were small at
      most sites. At two sites, however, moderately elevated concentrations were found
      in autumn. Both sites were situated in the same industrial harbour zone also
      receiving effluent from sewage treatment works. At many sites VTG levels in male
      bream were significantly greater than at the control site. The greatest
      concentrations were observed in individuals collected from a small stream, close
      to the discharge of a relatively large municipal waste water treatment plant.
      This was also the only site where considerable intersex occurred; 37% of male
      bream exhibited ovotestes. Ovotestis was not observed in any of the male flounder
      captured. The results from The Netherlands are briefly discussed and compared
      with the well-known case studies in the UK.

PMID- 12505301
TI  - Affinity of the alligator estrogen receptor for serum pesticide contaminants.
AB  - Top predators, like the American alligator (Alligator mississippiensis)
      bioaccumulate and biomagnify persistent pollutants, such as organochlorine
      pesticides. In a recently published study, several pesticides and pesticide
      metabolites not previously reported in alligator eggs were identified in the
      serum of juvenile alligators. This study examines the affinity of these compounds
      for the alligator estrogen receptor (aER) purified from adult oviductal tissue.
      Of the 11 compounds studied, 9 showed an affinity for the receptor, causing
      greater than 50% displacement of estradiol-17 beta from the aER. The most
      effective compounds were heptachlor epoxide and heptachlor, with IC50 of 19.4 and
      26.7 microM, respectively. Two compounds, aldrin and Mirex showed little affinity
      for the aER. These data suggest that additional compounds are capable of acting
      as aER agonists or antagonists, but future research is needed to confirm in vivo
      actions, if any.

PMID- 12505302
TI  - Reproductive failure and endocrine disruption by organohalogens in fish-eating
      birds.
AB  - Effects of organohalogens in fish-eating birds in the field have been monitored
      largely by studying reproductive outcome in contaminated populations or, at the
      individual level, by studying the sexual behaviour, egg production, or embryonal
      and postnatal development and survival. Endocrine disruption has been suggested
      as a mechanism, but proven cause-effect relationships between specific compounds
      and endocrine disruption with subsequent reduced reproductive outcome in fish
      eating birds are scarce. The effects of organochlorines on hormone metabolism and
      circulating steroid levels are reviewed and discussed in relation to observed
      reproductive failures in the field.

PMID- 12505303
TI  - PCB-induced neurodevelopmental toxicity in human infants and its potential
      mediation by endocrine dysfunction.
AB  - Polychlorinated biphenyls (PCBs) cross the placenta and expose the fetus to the
      body burden of the mother. Additionally, the breastfed baby is postnatally
      exposed to PCBs in maternal milk. Among the broad spectrum of biological effects
      interaction with endocrine systems and developmental neurotoxicity are prominent
      features of these chemical mixtures. Associations between neurodevelopmental
      delay and prenatal or early postnatal PCB-exposure at environmental levels have
      been reported in several cohort studies. Adverse effects were found to be
      associated with early developmental PCB-exposure, although there are
      discrepancies between studies in terms of confounding, effective PCB-matrix, as
      well as spectrum and persistence of effects. From these cohort studies alone the
      causative role of PCBs in producing neurodevelopmental adversity still cannot be
      considered proven, but experimental findings do provide evidence for the
      developmental neurotoxicity of PCBs. The underlying mechanisms of this action is
      still unknown. However, interaction with endocrine systems, namely the
      estrogen/androgen and, particularly, the thyroid hormone systems are discussed as
      a possible explanation for PCB-induced neurodevelopmental adversity. Some
      evidence in this respect is being reviewed.

PMID- 12505304
TI  - PPAR alpha and the regulation of cell division and apoptosis.
AB  - Peroxisome proliferators (PPs) such as the hypolipidaemic drug, nafenopin and the
      phthalate plasticiser 2-diethylhexylphthalate induce rodent hepatocyte cell
      proliferation and suppress apoptosis leading to tumours. PPs act via the nuclear
      hormone receptor peroxisome proliferator activated receptor alpha (PPAR alpha)
      which directly regulates genes implicated in the response to PPs such as the
      peroxisomal gene acyl CoA oxidase. As expected for xenobiotics that perturb
      proliferation, PPs alter expression of cell cycle regulatory proteins. However,
      the ability to alter expression of cyclins and cyclin-dependent kinases is shared
      by physiological hepatic mitogens such as epidermal growth factor and is thus
      unlikely to be specific to the PP-induced aberrant growth associated with
      hepatocarcinogenesis. Recent evidence suggests that the response of hepatocytes
      to PPs is not only dependent upon PPAR alpha but also on the trophic environment
      provided by nonparenchymal cells and by cytokines such as tumour necrosis factor
      alpha. Additionally, the ability of PPs to suppress apoptosis and induce
      proliferation depends upon survival signalling mediated by p38 mitogen activated
      protein kinase. The cross talk between PPAR alpha-mediated transcription,
      survival signalling and cell cycle will be discussed with particular emphasis on
      relevance to toxicology.

PMID- 12505305
TI  - Role of the aryl hydrocarbon receptor in cell cycle regulation.
AB  - One of the most puzzling aspects of the biological impact of polycyclic aromatic
      hydrocarbon compounds is that they elicit an apparently unrelated variety of
      toxic, teratogenic, and carcinogenic responses in exposed animals and in humans.
      At the cellular level, these environmental toxicants affect cell cycle regulatory
      mechanisms and signal transduction pathways in ways that are equally diverse and
      often contradictory. For example, depending on the particular cell lines studied,
      exposure to these compounds may lead to cell proliferation, to terminal
      differentiation, or to apoptosis. These effects are mediated by the aryl
      hydrocarbon receptor, a ligand-activated transcription factor well known for its
      regulatory activity on the expression of several phase I detoxification
      cytochrome P450 genes. Research into the molecular mechanisms of aryl hydrocarbon
      receptor function has uncovered a novel role for this protein during cell cycle
      progression. The activated receptor acts as an environmental sensor and cell
      cycle checkpoint that commits cells exposed to adverse environmental stimuli to
      arrest before the onset of DNA replication.

PMID- 12505306
TI  - Cell cycle control by the thyroid hormone in neuroblastoma cells.
AB  - The thyroid hormone (T3) blocks proliferation and induces differentiation of
      neuroblastoma N2a-beta cells that overexpress the beta 1 isoform of the T3
      receptor. An element in the region responsible for premature termination of
      transcription mediates a rapid repression of c-myc gene expression by T3. The
      hormone also causes a decrease of cyclin D1 gene transcription, and is able to
      antagonize the activation of the cyclin D1 promoter by Ras. In addition, a strong
      and sustained increase of the levels of the cyclin kinase inhibitor (CKI)
      p27(Kip1) are found in T3-treated cells. The increased levels of p27(Kip1) lead
      to a marked inhibition of the kinase activity of the cyclin-CDK2 complexes. As a
      consequence of these changes, retinoblastoma proteins are hypophosphorylated in
      T3-treated N2a-beta cells, and progression through the restriction point in the
      cell cycle is blocked.

PMID- 12505307
TI  - Assessment of persistent and bioaccumulating chemicals in the aquatic
      environment.
AB  - In recent years several national and international organizations have initiated
      actions to control the use and release of persistent, bioaccumulative and toxic
      substances (PBTs). Consequently, a number of criteria have been proposed for the
      classification of these parameters. The scientific bases for PBTs assessment has
      grown a great deal over the last decades. In some specific areas reliable
      predictive capability exists while in other areas considerable uncertainty is
      still present. This paper will briefly point out the achievements and limitations
      of the knowledge on persistence and bioaccumulation with reference to the aquatic
      environment.

PMID- 12505308
TI  - Hazard and risk assessment of chemicals for terrestrial ecosystems.
AB  - Risk assessment for terrestrial ecosystems represents a great challenge due to
      their complexity. Pragmatic approaches, such as independent assessments for soil
      and 'above soil' organisms, are unrealistic. This communication presents a
      workable alternative, extending the role of the hazard identification. For each
      chemical, a set of selected ecological receptors and exposure routes is
      considered. Terrestrial vertebrates, soil-ground-foliar dwelling invertebrates,
      plants, and soil micro-organisms, are potential receptors subjected to direct and
      indirect exposures. Direct exposures cover those related to the emissions during
      the Life Cycle of the chemical. Indirect exposures focus on those occurring after
      the emission, related to the fate and behaviour of the molecule in the
      environment. Direct exposures are regulated by the production-use-disposal
      patterns. Indirect exposures are regulated by intrinsic (physicochemical,
      biological) properties. Hazard identification considers the toxicological profile
      and the exposure potential for each receptor, and selects the key receptors for
      the assessment. Risk analysis includes, for each receptor, all potential exposure
      routes and the corresponding timings. Food chain biomagnification is quantified
      on the basis of toxicokinetic data and a three vertebrate species model, suitable
      for top-predators and humans. A higher tier approach, considering the lack of
      homogeneity of the exposure and probabilistic assumptions, can also be conducted.

PMID- 12505309
TI  - Ecological risk assessment of persistent organic pollutants in the arctic.
AB  - Ecological risk assessment of persistent organic chemicals in marine mammals in
      the Arctic would comprise assessments of both exposure and effect and risk
      characterization. Results from a comprehensive collaborative study between
      Norwegian and Canadian researchers, comprising epizoological (ecological) studies
      (reproductive rate, offspring survival), experimental studies on the immune
      system function, monitoring studies (e.g. physiological assays of thyroid
      hormones, retinol, IgG and testosterone) and registration of biological data
      (e.g. sex, age, reproductive status, nutritional status) were coupled with PCB
      exposure data. Assessment of the results indicates that population status and
      health of polar bears with very high PCB levels may be at risk.

PMID- 12505310
TI  - Receptor-dependent regulation of the CYP3A4 gene.
AB  - A CYP3A4 promoter-reporter gene construct has been used to assess the ability of
      16 known (in vivo) and putative (in vitro) inducers to transactivate a CYP3A4
      reporter gene in HepG2 cells. With the exception of pravastatin, the remaining 15
      compounds transactivated the CYP3A4 reporter gene with differing inductive
      abilities (I(max):EC(50)) over two orders of magnitude, ranging from 1.1
      (phenytoin) to 222.9 (lovastatin) in a receptor-supplemented system and it is
      proposed that the lack of response to pravastatin is due to loss of the known
      hepatic uptake transporter in HepG2 cells. In addition, reporter gene assays were
      used to investigate two promoter mutants namely a T to C change at -191 bp in the
      hepatic nuclear factor 3 binding site (HNF-3, -187 to -194 bp) and an A to G
      change at -205 bp in the oestrogen response element (ERE, -202 to -212 bp), which
      conferred differential responsiveness to steroid and xenobiotic inducers.

PMID- 12505311
TI  - Regulation of P450 4A expression by peroxisome proliferator activated receptors.
AB  - The induction of P450 4A enzymes by peroxisome proliferators (PPs) and fatty
      acids is mediated by the peroxisome proliferator activated receptor alpha (PPAR
      alpha) that binds to response elements in target genes as a heterodimer with the
      retinoid X receptor (RXR). The consensus sequence recognized by PPAR/RXR
      heterodimers, contains an imperfect direct repeat of two nuclear receptor binding
      motifs separated by a single nucleotide. This repeat is preceded by a conserved
      A/T rich sequence that is required for function. In mice, chronic exposure to PPs
      results in PPAR alpha mediated liver hypertrophy, hyperplasia and carcinogenesis
      accompanied by a proliferation of peroxisomes. In contrast, humans exhibit a
      reduced sensitivity to PP pathogenesis. This could reflect >10-fold lower PPAR
      alpha levels relative to mice as well as differences in targeted genes. In order
      to identify PPAR responsive human genes, the human hepatoma cell line, HepG2, was
      engineered to express increased levels of PPAR alpha. Several genes encoding rate
      limiting enzymes and branch points in ketone body formation are regulated by PPAR
      alpha in these cells. In contrast, significant induction by PP is not evident for
      peroxisomal fatty acid oxidation that is associated with peroxisome proliferation
      in mice. Human P450 4A11 is not expressed in dividing cultures of cells with
      enhanced PPAR alpha levels, but it is expressed in confluent cultures expressing
      elevated amounts of PPAR alpha.

PMID- 12505312
TI  - Mechanisms of cytochrome P450 regulation by inflammatory mediators.
AB  - Hepatic levels of cytochrome P450 enzymes and their mRNAs are reduced in models
      of inflammation or infection. The contributions of transcriptional versus post
      transcriptional mechanisms to this decline are poorly understood. The
      transcription of CYP2C11 is rapidly suppressed by administration of bacterial
      endotoxin (lipopolysaccharide, LPS) to rats, consistent with the finding that the
      CYP2C11 promoter contains a negative NF-kappa B response element that confers
      down-regulation of a linked reporter gene by cytokines. Nitric oxide has been
      proposed to be a mediator of inflammatory suppression of P450 expression, but
      reports from different laboratories have disagreed on this subject. Recently, we
      found that LPS suppresses the expression of CYP2B1 by both pre-translational and
      post-translational mechanisms in rat hepatocytes, the latter being NO-dependent
      and occurring only at high concentrations of LPS. Studies were conducted in
      control and NOS2-null mice to determine the contributions of these different
      mechanisms to CYP2B suppression in vivo.

PMID- 12505313
TI  - Mechanisms of arsenic biotransformation.
AB  - Inorganic arsenic, a documented human carcinogen, is methylated in the body by
      alternating reduction of pentavalent arsenic to trivalent and addition of a
      methyl group from S-adenosylmethionine. Glutathione, and possibly other thiols,
      serve as reducing agents. The liver is the most important site of arsenic
      methylation, but most organs show arsenic methylating activity. The end
      metabolites are methylarsonic acid (MMA) and dimethylarsinic acid (DMA). These
      are less reactive with tissue constituents than inorganic arsenic and readily
      excreted in the urine. However, reactive intermediates may be formed. Absorbed
      arsenate (As(V)) is fairly rapidly reduced in blood to As(III), which implies
      increased toxicity. Also, intermediate reduced forms of the methylated
      metabolites, MMA(III) and DMA(III), have been detected in human urine. In
      particular MMA(III) is highly toxic. To what extent MMA(III) and DMA(III)
      contribute to the observed toxicity following exposure to inorganic arsenic
      remains to be elucidated. There are marked differences in the metabolism of
      arsenic between mammalian species, population groups and individuals. There are
      indications that subjects with low MMA in urine have faster elimination of
      ingested arsenic, compared to those with more MMA in urine.

PMID- 12505314
TI  - Oxy radicals, lipid peroxidation and DNA damage.
AB  - Oxygen radicals react with polyunsaturated fatty acid residues in phospholipids
      resulting in the production of a plethora of products, many of them reactive
      toward protein and DNA. One of the most abundant carbonyl products of lipid
      peroxidation is malondialdehyde (MDA), which also is generated as a side-product
      of prostaglandin biosynthesis. It reacts with DNA to form adducts to
      deoxyguanosine, deoxyadenosine, and deoxycytidine. The deoxyguanosine adduct
      (M(1)G) has been detected in liver, white blood cells, colon, pancreas, and
      breast from healthy human beings at levels ranging from 1 to 120 per 10(8)
      nucleotides. Random and site-specific mutagenesis experiments indicate that MDA
      DNA adducts are mutagenic in bacteria and in mammalian cells. M(1)G is highly
      mutagenic when incorporated into viral genomes then replicated in E. coli. It is
      repaired by the nucleotide excision repair pathway. Lipid peroxidation appears to
      be a major source of endogenous DNA damage in humans that may contribute
      significantly to cancer and other genetic diseases linked to lifestyle and
      dietary factors.

PMID- 12505315
TI  - Biological reactivity and biomarkers of the neutrophil oxidant, hypochlorous
      acid.
AB  - Free radicals or reactive oxygen species are thought to contribute to the
      pathology of many diseases. These include inflammatory conditions, where
      neutrophils accumulate in large numbers and are stimulated to produce superoxide
      and other reactive oxidants. Hypochlorous acid (HOCl), produced by
      myeloperoxidase-catalysed oxidation of chloride by hydrogen peroxide, is the
      major strong oxidant generated by these cells. Neutrophil-mediated injury may
      also be important in toxicology when an initial insult is followed by an
      inflammatory response. It is important to characterize the inflammatory component
      of such injury and the extent to which it involves reactive oxidants. On the one
      hand, this requires an understanding of how neutrophil oxidants react with cells
      and tissue constituents. On the other, specific biomarkers are needed so that
      oxidative damage can be quantified in clinical material and related to disease
      severity. This presentation considers biologically relevant reactions of HOCl and
      the biomarker assays that can be applied to probing the pathological role of
      myeloperoxidase and its products.

PMID- 12505317
TI  - Transgenic models in xenobiotic metabolism and toxicology.
AB  - There exist in animals a large number of enzymes that primarily metabolize
      xenobiotics including drugs, toxins and carcinogens. While these enzymes are
      known to activate or inactivate toxins and carcinogens in vitro, it had not been
      demonstrated until recently whether they are responsible for the biological
      effects of these chemicals in intact animal models. In order to determine the
      biological affects of xenobiotic-metabolizing enzymes, gene knockout mice were
      made that lack expression of certain P450s (CYP1A1, CYP1A2, CYP1B1 and CYP2E1),
      microsomal and cytosolic epoxide hydrolases, and NADPH:quinone oxidoreductase.
      These mice have no deleterious phenotypes indicating that xenobiotic-metabolizing
      enzymes have no direct role in mammalian development and physiological
      homeostasis even though all the genes and enzymes examined are conserved in
      mammals. However, in many cases, mice lacking certain xenobiotic-metabolizing
      enzymes confer resistance to acute toxicities and chemical carcinogenesis thus
      demonstrating that these enzymes mediate the deleterious effects of chemicals.
      The use of xenobiotic metabolism null animal models to study the mechanisms of
      actions of toxins and carcinogens will be reviewed.

PMID- 12505316
TI  - Aldehyde-sequestering drugs: tools for studying protein damage by lipid
      peroxidation products.
AB  - Elevated levels of reactive alpha,beta-unsaturated aldehydes (e.g.
      malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of
      various degenerative conditions suggest these substances are active propagators
      of the disease process. One experimental approach to attenuating damage by these
      intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles,
      thereby sparing cell macromolecules and perhaps slowing disease progression.
      Drugs with demonstrated trapping activity toward lipid-derived aldehydes include
      various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We
      have focused on identifying scavengers of acrolein, perhaps the most toxic
      aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds
      (hydralazine and dihydralazine) were found to trap acrolein readily, forming
      hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly
      protect against acrolein-mediated toxicity in isolated hepatocytes.

PMID- 12505318
TI  - Evaluation on carcinogenicity of chemicals using transgenic mice.
AB  - Since new guidelines on ICH carcinogenicity testing of pharmaceuticals have been
      adopted, evaluation on carcinogenicity of newly-developed pharmaceuticals using
      genetically modified animals has been conducted. Validation studies have
      suggested that rasH2 mice carrying human prototype c-Ha-ras gene, heterozygous
      p53 deficient [p53 (+/-)] mice and homozygous XPA deficient [XPA (-/-)] mice are
      very susceptible to genotoxic carcinogens. In addition, many experimental studies
      using rasH2 and p53 (+/-) mice in our laboratory suggest that these mouse models
      are very useful for clarifying the mechanism of organ-specific carcinogenesis. On
      the other hands, there are unsolved mechanisms and points that need to be
      clarified in these models, as described below. (1) The mechanism of the enhanced
      carcinogenesis is not completely understood; point mutations of human prototype c
      Ha-ras gene are not always related to the tumor induction in rasH2 mice, but
      recent studies demonstrated that overexpression of the transgene is responsible
      for the enhanced carcinogenesis. (2) Malignant lymphomas are induced by the
      treatment of phenolphthalein in p53 (+/-) C57Bl/6 mice, in which exon 5 of the
      lateral p53 allele was inactivated, but not in p53 (+/-) CBA and C57Bl/6 mice, in
      which exon 2 of the p53 allele was inactivated. In this respect, such a strain
      difference and different genetically engineering procedure should be taken into
      account when p53 (+/-) mice are planned to be used for the evaluation of
      carcinogenic potential of newly-developed chemicals.

PMID- 12505319
TI  - Promotion of organophosphate induced delayed polyneuropathy by certain esterase
      inhibitors.
AB  - Organophosphate induced delayed polyneuropathy (OPIDP) is an axonopathy caused by
      single doses of some organophosphates (OPs). Other OPs, sulphonyl halides,
      carbamates, thiocarbamates and phosphinates do not cause axonopathy but elicit or
      intensify the clinical expression of OPIDP when given after a neuropathic OP
      (promotion of OPIDP). One enzymatic activity (M200) was identified by means of
      selective inhibitors in hen peripheral nerve crude homogenates. Promotion of
      OPIDP initiated with several OPs was found to correlate with inhibition of M200
      when various promoters were given to hens. Most M200 is in the soluble fraction
      of peripheral nerves and was separated from other esterases by means of molecular
      exclusion chromatography. In a second series of experiments, inhibition of this
      fraction also correlated with promotion when induced by the same chemicals.
      Further ion exchange chromatography identified a protein (60 kDa MW): the
      inhibition of its enzymatic activity correlated with promotion in another series
      of in vivo experiments. Biochemical and structural analyses of this protein are
      underway. Several experiments indirectly suggest that promotion may be related to
      mechanisms of repair and/or compensation of peripheral nerves. These include the
      observation that promotion results in clinical expression of biochemical lesions
      that otherwise would be well compensated, that promotion is not specific because
      axonopathies of other etiology are also exaggerated, and that promoters are
      effective when given several days before the neuropathic insult. Moreover,
      developing animals are more resistant to promotion.

PMID- 12505320
TI  - Insights into a basis for incomplete inhibition by botulinum toxin A of Ca2+
      evoked exocytosis from permeabilised chromaffin cells.
AB  - Inhibition of regulated exocytosis by botulinum toxins type A and B was studied
      in chromaffin cells. Both virtually abolished catecholamine release triggered
      from intact cells by depolarising stimuli, whereas the blockade by type A, but
      not B, was only partial after cell permeabilisation and direct stimulation of
      exocytosis by Ca(2+). Botulinum toxin A did not alter the [Ca(2+)]-dependency of
      exocytosis in permeabilised cells but, rather, proportionally reduced the amount
      of release at each concentration tested. Likewise, this toxin decreased the
      extents of Ca(2+)-induced structural changes in SNAP-25, synaptobrevin and
      syntaxin (known collectively as SNAREs), whilst leaving their [Ca(2+)]
      sensitivity unaltered. Thus, botulinum toxin A does not reduce the Ca(2+)
      sensitivity of the exocytosis sensor, but hinders transmission of the signal to
      the SNAREs which mediate fusion.

PMID- 12505321
TI  - Genetically-engineered bacteria expressing human enzymes and their use in the
      study of mutagens and mutagenesis.
AB  - Expression of human enzymes in bacterial cells has made possible the development
      of a new generation of mutagenicity assays. Metabolic activation takes place
      within the internal milieu of the target cell, so that no membrane barrier is
      interposed between the reactive metabolite and the DNA target. This technology
      has been extended to all major classes of enzymes of xenobiotic
      biotransformation, including P450. Expression of sequence variants of mutagen
      bioactivation enzymes provides a new tool for studying their structure and
      function.

PMID- 12505322
TI  - Use of heterologously-expressed cytochrome P450 and glutathione transferase
      enzymes in toxicity assays.
AB  - Our groups have had a long-term interest in utilizing bacterial systems in the
      characterization of bioactivation and detoxication reactions catalyzed by
      cytochrome P450 (P450) and glutathione transferase (GST) enzymes. Bacterial
      systems remain the first choice for initial screens with new chemicals and have
      advantages, including high-throughput capability. Most human P450s of interest in
      toxicology have been readily expressed in Escherichia coli with only minor
      sequence modification. These enzymes can be readily purified and used in assays
      of activation of chemicals. Bicistronic systems have been developed in order to
      provide the auxiliary NADPH-P450 reductase. Alternative systems involve these
      enzymes expressed together within bacteria. In one approach, a lac selection
      system is used with E. coli and has been applied to the characterization of
      inhibitors of P450s 1A2 and 1B1, as well as in basic studies involving random
      mutagenesis. Another approach utilizes induction of the SOS (umu) response in
      Salmonella typhimurium, and systems have now been developed with human P450s 1A1,
      1A2, 1B1, 2C9, 2D6, 2E1, and 3A4, which have been used to report responses from
      heterocyclic amines. S. typhimurium his reporter systems have also been used with
      GSTs, first to demonstrate the role of rat GST 5-5 in the activation of
      dihalomethanes. These systems have been used to compare these GSTs with regard to
      activation of dihaloalkanes and potential toxicity.

PMID- 12505323
TI  - Modeling the metabolic competency of glutathione S-transferases using genetically
      modified cell lines.
AB  - Certain chemopreventive agents are thought to work in part via induction of GST
      expression. We have utilized transgenic cell lines to show that GST expression
      can protect against DNA alkylation, and in some cases cytotoxicity caused by
      electrophilic carcinogens conjugated by GSTs (e.g. 4-NQO, B[a]P, DiB[a,l]P,
      AFB(1), and certain drugs). However, factors governing protection by GST are
      complex and vary with different agents and end-points. For example, expression of
      GST alone was sufficient for partial protection against DNA alkylation by 4-NQO,
      but protection against 4-NQO cytotoxicity was only observed when the ATP
      dependent GS-X transport protein MRP1 was also co-expressed. The dynamic
      competition between activation and detoxification is the focus of current studies
      in cells that co-express both CYP1A1 and either hGSTP1 or hGSTM1. Expression of
      hGSTP1 largely blocked B[a]P toxicity induced via the moderate activation by rat
      or human CYP1A1. With DiB[a,l]P, GSTs gave up to 7-fold protection against
      toxicity only when activated by human CYP1A1. However, cells with CYP1A1+GST
      remained at least 20-fold more sensitive to DiB[a,l]P than parent cells lacking
      either activity, due to strong activation by hCYP1A1. In summary, we have found
      that protection by GSTs against B[a]P or DiB[a,l]P toxicity is highly variable
      depending on differences in: (a) the PAH structure; (b) the human vs. rat CYP1A1
      expressed; (c) GST isozyme(s) expressed; (d) cellular expression of conjugate
      transporters; or (e) DNA damage versus cytoxicity end-points.

PMID- 12505324
TI  - Incorporating mechanistic data into risk assessment.
AB  - Incorporating mechanistic data into risk assessment is intended to improve the
      overall scientific validity, and thereby reduce the uncertainty, in human risk
      analysis. Relevant mechanistic data provides a link between the molecular and
      cellular event(s) and adverse outcome, and insight into mechanism of action is
      critical for accurate evaluation of dose-response relationships and inter-species
      extrapolation. This paper provides an example of applying mechanistic data to
      human risk assessment using the frameworks outlined by the International
      Programme on Chemical Safety (IPCS) and the U.S. Environmental Protection Agency
      (USEPA). Key components of the data are used to address the strength and
      consistency of the mechanism and to apply these data to human risk
      characterization.

PMID- 12505325
TI  - The use of biologically based modeling in risk assessment.
AB  - Technological advances are rapidly leading toxicology and risk assessment to an
      age where there are advantages of routine use of biologically based modeling as
      an adjunct to laboratory experiments will be compelling. The biologically based
      model, a formal representation of the system being studied, serves both the
      experimentalist and the risk assessor. Benefits of its development include
      identification of data gaps, optimization of experimental design and, with
      sufficient validation, quantitative extrapolations between routes of exposure,
      species and doses. This article focuses on the role of biologically based
      modeling in support of the dose-response assessment component of risk assessment.
      The problem of uncertainty in dose-response assessment and the role of
      mechanistic studies combined with modeling to efficiently reduce uncertainty are
      discussed. The need for close cooperation between experimentalists, modelers, and
      risk assessors to achieve this efficiency is emphasized. A model for formaldehyde
      is briefly described to illustrate key issues.

PMID- 12505326
TI  - EU risk assessment: science and policy.
AB  - The EU risk assessment programme on existing substances is governed by Council
      Regulation (EC) 793/93. This regulation sets out a framework for evaluating and
      controlling the risks posed by existing substances. The results of the EU risk
      assessment programme are science-based regulatory risk assessments. This paper
      gives an overview of some fundamental principles governing the EU existing
      substances risk assessment programme, focusing on where and why there may be gaps
      between science and policy. Examples are then given showing that EU regulatory
      decisions are based on science, but also illustrating how policy influences the
      regulatory decisions.

PMID- 12505327
TI  - Toxicological implications of hepatobiliary transporters.
AB  - Recent progress in molecular biological research has revealed that many types of
      transporters are expressed in the liver. Such xenobiotic transporters have a wide
      range of substrate specificity, which allows them to act as a barrier to protect
      the body from potentially harmful xenobiotics. Most of them mediate active
      transport of the substrates, leading to concentrative uptake and excretion into
      the hepatocytes and bile. Transport properties such as these may play a role in
      the toxicity of certain types of substrates. For example, anticancer agents such
      as methotrexate and irinotecan are efficiently excreted into the bile and such
      excretion has been suggested to account for their toxic gastrointestinal side
      effects. A similar hypothesis has also been proposed for NSAIDs. Considering
      their tissue-specific expression, these transporters also appear to be a
      promising target for the delivery of small molecules, while simultaneously
      minimizing their side-effects. For example, transporters involved in the oral
      absorption, hepatic uptake, and biliary excretion of pravastatin, an HMG-CoA
      reductase inhibitor, ensure its enterohepatic circulation giving it an important
      pharmacokinetic advantage since its pharmacological target is the liver. Of the
      major ACE inhibitors currently available, temocaprilat is a substrate of hepatic
      transporters. Since the major elimination route for other ACE inhibitors is via
      urinary excretion, their plasma concentrations exhibit a high degree of inter
      patient variability over a wide range of renal function whereas the
      concentrations of temocaprilat exhibit a much lower degree of inter-patient
      variability due to its elimination into the bile. Thus, the hepatobiliary
      transporters are involved in some aspects of toxicology and, therefore, a
      rational strategy for regulating the recognition by such transporters may be
      required for optimum drug design. This presentation will discuss the possible
      role of hepatic transporters from a toxicological point of view.

PMID- 12505328
TI  - Transporters and xenobiotic disposition.
AB  - Metabolism alone does not adequately account for the observed intersubject
      variability in drug disposition or response. Carrier-mediated processes, or
      transporters, are increasingly recognized to be importantly involved in drug
      absorption, distribution, and excretion. Thus for many drugs, transport and
      metabolism must be considered together to better predict drug disposition in
      vivo. Accordingly, this review will outline relevant background information
      regarding drug transporters and the role of such transporters in the drug
      disposition process.

PMID- 12505329
TI  - Genetically determined differences in P-glycoprotein function: implications for
      disease risk.
AB  - The MDR1 gene product P-glycoprotein does not only contribute to drug resistance
      during chemotherapy of tumors but it is also expressed in healthy tissues with
      excretory function (intestine, liver and kidney). It transports a wide range of
      structurally unrelated compounds out of cells. Intestinal expression of this
      transporter has been shown to determine bioavailability of orally administered P
      glycoprotein substrates such as digoxin. Recently, several mutations were found
      in the MDR1 gene. Subjects homozygous for the C3435T mutation (24% of Caucasians)
      have low intestinal P-glycoprotein levels, high plasma concentrations after oral
      digoxin and a reduced P-glycoprotein function in peripheral blood cells in
      comparison to the remainder of the population. Potential implications of this
      reduced mechanism of detoxification will be shown for three selected diseases:
      (1) association of low intestinal P-glycoprotein expression with development of
      inflammatory bowel disease; (2) implications for disease risk and therapeutic
      outcome of HIV; and (3) consequences of this mutation for renal P-glycoprotein
      expression and risk of renal cell carcinoma.

PMID- 12505330
TI  - Respiratory allergy: what are the uncertainties?
AB  - The prevalence of asthma is increasing worldwide. The increase has been found for
      both sexes, for all races and age groups. The factors responsible are unclear.
      The short period of increase makes it unlikely that a genetic change is
      responsible but rather suggests that either air pollutants or a behavioral change
      may be involved. Behavioral changes may include decreased exercise and outdoor
      activity due to, for example increased usage of television and computers. What is
      the role of allergy in the development of asthma? In allergic sensitization,
      allergens initiate the inflammation and IgE antibodies are typically present.
      Once asthma has developed, factors such as irritants, infections and exercise may
      result in acute symptomatology. Infancy is a high risk period for allergic
      sensitization since natural defense mechanisms are not fully developed.
      Epidemiologic evidence suggests that microbial stimuli during early childhood can
      influence induction of atopic diseases. In animal studies, pre-infection with
      respiratory virus has resulted in enhanced response to allergens. Another factor
      implicated in the surge of allergic disease is airborne particulates. Evidence
      has been obtained for an association of environmental tobacco smoke (ETS) with
      development of allergic sensitization. ETS enhances IgE production as does diesel
      and aluminum silicate, the latter a component of fly ash. What are the mechanisms
      responsible for the environmental influences on development of allergy? Th2
      cytokine responses, with suppression of Th1 cytokines, are prominent in children.
      Th1 maturation appears to be promoted by microbial exposure. Increased
      understanding of the complex interactions of environmental factors with the
      developing immune system is essential to reverse the current upward trend in
      allergic respiratory disease.

PMID- 12505331
TI  - Chemical respiratory allergy: role of IgE antibody and relevance of route of
      exposure.
AB  - Chemicals are able to cause various forms of allergic disease in susceptible
      individuals. Among those of greatest importance in the context of occupational
      disease is chemical respiratory allergy, where allergic sensitization of the
      respiratory tract is associated with elicitation of rhinitis, asthma and/or other
      pulmonary symptoms following inhalation exposure to the inducing chemical
      allergen. Although for some chemical respiratory allergens (including the acid
      anhydrides) there exists a strong correlation between symptoms and the presence
      of specific IgE antibody, for other respiratory sensitizers (and notably the
      diisocyanates) such an association is variable or absent. These data have
      resulted in speculation about a universal mandatory role for specific IgE
      antibody in the induction and elicitation of respiratory allergy to chemicals and
      of the nature of alternative or complementary mechanisms of sensitization. There
      is debate also regarding the routes through which exposure to relevant chemical
      allergens may result in the acquisition of respiratory sensitization. Although
      inhalation exposure is probably the most common and most important route through
      which allergic sensitization of the respiratory tract is achieved, there is
      evidence also that respiratory sensitization to chemicals may be acquired also by
      dermal contact; observations that have important implications for occupational
      health management. The significance of IgE antibody and dermal exposure in the
      context of occupational respiratory allergy to chemicals is discussed.

PMID- 12505332
TI  - Pollution, environmental factors and childhood respiratory allergic disease.
AB  - Epidemiologic studies have shown that hay fever and asthma in children have
      increased over the last 50 years. Experimental data have suggested that exposure
      to environmental substances such as diesel exhaust particles can induce
      production of allergen specific IgE antibodies, while exposure to other
      substances such as endotoxins may rather induce non-allergic immune responses and
      suppress IgE production. The end of the East-West division of Europe provided the
      opportunity to assess the effect of different environmental conditions on the
      development of allergies. Differences in exposure to possible risk factors and
      their effect on allergic sensitisation in early life, a period considered
      critical for the development of persistent IgE reactions, are particularly
      important to analyse. Cars, NO(2) and NO exposure were more prevalent in Western
      Europe, while pollution by heavy industry and coal heating were present in
      Eastern cities. The results of population based comparisons have produced little
      evidence of air pollution causing new cases of allergy in children, and it seems
      rather unlikely than an excess in external toxic exposure is responsible for the
      world wide increase in pediatric atopy. However, some studies analysing local
      traffic exposure (in particular truck traffic) have found an increased allergy
      prevalence at least in subgroups of children. While a link between the inception
      of new allergies and air pollutants has to date not been convincingly shown, the
      increased respiratory morbidity associated with such exposure in children with
      established asthma as well as healthy children does result in considerable health
      costs.

PMID- 12505333
TI  - Influences on the development of allergy and asthma.
AB  - A number of factors contribute to development of asthma and allergy in humans.
      Genetic factors clearly play a role in development of asthma and allergy.
      However, recent studies suggest that westernized lifestyle, perhaps certain
      pollutants, and less frequent exposure to microbes may allow for allergy to
      develop. It is the interactions of risk genes with urbanized environments that
      lead to development of allergy. Recent studies suggest that the most significant
      period of development of allergy is in early childhood, with additional data
      suggesting that a tendency for mononuclear cells to produce Th2 cytokines exists
      in early childhood. Reviewed in this article are genetic, inflammatory and
      lifestyle factors which contribute to development of allergy in childhood.

PMID- 12505334
TI  - Setting ambient air quality standards for particulate matter.
AB  - Ambient air particulate matter (PM), unspecified as to chemical composition, is
      of concern because of its health effects. Air quality standards for PM have been
      established in many countries. The earliest standards were based on threshold
      models and use of a margin of safety. Initially, standards were based on the mass
      of total suspended material. In the 1980s a shift to a size-specific standard,
      PM(10), began. PM(10) is the fraction of PM captured with 50% efficiency at 10
      microm and greater efficiency at smaller sizes. In the late 1990s, standards were
      proposed for PM(2.5), which is captured with 50% efficiency at 2.5 microm. The
      standards for PM are based almost exclusively on human epidemiological data, with
      laboratory animal and in vitro data used in a supporting role. During the 1990s,
      new statistical tools began to be used and demonstrated an association between
      increased PM and an increase in cardiorespiratory morbidity and mortality. The
      analyses are complicated by the effects of other pollutants such as ozone.
      Effects have been observed down to 10-20 microg of PM(10) per cubic meter, levels
      equal to or below background in many parts of the world. In many studies there
      has been no evidence of a threshold. In the absence of a threshold, a critical
      issue becomes how to determine how low is low enough? This paper reviews the
      current literature on PM health effects and suggests research avenues that may
      yield data which, combined with public policy considerations, may be able to
      address the issue of 'how low is low enough?'

PMID- 12505335
TI  - Health effects of diesel exhaust emissions--a mixture of air pollutants of
      worldwide concern.
AB  - Diesel exhaust is a mixture of particles and gases. It contains more than several
      hundred different organic and inorganic components, including many chemicals that
      have been designated as toxic air pollutants. Because mutagens and carcinogens
      are present in both the gaseous and particulate components, lung cancer has been
      the focus of attention as a health risk in animal and human research. Moreover,
      since the epidemiologic data suggest carcinogenicity in humans, and the diesel
      exhaust exposure data in evaluations in rats by NIOSH, IARC, WHO, and the
      California EPA, are said to demonstrate or support carcinogenicity, agencies have
      designated them as latent occupational carcinogens (NIOSH) or toxic air
      pollutants (California EPA). In regard to their non-carcinogenic effects, a
      contribution to airway inflammation and allergies, and in relation to disease,
      the possibility of contracting asthma and chronic bronchitis, have been
      investigated both experimentally and epidemiologically, and concern has increased
      about their health effects, particularly in children.

PMID- 12505336
TI  - A European perspective on hazardous air pollutants.
AB  - Air pollution is considered to be a major threat to human health. Protection of
      human health from adverse effects of air pollutants and elimination or reduction
      of exposure to hazardous air pollutants was therefore the major consideration of
      the World Health Organization to establish the Air Quality Guidelines for Europe.
      The 2nd edition of the WHO guidelines has recently been published. In
      establishing pollutant levels below which exposure does not constitute a
      significant public health risk, the guidelines provide information for regulatory
      authorities on a national or international level to set standards or limit values
      for air pollutants. The guidelines also form a basis for the development of risk
      management or risk abatement strategies. During the recent revision of the WHO
      Air Quality Guidelines for Europe, DG Environment of the European Commission
      developed a Framework Directive on Air Quality (96/62/EC) and a number of
      Daughter Directives dealing with individual pollutants. It was agreed that the
      European Commission should use the WHO Air Quality Guidelines as starting point
      for deriving limit values for a number of major air pollutants in the European
      Union. This paper describes the revision of the WHO guidelines and addresses the
      differences between guidelines and legally binding standards as for instance the
      limit values established by the EU.

PMID- 12505337
TI  - Evaluating hazardous air pollutants in Australia.
AB  - Hazardous air pollutants (HAPS) have been evaluated for their health and
      environmental significance on a targeted and campaign basis in Australia until
      recently. Individual States and Territories have been undertaking targeted
      monitoring studies and have numerous control strategies aimed at controlling HAPS
      emissions with the focus largely on volatile organic compounds (VOCs), polycyclic
      aromatic hydrocarbons (PAHs) and selected heavy metals, with some limited work on
      exposure assessment. There has been little evaluation of the potential health or
      environmental effects of the monitored concentrations of these substances and few
      toxicological or epidemiological studies have been conducted-none in the
      community setting in Australia. Moreover, there has not been an agreed method for
      assessing risks from HAPS in ambient air, with different jurisdictions utilising
      different international benchmarks. Recently, the National Environmental Health
      (EnHealth) Council commenced developing a risk assessment methodology, which is
      being used in the development of ambient air quality guidelines for selected HAPS
      in Western Australia. In 1999, the Commonwealth Government established the Living
      Cities-Toxics Program, designed to assess the state of knowledge on HAPS in
      Australia with the aims of identifying and prioritising HAPS, identifying
      information gaps and informing the development of national air quality standards
      and national management strategies. The Commonwealth Government commenced a
      number of projects in 2000 to progress these aims.

PMID- 12505338
TI  - Hazard identification and risk assessment of endocrine disrupting chemicals with
      regard to developmental effects.
AB  - Endocrine Disrupting Chemicals (EDC) may affect mammalian development either
      indirectly (by affecting implantation, placenta, lactation, etc.) or directly,
      altering the maturation of target tissues. Studies on reproductive and
      developmental effects are likely to provide the critical information for risk
      assessment of most EDC, when proper endpoints are investigated. Toxicity testing
      guidelines, and especially the two-generation test, are currently being updated
      with regard to risk assessment of EDC. Particular emphasis is put on selection
      and validation of the parameters most sensitive to given chemicals and/or
      mechanisms of action; therefore, a screening battery it is important to address
      further testing. Under this respect the future use of gene arrays might be a most
      promising development, when more data will be available. Further points to be
      considered in a biologically-based assessment of developmental risks include: the
      identification of critical effects also through the evaluation of dose-response
      curves; the assessment of the actual exposure and different susceptibility of
      target tissues; the identification of possible factors of susceptibility and gene
      environment interactions; the elaboration of models to estimate the possible
      additional risk deriving from combined exposures to EDC having similar mechanisms
      and/or targets.

PMID- 12505339
TI  - Xenoendocrine disrupters-tiered screening and testing: filling key data gaps.
AB  - The US Environmental Protection Agency (EPA) is developing a screening and
      testing program for endocrine disrupting chemicals (EDCs) to detect alterations
      of hypothalamic-pituitary-gonadal (HPG) function, estrogen (ER), androgen (AR)
      and thyroid hormone synthesis and AR and ER receptor-mediated effects in mammals
      and other animals. High priority chemicals would be evaluated in the Tier 1
      Screening (T1S) battery and chemicals positive in T1S would then be tested (Tier
      2). T1S includes in vitro ER and AR receptor binding and/or gene expression, an
      assessment of steroidogenesis and mammalian (rat) and nonmammalian in vivo assays
      (Table 1). In vivo, the uterotropic assay detects estrogens and antiestrogens,
      while steroidogenesis, antithyroid activity, (anti)estrogenicity and HPG function
      are assessed in a 'Pubertal Female Assay'. (Anti-) androgens are detected in the
      Hershberger Assay (weight of AR-dependent tissues in castrate-immature-male
      rats). Fish and amphibian assays also are being developed. The fathead minnow
      assay can identify EDCs displaying several mechanisms of concern, including AR
      and ER receptor agonists and antagonists and inhibitors of steroid hormone
      synthesis. An amphibian metamorphosis assay is being developed to detect thyroid
      active substances. Several alternative mammalian in vivo assays have been
      proposed. Of these, a short-term pubertal male rat assay appears most promising.
      An in utero-lactational screening protocol also is being evaluated. For Tier 2,
      the numbers of endocrine sensitive endpoints and offspring (F1) examined in
      multigenerational tests need to be expanded for EDCs. Consideration should be
      given to tailoring T2, based on the results of T1S. Tier 1 and 2 also should
      examine relevant mixtures of EDCs. Toxicants that induce malformations in AR
      dependent tissues produce cumulative effects even when two chemicals act via
      different mechanisms of action.

PMID- 12505340
TI  - Ecological risk assessment and testing for endocrine disruption in the aquatic
      environment.
AB  - Field observations of endocrine disruption (ED) in fish and other aquatic species
      have contributed to a global effort to establish test methods for detecting ED
      effects in wildlife species. For ecological risk assessment, validated tests are
      needed for Amphibia, fish and aquatic invertebrates, supported by a tiered
      approach incorporating mechanistic data and exposure characterisation. The
      potential for extrapolation of ED data from mammalian to aquatic species may be
      limited, however, due to significant physiological differences in function and
      regulation of hormone systems in (aquatic) lower vertebrates and invertebrates.
      Presently, the OECD is considering a tiered approach for ED risk assessment,
      incorporating a fish 14-day screening assay (Tier 1); fish development and
      reproduction tests (both Tier 2); and a fish full life-cycle test (Tier 3). For
      detection of (anti-)oestrogens, the yolk-precursor protein vitellogenin is an
      ideal biomarker of exposure and functionally equivalent biomarkers are being
      sought for (anti-)androgens in fish. At the two higher tiers, impacts are
      assessed in terms of apical endpoints (e.g. development, breeding behaviour and
      fecundity) and also gonadal histopathology. Validation of these higher tier tests
      should include comparison of sensitivity of biochemical and apical endpoints to
      optimise the value of biomarkers for predicting adverse health effects (e.g.
      impaired reproduction). The specificity of future OECD fish and amphibian test
      guidelines for endocrine disrupters needs further consideration through inclusion
      of mechanistic endpoints based on state-of-the-art molecular endocrinology.

PMID- 12505341
TI  - Scientific issues associated with the validation of in vitro and in vivo methods
      for assessing endocrine disrupting chemicals.
AB  - The assays required to assess the potential of chemicals to act as endocrine
      disrupting (ED) agents are either in place or are under current development.
      However, the validation and utilisation of these assays is currently being
      hampered by uncertainties regarding their purpose and required sensitivity, and
      uncertainties as to the intrinsic variability of the parameters being measured.
      This article discusses these several sources of uncertainty and the intrinsic
      variability of many of the key assay parameters. It is concluded that current
      uncertainties regarding the use of ED assays, and the extrapolation of rodent
      effects to humans, are due to the absence of an extensive agreed rodent control
      database for the developmental parameters under study, coupled to the established
      intrinsic variability of these parameters between strains/species of test animals
      and test protocols. Only when these factors are generally accepted, well studied
      and controlled for, will it be possible to employ ED assays with confidence and
      to relate assay data to effects likely to be seen in humans.

PMID- 12505342
TI  - Environmental epidemiology: basics and proof of cause-effect.
AB  - Bringing epidemiology and toxicology together to better understand cause and
      effect relationships requires attention to several interconnected problems:
      problems of commitment, complexity, and of communication. The most fundamental of
      these is commitment as it is reflected in the basic purpose of environmental
      epidemiology. The purpose of epidemiology is not to prove cause-effect
      relationships, and not only because scientific proof is elusive. The purpose of
      epidemiology is to acquire knowledge about the determinants and distributions of
      disease and to apply that knowledge to improve public health. A key problem,
      therefore, is how much and what kinds of evidence are sufficient to warrant
      public health (typically preventive) actions? The assessment of available
      evidence lays the foundation for the problem of complexity: relevant evidence
      arrives from toxicologic and epidemiological investigations, and reflects the
      acquisition of knowledge from many levels of scientific understanding: molecular,
      cellular, tissue, organ systems, complete organisms (man and mouse),
      relationships between individuals, and on to social and political processes that
      may impact human health. How to combine evidence from several levels of
      understanding will require the effective communication of current methodological
      practices. The practice of causal inference in contemporary environmental
      epidemiology, for example, relies upon three largely qualitative methods:
      systematic narrative reviews, criteria-based inference methods, and
      (increasingly) meta-analysis. These methods are described as they are currently
      used in practice and several key problems in that practice are highlighted
      including the relevance to public health practice of toxicological evidence.

PMID- 12505343
TI  - Case studies in the use of toxicological measures in epidemiological studies.
AB  - One of the major limitations in environmental epidemiological studies
      investigating associations between chemical exposures and the risk of disease is
      the use of crude exposure metrics. This increases the risk of exposure
      misclassification, reducing the chance of finding a real association, where one
      exists. In environmental epidemiological studies, surrogate exposure measures,
      such as time living in a contaminated area, do not adequately reflect the true
      nature and/or degree of real exposure to the chemical substance(s) of interest.
      Also, as they are not quantitative measures of absorbed dose, the data provided
      by such measures cannot give numerical measures of a dose response relationship,
      limiting their use in quantitative risk assessment. In epidemiological studies,
      biological measures of exposure should be used, if available, as they are close
      to the target organ dose and provide greater precision in risk estimates and dose
      response relationships. Examples are the measurement of speciated arsenic in the
      urine of subjects when investigating health effects from arsenic exposure, and
      the use of breast milk lipid concentration to measure body burden when conducting
      epidemiological studies of health effects from persistent lipophilic compounds,
      such as the endocrine disruptors. This paper discusses the main uses of such
      exposure measures, using several case studies, their limitations and some
      challenges in the future for toxicologists to develop more suitable measures for
      epidemiologists to use in population studies.

PMID- 12505344
TI  - Biomarkers of genetic damage for cancer epidemiology.
AB  - Cancer is a disease of altered gene expression involving a complex array of
      epigenetic events, gene mutation, chromosome rearrangements and altered
      chromosome number. The coincidence of genotoxic events with the induction of
      cancer has fueled great interest in molecular/cytogenetic epidemiological studies
      aimed at linking polymorphisms in genes for DNA repair and carcinogen metabolism
      and biomarkers of DNA/chromosome damage with cancer risk. These studies are now
      being expanded to include the role of dietary factors that are known to be
      important in DNA metabolism and repair such as folic acid, vitamin B12 and zinc.
      The use of DNA damage biomarkers as a surrogate for cancer would greatly
      facilitate our capacity to identify the most important risk factors for cancer
      however these biomarkers need validation. The Nordic and Italian prospective
      cohort studies have confirmed that elevated rates of chromosome aberrations in
      lymphocytes are predictive of cancer risk and similar studies are now underway to
      validate other biomarkers such as the micronucleus assay which are more practical
      to apply in the larger population setting. Validation of these biomarkers
      requires a thorough understanding of the importance of methodological,
      demographic, environmental and dietary variables and the ongoing HUMN project is
      a good example how this can be achieved for the micronucleus assay. The capacity
      to study human populations has opened up new opportunities to define acceptable
      DNA damage rates and to establish recommended dietary allowances for genomic
      stability. Controlling DNA damage rate to its possible minimum is likely to have
      an important impact in preventing cancer and other DNA damage-related
      degenerative diseases including ageing.

PMID- 12505345
TI  - Current developments in food additive toxicology in the USA.
AB  - A recently published proposal (Fed. Reg. 66 (2001) 4706) for mandatory submission
      of information on all plant-derived bioengineered foods fed to humans or animals
      will be reviewed. Under this proposal, information such as data on identity,
      level and function of the introduced substance(s); an estimate of dietary
      exposure; allergenic potential of the protein; data relevant to other safety
      issues that may be associated with the substance; selection of a comparable food;
      historic uses of comparable food; composition and characteristics of
      bioengineered food versus those of the comparable food should be provided. In
      addition, characterization of the parent plant; construction of the
      transformation vector and introduced genetic material along with number of
      insertion sites and genes; data on the genetic material and any newly inserted
      genes for antibiotic resistance should be submitted with the notification. The
      Interagency Coordinating Committee for Validation of Alternative Methods (ICCVAM)
      was identified by the U.S. Congress as the organization to review and validate
      new alternative toxicological test methods for 14 U.S. government agencies.
      Validated and accepted alternative toxicity tests will be incorporated into
      toxicity testing recommendations for regulatory agencies.

PMID- 12505346
TI  - Safety assessment of genetically modified crops.
AB  - The development of genetically modified (GM) crops has prompted widespread debate
      regarding both human safety and environmental issues. Food crops produced by
      modern biotechnology using recombinant techniques usually differ from their
      conventional counterparts only in respect of one or a few desirable genes, as
      opposed to the use of traditional breeding methods which mix thousands of genes
      and require considerable efforts to select acceptable and robust hybrid
      offspring. The difficulties of applying traditional toxicological testing and
      risk assessment procedures to whole foods are discussed along with the evaluation
      strategies that are used for these new food products to ensure the safety of
      these products for the consumer.

PMID- 12505347
TI  - Substantial equivalence--an appropriate paradigm for the safety assessment of
      genetically modified foods?
AB  - Safety assessment of genetically modified food crops is based on the concept of
      substantial equivalence, developed by OECD and further elaborated by FAO/WHO. The
      concept embraces a comparative approach to identify possible differences between
      the genetically modified food and its traditional comparator, which is considered
      to be safe. The concept is not a safety assessment in itself, it identifies
      hazards but does not assess them. The outcome of the comparative exercise will
      further guide the safety assessment, which may include (immuno)toxicological and
      biochemical testing. Application of the concept of substantial equivalence may
      encounter practical difficulties: (i) the availability of near-isogenic parental
      lines to compare the genetically modified food with; (ii) limited availability of
      methods for the detection of (un)intended effects resulting from the genetic
      modification; and (iii) limited information on natural variations in levels of
      relevant crop constituents. In order to further improve the methodology for
      identification of unintended effects, new 'profiling' methods are recommended.
      Such methods will allow for the screening of potential changes in the modified
      host organism at different integration levels, i.e. at the genome level, during
      gene expression and protein translation, and at the level of cellular metabolism.

PMID- 12505348
TI  - Recent advances in the study of epigenetic effects induced by the phycotoxin
      okadaic acid.
AB  - Okadaic acid (OA) is a phycotoxin produced by dinoflagellates. It accumulates in
      the digestive tracts of shellfish causing diarrhetic shellfish poisoning (DSP) in
      consumers. OA is a tumour promoter, and an inhibitor of both protein phosphatases
      and protein synthesis. OA induces DNA adducts, suggesting it may be carcinogenic.
      Since the Ames test without S(9) was negative, but a mutagenesis test was
      positive in mammalian cells, the question as to whether its molecular mechanism
      is genotoxic or epigenetic became unavoidable. Therefore, experiments were
      performed to search for epigenetic effects, since evidence for DNA-adduct
      formation using the gamma-(32)P-ATP post-labelling method was not obtained. We
      found that OA is a potent inducer of lipid peroxidation in human intestinal cells
      (Caco-2) at low concentrations (0.75-7.5 ng/ml versus IC50 of 15 ng/ml) with
      increased rates of 8-OH-dG and m(5)dC formation causing CG to AT transversion
      mutations and gene deregulation, respectively. The transcription and translation
      of connexin 43-specific mRNA were inhibited, and 3H-uridine incorporation in RNA
      was concomitantly increased. Consequently gap junction intracellular
      communication (GJIC) was inhibited, making possible cellular anarchic
      proliferation. Higher OA concentrations also disorganized the cellular
      cytoskeleton, since both actin and tubulin formations were impaired. Our results
      suggest that OA may induce tumours via an epigenetic mechanism.

PMID- 12505349
TI  - Human intoxication by microcystins during renal dialysis treatment in Caruaru
      Brazil.
AB  - In February 1996, an outbreak of illness occurred at a hemodialysis clinic in
      Caruaru, Pernambuco State-Brazil. At this clinic 116 (89%) of 131 patients
      experienced visual disturbances, nausea, vomiting, and muscle weakness, following
      routine haemodialysis treatment. Subsequently, 100 patients developed acute liver
      failure. As of December 1996, 52 of the deaths could be attributed to a common
      syndrome now called 'Caruaru Syndrome'. Examination of previous years'
      phytoplankton counts showed that cyanobacteria were dominant in the water supply
      reservoir since 1990. Analyses of carbon and other resins from the clinic's water
      treatment system plus serum and liver tissue of patients led to the
      identification of two groups of hepatotoxic cyanotoxins: microcystins (cyclic
      heptapeptides) in all of these samples and cylindrospermopsin (alkaloid
      hepatotoxic) in the carbon and resins. Comparison of victims symptoms and
      pathology with animal studies on these two cyanotoxins, leads us to conclude that
      the major contributing factor to death of the dialysis patients was intravenous
      exposure to microcystins, specifically microcystin-YR, -LR and -AR. In 2000, a
      review of the Brazilian regulation for drinking water quality, promoted by
      Brazilian Health Ministry with collaboration of PAHO, incorporated cyanobacteria
      and cyanotoxins into this new regulation as parameters that must to be monitored
      for water quality control.

PMID- 12505350
TI  - Polymorphism of cytochrome P450 and xenobiotic toxicity.
AB  - The majority of human P450-dependent xenobiotic metabolism is carried out by
      polymorphic enzymes which can cause abolished, quantitatively or qualitatively
      altered or enhanced metabolism. The latter situation is due to stable
      duplication, multiduplication or amplification of active genes, most likely in
      response to dietary components that have resulted in a selection of alleles with
      multiple non-inducible genes. An updated list of variant CYP alleles is present
      at the Home Page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee
      (http://www.imm.ki.se/CYPalleles/). Several examples exist where subjects
      carrying certain alleles suffer from a lack of drug efficacy due to ultrarapid
      metabolism or, alternatively, adverse effects from the drug treatment due to the
      presence of defective alleles. Dosage requirements for several commonly used
      drugs that have a narrow therapeutic range can differ more than 20-fold dependent
      on the genotype or the enzyme expression status. By contrast, carcinogen
      metabolising cytochrome P450s are less polymorphic and no firm relationships have
      been established linking increased risk for cancer with any specific P450
      polymorphism. In the present overview recent aspects of cytochrome P450
      polymorphism and xenobiotic toxicity are discussed.

PMID- 12505351
TI  - Genetic polymorphisms of UDP-glucuronosyltransferases and their functional
      significance.
AB  - UDP-Glucuronosyltransferase (UGT), the microsomal enzyme responsible for
      glucuronidation reactions, exists as a superfamily of enzymes. Genetic
      polymorphism has been described for 6 of the 16 functional human UGT genes
      characterised to date, namely UGT 1A1, 1A6, 1A7, 2B4, 2B7 and 2B15. Since
      glucuronidation is an essential pathway for the elimination of a myriad of
      xenobiotics and endogenous compounds, genetic polymorphism of UGT is potentially
      of toxicological and physiological importance. However, functional significance
      has only been convincingly demonstrated for genetic polymorphism of UGT1A1. Apart
      from impaired bilirubin glucuronidation, the mutations responsible for Gilbert
      syndrome also affect the elimination of a limited number of xenobiotics. It has
      been proposed on the basis of altered catalytic activity of mutants of UGT 1A6,
      1A7 and 2B15 that genetic polymorphism of these forms may be of toxicological
      significance, but this is yet to be proven.

PMID- 12505352
TI  - The relationship between polymorphisms of xenobiotic metabolizing enzymes and
      susceptibility to cancer.
AB  - Although it is well established that highly penetrant genes explain less than 5%
      of all cancers, it is much less clear what proportion is attributable to low
      penetrant genes and their interactions with environmental exposures. It was
      possible to estimate indirectly the fraction of lung and bladder cancers
      attributable to known genetic polymorphisms, on the basis of an extensive review
      of the literature, and of the pooled analyses of approximately 15000 healthy
      subjects in three continents. The emerging picture is one of considerable
      homogeneity within ethnic group, and heterogeneity among ethnic groups. By
      combining relative risks and genotype frequencies we have computed theoretical
      attributable risks for lung and bladder cancers and the CYP1A1 Msp1, CYP1A1 Exon
      7, GSTM1 and NAT2*5 genotypes, among Caucasians and among Asians. Such
      attributable risks are probably overestimated, since: (a) they include the
      interaction with carcinogenic exposures, in the absence of which genetic
      polymorphisms per se are not effective; (b) they do not reflect the combination
      of different genotypes. However, our calculations suggest that attributable risks
      due to genetic susceptibility are much lower than those related to smoking or
      other environmental risk factors, and that Asians seem to carry higher risks than
      Caucasians. In addition, a theoretical approach to the problem of gene
      environment interactions at low levels of exposure is offered.

PMID- 12505353
TI  - Genomics and the prediction of xenobiotic toxicity.
AB  - The systematic identification and functional analysis of human genes is
      revolutionizing the study of disease processes and the development and rational
      use of drugs. It increasingly enables medicine to make reliable assessments of
      the individual risk to acquire a particular disease, raises the number and
      specificity of drug targets and explains interindividual variation of the
      effectiveness and toxicity of drugs. Mutant alleles at a single gene locus for
      more than 20 drug metabolizing enzymes are some of the best studied individual
      risk factors for adverse drug reactions and xenobiotic toxicity. Increasingly,
      genetic polymorphisms of transporter and receptor systems are also recognized as
      causing interindividual variation in drug response and drug toxicity. However,
      pharmacogenetic and toxicogenetic factors rarely act alone; they produce a
      phenotype in concert with other variant genes and with environmental factors.
      Environmental factors may affect gene expression in many ways. For instance,
      numerous drugs induce their own and the metabolism of other xenobiotics by
      interacting with nuclear receptors such as AhR, PPAR, PXR and CAR. Genomics is
      providing the information and technology to analyze these complex situations to
      obtain individual genotypic and gene expression information to assess the risk of
      toxicity.

PMID- 12505354
TI  - Separating potential source exposure from background exposure in subsistence
      populations in developing countries.
AB  - Risk assessment methods of developed countries have prescribed exposure
      assumptions for calculating health risks that are generally inappropriate for
      developing countries because of population, cultural, and social differences. For
      example, populations in developing countries are often subsistence users of
      natural resources with a more outdoor-oriented lifestyle. Assessments should thus
      measure specific dietary intake rates and contact rates with environmental media.
      Chemical analyses of food, environmental media, and any biomarkers of exposure
      should include a carefully matched reference population to distinguish between
      exposures due to naturally occurring metals in more mineralized areas and
      potential anthropogenic sources. Without a reference group, one might predict
      excess risk associated with the external source, even though exposure is due to
      background levels. For example, subsistence populations often have a simple diet
      with high ingestion rates of a few food types (e.g. 200 g/day wet weight of fish;
      500 g/day of rice). These foods can be naturally elevated in arsenic (fish and
      rice) and mercury (fish). Conservative risk assessments that extrapolate toxicity
      from high to low doses can predict elevated risks for these naturally occurring
      elements (e.g. greater than 1 in 10,000 cancer risk for arsenic). Whether the
      calculated risks are actually indicative of harm to subsistence populations
      should be considered in light of the beneficial properties of the diet and the
      lack of alternative food choices.

PMID- 12505355
TI  - History of the events leading to the formulation of the apoptosis concept.
AB  - Histological studies of ischaemic liver injury performed between 1962 and 1964
      distinguished two types of cell death: classical necrosis, and a process
      involving conversion of scattered cells into small round masses of cytoplasm that
      often contained specks of condensed nuclear chromatin. Enzyme histochemistry
      demonstrated rupture of lysosomes in the former, but preservation of lysosomes in
      the latter. Similar small round masses were also observed sparsely in normal
      liver. Electron microscopy showed that the small round bodies resulted from
      cellular condensation and budding, that they were bounded by membranes and
      contained intact organelles, and that they were phagocytosed and digested by
      resident tissue cells, including epithelial cells. In work done in association
      with Jeffrey Searle, the process was found to occur spontaneously in a variety of
      malignant tumours and to be enhanced in squamous cell carcinomas of skin
      responding to radiotherapy. During 1971-1972, I collaborated with Andrew Wyllie
      and Alastair Currie while on sabbatical leave in Scotland. The newly defined type
      of cell death was shown to be regulated by hormones in the adrenal cortex and in
      breast carcinomas. Further, review of published electron micrographs of the cell
      death known to play an essential role in normal development revealed the same
      morphological pattern. We proposed that this distinctive phenomenon subserves a
      general homoeostatic function and suggested it be called apoptosis.

PMID- 12505356
TI  - Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis.
AB  - Although toxicants may initiate cell damage or stress, the cellular proteins that
      are involved in control of cell cycle and apoptosis are the final arbiters of
      cell fate. The biochemical pathways that restrain cell cycle transition and/or
      induce cell death after stress are known as cell cycle checkpoints. These
      checkpoints maintain the fidelity of DNA replication, repair, and division.
      Herein, select cell cycle checkpoint signaling pathways will be discussed and how
      different components of these pathways are regulated by exogenous and endogenous
      agents, with focus on the p53 tumor suppressor signaling. The p53 protein is
      known to play a key role in growth arrest and apoptosis after cell stress,
      primarily through its ability to regulate the transcription of select downstream
      target genes in the cell. Further elucidation of the signaling pathways that
      control growth arrest and apoptosis will continue to provide insights to the
      complex cellular responses to environmental toxicants.

PMID- 12505357
TI  - Upregulation of FasL and apoptosis in thymic lymphomas in Atm knock-in mice.
AB  - Several members of the phosphatidylinositol 3-kinase family play key roles in
      recognising and responding to damage in DNA, induced by a variety of chemicals
      and other agents. One of these, ATM, the product of the gene mutated in the human
      genetic disorder ataxia-telangiectasia (A-T), recognises double strand breaks in
      DNA caused by ionizing radiation and radiomimetic chemicals. In order to study
      DNA damage recognition and the abnormalities of genome instability and cancer
      predisposition that occur in A-T patients, we generated a mouse model expressing
      a mutant form of Atm corresponding to a common human mutation. In this model, a 9
      nucleotide in-frame deletion was introduced into the Atm gene and has been
      designated Atm-Delta SRI. These animals had a longer lifespan than Atm gene
      disrupted mice (Atm(-/-)) and they developed less thymic lymphomas. A
      characteristic of the lymphomas appearing in Atm-Delta SRI mice was an increased
      rate of apoptosis compared to the corresponding tumours in Atm(-/-) mice.
      Increased expression of FasL in these tumours may account for the higher levels
      of apoptosis. These results demonstrate that expression of mutant Atm in mice
      gives rise to phenotypic differences compared to Atm(-/-) mice and has
      implications for heterogeneity described in the human syndrome.

PMID- 12505358
TI  - Role of mitochondria in toxic cell death.
AB  - Apoptosis is a highly regulated form of cell death distinguished by the
      activation of a family of cysteine-aspartate proteases (caspases) that cleave
      various proteins resulting in morphological and biochemical changes
      characteristic of this form of cell death. Abundant evidence supports a role for
      mitochondria in regulating apoptosis. Specifically, it seems that a number of
      death triggers target these organelles and stimulate, by an unknown mechanism,
      the release of several proteins, including cytochrome c. Once released into the
      cytosol, cytochrome c binds to its adaptor molecule, apoptotic protease
      activating factor-1, which oligomerizes and then activates pro-caspase-9. Caspase
      9 can signal downstream and activate pro-caspase-3 and -7. The release of
      cytochrome c can be influenced by different Bcl-2 family member proteins,
      including Bax, Bid, Bcl-2, and Bcl-X(L). Bax and Bid potentiate cytochrome c
      release, whereas Bcl-2 and Bcl-X(L) antagonize this event. Although toxicologists
      have traditionally associated cell death with necrosis, emerging evidence
      suggests that different types of environmental contaminants exert their toxicity,
      at least in part, by triggering apoptosis. The mechanism responsible for
      eliciting the pro-apoptotic effect of a given chemical is often unknown, although
      in many instances mitochondria appear to be key participants. Here, we provide an
      overview of our current understanding of the role of apoptosis in toxicant
      induced cell death, using dioxin, organotin compounds, dithiocarbamates, as well
      as the chemotherapeutic agent etoposide, as specific examples.

PMID- 12505359
TI  - Issues at the interface between ecology and toxicology.
AB  - Although facing many similar problems, there are differences between ecology and
      toxicology in the nature and aspect of some issues. Scientific challenges relate
      to the fundamentals of toxicology and ecology. For dose and response, the metrics
      of dose and response, methods for extrapolation from lab to field, generally
      accepted definitions of adverse effects (including definitions for health and
      categorization of detectable versus adverse responses), and classification of
      mixture toxicity and effects are current areas of interest. Policy challenges are
      more related to the use of science in public policy and regulations; essentially,
      where and how science is used in decision-making. As both toxicology and ecology
      are employed in actions on environmental matters, interactions between policy
      decision-making and scientific knowledge generation are also examined.

PMID- 12505360
TI  - Mining in the Alligator Rivers Region, northern Australia: assessing potential
      and actual effects on ecosystem and human health.
AB  - This paper presents an overview of issues related to surface water contamination
      arising from uranium mining activities in the Alligator Rivers Region (ARR) of
      northern Australia, and a program of research and monitoring that must assess the
      potential and actual effects on ecosystem and human health. The program of
      assessing effects on aquatic ecosystems involves a four-tiered approach including
      the derivation of local water quality guideline trigger values, direct toxicity
      assessment of mine waters prior to their release, creekside or in situ monitoring
      for early warning of adverse effects during mine water release, and longer-term
      monitoring of macroinvertebrate and fish communities. Bioaccumulation in aquatic
      biota is also assessed, and is an issue of importance not only to ecosystem
      health, but also to the health of local Aboriginal people. The aquatic animals
      they consume represent potential sources of radiological dose, and as a result, a
      major component of the program to assess potential effects on human health is the
      prediction of doses to Aboriginal people living downstream of mining activities.
      Acknowledging the assumptions and uncertainties, the calculation of concentration
      factors for local aquatic (and other) food sources allows the prediction of
      potential radiological exposure to people following hypothetical mine water
      releases. The approaches described form the basis of best-practice protocols that
      are relevant at both regional and national levels.

PMID- 12505361
TI  - Biomarkers in toxicology versus ecological risk assessment.
AB  - Toxicity testing of drugs, pesticides, and hazardous compounds has evolved into a
      battery of standardized tests conducted in a range of surrogate test organisms.
      The toxicity of these xenobiotics in terms of their LD(50) and LC(50) (Dose or
      concentration lethal to 50% of the test population), ED(50) and EC(50) (Dose or
      concentration producing a specified response in 50% of the test population), MATC
      (Maximum acceptable toxicant concentration), LOEL (Lowest observable effects
      level), LOEC (Lowest observable effects concentration), NOEL (No observable
      effects level) or NOEC (No observable effects concentration) is extrapolated to
      humans and wildlife. Historical failures in the risk assessment process have been
      largely due to over reliance on regulatory toxicology and an 'assembly line'
      mentality to toxicology. The importance of toxicokinetics, receptor studies and
      biomarkers are reviewed, firstly, with reference to toxicological incidences in
      drug development programmes, and secondly, with reference to improved
      environmental risk assessment of pesticides and other contaminants. Ecological
      risk assessments also require multidisciplinary skills to study the entry,
      distribution, and biological effect and fate of chemicals to fully characterise
      and understand the potential adverse implications of contamination. Optimum
      integration of chemical measurements and biomarker responses is a challenge that
      will lead to an improved understanding of adverse effects and their significance
      in both human and ecological risk assessment.

PMID- 12505362
TI  - Sodium monofluoroacetate (1080) risk assessment and risk communication.
AB  - Sodium monofluoroacetate (1080) is a vertebrate pesticide widely used for possum
      control in New Zealand. Fluoroacetate is also a toxic component of poisonous
      plants found in Australia, South Africa, South America, and India. Because of its
      importance and effectiveness in pest control and the highly toxic nature of this
      compound, its acute sub-lethal and target organ toxicity have been extensively
      studied. In relation to its use as a pesticide its environmental fate,
      persistence, non-target impacts and general toxicology have been and continue to
      be extensively studied. Toxic baits must be prepared and used with extreme care,
      otherwise humans, livestock, and non-target wildlife will be put at risk. The
      high risk of secondary poisoning of dogs is a cause for concern. 1080 acts by
      interfering with cellular energy production. Possums die from heart failure,
      usually within 6-18 h of eating baits. Long-term exposure to sub-lethal doses can
      have harmful effects and strict safety precautions are enforced to protect
      contractors and workers in the bait manufacturing industry. Considerable care is
      taken when using 1080 to ensure that the risks of using it are outweighed by the
      ecological benefits achieved from its use. When its use is controversial, risk
      communicators must take care not to trivialise the toxicity of the compound. The
      benefits of 1080 use in conservation, pest control, and disease control should be
      weighed up alongside the risks of using 1080 and other techniques for pest
      control.

PMID- 12505363
TI  - Toxicology tests with aquatic animals need to consider the trophic transfer of
      metals.
AB  - Water quality criteria for metals have largely been based on toxicity tests in
      which organisms are exposed to dissolved metals, often at concentrations that
      exceed by several orders of magnitude those which are found even in contaminated
      waters; these tests assume that ecological impacts can be extrapolated from acute
      toxicity assessments. We have shown that when marine copepods are exposed to
      metals (Ag, Cd, Hg, Se, Zn) through their diet the reproductive capacity
      decreases by up to 75% because fewer eggs are produced and the hatching success
      of the eggs which are produced is diminished. These sublethal effects occur at
      metal concentrations that are 2-3 orders of magnitude below acutely toxic
      concentrations. Metals accumulated in copepods by trophic transfer deposit in
      internal tissues, and only modest increases above background levels can depress
      reproductive capability. Metals accumulated from the dissolved phase deposit
      primarily on external surfaces, where they have negligible effects at
      environmentally realistic concentrations. Toxicity tests must consider the
      bioaccumulation of metals from dietary exposure in order to account for sublethal
      effects at metal concentrations that are comparable to those in contaminated
      waters.

PMID- 12505364
TI  - Identifying toxic mechanisms using DNA microarrays: evidence that an experimental
      inhibitor of cell adhesion molecule expression signals through the aryl
      hydrocarbon nuclear receptor.
AB  - Microarray analysis of gene expression has become a powerful approach for
      exploring the biological effects of drugs and other chemicals. In toxicology
      research, gene expression profiling may help identify hazards by comparing
      results for an experimental compound with a database, and establish mechanistic
      hypotheses through examination of discrete gene changes. Here we examine the
      hepatic effects of a thienopyridine inhibitor of NF-kappa B-mediated expression
      of cellular adhesion proteins. In a 3-day toxicity study in Sprague-Dawley rats,
      A-277249 induced hypertrophy of the liver and elevated serum levels of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase
      (ALP). To investigate mechanism, microarray analysis was done on RNA from livers
      of A-277249-treated rats. Gene expression profiles from A-277249 were compared
      with a database of profiles from fifteen known hepatotoxins. Agglomerative
      hierarchical cluster analysis showed A-277249 to have a profile most similar to
      the aromatic hydrocarbons Aroclor 1254 and 3-methylcholanthrene (3MC), two known
      activators of the aryl hydrocarbon nuclear receptor (AhR). Several genes
      regulated by the AhR, including cytochrome P450 1A1, were upregulated by A
      277249. In addition, several genes involved in apoptosis and cell cycle were
      differentially expressed consistent with cell turnover, hypertrophy and
      hyperplasia observed by histology. Results from this study indicate that A-277249
      hepatic toxicity is mediated by the AhR either directly or through effects on NF
      kappa B, and demonstrate the utility of microarray analysis for the rapid
      identification of toxic hazards for new chemical entities.

PMID- 12505365
TI  - Custom cDNA microarrays; technologies and applications.
AB  - Technologies designed to characterise genes and their products on a discovery
      scale are now having an impact on many areas of biology, including toxicology. A
      number of platforms exist which measure changes in expression of potentially
      thousands of genes simultaneously. These approaches, when applied to toxicology,
      are termed 'toxicogenomics' and promise to greatly facilitate mechanism-based
      research on toxicant action with the longer term possibility of assisting in the
      identification of potential toxicity issues earlier in the development of new
      pharmaceutical, agrochemical and chemical products. An example of such a platform
      developed in our laboratory is ToxBlot II, a custom microarray containing cDNAs
      representing 12564 human genes chosen on the basis of their potential relevance
      to a broad range of toxicities. ToxBlot II can assist in characterising many
      outcomes including processes as diverse as immune system response, receptor
      biology, signal transduction, protein modification, membrane transport, growth
      and development, metabolism, oxidative stress and regulation of the cell
      cytoskeleton. Furthermore, ToxBlot II allows the simultaneous expression
      profiling of genes representing entire cellular pathways, facilitating a very
      detailed investigation of potential mechanisms of toxicity. Our laboratory is
      applying this and other custom microarrays to many areas of toxicology, including
      endocrine disruption, receptor biology, stress response and the effect of
      toxicants on immune function. Such approaches can be particularly valuable when
      used in conjunction with 'functional genomics' such as transgenic or knockout
      models.

PMID- 12505366
TI  - Genomic interrogation of mechanism(s) underlying cellular responses to toxicants.
AB  - Assessment of the impact of xenobiotic exposure on human health and disease
      progression is complex. Knowledge of mode(s) of action, including mechanism(s)
      contributing to toxicity and disease progression, is valuable for evaluating
      compounds. Toxicogenomics, the subdiscipline which merges genomics with
      toxicology, holds the promise to contributing significantly toward the goal of
      elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global
      gene expression profiling, revolutionized by microarray technology and a crucial
      aspect of a toxicogenomic study, allows measuring transcriptional modulation of
      thousands of genes following exposure to a xenobiotic. We use our results from
      previous studies on compounds representing two different classes of xenobiotics
      (barbiturate and peroxisome proliferator) to discuss the application of
      computational approaches for analyzing microarray data to elucidate mechanism(s)
      underlying cellular responses to toxicants. In particular, our laboratory
      demonstrated that chemical-specific patterns of gene expression can be revealed
      using cDNA microarrays. Transcript profiling provides discrimination between
      classes of toxicants, as well as, genome-wide insight into mechanism(s) of
      toxicity and disease progression. Ultimately, the expectation is that novel
      approaches for predicting xenobiotic toxicity in humans will emerge from such
      information.

PMID- 12505367
TI  - The regulation of herbal medicines in Australia.
AB  - Complementary medicines, including herbal medicines in Australia are regulated
      under therapeutics goods legislation. Based on risk, Australia has developed a
      two tiered approach to the regulation of therapeutic goods. Listed medicines are
      considered to be of lower risk than Registered medicines. Most, but not all,
      complementary medicines are Listed medicines. Managing the risk associated with
      therapeutic goods, including complementary medicines, is exerted through the
      processes of licensing of manufacturers; pre-market assessment of products; and
      post-market regulatory activity. Herbal medicines may be associated with low or
      high risk depending on the toxicity of ingredients, proposed dosage,
      appropriateness of the indications and claims for self-diagnosis and management
      and the potential for adverse reactions. Registered medicines are individually
      evaluated for safety, quality and efficacy before they are released onto the
      market. Listed medicines are individually assessed by the Therapeutic Goods
      Administration for compliance with legislation, they are not evaluated before
      release. They may only be formulated from ingredients that have undergone pre
      market evaluation for safety and quality and are considered low risk. Listed
      complementary medicines may only carry indications and claims for the symptomatic
      relief of non-serious conditions, health maintenance, health enhancement and risk
      reduction. An important feature of risk management in Australia is that early
      market access for low risk complementary medicines is supported by appropriate
      post-market regulatory activity.

PMID- 12505368
TI  - Clinical and laboratory investigations in herbal poisonings.
AB  - Herbs have been used world-wide, particularly in Chinese society, for thousands
      of years. Conceptually, herbs are usually considered to be non-toxic by the
      general public due to their natural origin. However, the consumption of herbs is
      well-known to be capable of producing prominent adverse health effects. Due to
      increased morbidity and mortality, poisonings associated with the use of herbs
      have raised universal attention in the last few years. In daily practice, herbs
      are dispensed by health professionals, quacks and other non-medical
      professionals, such as witch doctors, for either therapeutic or tonic purposes.
      Upon exposure, the clinical toxicity may vary from mild to severe and may even be
      life-threatening. In the clinical setting, the difficulties involved in handling
      the poisonings associated with the use of herbs can be categorized as follows:
      (1) difficulties in the identification of the proprietary substances and active
      ingredients; (2) problems with characterizing the kinetic pattern and
      toxicological effects; and (3) the uncertainty of the treatment. A systematic
      approach, including both clinical and laboratory investigations, is required in
      handling cases of herbal poisonings. Critical factors for the clinical
      investigation are the observation and documentation of clinical symptoms and
      signs, as well as the collection of information concerning prescription,
      packaging, herbal residues, herbal samples, amount consumed and the processing
      methods of the herbs. A geographically and culturally oriented data bank of
      analytical systems should be created to assist in the future laboratory diagnosis
      of herbal poisonings.

PMID- 12505369
TI  - Renal interstitial fibrosis and urothelial carcinoma associated with the use of a
      Chinese herb (Aristolochia fangchi).
AB  - A new renal disease called 'Chinese-herb nephropathy' (CHN) has been reported to
      occur in women who have ingested slimming pills containing powdered extracts of
      the Chinese herb Stephania tetrandra (ST). Moderate to end-stage renal disease
      developed, requiring renal replacement therapy by dialysis or transplantation.
      Phytochemical analyses of the pills revealed the presence of aristolochic acids
      (AA) instead of tetrandrine, suggesting the substitution of ST (Han fang ji) by
      Aristolochia fangchi containing nephrotoxic and carcinogenic AA. A typical
      histological feature of CHN is a progressive interstitial fibrosis leading to a
      severe atrophy of the proximal tubules, as documented by the urinary excretion
      rates of markers of tubular integrity (reduction of neutral endopeptidase
      enzymuria and high levels of microproteinurias). Removal of the native kidneys
      and ureters in end-stage CHN patients provided a high prevalence of urothelial
      carcinoma (46%). Tissue samples contained AA-related DNA adducts, which are not
      only specific markers of prior exposure to AA but are also directly involved in
      tumorigenesis. Exposure to Aristolochia species (spp.) is associated with the
      development of renal interstitial fibrosis (CHN) and urothelial cancer in humans.
      Health professionals should be aware that in traditional Chinese medicine,
      Aristolochia spp. are considered interchangeable with certain other herbal
      ingredients and are also sometimes mistaken for ST, Akebia, Asarum, Clematis spp.
      and Cocculus spp. in herbal remedies.

PMID- 12505370
TI  - Regulation and quality control of herbal drugs in Korea.
AB  - Korea has a great diversity in resources of medicinal plants. The traditional
      herbal medicines and their preparations have been widely used in Korea as well as
      in China and Japan for thousands of years. One of the characteristics of Korean
      herbal medicine preparations is that all the herbal medicines are incorporated
      into an extractor at the same time and extracted with boiling water during the
      decoction process. In this process, a variety of interactions between the active
      components of several herbal medicines may occur. This is the main reason why
      quality control of oriental herbal drug is more difficult than that of western
      herbal drug. In this paper, we would like to present an overview of the
      characteristics of regulation and quality control of herbal medicines in Korea.

PMID- 12505371
TI  - Mercuric chloride induces apoptosis via a mitochondrial-dependent pathway in
      human leukemia cells.
AB  - Mercurial compounds modulate immunologic functions by inducing cytotoxicity.
      Although mercury chloride (HgCl(2)) is known to induce apoptosis in various
      immune system cells, the mechanism of the induction of apoptosis is poorly
      understood. In this study, we examined the activation of caspase-3, an important
      cysteine aspartic protease, during HgCl(2)-induced apoptosis in a human leukemia
      cell line (HL-60 cells). Both DNA fragmentation, a characteristic of apoptotic
      cells, and proteolysis of poly(ADP-ribose) polymerase (PARP), a substrate of
      caspase-3, occurred at 6 h after HgCl(2) treatment in HL-60 cells. These results
      suggest that the activation of caspase-3 was involved in HgCl(2)-induced
      apoptosis. The release of cytochrome c (Cyt c) from mitochondria into the
      cytosol, which is an initiator of the activation of caspase cascades, was also
      observed in HgCl(2)-treated HL-60 cells. Moreover, the release of Cyt c from
      mitochondria was observed in HgCl(2)-treated mitochondria isolated from mice
      liver, and this was followed by mitochondrial permeability transition (PT). The
      PT was inhibited by cyclosporin A (CsA), a potent inhibitor of PT. CsA also
      suppressed the occurrence of DNA fragmentation induced by HgCl(2) treatment in HL
      60 cells. Taken together, these findings indicate that HgCl(2) is a potent
      inducer of apoptosis via Cyt c release from the mitochondria in HL-60 cells.

PMID- 12505372
TI  - The flame retardants tetrabromobisphenol A and tetrabromobisphenol A
      bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25)
      in murine splenocytes.
AB  - Polybrominated flame retardants (PBF) are frequently used additives in
      electronical equipment. They are ubiquitous environmental contaminants which
      bioaccumulate with several health effects for humans and the environment. This
      study investigated immunotoxic effects of the PBF tetrabromobisphenol A (TBBP A),
      tetrabromobisphenol A-bisallylether (TBBP A-AE), tetrabromobisphenol A-bis-(2,3
      dibromopropyl-ether) (TBBP A-PE), decabromodiphenylether (DBDE), and 2,4,6
      tribromophenol (TBP) in vitro. The structurally related polychlorinated aromatic
      hydrocarbon 3,4,3',4'-tetrachlorobiphenyl (PCB77) and dioxins mediate their
      immunotoxicity via the Ah-receptor gene complex. A highly relevant function of
      the Ah receptor, the induction of CYP 1A1 in hepatocytes of C57BL/6 mice by the
      established inducers 3-methylcholanthrene (MC) and PCB77 was compared to the
      effect of PBF by measurement of ethoxyresorufin-o-deethylase (EROD) activity. The
      PBF did not show any induction of CYP 1A1, while EROD activity of hepatocytes
      exposed to MC and PCB77 was induced 10.8- and 8.7-fold, respectively. To
      investigate immunotoxic effects of the flame retardants, splenocytes of C57BL/6
      mice were incubated with subtoxic doses of the flame retardants and PCB77 and
      activated by concanavalin A (Con A). The flame retardants TBBP A and TBBP A-AE
      significantly inhibited the expression of interleukin-2 receptor alpha chain
      (CD25) in contrast to TBBP A-PE, DBDE, TBP, and PCB77 as shown by
      immunohistochemistry and quantitative analysis by laser scanning cytometry. None
      of the substances had any effect on the Con A-induced production of cytokines.
      Hence, TBBP A and TBBP A-AE may act as immunotoxic compounds by specifically
      inhibiting the expression of CD25.

PMID- 12505373
TI  - Effect of prolonged exposure to low antigen concentration for sensitization.
AB  - The local lymph node assay (LLNA) is an assay in mice to identify potential
      allergens. Compounds that do not induce a stimulation index (SI)>or=3 are not
      considered sensitizers. Of the chemicals that do, the SI of 3 is used as a
      benchmark, and indicates the sensitizing potency of a chemical. Compared to the
      exposure duration of the LLNA (3 days), real life exposure often lasts for months
      or years. We therefore investigated whether prolonged exposure to sensitizers at
      concentrations that do not induce a SI>or=3 in the LLNA, were able to surpass
      this threshold. Mice were treated for 2 months at 7-day intervals with a range of
      concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ),
      2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both
      proliferative activity and cytokine production were established at day 60.
      Neither BENZ nor TMTD showed a significant increase in the proliferation rate
      compared to vehicle controls. Only DNCB at concentrations originally above the
      EC(3) a significant increase in proliferation was seen after prolonged exposure.
      No significant effect on IFN-gamma and IL-4 production was observed for all three
      compounds compared. These findings indicate that for classification of
      sensitizers the shorter exposure period employed in the standard LLNA is
      sufficient, and longer periods of exposure have no bearing on this
      classification.

PMID- 12505374
TI  - Intracellular survival of Staphylococcus aureus due to alteration of cellular
      activity in arsenic and lead intoxicated mature Swiss albino mice.
AB  - The role of heavy metals like arsenic (As) and lead (Pb) as environmental
      toxicants is established. However, the exact mechanism of their effect on
      immunocompetent cell activity is not well known. Staphylococcus aureus is a
      virulent pathogen that has the ability to cause a variety of potentially life
      threatening infections. The objective of our study was to demonstrate in an
      experimental mouse model of bacteremic S. aureus infection, bacterial clearance
      from blood and spleen in arsenic, lead treated and control group of mice.
      Bacterial density was measured in blood and spleen after 0, 24, 48 and 72 h post
      infection. Our findings show a significant increase in bacterial load in blood
      (P<0.025 for arsenic and P<0.01 for lead) and delayed bacterial clearance by
      spleen in both arsenic (P<0.05) and lead (P<0.025) treated groups as compared to
      control, thus highlighting an immuno-compromised state following heavy metal
      exposure. To further elucidate immunomodulatory effects of both arsenic and lead,
      cell function studies were performed on splenic macrophages (M(phi)) isolated
      from lead and arsenic treated as well as control group of mice. Our findings show
      a decrease in cell adhesion property (P<0.005) of splenic M(phi)s from 2.9925+/
      0.053 in control to 1.395+/-0.106 in arsenic and 0.8835+/-0.0106 in lead treated
      mice at 60 min. Morphologic alteration of the splenic M(phi)s showed an increase
      (As: P<0.05, Pb: P<0.0005) in both arsenic (6.876+/-0.3287%) and lead (16.55+/
      1.051%) treated mice to control (2.649+/-1.238%) which may be responsible for the
      formers' reduced functional status. The chemotactic index, a measure of
      chemotactic migration of the macrophages toward immune serum, was 16.43+/-1.007
      in control cell and was reduced (P<0.0005) to 4.19+/-0.393 in arsenic and 2.92+/
      0.649 in lead treated mice at 60 min. These altered cell functions could probably
      explain the intracellular survival of S. aureus but such a causal relationship
      awaits further detailed examination.

PMID- 12505375
TI  - Effect of inhaled industrial chemicals on systemic and local immune response.
AB  - Using immunotoxic functional tests, namely IgM response to sheep red blood cells
      (SRBCs) and interferon-gamma (IFN-gamma) production, this study simultaneously
      evaluated the effects of inhaled chloroform (10, 20, and 50 ppm), carbon
      tetrachloride (100, 200, and 300 ppm), 1,1-dichloroethylene (5, 10, and 15 ppm),
      and styrene (100, 200, and 300 ppm) on the systemic (spleen) and local (lung
      associated lymph nodes) immune response. At least one concentration of all the
      chemicals studied provoked a statistically significant increase in IgM response
      in the lymph nodes compared with the controls, as expressed by the number of
      plaque-forming cells (PFCs), whereas only the highest concentration of 1,1
      dichloroethylene provoked an increase in the number of PFCs statistically
      different from the controls in the case of the spleens. The release of IFN-gamma
      in the lymph node cell cultures of the exposed mice exceeded that of the controls
      by more than 600%, whereas the release of IFN-gamma in the spleen cell cultures
      of the exposed mice was moderately different from the controls. It would appear
      from these results that the lung-associated lymph nodes are sensitive targets for
      chemical inhalation and that the results of systemic tests in the spleen may not
      mirror local immune response dysfunction. For risk assessment of inhaled
      chemicals, it is therefore important to take the local immunotoxic effects into
      consideration, in particular immunostimulation which may be involved in the rise
      in allergic diseases in industrialised countries.

PMID- 12505376
TI  - Development of sensitisation or tolerance following repeated OVA inhalation in
      BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant.
AB  - Anthropogenically induced exposures may, due to their adjuvant effect, promote
      development of sensitisation to commonly occurring aeroallergens. No generally
      accepted model exists for determination of adjuvant effect of airborne
      substances. Therefore, BALB/cJ mice were exposed for 10 consecutive days with
      ovalbumin (OVA) solution, 25 mg/l-10 g/l (0.0025-1%) for 20 min/day, with and
      without the Al(OH)(3) adjuvant (0.5%). Four days after the last aerosol exposure,
      no OVA specific IgE and only low IgG1 were produced. Subsequent parenteral OVA
      administration showed that the 10 g/l solution induced full tolerance of the IgE
      response, whereas only partial tolerance was apparent with 25 mg/l OVA. The
      Al(OH)(3) adjuvant counteracted development of tolerance that was fully prevented
      at the 25 mg/l OVA concentration. Development of IgG1 was increased in a
      concentration-dependent manner with 500 mg/l-10 g/l OVA. No increase occurred at
      the 25 mg/l level, but addition of Al(OH)(3) increased IgG1 production to the
      same level as the higher OVA concentrations. Concentrations from 1.25 mg/l to 10
      g/l OVA were studied with ten exposures followed by once-weekly aerosol exposure
      for uptil 6 weeks. In the range from 1.25 mg/l to 10 g/l, IgE production was time
      and concentration-dependent. Both the IgE and IgG1 production were markedly
      promoted by Al(OH)(3). However, with aerosol exposures, the IgE antibody
      productions were not sufficient to increase the level of inflammatory cells in
      broncho-alveolar lavage fluid. Overall, this study showed that airborne Al(OH)(3)
      was able to counteract tolerance and increase specific IgE and IgG1 production.

PMID- 12505377
TI  - Effects of the mycotoxin ochratoxin A and some of its metabolites on the human
      cell line THP-1.
AB  - The immunomodulatory effects of ochratoxin A (OTA) and some of its metabolites on
      the human monocyte/macrophage line THP-1 are described. Metabolic activity, cell
      proliferation, cell membrane integrity, cell differentiation, phagocytic
      behaviour, nitrogen oxide synthesis and cell surface markers were largely
      suppressed by these mycotoxins at concentrations between 10 and 1000 ng/ml, in
      individual cases already at 1 ng/ml. After analysis of a crude toxin, a substance
      designated RE2 could be isolated besides OTA, which was identified as ochratoxin
      C (OTC). The latter showed a stronger suppressive effect on most functions
      studied than all other metabolites of OTA. Because of the immunomodulatory
      effects of OTA and OTC, more attention should be paid to their immunopathogenic
      importance in addition to their known cytotoxic and genotoxic effects. The
      occurrence and importance of the mycotoxin OTC should be more closely examined in
      this context.

PMID- 12505378
TI  - Effects of 17a-ethinylestradiol on the expression of three estrogen-responsive
      genes and cellular ultrastructure of liver and testes in male zebrafish.
AB  - In order to monitor the influence of estrogenic compounds on the reproductive
      physiology of fish, molecular markers for zebrafish vitellogenin, estrogen
      receptor and ZP2 were developed. For this purpose, sequence information about the
      zebrafish estrogen receptor and vitellogenin had to be obtained. By means of RT
      PCR, a sequence fragment of the zebrafish estrogen receptor alpha was cloned and
      sequenced. Continuous cDNAs of two zebrafish vitellogenin-like gene products
      (zfvg1 and zfvg3) were constructed by the help of expressed sequence tags of
      zebrafish and completely sequenced. The sequences of the estrogen receptor and of
      the vitellogenins showed significant similarities to corresponding cDNAs of other
      fish species. Expression of these gene products was measured following exposure
      to 17alpha-ethinylestradiol and compared with histological endpoints. RT-PCR was
      used as a semiquantitative technique to record gene expression in adult male
      zebrafish, which were exposed to 17alpha-ethinylestradiol in time-and dose
      response experiments. As for time-dependent expression, all hepatic genes
      investigated were expressed at considerable amounts from 24 h after onset of
      exposure to 50 ng/l 17alpha-ethinylestradiol to the end of experiment (17 days).
      In testes, expression of the estrogen receptor- as well as ZP2-mRNA remained
      unchanged for the entire experiment, except for the individuals exposed for 17
      days, which displayed elevated expression levels of ZP2. In the dose-response
      experiment, male zebrafish were exposed to 17alpha-ethinylestradiol in
      concentrations from 0.25-85 ng/l for 4 and 21 days. LOECs for vitellogenin as
      well as estrogen receptor alpha expression were found to be 2.5 ng/l already
      after 4 d of exposure. Extension of the exposure time to 21 days resulted in
      enhanced transcription of vitellogenin-mRNAs at 2.5 ng/l 17alpha
      ethinylestradiol, whereas the detection limit could not be lowered. In contrast,
      in testes no induction of both ZP2 as well as estrogen receptor expression was
      detected at any concentration tested. To examine estrogen-caused alterations at
      the ultrastructural level, liver and testes of males exposed to 25 ng/l 17alpha
      ethinylestradiol were analysed. Male livers responded with a feminisation
      reflected by the proliferation of rough endoplasmatic reticulum and Golgi
      apparatus typical of female hepatocytes during vitellogenesis. However, in testes
      no signs of feminisation were detectable; rather, destructive phenomena like
      phagocytosis of sperm cells by Sertoli cells were observed. Thus, in sexually
      differentiated males no reorganisation of the gonadal tissue towards an ovary
      could be definitely detected at any level investigated.

PMID- 12505379
TI  - Multivariate analyses of invertebrate community responses to a C12-15 AE-3S
      anionic surfactant in stream mesocosms.
AB  - The ecological effects of a C(12-15)AE-3S linear alkylethoxysulfate anionic
      surfactant on aquatic organisms were studied in stream mesocosms. Analyses of the
      experimental data have yielded multiple population-level no-observed effect
      concentrations (NOECs) but did not provide a measure of community-level response
      to surfactant exposure. In the present study, the invertebrate data from the
      mesocosm study were further examined for community-level effects using
      multivariate techniques. Two multivariate statistical methods were selected as
      representative of recommended methods and used to analyze invertebrate abundance.
      One method was similarity analysis using the Bray-Curtis index, and the second
      method was the canonical ordination technique principal response curves recently
      developed for analysis of mesocosm data. Both sets of techniques detected
      statistically significant changes in invertebrate community structure following
      surfactant exposure. Ordinations constructed from Bray-Curtis similarity matrices
      provided clearer two-dimensional representations of these changes than
      ordinations from redundancy analysis. Re-displaying treatment and temporal
      effects on community structure on separate axes as response curves provided a
      clearer method for interpreting community response to surfactant exposure. Both
      approaches detected treatment effects in low and high abundance taxa. The highest
      rank abundance taxa in the pretreatment streams contributed very little to the
      differences observed between the control and treated streams. The same set of
      taxa was identified as the dominant drivers for structural differences between
      control and treated communities despite underlying mathematical differences in
      these two methods. Invertebrate community-level NOECs estimated from these
      different multivariate methods (2.5-5.0 mg/l) were comparable and these NOECs
      were similar to invertebrate population NOECs determined for this surfactant.

PMID- 12505380
TI  - Effects of sewage effluent and ethynyl oestradiol upon molecular markers of
      oestrogenic exposure, maturation and reproductive success in the sand goby
      (Pomatoschistus minutus, Pallas).
AB  - Male fish in several UK estuaries are known to be exposed to oestrogenic
      contamination, and whilst a limited number of studies have shown that exposure to
      oestrogens can reduce the reproductive success of fish, the impact of
      environmentally relevant exposures is less clear. The aim of this study was,
      therefore, to investigate the effects of exposure to environmentally realistic
      concentrations of a sewage effluent and the synthetic oestrogen 17alpha-ethynyl
      oestradiol (EE(2)) upon the reproductive success of a marine fish. Sand goby
      (Pomatoschistus minutus) were exposed for 7 months to EE(2) or a sewage effluent
      containing known xeno-oestrogens (alkylphenol polyethoxylates) and bred using
      within treatment crosses. Nominal exposure concentrations were 6 ng l(-1) EE(2),
      0.3 or 0.03% v/v sewage effluent. At the end of the breeding trials, expression
      of hepatic zona radiata protein (Zrp) and vitellogenin (Vtg) mRNA were determined
      using two recently developed cDNA probes. Exposure to 6 ng l(-1) EE(2) induced
      Zrp and Vtg mRNA expression in male and female sand goby, impaired male
      maturation and reproductive behaviour, reduced female fecundity and reduced egg
      fertility. As a consequence, fertile egg production of the EE(2)-exposed
      population was reduced by 90%. Exposure to sewage effluent (0.3% v/v) increased
      adult mortality and female Zrp and Vtg mRNA expression, but did not induce male
      vitellogenesis. Exposure to EE(2) and 0.3% v/v sewage effluent impaired
      development of the male urogenital papilla. Fish exposed to 0.03% v/v sewage
      effluent produced more fertile eggs than those exposed to 0.3% effluent, or those
      receiving no effluent. It is concluded that male vitellogenesis in an
      oestrogenically exposed population may be accompanied by reduced reproductive
      success, but that it may not be indicative of altered reproductive output in a
      population exposed to an industrial sewage effluent.

PMID- 12505381
TI  - Insights into the mechanisms of copper tolerance of a population of black-banded
      rainbowfish (Melanotaenia nigrans) (Richardson) exposed to mine leachate, using
      64/67Cu.
AB  - This study investigates the mechanisms of copper tolerance of a population of
      black-banded rainbowfish (Melanotaenia nigrans) (Richardson). The population has
      been exposed to elevated copper concentrations for over 40 years, due to leachate
      from the Rum Jungle uranium/copper mine. At the time of collection the 96 h
      EC(50) of exposed [E] fish was 8.3 times higher than that of reference [R] fish.
      The bioconcentration of 64/67Cu in fish was used to investigate the mechanism of
      copper tolerance in E fish. Both E and R fish were exposed to low (L(Cu), 30
      microg Cu l(-1)) and elevated (E(Cu), 300 microg Cu l(-1)) copper concentrations
      for 24 and 48 h, respectively. Radioactivity was measured at seven or eight time
      points in four tissue sections: head (including gills, heart and brain), internal
      organs (including gastrointestinal tract, liver, kidneys and gonads), muscle and
      whole body. One-compartment bioconcentration models were fit to data and compared
      using an F-test. Copper concentrations in all tissue sections were significantly
      (P<0.05) less (up to 50%) in E fish compared with the respective tissue sections
      of R fish when exposed to both L(Cu) and E(Cu). The exception was copper
      accumulation in the internal organs, which was not significantly different
      between E and R fish exposed to E(Cu). The mechanism of copper tolerance was
      concluded to be reduced copper uptake in the gills, rather than increased binding
      or elimination. Allozyme electrophoresis was performed to determine if genetic
      selection had occurred in the E fish population. Allozyme frequencies at the AAT
      1 and GPI-1 loci were significantly (P<0.05) different between E and R fish.
      Heterozygosity was reduced in E fish compared with that of R fish. Collectively
      these results suggest that genetic selection may have occurred in the E fish
      population. Consequently, the selection of allozymes less sensitive to copper may
      be another mechanism of copper tolerance of E fish. This is the first study on
      the mechanisms of copper tolerance in a wild fish population that has been
      exposed to elevated copper concentrations. These findings aid the understanding
      of metal tolerance in fish and emphasise the importance of sample selection and
      its implication for toxicity testing.

PMID- 12505382
TI  - When adapted to high zinc concentrations the periphytic green alga Stigeoclonium
      tenue produces high amounts of novel phytochelatin-related peptides.
AB  - Two ecotypes of the green alga Stigeoclonium tenue Kutz. coming from polluted or
      unpolluted freshwaters and showing various Zn-tolerance were compared for their
      production of non-proteinaceous thiols in response to Zn. In short-term (17 h)
      exposures to 15 microM Zn they did not reveal any significant difference in
      levels of glutathione, phytochelatins and some unknown thiols. However, after
      prolonged metal exposure (48 h) the Zn-tolerant S. tenue (T) isolated from Zn
      polluted mining water, produced at the expense of GSH besides phytochelatins
      (PC(2)-PC(4)) much higher amounts of novel, phytochelatin-related peptides. After
      a 6-week exposure to 30 microM Zn, phytochelatins (approximately 6 micromol SH
      per g D.W.) and the novel thiol peptides (approximately 31 micromol SH per g
      D.W.), only in the surviving Zn-tolerant alga, were produced. HPLC analysis
      suggested that the novel peptides (P1-P3) differ from each other by one gammaGlu
      Cys unit. ESI/MS analysis of the purified, most abundant peptides P2 and P3, of
      m/z values 643 and 875, respectively, suggested that they contain one cysteine
      residue more than PC(2) and PC(3). A 22-fold higher concentration of these
      peptides in Zn-tolerant S. tenue (T) than in Zn-sensitive S. tenue (S) was also
      observed in response to Pb exposure. Biosynthesis of the large amounts of the
      novel thiol peptides, which contain more SH-groups than phytochelatins, detected
      in the Zn-tolerant organism after long Zn exposure, and lack of such a response
      in the Zn-sensitive ecotype S. tenue (S), isolated from unpolluted water, suggest
      that they are essential in the adaptation of S. tenue (T) to increased heavy
      metal concentrations.

PMID- 12505383
TI  - Tissue differences, dose-response relationship and persistence of DNA adducts in
      blue mussels (Mytilus edulis L) exposed to benzo[a]pyrene.
AB  - Baltic Sea blue mussels (Mytilus edulis) were experimentally exposed to the
      genotoxic model substance benzo[a]pyrene (B[a]P) to study DNA adduct formation.
      The specific aims were (a). to examine where in the mussels the DNA adducts were
      formed, in gills or digestive gland; (b). to study the dose-response relationship
      between B[a]P exposure and DNA adduct formation; and (c). to examine the
      persistence of the formed adducts. A Scope for growth (SFG) study was also run to
      compare physiological responses of the mussels with the degree of DNA adduct
      formation. In an initial dose-response experiment, the mussels were exposed to 0,
      5, 50, and 100 microg/l of tritium labelled B[a]P under semi-static conditions
      for 4 days, and thereafter the bioaccumulation of B[a]P and DNA adduct formation
      in different tissues was determined using liquid scintillation counting and 32P
      postlabelling analysis, respectively. In a following exposure-depuration
      experiment, mussels were exposed to 17 microg/l of radiolabelled B[a]P under semi
      static conditions for 6 days. B[a]P accumulation and DNA adduct formation were
      determined during the exposure, and B[a]P elimination and persistence of DNA
      adducts were studied during 28 days of depuration in uncontaminated water. The
      results revealed large tissue differences in DNA adduct formation. DNA adduct
      levels were not elevated in the digestive gland of the mussels at any exposure
      concentration (0-100 microg/l), even though the highest B[a]P tissue
      concentrations were found in the digestive gland (1.0+/-0.1 mg B[a]P/g tissue dry
      wt at 100 microg/l, mean+/-SE, n=12). DNA adducts were on the other hand formed
      in the gills, with the highest levels found in mussels exposed to 50 and 100
      microg B[a]P/l, and a dose dependent increase in adduct levels (from 1.6 to 5.9
      nmol adducts/mol nucleotides) from 0 to 50 microg B[a]P/l. In gills, DNA adduct
      levels increased with time during the 6-day exposure period in the exposure
      depuration experiment, and then persisted for at least 2 weeks after exposure
      cessation while B[a]P tissue levels exhibited a rapid decrease (half-life of 8
      days). No significant differences were observed in SFG between the control and
      exposed groups. Since DNA adducts exhibited a relatively high persistence in
      gills compared to B[a]P tissue concentrations, they seem to be a more integrated
      measure of genotoxic exposure than only chemical analysis of the contaminant
      bioaccumulation. The results also suggest that if using analysis of DNA adducts
      in M. edulis for monitoring purposes, analysis of gills in addition to the more
      commonly used digestive gland should be taken into consideration.

PMID- 12505384
TI  - New vaccines for a new world.

PMID- 12505386
TI  - Structure and function in the exercising horse--will veterinarians miss out yet
      again?

PMID- 12505388
TI  - Porcine circovirus and postweaning multisystemic wasting syndrome--possible new
      links.

PMID- 12505389
TI  - Is avian influenza research meeting the needs of the poultry veterinarian?

PMID- 12505390
TI  - Radiation therapy for the treatment of tumours in small companion animals.
AB  - Radiation is becoming widely available to treat tumours in veterinary patients.
      Orthovoltage machines capable of delivering low energy external beam radiation
      are less versatile than linear accelerators and cobalt-60 machines that deliver
      megavoltage radiation. In addition, electron beam capabilities that are available
      with some linear accelerators allow more targeted treatment in smaller patients.
      Acute effects of radiation are to be expected, but in nearly all cases such side
      effects resolve without limiting protocols. In contrast, late effects of
      radiation are dose limiting and are more likely with higher doses per treatment
      fraction. Protocols that use smaller doses per fraction have a lower risk of late
      effects thereby allowing higher total doses to be delivered which leads to higher
      tumour control rates. It is possible to provide long-term tumour control in cats
      and dogs using radiation therapy, particularly for mast cell tumours, soft tissue
      sarcomas, oral tumours and brain tumours in dogs and soft tissue sarcomas and
      skin tumours in cats. Individualization of treatments for tumours based on tumour
      staging and proliferative fraction should be considered, rather than making
      blanket assumptions about the behaviour of histologically determined tumour
      types.

PMID- 12505392
TI  - Vaccination: a management tool in veterinary medicine.
AB  - Conventional vaccines have been used for some 200 years, primarily to control
      infectious diseases. It is envisaged that such vaccines will continue to be used
      and new ones developed using conventional technology. However, in addition to
      conventional vaccines, novel approaches using biotechnology are already in use
      and many more are in various stages of development. These novel vaccines are not
      only being used to control infectious diseases, but also to improve productivity
      of livestock by modulating hormones, for gender selection, as well as in
      controlling ectoparasites. The recent developments in vaccination technology in
      all of these areas are described.

PMID- 12505393
TI  - Recent developments in avian influenza research: epidemiology and
      immunoprophylaxis.
AB  - Influenza A viruses have been isolated from humans, from several other mammalian
      species and a wide variety of avian species, among which, wild aquatic birds
      represent the natural hosts of influenza viruses. The majority of the possible
      combinations of the 15 haemagglutinin (HA) and nine neuraminidase (NA) subtypes
      recognized have been identified in isolates from domestic and wild birds.
      Infection of birds can cause a wide range of clinical signs, which may vary
      according to the host, the virus strain, the host's immune status, the presence
      of any secondary exacerbating microorganisms and environmental factors. Most
      infections are inapparent, especially in waterfowl and other wild birds. In
      contrast, infections caused by viruses of H5 and H7 subtypes can be responsible
      for devastating epidemics in poultry. Despite the warnings to the poultry
      industry about these viruses, in 1997 an avian H5N1 influenza virus was directly
      transmitted from birds to humans in Hong Kong and resulted in 18 confirmed
      infections, thus strengthening the pandemic threat posed by avian influenza (AI).
      Indeed, reassortant viruses, harbouring a combination of avian and human viral
      genomes, have been responsible for major pandemics of human influenza. These
      considerations warrant the need to continue and broaden efforts in the
      surveillance of AI. Control programmes have varied from no intervention, as in
      the case of the occurrence of low pathogenic (LP) AI (LPAI) viruses, to extreme,
      expensive total quarantine-slaughter programmes carried out to eradicate highly
      pathogenic (HP) AI (HPAI) viruses. The adoption of a vaccination policy, targeted
      either to control or to prevent infection in poultry, is generally banned or
      discouraged. Nevertheless, the need to boost eradication efforts in order to
      limit further spread of infection and avoid heavy economic losses, and advances
      in modern vaccine technologies, have prompted a re-evaluation of the potential
      use of vaccination in poultry as an additional tool in comprehensive disease
      control strategies. This review presents a synthesis of the most recent research
      on AI that has contributed to a better understanding of the ecology of the virus
      and to the development of safe and efficacious vaccines for poultry.

PMID- 12505394
TI  - Osteological and morphometric observations on intervertebral joints in the canine
      pre-diaphragmatic thoracic spine (Th1-Th9).
AB  - The incidence of facet aplasia was investigated in three groups of pure-bred
      dogs. We examined large breeds (Rough Collies, Doberman Pinschers, Rottweilers,
      Bernese Mountain Dogs, German Shepherd Dogs), chondrodystrophic breeds
      (Dachshunds, Pekinese dogs), and small breeds (Yorkshire Terriers, Maltese dogs).
      Uni- or bilateral aplasia of zygapophyseal (facet) joints was exclusively found
      in juvenile and adult small dogs, in which the incidence of aplasia ranged from
      between 26% (Th1) and 63% (Th8). There was no evidence that aplasia of
      zygapophyseal joints increases the risk of developing intervertebral disc disease
      or deformative spondylosis in small breeds. By applying the findings of previous
      empirical studies on intervertebral disc geometry and its biomechanical behaviour
      on the present morphometric results, there was an indication that the
      intervertebral disc may well compensate for the functional loss of aplastic
      zygapophyseal joints in small dogs. Biomechanical factors and their potential
      role as inducing agents of facet aplasia in the pre-diaphragmatic thoracic spine
      are also discussed.

PMID- 12505395
TI  - Overview of horse body composition and muscle architecture: implications for
      performance.
AB  - Locomotion requires skeletal muscle to sustain and generate force. A muscle's
      force potential is proportional to its weight. Since the larger the muscle the
      larger its potential power output, a better understanding of the proportion of
      skeletal muscle a horse possesses may lead to a better understanding of horse
      performance. Several techniques exist to assess body composition, which include
      dual energy X-ray absorption, underwater (hydrostatic) weighing, derivation from
      total body water, bio-electric impedance, air displacement, body condition
      scoring, cadaver dissection and ultrasound. The relevance of each method to the
      equine industry will be discussed as will the practical information that the
      existing horse body composition studies have provided. Attention will be given to
      the data regarding the implications of body composition on the performance horse.
      The limited number of studies discussing different varieties of muscle
      architectures and the functional importance of these muscles will also be
      addressed. These body composition data may provide a better understanding of
      important issues in horse care that can lead to more optimal horse care
      techniques and a healthier and safer environment for horses.

PMID- 12505396
TI  - 24-hour Holter-monitoring in the perianaesthetic period in dogs premedicated with
      dexmedetomidine.
AB  - Baseline and perianaesthetic 24-hour Holter recordings were carried out in six
      healthy beagles. After dexmedetomidine premedication anaesthesia was induced with
      propofol and maintained with propofol infusion or isoflurane for one hour.
      Dexmedetomidine alone was used as control. The recordings were analysed for
      ventricular premature complexes (VPC), atrioventricular (AV) blocks and mean
      heart rate/hour (HR). In most recordings, no ventricular arrhythmias were
      detected, the maximum frequency being two VPCs/24 h. VPCs were not seen during
      anaesthesia or during the recovery period. The development of second-degree AV
      blocks varied from dog to dog. Most of the heart blocks were seen during the
      premedication period when bradycardia was most prominent. During the subsequent
      night, HR was similar between treatments and did not differ from that seen on the
      baseline recordings. In beagles treated with dexmedetomidine alone or combined
      with propofol or propofol/isoflurane, ventricular arrhythmias were not detected
      more frequently than those reported in healthy non-anaesthetised dogs.

PMID- 12505397
TI  - The influence of the site of application on the behavioural responses of lambs to
      tail docking by rubber ring.

PMID- 12505398
TI  - Effect of tris-buffer, egg yolk and glycerol on canine semen freezing.

PMID- 12505399
TI  - Double in situ hybridization for simultaneous detection and differentiation of
      porcine circovirus 1 and 2 in pigs with postweaning multisystemic wasting
      syndrome.
AB  - Double in situ hybridization using a digoxigenin-labelled porcine circovirus 1
      (PCV1) and biotinylated PCV2 probe, was developed for the simultaneous detection
      and differentiation of PCV1 and PCV2 in formalin-fixed, paraffin-embedded tissues
      from pigs with postweaning multisystemic wasting syndrome. The combination of an
      alkaline phosphatase conjugated antidigoxigenin system with alkaline phosphatase
      conjugated streptavidin-biotin system allowed identification of PCV1 and/or PCV2.
      No evidence of cross-reaction was observed. Positive cells exhibited a red or
      dark brown reaction product for PCV1 and PCV2, respectively. Both PCV DNAs were
      observed mainly in the cytoplasm but occasionally in the nucleus. Co-localization
      of hybridization signal for both PCV1 and PCV2 was present in macrophages and
      multinucleated giant cells of the lymph node and spleen. This double-labelling
      technique for the differentiation between PCV1 and PCV2 is suitable for
      pathogenesis studies and diagnostic applications.

PMID- 12505400
TI  - Composition and milk cell characteristics in quarter milk fractions of dairy cows
      with low cell count.
AB  - Variation in milk composition and milk polymorphonuclear neutrophil leukocyte
      (PMN) characteristics and functions among quarter milk fractions were
      investigated in order to evaluate the optimal fraction for the determination of
      local immune response. Five fractions were classified during milking: foremilk
      (I), cisternal milk (II), main milk (III), strippings (IV) and residual milk (V).
      Somatic cell count (SCC), fat, protein, lactose, sodium, potassium, chloride,
      polymorphonuclear leukocyte necrosis, apoptosis and oxidative burst were analysed
      in each fraction. The logSCC and fat concentration were highest in residual milk
      (P < 0.05), whereas protein and lactose concentration were highest in the
      earliest fractions (I, II, III) (P < 0.05). Polymorphonuclear neutrophil
      leukocyte necrosis was lowest in strippings and residual milk (P < 0.05), and PMN
      apoptosis was lowest in residual milk (P < 0.001). The highest percentage of PMN
      with oxidative burst was found in residual milk (P < 0.05), and was associated
      with the highest mean fluorescence intensity (MFI) (P < 0.05). In conclusion,
      late fractions have more PMN and more active PMN. Nevertheless, it is suggested
      that each fraction is appropriate in the study of local immune response of the
      mammary gland, however the fraction used in the study has to be specified.

PMID- 12505401
TI  - Effects of haemolysis, lipaemia, bilirubinaemia and fibrinogen on protein
      electropherogram of canine samples analysed by capillary zone electrophoresis.
AB  - The possible interference of haemolysis, lipaemia, bilirubinaemia and fibrinogen
      on capillary zone electrophoresis of canine samples were studied. Solutions of
      haemoglobin, lipid and bilirubin were prepared and mixed with serum aliquots to
      make up samples containing different concentrations of the putative interferent
      substance. In addition, samples of serum and plasma were assayed to assess the
      influence of fibrinogen. Haemolysis and lipids produced a change in
      electropherogram morphology giving an interference peak located in the beta-2
      region when haemoglobin was increased, and in the alpha-2 region when lipids were
      increased. A rise in concentration of these interferents caused an increase in
      the beta and alpha-2 fractions respectively, and a decrease in the other
      fractions. Bilirubin did not alter morphology but gave an increase in the albumin
      and alpha-1 and a decrease in the alpha-2 and beta-2 fractions. No differences
      were found between serum and plasma samples, and fibrinogen did not produce any
      additional peak.

PMID- 12505402
TI  - Quantification of thrombopoietic activity in bone marrow aspirates of dogs.
AB  - The aims of the study were to investigate possible influences of different
      numbers of counted fields on slides, and different slides on the counting of
      platelet precursors, and to establish guidelines for bone marrow examination in
      dogs. The study was based on bone marrow slides of 131 healthy dogs. The slides
      were prepared by a squash technique. On each slide the number of thrombopoietic
      cells at different levels of maturation were counted in all fragment-containing
      fields. The results of a variance component model revealed no influence of
      different slides, in contrast to a high variance related to different fields.
      Between 20 and 25 low power fields (100x magnification) had to be examined to
      achieve an imprecision of 20%. An imprecision of 10% required the counting of 100
      fields. The lowest thrombopoietic activity was seen in the bone marrow of dogs
      aged one to six years. The total number of platelet percursors per field was
      significantly higher in adult female (10.4 +/- 2.67) than in male dogs (7.84 +/-
      2.04, P = 0.0008) as was the number of megakaryocytes. We recommend assessment of
      thrombopoiesis on the basis of 20-25 fragment-containing low power fields and
      that age- and sex-related differences should be considered.

PMID- 12505403
TI  - Influence of diet on the shedding of Candida glabrata by experimentally infected
      preweaned calves.
AB  - The influence of three diets, comprising dam's milk (DM) from the same farm,
      commercial milk replacer with (CMRL) or without 3.2% lactose (CMR), on the
      duration and intensity of Candida glabrata shedding in the faeces of preweaned
      calves following experimental oral infection was examined. Shedding of other
      potential enteric pathogens was also monitored. The duration and intensity of C.
      glabrata shedding in DM-fed calves were reduced significantly compared with the
      calves fed the two diets based on milk replacers. Consequently, feeding calves
      with DM might disrupt the infective cycle, resulting in the yeast's elimination
      from a farm. In the CMR and CMRL groups, the periods of intensive shedding of C.
      glabrata and rotavirus overlapped but no diarrhoea was associated with the
      shedding of either microorganism. There was no evidence that lactose diminished
      colonization in vivo.

PMID- 12505405
TI  - Effect of experimental therapeutic ultrasound on the distal antebrachial growth
      plates in one-month-old rabbits.
AB  - The effect of therapeutic ultrasound (US) on the growth plates of growing bone
      was determined through fluorescence labelling and histopathological evaluation in
      one-month-old rabbits. Mean growth rates and mean heights of the growth plates of
      the US exposed radius vs. control radius, and US exposed ulna vs. control ulna
      showed no statistically significant differences at all intensities and time
      intervals. Mean growth rates and heights of the growth plates of the US exposed
      radius for 0.2 W/cm(2) (SATA) US vs. 0.5 W/cm(2) US showed the same type of
      pattern compared to those of the control radius for 0.2 W/cm(2)vs. 0.5 W/cm(2) at
      days 10, 15 and 20. Similar results were also found for the ulna. Effects of 0.5
      W/cm(2) US on the mean growth rates and mean heights of the growth plates were
      superior to those of 0.2 W/cm(2) US at day 10. The results at day 10 were
      reversed for the same comparisons at days 15 and 20. No cavitation effect of US
      was observed on growth plate cells. There was no evidence of partial or complete
      premature closure of the growth plates or of angular deformity of the carpal
      region.

PMID- 12505406
TI  - An updated equine influenza vaccine and an equine influenza-herpesvirus
      combination vaccine containing an immunostim adjuvant provoke equal antibody
      levels in young foals throughout the primary vaccination course.

PMID- 12505407
TI  - Effect of postural change on lumbar epidural pressure in cattle.

PMID- 12505408
TI  - Dexamethasone increases serum leptin concentration in dogs.

PMID- 12505418
TI  - Neonatal viral infection decreases neuronal progenitors and impairs adult
      neurogenesis in the hippocampus.
AB  - While adult neurogenesis has been demonstrated in the hippocampal dentate gyrus
      of several mammalian species, including humans, the impact of viral infections
      has not been well studied. To examine this question we used a model in which
      neonatal rats are infected with lymphocytic choriomeningitis virus (LCMV) leading
      to a gradual loss of dentate granule cells (DGCs), which becomes fully evident in
      adulthood. Stereological cell counts performed 8 months after infection revealed
      that the loss of mature DGCs was accompanied by an 84.2% reduction in
      proliferation of DGCs as measured by BrdU uptake. Moreover, there was a severe
      loss of Mash1-labeled neuronal progenitor cells (87 and 83% decrease in the
      granule cell layer and hilus, respectively). Thus, neurogenesis is impaired in
      this model of chronic DGC loss, perhaps due to a virus-induced impoverishment of
      DGC neuronal progenitors. The LCMV model could be exploited to examine
      pathophysiological mechanisms of neurodegeneration and to test pharmacological
      strategies aimed at increasing neurogenesis or rescuing multipotent progenitors.

PMID- 12505417
TI  - Pathways leading to apoptotic neurodegeneration following trauma to the
      developing rat brain.
AB  - Trauma triggers diffuse apoptotic neurodegeneration in the developing rat brain.
      To explore the pathogenesis of this phenomenon we investigated the involvement of
      three possible mechanisms: death receptor activation, activation of the intrinsic
      apoptotic pathway by cytochrome c release into the cytoplasm, and changes in
      trophic support provided by endogenous neurotrophins. We detected a decrease in
      the expression of bcl-2 and bcl-x(L), two antiapoptotic proteins that decrease
      mitochondrial membrane permeability, an increase in cytochrome c immunoreactivity
      in the cytosolic fraction, and an activation of caspase-9 in brain regions which
      show apoptotic neurodegeneration following percussion brain trauma in 7-day-old
      rats. Increase in the expression of the death receptor Fas was revealed by RT-PCR
      analysis, Western blotting, and immunohistochemistry, as was activation of
      caspase-8 in cortex and thalamus. Apoptotic neurodegeneration was accompanied by
      an increase in the expression of BDNF and NT-3 in vulnerable brain regions. The
      pancaspase inhibitor z-VAD.FMK ameliorated apoptotic neurodegeneration with a
      therapeutic time window of up to 8 h after trauma. These findings suggest
      involvement of intrinsic and extrinsic apoptotic pathways in neurodegeneration
      following trauma to the developing rat brain. Upregulation of neurotrophin
      expression may represent an endogenous mechanism that limits this apoptotic
      process.

PMID- 12505419
TI  - Beta-amyloid-induced inflammation and cholinergic hypofunction in the rat brain
      in vivo: involvement of the p38MAPK pathway.
AB  - Injection into the nucleus basalis of the rat of preaggregated Abeta(1-42)
      produced a congophylic deposit and microglial and astrocyte activation and
      infiltration and caused a strong inflammatory reaction characterized by IL-1beta
      production, increased inducible cyclooxygenase (COX-2), and inducible nitric
      oxide synthase (iNOS) expression. Many phospho-p38MAPK-positive cells were
      observed around the deposit at 7 days after Abeta injection. Phospho-p38MAPK
      colocalized with activated microglial cells, but not astrocytes. The inflammatory
      reaction was accompanied by cholinergic hypofunction. We investigated the
      protective effect of the selective COX-2 inhibitor rofecoxib in attenuating the
      inflammatory response and neurodegeneration evoked by Abeta(1-42). Rofecoxib (3
      mg/kg/day, 7 days) reduced microglia and astrocyte activation, iNOS induction,
      and p38MAPK activation to control levels. Cholinergic hypofunction was also
      significantly attenuated by treatment with rofecoxib. We show here for the first
      time in vivo the pivotal role played by the p38MAPK microglial signal
      transduction pathway in the inflammatory response to the Abeta(1-42) deposit.

PMID- 12505420
TI  - Adenovirus-mediated Bcl-X(L) expression using a neuron-specific synapsin-1
      promoter protects against disseminated neuronal injury and brain infarction
      following focal cerebral ischemia in mice.
AB  - The effects of an adenovirus-mediated Bcl-X(L) expression, driven by a neuron
      specific human synapsin-1 promoter, on the degree of injury, were examined after
      transient focal ischemia in mice. Therefore, injections of vehicle, of an
      adenoviral E1-deleted control vector (Ad-dE1), or a Bcl-X(L) vector (Ad-Syn-Bcl
      X(L)) were stereotactically made in the striatum. Seven days later, focal
      ischemia was induced either by 30 min or 2 h of intraluminal thread occlusion. In
      line with previous data, 30 min of middle cerebral artery (MCA) occlusion
      reproducibly resulted in disseminated neuronal injury of the striatum, as
      revealed by cresyl violet and TUNEL 3 days after ischemia. The degree of cell
      injury was significantly reduced in Ad-Syn-Bcl-X(L) treated as compared with Ad
      dE1 and vehicle-treated animals. On the other hand, 2 h of MCA occlusion produced
      reproducible infarcts both in vehicle and Ad-dE1 treated animals 24 h after
      ischemia. The infarct area at the level of the striatum was significantly
      decreased by Ad-Syn-Bcl-X(L) treatment. The present data demonstrate that an
      adenoviral Bcl-X(L) expression with a neuron-specific synapsin-1 promoter
      provides a powerful tool, which not only diminishes disseminated neuronal injury,
      but also protects against tissue infarction.

PMID- 12505421
TI  - Niemann-Pick disease type C yields possible clue for why cerebellar neurons do
      not form neurofibrillary tangles.
AB  - It is unknown why cerebellar neurons resist neurofibrillary tangle (NFT)
      formation. In Niemann-Pick disease Type C (NPC), NFT-mediated neurodegeneration
      occurs throughout brain, but the cerebellum degenerates conspicuously without
      NFT. To understand why, we have studied markers of NFT pathogenesis in cerebellum
      from 17 NPC cases, all having abundant NFT in forebrain. Remarkably, we found
      that NPC cerebella display several early markers of NFT formation, i.e.,
      hyperphosphorylated tau and an array of cell cycle regulators, suggesting that
      cerebellar neurons in NPC undergo similar modifications as other neurons that
      develop NFT. However, cerebellar neurons are deficient in tau, the building block
      of NFT, and this may be one reason for their inability to form NFT. Even without
      NFT, cerebellar neurodegeneration may be triggered by the inappropriate
      activation of the cell cycle cdc2 kinase, and the npc-1 murine model provides an
      opportunity to test this hypothesis.

PMID- 12505422
TI  - Activation of GABA(A) receptors by guanidinoacetate: a novel pathophysiological
      mechanism.
AB  - Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessively
      inherited disorder of creatine biosynthesis. The disease occurs in early life
      with developmental delay or arrest and several neurological symptoms, e.g.,
      seizures and dyskinesia. Both the deficiency of high-energy phosphates in neurons
      and the neurotoxic action of the accumulated metabolite guanidinoacetate (GAA)
      are candidate mechanisms for the pathophysiology of this disease. To examine a
      potential role of GAA accumulation, we analyzed the electrophysiological
      responses of neurons induced by GAA application in primary culture and acute
      murine brain slices. GAA evoked picrotoxin- and bicuculline-sensitive GABA(A)
      receptor-mediated chloride currents with an EC(50) of 167 microM in cortical
      neurons. Pathophysiologically relevant GAA concentrations hyperpolarized globus
      pallidus neurons and reduced their spontaneous spike frequency with an EC(50) of
      15.1 microM. Furthermore, GAA acted as a partial agonist at heterologously
      expressed GABA(A) but not GABA(B) receptors. The interaction of GAA with neuronal
      GABA(A) receptors represents a candidate mechanism explaining neurological
      dysfunction in GAMT deficiency.

PMID- 12505423
TI  - Peripheral inflammatory response in Alzheimer's disease and multiinfarct
      dementia.
AB  - Whether peripheral inflammatory molecules can be considered markers of dementia
      is still an open issue. We have investigated the presence of circulating
      cytokines and the ability of blood cells to release them in response to an
      inflammatory stimulus in patients with different types of dementia and in age
      matched controls. A significant increase in circulating interleukin-1beta in
      moderate Alzheimer and in multiinfarct (145 and 224 times control concentration,
      respectively) dementia and in circulating tumor necrosis factor-alpha
      concentration in multiinfarct dementia patient group (156%) were found. Tumor
      necrosis factor-alpha and interleukin-6 released from blood cells after exposure
      to lipopolysaccharide were significantly reduced in moderate Alzheimer (60%, both
      cytokines) and multiinfarct patients (71 and 50%, respectively), while
      interleukin-10 was decreased only in multiinfarct patients (61%). The results
      show that patients with Alzheimer disease or multiinfarct dementia have an
      upregulation of circulating cytokines and a downregulation of cytokines released
      by blood cells.

PMID- 12505424
TI  - Molecular targeting of Alzheimer's amyloid plaques for contrast-enhanced magnetic
      resonance imaging.
AB  - Smart molecular probes for both diagnostic and therapeutic purposes are expected
      to provide significant advances in clinical medicine and biomedical research. We
      describe such a probe that targets beta-amyloid plaques of Alzheimer's disease
      and is detectable by magnetic resonance imaging (MRI) because of contrast
      imparted by gadolinium labeling. Three properties essential for contrast
      enhancement of beta-amyloid plaques on MRI exist in this smart molecular probe,
      putrescine-gadolinium-amyloid-beta peptide: (1) transport across the blood-brain
      barrier following intravenous injection conferred by the polyamine moiety, (2)
      binding to plaques with molecular specificity by putrescine-amyloid-beta, and (3)
      magnetic resonance imaging contrast by gadolinium. MRI was performed on ex vivo
      tissue specimens at 7 T at a spatial resolution approximating plaque size (62.5
      microm(3)), in order to prove the concept that the probe, when administered
      intravenously, can selectively enhance plaques. The plaque-to-background tissue
      contrast-to-noise ratio, which was precisely correlated with histologically
      stained plaques, was enhanced more than nine-fold in regions of cortex and
      hippocampus following intravenous administration of this probe in AD transgenic
      mice. Continuing engineering efforts to improve spatial resolution are underway
      in MRI, which may enable in vivo imaging at the resolution of individual plaques
      with this or similar contrast probes. This could enable early diagnosis and also
      provide a direct measure of the efficacy of anti-amyloid therapies currently
      being developed.

PMID- 12505425
TI  - In vitro studies of Flemish, Dutch, and wild-type beta-amyloid provide evidence
      for two-staged neurotoxicity.
AB  - Mutations in the beta-amyloid (Abeta) sequence of the amyloid precursor protein
      gene (APP) present with variable disease phenotypes. While patients with the
      Dutch APP mutation (E693Q) have predominantly hemorrhagic strokes, Flemish APP
      (A692G) patients develop both strokes and Alzheimer's disease (AD). To determine
      whether these diverse clinical and pathological presentations are due to mutant
      Abeta or APP, we studied the effect of Flemish, Dutch, and wild-type Abeta/APP on
      phosphorylation of specific tau epitopes observed in AD. No effect was observed
      in differentiated SH-SY5Y cells either stably expressing APP or treated with
      synthetic Abeta(12-42). However, we did observe a paradoxical temporal difference
      in the neurotoxic potential of mutant and wild-type Abeta. While long 24-h
      incubation at physiological levels of Abeta (2 microM) showed a higher amount of
      apoptosis for Dutch Abeta, a short 2-h incubation showed elevated apoptosis for
      Flemish and wild-type Abeta. The altered aggregating properties of Abeta, with
      Dutch Abeta aggregating faster and Flemish Abeta slower than wild type,
      elucidated a discrete two-phase Abeta neurotoxicity. We propose here that, at
      least in vitro, Abeta might be neurotoxic in an initial phase due to its soluble
      oligomeric or other early toxic Abeta intermediate(s), which is perhaps distinct
      from the late neurotoxicity incurred by aggregated larger assemblies of Abeta.

PMID- 12505426
TI  - Caspase-9 activation and caspase cleavage of tau in the Alzheimer's disease
      brain.
AB  - Accumulating evidence supports a role for the activation of proteolytic enzymes,
      caspases, in the Alzheimer's disease (AD) brain. Neurons committed to apoptosis
      may do so through a mitochondrial pathway employing caspase-9 or through an
      alternative, receptor-mediated pathway involving caspase-8. Considering the role
      of mitochondrial dysfunction in AD, we examined the possible activation of
      caspase-9 in the AD brain using an antibody that recognizes the active fragments
      of caspase-9, but not the full-length proform of the enzyme. In vivo
      immunohistochemical analysis demonstrated little caspase-9 activation in the
      majority of hippocampal brain sections from control brains. However, labeling of
      neurons as well as dystrophic neurites within plaque regions was observed in all
      AD hippocampal brain sections examined. In addition, active caspase-9 was
      colocalized with active caspase-8 and the accumulation of caspase-3-cleavage
      products of fodrin. The activation of caspase-9 was also observed in neurons
      positive for oxidative damage to DNA/RNA. A quantitative analysis indicates that
      as the number of neurons containing neurofibrillary tangles (NFTs) increases, the
      extent of caspase-9 activation decreases, supporting the idea that caspase-9
      activation may precede NFT formation. In addition, a site-directed caspase
      cleavage antibody was designed to the amino-terminal caspase-3 consensus cleavage
      site located in tau, and shown to be an effective marker for caspase-cleaved
      fragments of tau in vitro. Analysis with this antibody using age-matched control
      or AD brain sections demonstrated no staining in control brains while widespread
      labeling of NFTs, neuropil threads, and dystrophic neurites was observed in AD
      sections. Taken together, these results demonstrate the activation of caspases
      and cleavage of tau in the AD brain, events which may precede and lead to the
      formation of NFTs.

PMID- 12505428
TI  - Oxidative stress as a possible mode of action for arsenic carcinogenesis.
AB  - Many modes of action for arsenic carcinogenesis have been proposed, but few
      theories have a substantial mass of supporting data. Three stronger theories of
      arsenic carcinogenesis are production of chromosomal abnormalities, promotion of
      carcinogenesis and oxidative stress. This article presents the oxidative stress
      theory along with some supporting experimental data. In the area of which arsenic
      species is causually active, recent data have suggested that trivalent methylated
      arsenic metabolites, particularly monomethylarsonous acid (MMA(III)) and
      dimethylarsinous acid (DMA(III)), have a great deal of biological activity. Some
      evidence now indicates that these trivalent, methylated, and relatively less
      ionizable arsenic metabolites may be unusually capable of interacting with
      cellular targets such as proteins and even DNA. Thus for inorganic arsenic,
      oxidative methylation followed by reduction to trivalency may be a activation,
      rather than a detoxification pathway. This would be particularly true for
      arsenate. In forming toxic and carcinogenic arsenic species, reduction from the
      pentavalent state to the trivalent state may be as or more important than
      methylation of arsenic.

PMID- 12505429
TI  - Long-term arsenic exposure and ischemic heart disease in arseniasis-hyperendemic
      villages in Taiwan.
AB  - The association between long-term arsenic exposure and peripheral vascular
      disease has been well documented in our previous epidemiologic studies. The
      purpose of this study was to evaluate whether long-term arsenic exposure could be
      associated with ischemic heart disease (IHD). A total of 462 subjects living in
      the blackfoot disease-hyperendemic villages along the southwestern coast of
      Taiwan and characterized by long-term arsenic exposure from drinking artesian
      well water was studied. The subjects were recruited from an epidemiologic cohort
      who participated in a health examination. IHD was diagnosed by coding the resting
      electrocardiograms with the Minnesota code. History of arsenic exposure was
      estimated through information obtained from a personal interview according to a
      structured questionnaire and the arsenic content in artesian well water of the
      villages. Cumulative arsenic exposure (CAE) was calculated as the sum of the
      products multiplying the arsenic concentration in artesian well water (mg/l) by
      the duration of drinking the water (years) in consecutive periods of living in
      the different villages. Among the subjects, 78 cases (16.9%) were diagnosed as
      having IHD. The prevalence rates of IHD for the age groups of 30-39, 40-49, 50
      59, and >/=60 years were 4.9, 7.5, 16.8, and 30.7%, respectively (P<0.001). For
      those with CAE of 0, 0.1-14.9 and >/=15 mg/l-years, the prevalence rates of IHD
      were 5.2, 10.9 and 24.1%, respectively (P<0.001). The odds ratios (95% confidence
      intervals) for IHD were 1.60 (0.48, 5.34), and 3.60 (1.11, 11.65), respectively,
      for those with CAE of 0.1-14.9 and >/=15.0 mg/l-years, when compared with those
      lacking drinking water exposure to arsenic after multivariate adjustment. It is
      concluded that IHD in the arseniasis-hyperendemic villages in Taiwan was
      associated with long-term arsenic exposure.

PMID- 12505430
TI  - A field study conducted at Kidston Gold Mine, to evaluate the impact of arsenic
      and zinc from mine tailing to grazing cattle.
AB  - The grazing trial at Kidston Gold Mine, North Queensland, was aimed specifically
      to assess the uptake of metals from the tailing and the potential for
      unacceptable contamination of saleable meat. Further aims included estimating
      metal dose rates and identifying potential exposure pathways including plant
      uptake of heavy metals, mine tailings adhered to plants and direct ingestion of
      mine tailing. It was found that of the 11 metals analysed (As, Zn, Co, Cd, Cr,
      Sn, Pb, Sb, Hg, Se and Ni) in the animal's liver, muscle and blood during the 8
      month trial period, only accumulation of arsenic and zinc occurred. A risk
      assessment including these two metals was conducted to determine the potential
      for chronic metal toxicity and long-term contamination, using the estimates of
      metal dose rate. It was concluded that no toxicity or long-term contamination in
      cattle was likely at this site. Management procedures were therefore not required
      at this site; however, the results highlight percent ground cover and standing
      dry matter (DM) as important factors in decreasing metal exposure from direct
      ingestion of tailings and dust adhered to plants.

PMID- 12505431
TI  - Arsenic speciation in the urine and hair of individuals exposed to airborne
      arsenic through coal-burning in Guizhou, PR China.
AB  - The extent of exposure of residents of Changqing (Guizhou, PR China) to arsenic
      through coal-burning was investigated. Despite the low coal-arsenic content
      (56.3+/-42.5 mg As kg(-1)) when compared with coals collected at different
      location and times from the same province, more than 30% of the study subjects
      have shown symptoms of arsenicosis. Coal, urine, hair, and water samples were
      collected in mid-September 2001 and analysed for arsenic. The average urinary and
      hair-arsenic concentrations in the exposed subjects were 71.4+/-37.1 microg As g(
      1) creatinine (control 41.6+/-12.1) and 7.99+/-8.16 mg kg(-1), respectively. A
      positive correlation between the hair and urinary-arsenic concentration
      (R(2)=0.601) was found. There was no significant difference between females and
      males for both urinary and hair-arsenic concentrations. Females were found to
      have a higher dimethylarsinic acid but lower percentages of inorganic arsenic and
      monomethylarsonic acid in their urine than males.

PMID- 12505432
TI  - Determinants of inorganic arsenic methylation capability among residents of the
      Lanyang Basin, Taiwan: arsenic and selenium exposure and alcohol consumption.
AB  - The objective of this study was to assess individual variation in inorganic
      arsenic methylation capability and the association between selenium levels in
      urine and blood, and inorganic arsenic methylation capability among residents of
      the Lanyang Basin who drank groundwater and were exposed to high concentrations
      of inorganic arsenic. According to the arsenic concentration of their drinking
      water, they were equally and randomly classified into four groups of 252 persons.
      It turned out that the higher the concentration of arsenic in well water was and
      thus the cumulative arsenic exposure, the higher the total inorganic arsenic
      metabolites in urine (total As(i)) and the overall inorganic and organic arsenic
      in urine (overall As(i+o)) were. The percentage of inorganic arsenic
      significantly decreased and the DMA percentage significantly increased as the
      concentration of urinary selenium and serum alpha-tocopherol increased. It
      appeared that urinary selenium levels increased the metabolism by methylation of
      arsenic, a finding that requires further investigation.

PMID- 12505433
TI  - A global perspective on cadmium pollution and toxicity in non-occupationally
      exposed population.
AB  - Cadmium is a non-essential element that has high rates of soil to plant
      transference compared with other non-essential elements, and certain plant
      species accumulate large amounts of cadmium from low cadmium content soils. In
      this paper, levels of cadmium found in major food groups are highlighted together
      with cadmium levels found in liver and kidney samples from non-occupationally
      exposed populations. Data on human kidney cadmium levels identified recently,
      including the study in our own laboratory, are compared with older studies. Human
      tissue cadmium contents showed large variations among individuals, but sources of
      the variation remain unknown. Exposure levels of 30-50 microg per day have been
      estimated for adults and these levels have been linked to increased risk of bone
      fracture, cancer, kidney dysfunction and hypertension. Increased mortality was
      found among individuals showing signs of cadmium renal toxicity compared with
      those without such signs, suggesting that renal toxicity may be an early warning
      of complications, sub-clinical or clinical morbidity.

PMID- 12505434
TI  - Potential for early involvement of CYP isoforms in aspects of human cadmium
      toxicity.
AB  - This paper investigates the possible link between non-workplace cadmium (Cd)
      exposure, cytochrome P450 expression and hypertension. We present results of our
      investigation into the relationships between liver and kidney Cd burdens and the
      abundance of the CYP isoform 4A11. Our data show associations between non
      workplace Cd exposure and changes in the abundance of hepatic and renal cortical
      CYP4A11. In liver the levels of immunochemically detectable CYP4A11 were
      positively correlated with tissue Cd content while in contrast CYP4A11 abundance
      was inversely correlated with kidney Cd burden. These differences are most likely
      related to the different Cd burden of the tissues. These observations suggest the
      potential for involvement of Cd as a mediator of CYP4A11 expression in kidney
      cortex and indicate that elevations in kidney Cd content may be involved in
      hypertension via alteration of the expression of this particular isoform.
      Potential mechanisms by which Cd may alter CYP4A11 expression are discussed
      briefly.

PMID- 12505435
TI  - Selenium status of low-selenium area residents: Polish experience.
AB  - The concentration of selenium (Se) in human organism varies widely between
      geographical areas depending on its content in soil and plants, dietary Se
      intake, bioavailability and retention, mineral interactions and other factors.
      The study includes healthy inhabitants of different regions of Poland; pregnant
      women, lactating women, children from 0 to 15 years of age and adults. Systematic
      determinations allow us to observe changes of the concentration of Se in time,
      which may be significant for developing preventive action. The results obtained
      confirm our thesis that Se concentration in the blood of the inhabitants of
      Poland depends on the region of the country. In recent years, in a considerable
      number of Polish inhabitants, the concentration of Se in blood plasma has been
      relatively low-about 50-55 microg/l, and the calculated daily dietary intake
      about 30-40 microg/day. The low levels of the element in the blood and urine are
      probably due to its deficiency in the diet.

PMID- 12505436
TI  - Essentiality and toxicity of selenium and its status in Australia: a review.
AB  - Selenium (Se) is an essential trace element for animals and humans because of its
      role in an antioxidant enzyme glutathione peroxidase. This enzyme protects cell
      membranes from damage caused by the peroxidation of lipids. The paper provides an
      overview of the effects of Se toxicity and deficiency in humans and animals. It
      is well established that Se deficiency causes health implications in humans and
      animals. Se is also very toxic and can cause Se poisoning (selenosis) in humans
      and animals. In Australia, Se deficiency has caused health problem to livestock;
      however, the problems were eliminated after the introduction of Se
      supplementation. Se toxicity has also been reported in some regions of Australia
      as a result of livestock feeding on Se accumulative plant species. The major
      source of Se is diet, and in many regions of the world the levels of Se in the
      soils generally reflect the Se status in human populations. In foods, the
      bioavailability and toxicity of Se depend on its chemical forms. Generally,
      organic forms of Se are more bioavailable and less toxic than the inorganic forms
      (selenites, selenates). The Se status in the Australian population and how this
      is compared with the rest of the world is also discussed.

PMID- 12505437
TI  - Aluminium and fluoride contents of tea, with emphasis on brick tea and their
      health implications.
AB  - Tea plant takes up a large quantity of aluminium (Al) and fluoride (F) from
      acidic soils. It has been known that fluorosis can be developed for people who
      consume a large quantity of tea made from brick tea, a low quality tea consisting
      mainly of old tea leaves in China. In addition, it has been claimed that
      Alzheimer's disease (AD) is linked with the Al content in the human brain.
      Therefore, the high Al content in tea, especially brick tea is also a concern.
      This article reviews the basis background on tea including classification, growth
      conditions, types of tea leaves and their production, and processing of tea.
      Special emphasis is made on the transfer of Al and F from soil to tea plant and
      then to tea liquor. Health implications of drinking a large quantity of tea
      liquor especially those made from brick tea are discussed. Recommendations are
      suggested to reduce the uptake of these two elements by tea plant, and lower
      their contents in tea products.

PMID- 12505438
TI  - Toxicity assessment of sediments containing tributyltin around Hong Kong harbour.
AB  - Rather high levels of tributyltin (TBT) in sediments were found in certain areas
      around the Hong Kong coastline. Sediments from two contaminated sites (Tsing Yi
      and Yam O) and two clean sites were used to study the release of TBT contaminants
      from resuspended sediment to the water column by elutriate tests. The chemical
      analysis data of elutriates were compared with the effective or lethal
      concentrations from the toxicity tests of spiked solution using marine microalga
      (Dunaliella tertiolecta) and benthic invertebrate (Melita koreana) to assess the
      potential ecotoxicological impacts arising from the dredging work. Concentrations
      of TBT in filtered sediment elutriates were mostly below 0.002 microg/l which
      suggested that very little of TBT was released in soluble form. The lethal
      toxicity of TBT for the invertebrate expressing as 10 day-LC(50) was 2.31
      microg/l for TBT and the alga expressing as 48 h-EC(50) was 0.46 microg/l. The
      results of this evaluation demonstrated that the release of TBT from two
      contaminated sites during dredging was unlikely to attain the effective or lethal
      concentrations on the two test species.

PMID- 12505439
TI  - Influence of malathion pretreatment on the toxicity of anilofos in male rats: a
      biochemical interaction study.
AB  - Toxicity of organophosphates stems mainly from the accumulation of acetylcholine
      due to inhibition of acetylcholinesterase (AChE). The consequences of excess
      acetylcholine depend on the events initiated by the interaction of acetylcholine
      with cholinergic receptors. Lipid peroxidation (LPO) induced by organophosphates
      also seems to be mediated via cholinergic receptors. Anilofos is a widely used
      thionoorganophosphate herbicide, while malathion is a thionoorganophosphate
      insecticide. Thionoorganophosphates undergo mixed function oxidase (MFO)
      catalyzed bioactivation to oxons and can induce cholinergic crisis in mammals.
      Thus, factors (e.g. exposure to certain xenobiotics) which alter the MFO
      activity, can be assumed to affect the toxicity of these organophosphates. It was
      investigated in rats if malathion as an inhibitor of MFO can alter the toxicity
      of anilofos, examining certain biochemical traits in blood, brain and liver.
      Malathion or anilofos and their combination did not produce any obvious signs of
      toxicity. Malathion did not alter the anticholinesterase action of anilofos in
      blood, brain and liver. LPO was increased in erythrocytes, brain and liver with
      anilofos or malathion and their combination. Production of lipid peroxide in
      brain of malathion-pretreated rats given anilofos was significantly greater than
      in rats given anilofos alone. Malathion decreased glutathione (GSH) contents of
      liver and blood. Glutathione-S-transferase (GST) activity was decreased in the
      liver with malathion and its combination with anilofos. Total adenosine
      triphosphatase (ATPase) activity was not affected. Activities of Mg(2+)-ATPase
      and Na(+)-K(+)-ATPase were increased in the liver and erythrocytes, respectively,
      with the pesticide combination. Protein level in plasma was decreased with
      malathion and its combination with anilofos, but only with the combination in the
      liver. Results of the study indicate that malathion pretreament may not
      essentially alter the anticholinesterase action of anilofos, but may enhance
      anilofos-mediated oxidative damage to rat brain.

PMID- 12505440
TI  - Nickel and cobalt activate complement factor C3 faster than magnesium.
AB  - We have found that incubation of heparin plasma with Ni(2+) or Co(2+) at
      concentrations below 100 microM can stimulate the conversion of complement factor
      C3 to C3b faster than magnesium, which is the natural cofactor in the alternative
      complement activation. This conversion was monitored by light absorbance
      measurement after separation by isotachophoresis, immunofixation and protein
      staining. The generation of C3b stimulated by these metals (<0.5 mM) proceeds up
      to about four times faster than the stimulation by Mg(2+). Half of total C3 in
      the incubation media was converted by Ni(2+) or Co(2+) at 0.5 mM after 20 min at
      37 degrees C. Increasing Ni(2+) concentrations over 0.5 mM decreased the C3
      conversion rate. Activation of C3 stimulated by Ni(2+), Co(2+) and Mg(2+) was
      concomitant with the conversion of complement factor B to Bb, but complement
      factor C4 was not affected by the activation. The conversion of B to Bb was
      monitored after separation by isotachophoresis and immunoblotting. Other divalent
      metal ions tested, namely Ca(2+), Ba(2+), Cu(2+) and Zn(2+), did not stimulate
      the complement cascade. We postulate that the increased rate of C3-fragment
      production induced by nickel or cobalt ions is central for the immunotoxicity of
      these metals.

PMID- 12505441
TI  - Lack of susceptibility of heterozygous p53-knockout CBA and CIEA mice to
      phenolphthalein in a 6-month carcinogenicity study.
AB  - Phenolphthalein has carcinogenic activity, causing malignant lymphomas in B6C3F1
      mice at a dietary dose of 3000 ppm in a 2-year carcinogenicity study and in
      female heterozygous p53-knockout TSG mice (C57BL/6 background) at the same dose
      in a 6-month study. To examine whether carcinogenic potential of phenolphthalein
      can be detected in other p53-knockout mouse [p53 (+/-)] strains such as p53 (+/-)
      CBA mice or p53 (+/-) CIEA mice (C57BL/6 background) and their littermates, they
      were given a diet containing 0, 6000 or 12000 ppm for 6 months. Unequivocal
      induction of neoplastic lesions was not apparent, suggesting that p53 (+/-) CBA
      mice and p53 (+/-) CIEA mice are resistant to the induction of malignant
      lymphomas by the treatment of phenolphthalein.

PMID- 12505442
TI  - Placental transfer of mercury in pregnant rats which received dental amalgam
      restorations.
AB  - Mercury vapor released from one, two and four amalgam restorations in pregnant
      rats and mercury concentrations in maternal and fetal organs were studied. Dental
      treatment was given on day 2 of pregnancy. Mercury concentration in air samples
      drawn from each metabolism chamber with a rat were measured serially for 24 h on
      days 2, 8 and 15 of pregnancy. On each day of pregnancy, the amount of mercury in
      24 h air samples was in proportion to the amalgam surface areas. Linear
      regression analysis showed relatively high correlation coefficients between the
      mercury content and amalgam surface areas, and the coefficients were
      statistically significant. A highly significant correlation was also found
      between the number of amalgam fillings and their surface areas. Mercury
      concentrations in major maternal organs with one, two and four amalgam fillings
      tended to increase with the increasing amalgam surface areas. Spearman's rank
      correlation test revealed significant correlations in the brain, liver, kidneys
      and placenta but not in the lung. Furthermore, significant correlations were also
      found between the mercury concentrations in all maternal organs and the amount of
      mercury in 24 h air samples on day 15 of pregnancy. Mercury concentrations in
      fetal brain, liver and kidneys were much lower than those of the dams but liver
      and kidneys showed positive correlations between the mercury content and maternal
      amalgam surface areas. Similar correlations were observed between the mercury
      concentrations in fetal organs and the amount of mercury in 24 h air samples on
      day 15 of pregnancy. In fetal brain, no significant correlations were found
      between either maternal amalgam surface areas or the amount of mercury in 24 h
      samples on day 15 of pregnancy but significant uptake of mercury was found in the
      samples from the dams given four amalgam fillings. The results of the present
      study demonstrated that mercury vapor released from the amalgam fillings in
      pregnant rats was distributed to maternal and fetal organs in dose-dependent
      amounts of the amalgam fillings.

PMID- 12505443
TI  - Concentration-dependence of biomarkers of exposure of methylenediphenyl
      diisocyanate following acute inhalation exposure of rats.
AB  - Rats were nose-only exposed for 6 h to polymeric methylenediphenyl-diisocyanate
      (pMDI). Concentrations varied from 0.12 to 12.7 mg/m(3) using a highly respirable
      aerosol. In regard to the concentration of the monomeric fraction of MDI
      contained in pMDI, the lowest concentration was in the range of the current
      workplace limit of MDI which is 0.05 mg/m(3). Biomarkers of exposure were
      determined in hydrolyzed urine (collection started after cessation of exposure
      for approximately 18 h; acid hydrolysis) and hydrolyzed hemoglobin (collection of
      blood approximately 20 h after cessation of exposure; alkaline hydrolysis). The
      determination revealed two-order of magnitudes higher yields of the biomarkers in
      urine when compared to hemoglobin. The concentration of analytes from the
      respective biological matrix was highly correlated with the airborne
      concentration of pMDI whilst their yields exhibited a reciprocal relationship to
      the airborne concentration of pMDI. A linear relationship could only be
      demonstrated by using a logarithmic transformation of data. With respect to the
      amount of 4,4'-methylenediphenyldianiline creatinine (MDA/g creatinine) in
      hydrolyzed urine of rats at an exposure level similar to the current workplace
      concentration of MDI, this marker of exposure was approximately 10-times lower in
      rats than predicted for humans. This suggests that the extrapolation of animal
      data to man as well as from one exposure regimen to another, without taking into
      consideration the different deposition/retention patterns of vapors (<or=0.05
      mg/m(3)) or aerosols of MDI, might be error prone. In summary, taking into
      account previous and current experimental evidence, these data substantiate
      further that the formation of MDI-related biomarkers appear to be governed by
      spontaneously occurring, scavenging reactions at the portal-of-entry. Comparison
      of MDI with its corresponding amine support that the analytes determined stem
      from conjugated MDI rather than in vivo hydrolyzed MDI.

PMID- 12505444
TI  - A comparison of gene expression changes in response to diethylstilbestrol
      treatment in wild-type and p53+/- hemizygous knockout mice using focussed arrays.
AB  - We have investigated the hepatic response of female C57BL/6J wild-type and p53(+/
      ) hemizygous mice to genotoxic levels of diethylstilbestrol (DES) using cell
      cycle and apoptosis-focussed cDNA expression arrays. DES induced the expression
      of 12 genes (bad, bax, bcl-x, caspase-1, p53, cyclin D3, GADD45, p21, p15, p27,
      p57 and Skp1) and down-regulated the expression of eight genes (bcl-2, caspase-2,
      caspase-7, caspase-8, E124, iNOS, mdm2 and NFkappab1) at twofold or greater
      levels. Taken together, these changes were strongly reflective of the induction
      of apoptosis in the livers of DES-treated mice. Of those genes showing the
      greatest changes in response to DES, p53, p21 and p57 were expressed at 2.1, 1.7
      and 1.6 times greater (respectively) in wild-type mice as compared with p53(+/-)
      hemizygous mice. Differences in p53, p21 and bax expression were confirmed by RT
      PCR and we conclude that the compromised response of p53(+/-) mice is likely to
      play a central role in the earlier appearance of tumours in this model, following
      exposure to genotoxic carcinogens.

PMID- 12505445
TI  - Placental lead and outcome of pregnancy.
AB  - Prenatal exposure to lead produces toxic effects in the human fetus, including an
      increased risk of preterm delivery, low birth weight and impaired mental
      development. Since we believe that placental lead could be a good biomarker for
      fetal exposure, we assessed the relation of placental lead to intrauterine fetal
      growth and some adverse outcomes of pregnancy. Low concentrations of lead were
      found in the population studied (N, 89; mean, 113.4 ng/g dry tissue; S.D., 58.0).
      The cases were divided into two groups based on delivery outcome. In the group of
      placentas from premature rupture of membranes and preterm labor (gestational age
      <or=37 weeks), higher lead levels were recorded than in the placentas from term
      pregnancies. The proportion of abnormal pregnancy outcome in the group of
      placentas with lead concentrations above 120 ng/g was 40.6 versus 8.8% in
      placentas below this concentration. Higher placental lead levels, in general,
      were not related to smaller weight, head and abdominal circumference or shorter
      length at birth.

PMID- 12505446
TI  - The effects of acute pesticide exposure on neuroblastoma cells chronically
      exposed to diazinon.
AB  - Speculation about potential neurotoxicity due to chronic exposure to low doses of
      organophosphate (OP) pesticides is not yet supported by experimental evidence.
      The objective of this work was to use a cell culture model of chronic OP exposure
      to determine if such exposure can alter the sensitivity of nerve cells to
      subsequent acute exposure to OPs or other compounds. NB2a neuroblastoma cells
      were grown in the presence of 25 microM diazinon for 8 weeks. The OP was then
      withdrawn and the cells were induced to differentiate in the presence of various
      other pesticides or herbicides, including OPs and OP-containing formulations. The
      resulting outgrowth of neurite-like structures was measured by light microscopy
      and quantitative image analysis and the IC(50) for each OP or formulation was
      calculated. The IC(50) values in diazinon-pre-exposed cells were compared with
      the equivalent values in cells not pre-exposed to diazinon. The IC(50) for
      inhibition of neurite outgrowth by acute application of diazinon, pyrethrum,
      glyphosate or a commercial formulation of glyphosate was decreased by between 20
      and 90% after pre-treatment with diazinon. In contrast, the IC(50) for pirimiphos
      methyl was unaffected and those for phosmet or chlorpyrifos were increased by
      between 1.5- and 3-fold. Treatment of cells with chlorpyrifos or with a second
      glyphosate-containing formulation led to the formation of abnormal neurite-like
      structures in diazinon-pre-exposed cells. The data support the view that chronic
      exposure to an OP may reduce the threshold for toxicity of some, but by no means
      all, environmental agents.

PMID- 12505447
TI  - Late administration of COX-2 inhibitors minimize hepatic necrosis in chloroform
      induced liver injury.
AB  - Our previous studies have described the protective effects of hepatoprotective
      agents against liver injury elicited by chloroform even when given 24 h after the
      toxicant, at a time when the liver injury is taking place and rapidly developing.
      However, the mechanisms involved in this protection remain unknown. The
      cytoprotective mechanism of these hepatoprotectants such as DMSO, may be due to a
      dramatic shift in the production of prostaglandins that are responsible for
      controlling the degree of inflammatory response that can affect blood flow in the
      liver. In this study, NS-398, a specific COX-2 inhibitor, and indomethacin, a COX
      1 and COX-2 inhibitor, were administered 24 h after chloroform dosing to
      determine their effect on liver injury in Sprague-Dawley rats. The extent of
      necrosis was evaluated by H&E staining, while injury to hepatocytes was evaluated
      by measuring plasma levels of alanine transaminase (ALT). Both COX inhibitors,
      indomethacin and NS-398, prevented an increase in (ALT) at 48 h after initial
      toxicant insult and attenuated further liver necrosis. No changes in cellular
      proliferative activity occurred in all the treatment groups, which indicates that
      protection from the Cyclooxygenase (COX) inhibitors did not have an effect on
      regeneration of cells at 32 and 48 h. These results indicate COX inhibitors
      provide a significant protective effect on liver cells against CHCl(3) injury and
      may provide further insight into therapeutic interventions against
      hepatotoxicants.

PMID- 12505448
TI  - Effect of malathion on apoptosis of murine L929 fibroblasts: a possible mechanism
      for toxicity in low dose exposure.
AB  - While acute organophosphorous compound poisoning due to inhibition of
      acetylcholinesterase is a well-established clinical entity, the existence of
      chronic poisoning due to exposure to low levels of organophosphorous compounds
      (below the threshold required for cholinergic clinical symptoms) is a hotly
      debated issue. In this study, we have evaluated the effects of noncholinergic
      doses of malathion (0.01-20 microM) on apoptosis of murine L929 fibroblasts.
      Employing flow cytometric and caspase activation analyses we demonstrate that
      malathion induces apoptosis in L929 cells in a dose- and time-dependent manner.
      The initiator caspases (caspase-8 and caspase-9) as well as the effector caspase
      (caspase-3) were activated by the treatment of L929 cells with malathion.
      Exposure of L929 cells to malathion in the presence of a general inhibitor of
      caspase, z-VAD-FMK abolished the apoptotic effect of the compound. In addition,
      malathion induced an increase in the expression of the pro-apoptotic protein p53.
      However, the induction of p53 expression was subsequent to activation of the
      caspase cascades. The present findings suggest, that the cytotoxicity of
      malathion at noncholinergic doses is mediated through caspase-dependent
      apoptosis.

PMID- 12505449
TI  - Assessment of glycosylation-dependent cell adhesion molecule 1 as a correlate of
      allergen-stimulated lymph node activation.
AB  - Early changes in gene expression have been identified by cDNA microarray
      technology. Analysis of draining auricular lymph node tissue sampled at 48 h
      following exposure to the potent contact allergen 2,4-dinitrofluorobenzene (DNFB)
      provided examples of up- and down-regulated genes, including onzin and guanylate
      binding protein 2, and glycosylation-dependent cell adhesion molecule 1 (GlyCAM
      1), respectively. Allergen-induced changes in these three genes were confirmed in
      dose-response and kinetic analyses using Northern blotting and/or reverse
      transcription-polymerase chain reaction techniques. The results confirmed that
      these genes are robust and relatively sensitive markers of early changes provoked
      in the lymph node by contact allergen. Upon further investigation, it was found
      that altered expression of the adhesion molecule GlyCAM-1 was not restricted to
      treatment with DNFB. Topical sensitization of mice to a chemically unrelated
      contact allergen, oxazolone, was also associated with a decrease in the
      expression of mRNA for GlyCAM-1. Supplementary experiments revealed that changes
      in expression of this gene are independent of the stimulation by chemical
      allergens of proliferative responses by draining lymph node cells. Taken together
      these data indicate that the expression of GlyCAM-1 is down-regulated rapidly
      following epicutaneous treatment of mice with chemical allergens, but that this
      reduction is associated primarily with changes in lymph node cell number, or some
      other aspect of lymph node activation, rather than proliferation.

PMID- 12505450
TI  - Induction of oxidative stress by bisphenol A in the epididymal sperm of rats.
AB  - Bisphenol A has been shown to affect the reproduction of male rats and mice.
      However, the mechanism of action of bisphenol A on the epididymal sperm is not
      elucidated. The present study was undertaken to evaluate the effect of bisphenol
      A on the antioxidant system of rat epididymal sperm. Bisphenol A was administered
      orally to male rats at the dose levels of 0.2, 2 and 20 microg/Kg body weight per
      day for 45 days. After 24 h of the last treatment, rats were weighed and killed
      using anesthetic ether. The body weight of treated rats did not show significant
      change as compared with the corresponding control groups. In bisphenol A-treated
      rats there was a significant decrease in the weight of the testis and epididymis;
      the weight of ventral prostate increased significantly whereas there was no
      significant change in the weight of seminal vesicles as compared with the
      corresponding group of control animals. Sperm collected from the epididymis were
      used for sperm count and biochemical estimations. Administration of bisphenol A
      caused a reduction in the epididymal sperm motility and sperm count in a dose
      dependent manner. The activities of superoxide dismutase, catalase, glutathione
      reductase and glutathione peroxidase were decreased while the levels of H(2)O(2)
      and lipid peroxidation increased significantly in the treated rats as compared
      with the corresponding group of control animals. The results suggested that
      graded doses of bisphenol A elicit depletion of antioxidant defence system and
      induce oxidative stress in epididymal sperm of rats. In conclusion, the adverse
      effect of bisphenol A on male reproduction may be due to induction of oxidative
      stress in sperm.

PMID- 12505451
TI  - Neuroprotective efficacy of pharmacological pretreatment and antidotal treatment
      in tabun-poisoned rats.
AB  - To study the influence of pharmacological pretreatment (PANPAL) and antidotal
      treatment (obidoxime plus atropine) on tabun-induced neurotoxicity, male albino
      rats were poisoned with a lethal dose of tabun (280 microg/kg i.m.; 100% of
      LD(50) value) and observed at 24 h and 7 days following tabun challenge. The
      neurotoxicity of tabun was evaluated using a functional observational battery
      (FOB) and an automatic measurement of motor activity. Pharmacological
      pretreatment as well as antidotal treatment were able to eliminate most of tabun
      induced neurotoxic effects observed at 24 h following tabun poisoning. However,
      there was not significant difference between the efficacy of PANPAL and antidotal
      treatment to eliminate tabun-induced neurotoxicity in rats. The combination of
      PANPAL pretreatment and antidotal treatment seems to be slightly more effective
      in the elimination of tabun-induced neurotoxicity in rats at 24 h following tabun
      challenge in comparison with the administration of PANPAL pretreatment or
      antidotal treatment alone. At 7 days following tabun poisoning, very few
      neurotoxic signs in tabun-poisoned rats were observed regardless of
      administration of pharmacological pretreatment or antidotal treatment. Thus, our
      findings confirm that the combination of pharmacological pretreatment and
      antidotal treatment is not only able to protect the experimental animals from the
      lethal effects of tabun but also to eliminate most of tabun-induced signs of
      neurotoxicity in tabun-poisoned rats.

PMID- 12505452
TI  - Different behaviour of 63Ni and 59Fe during absorption in iron-deficient and iron
      adequate jejunal rat segments ex vivo.
AB  - Nickel exhibits low oral toxicity. It shares the absorptive pathways for iron,
      though there are substantial quantitative differences in handling of both metals.
      To analyse these differences more closely, jejunal segments from iron-deficient
      and iron-adequate rats were luminally perfused ex vivo with 59Fe and 63Ni at six
      different concentrations (1-500 micromo1/l) under steady state conditions. 59Fe
      over-all absorption increased 2.0-4.6-fold in iron-deficiency at luminal
      concentrations between 1 and 100 micromol/l, while 63Ni absorption increased to a
      much lower extent (2.6-fold at 1 micromol/l and 1.5-fold at higher luminal
      concentrations). Moreover, there was a 5-7-fold higher concentration for 63Ni in
      the jejunal tissue than in the absorbate at luminal concentrations above 50
      micromol/l which was not observed at 1 micromol 63Ni/l and not for 59Fe. 63Ni
      tissue load showed a linear and a saturable fraction. In iron-deficiency the
      saturable 63Ni fraction increased 4-fold as compared to only 1.5-fold increments
      for 59Fe. Moreover, a substantially higher share of 63Ni was retained in the
      jejunal tissue at high as compare to low luminal concentrations after perfusion
      had been continued without luminal radioactivity. This was not found for 59Fe and
      suggests a concentration-dependent block of 63Ni export across the enterocytes'
      basolateral membrane. To explain these results one may speculate that 63Ni may
      bind more tightly to tissue ligands than 59Fe due to the higher thermodynamic and
      kinetic stability of nickel complexes. In particular, nickel may bind to a
      basolateral population of metal carriers and block its own basolateral transfer
      in a concentration-dependent manner. Tight 63Ni binding to non-specific jejunal
      ligands is responsible for the unaltered high linear fraction of jejunal 63Ni
      load in iron-deficient and iron-adequate segments. Binding of 63Ni to food and
      tissue ligands in the small intestine may, thus, be a likely explanation for the
      low oral nickel toxicity.

PMID- 12505453
TI  - Exogenous oestrogen as an alternative to food allergy in the aetiology of
      angioneurotic oedema.
AB  - Although frequently reported as an aetiology for chronic angioneurotic oedema or
      urticaria, food allergy is often a diagnosis proposed in the absence of more
      convincing evidence, as illustrated by the disappointing results of eviction
      regimens. We report a series of women with an initial diagnosis of food allergy,
      but in whom the role of oral contraceptives was subsequently demonstrated.
      Detailed medical history was obtained from 26 young women presenting with chronic
      angioneurotic oedema or urticaria initially attributed to food allergy, but in
      whom C1-esterase inhibitor (C1 INH) deficiency was demonstrated. We investigated
      the effects of oral contraception on C1 INH levels, C1 INH activity and clinical
      symptoms of these patients. Discontinuation of oral contraception induced an
      increase in C1 INH levels and C1 INH activity, associated with recovery or marked
      improvement of the clinical symptoms formerly attributed to food allergy. The
      relatively high frequency of women taking cyproterone acetate in this population
      appeared to be a remarkable finding. Replacement of the initial contraception
      containing ethinylestradiol by a progestogen maintained or even accentuated these
      good therapeutic results. Exogenous oestrogens, such as those contained in most
      oral contraceptives, may play an iatrogenic role in the aetiology of chronic
      angioneurotic oedema or urticaria.

PMID- 12505454
TI  - Effects of a superantigen-antibody recombinant fusion protein (r-C242 Fab-SEA) on
      toxicological responses in the anaesthetised rabbit.
AB  - The objective was to study toxin-induced effects on physiological parameters in
      the rabbit and whether these parameters show dose-response and co-variation after
      administration of a recombinant fusion protein between staphylococcal enterotoxin
      (SE) and the Fab fragment of an antibody. Rabbits are very sensitive to SE toxins
      and the cardiovascular and immune effects are similar to those observed in septic
      shock in man. The test compound, r-C242 Fab-SEA, was administered intravenously
      to anaesthetised New Zealand white rabbits at doses in the range of 0.00005-50
      microg/kg. All rabbits were checked for titres of anti-SEA antibodies before
      entering the experiment, since they could neutralise the effect of the test
      compound. Heart rate, blood pressure and body temperature were continuously
      monitored before and during 6 h after dosing. Immediately before the start of
      administration and 3 and 6 h during the experiment, blood gases (pO(2) and
      pCO(2)), pH, haematology, clinical chemistry, cytokine response (TNF-alpha) and
      trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg and Pb) were measured. No mortality
      occurred, but at 50 microg/kg severe adverse clinical signs developed. The
      decrease in blood pressure was weakly dose-related. Heart rate, ECG, body
      temperature, pCO(2) and pH were not affected by the treatment. pO(2) tended to
      increase as a function of time, but not in relation to dose. WBC and PLT
      decreased dose dependently. TNF-alpha was not affected by the treatment. The
      major effects on clinical chemistry were a dose-dependent increase in AST and
      creatinine. Potassium and urea showed dose dependent increases, mainly at higher
      doses, though these changes were of less value for drug selection purposes. Trace
      element changes were observed, including an increase in Mn and a decrease of Zn
      at all doses. The Cu/Zn ratio decreased below normal at low doses, whereas at
      high doses in which adverse effects developed, it increased above normal. Post
      mortem examination revealed minimal to moderate dose-related granulocytic
      infiltrate in the lungs. The present study showed dose-response and co-variation
      between several changes in cardiovascular, haematology, clinical chemistry and
      trace element parameters during the initial phase of toxin-induced effects
      preceding a possible lethal endpoint and associated patho-physiological changes.

PMID- 12505455
TI  - Susceptibility of Lactobacillus spp. to antimicrobial agents.
AB  - Bacteria used as probiotics or in starter cultures may serve as hosts of
      antibiotic resistance genes, which can be transferred to pathogenic bacteria.
      Before launching a starter culture or a probiotic product into the market, it is
      therefore important to verify that the single bacterial isolates (strains) do not
      contain transferable resistance genes. A study has been undertaken to establish
      the levels of susceptibility of Lactobacillus spp. to various antimicrobial
      agents. This is a prerequisite for differentiating putative transferable
      resistance from natural resistance. A selection of 62 strains has been screened
      with the use of the Etest (ABBiodisk, Stockholm, Sweden) for their susceptibility
      to 25 antimicrobial agents. The strains belonged to the following species:
      Lactobacillus plantarum/pentosus, L. rhamnosus, L. paracasei, L. sakei, L.
      curvatus and species of the L. acidophilus group: L. johnsonii, L. crispatus, L.
      gasseri, and L. acidophilus. The results from the Etests have shown that the
      level of susceptibility to the antimicrobial agents is species-dependent. For the
      following antimicrobial agents, susceptibility varied several folds between
      species: vancomycin, teicoplanin, tetracycline, norfloxacin, ciprofloxacin,
      fusidic acid, and clindamycin. The differences between the species were more
      subtle for the rest of the tested antimicrobial agents. On the basis of the
      result, it was possible to suggest minimal inhibition concentrations (MICs) for
      the individual Lactobacillus species to be used as a microbiological breakpoint
      when screening strains for transferable resistance genes.

PMID- 12505456
TI  - Inactivation of Salmonella enteritidis during boiling of eggs.
AB  - A series of inactivation curves for Salmonella enteritidis were determined for
      boiling eggs using different conditions of time and temperature. No significant
      influence of egg weight could be found on the temperature evolution in the yolk.
      The inactivation curves consistently showed an initial slow decline in bacterial
      number at lower temperatures, after which a very rapid inactivation took place.
      It was not possible to reproduce this behavior using a traditional inactivation
      model. A pragmatic model existing in two parts was therefore constructed. When
      the temperature is below a certain threshold, the inactivation follows a second
      order temperature dependence. Above the temperature threshold, standard Bigelow
      inactivation kinetics are assumed. This model could describe the data reasonably
      well, provided that the decimal reduction time in the Bigelow model was assumed
      to be different for a fast or slow heating process, respectively. The results
      suggest that the bacteria are more resistant towards a slower heating process,
      which is confirmed by analyzing the raw data. A fail-safe model can be obtained
      by using the parameters associated with the slow heating process. The statistical
      properties of the calibrated model are satisfactory, and a cross-validation shows
      that it can be used for egg boiling conditions outside its calibration range.

PMID- 12505457
TI  - Thermal inactivation of Pediococcus sp. in simulated apple cider during high
      temperature short-time pasteurization.
AB  - Prompted by concerns regarding outbreaks of food-borne illness which have
      occurred due to the consumption of commercial, nonpasteurized fruit juices
      contaminated with Escherichia coli O157:H7, the US Food and Drug Administration
      and Canadian Food Inspection Agency are considering several new safety standards
      to apply to fresh juices, including mandatory pasteurization of all apple cider.
      In support of these initiatives, a study was conducted to evaluate the
      pasteurization of simulated cider using a heat-resistant nonpathogenic test
      bacterium, Pediococcus sp. NRRL B-2354. Thermal inactivation of the Pediococcus
      sp. was determined using a pilot scale high-temperature short-time (HTST)
      pasteurizer with a plate heat exchanger. The cumulative lethal effect, or
      pasteurization effect (PE), was obtained by converting times at different
      temperatures in the various sections of the pasteurizer to the equivalent time at
      the reference temperature (72 degrees C). PE was then related by a simple linear
      function to the log(10) of the percentage of viable counts with a power
      transformation of the PE values to improve linear fit. r(2) values for the four
      Pediococcus sp. trials varied from 0.921 to 0.981. Intertrial variation was
      incorporated into the model using @RISK simulation software. Output from
      simulations confirmed that treatment at 71 degrees C for 16 s can ensure a 5-log
      reduction of Pediococcus sp.

PMID- 12505458
TI  - Modelling the effects of temperature, water activity, pH and lactic acid
      concentration on the growth rate of Escherichia coli.
AB  - An extended square root-type model describing Escherichia coli growth rate was
      developed as a function of temperature (7.63-47.43 degrees C), water activity
      (0.951-0.999, adjusted with NaCl), pH (4.02-8.28) and lactic acid concentration
      (0-500 mM). The new model, based on 236 growth rate data, combines and extends
      previously published square root-type models and incorporates terms for upper and
      lower limiting temperatures, upper and lower limiting pH, minimum inhibitory
      concentrations of dissociated and undissociated lactic acid and lower limiting
      water activity. A term to describe upper limiting water activity was developed
      but could not be fitted to the E. coli data set because of the difficulty of
      generating data in the super-optimal water activity range (i.e. >0.998). All data
      used to generate the model are presented. The model provides an excellent
      description of the experimental data.

PMID- 12505459
TI  - Performance evaluation of a model describing the effects of temperature, water
      activity, pH and lactic acid concentration on the growth of Escherichia coli.
AB  - A square root-type model for Escherichia coli growth in response to temperature,
      water activity, pH and lactic acid was developed by Ross et al. [Int. J. Food
      Microbiol. (2002).]. Predicted generation times from the model were compared to
      the literature data using bias and accuracy factors, graphical comparisons and
      plots of residuals for data obtained from both liquid growth media and foods. The
      model predicted well for 1025 growth rate estimates reported in the literature
      after poor quality or unrepresentative data (n=215) was excluded, with a bias
      factor of 0.92, and an accuracy factor of 1.29. In a detailed comparison to two
      other predictive modes for E. coli growth, Pathogen Modeling Program (PMP) and
      Food MicroModel (FMM), the new model generally performed better. The new model
      consistently gave better predictions than the other models at generation times
      </=5 h. Inclusion of the lactic acid term in the model is proposed to account for
      the consistently good performance of the model for comparisons to growth in meat,
      a parameter that is not explicitly included in the other models considered in the
      comparisons.

PMID- 12505460
TI  - Bacterial composition of commercial probiotic products as evaluated by PCR-DGGE
      analysis.
AB  - The use of Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR
      DGGE) technique in identifying the microorganisms present in commercial probiotic
      yoghurts and lyophilised products was evaluated. Two reference ladders were
      assembled constituted by PCR-amplified V2-V3 regions of 16S rDNA from bacterial
      species generally used as probiotics. Identification was achieved comparing the
      PCR-DGGE patterns obtained from the analysed products with the ladder bands.
      Bands from members of the same species showed the same migration distance in
      denaturing gel, hence supporting the identificative value of the method. The
      validity of the technique was also proven confirming the PCR-DGGE identification
      results by sequence data analysis and by species-specific PCR. General congruence
      between microorganisms declared on the label and those revealed by PCR-DGGE was
      found for probiotic yoghurts. Conversely, some discrepancies were observed for
      probiotic lyophilised preparations, i.e. the incorrect identification of some
      Bifidobacterium and Bacillus species and the presence of not declared
      microorganisms. PCR-DGGE turned out to be an appropriate culture-independent
      approach for a rapid detection of the predominant species in mixed probiotic
      cultures.

PMID- 12505461
TI  - Influence of pH and temperature on growth of Bacillus cereus in vegetable
      substrates.
AB  - Bacillus cereus is a food-borne pathogen which most often contaminates foods of
      plant origin. Spores of psychrotrophic strains have the ability to germinate and
      grow at refrigeration temperatures in different vegetable substrates, such as
      carrot broth, zucchini broth, and cooked carrot puree. In some circumstances,
      factors such as pH, heat treatment, and storage temperature play a fundamental
      role in controlling the growth of these psychrotrophic strains and in extending
      the shelf life of refrigerated, minimally processed vegetable-based products in
      relation to pathogenic spore-forming bacteria. The combination of mild
      acidification (pH 5.0) and refrigeration (</=8 degrees C) inhibited B. cereus
      growth for at least 60 days in vegetable substrates similar to those mentioned
      above. This protection was maintained even when the temperature to which the food
      was exposed reached 12 degrees C. Psychrotrophic strains of B. cereus were
      inhibited in carrot broth by heating at 90 degrees C for 7.5 min, if the broth
      was refrigerated at a temperature of 8 degrees C or lower. If the vegetable
      product was exposed to temperatures of mild abuse (12 degrees C), it was
      necessary to implement a more drastic heat treatment (90 degrees C for 30 min).

PMID- 12505462
TI  - Evaluation of different methods for the detection of Clostridium perfringens
      phosphatases.
AB  - In order to detect phosphatase activity a total of 137 isolates from 12
      Clostridium (C.) species were examined via fluorescence on SCA-agar with
      methylumbelliferyl phosphate (SCA-MUP), via APIZYM and RAPID ID 32 A as well as
      using a phosphatase reagent containing 1-naphthyl phosphate. Fluorescence on SCA
      MUP showed the presence of acid or alkaline phosphatase in almost all isolates
      examined. Likewise, acid or alkaline phosphatase could be detected via APIZYM and
      RAPID ID 32 A in most strains and species. Opposed to this, the majority of the
      Clostridium bifermentans isolates showed a positive reaction exclusively on SCA
      MUP. On the other hand, the phosphatase reagent for the detection of acid
      phosphatase lead to unambiguously positive results only when examining
      Clostridium perfringens isolates. Therefore, the SCA-MUP-agar, in contrast to the
      phosphatase reagent, was proven to be unsuitable for the identification of C.
      perfringens via detection of acid phosphatase. Using the phosphatase reagent the
      activity of this enzyme was detected in 95.1% of the C. perfringens isolates
      included in the study. In addition, the phosphatase reagent showed identical
      reactions after a 24 h incubation at 37 degrees C and when used on cultures
      incubated for 6 h at 44 degrees C in the case of 98.5% of the C. perfringens
      isolates.

PMID- 12505463
TI  - A simple method for the differentiation of Listeria monocytogenes based on
      induction of lecithinase activity by charcoal.
AB  - The PlcB phospholipase C, or lecithinase, is an important listerial virulence
      factor of potential use as a pathogenicity marker for Listeria spp. food
      isolates. However, wild-type strains of Listeria monocytogenes express virulence
      factors very poorly in vitro and their lecithinase activity is normally difficult
      to detect on agar plates. We recently reported that the production of listerial
      virulence factors is strongly induced if L. monocytogenes is grown in the
      presence of activated charcoal. We report here a simple method for the rapid
      differentiation of L. monocytogenes from other Listeria spp. based on a
      comparison of lecithinase reactions in egg yolk agar plates with and without
      charcoal supplementation. All L. monocytogenes wild-type isolates tested showed a
      clear induction of lecithinase activity in charcoal-supplemented medium (CEYM),
      while nonpathogenic Listeria spp. remained negative in CEYM. The animal pathogen
      L. ivanovii was easily differentiated from L. monocytogenes because it showed a
      strong lecithinase reaction independently of the presence or absence of charcoal
      in the medium.

PMID- 12505464
TI  - Interpretations of the TDxFLx calibration data of the abused drugs.
AB  - The useful TDxFLx calibration data was obtained for the interpretation of the
      interactions of the abused drugs to sheep antiserum protein. The antibody of
      TDxFLx calibrators was prepared from sheep antiserum. Furthermore these data can
      be used to interpret the abused drug-protein binding phenomena in human body and
      the TDxFLx screening results of the abused drugs in urine samples. TDxFLx system
      uses fluorescence polarization immunoassay technique that is a competitive
      binding immunoassay methodology to allow tracer-labeled antigen (*Drug) and
      patient antigen (Drug) to compete for the same binding sites on the antibody
      molecules of sheep antiserum. To obtain the binding parameters, binding constant
      (K) and number of independent binding site (n), generally, Scatchard equation is
      used. This Scatchard equation is expressed in the concentration terms of free
      drug, bound drug, and protein (antibody). The binding parameters can not be
      obtained by applying the TDxFLx calibration data to the Scatchard equation
      directly because the TDxFLx calibration data are composed of the fluorescence
      polarization and the total drug concentrations. To obtain the binding parameters
      from the TDxFLx calibration data the new useful equation which was expressed in
      the total concentrations of drug and fluorescence polarization should be derived.
      Derivation of new equation was based on the Scatchard equation. The TDxFLx
      calibration data was curve fitted to the derived equation using KaleidaGraph
      program and Macintosh computer. The binding constant (K) and the number (n(P(t)))
      of binding site of 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid
      (COOH.THC) on the antibody were 1.14 x 10(8)l/mole and 4.04 x 10(-7)M,
      respectively. The binding constant and the number (n(P(t))) of binding site of
      amphetamine were 5.15 x 10(5)l/mole and 2.05 x 10(6)M, respectively. In case of
      COOH.THC the fluorescence polarization decreased linearly with the concentration.
      However, in case of amphetamine or the other three abused drugs the fluorescence
      polarizations decreased exponentially with their concentrations.

PMID- 12505465
TI  - Mast cell tryptase and hemolysis after trauma.
AB  - BACKGROUND: We have previously found increased mast cell tryptase in accidental
      deaths due to trauma, indicating that mast cell degranulation had occurred. The
      present study was designed to confirm the previous observation and to determine
      if tryptase release after trauma is acute or delayed. Furthermore, the importance
      of hemolysis and direct trauma to the mast cells was investigated. MATERIALS AND
      METHODS: Mast cell tryptase was measured in post-mortem blood from the femoral
      vein in 27 cases of death from trauma and in 27 control cases by means of a
      commercially available immunoassay. The trauma cases were further classified into
      groups with single versus multiple trauma, and groups with short survival time
      (i.e. death at the scene of the accident) versus longer survival time (death in
      hospital). In five multi-trauma deaths, blood was sampled locally from the sites
      of crush injury. RESULTS: The mean value of tryptase in femoral vein blood was
      35.6+/-34.6 microg/l in the entire trauma group and 14.7+/-6.5 microg/l in the
      controls (P<0.005). In bloody liquid sampled from crush injuries, tryptase was
      substantially elevated in all cases, with a mean of 227+/-146 microg/l. In cases
      with short survival time, tryptase was significantly higher than in those who
      died after several hours or days in hospital (P<0.001). No statistically
      significant difference was seen between multi- and single-trauma cases. A
      correlation between hemolysis in the samples and elevated tryptase was found only
      in the trauma cases (P<0.05), but experimentally induced hemolysis in vitro was
      not found to influence the measurements. CONCLUSION: Mast cell tryptase becomes
      elevated in trauma deaths and this seems to be ascribable either to direct
      mechanical injury to tissue mast cells and/or to cell lysis. In patients
      initially surviving severe injuries, the effects of massive release of histamine
      and other mast cell mediators might be of importance for treatment strategies and
      prognosis.

PMID- 12505466
TI  - Subdural haemorrhage sustained in a baby-rocker? A biomechanical approach to
      causation.
AB  - An unconscious 8 weeks old infant was admitted to hospital and found to have
      bilateral, subdural and retinal haemorrhages. He died the following day. The
      explanation for the subdural haemorrhage put forward by his carers was that the
      infant had been in a baby-rocker and that the carers had seen the rocker being
      rocked vigorously by their 14 months old daughter on two separate occasions. This
      paper describes the biomechanics of an infant model in the particular baby-rocker
      used and determines the maximum forces generated, comparing them with the
      'forces' thought to be compatible with the causation of subdural haemorrhage.

PMID- 12505467
TI  - The accuracy of three methods of age estimation using radiographic measurements
      of developing teeth.
AB  - The accuracy of age estimation using three quantitative methods of developing
      permanent teeth was investigated. These were Mornstad et al. [Scand. J. Dent.
      Res. 102 (1994) 137], Liversidge and Molleson [J. For. Sci. 44 (1999) 917] and
      Carels et al. [J. Biol. Bucc. 19 (1991) 297]. The sample consisted of 145 white
      Caucasian children (75 girls, 70 boys) aged between 8 and 13 years. Tooth length
      and apex width of mandibular canine, premolars and first and second molars were
      measured from orthopantomographs using a digitiser. These data were substituted
      into equations from the three methods and estimated age was calculated and
      compared to chronological age. Age was under-estimated in boys and girls using
      all the three methods; the mean difference between chronological and estimated
      ages for method I was -0.83 (standard deviation +/-0.96) years for boys and -0.67
      (+/-0.76) years for girls; method II -0.79 (+/-0.93) and -0.63 (+/-0.92); method
      III -1.03 (+/-1.48) and -1.35 (+/-1.11) for boys and girls, respectively. Further
      analysis of age cohorts, found the most accurate method to be method I for the
      age group 8.00-8.99 years where age could be predicted to 0.14+/-0.44 years
      (boys) and 0.10+/-0.32 years (girls). Accuracy was greater for younger children
      compared to older children and this decreased with age.

PMID- 12505468
TI  - Breath alcohol measurement variability associated with different instrumentation
      and protocols.
AB  - Breath alcohol measurement has variability resulting from instrumental,
      procedural and biological components. Reliable estimates of the standard
      deviation (S.D.) are necessary for calculating uncertainty in the form of
      confidence intervals. These estimates are concentration dependant and can be
      obtained from models derived from duplicate breath test data. Duplicate data from
      four state jurisdictions (Alabama using the Drager 7110, Minnesota using the
      Intoxilyzer 5000, Washington using the BAC Datamaster and Wisconsin using the
      Intoximeter EC/IR) were analyzed to derive predictive models for standard
      deviation as a function of concentration. All jurisdiction/instrument
      combinations yielded forensically acceptable variation while showing a general
      linear increase in standard deviation with concentration. This is consistent with
      a multiplicative error model. Jurisdictions using the same instruments but not
      performing duplicate analyses could also employ the straightforward models
      derived here to estimate standard deviations for their measurement results.

PMID- 12505469
TI  - Fatalities due to methyl alcohol intoxication in Turkey: an 8-year study.
AB  - The aim of this study is to examine methyl alcohol poisoning cases from the
      medico-legal point of view. The records of the Morgue Department of Council of
      the Forensic Medicine were reviewed retrospectively for all methyl alcohol
      poisonings for the period of 27.10.1992 and 30.05.2001. The victim's age, sex,
      death year, death place, methyl alcohol blood levels, the source of methyl
      alcohol, accompanying laboratory results and histopathologic tissue changes were
      recorded. The number of deaths due to the methyl alcohol poisoning was 271 during
      that period of time. Two hundred and forty-two of the (89.3%) total 271 methyl
      alcohol fatalities were men and 29 (10.7%) of were women. The largest age group
      was 36-40 years old, followed by 41-45. The methyl alcohol blood concentrations
      ranged widely from 50 to 755 mg for per 100 ml. There were 222 cases (81.9%) with
      the methyl alcohol blood concentrations over 100 mg/dl. Twenty-nine (10.7%)
      victims were poisoned through the consumption of cologne and three of them with
      alcoholic beverage named "Raki". Consumed products were not known in all other
      cases because of insufficient patient history and data. As a conclusion,
      regarding the distribution according to years, mortality due to methyl alcohol
      intoxication in our country have been proceeding on a certain level. In order to
      decrease the mortality due to methyl alcohol intoxication, some precautions
      should be developed that could prevent the production and consumption of
      alcoholic beverages illegally produced.

PMID- 12505470
TI  - Testing the utility of a geographical profiling approach in three rape series of
      a single offender: a case study.
AB  - The purpose of the study was to test the potential utility of a geographical
      profiling approach for three separate series of rapes committed by a single
      offender. Two different mathematical distance-decay functions using either a
      normal distribution with a mean distance and standard deviation based on previous
      research or a truncated negative exponential function based on distances between
      crime sites in the series under investigation were applied to each of the series
      giving prioritised search areas the accuracy of which was then assessed. The
      prioritised area that had to be searched before the home base of the offender
      could be located varied from 7.60 km(2) or 2.15% of the total search area at its
      best to 15 1.10 km(2) or 42.66% at its worst for the normal distribution based on
      previous research and from 42.06 km(2) or 11.88% to no improvement when the
      truncated negative exponential function was used. The functions used showed less
      predictive ability when the offender was a commuter. Explanations for the
      variations in the findings as well as suggestions for improvements were outlined
      in the discussion.

PMID- 12505471
TI  - A highly polymorphic STR locus in Cannabis sativa.
AB  - We report on the first short tandem repeat (STR) locus to be isolated from the
      plant Cannabis sativa. The STR locus, isolated by a hybrid-capture enrichment
      procedure, was found to contain a simple sequence repeat motif of 6 bp. This 6 bp
      repeat motif showed no variation in repeat length but with minor variations in
      repeat unit sequences. The data show the locus to be highly polymorphic with the
      number of repeat units ranging from 3 to 40 in 108 screened samples. The observed
      heterozygosity was approximately 87.04%. The forward and reverse primers (CS1F
      and CS1R) produced no PCR products in cross-reaction study from 20 species of
      plants, including highly related species such as Humulus japonicus and Nicotiana
      tabacum. This hexanucleotide repeat DNA locus could be used to identify cannabis
      samples and predict their genetic relationship as the test is specific to C.
      sativa and is highly reproducible.

PMID- 12505472
TI  - "Ancient" protocols for the crime scene? Similarities and differences between
      forensic genetics and ancient DNA analysis.
AB  - We provide a short overview on some current issues in the fields of forensic
      genetics and ancient DNA (aDNA) analysis. We discuss about the existence of the
      possible points of contact between the two disciplines, in terms of open problems
      and the inherent approach to their solution. We mainly focus on the problem of
      results authentication, its theoretical and technical aspects.

PMID- 12505473
TI  - Short tandem repeat (STR) DNA markers are hypervariable and informative in
      Cannabis sativa: implications for forensic investigations.
AB  - Short tandem repeat (STR) markers are the DNA marker of choice in forensic
      analysis of human DNA. Here we extend the application of STR markers to Cannabis
      sativa and demonstrate their potential for forensic investigations. Ninety-three
      individual cannabis plants, representing drug and fibre accessions of widespread
      origin were profiled with five STR makers. A total of 79 alleles were detected
      across the five loci. All but four individuals from a single drug-type accession
      had a unique multilocus genotype. An analysis of molecular variance (AMOVA)
      revealed significant genetic variation among accessions, with an average of 25%
      genetic differentiation. By contrast, only 6% genetic difference was detected
      between drug and fibre crop accessions and it was not possible to unequivocally
      assign plants as either drug or fibre type. However, our results suggest that
      drug strains may typically possess lower genetic diversity than fibre strains,
      which may ultimately provide a means of genetic delineation. Our findings
      demonstrate the promise of cannabis STR markers to provide information on: (1)
      agronomic type, (2) the geographical origin of drug seizures, and (3) evidence of
      conspiracy in production of clonally propagated drug crops.

PMID- 12505474
TI  - Application of species-specific polymerase chain reaction in the forensic
      identification of tiger species.
AB  - Globally, tigers are considered to be endangered, and are listed on Appendix I of
      CITES. A simple test, using a species-specific primer pair, was developed to
      identify tiger meat, faeces and dried skin, and provide forensic evidence of
      illegal wildlife trade. The specific fragment of mitochondrial cytochrome b gene
      was also successfully amplified from raw DNA products extracted from single tiger
      hairs. This PCR-based approach opens a new avenue to forensic identification of
      less-than-optimal samples.

PMID- 12505476
TI  - Cerebral haemodynamics in obstructive sleep apnoea and Cheyne-Stokes respiration.
AB  - Obstructive sleep apnoeas are common among stroke patients and, as different from
      central apnoeas, they do not decline during stroke rehabilitation. Cerebral and
      cardiovascular changes display a different pattern during central and obstructive
      sleep apnoeas. The cerebral blood flow velocity according to transcranial Doppler
      increases during an obstructive apnoea and decreases after apnoea termination
      concomitant with changes in arterial pressure. The changes in cerebral
      circulation during obstructive apnoeas could be an immediate effect of rapid
      changes in blood pressure because cerebral autoregulation is overridden. Low
      cerebral blood flow, low arterial pressure and hypoxemia after apnoea termination
      may predispose to nocturnal cerebral ischaemia. The opposite pattern is seen
      during a central apnoea, with a decrease in cerebral blood flow velocity during
      apnoea and an increase after apnoea termination. Changes during obstructive
      apnoeas are probably hazardous, with adverse cardiovascular effects including
      stroke. This may not be the case during central apnoeas, as Cheyne-Stokes
      respiration with central apnoeas is a result of an underlying disorder such as
      heart failure and stroke and is not a disease entity in itself. It is suggested
      that obstructive sleep apnoea is a risk factor for stroke as it is common among
      stroke victims and cerebral hypoperfusion occurs after an obstructive apnoea. The
      treatment of sleep apnoea should also be taken into account among stroke
      patients. Large cohort studies, treatment studies and further studies of possible
      mechanisms for apnoea-induced stroke are, however, essential in order to evaluate
      whether obstructive sleep apnoea is an independent risk factor for stroke.

PMID- 12505477
TI  - The cerebral circulation during sleep: regulation mechanisms and functional
      implications.
AB  - Cerebral blood flow measurements during sleep are reviewed and discussed in
      relation to the different techniques utilized (Positron Emission Tomography,
      functional Magnetic Resonance Imaging, Flowmeters, Radioactive MicroIspheres,
      Brain Temperature Recordings, Spectrophotometry) since these methodological
      approaches aim at diverse features of circulation changes in the spatial or
      temporal domain. The regulation of cerebral circulation during sleep reveals no
      specific state-dependent features, flow-activity coupling being the prevailing
      mechanism, with O(2) as the primary candidate for the metabolic side of the link.
      On a general level, the latest data on brain circulation are compatible with the
      classical hypothesis of a "restorative" function of sleep processes.

PMID- 12505478
TI  - Stroke and sleep apnoea: cause or consequence?
AB  - The relationships between obstructive sleep apnoea syndrome (OSAS) and stroke are
      still under discussion, but increasing evidence demonstrates that the OSAS is an
      independent risk factor for stroke. However, in rare cases, OSAS could be a
      consequence of strokes, especially if located in the brainstem. Many recent
      studies have found a 70 to 95% frequency of OSAS (defined by an apnoea/hypopnoea
      index >10) in patients with acute stroke. Age, body mass index, diabetes, and
      severity of stroke have been identified as independent predictors of stroke.
      Furthermore, the presence of OSAS in stroke patients could lead to a poor
      outcome. The potential mechanisms linking OSAS and stroke are probably multiple
      (arterial hypertension, cardiac arrhythmia, increased atherogenesis, coagulation
      disorders, and cerebral haemodynamic changes). Despite numerous uncertainties,
      OSAS should be systematically screened at the moment it is clinically suspected
      in patients with acute stroke. However, the optimal timing (early or differed)
      for treatment with nasal continuous positive airway pressure remains to be
      determined.

PMID- 12505479
TI  - Sleep and headache.
AB  - The relationship between sleep and headache has been known for over a century.
      Headache and sleeping problems are both some of the most commonly reported
      problems in clinical practice, and cause considerable social and family problems,
      as well as socio-economic impact and costs. There is a clear association between
      headache and sleep disturbances, especially headaches occurring during the night
      or early morning. The mechanism and causes are complex, multifactorial and poorly
      understood. Headache disorders like migraine, tension-type headache, cluster
      headache and hypnic headache all affect or are directly related to sleep
      disturbances and daytime functioning. Sleep fragmentation, insomnia and
      hypersomnia all show relations to headache. Primary sleep disorders like
      insomnia, hypersomnias including sleep disordered breathing are all associated
      with and may cause headache. Furthermore medical, psychiatric and rheumatic
      diseases are associated with sleep disturbances and headache. The current
      knowledge about headache and sleep is still sparse and further research is
      advocated.

PMID- 12505480
TI  - The interaction between sleep and thermoregulation in adults and neonates.
AB  - The interaction between sleep and thermoregulation leads to different
      thermoregulatory responses depending on the sleep stage and alterations in sleep
      when in a cool or warm environment. In the human adult, differences in
      thermoregulatory efficiency during rapid eye movement (REM) sleep and slow wave
      sleep (SWS) are less pronounced compared to other mammals: although
      thermoregulatory processes persist in REM sleep, they are less efficient than
      during SWS. Cold and warm loads disturb the efficiency and structure of sleep.
      The duration of REM sleep and (to a lesser extent) of SWS decreases. In contrast,
      pre-sleep warm loads enhance SWS and improve sleep continuity. This procedure may
      promote and maintain sleep in depressed patients, whose sleep and body
      temperature rhythms are modified. In contrast to adults, homeothermic processes
      in neonates are maintained or even enhanced during active sleep (AS) when
      compared to quiet sleep (QS). Sleeping in a cool environment increases the
      duration of AS at the expense of QS. As a result, the thermoregulatory function
      overcomes the need to conserve energy that would otherwise lead to increased QS.
      An interaction between sleep, respiration, and thermoregulation may be involved
      in Sudden Infant Death Syndrome: an alteration in the thermal balance may perhaps
      induce respiration instability, especially during AS.

PMID- 12505481
TI  - Correlation between radiographic severity of knee osteoarthritis and future
      disease progression. Results from a 3-year prospective, placebo-controlled study
      evaluating the effect of glucosamine sulfate.
AB  - OBJECTIVE: To investigate the relationship between baseline radiographic severity
      of knee osteoarthritis (OA) and the importance of long-term joint space
      narrowing. DESIGN: Sub-analysis from a three-year randomized, placebo-controlled,
      prospective study, of 212 patients with knee OA, recruited in an osteoarthritic
      outpatient clinic and having been part of a study evaluating the effect of
      glucosamine sulfate on symptom and structure modification in knee OA. MATERIAL
      AND METHODS: Measurements of mean joint space width (JSW), assessed by a computer
      assisted method, were performed at baseline and after 3 years, on weightbearing
      anteroposterior knee radiographs. RESULTS: In the placebo group, baseline JSW was
      significantly and negatively correlated with the joint space narrowing observed
      after 3 years (r=-0.34, P=0.003). In the lowest quartile of baseline mean JSW
      (<4.5mm), the JSW increased after 3 years by (mean (S.D.)) 3.8% (23.8) in the
      placebo group and 6.2% (17.5) in the glucosamine sulfate group. The difference
      between the two groups in these patients with the most severe OA at baseline was
      not statistically significant (P=0.70). In the highest quartile of baseline mean
      JSW (>6.2mm), a joint space narrowing of 14.9% (17.9) occurred in the placebo
      group after 3 years while patients from the glucosamine sulfate group only
      experienced a narrowing of 6.0% (15.1). Patients with the most severe OA at
      baseline had a RR of 0.42 (0.17-1.01) to experience a 0.5mm joint space narrowing
      over 3 years, compared to those with the less affected joint. In patients with
      mild OA, i.e. in the highest quartile of baseline mean JSW, glucosamine sulfate
      use was associated with a trend (P=0.10) towards a significant reduction in joint
      space narrowing. CONCLUSION: These results suggest that patients with the less
      severe radiographic knee OA will experience, over 3 years, the most dramatic
      disease progression in terms of joint space narrowing. Such patients may be
      particularly responsive to structure-modifying drugs.

PMID- 12505482
TI  - Runx2 expression and action in chondrocytes are regulated by retinoid signaling
      and parathyroid hormone-related peptide (PTHrP).
AB  - OBJECTIVE: Runx2 (also known as Cbfa1) is a transcription factor required for
      chondrocyte maturation and osteoblast differentiation. While there is information
      on the regulation of its expression during osteogenesis, much less is known about
      it during cartilage maturation. Here we asked whether Runx2 expression and
      function are affected by retinoic acid (RA) and parathyroid hormone-related
      peptide (PTHrP), which represent an important stimulator and inhibitor of
      chondrocyte maturation, respectively. DESIGN: We first cloned and characterized
      Runx2 expressed by chick chondrocytes (cRunx2). We then constructed expression
      vectors of cRunx2 and a dominant-negative form (DN-cRunx2) and determined their
      effects on chondrocyte maturation in culture before and during retinoid and PTHrP
      treatment. RESULTS: cRunx2 showed similar transactivation activity to that of its
      mammalian counterparts although it has a very short QA domain and lacks a small
      portion of the PST domain. cRunx2 over-expression stimulated chondrocyte
      maturation, as indicated by increases in alkaline phosphatase activity (APase),
      mineralization, and type X collagen and MMP-13 expression, and by maintenance of
      Indian hedgehog (Ihh) expression. RA treatment stimulated cRunx2 gene expression
      and boosted its pro-maturation effects. PTHrP treatment blocked Runx2 expression
      and its pro-maturation effects. Over-expression of DN-cRunx2 inhibited maturation
      and even prevented RA from exerting its pro-maturation role. CONCLUSIONS: As
      previously indicated by mammalian studies, cRunx2 has chondrocyte pro-maturation
      activity. Its expression and roles are favorably modulated by retinoid signaling
      but are completely inhibited by PTHrP. A model integrating cRunx2 with PTHrP, Ihh
      and retinoid signaling and operating during skeletogenesis is proposed.

PMID- 12505483
TI  - Cartilage repair using new polysaccharidic biomaterials: macroscopic,
      histological and biochemical approaches in a rat model of cartilage defect.
AB  - OBJECTIVE: The present study aims at evaluating, in a rat model of cartilage
      defect, the potential of various polymers as filling and repair biomaterials. The
      macroscopic and histological observations are compared to biochemical parameters
      in order to appreciate the pertinence of the latter as suitable criteria in
      tissue engineering. METHODS: A hydrogel, consisting of hyaluronic acid (HA),
      covalently substituted by hydrophobic alkyl chains (HA12, HA18) and an alginate
      sponge, alone (Asp) or combined with HA (AHAsp) or combined with HA and
      chondrocytes (HYBsp) were evaluated. Cartilage lesions were drilled in femoral
      trochlea of rats. The analyses were performed on trochlea as well as on patella
      and condyles. RESULTS: Repairs achieved with hydrogels had a similar macroscopic
      appearance than those afforded by AHAsp and HYBsp. Best macroscopic and
      histological scores were obtained with HA18 and HYBsp in comparison with alginate
      group (P< 0.01 and P< 0.02 respectively). Biochemical evaluations confirmed the
      presence of similar amounts of proteoglycans in the repaired zones and in the
      controls, though with different DeltadiC4S/DeltadiC6S ratios and enhanced HA
      levels. CONCLUSIONS: Hydrogels or sponges proved to be colonized by cells
      synthesizing a matrix with a high HA content. The matrix obtained eventually
      turns hyaline and takes over the scaffold. The addition of HA and/or chondrocytes
      to Asp significantly improves the macroscopic and histological scores (P< 0.05
      and P< 0.02 respectively). However, biochemical parameters are significantly
      different of those evaluated in native cartilage. The present study shows that
      only biochemical parameters allow to discriminate between various biomaterials in
      tissue engineering and are essential informations which should be taken into
      account in addition to macroscopic and histological observations.

PMID- 12505484
TI  - Smoking and osteoarthritis: is there an association? The Clearwater
      Osteoarthritis Study.
AB  - OBJECTIVE: To evaluate the association between cigarette smoking and the
      subsequent development of osteoarthritis (OA) at four separate sites: knee, hand,
      foot and cervical spine. METHODS: This cohort study examined 2505 men and women
      aged 40 years and older participating in the longitudinal Clearwater
      Osteoarthritis Study (1988-current). Biennial physical exams, including serial
      radiographs, as well as historical information, were collected. The Lawrence and
      Kellgren ordinal scale was used to determine radiological evidence of the study
      outcome, OA. Self-reported history of smoking behavior was used to determine the
      study exposure. Smoking was classified using four approaches: (1) ever/never, (2)
      former/never, (3) current/never, and (4) dose. RESULTS: Among the individuals at
      study entry, radiologically confirmed incident OA was detected during the follow
      up period at four sites: knee (32%), hand (49%), foot (28%), and cervical spine
      (52%). Approximately 11% were self-reported current smokers. Unadjusted analyses
      indicated that individuals classified as current smokers demonstrated significant
      levels of protection from OA at all four sites investigated. However, adjusted
      point estimates ranging from 0.60-1.48 were suggestive of no association between
      smoking and the development of OA at any of the four sites investigated.
      CONCLUSION: Based upon the findings of this prospective study, smoking does not
      appear to convey a clinically significant level of protection against the
      development of radiologically-confirmed OA. While these findings corroborate
      previous studies indicating no association between smoking and OA, anecdotal
      evidence warrants investigation into the role that cigarette smoking may play in
      the symptomatology of OA.

PMID- 12505485
TI  - Activation of beta-catenin-LEF/TCF signal pathway in chondrocytes stimulates
      ectopic endochondral ossification.
AB  - OBJECTIVE: Members of the Wnt signaling protein family are expressed during
      cartilage development and skeletogenesis, but their roles and mechanisms of
      action in those processes remain unclear. Recently, we found that beta-catenin
      LEF/TCF-dependent Wnt signaling stimulates chondrocyte maturation and hypertrophy
      and extracellular matrix calcification in vitro, events normally associated with
      cartilage-to-bone transition during skeletogenesis. Thus, we tested here whether
      activation of this pathway promotes endochondral ossification. DESIGN: Chick
      chondrocytes were infected with avian retroviral expression vectors encoding
      constitutive-active (CA) or dominant-negative (DN) forms of LEF, which activate
      or block beta-catenin-dependent Wnt signaling respectively. These cells and
      companion uninfected control cells were seeded into type I collagen gels and
      transplanted intramuscularly into nude mice. The resulting ectopic tissue masses
      forming over time in vivo were subjected to histological and molecular biological
      analyses. RESULTS: Transplantation of chick chondrocytes induced de novo
      endochondral bone formation. In situ hybridization and RT-PCR using species
      specific probes and primers showed that the ectopic cartilaginous tissue was
      avian and thus donor-derived, whereas the bone tissue was mouse and thus host
      derived. CA-LEF-expressing ectopic tissue masses contained abundant bone and
      marrow, while DN-LEF-expressing masses contained little bone and lacked marrow.
      CONCLUSIONS: Activation of beta-catenin-LEF/TCF-dependent Wnt signaling
      accelerates chondrocyte maturation and replacement of cartilage by bone.

PMID- 12505486
TI  - The effects of hyaluronic acid on fibronectin fragment mediated cartilage
      chondrolysis in skeletally mature rabbits.
AB  - OBJECTIVE: Intraarticular Na-Hyaluronate (HA) exerts a beneficial effect on
      adolescent rabbits after fibronectin fragment (Fn-f) mediated cartilage injury.
      We extended our studies to a population of rabbits which have reached full
      skeletal maturity. DESIGN: Adult male NZW rabbits received an injury with Fn-f
      and no further treatment; an injection of HA followed by Fn-f injury, or Fn-f
      injury followed by a single or weekly intraarticular injection of HA. All animals
      were sacrificed 38 days after receiving the Fn-f injury. After sacrifice,
      proteoglycan (PG) content was determined from articular cartilage from the medial
      femoral condyles and tibial plateaus. The patellae were processed for histology.
      RESULTS: Cartilage PG contents were significantly reduced after Fn-f injection
      (P=0.0167) and were only slightly improved with HA pre-treatment. However, post
      treatment with HA resulted in significant improvements in cartilage PG content
      when compared to Fn-f only (single HA, P=0.01; weekly HA,P =0.01). Loss of
      Safranin-O staining, cell loss, osteophyte formation and inflammation were
      present in the patellae following Fn-f injection. Pre-treatment with HA reduced
      these changes. More significant protection of cartilage and restoration of Fn-f
      injury were noted in animals receiving post-treatment with HA. CONCLUSIONS: These
      results suggest that 38 days after Fn-f injury the lost PG content induced by Fn
      f injection is substantially restored by weekly post-treatment with
      intraarticular HA in rabbits that have reached full skeletal maturity.

PMID- 12505487
TI  - Synovial fluid features and their relations to osteoarthritis severity: new
      findings from sequential studies.
AB  - OBJECTIVE: Many factors are involved in the osteoarthritic process. It is not yet
      known which are initiators, promoters or simply results. Thus, we have evaluated
      some of those potentially important factors in osteoarthritis (OA) as observed
      sequentially for the first time in synovial fluids. DESIGN: Synovial fluids (SF)
      obtained between 1992-2002 were all routinely evaluated for gross appearance,
      leukocyte counts and microscopic examination of wet drop preparations. We used
      regular and polarized light and alizarin red s stains. We separated out all OA
      patients, then we looked for patients who had more than two synovial fluid
      analyses to get sequential information. Time between first and final aspiration
      ranged from 2 to 7 (3.6+/-1.6) years and number of analyses per patients from 3
      to 6 (3.3+/-0.7). We related synovial fluid crystals, fibrils and white blood
      cell count (WBC) to age, sex, disease duration and radiographic assessment
      according to the Kellgren-Lawrence radiographic rating system. RESULTS: Of 4523
      synovial fluid examinations, we found 855 in patients with knee OA; 330 patients
      with adequate clinical details for comparison were included in our study. Twenty
      six patients (one woman and 25 men) had sequentially examined SF. We found that
      52% of those OA patients with effusions studied had crystals identified in their
      synovial fluid. Twenty-one percent of all the patients had CPPD crystals, 47% had
      hydroxyapatite, also called basic calcium phosphate (BCP) crystals and 16% had
      both types of crystals. Microscopically identifiable fibrils were found in 60% of
      SF. In sequentially examined patients, CPPD crystals and apatite (BCP) were found
      in 19% and 23%, respectively, at the first aspiration and, in 34% and 58% at the
      final aspiration. Fibrils were seen in 54% at first examination and 85% later.
      Apatite and fibrils showed more significant correlation with time (r=0.51,r
      =0.92) than did CPPD (r=0.32). SF WBC correlated only with CPPD crystals and did
      not increase with OA duration or severity. CPPD, apatite and fibrils all
      correlated with higher radiographic grades of OA. CONCLUSIONS: As noted before
      CPPD and apatite crystals were more common in patients with more severe OA. New
      findings are that our sequential cases showed that there were some patients with
      no crystals at onset but that crystals appeared with progression of the disease.
      Fibril presence in SF also correlated with progression of the disease.

PMID- 12505488
TI  - Combined effects of insulin-like growth factor-1 and transforming growth factor
      beta1 on periosteal mesenchymal cells during chondrogenesis in vitro.
AB  - OBJECTIVE: Periosteum contains undifferentiated mesenchymal stem cells that have
      both chondrogenic and osteogenic potential, and has been used to repair articular
      cartilage defects. During this process, the role of growth factors that stimulate
      the periosteal mesenchymal cells toward chondrogenesis to regenerate articular
      cartilage and maintain its phenotype is not yet fully understood. In this study,
      we examined the effects of insulin-like growth factor-1 (IGF-1) and transforming
      growth factor-beta1 (TGF-beta1), alone and in combination, on periosteal
      chondrogenesis using an in vitro organ culture model. METHODS: Periosteal
      explants from the medial proximal tibia of 2-month-old rabbits were cultured in
      agarose under serum free conditions for up to 6 weeks. After culture the explants
      were weighed, assayed for cartilage production via Safranin O staining and
      histomorphometry, assessed for proliferation via proliferative cell nuclear
      antigen (PCNA) immunostaining, and assessed for type II collagen mRNA expression
      via in situ hybridization. RESULTS: IGF-1 significantly increased chondrogenesis
      in a dose-dependent manner when administered continuously throughout the culture
      period. Continuous IGF-1, in combination with TGF-beta1 for the first 2 days,
      further enhanced overall total cartilage growth. Immunohistochemistry for PCNA
      revealed that combining IGF-1 with TGF-beta1 gave the strongest proliferative
      stimulus early during chondrogenesis. In situ hybridization for type II collagen
      showed that continuous IGF-1 maintained type II collagen mRNA expression
      throughout the cambium layer from 2 to 6 weeks. CONCLUSION: The results of this
      study demonstrate that IGF-1 and TGF-beta1 can act in combination to regulate
      proliferation and differentiation of periosteal mesenchymal cells during
      chondrogenesis.

PMID- 12505489
TI  - Topographical analysis of the structural, biochemical and dynamic biomechanical
      properties of cartilage in an ovine model of osteoarthritis.
AB  - OBJECTIVE: The relationship between the topographical variations in the
      structural, biochemical and dynamic biomechanical properties of articular
      cartilage (AC) before and 6 months after meniscectomy has not been previously
      reported but is clearly relevant to our understanding of the role of mechanical
      factors on the pathogenesis of osteoarthritis (OA). The objective of this study
      was to address this deficiency using an ovine model of OA induced by bilateral
      lateral meniscectomy. DESIGN: The dynamic effective shear modulus (G*) and phase
      lag were determined ex vivo at 26 individual locations over the medial and
      lateral tibial plateaux of non-operated and meniscectomized ovine joints 6 months
      after surgery using a novel hand-held dynamic indentation probe. AC thickness was
      measured with a needle penetration probe. The AC from the same topographical
      locations as indented was then analysed for sulfated glycosaminoglycans (S-GAG)
      as a measure of proteoglycan (PG) levels, collagen and water content.
      Histological evaluation of the collagen organization using quantitative analysis
      of birefringence intensity was performed on stained tissue sections from the same
      topographical locations of each animal. RESULTS: It was demonstrated that the AC
      of the entire lateral tibial compartment of the meniscectomized joints underwent
      significant local degenerative and compensatory changes as indicated by a
      decreased G* and an increase in phase lag and water content. This was accompanied
      by a decrease in PG content of the AC of the middle and inner regions. While the
      AC of the outer region of the lateral meniscectomized compartment showed a marked
      increase in PG content and a more than two-fold increase in thickness, these
      tissues were also found to be structurally inferior, as indicated by a decreased
      G* and abnormal collagen birefringence intensity. The AC thickness was elevated
      at all locations of the lateral and medial tibial plateau of the meniscectomized
      joints. Strong and significant correlations between the biomechanical and
      biochemical data were established for a number of the parameters examined,
      especially between collagen content and G*, collagen content and AC thickness,
      and G* and AC thickness. An inverse correlation between S-GAG content and G* was
      only apparent in non-operated control tissues, whereas correlations between
      collagen and water content, water content and G*, and water content and thickness
      were evident for AC of the meniscectomized tibial plateaux. Less striking changes
      were noted in the medial compartment where the intact meniscus remained in place.
      However, elevated PG content, thicker AC together with slight changes in G*
      suggested an early hypertrophic response in these tissues. CONCLUSION: This study
      has highlighted the variable response of AC in different topographical regions of
      meniscectomized joints to the altered mechanical stresses introduced by this
      surgical procedure. The AC at the joint margins, while thicker and richer in PG,
      was found to be biomechanically softer (lower shear modulus) than normal AC, and
      because of this, would be expected to undergo degenerative changes with time
      leading to the onset of OA.

PMID- 12505490
TI  - Presence and mechanism of knee articular cartilage degeneration after meniscal
      reconstruction in dogs.
AB  - OBJECTIVE: Partial meniscectomy is the golden standard for treating a bucket
      handle tear in the meniscus of the knee, but it inevitably leads to articular
      cartilage degeneration. Surgical creation of an access channel between the lesion
      and the vascularized synovial lining is intended to induce ingrowth of repair
      tissue and thus avoid degeneration of articular cartilage. DESIGN: The presence
      and mechanism of cartilage degeneration were evaluated in 24 canine menisci after
      a longitudinal lesion and access channel had been created in the avascular part
      of the meniscus. In 12 menisci the channel was implanted with a porous polymer
      scaffold, while the remaining 12 were left empty. Evaluation was performed using
      routine histology and antibodies directed against denatured type II collagen
      (Col2-3/4M). RESULTS: Articular degeneration was apparent in the polymer implant
      group and the empty channel group. This consisted of fibrillation, loss of
      chondrocytes and decreased proteoglycan content. Areas of fibrillated cartilage
      always showed positive labeling with the collagen degradation antibody Col2-3/4M.
      Collagen degradation was also visible in non-fibrillated areas. The upper zone of
      the cartilage showed swelling especially in the implant group, with empty cell
      lacunae and moderate levels of Col2-3/4M antibody labeling. DISCUSSION: This
      reconstruction technique cannot be considered superior to partial meniscectomy.
      We propose that degradation of the collagen type II network is a result of
      cartilage fibrillation and vice versa.

PMID- 12505509
TI  - Aggregation and dispersion characteristics of calcium oxalate monohydrate: effect
      of urinary species.
AB  - In this research, screening and central composite experimental designs are used
      to determine the effect of various factors on the aggregation and dispersion
      characteristics of previously grown calcium oxalate monohydrate (COM) crystals in
      artificial urinary environments of controlled variables. The variables examined
      are pH and calcium, oxalate, pyrophosphate, citrate, and protein concentrations
      in ultrapure water and artificial urine. Optical density measurements, particle
      size analysis, optical microscopy, AFM force measurements, and protein adsorption
      have been used to assess the state of aggregation and dispersion of the COM
      crystals and to elucidate the mechanisms involved in such a complex system. The
      data indicate that our model protein, mucin, acts as a dispersant. This is
      attributed to steric hindrance resulting from the adsorbed mucoprotein. Oxalate,
      however, promotes aggregation. Interesting interactions between protein and
      oxalate along with protein and citrate are observed. Such interactions
      (synergistic or antagonistic) are found to depend on the concentrations of these
      species. Surface responses for these interactions are presented and discussed in
      this paper. In summary, solution, surface, and interface chemistries interact in
      a complex manner in the physiological environment to either inhibit or promote
      aggregation, and an understanding of such interactions may help determine and
      control the factors affecting kidney stone formation.

PMID- 12505514
TI  - Effect of degree, type, and position of unsaturation on the pKa of long-chain
      fatty acids.
AB  - Titration of a series of C(18) fatty acids yields pK(a) values that decrease with
      an increasing degree of unsaturation in the fatty acid chain. The pK(a) values of
      stearic, elaidic, oleic, linoleic, and linolenic acids were studied and compared
      to values of area per molecule in a spread monolayer of these acids. The decrease
      in pK(a) was found to relate to melting point temperature and area per molecule
      in the spread fatty acid monolayer. The pK(a) value was determined by first
      dissolving the fatty acid in a high pH solution (pH>10) and subsequently
      titrating the solution with HCl to obtain the characteristic S-shaped curves used
      to calculate the pK(a) values. The pK(a) values of stearic, elaidic, oleic,
      linoleic, and linolenic acids were found to be 10.15, 9.95, 9.85, 9.24, and 8.28,
      respectively. These pK(a) values were in the same order as area per molecule
      values of fatty acids in spread monolayers. This suggests that as area per
      molecule increases the intermolecular distance increases and pK(a) decreases due
      to reduced cooperation between adjacent carboxyl groups.

PMID- 12505515
TI  - Some aspects of stability of multiple emulsions in personal cleansing systems.
AB  - The two dominant factors that were found to affect the stability of multiple
      emulsions in high HLB surfactant systems are the osmotic pressure imbalance
      between the internal aqueous phase and the external aqueous phase, and the
      adsorption/desorption characteristics of the emulsifier/surfactant film at the
      oil/water interface. Synergistic interaction between the low HLB emulsifier and
      the high HLB surfactant that produces very low interfacial tension of the order
      of 10(-2) mN/m at the oil/water interface was found to occur in some of the
      systems investigated. Long term stability was observed in multiple emulsion
      containing these systems. However, no synergy was observed in systems in which
      either the oil or the emulsifier, or both, contained unsaturated chains. In fact,
      desorption of the adsorbed surfactant film was observed in systems containing
      unsaturated chains. The observed desorption from the interface of the emulsifier
      in these systems was attributed mainly to the inability of the unsaturated chains
      to form a close packed, condensed interfacial film. Presence of closely packed,
      condensed interfacial film is necessary to prevent solubilization of the adsorbed
      low HLB emulsifier by the high HLB surfactant. Multiple emulsions prepared using
      systems containing unsaturated hydrocarbons were highly unstable.

PMID- 12505520
TI  - Dynamics of Ly49 expressing cytotoxic lymphocyte subsets in response to virus
      infection.
AB  - Viral infections induce first a loss and then an increase in natural killer (NK)
      and CD8(+) T cells. NK cells expressing Ly49G2 were selectively expanded by
      several viruses and poly I:C. CD8(+) T cells expressing Ly49G2 were selectively
      expanded by poly I:C and participated in the antigen-specific response to
      lymphocytic choriomeningitis virus.

PMID- 12505521
TI  - Innate immunity to cytomegalovirus: the Cmv1 locus and its role in natural killer
      cell function.
AB  - The identification and characterization of genetic loci that contribute to
      patterns of susceptibility/resistance to infection provide important insights
      into the mechanisms of innate and adaptive immunity. Genetic heterogeneity across
      the population makes the characterization of such traits in humans technically
      difficult; however, inbred animal models represent an ideal tool for such
      analyses. This review illustrates the power of mouse genetics as utilized for the
      identification and characterization of the locus conferring early resistance to
      murine cytomegalovirus infection, Cmv1. This locus encodes an activating C-type
      lectin receptor of the Ly49 family that promotes natural killer (NK) cell
      cytolysis of infected cells. Although NK cells are usually able to detect and
      destroy virally infected cells via recognition of the downregulation of MHC class
      I molecules, the Cmv1 locus provides the first example of an NK receptor that is
      able to mediate clearance of viral infection via direct recognition of a virally
      encoded protein.

PMID- 12505522
TI  - Virus-driven evolution of natural killer cell receptors.
AB  - Natural killer (NK) cells can mount an immediate response against viral
      infection, secreting cytokines and killing virus-infected cells. However, viruses
      have devised strategies to avoid immune detection. Here, we discuss NK cell
      recognition of viruses and propose that viruses may provide the evolutionary
      pressure causing the diversification of the NK cell receptors.

PMID- 12505523
TI  - Natural killer cell activation receptors in innate immunity to infection.
AB  - Natural killer (NK) cells are best known for their capacity to kill tumors but
      they are also critical in early innate responses to infection, especially
      herpesviruses. Recent studies indicate that NK cell receptors involved in tumor
      target specificity are also involved in responses to viral infections.

PMID- 12505524
TI  - NK cell receptors: emerging roles in host defense against infectious agents.
AB  - Natural killer (NK) cells have the ability to become activated under the
      appropriate conditions by utilizing one or more cell surface receptors that are
      capable of inducing NK cell cytokine production and/or cytotoxicity. The
      expression of a variable array of inhibitory receptors on the surface of NK cells
      acts to counterbalance the positive signals initiated through activating
      receptors. Increasing evidence suggests an important role for both activating and
      inhibitory NK cell receptors in an appropriate and controlled NK response to
      infectious agents.

PMID- 12505525
TI  - Regulatory pathways involved in the infection-induced production of IFN-gamma by
      NK cells.
AB  - The production of interferon gamma (IFN-gamma) by natural killer (NK) cells
      provides an innate mechanism of resistance to many intracellular pathogens. These
      events are regulated by multiple cytokines and transcription factors which have
      both positive and negative effects. This article reviews the role of cytokines,
      as well as costimulatory and signaling pathways, involved in NK cell responses
      associated with resistance to infection.

PMID- 12505526
TI  - Human NK cells and their receptors.
AB  - The past decade has witnessed important progress in our understanding of how
      natural killer (NK) cells function. This is primarily consequent to the
      identification and functional characterization of MHC-specific inhibitory
      receptors that allow NK cells to discriminate between normal cells and
      potentially harmful cells that have lost or express insufficient amounts of MHC
      class I molecules. More recently, a number of activating receptors or coreceptors
      have been identified that are involved in the process of natural cytotoxicity but
      may also play a role in the direct recognition of pathogen-associated structures.
      Surprisingly, none of the triggering receptors identified in NK cells appears to
      be involved in the "NK-like activity" of a subset of CD8(+) cytolytic T
      lymphocytes. In this case, lysis of NK-susceptible tumor target cells is the
      result of the TCR alpha/beta-mediated recognition of HLA-E. The potent cytolytic
      activity of NK cells as well as their unique mode of functioning may be exploited
      in therapy. An important breakthrough is the recent report that "alloreactive" NK
      cells, generated in haploidentical bone marrow transplantation in patients with
      acute myeloid leukemias, may efficiently prevent leukemic relapses as well as
      graft rejection and graft-vs.-host disease. This may lead to a true revolution in
      bone marrow transplantation, based on the exploitation of appropriate HLA-Cl I
      mismatches that can put NK cells in action.

PMID- 12505527
TI  - Human natural killer cell deficiencies and susceptibility to infection.
AB  - There are a surprisingly large number of human natural killer (NK) cell
      deficiency states that provide insight into the role of NK cells in defense
      against human infectious disease. Many disorders associated with NK cell defects
      are caused by single gene mutations and, thus, give additional understanding
      concerning the function of specific molecules in NK cell development and
      activities. A resounding theme of NK cell deficiencies is susceptibility to
      herpesviruses, suggesting that unexplained severe herpesviral infection should
      raise the possibility of an NK cell deficit.

PMID- 12505528
TI  - 5-Hydroxytryptamine and platelets: uptake and aggregation in hypoxic pulmonary
      hypertensive rats.
AB  - Pulmonary hypertension is associated with various alterations in 5
      hydroxytryptamine (5-HT) physiology. In this study in platelets from hypoxic
      pulmonary hypertensive rats (10% O(2); 1 week) and normoxic rats (room air), (i)
      initial rates of specific [3H]5-HT uptake were measured and (ii) potentiation of
      collagen- and ADP-induced aggregation by 5-HT was quantified. The platelet count
      was almost halved in hypoxic rats. In uptake experiments, there was a decrease in
      5-HT uptake in platelets from hypoxic compared with normoxic rats, due to a 36%
      reduction in the maximal initial rate of uptake. The aggregation experiments
      showed that 5-HT (1-100 microM) increased the magnitude of responses to collagen
      and the duration of responses to ADP, but there was no difference between hypoxic
      and normoxic rats. Abnormalities in platelet function may conceivably lead to
      increases in plasma 5-HT levels in hypoxic pulmonary hypertension, but are
      unlikely to aggravate pulmonary thromboembolism.

PMID- 12505529
TI  - Agonist-specific down-regulation of the human delta-opioid receptor.
AB  - Down-regulation of the delta-opioid receptor contributes to the development of
      tolerance to delta-opioid receptor agonists. The involvement of the carboxy
      terminus of the mouse delta-opioid receptor in peptide agonist-mediated down
      regulation has been established. In the present study, we examined the down
      regulation of the truncated human delta-opioid receptor by structurally distinct
      delta-opioid receptor agonists. Chinese hamster ovary (CHO) cells, expressing the
      full-length or truncated epitope-tagged human delta-opioid receptors were
      incubated with various delta-opioid receptor agonists (100 nM, 24 h), and
      membrane receptor levels were determined by [(3)H]naltrindole saturation binding.
      Each delta-opioid receptor agonist tested down-regulated the full-length
      receptor. Truncation of the carboxy terminus abolished down-regulation by all
      delta-opioid receptor agonists, except SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4
      allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]N,N-diethylbenzamide). In
      addition, truncation of the C-terminus completely attenuated [D-Pen(2)-D
      Pen(5)]enkephalin (DPDPE), but not SNC80-mediated [32P] incorporation into the
      protein immunoreactive with an anti-epitope-tagged antibody. These findings
      suggest that SNC80-mediated phosphorylation and down-regulation of the human
      delta-opioid receptor involves other receptor domains in addition to the carboxy
      terminus. Pertussis toxin treatment did not block SNC80-mediated down-regulation
      of the truncated Et-hDOR, indicating that the down-regulation is independent of
      G(i/o) protein activation and subsequent downstream signaling.

PMID- 12505530
TI  - In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and
      buspirone on locus coeruleus neuronal activity.
AB  - The aim of the present study was to compare, in chloral-hydrate anaesthetized
      rats, the alpha(2)-adrenergic properties of the selective 5-HT(1A) receptor
      agonist, alnespirone (S-20499), with those of buspirone, a 5-HT(1A) receptor
      agonist exhibiting potent alpha(2)-adrenoceptor antagonist properties via its
      principal metabolite, 1-(2-pyrimidinyl)-piperazine. Both locus coeruleus
      spontaneous firing activity and noradrenaline release in the medial prefrontal
      cortex were potently inhibited by the alpha(2)-adrenoceptor agonist clonidine, at
      a dose of 40 microg/kg (i.p.). Such an inhibition was neither prevented nor
      reversed by alnespirone (10 mg/kg, i.p.), while buspirone, at the same dose,
      potently antagonized the locus coeruleus inhibitory effects of clonidine. These
      data demonstrate that, in contrast with some aryl-piperazine compounds (such as
      buspirone), alnespirone, either on its own or via a possible metabolite such as
      buspirone, is devoid in vivo of significant alpha(2)-adrenoceptor antagonist
      properties.

PMID- 12505531
TI  - Actions of cysteinyl leukotrienes in the enteric nervous system of guinea-pig
      stomach and small intestine.
AB  - Conventional intracellular microelectrodes, neuronal tracer injection techniques
      and immunohistochemistry were used to study the actions of cysteinyl leukotrienes
      (CysLTs) on electrical and synaptic behavior of enteric neurons in guinea-pig
      stomach and small intestine. Bath application of leukotriene C(4), leukotriene
      D(4) or leukotriene E(4) evoked a slowly activating depolarizing response in most
      of the myenteric and submucous plexus neurons in the small intestine while no
      effect was observed in gastric neurons. The depolarization evoked by cysteinyl
      leukotrienes in intestinal neurons was associated with increased input resistance
      and enhanced excitability. Suppression of hyperpolarizing after-potentials
      occurred in AH type neurons. The depolarizing action of cysteinyl leukotrienes
      was resistant to tetrodotoxin and cyclooxygenase inhibitors. Neither the CysLT(1)
      receptor antagonists (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3
      dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK 571), 1-[2
      hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl]-ethanone (LY 171883) and
      alpha-pentyl-3-(2-quinolinylmethoxy)-benzenemethanol (REV 5901), nor the dual
      CysLT(1)/CysLT(2) receptor antagonist 6(R)-(4'-carboxyphenylthio)-5(S)-hydroxy
      7(E),9(E),11(Z),14(Z)-eicosatetraenoic acid (BAY u9773) significantly altered the
      depolarizing action of the cysteinyl leukotrienes. Neurotransmission was
      unaffected by the cysteinyl leukotrienes. The results suggested involvement of
      cysteinyl leukotrienes in enteric immuno-neural communication through excitatory
      actions on enteric neurons. The receptor mediating these effects was distinct
      from currently recognized cysteinyl leukotriene receptor subtypes (CysLT(1) and
      CysLT(2) receptors) and may represent a new receptor subtype.

PMID- 12505532
TI  - Tolerance and dependence following chronic intracerebroventricular infusions of
      Tyr-D-Arg2-Phe-Sar4 (TAPS).
AB  - The dermorphin-derived tetrapeptide Tyr-D-Arg(2)-Phe-Sar(4) (TAPS) was tested for
      its ability to induce tolerance, cross-tolerance, withdrawal and its substitution
      properties in rats subjected to chronic intracerebroventricular (i.c.v.)
      infusions of mu-opiate receptor agonists. Tolerance and cross-tolerance were
      assessed by quantification of the thermally induced tail-flick response. Chronic
      intracerebroventricular infusion of TAPS resulted in antinociception at almost
      1000-fold lower doses compared to morphine sulphate and [D-Ala(2),
      MePhe(4)Gly(ol)(5)]enkephalin (DAMGO). Tolerance to the antinociceptive effect of
      TAPS developed similar to DAMGO and morphine sulphate. Cross-tolerance to
      intracerebroventricular bolus injections of DAMGO, but not of TAPS, was evident
      in rats rendered tolerant to morphine sulphate and TAPS. Naloxone-induced
      withdrawal was equally pronounced in animals treated with morphine sulphate,
      DAMGO or TAPS. TAPS substituted for morphine sulphate and vice versa regarding
      the withdrawal syndrome in a cross-over experimental design. In contrast to
      DAMGO, TAPS retains its antinociceptive effect following bolus administration in
      rats rendered tolerant to mu-opioid receptor agonists.

PMID- 12505533
TI  - Differential efficacy of intrathecal NMDA receptor antagonists on inflammatory
      mechanical and thermal hyperalgesia in rats.
AB  - Spinal cord dorsal horn N-methyl-D-aspartate (NMDA) receptors have been
      implicated in central sensitization, enhanced responsiveness to peripheral
      stimuli following peripheral injury. Since hyperalgesia is a behavioral
      consequence of central sensitization, it should be attenuated at the level of the
      dorsal horn with NMDA receptor antagonists. However, responsiveness to thermal
      and mechanical hyperalgesia may be distinct, and have thus far not been directly
      compared in chronic inflammatory pain models. In the present study, inflammation
      was induced with complete Freund's adjuvant (CFA) injected into the rat hind paw
      and NMDA receptor antagonists dizocilpine (MK-801) or 2-amino-5-phosphonovaleric
      acid (AP-5) were intrathecally injected in rats to determine the effects on both
      mechanical and thermal hyperalgesia. Locomotor tests and reflexes were also
      conducted to evaluate potential motor side effects. The NMDA receptor antagonists
      dose-dependently ameliorated mechanical hyperalgesia, but had marginal effects on
      thermal hyperalgesia. In ranges near antihyperalgesic doses, significant
      disruption of motor coordination was observed for both antagonists. These results
      suggest that, depending on the stimulus, NMDA receptors may have variable
      significance for central sensitization-mediated hyperalgesia, and that NMDA
      receptor antagonists may have therapeutic potential for some, but not all
      components in the clinical manifestation of inflammatory pain.

PMID- 12505534
TI  - Role of superoxide anion in pancreatic islet blood flow regulation in
      anesthetized rats.
AB  - The aim of the investigation was to study the influence of the superoxide anion
      on pancreatic islet blood flow in rats. For this purpose, blood flow measurements
      were conducted with a microsphere technique 10 min after intravenous
      administration of different doses of superoxide dismutase (5, 15, 50, 100 or 1000
      kU/kg body weight). In separate experiments, diethyldithiodicarbamate, an
      inhibitor of endogenous superoxide dismutase, was given to nontreated control
      rats or to rats subjected to a bilateral abdominal vagotomy before the injection.
      Only the highest dose of superoxide dismutase increased both whole pancreatic and
      islet blood flow. A 50% augmentation of fractional islet blood flow was seen.
      Administration of diethyldithiocarbamate induced marked hyperglycemia, which was
      partly prevented by vagotomy. Diethyldithiocarbamate decreased the whole
      pancreatic blood flow, while islet blood flow was maintained in both control and
      vagotomized rats. Consequently, a pronounced increase in fractional islet blood
      flow was noted in both these groups. We conclude that administration of
      superoxide dismutase and its inhibitor diethyldithiocarbamate influences
      pancreatic blood perfusion. In particular, superoxide dismutase causes a general
      increase in the whole pancreatic and islet blood flow, and an augmented
      fractional islet blood flow, presumably by a decrease in the local concentration
      of O(2)(z.rad;-), leading to increased concentration of NO.
      Diethyldithiocarbamate, on the other hand, by increasing the levels of
      O(2)(z.rad;-), decreases the whole pancreatic blood flow, whereas islet blood
      flow remains unaffected.

PMID- 12505535
TI  - Mechanisms underlying the hydrogen peroxide-induced, endothelium-independent
      relaxation of the norepinephrine-contraction in guinea-pig aorta.
AB  - The mechanisms underlying the hydrogen peroxide-induced relaxation of the
      norepinephrine-contraction were studied by measuring isometric force, myosin
      light chain (MLC(20)) phosphorylation and cyclic GMP in endothelium-denuded
      muscle from the guinea-pig aorta. Norepinephrine (5.2+/-1.3 microM) produced a
      phasic, followed by a tonic contraction. Hydrogen peroxide (10 and 100 microM),
      glyceryl trinitrate (30 and 300 nM) and 8-bromo cyclic GMP (30 and 100 microM)
      did not change the basal tone, but reduced the norepinephrine-induced
      contraction. Phosphorylation of MLC(20) (percentage of phosphorylated to total
      MLC(20)) was increased 1 min (5.9+/-1.0% vs. 35.9+/-4.9%) and, to a lesser
      extent, 20 min (3.7+/-1.7% vs. 13.9+/-1.6%) after the addition of norepinephrine.
      Hydrogen peroxide (100 microM) did not modify basal MLC(20) phosphorylation, but
      reduced the increase in MLC(20) phosphorylation induced by 1-min exposure to
      norepinephrine (20.9+/-4.1%). Its effect was abolished by catalase. When the
      tissue was incubated for 20 min with norepinephrine in the presence of hydrogen
      peroxide, norepinephrine-induced MLC(20) phosphorylation was not changed (13.6+/
      1.5%), as compared to that in the absence of hydrogen peroxide. Hydrogen peroxide
      relaxed norepinephrine-stimulated aortas in a concentration-dependent fashion
      with EC(50) values of 5.9+/-0.2 microM. The relaxation was inhibited by soluble
      guanylate cyclase inhibitors and increased by an inhibitor of cyclic GMP
      selective phosphodiesterase. In aorta precontracted with norepinephrine, hydrogen
      peroxide (100 microM) relaxed the tissue by 89+/-11% and almost doubled tissue
      concentrations of cyclic GMP, whereas sodium nitroprusside (1 microM) relaxed the
      tissue by 100% and increased cyclic GMP concentrations 30-fold. It is suggested
      that the inhibitory effects of hydrogen peroxide on the norepinephrine-induced
      phasic and sustained contractions are explained by a decrease in MLC(20)
      phosphorylation and by an alteration in MLC(20) phosphorylation-independent
      mechanisms, respectively. The effects of hydrogen peroxide were in part mediated
      by cyclic GMP.

PMID- 12505536
TI  - R+-methanandamide inhibits tracheal response to endogenously released
      acetylcholine via capsazepine-sensitive receptors.
AB  - The effects of cannabinoid drugs on the cholinergic response evoked by electrical
      field stimulation (0.2 ms pulse width, 20 V amplitude, 10 Hz, 7.5 s train
      duration) in guinea-pig tracheal preparations were investigated. The stable
      analogue of the endocannabinoid anandamide, R(+)-methanandamide (10(-7)-10(-4)
      M), produced a dose-dependent inhibition (up to 27+/-5% of control) of electrical
      field stimulation-mediated atropine-sensitive response. This effect was not
      blocked by the selective cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)
      5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide
      hydrochloride (SR 141716A; 10(-6) M), and was not reproduced with the cannabinoid
      CB(1)/CB(2) receptor agonist R(+)-[2,3-dihydro-5-methyl
      [(morpholinyl)methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl]-(1
      naphthalenyl)methanone mesylate) (WIN 55,212-2; 10(-8)-10(-5) M) or the
      cannabinoid CB(2) receptor selective agonist 1-propyl-2-methyl-3-(1
      naphthoyl)indole (JWH-015; 10(-8)-10(-5) M); it was, on the contrary, antagonized
      by the vanilloid antagonist 2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8
      dihydroxy-2,3,4,5-tetrahydro-1H-2 benzazepine (capsazepine; 10(-6) M). At the
      postjunctional level, neither R(+)-methanandamide nor WIN 55,212-2 nor JWH-015
      did affect tracheal contractions induced by exogenous acetylcholine (10(-6) M).
      An inhibitory vanilloid receptor-mediated effect on the cholinergic response
      evoked by electrical stimulation was confirmed with the vanilloid agonist
      capsaicin, at doses (3-6 x 10(-8) M) which poorly influenced the basal smooth
      muscle tone of trachea. In conclusion, our data indicate that in guinea-pig
      trachea (a) neither CB(1) nor CB(2) cannabinoid receptor-mediated modulation of
      acetylcholine release occurs; (b) vanilloid VR1-like receptors appear involved in
      R(+)-methanandamide inhibitory activity on the cholinergic response to electrical
      field stimulation.

PMID- 12505537
TI  - Antiemetic and motor-depressive actions of CP55,940: cannabinoid CB1 receptor
      characterization, distribution, and G-protein activation.
AB  - Dibenzopyran (Delta(9)-tetrahydrocannabinol) and aminoalkylindole [R(+)-[2,3
      dihydro-5-methyl-3-[(morpholinyl)methyl]pyrolol[1,2,3-de]-1,4-benzoxazin-yl]-(1
      naphthalenyl) methanone mesylate; (WIN55,212-2)] cannabinoids suppress vomiting
      produced by cisplatin via cannabinoid CB(1) receptors. This study investigates
      the antiemetic potential of the "nonclassical" cannabinoid CP55,940 [1alpha,2beta
      (R)-5alpha]-(-)-5-(1,1-dimethyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl
      phenol] against cisplatin-induced vomiting and assesses the presence and
      functionality of cannabinoid CB(1) receptors in the least shrew (Cryptotis parva)
      brain. CP55,940 (0.025-0.3 mg/kg) reduced both the frequency of cisplatin-induced
      emesis (ID(50)=0.025 mg/kg) and the percentage of shrews vomiting (ID(50)=0.09
      mg/kg). CP55,940 also suppressed shrew motor behaviors (ID(50)=0.06- 0.21 mg/kg)
      at such doses. The antiemetic and motor-suppressant actions of CP55,940 were
      countered by SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4
      methylpyrazole-3-carboxamide], indicating both effects are cannabinoid CB(1)
      receptor-mediated. Autoradiographic studies with [3H]-SR141716A and [35S]
      GTPgammaS binding revealed that the distribution of the cannabinoid CB(1)
      receptor and its activation pattern are similar to rodent brain and significant
      levels are present in brain loci (e.g., nucleus tractus solitarius (NTS)) that
      control emesis. The affinity rank order of structurally diverse cannabinoid
      ligands for cannabinoid CB(1) receptor in shrew brain is similar to rodent brain:
      HU-210=CP55,940=SR141716A>/=WIN55,212-2>/=delta-9
      tetrahydrocannabinol>methanandamide=HU-211=cannabidiol=2-arachidonoylglycerol.
      This affinity order is also similar and is highly correlated to the cannabinoid
      EC(50) potency rank order for GTPgammaS stimulation except WIN55,212-2 and delta
      9-tetrahydrocannabinol potency order were reversed. The affinity and the potency
      rank order of tested cannabinoids were significantly correlated with their
      antiemetic ID(50) potency order against cisplatin-induced vomiting
      (CP55,940>WIN55,212-2=delta-9-tetrahydrocannabinol) as well as emesis produced by
      2-arachidonoylglycerol or SR141716A (CP55,940>WIN55,212-2>delta-9
      tetrahydrocannabinol).

PMID- 12505538
TI  - Differential distribution of functional cannabinoid CB1 receptors in the mouse
      gastroenteric tract.
AB  - Recently, the gastrointestinal pharmacology of cannabinoid CB(1) receptors has
      been extensively explored. We employed western blotting and immunohistochemistry
      techniques to study the distribution of the cannabinoid CB(1) receptor protein in
      the mouse gastroenteric tract. The cannabinoid CB(1) receptor peptide was
      detected by western blotting only in its glycosylated form (63 kDa) with a
      significant differential distribution. The highest levels of expression were
      detected in the stomach and in the colon, while the pyloric valve was devoid of
      any cannabinoid CB(1) receptor protein. The immunohistochemical study showed
      intense cannabinoid CB(1) receptor immunoreactivity in ganglia subadjacent to the
      gastric epithelium and in the smooth muscle layers of both the small and large
      intestine. Only the small intestine showed (-)-3-[2-hydroxyl-4-(1,1
      dimethylheptyl)-phenyl]-4-(3-hydroxylpropyl) cyclohexan-1-ol) ([3H]CP 55,940)
      specific binding (27%). These receptors mediated pharmacologically significant
      effects since the cannabinoid CB(1) receptor agonist R(-)-7-hydroxy-delta-6-tetra
      hydrocannabinol-dimethylheptyl (HU 210) dose dependently inhibited
      gastrointestinal transit up to 70%, while the cannabinoid CB(1) receptor
      antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4
      methylpyrazole-3-carboxamide (SR 141716A) increased gastrointestinal transit.
      Moreover, the dose of 0.3 microg/kg of HU 210, devoid per se of any activity on
      mouse intestinal propulsion, blocked the increased gastroenteric transit induced
      by the cannabinoid CB(1) antagonist SR 141716A.

PMID- 12505539
TI  - Inhibition of macrophage activation and lipopolysaccaride-induced death by seco
      steroids purified from Physalis angulata L.
AB  - Physalis angulata L. is an annual herb widely used in popular medicine for the
      treatment of a variety of pathologies. Here, we tested immunomodulatory
      activities of physalins, seco-steroids purified from P. angulata extracts.
      Addition of physalins B, F or G, but not D, caused a reduction in nitric oxide
      production by macrophages stimulated with lipopolysaccaride and interferon-gamma.
      In the presence of physalin B, macrophages stimulated with lipopolysaccaride,
      alone or in combination with interferon-gamma, produced lower levels of tumour
      necrosis factor (TNF)-alpha, interleukin-6 and interleukin-12. The inhibitory
      activity of physalin B, unlike that of dexamethasone, was not reversed by RU486
      [(4-dimethylamino) phenyl-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one], an
      antiglucocorticoid. Physalin B-treated mice had lower levels of serum TNF-alpha
      than control mice after lipopolysaccaride challenge. More importantly, mice
      injected with physalins B, F or G survived after a lethal lipopolysaccaride
      challenge. These results demonstrate that seco-steroids from P. angulata are
      potent immunomodulatory substances and act through a mechanism distinct from that
      of dexamethasone.

PMID- 12505540
TI  - Alpha-adrenergic blockade: a possible mechanism of tocolytic action of certain
      benzodiazepines in a postpartum rat model in vivo.
AB  - Benzodiazepines are frequently used for the treatment of maternal psychiatric
      disorders during pregnancy. Besides their anxiolytic effect, they are reported to
      exert a direct relaxing action on several smooth muscle preparations, including
      the uterus. In the present study, the possibility of the involvement of alpha(1)
      adrenergic receptors in this peripheral effect is investigated. The tocolytic
      potencies of diazepam, midazolam and nitrazepam are assessed in vivo in a
      postpartum rat model, together with other drugs known to bind to alpha
      adrenoceptors (e.g. alpha(1)-antagonists, tricyclic compounds and droperidol).
      The interactions of some benzodiazepines and norepinephrine were also examined in
      an isolated in vitro system. The affinities of these agents for the receptor in
      question were additionally tested by radioligand displacement assay. A
      correlation was found between the tocolytic potencies and inhibition constants of
      the tested drugs, suggesting that the smooth muscle-relaxing effect of these
      benzodiazepines is mediated through modulation of the alpha(1)-adrenergic
      receptors.

PMID- 12505541
TI  - Kynurenines and the respiratory parameters on rat heart mitochondria.
AB  - It has been shown recently that the L-kynurenine metabolite kynurenic acid lowers
      the efficacy of mitochondria ATP synthesis by significantly increasing state IV,
      and reducing respiratory control index and ADP/oxygen ratio of glutamate/malate
      consuming heart mitochondria. In the present study we investigated the effect of
      L-tryptophan (1.25 microM to 5 mM) and other metabolites of L-kynurenine as 3
      hydroxykynurenine (1.25 microM to 2.5 mM), anthranilic acid (1.25 microM to 5 mM)
      and 3-hydroxyanthranilic acid (1.25 microM to 5 mM) on the heart mitochondria
      function. Mitochondria were incubated with saturating concentrations of
      respiratory substrates glutamate/malate (5 mM), succinate (10 mM) or NADH (1 mM)
      in the presence or absence of L-tryptophan metabolites. Among tested substances,
      3-hydroxykynurenine, 3-hydroxyanthranilic acid and anthranilic acid but not
      tryptophan affected the respiratory parameters dose-dependently, however at a
      high concentration, of a micro molar range. 3-Hydroxykynurenine and 3
      hydroxyanthranilic acid lowered respiratory control index and ADP/oxygen ratio in
      the presence of glutamate/malate and succinate but not with NADH. While,
      anthranilic acid reduced state III oxygen consumption rate and lowered the
      respiratory control index only of glutamate/malate-consuming heart mitochondria.
      Co-application of anthranilic acid and kynurenic acid (125 or 625 microM each) to
      glutamate/malate-consuming heart mitochondria caused a non-additive deterioration
      of the respiratory parameters determined predominantly by kynurenic acid.
      Accumulated data indicate that within L-tryptophan metabolites kynurenic acid is
      the most effective, followed by anthranilic acid, 3-hydroxykynurenine, 3
      hydroxyanthranilic acid to influence the respiratory parameters of heart
      mitochondria. Present data allow to speculate that changes of kynurenic acid
      and/or anthranilic acid formation in heart tissue mitochondria due to fluctuation
      of L-kynurenine metabolism may be of functional importance for cardiovascular
      processes. On the other hand, beside the effect of 3-hydroxyanthranilic acid and
      3-hydroxykynurenine on respiratory parameters, their oxidative reactivity may
      contribute to impairment of mitochondria function, too.

PMID- 12505542
TI  - Apomorphine-susceptible and apomorphine-unsusceptible Wistar rats differ in their
      recovery from stress-induced ulcers.
AB  - The aim of the present study was to investigate the effects of restraint-in-water
      stress on gastric ulcerations in two fundamentally different types of animals:
      the apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS)
      rats. APO-SUS and APO-UNSUS do not only differ in their susceptibility to the
      dopamine agonist apomorphine, but also in stress-induced release of mesolimbic
      dopamine and corticosterone. All three factors are known to either predict or be
      involved in gastric ulceration. The results showed that immediately after the
      stressor the ulcerations in APO-SUS and APO-UNSUS rats were not line-specific. On
      the contrary, the recovery from gastric ulceration varied between both types of
      rat: APO-SUS rats did not show any sign of recovery after 6 hours whereas APO
      UNSUS rats significantly recovered during the period of 0-6 hr after the
      stressor. It is hypothesised that this difference is due to the fact that APO
      UNSUS rats are characterised by a less and shorter-lasting stress-induced
      increase of corticosterone. This study provides evidence that the pathological
      effects of exposure to stressors significantly differ between APO-SUS and APO
      UNSUS rats and that genetic factors may direct the process of recovering from
      ulcers.

PMID- 12505543
TI  - Relationship between blood pressure and Alzheimer's disease in Linxian County,
      China.
AB  - To investigate the relationship between hypertension and Alzheimer's disease(AD)
      and the change of Alzheimer's patients' blood pressure(BP) before and after the
      onset of AD, we conducted this epidemiological study. Subjects for this study
      were individuals who participated in a large scale, randomized controlled trial
      of nutritional intervention from 1984 to 1991. Participants were initially
      screened for dementia using Chinese Mini-Mental State Examination (CMMS) and
      Activities of Daily Living (ADL). Positive subjects were subsequently
      administered a detailed neuropsychological and neurobehavioral examination. The
      diagnosis of AD was made by a consensus conference of psychiatrists using
      Diagnostic And Statistical Manual Of Mental Disorders-Fourth Edition(DSM-IV)
      criteria. 16488 subjects were examined and 301 were diagnosed as AD. We compared
      the prevalence of AD in different populations that were stratified with 1984's
      systolic or diastolic blood pressure(those four stratifications being high blood
      pressure, borderline blood pressure, normal, low blood pressure), and compared
      the change of blood pressure of 301 AD patients between 1984 and 1999-2000, which
      is before and after the onset of AD respectively. Multiple Logistic Regression
      (1:1 nested case-control study) was used to assess if hypertension is an
      independent risk factor for AD, and Trend test was used to assess the
      relationship between blood pressure and AD. Here we demonstrate that there was a
      significant difference in AD prevalence among different populations stratified by
      systolic or diastolic blood pressure (P < 0.01). The prevalence is highest in
      hypertension group, and lowest in hypotension group. Multiple Logistic Regression
      identified high blood pressure as a risk factor for AD (OR = 1.97, 95%CI:1.09
      3.54, P = 0.02). Trend test showed that there is a significant dose-response
      relationship between blood pressure and AD (P < 0.0002). For hypertensive AD
      patients, there was no significant difference in systolic blood pressure(SBP)
      before and after the onset of AD, but diastolic blood pressure(DBP) decreased
      dramatically after the onset of AD (P < 0.01); however, the result also showed
      that DBP decrease occurred in the non-demented group. Based on this, we think the
      DBP decrease is not related to AD. We further investigated whether BP values
      differed crossed-sectionally between the AD-patients and non-demented
      individuals. We found that regardless of SBP or DBP, the BP values of the AD
      group were all significantly higher than that of non-demented. In summary, these
      data suggest there is a strong relationship between hypertension and AD; however,
      the mechanism remains to be studied.

PMID- 12505544
TI  - Role of tachykinins in the bronchoconstriction induced by HCl intraesophageal
      instillation in the rabbit.
AB  - Gastroesophageal acid reflux (GER) is a common disorder associated with the
      exacerbation of asthma. In this study we investigated the effects on the airways
      of intraoesophageal HCl instillation in the rabbit and the role of tachykinins in
      these effects. In anaesthetized New Zealand rabbits bronchopulmonary functions
      [total lung resistance (R(L)) and dynamic compliance (C(dyn))] were calculated
      before and after HCl intraoesophageal instillation. Infusion of HCl induced a
      significant bronchoconstriction (P < 0.05) in the terms of R(L) and C(dyn)
      changes, that were increased by phosphoramidon pre-treatment and reduced by
      capsaicin pre-treatment. Moreover, a pre-treatment with SR 48968, a tachykinin
      NK2 receptor antagonist, or SR 140333, a NK1 receptor antagonist, significantly
      inhibited the bronchoconstriction induced by intraoesophageal HCl infusion in
      terms of R(L) and C(dyn)changes. Finally, the HCl induced bronchoconstriction was
      unaffected by SR 142801, a tachykinin NK3 receptor antagonist. In conclusion
      these results suggest that bronchoconstriction induced by intraoesophageal HCl
      infusion is mainly dependent on the release of tachykinins and that both NK1 and
      NK2 tachykinin receptors are involved.

PMID- 12505545
TI  - Biological response of human aortic endothelial cells exposed to acellular
      hemoglobin solutions developed as potential blood substitutes.
AB  - The cardiovascular effects of hemoglobin-based oxygen carriers (HBOCs) are mainly
      related to their nitric oxide (NO) scavenging properties but other effects such
      as the impact of these hemoglobins on the endothelial cell (EC) biology are not
      well understood. We hypothesized that HBOCs could modify EC functions by altering
      gene expression, in particular the endothelial NO synthase (NOS3) and/or by
      activating EC. Cultured human aortic endothelial cells (HAEC) were incubated for
      3 hours with purified cell-free Hb, Dex-BTC-Hb or alpha alpha-Hb (16 g/L).
      Expression of NOS3 mRNA and protein were assessed by semi-quantitative RT-PCR and
      Western blot respectively immediately after and 24 hours after incubation. The
      expression and localization of the adhesion molecule ICAM-1 were detected by
      fluorescence microscopy. None of the solutions tested modified NOS3 mRNA and
      protein expression despite adequate controls that up- or down-regulate NOS3
      expression. The expression and the localization of ICAM-1 on the cell membrane
      were modified after 3 hours of incubation with all the hemoglobin solutions
      tested in a manner similar to tumor necrosis factor-alpha. In conclusion, HAEC
      incubation with clinically relevant concentrations of HBOCs induced changes in
      the pattern of ICAM-1 expression consistent with cell activation/cell signaling
      mechanisms. However, HBOCs did not alter NOS3 gene expression.

PMID- 12505546
TI  - Exposure to the environmental estrogen bisphenol A differentially modulated
      estrogen receptor-alpha and -beta immunoreactivity and mRNA in male mouse testis.
AB  - We examined the effects of bisphenol A (0.5 microg/ml or 50 microg/ml) in the
      drinking water on estrogen receptor (ER) alpha and beta proteins and mRNA in the
      testis of young mice following 8-weeks of oral administration of bisphenol A
      utilizing immunohistochemistry and semiquantitative reverse transcription
      polymerase chain reaction amplification (RT-PCR). ER beta was clearly localized
      in the nuclei of spermatogonia and/or spermatocytes. ER beta immunopositive cell
      numbers per testis section were significantly decreased in the 50 microg/ml
      bisphenol A-treated group compared with control and the 0.5 microg/ml bisphenol A
      treated group. The number of ER alpha positive cells in the testis was
      significantly lower than ER beta positive cells in control group. ER alpha
      immunopositive cell numbers per testis section were markedly increased in the 50
      microg/ml bisphenol A-treated group compared with the control and the 0.5
      microg/ml bisphenol A-treated group. ER beta mRNA expression was significantly
      decreased in the 50 microg/ml bisphenol A-treated group compared with the control
      and the 0.5 microg/ml bisphenol A-treated group. In contrast, ER alpha mRNA
      expression was markedly increased in the 50 microg/ml bisphenol A-treated group
      compared with the control and the 0.5 microg/ml bisphenol A-treated group. The
      existence of ER alpha and beta in the testis suggests that estrogens directly
      affect germ cells during testicular development and spermatogenesis, and
      differential modulation of ER alpha and beta in the testis could be involved in
      the effects of bisphenol A.

PMID- 12505547
TI  - Effects of cysteine on amino acid concentrations and transsulfuration enzyme
      activities in rat liver with protein-calorie malnutrition.
AB  - The changes in amino acid concentrations and transsulfuration enzyme activities
      in liver were investigated after 4-week fed on 23% casein diet (control group)
      and 5% casein diet without (protein-calorie malnutrition, PCM group) or with
      (PCMC group) oral administration of cysteine, 250 mg/kg (twice daily, starting
      from the fourth week) using rats as an animal model. By supplementation with
      cysteine in PCM rats (PCMC group), cysteine level was elevated almost close to
      the control level, and glutathione (GSH), aspartic acid and serine levels were
      restored greater than the control levels. The measurement of transsulfuration
      enzyme activities exhibited that gamma-glutamylcysteine ligase (gamma-GCL)
      activity was up-regulated in rats with protein restriction (PCM group), and
      cysteine supplementation (PCMC group) down-regulated to the control level. One
      week supplementation of cysteine (PCMC group) significantly down-regulated the
      cysteine sulfinate decarboxylase activity. These results indicate that the
      availability of sulfur amino acid(s) especially cysteine appears to play a role
      in determining the flux of cysteine between cysteine catabolism and GSH
      synthesis.

PMID- 12505548
TI  - Cell kinetics-dependent antitumor effect of irinotecan hydrochloride induced by
      the synchronizing effect of hydroxyurea: cell kinetics and dosing time.
AB  - Influence of hydroxyurea (HU) on the antitumor effect of irinotecan hydrochloride
      (CPT-11) was investigated in ICR male mice transplanted with sarcoma 180 cells (S
      180). A single dose of CPT-11 (100 mg/kg) was injected at various times after a
      single dose of HU (300 mg/kg). The relative tumor weight varied significantly
      depending on the timing of CPT-11 injection after HU injection (P < 0.01). The
      higher antitumor effect of CPT-11 was observed when DNA synthesis of S-180 cells
      increased (20 hr), and the lower effect was observed when the DNA synthesis
      decreased (0 hr). The loss of body weight also varied significantly depending on
      the timing of CPT-11 injection after HU injection (P < 0.01). The toxicity of CPT
      11 was higher when the inhibitory effect of HU on DNA synthesis of bone marrow
      cells was stronger (15 hr), and the lower toxicity was observed when the
      inhibitory effect was not observed (0 hr). The plasma SN-38 concentration at 2 hr
      after CPT-11 injection was higher at 20 hr after HU injection than at 0 hr after
      HU injection. The difference in plasma esterase activity between 0 hr and 20 hr
      after HU injection was regarded as the mechanism underlying the dosing time
      dependent difference of the SN-38 concentration. These experiments suggest that
      HU can produce a different phase of cell cycle between tumor cells and normal
      cells. This leads to increase the antitumor effect of CPT-11 without increasing
      the adverse effect of the drug. It is essential to consider the dosing time in
      the two-drug combination therapy.

PMID- 12505549
TI  - Regulation of prostaglandin generation in carrageenan-induced pleurisy by
      inducible nitric oxide synthase in knockout mice.
AB  - In the present study, by comparing the responses in wild-type mice (iNOSWT) and
      mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we
      investigated the correlation between endogenous nitric oxide (NO) and
      prostaglandin (PG) generation in carrageenan-induced pleurisy. The inflammatory
      response in iNOSKO mice was significantly reduced in respect to iNOSWT animals,
      as demonstrated by the exudate volume (-63%) and numbers of infiltrating cells (
      62%). The levels of NOx in the pleural exudate from carrageenan-treated mice were
      significantly (p < 0.01) decreased in iNOSKO mice (16 +/- 7.6 nmoles/mice)
      compared to iNOSWT animals (133 +/- 9 nmoles/mice). Similarly, the amounts of
      PGE2 in the pleural exudates of carrageenan-treated animals were significantly (p
      < 0.01) lower in iNOSKO compared to iNOSWT mice (120 +/- 20 pg/mice vs. 308 +/-
      51 pg/mice). Also the amounts of 6-keto-PGF(1 alpha) produced by lungs from
      carrageenan-treated iNOSKO mice (1.01 +/- 0.10 ng/tissue mg) were significantly
      (p < 0.01) reduced compared to iNOSWT carrageenan-treated mice (2.1 +/- 0.09
      ng/tissue mg). In conclusion our results confirm, by the use of iNOSKO mice that
      in carrageenan-induced pleurisy NO positively modulates PG biosynthesis.

PMID- 12505550
TI  - P300 amplitude in subjects with primary insomnia is modulated by their sleep
      quality.
AB  - OBJECTIVE: The hyperarousal hypothesis is evaluated while controlling the
      influence of the quality of sleep in the night preceding the evaluation. METHOD:
      Eleven primary insomniacs and 11 healthy age matched controls participated to the
      study. Participants filled in 2 weeks of sleep logs and self-monitored their
      subjective tension the evening before and the morning after each night.
      Afterwards, subjects were called in to the Lab for a recording session of the
      P300 ERP (oddball paradigm) once after a night of bad sleep quality (N-) and once
      after a night of good sleep quality (N+). RESULTS: The main result of the present
      study indicated that the P300 amplitude at Fz in insomniacs resulted higher
      following a N- and lower following a N+ with respect to controls. CONCLUSIONS:
      This result suggests that cortical hyperarousal in primary insomniacs is not a
      stable individual characteristic, but is associated with the poor quality of
      their nocturnal sleep.

PMID- 12505551
TI  - 'Young old' and 'old old' poor sleepers with and without insomnia complaints.
AB  - OBJECTIVE: Sleep, psychological adjustment, health and insomnia complaints were
      examined in 277 community-dwelling seniors in order to identify characteristics
      that distinguish poor sleepers with complaints (likely to seek treatment) and
      those without complaints (unlikely to seek treatment). METHODS: Two weeks of
      sleep diaries and other sleep-related measures were collected. Young old (65-74
      years) and old old (75+) participants were categorized as: good sleepers, poor
      sleepers with complaints (complainers), and poor sleepers without complaints
      (noncomplainers). RESULTS: In both age groups, complainers had poorer sleep than
      noncomplainers. Complainers also reported more depressive symptoms and had poorer
      health than noncomplainers. The old old slept longer each night, but took longer
      to fall asleep, napped more, and were more likely to complain of insomnia than
      the young old; otherwise, the young old/old old distinction did not explain sleep
      differences among the three types of sleepers. CONCLUSIONS: Implications for
      treating late-life insomnia include greater inclusion of the old old in treatment
      outcome research and more focus on the development of integrated intervention and
      prevention strategies that target health, depressive symptoms, and sleep.

PMID- 12505552
TI  - Predicting longer-term outcomes following psychological treatment for hypnotic
      dependent chronic insomnia.
AB  - OBJECTIVES: To identify predictors of treatment adherence, patient dropout, and
      treatment response among long-term hypnotic users recruited into a randomized
      controlled trial of psychological treatment for insomnia. METHODS: Of 108
      treatment and 101 control patients initially recruited, 37 treatment group
      patients (34.3%) failed to complete all 6 sessions (i.e., were nonadherent),
      while across both groups 61 (29.2%) patients failed to return postal assessments
      at 3-month follow-up (i.e., dropped out). Relationships between baseline
      characteristics and adherence (adherent vs. nonadherent) and attrition (dropout
      vs. nondropout) were examined in discriminant models. Relationships between
      baseline characteristics and treatment response (sleep quality, sleep latency,
      sleep efficiency, and hypnotic drug use) were examined in a series of multiple
      regression models. RESULTS: Adherent patients showed a significantly greater
      severity of pretreatment sleep disturbance, as measured by the Pittsburgh Sleep
      Quality Index (PSQI). Dropout at 3 months was associated with significantly lower
      perceived health status at baseline. In the regression models, lower Cure/Control
      subscale scores from the Illness Perception Questionnaire (IPQ) predicted greater
      posttreatment improvements in sleep efficiency and PSQI scores, while lower
      baseline anxiety scores predicted a posttreatment increase in hypnotic-free
      nights/week. CONCLUSION: In routine clinical practice settings, higher anxiety
      and a less positive attitude towards symptom control were associated with poorer
      treatment response. Adherence and attrition show a different pattern of
      associations, with greater need (as indexed by insomnia severity) predicting
      higher levels of service uptake and poorer general health predicting a higher
      likelihood of dropout.

PMID- 12505553
TI  - Trait anxiety and sleep-onset insomnia: evaluation of treatment using anxiety
      management training.
AB  - OBJECTIVES: This study was initially designed to test the notion that generalized
      anxiety is a predominant factor in the maintenance of psychologically determined
      sleep-onset insomnia and that a trait anxiety reducing technique can provide
      significant therapeutic gains. METHODS: Twenty participants (age 19-63) with
      moderate to severe sleep-onset chronic insomnia were first asked to monitor their
      sleep-onset latency (SOL) for a 3-week baseline period at home using a SOL clock
      device. Then, 10 received anxiety management training (AMT) for 9 weeks, while
      the remaining 10 were trained in the use of progressive relaxation (PR). All
      participants were measured before and after therapy using sleep laboratory
      recordings (three nights each), the Spielberger Trait Anxiety Inventory and the
      Beck Depression Inventory. Daily home sleep-onset measures with the SOL clock
      device were also taken during therapy. RESULTS: There was no change in SOL over
      the 3-week baseline period. However, both groups experienced a significant
      improvement in SOL from pretreatment (end of baseline) to posttreatment periods.
      In the laboratory, both groups experienced a reduction in Stage 1 sleep as well
      as an increase in slow wave sleep (SWS) and sleep satisfaction. On the
      personality measures, both groups experienced a significant reduction in trait
      anxiety and a decrease in depression. Overall, there was no indication that one
      of the therapies was significantly better than the other in effecting changes.
      CONCLUSION: These results suggest that both PR and AMT are efficient therapies
      for sleep onset insomnia and overall sleep quality. Improvements in the
      application of the AMT technique are proposed to maximize its usefulness.

PMID- 12505554
TI  - Cognitive performance and sleep quality in the elderly suffering from chronic
      insomnia. Relationship between objective and subjective measures.
AB  - OBJECTIVE: The objective of the present study was to evaluate the relationship
      between objective and subjective sleep quality and objective and subjective
      evaluation of cognitive performance in older adults suffering of chronic insomnia
      (using or not benzodiazepines, BZs) or self-reported good sleepers. METHODS:
      Three groups of participants 55 years and older were evaluated: 20 insomnia
      sufferers using BZs chronically, 20 drug-free insomnia sufferers and 20 good
      sleepers. Objective sleep (PSG) and subjective sleep (sleep diaries, SD) were
      measured. Objective measures of cognitive performance (attention/concentration,
      verbal/visual memory, executive function and psychomotor speed) and subjective
      perception of daily performance were evaluated. RESULTS: Correlational analysis
      revealed that objective and subjective measures of daytime performance are
      differentially related to sleep quality for the three groups. An objective good
      night of sleep is associated with better cognitive performance in good sleepers
      and drug-free individuals. On the other hand, the impression of having slept well
      is related to better cognitive performance in good sleepers and chronic insomnia
      sufferers using BZs. CONCLUSION: Daytime performance and sleep quality are
      related, but differently so for a good sleeper, an insomnia sufferer without
      treatment, or one using BZs to alleviate sleep difficulties.

PMID- 12505555
TI  - On the comparability of pharmacotherapy and behavior therapy for chronic
      insomnia. Commentary and implications.
AB  - OBJECTIVES: Recently, we undertook an empirical review using meta-analytic
      techniques to assess the extent to which these therapeutic strategies produce
      comparable outcomes. No differences between the two therapeutic strategies were
      found, except for sleep latency (SL). Behavior therapy demonstrated a greater
      reduction in latency to sleep onset as compared to pharmacotherapy. In the
      present paper, we provide a brief summary of our meta-analysis and then (1)
      critically review the outcomes and (2) place the findings into a larger context
      that takes into account what factors represent barriers to treatment and how can
      we insure that in the future patients will have increased access to behavioral
      sleep medicine services.

PMID- 12505556
TI  - Distinguishing between excessive daytime sleepiness and fatigue: toward improved
      detection and treatment.
AB  - INTRODUCTION: Excessive daytime sleepiness (EDS) and fatigue occur in high
      percentages in the general population. They are common complaints in primary care
      and in specialty medicine. Although they may represent distinct or overlapping
      phenomena, the general medical literature does not normally distinguish between
      EDS and fatigue. Despite their prevalence, both EDS and fatigue are identified
      and treated in a relatively small proportion of those affected. The similarity of
      EDS and fatigue may create diagnostic ambiguity and thereby contribute to under
      identification and under-treatment. Fatigue, in particular, is thought to be
      difficult to manage when it is identified. METHODS: The literature was searched
      for reviews, meta-analysis and similar levels of papers focused on EDS or
      fatigue. RESULTS: EDS and fatigue are operationalized in ways that contribute to
      blurring rather than to distinguishing between them. Existing measures of both
      EDS and fatigue may also contribute to their misidentification. Effective
      treatments for both symptoms have been established. Behavioral interventions are
      effective and underutilized. DISCUSSION: We suggest more precise
      operationalization of EDS and fatigue, leading to a refinement of existing
      measures or development of new tools, a structured interview with fatigue and EDS
      sections in the clinical setting, and more consideration for behavioral
      interventions.

PMID- 12505557
TI  - Neuropsychological changes and treatment compliance in older adults with sleep
      apnea.
AB  - INTRODUCTION: Apnea is a common disorder in older adults and has been shown to
      affect cognition. Some studies suggest that treatment for apnea improves certain
      cognitive deficits, but few studies have examined the relationship between
      compliance and cognitive improvement. We designed a study to answer the following
      questions about sleep apnea, cognition and treatment in older adults: (1) Which
      neuropsychological (NP) variables are differentially associated with measures of
      sleep fragmentation and oxygen desaturation? (2) Does compliant use of CPAP
      provide a cognitive advantage over noncompliant use? (3) Does NP performance at
      baseline predict compliance at 3 months? METHOD: Twelve participants were
      recruited for the study. All had polysomnographically defined sleep apnea with an
      RDI of 10 or greater. All were also at least 55 years of age, had no other
      diagnosable sleep disorder and had no previous treatment for sleep apnea syndrome
      (SAS). Participants were administered a full NP battery before and 3 months after
      treatment with CPAP. RDI at baseline was associated with delayed verbal recall,
      while oxygen desaturation was associated with both delayed recall and
      constructional abilities. Compliant use of CPAP at 3 months was associated with
      greater improvements in attention, psychomotor speed, executive functioning and
      nonverbal delayed recall. Finally, attention measures predicted compliance at 3
      months suggesting that those who were least vigilant at baseline were more likely
      to comply with treatment. DISCUSSION: Results are discussed in terms of the
      relevance to targeting special populations for compliance interventions, the ways
      that treatment may specifically affect older adults and the possible dose
      response relationship of CPAP.

PMID- 12505558
TI  - Sleep and chronic pain: challenges to the alpha-EEG sleep pattern as a pain
      specific sleep anomaly.
AB  - OBJECTIVE: The alpha-EEG sleep anomaly has been associated with chronic benign
      pain syndromes. Although controversial, the anomaly is believed by some to be an
      important biologic correlate of certain otherwise poorly explained painful
      conditions (e.g., fibromyalgia and chronic fatigue syndrome). To shed further
      light on this phenomenon, this study compared the sleep and psychological
      characteristics of chronic pain patients who exhibited the alpha-EEG sleep
      anomaly with pain-free psychiatric and medical patients who also were found to
      exhibit the alpha-EEG anomaly. METHODS: The alpha-EEG sleep was identified in the
      polysomnographic records of 5% of over 1000 consecutive sleep patients. Objective
      sleep parameters, daytime sleepiness and psychological characteristics (Minnesota
      Multiphasic Personality Inventory [MMPI] scores) of patients exhibiting this
      anomaly were examined. RESULTS: The alpha-EEG anomaly was identified in only 5%
      of the total patient sample. Patients with the alpha-EEG anomaly could be further
      classified into three diagnostic subgroups: chronic pain, psychiatric and other
      medical/sleep disorders, The subgroups were compared on sleep parameters and
      psychological characteristics. Less than 40% of the patients exhibiting the alpha
      EEG anomaly experienced chronic pain. Chronic pain patients evidenced disturbed
      sleep patterns and psychological characteristics that were for the most part
      similar to those observed in some pain-free medical and psychiatric patients.
      Only the medical subgroup exhibited objective daytime sleepiness. The alpha-EEG
      sleep disturbance was not accounted for by psychological characteristics.
      CONCLUSIONS: These findings challenge the notion that alpha-EEG sleep is of
      direct etiological significance in producing the pain complaint among patients
      with chronic pain since the alpha-EEG sleep was not a sufficient condition for
      pain.

PMID- 12505559
TI  - The efficacy of mindfulness-based stress reduction in the treatment of sleep
      disturbance in women with breast cancer: an exploratory study.
AB  - OBJECTIVE: The diagnosis of breast cancer, the most common type of cancer among
      American women, elicits greater distress than any other diagnosis regardless of
      prognosis. Therefore, the present study examined the efficacy of a stress
      reduction intervention for women with breast cancer. METHODS: As part of a
      larger, randomized, controlled study of the effects on measures of stress of a
      mindfulness-based stress reduction (MBSR) intervention for women with breast
      cancer, the current analyses examined the effects on sleep complaints. RESULTS:
      Analyses of the data indicated that both MBSR and a free choice (FC) control
      condition produced significant improvement on daily diary sleep quality measures
      though neither showed significant improvement on sleep-efficiency. Participants
      in the MBSR who reported greater mindfulness practice improved significantly more
      on the sleep quality measure most strongly associated with distress. CONCLUSION:
      MBSR appears to be a promising intervention to improve the quality of sleep in
      woman with breast cancer whose sleep complaints are due to stress.

PMID- 12505560
TI  - Is there a need for another sleep journal?
AB  - OBJECTIVES: A new sleep journal, Behavioral Sleep Medicine (BSM), will publish
      its first issue shortly. This journal is interested in the application of
      behavioral/cognitive science to the study of normal and disordered sleep. I
      review the historical background leading to the creation of this journal and then
      focus on the justification for starting this journal. METHODS: The justification
      is mainly based on the availability and distribution of behavioral sleep medicine
      (bsm) research. We conducted a content analysis of sleep and nonsleep journals.
      RESULTS: We found that 17% of articles published in mainstream sleep journals
      relate to bsm. Most (75%) of the bsm literature is distributed among a large
      number of nonsleep journals, detracting from the visibility of bsm. CONCLUSION:
      BSM is needed to provide a focal point for this large but dispersed literature.
      Those who prize the field of bsm covet the aspiration that the journal will serve
      as a beacon stimulating clinical interest and scientific progress in this area.

PMID- 12505562
TI  - Efficacy and safety of minimal dose (< or =1,000 units) unfractionated heparin
      with abciximab in percutaneous coronary intervention.
AB  - Abciximab decreases adverse cardiac ischemic events, and in some subgroups,
      decreases the need for revascularization after percutaneous coronary intervention
      (PCI). However, abciximab may cause bleeding complications and thrombocytopenia
      after PCI. We hypothesized that the efficacy and safety of PCI would be
      maintained, if not improved, when performed using abciximab accompanied by only
      minimal doses (< or =1,000 U) of unfractionated heparin. In this prospectively
      designed observational study, we assessed 500 consecutive patients who underwent
      PCI, consisting of either stent deployment or high-speed rotational atherectomy,
      and who received abciximab accompanied by only a minimal dose of unfractionated
      heparin, as directed by a novel dosing strategy: (1) if the patient was
      previously receiving an infusion of heparin, then it was terminated upon arrival
      to the cardiac catheterization laboratory, and no further heparin was
      administered; or (2) if the patient was not receiving an infusion of heparin,
      then a single bolus infusion of 1,000 U was administered after establishment of
      vascular access. The median activated clotting time for the patients during PCI
      was 168 seconds (25% quartiles, 153 to 185). The technical success rate was
      99.8%. There were no major adverse clinical events during the 24 hours after PCI.
      The incidence of non-Q-wave myocardial infarction was 1.6%. The incidences of
      major and minor bleeding complications were 0.2% and 3.6%, respectively, and the
      incidence of thrombocytopenia was 2.2%. During the 30 days after PCI, there was 1
      major adverse clinical event (0.2%). During the 1 year after PCI, among the
      remaining patients, there were 92 adverse events (18.4%). We conclude that, in
      the context of historical data, the efficacy and safety of PCI using either stent
      deployment or high-speed rotational atherectomy is maintained, if not improved,
      when performed using abciximab accompanied by only minimal doses of
      unfractionated heparin.

PMID- 12505563
TI  - Impact of deep vessel wall injury on acute response and remodeling of coronary
      artery segments after cutting balloon angioplasty.
AB  - Deep vessel wall injury is believed to affect vessel dimension following coronary
      intervention. The cutting balloon is designed to treat coronary artery stenoses
      with dilatation and surgical incisions, thereby reducing excess vessel injury.
      This study examines the effect of deep vessel wall injury on acute and late
      coronary arterial response after cutting balloon angioplasty. Serial volumetric
      intravascular ultrasound (IVUS) analyses were performed in 63 lesions treated
      with cutting balloon angioplasty alone. Before intervention, the longitudinal
      range of the lesion segment that included the smallest lumen area (LA) was
      determined as LA <4 mm(2) and/or LA stenosis >60%. The exact corresponding site
      at postintervention and follow-up was aligned using peri- and intravascular
      landmarks. Average vessel area (VA), plaque area (PA), and LA were measured.
      Lesion segments were categorized as with or without deep vessel wall injury,
      which was defined as the presence of plaque/vessel wall fracture extending to the
      sonolucent (medial) layer. Before intervention, the lesion vessel size of deep
      injury group was smaller than that of the nondeep injury group (p <0.05 for
      average VA and PA), whereas average lesion LA, lesion length, and reference
      vessel size did not differ. Immediately after cutting balloon angioplasty, the
      deep injury group showed a significant increase in VA (p <0.0001) and a lesser
      decrease in PA (p <0.01) compared with the nondeep injury group. During follow
      up, the increase of VA tended to be greater in the deep injury group than in the
      nondeep injury group (p = 0.06), whereas the change of PA did not differ.
      Consequently, LA decrease was less in the deep injury group than in the nondeep
      injury group (p <0.05). From these results, it is suggested that deep vessel wall
      injury tends to occur in lesions with relatively small size and such lesions show
      favorable vessel response after cutting balloon angioplasty.

PMID- 12505564
TI  - Long-term (three-year) outcomes after stenting of unprotected left main coronary
      artery stenosis in patients with normal left ventricular function.
AB  - The purpose of this study was to analyze long-term follow-up information from
      patients treated with stenting for unprotected left main coronary artery (LMCA)
      stenosis. Stenting of unprotected LMCA stenosis is often performed in selected
      patients, but the long-term safety of this therapy is not yet established.
      Between January 1995 and September 2000, 270 consecutive patients with
      unprotected LMCA stenosis and normal left ventricular function who underwent
      treatment at 4 clinical centers were included in this study. Data were forwarded
      to the coordinating center using a standard case report form. The procedural
      success rate was 98.9%. There were no deaths, 3 stent thromboses, and 3 Q-wave
      myocardial infarctions during the hospitalization. Angiographic follow-up was
      performed in 237 patients (follow-up rate 87.8%), and the restenosis rate was
      21.1%. The reference size was an independent predictor of binary restenosis (odds
      ratio 0.543, 95% confidence interval 0.308 to 0.957, p = 0.03). During the follow
      up period (32.3 +/- 18.5 months), there were 20 deaths (8 cardiac, 12 noncardiac)
      and 5 nonfatal myocardial infarctions. Target and new lesion revascularizations
      were required in 45 (16.7%) and 31 (11.5%) patients, respectively. The cumulative
      probabilities free from major adverse cardiac events were 81.9 +/- 2.4%, 78.4 +/-
      2.6%, and 77.7 +/- 2.7%, respectively, at 1, 2, and 3 years. Combined coronary
      artery disease and postprocedural minimal luminal diameter were the significant
      predictors of major adverse cardiac events. Thus, the long-term prognosis of
      patients after stenting of unprotected LMCA stenosis was favorable in selected
      patients with normal left ventricular function.

PMID- 12505565
TI  - Treatment effects of eptifibatide in planned coronary stent implantation in
      patients with chronic kidney disease (ESPRIT Trial).
AB  - The role of platelet glycoprotein IIb/IIIa inhibitor therapy in patients with
      mild renal impairment is not well characterized. Our objective was to explore the
      associations of creatinine clearance (CrCl) with outcomes in a trial of
      eptifibatide therapy in patients who underwent percutaneous coronary intervention
      (PCI). We analyzed 48-hour and 30-day outcomes of patients enrolled in the
      Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy
      (ESPRIT) trial. Patients were randomly assigned to placebo or eptifibatide as an
      adjunct to stent implantation (1,755 with CrCl > or =60 ml/min and 289 with CrCl
      <60 ml/min). CrCl was calculated using the Cockcroft and Gault formula, and the
      associations of CrCl with outcomes were evaluated using logistic regression
      models. Patients with CrCl <60 ml/min were more likely to be older, women,
      hypertensive, and have a history of coronary artery bypass surgery, stroke, or
      peripheral vascular disease. The interaction of eptifibatide with CrCl had
      borderline significance for the 30-day outcome (p = 0.109). Treatment effect
      trended toward a greater magnitude in patients with lower CrCl (60 ml/min) (odds
      ratio 0.53, confidence interval 0.34 to 0.83) compared with those with higher
      CrCl (90 ml/min) (odds ratio 0.68, confidence interval 0.49 to 0.94). An
      accompanying increase in bleeding risk also was not apparent with lower CrCl. The
      treatment effect of eptifibatide is realized regardless of renal function and
      trends toward being greater in patients with mild renal impairment.

PMID- 12505566
TI  - Comparison of intracoronary gamma radiation for in-stent restenosis in saphenous
      vein grafts versus native coronary arteries.
AB  - Intracoronary gamma radiation is effective in reducing recurrent in-stent
      restenosis (ISR) involving native coronary arteries. This study compares the
      effectiveness and safety of intracoronary gamma radiation for the treatment of
      ISR in saphenous vein grafts (SVGs) versus native coronary arteries. In the
      Washington Radiation for In-Stent restenosis Trial (WRIST) series of gamma
      radiation trials, 1,142 patients with ISR (230 in SVG and 912 in native coronary
      arteries) completed 6-month clinical follow-up. All patients underwent balloon
      angioplasty, atherectomy, and/or restenting. Different ribbon lengths containing
      6 to 23 seeds of iridium-192 were used to cover lesion lengths <80 mm. The
      prescribed radiation doses were 14 or 15 Gy at 2-mm radial distance from the
      center of the source. Baseline demographics showed that patients with SVGs were
      older (65 +/- 13 vs 61 +/- 11 years, p <0.001), more likely male (79% vs 64%, p
      <0.001), had more multivessel coronary disease (81% vs 50%, p <0.001), and less
      diffuse lesions (17 +/- 10 vs 24 +/- 12 mm, p <0.001). At 6 months, event-free
      survival was similar for patients with SVG ISR and native coronary ISR (82% vs
      84%, p = 0.35). The SVG ISR population had a low rate of late total occlusion
      (4.6%) and late thrombosis (3.5%). Thus, treatment of ISR with gamma radiation in
      SVGs had similar outcome to native coronary arteries. The use of gamma radiation
      for the treatment of ISR should expand to SVGs.

PMID- 12505567
TI  - Left anterior descending coronary artery wall thickness measured by high
      frequency transthoracic and epicardial echocardiography includes adventitia.
AB  - High-frequency, 2-dimensional transthoracic echocardiography (HR-2DTTE)
      measurements of the left anterior descending (LAD) coronary artery wall thickness
      are larger than measurements obtained by intravascular ultrasound. We hypothesize
      that this difference is due to inclusion of the third vascular layer, which may
      represent adventitia by HR-2DTTE, and that this layer must be increasing in
      thickness with the development of atherosclerosis. We evaluated the contribution
      of this third layer to the wall thickness of the normal and atherosclerotic LAD
      artery imaged by HR-2DTTE using high-frequency epicardial echocardiography (HFEE)
      as the reference standard. Eighteen patients (10 men, mean age 62 years), 13 with
      coronary atherosclerosis and 5 with normal coronary arteries, referred for open
      heart surgery, underwent preoperative HR-2DTTE evaluation of the LAD artery
      (SONOS 5500; 3- to 8-MHz transducer) and intraoperative HFEE of the LAD artery
      (SONOS 5500; 6- to 15-MHz transducer). Wall thickness was greater in patients
      with coronary atherosclerosis than in those with normal coronary arteries by both
      HR-2DTTE (1.9 +/- 0.3 vs 1.0 +/- 0.1 mm, p = <0.001) and HFEE (1.8 +/- 0.2 vs 1.0
      +/- 0.2 mm, p = <0.001). On HFEE, the average intima plus media thickness was
      greater in patients with coronary atherosclerosis than in those with normal
      coronary arteries (0.78 +/- 0.3 vs 0.34 +/- 0.1 mm, p = 0.005). The average
      thickness of adventitia was also greater in patients with coronary
      atherosclerosis than in those with normal coronary arteries (0.92 +/- 0.2 vs 0.54
      +/- 0.2 mm, p = 0.0005). HR-2DTTE and HFEE measurements of the wall thickness
      correlated well (r = 0.83 [reader 1], p <0.001; r = 0.61 [reader 2], p <0.01). A
      third vascular layer, which likely included adventitia, represents a significant
      portion of the LAD wall thickness imaged by HR-2DTTE and HFEE, and it
      significantly increases in thickness with the development of atherosclerosis.

PMID- 12505568
TI  - Comparative effects of rosuvastatin and atorvastatin across their dose ranges in
      patients with hypercholesterolemia and without active arterial disease.
AB  - The lipid-lowering effects of rosuvastatin and atorvastatin were determined
      across their dose ranges in a 6-week, randomized, double-blind trial. Three
      hundred seventy-four hypercholesterolemic patients with fasting low-density
      lipoprotein (LDL) cholesterol > or =160 but <250 mg/dl (> or =4.14 but <6.47
      mmol/L) and fasting triglycerides <400 mg/dl (<4.52 mmol/L) and without active
      arterial disease within 3 months of entry received once-daily rosuvastatin (5,
      10, 20, 40, or 80 mg [n = 209]) or atorvastatin (10, 20, 40, or 80 mg [n = 165]).
      The percentage decrease in plasma LDL cholesterol versus dose was log-linear for
      each drug, ranging from -46.6% to -61.9% for rosuvastatin 10 and 80 mg, compared
      with -38.2% to -53.5% for atorvastatin 10 and 80 mg. The dose curve for
      rosuvastatin yielded an 8.4% greater decrease in LDL cholesterol compared with
      atorvastatin at any given dose (p <0.001). Similarly greater decreases were
      observed for rosuvastatin across the dose range in total cholesterol (-4.9%), non
      high-density lipoprotein (non-HDL) cholesterol (-7.0%), apolipoprotein B (-6.3%),
      and related ratios versus atorvastatin (all p <0.001). Because dose responses for
      HDL cholesterol, triglycerides, and apolipoprotein A-I were non-log-linear and
      nonparallel between the 2 drugs, percentage changes from baseline were compared
      at each dose. Significantly greater increases for rosuvastatin compared with
      atorvastatin were observed for HDL cholesterol at 40 and 80 mg, and for
      apolipoprotein A-I at 80 mg. Significantly greater triglyceride decreases were
      seen at 80 mg with atorvastatin over rosuvastatin. Both rosuvastatin and
      atorvastatin were well tolerated over 6 weeks.

PMID- 12505569
TI  - Comparison of the effects of atorvastatin versus simvastatin on subclinical
      atherosclerosis in primary preventionas determined by electronbeam tomography.
AB  - This study was designed to evaluate the effects of lipid-lowering therapy by
      atorvastatin versus simvastatin on calcified plaque progression, as determined by
      serial electron beam tomography (EBT), in primary prevention patients. In this
      observational study, serial EBT was performed before and after 1.2 years of
      atorvastatin (n = 103) and simavastatin therapy (n = 46); approximately 50% of
      each group was on niacin as well, in similar doses. There were no differences in
      demographic parameters between the groups. Total, low-density lipoprotein (LDL),
      and non-high-density lipoprotein (HDL) cholesterol were significantly higher in
      the atorvastatin group before treatment. Before treatment, EBT calcium score and
      volume scores were 469 and 378, respectively, in the atorvastatin patients, and
      388 and 307, respectively, in the simvastatin patients (p = NS, atorvastatin vs
      simvastatin). After treatment, there were no differences in any lipid or EBT
      values between the groups. Post-treatment total cholesterol and LDL cholesterol
      were 156 and 79 mg/dl, respectively, in the atorvastatin cohort and 154 and 76
      mg/dl, respectively, in the simvastatin group (p = NS). Calcium score and volume
      progressed 10.8%/year and 8.5%/year, respectively, in the atorvastatin group, and
      7.5%/year and 7.8%/year in the simvastatin group (p = NS, atorvastatin vs
      simvastatin). We conclude that aggressive treatment with atorvastatin and
      simvastatin in the primary prevention population, to similar lipid levels, is
      associated with equal progression of EBT-determined calcified plaque. This
      suggests that these hydroxymethylglutaryl coenzyme A reductase inhibitors exhibit
      a "class effect" with respect to progression of subclinical atherosclerosis.

PMID- 12505570
TI  - Mechanism of conversion of atypical right atrial flutter to atrial fibrillation.
AB  - The purpose of this study was to explore the mechanisms of conversion from
      atypical atrial flutter (AFL) to atrial fibrillation (AF), and the long-term
      results of cavotricuspid isthmus ablation in these patients. We retrospectively
      reviewed the records of 221 patients with typical AFL referred to our hospital
      for ablation. A total of 25 patients had atypical AFL, and cavotricuspid isthmus
      ablation was performed in 23 with isthmus-dependent atypical AFL, as well as in
      180 patients with typical counterclockwise and/or clockwise AFL. In all, 13
      spontaneous transitions from atypical AFL to AF were documented in 11 of 17
      patients. Before AF, a pattern of lower loop reentry was observed in 11 of 13
      patients (85%) and upper loop reentry in 3 (1 had both). Multiple early breaks
      along the tricuspid annulus during AFL were noted in 6 of 13 patients (46%).
      Among the 13 transitions, discrete atrial premature complexes before AF were
      found in 5 patients with lower loop reentry and in 1 with upper loop reentry
      (46%). In the remaining patients, a more rapid atrial rhythm was involved in the
      development of AF with a pulmonary venous focus in 2. In some cases, additional
      "breaks" in the functional line of block occurred before the development of AF.
      There was a significant increased incidence of AF (68%) in those with atypical
      AFL compared with those with typical AFL (38%) (p = 0.004). After a mean follow
      up of 28 +/- 9 months for the atypical group and 18 +/- 11 months for the typical
      group, the AF recurrence rate was similar (57% vs 48%, p = 0.4). Discrete atrial
      premature complexes or atrial tachycardia may initiate AF either directly or by
      producing further breaks in lines of functional block. Bidirectional
      cavotricuspid isthmus block is associated with cure or control of AF in
      approximately 50% of patients with AFL.

PMID- 12505571
TI  - Sympathoadrenal imbalance before neurocardiogenic syncope.
AB  - Neurocardiogenic syncope is the most common cause of acute loss of consciousness
      in adults. The present study attempted to identify neuroendocrine and hemodynamic
      changes before syncope that could therefore play a pathophysiologic role. Twenty
      five patients referred for chronic orthostatic intolerance had plasma
      catecholamines measured serially; 21 patients during tilt-table testing (evoking
      syncope in 13) and 4 others with spontaneous syncope while supine. Forearm blood
      flow was measured by impedance plethysmography. All 12 patients with blood
      sampled before tilt-induced syncope had progressive, marked increases in plasma
      epinephrine levels (mean 11 times baseline, p <0.0001) before syncope.
      Simultaneously obtained norepinephrine levels increased to a much smaller extent
      than did epinephrine levels ("sympathoadrenal imbalance"). In the same patients,
      forearm vascular resistance decreased by 21% before syncope. Proportionate
      changes in forearm vascular resistance before syncope correlated negatively with
      those in the epinephrine:norepinephrine ratio (r = -0.75, p = 0.005). Patients
      without syncope had forearm vasoconstriction and no sympathoadrenal imbalance
      during tilt. Patients with syncope while supine also had sympathoadrenal
      imbalance before loss of consciousness. Sympathoadrenal imbalance precedes tilt
      evoked and spontaneous neurocardiogenic syncope and correlates with concurrent
      skeletal muscle vasodilation. Sympathoadrenal imbalance may contribute to
      hemodynamic derangements precipitating neurocardiogenic syncope.

PMID- 12505572
TI  - QTc-prolonging drugs and hospitalizations for cardiac arrhythmias.
AB  - Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of
      growing importance during the past few years. In this population-based study, we
      evaluated the risk for serious cardiac arrhythmias during the use of several
      noncardiac QTc-prolonging drugs in day-to-day practice, and subsequently focused
      on several specific groups of patients who could be extremely vulnerable for drug
      induced arrhythmias. We performed a case-control study in which patients (cases),
      hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared
      with their matched controls regarding current use of QTc-prolonging drugs. Odds
      ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate
      conditional logistic regression, adjusting for potential confounding factors.
      Data were obtained from the PHARMO record linkage system. We identified 501
      cases, 39 of whom used QTc-prolonging drugs. A statistically nonsignificant
      increased risk for arrhythmias (OR 1.2, 95% CI 0.8 to 1.9) was observed in
      patients who received QTc-prolonging drugs. A clearly increased risk of
      arrhythmias was, however, found in patients with a history of asthma (OR 9.9, 95%
      CI 1.0 to 100) and in patients using potassium-lowering drugs (OR 5.3, 95% CI 1.1
      to. 25.9). Our data do not suggest that there is a strong overall association
      between the use of QTc-prolonging drugs and hospitalization for cardiac
      arrhythmias in the population at large. However, there appears to be clinically
      relevant associations of patients with a history of asthma and patients taking
      potassium-lowering drugs. The use of QTc-prolonging drugs should therefore be
      either avoided or monitored closely in these specific patients.

PMID- 12505573
TI  - Abnormal left ventricular filling with increasing age reflects abnormal
      myocardial characteristics independent of ischemia or hypertrophy.
AB  - Abnormal left ventricular (LV) filling may occur with increasing age despite
      apparently normal LV size and function, and is usually attributed to LV
      hypertrophy and coronary artery disease. The purpose of this study was to
      determine whether myocardial abnormalities could be identified in 67 such
      patients (36 men, mean age 57 +/- 9 years) whose LV hypertrophy and coronary
      artery disease were excluded by dobutamine echocardiography. All patients
      underwent gray scale and color tissue Doppler imaging from 3 apical views, which
      were stored and analyzed off line. Disturbances in structure and function were
      assessed by averaging the cyclic variation of integrated backscatter, strain
      rate, and peak systolic strain from each myocardial segment. Calibrated
      integrated backscatter (corrected for pericardial backscatter intensity) was
      measured in the septum and posterior wall from the parasternal long-axis view.
      Abnormal LV filling was present in 36 subjects (54%). Subjects with and without
      abnormal LV filling had similar LV mass, but differed in age (p <0.01), cyclic
      variation (p = 0.001), strain rate (p <0.01), and peak systolic strain (p
      <0.001). Multivariate logistic regression analysis demonstrated that age (p =
      0.016) and cyclic variation (p = 0.042) were the most important determinants of
      abnormal LV filling in these apparently normal subjects.

PMID- 12505574
TI  - Diabetes and vascular disease: common links in the emerging epidemic of coronary
      artery disease.

PMID- 12505575
TI  - Relation of cyclooxygenase isoenzyme expression and coronary artery remodeling.

PMID- 12505576
TI  - Right precordial and posterior chest leads do not increase detection of positive
      response in electrocardiogram during exercise treadmill testing.

PMID- 12505577
TI  - Heart rate variability in patients with sudden unexpected cardiac arrest in
      Thailand.

PMID- 12505578
TI  - Variation in the utilization of antiarrhythmic drugs in patients with new-onset
      atrial fibrillation.

PMID- 12505579
TI  - Delayed cure despite early recurrence after pulmonary vein isolation for atrial
      fibrillation.

PMID- 12505580
TI  - Muscle sympathetic nerve traffic during spontaneous- versus adenosine-mediated
      termination of idiopathic right ventricular outflow tract tachycardia.

PMID- 12505581
TI  - Prevalence and significance of lead-related thrombi in patients with implantable
      cardioverter defibrillators.

PMID- 12505582
TI  - Outpatient prescribing of antiarrhythmic drugs from 1995 to 2000.

PMID- 12505583
TI  - Usefulness of myocardial tissue Doppler echocardiography to evaluate left
      ventricular dyssynchrony before and after biventricular pacing in patients with
      idiopathic dilated cardiomyopathy.

PMID- 12505584
TI  - Relation between cardiovascular risk factors and nonrheumatic severe calcific
      aortic stenosis among patients with a three-cuspid aortic valve.

PMID- 12505585
TI  - Progression of aortic valve sclerosis to aortic stenosis.

PMID- 12505586
TI  - Comparison of outcome of the Marfan Syndrome in patients diagnosed at age < or =6
      years versus those diagnosed at >6 years of age.

PMID- 12505587
TI  - Effect of catheter device closure of atrial septal defect on diastolic mitral
      annular motion.

PMID- 12505588
TI  - Association of diabetes mellitus with abnormal heart rate recovery in patients
      without known coronary artery disease.

PMID- 12505589
TI  - Noninvasive assessment of nitrate tolerance using mitral Doppler and brachial
      artery ultrasonography.

PMID- 12505590
TI  - Effects of treadmill exercise on mitral inflow and annular velocities in healthy
      adults.

PMID- 12505591
TI  - Neurobiology of atypical presentations among medicare beneficiaries with unstable
      angina pectoris.

PMID- 12505592
TI  - Coagulation factor polymorphisms and sudden cardiac death.

PMID- 12505593
TI  - Seasonal variation of myocardial infarct size.

PMID- 12505594
TI  - Weekly paclitaxel.

PMID- 12505595
TI  - Weekly administration of paclitaxel: theoretical and clinical basis.
AB  - The rationale for weekly administration of paclitaxel, which acts on microtubules
      to arrest mitosis, is that more frequent delivery of moderate doses may achieve
      greater efficacy than standard doses every 3 weeks, through more sustained
      exposure of dividing tumor cells to its cytotoxic effects. This dose-dense
      approach to treatment may inhibit tumor regrowth between cycles and limit the
      emergence of malignant cell populations resistant to chemotherapy. More frequent
      exposure to paclitaxel may also enhance its apoptotic and antiangiogenic effects.
      Paclitaxel activity is considered to be independent of p53 status, in contrast to
      anticancer drugs that produce lesions on DNA, which achieve a better response if
      p53 is functional. Weekly therapy also has advantages in terms of improving
      paclitaxel therapeutic index. Clinical studies show that weekly paclitaxel is
      effective and that toxicity is acceptable. The response rates of single-agent
      paclitaxel varied from 21 to 86% in breast cancer, from 20% to 65% in ovarian
      cancer and from 30% to 56% in non-small cell lung cancer.

PMID- 12505596
TI  - Weekly paclitaxel: an effective and well-tolerated treatment in patients with
      advanced breast cancer.
AB  - The rationale for dose-dense weekly paclitaxel in the treatment of breast cancer
      is that more frequent delivery of more moderate doses may achieve greater
      efficacy than larger doses given less often through more sustained exposure of
      dividing tumor cells to cytotoxic drugs. Weekly paclitaxel has been used
      successfully in the treatment of advanced breast cancer, as single-agent therapy,
      in combination chemotherapy, with radiotherapy and with immunomodulating drugs,
      such as trastuzumab. Many of the patients in these studies have received previous
      chemotherapy regimens. Nevertheless, response rates with weekly paclitaxel up to
      86% have been achieved with single-agent therapy, up to 87% with combination
      therapy and up to 100% when combined with radiotherapy. Paclitaxel given weekly
      together with the humanized monoclonal antibody against HER2, trastuzumab, has
      shown response rates of 50-82% in patients with aggressive HER2-positive tumors.
      Paclitaxel is associated with moderate toxicity. Its main dose-limiting
      toxicities are neutropenia and peripheral neuropathy, but these are generally
      manageable.

PMID- 12505597
TI  - Weekly paclitaxel in the treatment of metastatic and/or recurrent non-small cell
      lung cancer.
AB  - Weekly paclitaxel was initially used to exploit the radiosensitizing properties
      of the drug. However, the observed improvement in therapeutic index with this
      regimen encouraged further use of weekly regimens, with and without radiotherapy,
      as a single-agent or in combination with other regimens. Single-agent weekly
      paclitaxel, at doses ranging from 50 to 200 mg/m(2)/week, has been associated
      with response rates of 23-56% with acceptable toxicity. Weekly paclitaxel has
      also been combined with carboplatin and vinorelbine in two-drug combinations and
      with cisplatin plus gemcitabine and cisplatin plus vinorelbine in three-drug
      regimens. Response rates with weekly paclitaxel in combination chemotherapy have
      ranged from 16 to 71%. Paclitaxel is particularly suited to combined modality
      therapy with radiation in non-small cell lung cancer, because of its modest
      toxicity profile, significant antineoplastic activity, ease of administration and
      potential for radiosensitization. Studies of weekly paclitaxel given together
      with radiotherapy, with or without carboplatin, have produced response rates of
      71-86% with median survival durations of 17-20.5 months.

PMID- 12505598
TI  - Role of weekly paclitaxel in the treatment of advanced ovarian cancer.
AB  - Dose-dense weekly administration of paclitaxel has the potential advantage of
      allowing a larger percentage of cancer cells to enter the vulnerable phase of
      their cell cycle when cytotoxic paclitaxel concentrations are present. The lower
      doses and shorter infusion times used with weekly dosing should also minimize
      bone marrow suppression and other toxicities associated with standard paclitaxel
      3-weekly administration. Clinical studies have confirmed that paclitaxel can be
      safely delivered on a weekly schedule as a 1-h infusion to patients with advanced
      ovarian cancer. Weekly administration of paclitaxel also appears to be better
      tolerated than 3-weekly administration. Single-agent weekly paclitaxel is
      associated with response rates of 20-65%. Combination therapy with weekly
      paclitaxel has mainly involved carboplatin and response rates with such regimens
      range from 60-88%. Triple-drug combination therapy has produced response rates of
      42-67.5%. Such therapy has included weekly paclitaxel in combination with
      carboplatin/cisplatin plus topotecan, and carboplatin plus doxorubicin. In an
      attempt to avoid problems with high corticosteroid doses, dexamethasone doses of
      10 and 8 mg have been used successfully in premedication regimens for weekly
      paclitaxel in ovarian cancer.

PMID- 12505599
TI  - Paired and unpaired features can be equally effective in human depth perception.
AB  - The horizontal separation of the eyes results in the projection of slightly
      different images in each eye that are used to recover depth. One source of depth
      information is disparity, the relative position of paired features in the two
      eyes. Another source of depth information comes from features that are present in
      only one eye's view. These unpaired features arise from occlusion and by
      definition cannot generate a conventional disparity signal. Here we compare the
      depth signals generated by paired and unpaired features using stimuli that differ
      only in whether a given feature (a vertical gap) is paired or unpaired.
      Ecologically, both stimuli are consistent with two panels separated in depth at
      the gap, but only the paired gap provides a conventional disparity signal. We
      found strikingly that depth thresholds for the two gap conditions were the same
      and that there was perfect cross-adaptation of perceived depth from the unpaired
      to paired condition, strongly suggesting a common mechanism.

PMID- 12505600
TI  - Feature-specific electrophysiological correlates of texture segregation.
AB  - Discrimination between a figure and its surround is an important first step of
      pattern recognition. This discrimination usually relies, as a first step, on the
      detection of borders between a figure and its surround, for example based on
      spatial gradients in luminance, colour, or texture. There is evidence that
      neurones in the visual cortex are specifically activated by segregation between
      textures, but the relation between segregation based on different types of
      features such as colour, luminance, and motion is unclear. Evoked EEG potentials
      specific to texture segregation were investigated in 17 observers in two separate
      experiments and by means of functional magnetic resonance imaging in a separate
      study (Fahle et al., in preparation). Differences in either luminance, colour,
      line orientation, motion, or stereoscopic depth defined a checkerboard pattern.
      Patterns defined by each of these features elicited segregation-specific
      potentials. In contrast to earlier reports (Vision Research 37 (1997) 1409),
      however, we find pronounced differences between the segregation-specific
      potentials evoked through different features, especially regarding their peak
      latencies. The topographical distribution of the activity evoked reveals
      different polarities and partly specific locations for different stimulus
      features, indicating the existence of different processors for texture
      segregation based on different features.

PMID- 12505601
TI  - Spatio-temporal frequency characteristics of the optomotor response in zebrafish.
AB  - The optomotor response (OMR) is a simple experimental paradigm that is widely
      used in the study of visual system functions. In the current paper we
      investigated how spatial and temporal properties of repetitive stimuli determine
      the OMR in zebrafish. The experiments showed that the OMR has the temporal
      characteristic of a low-pass filter when the spatial frequencies are low and of a
      band-pass filter when the spatial frequencies are high. These findings are
      discussed on the basis of inherent sampling constraints of any motion detector.
      We found some indications that the strength and direction of the OMR vary with
      the spatio-temporal frequency of the stimulus pattern as has previously been
      described for other species.

PMID- 12505602
TI  - Multiple photopigments from the Mexican blind cavefish, Astyanax fasciatus: a
      microspectrophotometric study.
AB  - The cave-dwelling (hypogean) form of the teleost Astyanax fasciatus is blind,
      having only subdermal eye rudiments, but nevertheless maintains intact opsin
      genes. Second generation offspring of a cross between these and the normally
      sighted surface (epigean) form inherit opsin genes from both ancestries. A study
      of the expressed hypogean opsins of the hybrids, in comparison to the epigean
      forms, was undertaken by microspectrophotometry. The hybrid population showed
      considerable variation in the visual pigments of double cones, with evidence for
      two groups of cells with lambda(max) intermediate to those of the epigean
      pigments. Possible explanations for these intermediate pigments are discussed,
      including the hypothesis that they may represent hybrid genes similar to the
      genes for anomalous cone pigments in humans. Evidence was also found for
      ultraviolet-sensitive single cones and for an additional MWS pigment.

PMID- 12505603
TI  - The watercolor effect: a new principle of grouping and figure-ground
      organization.
AB  - The watercolor effect is perceived when a dark (e.g., purple) contour is flanked
      by a lighter chromatic contour (e.g., orange). Under these conditions, the
      lighter color will assimilate over the entire enclosed area. This filling-in
      determines figure-ground organization when it is pitted against the classical
      Gestalt factors of proximity, good continuation, closure, symmetry, convexity, as
      well as amodal completion, and past experience. When it is combined with a given
      Gestalt factor, the resulting effect on figure-ground organization is stronger
      than for each factor alone. When the watercolor effect is induced by a dark red
      edge instead of an orange edge, its figural strength is reduced, but still
      stronger than without it. Finally, when a uniform surface is filled physically
      using the color of the orange fringe, figure-ground organization is not different
      from that for the purple contour only. These findings show that the watercolor
      effect induced by the edge could be an independent factor, different from the
      classical Gestalt factors of figure-ground organization.

PMID- 12505604
TI  - The distribution of preferred orientations in the peripheral visual field.
AB  - Orientation discrimination was measured for line targets in the fovea and in
      locations along four meridians (vertical, horizontal, 45 degrees and 135 degrees
      ) in the peripheral visual field. In all locations, the performance for vertical
      and horizontal contours was on average almost twice as good as for oblique ones.
      In addition, especially in peripheral locations along oblique meridians,
      thresholds tend to be better for radially-oriented contours compared to
      tangential ones. These effects are robust to length of the test lines and to
      small changes in position and cannot therefore be due to cortical singularities
      (pinwheels). The results suggest that the advantage of horizontal and vertical
      contours, as well as possibly of radial ones, is a manifestation of a
      characteristic structural property of the organization of the visual pathway.

PMID- 12505605
TI  - Exogenously cued attention triggers competitive selection of surfaces.
AB  - It has been reported that when an endogenous cue directs attention to a brief
      translation of one of two superimposed surfaces, observers reliably report the
      direction of that translation as well as the direction of a second translation of
      the cued surface. In contrast, if the uncued surface translates second, direction
      judgments are severely impaired for several hundred milliseconds. We replicated
      this result, but found that the impairment survived the removal of the endogenous
      cue. The impairment is therefore not due to endogenously cued attention. Instead,
      a brief translation of one surface acts as an exogenous cue that triggers an
      automatic selection mechanism, which suppresses processing of the other surface.
      This study provides a clear case of exogenous cueing of surface-based attention.
      We relate these results to identified competitive selection mechanisms in visual
      cortex.

PMID- 12505606
TI  - Orientation of Listing's plane during static tilt in young and older human
      subjects.
AB  - Three-dimensional eye positions, when expressed as rotation vectors, are
      constrained to lie in a head-fixed Listing's plane. The offset and orientation of
      Listing's plane changes when the head is tilted. To assess the influence of age
      on this phenomenon, young (less than 30 years old) and older (>65 years old)
      human subjects were seated upright, pitched nose up and nose down, and rolled
      right ear down and left ear down. Listing's plane was computed from eye movements
      recorded using a dual scleral search coil while subjects scanned a complex visual
      scene. During pitch, Listing's plane counterpitched with respect to the head,
      while during roll, it translated in a manner consistent with "ocular
      counterrolling". There was no significant difference in this reorientation of
      Listing's plane between the young and older subjects. The only obvious difference
      between the two age groups was that the "thickness" of Listing's plane was
      greater in the older subjects. This suggests that aging has a small, but
      definite, influence on Listing's law.

PMID- 12505607
TI  - Children's pursuit eye movements: a developmental study.
AB  - We examined the pursuit eye movements of adults and three groups of children 4-6,
      8-10, 12-16 years of age. The first experiment compared tracking performance of a
      partially occluded target with that of a fully visible target. The second
      experiment examined pursuit abilities of children using a non-cognitive source of
      information for motion, i.e., proprioception. In this experiment, we compared the
      ability to track one's own strobe-illuminated finger with the tracking of the
      experimenter's finger. In the first experiment, only children 4-6 years of age
      had difficulty inhibiting the tendency to look towards the visible portion of the
      partially occluded target. They also had significantly fewer epochs of pursuit
      relative to teenagers and adults. The older children's pursuit eye movements (8
      10) were neither significantly different from the youngest nor from the two older
      groups. In the second experiment, all participants pursued their own finger
      better than the experimenter's finger, but the youngest children had
      significantly fewer epochs of pursuit relative to adults. Pursuit of a partially
      occluded target and incorporation of proprioceptive signals to drive smooth
      pursuit eye movements are abilities present at four years of age that continue to
      develop with increasing age.

PMID- 12505608
TI  - A physiological theory of depth perception from vertical disparity.
AB  - It has been known since the time of Helmholtz that vertical differences between
      the two retinal images can generate depth perception. Although many ecologically
      and geometrically inspired theories have been proposed, the neural mechanisms
      underlying the phenomenon remain elusive. Here we propose a new theory for depth
      perception from vertical disparity based on the oriented binocular receptive
      fields of visual cortical cells and on the radial bias of the preferred
      orientation distribution in the cortex. The theory suggests that oriented cells
      may treat a vertical disparity as a weaker, equivalent horizontal disparity. It
      explains the induced effect, and the quadrant and size dependence of vertical
      disparity. It predicts that horizontal and vertical disparities should locally
      enhance or cancel each other according to their depth signs, and that the effect
      of vertical disparity should be orientation dependent. These predictions were
      confirmed through psychophysical experiments.

PMID- 12505609
TI  - Short-wavelength acuity: optical factors affecting detection and resolution of
      blue-yellow sinusoidal gratings in foveal and peripheral vision.
AB  - Previous studies have indicated that peripheral achromatic grating resolution is
      limited by the sampling density of the neural array (sampling limited), and
      largely unaffected by large amounts of optical defocus and significant changes in
      luminance. Under certain conditions, peripheral short-wavelength sensitive (SWS)
      grating acuity is also sampling limited. We wished to determine how the sampling
      limited nature of SWS-driven grating resolution was affected by changing optical
      defocus and stimulus luminance. Using SWS-cone isolation techniques, detection
      and resolution acuity were measured for sinusoidal gratings under varying levels
      of stimulus mean luminance and optical defocus in the fovea and at 20 degrees
      eccentricity. From 1.4 down to 0.3 cd/m(2) peripheral detection acuity was
      superior to resolution acuity, accompanied by observations of aliasing: there was
      little change in resolution performance throughout this range. For defocus up to
      3-4 dioptres, peripheral detection acuity was superior to resolution but fell
      steadily: resolution performance remained flat throughout the same range. Unlike
      achromatic acuity, foveal resolution performance displayed some robustness to
      defocus but to a lesser degree than the periphery. Peripheral SWS-driven
      resolution remains sampling limited for large changes in stimulus luminance and
      optical defocus, and should thus be useful as a clinical test of SWS-driven
      ganglion cell density.

PMID- 12505610
TI  - Short-wavelength acuity: blue-yellow and achromatic resolution loss with age.
AB  - Previous studies have indicated that peripheral resolution for achromatic
      gratings is sampling limited and directly related to the density of the
      underlying midget ganglion cell population. Previous studies by the authors have
      shown that peripheral resolution for blue-cone isolating gratings is also
      sampling limited, is robust to optical defocus and short-wavelength attenuation,
      and yields estimates of sampling density which correspond closely with the
      density of small bistratified ganglion cells. We measured peripheral resolution
      in a group of normal subjects ranging in age from 12 to 72 years, using both
      achromatic and blue-cone isolating gratings, to determine how performance (and
      hence ganglion cell density) changed with age for both systems. Resolution was
      higher for achromatic than blue-yellow gratings and performance was flat for both
      until the fifth decade. After this, performance declined for both at a rate of
      approximately 14%/decade with no significant difference between the two rates of
      decline. Individual measurements of lens density were not correlated with short
      wavelength sensitive resolution performance in the older subjects, further
      indicating that the decline in resolution was not attributable to pre-retinal
      absorption.

PMID- 12505611
TI  - Human chorionic gonadotropin/luteinizing hormone receptor expression in the adult
      rat spinal cord.
AB  - The adult and fetal rat brain contains human chorionic gonadotropin/luteinizing
      hormone (hCG/LH) receptors, that are functional in mediating the neurotropic,
      neuroendocrine and behavioral actions of gonadotropins. We hypothesized that the
      spinal cord also contains these receptors. We have now demonstrated by in situ
      hybridization, immunohistochemistry, and topical autoradiography that the adult
      rat spinal cord expresses hCG/LH receptors. Positive cells included motoneurons,
      interneurons and/or glia in the intermediate and ventral gray matter,
      interneurons and/or glia in the dorsal gray matter, and oligodendrocytes or
      astrocytes in the white matter. The receptors were able to bind an appropriate
      ligand, (125)I-hCG. The functional significance of these receptors in the spinal
      cord is unknown, but we can speculate that they may be neurotrophic in function.

PMID- 12505612
TI  - Leptin phase-advances the rat suprachiasmatic circadian clock in vitro.
AB  - The suprachiasmatic nucleus (SCN) controls circadian rhythms in mammals. The SCN
      may also participate in regulating body metabolism and energy. Similar to other
      hypothalamic nuclei, the SCN have been reported to contain glucose-sensitive
      neurons and receptors for the adipose tissue hormone, leptin. Here we
      investigated leptin effects on the SCN clock. Our results demonstrate that the
      SCN circadian clock, when isolated in vitro, can be phase advanced by leptin in a
      dose-dependent fashion that does not require non-SCN hypothalamic tissue. Phase
      advances are induced at all circadian times except late subjective night. These
      data suggest that peripheral signals of energy and metabolism directly modulate
      the circadian pacemaker in mammals.

PMID- 12505613
TI  - Understanding the dynamics of Spinocerebellar Ataxia 8 (SCA8) locus through a
      comparative genetic approach in humans and apes.
AB  - Spinocerebellar Ataxia 8 (SCA8) is a neurodegenerative disorder caused by
      expansion of a trinucleotide repeat. We undertake a comparative genetic analysis
      among human populations and primate species in the normal variation range, where
      forces that shaped present diversity can be recognised. We determinate number of
      repeats of the short tandem repeat through allele length sizing and sequencing
      methods. Human allele distributions are very similar among populations, ruling
      out ethnicity as a genetic risk for allele expansion. Primate comparison shows
      human-specific features, with longer human alleles due to a novel variable
      trinucleotide repeat, not present in non-human primates, which increased the
      disease-causing expansion likelihood. SCA8 seems to be a human specific disease.

PMID- 12505614
TI  - Effects of acute and repeated daily exposure to hypergravity on spatial learning
      in mice.
AB  - Studies in humans have revealed that exposure to altered gravity may lead to
      impairments in cognitive functions. The objective of this study was to test
      whether mice exposed to hypergravity using a centrifuge apparatus showed learning
      impairments in a spatial learning task. Mice rotating at 1G or at 2G acceleration
      gravity and non-rotating controls were tested for reactivity to a spatial change
      after either a single 1 h or five repeated 1 h daily rotations in the centrifuge.
      While no differences among groups were found in the performance after single
      exposure to altered gravity, 5 days of repeated exposures to 1G or 2G gravity
      conditions significantly affected mouse ability to discriminate a new spatial
      arrangement. Additionally, this effect was stronger in the animals repeatedly
      exposed to 2G rather than to 1G conditions.

PMID- 12505615
TI  - Crossmodal temporal processing acuity impairment aggravates with age in
      developmental dyslexia.
AB  - Temporal processing has been found to be impaired in developmental dyslexia. We
      investigated how aging affects crossmodal temporal processing impairment with 39
      dyslexic and 40 fluent 20-59-year-old readers. Cognitive temporal acuity was
      measured at millisecond levels in six tasks. They consisted of order judgments of
      two brief non-speech stimulus pulses, the stimuli being audiotactile,
      visuotactile and audiovisual, and of simultaneity/nonsimultaneity detection of
      the pulses in two parallel three-pulse trains. Temporal acuity declined with age
      in both reading groups and its impairment was observed in developmental dyslexia.
      A new finding was that the crossmodal temporal impairment, directly relevant to
      reading, increased with age. The age-related exacerbation suggests a
      developmental neuronal deficit, possibly related to magnocells, which exists
      before dyslexia and is its ontogenetic cause.

PMID- 12505616
TI  - Phosphorylation of alpha-synuclein characteristic of synucleinopathy lesions is
      recapitulated in alpha-synuclein transgenic Drosophila.
AB  - alpha-Synuclein is a major component of Lewy bodies in the brains of patients
      with Parkinson's disease (PD) as well as of neuronal/glial inclusions in a subset
      of neurodegenerative disorders collectively termed synucleinopathies. Here we
      studied by immunohistochemistry the accumulation of alpha-synuclein in transgenic
      (TG) Drosophila overexpressing wild-type (WT) or familial PD-linked mutant (i.e.
      A30P and A53T) alpha-synuclein in neurons, with special reference to the
      phosphorylation at Ser129, that is characteristic of human synucleinopathy
      lesions. Progressive accumulation of human alpha-synuclein was widely observed in
      the cell bodies and neurites of major neuronal nuclei in TG Drosophila brains,
      and phosphorylation of alpha-synuclein at Ser129 was detected in a limited subset
      of neurons approximately 1 week after alpha-synuclein immunoreactivity was first
      detected. Phosphorylated alpha-synuclein was most abundant in A53T mutant,
      followed by A30P and WT Drosophila. These results suggest that accumulation and
      phosphorylation of alpha-synuclein is recapitulated in neurons of alpha-synuclein
      transgenic Drosophila, that underscores the relevance of this model to human
      synucleinopatheis.

PMID- 12505617
TI  - Copper-dependent generation of hydrogen peroxide from the toxic prion protein
      fragment PrP106-126.
AB  - Oligomeric forms of many of the aggregating proteins associated with
      neurodegenerative diseases are toxic to cultured cells. We have shown recently
      that Abeta and alpha-synuclein can both induce the formation of hydroxyl radicals
      following incubation in solution, upon the addition of Fe(II). Thus, they appear
      to generate hydrogen peroxide, which is converted to hydroxyl radicals via the
      Fenton reaction. Here we show that the widely studied toxic peptide fragment of
      the prion protein, PrP106-126, has exactly the same property, but only in the
      presence of copper ions. Since the aggregation and toxicity of PrP106-126 have
      been reported to be critically dependent on copper binding, our data suggest that
      the published cytotoxic effects of this peptide could also be due to its ability
      to generate hydrogen peroxide.

PMID- 12505618
TI  - DNA damage or growth factor withdrawal does not evoke activation of MYB
      transcription factors in neuronal cancer cell lines.
AB  - It has been recently observed that MYB proteins are induced in neuronal cell
      cultures exposed to DNA damaging agents or growth factor deprivation. While it
      has been proposed that MYB proteins activity is required to bring about death in
      neuronal cells subjected to apoptotic stimuli, here we show that MYB is not
      activated in differentiated pheochromocytoma-12 cells (PC12) or LAN5 cells
      exposed to the DNA damaging agent campothecin or in differentiated PC12 cells
      subjected to nerve growth factor withdrawal. We conclude that MYB activation
      cannot be generalised in terminally differentiated neuronal cancer cell lines.

PMID- 12505619
TI  - Cerebrospinal fluid S100B correlates with brain atrophy in Alzheimer's disease.
AB  - S100B is a predominantly astrocytic protein with dose-dependent cytotoxic and
      neurotrophic properties encoded on chromosome 21q22.3. Concentrations of S100B
      were measured in the cerebrospinal fluid (CSF) of 31 patients with Alzheimer's
      disease (AD), 36 patients with frontotemporal lobe dementia (FTLD) and 49
      patients with other non-inflammatory neurological diseases. Additional CSF S100B
      concentrations were correlated with normalised brain volume measurements in AD
      and FTLD. CSF S100B was significantly higher in AD (Mean+/-standard
      deviation=0.4+/-0.2 ng/ml) and FTLD (0.42+/-0.19 ng/ml) patients when compared
      with control subjects (0.25+/-0.08, P<0.001). In patients with AD, S100B
      correlated negatively with normalised brain volume (R(S)=-0.53, P<0.001). No such
      correlation was found for FTLD patients. This study supports the concept that
      S100B is of pathological relevance for degeneration of the central nervous system
      in AD.

PMID- 12505620
TI  - Different roles of group I and group II metabotropic glutamate receptors on
      phencyclidine-induced dopamine release in the rat prefrontal cortex.
AB  - The dopamine system in the limbic-prefrontal cortex has been assumed to play an
      important role in the cognitive dysfunction of schizophrenia and phencyclidine
      (PCP)-induced psychosis. In the present study, the role of metabotropic glutamate
      (mGlu) receptor subtypes on PCP-induced cortical dopamine release was
      investigated using the microdialysis technique. Infusion of 50 and 100 microM of
      non-selective mGlu receptor agonist trans-(1S,3R)-1-amino-1,3
      cyclopentanedicarboxylic acid inhibited PCP-induced dopamine release, while the
      basal dopamine level was not significantly affected. A similar inhibition of PCP
      induced dopamine release was observed with 100 and 500 microM of selective group
      I mGlu receptor agonist, (+)-3-hydroxy-phenylglycine. On the other hand, infusion
      of 10 microM of selective group II mGlu receptor agonist, 2-(2, 3
      dicarboxycyclopropyl)-glycine, enhanced the PCP-induced dopamine increase. These
      results suggest that group I and II mGlu receptors exert opposite modulations on
      the PCP-induced dopamine release.

PMID- 12505621
TI  - Sodium channel heterologous expression in mammalian cells and the role of the
      endogenous beta1-subunits.
AB  - Sodium currents in cell lines transfected with the sole alpha-subunit, or
      constitutively expressing sodium channels, have an inactivation that is always
      prevalently mono-exponential. Differently, expression of alpha-subunit in Xenopus
      oocytes exerts slow inactivating currents with biphasic decay, while simultaneous
      co-transfection of alpha and beta1 restores a mono-exponential (normal)
      inactivation. A hypothesis for such differences is that an endogenous presence of
      beta1 or beta1-alternative splicing, beta1A, in cells could account for the
      normal inactivation. To test this hypothesis and to evaluate the role for the
      beta1A, we inhibited the expression of beta1/beta1A by antisense oligonucleotides
      on Nav1.4-transfected human embryonic cell line 293 (HEK) cells. Reduction of
      beta1/beta1A produces no significant functional effects in Nav1.4-HEK. This
      result invalidates the hypothesis that the lack of slow-mode in cell lines is
      simply due to a constitutive expression of beta1/beta1A.

PMID- 12505622
TI  - Dietary oleic acid not used during brain development and in adult in rat, in
      contrast with sciatic nerve.
AB  - In order to determine exactly the effect on the nervous system of concentration
      of dietary oleic acid on the fatty acid composition of different part of the
      nervous system, triglycerides were synthesized using chemical and enzymological
      methods. The dose-effect was determined using an experimental protocol with seven
      groups of rats who received a diet in which the oleic acid level varied from 0 to
      6000 mg per 100 g diet, but the other ingredients were identical (in particular
      the essential fatty acids, linoleic and alpha-linolenic acid). Rats were fed the
      diets from two weeks before mating, and their pups were sacrificed aged either 21
      or 60 days. When the level of oleic acid in the diet was increased, the main
      modifications observed in 21-day-old deficient animals were as follows. (i). For
      18:1(n-9), in liver, plateau was reached at about 4 g oleic acid per 100 g diet.
      Below this level, the higher the dose the greater the response. In whole brain,
      brain myelin, and nerve endings (but not sciatic nerve) the oleic acid level
      remained optimal and constant whatever the level of oleic acid in the diet. (ii).
      16:1(n-7) concentration decreased in liver and in sciatic nerve, but not in
      nervous tissue. (iii). In 60-day-old animals, results were generally similar to
      those in 21-day-old animals.

PMID- 12505623
TI  - Anti-prion antibodies for prophylaxis following prion exposure in mice.
AB  - Prion disease is characterized by a conformational change of the normal form of
      the prion protein (PrP(C)) to the scrapie-associated form (PrP(Sc)). Since the
      emergence of new variant Creutzfeldt-Jakob disease a potentially large human
      population is at risk for developing prion disease. Currently, no effective
      treatment or form of post-exposure prophylaxis is available for prion disease. We
      recently showed that active immunization with recombinant PrP prolongs the
      incubation period of scrapie. Here we show that anti-PrP antibodies following
      prion exposure are effective at increasing the incubation period of the
      infection. Stimulation of the immune system is an important therapeutic target
      for the prion diseases, as well as for other neurodegenerative illnesses
      characterized by abnormal protein conformation.

PMID- 12505624
TI  - RNA extraction and RT-PCR procedures adapted for the detection of enterovirus
      sequences from frozen and paraffin-embedded formalin-fixed spinal cord samples.
AB  - Methods for detecting enterovirus RNA in both paraffin-embedded, formalin-fixed
      and frozen spinal cord sections from amyotrophic lateral sclerosis (ALS) patients
      were established. A proteinase K digestion following the deparaffinization
      procedure was required for the fixed spinal cord sections, whereas only one step
      of crushing in phosphate buffered saline was necessary for the frozen samples
      prior to the extraction of the RNA. With an optimized reverse transcription and
      PCR procedure, enterovirus RNA could be detected from frozen and fixed archival
      spinal cord samples.

PMID- 12505625
TI  - In situ PCR-associated immunohistochemistry identifies cell types harbouring the
      Maedi-Visna virus genome in tissue sections of sheep infected naturally.
AB  - Maedi-Visna virus (MVV) is a non-oncogenic ovine lentivirus whose main targets
      are the lung, mammary gland, central nervous system and joints. Cells of the
      monocyte-macrophage lineage are the major viral target in vivo; other cell types
      are infected as well, as indicated by several studies, largely based on the
      examination of animals infected experimentally or on the in vitro infection of
      cultured cells. Aim of this study was to investigate the cell types harbouring
      the viral genome in lungs and mammary glands of animals infected naturally by
      using in situ PCR-associated immunohistochemistry. Several types of cells were
      infected: in the lung type I and II pneumocytes, interstitial and alveolar
      macrophages, endothelial cells and fibroblast-like cells. Epithelial cells,
      macrophages, endothelial cells and fibroblast-like cells were infected also in
      the mammary gland. These results indicate that the in situ PCR, a powerful
      technique which combines the high sensitivity of the conventional PCR with the
      ability to localise the cellular targets within a tissue, can be improved further
      by its association with the immunohistochemistry. This can be especially
      advantageous when the presence and localisation of the target sequence are
      investigated in the context of a tissue with its complex cellular organisation.

PMID- 12505626
TI  - Evaluation of automated RT-PCR to accelerate the laboratory diagnosis of foot-and
      mouth disease virus.
AB  - Automated fluorogenic (5' nuclease probe-based) reverse transcription polymerase
      chain reaction (RT-PCR) procedures were evaluated for the diagnosis of foot-and
      mouth disease (FMD) using suspensions of vesicular epithelium, heparinised or
      clotted blood, milk and oesophageal-pharyngeal fluid ('probang') samples from the
      United Kingdom (UK) 2001 epidemic and on sera from animals experimentally
      infected with the outbreak serotype O FMD virus strain. A MagNA Pure LC was
      initially programmed to automate the nucleic acid extraction and RT procedures
      with the PCR amplification carried out manually by fluorogenic assay in a GeneAmp
      5700 Sequence Detection System. This allowed 32 samples to be tested by one
      person in a typical working day or 64 samples by two people within 10-12 h. The
      PCR amplification was later automated and a protocol developed for one person to
      complete a single test incorporating 96 RT-PCR results within 2 working days or
      for two people to do the same thing in around 12 h. The RT-PCR results were
      directly compared with those obtained by the routine diagnostic tests of ELISA
      and virus isolation in cell culture. The results on blood, probang and milk
      samples were in broad agreement between the three procedures but specific RT-PCR
      protocols for such material have to be fully optimised as perhaps have the
      positive-negative acceptance criteria. However, the automated RT-PCR achieved
      definitive diagnostic results (positive or negative) on supernatant fluids from
      first passage inoculated cell cultures and its sensitivity was greater than ELISA
      on suspensions of vesicular epithelium (ES) and at least equivalent to that of
      virus isolation in cell culture. The combined tests of ELISA, virus isolation in
      cell culture and RT-PCR might, therefore, only be required for confirmation of a
      first outbreak of FMD in a previously FMD-free country. Should a prolonged
      outbreak subsequently occur, then either ELISA plus RT-PCR or else RT-PCR alone
      could be used as the laboratory diagnostic tool(s). Either approach would
      eliminate the requirement for sample passage in cell culture and considerably
      advance the issue of laboratory diagnostic test results.

PMID- 12505627
TI  - Cytokine expression in respiratory syncytial virus-infected mice as measured by
      quantitative reverse-transcriptase PCR.
AB  - In the murine model for respiratory syncytial virus (RSV) infection, cytokine
      patterns induced by vaccinations with either killed (i.e. formalin-inactivated,
      alum-precipitated) virus (KV) or live virus (LV) have been shown to influence
      disease expression. To determine the mRNA expression of the cytokines IL-4 and
      IFN-gamma in BALB/c mice challenged with RSV, a real-time quantitative reverse
      transcriptase PCR assay was developed. This assay uses 5'-exonuclease fluorogenic
      probes and is performed on the ABI PRISM 7700 Sequence Detector System (TaqMan).
      The relative quantitative levels of mRNA for IL-4 and IFN-gamma were compared
      with those measured by an RNase protection assay (RPA) and an enzyme immunoassay
      (EIA), which are methods used to measure the levels of mRNA and protein,
      respectively. Results obtained by the TaqMan assay showed that mice primed with
      KV induces increased IL-4 mRNA production while LV induces increased IFN-gamma
      mRNA, which is in agreement with conventional methods. IL-4 and IFN-gamma
      relative quantities obtained from TaqMan were highly correlated to those
      determined by RPA (r=0.96 for IFN-gamma, P<0.01) and EIA (r=0.90 for IL-4 and
      r=0.75 for IFN-gamma, P<0.01). Assay reproducibility was examined by testing a
      same sample in triplicate at three experiments. Minimal deviation values were
      observed in both intra- and inter-assays. TaqMan, which is rapid, sensitive and
      reproducible, provides an alternative tool for the quantitative analysis of
      cytokine mRNA expression in the murine model of RSV immunopathogenesis.

PMID- 12505628
TI  - Production and characterization of monoclonal antibodies to a grouper iridovirus.
AB  - A panel of six monoclonal antibodies (mAbs) against a grouper iridovirus (SGIV)
      were produced by immunization of Balb/c mice with purified virus preparations.
      Isotyping test revealed all the mAbs were IgG1. None of the mAbs possessed the
      ability to neutralize SGIV in cell cultures. Western blot showed that 4 mAbs
      reacted with 2 SGIV proteins at molecular mass of approximately 100 and 117 kDa
      in gradient-purified virus. Immunofluorescent studies showed that the two
      specific viral proteins VP100 and VP117 were localized within virus assembly
      sites in the cytoplasm of SGIV-infected grouper cells (GP). Fractionations of the
      iridovirus in a 20-60% sucrose gradient were detected successfully by all the six
      mAbs using immunodot blot. An antigen-capture enzyme-linked immunosorbent assay
      (ELISA) system, based on the use of mAb 7E11 for capture and a rabbit polyclonal
      antibody to SGIV for detection was developed. SGIV antigen was detected in
      gradient-purified virus and virus-infected grouper blood. These novel mAbs will
      facilitate the development of more specific and standardized diagnostic
      techniques for marine fish iridovirus.

PMID- 12505629
TI  - Automatic quantitation of HIV-1 mediated cell-to-cell fusion with a digital image
      analysis system (DIAS): application for rapid screening of HIV-1 fusion
      inhibitors.
AB  - Human immunodeficiency viruses type 1 (HIV-1) mediated cell-to-cell fusion plays
      an important role in HIV-1 spread from infected cells to uninfected cells and in
      HIV-1 cytopathogenesis. In the present study, we developed a convenient cell
      fusion assay using a computer-controlled digital image analysis system (DIAS) for
      automatic quantitation. Compared with a manual quantitative method, DIAS
      automatic method is less laborious, and more rapid. Furthermore, it is more
      objective and less dependent on the researchers' experience. This method has
      great potential to be developed further as a high-throughput screening assay for
      rapid screening of HIV-1 fusion inhibitors, for evaluating the activity of HIV-1
      entry inhibitors and for studying the mechanism of action of anti-HIV-1 agents.

PMID- 12505630
TI  - A feline kidney cell line-based plaque assay for feline calicivirus, a surrogate
      for Norwalk virus.
AB  - Feline calicivirus (FCV) has been used by researchers as a surrogate for Norwalk
      virus (NV), since they share a similar genomic organization, physicochemical
      characteristics, and are grouped in the same family, Caliciviridae. Unlike NV,
      however, FCV can grow in established cell lines and produce a syncytial form of
      cytopathic effect. In this report, we describe the development and
      standardization of a plaque assay for FCV using monolayers of an established line
      of feline kidney (CrFK) cells in 12-well cell culture plates. The assay method
      has demonstrated reproducibility, ease of performance and resulted in clear
      plaque zones, readable in 24 h after virus inoculation. The infectivity titre of
      the virus by this plaque assay agreed well with tissue culture infectious
      dose(50) (TCID(50)) determinations. The described plaque assay would be a
      valuable tool in conducting various quantitative investigations using FCV as a
      model for NV and Norwalk-like viruses (NLV).

PMID- 12505631
TI  - Comparison of TaqMan real-time PCR and p24 Elisa for quantification of in vitro
      HIV-1 replication.
AB  - In this study, TaqMan PCR was used to assess viral replication of HIV-1 infected
      cells in vitro. This PCR technique was compared with p24 ELISA as a standard
      method to monitor HIV-1 replication in cell culture. Hut78 T-lymphoblastoid cells
      were infected with different titres of HIV-1(IIIb) (MOI 0.05-0.0005). The course
      of HIV-1 replication was monitored by determination of p24 concentrations by
      ELISA in cell culture supernatants and by quantitation of HIV-1 gag RNA by TaqMan
      RT-PCR. Additionally, the number of HIV-1 proviral copies was assessed by TaqMan
      PCR. Monitoring of HIV-1 replication by p24 ELISA and TaqMan RT-PCR revealed
      comparable kinetics of infection. Both methods provided similar data on the
      exponential increase and on plateauing of HIV-1 replication. Furthermore, both
      methods were equally sensitive. However, a 7 log linearity of TaqMan HIV-1 gag
      PCR was demonstrated without dilution of the specimen, in contrast to p24 ELISA,
      where because of its narrow range of detectable p24 concentrations, sample
      dilution was necessary. Although determination of the number of proviral copies
      by TaqMan PCR does not measure HIV-1 replication, the kinetics of proviral copy
      number following in vitro inoculation of cells with HIV-1 was nearly the same as
      the kinetics of HIV-1 RNA copy numbers. In conclusion, TaqMan real-time RT-PCR
      was demonstrated as a reliable and sensitive tool to quantify and monitor HIV-1
      replication in cell culture. It is suggested, therefore, that this technique be
      an alternative method to monitor HIV-1 replication in vitro.

PMID- 12505632
TI  - Detection of petunia vein-clearing virus: model for the detection of DNA viruses
      in plants with homologous endogenous pararetrovirus sequences.
AB  - A number of cases of plant virus sequence integration into host plant genome have
      been reported. In at least two cases, endogenous pararetrovirus sequences are
      correlated strongly with subsequent episomal virus infection and there is
      circumstantial evidence that this also occurs for Petunia vein-clearing virus
      (PVCV). The detection of viruses is a critical component of plant health and
      therefore, it is important to have diagnostic procedures that differentiate
      between the detection of encapsidated viral DNA and homologous sequences in the
      host genome. PCR-based detection methods targeted at PVCV DNA have been tested
      and particular attention was paid to design controls that would indicate the
      existence of host DNA in the reaction. The use of ion-exchange chromatography for
      the partial purification of plant viruses from other cellular components,
      including chromosomal DNA, is described. The methods tested for PVCV detection
      are used to illustrate general principles for the specific detection of virus
      infections in host plants that carry homologous virus sequences in their genomes.

PMID- 12505633
TI  - Tn7-mediated introduction of DNA sequences into bacmid-cloned cytomegalovirus
      genomes for rapid recombinant virus construction.
AB  - Our basic understanding of how viruses infect, replicate, and cause disease has
      been largely derived from genetic approaches in which viral sequences have been
      mutated and the consequences of those mutations determined. In the herpesvirus
      field, deletions or insertions that preclude expression of specific viral
      proteins or remove critical cis elements have been invaluable in identifying
      their overall functions. We are now ready to move to a new level of detail
      mapping functional domains within viral proteins or defining cis elements to the
      nucleotide level. This level of detail will require mutagenesis on a new scale,
      with recombinant viruses containing mutations within a given locus perhaps
      numbering in the hundreds. Mutagenesis on this scale would be greatly facilitated
      by more rapid methods of recombinant virus construction. In this report, we
      adapted a technology employing Tn7-mediated site-specific transposition [J.
      Virol. 67 (1993) 4566] as a rapid and highly reliable method to introduce novel
      sequences into bacmid-cloned herpesvirus genomes. We show that recombinant
      viruses can be rapidly created and that a deletion of the human cytomegalovirus
      (HCMV) essential gene ie2 can be complemented in cis by reintroduction, via
      transposition, of an ie2 cDNA; detailed mutagenesis of the complementing ie2 gene
      can now follow. Tn7-mediated transposition should accelerate greatly the pace at
      which recombinant herpesviruses can be constructed and, thus, facilitate the use
      of recombinant viruses for detailed mutagenic studies of both cis- and trans
      acting genetic elements.

PMID- 12505634
TI  - Improved subtractive suppression hybridization combined with high density cDNA
      array screening identifies differentially expressed viral and cellular genes.
AB  - Suppression subtractive hybridization (SSH) combines normalization and
      suppression PCR effect step in a single cycle to isolate differentially expressed
      genes in two cDNA samples. The PCR suppression effect is mediated by long
      inverted terminal repeats. The efficiency of the restriction enzyme digestion and
      the adapter ligation are crucial in the success of the SSH. We modified the
      original SSH protocol in order to improve the efficiency of the subtraction. A
      magnetic bead based separation step has been included after the ligation step, to
      purify the successfully ligated fraction of the tester. EBV(NEO) infected Akata(
      ) Burkitt's lymphoma cell line was compared with the EBV(-) Akata(-) cell line to
      isolate differentially expressed genes with the improved SSH protocol. Some 44
      cDNA clones that showed the greatest differences in expression have been
      sequenced. Of them, 20 showed more than 3-fold difference in expression. Seven of
      the 20 genes were EBV genes. To quantitate the expression levels, high density
      nylon cDNA array hybridization was optimized. Statistical analysis of the data
      revealed that the spotting of the arrayer is exceptionally reproducible, which
      makes the comparison of the hybridization of parallel filters possible.

PMID- 12505635
TI  - Establishment and characterization of two new pig cell lines for use in
      virological diagnostic laboratories.
AB  - Two pig cell lines derived from kidney and trachea tissues and referred to as
      newborn swine kidney (NSK) and newborn pig trachea (NPTr) were established
      following serial culture of primary cells. They were characterized by an
      epithelial-like morphology, high capacity to replicate and stability of the cell
      monolayer for several days after seeding. Their modal chromosome number was
      modified in comparison to that of primary swine cells and they both displayed a
      transforming potential in vitro and displayed oncogenicity in nude mice.
      Infection with pig endogenous retroviruses was detected. Almost all the swine
      viruses tested, i.e., pseudorabies virus, pig parvovirus, hog cholera virus,
      transmissible gastroenteritis virus of swine, encephalomyocarditis virus, swine
      vesicular disease virus and the enteroviruses, except pig reproductive
      respiratory syndrome virus, were capable of replicating in the new cell lines
      with titres similar to the ones detected in the reference culture systems.
      Furthermore, all the selected influenza virus sub-types isolated from human,
      swine and avian species replicated with cytopathic effect in NSK and NPTr cells,
      whereas, of all the equine influenza viruses tested only the Miami and Suffolk
      sub-types replicated.

PMID- 12505636
TI  - Identification of coronaviruses in dogs that segregate separately from the canine
      coronavirus genotype.
AB  - The genetic diversity of 16 canine coronavirus (CCoV) samples is described.
      Samples were obtained from pups infected naturally living in different areas.
      Sequence data were obtained from the M gene and pol1a and pol1b regions. The
      phylogenetic relationships among these sequences and sequences published
      previously were determined. The canine samples segregated in two separate
      clusters. Samples of the first cluster were intermingled with reference strains
      of CCoV genotype and therefore could be assigned to this genotype. The second
      cluster segregated separately from CCoV and feline coronavirus genotypes and
      therefore these samples may represent genetic outliers. The reliability of the
      classification results was confirmed by repeating the phylogenetic analysis with
      nucleotide and amino acid sequences from multiple genomic regions.

PMID- 12505637
TI  - Mixed infection of a child care provider with hepatitis A virus isolates from
      subgenotypes IA and IB revealed by heteroduplex mobility assay.
AB  - Phylogenetic analysis based on a 168 base segment encompassing the putative
      VP1/2A junction of the hepatitis A virus (HAV) genome has enabled the
      classification of HAV isolates into seven genotypes (I-VII). Genotype I, which
      includes the vast majority of the human HAV isolates, has been divided further
      into subgenotypes IA and IB. An heteroduplex mobility assay was designed with
      amplification products from the VP1/2A junction region, and used as a genotyping
      method able to discriminate HAV isolates belonging to IA, IB and non-I genotypes.
      The method was used to successfully genotype 48 samples (16 IA and 32 IB).
      However, one HAV RNA positive serum sample (AUX-23), collected from a 15 year old
      female employed at a child care center located in Rio de Janeiro, Brazil, showed
      an unusual pattern. PCR products from sample AUX-23 gave rise to heteroduplex
      bands when mixed with IA products as well as with IB products, suggesting the
      presence of HAV isolates from both subgenotypes in the serum. PCR products from
      sample AUX-23 were then cloned and 20 clones were analyzed by heteroduplex
      mobility assay. Eleven were subgenotype IA and 9 were IB. Three clones of each
      subgenotype were then sequenced to confirm the results. These data constitute the
      first report of mixed infection of a single individual with different HAV
      isolates.

PMID- 12505638
TI  - An improved method for recovering rabies virus from cloned cDNA.
AB  - A new system for recovery of rabies virus from cDNA plasmid, the transcription of
      which was driven by cellular RNA polymerase II, was developed. The plasmid
      contains full-length viral cDNA flanked by hammerhead ribozyme and hepatitis
      delta ribozyme sequences, arranged downstream of the cytomegalovirus (CMV)
      promotor. Transfection with the full-length cDNA plasmid together with helper
      plasmids encoding viral N, P, and L proteins without supply of T7 RNA polymerase
      produced a recombinant rabies virus in several cell lines. The efficiency of
      recovery between the conventional T7 promotor system and the new CMV promotor
      system was compared using these plasmid constructs. The newly established system
      is applicable to various cell lines and allows rapid and efficient generation of
      recombinant rabies virus.

PMID- 12505639
TI  - The development of a competitive PCR-ELISA for the detection of equine
      herpesvirus-1.
AB  - Equine herpesvirus-1 (EHV-1) infection is of significant animal welfare and
      economic importance. Yet, no standardised molecular techniques are available for
      diagnosis or confirmation of viral infection. The purpose of this study was to
      develop a standardised and quantitative assay system for the reliable detection
      of EHV-1 infection which was capable of eliminating the likelihood of false
      negative results. A region within the EHV-1 glycoprotein B gene was amplified by
      polymerase chain reaction (PCR), cloned and subjected to site-directed
      mutagenesis to generate a control plasmid, amplifiable by identical primers to
      wild type EHV-1, yet capable of detection by an alternate dinitrophenylated
      oligonucleotide probe in a PCR-ELISA system. A competitive PCR-ELISA system which
      can control for the presence of PCR inhibitors and which is capable of detecting
      63 genome equivalents of EHV-1 has been developed. EHV-1 presence in infected
      equine tissue and cell culture material was demonstrated using this system. The
      entire assay can be completed within one working day and facilitates multiple
      sample analysis. The availability of a robust, competitive PCR-ELISA system for
      the detection of EHV-1 will facilitate the rapid and sensitive detection of EHV-1
      and offers the potential for eliminating the occurrence of abortion storms in
      stud farms.

PMID- 12505640
TI  - A novel high throughput screening assay for HCV NS3 serine protease inhibitors.
AB  - Hepatitis C virus (HCV) infection is a major worldwide health problem, causing
      chronic hepatitis, liver cirrhosis and primary liver cancer (Hepatocellular
      carcinoma). HCV encodes a precursor polyprotein that is enzymatically cleaved to
      release the individual viral proteins. The viral non-structural proteins are
      cleaved by the HCV NS3 serine protease. NS3 is regarded currently as a potential
      target for anti-viral drugs thus specific inhibitors of its enzymatic activity
      should be of importance. A prime requisite for detailed biochemical studies of
      the protease and its potential inhibitors is the availability of a rapid reliable
      in vitro assay of enzyme activity. A novel assay for measurement of HCV NS3
      serine protease activity was developed for screening of HCV NS3 serine protease
      potential inhibitors. Recombinant NS3 serine protease was isolated and purified,
      and a fluorometric assay for NS3 proteolytic activity was developed. As an NS3
      substrate we engineered a recombinant fusion protein where a green fluorescent
      protein is linked to a cellulose-binding domain via the NS5A/B site that is
      cleavable by NS3. Cleavage of this substrate by NS3 results in emission of
      fluorescent light that is easily detected and quantitated by fluorometry. Using
      our system we identified NS3 serine protease inhibitors from extracts obtained
      from natural Indian Siddha medicinal plants. Our unique fluorometric assay is
      very sensitive and has a high throughput capacity making it suitable for
      screening of potential NS3 serine protease inhibitors.

PMID- 12505641
TI  - Development of a multiplex RT-PCR to detect transcription of varicella-zoster
      virus encoded genes.
AB  - The reverse transcription polymerase chain reaction (RT-PCR) is used commonly to
      analyse transcription of genes. In the field of virology it is an extremely
      helpful method to analyse the transcriptional activity of both, DNA and RNA
      viruses. The standard RT-PCR allows an investigation of the activity of only one
      gene. Here, we describe the development of a sensitive multiplex RT-PCR assay for
      single tube amplification to analyse a set of different genes encoded by the
      varicella-zoster virus (VZV), a member of the human-pathogenous herpesviruses.
      This multiplex RT-PCR amplifies the genes ORF 4, ORF 21 and ORF 68; each of these
      three genes belongs to a distinct class of genes, which is expressed one after
      the other within the infectious cycle. This method provides the possibility for
      rapid but extensive examination of VZV transcriptional activity and could be used
      in both fields, fundamental research as well as clinical diagnostic work.

PMID- 12505642
TI  - Detection and quantitation of Kaposi's sarcoma-associated herpesvirus (KSHV) by a
      single competitive-quantitative polymerase chain reaction.
AB  - Kaposi's sarcoma-associated herpesvirus is a novel herpesvirus linked to AIDS
      related neoplasms. Currently it is difficult to evaluate the number of virions in
      viral preparation or in samples obtained from patients with Kaposi's sarcoma
      (KS), since no protocol for determining the plaque forming units of KSHV exists.
      We constructed a fragment of a different size than the target viral DNA to carry
      out a competitive-quantitative PCR. Both fragment and viral DNA were added to a
      single PCR reaction to compete for the same set of primers. By knowing the amount
      of the competitor added to the reaction, we could determine the number of viral
      DNA molecules. We used this assay successfully to detect and quantify KSHV
      genomes from KS skin biopsies and pleural effusion lymphoma, and from different
      viral preparations. To date, this is the most convenient and economic method that
      allows an accurate and fast viral detection/quantitation with a single PCR.

PMID- 12505643
TI  - Rapid and efficient construction of recombinant bovine herpesvirus 1 genomes.
AB  - Bovine herpesvirus 1 (BoHV-1) is an important pathogen of cattle. Recombinant
      bovine herpesvirus 1 viruses (rBoHV) have been studied extensively as potential
      vaccines for BoHV-1 associated diseases. A method is described which advances
      protocols used currently for constructing rBoHV by producing recombinant viruses
      free of parent virus. The method, restriction endonuclease mediated recombination
      (REMR), utilises a unique NsiI site in the BoHV-1 genome. Following NsiI
      digestion the two genomic fragments are prevented from recombining by
      dephosphorylation. However, when the genomic fragments are co-transfected into a
      susceptible cell-line with a third DNA fragment (DNA bridge), which encodes DNA
      homologous to the digested viral termini, the three DNA molecules are able to
      undergo homologous recombination and produce infectious BoHV-1. During the
      recombination process foreign DNA within the DNA bridge is incorporated into the
      BoHV-1 genome, producing rBoHV. In the absence of the DNA bridge virus
      reconstitution does not occur thus eliminating contamination by the
      nonrecombinant parent virus. As REMR used an NsiI site occurring naturally in the
      BoHV-1 genome it can be used for the insertion of foreign DNA into the genome
      without any prior modifications. REMR could also be applied to any herpesvirus
      for which the genome sequence is known.

PMID- 12505644
TI  - Neuronal cell migration for the developmental formation of the mammalian
      striatum.
AB  - The mammalian striatum is the largest receptive component of the basal ganglia
      circuit. It is involved in the control of various aspects of motor, cognitive,
      and emotional functions. In the telencephalon, the striatum has a unique
      histological property totally different from the cortical area and its
      ontogenesis remains largely unknown. In this review, we introduce recent advances
      in the understanding of neuronal cell migration, one of the most critical
      processes in the early phase of histogenesis that occurs in the embryonic
      striatum. It appears that there are three major modes of neuronal cell migration
      in the developmental formation of the striatum. They are (radial) outward,
      tangential, and inward migration, supplying the striatum with projection neurons,
      interneurons, and early-generated transient neurons that originate in the
      preplate, respectively. We challenge the classical concept that the striatum is
      solely derived from the restricted germinal area located in the basal
      telencephalon by providing evidence that striatal development requires the
      intermixture of different types of neurons originating from distinct regions of
      the telencephalon.

PMID- 12505645
TI  - The nucleus isthmi and dual modulation of the receptive field of tectal neurons
      in non-mammals.
AB  - The nucleus isthmi in the dorsolateral tegmentum had been one of the most obscure
      structures in the nonmammalian midbrain for eight decades. Recent studies have
      shown that this nucleus and its mammalian homologue, the parabigeminal nucleus,
      are all visual centers, which receive information from the ipsilateral tectum and
      project back either ipsilaterally or bilaterally depending on species, but not an
      auditory center as suggested before. On the other hand, the isthmotectal pathways
      exert dual, both excitatory and inhibitory, actions on tectal cells in amphibians
      and reptiles. In birds, the magnocellular and parvocellular subdivisions of this
      nucleus produce excitatory and inhibitory effects on tectal cells, respectively.
      The excitatory pathway is mediated by glutamatergic synapses with AMPA and NMDA
      receptors and/or cholinergic synapses with muscarinic receptors, whereas the
      inhibitory pathway is mediated by GABAergic synapses via GABA(A) receptors.
      Further studies have shown that the magnocellular and parvocellular subdivisions
      can differentially modulate the excitatory and inhibitory regions of the
      receptive field of tectal neurons, respectively. Both the positive and the
      negative feedback pathways may work together in a winner-take-all manner, so that
      the animal could attend to only one of several competing visual targets
      simultaneously present in the visual field. Some behavioral tests seem to be
      consistent with this hypothesis. The present review indicates that the tecto
      isthmic system in birds is an excellent model for further studying tectal
      modulation and possibly winner-take-all mechanisms.

PMID- 12505646
TI  - Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents.
      Non-psychoactive cannabinoids, 'entourage' compounds and inhibitors of N-acyl
      ethanolamine breakdown as therapeutic strategies to avoid pyschotropic effects.
AB  - There is good evidence that plant-derived and synthetic cannabinoids possess
      neuroprotective properties. These compounds, as a result of effects upon CB(1)
      cannabinoid receptors, reduce the release of glutamate, and in addition reduce
      the influx of calcium following NMDA receptor activation. The major obstacle to
      the therapeutic utilization of such compounds are their psychotropic effects,
      which are also brought about by actions on CB(1) receptors. However, synthesis of
      the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, which also
      have neuroprotective properties, are increased under conditions of severe
      inflammation and ischemia, raising the possibility that compounds that prevent
      their metabolism may be of therapeutic utility without having the drawback of
      producing psychotropic effects. In this review, the evidence indicating
      neuroprotective actions of plant-derived, synthetic and endogenous cannabinoids
      is presented. In addition, the pharmacological properties of endogenous
      anandamide-related compounds that are not active upon cannabinoid receptors, but
      which are also produced during conditions of severe inflammation and ischemia and
      may contribute to a neuroprotective action are reviewed.

PMID- 12505647
TI  - Zinc takes the center stage: its paradoxical role in Alzheimer's disease.
AB  - There is compelling evidence that the etiology of Alzheimer's disease (AD)
      involves characteristic amyloid-beta (Abeta) deposition, oxidative stress, and
      anomalous metal-Abeta protein interaction. New studies have implicated redox
      active metals such as copper, iron, and zinc as key mediating factors in the
      pathophysiology of Alzheimer's disease. There is also evidence that drugs with
      metal chelating properties could produce a significant reversal of amyloid-beta
      plaque deposition in vitro and in vivo. This paper reviews current observations
      on the etiologic role of zinc in AD. We also discuss the interactions of zinc and
      copper with Abeta, a factor that purportedly facilitates disease processes.
      Finally, we review the protective role of zinc against Abeta cytotoxicity and
      hypothesize how the apparent effect of zinc on AD pathology may be paradoxical,
      The Zinc Paradox. Indeed, complex pathologic stressors inherent to the
      Alzheimer's diseased brain dictate whether or not zinc will be neuroprotective or
      neurodegenerative. Further research on the zinc paradox in AD is needed in order
      to elucidate the exact role zinc plays in AD pathogenesis.

PMID- 12505648
TI  - Synchronous gamma activity: a review and contribution to an integrative
      neuroscience model of schizophrenia.
AB  - Synchronous high frequency (Gamma band) activity has been proposed as a candidate
      mechanism for the integration or 'binding' of distributed brain activities. Since
      the first descriptions of schizophrenia, attempts to characterize this disorder
      have focused on disturbances in such integrative processing. Here, we review both
      micro- and macroscopic neuroscience research into Gamma synchrony, and its
      application to understanding schizophrenia. The review encompasses evidence from
      both animal and human studies for the functional significance of Gamma activity,
      the association between Gamma dysfunction and information processing
      disturbances, and the relevance of specific Gamma dysfunctions to the integration
      and extension of previous disconnection models of schizophrenia. Attention is
      given to the relationship between Gamma activity and the heterogeneous symptoms
      of schizophrenia. Existing studies show that measures of Gamma activity have the
      potential to explain far more of the variance in schizophrenia performance than
      previous neurophysiological measures. It is concluded that measures of Gamma
      synchrony offer a valuable window into the core integrative disturbance in
      schizophrenia cognition.

PMID- 12505649
TI  - Manganese action in brain function.
AB  - Manganese, an essential trace metal, is supplied to the brain via both the blood
      brain and the blood-cerebrospinal fluid barriers. There are some mechanisms in
      this process and transferrin may be involved in manganese transport into the
      brain. A large portion of manganese is bound to manganese metalloproteins,
      especially glutamine synthetase in astrocytes. A portion of manganese probably
      exists in the synaptic vesicles in glutamatergic neurons and the manganese is
      dynamically coupled to the electrophysiological activity of the neurons.
      Manganese released into the synaptic cleft may influence synaptic
      neurotransmission. Dietary manganese deficiency, which may enhance susceptibility
      to epileptic functions, appears to affect manganese homeostasis in the brain,
      probably followed by alteration of neural activity. On the other hand, manganese
      also acts as a toxicant to the brain because this metal has prooxidant activity.
      Abnormal concentrations of manganese in the brain, especially in the basal
      ganglia, are associated with neurological disorders similar to Parkinson's
      disease. Understanding the movement and action of manganese in synapses may be
      important to clarify the function and toxicity of manganese in the brain.

PMID- 12505650
TI  - The human amygdala and the emotional evaluation of sensory stimuli.
AB  - A wealth of animal data implicates the amygdala in aspects of emotional
      processing. In recent years, functional neuroimaging and neuropsychological
      studies have begun to refine our understanding of the functions of the amygdala
      in humans. This literature offers insights into the types of stimuli that engage
      the amygdala and the functional consequences that result from this engagement.
      Specific conclusions and hypotheses include: (1) the amygdala activates during
      exposure to aversive stimuli from multiple sensory modalities; (2) the amygdala
      responds to positively valenced stimuli, but these responses are less consistent
      than those induced by aversive stimuli; (3) amygdala responses are modulated by
      the arousal level, hedonic strength or current motivational value of stimuli; (4)
      amygdala responses are subject to rapid habituation; (5) the temporal
      characteristics of amygdala responses vary across stimulus categories and subject
      populations; (6) emotionally valenced stimuli need not reach conscious awareness
      to engage amygdala processing; (7) conscious hedonic appraisals do not require
      amygdala activation; (8) activation of the amygdala is associated with modulation
      of motor readiness, autonomic functions, and cognitive processes including
      attention and memory; (9) amygdala activations do not conform to traditional
      models of the lateralization of emotion; and (10) the extent and laterality of
      amygdala activations are related to factors including psychiatric status, gender
      and personality. The strengths and weakness of these hypotheses and conclusions
      are discussed with reference to the animal literature.

PMID- 12505651
TI  - Distribution of the AMPA2 glutamate receptor subunit in adult cat visual cortex.
AB  - In this study, we revealed the distribution of the AMPA2 glutamate receptor
      subunit (AMPA2) in the visual cortical areas 17 and 18 of the adult cat by means
      of different techniques. In situ hybridization, with a cat-specific radioactively
      labeled oligonucleotide probe, showed that AMPA2 mRNA was expressed mainly in
      cortical layers II/III and V/VI with a lower expression in layer IV and
      practically no signal in layer I. Immunocytochemistry, using a polyclonal AMPA2
      subunit-specific antibody, showed immunoreactivity almost exclusively in the
      somata and dendrites of pyramidal neurons in cortical layers II/III and V/VI.
      Only a very faint signal was detected in layer IV. Neurons with little or no
      AMPA2 have AMPA receptors that are highly permeable to calcium. By determining
      the location of AMPA2, this study therefore provides a clear examination of the
      distribution of Ca(2+)-impermeable AMPA receptors over the supra- and
      infragranular layers of cat visual cortex. The functional implication of the
      absence of AMPA2 in cortical layer IV and thus the presence of Ca(2+)-permeable
      AMPA receptors in this layer, is still speculative and has yet to be elucidated.

PMID- 12505652
TI  - Selective neurodegeneration of hippocampus and entorhinal cortex correlates with
      spatial learning impairments in rats with bilateral ibotenate lesions of ventral
      subiculum.
AB  - Rats with bilateral ibotenic acid lesions of ventral subiculum were tested in an
      eight-arm radial maze task for spatial learning and memory functions. The
      performance of the lesioned rats was severely impaired relative to control rats
      in both acquisition and retention of the spatial task. Following subicular
      lesions, profound neurodegeneration of the CA1 and CA3 sub sectors of hippocampus
      and entorhinocortical layers I, II, III, V and VI was observed. These results
      support the concept that neurons in the ventral subiculum are a part of the
      neural network along with the above neurons, which could be involved in the
      processing of spatial information.

PMID- 12505653
TI  - Involvement of I(1)-imidazoline receptors in baroreceptor reflex in the caudal
      ventrolateral medulla of rats.
AB  - There is ample evidence to show the existence of center I(1)-imidazoline
      receptors that are involved in the regulation of cardiovascular activities. The
      purpose of this study was to examine the possible role of I(1)-imidazoline
      receptors and alpha(2)-adrenoceptors within the caudal ventrolateral medulla
      (CVLM) in mediating the baroreceptor reflex in anesthetized rats. Unilateral
      microinjection of idazoxan (2 nmol in 50 nl), a mixed antagonist of I(1)
      imidazoline receptors and alpha(2)-adrenoceptors, into the CVLM significantly
      (P<0.01) decreased blood pressure (BP), heart rate (HR), and the firing rate of
      presympathetic neurons in the rostral ventrolateral medulla (RVLM) by 21+/-6
      mmHg, 25+/-5 beats per min and 3.5+/-0.9 spikes/s, respectively. Moreover,
      unilateral injection of idazoxan into the CVLM significantly (P<0.01) reduced the
      inhibitory responses of the ipsilateral RVLM presympathetic neurons evoked by
      stimulation of aortic nerve and elevation of BP, and partially inhibited the
      neuronal cardiac cycle-related rhythm. Depressor responses evoked by aortic nerve
      stimulation were significantly (P<0.01) attenuated 10 and 20 min after bilateral
      microinjection of idazoxan (2 nmol in 50 nl for each side) into the CVLM (-20+/-4
      and -30+/-4 vs. -40+/-1 mmHg). However, injection of yohimbine (500 pmol in 50
      nl), a selective alpha(2)-adrenoceptor antagonist, into the CVLM did not affect
      the resting cardiovascular activities and baroreceptor reflex. It is concluded
      that the CVLM I(1)-imidazoline receptors are involved in maintenance of tonic
      cardiovascular activities and transmission of the baroreceptor reflex.

PMID- 12505654
TI  - Fe2+ decreases the taurine-induced Cl- current in acutely dissociated rat
      hippocampal neurons.
AB  - The effects of ferrous ions (Fe(2+)) on taurine-induced Cl(-) current (I(tau))
      recorded from single neurons, which was freshly isolated from the rat hippocampal
      CA1 area, were studied with conventional whole-cell recording under voltage-clamp
      conditions. Using standard pharmacological approaches, we found that the currents
      gated by concentrations of taurine (<or=10 mM), which existed in about 90% of the
      hippocampal neurons tested, were predominantly mediated by strychnine-sensitive
      glycine receptors. When co-applied with taurine, Fe(2+) effectively depressed
      I(tau) in a concentration-dependent manner, with an IC(50) of 3.76 mM and Hill
      coefficient of 1.01, while preincubation with 1 mM Fe(2+) alone did not affect
      the following membrane currents elicited by taurine. The result suggests that
      resting taurine-gated channels are insensitive to Fe(2+). Since internal cell
      dialysis with 3 mM Fe(2+) failed to modify I(tau), it was deduced that the site
      of action of Fe(2+) is extracellular. Furthermore, the Lineweaver-Burke double
      reciprocal plot of normalized response to taurine against the concentration of
      taurine illustrated that the depression of I(tau) was noncompetitive, therefore
      Fe(2+) may act on the glycine receptor-chloride ionophore complex at a site
      distinct from where taurine binds. Various concentrations of Fe(2+) ranging from
      0.1 to 20 mM depressed I(tau) and this extracellular depression was independent
      of membrane voltage. These results indicate that Fe(2+) decreases I(tau) in
      acutely dissociated rat hippocampal neurons and the inhibition of glycine
      receptors by Fe(2+) might be one possible approach through which Fe(2+) induces
      seizures.

PMID- 12505655
TI  - Molecular volume determines the activity of the halogenated alkane bromoform at
      wild-type and mutant GABA(A) receptors.
AB  - The GABA(A) receptor is an important target for a variety of general anesthetics,
      including halogenated ethers such as isoflurane and halogenated ethers such as
      chloroform. Bromoform is a halogenated alkane that exhibits anesthetic properties
      and has been shown by X-ray crystallography to bind to model anesthetic targets.
      In this study we report the ability of bromoform to potentiate GABA-induced
      current in recombinant GABA(A) receptors composed of alpha(1)beta(2)gamma(2s)
      subunits. Recent studies have shown that specific point mutations in the
      transmembrane (TM) region of the GABA(A) receptor alpha-subunit can selectively
      abolish the modulatory activity of specific general anesthetics, and that
      molecular volume is a key determinant of anesthetic activity. The action of
      bromoform was examined in a series of mutant receptors and compared with the
      activity profiles of three other volatile anesthetics. The pharmacological
      profile of bromoform at the mutant receptors used in this study was similar to
      that seen with halothane, and distinct from that observed for isoflurane and
      chloroform. The molecular volume of bromoform is closest to that of halothane,
      and therefore our data are consistent with the idea that molecular volume is an
      important determinant of inhaled anesthetic activity at the GABA(A) receptor.

PMID- 12505656
TI  - Effects of maternal separation on behavioural sensitization produced by repeated
      cocaine administration in adulthood.
AB  - We examined whether early maternal separation influenced the susceptibility to
      behavioural sensitization produced by repeated intravenous (i.v.) injections of
      cocaine in adult female rats. For the first 21 days of life litters were
      separated from their mother for either 15 min (MS-15) or 180 min/day (MS-180).
      Control animals were subjected only to regular cage changes (animal facility
      reared; AFR). In adulthood, these three groups did not differ in their locomotor
      response to placement in a novel environment or to an acute i.v. injection of
      cocaine. After six additional daily injections of either saline or cocaine and
      following a 7-day drug-free interval, sensitization was assessed by giving all
      rats a challenge i.v. injection of cocaine. Rats exposed to either period of
      maternal separation (MS-15 or MS-180) showed significantly less robust
      sensitization than AFR rats. Therefore, early maternal separation decreased
      susceptibility to behavioural sensitization produced by cocaine in adulthood and
      the specific duration of maternal separation had no effect on this outcome.

PMID- 12505657
TI  - Localization of orexins and their receptors in the rat olfactory system: possible
      modulation of olfactory perception by a neuropeptide synthetized centrally or
      locally.
AB  - Orexin-A and -B, also known as hypocretins, are two neuropeptides acting on
      feeding and sleep. They are specific ligands for two different receptors
      belonging to the G-protein coupled receptors family. Orexin fibers and orexin
      receptor neurons have been previously described in the forebrain olfactory
      system. Using immunocytochemistry, we showed that both orexin-A and -B as well as
      their receptors were present at different levels of the olfactory system, from
      the nasal mucosa to nuclei of the amygdala. A punctuated staining for orexins and
      their receptors was detected at the apical part of the olfactory epithelium; in
      the lamina propria of the mucosa, the staining was localized around olfactory
      nerves. At the ultrastructural level, olfactory neurons and supporting cells were
      found immunoreactive for orexins and their receptors. The labeling was localized
      in dendritic knobs and cilia of neurons, in the apical part and microvilli of
      supporting cells. The finding of immunolabeled cisternae of reticulum strongly
      suggests a local synthesis of both peptides and receptors, confirmed by RT-PCR
      experiments. In forebrain and amygdala regions, we detected numerous orexin
      fibers. Orexin receptors were present in mitral-tufted cells of the bulb and in
      many neuronal perikarya in the anterior olfactory nuclei, piriform cortex and
      amygdala nuclei. Altogether, these results show that orexins and their receptors
      are present at all levels of the olfactory system, from cilia where odors bind to
      their receptors to central regions where integration of olfactory signals occurs.
      They suggest a possible modulation of olfactory perception by these
      neuropeptides.

PMID- 12505658
TI  - Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its
      biochemical characteristics and implication in ischemic neuronal injury.
AB  - The objective of the present study was to determine the biochemical
      characteristics of Ca(2+)-induced mitochondrial swelling (mitochondrial
      permeability transition; mPT) and cytochrome c release in the brain, and to
      clarify its role in neuronal injury following transient forebrain ischemia.
      Mitochondria were isolated from rat brain and liver. Changes in mitochondrial
      volume were measured via light absorbance at 540 nm. Using Western blot analysis,
      we examined the in vitro release of mitochondrial cytochrome c under these
      conditions. Transient forebrain ischemia was induced by 5 min occlusion of the
      common carotid arteries in the gerbil. Cyclosporin A (CsA), a specific mPT
      blocker, and/or trifluoperazine, a blocker of phospholipase A(2), were given
      before and 24 h after ischemia. The number of surviving neurons in the
      hippocampal CA1 sector was counted 7 days after ischemia. Calcium induced a
      moderate decrease of light absorbance in brain mitochondria, which was inhibited
      by CsA. However, calcium induced a much larger decrease of light absorbance in
      liver mitochondria. Calcium induced a moderate release of cytochrome c from brain
      mitochondria, which was not inhibited by CsA. However, calcium induced the
      release of a larger amount of cytochrome c from liver mitochondria. Selective
      neuronal injury due to transient forebrain ischemia was significantly ameliorated
      by treatment with high-dose CsA. The biochemical properties of Ca(2+)-induced
      mitochondrial swelling in the brain are different from those in the liver.
      Cytochrome c is released from brain mitochondria through an mPT-independent
      mechanism. CsA potentially ameliorates delayed neuronal injury in the hippocampus
      due to transient forebrain ischemia.

PMID- 12505659
TI  - Porcine pancreatic group IB secretory phospholipase A2 potentiates Ca2+ influx
      through L-type voltage-sensitive Ca2+ channels.
AB  - Secretory phospholipase A(2) (sPLA(2)) exhibits neurotoxicity in the central
      nervous system. There are high-affinity binding sites of the porcine pancreatic
      group IB sPLA(2) (sPLA(2)-IB) in the brain. sPLA(2)-IB causes neuronal cell death
      via apoptosis in the rat cerebral cortex. Although apoptosis is triggered by an
      influx of Ca(2+) into neurons, it has not yet been ascertained whether the Ca(2+)
      influx is associated with the neurotoxicity of sPLA(2)-IB. We thus examined the
      possible involvement of Ca(2+) in the neurotoxicity of sPLA(2)-IB in the primary
      culture of rat cortical neurons. sPLA(2)-IB induced neuronal cell death in a
      concentration- and time-dependent manner. This death was accompanied by condensed
      chromatin and fragmented DNA, exhibiting apoptotic features. Before apoptosis,
      sPLA(2)-IB markedly enhanced the influx of Ca(2+) into neurons. A calcium
      chelator suppressed neurons from sPLA(2)-IB-induced neuronal cell death in a
      concentration-dependent manner. An L-type voltage-sensitive Ca(2+) channel (L
      VSCC) blocker significantly protected the sPLA(2)-IB-potentiated influx of
      Ca(2+). On the other hand, blockers of N-VSCC and P/Q-VSCC did not. An L-VSCC
      blocker protected neurons from sPLA(2)-IB-induced neuronal cell death. In
      addition, the L-VSCC blocker ameliorated the apoptotic features of sPLA(2)-IB
      treated neurons. Neither an N-VSCC blocker nor P/Q-VSCC blockers affected the
      neurotoxicity of the enzyme. In conclusion, these findings demonstrate that the
      influx of Ca(2+) into neurons play an important role in the neurotoxicity of
      sPLA(2)-IB. Furthermore, the present study suggests that L-VSCC contribute to the
      sPLA(2)-IB-potentiated influx of Ca(2+) into neurons.

PMID- 12505660
TI  - Mesencephalic trigeminal neurons are innervated by nitric oxide synthase
      containing fibers and respond to nitric oxide.
AB  - In the present study we found that mesencephalic trigeminal (Mes-V) neurons of
      the rat are innervated by nitrergic fibers and that nitric oxide (NO) modifies
      the electrophysiological properties of these cells. Mes-V neurons were surrounded
      by a network of fibers that contained neuronal nitric oxide synthase (nNOS);
      these fibers gave rise to terminal-, bouton-like structures which ended in Mes-V
      cells bodies. These cells, which did not display nNOS-like immunoreactivity were
      immunoreactive to a cGMP antibody. By performing intracellular recordings in the
      adult rat brain slice preparation, the effects of diethylenetriamine/NO adduct
      (DETA/NO) applications were examined. DETA/NO induced a depolarization that
      averaged 2.2 mV (range: 1-6 mV) in nine of 22 neurons. In 15 of 22 neurons (68%
      of the cells), there was a decrease in current threshold from 0.74 to 0.60 nA
      (19%; P<0.001). The excitatory effects of DETA/NO were abolished by ODQ, a
      blocker of soluble guanylate cyclase. Input resistance (R(in)) decreased in 80%
      of the cells from a mean of 24.8 to 20.6 Momega (17%; P<0.001) and the membrane
      time constant (tau(m)) decreased from 7.5 to 5.6 ms (25%; P<0.05). The 'sag' seen
      in the membrane response of these cells to current pulses was augmented during
      DETA/NO application. These findings indicate that there is a nitrergic
      innervation of Mes-V neurons and that these sensory cells are target for NO that
      may act on them as an excitatory neuromodulator promoting the synthesis of
      intracellular cGMP.

PMID- 12505661
TI  - Fructose-1,6-bisphosphate preserves intracellular glutathione and protects
      cortical neurons against oxidative stress.
AB  - Fructose-1,6-bisphosphate (FBP), an endogenous intermediate of glycolysis,
      protects the brain against ischemia-reperfusion injury. The mechanisms of FBP
      protection after cerebral ischemia are not well understood. The current study was
      undertaken to determine whether FBP protects primary neurons against hypoxia and
      oxidative stress by preserving reduced glutathione (GSH). Cultures of pure
      cortical neurons were subjected to oxygen deprivation, a donor of nitric oxide
      and superoxide radicals (3-morpholinosydnonimine), an inhibitor of glutathione
      synthesis (L-buthionine-sulfoximine) or glutathione reductase (1,3-bis(2
      chloroethyl)-1-nitrosourea) in the presence or absence of FBP (3.5 mM). Neuronal
      viability was determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium bromide assay. FBP protected neurons against hypoxia-reoxygenation
      and oxidative stress under conditions of compromised GSH metabolism. The efficacy
      of FBP depended on duration of hypoxia and was associated with higher
      intracellular GSH concentration, an effect partly mediated via increased
      glutathione reductase activity.

PMID- 12505662
TI  - Powerful cyclosporin inhibition of calcium-induced permeability transition in
      brain mitochondria.
AB  - The mitochondrial permeability transition (mPT) is considered to be an important
      mediator of apoptosis and necrosis, and is specifically blocked by cyclosporin A
      (CsA). CsA has been shown to exert a potent neuroprotective action in vivo when
      allowed to cross the blood-brain barrier in various animal models of acute
      neurological insults and neurodegenerative disease. The neuroprotective effect of
      CsA is considered to be mediated through specific inhibition of the mitochondrial
      permeability transition pore (mPTP) and through inhibition of neuronal
      calcineurin activity. Characterization of mPT has mainly been performed in liver
      and heart mitochondria, and some brain studies have reported a decreased
      inhibitory effect of CsA and questioned the importance of mPT in brain-derived
      mitochondria. We have used the de-energized model of swelling to examine the mPT
      in brain-derived non-synaptosomal mitochondria. Ca(2+)-induced swelling was
      evaluated by electron microscopy and by measurement of spectrophotometric
      alterations in light scattering. Permeability transition was readily induced in a
      majority of the mitochondria at a wide range of Ca(2+) levels and was powerfully
      inhibited by CsA with a half-maximal effect at approximately 23 nM CsA. The
      swelling kinetics and CsA effects were comparable to previous findings in de
      energized liver and heart mitochondria. Careful characterization of mPT and CsA
      effects in brain-derived mitochondria is the first step in evaluating newly
      developed CsA analogues capable of crossing the blood-brain barrier and
      preferentially entering the brain. The importance of CsA causing a shift of the
      mitochondrial sensitivity to Ca(2+) in neurological disorders is discussed.

PMID- 12505663
TI  - The role of the melanocortin system and the melanocortin-4 receptor in ring dove
      (Streptopelia risoria) feeding behavior.
AB  - The melanocortin-4 receptor (MC4-R) is an important mediator of the effects of
      two melanocortin system ligands, alpha melanocyte stimulating hormone (alpha-MSH)
      and agouti-related peptide (AGRP), on feeding behavior and energy balance in
      mammals. Although an avian homologue of the mammalian MC4-R has recently been
      identified, there is little information on the role of this receptor and the
      melanocortin system in avian feeding and body weight regulation. In these
      studies, we measured changes in feeding behavior in ring doves (Streptopelia
      risoria) following intracerebroventricular (i.c.v.) injection of various
      melanocortin receptor agonists and antagonists. The selective MC4-R antagonist
      HS014 elevated food intake within 4 h at all three doses tested (0.02, 0.2, and 2
      nmol). A 1 nmol dose of the endogenous antagonist AGRP also stimulated feeding
      but only after a post-injection interval of 10 h. Surprisingly, the MC3-R and MC4
      R antagonist SHU9119 not only failed to stimulate food intake at the same doses
      as HS014, but actually inhibited food intake at 8 h after injection. Whether this
      was due to toxicity effects or differences in the pharmacology of avian and
      mammalian melanocortin receptors remains to be determined. Food-deprived doves
      showed a fourfold increase in the number of AGRP-immunoreactive cells in the
      tuberal region of the hypothalamus and 5 ng of the MC3-R and MC4-R agonist MTII
      significantly attenuated the amount of food consumed by food-deprived birds that
      were allowed to re-feed. These data support a role for the melanocortin system
      and the melanocortin-4 receptor in the ring dove feeding behavior.

PMID- 12505664
TI  - Area postrema mediates gastric motor response induced by apomorphine in rats.
AB  - The effects of apomorphine administration on the autonomic responses were
      investigated in rats. Distinctive gastric motor responses were observed after the
      intravenous administration of apomorphine (0.1 mg/kg body weight). Gastric motor
      responses in the distal stomach induced by apomorphine administration were
      classified into two types. One type involved inhibition of phasic contractions
      which appeared just after the administration of apomorphine. The other involved
      an increase in the frequency of small phasic contractions accompanied by
      increased gastric tone appearing with a relatively longer delay. No relaxation
      was observed in either the proximal or distal stomach. These gastric motor
      responses showed a dose-response effect to the amount of apomorphine administered
      (0.002-0.1 mg/kg body weight). In addition, submandibular salivary secretion was
      observed in response to the intravenous administration of apomorphine at a dose
      of 3 or 10 mg/kg body weight. Pretreatment with domperidone (1 or 2 mg/kg body
      weight) or the ablation of the area postrema (AP) abolished the gastric motor
      response and salivary secretion induced by the administration of apomorphine. In
      conclusion, rats showed definitive autonomic phenomena in response to the
      administration of apomorphine. Dopamine 2-like receptors situated in the AP
      mediate apomorphine-induced autonomic phenomena in rats.

PMID- 12505665
TI  - Distribution of the voltage gated sodium channel Na(v)1.3-like immunoreactivity
      in the adult rat central nervous system.
AB  - Voltage-gated sodium channels are transmembrane proteins responsible for the
      initiation and propagation of action potentials. One subtype, Na(v)1.3 (brain
      type III) is tetrodotoxin sensitive and fast inactivated. Na(v)1.3 has been shown
      to be expressed at low levels in the adult rat, but to be upregulated after
      sciatic nerve axotomy in the dorsal root ganglia. In the present study, we used
      immunohistochemistry to look at the distribution of Na(v)1.3 in the adult rat
      central nervous system. We used a polyclonal antibody, raised against residues
      511-524. This epitope corresponds to the sequence located in the intracellular
      loop between domains I and II of Na(v)1.3 and is specific for this sodium channel
      subtype. We found Na(v)1.3-like immunoreactivity (-LI) neurons in the cerebral
      cortex, hippocampal formation, colliculi, and mesencephalic reticular formation.
      Na(v)1.3-LI was observed in fiber tracts such as the corpus callosum, anterior
      commissure, corticofugal fibers, lateral lemniscus, and cerebellar peduncles.
      Na(v)1.3-LI was particularly intense in sensory nerve tracts such as the
      mesencephalic trigeminal tract, vestibulospinal tract, or spinal trigeminal
      tract. In the spinal cord, Na(v)1.3-LI was intense throughout the white matter
      and the dorsal roots. In the spinal cord grey matter, Na(v)1.3-LI fibers
      terminate in the deep laminae of the dorsal horn and in the ventral horn.
      Na(v)1.3-LI was also found in motoneurons as well as in ventral roots. This study
      shows that Na(v)1.3 is present at the protein level in the adult rat.

PMID- 12505666
TI  - Electrophysiology of optic nerve input to suprachiasmatic nucleus neurons in rats
      and degus.
AB  - Neurons in the mammalian suprachiasmatic nucleus (SCN), the principal pacemaker
      of the circadian system, receive direct retinal input. Some SCN neurons respond
      to retinal illumination or optic nerve stimulation with changes in firing rates.
      In nocturnal rodents, retinal illumination increases firing rates of a large
      majority and decreases firing rates of a minority of responsive neurons. In two
      species of diurnal rodent, these proportions are altered or even reversed. Since
      retinal input to the SCN has been reported to involve release of the excitatory
      neurotransmitter glutamate, the mechanism mediating suppressions is unknown. We
      studied responses of neurons in SCN slices from diurnal degus and nocturnal rats
      to optic nerve stimulation. To test whether suppressions are mediated indirectly
      by release of the inhibitory neurotransmitter GABA from SCN neurons that are
      first activated by glutamate release, we attempted to block suppressions by
      adding to the bath either APV, an antagonist for excitatory glutamate receptors,
      or bicuculline, a GABA(A) receptor antagonist. If glutamate is the only
      neurotransmitter released by optic nerves in the SCN, APV should prevent both
      activations and suppressions in response to optic nerve stimulation. We found
      that APV had little effect on suppressions although it effectively blocked
      activations. Bicuculline blocked most suppressions. These findings are
      inconsistent with a model in which the retina provides only excitatory glutamate
      input to the SCN via NMDA receptors. Since some retinal fibers in adult mammals
      contain GABA, it is possible that the retinal innervation of the SCN includes
      both glutamate- and GABA-containing axons.

PMID- 12505667
TI  - The role of cytokines and adhesion molecules in axon degeneration after
      peripheral nerve axotomy: a study in different knockout mice.
AB  - The loss of axons and axonal dysfunction has become of outstanding interest with
      respect to degenerative and inflammatory diseases of the central and peripheral
      nervous system. In particular in terms of demyelinating diseases such as multiple
      sclerosis it is important to know the mechanisms which are responsible for the
      degeneration and destruction of axons. Here we focused on the loss or
      preservation of axons after induction of Wallerian degeneration in transected
      mouse sciatic nerves. We examined the distal transected nerve segments of
      different knockout mice (ICAM-1; TNF-alpha; iNOS; IL-6) 6 days after axotomy.
      Despite a distinct number of invading macrophages which phagocytosed most of the
      myelin and axonal debris, we were able to demonstrate, that animals which are
      deficient for the cell adhesion molecule ICAM-1 and the cytokine TNF-alpha showed
      a significantly higher number of preserved axons within the degenerating distal
      nerve stump. Since macrophage invasion is known to be impaired in the absence of
      ICAM-1, these data indicate an essential role of these cells and their secreted
      factors, namely TNF-alpha, but not nitric oxide or IL-6 in the destruction of the
      axonal cytoskeleton in the peripheral nervous system.

PMID- 12505668
TI  - Identification of temperature-sensitive neural circuits in mice using c-Fos
      expression mapping.
AB  - Expression of the inducible transcription factor c-Fos was mapped in mouse brain
      to identify neural circuits selectively involved in response to cold and hot
      external temperatures. Male C57BL/6J mice were exposed acutely or repeatedly
      (seven sessions) to 10 or 34 degrees C in sound-attenuated chambers. Control mice
      were acclimated to exposure to the experimental room at 20 degrees C. All animals
      were sacrificed at 90 min for immunohistochemical analysis. A statistically
      significant induction of c-Fos was observed in the shell of nucleus accumbens and
      posterior medial cortical amygdala only following the acute thermal exposure,
      showing a significant habituation of the response to repeated treatments, a
      finding arguing against specificity of responses in these nuclei to thermal
      exposures. In contrast, expression of c-Fos was significantly increased following
      both acute and repeated thermal exposures in subregions of hypothalamus (the
      median and medial preoptic nuclei, the paraventricular nucleus of hypothalamus
      and the posterior hypothalamic area), septum (the ventral and dorsal portions of
      the lateral septum), midbrain (the periaqueductal gray and the intermediate
      layers of superior colliculus), as well as in the dentate gyrus and the
      paraventricular nucleus of thalamus, suggesting specificity of their responses to
      external temperatures. Expression of c-Fos was also significantly increased in
      the Edinger-Westphal nucleus following acute thermal exposures versus control
      mice, but not versus mice repeatedly exposed to cold and hot temperatures,
      providing modest support for thermal specificity of c-Fos response in this
      nucleus. While thermal sensitivity of hypothalamic structures has been previously
      confirmed by many authors, the present study identifies a number of structures
      previously not found to be responsive to changes in external temperature, and
      lays ground for future work important for identification of neural circuits
      involved in thermoregulation.

PMID- 12505669
TI  - Preoptic area warming inhibits wake-active neurons in the perifornical lateral
      hypothalamus.
AB  - Activation of the preoptic area (POA) warm sensitive neurons is known to promote
      non-REM (NREM) sleep and inhibit neuronal discharge in arousal-related brain
      structures. The perifornical area of the lateral hypothalamus (PF/LH) was
      recently recognized to be an additional important arousal promoting region. We
      studied the behavior of PF/LH neurons in rats during the normal sleep-wake cycle
      and in response to local POA warming. Most PF/LH neurons were wake-active, and
      exhibited low discharge throughout NREM. Seventy four percent of these wake
      active neurons exhibited moderate or strong activation in REM sleep compared to
      NREM sleep. A substantial group (26%) exhibited very low discharge in REM as well
      as NREM sleep. Fifty two percent of units in the PF/LH area were responsive to
      POA warming; 90% of responsive neurons exhibited a significant reduction (
      26.47+/-2.16% for 1 degrees C of POA warming) in their discharge rate. The
      inhibitory effect of POA warming on PF/LH neurons was not associated with EEG
      slowing. This study supports the hypothesis that sleep induction by POA warm
      sensitive neurons is mediated through the inhibition of multiple arousal-related
      structures.

PMID- 12505670
TI  - Mechanical hyperalgesia in rat models of systemic and local hyperglycemia.
AB  - Mechanical hyperalgesia is an early symptom of diabetic neuropathy. To evaluate
      the mechanisms underlying this symptom, it was studied and compared in rat models
      of systemic and local hyperglycemia. Systemic hyperglycemia was induced by a
      single injection of streptozotocin (STZ, 50 mg/kg). Local hyperglycemia either in
      L(5) dorsal root ganglion (DRG) or a segment of the sciatic nerve at mid-thigh
      level was maintained by perfusion with 30-mM glucose solution delivered from a
      surgically implanted osmotic minipump. Mechanical hyperalgesia was assessed using
      modified von Frey filaments and hind limb withdrawal threshold measurements.
      During 2 weeks of STZ-induced diabetes rat systemic blood glucose level increased
      from 5.1+/-0.3 to 23+/-1.9 mM and limb withdrawal threshold decreased by
      approximately 30% bilaterally. During 2 weeks of local perfusion systemic blood
      glucose did not change; however, rats that underwent perfusion of the DRG or
      sciatic nerve with glucose exhibited a rapid (completed in approximately 1 week)
      40-50% decrease in ipsilateral limb withdrawal threshold. Perfusion of the
      sciatic nerve with the normoglycemic buffer solution did not affect withdrawal
      thresholds. The aldose reductase inhibitor sorbinil (2.5 mg/ml) when added to 30
      mM glucose perfusion solution prevented hyperalgesia. These data suggest that
      mechanical hyperalgesia in diabetic animals may, at least in part, result from
      focal injury caused by a direct toxic effect of glucose in the peripheral nervous
      system. These data also support the idea of activation of aldose reductase and
      polyol pathway as an important mechanism of hyperglycemia-induced impairment of
      nerve function.

PMID- 12505671
TI  - Assessment of the seizure susceptibility of Wistar Audiogenic rat to
      electroshock, pentyleneterazole and pilocarpine.
AB  - This work evaluates the seizure susceptibility of nai;ve female Wistar Audiogenic
      rats (WARs), a genetic model of reflex epilepsy in which seizures are induced by
      high-intensity sound stimulation (120 dB SPL), to other pro-convulsive stimuli:
      transauricular electroshock (ES), pentylenetetrazole (PTZ) and pilocarpine
      (PILO). Normal Wistar rats from the main breeding stock of the Institute of
      Biological Sciences, UFMG were taken as controls. Electroshock seizures were
      induced through a pair of ear-clip electrodes (10 mA, at a frequency of 60 Hz,
      applied for 1 s). In order to test WAR susceptibility to chemically induced
      seizures, animals were treated either with PTZ (37.5 mg/kg i.p.) or PILO (200,
      270 and 300 mg/kg i.p.). Seizure severity was evaluated by appropriate behavioral
      severity index scales (SI) specific to each epilepsy model and tested for
      statistical significance using the non-parametric Mann-Whitney Rank Sum test.
      Results show a significantly greater susceptibility of WARs for ES (SI(WAR)=3+/
      3/3, SI(Wistar)=1+/-1/1; median+/-interquartile range 25%/75%, P<0.01) and PTZ
      (SI(WAR)=4+/-4/4, SI(Wistar)=1+/-1/4; median+/-interquartile range 25%/75%,
      P<0.02), as indicated by significantly higher SI scores and shorter latencies for
      seizure onset (T(WAR)=71+/-7 s, T(Wistar)=94+/-8 s; P<0.05 Student t-test, mean+/
      S.E.M.). Although PILO also caused higher SI scores in WARs (WAR(200 mg)=1+/-1/1,
      Wistar(200 mg)=1+/-1/1; WAR(270 mg)=1.5+/-1/2, Wistar(270 mg)=1+/-1/1.25; WAR(300
      mg)=9+/-1/9, Wistar(300 mg)=4+/-1.5/7.5; median+/-interquartile range 25%/75%),
      statistically significant differences were not observed. In conclusion, our
      results show that WARs have an inherited broader predisposition for seizures.

PMID- 12505672
TI  - Long-term interactions between opioid and cannabinoid agonists at the cellular
      level: cross-desensitization and downregulation.
AB  - In the present study we investigated long-term interactions between opioid and
      cannabinoid drugs at several steps along their cellular signal transduction
      pathways. For this purpose we co-transfected HEK-293 and COS-7 cells with delta
      opioid (DOR) and CB1-cannabinoid receptors, and examined the effect of prolonged
      exposure to either opioid (etorphine) or cannabinoid (DALN) agonists on DOR and
      CB-1 receptor density and on the ability of subsequent application of the
      agonists to activate G-proteins (as measured by [35S]GTPgammaS binding) and to
      inhibit cAMP production. In HEK-293 cells, etorphine induced both homologous and
      heterologous desensitization, while DALN induced only homologous desensitization.
      This asymmetric cross-desensitization coincided with asymmetric cross
      downregulation: etorphine downregulated the binding of the cannabinoid ligand
      [3H]CP55,940, while DALN failed to reduce the binding of the opioid ligand
      [3H]diprenorphine. In contrast to the asymmetric desensitization in HEK-293
      cells, COS-7 cells presented a two-way cross-desensitization between opioid and
      cannabinoid agonists, and DALN downregulated the binding of [3H]diprenorphine in
      these cells. Thus, a complete correlation was found between downregulation and
      reduction in cell responsiveness ('desensitization'). Moreover, when opioid
      downregulation in HEK-293 cells was inhibited by either hypertonic sucrose
      solution or protein kinase inhibitors, desensitization was suppressed to the same
      extent. These results suggest that, under the present experimental conditions,
      the reduction in cell responsiveness resulted primarily from downregulation of
      the receptors.

PMID- 12505673
TI  - Corticotropin-releasing factor in the dorsal raphe nucleus regulates activity of
      lateral septal neurons.
AB  - Corticotropin-releasing factor (CRF) has substantial effects on brain
      serotonergic activity, especially in limbic structures related to stress and
      anxiety. For example, relatively low doses of CRF administered into the dorsal
      raphe nucleus (DRN) decrease DRN unit activity and serotonin release in the
      lateral septum (LS), a limbic target of the DRN. In contrast, higher doses of CRF
      tend to be excitatory on both endpoints. The present experiment sought to
      establish the functional connection between CRF effects in the DRN and the
      ultimate effect on activity in the LS as a terminal region. We recorded the
      effects of CRF (3, 10, 30 and 100 ng in 100 nl of artificial cerebrospinal fluid)
      administered into the DRN upon LS unit activity. In general, the lower doses of
      CRF (3 and 10 ng) had a facilitatory effect on LS unit activity, peaking at about
      15-20 min post-injection. The higher doses had a more complex effect with an
      early suppression of unit responding maximizing at about 5 min followed by a
      facilitatory rebound, especially at the 100 ng dose, maximizing at about 20 min.
      Taken with previous studies demonstrating an inhibitory effect of 5-HT on
      neuronal activity in LS, the findings suggest that CRF regulation of the DRN is
      translated to changes in LS activity. This effect may underlie certain coping
      behaviors in response to stress.

PMID- 12505674
TI  - Enhanced thermal antinociceptive potency and anti-allodynic effects of morphine
      following spinal administration of endotoxin.
AB  - Recently, an animal model of central inflammation characterized by widespread
      cutaneous hyperalgesia and allodynia following intracerebroventricular (i.c.v.)
      administration of lipopolysaccharide (LPS) was described. In the present study,
      we demonstrate that central administration of LPS via intrathecal (i.t.)
      injection produces bilateral tactile allodynia and thermal hyperalgesia in the
      rat. Also, the effects of morphine-induced antinociception were determined in
      this model. Here we demonstrate enhanced thermal antinociceptive potency of i.t.
      morphine in LPS-treated rats compared to controls. Intrathecal morphine was also
      effective in alleviating the tactile allodynia induced by LPS. Both the
      antinociceptive and anti-allodynic effects produced by i.t. morphine were
      completely antagonized by pretreatment with subcutaneous naloxone (1 mg x kg(
      1)). This study demonstrates the presence of both heat hyperalgesia and
      mechanical allodynia following central administration of LPS, and an increased
      antinociceptive potency of i.t. morphine in this model.

PMID- 12505675
TI  - Mechanisms of pain-induced local cerebral blood flow changes in the rat sensory
      cortex and thalamus.
AB  - It is a well-known phenomenon that cerebral blood flow is coupled to neural
      activation induced by non-noxious somatosensory stimulation. However, basic
      questions related to pain-induced cerebral blood flow changes remain unanswered.
      In the present study, the sciatic nerve of anesthetized rats was subjected to
      electric stimulation with noxious and non-noxious parameters. Changes in local
      cerebral blood flow and neuronal activity were determined simultaneously in the
      sensory cortex and in the thalamus by laser-Doppler flowmetry and c-fos
      immunohistochemistry, respectively. The role of different vasoregulatory
      mechanisms and the pain-induced increase in mean arterial blood pressure (MABP)
      were examined with specific blocking agents and by means of rapid intra-arterial
      transfusion. Noxious stimulation resulted in significant enhancement of neuronal
      activity both in the thalamus and in the somatosensory cortex indicated by marked
      c-fos expression in these areas. Cortical and thalamic blood flow (cBF and tBF)
      increased by 47+/-4 and 44+/-3% during the stimulation while the MABP elevated by
      35+/-2%. Similar changes in MABP induced by intra-arterial transfusion had no
      effect on tBF, while cBF increased only by 18+/-5%. Blockade of ATP sensitive
      potassium channels (K(+)(ATP)) and sympathetic beta-receptors significantly
      attenuated the pain-induced blood flow increases in both investigated areas,
      while inhibition of nitric oxide synthase was effective only in the thalamus. The
      blockade of the sympathetic alpha-receptors, opiate receptors, and the
      cyclooxygenase enzyme had no effect on the pain-induced cerebral blood flow
      elevations. These findings demonstrate that during noxious stimulation, cerebral
      blood flow is adjusted to the increased neural activity by the interaction of
      vasoconstrictor autoregulatory and specific vasodilator mechanisms, involving the
      activation of sympathetic beta-receptors, K(+)(ATP)-channels and the release of
      nitric oxide.

PMID- 12505676
TI  - Anti-amyloid beta activity of metallothionein-III is different from its neuronal
      growth inhibitory activity: structure-activity studies.
AB  - Recent studies have shown that metallothionein-III (MT-III), but not MT-I or -II,
      antagonizes both the neurotrophic and neurotoxic effects of amyloid beta peptides
      (Abetas). Further, its anti-Abeta-toxicity effect was attributed to the fact that
      it inhibits the formation of fibrillar Abeta. MT-III alone also affects neuron
      survival in culture-promoting at low but inhibiting at high concentrations. To
      characterize these biological activities of MT-III in relation to its neuronal
      growth inhibitory activity discovered by Uchida et al. [Neuron 7 (1991) 337-347],
      we here studied effects of the P7S/P9A double mutant, and the N- and C-terminal
      domains of MT-III on primary cultures of rat embryonic cortical neurons in the
      presence and absence of Abeta. Results show that (i). only the wild-type MT-III
      inhibited the formation of SDS-resistant Abeta aggregates and protected cortical
      neurons from the toxic effect of Abeta, and (ii). both the wild type and the N
      terminal domain of MT-III promote neuron survival at low concentrations but
      inhibited it at high concentrations. On the basis of these findings, we conclude
      that the anti-Abeta activity of MT-III is different from its neuronal growth
      inhibitory activity and suggest that the increased trophic activity of AD brain
      extracts could be attributed to its low MT-III content.

PMID- 12505677
TI  - Simultaneous recordings of wind-up of paired spinal dorsal horn nociceptive
      neuron and nociceptive flexion reflex in rats.
AB  - To study the sensory-motor interaction of spinal processing underlying the
      neuronal mechanisms of the nociceptive flexion reflex (NFR) and its temporal
      facilitation, 16 spinal dorsal horn (DH) wide-dynamic-range (WDR) neurons and
      paired 16 single motor units (SMU) from the gastrocnemius soleus muscle (GS) were
      simultaneously recorded using extracellular single unit and electromyographic
      techniques in spinal, halothane-anesthetized rats. The paired DH WDR neuron and
      GS SMU showed a parallel increase in the firing rate and duration of spike
      responses to noxious pinch stimuli applied to their common cutaneous receptive
      field (cRF) on the ipsilateral hind paw skin. Innocuous brush or pressure evoked
      no, or less, firing in the SMU but evoked a graded increase in spike responses in
      the simultaneously-recorded WDR neuron. Moreover, both pressure and noxious pinch
      stimuli evoked a short-lasting after-discharge (for several min) in the WDR
      neuron but without any after-discharge in the simultaneously-recorded SMU. The
      paired WDR neuron and SMU also showed a parallel basal response (termed as early
      and late components according to latency), after-discharge and wind-up of the
      late response to repetitively applied supra-threshold electrical stimulation
      (intensity: >1.5 T, duration: 1 ms and frequency: 1 Hz for 15 s). Linear
      regression and cross-correlation histogram analyses showed that the DH WDR neuron
      had a significant correlation with the simultaneously-recorded SMU and they were
      functionally located in the spinally-organized NFR circuitry via polysynaptic
      connections. Systemic administration of fentanyl, an opioid receptor agonist,
      resulted in a parallel, naloxone-reversible suppression of both basal late
      response component and wind-up response in both WDR neuron and SMU paired;
      however, fentanyl suppressed only the early response of the SMU without any
      effect on that of the DH WDR neuron. The present results provide new direct
      evidence showing an essential role of spinal DH WDR neurons in the mediation of
      spinally-organized NFR as well as its temporal facilitation (wind-up). Based on
      these data, the spinal DH WDR neuron seems to function as a signal discriminator
      or frequency encoder of multireceptive primary afferent impulses that may
      determine excitable level of motor output and the occurrence of a behavioral NFR
      via polysynaptic connections. Consequently, the spinal WDR neuron-mediated NFR
      and its temporal facilitation are likely to be modulated by spinal endogenous
      opioid peptides via opioid receptors on the nociceptive sensory components of the
      spinally-organized NFR circuitry.

PMID- 12505678
TI  - Adenosine A1 receptors regulate the response of the mouse circadian clock to
      light.
AB  - The purine nucleoside, adenosine, has been implicated in the regulation of
      circadian phase in the hamster. In the current report, we present pharmacological
      evidence supporting the involvement of adenosine A1 receptors in the regulation
      of the response of the circadian clock to light in mice. Systemic injection of
      the selective adenosine A1 receptor agonist, N(6)-cyclohexyladenosine (CHA; 0.3
      mg/kg) resulted in a 49% reduction (P<0.05) in the magnitude of light-induced
      phase delays. The inhibitory effect of CHA on light-induced phase delays was dose
      dependent over a range of 0.1 to 5 mg/kg with an apparent EC(50) of 0.3 mg/kg.
      Prior administration of the selective adenosine A1 receptor antagonist
      dipropylcyclopentylxanthine (DPCPX; 1 mg/kg) completely blocked the effect of CHA
      on photic phase delays. Finally, CHA significantly attenuated light-induced
      phospho-extracellular signal-related kinases (ERK) immunoreactivity in the mouse
      suprachiasmatic nucleus (SCN), consistent with a mode of action involving events
      that occur early in the signaling cascade through which photic information is
      conveyed to the circadian clock. These data indicate that the role of adenosine
      in the regulation of circadian phase is similar in mice and hamsters.

PMID- 12505679
TI  - Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are
      associated with salt appetite in the deoxycorticosterone-treated rat.
AB  - Tachykinins are a family of neuropeptides that inhibit salt appetite. Although
      decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats,
      no decrease is seen in natriorexic sodium-replete rats that are administered the
      aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis
      of tachykinins could not account for increased appetite, we hypothesized that
      increased salt appetite was due to a downregulation of tachykinin receptors.
      Thus, we injected rats with DOCA once daily for 11 days and analyzed tachykinin
      receptor subtype, neurokinin 3 (NK3r)-immunoreactivity by Western blot analysis
      since intracerebroventricular injection of senktide (NK3r agonist) attenuates
      salt intake in DOCA-treated animals. We examined NK3r-immunoreactivity in several
      brain regions thought to be associated with the control of water and electrolyte
      balance including the bed nucleus of the stria terminalis, central nucleus of the
      amygdala, diagonal band of Broca, hippocampus, nucleus tractus solitarius,
      parabrachial nucleus, paraventricular nucleus of the hypothalamus, and supraoptic
      nucleus. Consistent with our hypothesis, we found decreased NK3r-immunoreactivity
      in all brain regions analyzed except for increases in the amygdala and no changes
      in the paraventricular nucleus of the hypothalamus. To examine whether DOCA's
      effects on NK3r synthesis are direct, we used differentiated N1E-115
      neuroblastoma cells that express NK3r and treated them with a range of
      concentrations of DOCA and found a dose-dependent decrease in NK3r-mRNA abundance
      via Northern blotting. The present results suggest that the tachykinin receptors
      are downregulated after subchronic DOCA treatment and this finding is consistent
      with the hypothesis that suppressed inhibition of salt appetite as mediated
      through the tachykininergic system.

PMID- 12505680
TI  - Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients.
AB  - We assessed muscarinic M(1), M(2) and M(4) receptor subtypes in the hippocampus
      of Alzheimer's and control brains by receptor autoradiography using ligands such
      as [(125)I]muscarinic toxin-1 ([(125)I]MT-1, M(1) selective), [(3)H]AFDX-384
      (M(2) partially selective) and [(125)I]muscarinic toxin 4 ([(125)I]M(4) toxin-1,
      M(4) selective). Our results revealed a significant decrease in muscarinic M(4)
      receptor binding in the dentate gyrus and CA4 regions of brain sections from
      Alzheimer's patients compared to controls. No changes in the density of M(1) or
      M(2) receptor binding were observed. Our findings suggest that, relative to other
      muscarinic receptor subtypes, the M(4) receptor could be the subtype which is
      selectively compromised in Alzeheimer's disease (AD).

PMID- 12505681
TI  - mGlu5 receptor antagonist decreases Fos expression in spinal neurons after
      noxious visceral stimulation.
AB  - In this study we examined the effects of the glutamate metabotropic subtype 5
      (mGlu5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on Fos
      expression in the spinal cord in a model of visceral pain in the rat. We show
      that noxious stimulation increases the number of Fos-positive neurons in the
      dorsal horn of the thoracic and lumbar spinal cord, and that pretreatment with
      MPEP significantly reduces the number of Fos-positive neurons in these areas.
      These data indicate that mGlu5 is involved in the transmission of visceral pain
      in the spinal cord.

PMID- 12505682
TI  - Ultrastructural study of glutamate- and GABA-immunoreactive terminals contacting
      the primary afferent fibers in frog spinal cord. A double postembedding
      immunocytochemical study.
AB  - The in vitro HRP application to the dorsal root of the frog spinal cord produced
      an intensive staining of primary afferent fibers. A double postembedding GABA and
      glutamate immunocytochemical study revealed GABA- or glutamate-immunopositive
      presynaptic boutons establishing axo-axonic synapses onto HRP-stained primary
      afferent fibers in the spinal cord intermedial zone.

PMID- 12505683
TI  - Delayed effect of administration of COX-2 inhibitor in mice with acute cerebral
      ischemia.
AB  - This study was designed to investigate the time lag of effect of NS398, selective
      COX-2 inhibitor, on infarct volume and neurologic deficits in mice with
      experimentally-induced cerebral ischemia. Our results showed that the beneficial
      effect of NS398 on reduction of infarct volume and improvement of neurologic
      deficits were noted more than 24 h after the injection regardless of the
      administration timing.

PMID- 12505684
TI  - Induction of heat shock protein 40 and GrpE mRNAs following transient focal
      cerebral ischemia in the rat.
AB  - Cerebral ischemia is associated with the induction of several heat shock proteins
      (HSPs), but the effects on HSP40 and GrpE are less clear. The present study
      investigated the induction of Hsp40 and GrpE mRNAs following 30 min of middle
      cerebral artery occlusion in the rat model. Reverse transcription-polymerase
      chain reaction (PCR) and in situ hybridization analyses showed significant
      induction of both mRNAs in the ischemic cortex. These results demonstrate the
      synergic induction of HSP70 molecular chaperone machinery in cerebral ischemia.

PMID- 12505685
TI  - No reduction of dopamine transporter binding sites in mice following treatment
      with the TIQ analogue 1-benzyl-1,2,3,4-tetrahydroisoquinoline.
AB  - 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) and TIQ are endogenous
      substances inducing bradykinesia, one of the symptoms of parkinsonism, in rodents
      and primates, and 2-methyl-TIQ is postulated to be an active form of TIQ. We
      investigated the effect of 1-BnTIQ-, TIQ- or 2-methyl-TIQ-treatment on the
      binding of 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-[N-methyl-11C]tropane to
      striatal dopamine transporters (DATs) in mice. Neither 1-BnTIQ (80 mg/kg, i.p.,
      twice per day for 10 days) nor 2-methyl-TIQ (40 mg/kg, i.p., twice per day for 10
      days) affected the radioligand-DAT binding, while TIQ (80 mg/kg, i.p., twice per
      day for 10 days) induced a 14% decrease. These results indicate that 1-BnTIQ does
      not affect the density of DATs on dopaminergic neurons, and that it is not clear
      whether or not 2-methyl-TIQ is an active form of TIQ.

PMID- 12505686
TI  - Cannabinergic ligands.
AB  - The understanding of the pharmacology surrounding the cannabinergic system has
      seen many advances since the discovery of the CB1 receptor in the mammalian brain
      and the CB2 receptor in the periphery. Among these advances is the discovery of
      the endogenous ligands arachidonoylethanolamide (anandamide) and 2
      arachidonoylglycerol amide (2-AG), which are selective agonists for the CB1 and
      CB2 receptors, respectively. These endogenous neuromodulators involved in the
      cannabinergic system are thought to be produced on demand and are metabolized by
      the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAG
      lipase). Recently, we characterized a reuptake system that facilitates the
      transport of anandamide across the cell membrane and subsequently developed
      selective inhibitors of this transport, which have been found to have therapeutic
      potential as analgesic and peripheral vasodilators. The cannabinergic proteins
      currently being explored, which include the CB1 and CB2 receptors, FAAH and the
      anandamide transporter, are excellent targets for the development of
      therapeutically useful drugs for a range of conditions including pain, loss of
      appetite, immunosuppression, peripheral vascular disease and motor disorders. As
      cannabinoid research has progressed, various potent and selective cannabimimetic
      ligands, targeting these four cannabinoid proteins, have been designed and
      synthesized. Many of these ligands serve as important molecular probes, providing
      structural information regarding the binding sites of the cannabinergic proteins,
      as well as pharmacological tools, which have been playing pivotal roles in
      research aimed at understanding the biochemical and physiological aspects of the
      endocannabinoid system. This review will focus on some of the current
      cannabinergic ligands and probes and their pharmacological and therapeutic
      potential.

PMID- 12505687
TI  - Recent advances in the synthesis of endocannabinoid related ligands.
AB  - The chemical strategies used for the synthesis of various ligands related to the
      endocannabinoid system namely anandamide (AEA), 2-arachidonylglycerol (2-Ara-Gl),
      CB1/(vanilloid receptors) VR1, anandamide membrane transporter (AMT) and fatty
      acid amide hydrolase (FAAH) are described in this review. In general, the
      chemical synthesis of analogs with changes in the head group of AEA was quite
      straightforward involving the conversion of an acid to an amide or an ester.
      Analogs which had modifications in the end pentyl chain were more difficult to
      synthesize and required multistep synthetic sequences to prepare the target
      compounds. A facile total synthesis of 2-Ara-Gl was reported and an HPLC
      procedure for its identification and quantification was developed, but because of
      the instability of 2-Ara-Gl another synthesis was developed so that it can be
      stored as the more stable phenylboronate ester. Similarly the chemical synthesis
      of various ligands in the remaining areas of CB1/VR1, AMT and FAAH are described.
      A summary of the present state of knowledge about the SAR in each area is
      presented to help in the design and synthesis of novel ligands for the future.

PMID- 12505688
TI  - Cannabidiol: an overview of some chemical and pharmacological aspects. Part I:
      chemical aspects.
AB  - Over the last few years considerable attention has focused on cannabidiol (CBD),
      a major non-psychotropic constituent of Cannabis. In Part I of this review we
      present a condensed survey of the chemistry of CBD; in Part II, to be published
      later, we shall discuss the anti-convulsive, anti-anxiety, anti-psychotic, anti
      nausea and anti-rheumatoid arthritic properties of CBD. CBD does not bind to the
      known cannabinoid receptors and its mechanism of action is yet unknown. In Part
      II we shall also present evidence that it is conceivable that, in part at least,
      its effects are due to its recently discovered inhibition of anandamide uptake
      and hydrolysis and to its anti-oxidative effect.

PMID- 12505689
TI  - The quest for a vascular endothelial cannabinoid receptor.
AB  - This review examines pharmacological and biochemical evidence that suggests the
      existence of an as yet undefined endothelial receptor that mediates
      endocannabinoid-induced vasodilation. The signaling mechanisms triggered through
      this receptor and its potential physiological role are also discussed. Since
      vasodilation is often associated with hypotension, mechanisms involved in the
      hypotensive actions of cannabinoids, including the endocannabinoids anandamide
      and 2-arachidonoylglycerol, are also briefly reviewed.

PMID- 12505690
TI  - Cannabinoid pharmacology: implications for additional cannabinoid receptor
      subtypes.
AB  - Delta(9)-Tetrahydrocannabinol (delta(9)-THC), the primary psychoactive
      constituent of marijuana (Cannabis sativa), is known to bind to two cannabinoid
      receptors: CB(1) receptors, located primarily in the brain, and CB(2) receptors,
      located primarily in the periphery. Recent research has suggested that other
      cannabinoids, including anandamide and WIN 55212-2, may also act at novel non
      CB(1), non-CB(2) cannabinoid receptor(s). Anandamide produces a number of in vivo
      pharmacological effects in CB(1) knockout mice that are not produced by delta(9)
      THC and cannot be explained by anandamide's rapid metabolism. In addition, in
      vitro anandamide and WIN 55212-2 stimulate [35S]GTPgammaS binding in both CB(1)
      knockout and wildtype mice while delta(9)-THC stimulates this binding only in
      wildtype mice. Although anandamide and vanilloid agonists share pharmacological
      effects, anandamide's actions in CB(1) knockout mice do not appear to be mediated
      by vanilloid VR(1) receptors. While not yet conclusive, these results suggest the
      possibility of additional cannabinoid receptors in the brain and periphery.

PMID- 12505691
TI  - In vivo imaging of the brain cannabinoid receptor.
AB  - The CB1 cannabinoid receptor is expressed in the brain at levels sufficient to
      serve as potential target for in vivo imaging using positron emission tomography
      (PET) or single photon emission computed tomography methodology. To date, the
      most promising radioligands for the in vivo imaging of this receptor have
      structures based on that of the cannabinoid antagonist, SR141716A. Rodent data
      obtained using these in vivo radiotracers has demonstrated that both the
      behavioral and neurochemical effects of cannabinoids occur at very low levels of
      receptor occupancy. More recently, an agonist radiotracer based on the structure
      of aminoalkylindole cannabinoids has also been examined for in vivo labeling of
      CB1 receptors. Although rodent studies have indicated that in vivo imaging of CB1
      receptors is feasible, at the present time this receptor has still to be
      successful imaged in a human PET study.

PMID- 12505692
TI  - Distinct cannabinoid sensitive receptors regulate hippocampal excitation and
      inhibition.
AB  - One of the well-known effects of cannabinoids is the impairment of cognitive
      processes, including short-term memory formation, by altering hippocampal and
      neocortical functions reflected in network activity. Acting on presynaptically
      located G protein-coupled receptors in the hippocampus, cannabinoids modulate the
      release of neurotransmitter molecules. CB1 cannabinoid receptors, so far the only
      cloned cannabinoid receptor type in the CNS, are selectively expressed on the
      axon terminals of a subset of GABAergic inhibitory interneurons containing the
      neuropeptide cholecystokinin. Activation of CB1 receptors reduces GABA release
      from presynaptic terminals, thereby increasing the excitability of principal
      cells. Novel, non-CB1 cannabinoid sensitive receptors are present on the
      hippocampal excitatory axon terminals, which suppress glutamate release. These
      cannabinoid receptors have distinct pharmacological features compared to CB1,
      i.e. WIN 55212-2 is an order of magnitude less potent in reducing glutamatergic
      transmission than in inhibiting GABAergic postsynaptic currents, and the novel
      receptor binds vanilloid receptor ligands. Thus, at least two different
      cannabinoid sensitive presynaptic receptors regulate network activity in the
      hippocampus, CB1 via the GABAergic interneurons, and a new receptor via a direct
      action on pyramidal cell axon terminals.

PMID- 12505693
TI  - Dimerization of G protein-coupled receptors: CB1 cannabinoid receptors as an
      example.
AB  - A polyclonal antibody directed towards the last 73 amino acid residues of the rat
      type 1 cannabinoid (CB1) receptor strongly and exclusively labels a high
      molecular weight (between 160 and 200 kDa) form of the receptor in Western
      analysis. In contrast, a human CB1 polyclonal antibody identifies both monomeric
      CB1 as well as the high molecular weight form. The carboxy terminus (CT) antibody
      was also used in immunocytochemistry of rat hippocampal sections. Sections probed
      with CT antibody show intense staining of a meshwork of fibers and occasional
      interneurons of the stratum oriens, stratum pyramidal, and stratum radiatum of
      the CA1 and CA3 regions while mossy fibers and granule cells of the internal
      stratum appear unstained. These data provide evidence that CB1 likely exists as a
      dimer in vivo and that the carboxy end of the receptor may play a role in the
      assembly of the oligomer.

PMID- 12505694
TI  - CB(1) cannabinoid receptor-G protein association: a possible mechanism for
      differential signaling.
AB  - Effects of cannabinoid compounds on neurons are predominantly mediated by the
      CB(1) cannabinoid receptor. Onset of signaling cascades in response to
      cannabimimetic drugs is triggered by the interaction of the cannabinoid receptor
      with G(i/o) proteins. Much work has been done to delineate the cannabinoid
      agonist-induced downstream signaling events; however, it remains to define the
      molecular basis of cannabinoid receptor-G protein interactions that stimulate
      these signaling pathways. In this review, we discuss several signal transduction
      pathways, focusing on studies that demonstrate the efficacy of CB(1) receptor
      agonists through G protein mediated pathways.

PMID- 12505695
TI  - Cell signaling by endocannabinoids and their congeners: questions of selectivity
      and other challenges.
AB  - The major endocannabinoids, anandamide (N-arachidonoylethanolamide, 20:4n-6 N
      acylethanolamine) and 2-arachidonoylglycerol (2-AG) are structurally and
      functionally similar, but they are produced by different metabolic pathways and
      their levels must therefore be regulated by different mechanisms. Both
      endocannabinoids are accompanied by cannabinoid receptor-inactive, saturated and
      mono- or di-unsaturated congeners which can influence their metabolism and
      function. Here we review published data on the presence and production of
      anandamide and 2-AG and their congeners in mammalian cells and discuss this
      information in terms of their proposed signaling functions.

PMID- 12505696
TI  - The enzymatic inactivation of the fatty acid amide class of signaling lipids.
AB  - The fatty acid amide (FAA) class of signaling lipids modulates a number of
      neurobehavioral processes in mammals, including pain, sleep, feeding, and
      locomotor activity. Representative FAAs include the endogenous cannabinoid
      anandamide and the sleep-inducing lipid oleamide. Despite activating several
      neuroreceptor systems in vitro, most FAAs produce only weak and transient
      behavioral effects in vivo, presumably due to their expeditious catabolism. This
      review focuses on one enzyme, fatty acid amide hydrolase (FAAH) that appears to
      play a major role in regulating the amplitude and duration of FAA signals in
      vivo. In particular, we will highlight a series of recent papers that have
      investigated the physiological functions of the mouse and human FAAH enzymes.
      Collectively, these studies promote FAAH as a central component of FAA signaling
      pathways, especially those mediated by the endocannabinoid anandamide, and
      suggest that this enzyme may represent an attractive pharmaceutical target for
      the treatment of pain and related neurophysiological disorders.

PMID- 12505697
TI  - A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation.
AB  - 2-Arachidonoylglycerol (2-AG) is a naturally occurring monoglyceride that
      activates cannabinoid receptors and meets several key requisites of an endogenous
      cannabinoid substance. It is present in the brain (where its levels are 170-folds
      higher than those of anandamide), is produced by neurons in an activity- and
      calcium-dependent manner, and is rapidly eliminated. The mechanism of 2-AG
      inactivation is not completely understood, but is thought to involve carrier
      mediated transport into cells followed by enzymatic hydrolysis. We examined the
      possible role of the serine hydrolase, monoglyceride lipase (MGL), in brain 2-AG
      inactivation. We identified by homology screening a cDNA sequence encoding for a
      303-amino acid protein, which conferred MGL activity upon transfection to COS-7
      cells. Northern blot and in situ hybridization analyses revealed that MGL mRNA is
      unevenly present in the rat brain, with highest levels in regions where CB1
      cannabinoid receptors are also expressed (hippocampus, cortex, anterior thalamus
      and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL
      distribution has striking laminar specificity, suggesting a presynaptic
      localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat
      cortical neurons increased the degradation of endogenously produced 2-AG in these
      cells, whereas no such effect was observed on anandamide degradation. These
      results indicate that hydrolysis via MGL may be a primary route of 2-AG
      inactivation in intact neuronal cells.

PMID- 12505698
TI  - Endocannabinoids and related fatty acid derivatives in pain modulation.
AB  - The brain produces at least five compounds that possess sub-micromolar affinity
      for cannabinoid receptors: anandamide, 2-arachidonoylglycerol, noladin ether,
      virodhamine, and N-arachidonoyldopamine (NADA). One function of these and/or
      related compounds is to suppress pain sensitivity. Much evidence supports a role
      of endocannabinoids in pain modulation in general, and some evidence points to
      the role of particular endocannabinoids. Related endogenous fatty acid
      derivatives such as oleamide, palmitoylethanolamide, 2-lineoylglycerol, 2
      palmitoylglycerol, and a family of arachidonoyl amino acids may interact with
      endocannabinoids in the modulation of pain sensitivity.

PMID- 12505699
TI  - Spinal and peripheral mechanisms of cannabinoid antinociception: behavioral,
      neurophysiological and neuroanatomical perspectives.
AB  - A large body of literature indicates that cannabinoids suppress behavioral
      responses to acute and persistent noxious stimulation. This review examines
      behavioral, neurophysiological and neuroanatomical evidence supporting a role for
      cannabinoids in suppressing nociceptive transmission at spinal and peripheral
      levels. The development of subtype-selective competitive antagonists and high
      affinity agonists provides the pharmacological tools required to study
      cannabinoid antinociceptive mechanisms. These studies provide insight into the
      functional roles of cannabinoid receptor subtypes, CB1 and CB2, in cannabinoid
      antinociceptive mechanisms as revealed in animal models of acute and persistent
      (somatic inflammatory, visceral inflammatory, neuropathic) pain. Localization
      studies employing receptor binding and quantitative autoradiography,
      immunocytochemistry and in situ hybridization are reviewed to examine the
      distribution of cannabinoid receptors at these levels and provide a
      neuroanatomical framework with which to understand the roles of endogenous
      cannabinoids in sensory processing.

PMID- 12505700
TI  - Inhibition of pain responses by activation of CB(2) cannabinoid receptors.
AB  - Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive
      evidence demonstrates that CB(1) cannabinoid receptor activation inhibits pain
      responses. Recently, the synthesis of CB(2) cannabinoid receptor-selective
      agonists has allowed testing whether CB(2) receptor activation inhibits pain.
      CB(2) receptor activation is sufficient to inhibit acute nociception,
      inflammatory hyperalgesia, and the allodynia and hyperalgesia produced in a
      neuropathic pain model. Studies using site-specific administration of agonist and
      antagonist have suggested that CB(2) receptor agonists inhibit pain responses by
      acting at peripheral sites. CB(2) receptor activation also inhibits edema and
      plasma extravasation produced by inflammation. CB(2) receptor-selective agonists
      do not produce central nervous system (CNS) effects typical of cannabinoids
      retaining agonist activity at the CB(1) receptor. Peripheral antinociception
      without CNS effects is consistent with the peripheral distribution of CB(2)
      receptors. CB(2) receptor agonists may have promise for the treatment of pain and
      inflammation without CNS side effects.

PMID- 12505701
TI  - Endocannabinoid signaling in synchronizing embryo development and uterine
      receptivity for implantation.
AB  - There are reports of adverse effects of cannabinoids on pregnancy outcome
      including retarded embryo development and pregnancy failure. Thus, discoveries of
      endogenous cannabinoid-like lipid mediators and cannabinoid receptors raise
      questions about their pathophysiological roles during normal pregnancy. We
      previously reported that anandamide, an endogenously produced arachidonate
      derivative (endocannabinoid), is synthesized in the female reproductive tracts,
      and it acts on cannabinoid receptors expressed on the cell surface of the embryo
      to regulate the preimplantation embryo development and implantation in mice. This
      review presents genetic, molecular, physiological and pharmacological evidence
      that the levels of uterine anandamide and blastocyst CB1 cannabinoid receptors
      are coordinately regulated to synchronize preimplantation development and uterine
      receptivity for implantation in mice.

PMID- 12505702
TI  - N-Acylethanolamines in human reproductive fluids.
AB  - N-Acylethanolamines (NAEs) are an important family of lipid-signaling molecules.
      Arachidonylethanolamide (anandamide) (AEA), palmitoylethanolamide (PEA), and
      oleoylethanolamide (OEA) are co-produced from similar phospholipid precursors
      when neurons are stimulated. AEA is an endogenous agonist (endocannabinoid) for
      cannabinoid receptors. It binds with higher affinity to type CB1 than to type CB2
      cannabinoid receptors. PEA does not bind to CB1, while the hypothesis that it
      reacts with putative CB2-like receptors has been questioned. OEA does not
      activate currently known cannabinoid receptors, but it mimics the effects of AEA
      and cannabinoids in reducing the fertilizing capacity of sea urchin sperm. OEA
      and PEA also act as entourage compounds by inhibiting the hydrolysis of AEA by
      fatty acid amide hydrolase. Cannabinoid receptors and/or AEA are present in
      mammalian reproductive organs including the testis, epididymis, prostate, ovary,
      uterus, sperm, preimplantation embryo and placenta, as well as prostatic and
      mammary carcinomas. We now report that analysis by high-performance liquid
      chromatography/mass spectrometry (HPLC/MS) shows the presence of AEA, PEA, and
      OEA in human seminal plasma, mid-cycle oviductal fluid, follicular fluid,
      amniotic fluid, milk, and fluids from malignant ovarian cysts. Previous studies
      showed that AEA-signaling via cannabinoid receptors regulates capacitation and
      fertilizing potential of human sperm, early embryonic development and blastocyst
      implantation into the uterine mucosa of rodents, as well as proliferation of
      human mammary and prostatic carcinomas. Current results imply that NAEs also may
      modulate follicular maturation and ovulation, normal and pathological ovarian
      function, placental and fetal physiology, lactation, infant physiology, and
      behavior. Collectively, these findings suggest that NAEs in human reproductive
      fluids may help regulate multiple physiological and pathological processes in the
      reproductive system, and imply that exogenous cannabinoids delivered by marijuana
      smoke might impact these processes. This study has potential medical and public
      policy ramifications because of the incidence of marijuana abuse by adolescents
      and adults in our society, previously documented reproductive effects of
      marijuana, and the ongoing debate about medicinal use of marijuana and
      cannabinoids.

PMID- 12505703
TI  - Effects of delta-9-tetrahydrocannabinol on human immune function and host
      defense.
AB  - This review examines evidence that delta(9)-tetrahydrocannabinol (THC) can
      regulate and suppress human immune responses. Leukocytes express both cannabinoid
      receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), and levels of mRNA
      encoding for them are increased in peripheral blood leukocytes obtained from
      marijuana smokers, suggesting cannabinoid receptor activation in vivo. Exposure
      of human T-cells to THC suppresses their proliferation, inhibits the release of
      interferon-gamma, and skews the balance of T-helper cytokines towards a type 2
      response. The majority of these effects are CB2 receptor-dependent. Consistent
      with an impact of THC on cell-mediated immunity, alveolar macrophages (AMs)
      recovered from the lungs of marijuana smokers are suppressed in their ability to
      release pro-inflammatory cytokines and nitric oxide (NO), and kill bacteria.
      Macrophage function is restored by treatment with interferon-gamma, a type 1
      cytokine. Habitual exposure to THC appears capable of impacting on human cell
      mediated immunity and host defense.

PMID- 12505704
TI  - Gene expression profiling: methodological challenges, results, and prospects for
      addiction research.
AB  - This review describes the current methods used to profile gene expression. These
      methods include microarrays, spotted arrays, serial analysis of gene expression
      (SAGE), and massive parallel signature sequencing (MPSS). Methodological and
      statistical problems in interpreting microarray and spotted array experiments are
      also discussed. Methods and formats such as minimum information about microarray
      experiments (MIAME) needed to share gene expression data are described. The last
      part of the review provides an overview of the application of gene-expression
      profiling technology to substance abuse research and discusses future directions.

PMID- 12505705
TI  - Assessment of cannabinoid induced gene changes: tolerance and neuroprotection.
AB  - The analysis of gene changes associated with exposure to cannabinoids is critical
      due to the multiple possible signaling pathways potentially affected by
      cannabinoid receptor activation. A comparison of altered gene profiles under two
      different conditions, one in vivo (chronic exposure to delta-9-THC) and the other
      in vitro (neuroprotection mediated by WIN55212-2), was made to determine whether
      it was possible to identify common genes that were affected. Up and down
      regulated sets of genes are described. Genes affected in one or the other
      circumstance include alterations in a 14-3-3 regulator protein of PKC, CREB, BDNF
      and GABA receptor subunit proteins, as well as several genes associated with
      known cannabinoid receptor-coupled signaling pathways. Unexpectedly, several
      genes that were altered in both circumstances were associated with synaptic and
      membrane structure, motility and neuron growth. These included, neuronal cell
      adhesion molecule (NCAM), hyloronidan motility receptor, and myelin proteolipid
      protein. While the basis for involvement of these particular genes in cannabinoid
      receptor activated functional processes within the cell is still not well
      understood, awareness that significant numbers of genes and presumably proteins
      are changed following either acute or long-term exposure may provide new insight
      into their effects.

PMID- 12505706
TI  - Addictive potential of cannabinoids: the underlying neurobiology.
AB  - Drugs that are addictive in humans have a number of commonalities in animal model
      systems-(1). they enhance electrical brain-stimulation reward in the core meso
      accumbens reward circuitry of the brain, a circuit encompassing that portion of
      the medial forebrain bundle (MFB) which links the ventral tegmental area (VTA) of
      the mesencephalic midbrain with the nucleus accumbens (Acb) of the ventral limbic
      forebrain; (2). they enhance neural firing of a core dopamine (DA) component of
      this meso-accumbens reward circuit; (3). they enhance DA tone in this reward
      relevant meso-accumbens DA circuit, with resultant enhancement of extracellular
      Acb DA; (4). they produce conditioned place preference (CPP), a behavioral model
      of incentive motivation; (5). they are self-administered; and (6). they trigger
      reinstatement of drug-seeking behavior in animals behaviorally extinguished from
      intravenous drug self-administration behavior and, perforce, pharmacologically
      detoxified from their self-administered drug. Cannabinoids were long considered
      'anomalous', in that they were believed to not interact with these brain reward
      processes or support drug-seeking and drug-taking behavior in these animal model
      systems. However, it is now clear-from the published data of several research
      groups over the last 15 years-that this view of cannabinoid action on brain
      reward processes and reward-related behaviors is untenable. This paper reviews
      those data, and concludes that cannabinoids act on brain reward processes and
      reward-related behaviors in strikingly similar fashion to other addictive drugs.

PMID- 12505707
TI  - Idiotype-anti-idiotype-based noncompetitive enzyme-linked immunosorbent assay of
      ursodeoxycholic acid 7-N-acetylglucosaminides in human urine with subfemtomole
      range sensitivity.
AB  - We have established a noncompetitive enzyme-linked immunosorbent assay (ELISA)
      for the group-specific determination of 7-N-acetylglucosaminide of
      ursodeoxycholic acid (UDCA 7-NAG) and its glycine- and taurine-amidated
      metabolites (UDCA 7-NAGs) in human urine. These metabolites are expected to be a
      diagnostic marker for patients with primary biliary cirrhosis (PBC). This assay
      is based on the idiotype-antiidiotype reaction where the analyte was captured by
      an excess amount of anti-UDCA 7-NAG antibody, and the unoccupied paratope was
      blocked with a beta-type antiidiotype antibody. The hapten-occupied antibody was
      then selectively detected with a biotin-labeled alpha-type antiidiotype antibody.
      The amount of bound biotin, increasing proportionally to the increase in the
      analyte, was colorimetrically determined using a peroxidase-labeled streptavidin.
      This assay provided subfemtomole range sensitivity (detection limit 118 amol) and
      allowed group-specific measurement of the UDCA 7-NAGs in urine without any
      pretreatment. The present ELISA revealed that significant amounts of UDCA 7-NAGs
      are excreted even in healthy subjects. Daily excretion rates for healthy males
      were determined to be 246+/-184 (S.D.) microg (n=5) as the glycine-amidated UDCA
      7-NAG equivalent. Randomly collected urine specimens from patients with PBC (n=7)
      were also measured, and the assay values (standardized to creatinine excretion)
      ranged from 1.82 to 13.4 microg/mg Ucre with the average of 5.41+/-4.53 (S.D.)
      microg/mg Ucre.

PMID- 12505708
TI  - Delay in processing porcine whole blood affects cytokine expression.
AB  - Quantification of cytokine messenger ribonucleic acid (mRNA) in blood samples has
      become an important tool in the investigation of immune cell activation in a
      variety of clinical settings. It has been shown that the method of sample
      collection and processing influences the levels of several cytokine mRNAs.
      Therefore, it is generally accepted that blood samples for analysis of cytokine
      expression be processed as soon as possible and under standardised conditions.
      Since immediate sample processing is not always possible, we investigated the
      effect of different storage conditions (room temperature (Rt) and 4 degrees C)
      and storage times (1, 2, 4, 6 and 24 h) on the mRNA level of different cytokines
      (IL-1alpha, IL-2, IL-6, IL-8, IL-10, IFN-gamma), as well as the IL-2 receptor (IL
      2R) in porcine whole blood samples (n=8). Quantification of cytokine expression
      was performed using simultaneous reverse transcription PCR (RT-PCR) combined with
      the expression of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) as a reference. Our data demonstrate that delays in sample processing
      longer than 1 h result in significant changes of the mRNA levels of individual
      cytokines. Expression of the monokines IL-1alpha, IL-6 and IL-10 were increased
      by storage at both room temperature and 4 degrees C. Expression of IL-8 was
      increased only in the samples stored at room temperature, and expression of IFN
      gamma was raised exclusively in the samples stored at 4 degrees C. We conclude
      that porcine blood samples should be processed within 2 h to prevent undesired
      stimulatory effects on the cytokine expression pattern. However, if only selected
      cytokines are investigated, the undesired effects of prolonged storage can be
      selectively suppressed by choosing the appropriate temperature of sample storage.

PMID- 12505709
TI  - A systematic comparison of methods to measure HIV-1 specific CD8 T cells.
AB  - Several methods are now available to evaluate the frequencies of virus-specific
      CD8 T cells but require a systematic comparison to help at choosing the best
      strategy for evaluation. First, we compared the ELISpot-IFNgamma assay,
      intracellular IFNgamma staining and HLA class I tetramer-binding assay to
      quantify the HIV-specific CD8 T cells. Second, we determined the frequency of
      recognition of HIV antigens and evaluated whether the mode of antigen
      presentation might influence the results: We compared HIV antigen presentation in
      the same ELISpot-IFNgamma assays by using recombinant vaccinia viruses (rVVs)
      encoding for HIV-LAI Gag, Pol, Env, Nef, Tat and Vif proteins, or a panel of 49
      synthetic 8-11 amino acid length peptides tested either individually or pooled.
      Third, we compared the antigens recognized by memory CTL analysis using chromium
      release assay (CRA) on CTL lines and by effector CD8 cell analysis using ELISpot
      assay. Our results show that: (1) Flow cytometry and ELISpot assay measuring
      IFNgamma production give the same frequency of HIV-specific CD8 T cells; (2)
      tetramer-binding assay detects more HIV-specific CD8 T cells than other methods;
      (3) pools of optimal peptides and sum frequencies of individual optimal peptides
      give similar results in ELISpot assay; (4) ELISpot assays using peptides are more
      sensitive than those using rVV; and (5) CRA and ELISpot assay when using rVV
      provide a comparable profile of HIV antigen recognition by memory CTLs (CRA) and
      effector CTLs (ELISpot) in two thirds cases. These results have important
      implications for the choice of immunological methods to evaluate CD8 T cells
      responses to vaccines.

PMID- 12505710
TI  - Cryopreservation of immature monocyte-derived dendritic cells results in enhanced
      cell maturation but reduced endocytic activity and efficiency of adenoviral
      transduction.
AB  - To date, phase I/II dendritic cell (DC)-based cancer vaccine trials have required
      repeated venesection or leukapheresis to generate the DCs. Previous studies have
      suggested that DCs may be cryopreserved and revived for clinical use as
      sequential immunisations. We have developed a method of cryopreserving monocyte
      derived DCs, reviving the cells with minimal loss, and have performed
      immunophenotypic and functional comparisons of freeze-thawed DCs with their fresh
      counterparts. We found that the freeze-thawing process itself is efficient in
      terms of DC recovery, results in semimaturation and reduced endocytic activity,
      but does not impair the capacity of the DCs to achieve full maturation. Revived
      cells also showed enhanced allostimulatory activity and antigen-specific
      responses. After freeze-thawing, DCs produced lower levels of IL-12 p40 and IL-12
      p70 on maturation compared to fresh DCs with little change in concentration over
      72 h. Genetic modification of DCs by adenoviral transduction was possible after
      cryopreservation albeit at a lower efficiency of gene transfer than with fresh
      cells. We conclude that cryopreservation of DCs for clinical immunotherapy is
      feasible. Modification of cells by pulsing or genetic transfer should take place
      prior to cryopreservation as the freeze-thawing process itself leads to increased
      maturation, reduction in endocytic activity but enhanced allostimulatory activity
      and antigen-specific responses.

PMID- 12505711
TI  - A rapid immunohistochemical primary screening assay for hybridomas.
AB  - A primary screening of monoclonal antibodies (mAbs) prepared by hybridoma
      technology requires the testing of a large number of hybridoma culture
      supernatants within a short time. In addition, the intended application of the
      mAbs (e.g. ELISA, immunoblot, neutralization, histochemistry) have to be
      considered when selecting the optimal screening procedure. We have developed a
      rapid micromethod for the primary screening of mAbs which permits the selection
      of antibodies suitable for immunohistochemistry in a single step. This method
      combines the capacity of an assay performed in 96-well plates and the specificity
      of a microscopic immunohistochemical technique. The capacity of classical
      immunohistochemical methods working with glass slides is limited to tens of
      preparations, but the improved screening micromethod allows the processing of
      hundreds of culture supernatants in one single round of the assay. The
      suitability of this novel screening system was established by the selection of
      mAbs recognising Alzheimer's disease (AD)-neurofibrillary pathology in
      histological preparations and phosphoprotein pp32 in rat brain sections.

PMID- 12505712
TI  - IFN-gamma bioassay: development of a sensitive method by measuring nitric oxide
      production by peritoneal exudate cells from C57BL/6 mice.
AB  - Interferon-gamma (IFN-gamma) is an important immunomodulatory and pleiotropic
      cytokine produced, primarily, by activated T lymphocytes and natural killer (NK)
      cells. We have devised a nitric oxide (NO)-based bioassay for mouse IFN-gamma
      using resident peritoneal exudate cells (PECs) from C57BL/6 mice. Comparison with
      three existing bioassays demonstrated that this assay was very sensitive and
      detected IFN-gamma in the linear range of approximately 0.03-0.25 U/ml. Other
      cytokines, e.g. interleukin (IL)-2, IL-4, IL-6, IFN-alpha/beta and tumor necrosis
      factor-alpha (TNF-alpha), either alone or in combination with IFN-gamma, did not
      greatly modulate NO levels produced by resident peritoneal exudate cells. The
      presence of exogenous NO(3)(-) and H(2)O(2) did not interfere with the IFN-gamma
      induced NO production and detection. We also showed that the effect of
      lipopolysaccharide (LPS), which may be present in samples, could be suppressed by
      the use of Polymyxin B in the bioassay. The high sensitivity of the bioassay
      permitted the detection of low amounts of IFN-gamma in 1% mouse serum. In
      addition, this assay reproducibly detected bioactive IFN-gamma amounts in
      supernatants of activated T cells. The increase in IFN-gamma production by
      activated T cells in response to CD28 costimulation was approximately 3-fold by
      this bioassay and approximately 5-fold by ELISA. In summary, we have devised a
      simple, sensitive, inexpensive and high throughput method for the reproducible
      detection of bioactive IFN-gamma.

PMID- 12505713
TI  - A novel micro-cell-mediated lympholytic assay for the evaluation of regulatory
      cells in human alloreactive CTL responses.
AB  - Since cell-mediated lympholysis (CML), the most commonly used in vitro
      experimental cytotoxic method for the evaluation of regulatory cells, requires
      large numbers of cells that are often the limiting factor, we have developed a
      new micro-cell-mediated lympholytic (m-CML) assay. Various numbers of responding
      cells were stimulated with equivalent numbers of allogeneic irradiated stimulator
      cells in the presence of (fivefold) serial dilutions of regulatory cells. On the
      8th day, 4-h 51Cr-release assays were performed by adding 5000 labeled target
      cells from the corresponding stimulators to the cultures. Even though results
      that were comparable to the macro- (bulk) CML and MLR modulation experiments were
      obtained with all the cell combinations tested in the m-CML, the combinations
      with 50,000 responder cells and stimulating cells and dilutions of 25,000 to 40
      modulator (regulatory) cells were found to be the most reproducible for assaying
      regulatory cell potency in vitro. Similarly, expression of the results as
      percentage inhibition using percent specific lysis values was the simplest method
      of calculation. This assay was standardized for the evaluation of the inhibitory
      activity of a variety of regulatory cells, including long-term cultures of
      cadaver-donor vertebral body bone marrow cells (vDBMC-L), in vitro generated CD8
      positive and CD28 negative suppressor T cells and donor chimeric cells isolated
      from renal transplant recipients who had been perioperatively infused with donor
      bone marrow cells (DBMC). The results indicate that the m-CML assay is a
      sensitive and reliable micromethod with at least 10-fold fewer responders,
      stimulator and modulator cell numbers needed than macro-CML assays for the
      evaluation of regulatory cells obtained from a variety of immune systems in
      vitro.

PMID- 12505714
TI  - Monitoring E-selectin-mediated adhesion using green and red fluorescent proteins.
AB  - Accumulating evidence suggests that E-selectin, which is physiologically involved
      in leukocyte recruitment during inflammation, plays an important role in the
      early stages of tumor cell interactions with vessel walls and contributes to the
      hematogenous spreading of cancer cells. Therapy designed to block this key step
      may provide an effective anti-inflammatory and anti-metastatic treatment. It is
      therefore critical to establish a safe, rapid and sensitive E-selectin adhesion
      assay. In this regard, we propose a simple and highly sensitive adhesion system
      based on CHO cells permanently co-expressing E-selectin and the enhanced green
      fluorescent protein EGFP or the red fluorescent protein DsRed2. This is an
      inverted adhesion assay in which tumor cells are maintained intact while
      fluorescent cells expressing E-selectin and EGFP (or DsRed2) are added to them.
      Adherent cells are then quantified by three different fluorescence-based
      techniques including spectrofluorimetry, ELISA-type cytofluorimetry and
      fluorescence microscopy coupled to digital image quantification. In this assay, a
      battery of cell lines can be analysed at once since only one cell line
      (fluorescent E-selectin-expressing cells) needs to be harvested. We used this
      approach to analyze a number of E-selectin-specific binding parameters of
      intestinal cancer cells in comparison with adhesion to activated endothelial
      cells or to plastic dishes coated with recombinant E-selectin. Besides the
      possibility of analyzing a battery of cell lines at once, this assay might be
      suitable for screening anti-metastatic compounds and could provide valuable
      information on the metastatic potential of human cancers.

PMID- 12505715
TI  - Structural correlates of a functional streptokinase antigenic epitope: serine 138
      is an essential residue for antibody binding.
AB  - We determined the pattern of cross-reactivity of a panel of anti-streptokinase
      (SK) monoclonal antibodies (mAbs) with SK variants in order to map the antigenic
      and functional epitope of SK. Comparison of the pattern of cross-reactivity of
      the anti-SK mAb A4.3 with SK variants and sequence alignments of SK variants and
      native (n) SK suggested that mutation of Ser 138 to Lys results in loss of
      binding of mAb A4.3 to SK variants. However, this mutation does not affect
      formation of activator complex by these proteins. The epitope specificity of the
      mAb A4.3 was further confirmed by mutating Ser 138 to Lys in n SK. Monoclonal Ab
      A4.3 did not bind to mutant SK (Ser138Lys). Activator activity of mutant SK
      (Ser138Lys) was indistinguishable from that of n SK and recombinant n SK. Since
      addition of A4.3 mAb to an equimolar mixture of SK and human plasminogen inhibits
      activator complex formation, the sequences spanning position 138 are likely
      important for formation of streptokinase-plasminogen activator complex or
      processing of the plasminogen substrate.

PMID- 12505716
TI  - Monoclonal antibodies as a probe for the unfolding of porcine growth hormone.
AB  - Monoclonal antibodies (mAbs) were generated against pituitary porcine growth
      hormone (pGH). Ten mAbs were selected for their specificity and affinity for pGH.
      These mAbs were of the immunoglobulin G (IgG)(1) kappa subclass, with
      dissociation constants (K(d)) between 7.42 and 0.26 nM, and recognised seven non
      overlapping epitopes. We measured whether the mAbs detected alterations of the
      pGH three-dimensional structure by comparing the antibody reactivity to native
      pGH and to pGH experimentally unfolded by heating at 50 degrees C, 75 degrees C
      and 100 degrees C or by reduction and S-carboxymethylation. The antibody-antigen
      interactions were studied with two enzyme-linked immunosorbent assays (ELISA),
      based either on a direct binding or inhibition format. The results show that: 1)
      one mAb, mAb D12, is a conformation-sensitive antibody that recognises an epitope
      present only in the native pGH. Because the intact three-dimensional structure is
      essential for the expression of biological activity, mAb D12 could be used to
      detect altered pGH molecules in biological samples (blood, pituitary extracts or
      material produced with recombinant technology), and for the one-step purification
      of biologically active pGH by immunoaffinity chromatography; 2) one mAb, mAb I4,
      binds to a linear epitope that is not significantly modified in the denatured
      hormone. This mAb was able to detect the hormone in assays where protein
      conformation is usually strongly altered, i.e. immunoblotting and
      immunohistochemistry; 3) the performances of the other eight mAbs differed
      significantly in the competitive and non-competitive ELISA.

PMID- 12505717
TI  - A liver perfusion model for studies of selective adherence and transient halting
      of portal blood leukocytes in sinusoids.
AB  - Portal blood leukocytes play an important, but still poorly defined, role in the
      immune processes of the liver. In our previous studies, we showed that certain
      leukocyte subsets are selectively halted in the liver. These cells marginate in
      sinusoids and, together with resident Kupffer and endothelial sinusoidal cells,
      participate in antiviral and antitumor processes. The molecular mechanisms of
      margination and cooperation with resident sinusoidal cells require clarification.
      However, in vivo harvesting of portal blood leukocytes is associated with
      cumbersome cannulation of portal and hepatic veins and manipulation of the liver,
      causing major disturbances in splanchnic blood flow and liver blood supply,
      totally distorting sinusoidal blood perfusion and leukocyte margination. To
      overcome these difficulties, we have developed an in situ normothermic rat liver
      perfusion model permitting quantitative observations of blood leukocyte
      extraction in sinusoids. First, liver was flushed through the portal vein and the
      effluent leukocytes, named liver-associated leukocytes (LAL1), were collected
      from hepatic veins. Then, the liver was perfused for 60 min with 50 ml of blood
      using a semiclosed perfusion system. Upon completion of perfusion, the liver
      portal vasculature was flushed again to retrieve the leukocytes extracted from
      the perfusing blood (LAL2). These cells were characterized with respect to their
      phenotype and cytotoxicity. The mean leukocyte count of the washout before
      perfusion was 1.04+/-0.2x10(6)/g of liver tissue and 0.9+/-0.1x10(6)/g after 60
      min of perfusion, indicating retention by the perfused liver, the live leukocyte
      extracting capacity. To further evaluate the efficiency of perfusion, FITC
      labelled leukocytes were added to the perfusing leukocyte-free blood. Around 95%
      of the postperfusion washout LALs were FITC(+). Heat-killed leukocytes did not
      marginate in sinusoids. Preincubation of leukocytes with substances able to lower
      adhesion capacity, such as lidocaine, trypsin and AAGM1, significantly decreased
      the postperfusion LAL2 washout population. The numbers of extracted postperfusion
      LAL2 CD5(+), CD4(+), CD8(+), CD56(+) and class II(+) subsets did not differ
      statistically from those of preperfusion LAL1. Moreover, the cytotoxicity of LAL2
      and LAL1 against CC531 and K562 remained at a similar level. Thus, perfused liver
      also retained its selective leukocyte extraction capacity. This model shows that
      the process of selective margination of portal blood cell subsets in the liver
      can be studied in an artificially perfused liver subject to physiological blood
      flow parameters, temperature, oxygenation and minimal ischemic time before
      connection to the perfusion device. Furthermore, it is suitable for studies of
      the selective recruitment of blood cells in sinusoids in a wide large of
      situations including liver tumors, infections, rejection after transplantation,
      graft vs. host disease, as well as in the investigation of the effect of drugs on
      these processes.

PMID- 12505718
TI  - An in vitro cell model system for the study of the effects of ozone and other
      gaseous agents on phagocytic cells.
AB  - Ozone (O(3)), a major component of air pollution and a very strong oxidizing
      agent, can lead to lung injury associated with edema, inflammation, and
      epithelial cell damage. The ozone effects on pulmonary immune cells have been
      studied by various in vivo and in vitro systems. In this report, we characterized
      a model system of cells of monocyte/macrophage lineage (THP-1 cells) exposed to
      ozone in vitro by studying cell viability and cell surface marker expression. THP
      1 cells exposed to ozone in concentrations ranging from 0.1 to 0.5 ppm for 1 h
      were analyzed for cell viability and apoptosis (Annexin V/7-Amino-actinomycin D
      (7-AAD) flow cytometric assay) either immediately after ozone exposure or at
      later time points. This analysis showed absence of apoptosis and a small decrease
      in cell viability (5-17%) in ozone-exposed THP-1 cells. Cell surface protein
      expression (CD14 and CD11b) did not change following ozone exposure, but the
      effect of lipopolysaccharride (LPS) on TNF-alpha production following ozone
      exposure changed compared to filtered air/LPS-exposed cells. These findings
      indicate that this in vitro ozone cell-exposure system may be used in studies
      where the effects of various agents (physiological and non-physiological) on
      phagocytic cells can be analyzed. This model system offers conditions where the
      experimental results are not due to cell death, but rather due to the effects of
      ozone and/or agents under investigation.

PMID- 12505719
TI  - Use of co-immunoelectrodiffusion to detect presumed disease-associated
      precipitating antibodies, and time-course value of specific isotypes in bird
      breeder's disease.
AB  - BACKGROUND AND OBJECTIVE: The practical value of immunological diagnosis of bird
      breeder's disease (BBD) is controversial, because of difficulties in
      distinguishing active disease patients from simple contact subjects. The aim of
      this study was to determine the diagnostic and prognostic value of (a) presumed
      disease-associated antibodies precipitating pigeon antigens (immunoglobulin A
      (IgAp) and P2 component), (b) characterization of specific isotypes (IgG, IgM,
      and IgA), and (c) antibody kinetics after antigen eradication. METHODS: 405
      subjects (775 sera) in contact with birds were studied [by means of co
      immunoelectrodiffusion (Co-IED) and enzyme-linked immunofiltration (ELIFA)] with
      soluble extracts of pigeon droppings and squab crop milk. These patients were
      divided into two groups based on the final clinical evaluation of the patients'
      physicians, which was taken as the gold standard (positive in 90 and negative in
      315 cases). RESULTS: On the basis of this gold standard, the detection of
      presumed disease-associated precipitating antibodies by Co-IED had a specificity
      of 95.5%, a sensitivity of 98.7%, an accuracy of 98%, and positive and negative
      predictive values of 95.5% and 98.7%, respectively. Most of the patients with a
      final positive diagnosis of BBD had specific IgG, IgM, and IgA antibodies by
      ELIFA. After antigen eradication, anti IgAp and/or P2 antibodies disappeared more
      rapidly than other precipitating systems. CONCLUSION: Identification by Co-IED of
      precipitating immune complexes IgAp and/or P2 significantly reinforces the
      intrinsic credibility of immunological diagnosis of BBD. Compared to these
      presumed disease-associated precipitating antibodies, detection and time course
      of specific IgM, IgA antibodies, provided no additional diagnostic value or
      prognostic arguments to judge disease activity after antigen eradication.

PMID- 12505720
TI  - Detection and activation of human Valpha24+ natural killer T cells using alpha
      galactosyl ceramide-pulsed dendritic cells.
AB  - Human CD1d-restricted natural killer T (NKT) cells, which are postulated to
      regulate the immune response in several clinical settings, can be activated by
      alpha-galactosylceramide (alpha-GalCer) presented by CD1d molecules on antigen
      presenting cells (APCs). Simple methods to quantify NKT function in fresh blood
      will greatly benefit studies targeting NKT cells in humans. Here we show that
      freshly isolated human NKT cells can be readily quantified by an enzyme-linked
      immunospot (ELISPOT) assay and have a Th1 profile (secreting interferon-gamma,
      but not IL-4), after stimulation using alpha-GalCer loaded APCs. Using this
      assay, we also evaluated APC requirements for human NKT cell activation in fresh
      blood. Monocyte-derived dendritic cells (DCs) are more effective than
      monocytes/macrophages for detecting and activating NKT cells in fresh blood, with
      mature alpha-GalCer pulsed DCs being optimal. DCs are also efficient APCs for
      expanding NKT cells in culture and generating NKT cell lines. NKT cells expanded
      with DCs were functional, secreting both IFN-gamma and IL-4, and killing NKT
      sensitive targets. Optimal activation of these lines was seen using mature DCs
      loaded with 10-100 ng/ml of alpha-GalCer. DCs matured with several different
      stimuli were effective. These data help to establish the conditions for loading
      DCs with alpha-GalCer for immune therapeutic targeting of NKT cells, and provide
      a new simple assay to monitor NKT function in humans.

PMID- 12505721
TI  - Four different clones of mouse anti-acetyllysine monoclonal antibodies having
      different recognition properties share a common immunoglobulin framework
      structure.
AB  - By employing two different immunogens and two different antibody-screening
      strategies, we established four mouse hybridoma clones producing monoclonal
      antibodies against N epsilon -acetyllysine. Three different protocols were used
      in this study; i.e., mice were (1) immunized with an N epsilon -acetyllysine
      containing peptide, Gly-Lys(Ac)- epsilon -aminocaproic acid (Aca)-Cys, conjugated
      to KLH, and the hybridoma clones were screened for their reactivity to a histone
      H3 peptide containing five acetyllysines; (2) immunized as in "1" and screened
      with chemically acetylated bovine serum albumin (BSA); (3) immunized with
      chemically acetylated keyhole limpet hemocyanin (KLH) and screened with
      chemically acetylated BSA. Antibodies produced by the four different hybridomas
      established here all reacted with acetyllysine residues, but their reactivity was
      not the same when evaluated with enzyme-linked immunosorbent assay (ELISA),
      Western blotting, and resonant mirror sensor analyses. Among the three protocols
      examined, protocol "3" was especially useful to obtain hybridomas producing anti
      N epsilon -acetyllysine antibodies that could detect not only the acetylated
      histones but also other acetylated proteins. By cloning and sequencing the cDNAs
      encoding the variable regions of the antibodies, we found that their framework
      sequences were almost the same, which suggests that some framework amino acids in
      addition to their complementarity determining regions (CDRs) directly contribute
      to their recognition function.

PMID- 12505722
TI  - Identification of an antigen-specific B cell population.
AB  - The difficulty in characterizing antigen-specific B cells that arise in the
      native B cell repertoire has been a formidable obstacle to understanding both
      protective and pathogenic antibody responses. We have developed a tetramer-based
      technique for identifying antigen-specific B cells. Biotin-labeled antigen is
      made tetrameric by interaction with streptavidin. The enhanced avidity of this
      antigenic compound for the B cell membrane permits the visualization,
      characterization and isolation of antigen-specific B cells.

PMID- 12505723
TI  - A novel enhanced green fluorescent protein (EGFP)-K562 flow cytometric method for
      measuring natural killer (NK) cell cytotoxic activity.
AB  - Enhanced green fluorescent protein (EGFP) was stably expressed in human
      erythroleukaemia K562 cells (EGFP-K562) and used as target cells for measurement
      of natural killer (NK) cell cytotoxicity by flow cytometry. The compromised EGFP
      K562 target cells were stained with propidium iodide (PI) and showed dual (green
      red) fluorescent. Although the kinetic study demonstrated that the optimal
      incubation time for the assay was 4 h, a 2-h incubation period also gave
      comparable results. This new technique correlated strongly with the standard
      chromium (51Cr) release assay at the correlation coefficients of 0.87 and 0.89 at
      p-value <0.001 for 2- and 4-h incubation times, respectively. The EGFP-K562
      stable cell line provides a novel method to measure NK cytotoxicity by flow
      cytometry without pre-staining or pre-labeling target cells.

PMID- 12505724
TI  - Expression of recombinant proteins in a lipid A mutant of Escherichia coli BL21
      with a strongly reduced capacity to induce dendritic cell activation and
      maturation.
AB  - Mutations in the Escherichia coli (E. coli) and Salmonella lpxM gene have been
      shown to result in strains which grow normally and which produce a non
      myristoylated lipopolysaccharide (nmLPS) with strongly reduced endotoxicity.
      Using homologous recombination, we inactivated the lpxM gene in BL21 (DE3), a
      strain widely used for the production of recombinant proteins. This led to a
      derivative unaffected in its capacity to support the production of recombinant
      proteins. This new strain expresses non-myristoylated LPS that induces markedly
      less activation and maturation of monocyte-derived dendritic cells (DC), as
      assessed by nuclear translocation of nuclear factor kappa B (NF-kappaB),
      production of TNF-alpha and IL-8 or expression of CD86. Activation of the main
      signal transducing receptor for extracellular LPS, Toll like receptor (TLR) 4 in
      conjunction with the soluble accessory protein MD-2 was also markedly decreased.
      The modified BL21 strain represents a new application of lpxM inactivation for
      the expression of proteins to be tested on dendritic cells or other LPS sensitive
      cells/receptor complexes. It is likely to be useful for the identification of new
      proteins activating the innate immune response and to reducing the risk linked
      with low level of endotoxin contamination in therapeutic recombinant proteins.

PMID- 12505725
TI  - A highly sensitive quantitative immunochromatography assay for antigen-specific
      IgE.
AB  - We have developed a highly sensitive quantitative enzyme immunochromatography
      system for antigen-specific IgE, which is clinically important for the diagnosis
      of allergic diseases. The system uses alkaline phosphatase-labeled anti-IgE
      antibody (ALP-anti-IgE) and immobilized target antigen, for example cedar pollen
      antigen, on a membrane. Antigen-specific IgE present in the serum binds the
      immobilized antigen after complexing with the ALP-anti-IgE. Subsequently, the
      enzyme substrate migrates to the complex on the antigen line, which is stained
      blue. The intensity of the staining was analyzed by a quantitative detector, but
      can also be assessed directly by the naked eye. This system was able to detect
      0.2 U/ml of IgE specific for Japanese cedar pollen. The results correlated well
      (Spearman's rank correlation coefficient, 0.95) to those in AlaSTAT system, which
      is a reliable enzyme-linked immunosorbent assay (ELISA) method. This antigen
      specific IgE assay system is suitable for point-of-care testing.

PMID- 12505726
TI  - Colony lift assay using cell-coated filters: a fast and efficient method to
      screen phage libraries for cell-binding clones.
AB  - For efficient screening of phage antibody libraries obtained by selection on
      whole cells, we have developed a modified colony lift assay using cell-coated
      filters. Both cells growing in suspension as well as adherent cells can be coated
      onto nitrocellulose filters and used to detect bacterial colonies responsible for
      the production of cell-binding (specific) single chain variable fragment (scFv)
      antibodies. We demonstrate, using a selected library developed in our laboratory
      (named "AB" library) as a model system, that the frequency of specific clones as
      detected by colony lift assay using cell-coated filter is comparable to the
      frequency of positive clones as detected by the "classical" method (i.e. random
      picking and flow cytometric analysis). However, the colony lift assay enables
      detection and isolation of a higher number of specific clones as compared to the
      random pick. This is due to screening of a much higher number of clones
      simultaneously (it is possible to screen at least 1000 clones plated on one 9-cm
      agar dish). Using this method, clones occurring at a low frequency (such as
      present in early selection rounds) can be detected and isolated efficiently. We
      clearly demonstrate the usefulness of the colony lift assay with cell-coated
      filter by applying it to screen the head-and-neck carcinoma (HN) library (a
      selected library generated in our laboratory). Using the assay, but not the
      random picking, we were able to isolate specific clones from 2nd to 3rd selection
      rounds of the HN library.

PMID- 12505727
TI  - A yeast display system for engineering functional peptide-MHC complexes.
AB  - In a cellular immune response, antigenic peptides derived by intracellular
      processing of foreign pathogens are bound to the class I major histocompatability
      complex (MHC I) and presented to CD8(+) cytotoxic T cells. Although the crystal
      structures of several different MHC products have been solved, many MHC
      molecules, including some associated with diseases, have not been amenable to
      biochemical and structural studies. The variability in this success is based
      largely on the fact that peptide-MHC complexes vary extensively in their
      stability. These properties also are intimately tied to the biological activity
      of the complexes. The ability to apply the techniques of directed evolution to
      this system in order to engineer stable complexes has been complicated by the
      trimeric structure of peptide-MHC complexes, requiring association of three
      polypeptides: the heavy chain, beta2-microglubulin (beta2m), and a short peptide.
      We show here that single-chain forms of peptide-MHC complexes can be expressed as
      Aga-2 fusions on the surface of yeast. Three different complexes, SIYRYYGL-K(b)
      beta2m (SIYR-K(b)), EQYKFYSV-K(b)-beta2m (dEV8-K(b)), and SIINFEKL-K(b)-beta2m
      (OVA-K(b)), were expressed on yeast and detected by flow cytometry with a
      conformation-specific anti-K(b) antibody (B.8.24.3). In addition, yeast
      displaying K(b) loaded with exogenous SIYR and OVA peptides were recognized by a
      high-affinity T cell receptor that is specific for SIYR-K(b) and by an antibody
      (25.D1-16) that is specific for OVA-K(b), respectively. Finally, yeast that
      display the SIYRYYGL-K(b) also directly stimulated CD69 up-regulation on naive 2C
      T cells. Hence, yeast display represents a technology that can be used for
      directed evolution of any of the components of the trimeric pep-MHC complex.

PMID- 12505728
TI  - A sensitive time-resolved fluorescent immunoassay for metallothionein protein.
AB  - Metallothioneins (MTs) are a family of low molecular weight metal-binding
      proteins induced by a broad range of stress conditions, including exposure to
      transition metal ions. Biochemical and immunological methods to measure MT
      protein levels in tissues and cultured cells have been reported, but accuracy and
      sensitivity is impeded by high background levels, low specificity of currently
      available reagents, and relatively laborious and time-consuming multistep
      procedures. To address these difficulties, a protocol has been developed to
      measure MT protein levels using a competitive solid phase assay based on
      dissociation enhanced lanthanide fluoroimmuno (DELFIA) detection of anti-MT
      monoclonal antibody bound to solid phase MT. This assay allows time-resolved
      detection of antibody binding, based on binding and exchange of different
      lanthanide chelates followed by fluorescent detection, designed to reduce
      background fluorescence and increase sensitivity. The method allows measurement
      of low MT levels that are undetectable using current radioimmunoassay (RIA) and
      enzyme-linked immunosorbent assay (ELISA) protocols, and yields reproducible
      results with low background over a wide range of MT concentrations. Improved
      sensitivity of MT protein detection is of value in toxicological measurement of
      stress responses and assessment of MT expression and function.

PMID- 12505729
TI  - Modeling individual variation in biomarker response to combination
      immunosuppression with stimulated lymphocyte responses-potential clinical
      implications.
AB  - BACKGROUND: In mitogen-stimulated lymphocyte responses (sLR), cytokines and cell
      surface receptors in peripheral human blood lymphocytes (PBL) are sensitive to
      cyclosporine (CsA), and can predict its in vivo effect with pharmacodynamic (PD)
      modeling. This is not known for multiple-agent combinations. METHODS: Twenty-five
      concentration mixtures of CsA (0-1200 ng/ml) plus sirolimus (SRL, 0-30 ng/ml)
      were added to whole blood from five normal human subjects (NHS) for effect on a
      limited array of six targets. Effect-concentration relationships were analyzed
      with E(max) PD equations, and expressed as the range of concentration mixtures
      associated with one-half of maximal inhibitory effect (EC(50)) on a model
      biomarker target. This predicted range was examined to see whether it contained
      representative concentration mixtures of these two drugs, which were associated
      with a stable post-transplant outcome in a logistic regression model of 1039
      clinical trial patients. RESULTS: PD analyses suggested that in NHS samples
      containing CsA+SRL (n=5), (1) PMA-Ionomycin-stimulated T-cell expression of
      intracellular IL-2, TNF-alpha, and IFN-gamma was inhibited by CsA, and minimally
      by SRL, and (2) the two agents inhibited pokeweed mitogen (PWM)-stimulated B-cell
      expression of CD54 and CD95, but not CD86 (ICAM-1, Fas antigen, and B7.2),
      synergistically. With CD54 as the model biomarker, contour plots also predicted a
      wide range of concentration mixtures of the two agents across which an EC(50)
      could be predicted for CsA+SRL in a population (e.g., CsA-72 ng/ml+SRL 15 ng/ml,
      n=5), as well as in the individual subject (e.g., CsA-0 ng/ml+SRL-13.75 ng/ml in
      NHS-D310). Logistic regression analysis of clinical outcomes in 1039 patients
      suggested that the concentration mixture of CsA congruent with 50-150 ng/ml+SRL
      congruent with 10 ng/ml was associated with a stable post-transplant course. The
      EC(50) contour plot for CD54 suggested a nearly identical CsA concentration of
      120 ng/ml in the presence of 10 ng/ml of sirolimus. CONCLUSIONS: Our data suggest
      that pharmacodynamic evaluation of immunosuppressive agents with biomarkers may
      be an efficient process with which to characterize immunosuppressive effect of
      combination agents in individual patients and in patient populations.

PMID- 12505731
TI  - The Resuscitation Greats: Andreas Vesalius, the concept of an artificial airway.

PMID- 12505732
TI  - Induced hypothermia using large volume, ice-cold intravenous fluid in comatose
      survivors of out-of-hospital cardiac arrest: a preliminary report.
AB  - STUDY HYPOTHESIS: Recent studies have shown that induced hypothermia for twelve
      to twenty four hours improves outcome in patients who are resuscitated from out
      of-hospital cardiac arrest. These studies used surface cooling, but this
      technique provided for relatively slow decreases in core temperature. Results
      from animal models suggest that further improvements in outcome may be possible
      if hypothermia is induced earlier after resuscitation from cardiac arrest. We
      hypothesized that a rapid infusion of large volume (30 ml/kg), ice-cold (4
      degrees C) intravenous fluid would be a safe, rapid and inexpensive technique to
      induce mild hypothermia in comatose survivors of out-of-hospital cardiac arrest.
      METHODS: We enrolled 22 patients who were comatose following resuscitation from
      out-of-hospital cardiac arrest. After initial evaluation in the Emergency
      Department (ED), a large volume (30 ml/kg) of ice-cold (4 degrees C) lactated
      Ringers solution was infused intravenously over 30 min. Data on vital signs,
      arterial blood gas, electrolyte and hematological was collected immediately
      before and after the infusion. RESULTS: The rapid infusion of large volume, ice
      cold crystalloid fluid resulted in a significant decrease in median core
      temperature from 35.5 to 33.8 degrees C. There were also significant improvements
      in mean arterial blood pressure, renal function and acid-base analysis. No
      patient developed pulmonary odema. CONCLUSION: A rapid infusion of large volume,
      ice-cold crystalloid fluid is an inexpensive and effective method of inducing
      mild hypothermia in comatose survivors of out-of-hospital cardiac arrest, and is
      associated with beneficial haemodynamic, renal and acid-base effects. Further
      studies of this technique are warranted.

PMID- 12505733
TI  - Is the orientation of the apical defibrillation paddle of importance during
      manual external defibrillation?
AB  - OBJECTIVE: Transthoracic impedance (TTI) is a factor determining the magnitude of
      the transmyocardial current during external defibrillation. Minimising TTI
      increases the chances of successful defibrillation. Most external defibrillation
      paddles are rectangular in shape and can, therefore, be placed in a transverse or
      longitudinal orientation. The apical paddle is often placed in a transverse
      orientation. This may theoretically result in a higher TTI than a longitudinal
      orientation because of poorer contact at the lateral paddle edges. We compared
      TTI with the apical paddle in both a transverse and longitudinal orientation.
      MATERIALS AND METHODS: Twenty sequential anaesthetised patients were studied. A
      pair of defibrillator paddles were instrumented to measure paddle force. TTI was
      recorded pre-operatively at end-expiration with the apical paddle in both
      longitudinal and transverse orientations. The sternal paddle was placed in a
      longitudinal orientation for all measurements. RESULTS: TTI decreased in both
      transverse and longitudinal orientations as paddle force increased. Transverse
      paddle orientation resulted in a significantly (P<0.01) higher TTI than
      longitudinal orientation at all paddle forces below 12 kg force. CONCLUSION: The
      longitudinal orientation of a rectangular defibrillation paddle provides a lower
      TTI than orientation horizontally.

PMID- 12505734
TI  - How do you size a nasopharyngeal airway.
AB  - OBJECTIVE: To measure an appropriately sized nasopharyngeal airway, it is taught
      that the size is related to the patients little finger or nostril (anterior
      nares). This study has been designed to identify whether these comparisons are
      valid. METHOD: Direct comparison of the dimensions of ten subjects' little
      fingers and anterior nares with the internal anatomy of their nose as visualised
      on coronal MRI scans. RESULTS: Neither method correlated statistically with the
      nasal anatomy of that subject. CONCLUSIONS: The methods used traditionally to
      size a nasopharyngeal airway do not correlate with the airway anatomy and are
      unreliable. It is more appropriate to size the airway dependent upon the
      patient's size, sex and race.

PMID- 12505735
TI  - Interaction between emergency medical dispatcher and caller in suspected out-of
      hospital cardiac arrest calls with focus on agonal breathing. A review of 100
      tape recordings of true cardiac arrest cases.
AB  - AIM: One of the objectives of this study was to assess the emergency medical
      dispatchers (EMDs) ability for the identification and prioritisation of cardiac
      arrest (CA) cases, and offering and achievements of dispatcher-assisted bystander
      cardiopulmonary resuscitation (CPR). The other objective was to give an account
      of the frequency of agonal respiration in cardiac arrest calls and the caller's
      descriptions of breathing. METHODS: Prospective study evaluating 100 tape
      recordings of the EMD calls of emergency medical service (EMS)-provided advanced
      life support- (ALS) cases, of out-of-hospital cardiac arrest. RESULTS: The
      quality of EMD-performed interviews was highly commended in 63% of cases, but
      insufficient or unapproved in the remaining 37%. The caller's state of mind was
      not a major problem for co-operation. Among the 100 cases, 24 were suspected to
      be unconscious and in respiratory arrest. A further 38 cases were presented as
      unconscious with abnormal breathing. In only 14 cases dispatcher-assisted
      bystander CPR was offered by the EMD, and in 11 of these it was attempted, and
      completed in eight. Only four of the cases were unconscious patients with
      abnormal breathing. The incidence of suspected agonal breathing was estimated to
      be approximately 30% and the descriptions were; difficulty, poorly, gasping,
      wheezing, impaired, occasional breathing. CONCLUSIONS: Among suspected cardiac
      arrest cases, EMDs offer CPR instruction to only a small fraction of callers. A
      major obstacle was the presentation of agonal breathing. Patients with a
      combination of unconsciousness and agonal breathing should be offered dispatcher
      assisted CPR instruction. This might improve survival in out-of hospital cardiac
      arrest.

PMID- 12505736
TI  - Measurement of end-tidal carbon dioxide in spontaneously breathing patients in
      the pre-hospital setting. A prospective evaluation of 350 patients.
AB  - OBJECTIVE: Monitoring of end-tidal carbon dioxide (EtCO(2)) is good clinical
      practice in the patient who is intubated and ventilated. This study investigated
      the EtCO(2) values in spontaneously breathing patients treated in a physician
      staffed mobile intensive care unit (MICU). This article also discusses whether
      EtCO(2) monitoring may have an influence on therapeutic decisions by emergency
      physicians by providing additional information. METHODS: Over a period of 6
      months, 350 spontaneously breathing patients (162 males, 137 females) were
      treated and transported in our MICU and monitored using a LifePak 12 monitor
      (EtCO(2), respiratory rate, pO(2), blood pressure, heart rate). Only 299 were
      enrolled in the study. RESULTS: Pathological EtCO(2) values were detected in 19
      patients (6.3%). EtCO(2) levels of >55 mmHg (7.3 kPa) were found in nine of 12
      (75%) patients with asthma, in one of 23 patients with hypoglycaemia (4.3%), and
      in all patients with subarachnoid hemorrhage, acute seizures and drug
      intoxications. With the exception of the asthma patients, all patients had an
      initial Glasgow Coma Score <8. EtCO(2) levels <20 mmHg (2.7 kPa) were found in
      all patients with hyperventilation or shock due to volume deficiency. Errors in
      EtCO(2) measurement occurred in 5% of cases. CONCLUSION: Although EtCO(2)
      monitoring may be a useful additional variable in spontaneously breathing
      patients. Consideration of the respective disease and the cost to benefit ratio
      suggests that this method should only be used for selected indications.

PMID- 12505737
TI  - A survey of the in-hospital response to cardiac arrest on general wards in the
      hospitals of Rome.
AB  - OBJECTIVE: To investigate the response to cardiac arrest in general wards.
      METHODS: Direct interview with the cardiac arrest team (CAT) members in 32
      hospitals in Rome, Italy. RESULTS: The majority of CATs are activated by
      telephone but only two (6%) hospitals have a dedicated telephone number for
      emergency calls. The CAT always includes a physician, who is usually an
      anaesthesiologist (30 hospitals, 94%), and usually includes one or two other
      members (23 hospitals, 72%). In 21 hospitals (65%) there is less than one
      defibrillator per floor but in only six hospitals (19%), CATs are equipped with
      defibrillators. Resuscitation guidelines are adopted by 15 teams (47%). The
      Utstein style of data collection is used in only one hospital. The most common
      problems reported by the CATs are: insufficient training of ward personnel (29
      hospitals, 91%), insufficient staff (19 hospitals, 59%) and insufficient
      equipment (18 hospitals, 56%). Average maximum arrival time for the CAT to arrive
      is 220 s, but varies significantly between single-building and the multiple
      building hospitals (88 vs. 390 s; P<0.001). CONCLUSIONS: The majority of the
      cardiac arrest teams have acceptable response times, but their efficiency may be
      impaired by the lack of staff, equipment and co-ordination with the ward
      personnel. CAT members identified a strong need for BLS training of ward
      personnel. More widespread introduction of standard protocols for resuscitation
      and reporting of cardiac arrest are necessary to evaluate aspects that may need
      improvement.

PMID- 12505738
TI  - Aspiration pneumonia following severe self-poisoning.
AB  - PURPOSE: To investigate the risk factors of aspiration pneumonia following severe
      self-poisoning. MATERIALS AND METHODS: Patients treated due to severe self
      poisoning in the ICU of Oulu University Hospital, Oulu, Finland during 1.11.1989
      31.10.2000 were analyzed retrospectively. RESULTS: 28.4% of 257 patients
      fulfilled the criteria of aspiration pneumonia. An unconscious patient who was
      not intubated until arrival at the emergency room (ER) had an odds ratio (OR) of
      3.34 (CI 1.3-8.7) for aspiration pneumonia. If the patient was intubated at the
      first contact with health care providers, OR was 1.8 (CI 0.6-5.7). The use of
      gastric lavage or activated charcoal in the case of a non-intubated unconscious
      patient led to ORs of 2.7 (CI 0.8-9.3) and 3.7 (CI 1.01-12.5), respectively. The
      mean length of ICU stay was 0.9 (CI 0.8-0.9) days among patients without
      aspiration pneumonia and 1.9 (CI 1.3-2.6) days among those with aspiration
      pneumonia. The mean length of hospital stay was 2.8 (CI 2.5-3.1) days among the
      patients without aspiration pneumonia and 6.5 (CI 5.3-7.6) days among those with
      aspiration pneumonia. CONCLUSION: To avoid aspiration pneumonia intubation of an
      unconscious patient on scene before arrival at the ER is recommended. The use of
      gastric lavage and activated charcoal increase the risk of aspiration pneumonia
      if the patient is unconscious and not intubated. Aspiration pneumonia
      significantly prolongs the length of ICU and hospital stay.

PMID- 12505739
TI  - Opportunities to prevent sudden out-of-hospital death due to coronary heart
      disease in a community.
AB  - BACKGROUND: Intervening successfully to reduce the burden of sudden out-of
      hospital death due to coronary heart disease (OHCD) requires knowledge of where
      these deaths occur and whether they are observed by bystanders. METHODS: To
      establish the proportion of OHCDs that were witnessed and where they occurred, we
      reviewed the coroner's notes and medical records of a previously-described sample
      of OHCD cases among residents of Olmsted County, Minnesota. This cohort (n=113)
      consisted of a 10% random sample of all Olmsted County residents who died out-of
      hospital between 1981 and 1994 and whose deaths were attributed to coronary heart
      disease. RESULTS: Excluding deaths in nursing homes (n=27), 71 (83%) of the
      deaths occurred in private homes and 15 (17%) occurred in public places. The
      event was not witnessed in 59% of deaths occurring in private homes and in 20% of
      deaths occurring in public places. The presence or absence of a bystander could
      not be established for 10% of deaths in private homes and 7% of deaths in public
      areas. CONCLUSIONS: A significant proportion of OHCDs occur in private homes and
      are not witnessed. Prevention of unwitnessed deaths will require programs that
      result in primary prevention and/or calls to first responders at the time of
      impending cardiac arrest.

PMID- 12505740
TI  - Utstein style analysis of rural out-of-hospital cardiac arrest [OOHCA]: total
      cardiopulmonary resuscitation (CPR) time inversely correlates with hospital
      discharge rate.
AB  - OBJECTIVE: Survival after out-of-hospital cardiac arrest (OOHCA) in an urban
      environment is directly proportional to speed of defibrillation and effective
      bystander cardiopulmonary resuscitation (CPR). We hypothesized that the hospital
      discharge rate from rural OOHCA was affected by the same factors. METHODS: We
      studied all OOHCAs in 1998 for rural Alachua County, Florida, with one emergency
      medical system (EMS) transport provider and three hospitals. All EMS identified
      OOHCA were reviewed retrospectively, as were EMS and hospital records. The 1998
      County population was 211403; 1495 deaths from all causes occurred (70.7/10(4)
      pop). Of 167 OOHCAs (7.9/10(4) pop), 145 were of cardiac etiology; 22 were
      excluded (13 scene deaths, four traumatic, one intraoperative and three
      respiratory arrests, one arrest during a hospital-to-hospital transfer) and in
      eight outcome data were not available in any form. A total of 137/145 (94.5%)
      OOHCA patients had analyzable data. Data were analyzed using Student's t-test and
      ANOVA. Alpha was set at 0.05. RESULTS: Of 25 patients (18.2% of OOHCA) with
      restoration of spontaneous circulation (ROSC), six survived (4.4% of total, 24%
      of those with ROSC) to discharge from hospital (four to a skilled nursing
      facility, one each home with and without assistance). Four patients were still
      alive at >or=1 year post arrest. Asystole as the initial rhythm (P=0.014), and
      emergency department (ED) CPR time (8 vs. 15.5 min, P=0.042 for survivors vs. non
      survivors) were the only factors statistically affecting survival. While
      bystander CPR was not significantly different between groups, there was a
      significantly higher proportion of patients surviving in the ED who had ROSC, and
      a higher proportion who had ROSC after bystander CPR. Time to defibrillation in
      nonsurvivors, while not statistically different between city and county patient
      groups, was clinically different. Statistical significance would likely have been
      achieved with a larger study population. CONCLUSION: Our data suggest improvement
      in response time and bystander CPR might further improve survival in a rural
      setting.

PMID- 12505741
TI  - Factors influencing Queenslanders' willingness to perform bystander
      cardiopulmonary resuscitation.
AB  - STUDY OBJECTIVE: The chances of surviving an out-of-hospital cardiac arrest
      (OHCA) are greatly increased if a bystander provides cardiopulmonary
      resuscitation (CPR) while awaiting the arrival of the emergency medical services.
      Over 50% of adult Queenslanders have been trained in CPR at some time in the
      past, however, little is known about the factors that affect their willingness to
      perform CPR. METHOD: A random survey of 4480 Queensland residents was conducted
      to address this question. RESULTS: The survey indicated that the most common
      barriers to performing CPR were a fear of disease, visible blood and perceived
      danger. In contrast, respondents indicated that they were more likely to
      administer CPR if the respondent knew the victim, the victim would die if CPR was
      not administered, and respondents believed that they possessed the necessary
      skills to perform CPR. A majority (84%) of respondents indicated that they were
      at least likely to administer CPR. A logistic regression analysis revealed that
      the respondents most likely to perform CPR were males, those who were married or
      in a de facto relationship, those in paid employment, smokers, those recently
      trained in CPR, prospective organ donors, those who cited no barriers to CPR and
      those who cited one or more factors that would facilitate CPR. CONCLUSIONS: This
      study indicates that there is considerable variation in Queenslanders'
      willingness to perform bystander CPR. Public health education campaigns aimed at
      correcting inaccurate perceptions of risk and addressing other barriers to
      bystander CPR would promote its use in response to OHCA.

PMID- 12505742
TI  - The acquisition and maintenance of defibrillation skills by lay first responders.
AB  - OBJECTIVE: Non-traditional and lay first responders increasingly are being
      trained in the skill of defibrillation. With simplification of new devices, there
      is a need to determine optimal first responder selection and training and
      maintenance of this important skill. These issues are of prime importance for the
      St John Ambulance Australia Operations Branch which already has a substantial
      first response defibrillation programme. DESIGN: We trained 12 trainers (3 h and
      30 min), who subsequently instructed 41 further first responders (2 h and 30
      min), a total group with a broad range of pre-existing experience and skill
      level, in the use of an automated external defibrillator (AED). Acquisition and
      maintenance of the AED skill was determined by four criteria at three monthly
      intervals. RESULTS: St John first responders with higher qualification levels
      were more likely to acquire the skill of defibrillation successfully (r=0.37,
      P<0.05). However, once acquired, the skill was easily maintained by virtually all
      (98%) members. A positive correlation was noted between the overall score
      achieved at the 6-month re-assessment and the number of times members had taken
      an AED 'on duty' (r=0.31, P<0.05). CONCLUSION: For St John first responders
      proficient in cardiopulmonary resuscitation (CPR), the skill of defibrillation
      with an AED is readily acquired and maintained. While less experienced members
      may be less likely to acquire the skill initially, once acquired the skill is
      equally maintained by all, provided ongoing 'on duty' exposure is available.

PMID- 12505743
TI  - Rescuer position for tracheal intubation on the ground.
AB  - BACKGROUND: Emergency oral tracheal intubations in the pre-hospital setting can
      be more difficult because the rescuer's position with respect to a patient lying
      on the ground may not provide optimal conditions for intubation. Since optimal
      visualisation of the larynx often depends on the force generated during
      laryngoscopy, we measured the pressure required for intubation (P(i)) as well as
      the maximum pressure (P(max)) that can be generated with the laryngoscopy blade
      in seven intubator positions. METHODS: Nineteen hospital personnel with
      intubation experience participated in this study. A modified #3 Macintosh
      laryngoscope blade was used to measure the pressure exerted on the tongue of a
      manikin placed on the ground during intubation. The following positions were
      studied: standard, sitting, prone, kneeling, left and right lateral decubitus and
      straddling. RESULTS: Intubating in the straddling position required the lowest
      P(i), as a percent of P(max) (68+/-14%). This was significantly less than the
      prone, right lateral decubitus and sitting positions. (Tukey's W procedure,
      P<0.05) CONCLUSION: The straddling position affords the intubator significantly
      more reserve force than the prone, right lateral decubitus or sitting position.
      We suggest that the straddling position may be an advantageous position for pre
      hospital intubations especially when visualisation of the glottis is difficult.

PMID- 12505744
TI  - Transthoracic impedance does not decrease with rapidly repeated countershocks in
      a swine cardiac arrest model.
AB  - STUDY PURPOSE: Successful defibrillation is dependent upon the delivery of
      adequate electrical current to the myocardium. One of the major determinant of
      current flow is transthoracic impedance. Prior work has suggested that impedance
      falls with repeated shocks during sinus rhythm. The purpose of this study was to
      evaluate changes in transthoracic impedance with repeated defibrillation shocks
      in an animal model of cardiac arrest due to ventricular fibrillation (VF).
      METHODS: VF was electrically induced in anesthetized swine. After 5 min of
      untreated VF, monophasic or biphasic waveform defibrillation was attempted using
      a standard sequence of 'stacked shocks' (200, 300, then 360 J, if necessary)
      administered via adhesive electrodes. If one of the first three shocks failed to
      convert VF, conventional CPR was initiated and defibrillation (360 J) attempted 1
      min later. Strength-duration curves for delivered voltage and current were
      measured during each shock and transthoracic impedance calculated. Animals
      requiring a minimum of four shocks were selected for study inclusion. Impedance
      data from sequential shocks were analyzed using mixed linear models to account
      for the repeated-measures design and the variability of the initial impedance of
      individual animals. RESULTS: Thirteen animals (monophasic waveform, n=7, biphasic
      waveform, n=6) required at least four shocks to terminate VF (range 4-6).
      Transthoracic impedance did not change from the first shock in the 13 animals
      (46+/-8 Omega) to the fourth shock (46+/-9 Omega). In animals receiving more than
      four shocks, transthoracic impedance likewise did not change significantly from
      the first to the last shock, which terminated VF. The lack of a significant
      change in impedance was also observed when animals were analyzed according to
      defibrillation waveform. CONCLUSION: Transthoracic impedance does not change
      significantly with repeated shocks in a VF cardiac arrest model. This is likely
      due to the lack of reactive skin and soft tissue hyperemia and edema observed in
      non-arrest models.

PMID- 12505745
TI  - Whole body oxygen consumption and critical oxygen delivery in response to
      prolonged and severe carbon monoxide poisoning.
AB  - BACKGROUND: Carbon monoxide (CO) poisoning remains the leading cause of death by
      poisoning in the world. One of the major proposed mechanisms for CO toxicity is
      the binding of CO to cytochrome oxidase and interference with cellular oxygen
      utilization but evidence for this is inconclusive. AIM OF STUDY: This study
      examined the effects of prolonged CO exposure on the dynamics of whole body
      oxygen consumption (VO(2)) and oxygen delivery (DO(2)) in an attempt to observe
      if CO exposure results in a defect of oxygen utilization defect as determined by
      a reduction in VO(2) during the course of poisoning prior to reaching the point
      where VO(2) is directly dependent on DO(2). This critical level of DO(2)
      (DO(2)crit) produced by CO poisoning was compared to historical values produced
      by other insults, which decrease global body DO(2). METHODS: Five small dogs were
      ventilated for 2 h with 0.25% CO and room air followed by 0.5% CO until death.
      Cardiac index (Q), DO(2), VO(2), oxygen extraction ratio (OER), and systemic
      lactate were measured every 15 min until death. RESULTS: Carboxyhemoglobin (COHb)
      levels increased linearly over 2.5 h to values above 80% until death. VO(2)
      remained constant and not significantly different from baseline below a COHb of
      80%. At COHb levels above 80%, VO(2) precipitously dropped. Similarly lactate
      levels were not significantly elevated from baseline until VO(2) dropped. DO(2)
      decreased by 78% (from 23+/-6 ml/kg/min to 5+/-4 ml/kg/min) over time despite an
      increase in Q by 58% until levels of COHb were above 80%. OER increased from 19+/
      5% to 50+/-11% until death. The calculated DO(2)crit was 10.7+/-4 ml/min/kg,
      which is not significantly different from values ranging from 7 to 13 ml/min/kg
      reported in the literature due to other insults, which reduce DO(2). CONCLUSION:
      In this canine model of prolonged CO exposure, no gradual reduction in VO(2) or
      increase in systemic lactate prior to reaching DO(2)crit was noted. In addition,
      CO exposure does not appear to change the DO(2)crit. The combination of these
      findings does not support the theory that CO produces a whole body intracellular
      defect in oxygen utilization.

PMID- 12505746
TI  - The potential value of the protein S-100B level as a criterion for hyperbaric
      oxygen treatment and prognostic marker in carbon monoxide poisoned patients.
AB  - Carbon monoxide (CO) poisoning resulting in diffuse tissue hypoxia. Cerebral
      hypoxia is a major cause of morbidity and mortality after CO poisoning. There are
      some clinical criteria that could help a physician to make a decision concerning
      the application of hyperbaric oxygenation therapy. However, it would be
      convenient to discover an objective biochemical serum marker that could help in
      the grade evaluation of CO poisoning and indication of therapy in CO-poisoned
      patients. We present two case reports where the established criteria for the CO
      poisoning were not optimum for the decision regarding therapy. It seems that the
      S-100B protein could be used as a biochemical marker of CO induced brain injury.
      S-100B values could perhaps help us to select patients for hyperbaric oxygen
      therapy and to predict the short and long term outcome.

PMID- 12505747
TI  - Pulmonary air embolism in severe head injury.
AB  - Entry of air into the venous system leading to intracardiac air and pulmonary air
      embolism (PAE) has been reported in various clinical settings such as
      neurosurgical interventions in the sitting position and in autopsies on patients
      with head and neck injuries. We report the case of a 29-year-old male who
      developed severe pulmonary dysfunction after severe head injury in a high
      velocity car accident. Chest X-ray showed bilateral diffuse patchy infiltrates.
      Pneumothorax, haemothorax, pulmonary aspiration, various forms of pulmonary
      oedema and pulmonary contusion could be excluded. Furthermore, there was an open
      laceration of the frontal sinus and maxillo-facial fractures. The history of
      spontaneous respiration in sitting position at the scene, rapid improvement of
      pulmonary function within 30 h, small amounts of air in the brain parenchyma, and
      circulatory shock despite elevated central venous pressure in the initial phase
      led to the diagnosis of PAE as the primary cause of pulmonary dysfunction. The
      diagnostic approach and basic therapeutical principles in patients with PAE are
      described. In conclusion, the case presented emphasizes the importance of
      considering PAE as a possible cause of respiratory failure in patients with
      severe head injury.

PMID- 12505748
TI  - Polymorphisms of the vascular endothelial growth factor and susceptibility to
      diabetic microvascular complications in patients with type 1 diabetes mellitus.
AB  - There is increasing evidence implicating genetic factors in the susceptibility to
      diabetic microvascular complications. Recent studies suggest that increased
      expression of the cytokine vascular endothelial growth factor (VEGF) may play a
      role in the pathogenesis of diabetic complications. A number of polymorphisms in
      the promoter region of the VEGF gene have been identified. The aim was to
      investigate whether an 18 base pair (bp) deletion (D)/insertion (I) polymorphism
      at position -2549 in the promoter region of the VEGF gene is associated with the
      susceptibility to diabetic microvascular complications. Two hundred and thirty
      two patients with type 1 diabetes mellitus (T1DM) and 141 normal healthy controls
      were studied. The D/D genotype was significantly increased in those patients with
      nephropathy (n=102) compared to those with no complications after 20 years
      duration of diabetes (uncomplicated, n=66) (40.2% vs. 22.7%, respectively,
      chi(2)=5.5, P<.05). The combination of polymorphisms of VEGF together with the
      aldose reductase (ALR2) gene showed that in the nephropaths, 8 of the 83 subjects
      had the VEGF I allele together with the Z+2 5'ALR2 allele compared with 27 of the
      62 uncomplicated patients (chi(2)=26.7, P<.00001). The functional role of the D/I
      polymorphism was examined by cloning the region into a luciferase reporter assay
      system and transient transfection into HepG2 cells. The construct containing the
      18 bp deletion had a 1.95-fold increase in transcriptional activity compared with
      its counterpart that had the insert (P<.01). These results suggest that
      polymorphisms in the promoter region of the VEGF gene together with the ALR2 may
      be associated with the pathogenesis of diabetic nephropathy.

PMID- 12505749
TI  - Parameters of oxidative stress in children with Type 1 diabetes mellitus and
      their relatives.
AB  - Oxidative stress (OS) plays an important role in the pathogenesis of Type 1
      diabetes mellitus (DM). The aim of the study was to compare OS parameters in
      diabetic children and their first-degree relatives. Fifty diabetic children from
      the West Bohemian Region were examined as well as their 32 siblings (12 Boys and
      20 girls) and 65 of their parents during a period of 6 months. Thirty healthy sex
      and age-matched children studied before planned surgeries were normal controls
      for children, 40 healthy adult volunteers were controls for parents. OS
      parameters were evaluated in all participants of the study (superoxide dismutase,
      SOD; glutathione peroxidase, GSHPx; plasma antioxidant capacity, AOC; reduced
      glutathione, GSH; and malondialdehyde, MDA) and also Type 1 DM-associated
      antibodies (ICA and GADA). The results in diabetic children showed significantly
      lower GSHPx and AOC and increased MDA when compared with healthy children.
      Similar findings were found in their siblings but without statistical
      significance. It is consequently evident that decreased antioxidative protection
      and simultaneous free radical (FR) overproduction occur in diabetic children and
      that there is a similar, but not significant, tendency in their siblings. The
      findings warrant reducing OS in diabetic children and postponing disease onset in
      susceptible relatives.

PMID- 12505750
TI  - Association of monocyte chemoattractant protein-1 with renal tubular damage in
      diabetic nephropathy.
AB  - Monocyte chemoattractant protein-1 (MCP-1), is a chemokine that mediates renal
      interstitial inflammation, tubular atrophy, and interstitial fibrosis by
      recruiting monocytes/macrophages into renal tubulointerstitium. Recent studies
      have demonstrated that protein overload in renal tubular cells up-regulates MCP-1
      gene and its protein expression. Therefore, we hypothesized that increased
      expression of MCP-1 in renal tubuli, probably triggered by an increase in the
      leakage of plasma protein from glomerular capillary to tubular fluid, may
      contribute to renal tubular damage and accelerate the progression of diabetic
      nephropathy. To test this hypothesis, we examined urinary excretion levels of MCP
      1 and N-acetylglucosaminidase (NAG), a sensitive marker of renal tubular damage,
      in Japanese Type II diabetic patients with normoalbuminuria (n=29),
      microalbuminuria (n=25), and macroalbuminuria (n=18). The median urinary
      excretion level of MCP-1 in patients with macroalbuminuria (394.4 ng/g
      creatinine) was significantly elevated compared to the levels in patients with
      normoalbuminuria and microalbuminuria (159.6 and 193.9 ng/g creatinine,
      respectively). Furthermore, the urinary MCP-1 excretion level was positively
      correlated with urinary excretion levels of albumin (r=.816, P<.001) and NAG
      (r=.569, P<.001) in all subjects. These results suggest that MCP-1 is produced in
      renal tubular cells and released into urine in proportion to the degree of
      proteinuria (albuminuria), and that increased MCP-1 expression in renal tubuli
      contributes to renal tubular damage. Therefore, we conclude that heavy
      proteinuria itself may accelerate the progression of diabetic nephropathy by
      increasing the MCP-1 expression in renal tubuli.

PMID- 12505751
TI  - Serum levels of non-carboxymethyllysine advanced glycation endproducts are
      correlated to severity of microvascular complications in patients with Type 1
      diabetes.
AB  - We investigated whether serum levels of N-(carboxymethyl)lysine (CML), non-CML
      advanced glycation endproducts (AGEs), or pentosidine are associated with
      severity of diabetic microvascular complications in patients with Type 1
      diabetes. Serum levels of CML, non-CML AGE, and pentosidine were measured by an
      enzyme-linked immunosorbent assay in 38 males and 47 females aged 31+/-8 years
      (mean+/-S.D.) with Type 1 diabetes for 18.7+/-7.0 years. There was a significant
      correlation between serum levels of CML or non-CML AGE and current HbA(1c) level
      (P<.01 and P<.05, respectively). The serum levels of non-CML AGE, but not CML or
      pentosidine, were significantly increased as normal renal status advanced to
      microalbuminuria, clinical nephropathy, and hemodialysis (P<.0001) and were
      positively correlated with urinary albumin excretion (UAE) in patients with Type
      1 diabetes (P<.0001). A significant elevation of serum non-CML AGE was found in
      association with the severity of diabetic retinopathy (P<.0001). We found in the
      present study that CML levels were also increased in the stage of simple
      retinopathy, the early stage of clinically evident retinopathy (P<.05). Serum
      levels of non-CML AGE were significantly associated with the severity of diabetic
      nephropathy and retinopathy, suggesting a role of non-CML AGE in the progression
      of microvascular complications in patients with Type 1 diabetes. Since serum
      levels of CML were significantly increased in patients with simple retinopathy,
      CML may participate in the initiation of diabetic retinopathy.

PMID- 12505752
TI  - The mechanisms of inhibitory actions of gliclazide on neutrophils-endothelial
      cells adhesion and surface expression of endothelial adhesion molecules mediated
      by a high glucose concentration.
AB  - BACKGROUND: We previously reported that culture of endothelial cells in the
      presence of high glucose concentrations (27.8 and 55.5 mM) increase neutrophils
      adhesion because of the increase in endothelial adhesion molecules expression via
      activation of a protein kinase C (PKC) pathway. The antidiabetic sulfonylurea
      gliclazide, but not glibenclamide, inhibited these events, but the mechanisms
      involved were not clarified then. We present hereafter the results of further
      investigations of that effect with special reference to PKC activation. METHODS:
      Human umbilical vein endothelial cells (HUVEC) were cultured for 48 h in a
      glucose-rich medium and neutrophils from healthy volunteers were then added and
      allowed to adhere for 30 min. Adhered neutrophils were quantified by measuring
      myeloperoxidase (MPO) activities and the surface expression of endothelial
      adhesion molecules was determined by enzyme immunoassay. RESULTS: Culture in the
      presence of a high glucose concentration (27.8 mM for 48 h) increased neutrophils
      endothelial cells adhesion and the surface expression of intercellular adhesion
      molecule-1 (ICAM-1), P-selectin, and E-selectin on the endothelial cells. These
      phenomena were significantly inhibited by gliclazide (20 microM). On the other
      hand, phorbol 12-myristate 13-acetate (PMA), a PKC activator, had an effect
      similar to a high glucose concentration and that effect was also inhibited by
      gliclazide. CONCLUSIONS: These data suggest that gliclazide inhibits high glucose
      mediated neutrophils-endothelial cells adhesion and expression of endothelial
      adhesion molecules through inhibition of a PKC pathway.

PMID- 12505753
TI  - Ob/ob mice as a model of delayed gastric emptying.
AB  - Diabetic gastroparesis is a well-recognized delay of gastric emptying in diabetic
      patients. We assessed the gastric emptying rate in ob/ob mice, a genetic model of
      obesity and diabetes. The basal gastric emptying rate in 22- to 27-week-old ob/ob
      mice was significantly lower than that in 10- to 11-week-old ob/ob mice (P<.01).
      Our results indicate that the ob/ob mice are a useful model not only of glucose
      intolerance but also of delayed gastric emptying as a diabetic complication.

PMID- 12505754
TI  - Treadmill exercise increases cell proliferation in dentate gyrus of rats with
      streptozotocin-induced diabetes.
AB  - Diabetes mellitus is a common and serious metabolic disorder in humans.
      Streptozotocin (STZ)-induced diabetic rats were shown to produce a significant
      reduction in the number of proliferating cells in the dentate gyrus. In the
      present study, the effect of treadmill exercise on cell proliferation in the
      dentate gyrus of rats with STZ-induced diabetes was investigated via
      immunohistochemistry. Male Sprague-Dawley rats were divided into four groups: the
      control-rest group, the control-exercise group, the diabetes-rest group, and the
      diabetes-exercise group. Each of the animals of the diabetes groups was given a
      single injection of STZ (50 mg/kg) intraperitoneally. All animals were injected
      with 5-bromo-2'-deoxyuridine (50 mg/kg) for six consecutive days, starting on the
      second day after STZ injection, and rats of the exercise groups were made to run
      on treadmill for 30 min each day over the same period. On the eighth day of the
      experiment, all animals were sacrificed. In the present results, it was shown
      that cell proliferation in the dentate gyrus is suppressed under diabetic
      conditions, and that treadmill is effective in enhancing hippocampal granular
      cell proliferation in rats with STZ-induced diabetes. These results raise the
      possibility that treadmill exercise is of help in the alleviation of the central
      neural sequelae of diabetes mellitus.

PMID- 12505755
TI  - Identification and characterization of high glucose and glucosamine responsive
      element in the rat osteopontin promoter.
AB  - We have previously reported that high glucose stimulates osteopontin (OPN)
      expression via a protein kinase C-dependent pathway and a hexosamine pathway in
      cultured rat aortic smooth muscle cells (SMCs) [Biochem. Biophys. Res. Commun.
      258 (1999) 722.]. In the present study, we carried out functional OPN promoter
      assays using the luciferase expression vector system in cultured rat aortic SMCs
      to determine a high glucose/glucosamine responsive element. An extensive deletion
      analysis of the 5'-flanking region of the rat OPN gene revealed that an element
      involved in high glucose and glucosamine responses was present within a region
      between -112 and -62 bp of the OPN promoter. This region is highly conserved in
      the rat, mouse, and human promoters and contains a number of consensus regions,
      including an E-box and a GC-rich region. Mutation of the E-box or the GC-rich
      region resulted in a significant loss of both high glucose and glucosamine
      responses. These results suggest that two cis-acting elements, the E-box and the
      GC-rich region, are involved at least partly in high glucose/glucosamine
      stimulated transcription of the rat OPN gene.

PMID- 12505756
TI  - The impact of ethnicity on type 2 diabetes.
AB  - The rapid increase of diabetes prevalence in the US population and across all
      westernized world has been associated with environmental changes that promote
      obesity. Although dietary factors, such as total caloric intake, relative excess
      of dietary saturated fats content and lack of fibers, together with reduced level
      of physical activity clearly determine the main features of the "obesogenic"
      environment typical of "western" societies, the impact of lifestyle factors on
      obesity and diabetes appears to differ in various ethnic groups. Although ethnic
      related differences in lifestyle factors may account for some of the
      predisposition to obesity and diabetes of various ethnic groups, genetic factors
      may play a more determinant role. These observations pose important public health
      questions in regard to strategies for treatment and prevention of diabetes both
      within the multiethnic US population and in the population of origin of various
      ethnicities. The elucidation of the pathophysiologic mechanisms responsible for
      the heterogeneous relationship between obesity and type 2 diabetes in various
      ethnicities may give important contributions to better understand the complex
      mechanisms involved in the development of this disease. This review examines
      epidemiological and pathophysiological aspects of the interaction between
      environment and ethnic predisposition to type 2 diabetes.

PMID- 12505757
TI  - Interpretation of secondary electron images obtained using a low vacuum SEM.
AB  - Charging of insulators in a variable pressure environment was investigated in the
      context of secondary electron (SE) image formation. Sample charging and ionized
      gas molecules present in a low vacuum specimen chamber can give rise to SE image
      contrast. "Charge-induced" SE contrast reflects lateral variations in the charge
      state of a sample caused by electron irradiation during and prior to image
      acquisition. This contrast corresponds to SE emission current alterations
      produced by sub-surface charge deposited by the electron beam. "Ion-induced"
      contrast results from spatial inhomogeneities in the extent of SE signal
      inhibition caused by ions in the gaseous environment of a low vacuum scanning
      electron microscope (SEM). The inhomogeneities are caused by ion focusing onto
      regions of a sample that correspond to local minima in the magnitude of the
      surface potential (generated by sub-surface trapped charge), or topographic
      asperities. The two types of contrast exhibit characteristic dependencies on
      microscope operating parameters such as scan speed, beam current, gas pressure,
      detector bias and working distance. These dependencies, explained in terms of the
      behavior of the gaseous environment and sample charging, can serve as a basis for
      a correct interpretation of SE images obtained using a low vacuum SEM.

PMID- 12505758
TI  - Backscattered electron imaging and scanning transmission electron microscopy
      imaging of multi-layers.
AB  - Experimental and theoretical results on image contrast of semiconductor multi
      layers in scanning electron microscopy investigation are reported. Two imaging
      modes have been considered: backscattered electron imaging of bulk specimen and
      scanning transmission imaging of thinned specimens. The following main results
      have been reached. The image resolution of the multi-layers is, in both cases,
      defined by the probe size. The contrast, governed by density and atomic number
      differences, is affected by the size of the interaction volume in backscattered
      electron imaging and by the beam broadening in scanning transmission. Operating
      in the scanning transmission mode, the contrast of bright field images can be
      easily related to local variation in atomic number and density of the specimen
      while the dark field image contrast is strongly affected by electron beam energy,
      detector collection angles and specimen thickness. All these factors are able to
      produce contrast reversals that are difficult to explain without the support of a
      suitable simulation code.

PMID- 12505759
TI  - Reconstruction of composite in-line electron holograms using a small emission
      cone.
AB  - We report a new method that gives atomic resolution in the reconstruction of
      simulated holograms in theoretical low energy electron point source (LEEPS)
      microscopy, and that uses a screen size that is commensurate with screen sizes
      used in experimental LEEPS. The method exploits the spherical symmetry in the
      electron waves emerging from the source. We compare holograms obtained by
      rotating the screen about an axis passing through the point source as opposed to
      rotating the atomic cluster in the opposite sense about the same axis. We show
      that, by generating and combining simulated holograms obtained by rotating the
      cluster, with the screen held fixed, a composite hologram, comprised of the
      individual holograms, captures enough information that atomic resolution in the
      reconstructions is obtained. A key feature is to choose the rotations to optimize
      the collective interference pattern on the composite hologram. This results in
      sharper resolution while using a considerably smaller screen size; results are
      reported for a screen size about ten times smaller than screen sizes typically
      used in theoretical LEEPS. The method used gives commensurate or better
      resolution on comparison to results obtained using the larger screen size.
      Possible implications for experimental LEEPS are briefly discussed.

PMID- 12505760
TI  - Apertureless near-field optical microscopy of metallic nanoparticles.
AB  - Image formation in apertureless near-field optical microscopes employing
      evanescent-wave excitation is studied quantitatively as a function of the
      polarisation and the wavelength of the excitation. Aggregate Mie theory is used
      to describe the probe-sample interactions self-consistently, including
      retardation. Only p-polarised excitation yields images, which closely reproduce
      the sample, and the contrast is much higher in this case than for s-polarised
      waves. Particular attention is paid to the case of imaging of metallic
      nanoparticles, for which local and nonlocal versions of aggregate Mie theory are
      compared. Nonlocality arises from the excitation of longitudinal bulk plasmons at
      the particle surface. It is shown that this effect is essential in the imaging of
      such particles and implies comparatively rapid convergence, in contrast to the
      local theory. The converged images calculated within the nonlocal theory resemble
      the results of the local theory, when, arbitrarily, within the latter only dipole
      dipole interactions are taken into account. Significant qualitative and
      quantitative differences, however, are shown to exist. Signal and contrast
      enhancements due to resonant excitation of surface plasmon polaritons are studied
      quantitatively using the results of the converged nonlocal theory.

PMID- 12505761
TI  - Quantitative characterisation of chemical inhomogeneities in Al-Ag using high
      resolution Z-contrast STEM.
AB  - The incoherent imaging model is applied to interpret high-resolution Z-contrast
      micrographs. A simple method for a column-by-column resolved characterisation of
      Ag-rich precipitates in Al-Ag is developed. No information on the detailed
      imaging process is required. Evaluating the high-angle scattering intensities of
      Al and Ag by image analysis, the number of Ag atoms contained in individual
      atomic columns can be determined accurately and moreover, the thickness of the
      thin foil can be calculated. Multislice simulations confirm the broad validity of
      the incoherent imaging model for Z-contrast STEM and are used to check the method
      presented. Finally, the image analysis is applied to experimental Z-contrast
      images of Guinier-Preston zones in Al-3 at% Ag. The Ag content of the individual
      atomic columns can be determined with an accuracy better than +/-10%.

PMID- 12505762
TI  - Measuring the PSF from aperture images of arbitrary shape--an algorithm.
AB  - A new algorithm for determining the point spread function (PSF) of digital
      imaging systems is presented. The input is an image of an aperture whose shape
      need not be regular. The aperture shape is refined to an effective sub-pixel
      resolution and the PSF of the system is determined by de-convolution, assuming
      uniform illumination and a step function edge. The method has been tested on
      theoretical aperture images of varying shape and PSF, with and without noise.
      Depending on the degree of noise, a known PSF can be recovered to an accuracy of
      between 0.2 and 0.8%. Some typical results are given for a Gatan Image Filter
      with a 794 YAG multiscan camera on a Philips EM 430 transmission electron
      microscope at 200 and 300 kV. An example of a de-convoluted convergent beam
      electron diffraction pattern is included. The algorithm tolerates a small amount
      of de-focus.

PMID- 12505763
TI  - Semiconductor dopant profiling by off-axis electron holography.
AB  - Silicon wafers with a complex but known dopant profile were used to explore
      possible methods for improving the reliability of off-axis electron holography
      for quantitative determination of electrostatic potential profiles in doped
      semiconductor devices. The variability of results from nominally identical
      structures was attributed to local charging and associated external fields,
      forcing the development of a more robust approach to hologram analysis that
      incorporated an additional phase correction factor rather than rely on vacuum for
      phase flattening. Consistent results in close agreement with simulated profiles
      based on measured dopant distributions could then be obtained. Carbon coating was
      shown to be effective in reducing accumulation of charge caused by emission of
      secondary electrons. Overall, this work demonstrates that reliable potential
      profiles from unbiased samples should be obtainable on a routine basis provided
      that regions suitable for flattening of the phase profile can be identified.

PMID- 12505764
TI  - Recall performance, plasma cortisol and plasma norepinephrine in normal human
      subjects.
AB  - This study investigated hypothalamic-pituitary-adrenal (HPA)-axis and sympathetic
      nervous system (SNS) correlates of recall performance in normal human subjects.
      Twenty-two normal human subjects were given one memory task: short-term recall of
      unrelated non-organizable lists of neutral words, in immediate recall conditions.
      Two types of memory were individualized: measures reflecting effortful processing
      and measures reflecting automatic processing, which were related to 3 daytime
      plasma cortisol (CORT) and plasma NE values, and assessed after venipuncture. It
      was hypothesized that plasma CORT is positively related and plasma norepinephrine
      (NE) is negatively related to effortful processing. Pearson correlation was
      computed and regression analysis was performed. Positive correlation appeared
      between plasma CORT values and negative correlation appeared between plasma NE
      values and measures reflecting effortful processing. However, stepwise multiple
      regression analysis showed that only morning plasma CORT values are functionally
      positively and afternoon plasma NE values are functionally negatively related to
      effortful processing. This suggests that morning HPA-axis activities enhance and
      afternoon SNS activities inhibit effortful processing.

PMID- 12505765
TI  - Prestimulus modification of the startle reflex: relationship to personality and
      physiological markers of dopamine function.
AB  - Prepulse inhibition (PPI), a measure of sensorimotor gating, is regulated by
      dopamine (DA) in rodents. We examined the relationship of PPI in humans to
      putative markers of brain DA function: (1) novelty seeking (NS; Cloninger's
      Tridimensional Personality Questionnaire (TPQ)), which is associated with
      specific DA receptor subtypes, and is reduced in Parkinson's Disease; (2) blink
      rate, which is increased in primates by DA agonists, and is reduced in
      Parkinson's Disease. PPI, TPQ and blink rate were measured in 79 normal adult
      males. A significant negative correlation was observed between resting blink rate
      and mean PPI, but not between NS and PPI. Blink rate correlated positively with
      resting EMG level, but this did not account for the relationship between blink
      rate and PPI. In normal male humans, PPI is inversely related to a physiological
      marker of resting DA tone (blink rate), but not to a putatively DA-linked
      personality trait (high NS).

PMID- 12505766
TI  - Lead stimulus modality change and the attentional modulation of the acoustic and
      electrical blink reflex.
AB  - Two experiments investigated the effects of the sensory modality of the lead and
      of the blink-eliciting stimulus during lead stimulus modality change on blink
      modulation at lead intervals of 2500 and 3500 ms. Participants were presented
      with acoustic, visual, or tactile change stimuli after habituation training with
      lead stimuli from the same or a different sensory modality. In Experiment 1,
      latency and magnitude of the acoustic blink were facilitated during a change to
      acoustic or visual lead stimuli, but not during a change to tactile lead stimuli.
      After habituation to acoustic lead stimuli, blink magnitude was smaller during
      tactile change stimuli than during habituation stimuli. The latter finding was
      replicated in Experiment 2 in which blink was elicited by electrical stimulation
      of the trigeminal nerve. The consistency of the findings across different
      combinations of lead stimulus and blink-eliciting stimulus modalities does not
      support a modality-specific account of attentional blink modulation. Rather,
      blink modulation during generalized orienting reflects modality non-specific
      processes, although modulation may not always be found during tactile lead
      stimuli.

PMID- 12505767
TI  - Impairment in activation of a frontal attention-switch mechanism in schizophrenic
      patients.
AB  - The present study addresses the difference in activities of frontal and temporal
      mismatch negativity (MMN) generators between healthy controls and schizophrenic
      patients. Auditory MMNs were measured from 13 medicated schizophrenic patients in
      a post-acute phase and 12 healthy controls. The probabilities of the standard
      stimuli were, in different experimental blocks, 95, 90, 80 or 70%. The mean
      amplitude of the MMN recorded at Fz was significantly smaller in schizophrenic
      patients than healthy controls only in the conditions with high probability of
      standard stimuli, while that recorded at mastoid sites was not different in any
      condition. The present study suggested that schizophrenic patients might fail to
      cause involuntary attention switch to stimulus change reflected in the lowered
      MMN amplitude recorded at Fz; whereas the patients might index an adequate
      detection of the deviant event reflected by the similar amplitude of MMN recorded
      at mastoid sites.

PMID- 12505768
TI  - The relationship between P3 and neuropsychological function in an adult life span
      sample.
AB  - The relationship of P3 to age and neuropsychological performance was investigated
      in a sample of 71 well-functioning adults ranging in age from 21.8 to 94.7 years.
      ERPs were recorded while the participants performed an auditory two-stimuli
      oddball task in which the rare tones were to be counted. The Wechsler Abbreviated
      Scale of Intelligence (WASI) and the digit span subtest from the Wechsler Adult
      Intelligence Scale-R (WAIS-R) were administered. Regression analyses showed
      significant, linear effects of age on P3 latency and amplitude. Significant
      relationships between P3 and neuropsychological measures were found, in that P3
      latency correlated moderately in predictable ways with scores on matrices, block
      design, and digit span. Overall, these relationships are best characterized by a
      linear function, but a non-linear component is involved in the relationship
      between P3 latency and fluid tests. Finally, a linear relationship between ERP
      components and age was found, while a curvilinear relationship was found between
      age and block design and matrices, respectively. There appears to be either
      partially different functions or structures underlying performance on these
      tests, the P3 component and performance on neuropsychological tests, or one must
      assume some variant of a multiplicative, as opposed to an additive, model of
      cognition.

PMID- 12505769
TI  - Determination of dextromethorphan and its metabolite dextrorphan in human urine
      by capillary gas chromatography without derivatization.
AB  - A sensitive, simple and accurate method was developed for determination of
      dextromethorphan (DM) and dextrorphan (DT) in human urine by capillary gas
      chromatography without derivatization. After an oral dose of 30 mg DM, urine
      samples were collected and extracted, then analyzed on 0.22 mmx17 m HP-1
      capillary column. DM and its metabolite DT were analyzed simultaneously with good
      separation. Docosane was used as the internal standard (I.S.). The detector used
      was flame ionization detector (FID). There was a linear relationship between peak
      area ratios of analytes to I.S. and concentration of analytes over the
      concentration range 0.37-7.38 micromol/l for DM and 0.39-77.8 micromol/l for DT.
      The recovery was 88.1 approximately 103.9% for DM and 86.7 approximately 96.8%
      for DT. The within-day and between-day coefficients of variation were less than
      7.4 and 7.3% (RSD) for the assay of DM and DT in urine, respectively. The limits
      of detection (LOD) were 0.30 micromol/l for DM and 0.16 micromol/l for DT. The
      limits of quantitation (LOQ) were 0.37 micromol/l (RSD<6%) for DM and 0.39
      micromol/l (RSD<7%) for DT. The method has been applied to determine the
      oxidative phenotypes of cytochrome P450 2D6 (CYP2D6) in a Chinese population with
      metabolic ratio of DM in human urine.

PMID- 12505770
TI  - Determination of plasma topotecan and its metabolite N-desmethyl topotecan as
      both lactone and total form by reversed-phase liquid chromatography with
      fluorescence detection.
AB  - Topotecan (TPT) undergoes hepatic N-demethylation forming N-desmethyl topotecan
      (NDS). To evaluate the effect of drug-drug interactions on NDS disposition in
      children receiving TPT we developed and validated a sensitive and specific HPLC
      fluorescence detection method for lactone and total (lactone plus carboxylate)
      TPT and NDS. Deproteinized plasma is vortexed, centrifuged, and the methanolic
      extract diluted with water for the lactone form of NDS and TPT or diluted with
      1.5% phosphoric acid for NDS and TPT total. A 100 microL sample is injected onto
      a Varian ChromGuard RP column attached to an Agilent SB-C(18) reversed-phase
      analytical column held at 50 degrees C. The mobile phase (flow-rate, 0.8 mL/min)
      consists of methanol-aqueous buffer (27:73, v/v) (75 mM potassium phosphate and
      0.2% triethylamine, pH 6.5). TPT and NDS were detected with excitation and
      emission wavelengths set at 376 and 530 nm, respectively. The standard curves for
      both forms of TPT ranged from 0.25 to 80 ng/mL, and for NDS ranged from 0.10 to
      8.0 ng/mL. Within-day and between-day precision (% RSD) was </=4% for TPT and
      </=6.2% for NDS, respectively. Within-day and between-day percentage error ranged
      from 1.4 to 6.3% and from 1.4 to 2.4% for TPT, and from 1.6 to 3.1% and from 0.0
      to 3.7% for NDS, respectively. No significant on-column conversion from TPT or
      NDS lactone to carboxylate was observed. With one method we can measure lactone
      and total TPT and NDS with adequate sensitivity to allow for evaluation of the
      disposition of these compounds in children receiving TPT.

PMID- 12505771
TI  - Highly sensitive determination of saquinavir in biological samples using liquid
      chromatography-tandem mass spectrometry.
AB  - A selective and sensitive method for the determination of the HIV protease
      inhibitor saquinavir in human plasma, saliva, and urine using liquid-liquid
      extraction and LC-MS-MS has been developed, validated, and applied to samples of
      a healthy individual. After extraction with ethyl acetate, sample extracts were
      chromatographed isocratically within 5 min on Kromasil RP-18. The drug was
      detected with tandem mass spectrometry in the selected reaction monitoring mode
      using an electrospray ion source and 2H(5)-saquinavir as internal standard. The
      limit of quantification was 0.05 ng/mL. The accuracy of the method varied between
      -1 and +10% (SD within-batch) and the precision ranged from +4 to +10% (SD batch
      to-batch). The method is linear at least within 0.05 and 87.6 ng/mL. After a
      regular oral dose (600 mg) saquinavir concentrations were detectable for 48 h in
      plasma and were well correlated with saliva concentrations (r(2)=0.9348, mean
      saliva/plasma ratio 1:15.1). The method is well suited for low saquinavir
      concentrations in different matrices.

PMID- 12505772
TI  - Mass spectrometric detection of nodularin and desmethylnodularin in mussels and
      flounders.
AB  - Samples of mussels and flounders from the Baltic Sea were analysed for nodularin
      content on two different LC-MS instruments (triple quadrupole and ion trap). The
      triple quadrupole instrument was well suited for the quantitative analysis. The
      limit of detection in the selected ion recording mode was 5 pg and in the
      multiple reactant monitoring mode 500 pg on column for extracts of Nodularia
      spumigena. The fragmentation patterns of nodularin-R and desmethylnodularin-R
      were recorded and shown to be similar to those of microcystins. LC-MS proved to
      be an excellent tool for the analyses of cyanobacterial hepatotoxins in complex
      matrices.

PMID- 12505773
TI  - Determination of kanamycin in serum by solid-phase extraction, pre-capillary
      derivatization and capillary electrophoresis.
AB  - An effective method based on solid-phase extraction (SPE) and capillary
      electrophoresis (CE) for the determination of kanamycin in human serum was
      developed and validated. Off-line SPE was employed for the isolation of kanamycin
      from serum on a carboxypropyl-bonded phase (CBA) weak cation-exchange cartridge.
      A mixture of 0.2 M borate (pH 10.5)-methanol (50:50, v/v) was used as analyte
      eluting solvent. After pre-capillary derivatization with o
      phthalaldehyde/mercaptoacetic acid reagent, the sample was analyzed by CE with a
      separation buffer of 30 mM borax, pH 10.0, containing 16% (v/v) methanol. A
      linear response over the concentration range 5-40 microgram/ml was obtained with
      a detection limit of 2 microgram/ml. Intra-day and inter-day precision were 6.2
      and 10.3% RSD, respectively. Recoveries of approximately 90% were found. For the
      determination of lower levels of kanamycin (<5 microgram/ml), NH(4)OH (25%, w/v)
      methanol (30:70, v/v) was used for analyte elution. After evaporation,
      reconstitution and derivatization, the sample was analyzed by on-line field
      amplified sample stacking (FASS) CE. Good linearity in the concentration range
      0.4-5 microgram/ml was obtained with a detection limit of 0.1 microgram/ml. Intra
      day and inter-day RSD were 3.4 and 11.2%, respectively. Recoveries of
      approximately 60% were found. The method was successfully applied to the analysis
      of kanamycin in sera of tuberculosis patients at peak level and trough level
      concentrations.

PMID- 12505774
TI  - Method for monitoring alginate released in biological fluids by high-performance
      anion-exchange chromatography with pulsed amperometric detection.
AB  - The use of alginate-entrapped cells in cell therapy requires a method for
      monitoring possible released compound within biological fluids following either
      their implantation or inoculation in artificial organs. Oligomannuronic and
      oligoguluronic acids were prepared by enzymatic depolymerization with alginate
      lyase from Pseudomonas alginovora, characterized by high-performance anion
      exchange chromatography with pulsed amperometric detection and quantitated in
      human, pig and rabbit blood, urine and tissue samples. The method was tested for
      linearity and detection limit, accuracy, intra- and inter-day precision. The
      limit of detection was 3 microgram/ml in both urine and plasma and 5 mg/g of
      tissues. The relative standard deviations (RSDs) of intra-day precision were 6.0
      16.6% and 4.8-8.7% in plasma and urine, respectively; the RSDs of inter-day
      precision were 5.1-14.4% and 5.0-11.6% in plasma and urine, respectively. Thus,
      this method appears suitable for the measurement of released alginate from
      entrapped cells used in cell therapy.

PMID- 12505775
TI  - Simultaneous determination of creatinine and pseudouridine concentrations in
      bovine plasma by reversed-phase liquid chromatography with photodiode array
      detection.
AB  - A simple, rapid method for the simultaneous determination of creatinine and
      pseudouridine in bovine plasma is described. Plasma was de-proteinised,
      concentrated, and chromatographed for 15 min on a C(18) column. Analytes were
      detected at an optimum wavelength (262 nm) and the internal standard (cimetidine)
      was detected at 220 nm. The pH of analysis was between 6.5 and 7 where both
      analytes exist in single chemical forms giving maximum accuracy. Recoveries of
      both analytes were above 96%. Lowest detectable amounts of creatinine and
      pseudouridine were 0.28 nmol and 9.0 pmol, and the typical levels detected (+/
      SD) were 60 (+/-2.8) and 2.3 (+/-0.10) micromol/L, respectively.

PMID- 12505776
TI  - Application of improved iodine-azide procedure for the detection of thiouracils
      in blood serum and urine with planar chromatography.
AB  - The application of iodine-azide reaction for the determination of thiouracils in
      thin-layer chromatography and high-performance thin-layer chromatography is
      described. The developed plates were sprayed with a freshly prepared mixture of
      sodium azide, adjusted to a proper pH, and starch solution, and exposed to iodine
      vapour for 5 s. The detection limits were established at pmol level. The factors
      depending on the detection limits were described. A comparison of iodine-azide
      tests reaction with other procedures is presented. The developed method was
      applied to detection of thiouracils in blood serum and urine. The possibility of
      detection of a thiouracils mixture was demonstrated.

PMID- 12505777
TI  - Supercoiled plasmid DNA: selective purification by thiophilic/aromatic
      adsorption.
AB  - Separation of the different plasmid isoforms is a major challenge in purifying
      plasmid DNA. We describe a new type of biochemical interaction that occurs in the
      presence of high concentrations of lyotropic salt and results in the selective
      adsorption of supercoiled plasmid DNA to aromatic thioether ligands. Under well
      defined conditions, these ligands are capable of separating supercoiled plasmid
      DNA (ccc) from its isoform, i.e. open circular (oc) form. Integrated in a
      process, preceded by group separation and followed by anion-exchange
      chromatography, this new purification method may facilitate the production of
      highly purified supercoiled plasmid DNA for use in gene therapy and DNA vaccine
      applications.

PMID- 12505778
TI  - Quantitative determination of rivastigmine and its major metabolite in human
      plasma by liquid chromatography with atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - A sensitive, specific, accurate and reproducible LC-MS-MS method was developed
      and validated for the simultaneous determination of rivastigmine and its major
      metabolite NAP 226-90 in human plasma according to International Regulatory
      Requirements. After addition of their respective labelled internal standards, the
      compounds were extracted from plasma using methyl-tert.-butyl ether at basic pH
      with a simultaneous derivatization of NAP 226-90 with propionic anhydride, and
      backextracted into an acidic solution. After re-extraction the compounds were
      analyzed on a 3-micrometer Purospher Star RP-18 column interfaced with a MDS
      Sciex API 3000 triple quadrupole mass spectrometer. Positive atmospheric chemical
      ionization was employed as the ionization source. The analytes and their internal
      standards were detected by use of multiple reaction monitoring mode. Intra- and
      inter-day accuracy and precision were found suitable over the range of
      concentrations between 0.200 and 30.0 ng/ml. The LC-MS-MS method was
      crossvalidated with a previously developed in-house GC-MS method by the analysis
      of plasma samples obtained from patients after administration of Exelon((R))
      capsules and showed excellent correlation between the methods.

PMID- 12505780
TI  - Simple liquid chromatographic method for the determination of physostigmine and
      its metabolite eseroline in rat plasma: application to a pharmacokinetic study.
AB  - Physostigmine, an anticholinergic drug, and its metabolite eseroline can be
      quantitated by high-performance liquid chromatography (HPLC) with photodiode
      array detection. After addition of the structurally related internal standard (-)
      N-methylphysostigmine, rat plasma samples were extracted and cleaned using a
      Varian Bond Elut C(18) column. The methanol-ammonia (98:2) eluate was evaporated
      to dryness and reconstituted with 0.01 M sodium dihydrogenphosphate (pH 3).
      Physostigmine and eseroline were separated on an Alltech Ultrasphere Silica
      column (250x4.6 mm I.D.; particle size 5 micrometer) at a flow-rate of 1 ml/min,
      with a mobile phase of 0.01 M sodium dihydrogenphosphate (pH 3)-acetonitrile
      (85:15). The limits of detection were 10 and 25 ng/ml for physostigmine and
      eseroline, respectively; the signal-to-noise ratio for this concentration was
      approximately 3:1. Spiked rat plasma containing 0.1-2.5 microgram/ml of
      physostigmine and eseroline gives good linearity. The average percentage recovery
      from five spiked plasma samples was 88.0+/-2.9 and 61.1+/-5.6% for physostigmine
      and eseroline, respectively. Within the concentration range 0.1-2.5 microgram/ml,
      the within-day precision was 1.9-8.3 and 3.0-7.7% for physostigmine and
      eseroline, respectively, and the between-day precision was 4.1-9.3 and 3.7-11%
      for physostigmine and eseroline, respectively. The method is rapid, simple and
      reliable, thus it is suitable for pharmacokinetic studies in the rat.

PMID- 12505779
TI  - High-performance thin-layer chromatography-bioautography for multiple antibiotic
      residues in cow's milk.
AB  - An analytical method to identify and quantify multiple antibiotic residues
      (chloramphenicol, ampicillin, benzylpenicillin, dicloxacillin and erythromycin)
      in cow's milk by high-performance thin-layer chromatography (HPTLC) combined with
      bioautography was developed. The test microorganism used for bioautography was
      Bacillus subtilis ATCC 6633. Antibiotic residues were extracted with
      acetonitrile, fat eliminated with petroleum ether and residues isolated with
      dichloromethane The sensitivity of the method guarantees the detection of the
      above-mentioned antibiotics at levels below maximum residue limits (MRL) allowed
      for milk. Percentage recoveries ranged between 90 and 100%, with coefficients of
      variation between 7.2 and 21.3%. Some advantages of this methodology over thin
      layer chromatography (TLC)/bioautography are also discussed.

PMID- 12505781
TI  - Simultaneous determination of nine antiretroviral compounds in human plasma using
      liquid chromatography.
AB  - A rapid, sensitive and specific high-performance liquid chromatographic (HPLC)
      method using UV detection was developed for the determination of nine
      antiretroviral compounds commonly found in plasma from patients receiving
      antiretroviral therapy. Analytes include indinavir, saquinavir, ritonavir,
      amprenavir, lopinavir, delavirdine, efavirenz, nelfinavir and its M8 metabolite.
      Analytes were isolated from plasma using tert.-butyl methyl ether and separation
      achieved via reversed-phase liquid chromatography on a C(8) column with a
      gradient mobile phase. Detection at 210 nm provided adequate sensitivity. Limit
      of quantification is 50 ng/ml and all analytes demonstrated linearity across 50
      10000 ng/ml from a single 200-microliter plasma sample. Recovery from plasma was
      consistently high (>80%). This novel HPLC methodology allows us to simultaneously
      determine plasma concentrations of nine antiretrovirals, including lopinavir, in
      HIV-infected patients on a single HPLC system.

PMID- 12505782
TI  - Capillary electrophoretic enzyme immunoassay with electrochemical detection using
      a noncompetitive format.
AB  - A capillary electrophoretic enzyme immunoassay with electrochemical detection (CE
      EIA-ED) using a noncompetitive format has been developed. In this method, antigen
      (Ag) reacts with an excess amount of horseradish peroxidase (HRP)-labeled
      antibody (Ab*). The free Ab* and the bound Ag-Ab* complex produced in the
      solution are separated by capillary zone electrophoresis in a separation
      capillary. Then they catalyze enzyme substrate 3,3',5,5'-tetramethylbenzide
      (TMB(Red)) and H(2)O(2) in a reaction capillary following the separation
      capillary. The reaction product, TMB(Ox), can be determined using amperometric
      detection on a carbon fiber microdisk bundle electrode at the outlet of the
      reaction capillary. Due to the amplification of the enzyme, a significant amount
      of TMB(Ox) can be produced for detection. Therefore, the limit of detection (LOD)
      of CE-EIA-ED is very low. A tumor marker (CA15-3) was used as a model, in order
      to test the method. The concentration LOD of CA15-3 is 0.024 U/ml, which
      corresponds to a mass detection limit of 1.3x10(-7) U.

PMID- 12505783
TI  - Gas chromatography-mass spectrometry of cis-9,10-epoxyoctadecanoic acid (cis
      EODA). I. Direct evidence for cis-EODA formation from oleic acid oxidation by
      liver microsomes and isolated hepatocytes.
AB  - Oleic acid, cis-9-octadecenoic acid, is the major fatty acid in mammals. Its
      oxide, cis-9,10-epoxyoctadecanoic acid (cis-EODA), has been identified in blood
      and urine of humans, its origin is, however, still unknown. Lipid peroxidation
      and enzyme-catalyzed epoxidation of oleic acid are two possible sources. In the
      present article, we investigated by HPLC and GC-MS whether cis-EODA is formed
      enzymatically from oleic acid by the cytochrome P450 (CYP) system. Oleic acid,
      cis-EODA and its hydratation product threo-9,10-dihydroxyoctadecanoic acid (threo
      DiHODA) were quantitated by HPLC as their p-bromophenacyl esters. For structure
      elucidation by GC-MS, the pentafluorobenzyl (PFB) esters of these compounds were
      isolated by HPLC and converted to their trimethylsilyl ether derivatives. Liver
      microsomes of rats, rabbits and humans oxidized oleic acid into cis-EODA. This is
      the first direct evidence for the enzymatic formation of cis-EODA from oleic
      acid. The epoxidation of oleic acid was found to depend on CYP, NADPH+H(+), and
      O(2). cis-EODA was measurable in incubates of liver microsomes for up to 30 min
      of incubation. Maximum cis-EODA concentrations were reached after 5-7 min of
      incubation and found to depend upon oleic acid concentration. Isolated rat
      hepatocytes hydratated cis-EODA into threo-DiHODA which was further converted to
      unknown metabolites. However, from incubation of oleic acid with these cells we
      could not detect threo-DiHODA or cis-EODA. Our study suggests that circulating
      and excretory cis-EODA may originate, at least in part, from CYP-catalyzed
      epoxidation of oleic acid. GC-MS of intact cis-EODA as its PFB ester in the
      negative-ion chemical ionization mode should be useful in investigating the
      physiological role of cis-EODA in man.

PMID- 12505784
TI  - Analysis of biological samples by gas chromatography-mass spectrometry without a
      reference standard: measurement of urinary 18-hydroxytetrahydro-11
      dehydrocorticosterone excretion rate in human subjects.
AB  - Reference standards for some minor urinary steroid metabolites are sometimes
      unavailable. We describe a novel procedure to quantitate a urinary steroid
      metabolite of known structure and mass spectrum, using as a standard a compound
      which produces ions in common with it and has a similar retention time in gas
      chromatography-mass spectrometry. The steroid of interest was 18-hydroxy-11
      dehydrotetrahydrocorticosterone (18-OH-THA), the major urinary metabolite of 18
      hydroxycorticosterone (18-OH-B), a putative intermediate in the conversion of 11
      deoxycorticosterone to aldosterone. The steroid used as an alternative to the
      authentic 18-OH-THA standard was beta-cortol which, like 18-OH-THA, produces a
      fragmentation ion at m/z 457. Allo-tetrahydrodeoxycorticosterone (5alpha-THDOC)
      was used as the internal standard. beta-Cortolone also has the fragmentation ion
      at m/z 449 (in common with beta-cortol) and an authentic standard is available
      commercially. To validate the procedure, we quantitated beta-cortolone urinary
      excretion rate against this alternative standard and also against authentic beta
      cortolone standards. Both methods produced similar results (adjusted R(2): 0.998,
      P<0.001). The method was then used to measure urinary excretion of 18-OH-THA rate
      in healthy volunteers. The reference range obtained was 20-204 microgram/24 h
      (n=32). This is similar to the few results available by conventional assay.
      Method performance was also similar to other assays of urinary steroids. This
      procedure could be generally applicable for assays when authentic standards are
      not available but mass spectra are known or can be predicted.

PMID- 12505785
TI  - Improved enantioselective assay for the determination of fluoxetine and
      norfluoxetine enantiomers in human plasma by liquid chromatography.
AB  - A simple and innovative assay is described which allows the chiral separation of
      the four enantiomers of fluoxetine and norfluoxetine, with performance
      characteristics adequate for therapeutic drug monitoring. The assay requires
      liquid-liquid extraction into acetonitrile/n-hexane/isopropylic alcohol and re
      extraction into phosphoric acid for clean-up. The acidic layer is injected onto
      the HPLC system after filtering. Separation of the analytes is achieved with a
      Chiralcel ODR column and a mobile phase consisting of potassium
      hexafluorophosphate/acetonitrile. Detection is made by ultraviolet absorbance at
      227 nm. Standard curves are linear for each enantiomer (r(2)>/=0.992) over the
      range of 10-1000 ng/ml with a limit of quantification of 10 ng/ml for each
      enantiomer. Within-day and between-day CV% are </=10% for each enantiomer.

PMID- 12505786
TI  - One-second time resolution brain microdialysis in fully awake rats. Protocol for
      the collection, separation and sorting of nanoliter dialysate volumes.
AB  - Capillary zone electrophoresis is capable of analyzing nanoliter volumes,
      reducing the challenge posed by brain microdialysis time resolution improvement
      to the management of nanoliter dialysate volumes. This fact has not been
      overlooked and 12- and 6-s time resolution microdialysis have been reported in
      anesthetized rats. However, behavioral experiments require fully awake and freely
      moving animals. To achieve high temporal resolution brain microdialysis in awake
      unrestrained rats, we have developed an online device that mixes the outflowing
      dialysate with fluorescein isothiocyanate and buffer within a 26-nl reactor. The
      mixture was continuously accumulated in a 99-micrometer-bore capillary tube.
      After the experiment the tube was cut into 4-mm pieces and the content of each
      piece (30 nl, equivalent to 1 s dialysate) was transferred to a test tube. After
      allowing 18 h for derivatization, the samples were diluted with water and
      injected into a capillary electrophoresis laser-induced fluorescence detection
      instrument. This protocol was tested first in an in vitro assay and proved to be
      capable of detecting glutamate concentration changes in only 1 s. For the in vivo
      assays, a probe was inserted into the primary somatosensory cortex of eight rats
      divided in two groups. One group was stimulated by gently moving its whiskers for
      10 s. The other group had no whisker manipulation. Moving the whiskers released
      glutamate in the experimental group. The first and only change was observed at
      the 12th s. This method allows 1-s time resolution brain microdialysis in freely
      moving rats and multiple amino acid analysis every second during sensory
      perception or motor actions in behavioral experiments.

PMID- 12505787
TI  - Simultaneous measurement of plasma concentrations and 13C-enrichment of short
      chain fatty acids, lactic acid and ketone bodies by gas chromatography coupled to
      mass spectrometry.
AB  - A new method has been developed for the simultaneous measurement, in a reduced
      plasma sample, of concentration and 13C-isotopic enrichment of acetic, propionic,
      butyric, lactic, acetoacetic and beta-hydroxybutyric acids by gas chromatography
      coupled to mass spectrometry. After plasma deproteinisation, a diethylic
      extraction and a N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide
      derivatisation were performed. Both diethyl extraction and derivatisation
      procedures were optimised using the central composite designs methodology. The
      optimised method provides good linearity, intra-day and within-day repeatability.
      Except for beta-hydroxybutyric (49 microM) and acetoacetic acid (5 microM),
      detection limits were ranging between 0.2 and 0.7 microM allowing uses of this
      method for colonic metabolism studies.

PMID- 12505788
TI  - Automated determination of amisulpride by liquid chromatography with column
      switching and spectrophotometric detection.
AB  - A fully automated chromatographic method including on-line blood serum or plasma
      clean-up, isocratic high-performance liquid chromatography (HPLC) and
      spectrophotometric detection was developed for quantitative analysis of the new
      antipsychotic drug amisulpride. After injection of serum or plasma onto the HPLC
      system and clean-up on a pre-column (10x4.0 mm I.D.) filled with Silica CN 20
      micrometer (pore size 10 nm) by an eluent consisting of 8% acetonitrile in
      deionized water, the chromatographic separation was performed on Lichrospher CN
      (5 micrometer; 250x4.6 mm I.D.) by an eluent consisting of 50% acetonitrile and
      50% aqueous potassium phosphate buffer (0.008 M, pH 6.4). The UV detector was set
      at 254 nm. The limit of quantification was about 10 microgram/l. The method
      revealed linearity between 10 and 600 microgram/l (correlation coefficients
      R(2)>0.9996). The inter-assay reproducibility (coefficient of variation) of
      quality control samples was between 2.8 and 11.3%. Inaccuracy was between -0.6
      and +9.1%. The performance of daily calibration standards revealed an imprecision
      always below 15% and maximum inaccuracy of 7.7%. The method can be applied to
      therapeutic drug monitoring as well as pharmacokinetic studies of amisulpride.

PMID- 12505789
TI  - PAR1-dependent and independent increases in COX-2 and PGE2 in human colonic
      myofibroblasts stimulated by thrombin.
AB  - Subepithelial myofibroblast-derived prostaglandin E(2) (PGE(2)) regulates
      epithelial chloride secretion in the intestine. Thrombin is elevated in
      inflammatory conditions of the bowel. Therefore, we sought to determine a role
      for thrombin in regulating PGE(2) synthesis by colonic myofibroblasts. Incubation
      of cultured CCD-18Co colonic myofibroblasts with thrombin, the proteinase
      activated receptor 1 (PAR(1))-activating peptide (Cit-NH(2)), and peptides
      corresponding to 2 noncatalytic regions of thrombin (TP367 and TP508) for 18 h
      increased both cyclooxygenase (COX)-2 expression (immunocytochemistry) and PGE(2)
      synthesis (enzyme immunoassay). Inhibition of thrombin by D-Phe-Pro-Arg
      chloromethylketone (PPACK) did not significantly reduce PGE(2) synthesis, which
      remained elevated compared with control. We also investigated the basic
      fibroblast growth factor (bFGF) dependence of thrombin-induced PGE(2) elevations.
      Recombinant human bFGF concentration dependently increased PGE(2) synthesis, and
      a bFGF neutralizing antibody inhibited PGE(2) synthesis induced by TP367 and
      TP508 (approximately 40%) and by thrombin (approximately 20%) (but not Cit
      NH(2)). Thrombin, therefore, upregulates COX-2-derived PGE(2) synthesis by both
      catalytic cleavage of PAR(1) and bFGF-dependent noncatalytic activity. This
      presents a novel mechanism by which intestinal myofibroblasts might regulate
      epithelial chloride secretion.

PMID- 12505790
TI  - Interferon-gamma induces C/EBP beta expression and activity through MEK/ERK and
      p38 in T84 colon epithelial cells.
AB  - We investigated the role of IFN-gamma and MAPKs on the expression and activity of
      the transcription factor CCAAT/enhancer-binding protein-beta (C/EBP beta) in the
      T84 colon epithelial cell line. IFN-gamma induced the expression and activity of
      C/EBP beta and subsequently increased the secretion of IL-6 from these cells.
      Treatment with the p38 inhibitor SB-203580, the MEK1 and MEK2 inhibitor U-0126,
      or the translational inhibitor cycloheximide inhibited the induction of C/EBP
      beta and IL-6 by IFN-gamma, whereas the MEK1 inhibitor PD-98059 or the tyrosine
      kinase inhibitor genistein had no effect. These results suggest a role for MEK2
      and p38 in IFN-gamma-mediated signal transduction and induction of C/EBP beta
      expression and activity associated with interleukin-6 (IL-6) secretion in colon
      epithelial cells.

PMID- 12505791
TI  - Secretory activation of basolateral membrane Cl- channels in guinea pig distal
      colonic crypts.
AB  - Cell-attached recordings revealed Cl(-) channel activity in basolateral membrane
      of guinea pig distal colonic crypts isolated from basement membrane. Outwardly
      rectified currents ((gp)Cl(or)) were apparent with a single-channel conductance
      (gamma) of 29 pS at resting membrane electrical potential; another outward
      rectifier with gamma of 24 pS was also observed ( approximately 25% of
      (gp)Cl(or)). At a holding potential of -80 mV gamma was 18 pS for both (gp)Cl(or)
      currents, and at +80 mV gamma was 67 and 40 pS, respectively. Identity as Cl(-)
      channels was confirmed in excised patches by changing bath ion composition. From
      reversal potentials, relative permeability of K(+) over Cl(-) (P(K)/P(Cl)) was
      0.07 +/- 0.03, with relative permeability of Na(+) over Cl(-) (P(Na)/P(Cl)) =
      0.08 +/- 0.04. A second type of Cl(-) channel was seen with linear current
      voltage (I-V) relations ((gp)Cl(L)), having subtypes with gamma of 21, 13, and 8
      pS. Epinephrine or forskolin increased the number of open (gp)Cl(or) and
      (gp)Cl(L). Open probabilities (P(o)) of (gp)Cl(or), (gp)Cl(L21), and (gp)Cl(L13)
      were voltage dependent in cell-attached patches, higher at more positive
      potentials. Kinetics of (gp)Cl(or) were more rapid with epinephrine activation
      than with forskolin activation. Epinephrine increased P(o) at the resting
      membrane potential for (gp)Cl(L13). Secretagogue activation of these Cl(-)
      channels may contribute to stimulation of electrogenic K(+) secretion across
      colonic epithelium by increasing basolateral membrane Cl(-) conductance that
      permits Cl(-) exit after uptake via Na(+)-K(+)-2Cl(-) cotransport.

PMID- 12505792
TI  - Predisposition to addiction: pharmacokinetics, pharmacodynamics, and brain
      circuitry.

PMID- 12505793
TI  - Distinguishing between the validity and utility of psychiatric diagnoses.
AB  - OBJECTIVE: The meaning of the terms "validity" and "utility" as they apply to
      psychiatric diagnoses is examined. METHOD: The authors discuss the concepts of
      validity, utility, and disease; review assumptions that have been made about
      mental disorders as disease entities; and examine the evidence that mental
      disorders are separated from one another and from normality by natural boundaries
      (zones of rarity). RESULTS: Despite historical and recent assumptions to the
      contrary, there is little evidence that most currently recognized mental
      disorders are separated by natural boundaries. Researchers are increasingly
      assuming that variation in symptoms is continuous and are therefore questioning
      the validity of contemporary classifications. CONCLUSIONS: It is important to
      distinguish between validity and utility in considering psychiatric diagnoses.
      Diagnostic categories defined by their syndromes should be regarded as valid only
      if they have been shown to be discrete entities with natural boundaries that
      separate them from other disorders. Although most diagnostic concepts have not
      been shown to be valid in this sense, many possess high utility by virtue of the
      information about outcome, treatment response, and etiology that they convey.
      They are therefore invaluable working concepts for clinicians.

PMID- 12505794
TI  - Psychosis as a state of aberrant salience: a framework linking biology,
      phenomenology, and pharmacology in schizophrenia.
AB  - OBJECTIVE: The clinical hallmark of schizophrenia is psychosis. The objective of
      this overview is to link the neurobiology (brain), the phenomenological
      experience (mind), and pharmacological aspects of psychosis-in-schizophrenia into
      a unitary framework. METHOD: Current ideas regarding the neurobiology and
      phenomenology of psychosis and schizophrenia, the role of dopamine, and the
      mechanism of action of antipsychotic medication were integrated to develop this
      framework. RESULTS: A central role of dopamine is to mediate the "salience" of
      environmental events and internal representations. It is proposed that a
      dysregulated, hyperdopaminergic state, at a "brain" level of description and
      analysis, leads to an aberrant assignment of salience to the elements of one's
      experience, at a "mind" level. Delusions are a cognitive effort by the patient to
      make sense of these aberrantly salient experiences, whereas hallucinations
      reflect a direct experience of the aberrant salience of internal representations.
      Antipsychotics "dampen the salience" of these abnormal experiences and by doing
      so permit the resolution of symptoms. The antipsychotics do not erase the
      symptoms but provide the platform for a process of psychological resolution.
      However, if antipsychotic treatment is stopped, the dysregulated neurochemistry
      returns, the dormant ideas and experiences become reinvested with aberrant
      salience, and a relapse occurs. CONCLUSIONS: The article provides a heuristic
      framework for linking the psychological and biological in psychosis. Predictions
      of this hypothesis, particularly regarding the possibility of synergy between
      psychological and pharmacological therapies, are presented. The author describes
      how the hypothesis is complementary to other ideas about psychosis and also
      discusses its limitations.

PMID- 12505795
TI  - Depression, III: treatments.

PMID- 12505796
TI  - To comfort always.

PMID- 12505797
TI  - Patient reactions to a psychiatrist's pregnancy.

PMID- 12505798
TI  - Otto Rank, 1884-1939.

PMID- 12505799
TI  - Decision making in adolescents with behavior disorders and adults with substance
      abuse.
AB  - OBJECTIVE: The study assessed the validity of the Gambling Task as a test of
      decision-making ability in adolescents and examined whether adolescents with
      behavior disorders, who are at risk for substance abuse, have deficits in
      decision making similar to those exhibited by adults with substance abuse.
      METHOD: Performance on the Gambling Task in two testing sessions separated by 1
      week was assessed in 64 12-14-year-old adolescents (31 healthy, 33 with
      externalizing behavior disorders) and 52 adults (22 healthy, 30 with substance
      abuse). RESULTS: The healthy adolescents and the healthy adults had similar
      performance on the Gambling Task. Adolescents with behavior disorders performed
      more poorly than healthy adolescents, but only in the second testing session. In
      adults, overall Gambling Task performance did not differ between the healthy and
      substance abuse groups at either testing session, indicating no difference in
      learning of decision-making strategies between groups. However, adults with
      substance abuse performed more poorly than healthy adults during an early stage
      of the task, when participants presumably begin to understand the rewards and
      penalties involved in the task but are not yet sure of the actual risk of
      incurring penalities. CONCLUSIONS: The Gambling Task can be used with
      adolescents. Testing with the Gambling Task revealed a deficit in decision making
      in adolescents with behavior disorders, who are at risk for substance abuse. This
      deficit may represent a vulnerability factor for the development of substance
      abuse.

PMID- 12505800
TI  - Protective association of genetic variation in alcohol dehydrogenase with alcohol
      dependence in Native American Mission Indians.
AB  - OBJECTIVE: Two alcohol dehydrogenase genes (ADH2 and ADH3 on chromosome 4) and
      one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional
      polymorphisms. The goal of this study was to determine whether any associations
      exist between the ADH2, ADH3, and ALDH2 polymorphisms and alcohol dependence in a
      group of Native Americans. An additional goal was to determine if any
      associations exist between these polymorphisms and the endophenotype, maximum
      number of drinks ever consumed in a 24-hour period. METHOD: Mission Indian adults
      (N=340) were recruited for participation from reservations in southern
      California. Each participant completed an interview with the Semi-Structured
      Assessment for the Genetics of Alcoholism. A blood sample was collected from each
      participant for genotyping at the ALDH2, ADH2, and ADH3 loci. RESULTS: Sixty
      percent of all participants (72% of men and 53% of women) met lifetime DSM-III-R
      criteria for alcohol dependence. A significant difference in the ADH2 allele
      distributions was found between alcohol-dependent and non-alcohol-dependent
      participants. Those with alcohol dependence were significantly less likely to
      have the ADH2*3 allele (odds ratio=0.28) and significantly more likely to have
      the ADH2*1 allele (odds ratio=2.00) than those who were not alcohol dependent.
      Individuals with ADH2*3 reported a lower number of maximum drinks ever consumed
      in a 24-hour period, compared to those without this allele. CONCLUSIONS: These
      results are consistent with genetic linkage studies showing protective
      associations for alcohol dependence and related behavior on chromosome 4 and
      suggest that ADH2 polymorphisms may account for these findings. These results
      also highlight the utility of evaluating protective factors in populations with
      high rates of alcohol dependence.

PMID- 12505801
TI  - Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine
      users.
AB  - OBJECTIVE: The hypothesis that human cocaine users lose vesicular monoamine
      transporter (VMAT2) protein was tested in striatal samples from cocaine users and
      age-, sex-, and postmortem interval-matched comparison subjects. METHOD: Striatal
      samples were retrieved at autopsy; immunoblot assays were then performed by using
      a highly specific VMAT2 antibody. Striatal radioligand binding to VMAT2 was
      assessed with dihydrotetrabenazine ([(3)H]DTBZ) and dopamine levels employing
      high-performance liquid chromatography. RESULTS: Cocaine users displayed a marked
      reduction in VMAT2 immunoreactivity as well as reduced [(3)H]DTBZ binding and
      dopamine levels. It did not appear that the reduction in VMAT2 immunoreactivity
      was related to ethanol use, but dopamine levels were lower in subjects with only
      ethanol diagnoses. Subjects suffering from cocaine-induced mood disorders
      displayed a greater loss of VMAT2 immunoreactivity that approached significance.
      CONCLUSIONS: Human cocaine users lose VMAT2 protein, which might reflect damage
      to striatal dopamine fibers. These neuronal changes could play a role in causing
      disordered mood and motivational processes in more severely dependent patients.

PMID- 12505802
TI  - Predictors and correlates of suicide attempts over 5 years in 1,237 alcohol
      dependent men and women.
AB  - OBJECTIVE: In previous studies, factors related to a history of suicide attempts
      in persons with alcohol dependence have included sociodemographic variables, a
      more severe course of alcoholism, additional substance use disorders, and
      psychiatric comorbidity. This 5-year prospective study evaluated attributes
      associated with suicide attempts in a group of treatment-seeking persons with
      alcohol dependence. Psychiatric comorbidity was examined in terms of a
      distinction between substance-induced and independent psychiatric disorders.
      METHOD: Semistructured interviews were conducted with 1,237 alcohol-dependent
      subjects from the Collaborative Study on the Genetics of Alcoholism both at an
      initial evaluation and at a 5-year follow-up. Clinically relevant information was
      gathered at baseline, and suicidal behavior, aspects of alcohol dependence, and
      drug use were evaluated at the follow-up interview. RESULTS: Alcohol-dependent
      subjects (N=56) with suicide attempts during the follow-up period were more
      likely than subjects with no suicide attempts (N=1,181) to have made prior
      attempts. Other factors related to future suicide attempts in univariate analyses
      included younger age, being separated or divorced, other drug dependence,
      substance-induced psychiatric disorders, and indicators of a more severe course
      of alcoholism. Gender did not predict future attempts. CONCLUSIONS: A 5-year
      prospective evaluation of attributes associated with suicide attempts among
      alcohol-dependent persons identified factors that contributed to a small but
      significant proportion of the variance for future suicidal behavior.

PMID- 12505803
TI  - The neural substrates of affective processing in depressed patients treated with
      venlafaxine.
AB  - OBJECTIVE: The purpose of this study was to use functional magnetic resonance
      imaging (fMRI) to probe the neural circuitry associated with reactivity to
      negative and positive affective stimuli in patients with major depressive
      disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine.
      Relations between baseline neural activation and response to treatment were also
      evaluated. METHOD: Patients with major depressive disorder (N=12) and healthy
      comparison subjects (N=5) were scanned on three occasions, during which trials of
      alternating blocks of affective and neutral pictorial visual stimuli were
      presented. Symptoms were evaluated at each testing occasion, and both groups
      completed self-report measures of mood. Statistical parametric mapping was used
      to examine the fMRI data with a focus on the group-by-time interactions. RESULTS:
      Patients showed a significant reduction in depressive symptoms with treatment.
      Group-by-time interactions in response to the negative versus neutral stimuli
      were found in the left insular cortex and the left anterior cingulate. At
      baseline, both groups showed bilateral activation in the visual cortices, lateral
      prefrontal cortex, and amygdala in response to the negative versus neutral
      stimuli, with patients showing greater activation in the visual cortex and less
      activation in the left lateral prefrontal cortex. Patients with greater relative
      anterior cingulate activation at baseline in response to the negative versus
      neutral stimuli showed the most robust treatment response. CONCLUSIONS: The
      findings underscore the importance of the neural circuitry activated by negative
      affect in depression and indicate that components of this circuitry can be
      changed within 2 weeks of treatment with antidepressant medication.

PMID- 12505804
TI  - Response of cortical metabolic deficits to serotonergic challenge in familial
      mood disorders.
AB  - OBJECTIVE: In subjects with mood disorders, positron emission tomography (PET)
      with [(18)F]fluorodeoxyglucose has shown prefrontal cortical metabolism deficits,
      including in a subgenual region in subjects with familial illness. The authors
      applied a dl-fenfluramine challenge method to study metabolic response in this
      region to serotonergic challenge in familial major depression. METHOD: The study
      group consisted of 19 depressed subjects with major depressive disorder or
      bipolar disorder, all of whom had at least one first-degree relative with history
      of major depression, and 10 healthy volunteers with similar age and gender
      distributions. PET images were acquired under placebo and challenge conditions,
      and volumetric MRI scans were also obtained. Group comparisons of metabolic and
      volumetric data were performed. Ratings of acute mood change during serotonergic
      challenge were compared with the imaging data. RESULTS: Within Brodmann's area
      32, a glucose metabolism deficit in the depressed subjects on placebo day was
      observed by voxel-level analysis, but no volumetric deficit was found in the
      subgenual regions examined. Under challenge, both groups suppressed metabolism
      similarly. Within the patient group, the correlation between acute mood
      improvement during challenge and greater metabolic suppression approached
      significance. CONCLUSIONS: In familial mood disorders, a ventromedial prefrontal
      cortical deficit in baseline metabolism is not due to altered structural volume,
      and the response to serotonergic challenge appears predictive of acute mood
      response. The potential to predict treatment response can be tested by a combined
      challenge and treatment study.

PMID- 12505805
TI  - High-dimensional mapping of the hippocampus in depression.
AB  - OBJECTIVE: Abnormalities of the hippocampus may play a role in the
      pathophysiology of depression, but efforts to identify a structural abnormality
      in this brain structure among depressed patients have produced mixed results.
      Previous research may have been limited by exclusive reliance on measures of
      hippocampal volume. High-dimensional brain mapping is a new analytic method that
      quantitatively characterizes the shape as well as volume of a brain structure. In
      this study, high-dimensional brain mapping was used to evaluate hippocampal shape
      and volume in patients with major depressive disorder and healthy comparison
      subjects. METHOD: By using magnetic resonance imaging, brain scans were obtained
      from 27 patients with major depressive disorder and 42 healthy comparison
      subjects. High-dimensional brain mapping generated a series of 10 variables
      (components) that represented hippocampal shape, and hippocampal volumes were
      also computed. Analysis of variance techniques were used to compare depressed
      patients and comparison subjects on hippocampal shape and volume. RESULTS: While
      the depressed patients and comparison subjects did not differ in hippocampal
      volume, there were highly significant group differences in hippocampal shape. The
      two groups did not overlap on a discriminant function computed from a model
      comprising the 10 components. The pattern of hippocampal surface deformation in
      the depressed patients suggested specific involvement of the subiculum.
      CONCLUSIONS: Patients with major depression may have structural abnormalities of
      the hippocampus that can be detected by analysis of hippocampal shape but not
      volume. A specific defect in the subiculum could have widespread effects
      throughout neurocircuits that appear to be abnormal in depression.

PMID- 12505806
TI  - Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.
AB  - OBJECTIVE: Dysfunctional attitudes are negatively biased assumptions and beliefs
      regarding oneself, the world, and the future. In healthy subjects, increasing
      serotonin (5-HT) agonism with a single dose of d-fenfluramine lowered
      dysfunctional attitudes. To investigate whether the converse, a low level of 5-HT
      agonism, could account for the higher levels of dysfunctional attitudes observed
      in patients with major depression or with self-injurious behavior, cortex 5-HT(2)
      receptor binding potential and dysfunctional attitudes were measured in patients
      with major depressive disorder, patients with a history of self-injurious
      behavior, and healthy comparison subjects (5-HT(2) receptor density increases
      during 5-HT depletion). METHOD: Twenty-nine healthy subjects were recruited to
      evaluate the effect of d-fenfluramine or of clonidine (control condition) on
      dysfunctional attitudes. Dysfunctional attitudes were assessed with the
      Dysfunctional Attitude Scale 1 hour before and 1 hour after drug administration.
      In a second experiment, dysfunctional attitudes and 5-HT(2) binding potential
      were measured in 22 patients with a major depressive episode secondary to major
      depressive disorder, 18 patients with a history of self-injurious behavior
      occurring outside of a depressive episode, and another 29 age-matched healthy
      subjects. Cortex 5-HT(2) binding potential was measured with [(18)F]setoperone
      positron emission tomography. RESULTS: In the first experiment, dysfunctional
      attitudes decreased after administration of d-fenfluramine. In the second
      experiment, in the depressed group, dysfunctional attitudes were positively
      associated with cortex 5-HT(2) binding potential, especially in Brodmann's area 9
      (after adjustment for age). Depressed subjects with extremely dysfunctional
      attitudes had higher 5-HT(2) binding potential, compared to healthy subjects,
      particularly in Brodmann's area 9. CONCLUSIONS: Low levels of 5-HT agonism in the
      brain cortex may explain the severely pessimistic, dysfunctional attitudes
      associated with major depression.

PMID- 12505807
TI  - Mathematics deficits in adolescents with bipolar I disorder.
AB  - OBJECTIVE: This study examined mathematical ability in adolescents with bipolar I
      disorder, compared to adolescents with major depressive disorder and
      psychiatrically healthy comparison subjects. METHOD: Participants (N=119)
      included adolescents in remission from bipolar disorder (N=44) or major
      depressive disorder (N=30), as well as comparison subjects (N=45) with no
      psychiatric history. Participants were assessed with the following measures: the
      Wide-Range Achievement Test, Revised 2 (WRAT-R2), Peabody Individual Achievement
      Test, Bay Area Functional Performance Evaluation Task-Oriented Assessment
      (functional mathematics subtest), Test of Nonverbal Intellegence-2, and a self
      report of mathematics performance. RESULTS: WRAT-R2 and Peabody Individual
      Achievement Test scores for spelling, mathematics, and reading revealed that
      adolescents with bipolar disorder had significantly lower achievement in
      mathematics, compared to subjects with major depressive disorder and comparison
      subjects. Results for the Test of Nonverbal Intellegence-2 were not significantly
      different between groups. Adolescents with bipolar disorder took significantly
      longer to complete the Bay Area Functional Performance Evaluation mathematics
      task. Significantly fewer adolescents with bipolar disorder (9%) reported above
      average mathematics performance, compared with the other groups. CONCLUSIONS:
      Adolescents with remitted bipolar disorder have a specific profile of mathematics
      difficulties that differentiates them from both adolescents with unipolar
      depression and psychiatrically healthy comparison subjects. These mathematics
      deficits may not derive simply from more global deficits in nonverbal
      intelligence or executive functioning, but may be associated with neuroanatomical
      abnormalities that result in cognitive deficits, including a slowed response
      time. These deficits suggest the need for specialized assessment of mathematics
      as part of a comprehensive clinical follow-up treatment plan.

PMID- 12505808
TI  - Testosterone gel supplementation for men with refractory depression: a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: Testosterone supplementation may produce antidepressant effects in
      men, but until recently it has required cumbersome parenteral administration. In
      an 8-week randomized, placebo-controlled trial, the authors administered a
      testosterone transdermal gel to men aged 30-65 who had refractory depression and
      low or borderline testosterone levels. METHOD: Of 56 men screened, 24 (42.9%)
      displayed morning serum total testosterone levels of 350 ng/dl or less (normal
      range=270-1070). Of these men, 23 entered the study. One responded to an initial
      1-week single-blind placebo period, and 22 were subsequently randomly assigned:
      12 to 1% testosterone gel, 10 g/day, and 10 to identical-appearing placebo. Each
      subject continued his existing antidepressant regimen. Ten subjects receiving
      testosterone and nine receiving placebo completed the 8-week trial. RESULTS: The
      groups were closely matched on baseline demographic and psychiatric measures.
      Subjects receiving testosterone gel had significantly greater improvement in
      scores on the Hamilton Depression Rating Scale than subjects receiving placebo.
      These changes were noted on both the vegetative and affective subscales of the
      Hamilton Depression Rating Scale. A significant difference was also found on the
      Clinical Global Impression severity scale but not the Beck Depression Inventory.
      One subject assigned to testosterone reported increased difficulty with
      urination, suggesting an exacerbation of benign prostatic hyperplasia; no other
      subject reported adverse events apparently attributable to testosterone.
      CONCLUSIONS: These preliminary findings suggest that testosterone gel may produce
      antidepressant effects in the large and probably underrecognized population of
      depressed men with low testosterone levels.

PMID- 12505809
TI  - Obesity as a correlate of outcome in patients with bipolar I disorder.
AB  - OBJECTIVE: This study sought to evaluate the relationship of obesity to
      demographic and clinical characteristics and treatment outcome in a group of 175
      patients with bipolar I disorder who were treated for an acute affective episode
      and followed through a period of maintenance treatment. METHOD: Data were from
      participants entering the Maintenance Therapies for Bipolar Disorder protocol
      between 1991 and 2000. Analyses focused on differences in baseline demographic
      and clinical characteristics and in treatment outcomes between obese and nonobese
      patients. RESULTS: A total of 35.4% of the patients met criteria for obesity.
      Significant differences between the obese and nonobese patients were observed for
      years of education, numbers of previous depressive and manic episodes, baseline
      scores on the Hamilton Rating Scale for Depression, and durations of the acute
      episode. A Kaplan-Meier survival analysis indicated a significantly shorter time
      to recurrence during the maintenance phase among obese patients. The number of
      patients experiencing a depressive recurrence was significantly higher in the
      obese than in the nonobese group. CONCLUSIONS: Obesity is correlated with a
      poorer outcome in patients with bipolar I disorder. Preventing and treating
      obesity in bipolar disorder patients could decrease the morbidity and mortality
      related to physical illness, enhance psychological well-being, and possibly
      improve the course of bipolar illness. Weight-control interventions specifically
      designed for patients with bipolar illness should be developed, tested, and
      integrated into the routine care provided for these patients.

PMID- 12505810
TI  - In vivo determination of muscarinic acetylcholine receptor availability in
      schizophrenia.
AB  - OBJECTIVE: Postmortem studies have implicated the central muscarinic
      acetylcholine system in schizophrenia. However, central muscarinic receptor
      availability has not previously been studied in vivo. Using [I
      123]iodoquinuclidinyl benzilate ([(123)I]IQNB) single photon emission computed
      tomography (SPECT), the authors sought to compare the muscarinic receptor
      availability in vivo in unmedicated patients with schizophrenia and normal
      subjects. METHOD: Twelve medication-free patients with schizophrenia underwent an
      [(123)I]IQNB SPECT scan during approximate-equilibrium conditions. A group of 10
      age- and gender-matched normal comparison subjects were given the same kind of
      scan under similar conditions. Regions of interest were analyzed in the cortex,
      basal ganglia, thalamus, and pons. Binding data were analyzed as nCi/ml tissue
      per mCi injected dose. RESULTS: Muscarinic receptor availability was
      significantly less in patients with schizophrenia than in normal subjects in all
      regions of interest except the pons. Reductions ranged from -33% in the caudate
      to -20% in the occipital cortex. Positive symptoms of schizophrenia correlated
      negatively with muscarinic receptor availability in the striatum and the frontal
      cortex. CONCLUSIONS: These results indicate a reduction in muscarinic
      acetylcholine receptor availability in vivo in unmedicated patients with
      schizophrenia, confirming results from postmortem studies and adding further
      evidence that the muscarinic system is involved in the pathophysiology of
      schizophrenia.

PMID- 12505811
TI  - Progressive loss of cerebellar volume in childhood-onset schizophrenia.
AB  - OBJECTIVE: Childhood-onset schizophrenia is a severe and unremitting form of the
      disorder. Prospective brain magnetic resonance imaging (MRI) studies have found
      progressive loss of total cerebral volume during adolescence, primarily
      attributable to accelerated loss of cortical gray matter. Because there is
      evidence of cerebellar involvement in schizophrenia, the authors examined
      cerebellar volume and its relation to cortical gray matter development during
      adolescence in patients with childhood-onset schizophrenia and healthy comparison
      subjects. METHOD: Total cerebellar volume was algorithmically calculated for 108
      anatomical brain MRI scans from 50 patients (20 of whom were female) and 101
      scans from 50 age- and gender-matched healthy volunteers (20 of whom were
      female). The age range of the patients and comparison subjects was 8 to 24.
      Midsagittal vermal area and posterior-inferior vermal lobe volume were measured
      by hand. Prospective rescans were obtained at approximately 2-year intervals.
      Cross-sectional and longitudinal data were combined in mixed model regressions to
      compare developmental changes for the groups. RESULTS: In contrast to healthy
      volunteers, patients with schizophrenia showed a progressive loss of cerebellar
      volume during adolescence. Cerebellar and cerebral volume decreases were
      significantly correlated in childhood-onset schizophrenia. CONCLUSIONS: Childhood
      onset schizophrenia is associated with significant progressive loss of cerebellar
      volume during adolescence, consistent with previously reported decreases in total
      cerebral and cortical gray matter. At least in these patients with severe early
      onset schizophrenia, the loss appears secondary to a generalized process.

PMID- 12505812
TI  - Abnormal sequencing of motor actions in patients with schizophrenia: evidence
      from grip force adjustments during object manipulation.
AB  - OBJECTIVE: During object manipulation, grip force must be adjusted in
      anticipation of destabilizing load forces to prevent the object from slipping.
      This study used three gripping tasks to assess whether schizophrenia affects the
      predictive mechanisms required for the scaling, timing, and/or sequencing of
      motor actions. METHOD: Sixteen patients with schizophrenia and 16 comparison
      subjects matched for age, sex, and educational level 1) lifted objects of various
      mass and texture (lift task) and 2) used a manipulandum to hit (hit task) or
      resist (resist task) impacts produced by a collision with a pendulum. For an
      optimized performance, all tasks demanded a predictive increase in grip force and
      the timing of external events. The fluid sequencing of finger and hand
      submovements was required for the lift and the hit tasks but not for the resist
      task. RESULTS: Patients were impaired in the smooth execution of both the lift
      and the hit tasks but not in the performance of the resist task. In all three
      tasks, the scaling of grip force was similar for patients and comparison
      subjects. CONCLUSIONS: Schizophrenia is associated with a specific deficit in the
      sequencing of motor actions rather than with an overall problem in the predictive
      control of movement.

PMID- 12505813
TI  - Untreated initial psychosis: relation to cognitive deficits and brain morphology
      in first-episode schizophrenia.
AB  - OBJECTIVE: Studies of patients experiencing their first episode of psychosis have
      demonstrated that they typically remain undiagnosed and untreated for 1-2 years.
      It has been postulated that prolonged untreated psychosis may have serious
      effects: poor response to neuroleptic medications, poor clinical outcomes, and
      direct neurotoxicity. This study investigated the relationships between duration
      of untreated initial psychosis and neurocognitive functioning and high-resolution
      imaging brain measurements. METHOD: A total of 156 subjects with DSM-IV
      schizophrenia, schizophreniform disorder, or schizoaffective disorder were
      evaluated during their first episode of psychosis. Measurements included nine
      domains of neurocognitive functioning, volumetric measures of total brain tissue,
      gray and white matter, and CSF, and measures of brain surface anatomy. RESULTS:
      The mean duration of untreated initial psychosis was 74.3 weeks. Correlations
      between neurocognitive functioning, brain volumetric measurements, and surface
      anatomy measurements with duration of untreated initial psychosis were weak; none
      reached statistical significance. When the group was divided on the basis of
      median duration of untreated initial psychosis, there were again no significant
      differences between the groups with long and short duration of untreated initial
      psychosis except on two measures (verbal memory and cortical sulcal depth).
      CONCLUSIONS: The absence of strong correlations suggests that untreated initial
      psychosis has no direct toxic neural effects. These results suggest that large
      scale initiatives designed to prevent neural injury through early intervention in
      the prepsychotic or early psychosis phase may be based on incorrect assumptions
      that neurotoxicity or cognitive deterioration may be avoided. Nevertheless, early
      treatment is justified because it reduces suffering.

PMID- 12505814
TI  - Distribution of microtubule-associated protein MAP2-immunoreactive interstitial
      neurons in the parahippocampal white matter in subjects with schizophrenia.
AB  - OBJECTIVE: Evidence suggests that schizophrenia is a neurodevelopmental disorder
      that may involve abnormal connectivity between various cortical and subcortical
      brain areas. The parahippocampal gyrus is an area important for higher cognition
      in which a variety of cytoarchitectural, neuronal morphometric, and innervation
      abnormalities in schizophrenia have been reported. Previous studies have reported
      abnormal distributions of interstitial white matter neurons in prefrontal,
      parietal, and temporal neocortices, which suggests that schizophrenia may be
      related to prenatal disturbances in the cortical subplate, a transitory structure
      involved in the formation of connections in the developing cortex from which the
      interstitial white matter neurons derive. Abnormalities in the distribution of
      interstitial white matter neurons in the parahippocampal gyrus in schizophrenia
      may indicate an alteration in the migration of subplate neurons or in the pattern
      of programmed cell death that could lead to defective cortical circuitry and
      impaired cognition. METHOD: The authors used a monoclonal antibody against the
      microtubule-associated protein MAP2 to label interstitial white matter neurons in
      the anterior region of the parahippocampal gyrus from 41 individuals with
      schizophrenia and 15 comparison subjects. The distribution of MAP2-labeled
      neurons in relation to the gray matter/white matter boundary was determined by
      computer-assisted microscopy. RESULTS: The number of interstitial white matter
      neurons decreased with increasing white matter depth in both groups, but
      significantly more slowly in the schizophrenia group, with interstitial white
      matter neurons located deeper in white matter in schizophrenia subjects.
      CONCLUSIONS: These findings indicate there is an abnormality in the residua of
      the cortical subplate in the anterior region of the adult parahippocampal gyrus
      in schizophrenia subjects.

PMID- 12505815
TI  - Progressive decrease of left superior temporal gyrus gray matter volume in
      patients with first-episode schizophrenia.
AB  - OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left
      superior temporal gyrus, have been reported in magnetic resonance imaging (MRI)
      studies of patients with chronic schizophrenia and, more recently, in patients
      with first-episode schizophrenia. However, it remains unknown whether there are
      progressive decreases in temporal lobe cortical gray matter volumes in patients
      with first-episode schizophrenia and whether similarly progressive volume
      decreases are present in patients with affective psychosis. METHOD: High-spatial
      resolution MRI scans at initial hospitalization and 1.5 years later were obtained
      from 13 patients with first-episode schizophrenia, 15 patients with first-episode
      affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI
      volumes were calculated for gray matter of superior temporal gyrus and for the
      amygdala-hippocampal complex. RESULTS: Patients with first-episode schizophrenia
      showed significant decreases in gray matter volume over time in the left superior
      temporal gyrus compared with patients with first-episode affective psychosis or
      healthy comparison subjects. This progressive decrease was more pronounced in the
      posterior portion of the left superior temporal gyrus (mean=9.6%) than in the
      anterior portions (mean=8.4%). No group differences in the rate of change over
      time were present in other regions. CONCLUSIONS: These findings demonstrate a
      progressive volume reduction of the left posterior superior temporal gyrus gray
      matter in patients with first-episode schizophrenia but not in patients with
      first-episode affective psychosis.

PMID- 12505816
TI  - Diminished impulsivity in older patients with borderline personality disorder.
AB  - OBJECTIVE: The aim of this study was to test, in terms of impulsivity, the
      hypothesis that borderline personality disorder "burns out" with age. METHOD:
      Linear regression analyses, with age as a predictor variable, were conducted on
      subsection scores of the Revised Diagnostic Interview for Borderlines (DIB-R) for
      123 individuals with a diagnosis of borderline personality disorder who were
      accepted into an outpatient-based psychotherapy program. The subsection scores of
      the DIB-R allow quantification of the core features of the disorder: affective
      disturbance, relationship disturbance, cognitive disturbance, and impulsive
      behavior. RESULTS: Older patients with borderline personality disorder showed
      less impulsivity than younger patients, but there was no difference in terms of
      affect disturbance, identity disturbance, and interpersonal problems.
      CONCLUSIONS: The view that borderline personality disorder burns out with age is
      supported in terms of impulsivity.

PMID- 12505817
TI  - omega-3 Fatty acid treatment of women with borderline personality disorder: a
      double-blind, placebo-controlled pilot study.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of ethyl
      eicosapentaenoic acid (E-EPA) and placebo in the treatment of female subjects
      with borderline personality disorder. METHOD: The authors conducted an 8-week,
      placebo-controlled, double-blind study of E-EPA in 30 female subjects meeting
      Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline
      personality disorder. RESULTS: Twenty subjects were randomly assigned to 1 g of E
      EPA; 10 subjects were given placebo. Ninety percent of those in both groups
      completed all 8 weeks of the trial. Analyses that used random-effects regression
      modeling and controlled for baseline severity showed E-EPA to be superior to
      placebo in diminishing aggression as well as the severity of depressive symptoms.
      CONCLUSIONS: The results of this study suggest that E-EPA may be a safe and
      effective form of monotherapy for women with moderately severe borderline
      personality disorder.

PMID- 12505818
TI  - Health service utilization costs for borderline personality disorder patients
      treated with psychoanalytically oriented partial hospitalization versus general
      psychiatric care.
AB  - OBJECTIVE: The authors assessed health care costs associated with
      psychoanalytically oriented partial hospital treatment for borderline personality
      disorder compared with treatment as usual within general psychiatric services.
      METHOD: Health care utilization of all borderline personality disorder patients
      who participated in a previous trial of partial hospital treatment compared with
      treatment as usual was assessed by using information from case notes and service
      providers. Costs were compared for the 6 months before treatment, 18 months of
      treatment, and an 18-month follow-up period. RESULTS: There were no cost
      differences between the groups during pretreatment or treatment. Costs of partial
      hospital treatment were offset by less psychiatric inpatient care and reduced
      emergency room treatment. The trend for costs to decrease in the partial
      hospitalization group during the follow-up period was not apparent in the
      treatment-as-usual group. CONCLUSIONS: Specialist partial hospital treatment for
      borderline personality disorder is no more expensive than treatment as usual and
      shows considerable cost savings after treatment.

PMID- 12505819
TI  - Prevalence of hepatitis C among psychiatric patients in the public sector.
AB  - OBJECTIVE: This study estimated the seroprevalence of hepatitis C virus in a
      public-sector psychiatric hospital. METHOD: Patients admitted between Jan. 1,
      1998, and Dec. 30, 2000, were routinely screened for hepatitis C virus antibody
      on admission. RESULTS: A total of 133 (8.5%) of 1,556 patients admitted were
      positive for the hepatitis C virus. Aminotransferase levels were elevated but
      rarely abnormal among patients positive for the hepatitis C virus. Hepatitis B
      surface antibody was found in 27.8% of the patients positive for the hepatitis C
      virus. These patients were more likely to receive a diagnosis of psychoactive
      substance use disorder but no other psychiatric diagnoses. CONCLUSIONS: The
      prevalence of hepatitis C virus is high among psychiatric patients in the public
      sector. Much needs to be learned about the role of universal screening and
      effective techniques for primary prevention and antiviral treatment in this
      population.

PMID- 12505820
TI  - The safety of valproic acid use for patients with hepatitis C infection.
AB  - OBJECTIVE: Valproic acid is frequently not recommended for patients with hepatic
      dysfunction. The authors evaluated the association between hepatitis C and
      alanine aminotransferase (ALT) values during valproic acid treatment. METHOD: ALT
      changes in 564 individuals beginning valproic acid treatment were examined.
      Changes among those with positive hepatitis C status were compared with changes
      among patients with positive hepatitis C status who were taking other
      psychotropic agents. RESULTS: ALT elevations with valproic acid were
      significantly greater among patients with positive hepatitis C status than those
      with negative or unknown status. Among patients with positive hepatitis C status,
      ALT increases did not differ significantly between valproic acid and other
      medications. CONCLUSIONS: Use of valproic acid may be possible for some patients
      with hepatitis C. ALT increases in seropositive patients may be partially related
      to chronic hepatitis infection. However, ALT levels should be closely monitored
      in all hepatitis C patients taking valproic acid.

PMID- 12505821
TI  - Validity of the mood disorder questionnaire: a general population study.
AB  - OBJECTIVE: This study tested the validity in the adult general population of the
      Mood Disorder Questionnaire, a screening instrument for bipolar I and II
      disorders. The Mood Disorder Questionnaire has been validated in a psychiatric
      outpatient study group. METHOD: A total of 711 subjects (stratified by Mood
      Disorder Questionnaire score) were randomly selected from a group of 85,358 adult
      respondents in a nationwide epidemiological general population sample that was
      balanced for key demographic variables. Of these, 695 subjects received a
      telephone interview involving an abbreviated version of the Structured Clinical
      Interview for DSM-IV. RESULTS: A sensitivity of 0.281 and a specificity of 0.972
      were obtained for the Mood Disorder Questionnaire. CONCLUSIONS: The Mood Disorder
      Questionnaire is a useful screening instrument for bipolar I and II disorders in
      the community. The operating characteristics of the Mood Disorder Questionnaire
      in the general population differ substantially from its characteristics in
      outpatient psychiatric settings.

PMID- 12505822
TI  - Reliability, validity, and classification accuracy of a measure of DSM-IV
      diagnostic criteria for pathological gambling.
AB  - OBJECTIVE: The purpose of this study was to measure the reliability, validity,
      and classification accuracy of the DSM-IV diagnostic criteria for pathological
      gambling. METHOD: Participants in this study were drawn from two sources: 803 men
      and women from the general adult population of Minnesota and 259 men and women
      who were admitted to a gambling treatment program. A 19-item measure of the DSM
      IV diagnostic criteria for pathological gambling was administered, along with
      other validity measures. RESULTS: The DSM-IV diagnostic criteria were found to be
      reliable and valid. With a standard cutoff score of 5, DSM-IV criteria yielded
      satisfactory classification accuracy results; however, a cutoff score of 4 made
      modest improvements in classification accuracy and, most important, reduced the
      rate of false negatives. CONCLUSIONS: The DSM-IV diagnostic criteria for
      pathological gambling, when operationalized into questions, demonstrated
      satisfactory reliability, validity, and classification accuracy, and a cutoff
      score of 4 improved diagnostic precision.

PMID- 12505823
TI  - Hypomania induced by adjunctive lamotrigine.

PMID- 12505824
TI  - Dexamphetamine for obsessive-compulsive disorder.

PMID- 12505825
TI  - Bipolar disorder with Asperger's disorder.

PMID- 12505826
TI  - Clozapine and postmortem redistribution.

PMID- 12505827
TI  - Biopsychosocial psychiatry.

PMID- 12505828
TI  - Biopsychosocial psychiatry.

PMID- 12505830
TI  - Controlled trials of psychotherapy.

PMID- 12505831
TI  - Biopsychosocial psychiatry.

PMID- 12505833
TI  - omega-3 Fatty acid for schizophrenia.

PMID- 12505834
TI  - Underuse of antidepressants.

PMID- 12505837
TI  - Problems with odds ratios.

PMID- 12505839
TI  - Consolidated standard of reporting trials guidelines.

PMID- 12505840
TI  - Problems with odds ratios.

PMID- 12505858
TI  - Autonomic modulation of heart rate during obstructive versus central apneas in
      patients with sleep-disordered breathing.
AB  - Sleep-disordered breathing is associated with an altered sympathovagal balance
      determined by the nocturnal cyclic alternating of apneas and hyperventilation.
      The aim of this study was to determine whether the autonomic modulation of heart
      rate during obstructive apneas (OA) and central apneas (CA) in patients with
      sleep-disordered breathing is different. Therefore, by using the time-varying
      Wigner-Ville transform spectral analysis we described, in 17 patients, the time
      course of the low-frequency (LF) and the high-frequency (HF) components of the
      interbeat interval (R-R interval) reflecting, at large, respectively, the
      sympathetic and the parasympathetic modulation, during OA (n = 185) and CA (n =
      51) and during the postapneic hyperventilation. In both types of apneas we found
      cyclic lengthening/shortening in R-R interval, during apneas/postapneic
      hyperventilation, respectively, with more marked bradycardia during OA (R-R:
      1,011 +/- 23 versus 893 +/- 30 ms2, p < 0.01). In OA the HF oscillations
      decreased from the apnea to the postapneic hyperventilation (from 1,964 +/- 244
      to 387 +/- 98 ms2, p < 0.0001), whereas the LF oscillations increased (from 2,649
      +/- 230 to 9,820 +/- 716 ms2, p < 0.0001). Conversely, in CA the HF oscillations
      increased from the apnea to the postapneic hyperventilation (from 452 +/- 177 to
      1,485 +/- 406 ms2, p < 0.0001), whereas the LF component remained unchanged.
      These results show markedly different autonomic alterations during and after OA
      versus CA, suggesting a surge in sympathetic modulation after the obstructive
      episodes.

PMID- 12505859
TI  - Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized
      trial.
AB  - Pulmonary rehabilitation is beneficial for patients with chronic lung disease.
      However, long-term maintenance has been difficult to achieve after short-term
      treatment. We evaluated a telephone-based maintenance program after pulmonary
      rehabilitation in 172 patients with chronic lung disease recruited from pulmonary
      rehabilitation graduates. Subjects were randomly assigned to a 12-month
      maintenance intervention with weekly telephone contacts and monthly supervised
      reinforcement sessions (n = 87) or standard care (n = 85) and followed for 24
      months. Except for a slight imbalance between sexes, experimental and control
      groups were equivalent at baseline and showed similar improvements after
      rehabilitation. During the 12-month intervention, exercise tolerance (maximum
      treadmill workload and 6-minute walk distance) and overall health status ratings
      were better maintained in the experimental group together with a reduction in
      hospital days. There were no group differences for other measures of pulmonary
      function, dyspnea, self-efficacy, generic and disease-specific quality of life,
      and health care use. By 24 months, there were no significant group differences.
      Patients returned to levels close to but above prerehabilitation measures. We
      conclude that a maintenance program of weekly telephone calls and monthly
      supervised sessions produced only modest improvements in the maintenance of
      benefits after pulmonary rehabilitation.

PMID- 12505860
TI  - Imaging pulmonary gene expression with positron emission tomography.
AB  - We evaluated positron emission tomographic imaging of pulmonary transgene
      expression, using an enhanced mutant herpes simplex virus-1 thymidine kinase as
      the reporter gene, in the lungs of normal rats. Sixteen rats were studied 3 days
      after an intratracheal administration of 5 x 10(9) to 1 x 10(11) viral particles
      of a replication-incompetent adenovirus containing a fusion gene of the mutant
      kinase and green fluorescent protein. Three rats infected with adenovirus
      containing no insert (null vector) served as control subjects. Images were
      obtained 1 hour after an intravenous injection of 9-(4-[18F]-fluoro-3
      hydroxymethylbutyl)guanine, an imaging substrate for the viral kinase. After
      euthanasia, tissue radioactivity was determined in a gamma counter, and thymidine
      kinase activity and green fluorescent protein levels were measured in lung tissue
      samples. Imaging and gamma counting radioactivity measurements were strongly and
      linearly correlated (r2 = 0.96, p < 0.001). Imaging detected thymidine kinase
      expression above background (null vector) in 15 of 16 rats, even at low viral
      doses that produced little to no measurable green fluorescent protein expression.
      Lung 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine uptake (as assessed by
      imaging) correlated with in vitro assays of both kinase activity (r(2) = 0.48, p
      < 0.001) and fluorescent protein (r(2) = 0.46, p < 0.001). We conclude that
      positron emission tomographic imaging is a sensitive and quantitative method for
      detecting pulmonary reporter gene expression noninvasively.

PMID- 12505861
TI  - Cycloheximide increases glucocorticoid-stimulated alpha -ENaC mRNA in collecting
      duct cells by p38 MAPK-dependent pathway.
AB  - Aldosterone and glucocorticoids (GCs) stimulate Na(+) reabsorption in the
      collecting ducts by increasing the activity of the epithelial Na(+) channel
      (ENaC). Our laboratory has used Madin-Darby canine kidney-C7 cells to demonstrate
      that this effect is associated with an increase in alpha-ENaC gene transcription
      (Mick VE, Itani OA, Loftus RW, Husted RF, Schmidt TJ, and Thomas CP, Mol
      Endocrinol 15: 575-588, 2001). Cycloheximide (CHX) superinduced the GC-stimulated
      alpha-ENaC expression in a dose-dependent manner, but had no effect on basal or
      aldosterone-stimulated alpha-ENaC expression, whereas anisomycin inhibited basal
      and corticosteroid-stimulated alpha-ENaC expression. The superinduction of alpha
      ENaC expression was also seen with hypotonicity, was blocked by RU-38486, and was
      independent of protein synthesis. CHX had no effect on alpha-ENaC mRNA half-life,
      confirming that its effect was via an increase in alpha-ENaC transcription. The
      effect of CHX and hypotonicity on alpha-ENaC expression was abolished by SB
      202190, indicating an effect mediated via p38 MAPK. Consistent with this scheme,
      CHX increased pp38 and MKK6, an upstream activator of p38, stimulated alpha-ENaC
      promoter activity. These data confirm a model in which CHX activates p38 in Madin
      Darby canine kidney-C7 cells to increase alpha-ENaC gene transcription in a GC
      dependent manner.

PMID- 12505862
TI  - Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression
      during epithelial-mesenchymal transition.
AB  - New research suggests that, during tubulointerstitial fibrosis, alpha-smooth
      muscle actin (SMA)-expressing mesenchymal cells might derive from the tubular
      epithelium via epithelial-mesenchymal transition (EMT). Although transforming
      growth factor-beta(1) (TGF-beta(1)) plays a key role in EMT, the underlying
      cellular mechanisms are not well understood. Here we characterized TGF-beta(1)
      induced EMT in LLC-PK(1) cells and examined the role of the small GTPase Rho and
      its effector, Rho kinase, (ROK) in the ensuing cytoskeletal remodeling and SMA
      expression. TGF-beta(1) treatment caused delocalization and downregulation of
      cell contact proteins (ZO-1, E-cadherin, beta-catenin), cytoskeleton
      reorganization (stress fiber assembly, myosin light chain phosphorylation), and
      robust SMA synthesis. TGF-beta(1) induced a biphasic Rho activation. Stress fiber
      assembly was prevented by the Rho-inhibiting C3 transferase and by dominant
      negative (DN) ROK. The SMA promoter was activated strongly by constitutively
      active Rho but not ROK. Accordingly, TGF-beta(1)-induced SMA promoter activation
      was potently abrogated by two Rho-inhibiting constructs, C3 transferase and
      p190RhoGAP, but not by DN-ROK. Truncation analysis showed that the first
      CC(A/T)richGG (CArG B) serum response factor-binding cis element is essential for
      the Rho responsiveness of the SMA promoter. Thus Rho plays a dual role in TGF
      beta(1)-induced EMT of renal epithelial cells. It is indispensable both for
      cytoskeleton remodeling and for the activation of the SMA promoter. The
      cytoskeletal effects are mediated via the Rho/ROK pathway, whereas the
      transcriptional effects are partially ROK independent.

PMID- 12505863
TI  - Effect of partial outlet obstruction on rabbit urinary bladder smooth muscle
      function.
AB  - Bladder outlet obstruction secondary to benign prostate hyperplasia is associated
      with many cellular changes. This study was designed to determine whether these
      changes involve the contractile apparatus. Bladder smooth muscles from rabbits
      subjected to partial outlet obstruction for 2 wk were mounted for isometric
      force, isotonic shortening velocity, and myosin light chain (MLC) phosphorylation
      levels. Muscle strips from obstructed bladders exhibited spontaneous phasic
      activity; muscle strips from control bladders did not. Muscle strips from
      obstructed bladders exhibited increased sensitivity and higher levels of stress
      in response to the cumulative addition of KCl or carbachol compared with control.
      During noncumulative addition of KCl or carbachol, no differences in sensitivity
      were noted. Muscle strips from obstructed bladders had elevated basal MLC
      phosphorylation levels and stimulation produced small increases in MLC
      phosphorylation compared with control. V(max) during KCl stimulation of muscle
      strips from obstructed bladders was 10-fold lower than control. Our results
      suggest that bladder outlet obstruction produces a muscle cell that develops
      higher levels of force but with greatly reduced cross bridge cycling rates.

PMID- 12505864
TI  - PTH stimulates a Cl(-)-dependent and EIPA-sensitive current in chick proximal
      tubule cells in culture.
AB  - The electrophysiological effects of parathyroid hormone (PTH) were studied in a
      primary cell culture model of the chick (Gallus domesticus) proximal tubule. In
      this model, confluent monolayers are grown on permeable filters and exhibit
      vectorial transport, including glucose-stimulated current. Under short-circuit
      conditions, PTH, at 10(-9) M, induced a positive current [short-circuit current
      (I(sc))] response, with an average 2-min peak response of 14.30 +/- 1.58
      microA/cm(2) over the baseline I(sc,) followed by a slow decay. The PTH response
      was dose dependent, with a half-maximal response at 5 x 10(-9) M and maximal
      response at 5 x 10(-8) M. Forskolin and dibutyryl-cAMP also stimulated I(sc), as
      did the phosphodiesterase inhibitor IBMX. In contrast, the phorbol ester PMA
      inhibited baseline I(sc). The PTH response was nearly abolished by apical
      addition of 100 microM EIPA, an inhibitor of Na(+)/H(+) exchangers, and partially
      blocked by the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid
      (NPPB; 100 microM) and glibenclamide (300 microM). Higher doses of EIPA or NPPB
      alone (500 microM) were almost fully effective, with no or slight additional
      effects of NPPB or EIPA, respectively. The anion exchange inhibitor DIDS (100
      microM) and the Na(+) channel blocker amiloride (10 microM) had no effect.
      Bilateral reduction of Cl(-) in the buffer, from 137 to 2.6 mM, abolished the PTH
      response; increasing Cl(-) concentration restored the I(sc) response, with a half
      maximal effect at 50 mM. These data suggest that, in the chick proximal tubule,
      PTH activates both an Na(+)/H(+) exchanger and a Cl(-) channel that may be
      functionally linked.

PMID- 12505865
TI  - Proinflammatory effects of oxidative stress in chronic kidney disease: role of
      additional angiotensin II blockade.
AB  - Oxidative stress plays an important role in causing progressive chronic kidney
      disease (CKD). We examined the influence of add-on ANG II receptor blockade
      administered as losartan (50 mg/day for 1 mo) on oxidative stress and
      proinflammatory state of the kidney in patients with CKD. All subjects were
      taking an angiotensin-converting enzyme inhibitor plus other antihypertensive
      agents. Oxidative stress to lipids and proteins was measured by an HPLC assay for
      malondialdehyde (MDA) and carbonyl concentration, respectively. Urinary
      inflammation was measured by monocyte chemotactic protein-1 (MCP-1) excretion
      rate. The etiology of CKD was type 2 diabetes mellitus in 12 and
      glomerulonephritis in 4 patients. There was no change in proteinuria or 24-h
      ambulatory blood pressure (BP) with add-on ANG II receptor blockade with losartan
      therapy. Before losartan therapy, urinary protein and albumin oxidation were 99
      and 71% higher, respectively, compared with in plasma (P < 0.05). There was a 35%
      reduction in urinary oxidized albumin with add-on losartan therapy (P = 0.036).
      Urinary and plasma MDA were elevated compared with age-matched controls. Urinary
      MDA was significantly reduced from 4.75 +/- 3.23 to 3.39 +/- 2.17 micromol/g
      creatinine with add-on losartan therapy. However, plasma MDA or oxidized proteins
      did not change in response to additional ANG II blockade. A good correlation was
      seen between the change in urinary oxidized albumin and MCP-1 levels (r = 0.61, P
      = 0.012). These data demonstrate that oxidative damage to urinary protein and
      lipids can be reduced with additional ANG II receptor blockade, independently of
      reductions in proteinuria or BP. Urinary measurements of markers of oxidative
      damage to lipids and proteins appear to be more sensitive than plasma
      measurements in patients with CKD. The significant association of the change in
      urinary MCP-1 with a reduction in oxidative stress supports the role of the redox
      state in the kidney with renal fibrosis and progressive kidney damage.

PMID- 12505866
TI  - Increased cellular activity in rat insular cortex after water and salt ingestion
      induced by fluid depletion.
AB  - Insular cortex (IC) receives inputs from multiple sensory systems, including
      taste, and from receptors that monitor body electrolyte and fluid balance and
      blood pressure. This work analyzed metabolic activity of IC cells after water and
      sodium ingestion induced by sodium depletion. Rats were injected with the
      diuretic furosemide (10 mg/kg body wt), followed 5 min later by injections of the
      angiotensin-converting enzyme inhibitor captopril (5 mg/kg body wt). After 90
      min, some rats received water and 0.3 M NaCl to drink for 2 h while others did
      not. A third group had access to water and saline but was not depleted of fluids.
      All rats were killed for processing of brain tissue for Fos-immunoreactivity (Fos
      ir). Nondepleted animals had weak-to-moderate levels of Fos-ir within subregions
      of IC. Fluid-depleted rats without fluid access had significantly increased Fos
      ir in all areas of IC. Levels of Fos-ir were highest in fluid-depleted rats that
      drank water and sodium. Fos-ir levels were highest in anterior regions of IC and
      lowest in posterior regions of IC. These results implicate visceral, taste,
      and/or postingestional factors in the increased metabolic activity of cells in
      IC.

PMID- 12505867
TI  - Age-related changes in urethrovesical coordination in male rats: relationship
      with bladder instability?
AB  - The micturition profile in conscious animals and the urethrovesical coordination
      in anesthetized conditions were investigated in 6- and 24-mo-old male Sprague
      Dawley rats. The in vitro pharmacological responses to KCl, electrical field
      stimulation (EFS), carbachol, phenylephrine, and isoprenaline were determined in
      the isolated bladder body, the bladder neck, and urethra. A morphometric and
      immunohistological study has been included. During conscious cystomanometry, 63%
      of the aging rats but only 25% of the adult rats showed spontaneous contractions
      during the bladder-filling phase. In conscious aging rats, basal pressure,
      threshold pressure, and micturition pressure were also significantly increased.
      In anesthetized aging rats, a decrease in resting urethral pressure at
      micturition threshold and the occurrence of a significant delay in urethral
      relaxation during micturition were associated with an increased residual volume.
      In all isolated tissues, contractile response to KCl was not modified with aging,
      whereas age-related decreases in maximal responses to carbachol in the bladder
      body and to phenylephrine and carbachol in the urethra were observed. In the
      bladder neck only, we found a significant decrease in the amplitude of neurogenic
      contractions associated with fibrosis but without decrease in nerve density.
      These experiments show significant modifications in the voiding pattern of aging
      rats associated with urethral dysfunction and with regionally specific
      pharmacological and structural changes of the urinary tract. We propose that
      aging in rats is characterized by an impairment of the urethrovesical
      coordination, leading to bladder dysfunctions similar to those induced by bladder
      outlet obstruction.

PMID- 12505868
TI  - Cell-specific and developmental expression of phospholipase C-gamma and
      diacylglycerol in fetal lung.
AB  - Epidermal growth factor (EGF) receptor (EGFR) regulates development of cell-cell
      communication in fetal lung, but the signal transduction mechanisms involved are
      unknown. We hypothesized that, in late-gestation fetal rat lung, phospholipase C
      gamma (PLC-gamma) expression and activation by EGF is cell specific and
      developmentally regulated. PLC-gamma immunolocalized to cuboidal epithelium and
      mesenchymal clusters underlying developing saccules. PLC-gamma protein increased
      from day 17 to day 19 and then decreased. In cultured fetal lung fibroblasts, EGF
      stimulated PLC-gamma phosphorylation 2.6-fold (day 17), 10.8-fold (day 19), and
      4.2-fold (day 21). EGF stimulated (3)H-labeled diacylglycerol production in
      fibroblasts (beginning on day 18 in female and on day 19 in male rats), but not
      in type II cells at any time during gestation. EGFR blockade abrogated the
      observed stimulation of PLC-gamma phosphorylation by EGF. In conclusion, PLC
      gamma expression and activation by EGF in fetal lung are cell specific,
      corresponding to the development of EGFR expression. EGF induces diacylglycerol
      production in a cell- and gestation-specific manner. PLC-gamma activation by EGFR
      in fetal lung fibroblasts may be involved in EGF control of lung development.

PMID- 12505869
TI  - Recombinant human SP-A1 and SP-A2 proteins have different carbohydrate-binding
      characteristics.
AB  - Surfactant protein (SP)-A is a member of the collectin family of proteins and
      plays a role in innate host defense of the lung. SP-A binds to the carbohydrates
      of lung pathogens via its calcium-dependant carbohydrate-binding domain. Native
      human alveolar SP-A consists of two distinct gene products: SP-A1 and SP-A2;
      however, only SP-A2 is expressed in the submucosal glands of the conducting
      airways. The function of the isolated SP-A2 protein is unknown. We hypothesized
      that SP-A1 and SP-A2 might have different carbohydrate-binding properties. In
      this study, we characterized the carbohydrate-binding specificities of native
      human alveolar SP-A and recombinant human SP-A1 and SP-A2 in the presence of
      either 1 or 5 mM Ca(2+). We found that all of the SP-A proteins bind
      carbohydrates but with different affinities. All of the SP-A proteins bind to
      fucose with the greatest affinity. SP-A2 binds with a higher affinity to a wider
      variety of sugars than SP-A1 at either 1 or 5 mM Ca(2+). These findings are
      suggestive that SP-A2 may interact with a greater variety of pathogens than
      native SP-A.

PMID- 12505870
TI  - A potent inhibitor of cytosolic phospholipase A2, arachidonyl trifluoromethyl
      ketone, attenuates LPS-induced lung injury in mice.
AB  - Acute respiratory distress syndrome (ARDS) is an acute lung injury of high
      mortality rate, and sepsis syndrome is one of the most frequent causes of ARDS.
      Metabolites of arachidonic acid, including thromboxanes and leukotrienes, are
      proinflammatory mediators and potentially involved in the development of ARDS. A
      key enzyme for the production of these inflammatory mediators is cytosolic
      phospholipase A(2) (cPLA(2)). Recently, it has been reported that arachidonyl
      trifluoromethyl ketone (ATK) is a potent inhibitor of cPLA(2). In the present
      study, we hypothesized that pharmacological intervention of cPLA(2) could affect
      acute lung injury. To test this hypothesis, we examined the effects of ATK in a
      murine model of acute lung injury induced by septic syndrome. The treatment with
      ATK significantly attenuated lung injury, polymorphonuclear neutrophil
      sequestration, and deterioration of gas exchange caused by lipopolysaccharide and
      zymosan administration. The current observations suggest that pharmacological
      intervention of cPLA(2) could be a novel therapeutic approach to acute lung
      injury caused by sepsis syndrome.

PMID- 12505871
TI  - P38 MAPK: critical molecule in thrombin-induced NF-kappa B-dependent leukocyte
      recruitment.
AB  - Thrombin-stimulated endothelium synthesizes numerous adhesion molecules to
      recruit leukocytes; however, it is unknown which intracellular pathways are
      responsible for this event. A recent report from our laboratory has shown that
      thrombin induces E-selectin expression and that blocking nuclear factor-kappa B
      (NF-kappa B) activity partially blocked both E-selectin expression (60%) and
      leukocyte recruitment. In this study, we systematically assessed the importance
      of p38 MAPK in thrombin-induced NF-kappa B activation and E-selectin-dependent
      leukocyte recruitment. Thrombin caused phosphorylation of p38 MAPK, its substrate
      ATF-2, and JNK MAPK, but not ERK MAPK. The p38 MAPK inhibitors, SKF86002 and SB
      203580 only reduced ATF-2 activity. We treated human umbilical vein endothelial
      cells with SKF86002, 1 h before thrombin stimulation, and noted inhibition of NF
      kappa B mobilization and complete inhibition of leukocyte rolling and adhesion in
      a laminar flow chamber. Significant inhibition of leukocyte recruitment and E
      selectin expression was also observed with SB-203580. SKF86002 did not affect
      other systems, including tumor necrosis factor-alpha-induced E-selectin-dependent
      leukocyte recruitment. Moreover, thrombin-induced rapid mobilization of P
      selectin from Weibel Palade bodies was not p38 MAPK dependent. These data suggest
      that thrombin induces p38 MAPK activation, which leads to NF-kappa B mobilization
      to the nucleus and causes the upregulation of E-selectin and subsequent leukocyte
      recruitment.

PMID- 12505872
TI  - Physiological concentration of atrial natriuretic peptide induces endothelial
      regeneration in vitro.
AB  - Both nitric oxide (NO) and natriuretic peptides produce apoptosis of vascular
      smooth muscle cells. However, there is evidence that NO induces endothelial cell
      proliferation, which suggests that there is a difference in the response of
      endothelial cells to natriuretic peptides. The purpose of this study was to
      investigate the effect of atrial natriuretic peptide (ANP) on human endothelial
      cell survival. ANP within the physiological concentration (10(-11) mol/l) induced
      a 52% increase in the number of human coronary arterial endothelial cells and a
      63% increase in human umbilical vein endothelial cells at a low concentration of
      serum. The increase in cell numbers was blocked by pretreatment with RP8-CPT-cGMP
      (RP8), a cGMP-dependent protein kinase inhibitor, with wortmannin, an Akt/PKB
      inhibitor, and with PD-98059, an ERK1/2 inhibitor. In a Transwell migration test,
      ANP also increased the cell migration, and RP8, wortmannin, and PD-98059 blocked
      this increase. A wound healing assay was performed to examine the effects of ANP
      on regeneration in vitro. ANP increased both cell numbers and migration, but the
      effects were blocked by the above three kinase inhibitors. ANP increased the
      expression of phospho-Akt and of phospho-ERK1/2 within 1.5 h. These results
      suggest that ANP can potentiate endothelial regeneration by cGMP-dependent
      protein kinase stimulation and subsequent Akt and ERK1/2 activations.

PMID- 12505873
TI  - Modulation of collateral artery growth in a porcine hindlimb ligation model using
      MCP-1.
AB  - For an appropriate extrapolation to patients with peripheral arterial obstructive
      disease, we tested the efficacy of monocyte chemoattractant protein 1 (MCP-1)
      treatment in a porcine hindlimb ligation model. In 40 minipigs, a femoral artery
      ligation was performed. Control animals were examined immediately after ligation
      (n = 4) or after 2 wk of intra-arterial infusion of PBS (n = 11). A second group
      of animals was evaluated after intra-arterial infusion of 2.0 microg/h of MCP-1
      for 48 h (followed by 12 days of PBS; n = 13) or 2 wk continuously (n = 12). In
      the terminal experiment after 2 wk, resting flow to the leg and peripheral
      arterial pressures were assessed without vasodilatation. Subsequently, vascular
      conductance was determined by using a pump-driven extracorporal circulation
      during maximal vasodilatation. The results showed that resting blood flow to the
      hindlimb was 53% of the normal after 2 wk of infusion of PBS, compared with 81%
      in both MCP-1 treatment groups (P < 0.05). Collateral conductance was 645 +/- 346
      ml x min(-1) x mmHg(-1) after 2 wk of infusion with PBS, compared with 1,070 +/-
      530 and 1,158 +/- 535 ml x min(-1) x mmHg(-1) after 48 h and 2 wk treatment with
      MCP-1, respectively (P < 0.05). Modulation of the process of arteriogenesis is
      feasible in this large animal model via intra-arterial infusion of the Cys-Cys
      chemokine MCP-1.

PMID- 12505874
TI  - Gene transfer of extracellular SOD to the penis reduces O2-* and improves
      erectile function in aged rats.
AB  - Increased superoxide anion (O(2)(-).) may contribute to vascular dysfunction in
      aging. In aged cavernosal tissue, lucigenin-enhanced chemiluminescence
      demonstrated a threefold increase in superoxide formation, and the oxidative
      fluorescent probe hydroethidine indicated higher superoxide levels throughout the
      aged penis. This increase in superoxide was associated with impaired cavernosal
      nerve-mediated and agonist-induced erectile responses, increased nitrotyrosine
      staining, and lower cGMP levels, but no compensatory change in cavernosal
      extracellular (EC)-superoxide dismutase (EC-SOD) mRNA or protein. In vivo
      adenoviral (Ad) gene transfer of EC-SOD to the penis resulted in higher
      expression of EC-SOD mRNA, protein, SOD activity, cGMP levels, and lower
      nitrotyrosine staining. Transfection with AdCMVEC-SOD resulted in a significant
      increase in erectile response to cavernosal nerve stimulation, ACh, and zaprinast
      to a magnitude similar to young rats. These data provide evidence in support of
      the hypothesis that erectile dysfunction associated with aging is related in part
      to an increase in cavernosal O(2)(-). formation. Gene-transfer of EC-SOD reduces
      superoxide formation and restores age-associated erectile function and may
      represent a novel therapeutic target for the treatment of erectile dysfunction.

PMID- 12505875
TI  - Protein kinase C-epsilon-null mice have decreased hypoxic pulmonary
      vasoconstriction.
AB  - PKC contributes to regulation of pulmonary vascular reactivity in response to
      hypoxia. The role of individual PKC isozymes is less clear. We used a knockout
      (null, -/-) mouse to test the hypothesis that PKC-epsilon is important in acute
      hypoxic pulmonary vasoconstriction (HPV). We asked whether deletion of PKC
      epsilon would decrease acute HPV in adult C57BL6xSV129 mice. In isolated, salt
      solution-perfused lung, reactivity to acute hypoxic challenges (0% and 3% O(2))
      was compared with responses to angiotensin II (ANG II) and KCl. PKC-epsilon -/-
      mice had decreased HPV, whereas responses to ANG II and KCl were preserved.
      Inhibition of nitric oxide synthase (NOS) with nitro-l-arginine augmented HPV in
      PKC-epsilon +/+ but not -/- mice. Inhibition of Ca(2+)-gated K(+) channels
      (K(Ca)) with charybdotoxin and apamin did not enhance HPV in -/- mice relative to
      wild-type (+/+) controls. In contrast, the voltage-gated K(+) channel (K(V))
      antagonist 4-aminopyridine increased the response of -/- mice beyond that of +/+
      mice. This suggested that increased K(V) channel expression could contribute to
      blunted HPV in PKC-epsilon -/- mice. Therefore, expression of the O(2)-sensitive
      K(V) channel subunit Kv3.1b (100-kDa glycosylated form and 70-kDa core protein)
      was compared in whole lung and pulmonary artery smooth muscle cell (PASMC)
      lysates from +/+ and -/- mice. A subtle increase in Kv3.1b was detected in -/-
      vs. +/+ whole lung lysates. A much greater rise in Kv3.1b expression was found in
      -/- vs. +/+ PASMC. Thus deletion of PKC-epsilon blunts murine HPV. The decreased
      response could not be attributed to a general loss in vasoreactivity or
      derangements in NOS or K(Ca) channel activity. Instead, the absence of PKC
      epsilon allows increased expression of K(V) channels (like Kv3.1b) to occur in
      PASMC, which likely contributes to decreased HPV.

PMID- 12505876
TI  - Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin.
AB  - Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of
      this study was to test the hypothesis that a reduction in nitric oxide (NO)
      dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation
      in older subjects. Seven young (23 +/- 2 yr) and seven older (71 +/- 6 yr) men
      were instrumented with two microdialysis fibers in the forearm skin. One site
      served as control (Ringer infusion), and the second site was perfused with 10 mM
      N(G)-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the
      protocol. Water-perfused suits were used to raise core temperature 1.0 degrees C.
      Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each
      microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC
      flux per mean arterial pressure, with values expressed as a percentage of maximal
      vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC
      from 75 +/- 6% maximal CVC (CVC(max)) to 53 +/- 3% CVC(max) in the young subjects
      and from 64 +/- 5% CVC(max) to 29 +/- 2% CVC(max) in the older subjects with a
      1.0 degrees C rise in core temperature. Thus the relative NO-dependent portion of
      cutaneous active vasodilation (AVD) accounted for approximately 23% of
      vasodilation in the young subjects and 60% of the vasodilation in the older
      subjects at this level of hyperthermia (P < 0.001). In summary, NO-mediated
      pathways contributed more to the total vasodilatory response of the older
      subjects at high core temperatures. This suggests that attenuated cutaneous
      vasodilation with age may be due to a reduction in, or decreased vascular
      responsiveness to, the unknown neurotransmitter(s) mediating AVD.

PMID- 12505877
TI  - Gene therapy vector-mediated expression of insulin-like growth factors protects
      cardiomyocytes from apoptosis and enhances neovascularization.
AB  - IGF-I and IGF-II are single-chain polypeptide growth factors that regulate
      pleiotropic cellular responses. We have characterized the effect of recombinant
      IGF proteins, as well as third-generation adenoviral vectors encoding either IGF
      I or IGF-II genes, on cardiomyocyte apoptosis and on angiogenesis. We found that
      endothelial cells cultured in the presence of the extracellular protein laminin
      exhibit a robust response to IGF-I and -II proteins via enhanced cell migration
      and angiogenic outgrowth. Furthermore, IGF vectors greatly enhanced
      neovascularization in an in vivo Matrigel model. Transduction of cardiomyocytes
      with the IGF adenoviral vectors resulted in a dose- and time-dependent increase
      in the expression of IGF-I or IGF-II protein. This correlated with abrogation of
      apoptosis induced by ischemia-reoxygenation, ceramide, or heat shock with optimal
      inhibition of approximately 80%. We conclude that gene transfer of IGF-I and IGF
      II is a plausible strategy for the local delivery of IGFs to treat ischemic heart
      disease and heart failure by stimulating angiogenesis and protecting
      cardiomyocytes from cell death.

PMID- 12505878
TI  - Pressure pulses and flow velocities in central veins of the anesthetized sheep
      fetus.
AB  - The pressure drop and pressure pulses in the isthmus of the ductus venosus (DV)
      in fetal sheep have not been measured directly and related to flow. In eight
      acutely anesthetized fetal sheep, a 3-Fr tip pressure transducer (TP) was
      inserted from the external jugular into the umbilical vein (UV). Ultrasound
      Doppler flow velocities, TP position, and intravenous pressures were recorded in
      the UV, DV, and inferior vena cava (VC) while the TP was withdrawn. Flow was
      steady in the UV, but small pressure fluctuations (<0.4 mmHg) could be detected.
      Time-averaged pressure dropped 1.9 mmHg (mean; 0.5-3.3 mmHg 95% confidence
      interval) across the DV isthmus. Pressure pulses increased from 1.7 mmHg (mean;
      1.2-2.1 mmHg 95% confidence interval) in the DV to 3.9 mmHg (mean; 1.8-6.0 mmHg
      95% confidence interval) in the inferior VC. The pressure wave from the heart
      arrived later [0.053 s (mean; 0.025-0.080 s 95% confidence interval)] in the
      isthmus of the DV than in the diaphragmatic inferior VC, indicating a wave
      velocity of approximately 1.1 m/s. At all locations, pressures and flow
      velocities were inversely related.

PMID- 12505879
TI  - Stimulation of perivascular nitric oxide synthesis by oxygen.
AB  - We hypothesized that elevated partial pressures of O(2) would increase
      perivascular nitric oxide (*NO) synthesis. Rodents with O(2)- and.NO-specific
      microelectrodes implanted adjacent to the abdominal aorta were exposed to O(2) at
      partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0
      and 2.8 ATA O(2) stimulated neuronal (type I) NO synthase (nNOS) and
      significantly increased steady-state.NO concentration, but the mechanism for
      enzyme activation differed at each partial pressure. At both pressures,
      elevations in.NO concentration were inhibited by the nNOS inhibitor 7
      nitroindazole and the calcium channel blocker nimodipine. Enzyme activation at
      2.0 ATA O(2) appeared to be due to an altered cellular redox state. Exposure to
      2.8 ATA O(2), but not 2.0 ATA O(2), increased nNOS activity by enhancing nNOS
      association with calmodulin, and an inhibitory effect of geldanamycin indicated
      that the association was facilitated by heat shock protein 90. Infusion of
      superoxide dismutase inhibited.NO elevation at 2.8 but not 2.0 ATA O(2).
      Hyperoxia increased the concentration of.NO associated with hemoglobin. These
      findings highlight the complexity of oxidative stress responses and may help
      explain some of the dose responses associated with therapeutic applications of
      hyperbaric oxygen.

PMID- 12505880
TI  - Bryostatin-1 attenuates TNF-induced epithelial barrier dysfunction: role of novel
      PKC isozymes.
AB  - Tumor necrosis factor (TNF) increases epithelial permeability in many model
      systems. Protein kinase C (PKC) isozymes regulate epithelial barrier function and
      alter ligand-receptor interactions. We sought to define the impact of PKC on TNF
      induced barrier dysfunction in T84 intestinal epithelia. TNF induced a dose- and
      time-dependent fall in transepithelial electrical resistance (TER) and an
      increase in [(3)H]mannitol flux. The TNF-induced fall in TER was not PKC mediated
      but was prevented by pretreatment with bryostatin-1, a PKC agonist. As
      demonstrated by a pattern of sensitivity to pharmacological inhibitors of PKC,
      this epithelial barrier preservation was mediated by novel PKC isozymes.
      Bryostatin-1 reduced TNF receptor (TNF-R1) surface availability, as demonstrated
      by radiolabeled TNF binding and cell surface biotinylation assays, and increased
      TNF-R1 receptor shedding. The pattern of sensitivity to isozyme-selective PKC
      inhibitors suggested that these effects were mediated by activation of PKC
      epsilon. In addition, after bryostatin-1 treatment, PKC-delta and TNF-R1 became
      associated, as determined by mutual coimmunoprecipitation assay, which has been
      shown to lead to receptor desensitization in neutrophils. TNF-induced barrier
      dysfunction occurs independently of PKC, but selective modulation of novel PKC
      isozymes may regulate TNF-R1 signaling.

PMID- 12505881
TI  - Role of luminal nutrients and endogenous GLP-2 in intestinal adaptation to mid
      small bowel resection.
AB  - To elucidate the role of luminal nutrients and glucagon-like peptide-2 (GLP-2) in
      intestinal adaptation, rats were subjected to 70% midjejunoileal resection or
      ileal transection and were maintained with total parenteral nutrition (TPN) or
      oral feeding. TPN rats showed small bowel mucosal hyperplasia at 8 h through 7
      days after resection, demonstrating that exogenous luminal nutrients are not
      essential for resection-induced adaptation when residual ileum and colon are
      present. Increased enterocyte proliferation was a stronger determinant of
      resection-induced mucosal growth in orally fed animals, whereas decreased
      apoptosis showed a greater effect in TPN animals. Resection induced significant
      transient increases in plasma bioactive GLP-2 during TPN, whereas resection
      induced sustained increases in plasma GLP-2 during oral feeding. Resection
      induced adaptive growth in TPN and orally fed rats was associated with a
      significant positive correlation between increases in plasma bioactive GLP-2 and
      proglucagon mRNA expression in the colon of TPN rats and ileum of orally fed
      rats. These data support a significant role for endogenous GLP-2 in the adaptive
      response to mid-small bowel resection in both TPN and orally fed rats.

PMID- 12505882
TI  - Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma
      expression and decrease of PKA activity.
AB  - To determine the role and mechanisms of action by which dopaminergic innervation
      modulates ductal secretion in bile duct-ligated rats, we determined the
      expression of D1, D2, and D3 dopaminergic receptors in cholangiocytes. We
      evaluated whether D1, D2 (quinelorane), or D3 dopaminergic receptor agonists
      influence basal and secretin-stimulated choleresis and lumen expansion in
      intrahepatic bile duct units (IBDU) and cAMP levels in cholangiocytes in the
      absence or presence of BAPTA-AM, chelerythrine, 1-(5-isoquinolinylsulfonyl)-2
      methyl piperazine (H7), or rottlerin. We evaluated whether 1) quinelorane effects
      on ductal secretion were associated with increased expression of Ca(2+)-dependent
      PKC isoforms and 2) increased expression of PKC causes inhibition of PKA
      activity. Quinelorane inhibited secretin-stimulated choleresis in vivo and IBDU
      lumen space, cAMP levels, and PKA activity in cholangiocytes. The inhibitory
      effects of quinelorane on secretin-stimulated ductal secretion and PKA activity
      were blocked by BAPTA-AM, chelerythrine, and H7. Quinelorane effects on ductal
      secretion were associated with activation of the Ca(2+)-dependent PKC-gamma but
      not other PKC isoforms. The dopaminergic nervous system counterregulates secretin
      stimulated ductal secretion in experimental cholestasis.

PMID- 12505883
TI  - Neuronal locus and cellular signaling for stimulation of ileal giant migrating
      and phasic contractions.
AB  - We investigated the neuronal locus, the role of PKC activation, and utilization
      of extracellular Ca(2+) and intracellular Ca(2+) release in smooth muscle cells
      for the generation of giant migrating contractions (GMCs) and rhythmic phasic
      contractions (RPCs) in intact normal and inflamed canine ileum. Calcitonin gene
      related peptide (CGRP), administered close intra-arterially, stimulated GMCs at
      higher doses and RPCs at smaller doses. These effects were blocked by prior close
      intra-arterial infusions of CGRP(8-37), atropine, hexamethonium, and TTX but not
      by tachykinin, serotonin, and histaminergic receptor subtype antagonists. Both
      types of contractions were blocked by verapamil in normal and inflamed ileums.
      Dantrolene and ruthenium red blocked only the RPCs in normal ileum but blocked
      both GMCs and RPCs in the inflamed ileum. PKC inhibition by chelerythrine blocked
      GMCs only in inflamed ileum but blocked RPCs in both normal and inflamed ileums.
      The inhibition of phospholipase C by neomycin blocked both RPCs and GMCs in
      normal and inflamed ileums. In conclusion, acetylcholine is the common
      neurotransmitter for the stimulation of both GMCs and RPCs, but the signaling
      cascades for their stimulation are partially divergent, and they differ also in
      the normal and inflamed states.

PMID- 12505884
TI  - Neighborhood support and the birth weight of urban infants.
AB  - Differences in maternal characteristics only partially explain the lower birth
      weights of infants of African-American women. It is hypothesized that economic
      and social features of urban neighborhoods may further account for these
      differences. The authors conducted a household survey of 8,782 adults residing in
      343 Chicago, Illinois, neighborhoods to assess mean levels of perceived social
      support and used US Census data to estimate neighborhood economic disadvantage.
      Data on birth weight and maternal risk factors were gathered from 95,711 birth
      certificates (1994-1996). Before statistical adjustment of the data, infants born
      to African-American mothers were found to be, on average, 297 g lighter than
      those born to White mothers. After adjustment for individual-level risk factors,
      this difference was reduced to 154 g. For African-American mothers only, mean
      birth weight decreased significantly as the neighborhood level of economic
      disadvantage increased. For White mothers only, a significant positive
      association was found between perceived levels of neighborhood social support and
      infant birth weight. Adding these neighborhood-level predictors to the model
      reduced the adjusted White versus African-American difference in birth weight to
      124 g. Results support the hypothesis that neighborhood-level factors are
      significantly associated with infant birth weight.

PMID- 12505885
TI  - Invited commentary: Advancing theory and methods for multilevel models of
      residential neighborhoods and health.

PMID- 12505886
TI  - Maternal stress and preterm birth.
AB  - This study examined a comprehensive array of psychosocial factors, including life
      events, social support, depression, pregnancy-related anxiety, perceived
      discrimination, and neighborhood safety in relation to preterm birth (<37 weeks)
      in a prospective cohort study of 1,962 pregnant women in central North Carolina
      between 1996 and 2000, in which 12% delivered preterm. There was an increased
      risk of preterm birth among women with high counts of pregnancy-related anxiety
      (risk ratio (RR) = 2.1, 95% confidence interval (CI): 1.5, 3.0), with life events
      to which the respondent assigned a negative impact weight (RR = 1.8, 95% CI: 1.2,
      2.7), and with a perception of racial discrimination (RR = 1.4, 95% CI: 1.0,
      2.0). Different levels of social support or depression were not associated with
      preterm birth. Preterm birth initiated by labor or ruptured membranes was
      associated with pregnancy-related anxiety among women assigning a high level of
      negative impact weights (RR = 3.0, 95% CI: 1.7, 5.3). The association between
      high levels of pregnancy-related anxiety and preterm birth was reduced when
      restricted to women without medical comorbidities, but the association was not
      eliminated. The prospective collection of multiple psychosocial measures on a
      large population of women indicates that a subset of these factors is associated
      with preterm birth.

PMID- 12505887
TI  - Endogenous hormones and carotid atherosclerosis in elderly men.
AB  - The aging process is characterized by a number of gradual changes in circulating
      hormone concentrations as well as a gradual increase in the degree of
      atherosclerosis. The authors studied whether serum hormone levels are related to
      atherosclerosis of the carotid artery in independently living, elderly men. In
      1996, 403 men (aged 73-94 years) were randomly selected from the general
      population of Zoetermeer, the Netherlands. Carotid artery intima-media thickness
      was determined. Serum concentrations of testosterone; estrone; estradiol;
      dehydroepiandrosterone and dehydroepiandrosterone sulfate; insulin-like growth
      factor I (IGF-I) (total and free) and its binding proteins IGFBP-1, IGFBP-2, and
      IGFBP-3; and leptin were measured. After the authors adjusted for age, serum
      testosterone, estrone, and free IGF-I were inversely related to intima-media
      thickness. The strength of these relations was as powerful in subjects with as in
      those without prevalent cardiovascular disease. Serum estradiol;
      dehydroepiandrosterone sulfate; total IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3; and
      leptin showed no association. These findings suggest that endogenous
      testosterone, estrone, and free IGF-I levels may play a protective role in the
      development of atherosclerosis in aging men.

PMID- 12505888
TI  - Fat and protein intakes and risk of intraparenchymal hemorrhage among middle-aged
      Japanese.
AB  - The authors examined the relation between low intakes of saturated fat and animal
      protein and risk of intraparenchymal hemorrhage in a 14-year prospective study
      (ending in 1997) of 4,775 Japanese aged 40-69 years who undertook a single 24
      hour dietary recall. Compared with the highest quartile of energy-adjusted
      saturated fat intake (median, 17 g/day), multivariate relative risks, after
      adjustment for age, sex, community, total energy intake, and known cardiovascular
      risk factors, were 0.77 (95% confidence interval (CI): 0.42, 1.42) for the second
      quartile (12 g/day), 0.66 (95% CI: 0.34, 1.25) for the third quartile (8 g/day),
      and 0.30 (95% CI: 0.12, 0.71) for the lowest quartile (5 g/day); p for trend =
      0.005. An inverse relation was observed among both hypertensives and
      nonhypertensives; the respective relative risks with a one standard deviation
      increase in saturated fat intake (15.4 g/day) were 0.72 (95% CI: 0.52, 1.00) and
      0.36 (95% CI: 0.14, 0.95). Intake of animal protein tended to correlate inversely
      with risk; the relative risk with a one standard deviation increase in animal
      protein intake (17.6 g/day) was 0.79 (95% CI: 0.61, 1.02); p = 0.07. Results are
      similar to those recently reported for US women and together help to explain the
      high rate of this stroke subtype in Asian countries, where intakes of these
      nutrients are low.

PMID- 12505889
TI  - Risk factors for resistance to antimicrobial agents among nursing home residents.
AB  - The authors prospectively collected data on exposure to antimicrobial agents and
      susceptibility patterns among all clinical isolates of bacteria taken from 9,156
      residents of 50 nursing homes in Canada and the United States in 1998-1999.
      Exposure to antimicrobial agents was measured during the 10 weeks prior to
      detection of targeted resistant bacteria in residents and compared with
      antibiotic exposure during a 10-week interval in individuals with sensitive
      organisms. These main effects were adjusted for infection-control and staffing
      covariates using multiple logistic regression modeling. Increased staffing of
      nursing homes with registered nurses (adjusted odds ratio (OR) = 0.79 (95%
      confidence interval (CI): 0.72, 0.87) per registered nurse per 100 resident-days)
      and use of antibacterial soap (adjusted OR = 0.40, 95% CI: 0.18, 0.90) were
      associated with reduced risk of methicillin-resistant Staphylococcus aureus in
      nursing home residents. An increase in the number of hand-washing sinks per 100
      residents was shown to reduce the risk of trimethoprim-sulfamethoxazole (TMP/SMX)
      resistant Enterobacteriaceae (adjusted OR = 0.94, 95% CI: 0.90, 0.98). Exposure
      to TMP-SMX and exposure to fluoroquinolones were significant risk factors for
      isolation of TMP-SMX-resistant Enterobacteriaciae (adjusted OR = 1.14, 95% CI:
      1.06, 1.22) and fluoroquinolone-resistant Enterobacteriaciae (adjusted OR = 1.08,
      95% CI: 1.04, 1.11), respectively. These findings suggest that increased
      staffing, more hand-washing sinks, and use of antimicrobial soap may reduce
      resistance to antimicrobial agents in long-term care facilities.

PMID- 12505890
TI  - Epidemiology of salmonellosis in California, 1990-1999: morbidity, mortality, and
      hospitalization costs.
AB  - Salmonella is a common cause of bacterial foodborne illness in the United States.
      The epidemiology and costs of nontyphoidal salmonellosis in California from 1990
      through 1999 are described using surveillance, hospitalization, and death data.
      Trends in Salmonella rates and factors associated with prolonged hospitalization
      were evaluated using Poisson and linear regression models, respectively. There
      were 56,660 reported cases, 11,102 hospitalizations, and 74 deaths attributed to
      Samonella. Reported case and hospital discharge rates have decreased since 1996.
      Among reported cases, infants had the highest rate (121 cases per 10(5) person
      years), followed by children 1-4 years of age (40 cases per 10(5) person-years).
      The highest hospitalization rates were among the elderly and young children. Most
      deaths occurred among persons aged 65 or more years (59%). Among
      hospitalizations, gastroenteritis (61%) and septicemia (23%) were the most common
      Salmonella diagnoses. Salmonella pneumonia patients were the oldest (median age,
      55 years) and Salmonella meningitis patients the youngest (median age, 0.3
      years). These two diagnoses were the costliest, approaching 30,000 dollars
      (median) per hospitalization. Having an acquired immunodeficiency syndrome
      diagnosis or multiple Salmonella diagnoses was independently associated with
      prolonged hospitalization. The estimated 10-year hospitalization costs for
      Salmonella were $200 million. Salmonellosis is a costly disease that
      disproportionately affects the young and elderly.

PMID- 12505891
TI  - Trends in enteric disease as a cause of death in the United States, 1989-1996.
AB  - The authors examined rates of and trends in enteric disease as a cause of death
      in the United States. The National Center for Health Statistics Multiple Cause of
      Death databases for 1989-1996 were analyzed for International Classification of
      Diseases, Ninth Revision, codes for gastroenteritis due to infectious agents and
      codes describing illness with other enteric pathogens. The highest rates of death
      related to enteric diseases were seen among people older than 75 years, followed
      by children under 1 year of age. Rates increased markedly over time in the 65- to
      74-year age group for bacterial enteric pathogens and in the 35- to 44-year age
      group for viral enteric pathogens. Enteric diseases were the underlying cause of
      death for an average of 2,740 deaths during each year of this study, and the rate
      of death due to enteric-related disease is increasing.

PMID- 12505892
TI  - Characteristics of telephone survey respondents according to willingness to
      participate.
AB  - When conducting epidemiologic case-control studies, some investigators include
      only controls who can be interviewed within a certain time after contact and/or
      do not recontact potential participants who initially refuse, whereas others
      expend considerable effort to recruit reluctant respondents. This additional
      effort is only worthwhile if it results in a sample that is more representative
      of the target population. In this study, the authors used data collected from in
      person interviews of 5,616 female controls to compare characteristics of willing,
      accessible respondents with those of their less accessible or less willing
      counterparts to determine whether or not the two groups differed with respect to
      lifestyle, socioeconomic status, health history, and demographic characteristics.
      Late responders were younger, were more likely to be non-White, were less likely
      to have attended college, and were more likely to be current smokers than early
      responders. Initial refusers were similar to late responders with respect to
      education and race. Initial refusers were also older, were less likely to be
      currently married, were less likely to have a managerial occupation, had fewer
      lifetime sexual partners, and were more likely to have a history of diabetes than
      early responders. These findings suggest that additional effort expended in
      recruiting reluctant respondents may often result in more accurate estimates of
      population characteristics that are of interest in epidemiologic research.

PMID- 12505893
TI  - Multiple imputation of baseline data in the cardiovascular health study.
AB  - Most epidemiologic studies will encounter missing covariate data. Software
      packages typically used for analyzing data delete any cases with a missing
      covariate to perform a complete case analysis. The deletion of cases complicates
      variable selection when different variables are missing on different cases,
      reduces power, and creates the potential for bias in the resulting estimates.
      Recently, software has become available for producing multiple imputations of
      missing data that account for the between-imputation variability. The
      implementation of the software to impute missing baseline data in the setting of
      the Cardiovascular Health Study, a large, observational study, is described.
      Results of exploratory analyses using the imputed data were largely consistent
      with results using only complete cases, even in a situation where one third of
      the cases were excluded from the complete case analysis. There were few
      differences in the exploratory results across three imputations, and the combined
      results from the multiple imputations were very similar to results from a single
      imputation. An increase in power was evident and variable selection simplified
      when using the imputed data sets.

PMID- 12505896
TI  - Re: "Fish and shellfish consumption in relation to death from myocardial
      infarction among men in Shanghai, China".

PMID- 12505898
TI  - Re: "Measures of maternal tobacco exposure and infant birth weight at term".

PMID- 12505901
TI  - Commentary: the 1968 BOHS Chrysotile Asbestos Standard.

PMID- 12505902
TI  - Cold exposure during helicopter rescue operations in the Western Alps.
AB  - OBJECTIVE: The study evaluates exposure to the cold of personnel involved in
      helicopter rescue operations in an alpine environment. METHODS: Rescue operations
      over a period of 15 months in the Oberwallis region (Switzerland) were analysed
      with special regard to the weather conditions, the locality and its altitude, and
      the duration. The equivalent chill temperature was estimated with two independent
      models. "Mean exposure" as well as the "worst-case situation" (based on maximum
      windspeed) were calculated. The results were evaluated according to the "classic"
      Siple-Passel model, the more recent model of Danielsson, ISO 11079, ISO 9920, the
      German industrial standard DIN 33403.5, and the German government regulations for
      work in cold environments ("G21"). RESULTS: The temperature models showed only
      marginal differences in chill temperature. Assuming "worst-case conditions", the
      Siple-Passel model showed that 87.1% of the operations occurred at chill
      temperatures > -30 degrees C, 12.1% in the range of -30 to -45 degrees C, and
      0.8% at <-45 degrees C. The lowest temperature was -54.6 degrees C. The Danielson
      model resulted in 77.6% without the risk of frostbite, 20.1% with >5% risk, 6%
      with >50% risk and 1.8% with >95% risk. According to DIN 33403.5, 1.5% of the
      operations were performed at chill temperatures higher than cold class 1: 2.3%
      are class 1, 13.3% class 2, 34.7% class 3, 34.6% class 4 and 13.7% class 5. The
      maximum exposure times of DIN 33404.5 are exceeded in at least 0.5% of the
      missions. According to ISO 11079, clothing with 2.0 clo is sufficient in 40.2 and
      23.9% of the operations [summer, required clothing insulation (IREQ) min. and
      IREQ neutr., respectively]. In winter the corresponding results are 0.3 and 0.0%.
      Duration of limited exposure is exceeded in 9.1 (IREQ min.) and 19.8% (IREQ
      neutr.) of the operations in summer and in 10.3 and 19.8% in winter. According to
      ISO 9920, ICL min. as well as ICL neutr. is exceeded in 100% in summer and winter
      operations. CONCLUSIONS: Alpine rescue operations are typical of a place of work
      in a cold--sometimes extremely cold--environment. Because of the limited time of
      exposure during the majority of the operations, the most important danger for
      rescue personnel is frostbite, although hypothermia cannot be excluded in cases
      of prolonged operations. Special advice to avoid the specific risks must be given
      to the crews and an examination by occupational medicine, e.g. according to
      "Working in cold environments, G21" of the German Berufsgenossenschaften, is
      recommended. Recommendations for adequate clothing are given.

PMID- 12505903
TI  - Occupational exposure to metalworking fluid mist and sump fluid contaminants.
AB  - This paper summarizes the analytical and occupational hygiene findings from a
      recent survey of occupational exposure to metalworking fluids (MWFs) in the
      engineering industry. The aim of the survey was to link MWF mist exposure
      measurements with particular engineering processes and controls, and utilize the
      data obtained to develop exposure standards. At the same time the opportunity was
      taken to assess fluid management and control, including bacterial and fines
      contamination in the machine sumps. In general, occupational exposure to mineral
      oil MWF mist was controlled to <3 mg/m(3) (8 h time-weighted average) and to <1
      mg/m(3) for water-mix MWF mist (in terms of the concentrate). These exposure
      values do not necessarily represent best practice, but are believed to be
      achievable and representative of industry as a whole. Gravimetric analysis of the
      total inhalable particulate was found to be a good predictor of mineral oil MWF
      mist but not for water-mix MWF mist. Grinding and drilling operations produced
      higher exposures than turning and milling for water-mix fluids. There were
      insufficient data to compare machining operations for mineral oil MWFs. On the
      whole, fluid management was found to be poor, with most sites failing to meet
      industry good practice or Health & Safety Executive (HSE) standards. Some of the
      operating procedures utilized were deficient or unsatisfactory. Poor standards of
      fluid management were found at all sizes of company. High levels of bacteria,
      endotoxin and fines were found in sumps, and control of other factors, such as
      water-mix fluid concentration, was often poor. Mineral oils had higher levels of
      fines than water-mix fluids (medians of 395 and 18 mg/l, respectively), and
      grinding produced high levels of fines in both types of MWF. Many water-mix sumps
      contained bacterial levels of >1 x 10(6) CFU/ml, and endotoxin levels of >100 000
      EU/ml were not uncommon. The median values were 109 000 CFU/ml and 8039 EU/ml,
      respectively. Mists could potentially contain extensive contamination from
      bacteria and endotoxin. Analysis of the data suggests that sumps operating under
      typical conditions for machining (a temperature of 20 degrees C, a pH of 9 and a
      fluid strength below 10%), also appear to provide optimum conditions for the
      proliferation of bacteria. Low levels of benzo[a]pyrene (median 0.03 micro g/g)
      were found in the mineral oils, and low levels of N-nitrosodiethanolamine (median
      0.4 micro g/ml) were found in the water-mix MWFs. The results of this work will
      contribute to guidance from the HSE, setting out accepted industry good practice,
      including guide values for MWF mist and sump fluid contaminants, with significant
      emphasis on sump fluid management (maintenance and monitoring), as well as
      control issues.

PMID- 12505904
TI  - Evaluation of five extraction protocols for quantification of endotoxin in
      metalworking fluid aerosol.
AB  - OBJECTIVES: Occupational exposures to endotoxin-contaminated, water-based
      metalworking fluids (MWFs) are thought to contribute to cases of respiratory
      illness. Before occupational exposure limits for endotoxin can be proposed,
      accuracy and reproducibility of laboratory measurements must be established. The
      method most commonly used to quantify endotoxin is the Limulus amebocyte lysate
      (LAL) assay and this is the basis for the American Society for Testing and
      Materials (ASTM) method E2144-01. This study was conducted to generate multiple
      samples with similar mass and endotoxin loading in order to compare four
      alternative extraction methods with the ASTM method. METHODS: Using an exposure
      chamber system that provides a uniform distribution of MWF mist, aerosols with
      three concentrations of endotoxins (4.5, 350 and 1141 EU/m(3)) were collected
      simultaneously on multiple filter samples. The filters were examined for
      endotoxin concentration using five different extraction protocols: extraction
      with 1 h shaking at 25 degrees C in 30 ml pyrogen-free water (PFW) (protocol 1)
      or in PFW with 0.05% Tween-20 (protocol 2); or shaking at 68 degrees C in 30 ml
      PFW (protocol 3) or PFW with Tween-20 (protocol 4); or extraction into 20 ml PFW
      with sonication at 25 degrees C and pH adjustment to 7.5 (ASTM protocol).
      RESULTS: The uniformity of the aerosol mass yielded coefficients of variation of
      12.7, 7.7 and 1.4% for the low, medium and high exposure groups, respectively.
      The variance in the endotoxin extraction protocols was highest for the ASTM
      method for the low, medium and high concentration trials. Low, medium and high
      endotoxin groups were statistically different (P < 0.001), but there were no
      statistical differences between extraction protocols within these exposure
      levels. CONCLUSIONS: ASTM method E2144-01 yielded comparable estimations of MWF
      endotoxin aerosol concentrations but with higher variability than the four other
      extraction methods. This study shows that extraction into PFW at 25 degrees C
      with or without Tween-20 was an improvement over the ASTM method in that the
      estimation was more precise and the method is simpler.

PMID- 12505905
TI  - Retrospective exposure assessment and quality control in an international multi
      centre case-control study.
AB  - The paper presents the exposure assessment method and quality control procedure
      used in an international, multi-centre case-control study within a joint Nordic
      and Italian cohort. This study was conducted to evaluate whether occupational
      exposure to carcinogens influenced the predictivity of high frequency of
      chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk.
      Occupational hygienists assessed exposures in each participating country:
      Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen
      or a clastogen was coded in the cohort according to the original CA studies at
      the time of CA testing, but not for the whole work life. An independent
      occupational hygienist coordinated harmonization of the assessment criteria and
      the quality control procedure. The reliability of the exposure assessments was
      calculated as deviation from the majority of the assessors, as Cohen's kappa and
      as overall proportion of the agreements. The reassessment of the exposures
      changed the exposure statuses significantly, when compared with the original
      cohort. Harmonization of the exposure criteria increased the conformity of the
      assessments. The prevalence of exposure was higher among the original assessors
      (the assessor from the same country as the subject) than the average prevalence
      assessed by the other four in the quality control round. The original assessors
      classified more job situations as exposed than the others. Several reasons for
      this are plausible: real country-specific differences, differences in information
      available to the home assessor and the others and misunderstandings or
      difficulties in translation of information. To ensure the consistency of exposure
      assessments in international retrospective case-control studies it is important
      to have a well-planned study protocol. Due to country-specific environments a
      hygienist from each participating country is necessary. A quality control study
      is recommended, to be performed as described, combined with round-table meetings
      to minimize information bias between the assessors.

PMID- 12505906
TI  - Critical evaluation of historical occupational aerosol exposure records:
      applications to nickel and lead.
AB  - Published or unpublished data sets on individual occupational exposure situations
      are frequently combined and used for some wider purpose, either hazard evaluation
      or standards setting. This paper describes a model by which such individual data
      sets for occupational aerosol exposures might be evaluated in terms of their
      usefulness in this regard. For workplace aerosols, the model is centered around
      the particle size-selective framework for aerosol exposure assessment that has
      emerged in recent years as a rational basis for standards setting. In this paper,
      reported occupational exposures to airborne nickel and lead are used as examples.
      In a comprehensive review, 106 published peer-reviewed sources of potentially
      useful exposure data were found for nickel and 111 similar reports for lead. In
      addition, for lead 116 unpublished reports in the form of hazard evaluation
      reports from the US National Institute for Occupational Safety and Health were
      also examined. For both nickel and lead, a wide range of industry sectors was
      represented, and the data sets cover the period from 1930 to the present day. It
      was found that such published data sets are highly inconsistent in terms of the
      criteria by which the data were obtained, notably for the paucity of essential
      details of the methods that were used. In contrast, for the lead exposures, the
      unpublished government reports are more consistent, since they usually followed
      recognized exposure assessment standards. However, the latter may be misleading
      because they may have tended to represent high exposure situations. The
      evaluation model described in this paper provides not only a basis for the
      evaluation of historical exposure data but also guidelines for new exposure
      assessment to be carried out in the future. Meanwhile, although many of the
      historical exposure data sets were found to be generally quite weak in terms of
      their immediate usefulness, attention is drawn to some of their statistical
      properties that might allow their enhancement for the purposes of hazard
      evaluation and retrospective exposure assessment exercises.

PMID- 12505907
TI  - Determination of potential dermal and inhalation operator exposure to malathion
      in greenhouses with the whole body dosimetry method.
AB  - One of the steps during the authorization process of plant protection products
      (PPP) in the European Union is to evaluate the safety of the operator. For this
      purpose, information on the probable levels of operator exposure during the
      proposed uses of the PPP is required. These levels can be estimated by using
      existing mathematical models or from field study data. However, the existing
      models have several shortcomings, including the lack of data for operator
      exposure levels during spray applications by hand lance, especially in
      greenhouses. The present study monitored the potential dermal and inhalation
      operator exposure from hand-held lance applications of malathion on greenhouse
      tomatoes at low and high spraying pressures. The methodology for monitoring
      potential exposure was based on the whole body dosimetry method. Inhalation
      exposure was monitored using personal air pumps and XAD-2 sampling tubes. For the
      monitoring of hand exposure, cotton gloves were used in two trials and rubber
      gloves in another three. The total volumes of spray solution contaminating the
      body of the operator were 25.37 and 35.83 ml/h, corresponding to 0.05 and 0.07%
      of the applied spray solution, respectively, in the case of low pressure knapsack
      applications and from 160.76 to 283.45 ml/h, corresponding to 0.09-0.19% of the
      spray solution applied, in the case of hand lance applications with tractor
      generated high pressure. Counts on gloves depended on the absorbance/repellency
      of the glove material. The potential inhalation exposures were estimated at 0.07
      and 0.09 ml/h in the case of low pressure knapsack applications, based on a
      ventilation rate of 25 l/min. Both potential dermal operator exposure (excluding
      hands) and potential inhalation exposure were increased by a factor of
      approximately 7 when the application pressure was increased from 3 to 18 bar in
      greenhouse trials with a tractor-assisted hand lance, the rest of the application
      conditions being very similar.

PMID- 12505908
TI  - DREAM: a method for semi-quantitative dermal exposure assessment.
AB  - This paper describes a new method (DREAM) for structured, semi-quantitative
      dermal exposure assessment for chemical or biological agents that can be used in
      occupational hygiene or epidemiology. It is anticipated that DREAM could serve as
      an initial assessment of dermal exposure, amongst others, resulting in a ranking
      of tasks and subsequently jobs. DREAM consists of an inventory and evaluation
      part. Two examples of dermal exposure of workers of a car-construction company
      show that DREAM characterizes tasks and gives insight into exposure mechanisms,
      forming a basis for systematic exposure reduction. DREAM supplies estimates for
      exposure levels on the outside clothing layer as well as on skin, and provides
      insight into the distribution of dermal exposure over the body. Together with the
      ranking of tasks and people, this provides information for measurement strategies
      and helps to determine who, where and what to measure. In addition to dermal
      exposure assessment, the systematic description of dermal exposure pathways helps
      to prioritize and determine most adequate measurement strategies and methods.
      DREAM could be a promising approach for structured, semi-quantitative, dermal
      exposure assessment.

PMID- 12505909
TI  - Who qualifies to be an expert?

PMID- 12505911
TI  - Deposited submicrometer particulate.

PMID- 12505912
TI  - Challenges for the anesthesiologist: robotics?

PMID- 12505913
TI  - Spinal cord injury in a child after single-shot epidural anesthesia.

PMID- 12505914
TI  - Anesthesia for robotic repair of the mitral valve: a report of two cases.
AB  - IMPLICATIONS: We describe the anesthetic management of two patients who underwent
      successful mitral valve repair with use of a robot-assisted cardiac surgical
      technique. We describe the robot used, as well as the surgical procedure, and
      highlight aspects of the anesthetic management, in particular the need for one
      lung ventilation and the utility of transesophageal echocardiography.

PMID- 12505915
TI  - Performance evaluation of a new pulse oximeter during mild hypothermic
      cardiopulmonary bypass.
AB  - Newly developed pulse oximeters (POs) are designed to display accurate SpO(2)
      during motion and hypoperfusion. We compared the performance of a new PO, the
      Masimo SET Radical (M), with a conventional PO, the Nihon Kohden AY-900P (N),
      during hypothermic cardiopulmonary bypass. Eighteen patients were studied
      prospectively. PO failure was defined as failure to show no SpO(2) value or show
      incorrect SpO(2) values for longer than 3 min continuously. PO failure occurred
      in 4 and 14 patients with M and N, respectively (P = 0.0022). All 4 patients in
      whom PO failure developed with M were among the 14 patients with N. No SpO(2) was
      provided for 4% +/- 12% of the duration of aorta cross-clamping with M and 36% +/
      39% with N (P = 0.002). Skin temperature and mean arterial blood pressure when
      PO failure started to occur and ended were similar between M and N. PO failure
      easily developed in patients with preoperative diuretic therapy or with
      intraoperative hyperlactatemia in N, but not in M. M was able to display accurate
      SpO(2) values significantly more frequently and longer than N during mild
      hypothermic cardiopulmonary bypass with nonpulsatile flow, suggesting that M is
      more useful for monitoring SpO(2) during hypoperfusion. IMPLICATIONS: We compared
      the performance of a new pulse oximeter with that of a conventional pulse
      oximeter during hypothermic cardiopulmonary bypass with nonpulsatile flow. The
      newly developed device displayed accurate SpO(2) significantly more frequently
      and longer than a conventional oximeter. Newly developed pulse oximeters seem to
      be more useful for monitoring SpO(2) during hypoperfusion.

PMID- 12505916
TI  - Agreements between the prothrombin times of blood treated In Vitro with
      heparinase during cardiopulmonary bypass (CPB) and blood sampled after CPB and
      systemic protamine.
AB  - The prothrombin time (PT) is useful for identifying coagulation factor deficits
      after cardiopulmonary bypass (CPB). However, long processing times and the need
      for fresh frozen plasma (FFP) to be thawed cause delays in factor replacement. We
      hypothesized that, by treating with heparinase, blood sampled toward the end of
      CPB can provide PT results that help to determine the requirement for FFP after
      CPB. Laboratory delays can be eliminated with point-of-care monitors. We studied
      158 adults undergoing nonemergent cardiac surgery. Blood taken before separation
      from CPB was mixed with heparinase, and PT was measured in the laboratory with a
      HemoTec timer. Agreements between these results and laboratory measurements of
      blood taken after systemic protamine were compared by using Bland and Altman
      plots with the threshold of +/-1.0 s. We found that the laboratory PT
      measurements during CPB versus after CPB were compara-ble, but the limits of
      agreement exceeded these thresholds. Similarly, there was unsatisfactory
      agreement between the HemoTec and laboratory PT results measured before, during,
      and after CPB. For each PT measured during CPB, the corresponding confidence
      interval for the postprotamine PT was calculated. During CPB, a laboratory PT of
      < or =16 s or > or =18 s suggests a > or =83% or > or =93% probability of not
      requiring or potentially requiring, respectively, FFP after CPB. We conclude that
      the majority of PT measurements obtained from blood taken before weaning from CPB
      and treated in vitro with heparinase was associated with a high probability of
      whether or not FFP would be needed after CPB. IMPLICATIONS: Coagulation
      dysfunction after cardiopulmonary bypass may contribute to bleeding. Obtaining
      coagulation tests and fresh frozen plasma requires time and delays treatment in
      patients who need fresh frozen plasma. We have devised a technique to provide
      early estimation of postbypass coagulation status.

PMID- 12505917
TI  - Echocardiographic monitoring during induction of general anesthesia with a
      miniaturized esophageal probe.
AB  - Standard transesophageal echocardiography (TEE) does not allow cardiac monitoring
      during the induction of anesthesia because standard probes would limit the
      oropharyngeal space and impair mask ventilation and tracheal intubation. We
      hypothesized that a prototype, miniaturized TEE probe could be safely introduced
      transnasally in awake patients and that mask ventilation and orotracheal
      intubation could be performed while continuously monitoring left ventricular (LV)
      function during the induction of anesthesia. Forty-five patients were studied
      prospectively. The transnasal TEE probe was introduced through one of the nares
      and advanced until a transverse plane image of the LV at the level of the
      papillary muscles was seen. Anesthesia was induced, and the patients were
      ventilated with a mask that had previously been threaded over the TEE probe via a
      central perforation. Probe insertion was successful in 12 patients under local
      anesthesia alone and in an additional 31 patients with a combination of local
      anesthesia and mild sedation. In two cases, probe placement was unsuccessful.
      Overall, hemodynamic variables did not change significantly during insertion. No
      case of significant mucosal bleeding was seen. In one patient, regurgitation of
      gastric contents occurred without affecting the perioperative outcome. The two
      dimensional echocardiogram image quality of the LV during the induction of
      anesthesia was good or acceptable in 95% of patients. We conclude that transnasal
      TEE can effectively be used for cardiac monitoring during the induction of
      general anesthesia. IMPLICATIONS: This study demonstrates that it is feasible and
      generally safe to introduce a miniaturized transesophageal echocardiography probe
      transnasally in awake cardiac risk patients to monitor cardiac performance during
      the induction of general anesthesia.

PMID- 12505918
TI  - Hemodilution does not alter arterial baroreflex control of heart rate in
      anesthetized dogs.
AB  - The cardiovascular effects of acute normovolemic hemodilution (ANH) are
      characterized by increased cardiac output and decreased systemic vascular
      resistance. However, whether arterial baroreflex function is altered by ANH
      remains undetermined. We assigned 23 anesthetized, mechanically ventilated dogs
      to mild ANH (hemoglobin, 7-8 g/dL; n = 11) or profound ANH (hemoglobin, 4-5 g/dL;
      n = 12) achieved by phlebotomy and simultaneous exchange with lactated Ringer's
      solution at 1:3 ratio to maintain constant central venous pressure and pulmonary
      artery occluded pressure. Baroreflex sensitivity was assessed by measurements of
      RR intervals of the electrocardiogram and mean arterial blood pressure (MAP)
      through a femoral artery catheter. Baroreflex responses were triggered by bolus
      IV injections of phenylephrine (25-75 micro g) and nitroprusside (50-100 micro
      g). The linear portion of the baroreflex curves relating RR intervals and MAP
      were used to determine baroreflex sensitivities. Compared with the predilution
      period, both ANH groups had significant increases in cardiac output and decreases
      in systemic vascular resistance (P < 0.01), whereas MAP and heart rate (HR)
      remained unchanged. However, no significant difference was detected between pre
      ANH and post-ANH baroreflex sensitivities in either group. Our results indicate
      that arterial baroreflex control of HR is preserved during ANH to a hemoglobin
      concentration of 4-5 g/dL in anesthetized dogs. IMPLICATIONS: Acute normovolemic
      hemodilution may be preoperatively used to minimize the requirement of allogeneic
      blood products during major surgery. We found that baroreflex function is
      preserved during mild (hemoglobin concentration, 7-8 g/dL) and profound
      hemodilution (hemoglobin concentration, 4-5 g/dL) in pentobarbital-anesthetized
      dogs.

PMID- 12505919
TI  - Target-controlled infusion for remifentanil in vascular patients improves
      hemodynamics and decreases remifentanil requirement.
AB  - Remifentanil is a potent ultra-short-acting opioid, which permits rapid
      emergence. However, remifentanil is expensive and may have detrimental effects on
      hemodynamics in case of overdose. Target-controlled infusion (TCI) permits
      adapting infusion to pharmacokinetic models. In this prospective randomized
      study, we compared intra- and postoperative hemodynamics, remifentanil
      requirement during anesthesia, and postoperative morphine requirement in patients
      scheduled for carotid surgery, and receiving either continuous IV weight-adjusted
      infusion of remifentanil (RIVA) or TCI for remifentanil (TCIR). Forty-six
      patients were enrolled in this study: all were anesthetized by using TCI for
      propofol. Twenty-three received RIVA (0.5 micro g. kg(-1) x min(-1)) for the
      induction of anesthesia and endotracheal intubation, with the infusion rate
      decreased to 0.25 micro g x kg(-1) x min(-1) after intubation, then adapted by
      step of 0.05 micro g x kg(-1) x min(-1) according to hemodynamics. Twenty-three
      patients received TCIR (Minto model, Rugloop), with an effect-site concentration
      at 4 ng/mL during induction, then adapted by step of 1 ng/mL according to
      hemodynamics. All patients received atracurium and a 50% mixture of N(2)O/O(2).
      Hemodynamic variables were recorded each minute. The number and duration of
      hemodynamic events were collected, and total doses of anesthetics (remifentanil
      and propofol) and vasoactive drugs were noted in both groups of patients. Data
      were analyzed by using unpaired t-tests. RIVA was significantly associated with
      more frequent episodes of intraoperative hypotension (16 versus 6, P < 0.001) and
      more frequent episodes of postoperative hypertension and/or tachycardia requiring
      more frequent administration of beta-adrenergic blockers (16 vs 10, P < 0.04) in
      comparison with TCIR. The need for morphine titration was not significantly
      different between groups. TCIR led to a significantly smaller requirement of
      remifentanil (700 +/- 290 versus 1390 +/- 555 micro g, P < 0.001) without
      difference in propofol requirement. This prospective randomized study
      demonstrated that, during carotid endarterectomy, in comparison with patients
      receiving remifentanil using continuous RIVA, TCI results in less hypotensive
      episodes during the induction of anesthesia, in fewer episodes of tachycardia
      and/or hypertension and a smaller beta-adrenergic blocker requirement during
      recovery, and a decrease in remifentanil requirement. Recommendations to prefer
      TCI for remifentanil administration during carotid endarterectomy may be
      justified. IMPLICATIONS: Remifentanil for intraoperative analgesia in carotid
      artery surgery is associated with a better stability in perioperative
      hemodynamics when administered in target-controlled infusion compared with
      continuous weight-adjusted infusion. This may be related to a smaller requirement
      of this drug when using target-controlled infusion, as well as a smooth mode of
      administration.

PMID- 12505920
TI  - A comparison of lactated ringer's solution to hydroxyethyl starch 6% in a model
      of severe hemorrhagic shock and continuous bleeding in dogs.
AB  - In this randomized, controlled study in dogs, we examined the short-term effects
      of blood pressure targeted fluid resuscitation with colloids or crystalloids
      solutions on systemic oxygen delivery, and lactate blood concentration. Fluid
      resuscitation using hydroxyethyl starch (HES) 6% to a mean arterial blood
      pressure (MAP) of 60 mm Hg was compared with lactated Ringer's solution (LR) to a
      MAP of 60 or 80 mm Hg (LR60 and LR80, respectively). The model was one of
      withdrawal of blood to a MAP of 40 mm Hg through an arterial catheter that was
      then connected to a system allowing bleeding to occur throughout the study
      whenever MAP exceeded 40 mm Hg. Target MAP was maintained for 60 min with a
      continuous infusion of the designated fluid replacement. All 15 dogs (5 in each
      group) survived until the last measurement. Blood loss in the LR80 group (2980 +/
      503 mL) (all values mean +/- SD) was larger than in the LR60 and HES60 groups
      (1800 +/- 389 mL, and 1820 +/- 219 mL, respectively) (P < 0.001). Whereas 840 +/-
      219 mL of HES60 was needed to maintain target MAP, 1880 +/- 425 mL of LR was
      needed in the LR60 group, and 4590 +/- 930 mL in the LR80 group (P < 0.001).
      Lactate blood concentrations were smaller and delivered O(2) higher in the HES60
      group (35 +/- 17 mg/dL and 239 +/- 61 mL/min, respectively) in comparison to the
      LR60 group (89 +/- 18 mg/dL and 140 +/- 48 mL/min, respectively) and the LR80
      group (75 +/- 23 mg/dL and 153 +/- 17 mL/min, respectively) (P = 0.02 and P =
      0.026). In conclusion, fluid resuscitation during uncontrolled bleeding, to a
      target MAP of 60 mm Hg, using HES60 resulted in larger oxygen delivery and
      smaller systemic lactate A resuscitation to a target MAP of 60 or 80 mm Hg using
      LR. IMPLICATIONS: Fluid resuscitation to a target mean arterial blood pressure of
      60 mm Hg during uncontrolled bleeding resulted in larger oxygen delivery and
      smaller systemic lactate concentrations when hydroxyethyl starch 6% was used, in
      comparison to lactated Ringer's solution resuscitation to a target mean arterial
      blood pressure of 60 or 80 mm Hg.

PMID- 12505921
TI  - Validity of arterial and mixed venous oxygen saturation measurements in a canine
      hemorrhage model after resuscitation with varying concentrations of hemoglobin
      based oxygen carrier.
AB  - In this study, we evaluated the validity of saturation measurements in mixed
      venous and arterial blood during posthemorrhagic anemia and resuscitation with
      varying levels of hemoglobin-based oxygen carrier (Hemoglobin glutamer-200
      [bovine]; Oxyglobin [Hb-200]). Nineteen anesthetized, splenectomized, mixed-breed
      dogs were anesthetized (two were excluded from the data because they did not
      survive the exsanguination, supporting the validity of the model). Their
      pulmonary arteries were cannulated with the Abbott QVUE Oximetrix 3 catheter. An
      18-gauge catheter was placed in the femoral artery, and a reusable Nellcor probe
      was applied to the tongue. Mixed venous and arterial samples were drawn at
      baseline, after 40% hemorrhage (to keep arterial pressure at 50 mm Hg), and
      postresuscitation with 30 mL/kg of 6% hetastarch in lactated Ringer's solution (n
      = 4), 10 mL/kg of Hb-200, 20 mL/kg of hetastarch (n = 6), 20 mL/kg of Hb-200, and
      10 mL/kg of hetastarch (n = 7). Samples were compared with oxygen content from
      the LEXO2CON-K oxygen analyzer, and oxygen content was calculated for all values
      from the monitors. Results were compared by using analysis of variance. There was
      good correlation (0.97 > or = r > or = 0.92) for the measured versus calculated
      hemoglobin oxygen saturation values at baseline. After resuscitation, the
      correlation between calculated and measured values of oxygen content was
      significantly smaller for all tested instruments. The values of oxygen content
      calculated from the oxygen saturation monitor and from the oximetric pulmonary
      artery can deviate by as much as 20% from directly measured values. We conclude
      that the administration of this oxygen therapeutic may interfere with the values
      of some monitors. IMPLICATIONS: This study evaluated oxygen saturation monitors
      in a canine model of acute blood loss and resuscitation with a blood substitute
      and found that these may interfere with the monitors' results in a dose-dependent
      way.

PMID- 12505922
TI  - The predictive value of modified computerized thromboelastography and platelet
      function analysis for postoperative blood loss in routine cardiac surgery.
AB  - Hemorrhage after cardiopulmonary bypass (CPB) remains a clinical problem. Point
      of-care tests to identify hemostatic disturbances at the bedside are desirable.
      In the present study, we evaluated the predictive value of two point-of-care
      tests on postoperative bleeding after routine cardiac surgery. Prospectively, 255
      consecutive patients were studied to compare the ability of modified
      thromboelastography (ROTEG) as well as a platelet function analyzer (PFA-100) to
      predict postoperative blood loss. Measurements were performed at three time
      points: preoperatively, during CPB, and after protamine administration with three
      modified thromboelastography and PFA tests. The best predictors of increased
      bleeding tendency were the tests performed after CPB. The angle alpha is the best
      predictor (area under the receiver operating characteristic curve 0.69) and, in
      combination with the adenosine diphosphate-PFA test, the predictive accuracy is
      enhanced (area under the receiver operating characteristic curve 0.73). The
      negative predictive value for the angle alpha is 82%, although the positive
      predictive value is small (41%). Thromboelastography is a better predictor than
      PFA. In routine cardiac surgery, impaired hemostasis as identified by point-of
      care tests does not inevitably lead to hemorrhage postoperatively. However,
      patients with normal test results are unlikely to bleed for hemostatic reasons.
      Bleeding in these patients is probably caused surgically. The high negative
      predictive value supports early identification and targeted treatment of surgical
      bleeding by distinguishing it from a significant coagulopathy. IMPLICATIONS:
      Thrombelastography and platelet function analysis in routine cardiac surgery
      demonstrate high negative predictive values for postoperative bleeding, which
      supports early identification and targeted treatment of surgical bleeding by
      distinguishing it from a significant coagulopathy. The positive predictive values
      are small. The best predictors are thrombelastography values obtained after
      cardiopulmonary bypass.

PMID- 12505923
TI  - Citrated blood does not reliably reflect fresh whole blood coagulability in
      trials of in vitro hemodilution.
AB  - IMPLICATIONS: Citration and storage of whole blood markedly alter the
      Thrombelastograph effects of hemodilution on coagulation. The results of
      hemodilution studies in which citrated blood has been used to study coagulation
      may not be reliable.

PMID- 12505924
TI  - Severe myxedema after cardiopulmonary bypass.
AB  - IMPLICATIONS: We report a case illustrating the serious perioperative
      consequences that can potentially result from failure to provide adequate thyroid
      hormone therapy for severe hypothyroidism before cardiac surgery.

PMID- 12505925
TI  - Spinal cord injury in a child caused by an accidental dural puncture with a
      single-shot thoracic epidural needle.
AB  - IMPLICATIONS: A child experienced a spinal cord injury by an accidental dural
      puncture during thoracic epidural anesthesia. A magnetic resonance image was used
      for diagnosis and treatment.

PMID- 12505926
TI  - Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after
      tonsillectomy: a quantitative systematic review.
AB  - The use of nonsteroidal antiinflammatory drugs (NSAIDs) for analgesia after
      tonsillectomy is controversial because NSAIDS, through platelet inhibition, may
      increase the risk of perioperative bleeding. We systematically searched for
      randomized, controlled trials that reported on the incidence of perioperative
      bleeding attributable to the use of NSAIDs in patients undergoing tonsillectomy.
      As secondary outcome measures, we analyzed the quality of pain relief and the
      incidence of postoperative nausea and vomiting. Twenty-five studies with data
      from 970 patients receiving a NSAID and 883 receiving a non-NSAID treatment or a
      placebo were analyzed. Data were combined using a fixed-effect model. Of four
      bleeding end points (intraoperative blood loss, postoperative bleeding, hospital
      admission, and reoperation because of bleeding), only reoperation happened
      significantly more often with NSAIDs: Peto-odds ratio, 2.33 (95% confidence
      interval [CI], 1.12-4.83) and number-needed-to-treat, 60 (95% CI, 34-277).
      Compared with opioids, NSAIDs were equianalgesic, and the risk of emesis was
      significantly decreased (relative risk, 0.73; 95% CI, 0.63-0.85; numbers-needed
      to-treat, 9; 95% CI, 5-19). IMPLICATIONS: The evidence for nonsteroidal
      antiinflammatory drugs to increase the risk of bleeding after tonsillectomy is
      equivocal, and the risk-benefit ratio is not straightforward. There is some
      evidence for an increased likelihood of reoperation because of bleeding. The
      agenda must be one of further research rather than of clinical recommendations.

PMID- 12505927
TI  - Oral tramadol for the treatment of pain of 7-30 days' duration in children.
AB  - IMPLICATIONS: This open-label, multicenter trial was designed to determine the
      safety profile and analgesic efficacy of tramadol for the treatment of painful
      conditions lasting 7-30 days in 7-16-yr-old children. We found that tramadol 1-2
      mg/kg per os every 4-6 h (maximal dose = 8 mg x kg(-1). d(-1), not to exceed 400
      mg/d) is a safe and effective analgesic in this patient population.

PMID- 12505928
TI  - A combined ear sensor for pulse oximetry and carbon dioxide tension monitoring:
      accuracy in critically ill children.
AB  - IMPLICATIONS: A new combined ear sensor was tested for accuracy in 20 critically
      ill children. It provides noninvasive and continuous monitoring of arterial
      oxygen saturation, arterial carbon dioxide tension, and pulse rate. The sensor
      proved to be clinically accurate in the tested range.

PMID- 12505929
TI  - Compression of the pulmonary artery during transesophageal echocardiography in a
      pediatric cardiac patient.
AB  - IMPLICATIONS: Hemodynamic compromise caused by the insertion of the probe for
      transesophageal echocardiography in a patient with severe stenosis of the main
      pulmonary artery is reported for the first time. The first symptom of the
      impending problem was a rapid decrease of end-tidal CO(2).

PMID- 12505930
TI  - Hemodynamic response to caudal epidural clonidine in a pediatric cardiac patient.
AB  - IMPLICATIONS: Postoperative management of sedation and analgesia in pediatric
      cardiac patients presents many challenges. This case report describes a child who
      experienced dramatic clinical improvement with the postoperative use of caudal
      morphine and clonidine after conventional therapy had failed.

PMID- 12505931
TI  - Supplemental oxygen does not reduce the incidence of postoperative nausea and
      vomiting after ambulatory gynecologic laparoscopy.
AB  - Supplemental 80% oxygen administration halves the incidence of postoperative
      nausea and vomiting (PONV) in inpatients. Whether it prevents PONV after
      ambulatory surgery is unknown. We tested the efficacy of supplemental 80% oxygen
      in decreasing the incidence of PONV after ambulatory gynecologic laparoscopy. One
      hundred patients were given a standardized sevoflurane anesthetic. They were
      randomly assigned to two groups: routine oxygen administration with 30% oxygen,
      balance nitrogen (Group A); and supplemental oxygen with 80% oxygen, balance
      nitrogen (Group B). Oxygen was administered during surgery and up to 1 h after
      surgery. The incidence of nausea and vomiting and the need for rescue antiemetics
      did not differ between the groups in the postanesthesia care unit, in the Phase
      II unit, or during the 24-h follow-up. The overall incidence of nausea and
      vomiting during the first postoperative 24 h was 62% in Group A and 55% in Group
      B (P = 0.486). There were no differences in the recovery profiles and patient
      satisfaction between the groups. In this study, supplemental oxygen did not
      prevent PONV in patients undergoing ambulatory gynecologic laparoscopy.
      IMPLICATIONS: Supplemental 80% oxygen administration during surgery and until 1 h
      after surgery compared with 30% oxygen administration did not prevent
      postoperative nausea and vomiting after ambulatory gynecologic laparoscopy.

PMID- 12505932
TI  - Glycine receptors mediate part of the immobility produced by inhaled anesthetics.
AB  - Many inhaled anesthetics potentiate the effect of glycine on inhibitory
      strychnine-sensitive glycine receptors in vitro, supporting the view that this
      receptor could mediate the immobility produced by inhaled anesthetics during
      noxious stimulation (i.e., would underlie minimum alveolar anesthetic
      concentration [MAC]). There are quantitative differences between anesthetics in
      their capacity to potentiate glycine's effect in receptor expression systems:
      halothane (most potentiation), isoflurane (intermediate), and cyclopropane
      (minimal). If glycine receptors mediate MAC, then their blockade in the spinal
      cord should increase the MAC of halothane more than that of isoflurane and
      isoflurane MAC more than cyclopropane MAC; the increases in MAC should be
      proportional to the receptor potentiation produced in vitro. Rats with
      chronically implanted intrathecal catheters were anesthetized with halothane,
      isoflurane, or cyclopropane. During intrathecal infusion of artificial
      cerebrospinal fluid, MAC was determined. Then MAC was re-determined during an
      infusion of 3, 12, 24, or 48 (isoflurane only) micro g/min of strychnine
      (strychnine blocks glycine receptors) in artificial cerebrospinal fluid.
      Strychnine infusion increased MAC in proportion to the enhancement of glycine
      receptors found in vitro. The maximum effect was with an infusion of 12 micro
      g/min. For the combined results at 12 and 24 micro g/min of strychnine, the
      increase in MAC correlated with the extent of in vitro potentiation (r(2) =
      0.82). These results support the hypothesis that glycine receptors mediate part
      of the immobilization produced by inhaled anesthetics. IMPLICATIONS: In vitro,
      halothane potentiates glycine's effect on strychnine-sensitive glycine receptors
      more than isoflurane and isoflurane more than cyclopropane. The present in vivo
      work indicates that antagonism of the glycine receptor with strychnine increases
      minimum alveolar anesthetic concentration for halothane more than isoflurane and
      isoflurane more than cyclopropane. Such results support the notion that glycine
      receptors may mediate part of the immobility produced by inhaled anesthetics.

PMID- 12505933
TI  - Spinal N-methyl-d-aspartate receptors may contribute to the immobilizing action
      of isoflurane.
AB  - We examined whether N-methyl-D-aspartate (NMDA) receptors influence the
      immobilizing effect of isoflurane by a spinal or supraspinal action. We
      antagonized NMDA receptors by intrathecal (IT), intracerebroventricular (ICV),
      and IV administration of MK 801 (a noncompetitive NMDA antagonist) and measured
      the decrease in isoflurane minimum alveolar anesthetic concentration (MAC). We
      also measured MK 801 tissue concentrations in homogenates of upper and lower
      spinal cord, a slice of cerebral cortex, and the whole brain. IT infusion of MK
      801 decreased isoflurane MAC more potently than ICV or IV infusions. The change
      in MAC correlated with the MK 801 concentration in the lower part of the spinal
      cord (P < 0.01) but not with concentrations in supraspinal tissue. The maximal
      effect of IT MK 801 reached a plateau without achieving anesthesia. IV doses 270
      fold larger than the largest IT dose also did not produce anesthesia in the
      absence of isoflurane. These results suggest that the capacity of MK 801 to
      decrease the MAC of isoflurane results from an effect on the spinal cord but that
      spinal NMDA receptors provide only partial mediation of the immobility produced
      by isoflurane. Because neither IT nor IV MK 801 provide complete anesthesia,
      these findings also call into question the notion that NMDA blockade alone
      suffices to produce anesthesia as defined by immobility in the face of noxious
      stimulation. IMPLICATIONS: Spinal cord NMDA receptors may mediate a portion of
      the immobilizing effect of isoflurane. Blockade of NMDA receptors in the cord by
      MK 801 has a MAC-sparing effect, but MK 801 does not, by itself, produce complete
      anesthesia.

PMID- 12505934
TI  - Volatile anesthetics reduce agonist affinity at nicotinic acetylcholine receptors
      in the brain.
AB  - In previous studies we and others have demonstrated that the activation of
      nicotinic acetylcholine receptors (nAChRs) is inhibited by subanesthetic
      concentrations of volatile anesthetics. The mechanism by which activation is
      inhibited is unknown. Studies of the evolutionarily related nAChRs from the
      electric fish Torpedo have suggested that volatile anesthetics alter the affinity
      of the agonist for the receptor. We studied the effect of two volatile
      anesthetics, isoflurane and sevoflurane, on equilibrium binding of the high
      affinity nicotinic agonist epibatidine to nicotinic receptors from mouse brain.
      We studied binding to male and female brain separately, because sex differences
      in nicotine responses have been reported. Male and female brains have equal
      epibatidine binding without anesthetic. Isoflurane and sevoflurane reduce the
      binding of [(3)H]epibatidine to male and female nicotinic receptors, but only at
      concentrations at and above those required for anesthesia. The 50% inhibitory
      concentration for isoflurane inhibition of [(3)H]epibatidine binding to male
      brain was 0.58 +/- 0.07 mM and to female brain was 1.62 +/- 0.30 mM. The 50%
      inhibitory concentration for sevoflurane inhibition of [(3)H]epibatidine binding
      to male brain was 0.77 +/- 0.05 mM and to female brain was 0.77 +/- 0.04 mM.
      There was no statistically significant difference in the effect of either drug
      between sexes (P > 0.05). Although there is a slight decrease in agonist affinity
      at anesthetic concentrations, the marked reductions in nAChR function at
      subanesthetic concentrations cannot be attributed to changes in agonist affinity.
      IMPLICATIONS: Volatile anesthetics reduce the activation of nicotinic
      acetylcholine receptors by an unknown mechanism. We have demonstrated that
      although isoflurane and sevoflurane inhibit agonist affinity, the concentrations
      required are too large to be responsible for the dynamic changes observed.

PMID- 12505935
TI  - Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: the
      effects on agonist enhancement, direct activation, and inhibition.
AB  - At clinically relevant concentrations, ethers, alcohols, and halogenated alkanes
      enhance agonist action on the gamma-aminobutyric acid(A) (GABA(A)) receptor,
      whereas nonhalogenated alkanes do not. Many anesthetics also directly activate
      and/or inhibit GABA(A) receptors, actions that may produce important behavioral
      effects; although, the effects of nonhalogenated alkane anesthetics on GABA(A)
      receptor direct activation and inhibition have not been studied. In this study,
      we assessed the abilities of two representative nonhalogenated alkanes,
      cyclopropane and butane, to enhance agonist action, directly activate, and
      inhibit currents mediated by expressed alpha(1)beta(2)gamma(2L) GABA(A) receptors
      using electrophysiological techniques. Our studies reveal that cyclopro- pane and
      butane enhance agonist action on the GABA(A) receptor at concentrations that
      exceed those required to produce anesthesia. Neither nonhalogenated alkane
      directly activated nor inhibited GABA(A) receptors, even at concentrations that
      approach their aqueous saturated solubilities. These results strongly suggest
      that the behavioral actions of nonhalogenated alkane anesthetics do not result
      from their abilities to enhance agonist actions, directly activate, or inhibit
      alpha(1)beta(2)gamma(2L) GABA(A) receptors and are consistent with the hypothesis
      that electrostatic interactions between anesthetics and their protein binding
      sites modulate GABA(A) receptor potency. IMPLICATIONS: When normalized to either
      their in vivo anesthetic potencies or hydrophobicities, cyclopropane and butane
      are 1-1.5 orders of magnitude less potent enhancers of agonist action on
      alpha(1beta2gamma2L) GABA(A) receptors than isoflurane. Additionally,
      cyclopropane and butane fail to directly activate or inhibit receptors, even at
      near aqueous saturating concentrations. Thus, it is unlikely that either
      enhancement or inhibition of the most common GABA(A) receptor subtype in the
      brain accounts for the behavioral activities of cyclopropane and butane.

PMID- 12505936
TI  - Minimum alveolar anesthetic concentration of isoflurane with different xenon
      concentrations in Swine.
AB  - For patients requiring a fraction of inspired oxygen more than 0.3, the use of
      xenon (Xe) as the sole anesthetic is limited because of its large minimum
      alveolar anesthetic concentration (MAC) of 71%. This warrants investigating the
      combination of Xe with other inhaled anesthetics. We therefore investigated the
      influence of Xe on the MAC of isoflurane. The study was performed in 10 swine
      (weight, 28-35 kg) ventilated with Xe 0%, 15%, 30%, 40%, 50%, and 65% in oxygen.
      For each Xe concentration, various concentrations of isoflurane were administered
      in a step-wise design. For each combination, a supramaximal pain stimulus (claw
      clamp) was applied, and the appearance of a withdrawal reaction was recorded. The
      isoflurane MAC was defined as the end-tidal concentration required to produce a
      50% response rate. At each Xe concentration, the responses to the pain stimulus
      were categorized, and a logistic regression model was fitted to the results to
      determine isoflurane MAC. Isoflurane MAC was decreased by inhalation of Xe in a
      nonlinear manner from 1.92% (95% confidence interval, 1.70%-2.15%) with 0% Xe to
      1.17% (95% confidence interval, 0.75%-1.59%) with 65% Xe. Although this indicates
      partial antagonism of the two anesthetics, a combination of Xe with isoflurane
      may prove valuable for patients requiring a fraction of inspired oxygen more than
      0.3. IMPLICATIONS: We investigated the influence of the anesthetic gas xenon on
      the minimum alveolar anesthetic concentration (MAC) for isoflurane (another
      anesthetic gas). The study was performed in 10 swine ventilated with fixed xenon
      and various concentrations of isoflurane. The isoflurane MAC is decreased by
      inhalation of xenon in a nonlinear relationship.

PMID- 12505937
TI  - The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor
      responses in rats.
AB  - The effects of volatile anesthetics on nonadrenergic, noncholinergic (NANC)
      transmission mediated by calcitonin gene-related peptide (CGRP) are unclear. We
      studied the effects of isoflurane, halothane, and sevoflurane on NANC depressor
      responses to electrical spinal cord stimulation in pithed rats whose mean
      arterial blood pressure was maintained near 120 mm Hg by continuous infusion of
      methoxamine. Autonomic outflow was blocked by hexamethonium. After 30 min of
      inhalation of different concentrations of anesthetics, spinal cord stimulation at
      the lower thoracic level (10 V at 4 Hz; duration, 1 ms) was applied for 30 s to
      induce a NANC depressor response. Isoflurane at 2% and halothane at 1.5%
      attenuated NANC depressor responses significantly, whereas isoflurane at 1%,
      halothane at 0.75%, and sevoflurane at 2% or 4% did not. Volatile anesthetics did
      not attenuate the release of CGRP after spinal cord stimulation, whereas
      isoflurane at 2% and halothane at 1.5% significantly inhibited depressor
      responses to exogenously administered CGRP. Sevoflurane at 4% did not
      significantly affect CGRP-induced depressor responses. Thus, isoflurane and
      halothane at large concentrations attenuate NANC depressor responses by
      attenuating the depressor action of CGRP, not CGRP release. IMPLICATIONS: The
      anesthetics isoflurane and halothane attenuate nonadrenergic, noncholinergic
      depressor responses mediated by calcitonin gene-related peptide in the rat
      without affecting the release of the peptide.

PMID- 12505938
TI  - Propofol-nitrous oxide anesthesia enhances the heart rate response to intravenous
      isoproterenol infusion.
AB  - Heart rate (HR) response to IV atropine is attenuated during propofol-nitrous
      oxide (N(2)O) anesthesia. We studied the effects of propofol-N(2)O anesthesia on
      isoproterenol-induced HR changes. The control group (n = 15) received no propofol
      and no N(2)O. Patients in the propofol-N(2)O group (n = 21) received IV propofol
      2.5 mg/kg over 1 min followed by a continuous infusion of propofol 10 mg x kg(-1)
      x h(-1). After tracheal intubation, anesthesia was maintained with propofol 5 mg.
      kg(-1) x h(-1) and 67% N(2)O in oxygen. All patients in both groups received IV
      isoproterenol at incremental infusion rates (2.5, 5, 7.5, 10, 12.5, 15, and 17.5
      ng x kg(-1) x min(-1) for 2 min at each dose) until HR increased more than 20 bpm
      from baseline values. At the end of each infusion period, hemodynamic data were
      collected. The HR response to isoproterenol 7.5 ng. kg(-1) x min(-1) was
      increased more in the propofol group than in the control group (20 +/- 5 versus
      14 +/- 4 bpm; P < 0.05). During the isoproterenol infusion at 10 ng. kg(-1) x
      min(-1), HR increased by more than 20 bpm in all patients in the propofol group
      but in only 31% of patients in the control group (P < 0.0001). These results
      suggest that continuous isoproterenol infusion might be useful when a large dose
      of atropine is ineffective in restoring normal HR during propofol-N(2)O
      anesthesia. IMPLICATIONS: We demonstrated that the heart rate response to IV
      isoproterenol infusion is enhanced during propofol-nitrous oxide anesthesia. This
      suggests that continuous isoproterenol infusion may be useful when a large dose
      of atropine is ineffective for restoration of normal heart rate in patients
      receiving propofol-nitrous oxide anesthesia.

PMID- 12505939
TI  - The effects of clonidine premedication on the blood pressure and tachycardiac
      responses to ephedrine in elderly and young patients during propofol anesthesia.
AB  - We studied the pressor and tachycardiac responses to ephedrine in elderly and
      young patients given either clonidine or midazolam during propofol anesthesia. In
      the first experiment, elderly (>60 yr) and young (20-45 yr) patients were
      randomly allocated to one of four groups according to age and premedicated
      regimens (n = 16 each; elderly-clonidine [EC], elderly-midazolam [EM], young
      clonidine [YC], and young-midazolam [YM]). Under propofol anesthesia, ephedrine
      was injected, and hemodynamic measurements were made. In the second experiment,
      with clonidine premedication, elderly patients (n = 16) were given a reduced dose
      of propofol (EC-LP) and young patients (n = 16) were given an increased dose of
      propofol (YC-HP). Ephedrine was injected, and he- modynamic measurements were
      performed. The in-creases in mean blood pressure and heart rate were larger in
      the EC group than in the EM, YM, and EC-LP groups (P < 0.05). In the YC-HP group,
      the pressor response to ephedrine tended to be augmented as compared with the YC
      group but was not statistically significant. These results suggest that clonidine
      premedication augmented the pressor and tachycardiac responses to ephedrine,
      especially in elderly patients during a standard dose of propofol anesthesia, and
      that clonidine, age, and propofol could be involved in the augmentation of the
      blood pressure and tachycardiac responses to ephedrine. IMPLICATIONS: Clonidine
      premedication augments the pressor and tachycardiac responses to ephedrine in
      elderly patients during standard or large doses of propofol anesthesia but does
      not augment during small doses of propofol anesthesia. Clonidine, age, and
      propofol could be involved in the augmentation of the pressor and tachycardiac
      responses to ephedrine.

PMID- 12505940
TI  - A manual slide rule for target-controlled infusion of propofol: development and
      evaluation.
AB  - We describe the development and evaluation of a simple slide rule that enables
      the bedside determination of the infusion rate for a particular target plasma
      concentration of propofol. The infusion rate to reach this target concentration
      at time (t) is the product of the target concentration, body weight, and a
      correction factor that depends on the time elapsed from the start of the initial
      infusion. Our target-controlled infusion (TCI) slide rule, constructed along this
      principle, performs the multiplications, analogous to the principle of the
      classical slide rule, as addition of logarithms. We calculated the percentage
      deviation of the predicted concentration obtained by STANPUMP versus predicted
      concentrations obtained using the infusion rates determined from the TCI slide
      rule. The evaluation using STANPUMP simulations showed, for a constant target
      concentration of 3 micro g/mL of propofol, a mean deviation of 4.05% (max, 6.97%)
      in the first 15 min and a mean deviation of 0.5% (max, 2.03%) between 16 and 300
      min. The mean deviation after changing the target from 3 micro g/mL to 1, 2, 4,
      or 5 micro g/mL ranged from 1.15% to 17.76%. This pocket-sized TCI slide rule
      combines the advantages of minimal financial and technical cost with reasonable
      accuracy. IMPLICATIONS: We describe the development and evaluation of a simple
      slide rule that enables the bedside determination of the required infusion rate
      for a particular target plasma concentration. This pocket-sized target-controlled
      infusion slide rule combines the advantages of minimal financial and technical
      cost with reasonable accuracy.

PMID- 12505941
TI  - Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus
      accumbens: a microdialysis study.
AB  - Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the
      actions of various psychotropic and addictive drugs. Ketamine and barbiturates
      have psychotropic effects and addictive properties, but barbiturates prevent
      ketamine's psychotomimetic effects. We investigated the effects of ketamine and
      pentobarbital on dopamine release in the NAC. A microdialysis probe was implanted
      in the NAC in 35 rats, which were randomly assigned to seven groups: a normal
      saline intraperitoneal injection (ip) group, 50 and 100 mg/kg of ketamine ip
      groups, 25 and 50 mg/kg of pentobarbital ip groups, and a normal saline or 25
      mg/kg of pentobarbital ip followed by 50 mg/kg of ketamine ip groups. Perfusate
      samples were collected every 20 min, and dopamine concentration was measured by
      high-performance liquid chromatography. Ketamine at doses of 50 mg/kg and 100
      mg/kg significantly increased dopamine release in the NAC. Conversely,
      pentobarbital significantly decreased dopamine release in the NAC and inhibited
      the ketamine-induced dopamine release. These data suggest that the dopamine
      release in the NAC may be involved in ketamine-induced, but not barbiturate
      induced, psychotropic effects and addiction. Inhibition of ketamine-induced
      dopamine release by barbiturates may be a mechanism by which they prevent
      ketamine emergence reactions. IMPLICATIONS: Ketamine increased dopamine release
      in the nucleus accumbens, which was inhibited by pentobarbital. The mesolimbic
      dopamine system may be involved in the psychotomimetic effects of ketamine, and
      the suppression of ketamine emergence reactions by barbiturates may be because of
      the inhibition of ketamine-induced dopamine release in the nucleus accumbens.

PMID- 12505942
TI  - Extending the skeletal muscle viability period in the malignant hyperthermia
      test.
AB  - The caffeine halothane contracture test (CHCT) is the only validated test for
      diagnosing malignant hyperthermia (MH) susceptibility (MHS) and phenotyping MHS
      families. Although most diagnostic laboratory tests can check intra- and
      interlaboratory consistency through the use of standard control samples, there
      has been no practical way to achieve this goal for the CHCT. The distances
      between diagnostic centers and time constraints of the CHCT protocol (5 h)
      prohibit centers from sharing tissue samples. In this study, we investigated
      varying storage conditions to extend the standard viability period of skeletal
      muscle to 24 h. Twenty MHS patients were tested according to the North America
      protocol. After standard CHCT, the surplus muscle samples were placed in one of
      the following four treatment groups. In Groups 1 and 2, muscles remained under
      tension and were stored in Krebs buffer (pH 7.4) at 23 degrees C-25 degrees C
      (clamped-warm) and 4 degrees C (clamped-cold), respectively. In Groups 3 and 4,
      muscle strips were dissected, and the ends were tied with silk sutures, cut from
      the clamp, and placed in Krebs buffer at 23 degrees C-25 degrees C (free-warm)
      and 4 degrees C (free-cold), respectively. The responses of the treatment groups
      to halothane (3%) and caffeine (0.5-32 mM) were tested at 22-26 h after excision.
      The clamped-warm storage group correctly diagnosed MHS in all patients.
      IMPLICATIONS: Varying conditions for storage of muscle were investigated to
      extend the viability period of muscle in the malignant hyperthermia (MH) test
      from 5 to 24 h. Muscles stored for 24 h under tension at room temperature
      remained viable and correctly diagnosed MH susceptibility in all patients.

PMID- 12505943
TI  - Serum and cerebrospinal fluid concentrations of midazolam after epidural
      administration in dogs.
AB  - The epidural administration of midazolam has analgesic effects that might be
      mediated by gamma-aminobutyric acid type A receptors in the spinal cord. In this
      study, we examined both serum and cerebrospinal fluid (CSF) concentrations of
      midazolam after epidural administration to investigate the possibility of
      midazolam entering CSF directly from the epidural space. Five male mongrel dogs
      had catheters inserted in a femoral artery, the epidural space at L3-4, and the
      intrathecal space at the atlanto-occipital region under general anesthesia.
      Midazolam 1 mg/kg was epidurally administered, and arterial blood and CSF samples
      were collected until 240 min after the midazolam administration to measure
      midazolam concentration. Serum midazolam concentration increased and reached a
      peak at 30 min after the administration (224.8 +/- 30.5 ng/mL) and then decreased
      to 25.8 +/- 6.0 ng/mL at 240 min. Midazolam concentration in the CSF was less
      than the detection limit at 5 min, reached a peak at 30 min after the
      administration (7.2 +/- 4.7 ng/mL), and decreased to 3.6 +/- 3.3 ng/mL at 240
      min. In conclusion, epidurally administered midazolam enters CSF, but CSF
      concentrations are only 3% of those in the systemic circulation. IMPLICATIONS:
      Midazolam, which has spinally mediated analgesic potency, was epidurally
      administered in dogs, and serum and cerebrospinal fluid concentrations were
      measured. Epidurally administered midazolam enters the cerebrospinal fluid, but
      concentrations are only 3% of those in the systemic circulation.

PMID- 12505944
TI  - Bronchospasm induced by propofol in a patient with sick house syndrome.
AB  - IMPLICATIONS: Propofol is often used in patients with asthma, but it can induce
      bronchospasm. We report a patient with sick house syndrome (nonspecific
      complaints of mucosal irritation, headache, nausea, and chest symptoms) who
      suffered bronchospasm. This case suggests that propofol is not always a safe
      anesthetic for patients with asthma, especially drug-induced asthma.

PMID- 12505945
TI  - Delayed onset of malignant hyperthermia in desflurane anesthesia.
AB  - IMPLICATIONS: Animal-experimental studies demonstrate desflurane's trigger effect
      for malignant hyperthermia (MH). In contrast to other anesthetics, the time
      interval from exposure to the occurrence of symptoms is much longer with
      desflurane. This case report focuses on MH induced by desflurane alone.

PMID- 12505946
TI  - An unusual complication of total intravenous anesthesia: mutism.
AB  - IMPLICATIONS: We report a case of mutism secondary to total IV anesthesia with
      propofol, as an unusual complication that we have not found in the literature.

PMID- 12505947
TI  - A comparative study of three warming interventions to determine the most
      effective in maintaining perioperative normothermia.
AB  - Perioperative hypothermia poses a challenge because of its deleterious effects on
      patient recovery. The current practice of applying two cotton blankets on
      patients during surgery is thought to be less ideal than using reflective
      insulation or forced-air warming. We studied 300 patients who underwent
      unilateral total knee replacement and were randomized equally to three groups:
      (a) the two-cotton-blanket group, (b) the one-reflective-blanket with one-cotton
      blanket group, and (c) the forced-air-warming with one-cotton-blanket group.
      Tympanic temperature readings were taken before surgery in the induction room, on
      arrival at the recovery room, and at 10-min intervals until discharge from the
      recovery room. On arrival at the recovery room, the forced-air-warming group had
      significantly higher temperatures (adjusted for sex, age, and patient's induction
      room temperature) of 0.577 degrees C +/- 0.079 degrees C (95% confidence interval
      [CI], 0.427-0.726; P < 0.001) and 0.510 degrees C +/- 0.08 degrees C (95% CI,
      0.349-0.672; P < 0.001) more than the reflective-blanket and two-cot-ton-blanket
      groups, respectively. The forced-air-warming group took a significantly (P <
      0.001) shorter time of 18.75 min (95% CI, 13.88-23.62) to achieve a temperature
      of 36.5 degrees C in the recovery room as compared with 41.78 min (95% CI, 36.86
      46.58) and 36.43 min (95% CI, 31.23-41.62) for the reflective-blanket and two
      cotton-blanket groups, respectively. The reflective technology was less effective
      than using two cotton blankets, and the forced-air warming was most efficient in
      maintaining perioperative normothermia. IMPLICATIONS: Perioperative hypothermia
      has deleterious effects on patient recovery. We found in patients having knee
      surgery that reflective technology was less effective than using two cotton
      blankets, whereas active surface warming with the forced-air method was most
      effective in maintaining normothermia.

PMID- 12505948
TI  - Safe use of pulse oximetry during verteporphin therapy.
AB  - IMPLICATIONS: Pulse oximetry may produce skin damage after the administration of
      photosensitizing chemotherapeutic drugs. Surgery must often be performed in near
      darkness during photodynamic therapy. Limiting the duration of pulse oximetry and
      rotating sites allowed successful use of pulse oximetry in a long anesthetic
      during which verteporphin was administered.

PMID- 12505949
TI  - An intervention study to enhance postoperative pain management.
AB  - This study, conducted before and after the implementation of an acute pain
      service (APS) in a 1000-bed hospital, describes the process of the implementation
      of an APS. The nursing, anesthesia, and surgery departments were involved. In
      this study we sought to evaluate the results of a continuous quality improvement
      program by defining quality indicators and using quality tools. A quality program
      in accordance with current standards of acute pain treatment (multimodal) was
      worked out to enhance pain relief for all surgical inpatients. A survey of
      nurses' knowledge with regard to postoperative pain was conducted, and a visual
      analog scale (VAS) was introduced to assess pain intensity. Both nurses and
      physicians became familiar with evidence-based guidelines concerning
      postoperative pain. The entire process was monitored in three consecutive surveys
      and enrolled 2383 surgical inpatients. Pain indicators based on VAS and analgesic
      consumption were recorded during the first 72 postoperative hours. After a
      baseline survey about current practices of pain treatment, a nurse-based,
      anesthesiologist-supervised APS was implemented. The improvement in pain relief,
      expressed as VAS scores, was assessed in two further surveys. A quality manual
      was written and implemented. A major improvement in pain scores was observed
      after the APS inception (P < 0.001). IMPLICATIONS: The implementation of an acute
      pain service, including pain assessment by a visual analog scale, standard
      multimodal pain treatment, and continuous quality evaluation, improved
      postoperative pain relief. Establishing teams of surgeons, anesthesiologists, and
      nurses is the prerequisite for this improvement.

PMID- 12505950
TI  - Catheter-associated masses in patients receiving intrathecal analgesic therapy.
AB  - A cohort of seven patients receiving intrathecal analgesic drug therapy for
      chronic intractable pain underwent radiocontrast myelography and computed
      tomography (CT) scanning to screen for catheter-associated intrathecal masses.
      Three of seven patients examined had intraspinal masses associated with the tip
      of the drug infusion catheter after a total of 118 mo of therapy. The index case
      presented with exacerbation of neuropathic pain and paralysis of the left lower
      extremity. The two additional cases detected by CT myelography were asymptomatic
      at the time the catheter-associated mass was assessed. The mean duration of
      therapy before diagnosis of the catheter-associated mass was 19.6 mo, with a
      range of 16-25 mo. An intergroup comparison of demographic and treatment
      variables between patients, with and without catheter-associated masses,
      demonstrated that patients with masses were younger and were receiving a larger
      morphine dose than patients without masses. The differences were statistically
      significant (P = 0.05). In one patient with an asymptomatic catheter-associated
      intrathecal mass, regression of the mass was observed after cessation of therapy.
      In a second asymptomatic patient, the mass remained stable over 1 yr of continued
      treatment after substitution of hydromorphone for morphine without interruption
      of therapy. Neither asymptomatic patient has subsequently developed additional
      neurologic findings or injury after detection of occult catheter-associated
      intrathecal masses and clinical intervention. We suggest that all patients
      receiving long-term intrathecal analgesia should undergo periodic radiographic
      surveillance to further define their risk of developing occult catheter
      associated masses and to allow intervention before neurologic injury can develop.
      IMPLICATIONS: Catheter-associated intrathecal masses were detected in three of
      seven patients receiving long-term intrathecal analgesia. In the two asymptomatic
      patients, timely clinical intervention was associated with the avoidance of
      subsequent neurologic injury and spontaneous resolution of one of the occult
      masses.

PMID- 12505951
TI  - Intrathecal ketorolac enhances antinociception from clonidine.
AB  - Although both alpha2-adrenergic agonists and cyclooxygenase inhibitors produce
      analgesia, their exact sites of action and interaction remain unclear. A previous
      report demonstrated a surprising inhibition of antinociception in rats from
      intrathecal clonidine by co-administered ketorolac. There are no other reports of
      interaction between these two classes of analgesics. We therefore reexamined this
      interaction, determining the effect of intrathecal clonidine and ketorolac alone
      and in combination in normal rats. Clonidine, but not ketorolac, produced
      antinociception to noxious hind paw thermal stimulation. The addition of
      ketorolac significantly enhanced the effect of clonidine, indicating a
      synergistic interaction for analgesia. Although the reasons for the discrepancy
      between this and the previous report are unclear, these results are consistent
      with previous studies that indicate an antinociceptive action of intrathecal
      alpha2-adrenergic agonists in the normal condition, a lack of such effect for
      cyclooxygenase inhibitors, and positive reinforcing effects of these two systems
      when co-stimulated. IMPLICATIONS: Spinal injection of the alpha2-adrenergic
      agonist clonidine and the cyclooxygenase inhibitor ketorolac results in a
      synergistic interaction for antinociception in normal animals, suggesting that
      the combination of these drugs will enhance rather than detract from the
      analgesia of either alone.

PMID- 12505952
TI  - Dexmedetomidine fails to cause hyperalgesia after cessation of chronic
      administration.
AB  - Hyperalgesia occurring after the cessation of chronic opioid administration
      occurs in humans and has been modeled in rodents with chronic systemic and
      intrathecal administration paradigms. It is, however, unclear if this type of
      postanalgesic hyperalgesia is unique to opioids. The alpha(2)-adrenergic receptor
      agonist, dexmedetomidine (Dex), is similar to opioids in that it is an analgesic
      that interacts with cell-surface receptors linked to the inhibition of adenylate
      cyclase and the modulation of ion channel activity. In these studies, we first
      constructed antinociceptive dose-response curves for Dex and morphine (MSO4). The
      50% effective doses for Dex and MSO4 administered intraperitoneally to C57Bl/6
      mice were 75 micro g/kg and 5.2 mg/kg, respectively. Using equally effective
      doses, we treated separate groups of mice with twice-daily injections of Dex or
      MSO4 for 5 days. Tolerance to these drugs was documented after this period. In
      the 16-72 h after cessation of administration, MSO4-treated mice demonstrated
      both thermal hyperalgesia and mechanical allodynia. However, the Dex-treated mice
      showed no changes in their thermal or mechanical withdrawal thresholds. We
      conclude that using this experimental paradigm, opioids but not an alpha(2)
      adrenergic agonist, cause hyperalgesia and allodynia after cessation of chronic
      administration. IMPLICATIONS: The cessation of the administration of opioids is
      associated with hyperalgesia in both humans and other animals. However,
      antinociceptive dexmedetomidine does not seem to be associated with this type of
      hyperalgesia syndrome during periods of abstinence.

PMID- 12505953
TI  - Conversion disorder after implant of a spinal cord stimulator in a patient with a
      complex regional pain syndrome.
AB  - IMPLICATIONS: This case history describes the treatment of a patient suffering
      with persistent pain. He was treated surgically with implantation of a spinal
      cord stimulator. After surgery, a partial paralysis that could not be explained
      medically and that was probably related to emotional factors occurred, and
      cognitive behavioral treatment was begun. This paper discusses the importance of
      considering social and psychological factors when medical treatment options are
      considered.

PMID- 12505954
TI  - An updated view of the national anesthesia personnel shortfall.
AB  - Reports of anesthesia personnel shortages in 2001 led to the first comprehensive
      analysis of labor supply and demand for anesthesiologists since 1993. We now
      update this analysis and forecast, incorporating newly available data about
      residency composition, American Board of Anesthesiology and Certified Registered
      Nurse Anesthetist certification, the 2002 residency match, surgical facilities,
      and the US physician workforce. In addition, US residency programs were surveyed;
      national health care utilization and economic data were reviewed. Adjusted for
      the new information, our model still shows an anesthesiologist shortfall in 2002,
      projected to continue through 2005. We now estimate a current shortage of 1100
      3800 anesthesiologists in 2002, on the basis of past service demand growth
      assumptions of 2%-3%, respectively. By 2005 this number is expected to be 500
      3900, depending on a future service demand growth of 1.5%-2%, respectively. To
      avoid a surplus of anesthesiologists in 2006-2010, our model suggests that the
      number of graduates should level out at 1600 yearly, with a 1.5% service demand
      growth. To forecast the anesthesia personnel market more accurately, thereby
      helping supply match demand, substantially better quantification of future demand
      for anesthesia services is needed. If sustained growth in service demand >1.5% is
      likely, entry into the specialty should be encouraged beyond the current level.
      IMPLICATIONS: With updates from training programs, surgical activity, and other
      sources, our previously described model estimates a continuing shortfall of 1000
      3800 anesthesiologists in 2002 and 500-3900 in 2005, assuming that service demand
      growth is 1.5% or 2% annually. If service growth >1.5% is likely, entry into the
      specialty should be encouraged beyond current levels.

PMID- 12505955
TI  - A needle-free jet-injection system with lidocaine for peripheral intravenous
      cannula insertion: a randomized controlled trial with cost-effectiveness
      analysis.
AB  - Insertion of a peripheral IV cannula is a common, although painful, procedure. We
      tested the analgesic efficacy, adverse effects, and cost-effectiveness of a
      needle-free intradermal drug delivery system (Jet) with lidocaine for the
      insertion of an IV cannula (18-gauge; dorsum of hand). Four-hundred patients were
      randomly allocated to one of four groups: (a) no treatment, (b) Jet (J-Tip),
      National Medical Products Inc, CA; $3.0 per device) with 0.5 mL of saline, (3)
      Jet with 0.5 mL of lidocaine 1%, and (4) Jet with 0.5 mL of lidocaine 2%. Pain
      was evaluated using a numerical verbal scale (NVS 0-10). A NVS < or =3 was
      considered as acceptable in this context. Incremental cost-effectiveness ratios
      were calculated. Without treatment, 42.4% of patients had a NVS < or = 3, 39.3%
      with saline, 60.7% with 1% lidocaine (relative risk [RR] compared with no
      treatment, 0.70; 95% confidence interval [CI], 0.53-0.93), and 86.7% with 2%
      lidocaine (RR, 0.49; 95% CI, 0.38-0.62). Nineteen and one-half percent of
      patients had a NVS >3 because of Jet treatment, 13.5% had local hyperemia, and
      16.9% had minor local bleeding. Of all Jet treatments, 10.5% were technical
      failures, and there were 17.6% cannula insertion failures (10.1% without
      treatment [RR, 1.74; 95% CI, 0.92-3.32]). Compared with no treatment, costs to
      generate one additional patient with a NVS < or =3 were $23 with lidocaine 1% and
      $10 with lidocaine 2%. On insertion of an IV cannula on the back of the hand, 58%
      of patients report at least moderate pain. Lidocaine-Jet is analgesic; there is
      dose-responsiveness. However, Jet treatment is not painless, and costs incurred
      to achieve one success compared with doing nothing are not negligible.
      IMPLICATIONS: Insertion of an IV cannula is painful. Four-hundred patients were
      randomly allocated to test the analgesic efficacy, adverse effects, and cost
      effectiveness of the needle-free intradermal drug delivery system (J-Tip); Jet).
      Jet with lidocaine is effective, but its application is not painless. Costs to
      achieve one patient with no more than moderate pain (numerical verbal scale < or
      =3 of 10) on insertion of an IV cannula are $10.

PMID- 12505956
TI  - One-lung ventilation with high tidal volumes and zero positive end-expiratory
      pressure is injurious in the isolated rabbit lung model.
AB  - We tested the hypothesis that one-lung ventilation (OLV) with high tidal volumes
      (VT) and zero positive end-expiratory pressure (PEEP) may lead to ventilator
      induced lung injury. In an isolated, perfused rabbit lung model, VT and PEEP were
      set to avoid lung collapse and overdistension in both lungs, resulting in a
      straight pressure-time (P-vs-t) curve during constant flow. Animals were
      randomized to (a) nonprotective OLV (left lung) (n = 6), with VT values as high
      as before randomization and zero PEEP; (b) protective OLV (left lung) (n = 6),
      with 50% reduction of VT and maintenance of PEEP as before randomization; and (c)
      control group (n = 6), with ventilation of two lungs as before randomization. The
      nonprotective OLV was associated with significantly smaller degrees of collapse
      and overdistension in the ventilated lung (P < 0.001). Peak inspiratory pressure
      values were higher in the nonprotective OLV group (P < 0.001) and increased
      progressively throughout the observation period (P < 0.01). The mean pulmonary
      artery pressure and lung weight gain values, as well as the concentration of
      thromboxane B(2), were comparatively higher in the nonprotective OLV group (P <
      0.05). A ventilatory strategy with VT values as high as those used in the
      clinical setting and zero PEEP leads to ventilator-induced lung injury in this
      model of OLV, but this can be minimized with VT and PEEP values set to avoid lung
      overdistension and collapse. IMPLICATIONS: One-lung ventilation with high tidal
      volumes and zero positive end-expiratory pressure (PEEP) is injurious in the
      isolated rabbit lung model. A ventilatory strategy with tidal volumes and PEEP
      set to avoid lung overdistension and collapse minimizes lung injury during one
      lung ventilation in this model.

PMID- 12505957
TI  - PercuTwist: a new single-dilator technique for percutaneous tracheostomy.
AB  - IMPLICATIONS: PercuTwist is a new technique for percutaneous tracheostomy in that
      stoma dilation is achieved with a unique screwlike dilating device. We describe
      the technique itself and our first clinical experiences with PercuTwist.

PMID- 12505958
TI  - Preconditioning with isoflurane produces dose-dependent neuroprotection via
      activation of adenosine triphosphate-regulated potassium channels after focal
      cerebral ischemia in rats.
AB  - In this study, we determined whether repeated brief isoflurane (Iso) anesthesia
      induces ischemic tolerance to focal cerebral ischemia in a dose-response manner
      and whether the effect is dependent on adenosine triphosphate-regulated potassium
      channels. In Experiment 1, 40 rats were randomly assigned to 4 groups: control
      animals received 100% oxygen 1 h/d for 5 days, whereas the isoflurane (Iso)1,
      Iso2, and Iso3 groups received 0.75%, 1.5%, or 2.25% Iso in oxygen 1 h/d for 5
      days. In Experiment 2, 36 rats were randomly assigned to 4 groups: controls
      received 100% oxygen 1 h/d for 5 days; animals in the Iso and I+G
      (Iso+glibenclamide) groups received 2% Iso in oxygen 1 h/d for 5 days, and the
      I+G group received glibenclamide (GLB) (5 mg/kg intraperitoneally) before each
      Iso pretreatment. Animals in the GLB group received GLB (5 mg/kg
      intraperitoneally) once a day for 5 days. Twenty-four hours after the last
      pretreatment, the right middle cerebral artery was occluded for 120 min.
      Neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 h.
      The NDS and infarct volumes of Iso2 and Iso3 were less than those of the controls
      (P < 0.05). The infarct volume in Iso3 was smaller than in Iso2 (P < 0.05). The
      NDS and infarct volume in the Iso group were less than in the control and I+G
      groups (P < 0.05). There was no statistical difference among the control, I+G,
      and GLB groups. The study demonstrated that repeated Iso anesthesia induces
      ischemic tolerance in rats in a dose-response manner. GLB, an adenosine
      triphosphate-regulated potassium channel blocker, abolished the tolerance induced
      by Iso. IMPLICATIONS: Brief isoflurane anesthesia induces ischemic tolerance in
      the brain. The effect was found to be dose dependent in a rat focal cerebral
      ischemia model. Ischemic tolerance induced by isoflurane preconditioning is
      dependent on activation of adenosine triphosphate-regulated potassium channels.

PMID- 12505959
TI  - S(+)-ketamine attenuates myogenic motor-evoked potentials at or distal to the
      spinal alpha-motoneuron.
AB  - We investigated the effect of S(+)-ketamine on spinal cord evoked potentials
      (ESCPs) and myogenic motor-evoked potentials after electrical stimulation of the
      motor cortex in a rabbit model. This study was designed to characterize the
      relationship between ESCP characteristics and corresponding changes in compound
      muscle action potentials (CMAPs) derived from fore and hind limbs. Direct (D) and
      indirect (I) corticospinal volleys (ESCP) from the upper and lower thoracic
      spinal cord, recorded by two bipolar epidural electrodes, were assessed during IV
      administration of 0.02, 0.05, 0.1, and 0.2 mg. kg(-1) x min(-1) of S(+)-ketamine,
      each before and after neuromuscular blockade (0.4 mg/kg of cisatracurium), in 16
      New Zealand White rabbits after single-pulse bipolar electrical stimulation of
      the motor cortex at 50 (threshold), 60, and 70 V. CMAP amplitudes at fore and
      hind limbs were significantly suppressed (P < 0.01) during infusion at 0.1 and
      0.2 mL x kg(-1) x min(-1), whereas neither corresponding D- nor I-waves were
      altered. Similar findings were obtained during variation of stimulus amplitude
      (50-70 V). Multivariate regression analysis of CMAP amplitudes and various ESCP
      characteristics demonstrated no apparent interparametric association. These
      findings indicate that S(+)-ketamine modulates CMAP independent from
      corticospinal D- and I-wave-mediated facilitation at or distal to the spinal
      alpha-motoneuron. IMPLICATIONS: S(+)-Ketamine combines several anesthetic
      properties suitable for total IV neuroanesthesia, including minimal effects on
      neurophysiological monitoring. Recording of neural and myogenic responses after
      electrical stimulation of the motor cortex indicates that S(+)-ketamine modulates
      myogenic motor-evoked potentials by a peripheral mechanism at or distal to the
      spinal alpha-motoneuron.

PMID- 12505960
TI  - Forearm compartment syndrome from intravenous mannitol extravasation during
      general anesthesia.
AB  - IMPLICATIONS: Complications of IV mannitol administration resulting in
      compartment syndrome may warrant surgical intervention. Compartment syndrome is
      difficult to diagnose in the anesthetized patient. Infusing mannitol in an
      observed IV site permits discontinuation of mannitol before complications ensue.
      Early recognition and surgical intervention averted potential impairment in our
      patient.

PMID- 12505961
TI  - Neurologic complications of 405 consecutive continuous axillary catheters.
AB  - Continuous axillary brachial plexus block may theoretically increase the risk of
      neurologic complications because of catheter-induced mechanical trauma or local
      anesthetic toxicity. In this study, we retrospectively reviewed the frequency of
      complications using current techniques and applications. There were 405
      continuous axillary catheters in 368 patients. A preexisting neurologic condition
      was present in 41 (10.1%) patients, including 30 patients with a preoperative
      ulnar neuropathy. In 305 (75.3%) cases, the axillary catheter was placed to
      facilitate rehabilitation after major elbow surgery. Catheters were typically
      placed postoperatively, after documentation of the patient's normal neurologic
      examination. The local anesthetic infusion contained bupivacaine in 355 (88.7%)
      patients and mepivacaine in 45 (11.1%) patients. The mean infusion rate was 10 +/
      2 mL/h. Catheters remained indwelling for 55 +/- 32 h. In 31 patients, the
      axillary catheter was replaced because of technical problems or inadequate
      analgesia. There were 9 complications in 8 patients for an overall frequency of
      2.2%. Complications included one each of the following: localized infection
      (treated with catheter removal and antibiotics), axillary hematoma, and retained
      catheter fragment requiring surgical excision. In addition, two patients reported
      signs and symptoms of systemic (preseizure) local anesthetic toxicity. Four
      (1.0%) patients reported new neurologic deficits postoperatively. In two
      patients, the neural dysfunction was non-anesthesia related. All four had
      continuous catheters placed after major elbow surgery. We conclude that the risk
      of neurologic complications associated with continuous axillary blockade is
      similar to that of single-dose techniques. IMPLICATIONS: We evaluated the risk of
      neurologic complications in 368 patients undergoing 405 consecutive continuous
      axillary blocks. New neurologic deficits were reported in four patients. This
      series suggests that the risk of neurologic complications associated with
      continuous axillary block is similar to that of single-dose techniques.

PMID- 12505962
TI  - Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery:
      a randomized, double-blinded comparison between levobupivacaine and ropivacaine.
AB  - We compared the onset time and quality of interscalene brachial plexus block
      produced with levobupivacaine and ropivacaine in 50 patients undergoing open
      shoulder surgery randomly allocated to receive 30 mL of 0.5% levobupivacaine (n =
      25) or 0.5% ropivacaine (n = 25) injected through a 20-gauge catheter placed into
      the interscalene sheath using a 18-gauge insulated and stimulating Tuohy
      introducer. The block was also prolonged after surgery using a patient-controlled
      interscalene analgesia with 0.125% levobupivacaine or 0.2% ropivacaine,
      respectively (basal infusion rate, 6 mL/h; bolus, 2 mL; lockout period, 15 min;
      maximum boluses per hour, three). Three patients (two with levobupivacaine [8%]
      and one with ropivacaine [4%]) failed to achieve surgical block within 45 min
      after the injection and were excluded. The onset time of surgical block was 20
      min (10-40 min) with levobupivacaine and 20 min (5-45 min) with ropivacaine (P =
      0.53). Rescue intraoperative analgesia (0.1 mg of fentanyl IV) was required in
      eight patients in each group (34%) (P = 0.99). Forty-two patients completed the
      24-h postoperative infusion (22 with levobupivacaine and 20 with ropivacaine).
      Postoperative analgesia was similarly effective in both groups. Total consumption
      of local anesthetic infused during the first 24 h was 147 mL (144-196 mL) with
      levobupivacaine and 162 mL (144-248 mL) with ropivacaine (P = 0.019), with a
      ratio between boluses received and requested of 0.8 (0.4-1.0) and 0.7 (0.4-1.0),
      respectively (P = 0.004). The degree of motor block of the operated limb was
      deeper with levobupivacaine than ropivacaine when starting postoperative
      analgesia; however, no further differences in degree of motor function were
      observed between the two groups. We conclude that 30 mL of levobupivacaine 0.5%
      induces an interscalene brachial plexus anesthesia of similar onset and intensity
      as the one produced by the same volume and concentration of ropivacaine.
      Postoperative interscalene analgesia with 0.125% levobupivacaine results in
      similar pain relief and recovery of motor function with less volume of local
      anesthetic than with 0.2% ropivacaine. IMPLICATIONS: This prospective,
      randomized, double-blinded study demonstrates that 30 mL of 0.5% levobupivacaine
      produces an interscalene brachial plexus block of similar onset and quality as
      the one produced by the same volume of 0.5% ropivacaine. When prolonging the
      block after surgery, 0.125% levobupivacaine provides adequate pain relief and
      recovery of motor function after open shoulder surgery, with less volume infused
      during the first 24 h after surgery than 0.2% ropivacaine.

PMID- 12505963
TI  - The analgesic effect of interscalene block using clonidine as an analgesic for
      shoulder arthroscopy.
AB  - Used as the sole analgesic, clonidine produces analgesia after central neural
      blockade and intraarticular injection but not after axillary block. In this
      study, we sought to determine whether interscalene clonidine induces analgesia
      for shoulder arthroscopy. Forty patients scheduled for shoulder arthroscopy were
      prospectively included in this double-blinded study. Using a nerve stimulator
      technique, an interscalene catheter was inserted. The patients were randomly
      divided into two groups. The interscalene group (n = 20) received clonidine 150
      micro g in 15 mL of saline through the catheter and 1 mL of subcutaneous saline,
      and the systemic group (n = 20) received 15 mL of saline through the catheter and
      clonidine 150 micro g (1 mL) subcutaneously. All patients underwent general
      anesthesia for surgery. On completion of arthroscopy, all patients received, via
      a patient-controlled analgesia, on demand a bolus of 8 mL of ropivacaine 0.2%
      through the catheter with a 1-h lockout period. Postoperative pain was measured
      every 4 h using the visual analog scale (VAS) for 24 h. Additional postoperative
      analgesia was available with parenteral nalbuphine if required until VAS < 3. VAS
      scores in the recovery room were significantly higher in the systemic group
      compared with the interscalene group (P < 0.0001). Analgesic duration was
      significantly longer in the interscalene group (P < 0.00001), and ropivacaine
      consumption was significantly less than in the systemic group (P < 0.0001). No
      significant difference was observed between groups for nalbuphine consumption.
      Side effects were comparable in the two groups. IMPLICATIONS: Clonidine
      administered via an interscalene catheter enhanced analgesia compared with
      systemic administration. Nevertheless, the adverse effect of clonidine at this
      dose limits its use for routine management for postoperative analgesia.

PMID- 12505964
TI  - Continuous plexus and peripheral nerve blocks for postoperative analgesia.

PMID- 12505965
TI  - Complications after sub-Tenon's eye block.
AB  - IMPLICATIONS: The use of blunt instead of sharp needles for ophthalmic local
      anesthesia techniques has reduced the incidence of injury to intra-orbital
      structures. This case review of complications from blunt needle sub-Tenon's block
      suggests that sight-threatening or even life-threatening complications can still
      occur.

PMID- 12505966
TI  - The endotracheal tube moves more often in obese patients undergoing laparoscopy
      compared with open abdominal surgery.
AB  - We compared the incidence of movements of the endotracheal tube (ETT) within the
      trachea in morbidly obese patients undergoing either laparoscopic or open
      gastroplasty. In a double-blinded, prospective, controlled study, 60 patients
      (body mass index, 35-60 kg/m(2)) were equally allocated to either laparoscopic
      LapBand gastroplasty (study group; Group 1) or open laparotomy gastroplasty
      (control; Group 2), both under standardized general anesthesia. Movements of the
      ETT were assessed with chest auscultation, peak inspiratory pressure, ETCO(2),
      SpO(2), and the Rapiscope at predetermined time points: after intubation
      (baseline values), 5 min before peritoneal inflation in Group 1 and 10 min
      postintubation in Group 2, at maximal abdominal inflation in Group 1 and 20 min
      into the procedure in Group 2, 5 min before and 5 min after changing the
      patient's position from neutral to 10 degrees head up and 10 degrees head down in
      Group 1 and 30 and 40 min into the procedure in Group 2, 2 min after abdominal
      deflation and table repositioning in Group 1 and at 50 min in Group 2, and just
      before extubation in both groups. Twenty-one events of ETT tip movement occurred
      in both groups. The tube moved in 15 (50%) study (laparoscopy) group patients
      compared with 6 (20%) controls (laparotomy; P < 0.05), 12 of the former having
      moved downward either after maximal abdominal insufflation or in association with
      head-down positioning. The tubes of five study group patients (17%) advanced into
      the right bronchus, compared with none in the controls (P < 0.05). All changes in
      position were rectified only by the Rapiscope. IMPLICATIONS: Abdominal
      insufflation and changes in table position lead to more frequent movements of the
      endotracheal tube in obese patients undergoing laparoscopic versus open
      gastroplasty. The Rapiscope identifies all these changes, but not the clinically
      available variables.

PMID- 12505967
TI  - A comparison of a left-sided Broncho-Cath with the torque control blocker univent
      and the wire-guided blocker.
AB  - Lung isolation can be accomplished in two ways: the first, a double-lumen
      endotracheal tube (DLT) and the second, a bronchial blocker (Univent or Arndt
      blocker). Previous studies have found that the DLT and the Univent are comparable
      when providing lung isolation. A new bronchial blocker, the wire-guided
      endobronchial blocker (Arndt blocker), has been introduced. However, there is no
      study to report its effectiveness with lung isolation during elective thoracic
      surgical cases. Therefore, we designed a prospective, randomized trial to compare
      the effectiveness of lung isolation among the 3 endotracheal tubes: the left
      sided DLT Broncho-Cath Group A (n = 16 patients), the torque control blocker
      Univent Group B (n = 16 patients), and the wire-guided Arndt blocker Group C (n =
      32 patients). The following variables were recorded: 1) time to initially
      position the assigned tube, 2) frequency of malpositions, 3) frequency of use of
      fiberoptic bronchoscope, 4) overall surgical exposure, and 5) tube acquisition
      cost. The Arndt blocker took longer to place (3:34 min/s) compared with the other
      2 groups: the DLT group (2:08 min/s) or the Univent group (2:38 min/s) (P <
      0.0004). There was no statistical difference in tube malpositions among the three
      groups: two for the DLT group, four for the Univent group, and nine in the Arndt
      group. Excluding the time for tube placement, the Arndt group also took longer
      for the lung to collapse (26:02 min/s), compared with the DLT group (17:54 min/s)
      or Univent group (19:28 min/s) (P < 0.0060). Furthermore, unlike the other two
      groups, the majority of the Arndt patients required suction to achieve lung
      collapse. Once lung isolation was achieved, overall surgical exposure was rated
      excellent for the three groups. Acquisition cost for the DLT group was $1663.20
      (21 tubes opened), $2329.00 for the Univent group (17 tubes opened), and $3567.00
      for the Arndt group (33 wire-guided blockers opened). This study demonstrates
      that the Arndt blocker takes longer to position and longer to deflate the
      isolated lung. For elective thoracic surgical cases, once the lung was isolated,
      the management seemed to be similar for all three tube groups. IMPLICATIONS: We
      compared the latest design of double-lumen tubes Broncho-Cath, Univent, and Arndt
      blockers during lung isolation. Our results show that the Arndt blocker takes
      longer to position and longer to deflate the isolated lung. Once the lung was
      isolated, the management seemed to be similar for all three devices.

PMID- 12505968
TI  - Advancing the tracheal tube over a flexible fiberoptic bronchoscope by a sleeve
      mounted on the insertion cord.
AB  - The advancement of an endotracheal tube (ETT) over a flexible fiberoptic
      bronchoscope (FOB) is often impeded at the glottis. This is attributed to the
      creation of a cleft by the difference in the outer diameter of the fiberscope and
      the internal diameter of the tube. We designed a conical-shaped polyvinyl
      chloride sleeve to fit the insertion cord. This report compares the ease of
      advancement of the tube over a sleeved versus a nonsleeved bronchoscope. General
      anesthesia was induced, and one anesthesiologist introduced the FOB (a 3.8-mm
      Olympus LF2). Patients were randomly assigned to undergo tracheal intubation with
      the regular bronchoscope (25 patients) or the sleeved bronchoscope (25 patients).
      The FOB was advanced to approximately 1 cm above the carina. A blinded operator
      advanced the tube over the bronchoscope. The ETT was successfully advanced over
      the nonsleeved bronchoscope into the trachea on the first attempt in 64% of the
      patients, whereas tracheal intubation succeeded from the first attempt in 96% of
      patients when the sleeved FOB was used (P < 0.05). Advancement of the ETT over
      the fiberscope can be facilitated by using a conically shaped sleeve mounted on
      the insertion cord. IMPLICATIONS: This report shows that a conical sleeve mounted
      on the insertion cord of a fiberoptic bronchoscope will facilitate advancing the
      endotracheal tube into the trachea.

PMID- 12505969
TI  - Lidocaine sprayed down the endotracheal tube attenuates the airway-circulatory
      reflexes by local anesthesia during emergence and extubation.
AB  - To determine whether lidocaine sprayed down the endotracheal tube (ETT) would
      attenuate airway-circulatory reflexes during emergence, we compared the reflex
      responses after endotracheal or IV lidocaine (IVL) in 75 patients receiving a
      standardized anesthetic protocol. At the end of surgery, the patients were
      divided into 3 groups (n = 25 for each group) and given no drug (Group 1), given
      1 mg/kg of 2% lidocaine sprayed down the ETT 5 min before (Group 2), or given the
      same dose of IVL 3 min before extubation (Group 3). Blood pressure and heart rate
      were recorded at predetermined time points from 5 min (baseline) before until 5
      min after extubation. The number of coughs per patient was continuously monitored
      during this period. The number (mean +/- SD) of coughs was decreased in Group 2
      (4.5 +/- 3.7) compared with the control (10.2 +/- 6.0) (P < 0.01) with no
      difference for the control versus Group 3 (7.8 +/- 4.6). The increase in blood
      pressure was only attenuated immediately before extubation (P < 0.05), whereas
      the increase in heart rate was attenuated (P < 0.05) at all (except baseline)
      time points (P < 0.05) in Group 2 compared with the control with no difference
      for the control versus Group 3. The results indicate that lidocaine sprayed down
      the ETT suppresses the reflexes whereas using the same dose IVL does not, which
      is probably attributable to the mucosa-anesthetizing effect of lidocaine.
      IMPLICATIONS: Lidocaine sprayed down the endotracheal tube suppresses the airway
      circulatory reflex responses whereas using the same dose IV lidocaine does not.
      This effect seems to be from the direct local anesthesia rather than from
      systemic absorption from the airway.

PMID- 12505970
TI  - Endobronchial high-frequency jet ventilation for endobronchial laser surgery: an
      alternative approach.
AB  - IMPLICATIONS: We describe a technique of one-lung high-frequency jet ventilation
      surgery with continuous monitoring of airway pressures that achieves satisfactory
      operating conditions with less complications than other similar approaches.

PMID- 12505971
TI  - Anaphylactoid reaction to cisatracurium may be explained by atracurium
      metabolites.

PMID- 12505972
TI  - Central venous catheter tip and perforation.

PMID- 12505973
TI  - Arterial hypotension during induction of anesthesia may not be a risk factor for
      postoperative nausea and vomiting.

PMID- 12505974
TI  - Airway management for pediatric esophagogastroduodenoscopy using an endoscopy
      mask.

PMID- 12505975
TI  - Posterior approach to popliteal block.

PMID- 12505976
TI  - Aide-memoir to pharyngeal pack removal.

PMID- 12505977
TI  - The insidiousness of brain retractor pressure: another "Smoking gun"?

PMID- 12505978
TI  - The relationship between shear rate and vessel diameter.

PMID- 12505979
TI  - Structural insights into ligand interactions at the acetylcholinesterase
      peripheral anionic site.
AB  - The peripheral anionic site on acetylcholinesterase (AChE), located at the active
      center gorge entry, encompasses overlapping binding sites for allosteric
      activators and inhibitors; yet, the molecular mechanisms coupling this site to
      the active center at the gorge base to modulate catalysis remain unclear. The
      peripheral site has also been proposed to be involved in heterologous protein
      associations occurring during synaptogenesis or upon neurodegeneration. A novel
      crystal form of mouse AChE, combined with spectrophotometric analyses of the
      crystals, enabled us to solve unique structures of AChE with a free peripheral
      site, and as three complexes with peripheral site inhibitors: the
      phenylphenanthridinium ligands, decidium and propidium, and the pyrogallol
      ligand, gallamine, at 2.20-2.35 A resolution. Comparison with structures of AChE
      complexes with the peptide fasciculin or with organic bifunctional inhibitors
      unveils new structural determinants contributing to ligand interactions at the
      peripheral site, and permits a detailed topographic delineation of this site.
      Hence, these structures provide templates for designing compounds directed to the
      enzyme surface that modulate specific surface interactions controlling catalytic
      activity and non-catalytic heterologous protein associations.

PMID- 12505980
TI  - Control of protein life-span by N-terminal methionine excision.
AB  - Peptide deformylases (PDFs) have been discovered recently in eukaryotic genomes,
      and it appears that N-terminal methionine excision (NME) is a conserved pathway
      in all compartments where protein synthesis occurs. This work aimed at uncovering
      the function(s) of NME in a whole proteome, using the chloroplast-encoded
      proteins of both Arabidopsis thaliana and Chlamydomonas reinhardtii as model
      systems. Disruption of PDF1B in A.thaliana led to an albino phenotype, and an
      extreme sensitivity to the PDF- specific inhibitor actinonin. In contrast, a
      knockout line for PDF1A exhibited no apparent phenotype. Photosystem II activity
      in C.reinhardtii cells was substantially reduced by the presence of actinonin.
      Pulse-chase experiments revealed that PDF inhibition leads to destabilization of
      a crucial subset of chloroplast-encoded photosystem II components in C.
      reinhardtii. The same proteins were destabilized in pdf1b. Site-directed
      substitutions altering NME of the most sensitive target, subunit D2, resulted in
      similar effects. Thus, plastid NME is a critical mechanism specifically
      influencing the life-span of photosystem II polypeptides. A general role of NME
      in modulating the half-life of key subsets of proteins is suggested.

PMID- 12505981
TI  - Directed evolution of an extremely fast phosphotriesterase by in vitro
      compartmentalization.
AB  - We describe the selection of a phosphotriesterase with a very fast k(cat) (over
      10(5) s(-1)), 63 times higher than the already very efficient wild-type enzyme.
      The enzyme was selected from a library of 3.4 x 10(7) mutated phosphotriesterase
      genes using a novel strategy based on linking genotype and phenotype by in vitro
      compartmentalization (IVC) using water-in-oil emulsions. First, microbeads, each
      displaying a single gene and multiple copies of the encoded protein, are formed
      by compartmentalized in vitro translation. These microbeads can then be selected
      for catalysis or binding. To select for catalysis the microbeads are re
      emulsified in a reaction buffer of choice with a soluble substrate. The product
      and any unreacted substrate are coupled to the beads when the reaction is
      finished. Product-coated beads, displaying active enzymes and the genes that
      encode them, are detected with anti-product antibodies and selected using flow
      cytometry. This completely in vitro process selects for all enzymatic features
      simultaneously (substrate recognition, product formation, rate acceleration and
      turnover) and single enzyme molecules can be detected.

PMID- 12505982
TI  - Domain organization of the MscS mechanosensitive channel of Escherichia coli.
AB  - The major structural features of the Escherichia coli MscS mechanosensitive
      channel protein have been explored using alkaline phosphatase (PhoA) fusions,
      precise deletions and site-directed mutations. PhoA protein fusion data, combined
      with the positive-inside rule, strongly support a model in which MscS crosses the
      membrane three times, adopting an N(out)-C(in) configuration. Deletion data
      suggest that the C-terminal domain of the protein is essential for the stability
      of the MscS channel, whereas the protein will tolerate small deletions at the N
      terminus. Four mutants that exhibit either gain-of-function (GOF) or loss-of
      function have been identified: a double mutation I48D/S49P inactivates MscS,
      whereas the MscS mutants T93R, A102P and L109S cause a strong GOF phenotype. The
      similarity of MscS to the last two domains of MscK (formerly KefA) is reinforced
      by the demonstration that expression of a truncated MscK protein can substitute
      for MscL and MscS in downshock survival assays. The data derived from studies of
      the organization, conservation and the influence of mutations provide significant
      insights into the structure of the MscS channel.

PMID- 12505983
TI  - Cathepsin A regulates chaperone-mediated autophagy through cleavage of the
      lysosomal receptor.
AB  - Protective protein/cathepsin A (PPCA) has a serine carboxypeptidase activity of
      unknown physiological function. We now demonstrate that this protease activity
      triggers the degradation of the lysosome-associated membrane protein type 2a
      (lamp2a), a receptor for chaperone-mediated autophagy (CMA). Degradation of
      lamp2a is important because its level in the lysosomal membrane is a rate
      limiting step of CMA. Cells defective in PPCA show reduced rates of lamp2a
      degradation, higher levels of lamp2a and higher rates of CMA. Restoration of PPCA
      protease activity increases rates of lamp2a degradation, reduces levels of
      lysosomal lamp2a and reduces rates of CMA. PPCA associates with lamp2a on the
      lysosomal membrane and cleaves lamp2a near the boundary between the luminal and
      transmembrane domains. In addition to the well-studied role of PPCA in targeting
      and protecting two lysosomal glycosidases, we have defined a role for the
      proteolytic activity of this multifunctional protein.

PMID- 12505984
TI  - Pseudomonas type III effector AvrPtoB induces plant disease susceptibility by
      inhibition of host programmed cell death.
AB  - The AvrPtoB type III effector protein is conserved among diverse genera of plant
      pathogens suggesting it plays an important role in pathogenesis. Here we report
      that Pseudomonas AvrPtoB acts inside the plant cell to inhibit programmed cell
      death (PCD) initiated by the Pto and Cf9 disease resistance proteins and,
      remarkably, the pro-apoptotic mouse protein Bax. AvrPtoB also suppressed PCD in
      yeast, demonstrating that AvrPtoB functions as a cell death inhibitor across
      kingdoms. Using truncated AvrPtoB proteins, we identified distinct N- and C
      terminal domains of AvrPtoB that are sufficient for host recognition and PCD
      inhibition, respectively. We also identified a novel resistance phenotype, Rsb,
      that is triggered by an AvrPtoB truncation disrupted in the anti-PCD domain. A
      Pseudomonas syringae pv. tomato DC3000 strain with a chromosomal mutation in the
      AvrPtoB C-terminus elicited Rsb-mediated immunity in previously susceptible
      tomato plants and disease was restored when full-length AvrPtoB was expressed in
      trans. Thus, our results indicate that a type III effector can induce plant
      susceptibility to bacterial infection by inhibiting host PCD.

PMID- 12505985
TI  - Repeat motifs of tau bind to the insides of microtubules in the absence of taxol.
AB  - The tau family of microtubule-associated proteins has a microtubule-binding
      domain which includes three or four conserved sequence repeats. Pelleting assays
      show that when tubulin and tau are co- assembled into microtubules, the presence
      of taxol reduces the amount of tau incorporated. In the absence of taxol, strong
      binding sites for tau are filled by one repeat motif per tubulin dimer;
      additional tau molecules bind more weakly. We have labelled a repeat motif with
      nanogold and used three-dimensional electron cryomicroscopy to compare images of
      microtubules assembled with labelled or unlabelled tau. With kinesin motor
      domains bound to the microtubule outer surface to distinguish between alpha- and
      beta-tubulin, we show that the gold label lies on the inner surface close to the
      taxol binding site on beta-tubulin. Loops within the repeat motifs of tau have
      sequence similarity to an extended loop which occupies a site in alpha-tubulin
      equivalent to the taxol-binding pocket in beta-tubulin. We propose that loops in
      bound tau stabilize microtubules in a similar way to taxol, although with lower
      affinity so that assembly is reversible.

PMID- 12505986
TI  - Divalent interaction of the GGAs with the Rabaptin-5-Rabex-5 complex.
AB  - Cargo transfer from trans-Golgi network (TGN)-derived transport carriers to
      endosomes involves a still undefined set of tethering/fusion events. Here we
      analyze a molecular interaction that may play a role in this process. We
      demonstrate that the GGAs, a family of Arf-dependent clathrin adaptors involved
      in selection of TGN cargo, interact with the Rabaptin-5-Rabex-5 complex, a
      Rab4/Rab5 effector regulating endosome fusion. These interactions are bipartite:
      GGA-GAE domains recognize an FGPLV sequence (residues 439-443) in a predicted
      random coil of Rabaptin-5 (a sequence also recognized by the gamma1- and gamma2
      adaptin ears), while GGA-GAT domains bind to the C-terminal coiled-coils of
      Rabaptin-5. The GGA-Rabaptin-5 interaction decreases binding of clathrin to the
      GGA-hinge domain, and expression of green fluorescent protein (GFP)-Rabaptin-5
      shifts the localization of endogenous GGA1 and associated cargo to enlarged early
      endosomes. These observations thus identify a binding sequence for GAE/gamma
      adaptin ear domains and reveal a functional link between proteins regulating TGN
      cargo export and endosomal tethering/fusion events.

PMID- 12505987
TI  - PBX1 nuclear export is regulated independently of PBX-MEINOX interaction by PKA
      phosphorylation of the PBC-B domain.
AB  - The regulation of PBC protein function through subcellular distribution is a
      crucial evolutionarily conserved mechanism for appendage patterning. We
      investigated the processes controlling PBX1 nuclear export. Here we show that in
      the absence of MEINOX proteins nuclear export is not a default pathway for PBX1
      subcellular localization. In different cell backgrounds, PBX1 can be imported or
      exported from the nucleus independently of its capacity to interact with MEINOX
      proteins. The cell context-specific balance between nuclear export and import of
      PBX1 is controlled by the PBC-B domain, which contains several conserved serine
      residues corresponding to phosphorylation sites for Ser/Thr kinases. PBX1
      subcellular localization correlates with the phosphorylation state of these
      residues whose dephosphorylation induces nuclear export. Protein kinase A (PKA)
      specifically phosphorylates PBX1 at these serines, and stimulation of endogenous
      PKA activity in vivo blocks PBX1 nuclear export in distal limb mesenchymal cells.
      Our results reveal a novel mechanism for the control of PBX1 nuclear export in
      addition to the absence of MEINOX protein, which involves the inhibition of PKA
      mediated phosphorylation at specific sites within the PBC-B domain.

PMID- 12505988
TI  - Knockout of 'metal-responsive transcription factor' MTF-1 in Drosophila by
      homologous recombination reveals its central role in heavy metal homeostasis.
AB  - 'Metal-responsive transcription factor-1' (MTF-1), a zinc finger protein, is
      conserved from mammals to insects. In the mouse, it activates metallothionein
      genes and other target genes in response to several cell stress conditions,
      notably heavy metal load. The knockout of MTF-1 in the mouse has an embryonic
      lethal phenotype accompanied by liver degeneration. Here we describe the targeted
      disruption of the MTF-1 gene in Drosophila by homologous recombination. Unlike
      the situation in the mouse, knockout of MTF-1 in Drosophila is not lethal. Flies
      survive well under laboratory conditions but are sensitive to elevated
      concentrations of copper, cadmium and zinc. Basal and metal-induced expression of
      Drosophila metallothionein genes MtnA (Mtn) and MtnB (Mto), and of two new
      metallothionein genes described here, MtnC and MtnD, is abolished in MTF-1
      mutants. Unexpectedly, MTF-1 mutant larvae are sensitive not only to copper load
      but also to copper depletion. In MTF-1 mutants, copper depletion prevents
      metamorphosis and dramatically extends larval development/lifespan from normally
      4-5 days to as many as 32 days, possibly reflecting the effects of impaired
      oxygen metabolism. These findings expand the roles of MTF-1 in the control of
      heavy metal homeostasis.

PMID- 12505989
TI  - Protein kinase D mediates a stress-induced NF-kappaB activation and survival
      pathway.
AB  - The activation of the transcription factor NF-kappaB is critical for a number of
      physiological responses. Here, we provide evidence for a signaling pathway that
      mediates NF-kappaB activation in response to oxidative stress. We show that
      tyrosine phosphorylation of protein kinase D (PKD) at Y463 in the Pleckstrin
      Homology (PH) domain is mediated by the Src and Abl tyrosine kinase signaling
      pathway, and that this is both necessary and sufficient to activate NF-kappaB in
      response to oxidative stress. PKD activates NF-kappaB through the IKK complex and
      more specifically, IKKbeta, leading to I(kappa)B(alpha) degradation. We also
      present evidence that this pathway is required for increased cellular survival in
      response to oxidative stress. We propose a model in which protection from
      oxidative stress-induced cell death requires the tyrosine phosphorylation of PKD
      leading to the activation of the transcription factor NF-kappaB.

PMID- 12505990
TI  - RelB is required for Peyer's patch development: differential regulation of p52
      RelB by lymphotoxin and TNF.
AB  - Targeted disruption of the Rel/NF-kappaB family members NF-kappaB2, encoding
      p100/p52, and RelB in mice results in anatomical defects of secondary lymphoid
      tissues. Here, we report that development of Peyer's patch (PP)-organizing
      centers is impaired in both NF-kappaB2- and RelB-deficient animals. IL-7-induced
      expression of lymphotoxin (LT) in intestinal cells, a crucial step in PP
      development, is not impaired in RelB-deficient embryos. LTbeta receptor (LTbetaR)
      deficient mice also lack PPs, and we demonstrate that LTbetaR signaling induces
      p52-RelB and classical p50-RelA heterodimers, while tumor necrosis factor (TNF)
      activates only RelA. LTbetaR-induced binding of p52-RelB requires the degradation
      of the inhibitory p52 precursor, p100, which is mediated by the NF-kappaB
      inducing kinase (NIK) and the IkappaB kinase (IKK) complex subunit IKKalpha, but
      not IKKbeta or IKKgamma. Activation of RelA requires all three IKK subunits, but
      is independent of NIK. Finally, we show that TNF increases p100 levels, resulting
      in the specific inhibition of RelB DNA binding via the C-terminus of p100. Our
      data indicate an important role of p52-RelB heterodimers in lymphoid organ
      development downstream of LTbetaR, NIK and IKKalpha.

PMID- 12505991
TI  - Ablation of telomerase and telomere loss leads to cardiac dilatation and heart
      failure associated with p53 upregulation.
AB  - Cardiac failure is a frequent cause of death in the aging human population.
      Telomere attrition occurs with age, and is proposed to be causal for the aging
      process. To determine whether telomere shortening leads to a cardiac phenotype,
      we studied heart function in the telomerase knockout mouse, Terc-/-. We studied
      Terc-/- mice at the second, G2, and fifth, G5, generation. Telomere shortening in
      G2 and G5 Terc-/- mice was coupled with attenuation in cardiac myocyte
      proliferation, increased apoptosis and cardiac myocyte hypertrophy. On a single
      cell basis, telomere shortening was coincidental with increased expression of
      p53, indicating the presence of dysfunctional telomeres in cardiac myocytes from
      G5 Terc-/- mice. The impairment in cell division, the enhanced cardiac myocyte
      death and cellular hypertrophy, are concomitant with ventricular dilation,
      thinning of the wall and cardiac dysfunction. Thus, inhibition of cardiac myocyte
      replication provoked by telomere shortening, results in de-compensated eccentric
      hypertrophy and heart failure in mice. Telomere shortening with age could also
      contribute to cardiac failure in humans, opening the possibility for new
      therapies.

PMID- 12505992
TI  - Stable co-existence of separate replicons in Escherichia coli is dependent on
      once-per-cell-cycle initiation.
AB  - DNA replication in most organisms is regulated such that all chromosomes are
      replicated once, and only once, per cell cycle. In rapidly growing Escherichia
      coli, replication of eight identical chromosomes is initiated essentially
      simultanously, each from the same origin, oriC. Plasmid-borne oriC sequences
      (minichromosomes) are also initiated in synchrony with the eight chromosomal
      origins. We demonstrate that specific inactivation of newly formed,
      hemimethylated origins (sequestration) was required for the stable co-existence
      of oriC-dependent replicons. Cells in which initiations were not confined to a
      short interval in the cell cycle (carrying mutations in sequestration or
      initiation genes or expressing excess initiator protein) could not support stable
      co-existence of several oriC-dependent replicons. The results show that such
      stable co-existence of oriC-dependent replicons is dependent on both a period of
      sequestration that is longer than the initiation interval and a reduction of the
      initiation potential during the sequestration period. These regulatory
      requirements are the same as those required to confine initiation of each
      replicon to once, and only once, per cell cycle.

PMID- 12505993
TI  - Structure of the topoisomerase VI-B subunit: implications for type II
      topoisomerase mechanism and evolution.
AB  - Type IIA and type IIB topoisomerases each possess the ability to pass one DNA
      duplex through another in an ATP-dependent manner. The role of ATP in the strand
      passage reaction is poorly understood, particularly for the type IIB
      (topoisomerase VI) family. We have solved the structure of the ATP-binding
      subunit of topoisomerase VI (topoVI-B) in two states: an unliganded monomer and a
      nucleotide-bound dimer. We find that topoVI-B is highly structurally homologous
      to the entire 40-43 kDa ATPase region of type IIA topoisomerases and MutL
      proteins. Nucleotide binding to topoVI-B leads to dimerization of the protein and
      causes dramatic conformational changes within each protomer. Our data demonstrate
      that type IIA and type IIB topoisomerases have descended from a common ancestor
      and reveal how ATP turnover generates structural signals in the reactions of both
      type II topoisomerase families. When combined with the structure of the A subunit
      to create a picture of the intact topoisomerase VI holoenzyme, the ATP-driven
      motions of topoVI-B reveal a simple mechanism for strand passage by the type IIB
      topoisomerases.

PMID- 12505994
TI  - Xeroderma pigmentosum group C protein interacts physically and functionally with
      thymine DNA glycosylase.
AB  - The XPC-HR23B complex recognizes various helix-distorting lesions in DNA and
      initiates global genome nucleotide excision repair. Here we describe a novel
      functional interaction between XPC-HR23B and thymine DNA glycosylase (TDG), which
      initiates base excision repair (BER) of G/T mismatches generated by spontaneous
      deamination of 5-methylcytosine. XPC-HR23B stimulated TDG activity by promoting
      the release of TDG from abasic sites that result from the excision of mismatched
      T bases. In the presence of AP endonuclease (APE), XPC-HR23B had an additive
      effect on the enzymatic turnover of TDG without significantly inhibiting the
      subsequent action of APE. Our observations suggest that XPC-HR23B may participate
      in BER of G/T mismatches, thereby contributing to the suppression of spontaneous
      mutations that may be one of the contributory factors for the promotion of
      carcinogenesis in xeroderma pigmentosum genetic complementation group C patients.

PMID- 12505995
TI  - Regulation of shoot epidermal cell differentiation by a pair of homeodomain
      proteins in Arabidopsis.
AB  - In higher plants, the outermost cell layer (L1) of the shoot apex gives rise to
      the epidermis of shoot organs. Our previous study demonstrated that an 8-bp motif
      named the L1 box functions as a cis-regulatory element for L1-specific gene
      expression in the shoot system of Arabidopsis: We show here that PROTODERMAL
      FACTOR2 (PDF2), a member of the HD-GL2 class of homeobox genes, is expressed
      exclusively in the L1 of shoot meristems and that recombinant PDF2 protein
      specifically binds to the L1 box in vitro. Although knockout mutants of PDF2 and
      ATML1, another L1-specific HD-GL2 class gene sharing the highest homology with
      PDF2, display normal shoot development, the double mutant results in severe
      defects in shoot epidermal cell differentiation. This suggests that PDF2 and
      ATML1 are functionally interchangeable and play a critical role in maintaining
      the identity of L1 cells, possibly by interacting with their L1 box and those of
      downstream target-gene promoters.

PMID- 12505996
TI  - The RADICLELESS1 gene is required for vascular pattern formation in rice.
AB  - The molecular mechanisms through which the complex patterns of plant vascular
      tissues are established are largely unknown. The highly ordered, yet simple,
      striate array of veins of rice leaves represents an attractive system to study
      the dynamics underlying pattern formation. Here we show that mutation in the
      RADICLELESS1 (RAL1) gene results in distinctive vascular pattern defects. In ral1
      embryonic scutella, secondary veins are absent and in the prematurely aborted and
      discontinuous primary veins, cells are misaligned to each other. In ral1 leaves,
      longitudinal and commissural (transverse) veins display altered spacing and the
      commissural veins additionally show atypical branching and interruptions in their
      continuity. The vascular pattern alterations of ral1 occur in the context of
      normally shaped leaf primordia. Anatomical inspection and analysis of the
      expression of the procambium specification marker Oshox1-GUS and of the auxin
      inducible reporter DR5-GUS demonstrates that all the vascular patterning
      aberrations of ral1 originate from defects in the procambium, which represents
      the earliest identifiable stage of vascular development. Furthermore, the ral1
      mutant is unique in that procambium formation in leaf primordium development is
      delayed. Finally, the ral1 vascular patterning distortions are associated with a
      defective response to auxin and with an enhanced sensitivity to cytokinin. ral1
      is the first mutant impaired in both procambium development and vascular
      patterning to be isolated in a monocot species.

PMID- 12505997
TI  - Discovery of genes with highly restricted expression patterns in the Drosophila
      wing disc using DNA oligonucleotide microarrays.
AB  - The Drosophila wing disc is divided along the proximal-distal axis into regions
      giving rise to the body wall (proximal), wing hinge (central) and wing blade
      (distal). We applied DNA microarray analysis to discover genes with potential
      roles in the development of these regions. We identified a set of 94 transcripts
      enriched (two fold or greater) in the body wall and 56 transcripts enriched in
      the wing/hinge region. Transcripts that are known to have highly restricted
      expression patterns, such as pannier, twist and Bar-H1 (body wall) and knot,
      nubbin and Distal-less (wing/hinge), showed strong differential expression on the
      arrays. In situ hybridization for 50 previously uncharacterized genes similarly
      revealed that transcript enrichment identified by the array analysis was
      consistent with the observed spatial expression. There was a broad spectrum of
      patterns, in some cases suggesting that the genes could be targets of known
      signaling pathways. We show that three of these genes respond to wingless
      signaling. We also discovered genes likely to play specific roles in tracheal and
      myoblast cell types, as these cells are part of the body wall fragment. In
      summary, the identification of genes with restricted expression patterns using
      whole genome profiling suggests that many genes with potential roles in wing disc
      development remain to be characterized.

PMID- 12505998
TI  - Roles of myosin phosphatase during Drosophila development.
AB  - Myosins are a superfamily of actin-dependent molecular motor proteins, among
      which the bipolar filament forming myosins II have been the most studied. The
      activity of smooth muscle/non-muscle myosin II is regulated by phosphorylation of
      the regulatory light chains, that in turn is modulated by the antagonistic
      activity of myosin light chain kinase and myosin light chain phosphatase. The
      phosphatase activity is mainly regulated through phosphorylation of its myosin
      binding subunit MYPT. To identify the function of these phosphorylation events,
      we have molecularly characterized the Drosophila homologue of MYPT, and analyzed
      its mutant phenotypes. We find that Drosophila MYPT is required for cell sheet
      movement during dorsal closure, morphogenesis of the eye, and ring canal growth
      during oogenesis. Our results indicate that the regulation of the phosphorylation
      of myosin regulatory light chains, or dynamic activation and inactivation of
      myosin II, is essential for its various functions during many developmental
      processes.

PMID- 12505999
TI  - Mitochondrial respiration and Ca2+ waves are linked during fertilization and
      meiosis completion.
AB  - Fertilization increases both cytosolic Ca(2+) concentration and oxygen
      consumption in the egg but the relationship between these two phenomena remains
      largely obscure. We have measured mitochondrial oxygen consumption and the
      mitochondrial NADH concentration on single ascidian eggs and found that they
      increase in phase with each series of meiotic Ca(2+) waves emitted by two
      pacemakers (PM1 and PM2). Oxygen consumption also increases in response to
      Ins(1,4,5)P(3)-induced Ca(2+) transients. Using mitochondrial inhibitors we show
      that active mitochondria sequester cytosolic Ca(2+) during sperm-triggered Ca(2+)
      waves and that they are strictly necessary for triggering and sustaining the
      activity of the meiotic Ca(2+) wave pacemaker PM2. Strikingly, the activity of
      the Ca(2+) wave pacemaker PM2 can be restored or stimulated by flash photolysis
      of caged ATP. Taken together our observations provide the first evidence that, in
      addition to buffering cytosolic Ca(2+), the egg's mitochondria are stimulated by
      Ins(1,4,5)P(3)-mediated Ca(2+) signals. In turn, mitochondrial ATP production is
      required to sustain the activity of the meiotic Ca(2+) wave pacemaker PM2.

PMID- 12506000
TI  - The actin-binding protein UNC-115 is an effector of Rac signaling during axon
      pathfinding in C. elegans.
AB  - Rac GTPases control cell shape by regulating downstream effectors that influence
      the actin cytoskeleton. UNC-115, a putative actin-binding protein similar to
      human abLIM/limatin, has previously been implicated in axon pathfinding. We have
      discovered the role of UNC-115 as a downstream cytoskeletal effector of Rac
      signaling in axon pathfinding. We show that unc-115 double mutants with ced-10
      Rac, mig-2 Rac or unc-73 GEF but not with rac-2/3 Rac displayed synthetic axon
      pathfinding defects, and that loss of unc-115 function suppressed the formation
      of ectopic plasma membrane extensions induced by constitutively-active rac-2 in
      neurons. Furthermore, we show that UNC-115 can bind to actin filaments. Thus, UNC
      115 is an actin-binding protein that acts downstream of Rac signaling in axon
      pathfinding.

PMID- 12506001
TI  - SUPERWOMAN1 and DROOPING LEAF genes control floral organ identity in rice.
AB  - We analyzed recessive mutants of two homeotic genes in rice, SUPERWOMAN1 (SPW1)
      and DROOPING LEAF (DL). The homeotic mutation spw1 transforms stamens and
      lodicules into carpels and palea-like organs, respectively. Two spw1 alleles,
      spw1-1 and spw1-2, show the same floral phenotype and did not affect vegetative
      development. We show that SPW1 is a rice APETALA3 homolog, OsMADS16. In contrast,
      two strong alleles of the dl locus, drooping leaf-superman1 (dl-sup1) and
      drooping leaf-superman2 (dl-sup2), cause the complete transformation of the
      gynoecium into stamens. In these strong mutants, many ectopic stamens are formed
      in the region where the gynoecium is produced in the wild-type flower and they
      are arranged in a non-whorled, alternate pattern. The intermediate allele dl-1
      (T65), results in an increase in the number of stamens and stigmas, and carpels
      occasionally show staminoid characteristics. In the weakest mutant, dl-2, most of
      the flowers are normal. All four dl alleles cause midrib-less drooping leaves.
      The flower of the double mutant, spw1 dl-sup, produces incompletely
      differentiated organs indefinitely after palea-like organs are produced in the
      position where lodicules are formed in the wild-type flower. These incompletely
      differentiated organs are neither stamens nor carpels, but have partial floral
      identity. Based on genetic and molecular results, we postulate a model of stamen
      and carpel specification in rice, with DL as a novel gene controlling carpel
      identity and acting mutually and antagonistically to the class B gene, SPW1.

PMID- 12506002
TI  - Drosophila MBF1 is a co-activator for Tracheae Defective and contributes to the
      formation of tracheal and nervous systems.
AB  - During gene activation, the effect of binding of transcription factors to cis
      acting DNA sequences is transmitted to RNA polymerase by means of co-activators.
      Although co-activators contribute to the efficiency of transcription, their
      developmental roles are poorly understood. We used Drosophila to conduct
      molecular and genetic dissection of an evolutionarily conserved but unique co
      activator, Multiprotein Bridging Factor 1 (MBF1), in a multicellular organism.
      Through immunoprecipitation, MBF1 was found to form a ternary complex including
      MBF1, TATA-binding protein (TBP) and the bZIP protein Tracheae Defective
      (TDF)/Apontic. We have isolated a Drosophila mutant that lacks the mbf1 gene in
      which no stable association between TBP and TDF is detectable, and transcription
      of a TDF-dependent reporter gene is reduced by 80%. Although the null mutants of
      mbf1 are viable, tdf becomes haploinsufficient in mbf1-deficient background,
      causing severe lesions in tracheae and the central nervous system, similar to
      those resulting from a complete loss of tdf function. These data demonstrate a
      crucial role of MBF1 in the development of tracheae and central nervous system.

PMID- 12506003
TI  - Requirements for transcriptional repression and activation by Engrailed in
      Drosophila embryos.
AB  - Genetic analysis shows that Engrailed (En), a homeodomain-containing
      transcription factor, has both negative and positive targets. Negative regulation
      is expected from a factor that has a well-defined repressor domain but activation
      is harder to comprehend. We used VP16En, a form of En that had its repressor
      domain replaced by the activation domain of VP16, to show that En activates
      targets using two parallel routes, by repressing a repressor and by being a bona
      fide activator. We identified the intermediate repressor activity as being
      encoded by sloppy paired 1 and 2 and showed that bona fide activation is
      dramatically enhanced by Wingless signaling. Thus, En is a bifunctional
      transcription factor and the recruitment of additional cofactors presumably
      specifies which function prevails on an individual promoter. Extradenticle (Exd)
      is a cofactor thought to be required for activation by Hox proteins. However, in
      thoracic segments, Exd is required for repression (as well as activation) by En.
      This is consistent with in vitro results showing that Exd is involved in
      recognition of positive and negative targets. Moreover, we provide genetic
      evidence that, in abdominal segments, Ubx and Abd-A, two homeotic proteins not
      previously thought to participate in the segmentation cascade, are also involved
      in the repression of target genes by En. We suggest that, like Exd, Ubx and Abd-A
      could help En recognize target genes or activate the expression of factors that
      do so.

PMID- 12506005
TI  - Three Brick genes have distinct functions in a common pathway promoting polarized
      cell division and cell morphogenesis in the maize leaf epidermis.
AB  - We have taken a genetic approach to investigating cytoskeleton-dependent
      mechanisms governing cell morphogenesis in the maize leaf epidermis. Previously,
      we showed that the Brick1 (Brk1) gene is required for the formation of epidermal
      cell lobes as well as for properly polarized divisions of stomatal subsidiary
      mother cells, and encodes an 8 kDa protein highly conserved in plants and
      animals. Here, we show that two additional Brick genes, Brk2 and Brk3, are
      involved in the same aspects of epidermal cell morphogenesis and division. As
      shown previously for Brk1, analysis of the cytoskeleton shows that Brk2 and Brk3
      are required for the formation of local F-actin enrichments associated with lobe
      outgrowth in wild-type cells. Analysis of brk1;brk2, brk1;brk3 and brk2;brk3
      double mutants shows that their phenotypes are the same as those of brk single
      mutants. Mosaic analysis shows that Brk1 acts non cell-autonomously over a short
      distance. By contrast, Brk2 and Brk3 act cell-autonomously to promote pavement
      cell lobe formation, but Brk3 acts non cell-autonomously, and Brk2 partially non
      cell-autonomously, to promote polarized subsidiary mother cell divisions.
      Together, these observations indicate that all three Brk genes act in a common
      pathway in which each Brk gene has a distinct function. Recent work demonstrating
      a function for the mammalian homolog of BRK1 (HSPC300) in activation of Arp2/3
      dependent actin polymerization implicates the Brk pathway in local regulation of
      actin polymerization in plant cells.

PMID- 12506004
TI  - Engrailed cooperates with extradenticle and homothorax to repress target genes in
      Drosophila.
AB  - Engrailed is a key transcriptional regulator in the nervous system and in the
      maintenance of developmental boundaries in Drosophila, and its vertebrate
      homologs regulate brain and limb development. Here, we show that the functions of
      both of the Hox cofactors Extradenticle and Homothorax play essential roles in
      repression by Engrailed. Mutations that remove either of them abrogate the
      ability of Engrailed to repress its target genes in embryos, both cofactors
      interact directly with Engrailed, and both stimulate repression by Engrailed in
      cultured cells. We suggest a model in which Engrailed, Extradenticle and
      Homothorax function as a complex to repress Engrailed target genes. These studies
      expand the functional requirements for extradenticle and homothorax beyond the
      Hox proteins to a larger family of non-Hox homeodomain proteins.

PMID- 12506006
TI  - The tumor-suppressor and cell adhesion molecule Fat controls planar polarity via
      physical interactions with Atrophin, a transcriptional co-repressor.
AB  - Fat is an atypical cadherin that controls both cell growth and planar polarity.
      Atrophin is a nuclear co-repressor that is also essential for planar polarity;
      however, it is not known what genes Atrophin controls in planar polarity, or how
      Atrophin activity is regulated during the establishment of planar polarity. We
      show that Atrophin binds to the cytoplasmic domain of Fat and that Atrophin
      mutants show strong genetic interactions with fat. We find that both Atrophin and
      fat clones in the eye have non-autonomous disruptions in planar polarity that are
      restricted to the polar border of clones and that there is rescue of planar
      polarity defects on the equatorial border of these clones. Both fat and Atrophin
      are required to control four-jointed expression. In addition our mosaic analysis
      demonstrates an enhanced requirement for Atrophin in the R3 photoreceptor. These
      data lead us to a model in which fat and Atrophin act twice in the determination
      of planar polarity in the eye: first in setting up positional information through
      the production of a planar polarity diffusible signal, and later in R3 fate
      determination.

PMID- 12506007
TI  - Invariant Sema5A inhibition serves an ensheathing function during optic nerve
      development.
AB  - Retinal axon pathfinding from the retina into the optic nerve involves the growth
      promoting axon guidance molecules L1, laminin and netrin 1, each of which governs
      axon behavior at specific regions along the retinal pathway. In identifying
      additional molecules regulating this process during embryonic mouse development,
      we found that transmembrane Semaphorin5A mRNA and protein was specifically
      expressed in neuroepithelial cells surrounding retinal axons at the optic disc
      and along the optic nerve. Given that growth cone responses to a specific
      guidance molecule can be altered by co-exposure to a second guidance cue, we
      examined whether retinal axon responses to Sema5A were modulated by other
      guidance signals axons encountered along the retinal pathway. In growth cone
      collapse, substratum choice and neurite outgrowth assays, Sema5A triggered an
      invariant inhibitory response in the context of L1, laminin, or netrin 1
      signaling, suggesting that Sema5A inhibited retinal axons throughout their course
      at the optic disc and nerve. Antibody-perturbation studies in living embryo
      preparations showed that blocking of Sema5A function led to retinal axons
      straying out of the optic nerve bundle, indicating that Sema5A normally helped
      ensheath the retinal pathway. Thus, development of some CNS nerves requires
      inhibitory sheaths to maintain integrity. Furthermore, this function is
      accomplished using molecules such as Sema5A that exhibit conserved inhibitory
      responses in the presence of co-impinging signals from multiple families of
      guidance molecules.

PMID- 12506008
TI  - Separable roles of UFO during floral development revealed by conditional
      restoration of gene function.
AB  - The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral
      development in Arabidopsis including specification of organ identity in the
      second and third whorls and the proper pattern of primordium initiation in the
      inner three whorls. UFO is expressed in a dynamic pattern during the early phases
      of flower development. Here we dissect the role of UFO by ubiquitously expressing
      it in ufo loss-of-function flowers at different developmental stages and for
      various durations using an ethanol-inducible expression system. The previously
      known functions of UFO could be separated and related to its expression at
      specific stages of development. We show that a 24- to 48-hour period of UFO
      expression from floral stage 2, before any floral organs are visible, is
      sufficient to restore normal petal and stamen development. The earliest
      requirement for UFO is during stage 2, when the endogenous UFO gene is
      transiently expressed in the centre of the wild-type flower and is required to
      specify the initiation patterns of petal, stamen and carpel primordia. Petal and
      stamen identity is determined during stages 2 or 3, when UFO is normally
      expressed in the presumptive second and third whorl. Although endogenous UFO
      expression is absent from the stamen whorl from stage 4 onwards, stamen identity
      can be restored by UFO activation up to stage 6. We also observed floral
      phenotypes not observed in loss-of-function or constitutive gain-of-function
      backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

PMID- 12506009
TI  - The Dictyostelium prestalk cell inducer DIF regulates nuclear accumulation of a
      STAT protein by controlling its rate of export from the nucleus.
AB  - Dd-STATc becomes tyrosine phosphorylated, dimerises and accumulates in the nuclei
      of Dictyostelium cells exposed to DIF, the chlorinated hexaphenone that directs
      prestalk cell differentiation. By performing cytoplasmic photobleaching of living
      cells, we show that DIF inhibits the nuclear export of Dd-STATc. Within Dd-STATc
      there is a 50 amino acid region containing several consensus CRM1 (exportin 1)
      dependent nuclear export signals (NESs). Deletion of this region causes Dd-STATc
      to accumulate in the nucleus constitutively and, when coupled to GFP, the same
      region directs nuclear export. We show that the N-terminal-proximal 46 amino
      acids are necessary for nuclear accumulation of Dd-STATc and sufficient to direct
      constitutive nuclear accumulation when fused to GFP. Combining the photobleaching
      and molecular analyses, we suggest that DIF-induced dimerisation of Dd-STATc
      functionally masks the NES-containing region and that this leads to nett nuclear
      accumulation, directed by the N-terminal-proximal import signals. These results
      show that the regulated nuclear accumulation of a STAT protein can be controlled
      at the level of nuclear export and they also provide a better understanding of
      the mechanism whereby DIF directs cell type divergence.

PMID- 12506010
TI  - The secreted Frizzled-related protein Sizzled functions as a negative feedback
      regulator of extreme ventral mesoderm.
AB  - The prevailing model of dorsal ventral patterning of the amphibian embryo
      predicts that the prospective mesoderm is regionalized at gastrulation in
      response to a gradient of signals. This gradient is established by diffusible BMP
      and Wnt inhibitors secreted dorsally in the Spemann organizer. An interesting
      question is whether ventrolateral tissue passively reads graded levels of
      ventralizing signals, or whether local self-organizing regulatory circuits may
      exist on the ventral side to control cell behavior and differentiation at a
      distance from the Organizer. We provide evidence that sizzled, a secreted
      Frizzled-related protein expressed ventrally during and after gastrulation,
      functions in a negative feedback loop that limits allocation of mesodermal cells
      to the extreme ventral fate, with direct consequences for morphogenesis and
      formation of the blood islands. Morpholino-mediated knockdown of Sizzled protein
      results in expansion of ventral posterior mesoderm and the ventral blood islands,
      indicating that this negative regulation is required for proper patterning of the
      ventral mesoderm. The biochemical activity of sizzled is apparently very
      different from that of other secreted Frizzled-related proteins, and does not
      involve inhibition of Wnt8. Our data are consistent with the existence of some
      limited self-organizing properties of the extreme ventral mesoderm.

PMID- 12506011
TI  - Critical role for PI 3-kinase in the control of erythropoietin-induced erythroid
      progenitor proliferation.
AB  - The production of red blood cells is tightly regulated by erythropoietin (Epo).
      The phosphoinositide 3-kinase (PI 3-kinase) pathway was previously shown to be
      activated in response to Epo. We studied the role of this pathway in the control
      of Epo-induced survival and proliferation of primary human erythroid progenitors.
      We show that phosphoinositide 3 (PI 3)-kinase associates with 4 tyrosine
      phosphorylated proteins in primary human erythroid progenitors, namely insulin
      receptor substrate-2 (IRS2), Src homology 2 domain-containing inositol 5'
      phosphatase (SHIP), Grb2-associated binder-1 (Gab1), and the Epo receptor (EpoR).
      Using different in vitro systems, we demonstrate that 3 alternative pathways
      independently lead to Epo-induced activation of PI 3-kinase and phosphorylation
      of its downstream effectors, Akt, FKHRL1, and P70S6 kinase: through direct
      association of PI 3-kinase with the last tyrosine residue (Tyr479) of the Epo
      receptor (EpoR), through recruitment and phosphorylation of Gab proteins via
      either Tyr343 or Tyr401 of the EpoR, or through phosphorylation of IRS2 adaptor
      protein. The mitogen-activated protein (MAP) kinase pathway was also activated by
      Epo in erythroid progenitors, but we found that this process is independent of PI
      3-kinase activation. In erythroid progenitors, the functional role of PI 3-kinase
      was both to prevent apoptosis and to stimulate cell proliferation in response to
      Epo stimulation. Finally, our results show that PI 3-kinase-mediated
      proliferation of erythroid progenitors in response to Epo occurs mainly through
      modulation of the E3 ligase SCF(SKP2), which, in turn, down-regulates p27(Kip1)
      cyclin-dependent kinase (CDK) inhibitor via proteasome degradation.

PMID- 12506012
TI  - Macrophage inflammatory protein 1-alpha (MIP-1 alpha ) triggers migration and
      signaling cascades mediating survival and proliferation in multiple myeloma (MM)
      cells.
AB  - Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha
      (MIP-1 alpha) is crucially involved in the development of osteolytic bone lesions
      in multiple myeloma (MM). The current study was designed to determine the direct
      effects of MIP-1 alpha on MM cells. Thus, we were able to demonstrate that MIP-1
      alpha acts as a potent growth, survival, and chemotactic factor in MM cells. MIP
      1 alpha-induced signaling involved activation of the AKT/protein kinase B (PKB)
      and the mitogen-activated protein kinase (MAPK) pathway. In addition, inhibition
      of AKT activation by phosphatidylinositol 3- kinase (PI3-K) inhibitors did not
      influence MAPK activation, suggesting that there is no cross talk between MIP-1
      alpha-dependent activation of the PI3-K/AKT and extracellular-regulated kinase
      (ERK) pathway. Our data suggest that besides its role in development of
      osteolytic bone destruction, MIP-1 alpha also directly affects cell signaling
      pathways mediating growth, survival, and migration in MM cells and provide
      evidence that MIP-1 alpha might play a pivotal role in the pathogenesis of MM.

PMID- 12506013
TI  - Opposing effects of PML and PML/RAR alpha on STAT3 activity.
AB  - Promyelocytic leukemia protein PML acts as a tumor suppressor, whereas its
      chimeric mutant promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR
      alpha) causes acute promyelocytic leukemia (APL). Because PML has been shown to
      form transcription-regulatory complexes with various molecules, we speculated
      that PML and/or PML/RAR alpha might affect signal transducer and activator of
      transcription 3 (STAT3) activity, which plays a crucial role in granulocyte
      colony-stimulating factor (G-CSF)-induced growth and survival of myeloid cells.
      In luciferase assays, PML inhibited STAT3 activity in NIH3T3, 293T, HepG2, and
      32D cells. PML formed a complex with STAT3 through B-box and COOH terminal
      regions in vitro and in vivo, thereby inhibiting its DNA binding activity.
      Although PML/RAR alpha did not interact with STAT3, it dissociated PML from STAT3
      and restored its activity suppressed by PML. To assess the biologic significance
      of these findings, we introduced PML and PML/RAR alpha into interleukin-3 (IL-3)
      dependent Ba/F3 cells expressing the chimeric receptor composed of extracellular
      domain of G-CSF-R and cytoplasmic domain of gp130, in which gp130-mediated growth
      is essentially dependent on STAT3 activity. Neither PML nor PML/RAR alpha
      affected IL-3-dependent growth of these clones. By contrast, gp130-mediated
      growth was abrogated by PML, whereas it was enhanced by PML/RAR alpha. These
      results reveal new functions of PML and PML/RAR alpha and suggest that
      dysregulated STAT3 activity by PML/RAR alpha may participate in the pathogenesis
      of APL.

PMID- 12506014
TI  - Elevated prothrombin results in clots with an altered fiber structure: a possible
      mechanism of the increased thrombotic risk.
AB  - Individuals with elevated prothrombin levels are at increased risk of venous
      thrombosis. To understand the mechanism behind this observation, we studied the
      effect of prothrombin concentration on thrombin generation and fibrin clot
      structure. The pattern of thrombin generation was directly related to the
      prothrombin level at all concentrations tested. From 0% to 300% of normal plasma
      levels of prothrombin, increasing the prothrombin concentration increased the
      initial rate, peak, and total amount of thrombin generated. Importantly, fibrin
      clot structure was also affected by the prothrombin concentration. Fibrin clots
      made from prothrombin concentrations less than 10% of plasma levels were weak and
      poorly formed. Fibrin clots made at 10% to 100% of plasma levels of prothrombin
      had similar fiber structures (mass-to-length ratio; mu). However, the fiber mass
      to-length ratio decreased with increasing prothrombin levels more than 100% of
      plasma levels, in a dose-dependent manner. These results suggest that increased
      levels of prothrombin alter thrombin generation and clot structure. Specifically,
      elevated prothrombin levels produce clots with reduced fibrin mass-to-length
      ratios compared with normal clots. We hypothesize that this alteration in fibrin
      clot structure is an important determinant of the risk of thrombosis.

PMID- 12506015
TI  - CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation.
AB  - CD28 is the quintessential costimulatory molecule expressed on CD4(+) and CD8(+)
      T cells. During chronic infections and the normal aging process, CD28 expression
      is lost, compromising the functional activity of T cells. CD28 loss is promoted
      by replicative stress, particularly in the presence of tumor necrosis factor
      alpha, owing to an inoperative CD28 initiator element. It is currently unknown
      whether CD28 loss is irreversible. The present study examined cytokines for their
      ability to reinduce CD28 expression. CD4(+)CD28(null) T cells constitutively
      expressed interleukin-12 (IL-12) alpha and beta receptors, which were functional
      and allowed for the up-regulation of the signal transducer and activator of
      transcription-4 (STAT-4)-dependent gene CD161. Costimulation of the T-cell and IL
      12 receptors induced the transcription of CD28 in approximately 50% of
      CD4(+)CD28(null) T-cell clones and lines. IL-12 by itself did not restore CD28
      expression. Up-regulation of CD28 after IL-12 exposure correlated with the
      reassembly of the CD28-initiator protein complex. The re-expressed CD28 was
      functional and restored the ability of CD4(+)CD28(null) T cells to express CD25
      and CD40 ligand. Our data suggest that IL-12 may, in part, functionally rescue
      senescent CD4(+) T cells.

PMID- 12506016
TI  - Hyperhomocysteinemia accelerates atherosclerosis in cystathionine beta-synthase
      and apolipoprotein E double knock-out mice with and without dietary perturbation.
AB  - Although hyperhomocysteinemia is an independent risk factor for cardiovascular
      disease, a direct role for homocysteine (Hcy) in this disease remains to be
      shown. Whereas diet-induced hyperhomocysteinemia promotes atherosclerosis in
      animal models, the effects of Hcy on atherogenesis in the absence of dietary
      perturbations is not known. We have generated double knock-out mice with targeted
      deletions of the genes for apolipoprotein E (apoE) and cystathionine beta
      synthase (CBS), which converts Hcy to cystathionine. ApoE(-/-)/CBS(-/-) mice
      developed aortic lesions even in the absence of dietary manipulation; lesion area
      and lesion cholesteryl ester (CE) and triglyceride (TG) contents increased with
      animal age and plasma Hcy levels. Plasma total cholesterol was significantly
      increased, whereas high density lipoprotein (HDL) cholesterol and TG
      concentrations of apoE(-/-)/CBS(-/-) mice were decreased. Cholesterol
      esterification and activities of enzymes catalyzing CE or TG formation in the
      vessel wall and in peritoneal macrophages were not changed by
      hyperhomocysteinemia. However, uptake of human acetyl-LDL, but not native low
      density lipoprotein (LDL), by mouse peritoneal macrophages was higher in the
      presence of hyperhomocysteinemia. These results suggest that isolated
      hyperhomocysteinemia is atherogenic and alters hepatic and macrophage lipoprotein
      metabolism, in part, by enhancing uptake of modified LDL.

PMID- 12506017
TI  - Induction of heme oxygenase-1 and stimulation of cGMP production by hemin in
      aortic tissues from hypertensive rats.
AB  - Heme oxygenase (HO) and carbon monoxide (CO) have been implicated in the
      modulation of various cardiovascular functions including blood pressure (BP)
      regulation. Up-regulating the HO/CO system lowers BP in young (8-week-old) but
      not in adult (20-week-old) spontaneously hypertensive rats (SHRs). The mechanisms
      for this selective effect are largely unknown. We investigated the effects of HO
      1 inducer, hemin, on the HO/CO-soluble gyanylyl cyclase (sGC)/cGMP system in the
      aorta of prehypertensive (4-week-old) young and adult SHRs as well as age-matched
      Wistar-Kyoto rats (WKYs). Reduced expressions of HO-1, HO-2, and sGC proteins
      associated with depressed HO activity and cGMP levels were detected in young
      SHRs. These deficiencies were significantly reversed by hemin treatment.
      Macrophage infiltration of vascular tissues was more significant in adult SHRs
      than adult WKYs, but invisible in young SHRs and WKYs. Hemin treatment did not
      alter macrophage infiltration of vascular tissues in young SHRs. The same hemin
      administration resulted in a significant decrease in BP (from 148.6 +/- 3.2 to
      125.8 +/- 2.6 mmHg, P <.01) in young SHRs, but not in prehypertensive or adult
      SHRs or WKYs of all ages. The HO inhibitor zinc protoporphyrin abrogated the
      hemin effect in young SHRs. Aortic tissues became desensitized to YC-1, an
      activator sGC, in adult SHRs. Thus, in young SHRs the expression and function of
      the HO/CO-sGC/cGMP system were suppressed, constituting a pathogenic mechanism
      for the development of hypertension. In adult SHRs, the HO/CO-sGC/cGMP system
      appeared normal, but desensitization of the sGC/cGMP pathway caused hypertension
      to prevail.

PMID- 12506018
TI  - Stimulation of osteoprotegerin production is responsible for osteosclerosis in
      mice overexpressing TPO.
AB  - Myelofibrosis and osteosclerosis are prominent features arising in mice
      overexpressing thrombopoietin (TPO). The pivotal role of transforming growth
      factor beta 1 (TGF-beta 1) in the pathogenesis of myelofibrosis has been
      documented, but the mechanisms mediating osteosclerosis remain unclear. Here, we
      used mice deficient in osteoprotegerin (OPG), a secreted inhibitor of bone
      resorption, to determine whether osteosclerosis occurs through a deregulation of
      osteoclastogenesis. Marrow cells from opg-deficient mice (opg(-/-)) or wild-type
      (WT) littermates were infected with a retrovirus encoding TPO and engrafted into
      an opg(-/-) or WT background for long-term reconstitution. The 4 combinations of
      graft/host (WT/WT, opg(-/-)/opg(-/-), opg(-/-)/WT, and WT/opg(-/-)) were studied.
      Elevation of TPO and TGF-beta 1 levels in plasma was similar in the 4
      experimental groups and all the mice developed a similar myeloproliferative
      syndrome associated with severe myelofibrosis. Osteosclerosis developed in WT
      hosts engrafted with WT or opg(-/-) hematopoietic cells and was associated with
      increased OPG levels in plasma and decreased osteoclastogenesis. In contrast,
      opg(-/-) hosts exhibited an osteoporotic phenotype and a growth of bone
      trabeculae was rarely seen. These findings suggest that osteosclerosis in mice
      with TPO overexpression occurs predominantly via an up-regulation of OPG in host
      stromal cells leading to disruption of osteoclastogenesis.

PMID- 12506019
TI  - The serine protease granzyme M is preferentially expressed in NK-cell, gamma
      delta T-cell, and intestinal T-cell lymphomas: evidence of origin from
      lymphocytes involved in innate immunity.
AB  - Granzyme M (GM) is a novel serine protease whose expression is highly restricted
      to natural killer (NK) cells, CD3(+)CD56(+) T cells, and gamma delta T cells.
      Using a GM-specific monoclonal antibody, we analyzed the expression of GM in 214
      mature T-cell and NK-cell lymphomas. GM was preferentially expressed in nasal
      NK/T-cell lymphomas (100%), gamma delta T-cell lymphomas (100%), and intestinal T
      cell lymphomas (85%). In contrast, GM expression was present at low prevalence in
      mycosis fungoides/Sezary syndrome (3%), anaplastic large-cell lymphoma (6%),
      panniculitis-like T-cell lymphoma (11%), and angioimmunoblastic T-cell lymphoma
      (0%) cases. Peripheral T-cell lymphomas of unspecified subtype showed an
      intermediate frequency (37%) of GM expression, consistent with their
      heterogeneous origin. We conclude that GM expression is a distinctive feature of
      the nasal NK/T-cell, gamma delta T-cell, and intestinal T-cell lymphomas, and
      suggest that these tumors develop from lymphocytes involved in innate immunity.

PMID- 12506020
TI  - Immunophenotypic evidence of leukemia after induction therapy predicts relapse:
      results from a prospective Children's Cancer Group study of 252 patients with
      acute myeloid leukemia.
AB  - Approximately 40% of children with acute myeloid leukemia (AML) who respond to
      initial therapy subsequently relapse. Multidimensional flow cytometry employing a
      standardized panel of monoclonal antibodies enables the detection of small
      numbers of occult leukemic cells that persist during therapy using technology
      adaptable by most clinical laboratories. We performed a prospective, blinded
      evaluation of bone marrow specimens obtained from 252 pediatric patients with de
      novo AML to determine whether detection of occult leukemia defined as more than
      or equal to 0.5% blasts with aberrant surface antigen expression as determined by
      flow cytometry was predictive of subsequent relapse. Occult leukemia was detected
      in 41 (16%) of the 252 patients who responded to initial induction therapy. In
      time-dependent multivariate analyses that controlled for allogeneic marrow
      transplantation, variable intervals between sample submission, age, sex, white
      blood cell count at diagnosis, presence of splenomegaly or hepatomegaly, and
      presence of more than 15% blasts in the marrow after the first course of
      induction, patients harboring occult leukemia were 4.8 times more likely to
      relapse (95% confidence interval [CI] = 2.8 to 8.4, P <.0001) and 3.1 times more
      likely to die (95% CI; 1.9 to 5.1, P <.0001) than those lacking leukemia
      detectable by flow cytometry. In this analysis, flow cytometric evidence of
      leukemia after the initiation of therapy emerged as the most powerful independent
      prognostic factor associated with poor outcome. Among patients in whom a marrow
      sample was available for analysis at the end of consolidation therapy, overall
      survival at 3 years was 41% versus 69% for patients with and without occult
      leukemia, respectively (P =.0058).

PMID- 12506021
TI  - Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP:
      an alternative to IVIG.
AB  - Intravenous immunoglobulin (IVIG) is used to treat immune thrombocytopenia
      resulting from a variety of autoimmune and nonautoimmune diseases such as
      idiopathic thrombocytopenic purpura (ITP), heparin-induced thrombocytopenia, and
      posttransfusion purpura. IVIG is a limited resource and although considered safe,
      may nevertheless carry some risk of transferring disease. Its high cost makes
      monoclonal antibodies, capable of mimicking the clinical effects of IVIG, highly
      desirable. We show here, using a murine model of ITP, that selected monoclonal
      antibodies can protect against thrombocytopenia. SCID mice were pretreated with 1
      of 21 monoclonal antibodies before induction of thrombocytopenia by antiplatelet
      antibody. Four antibodies reacted with the CD24 antigen on erythrocytes. Two
      antibodies were of the IgM class, and although one IgM antibody caused a minimal
      degree of anemia (P <.05), neither antibody ameliorated immune thrombocytopenia.
      One of 2 anti-CD24 antibodies of the IgG class ameliorated immune
      thrombocytopenia and blocked reticuloendothelial system function at the same
      doses that protected against thrombocytopenia. Some antibodies reactive with
      other circulating cell types also protected against immune-mediated
      thrombocytopenia while no antibody without a distinct target antigen in the mice
      was protective. Protective monoclonal antibodies significantly prevented
      thrombocytopenia at down to a 1000-fold lower dose (200 microg/kg) as compared
      with standard IVIG treatment (2 g/kg). It is concluded that monoclonal IgG with
      specificity for a circulating cellular target antigen may provide an alternative
      therapeutic approach to treating immune thrombocytopenia.

PMID- 12506022
TI  - Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders.
AB  - Imatinib mesylate (Gleevec), a small molecule inhibitor of abl, kit, and platelet
      derived growth factor receptor (PDGFR) tyrosine kinases, has been reported to be
      effective in the treatment of hypereosinophilic syndrome (HES) and a rare
      eosinophilia-associated chronic myeloid disorder (eos-CMD) characterized by the
      t(5;12)(q33;p13) cytogenetic abnormality. In the current study, we sought to
      confirm the preliminary observations in HES as well as evaluate the therapeutic
      value of imatinib in eos-CMD that is not associated with t(5;12)(q33;p13). Five
      patients with HES (all men, median age = 46 years) and 2 with eos-CMD (both men,
      aged 45 and 58 years) were treated with imatinib at a starting dose of 100 to 400
      mg/day. Cytogenetic studies showed no evidence of either the bcr-abl
      translocation or t(5;12)(q33;p13) in any patient. Screening of exons encoding the
      intracellular catalytic domains and extracellular ligand binding domains of PDGFR
      beta (exons 2-23) and c-kit (exons 1-21) in 6 patients demonstrated mostly
      previously known polymorphisms. At a median follow-up of 17 weeks (range, 10-33
      weeks), 2 patients with HES and 1 with eos-CMD have achieved complete clinical
      remission and 1 additional patient with HES has achieved a partial remission. In
      contrast to previous observations, all 4 responding patients had elevated serum
      interleukin-5 levels. Although the drug was well tolerated in most patients, a
      previously unrecognized treatment toxicity of acute left ventricular dysfunction
      occurred in a responding patient with HES within the first week of treatment.
      Myocardial biopsy revealed eosinophilic infiltration and degranulation, and the
      cardiogenic shock was reversed with the prompt institution of corticosteroid
      therapy.

PMID- 12506023
TI  - Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon
      alpha with an anti-CD20.
AB  - A controlled study has been carried out to assess the efficacy of rituximab, a
      chimeric antibody that binds to the B-cell surface antigen CD20, in 20 patients
      with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV)-positive chronic
      active liver disease, resistant to interferon alpha (IFN-alpha) therapy. They
      received an intravenous infusion of 375 mg/m(2) rituximab once a week for 4
      consecutive weeks. Infusion of rituximab had a good safety profile and no severe
      side effects were reported. Sixteen patients (80%) showed a complete response
      (CR), characterized by rapid improvement of clinical signs (disappearance of
      purpura and weakness arthralgia and improvement of peripheral neuropathy), and
      decline of cryocrit. CR was associated with a significant reduction of rheumatoid
      factor (RF) activity and anti-HCV antibody titers. Decline of IgG anti-HCV titers
      in the cryoprecipitates was usually associated with a favorable response (r =
      0.81; P <.005). No differences in the dynamics of B-cell depletion and recovery
      were found between responders and nonresponders. Molecular monitoring of the B
      cell response revealed disappearance/deletion of peripheral clones in the
      responders and great stability in the nonresponders. Rituximab had a deep impact
      on hepatitis C viremia; HCV RNA increased approximately twice the baseline levels
      in the responders, whereas it remained much the same in the nonresponders. Twelve
      (75%) of 16 responders remained in remission throughout the follow-up. The
      results indicate that rituximab has clinical and biologic activity in patients
      with HCV(+) MC. However, in view of the increased viremia in the responders,
      additional modes of application and combination of rituximab with other agents
      need to be investigated.

PMID- 12506024
TI  - Late relapses evolve from slow-responding subclones in t(12;21)-positive acute
      lymphoblastic leukemia: evidence for the persistence of a preleukemic clone.
AB  - TEL/AML1-positive childhood acute lymphoblastic leukemias (ALLs) generally have
      low-risk features, but still about 20% of patients relapse. Our initial molecular
      genetic analyses in 2 off-treatment relapses suggested that the initial and
      relapse clones represent different subclones that evolved from a common TEL/AML1
      positive, treatment-resistant precursor. In order to further elaborate on this
      hypothesis, we studied 2 patients with late systemic relapses of their TEL/AML1
      positive ALL (41 months and 49 months after initial diagnosis, respectively) who
      had distinct clonal antigen receptor gene rearrangements at diagnosis and
      relapse. These clone-specific markers enabled us to determine the responsiveness
      of the individual clones to treatment. The matching genomic TEL/AML1 breakpoints
      of the initial and the relapse clones in these patients confirmed their origin
      from a common progenitor cell. This proof was especially important in one of
      these 2 leukemias without a common antigen receptor gene rearrangement. Our
      retrospective analysis revealed that in both cases the relapse clone was already
      present at diagnosis. Despite their small sizes (5 x 10(-3) and 1 x 10(-4),
      respectively), we were able to detect their much slower responses to therapy
      compared with the dominant leukemic clone. Moreover, in all instances, these
      initially slow-responding clones, after they had developed into the relapse
      leukemia, were rapidly eradicated by the relapse treatment, underlining their
      different biology at the 2 time points of leukemia manifestation. We thus
      hypothesize that the minor clone was not fully malignant at initial diagnosis but
      acquired further mutations that may be necessary for the manifestation of
      relapse.

PMID- 12506025
TI  - The PML gene is not involved in the regulation of MHC class I expression in human
      cell lines.
AB  - The promyelocytic leukemia gene, PML, is a growth and transformation suppressor.
      An additional role for PML as a regulator of major histocompatibility complex
      (MHC) class I antigen presentation has been proposed in a murine model, which
      would account for evasion from host immunity of tumors bearing malfunctioning
      PML, such as acute promyelocytic leukemia. Here we investigated a possible role
      of PML for the control MHC class I expression in human cells. PML function was
      perturbed in human cell lines either by PML/RAR alpha transfection or by PML-
      specific RNA interference. Impairment of wild-type PML function was proved by a
      microspeckled disassembly of nuclear bodies (NBs), where the protein is normally
      localized, or by their complete disappearance. However, no MHC class I down
      regulation was observed in both instances. We next constructed a PML mutant, PML
      mut ex3, that is a human homolog of the murine PML mutant, truncated in exon 3,
      that was shown to down-regulate murine MHC class I. PML mut ex3 transfected in
      human cell lines exerted a dominant-negative effect since no PML molecules were
      detected in NBs but, instead, in perinuclear and cytoplasmic larger dot-like
      structures. Nevertheless, no down-regulation of MHC class I expression was
      evident. Moreover, neither transfection with PML mut ex3 nor PML-specific RNA
      interference affected the ability of gamma-interferon to up-regulate MHC class I
      expression. We conclude that, in human cell lines, PML is not involved directly
      in the regulation of MHC class I expression.

PMID- 12506026
TI  - Direct binding of Nur77/NAK-1 to the plasminogen activator inhibitor 1 (PAI-1)
      promoter regulates TNF alpha -induced PAI-1 expression.
AB  - Plasminogen activator inhibitor 1 (PAI-1) is the main fibrinolysis inhibitor, and
      high plasma levels are associated with an increased risk for vascular diseases.
      Inflammatory cytokines regulate PAI-1 through a hitherto unclear mechanism. Using
      reporter gene analysis, we could identify a region in the PAI-1 promoter that
      contributes to basal expression as well as to tumor necrosis factor alpha
      (TNFalpha) induction of PAI-1 in endothelial cells. Using this region as bait in
      a genetic screen, we could identify Nur77 (NAK-1, TR3, NR4A1) as an inducible DNA
      binding protein that binds specifically to the PAI-1 promoter. Nur77 drives
      transcription of PAI-1 through direct binding to an NGFI-B responsive element
      (NBRE), indicating monomeric binding and a ligand-independent mechanism. Nur77,
      itself, is transcriptionally up-regulated by TNFalpha. High expression levels of
      Nur77 and its colocalization with PAI-1 in atherosclerotic tissues indicate that
      the described mechanism for PAI-1 regulation may also be operative in vivo.

PMID- 12506027
TI  - Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle
      (SS) RBC adhesion.
AB  - The vasoocclusive crisis is the major clinical feature of sickle cell anemia,
      which is believed to be initiated or sustained by sickle (SS) red blood cell
      (RBC) adhesion to the vascular wall. SS RBCs, but not unaffected (AA) RBCs,
      adhere avidly to multiple components of the vascular wall, including laminin.
      Here we report a novel role for epinephrine and cyclic adenosine monophosphate
      (cAMP) in the regulation of human SS RBC adhesiveness via the laminin receptor,
      basal cell adhesion molecule/Lutheran (BCAM/Lu). Our data demonstrate that
      peripheral SS RBCs contain greater than 4-fold more cAMP than AA RBCs under basal
      conditions. Forskolin or the stress mediator epinephrine further elevates cAMP in
      SS RBCs and increases adhesion of SS RBCs to laminin in a protein kinase A (PKA)
      dependent manner, with the low-density population being the most responsive.
      Epinephrine-stimulated adhesion to laminin, mediated primarily via the beta 2
      adrenergic receptor, occurred in SS RBC samples from 46% of patients and was
      blocked by recombinant, soluble BCAM/Lu, implicating this receptor as a target of
      cAMP signaling. Thus, these studies demonstrate a novel, rapid regulation of SS
      RBC adhesion by a cAMP-dependent pathway and suggest that components of this
      pathway, particularly PKA, the beta 2-adrenergic receptor, and BCAM/Lu, should be
      further explored as potential therapeutic targets to inhibit SS RBC adhesion.

PMID- 12506028
TI  - Prevalence and clinical characteristics of myelodysplastic syndrome with bone
      marrow eosinophilia or basophilia.
AB  - By retrospectively analyzing 288 patients with de novo myelodysplastic syndrome
      (MDS), we sought to determine the prevalence and clinical characteristics of bone
      marrow eosinophilia and basophilia that were detected at presentation. Bone
      marrow eosinophilia and basophilia were defined as a differential count of each
      cell type exceeding 5.0% and 1.0%, respectively. Of 288 patients with MDS, 36
      (12.5%) fulfilled this criterion for bone marrow eosinophilia (MDS-Eos); 34
      patients (11.8%) showed basophilia (MDS-Bas), and 11 (3.8%) satisfied both
      criteria (MDS-EosBas). The remaining 229 patients had neither eosinophilia nor
      basophilia in their bone marrow (MDS(-/-)) at presentation. Cytogenetic analysis
      was carried out on unstimulated bone marrow cells obtained from 264 patients.
      When the cytogenetic categorization of the IPSS (International Prognostic Scoring
      System) for MDS was applied, significantly higher numbers of MDS-Eos and MDS-Bas
      patients had chromosomal abnormalities carrying intermediate or poor prognosis,
      compared with the MDS(-/-) patients. Specific chromosomal abnormalities and
      complex karyotypes were associated with MDS-Eos and/or MDS-Bas. In accordance
      with these results, the overall survival rate was significantly lower, and the
      evolution to acute myelogenous leukemia (AML) occurred more frequently in the MDS
      Eos and MDS-Bas than in the MDS(-/-) patients. Multivariate analysis demonstrated
      that bone marrow basophilia was an independent risk factor for evolution to AML.
      Our study indicates that bone marrow eosinophilia and basophilia in patients with
      MDS predict a poorer prognosis.

PMID- 12506029
TI  - Fetal liver stroma consists of cells in epithelial-to-mesenchymal transition.
AB  - Liver becomes the predominant site of hematopoiesis by 11.5 dpc (days after
      coitus) in the mouse and 15 gestational weeks in humans and stays so until the
      end of gestation. The reason the liver is the major hematopoietic site during
      fetal life is not clear. In this work, we tried to define which of the fetal
      liver microenvironmental cell populations would be associated with the
      development of hematopoiesis and found that a population of cells with mixed
      endodermal and mesodermal features corresponded to hematopoietic-supportive fetal
      liver stroma. Stromal cells generated from primary cultures or stromal lines from
      mouse or human fetal liver in the hematopoietic florid phase expressed both
      mesenchymal markers (vimentin, osteopontin, collagen I, alpha smooth muscle
      actin, thrombospondin-1, EDa fibronectin, calponin, Stro-1 antigens, myocyte
      enhancer factor 2C) and epithelial (alpha-fetoprotein, cytokeratins 8 and 18,
      albumin, E-cadherin, hepatocyte nuclear factor 3 alpha) markers. Such a cell
      population fits with the description of cells in epithelial-to-mesenchymal
      transition (EMT), often observed during development, including that of the liver.
      The hematopoietic supportive capacity of EMT cells was lost after hepatocytic
      maturation, induced by oncostatin M in the cell line AFT024. EMT cells were
      observed in the fetal liver microenvironment during the hematopoietic phase but
      not in nonhematopoietic liver by the end of gestation and in the adult. EMT cells
      represent a novel stromal cell type that may be generated from hepatic endodermal
      or mesenchymal stem cells or even from circulating hematopoietic stem cells
      (HSCs) seeding the liver rudiment.

PMID- 12506030
TI  - Factors affecting antibody levels after allogeneic hematopoietic cell
      transplantation.
AB  - To obtain insight into the mechanism(s) of posttransplantation humoral
      immunodeficiency, we evaluated factors affecting serum antibody levels against
      polio, tetanus, Haemophilus influenzae, and Streptococcus pneumoniae in 87
      patients. Patients with hematologic malignancies were randomized to receive
      marrow versus blood stem cells, which contain approximately 10 times more
      lymphocytes than marrow. Blood stem cell recipients did not have higher antibody
      levels than marrow recipients. Recipient pretransplantation antibody levels were
      correlated with the posttransplantation levels, especially in the first 6 months
      after transplantation when the correlation coefficients typically exceeded 0.6.
      Donor pretransplantation antibody levels had less of a correlation with
      posttransplantation levels in the recipient. Patient or donor age, total body
      irradiation, and graft-versus-host disease or its treatment appeared to have no
      effect. In conclusion, antibody levels in the first year after transplantation
      are affected primarily by pretransplantation antibody levels in the recipient
      and, to a lesser degree, in the donor. These findings suggest that immunization
      of the recipient and the donor before transplantation may be more effective in
      improving antibody immunity after transplantation than manipulating graft-versus
      host disease, changing conditioning, or increasing the number of lymphocytes in
      the graft.

PMID- 12506031
TI  - Central venous catheters and upper-extremity deep-vein thrombosis complicating
      immune heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a transient antibody-mediated
      hypercoagulability state strongly associated with lower-limb deep-vein thrombosis
      (DVT). Whether HIT is additionally associated with upper-limb DVT--either with or
      without central venous catheter (CVC) use--is unknown. We therefore studied 260
      patients with antibody-positive HIT to determine the influence of CVC use on
      frequency and localization of upper-extremity DVT in comparison with 2 non-HIT
      control populations (postoperative orthopedic surgery and intensive-care unit
      patients). Compared with the control populations, both upper- and lower-extremity
      DVTs were found to be associated with HIT. Upper-extremity DVTs occurred more
      frequently in HIT patients with a CVC (14 of 145 [9.7%]) versus none of 115 (0%)
      patients without a CVC (P =.000 35). All upper-extremity DVTs occurred at the CVC
      site (right, 12; left, 2; kappa = 1.0; P =.011). We conclude that a localizing
      vascular injury (CVC use) and a systemic hypercoagulability disorder (HIT)
      interact to explain upper-extremity DVT complicating HIT.

PMID- 12506032
TI  - A novel myeloid-like NK cell progenitor in human umbilical cord blood.
AB  - Natural killer (NK) cell differentiation from pluripotent CD34(+) human
      hematopoietic stem cells or oligopotent lymphoid progenitors has already been
      reported. In the present study, long-term cultures of the CD56(-)/CD34(-) myeloid
      like adherent cell fraction (ACF) from umbilical cord blood (UCB), characterized
      by the expression of CD14(+) as well as other myeloid markers, were set up with
      flt3 ligand (FL) and interleukin-15 (IL-15). The UCB/ACF gradually expressed the
      CD56 marker, which reached fairly high levels (approximately 90% of the cells
      were CD56(+)) by day 15. FL plus IL-15-driven ACF/CD56(+) cells progressively
      expressed a mature NK functional program lysing both NK- and lymphokine-activate
      killer (LAK)-sensitive tumor targets and producing high levels of interferon
      gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor, tumor
      necrosis factor alpha, and IL-10 upon stimulation with IL-12 and IL-18. Similar
      results were obtained when highly purified CD14(+) cells from UCB were cultured
      with FL and IL-15. In contrast, UCB/CD34(+) cells cultured under the same
      conditions showed a delayed expression of CD56 and behaved functionally
      differently in that they exhibited NK but not LAK cytotoxicity and produced
      significantly fewer cytokines. Kinetic studies on the phenotype of UCB/ACF or
      UCB/CD14(+) cells cultured in the presence of FL and IL-15 showed a rapid
      decrease in CD14 expression after day 5, which reached levels of zero by day 20.
      Approximately 60% of the CD56(+) derived from the UCB/ACF or the UCB/CD14(+)
      cells coexpressed CD14 by day 5. Taken together, our data support the role of
      CD14(+) myeloid-like cells within UCB as a novel progenitor for lymphoid NK
      cells.

PMID- 12506033
TI  - JunB gene expression is inactivated by methylation in chronic myeloid leukemia.
AB  - JunB is a component of the Jun family genes of the activating protein-1
      transcription factors that are important in the control of cell growth and
      differentiation and neoplastic transformation. Recently, it was demonstrated that
      transgenic mice specifically lacking JunB expression in the myeloid lineage
      developed a myeloproliferative disease, eventually progressing to blast crisis
      that resembled human chronic myeloid leukemia (CML). To gain further insights
      into the role of JunB in human CML, we examined peripheral blood from 17 healthy
      individuals and CML patients (11 in blastic crisis and 21 in chronic phase) by
      real-time quantitative reverse transcription-polymerase chain reaction analysis
      for the expression of JunB. The results showed the expression levels of JunB were
      significantly impaired in CML cases (blastic crisis < chronic phase < normal).
      Mutational analysis of the whole gene and methylation analysis of cytosine
      phosphate guanosine (CpG) sites at the promoter area were further performed to
      investigate the possible mechanisms. However, no mutation was found within the
      coding region or the 9 flanking evolutionarily conserved regions in all CML
      cases. Interestingly, in the promoter area of JunB gene, most of the CpG sites
      were methylated in CML cases; in contrast, none of these CpG sites were
      methylated in normal cases. Demethylation by treatment of hypermethylated K562
      cells with 5-aza-2'-deoxycytidine resulted in partial reactivation of JunB
      expression. Our results suggest that the down-regulated JunB expression in CML
      was due to the inactivation of JunB gene by methylation and the differential
      expression was correlated to the ratio of cells being methylated.

PMID- 12506035
TI  - Dendritic cells from CML patients have altered actin organization, reduced
      antigen processing, and impaired migration.
AB  - Chronic myeloid leukemia (CML) is characterized by expression of the BCR-ABL
      fusion gene that encodes a 210-kDa protein, which is a constitutively active
      tyrosine kinase. At least 70% of the oncoprotein is localized to the
      cytoskeleton, and several of the most prominent tyrosine kinase substrates for
      p210(BCR-ABL) are cytoskeletal proteins. Dendritic cells (DCs) are bone marrow
      derived antigen-presenting cells responsible for the initiation of immune
      responses. In CML patients, up to 98% of myeloid DCs generated from peripheral
      blood mononuclear cells are BCR-ABL positive. In this study we have compared the
      morphology and behavior of myeloid DCs derived from CML patients with control DCs
      from healthy individuals. We show that the actin cytoskeleton and shape of CML
      DCs of myeloid origin adherent to fibronectin differ significantly from those of
      normal DCs. CML-DCs are also defective in processing and presentation of
      exogenous antigens such as tetanus toxoid. The antigen-processing defect may be a
      consequence of the reduced capacity of CML-DCs to capture antigen via
      macropinocytosis or via mannose receptors when compared with DCs generated from
      healthy individuals. Furthermore, chemokine-induced migration of CML-DCs in vitro
      was significantly reduced. These observations cannot be explained by a difference
      in the maturation status of CML and normal DCs, because phenotypic analysis by
      flow cytometry showed a similar surface expression of maturation makers. Taken
      together, these results suggest that the defects in antigen processing and
      migration we have observed in CML-DCs may be related to underlying cytoskeletal
      changes induced by the p210(BCR-ABL) fusion protein.

PMID- 12506034
TI  - TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in
      Philadelphia chromosome-positive leukemia cells.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas
      ligand (FasL) have been implicated in antitumor immunity and therapy. In the
      present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)
      positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the
      possible contribution of these molecules to immunotherapy against Ph1-positive
      leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most
      of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1
      positive cell lines. The sensitivity to TRAIL was correlated with cell-surface
      expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell
      death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors.
      Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia
      patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5
      expression. Fas-associated death domain protein (FADD) and caspase-8, components
      of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas
      associating protein with death domain-like interleukin-1-converting
      enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were
      expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their
      differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell
      death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL
      specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma,
      Basel, Switzerland). These results suggested the potential utility of recombinant
      TRAIL as a novel therapeutic agent and the possible contribution of endogenously
      expressed TRAIL to immunotherapy against Ph1-positive leukemias.

PMID- 12506036
TI  - Promoter IV of the class II transactivator gene is essential for positive
      selection of CD4+ T cells.
AB  - Major histocompatibility complex class II (MHCII) expression is regulated by the
      transcriptional coactivator CIITA. Positive selection of CD4(+) T cells is
      abrogated in mice lacking one of the promoters (pIV) of the Mhc2ta gene. This is
      entirely due to the absence of MHCII expression in thymic epithelia, as
      demonstrated by bone marrow transfer experiments between wild-type and pIV(-/-)
      mice. Medullary thymic epithelial cells (mTECs) are also MHCII(-) in pIV(-/-)
      mice. Bone marrow-derived, professional antigen-presenting cells (APCs) retain
      normal MHCII expression in pIV(-/-) mice, including those believed to mediate
      negative selection in the thymic medulla. Endogenous retroviruses thus retain
      their ability to sustain negative selection of the residual CD4(+) thymocytes in
      pIV(-/-) mice. Interestingly, the passive acquisition of MHCII molecules by
      thymocytes is abrogated in pIV(-/-) mice. This identifies thymic epithelial cells
      as the source of this passive transfer. In peripheral lymphoid organs, the CD4(+)
      T-cell population of pIV(-/-) mice is quantitatively and qualitatively comparable
      to that of MHCII-deficient mice. It comprises a high proportion of CD1-restricted
      natural killer T cells, which results in a bias of the V beta repertoire of the
      residual CD4(+) T-cell population. We have also addressed the identity of the
      signal that sustains pIV expression in cortical epithelia. We found that the
      Jak/STAT pathways activated by the common gamma chain (CD132) or common beta
      chain (CDw131) cytokine receptors are not required for MHCII expression in thymic
      cortical epithelia.

PMID- 12506037
TI  - Bone marrow mesenchymal stem cells inhibit the response of naive and memory
      antigen-specific T cells to their cognate peptide.
AB  - Mesenchymal stem cells (MSCs) have been recently shown to inhibit T-cell
      proliferation to polyclonal stimuli. We characterized the effect of MSCs of bone
      marrow origin on the T-cell response of naive and memory T cells to their cognate
      antigenic epitopes. The immune response to murine male transplantation antigens,
      HY, was selected because the peptide identity and major histocompatibility
      complex (MHC) restriction of the immunodominant epitopes are known. C57BL/6
      female mice immunized with male cells were the source of memory T cells, whereas
      C6 mice transgenic for HY-specific T-cell receptor provided naive T cells.
      Responder cells were stimulated in vitro with male spleen cells or HY peptides in
      the presence or absence of MSCs. MSCs inhibited HY-specific naive and memory T
      cells in a dose-dependent fashion and affected cell proliferation, cytotoxicity,
      and the number of interferon gamma (IFN-gamma)-producing HY peptide-specific T
      cells. However, the MSC inhibitory effect did not selectively target antigen
      reactive T cells. When MSCs were added to the T-cell cultures in a Transwell
      system or MSCs were replaced by MSC culture supernatant, the inhibitory activity
      was abrogated. T-cell reactivity was also restored if MSCs were removed from the
      cultures. The expression of MHC molecules and the presence in culture of antigen
      presenting cells (APCs) or of CD4(+)/CD25(+) regulatory T cells were not required
      for MSCs to inhibit. We conclude that MSCs inhibit naive and memory T-cell
      responses to their cognate antigens. Overall our data suggest that MSCs
      physically hinder T cells from the contact with APCs in a noncognate fashion.

PMID- 12506038
TI  - A naturally occurring Tyr143His alpha IIb mutation abolishes alpha IIb beta 3
      function for soluble ligands but retains its ability for mediating cell adhesion
      and clot retraction: comparison with other mutations causing ligand-binding
      defects.
AB  - The molecular basis for the interaction between a prototypic non-I-domain
      integrin, alpha(IIb)beta(3), and its ligands remains to be determined. In this
      study, we have characterized a novel missense mutation (Tyr143His) in alpha(IIb)
      associated with a variant of Glanzmann thrombasthenia. Osaka-12 platelets
      expressed a substantial amount of alpha(IIb)beta(3) (36%-41% of control) but
      failed to bind soluble ligands, including a high-affinity alpha(IIb)beta(3)
      specific peptidomimetic antagonist. Sequence analysis revealed that Osaka-12 is a
      compound heterozygote for a single (521)T>C substitution leading to a Tyr143His
      substitution in alpha(IIb) and for the null expression of alpha(IIb) mRNA from
      the maternal allele. Given that Tyr143 is located in the W3 4-1 loop of the beta
      propeller domain of alpha(IIb), we examined the effects of Tyr143His or Tyr143Ala
      substitution on the expression and function of alpha(IIb)beta(3) and compared
      them with KO (Arg-Thr insertion between 160 and 161 residues of alpha(IIb)) and
      with the Asp163Ala mutation located in the same loop by using 293 cells. Each of
      them abolished the binding function of alpha(IIb)beta(3) for soluble ligands
      without disturbing alpha(IIb)beta(3) expression. Because immobilized fibrinogen
      and fibrin are higher affinity/avidity ligands for alpha(IIb)beta(3), we
      performed cell adhesion and clot retraction assays. In sharp contrast to KO
      mutation and Asp163Ala alpha(IIb)beta(3), Tyr143His alpha(IIb)beta(3)-expressing
      cells still had some ability for cell adhesion and clot retraction. Thus, the
      functional defect induced by Tyr143His alpha(IIb) is likely caused by its
      allosteric effect rather than by a defect in the ligand-binding site itself.
      These detailed structure-function analyses provide better understanding of the
      ligand-binding sites in integrins.

PMID- 12506039
TI  - Regulation of the cell-surface expression of an HTLV-I binding protein in human T
      cells during immune activation.
AB  - Little is known about the requirements for human T-cell leukemia virus type I
      (HTLV-I) entry, including the identity of the cellular receptor(s). Recently, we
      have generated an HTLV-I surface glycoprotein (SU) immunoadhesin, HTSU-IgG, which
      binds specifically to cell-surface protein(s) critical for HTLV-I-mediated entry
      in cell lines. Here, expression of the HTLV-I SU binding protein on primary cells
      of the immune system was examined. The immunoadhesin specifically bound to adult
      T cells, B cells, NK cells, and macrophages. Cell stimulation dramatically
      increased the amount of binding, with the highest levels of binding on CD4(+) and
      CD8(+) T cells. Naive (CD45RA(high), CD62L(high)) CD4(+) T cells derived from
      cord blood cells, in contrast to other primary cells and all cell lines examined,
      bound no detectable HTLV-I SU. However, following stimulation, the level of HTSU
      IgG binding was rapidly induced (fewer than 6 hours), reaching the level of
      binding seen on adult CD4(+) T cells by 72 hours. In contrast to HTLV-I virions,
      the soluble HTSU-IgG did not effect T-cell activation or proliferation. When
      incubated with human peripheral blood mononuclear cells in a mixed leukocyte
      reaction, HTSU-IgG inhibited proliferation at less than 1 ng/mL. These results
      indicate that cell-surface expression of the HTLV SU binding protein is up
      regulated during in vitro activation and suggest a role for the HTLV-I SU binding
      proteins in the immunobiology of CD4(+) T cells.

PMID- 12506040
TI  - Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize
      them to therapeutics by blocking adaptive cholesterol responses.
AB  - The mevalonate pathway produces many critical substances in cells, including
      sterols essential for membrane structure and isoprenoids vital to the function of
      many membrane proteins. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      is a rate-limiting enzyme in the mevalonate pathway. Because cholesterol is a
      product of this pathway, HMG-CoA reductase inhibitors (statins) are used to treat
      hypercholesterolemia. Statins are also toxic to several malignancies, including
      acute myeloid leukemia (AML). Although this toxicity has been attributed to the
      inhibition of Ras/Rho isoprenylation, we have previously shown that statin
      toxicity in primary AML cells (AMLs) does not correlate with Ras isoprenylation
      or with activating Ras mutations. In other studies, we have shown that hypoxic
      and oxidant injuries induce cholesterol increments in renal tubule cells and that
      statins sensitize these cells to injury by blocking protective cholesterol
      responses. We now demonstrate that exposing particular AMLs to radiochemotherapy
      induces much greater cellular cholesterol increments than those seen in similarly
      treated normal bone marrow. Treatment of these AMLs with mevastatin or zaragozic
      acid (which inhibits cholesterol synthesis but not isoprenoid synthesis)
      attenuates the cholesterol increments and sensitizes cells to radiochemotherapy.
      The extent of toxicity is affected by the availability of extracellular
      lipoproteins, further suggesting that cellular cholesterol is critical to cell
      survival in particular AMLs. Because zaragozic acid does not inhibit isoprenoid
      synthesis, these data suggest that cholesterol modulation is an important
      mechanism whereby statins exert toxic effects on some AMLs and that cholesterol
      modulators may improve therapeutic ratios in AML by impacting cholesterol
      dependent cytoresistance.

PMID- 12506041
TI  - Transactivation of the fucosyltransferase VII gene by human T-cell leukemia virus
      type 1 Tax through a variant cAMP-responsive element.
AB  - Human T-cell leukemic virus type 1 (HTLV-1)-infected T cells express the
      fucosyltransferase (Fuc-T) VII gene involved in the biosynthesis of the leukocyte
      sialyl Lewis X, which may be related to tissue infiltration in patients with
      malignant adult T-cell leukemia. HTLV-1 induces Fuc-T VII transcription through
      the viral transactivator Tax, although the underlying molecular mechanism remains
      unknown. In the present study, we analyzed the role of the cis-activating element
      in Tax activation using reporter constructs bearing the 5'-regulatory region of
      Fuc-T VII in Jurkat T cells. A sequence (GGCTGTGGGGGCGTCATATTGCCCTGG) covering a
      half-palindromic cyclic adenosine monophosphate (cAMP)-responsive element (CRE)
      was found to be required for Tax activation of the Fuc-T VII promoter. We further
      demonstrated that transcription factors of the CRE-binding protein
      (CREB)/activating transcription factor (ATF) family bind to this CRE-like
      sequence and that Tax binds in association with CREB and the coactivator CREB
      binding protein (CBP) in Jurkat T cells. This element, containing the G+C-rich
      flanking sequences, is homologous to the Tax-responsive viral CREs in the HTLV-1
      long terminal repeat (LTR)-promoter. Furthermore, CREM alpha, an isoform of CREB
      deficient in the glutamine-rich domains, was found to activate the Fuc-T VII
      promoter in a phosphorylation-independent manner, similar to the viral CRE in
      HTLV-1 LTR but in contrast to the phosphorylation-dependent activation of the
      cellular CREs by Tax. These findings indicate that the Fuc-T VII promoter is
      transactivated by Tax in concert with CBP through a CRE-like sequence in a manner
      similar to that of viral CRE in HTLV-1 LTR.

PMID- 12506042
TI  - Energy cost and muscular activity required for propulsion during walking.
AB  - We reasoned that with an optimal aiding horizontal force, the reduction in
      metabolic rate would reflect the cost of generating propulsive forces during
      normal walking. Furthermore, the reductions in ankle extensor electromyographic
      (EMG) activity would indicate the propulsive muscle actions. We applied
      horizontal forces at the waist, ranging from 15% body weight aiding to 15% body
      weight impeding, while subjects walked at 1.25 m/s. With an aiding horizontal
      force of 10% body weight, 1) the net metabolic cost of walking decreased to a
      minimum of 53% of normal walking, 2) the mean EMG of the medial gastrocnemius
      (MG) during the propulsive phase decreased to 59% of the normal walking
      magnitude, and yet 3) the mean EMG of the soleus (Sol) did not decrease
      significantly. Our data indicate that generating horizontal propulsive forces
      constitutes nearly half of the metabolic cost of normal walking. Additionally, it
      appears that the MG plays an important role in forward propulsion, whereas the
      Sol does not.

PMID- 12506043
TI  - Reperfusion injury is reduced in skeletal muscle by inhibition of inducible
      nitric oxide synthase.
AB  - This study evaluated the effects of the selective inducible nitric oxide synthase
      (iNOS) inhibitor N-[3-(aminomethyl)benzyl]acetamidine (1400W) on the
      microcirculation in reperfused skeletal muscle. The cremaster muscles from 32
      rats underwent 5 h of ischemia followed by 90 min of reperfusion. Rats received
      either 3 mg/kg 1400W or PBS subcutaneously before reperfusion. We found that
      blood flow in reperfused muscles was <45% of baseline in controls but sharply
      recovered to near baseline levels in 1400W-treated animals. There was a
      significant (P < 0.01 to P < 0.001) difference between the two groups at each
      time point throughout the 90 min of reperfusion. Vessel diameters remained <80%
      of baseline in controls during reperfusion, but recovered to the baseline level
      in the 1400W group by 20 min, and reached a maximum of 121 +/- 14% (mean +/- SD)
      of baseline in 10- to 20-micro m arterioles, 121 +/- 6% in 21- to 40-micro m
      arterioles, and 115 +/- 8% in 41- to 70-micro m arteries (P < 0.01 to P < 0.001).
      The muscle weight ratio between ischemia-reperfused (left) and non-ischemia
      reperfused (right) cremaster muscles was 193 +/- 42% of normal in controls and
      124 +/- 12% in the 1400W group (P < 0.001). Histology showed that neutrophil
      extravasation and edema were markedly reduced in 1400W-treated muscles compared
      with controls. We conclude that ischemia-reperfusion leads to increased
      generation of NO from iNOS in skeletal muscle and that the selective iNOS
      inhibitor 1400W reduces the negative effects of ischemia-reperfusion on vessel
      diameter and muscle blood flow. Thus 1400W may have therapeutic potential in
      treatment of ischemia-reperfusion injury.

PMID- 12506044
TI  - Temporal coordination of pharyngeal and laryngeal dynamics with breathing during
      swallowing: single liquid swallows.
AB  - The critical integration of timing and patterning between respiratory and
      swallowing events was studied with simultaneous videofluoroscopic and respiratory
      recording during single liquid swallows. Respiratory phase patterns and the
      onsets and durations of 12 predetermined swallowing events and associated
      respiratory activities were studied. Results showed four highly repeatable,
      temporally oriented sequences (clusters) of swallowing and related respiratory
      events. Two respiratory phase patterns were identified without statistically
      significant differences in frequency of occurrence between age, gender, or race.
      These findings will aid in the identification of normal and abnormal patterns of
      breathing and swallowing in patients with dysphagia.

PMID- 12506045
TI  - Regulation of brain water during acute hyperosmolality in ovine fetuses, lambs,
      and adults.
AB  - In adult rats, when plasma osmolality increases, water flows across the blood
      brain barrier down its concentration gradient from brain to plasma, and brain
      volume deceases. The brain responds to this stress by gaining osmotically active
      solutes, which limit water loss. This phenomenon is termed brain volume (water)
      regulation. We tested the hypothesis that brain volume regulation is more
      effective in young lambs and adult sheep than in fetuses, premature lambs, and
      newborn lambs. Brain water responses to acute hyperosmolality were measured in
      the cerebral cortex, cerebellum, and medulla of fetuses at 60 and 90% of
      gestation, premature ventilated lambs at 90% of gestation, newborn lambs, young
      lambs at 20-30 days of age, and adult sheep. After exposure of the sheep to
      increases in systemic osmolality with mannitol plus NaCl, brain water content and
      electrolytes were quantified. The ideal osmometer is a system in which
      impermeable solutes do not enter or leave in response to an osmotic stress. There
      were significant differences from an ideal osmometer in the cerebral cortex of
      fetuses at 90% of gestation, cerebral cortex, and cerebellum of newborn lambs,
      and cerebral cortex, cerebellum, and medulla of young lambs and adult sheep;
      however, there were no differences in the brain regions of fetuses at 60% of
      gestation and premature lambs, cerebellum and medulla of fetuses at 90% of
      gestation, and medulla of newborn lambs. We conclude that 1) brain water loss is
      maximal and brain volume regulation impaired in most brain regions of fetuses at
      60 and 90% of gestation and premature lambs; 2) brain volume regulation develops
      first in the cerebral cortex of the fetuses at 90% of gestation and in the
      cerebral cortex and cerebellum of newborn lambs, and then it develops in the
      medulla of the lambs at 20-30 days of age; 3) brain water loss is limited and
      volume regulation present in the brain regions of young lambs and adult sheep;
      and 4) the ability of the brain to exhibit volume regulation develops in a region
      and age-related fashion.

PMID- 12506046
TI  - Genetic models in applied physiology: selected contribution: effects of
      spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines,
      erythrocytes, and platelets.
AB  - This portion of the study quantified the effects of a 12-day space shuttle
      mission (Space Transport System-108/UF-1) on body and lymphoid organ masses,
      activation marker expression, cytokine secretion, and erythrocyte and thrombocyte
      characteristics in C57BL/6 mice. Animals in flight (Flt group) had 10-12% lower
      body mass compared with ground controls housed either in animal enclosure modules
      or under standard vivarium conditions (P < 0.001) and the smallest thymus and
      spleen masses. Percentages of CD25(+) lymphocytes, CD3(+)/CD25(+) T cells, and
      NK1.1(+)/CD25(+) natural killer cells from Flt mice were higher compared with
      both controls (P < 0.05). In contrast, CD71 expression was depressed in the Flt
      and animal enclosure module control mice compared with vivarium control animals
      (P < 0.001). Secretion of interferon-gamma, IL-2, and IL-4, but not tumor
      necrosis factor-alpha and IL-5, by splenocytes from Flt mice was decreased
      relative to either one or both ground controls (P < 0.05). Flt mice also had high
      red blood cell and thrombocyte counts compared with both sets of controls; low
      red blood cell volume and distribution width, percentage of reticulocytes, and
      platelet volume were also noted (P < 0.05) and were consistent with dehydration.
      These data indicate that relatively short exposure to the spaceflight environment
      can induce profound changes that may become significant during long-term space
      missions.

PMID- 12506048
TI  - Varicosities of intraretinal ganglion cell axons in human and nonhuman primates.
AB  - PURPOSE: To describe varicosities of intraretinal ganglion cell axons in the
      nerve fiber layer of human and nonhuman primate retinas. METHODS: Intraretinal
      ganglion cell axons of seven human donors (1-85 years old) and two nonhuman
      primates (Macaca mulatta, 15 and 17 years old) were immunohistochemically stained
      with an antibody of neurofilament on flatmounted retinas and examined with light
      microscopy. In addition, the axons within the retinal nerve fiber layer were
      examined with transmission electron microscopy in one human and one nonhuman
      retina. The variations of diameters of single axons were measured on transverse-
      and parallel-cut sections, and the frequency distributions of the diameters were
      statistically evaluated. RESULTS: Varicosities of the intraretinal ganglion cell
      axons were found throughout the retinas in both nonhuman primate and human eyes
      of all ages examined. The varicosities were rich in mitochondria and had
      desmosome- and hemidesmosome-like junctions with other axons and retinal glial
      cells. Measured on parallel-cut axons, the mean diameter (+/-SD) of varicosities
      was 2.7 +/- 0.9 micro m, whereas the mean diameter of intervaricosity regions was
      0.7 +/- 0.3 micro m. The diameter distribution for transverse-cut axons was also
      bimodal, but the two peaks were much closer because the peak of the larger
      diameter group decreased. CONCLUSIONS: The results demonstrated that intraretinal
      ganglion cell axons are predominantly varicose fibers in both human and nonhuman
      primates. Size variations exist within a single axon's diameter and thereby
      affect the patterns of diameter distribution seen in transverse-cut preparations.
      The mitochondria-rich varicosities and the presence of intercellular junctions
      suggest that the varicosities may be functional sites that serve local high
      energy demands of unmyelinated fibers and signal transmission.

PMID- 12506049
TI  - Impact of the environment on the mammalian corneal epithelium.
AB  - PURPOSE: To evaluate whether the content of ascorbic acid in the corneal
      epithelium and aqueous humor reflects seasonal fluctuations in parallel with
      environmental changes. METHODS: Reindeer, cattle, rabbits, and humans were
      examined, to cover a broad spectrum of overlapping habitats. Ascorbic acid was
      determined by high-performance liquid chromatography. The thickness of the
      corneal epithelium was measured, and the number of cells was counted in the
      tissue sections. RESULTS: Three groups of reindeer eyes were used, two of them
      collected during summer, the third group during winter. Ascorbate content did not
      show seasonal variation in either the corneal epithelium or the aqueous humor,
      whereas epithelial thickness and number of cells decreased significantly from
      summer to winter. In cattle, ascorbate content, thickness of the epithelium, and
      number of cells were lower in animals tended indoors compared with those tended
      outdoors, whereas ascorbate level in the aqueous humor remained similar in both
      cases. The rabbit showed significantly reduced ascorbate content in the corneal
      epithelium but not in the aqueous humor in tarsorrhaphy-treated eyes. This
      procedure did not change epithelial thickness, but the number of cells was
      slightly increased. The mean epithelial thickness in human corneas successively
      decreased with increasing latitude and decreasing radiation exposure from the
      summer season in Oslo to the midnight sun, polar night, conditions in Tromso, 10
      degrees far north, although the differences did not reach statistical
      significance. CONCLUSIONS: Ambient radiation is needed to sustain high ascorbic
      acid concentration in the corneal epithelium. Corneal epithelial thickness and
      number of cells are prone to seasonal fluctuations regulated by ambient
      radiation. In contrast, ascorbate content of the aqueous humor is uninfluenced by
      environmental change. It is suggested that seasonal adaptation of mammalian
      corneal epithelium in response to variation in ambient radiation may be nature's
      strategy for countering radiation damage to the eye.

PMID- 12506050
TI  - Configuration of the optic chiasm in humans with albinism as revealed by magnetic
      resonance imaging.
AB  - PURPOSE: To determine whether the size and configuration of the optic chiasm in
      humans with albinism is different from that in normal control subjects. METHODS:
      Seventeen patients and 15 control subjects underwent magnetic resonance imaging
      of the entire head. Images were reformatted to the chiasm region and analyzed
      with observer-independent morphometry and measurements by a blinded observer.
      RESULTS: The albino group showed significantly smaller chiasmatic widths, smaller
      optic nerves and tracts, and wider angles between nerves and tracts. Statistical
      morphometry showed a different configuration of the optic chiasm. CONCLUSIONS:
      Size and configuration of the optic chiasm in humans with albinism are distinctly
      different from those in normal control subjects and reflect the atypical crossing
      of optic fibers.

PMID- 12506051
TI  - Pathogenic role of retinal microglia in experimental uveoretinitis.
AB  - PURPOSE: To devise methods for unequivocal identification of activated retinal
      microglia in experimental autoimmune uveoretinitis (EAU) and to investigate their
      role in the development of EAU. METHODS: A group of Lewis rats underwent optic
      nerve axotomy with the application of N-4-(4-didecylaminostyryl)-N
      methylpyridinium iodide (4Di-10ASP) at the axotomy site. On days 3, 14, and 38
      after axotomy, the rats were killed, the eyes were enucleated, and the retinas
      were stained for OX42. Another group of such axotomized rats were immunized with
      S-antigen peptide and were killed on days 7 through 12 after the injection with
      peptide. The enucleated eyes were stained for OX42 and examined by confocal
      microscope. After axotomy, bone marrow (Y-->X) chimeric rats were injected with S
      antigen peptide and were killed on days 10 and 12 after injection. The retinas
      were evaluated by PCR with Y-specific primers. Finally, a group of axotomized
      rats was injected with the S-antigen peptide and killed on days 6, 8, 9, and 10
      after injection. Their enucleated eyes were examined for microglial expression of
      TNFalpha and for generation of peroxynitrite. RESULTS: In the axotomized, non-EAU
      eyes, 4Di-10ASP-labeled ganglion cells were detectable on days 3 and 14, and 4Di
      10ASP-containing OX42-positive cells (microglia) were found in the nerve fiber
      and other inner retinal layers on days 14 and 38. The S-antigen peptide-injected
      rats showed migration of the microglia (4Di-10ASP-positive and OX42-positive) to
      the photoreceptor cell layer on day 9, and these cells increased in number at
      this site on day 10. No macrophages (OX42-positive and 4Di-10ASP-negative) were
      present at this early stage of EAU, but such cells appeared in the retina on days
      11 and 12. PCR of the chimeric EAU retinas showed an absence of the Y chromosome
      amplified product on day 10, but the presence of this product was detected on day
      12. The expression of TNFalpha and generation of peroxynitrite were noted in the
      migrated microglia at the photoreceptor cell layer on days 9 and 10 of EAU.
      CONCLUSIONS: In the early phase of EAU, the microglia migrate to the
      photoreceptor cell layer where they generate TNFalpha and peroxynitrite. Such
      microglial migration and activation take place before infiltration of the
      macrophages. These findings indicate a novel pathogenic mechanism of EAU, in
      which retinal microglia may initiate retinitis with subsequent recruitment of
      circulation-derived phagocytes, leading to the amplification of uveoretinitis.

PMID- 12506052
TI  - Refractive changes induced by form deprivation in the mouse eye.
AB  - PURPOSE: Form-deprivation myopia has been induced in many different animal
      species. Underlying mechanisms are not well understood to date. In the current
      study the possibility of inducing refractive errors by form deprivation in the
      mouse (C57 BL/6) was investigated. METHODS: Thirty animals underwent a 13- to 20
      day monocular form-deprivation period by suture of the left eyelid before or
      after natural eye opening. A subsequent survival period was allowed in a group of
      animals. Retinoscopic refraction was performed at lid reopening and after the
      subsequent survival period, when applicable. Animals were killed and the eyes
      enucleated. The axial length of the eyes was measured in histochemically
      processed horizontal eye sections. A group of 30 age-matched normal control mice
      was also studied. RESULTS: Deprived eyes showed significant development of myopia
      compared with the contralateral fellow eye after transitory hypermetropia,
      regardless of whether they were deprived before or after natural eye opening. The
      refractive difference between form-deprived and corresponding fellow eyes was
      significantly correlated with the difference in axial length, which indicates
      that myopia is mainly axial. The differences exceeded those between eyes of age
      matched normal control mice. CONCLUSIONS: Form-deprivation myopia can be induced
      in the mouse. This model may be useful to investigate underlying mechanisms of
      myopia in mammals, because of easier handling and availability of genetically
      manipulated strains.

PMID- 12506053
TI  - Localization and activity of membrane dipeptidase in bovine ciliary epithelium.
AB  - PURPOSE: To investigate the localization and the activity of membrane dipeptidase
      (MDP) in the bovine eye. METHODS: A monoclonal antibody (mAb), 49C mAb, raised
      against bovine ciliary process was used to examine the localization of MDP.
      Conversion of leukotriene (LT)D4 to LTE4 was evaluated by enzyme-linked
      immunosorbent assay for LTE4. Hydrolytic activity (beta-lactamase activity) was
      evaluated with a fluorometric assay. To clarify the contribution of MDP to
      conversion of LTD4 and beta-lactamase activity, we separated MDP from other
      enzymes by 49C mAb-conjugated gel. RESULTS: The antigenic molecule of 49C mAb was
      shown to be MDP by amino acid sequencing. MDP was immunohistochemically detected
      in the ciliary pigmented and nonpigmented epithelial cells. Conversion of LTD4 to
      LTE4 in the ciliary process was much greater than that of the neural retina (NR).
      beta-Lactamase activity in the ciliary process was apparent, but that in the NR
      or the retinal pigment epithelium was negligible. Approximately 100% of beta
      lactamase activity in the ciliary process was catalyzed by the 49C mAb-bound
      fraction. Conversion of LTD4 was catalyzed by the 49C mAb-bound fraction (55% of
      total activity) and by the unbound fraction (45% of total activity). CONCLUSIONS:
      This study produced the first evidence of the presence of MDP in ciliary
      epithelial cells. The ciliary epithelium converts LTD4 to LTE4 and shows beta
      lactamase activity. Conversion of LTD4 is catalyzed by at least two enzymes, and
      a major part of the conversion is induced by MDP.

PMID- 12506054
TI  - Expression of beta-carotene 15,15' monooxygenase in retina and RPE-choroid.
AB  - PURPOSE: Beta-carotene 15,15' monooxygenase (beta-CM) catalyzes the central
      cleavage of beta-carotene to all-trans-retinal, the first step in vitamin A
      synthesis. This study was conducted to determine the expression of beta-CM in the
      mammalian retina and RPE, to assess its relevance in carotenoid-retinoid
      metabolism in the retina and RPE. METHODS: RT-PCR was used to detect expression
      of beta-CM mRNA in the retina and RPE-choroid of the mouse, cow, human, and
      monkey and in RPE cells and other cell lines. Immunofluorescence microscopy was
      used to localize beta-CM in mouse and monkey retina with an anti-peptide antibody
      specific for beta-CM. RESULTS: By RT-PCR, beta-CM mRNA was detected at a low
      level in mouse and monkey retina and in the RPE-choroid of the monkey but not of
      the mouse. Conversely, beta-CM mRNA was expressed at a low level in both human
      and bovine RPE-choroid, but not in the retina of either. RPE primary cultured
      cells of the monkey also showed beta-CM mRNA expression, although the three human
      lines did not. In addition, of nine other cell lines tested, only COS-7 was
      positive for beta-CM. Immunofluorescence microscopy showed weak immunoreactivity
      in the inner retina in both the mouse and monkey. beta-CM immunoreactivity was
      not detectable in RPE of the mouse. Use of a long-wavelength exciting and
      emitting secondary probe to mitigate lipofuscin autofluorescence, facilitated the
      detection of a low level of beta-CM immunoreactivity in monkey RPE. CONCLUSIONS:
      Beta-CM mRNA and protein are expressed at low levels in the mammalian retina and
      RPE-choroid. Given the low and variable expression of beta-CM in the retina and
      RPE, it can be concluded that beta-CM is not necessary for a conserved retina or
      RPE-specific function, but may be necessary for a species-specific function.

PMID- 12506055
TI  - Regulation of estrogen receptors and MMP-2 expression by estrogens in human
      retinal pigment epithelium.
AB  - PURPOSE: Age-related macular degeneration (ARMD) is characterized by progressive
      thickening and accumulation of various lipid-rich extracellular matrix (ECM)
      deposits under the retinal pigment epithelium (RPE). ECM dysregulation probably
      contributes to the pathologic course of ARMD. By activating estrogen receptors
      (ERs), estrogens regulate the expression of genes relevant in the turnover of
      ECM, among them matrix metalloproteinase (MMP)-2. Estrogen deficiency may
      predispose to dysregulated synthesis and degradation of ECM, leading to
      accumulation of collagens and other proteins between the RPE and its basement
      membrane. The purposes in the current study were to confirm the expression of ERs
      in human RPE, to elucidate whether these ERs are functional, and to test whether
      17beta-estradiol (E(2)) regulates expression of ERs and MMP-2. METHODS:
      Expression of ERs was examined in freshly isolated human RPE monolayer and in
      cultured human RPE cells, by using total RNA for RT-PCR and protein extracts for
      Western blot analysis. Supernatants were collected from freshly isolated human
      RPE and from cultured human RPE to assess MMP-2 activity by zymography and
      protein expression by Western blot. The transcriptional activity of ERs was
      studied in transfection experiments with an estrogen-responsive reporter
      construct. All these studies were preformed in the presence or absence of E(2)
      (10(-11) and 10(-7) M). RESULTS: Human RPE isolated from female and male
      individuals expressed both ER subtypes alpha and beta at the mRNA and protein
      levels. Treatment of cultured RPE cells with 10(-10) M E(2) increased expression
      of mRNA and protein of both receptor subtypes. E(2) (10(-10) M) also increased
      MMP-2 activity (approximately 2.2-fold) and protein expression (approximately 2.5
      fold). In contrast, there was no change in ER levels and MMP-2 activity at higher
      E(2) concentrations (10(-8) M), compared with baseline. Preincubation of cells
      with 10(-7) M pyrrolidinedithiocarbamate (PDTC), an inhibitor of nuclear factor
      (NF)-kappaB, abolished the increase in MMP-2 activity and protein expression
      induced by E(2) at 10(-10) M. CONCLUSIONS: Both ER subtypes are expressed in RPE
      and regulated in a dose-dependent fashion by E(2). Estrogens similarly regulate
      MMP-2. This estrogen-induced effect is, at least in part, mediated through NF
      kappaB. These data support the hypothesis that estrogens may exert biological
      function in RPE through ERs and that estrogen deficiency or excess may cause
      dysregulation of molecules that influence the turnover of ECM in Bruch's membrane
      associated with ARMD.

PMID- 12506056
TI  - Fenestrations enhance tear mixing under silicone-hydrogel contact lenses.
AB  - PURPOSE: Extended wear of conventional hydrogel soft contact lenses (SCLs) is
      associated with adverse ocular responses. Some of these ocular events are thought
      to result from inadequate tear mixing in the postlens tear film (PoLTF).
      Therefore, strategies to increase tear mixing may improve the safety of extended
      wear SCLs. Recently, it has been suggested that placing fenestrations in soft
      lenses increases tear mixing. In the present study, hydrodynamic modeling and
      tear-mixing measurements were used to explore the effects of fenestrations on
      tear exchange under an SCL. METHODS: Tear mixing, expressed as the time to
      deplete 95% of fluorescent dye from the PoTLF (T(95)), was measured in 20
      subjects fitted with two pairs of silicone hydrogel SCLs. The lenses were
      identical except that one pair was fenestrated (F) with 40 holes each 100 microm
      in diameter. The effect of fenestrations on improving tear mixing is explained
      and enhancement of tear mixing is predicted, with the use of hydrodynamic
      modeling. RESULTS: T(95) estimates were significantly lower (P < 0.001) in the F
      (mean T(95) = 18.3 minutes) lenses compared with the standard unfenestrated (S
      uF) (mean T(95) = 22.6 minutes) lenses (DeltaT(95) = 4.3 minutes, 95% CI = 2.5
      6.2) and were in general agreement with the proposed mixing model. Optimization
      of tear mixing can be achieved by selectively placing fenestrations in the
      pooling regions before the thinnest regions. The model predictions were sensitive
      to the distribution of tear-film thickness under the lens. CONCLUSIONS:
      Fenestrations improve tear-mixing efficiency. Accurate prediction of the effects
      of lens parameters on tear mixing, however, demands quantitative measurement of
      the postlens distribution of tear-film thickness.

PMID- 12506057
TI  - Thickness of the pre- and post-contact lens tear film measured in vivo by
      interferometry.
AB  - PURPOSE: To evaluate an interferometric method for measuring the thickness of the
      pre- (PLTF) and postlens tear film (POLTF) in subjects wearing hydrogel contact
      lenses. The precision and accuracy of measuring postlens tear thickness is
      compared with a previous method based on optical pachymetry and mechanical
      measurement of contact lens thickness. METHODS: Reflectance spectra (562-1030 nm)
      from the front of an eye wearing a contact lens were measured at normal
      incidence. Interference between reflections from four surfaces--the front of the
      tear film, the front and back of the contact lens, and the front of the cornea-
      can give rise to as many as six oscillations in the reflectance spectra, three
      from simple layers (layer A: PLTF; B, POLTF; C, contact lens) and three from
      composite layers, (layer D, A+C; layer E, C+B; layer F, A+C+B). The thickness of
      any layer is derived from the frequency of the oscillations. The principle of the
      method was tested with a rigid contact lens, which was designed to give distinct
      thicknesses for all six layers. Twenty spectra were then recorded from each of 12
      subjects wearing hydrogel contact lenses. RESULTS: The PLTF thickness averaged
      2.31 microm. There was good agreement between a direct estimate from layer A and
      an indirect estimate: layer D minus layer C. For POLTF, an indirect estimate-
      layer F minus layer D--averaged 2.34 microm and was more satisfactory than the
      direct estimate from layer B. There was no correlation between PLTF and POLTF
      thickness, showing that these are independent measurements, despite the
      similarity of their means. CONCLUSIONS: Prelens tear thickness was in reasonable
      agreement with prior measurements. Postlens tear thickness was much less than the
      11 to 12 microm found by the pachymetric method. It is argued that the current
      method avoids some of the systematic errors of the pachymetric method and also
      has much higher precision.

PMID- 12506058
TI  - Expression of type XVIII collagen during healing of corneal incisions and
      keratectomy wounds.
AB  - PURPOSE: To determine the distribution of type XVIII collagen in mouse ocular
      tissues and to investigate the expression of type XVIII collagen during healing
      of corneal incisions and keratectomy wounds. METHODS: Immunohistochemical
      analysis of type XVIII collagen was performed in mouse ocular tissue, with
      polyclonal antibodies to the hinge domain. For wound-healing experiments, excimer
      laser keratectomy and single linear incisions were performed on mouse corneas.
      The corneas were harvested at various time points after wounding and processed
      for immunohistochemistry, in situ hybridization, competitive reverse
      transcription-polymerase chain reaction (RT-PCR), and Western blot analysis.
      RESULTS: In the unwounded mouse cornea, type XVIII collagen was expressed by the
      corneal epithelial cells. Type XVIII collagen was immunolocalized to the mouse
      corneal epithelium, epithelial basement membrane, Descemet's membrane, ciliary
      epithelium, lens capsule, retinal inner limiting membrane, and Bruch's membrane.
      In the early stages of wound healing after excimer laser keratectomy (days 3 and
      7), type XVIII collagen staining of the epithelial basement membrane was absent,
      whereas its localization to Descemet's membrane was unchanged. After linear
      corneal incisions, however, type XVIII collagen was clearly seen in the stroma
      and in the epithelial basement membrane. Type XVIII collagen immunolocalization
      to the subepithelial stromal wound region peaked at 1 week after wounding, and
      its mRNA showed a corresponding temporal increase in expression within the same
      region after linear corneal incisions. CONCLUSIONS: The results suggest that type
      XVIII collagen is broadly expressed in ocular tissues and that it may have a role
      in wound healing, especially after incisional corneal wounds.

PMID- 12506059
TI  - The cell-layer- and cell-type-specific distribution of GalNAc-transferases in the
      ocular surface epithelia is altered during keratinization.
AB  - PURPOSE: It has been hypothesized that the biosynthesis of O-linked glycans on
      proteins, particularly on the highly O-glycosylated mucins, by the corneal and
      conjunctival epithelium is necessary for the protection and maintenance of a
      healthy ocular surface. The initial step in O-glycosylation is the enzymatic
      addition of N-acetyl galactosamine (GalNAc) to serine and threonine residues by a
      large family of polypeptide GalNAc-transferases (GalNAc-Ts). The purpose of this
      study was to determine the cellular distribution of GalNAc-Ts in the normal
      ocular surface epithelia and to compare their distribution with that in
      pathologically keratinized conjunctival epithelia. METHODS: Five conjunctival
      biopsy specimens and 5 corneas from normal individuals, and 14 conjunctival
      specimens from patients with ocular cicatricial pemphigoid (OCP) were used. Based
      on the histologic characteristics of their epithelia, OCP specimens were divided
      into two groups: less advanced, nonkeratinized (n = 6), and late-stage,
      keratinized (n = 8). Five monoclonal antibodies raised against the GalNAc-T1, 
      T2, -T3, -T4, and -T6 isoenzymes, were used for immunofluorescence microscopic
      localization according to standard protocols. RESULTS: Immunohistochemical
      studies revealed the presence of GalNAc-T2, -T3, and -T4 isoforms within the
      stratified epithelium of the cornea and the conjunctiva. The GalNAc-T4 isoenzyme
      was found in the apical cell layers, whereas GalNAc-T2 was found in the
      supranuclear region of the basal cell layers of both cornea and conjunctiva.
      GalNAc-T3 was distributed throughout the entire ocular surface epithelium,
      whereas GalNAc-T1 was found in scattered cells in conjunctiva only. Binding of
      antibody to GalNAc-T6 was restricted exclusively to conjunctival goblet cells.
      There were distinct alterations in expression patterns of GalNAc-T2, -T6, and -T1
      in nonkeratinized OCP epithelia compared with normal epithelia. Both GalNAc-T2
      and -T6 were expressed in the apical stratified epithelia, and T1 was detected in
      all cell layers in five of six biopsy specimens. By comparison with
      nonkeratinized OCP epithelia, a marked reduction in the binding of GalNAc-T
      antibody was observed in the late-stage keratinized conjunctival epithelia of
      patients with OCP. In all samples, apical GalNAc-T2 was absent, and GalNAc-T6 was
      entirely absent. Only one of eight samples was positive for GalNAc-T1.
      CONCLUSIONS: The presence of GalNAc-T isoenzymes in the human corneal and
      conjunctival epithelia is cell-layer and cell-type specific. The increased
      distribution of GalNAc-Ts observed in early stages of the keratinization process
      in patients with OCP suggests a compensatory attempt of the ocular surface
      epithelium to synthesize mucin-type O-glycans to maintain a wet-surface
      phenotype. This early increase in isoenzymes in nonkeratinized OCP epithelia is
      reduced as keratinization proceeds in the disease.

PMID- 12506060
TI  - FasL-Fas interactions regulate neovascularization in the cornea.
AB  - PURPOSE: Neovascularization of the avascular cornea is a significant problem
      associated with many corneal diseases. Because Fas ligand (FasL) is highly
      expressed in the cornea, the role of this molecule in controlling corneal
      neovascularization was examined in this study. METHODS: C57BL/6(B6), FasL (CD95L)
      deficient B6-gld, and Fas (CD95)-deficient B6-lpr mice were subjected to the
      suture model of neovascularization. Corneas were evaluated for neovascularization
      and representative samples subjected to immunohistochemical analysis for
      expression of Fas antigen and CD31 (platelet-endothelial cell adhesion molecule
      [PECAM-1]) on vessels that were present in the tissue. Corneas were also
      explanted and placed in collagen gel cultures to test the ability of anti-Fas
      antibody to prevent vessel extension from explanted corneas. RESULTS:
      Immunohistochemical data demonstrated that quiescent vessels express CD31 alone,
      whereas vessels that penetrate the cornea coexpressed both the Fas antigen and
      CD31. A significant increase was observed in neovascularization in FasL-deficient
      B6-gld corneas compared with B6 corneas, and new vessel growth in both B6 and B6
      gld was inhibited by anti-Fas antibody. Whereas Fas-deficient B6-lpr corneas
      displayed significantly less neovascularization than normal B6, B6-lpr mice
      express Fas on growing vessels. In corneal explant cultures, vessel growth from
      B6 and lpr mice corneas was inhibited by anti-Fas antibody, confirming functional
      Fas expression in B6-lpr mice. CONCLUSIONS: These data indicate that FasL is an
      important factor in controlling corneal neovascularization.

PMID- 12506061
TI  - Human corneal epithelial cells express functional PAR-1 and PAR-2.
AB  - PURPOSE: The objective of this study was to examine whether HCECs express
      functional proteinase-activated receptor (PAR)-1 and -2 and evaluate the effects
      of receptor activation on corneal epithelial cell proinflammatory cytokine
      production. METHODS: Expression of PAR-1 and -2 mRNAs was determined by RT-PCR in
      cultured primary human corneal epithelial cells (HCECs) and the human corneal
      epithelial cell line HCE-T. Localization of PAR-1 and -2 in whole normal human
      corneas was determined by immunofluorescence with PAR-1 and -2 antibodies. The
      functional competence of PAR-1 and -2 in corneal epithelial cells was assessed by
      measuring the rapid induction of intracellular [Ca(2+)] in response to thrombin,
      trypsin, and specific receptor-activating peptides derived from the tethered
      ligands of the PAR receptors. HCE-T expression of cytokines (IL-6, IL-8, and
      TNFalpha) in response to activation of PAR-1 and -2 was measured by quantitative
      RT-PCR and ELISA. RESULTS: Functional PAR-1 and -2 were expressed in both HCECs
      and HCE-T cells. Immunoreactivity for PAR-1 and -2 was detected in the outer
      epithelial layer of the cornea in whole human corneal sections. Activation of PAR
      1 and -2 led to upregulation in HCE-T cells of both expression of mRNA and
      secretion of the proinflammatory cytokines IL-6, IL-8, and TNFalpha. CONCLUSIONS:
      The results show for the first time that functional PAR-1 and -2 are present in
      human cornea. Activation of these receptors results in the production of various
      corneal epithelial cell proinflammatory cytokines. These observations indicate
      that PAR-1 and -2 may play an important role in modulating corneal inflammatory
      and wound-healing responses. These receptors may be useful therapeutic targets in
      several corneal disease processes.

PMID- 12506062
TI  - The successful culture and autologous transplantation of rabbit oral mucosal
      epithelial cells on amniotic membrane.
AB  - PURPOSE: To determine the feasibility of using human amniotic membrane (AM) as a
      substrate for culturing oral epithelial cells and to investigate the possibility
      of using autologous cultivated oral epithelial cells in ocular surface
      reconstruction. METHODS: An ocular surface injury was created in one eye of each
      of eight adult albino rabbits by a lamellar keratectomy, and a conjunctival
      excision was performed, including and extending 5 mm outside the limbus. Oral
      mucosal biopsy specimens were obtained from these eight adult albino rabbits and
      cultivated for 3 weeks on a denuded AM carrier. The cultivated epithelium was
      examined by electron microscopy (EM) and immunohistochemically labeled for
      several keratins. At 3 to 4 weeks after the ocular surface injury, the
      conjunctivalized corneal surfaces of the eight rabbits were surgically
      reconstructed by transplanting the autologous cultivated oral epithelial cells on
      the AM carrier. RESULTS: The cultivated oral epithelial sheet had four to five
      layers of stratified, well-differentiated cells. EM revealed that the epithelial
      cells were very similar in appearance to those of normal corneal epithelium, had
      numerous desmosomal junctions, and were attached to a basement membrane with
      hemidesmosomes. Immunohistochemistry confirmed the presence of the keratin pair 4
      and 13 and keratin-3 in the cultivated oral epithelial cells. Corneas that were
      grafted with the cultivated oral epithelial cells on an AM carrier were clear and
      were all epithelialized 10 days after surgery. CONCLUSIONS: Cultures of oral
      epithelial cells can be generated to confluence on AM expanded ex vivo from
      biopsy-derived oral mucosal tissue. Autologous transplantation was performed with
      these cultivated oral epithelial cells onto the ocular surfaces of keratectomized
      rabbit eyes. Autologous transplantation of cultivated oral epithelium is a
      feasible method for ocular surface reconstruction. The long-term outcome of such
      transplantation is not yet clear, and its feasibility in clinical use should be
      evaluated further.

PMID- 12506063
TI  - VEGF-dependent conjunctivalization of the corneal surface.
AB  - PURPOSE: To investigate the mechanisms governing corneal neovascularization and
      the appearance of goblet cells in a murine model of limbal insufficiency.
      METHODS: The spatial and time-dependent relationship between corneal
      neovascularization and goblet cell density was analyzed in corneal flatmounts.
      Immunohistochemical detection of the vascular endothelial growth factor (VEGF)
      receptor Flt-1 (VEGFR1) was performed in paraffin-embedded sections. A transgenic
      mouse that expresses the reporter gene lacZ targeted to the Flt-1 locus through
      homologous recombination was used to analyze corneal expression of Flt-1. The
      presence of soluble and membranous goblet cell Flt-1 mRNA and protein content was
      assessed with Northern and Western blot analyses, respectively. Finally, systemic
      adenoviral expression of a soluble Flt-1/Fc construct was used to study the
      effect of inhibition of VEGF bioactivity on the appearance of goblet cells and
      neovascularization. RESULTS: Corneal neovascularization preceded the appearance
      of goblet cells, although both processes overlapped temporally. Flt-1 was
      abundant in the conjunctiva-like epithelium covering the cornea, as well as in
      the goblet cells, invading leukocytes, and vasculature. A similar expression
      pattern was observed in the transgenic mice expressing the lacZ gene downstream
      from the Flt-1 promoter. Isolated human and rat goblet cells in culture expressed
      Flt-1 mRNA and protein, as did freshly isolated human conjunctiva. The systemic
      inhibition of VEGF bioactivity potently suppressed both corneal
      neovascularization (8.3% +/- 8.1% vs. 41.1% +/- 15.3% corneal area; P < 0.001)
      and corneal goblet cell density (1.6% +/- 2.5% vs. 12.2% +/- 2.4% corneal area; P
      < 0.001). CONCLUSIONS: Two important features of corneal conjunctivalization, the
      appearance of goblet cells and neovascularization, are regulated by VEGF. Both
      processes are probably mediated, in part, through the Flt-1 receptor. Taken
      together, these data indicate that an anti-VEGF therapeutic approach may limit
      the visual loss associated with conjunctivalization of the corneal surface.

PMID- 12506064
TI  - Apoptosis of ocular surface cells in experimentally induced dry eye.
AB  - PURPOSE: To evaluate to effect of experimental dry eye on ocular surface
      apoptosis. METHODS: Aqueous tear production and clearance were inhibited by
      systemic administration of scopolamine and exposure to an air draft for 12 days
      in 4- to 6-week-old 129SvEv/CD-1 mixed white mice. Eyes and ocular adnexa were
      excised, cryosectioned, and evaluated for apoptosis by terminal deoxynucleotidyl
      transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay,
      immunohistochemical assay for caspase-3 and poly(ADP-ribose) phosphate (PARP),
      and examination of nuclear morphologic changes by Hoechst DNA nuclear staining
      and transmission electron microscopy. RESULTS: The number of TUNEL-positive cells
      in the mice with induced dry eye was significantly increased compared with
      control mice in the following ocular regions: central corneal (P < 0.0014),
      peripheral corneal (P < 0.0001), bulbar conjunctival (P < 0.0021), and tarsal
      conjunctival (P < 0.0046) epithelia; tarsal conjunctival stroma (P < 0.0274); and
      lid margin (P < 0.0219, n = 4 in all cases). There were no significant
      differences observed between treated and control groups in the central corneal,
      peripheral corneal, or bulbar conjunctival stroma; meibomian glands; skin; retina
      choroid; or episcleral regions. Immunohistochemistry for caspase-3 and poly(ADP
      ribose) polymerase p85 fragment revealed increased immunoreactivity in regions of
      increased TUNEL positivity, particularly in the corneal and conjunctival
      epithelial cells. Ultrastructural morphologic changes consistent with apoptosis
      were observed in the conjunctival epithelial cells. CONCLUSIONS: Experimentally
      induced dry eye in mice causes apoptosis of cells in ocular surface tissues
      including the central and peripheral corneal epithelium, bulbar and tarsal
      conjunctival epithelia, tarsal conjunctival stroma, and lid margin. Apoptosis may
      play a key role in the pathogenesis of keratoconjunctivitis sicca and may be a
      therapeutic target for this condition.

PMID- 12506065
TI  - Collagen organization in the secondary chick cornea during development.
AB  - PURPOSE: The latter stages of morphogenesis in the embryonic chick cornea are
      instrumental in the establishment of a properly formed corneal stroma. This study
      was designed to provide better appreciation of collagen reorganization in the
      avian corneal stroma during the latter stages of embryogenesis. METHODS: High
      angle synchrotron x-ray diffraction patterns were obtained from 47 developing
      chick corneas daily at developmental days 13 through 18 (n = 7 or 8 at each time
      point) and analyzed to establish collagen molecular spacing and fibril
      orientation. RESULTS: Collagen intermolecular x-ray reflections were of
      approximately constant intensity between days 13 and 15 of development, but
      thereafter became progressively more intense, suggesting that extra collagen is
      deposited in embryonic chick corneas after day 16 of development. At all times,
      the mean collagen intermolecular spacing measured approximately 1.43 nm. X-ray
      intensity was not uniform around the intermolecular x-ray reflections at earlier
      time points. Rather, a fourfold symmetry was evident, indicative of an orthogonal
      array of collagen fibrils. An index of this symmetry was essentially unchanged
      between developmental days 13 and 15, but thereafter diminished considerably.
      CONCLUSIONS: The lateral spacing of fibril-forming collagen molecules does not
      change as the chick cornea develops between days 13 and 18. An orthogonal array
      of collagen fibrils is present in the corneas of developmental day-13 to -18
      chicks, but starting at developmental day 16, additional collagen is deposited in
      a less well-oriented manner and thus acts to obscure the overall orthogonality,
      with implications for the biomechanical strength and shape of the cornea.

PMID- 12506066
TI  - Corneal neovascularization after excimer keratectomy wounds in matrilysin
      deficient mice.
AB  - PURPOSE: Matrilysin, matrix metalloproteinase (MMP)-7, is upregulated in the
      corneal epithelium during wound healing after excimer keratectomy wounds. The
      purpose of this study was to determine the role of matrilysin in maintaining
      corneal avascularity during wound healing. METHODS: Matrilysin-deficient mice (n
      = 17) and their age-matched wild-type littermates (n = 18) were treated with 193
      nm argon-fluoride excimer keratectomy (experiment I). The percentage of corneal
      surface occupied by neovascularization was measured with a computer image
      analysis program adjusted for parallax. In another experiment (experiment II),
      epithelial closure was monitored with slit lamp biomicroscopy and fluorescein
      staining, and corneal neovascularization was confirmed by india ink perfusion,
      electron microscopy, and immunolocalization of CD31 and type IV collagen. Corneal
      micropocket assays were performed to compare the area of corneal
      neovascularization in matrilysin-deficient mice and wild-type littermates
      (experiment III). To determine whether the differences in corneal
      neovascularization were related to differences in angiogenic factors, the levels
      of basic fibroblast growth factor (bFGF) were compared with those of vascular
      endothelial growth factor (VEGF) in matrilysin-deficient and wild-type mouse
      corneas (experiment IV). RESULTS: The percentages of the corneal surface occupied
      by neovascularization after excimer laser keratectomy in the matrilysin-deficient
      mice measured 21.3% +/- 5.2% and 18.7% +/- 5.8% at days 3 and 7, respectively,
      compared with 5.3% +/- 2.4% and 5.5% +/- 3.4% in the wild-type littermates at
      days 3 (P < 0.01) and 7, respectively (P < 0.05; experiment I). No significant
      differences in the rates of epithelial closure of corneal wounds were observed
      between matrilysin-deficient and wild-type mice after wounding. Corneal
      neovascularization in the matrilysin-deficient mice was confirmed by india ink
      present in the corneal stromal blood vessels (extending from the limbus to the
      wound), immunohistochemical staining, and electron microscopy. Gram, Giemsa,
      calcofluor white, and acridine orange stains and electron microscopy showed no
      evidence of corneal infection (experiment II). The area of corneal
      neovascularization in matrilysin-deficient mice was not significantly different
      from that of wild-type littermates after implantation of bFGF pellets (0.91 +/-
      0.55 mm(2) and 0.77 +/- 0.34 mm(2), respectively; experiment III). The levels of
      bFGF and VEGF (VEGF, VEGF-B, and VEGF-C) in corneal epithelial cells were not
      elevated in matrilysin-deficient mice compared with the wild-type mice
      (experiment IV). CONCLUSIONS: Matrilysin may play an important role in
      maintaining corneal avascularity during wound healing. The differences in corneal
      neovascularization between matrilysin-deficient mice and wild-type littermates
      seem unrelated to the bFGF and VEGF levels in the corneal epithelium.

PMID- 12506067
TI  - Static aspects of eye and head movements during reading in a simulated computer
      based environment with single-vision and progressive lenses.
AB  - PURPOSE: Reading with two different intermediate progressive lens designs was
      investigated regarding eye and head movement patterns and compared with movement
      patterns with a conventional single vision lens in a computer-based work
      environment. METHODS: Two-dimensional eye (horizontal, vertical) and three
      dimensional head (horizontal, vertical, and torsional) movements were recorded
      objectively and simultaneously at a rate of 60 Hz during reading of moderate
      contrast (40%) single- and double-page text formats at 60 cm with binocular
      viewing. In addition, global reading ability was rated subjectively for each
      lens. Subjects were 11 visually normal, presbyopic individuals aged 45 to 71
      years selected by convenience sampling from a clinic population. Reading was
      performed with three types of spectacle lenses: a single-vision lens (SVL; 60
      degrees horizontal [H] clear field-of-view [FOV]); a progressive addition lens
      (PAL) with a relatively wide intermediate zone (PAL-I; 7.85 mm, 18 degrees H
      clear FOV); and a PAL with a relatively narrow intermediate zone (PAL-II; 5.60
      mm, 13 degrees H clear FOV). RESULTS: Many reading-related parameters, as well as
      eye- and head-movement parameters, were adversely affected by the PALs compared
      with the SVL. One reading-related parameter (i.e., number of regressions)
      differentiated between PALs. Subjective rating of global reading ability was
      highest with the SVL and lowest with the PAL-II. CONCLUSIONS: The optical design
      of a spectacle lens had significant impact on reading performance and on the
      combined eye-head movements initiated during reading. Both horizontal eye and
      head movements discriminated well between PALs and the SVL, but not between PALs,
      despite subjective preferences. This suggests that nonoculomotor factors
      contribute to patients' nonacceptance of PALs. Vertical eye and head movements
      and torsional head movements were not as discriminatory as were their horizontal
      counterparts.

PMID- 12506068
TI  - Increase in dephosphorylation of the heavy neurofilament subunit in the monkey
      chronic glaucoma model.
AB  - PURPOSE: To investigate the phosphorylation of the heavy neurofilament subunit
      (NF-H), which could be deeply involved in axonal transport of retinal ganglion
      cells (RGCs), in an experimental glaucoma model of chronic elevation of
      intraocular pressure (IOP) in monkeys. METHODS: One eye in adult monkeys was
      randomly selected for laser treatment, and IOP was maintained between 30 and 40
      mm Hg throughout the experiment. The eyeballs with the optic nerve and optic
      chiasm were enucleated as one tissue and were subject to immunocytochemical
      observation, using two NF-H-specific antibodies, NF-200 and SMI31. NF-200 reacts
      with both phosphorylated and dephosphorylated NF-H, whereas SMI reacts only with
      phosphorylated NF-H. Ratios of SMI31-positive to NF-200-positive areas were
      calculated for quantitative evaluation of phosphorylation status. Specimens from
      the retina, lamina cribrosa (LC), post-LC, and optic chiasm were evaluated
      separately. Phosphorylation of NF-H at the retina and optic nerve head was
      compared between specimens from temporal retina and nasal retina, or between
      temporal and nasal regions of the optic disc. The status of phosphorylation was
      confirmed by Western blot analysis. RESULTS: An enlargement of the disc cup was
      observed on the temporal side, and the superior and inferior poles were
      preferentially involved in the neuronal damage in laser-treated eyes. Most NF-Hs
      in the control eyes were phosphorylated in all investigated regions, whereas
      those in the glaucomatous eyes were significantly dephosphorylated, and NF-Hs in
      the temporal region were significantly dephosphorylated compared with those in
      the nasal region. At the optic chiasm, NF-Hs in axons traveling from laser
      treated eyes were highly dephosphorylated, and the extent of NF-H
      dephosphorylation corresponded to the degree of glaucoma-induced axonal damage.
      Western blot analysis showed the change in the phosphorylation of NF-Hs.
      CONCLUSIONS: NF-Hs in RGC axons are dephosphorylated by elevated IOP, which may
      be deeply involved in glaucoma-induced damage to axonal transport.

PMID- 12506069
TI  - Optic disc imaging in conscious rats and mice.
AB  - PURPOSE: To determine whether useful images of the optic discs of conscious rats
      and mice can be obtained by using a photo slit lamp and a modified Goldmann-type
      fundus contact lens. METHODS: Testing was performed with a photo slit lamp
      equipped with two 2x teleconverters and a digital camera through a Goldmann-type
      fundus contact lens that was fabricated for the rodent eye. RESULTS: Images of
      the rat and mouse optic discs were obtained that are comparable to those used by
      ophthalmologists to assess optic neuropathy in glaucoma, a key part of the
      standard of care and of clinical investigation of this disease. The cup in the
      optic disc image of these rodents is darker than the neural rim of the disc,
      rather than lighter, as it is in humans. CONCLUSIONS: In addition to the
      application of this imaging method to studies of the effect on optic disc cupping
      of induced increased intraocular pressure in rats and mice, by detecting and
      documenting the onset and the course of optic neuropathy, it should be valuable
      in identifying animal models of glaucoma, in studying neuropathogenic mechanisms,
      and in assessing the effects of experimental therapies.

PMID- 12506070
TI  - Involvement of the Erk-MAP kinase pathway in TNFalpha regulation of trabecular
      matrix metalloproteinases and TIMPs.
AB  - PURPOSE: TNFalpha is a strong modulator expression of trabecular meshwork (TM)
      matrix metalloproteinase (MMP) and tissue inhibitor (TIMP). Laser trabeculoplasty
      appears to rely on this process to restore normal aqueous humor outflow facility.
      Thus, studies were conducted to determine whether the extracellular signal
      regulated kinase (Erk)-mitogen-activated protein (MAP) kinase signal-transduction
      pathway is involved. METHODS: Porcine TM cells were treated with TNFalpha, and
      changes in MMPs and TIMPs were evaluated by zymography and Western immunoblot
      assay. Phosphospecific antibodies to proteins from the Erk pathway were used to
      evaluate responses to treatment with TNFalpha. Inhibitors of Mek, the kinase that
      activates Erk, and of protein kinase C (PKC) isoforms were used to define pathway
      involvement. RESULTS: Treatment with TNFalpha increased MMP-1, -3, and -9 and
      TIMP-1, whereas expression of MMP-2 was not affected and expression of TIMP-2 was
      decreased. Erk and Mek were rapidly phosphorylated after treatment with TNFalpha,
      and c-Raf-1 showed a significant bandshift. A specific inhibitor of Mek blocked
      the TNFalpha induction of the MMPs and TIMPs and the phosphorylation of Erk. An
      inhibitor of the PKC- micro isoform, which also blocks the effects of MMP-TIMP of
      TNFalpha, did not affect phosphorylation of Erk. CONCLUSIONS: The components of
      this MAP kinase pathway in the TM are dramatically affected by TNFalpha and
      inhibition of Erk's phosphorylation blocks the changes in MMP and TIMP
      expression. PKC micro, which is also required in this transduction process, does
      not appear to be upstream from Erk in the signaling cascade. Manipulation of this
      and related TM signal-transduction pathways may provide targets for developing
      improved glaucoma treatments.

PMID- 12506071
TI  - Influence of cilioretinal arteries on neuroretinal rim and parapapillary atrophy
      in glaucoma.
AB  - PURPOSE: The pattern of neuroretinal rim loss and increase in the area of
      parapapillary atrophy in glaucoma depend on the localization of the central
      retinal vessel trunk in the lamina cribrosa. The purpose of the present study was
      to determine whether, in a similar way, the pattern of rim loss and progression
      of parapapillary atrophy are influenced by the presence and position of
      cilioretinal arteries. METHODS: Color stereo optic disc photographs (15 degrees)
      for morphometric evaluation of the optic nerve head were used to compare the
      appearance of the optic disc in 41 patients exhibiting unilateral or bilateral
      cilioretinal arteries in the temporal horizontal disc region with the optic disc
      morphology of 127 patients without cilioretinal arteries. The areas of the
      neuroretinal rim and alpha and beta zones of parapapillary atrophy were measured
      in the total disc and in four disc sectors. RESULTS: Eyes with and eyes without
      cilioretinal arteries did not differ significantly in the areas of neuroretinal
      rim and alpha and beta zones of parapapillary atrophy, when measured in the whole
      optic disc and in the four disc sectors separately; in ratios of the temporal
      horizontal area to total area of rim and parapapillary atrophy; and in the ratio
      of temporal horizontal rim area-to-nasal rim area, neither in an interindividual
      comparison nor in an intraindividual intereye comparison. CONCLUSIONS: In
      contrast to the position of the central retinal vessel trunk, presence and
      position of cilioretinal arteries do not markedly influence the pattern of
      neuroretinal rim loss and progression of parapapillary atrophy in glaucoma.

PMID- 12506072
TI  - CD8+ T cell-mediated delayed rejection of orthotopic guinea pig cornea grafts in
      mice deficient in CD4+ T cells.
AB  - PURPOSE: To determine the immunopathogenesis of delayed orthotopic corneal
      xenograft rejection in mice deficient in the xenoreactive CD4+ T cells that
      mediate acute rejection. METHODS: CB.17 SCID and BALB/c mice were used as
      recipients of orthotopic cornea grafts obtained from strain 13 guinea pigs.
      Before transplantation, SCID recipients, which do not normally reject guinea pig
      cornea grafts, were reconstituted with spleen cells (whole, CD4-depleted, CD4/CD8
      depleted) or purified CD8+ T cells from normal BALB/c donors. Graft survival was
      assessed by clinical examination, and median survival times (MST) were
      calculated. Lymphocytes from mice that rejected guinea pig cornea grafts were
      analyzed in vitro for their capacity to respond to guinea pig xenoantigens and to
      lyse guinea pig target cells. RESULTS: SCID mice reconstituted with whole spleen
      cells from BALB/c donors rejected guinea pig corneas with a vigor identical with
      that of normal BALB/c mice (MST = 15 and 14 days, respectively), whereas SCID
      mice reconstituted with CD4-depleted BALB/c spleen cells rejected guinea pig
      corneas in a delayed fashion (MST = 27 days), as did SCID mice reconstituted with
      purified CD8+ T cells from BALB/c donors. Although CD8+ T cells from rejector
      mice failed to lyse guinea pig target cells in vitro, the T cells proliferated
      and secreted IFN-gamma in response to in vitro stimulation with guinea pig
      xenoantigens. CONCLUSIONS: Guinea pig cornea xenografts that avoid acute
      rejection in CD4+ T cell-depleted mice are vulnerable to rejection by CD8+ T
      cells. Effector CD8+ T cells destroy corneal xenografts through release of
      proinflammatory mediators (IFN-gamma) rather than by cytotoxicity.

PMID- 12506073
TI  - Effects of Th2 cytokines on expression of collagen, MMP-1, and TIMP-1 in
      conjunctival fibroblasts.
AB  - PURPOSE: To determine whether cytokines involved in chronic allergic conjunctival
      disorders may affect formation of giant papillae and tissue remodeling. METHODS:
      Conjunctival fibroblast cultures were challenged with different concentrations of
      human recombinant interleukin (IL)-4, IL-13, interferon (IFN)-gamma and tumor
      necrosis factor (TNF)-alpha. Procollagens I (PIP) and III (PIIIP), matrix
      metalloproteinase (MMP)-1 and -9, and tissue inhibitor of metalloproteinase
      (TIMP)-1 were measured in supernatants, and their respective mRNAs were evaluated
      by RT-PCR. RESULTS: IL-4 and -13 (10 ng/mL) significantly increased production
      and expression of PIP compared with nonstimulated cells, whereas IFN-gamma
      elicited the opposite effect, at both the protein and mRNA levels. Both IL-4 and 
      13 significantly decreased production of MMP-1 and increased that of TIMP-1,
      whereas TNF-alpha increased production of MMP-1 and -9. Expression of MMP-1 was
      reduced by IL-4 and increased by the other tested cytokines, whereas expression
      of TIMP-1 was increased by all tested cytokines. CONCLUSIONS: IL-4 and -13
      increased production of collagen and modified the equilibrium between MMP-1 and
      its inhibitor, TIMP-1. These effects were partially opposed by IFN-gamma and TNF
      alpha.

PMID- 12506074
TI  - Molecular analysis of Pseudomonas aeruginosa protease IV expressed in Pseudomonas
      putida.
AB  - PURPOSE: In this study, the protease IV gene of Pseudomonas aeruginosa was
      expressed in the nonocular pathogenic host, Pseudomonas putida, to elucidate the
      molecular properties and virulence contribution of the enzyme. Recent
      determination of the protease IV gene sequence suggests that the protein of 463
      amino acids contains a signal sequence, a propeptide domain, and a mature
      protease. The only form of this protein that has been detected previously is the
      extracellular mature protease. METHODS: The protease IV gene was cloned and
      expressed in a protease IV-negative Pseudomonas species, P. putida. The cloned
      protease IV gene product was analyzed to identify biochemical, enzymatic, and
      immunologic properties and its contribution to corneal virulence. RESULTS: P.
      putida expressing the cloned protease IV gene had significantly greater
      extracellular enzyme activity than P. aeruginosa. These P. putida cell extracts
      produced a protein with the same molecular mass as mature protease IV and two
      other polypeptides representing larger precursors, all of which were recognized
      by protease IV-specific antibodies. P. putida producing protease IV, relative to
      P. putida with the vector alone, caused a threefold increase in ocular
      inflammation and tissue damage when intrastromally injected into rabbit corneas.
      CONCLUSIONS: The present study demonstrates for the first time that protease IV
      is synthesized as a large precursor that is processed intracellularly through an
      intermediate form and secreted into the extracellular milieu as a mature
      protease. The results also confirm a significant correlation between production
      of protease IV and corneal virulence.

PMID- 12506075
TI  - Phospholipase A2 activity in normal and Staphylococcus aureus-infected rabbit
      eyes.
AB  - PURPOSE: To quantify phospholipase A(2) (PLA(2)) activity in normal rabbit eyes
      and in eyes with Staphylococcus aureus keratitis. METHODS: PLA(2) was assayed by
      the killing of S. aureus at 33 degrees C or by the release of arachidonic acid
      from S. aureus labeled with radioactive oleic acid. Rabbit corneas were
      intrastromally injected with 100 log phase colony-forming units (CFU) of S.
      aureus 8325-4. The activity of myeloperoxidase (MPO) and PLA(2) were quantified
      in ocular tissues. RESULTS: The PLA(2)-mediated killing of S. aureus by normal
      rabbit tears decreased by more than 70% as the rabbits aged from 10 to 28 weeks
      and by nearly 50% from early morning to afternoon. In rabbits with S. aureus
      keratitis, the activity of PLA(2) and MPO increased proportionally with time from
      5 to 25 hours postinfection (PI), as measured in ocular tissues. PLA(2) activity
      increased fivefold in tears from infected eyes collected at 25 hours PI compared
      with normal tears (P < or = 0.0001), whereas a ninefold increase was found in
      aqueous humor of infected eyes at 25 hours PI (P < or = 0.0001). Infected eyes
      demonstrated a significant increase in MPO activity compared with uninfected eyes
      beginning at 10 hours PI for the aqueous humor (P = 0.03), at 16 hours PI for the
      tear film (P = 0.0024) and at 22 hours PI for the corneal homogenate (P =
      0.0007). CONCLUSIONS: The decrease in PLA(2) activity in the rabbit eye with age
      or after sleep and its increase during sleep or with the progression of infection
      are consistent with its role as an innate host defense factor.

PMID- 12506076
TI  - BetaB1-crystallin: identification of a candidate ciliary body uveitis antigen.
AB  - PURPOSE: Perineuclear anti-neutrophil cytoplasmic antibody (pANCA), a marker
      antibody present in 12% of patients with anterior uveitis, recognizes cytoplasmic
      antigens in the nonpigmented ciliary body epithelium, a probable site of
      immunologic reactivity in this inflammatory disease. In this study, a
      recombinantly isolated pANCA monoclonal antibody was used to identify the
      corresponding antigenic target(s) in the ciliary body. METHODS: Proteins from
      microdissected eye bank ocular ciliary body tissue were used to identify the
      corresponding ANCA antigen. Parallel two-dimensional protein gels were used for
      simultaneous identification of candidate antigenic protein spots by Western blot
      analysis and as a source of material for proteomic analysis. Multiple independent
      methods including Western blot analysis, confocal microscopy, and RT-PCR were
      used to provide additional characterization of the candidate protein. RESULTS:
      Proteomic analysis suggested that beta B1 (betaB1)-crystallin is the primary
      ciliary body antigen. The presence of betaB1-crystallin in the human ciliary body
      was confirmed by Western blot with a betaB1 specific anti-peptide antibody.
      Confocal microscopy revealed colocalization of the antigenic reactivity of both
      anti-betaB1 antibody and monoclonal pANCA. RT-PCR confirmed the presence of
      betaB1-crystallin RNA in the ciliary body tissues. CONCLUSIONS: This study
      identified betaB1-crystallin as a new cytoplasmic ciliary body antigenic target
      of a marker autoantibody associated with uveitis. This characterization of betaB1
      crystallin outside the lens raises questions about its extralenticular
      expression, intracellular role, and potential target of inflammation in uveitis.

PMID- 12506077
TI  - Experimental keratomycosis in a mouse model.
AB  - PURPOSE: To establish a murine model of corneal candidiasis that permits
      molecular evaluation of fungal adherence and invasion. METHODS: Corneas of
      immunocompetent, methylprednisolone-treated, and cyclophosphamide-treated adult
      NIH Swiss and BALB/c mice were topically mock inoculated or inoculated with 10
      fold increasing amounts between 100 and 100 million colony-forming units (CFU) of
      Candida albicans after unilateral corneal scarification. Mock-inoculated eyes
      served as the control. Eyes were scored daily on a 12-point scale to categorize
      corneal inflammation and were enucleated for quantitative fungal cultures,
      analysis by polymerase chain reaction (PCR), and histopathologic examination.
      RESULTS: At least 100 CFU of C. albicans initiated measurable corneal infection,
      but 1 million or more colony-forming units were needed to induce consistent
      keratitis. Treatment with methylprednisolone increased disease severity in
      infected BALB/c mice and fungal persistence in both BALB/c and NIH Swiss mice.
      Treatment with cyclophosphamide increased disease severity and fungal persistence
      in both strains of mice. Infectious organisms were recovered by quantitative
      culture, and candidal DNA was detectable by PCR. C. albicans, inflammatory cells,
      and stromal necrosis were histologically evident within ocular tissue.
      CONCLUSIONS: Although mice are innately resistant to Candida infection after
      corneal inoculation, moderate to severe keratomycosis can be established in
      immunocompromised mice by the route of corneal scarification. Although
      differences between mouse strains and among immunosuppressive regimens remain to
      be explored, this murine model provides the basis for understanding the
      pathogenesis of fungal infections of the cornea.

PMID- 12506078
TI  - HSV1 latency sites after inoculation in the lip: assessment of their localization
      and connections to the eye.
AB  - PURPOSE: To localize the sites of HSV1 latency in mice after a primary infection
      induced by injection into the lip and to assess their connection to the eye.
      METHODS: The SC16 strain of HSV1, or a recombinant virus containing the HSV1
      latency-associated transcript (LAT)-promoter driving expression of the LacZ
      reporter gene, were injected into the left upper lip. Tissues from animals killed
      at 6, 28, 180, and 720 days postinoculation (dpi) were analyzed for LATs, either
      by in situ hybridization (ISH) or by identifying LAT-promoter-driven transgene
      expression. HSV1 antigens were detected by immunochemistry. RESULTS: At 28 dpi,
      all the neurologic structures that were acutely infected at 6 dpi exhibited a
      pattern of virus gene expression consistent with HSV1 latency--that is, LATs with
      no detectable HSV1 antigens. LAT staining differed among structures: intense and
      widespread within trigeminal neurons, intermediate within the sympathetic
      intermediolateral cell group of the spinal cord and the facial motor nucleus, and
      weak in other sites. Long-term expression of LATs (positive at 180 and 720 days)
      was observed only in tissues where the staining was intense or intermediate at 28
      dpi. CONCLUSIONS: After inoculation into the upper lip of mice, HSV1 established
      latency in several nervous system structures that have direct or indirect
      connections with ocular tissues. These results suggest that after an oral primary
      infection, the most frequent in humans, HSV1 may establish latency in several
      sites connected to the eye and may finally result in herpetic ocular disease
      involving the cornea, the iris, or even the retina.

PMID- 12506079
TI  - Leukocyte trafficking in experimental autoimmune uveitis: breakdown of blood
      retinal barrier and upregulation of cellular adhesion molecules.
AB  - PURPOSE: To clarify the order of events occurring in the breakdown of the blood
      retinal barrier (BRB) in experimental autoimmune uveoretinitis (EAU) and in
      particular to study the relationships between increased vascular permeability,
      upregulation of endothelial cell adhesion molecules, and leukocyte adhesion and
      infiltration during EAU. METHODS: B10.RIII mice were immunized with human
      interphotoreceptor retinoid binding protein (IRBP) peptide 161-180. Changes in
      the retinal microvasculature were examined on days 3, 6, 7, 8, 9, 10, 16, and 21
      postimmunization (pi). Evans blue dye was administered intravenously to assess
      vascular permeability. Expression of intercellular adhesion molecule (ICAM)-1,
      vascular cell adhesion molecule (VCAM)-1, P-selectin, E-selectin, and platelet
      endothelial cell adhesion molecule (PECAM)-1 was evaluated by in vivo
      administration of antibody and subsequent immunostaining of retinal wholemounts.
      Lymphocytes from inguinal lymph nodes of normal and chicken ovalbumin (OVA)- or
      IRBP peptide-immunized mice at day 5, 6, 7, 8, and 15 pi were labeled in vitro
      with calcein-AM (C-AM) and infused intravenously into syngeneic recipient mice,
      which had been immunized with peptide at the same corresponding time point.
      Wholemount preparations of retinas were observed 24 hours later by confocal
      microscopy to determine the adhesion and infiltration of lymphocytes. RESULTS:
      The first observation of an increase in vascular permeability occurred at day 7
      pi and was restricted to focal areas of the retinal postcapillary venules of the
      inner vascular plexus. This progressively extended to the outer vascular plexus
      at day 9 pi. Specific adhesion of leukocytes to the endothelium of retinal
      venules of the inner vascular plexus was first observed at day 6 pi. Leukocyte
      extravasation into the retinal parenchyma from these vessels began at day 8 pi
      and extended to the outer vascular plexus at day 9 pi. The expression of adhesion
      molecules increased progressively during the development of EAU. In particular,
      the adhesion molecules ICAM-1, P-selectin, and E-selectin were expressed
      predominately in retinal venules, the sites of BRB breakdown, cell adhesion, and
      extravasation, from day 7 pi. The increases in expression of ICAM-1 and P
      selectin were associated both spatially and temporally with breakdown of the BRB,
      cell adhesion, and extravasation. No increase in expression of P-selectin and
      ICAM-1 was observed in either the mesenteric vessels of EAU mice or the retinal
      vessels of OVA-immunized mice. CONCLUSIONS: The sequence of events in EAU appears
      to be focal adhesion of leukocytes to discrete sites on postcapillary venules,
      followed by upregulation of adhesion molecules, especially ICAM-1 and P-selectin,
      and breakdown of the BRB, leading to transendothelial migration of leukocytes and
      recruitment of large numbers of cells to the retinal parenchyma. These changes
      occur over a short period of 6 to 9 days pi and initiate the process of tissue
      damage during the following 2 to 3 weeks.

PMID- 12506080
TI  - Isolation and characterization of the human CP49 gene promoter.
AB  - PURPOSE: This study focuses on the identification of regulatory elements that
      contribute to lens-specific expression of the human CP49 gene within the 5'
      flanking DNA sequences. METHODS: The DNA sequence upstream of the human CP49
      coding region was subcloned as a set of 5' and 3' deletion series. The constructs
      were transfected into lens (N/N1003A) and nonlens (NIH3T3) cell lines and chicken
      primary lens cultures, to test for promoter activity and specificity. To further
      test the specificity, a portion of the 5' flanking DNA sequence was used to drive
      transgene expression in mice. The flanking DNA sequence was analyzed for
      potential transcription factor-binding sites. RESULTS: The 5'-flanking DNA
      preferentially activated reporter gene expression in a lens-preferred manner when
      transfected into cultured cells. Transgene expression driven by the CP49 promoter
      region was lens specific. Analysis of the proximal promoter sequence revealed the
      presence of potential binding sites for the AP-1, AP-2, and OCT-1 transcription
      factors and the absence of TATA and CAAT boxes. CONCLUSIONS: The sequence
      upstream of the CP49 gene possesses promoter activity and is able to drive lens
      preferred expression in both transfection and transgenic experiments. Promoter
      activity is dependent on the presence of the proximal 300 bp directly upstream of
      the coding region.

PMID- 12506081
TI  - Electric fields and MAP kinase signaling can regulate early wound healing in lens
      epithelium.
AB  - PURPOSE: To use lens epithelial cell monolayer wounds as a model system for the
      aberrant cell migration underlying posterior capsule opacification (PCO) and to
      investigate the effects of an applied physiological electric field (EF) on
      monolayer wound healing. METHODS: Scratch wounds were made in cultured bovine
      lens epithelial monolayers, and the wounds were exposed to an EF, with or without
      U0126 treatment (an inhibitor of active extracellular signal-regulated kinase
      [ERK 1/2]). Serial wound images were taken and wound areas were measured. Western
      blot analysis and immunocytochemical staining for ERK 1/2 in the wounded
      monolayers were performed. RESULTS: An applied EF of a given polarity influenced
      the healing of lens epithelial monolayer wounds. Wounds facing the anode healed
      at normal rates, those facing the cathode closed much more slowly. U0126, an
      inhibitor of mitogen-activated protein kinase (MAPK) signaling, inhibited wound
      healing, with or without exposure to an EF. Western blot analysis showed that
      both wounding and application of an EF enhanced the activation of ERK 1/2
      independently and that U0126 completely inhibited these activations of ERK 1/2 in
      monolayers. Immunocytochemical staining showed an asymmetric activation of ERK
      1/2 in EF-exposed wounds, with much weaker fluorescence in cathode-facing wounds,
      which could contribute to differentially directed wound-healing rates in an EF.
      CONCLUSIONS: Exposure to an EF inhibited the healing of lens epithelial monolayer
      wounds facing the cathode. ERK signaling pathways were involved in healing of
      lens epithelial monolayer wounds and in the EF-directed migration of the wound
      edge. It may be possible to use an applied EF to regulate the aberrant migration
      of lens epithelial cells that results in PCO after cataract surgery.

PMID- 12506082
TI  - Polymer refilling of presbyopic human lenses in vitro restores the ability to
      undergo accommodative changes.
AB  - PURPOSE: Because presbyopia is thought to be accompanied by increased lens
      sclerosis this study was conducted to investigate whether refilling the capsule
      of the presbyopic human lens with a soft polymer would restore the ability of the
      lens to undergo accommodative changes. METHODS: Accommodative forces were applied
      to natural and refilled lenses by circumferential stretching through the ciliary
      body and zonular complex. Nine natural lenses and 10 refilled lenses from donors
      ranging in age from 17 to 60 years were studied. Two refill polymers with a
      different Young's modulus were used. The lens power was measured by a scanning
      laser ray-tracing technique, and lens diameter and lens thickness were measured
      simultaneously while the tension on the zonules was increased stepwise by outward
      pull on the ciliary body. RESULTS: In the natural lenses the older lenses were
      not able to undergo power changes with stretching of the ciliary body, whereas in
      the refilled lenses, all lenses showed power changes comparable to young, natural
      lenses. The refilled human lenses had a higher lens power than the age-matched
      natural lenses. The Young's modulus of the polymers influenced the lens power
      change when measured with the ciliary body diameter increased by 4 mm.
      CONCLUSIONS: Refilling presbyopic lenses with a soft polymer enabled restoration
      of lens power changes with mechanical stretching. Because sclerosis of the lens
      is an important factor in human presbyopia, refilling the lens during lens
      surgery for cataract could enable restoration of clear vision and accommodation
      in human presbyopia.

PMID- 12506083
TI  - Syneretic response of aging normal human lens to pressure.
AB  - PURPOSE: The study was designed to observe whether a reversible syneretic
      response to pressure is operative in normal human lenses and whether such a
      response demonstrates a uniform age dependence. METHODS: Seven sections (from the
      anterior outer cortex to the posterior outer cortex) of 10 human lenses were
      imaged at 2 atmospheres (atm) pressure and the T(1) (spin-lattice) and T(2) (spin
      spin) relaxation data on each section were collected. The pressure was then
      released and NMR relaxographic data were collected under 1 atm. RESULTS: Both
      T(1) and T(2) relaxation times were at their minimum in the nuclear region and at
      their maximum at the two outer cortexes. With increasing pressure, T(2)
      relaxation times decreased. The pressure-dependent change in T(2) relaxation
      times decreased with age. Changes in T(1) relaxation times showed no consistent
      pressure or age dependence. The population index of T(2) relaxation, M(2), had a
      maximum in the nucleus and a minimum in the two cortexes. The population index of
      T(1) relaxation, M(1,) was minimal in the nucleus and maximal at the two
      cortexes. M(2) increased with increasing pressure, whereas M(1) did not show
      consistent pressure dependence. The percentage of change in M(2) (DeltaM(2))
      showed a statistically significant increase with increasing age, whereas the
      %DeltaM(1) showed no significant age-dependent trend. CONCLUSIONS: The positional
      dependence of relaxation times and the population indexes indicated that spin
      spin relaxation represents the behavior of the bound water and the spin-lattice
      relaxation that of total water. As pressure increases, the strength of hydrogen
      bonding as well as the amount of bound water increases. The pressure-induced
      change in the total water is minimal. Thus, the free water-to-bound water ratio
      decreases with increasing pressure, demonstrating a significant syneretic
      response. The extent of reversible syneretic response decreases with age and is
      actually reversed in older lenses. The implication is that the ability of the
      human lens to respond reversibly to pressure decreases with the decrease in
      accommodation, and, when the ability is lost altogether, an increase in free
      water, a possible source of cataract formation, may ensue.

PMID- 12506084
TI  - Effect of UVA light on the activity of several aged human lens enzymes.
AB  - PURPOSE: To determine the effect of UVA irradiation on the specific activities of
      several protective and metabolic enzymes in aged human lenses. METHODS: Intact
      human lenses (ages 55-75) in artificial aqueous humor were irradiated in a quartz
      cuvette with UVA light (925 J/cm(2) per hour) at +20 degrees C. The lenses were
      homogenized and the activities of enzymes in the water-soluble (WS) fraction were
      measured in irradiated and nonirradiated lenses. RESULTS: One hour of UVA
      photolysis of human lens resulted in a 70% loss in glutathione reductase (GR)
      specific activity and a 24% loss in glyceraldehyde-3-phosphate dehydrogenase
      (G3PD)-specific activity. At the same time, glutathione peroxidase (GPx) and
      superoxide dismutase (SOD) showed little or no loss in specific activity. GR and
      G3PD showed similar losses when human lenses were photolyzed with the same dose
      of UVA light delivered to the lens over 8 hours, using a 12.5% neutral-density
      filter (ndf), or over 24 hours with a 4.25% ndf. One hour photolysis of the human
      lens WS fraction under anaerobic conditions yielded an almost complete
      inactivation of GR, but only an 18% loss of G3PD activity. Under aerobic
      conditions, however, both enzyme activities were almost completely lost. Clear
      fetal bovine lenses, photolyzed under the identical conditions, displayed
      essentially the same loss of GR activity. CONCLUSIONS: UVA light causes
      inactivation of GR in human and fetal calf lenses under both anaerobic and
      aerobic conditions. This suggests that flavine adenine dinucleotide (FAD), the
      prosthetic group of GR, may be responsible for the enzyme's self-sensitizing
      properties. WS proteins from aged human lens generate reactive oxygen species
      (ROS) during UVA irradiation, which may be responsible for the inactivation of
      G3PD.

PMID- 12506085
TI  - Removal of reflections in the photographic assessment of PCO by fusion of digital
      retroillumination images.
AB  - PURPOSE: Automated image-analysis systems for objective assessment of posterior
      capsule opacification (PCO) depend on good image quality. One major drawback is
      the existence of light-reflection artifacts (Purkinje spots) in retroillumination
      images of the posterior capsule. Therefore, a software algorithm was developed
      that removes these artifacts by fusion of two or more digital images from the
      same eye, photographed in slightly different directions of gaze. METHODS: The
      image-fusion process comprises five steps: definition of a primary and a
      secondary image, automated segmentation of the region of interest and the
      Purkinje spots, manual selection of three pairs of corresponding points in both
      images, geometric registration and radiometric calibration of the regions to be
      inserted from the secondary image into the primary image. The program was tested
      with an image set of 30 eyes that had various degrees of PCO. A digital image
      acquisition system with a coaxial optical path was used to take retroillumination
      images from each eye in at least three different directions of gaze. RESULTS: In
      28 cases all light-reflection artifacts within the capsulorrhexis rim could be
      removed entirely. In two cases, small parts of single Purkinje spots remained
      visible, because the reflections were located too closely in the primary and the
      secondary images. CONCLUSIONS: Fusion of digital retroillumination images
      provides high-quality, reflection-free PCO images. This allows objective PCO
      assessment systems to analyze 100% of the posterior capsule, leading to more
      accurate results.

PMID- 12506086
TI  - Comparative study of the effects of 2% ibopamine, 10% phenylephrine, and 1%
      tropicamide on the anterior segment.
AB  - PURPOSE: To assess in normal and glaucomatous eyes the effect of the dopaminergic
      drug 2% ibopamine on visual acuity, IOP, pupil size and anterior segment
      geometry, compared with 10% phenylephrine and 1% tropicamide. METHODS: Fifteen
      healthy subjects and 15 patients with primary open-angle glaucoma, aged from 40
      to 70 years (mean age: 54.8 +/- 9.6), were recruited into this open prospective
      study. After instillation of 2% ibopamine, refraction, visual acuity, pupil
      diameter, IOP, five A-scan ultrasonographic parameters, and 15 ultrasound
      biomicroscopy parameters were evaluated. The study was repeated with assessment
      of the same parameters 20 to 30 days later in 10 subjects (5 normal and 5 with
      glaucoma), using first 10% phenylephrine and then 1% tropicamide. A second group
      of 15 healthy subjects, aged from 45 to 70 years (mean age: 53.5 +/- 8.6) was
      examined to evaluate the dose-response effect and time course on pupil diameter,
      of ibopamine, phenylephrine, and tropicamide. RESULTS: After 40 minutes 2%
      ibopamine induced a marked mydriatic effect (from 5 to 9.1 mm; P < 0.0001)
      greater than that produced by 10% phenylephrine (from 4.7 to 7.9 mm; P < 0.0001)
      or 1% tropicamide (from 4.6 to 6.9 mm; P < 0.0001), with no changes in refraction
      or visual acuity. IOP was significantly increased only in patients with glaucoma
      after instillation of either 2% ibopamine (from 22.2 to 24.8 mm Hg; P < 0.0001)
      or 1% tropicamide (from 21.2 to 23.6 mm Hg; P = 0.004), whereas 10% phenylephrine
      induced no statistically significant changes. Ibopamine (2%) caused a significant
      increase in iris thickness with a reduction of the sulcus ciliaris and posterior
      chamber depth. The anterior chamber angle (ACA) showed a mean 5 degrees widening
      with an increase in scleral-iris angle (SIA) and sclera-ciliary process angle. In
      11 (37%) of 30 cases, separation of the pupil border and lens surface occurred,
      whereas contact was maintained only with the zonule in the other 19 (63%) of 30.
      The changes after 10% phenylephrine instillation were similar, although only the
      increase in iris thickness and SIA was statistically significant. Tropicamide
      (1%) induced a slight but significant increase in SIA. CONCLUSIONS: The results
      confirm the potent mydriatic effect of 2% ibopamine, which is greater than that
      of either 10% phenylephrine or 1% tropicamide, as well as its ability to induce
      an increase in intraocular pressure when used in patients with glaucoma alone.
      These data support the hypothesis that the widening of the ACA induced by 2%
      ibopamine is due to posterior rotation of the iris plane and ciliary processes.
      These changes are quantitatively greater than those induced by 10% phenylephrine
      and 1% tropicamide and are related to the greater mydriatic effect of the drug.

PMID- 12506087
TI  - Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co
      glycolic)acid microspheres.
AB  - PURPOSE: To develop a controlled-drug delivery system for the long-term
      inhibition of vascular endothelial growth factor (VEGF) and its mediated
      responses. METHODS: Poly(lactic-co-glycolic)acid (PLGA) microspheres containing
      anti-VEGF RNA aptamer (EYE001) formulations in the solid-state were developed by
      an oil-in-oil solvent evaporation process. In vitro experiments were performed to
      characterize the release profiles. Stability and bioactivity of the released drug
      were assayed by monitoring the RNA aptamer's ability to inhibit VEGF-induced cell
      proliferation in human umbilical vein endothelial cells (HUVECs). Cell
      proliferation experiments were conducted with aptamer aliquots collected after
      short-, mid-, and long-term release time points. To investigate the feasibility
      of this polymer device as a potential transscleral delivery device, an in vitro
      apparatus was developed to assess polymer hydration and degradation through
      rabbit sclera and subsequent delivery through it. RESULTS: PLGA microspheres were
      able to deliver EYE001 in a sustained manner, with an average rate of 2 micro g/d
      over a period of 20 days. Solid-state stabilization of the aptamer with
      disaccharide trehalose before lyophilization and encapsulation in PLGA rendered
      the drug more stable after release. Cell proliferation experiments demonstrated
      that the bioactivity of the aptamer was preserved after release, as indicated by
      inhibition of endothelial cell proliferation after incubation with VEGF.
      Microspheres packed into a sealed chamber and placed onto the "orbital" part of a
      rabbit sclera for a period of 6 days became hydrated and started to degrade, as
      shown by scanning electron microscopy (SEM). As a result, the aptamer was
      delivered from the microspheres through the sclera, as determined
      spectrophotometrically. CONCLUSIONS: The loading of aptamer-containing
      microspheres into a device and placing it on the orbital surface of the sclera
      was assessed and shown to be feasible. RNA aptamer EYE001 encapsulated in PLGA
      was delivered over a period of 20 days with retained activity. This method
      represents a promising approach for the transscleral delivery of drugs and the
      treatment of choroidal and retinal diseases.

PMID- 12506088
TI  - Posterior segment ocular pharmacokinetics using microdialysis in a conscious
      rabbit model.
AB  - PURPOSE: To develop and establish a conscious rabbit model for ocular
      pharmacokinetic studies and to delineate the effects of anesthesia and probe
      implantation on the ocular disposition of ganciclovir. METHODS: A conscious
      rabbit model was developed for microdialysis of the posterior ocular segment.
      Rabbits were divided into three groups. Group I consisted of rabbits with no
      recovery period after probe implantation and were anesthetized throughout the
      experiment. Group II consisted of rabbits that had a more than 5-day recovery
      period and were conscious during the experiment. Group III consisted of rabbits
      that had a more than 5-day recovery period and were anesthetized during the
      experiment. (3)[H] ganciclovir was administered (50 microL) intravitreously in
      all groups, and ocular levels were determined for 10 hours at appropriate time
      intervals. Data obtained were subjected to noncompartmental modeling. RESULTS:
      Probe calibration studies indicated that the probes were functional for at least
      14 days. The anesthetized groups, regardless of the period of recovery from probe
      implantation, exhibited higher areas under the curve than did the conscious
      group. The vitreous half-life of ganciclovir was significantly shorter in the
      groups with a recovery period of more than 5 days compared with the group with no
      recovery period. CONCLUSIONS: The conscious rabbit model was developed and can be
      used for a period of at least 14 days. Anesthesia increased ocular
      bioavailability of intravitreously administered ganciclovir, whereas probe
      implantation led to increased protein efflux into the vitreous, which may be the
      reason for the increased half-life of ganciclovir in group I.

PMID- 12506089
TI  - Light exposure and macular pigment optical density.
AB  - PURPOSE: Biochemical research has demonstrated that lutein and zeaxanthin, the
      two macular carotenoids, are bleachable pigments. Further, evidence suggests that
      exposure to UV light can degrade plasma carotenoid levels in vivo. The present
      study investigated the effects of exposure to normal levels of light on the
      levels of lutein and zeaxanthin in the retina. METHODS: The optical density of
      macular pigment (MPOD) was measured in two male subjects under four different
      light-adaptation conditions for 20 days. Heterochromatic flicker photometry was
      used to measure MPOD at 0.5 degrees eccentricity. RESULTS: The four conditions of
      light adaptation did not significantly affect MPOD. As in previous studies,
      however, a significant day-to-day difference was observed for both subjects.
      CONCLUSIONS: The results suggest that lutein and zeaxanthin levels in the eye are
      unaffected by light and oxidation throughout the day. This justifies current
      research methods in which MPOD measures are made regardless of the time of day.
      However, significant between-day variance indicates that multiple MPOD measures
      may be necessary to evaluate lutein and zeaxanthin levels in the retina
      accurately.

PMID- 12506090
TI  - Correlation of regenerable opsin with rod ERG signal in Rpe65-/- mice during
      development and aging.
AB  - PURPOSE: RPE65 has been shown to be essential for the production of 11-cis
      retinal by the retinal pigment epithelium. Mutations in RPE65 are known to be
      associated with severe forms of early-onset retinal dystrophy. This project was
      designed to determine the amount of regenerable opsin in Rpe65-/- mice during
      development and aging, and to examine the function of this rhodopsin by
      electroretinography (ERG). METHODS: Young and aged Rpe65-/- and wild-type (WT)
      mice were dark adapted. Endogenous rhodopsin and regenerable opsin were measured
      using absorption-difference spectrophotometry. Photoreceptor function was
      assessed with scotopic single-flash ERGs and photoreceptors were counted in
      histologic sections. Opsin's primary structure was analyzed by mass-spectrometric
      mapping. RESULTS: Unlike WT mice, amounts of regenerable opsin in Rpe65-/- mice
      decreased significantly with age, which correlated with a decrease in the number
      of photoreceptors and a decline in ERG amplitudes. Opsin structure, however, did
      not change. No endogenous levels of rhodopsin were measurable in the Rpe65-/-
      mice (detection limit: 0.225 pmol). 11-cis Retinal injections resulted in the
      regeneration of similar amounts of rhodopsin and improved rod function in a
      comparable way, irrespective of age. CONCLUSIONS: In the aged Rpe65-/- mouse,
      opsin levels decrease because of the loss of photoreceptors. The remaining opsin
      is structurally intact, and the components of the phototransduction cascade and
      the retinal circuitry remain functional, despite the absence of normal
      photoreceptor activity.

PMID- 12506091
TI  - Retinal damage from indocyanine green in experimental macular surgery.
AB  - PURPOSE: Previous work has shown that indocyanine green (ICG)-assisted peeling of
      the inner limiting membrane (ILM) may cause retinal damage. In this study, a
      toxic and a photodynamic effect of ICG at the vitreoretinal interface was
      assumed. METHODS: Ten human donor eyes were hemisected, and 0.05 mL of 0.05% ICG
      was poured over the trephined macula in eight eyes. After 1 minute, the dye was
      drained by irrigation. The macula in each of two eyes was illuminated for 3
      minutes with wavelengths of 380 to 760, 380 to 620, or 620 to 760 nm. Two eyes
      were treated with ICG only, and two eyes were illuminated only. Retinal specimens
      from the macula and the untreated retina were processed for light and electron
      microscopy. The irradiance of the light source and the absorption properties of
      ICG were measured. RESULTS: Exposure of the ICG-stained ILM to wavelengths beyond
      620 nm resulted in severe damage to the inner retina, including loss of ILM,
      cellular disorganization, and fragmentation of the cytoplasm. ICG staining alone
      or in combination with wavelengths of 380 to 620 nm disclosed rupture of Muller
      cells with detachment of the ILM, but no other cellular disorganization. Eyes
      subjected to illumination only showed no abnormalities. CONCLUSIONS: The spectral
      absorption properties of ICG may account for a possible photodynamic effect of
      ICG at the vitreoretinal interface. ICG alone induces ILM detachment and
      disruption of Muller cells even without intentional peeling of the membrane. It
      is assumed that accumulation of the dye at the vitreomacular interface may
      enhance the concentration and osmolarity of ICG at the retina beyond
      intravitreous values and critical limits.

PMID- 12506092
TI  - Limitation of anatomical integration between subretinal transplants and the host
      retina.
AB  - PURPOSE: In previous studies of subretinal transplantation in rabbits, the host
      photoreceptor layer seemed to prevent the bridging of neuronal fibers between the
      graft and the host retina. The current study was undertaken to determine whether
      the same phenomenon occurs in transplants to the subretinal space of the
      vascularized retina of rats. Bridging of fibers was examined in transplants to
      animals of different genetic backgrounds (normal versus dystrophic rats), of
      different ages, and after different survival times. METHODS: Sprague-Dawley (SD)
      rat retinal tissue from embryonic day (E)18 was subretinally grafted to adult (60
      day-old) normal SD rats, to RCS rats (32 and 73 days old), and to adult (60-day
      old) transgenic P23H rats. After various survival times (28-183 days),
      transplanted retinas were processed for routine histology and
      immunocytochemistry. Antibodies against calbindin, neuronal nitric oxide synthase
      (NOS), and protein kinase C (PKC) were used to identify specific retinal cell
      types and their processes. RESULTS: The shape and position of the immunoreactive
      cell bodies indicated that the expected neuronal populations were labeled within
      the grafts and in the host retina. Labeled neuronal processes were also observed.
      In each case, NOS-, calbindin-, and PKC-immunolabeled fibers formed bridges
      between the graft and the host tissues. However, regardless of the extent of host
      photoreceptor cell loss, the age of the recipient, or the genetic background,
      bridging fibers were observed only in areas where the host photoreceptor layer
      was discontinuous or completely missing. CONCLUSIONS: The present study
      demonstrates that the host photoreceptor layer plays a role in limiting graft
      host anatomical integration.

PMID- 12506093
TI  - Inhibitory effects of antithrombin III on interactions between blood cells and
      endothelial cells during retinal ischemia-reperfusion injury.
AB  - PURPOSE: Infiltrating leukocytes have long been widely thought to be key
      mediators of ischemia-reperfusion injury. Recently, however, evidence suggests
      that platelets accumulating in postischemic tissues also contribute to ischemia
      reperfusion injury because of their inflammatory properties and promotion of
      formation of thrombi. This study was designed to evaluate quantitatively the
      inhibitory effects of antithrombin (AT)-III on the interactions between blood
      cells and retinal endothelial cells in vivo after transient retinal ischemia.
      METHODS: Transient retinal ischemia was induced for 60 minutes in male Long-Evans
      rats by ligation of the optic nerve. AT III (250 U/kg) was administered
      intravenously just after induction of ischemia. Leukocyte and platelet behavior
      in the retina was evaluated in vivo with a scanning laser ophthalmoscope.
      Expression of P-selectin and intracellular adhesion molecule (ICAM)-1 in the
      postischemic retina was investigated by reverse transcription-polymerase chain
      reaction and immunohistochemistry. After 14 days of reperfusion, ischemia-induced
      retinal damage was evaluated histologically. RESULTS: Administration of AT III
      significantly inhibited leukocyte rolling along the major retinal veins and
      subsequent accumulation of leukocytes in the postischemic retina. Furthermore,
      the maximum number of rolling and adherent platelets was reduced by 76% (P <
      0.01) and 48% (P < 0.01), respectively, at 12 hours after reperfusion.
      Immunohistochemical studies also revealed the suppressive effect of AT III on
      expression of P-selectin and ICAM-1. Finally, histologic examination demonstrated
      the protective effects of AT III against retinal damage after transient retinal
      ischemia. CONCLUSIONS: This study demonstrates the inhibitory effects of AT III
      on leukocyte and platelet recruitment to the postischemic retina, which may
      account for the neuroprotective properties of this alpha-2 globulin against
      retinal ischemia-reperfusion injury.

PMID- 12506094
TI  - Prion protein accumulation in eyes of patients with sporadic and variant
      Creutzfeldt-Jakob disease.
AB  - PURPOSE: Creutzfeldt-Jakob disease (CJD) primarily affects the brain. This study
      was conducted to assess the possible involvement of the eye in sporadic and
      variant CJD by testing for the presence of the disease-associated, protease
      resistant isoform of the prion protein (PrP(Sc)) in ocular tissue. METHODS: Human
      eyes from donors with CJD and non-prion neurodegenerative disease control eyes
      were studied. In situ hybridization and Western blot analysis were used to
      determine the normal pattern of cellular prion protein (PrP(C)) expression.
      Western blot analysis and immunohistochemistry were then used to determine the
      localization, abundance, and isotype of PrP(Sc) in eyes in CJD. RESULTS: PrP(C)
      was expressed in the nuclear layers of the retina. In both the sporadic and
      variant forms of CJD, PrP(Sc) accumulated throughout the synaptic layers of the
      retina. The levels of PrP(Sc) found in the retina were comparable with those
      found in the brain. Lower levels of PrP(Sc) could be found in the optic nerve,
      but no PrP(Sc) was detectable in other ocular tissues. The glycoform ratio of
      PrP(Sc) in the retina did not correspond to that found in the brain. CONCLUSIONS:
      Presumptive centrifugal spread of PrP(Sc) from the brain through the optic nerve
      occurs in two major types of CJD. PrP(Sc) is a marker of CJD infectivity. Given
      that routine decontamination may not remove PrP(Sc) from surgical instruments, a
      careful risk assessment should be made of possible iatrogenic spread of sporadic
      and variant CJD after surgery to the retina or optic nerve.

PMID- 12506095
TI  - Support of retinal ganglion cell survival and axon regeneration by lithium
      through a Bcl-2-dependent mechanism.
AB  - PURPOSE: To explore whether lithium, a long-standing mood-stabilizing drug, can
      be used to induce expression of Bcl-2 and support the survival and regeneration
      of axons of retinal ganglion cells (RGCs). METHODS: Levels of expression of Bcl-2
      in the retina were assessed with quantitative reverse transcription-polymerase
      chain reaction. To determine whether lithium directly supports the survival of
      and axon-regenerative functions of RGCs, various amounts of lithium were added to
      cultures of isolated RGCs. Anti-Thy1.2 antibodies-conjugated to magnetic beads
      were used to isolate the RGCs. In addition, retina-brain slice cocultures were
      prepared from tissues of Bcl-2-deficient or Bcl-2-transgenic mice and treated
      with various amounts of lithium. The effects of the expression of Bcl-2 on
      lithium-mediated functions were then analyzed. RESULTS: Normal mouse retina
      expressed very low levels of Bcl-2 after birth. Addition of lithium in the
      culture increased mRNA levels of Bcl-2 in retinas of postnatal mice in a dose
      dependent manner. Moreover, lithium promoted not only the survival of RGCs but
      also the regeneration of their axons. Depleting or forcing the expression of Bcl
      2 in RGCs eliminated the effects of lithium. CONCLUSIONS: Lithium supports both
      the survival and regeneration of RGC axons through a Bcl-2-dependent mechanism.
      This suggests that lithium may be used to treat glaucoma, optic nerve neuritis,
      the degeneration of RGCs and their nerve fibers, and other brain and spinal cord
      disorders involving nerve damage and neuronal cell loss. To achieve full
      regeneration of the severed optic nerve, it may be essential to combine lithium
      therapy with other drugs that mediate induction of a permissive environment in
      the mature central nervous system.

PMID- 12506096
TI  - Tissue transglutaminase as a modifying enzyme of the extracellular matrix in PVR
      membranes.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is characterized by the
      development of epi- and subretinal fibrocellular membranes containing modified
      retinal pigment epithelial (RPE) cells among others. In the present study, the
      role of transglutaminases in accumulation of extracellular matrix (ECM) proteins
      in these membranes was investigated. Transglutaminases are enzymes capable of
      cross-linking ECM proteins to proteolysis-resistant complexes. METHODS: PVR
      membranes were incubated with dansyl-cadaverine to demonstrate active
      transglutaminase. Localization of tissue transglutaminase (tTgase), its reaction
      product epsilon-(gamma-glutamyl)-lysine, and fibronectin was investigated
      immunohistochemically. Colocalization was studied with a confocal laser scanning
      microscope. PVR membranes were also analyzed by RT-PCR for the presence of tTgase
      mRNA. In vitro, RPE cells were treated with transforming growth factor-beta2 (TGF
      beta2), basic fibroblast growth factor, interleukin-6, and interleukin-1beta.
      Their effect was studied using immunohistochemistry and Northern and Western blot
      analyses. RESULTS: Transglutaminase activity and expression of tTgase were
      present in all PVR membranes. Staining was most prominent at the rim of the
      membranes. The enzyme was colocalized with epsilon-(gamma-glutamyl)-lysine and
      fibronectin. No staining differences were found between epi- and subretinal
      membranes. Although native RPE cells contained only a basal level of tTgase mRNA,
      the expression and activity of tTgase was increased under culture conditions and
      further stimulated by TGF-beta2 treatment. CONCLUSIONS: The findings demonstrate
      that in PVR membranes tTgase is present and functionally active. The amount and
      activity of this enzyme appears to be related to the differentiation state of the
      RPE cells and their stimulation by TGF-beta2, a growth factor known to be
      increased in the vitreous of PVR. Intervention at this pathway may open a new
      approach for PVR prevention and therapy.

PMID- 12506097
TI  - Expression of IGFBP-3 by human retinal endothelial cell cultures: IGFBP-3
      involvement in growth inhibition and apoptosis.
AB  - PURPOSE: Growth hormone (GH), insulin-like growth factor (IGF), and somatostatin
      (SST) modulate each other's actions. SST analogues have been successfully used to
      treat proliferative diabetic retinopathy (PDR) that is unresponsive to laser
      therapy and to retard the progression of severe nonproliferative retinopathy to
      PDR. In this study, the endogenous expression of IGF-binding protein (IGFBP)-3
      was examined in human retinal endothelial cells (HRECs), the direct effects of
      IGFBP-3 on HRECs were evaluated, and the possible involvement of IGFBP-3 in
      mediating the growth inhibitory effects of SST receptor (SSTR) agonists in HRECs
      was assessed. METHODS: The cellular localization of IGFBP-3 was examined with
      anti-IGFBP-3 and fluorescein-conjugated goat anti-rabbit IgG. HRECs were exposed
      to varying concentrations of human recombinant IGFBP-3, and growth inhibition was
      evaluated by thiazolyl blue (MTT) conversion. Apoptosis was examined using
      fluorochrome-annexin V staining. Conditioned media (CM) from SSTR2 agonist
      (L779976)-treated or SSTR3 agonist (L796778)-treated HRECs were analyzed by ELISA
      for changes in expression of IGFBP-3. RESULTS: HREC immunostaining showed cell
      surface and cytoplasmic IGFBP-3. Exogenous IGFBP-3 induced a dose-dependent
      inhibition of HREC proliferation and staining with fluorochrome-annexin V showed
      numerous apoptotic HRECs. HRECs exposed to the SSTR2 or SSTR3 agonists expressed
      IGFBP-3 in a concentration-dependent manner. CONCLUSIONS: Cultured HRECs
      expressed endogenous IGFBP-3. Exogenous administration of IGFBP-3-induced growth
      inhibition and apoptosis, supporting a regulatory role for IGFBP-3 in endothelial
      cells. SSTR agonists mediate their growth-inhibitory effect, in part, by
      increasing expression of IGFBP-3.

PMID- 12506098
TI  - Effect of indocyanine green and illumination on gene expression in human retinal
      pigment epithelial cells.
AB  - PURPOSE: To investigate the biological effects of indocyanine green (ICG) and
      acute illumination on human retinal pigment epithelial (RPE) cells. METHODS:
      Three concentrations (0, 0.25, and 2.5 mg/mL) of ICG were applied to ARPE19 cells
      for 1 minute. After isotonic rinsing, the cells were irradiated with a light beam
      with a wavelength spectrum from 400 to 800 nm and an output of 1850 lumens for 15
      minutes. The cells were collected at timed intervals for the investigation of
      cell death and expression of stress-response genes by reverse transcription
      polymerase chain reaction, immunofluorescence, and Western blot analysis.
      RESULTS: After ICG incubation, photoreactive changes were observed in the RPE
      cells. A reduction in cellular viability and considerable shrinkage of the cells
      were observed. The expressions of the apoptosis-related genes p53 and bax and the
      cell cycle arrest protein p21 were upregulated in cells treated with both ICG and
      light. Of the early-response genes, the expression of c-fos was specifically
      enhanced by light, with additive effects from the presence of ICG. Such
      stimulatory effects on these gene expressions were greater at 2.5 mg/mL than at
      0.25 mg/mL ICG. CONCLUSIONS: ICG in the presence of acute illumination can elicit
      cell-cycle arrest and even apoptosis in RPE cells. The establishment of a safety
      level in the application of ICG in the region of 0.25 mg/mL is recommended.

PMID- 12506099
TI  - Identification of the gene and the mutation responsible for the mouse nob
      phenotype.
AB  - PURPOSE: The available evidence indicates that the naturally occurring mouse
      mutant nob (no b-wave) provides an animal model for the complete form of human X
      linked congenital stationary night blindness (CSNB1). The goals of the present
      study were to identify the nob gene defect, to characterize the expression
      pattern of the involved gene, and to assess visual sensitivity in nob mice.
      METHODS: Positional cloning, screening of candidate genes, and sequencing were
      used to identify the nob gene. The expression pattern of the nyx gene was
      examined with Northern blot analysis and in situ hybridization. Visual
      sensitivity was measured with an active avoidance behavioral test. RESULTS: The
      nob phenotype is caused by an 85-bp deletion in the mouse nyx gene, which encodes
      the nyctalopin protein. Expression of nyx was most abundant in the retina and, in
      particular, in the inner nuclear layer. The nyctalopin protein contains 11
      leucine-rich repeats and is flanked by cysteine rich regions, which identifies it
      as a member of the small leucine rich proteoglycan family. Behavioral testing
      shows that nob mice have a significant decrease in visual sensitivity.
      CONCLUSIONS: The nob mouse is a model for human CSNB1. This model will be useful
      in defining the role of nyctalopin in signal transmission between photoreceptors
      and retinal bipolar cells.

PMID- 12506100
TI  - Divergent NMDA signals leading to proapoptotic and antiapoptotic pathways in the
      rat retina.
AB  - PURPOSE: To investigate the involvement of the p38 mitogen-activated protein
      (MAP) kinase and phosphatidylinositol-3 (PI-3) kinase-Akt signaling pathways
      after pathologic stimulation by N-methyl-D-aspartate (NMDA) receptors of retinal
      neurons in vivo. METHODS: NMDA (2-200 nmol), SB203580 (0.2-10 nmol, an inhibitor
      of p38 MAP kinase), LY294002 (6 nmol, an inhibitor of PI-3 kinase), or control
      solution was injected into the vitreous of Long-Evans rats. To assess retinal
      ganglion cell (RGC) death quantitatively, we labeled RGCs retrogradely by
      injecting aminostilbamidine (FluoroGold) into the superior colliculus and
      subsequently counting fluorescently labeled RGCs in retinal wholemounts.
      Phosphorylation of p38 and Akt was assessed by immunoblot of whole retinal
      lysates, and activity was measured with in vitro kinase assays. To localize
      phospho-p38 and phospho-Akt, immunohistochemistry was performed. TUNEL staining
      coupled with morphologic assessment was performed to assess apoptotic cell death.
      RESULTS: Intravitreous injection of more than 10 nmol NMDA induced RGC death.
      Before death, NMDA-stimulated retinas manifested increased phospho-p38 and
      phospho-Akt in the ganglion cell and inner nuclear layers. Subsequently,
      pyknotic, TUNEL-positive cells were also localized to these regions. SB203580
      partially rescued RGCs, whereas LY294002 enhanced death of RGCs due to 10 nmol
      NMDA. SB203580 and LY294002 specifically inhibited the activity of p38 MAP kinase
      and Akt, respectively. CONCLUSIONS: The p38 MAP kinase and PI-3 kinase-Akt
      pathways are involved in signal transduction after excessive stimulation of NMDA
      receptors in the retina. These inhibitor studies suggest that the p38 MAP kinase
      pathway is proapoptotic, whereas the PI-3 kinase-Akt pathway is antiapoptotic in
      RGC death induced by NMDA.

PMID- 12506101
TI  - Potential role of the angiopoietin/tie2 system in ischemia-induced retinal
      neovascularization.
AB  - PURPOSE: Ischemia-induced neovascularization can cause catastrophic loss of
      vision in retinal disorders such as diabetic retinopathy. Recent studies have
      shown that the angiopoietin-Tie2 system is a major regulator of vascular
      integrity and is involved in pathologic angiogenesis. In the study described
      herein, the role of these molecules in ischemic retinal disorders was
      investigated. METHODS: Human epiretinal membranes were examined by
      immunohistochemistry, In situ hybridization, and reverse transcription-polymerase
      chain reaction (RT-PCR) analysis. Effects of angiopoietins on tube formation were
      studied in vitro in bovine retinal capillary endothelial cells (BRECs) and in a
      murine model of ischemia-induced retinal neovascularization. RESULTS: In human
      epiretinal membranes surgically obtained from eyes with ischemic retinal
      disorders, substantial upregulation of angiopoietin 2 (Ang2) and the receptor
      Tie2 was recorded than in those from eyes with nonischemic diseases, whereas
      expression of Ang1 was constant in all membranes. Both Ang1 and Ang2 promoted
      tube-forming activity and enhanced the effects of vascular endothelial growth
      factor (VEGF) in cultured BRECs. Soluble Tie2 fusion protein (sTie2-Fc), which
      precluded modulation of VEGF-dependent tube formation by the angiopoietins,
      suppressed both VEGF and hypoxia-conditioned, medium-induced tube-forming
      activity in BRECs. Intravitreal injection of sTie2-Fc, soluble Flt-1 fusion
      protein (sFlt-1-Fc), and both chimeric proteins suppressed retinal angiogenesis
      in a murine model of retinal ischemia in the order of sTie2-Fc < sFlt-1-Fc <
      sTie2-Fc+sFlt-1-Fc. CONCLUSIONS: These results reinforce the substantial role of
      the angiopoietins/Tie2 system in ischemia-induced angiogenesis as well as the
      VEGF system and suggest that combined inhibition of Tie2 and VEGF signaling may
      be more effective in halting or preventing pathologic angiogenesis in ischemic
      retinal disorders.

PMID- 12506102
TI  - Reduced choroidal neovascular membrane formation in matrix metalloproteinase-2
      deficient mice.
AB  - PURPOSE: Findings in studies have suggested a role for matrix metalloproteinase
      (MMP)-2 in angiogenesis, including choroidal neovascularization (CNV). To
      investigate further, the current study was conducted to observe the formation of
      experimental CNV in MMP-2-deficient mice. METHODS: CNV was induced in wild-type
      and MMP-2-deficient mice by krypton laser photocoagulation of the fundus. The
      time-course of expression of MMP-2 mRNA after laser treatment was determined by
      in situ hybridization with anti-sense and sense cRNA probes. MMP-2 protein
      distribution was determined by immunohistochemistry. Ten days after treatment,
      the extent of CNV was evaluated on hematoxylin-eosin stained serial sections. The
      maximum height of the CNV lesions was calculated by image analysis of digitized
      histologic images. RESULTS: Expression of MMP-2 mRNA was detected in the CNV
      lesions at day 3 after laser treatment and peaked at day 5, after which it slowly
      declined. MMP-2 mRNA expression appeared to be highest at the margins of the
      membrane. Immunostaining for MMP-2 confirmed the presence of MMP-2 protein in the
      CNV lesions. The CNV lesions of MMP-2-deficient mice showed that relative
      thickness was reduced by 31% compared with wild-type mice (P = 0.006).
      CONCLUSIONS: The present study demonstrated that MMP-2 mRNA and protein are
      upregulated during experimental CNV in the mouse. The marked difference in
      thickness of the CNV membrane between wild-type and MMP-2-deficient mice shows
      that MMP-2 is involved in the formation of experimental CNV in the mouse. These
      results suggest that pharmacologic targeting of MMPs, including MMP-2, may reduce
      formation of CNV in conditions such as age-related macular degeneration.

PMID- 12506103
TI  - Topical nepafenac inhibits ocular neovascularization.
AB  - PURPOSE: Topical nepafenac readily penetrates the cornea and is metabolized to
      amfenac, a potent cyclooxygenase (COX)-1 and COX-2 inhibitor. In this study, we
      tested the effect of topical nepafenac in three murine models of ocular
      neovascularization (NV). METHODS: A masked trial was performed to compare the
      topical effects of vehicle with one of several concentrations of nepafenac
      (0.01%, 0.03%, 0.1%, or 0.5%), 0.1% diclofenac, or 0.5% ketorolac tromethamine in
      mice with oxygen-induced ischemic retinopathy, mice with choroidal NV (CNV) due
      to laser-induced rupture of Bruch's membrane, or transgenic mice with increased
      expression of vascular endothelial growth factor (VEGF) in photoreceptors
      (rho/VEGF transgenic mice). RESULTS: Mice treated with 0.1% or 0.5% nepafenac had
      significantly less CNV and significant less ischemia-induced retinal NV than did
      vehicle-treated mice. Nepafenac also blunted the increase in VEGF mRNA in the
      retina induced by ischemia. In rho/VEGF transgenic mice, nepafenac failed to
      inhibit neovascularization. In additional studies, compared with vehicle-treated
      mice, mice treated with 0.1% or 0.03% nepafenac had significantly less CNV,
      whereas eyes treated with 0.1% diclofenac showed no significant difference. Mice
      treated with 0.5% ketorolac tromethamine for 14 days had high mortality, but when
      evaluated after 7 days of treatment showed no difference from mice treated with
      vehicle for 7 days. CONCLUSIONS: Topical nepafenac inhibits CNV and ischemia
      induced retinal neovascularization by decreasing production of VEGF. The absence
      of effect in rho/VEGF transgenic mice is consistent with this mechanism. Topical
      nepafenac may provide an effective new treatment for ocular neovascularization.
      The excellent corneal penetration of nepafenac certainly plays an important role
      in this effect. It is possible that other antiangiogenic agents are also amenable
      to topical application after formulations are identified that maximize their
      corneal penetration. Because of the many advantages of the topical route of
      delivery, this is a possible topic for exploration.

PMID- 12506104
TI  - Cone photoreceptor recovery after experimental detachment and reattachment: an
      immunocytochemical, morphological, and electrophysiological study.
AB  - PURPOSE: To compare the morphologic and functional recovery of the retina after
      detachment and reattachment in an animal with a cone-dominant retina, the ground
      squirrel. METHODS: Ground squirrel (Spermophilus beecheyi) retinas were detached
      for 1 day and reattached for 7, 35, or 96 days (n = 2, each time point). Flicker
      ERGs were recorded 1 day after the detachment and at various times after
      reattachment. Contrast-response functions were measured for isochromatic
      modulation and for selective modulation of short-wavelength-sensitive (S) and
      middle-wavelength-sensitive (M) cones. At the end of the experiment, retinas were
      prepared for light microscopy or immunocytochemical staining with antibodies to
      rod opsin, S and M cone opsins, cytochrome oxidase, synaptophysin, glial
      fibrillary acidic protein (GFAP), cellular retinaldehyde-binding protein
      (CRALBP), interphotoreceptor-binding protein (IRBP), and peanut agglutinin lectin
      (PNA). Photoreceptor density maps were created from wholemount preparations
      labeled with biotinylated PNA and anti-S cone opsin. Cell counts of photoreceptor
      nuclei and cone outer segments (OS) were compared with flicker ERG data. Cell
      death was examined by the TUNEL method. RESULTS: Reattachment stopped
      photoreceptor cell death and reversed the disruption of interphotoreceptor matrix
      as well as the redistribution of Muller cell proteins. It also activated some
      astrocytes based on anti-GFAP staining. S- and M-cone OS showed a gradual
      recovery in length after reattachment, and this recovery continued to the longest
      time points examined. ERG contrast gains also recovered after reattachment, but
      these reached asymptotic levels by approximately a week after reattachment. There
      were significant correlations between outer nuclear layer (ONL) cell counts and
      ERG contrast gains. No differences were noted in the indices of recovery of M and
      S cones. CONCLUSIONS: The ERG can be used to follow specifically the changes in
      the retina that occur after retinal detachment and reattachment.

PMID- 12506105
TI  - Incorporation of murine brain progenitor cells into the developing mammalian
      retina.
AB  - PURPOSE: To investigate the influence of a developing host environment on the
      survival, differentiation, and morphologic integration of murine brain progenitor
      cells (mBPCs) transplanted into the mammalian retina. METHODS: Enhanced green
      fluorescent protein (GFP)-expressing murine brain progenitor cells were
      transplanted into developing and mature Brazilian opossums (Monodelphis
      domestica). Animals were allowed to survive for up to 4 weeks after
      transplantation, at which time the eyes were prepared for immunohistochemical
      analysis. RESULTS: Transplanted mBPCs survived and differentiated in vivo, and
      extensive morphologic integration was observed within the host retinas. GFP
      expressing cells often displayed morphologies characteristic of retinal neurons.
      GFP somata were located in nuclear layers, and their processes ramified
      throughout the inner (IPL) and outer (OPL) plexiform layers. Furthermore, in some
      cases, GFP-expressing neurites were confined to specific sublamina within the
      IPL. The greatest morphologic integration and differentiation were observed after
      transplantation into the youngest-aged host eyes. Some transplanted mBPCs
      incorporated within the inner retina expressed the neuronal markers microtubule
      associated protein (MAP)-2 or calretinin. Transplanted cells coexpressed GFP and
      recoverin only in the ONL. CONCLUSIONS: mBPCs survived and morphologically
      integrated after xenotransplantation without immunosuppression. mBPCs were
      capable of incorporating into specific layers of the retina and expressing
      neuronal and retinal markers. The age of the host appeared to play a key role in
      determining cell fate in vivo.

PMID- 12506106
TI  - Selective loss of orientation column maps in visual cortex during brief elevation
      of intraocular pressure.
AB  - PURPOSE: To compare the orientation column maps elicited by different spatial
      frequency gratings in cortical area 17 of cats before and during brief elevation
      of intraocular pressure (IOP). METHODS: IOP was elevated by injecting saline into
      the anterior chamber of a cat's eye through a syringe needle. The IOP was
      elevated enough to cause a retinal perfusion pressure (arterial pressure minus
      IOP) of approximately 30 mm Hg during a brief elevation of IOP. The visual
      stimulus gratings were varied in spatial frequency, whereas other parameters were
      kept constant. The orientation column maps of the cortical area 17 were
      monocularly elicited by drifting gratings of different spatial frequencies and
      revealed by a brain intrinsic signal optical imaging system. These maps were
      compared before and during short-term elevation of IOP. RESULTS: The response
      amplitude of the orientation maps in area 17 decreased during a brief elevation
      of IOP. This decrease was dependent on the retinal perfusion pressure but not on
      the absolute IOP. The location of the most visible maps was spatial-frequency
      dependent. The blurring or loss of the pattern of the orientation maps was most
      severe when high-spatial-frequency gratings were used and appeared most
      significantly on the posterior part of the exposed cortex while IOP was elevated.
      However, the basic patterns of the maps remained unchanged. Changes in cortical
      signal were not due to changes in the optics of the eye with elevation of IOP.
      CONCLUSIONS: A stable normal IOP is essential for maintaining normal visual
      cortical functions. During a brief and high elevation of IOP, the cortical
      processing of high-spatial-frequency visual information was diminished because of
      a selectively functional decline of the retinogeniculocortical X pathway by a
      mechanism of retinal circulation origin.

PMID- 12506107
TI  - Contrast-processing dysfunction in both magnocellular and parvocellular pathways
      in migraineurs with or without aura.
AB  - PURPOSE: To assess contrast-discrimination thresholds in patients with migraine
      who have manifest visual field loss. This study was undertaken to determine
      whether contrast processing abnormalities in migraineurs are more readily
      identified by using stimuli that elicit a response from the subject that depends,
      at least in part, on adaptation mechanisms, and if so, whether deficits appear
      more pronounced in magnocellular (M) or parvocellular (P) visual pathways.
      METHODS: Ten patients with migraine who had abnormal visual fields measured with
      flicker perimetry but had normal standard automated perimetry (SAP) thresholds
      participated, along with 15 age-matched control subjects. Contrast-discrimination
      performance was assessed with the steady-pedestal (magnocellular) and pulsed
      pedestal (parvocellular) stimuli of Pokorny and Smith for seven pedestal
      luminances between 15 and 60 cd/m(2) on a background of 30 cd/m(2). Subjects were
      tested foveally and midperipherally at 12.5 degrees. Migraineurs were tested in
      the quadrant of worst visual field performance. Control subjects were assessed in
      locations matched to those of the migraine group. RESULTS: Foveal performance was
      not significantly different between the migraine and control groups for either
      task. At 12.5 degrees the migraine group had significantly raised thresholds for
      both conditions. Effect size statistics revealed similar deficit magnitudes for
      each test (steady pedestal, -1.06; pulsed pedestal, -1.04). CONCLUSIONS:
      Dysfunction in both the M and P pathways was identified in the midperipheral
      visual field of the migraine group. The P pathway dysfunction was not identified
      by SAP. These findings support the possibility of nonselective neural adaptation
      abnormalities in some subjects with migraine.

PMID- 12506108
TI  - Analysis of heme structural heterogeneity in Mycobacterium tuberculosis catalase
      peroxidase (KatG).
AB  - Mycobacterium tuberculosis catalase-peroxidase (KatG) is a heme enzyme considered
      important for virulence, which is also responsible for activation of the anti
      tuberculosis pro-drug isoniazid. Here, we present an analysis of heterogeneity in
      KatG heme structure using optical, resonance Raman, and EPR spectroscopy.
      Examination of ferric KatG under a variety of conditions, including enzyme in the
      presence of fluoride, chloride, or isoniazid, and at different stages during
      purification in different buffers allowed for assignment of spectral features to
      both five- and six-coordinate heme. Five-coordinate heme is suggested to be
      representative of "native" enzyme, since this species was predominant in the
      enzyme examined immediately after one chromatographic protocol. Quantum
      mechanically mixed spin heme is the most abundant form in such partially purified
      enzyme. Reduction and reoxidation of six-coordinate KatG or the addition of
      glycerol or isoniazid restored five-coordinate heme iron, consistent with
      displacement of a weakly bound distal water molecule. The rate of formation of
      KatG Compound I is not retarded by the presence of six-coordinate heme either in
      wild-type KatG or in a mutant (KatG[Y155S]) associated with isoniazid resistance,
      which contains abundant six-coordinate heme. These results reveal a number of
      similarities and differences between KatG and other Class I peroxidases.

PMID- 12506109
TI  - Kinetic and catalytic properties of dimeric KpnI DNA methyltransferase.
AB  - KpnI DNA-(N(6)-adenine)-methyltransferase (KpnI MTase) is a member of a
      restriction-modification (R-M) system in Klebsiella pneumoniae and recognizes the
      sequence 5'-GGTACC-3'. It modifies the recognition sequence by transferring the
      methyl group from S-adenosyl-l-methionine (AdoMet) to the N(6) position of
      adenine residue. KpnI MTase occurs as a dimer in solution as shown by gel
      filtration and chemical cross-linking analysis. The nonlinear dependence of
      methylation activity on enzyme concentration indicates that the functionally
      active form of the enzyme is also a dimer. Product inhibition studies with KpnI
      MTase showed that S-adenosyl-l-homocysteine is a competitive inhibitor with
      respect to AdoMet and noncompetitive inhibitor with respect to DNA. The
      methylated DNA showed noncompetitive inhibition with respect to both DNA and
      AdoMet. A reduction in the rate of methylation was observed at high
      concentrations of duplex DNA. The kinetic analysis where AdoMet binds first
      followed by DNA, supports an ordered bi bi mechanism. After methyl transfer,
      methylated DNA dissociates followed by S-adenosyl-l-homocysteine. Isotope
      partitioning analysis showed that KpnI MTase-AdoMet complex is catalytically
      active.

PMID- 12506110
TI  - Defective activation of c-Src in cystic fibrosis airway epithelial cells results
      in loss of tumor necrosis factor-alpha-induced gap junction regulation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) signaling is central to the transmission
      of the innate immune response and subsequent activation of the adaptive immune
      system. The functioning of both systems is required for optimal clearance of
      pathogens from the airways. In cystic fibrosis (CF), dysfunction of the CF
      transmembrane conductance regulator (CFTR) is associated with recurrent pulmonary
      infections despite an intense inflammatory and immune response. We reported
      recently that TNF-alpha decreased gap junction connectivity in non-CF airway
      cells, a mechanism that was absent in CF cells expressing the DeltaPhe-508 mutant
      of CFTR. We have now identified the tyrosine kinase c-Src as a possible pathway
      between the mediators of inflammation and the gap junction protein connexin43
      (Cx43). Indeed, TNF-alpha increased the proportion of activated c-Src in non-CF
      airway cells. Moreover, pharmacological antagonists and expression in non-CF
      cells of a dominant negative construct of c-Src prevented Cx43 channel closure by
      TNF-alpha. Finally, gap junction channel closure was prevented by expression of a
      Cx43 mutant lacking tyrosine phosphorylation sites for c-Src. Additional
      experiments showed that activation of c-Src was defective in CF airway cells but
      rescued in CFTR-corrected CF cells. These data suggest that CFTR dysfunction is
      associated with altered TNF-alpha signaling, resulting in the persistence of gap
      junction connectivity in CF airway cells. We propose that altered regulation of c
      Src may contribute to the dysregulated inflammatory response that is
      characteristic of the CF phenotype.

PMID- 12506111
TI  - Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP.
AB  - The apoptosome is a multiprotein complex comprising Apaf-1, cytochrome c, and
      caspase-9 that functions to activate caspase-3 downstream of mitochondria in
      response to apoptotic signals. Binding of cytochrome c and dATP to Apaf-1 in the
      cytosol leads to the assembly of a heptameric complex in which each Apaf-1
      subunit is bound noncovalently to a procaspase-9 subunit via their respective
      CARD domains. Assembly of the apoptosome results in the proteolytic cleavage of
      procaspase-9 at the cleavage site PEPD(315) to yield the large (p35) and small
      (p12) caspase-9 subunits. In addition to the PEPD site, caspase-9 contains a
      caspase-3 cleavage site (DQLD(330)), which when cleaved, produces a smaller p10
      subunit in which the NH(2)-terminal 15 amino acids of p12, including the XIAP
      BIR3 binding motif, are removed. Using purified proteins in a reconstituted
      reaction in vitro, we have assessed the relative impact of Asp(315) and Asp(330)
      cleavage on caspase-9 activity within the apoptosome. In addition, we
      characterized the effect of caspase-3 feedback cleavage of caspase-9 on the rate
      of caspase-3 activation, and the potential ramifications of Asp(330) cleavage on
      XIAP-mediated inhibition of the apoptosome. We have found that cleavage of
      procaspase-9 at Asp(330) to generate p35, p10 or p37, p10 forms resulted in a
      significant increase (up to 8-fold) in apoptosome activity compared with p35/p12.
      The significance of this increase was demonstrated by the near complete loss of
      apoptosome-mediated caspase-3 activity when a point mutant (D330A) of procaspase
      9 was substituted for wild-type procaspase-9 in the apoptosome. In addition,
      cleavage at Asp(330) exposed a novel p10 NH(2)-terminal peptide motif (AISS) that
      retained the ability to mediate XIAP inhibition of caspase-9. Thus, whereas
      feedback cleavage of caspase-9 by caspase-3 significantly increases the activity
      of the apoptosome, it does little to attenuate its sensitivity to inhibition by
      XIAP.

PMID- 12506112
TI  - Apoptosis in leukemia cells is accompanied by alterations in the levels and
      localization of nucleolin.
AB  - Molecular defects in apoptotic pathways are thought to often contribute to the
      abnormal expansion of malignant cells and their resistance to chemotherapy.
      Therefore, a comprehensive knowledge of the mechanisms controlling induction of
      apoptosis and subsequent cellular disintegration could result in improved methods
      for prognosis and treatment of cancer. In this study, we have examined apoptosis
      induced alterations in two proteins, nucleolin and poly(ADP-ribose) polymerase-1
      (PARP-1), in U937 leukemia cells. Nucleolin is expressed at high levels in
      malignant cells, and it is a multifunctional and mobile protein that can shuttle
      among the nucleolus, nucleoplasm, cytoplasm, and plasma membrane. Here, we report
      our findings that UV irradiation or camptothecin treatment of U937 cells induced
      apoptosis and caused a significant change in the levels and localization of
      nucleolin within the nucleus. Additionally, nucleolin levels were dramatically
      decreased in extracts containing the cytoplasm and plasma membrane. These
      alterations could be abrogated by pre-incubation with an inhibitor of PARP-1 (3
      aminobenzamide), and our data support a potential role for nucleolin in removing
      cleaved PARP-1 from dying cells. Furthermore, both nucleolin and cleaved PARP-1
      were detected in the culture medium of cells undergoing apoptosis, associated
      with particles of a size consistent with apoptotic bodies. These results indicate
      that nucleolin plays an important role in apoptosis, and could be a useful marker
      for assessing apoptosis or detecting apoptotic bodies. In addition, the data
      provide a possible explanation for the appearance of nucleolin and PARP-1
      autoantibodies in some autoimmune diseases.

PMID- 12506113
TI  - High-affinity, non-sequence-specific RNA binding by the open reading frame 1
      (ORF1) protein from long interspersed nuclear element 1 (LINE-1).
AB  - Long interspersed nuclear element 1 (LINE-1 or L1) is an interspersed repeated
      DNA found in mammalian genomes. L1 achieved its high copy number by
      retrotransposition, a process that requires the two L1-encoded proteins, ORF1p
      and ORF2p. The role of ORF1p in the retrotransposition cycle is incompletely
      understood, but it is known to bind single-stranded nucleic acids and act as a
      nucleic acid chaperone. This study assesses the nature and specificity of the
      interaction of ORF1p with RNA. Results of coimmunoprecipitation experiments
      demonstrate that ORF1p preferentially binds a single T1 nuclease digestion
      product of 38 nucleotides (nt) within the full-length mouse L1 transcript. The 38
      nt fragment is localized within L1 RNA and found to be sufficient for binding by
      ORF1p but not necessary, because its complement is also efficiently
      coimmunoprecipitated, as are all sequences 38 nt or longer. Results of
      nitrocellulose filter-binding assays demonstrate that the binding of ORF1p to RNA
      does not require divalent cations but is sensitive to the concentration of
      monovalent cation. Both sense and antisense transcripts bind with apparent K(D)s
      in the low nanomolar range. The results of both types of assay unambiguously
      support the conclusion that purified ORF1p from mouse L1 is a high-affinity, non
      sequence-specific RNA binding protein.

PMID- 12506114
TI  - Roles of aromatic residues in the structure and biological activity of the small
      cytokine, growth-blocking peptide (GBP).
AB  - Growth-blocking peptide (GBP) is a small (25 amino acids) insect cytokine with a
      variety of functions: controlling the larval development of lepidopteran insects,
      acting as a mitogen for various types of cultured cells, and stimulating insect
      blood cells. The aromatic residues of GBP (Phe-3, Tyr-11, and Phe-23) are highly
      conserved in the ENF peptide family found in lepidopteran insects. We
      investigated the relationship between the biological activities and structural
      properties of a series of GBP mutants, in which each of the three aromatic
      residues is replaced by a different residue. The results of the hemocytes
      stimulating assays of GBP mutants indicated that Phe-3 is the key residue in this
      activity: Ala or Tyr replacement resulted in significant loss of the activity,
      but Leu replacement did not. The replacements of other aromatic residues hardly
      affected the activity. On the other hand, NMR analysis of the mutants suggested
      that Tyr-11 is a key residue for maintaining the core structure of GBP.
      Surprisingly, the Y11A mutant maintained its biological activity, although its
      native-like secondary structure was disordered. Detailed analyses of the (15)N
      labeled Y11A mutant by heteronuclear NMR spectroscopy showed that the native-like
      beta-sheet structure of Y11A was induced by the addition of 2,2,2
      trifluoroethanol. The results suggest that Y11A has a tendency to form a native
      like structure, and this property may give the Y11A mutant native-like activity.

PMID- 12506115
TI  - Modulation of gene expression by cancer chemopreventive dithiolethiones through
      the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival.
AB  - Enzyme inducers such as 3H-1,2-dithiole-3-thione (D3T) enhance the detoxication
      of environmental carcinogens and protect against neoplasia. The putative
      molecular sensor for inducers is Keap1, a sulfhydryl-rich protein that sequesters
      the transcription factor Nrf2 in the cytoplasm. Expression of these detoxication
      enzymes is blunted in nrf2-deficient mice; moreover, these mice are more
      sensitive to carcinogenesis, and the protective actions of dithiolethiones are
      lost with nrf2 disruption. Hepatic gene expression profiles were examined by
      oligonucleotide microarray analysis in vehicle- or D3T-treated wild-type mice as
      well as in nrf2 single and keap1-nrf2 double knockout mice to identify those
      genes regulated by the Keap1-Nrf2 pathway. Transcript levels of 292 genes were
      elevated in wild-type mice 24 h after treatment with D3T; 79% of these genes were
      induced in wild-type, but not nrf2-deficient mice. These nrf2-dependent, D3T
      inducible genes included known detoxication and antioxidative enzymes. Unexpected
      clusters included genes for chaperones, protein trafficking, ubiquitin/26 S
      proteasome subunits, and signaling molecules. Gene expression patterns in keap1
      nrf2 double knockout mice were similar to those in nrf2-single knockout mice. D3T
      also led to nrf2-dependent repression of 31 genes at 24 h; principally genes
      related to cholesterol/lipid biosynthesis. Collectively, D3T increases the
      expression of genes through the Keap1-Nrf2 signaling pathway that directly
      detoxify toxins and generate essential cofactors such as glutathione and reducing
      equivalents. Induction of nrf2-dependent genes involved in the recognition and
      repair/removal of damaged proteins expands the role of this pathway beyond
      primary control of electrophilic and oxidative stresses into secondary protective
      actions that enhance cell survival.

PMID- 12506116
TI  - H3 relaxin is a specific ligand for LGR7 and activates the receptor by
      interacting with both the ectodomain and the exoloop 2.
AB  - Leucine-rich repeat-containing, G protein-coupled receptors (LGRs) represent a
      unique subgroup of G protein-coupled receptors with a large ectodomain. Recent
      studies demonstrated that relaxin activates two orphan LGRs, LGR7 and LGR8,
      whereas INSL3/Leydig insulin-like peptide specifically activates LGR8. Human
      relaxin 3 (H3 relaxin) was recently discovered as a novel ligand for relaxin
      receptors. Here, we demonstrate that H3 relaxin activates LGR7 but not LGR8.
      Taking advantage of the overlapping specificity of these three ligands for the
      two related LGRs, chimeric receptors were generated to elucidate the mechanism of
      ligand activation of LGR7. Chimeric receptor LGR7/8 with the ectodomain from LGR7
      but the transmembrane region from LGR8 maintains responsiveness to relaxin but
      was less responsive to H3 relaxin based on ligand stimulation of cAMP production.
      The decreased ligand signaling was accompanied by decreases in the ability of H3
      relaxin to compete for (33)P-relaxin binding to the chimeric receptor. However,
      replacement of the exoloop 2, but not exoloop 1 or 3, of LGR7 to the chimeric
      LGR7/8 restored ligand binding and receptor-mediated cAMP production. These
      results suggested that activation of LGR7 by H3 relaxin involves specific binding
      of the ligand to both the ectodomain and the exoloop 2, thus providing a model
      with which to understand the molecular basis of ligand signaling for this unique
      subgroup of G protein-coupled receptors.

PMID- 12506117
TI  - Endothelial nitric-oxide synthase enhances lipopolysaccharide-stimulated tumor
      necrosis factor-alpha expression via cAMP-mediated p38 MAPK pathway in
      cardiomyocytes.
AB  - The purpose of this study was to investigate the role of endothelial nitric-oxide
      synthase (eNOS), cAMP, and p38 MAPK in tumor necrosis factor-alpha (TNF-alpha)
      expression induced by lipopolysaccharide (LPS). LPS dose- and time-dependently
      induced phosphorylation of p38 MAPK and TNF-alpha expression in neonatal mouse
      cardiomyocytes. TNF-alpha expression was preceded by p38 MAPK phosphorylation,
      and selective inhibition of p38 MAPK abrogated LPS-induced TNF-alpha expression.
      Deficiency in eNOS decreased basal and LPS-stimulated TNF-alpha expression in
      cardiomyocytes. NOS inhibitor l-NAME attenuated LPS-induced p38 MAPK
      phosphorylation and TNF-alpha production in wild-type cardiomyocytes, whereas NO
      donor 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (DETA-NO) (2 microm) or
      overexpression of eNOS by adenoviral gene transfer restored the response of eNOS(
      /-) cardiomyocytes to LPS. These effects of NO were mediated through cAMP
      dependent pathway based on the following facts. First, deficiency in eNOS
      decreased basal levels of intracellular cAMP, and DETA-NO elevated intracellular
      cAMP levels in eNOS(-/-) cardiomyocytes. Second, a cAMP analogue 8-Br-cAMP
      mimicked the effect of NO in eNOS(-/-) cardiomyocytes. Third, either inhibition
      of cAMP or cAMP-dependent protein kinase attenuated LPS-stimulated p38 MAPK
      phosphorylation and TNF-alpha production in wild-type cardiomyocytes. In
      conclusion, eNOS enhances LPS-stimulated TNF-alpha expression in cardiomyocytes.
      Activation of p38 MAPK is essential in LPS-stimulated TNF-alpha expression.
      Moreover, the effects of NO on LPS-stimulated TNF-alpha expression are mediated
      through cAMP/cAMP-dependent protein kinase-dependent p38 MAPK pathway in neonatal
      cardiomyocytes.

PMID- 12506118
TI  - The amyloid precursor-like protein 2 and the adenoviral E3/19K protein both bind
      to a conformational site on H-2Kd and regulate H-2Kd expression.
AB  - A protein of unknown physiological function, called amyloid precursor-like
      protein 2 (APLP2), forms an association with the murine class I molecule K(d)
      that is up-regulated by the presence of the adenoviral protein E3/19K. We have
      extended these findings to show that APLP2 and E3/19K associate preferentially
      with folded K(d) and not with the open form. APLP2 was detectable at the cell
      surface, but its surface expression was not up-regulated by the concurrent
      expression of K(d). Experimental down-regulation of APLP2 expression caused a
      consistent increase in the surface expression of K(d), indicating that APLP2
      normally reduces K(d) surface expression. These data suggest a role for APLP2 in
      controlling the maturation of major histocompatibility complex class I molecules.

PMID- 12506119
TI  - CAMP-dependent protein kinase enhances CYP17 transcription via MKP-1 activation
      in H295R human adrenocortical cells.
AB  - Steroid hormone biosynthesis in the adrenal cortex is controlled by
      adrenocorticotropin (ACTH), which increases intracellular cAMP, resulting in the
      activation of cAMP-dependent protein kinase(PKA) and subsequent increase in
      steroidogenic gene transcription. We have found that a dual-specificity
      phosphatase is essential for conveying ACTH/cAMP-stimulated transcription of
      several steroidogenic genes in the human adrenal cortex. In the present study,
      the role of mitogen-activated protein kinase phosphatase-1 (MKP-1), a nuclear
      dual-specificity phosphatase, in the transcriptional activation of human CYP17
      (hCYP17) in H295R human adrenocortical cells is established. Stimulation of H295R
      cells with dibutyryl-cAMP (Bt(2)cAMP) induces MKP-1 mRNA and protein expression
      within 30 min of exposure. In transient-transfection studies, transcriptional
      activity of an hCYP17 promoter-reporter construct was increased by Bt(2)cAMP and
      by overexpression of PKA or MKP-1. Furthermore, PKA phosphorylated an MKP-1
      glutathione S-transferase fusion protein in in vitro assays and Bt(2)cAMP
      increased (32)P associated with MKP-1 that was immunoprecipitated from H295R
      cells. Finally, silencing MKP-1 expression using antisense oligonucleotides
      attenuated cAMP-stimulated hCYP17 expression, whereas silencing of ERK1/2
      increased hCYP17 expression. These findings demonstrate integral roles for MKP-1
      and ERK1/2 via regulation of the phosphorylation state of steroidogenic factor-1
      (SF-1) in mediating ACTH/cAMP-dependent transcription of hCYP17, thereby
      maintaining the balance between transcriptional activation and repression.

PMID- 12506120
TI  - Regulation of protein kinase Cnu by the B-cell antigen receptor.
AB  - Diacylglycerol-dependent signaling plays an important role in signal transduction
      through T- and B-lymphocyte antigen receptors. Recently, a novel serine-threonine
      kinase of the protein kinase C (PKC) family has been described and designated as
      PKCnu. PKCnu has two putative diacylglycerol binding C1 domains, suggesting that
      it may participate in a novel diacylglycerol-mediated signaling pathway. Here we
      show that both endogenous and recombinant PKCnu are trans-located to the plasma
      membrane and activated by the diacylglycerol mimic phorbol 12-myristate 13
      acetate. Mutational analysis demonstrates that PKCnu activation is dependent on
      trans-phosphorylation of two conserved activation loop serine residues. We also
      find that PKCnu is an important physiologic target of the B-cell receptor (BCR),
      because PKCnu is found to be abundantly expressed in chicken and human B-cell
      lines and, in addition, exhibits robust activation after BCR engagement. Genetic
      and pharmacologic analyses of BCR-mediated PKCnu activation indicate that it
      requires intact phospholipase Cgamma and PKC signaling pathways. Furthermore, in
      co-transfection assays, PKCnu can be trans-phosphorylated by the novel PKC
      isozymes PKCepsilon, PKCeta, or PKCtheta but not the classical PKC enzyme,
      PKCalpha. Taken together, these results suggest that PKCnu is an important
      component of signaling pathways downstream from novel PKC enzymes after B-cell
      receptor engagement.

PMID- 12506121
TI  - Mutagenesis of the gamma-carboxyglutamic acid domain of human factor VII to
      generate maximum enhancement of the membrane contact site.
AB  - Site-directed mutagenesis of the 40 N-terminal residues (gamma-carboxyglutamic
      acid domain) of blood clotting factor VII was carried out to identify sites that
      improve membrane affinity. Improvements and degree of change included P10Q (2
      fold), K32E (13-fold), and insertion of Tyr at position 4 (2-fold). Two other
      beneficial changes, D33F (2-fold) and A34E (1.5-fold), may exert their impact via
      influence of K32E. The modification D33E (5.2-fold) also resulted in substantial
      improvement. The combined mutant with highest affinity, (Y4)P10Q/K32E/D33F/A34E,
      showed 150-296-fold enhancement over wild-type factor VIIa, depending on the
      assay used. Undercarboxylation of Glu residues at positions 33 and 34 may result
      in an underestimate of the true contributions of gamma-carboxyglutamic acid at
      these positions. Except for the Tyr(4) mutant, all other beneficial mutations
      were located on the same surface of the protein, suggesting a possible membrane
      contact region. An initial screening assay was developed that provided faithful
      evaluation of mutants in crude mixtures. Overall, the results suggest features of
      membrane binding by vitamin K-dependent proteins and provide reagents that may
      prove useful for research and therapy.

PMID- 12506122
TI  - Negative regulation of MAPKK by phosphorylation of a conserved serine residue
      equivalent to Ser212 of MEK1.
AB  - The MAPKKs MEK1 and MEK2 are activated by phosphorylation, but little is known
      about how these enzymes are inactivated. Here, we show that MEK1 is
      phosphorylated in vivo at Ser(212), a residue conserved among all MAPKK family
      members. Mutation of Ser(212) to alanine enhanced the basal activity of MEK1,
      whereas the phosphomimetic aspartate mutation completely suppressed the
      activation of both wild-type MEK1 and the constitutively activated
      MEK1(S218D/S222D) mutant. Phosphorylation of Ser(212) did not interfere with
      activating phosphorylation of MEK1 at Ser(218)/Ser(222) or with binding to ERK2
      substrate. Importantly, mimicking phosphorylation of the equivalent Ser(212)
      residue of the yeast MAPKKs Pbs2p and Ste7p similarly abrogated their biological
      function. Our findings suggest that Ser(212) phosphorylation represents an
      evolutionarily conserved mechanism involved in the negative regulation of MAPKKs.

PMID- 12506123
TI  - Dynamic shuttling and intranuclear mobility of nuclear hormone receptors.
AB  - We expressed green fluorescent protein (GFP) chimeras of estrogen, retinoic acid,
      and thyroid hormone receptors (ERs, RARs, and TRs, respectively) in HeLa cells to
      examine nucleocytoplasmic shuttling and intranuclear mobility of nuclear hormone
      receptors (NRs) by confocal microscopy. These receptors were predominantly in the
      nucleus and, interestingly, underwent intranuclear reorganization after ligand
      treatment. Nucleocytoplasmic shuttling was demonstrated by heterokaryon
      experiments and energy-dependent blockade of nuclear import and leptomycin
      dependent blockade of nuclear export. Ligand addition decreased shuttling by GFP
      ER, whereas heterodimerization with retinoid X receptor helped maintain TR and
      RAR within the nucleus. Intranuclear mobility of the GFP-NRs was studied by
      fluorescence recovery after photo-bleaching +/- cognate ligands. Both GFP-TR and
      GFP-RAR moved rapidly in the nucleus, and ligand binding did not significantly
      affect their mobility. In contrast, estrogen binding decreased the mobility of
      GFP-ER and also increased the fraction of GFP-ER that was unable to diffuse.
      These effects were even more pronounced with tamoxifen. Co-transfection of the co
      activator, SRC-1, further slowed the mobility of liganded GFP-ER. Our findings
      suggest estradiol and tamoxifen exert differential effects on the intranuclear
      mobility of GFP-ER. They also show that ligand-binding and protein-protein
      interactions can affect the intracellular mobility of some NRs and thereby may
      contribute to their biological activity.

PMID- 12506124
TI  - The formation and activity of PP2A holoenzymes do not depend on the isoform of
      the catalytic subunit.
AB  - The protein phosphatase 2A holoenzyme is composed of one catalytic C subunit, one
      regulatory/scaffolding A subunit, and one regulatory B subunit. The core enzyme
      consists of A and C subunits only. The A and C subunits both exist as two closely
      related isoforms, alpha and beta. The B subunits belong to four weakly related or
      unrelated families, designated B, B', B", and B"', with multiple members in each
      family. The existence of two A and two C subunit isoforms permits the formation
      of four core enzymes, AalphaCalpha, AalphaCbeta, AbetaCalpha, and AbetaCbeta, and
      each core enzyme could in theory give rise to multiple holoenzymes. Differences
      between Calpha and Cbeta in expression and subcellular localization during early
      embryonic development have been reported, which imply that Calpha and Cbeta have
      different functions. To address the question of whether these differences might
      be caused by enzymatic differences between Calpha and Cbeta, we purified six
      holoenzymes composed of AalphaCalpha or AalphaCbeta core enzyme and B subunits
      from the B, B', or B" families. In addition, we purified four holoenzymes
      composed of AbetaCalpha or AbetaCbeta and B'alpha1 or B"/PR72. The phosphatase
      activity of each purified form was assayed using myelin basic protein and histone
      H1 as substrates. We found that Calpha and Cbeta have identical phosphatase
      activities when associated with the same A and B subunits. Furthermore, no
      difference was found between Calpha and Cbeta in binding A or B subunits. These
      data suggest that the distinct functions of Calpha and Cbeta are not based on
      differences in enzymatic activity or subunit interaction. The implications for
      the relationship between the structure and function of Calpha and Cbeta are
      discussed.

PMID- 12506125
TI  - Receptor protein tyrosine phosphatases in nervous system development.
AB  - Receptor protein tyrosine phosphatases (RPTPs) are key regulators of neuronal
      morphogenesis in a variety of different vertebrate and invertebrate systems, yet
      the mechanisms by which these proteins regulate central nervous system
      development are poorly understood. In the past few years, studies have begun to
      outline possible models for RPTP function by demonstrating in vivo roles for
      RPTPs in axon outgrowth, guidance, and synaptogenesis. In addition, the crystal
      structures of several RPTPs have been solved, numerous downstream effectors of
      RPTP signaling have been identified, and a small number of RPTP ligands have been
      described. In this review, we focus on how RPTPs transduce signals from the
      extracellular environment to the cytoplasm, using a detailed comparative analysis
      of the different RPTP subfamilies. Focusing on the roles RPTPs play in the
      development of the central nervous system, we discuss how the elucidation of RPTP
      crystal structures, the biochemical analysis of phosphatase enzyme catalysis, and
      the characterization of complex signal transduction cascades downstream of RPTPs
      have generated testable models of RPTP structure and function.

PMID- 12506126
TI  - Blood glucose dynamics and control of meal initiation: a pattern detection and
      recognition theory.
AB  - A new framework for understanding the control of feeding behavior, with special
      emphasis on the evolution of hunger, the initiation of feeding, and its
      dependence on patterns of blood glucose, is the subject of this review. A
      perspective on the current status and future directions of this search for a more
      complete understanding of the regulation of feeding behavior in laboratory rats
      and humans is presented including theoretical and experimental components. First,
      a historical perspective on the role of blood glucose in the control of feeding
      is presented. Next, the theoretical approaches that have been applied to the
      control of feeding and had a strong influence on experimental feeding research
      are summarized. This is followed by a statement and overview of a current theory
      that has emerged from studies of the role of transient declines in blood glucose
      in the control of meal initiation. The current working hypothesis that transient
      declines in blood glucose are endogenous metabolic patterns that are detected and
      recognized by the central nervous system and are mapped into meal initiation in
      rats and are correlated with meal requests in humans are then presented. Then,
      the experimental studies on meal initiation and its dependence on patterns of
      blood glucose, first in rats and then in humans, are reviewed in detail. Finally,
      the future directions of the work, limitations, and the implications for the
      understanding of the control of feeding behavior and the regulation of energy
      balance are discussed.

PMID- 12506127
TI  - Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile
      performance, and rhythmicity.
AB  - Experimental work during the past 15 years has demonstrated that endothelial
      cells in the heart play an obligatory role in regulating and maintaining cardiac
      function, in particular, at the endocardium and in the myocardial capillaries
      where endothelial cells directly interact with adjacent cardiomyocytes. The
      emerging field of targeted gene manipulation has led to the contention that
      cardiac endothelial-cardiomyocytal interaction is a prerequisite for normal
      cardiac development and growth. Some of the molecular mechanisms and cellular
      signals governing this interaction, such as neuregulin, vascular endothelial
      growth factor, and angiopoietin, continue to maintain phenotype and survival of
      cardiomyocytes in the adult heart. Cardiac endothelial cells, like vascular
      endothelial cells, also express and release a variety of auto- and paracrine
      agents, such as nitric oxide, endothelin, prostaglandin I(2), and angiotensin II,
      which directly influence cardiac metabolism, growth, contractile performance, and
      rhythmicity of the adult heart. The synthesis, secretion, and, most importantly,
      the activities of these endothelium-derived substances in the heart are closely
      linked, interrelated, and interactive. It may therefore be simplistic to try and
      define their properties independently from one another. Moreover, in relation
      specifically to the endocardial endothelium, an active transendothelial
      physicochemical gradient for various ions, or blood-heart barrier, has been
      demonstrated. Linkage of this blood-heart barrier to the various other
      endothelium-mediated signaling pathways or to the putative vascular endothelium
      derived hyperpolarizing factors remains to be determined. At the early stages of
      cardiac failure, all major cardiovascular risk factors may cause cardiac
      endothelial activation as an adaptive response often followed by cardiac
      endothelial dysfunction. Because of the interdependency of all endothelial
      signaling pathways, activation or disturbance of any will necessarily affect the
      others leading to a disturbance of their normal balance, leading to further
      progression of cardiac failure.

PMID- 12506128
TI  - Molecular physiology of low-voltage-activated t-type calcium channels.
AB  - T-type Ca2+ channels were originally called low-voltage-activated (LVA) channels
      because they can be activated by small depolarizations of the plasma membrane. In
      many neurons Ca2+ influx through LVA channels triggers low-threshold spikes,
      which in turn triggers a burst of action potentials mediated by Na+ channels.
      Burst firing is thought to play an important role in the synchronized activity of
      the thalamus observed in absence epilepsy, but may also underlie a wider range of
      thalamocortical dysrhythmias. In addition to a pacemaker role, Ca2+ entry via T
      type channels can directly regulate intracellular Ca2+ concentrations, which is
      an important second messenger for a variety of cellular processes. Molecular
      cloning revealed the existence of three T-type channel genes. The deduced amino
      acid sequence shows a similar four-repeat structure to that found in high-voltage
      activated (HVA) Ca2+ channels, and Na+ channels, indicating that they are
      evolutionarily related. Hence, the alpha1-subunits of T-type channels are now
      designated Cav3. Although mRNAs for all three Cav3 subtypes are expressed in
      brain, they vary in terms of their peripheral expression, with Cav3.2 showing the
      widest expression. The electrophysiological activities of recombinant Cav3
      channels are very similar to native T-type currents and can be differentiated
      from HVA channels by their activation at lower voltages, faster inactivation,
      slower deactivation, and smaller conductance of Ba2+. The Cav3 subtypes can be
      differentiated by their kinetics and sensitivity to block by Ni2+. The goal of
      this review is to provide a comprehensive description of T-type currents, their
      distribution, regulation, pharmacology, and cloning.

PMID- 12506129
TI  - Transport of exogenous growth factors and cytokines to the cytosol and to the
      nucleus.
AB  - In recent years a number of growth factors, cytokines, protein hormones, and
      other proteins have been found in the nucleus after having been added externally
      to cells. This review evaluates the evidence that translocation takes place and
      discusses possible mechanisms. As a demonstration of the principle that
      extracellular proteins can penetrate cellular membranes and reach the cytosol, a
      brief overview of the penetration mechanism of protein toxins with intracellular
      sites of action is given. Then problems and pitfalls in attempts to demonstrate
      the presence of proteins in the cytosol and in the nucleus as opposed to
      intracellular vesicular compartments are discussed, and some new approaches to
      study this are described. A detailed overview of the evidence for translocation
      of fibroblast growth factor, HIV-Tat, interferon-gamma, and other proteins where
      there is evidence for intracellular action is given, and translocation mechanisms
      are discussed. It is concluded that although there are many pitfalls, the bulk of
      the experiments indicate that certain proteins are indeed able to enter the
      cytosol and nucleus. Possible roles of the internalized proteins are discussed.

PMID- 12506130
TI  - Regulation of amino acid and glucose transporters in endothelial and smooth
      muscle cells.
AB  - While transport processes for amino acids and glucose have long been known to be
      expressed in the luminal and abluminal membranes of the endothelium comprising
      the blood-brain and blood-retinal barriers, it is only within the last decades
      that endothelial and smooth muscle cells derived from peripheral vascular beds
      have been recognized to rapidly transport and metabolize these nutrients. This
      review focuses principally on the mechanisms regulating amino acid and glucose
      transporters in vascular endothelial cells, although we also summarize recent
      advances in the understanding of the mechanisms controlling membrane transport
      activity and expression in vascular smooth muscle cells. We compare the
      specificity, ionic dependence, and kinetic properties of amino acid and glucose
      transport systems identified in endothelial cells derived from cerebral, retinal,
      and peripheral vascular beds and review the regulation of transport by vasoactive
      agonists, nitric oxide (NO), substrate deprivation, hypoxia, hyperglycemia,
      diabetes, insulin, steroid hormones, and development. In view of the importance
      of NO as a modulator of vascular tone under basal conditions and in disease and
      chronic inflammation, we critically review the evidence that transport of L
      arginine and glucose in endothelial and smooth muscle cells is modulated by
      bacterial endotoxin, proinflammatory cytokines, and atherogenic lipids. The
      recent colocalization of the cationic amino acid transporter CAT-1 (system y(+)),
      nitric oxide synthase (eNOS), and caveolin-1 in endothelial plasmalemmal caveolae
      provides a novel mechanism for the regulation of NO production by L-arginine
      delivery and circulating hormones such insulin and 17beta-estradiol.

PMID- 12506131
TI  - Cell biology of the glomerular podocyte.
AB  - Glomerular podocytes are highly specialized cells with a complex
      cytoarchitecture. Their most prominent features are interdigitated foot processes
      with filtration slits in between. These are bridged by the slit diaphragm, which
      plays a major role in establishing the selective permeability of the glomerular
      filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most
      glomerular diseases. New technical approaches have led to a considerable increase
      in our understanding of podocyte biology including protein inventory, composition
      and arrangement of the cytoskeleton, receptor equipment, and signaling pathways
      involved in the control of ultrafiltration. Moreover, disturbances of podocyte
      architecture resulting in the retraction of foot processes and proteinuria appear
      to be a common theme in the progression of acquired glomerular disease. In
      hereditary nephrotic syndromes identified over the last 2 years, all mutated gene
      products were localized in podocytes. This review integrates our recent
      physiological and molecular understanding of the role of podocytes during the
      maintenance and failure of the glomerular filtration barrier.

PMID- 12506132
TI  - Metabolism of Cisplatin to a nephrotoxin in proximal tubule cells.
AB  - Cisplatin, a commonly used chemotherapeutic agent, is nephrotoxic. The mechanism
      by which cisplatin selectively kills the proximal tubule cells was heretofore
      unknown. Recent studies in mice and rats have shown that the nephrotoxicity of
      cisplatin can be blocked by acivicin or (aminooxy)acetic acid, the same enzyme
      inhibitors that block the metabolic activation of a series of nephrotoxic
      halogenated alkenes. In this study, it was hypothesized that cisplatin is
      activated in the kidney to a toxic metabolite through the same pathway that has
      been shown to activate the halogenated alkenes. This activation begins with the
      formation of a glutathione-conjugate that is metabolized to a cysteinyl-glycine
      conjugate, to a cysteine-conjugate, and finally to a reactive thiol. In this
      study, a protocol was developed in which confluent monolayers of LLC-PK(1) cells
      were exposed to clinically relevant concentrations of cisplatin or cisplatin
      conjugate for 3 h. Cell viability was assayed at 72 h. The role of gamma-glutamyl
      transpeptidase (GGT) and cysteine-S-conjugate beta-lyase in the metabolism of
      each of the cisplatin-conjugates was investigated. Pre-incubation of cisplatin
      with glutathione, cysteinyl-glycine, or N-acetyl-cysteine to allow for the
      spontaneous formation of cisplatin-conjugates increased the toxicity of cisplatin
      toward LLC-PK(1) cells. Inhibition of GGT activity showed that GGT was necessary
      only for the toxicity of the cisplatin-glutathione-conjugate. Inhibition of
      cysteine-S-conjugate beta-lyase reduced the toxicity of each of the cisplatin
      conjugates. These data demonstrate that metabolism of cisplatin in proximal
      tubule cells is required for its nephrotoxicity. The elucidation of this pathway
      provides new targets for the inhibition of cisplatin nephrotoxicity.

PMID- 12506133
TI  - Inhibition of prostasin secretion by serine protease inhibitors in the kidney.
AB  - A serine protease, prostasin, has been shown to stimulate the activity of
      amiloride-sensitive sodium channels (ENaC). Prostasin is a
      glycosylphosphatidylinositol-anchored protein that is found free in physiologic
      fluids and tissue culture medium, but the mechanism by which prostasin is
      secreted from the cells has not been elucidated. The current studies found that
      serine protease inhibitor aprotinin blocked the secretion of prostasin in a mouse
      cortical collecting duct (CCD) cell line (M-1 cells). A synthetic serine protease
      inhibitor, nafamostat mesilate (NM), which is commonly used for the treatment of
      pancreatitis and disseminated intravascular coagulation in Japan, also inhibited
      the secretion of prostasin in M-1 cells. Continuous infusion of NM into rats
      resulted in a substantial decrease in urinary prostasin and urinary sodium
      excretion. p-guanidinobenzoic acid and 6-amidino-2-naphtol, catalytically
      inactive metabolites of NM, had no effect on prostasin secretion both in M-1
      cells and in rats. These findings suggest that a serine protease-sensitive
      mechanism is involved in the secretion of prostasin in vitro as well as in vivo.
      Potassium secretion in the CCD is tightly linked to sodium reabsorption through
      EnaC; therefore, NM-induced decrease in prostasin secretion and subsequent
      inhibition of ENaC activity could account for the side effects of hyponatremia
      and/or hyperkalemia that are found sometimes in patients treated with NM. The
      results indicate an important role for prostasin in sodium reabsorption in the
      kidney under pathophysiologic conditions.

PMID- 12506134
TI  - Stimulation of proximal tubular cell apoptosis by albumin-bound fatty acids
      mediated by peroxisome proliferator activated receptor-gamma.
AB  - In nephrotic syndrome, large quantities of albumin enter the kidney tubule. This
      albumin carries with it a heavy load of fatty acids to which the proximal tubule
      cells are exposed at high concentration. It is postulated that exposure to fatty
      acids in this way is injurious to proximal tubule cells. This study has examined
      the ability of fatty acids to interact with peroxisome proliferator-activated
      receptors (PPAR) in primary cultures of human proximal tubule cells. Luciferase
      reporter assays in transiently transfected human proximal tubule cells were used
      to show that albumin bound fatty acids and other agonists activate PPARgamma in a
      dose-dependent manner. One of the consequences of this activation is apoptosis of
      the cells as determined by changes in cell morphology, evidence of PARP cleavage,
      and appearance of DNA laddering. Overexpression of PPARgamma in these cells also
      results in enhanced apoptosis. Both fatty acid-induced PPAR activation and
      apoptosis in these cells can be blocked by PPAR response element decoy
      oligonucleotides. Activation of PPARgamma by the specific agonist PGJ(2) is
      associated with inhibition of cell proliferation, whereas activation by albumin
      bound fatty acids is accompanied by increased proliferation. However, the net
      balance of apoptosis/proliferation favors deletion of cells. These results
      implicate albumin-bound fatty acids as important mediators of tubular injury in
      nephrosis and provide fresh impetus for pursuit of lipid-lowering strategies in
      proteinuric renal disease.

PMID- 12506135
TI  - Ca2+/calmodulin-dependent protein kinase II stimulates c-fos transcription and
      DNA synthesis by a Src-based mechanism in glomerular mesangial cells.
AB  - Mesangial cell growth factors elevate intracellular free [Ca2+]i, but mechanisms
      linking [Ca2+]i to gene expression and DNA synthesis are unclear. This study
      investigated the hypothesis that Ca2+/calmodulin-dependent protein kinase II
      (CaMK II), which is activated by elevated [Ca2+]i, increases c-fos transcription
      and DNA synthesis via a Src-based mechanism. In cultured rat mesangial cells,
      dominant negative Src (SrcK-) blocked activation of the c-fos gene promoter by
      CaMK II 290, a constitutively active form of CaMK IIalpha. Activation of the c
      fos promoter by CaMK II 290 was also blocked by COOH-terminal Src kinase, which
      phosphorylates and inactivates c-Src. A pharmacologic CaMK inhibitor, KN-93, did
      not block activation of the c-fos promoter by ectopically expressed v-Src.
      Stimulation of c-Src by endothelin-1 required CaMK II activity, further
      supporting the notion that CaMK II acts upstream of Src in a signaling cassette.
      Activation of the c-fos promoter by CaMKII290 and Src required the c-fos serum
      response element. Dominant negative SrcK- also blocked induction of DNA synthesis
      in mesangial cells by CaMK II 290. Collectively, these results suggest that in
      mesangial cells Src protein tyrosine kinases act downstream of CaMKII in a
      signaling pathway in which [Ca2+]i induces the c-fos promoter and increases DNA
      synthesis.

PMID- 12506136
TI  - Rho-kinase inhibition blunts renal vasoconstriction induced by distinct signaling
      pathways in vivo.
AB  - In addition to intracellular calcium, which activates myosin light chain (MLC)
      kinase, MLC phosphorylation and hence contraction is importantly regulated by MLC
      phosphatase (MLCP). Recent evidence suggests that distinct signaling cascades of
      vasoactive hormones interact with the Rho/Rho kinase (ROK) pathway, affecting the
      activity of MLCP. The present study measured the impact of ROK inhibition on
      vascular F-actin distribution and on vasoconstriction induced by
      activation/inhibition of distinct signaling pathways in vivo in the
      microcirculation of the split hydronephrotic rat kidney. Local application of the
      ROK inhibitors Y-27632 or HA-1077 induced marked dilation of pre- and
      postglomerular vessels. Activation of phospholipase C with the endothelin ET B
      agonist IRL 1620, inhibition of soluble guanylyl cyclase with 1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or inhibition of adenylyl
      cyclase with the adenosine A1 agonist N6-cyclopentyladenosine (CPA) reduced
      glomerular blood flow (GBF) by about 50% through vasoconstriction at different
      vascular levels. ROK inhibition with Y-27632 or HA-1077, but not protein kinase C
      inhibition with Ro 31-8220, blunted ET B-induced vasoconstriction. Furthermore,
      the reduction of GBF and of vascular diameters in response to ODQ or CPA were
      abolished by pretreatment with Y-27632. ROK inhibitors prevented constriction of
      preglomerular vessels and of efferent arterioles with equal effectiveness.
      Confocal microscopy demonstrated that Y-27632 did not change F-actin content and
      distribution in renal vessels. The results suggest that ROK inhibition might be
      considered as a potent treatment of renal vasoconstriction, because it interferes
      with constriction induced by distinct signaling pathways in renal vessels without
      affecting F-actin structure.

PMID- 12506137
TI  - Cloning of rat homologue of podocin: expression in proteinuric states and in
      developing glomeruli.
AB  - Podocin is identified as a product of the gene mutated in a patient with
      autosomal recessive steroid-resistant nephrotic syndrome. Although podocin is
      reported to be located at the slit diaphragm area, the precise role of podocin
      for maintaining the barrier function of the slit diaphragm has not been clearly
      elucidated. A rat homologue of podocin was cloned, and the expression of podocin
      was investigated and then compared with the nephrin and the ZO-1 expressions in
      rat experimental proteinuric models and in developing glomeruli. Amino acid
      sequences of rat and human podocin are highly homologous (84.3% identity). The
      domain structure of podocin is also highly conserved between rat and human. The
      mRNA expression for podocin was detected in glomeruli and the nerve tissues. The
      localization of podocin has close proximity to that of nephrin in normal adult
      rat glomeruli. Podocin staining was restricted to the basal side of the podocyte
      of the early developing stage, whereas nephrin staining was detected on the
      basolateral surface of podocyte. The redistribution of podocin was observed in
      the anti-nephrin antibody (ANA)-induced nephropathy and puromycin aminonucleoside
      (PAN) nephropathy. The redistribution of podocin paralleled with nephrin in ANA
      nephropathy but not in PAN nephropathy. Podocin is observed at the site of tight
      junction newly formed in proteinuric state in PAN nephropathy. It is postulated
      that podocin is one of the critical components of a slit diaphragm for
      maintaining the barrier function of the glomerular capillary wall.

PMID- 12506138
TI  - p38 Mitogen-activated protein kinase contributes to autoimmune renal injury in
      MRL-Fas lpr mice.
AB  - The phosphorylation of p38 mitogen-activated protein kinase (MAPK) is responsible
      for the production and signal transduction of cytokines and chemokines. This
      study hypothesized that p38 MAPK activation is required for spontaneous
      autoimmune renal injury in MRL-Fas(lpr) mice, resembling human lupus
      erythematosus. FR167653, a specific inhibitor of p38 MAPK, is orally
      administrated from 3 or 4 mo of age in MRL-Fas(lpr) mice (at doses of 10 or
      32mg/kg per day) until 6 mo of age. The phosphorylated p38 MAPK in kidneys of MRL
      Fas(lpr) mice was evaluated. The number of phosphorylated p38 MAPK-positive cells
      was increased in diseased kidneys. The daily oral administration of FR167653
      decreased p38 MAPK phosphorylation in kidneys, especially in a group of mice
      administered FR167653 (32 mg/kg per day) daily from 3 to 6 mo of age. FR167653
      reduced the accumulation of macrophages and T cell and prevented kidney
      pathology, resulting in prolonged survival. In addition, FR167653 reduced
      expression of MCP-1 and TNF-alpha in the diseased kidneys and cultured tubular
      epithelial cells. Furthermore, FR167653 decreased IgG levels in the diseased
      kidneys and circulation. These results suggest that the phosphorylation of p38
      MAPK is required for the pathogenesis of renal injury in MRL-Fas(lpr) mice
      followed by subsequent expression of renal cytokine/chemokine and IgG production.
      This study provides evidence that the regulation of p38 MAPK is a novel target
      for the therapy of renal injury in systemic lupus erythematosus.

PMID- 12506139
TI  - Membrane expression of proteinase 3 is genetically determined.
AB  - Isolated human neutrophils exhibit a bimodal membrane proteinase 3 (PR3)
      expression. PR3 is the main target antigen in Wegener granulomatosis (WG). Cells
      with low expression can be easily distinguished from cell subsets with high
      expression. In a recent study, a large neutrophil subset expressing membrane PR3
      (mPR3+) was a risk factor for systemic ANCA-associated vasculitis. PR3 membrane
      expression patterns are quite stable in a given individual, raising the
      possibility of genetic variance. The aims of this study were: (1) to investigate
      the association of mPR3 expression and the risk of WG in an independent German
      cohort; (2) to test the hypothesis that mPR3 expression on neutrophils is
      genetically influenced; and (3) to investigate whether or not mPR3 expression is
      a function of intracellular PR3 content. mPR3 expression was assessed by FACS
      analysis in isolated human neutrophils. Neutrophil mPR3 expression was studied in
      35 patients with WG, 15 patients with other inflammatory diseases, 125 healthy
      volunteers, and 27 (15 monozygotic and 12 dizygotic) pairs of twins. The
      intracellular PR3 content was assessed by intracellular flow cytometry and by
      Western blotting after separating mPR3 low and high expressing cells by FACSort.
      FACS analysis in a subset of 16 healthy subjects showed a highly conserved PR3
      phenotype in two independent investigations >12 mo apart (r = 0.937). Patients
      with WG demonstrated a significantly higher percentage of mPR3+ neutrophils than
      healthy controls and patients with other inflammatory diseases. The mPR3+
      percentage was highly correlated in MZ twins (r = 0.99) compared with DZ twins (r
      = 0.06). The intracellular PR3 content was not different in persons with low or
      high mPR3 expression, nor was the PR3 content different in cells with low or high
      mPR3 expression within a given individual. These data indicate that WG patients
      have a higher percentage of mPR3-expressing neutrophils. Furthermore, mPR3
      expression is influenced by genetic variance. Finally, mPR3 expression is
      independent of intracellular PR3 content.

PMID- 12506140
TI  - Spectrum of mutations in the gene for autosomal recessive polycystic kidney
      disease (ARPKD/PKHD1).
AB  - Autosomal recessive polycystic kidney disease (ARPKD/PKHD1) is an important cause
      of renal-related and liver-related morbidity and mortality in childhood. Recently
      mutations in the PKHD1 gene on chromosome 6p21.1-p12 have been identified as the
      molecular cause of ARPKD. The longest continuous open reading frame (ORF) is
      encoded by a 67-exon transcript and predicted to yield a 4074-amino acid protein
      ("polyductin") of thus far unknown function. By now, a total of 29 different
      PKHD1 mutations have been described. This study reports mutation screening in 90
      ARPKD patients and identifies mutations in 110 alleles making up a detection rate
      of 61%. Thirty-four of the detected mutations have not been reported previously.
      Two underlying mutations in 40 patients and one mutation in 30 cases are
      disclosed, and no mutation was detected on the remaining chromosomes. Mutations
      were found to be scattered throughout the gene without evidence of clustering at
      specific sites. About 45% of the changes were predicted to truncate the protein.
      All missense mutations were nonconservative, with the affected amino acid
      residues found to be conserved in the murine polyductin orthologue. One recurrent
      missense mutation (T36M) likely represents a mutational hotspot and occurs in a
      variety of populations. Two founder mutations (R496X and V3471G) make up about
      60% of PKHD1 mutations in the Finnish population. Preliminary genotype-phenotype
      correlations could be established for the type of mutation rather than for the
      site of the individual mutation. All patients carrying two truncating mutations
      displayed a severe phenotype with perinatal or neonatal demise. PKHD1 mutation
      analysis is a powerful tool to establish the molecular cause of ARPKD in a given
      family. Direct identification of mutations allows an unequivocal diagnosis and
      accurate genetic counseling even in families displaying diagnostic challenges.

PMID- 12506141
TI  - Effect of chronic renal failure on cardiac contractile function, calcium cycling,
      and gene expression of proteins important for calcium homeostasis in the rat.
AB  - Patients with chronic renal failure frequently develop cardiac hypertrophy and
      diastolic dysfunction; however, the mechanisms by which this occurs are still
      unclear. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy and studied
      for their isolated myocyte function, calcium cycling, and gene expression of
      proteins important in calcium homeostasis after 4 wk. Comparable rats subjected
      to suprarenal aortic banding for the same duration were used for comparison. Rats
      subjected to 5/6 nephrectomy and aortic banding developed comparable
      hypertension; however, rats subjected to 5/6 nephrectomy experienced a greater
      degree of cardiac hypertrophy and downregulation of cardiac sodium potassium
      ATPase (Na+/K+ -ATPase) activity than rats subjected to aortic banding. Moreover,
      cells isolated from the 5/6 nephrectomy rat hearts displayed impaired contractile
      function and altered calcium cycling compared with cells isolated from control or
      aortic constriction rat hearts. The 5/6 nephrectomy rat heart cells displayed a
      prolonged time constant for calcium recovery following stimulation, which
      corresponded to decreases in homogenate sarcoplasmic reticulum calcium ATPase-2a
      (SERCA2a) activity, protein density, and mRNA for SERCA2a. In conclusion, chronic
      renal failure leads to alterations in cardiac gene expression, which produces
      alterations in cardiac calcium cycling and contractile function. These changes
      cannot be explained only by the observed increases in BP.

PMID- 12506142
TI  - Hsp27 associates with actin and limits injury in energy depleted renal epithelia.
AB  - The purpose of the study was to determine whether Hsp27 interacts with actin and
      could protect against selected manifestations of injury from energy depletion in
      renal epithelia. LLC-PK1 cells were stably transfected to overexpress human Hsp27
      tagged with green fluorescence protein (GFP). Transfected expression of the
      labeled Hsp27 did not reduce endogenous Hsp25 levels in the cells compared with
      either nontransfected cells or cells transfected with GFP alone used as the
      transfectant control (G). By fluorescence energy transfer (FRET) between GFP
      tagged Hsp27 and rhodamine phalloidin-decorated actin, minimal interaction was
      found in uninjured control cells. In ATP-depleted cells, Hsp27 was associated
      closely with F-actin at lateral cell boundaries and with aggregated actin within
      the cell body. Less Hsp27 interaction with actin was found during recovery; but
      when adjusted for total phalloidin fluorescence, FRET between Hsp27 and F-actin
      did not change between 2-h ATP depletion and 4-h recovery. Where Hsp27
      association with actin persisted during recovery, it was principally with the
      residual aggregates of actin in the cell body. Detachment of Na,K-ATPase from the
      cytoskeleton at 2-h ATP depletion was significantly less in Hsp27 cells compared
      with transfectant control G cells but not at 4-h ATP depletion. Detachment of
      ezrin from the cytoskeleton during ATP depletion was nearly complete and was not
      prevented in the Hsp27 cells. Protection of the Hsp27 cells was not attributable
      to preservation of cellular ATP levels. Hsp27 appears to have specific actions in
      renal epithelia subjected to energy depletion, including interacting with actin
      to preserve architecture in specific intracellular domains.

PMID- 12506143
TI  - Crystal retention capacity of cells in the human nephron: involvement of CD44 and
      its ligands hyaluronic acid and osteopontin in the transition of a crystal
      binding- into a nonadherent epithelium.
AB  - Nephrolithiasis requires formation of crystals followed by their retention and
      accumulation in the kidney. Crystal retention can be caused by the association of
      crystals with the epithelial cells lining the renal tubules. The present study
      investigated the interaction between calcium oxalate monohydrate (COM) crystals
      and primary cultures of human proximal (PTC) and distal tubular/collecting duct
      cells (DTC). Both PTC and DTC were susceptible to crystal binding during the
      first days post-seeding (4.9 +/- 0.8 micro g COM/cm2), but DTC lost this affinity
      when the cultures developed into confluent monolayers with functional tight
      junctions (0.05 +/- 0.02 micro g COM/cm2). Confocal microscopy demonstrated the
      expression of the transmembrane receptor protein CD44 and its ligands osteopontin
      (OPN) and hyaluronic acid (HA) at the apical membrane of proliferating tubular
      cells; at confluence, CD44 was expressed at the basolateral membrane and OPN and
      HA were no longer detectable. In addition, a particle exclusion technique
      revealed that proliferating cells were surrounded by HA-rich pericellular
      matrices or "cell coats" extending several microns from the cell surface.
      Disintegration of these coats with hyaluronidase significantly decreased the cell
      surface affinity for crystals. Furthermore, CD44, OPN, and HA were also expressed
      in vivo at the luminal side of tubular cells in damaged kidneys. These results
      suggest (1) that the intact distal tubular epithelium of the human kidney does
      not bind crystals, and (2) that crystal retention in the human kidney may depend
      on the expression of CD44-, OPN-, and-HA rich cell coats by damaged distal
      tubular epithelium.

PMID- 12506144
TI  - Selective regulation of ICAM-1 and RANTES gene expression after ICAM-1 ligation
      on human renal fibroblasts.
AB  - Leukocyte infiltration of the cortico-interstitium is characteristic of many
      forms of progressive renal disease. The principal adhesion molecule expressed on
      resident interstitial cells and recognized by leukocytes is intercellular
      adhesion molecule-1 (ICAM-1). ICAM-1 is an inducible transmembrane receptor,
      which forms the counter-receptor for the leukocyte beta 2 integrins. ICAM-1
      dependent binding induces the synthesis of the chemokine RANTES and of ICAM-1
      itself. This study examines some of the signaling pathways involved in this
      induction. After ICAM-1 cross-linking on fibroblasts, the mRNA and protein for
      both RANTES and ICAM-1 were induced. This induction was calcium-dependent and
      inhibited by BAPTA-AM. The p38, ERK1, and ERK2 MAP kinases were activated in a
      [Ca2+]i-dependent manner, with a maximum phosphorylation at approximately 3 min
      after cross-linking. Through the use of selective inhibitors of p38 MAP kinase
      (SB203580) or MEKK (PD98059), p38 but not ERK activation was shown to be
      essential for the induction of ICAM-1. Neither was involved in RANTES activation,
      however. These mechanisms differed from those initiated by TNF-alpha, which were
      not [Ca2+]i-dependent. Electrophoretic mobility shift analysis demonstrated a
      time-dependent induction of both AP-1 and NF-kappaB binding activity in nuclear
      extracts, maximal at approximately 15 min after ICAM-1 cross-linking. Only AP-1
      activation, however, was calcium-dependent, suggesting the central involvement of
      this transcription factor in ICAM-1 and RANTES induction after the ligation of
      ICAM-1. This study suggests an independent mechanism of inflammatory
      amplification, which may be characteristic of a persistent leukocytic involvement
      in areas of chronic inflammation rather than in cytokine-induced acute
      inflammation.

PMID- 12506145
TI  - P53 mediates the apoptotic response to GTP depletion after renal ischemia
      reperfusion: protective role of a p53 inhibitor.
AB  - Ischemic injury to the kidney is characterized in part by nucleotide depletion
      and tubular cell death in the form of necrosis or apoptosis. GTP depletion was
      recently identified as an important inducer of apoptosis during chemical anoxia
      in vitro and ischemic injury in vivo. It has also been shown that GTP salvage
      with guanosine prevented apoptosis and protected function. This study
      investigates the role of p53 in mediating the apoptotic response to GTP
      depletion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30
      min followed by reperfusion. p53 protein levels increased significantly in the
      medulla over 24 h post-ischemia. The provision of guanosine inhibited the
      increase in p53. Pifithrin-alpha, a specific inhibitor of p53, mimicked the
      effects of guanosine. It had no effect on necrosis, yet it prevented apoptosis
      and protected renal function. Pifithrin-alpha was protective when given up to 14
      h after the ischemic insult. The effects of pifithrin-alpha on p53 included
      inhibition of transcriptional activation of downstream p53 targets like p21 and
      Bax and inhibition of p53 translocation to the mitochondria. Similar results were
      obtained in cultured renal tubular cells. It is concluded that p53 is an
      important mediator of apoptosis during states of GTP depletion. Inhibitors of p53
      should be considered in the treatment of ischemic renal injury.

PMID- 12506146
TI  - Osteopontin is a critical inhibitor of calcium oxalate crystal formation and
      retention in renal tubules.
AB  - Calcium nephrolithiasis is the most common form of renal stone disease, with
      calcium oxalate (CaOx) being the predominant constituent of renal stones. Current
      in vitro evidence implicates osteopontin (OPN) as one of several macromolecular
      inhibitors of urinary crystallization with potentially important actions at
      several stages of CaOx crystal formation and retention. To determine the
      importance of OPN in vivo, hyperoxaluria was induced in mice targeted for the
      deletion of the OPN gene together with wild-type control mice. Both groups were
      given 1% ethylene glycol, an oxalate precursor, in their drinking water for up to
      4 wk. At 4 wk, OPN-deficient mice demonstrated significant intratubular deposits
      of CaOx crystals, whereas wild-type mice were completely unaffected. Retained
      crystals in tissue sections were positively identified as CaOx monohydrate by
      both polarized optical microscopy and x-ray powder diffraction analysis.
      Furthermore, hyperoxaluria in the OPN wild-type mice was associated with a
      significant 2- to 4-fold upregulation of renal OPN expression by
      immunocytochemistry, lending further support to a renoprotective role for OPN.
      These data indicate that OPN plays a critical renoprotective role in vivo as an
      inhibitor of CaOx crystal formation and retention in renal tubules.

PMID- 12506147
TI  - Effects of thyroparathyroidectomy, exogenous calcium, and short-term calcitriol
      therapy on the growth plate in renal failure.
AB  - Several factors have been implicated in the development of adynamic bone,
      including the use of calcium-containing phosphate binding agents, aggressive
      calcitriol therapy, and parathyroidectomy. To evaluate the effects of these
      interventions on the growth plate, weanling rats underwent sham nephrectomy
      (Control, n = 10) and 5/6 nephrectomy (Nx). In the nephrectomized group, animals
      underwent (a) thyroparathyroidectomy (Nx-TPTX, n = 7), (b) received exogenous
      calcium (Nx-Calcium, n = 10), (c) received short-term calcitriol therapy (Nx-D, n
      = 10), or (d) nephrectomized control (Nx-Control, n = 10). Higher serum calcium
      and lower PTH levels were demonstrated in Nx-Calcium and Nx-D animals. A decline
      in growth was demonstrated in Nx-Calcium and Nx-TPTX accompanied by shorter
      tibial lengths. The width of the growth plate was wider in Nx-Calcium animals due
      to an increase in the width of the hypertrophic zone and a decrease in the
      proliferative zone; these changes were accompanied by an impairment of
      chondroclastic resorption, lower gelatinase B/MMP-9 activity, decline in insulin
      like growth factor-I (IGF-I) receptor, and lower histone-4 mRNA expression. Such
      findings in the growth plate, may partially contribute to the diminution of
      growth in these animals. Although growth was impaired in the Nx-TPTX animals,
      there were no significant changes demonstrated in the growth plate cartilage.
      Histone-4 transcripts, IGF-I receptor expression, and histochemical staining for
      chondroclasts were decreased in Nx-D animals. Thus, treatments used in the
      management of secondary hyperparathyroidism in renal failure have diverse effects
      on the growth plate of the young skeleton, and concurrent use of these
      interventions needs further evaluation.

PMID- 12506148
TI  - Cardiac valve calcification as an important predictor for all-cause mortality and
      cardiovascular mortality in long-term peritoneal dialysis patients: a prospective
      study.
AB  - Calcification complications are frequent among long-term dialysis patients.
      However, the prognostic implication of cardiac valve calcification in this
      population is not known. This study aimed to determine if cardiac valve
      calcification predicts mortality in long-term dialysis patients. Baseline
      echocardiography was performed in 192 patients (mean +/- SD age, 55 +/- 12 yr) on
      continuous ambulatory peritoneal dialysis (mean +/- SD duration of dialysis, 39
      +/- 31 mo) to screen for calcification of the aortic valve, mitral valve, or
      both. Valvular calcification was present in 62 patients. During the mean follow
      up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes)
      were observed. Overall 1-yr survival was 70% and 93% for patients with and
      without valvular calcification (P < 0.0001, log-rank test). Cardiovascular
      mortality was 22% and 3% for patients with and without valvular calcification (P
      < 0.0001). Multivariable Cox regression analysis showed that cardiac valve
      calcification was predictive of an increased all-cause mortality (hazard ratio
      [HR], 2.50; 95% CI, 1.32 to 4.76; P = 0.005) and cardiovascular death (HR 5.39;
      95% CI, 2.16 to 13.48; P = 0.0003) independent of age, male gender, dialysis
      duration, C-reactive protein, diabetes, and atherosclerotic vascular disease.
      Eighty-nine percent of patients with both valvular calcification and
      atherosclerotic vascular disease, 23% of patients with valvular calcification
      only, 21% of patients with atherosclerotic vascular disease only, and 13% of
      patients with neither complication died at 1-yr (P < 0.0005). The cardiovascular
      death rate was 85% for patients with both complications, 13% for patients with
      valvular calcification only, 14% for patients with atherosclerotic vascular
      disease only, and 5% for those with neither complication (P < 0.0005). The number
      of calcified valves was associated with all-cause mortality (P < 0.0005) and
      cardiovascular death (P < 0.0005). One-year all-cause mortality was 57% for
      patients with both aortic and mitral valves calcified, 40% for those with either
      valve calcified, and 15% for those with neither valve calcified. In conclusion,
      cardiac valve calcification is a powerful predictor for mortality and
      cardiovascular deaths in long-term dialysis patients. Valvular calcification by
      itself has similar prognostic importance as the presence of atherosclerotic
      vascular disease. Its coexistence with other atherosclerotic complications
      indicates more severe disease and has the worst outcome.

PMID- 12506149
TI  - Hemodialysis infection prevention with polysporin ointment.
AB  - Hemodialysis patients in whom permanent vascular access cannot be achieved are
      dependent on a central venous catheter. In such patients, catheter-related
      infections are a common and serious complication. This study was a randomized
      clinical trial to determine if topical Polysporin Triple antibiotic ointment
      applied to the central venous catheter insertion site could reduce the incidence
      of catheter-related infections. A total of 169 patients receiving hemodialysis
      through a central venous catheter were randomized to receive Polysporin Triple or
      placebo using a double-blind study design. In the 6-mo study period, infections
      were observed in more patients in the placebo group than in the Polysporin Triple
      group (34 versus 12%; relative risk, 0.35; 95% CI, 0.18 to 0.68; P = 0.0013). The
      number of infections per 1000 catheter days (4.10 versus 1.02; P < 0.0001) and
      the number of bacteremias per 1000 catheter days (2.48 versus 0.63; P = 0.0004)
      were also greater in the placebo group. Within the 6-mo study period, there were
      13 deaths in the placebo group as compared with 3 deaths in the Polysporin Triple
      group (P = 0.0041). When all available follow-up information was included, the
      difference in survival remained significant (19 versus 9 deaths; P = 0.0027).
      Within the first 6 mo, infections were observed in 7 of the 13 placebo subjects
      who died (54%) as compared with no infections in the three Polysporin Triple
      subjects who died. The prophylactic application of topical Polysporin Triple
      antibiotic ointment to the central venous catheter insertion site reduced the
      rate of infections and was associated with improved survival in hemodialysis
      patients.

PMID- 12506150
TI  - Survival advantage for adult Hispanic hemodialysis patients? Findings from the
      end-stage renal disease clinical performance measures project.
AB  - One-year follow-up mortality in Hispanic and non-Hispanic patients and its
      association with intermediate outcomes of dialytic care were examined utilizing
      the Center for Medicare & Medicaid Services' (CMS) ESRD Clinical Performance
      Measures (CPM) Project and administrative data. Demographic and clinical
      information was collected on a national random sample of adult in-center
      hemodialysis (HD) patients for the period of October through December, 1998.
      Patients were categorized as Hispanic, non-Hispanic White, or non-Hispanic Black.
      Of 8336 patients 994 (12%) were identified as Hispanic, 3618 (43%) as non
      Hispanic White, and 3111 (37%) as non-Hispanic Black. The adjusted 12-mo
      mortality risk (99% CI) for Hispanics was 0.76 (0.60 to 0.96; P < 0.01) and for
      non-Hispanic Blacks 0.66 (0.56 to 0.78, P < 0.001) compared with non-Hispanic
      Whites (referent). Similar 12-mo mortality risks were noted in the groups with
      diabetes mellitus or hypertension as the causes of ESRD and among patients > or =
      65 yr. After controlling for demographic and geographic variables, Hispanics
      compared with the referent group, non-Hispanic Whites, were more likely to have a
      mean serum albumin > or = 4.0/3.7 g/dL (BCG/BCP) (1.5 [1.2 to 1.7]; P < 0.001)
      and as likely to have a mean Kt/V > or = 1.2, mean hemoglobin > or = 11 g/dL, and
      an arteriovenous fistula as their vascular access. These data suggest that adult
      Hispanic HD patients have a 12-mo survival intermediate to non-Hispanic Blacks
      and non-Hispanic Whites and experience equivalent or better intermediate outcomes
      of dialytic care compared with non-Hispanic Whites.

PMID- 12506151
TI  - Kidney transplantation in the elderly: a decision analysis.
AB  - Transplantation offers superior life expectancy and quality of life compared with
      dialysis in young patients with end-stage renal failure. However, the initial
      risks of mortality and morbidity are high. This study used a decision analysis
      model to evaluate the costs and benefits of kidney transplantation versus
      continued dialysis for older patients with renal failure. A decision analytic
      model comparing cadaveric renal transplantation to continued hemodialysis
      treatment was developed. The base case considered a theoretical cohort of
      patients aged 65 yr without known comorbidity or contraindications to
      transplantation who would have to wait 2 yr for a cadaveric transplant. Separate
      models were constructed for patients with diabetes or cardiovascular disease and
      for patients receiving an organ after a variety of wait-list times. Probability,
      utility, and survival data were obtained from published reports and renal
      registries. For 65-yr-old patients, quality-adjusted life expectancy increased by
      1.1 quality-adjusted life years (QALY) at an incremental cost of $67,778 per
      QALY. Assuming a 2-yr wait-listed time, transplantation remained economically
      attractive for 70-yr-old patients (incremental cost effectiveness [ICE], $79,359
      per QALY) but was less economically attractive for those over 75 yr of age (ICE,
      $99,553) or for 70-yr-olds with either cardiovascular disease or diabetes (ICE,
      $126,751 and $161,090 per QALY, respectively). The analytic results were
      sensitive only to the time spent waiting for the graft. The cost-effectiveness
      reduced such that the costs associated with one QALY were in excess of
      $100,000/yr when the probability of a complication was > or = 50% per 3-mo cycle
      and when the utility of transplantation fell below 0.62. If available within a
      timely period, transplantation may offer substantial clinical benefits to older
      patients at a reasonable financial cost. Prolonged waiting times dramatically
      decrease the clinical benefits and economic attractiveness of transplantation,
      suggesting that living donor transplantation may be of particular benefit in this
      population.

PMID- 12506152
TI  - Cancers of the kidney and urinary tract in patients on dialysis for end-stage
      renal disease: analysis of data from the United States, Europe, and Australia and
      New Zealand.
AB  - Patients on maintenance dialysis have increased risk for cancer, especially in
      the kidney and urinary tract. In a retrospective cohort of 831,804 patients
      starting dialysis during 1980 to 1994 in the United States, Europe, or Australia
      and New Zealand, standardized incidence ratios (SIR) with 95% confidence
      intervals (CI) were calculated for kidney and bladder cancers. Risks for cancers
      of the kidney (SIR 3.6; CI 3.5 to 3.8) and bladder (SIR 1.5; CI 1.4 to 1.6) were
      increased, relatively more in younger than older patients and more in female
      patients (kidney: SIR 4.6, CI 4.3 to 4.9; bladder: SIR 2.7, CI 2.4 to 2.9) than
      male patients (kidney: SIR 3.2, CI 3.0 to 3.4; bladder: SIR 1.3, CI 1.2 to 1.3).
      SIR for kidney cancer were raised in all categories of primary renal disease, and
      for bladder cancer in all but diabetes and familial, hereditary diseases. Notably
      high SIR occurred in toxic nephropathies (chiefly analgesic nephropathy) and
      miscellaneous conditions (a category that includes Balkan nephropathy), the
      excess of kidney cancer in these conditions being urothelial in origin. SIR for
      kidney cancer rose significantly, and those for bladder cancer fell (not reaching
      significance) with time on dialysis. There was no association with type of
      dialysis. The pattern of increased risk for renal parenchymal cancer in dialysis
      patients is consistent with causation through acquired renal cystic disease and
      of urothelial cancers of the kidney and bladder with the carcinogenic effects of
      certain primary renal diseases.

PMID- 12506153
TI  - Kidney allograft and patient survival in type I diabetic recipients of cadaveric
      kidney alone versus simultaneous pancreas kidney transplants: a multivariate
      analysis of the UNOS database.
AB  - Simultaneous pancreas-kidney transplant (SPK) is now a common treatment for
      insulin-dependent diabetic patients with end-stage renal disease. Renal graft
      survival rates after SPK have been less well studied. This study compared the
      kidney survival results for 3642 SPK and 2374 cadaveric renal transplants (CRT)
      in type I diabetic patients at 112 US transplant centers reported to UNOS during
      1994 through 1997. The analysis included follow-up information through September
      2000. The kidney graft survival rates were significantly lower among recipients
      of CRT compared with SPK recipients (P < 0.001). Patients who received SPK were
      younger, less often sensitized, transplanted after shorter periods on dialysis,
      and less often black. The donors of SPK organs were younger, more often died from
      head trauma, were less often female, and more often black. SPK renal grafts were
      transplanted with a shorter cold ischemia time to more poorly HLA-matched
      recipients. After adjustment of these and other factors, whether a patient was
      recipient of CRT or SPK was not associated with increased risk of kidney graft
      failure or patient death. SPK recipients experienced half the rate of delayed
      kidney function (11% versus 23%) but nearly double the rate of rejections during
      the initial hospitalization (15% versus 9%) compared with CRT recipients. SPK was
      associated with better renal allograft survival compared with CRT, despite a
      higher rate of renal allograft rejection. This observation was explained by
      favorable donor and recipient factors in the SPK group. After controlling for
      these factors, SPK provided no protective or detrimental effect on short-term
      renal allograft or patient survival.

PMID- 12506154
TI  - Targeting of macrophage activity by adenovirus-mediated intragraft overexpression
      of TNFRp55-Ig, IL-12p40, and vIL-10 ameliorates adenovirus-mediated chronic graft
      injury, whereas stimulation of macrophages by overexpression of IFN-gamma
      accelerates chronic graft injury in a rat renal allograft model.
AB  - Adenovirus (Ad)-mediated gene transfer of immunoregulatory molecules prevents
      acute allograft rejection. It is here analyzed for the first time whether this
      approach may prevent the development of chronic renal allograft injury in rats.
      Renal allografts (F344-->Lewis rat) were ex vivo transduced in group I with
      control Ad-construct, group II with three different therapeutic Ad-constructs
      expressing the immunoregulatory molecules vIL-10, TNFRp55-Ig, and IL-12p40, and
      group III with AdIFN-gamma. Group IV served as untreated controls. Control grafts
      (IV) showed increasing proteinuria during the 24-wk follow-up. Chronic graft
      injury was accelerated by Ad-control (I) and even more by AdIFN-gamma (III). All
      rats carrying the AdIFN-gamma-transduced grafts died within 12 to 13 wk by
      advanced chronic renal failure associated with strong immune cell infiltration
      and immune gene expression. By contrast, the Ad-therapy group II showed less
      inflammation and improved graft histology and function if compared with the
      groups I and III. Moreover, significantly less infiltrating ED-1(+) macrophages
      and an improved histologic score even if compared with untreated controls (IV)
      was observed. However, after disappearance of therapeutic gene expression, group
      II showed increasing proteinuria probably as result of late T cell activation to
      the Ad-encoded proteins. Ex vivo transduction of allografts with Ad-control or
      even more AdIFN-gamma expression promotes intragraft inflammation and chronic
      graft injury. Targeting macrophage activation by a cocktail of therapeutic genes
      improved the results. These data support the pathogenetic role of cytokines in
      chronic graft injury; however, they also show the limitations of the Ad-mediated
      gene transfer.

PMID- 12506155
TI  - Heightened peripheral blood lymphocyte CD69 expression is neither sensitive nor
      specific as a noninvasive diagnostic test for renal allograft rejection.
AB  - It has been reported that acute allograft rejection is associated with heightened
      expression of the peripheral blood lymphocyte (PBL) early activation marker CD69
      and that this may serve as a potential biomarker of rejection. This study sought
      to determine whether PBL CD69 expression correlates with both acute clinical and
      subclinical renal allograft rejection as well as clinically inapparent
      cytomegalovirus (CMV) infection. Flow cytometric determination of PBL CD69
      expression was performed at the time of clinical and protocol biopsies (n = 131)
      in 45 renal transplant recipients. Nineteen patients also underwent weekly
      monitoring of PBL CD69 expression for the initial 15 wk after transplantation.
      Simultaneous screening for CMV viremia was performed with a semiquantitative PCR
      assay. No differences were seen in either CD4+ or CD8+ lymphocyte CD69 expression
      between the biopsy diagnoses. CMV viremia however, independent of rejection, was
      associated with greater CD69 expression on CD8+ lymphocytes (17.8 +/- 10.4%
      versus 9.6 +/- 4.8%; P < 0.0001) but not CD4+ lymphocytes. No individuals
      experienced clinical CMV disease. Weekly monitoring of PBL CD69 expression did
      not change coincident with the diagnosis of rejection; however, CMV viremia
      coincided with a substantial rise in the proportion of CD8+69+ lymphocytes in a
      number of individuals. Thus, PBL CD69 expression is neither sensitive nor
      specific for the noninvasive diagnosis of renal allograft rejection. Furthermore,
      clinically inapparent CMV viremia is associated with heightened expression of
      this activation marker on CD8+ lymphocytes. This latter finding suggests that
      clinically inapparent CMV viremia may be a potential confounder for biomarkers of
      rejection that examine peripheral blood lymphocytes.

PMID- 12506156
TI  - Outcome of kidney transplantation in patients with inherited thrombophilia: data
      of a prospective study.
AB  - Inherited prothrombotic risk factors predispose patients to thromboembolic
      events. In kidney transplant recipients, thrombophilia may manifest itself with
      venous thrombosis, microvascular occlusion, or acute rejection with major
      consequences for allograft survival. This is a prospective study on 165 renal
      allograft recipients to evaluate the contribution of genetic thrombophilic risk
      factors to transplant outcome. Besides antithrombin, protein C, and protein S
      deficiencies, none of which was found in our patient group, factor V G1691A (FV
      G1691A), prothrombin G20210A (PT G20210A) mutations, and
      methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms were
      studied. The primary endpoint of the study was occurrence of an acute rejection
      within the first 90 d and transplant loss within 1 yr. Heterozygous FV G1691A and
      PT G20210A mutations and the MTHFR T677T variant were significantly associated
      with acute rejections with rejection rates of 68%, 67%, and 71%, respectively, as
      compared with 35% in patients not carrying these genotypes. Many rejections that
      were histologically proven were acute vascular ones. Transplant loss was
      significantly associated exclusively with the PT G20210A group (50% 1-yr graft
      survival; odds ratio, 10.0; 95% confidence interval, 1.8 to 56.1). PT G20210A
      patients exerted the highest prothrombotic activity pretransplant, as determined
      by prothrombin 1.2 fragments (PT F1.2), which may be the background for minor
      outcome. In conclusion, common prothrombotic mutations are significantly
      associated with acute rejections, especially vascular rejections, and for PT
      G20210A also with early transplant failure. Screening for hypercoagulable states
      pretransplant is recommended to intensify anticoagulatory treatment
      posttransplant.

PMID- 12506157
TI  - Disorders of renal tubular phosphate transport.

PMID- 12506158
TI  - Recent advances in molecular genetics of hereditary magnesium-losing disorders.
AB  - Recent advances in molecular genetics in hereditary hypomagnesemia substantiated
      the role of a variety of genes and their encoded proteins in human magnesium
      transport mechanisms. This knowledge on underlying genetic defects helps to
      distinguish different clinical subtypes and gives first insight into molecular
      components involved in magnesium transport. By mutation analysis and functional
      protein studies, novel pathophysiologic aspects were elucidated. For some of
      these disorders, transgenic animal models were generated to study genotype
      phenotype relations and disease pathology. This review will discuss genetic and
      clinical aspects of familial disorders associated with magnesium wasting and
      focuses on the recent progress that has been made in molecular genetics. Besides
      isolated renal forms of hereditary hypomagnesemia, the following disorders will
      also be presented: familial hypomagnesemia with hypercalciuria and
      nephrocalcinosis, hypomagnesemia with secondary hypocalcemia, Ca2+/Mg2+-sensing
      receptor-associated disorders, and disorders associated with renal salt-wasting
      and hypokalemic metabolic alkalosis, comprising the Gitelman syndrome and the
      Bartter-like syndromes.

PMID- 12506159
TI  - Signaling: focus on Rho in renal disease.

PMID- 12506160
TI  - Transitioning to therapy in ischemic acute renal failure.

PMID- 12506161
TI  - Something old, something few, something subjective, something deja vu.

PMID- 12506162
TI  - The ups and downs of the estrogen receptor.

PMID- 12506163
TI  - Prolonged single-agent versus combination chemotherapy in indolent follicular
      lymphomas: a study of the cancer and leukemia group B.
AB  - PURPOSE: The array of options for the initial management of follicular small
      cleaved lymphoma (FSCL) and follicular mixed lymphoma (FML) ranges from little or
      no therapy to the use of intensive combinations of drugs. The Cancer and Leukemia
      Group B (CALGB) compared two contrasting approaches: a single agent, and
      combination chemotherapy capable of curing diffuse aggressive lymphomas. PATIENTS
      AND METHODS: A total of 228 patients with stage III or IV FSCL or FML were
      randomized to cyclophosphamide or the combination of cyclophosphamide,
      doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B). Treatment was
      continued in responders for 2 years beyond maximal response. The primary end
      point was survival in the most common subtype, FSCL. RESULTS: Ninety-one percent
      of all patients responded; complete responses were seen in 66% of those treated
      with cyclophosphamide and in 60% treated with CHOP-B (P =.36). At 10 years with
      either cyclophosphamide or CHOP-B, respectively, overall time to failure (25%
      failure free v 33%; P =.107) and survival (44% alive v 46%; P =.79) were similar
      by treatment. Outcomes in FSCL also were similar. In 46 patients with FML, at 10
      years the combination was associated with better failure-free (9% v 48%; P =.005)
      and overall (25% v 61%; P =.024) survival. Acute toxic effects were more common
      with combination chemotherapy. Second malignancies, which might be attributed to
      treatment, were seen with both approaches. CONCLUSION: There is no advantage to
      the initial use of the relatively intensive combination, CHOP-B, for patients
      with FSCL compared with the less toxic single agent, cyclophosphamide. However,
      in an unplanned subgroup analysis, patients with FML who received the combination
      experienced improved disease control and survival.

PMID- 12506164
TI  - Thalidomide alone or with dexamethasone for previously untreated multiple
      myeloma.
AB  - PURPOSE: To evaluate the activity of thalidomide in patients with asymptomatic
      multiple myeloma and of thalidomide-dexamethasone in patients with previously
      untreated symptomatic myeloma. PATIENTS AND METHODS: Twenty-eight patients with
      previously untreated asymptomatic myeloma were treated with thalidomide 100 to
      200 mg orally (PO) at bedtime (qhs) with serial increments of 50 to 100 mg at
      weekly intervals, as tolerated to a maximum of 600 mg PO qhs. Forty consecutive
      previously untreated patients with symptomatic myeloma were also treated as above
      (maximum dose 400 mg) and received dexamethasone 20 mg/m(2) for 4 days beginning
      on days 1, 9, and 17; the second and third cycles of repeated dexamethasone were
      begun on day 30. Both groups of patients were treated for at least 3 months.
      RESULTS: The response rate was 36% for patients treated with thalidomide alone
      and 72% for patients treated with thalidomide-dexamethasone, the latter including
      complete remission in 16% of patients. The median time to remission was 4.2
      months with thalidomide alone and 0.7 months with thalidomide-dexamethasone.
      Grade 3 toxicity included infections (nine patients) and thrombotic/embolic
      events (seven patients). Five deaths have occurred as a result of multiple
      myeloma (two patients), infection (one patient), unknown cause (one patient), and
      a possible thromboembolic event (one patient). CONCLUSION: Thalidomide alone was
      effective in patients with newly diagnosed myeloma. The combination with
      dexamethasone induced a high frequency of response, rapid onset of remission, and
      low incidence of serious irreversible toxicity. These observations support
      further studies of this promising combination for patients with newly diagnosed
      multiple myeloma.

PMID- 12506165
TI  - Patterns of outcome and prognostic factors in primary large-cell lymphoma of the
      testis in a survey by the International Extranodal Lymphoma Study Group.
AB  - PURPOSE: To determine clinical features and patterns of outcome of primary
      testicular diffuse large B-cell lymphomas (DLCL). PATIENTS AND METHODS: A
      retrospective international survey of 373 patients with primary testicular DLCL.
      RESULTS: Most patients presented with localized disease (stage I to II), and the
      median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based
      chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal
      chemotherapy was given to 68 patients (18%); 133 patients (36%) received
      prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and
      median progression-free survival was 4 years. The survival curves showed no clear
      evidence of a substantial proportion of cured patients. A favorable international
      prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and
      prophylactic scrotal radiotherapy were significantly associated with longer
      survival at multivariate analysis. However, even for patients with stage I
      disease and good-risk IPI, the outcome seems worse than what was reported for
      DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had
      relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were
      detected in 56 patients (15%) up to 10 years after presentation. A continuous
      risk of recurrence in the contralateral testis was seen in patients not receiving
      scrotal radiotherapy. CONCLUSION: Testicular DLCL is characterized by a
      particularly high risk of extranodal relapse even in cases with localized disease
      at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and
      contralateral testicular irradiation seem to improve the outcome. Their efficacy
      is under evaluation in a prospective clinical trial.

PMID- 12506166
TI  - Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998.
AB  - PURPOSE: Between 1987 and 1998, breast cancer incidence rates rose 0.5%/yr in the
      United States. A question of potential etiologic and clinical importance is
      whether the hormone receptor status of breast tumors is also changing over time.
      This is because hormone receptor status may reflect different etiologic pathways
      and is useful in predicting response to adjuvant therapy and prognosis. METHODS:
      Age-adjusted, age-specific breast cancer incidence rates by estrogen receptor
      (ER) and progesterone receptor (PR) status from 1992 to 1998 were obtained and
      compared from 11 population-based cancer registries in the United States that
      participate in the National Cancer Institute's Surveillance, Epidemiology, and
      End Results (SEER) Program. RESULTS: From 1992 to 1998, the overall proportion of
      breast cancers that were ER-positive and PR-positive increased from 75.4% to
      77.5% (P =.0002) and from 65.0% to 67.7% (P <.0001), respectively, continuing
      trends observed before 1992. These increases were limited to women 40 to 69 years
      of age. The proportions of ER-positive/PR-positive tumors increased from 56.7% to
      62.3% (P =.0010) among 40- to 49-year-olds, from 58.0% to 63.2% (P =.0002) among
      50- to 59-year-olds, and from 63.2% to 67.9% (P =.0020) among 60- to 69-year
      olds. CONCLUSION: From 1992 to 1998, the proportion of tumors that are hormone
      receptor-positive rose as the proportion of hormone receptor-negative tumors
      declined. Because the incidence rates of hormone receptor-negative tumors
      remained fairly constant over these years, the overall rise in breast cancer
      incidence rates in the United States seems to be primarily a result of the
      increase in the incidence of hormone receptor-positive tumors. Hormonal factors
      may account for this trend.

PMID- 12506167
TI  - Phase II study of oral vinorelbine in first-line advanced breast cancer
      chemotherapy.
AB  - PURPOSE: A phase II trial was performed to evaluate the efficacy, tolerance, and
      pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB;
      Pierre Fabre Medicament, Boulogne, France) was given as first-line chemotherapy
      for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS:
      Sixty-four patients were entered to receive oral NVB on a weekly basis for a
      total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at
      60 mg/m(2) weekly for the first three administrations and was increased to 80
      mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or
      no more than one episode of grade 3 neutropenia. Patients with objective response
      or stable disease continued treatment up to a total of 12 weeks or more. RESULTS:
      Fifty-eight evaluable patients were included in our study. Four patients (6.9%)
      had complete responses, and 14 (24.1%) had partial responses, for an overall
      response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was
      17.4 weeks. Median overall survival is not yet reached. There were no treatment
      related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the
      patients, and 1.8% of administrations and associated clinical serious events in 4
      patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6%
      of the patients, respectively. Only one patient developed grade 3
      neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms
      revealed no significant alteration between baseline and weeks 8 and 16 in global
      quality of life. CONCLUSION: Oral NVB at this schedule is an effective and well
      tolerated agent in the treatment of ABC and offers a promising alternative to the
      intravenous route. Combination studies are ongoing.

PMID- 12506168
TI  - High prevalence of premalignant lesions in prophylactically removed breasts from
      women at hereditary risk for breast cancer.
AB  - PURPOSE: Women with a hereditary predisposition for breast cancer have an
      extremely high risk of developing invasive breast carcinoma, and many women
      consider prophylactic mastectomy to avoid this risk. The use of prophylactic
      mastectomy is still debated. Identification of frequent premalignant lesions in
      mastectomy specimens would support the preventive concept of prophylactic
      mastectomy. PATIENTS AND METHODS: We performed a prospective study of breast
      specimens from 67 women at extremely high genetic risk of breast cancer, with or
      without previous breast cancer, who were undergoing prophylactic mastectomy (66%
      were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by
      radiographic and macroscopic examination of 5-mm tissue slices, with subsequent
      histology of suspicious lesions and random samples from each quadrant of the
      breast and the nipple area. RESULTS: In 57% of the women, one or more different
      types of high-risk histopathologic lesions were present: 37% atypical lobular
      hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and
      15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one
      woman with ductal carcinoma-in-situ. None of these lesions was detected at
      palpation or mammography, which were performed before the mastectomy. The
      presence of high-risk lesions was independently related to age older than 40
      years (odds ratio, 6.6; P =.01) and to bilateral oophorectomy before prophylactic
      mastectomy (odds ratio, 0.2; P = 0.02). CONCLUSION: Many women at high risk of
      hereditary breast cancer develop high-risk histopathologic lesions, especially
      after the age of 40 years. Surveillance does not detect such high-risk
      histopathologic lesions.

PMID- 12506169
TI  - Preoperative therapy with trastuzumab and paclitaxel followed by sequential
      adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III
      breast cancer: a pilot study.
AB  - PURPOSE: Trastuzumab combined with chemotherapy improves outcomes for women with
      human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast
      cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel,
      followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in
      earlier stage breast cancer. PATIENTS AND METHODS: Patients with HER2-positive
      (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received
      preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with
      paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant
      doxorubicin and cyclophosphamide chemotherapy following definitive breast
      surgery. Clinical and pathologic response rates were determined after
      preoperative therapy. Left ventricular ejection fraction and circulating levels
      of HER2 extracellular domain were measured serially. RESULTS: Preoperative
      trastuzumab and paclitaxel achieved clinical response in 75% and complete
      pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more
      likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related
      noncardiac toxicity was encountered. Four patients developed grade 2
      cardiotoxicity (asymptomatic declines in left ventricular ejection fraction).
      Baseline HER2 extracellular domain was elevated in 24% of patients and declined
      with preoperative therapy. Immunohistochemical analyses of posttherapy tumor
      specimens indicated varying patterns of HER2 expression following trastuzumab
      based treatment. CONCLUSION: Preoperative trastuzumab and paclitaxel is active
      against HER2 overexpressing early-stage breast cancer and may be feasible as part
      of a sequential treatment program including anthracyclines. The observed changes
      in cardiac function merit further investigation. Correlative analyses of HER2
      status may facilitate understanding of tumor response and resistance to targeted
      therapy.

PMID- 12506170
TI  - Randomized phase III trial of fluorouracil alone versus fluorouracil plus
      cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable,
      advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205).
AB  - PURPOSE: To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with
      uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric
      cancer in a prospective, randomized, controlled trial. PATIENTS AND METHODS: A
      total of 280 patients with advanced gastric cancer were randomly allocated and
      analyzed for survival, response, and toxicity. The survival curves were compared
      between groups by log-rank test on an intent-to-treat basis. RESULTS: At the
      interim analysis, the UFTM arm showed a significantly inferior survival with
      higher incidences of hematologic toxic effects than did control arm FU alone, and
      the registration to UFTM was terminated. Both investigational regimens, FP and
      UFTM, had a significantly higher incidence of hematologic toxic effects than FU
      alone, although the effects were manageable. The overall response rates of the FU
      alone, FP, and UFTM arms were 11%, 34%, and 9%, respectively. The median
      progression-free survival was 1.9 months with FU alone, 3.9 months with FP, and
      2.4 months with UFTM, respectively. Although FP demonstrated a higher response
      rate (P <.001) and longer progression-free survival than did FU alone (P <.001),
      no differences in overall survival were observed between the arms. The median
      survival times and 1-year survival rates were 7.1 months and 28% with FU, 7.3
      months and 29% with FP, and 6.0 months and 16% with UFTM, respectively.
      CONCLUSION: Neither investigational regimen, FP nor UFTM, showed a survival
      advantage as compared with FU alone. FU alone will remain a reference arm in our
      future trial for advanced gastric cancer.

PMID- 12506171
TI  - Phase II, randomized trial comparing bevacizumab plus fluorouracil
      (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal
      cancer.
AB  - PURPOSE: This phase II trial investigated the safety and efficacy of two doses of
      bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus
      fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic
      colorectal cancer. PATIENTS AND METHODS: One hundred four previously untreated
      patients with measurable metastatic colorectal cancer were randomly assigned to
      one of the following three treatment groups: 36 to FU (500 mg/m(2))/LV (500
      mg/m(2)) alone, 35 to FU/LV + low-dose bevacizumab (5 mg/kg every 2 weeks), and
      33 to FU/LV + high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given
      weekly for the first 6 weeks of each 8-week cycle. RESULTS: Compared with the
      FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV
      resulted in higher response rates (control arm, 17%, 95% confidence interval
      [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95%
      CI, 12% to 43%), longer median time to disease progression (control arm, 5.2
      months, 95% CI, 3.5 to 5.6 months; low-dose arm, 9.0 months, 95% CI, 5.8 to 10.9
      months; high-dose arm, 7.2 months, 95% CI, 3.8 to 9.2 months), and longer median
      survival (control arm, 13.8 months; 95% CI, 9.1 to 23.0 months; low-dose arm,
      21.5 months, 95% CI, 17.3 to undetermined; high-dose arm, 16.1 months; 95% CI,
      11.0 to 20.7 months). After cross-over, two of 22 patients had a partial response
      to bevacizumab alone. Thrombosis was the most significant adverse event and was
      fatal in one patient. Hypertension, proteinuria, and epistaxis were other
      potential safety concerns. CONCLUSION: The encouraging results of this randomized
      trial support further study of bevacizumab 5 mg/kg plus chemotherapy as first
      line therapy for metastatic colorectal cancer.

PMID- 12506172
TI  - Combining capecitabine and gemcitabine in patients with advanced pancreatic
      carcinoma: a phase I/II trial.
AB  - PURPOSE: Preclinical studies indicate positive interactions between capecitabine,
      an oral fluorouracil precursor, and gemcitabine, the current standard treatment
      for advanced pancreatic carcinoma (APC). In this study, we investigated the
      addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS
      AND METHODS: This multicenter study included patients naive to chemotherapy who
      had histologically or cytologically confirmed, nonresectable or metastatic
      pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on
      days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally
      bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was
      defined as one dose level below the dose causing dose-limiting toxicity (DLT) in
      >or= one third of a cohort of six patients. We included an additional 15 patients
      at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of
      800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis.
      Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in
      this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27
      patients with measurable disease, we observed one complete and four partial
      remissions. In addition, significant drops (> 50% from baseline value) of the
      tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The
      combination of capecitabine and gemcitabine is well tolerated, with apparent
      efficacy in patients with APC. Therefore, it is currently being compared with
      gemcitabine monotherapy in a phase III study.

PMID- 12506173
TI  - Depression and psychological distress in patients during the year after curative
      resection of non-small-cell lung cancer.
AB  - PURPOSE: There have been few psychosocial studies of patients after curative
      resection of non-small-cell lung cancer (NSCLC). The purpose of this study was to
      clarify the clinical course of depression and psychological distress of such
      patients during the year after surgery and to identify predictors of their long
      term outcome. PATIENTS AND METHODS: A total of 212 patients completed assessments
      during a 12-month follow-up period after curative resection of NSCLC.
      Psychological measurements at 1, 3, and 12 months after surgery were conducted
      using the Structured Clinical Interview for Diagnostic and Statistical Manual of
      Mental Disorders (ed 3), Revised, and the Profiles of Mood States (POMS) scale.
      Univariate and multivariate analyses were used to identify predictors of
      psychological outcome according to these two methods of assessment. RESULTS: The
      prevalence of depression did not change during the year after curative resection
      (range, 4.7% to 8.0%). The total POMS score was also unaltered during the year
      after surgery: the anger-hostility (P <.001) and tension-anxiety subscale scores
      (P <.026) had increased at 12 months, but the vigor-activity subscale score had
      also increased (P <.001). All predictors of psychological outcome at 12 months
      included a depression episode after the diagnosis of lung cancer or at 1 month
      after surgery. Less-educated status was also a significant predictor of
      depression at 12 months. CONCLUSION: These results suggest the need for
      psychosocial support even after curative resection of NSCLC and indicate that an
      approach that includes repetitive perioperative assessment of depression and
      careful attention to less-educated patients might be of benefit to patients in
      ameliorating depression and psychological distress during the year after curative
      resection.

PMID- 12506174
TI  - Prognostic factors and clinical outcomes in children and adolescents with
      metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study
      IV.
AB  - PURPOSE: To identify risk factors associated with outcomes in children with
      metastatic rhabdomyosarcoma (RMS) treated on the fourth Intergroup
      Rhabdomyosarcoma Study (IRS-IV). PATIENTS AND METHODS: Patients with metastatic
      RMS were treated with one of two regimens that incorporated a window of either
      ifosfamide and etoposide (IE) with vincristine, dactinomycin, and
      cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points
      were failure-free survival (FFS) and overall survival (OS). Clinical factors
      including age, histology, sites of primary and metastatic disease, and number of
      sites of metastatic disease were correlated with those end points. RESULTS: One
      hundred twenty-seven patients were eligible for analysis. The estimated 3-year OS
      and FFS for all patients were 39% and 25%, respectively. By univariate analysis,
      3-year OS was significantly influenced by histology (47% for embryonal v 34% for
      all others, P =.026) and increasing number of metastatic sites (P =.028). By
      multivariate analysis, the presence of two or fewer metastatic sites was the only
      significant predictor (P =.007 and.006, respectively). The combination of
      embryonal histology with two or fewer metastatic sites identified a subgroup with
      3-year FFS of 40% and OS of 47%. CONCLUSION: Children with group IV RMS treated
      on the IRS-IV study had improved OS and FFS if they had two or fewer metastatic
      sites and embryonal histology. This favorable subset of patients has outcomes
      approaching those observed in selected patients with localized, nonmetastatic
      disease. Thus, these patients might not be appropriate candidates for regimens
      that include experimental agents with substantial toxicities or unproven
      antitumor activity.

PMID- 12506175
TI  - Increased risk of systemic relapses associated with bone marrow micrometastasis
      and circulating tumor cells in localized ewing tumor.
AB  - PURPOSE: The presence of metastasis is a major prognostic factor in Ewing tumor
      (ET). The relapse pattern of patients with localized tumors has long indicated
      that cases with disseminated ET cells escape detection at diagnosis. ET cells are
      characterized by specific gene fusions that can be detected with high sensitivity
      and specificity by reverse transcriptase polymerase chain reaction (RT-PCR).
      PATIENTS AND METHODS: RT-PCR targeting EWS-FLI-1 or EWS-ERG transcripts was used
      to search for occult tumor cells in peripheral blood (PB) and bone marrow (BM) at
      diagnosis in 172 patients with ET, and the prognostic significance of this
      parameter was assessed. RESULTS: As we suggested previously in a smaller series
      of patients, RT-PCR positivity of the BM was correlated with a high risk of
      adverse outcome in the overall study population (P =.007). More interestingly,
      among patients with otherwise localized tumors, BM micrometastasis also predicted
      significantly poorer disease-free survival rates (P =.043). The presence of
      circulating tumor cells (CTC) was more frequently observed in patients with large
      tumors (P =.006). CTC were associated with a poor outcome among patients with
      clinically localized disease (P =.045). Patients with clinically localized
      disease and peripheral occult tumor cells as evidenced by BM and/or PB RT-PCR
      positivity had axial or proximal tumors and experienced relapses at a systemic
      rather than at a local level. CONCLUSION: Patients with localized ET and BM
      micrometastasis or CTC are comparable to patients with metastases in terms of the
      localization of the primary tumor, outcome, and relapse pattern.

PMID- 12506176
TI  - An intergroup phase III comparison of standard radiation therapy and two
      schedules of concurrent chemoradiotherapy in patients with unresectable squamous
      cell head and neck cancer.
AB  - PURPOSE: The Head and Neck Intergroup conducted a phase III randomized trial to
      test the benefit of adding chemotherapy to radiation in patients with
      unresectable squamous cell head and neck cancer. PATIENTS AND METHODS: Eligible
      patients were randomly assigned between arm A (the control), single daily
      fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with
      concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split
      course of single daily fractionated radiation and three cycles of concurrent
      infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the
      first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was
      encouraged if possible after the second chemotherapy cycle on arm C and, if
      necessary, as salvage therapy on all three treatment arms. Survival data were
      compared between each experimental arm and the control arm using a one-sided log
      rank test. RESULTS: Between 1992 and 1999, 295 patients were entered on this
      trial. This did not meet the accrual goal of 362 patients and resulted in
      premature study closure. Grade 3 or worse toxicity occurred in 52% of patients
      enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77%
      enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year
      projected overall survival for patients enrolled in arm A is 23%, compared with
      37% for arm B (P =.014) and 27% for arm C (P = not significant). CONCLUSION: The
      addition of concurrent high-dose, single-agent cisplatin to conventional single
      daily fractionated radiation significantly improves survival, although it also
      increases toxicity. The loss of efficacy resulting from split-course radiation
      was not offset by either multiagent chemotherapy or the possibility of midcourse
      surgery.

PMID- 12506177
TI  - Prostate-specific antigen kinetics as a measure of the biologic effect of
      granulocyte-macrophage colony-stimulating factor in patients with serologic
      progression of prostate cancer.
AB  - PURPOSE: To determine the biologic effect of granulocyte-macrophage colony
      stimulating factor (sangramostim, GM-CSF; Immunex Corporation, Seattle, WA) as
      measured by prostate-specific antigen (PSA) kinetics in patients with serologic
      progression of prostate cancer after definitive local therapy. PATIENTS AND
      METHODS: Patients with prostate cancer who had undergone previous definitive
      surgical or radiation therapy with nonmetastatic, recurrent disease as manifested
      by a rising PSA between 0.4 ng/mL and 6.0 ng/mL were enrolled on this phase II
      trial. Patients received 250 micro g/m(2)/day of subcutaneous GM-CSF on days 1
      through 14 of a 28-day cycle. PSA was measured at day 1 of each cycle. RESULTS:
      Thirty patients with serologic progression of prostate cancer were treated. The
      median pretreatment PSA was 2.9 ng/mL. Of the 29 evaluable patients, three
      patients (10%; 95% confidence interval, 2% to 27%) achieved a 50% reduction in
      PSA. For the patients (n = 26) in whom the on-treatment PSA doubling time could
      be calculated, the median PSA doubling time increased from 8.4 months to 15
      months (P =.001), and the median slope of the PSA versus time curve decreased
      with treatment (P =.004). Therapy was well tolerated by all patients, with an
      average treatment duration of 16.5 cycles (range, 5 to 33). CONCLUSION: GM-CSF
      has a biologic effect in patients with serologic progression of prostate cancer
      after definitive local therapy, as measured by PSA declines and modulation of PSA
      kinetics.

PMID- 12506178
TI  - Differential expression of S100A2 and S100A4 during progression of human prostate
      adenocarcinoma.
AB  - PURPOSE: To establish the clinical significance of calcium binding proteins
      S100A2 and S100A4 during progression of human prostate adenocarcinoma. PATIENTS
      AND METHODS: Expression pattern of S100A2 and S100A4 was determined in normal
      human prostate epithelial cells (NHPE); virally transformed prostate epithelial
      cells (PZ-HPV-7); several human prostate carcinoma cells (22Rv1, DU145, LNCaP,
      and PC3); tissue samples obtained during transuretheral prostatic resection from
      patients with benign prostate hyperplasia (BPH), prostatitis, and adenocarcinoma;
      and paraffin-embedded sections from pair-matched benign and cancer specimens of
      different tumor grade. RESULTS: High constitutive protein expression of S100A2
      was observed in NHPE and PZ-HPV-7 cells, whereas its complete absence was
      observed in 22Rv1, DU145, LNCaP, and PC3 cells. Tissue samples of BPH and
      prostatitis exhibited higher mRNA and protein levels of S100A2 than low-grade
      cancer (Gleason score <or= 6), whereas a complete loss was observed in high-grade
      cancer specimens (Gleason score > 6). Immunohistochemical analysis further
      confirmed high levels of S100A2 in benign tissues and a progressive loss with
      increasing tumor grade. The protein level of S100A4 was significantly higher in
      all carcinoma cells compared with NHPE and PZ-HPV-7 cells. The mRNA and protein
      level of S100A4 was significantly higher in high-grade cancer specimens compared
      with BPH, prostatitis, and low-grade cancer. The high levels of S100A4 observed
      in cancer tissue correlated with increasing tumor grade. CONCLUSION: Loss of
      S100A2 and increased expression of S100A4 may be an important event during
      progression of prostate cancer in humans.

PMID- 12506179
TI  - Update on late relapse of germ cell tumor: a clinical and molecular analysis.
AB  - PURPOSE: Analysis of patients with late relapse (LR) of germ cell tumor (GCT)
      with reports on clinical characteristics, outcomes, and molecular and cytogenetic
      features. PATIENTS AND METHODS: Eighty-three patients evaluated at Indiana
      University from 1993 through 2000 for relapse of GCT more than 2 years from
      initial therapy were reviewed. Available specimens were investigated for
      expression of the transcription regulator FoxD3 and apurinic/apyrimidinic
      endonuclease and the presence of chromosome 12 abnormalities. RESULTS: Median
      interval from initial presentation to LR was 85 months. Forty-three of 49 LR
      patients who underwent surgery were rendered disease free (NED), and 20 (46.5%)
      remain continuously NED. Thirty-two patients received chemotherapy, but only six
      (18.8%) obtained a complete remission. Five of these patients remain continuously
      NED after chemotherapy alone, including three who were chemotherapy naive.
      Eighteen of these 32 patients were successfully rendered NED by postchemotherapy
      surgery, and 12 remain continuously NED. Two patients continue on observation
      with no treatment for their LR. Overall, 69 of the 81 treated patients (85.2%)
      ultimately achieved an NED state, and 38 (46.9%) remain continuously NED with
      median follow-up from LR therapy of 24.5 months (range, 1 to 83 months), whereas
      nine other patients are currently NED after therapy for subsequent relapses.
      Because of the small numbers of specimens tested, we were unable to draw any
      definitive conclusions from the molecular and cytogenetic analyses. CONCLUSION:
      GCT patients require lifetime follow-up. At the time of LR, surgical resection
      alone remains our preferred therapy.

PMID- 12506180
TI  - Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent
      prostate cancer.
AB  - PURPOSE: To determine the safety and efficacy of weekly high-dose oral calcitriol
      (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere,
      Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen
      independent prostate cancer (AIPC). PATIENTS AND METHODS: Thirty-seven patients
      were treated with oral calcitriol (0.5 micro g/kg) on day 1 followed by docetaxel
      (36 mg/m(2)) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients
      maintained a reduced calcium diet and increased oral hydration. Prostate-specific
      antigen (PSA) response was the primary end point, which was defined as a 50%
      reduction in PSA level confirmed 4 weeks later. RESULTS: Thirty of 37 patients
      (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty
      two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA.
      Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a
      confirmed partial response. Median time to progression was 11.4 months (95% CI,
      8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to
      incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment
      related toxicity was generally similar to that expected with single-agent
      docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected
      by the presence of its companion drug in an exploratory substudy. CONCLUSION: The
      combination of weekly oral high-dose calcitriol and weekly docetaxel is a well
      tolerated regimen for AIPC. PSA and measurable disease response rates as well as
      time to progression and survival are promising when compared with contemporary
      phase II studies of single-agent docetaxel in AIPC. Further study of this regimen
      is warranted.

PMID- 12506181
TI  - Effect of fish oil on appetite and other symptoms in patients with advanced
      cancer and anorexia/cachexia: a double-blind, placebo-controlled study.
AB  - PURPOSE: To determine whether high doses of fish oil, administered over 2 weeks,
      improve symptoms in patients with advanced cancer and decreased weight and
      appetite. PATIENTS AND METHODS: Sixty patients were randomly assigned to fish oil
      capsules or placebo. Appetite, tiredness, nausea, well-being, caloric intake,
      nutritional status, and function were prospectively assessed at days 1 and 14.
      RESULTS: The baseline weight loss was 16 +/- 11 and 16 +/- 8 kg in the fish oil
      (n = 30) and placebo (n = 30) group respectively, whereas the baseline appetite
      (0 mm = best and 10 mm = worst) was 58 +/- 24 mm and 67 +/- 19 mm, respectively
      (P = not significant). The mean daily dose was 10 +/- 4 (fish oil group) and 9 +/
      3 (placebo group) capsules, which provided 1.8 g of eicosapentaenoic acid and
      1.2 g of docosahexaenoic acid in the fish oil group. No significant differences
      in symptomatic or nutritional parameters were found (P <.05), and there was no
      correlation between changes in different variables between days 1 and 14 and the
      fish oil doses. Finally, the majority of the patients were not able to swallow
      more than 10 fish oil capsules per day, mainly because of burping and aftertaste.
      CONCLUSION: Fish oil did not significantly influence appetite, tiredness, nausea,
      well-being, caloric intake, nutritional status, or function after 2 weeks
      compared with placebo in patients with advanced cancer and loss of both weight
      and appetite.

PMID- 12506182
TI  - Dendritic cell-based vaccination in solid cancer.
AB  - PURPOSE: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable
      tool in cancer treatment. This approach has been used mostly in patients in the
      presence of defined tumor antigens such as melanoma. In this study, cancer
      patients with advanced disease that lacks defined tumor antigens were vaccinated
      with tumor lysate-pulsed DCs. PATIENTS AND METHODS: Twenty patients (pancreatic,
      hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV
      disease were enrolled in the study. In 3-week intervals, freshly isolated
      autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte
      macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs.
      These cells were pulsed with autologous tumor lysate and matured with tumor
      necrosis factor alpha. Mature DCs were applied into a groin lymph node, under
      ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given
      subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker
      profile, immune response, and clinical response were determined. RESULTS:
      Vaccination was well tolerated. No physical signs of autoimmunity were detected.
      DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients.
      Tumor marker responses were observed in eight patients. In addition, in three
      patients the generation of interferon gamma-positive T cells was induced during
      the vaccination. Objective changes in measurable lesions or tumor markers were
      evident in seven of 20 assessed patients. None of the patients was found to meet
      the criteria for partial or complete responses. CONCLUSION: These data indicate
      that vaccination with autologous tumor-pulsed DCs generated from peripheral blood
      is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses
      are achievable, even in patients with advanced disease.

PMID- 12506183
TI  - Phase I clinical trial of intrathecal topotecan in patients with neoplastic
      meningitis.
AB  - PURPOSE: A phase I trial of intrathecal (IT) topotecan was performed to determine
      the optimal dose, the dose-limiting toxic effects, and the incidence and severity
      of other toxic effects in patients 3 years and older with neoplastic meningitis.
      PATIENTS AND METHODS: Twenty-three assessable patients received IT topotecan
      administered by means of either lumbar puncture or an indwelling ventricular
      access device (Ommaya reservoir). Intrapatient dose escalation from 0.025 mg to
      0.2 mg was performed in the first cohort of patients. Subsequent cohorts of
      patients were treated at fixed dose levels of 0.2 mg, 0.4 mg, or 0.7 mg. Serial
      samples of CSF for pharmacokinetic studies were obtained in a subset of patients
      with Ommaya reservoirs. RESULTS: Arachnoiditis, characterized by fever, nausea,
      vomiting, headache, and back pain, was the dose-limiting toxic effect in two of
      four patients enrolled at the 0.7 mg dose level. The maximum-tolerated dose (MTD)
      was 0.4 mg. Six of the 23 assessable patients had evidence of benefit manifested
      as prolonged disease stabilization or response. CONCLUSION: The MTD and
      recommended phase II dose of IT topotecan in patients who are 3 years or older is
      0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis
      is in progress.

PMID- 12506184
TI  - A phase I and pharmacokinetic study of pegylated camptothecin as a 1-hour
      infusion every 3 weeks in patients with advanced solid malignancies.
AB  - PURPOSE: To assess the feasibility of administering camptothecin (CPT), the
      prototypic topoisomerase I inhibitor, as polyethylene glycol (PEG)-CPT, a
      macromolecule consisting of CPT conjugated to chemically modified PEG. The study
      also sought to determine the maximum-tolerated dose (MTD) of PEG-CPT,
      characterize its pharmacokinetic behavior, and seek preliminary evidence of
      anticancer activity. PATIENTS AND METHODS: Patients with advanced solid
      malignancies were treated with escalating doses of PEG-CPT as a 1-hour
      intravenous (IV) infusion every 3 weeks. A modified continual reassessment method
      was used for dose-level assignment to determine the MTD, which was defined as the
      highest dose level at which the incidence of dose-limiting toxicity did not
      exceed 20%. RESULTS: Thirty-seven patients were treated with 144 courses of PEG
      CPT at seven dose levels ranging from 600 to 8,750 mg/m(2). Severe
      myelosuppression was consistently experienced by heavily pretreated (HP) and
      minimally pretreated (MP) patients at the highest dose level evaluated, 8,750
      mg/m(2), whereas both HP and MP patients tolerated repetitive treatment at 7,000
      mg/m(2). Cystitis, nausea, vomiting, and diarrhea were also observed but were
      rarely severe. A partial response was noted in a patient with platinum- and
      etoposide-resistant small-cell lung carcinoma, and minor responses were noted in
      one patient each with adenocarcinoma of unknown primary type and osteosarcoma.
      The pharmacokinetics of free CPT were dose proportional. Free CPT accumulated
      slowly in plasma, with maximal plasma concentrations achieved at 23 +/- 12.3
      hours; the harmonic mean half-life (t(1/2)) of free CPT was long (t(1/2), 77.46
      +/- 36.77 hours). CONCLUSION: Clinically relevant doses of CPT can be delivered
      by administering PEG-CPT. The recommended dose for phase II studies in both MP
      and HP patients is 7,000 mg/m(2) as 1-hour IV every 3 weeks. The characteristics
      of the myelosuppressive effects of PEG-CPT, the paucity of severe nonhematologic
      toxicities with repetitive treatment, the preliminary antitumor activity noted,
      and the slow clearance of CPT enabling simulation of desirable pharmacokinetic
      parameters with a convenient single-dosing regimen warrant further disease
      directed evaluations.

PMID- 12506185
TI  - Chemoprevention of melanoma: an unexplored strategy.
AB  - The incidence and mortality of melanoma has continued to increase steeply-faster
      than most other preventable cancers in the United States. Current sun protection
      strategies have yet to reduce this increased incidence and mortality.
      Chemoprevention, defined as the use of natural or synthetic agents to delay,
      reverse, suppress, or prevent premalignant molecular or histologic lesions from
      progressing to invasive cancer, has become an important area in cancer research.
      Melanoma, with its associated risk factors and its known precursors or
      premalignant lesions, should lend itself well to chemoprevention. Prerequisites
      for this research should include determination of the molecular mechanisms of
      ultraviolet (UV) melanomagenesis; use of animal models to test candidate
      prevention agents; use of molecular and histologic markers as surrogate end point
      markers; collection of epidemiological, basic science, or in vitro data on
      potential chemoprevention candidate drugs; and selection of a high-risk patient
      population in which to carry out clinical chemoprevention trials. Preliminary
      data available in all these areas are reviewed. Possible mechanisms and molecular
      targets for the chemoprevention of UV-induced melanoma are discussed. This recent
      information should stimulate research in the chemoprevention of melanoma.

PMID- 12506186
TI  - Uncommon syndromes and treatment manifestations of malignancy: Case 1. Unusual
      association of lupus and sarcoma.

PMID- 12506187
TI  - Uncommon syndromes and treatment manifestations of malignancy: Case 2. Metastatic
      non-small-cell lung cancer presenting with leukocytosis.

PMID- 12506188
TI  - Uncommon syndromes and treatment manifestations of malignancy: Case 3. Richter's
      syndrome heralded by refractory hypercalcemia.

PMID- 12506189
TI  - Uncommon syndromes and treatment manifestations of malignancy: Case 4.
      Periorbital edema and imatinib mesylate therapy for chronic myelogenous leukemia.

PMID- 12506190
TI  - A couple with cancer: conflicting wishes, joint decisions.

PMID- 12506191
TI  - Prognostic value of timing of pulmonary metastases identification in osteosarcoma
      patients.

PMID- 12506192
TI  - Boosting bioavailability to topotecan: what do we gain?

PMID- 12506193
TI  - Photoisomerization of a rotaxane hydrogen bonding template: light-induced
      acceleration of a large amplitude rotational motion.
AB  - Establishing methods for controlling aspects of large amplitude submolecular
      movements is a prerequisite for the development of artificial devices that
      function through rotary motion at the molecular level. Here we demonstrate that
      the rate of rotation of the interlocked components of fumaramide-derived
      [2]rotaxanes can be accelerated, by >6 orders of magnitude, by isomerizing them
      to the corresponding maleamide [2]rotaxanes by using light.

PMID- 12506194
TI  - Functional connectivity in the resting brain: a network analysis of the default
      mode hypothesis.
AB  - Functional imaging studies have shown that certain brain regions, including
      posterior cingulate cortex (PCC) and ventral anterior cingulate cortex (vACC),
      consistently show greater activity during resting states than during cognitive
      tasks. This finding led to the hypothesis that these regions constitute a network
      supporting a default mode of brain function. In this study, we investigate three
      questions pertaining to this hypothesis: Does such a resting-state network exist
      in the human brain? Is it modulated during simple sensory processing? How is it
      modulated during cognitive processing? To address these questions, we defined PCC
      and vACC regions that showed decreased activity during a cognitive (working
      memory) task, then examined their functional connectivity during rest. PCC was
      strongly coupled with vACC and several other brain regions implicated in the
      default mode network. Next, we examined the functional connectivity of PCC and
      vACC during a visual processing task and show that the resultant connectivity
      maps are virtually identical to those obtained during rest. Last, we defined
      three lateral prefrontal regions showing increased activity during the cognitive
      task and examined their resting-state connectivity. We report significant inverse
      correlations among all three lateral prefrontal regions and PCC, suggesting a
      mechanism for attenuation of default mode network activity during cognitive
      processing. This study constitutes, to our knowledge, the first resting-state
      connectivity analysis of the default mode and provides the most compelling
      evidence to date for the existence of a cohesive default mode network. Our
      findings also provide insight into how this network is modulated by task demands
      and what functions it might subserve.

PMID- 12506195
TI  - Protein-facilitated base flipping in DNA by cytosine-5-methyltransferase.
AB  - DNA methylation, various DNA repair mechanisms, and possibly early events in the
      opening of DNA as required for transcription and replication are initiated by
      flipping of a DNA base out of the DNA double helix. The energetics and structural
      mechanism of base flipping in the presence of the DNA-processing enzyme, cytosine
      5-methyltransferase from HhaI (M.HhaI), were obtained through molecular dynamics
      based upon free-energy calculations. Free-energy profiles for base flipping show
      that, when in the closed conformation, M.HhaI lowers the free-energy barrier to
      flipping by 17 kcalmol and stabilizes the fully flipped state. Flipping is shown
      to occur via the major groove of the DNA. Structural analysis indicates that
      flipping is facilitated by destabilization of the DNA double-helical structure
      and substitution of DNA base-pairing and base-stacking interactions with DNA
      protein interactions. The fully flipped state is stabilized by DNA-protein
      interactions that are enhanced upon binding of coenzyme. This study represents an
      atomic detail description of the mechanism by which a protein facilitates
      specific structural distortion in DNA.

PMID- 12506196
TI  - Absence of p16INK4a and truncation of ARF tumor suppressors in chickens.
AB  - The INK4b-ARF-INK4a locus on human chromosome 9p21 (Human Genome Organization
      designation CDKN2B-CDKN2A), and the corresponding locus on mouse chromosome 4,
      encodes three distinct products: two members of the INK4 cyclin-dependent kinase
      inhibitor family and a completely unrelated protein, ARF, whose carboxyl-terminal
      half is specified by the second exon of INK4a but in an alternative reading
      frame. As INK4 proteins block the phosphorylation of the retinoblastoma gene
      product and ARF protects p53 from degradation, the locus plays a key role in
      tumor suppression and the control of cell proliferation. To gain further insights
      into the relative importance of INK4a and ARF in different settings, we have
      isolated and characterized the equivalent locus in chickens. Surprisingly,
      although we identified orthologues of INK4b and ARF, chickens do not encode an
      equivalent of INK4a. Moreover, the reading frame for chicken ARF does not extend
      into exon 2, because splicing occurs in a different register to that used in
      mammals. The resultant 60-aa product nevertheless shares functional attributes
      with its mammalian counterparts. As well as indicating that the locus has been
      subject to dynamic evolutionary pressures, these unexpected findings suggest that
      in chickens, the tumor-suppressor functions of INK4a have been compensated for by
      other genes.

PMID- 12506197
TI  - Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium
      tuberculosis transcription pattern characteristic of nonreplicating persistence.
AB  - The lung is the primary target of infection with Mycobacterium tuberculosis. It
      is well established that, in mouse lung, expression of adaptive, Th1-mediated
      host immunity inhibits further multiplication of M. tuberculosis. Here, real-time
      RT-PCR was used to define the pattern of expression against time of lung
      infection of key genes involved in Th1-mediated immunity and of selected genes of
      M. tuberculosis. Inhibition of bacterial multiplication was preceded by increased
      mRNA synthesis for IFN-gamma and inducible NO synthase (NOS2) and by NOS2 protein
      synthesis in infected macrophages. Concurrently, the pattern of transcription of
      bacterial genes underwent dramatic changes. mRNA synthesis increased for alpha
      crystallin (acr), rv2626c, and rv2623 and decreased for superoxide dismutase C
      (sodC), sodA, and fibronectin-binding protein B (fbpB). This pattern of M.
      tuberculosis transcription is characteristic of the nonreplicating persistence
      [Wayne, L. G. & Sohaskey, C. D. (2001) Annu. Rev. Microbiol. 55, 139-163]
      associated with adaptation of tubercle bacilli to hypoxia in vitro. Based on this
      similarity, we infer that host immunity induces bacterial growth arrest. In IFN
      gamma gene-deleted mice, bacterial growth was not controlled; NOS2 protein was
      not detected in macrophages; sodC, sodA, and fbpB transcription showed no
      decrease; and acr, rv2626c, and rv2623 transcription increased only at the
      terminal stages of lung pathology. These findings define the transcription
      signature of M. tuberculosis as it transitions from growth to persistence in the
      mouse lung. The bacterial transcription changes measured at onset of Th1-mediated
      immunity are likely induced, directly or indirectly, by nitric oxide generated by
      infected macrophages.

PMID- 12506198
TI  - Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE
      like (NUDEL) and inhibits neurite outgrowth.
AB  - Disrupted-in-Schizophrenia-1 (DISC-1) is a gene whose mutant truncation is
      associated with major psychiatric illness with a predominance of schizophrenic
      symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression
      displays pronounced developmental regulation with the highest levels in late
      embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses,
      DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like
      (NUDEL), is associated with cortical development and is linked to LIS-1, the
      disease gene for a form of lissencephaly, a disorder of cortical development. The
      disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not
      wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is
      thought to reflect defects in cortical development that are determined by
      cytoskeletal protein activities, the cellular disturbances we observe with mutant
      DISC-1 may be relevant to psychopathologic mechanisms.

PMID- 12506199
TI  - Positive and negative regulation of APP amyloidogenesis by sumoylation.
AB  - Amyloid beta peptide (Abeta) generated from amyloid precursor protein (APP) is
      central to Alzheimer's disease (AD). Signaling pathways affecting APP
      amyloidogenesis play critical roles in AD pathogenesis and can be exploited for
      therapeutic intervention. Here, we show that sumoylation, covalent modification
      of cellular proteins by small ubiquitin-like modifier (SUMO) proteins, regulates
      Abeta generation. Increased protein sumoylation resulting from overexpression of
      SUMO-3 dramatically reduces Abeta production. Conversely, reducing endogenous
      protein sumoylation with dominant-negative SUMO-3 mutants significantly increases
      Abeta production. We also show that mutant SUMO-3, K11R, which can only be
      monomerically conjugated to target proteins, has an opposite effect on Abeta
      generation to that by SUMO-3, which can form polymeric chains on target proteins.
      In addition, SUMO-3 immunoreactivity is predominantly detected in neurons in
      brains from AD, Down's syndrome, and nondemented humans. Therefore,
      polysumoylation reduces whereas monosumoylation or undersumoylation enhances
      Abeta generation. These findings provide a regulatory mechanism in APP
      amyloidogenesis and suggest that components in the sumoylation pathway may be
      critical in AD onset or progression.

PMID- 12506200
TI  - Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through
      distinct pathways.
AB  - Amyloid beta-protein (Abeta) is linked to neuronal injury and death in
      Alzheimer's disease (AD). Of particular relevance for elucidating the role of
      Abeta in AD is new evidence that oligomeric forms of Abeta are potent neurotoxins
      that play a major role in neurodegeneration and the strong association of the 42
      residue form of Abeta, Abeta42, with the disease. Detailed knowledge of the
      structure and assembly dynamics of Abeta thus is important for the development of
      properly targeted AD therapeutics. Recently, we have shown that Abeta oligomers
      can be cross-linked efficiently, and their relative abundances quantified, by
      using the technique of photo-induced cross-linking of unmodified proteins
      (PICUP). Here, PICUP, size-exclusion chromatography, dynamic light scattering,
      circular dichroism spectroscopy, and electron microscopy have been combined to
      elucidate fundamental features of the early assembly of Abeta40 and Abeta42.
      Carefully prepared aggregate-free Abeta40 existed as monomers, dimers, trimers,
      and tetramers, in rapid equilibrium. In contrast, Abeta42 preferentially formed
      pentamerhexamer units (paranuclei) that assembled further to form beaded
      superstructures similar to early protofibrils. Addition of Ile-41 to Abeta40 was
      sufficient to induce formation of paranuclei, but the presence of Ala-42 was
      required for their further association. These data demonstrate that Abeta42
      assembly involves formation of several distinct transient structures that
      gradually rearrange into protofibrils. The strong etiologic association of
      Abeta42 with AD may thus be a result of assemblies formed at the earliest stages
      of peptide oligomerization.

PMID- 12506201
TI  - Identification of pathogen-specific and conserved genes expressed in vivo by an
      avian pathogenic Escherichia coli strain.
AB  - Escherichia coli is a diverse bacterial species that comprises commensal
      nonpathogenic strains such as E. coli K-12 and pathogenic strains that cause a
      variety of diseases in different host species. Avian pathogenic E. coli strain
      chi7122 (O78:K80:H9) was used in a chicken infection model to identify bacterial
      genes that are expressed in infected tissues. By using the cDNA selection method
      of selective capture of transcribed sequences and enrichment for the isolation of
      pathogen-specific (non-E. coli K-12) transcripts, pathogen-specific cDNAs were
      identified. Pathogen-specific transcripts corresponded to putative adhesins,
      lipopolysaccharide core synthesis, iron-responsive, plasmid- and phage-encoded
      genes, and genes of unknown function. Specific deletion of the aerobactin
      siderophore system and E. coli iro locus, which were identified by selective
      capture of transcribed sequences, demonstrated that these pathogen-specific
      systems contribute to the virulence of strain chi7122. Consecutive blocking to
      enrich for selection of pathogen-specific genes did not completely eliminate the
      presence of transcripts that corresponded to sequences also present in E. coli K
      12. These E. coli conserved genes are likely to be highly expressed in vivo and
      contribute to growth or virulence. Overall, the approach we have used
      simultaneously provided a means to identify novel pathogen-specific genes
      expressed in vivo and insight regarding the global gene expression and physiology
      of a pathogenic E. coli strain in a natural animal host during the infectious
      process.

PMID- 12506202
TI  - Convergence and divergence in the mechanism of SNARE binding by Sec1/Munc18-like
      proteins.
AB  - Sec1Munc18-like (SM) proteins functionally interact with soluble N-ethylmaleimide
      sensitive factor attachment protein receptors (SNARE) in membrane fusion, but the
      mechanisms of these interactions differ. In vertebrates, SM proteins that mediate
      exocytosis (Munc18-1, 18-2, and 18c) bind to the closed conformation of syntaxins
      1-4, which requires the N-terminal H(abc) domains and SNARE motifs of these
      syntaxins. In contrast, SM proteins that mediate Golgi and endoplasmic reticulum
      fusion (Sly1 and Vps45) bind only to short N-terminal sequences of syntaxins 5,
      16, or 18, independently of their H(abc) domains and SNARE motifs. We now show
      that Munc18-1, Sly1, and Vps45 interact with cognate syntaxins via similar,
      autonomously folded N-terminal domains, but the syntaxin 5-binding surface of the
      Sly1 N-terminal domain is opposite to the syntaxin 1-binding surface of the
      Munc18-1 N-terminal domain. In transfected cells, the N-terminal domain of Sly1
      specifically disrupts the structure of the Golgi complex, supporting the notion
      that the interaction of Sly1 with syntaxin 5 is essential for fusion. These data,
      together with previous results, suggest that a relatively small N-terminal domain
      of SM proteins is dedicated to mechanistically distinct interactions with SNAREs,
      leaving the remaining large parts of SM proteins free to execute their as yet
      unknown function as effector domains.

PMID- 12506203
TI  - NDP kinase 2 interacts with two oxidative stress-activated MAPKs to regulate
      cellular redox state and enhances multiple stress tolerance in transgenic plants.
AB  - NDP kinases (NDPKs) are multifunctional proteins that regulate a variety of
      eukaryotic cellular activities, including cell proliferation, development, and
      differentiation. However, much less is known about the functional significance of
      NDPKs in plants. We show here that NDPK is associated with H(2)O(2)-mediated
      mitogen-activated protein kinase signaling in plants. H(2)O(2) stress strongly
      induces the expression of the NDPK2 gene in Arabidopsis thaliana (AtNDPK2).
      Proteins from transgenic plants overexpressing AtNDPK2 showed high levels of
      autophosphorylation and NDPK activity, and they have lower levels of reactive
      oxygen species (ROS) than wild-type plants. Mutants lacking AtNDPK2 had higher
      levels of ROS than wild type. H(2)O(2) treatment induced the phosphorylation of
      two endogenous proteins whose molecular weights suggested they are AtMPK3 and
      AtMPK6, two H(2)O(2)-activated A. thaliana mitogen-activated protein kinases. In
      the absence of H(2)O(2) treatment, phosphorylation of these proteins was slightly
      elevated in plants overexpressing AtNDPK2 but markedly decreased in the AtNDPK2
      deletion mutant. Yeast two-hybrid and in vitro protein pull-down assays revealed
      that AtNDPK2 specifically interacts with AtMPK3 and AtMPK6. Furthermore, AtNDPK2
      also enhances the myelin basic protein phosphorylation activity of AtMPK3 in
      vitro. Finally, constitutive overexpression of AtNDPK2 in Arabidopsis plants
      conferred an enhanced tolerance to multiple environmental stresses that elicit
      ROS accumulation in situ. Thus, AtNDPK2 appears to play a previously
      uncharacterized regulatory role in H(2)O(2)-mediated MAPK signaling in plants.

PMID- 12506204
TI  - Catalysis of electron transfer during activation of O2 by the flavoprotein
      glucose oxidase.
AB  - Two prototropic forms of glucose oxidase undergo aerobic oxidation reactions that
      convert FADH(-) to FAD and form H(2)O(2) as a product. Limiting rate constants of
      k(cat)K(M)(O(2)) = (5.7 +/- 1.8) x 10(2) M(-1).s(-1) and k(cat)K(M)(O(2)) = (1.5
      +/- 0.3) x 10(6) M(-1).s(-1) are observed at high and low pH, respectively.
      Reactions exhibit oxygen-18 kinetic isotope effects but no solvent kinetic
      isotope effects, consistent with mechanisms of rate-limiting electron transfer
      from flavin to O(2). Site-directed mutagenesis studies reveal that the pH
      dependence of the rates is caused by protonation of a highly conserved histidine
      in the active site. Temperature studies (283-323 K) indicate that protonation of
      His-516 results in a reduction of the activation energy barrier by 6.0 kcal.mol(
      1) (0.26 eV). Within the context of Marcus theory, catalysis of electron transfer
      is attributed to a 19-kcal.mol(-1) (0.82 eV) decrease in the reorganization
      energy and a much smaller 2.2-kcal.mol(-1) (0.095 eV) enhancement of the reaction
      driving force. An explanation is advanced that is based on changes in outer
      sphere reorganization as a function of pH. The active site is optimized at low
      pH, but not at high pH or in the H516A mutant where rates resemble the
      uncatalyzed reaction in solution.

PMID- 12506205
TI  - Automatic classification of protein structure by using Gauss integrals.
AB  - We introduce a method of looking at, analyzing, and comparing protein structures.
      The topology of a protein is captured by 30 numbers inspired by Vassiliev knot
      invariants. To illustrate the simplicity and power of this topological approach,
      we construct a measure (scaled Gauss metric, SGM) of similarity of protein
      shapes. Under this metric, protein chains naturally separate into fold clusters.
      We use SGM to construct an automatic classification procedure for the CATH2.4
      database. The method is very fast because it requires neither alignment of the
      chains nor any chain-chain comparison. It also has only one adjustable parameter.
      We assign 95.51% of the chains into the proper C (class), A (architecture), T
      (topology), and H (homologous superfamily) fold, find all new folds, and detect
      no false geometric positives. Using the SGM, we display a "map" of the space of
      folds projected onto two dimensions, show the relative locations of the major
      structural classes, and "zoom into" the space of proteins to show architecture,
      topology, and fold clusters. The existence of a simple measure of a protein fold
      computed from the chain path will have a major impact on automatic fold
      classification.

PMID- 12506208
TI  - Hexaaquanickel(II) bis(hypophosphite).
AB  - The structure of hexaaquanickel(II) bis(hypophosphite),
      [Ni(H(2)O)(6)](H(2)PO(2))(2), has been determined. The crystals are prismatic.
      The packing of the Ni and P atoms (not the entire hypophosphite anions) is the
      same as in the structures of [Co(H(2)O)(6)](H(2)PO(2))(2) and
      [Co(0.5)Ni(0.5)(H(2)O)(6)](H(2)PO(2))(2). The Ni(II) cations have a pseudo-face
      centered cubic cell, with cell parameter a approximately= 10.216 A and
      tetrahedral cavities occupied by P atoms. The Ni(II) cation has
      crystallographically imposed twofold symmetry and has an octahedral coordination
      sphere consisting of six water O atoms, two of which also lie on the twofold
      axis. The planes of oppositely coordinated water molecules are in a cross
      conformation. The geometry of the hypophosphite anion is close to point symmetry
      mm2. The hypophosphite anions are hydrogen bonded to the coordinated water
      molecules.

PMID- 12506209
TI  - Lithium niobium disulfide, Li0.63NbS2.
AB  - Lithium niobium disulfide, Li(0.63)NbS(2), has been prepared by a metathesis
      reaction between physically separated solid reactants, i.e. separated reactant
      metathesis (SRM). Single-crystal data were collected at reduced temperature [150
      (2) K], yielding a refined Li content of y = 0.63 (6). The Li content in the
      crystalline samples was also determined analytically by flame photometry. The
      compound crystallizes in hexagonal space group P6(3)/mmc (No. 194), with Li(+)
      ions situated in octahedral sites between NbS(2) layers.

PMID- 12506210
TI  - Uranyl dinitrate trihydrate, UO2(NO3)2(H2O)3.
AB  - The structure of the title compound, which has been synthesized by evaporation at
      294 K, consists of centrosymmetric uranyl hexagonal bipyramids that share
      opposite equatorial edges with two nitrate triangles, resulting in two distinct
      finite clusters of composition [(UO(2))(H(2)O)(2)(NO(3))(2)]. There are two
      unique symmetrically independent U(VI) positions and two unique nitrate groups.

PMID- 12506211
TI  - Tetraaquabis(carbamoyldicyanomethanido-kappaN)manganese(II) dihydrate.
AB  - The crystal structure of [Mn(C(4)H(2)N(3)O)(2)(H(2)O)(4)].2H(2)O, conventionally
      abbreviated [Mn(cdm)(2)(H(2)O)(4)].2H(2)O, where cdm is
      carbamoyldicyanomethanide, is described. The bond lengths and distances are
      comparable to those previously reported for the isomorphous Ni and Co analogs.
      Molecular units are formed by coordination of the nitrile N atoms of two cdm
      anions and four water molecules to the manganese(II) cation. Although these
      mononuclear molecular species are connected via hydrogen bonding, no magnetic
      ordering was observed down to 1.55 K.

PMID- 12506212
TI  - Bis(7-amino-1,3-benzothiazole-kappaN3)dichlorozinc(II).
AB  - The title complex, [ZnCl(2)(C(7)H(6)N(2)S)(2)], contains a Zn centre with a
      distorted tetrahedral coordination sphere, involving two Cl(-) ligands and two
      endocyclic N atoms from the thiazole moiety [Zn-Cl = 2.2284 (7) and 2.2236 (7) A,
      and Zn-N = 2.081 (2) and 2.041 (2) A]. The interplanar angle between the two
      ligands is 79.32 (6) degrees. The amino groups participate in intermolecular N
      H.Cl hydrogen bonds, with N.Cl distances in the range 3.463 (2)-3.519 (2) A.

PMID- 12506213
TI  - Two polymorphs of bis(1,10-phenanthroline-kappa2N,N')copper(I) iodide.
AB  - The title complex, [Cu(C(12)H(8)N(2))(2)]I, (I), has been crystallized in two
      polymorphic forms, both containing four-coordinate copper. Both forms are
      orthorhombic, with form (Ia) crystallizing in the primitive space group Pban and
      form (Ib) in the c-centred space group Ccca. In (Ia), the complex cation and the
      I(-) anion both have 222 crystallographic symmetry, and in (Ib), the complex
      cation has approximate 222 symmetry, with the I(-) counter-ion distributed over
      three special positions.

PMID- 12506214
TI  - Dichloro[1,1'-(5,9-dithia-2,12-diazoniatrideca-1,12-diene-1,13-diyl)dinaphthalen
      2-olato-kappa2O,O']dimethyltin(IV) acetonitrile solvate.
AB  - Reaction of the potentially hexadentate ligand 1,9-bis(2-hydroxy-1
      naphthalenemethylimino)-3,7-dithianonane with dimethyltin chloride gave the title
      1:1 adduct, in which the long ligand wraps around the SnCl(2)Me(2) unit and in
      which the stereochemistry is fully trans. This compound crystallizes from
      acetonitrile as the 1:1 solvate
      [Sn(CH(3))(2)(C(29)H(30)N(2)O(2)S(2))Cl(2)].C(2)H(3)N. During the reaction, the
      hydroxyl protons move to the N atoms. Most of the chemically equivalent bond
      lengths agree to within experimental uncertainty, but the Sn-Cl bond that is
      inside the ligand pocket is substantially longer than the Sn-Cl bond that points
      away from the long ligand [2.668 (1) versus 2.528 (1) A]. The O-Sn-O angle is
      166.0 (1) degrees. Comparison of the Sn-O, C-O and aryl C-C bond lengths with
      those of related compounds shows that the most important resonance forms for the
      Schiff base aryloxide ligand are double zwitterions, but that the uncharged
      resonance forms having carbonyl groups also contribute significantly.

PMID- 12506215
TI  - Ethyl and isopropyl 4-ferrocenyl-benzoate.
AB  - The title compounds, [Fe(C(5)H(5))(C(14)H(13)O(2))] and
      [Fe(C(5)H(5))(C(15)H(15)O(2))], respectively, contain the ferrocenyl
      eta(5)(C(5)H(4)) and phenylene -C(6)H(4)- rings in a nearly coplanar arrangement,
      with interplanar angles of 6.88 (12) and 10.5 (2) degrees, respectively.
      Molecules of the ethyl ester form dimers through eta(5)(C(5)H(5))C-H...O=C
      hydrogen bonds, with graph set R(2)(2)(20), and, together with Csp(3)
      H.pi(C(5)H(5)) interactions, generate a one-dimensional column (irregular
      ladder). Molecules of the isopropyl ester aggregate through eta(5)(C(5)H(5))C
      H.pi(C(6)H(4)) interactions.

PMID- 12506216
TI  - [7,13-Bis(2-aminobenzyl)-1,4,10-trioxa-7,13
      diazacyclopentadecane]diisothiocyanatobarium(II).
AB  - The X-ray crystal structure of the title complex,
      [Ba(NCS)(2)(C(24)H(36)N(4)O(3))], indicates that the Ba(II) cation is nine
      coordinate in the solid state, being fully encapsulated by the organic receptor
      ligand. The receptor adopts a syn arrangement, with both pendant arms oriented on
      the same side of the crown moiety. The distance between the two amine N atoms is
      3.911 (12) A, while the pivotal N atoms are 5.322 (10) A apart.

PMID- 12506217
TI  - Dichlorobis(DL-proline-kappaO)zinc(II).
AB  - The title compound, [ZnCl(2)(C(5)H(9)NO(2))(2)], crystallizes in the
      centrosymmetric space group C2/c with the Zn atom on a twofold axis. The two
      proline residues in any one complex thus have the same absolute configuration.
      Hydrogen bonding links the molecules into linear chains, which run in the
      crystallographic b direction. The proline residues within any one chain also have
      an identical absolute configuration.

PMID- 12506218
TI  - Bis[mu-6-amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dionato-kappa3O4,N5:O5]-di
      micro-aqua-bis[diaqua[6-amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dionato
      kappa2N1,O2]strontium(II)]: centrosymmetric dimers containing nine-coordinate Sr,
      linked by multiple hydrogen bonds into a three-dimensional framework.
AB  - The title complex, [Sr(2)(C(5)H(5)N(4)O(3))(4)(H(2)O)(6)], forms centrosymmetric
      dimers in which one water ligand bridges two Sr centres and in which one of the
      anionic ligands is bidentate and bonded to just one Sr atom, and the other is
      tridentate and bridges the two Sr centres within the dimer. The dimeric units are
      linked by an extensive series of O-H...O, O-H...N and N-H...O hydrogen bonds to
      form a complex three-dimensional framework.

PMID- 12506219
TI  - Dichloro(4,4'-dinonyl-2,2'-bipyridine-kappa2N,N')platinum(II).
AB  - The title compound, [PtCl(2)(C(28)H(44)N(2))], is a new square-planar Pt(II)
      complex containing a bipyridine moiety with two long alkyl-chain substituents.
      The complex forms a segregated packing structure made up of the alkyl-chain
      layers and paired coordination sites.

PMID- 12506220
TI  - N-ethylpyridinium bis(2-thioxo-1,3-dithiole-4,5-dithiolato)nickelate.
AB  - The title compound, (C(7)H(10)N)[Ni(C(3)S(5))(2)] or (Etpy)[Ni(dmit)(2)] (where
      Etpy is the N-ethylpyridinium cation, C(7)H(10)N(+), and dmit is the 2-thioxo-1,3
      dithiole-4,5-dithiolate dianion, C(3)S(5)(2-)), crystallizes in the P-1 space
      group with two molecules in the asymmetric unit. The [Ni(dmit)(2)](-) monoanion
      has a planar D(2h) conformation, with the central Ni atom and the four
      coordinated S atoms forming an NiS(4) square plane. The six-membered ring of the
      Etpy cation also shows good planarity, as expected. There are two main types of
      disorder in the two Etpy cations. Several short intermolecular interactions are
      present, such as S...S, Ni...S and Ni...Ni, which help to form the enhanced three
      dimensional structure of the crystal.

PMID- 12506221
TI  - A new polymeric phase of zinc(II) oxydiacetate.
AB  - A new polymeric phase of zinc(II) oxydiacetate, catena-poly[[[diaquazinc(II)]-mu
      oxydiacetato] hydrate], [[Zn(C(4)H(4)O(5))(H(2)O)(2)].H(2)O](n), isomorphous with
      the Co homologue [Hatfield, Helms, Rohrs, Singh, Wasson & Weller (1987). Proc.
      Indian Acad. Sci. Chem. Sci. 98, 23-31], is reported. It presents a chain-like
      structure, generated by ZnO(6) cores which are bridged by carboxylate groups in
      an anti-anti conformation along the unique crystallographic b axis. The chains
      are held together through hydrogen-bonding interactions with the three water
      molecules.

PMID- 12506222
TI  - A triclinic polymorph of benzanilide: disordered molecules form hydrogen-bonded
      chains.
AB  - In the P-1 polymorph of benzanilide or N-phenylbenzamide, C(13)H(11)NO, the
      molecules are linked into simple C(4) chains by N-H...O hydrogen bonds. The
      molecules exhibit orientational disorder, but the donor and acceptor in a given
      hydrogen bond may occur, independently, in either the major or the minor
      orientation, such that all four possible N-H.O combinations have very similar
      geometries. The structure of this P-1 polymorph can be related to that of a
      previously reported C2/c polymorph.

PMID- 12506223
TI  - Two polymorphs, with Z' = 1 and 2, of 2-amino-4-chloro-6-morpholinopyrimidine in
      P21/c, and 2-amino-4-chloro-6-piperidinopyrimidine, which is isomorphous and
      almost isostructural with the Z' = 2 polymorph.
AB  - Crystallization of 2-amino-4-chloro-6-morpholinopyrimidine, C(8)H(11)ClN(4)O,
      (I), yields two polymorphs, both with space group P2(1)/c, having Z' = 1 (from
      diethyl ether solution) and Z' = 2 (from dichloromethane solution), denoted (Ia)
      and (Ib), respectively. In polymorph (Ia), the molecules are linked by an N-H...O
      and an N-H...N hydrogen bond into sheets built from alternating R(2)(2)(8) and
      R(6)(6)(40) rings. In polymorph (Ib), one molecule acts as a triple acceptor of
      hydrogen bonds and the other acts as a single acceptor; one N-H...O and three N
      H...N hydrogen bonds link the molecules in a complex chain containing two types
      of R(2)(2)(8) and one type of R(4)(4)(18) ring. 2-Amino-4-chloro-6
      piperidinopyrimidine, C(9)H(13)ClN(4), (II), which is isomorphous with polymorph
      (Ib), also has Z' = 2 in P2(1)/c, and the molecules are linked by three N-H...N
      hydrogen bonds into a centrosymmetric four-molecule aggregate containing three
      R(2)(2)(8) rings.

PMID- 12506224
TI  - Hydrogen bonding in 2-amino-4-methoxy-6-methylpyrimidine, 2-benzylamino-4
      benzyloxy-6-methylpyrimidine and 4-benzylamino-2,6-bis(benzyloxy)pyrimidine: pi
      stacked chains of fused R22(8) rings, and centrosymmetric R22(8) dimers.
AB  - Molecules of 2-amino-4-methoxy-6-methylpyrimidine, C(6)H(9)N(3)O, (I), lie on
      mirror planes in space group Pnma and are linked by two N-H...N hydrogen bonds
      [H...N = 2.26 and 2.34 A, N...N = 3.136 (2) and 3.212 (2) A, and N-H...N = 175
      and 172 degrees ] into chains of edge-fused R(2)(2)(8) rings, which themselves
      are linked into sheets by aromatic pi-pi-stacking interactions. In 2-benzylamino
      4-benzyloxy-6-methylpyrimidine, C(19)H(19)N(3)O, (II), and 4-benzylamino-2,6
      bis(benzyloxy)pyrimidine, C(25)H(23)N(3)O(2), (III), the molecules are linked by
      paired N-H.N hydrogen bonds [H...N = 2.16 A, N.N = 3.039 (2) A and N-H...N = 165
      degrees in (II); H...N = 2.15 A, N...N = 2.980 (2) A and N-H...N = 176 degrees in
      (III)] into centrosymmetric R(2)(2)(8) dimers, with no direction-specific
      interactions between these dimeric units.

PMID- 12506225
TI  - Hydrogen bonding in nitroaniline analogues: hydrogen-bonded sheets in 2-amino-4,6
      dimethoxy-5-nitropyrimidine and pi-stacked hydrogen-bonded sheets in 4-amino-2,6
      dimethoxy-5-nitropyrimidine.
AB  - In 2-amino-4,6-dimethoxy-5-nitropyrimidine, C(6)H(8)N(4)O(4), the molecules are
      linked by one N-H...N and one N-H...O hydrogen bond to form sheets built from
      alternating R(2)(2)(8) and R(6)(6)(32) rings. In isomeric 4-amino-2,6-dimethoxy-5
      nitropyrimidine, C(6)H(8)N(4)O(4), which crystallizes with Z' = 2 in P-1, the two
      independent molecules are linked into a dimer by two independent N-H...N hydrogen
      bonds. These dimers are linked into sheets by a combination of two-centre C-H...O
      and three-centre C-H...(O)(2) hydrogen bonds, and the sheets are further linked
      by two independent aromatic pi-pi-stacking interactions to form a three
      dimensional structure.

PMID- 12506226
TI  - Hydrogen bonding in nitroaniline analogues: a hydrogen-bonded chain of rings in 2
      amino-4-butylamino-6-methoxy-5-nitropyrimidine.
AB  - In the title compound, C(9)H(15)N(5)O(3), in which the molecules exhibit
      orientational disorder, the molecules of the major component are linked by paired
      N-H...O hydrogen bonds [H...O = 2.37 and 2.39 A, N...O = 2.974 (3) and 3.011 (3)
      A, and N-H...O = 126 and 128 degrees ] to form a C(8)C(8)[R(2)(2)(6)] chain of
      rings along [010]. The minor component (6.5% of the molecules) forms a similar
      chain running in the opposite direction.

PMID- 12506227
TI  - Zwitterionic 5-(1-piperidiniomethyl)-1H-tetrazolide.
AB  - The title compound, C(7)H(13)N(5), a tetrazole analogue of betaines, exists as a
      zwitterion, with the H atom of the tetrazole ring being transferred to the
      piperidine ring N atom. The tetrazole ring symmetry is close to C(2v), which
      suggests strong charge delocalization in the N-C-N fragment of the ring. There
      are classical hydrogen bonds in the structure which are responsible for the
      formation of two-membered aggregates.

PMID- 12506228
TI  - N-chloroacetyl-beta-alanine.
AB  - The beta-alanine residue of the title compound, C(5)H(8)ClNO(3), has a ggt folded
      conformation, which is mainly stabilized through intermolecular N-H...O=C (amide
      acid) and O-H...O=C (acid-amide) hydrogen bonds. In addition, a cis conformation
      is found for the Cl-CH(2)-C(=O)-NH torsion angle, which is associated with the
      presence of an intramolecular hydrogen bond.

PMID- 12506229
TI  - N6-furfuryladenine (kinetin) hydrochloride.
AB  - In the title compound, N(6)-furfuryladenin-3-ium chloride, C(10)H(10)N(5)O(+).Cl(
      ), the adenine moiety exists as the N3-protonated N7-H tautomer. The orientation
      of the N6 substituent (furfuryl moiety) is distal to the imidazole ring of the
      adenine base. The dihedral angle between the adenine plane and the furfuryl ring
      plane is 76.1 (2) degrees. Three N-H...Cl hydrogen bonds are responsible for the
      formation of a supramolecular chain-like pattern. These supramolecular chains are
      interconnected by C-H...Cl hydrogen bonds to form a hydrogen-bonded sheet and a
      three-dimensional hydrogen-bonded network.

PMID- 12506230
TI  - Ethyl 3-amino-6-phenyl-4-tolylthieno[2,3-b]pyridine-2-carboxylate.
AB  - In the title compound, C(23)H(20)N(2)O(2)S, the central thienopyridine ring
      system is essentially planar, the dihedral angle between the planes of the two
      rings being 0.3 (2) degrees. The terminal ethyl carboxylate group is twisted by
      26.7 (3) degrees away from the central ring system. A short intramolecular
      hydrogen bond involving the amino N atom and the carbonyl O atom [N...O = 2.806
      (4) A] forms a pseudo-six-membered ring. Significant intermolecular C-H...N, C
      H...O and C-H...pi interactions contribute strongly to the stability of the
      structure, along with weak pi-pi-stacking interactions.

PMID- 12506231
TI  - (R)-(6,6'-Dihydroxybiphenyl-2,2'-diyl)bis(diphenylphosphine oxide) methanol
      solvate.
AB  - The title compound, C(36)H(28)O(4)P(2).CH(4)O, was synthesized directly from the
      methoxy analogue. The crystal structure shows that one OH group interacts with an
      O atom of a phosphine oxide group in an adjacent molecule, while the other OH
      group complexes with the methanol solvent molecule via intermolecular hydrogen
      bonds. An O atom of one phosphine oxide group interacts with the hydroxy H atom
      of methanol via a hydrogen bond. There are intra- and intermolecular pi-pi
      interactions between the phenyl rings. All these interactions result in the
      formation of supramolecular chiral parallelogram channels via self-assembly.

PMID- 12506232
TI  - 4,5,9,10-tetrahydro-4-methyl-2-phenyl-9,10-epoxy-3H,10aH-cyclobuta[a]benzo[2,3,4
      de]isoquinoline-3,5-dione.
AB  - In the title compound, C(21)H(15)NO(3), which is one of the photoreaction
      products of N-methyl-1,8-naphthalenedicarboximide with phenylacetylene, the
      cyclobutene and epoxy rings are trans to each other across the cyclohexene ring
      of the tetralin moiety. The dihedral angle between the mean planes of the
      cyclobutene and cyclohexene rings is 112.80 (2) degrees, while the latter makes a
      dihedral angle of 103.70 (9) degrees with the epoxy ring. The crystal structure
      is stabilized by C-H...O intermolecular interactions.

PMID- 12506233
TI  - 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3
      carbonitrile.
AB  - The supramolecular structure of the title compound, C(18)H(17)ClN(2)O(2), is
      determined by the intersection of two chains formed by N-H...O and N-H...N
      hydrogen bonds, forming a two-dimensional sheet.

PMID- 12506234
TI  - 8-(2-bromo-3-methoxy-3-methylbutyl)-7-methoxycoumarin.
AB  - The title compound, C(16)H(19)BrO(4), is a derivative of osthol, isolated from
      the seeds of Imperatoria Osthruthium. The structure was solved in space group P
      1, with two molecules in the asymmetric unit, and was refined to a final R factor
      of 0.064. The two molecules in the asymmetric unit differ in the orientation of
      their brominated substituent group. The benzopyran ring displays aromatic
      character. The packing of the molecules in the lattice is mainly due to C-H...O
      hydrogen bonds.

PMID- 12506235
TI  - Intermolecular stacking in pyrazolo[3,4-d]pyrimidine-based pentamethylene-linked
      flexible molecules.
AB  - The crystal structures of 1-[5-[4,6-bis(methylsulfanyl)-2H-pyrazolo[3,4
      d]pyrimidin-2-yl]pentyl]-6-methylsulfanyl-4-(pyrrolidin-1-yl)-1H-pyrazolo[3,4
      d]pyrimidine, C(22)H(29)N(9)S(3), and 6-methylsulfanyl-1-[5-[6-methylsulfanyl-4
      (pyrrolidin-1-yl)-2H-pyrazolo[3,4-d]pyrimidin-2-yl]pentyl]-4-(pyrrolidin-1-yl)-1H
      pyrazolo[3,4-d]pyrimidine, C(25)H(34)N(10)S(2), which differ in having either a
      pyrrolidine substituent or a methylsulfanyl group, show intermolecular stacking
      due to aromatic pi-pi interactions between the pyrazolo[3,4-d]pyrimidine rings.

PMID- 12506236
TI  - Two derivatives of (N-phenylthioureidoalkyl)phosphonates.
AB  - The structures of diphenyl [3-methyl-1-(3-phenylthioureido)butyl]phosphonate and
      diphenyl [2-methyl-1-(3-phenylthioureido)butyl]phosphonate, both
      C(24)H(27)N(2)O(3)PS, are reported. In both compounds, the thiourea moiety adopts
      a syn-syn conformation (i.e. the S-C-N-C torsion angles are synperiplanar), which
      enables N-H...O hydrogen bonds to be formed between centrosymmetrically related
      molecules. The geometries around the P atoms can be described as distorted
      tetrahedral. Some of the functional groups in each structure are disordered. The
      bulk of the different alkyl substituents between the amide and phosphonate groups
      influences the molecular conformation and crystal packing. Although the
      structures of these compounds and two related derivatives appear to be similar,
      they are not isostructural.

PMID- 12506237
TI  - 2-aminopyridinium benzoate.
AB  - Cyclic eight-membered hydrogen-bonded rings exist in the title compound,
      C(5)H(7)N(2)(+).C(7)H(5)O(2)(-), involving the 2-aminopyridinium and benzoate
      ions. Each benzoate ion has two intramolecular hydrogen bonds. 2-Aminopyridinium
      benzoate ion pairs are linked by N-H...O hydrogen bonds, with an N...O distance
      of 2.8619 (14) A.

PMID- 12506238
TI  - Three 2-aminopurine derivatives.
AB  - The structure of 2-amino-6-chloropurine, C(5)H(4)ClN(5), (I), comprises a flat
      molecule, with all possible strong hydrogen-bond donors and acceptors involved in
      the hydrogen-bonding network. The structures of 2-amino-6-(4
      chlorophenylsulfanyl)purine hemihydrate, C(11)H(8)ClN(5)S.0.5H(2)O, (II), and 2
      amino-6-(4-methylphenylsulfanyl)purine 0.33-hydrate, C(12)H(11)N(5)S.0.33H(2)O,
      (III), have two and three unique molecules, respectively, and one water molecule
      in their asymmetric units. Both (II) and (III) exhibit elaborate hydrogen-bonding
      networks that involve the S (for both) and Cl [for (II)] atoms in addition to the
      expected strong hydrogen-bonding sites. Both structures also have offset-stacking
      formations of the phenyl and purine rings.

PMID- 12506239
TI  - [Relation of apolipoprotein E polymorphism to clinically diagnosed fatty liver
      disease].
AB  - BACKGROUND/AIMS: Apolipoprotein E (Apo E) is important in plasma lipid metabolism
      and is a component of several plasma lipoprotein-lipid particles. Three major Apo
      E isoforms are encoded by three common allelic forms, epsilon2, epsilon3, and
      epsilon4 at the APO E locus. The goal of this study was to examine the
      association between polymorphisms in the apolipoprotein E gene (APOE) and fatty
      liver disease. METHODS: We examined the distribution of APOE alleles from 116
      fatty liver patients and 50 controls in Korea. RESULTS: The frequencies of APOE
      alleles in fatty liver patients were 6.5% in epsilon2, 85.7% in epsilon3 and 7.8%
      in epsilon4. The corresponding frequencies in control subjects were 4.0% in
      epsilon2, 91.0% in epsilon3 and 5.0% in epsilon4. There were no significant
      differences in the distribution of APOE genotypes between fatty liver patients
      and controls. APOE epsilon2 and epsilon4 allele frequencies in fatty liver
      patients were more than those in controls. However, there was no significant
      differences in APOE epsilon2 and epsilon4 allele frequencies. CONCLUSIONS: These
      results suggest that APOE alleles seem not to be directly associated with the
      pathogenesis of fatty liver disease.

PMID- 12506240
TI  - [Chemokine receptor expression of hepatitis B virus-specific CD8+ lymphocyte in
      chronic B viral infection].
AB  - BACKGROUND/AIMS: The protective role of HBV-specific CD8+ cells is dependent on
      their ability to efficiently migrate to the infected liver, where they may exert
      an effector function. The migratory behavior of CD8+ cells is influenced by their
      expression of different chemokine receptors. This study was intended to analyse
      the pattern of chemokine receptor expression of HBV specific CD 8+ cells in
      chronic B viral infection. METHODS: We analysed the CCR5 and CCR3 profile of HBV
      specific CD8+ cells isolated from the blood and liver of patients with different
      patterns of HBV infection. Purified T cells were stained directly ex vivo, or
      after antigen-specific stimulation, using HBV peptide-specific HLA tetramers and
      monoclonal antibodies to CD8, CCR5 and CCR3, with analysis by flow cytometry.
      RESULTS: In patients with chronic hepatitis B characterised by low levels of
      virus (serum HBV DNA <0.5 pg/mL) and minimal liver inflammation, analysis of
      circulating and intrahepatic CD8+ cells demonstrated that liver infiltrating Tc18
      27-specific cells were preferentially CCR5+ (up to 80% of HBV-specific CD8+
      cells), in contrast to cells of the same specificity within the circulating
      compartment (up to 35% of HBV-specific CD8+ cells). Furthermore, CCR3 was
      expressed by about 10% of Tc18-27+ cells infiltrating the liver, but was absent
      from circulating cells. Following HBV-specific stimulation in vitro the CCR5
      expression of circulating Tc18-27-specific cells was up-regulated, to levels
      found in liver infiltrating cells, whereas CCR3 expression was unchanged.
      CONCLUSIONS: The chemokine receptor profile of HBV-specific CD8+ cells is
      influenced by the anatomical site of these cells, and the clinical pattern of
      disease. The ability of circulating HBV-specific CD8+ cells of patients with low
      replicating virus to upregulate CCR5 suggests that these cells may respond to
      increases in virus replication by efficiently migrating into the infected liver.

PMID- 12506241
TI  - [Gene expression profile in response to hepatitis B virus X gene by using an
      adenoviral vector].
AB  - BACKGROUND/AIMS: Hepatitis B virus (HBV) is the etiological factor for
      hepatocellular carcinoma (HCC). Numerous evidence has indicated a link between
      chronic infection with HBV and the development of HCC. Among the four proteins
      encoded by HBV, Hepatitis B virus X gene(HBx), best characterized as a
      transcriptional transactivator, gained attention owing to its presumptive role in
      oncogenesis. Further, HBx has been shown to stimulate signal transduction
      pathways such as Ras-MAPK pathway, NF-kappa B, and Src kinase. The pleiotropic
      events caused by HBx may be the key to understanding the HBV-mediated
      oncogenicity. However, the specific roles of HBx in oncogenesis remain largely
      elusive. To explore the role of HBx in hepatocarcinogenesis, we examined the
      deregulation of host genes induced by HBx expression. METHODS: HBx was
      ectopically expressed in HepG2 cells using a recombinant adenovirus to
      transiently express HBx. Gene expression profiling of HBx was conducted on cDNA
      microarrays that contained 1,028 cDNAs. RESULTS: A number of oncogenes and genes
      that are involved in cell growth, DNA repair, cell cycle regulation, and cell
      motility were deregulated by HBx. CONCLUSIONS: Theses results suggest that HBx
      regulates transcription in a way that contributes to the proliferation of
      hepatocytes, a probable early event of HCC.

PMID- 12506242
TI  - [Relationship between core gene mutations of hepatitis B virus and response to
      alpha interferon therapy in chronic hepatitis B].
AB  - BACKGROUND/AIMS: Treatment of chronic hepatitis B with interferon results in a
      sustained loss of hepatitis B virus DNA and hepatitis B e antigen (HBeAg) and
      remission of liver disease only in a proportion of cases. Recently, mutations of
      hepatitis B virus (HBV) core gene have been reported as being related to the
      failure of interferon treatment in chronic hepatitis B. This study investigated
      whether core gene mutations of HBV are related to non-response to interferon
      therapy and whether the recurrence of HBeAg and HBV DNA in initial responders to
      interferon therapy is associated with the emergence of HBV core gene mutants.
      METHODS: The precore/core gene sequence was determined by polymerase chain
      reaction (PCR) and direct sequencing of PCR product in serum samples obtained
      before interferon treatment from 10 responders and 10 non-responders to
      interferon therapy. In addition, precore/core gene sequence was determined in
      serum samples obtained before interferon treatment and after recurrence from 10
      patients who showed recurrence of HBeAg and HBV DNA after initial response to
      interferon therapy. RESULTS: In samples from 10 responders, there were 7 missense
      mutations and 71 silent mutations. However, there were 43 missense mutations and
      109 silent mutations in samples from 10 non-responders. In samples obtained
      before interferon treatment from the 10 patients who showed recurrence after
      initial response, 8 missense mutations and 74 silents mutations were found. The
      nucleotide sequences from the samples obtained after the recurrence showed 6
      silent nucleotide substitutions compared with the sequences from the samples
      obtained before interferon treatment. CONCLUSIONS: Mutations in the core protein
      of HBV occur more frequently in non-responders than responders to interferon
      therapy of chronic hepatitis B and may be a factor responsible for the failure of
      interferon treatment. The recurrence of HBeAg and HBV-DNA in initial responders
      to interferon therapy is not associated with the emergence of the HBV core gene
      mutants.

PMID- 12506243
TI  - [Clinical outcome in cases of viral breakthrough during lamivudine therapy in
      chronic hepatitis B patients].
AB  - BACKGROUND/AIMS: Long-term lamivudine therapy can induce the emergence of
      lamivudine resistant hepatitis B virus (HBV) mutants. Clinically emergence of the
      mutant is expressed by the reappearance of disappeared HBV DNA in serum.
      Continued lamivudine treatment has been usually recommended in cases of viral
      breakthrough. However, the clinical outcome in patients with viral breakthrough
      is not clear. The aim of this study was to investigate the clinical course of
      chronic hepatitis B patients after viral breakthrough during lamivudine therapy.
      METHODS: A total of 74 patients with chronic hepatitis B who showed viral
      breakthrough after at least 6 months of lamivudine treatment were included in
      this study. They had positive HBeAg and HBV DNA before treatment. The median
      follow-up duration after breakthrough was 13 months. RESULTS: After viral
      breakthrough, only 8 patients (11%) maintained normal ALT levels and 66 patients
      (89%) showed elevation of ALT. 30 patients (41%) showed acute exacerbation of
      hepatitis (ALT increase over five-times upper normal limit). These acute
      exacerbations occurred within three months after breakthrough in 19 patients
      (63%). In the cases of acute exacerbation, 6 patients showed decompensated
      progression such as elevation of serum total bilirubin. One of them died of
      hepatic failure. A predictive factor for acute exacerbation was not found. HBeAg
      seroconversion occurred in 8 patients after viral breakthrough but their clinical
      course was highly variable. CONCLUSIONS: Chronic hepatitis B patients who had
      viral breakthrough during lamivudine therapy should be followed carefully and
      regularly in mind of potential clinical deterioration. New strategies are needed
      to manage the cases of acute exacerbation after viral breakthrough.

PMID- 12506244
TI  - [Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving
      lamivudine therapy].
AB  - BACKGROUND/AIMS: Long-term efficacy and the rate of viral breakthrough in
      patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is
      uncertain. This study was conducted to determine the rate of viral breakthrough
      according to the HBeAg status and the relation of viral breakthrough with YMDD
      mutants. METHODS: Two hundred and five patients with HBeAg-positive and 49
      patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for
      at least 9 months, were included. The mean durations of the lamivudine treatment
      were 176 months and 155 months in HBeAg-positive and negative patients,
      respectively. Analysis of HBV genome for YMDD mutations was performed by
      restriction-fragment-length polymorphism assay and direct sequencing. RESULTS:
      While the cumulative rates of viral breakthrough at 12th and 24th months of the
      lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and
      39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the
      HBeAg-negative group was significantly lower than in the HBeAg-positive group
      (p<0.01). In multivariate analysis, the only significant factor related to viral
      breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all
      patients with viral breakthrough irrespective of HBeAg status. However, in
      patients without viral breakthrough, the rate of YMDD mutants was significantly
      higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs
      5.1%; p<0.01). CONCLUSIONS: Lamivudine is expected to be more persistently
      effective in HBeAg-negative chronic hepatitis B because of a lower viral
      breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the
      emergence of YMDD mutants.

PMID- 12506245
TI  - [Clinical and virologic characteristics of lamivudine resistance in HBV
      associated chronic liver disease].
AB  - BACKGROUND/AIMS: Lamivudine therapy in chronic hepatitis B has been shown to be
      effective in inhibiting HBV replication. However, lamivudine resistance has been
      developed with prolonged use. We studied to determine the prevalence, predictive
      factors, and clinical outcomes of lamivudine resistance. Mutations in YMDD motif
      of HBV polymerase, which have been associated with lamivudine resistance, were
      also assessed. METHODS: 170 patients with HBV-associated chronic liver disease
      who have received lamivudine for at least one year, were studied. The clinical,
      biochemical, and virologic characteristics were analyzed and compared according
      to presence (resistance group) or absence (non-resistance group) of DNA
      breakthrough. Their clinical outcomes were regularly followed. Stored sera before
      treatment and after DNA breakthrough were examined for detection of HBV
      polymerase mutation by direct sequencing and/or RFLP. RESULTS: Cumulative rates
      of lamivudine resistance after one and two years of treatment were 11% and 34%,
      respectively. In the resistance group, as compared to the non-resistance group,
      age, the presence of HBeAg before treatment, and disappearance of HBeAg during
      treatment, were significantly different. The predictive factors associated with
      lamivudine resistance were not found. ALT and HBV-DNA level after lamivudine
      resistance was variable, but jaundice or hepatic failure was absent. Mutation in
      YMDD motif was detected in 73% and other variable mutations were detected before
      treatment and after DNA breakthrough. CONCLUSIONS: Lamivudine resistance
      increases the longer the duration of treatment and clinical outcomes are
      variable. The mutation in YMDD motif was found in about 2/3 of cases. Other
      causes for lamivudine resistance may be considered.

PMID- 12506246
TI  - [Therapeutic efficacy of lamivudine in patients with hepatitis B virus-related
      decompensated cirrhosis in Korea].
AB  - BACKGROUND/AIMS: Although several clinical trials have suggested that lamivudine
      treatment can be very effective in patients with decompensated HBV-associated
      cirrhosis, its role and clinical efficacy are still uncertain because of the
      study designs. The aim of this study is to evaluate the efficacy of lamivudine in
      consecutively enrolled patients with decompensated cirrhosis. METHODS: Twenty
      four patients with decompensated HBV-associated cirrhosis (Child-Pugh score > or
      =8) were enrolled consecutively and treated with lamivudine 100 mg or 150 mg
      daily for 2-51 months (median: 16 months). They were all positive for HBV DNA and
      21 were positive for serum HBeAg. Eight were Child-Pugh class B and 16 were class
      C. Clinical improvement was defined as a decrease of Child-Pugh score of at least
      2 points. RESULTS: At 6(th) month after lamivudine, all the patients cleared
      serum HBV DNA. The cumulative rates for HBeAg loss were 28.6% at 6(th) and 46.6%
      at 12(th) month. The cumulative viral breakthrough rates at 12(th) and 24(th)
      month were 20.0% and 37.5%. Fourteen patients (60.8%) showed clinical
      improvement, while 8 (34.8%) showed no change and 1 got worse, at 6(th) month
      after lamivudine. Most clinical improvement developed within the initial 6
      months. The cumulative mortality rates were 20.8% at 1 year and 37.5% at 2 year.
      CONCLUSIONS: These data suggest that lamivudine can result in clinical
      improvement in about 60% of patients with HBV-related decompensated cirrhosis.
      Because most improvement occurs within 6 months after starting lamivudine, liver
      transplantation should be actively considered in cases which do not show clinical
      improvement despite 6-month lamivudine treatment.

PMID- 12506247
TI  - [Efficacy and safety of long-term lamivudine therapy in the patients with
      decompensated liver cirrhosis secondary to hepatitis B].
AB  - BACKGROUND/AIMS: Lamivudine use in patients with decompensated cirrhosis B has
      been reported to improve the hepatic function and often delay the need for liver
      transplantation. In the present study, we evaluated the efficacy and safety of
      long-term lamivudine therapy in patients with decompensated cirrhosis by
      comparative study using a matched, untreated cohort. METHODS: 41 patients with
      decompensated cirrhosis B were included for this study (31 male and 10 female;
      mean age, 50 years; mean observation period, 18 months). They were divided into
      two groups: a lamivudine treatment group and an untreated control group. 21
      patients in the treatment group were treated with lamivudine 75 or 150 mg daily
      for at least 12 months. Biochemical and serologic markers were evaluated at two
      to three-month intervals for all patients. Clinical improvement was defined by a
      decrease in the Child-Pugh score of at least 2 points. RESULTS: During the
      observation period, 62% (13/21) was responders, 33% (7/21) was breakthrough, and
      5% (1/21) was non-responder in the treated group. The mean Child-Pugh score was
      significantly improved from 8.6 to 6.0 in the treatment group, but aggravated
      from 8.7 to 10.0 in the control group during the follow-up. The HBeAg
      seroconversion rate was 31% in the treatment group (5/16) and none in the control
      group (0/14). Clinical improvement was observed in fifteen of 21 in the treatment
      group (71%) and only one of 20 in the control group (5%). According to the
      treatment responses, clinical improvement was observed in ten of 13 responders
      (77%), four of 7 breakthrough (57%), and one non-responder. CONCLUSIONS: The long
      term administration of lamivudine for patients with decompensated cirrhosis B is
      effective and safe, although breakthrough and non-response occurred in some
      patients.

PMID- 12506248
TI  - [Suppressive effects of antioxidant DA-9601 on hepatic fibrosis in rats].
AB  - BACKGROUND/AIMS: Oxidative stress is one of the important underlying mechanisms
      of hepatic fibrosis. DA-9601, the ethanol extracts of Artemisia asiatica, has
      been reported to possess strong antioxidative and cytoprotective actions. We
      tried to evaluate whether antioxidant can ameliorate dimethylnitrosamine (DMN)
      induced hepatic fibrosis. METHODS: Rat hepatic fibrosis was induced by
      intraperitoneal administrations of 10 mg DMN six times. Additionally, rats of one
      group were started daily with DA-9601 30 mg/kg containing diets and another group
      was fed a pellet diet containing DA-9601 100 mg/kg. The immunohistochemical
      studies for collagen, alpha-smooth muscle actin (alpha-SMA), and fibronectin, the
      measurements of hepatic malondialdehyde (MDA) and collagens, and the changes of
      liver function profiles were performed. Hepatic stellate cells (HSC) were
      isolated and in vitro effects of DA-9601 on HSC activations were measured.
      RESULTS: DA-9601 significantly attenuated the loss of body weights (p<0.05), the
      reduction of liver wet weights (p<0.05), and the elevation of liver enzymes
      provoked by DMN administrations. DMN injections caused the severe fibrosis of
      portal tract, hepatic inflammation, and significant oxidative damages, but DA
      9601 treatment significantly reduced the mean scores of hepatic fibrosis, the
      amounts of hepatic collagens, and hepatic MDA levels. The prominent decreases in
      the expressions of collagens type I & III, alpha-SMA, and fibronectin or hepatic
      inflammations were observed in DA-9601-treated groups dose-dependently and
      similar efficacy was also proven in in vitro HSC experiment. CONCLUSIONS: DA-9601
      effectively protected rat liver tissues against the DMN-induced hepatic fibrosis.
      Antioxidant could be considered as a supplementary therapeutic for alleviating
      the hepatic fibrosis.

PMID- 12506249
TI  - [Therapeutic efficacy of transjugular intrahepatic portosystemic shunt on
      bleeding gastric varices].
AB  - BACKGROUND/AIMS: Gastric variceal bleeding is a severe complication of liver
      cirrhosis with a high mortality. The purpose of this study was to determine the
      efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in patients with
      gastric variceal bleedings and predictive factors for survival. METHODS: We
      retrospectively analyzed the medical records of 30 consecutive patients with
      gastric variceal bleedings from January 1998 to March 2001. The causes of
      cirrhosis were viral hepatitis in 17, alcohol in 12, and biliary cirrhosis in 1.
      Eighteen patients were in Child-Pugh class B and 9 in class C at the time of
      TIPS. The median follow-up period was 403 days (3-1,215 days). RESULTS: TIPS
      insertion was successful in all 30 patients. The portal pressure gradient (PPG)
      was significantly reduced from 23+/-8 mmHg to 11+/-5 mmHg (p<0.05). Hepatic
      encephalopathy, which developed in 3 patients and was aggravated in 1, was
      improved with medical therapy. Patients with non-alcoholic etiology experienced
      deterioration of liver function after TIPS. Those with alcoholic etiology did
      not. The 6-month and 1-year rebleeding rates were 22% and 41%, respectively. 56%
      of bleeding episodes were associated with stent dysfunction. The degree of PPG
      reduction and the development of stent dysfunction were independent predictive
      factors for rebleeding. The 6-month and 1-year survival rates were 83% and 79%.
      The causes of death were hepatic failure in 3 (37.5%), recurrent variceal
      bleeding in 3, and others in 2. Child-Pugh class C was the only prognostic factor
      for survival. CONCLUSIONS: TIPS was effective in acute hemostasis and the
      prevention of rebleeding in patients with gastric variceal bleeding. Especially,
      it can be safely applied to patients with alcoholic etiology and in Child-Pugh
      class A or B.

PMID- 12506250
TI  - [Comparison of predictive factors related to the mortality and rebleeding caused
      by variceal bleeding: Child-Pugh score, MELD score, and Rockall score].
AB  - BACKGROUND/AIMS: The first episode of variceal bleeding is one of the most
      frequent causes of death in patients with liver cirrhosis. The Child-Pugh(CP)
      scoring system has been widely accepted for prognostic assessment. Recently, MELD
      has been known to be better than the CP scoring system for predicting mortality
      in patients with end-stage liver diseases. The Rockall risk scoring system was
      developed to predict the outcome of upper GI bleeding including variceal
      bleeding. The aim of this study was to investigate the mortality rate of first
      variceal bleeding and the predictability of each scoring system. METHODS: We
      evaluated the 6-week mortality rate, rebleeding rate, and 1-year mortality rate
      of all the 136 patients with acute variceal bleeding without previous episode of
      hemorrhage between January 1, 1998 and December 31, 2000. The CP score, MELD
      score, and Rockall score were estimated and analyzed. RESULTS: Among 136
      patients, 35 patients with hepatoma and 8 patients with follow-up loss were
      excluded. Six-week mortality rate, 1-year mortality rate, and rebleeding rate of
      first variceal bleeding were 24.7%, 35.5%, and 12.9%, respectively. The c
      statistics of CP, MELD, and Rockall score for predicting 6-week mortality rate
      were 0.809 (p<0.001, 95% CI, 0.720-0.898), 0.804 (p<0.001, 95% CI, 0.696-0.911),
      0.787 (p<0.001, 95% CI, 0.683-0.890), respectively. For 1-year mortality rate, c
      statistics were 0.765 (p<0.005, 95% CI, 0.665-0.865), 0.780 (p<0.005, 95% CI,
      0.676-0.883), 0.730 (p<0.01, 95% CI, 0.627-0.834), respectively. CONCLUSION: The
      CP, MELD, and Rockall scores were reliable measures of mortality risk in patients
      with first variceal bleeding. The CP classification is useful in its easy
      applicability.

PMID- 12506251
TI  - [Clinical efficacy of serum PIVKA-II in the diagnosis and follow up after
      treatment of hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist II (PIVKA-II)
      appears to be a useful tumor marker for the evaluation of patients with
      hepatocellular carcinoma (HCC). But the usefulness of PIVKA-II was not yet clear
      in Korea where hepatitis B-virus is endemic. We investigated the usefulness of
      PIVKA-II in the diagnosis and follow-up after treatment of HCC. METHODS: We
      studied patients with HCC which was pathologically confirmed. PIVKA-II was
      measured by enzyme immunoassay. PIVKA- levels before and after treatment, in
      correlation with imaging studies, were analyzed for the comparison of treatment
      responses. Kappa index was obtained. RESULTS: A total of 129 patients were
      included. 93 patients (72%) were HBsAg positive. 86 patients (67%) were PIVKA-II
      >40 mAU/mL. 52 patients (40%) were AFP >20 ng/mL and 77 patients (60%) were AFP <
      or = 20 ng/mL. Of 77 patients, 40 patients (52%) showed PIVKA-II >40 mAU/mL. 68
      of 129 patients were evaluated treatment response. On the basis of radiologic
      response, CR was 33, PR 17, SD 12, and PD 6. Of the 33 radiologic CR patients, 30
      patients were CR and 3 patients were PR by means of PIVKA-II response. Of the 17
      radiologic PR patients, 6 patients were CR and 7 patients were PR. Therefore,
      tumor responses by radiologic and PIVKA-II were well correlated (Kappa index was
      0.59). CONCLUSIONS: PIVKA-II can be used as a useful tumor marker for patients
      with HCC, especially those with low levels of AFP, before and after treatment in
      Korea.

PMID- 12506252
TI  - [Evaluation of various hepatic lesions with positron emission tomography].
AB  - BACKGROUND/AIMS: [18F]FDG-PET is a functional imaging modality reflecting
      cellular glucose metabolism. In most malignant cells, accumulation and trapping
      of [18F]FDG allows the visualization of increased uptake compared with normal
      cells. The aim of this study was to assess the value of PET in differentiating
      benign from malignant hepatic lesions and to determine in which types of hepatic
      tumors PET can help evaluate stage, monitor response to therapy, and detect
      recurrence. METHODS: Eighty patients with liver lesions were enrolled
      (hepatocellular carcinoma 34, cholangiocarcinoma 8, metastatic liver cancer 25,
      hemangioma 6, liver abscess 7). Liver metastases were 22 adenocarcinoma, 2
      lymphoma, 2 squamous cell carcinoma. The PET images of these patients were
      analyzed. SUV and lesion-to-normal liver background SUV ratio were obtained and
      compared among the disease groups. RESULTS: All liver metastases and all
      cholangiocarcinomas had increased uptake value, with SUV ratios greater than 2.
      Hepatocellular carcinoma had SUV ratios greater than 2 in 20 of 34 patients
      (59%). All hemangiomas had poor uptake, a SUV ratio of less than 2. All liver
      abscesses showed definite uptake. CONCLUSIONS: The PET technique using FDG static
      imaging was useful in differentiating malignant from benign lesions of the liver
      in limited situations. Limitations included false negative results in some
      patients with hepatocellular carcinoma. Liver abscesses raised problems in
      differential diagnosis from malignant liver tumors. The findings of this study
      suggest that the PET technique might be applied in tumor staging and the
      detection of recurrence, as well as monitoring responses to therapy for all
      adenocarcinomas and some hepatocellular carcinomas.

PMID- 12506253
TI  - [A case of primary leiomyosarcoma of the liver].
AB  - Primary hepatic leiomyosarcoma is a very rare malignant tumor of the liver and
      rather slowly progressing disease. When the tumor is solitary or even multiple
      but located in one lobe, the treatment of choice is an operation. We report a
      case of huge leiomyosarcoma in a 58-year old female patient treated by surgical
      resection.

PMID- 12506254
TI  - [A case of intraluminal gallbladder hematoma after percutaneous liver biopsy].
AB  - Percutaneous liver biopsy is valued in the diagnosis of diffuse or localized
      liver disease. Serious complications after ultrasonography-guided liver biopsy
      are rare. We report a case of a 69-year-old man who underwent a percutaneous
      liver biopsy for the evaluation of his underlying liver disease with subsequent
      late complication of intraluminal gallbladder hematoma.

PMID- 12506255
TI  - [A case of nodular hepatic involvement of multiple myeloma mimicking
      hypervascular hepatocellular carcinoma].
AB  - Nodular hepatic involvement of multiple myeloma is very rare. We report a case of
      nodular hepatic involvement of multiple myeloma, mimicking hypervascular
      hepatocellular carcinoma.

PMID- 12506256
TI  - [A case of hepatocellular carcinoma with metastasis to gingival mucosa].
AB  - Hepatocellular carcinoma is one of the most common causes of death in Koreans.
      Most cases of hepatocellular carcinoma are beyond the stage of curative resection
      at the time of diagnosis due to extrahepatic metastasis as well as wide
      distribution of tumor in the liver. The lung is the most common site of
      extrahepatic metastasis but metastasis to gingiva is very rare in hepatocellular
      carcinoma. We report a case hepatocellular carcinoma with gingival metastasis in
      a 59 year old male patient.

PMID- 12506257
TI  - [Primary neuroendocrine carcinoma of the liver].

PMID- 12506258
TI  - [Hepatocellular carcinoma with fatty metamorphosis].

PMID- 12506259
TI  - [Ultrastructure of chronic liver diseases; Kupffer cells of the hepatic
      sinusoids].

PMID- 12506260
TI  - [Catatonia: resurgence of a concept. A review of the international literature].
AB  - Catatonia was first described in 1874 by Kahlbaum as being a cyclic disease
      mixing motor features and mood variations. Because most cases ended in dementia,
      Kraepelin recognized catatonia as a form of dementia praecox and Bleuler included
      it within his wide group of schizophrenias. This view influenced the psychiatric
      practice for more than 70 years. But catatonia was recently reconsidered and this
      because of the definition of more precise diagnosis criteria, the discovery of a
      striking association with mood disorders, and the emphasis on effective
      therapeutics. Peralta et al empirically developed a performant diagnostic
      instrument with the 11 most discriminant signs among catatonic features.
      Diagnostic threshold is three or more signs with sensitivity of 100% and
      specificity of 99%. These signs are: immobility/stupor (extreme passivity, marked
      hypokinesia); mutism (includes inaudible whisper); negativism (resistance to
      instructions, contrary comportment to whose asked); oppositionism, other called
      gegenhalten (resistance to passive movement which increases with the force
      exerted); posturing (patient adopts spontaneously odd postures); catalepsy
      (patient retains limb positions passively imposed during examination; waxy
      flexibility); automatic obedience (exaggerated co-operation to instructed
      movements); echo phenomena (movements, mimic and speech of the examiner are
      copied with modification and amplifications); rigidity (increased muscular tone);
      verbigeration (continuous and directionless repetition of single words or
      phrases); withdrawal/refusal to eat or drink (turning away from examiner, no eye
      contact, refusal to take food or drink when offered). Using this diagnostic tool,
      prevalence of catatonic syndrome appears to be close to 8% of psychiatric
      admissions. Other signs are also common but less specific: staring, ambitendance,
      iterations, stereotypes, mannerism, overactivity/excitement, impulsivity,
      combativeness. Some authors complete this description by adding an affective
      dimension which is considered specific. Clinical forms are differentiated
      according to evolution: acute, chronic and periodic forms exist; and
      symptomatology: excited catatonias have a best prognostic than retarded
      catatonias. Malignant catatonia is the most studied form because of its severity
      and high rate of mortality (25%); catatonic patients develop autonomic
      disturbances with labile blood pressure, hyperthermia, diaphoresis, etc.
      Malignant catatonia requires ECT intervention in emergency. While catatonias due
      to general medical conditions are well admitted (first concerned are neurologic
      etiologies) and concern 14,1% of catatonias, psychiatric comorbidity remains a
      problem. The documented decline in the proportion of patients with schizophrenia
      diagnosed as catatonic is congruent with the fact that most studies highlight the
      strong association between catatonia and mood disorders. However, customary
      clinical practice continues to over value diagnostic of schizophrenia because
      catatonic symptoms are recognized as schizophrenic and schizophrenia corresponds
      to a pharmacological target. Other authors stress that on average 20 to 40% of
      catatonias are idiopathic. Conceptual proximity between catatonic symptomatology
      and extrapyramidal syndrome could give some ways for neurobiological grasp of the
      trouble; mesolimbic and mesostriatal dopaminergic imbalance in a frontal lobe
      basal ganglia-brainstem system is supposed to be involved. Treatment procedure
      could be standardized as follows: 1) Withhold neuroleptic medication. Those drugs
      are proven to be lethal when catatonic symptoms are developed; 2) Investigations
      to exclude treatable physical disorders (including standard blood laboratory
      tests, urinary drug screening, electroencephalogram and brain computerized
      tomography); 3) Trial of lorazepam. This therapeutic is safe and 80% effective.
      We propose to administer an initial oral 2,5 mg challenge; catatonic signs are
      rated after the first hours. If necessary, the patient could receive 3 mg/day
      with a 6-day full dose treatment and then, treatment would progressively be
      reduced; 4) If the patient failed to respond to lorazepam, ECT are needed; 5)
      Earlier use of ECT is recommended if autonomic instability or hyperthermia
      appears and malignant catatonia is suspected. In conclusion, catatonia has always
      had an unstable and blurred place in the psychiatric nosography since its first
      description. It has been incorporated within the group of schizophrenias and
      underdiagnosed for a long time, but has been predominantly associated with mood
      disorders for the last ten years. Psychopathological considerations, particularly
      on cognitive and affective status of catatonic patients, should clarify the
      nosologic discussion.

PMID- 12506261
TI  - [Etiology of adult insomnia].
AB  - In the article, the author develops an analysis of external and intrapsychic
      factors related to adults' insomnia. First she undertakes a literature review to
      describe semiological, evolutive and etiological levels of insomnia. From a
      semiological point of view, it is usual to differenciate initial insomnia
      (associated to the first phase of sleeping), intermittent insomnia (related to
      frequent awakenings) and final insomnia (related to early morning awakenings).
      From an evolutive point of view, we can identify transitory insomnia
      (characterized by frequent awakenings) and chronic insomnia. On the other hand,
      we are allowed to distinguish organic insomnia (disorder where an organic
      cerebral injury is demonstrated or suspected) from insomnias related to
      psychiatric or somatic disease or idiopathic one. Then, the author makes a
      literary review to identify various insomnia causes and points out. Social
      factors: insomnia rates are higher by divorced, separated or widowed people.
      Percentages are higher when scholastic level is weak, domestic income is less
      then 915 O a month, or by unemployed people. Besides, sleep quality is
      deteriorated by ageing. Sleeping and waking rhythm is able to loose its
      synchronization. Complaints about insomnia occur far frequently from women than
      men. Environmental factors: working constraints increase sleep disorders. It is
      possible to make the same conclusion when we have to face overcharge of external
      events, deep intrapsychic conflicts (related to grief, unemployment, damage or
      hospitalization) or interpersonal conflicts' situations where we are confronted
      to stress related to socio-affective environment, lack of social support or
      conjugal difficulties. Medical and physiologic causes: legs impatience syndrome,
      recurrent limbs shakings syndrome, breathe stop during sleep, narcolepsy,
      excessive medicine or hypnotic drugs use, some central nervous system injuries,
      every nocturnal awakening (related to aches.), surgical operation.
      Chronobiological factors: night working or day-night shift produce insomnia by
      desynchronization. It is the same for time lag related to jet-lag flights.
      Significant gaps between the internal biological clock and environmental
      synchronizators, such as phase delay sleep, phase advance sleep, sleep-waking
      cycle longer than 24 (25) hours, or variations in sleep-awakening cycle, are of
      less importance. Toxic factors are numerous: amphetamines, antidepressors,
      medication against anorexia and tubercular disease, caffeine and alcohol
      excessive use, chronic alcoholism. Behavioral factors: enduring insomnias are
      related to poor nightroutines (to go to sleep too early, to read or to look at
      T.V. when going to bed). The same effect is produced by regular intellectual
      activities close to bedtime or by a late meal in the evening, by an noisy or
      unhealthy environment, by physical hyperactivity or sleeping after each lunch.
      Psychiatric factors: insomnia often appears with psychiatric disorders such as a
      major depressive episode, an anxiety disorder or schizophrenia. Insomnia also is
      able to open a delirious disorganization or a manic access. Psychological
      factors: overstimulation of waking system (related to stress overdose or
      intellectual hyperactivity), conditioning phenomena, fear of not falling asleep,
      intrapsychic and interpersonal conflicts. Third, the author put hypothesis about
      psychodynamic etiology of chronic insomnia. Following a first assumption,
      insomnia should be a result of anguish excess related to intrapsychic (and not
      interpersonal) conflicts which can't lead to a mental elaboration. These
      conflicts run over dream protective function, generating a breakdown of dream
      symbolization function. At a clinical level, we are in some cases in front of
      people enduring sleeping insomnia but more often, we are confronted with an
      intermittent or early waking insomnia sometimes associated with nightmares.
      Following a second assumption, insomnia should be a result of psychic functioning
      invalidation. Here, failure of dream protective and symbolization function is
      related to anguish excess associated with an amount of external conflicts.
      Overwhelmed by concretude, insomniac patients present an alexythimic intrapsychic
      functioning forbiding dream realization. These persons have no possibility to
      elaborate conflicts especially external overcharge, using dreams or imagination
      to escape from an intrusive reality and regress to sleeping. Here we are in front
      of initial sleep insomnia. Following a third hypothesis, some insomnias are
      related to wakings associated with repetitive nightmares. This type of insomnia
      should be related to a past traumatic event or activated by actual existential
      context and produces a too important anguish charge to follow a mental
      elaboration process and lead to mental symbolic representation. Following a
      fourth hypothesis, some insomnias are in relation with an impossibility to accept
      passive position. The last one will expose to a danger consisting either of
      castration or loneliness and death. To conclude, the author suggests some
      preventive perspective to face insomnia. Especially, she points out limits of
      pharmalogical treatments. She underlines the necessity to promote no medical
      methods to facilitate sleep induction and maintenance, including sleep hygiene
      measures, relaxation, psychotherapic approach and behavioral methods. She
      emphasizes the danger of a reductive approach of insomnia which would be focused
      on a single medical, psychological or environmental dimension. Last but not
      least, she makes methodological propositions to test from a clinical point of
      view the four psychodynamic exposed hypotheses.

PMID- 12506262
TI  - [Clinical and biological specificities of female alcoholism].
AB  - Even though the number of alcohol-dependent women is only about 1/3 of the number
      of alcoholic men, the alcoholism in women, by its clinical features and its
      course, is the source of therapeutic and economic stakes, particularly in young
      women among whom an increase of alcohol consumption related problems is reported.
      Another specificity of the female alcoholism is the lack of care seeking, whereas
      women have tendency globally to solicit more often care structures than men.
      Women represent only 1/4 of the overall treated alcoholic patients. The main
      explanation for this phenomenon is the pejorative social and moral connotation of
      the female alcoholism, with frequent feelings of shame and deep guilt, that also
      account for the frequency of hidden and lonely alcohol intakes. The female
      alcoholism is essentially characterized by an increased vulnerability to the
      toxic effects of the alcohol, whereas the pathological consumption starts later
      and with smaller daily amounts. Most studies have revealed a higher vulnerability
      in women to somatic complications directly attributable to the alcohol organs
      toxicity, such as hepatic cirrhosis and cardiovascular complications (high blood
      pressure, non obstructive cardiomyopathy). The reported brain morphological
      abnormalities could also occur more precociously in alcoholic women than in men.
      A decreased corpus callosum size among alcoholic women, but not in alcoholic men,
      was thus found in a recent study, compared with healthy controls. Among the
      different hypothesis proposed to explain this increased alcohol toxicity, the
      most incriminated is higher alcohol blood rates for the same ingested amount,
      mainly of the fact of a lower size with a weaker proportion of the bodily total
      water, but also of weaker concentrations of gastro-intestinal tract ADH, or of a
      longer metabolism during some menstrual phases. Indeed, some experimental studies
      on animal showed that the alcohol toxic effects may occur only from a threshold
      of alcohol blood rate. More recent studies suggest that the explanation to keep
      is more related to the lower gastric metabolism in women (lower ADH activity),
      than the difference of gastric volume or alcohol hepatic oxidation. Regarding to
      comorbidity, in the Epidemiologic Catchment Area survey, 65% of women, versus 44%
      of men, with abuse and/or dependence to alcohol had at least one another life
      time psychiatric disorder (mainly depression and anxiety disorders), compared to
      36% of the overall women of the studied sample. On the other hand, the alcohol
      dependence is, more often than in men, secondary to other psychiatric disorders,
      essentially depressive episodes, but less associated to antisocial behaviours.
      Among the different etiopathogenic factors involved in the alcohol dependence
      occurrence, genetic factors seem to have a determinant impact. According to the
      previous family, separation/adoption and twins studies performed, genetic factors
      could explain 50 to 60% of the alcoholism vulnerability in both men and women. In
      this context, and whereas we assist to the development of etiopathogenic models
      with new therapeutic perspectives in alcohol dependence, it seems necessary not
      to neglect female alcoholism specificities.

PMID- 12506263
TI  - [Anxiety disorders in private practice psychiatric out-patients: prevalence,
      comorbidity and burden (DELTA study)].
AB  - Few data are currently available on the prevalence and associated characteristics
      of anxiety disorders in psychiatric out-patients in France, in particular in the
      private health-care. However, this represents one of the principal systems of
      care for patients suffering from anxiety disorders, with a possible direct access
      and several types of treatments available (pharmacotherapy but also different
      kinds of psychotherapy). The aim of our study was to describe the prevalence of
      anxiety disorders in a large sample of patients consulting in the private sector,
      and in addition to study the comorbidity, the severity of the disorders, their
      consequences on quality of life and health care consumption. The studied patients
      were included and assessed by 501 psychiatrists from all the country, at the time
      of a first visit. Inclusions were to be made in a consecutive way, but with the
      exclusion of psychotic disorders and dementia. A sample of 1 955 patients was
      obtained, and all subjects had a standardized diagnostic assessment with the Mini
      International Neuropsychiatric Interview (MINI) and with various dimensional
      scales of symptomatology severity, quality of life, and health care consumption.
      On the whole, at least one current anxiety disorder was found in 64.3% of the
      patients, while 55% had a depressive disorder. Individually, the prevalence rates
      are 29.4% for generalized anxiety disorder, 25.9% for agoraphobia, 19.2% for
      panic disorder, 15.3% for social phobia, 11.4% for obsessive-compulsive disorder,
      and 5.4% for post-traumatic stress disorder (PTSD). A history of suicide attempts
      was found in 12-20% of patients, and an elevated suicide risk was found for
      example in 25% of PTSD patients. The scores of the symptomatic scales, adaptation
      and quality of life measure show a very significant anxious symptomatology, with
      serious functional consequences. Approximately 75% of patients had another
      medical consultation during the three previous months, and 9% have been
      hospitalized. An interruption of work was found in 25% of the patients during the
      last three months, in average for 35 days. Concerning drug consumption before the
      visit by anxiety disorders patients, the preponderance of anxiolytic use is
      notable (85 to 98% according to categories of anxiety disorders) when compared to
      that of antidepressants (20 to 40%). Moreover, 38.4% of the whole sample took an
      anxiolytic once a day for at least three months and about 40% of them had
      dependence symptoms. In conclusion, this study showed the quantitative importance
      of anxiety disorders among psychiatric out-patients in the private practice
      sector in France, all the categories of anxiety being represented, and the high
      level of severity and burden of these disorders. Compared to some data published
      before, the prevalence rates of these anxiety disorders seem to be increasing.

PMID- 12506264
TI  - [Personality disorders in a nonclinical sample of adolescents].
AB  - OBJECTIVE: To examine the comorbidity of borderline personality disorder and
      other personality disorders in a nonclinical sample of high-school students.
      METHOD: 311 high-school students who completed the French version of the CES-D
      (Center for Epidemiological Studies-Depression Scale), were asked to participate
      to interviews evaluating personality functioning: 60 subjects (19%) accepted to
      participate in the study. The mean CES-D score of these 60 subjects (16 boys, 44
      girls, mean age=17.7 1.7) was significantly higher than the mean score of the
      whole sample (23.9 10.4 versus 16.7 9.8). Thus the interviewed sample was not
      representative of the population of high-school students. Subjects were assessed
      using the major depressive episode module of the MINI (Mini International
      Neuropsychiatric Interview) and the SIDP IV (Structured Interview for DSM IV
      Personality). Inter-rater reliability was determined by comparing the independent
      ratings of interviewers and an experienced clinician on a random sample of 20
      interviews. For DSM IV borderline personality disorder diagnosis, the Cohen's
      kappa coefficient was 0.85. For personality disorder criteria, kappa ranged from
      0.6 to 1.0 (average kappa=0.79). RESULTS: Sixteen of these subjects (26,7%, 4
      males, 12 females) received a diagnosis of borderline personality disorder
      according to DSM IV criteria. The mean CES-D score of borderline subjects (30.6
      10.2) was significantly higher than the mean score of nonborderline subjects
      (21.6 10.5). Of the 16 borderline subjects, 11 (75%) received a diagnosis of
      major depressive disorder versus 14 (31%) of the non borderline subjects. None of
      the other personality disorders approached the frequency of borderline
      personality disorder. The next most frequent diagnoses were depressive and
      dependent personality disorders which occurred in respectively in 16.6% and 10%
      of the 60 subjects. All the personality-disorders occurred at higher rates in the
      group with borderline personality disorder with the exception of obsessive
      compulsive personality disorder which was diagnosed only in nonborderline
      subjects. Of the 16 borderline subjects, 11 (68.7%) met the criteria for another
      personality disorder which were depressive personality disorder (N=5), paranoid
      personality disorder (N=4), dependent personality disorder (N=3), antisocial
      personality disorder (N=2), histrionic personality disorder (N=2), avoidant
      personality disorder (N=2), negativistic personality disorder (N=2), schizotypal
      personality disorder (N=1), narcissistic personality disorder (N=1), self
      defeating personality disorder (N=1). The optional diagnoses (self-defeating,
      depressive and negati-vistic personality disorders) accounted for 8 of 23 (34.7%)
      cases of personality disorders diagnosed among borderline subjects. Among these
      11 adolescents, 5 received 2 diagnoses of personality disorders (borderline and
      paranoid personality disorders, N=1; borderline and dependent personality
      disorders, N=1; borderline and depressive personality disorders, N=3), 3 received
      3 diagnoses (borderline, antisocial and histrionic personality disorders, N=1;
      borderline, avoidant and negativistic personality disorders, N=1; borderline,
      depressive and negativistic personality disorders, N=1), 3 received 5 diagnoses
      (borderline, paranoid, histrionic, narcissistic and dependent personality
      disorders, N=1; borderline, paranoid, dependent, avoidant and depressive
      personality disorders, N=1; borderline, paranoid, schizotypal, antisocial and
      self-defeating personality disorders, N=1). Among the 44 adolescents (12 boys, 32
      girls) without borderline personality disorder, 10 (22.7%) (3 boys, 7 girls) met
      the criteria for another personality disorder which were depressive personality
      disorder (N=5) or cluster C disorders -obsessive-compulsive personality disorder
      (N=4), dependent personality disorder (N=2), avoidant personality disorder (N=1) 
      with the exception of one diagnosis of histrionic personality disorder. Two
      subjects received 2 diagnoses (obsessive-compulsive and depressive personality
      disorder). The internal consistency of personality disorders criteria was
      assessed with Cronbach's alpha coefficient. Borderline personality disorder
      criteria had high internal consistency (0.82). The factor structure of borderline
      personality disorder criteria was studied with an exploratory factorial analysis
      which extracted three factors. The eigenvalues were 3.70, 1.06, and 1.01.
      Confirmatory factorial analyses were conducted. The correlated two-factor model
      and the three-factor model fit the data well but the correlation between factors
      was, however, judged too high, ranging from 0.70 to 0.78. The one-factor model
      proved to have a good fit (Goodness of Fit Index=0.89, Comparative Fit
      Index=0.90, Root Mean Square Residual=0.07). As a previous study showed the
      frequency of two schizotypal personality disorder criteria (odd beliefs/magical
      thinking experiences and unusual perceptual experiences), an exploratory
      factorial analysis was performed on the combined set of criteria of borderline
      and schizotypal personality disorders. It yielded 2 factors: the first factor
      consisted of all the borderline personality disorder criteria, odd
      beliefs/magical thinking, and unusual perceptual experiences and could be called
      the borderline factor; the second factor consisted of the paranoid and the social
      avoidance criteria and could be called the interpersonal hypersensitivity factor.
      A confirmatory factor analysis showed that this two-factor model provided a good
      fit to the data (GFI=0.82, CFI=0,91, RMSR=0.10). The correlation between factors
      was weak (0.25). These results suggest that odd beliefs/magical thinking and
      unusual perceptual experiences are a component of borderline symptomatology in
      adolescents. DISCUSSION: The high frequency of major depressive disorder and
      personality disorders in the interviewed sample may be due to the possibility
      that adolescents with psychological problems have used the interview as a way to
      obtain attention and support from a psychologist. The interviewed sample, which
      was characterized by a high intensity of depressive symptomatology and by a high
      frequency of borderline personality disorder, could thus be seen as intermediate
      between a clinical and a community sample. Our results may be more generalizable
      to an outpatients population of adolescents. This study found conflicting results
      about the construct validity of borderline personality disorder in adolescent.
      The high internal consistency and the one-factor structure of the borderline
      personality disorder criteria argue for their validity in adolescents. However,
      the high rates of comorbidity of borderline personality disorder with depression
      and other personality disorders, extended to clusters A, B and C and to optional
      diagnoses, suggest the lack of construct validity of either borderline
      personality or cluster B disorders in adolescents. CONCLUSION: Borderline
      symptomatology in adolescents appears more in adequacy with a dimensional model
      than with a typological classification. More studies are needed to assess and
      improve the construct validity of borderline personality disorder in adolescents.

PMID- 12506265
TI  - [Assessment of premenstrual dysphoric disorder symptoms: population of women in
      Casablanca].
AB  - Menstruation is a biological phenomenon that has been subject of myths and taboos
      within and among various cultures. These myths distort the reality surrounding
      menstruation and create ambivalent feelings about the value and usefulness of
      this function outside of its necessity as mean of reproduction. Thus studies
      concerning menstruation need to take into account cultural and psychosocial
      factors that define the meaning, values and behavior associated with this
      biological phenomenon. According to several studies, 70% of women experience
      psychological faintness during this menstrual phase, 40% of them have these
      symptoms at each menstruation and between 3 to 8% of them suffer severely
      reacquiring medical support. This entity called premenstrual dysphoric disorder
      is defined by the presence of several symptoms (distress, tension, irritability,
      moodiness.) with a significant impairment in work or social functioning beginning
      during the week before and ending within a few days after the onset of menses.
      Several studies conducted over the past few years suggested that selective
      serotonin reuptake inhibitors (SSRIs) and serotoninergic tricyclic drugs may be
      more effective than other types of antidepressants in treating PMS symptoms. Two
      protocols are proposed; a continuous treatment or intermittent use during few
      days during pre-menstrual and menstrual phase for several cycles. The objective
      of the current study was to evaluate the prevalence of a potential premenstrual
      dysphoric disorder (PMDD) during one menstrual cycle, in a representative sample
      of general population of Casablanca, according the DSM IV criteria. On the other
      hand, a questionnaire, available from the authors, was used to explore socio
      demographic data. Among 618 women interviewed, 310 met the criteria of a
      potential PMDD (50.2%). The mean age of the population with PMDD was 32.2 8 years
      ranging from 20 to 50 years; 54.8% of them were married, 33.9% of them were
      single and 66.5% of them had between 1 to 4 children. Two third of them were
      without a professional activity. During this premenstrual phase the following
      symptoms were found among the whole sample: marked depressive mood, feeling of
      hopelessness, or self-depreciation thoughts (77.7%, n=241%); difficulty of
      concentration (65%, n=201); marked change in appetite, overeating or specific
      food craving (82.8%, n=256); marked affective lability, with sadness tearful and
      increased sensitivity to rejection (65.8%, n=204); hypersomnia or insomnia
      (59.7%, n=185); subjective sense of being overwhelmed or out of control (55.7%,
      n=172); lethargy, excessive fatigability (91.6%, n=283); physical symptoms
      including breast tenderness, swelling, headache, joint or muscular pain, and a
      sensation of bloating and weight gain (81.9%, n=253). The most severe symptoms
      were fatigue and irritability. On the other hand, 73.9% of the sample had a
      disturbance in their socio-professional lives as a consequence to the
      psychological disturbances. Half of these women consulted a physician, mostly a
      general practitioner. These data are in accordance with the literature,
      confirming that this disorder is common and has a bad impact on mental health and
      on quality of life of the women suffering from PMDD.

PMID- 12506266
TI  - [Loss of motivation and frontal dysfunctions in old patients].
AB  - Loss of motivation and frontal dysfunction are frequent in old people. Motivation
      refers to what drives acts and relationships. The loss of motivation has some
      specific characteristics from depression: loss of sens of meaning, loss of
      commitment for others, disinterest for daily activities. The frontal function is
      related to speed of acting, emotional system, anticipating of the future. All
      these points are altered in demotivated patients. For these reasons we assayed to
      analyse the possible links between loss of motivation and frontal dysfunctions.
      METHODS: The focus of this assay was to determine and to precise the functional
      links between frontal brain and loss of motivation in old people; 45 old patients
      cared in a day care hospital were proposed to participate to neuropsychologic
      evaluation. After their agreement and their family acceptation if they were
      demented, they were assessed by a practitioner, then by 2 different
      psychologists. They were evaluated for cognition (MMS), depression (Cornell's
      scale), apathy (Marin's scale), age and scholarships level. In a other time, they
      were tested with different frontal tests: Trail making A and B, Wisconsin, BREF
      (frontal battery of psychological tests) ana-lyse concerned speeds, number and
      natures of errors, habilities for matching categories. Loss of demotivation was
      scored on EAD scale. Statistical analysis was done with Systat 10 and Statview
      software. RESULTS: It could be notice the significant negative links between EAD
      scores and the BREF scales, or with the number of categories found with the
      Wisconsin test. The more motivated the patients are the best results they have
      with their frontal tests. There are positive and significant links between EAD
      score and the number of errors at the Wisconsin test, and especially with
      repetitive errors either with this test or with BREF test. Repetitive errors and
      the number of errors, pointing some frontal dysfunctions are associated with a
      loss of motivation. Considering BREF sub-items, it could be shown the negative
      links between EAD scores and programmation or inhibition sub-items. All these
      points persist in a statistical model including pathology, cognitive levels,
      depression level at the Cornell's scale, age or scholarship level. We do not find
      a link between EAD scores and the time obtained with the Trail making test.
      CONCLUSION: Loss of motivation is associated with some frontal impairment
      responsible for numerous errors in tasks. A good motivation of old people is
      associated with good frontal habilities especially in complex tasks or in
      programming capacities of old patients. There is no links between the speeds of
      tasks and the level of motivation. Motivation could be so related with orbito
      frontal brain activities.

PMID- 12506267
TI  - [Hepatic tolerance of atypical antipsychotic drugs].
AB  - The strategy in the choice of antipsychotic agent must take into account the
      hepatic tolerance according to non-negligible incidence of liver disorders among
      psychiatric population (presence of risk factors like alcoholism, drugs of abuse
      intake, polymedication including potentially hepatotoxic drugs.). More than 1 000
      drugs have been listed as being responsible of hepatic side effects; 16% of these
      agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or
      SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in
      biological or/and clinical hepatotoxicity. For these reasons, some psychotropic
      agents have been withdrawn of the pharmaceutical market like alpidem or
      medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic
      drugs, has been withdrawn recently, as well. Isolated elevations of hepatic
      enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%)
      but also with other classes of neuroleptic agents, as well. On the contrary,
      clinical hepatitis have been more rarely described with neuroleptic drugs like
      phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of
      hepatotoxicity is based on biological parameters (elevation of alkaline
      phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis,
      jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical
      diagnosis and the research of its origin may include many investigations like
      abdominal ultrasonogram and percutaneous liver biopsy. The present article
      describes the cases of hepatic disorders reported with AAD (Atypical
      Antipsychotic Drugs), which are available in France (amisulpride, clozapine,
      olanzapine, risperidone). This new pharmacological class of antipsychotic drugs
      has showed great interest to improve negative symptoms of schizophrenia and to
      reduce disabling side effects like dystonia. According to the bibliographic data
      available, the following points and information must be clinically taken into
      account. Frequency of hepatic troubles: according to the bibliographic data, AAD
      appeared generally well tolerated in most cases. The frequency of hepatic
      troubles remains in general very low or rare. The cases published were observed
      with clozapine, olanzapine and risperidone. Nevertheless, some authors have
      observed higher frequency of hepatic enzymes elevation with some AAD. In an
      investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol
      (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase
      versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical
      observations, asymptomatic biological disorders of the hepatic function are
      generally described but cytolytic or cholestatic hepatitis were reported, as
      well. Symptomatic hepatic dysfunctions were, sometimes, associated with other
      disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check
      up may be relevant in case of significant side-effect outcome. Delay time before
      the hepatic episode: hepatic injuries generally occurred within the first weeks
      of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12
      days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone,
      respectively. These delay times are very similar to those observed with other
      psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the
      responsible agent: all cases were reversible after the AAD withdrawal except with
      one patient (39 years old) treated by clozapine (350 mg/day) who developed a
      fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases,
      the AAD was withdrawn after the hepatic episode according to the significant risk
      of irreversible alteration. Nevertheless, normalization of hepatic enzymes has
      been described despite AAD maintenance at the same dosage or after dosage
      reduction. Rechallenge of clozapine after a first episode was performed for three
      patients, only one redeveloped a new hepatic disorder. According to different
      authors, special care is required if maintenance or rechallenge of the agent is
      indispensable after a first episode of isolated hepatic enzyme elevation (i.e
      resistance or intolerance to other treatments). In this case, biological and
      clinical supervision has to be carefully scheduled, which demands a satisfactory
      compliance from the patient. On the contrary, in case of clinical hepatotoxicity,
      rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic
      troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to
      phenothiazine drugs, no information is available on the respective rule of the
      agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been
      reported, suggesting a possible immuno-allergic mechanism. Presence of risk
      factors: risk factors have been retrieved, in some observations, like high daily
      dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of
      hepatic disorders like Gilbert syndrome. Special care is advisable with these
      patients. As hepatotoxicity has been observed after surdosage (or suicide
      attempt), a hepatic check-up has to be performed in these clinical situations. Co
      medication with hepatotoxic drugs may increase the risk as it has been suggested.
      In many observations, co-medication made difficult the incrimination of the AAD
      in the hepatic disorders outcome. Monotherapy has the great advantage to make
      easier the withdrawal of the responsible agent and its substitution. As drugs of
      abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they
      represent a probable factor of risk. Moreover, their detection is fundamental
      during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is
      mainly based on the chronology between agent introduction and hepatic disorder
      onset but other causes must be excluded. Bibliographic data analysis greatly
      contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article
      emphasized the limits of bibliographic review to compare drugs towards tolerance.
      Most of the bibliographic data were case-reports for which it was sometimes
      difficult to provide absolute evidence of the responsibility of the agent.
      Moreover, spontaneous notification to health national administration is rarely
      systematic, in particular with isolated elevation of hepatic enzymes, and even
      more rarely published in international reviews. Nevertheless, according to the
      present data available in the literature, systematic and regular hepatic survey
      does not seem necessary in absence of risk factors. As for other side effects,
      which may occur more or less rapidly, great advantages may be obtained from
      psycho-education programs associating the patients in order to detect the first
      symptoms. Because little long-term hepatic follow-up comparing AAD is available,
      controlled studies should be carried out to precise the frequency and the risk
      factors (covariables) to prevent hepatitis outcome.

PMID- 12506268
TI  - [Minimizing the risks associated with QTc prolongation in people with
      schizophrenia. A consensus statement by the Cardiac Safety in Schizophrenia
      Group].
AB  - Schizophrenia is one of the most debilitating mental illnesses, complicated by an
      increased incidence of suicide amongst patients compared with the general
      population. A recent report has also demonstrated a 33% increase in -relative
      risk of death associated with circulatory disease, indicating that the latter may
      be a more critical factor than either suicide or accidental death in this
      population. Indeed, the average life expectancy of a person with schizophrenia is
      currently approximately a decade less than that of the general population.
      Additionally, it has been shown that in over 50% of people with schizophrenia,
      there is a reduction in their chance of reaching psychosocial goals. Since the
      arrival of the first antipsychotic drugs in the middle of the last century, the
      outlook for patients with schizophrenia has improved markedly. In particular, the
      introduction of the new generation (atypical) class of antipsychotic agents in
      the 1980s and 90s has resulted in a significant reduction in the incidence of
      violent and aggressive episodes in treated patients. A better side-effect profile
      of these drugs, especially reduced extra pyramidal symptoms (EPS), has resulted
      in improved patient outcomes and the possibility of good long-term control of the
      disorder. However, while the introduction of antipsychotic agents has undoubtedly
      revolutionised the prognosis for patients with schizophrenia, these medications
      are not without their own problems. One of the concerns to emerge over the last
      fifteen years is unpredictable, sudden and unexplained death in patients taking
      antipsychotic drugs. The cause of sudden death in this population is
      controversial and the role of drugs is not clear. People with schizophrenia also
      appear to be at higher risk of cardiovascular disease compared with the general
      population. Many factors may play a role in this including a higher prevalence of
      smoking, poorer diet, more sedentary lifestyle and a greater likelihood of
      alcoholism and substance abuse. However, it is possible that the impact of
      adverse effects on the cardiovascular system related to certain antipsychotic
      drug use may well increase the prevalence of mortality and morbidity due to
      cardiovascular events and may also play a significant role in the reduced life
      expectancy of the patient with schizophrenia. The range of mechanisms whereby
      antipsychotic drugs can influence cardiovascular function is very broad and
      includes: receptor blockade; conduction disturbance (eg bundle branch block);
      delayed ventricular repolarisation (prolonged QTc interval); left ventricular
      dysfunction; sinus node abnormalities; myocarditis; postural hypotension;
      polydipsia-hyponatremia syndrome; weight gain; glucose intolerance. Of these, QTc
      interval prolongation, with the risk of progression to the potentially fatal
      ventricular tachyarrhythmia Torsades de Pointes (TdP), is of particular concern
      as this arrhythmia is unpredictable and difficult to manage. Coupled with these
      clinical concerns are regulatory issues regarding several compounds that have
      received warnings or been withdrawn from the market. Recently, there has been no
      clear guidance for psychiatrists regarding QTc interval prolongation and TdP.
      This document seeks: 1) to explore drug-induced ventricular arrhythmias with
      particular emphasis on QTc interval prolongation as a warning of increased
      vulnerability, 2) to provide guidelines on the therapeutic management of the
      patient with schizophrenia to minimize the risk of iatrogenic cardiotoxicity.
      Several guidance documents have previously been published in this area including
      the report published by the UK Working Group of the Royal College of
      Psychiatrists' Psychopharmacology Sub-Group in 1997, and the policy document on
      the potential for QTc prolongation and proarrhythmia by non-antiarrhythmic drugs
      published in June 1999 under the auspices of the European Society of Cardiology.
      This document seeks to supplement currently published guidelines.

PMID- 12506269
TI  - [A case report of mania precipitated by use of DHEA].
AB  - Dehydroepiandrosterone (DHEA) and its sulfate ester metabolite (DHEA-S) are
      precursors to testosterone and, to a lesser extent, to estrogen, and, for both
      sexes, they are produced in the adrenal cortex. They are among the most abundant
      steroids in the human body, yet their physiological roles remain unknown. DHEA
      and DHEA-S appear to have diverse biochemical activities, including actions
      within the central nervous system. So DHEA is produced in the central nervous
      system as well as the human adrenals and is present in the brain, concentrated in
      limbic regions, in levels much higher than other steroids. DHEA has been
      postulated to function as an excitory neuroregulator, antagonizing g-aminobutyric
      acid transmission. The main characteristic of DHEA is that its level of
      concentration in plasma varies throughout life, such level being low during the
      early childhood and after the age of 60 years. Adrenal production and serum
      concentrations of DHEA are then known to peak between ages 25 and 30 years and
      thereafter decrease with age, severe illness and chronic stress. The decrease of
      DHEA over time would appear to be responsible for morbidity related to aging
      process. Previous reports have found low levels of DHEA in association with
      physical and with frailty in the elderly (immunosenescence, increased incidence
      of osteoporosis, atherosclerosis and cancer, decreased cognitive functions and/or
      well-being). As it has been touted as a fountain of youth and a sexual tonic and
      promoted for a variety of illnesses associated with aging, DHEA is widely
      available over all the United States (since 1994) as a dietary supplement. In
      France, as a result of a massive advertising campaign, DHEA is already the
      subject of a widespread use and a growing demand although it has not yet been
      approved by the relevant authorities for sale as drug to the public. In practice,
      DHEA is prescribed and delivered under the sole responsibility of both doctor and
      chemist who ascertain the benefit-risk ratio and the quality of the product. DHEA
      may then be purchased on the internet or in the form of magistral preparations
      delivered on the basis of such prescription. Accordingly, there is little
      information or data on efficacy, drug interactions, results of long-term use,
      abrupt discontinuation or potential adverse effects related to the use of DHEA.
      We report a case of mania possibly precipitated by the use of high doses of DHEA
      (150-200 mg/day at the time of presentation) during several weeks in a 68 years
      old man who had already been hospitalized for an acute mania many years ago.
      Although, in this case, the patient suffered a bipolar diathesis in the past,
      oral DHEA may have played a role in the induction of his acute manic episode.
      Further research is required to assess the mood effects of DHEA, including its
      potential risk for patients with bipolar disorder.

PMID- 12506270
TI  - [Neutropenia in a patient treated with clozapine in combination with other
      psychotropic drugs].
AB  - Clozapine is an atypical antipsychotic known for its efficacy in refractory
      schizophrenia. However, according to different epidemiological studies clozapine
      can induce neutropenia in less than 3% of patients and may represent a major
      problem for the management of treatment-resistant patients not responding to
      conventional or other atypical antipsychotics. Recently, a few case of
      neutropenia have been reported following the addition of other medications to
      clozapine, notably paroxetine, risperidone, trimethoprim-sulfamethoxazole and
      erythromycin. In our report we present the case of Mr A., a 40-year-old Caucasian
      patient with a 20-year history of paranoid schizophrenia. After numerous trials
      with conventional antipsychotics, partial remission of psychotic symptoms was
      obtained with clozapine. Over the past eight years during his treatment with
      clozapine, the patient presented 2 episodes of neutropenia. The first episode
      came five years after starting clozapine and was attributed to the addition 6
      weeks earlier of haloperidol (2 mg/day) to clozapine (250 mg/day) and divalproex
      (1,500 mg/day). Recently, one week after the addition of risperidone (2 mg/day)
      to clozapine (550 mg/day), leukocytes count dropped from 12 100/mm(3) to 5
      700/mm(3) and neutrophils from 7 400/mm(3) to 900/mm(3). The patient was also
      taking haloperidol (4 mg/day), methotrimeprazine (35 mg/day), procyclidine (5
      mg/day) and valproic acid (1,500 mg/day). Twelve days after discontinuation of
      risperidone, leukocytes and neutrophils count increased to 11,100/mm(3) and
      6,300/mm(3) respectively while the treatment with clozapine was continued. The
      first eighteen weeks of treatment represent the period where the risk of
      neutropenia is the highest. In our patient neutropenia occurred 5 and 7 years
      after starting clozapine. It is proposed that the two neutropenic episode were
      precipitated by adding respectively haloperidol and risperidone to clozapine.
      Also, divalproex can potentially cause a decrease in white blood cell count and
      may have contributed to the two neutropenic episode. It is suggested that drug
      interactions may be responsible for neutropenia in clozapine treated patients and
      that clozapine should not necessarily be discontinued in the presence of
      neutropenia. Also we propose that hematological surveillance should be done on a
      weekly basis for 4 to 6 weeks following the addition of psychotropic drugs known
      for their potential to cause neutropenia when associated with clozapine.
      Therefore polypharmacy may contribute to cause neutropenia in clozapine treated
      patients and that discontinuation of an antipsychotic should be done before
      introducing another one.

PMID- 12506271
TI  - Pediatric environmental health.

PMID- 12506273
TI  - A 12-year, prospective study of extraocular muscle imaging in complex strabismus.
AB  - INTRODUCTION: Diagnostic imaging by magnetic resonance imaging (MRI) or computed
      x-ray tomography (CT) has become the standard of care in many medical fields.
      Clinical imaging of the extraocular muscles (EOMs) can now provide insight into
      some causes of strabismus, in some cases challenging traditional concepts of
      etiology and suggesting alternative treatments. METHODS: Between 1990 and 2001,
      62 orthotropic volunteers and 261 strabismic patients underwent orbital imaging
      under a prospective protocol. Surface coil MRI was performed with fixation
      control with slice thickness of 1.5 to 3 mm; CT was performed with 1-mm slice
      thickness. Images were correlated with ophthalmological examinations. RESULTS:
      MRI was performed in 267 and CT in 56 subjects. Comparison with normal orbits
      commonly demonstrated abnormalities of EOM size or location in strabismic
      patients. These included absence (5 patients) or atrophy (33 patients) of the
      superior oblique (SO) muscle in SO palsy; abnormalities of the trochlea or SO
      tendon in Brown's syndrome (8 patients); heterotopy of the rectus pulleys
      associated with incomitant strabismus (46 patients), including instability of
      pulleys (9 patients); trauma to rectus EOMs (16 patients); atrophy of the lateral
      rectus (10 patients), inferior rectus (4 patients), medial rectus (4 patients),
      superior rectus (4 patients), and inferior oblique (1 patient) muscles; and EOMs
      disinserted by scleral buckles (3 patients). EOM abnormalities correlated closely
      with clinically abnormal patterns of ocular motility. CONCLUSIONS: With the
      appropriate technique, EOM imaging is a valuable adjunct in clinical evaluation
      of complex strabismus. Because imaging can provide unique information unavailable
      from the clinical examination alone, it should be performed when indicated to
      evaluate patients with strabismus more complex than concomitant esotropia and
      exotropia.

PMID- 12506274
TI  - Axial myopia associated with dense vitreous hemorrhage of the neonate.
AB  - BACKGROUND: Various forms of visual deprivation during infancy have been shown to
      cause axial myopia. Although infantile vitreous hemorrhage is associated with
      myopic progression, it is unknown whether this aberrant development is refractive
      or axial. The primary objectives of this study were to investigate this abnormal
      myopic development and to determine what duration of dense vitreous hemorrhage is
      sufficient to cause significant amblyopia in neonates. METHODS: Four infants with
      dense unilateral vitreous hemorrhages in the first weeks of life underwent serial
      evaluations of the posterior segment, refractive error, and A-scan
      ultrasonography. RESULTS: Three of the 4 infants underwent successful lens
      sparing vitrectomy between 3 and 6 weeks after the onset of the hemorrhage, and
      all 3 developed axial myopia and dense amblyopia during a mean follow-up of 29.7
      months (range, 16 to 38 months). At the most recent follow-up examination, the
      mean myopic error of the 3 eyes that required surgery was -11.42 D with a mean
      ocular axial length difference of 3.45 mm between the affected and the unaffected
      eyes. The fourth child had a dense hemorrhage soon after birth that cleared by 11
      days of age. Although this patient developed amblyopia and a mild myopic error of
      the involved eye, there was no significant increase in axial length. CONCLUSIONS:
      Dense hemorrhages persisting in the neonatal vitreous for 4 weeks or longer
      appear to cause axial myopia and severe amblyopia. Surgical intervention before
      this time should be considered to avert deprivation amblyopia and to retard axial
      myopia.

PMID- 12506275
TI  - Up-slanting palpebral fissures and oblique astigmatism associated with A-pattern
      strabismus and overdepression in adduction in spina bifida.
AB  - PURPOSE: To describe the spectrum of adnexal and ophthalmologic features in spina
      bifida. METHODS: A retrospective review of the medical records of 73 patients was
      conducted. Data concerning ocular motility, palpebral fissure orientation,
      presence and axis of astigmatism, visual acuity, amblyopia, and stereopsis were
      analyzed. RESULTS: Forty-three (59%) of the 73 patients had strabismus: 28 (65%)
      had esotropia, 12 (28%) had exotropia, and 3 (7%) had orthotropia in primary gaze
      and a significant A-pattern. Of the strabismic patients, 20 (47%) had an A
      pattern, of which 13 (65%) demonstrated overdepression in adduction. Twenty-seven
      (84%) of the 32 patients with documented palpebral fissure orientation had
      exaggerated up-slanting palpebral fissures. Forty-nine (77%) of 64 patients
      exhibited astigmatism greater than 0.75 D in at least 1 eye, with a mean power of
      1.6 D. The axis of cylinder was oblique in 76% of these patients. The astigmatic
      axis was consistently oriented perpendicular to the eyelid fissure orientation in
      the group of patients with up-slanting palpebral fissures, with the mean axis of
      cylinder being incyclorotated (OD axis, 77; OS axis, 108). Up-slanting palpebral
      fissures were associated with a 15-fold increased chance that the axis of
      cylinder would be incyclorotated (P =.07, chi-square test). An orbital computed
      tomographic (CT) scan of a spina bifida patient with A-pattern esotropia,
      overdepression in adduction, and up-slanting palpebral fissures demonstrated
      significant incyclorotated extraocular muscle pulley heterotopy. CONCLUSIONS:
      Exaggerated up-slanting palpebral fissures are a prominent feature in spina
      bifida. Up-slanting palpebral fissures in spina bifida patients are associated
      with incyclorotated oblique astigmatism, A-pattern strabismus, and overdepression
      in adduction. These associations might be related to an anomaly of orbital
      skeletal or extraocular muscle pulley development. Further prospective study is
      encouraged.

PMID- 12506276
TI  - Initial nasolacrimal duct probing in children under age 5: cure rate and factors
      affecting success.
AB  - AIMS: To evaluate the success rate of initial probing and the factors affecting
      the success rate for congenital nasolacrimal duct obstruction (CNLDO)in children
      under the age of 5 years. METHODS: In a prospective uncontrolled interventional
      case series, 207 eyes from 161 consecutive patients with CNLDO underwent
      nasolacrimal duct probing under brief general anesthesia. Based on exclusion
      criteria, 180 eyes from 139 patients were included in the study. Diagnoses were
      made according to the patients' histories, clinical examinations, and modified
      dye disappearance tests. The state of the punctum, the canaliculus, the sac, and
      the nasolacrimal duct were recorded. The main outcome measure was the complete
      disappearance of tearing and discharge in the affected eye. The patients were
      followed at 1 week, 1 month, and 3 months postoperatively. RESULTS: The age range
      was 5 to 60 months (mean, 19.1 +/- 11.2 months). The cure rates were 92% in the
      first year, 84.5% in the second year, 65% in the third year, and 63.5 in the
      fourth and fifth years of age. The patient's age, nonmemberanous CNLDO, and
      canalicular stenosis were correlated with the success of initial nasolacrimal
      duct probing (P <.05). CONCLUSIONS: Based on the results, simplicity of probing,
      and absence of significant complications, initial nasolacrimal duct probing is
      advised up to the age of 5 years. Increasing age, nonmembranous CNLDO, and
      canalicular stenosis increase the failure rate (P <.05).

PMID- 12506277
TI  - Dilation probing as primary treatment for congenital nasolacrimal duct
      obstruction.
AB  - PURPOSE: Recent studies have suggested that simple nasolacrimal duct (NLD)
      probing can be an effective primary surgery for congenital NLD obstruction
      regardless of age. The success of balloon dilation after failed NLD probing
      suggests that maximally enlarging the passage through the NLD system may enhance
      the success of simple NLD probing. This study used sequential probing with
      modified, taper-tip probes to evaluate whether maximally enlarging the
      nasolacrimal duct can effectively treat congenital NLD obstructions in all age
      groups. METHODS: Under general anesthesia, each obstructed NLD system was
      sequentially probed with larger diameter NLD probes until firm resistance
      prevented the passage of any larger probe size. Successful treatment was defined
      as a negative dye-disappearance test 2 weeks after probing and the absence of
      tearing symptoms at last contact. RESULTS: A retrospective chart review
      identified 40 patients ages 6 to 32 months (average, 17.7 months) who underwent
      the sequential probing procedure. Sequential NLD probing was successful in 66
      (92%) of 72 eyes. Of the failures, both eyes in a 15-month-old patient with
      Down's syndrome had tight, anomalous NLD systems. In the remaining 4 eyes, 2 had
      resolution of symptoms but partially positive dye-disappearance tests, and 2
      underwent successful repeat sequential NLD probing. Subdividing by age, 27 (100%)
      of 27 obstructed NLD systems were treated successfully in patients older than 18
      months compared with 39 (87%) of 45 in younger patients. CONCLUSIONS: Sequential
      NLD probing to maximally enlarge the NLD system has a high rate of success in all
      children. Age does not appear to have an impact on success of probing.

PMID- 12506278
TI  - Levodopa-carbidopa with occlusion in older children with amblyopia.
AB  - PURPOSE: To study the role of levodopa-carbidopa in supplementing occlusion
      therapy in older children with strabismic or anisometropic amblyopia. METHODS: A
      clinical study was performed on 40 amblyopic children (19 strabismic and 21
      anisometropic), 6 to 18 years old (mean age, 10.9 years). They received an
      average dose of 1.86 mg/kg/day (1.33-2.36 mg/kg/day) of levodopa and carbidopa
      (4:1 ratio) or a placebo in 3 divided doses over a 4-week period, combined with
      full-time occlusion. The occlusion was continued for the study duration of 3
      months. Early Treatment Diabetic Retinopathy Study visual acuity charts and
      Cambridge low-contrast gratings for contrast sensitivity (CS) were used to assess
      visual functions. Tolerance and compliance with occlusion and capsule consumption
      were assessed. RESULTS: Visual acuity of the nonamblyopic eye did not deteriorate
      during the study in either group. CS decreased by 22 units in the levodopa group
      and increased in the placebo group by 53 units at the first month. The CS in the
      levodopa group recovered later by the third month of follow-up. Both the levodopa
      and the placebo groups showed significant improvement in visual function in the
      amblyopic eye (P <.001). Overall changes in logarithm of minimum angle of
      resolution values and CS in the amblyopic eyes were similar in both groups (P
      >.05). Strabismic and anisometropic amblyopes did not behave differently. Drug
      tolerance, occlusion compliance, and capsule ingestion compliance were similar
      between the groups, with no significant side effects. CONCLUSIONS: Clinically,
      levodopa supplementation does not offer any advantage over occlusion alone.
      Moreover, the risk of occlusion amblyopia could increase with the use of drugs
      like levodopa that might affect the plasticity of the visual cortex.

PMID- 12506279
TI  - Time of onset of uveitis in children with juvenile rheumatoid arthritis.
AB  - BACKGROUND: Recently, it has been advocated to decrease the frequency of eye
      examinations to screen for uveitis in children with juvenile rheumatoid arthritis
      (JRA) because of the low yield of positive findings after an initial normal eye
      examination. This study was undertaken to determine the time interval for the
      development of uveitis after the diagnosis of JRA and to further describe
      patients who develop uveitis related to JRA. METHODS: This was a retrospective
      chart review of all patients with JRA examined by either of 2 pediatric
      ophthalmologists from August 1984 to June 2001. All patients were also under the
      care of the Pediatric Rheumatology Division at Schneider Children's Hospital. Age
      of diagnosis of JRA, disease onset subtype of JRA, antinuclear antibody titers,
      age of diagnosis of uveitis, and complications from uveitis were recorded.
      RESULTS: One hundred fifty eight patients with JRA had eye examinations; 39 (25%)
      developed uveitis. Sixteen patients had uveitis on the initial eye examination,
      and 23 subsequently developed uveitis. When uveitis was absent at the initial eye
      examination, the mean time to develop it was 20 months (range, 4-81 months).
      CONCLUSIONS: A normal initial eye examination does not preclude the development
      of uveitis in patients with JRA. We recommend continuing the current standards of
      ophthalmologic examinations to screen for uveitis in children with JRA as
      prescribed by the Section on Rheumatology and Ophthalmology of the American
      Academy of Pediatrics.

PMID- 12506280
TI  - Accommodation to large disparity stereograms.
AB  - PURPOSE: The purpose of this study was to test whether observers would show
      accommodation changes to depth depicted in large disparity stereograms and
      whether the amount of accommodation was related to the amount of depth seen in
      the stereograms. Previous studies have shown small accommodation changes to depth
      depicted in stereograms. We tested a larger range of depths than previously
      investigated and also asked observers to judge the depth depicted in the
      stereogram, because a previous study had suggested that this might be an
      important factor. METHODS: All our observers had emmetropia. Accommodation was
      measured with a Canon Autoref R-1autorefractor as an observer viewed a depthful 4
      by-4 cm planar target set against a 20-by-20 cm planar background 57 cm from the
      observer. The target was presented at a range of depths, -8 to +8 cm, either in
      stereogram stimuli or real stimuli. Each observer also made depth judgments of
      stereogram targets, after training with real targets. We also recorded the time
      taken for each observer to discern the depicted depths in stereograms. RESULTS:
      The accommodation shown by all observers (n = 9) to stereogram targets was
      significant but was on average about 60% of that predicted. There were individual
      differences in the accommodation an observer showed to stereogram targets, but
      this was not related to the amount of depth the observer saw in the stereogram.
      CONCLUSIONS: Accommodation changes did occur to stereogram targets, but these
      were generally less than predicted and also less than those shown for real
      targets. Possible reasons for these findings and the implications for the use of
      stereograms in clinical tests are discussed.

PMID- 12506281
TI  - Infantile spasms as a cause of acquired perinatal visual loss.
AB  - BACKGROUND: Visual abnormalities have been described in patients with infantile
      spasms (IS), an epileptic syndrome of early childhood. METHODS: We report on 3
      children who exhibited cortically mediated visual regression in association with
      the development of IS. RESULTS: In 1 patient, loss of visual behavior was the
      presenting complaint. In all patients, visual behavior improved with treatment of
      seizures. CONCLUSIONS: IS are a potentially treatable cause of cortically
      impaired vision in early childhood. Because visual behavior might improve when
      the seizures are treated, patients should be referred appropriately.

PMID- 12506282
TI  - Visual evoked potentials in successfully treated strabismic amblyopes and normal
      subjects.
AB  - PURPOSE: To assess electrophysiological recovery in successfully treated
      strabismic amblyopes. METHODS: Pattern reversal visual evoked potentials were
      recorded from 11 successfully treated strabismic amblyopes 7 to 11 years of age
      and 10 age-matched normal children using 12.5' and 50' checks. RESULTS: Nine
      amblyopic eyes had recovered to a Snellen acuity of 6/6 or better, and the
      remaining 2 were 6/9 after patching. Comparison between the amblyopic and the
      fellow eyes showed significantly lower P100 amplitude for the amblyopic eyes with
      small checks (difference -16.7%; P <.02) and significantly longer latency with
      larger checks difference (+5.0%; P <.02). The P100 latencies to stimulation of
      both the amblyopic and fellow eyes by 12.5' checks were markedly longer than in
      normal subjects (amblyopic eye, +11.7%, P <.0001; fellow eye, +7.7% P <.002).
      CONCLUSIONS: Successfully treated amblyopic eyes showed significantly longer
      latency than did normal eyes with small check stimulation. However, the
      nonamblyopic fellow eyes also showed significantly longer latency than did normal
      eyes, suggesting altered central processing.

PMID- 12506283
TI  - Grating acuity in albinism in the first three years of life.
AB  - PURPOSE: To compare grating acuity of children 1 to 3 years old with albinism
      with that of age-matched normal children, and to determine whether ocular pigment
      and macular structure are predictive of grating visual acuity. METHODS: In this
      retrospective cross-sectional review of 64 children with albinism, binocular
      grating acuity was measured with Teller acuity cards at 1, 2, or 3 years of age.
      Iris transillumination and macular transparency were graded according to
      published scales. The presence or absence of macular melanin pigment and a
      rudimentary foveal reflex were assessed with direct and indirect ophthalmoscopy,
      respectively. RESULTS: Mean grating acuities of the children with albinism at
      ages 1 (2.48 cycles (cy)/degrees), 2 (3.62 cy/degrees), and 3 (5.87 cy/degrees)
      were 2.3, 2.1, and 1.7 octaves lower than published norms (all with P <.001). The
      studied variables did not correlate with visual acuity except for macular
      transparency at age 2 (r = 0.40; P =.030). CONCLUSIONS: Grating acuity can be
      used to assess the reduction in visual function in albinism in the first 3 years
      of life. However, grading of iris transillumination and macular transparency and
      recognition of an annular reflex or macular melanin do not consistently correlate
      with the development of vision measured by grating acuity.

PMID- 12506284
TI  - Lateral rectus muscle avulsion by a cat scratch.

PMID- 12506285
TI  - Cone-rod retinal dystrophy and Duane retraction syndrome in a patient with
      achondroplasia.

PMID- 12506286
TI  - Relevance of some of the theories of Ibn Khaldoun in his "Al Muqaddimah" to
      contemporary medicine. A personal interpretation.
AB  - The subjects in this paper include Ibn Khaldoun's thoughts on writing, and their
      implications on today's medical writing. This paper discusses why people write,
      plagiarism, "Original" and "Copied' writings and where history writing goes wrong
      and how this can be applied to Medical writing today. The paper also discusses
      the nature of Science and Knowledge as viewed by Ibn Khaldoun, the anatomy of
      intelligence, types of thought processes, and effects of environment and
      craftsmanship on intellect. Ibn Khaldoun's definition of the "Medical" profession
      and its social standing is discussed as well as his emphasis of the importance of
      exercise, diet and climate on healthy living. Ibn Khaldoun has clear and advanced
      concepts on education and methodology of education. He emphasizes 3 stages of
      coaching, and the importance of travel in consolidating and clarifying knowledge
      attainment. He abhors coercion as a method of educating the young. Developing the
      interest of the pupil in the art he is studying, is thought by Ibn Khaldoun to be
      the central theme of good education. Relevance of all this to contemporary
      medical education is discussed. Ibn Khaldoun has fascinating ahead-of-time views
      on the influence of peer pressure and what is now known as "Emotional
      Intelligence" and he rejects the idea that intelligence is ethnically determined.
      Instead, he emphasizes the environmental, social and craftsmanship influence on
      human behavior. He stresses that the method of education has a lot to do with the
      "apparent" intelligence or "stupidity" of pupils.

PMID- 12506287
TI  - Current surgical treatment of Parkinson's disease.
AB  - There has been a renaissance in the surgical management of Parkinson's disease.
      This has been due to long-term effects of levodopa and a better understanding of
      the basal ganglia and its circuitry. Ablative surgery and neurostimulation are
      the only realistic surgical options at present. Although surgical treatments,
      such as ablation and stimulation are effective, they are not useful for stopping
      the progression or restoring the system. Neural transplantation helps restore the
      system by using a number of techniques. Targets mostly used are in the thalamus,
      globus pallidus and subthalamic nucleus. A number of factors must be considered
      including patient's age, disability and his wishes. Globus pallidus stimulation
      might be preferable for patients who suffer from dyskinesia as a major source of
      disability. Pallidotomy might be appropriate in cases where frequent stimulator
      adjustments are impractical. Subthalamic nucleus stimulation is more suitable for
      patients with significant off periods and in younger patients in whom it may be
      desirable to maintain intact circuitry. Fetal neural transplantation, stem cell
      transplantation, xenotransplantation, adrenal medullary transplantation and
      transplantation of genetically engineered cells are at various stages of
      development and research. Ethical issues surrounding these process are likely to
      arouse strong emotions and have to be carefully considered.

PMID- 12506288
TI  - Research and research activities in a university in Eastern Saudi Arabia.
AB  - OBJECTIVES: The purpose of the present study was to obtain the views of faculty
      members regarding various aspects of scientific research, which is one of the
      essential functions of a University. METHODS: A cross-sectional study was
      conducted in the College of Medicine, King Faisal University, Dammam, Kingdom of
      Saudi Arabia, between January and June 2001, using a standardized questionnaire
      to obtain the views of faculty members in both basic and clinical departments on
      issues related to scientific research. The questionnaire consisted of 41 items
      and the responses were assessed on a 5 point scale. The variables included
      specified objectives for research by administration, quality of research, process
      of application for funding, available facilities for research, constraints to
      meaningful scientific research and mechanisms that would enhance its quality.
      RESULTS: The response rate was 67% (74 of the total available 110): Professors
      22, Associate Professors 27, Assistant Professors 23 and Lecturers 2 in 24
      departments (6 basic sciences, 18 clinical sciences). The number of completed
      research projects was judged inadequately by 50 (68%), and 31 (42%) thought the
      quality could be improved upon. The process of the application for funding was
      cumbersome. The major identified constraints were inadequate infrastructure,
      additional administrative duties (89%) and teaching schedule overload (82%). The
      major strategies suggested to enhance the quality of research included
      simplifying the process for application for research (approval and funding),
      provision of defined quality time for faculty members to engage in research and
      the establishment of adequate support and infrastructure facilities. CONCLUSIONS:
      Most faculty members aspire for a higher quality of biomedical research. The
      following were identified strategies to improve research goals and quality:
      Provision of starting seedling packages for new faculty members, simplifying
      research application processes, establishing efficient and adequate
      infrastructures, and providing protected research time.

PMID- 12506289
TI  - Herbal medicine in the treatment of diabetes mellitus.
AB  - OBJECTIVES: The use of herbs is common among diabetics. The aim of this study is
      to determine the prevalence of the use of herbs among diabetics and which herbs
      are used. Additionally, to investigate the effect of some demographic
      characteristics on the use of such herbs. METHODS: A cross sectional study was
      conducted on diabetic patients attending the outpatient clinics in 4 major
      hospitals in Riyadh, Kingdom of Saudi Arabia. These were: King Khalid University
      Hospital, King Abdul-Aziz University Hospital, Prince Salman Hospital and Riyadh
      Medical Complex over a 3-month period which started in September 1999. Patients
      were interviewed by trained medical students through a predesigned questionnaire
      that contains items that are related to diabetes and the use of herbs by
      diabetics. RESULTS: Two hundred and ninety six diabetic patients out of 300 were
      interviewed giving a response rate of 98.6%. Fifty-one subjects (17.4%) reported
      using some form of herbs. The commonest herbs used were myrrh, black seed,
      helteet, fenugreek and aloes. Approximately 73% of herbs users did not inform
      their doctor regarding their use of herbs. No statistically significant
      relationship existed between demographic characteristics and the use of herbs.
      CONCLUSION: The use of herbs is not rare among diabetic patients. Doctors caring
      for diabetic patients should encourage them to talk regarding the use of herbs as
      it may effect the outcome and the management of their disease.

PMID- 12506290
TI  - Blood sugar control, ophthalmology referral and creatinine level among adult
      diabetic patients in primary health care, Riyadh, Saudi Arabia.
AB  - OBJECTIVES: The objectives of the study were to review the blood sugar levels,
      duration of illness, referral to the Eye Clinic for Ophthalmology assessment, and
      basic renal function by creatinine level among adult diabetic patients in primary
      health care in Riyadh, Kingdom of Saudi Arabia. METHODS: A retrospective study of
      medical records for diabetic adult patients at different age groups, of both sex,
      in 6 primary health care centers in Riyadh, Kingdom of Saudi Arabia was carried
      out during the period from August 2000 to April 2001. RESULTS: The results of
      this study show that the duration of diabetes were less than 10 years among 67%
      of diabetic adult patients, and fasting blood sugar levels were more than 10
      mmol/L among 49.2% of diabetic adult patients. Glycosylated hemoglobin were
      recorded in 0.4% of medical records which, might be due to lack of accessibility
      for this laboratory test in the selected primary health care centers. Thirty
      point seven percent of diabetic patients were referred to ophthalmologist, and
      74% of diabetic patients had creatinine level <150 mmol/L. CONCLUSIONS: Improving
      the blood sugar control and shared care with ophthalmologists are important steps
      to improving the quality of diabetic care in primary health care.

PMID- 12506291
TI  - Lichenoid dermatosis. A clinical and histopathological study.
AB  - OBJECTIVES: A distinctive skin problem has been observed for the last 10 years
      that appeared on the neck of a young adult. This encouraged us to conduct this
      study, to evaluate its clinical and histopathological picture. METHOD: Thirty
      patients were studied in the Department of Dermatology, Baghdad Teaching
      Hospital, Iraq during a one-year period from November 1998 through to November
      1999. There were 29 males and a female, their ages ranged from 11-50 years (mean
      25 years). Patients complained of rash on the back and sides of the neck, they
      were fully interrogated and examined and skin biopsy was carried out in 10
      patients. RESULTS: The study showed that this disease has well defined clinical
      pictures, which affect young males mainly and appeared in summer time. The rash
      was located mostly on the back of the neck; it had dark-red to red-violeceous,
      rounded to oval, single or multiple plaques. The rash was mainly asymptomatic a
      part from appearance. The histopathological picture has many similarities with
      that of lichen planus actinicus, but with striking increased vascularity of the
      dermis. CONCLUSION: From the clinical and histopathological study, this skin
      problem deserve its own name lichenoid dermatosis, which was induced by solar
      radiation and has many similarities with lichen planus actinicus and could be
      confused with lichen simplex chronicus.

PMID- 12506292
TI  - Laparoscopic versus open appendectomy in females with a clinical diagnosis of
      appendicitis.
AB  - OBJECTIVE: Appendectomy can be performed using either a laparoscopic technique
      (LT) or an open technique (OT). We compared the following items operative,
      anesthesia, length of stay, post-operative pain, medicine, wound healing, days to
      return to normal activity in both groups. METHODS: This study was carried out at
      King Fahad Hospital, Hofuf, Al-Hassa, Kingdom of Saudi Arabia, from January 1999
      to April 2000. We randomly assigned 60 female patients to appendectomy by LT or
      OT. The 2 groups were compared concerning demographic data. The differences were
      considered statistically significant at a P value < 0.05. RESULTS: The open group
      had shorter anesthesia and operative time (68, 50 versus 85, 65 minutes). The
      laparoscopic group had a significant reduced postoperative narcotic requirement
      (P<0.05), quicker reintroduction of diet and quicker return to normal activity.
      CONCLUSION: Laparoscopic appendectomy in female patients with clinical diagnosis
      of appendicitis is the procedure of choice for the diagnosis and the management
      of acute appendicitis.

PMID- 12506293
TI  - A study comparing different approaches in managing neck nodes in early carcinoma
      of the tongue.
AB  - OBJECTIVE: To evaluate elective neck treatment in patients with early stage (T1-2
      negative neck node [N0]) squamous cell carcinoma of the oral tongue. METHODS: The
      medical records of all patients with early stage (T1-2 N0) of oral tongue cancer
      at the King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of
      Saudi Arabia, between January 1980 and December 1997, were identified and
      retrospectively reviewed. RESULTS: Our cohort consisted of 93 patients: 45 males
      and 48 females, with a median age of 60 years. All patients received treatment
      with curative intent. Partial glossectomy was carried out, except for 8 patients
      who underwent tongue brachytherapy. The neck was observed in 29 patients, 36 were
      treated by modified neck dissection, and 28 by elective neck irradiation. With a
      median follow-up of 62 months, 29 patients had documented neck node recurrence.
      Ninety six percent (28/29) of recurrences occurred within 22 months from
      treatment completion. The 5 year actuarial event free survival with regard to
      nodal relapse in observed was 59%, dissected was 79% and irradiated neck was 63%.
      Our results showed a trend toward better neck node control in patients managed by
      elective neck dissection compared to those observed (p=0.07) or receiving
      elective neck irradiation (p=0.18). Tumor thickness of more than 10 mm was
      associated with increased risk of nodal relapse (p=0.0004). Neck node recurrence
      has a poor prognosis with a 5 year disease specific survival of 16%. CONCLUSION:
      A trend for higher neck control was observed after neck dissection in patients
      with T1-2 N0 squamous cell carcinoma of the oral tongue. Elective neck dissection
      should be considered particularly for patients with tumor thickness of more than
      10 mm.

PMID- 12506294
TI  - Plication darn for the repair of inguinal hernia. A university hospital
      experience.
AB  - OBJECTIVE: Recurrence rate in inguinal hernia repair is the main concern of both
      the surgeon and patients. The aim of this study is to evaluate the outcome in
      patients undergoing open inguinal hernia repair by using muscle fascial plication
      and nylon darn. METHODS: This technique was performed in 2 University hospitals
      within the Kingdom of Saudi Arabia. King Abdul-Aziz University Hospital and King
      Khalid University Hospital, Riyadh, for a period of 23 years, October 1978
      through to October 2001, on a total of 600 patients. RESULTS: The total number of
      patients was 654 these were all male. The same repair was performed in elective
      cases, in acute emergency and for both direct and indirect inguinal hernia.
      Patients suffering from chronic cough are referred to a pulmonologist for
      treatment before surgery. Follow-up was for a period of 10 years thereafter by
      phone communication. Fifty-four patients were excluded from the study as they
      failed to attend for follow up after the 3rd year. Six hundred patients underwent
      619 repairs. Post operative pain was controlled by pethidine in the first 24
      hours, thereafter by paracetamol tablets. Patients were advised to return to
      normal activity after 3/52. No heavy weight lifting before 3-4 months. Recurrence
      occurred in one case. CONCLUSION: Muscle fascial plication combined with nylon
      darn is a good operation for the repair of inguinal hernia.

PMID- 12506295
TI  - Role of ultrasonography, computed tomography and diagnostic peritoneal lavage in
      abdominal blunt trauma.
AB  - OBJECTIVE: To compare the diagnostic accuracy of diagnostic peritoneal lavage
      (DPL), ultrasonography and computed tomography in the management of blunt
      abdominal trauma. METHODS: A retrospective review of the charts of 233 patients
      with blunt abdominal trauma necessitating admission to Riyadh Medical Complex,
      Riyadh, Kingdom of Saudi Arabia was carried out over a 2 year period (January
      2000 to December 2001). The diagnostic yields of DPL, ultrasound and computed
      tomography were analyzed. The results were compared with findings on subsequent
      laparotomy or ultimate outcome, which continued in hospital observation and
      conservative management. RESULTS: Mean age was 23 years and 79% patients were
      male. Road traffic accident remained the most common cause (70%) and 56% patients
      had multisystem injuries. The sensitivity for DPL, ultrasound and computed
      tomography scans was found to be 98%, 96% and 98% with an overall accuracy rate
      of 92%, 95% and 99%. Diagnostic peritoneal lavage showed false positive results
      with retroperitoneal injuries and missed one small bowel injury and a pancreatic
      injury, and resulted in one catheter related bowel injury. Computed tomography
      scan was able to grade, quantify and localize the injury and helped in devising a
      successful management plan in 76.5% cases. CONCLUSION: Diagnostic peritoneal
      lavage is a promising bedside investigation, but is invasive with low accuracy
      for retroperitoneal injuries and high probability of nontherapeutic laparotomy
      with false positive results. The high sensitivity and accuracy rates of computed
      tomography justify its use in quantifying and estimating the grade of injury in
      order to select the appropriate management of trauma victims. Computed tomography
      is recommended as the initial investigation of choice in hemodynamically stable
      patients with blunt abdominal trauma.

PMID- 12506296
TI  - Prevalence of hepatitis C virus antibodies among different populations of
      relative and attributable risk.
AB  - OBJECTIVES: To determine the prevalence of hepatitis C virus (HCV) antibodies
      among 5 different population groups including; healthy individuals, blood donors,
      hospital health care workers, renal dialysis patients and multiple blood
      transfusion group. To compare the ratios, relative and attributable risk among
      these groups. To outline a specific policy to reduce the potential risk of HCV
      among the different groups studied. METHODS: A prospective study was carried out
      in the Department of Microbiology, Faculty of Medicine, Tripoli, Libya, over a 2
      year period for 1999 to 2001, to determine the prevalence of HCV-antibodies in
      sera collected from 5 distinct groups using enzyme-linked immunosorbent assay
      test. The groups included 800 healthy adults, 1200 individuals of blood donors,
      459 hospital health care workers, 200 patients on renal dialysis and multiple
      blood transfusion group which included 250 patients. The prevalence of HCV was
      correlated with relative and attributable risk that contributed to the
      infectivity of HCV. RESULTS: A total of 2909 individuals participated in this
      study with 1.6:1 male to female ratio. The prevalence of HCV varied from one
      group to another. It was found to be 1.6% among the general population, 1.2%
      among blood donors, 2% among hospital health care workers, 20.5% among renal
      dialysis patients and 10.8% in the multiple blood transfusion group. The relative
      risk and attributable risk among these groups varies from 1.25 to 12.8 and from
      0.4-18.9. CONCLUSIONS: This study underlines the prevalence of HCV among
      different groups. The prevalence varies from one group to another, being the
      lowest among the blood donors and general population and the highest among the
      higher risk group in particular the renal dialysis patients. Specific measures
      should be implemented to reduce such risks. These may include specific programs
      for medical education, a meticulous infection control system in the hospitals, a
      registry program and clinical follow-up for patients positive for HCV.

PMID- 12506297
TI  - Hepatocyte decay in late irradiation liver failure.
AB  - OBJECTIVE: The purpose was to examine the morbid changes of the hepatocytes in
      late irradiation liver failure. This was in an attempt to understand the reasons
      behind this failure, the extent of ultrastructural destruction, and the
      disturbance in mitotic activity of the hepatocytes. METHODS: This study was
      carried out at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia,
      from 2001-2002. Out of 80 adult albino rats of equally mixed sex, half of them
      were x-irradiated and the other half were employed as a control. At 12 and 24
      weeks after irradiation the animals were sacrificed. The liver was examined under
      both the light and the electron microscopes. The hepatocytes and their mitotic
      figures in addition to their mitochondria were counted at both occasions of rat
      sacrifice. RESULTS: The counting of these structures, as mentioned in the above
      methods, exhibited a considerable decrease in their numbers particularly when
      liver failure had prevailed. At the last sacrifice of irradiated animals, the
      liver architecture was largely preserved despite the markedly damaged
      hepatocytes, the endoplasmic reticulum seemed to have undergone detriment before
      the mitochondria. CONCLUSION: It seemed, in the light of the above results that
      impairment of the mitotic mechanism of the hepatocytes is the major factor in
      predisposition to liver failure rather than the influence imposed by the damage
      of other liver tissues apart from these cells. The study recommends re-estimation
      of irradiation dosage applied for therapeutic purposes to the liver. Further
      understanding of ultrastructural irradiation detriment may in addition to
      development in other respects of radiotherapy, help to minimize complications of
      this treatment.

PMID- 12506298
TI  - Correlation of blood volume values and pulmonary artery catheter measurements.
AB  - OBJECTIVE: To correlate the values generated by direct total blood volume
      measurement with pulmonary artery catheter parameters and commonly used
      laboratory values in the management of critically ill patients. METHODS: This
      study was carried out at the Lutheran Medical Center, Brooklyn, New York, United
      States of America, during the period 1998-1999. We prospectively correlated the
      total blood volume (TBV) values generated by the blood volume analyzer (BVA)-100
      using I131-tagged albumin, with the values obtained from pulmonary artery
      catheter (PAC) of central venous pressure, pulmonary capillary wedge pressure,
      cardiac output, and with laboratory values of hematocrit, lactate, arterial blood
      gas and mixed venous blood, in critically ill patients. Twenty-four intensive
      care unit (ICU) patients were studied. INCLUSION CRITERIA: Admission to the
      intensive care, pulmonary artery catheter insertion and (APACHE) II Acute
      Physiology and Chronic Health Evaluation score of 8-30 (mean=17.875). EXCLUSION
      CRITERIA: Pediatric patients, hemodynamically normal or stable patients,
      pregnancy, and critically ill patients that were managed in an ICU setting
      without PAC catheter. Height and weight were recorded. After the collection of an
      initial blood sample (5 cc), one cc of I131-tagged albumin (15-25 microcuries)
      was injected using a patented syringe. Five venous samples were collected after
      the isotope injection. RESULTS: The collection times were entered into the BVA
      100. Hematocrit measurements were performed in duplicate. Blood samples were
      centrifuged and one ml from the plasma of each sample was pipetted (in duplicate)
      into the sample tube then placed into the BVA-100. The results showed that the
      TBV did not correlate with either pulmonary capillary wedge pressure or central
      venous pressure, and except for the cardiac output, there is no correlation
      between pulmonary capillary wedge pressure readings or TBV results and the other
      parameters considered in this study. CONCLUSION: This method can be released from
      the research fields and can be safely incorporated into the clinical arena. It
      provides an accurate assessment of the volume status in intensive care unit
      patients.

PMID- 12506299
TI  - The efficacy of a management protocol in reducing emergency visits and
      hospitalizations in chronic asthmatics.
AB  - OBJECTIVES: To assess whether a simple protocol used in the outpatient's asthma
      clinic was effective in reducing emergency room (ER) visits and hospitalizations
      in chronic asthmatics during a year of follow-up, and to evaluate which type of
      asthmatics, according to severity of asthma, may benefit more from the protocol.
      METHODS: Prospective assessment of a simple protocol (consisted of combined
      medical and educational aspects in the form of corticosteroids inhalation as a
      monotherapy and correction of the pitfalls of inhalation technique) in reducing
      ER visits, and hospitalization in chronic asthmatics. It was performed in the
      outpatients asthma clinic at King Abdul-Aziz University Hospital, Jeddah, Kingdom
      of Saudi Arabia. A total of 128 chronic asthmatics were evaluated and followed up
      for one year between January 1999 and March 2000. RESULTS: Between January 1999
      and March 2000 the total number of ER visits, and hospitalizations in 128 chronic
      asthmatics in the year before the protocol were 269 and 85. This was reduced to
      116 ER visits and 27 hospitalizations a year after the protocol, a 55.4%, and
      68.2% reduction. While only 25% never attended ER before the protocol, almost
      58.6% did not attend ER after the protocol. The proportion that visited ER more
      frequently (at least 3 times/year) decreased from 50.8-18%, a 65% reduction.
      Similarly, patients who did not require hospitalization increased from 62.5% up
      to 85.2%. Moreover, the proportion that was hospitalized more frequently (at
      least 3 times/year) decreased from 10.2% to as low as 0.8%. Mean paired
      differences for ER visits were -1.16 1.42 with 95% confidence interval extending
      from -1.412 to - 0.916 with a P value <0.001. Mean paired differences for
      hospitalization were -0.453 0.955 with 95% confidence interval extending from 
      0.620 to -0.286 with a P value <0.001. CONCLUSION: A simple protocol in
      outpatient's asthma clinic can significantly reduce ER visits and
      hospitalizations in chronic asthmatics. All asthmatics, irrespective of severity
      benefited significantly from the protocol.

PMID- 12506300
TI  - Effect of oxygen derived free radicals and glycine on sodium-potassium adenosine
      triphosphatase in the basolateral membrane of the kidney in ischemia-reperfusion.
AB  - OBJECTIVES: The aim of the present study was to examine the effect of exposing
      rats to ischemia-reperfusion while breathing 100% oxygen or room air, to find the
      effect of glycine on renal sodium-potassium adenosine triphosphatase (Na+
      K+ATPase) and endogenous antioxidant enzymes, superoxide dismutase and catalase,
      also to ascertain the effect of ischemia-reperfusion on renal nitric oxide and
      lipid peroxides. METHODS: This study was carried out at King Saud University,
      Riyadh, Kingdom of Saudi Arabia, over a period of 11 months, February to December
      2001. All previous measurements were carried out on the renal homogenate after 60
      minutes ischemia, then after reperfusion while animals breathed room air or 100%
      oxygen and also after glycine treatment. RESULTS: The activity of Na+-K+ATPase,
      catalase and superoxide dismutase concentration was decreased significantly in
      the ischemic rats compared to the control, a further decrease was found after 20
      minutes of reflow while breathing room air. Breathing 100% oxygen resulted in a
      significant decrease in catalase and Na+-K+ATPase activity and concentration of
      superoxide dismutase, glycine caused insignificant change of these enzymes after
      ischemia-index of lipid peroxidation and nitric oxide they were significantly
      elevated following reperfusion while rats breathed room air and further elevation
      was noticed after breathing 100% oxygen. However, potassium and creatinine did
      not change in all study groups, showed significant decrease after ischemia and
      ischemia-reperfusion may be due to marked Na+ loss in urine and lack of Na+
      reabsorption. The inhibition of superoxide dismutase and catalase can be
      explained by increased reactive oxygen species during reperfusion and hyperoxia,
      also due to nitric oxide production and lipid peroxidation as shown by high
      malondialdehyde. Lack of Na+K+ATPase can be contributed to loss of antioxidant
      enzymes, nitric oxide production, and high reactive oxygen species. CONCLUSION:
      Hyperoxia in ischemia-reperfusion induces severe damage to cellular defence
      mechanisms and enhances reactive oxygen species injury. Glycine, as antioxidant,
      is involved in kidney protection from massive injury induced by ischemia
      reperfusion, protects renal antioxidant enzymes and Na+-K+ATPase, normalizes
      malondialdehyde, and nitric oxide levels. This data further supports the possible
      role of glycine therapy as an adjunct in the treatment of renal failure.

PMID- 12506301
TI  - Hematological changes in cement mill workers.
AB  - OBJECTIVES: Considering the hazards of exposure to cement dust, this study
      incorporated basic hematological parameters, erythrocyte sedimentation rate and
      the total leukocyte count. The idea was to identify a simple, readily available
      and cost effective screening test that could help in identifying the presence of
      disease, its severity, or both in cement mill workers potentially related to
      their work place. METHODS: This study was carried out in the Department of
      Physiology, Faculty of Health and Medical Sciences, Hamdard University, Karachi
      and the University of Karachi, Pakistan, during the time frame 1999-2000. In this
      study a group of 50, apparently healthy volunteers male cement mill workers were
      randomly selected with ages ranging from 20-60 years. They were matched with
      another group of 50, control healthy male subjects in terms of age, height,
      weight and socioeconomic status. Both groups met with exclusion criteria as per
      standard. The total leukocyte count was performed on an auto analyzer, (Symex-K
      1000 CP-Analyzer, Japan) and the erythrocyte sedimentation rate was measured by
      Westergren tube method. Results were compared in a mean, and on the basis of,
      period of exposure in a cement mill. RESULTS: In the present study, the mean
      values of erythrocyte sedimentation rate (p<0.05) and total leukocyte count
      (p<0.02) significantly increased, but the parameters do not revealing
      statistically significant differences between 2 groups on the basis of duration
      of exposure in a cement mill. CONCLUSION: This study has shown that exposure to
      cement dust causes increased mean values of total leukocyte count and erythrocyte
      sedimentation rate. However, this change is not related to the duration of
      exposure in a cement mill.

PMID- 12506302
TI  - Variants in origin of the left circumflex coronary artery with angiography.
AB  - OBJECTIVE: The objective of this study was to assess the anatomic variations in
      the origin of the left circumflex coronary artery in a Turkish population.
      METHOD: This study was carried out at the Sani Konukoklu Medical Center,
      Gaziantep, Turkey, during the period January 1999 through to May 2001. The
      angiographic data of 10,042 consecutive adult patients who underwent coronary
      angiography was analyzed for anomalous origin of the left circumflex coronary
      artery. RESULTS: Among 10,042 adults patients, 27 (0.3%) had anomalous origin of
      the left circumflex coronary artery. The left circumflex coronary artery arose
      from the left coronary sinus of valsalva in 15 (55.5%) patients, from the right
      coronary sinus of valsalva in 7 (25.9%) patients, and from the proximal part of
      the right coronary artery in 8 (29.6%) patients. CONCLUSION: The anomalous origin
      of the left circumflex coronary artery may not always be benign. Therefore,
      recognition of this anomaly is mandatory to prevent the risk of infarction or
      sudden death. Special surgical considerations must be made when performing
      valvular replacement in patients with anomalous left circumflex coronary artery.

PMID- 12506303
TI  - Rebound hyperbilirubinemia in term infants after phototherapy.
AB  - OBJECTIVE: To determine whether a rebound in serum bilirubin level occurs within
      24 hours after discontinuation of phototherapy in term infants with
      hyperbilirubinemia. METHODS: A retrospective medical record review of term
      infants with hyperbilirubinemia requiring phototherapy who were admitted over 24
      months, June 1999 to December 2001, at King Abdul-Aziz University Hospital,
      Jeddah, Kingdom of Saudi Arabia was completed. Total serum bilirubin levels (TSB)
      at and up to 24 hours after termination of phototherapy (follow-up levels) were
      recorded. The difference between mean TSB level at termination of phototherapy
      and at follow-up was calculated using the paired t test. RESULTS: Three hundred
      and one infants, 53% (n=161) were boys, mean standard deviation (SD) for
      gestational age was 39.4 +/- 1.4 weeks, mean birth weight was 3200 +/- 600 g,
      mean TSB SD at termination of phototherapy was 193 +/- 46 micromole/liter
      (micromol/l) and at follow-up was 188 +/- 45 micromol/l for all infants with
      either positive or negative direct coombs' test results. The difference in mean
      TSB level at discontinuation of phototherapy and at follow-up was statistically
      significant, (t=3.12, P=0.002). The mean TSB level at termination of phototherapy
      was 179 +/- 47 micromol/l and at follow-up was 177 +/- 47 micromol/l for 65
      infants with positive direct coombs' test results. This difference was
      statistically insignificant (t=0.725, P=0.47). The mean time interval between the
      termination of phototherapy and the measurement of follow-up TSB level was 8.3 +/
      5.3 hour. CONCLUSION: The rebound of bilirubin level after termination of
      phototherapy in otherwise healthy term infants is minimal; thus measurement of
      serum bilirubin is not required after termination of phototherapy and adds
      unnecessary expense, prolongs hospitalization, or both.

PMID- 12506304
TI  - Coasting. A viable option for patients at risk of ovarian hyperstimulation
      syndrome.
AB  - OBJECTIVES: To present our experience in 48 coasted patients and how they
      performed in terms of the number of eggs collected, numbers of embryos available
      for embryo transfer after in vitro fertilization, pregnant and on going pregnancy
      rate. METHODS: The study was conducted at Lister Hospital, London, United
      Kingdom, during the period October 1998 through to May 2001. For the purpose of
      the study, we selected coasted cycles in patients who were less than 38 years of
      age (n=48 patients). A control group of cycles consisted of all cycles during the
      same period in patients less than 38 years of age, who were not coasted because
      they did not fulfil the at risk criteria, but yet we collected 20 oocytes or more
      (n=115 cycles, 113 patients). RESULTS: The study showed that there is no
      significant difference in outcome between the 2 groups (52.1% pregnancy rate in
      the coasted group versus 51.3% in the control group). The incidence of severe
      ovarian hyperstimulation syndrome was 4.3% in the study group versus 12.2% in the
      control but this did not reach statistical difference. CONCLUSION: We therefore
      conclude that coasting is a safe and viable option for patients at risk of
      ovarian hyperstimulation syndrome in an assisted conception cycle that allows the
      transfer of fresh embryos.

PMID- 12506305
TI  - Uterine didelphus with obstructed hemivagina.
AB  - Complex congenital anomalies of the mullerian ducts can occur in isolation or in
      association with other developmental disorders. They result from non-development
      or non-fusion of the mullerian ducts or the failure of reabsorption of the
      uterine septum. Early diagnosis is necessary to relieve symptoms, optimize
      preservation of the genital organs and prevent the development of endometriosis.
      We present a case report to highlight this phenomenon.

PMID- 12506306
TI  - Obstetric performance of a patient with multiple uterine and cervical fibroids
      and expectant management of retained placenta.
AB  - The aim of this case report is to describe the obstetric performance of a patient
      with multiple uterine and supravaginal cervical fibroids. A 36-year-old, gravida
      3 para 0+2 with multiple uterine and cervical fibroids presented with inevitable
      abortion at 17 weeks gestation. She had a spontaneous rupture of membranes
      followed by expulsion of fetus as breech with entrapment of aftercoming head by a
      cervical fibroid. Oxytocin infusion and digital traction were able to deliver the
      fetus. The placenta, however, was trapped in the fundal area and could not be
      delivered under general anesthesia because of mechanical obstruction by the
      fibroid. Expectant management was successful in expulsion of the placenta within
      7 days without complication.

PMID- 12506307
TI  - Acquired reactive perforating collagenosis associated with sick euthyroid
      syndrome.
AB  - Acquired reactive perforating collagenosis is a rare skin disorder associated
      with several systemic diseases, particularly diabetes and chronic renal failure.
      A 52-year-old Saudi female patient with a known case of diabetes mellitus type
      II, chronic renal impairment, hypertension, peripheral vascular disease,
      congestive heart failure, stroke and left hemiplegia presented with multiple
      pruritic skin eruption on the trunk and extremities. We believe that this is the
      first case of acquired reactive perforating collagenosis in association with sick
      euthyroid syndrome to be reported.

PMID- 12506308
TI  - Are we underestimating the leukemogenic risk of hydroxyurea.
AB  - Hydroxyurea is an established drug that has been used for the treatment of
      myeloproliferative disorders and some solid tumors for some time. In recent years
      it has also been found to be effective in the treatment of sickle cell disease.
      Short term side effects are not serious, and are manageable. The major concern is
      the potential leukemogenesis with long term use. The risk of leukemogenesis is
      not defined with its use in benign hematological conditions. We report a case of
      acute myeloid leukemia with no preceding myelodysplastic syndrome, occurring
      after 2 years of hydroxyurea therapy in a patient with sickle cell disease.

PMID- 12506309
TI  - Treatment of tuberculous spondylitis at the cervicothoracic junction. Clinical
      impact of surgery by means of a sternotomy.
AB  - The operative treatment of tuberculous spondylitis remains a challenge with
      regard to the surgical approach to the cervicothoracic junction. In addition, it
      is difficult to restore the resected vertebral bodies. Two cases of tuberculous
      spondylitis in this area are presented. The first case concerns a 25-year-old
      African patient suffering from the effects of tuberculous spondylitis:
      Destruction of vertebral bodies dorsal (D)1, D2, and D3, kyphosis coupled with
      compression of the spinal cord, as well as incomplete motor and sensory
      paraplegia (Frankel grade C). The operative treatment of tuberculous spondylitis
      that is described, approached the cervicothoracic junction by means of a
      sternotomia. Corpectomy of vertebral bodies D1 through D3 were followed by their
      restoration with the help of a titanium cage. As a result, the paraplegia
      disappeared. Ventral decompression was followed by dorsal instrumentation. The
      results of the operation are decompression of the spinal cord, correction of the
      kyphosis, and stable fusion followed by restitution of the paraplegia. Primary
      stability was provided by the use of a titanium cage and dorsal instrumentation.
      There was no need for an external brace. There was no loss of correction 3 years
      after the operation. The 2nd case concerns a 49-year-old European patient
      suffering from thoracic pain radiating around the chest. A partial destruction of
      D2 and D3 with kyphosis and compression of the spinal cord because of a
      tuberculous spondylitis were detected, neurological deficits were not found. The
      corpectomy of D2 and D3 were proceeded by means of a sternotomy, the defect was
      restored with the help of a titanium cage. Due to the use of a ventral Morscher
      plate an additional dorsal instrumentation was not necessary. The patient was
      fixed in a minerva plaster for 3 months. There was no loss of correction 2 years
      after the operation. Both patients are manual workers and postoperatively adapted
      to their former work.

PMID- 12506311
TI  - Prevalence and clinical usefulness of thyroid antibodies in different diseases of
      thyroid.

PMID- 12506310
TI  - Impact of Ramadan fasting on birth weight in 4 hospitals in Sana'a city, Yemen.

PMID- 12506312
TI  - Globalization and health: challenges imposed upon the medical profession.

PMID- 12506313
TI  - Surgery and postoperative mebendazole in the treatment of hydatid disease.

PMID- 12506314
TI  - Glycemic index of 3 varieties of dates.

PMID- 12506315
TI  - An overview of vagal airway receptors.
AB  - Breathing is critically depending on a variety of sensory feedbacks from multiple
      sources for its optimal performance. The sensory information from the lung and
      airways probably provides one of the most important feedbacks to adjust the
      respiratory controller to generate optimal breathing movements. Since Breuer and
      Hering made the seminal report regarding role of the vagus nerve in control of
      breathing in 1868, airway sensory receptors have been a subject for intensive and
      extensive studies. After more than a century investigation, our knowledge
      accumulates immensely, however, our understanding of the nature of these sensory
      receptors is still far from complete. This brief review provides an overview on
      this topic.

PMID- 12506316
TI  - Microinjection of adrenomedullin into rostral ventrolateral medulla increases
      blood pressure, heart rate and renal sympathetic nerve activity in rats.
AB  - The present study was undertaken to examine the effects of microinjection of
      adrenomedullin (AM) into rostral ventrolateral medulla (RVLM) on mean arterial
      pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in 34
      anesthetized Sprague-Dawley rats. The results obtained are as follows. (1)
      Following microinjection of AM (10 micromol/L, 200 nl) into the RVLM, MAP, HR and
      RSNA were significantly increased from 99.09+/-3.32 mmHg, 370.78+/-7.84 bpm and
      100+/-0% to 113.57+/-3.64 mmHg (P>0.001), 383.28+/-7.38 bpm (P>0.001) and
      123.72+/-2.74% (P>0.001), respectively. (2) Pretreatment with microinjection of
      calcitonin gene-related peptide receptor antagonist CGRP8-37 (100 micromol/L, 200
      nl) did not change the effects of AM. (3) L-arginine (100 mg/kg, 0.2 ml, i.v.),
      an NO precursor, abolished the effects of AM. This study demonstrates that AM
      acting at the rostral ventrolateral medulla may produce significant
      cardiovascular responses, the effects are not mediated by CGRP receptor but may
      be abolished by NO.

PMID- 12506317
TI  - Effect of agmatine on intracellular free calcium concentration in isolated rat
      ventricular myocytes.
AB  - The present study was to investigate the effects of agmatine (Agm) on free
      intracellular calcium concentration ([Ca(2+)]( i )) of isolated rat ventricular
      myocytes. [Ca(2+)]( i ) was measured by confocal microscopy in single rat
      ventricular myocytes which were dissociated by enzymatic dissociation method and
      loaded with Fluo 3-AM. The changes in [Ca(2+)]( i ) were represented by
      fluorescence intensity (FI) or relative fluorescence intensity (F/F(0)%). The
      results showed that the control level of FI value of single rat ventricular
      myocytes was 128.8+/-13.8 and 119.6+/-13.6 in the presence of normal Tyrode's
      solution containing Ca(2+) 1.0 mmol/L and Ca(2+)-free Tyrode's solution,
      respectively. There was no difference between these two groups (P>0.05). Agm 0.1,
      1, and 10 mmol/L significantly reduced the [Ca(2+)]( i ) in both extracellular
      solutions in a concentration-dependent manner. The similar effect of Agm on
      [Ca(2+)]( i ) was also observed in the presence of EGTA 3 mmol/L. KCl 60 mmol/L,
      PE 30 micromol/L, and Bay-K-8644 10 micromol/L, all these substances induced
      [Ca(2+)]( i ) elevations in ventricular myocytes. Agm (0.1, 1, and 10 mmol/L)
      markedly inhibited the increase in [Ca(2+)]( i ) induced by KCl, phenylephrine
      (PE), and Bay-K-8644. When Ca(2+) waves were produced by increasing extracellular
      Ca(2+) concentration from 1 to 10 mmol/L, 1 mmol/L Agm could block the
      propagating waves of elevated [Ca(2+)]( i ), and reduce the velocity and duration
      of propagating waves. These results suggest that Agm possesses an inhibitory
      effects on [Ca(2+)]( i ) via blocking voltage-dependent Ca(2+) channel, and
      possibly by alleviating calcium release from SR in single isolated rat
      ventricular myocytes.

PMID- 12506318
TI  - [Colocalization of 11beta-hydroxysteroid dehydrogenase type I and glucocorticoid
      receptor and its significance in rat hippocampus].
AB  - This paper was designed to observe the colocalization of 11beta-HSD1 and GR, and
      its significance in the rat hippocampus. Immunocytochemical dual-staining showed
      that not only 11beta-HSD1 but also GR immunoreactive substances were present in
      the cultured rat hippocampal neurons. Moreover, they were colocalized in the same
      hippocampal neuron. Synthetic glucocorticoid dexamethasone (DEX) up-regulated the
      protein expression and activity of 11beta-HSD1 in the cultured hippocampal
      neurons, as determined by Western blot and thin layer chromatography (TLC)
      respectively. The transfection of PC12 cells with the plasmid containing promoter
      sequence of 11beta-HSD1 gene and the reporter gene of CAT enzyme was conducted.
      DEX up-regulated the reporter gene expression in the system described above. The
      up-regulation of 11beta-HSD1 and reporter gene expression induced by DEX were
      both blocked by GR antagonist RU38486. Our study suggests that the colocalization
      of 11beta-HSD1 and GR in the hippocampus may be implicated in the up-regulation
      of 11beta-HSD1 expression by glucocorticoids combining to its promoter region,
      which in turn produces more biologically active glucocorticoids necessary for the
      binding of low affinity of GR.

PMID- 12506319
TI  - Inhibitory effect of adrenomedullin on L-type calcium currents in guinea-pig
      ventricular myocytes.
AB  - The effects of adrenomedullin (ADM) on the L-type calcium currents (I(Ca,L)) and
      the mechanism of the signal transduction process were studied. Enzymatically
      isolated guinea-pig ventricular myocytes were used to measure ICa,L with whole
      cell patch-clamp techniques. ADM at the concentrations of 1-100 nmol/L decreased
      ICa,L in a dose-dependent manner (P<0.05). ADM22-52) (100 nmol/L), a specific ADM
      receptor antagonist, completely abolished the ADM-induced inhibition of ICa,L.
      Pretreatment of the cells with H-89 (10 micromol/L), a specific PKA inhibitor,
      did not attenuate the effects of ADM. Intracellular application of 10 micromol/L
      PKC19-36), a specific PKC inhibitor, prevented the ADM-induced inhibition of the
      ICa,L, while the specific PKC activator PMA could mimic the effects of ADM on the
      ICa,L. PMA (1 micromol/L) decreased the ICa,L by 32.26+/-4.20%(P<0.05). These
      findings indicate that ADM can inhibit the ICa,L in guinea-pig ventricular
      myocytes, and the inhibition is mediated by the specific ADM-receptor and an
      activation of protein kinase C.

PMID- 12506320
TI  - [Effects of ATP concentration and hypoxic exposure on RNA and protein synthesis
      activity in isolated mitochondria from rat brain].
AB  - To explore the effects of ATP concentration in the medium and hypoxia exposure on
      mitochondrial DNA expression at transcriptional and translational level, rats
      were exposed to hypoxia in a hypobaric chamber simulating 4000 m above sea level
      for 3 d (acute hypoxia) or 40 d (chronic hypoxia). Cerebral cortex mitochondria
      were isolated from control and hypoxia-exposed rats by centrifugation program.
      The activities of intramitochondrial RNA and protein synthesis were measured
      respectively by the methods of incorporation of (3)H-UTP or (3)H-Leucine in a
      cell-free system in vitro in isolated organelle. The effect of different ATP
      concentrations in medium on incorporation activity of mitochondria from control
      rat brains was observed. The results showed that there was a 40% reduction in RNA
      synthesis and a 60% inhibition in protein synthesis in isolated mitochondria in
      vitro in acute hypoxia exposure compared to control. But in chronic hypoxic
      exposure, the inhibition of both RNA synthesis and protein synthesis was
      alleviated, being 72% and 76% of the normoxic control, respectively. Furthermore,
      the effect of ATP concentration in medium on mitochondrial RNA and protein
      synthesis in vitro showed two phases. The mitochondrial RNA and protein synthesis
      were inhibited when ATP concentration was either above or below 1 mmol/L in the
      incubation medium. These results indicate that hypoxia exposure affects the
      expression of mtDNA at both transcription and translation levels. It also
      suggests that the improvement of mitochondrial semi-automation during chronic
      hypoxic exposure may be at least one of the cellular mechanisms of body
      adaptation to hypoxia. The regulation of ATP in mitochondrial RNA and protein
      synthesis is therefore an economic and effective mode of regulation.

PMID- 12506321
TI  - [Effect of intracerebroventricular injection of histamine on carotid sinus
      baroreceptor reflex in anesthetized rats and its mechanism].
AB  - The changes in carotid sinus baroreceptor reflex (CSR) performance induced by
      intracerebroventricular injection (i.c.v.) of histamine (HA) were investigated.
      The effects of pretreatment with HA receptors antagonists into the
      cerebroventricle or nucleus of solitary tract (NTS) on the responses of CSR to HA
      were also examined. Intracarotid sinus pressure (ISP)-mean arterial pressure
      (MAP) relationship curve was constructed by fitting to the logistic function with
      five parameters in 50 Wistar rats anesthetized with pentobarbital sodium. The
      left and right carotid sinus regions were isolated from the systemic circulation
      and the ISP was altered in a stepwise manner. The main results obtained are as
      follows. (1) i.c.v. injection of HA (100 ng) significantly shifted the ISP-MAP
      relationship curve upwards and moved the middle part of ISP-Gain relationship
      curve downwards, and reduced the MAP range and maximum gain (G(max)), but
      increased the threshold pressure (TP), saturation pressure (SP) and ISP at G(max)
      (ISP (Gmax)). (2) The pretreatment with H(1) or H(2) receptors antagonist,
      chlorpheniramine (CHL, 5 microg) or cimetidine (CIM, 15 microg), could obviously
      diminish the above-mentioned changes in CSR performance induced by HA, but the
      effect of CIM was less remarkable than that of CHL. (3) The pretreatment with
      both CHL and CIM (5 microg and 15 microg) at the same time abolished the
      responses of CSR performance to HA completely. (4) After microinjection of CHL
      (0.5 microg) or CIM (1.5 microg) into the NTS, the responses of CSR to HA were
      similar to those after i.c.v. CHL or CIM, but the change in TP was significantly
      decreased. These findings suggest that the intracerebroventricular administration
      of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity.
      The response of CSR to HA might be mediated by both central H(1) and H(2)
      receptors, especially by H(1) receptors. The effects of the central HA on CSR
      might be related to a histaminergic descending pathway from the hypothalamus to
      NTS. It is suggested that the HA receptors in the NTS play an important role in
      the responses of CSR to HA.

PMID- 12506322
TI  - [Difference in action sites between mecamylamine and hexamethonium on nicotinic
      receptors of sympathetic neurons].
AB  - To compare the difference in action sites between mecamylamine (MEC) and
      hexamethonium (HEX) on nicotinic receptors of sympathetic neurons, we
      investigated the effects of MEC and HEX on the nicotine-induced currents in
      cultured superior cervical ganglion neurons by whole-cell patch clamp technique.
      The IC(50) of MEC and HEX for antagonizing the effect of 0.08 mmol/L nicotine was
      0.0012 and 0.0095 mmol/L, respectively. Both MEC and HEX accelerated the
      desensitization of nicotinic receptors. Furthermore, by comparing their effects
      at holding potentials 30, 70 and 110 mV, it was indicated that their suppressing
      effect on the nicotine-induced currents was voltage-dependent. However, different
      from that of HEX, the inhibitory effect of MEC increased with administering the
      mixture of MEC and nicotine at intervals of 3 min, indicating a use-dependent
      effect of MEC. It is concluded that the action site of MEC on nicotinic receptors
      of sympathetic neurons is different from that of HEX.

PMID- 12506323
TI  - [Changes in mechano-receptive properties of Abeta-fiber induced by antidromical
      electrical stimulation of the cutaneous nerve from adjacent spinal segment].
AB  - The purpose of the present study was to observe whether primary afferent Abeta
      fiber is involved in the information transmission between peripheral terminals of
      adjacent dermatomes. The dorsal cutaneous nerve branches of spinal nerves from
      T(8) to T(12) segments were cut proximally. One peripheral stump end of the cut
      nerves was dissected into a few filaments for the examination of mechanoreceptive
      properties of single Abeta-fibers and their discharges were observed while the
      other end was stimulated antidromically. Fifty Abeta-units were recorded in forty
      two intact rats. After an electrical stimulation (0.45 mA, 0.1 ms, 20 Hz, for 10
      s) was delivered to the stimulated nerve, the size of the receptive field of
      60.6% (n=33) Abeta-fibers extended. The mean area of receptive fields of all
      examined units enlarged from 8.94+/-6.51 mm(2) to 20.34+/-16.17 mm(2) (P<0.01)
      and the shapes of the receptive fields of 81.8% (n=20) units changed from a dot,
      round or ellipse with its long axis in parallel with the longitudinal axis of the
      body to an oblique ellipse with the longitudinal axis of the body. The
      mechanoreceptive threshold of 68.0% (n=50) units decreased with a reduction in
      mean threshold from 2.37+/-1.24 to 2.29+/-1.24 mN (P<0.05). The duration of these
      changes in mechano-receptive properties increased from 52.23+/-9.27 to 56.93+/
      15.76 min. Meanwhile, increasing discharge was found in 50.0% (n=50) units but
      lasted only for 1.52+/-0.46 min. The changes in mechanoreceptive properties
      appeared simultaneously with discharge changes but had longer duration than that
      of discharge change (P<0.01). Discharges changes usually appeared in those units
      with the changes in mechanoreceptive properties following an antidromical
      electrical stimulation of adjacent spinal segment. These results suggest that low
      threshold mechanoreceptive Abeta-fibers are affected by antidromical electrical
      stimulation of the cutaneous nerve from an adjacent spinal segment, indicating
      that information transmission occurs between the two endings of peripheral
      afferent nerves from adjacent spinal segments without any involvement of the
      central nervous system, and that Abeta-fibers are involved in the process of
      information transmission between peripheral terminals from adjacent spinal
      segments.

PMID- 12506324
TI  - [CoCl2-induced enhancement of glucose transport activity in mediating hypoxic
      tolerance in cultured hippocampal neurons].
AB  - The effect of CoCl(2) pretreatment on glucose transport activity of cultured
      newborn rat hippocampal neurons and its role in neuronal hypoxic tolerance were
      observed. The results showed that the 2-deoxy-D-[1-(3)H ]glucose uptake rate and
      the mRNA expressions of glucose transporters (GLUT1 and GLUT3) in the hippocampal
      neurons were significantly increased after a 24-hour pretreatment with CoCl(2).
      The cell injury induced by 6-hour or 8-hour hypoxic exposure was also greatly
      reduced by CoCl(2) pretreatment. The protective effect of CoCl(2) on the neurons
      was largely abolished by cytochalasin B, a specific inhibitor of glucose
      transporters. The results suggest that CoCl(2) can increase mRNA expressions of
      GLUT1 and GLUT3 and glucose transporter activity of the neurons, which may be an
      important mechanism for the increased tolerance of the neurons to hypoxia.

PMID- 12506325
TI  - [The correlations between plasma TNF-alpha, NO, NOS levels and brain
      lateralization in mice].
AB  - The brain modulates the immune system in an asymmetrical way, as shown by the
      association between paw preference and immune response in the mice. The purpose
      of the present work was to study the relationship between plasma tumor necrosis
      factor-alpha (TNF-alpha), nitric oxide (NO) and nitric oxide synthase (NOS) and
      brain lateralization. In the study, paw preference test was used to select right
      pawed, left-pawed and ambidextrous mice. Mice were classified as the right-pawed
      if the right paw entry (RPE) score was equal to or greater than 30 (30-50), as
      the left-pawed if the score was equal to or less than 20 (0-20), and as the
      ambidextrous if the score was between 21 and 29. One week after the paw
      preference testing, the animals were injected intraperitoneally with either
      sterilized 0.9% saline or lipopolysaccharide (LPS) (5 microg/0.5 ml NS) and were
      killed 2 h later. Plasma was collected from each mouse. The level of plasma TNF
      alpha was measured with ELISA kits provided by ENDOGEN. NO and NOS levels of
      plasma were detected with kits from Juli Biotechnology Company. The results
      showed that (1) in the normal mice, ambidextrous mice had higher NO levels
      compared with left-pawed mice (P<0.05). After the injection of LPS, plasma level
      of TNF-alpha was lower in left-pawed mice compared with those of the right-pawed
      and ambidextrous mice; plasma level of NO was higher in ambidextrous mice
      compared with those of the right- (P<0.01) and left-pawed (P<0.05) ones, and
      there was no significant difference in the plasma levels of NOS among
      ambidextrous, right- and left-pawed mice. (2) Immune parameters were correlated
      with the RPE scores. The shape of the curve describing this relation was similar
      to a parabola. In general, the levels of TNF-alpha, NO, NOS rose along with the
      increase of RPE if the scores were in the score range of left-pawed mice.After
      that, they reached a peak if the scores were in the score range of ambidextrous
      mice. Then they declined along with the increase of RPE if the scores were in the
      score range of right-pawed mice. In conclusion, plasma levels of TNF-alpha, NO
      and NOS were associated with brain lateralization, suggesting that the activities
      of Mo/Mphi were influenced by brain lateralization, and that the immune
      parameters were correlated with the RPE scores.

PMID- 12506326
TI  - [Effects of hypoxic exposure on coordinative expression of cytochrome oxidase
      subunits I and IV in rat cerebral cortex].
AB  - This study was intended to evaluate the effects of hypoxic exposure on gene
      expression and coordination of cytochrome oxidase (COX) subunits I (COX I) and IV
      (COX IV) encoded by mtDNA and nDNA respectively in rat cerebral cortex. Male
      Wistar rats were exposed to hypoxia in a hypobaric chamber simulating high
      altitude at 5000 m for 2, 5, 15 and 30 d. Control rats were fed outside the
      hypobaric chamber (the height was 300 m above sea level). Rats were sacrificed
      and mitochondria from cerebral cortex were isolated by differential
      centrifugation at each time point. COX I and COX IV proteins in isolated rat
      cerebral cortex mitochondria were detected by Western blot analysis and mRNA in
      the cerebral cortex by RT-PCR. The ratios of protein and mRNA were used to
      estimate the coordinative expression of two subunits. The results showed that COX
      I mRNA increased significantly at 2 and 5 d, and decreased to the control level
      at 15 and 30 d; COX IV mRNA remarkably increased at 2, 5 and 15 d, and dropped
      below the control level at 30 d. The mRNA ratio of COX IV to COX I reached a peak
      at 15 d, but showed no differences between other time points. The Western blot
      analysis of COX I and COX IV in isolated rat cerebral cortex mitochondria showed
      no obvious changes during hypoxic exposure. Our findings demonstrate that hypoxia
      can affect mRNA expression of COX I and COX IV and their coordination, while
      protein expression of both subunits are stable and coordinative. This study
      suggests that the expression of COX I and COX IV proteins during hypoxic exposure
      is coordinately regulated by post-transcriptional mechanisms.

PMID- 12506327
TI  - [Changes in potassium currents of vascular smooth muscle cells isolated from
      hindquarter arteries of rats after 4 weeks simulated weightlessness].
AB  - The changes in potassium currents of vascular smooth muscle cells (VSMCs)
      isolated from saphenous arteries and the 2nd-6th order branches of the mesenteric
      arteries of 4-week tail-suspended rats (SUS) were examined using whole cell patch
      clamp technique. The resting potential (RP) of the VSMCs from SUS group was more
      negative compared with that of the control group (CON).The whole cell potassium
      current densities of VSMCs isolated from the saphenous arteries and small
      mesenteric arteries in SUS group were significantly larger than those of the CON
      group.The BK(Ca) and K(V) current densities of VSMCs from saphenous arteries and
      small mesenteric arteries from SUS group were also significantly larger than
      those from the CON group.It is speculated that the hyperpolarization of VSMCs and
      decreased calcium influx through voltage-dependent calcium channels might be one
      of the electrophysiological mechanisms involved in the depressed vasoreactivity
      of hindquarter arteries induced by simulated weightlessness.

PMID- 12506328
TI  - [Effect of a proteinase-activated receptor-2 (PAR-2) agonist on tryptase release
      from human mast cells].
AB  - Proteinase-activated receptor-2 (PAR-2) expression has been observed on numerous
      cell types. However, little is known about the functional expression of PAR-2 in
      human mast cells. In the current study, the actions of a PAR-2 agonist trans
      cinnamoyl-Leu-Ile-Gly-Arg-Leu-Orn-amide (tc-LIGRLO) on tryptase release from
      dispersed human colonic mast cells were examined. The results showed that tc
      LIGRLO was able to induce a fold increase in tryptase release over the basal
      level following a 15 min incubation of colonic mast cells, whereas tc-OLRGIL did
      not have any effect on tryptase release. The potency of tc-LIGRLO appeared
      greater than that of anti-IgE and calcium ionophore A23187 (CI) in induction of
      tryptase release. Extending the incubation time to 30 min had no significant
      effect on the actions of tc-LIGRLO or anti-IgE. In the time course study, it was
      observed that the tryptase release from mast cells induced by tc-LIGRLO started
      at 1 min and peaked at 3 min following incubation. The above-mentioned results
      indicate that tc-LIGRLO is a potent stimulus of tryptase release from human mast
      cells, which strongly suggests that PAR-2s are expressed in human mast cells.

PMID- 12506329
TI  - [Periodic changes in serum testosterone levels after ejaculation in men].
AB  - The purpose of this study was to determine the changes in sex hormone level in
      men after ejaculation. The serum testosterone concentrations of 28 male
      volunteers were investigated daily during abstinence period after ejaculation. We
      found that fluctuations of testosterone levels from day 2 to day 5 of abstinence
      were minimal. On day 7 of abstinence, a peak of serum testosterone appeared,
      reaching 145.7% of the baseline (P<0.01). After the peak, no regular fluctuation
      was observed. Ejaculation was the premise and beginning of the 7 days' periodic
      phenomenon. If there was no ejaculation, there was no periodical changes in serum
      testosterone level. These results indicate that the periodic change in serum
      testosterone level is caused by ejaculation.

PMID- 12506330
TI  - [Inhibition of sodium currents in acutely isolated hippocampal CA1 neurons of
      rats by magnesium sulfate].
AB  - The effects of magnesium sulfate (MgSO4) on sodium currents (Na(+) currents) were
      studied in freshly dissociated hippocampal CA(1) neurons of rat using the whole
      cell patch-clamp technique. The results indicated that MgSO4 caused a
      concentration-dependent and voltage-dependent decrease in Na(+) currents. The
      half-inhibitory concentration (IC(50)) was 4.05 mmol/L. This action was frequency
      independent. The results also showed that 4 mmol/L MgSO4 shifted the steady state
      activation curve of Na(+) currents towards positive potential (control V(h)=
      55.8+/-6.8 mV, MgSO4 V(h)=-34.2+/-6.2 mV, n=8, P<0.01) without changing the slope
      factor. However, the steady state inactivation curve was not affected. These
      results suggest that blockade of Na(+) currents by MgSO4 might be an
      interpretation for its neuroprotection against damages induced by ischemia and
      oxygen deprivation.

PMID- 12506331
TI  - Non-alcoholic fatty liver disease: treatment options based on pathogenic
      considerations.
AB  - NASH is a frequent liver disease that develops in close association with IR and
      may progress to cirrhosis. Exclusion of excessive alcohol consumption as well as
      of other liver diseases and liver histology are required for diagnosis. Progress
      in the understanding of the pathophysiology of NASH allows interesting
      therapeutic considerations. It is logical to treat the associated metabolic
      conditions to influence the disease activity and progression. In view of
      promising preliminary data, several drugs are currently used in clinical trials.

PMID- 12506332
TI  - Appropriateness of digoxin level monitoring.
AB  - AIM: To evaluate the proportion of inappropriate digoxin level determinations.
      METHODS: We performed a retrospective analysis of 210 randomly selected digoxin
      plasma level determinations in inpatients. Appropriateness criteria were defined
      combining existing criteria from the literature. The main outcome measure was the
      proportion of digoxin levels assessed as inappropriate using a priori defined
      criteria. RESULTS: Of the 210 digoxin levels assessed, 125 (59%; 95% confidence
      interval [CI] 52-66%) were considered inappropriate, 81 (39%; 95% CI: 32-45%)
      were appropriate, and 4 (2%) determinations could not be evaluated. Of the 125
      levels assessed as inappropriate, the majority (79%) was performed as routine
      monitoring. Extrapolating the results to all digoxin level determinations in
      inpatients at our institution resulted in estimated yearly costs of CHF 28,025
      (approximately B 18,995) for inappropriate digoxin level determinations.
      CONCLUSIONS: The majority of digoxin plasma levels determinations were assessed
      as inappropriate. This was mainly due to the lack of an adequate indication and
      due to incorrect timing of drawing the blood samples. With regard to indication,
      routine monitoring was the reason for the majority of levels assessed as
      inappropriate.

PMID- 12506333
TI  - An evaluation of thromboembolism prophylaxis in acutely ill medical patients.
AB  - AIM OF THE STUDY: To examine the frequency and adequacy of thromboprophylaxis in
      acutely ill medical patients hospitalised in a primary-tertiary care hospital.
      METHODS: We carried out a cross-sectional study of 266 patients hospitalised in
      the three medical services of the University Hospital of Geneva. After exclusion
      of patients (64) treated by therapeutic anticoagulation, 202 patients were
      included. The appropriateness of thromboprophylaxis was assessed by means of
      explicit criteria developed by the Hopital Lariboisiere, Paris, France. RESULTS:
      Overall, 87 patients (43.1%) received thromboprophylaxis. With explicit criteria,
      this percentage decreased to 37.6% (p = 0.25). According to the explicit criteria
      used, about half of the patients were unnecessarily treated, whereas 42% of the
      patients who should have been treated were not. Agreement between implicit
      criteria (or observed treatment rate) and explicit criteria assessed by kappa
      coefficient is 0.2. Two services (A, B) had an overuse of thromboprophylaxis (p =
      0.002) and service C tended to under-use thromboprophylaxis (p = 0.45).
      CONCLUSION: Even though the appropriateness of the applied explicit criteria has
      not been thoroughly validated, these results suggest that implicit criteria are
      associated with considerable uncertainty leading to both over or under-use of
      thromboprophylaxis. Further research is needed to better understand
      thromboembolic risk factors in acutely ill medical patients and to elaborate
      explicit evidence-based criteria for thromboprophylaxis in this setting.

PMID- 12506334
TI  - Outcome of treatment of pulmonary tuberculosis in Switzerland in 1996.
AB  - PRINCIPLES: Adequate treatment of pulmonary tuberculosis cures patients and
      reduces transmission. The study assesses treatment outcomes under current
      conditions in Switzerland. METHODS: Retrospective cohort study including all TB
      cases with positive sputum cultures notified to the national surveillance system
      between July 1996 and June 1997. Ten months after notification, treating
      physicians reported the outcomes using WHO categories. RESULTS: Of 265 patients,
      209 (79%) completed at least 6 months' treatment, 3 (1%) were treatment failures,
      23 (9%) died, 8 (3%) defaulted from treatment and 22 (8%) left the country. The
      proportion of successful treatments did not significantly differ between the 103
      Swiss-born (80%) and the 162 foreign-born (78%) patients. There were 19 deaths
      (18%) in the Swiss-born and 4 (2%) in the foreign-born groups; death was caused
      by TB in two patients, 10 died of other causes (cause unknown in 11). In the
      foreign-born group there were 31 (19%) potentially unsatisfactory outcomes
      (treatment failure, default from treatment, transfer abroad) and in the Swiss
      born group 2 (2%). Default from treatment involved 8 patients, 6 of whom were
      asylum seekers. In a multivariate analysis potentially unsatisfactory outcomes
      were not significantly associated with foreign origin but with status as a
      foreigner of irregular or unknown legal status (adj. OR 8.8; 95% CI 1.4 to 53.7).
      CONCLUSIONS: Overall treatment success rates are satisfactory and similar to
      those of other western European countries. Potentially unsatisfactory outcomes
      are more common in foreign-born persons of irregular legal status. Tracking of
      non-adherent patients by health workers could further improve outcomes.

PMID- 12506335
TI  - Excessive use of zopiclone: a case report.

PMID- 12506336
TI  - CD36 polymorphism is associated with protection from cerebral malaria.
AB  - The human protein CD36 is a major receptor for Plasmodium falciparum-infected
      erythrocytes and contributes to the pathology of P. falciparum malaria. We
      performed variation screening of the CD36 gene and examined the possible
      association between CD36 polymorphisms and the severity of malaria in 475 adult
      Thai patients with P. falciparum malaria. Accordingly, we identified nine CD36
      polymorphisms with a high-frequency (>15%) minor allele. Of these, the
      frequencies of the -14T-->C allele in the upstream promoter region and the -53G-
      >T allele in the downstream promoter region were significantly decreased in
      patients with cerebral malaria compared to those with mild malaria (P=.016 for 
      14T-->C and P=.050 for -53G-->T). The analysis of linkage disequilibrium (LD)
      between the nine common polymorphisms revealed that there are two blocks with
      strong LD in the CD36 gene and that the -14T-->C and -53G-->T polymorphisms are
      within the upstream block of 35 kb from the upstream promoter to exon 8. Further
      association testing after the second variation screening in the upstream block
      indicated that the in3(TG)(12) (i.e., 12 TG repeats in intron 3) allele is most
      strongly associated with the reduction in the risk of cerebral malaria (odds
      ratio 0.59; 95% confidence interval 0.40-0.87; P=.0069). We found, by reverse
      transcriptase PCR amplification, that in3(TG)(12) is involved in the
      nonproduction of the variant CD36 transcript that lacks exons 4 and 5. Since exon
      5 of the gene is known to encode the ligand-binding domain for P. falciparum
      infected erythrocytes, in3(TG)(12) itself or a primary variant on the haplotype
      with in3(TG)(12) may be responsible for protection from cerebral malaria in
      Thailand. Results of the present study suggest that LD mapping has potential for
      detecting a disease-associated variant on the basis of haplotype blocks.

PMID- 12506337
TI  - Obligate short-arm exchange in de novo Robertsonian translocation formation
      influences placement of crossovers in chromosome 21 nondisjunction.
AB  - Robertsonian translocations (ROBs) involving chromosome 21 are found in
      approximately 5% of patients with Down syndrome (DS). The most common
      nonhomologous ROB in DS is rob(14q21q). Aberrant recombination is associated with
      nondisjunction (NDJ) leading to trisomy 21. Haplotype analysis of 23 patients
      with DS and de novo rob(14q21q) showed that all translocations and all
      nondisjoined chromosomes 21 were maternally derived. Meiosis II NDJ occurred in
      21 of 23 families. For these, a ROB DS chromosome 21 genetic map was constructed
      and compared to a normal female map and a published trisomy 21 map derived from
      meiosis II NDJ. The location of exchanges differed significantly from both maps,
      with a significant shift to a more distal interval in the ROB DS map. The shift
      may perturb segregation, leading to the meiosis II NDJ in this study, and is
      further evidence for crossover interference. More importantly, because the event
      in the short arms that forms the de novo ROB influences the placement of
      chiasmata in the long arm, it is most likely that the translocation formation
      occurs through a recombination pathway in meiosis. Additionally, we have
      demonstrated that events that occur in meiosis I can influence events, such as
      chromatid segregation in meiosis II, many decades later.

PMID- 12506338
TI  - A whole-genome scan for obstructive sleep apnea and obesity.
AB  - Obstructive sleep apnea (OSA) is a common, chronic, complex disease associated
      with serious cardiovascular and neuropsychological sequelae and with substantial
      social and economic costs. Along with male gender, obesity is the most
      characteristic feature of OSA in adults. To identify susceptibility loci for OSA,
      we undertook a 9-cM genome scan in 66 white pedigrees (n=349 subjects)
      ascertained on the basis of either an affected individual with laboratory
      confirmed OSA or a proband who was a neighborhood control individual. Multipoint
      variance-component linkage analysis was performed for the OSA-associated
      quantitative phenotypes apnea-hypopnea index (AHI) and body mass index (BMI).
      Candidate regions on chromosomes 1p (LOD score 1.39), 2p (LOD score 1.64), 12p
      (LOD score 1.43), and 19p (LOD score 1.40) gave the most evidence for linkage to
      AHI. BMI was also linked to multiple regions, most significantly to markers on
      chromosomes 2p (LOD score 3.08), 7p (LOD score 2.53), and 12p (LOD score 3.41).
      Extended modeling indicated that the evidence for linkage to AHI was effectively
      removed after adjustment for BMI, with the exception of the candidate regions on
      chromosomes 2p (adjusted LOD score 1.33) and 19p (adjusted LOD score 1.45). After
      adjustment for AHI, the primary linkages to BMI remained suggestive but were
      roughly halved. Our results suggest that there are both shared and unshared
      genetic factors underlying susceptibility to OSA and obesity and that the
      interrelationship of OSA and obesity in white individuals may be partially
      explained by a common causal pathway involving one or more genes regulating both
      AHI and BMI levels.

PMID- 12506344
TI  - Co-expression and interaction of cubilin and megalin in the adult male rat
      reproductive system.
AB  - Cubilin is a peripheral membrane protein that cooperates with the endocytic
      receptor megalin to mediate endocytosis of ligands in various polarized
      epithelia. Megalin is expressed in the male reproductive tract where it has been
      implicated in the process of sperm membrane remodeling. A potential role for
      cubilin in the male reproductive tract has not been explored. Using RT-PCR, we
      found that cubilin and megalin mRNAs are expressed in the efferent ducts, corpus
      and cauda epididymis, and proximal and distal vas deferens. Immunohistological
      analysis revealed that cubilin was expressed in nonciliated cells of the efferent
      ducts, principal cells of the corpus and cauda epididymis and vas deferens.
      Immunogold EM showed cubilin in endocytic pits, endocytic vesicles, and endosomes
      of these cells. The expression profile of cubilin in the male reproductive tract
      was coincident with that of megalin except in principal cells of the caput
      epididymis. Double immunogold labeling showed that cubilin and megalin co
      localized within the endocytic apparatus and recycling vesicles of efferent duct
      cells. Neither protein was found in lysosomes. Injection of RAP, an antagonist of
      megalin interaction with cubilin, reduced the level of intracellular cubilin in
      cells of the efferent ducts and vas deferens. In conclusion, cubilin and megalin
      are co-expressed in cells of the epididymis and vas deferens and the endocytosis
      of cubilin in these tissues is dependent on megalin. Together, these findings
      highlight the potential for a joint endocytic role for cubilin and megalin in the
      male reproductive tract.

PMID- 12506345
TI  - Expression in Escherichia coli and immunological characterization of three zona
      pellucida proteins (ZP1, ZP2, and ZP3) from a marsupial, the brushtail possum
      (Trichosurus vulpecula).
AB  - The brushtail possum (Trichosurus vulpecula) zona pellucida (ZP) is composed of
      three major glycoproteins, designated ZP1, ZP2, and ZP3 based on their size and
      homology with eutherian ZP proteins. These proteins are candidate antigens for
      the development of an immunocontraceptive vaccine to control the fertility of the
      brushtail possum in New Zealand, where it is an introduced pest. In order to
      further their immunological and functional characterization, recombinant possum
      ZP proteins were produced in Escherichia coli (E. coli) strain JM109, M15,
      SG13009, or BL21 codon plus. Each of the proteins produced possessed a N-terminal
      six histidine tag (His)(6) to facilitate purification and consisted of amino acid
      (aa) residues 18-471 of possum ZP1, aa residues 40-311 of ZP2 (ZP2-N), aa
      residues 305-634 of ZP2 (ZP2-C), and aa residues 23-342 of ZP3. Immunoblot using
      anti-RGS(His)(4) antibodies and polyclonal rabbit anti-porcine ZP antibodies
      detected major bands at 54 kDa for ZP1, 32 kDa for ZP2-N, 39 kDa for ZP2-C, and
      40 kDa for ZP3. Immunization of male and female rabbits with ZP2-N, ZP2-C, and
      ZP3 purified on Ni-NTA resin under denaturing conditions generated antibodies
      reactive with recombinant ZP proteins on Western blot and with native ZP proteins
      in possum ovarian sections using immunofluorescence. Antibodies generated against
      ZP1 in the same way were reactive with recombinant ZP proteins on Western blot
      only. The recombinant possum ZP proteins and specific antibodies produced in this
      study give an indication of the antigenic relationship of the possum ZP proteins
      and are vital tools for future studies of sperm-ZP binding in marsupials and for
      the evaluation of ZP-based contraceptive vaccines in possums and other
      marsupials.

PMID- 12506346
TI  - Expression and location of taurine transporters and channels in the epididymis of
      infertile c-ros receptor tyrosine kinase-deficient and fertile heterozygous mice.
AB  - Defective sperm volume regulation causes infertility in c-ros knockout (KO) mice
      lacking the initial segment of the epididymis (IS). As taurine is in high
      concentration in the male tract and acts as an organic osmolyte in somatic cells,
      the taurine transporter (TauT), taurine content and taurine channel phospholemman
      (PLM) were examined in the epididymides of these and fertile heterozygous (+/-)
      mice. TauT and PLM genes were demonstrated by RT-PCR in the caput of +/- and c
      ros knockout males. Northern blots revealed one transcript of TauT (8 kb) in all
      regions with different expression between segments (cauda > corpus > IS > caput)
      and no differences in expression between genotypes. Western blotting revealed
      three translation products of TauT in all epididymal regions (107, 69, 49 kDa)
      with higher expression of the 69 kDa and 49 isoforms in the -/- than +/- caput.
      Immunohistochemical staining revealed staining of principal cells and stronger
      staining of apical and clear cells in all epididymal regions. The expression of
      the PLM transcript (0.75 kb: cauda = corpus > caput > IS) was upregulated in the
      proximal caput and cauda of KO mice. Tissue taurine was higher in the cauda
      >corpus>IS congruent with caput in fertile males and significantly higher in the
      proximal caput of the KO male. By contrast, taurine concentrations in cauda
      epididymidal fluid and content per 10(6) sperm did not differ between genotypes.
      TauT and PLM may be involved in taurine regulation in the normal epididymis and
      the proximal accumulation of taurine in the infertile males.

PMID- 12506347
TI  - Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa
      cells of dominant follicle in cattle.
AB  - The objective was to analyze gene expression in bovine granulosa cells of the
      dominant follicle by mRNA differential display. Total RNA was extracted from
      granulosa cells of <or=4 mm follicles, day 5 (D5) dominant follicles, and hCG
      induced preovulatory follicles. A differentially expressed cDNA observed in the
      dominant follicle group was used to screen a granulosa cell cDNA library, which
      resulted in the cloning of a 2,096 bp cDNA. Amino acid comparison showed identity
      level of 91.4, 83.9, and 83.1% when compared to human, rat, and mouse serine
      protease inhibitor E2, SERPINE2, also called Glia-derived nexin or protease Nexin
      1. A single transcript of 2.4 kb was shown to be differentially expressed in
      different bovine tissues. Immunoblotting with a specific antibody raised against
      a fragment of SERPINE2 (S(12)-R(196)) showed that SERPINE2 migrated at 47.5 kDa
      in support of glycosylation. Primordial, primary, and secondary pre-antral
      follicles showed immunostaining associated with granulosa cells and oocytes, and
      strong labeling in large antral follicles was located with granulosa cells and
      follicular fluid. Heterogeneity of SERPINE2 labeling was observed in CL. Semi
      quantitative real-time fluorescent RT-PCR showed a six-fold increase (P = 0.0002)
      in mRNA level of SERPINE2 in granulosa cells of D5 dominant follicle compared to
      granulosa cells collected from the <or=4 mm or preovulatory hCG-induced
      follicles. This report demonstrates that SERPINE2 mRNA is regulated in a spatio
      temporal pattern with highest levels in granulosa cells of growing dominant
      bovine follicles, and support the hypothesis that a high expression of SERPINE2
      may contribute to follicular growth whereas a decrease following hCG injection
      may contribute to ovulation.

PMID- 12506348
TI  - Changes of messenger RNAs encoding vascular endothelial growth factor and its
      receptors during the development and maintenance of caprine corpora lutea.
AB  - The present study was conducted to examine changes of mRNAs encoding vascular
      endothelial growth factor (VEGF) and its receptors (KDR/Flk-1 and Flt-1), and
      CD34, which is known to be a specific marker for endothelial cells, during the
      development and maintenance of the caprine corpora lutea (CL). Effects of a
      potent GnRH antagonist (GA), which was previously shown to suppress release of
      luteinizing hormone (LH), on expressions of those mRNAs during the CL development
      were also investigated. Goats were divided into control (n = 12) and GA-treated
      groups (n = 6). The goats were treated with saline or GA (50 microg/kg, sc) on
      days 0 (day of ovulation), 4, and 8 (control only), and CL collected on a subset
      of goats (n = 3 for each day) on days 0 (no saline), 4, 8, or 14 (control only).
      Ribonuclease protection assay was performed to quantitate the mRNAs in the CL
      using specific cRNA probes generated by RT-PCR and in vitro transcription. Level
      of CD34 mRNA significantly increased from day 0 to 8 (CL development) in the
      control group (P < 0.05). Long and short forms were detected in the caprine CL by
      RT-PCR for VEGF mRNA and analyses of their sequences showed that they correspond
      to mRNAs encoding VEGF(165) and VEGF(121), respectively. Level of VEGF(165) mRNA
      significantly increased from day 4 to 8 and day 8 to 14 (CL maintenance) in the
      control group (P < 0.05) while VEGF(121) mRNA did not change during the whole
      period. Level of KDR/Flk-1 mRNA significantly increased from day 0 to 8 (P <
      0.05) while Flt-1 mRNA significantly increased from day 8 to 14 (P < 0.005) in
      the control group. In the GA-treated group, levels of all of the mRNAs did not
      alter remarkably as compared with those in the control group. These results
      suggest that rise of KDR/Flk-1 and VEGF(165) mRNAs during the caprine CL
      development may be associated with enhanced angiogenesis and that increment of
      VEGF(165) and Flt-1 mRNAs during the CL maintenance may play nonangiogenic roles.
      The present study also indicates that the changes of VEGF(165) and KDR/Flk-1
      mRNAs during the CL development are probably not regulated by LH.

PMID- 12506349
TI  - Classical cadherin and catenin expression in normal myometrial tissues and
      uterine leiomyomas.
AB  - Uterine leiomyomas are the most common benign uterine tumors in the women of
      reproductive age. Previous studies have suggested that uterine leiomyomas are
      monoclonal tumors derived from a single neoplastic myometrial cell. However, the
      neoplastic transformation of myometrium to leiomyomas remains to be elucidated.
      The classical cadherins are a gene family of integral membrane glycoproteins that
      mediate calcium-dependent cell-cell adhesion in a homophilic manner. These cell
      adhesion molecules (CAMs) have been shown to play pivotal roles in tumorigenesis.
      Catenins are intracellular proteins that link the cytoplasmic domains of the
      cadherins to the cytoskeletons to promote the biological functions of these CAMs.
      In this study, we compared the expression of E-, N-, and P-cadherins and alpha-,
      beta-, and gamma-catenins in the uterine leiomyomas and the counterparts of
      normal myometrium of the same patients by using semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Of
      these, E-cadherin (E-cad) was not detected in both uterine leiomyomas and
      myometrium, P-cadherin (P-cad) was similarly expressed in these two tissues, but
      N-cadherin (N-cad) mRNA and protein expression levels in uterine leiomyomas were
      significantly greater than those observed in the myometrium. Catenins were not
      differentially expressed in uterine myometrium and leiomyomas. The overexpression
      of N-cad in uterine leiomyomas suggests that this CAM may play a central role in
      the development of uterine leiomyomas.

PMID- 12506350
TI  - Genetic mutation associated with meiotic metaphase-specific apoptosis in MRL/MpJ
      mice.
AB  - It has been reported that the MRL/MpJ mouse strain shows several unique
      phenotypes, including rapid wound healing, inherent collagen disease, heat shock
      resistant spermatocytes, and metaphase-specific apoptosis (Msa) in the testis. In
      the present study, we found the genetic mutation associated with Msa by
      chromosomal mapping with 555 backcross progeny. The Sertoli cell index of
      abnormal metaphasic spermatocytes was clearly divided into two groups in the
      first 200 male backcross progeny, which were created by mating female F1 (female
      C57BL/6 x male MRL/MpJ) with male MRL/MpJ mice, indicating that Msa was caused by
      only one gene. The result of chromosomal mapping throughout the 555 backcross
      progeny by using microsatellite markers and single nucleotide polymorphism (SNP)
      revealed that Msa was mapped on the telomeric region of chromosome 1 and was
      significantly linked with exonuclease 1 (Exo1) and choroideremia-like (rab escort
      protein 2) (Chml/Rep2) genes. It was found that the Chml/Rep2 gene was not a
      candidate for Msa by means of the nucleotide sequences of several inbred strains.
      On the Exo1 gene in strain MRL/MpJ, but not in other strains, it was surprisingly
      noted that the truncated forms (tr1-Exo1 and tr2-Exo1) were expressed in all
      tissues examined as well as normal Exo1 by reverse transcriptase-polymerase chain
      reaction (RT-PCR). Additionally, the truncated forms of the Exo1 gene were
      suggested to be transcribed by alternative splicing of the 9th exon, possibly
      resulting from nucleotide substitution of the branch site existing in the 8th
      intron. These results suggested that the testicular meiotic Msa in MRL/MpJ mice
      was a unique phenotype caused by incomplete alternative splicing of the Exo1
      gene.

PMID- 12506351
TI  - Calcium fluxes in human trophoblast (BeWo) cells: calcium channels, calcium
      ATPase, and sodium-calcium exchanger expression.
AB  - Although placental transfer of maternal calcium (Ca(2+)) is a crucial process for
      fetal development, the biochemical mechanisms are poorly understood. In the
      current study, we have investigated the characteristics of Ca(2+) fluxes in
      relation with cell Ca(2+) homeostasis in the human placental trophoblast cell
      line BeWo. Time-courses of Ca(2+) uptake by BeWo cells displayed rapid initial
      entry (initial velocity (V(i)) of 3.42 +/- 0.35 nmol/mg protein/min) and
      subsequent establishment of a plateau. Ca(2+) efflux studies with (45)Ca(2+)
      loaded cells also showed rapid declined of cell-associated (45)Ca(2+) with a V(i)
      of efflux (Ve(i)) of 3.30 +/- 0.08 nmol/mg protein/min. Further identification of
      membrane gates for Ca(2+) entry in BeWo cells was carried out. Expression of
      Ca(2+) transporter/channel CaT1 and L-type alpha(1S) subunit was showed by RT
      PCR. However, mRNA for CaT2 channel and L-type alpha(1C) and alpha(1D) subunits
      were not revealed. Membrane systems responsible for intracellular Ca(2+)
      extrusion from BeWo cells were also investigated. Plasma membrane Ca(2+)-ATPases
      (PMCA) and Na/Ca exchangers (NCX) were detected by Western blot in BeWo cells.
      Expression of specific isoforms of PMCA and NCX was further investigated by RT
      PCR. Messenger RNAs of four isoforms of PMCA (PMCA 1-4) were detected. The
      presence of messenger RNAs of two NCX isoforms (NCX1 and NCX3) was observed.
      Ca(2+) flux studies in Na-free incubation medium indicated that NCX played a
      minimal role in the cell Ca(2+) fluxes. Inorganic ions such as cadmium and
      manganese did not modify the Ca(2+) fluxes, however, barium increased cell
      associated (45)Ca(2+) by, in part, by reducing radiolabel exit.

PMID- 12506352
TI  - Isolation and partial characterization of three pregnancy-associated
      glycoproteins from the ewe placenta.
AB  - Pregnancy-associated glycoproteins (PAGs) are synthesized in the outer epithelial
      layer of the placenta in artiodactyls. In this work, three novel ovine PAGs were
      isolated from late-pregnancy fetal cotyledons and characterized biochemically.
      The isolation procedure included acid and ammonium sulfate precipitations and
      anion and cation exchange chromatographies. The isolated PAGs have different
      NH(2)-terminal amino acid sequences (RGSXLTILPLRNMRDIVY, ISRVSXLTIHPLRNIMDML, and
      RGSNLTIHPLRNIRD) and apparent molecular masses (55, 57, and 59 kDa). Each shows
      several isoforms with different pI values. The three proteins share high sequence
      identity with each other and with other ovine, bovine, and caprine PAGs. They
      have not been described previously. The ovPAG-59 sequence differs from the
      previously identified ovPAG-4 sequence (determined by DNA cloning and sequencing)
      at only one position among the 15 N-terminal residues. The newly characterized
      ovPAGs and the procedure used to isolate them will be helpful in producing new
      antisera for investigating PAG secretion in pregnant ewes.

PMID- 12506353
TI  - Resumption of metabolic activity of vitrified/warmed ovine embryos.
AB  - To evaluate resumption of metabolic activity of vitrified ovine embryos during a
      short time immediately after warming, blastocysts collected from superovulated
      Sarda ewes were incubated with (35)S-methionine. In vitrified/warmed embryo
      groups the protein secretion significantly (P < 0.05) increased from 0 to 24 hr
      of culture, reaching significantly (P < 0.01) higher activity at 18-24 hr and
      dropping to values similar to the control nonvitrified embryo group at 29-35 hr.
      Within the control group at 29-35 hr there was a significantly (P < 0.01) higher
      level of protein secretion compared to the other interval times. The
      electrophoretic pattern showed a 48-50 kDa secreted protein identified as
      urokinase-type plasminogen activator (PA). The caseinolytic assay of PA activity
      showed a course similar to protein secretion in both vitrified and control
      groups. During 29-35 hr of culture, we did not observe any improvement in PA
      activity as seen for secreted proteins. At this time, we observed the secretion
      of a new 20 kDa protein that was not present in vitrified/warmed embryos.
      Analysis of BrDU incorporation in newly synthesised DNA showed a significant (P <
      0.01) improvement in positive cell number from 3 to 9 hr after warming, reaching
      a value similar to that of the control group at 12 hr of culture. Our results
      suggest that vitrified/warmed embryos require 9-12 hr of culture to complete
      resumption of DNA synthesis and 29-35 hr to re-acquire the full capacity of
      protein secretion but not the qualitative secretion pattern.

PMID- 12506354
TI  - Capacity of adult and prepubertal mouse oocytes to undergo embryo development in
      the presence of cysteamine.
AB  - The present study was carried out to study de novo glutathione (GSH) synthesis
      and to evaluate the effect of stimulating GSH synthesis during in vitro
      maturation (IVM) of adult and prepubertal mouse oocytes on the embryo
      developmental rate. Adult (8 weeks old) and prepubertal mice (24-26 days old)
      were primed with 5 IU of PMSG and oocytes were retrieved from the ovary 48 hr
      later for IVM. After IVM (18 hr) Cumulus oocyte complexes (COC) were in vitro
      fertilized (IVF) and in vitro culture (IVC) in order to observe embryo
      development. The IVM medium was supplemented with: 0, 25, 50, 100, or 200 microM
      of cysteamine. To study the novo GSH synthesis, 5 mM BSO was added during IVM of
      adult or prepubertal oocyte. Developmental rates up to blastocyst were recorded
      for each group. Experiments also included a group of ovulated oocytes (in vivo
      matured) after priming with PMSG and HCG. After IVM of adult mice oocytes, an
      improvement was observed on embryo development in all the supplemented groups
      when compared with the untreated group (P < 0.05). No differences were observed
      in blastocyst rate among IVM oocytes with cysteamine and ovulated oocytes.
      Prepubertal IVM mouse oocytes had a lower cleavage rate compared with ovulated
      oocytes (P < 0.05). Cysteamine failed to improve prepubertal oocytes
      developmental rates (P > 0,05). 2-cell embryos, coming from IVM prepubertal
      oocytes and ovulated oocytes had the same preimplantation developmental rate up
      to the blastocyst stage. In prepubertal, and adult oocytes an inhibition of
      embryo development was observed when buthionine sulfoximide (BSO), a specific
      inhibitor of the gamma-glutamylcysteine synthetase, was added during oocyte
      maturation (P < 0.01). In conclusion, an improvement in mouse embryo development
      was observed when cysteamine was added to the IVM medium of adult mice oocytes.
      In prepubertal oocytes cysteamine addition during oocyte maturation failed to
      improve embryo developmental rates. The presence of BSO lowered or completely
      blocked blastocyst development. This proves that, de novo GSH synthesis during
      oocyte maturation of adult and prepubertal oocytes undoubtedly plays an important
      role in embryo development. The improvement on oocyte competence observed in
      adult mice oocytes is probably related to intracellular GSH synthesis stimulated
      by cysteamine. Nevertheless the reason why cysteamine failed to improve
      prepubertal oocytes competence remains as an open question.

PMID- 12506355
TI  - Optimization of superovulation induction by human menopausal gonadotropin in
      guinea pigs based on follicular waves and FSH-receptor homologies.
AB  - The guinea pig represents an excellent animal model for the study of reproduction
      in humans and most domestic animals because unlike the mouse and rat, it
      undergoes a complete estrous cycle. In this study, we investigated the
      availability of ovarian oocytes during the estrous cycle, and the follicle
      stimulating hormone (FSH) receptor (FSH-R) homologies between guinea pigs and
      other species, in order to identify an effective gonadotropin and optimal time-of
      application for the induction of superovulation in the guinea pig. The number of
      collectable ovarian oocytes showed biphasic changes with peaks at the midluteal
      and pre-ovulatory stages. On the other hand, the number of oocytes that matured
      in vitro remained constant ( approximately 10 oocytes) until day 14 post
      ovulation and increased thereafter. The deduced amino acid sequence of the guinea
      pig FSH-R showed greater similarity to the primate FSH-R than to the rodent FSH
      R, which suggests that commercially available human menopausal gonadotropin (hMG)
      may be a better inducer of superovulation in guinea pigs. Indeed, significantly
      more oocytes (5.4 +/- 1.6, range 0-17, n = 10) were obtained from hMG-treated
      guinea pigs at the pre-ovulatory stage than during spontaneous ovulation (3.6 +/-
      0.1, n = 96; P < 0.05), whereas guinea pigs that received hMG at the midluteal
      stage (n = 3) did not ovulate. These results indicate that hMG is an effective,
      albeit stage-dependent, inducer of superovulation in the guinea pig, and that FSH
      R homologies should be taken into account when choosing hormones for
      superovulation.

PMID- 12506356
TI  - Immunoglobulins against gp273, the ligand for sperm-egg interaction in the
      mollusc bivalve Unio elongatulus, are directed against charged O-linked
      oligosaccharide chains bearing a Lewis-like structure and interact with epitopes
      of the human zona pellucida.
AB  - In oocytes of the mollusc bivalve Unio elongatulus, gp273 is the ligand molecule
      for sperm-egg interaction and binding is mediated by its O-glycans. A serum
      raised against this protein enabled its localization in the crater region, the
      area of the vitelline coat where sperm recognition occurs, and showed that after
      cyanogen bromide fragmentation, the anti-gp273 epitope(s) was retained by a
      peptide where the O-glycans are localized. In this article, we utilized purified
      anti-gp273 immunoglobulins to characterize the corresponding epitope by: (i)
      immunoblotting analysis of the protein after removal of O- and N-glycans; (ii)
      solid phase binding analysis of anti-gp273 IgG to gp273 N- and O-glycans; and
      (iii) binding analysis of the same antibody to commercially available
      oligosaccharides. The results showed that the epitope consists of O-glycans and
      contains a Lewis-like structure with fucose as determinant. Anti-gp273 IgG were
      then used to investigate human zona pellucida by immunoelectronmicroscopy and
      immunoblotting. Epitopes recognized by the antibody were demonstrated on the
      outer surface of the zona pellucida and shown to belong to a zona pellucida
      protein having electrophoretic mobility similar to human ZP3. Since human sperm
      specifically bind to gp273, and anti-gp273 interferes with this binding a
      functional role for these epitopes is suggested.

PMID- 12506357
TI  - Sperm surface hyaluronan binding protein (HABP1) interacts with zona pellucida of
      water buffalo (Bubalus bubalis) through its clustered mannose residues.
AB  - Sperm-oocyte interaction during fertilization is multiphasic, with multicomponent
      events, taking place between zona pellucida (ZP) glycoproteins and sperm surface
      receptor. d-mannosylated glycoproteins, the major constituents of ZP are
      considered to serve as ligands for sperm binding. The presence of hyaluronan
      binding protein 1 (HABP1) on sperm surface of different mammals including cattle
      and its possible involvement in sperm function is already reported. Recently, we
      have demonstrated the specificity of clustered mannose as another ligand for
      HABP1 (Kumar et al., 2001: J Biosci 26:325-332). Here, we report that only N
      linked mannosylated zona-glycoproteins bind to sperm surface HABP1. Labeled HABP1
      interacts with ZP of intact oocyte of Bubalus bubalis, which can be competed with
      unlabeled HABP1 or excess d-mannosylated albumin (DMA). This data suggests the
      specific interaction of HABP1 with ZP, through clustered mannose residues. In
      order to examine the physiological significance of such an interaction, the
      capacity of sperm binding to oocytes under in vitro fertilization plates was
      examined either in presence of DMA alone or in combination with HABP1. The number
      of sperms, bound to oocytes was observed to reduce significantly in presence of
      DMA, which could be reversed by the addition of purified recombinant HABP1
      (rHABP1) in the same plate. This suggests that sperm surface HABP1 may act as
      mannose binding sites for zona recognition.

PMID- 12506358
TI  - Detection of DNA damage in bovine metaphase II oocytes resulting from
      cryopreservation.
AB  - Developmental competence of mammalian oocytes is compromised by currently
      available oocyte cryopreservation protocols. Experiments were designed to examine
      the effect of three cryopreservation protocols on the integrity of bovine oocyte
      DNA. In vitro matured bovine oocytes were cryopreserved either by slow cooling,
      vitrification in 0.25 ml straws, or in open pulled straws. After thawing/warming,
      recovered oocytes were immediately subjected to morphological evaluation.
      Morphologically intact oocytes underwent comet assay to detect cryoinjury at DNA
      level. All cryopreservation protocols resulted in significant morphological
      damage as well as DNA damage compared to unfrozen control. Among the
      morphologically intact oocytes, there was no difference among protocols in the
      number of oocytes displaying DNA damage. However, oocytes that had been
      cryopreserved by slow cooling or by vitrification in open pulled straws exhibited
      more damage than those vitrified in 0.25 ml straws in the extent of DNA damage.
      If we combine the number of oocytes with morphological damage and oocytes with
      DNA damage, oocytes cooled by slow cooling resulted in the most damage. This
      experiment demonstrated that oocyte DNA is a target of cryoinjury and different
      protocols result in different degrees of damage.

PMID- 12506361
TI  - Chiral relay: a novel strategy for the control and amplification of
      enantioselectivity in chiral Lewis acid promoted reactions.
AB  - Chiral Lewis acid catalysis has emerged as one of the premiere method to control
      stereochemistry. Much effort has gone into the design of superior ligands with
      increasing steric extension to shield distant reactive sites. We report here an
      alternative and complementary approach based on a "chiral relay". This strategy
      focuses on the improved design of achiral templates which may relay and amplify
      the stereochemistry from ligands. The essence of this strategy is that the chiral
      Lewis acid would effectively convert an achiral template into a chiral non
      racemic template. This approach combines the advantages of enantioselective
      catalysis (substoichiometric amount of the chiral inducer) with the ones of
      chiral auxiliary control (efficient and predictable stereocontrol).

PMID- 12506362
TI  - [60]Fullerene: a versatile photoactive core for dendrimer chemistry.
AB  - Owing to their special photophysical properties, fullerene derivatives are good
      candidates to demonstrate dendritic effects. In particular, the triplet lifetimes
      of a C(60) core can be used to evaluate its degree of isolation from external
      contacts. On the other hand, the fullerene core can act as a terminal energy
      receptor in dendrimer-based light-harvesting systems. When a fullerodendrimer is
      further functionalized with a suitable electron donor, it may exhibit the
      essential features of a multicomponent artificial photosynthetic system in which
      photoinduced energy transfer from the antenna to the C(60) core is followed by
      electron transfer.

PMID- 12506363
TI  - Crown ethers as ancillary ligands in the assembly of silver(i) aggregates
      containing embedded acetylenediide.
AB  - Five silver(I) double salts containing embedded acetylenediide, [Ag([12]crown
      4)(2)][Ag(10)(C(2))(CF(3)CO(2))(9)([12]crown-4)(2)(H(2)O)(3)] x H(2)O (2),
      [Ag(2)C(2) x 5 AgCF(3)CO(2) x (benzo[15]crown-5) x 2 H(2)O] x 0.5 H(2)O (3),
      [Ag(4)([18]crown-6)(4)(H(2)O)(3)][Ag(18)(C(2))(3)(CF(3)CO(2))(16)(H(2)O)(2.5)] x
      2.5 H(2)O (4), [Ag(2)C(2) x 6 AgC(2)F(5)CO(2) x 2([15]crown-5)](2) (5), and
      [(Ag(2)C(2))(2) x (AgC(2)F(5)CO(2))(9) x ([18]crown-6)(2) x (H(2)O)(3.5)] x H(2)O
      (6), have been isolated by varying the types of crown ethers and anions employed.
      Single-crystal X-ray analysis has shown that complex 2 is composed of winding
      anionic chains with sandwiched [Ag([12]crown-4)(2)](+) ions accommodated in the
      concave cavities between them. In 3, silver(I) double cages each sandwiched by a
      couple of benzo[15]crown-5 ligands are linked by [Ag(2)(CF(3)CO(2))(2)] bridges
      to form a one-dimensional structure. For 4, an anionic silver column is generated
      through fusion of two kinds of silver polyhedra (triangulated dodecahedron and
      bicapped trigonal antiprism), and the charge balance is provided by aqua-ligated
      [Ag([18]crown-6)](+) ions. Complex 5 is a centrosymmetric hexadecanuclear
      supermolecule composed of two [(eta(5)-[15]crown-5)(2)(C(2)@Ag(7))(mu
      C(2)F(5)CO(2))(5)] moieties connected through a [Ag(2)(C(2)F(5)CO(2))(2)] bridge.
      Compound 6 is a discrete supermolecule containing an asymmetric (C(2))(2)@Ag(13)
      cluster core capped by two [18]crown-6 ligands in mu(3)-eta(5) and mu(4)-eta(6)
      ligation modes.

PMID- 12506364
TI  - A fluorescent sensor for 2,3-bisphosphoglycerate using a europium tetra-N-oxide
      bis-bipyridine complex for both binding and signaling purposes.
AB  - Host 1 was designed and synthesized as a fluorescent sensor for 2,3
      bisphosphoglycerate (BPG, 3). The design features a tris-functionalized
      triethylbenzene core to preorganize binding groups. The three cationic moieties,
      a tetra-N-oxide bipyridine-europium complex and two ammonium groups, were
      included to complement the three anionic functionalities on the guest. Beyond
      acting as a binding site, the europium complex was used to signal binding of the
      guest through modification of the charge transfer emission. A 1:1 complex with
      BPG was determined in 50 % methanol/acetonitrile with a K(a) of 6.7 x 10(5) mol(
      1) by monitoring the reduction of the fluorescence signal upon guest addition. In
      the titration of related glycolytic intermediates lacking a second phosphate (4
      6) into host 1, 2:1 host to guest binding was observed. Similarly, control
      compound 2, which lacks the ammonium groups, binds BPG and 4-6 in a 2:1 fashion.
      Also, phenylphosphate 7 binds to host 1 in a 1:1 stoichiometry with a K(a) over
      three times less than 3.

PMID- 12506365
TI  - Fine tuning of photophysical properties of meso-meso-linked ZnII-diporphyrins by
      dihedral angle control.
AB  - A series of meso-meso-linked diporphyrins S(n) strapped with a dioxymethylene
      group of various length were synthesized by intramolecular Ag(I)-promoted
      coupling of dioxymethylene-bridged diporphyrins B(n), for n=10, 8, 6, 5, 4, 3, 2,
      and 1. Shortening of the strap length causes a gradual decrease in the dihedral
      angle between the porphyrins and increasing distortion of porphyrin ring, as
      suggested by MM2 calculations and (1)H NMR studies. This trend has been also
      suggested by X-ray crystallographic studies on the corresponding Cu(II) complexes
      of nonstrapped diporphyrin 2 Cu, and strapped diporphyrins S(8)Cu, S(4)Cu, and
      S(2)Cu. The absorption spectrum of relatively unconstrained diporphyrins S(10)
      strapped with a long chain exhibits split Soret bands at 414 and 447 nm and weak
      Q(0,0)- and prominent Q(1,0)-bands, both of which are similar to those of
      nonstrapped diporphyrin 2. Shortening of the strap length causes systematic
      changes in the absorption spectra, in which the intensities of the split Soret
      bands decrease, the absorption bands at about 400 nm and > 460 nm increase in
      intensity, and a prominent one-band feature of a Q-band is changed to a distinct
      two-band feature with concurrent progressive red-shifts of the lowest Q(0,0)
      band. The fluorescence spectra also exhibit systematic changes, roughly
      reflecting the changes of the absorption spectra. The strapped diporphyrins S(n)
      are all chiral and have been separated into enantiomers over a chiral column. The
      CD spectra of the optically active S(n) display two Cotton effects at 430-450 and
      at about 400 nm with the opposite signs. The latter effect can be explained in
      terms of oblique arrangement of m( perpendicular 1) and m( perpendicular 2)
      dipole moments, while the former effect cannot be accounted for within a
      framework of the excition coupling theory. The resonance Raman (RR) spectra taken
      for excitation at 457.9 nm are variable among S(n), while the RR spectra taken
      for excitation at 488.0 nm are constant throughout the S(n) series. These
      photophysical properties can be explained in terms of INDO/S-SCI calculations,
      which have revealed charge transfer (CT) transitions accidentally located close
      in energy to the excitonic Soret transitions. This feature arises from a close
      proximity of the two porphyrins in meso-meso-linked diporphyrins. In addition to
      the gradual red-shift of the exciton split Soret band, the calculations predict
      that the high-energy absorption band at about 400 nm, the lower energy Cotton
      effect, and the RR spectra taken for excitation at 457.9 nm are due to the CT
      states which are intensified upon a decrease in the dihedral angle.

PMID- 12506366
TI  - Electron-transfer chemistry of the iron-molybdenum cofactor of nitrogenase:
      delocalized and localized reduced states of FeMoco which allow binding of carbon
      monoxide to iron and molybdenum.
AB  - The electron-transfer chemistry of the isolated iron-molybdenum cofactor of
      nitrogenase (FeMoco) has been studied by electrochemical and
      spectroelectrochemical methods. Two interconverting forms of the cofactor arise
      from a redox-linked ligand isomerism at the terminal iron atom; this is
      attributed to rotamerism of an anionic N-methyl formamide ligand bound at this
      site. FeMoco in its EPR-silent oxidised state is shown to undergo three
      successive one-electron transfer steps. We argue that the first and second redox
      processes are associated with electron-transfer delocalised over the iron-sulfur
      core of the cofactor, whilst the third irreversible process is localised on
      molybdenum. This is strongly reinforced by spectroelectrochemical studies under
      (12)CO and (13)CO which reveal two independent carbon monoxide binding sites that
      are specifically associated with the second (iron core) and third (molybdenum)
      electron-transfer processes and which give rise to terminal nu((12)CO) bands at
      1885 and 1920 cm(-1) respectively. Moreover, in parallel with earlier studies on
      the enzyme system, it is shown that at low CO concentration, carbon monoxide
      binds to the cofactor in bridging modes, with nu(CO) bands at 1835 and 1808 cm(
      1) that are interconverted by single-electron transfer. Importantly we show that
      the contentious overall 2e difference in the assignment of the metal oxidation
      levels in the resting state of the enzyme-bound cofactor, arising from analysis
      of (57)Fe ENDOR and Mossbauer data, can be resolved in the light of the electron
      transfer chemistry of the isolated cofactor described herein.

PMID- 12506367
TI  - Convenient syntheses of fluorous aryl iodides and hypervalent iodine compounds:
      ArI(L)n reagents that are recoverable by simple liquid/liquid biphase workups,
      and applications in oxidations of hydroquinones.
AB  - Iodinations of the ortho, meta, and para fluorous arenes
      (R(f8)CH(2)CH(2)CH(2))(2)C(6)H(4) (R(f8)=(CF(2))(7)CF(3)) with I(2)/H(5)IO(6) in
      AcOH/H(2)SO(4)/H(2)O give 3,4-(R(f8)CH(2)CH(2)CH(2))(2)C(6)H(3)I (5) and the
      analogous 2,4- (6) and 2,5- (7) isomers, respectively. Spectroscopic yields are
      >90 %, but 5 and 7 must be separated by chromatography from by-products (yields
      isolated: 70 %, 97 %, 61 %). Reaction of 1,3,5-(R(f8)CH(2)CH(2)CH(2))(3)C(6)H(3)
      with PhI(OAc)(2)/I(2) gives 2,4,6-(R(f8)CH(2)CH(2)CH(2))(3)C(6)H(2)I (8) on
      multigram scales in 97 % yield. The CF(3)C(6)F(11)/toluene partition coefficients
      of 5-8 (24 degrees C: 69.5:30.5 (5), 74.7:25.3 (6), 73.9:26.1 (7), 98.0:2.0 (8))
      are lower than those of the precursors, but CF(3)C(6)F(11)/MeOH gives higher
      values (97.0:3.0 (5), 98.6:1.4 (6), 98.0:2.0 (7), >99.3:<0.3 (8)). Reactions of 5
      8 with excess NaBO(3) in AcOH yield the corresponding ArI(OAc)(2) species 9-12
      (9, 85 % as a 90:10 9/5 mixture; 10, 97 %; 11, 95 %; 12, 93 % as a 95:5 12/8
      mixture). These rapidly oxidize 1,4-hydroquinones in MeOH. Subsequent additions
      of CF(3)C(6)F(11) give liquid biphase systems. Solvent removal from the
      CF(3)C(6)F(11) phases gives 5-8 in >99-98 % yields, and solvent removal from the
      MeOH phases gives the quinone products, normally in >99-95 % yields. The
      recovered compounds 5-8 are easily reoxidized to 9-12 and used again.

PMID- 12506368
TI  - The final steps of the Oppolzer cyclization: mechanism of the insertion of
      alkenes into allylpalladium(II) complexes.
AB  - We report here the results of a computational study on the the mechanism of the
      Oppolzer cyclization. These results lead us to conclude that the insertion of
      olefins in Pd-allyl complexes probably takes place directly from the eta(3)-allyl
      species. The presence of a phosphane ligand in the reagents plays the role of
      enhancing the electron density on the Pd atom; this makes the alkene moiety more
      reactive towards insertion by back-donation from the metal. The results also
      indicate that the configuration of the new stereogenic centers is fixed in the
      insertion of the alkene into the (eta(3)-allyl)palladium species.

PMID- 12506369
TI  - Mechanism of dioxygen cleavage in tetrahydrobiopterin-dependent amino acid
      hydroxylases.
AB  - The reaction mechanism for the formation of the hydroxylating intermediate in
      aromatic amino acid hydroxylases (i.e., phenylalanine hydroxylase, tyrosine
      hydroxylase, tryptophan hydroxylase) was investigated by means of hybrid density
      functional theory. These enzymes use molecular oxygen to hydroxylate both the
      tetrahydrobiopterin cofactor and the aromatic amino acid. A mechanism is proposed
      in which dioxygen forms a bridging bond between the cofactor and iron. The
      product is an iron(II)-peroxy-pterin intermediate, and iron was found to be
      essential for the catalysis of this step. No stable intermediates involving a
      pterin radical cation and a superoxide ion O(2)(-) were found on the reaction
      pathway. Heterolysis of the O-O bond in the iron(II)-peroxy-pterin intermediate
      is promoted by one of the water molecules coordinated to iron and releases
      hydroxypterin and the high-valent iron oxo species Fe(IV)=O, which can carry out
      subsequent hydroxylation of aromatic rings. In the proposed mechanism, the
      formation of the bridging C-O bond is rate-limiting in the formation of Fe(IV)=O.

PMID- 12506370
TI  - Could redox-switched binding of a redox-active ligand to a copper(II) centre
      drive a conformational proton pump gate? A synthetic model study.
AB  - A proposal for a redox-linked conformational gate to proton translocation--a
      proton pump gate--based upon a transition-metal redox-switchable hemilabile
      ligand (RHL) system is made. Consideration of the requirements for such a system
      reveals copper(II) to be the ideal metal centre. To test the proposal and,
      thereby, to provide an artificial proton pump gate, the copper coordination
      chemistry of three tris(pyridylmethyl)amine (tpa) ligands with one "leg" (PY*)
      substituted at the 6-position of the pyridine ring by a dimethoxyphenyl (L(1)), a
      hydroquinone (H(2)L(2)) or a quinone (L(3)) substituent has been investigated.
      Crystal structures of sp-[Cu(kappa(4)N-L(1))Cl]Cl.3 H(2)O (sp=square pyramidal),
      sp-[Cu(kappa(3)N-H(2)L(2))Cl(2)] and tbp-[Cu(kappa(4)N,kappaO-HL(2))][PF(6)]
      (tbp=trigonal bipyramidal) have been determined. The Cu(I) complexes
      [Cu(L)(MeCN)(n)](+) (L=L(1), H(2)L(2)) display physicochemical properties
      consistent with a "dangling" PY* leg; from the NMR spectra, the barriers to
      inversion of the ligand amine donor for the Cu(I) complexes are estimated to be
      within the range of about 30-45 kJ mol(-1). In the Cu(II) complexes, coordination
      of the PY* leg is finely balanced and critically depends on the nature of the PY*
      substituent and the availability of potential co-ligand(s). For example, tbp
      [Cu(kappa(4)N-L(1))Cl](+) reacts cleanly with Cl(-) ions to afford sp
      [Cu(kappa(3)N-L(1))Cl(2)]; Vis/NIR spectrophotometric titrations suggest the
      affinity of tbp-[Cu(kappa(4)N-L(1))Cl](+) for Cl(-) ion in dichloromethane is 9.7
      x 10(2) and is at least 10(4)-fold greater than that of tbp-[Cu(kappa(4)N
      L(3))Cl](+). The complex sp-[Cu(kappa(3)N-H(2)L(2))Cl(2)] has a "dangling" PY*
      leg, in which an intramolecular OH(hydroquinone).N(pyridine) hydrogen bond "ties
      up" the pyridyl nitrogen atom, and reacts with Bronsted bases to give tbp
      [Cu(kappa(4)N,kappaO-HL(2))](+). Two-electron oxidation of sp-[Cu(kappa(3)N
      H(2)L(2))Cl(2)] is linked to loss of two protons and a conformational change, and
      affords tbp-[Cu(kappa(4)N-L(3))Cl](+). The [Cu(kappa(3)N-H(2)L(2))Cl(2)]
      [Cu(kappa(4)N-L(3))Cl](+) system provides a first demonstration of the critical
      step in the proposed proton pumping cycle, namely a redox-driven and proton
      linked conformational change. The possible biological relevance of this work to
      proton pumping in cytochrome c oxidase is mentioned.

PMID- 12506371
TI  - Guest binding and orientation within open nanoscale hosts.
AB  - The synthesis of three different nanoscale molecular hosts is reported. These
      cavitands each possess a highly preorganized cavity with an open portal (nearly 1
      nm wide), by which guests can enter and egress the cavity. Additionally, these
      hosts are deep-functionalized with a crown of weakly acidic benzal C-H groups
      which can form a variety of noncovalent interactions with guest molecules
      residing within the cavity. Thirty-one guests were examined for their propensity
      to form complexes with the hosts. Guests that possess halogen atoms were the
      strongest binders, suggesting the formation of polydentate C-H triplebond X-R
      hydrogen bonds with the deep crown of benzal hydrogens. Exchange rates between
      the free and bound states were noted to be dependent on the size of the guest and
      the solvent used to study complexation. In general, stronger binding and slower
      exchange were noted for complexations carried out in DMSO with highly
      complementary guests. The orientation of each guest within the cavity was
      determined using either EXSY NMR spectroscopy or (1)H NMR shift data.
      Cumulatively these results showed that the principal factors directing
      orientation were interactions with the benzal groups and the type of solvent.
      Van't Hoff analyses of selected complexations were also carried out. As well as
      revealing that all complexations were entropically unfavorable, these experiments
      provided support for guest orientation determinations, and gave an estimation
      that the formation of a C-H triplebond I-R hydrogen bond releases between 1 and
      1.5 kcal mol(-1).

PMID- 12506372
TI  - Modular synthesis of heparin oligosaccharides.
AB  - A general, modular strategy for the first completely stereoselective synthesis of
      defined heparin oligosaccharides is described. Six monosaccharide building blocks
      (four differentially protected glucosamines, one glucuronic and one iduronic
      acid) were utilized to prepare di- and trisaccharide modules in a fully selective
      fashion. Installation of the alpha-glucosamine linkage was controlled by placing
      a conformational constraint on the uronic acid glycosyl acceptors thereby
      establishing a new concept for stereochemical control. Combination of
      disaccharide modules to form trans-uronic acid linkages was completely selective
      by virtue of C2 participating groups. Coupling reactions between disaccharide
      modules exhibited sequence dependence. While the union of many glucosamine uronic
      acid disaccharide modules did not meet any problems, certain sequences proved not
      accessible. Elaboration of glucosamine uronic acid disaccharide building blocks
      to trisaccharide modules by addition of either one additional glucosamine or
      uronic acid allowed for stereoselective access to oligosaccharides as
      demonstrated on the example of a hexasaccharide resembling the ATIII-binding
      sequence. Final deprotection and sulfation yielded the fully synthetic heparin
      oligosaccharides.

PMID- 12506373
TI  - Formation and chemical reactivities of a new type of double-butterfly [[Fe2(mu
      CO)(CO)6]2(mu-SZS-mu)]2-: synthetic and structural studies on novel linear and
      macrocyclic butterfly Fe/E (E=S, Se) cluster complexes.
AB  - A new type of double-butterfly [[Fe(2)(mu-CO)(CO)(6)](2)(mu-SZS-mu)](2-) (3), a
      dianion that has two mu-CO ligands, has been synthesized from dithiol HSZSH
      (Z=(CH(2))(4), CH(2)(CH(2)OCH(2))(1-3)CH(2)), [Fe(3)(CO)(12)], and Et(3)N in a
      molar ratio of 1:2:2 at room temperature. Interestingly, the in situ reactions of
      dianions 3 with various electrophiles affords a series of novel linear and
      macrocyclic butterfly Fe/E (E=S, Se) cluster complexes. For instance, while
      reactions of 3 with PhC(O)Cl and Ph(2)PCl give linear clusters [[Fe(2)(mu
      PhCO)(CO)(6)](2)(mu-SZS-mu)] (4 a,b: Z=CH(2)(CH(2)OCH(2))(2,3)CH(2)) and
      [[Fe(2)(mu-Ph(2)P)(CO)(6)](2)(mu-SZS-mu)] (5 a,b:
      Z=CH(2)(CH(2)OCH(2))(2,3)CH(2)), reactions with CS(2) followed by treatment with
      monohalides RX or dihalides X-Y-X give both linear clusters [[Fe(2)(mu
      RCS(2))(CO)(6)](2)(mu-SZS-mu)] (6 a-e: Z=CH(2)(CH(2)OCH(2))(1,2)CH(2); R=Me,
      PhCH(2), FeCp(CO)(2)) and macrocyclic clusters [[Fe(2)(CO)(6)](2)(mu-SZS-mu)(mu
      CS(2)YCS(2)-mu)] (7 a-e: Z=(CH(2))(4), CH(2)(CH(2)OCH(2))(1-3)CH(2); Y=(CH(2))(2
      4), 1,3,5-Me(CH(2))(2)C(6)H(3), 1,4-(CH(2))(2)C(6)H(4)). In addition, reactions
      of dianions 3 with [Fe(2)(mu-S(2))(CO)(6)] followed by treatment with RX or X-Y-X
      give linear clusters [[[Fe(2)(CO)(6)](2)(mu-RS)(mu(4)-S)](2)(mu-SZS-mu)] (8 a-c:
      Z=CH(2)(CH(2)OCH(2))(1,2)CH(2); R=Me, PhCH(2)) and macrocyclic clusters
      [[[Fe(2)(CO)(6)](2)(mu(4)-S)](2)(mu-SYS-mu)(mu-SZS-mu)] (9 a,b:
      Z=CH(2)(CH(2)OCH(2))(2,3)CH(2); Y=(CH(2))(4)), and reactions with SeCl(2) afford
      macrocycles [[Fe(2)(CO)(6)](2)(mu(4)-Se)(mu-SZS-mu)] (10 d:
      Z=CH(2)(CH(2)OCH(2))(3)CH(2)) and [[[Fe(2)(CO)(6)](2)(mu(4)-Se)](2)(mu-SZS
      mu)(2)] (11 a-d: Z=(CH(2))(4), CH(2)(CH(2)OCH(2))(1-3)CH(2)). Production pathways
      have been suggested; these involve initial nucleophilic attacks by the Fe
      centered dianions 3 at the corresponding electrophiles. All the products are new
      and have been characterized by combustion analysis and spectroscopy, and by X-ray
      diffraction techniques for 6 c, 7 d, 9 b, 10 d, and 11 c in particular. X-ray
      diffraction analyses revealed that the double-butterfly cluster core Fe(4)S(2)Se
      in 10 d is severely distorted in comparison to that in 11 c. In view of the Z
      chains in 10 a-c being shorter than the chain in 10 d, the double cluster core
      Fe(4)S(2)Se in 10 a-c would be expected to be even more severely distorted, a
      possible reason for why 10 a-c could not be formed.

PMID- 12506374
TI  - A family of Group 4 metal alkoxo complexes with an M3(mu3-O) core relevant to
      Ziegler-Natta catalyst intermediates.
AB  - Reactions of [Mg(thffo)(2)] (1) or [Ca(thffo)(2)] (2) with ZrCl(4) or HfCl(4) in
      a CH(2)Cl(2)/THF/CH(3)CN mixture give thermally stable neutral heterobimetallic
      tetranuclear complexes [M(3)M'(mu(x)-O)(mu,eta(2)-thffo)(6)(Cl)(6)]
      (thffo=tetrahydrofurfuroxide; M/M'/x: 3, Zr/Mg/3; 4, Hf/Mg/3; 5, Zr/Ca/4; 6,
      Hf/Ca/4) as colorless crystals in 75-82 % yield. X-ray diffraction studies show
      complexes 3-5 to contain oxo-bridged M(3) triangles that are capped by an
      alkaline earth metal-containing moiety to form species of C(3) symmetry.
      Reactions of ZrCl(4) and HfCl(4) with pure tetrahydrofurfuryl alcohol in EtOH and
      MeOH provide ionic complexes [M(3)(mu(3)-O)(mu,eta(2)-thffo)(3)(L)(3)(Cl)(6)]Cl
      (M/L: 8, Zr/EtOH; 9, Hf/EtOH; 10, Zr/MeOH) in 66-79 % yield. Complexes 8-10
      consist of M(3) triangles that are analogous to those in 3-6 and possess similar
      overall symmetry, as shown by X-ray crystallography. Changes in the reaction
      conditions afforded the asymmetric neutral dimer [Zr(2)(mu
      thffo)(2)(thffoH)(Cl)(6)] (7) and the homometallic [Zr(3)(mu(3)-O)(mu,eta(2)
      thp)(3)(thf)(2)(Cl)(7)] (11).

PMID- 12506375
TI  - How to turn the catalytic asymmetric hydroboration reaction of vinylarenes into a
      recyclable process.
AB  - Optically pure rhodium(I) complexes [Rh(cod)(Lbond;L)]X (cod=cyclooctadiene; L-L=
      (R)-2,2'-bis(diphenylphosphino)1-1'-binaphthyl ((R)-BINAP), (S,S)-2,4
      bis(diphenylphosphino)pentane ((S,S)-BDPP), 2-diphenylphosphino-1-(1'
      isoquinolyl)naphthalene ((S)-QUINAP); X=BF(4), PF(6), SO(3)CF(3), BPh(4)) were
      immobilised onto smectite clays such as montmorillonite K-10 (MK-10) and
      bentonite (Na(+)-M). (19)F, (31)P and (11)B NMR experiments recorded in CDCl(3)
      during the impregnation process provided evidence that montmorillonite K-10 may
      immobilise ionic metal complexes throughout the cationic and anionic
      counterparts. However, when bentonite was used as the solid, only the cationic
      metal complex was immobilised through cationic exchange while the counteranion
      remained in solution. When we used these preformed catalytic systems in the
      hydroboration of prochiral vinylarenes, we obtained high activities and
      enantiomeric excess with (S)-1-(2-diphenylphosphino-1-naphthyl)isoquinoline
      modified rhodium complexes. These activities and selectivities are competitive
      with the homogeneous counterparts. The significant features of this method are
      the simple separation and good retention of the active metal in the solid, which
      allows efficient recycling even on exposure to air.

PMID- 12506376
TI  - Mono- and binuclear ruthenium corroles: synthesis, spectroscopy,
      electrochemistry, and structural characterization.
AB  - The aim of this research was to prepare mononuclear ruthenium corroles, because
      of the well-documented potency of analogous porphyrin complexes in catalysis. The
      syntheses of the mononuclear nitrosyl complexes [Ru(tpfc)(NO)] and [Ru(tdcc)(NO)]
      (tpfc=trianion of 5,10,15-tris(pentafluorophenyl)corrole, tdcc=trianion of
      5,10,15-tris(2,6-dichlorophenyl)corrole), and of the binuclear [[Ru(tpfc)](2)]
      were achieved by using [[Ru(cod)Cl(2)](x)] (cod=cyclooctadiene) as the metal
      source. The NMR spectra of all three complexes clearly demonstrate that they are
      diamagnetic; this is consistent with a triple bond between the metal ions in
      [[Ru(tpfc)](2)] and is expected for classical [MNO](6) complexes. These features
      were further substantiated by the stretching frequencies of the [MNO] moieties,
      electrochemical measurements on all complexes, and the X-ray crystal structures
      of [Ru(tpfc)(NO)] and [[Ru(tpfc)](2)]. A comparison of the spectroscopic and
      structural characteristics of these new complexes with analogous iron corroles,
      as well as with iron and ruthenium porphyrins, suggests that it will be hard to
      obtain mononuclear ruthenium corroles without pi-accepting ligands.

PMID- 12506377
TI  - Metal catalysis inside polymer frameworks: evaluation of catalyst stability and
      reusability.
AB  - The polymer framework of a resin-based catalyst built up with Pd nanoclusters
      (ca. 3 nm) dispersed inside the nanoporous domains of a thermally stable gel-type
      polyacrylic resin exhibits a good chemical stability under 5 bar H(2) at 40
      degrees C for reasonable contact times. Chemical and physico-chemical integrity
      of the polymer framework are checked with a variety of instrumental analytical
      methods. Catalyst reusability turns out to be quite good.

PMID- 12506378
TI  - Naphthalene-1,8-diyl bis(halogenophosphanes): novel syntheses and structures of
      useful synthetic building blocks.
AB  - A series of new bay region disphospha-functionalised naphthalenes is reported.
      The reduction of ylidic phosphonium phosphoride NapP(2)Cl(6) (1) (Nap=naphthalene
      1,8-diyl) with MeOPCl(2) gives the important synthon Nap(PCl(2))(2) (2) in nearly
      quantitative yield. Reaction of 1 with magnesium metal affords (NapP(2))(n) (3),
      which reacts with Br(2) and I(2), yielding Nap(PBr(2))(2) (4) and Nap(PI)(2) (5),
      respectively. X-ray structure determinations reveal a twisted geometry of the
      naphthalene ring in sterically strained 2 and 4, whilst the presence of a P-P
      bond in 5 results in the release of the steric strain and generation of the
      planar NapP(2) moiety. Although the tetrahedral P environments are severely
      distorted the sigma(3)P-sigma(3)P bonding in 5 represents a new type of P-P
      bonding environment in 1,8-diphosphanaphthalenes. Compounds 1, 4 and 5 each
      represent the highest coordination, achievable by direct halogenation. The new
      compounds 2-5 were fully characterised by NMR, IR, and Raman spectroscopy, mass
      spectrometry, and elemental analysis.

PMID- 12506379
TI  - Voltage-dependent formation of anion channels by synthetic rigid-rod push-pull
      beta-barrels.
AB  - Ion channels formed by p-octiphenyls equipped with amphiphilic, cationic
      tripeptide strands and either with (5) or without (6) axial dipole moment are
      described (preliminary communication: N. Sakai, S. Matile, J. Am. Chem. Soc.
      2002, 124, 1184-1185). Fluorescence kinetics with variably polarized neutral or
      anionic vesicles, together with planar bilayer conductance measurements, reveal
      voltage dependence with weakly lyotropic anion selectivity, and deactivation by
      competing surface potentials of the ion channels formed by asymmetric 5. In
      planar bilayers, 5 forms short-lived, poorly organized channels--similar to those
      produced by alpha-helical natural antibiotics--capable of transforming into
      stable, ohmic p-octiphenyl "beta-barrel" ion channels similar to those of the >99
      % homologous but symmetric 6. Fluorescence depth quenching and circular dichroism
      studies confirm the effect of membrane potentials in promotion of the
      partitioning of 5 (but not 6) into the bilayers, identifying partitioning as the
      voltage-dependent step.

PMID- 12506380
TI  - High thermodynamic stability and extraordinary kinetic inertness of copper(II)
      complexes with 1,4,8,11-tetraazacyclotetradecane-1,8-bis(methylphosphonic acid):
      example of a rare isomerism between kinetically inert penta- and hexacoordinated
      copper(II) complexes.
AB  - In an aqueous solution at room temperature, 1,4,8,11-tetraazacyclotetradecane-1,8
      bis(methylphosphonic acid) (H(4)L(1)) and Cu(I) (I) form a pentacoordinated (pc)
      complex, pc-[Cu(L(1))](2-), exhibiting conformation I of the cyclam ring. At high
      temperature, the complex isomerises to a hexacoordinated isomer, trans-O,O
      [Cu(L(1))](2-), with a trans-III conformation of the cyclam ring. In pc
      [Cu(L(1))](2-), four ring nitrogen atoms and one phosphonate oxygen atom are
      arranged around Cu(I) (I) in a structure that is half-way between a trigonal
      bipyramid and a tetragonal pyramid, with one phosphonic acid group uncoordinated.
      In the trans-O,O-[Cu(L(1))](2-) isomer, the nitrogen atoms form a plane and the
      phosphonic acid groups are in a mutually trans configuration. A structurally very
      similar ligand, 4-methyl-1,4,8,11-tetraazacyclotetradecane-1,8
      bis(methylphosphonic acid) (H(4)L(2)), forms an analogous pentacoordinated
      complex, pc-[Cu(L(2))](2-), at room temperature. However, the complex does not
      isomerise to the octahedral complex analogous to trans-O,O-[Cu(L(1))](2-).
      Because of the high thermodynamic stability of pc-[Cu(L(1))](2-),
      (logbeta=25.40(4), 25 degrees C, I=0.1 mol dm(-3) KNO(3)) and the formation of
      protonated species, Cu(I) (I) is fully complexed in acidic solution (-log [H(+)]
      approximately 3). Acid-assisted decomplexation of both of the isomers of
      [Cu(H(2)L(1))] takes place only after protonation of both uncoordinated oxygen
      atoms of each phosphonate moiety and at least one nitrogen atom of the cycle. The
      exceptional kinetic inertness of both isomers is illustrated by their half-lives
      tau(1/2)=19.7 min for pc-[Cu(H(2)L(1))] and tau(1/2) about seven months for trans
      O,O-[Cu(H(2)L(1))] for decomplexation in 5 M HClO(4) at 25 degrees C. The
      mechanism of formation of pc-[Cu(L(1))](2-) is similar to those observed for
      other macrocyclic complexes.

PMID- 12506381
TI  - Amination of benzylic C-H bonds by arylazides catalyzed by CoII-porphyrin
      complexes: a synthetic and mechanistic study.
AB  - Co(II)-porphyrin complexes catalyze the reaction of aromatic azides (ArN(3)) with
      hydrocarbons that contain a benzylic group (ArR(1)R(2)CH) to give the
      corresponding amines (ArR(1)R(2)C-NHAr). When at least one of the R substituents
      is hydrogen, the catalytic reaction proceeds further to give the imine ArRC=NAr
      in good yields. The reaction mechanism has been investigated. The reaction
      proceeds through a reversible coordination of the arylazide to the Co(II)
      porphyrin complex. This unstable adduct can either react with the hydrocarbon in
      the rate-determining step or decompose by a unimolecular mechanism to afford a
      putative "nitrene" complex, which reacts with more azide, but not with the
      hydrocarbon, to afford the byproduct diaryldiazene. The kinetics of the catalytic
      reaction have been investigated for a range of azides and substituted toluenes.
      Arylazides with electron-withdrawing substituents react at a faster rate and a
      good correlation is found between the log(k) and the Taft parameters. On the
      other hand, an excellent correlation between the logarithm of the rate for
      substituted toluenes relative to that of toluene and a radical parameter
      (sigma*JJ) alone was found, with no significant contribution by polar parameters.
      An explanation has been proposed for this anomalous effect and for the very high
      isotopic effect (k(H)/k(D)=14) found.

PMID- 12506382
TI  - Enantioselective synthesis of paraconic acids.
AB  - The development of a new method for the enantioselective synthesis of
      disubstituted gamma-butyrolactones is reported. Based on this strategy, the total
      synthesis of three paraconic acids, that is (-)-roccellaric acid, (-)
      nephrosteranic acid and (-)-protopraesorediosic acid, and the formal total
      synthesis of (-)-methylenolactocin and (-)-protolichesterinic acid is described,
      which are important because of their antibiotic and antitumor properties. Key
      steps of the synthesis are copper(I)-catalyzed asymmetric cyclopropanations of
      furans, highly diastereoselective Sakurai allylations, Lewis acid or Lewis base
      catalyzed retroaldol/lactonization cascades, and ruthenium(II)-catalyzed,
      intermolecular cross metathesis reactions.

PMID- 12506383
TI  - Chemistry of phosphine-borane adducts at platinum centers: synthesis and
      reactivity of PtII complexes with phosphinoborane ligands.
AB  - Reaction of [Pt(PEt(3))(3)] with the primary and secondary phosphine-borane
      adducts PhRPH x BH(3) (R=H, Ph) resulted in oxidative addition of a P-H bond at
      the Pt(0) center to afford the complexes trans-[PtH(PPhR x BH(3))(PEt(3))(2)] (1:
      R=H; 2: R=Ph). The products 1 and 2 were characterized by (1)H, (11)B, (13)C,
      (31)P, and (195)Pt NMR spectroscopy, and the molecular structures were verified
      by X-ray crystallography. In both cases, a trans arrangement of the hydride
      ligand with respect to the phosphidoborane ligand was observed. When 2 was
      treated with PhPH(2) x BH(3), a novel phosphidoborane ligand-exchange reaction
      occurred which yielded 1 and Ph(2)PH x BH(3). Treatment of 2 with one equivalent
      of depe (depe=1,2-bis(diethylphosphino)ethane) resulted in the formation of the
      complex cis-[PtH(PPh(2) x BH(3))(depe)] (3), in which the hydride ligand and the
      phosphidoborane ligand are in a cis arrangement. Treatment of 3 with PhPH(2) x
      BH(3) was found to result in an exchange of the phosphidoborane ligands to give
      the complex cis-[PtH(PPhH x BH(3))(depe)] (4) and Ph(2)PH x BH(3). Complex 4 was
      found to undergo further reaction in the presence of PhPH(2) x BH(3) to give meso
      cis-[Pt(PPhH x BH(3))(2)(depe)] (5) and rac-cis-[Pt(PPhH x BH(3))(2)(depe)] (6).

PMID- 12506384
TI  - Studies on mimicry of naturally occurring annonaceous acetogenins: non-THF
      analogues leading to remarkable selective cytotoxicity against human tumor cells.
AB  - A class of structurally simplified analogues of the naturally occurring
      annonaceous acetogenins were developed, amongst which some non-THF analogues
      showed remarkable cytotoxicities against tumor cell lines, as well as good
      selectivity between human tumor cells and normal cells. The synthetic routes were
      significantly shortened because of the removal of the chiral centers bearing the
      THF rings on the natural templates. This simplification also provides access to
      the parallel synthesis of these mimics by a combinatorial strategy. The remaining
      stereogenic centers at the positions alpha to the ethereal links were introduced
      by the Chiron approach from the easily accessible chiral building blocks 6a
      and/or 6b, made in turn from L-ascorbic acid or D-mannitol, while the one in the
      butenolide segment was taken from L-lactate. All four diastereomeric non-THF
      analogues 2a-2d showed remarkable activity against the HCT-8 cell line, and
      better differentiation was found when testing against the HT-29 cell line. It was
      also discovered that both the butenolide and ethylene glycol subunits play
      essential roles in the cytotoxicities against tumor cell lines, while the 10
      substituted hydroxy group and the absolute configuration of methyl group at the
      butenolide moiety are less important for their activity.

PMID- 12506385
TI  - Functional supramolecular devices: [M4IIL4]8+ [2 x 2]-grid-type complexes as
      multilevel molecular electronic species.
AB  - The [M(4)(II)L(4)](8+) [2 x 2]-grid-type complexes 1-8 present a set of features
      of particular interest for potential applications. All complexes exhibit multiple
      reduction levels at low reduction potentials paired with rather high stability.
      The modulation of the reduction potentials is possible by introduction of
      appropriate substituents on the ligands. The Co(II)(4) complexes 1-5 present a
      remarkable regularity in the disposition of the reduction levels, indicating the
      ability of the Co(II) sites to transmit electronic interactions between reduced
      ligands. In general, all investigated molecular systems 1-8 show characteristics
      typical for multilevel supramolecular electronic devices.

PMID- 12506386
TI  - Synthesis and formation mechanism of manganese dioxide nanowires/nanorods.
AB  - Alpha-, beta-, gamma-, and delta-MnO(2) single-crystal nanowires/nanorods with
      different aspect ratios have been successfully prepared by a common hydrothermal
      method based on the redox reactions of MnO(4)(-) and/or Mn(2+). The influences of
      oxidant, temperature, and inorganic cation (NH(4)(+) and K(+)) template
      concentrations on the morphology and crystallographic forms of the final products
      are discussed in this paper. It is interesting to find that all the MnO(2) one
      dimensional nanostructures have a similar formation process: delta-MnO(2), which
      has a layer structure, serves as an important intermediate to other forms of
      MnO(2), and is believed to be responsible for the initial formation of MnO(2) one
      dimensional nanostructures. A rolling mechanism has been proposed based on the
      results of the series of TEM images and XRD patterns of the intermediate.

PMID- 12506387
TI  - Total synthesis of woodrosin I--part 1: preparation of the building blocks and
      evaluation of the glycosylation strategy.
AB  - The preparation of three building blocks required for the total synthesis of
      woodrosin I (1) is outlined, a complex resin glycoside bearing a macrolide ring
      which spans four of the five sugars of its oligosaccharide backbone. Key steps
      involve the enantioselective, titanium-catalyzed addition of dipentylzinc to 5
      hexenal, the glycosylation of the resulting alcohol 18 with the glucose-derived
      trichloroacetimidate 7, and further elaboration of the resulting product 19 into
      disaccharide 22 on treatment with the orthogonally protected glycosyl donor 15.
      The trichloroacetimidate method is also used for the formation of the second
      synthon represented by disaccharide 38. A model study shows that the assembly of
      the pentasaccharidic perimeter of 1 depends critically on the phasing of the
      glycosylation events between fragments 22, 38 and the rhamnosyl donor 27 due to
      the severe steric hindrance in the product. A particularly noteworthy finding is
      the fact that diol 22 can be regioselectively glycosylated at the 3'-OH group in
      high yield without protection of the neighboring 2'-OH function.

PMID- 12506388
TI  - Total synthesis of woodrosin I--part 2: final stages involving RCM and an
      orthoester rearrangement.
AB  - The completion of the first total synthesis of the complex resin glycoside
      woodrosin I (1) is outlined using the building blocks described in the preceding
      paper. Key steps involve the TMSOTf-catalyzed coupling of diol 2 with
      trichloroacetimidate 3 which leads to the selective formation of orthoester 5
      rather than to the expected tetrasaccharide. Diene 5, on treatment with catalytic
      amounts of the Grubbs carbene complex 6 or the phenylindenylidene ruthenium
      complex 7, undergoes a high yielding ring closing olefin metathesis reaction
      (RCM) to afford macrolide 8. Exposure of the latter to the rhamnosyl donor 4 in
      the presence of TMSOTf under "inverse glycosylation" conditions delivers compound
      9 by a process involving glycosylation of the sterically hindered 2'-OH group and
      concomitant rearrangement of the adjacent orthoester into the desired beta
      glycoside. This transformation constitutes one of the most advanced applications
      of the Kochetkov glycosidation method reported to date. Cleavage of the
      chloroacetate followed by exhaustive hydrogenation completes the total synthesis
      of the targeted glycolipid 1.

PMID- 12506389
TI  - The molecular structure of different species of cuprous chloride from gas-phase
      electron diffraction and quantum chemical calculations.
AB  - The molecular geometry of gaseous cuprous chloride oligomers was determined by
      gas-phase electron diffraction at two different temperatures. Quantum chemical
      calculations were also performed for Cu(n)Cl(n) (n=1-4) molecules. A complex
      vapor composition was found in both experiments. Molecules of Cu(3)Cl(3) and
      Cu(4)Cl(4) were present at the lower temperature (689 K), while dimeric molecules
      (Cu(2)Cl(2)) were found in addition to the trimers and tetramers at the higher
      temperature (1333 K). All Cu(n)Cl(n) species were found to have planar rings by
      both experiment and computation. The bond lengths from electron diffraction
      (r(g)) at 689 K are 2.166+/-0.008 A and 2.141+/-0.008 A and the Cu-Cl-Cu bond
      angles are 73.9+/-0.6 degrees and 88.0+/-0.6 degrees for the trimer and the
      tetramer, respectively. At 1333 K the bond lengths are 2.254+/-0.011 A, 2.180+/
      0.011 A, and 2.155+/-0.011 A, and the Cu-Cl-Cu bond angles 67.3+/-1.1 degrees,
      74.4+/-1.1 degrees, and 83.6+/-1.1 degrees for the dimer, trimer, and tetramer,
      respectively.

PMID- 12506390
TI  - Recycling of homogeneous hydrogenation catalysts by dialysis coupled catalysis.
AB  - Although transition-metal complexes are very attractive as homogeneous catalysts
      in fine chemistry, their high prices often limit their applications. A means to
      recycle those catalysts would solve this problem and would simultaneously
      facilitate the downstream purification of the product. This is now realized in a
      new concept in which homogeneous catalysis is coupled to dialysis. The advantages
      of homogeneous catalysis (off-the-shelf catalysts, high activities and
      selectivities) are thus combined with those of heterogeneous catalysis (easy
      catalyst separation from product solution, reuse of catalyst, and possibility for
      continuous operation). Since the heart of the process is the membrane, self
      prepared membranes were preferred as they allow a better control and
      understanding of the separation characteristics. Rhodamine B was used as a probe
      molecule to define the working conditions of the membrane. The concept is proven
      to work for two relevant chiral reactions: a hydrogenation with Ru-BINAP and a
      hydrogen transfer reaction with Ru-TsDPEN [BINAP=(1,1'-binaphthalene)-2,2'
      diylbis(diphenylphosphine); TsDPEN= tosyl-N,N'-diphenyl-1,2-ethanediamine].

PMID- 12506391
TI  - New mechanistic insights into the iridium-phosphanooxazoline-catalyzed
      hydrogenation of unfunctionalized olefins: a DFT and kinetic study.
AB  - The reaction mechanism of the iridium-phosphanooxazoline-catalyzed hydrogenation
      of unfunctionalized olefins has been studied by means of density functional
      theory calculations (B3LYP) and kinetic experiments. The calculations suggest
      that the reaction involves an unexpected Ir(III)-Ir(V) catalytic cycle
      facilitated by coordination of a second equivalent of dihydrogen. Thus, in the
      rate-determining migratory insertion of the substrate alkene into an iridium
      hydride bond, simultaneous oxidative addition of the bound dihydrogen occurs. The
      kinetic data shows that the reaction is first order with respect to hydrogen
      pressure. This is interpreted in terms of an endergonic coordination of this
      second equivalent of dihydrogen, although a rate-determining step, in which
      coordinated solvent is replaced by dihydrogen, could not be ruled out.
      Furthermore, the reaction was found to be zeroth order with respect to the alkene
      concentration. This correlates well with the calculated exothermicity of
      substrate coordination, and the catalyst is thus believed to coordinate an alkene
      in the resting state. On the basis of the proposed catalytic cycle, calculations
      were performed on a full-sized system with 88 atoms to assess the appropriateness
      of the model calculations. These calculations were also used to explain the
      enantioselectivity exerted by the catalyst.

PMID- 12506392
TI  - A family of low-molecular-weight hydrogelators based on L-lysine derivatives with
      a positively charged terminal group.
AB  - A family of L-lysine-based low-molecular-weight compounds with various positively
      charged terminals (pyridinium and imidazolium derivatives) was synthesized and
      its gelation behavior in water was investigated. Most of the compounds can be
      very easily synthesized in high yields (total yields >90 %), and they function as
      excellent hydrogelators that form hydrogels below 1 wt %; particularly,
      N(epsilon)-lauroyl-N(alpha)-[11-(4-tert-butylpyridinium)undecanoyl]-L-lysine
      ethyl ester (2 c) and N(epsilon)-lauroyl-N(alpha)-[11-(4
      phenylpyridinium)undecanoyl]-L-lysine ethyl ester (2 d), which are able to gel
      water at concentration of only 0.2 wt %. This corresponds to a gelator molecule
      that entraps more than 20 000 water molecules. All hydrogels are very stable and
      maintain the gel state for at least 9 months. TEM observations demonstrated that
      these hydrogelators self-assemble into a nanoscaled fibrous structure; a three
      dimensional network is then formed by the entanglement of the nanofibers. An FTIR
      study in [D(6)]DMSO/D(2)O and in CHCl(3) revealed the existence of intermolecular
      hydrogen bonding between the amide groups. This was further supported by a (1)H
      NMR study in [D(6)]DMSO/H(2)O. A luminescence study, in which ANS (1-anilino-8
      naphtharenesulfonic acid) was used as a probe, indicated that the hydrogelators
      self-assemble into nanostructures possessing hydrophobic pockets at a very low
      concentration. Consequently, it was found that the driving forces for self
      assembly into a nanofiber are hydrogel bonding and hydrophobic interactions.

PMID- 12506394
TI  - Synthesis, structural evaluation, and estrogen receptor interaction of 4,5-bis(4
      hydroxyphenyl)imidazoles.
AB  - 4,5-Bis(4-hydroxyphenyl)imidazoles with 2,2'-H (1),2,2'-F (2),2,2'-Cl (3), and
      2,2'6-Cl (4) substituents in the aromatic rings were synthesized by oxidation of
      the respective methoxy-substituted (R,S)/(S,R)-4,5-diaryl-2-imidazolines with
      MnO2 and subsequent ether cleavage with BBr3. N-alkylation of 1 and 3 with ethyl
      iodide yielded the compounds 5 and 6. The imidazoles were characterized by NMR
      spectroscopy and tested for estrogen receptor binding in a competition experiment
      with [3H]estradiol using calf uterine cytosol. Gene activation was verified in a
      luciferase assay using estrogen receptor positive MCF-7-2a cells stably
      transfected with the plasmid ERE(wtc)luc. All halide substituted imidazoles
      competed with estradiol for the binding site at the estrogen receptor. The N
      ethyl derivative 6 showed the highest relative binding affinity of 1.26 %.
      Treatment of MCF-7-2a cells, however, did not lead to gene activation. The
      relative activation of 6 amounted only to 10% at 1 microM compared to E2 (100%).

PMID- 12506395
TI  - Quantitative structure-activity relationship study of recently synthesized 1,4
      dihydropyridine calcium channel antagonists. Application of the Hansch analysis
      method.
AB  - The Hansch analysis method was applied to a series of recently synthesized
      nifedipine analogues containing nitroimidazolyl, phenylimidazolyl, and
      methylsulphonylimidazolyl groups at the C-4 position and different ester
      substituents at C-3 and C-5 positions of the dihydropyridine ring. Hydrophobic,
      electronic, inductive, and resonance substituent constants were used. The effect
      of these parameters on the biological activity of 1,4-dihydropyridines (calcium
      channel antagonist activity in Guinea-pig ileal cells, log (1/IC50)) was
      determined by multiple linear regression analysis. Linear and quadratic
      relationships were obtained between the activity and these parameters. It was
      found that both electronic and hydrophobic interactions occur between the
      nifedipine analogues and the receptor.

PMID- 12506396
TI  - Synthesis of symmetrical 1,5-bisacyloxyanthraquinone derivatives and their dual
      activity of cytotoxicity and lipid peroxidation.
AB  - Symmetrical bis-substituted anthraquinones were successfully prepared and
      demonstrated potent cytotoxicity against the growth of suspended murine and human
      tumors, i.e. rat glioma C6 cells and human hepatoma G2 cells.We report here a
      convenient synthetic pathway that leads to symmetrically substituted 1, 5
      bisacyloxyanthraquinone derivatives. Acylation of the hydroxyl group of 1, 5
      dihydroxyanthraquinone with the appropriate acyl chlorides in the presence of
      pyridine or sodium hydride, respectively, furnished this structural class of
      anthraquinones. The bis(butyryloxy) analog 2b, bis(2-chlorobenzoyl) analog 2f,
      and bisphenylpropionyloxy analog 2n exhibit potent cytotoxicity in inhibition of
      human hep G2 cell growth in culture, as determined by using XTT colorimetric
      assay, while their antiproliferative activity is markedly enhanced and is
      comparable to that of the anticancer agent mitoxantrone. In addition, redox
      properties of the compounds for the inhibition of lipid peroxidation in model
      membranes were determined. Compounds 2n also exhibited stronger antioxidant
      activity than ascorbic acid, (+)-alpha-tocopherol, and anthrarufin. Biological
      evaluation and SAR studies of these symmetrical anthraquinones have been
      performed and the results are discussed.

PMID- 12506397
TI  - 7-Substituted-[1,4]dioxano[2,3-g]quinazolines as inhibitors of epidermal growth
      factor receptor kinase.
AB  - With the aim of developing inhibitors of EGFR tyrosine kinase, the 7
      methoxymethyl-[1,4]dioxano[2,3-g]quinazolines (3a-b) and 7-mono- or di
      alkylaminomethyl-[1,4]dioxano[2,3-g]quinazolines (4a-i) were prepared and
      evaluated for the inhibition of EGFR tyrosine kinase and the growth inhibition of
      human tumor cell lines. Among them, compounds 4d and 4h showed potencies against
      both EGFR tyrosine and the A431 cell line similar to that of PD153035 with
      greater aqueous solubilities of their HCl salts.

PMID- 12506398
TI  - Synthesis and in vitro antimicrobial evaluation of 5-(1-methyl-5-nitro-2
      imidazolyl)-4H-1,2,4-triazoles.
AB  - The increasing clinical importance of drug-resistant pathogens has lent
      additional urgency to antimicrobial research. Various 5-(1-methyl-5-nitro-2
      imidazolyl)-4H-1,2,4-triazoles (4a-6f) were synthesized and tested in vitro for
      their antibacterial and antifungal activities. Compounds 4a and 4b exhibited
      significant effects against Bacillus subtilis at MIC ranges of 0.5-1 microg/mL
      and moderate effects against Staphylococcus aureus.

PMID- 12506399
TI  - Cyclin A2 is differentially expressed during oocyte maturation between
      gynogenetic silver crucian carp and gonochoristic color crucian carp.
AB  - Silver crucian carp (Carassius auratus gibelio) is a unique gynogenetic fish.
      Because of its specific genetic background and reproduction mode, it is an
      intriguing model system for understanding regulatory mechanism of oocyte
      maturation division. It keeps its chromosomal integrity by inhibiting the first
      meiotic division (no extrusion of the first pole body). The spindle behavior
      during oocyte maturation is significantly different from that in gonochoristic
      fish. The chromosomes are first arranged in a tripolar spindle, and then they
      turn around and are reunited mutually to form a normal bipolar spindle. A new
      member of the fish A-type cyclin gene, cyclin A2, has been isolated by
      suppression of subtractive hybridization on the basis of its differential
      transcription in fully-grown oocytes between the gynogenetic silver crucian carp
      and gonochoristic color crucian carp. There are 18 differing amino acids in the
      total 428 residues of cyclin A2 between the two forms of crucian carps. In
      addition, cDNAs of cyclin Al and cyclin B have also been cloned from them. Thus
      two members of A-type cyclins, cyclin Al and cyclin A2, are demonstrated to exist
      in fish, just as in frog, humans, and mouse. Northern blotting reveals that
      cyclin A2 mRNA is more than 20-fold and cyclin A1 mRNA is about 2-fold in fully
      grown oocytes of gynogenetic silver crucian carp compared to gonochoristic color
      crucian carp. However, cyclin B does not show such a difference between them.
      Western blot analysis also shows that the cyclin A2 protein stockpiled in fully
      grown oocytes of gynogenetic crucian carp is much more abundant than in
      gonochoristic crucian carp. Moreover, two different cyclin A2 expression patterns
      during oocyte maturation have been revealed in the two closely related crucian
      carps. For color crucian carp, cyclin A2 protein is translated only after hormone
      stimulation. For silver crucian carp, cyclin A2 protein can be detected
      throughout the process of maturation division. The different expression of cyclin
      A2 may be a clue to understanding the special maturation division of gynogenetic
      silver crucian carp.

PMID- 12506400
TI  - Two morphological types of pineal window in catfish in relation to photophase and
      scotophase activity: a morphological and experimental study.
AB  - The pineal window is a transparent/translucent pineal covering on the dorsal
      surface of the cranium of certain fishes and is associated with light reactions
      of fish. In the present study, catfish species Clarias batrachus, Heteropneustes
      fossilis, Mystus vittatus, M. seenghala, and M. cavassius were examined for the
      type of pineal window present. Two morphologically different types of pineal
      window were found: an opaque-looking pineal window in C. batrachus and H.
      fossilis and a translucent type of pineal window in M. vittatus, M. seenghala,
      and M. cavassius. The distributional pattern of pigments in the melanophores at
      the pineal window were studied in terms of Melanophore Index (MI). In all of the
      species studied, a pineal foramen, a subepidermal lens-like tissue, and pineal
      end vesicle were present. Experiments were carried out on catfish having the
      opaque pineal window, as it is uncommon in catfish. Catfish with normal and
      shielded pineal window were exposed to conditions of artificial constant
      illumination (LL) and darkness (DD) to evaluate the effects of altered
      photoperiods on the state of pigmentation of melanophores at the pineal window.
      Recordings of diel activity patterns, which are light dependent in catfish, were
      carried out under both natural and artificial photoperiods in fish with a normal
      or shielded window in order to assess its functional nature. The existence of two
      morphologically and functionally different types of pineal window in a relatively
      closely related group of catfish has been demonstrated in this study. The nature
      of the opaque type of pineal window has been reconsidered based on new
      experimental evidence.

PMID- 12506401
TI  - Lactic acid is absorbed from the small intestine of sheep.
AB  - A series of experiments was conducted in vivo on anaesthetized sheep to explore
      the hypothesis that lactic acid is absorbed from the small intestine of sheep.
      Test solutions varying in lactic acid concentration, pH, osmolarity, and with
      fixed physiological concentrations of volatile fatty acids (VFAs), K+, Na+, NH4
      +, Cl-, and PO4 (-3), were separately introduced into clean, surgically sealed
      pouches. Studies were undertaken in 27 sheep, each with three pouches in the
      middle of the duodenum, jejunum, and ileum. Samples were taken at 15-minute
      intervals for 60 minutes to determine the absorption rates. The experimental
      results showed that L- and D-lactic acid were absorbed from the pouches of the
      duodenum, jejunum, and ileum throughout the 60 minutes. In the test solutions
      with pH 5.3, 420mOsmol/kg, and 12.5mM lactic acid that are in vivo conditions of
      light lactic acidosis, the mean absorption rates of D-lactic acid and L-lactic
      acid pooled from three pouches were similar, 0.07micro mol/cm2/min and 0.06micro
      mol/cm2/min, respectively, based on absorptive surface area. The mean absorption
      rates of DL-lactic acid from the duodenum, jejunum, and ileum pouches were almost
      the same, 0.14, 0.14, and 0.11micro mol/cm2/min, respectively. The absorption of
      lactic acid varied depending on lactic acid concentration, and there was a
      curvilinear relationship between lactic acid concentration and its absorption
      rate. A decrease in pH and osmotic pressure resulted in significant,
      corresponding increases in the absorption of lactic acid (P<0.0001 and P<0.05,
      respectively).

PMID- 12506402
TI  - Nitric oxide mediates metabolism as well as respiratory and cardiac responses to
      hypoxia in the snail lymnaea stagnalis.
AB  - Lymnaea stagnalis were exposed to hypoxic and chemical challenges while
      ventilation, heart rate and metabolism were monitored. Hypoxia increased
      ventilatory behavior, but this response was eliminated by immersion in 0.75 mM
      nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7 NI). 7 NI also
      suppressed ventilatory behavior under normoxia. 10.0 mM L-arginine (ARG, the NOS
      substrate) increased ventilatory behavior under normoxia, but dampened the
      hypoxic response. The heart-rate response to NOS inhibition exhibited dose
      dependent contradictory characteristics. Under both normoxia and hypoxia 0.25 mM
      7 NI increased heart rate, while 0.75 mM 7 NI suppressed it. The effect of 0.50
      mM 7 NI depended on whether normoxia or hypoxia was coincident; under normoxia
      0.50 mM 7 NI increased heart rate, while under hypoxia this concentration
      suppressed heart rate. Exposure to ARG did not elicit dose-dependent
      contradictory responses. Heart rate increased when treated with 10.0 mM ARG under
      normoxia and hypoxia, while 1.0 mM ARG increased heart rate only under hypoxia.
      Metabolic responses to NOS inhibition also exhibited dose-dependent contradictory
      changes. V.O2 decreased over 60% in response to 0.75 mM 7 NI, and baseline V.O2
      was restored when exposure ceased. In contrast, 0.25 mM 7 NI increased V.O2 10%,
      and the increase continued after exposure ceased. 0.50 mM 7 NI decreased V.O2
      40%, but V.O2 increased when exposure ceased. ARG had only the effect of
      increasing V.O2, and only at 10.0 mM concentration. Based on these results and on
      NO's known role as a neuromodulator, we conclude that the cardio-respiratory
      responses to hypoxia are, in part, mediated by NO.

PMID- 12506403
TI  - Effects of controlled pH on organic and inorganic composition in haemolymph,
      epidermal tissue and cuticle of mud crab Scylla serrata.
AB  - Analysis of organic and inorganic compounds in plasma, epidermal tissue and
      cuticle were accomplished in the intermolt (C3 stage) of crab Scylla serrata
      incubated in different pH media. Significant changes with similar trends for
      protein, carbohydrates, glycosaminoglycans (GAG), sulphur, calcium, magnesium,
      potassium, phosphorus and copper in the plasma suggested higher dissolution in an
      acidic medium while the deposition increased in alkaline medium. Similar
      decreases in protein, carbohydrate and GAG in the epidermal compartment were
      observed from pH 4 to pH 12. However, significantly higher contents of sodium,
      chloride, potassium, phosphorus, magnesium, sulphur and copper were measured at
      pH 7.5 with a symmetrical decrease profile in both acidic and alkaline media,
      resulting from synergistic effects in the osmotic regulation. Clear changes in
      calcium concentrations were observed with a sharp increase from lower contents at
      pH 7.5 to higher at pH 12. In the cuticle, the acidic condition induced a
      significant dissolution of HCl-protein, GAG, calcium and magnesium contents. On
      the other hand, the alkaline condition induced a significant decrease in
      carbohydrate, calcium, chloride, sulphur and potassium. A reduction trend is seen
      for NaOH and H(2)O-protein contents in the cuticle. These observations suggest
      that GAG and HCl-protein might constitute the most soluble fraction with high
      affinity for calcium binding and easily removed in acidic conditions.
      Additionally, it is possible to speculate that the carbohydrates associated with
      the NaOH and H(2)O-proteins may form an interface between the soluble matrix
      fraction and the chitin framework. Sulphur groups seem to present a strong
      linkage role in this interface fraction, maybe only broken by a specific enzyme
      in extreme alkaline conditions with subsequent release of significant calcium
      from the shell.

PMID- 12506404
TI  - Balancing tissue perfusion demands: cardiovascular dynamics of Cancer magister
      during exposure to low salinity and hypoxia.
AB  - Decapod crustaceans inhabit aquatic environments that are frequently subjected to
      changes in salinity and oxygen content. The physiological responses of decapod
      crustaceans to either salinity or hypoxia are well documented; however, there are
      many fewer reports on the physiological responses during exposure to these
      parameters in combination. We investigated the effects of simultaneous and
      sequential combinations of low salinity and hypoxia on the cardiovascular
      physiology of the Dungeness crab, Cancer magister. Heart rate, as well as
      haemolymph flow rates through the anterolateral, hepatic, sternal and posterior
      arteries were measured using a pulsed-Doppler flowmeter. Summation of flows
      allowed calculation of cardiac output and division of this by heart rate yielded
      stroke volume. When hypoxia and low salinity were encountered simultaneously, the
      observed changes in cardiac properties tended to be a mix of both factors.
      Hypoxia caused a bradycardia, whereas exposure to low salinity was associated
      with a tachycardia. However, the hypoxic conditions had the dominant effect on
      heart rate. Although hypoxia caused an increase in stroke volume of the heart,
      the low salinity had a more pronounced effect, causing an overall decrease in
      stroke volume. The patterns of haemolymph flow through the arterial system also
      varied when hypoxia and low salinity were offered together. The resulting
      responses were a mix of those resulting from exposure to either parameter alone.
      When low salinity and hypoxia were offered sequentially, the parameter
      experienced first tended to have the dominant effect on cardiac function and
      haemolymph flows. Low salinity exposure was associated with an increase in heart
      rate, a decrease in stroke volume and cardiac output, and a concomitant decrease
      in haemolymph flow rates. Subsequent exposure to hypoxic conditions caused a
      slight decrease in rate, but other cardiovascular variables were largely
      unaffected. In contrast, when low salinity followed acclimation to hypoxic
      conditions, apart from an increased heart rate, there were no other
      cardiovascular changes associated with the low salinity episode. The implications
      of these changes in cardiovascular dynamics are discussed in relation to
      physiological mechanisms and the ecology of decapod crustaceans, in hypoxic or
      low salinity environments.

PMID- 12506405
TI  - Effects of prenyl pyrophosphates on the binding of PKCgamma with RACK1.
AB  - Receptors for activated C kinase (RACKs) are a group of PKC binding proteins that
      have been shown to mediate isoform-selective functions of PKC and to be crucial
      in the translocation and subsequent functioning of the PKC isoenzymes on
      activation. RACK1 cDNA from the shrimp Penaeus japonicus was isolated by homology
      cloning. The hepatopancreas cDNA from this shrimp was found to encode a 318
      residue polypeptide whose predicted amino acid sequence shared 91% homology with
      human G(beta2)-like proteins. Expression of the cDNA of shrimp RACK1 in vitro
      yielded a 45-kDa polypeptide with positive reactivity toward the monoclonal
      antibodies against RACK1 of mammals. The shrimp RACK1 was biotinylated and used
      to compare the effects of geranylgeranyl pyrophosphate and farnesyl pyrophosphate
      on its binding with PKCgamma in anti-biotin-IgG precipitates. PKCgammas were
      isolated from shrimp eyes and mouse brains. Both enzyme preparations were able to
      inhibit taxol-induced tubulin polymerization. Interestingly, when either
      geranylgeranyl pyrophosphate or farnesyl pyrophosphate was reduced to the
      submicrogram level, the recruitment activity of RACK1 with purified PKCgamma was
      found to increase dramatically. The activation is especially significant for
      RACK1 and PKCgamma from different species. The observation implies that the
      deprivation of prenyl pyrophosphate might function as a signal for RACK1 to
      switch the binding from the conventional isoenzymes of PKC (cPKC) to the novel
      isoenzymes of PKC (nPKC). A hydrophobic binding pocket for geranylgeranyl
      pyrophosphate in RACK1 is further revealed via prenylation with protein
      geranylgeranyl transferase I of shrimp P. japonicus.

PMID- 12506406
TI  - Oviductal sperm storage structure and their changes during the seasonal
      (dissociated) reproductive cycle in the soft-shelled turtle Lissemys punctata
      punctata.
AB  - The oviduct of the Indian fresh water soft-shelled turtle Lissemys punctata
      punctata was examined throughout the year under light and scanning electron
      microscopes to determine the location, histomorphological characteristics, and
      function of sperm storage structure, as well as their changes at different phases
      of the seasonal reproductive cycle. Sperm storage structures in the form of
      tubules were observed in the wall of isthmus throughout the year. These tubules
      developed either by folding or fusion of the oviductal mucosal folds and were
      lined by both ciliated and nonciliated epithelial cells. The height and secretory
      activities of the epithelia were markedly high during the breeding phase (August
      to September) but low in the nonbreeding phase (October to June). A few short
      tubules lined by cuboidal epithelium appear in the wall of infundibulum only
      during the breeding phase. Following mating (May), inseminated sperm were stored
      within the tubules of isthmus up to the pre-ovulatory stage (August). Thereafter,
      sperm associated with PAS-positive materials secreted from the epithelium
      (referred to as a carrier matrix) moved forward to the infundibulum and were
      stored within the storage tubules of the infundibulum for a short time.
      Subsequently, sperm evacuated the storage tubules and entered the oviductal lumen
      to fertilize the subsequently ovulated eggs during or prior to ovulation. The
      isthmus-tubules become shorter and narrower in the regressive phase (October to
      November) and remained so until the early preparatory phase (April). Sperm
      release might have been stimulated by estrogen secreted from the ovarian
      follicles of pre-ovulatory turtles. Stored sperm not utilized for fertilization
      remained viable not less than six months in the present turtle species.

PMID- 12506407
TI  - Monoclonal antibody G3 epitope location on Guinea pig sperm membrane protein,
      sperad.
AB  - A protein isolated from guinea pig testes was purified, characterized as having a
      molecular weight of 34 kDa, and subjected to amino acid sequencing. A monoclonal
      antibody to the protein (G11) was found to cross-react with a second monoclonal
      antibody (G3). Two peptide sequences derived from the purified protein, labeled
      as 34 kDa G11, show sequence homology with sperad. Sperad is a transmembrane
      protein present in the peri-acrosomal plasma membrane of guinea pig spermatozoa.
      Both G11 and G3 monoclonal antibodies recognise antigens on the equatorial
      segment plasma membrane of guinea pig spermatozoa following the acrosome
      reaction. Therefore, experiments were designed to check whether monoclonal
      antibody G3 epitope is present on the sperad. The intra-cytoplasmic domain and
      the extra-cytoplasmic domain of sperad was amplified from a guinea pig testes
      cDNA expression library by polymerase chain reaction and cloned into pGEM T-Easy
      vector. The recombinant pGEM T-Easy plasmids were subjected to in vitro
      transcription and translation by rabbit reticulocyte lysate system. The resulting
      translated products were immunoprecipitated with monoclonal antibody G3. The
      results obtained from this study confirmed that monoclonal antibody G3 epitope is
      located on the extra-cytoplasmic domain but not on the intra-cytoplasmic domain
      of sperad.

PMID- 12506408
TI  - Paracrine interactions of mammalian adipose tissue.
AB  - Adipose tissue develops in and/or around most lymphoid tissues in mammals and
      birds. Early reports of this widespread association and hypotheses for its
      functional basis were long ignored in the planning of in vitro studies and the
      interpretation of in vivo results. Biochemical studies on rodent tissues reveal
      many site-specific properties of adipocytes anatomically associated with lymph
      nodes and omental milky spots that equip them to interact locally with lymphoid
      cells. The paracrine interactions are strongest for the most readily activated
      lymph nodes and are modulated by dietary lipids. Perinodal adipocytes contribute
      less than those in the large nodeless depots to whole-body lipid supplies during
      fasting. Observations on wild animals show that perinodal adipose tissue is
      selectively conserved even in starvation but does not enlarge greatly in natural
      obesity. Such paracrine provisioning of peripheral immune responses improves
      their efficiency and emancipates activated lymphocytes from competition with
      other tissues for blood-borne nutrients. The relationship is found in extant
      protherians and metatherians, so it almost certainly arose early in the evolution
      of mammals, possibly as part of the metabolic reorganisation associated with
      homeothermy, viviparity, and lactation. Prolonged disruption to paracrine
      interactions between lymphoid and adipose tissue may contribute to the HIV
      associated adipose redistribution syndrome, causing selective hypertrophy of the
      mesentery, omentum, and other adipose depots that contain much activated lymphoid
      tissue. Skeletal and cardiac muscle may also have paracrine relationships with
      anatomically associated adipose tissue, but interactions between contiguous
      tissues have not been demonstrated directly.

PMID- 12506409
TI  - Biological actions of galanin.

PMID- 12506410
TI  - Combined non-radioactive detection of peptide hormones and their mRNAs in stomach
      somatostatin cells.
AB  - Non-radioactive in situ hybridization (ISH) and immunocytochemistry (ICC) have
      been used to detect somatostatin (SS) messenger RNA (mRNA) and peptide in
      antropyloric mucosa of the stomach in the rats. We have applied a method of non
      radioactive in situ hybridization histochemistry using digoxigenin labelled
      oligonucleotide probes to detect somatostatin gene expression in the stomach. In
      prehybridization stage we used proteinase K (PK) in various concentrations (from
      1 to 10 micrograms/ml) and periods (from 10 min to 1 h) but we maintained high
      background. However it was possible to detect the somatostatin mRNAs in the
      stomach mucosa making use of either background preventing solutions during the
      prehybridization, or of levamisole (20 microliters/mg) added into the
      hybridization buffer or of pepsin. Somatostatin mRNA and peptide signals were
      scattered all through the mucosa especially localized particularly at the base of
      the pyloric glands. SS peptide shown by ICC and SS mRNA shown by ISH were
      observed in different cells.

PMID- 12506411
TI  - Mapping of cyclosporin A binding sites in cyclophilin A by using synthetic
      peptides.
AB  - In order to map cyclosporin A (CsA) binding sites of cyclophilin (CyP), we
      synthesized the complete set of overlapping 157 octapeptides corresponding to
      human CyP A using the multi-pin peptide synthesis system. The pin-coupled
      synthetic octapeptides were examined in terms of binding ability to CsA by a
      modification of the enzyme-linked immunosorbent assay. Significant binding of CsA
      was detected with 35 synthetic N alpha-acetylated octapeptides possessing the N
      terminal amino acids corresponding to the residues in positions 24-26, 42-44, 69
      73, 75, 76, 89-91, 102, 116, 124-131, 144-151 and 152 in human CyP A,
      respectively. Other eight octapeptides showed moderate CsA binding activity. The
      distinct binding of octapeptides covering the C-terminal region of the CyP A was
      particularly significant. These data are to be compared with the information
      provided by X-ray and NMR studies on the CsA binding sites and furnish thus a
      test of the reported method. The present study also gave added insight into the
      CsA interaction sites of CyP.

PMID- 12506412
TI  - Molecular forms of rat angiotensinogen in plasma and brain: identification by
      isoelectric focusing and immunoblot analysis.
AB  - Angiotensinogen (Ao) is the glycoprotein precursor of the vasoactive peptide
      angiotensin II. While Ao is synthesized as multiple molecular forms, the
      biochemical characteristics of this protein in blood and other tissues have not
      been defined. In this study, the charge heterogeneity of Ao in rat plasma,
      cerebrospinal fluid and that secreted by astrocyte and neuronal cultures was
      examined using analytical isoelectric focusing in combination with immunoblotting
      and quantitative image analysis. Normal rat male plasma Ao separated into 9
      isoforms in the pI range 4.34-4.92 (1, 4.34; 2, 4.41; 3, 4.48; 4, 4.58; 5, 4.61;
      6, 4.66; 7, 4.68; 8, 4.81; 9, 4.92); the percentage contribution of each to total
      plasma Ao was 13, 20, 23, 18, 2, 7, 10, 5, and < 1, respectively. A similar
      isoelectric focusing pattern was observed in female rat plasma with the exception
      that the relative contribution of isoform 6 was reduced to 2% of total Ao.
      Cerebrospinal fluid Ao displayed a more diverse charge heterogeneity than plasma
      Ao, focusing over a broader pI range of 4.42-5.24. Astrocytes and neurons
      secreted Ao isoforms in the pI range 4.44-5.29 and 4.42-4.95, respectively, with
      the astrocyte cultures showing additional bands towards the cathode. It was
      concluded that rat Ao is secreted as multiple charged forms that are regulated in
      a sex- and cell-specific manner. These differences between plasma and brain Ao
      suggest a functional diversity, a view which is supported by recent evidence
      linking Ao variants to hypertension.

PMID- 12506413
TI  - Neuroendocrine peptides stimulate adenyl cyclase in normal and malignant prostate
      cells.
AB  - Elevations of intracellular cAMP in human prostate cancer cells have been shown
      to increase invasiveness and to promote neuronal differentiation. Since
      neuroendocrine peptides capable of activating adenyl cyclase are present in
      prostatic nerves and epithelial neuroendocrine cells, we investigated normal and
      malignant human prostate cells for changes in intracellular cAMP in response to
      the prostatic peptides vasoactive intestinal peptide (VIP), calcitonin (CT), and
      calcitonin gene-related peptide (CGRP). Normal prostate epithelial cells and
      LNCaP prostate cancer cells exhibited, respectively, 6- and 30-fold increases in
      intracellular cAMP in response to VIP. ALVA-31 and PPC-1 prostate cancer cells
      demonstrated 20- to 200-fold increases in cAMP in response to CGRP, while normal
      epithelial cells and LNCaP cells exhibited smaller (2- to 6-fold) responses. Only
      DU-145 cells increased cAMP substantially in response to CT. VIP receptor mRNA
      was identified by Northern blot analysis only in those cells that responded to
      VIP. CT receptor mRNA was identified only in DU-145 cells by polymerase chain
      reaction and Southern blot analysis. These results suggest that VIP and possibly
      CGRP receptors are likely to be present in both normal and malignant prostate
      cells. VIP or CGRP may regulate secretion of proteases by normal or prostate
      cancer cells and may influence epithelial cell differentiation.

PMID- 12506414
TI  - Substance P gene expression in acute experimental colitis.
AB  - We have previously shown (Gastroenterology, 101 (1991) 1211-1219), that substance
      P (SP) decreases early in the colon muscle layer after induction of colitis in
      rabbits. Since the SP content in the colonic muscle layer was unchanged by
      sensory denervation with capsaicin, we assume that SP is located predominantly in
      intrinsic neurons of the colon, and that the decrease of SP during inflammation
      reflects changes in intrinsic SP content. However, damage of SP neurons by
      inflammation would be another likely explanation for the decrease in SP content.
      The aim of this study was to determine SP gene expression in intrinsic (colonic
      muscle layer) and extrinsic (dorsal root ganglia, DRG) neurons to prove that SP
      transcription is preserved during colitis as an indicator of neuronal integrity.
      Colitis was induced in adult white New Zealand rabbits by formalin enemas (4 ml
      of 0.4% formalin) followed by 0.85 ml immune complex i.v. 2 h later. The animals
      were sacrificed 48 h after induction of colitis, and SP content and gene
      expression were determined by radioimmunoassay (RIA) and Northern blot analysis,
      respectively. Immunoreactive SP was reduced by 40% in the colon muscle layer and
      by 60% in the dorsal root ganglia (L4-S4) in the animals with colitis compared to
      controls without colitis. In contrast to the protein data, SP gene expression was
      not significantly altered in the colon muscle layer and the dorsal root ganglia
      48 h after induction of inflammation compared to the control tissue. The
      preserved SP gene expression suggests that the intrinsic and extrinsic SP neurons
      are viable in this inflammatory model. The decreases of immunoreactive SP in the
      colonic extracts and the DRG after induction of colitis suggest that SP is
      released from extrinsic and intrinsic neurons during inflammation.

PMID- 12506415
TI  - Melanocortins and opioids modulate early postnatal growth in rats.
AB  - This study was undertaken to investigate the effects of melanocortins and opioids
      on rat early postnatal body and organ growth. Among melanocortins tested
      desacetyl-alpha-melanocyte-stimulating hormone (alpha-MSH) at dosages of 0.3 and
      3 micrograms/g/day was effective in stimulating neonatal growth with a weight
      gain of 7 and 5.6%, respectively, after 2 weeks of treatment. Likewise, a weight
      rise of 4.2 and 3% was obtained with 3 micrograms/g/day of both alpha-MSH and
      Nle4-D-Phe7 alpha-MSH. As far as opioids were concerned, while N-acetyl-beta
      endorphin (beta-End) was ineffective, the activity of beta-End was dependent on
      dosage. Indeed, newborns treated with 0.03 microgram/g/day showed a slight, but
      significant, increase in weight, whereas a marked decrease in growth followed
      treatment with 0.3 and, mainly, 3 micrograms/g/day, with a final weight loss of
      3.4 and 5.5%, respectively. All melanocortins exerted a positive action on
      muscular and brain trophism and, in addition, desacetyl-alpha-MSH also induced a
      rise of fat deposits. On the contrary, while the 0.03 microgram/g/day beta-End
      dose caused an increase in muscular and brain weight, the higher dosages of the
      opioid were detrimental, not only for muscle and brain, but also for both liver
      and spleen weight. A slight, although significant (P < 0.05), enhancement of
      serum dehydroepiandrosterone sulfate (DHEAS) level was found after the injection
      of 0.3 microgram/g desacetyl-alpha-MSH, whereas both the 0.3 and 3 micrograms/g
      doses of desacetyl-alpha-MSH and the 3 micrograms/g dose of alpha-MSH determined
      the rise of plasma androstenedione (P < 0.05). All tested melanocortins and
      opioids failed to modify the concentrations of corticosterone. Our results
      suggest that melanocortins and opioids can modulate early postnatal growth in
      rats either by direct or indirect mechanisms.

PMID- 12506416
TI  - Endocrine cells with gastrin/cholecystokinin-like immunoreactivity in the
      pancreas of the spiny dogfish, Squalus acanthias.
AB  - Endocrine cells containing gastrin/cholecystokinin (CCK)-like immunoreactivity
      were localized to the islet tissue in the pancreas of the spiny dogfish. Most of
      these cells were located in the 'intestinal' lobe of the pancreas; only
      occasional cells were observed in the 'splenic' lobe. The gastrin/CCK-like
      immunoreactive cells were often co-localized with the 'classical' pancreas
      hormones (insulin, glucagon and somatostatin). Radioimmunoassay of water extracts
      with a C-terminally directed antiserum revealed high levels of immunoreactive
      material in the intestinal part (48.6 +/- 19.9 pmol/g) and lower levels (4.5 +/-
      0.6 pmol/g) in the splenic part. Acetic acid extracts of the intestinal lobe
      contained low levels (6.8 +/- 3.3 pmol/g) of gastrin/CCK-like immunoreactivity,
      whereas corresponding extracts of the splenic part showed no immunoreactivity.
      When the extracts were subjected to DEAE ion-exchange chromatography the
      gastrin/CCK-like peptides eluted as a major peak. After Sephadex gel filtration,
      pooled immunoreactive material from the main DEAE chromatographic peak eluted at
      a position close to that of CCK4. Further characterization by ion-exchange and
      reversed-phase HPLC showed that, in general, the immunoreactive material behaved
      like the shorter forms of the gastrin/CCK family (CCK4/G5 and CCK8/Cae 3-10).

PMID- 12506417
TI  - Cerebrospinal fluid beta-endorphin in models of hyperalgesia in the rat.
AB  - Cerebrospinal fluid (CSF) obtained by acute percutaneous puncture of the
      cisternal membrane of the halothane anesthetized rat has low but measurable
      concentrations of beta-endorphin-like immunoreactivity (beta-EPir: 32.8 +/- 3.0
      pmol/l). Chromatographic separation of beta-EPir showed that authentic beta
      endorphin1-31 was the main component of beta-EPir in cisternal CSF. Subcutaneous
      injection of 5% formalin in the hind paws did not increase beta-EPir in cisternal
      CSF. Rats with tactile paw hyperalgesia evoked by unilateral ligation of the L5/6
      nerve roots 2 weeks earlier had beta-EPir concentrations that did not differ from
      sham operated or unoperated control animals. In contrast, capsaicin injected in
      the hindpaws increased the mean beta-EPir concentration compared to saline
      injections (P = 0.006) 45 min after emerging from anesthesia following injection.
      These results show that acute activation of C fibers (by capsaicin) will evoke
      the release of beta-endorphin into the CSF, suggesting activation of the beta
      endorphin terminal systems in the brain/midbrain. The failure of formalin
      injections to release beta-EPir to CSF may be due to specificity of the afferent
      stimulus evoking beta-EPir release, a lower stimulus intensity, and/or the
      duration of the stimulus generated by formalin. The normal concentrations of beta
      EPir found in the hyperalgesic state following nerve injury suggest that the
      supraspinal beta-endorphin system does not display tonic changes under such
      conditions.

PMID- 12506418
TI  - The in vitro and in vivo resistance of synthetic enkephalin analogs to three
      enkephalin-hydrolyzing enzymes.
AB  - The magnitude of the in vitro and in vivo resistance of 3 synthetic enkephalin
      analogs, [D-Ala2,Met5]-enkephalin (DAME), [D-Ala2,Met5]-enkephalinamide (DAME
      NH2) and [D-Ala2,D-Met5]enkephalin (DADME), to 3 enkephalin-hydrolyzing enzymes,
      amastatin-sensitive aminopeptidase (AsA), phosphoramidon-sensitive endopeptidase
      24.11 (PsE) and captopril-sensitive dipeptidyl carboxypeptidase I (CsD), was
      estimated by comparing the potency of enkephalins in the absence of the peptidase
      inhibitor (PI) with that in the presence of the PI. The enhancement of the
      potency of enkephalins in the isolated mouse vas deferens preparation by 3 PIs,
      amastatin, phosphoramidon, and captopril, indicated that the resistance of
      enkephalins to AsA, PsE, or CsD was DADME [symbol: see text] DAME-NH2 [symbol:
      see text] DAME > [Met5]-enkephalin (ME), DADME > DAME-NH2 > DAME [symbol: see
      text] ME, or DADME [symbol: see text] DAME-NH2 > DAME > ME, respectively.
      Additionally, the data obtained by the s.c. administration of enkephalin analogs
      to 10-day-old rats with or without PI, showed that PsE played the most important
      role in the inactivation of both DAME and DAME-NH2. In addition to PsE, both AsA
      and CsD, or AsA alone, played the significant role in the inactivation of DAME,
      or DAME-NH2, respectively. In the inactivation of DADME, AsA alone played the
      significant role. These results showed that the 3 peptidases all played important
      roles in the inactivation of enkephalins, and therefore only an analog like
      DADME, which was quite resistant to the 3 enzymes, was able to produce the effect
      without PIs after its systemic administration. Since even DADME was not
      completely resistant to the 3 enzymes; however, its potency was further increased
      by pretreatment of infant rats with the PIs.

PMID- 12506419
TI  - The effect of body weight on the calcitonin gene-related peptide-induced
      relaxation of guinea pig gallbladder strips.
AB  - Calcitonin gene-related peptide (CGRP) has been reported to relax, in a
      concentration-dependent manner, cholecystokinin-induced tension in guinea pig
      gallbladder strips. It is now shown that this CGRP-induced relaxation is body
      weight dependent with the degree of relaxation inversely related to weight.
      Radioimmunoassay demonstrated that the amount of CGRP in the gallbladder
      increased with body weight. Receptor binding showed that the number of binding
      sites and the affinity of the receptor decreased with increasing body weight.
      CGRP may play a role in the normal pattern of gallbladder contraction and
      relaxation. Decreased motility, even between periods of complete emptying, has
      been demonstrated to have a role in gallbladder diseases. The decreased
      sensitivity of the gallbladder to CGRP may explain the increase in abnormalities
      with age.

PMID- 12506420
TI  - Mechanisms of proton-induced stimulation of CGRP release from rat antrum.
AB  - Mechanisms of acid-evoked CGRP release from gastric afferent nerves were
      investigated in rat antral mucosal/submucosal tissues. Low pH (pH 4.0, 5.0 and
      6.0) stimulated antral CGRP release significantly and dose-dependently from rat
      antral fragments. Removal of extracellular calcium from the incubation medium
      resulted in significant inhibition (59%, P < 0.001) of acid (pH 4.0)-stimulated
      CGRP release. Conotoxin (1 x 10(-7) M), the selective blocker of N-type calcium
      channels, also significantly inhibited proton (pH 4.0)-induced CGRP release to
      values that were 74% below net stimulated levels. Neither nifedipine (1 x 10(-6)
      M), the L-type Ca(2+)-channel antagonist, nor indomethacin (1 x 10(-5) M),
      inhibitor of prostaglandin synthesis, altered acid-induced CGRP release. In
      contrast, ruthenium red (1 x 10(-5) M), capsaicin antagonist, almost completely
      prevented acid (pH 4.0)-stimulated CGRP release. Capsazepine (1 x 10(-4) M), a
      specific capsaicin receptor antagonist, also completely abolished acid-induced
      CGRP release. In conclusion, the results of these studies indicate that hydrogen
      ions are capable of evoking CGRP release from peripheral sensory neurons in rat
      antral mucosal/submucosal tissues. Proton-evoked CGRP release requires
      extracellular calcium and involves N-type calcium channels. Furthermore, acid
      appears to exert a capsaicin-like effect to evoke sensory neuropeptide release
      that is sensitive to capsazepine and ruthenium red. These data suggest that
      proton-induced antral CGRP release represents a direct action of hydrogen ions on
      mucosal/submucosal sensory dendritic nerve endings to effect local release of
      neuropeptide.

PMID- 12506421
TI  - alpha-Fluoromethylhistidine influences somatostatin content, binding and
      inhibition of adenylyl cyclase activity in the rat frontoparietal cortex.
AB  - Slow-wave sleep, wakefulness, locomotor activity and learning and memory are
      regulated in similar ways by somatostatin (SS) and histamine. To clarify the
      possible role of endogenous histamine on the somatostatinergic system of the rat
      frontoparietal cortex, we studied the effect of 50 micrograms of alpha
      fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine
      decarboxylase, administered intracerebroventricularly (i.c.v.) at 1, 4 and 6 h,
      on somatostatin-like immunoreactivity (SSLI) content and the SS receptor/effector
      system. The histamine content in the frontoparietal cortex decreased to about 67,
      60 and 72% of control values at 1, 4 and 6 h after alpha-FMH administration,
      respectively. At 6 h after alpha-FMH injection, there was an increase in SSLI
      content and a decrease in the number of SS receptors, with no change in the
      apparent affinity. No significant differences were seen for the basal and
      forskolin (FK)-stimulated adenylyl cyclase (AC) activities in the frontoparietal
      cortex of alpha-FMH-treated rats when compared to the control group at all times
      studied. At 6 h after alpha-FMH administration, however, the capacity of SS to
      inhibit basal and FK-stimulated AC activity in the frontoparietal cortex was
      significantly lower than in the control group. The ability of the stable GTP
      analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC
      activity in frontoparietal cortex membranes was the same in the alpha-FMH-treated
      (6 h) and control animals. Therefore, the decreased SS-mediated inhibition of AC
      activity observed in the alpha-FMH-treated rats is not due to an alteration at
      the guanine nucleotide-binding inhibitory protein (Gi) level but rather may be
      due to the decrease in the number of SS receptors. Taken together, these data
      suggest that alpha-FMH influences the sensitivity to SS in the rat frontoparietal
      cortex.

PMID- 12506422
TI  - Pituitary adenylate cyclase activating polypeptide is expressed in autonomic
      neurons.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel vasoactive
      intestinal peptide (VIP)-like peptide, which is present in neuronal elements of
      several peripheral organs, and thus a putative neurotransmitter/modulator. In the
      present study, the expression of PACAP in two parasympathetic ganglia (otic,
      sphenopalatine) and one mixed parasympathetic/sensory ganglion (jugular-nodose)
      in rat was characterized by use of in situ hybridization and immunocytochemistry
      and compared to that of VIP and calcitonin gene-related peptide (CGRP). PACAP and
      VIP were expressed in virtually all nerve cell bodies in the otic and
      sphenopalatine ganglia; PACAP and VIP were also expressed in subpopulations of
      nerve cell bodies in the jugular-nodose ganglion. CGRP was expressed in numerous
      nerve cell bodies in the jugular-nodose ganglion and in a few, scattered, nerve
      cell bodies in the sphenopalatine ganglion. In the otic and sphenopalatine
      ganglia, PACAP- and VIP-like immunoreactivities were frequently co-localized; in
      the jugular-nodose ganglion, PACAP-like immunoreactivity was frequently co
      localized with CGRP-like immunoreactivity in presumably sensory neurons and to a
      lesser extent with VIP in parasympathetic neurons. Thus, PACAP is synthesized and
      stored in autonomic parasympathetic neurons as well as in vagal sensory neurons,
      which provides an anatomical basis for the diverse effects of PACAP previously
      described.

PMID- 12506423
TI  - New light on medicine.

PMID- 12506424
TI  - The Nanodrive Project. Inventing a nanotechnology device for mass production and
      consumer use is trickier than it sounds.

PMID- 12506425
TI  - An ancestor to call our own.

PMID- 12506427
TI  - Earthquake conversations.

PMID- 12506428
TI  - The science of bubbly. Scientists study the nose-tickling effervescence of
      champagne--an alluring and unmistakable aspect of its appeal.

PMID- 12506426
TI  - Rebuilding the food pyramid.

PMID- 12506429
TI  - Medicare and Medicaid funding issues gain momentum in final weeks of 2002
      session.

PMID- 12506430
TI  - Keeping prescription drugs affordable.

PMID- 12506431
TI  - Preventing falls and fractures.

PMID- 12506432
TI  - Physician leaders speak out.

PMID- 12506433
TI  - The road back to capitation?

PMID- 12506434
TI  - Needed: options, not mandates.

PMID- 12506435
TI  - The best investment.

PMID- 12506436
TI  - Hooked on the executive leadership program.

PMID- 12506437
TI  - Bridging the gender chasm in clinical care.

PMID- 12506438
TI  - Prescription drug formularies: ensuring access to safe and effective medications.

PMID- 12506439
TI  - Internet streamlines emergency response.

PMID- 12506440
TI  - Successful computerized physician order entry system implementation. Tools to
      support physician-driven design and adoption.

PMID- 12506441
TI  - New performance model helps transform Veterans Health agency.

PMID- 12506442
TI  - New application tracks nursing care, results.
AB  - More accurate information available both for self-evaluation and benchmarking.
      Outcome performance improvement can be tracked over time. Web-based version is
      under development.

PMID- 12506443
TI  - Hospital building design boosts patient safety.
AB  - Learning lab leads to pre-construction design process and guiding principles.
      Safety improvements are designed into new hospital building. The way a building
      functions can affect changes in organizational culture.

PMID- 12506444
TI  - Physicians help achieve quality diabetes care.
AB  - Participants show superior results in reducing diabetes risk factors. Cosponsors
      indicate level of evidence that exists for clinical guidelines. Differences
      between measures and guidelines must be clearly understood.

PMID- 12506445
TI  - Benchmarking process: select targets for change.
AB  - Previously uncollected data will be used to fuel ongoing improvement. Aggregate
      data will be shared with all 239 participating facilities. Member survey
      identifies most beneficial areas to target.

PMID- 12506446
TI  - The epigenesis of stuttering.
AB  - This paper examines the data on which the Demands and Capacities Model (DCM) is
      based with the purpose of identifying areas where future research might determine
      consilience among genetic influences at the physiological, behavioral, and
      cultural levels. The determination of consilience across different levels would
      tend to validate the genetic influence on stuttering, but more importantly it
      would also sharpen the focus of researchers interested in the various possible
      expressions that genetic influences might have and the way in which they
      influence the development of the disorder. EDUCATIONAL OBJECTIVES: The reader
      will (1) learn about the distinction, as outlined in the DCM, between
      environmental/contextual influences on stuttering development and
      intrinsic/genetic influences on stuttering development; (2) learn about the
      concept of consilience and its usefulness in conferring validity on parallel
      constructs at the physiological, behavioral, and cultural levels of stuttering
      theory; and (3) be able to identify potential areas for research that might help
      in refining our understanding of the genetic influences on stuttering
      development.

PMID- 12506447
TI  - Measuring lexical diversity in children who stutter: application of vocd.
AB  - There is growing but equivocal evidence that the language abilities of young
      children who stutter (CWS) may be depressed when compared to those of their
      fluent peers. In particular, the lexical skills of CWS have variously been
      reported to be weaker or stronger than comparison children in a number of recent
      studies. One source for such disagreement may be the measures used to compute
      lexical characteristics of these children's spoken conversations. In this study,
      we examined the concurrent validity of two measures of lexical diversity in
      spontaneous language samples, Type-Token Ratio (TTR) and the newly developed
      utility vocd (Malvern & Richards, 1997), using a standard test of expressive
      vocabulary as the comparison measure. Findings indicated that vocd values ("D")
      correlated well with standardized measures of expressive vocabulary, while TTR
      values did not. In addition, both the standardized measure and vocd revealed
      significantly poorer expressive lexical skills of CWS, whereas TTR analyses did
      not evidence this difference. Results are discussed in relation to the relative
      strength of vocd over TTR as a method for describing lexical characteristics of
      the spontaneous language samples of this population. EDUCATIONAL OBJECTIVES: The
      reader will learn about and be able to (1) identify several common measures of
      conversational vocabulary and the strengths and weaknesses of each, and (2)
      compare the performance of the young CWS in this study to their normally fluent
      peers in terms of vocabulary performance on both formal and conversational
      measures of vocabulary.

PMID- 12506448
TI  - The duration component of the stress effect in stuttering.
AB  - The purpose of the present study was to investigate whether there is a
      relationship between stuttering on stressed syllables and the duration of these
      syllables. Sixteen adults who stutter read a text consisting of 226 syllables.
      The relative stress of each syllable was rated, and syllables were categorized
      into long- and short-stressed syllables, unstressed syllables and intermediate
      syllables lying in-between. In order to isolate effects caused by within-word
      position from those caused by linguistic stress, syllables in initial and in
      subsequent positions were analyzed separately. In both word position categories
      stressed syllables were stuttered more often than unstressed syllables.
      Stuttering frequency of intermediate syllables seems to be in-between stressed
      and unstressed syllables, just as their stress level is rated in-between. Results
      regarding the duration of stressed syllables do not allow final conclusions.
      EDUCATIONAL OBJECTIVES: The reader will learn about and be able to describe (1)
      language factors related with stuttering events, (2) the stress effect in adults
      who stutter, and (3) methods to control for its confounding variables.

PMID- 12506449
TI  - Stuttering and social anxiety.
AB  - The aim of the present study was to investigate the presence of social anxiety in
      adults who stutter. This was done by administering the Inventory of Interpersonal
      Situations (IIS) (Van Dam-Baggen & Kraaimaat, 1999), a social anxiety inventory,
      to a group of 89 people who stuttered and 131 people who did not stutter. Two
      components of social anxiety were measured by the ISS, the extent to which
      emotional tension or discomfort is perceived in social situations and the
      frequency with which social responses are executed. The people who stuttered
      displayed significantly higher levels of emotional tension or discomfort in
      social situations. They also reported a significantly lower frequency of social
      responses compared to their nonstuttering peers. In addition, about 50% of the
      scores of the people who stuttered fell within the range of a group of highly
      socially anxious psychiatric patients. The results of the study suggest that the
      measurement of social anxiety is an important element in the assessment of adults
      who stutter. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to
      describe (1) the IIS as an assessment procedure for evaluating social anxiety,
      (2) the level of discomfort expressed by adult stutterers in social situations,
      and (3) the effect of social anxiety on stutterers' responsiveness in social
      situations.

PMID- 12506450
TI  - Communicating in the real world: accounts from people who stammer.
AB  - This qualitative study used in-depth interviews to explore the communicative
      experiences and coping strategies of 14 adults who stammer. Their accounts
      revealed that those participants with persistent developmental dysfluency felt
      that stammering had limited their lives especially in the areas of employment,
      education and self-esteem. All participants shared key styles of communicative
      management with avoidance and confrontation developing during childhood. The
      participants who had undertaken therapy during adulthood, relied upon a range of
      speech management techniques including self-evolved and therapeutic strategies.
      Many of the strategies regularly used by the respondents contributed to the
      limiting experience of stammering. This study highlights the experience of
      stammering on the individual, discusses the variety of strategies used to manage
      dysfluency and indicates the complexities of day-to-day communication. These
      findings are discussed in relation to speech and language therapy for adults who
      stammer. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to give
      examples of: (1) the lived experience of stammering; (2) the communicative
      strategies used by adults; and (3) the situational management of stammering.

PMID- 12506451
TI  - ORYX data transmission requirement suspended for behavioral health care, home
      care, and long term care.

PMID- 12506452
TI  - Accreditation Committee keeps tabs on important accreditation issues.

PMID- 12506453
TI  - Improving your organ donation program--Part II.

PMID- 12506454
TI  - Scoring of new and revised long term care standards.

PMID- 12506455
TI  - DM program focuses attention on complex, high-cost patients.

PMID- 12506456
TI  - Drug companies offer DM programs for MS patients.
AB  - Though many providers and DM vendors have scoffed at pharmaceutical company
      sponsored DM as little more than product marketing, many of these programs go way
      beyond that to offer real clinical value to patients. Several drug companies that
      offer crucial therapies for MS patients provide a perfect case in point.

PMID- 12506457
TI  - Unique collaborative tackles poor birth outcomes.
AB  - Decades of well-meaning efforts have shown that boosting birth outcomes is not
      easy--particularly in Medicaid populations. That's why the Medicaid/managed care
      plans in southeastern Pennsylvania decided to work together toward that goal,
      along with a pioneering organization that is taking charge of collecting and
      tracking data. Now five years into this unique collaboration, HEDIS scores are
      rising and participants anticipate that improved outcomes are on the way

PMID- 12506458
TI  - Modest interventions deliver significant results in cholesterol management.
AB  - Countless studies have proven the value of lipid-lowering therapy in managing
      cholesterol levels, but for a variety for reasons, under-treatment of
      hyperlipidemia is widespread--even among patients who have already suffered from
      at least one adverse cardiac event. Fortunately, however, the problem may not be
      that difficult to fix. New research suggests that even modest DM interventions
      can have a big impact on outcomes and downstream costs.

PMID- 12506459
TI  - Perspectives. MedPAC: cost-sharing changes could boost Medicare efficiency.

PMID- 12506460
TI  - Perspectives. Hospital costs contribute to double-digit 2003 premium hikes.

PMID- 12506461
TI  - Perspectives. Advocates seek to weld family caregivers into political force.

PMID- 12506462
TI  - Perspectives. Medicaid is vital ... and hostage to demography, economic trends.

PMID- 12506463
TI  - Perspectives. Uninsured people get less care, worse care.

PMID- 12506464
TI  - Perspectives. 'Uninsured' is dangerous to your health, studies conclude.

PMID- 12506465
TI  - Perspectives. For once, bipartisan accord: Bush credit is too small.

PMID- 12506466
TI  - [Genomic alterations in preneoplastic lesions].
AB  - The genomic alterations in preneoplastic lesions are summarized in this review.
      3p and 9p in the lung, 9p in the bladder, 8p in the prostata, 19q and 1p in
      oligodendroglioma, and 22q in meningioma were reported to be deleted. Somatic
      mutation of p53 was found in preneoplastic lesions of the esophagus, stomach,
      colon, thyroid, and astrocytoma. Adenoma-carcinoma sequence (Apc, ras, p53 gene
      alterations) in colon, LKB1 gene in Peutz-Jeghers syndrome, Smad4 in juvenile
      polyposis, hMSH2, hMLH1, PMS1, PMS2 genes in HNPCC, VHL gene in kidney, WT1 in
      Wilms tumor, RB gene in retinoblastoma, and ret gene in MEN were reportedly
      altered in preneoplastic lesions involved in hereditary tumors. Cervical
      dysplasia and papilloma of the head and neck infected by human papilloma virus
      and liver infected by B-type hepatitis virus are also precancerous. Genomic
      instability, APC gene alteration, point mutation of K-ras in preneoplastic
      lesions of stomach and K-ras and p16 alterations in metaplasia of pancreas were
      also found. Advances in research on genomic alterations in preneoplastic lesions
      will contribute to prevention and early detection of cancer.

PMID- 12506467
TI  - [Recent advance in adjuvant therapy for breast cancer].
AB  - Adjuvant systemic therapy has contributed to a significant improvement of disease
      free and overall survival in addition to surgery and irradiation to the local
      disease. The adjuvant therapy to a patient is determined integrating the
      information on estimated risk of recurrence, benefit and harm of the therapy and
      the patient's value. In this review, the state of the art of adjuvant therapy is
      discussed from several aspects, such as interpretation and evaluation of risk,
      the best available evidences on adjuvant systemic therapy, the future direction
      of primary therapy for breast cancer, and patient-oriented decision making.

PMID- 12506468
TI  - [Postoperative adjuvant treatment for non-small cell lung cancer].
AB  - The subjects in this study were patients who received postoperative adjuvant
      treatment for non-small cell lung cancer, had pathological stages I through IIIA,
      and underwent complete resection of their tumors. Many phase III trials with
      chemotherapy, radiotherapy, chemoradiotherapy or other modalities as
      postoperative adjuvant treatment have been conducted. However, no adjuvant
      treatment has been established as a result of those trials.

PMID- 12506469
TI  - [Progress of postoperative adjuvant therapies for esophageal cancer].
AB  - Among the gastrointestinal cancers, esophageal cancer is supposed to be
      relatively sensitive to both radiotherapy and chemotherapy. The efficacy of
      combined chemo-radiotherapy in unresectable patients has been confirmed by
      several investigators. However, no prospective randomized controlled trials with
      surgery alone as a control had demonstrated significant survival benefit by
      postoperative adjuvant radiotherapy or chemotherapy in resectable patients. Only
      a slight prolongation of disease-free survival has been demonstrated with
      postoperative CDDP + 5-FU therapy. Thus, at present time, postoperative adjuvant
      therapy is not considered to be a standard therapy for resectable esophageal
      cancer. Clinical trials with more active combination chemotherapy including new
      anticancer drugs and new therapeutic strategies such as specific cancer
      immunotherapy and molecular targeting agents are hoped for in the future.

PMID- 12506470
TI  - [Progress in postoperative adjuvant chemotherapy in gastric cancer].
AB  - Clinical trials of adjuvant chemotherapy after surgery of gastric cancer have a
      long history dating since the late 1950s, but no standard regimen is yet
      established. Early studies included 5-FU- or TSPA-based regimens, sometimes
      combined with Me-CCNU or BCNU in Western countries, and resulted in a negative
      survival benefit, whereas 5-FU or MMC alone, or in combinations such as with MFC,
      were tried in Japan, and resulted in marginal survival benefit in the subset of
      moderately locally advanced diseases. Oral administration of 5-FU or its
      derivatives characterized Japanese trials in 1980s, though no definite benefit is
      yet established. Recent reports from Western countries regarding ELF, MMC + TGF,
      and FEM suggest significant or subsignificant survival benefit after curative
      gastrectomy. Meta-analysis of randomized trials also suggested marginal
      significant survival benefit, and these results encourage future trials with new
      drugs. The same regimens administered following surgery with different technical
      skill may result in different outcomes, and treatments in our country should be
      established based on our trials.

PMID- 12506471
TI  - [Progress in adjuvant therapy for colorectal cancer].
AB  - The progress and role of adjuvant therapy for resectable colorectal cancers are
      reviewed herein. 5-FU/leucovorin is considered the standard treatment in the
      postoperative adjuvant chemotherapy for Dukes'C colon cancer. The oral 5-FU
      prodrugs, such as UFT and capecitabine, will replace 5-FU infusion in the
      adjuvant chemotherapy in the near future. In Dukes'B colon cancer, the results of
      postoperative adjuvant chemotherapy are controversial. Many randomized trials in
      the USA and Europe have demonstrated that pre- or postoperative radiation therapy
      for rectal cancer decreases local recurrences but has no additional benefit on
      survival compared with 5-FU-based adjuvant chemotherapy. Adjuvant radiation
      therapy for rectal cancer is not widely used in Japan, while chemotherapy is
      considered the adjuvant treatment of choice. The local recurrences of rectal
      cancer is a surgeon-related phenomenon: the surgical technique used and the skill
      of the surgeon are major factors influencing outcome.

PMID- 12506472
TI  - [Interim report of JFMC study no. 23--phase III randomized clinical trial on the
      effectiveness of low-dose cisplatin plus 5-FU as a postoperative adjuvant
      chemotherapy for advanced gastric cancer].
AB  - The interim analysis of the JFMC study as of May, 2001 covers 190 gastrectomized
      patients with advanced gastric cancer from 82 institutions between May, 1996 and
      March, 2000. Patients were randomly assigned to the following two regimens. Group
      CD: cisplatin (CDDP) 5 mg/body/day (i.v.) plus 5-FU 300 mg/body/day (cvi) day 1
      5, given for 6 weeks, followed by UFT 200 mg (as tegafur) x 2/day for as long as
      possible. Group-UF: UFT only was administered after surgery as long as possible.
      The primary endpoint was survival and the secondary endpoint was disease-free
      survival. The 4-year survival rates were 47.6% in CD and 41.3% in UF, and the
      hazard ratio of CD versus UF was 0.74 (95% CL: 0.47-1.16, p = 0.189) according to
      a stratified (with stage) logrank analysis. The 4-year disease-free survival
      rates were 50.1% in CD and 39.3% in UF, and the hazard ratio of CD versus UF was
      0.65 (95% CL: 0.42-1.00, p = 0.049). Cox's regression analysis using time
      dependent dummy variables, revealed that the effect on the survival was
      accentuated within 9 months, that on disease-free survival within 6 months. The
      quality of life (QOL) of patients for one year after surgery in CD was
      significantly lower than that of patient in UF, as assessed using a QOL
      questionnaire. Although the present interim analysis does not statistically
      confirm the efficacy of the "low-dose CDDP plus 5-FU" regimen, an expectation for
      better results is suggested if this regimen is administered for a longer period
      of time. The JFMC Clinical Trial Committee permitted the release of this report
      on the condition that further study to verify the present study will be
      conducted.

PMID- 12506473
TI  - [Weekly administration of gemcitabine in outpatient clinic for non-small cell
      lung cancer].
AB  - We treated inoperable or recurrent non-small cell lung cancer (NSCLC) patients
      with weekly outpatient administration of gemcitabine. The aim of this therapy was
      to improve or to maintain the patients' performance status. From November 1999 to
      December 2001, 15 NSCLC patients were treated with gemcitabine. The patients were
      12 males and 3 females, 14 with adenocarcinoma and 1 with squamous cell
      carcinoma, aged 57 to 81 years old. A dose of 1,000 mg/m2 of gemcitabine was
      administered on days 1 and 8 every 3 weeks. Patients were treated for 1 to 17
      (median 3) months. Performance status was maintained in 12 of 15 patients during
      this treatment. Average tumor marker doubling time was 289 days. Median survival
      time was 8.1 months. Weekly administration of gemcitabine in an outpatient
      setting is a useful treatment for inoperable or recurrent non-small cell lung
      cancer.

PMID- 12506474
TI  - [Correlation between enzymatic activity and gene expression of orotate
      phosphoribosyl transferase (OPRT) in colorectal cancer].
AB  - BACKGROUND: Orotate phosphoribosyl transferase (OPRT) is the initial key enzyme
      in the 5-FU metabolic pathway. It is an enzyme that converts 5-fluorouracil into
      5-fluorouridine monophosphate. We have previously shown that there is a strong
      positive correlation between OPRT activity and the antitumor effects of 5-FU. In
      this study, we investigated the correlation between OPRT activity and mRNA
      expression levels of OPRT in 10 colorectal tumors. METHODS: Activity was measured
      by radioassay in tissues. mRNA expression levels (OPRT/beta-actin) were measured
      by TaqMan PCR assay in the same tissues. RESULTS: There was no correlation
      between OPRT activity and mRNA expression levels (r = -0.4301, p = 0.8926).
      DISCUSSION: The absolute amount of an enzyme is determined by speed of synthesis
      (kappa s) and degradation (kappa deg). OPRT is thought to be a constitutive
      enzyme, and the results of this study show that it is difficult to estimate the
      OPRT activity from mRNA expression levels. CONCLUSIONS: Further studies are
      necessary to develop techniques to measure OPRT activity in biopsies, in order to
      establish tailor-made therapies based on estimating the antitumor effect of 5-FU
      from OPRT, an enzyme related to 5-FU metabolism.

PMID- 12506475
TI  - [Gemcitabine in elderly patients with unresectable pancreas cancer].
AB  - The efficacy and safety of gemcitabine at a starting dose of 1,000 mg/m2
      administrated once a week for 3 weeks with 1 week's rest was investigated in
      elderly 11 patients with unresectable pancreatic cancer. Objective response was
      not documented. However, pain intensity, analgesic consumption and Karnofsky
      Performance Status (KPS) were frequently improved. In total, a clinical benefit
      was observed in 8 out of 11 (73%) patients. Toxicity was mild and well tolerated.
      These results suggest that gemcitabine had a superior clinical benefit and a mild
      toxicity profile. Gemcitabine should be the standard treatment in elderly
      patients with unresectable pancreatic cancer.

PMID- 12506476
TI  - [Modified pharmacokinetic modulation chemotherapy (PMC) with medication of UFT
      and intraarterial infusion of 5-FU for advanced unresectable HCC].
AB  - Advanced unresectable hepatocellular carcinoma (HCC) was treated with modified
      pharmacokinetic modulation chemotherapy (PMC). METHOD: Modified PMC consists of
      medication with UFT and intraarterial infusion of 5-FU. The dose of UFT is 300 or
      400 mg/day. The infusion to hepatic artery of 5-FU is performed with 500 mg/body
      in an outpatient clinic once a week from reservoir port for 5 hours. RESULTS: The
      number of recurrent cases after hepatectomy was 5, and that of initial cases with
      unresectable HCC was 3. Three cases had tumor thrombus in the main portal branch.
      One patient had tumor thrombus in the inferior vena cava, which reached to the
      right atrium. The mean number of infusions in all cases was 21. One case showed
      PR, and 3 cases NC. Three of 6 mortality cases died from liver failure without
      tumor progression. One year survival rates of the patients with tumor thrombus in
      the portal trunk or IVC were 75.0%. The mean survival period of these cases was
      12.5 +/- 4.2 months. CONCLUSION: Modified PMC had no severe side effect and was
      effective for advanced unresectable HCC.

PMID- 12506477
TI  - [A case of large carcinoma of the tongue and mouth floor, in which chemotherapy
      using a combination of nedaplatin and 5-FU was effective].
AB  - We encountered a case of extensive squamous cell carcinoma ranging from the
      tongue to the mouth floor, in which chemotherapy using a combination of
      nedaplatin and 5-FU was effective. The patient was a 46-year-old male, who
      noticed a small mass in the mouth floor in September 2000, and visited the
      department of oral and maxillofacial surgery at a hospital on October 12, 2000. A
      27 x 15 mm tumor with erosion was noted on the mouth floor, which was diagnosed
      as squamous cell carcinoma by biopsy, and the patient was referred to our
      department for treatment on November 16, 2000. Intra-oral findings included a
      healthy-colored induration with a bulge in the area ranging from the apex of the
      tongue posteriorly for 30 mm, and from the right lateral edge of the tongue to
      the left side exceeding the median area of the tongue by approximately 7 mm. MRI
      detected a tumor of approximately 2 cm in diameter in the area ranging from the
      median area of the tongue to the right ventral side of the tongue, which
      protruded on the mouth floor side. Two courses of combination chemotherapy using
      nedaplatin and 5-FU were performed. Nedaplatin (90 mg/m2, total 143 mg) and 5-FU
      (700 mg/m2, total 1,113 mg) were administered in a first course during December
      15-19, 2000, and in the same amounts in a second course during January 23-27,
      2001. Adverse effects of gastralgia and stomatitis occurred, but they gradually
      disappeared with time. The tumor with erosion in the tongue and mouth floor and
      induration disappeared 2 weeks after administration. Tongue was recovered, so
      that tongue movement was almost normal. Postoperative MR showed no abnormal
      signals in T2-weighed images, suggesting that the tumor in the right mouth floor
      had almost disappeared. External irradiation (40 Gy/20 times/28 days, 2 Gy/day,
      opposing bilateral portal irradiation) between March 13 and April 9, 2001, and
      micro-selection high dose fractionated interstitial irradiation (42 Gy/7 times/6
      days, 6 Gy/1 time) April 18-23, 2001 were performed as booster therapy.
      Outpatient observation has shown a good clinical course without recurrence.

PMID- 12506478
TI  - [Treatment of hypercalcemia of malignancy with pamidronate in a patient with
      advanced recurrent oral cancer].
AB  - Hypercalcemia of malignancy is a common problem for cancer clinicians. Treatment
      of hypercalcemia of malignancy with pamidronate in a patient with advanced
      recurrent oral cancer is reported herein. The patient was a 36-year-old man who
      had neck lymph node metastases due to recurrence of squamous cell carcinoma of
      the buccal mucosa and complained of cloudiness of consciousness due to
      hypercalcemia. The patient was administered pamidronate. A fine reduction in
      serum calcium was observed and cloudiness of consciousness was also alleviated.
      Although treatment of hypercalcemia with pamidronate is palliative, it is
      effective against the deterioration of quality of life.

PMID- 12506479
TI  - [A case of unresectable advanced gastric cancer with peritoneal dissemination
      responding to UET/low-dose CDDP combination chemotherapy].
AB  - We report the case of a 69-year-old female with unresectable gastric cancer (T3,
      N2, P3, H0, Stage IVb) accompanied by peritoneal dissemination, diagnosed on
      laparotomy. UFT/low-dose cisplatin (CDDP) combination chemotherapy was performed
      after surgery. UFT 300 mg/day was administered orally every day, and CDDP 10 mg
      was injected intravenously every week. Chemotherapy was continued for ten months
      with a total dose of CDDP of 380 mg, but was stopped after oral mucositis
      developed as a side effect. Seven months after the chemotherapy was started,
      endoscopy revealed that the gastric cancer tumors had disappeared and the gastric
      mucosa was intact. Gastric cancer recurrence occurred 2 years and 2 months after
      chemotherapy was started. Low-dose CDDP/5-FU chemotherapy and TS-1 chemotherapy
      were performed, but no effects were observed. The patient died 3 years and 6
      months after the start of initial chemotherapy, and was treated as an outpatient
      for 3 years while maintaining a good quality of life. UFT/low-dose CDDP
      combination chemotherapy offers promise as an effective tool in the clinical
      management of advanced gastric cancer with peritoneal dissemination.

PMID- 12506480
TI  - [A case of stomach cancer in which TS-1 neoadjuvant therapy was effective against
      multiple hepatic metastasis, allowing a radical cure A surgery].
AB  - It is believed that multiple hepatic metastases from stomach cancer are highly
      refractory, and resistant to clinical treatment. In the present study, TS-1
      neoadjuvant therapy administered orally in a single course brought about CR in
      the hepatic metastatic foci and PR in the primary foci, thus enabling grade A
      radical extirpation in a case of advanced stomach cancer. The patient continued
      to be treated on an ambulatory basis. His peri- and post-operative courses were
      satisfactory and the treatment was completed without the development of adverse
      effects.

PMID- 12506481
TI  - [A case of stage IV gastric carcinoma with lymph nodes metastases of the
      paraaorta responding markedly to TS-1].
AB  - A 64-year-old man had undergone subtotal gastrectomy with a D2 lymphadenectomy
      for advanced carcinoma of the stomach with paraaortic lymph nodes metastases 12
      months earlier. The histopathological findings revealed a well differentiated
      adenocarcinoma [type 2 macroscopic findings, SE, INF beta, ly2, v1, N2, M1
      (LYM)]. On admission, biochemical investigations showed an elevation of CEA, CA19
      9, and CA 125. An abdominal ultrasonography and a computed tomography (CT)
      revealed lymph node swelling of the paraaorta. After non-curative operation, he
      has received adjuvant chemotherapy with TS-1 plus CDDP. At first, 100 mg/day of
      TS-1 was orally administered for three weeks followed by two drug-free weeks,
      with CDDP (60 mg/m2/day) infused on day 8. Next, the treatment course consisted
      of four-week consecutive administration of TS-1 (80 mg/day) followed by two drug
      free weeks, with biweekly infusion of CDDP at a dose of 15 mg/m2. The CT findings
      revealed that an almost complete reduction of the metastatic paraaortic
      lymphnodes was obtained after completion of course 1, and was maintained
      thereafter. No noteworthy adverse reactions were observed and the patient has a
      good QOL. The patient is now in a good health and continues to undergo low dose
      TS-1 plus CDDP chemotherapy as an outpatient.

PMID- 12506482
TI  - [Three cases of advanced and recurrent gastric cancer treated with paclitaxel
      after TS-1 administration].
AB  - The importance of chemotherapy in the treatment of gastric cancer has increased
      after the appearance of more effective new agents such as TS-1. Therefore, the
      development of second line chemotherapy following TS-1 administration is needed
      urgently. Recently, we treated three cases of advanced and recurrent gastric
      cancers, using paclitaxel after TS-1 treatment. We herein describe these cases
      and discuss the therapeutic effect of paclitaxel and drug-related side effects in
      these patients.

PMID- 12506483
TI  - [Pancreatic islet cell carcinoma with multiple hepatic metastases successfully
      treated with a streptozocin/5-FU regimen--a case report].
AB  - A 53-year-old woman was hospitalized because of lientery and steatorrhea. CT
      scans revealed a pancreatic head tumor along with multiple liver tumors. The
      pancreatic head tumor had spread to the duodenum. Following tumor biopsy with
      gastrointestinal fiberscopy, we diagnosed a pancreatic malignant islet cell tumor
      with multiple liver metastases. Since there was no clinical evidence of
      recognized endocrinopathy, we diagnosed "nonfunctioning" tumor. At first we
      administered only 5-FU at a dose of 370 mg/m2/day continuously for two weeks.
      However, neither the pancreatic head tumor nor the metastatic liver tumors
      changed in size. We then administered streptozocin and 5-FU at doses of 1,000
      mg/m2 and 370 mg/m2, respectively, every week. The patient received a total of 10
      g/m2 of streptozocin. After this treatment, the enlarged metastatic liver tumors
      were reduced in size, with marked improvement in liver enzyme. Toxic reactions to
      this regimen were mild. Only grade 1 nausea and alopecia were observed during the
      treatment. No hematological toxicity was observed, nor, with sufficient diuresis,
      was nephrotoxicity, demonstrating that this regimen can be administered safely.

PMID- 12506484
TI  - [A case of recurrent breast cancer with carcinomatous pleurisy successfully
      treated with combined chemoendocrine-therapy of CTF (CPA, THP and 5-FU) and
      anastrozole following instillation therapy 12 years after radical mastectomy].
AB  - A 52-year-old female underwent radical mastectomy at the age of 41 for left
      breast cancer (n0, positive for ER). After a few years of adjuvant TAM therapy,
      follow-up was stopped at the age of 50 with no recurrence. She had suffered from
      symptoms of cold since January 2001 and came to our hospital complaining dyspnea
      on February 11. CXP showed pleural effusion of the entire thoracic cavity and she
      was admitted to the hospital immediately. Pleural exudate cytodiagnosis showed
      carcinomatous pleurisy; however, dyspnea and thoracic effusion were improved by
      continuous thoracic drainage and instillation therapy. Various examinations
      demonstrated that the carcinomatous pleurisy was due to recurrent breast cancer.
      They also showed local recurrence, left supraclavicular lymph node metastasis and
      multiple bone metastasis. Thus, combined chemoendocrine-therapy of CTF (CPA, THP
      and 5-FU) and anastrozole was administered. After 6 cycles of CTF, the
      carcinomatous pleurisy, local recurrence and left supraclavicular lymph node
      metastasis were diagnosed as CR by CXP, chest CT and US and multiple bone
      metastasis were diagnosed as PR by bone scintigram. The patient continues to be
      treated on an outpatient basis with no recurrence about one year after the
      beginning of the treatment (6 months after CTF 6 cycles) and she is taking
      anastrozole continuously.

PMID- 12506485
TI  - [A patient with mantle cell lymphoma who successfully underwent auto-PBSCT in
      combination with in vivo purging of tumor cells using rituximab].
AB  - The chimeric anti-CD20 monoclonal antibody rituximab was recently approved for
      the treatment of malignant B cell lymphoma. We report the case of a 49 year-old
      female with advanced mantle cell lymphoma (MCL), who successfully underwent auto
      peripheral blood stem cell transplant (auto-PBSCT) in combination with in vivo
      purging of tumor cells using rituximab. Systemic swelling was detected in her
      lymph nodes, and she was histologically diagnosed with MCL. From bone marrow
      involvement and 28% of lymphoma cells in her peripheral blood, she was identified
      as stage IV of MCL. She achieved a partial response (PR) after three cycles of
      standard chemotherapy (ProMACE-CytaBOM) followed by 1 course of rituximab at 375
      mg/m2 per week for four weeks. Prior to treatment with rituximab, IgH/bcl-1
      translocation in her peripheral blood was found to be positive in 0.5% of 199
      cells. After administration of rituximab, this fell to 0% in her peripheral blood
      and bone marrow. Stem cells were mobilized with cyclophosphamide at 2,000 mg/m2
      for 2 days, followed by granulocyte colony-stimulating factor (G-CSF). On one day
      prior to harvest, rituximab was infused at 375 mg/m2 for in vivo purging of tumor
      cells. The IgH/bcl-1 translocation in the peripheral blood stem cell harvest
      (PBSCH) product was found to be 0%. Subsequently, a pretreatment regimen of CBDCA
      at 350 mg/m2 x 4, ETP at 500 mg/m2 x 3, MCNU at 200 mg/m2 x 1, and CPA at 2,000
      mg/m2 x 2 was adopted to condition the transplant, followed by auto-PBSCT. After
      the transplant, the patient achieved an uncertain complete response (CRu). The
      present case suggests in vivo purging with rituximab is effective, and that this
      method may have a role as a first-line therapy in MCL patients who respond poorly
      to standard treatment.

PMID- 12506486
TI  - [DNA chip and SNP].
AB  - Single nucleotide polymorphism (SNP) is high-density genetic marker that could be
      utilized to dissect genetic traits that influence susceptibility to common
      diseases and responsiveness to drugs. Requirement for massive SNP analysis has
      enhanced development of various SNP genotyping technologies. DNA chip is one of
      such methods, which detects SNPs in parallel on an array of surface bound
      oligonucleotides. Recent application of DNA chip for high-throughput SNP analysis
      as well as clinical diagnosis will be presented.

PMID- 12506487
TI  - Behavior problems in demented nursing home residents: a multifaceted approach to
      assessment and management.
AB  - Behavior disturbances are common among dementia patients. Management of
      behavioral problems begins with the assessment of psychiatric, medical, and
      environmental etiologies. Treatment plans based upon behavioral or pharmacologic
      interventions can substantially reduce problematic behaviors.

PMID- 12506488
TI  - Imaging modalities in the assessment of osteoporosis.
AB  - Imaging can be helpful in the diagnosis and treatment of osteoporosis. Several
      imaging modalities have become available to assess bone mass in the peripheral,
      axial, or entire skeleton. The basic principles, indications, and limitations of
      each imaging method are presented.

PMID- 12506489
TI  - Effects of thiazolidinediones on cardiovascular risk factors.
AB  - The thiazolidinediones are the insulin sensitizers used in the management of Type
      2 diabetes mellitus. These drugs can potentially decrease the risk of
      cardiovascular disease by correcting the different components of the insulin
      resistance syndrome.

PMID- 12506490
TI  - Contemporary use of beta receptor antagonists in chronic heart failure.
AB  - beta-adrenergic receptor antagonists slow disease progression, improve symptoms,
      and increase survival. They should be considered standard of care for patients
      with stable heart failure and understanding which drugs provide benefit and how
      to initiate therapy is crucial to improving prognosis.

PMID- 12506491
TI  - A comprehensive review of physical urticaria.
AB  - Physical urticarias are an intriguing subgroup of urticarial disorders with
      unique circumstances and trigger stimuli precipitating symptom development. A
      thorough understanding of the pathophysiology will assist in the management
      process by facilitating prompt recognition and more accurate diagnoses.

PMID- 12506492
TI  - Injection and aspiration techniques for the primary care physician.
AB  - Aspiration and injection techniques are useful, relatively safe office
      procedures. The physician must have a good understanding of the basic technique
      and pertinent anatomy. The indications, contraindications and specific injection
      and aspiration techniques are discussed.

PMID- 12506493
TI  - Perioperative stroke: evaluation, management, and possible preventive measures.
AB  - Mechanisms of perioperative ischemic stroke include: hypotension,
      hypercoagulability, arrhythmias with embolism, or direct vascular insult.
      Mechanisms of perioperative hemorrhagic stroke include: use of antithrombotics,
      hypertension, or direct vascular insult.

PMID- 12506494
TI  - The acute severe headache--assessment and treatment.
AB  - Severe headache is usually primary, but secondary causes must be ruled out.
      History and physical examinations are essential. Neuroimaging, laboratory
      analysis, and imaging may also be necessary. Diagnosis and therapy for primary
      and secondary headaches are discussed.

PMID- 12506495
TI  - Latex allergy.
AB  - The prevalence of IgE mediated natural latex rubber allergy is estimated to be <
      1% in the general population, < 17% in medical personnel and approximately 0% in
      children with spina bifida. We review the definition, diagnosis, prevention, and
      treatment of NLR allergy.

PMID- 12506496
TI  - Ischaemic heart disease--more than just lipids.

PMID- 12506497
TI  - Tobacco control, the European Union and WHO. Two conventions provide
      opportunities to advance public health.

PMID- 12506498
TI  - Restrictions on import of drugs for personal use within the European single
      market.
AB  - BACKGROUND: The European Union (EU) has harmonized legislation on pharmaceutical
      products to implement the single market in this field. European consumers are
      offered with high quality and safe products that have been brought onto the
      market through harmonized procedures. The aim of the study was to find out if
      there still were legislative restrictions to purchasing prescription only
      medicines (POMs) for personal use from another EU member state. METHODS: The
      medicines authorities in the EU were inquired about the possibilities of a
      citizen to obtain POMs for personal use from another EU country. The method used
      was a questionnaire covering both the delivery of foreign prescriptions and
      import of prescription-only medicines. The questionnaire was mailed, e-mailed or
      faxed to the national medicines authorities. RESULTS: An answer was obtained from
      11 of the 15 member states. The results showed that the delivery of foreign
      prescriptions was regulated only in the Nordic countries. All the countries
      reported prohibitions on delivering prescriptions for drugs that act on the
      central nervous system and prescriptions that were suspicious. The personal
      import of drugs was restricted as to the amounts and reimbursement policy.
      CONCLUSIONS: The import of drugs for personal use is not yet comparable to other
      consumables in the EU. The prevailing restrictions contravene the community
      legislation and this problem has not yet been solved. It is probable that
      problems will arise in the near future when information technology is likely to
      be used increasingly in the delivery of drugs.

PMID- 12506499
TI  - Information from primary care: its importance and value. A comparison of
      information from Slovenia and England and Wales, viewed from the 'Health 21'
      perspective.
AB  - BACKGROUND: The WHO have set health standards in the form of 21 targets--Health
      21--and the EU are developing a set of health indicators whereby national health
      status can be measured. Data from Slovenia and from England and Wales assessing
      information systems in primary care and their capacity to deliver the
      requirements of these initiatives have been examined. In both countries, primary
      care is provided through a state-led service. METHODS: Consultation data from the
      annual report of the Department of Health Slovenia (1999) are compared in respect
      of relevant targets with data from the Fourth National Morbidity Survey (1992) in
      England and Wales. Consultation rates were standardized to the European Union 15
      country population (1998). RESULTS: Consultation rates in females were similar in
      the two countries whereas in males rates were higher in Slovenia. The
      proportionate distributions of consultations by chapter of the International
      Classification of Diseases (ICD) were similar in both countries, respiratory
      (17%) and musculoskeletal (9%) disorders ranked first and second. For eye
      diseases, injury and poisoning, factors influencing health status (e.g. medical
      examination). proportions were higher in Slovenia: for mental disorders higher in
      England and Wales. The relativity of male to female consultation rates was
      broadly similar with higher rates in females in most ICD chapters. These
      differences are considered in detail against the background of WHO targets.
      CONCLUSIONS: Data gathered systematically from the surveillance of consultations
      in primary care are important to the measurement of WHO 'Health 21' targets.

PMID- 12506500
TI  - Alcohol-related deaths contribute to socioeconomic differentials in mortality in
      Sweden.
AB  - BACKGROUND: This study aims at estimating the contribution of alcohol to
      socioeconomic mortality differentials in Sweden. METHODS: Data were obtained from
      a Census-linked Deaths Registry. Participants in the 1980 and 1990 censuses were
      included with a follow-up of mortality 1990-1995. Socioeconomic status was
      assigned from occupation in 1990 or 1980. Alcohol-related deaths were defined
      from underlying or contributory causes. Poison regressions were applied to
      compute age-adjusted mortality rate ratios for all-causes, alcohol-related and
      other causes among 30-79-year-olds. The contribution of alcohol to mortality
      differentials was calculated from absolute differences. RESULTS: Around 5%
      (9,547) of all deaths were alcohol-related (30-79 years). For both sexes, manual
      workers, lower nonmanuals, entrepreneurs and unclassifiable groups had
      significantly higher alcohol-related mortality than did upper nonmanuals. Male
      farmers had significantly lower such mortality. The contribution of alcohol to
      excess mortality over that of upper nonmanuals was greatest among middle-aged (40
      59 years) men who were manual workers or who belonged to a group of
      'unclassifiable & others' (25-35%). It was of considerable size also for middle
      aged lower nonmanuals (both sexes), male entrepreneurs, female manual workers and
      'unclassifiable & others'. Among men, the total contribution of alcohol (30-79
      years) was estimated at 16% for manual workers, 10% for lower nonmanuals and 7%
      for entrepreneurs; and among women, 6% (manual workers, lower nonmanuals) and 3%
      (entrepreneurs). CONCLUSION: Although deaths related to alcohol were probably
      underreported (e.g. accidents), alcohol clearly contributes to socioeconomic
      mortality differentials in Sweden. The size of this contribution depends strongly
      on age (peak among the middle-aged) and gender (greatest among men).

PMID- 12506501
TI  - Socio-economic position and coronary heart disease risk factors in children and
      young people. Evidence from UK epidemiological studies.
AB  - BACKGROUND: Coronary heart disease (CHD) is a condition with its origin in early
      life. In adults, CHD and its risk factors show clear socio-economic gradients.
      The aim of the present review is to collate published evidence to assess if these
      risk factor gradients are also apparent in young people in the UK. METHODS:
      Pertinent publications were identified in four ways: i) a systematic search of
      PUBMED from its inception in January 1966 until October 2000; ii) scanning the
      reference sections of identified publications; iii) searching the authors' own
      files; and iv) contacting experts in the field. RESULTS: Of eleven CHD risk
      factors, consistent evidence concerning the association in child- and early
      adulthood with socio-economic position was evident for cigarette smoking, birth
      weight, adiposity (in young adults), height, and some aspects of diet,
      particularly fat and fibre consumption. As in UK adults, the most favourable
      levels of these risk factors were seen in young people from socially advantaged
      backgrounds. For the other variables associated with CHD--physical inactivity/low
      cardiorespiratory fitness, blood pressure, blood cholesterol, adiposity (in
      children), and some emerging risk factors (C-reactive protein, homocysteine,
      fibrinogen)--there was little evidence of any clear association with socio
      economic level. CONCLUSIONS: While social variation is seen in some CHD risk
      factors in young people, further data are needed to fully explore if this is also
      the case for others. This issue could be addressed by analysing some existing but
      unutilized survey data from the UK.

PMID- 12506502
TI  - Redistributive effects of the Swedish social insurance system.
AB  - BACKGROUND: Four principles are used to distribute payments via the Swedish
      social-insurance system in cases of temporary or permanent illness and death.
      This paper studies the redistributive effects on income of these four principles.
      METHODS: The analysis is based on aggregate social-insurance data from the 25
      municipalities that comprise Stockholm County in Sweden. For nine different types
      of social-insurance payments based on the four principles, the degree of income
      redistribution is measured according to concentration indexes and differences
      between Gini coefficients with social-insurance payments excluded and included.
      RESULTS: The concentration indexes for payments from the nine social-insurance
      schemes in total is -0.0469. The Gini coefficient falls from 0.0437 excluding
      insurance payments (i.e. for income only from gainful work, IGW) to 0.0379 when
      including insurance payments with income from gainful work (IGW + TP). That is,
      the Gini coefficient is 15% lower when insurance payments are included.
      Decomposition by payment shows that the largest redistribution effect on income
      inequality is made by disability pension. CONCLUSION: Municipalities with low
      average income are favoured by the Swedish social-insurance system. Payment
      principles can be ranked according to their redistributive capacity: mix of
      compensating-lost-income and flat-rate, compensating-lost-income, means-testing,
      flat-rate, and need-based respectively. The nine social-insurance schemes
      contribute very differently to income redistribution. Disability pension and
      sickness allowance contribute most to income redistribution and reducing income
      inequality.

PMID- 12506503
TI  - 'Avoidable' mortality among immigrants in Sweden.
AB  - BACKGROUND: The concept of studying 'avoidable' mortality as an indicator of the
      outcome of health care has been applied mainly in studies of time-trends and
      geographical and socio-economic variation. METHODS: In this study, indicators of
      'avoidable' mortality among immigrants in Sweden have been studied. Comparisons
      of death rates among immigrants and those born in Sweden were made using a
      linkage of the Population Census and the Cause of Death Register, nationwide
      sources. RESULTS: For a group of health policy indicators, such as liver
      cirrhosis and malignant neoplasms of the trachea, bronchus and lung, death rates
      were about 40-100% higher among immigrants from other Nordic countries,
      Yugoslavia and Eastern Europe than among the Swedish born population. For causes
      of death considered amenable to medical care intervention there were, however,
      small differences. For some conditions, such as cerebrovascular disease,
      malignant neoplasms of colon and rectum, chronic bronchitis and emphysema, high
      death rates were found among immigrants from other Nordic countries. For
      immigrants from other countries, there were no high death rates based on medical
      care indicators when compared to the Swedish-born population. CONCLUSION: There
      were few indications of inequity reflected in the mortality outcome of medical
      care. The variation found in death rates from health policy indicators may
      reflect differences in smoking and alcohol habits.

PMID- 12506504
TI  - Ethnic differences in daily smoking in Malmo, Sweden. Varying influence of
      psychosocial and economic factors.
AB  - BACKGROUND: The aim was to investigate ethnic differences in daily smoking in
      Malmo, Sweden, and whether these differences could be explained by psychosocial
      and economic conditions. METHODS: The public health survey in Malmo 1994 is a
      cross-sectional study. A total of 5,600 individuals aged 20-80 years were
      randomly chosen to respond to a postal questionnaire. The participation rate was
      71%. The study population was divided into seven categories according to country
      of birth; Sweden, Denmark/Norway, other Western countries, former Yugoslavia,
      Poland, Arabic-speaking countries and all other countries. A multivariate
      analysis was performed using a logistic regression model in order to investigate
      the importance of possible confounders on the ethnic differences in daily
      smoking. Finally, variables measuring social network, social support and economic
      conditions were introduced. RESULTS: The prevalence of daily smoking was
      significantly higher among both men and women born in Denmark/Norway (39.1% and
      37.0%), men born in other Western countries (32.9%), Poland (34.0%) and Arabic
      speaking countries (36.4%) than among Swedish men (21.7%) and women (23.8%).
      Women born in Arabic-speaking countries had a significantly lower smoking
      prevalence (7.1%). The multivariate analysis, including age, education and snuff,
      did not affect these results. A reduction of the odds ratio of daily smoking was
      observed for men born in Arabic-speaking countries and Poland after the
      introduction of the psychosocial and economic factors in the model. Only small
      changes were observed for women. CONCLUSION: There were significant ethnic group
      differences in daily smoking. Psychosocial and economic conditions in Sweden may
      be of importance in some ethnic groups.

PMID- 12506505
TI  - Information disclosure and smoking risk perceptions. Potential short-term impact
      on Spanish students of the new European Union directive on tobacco products.
AB  - BACKGROUND: The Directive 1999/0244 (COD), recently approved by the European
      Parliament, proposed that the content and presentation of health warnings on
      cigarette packets be modified. The aim of the present study was to analyse the
      potential effect of the planned measures on the perceptions by Spanish youth of
      the risks associated with smoking. METHOD: A sample of 435 students attending the
      University of La Rioja were surveyed on their perceptions of the principal health
      risks attributable to the consumption of tobacco i.e. lung cancer, respiratory
      diseases and cardiovascular disease. A questionnaire was administered before and
      after they were presented with a demonstration of the health warnings on
      cigarette packets based on the new European Union directive. RESULTS: Perceptions
      changed significantly following exposure to the content and type of information
      of the new packaging. In general, the university students attributed a higher
      health risk to smoking following the presentation. CONCLUSIONS: The measures
      developed by the public sector to present a higher profile of anti-tobacco health
      warnings do influence the target population in the desired direction, at least in
      the short term. Hence, given that the perception of risk influences the election
      to smoke, it is predictable that when these types of policy decisions are
      applied, there will be a tendency towards a reduction in the incidence and
      prevalence of tobacco consumption.

PMID- 12506506
TI  - Cigarette smoking and stages of change among men and women in Kiev, Ukraine.
AB  - BACKGROUND: Assisting current smokers to progress towards stopping smoking
      entails identifying their readiness to stop and understanding the factors that
      may influence their readiness. Relations were established between certain
      predictor variables (intensity of smoking, age at initiation, duration of
      smoking, and gender) and stages of readiness to change smoking behaviour in Kiev,
      Ukraine. METHODS: Analysis was based on a convenient sample of 536 current
      smokers who completed a stages-of-change questionnaire in a public square in the
      centre of Kiev's business district, between 22 and 25 July 2000. Frequency
      distributions, odds ratios, the Kolmogorov-Smirnov test and the Wilcoxon rank-sum
      test were used to summarize and describe the data. Tests of significance were
      based on the 0.05 level. RESULTS: The majority of participants (56.1%) were
      categorized as precontemplative. Less than 20% of the subjects were prepared for
      action to change smoking behaviour. Later age at smoking initiation was
      associated with fewer cigarettes smoked per day. Females were more likely then
      males to seriously consider cutting down the number of cigarettes they smoked.
      However, males were more likely to have intentionally quit smoking for at least
      one day within the past year. CONCLUSION: Information on stages of readiness to
      stop smoking provided by this study may be useful for improving the effectiveness
      of smoking cessation programmes in Kiev.

PMID- 12506507
TI  - The health status of delinquent gipsy youths in Spain.

PMID- 12506508
TI  - [Clinically significant contusive heart injury: diagnostic and prognostic rules
      of screening].
AB  - For many years the definition of blunt cardiac trauma has been unclear and
      several diagnostic methods have been employed. Recently, the importance of
      detecting only those patients who have a clinically significant cardiac trauma
      has been pointed out. Electrocardiography has shown itself to be the most
      important means in order to exclude the presence of a clinically significant
      cardiac trauma in a hemodynamically stable patient, determining troponin levels
      may be helpful at least in some patients.

PMID- 12506509
TI  - [Natriuretic peptides and essential arterial hypertension].
AB  - Natriuretic peptide system plays a well-defined role in the regulation of blood
      pressure and fluid volume. Although the effects of natriuretic peptides (atrial
      natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide)
      are mediated by specific biologic receptors, their plasma level is influenced by
      clearance receptors. It has been demonstrated that in hypertensive subjects
      plasma levels of natriuretic peptides are impaired; furthermore peptide receptor
      polymorphisms have been shown to be significantly associated with hypertension
      and cardiac hypertrophy. Studying normotensive subjects at high genetic risk of
      developing hypertension on the basis of family history makes it possible to
      investigate the role of natriuretic peptide system in the genesis of
      hypertension. It has been shown that plasma atrial and ventricular natriuretic
      peptide levels are significantly reduced in normotensive subjects with a family
      history of hypertension. Our study is the first one showing association among
      positive family history of essential hypertension and natriuretic peptide
      receptor polymorphisms. We identified a novel insertion/deletion polymorphism at
      position 15,129 in the 3'-untranslated region (3'-UTR) of NPRA receptor mRNA. The
      NPRA gene deletion variant is associated with hypertensive family history and
      higher systolic blood pressure. The "deletion 15129" variant might participate in
      the functional impairment of natriuretic peptide system defining an increased
      genetic susceptibility to hypertension.

PMID- 12506510
TI  - [Transcatheter treatment of patent ductus arteriosus].
AB  - Isolated patent ductus arteriosus accounts for 10 to 18% of all cardiovascular
      malformations. Transcatheter closure of the patent ductus arteriosus has now
      become established practice with a high success rate and a low incidence of
      complications. Many devices have been proposed during the last 20 years. The use
      of some of these devices has largely been abandoned for different reasons: high
      costs, the need of large transvenous sheaths and the high incidence of late
      residual shunts. The devices currently available (Amplatzer duct occluder,
      buttoned device, DuctOcclud coil, Gianturco-Grifka vascular occlusion device,
      detachable coils) render the embolization of a patent ductus arteriosus
      relatively easy, with a short hospital stay. We feel that this is the treatment
      of choice for the majority of patients with a patent ductus arteriosus. The aim
      of this article was to review our experience and report the state-of-the-art in
      transcatheter patent ductus arteriosus therapy.

PMID- 12506511
TI  - [Home exercise therapy in chronic congestive heart failure: observational study
      of factors affecting adherence to the program].
AB  - BACKGROUND: Physical training has proven to be a valid and effective therapeutic
      tool capable of counteracting muscle changes that occur in chronic heart failure
      (CHF) patients. Nevertheless, few studies have analyzed the frequency of use of
      this therapy and the reasons for any reduced compliance and adherence to the
      prescription. The aim of this study was to quantify the frequency of the
      participation of CHF patients in a program of domiciliary physical training and
      to analyze the factors that can influence adherence to the program. METHODS:
      Three hundred and twenty-two consecutive CHF patients (ejection fraction 28 +/-
      7%) in a stable condition with optimized medical therapy performed a
      cardiopulmonary test, including determination of peak oxygen consumption, at
      baseline and after 9 +/- 3 months. All the patients had participated in sessions
      of health education on the relationship between illness/physical activity. The
      prescription of physiotherapy was decided by the physician on the basis of each
      patient's clinical need assessed in the diagnostic-therapeutic management. The
      patient referred for physiotherapy entered a therapeutic strategy that included
      sessions of training on anaerobic threshold, self-management of the session, and
      formulation of a domiciliary physical training program. During the follow-up
      evaluation the patients were asked to complete a questionnaire, which
      investigated the relationship between several factors and the patient's adherence
      to the physical training program, which was objectively evaluated by the change
      in peak oxygen consumption recorded at the end of the training, taking into
      account the spontaneous variations found in the control group. RESULTS: Two
      hundred and eighty-two of the patients (88%) satisfied the criteria for inclusion
      in the study. Only 61 (22%) of them were judged to have adhered to the
      recommended physical training. Type of employment (chi 2 = 7.08, p < 0.02), the
      state of retirement (chi 2 = 8.9, p < 0.01), ischemic etiology (chi 2 = 5.91, p <
      0.01), compatibility with employment (chi 2 = 15.8, p < 0.0004), availability of
      suitable domestic conditions (chi 2 = 14.5, p < 0.0008), the structure of the
      training program (chi 2 = 22.33, p < 0.0001) and a learning phase in a gym (chi 2
      = 71.33, p < 0.0001) were significantly correlated at univariate analysis with
      the performance of the physical training. Multivariate analysis identified the
      structure of the training program (odds ratio 9.6, 95% confidence interval 2.8
      33) and a learning phase in a gym (odds ratio 49.6, 95% confidence interval 11
      210.8) as independent factors (r2 = 0.48) determining adherence to the physical
      training program. CONCLUSIONS: Adherence to unmonitored, recommended domiciliary
      physical training appears to be modest even in patients who have been in-patients
      in a cardiac rehabilitation center. Various factors seem to influence the
      adherence of the patient to this therapy, but structural factors, such as the
      organization and learning of the program, more strongly influenced the patient's
      subsequent compliance.

PMID- 12506512
TI  - [Variations in QRS duration and axis with different sites and intervals of right
      ventricular pacing].
AB  - BACKGROUND: The aim of this study was to achieve left ventricular
      resynchronization by means of right ventricular pacing. METHODS: We studied 12
      patients (9 males, 3 females, mean age 61.7 +/- 19.5 years), with syncope, II
      degree atrioventricular block or ventricular arrhythmias, without
      intraventricular conduction disturbances. Single and dual site pacing, synchrony
      or at different delay, was made in the right ventricular, outflow tract from the
      apex, and midseptal areas. RESULTS: In all patients we obtained the shortest QRS
      duration with synchrony or delayed bisite pacing (standard ventricular apex
      pacing 170 +/- 20 ms; bisite pacing 137 +/- 13 ms). CONCLUSIONS: Our data
      demonstrate that appropriate right ventricular pacing can lead to left
      ventricular resynchronization.

PMID- 12506513
TI  - [Cardiac metastasis of poorly differentiated adenocarcinoma of unknown primary
      site].
AB  - The finding of intracardiac masses is very uncommon. In this patient the early
      clinical picture was characterized by neurologic signs and symptoms as mild
      forgetfulness, blurred vision, a sensation of imbalance, anorexia, weight loss.
      Brain magnetic resonance imaging showed multiple metastatic lesions, computed
      tomography of the chest, abdomen and pelvis showed intraatrial masses and whole
      body nuclear scanning evidenced bone lesion. It was not possible to find the
      primary tumor by other instrumental or laboratory exams. Transesophageal
      echocardiography showed a mass originating from interatrial septum, with atrial
      invasion and risk of embolization from the left atrium. The patient was
      transferred to the operating room for cardiac surgery, the mass at risk for
      embolization was resected and the specimen consisted of fibrous and fibrino
      necrotic tissue infiltrated by poorly differentiated adenocarcinoma. The patient
      received brain and bone radiotherapy and chemotherapy with cisplatin and
      vinorelbin.

PMID- 12506514
TI  - [Non-bacterial thrombotic endocarditis: a rare case of recurrent embolic events].
AB  - Non bacterial thrombotic endocarditis is a rare disease. The real incidence is
      not known and seems to range from 0.9 to 9.3%. Generally it is associated with
      cancer and rarely diagnosed antemortem. We describe the case of a female patient
      who suffered from ictus cerebri and acute myocardial infarction. She was admitted
      with diagnosis of papillary fibroelastoma arising from the right aortic leaflet.
      Her past medical history was characterized by gastrectomy, splenectomy and
      partial pancreatectomy for gastric cancer. The patient underwent successful
      resection of the mass that was attached to the right leaflet of the aortic valve
      closed to the aortic annulus. The histopathological examination revealed a mass
      composed of only thrombotic material. At the follow-up 1 year later the patient
      was in good clinical conditions (NYHA functional class I). Transthoracic
      echocardiography showed a good ventricular function, a continent aortic valve
      without recurrent mass. The suspicion of non bacterial thrombotic endocarditis
      should be aroused when diagnosis of endocardial mass is made in patients with
      previous cancers.

PMID- 12506515
TI  - [A balloon attached to a thread].

PMID- 12506516
TI  - [Acute myocardial infarction with persistent ST segment elevation: towards an
      appropriate diagnostic and therapeutic approach in the health care community].

PMID- 12506517
TI  - [Re-reading a page of Cesare Frugoni].

PMID- 12506518
TI  - Is the chest pain in cardiac syndrome X due to subendocardial ischaemia?

PMID- 12506519
TI  - Role of CagA positive Helicobacter pylori strains in ischemic heart disease and
      in ischemic stroke.

PMID- 12506520
TI  - The role of dobutamine stress echocardiography in idiopathic dilated
      cardiomyopathy.
AB  - In patients with chronic heart failure, myocardial contractile responsiveness to
      dobutamine is diminished as a result of beta-receptor desensitization due to
      chronic adrenergic activation. Changes in beta-receptor effector mechanisms are
      more marked in idiopathic dilated cardiomyopathy (IDCM) than in ischemic dilated
      cardiomyopathy. As the magnitude of the dobutamine effect is proportional to the
      severity of left ventricular systolic dysfunction, the heterogeneous cardiotonic
      effects of dobutamine in IDCM may represent different evolutive stages of a
      progressive disease process. On the basis of this pathophysiologic background,
      some studies were undertaken to investigate the prognostic and functional
      implications of dobutamine stress echocardiography (DSE) in IDCM. Prognostic
      studies consistently suggest that myocardial response to dobutamine is related to
      the clinical outcome. However, the limited number of patients and events in the
      individual studies are important limitations. Moreover, the impact of beta
      blockers on the potential ability of DSE to predict the prognosis needs to be
      assessed. A few studies also suggest that changes in left ventricular systolic
      function parameters following dobutamine infusion are related to exercise
      tolerance, as assessed by peak exercise oxygen consumption and functional
      recovery of the failing myocardium. The data suggest that DSE is a promising
      method, which may improve the risk stratification process in patients with IDCM
      and provide further insights into the pathophysiologic mechanisms underlying
      progressive systolic pump dysfunction and exercise intolerance. Further studies
      are however needed to define the role of DSE in IDCM.

PMID- 12506521
TI  - Myocardial perfusion and metabolic changes induced by conventional right and
      biventricular pacing in dilated cardiomyopathy evaluated by positron emission
      tomography.
AB  - BACKGROUND: Biventricular pacing induces well-known effects on myocardial wall
      function, apparently providing better results in comparison with conventional
      right pacing in patients presenting with dilated cardiomyopathy (DCM). However,
      at the moment the secondary changes in myocardial metabolism induced by pacing
      devices are unclear. The aim of our study was to evaluate the possible changes in
      myocardial metabolism and perfusion induced by cardiac pacing in these patients.
      METHODS: Twenty-eight patients presenting with DCM were submitted to positron
      emission tomography. Eighteen patients were examined during cardiac pacing, 6 had
      dual chamber pacemakers implanted for conventional reasons (group A), 12
      biventricular pacemakers (group B) for resynchronization purposes; the other 10
      patients were considered as controls. Myocardial metabolism was evaluated using
      18F-fluorodeoxyglucose (FDG), by the glucose load-insulin technique and perfusion
      using 13N-ammonia (NH3), injected at rest. A visual and a semiquantitative
      analysis were performed, calculating on the basis of the regions of interest the
      septum to lateral uptake (S/L) ratio. RESULTS: In all the 6 patients of group A,
      a selective defect in FDG uptake was observed in the septum (mean S/L ratio 0.67
      +/- 0.15, p < 0.01 with respect to controls), while both the patients in group B
      and the controls presented a homogeneous distribution of FDG uptake in the
      myocardial wall (mean S/L ratio 1.01 +/- 0.10 and 0.95 +/- 0.13 respectively, p =
      NS). On the contrary, at the NH3 positron emission tomography studies no
      significant difference in myocardial perfusion was found in the three groups of
      patients, both at the visual and at the semiquantitative analysis (mean S/L ratio
      group A 1.01 +/- 0.21, group B 0.99 +/- 0.17, controls 0.94 +/- 0.11, p = NS).
      CONCLUSIONS: Our experience could suggest that, in patients with DCM,
      conventional right pacing could induce interference in the metabolism of the
      septum not correlated with perfusion changes. On the other hand, biventricular
      pacing improves myocardial wall function without interfering with myocardial
      metabolism and perfusion.

PMID- 12506522
TI  - Prognostic value of pre-discharge exercise testing and serum C-reactive protein
      in patients with unstable angina.
AB  - BACKGROUND: Both exercise testing and C-reactive protein (CRP) serum levels have
      been shown to predict clinical events in patients with unstable angina. However,
      no previous study carefully compared their relative prognostic value in this
      clinical setting. METHODS: We reviewed data of 96 consecutive patients with
      unstable angina (77 males, 19 females, mean age 63.1 +/- 9.5 years), who were
      free from clinical events during hospital stay. A symptom/sign-limited treadmill
      exercise test had been performed and CRP serum levels had been measured prior to
      discharge in all patients. RESULTS: During an average follow-up of 2.5 years
      (range 0.5-5 years), there were 8 major cardiac events (death or myocardial
      infarction) and 11 patients had recurrent unstable angina. Both exercise-induced
      myocardial ischemia [relative risk (RR) 3.02, 95% confidence interval (CI) 0.58
      15.5, p = 0.29], and CRP levels > or = 10 mg/l (RR 2.4, 95% CI 0.51-11.2, p =
      0.25) showed a non significant association with major cardiac events. Low
      workload ischemia, however, was significantly associated with major cardiac
      events (RR 8.58, 95% CI 1.66-44.2, p = 0.01) and was also the only predictive
      variable for the combined endpoint of major events and recurrent angina (RR 2.57,
      95% CI 1.02-4.44, p = 0.045). Among patients with low workload ischemia, the
      occurrence of major events was higher in those with high, compared to those with
      low, CRP levels, but the difference was not significant (28.6 vs 15.4%, p =
      0.64). CONCLUSIONS: In this study, pre-discharge myocardial ischemia at low
      workload was the single most important predictor of major cardiac events during
      long-term follow-up among patients with stabilized unstable angina. Increased
      serum CRP levels did not add further significant prognostic information in this
      specific group of patients with unstable angina, although this issue needs to be
      addressed in larger studies.

PMID- 12506523
TI  - Myocardial contrast echocardiography and quantitative videointensity analysis
      after myocardial infarction: correlation between residual myocardial perfusion,
      contractile reserve and long-term remodeling.
AB  - BACKGROUND: Previous studies have shown the important role played by
      intracoronary myocardial contrast echocardiography (MCE) in predicting the long
      term remodeling and function after myocardial infarction. The left ventricular
      volume is an important determinant of the clinical outcome following an acute
      event. No data, however, are available on the role of intravenous MCE in this
      regard. METHODS: Ten consecutive patients with an anterior myocardial infarction
      were studied using low-dose dobutamine stress echocardiography (Dob) and
      intravenous MCE 8 +/- 4 days after the acute event. In all patients the left
      anterior descending coronary artery (LAD) was identified as the infarct-related
      vessel. A LAD score was generated using the percent residual stenosis and its
      location (proximal, mid, distal portion). Quantitative myocardial videointensity
      plots were then generated for each of the 12 ventricular segments analyzed, while
      the volumes were assessed during Dob and after 8 +/- 4 months. A higher peak
      intensity in the dysfunctioning muscle, during intravenous MCE infusion, was
      assumed to reflect a greater myocardial blood volume. RESULTS: Despite no change
      in the wall motion score index (WMSI), the percentage changes in systolic volumes
      during inotropic stimulation showed a linear relation with the LAD score.
      Furthermore, a normalized myocardial gray level in the asynergic region, taken as
      the plateau value of the videointensity time curve, showed an inverse
      relationship with the percentage changes in systolic volumes at follow-up.
      CONCLUSIONS: The residual microcirculation in the dysfunctioning muscle,
      quantitatively assessed at intravenous MCE 8 +/- 4 days after the acute event,
      has the potential of predicting chronic remodeling following an anterior
      myocardial infarction, irrespective of changes in the WMSI. The product of the
      degree of the residual infarct-related artery stenosis and its proximity predicts
      the ventricular volume response during low-dose Dob.

PMID- 12506524
TI  - Clinical features and prognosis associated with a preserved left ventricular
      systolic function in a large cohort of congestive heart failure outpatients
      managed by cardiologists. Data from the Italian Network on Congestive Heart
      Failure.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical characteristics, 1
      year prognosis and therapeutic approach of heart failure with a preserved left
      ventricular systolic function in a large multicenter registry of patients
      referred to specialized heart failure clinics. METHODS: The study population
      consisted of 5164 outpatients (mean age 62 +/- 12 years, 78.8% male, 28.1% in
      NYHA functional class III-IV) with an available left ventricular ejection
      fraction (LVEF) measurement at the initial evaluation for enrollment in the
      Italian Network on Congestive Heart Failure. A 1-year follow-up was available for
      2390 patients. RESULTS: 2859 out of 5164 patients (55.4%) had an LVEF < 35%, 1618
      (31.3%) had an LVEF between 35 and 45%, and 687 patients (13.3%) had an LVEF >
      45%. Patients with an LVEF > 45% were significantly older, more often female and
      presented a significantly higher prevalence of a hypertensive etiology, obesity
      and atrial fibrillation. The severity of the clinical picture, as indicated by a
      lower prevalence of NYHA class III-IV (17.2 vs 35.6%, p = 0.001) and a third
      heart sound (14.8 vs 33.5%, p = 0.001), was less in patients with an LVEF > 45%.
      The therapeutic approach differed significantly, with a larger use of calcium
      antagonists and beta-blockers in patients with an LVEF > 45%, while ACE
      inhibitors, diuretics and digoxin were more often prescribed to those with an
      impaired LVEF. The 1-year mortality and morbidity (all cause and congestive heart
      failure worsening hospitalizations) were significantly lower in patients with a
      preserved left ventricular systolic function compared to those with left
      ventricular systolic dysfunction (8.9 vs 18.8% for mortality, p = 0.001, and 8.3
      vs 16.5% for hospital readmissions due to worsening congestive heart failure, p =
      0.001, respectively). CONCLUSIONS: Patients with congestive heart failure and a
      preserved left ventricular systolic function seem to constitute a distinct
      population not infrequently presenting even in the clinical setting of
      specialized heart failure clinics. Further studies are needed to establish a
      definitive and standardized diagnosis and the most appropriate therapy for
      congestive heart failure with a normal LVEF.

PMID- 12506525
TI  - Continuous recording of dicrotic and pulse pressures during head-up tilting test:
      the vasodepressive profile. Preliminary data.
AB  - BACKGROUND: The aim of this study was to assess whether a non-invasive automatic
      evaluation of the pulse wave characteristics could provide clinical clues when
      monitoring the hemodynamic adjustments to head-up tilting. METHODS: A continuous
      assessment of the peripheral pulse wave characteristics (systolic, diastolic,
      dicrotic and pulse pressures) in 8 control subjects with a negative response to
      head-up tilting (60 degrees for 45 min) compared to 13 syncopal patients with a
      vasodepressive one was performed. RESULTS: Controls exhibited, when up-tilted, an
      increase in blood pressure as well as in the dicrotic and pulse pressures and no
      changes in heart rate. On the contrary, syncopal patients showed a progressive
      increase in heart rate associated with a progressive decrease in dicrotic
      pressure and a trend towards lower values of pulse pressure, but no changes in
      systolic pressure. Thereafter and until the pre-syncopal symptoms supervened, the
      systolic, diastolic and dicrotic pressures progressively declined. A decrease in
      dicrotic pressure mainly characterized the early vasodepressive response while
      its increase identified the negative one. CONCLUSIONS: Our data, even though
      preliminary, strongly suggest that automatic hemodynamic evaluation is to be used
      in the clinical setting as a monitor of the sudden changes in blood pressure
      induced by head-up tilting. Furthermore, the dicrotic and pulse pressures, even
      those measured during the early phases of the test, should be considered as non
      invasive parameters characterizing the vasodepressive response to head-up
      tilting.

PMID- 12506526
TI  - Refractory angina with severe left ventricular dysfunction: a case for
      percutaneous transseptal ventricular assistance supported revascularization.
AB  - A 73-year-old female patient with medical refractory angina, severe multivessel
      disease and a critically depressed left ventricular function (ejection fraction
      30%) was admitted to our hospital. Considered a poor candidate for surgical
      revascularization, she underwent urgent high-risk revascularization supported by
      use of a novel percutaneous left ventricular assist system.

PMID- 12506527
TI  - Different types of coronary artery wall injury following cutting balloon
      angioplasty.
AB  - The cutting balloon is a device that enlarges atherosclerotic coronary arteries
      by a combination of plaque incision and dilation. This peculiar mechanism would
      account for a better immediate result achieved at the cost of minimal vessel wall
      trauma. Coronary perforation is however a potential complication. No systematic
      data have been reported as to which angiographic lesion characteristic may
      predict the occurrence of complications after cutting balloon angioplasty. This
      case report study deals with different types of coronary artery wall injury
      complicating cutting balloon angioplasty and detected by intravascular
      ultrasound.

PMID- 12506528
TI  - Secundum atrial septal defect and pulmonary hypertension in an 86-year-old woman:
      a case report and review of the literature.
AB  - A case of well tolerated secundum atrial septal defect in a woman who died at 86
      years of age is described and the lesions responsible for pulmonary hypertension
      are discussed. Previous reports of over-70-year-old patients with untreated
      secundum atrial septal defect are also reviewed.

PMID- 12506529
TI  - Acute hepatitis complicating intravenous amiodarone treatment.
AB  - We describe a case of acute hepatitis after a loading dose of intravenous
      amiodarone. An 83-year-old woman was admitted in emergency for recent-onset
      atrial fibrillation associated with left ventricular failure. Twenty-four hours
      after having started parenteral amiodarone, she developed biochemical alterations
      indicative of severe hepatic cytolysis associated with impairment of the
      synthetic capacity which rapidly reverted after suspension of the drug. No
      clinical sign or symptom of hepatopathy was noted except for mild icterus. A
      review of the literature regarding amiodarone-related hepatotoxicity is reported.

PMID- 12506530
TI  - Ginkgo biloba-induced frequent ventricular arrhythmia.
AB  - The use of herbal medications is becoming ever more widespread, but data for them
      are not yet as robust as for conventional drugs. The available safety information
      indicates that potential side effects of such use can be due to allergic
      reactions and bleeding. In this report, a case of frequent ventricular
      arrhythmias probably due to Ginkgo biloba is presented. The patient complained of
      palpitations twice in a month and on both occasions symptoms and
      electrocardiographic evidence of ventricular arrhythmias resolved with
      discontinuation of Ginkgo biloba. This case underlines that continuing research
      is needed to elucidate the pharmacological activities of the many herbal remedies
      now being used.

PMID- 12506531
TI  - The first 200 days: cancer leadership in Ontario.

PMID- 12506532
TI  - Emotional intelligence--how well do we know ourselves and how we relate to
      others?

PMID- 12506533
TI  - Leadership competency models: roadmaps to success.
AB  - Competency models, a combination of identified skills, knowledge and attributes
      required for successful role performance, lend a roadmap for success to leaders
      of today and the new leaders of tomorrow. In healthcare, where the environment is
      ever-changing, and the pool of qualified leaders is limited and shrinking,
      competency models help to identify required areas of strength for success in
      performance. The Peterborough Regional Health Centre (PRHC) underwent a
      leadership reorganization in 2001, structuring all leaders into positions based
      on a corporate competency model. Leaders completed self-assessment portfolios and
      were shifted into roles emphasizing job-person fit, competencies, personal
      preference and organizational principles and accountabilities. The literature
      suggests that evaluations are rarely performed after corporate reorganizations,
      and when they are, they rarely measure indicators that are directly related to
      outcomes. In response to this, PRHC has structured an evaluation of the
      reorganization in two phases. The first phase is focused on process changes that
      are a direct result of the reorganization. The second phase, ongoing over 24
      months, is focused on outcomes that are resulting from the reorganization.

PMID- 12506534
TI  - Interview by Bob Bell.

PMID- 12506535
TI  - Making choices in healthcare: the reality of scarcity.
AB  - Processes are required to aid decision-makers in better managing existing
      resources in healthcare. To date, limited research has informed priority setting
      at the macro level, across broad service areas, within health organizations. As
      part of a participatory action research project, a macro-level resource
      allocation framework was developed and implemented in the Calgary Health Region
      (CHR). The approach relies on an expert panel of managers and clinicians who are
      charged with identifying, on the basis of evidence and local information, how
      resources might be reallocated to improve population well-being. The framework
      developed was seen as an improvement over historical allocation processes.

PMID- 12506537
TI  - Vision and grip: demand management in the U.K. National Health Service.

PMID- 12506536
TI  - Managing the demand for healthcare in Canada.

PMID- 12506538
TI  - Issues in the governance of Canadian hospitals, Part 1: Structure and process.
AB  - Boards that develop robust structures and processes for governing their hospitals
      lay the foundation for: Long-range success. Responsible fiscal stewardship.
      Provision of a high quality of care. Effective governance will facilitate and
      enhance a board's advocacy for the hospital. In upcoming articles, we will
      examine these three remaining elements of effective governance in greater detail.

PMID- 12506539
TI  - Governance as an instrument of successful organizational integration.
AB  - In July 1997 the Health Services Restructuring Commission (HSRC) issued a formal
      direction to the Wellesley Central Hospital to relinquish the operation and
      management of its programs and services to St. Michael's Hospital. This event
      propelled staff and volunteers into four years of unrelenting efforts to bring
      together the mission, vision, values, human resources, clinical programs and
      broad communities of these two very unique and long-standing organizations.
      Looking back, the result was arguably one of the most successful hospital mergers
      in the province at that time. A number of factors were responsible for this
      outcome. The tremendous value of a strong and integrated governance team clearly
      stands out as one of the most pivotal success factors. This article examines the
      principles and structures that guided the governance team and St. Michael's
      Hospital to a stronger and more vibrant future.

PMID- 12506540
TI  - Volunteer trustees: professionally recruited?

PMID- 12506541
TI  - You decide who decides....

PMID- 12506542
TI  - A flexible nursing workforce: realities and fallouts.
AB  - While policy-makers are increasingly concerned about a looming nursing shortage,
      almost half of Canada's nursing workforce is currently employed on a part-time or
      casual basis. Why are so many nurses not working full-time and providing the
      nursing care that would help to alleviate such shortages in our healthcare
      organizations? Do nurses want to work part-time, or are they driven into this by
      labour market forces, life demands, poor working conditions and policy decisions
      external to them? The answers to these questions are critical to ensure that care
      will be there for all of us. This article presents a brief analysis of flexible
      employment arrangements in nursing, particularly part-time and casual work, and
      the impact on nurses, patients and the healthcare system as a whole. Given the
      sharp increases in these work arrangements in Canada during the last decade, the
      limited discussion of these trends in the literature is both surprising and
      troublesome.

PMID- 12506543
TI  - HealthPRO electronic commerce alliance with Global Healthcare Exchange (GHX).

PMID- 12506544
TI  - Sister Elizabeth Davis: values-based leadership. Interview by Cynthia Martin.

PMID- 12506545
TI  - Michael L. J. Apuzzo, M.D.

PMID- 12506546
TI  - Introduction of the CNS president: Issam A. Awad.

PMID- 12506547
TI  - Ode to meaning and relevance.

PMID- 12506548
TI  - Black holes of the brain: how to reach challenging areas of the cerebrum.
AB  - Numerous techniques and tools can be used to access difficult areas of the
      cerebrum: skull base techniques, modern operating room equipment, and a unified
      team approach. Using these principles, challenging areas of the cerebrum can be
      approached with maximal success and minimal morbidity. These techniques are
      powerful tools in the armamentarium of neurosurgeons and can improve any
      neurosurgical approach. The basilar region remains one of the most difficult
      areas to approach. Despite its inherent complexity, lesions of the basilar region
      can be treated successfully. The far-lateral approach is used to access the lower
      two-fifths of the basilar region; the transcochlear approach is used to access
      the middle fifth of the basilar region; and the orbitozygomatic approach is used
      to access the upper two-fifths of the basilar region. Each approach beautifully
      exemplifies the principles of skull base surgery.

PMID- 12506549
TI  - Honored guest presentation: surgery of the human cerebrum: a collective
      modernity.

PMID- 12506550
TI  - Minimalist approach: functional mapping.
AB  - The ability to accurately map functional cortex both preoperatively and
      intraoperatively is an important neurosurgical challenge for the next decade. The
      central concept of preoperative mapping is to superimpose blood flow and
      electrical activation data on a three-dimensional matrix created by MR imaging
      and image processing. The gold standard, at present, is direct cortical
      stimulation, which can identify primary motor, sensory, speech, and visual
      cortices. Cortical mapping can be performed intraoperatively or through implanted
      subdural electrodes at the bedside. The tasks for the next decade include the
      validation of these preoperative techniques (fMRI, MEG, TMS, EP): 1. Correlation
      of direct cortical stimulation with advanced perioperative stimulation/monitoring
      systems, in a wide variety of cases. In addition, extension of these applications
      into intraoperative imaging systems like the GE Signa unit should also be
      envisaged. 2. Evaluation of how various pathologies such as AVMs, well
      circumscribed tumors, and infiltrative tumors affect the data obtained by these
      techniques. 3. Expansion of mapping to areas outside the primary motor and
      sensory cortices, including those referred to as "associative" and to higher
      functions collectively termed as "cognition."

PMID- 12506551
TI  - Surgical guidance now and in the future: the next generation of instrumentation.

PMID- 12506552
TI  - Endovascular tools for the neurosurgeon.
AB  - In summary, the treatment of cerebrovascular disease is markedly changing and
      neurosurgeons interested in this area of neurosurgery must adapt and evolve. This
      requires mastering a new set of tools and skills; however, the future is very
      bright for vascular neurosurgery, interventional neuroradiology and most
      importantly, our patients.

PMID- 12506553
TI  - Neurosurgical robotics.

PMID- 12506554
TI  - Honored guest presentation: quid novi? In the realm of ideas--the neurosurgical
      dialectic.

PMID- 12506555
TI  - Revelations to deformity correction and scoliosis surgery.

PMID- 12506556
TI  - Biomaterials and implantable devices: discoveries in the spine surgery arena.

PMID- 12506557
TI  - Endovascular surgery: the future without limits.
AB  - The new millennium brings with it tremendous advances in technology and
      information sharing. Various medical, surgical, and engineering specialities are
      becoming more focused, thus enabling experts in these fields to gain insight and
      understanding previously unappreciated by those who came before us. Economic and
      technologic evolution will eliminate some of the drawbacks of endovascular
      therapy, such as persistent neck remnants. It is likely that drug delivery
      systems exist that would allow maximal benefit with little or no systemic adverse
      effects. It is likely that devices are available that could minimize various
      procedural complications. We as future neurosurgeons must persist in the quest to
      find collaborations that will promote cross-fertilization and cross-pollination
      among cardiologists, neurosurgeons, physicists, radiologists, neurologists,
      engineers, and other scientists so that the technology can be translated to
      reality. It is clear that, in time, transcatheter techniques will replace many
      operations for the treatment of cerebrovascular pathologies. Let us not allow
      ourselves the luxury of time.

PMID- 12506558
TI  - Carotid artery stenting: fact or fiction.

PMID- 12506559
TI  - Endovascular therapy for vasospasm.

PMID- 12506560
TI  - Honored guest presentation: neurorestoration and the emergence of molecular and
      cellular neurosurgery.

PMID- 12506561
TI  - The evaluation of athletes with cerebral concussion.

PMID- 12506562
TI  - Honored guest presentation: the legacy of Galen of Pergamon. The neurosurgeon in
      the arena of sport.

PMID- 12506563
TI  - Kids and sports: frequently asked questions.

PMID- 12506564
TI  - Boxing and the neurosurgeon.

PMID- 12506565
TI  - Guidelines for the management of acute cervical spine and spinal cord injuries.

PMID- 12506566
TI  - Advances in minimally invasive spine surgery.

PMID- 12506567
TI  - Fractures, stenosis, and sports: guidance for participation.

PMID- 12506568
TI  - Spondylolysis and spondylolisthesis in the athlete.

PMID- 12506569
TI  - Energy sources in the posterior fossa: the role of radiosurgery.

PMID- 12506570
TI  - Reaching for Utopia and slouching towards Gomorrah.

PMID- 12506571
TI  - The ethics of fluoridation of water.

PMID- 12506572
TI  - Fluoridation of water in South Africa.

PMID- 12506573
TI  - Generic substitution--is it safe in patients at high cardiovascular risk?

PMID- 12506574
TI  - Particular care should be taken by pharmacists and physicians before introducing
      generic substitution is supported.

PMID- 12506575
TI  - Non-substitution of nifedipine slow-release preparations.

PMID- 12506576
TI  - Doctors advised not to disclose illnesses on sick certificates without patients'
      signed consent.

PMID- 12506577
TI  - Neonatal hypoglycaemia.

PMID- 12506578
TI  - Mortality profile of the geriatric unit at Universitas Hospital.

PMID- 12506579
TI  - The law is an ass.

PMID- 12506580
TI  - KZN Global AIDS Fund bid 'non-negotiable'.

PMID- 12506581
TI  - Fewer organ transplants with cost cuts.

PMID- 12506582
TI  - Heart procedure a first for South Africa.

PMID- 12506583
TI  - Fluoridation shibboleths.

PMID- 12506584
TI  - Superwarfarin poisoning--a report of 4 cases.

PMID- 12506585
TI  - AIDS vaccination--insurance implications.

PMID- 12506586
TI  - How do pregnant women expect to be addressed by doctors?

PMID- 12506587
TI  - Dual loyalties and HIV policy in South Africa--a challenge to the institutions of
      our professions.

PMID- 12506588
TI  - Critical care in South Africa.

PMID- 12506589
TI  - The association between fat distribution and ovulation.

PMID- 12506590
TI  - Adequacy of peritoneal dialysis and nutritional status in patients on continuous
      ambulatory peritoneal dialysis (CAPD).

PMID- 12506591
TI  - Dysbetalipoproteinaemia--clinical and pathophysiological features.
AB  - OBJECTIVES: Dysbetalipoproteinaemia (type III hyperlipidaemia, broad-beta
      disease) is a highly atherogenic genetic disorder of lipoprotein metabolism. It
      presents with a severe mixed hyperlipidaemia in which the ratio of total
      cholesterol to triglycerides is typically 2:1. There is a high incidence of
      atherosclerotic complications and severe hypertriglyceridaemia may cause
      pancreatitis. Highly effective therapy is available and affected families also
      benefit from genetic counselling. We present a review of our experience with
      dysbetalipoproteinaemia at the lipid clinic of Groote Schuur Hospital to enhance
      awareness of this serious condition, for which the index of suspicion should be
      raised. DESIGN: Retrospective review of case records, 1969-2001. SETTING: Lipid
      clinic of Groote Schuur Hospital, Cape Town. SUBJECTS: Patients with
      dysbetalipoproteinaemia diagnosed by the presence of cholesterol-enriched very
      low-density lipoproteins (VLDL) and/or dyslipidaemia associated with homozygosity
      for apolipoprotein E2 or carriers of the apoE2 (Arg145-->Cys) mutation. RESULTS:
      One hundred and five patients were identified, 55 of whom were male and 50
      female. The age at presentation was 48.8 +/- 11.1 years (mean, standard
      deviation). Total cholesterol was 12.0 +/- 5.5 mmol/l and plasma triglycerides
      8.3 +/- 9.8 mmol/l. The ratio (by mass) of cholesterol to triglycerides within
      VLDL was 0.52 +/- 0.17, while VLDL cholesterol to plasma triglycerides was 0.33
      +/- 0.09. Fifty patients were epsilon 2 homozygotes while 22 carried the apoE2
      (Arg145-->Cys) mutation. Palmar crease xanthomas occurred in 20% of patients,
      cutaneous xanthomas in 18%, and tendon xanthomas in 13%. Coronary artery disease
      was found in 47% of patients and peripheral vascular disease in 20%. Fibrates
      were the most commonly used hypolipidaemic agents (48%), while 31% of patients
      received combination therapy with a fibrate and statin. Statin monotherapy was
      used in 11% of patients and a few patients were treated with niacin or required
      no drug therapy. The treated cholesterol was 5.7 +/- 2.4 mmol/l, with plasma
      triglycerides of 2.7 +/- 1.9 mmol/l. CONCLUSIONS: Dysbetalipoproteinaemia is a
      highly atherogenic disorder and is extremely responsive to therapy. A significant
      proportion of dysbetalipoproteinaemia locally is caused by the apoE2 (Arg145-
      >Cys) mutation and is therefore dominantly inherited. This mutation is
      particularly prevalent in the black community where dysbetalipoproteinaemia may
      be undiagnosed in many patients. Patients with severe mixed hyperlipidaemia or
      clinical stigmata of dyslipidaemia should be assessed at a lipid clinic for a
      specific diagnosis and initiation of therapy.

PMID- 12506592
TI  - Intrapartum-related birth asphyxia in South Africa--lessons from the first
      national perinatal care survey.
AB  - BACKGROUND: The recent amalgamation of data by users of the Perinatal Problem
      Identification Programme (PPIP) throughout South Africa has culminated in the
      publication of the Saving Babies report. OBJECTIVES: To determine the absolute
      rate of death from intrapartum-related birth asphyxia, and the contribution of
      intrapartum-related asphyxia to total perinatal mortality in South African
      hospitals, and to identify the primary obstetric causes and avoidable factors for
      these deaths. METHODS: The amalgamated PPIP data for the year 2000 were obtained
      from 27 state hospitals (6 metropolitan, 12 town and 9 rural) in South Africa. In
      PPIP-based audit, all perinatal deaths are assigned primary obstetric causes and
      avoidable factors, and these elements were obtained for all deaths resulting from
      intrapartum-related birth asphyxia. RESULTS: There were 123,508 births in the
      hospitals surveyed, with 4,142 perinatal deaths among infants > or = 1,000 g,
      giving a perinatal mortality rate of 33.5/1,000 births. The perinatal mortality
      rate from intrapartum-related birth asphyxia was 4.8/1,000 births. The most
      frequent avoidable factors were delay by mothers in seeking attention during
      labour (36.6%), signs of fetal distress interpreted incorrectly (24.9%),
      inadequate fetal monitoring (18.0%) and no response to poor progress in labour
      (7.0%). The perinatal mortality rates for metropolitan, town, and rural areas
      were 30.0, 39.4 and 30.9/1,000 births respectively. The contribution of
      intrapartum-related birth asphyxia to perinatal mortality in these areas was
      10.8%, 16.7% and 26.4% respectively. CONCLUSION: The high rates of perinatal
      death from intrapartum-related birth asphyxia in South Africa are typical of
      those in underdeveloped countries, with the most serious deficiencies in rural
      areas. Most of these deaths are avoidable and the reduction of these rates
      presents an important challenge to providers of perinatal care in this country.
      Areas worthy of research and action include provision of mothers' waiting
      facilities in rural regions, improvements in fetal monitoring, partogram-based
      labour management, and the establishment of midwifery staffing norms for South
      African labour units.

PMID- 12506593
TI  - Randomised trials in the South African Medical Journal, 1948-1997.
AB  - OBJECTIVE: To describe randomised controlled trials (RCTs) published in the South
      African Medical Journal (SAMJ) over a 50-year period from 1948 to 1997 with
      regard to number, topic and quality. METHODS: We hand searched all issues of the
      SAMJ published during the study period to identify all published RCTs. OUTCOME
      MEASURES: Number, topic and quality of RCTs published from 1948 to 1997. RESULTS:
      Eight hundred and fifty-eight clinical trials were published during the period
      reviewed. Eighty-four per cent of RCTs were published as full articles. During
      the 1980s the number of RCTs published increased rapidly, with a peak of 35 in
      1985, but then declined to only 5 in 1997. The majority (92%) of RCTs were
      conducted in a hospital setting. A varied range of subjects was covered, with
      gastroenterology taking the lead and no trials in public health. The sample size
      in more than 50% of RCTs was smaller than 50 patients. Fifty-one per cent (435
      trials) used random allocation and 49% (423) quasi-random methods of allocation.
      Concealment of treatment allocation was judged to be adequate in 46% of studies
      (N = 200), blinding of observers assessing outcomes was adequate in 28% (123),
      and all the allocated test subjects were included in the primary analysis in 28%
      (123). The follow-up period was more than 1 year in 4% (17) and less than 6 days
      in 16% (71). CONCLUSIONS: Compared with other international journals the SAMJ is
      highly regarded in terms of the number of trials published. There are, however, a
      number of deficiencies in the quality of the trials.

PMID- 12506594
TI  - Willingness to participate in South African HIV vaccine trials--concerns of
      medical professionals in the Western Cape.
AB  - OBJECTIVES: To evaluate the willingness of medical doctors working at a tertiary
      hospital to participate in HIV vaccine trials, their perceptions of patients'
      willingness to participate, and the major reasons underlying these views. DESIGN:
      A self-administered, anonymous postal survey conducted in two rounds between May
      and July 2001. SETTING: A tertiary care hospital in the Western Cape. SUBJECTS:
      All medical doctors listed on the hospital's staff directory. OUTCOME MEASURES:
      Willingness to participate in, and to recruit patients into, HIV vaccine trials,
      and the reasons for this. RESULTS AND CONCLUSIONS: Of the 289 individuals
      surveyed, 80% stated either that they would not be willing to participate in HIV
      vaccine trials or that they were unsure about their participation. Meanwhile, 37%
      stated that they would be willing to recruit patients into vaccine trials. The
      most common concerns with trial participation were the possibility of vaccine
      induced infection and the possibility of testing positive for antibodies to HIV.
      The surprisingly low level of willingness to participate in trials in this sample
      of medical professionals highlights the importance of preparatory work to
      overcome substantial barriers to HIV vaccine trial participation.

PMID- 12506595
TI  - Aetiology and outcome of severe community-acquired pneumonia in children admitted
      to a paediatric intensive care unit.
AB  - OBJECTIVE: To determine the aetiological agents and outcome of severe community
      acquired pneumonia (SCAP) in children admitted to the paediatric intensive care
      unit (PICU) at Kalafong Hospital, Pretoria. PATIENTS AND METHODS: An audit was
      done after a protocol was implemented to identify the aetiological agents in
      children with life-threatening SCAP admitted to the PICU from the emergency room.
      The following investigations were done as per protocol: blood culture, culture of
      the tracheal aspirate, immunofluorescence and culture of the nasopharyngeal
      aspirate, microscopy and culture of the gastric juice for Mycobacterium
      tuberculosis, and determination of HIV status. The following data, documented
      prospectively, were obtained from patient records: date of admission, age,
      gender, weight, duration of ventilation, duration of stay in the PICU, survival
      or death, and severity of illness as determined by means of the score for acute
      neonatal physiology (SNAP) or paediatric risk of mortality (PRISM) score
      depending on the child's age. RESULTS: Twenty-three children were admitted over a
      1-year period (1 November 1994-30 October 1995). Their median age was 10 weeks
      (range 2 weeks-5 years) and the sex distribution was equal. Two children were HIV
      infected. Twenty children received mechanical ventilation for a median period of
      6.5 days (range 2-16 days). Aetiological agents were identified in 15/23 children
      (65%). Respiratory syncytial virus (RSV) was the most common pathogen, identified
      in 7/23 children, Klebsiella pneumoniae was the most common bacterial pathogen,
      identified in 5 children (2 blood cultures and 3 tracheal aspirates).
      Tuberculosis was not diagnosed. The mean PRISM score was similar in survivors and
      children who died. The case fatality rate was 30%. The 7 children who died had a
      median arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) ratio of
      94 (range 32-111) and the 16 survivors had a median ratio of 146 (range 51-252)
      (P = 0.01) on admission. Both HIV-infected children died and postmortem
      examination showed a pneumonia due to Pneumocystis carinii and cytomegalovirus.
      CONCLUSIONS: SCAP occurs in very young children. One or more pathogens were
      isolated in 65% of cases. Viral pathogens predominated, with RSV being the most
      common. The yield of positive blood cultures was low at 17%. Streptococcus
      pneumoniae and Haemophilus influenzae were not found. The case fatality rate was
      30% and death was more likely with a low PaO2/FiO2 ratio on admission.

PMID- 12506596
TI  - Effect of 1% and 2% propofol on blood lipids during longterm sedation.
AB  - OBJECTIVES: To compare the effects of 1% and 2% propofol on the maximum and
      average lipid levels, the relative frequency of hyperlipidaemia, the propofol
      dose required to achieve an equivalent degree of sedation, the pharmacodynamic
      effects at the required infusion rates, and the effect on respiratory function.
      DESIGN: Open, randomised, parallel group, multicentre comparison study. SETTING:
      Intensive care units (ICUs) at the Faculty of Medicine, University of
      Stellenbosch and at Vergelegen Medicity, Somerset West. SUBJECTS: Patients who
      were artificially ventilated for at least 72 hours in the ICUs and who required
      sedation or analgesia. OUTCOME MEASURES: Continuous intravenous infusion of 1% or
      2% propofol to provide an administration rate in the range of 1-4 mg/kg/h. The
      initial infusion rate was about 2 mg/kg/h, adjusted to achieve the appropriate
      level of sedation. RESULTS AND CONCLUSIONS: Seventy-five patients were enrolled
      in the study, of which 72 were evaluable for safety analysis and 58 were
      evaluable for efficacy analysis. The total daily dose of propofol (ml/day) in the
      2% propofol group was about 60% of that in the 1% propofol group, indicating that
      the lipid load in the 2% propofol group had only slightly more than half the
      lipid load in the 1% propofol group. Thirteen of 27 patients (48%) in the 2%
      propofol group had abnormally.

PMID- 12506597
TI  - Bureaucratic breakdown: clinical services are suffering.

PMID- 12506598
TI  - Administration can forge new direction in addiction recovery.

PMID- 12506599
TI  - Using outreach and support to improve medication compliance.

PMID- 12506600
TI  - Medical necessity: a critique of traditional approaches.

PMID- 12506601
TI  - Cost-effective prevention for children living with addiction.

PMID- 12506602
TI  - How your technology vendor can help achieve--not guarantee--HIPAA compliance.

PMID- 12506603
TI  - Using validation technology to solve the HIPAA challenge.

PMID- 12506604
TI  - Agencies reap benefits of planning ahead HIPAA. Health Insurance Portability and
      Accountability Act.

PMID- 12506605
TI  - Building bridges for the most seriously ill.

PMID- 12506606
TI  - Grandfathering can seriously damage your wealth: due diligence in mergers and
      acquisitions of medical device companies.

PMID- 12506607
TI  - [Mitochondrial diseases--a new branch of the modern medicine].
AB  - The review highlights current aspects of a large group of diseases the main
      pathogenetic element of which is an inherited or acquired disturbance of gene
      expression of nuclear or mitochondrial genome encoding mitochondrial proteins.
      The recent data on mutant genetic loci specific to the most wide spread
      mitochondrial diseases are considered. The steps of pathogenesis, include the
      mutations of nuclear or mitochondrial genes, disturbances of mitochondrial
      protein synthesis, dissipation of proton membrane potential, opening of a
      permeability transition pore, releasing of procaspases, cytochrome c, and other
      proapoptotic molecules, and finally chromatin fragmentation and apoptotic cell
      death. We discuss the possible reasons of polysymptomatic character and different
      variants of mitochondrial disease manifestations on the basis of the phenomenon
      of mitochondrial DNA heteroplasmy and metabolic compensation of the genetic
      defects. Modern biochemical methods of a mitochondrial disease diagnostics: (PCR
      amplification, polarographic research of mitochondrial respiration and oxidative
      phosphorylation, analysis and monitoring of metabolites in biological liquids)
      are characterized. The basic principles and perspectives of the treatment of
      mitochondrial diseases, (gene therapy, correction of metabolic disorders,
      application of antioxidants and neuropeptides) are described.

PMID- 12506608
TI  - [Modern approaches to pharmacotherapy of diabetes mellitus type II].
AB  - The pharmacological approaches to the treatment of type 2 diabetes mellitus were
      reviewed. Special attention was paid to the new therapeutic agents that are able
      to decrease plasma glucose levels. The possible mechanisms of the hypoglycemic
      effects are discussed. Briefly, repaginide, nateglinede and alpha-glucosidase
      inhibitors prevent postprandial hypoclycemia while thiazaolidinediones improve
      the sensitivity to insulin and vanadium compounds act as an insulin action
      enhancer.

PMID- 12506609
TI  - [Numerical euristic approach to the proteome map analysis].
AB  - The possibility of numerical-heuristic approach has been examined for proteome
      map analysis that realized by neural network processing of 2D protein
      electrophoregramms. The fetal alcohol syndrome was used to illustrate that this
      approach islatively effective for diagnostics of diseases.

PMID- 12506610
TI  - [Evaluation of preservation and the collagen structure state in the mummy
      tissues].
AB  - The content and state of collagen in skin, muscle and bone of 2500-year-old Altai
      mummies were studied. Collagen is the predominant protein in studied tissues of
      the mummies. High degree of the resistance of collagen to the effect of various
      proteases (collagenase, pronase, pepsin) and to alkline and acidic hydrolysis
      suggests on the considerable chemical modification of tissue collagen structures
      of the mummy. The possibility of increased collagen cross-linkages in tissues of
      the mummies during long-term storage and of nonenzymatic glycosylation of
      collagen leading to the formation an Amadori products and other modified
      structures are discussed.

PMID- 12506611
TI  - [Genetic heterogeneity of cytochrome CYP51 in clinical strains of Mycobacterium
      tuberculosis].
AB  - Information on the complete genome sequences of a number of organisms available
      recently offers essentially new opportunities for the development of new, highly
      effective antimicrobial compounds. In particular, the search for new effective
      antituberculosis drugs remains an important problem, due to the recent increase
      of number of patients suffering with tuberculosis. In this respect considerable
      attention is paid to the cyp51-like gene Rv0764c encoding sterol-14 alpha
      demethylase belonging to the cytochrome P450 superfamily, which has been
      discovered by computer analysis of the Mycobacterium tuberculosis genome
      sequence. We have screened 64 clinical isolates of M. tuberculosis for
      functionally relevant mutations in the coding sequence of the gene encoding Cyp
      51-demethylase by single-strand conformation polymorphism analysis (SSCP) and
      sequencing of PCR-amplified gene fragments. Structural analysis of the gene in
      the isolates revealed no mutations leading to amino acid substitutions in the
      corresponding protein. 10 isolates had a silent nucleotide substitution 114 GCT-
      >GCC. Computer analysis of cyp51 sequence of the CDC1551 strain also revealed a
      similar nucleotide substitution, which has not been mentioned previously. The
      data obtained demonstrate that the sequence of the gene is highly conserved,
      supporting the advisability of M. tuberculosis Cyp51 protein to be considered as
      a molecular target for new antitubercular drugs. The SNP found in the gene coding
      sequence may be employed in the studies of M. tuberculosis population genetics.

PMID- 12506612
TI  - [Correction of lipid metabolism in rabbits with experimental cholelithiasis].
AB  - The effect of 16-20% medicinal preparation "Equalen" on some parameters of lipid
      metabolism in female rabbits with cholelithiasis induced by 40% clamp of common
      bile duct was investigated. The total course of Equalen administration for 90-120
      days included daily oral administration of Equalen for 7 days followed by 3-4 day
      interval. The optimal dose was 1.5 ml per day (the effective range of doses
      varied from 1.2 to 2.0 ml). Such treatment resulted in disappearance of large and
      medium sized cholesterol formations from gallbladder, normalization of lipid
      metabolism in organs of hepatoenteric system and lipid composition of bile.

PMID- 12506613
TI  - [A drop of mink complement kills a mouse].
AB  - The phenomenon of fast death of mice after parenteral administration of mink
      serum was explained by high activity of mink complement in particular by
      unusually high activity of its alternative pathway of activation. The presence of
      antibodies to mouse erythrocytes in mink serum was necessary precondition for
      their lysis under action of mink complement by classical and alternative
      pathways. However, removal of these antibodies resulting in cancellation of
      hemolysis did not effect toxicity of mink serum for nice in vivo. Partial
      decomplementization of mink serum zymosan completely prevented death of animals.

PMID- 12506614
TI  - [Myeloperoxidase in the human placenta at preterm labor].
AB  - In the present study the level of myeloperoxidase in the human placenta at
      premature was investigated. Mycloperoxidase content did not depend on its
      localization in placenta and decreased at premature labour. It is suggested that
      the decrease in the myeloperoxidase content in placenta results in the weakening
      of antimicrobial barrier in the system mother-placenta-fetus and plays an
      important role in pathogenesis of premature delivery at later term.

PMID- 12506615
TI  - [Levels of autoantibodies to glutamate receptors and immunological blood
      parameters in patients with epilepsy].
AB  - The role of glutamate receptors in the brain spiking activity was evaluated. The
      electroencephalographic (EEG) spiking activity was monitored and autoreactive
      antibodies (aAbs) to subunits of glutamate receptors were assessed in the blood
      serum of epileptic and ischemic stroke patients. We showed that the level of GluR
      autoantibodies in blood serum of patients correlates to the intensity of the
      brain paroxysmal activity. These data confirm our previous observations. The
      level of GluR1 aABs has been proposed as a specific biomarker typical for
      epilepsy. This approach could be recommended as an additional criterion for
      diagnostic of nervous diseases such as epilepsy and ischemic stroke.

PMID- 12506616
TI  - [Regulation of ceruloplasmin activity in oncogynecological diseases].
AB  - Serum ceruloplasmih (CP) and anti-CP antibody levels were studied by the oxidase
      method in 18 healthy women and in 86 women with gynecological tumors. The results
      demonstrate that: 1) Serum CP concentrations increased in endometrial and ovarian
      cancer, in benign ovarian tumors and to a lesser extent in mioma of uterus. 2)
      Serum CP antibodies were found out in both benign tumors and cancer cases. 3)
      There was positive linear correlation between serum levels of CP and anti-CP
      antibodies in endometrial and ovarian cancers, and in benign ovarian tumors.

PMID- 12506617
TI  - [On June 21, 2002 Russia was declared a poliomyelitis-free zone].

PMID- 12506618
TI  - [Pathogenicity islands in opportunistic Enterobacteria].
AB  - The presence of fragments of genomes hlyA, hlyB, papAH, papC, sfaG, sfaA and kps
      MT, associated with the pathogenicity islands of Escherichia coli, in clinical
      strains of other genera of the family Enterobacteriaceae, has been experimentally
      evaluated with the use of PCR. The presence of DNA fragments specific to the
      known genes of the pathogenicity clusters of E. coli in representatives of the
      genera Citrobacter, Enterobacter, Hafnia, Klebsiella, Morganella, Proteus,
      Providencia, Serratia and Yersinia of rarely occurring groups has been
      established. In Enterobacteriaceae cultures isolated from the intestine amplicons
      homologous to hlyB were detected significantly less frequently than among strains
      of nonintestinal origin. In Enterobacteriaceae strains isolated in respiratory
      pathology amplicons of the pili gene (sfaG) were detected significantly more
      frequently than in collection cultures. The total evaluation of the detection
      rate of the genes of pathogenicity islands among Enterobacteriaceae clinical
      strains under study in comparison with E. coli showed that they occurred
      significantly less frequently. Klebsiella spp. were found to differ most
      essentially from E. coli as regards the occurrence of fragments of the genes of
      pathogenicity islands. The conclusion was made on the high probability of genetic
      exchange in DNA fragments between different species of bacteria with
      corresponding changes in their pathogenicity.

PMID- 12506619
TI  - [Monitoring of etiological agents of acute enteric infections in the Moscow
      region].
AB  - The fecal microflora of patients with acute enteric infections (AEI) has been
      examined on the territory of the Moscow region. The pathogens of high, moderate
      and low priority levels have been detected. As revealed in this study, shigellae,
      salmonellae, enteropathogenic and enteroinvasive Escherichia are the etiological
      agents of bacterial diarrheas on the territory of the Moscow region. The dynamics
      of the etiological agents of AEI in the region has been established.

PMID- 12506620
TI  - [Effect of metal oxides on the growth, hemolytic and serologic properties of
      Klebsiella pneumoniae].
AB  - Silicon, dysprosium, germanium, yttrium, iron, cobalt, samarium, lutecium oxides,
      as well as the mixture of 8 metal oxides, at a concentration of 20 g/l were found
      to produce a stimulating or inhibiting effect on the growth of K. pneumoniae
      strains 204 and K-9. Silicon, dysprosium, germanium and yttrium oxides were shown
      to stimulate the growth of K. pneumoniae strain 204. Iron, cobalt, samarium and
      lutecium oxides, as well as the mixtures of all oxides under study, inhibited the
      growth of this strain. Silicon, samarium and lutecium oxides produced no effect
      on the growth of K. pneumoniae strain K-9; at the same time germanium and yttrium
      oxides stimulated the growth of these bacteria, while dysprosium, iron, cobalt
      oxides, as well as the mixture of all oxides, inhibited their growth. The
      presence of metal oxides did not change the serological activity of the cultures
      of both strains growing old, i.e. by 24 hours of their growth. The addition of
      silicon, germanium and iron oxides to the culture medium increased the hemolytic
      activity of K. pneumoniae strain K-9 seven to ninefold in comparison with the
      control grown in a synthetic nutrient medium without metal oxides. The comparison
      of these two strains (K-9 and 204) revealed that K. pneumoniae strain K-9
      possessed greater hemolytic activity.

PMID- 12506621
TI  - [Action of Spirulina platensis on bacterial viruses].
AB  - The impact of the biomass of the blue-green microalga (cyanobacterium) S.
      platensis on bacteriophage T4 (bacterial virus) has been evaluated. The study
      revealed that the addition of S. platensis biomass into the agar nutrient medium,
      followed by sterilization with 2% chloroform and thermal treatment, produced an
      inhibiting or stimulating effect on the reproduction of the bacteriophage in
      Escherichia coli B cells, depending on the concentration of S. platensis and the
      multiplicity of phage infection, as well as on the fact whether the microalgae
      were added during the first cycle of the development of the virus. The
      reproduction of the bacteriophage in E. coli B was influenced by the method and
      duration of the sterilization of the nutrient medium with S. platensis.

PMID- 12506622
TI  - [Detection of natural foci of babesiosis and granulocytic ehrlichiosis in
      Russia].
AB  - The use of microscopy, infection of golden hamsters and the polymerase chain
      reaction made it possible to find out that about 30% of common red-backed voles
      (Clethrionomys glareolus), inhabiting the taiga forests of the southern part of
      the Western Urals (the Chusovskoi district of the Perm region), were infected
      with Babesia microti and simultaneously (a third of them) with Ehrlichia
      (Cytoecetes) phagocytophila, the causative agent of granulocytic ehrlichiosis.
      The sequencing of 18S rDNA of strain "Mys", isolated in Russia, revealed its
      identity to American B. microti strain GI, pathogenic for humans. The main vector
      supporting the circulation of B. microti in the natural foci in the region where
      these investigations were conducted was, seemingly, the tick Ixodes
      trianguliceps, Thus, for the first time the data proving the presence of
      reservoir hosts infected with B. microti and granulocytic E. phagocytophila,
      pathogenic for humans, in Russia were presented.

PMID- 12506623
TI  - [Crimean hemorrhagic fever in the Rostov region: epidemiological zoning and the
      activity of natural foci].
AB  - The epidemiological zoning of the territory of the Rostov region has been made
      with the use of the epidemic process patterns and the data indicating the links
      between the landscape and the natural focus of infection. The spread of infected
      ticks has been established. The participation of several carrier species in the
      circulation of Crimean-Congo haemorrhagic fever virus has been confirmed. The
      mosaic character of their distribution and different levels of their
      contamination is of great prognostic importance. These data will be used for the
      improvement of epidemiological surveillance in working out the tactics of
      epizootological surveys and organization of prophylactic measures.

PMID- 12506624
TI  - [Genetic typing of Mycobacterium tuberculosis strains by spoligotyping and genome
      fingerprinting techniques].
AB  - A total of 122 M. tuberculosis clinical drug-resistant strains isolated in
      Central Russia were studied by spoligotyping and genome fingerprinting
      techniques. According to spoligotyping results 77% of M. tuberculosis strains
      were distributed to 13 oligotypes, while 23% of these strains were found to form
      unique patterns. Most of them belonged to the families Beijing and Haarlem (43.4%
      and 13.9% respectively). The patterns of the strains of oligotype 12 (7F-7F-7E-0E
      78-3E) were identical to those of the strains isolated in Brazil, France and the
      Netherlands. The strains of the spoligotype 22 (7F-1E-7F-7F-07-3E) had the
      patterns identical to those of the strains of group S13, also isolated in Brazil.
      According to genome fingerprinting 31.4% of the strains were found to belong to
      clusters with the similarity coefficient equal to 1. The strains belonging to
      genotypes W and A1 were found to prevail in the analyzed group.

PMID- 12506625
TI  - [Frequency dynamics of foxes as a factor of epizootic risk of rabies].
AB  - During the period preceding the year 1998 when the peak values of the rabies
      incidence were registered in the Moscow region, a noticeable increase in fox
      frequency and the density of their population occurred, especially in 3 endemic
      areas of the north-western zone. Considering the fact that this zone was endemic
      for rabies, an increased density of the fox population was, most probably, the
      critical factor of the epizootological risk and the main cause of the emergency
      situation in rabies in 1998. The data obtained in this investigation may serve as
      a real basis for the prediction of the epizootic situation.

PMID- 12506626
TI  - [Specific features of the HIV infection epidemic in Moscow].
AB  - Retrospective analysis of the epidemic of HIV infection in Moscow allowed to mark
      out two periods: the first--from 1987 to 1993 and the second one--from 1994 to
      2000. The characteristic feature of the first period of the epidemic was the
      sexual transmission of the agent mainly among homosexuals; the most affected
      group were persons aged 20-39 years and the number of AIDS patient decreased with
      a simultaneous growth in lethality. During the second stage of the HIV infection
      epidemic changes in the prevailing transmission routes of the agent occurred:
      injection drug addicts took the leading role. Changes in the ratio of HIV
      infected men and women took place along with active involvement of persons aged
      13-18 years into the epidemic process. The established changes in the
      epidemiological situation require corrections in the strategy and tactics of
      epidemic control and prophylactic measures.

PMID- 12506627
TI  - [State of collective immunity to poliomyelitis in Moscow donors].
AB  - Immunity induced by immunization with oral poliomyelitis vaccine has long been
      considered to last for life, similarly to immunity developing after infection
      with wild poliomyelitis virus. Vaccine virus cannot circulate among the immune
      population for a long time. The vaccination of children against poliomyelitis,
      carried out in the course of many years, has made it possible to suggest that a
      considerable number of immune persons were present among the adult population.
      The examination of 1,030 Moscow donors has revealed that antibodies to
      poliomyelitis virus of types 1, 2 and 3 were detected in 47.3%, 45.5% and 76.4%
      of the examinees respectively, the values of the average geometric titers being
      low. It is known that passages of poliomyelitis vaccine virus through nonimmune
      persons may result in emergence of revertant viruses with increased
      neurovirulence. The nonimmune adult population, especially the mothers of
      vaccinated and revaccinated children, may serve as favorable environment for the
      circulation of vaccine viruses and the appearance of revertant viruses.

PMID- 12506628
TI  - [Characteristics of antitoxic and antibacterial immune response in nontoxic forms
      of oropharyngeal diphtheria].
AB  - The enzyme immunoassay system (EIA) for differentiation of antibodies in
      therapeutic heterogeneous antitoxic serum and antibodies to Corynebacterium
      diphtheriae toxigenic strains in patients and carriers was developed. The use of
      EIA permitted the dynamic evaluation of the characteristics of humoral antitoxic
      and antibacterial immune response in 50 patients with the localized and
      disseminated forms of stomatopharyngeal diphtheria and 14 "healthy" carriers of
      toxigenic C. diphtheriae. As revealed in this study, the symptoms of the disease
      in patients with disseminated forms of stomatopharyngeal diphtheria developed in
      the presence of statistically significant low quantitative values of antitoxic
      and antibacterial antibodies to C. diphtheriae antigens. In the group of patients
      with the localized forms of the disease the initially low level of antitoxic
      antibodies was detected with the concentration of antibacterial antibodies
      remaining unchanged. During the period of convalescence the levels of antitoxic
      antibodies in both groups reached those of healthy persons. In case of localized
      forms of the disease the level of antibacterial antibodies decreased as compared
      with healthy persons, starting from the second week of the disease. The period of
      convalescence in the disseminated forms was characterized by the low
      concentration of antibacterial antibodies. Carrier state was formed in the
      presence of high levels of antitoxic antibodies and significantly low levels of
      antibacterial ones.

PMID- 12506629
TI  - [Effect of purified staphylococcal toxoid preparation on the in vitro production
      of interferon by leukocytes from patients with atopic dermatitis].
AB  - The impact of purified staphylococcal toxoid (PST) on the in vitro production of
      interferon (IFN) by blood leukocytes was evaluated. PST was found to produce a
      stimulating effect on the production of alpha-IFN in patients with atopic
      dermatitis (AD): in 88% of cases a two-fivefold increase in IFN production was
      observed in AD patients in comparison with healthy donors. In addition, the
      incubation of leukocytes obtained from atopic and nonatopic patients with PST was
      shown to stimulate the production of gamma-IFN by these leukocytes fivefold, on
      the average. These results give theoretical basis for use of PST (as an inducer
      of endogenic IFN) for AD patients treatment.

PMID- 12506630
TI  - [Effect of thymic peptides on the functional activity of phagocytic cells of
      donor peripheral blood].
AB  - The direct action of synthetic peptide preparations, analogous to thymic
      hormones, on the functions of phagocytic cells was studied. The preparations
      Thymogen, Neogen and Thymodepressin in a dose of 10 mM produced a stimulating
      effect on the ingestive activity of the neutrophil, but not monocytic,
      population. All three preparations also enhanced the formation of oxygen
      metabolites registered in the luminol-dependent chemiluminescent analysis. The
      characteristics of spontaneous chemiluminescence (CL) reflecting the basal level
      of the synthesis of the active forms of oxygen and CL induced by opsomized
      zymosan significantly increased also in those cases when the preparations were
      used in a dose of 10 mM. The level of the synthesis of hydrogen peroxide in
      individual cells could be appraised by the intensity of the luminescence of
      dichlorofluorescein diacetate (DCF-DA), evaluated with the use of flow cytometry.
      All preparations produced a stimulating effect on the formation of hydrogen
      peroxide in monocytes. The reaction of neutrophils was even more active: Neogen
      (10 mM) produced the twofold change in the intensity of the luminescence of DCF
      DA) in neutrophils, Thymogen and Thynodepressin increased the average intensity
      of the luminescence of DCF-DA by 80% and 60%, respectively.

PMID- 12506631
TI  - [Immunobiological properties of Burkholderia pseudomallei and Burkholderia mallei
      capsular substances].
AB  - The biopolymer composition, immunotropic and immunogenic properties of the
      fractions of B. pseudomallei and B. mallei were under study. The first two
      capsular fractions of these agents were found to be similar in their biopolymer
      composition that was indicative of their close relations. At the same time the
      causative agents of glanders proved to have decreased content of high molecular
      glycoproteids and LPS fragments. In the causative agents of melioidosis, capsular
      fractions K3 and K4 were characterized by the domination of proteins with a
      molecular weight of 42-25 kD. Fraction K4 in B. pseudomallei and fraction K1 in
      B. mallei had pronounced immunosuppressing properties ensuring the protection of
      encapsulated microbial cells in the body. The biopolymers forming fractions K1,
      K2, K3 in B. pseudomallei and fraction K2 in B. mallei were characterized by
      immunomodulating properties.

PMID- 12506632
TI  - [Enzyme immunoassay system for detection of staphylococcal enterotoxin, type C].
AB  - An enzyme immunoassay (EIA) system for detection of staphylococcal enterotoxin,
      type C, has been developed. The sensitivity of the system is 1 ng/ml. The optimum
      EIA parameters have been worked out. The absence of false positive results with
      heterologous toxins confirms the specificity of the assay system. The possibility
      of the detection of staphylococcal enterotoxin, type C, in staphylococci isolated
      from different sources has been shown.

PMID- 12506633
TI  - [Clinical course and treatment regimes of Salmonella infection in children].
AB  - Salmonella infection in children caused by polyresistant S. typhimurium strains
      is characterized by a highly severe course with possible complications. In the
      treatment of young children with salmonellosis the use of the locally
      manufactured biologically active additive Bektit-M, possessing adsorption
      capacity, is recommended. The use of this preparation in complex treatment has
      made it possible to establish its clinical effect and positive influence on the
      biochemical characteristics of the blood.

PMID- 12506634
TI  - [Study on the effect of a biostimulant on the growth and toxigenic function of
      Clostridium tetani strain Copenhagen-471].
AB  - Bakstim, a new biostimulating preparation obtained from the organs of the immune
      system of animals, was developed. The impact of Bakstim on the growth and
      toxigenic function of C. tetani production strain Copenhagen-471 was evaluated.
      The addition of the preparation to Gluzman commercial medium for obtaining
      tetanus toxoid led to an increase in the yield of bacterial biomass from 1.9 to 4
      fold and an increase in the toxoid production from 2 to 2.8-fold. The optimum
      concentration of this biostimulant ensuring the maximum yield of tetanus toxin
      from the production culture was determined (1,000 mg/l). Bakstim will supposedly
      be used as additive to nutrient media for the production of tetanus toxoid.

PMID- 12506635
TI  - [Study of the effectiveness of methods of purification of metalloprotease
      produced by Bacillus subtilis].
AB  - The effectiveness of the purification of proteolytic enzyme produced by B.
      subtilis production strain 3H in different nutrient media was evaluated. As
      revealed in this study, the use of the initial material obtained in peptone
      nutrient medium made it possible to obtain proteolytic enzyme with the highest
      specific activity by the methods of salting out, gel and ion-exchange
      chromatography, but the use of these methods on a production scale led to the
      deterioration of purity characteristics. Changes in the nutrient medium
      composition used for the cultivation of the production strain resulted in greater
      effectiveness of the purification methods. The highly purified preparation of
      metalloprotease with specific activity exceeding that of available commercial
      preparations more than twofold was obtained.

PMID- 12506636
TI  - [Characterization of Vibrio cholerae cultures isolated in foci of cholera in the
      city of Kazan].
AB  - During the period of the registered outbreak of cholera in 2001 in Kazan 171 V.
      cholerae cultures were isolated in the focus of the infection (from patients,
      carriers and 7 environmental objects). The use of the basic and additional tests,
      including the polymerase chain reaction, made it possible to establish the
      circulation of V. cholerae, phagovar 15, in the focus of the infection. The
      strain isolated from the water reservoir Azino-1 in Kazan was identical in its
      properties to the epidemically dangerous strains isolated from patients. On the
      whole, the data obtained in the identification of the strains showed that the
      cultures isolated from patients, vibrio-carriers and environmental objects were
      identical.

PMID- 12506637
TI  - [Serine proteases of Gram-negative bacteria: structure, mechanisms of secretion,
      biological activity].
AB  - Current data on the characterization of bacterial serine proteases, forming the
      family of proteins with specific structural and functional features and secreted
      by type V (autotransport), are presented. The expression of many of these
      proteases is believed to be linked with pathogenicity of Gram negative bacteria,
      which necessitates their further study with a view to obtain more profound
      concepts. These enzymes have been shown to facilitate the bacterial colonization
      of the skin and mucous membranes. They are believed to be linked with the
      resistance of microorganisms to lysosomal proteolysis by phagocytes and their
      ensuing dissemination in the course of the infectious process. Serine proteases
      split coagulating factor V and enhance the permeability of blood vessels, thus
      inducing the hemorrhagic syndrome. The detailed study of serine proteases is
      closely linked with the prospects of the development of protease inhibiting
      preparations aimed at the suppression of the pathogenetic activity of proteases
      by their blocking or by affecting the mechanisms of their secretion.

PMID- 12506638
TI  - [Bacterial zoonoses with natural focality: current trends in epidemic
      manifestation].
AB  - Current trends in epidemic manifestation of some bacterial zoonoses with natural
      focality and their role in human infectious pathology have been reviewed and
      analyzed. Update information on the etiological agents of "emerging" and "re
      emerging" infections--Astrakhan spotted fever, bartonellosis, ixodes tick-borne
      borrelioses, monocytic erhrlichiosis and canine brucellosis, recently isolated on
      the territory of Russia, is presented. The main factors at play in the process of
      urbanization of bacterial zoonoses are discussed.

PMID- 12506639
TI  - [Microbial ecology of the vagina].
AB  - In this review recent information on relationships between the vaginal
      environment and microflora, including new taxonomic groups of microorganisms, is
      updated. The role of normal microflora in formation of vaginal colonization
      resistance and possible participation of some representatives of normal
      microflora, mainly nonsporulating anaerobic organisms, in the development of
      perinatal, neonatal and gynecological infectious complications are considered.

PMID- 12506640
TI  - [Blood serum cholesterol and the state of the immune system].
AB  - This review deals with information on the relationship of the immunity system and
      the lipid transport system. The data of literature and the results obtained by
      the authors indicated that an elevated level of cholesterol in the blood serum is
      associated with the increased activity of the immunity system. On the one hand,
      lipids and their metabolites produce an immunomodulating effect and, on the other
      hand, biologically active molecules, synthesized by immunocompetent cells in the
      process of their activation and proliferation, regulate lipid metabolism.

PMID- 12506641
TI  - [Flow laser cytometry for evaluation of the human immune system].
AB  - Some flow laser cytometry (FLC) techniques intended for studies of the immune
      system cells are reviewed. A widespread analytical method is the phenotyping of
      lymphocytes by the markers they express. The use of FLC permits the evaluation of
      practically all functional parameters of immunocompetent cells. Thus, to analyze
      their ingestive and microbicidal activity fluorochrome-labeled microorganisms are
      used. The apploication of indicator dyes makes it possible to evaluate calcium
      mobilization and formation of active forms of oxygen. FLC is used for the
      identification of cytokines inside the cell and in the medium. The authors
      propose tests for the analysis of the proliferative activity of lymphocytes, the
      cytotoxicity of natural killers, the evaluation of apoptosis and protein
      processing with monocytes/macrophages.

PMID- 12506642
TI  - [Some molecular-biological and immunological aspects of Aleutian disease of
      mink].
AB  - Information on the development of the infectious process in the Aleutian disease
      of minks (ADM) on the molecular level, are updated. In particular, the decisive
      role played by the ABM virus infection of the cells of the immune system (B
      lymphocytes, macrophages, follicular dendritic cells) and the possible
      involvement of the mechanism of the antibody-dependent aggravation of this
      infection are pointed out. In addition, the role of the weak ADM virus promoter
      p36, the immune status of minks and their age in the determination of the acute
      or "slow" character of the course of the disease are considered.

PMID- 12506643
TI  - [Modern proof of the infectious etiology of disease and Koch's postulates].

PMID- 12506644
TI  - [Anthropogenic transformation of the environment and morbidity of infections with
      natural focality in the Ul'ianovsk region].

PMID- 12506645
TI  - [Features of retinopathy of prematurity, progressing as "plus-disease"].
AB  - "Plus-disease" is a particular grave form of retinopathy of premature babies
      found in 7% of extremely premature and somatically loaded children. The following
      criteria are indicative of "plus-disease": location of pathological changes in
      the central zone of eye fundus (zone 1-2), marked vascular activity and
      hemorrhages in the center and on the periphery of the retina, pupil regidity,
      iris vasodilatation and fulminant (3 days-3 weeks) progression of the process
      from initial signs up to signs of extraretinal growth or exudative amotio retinae
      without forming premature stages typical for retinopathy (torus lines). Upon
      revealing the first signs of "plus-disease" ophthalmological examinations should
      be carried out with the interval of 2-3 days. To increase efficiency of
      preventive treatment it is recommended to use the combined procedure of cryo- and
      laser coagulation of avascular zones and a zone of vascular amostosis in
      appearance of extraretinal vascular growth, which makes it possible to arrest
      disease progression in 75% of cases.

PMID- 12506646
TI  - [Fulminant retinopathy of prematurity ("plus-disease"): incidence, risk factors,
      diagnostic criteria, and variations in course].
AB  - The authors examined 363 premature children with retinopathy. The fulminant form
      PH ("plus-disease") was found in 21.5% of cases. The authors determined risk
      factors of this PH form, diseases of mother during pregnancy, pregnancy
      pathology, infectious diseases of a new-born child with development of sepsis and
      pneumonia, grave hypoxic and ishemic affection of central nervous system with
      intraventricular hemorrhage of III-IV degree, and also exposure of children to
      artificial lung ventilation for more than 7 days and estimation by Apgar scale at
      less than 6 points. There were the following ophthalmologic prodromes of
      fulminant PH in early neonatal period: gray color of the optic disk, gray-yellow
      background of the eye fundus, coiled arteries and varicosity in retina center,
      coiled vessels on periphery of the eye fundus, total retina edema, multiple
      hemorrhages at the eye fundus, a wide avascular zone. There are the following
      absolute signs of this form: rigidity of the pupil, iris vasodilatation,
      localization of process in I-II zone of the eye fundus, a significant varicosity
      in center of eye fundus, a coiled way of central arteries, vasodilatation and
      sharply coiled vessels at the border with avascular zone, exudative and
      proliferative changes both at site of peripheric torus and at other sections of
      the eye fundus. To estimate process gravity, forecast and more pathogenetically
      substantiate treatment, the following forms of fulminant PH are singled out:
      hemorrhagic (11.5%), exudative (21.8%), neovascular (14.1%) and mixed (52.6%).

PMID- 12506647
TI  - [Comparative analysis of the efficacy of some methods of conservative treatment
      of accomodation spasms and myopia in children].
AB  - A study was carried out of short- and long-term results in treatment of
      accommodation spasms and myopia of mild and moderate degrees in children with
      equipment having different operating mechanism. 171 patients aged 6-15 years were
      examined (30 persons made up a control group). Electrostimulation, laser
      stimulation and treatment on "Ambliokor" equipment were used. It was found out
      that these procedures give a good immediate effect in treatment of accommodation
      spasm and myopia but 5-6 months later the obtained results deteriorated in 2/3 of
      children and therefore it is recommended to repeat the treatment in the above
      period. Using "Ambliokor" equipment provides the best short-term effect. The
      highest effectiveness of treatment was obtained in combined method comprising all
      three procedures which made it possible to reduce the rate of myopia progression
      2-fold and more compared with the similar index in the control group.

PMID- 12506648
TI  - [Indicators of general, cerebral, and regional hemodynamics in myopic
      schoolchildren aged 13-15 years].
AB  - 110 schoolchildren aged 13-15 years were examined. 24 of them had pseudomyopia
      and 6 patients myopia of various forms. A control group consisted of 38 children.
      Central hemodynamics was estimated by average dynamic pressure, cerebral
      hemodynamics--by rheoencephalography, regional hemodynamics--by dopplerography of
      the internal carotid and suprapubic arteries. It was found that with myopia
      progression, the average dynamic pressure positively comes down with reduction of
      reographic waves amplitude in rheogram. The blood flow rate in internal carotid
      and suprapubic arteries has no substantial impact on myopia course.
      Predisposition to arterial hypotension is a risk factor for myopia development
      and progression.

PMID- 12506649
TI  - [Immunogenetics of optic neuritis in children with multiple sclerosis].
AB  - The aim of the work was to study immunogenetic peculiarities of optic neuritis in
      children with MS. Using PCR-SSP technique genomic typing was performed on HLA
      DRB1 gene (chromosome 6p21) of 56 unrelated children with ON registered at least
      once in clinically verified MS. 264 adult MS patients and 328 healthy controls
      from the same stratum of population were also genotyped. A very strong
      correlation of MS with DR15 (DRB1*150 ... alleles) was observed in comparison
      with healthy cases in the above population. In 39 cases of children with ON and
      MS both parents were also genotyped and the rate of their DRB1 haplotypes
      transmitted (patients) and non-transmitted (control cases) to their sick children
      were compared in accordance with affected family-based (AFBAC) method. A very
      strong correlation of demielinating disease with DRB1*150 ... alleles was
      verified. Transmission/disequilibrium test (TDT) was carried out to analyze
      correlation in selected families consisting of one sick child and two parents at
      least one of whom was heterozygous for DR15. The difference observed in
      transmission from these parents of DR15 alleles and alternative DRB1 alleles was
      extremely great providing obvious evidence for correlation of DR15 (DRB1*150...)
      alleles and susceptibility of children to ON and MS.

PMID- 12506650
TI  - [Role of neurophysiological mechanisms in pathogenesis of optic nystagmus].
AB  - 54 children aged 6-14 years with optic nystagmus were examined. They were divided
      into two groups. Patients of group 1 (n = 26) had isolated nystagmus while 28
      patients of group 2 had nystagmus and concomitant ocular pathology. It was found
      out that visual deterioration was mainly related with the damage of the central
      part of visual analyzer. This was confirmed by alteration of contrast-frequency
      characteristics in the range of high frequencies, decline of amplitude and the
      alpha-rythm nebulosity in combination with high-amplitude fusiform oscillations.
      These data point to an impaired process in the formation of correlation between
      cortical areas and cerebral subcortical structures.

PMID- 12506651
TI  - [Phacoemulsification of traumatic cataracts].
AB  - A careful consideration was given to the results of surgical treatment of
      patients with traumatic cataracts complicated with concomitant pathology (corneal
      scars, anterior and posterior synechia, lens subdislocation, anterior and
      posterior crystalline capsule defects, etc.). In 107 cases phacoemulsification
      was done with other cases having lensectomy, intracapsular extraction or
      phacoaspiration of traumatic cataract. Indications and contraindications are
      specified for traumatic cataract phacoemulsification.

PMID- 12506652
TI  - [Ways of increasing effectiveness of eye prostheses].
AB  - The study of reasons of unsatisfactory eye prosthesis has shown that after
      insertion of cosmetic eye prosthesis into the conjunctival cavity in the majority
      of patients an inflammatory process develops which often goes on for several
      years. Discomfort and inflammation are mainly caused by a shift in acid-alkali
      balance in the conjunctival cavity, protein, fat and calcium deposits on the
      surface of prosthesis. The available agents of caring conjunctival cavity and
      prosthesis do not permit to fully clean prosthesis and to restore acid-alkali
      balance in cavity being equipped with prosthetic appliance. The authors offer new
      methods of taking care of prosthesis and conjunctival cavity making it possible
      to improve convenience of wearing eye prostheses, to disinfect them efficiently,
      clean them and prolong their service life.

PMID- 12506653
TI  - [Treatment of inflammatory conditions of the iris and ciliary body, accompanying
      fibrin exudation].
AB  - The paper presents a description of a new method for treatment of iris and
      ciliary body inflammation accompanied with fibrin exudation. We used low-level
      blue laser destroying a fibrin clot in its initial stage of formation. We also
      used herapin and ascorbic acid. In the absence of the greatest impact urokinase
      was additionally administered.

PMID- 12506654
TI  - [Preference for transscleral cryocoagulation of peripheral exudate in
      intermediate ubitis before traditional methods of treatment].
AB  - The term intermediate uveitis (IU) describes an anatomic distribution of ocular
      inflammation rather than a distinct clinicopathologic condition and includes pars
      planitis, chronic posterior cyclitis and peripheral uveitis. In the treatment of
      IU corticosteroids and cytostatic agents are of value but since the disease tends
      to have a long course they produce perminant side effects. Especially this
      therapy is undesirable in children. In some patients immunosuppressive therapy is
      not effective, particularly with peripheral neovascularization. Cryotherapy
      performed in 11 patients (16 eyes, 5 men, 6 women, mean age 22.9 +/- 8.1 years)
      with IU controlled inflammation during 13-37 months and prevented vitreous
      hemorrhage.

PMID- 12506655
TI  - [Cytokine status of patients with chlamydial conjunctivitis].
AB  - The study of cytokine status in 37 patients with chlamydial conjunctivitis
      revealed its noticeable alteration: increment of production of serum IL-16 and IL
      14 and IL-1 beta, IL-6 and TNF-alpha in the lacrymal fluid. The investigation of
      the cytokine status in patients with chlamydial conjunctivitis can be a valuable
      addition in the complex estimation of immunity to perform immunomodulating
      therapy.

PMID- 12506656
TI  - [Hyperplastic connective tissue syndrome in patients with high myopia].
AB  - A conventional ophthalmologic and special somatic examination was carried out in
      50 patients with myopia and 30 patients of the control group to determine
      hypermobility of joints by 9-point scale. Hypermobility of joints in patients
      with myopia was estimated at 5.95 points and in patients in the control group-
      2.7 points. All the patients with high myopia showed 12 various additional
      features of connective tissue hyperelasticity, on the average, with no more than
      4 such features in the control group. It is suggested that hereditary
      predisposition to hyperelasticity of connective tissue determines a particular
      inclination of the sclera to overextension. This plays a definite role in
      appearance and progress of axial myopia.

PMID- 12506657
TI  - [Use of a dual-component analytic method of rheoophthalmolography for assessing
      the functional status of vessels in the eye].
AB  - In order to eliminate subjectivity in interpretation, to increase research
      exactness and standardize all parameters of measuring a pulse blood flow, a two
      component analysis of rheoophthalmogram was employed which has been used in
      neurology since the 1980s. Characteristics of the eye blood flow were examined in
      the group of 62 healthy persons (30 young persons and 32 older persons). Modified
      rheoophthalmography makes it possible to reveal functional or organic change of
      uveal vessels to determine indications for vascular therapy and control its
      efficiency.

PMID- 12506658
TI  - [Effect of bacteriophage on the lipid peroxidation process and antioxidant
      protective enzymes in experimental uveitis].
AB  - Experimental uveitis features distinct hyperlipoperoxidation in damaged eye
      tissues, blood serum and the liver. The activity of antioxidant defense (AOD)
      enzymes decreases in tissues and blood of experimental animals whereas catalase
      compensatorily activates in hepatic tissue. Experimental therapy of uveitis with
      gentamycin and bacteriophage results in reducing hyperlipoperoxidation, increased
      activity of AOD enzymes but no complete normalization is observed. This
      manifested in preservation of inflammations to a certain degree.

PMID- 12506659
TI  - [Combined ocular form--proxofelin--in treating glaucoma].

PMID- 12506660
TI  - [Cycloplegic effectiveness of cyclopentolate and tropicamide preparations
      compared with atropinization].
AB  - To gain a comparative estimate of cycloplegic agents with mild effect vs
      conventional atropinization, a study was performed on refraction in 57 children
      after instillations of cyclopentolate and atropine and in 57 children after
      instillations of tropicamide and atropine. A difference was determined in
      refraction after instillation of cycloplegic agents with mild effect and
      atropine. It turned out that by depth of cycloplegic effect cyclopentolate is
      reaching that of atropine. Cyclopentolate can be used in initial study of
      refraction in children with hypermetropic and myopic refraction and in repeated
      studies of any refraction. Tropicamide is less effective cycloplegic agent than
      cyclopentolate and thus it can be used in initial studies of refraction in
      children with myopia and in repeat studies of refraction in children with myopia
      and hypermetropia and also in cases of intolerance of other cycloplegic agents.

PMID- 12506661
TI  - [Hippel-Lindau syndrome].

PMID- 12506662
TI  - [Transplant rejection: general questions of pathogenesis, diagnosis and
      treatment].

PMID- 12506663
TI  - [Role of lacrimal fluid, its quantitative and qualitative composition in
      development of "dry eye" syndrome].

PMID- 12506664
TI  - [Herman von Helmholz: life and scientific activities].

PMID- 12506665
TI  - [Linker histones: conformational changes and the role in the structural
      organization of chromatin].
AB  - Histones, linker histones of the H1 family, their postsyntetic modifications, DNA
      histone H1 interaction are reviewed. A question of protein change in
      spermatogenesis at the formation of inactive nucleus with high degree of DNA
      density is considered. Special attention was paid to sperm-specific histones of
      the H1 family of sperm cells. Their role in organization of high-order chromatin
      structure of sperm cells is discussed. Also, results of different studies on the
      structural organization of chromatin (nucleosomes, 30-nm fibers, chromatin loops
      and metaphase chromosomes) are discussed.

PMID- 12506666
TI  - [Morphofunctional parameters of nucleoli during development of the albumen gland
      polyploid cells in the snail Succinea lauta].
AB  - Ag-protein content, the total area and the number of nucleoli were estimated on
      AgNO3-methyl green stained squashed preparations of the albumen gland of Succinea
      lauta during polyploidization, differentiation and functioning of secretory
      cells. The investigation was made by means of morphometry and cytophotometry
      using the computer videoimage system. During the gland growth, the mean number of
      nucleoli increased from 1-2 in diploid (2c) nuclei to 3 in polyploid (16c-32c)
      nuclei, but commonly only one large nucleolus was formed in mature nuclei. As a
      whole, the area and Ag-protein content of nucleoli was changed proportionally to
      the gene dosage, but this dependence was not linear during several endocycles.
      Before 8c-level the coefficients of increase in each endocycle were more than 2
      (2.7-4.0), and these decreased to 1.5-1.0 during the following endocycles (8c-16c
      32c). The area of nucleoli increased more quickly than Ag-protein content in the
      course of endocycles of growing cells. On the contrary, a relative area of
      nucleoli decreased with the increase in ploidy levels in mature cells. This
      irregular dynamics reflects the influence of several factors of the nucleolar
      activity: endomitotic polyploidy (gene dosage effect), cell differentiation,
      inhibition of transcription, and its reactivation in mature cells. In addition,
      individual variations of nucleolar parameters in mature snails are associated
      with the rhythmical functioning of sexual system, and aging of animals.

PMID- 12506667
TI  - [Morphofunctional basis of neurosecretory cell plasticity].
AB  - Mass accumulation and storage of neurosecretory products are typical only for
      nonapeptidergic elements, as it has been shown by our study of the structure and
      function in neurosecretory cells of different nature. All liberinergic,
      statinergic and monoaminergic neurosecretory cells keep constancy in the state of
      high functional activity of extrusive processes at normal conditions. Morpho
      functional features of these elements principally differ from those of
      nonapeptidergic neurosecretory cells, which are characterized by remarkable
      secretory cycles. The extremely large size of elementary secretory granules,
      maximum development of the Herring bodies, various modes of secretion, secretory
      and extrusive cycles in neurosecretory function, and massive accumulation of
      neurosecretory granules occurring in neurosecretory terminals finally, all these
      characters are considered to be the primary features of a high plasticity of the
      nonapeptidergic neurosecretory cell. A high reactivity of nonapeptidergic
      neurosecretory cells has been demonstrated here by the quantitative
      ultrastructural research of the dynamics of functional activity of neurosecretory
      terminals at both experimental and physiological stressful states. The highest
      plasticity of nonapeptidergic neurosecretory cells compared to all other
      neurosecretory cell types may be provided by their ability to restore the initial
      law level of functional activity, referred to as "functional reversion".

PMID- 12506668
TI  - [Quantitative investigation of reproduction of condensed chromatin of sex
      chromosomes during trophoblast cell polyploidization and endoreduplication in the
      East European field vole Microtus rossiaemeridionalis].
AB  - Simultaneous measurement of DNA content in cell nuclei and condensed chromatin
      bodies formed by heterochromatized regions of sex chromosomes (gonosomal
      chromatin bodies, GCB) has been performed in two trophoblast cell populations of
      the East-european field vole Microtus rossiaemeridionalis, namely in the
      proliferative population of trophoblast cells of the junctional zone of placenta
      and in the secondary giant trophoblast cells. One or two gonosomal chromatin
      bodies have been observed in trophoblast cell nuclei of all embryos studied
      (perhaps both male and female), In the proliferative trophoblast cell population,
      characterized by low ploidy levels (2c-16c), and in the highly polyploid
      population of secondary giant trophoblast cells (16c-256c), the total DNA content
      in GCB increased proportionally to the ploidy level. In separate bodies, the DNA
      content rose also in direct proportion with the ploidy level seen in the nuclei
      with both one and two GCBs in the two trophoblast cell populations. A certain
      increase in percentage of the nuclei with 2-3 GCBs was shown in the nuclei of the
      junctional zone of placenta; this may be accounted for by genome multiplication
      via uncompleted mitoses. In the secondary giant trophoblast cell nuclei (16c
      256c), the number of GCBs did not exceed 2, and the share of nuclei with two GCBs
      did not increase, thus suggesting the polytene nature of sex chromosome in these
      cells. At different poloidy levels, the ratio of DNA content in the nucleus to
      the total DNA content in GCB did not change significantly giving evidence of a
      regular replication of sex chromosomes in each cycle of genome reproduction. In
      all classes of ploidy, the mean total DNA content in trophoblast cell nuclei with
      single heterochromatic body was less than in the nuclei with two and more GCBs.
      This may indicate that a single GCB in many cases does not derive from the fusion
      of two GCBs. To put it another way, in the nuclei with one GCB and in those with
      two or more GCBs, different chromosome regions may undergo heterochromatization.
      The regularities observed here are, most probably, associated with the
      peculiarities in the structure of X- and Y-chromosomes in a range of species of
      Microtus (M. agrestis, M. rossiaemeridionalis, M. transcaspicus). As a result,
      gonosomal chromatin bodies may include large blocks of both constitutive
      heterochromatin of X- and Y-chromosomes (in male and female embryos) and
      inactivated euchromatin of "lyonized" X-chromosome in female embryos. Therefore
      the presence of two or more GCBs in trophoblast cells of M. rossiaemeridionalis
      may be accounted for by both polyploidy and functional state of the nucleus, in
      which gonosomal constitutive heterochromatin and inactivated euchromatin form two
      large chromocenters rather than one. The differences in DNA content in GCBs in
      the nuclei with one and two GCBs seem to be an indirect indication that the two
      chromocenters may be formed by two different gonosomes, with the extent of their
      heterochromatization being higher than that in the nuclei with one GCB. GCBs in
      the trophoblast cells of M. rossiaemeridionalis are observed not only at the
      early developmental stages, as it was observed in rat at the first half of
      pregnancy (Zybina and Mosjan, 1967), but also at the later stages, up to the 17th
      day of gestation. At these stages, the nuclei with non-classical polytene
      chromosomes rearrange to those with a great number of endochromosomes, probably
      because of disintegration of chromosomes into oligotene fibrils. However, it does
      not seem unlikely that this process may involve heterochromatized gonosomal
      bodies, since only one or two large GCBs can be seen in the nuclei as before. The
      presence of prominent blocks of constitutive heterochromatin seems to favor a
      closer association of sister chromatids in polytene chromosomes, which prevents
      their dissociation into endochromosomes with the result that polyteny of sex
      chromosomes in the field vole trophoblast is probably retained during a longer
      period of embryonic development.

PMID- 12506669
TI  - [Effect of melanins from black yeast fungi on cultured human cells. I.
      Proliferation of keratinocytes and fibroblasts].
AB  - Results of screening of the influence exerted by yeast black melanin on the
      proliferation of human skin keratinocytes and embryonic fibroblasts are
      presented. The optimal concentration of the investigated melanins was found to be
      within 0.005 and 0.0001 mg/ml. 17 samples of DHN-melanin from black yeast and 2
      commercial samples of [symbol: see text]OPA-melanin (natural and synthetic) were
      investigated. It was established that keratinocyte proliferation was inhibited by
      3 black yeast melanin samples; the influence of other 14 samples was the same as
      in the control. Keratinocyte proliferation was stimulated only by a commercial
      sample of natural [symbol: see text]OPA-melanin at concentration 0.005 mg/ml. The
      synthetic melanin at concentrations 0.005 and 0.001 mg/ml inhibited keratinocyte
      proliferation. Of the 17 investigated black yeast melanin samples, only one
      sample stimulated fibroblast proliferation at concentration 0.005 mg/ml. Three
      other samples inhibited the proliferation; of these one sample did it at all used
      concentrations, and two samples at concentration 0.0001 mg/ml. The rest 13
      samples of black yeast DHN-melanins and the synthetic [symbol: see text]OPA
      melanin did not differ in either action from the control.

PMID- 12506670
TI  - [Effect of melanins from black yeast fungi on cultured human cells. II.
      Differentiation of keratinocytes in vitro].
AB  - Data on the influence of the black yeast melanin (3 samples) on the in vitro
      differentiation of human keratinocytes are presented. The effect of melanins was
      estimated by the morphological state of keratinocytes using electron microscopy.
      The obtained differences in the state of the formed multilayer keratinocyte
      sheets depended on the melanin sample.

PMID- 12506671
TI  - [Various effects of laminin-1 and laminin-2/4 on adhesion and migration of
      cultured human keratinocytes].
AB  - The cell-matrix interaction is one of the factors defining the cell behavior in
      normal and wounded tissues. To determine the function of laminin-2/4, one of
      components of the skin basement membrane in the process of reepithelization, we
      studied its interaction with human keratinocytes. The adhesive properties of
      laminin-2/4 and its effect on keratinocytes migration in vitro were analysed. For
      comparison with our present investigation, we used the earlier studied laminin-1
      from EHS mouse sarcoma. Laminin-2/4 appeared to be a good substrate for human
      keratinocytes, and this correlates with a greater number of cell surface
      receptors compared with laminin-1. Laminin-2/4 alone does not stimulate
      keratinocyte migration, but, in contrast to laminin-1, supports EGF-mediated
      migration. The obtained results give an insight into the function of laminin-2/4
      in normal skin and during wound healing.

PMID- 12506672
TI  - [Effect of monokines induced by Yersinia pestis EV on the functional activity of
      neutrophils during development of antiplague immunity].
AB  - A study was made of the Yersinia pestis EV induced monokine complex influence on
      neutrophil (Nph) functional activity in the course of antiplague immunity
      formation. The obtained monokines essentially enhance Nph killing, chemotactic
      activities and Fc-receptor expression, and stimulate lysosome membrane
      labilization of these cells. The helper effect of the Y. pestis EV induced
      monokines on Nph functional activity is more pronounced during the secondary
      immune response, than in the course of the primary one.

PMID- 12506673
TI  - Hsp70 family proteins seem to facilitate allo- and xenotransplantation in the rat
      brain.
AB  - Drosophila neuroectodermal embryonic cells were transplanted into the occipital
      brain region of adult rats. The first series of experiments used a transgenic
      strain expressing lacZ to detect the presence of Drosophila cells. The second
      series used a strain carrying a is lethal (ts403) in the X chromosome; this
      mutation strongly inhibits the synthesis of heat shock proteins (hsps) and their
      transport into the nuclei. Immunostaining reveals a strong induction of hsp70 in
      the xenografts in the first series of experiments, in which no glial scar was
      detectable. By contrast, where the ts mutation was xenotransplanted, the
      condition of xenografts was worse, and a glial scar was readily evident between
      the xenograft and host tissue.

PMID- 12506674
TI  - [Effect of an vacuolar proton pump inhibitor bafilomycin A1 on the intracellular
      processing of markers for receptor-mediated and liquid phase endocytosis].
AB  - By means of subcellular fractionation in density Percoll gradients,
      immunoblotting and immunofluorescense, the effect of BafA1 on endocytosis of EGF
      receptor complexes and horse radish peroxidase (HRP) in A431, HER14 and HC11 cell
      lines was studied. It was shown that the pretreatment of all used cell lines with
      BafA1 completely inhibited EGF degradation, but did not interfere with the
      delivery of significant portion of EGF-receptor complexes to late endosomes and
      lysosomes and transition of the receptor to juxtranuclear region. At the same
      time, BafA1 was found to dramatically inhibit the delivery of fluid phase marker
      HRP to late endosomes of A431 cells. The BafA1 effect on endocytosis of high
      concentrations of EGF was similar to that on HRP endocytosis. Regulatory
      mechanisms of early-to-late endosomal compartment transition are discussed.

PMID- 12506675
TI  - ["Sepsis"].

PMID- 12506676
TI  - Innate immune sensing of microbial infection: the mechanism and the therapeutic
      challenge.
AB  - Studies of sepsis conducted over the century have led to an understanding of many
      of the molecular events that take place during a severe infection. But what are
      the first events? Very recent genetic analyses have provided an answer to this
      question. Genetic studies have disclosed that bacterial endotoxin is sensed
      through a solitary biochemical pathway. At the heart of this pathway is the Toll
      like receptor 4 (TLR4): one member of an ancient receptor family dedicated to the
      detection of infectious organisms. Most and perhaps all of the untoward effects
      of infection are initiated by the TLRs, ten of which are represented in humans.
      At the same time, it is known that TLRs are required to sense infection at its
      earliest stages, and thereby defeat it. The means to block TLR signal
      transduction is now at hand. Will this do good or harm?

PMID- 12506677
TI  - Advances in research of the inflammatory response: the importance of toll-like
      receptors.
AB  - The innate immune system provides the first line of defence against invading
      pathogens. Cells that mediate the innate immune response express a variety of
      receptors that permit recognition of pathogen-associated motifs, subsequently
      resulting in a cascade of responses that initiates inflammation. Recently, the
      members of the Toll-like receptor family (TLR) have emerged as key receptors
      responsible not only for the detection of a variety of microbial cell-wall
      components and bacterial DNA but also for the initiation of signal transduction
      events eventually leading to the production of various proinflammatory mediators.

PMID- 12506678
TI  - [Corticosteroids in septic shock].
AB  - Adequate adrenocortical function is essential to survive critical illness. Most
      critically ill patients display an elevated plasma Cortisol level, reflecting
      activation of the pituitary-adrenal axis, which is considered to be a homeostatic
      adaptation. In the setting of critical illness, the failure of an appropriate
      neuroendocrine response can lead to the picture of vasopressor-dependent
      refractory hypotension. In randomised trials with patients in septic shock, a
      more rapid haemodynamic recovery was obtained with physiological doses of
      hydrocortisone than with placebo. The observed haemodynamic response following
      hydrocortisone administration supports the concept of relative adrenal
      insufficiency. Causes of this relative adrenal insufficiency are a dysfunction of
      the hypothalamic-pituitary-adrenal axis and/or Cortisol resistance. There is
      increasing evidence that Cortisol physiology and regulation are substantially
      altered in the course of septic shock. Several controlled studies have shown that
      stress doses of hydrocortisone given in patients with septic shock reduce the
      time to shock reversal and decrease mortality. A multicenter large-scale trial
      (CORTICUS) is on the way investigating the benefit of stress doses of
      hydrocortisone on the mortality of septic shock. In this review glucocorticoid
      physiology and regulation during septic shock and the effects of hydrocortison
      administration in the course of septic shock are being discussed.

PMID- 12506679
TI  - [Pathophysiology and therapy of sepsis-associated coagulation disorders].
AB  - Sepsis and septic shock are very complex and dynamic clinical syndromes. A
      systemic response to an infection or other triggers can induce a cascade
      consisting of toxins--leukocytes--cytokines--mediators of inflammation-
      endothelial cell dysfunction--activation of blood coagulation--intravascular
      fibrin deposition--alteration of microcirculation, resulting in a damage of
      organs. Multi organ failure and sepsis are therefore tightly connected. The
      associated disturbances of blood coagulation range between a simple activation of
      coagulation with a transient increase of activation markers (i.e. D-dimer),
      similar to an acute-phase reaction and full blown disseminated intravascular
      coagulation with consumption coagulopathy. This article summarizes these
      pathophysiological mechanisms, shows available diagnostic tools and differential
      diagnoses, and discusses therapeutic options for sepsis and multi organ failure.

PMID- 12506680
TI  - [Sepsis in hemato-oncologic patients].
AB  - The general approach regarding the treatment of sepsis in patients with
      oncological or haematological malignancies does not differ significantly from
      that in immunocompetent individuals, however, there are several specialities. The
      main causes of severe infections in cancer patients include deranged cellular or
      humoral immunity due to the underlying disease, severe neutropenia as a
      consequence of cytostatic regimens, lesions of the mucosal barriers due to
      adverse effects of antineoplastic agents, and violations of the integument by
      therapeutic interventions. Due to the impaired host defense, life threatening
      infections can occur more often in these patients, thereby limiting the benefits
      of antineoplastic therapy. On this account precise and intensive therapy has to
      be initiated in the early stages of sepsis. In the following, we will not
      primarily focus on sepsis specific treatment modalities, but merely try to
      elucidate in more detail the pathomechanisms and special features with regard to
      infectious complications and specific treatment.

PMID- 12506681
TI  - [Visual documentation of the stability of intravenous solutions of omeprazole
      (Losec) and pantoprazole (Pantoloc)].
AB  - Patients with complications of peptic ulcers, high grade reflux oesophagitis, or
      Zollinger Ellison syndrome need a sufficient permanent acid suppression. In
      appropriate indications they receive proton pump inhibitors (PPI) intravenously
      or via perfusion over a longer period, if an oral application is not possible.
      PPIs are prodrugs, which should be converted into the active principle in the
      acidic canaliculus at pH 1 of the parietal cell. Otherwise they would be
      activated prematurely. Immediate chemical degradation causes discolouration. Aim
      of the study was to compare pH stabilities of the intravenous formulations of
      Omeprazole (different solutions for infusion and injection) and Pantoprazole (one
      solution for injection and infusion). The solutions prepared accordingly to the
      official instructions, were exposed to four different light conditions. Both
      manufacturers (AstraZeneca Osterreich GmbH, Byk Osterreich Pharma Ges.m.b.H.)
      state reference solutions for acceptable discolouration. Those were prepared
      according to the European Pharmacopeia. Discolouration of solutions were
      evaluated as criterion for stability of the PPI prodrugs. If change of colour is
      at least of the extent of the corresponding reference solution, further use is no
      longer permitted. Optical alterations under different light conditions were
      compared and documented photographically with standardized illumination.
      Intensity and spectral composition of light as well as temperature had only minor
      influence on discolouration as measure of degradation of the prodrugs. Both
      formulations for injection fulfill the specifications for pH stability within the
      stated time frames mentioned in the summaries of product characteristics (SPC).
      Comparing both products, after a short period (1 hour) Omeprazole injectable
      formulation showed a substantial optical discolouration. After 6 hours these
      changes were more intense than the reference solution BG5 allows. Pantoprazole
      showed optical alteration to a notable later time point. After 24 hours
      discolouration reached the reference colour B6. Injectable formulation of
      Pantoprazole is about three times more stable than that of Omeprazole. Infusion
      solution of Omeprazole shows no optical alteration within the stated time frame
      due to high dilution and pH value. Assuming that 100 ml of the infusion solution
      contains 40 mg Omeprazole. It takes 5 hours for the volume to be infused at a
      dose regimen of 8 mg/h. Therefor 5 x 100 ml/24 h are needed.

PMID- 12506682
TI  - [Sports-induced infections--an overview].
AB  - Sportive activities are playing an increasing role for the spare time in our
      society. Subsequently, practicing of various kinds of sport can lead to direct
      and indirect exposures to and transmission of microorganisms between athletes and
      also passive observers. As a result, different microbial pathogens can be
      transmitted and might lead predominantly to cutaneous or mucosal infections.
      These include both bacteria--Staphylococcus aureus, streptococci and gram
      negative bacteria, like Pseudomonas, viruses--herpes simplex virus, human
      papilloma virus--and, last but not least, also dermatophytes--e.g. Trichophyton
      tonsurans as particular pathogenic agent of tinea gladiatorum. Beside single
      cases of infections outbreaks through various virus-, bacteria- and dermatophytes
      induced infections might happen and have indeed been reported. Surprisingly,
      there is only limited knowledge among physicians concerning sport-induced
      infections. Therefore, sport-induced infections are reviewed giving details about
      their route of transmission. Awareness of these infections might facilitate
      implementation of early treatment and preventive measures.

PMID- 12506683
TI  - [Therapy refractory depression: symptom improvement after antidepressant and
      methylphenidate combination therapy].
AB  - In common, depressive disorders are treated with various antidepressants, the
      number of which is enormously increasing. Nevertheless, in some cases therapy
      resistance is observed. In these cases, neuroleptics are used as an alternative.
      Methylphenidate is effective for the treatment of ADHD and narkolepsia. But there
      are also studies, reporting an effect of methylphenidate in depressive disorders.
      We did not find any report about the efficiency of a combination of
      antidepressants and methylphenidate. We report a 32 year old "therapy resistant"
      depressive female. Monotherapy with antidepressants and methylphenidate was
      ineffective. Finally, a combination of antidepressants and methylphenidate was
      effective and lowered the HAMD-Score significantly. A combination of
      antidepressants and methylphenidate seems to be an effective new option for the
      treatment of "therapy resistant" depressions.

PMID- 12506684
TI  - [Aerobic physical training in a breast cancer patient with inflammatory
      recurrence].
AB  - Aerobic exercise has positive effects on physical performance and illness-related
      quality of life of cancer patients. However reports of advanced cancer patients
      who exercise are rare in medical literature. A 38-year-old female patient
      suffering from breast cancer performed an aerobic exercise program during
      adjuvant chemotherapy (cycle ergometry, 3x/w). After the diagnosis of relapsed
      inflammatory breast cancer, oncological treatment was changed to radiation
      therapy to reduce tumour mass. The patient continued the exercise program until
      palliative mastectomy. Her compliance was excellent. Despite the underlying
      progressive disease, endurance performance improved substantially. These findings
      were supported by a subjective score (Grimby). Evaluation of quality of life (SF
      36, EORTC-QLQ-C30) revealed improvements of emotional wellbeing, emotional role,
      vitality and physical functioning, but increasing pain. The patient reported
      benefit due to increased psychological, social and physical wellbeing. This case
      report demonstrates feasibility and benefits of aerobic exercise for a patient
      with advanced breast cancer undergoing palliative treatment.

PMID- 12506685
TI  - Drugs of abuse. Introduction.

PMID- 12506686
TI  - The temporal sequence of changes in gene expression by drugs of abuse.

PMID- 12506687
TI  - Effects of psychomotor stimulants on glutamate receptor expression.

PMID- 12506688
TI  - Adult neural stem/progenitor cells in the forebrain. Implications for
      psychostimulant dependence and medication.

PMID- 12506689
TI  - Neuroprotective effect of naloxone in inflammation-mediated dopaminergic
      neurodegeneration. Dissociation from the involvement of opioid receptors.

PMID- 12506690
TI  - Neuropharmacology and neurotoxicity of 3,4-methylenedioxymethamphetamine.
AB  - The existing data indicate that MDMA produces long-term deficits in markers of 5
      HT axon terminals in the rodent brain. Increased cleavage of the cytoskeletal
      protein tau, impairment of axonal transport, and functional consequences
      associated with a 5-HT depleting regimen of MDMA support the view that MDMA
      induces structural brain damage, that is, axonal degeneration. A confluence of
      oxidative stress and bioenergetic stress induced by MDMA is hypothesized to
      underlie the process of MDMA neurotoxicity (Fig. 3). The actions of MDMA on the 5
      HT transporter to promote free radical formation and/or intracellular calcium may
      synergize with MDMA-induced disturbances in cellular energetics and hyperthermia
      to effect selective toxicity to 5-HT axon terminals.

PMID- 12506691
TI  - Learning and memory mechanisms involved in compulsive drug use and relapse.

PMID- 12506692
TI  - From drugs of abuse to parkinsonism. The MPTP mouse model of Parkinson's disease.

PMID- 12506693
TI  - In situ hybridization with isotopic riboprobes for detection of striatal
      neuropeptide mRNA expression after dopamine stimulant administration.

PMID- 12506694
TI  - Combining in situ hybridization with retrograde tracing and immunohistochemistry
      for phenotypic characterization of individual neurons.

PMID- 12506695
TI  - Analysis of mRNA expression using double in situ hybridization labeling with
      isotopic and nonisotopic probes.

PMID- 12506696
TI  - Quantification of mRNA in neuronal tissue by northern analysis.

PMID- 12506697
TI  - Analysis of gene expression in striatal tissue by multiprobe RNase protection
      assay.

PMID- 12506698
TI  - Analysis of mRNA expression in striatal tissue by differential display polymerase
      chain reaction.

PMID- 12506699
TI  - Semiquantitative real-time PCR for analysis of mRNA levels.

PMID- 12506700
TI  - Application of TaqMan RT-PCR for real-time semiquantitative analysis of gene
      expression in the striatum.

PMID- 12506701
TI  - Systematic screening of gene expression using a cDNA macroarray.

PMID- 12506702
TI  - Quantification of protein in brain tissue by western immunoblot analysis.

PMID- 12506703
TI  - Immunohistochemical and immunocytochemical detection of phosphoproteins in
      striatal neurons.

PMID- 12506704
TI  - Analysis of protein expression in brain tissue by ELISA.

PMID- 12506705
TI  - Dopamine receptor binding and quantitative autoradiographic study.

PMID- 12506706
TI  - Analysis of DNA-binding activity in neuronal tissue with the electrophoretic
      mobility-shift assay.

PMID- 12506707
TI  - Viral-mediated gene transfer to study the behavioral correlates of CREB function
      in the nucleus accumbens of rats.

PMID- 12506708
TI  - Generating gene knockout mice for studying mechanisms underlying drug addiction.

PMID- 12506709
TI  - Antisense approaches in analyzing the functional role of proteins in the central
      nervous system.

PMID- 12506710
TI  - Primary striatal neuronal culture.

PMID- 12506711
TI  - Primary rat mesencephalic neuron-glia, neuron-enriched, microglia-enriched, and
      astroglia-enriched cultures.

PMID- 12506712
TI  - Primary culture of adult neural progenitors.

PMID- 12506713
TI  - Organotypic culture of developing striatum. Pharmacological induction of gene
      expression.

PMID- 12506714
TI  - Microdialysis coupled with electrochemical detection. A way to investigate brain
      monoamine role in freely moving animals.

PMID- 12506715
TI  - HPLC/EC detection and quantification of acetylcholine in dialysates.

PMID- 12506716
TI  - Real-time measurements of phasic changes in extracellular dopamine concentration
      in freely moving rats by fast-scan cyclic voltammetry.

PMID- 12506717
TI  - Measurement of dopamine uptake in neuronal cells and tissues.

PMID- 12506718
TI  - Laboratory analysis of behavioral effects of drugs of abuse in rodents.

PMID- 12506719
TI  - Conditioned place preference. A simple method for investigating reinforcing
      properties in laboratory animals.

PMID- 12506720
TI  - Detection of cell proliferation and cell fate in adult CNS using BrdU double
      label immunohistochemistry.

PMID- 12506721
TI  - Threshold conditions for infection persistence in complex host-vectors
      interactions.
AB  - As classically defined by Macdonald in the early 1950s, for the case of diseases
      with one vector and one host, the Basic Reproduction Number, R0, is defined as
      the number of secondary infections caused by a single infective of the same type
      (vector or host) during its infectiousness period in an entirely susceptible
      population. In the case of a disease which has one vector and one host, it is
      easy to show that R0 coincides with the threshold for the establishment of an
      endemic state: if R0 > 1 (< 1), the disease can invade (cannot invade) the host
      population. In this paper we examine various epidemic situations in which there
      are more than one vector and/or host. We show that in those more complex systems
      it is not possible to deduce a single R0 but rather a threshold for infection
      persistence which is a composite of several quantities closely related to the
      classical expression of R0. Another definition of R0 given by Diekmann,
      Heesterbeek and Metz, and denoted in this paper R0NGO is discussed and applied as
      an alternative to calculate the thresholds for infection establishment.

PMID- 12506722
TI  - Roles of positive and negative feedback in biological systems.
AB  - We discuss the influence of positive and negative feedback on the stability of a
      system, which is not clear-cut, and involves complex, mathematical problems. We
      show in particular that positive feedback can have a stabilising effect on some
      systems. We also point out the role that positive feedback plays in the digital
      treatment of signals required by cellular signalling, drawing on analogies from
      electronics, and the role that negative feedback plays in making a system robust
      against alteration of its parameters. Both positive and negative feedback can be
      seen as important enhancers of the properties of biological systems.

PMID- 12506723
TI  - [Hydrous and photosynthetic adaptations of common and durum wheat to saline
      stress].
AB  - Seven varieties of bred wheat and seven varieties of durum wheat were cultivated
      in three different sites from the area of Errachidia (southeastern Morocco).
      These sites differ by the degree of salinity in the irrigation water. Results
      obtained showed that the reduction in leaf area is the principal strategy that
      makes it possible to attenuate the effects of the reduction in the availability
      of water under saline stress. Bread wheat, which limited the reduction in the
      leaf area, with the risk to undergo some hydrous problems, seems to better
      preserve its photosynthetic potentialities and grain productivity.

PMID- 12506724
TI  - Interference of activated factor VII in apoptosis of erytholeukemic K562 cells.
AB  - Coagulation factor VIIa (FVIIa) is a key protease initiating the coagulation
      cascade in the presence of its receptor, tissue factor (TF). FVIIa elicits
      several cellular responses, probably involving other receptors(s) than TF. This
      study investigates the implication of recombinant FVIIa on the apoptosis of K562
      erythroleukemia cells. These cells undergo apoptosis when induced to
      differentiate towards the erythroid lineage by hemin. They do not express TF, but
      can be transfected to do so. FVIIa treatment significantly reduced the degree of
      hemin-induced apoptosis in K562 cells, but not in TF+ derived transfectants.
      Induction of apoptosis by hemin also elicited decrease in intracellular Ca2+
      concentration ([Ca2+]i), but FVIIa restored this [Ca2+]i close to that of non
      treated cells. These results suggest that FVIIa acts via a TF-independent pathway
      to counteract apoptosis by a mechanism involving its Gla domain and linked to the
      maintenance of Ca2+ homeostasis in K562 cells.

PMID- 12506725
TI  - Atherina punctata and Atherina lagunae (Pisces, Atherinidae), new species found
      in the Mediterranean sea. 2. Molecular investigations of three Atherinid species.
AB  - On the basis of morphoanatomical parameters, the sand smelt species (Atherina
      boyeri Risso, 1810) is viewed as a highly polymorphic complex. In this study,
      intraspecific sequence variation in a portion of the cytochrome b gene was
      examined in 88 individuals from Tunisia and France. The correlation between the
      results of statistical analysis of the sequence data using a variety of tree
      building algorithms and morphoanatomical analyses demonstrated the subdivision
      into three putative species: A. boyeri, which only includes non-punctuated
      fishes, A. punctata, which corresponds to punctuated fishes and A. lagunae, which
      corresponds to atherines living in lagoons.

PMID- 12506726
TI  - [Populus nigra L. in the Garonne valley: legacy of the past and present
      constraints].
AB  - This study used documents from archives and historical maps to follow the
      simultaneous change of the riparian woodlands (where Populus nigra is dominant)
      and the poplar plantations. Results showed that the riparian woodland decreased
      by 81% over the two last centuries. Each period was characterised by the
      dominance of only a few number of clones. The risk of introgression due to the
      massive presence of such a restricted genetic material around P. nigra was
      discussed. The impact of river management on poplar regeneration was examined as
      well.

PMID- 12506727
TI  - New genus and species of brachyuran crab from the southern East Pacific Rise
      (Crustacea Decapoda Brachyura Bythograeidae).
AB  - A new genus and species of a brachyuran crab, Allograea tomentosa n. gen. and n.
      sp., of the family Bythograeidae, collected at a hydrothermal vent locality south
      of the Easter Microplate (31 degrees 09'S) on the southern East Pacific Rise, is
      described. The genus Allograea is distinguished by lacking modifications of the
      fronto-orbital region, and by the absence of coloured fields and setal patches on
      the carapace and chelipeds. The body and legs are smooth but densely covered by a
      brown tomentum, the eyestalks are not reduced, but the cornea is unfaceted and
      unpigmented. Comparison of mitochondrial DNA sequences among all known
      bythograeid genera confirms the novelty of this taxon.

PMID- 12506728
TI  - [The attraction of silk: base of group cohesion and collective behavior in social
      spiders].
AB  - Social spiders differ from social insects by the production and the use of silk
      to build irregular webs. This silk prevents dispersion of the individuals and
      ensures the group cohesion during swarming and collective displacements, playing
      a part similar to tracks of pheromones in ants. A social spider Anelosimus
      eximius is attracted by conspecific silk and does not show any discrimination
      relative to its origin, excluding any group closure. The quantity of silk and the
      state of satiety of the individual modulate this attraction, and might explain
      how the spider society adapts the size of the web to its nutritional needs.

PMID- 12506729
TI  - Reimbursement issues loom for Medicare+Choice in 2003.

PMID- 12506730
TI  - Overexposure hurts health system despite higher cap rates.

PMID- 12506731
TI  - Control your exposure for costs of injectables, biologics.

PMID- 12506732
TI  - Physician practice cost data offer benchmarks for small, large groups.

PMID- 12506733
TI  - No end in sight for double digit health care cost hikes.

PMID- 12506734
TI  - [Conference: Electrostimulation 2002].

PMID- 12506735
TI  - [Equipment for electrostimulation of the nervous and muscular systems:
      investigations, design, and application].
AB  - The paper considers the history, the state-of-the-art, and prospects for
      development of electrostimulation and appropriate equipment. The results of
      Russian studies and developments in this field are presented.

PMID- 12506736
TI  - [Interventional and surgical arrhythmology: state of the art, problems and
      prospects for development].
AB  - The paper considers the state-of-the-art, problems, and prospects for development
      of interventional and surgical arrhythmology in Russia, which is a
      multidisciplinary specialty which integrates present-day achievements of medicine
      and new technologies in the diagnosis and treatment of cardiac arrhythmias.

PMID- 12506737
TI  - [History of development of manufacture of implanted pacemakers: plans and
      reality].
AB  - The paper deals with the history of design and development of implanted
      pacemakers, emphasis is also laid on electric neuromyostimulators. Present-day
      problems and prospects in this area are touched upon.

PMID- 12506738
TI  - [A program-controlled electromyostimulation system in the treatment of rectal
      diseases].
AB  - The paper presents data on a programme-controlled system used to treat functional
      diseases of the large bowel and the rectal sphincter apparatus and based on a
      combined stimulation of perineal muscles and intestinal smooth ones by the
      biological feedback method.

PMID- 12506739
TI  - [Combined treatment of congenital blepharoptosis in children and adolescents].
AB  - The paper deals with a complex procedure for rehabilitation of children with
      congenital blepharoptosis, which includes the multilevelled impact on the
      concerned central and peripheral links of the neuromuscular apparatus by using
      magnetic laser therapy and electrostimulation.

PMID- 12506740
TI  - [Mesodiencephalic modulation (transcranial electrostimulation of the brain) in
      neurology and psychiatry].
AB  - The paper outlines the results of mesodiencephalic modulation (MDM) as therapy in
      adults and children with neurological and mental diseases in the out- and
      inpatient setting. MDM is a method of transcranial electric therapy that
      normalizes the performance of the hypothalamohypophyseal and opioid systems of
      the brain, which ultimately improves the body's adaptive response in disease.

PMID- 12506741
TI  - [Assurance of functional safety of electronics in cardiac pacemakers].
AB  - The paper considers the causes of failure of electronics in pacemakers and
      actions made to reduce the likelihood of malfunction.

PMID- 12506742
TI  - [Some possibilities of using multi-program electro-stimulators of the functional
      series Omnistim].
AB  - The paper presents data on multiprogram microprocess neuromyostimulators of the
      series Omnistim wherein the time course of changes in the parameters of action is
      determined by the pattern of changes in the lability of stimulated structures,
      such as skeletal muscles, smooth muscle organs, sensory conductors, etc. A great
      deal of programmes (over 100) open up a wide field uses for these stimulators and
      provide their high efficiency.

PMID- 12506743
TI  - [Prerequisites to the use of multichannel programmed muscle electrostimulation in
      patients with infantile cerebral palsy].
AB  - The paper deals with the use of multichannel programmed electrostimulation of
      muscles or artificial correction of movements to treat patients with infantile
      cerebral paralysis. This electrostimulation is a highly effective technique for
      correction of a pathological human motor stereotype and serves to consolidate the
      physiological movement patterns simulated during treatment sessions.

PMID- 12506744
TI  - [Electrostimulation and magnetic therapy in the treatment of accommodation cramp
      and in the prevention of progressive myopia in children and adolescents].
AB  - The paper presents a procedure and results of use of electrostimulation, magnetic
      therapy, and electrophoresis during treatment for accommodation cramp and in the
      prevention of myopia in children and adolescents. Data that characterize the
      dynamics and stability of achieved results are given.

PMID- 12506745
TI  - [Complex biotechnical feedback in electrostimulation systems].
AB  - Basic principles in design of electrostimulating equipment with complex
      biotechnical coupling combining biotechnical feedback and biological feedback are
      formulated. Realization of these principles in one system leads to qualitatively
      new capacities of enhancing the efficiency of implemented rehabilitative
      measures, which is the basis of the designed multichannel electromyostimulation
      device MYOS having a complex biotechnical feedback, which is used to treat a
      number of central and peripheral motor disorders (paralyses, pareses), to correct
      movements, to learn motor skills during training, etc.

PMID- 12506746
TI  - [Spinal cord stepping electrostimulation as a method for recovery of locomotor
      activity in vertebrogenic myelopathies].
AB  - The paper summarizes accumulated data on the parameters effective in calling
      alternate leg stepping and the areas of application of spinal cord
      electrostimulation, as well as the results of its application to restore
      locomotor capacities (tetra- and bipedal walking) of paralyzed patients.

PMID- 12506747
TI  - [Noninvasive transcranial electrostimulation of endorphin structures of the brain
      as a reparation activator: experimental and clinical parallels].
AB  - The authors evaluated the capacities of transcranial electrostimulation and the
      specific features of its impact on reparative regeneration of damaged tissues of
      different types, such as the dermal and gastroduodenal epithelium, hepatic cells,
      connective tissue, peripheral nerve fibers, on animal experimental pathological
      models and compared with the results of treatment of respective pathology in
      patients.

PMID- 12506748
TI  - [Psychophysiological components of electrostimulation of the visual analyzer and
      their use to choose adequate parameters of therapeutic current].
AB  - The paper deals with search for signs or controllers of the adequacy of chosen
      visual analyzer electrostimulation (ES) parameters accessible for an outpatient
      physician. The subjective characteristics of phosphene-elementary visual
      sensation under the influence of electric current on the visual tract are
      identified; changes in the properties of phosphene in response to those of ES
      parameters were traced. The subjective characteristics of phosphene indirectly
      evaluates the degree of visual tract lesion and may serve as a controller of
      adequacy of ES parameters. The resultant algorithm of management of the
      properties of each identified characteristics of phoshene significantly enhances
      the efficiency of therapeutical ES.

PMID- 12506749
TI  - [Film fluorography in current practice].
AB  - The stock of fluorographs is rather amplitidinous (N = 5000) in our country,
      which makes it full replacement expensive and longstanding. Therefore, it is
      expedient to update equipment gradually by taking into account a stepwise
      reduction in patients' irradiation. Five types of modernization of film
      fluorographs, including replacement of screens, fluorographic cameras, X-ray
      feeders, film sensitivity were investigated.

PMID- 12506750
TI  - [Systems analysis and modeling of organizational management processes of the
      regional public health system].
AB  - Scanty budgetary resources generate a need for optimally distributing the funds
      among different lines of expenditure in order to achieve the greatest possible
      social impact by taking into account the interests of different parties. A
      cognitive map and mathematical optimization models are proposed to control
      budgetary funds for financing the public health system.

PMID- 12506751
TI  - [Impact of the time of outpatient monitoring of patients with implanted
      pacemakers to evaluate dangerous changes in the parameters of apparatuses].
AB  - Patients with implanted pacemakers (PM) should pass outpatient monitoring at
      definite intervals given in the PM certificate. The paper shows that the
      monitoring periods in the patients are frequently violated, therefore the voltage
      of the PM battery is less than the critical level at which the PM is to be
      replaced. As the discharge of the battery is less than the critical level, the
      electronic unit of the PM begins first to regenerate an irregular sequence of
      stimulating pulses and then the generation of pulses stops. Thus, if the
      outpatient monitoring intervals in patients with implanted PM are over those
      given in the PM certificate, this will cause errors in encoding the causes of
      replacement of a PM, followed by dangerous changes in its parameters.

PMID- 12506752
TI  - [Introduction].

PMID- 12506753
TI  - [Significance of minimal residual disease for the estimation of the prognosis and
      for therapeutic decisions in solid tumors].
AB  - The detection of disseminated tumor cells in bone marrow and blood is
      increasingly used for staging and therapeutic decisions in breast cancer and
      other solid tumors. Molecular biological methods improve the diagnostic accuracy.
      Limitations of the approach relate to the lack of disease-specific marker genes.
      The detection of tumor cells in the bone marrow after primary therapy is a
      negative prognostic parameter in many solid tumours. Axillary lymph node
      dissection and histopathology remain the standard staging procedure in breast
      cancer, but nodal negative patients exhibiting tumor cells in the bone marrow
      have an inferior outcome and may benefit from adjuvant therapy. The
      immunohistochemical and molecular detection of tumour cells in lymph nodes
      reduces the number of truly nodal-negative patients considerably. Tumour cells in
      bone marrow and blood may be used to directly monitor therapeutic responses.

PMID- 12506754
TI  - [Direct molecular analysis of single disseminated cancer cells: a prerequisite
      for the development of adjuvant therapies?].
AB  - Cancer mortality has only marginally decreased in the last decades despite huge
      diagnostic and therapeutic efforts. Early dissemination of cancer cells has to be
      blamed for this finding, because ectopically residing cells are necessarily left
      behind by the surgeon. Consequently, this cell population has been designated as
      minimal residual disease that may eventually lead to systemic relapse months or
      years after presumed curative surgery. Paradoxically, systemic adjuvant
      treatments are currently administered without any precise knowledge about the
      target population of such drugs. Here it is argued that the direct analysis of
      disseminated cells may be a prerequiste for the development of future therapies
      since first molecular genetic data of single disseminated cancer cells suggest an
      excessive intercellular heterogeneity and distant relationship to the primary
      tumor.

PMID- 12506755
TI  - [Technical aspects of immunocytochemical detection of disseminated tumor cells in
      bone marrow].
AB  - Early and clinically occult hematogenous dissemination of tumour cells is
      considered a sign of systemic tumour progression, since recent data suggest that
      these cells are seminal precursors of subsequent distant metastasis. Single
      isolated tumour cells can be detected by means of immunocytochemical and
      molecular techniques at frequencies as low as 10(-5) to 10(-6) exploring
      different body compartments, such as bone marrow, peripheral blood and lymph
      nodes. This review summarises the currently available data on techniques that can
      be used to detect metastatic breast cancer cells in bone marrow and values their
      opportunities and limitations.

PMID- 12506756
TI  - [Importance of occult metastatic cells in the treatment of patients with breast
      and gastrointestinal cancers].
AB  - Early and clinically non-apparent hematogenous dissemination of tumor cells is
      considered an important prognostic factor and marker of tumor progression. This
      phenomenon is reported for tumor entities differing as much as breast and
      gastrointestinal cancers. First prospective studies point to the unique
      opportunity of therapy monitoring utilizing follow-up bone marrow aspirations
      before and after adjuvant therapy. First results of these studies further
      indicate that currently used treatment strategies such as chemotherapy may not be
      efficient enough to eliminate all metastatic cells in all of the cases studied.
      Apart from improved tumor staging, such screening efforts may not only help to
      improve planning and monitoring of adjuvant therapy (which at present is only
      possible retrospectively) but also help to design individualized targeted
      biological treatment. This review summarizes the currently available data on the
      importance of disseminated tumor cells for the treatment of patients with breast
      or gastrointestinal cancer.

PMID- 12506757
TI  - [Tumor biology of primary breast cancer and minimal residual disease].
AB  - The immunocytochemical detection of isolated disseminated tumor cells (ITC) in
      the bone marrow of breast cancer patients, what is called minimal residual
      disease (MRD), has been demonstrated to be of prognostic value in all stages of
      the disease. In order to definitely prove the origin of these cells from the
      primary tumor it is necessary to identify common factors on both tumor tissue and
      ITC, furthermore a more detailed characterization could help to improve their
      prognostic impact by defining certain subgroups and possibly establish new
      therapeutic strategies. We examined the expression/amplification of HER2neu, CD
      44 adhesion molecule and CD 31 angiogenetic factor on more than 200 primary tumor
      tissues by immunohistochemistry or fluorescence in situ hybridisation, resp., and
      found no sign. correlation with the detection of ITC. After a median follow-up of
      32 months only ITC in the bone marrow were of prognostic significance. In a small
      number of patients we examined the expression of topoisomerase II alpha, a key
      enzyme of DNA replication, and its predictive value of eliminating ITC by
      anthracyclin based chemotherapy. No correlation with the presence of ITC before
      or after chemotherapy could be found, yet pat. with topoisomerase II alpha neg.
      tumors showed a trend to reduced disease free survival. Because of the very low
      number of ITC per bone marrow sample, the direct characterization of these
      factors on ITC stays difficult without the possibility of tumor cell enrichment
      or cell culture. Preliminary results on multi colour stained samples indicate
      that a selection of certain biological factors takes place during tumor cell
      dissemination.

PMID- 12506758
TI  - Prognostic value of tumour cell detection in peripheral blood of breast cancer
      patients.
AB  - To investigate the prognostic value of tumour cells in peripheral blood (pB) of
      breast cancer (BC) patients, pB samples from 143 patients with benign lesions of
      the breast and from 467 BC patients were tested via a nested RT-PCR assay for
      mammaglobin mRNA. No sample from patients with benign lesions of the breast was
      found to be mammaglobin positive in contrast to 5/310 (2%) BC patients with no
      evidence of disease (NED) and 46/157 (29%) patients with metastatic disease (MD).
      Two hundred and eighteen BC patients with NED were followed for at least 12
      months. All five mammaglobin-positive BC patients relapsed 1-13 months after
      first examination of positive pB samples in contrast to 27/213 (13%) patients
      without detectable tumour cells in pB. Fifty-nine BC patients with MD were tested
      for mammaglobin expression in pB at the time of first diagnosis of MD; 20 of them
      (34%) were mammaglobin positive. Patients were followed for a median of 19 months
      (2-51 months). During this time, 19/59 (32%) died due to tumour progression. In
      Kaplan-Meier survival analysis, BC patients with mammaglobin-negative pB samples
      at time of diagnosis of MD lived significantly longer than mammaglobin-positive
      patients (log-rank test: P = 0.0013). In addition, mammaglobin was an independent
      prognostic parameter and the difference reached significance in univariate as
      well as in multivariate analysis (P < 0.01). We conclude that the presence of
      tumour cells in pB of BC patients is of prognostic value.

PMID- 12506759
TI  - [Incidence and prognostic significance of disseminated tumor cells in patients
      with cervical cancer].
AB  - The clinical course of cervical carcinoma is widely determined by locoregional
      recurrence. There is increasing data, however, that haematogenic micrometastases
      occur early during the disease and might result in distant recurrence during
      follow-up. These occult disseminated tumor cells in blood, lymph nodes and bone
      marrow escape conventional tumor staging. Therefore, molecular and
      immunoytochemical techniques based on markers against human papilloma virus or
      cytokeratins (CK) have been applied. At present, there is only one study
      available on the prognostic relevance of disseminated tumor cells in bone marrow.
      No correlation between the bone marrow status and overall survival was observed.
      Still, there was a strong trend towards shorter distant disease free survival in
      patients with a positive bone marrow status. In view of the data on disseminated
      tumor cells in other tumor entities, these early results might offer new options
      for refined tumor staging and improved treatment options.

PMID- 12506760
TI  - [Minimal residual disease in gastrointestinal tumors: tumor detection in bone
      marrow, blood and lymph nodes].
AB  - The cure of a tumor patient with gastrointestinal cancer is dependent on the
      extension of the primary tumor (TNM-classification) and the option of curative
      resection (R0-resection) at the time of operation. The additional application of
      multimodal therapy approaches has lead to an improvement of prognosis in
      different advanced tumor stages. Nevertheless, despite curative tumor resection
      about 50% of patients with locally advanced gastrointestinal cancer develop
      recurrent tumor disease or distant metastases and die tumor-related. A possible
      explanation is the seed of disseminated tumor cells in blood, bone marrow or
      lymph nodes pre-, intra- or postoperatively, but also during diagnostic
      procedures. Several studies have shown in the last years that the presence of
      minimal residual disease (MRD) influences the course of disease and the patient's
      prognosis after curative tumor resection. Although several groups have reported
      the prognostic impact of disseminated tumor cells in the different compartments
      of bone marrow, lymph nodes and blood, the phenomenon of minimal residual disease
      is not acknowledged as an established prognostic factor and is not integrated
      into the classification of the UICC. Therefore, no therapeutic consequences were
      drawn at present from the detection of disseminated tumor cells in patients with
      gastrointestinal cancer. A possible explanation are missing multi-center-studies,
      which confirm the results of the several single-center-studies. Standardization
      of study designs and methodical procedures and the evidence of reproduction are
      mandatory in order to value and interpret the multitude of studies and the
      available data in this field. Only these results will allow to decide if the
      presence and detection of disseminated tumor cells can alter the tumor staging
      and individualize or possibly minimize further oncological therapy strategies.

PMID- 12506761
TI  - [Immunocytochemical and molecular detection of minimal residual disease in blood
      and bone marrow in colorectal cancer].
AB  - Immunocytochemical and molecular biological methods to analyze minimal residual
      disease (MRD) in colorectal cancer in blood and bone marrow were compared. The
      concept of a study in the Donauspital will be presented which will permit a
      comparative judgement of minimal residual disease in blood and bone marrow in
      patients with colorectal cancer.

PMID- 12506762
TI  - [Detection, quantification and characterization of disseminated tumor cells].
AB  - There are different reasons why the detection of disseminated tumor cells (DTCs)
      in the hematopoetic system is important. On the one hand the detection of
      disseminated tumor cells can provide vital information about a tumor's tendency
      to develop metastases. In some localized epithelial but also in embryonic tumors,
      for example a correlation between disseminated tumor cells and unfavorable
      outcome was observed (6, 14). These studies are based on the assumption that
      those tumor cells which appear in the hematopoetic system at a very early stage
      are responsible for the development of metastases. Another important aspect is
      the monitoring of the disease response to cytotoxic drugs by quantifying DTCs.
      During and after therapy there is no other possibility (except for an operation)
      to either directly analyze the effects the therapy has on the tumor cells or to
      determine their biological characteristics. The dissemination in the hematopoetic
      system, however, reveals the response to therapy and the biological features of
      the tumor cells. The prerequisites for such bone-marrow diagnosis, however, is
      the unequivocal identification of disseminated tumor cells. So in order to avoid
      false positive results (which are a risk in bone-marrow diagnostics), a system
      was developed to distinguish tumor cells from non-neoplastic cells and to
      facilitate insights into the biological make-up of tumor cells (2, 11).

PMID- 12506763
TI  - [Cell proliferation and cell death in disseminated tumor cells].
AB  - The occurrence of occult metastases of solid tumors at initial diagnosis or
      during follow-up is of crucial therapeutical importance. The sensitive detection
      of such cells in hematological samples depends on tissue specific cellular
      markers. The demonstration of minimally disseminated tumor cells at a given
      timepoint is, however, only a snapshot, which does not give any information about
      the potential and dynamics of the cells in question. Functional differences may
      fundamentally influence the impact of a positive finding. The analysis of cell
      proliferation and cell death (apoptosis) in disseminated tumor cells, for
      instance, defines, whether the dissemination process is progressive or
      regressive. With a newly developed automatic image analysis station the
      investigation of functional parameters in isolated cells from clinical samples
      became possible. The studies presented here demonstrate, that such techniques
      allow an improved identification of isolated tumor cells with clinical
      importance.

PMID- 12506764
TI  - [Treatment of residual disease in chronic myeloid leukemia with STI-571
      (Glivec)].
AB  - Cytoreductive therapy can ameliorate symptoms in chronic myeloid leukemia (CML)
      but only treatment beyond hematologic remission aiming to affect the leukemic
      clone can improve prognosis. Up to now bone marrow transplantation is the only
      established therapy with the potential to completely eliminate the BCR-ABL
      positive cell population. Interferon-alpha (IFN-alpha) as well as cytosine
      arabinoside (ARA-C), particularly in combination, have been shown to be effective
      in achieving cytogenetic remission in some patients. With Glivec (STI-571) there
      is now a drug available which can induce major cytogenetic response in more than
      half of the patients who have failed IFN-alpha treatment and thus possibly delay
      or prevent blast crisis. Recent reports, however, have shown that primitive,
      quiescent, Philadelphia-positive stem cells are insensitive to STI-571 in vitro.
      Such cells could be the basis of relapse after termination of Glivec-therapy.

PMID- 12506765
TI  - [Basic principles of 18F-fluorodeoxyglucose positron emission tomography].
AB  - Positron emission tomography uses photons to receive regional information about
      dynamic, physiologic, and biochemical processes in the living body. A positron
      decay is measured indirectly by the simultaneous registration of both gamma rays
      created by the annihilation. The event is counted, if two directly opposite
      located detectors register gamma rays in coincidence. Unfortunately the detectors
      of a positron emission tomography system do not register only true coincident
      events. There are also scattered and random coincidences. Different types of
      positron tomographs are presented and scintillation crystals, which are in use
      for positron emission tomography are discussed. The 2D- and 3D-acquisition
      methods are described as well as preprocessing methods, such as correction for
      attenuation, scatter and dead time. For quantification the relative parameter
      standard uptake value (SUV) is explained. Finally hybrid systems, such as
      combined positron emission tomography/computed tomography scanners and the use of
      computed tomography data for attenuation correction are introduced.

PMID- 12506766
TI  - [Clinical impact of 18F-fluorodeoxyglucose positron emission tomography in the
      diagnosis of brain diseases].
AB  - In this review it will be discussed in which neurological disorders positron
      emission tomography can yield important diagnostic information. Because positron
      emission tomography is an expensive method indications have to be clearly
      defined. One important question concerns the differentiation of tumor recurrence
      and scar due to radiation therapy or an operation. The grading of brain tumors is
      another application. In HIV patients fluorodeoxyglucose positron emission
      tomography can separate lymphoma and toxoplasmosis. In the evaluation of dementia
      positron emission tomography can help to clarify the differential diagnosis.
      Another important area is the presurgical evaluation of epilepsy patients and
      patients with cerebrovascular disease in whom a surgical revascularisation
      procedure is planned. In extrapyramidal disorders, positron emission tomography
      can often help to establish the final diagnosis.

PMID- 12506767
TI  - Clinical applications of FDG-PET in oncology.
AB  - Positron emission tomography together with F-18-deoxyglucose (FDG) has emerged as
      a valuable clinical tool in the field of oncology. FDG-PET diagnoses, stages and
      restages most cancers with a high diagnostic accuracy. The effects of
      chemotherapy on tumour metabolism can be monitored with this whole-body
      technique. Recent studies have established a high prognostic accuracy of PET for
      predicting the clinical outcome of cancer patients. The current review addresses
      the role of FDG-PET for diagnosing, staging and restaging of lung cancer,
      colorectal cancer, lymphoma, melanoma and breast cancer staging and provides a
      brief outlook for future applications of clinical PET imaging.

PMID- 12506768
TI  - [18F-fluorodeoxyglucose positron emission tomography in the diagnosis of lung
      cancer].
AB  - Positron emission tomography (PET) is a new diagnostic procedure which allows to
      image tissue metabolism in vivo. Utilizing increased substrate metabolism or
      transport as a marker of malignant disease, primary as well as metastatic or
      recurrent lung cancer can be detected. This allows for improved differential
      diagnosis of pulmonary nodules or staging of non small cell lung cancer as has
      been documented in several studies. New applications of PET may include non
      invasive evaluation of tissue proliferation or hypoxia to predict individual
      prognosis or treatment response.

PMID- 12506769
TI  - [18F-fluorodeoxyglucose positron emission tomography in colorectal cancer: value
      in primary staging and follow-up].
AB  - Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) is a
      encouraging imaging technique allowing a highly sensitive whole-body search for
      malignant foci detected by their increased glucose metabolism compared with
      benign tissues. Several studies are now available that indicate its added value
      for diagnosis and staging of colorectal cancer. In all, patient management seems
      to be changed in 20-30% of patients who undergo Fluorodeoxyglucose positron
      emission tomography in addition to standard staging procedures.
      Fluorodeoxyglucose positron emission tomography is also useful in monitoring
      radiation therapy and chemotherapy. Regarding preoperative staging of primary
      colorectal cancer the literature is very limited.

PMID- 12506770
TI  - Clarifying the boundaries between the inflammatory and dystrophic myopathies:
      insights from molecular diagnostics and microarrays.
AB  - Clinical and histopathologic overlaps between the muscular dystrophies and
      inflammatory myopathies are being increasingly recognized. Most patients with a
      muscular dystrophy show improvement with prednisone treatment, although they will
      not be cured; many patients with idiopathic inflammatory myopathies are cured.
      Dysferlin-deficiency was recently recognized as a cause of late-onset dystrophy
      with substantial inflammation in muscle. Corticosteroid usage by these patients
      may result in nonrecoverable loss of strength. Therefore, it is important to rule
      out dysferlin-deficiency before initiating a course of corticosteroids. Newly
      emerging, genome-wide transcriptional profiling technology allows the
      identification of the interacting pathways that are active in the muscle of
      patients with inflammatory myopathies or dystrophies. There are several, complex
      molecular pathways; however, the comparison of expression profiles in patients
      with different muscle disorders permits the delineation of disease-specific
      patterns. It is hoped that novel approaches for treating the inflammatory
      myopathies and dystrophies can be derived from intimate knowledge of the pathways
      involved in each disease, and the key molecules that provide cross-talk between
      pathways.

PMID- 12506771
TI  - Differentiating idiopathic inflammatory myopathies from metabolic myopathies.
AB  - The metabolic myopathies are a heterogeneous group of diseases, including
      glycogenoses, disorders of lipid metabolism, and mitochondrial myopathies, that
      result primarily from inborn errors of metabolism. Most of these metabolic
      defects cause medical conditions that manifest early in life. Nevertheless,
      clinical presentations during the teenage years and adulthood are increasingly
      being recognized. Many of the clinical manifestations of these diseases are
      difficult to differentiate from those observed in the idiopathic inflammatory
      myopathies, especially polymyositis. A directed evaluation using the clinical,
      laboratory, and genetic approaches summarized in this article, however, should
      allow for the differentiation of most metabolic myopathies from polymyositis and
      other forms of idiopathic inflammatory myopathy. The diagnosis of a metabolic
      myopathy should be considered in patients who appear to have polymyositis but
      lack the characteristic changes of inflammation found on EMG, MRI, or muscle
      histology, or in such patients who are refractory to immunosuppressive therapy.
      The forearm ischemic exercise test is especially useful to screen for some inborn
      errors of glycogen metabolism or glycolysis and for myoadenylate deaminase
      deficiency. Thorough analysis of muscle tissue, including histology,
      histochemistry, biochemistry, and occasionally electron microscopy, is often
      necessary to make the diagnosis of a metabolic myopathy. Advances in molecular
      biology methods and knowledge of the precise genetic defects associated with
      these metabolic defects are dramatically increasing our capacity to diagnose
      patients with a widening range of myopathies. It is expected that, with further
      understanding of the mechanisms of the metabolic and idiopathic inflammatory
      myopathies, the differentiation of these disorders into their pathogenetic
      components, and the capacity to diagnose them will continue to improve. These are
      essential factors in improving genetic counseling and eventually the therapy of
      these serious, and currently incurable, disorders.

PMID- 12506772
TI  - Muscle biopsy findings in inflammatory myopathies.
AB  - The inflammatory myopathies encompass a heterogeneous group of acquired muscle
      diseases characterized clinically, by muscle weakness, and histologically, by
      inflammatory infiltrates within the skeletal muscles. The group of these
      myopathies comprise three major and discrete subsets: polymyositis (PM),
      dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains its
      characteristic clinical, immunopathologic, and morphologic features regardless of
      whether it occurs separately or in connection with other systemic diseases.
      Although the diagnosis of these disorders is based on the combination of clinical
      examination, electromyographic data, serum muscle enzyme levels, various
      autoantibodies, and the muscle biopsy findings, the muscle biopsy offers the most
      definitive diagnostic information in the majority of the cases. This article
      summarizes the main histologic features that characterize PM, DM, or IBM and
      emphasizes the main pitfalls associated with interpretation of the biopsies.

PMID- 12506773
TI  - Possible pathogenic mechanisms in inflammatory myopathies.
AB  - The limitations associated with the different approaches into the pathogenesis of
      the IIM have resulted in incomplete knowledge of disease mechanisms in myositis.
      In most research, in which muscle tissue was used to study the different aspects
      of disease, biopsies with inflammatory infiltrates have been selected. Although
      inflammatory cell infiltrates are a characteristic feature of myositis, selecting
      patients with inflammatory cell infiltrates for investigations naturally
      introduces a selection bias. Only a few studies have been published on patients
      without inflammatory infiltrates but with muscle weakness, and few studies have
      included follow-up biopsies after different therapies. The heterogeneity of the
      population of patients with myositis is another limitation of the studies of
      pathogenic mechanisms. Although most studies classify patients according to the
      Bohan and Peter criteria [118, 119], some studies used histopathologic criteria
      [6], and only a few studies included characterization with myositis-specific
      autoantibodies. Because myositis-specific autoantibodies are often associated
      with certain clinical profiles, classification according to autoantibody profiles
      could be important to define differences in the pathogenesis of different
      phenotypes [3]. From available data on pathogenic mechanisms it is evident that
      cellular and humoral immune responses are involved in disease mechanisms of
      myositis, but whether there is a muscle-specific immune response cannot be
      answered by current studies. It is likely that other mechanisms are important for
      development of muscle weakness, including metabolic disturbances, and muscle
      weakness could be caused by different mechanisms in different IIM subsets or in
      patients in different phases of the disease. There could be early changes, which
      reversibly affect the metabolism, and later, irreversible changes, that could be
      dependent on muscle fiber damage and replacement of muscle tissue by connective
      tissue and fat. Current findings suggest that cytokines, which are produced in
      muscle tissue from different cell sources including inflammatory cells,
      endothelial cells, and muscle fibers, could affect muscle function. Careful
      follow-up studies, including the effect of therapies targeting different
      molecules on molecular expression in muscle tissue, are likely to increase our
      knowledge on disease mechanisms. A better understanding of which molecules and
      mechanisms affect muscle function is likely to lead to improved, less toxic
      therapies in patients with myositis. Many possible target molecules for blocking
      therapies, especially the proinflammatory cytokines IL-1 and TNF-alpha, have been
      identified and should be studied in appropriate clinical settings given the
      currently poor outcomes of many patients with IIM.

PMID- 12506774
TI  - Clinical presentation of the idiopathic inflammatory myopathies.
AB  - The hallmark of the inflammatory myopathies is muscle weakness. Although this
      feature can lead to significant disability and impairment of activities of daily
      living, its initial presentation may not be recognized early. Older individuals,
      in particular, may feel that the changes caused by myositis reflect the effects
      of aging rather than those of a disease process, and diagnosis, therefore, may be
      delayed. This factor has negative impact on the response to therapy. Inclusion
      body myositis, with its insidious onset in older people, and laboratory findings
      which may not be markedly abnormal, presents a diagnostic challenge. DM, with its
      characteristic symptomatic rash, is generally brought to medical attention more
      quickly. Another area of diagnostic concern occurs when associated organ
      involvement precedes myopathy. This has been observed, for example, with
      interstitial lung disease, and again represents a challenge to physicians. In
      this connection, the antisynthetase syndrome presenting with fevers, Raynaud's
      features, arthritis, or pulmonary involvement may not initially be recognized as
      a manifestation of inflammatory muscle disease. Each subgroup of IIM may present
      with a variety of extramuscular features that can complicate diagnosis and alter
      therapy and prognosis. This is particularly true for the pulmonary, GI, and
      cardiac manifestations and when cancer is associated with myositis. For these
      reasons, such features of IIM should be carefully evaluated, treated, and
      monitored over the course of the illness; in some cases these may play a greater
      role in determining the outcome of patients with IIM than the muscle involvement
      itself. It is hoped that in the future increased familiarity with the
      manifestations of the inflammatory myopathies, together with a better
      understanding of the underlying pathogenesis, will lead to more rapid diagnosis
      and more effective treatments.

PMID- 12506775
TI  - Clinical features and outcomes of juvenile dermatomyositis and other childhood
      onset myositis syndromes.
AB  - The childhood myositis syndromes, primarily JDM, are relatively homogeneous
      diseases that have a good outcome in most cases, but are chronic, with poor
      outcomes, in a substantial number of cases. Because of the rarity of childhood
      myositis, and because there has not yet been a unified evidence-based approach to
      therapy, optimal treatment remains unknown. In clinic-based series the disease
      seems to be homogeneous but there are patients with rare clinical features,
      (e.g., cardiac, pulmonary, and neurologic disease), that impact prognosis.
      Racial, genetic, and other factors may lead to geographic variations in clinical
      presentations and outcomes, and perhaps further exploration of these influences
      will lead to a better understanding of the clinical features and outcomes seen in
      children. Our treatments are based on accumulated experience, but proper clinical
      trials have not been done. Ongoing registry studies, development of validated
      activity and damage assessment tools, large clinical trials, and continued
      investigation into the pathogenesis of the childhood myositis syndromes should
      lead to improved understanding and better treatments.

PMID- 12506776
TI  - Laboratory testing in the diagnosis and management of idiopathic inflammatory
      myopathies.
AB  - Laboratory testing commonly used to assess the idiopathic inflammatory myopathies
      (IIMs) can be divided into three categories: (1) measurement of serum activities
      or concentrations of muscle-derived factors--such as enzymes, myoglobin, and
      other molecules--in order to assess muscle injury; (2) immunologic tests that
      detect markers of the disease process, including serum autoantibodies that have
      been associated with myositis; and (3) general laboratory tests that are used to
      assess the patient's general status and medical condition. The laboratory
      assessment of muscle-derived factors that reflect muscle injury, and the
      determination of serum autoantibodies, play valuable roles in the diagnosis and
      management of the IIM. Enzyme elevations do not correlate with disease activity
      in all patients, however, and they must be interpreted within the clinical
      context. Autoantibodies can identify disease subsets with distinctive patterns of
      clinical manifestations, genetics, responses to therapy and prognosis, but
      disease-specific autoantibodies are present in only half of patients with IIM.
      Recent studies have defined additional myositis autoantibodies that may improve
      our capacity to diagnose and manage the IIM.

PMID- 12506777
TI  - Genetic and environmental risk factors for idiopathic inflammatory myopathies.
AB  - Although the studies discussed are beginning to reveal a number of genetic and
      possible environmental risk factors for myositis, further investigations are
      needed to fully understand and classify these syndromes. The difficulties in this
      process include small numbers of subjects with varying disease phenotypes
      available for study, polygenic risk factors for which it remains unclear which
      are primary and which are secondary or linked genes, and the lack of validated
      environmental exposure assessment tools. New technologies and international
      collaborative approaches, however, may overcome some of these difficulties and
      allow us to identify genetic and environmental risk factors, as well as the
      critical gene-environment interactions in the IIM and its subgroups. Nonetheless,
      our understanding of these diseases is still in the early stages. Although we
      have learned a great deal about these disorders through detailed investigations
      over the last several decades, we have even further to go to understand the
      environmental triggers and genetic susceptibilities for the myositis syndromes.

PMID- 12506778
TI  - Animal models of myositis.
AB  - Current animal models of human myositis include spontaneous, induced, and
      transgenic models. Although it is clear that none of these models possesses all
      the features of the human diseases, they may provide insight into the
      pathophysiologic mechanisms, and possibly the therapy, of inflammatory muscle
      disease. Because the human IIMs are phenotypically heterogeneous, but may be
      divided into more homogeneous subgroups based upon clinical or serologic
      features, it is possible that different pathogeneses are involved in different
      subgroups. It is unlikely that any single model would reproduce all features of
      the human disease. It may be possible, however, to gain insight into some
      subgroups of the human disease if certain animal models faithfully reproduce one
      or more subtypes or aspects of the IIMs. Because immunogenetic risk factors, and
      exposure to certain environmental agents important in triggering myositis in
      genetically susceptible persons, may be necessary components for human disease
      induction, transgenic approaches to humanizing murine immune systems and a better
      understanding of environmental risk factors will be productive avenues for future
      research. Additional investigations into the molecular basis of the human
      myositis syndromes and the pathogenesis of the spontaneous, induced, and
      transgenic animal models should ultimately allow for better understanding and
      therapy of these diseases.

PMID- 12506779
TI  - Outcome assessment in the adult and juvenile idiopathic inflammatory myopathies.
AB  - Through the recent efforts of multi-center collaborative study groups, a number
      of measures have been developed and partially validated to assess disease
      activity, disease damage, and health-related quality of life in adult and
      juvenile patients with IIM. Preliminary core set domains and core set measures of
      activity and damage have also been developed for adult and juvenile patients with
      myositis. Validated definitions of improvement and disability should be
      forthcoming in the next few years. These extraordinary developments will enable
      much-needed standardization in the assessment of the IIM, particularly in
      therapeutic and other clinical research studies. Despite this substantial
      progress, there is a need to develop more sensitive measures to assess IIM
      disease activity and damage, to further validate the existing tools, to define
      their performance characteristics in various IIM subgroups, to develop improved
      imaging techniques that are also quantitative, and to validate activation markers
      as surrogate measures. The ongoing cooperation of multiple specialists with
      expertise in these disorders, combined with emerging novel technologies, should
      continue to enhance the assessment of myositis. Improved clinical care and more
      rapid development of new therapies for patients with myositis will be the
      ultimate gains realized from these efforts.

PMID- 12506780
TI  - Idiopathic inflammatory myopathy: management and prognosis.
AB  - We are entering an exciting era in our understanding and management of the
      connective tissue diseases and, in particular, inflammatory myopathy. There is an
      established array of immunosuppressive regimens available to clinicians;
      rehabilitative and physical therapeutic interventions are evolving to provide
      many nonpharmacologic options to complement current therapy. Our ability to
      quantify [table: see text] the disease burden, using newly developed tools to
      distinguish myositis disease activity from disease damage, will allow us to
      measure with greater sensitivity the effects of treatment interventions. These
      measures, together with the development of international consensus regarding the
      standardization of many clinical trial design parameters, will enhance our
      capacity to conduct well-designed, prospective, multicenter studies of
      established and newly developed therapies. The explosion of immunopathogenetic
      information, in conjunction with novel biologic agents (Table 4), will afford
      investigators a treatment menu with multiple therapeutic options. The continuing
      challenge for the practitioner is the development of a logical, well-studied,
      multifaceted, and multidisciplinary holistic approach that optimizes the risk:
      benefit ratio for each individual patient and uses a rational combination of
      immunomodulatory agents in conjunction with ancillary measures.

PMID- 12506781
TI  - What's new on the dental scene?

PMID- 12506782
TI  - Experiments to determine the material properties of the periodontal ligament.
AB  - PHYSIOLOGY OF THE PERIODONTAL LIGAMENT: The periodontal ligament is a soft
      biological tissue that controls tooth movement under physiological loads by
      joining tooth and alveolar bone. Its various components differ in their material
      properties. Their spatial configuration and interaction are responsible for the
      reaction of the tissue in a loading situation. Due to the combination of fluid
      and elastic elements the periodontal ligament shows a viscoelastic behavior
      typical of soft biological tissues. It is characterized by non-linearity and time
      dependency, and additionally depends on loading history. BEHAVIOR UNDER EXTERNAL
      LOADS: In orthodontics, external loads are applied to the tooth crowns using
      orthodontic appliances. Since stresses and strains in the periodontal tissue,
      caused by the initial tooth movement, stimulate alveolar bone remodeling and thus
      orthodontic tooth movement, knowledge of the material properties of the
      periodontal ligament is fundamental to selection of an optimal force system for
      targeted tooth movement. OWN EXPERIMENTS: For this reason, typical properties of
      the viscoelastic material behavior of the periodontal ligament were tested
      experimentally in the present study, using samples from pig mandibles. This
      enabled the properties of force relaxation and hysteresis of this tissue, both of
      which depend on loading history, to be verified. CONCLUSION: The experimental
      results allow characterization of the tissue and thus contribute to an
      understanding of the biomechanics of tooth displacement under externally applied
      loads.

PMID- 12506783
TI  - Rectangular loops in inconsistent force systems: a laboratory investigation.
AB  - MATERIAL AND METHOD: [corrected] The force system delivered by the rectangular
      loop (R-loop) was the subject of this in-vitro investigation. The correction of a
      first-order irregularity was simulated in an inconsistent force system. Three
      types of R-loop made of 0.017" x 0.025" TMA wire but differing in length and
      insertion system were tested in a 3D strain gauge (Hottinger, Darmstadt,
      Germany). The buccal segment consisted of one molar and two bicuspids, with the
      first bicuspid as an active unit scheduled to be moved buccally into the dental
      arch. RESULTS: The first R-loop tested revealed too high a force magnitude to be
      recommended for clinical use. A loop connecting only two teeth and bypassing the
      second premolar delivered a favorable initial force of 85 cN with a drop of 20 cN
      per 1 mm deactivation. In order to achieve a translatory tooth movement, a buccal
      root torque must be bent in addition into the short horizontal leg of the R-loop.
      The use of a transpalatal arch is indispensable if adverse side effects are to be
      avoided.

PMID- 12506784
TI  - Torque capacity of metal and plastic brackets with reference to materials,
      application, technology and biomechanics.
AB  - AIM: The aim of the present study was to investigate slot deformation and the
      equivalent torque capacity of plastic brackets in comparison with those of a
      metal bracket in vitro and to simulate them under clinical conditions. MATERIAL
      AND METHOD: For this purpose the expansion characteristics of the brackets and
      their resistance to extraoral mechanical loading were compared in in-vitro
      activating experiments. In a further investigation, the labial crown torque of an
      upper central incisor was measured in a simulated intraoral clinical situation,
      using the Orthodontic Measuring and Simulation System (OMSS). Four types of
      bracket manufactured by Forstadent, Pforzheim, Germany, were tested: the plastic
      brackets Aesthetik-Line and Brillant, the latter from a previous series (Brillant
      old) and from a modified series (Brillant-new), and the metal bracket MINI-MONO.
      For testing purposes the brackets were torqued with 0.016" x 0.022" (0.41 x 0.56
      mm) and 0.018" x 0.022" (0.46 x 0.56 mm) ideal steel archwires (Remanium,
      Dentaurum, Ispringen, Germany). RESULTS: In the activating experiments,
      significantly higher torque losses and lower torquing moments were registered
      with both rectangular archwires with the plastic brackets than with the metal
      bracket. In the simulation tests, significantly higher torquing moments were
      registered with the metal bracket than with the plastic brackets. The OMSS model
      approximates the clinical situation, with the torque loss being notably higher
      than in the in-vitro activating experiments. This is due to the adjacent teeth
      giving the archwire additional play. In addition, the torquing process of the
      rectangular wire may deform the archwire, resulting in subsidiary forces.
      CONCLUSION: On the basis of the present results, the Brillant and Aesthetik-Line
      plastic brackets and the MINI-MONO metal bracket can be recommended for torquing.
      In view of the high torque losses, however, the torques programmed in the
      straight wire technique must be seen as questionable. It would be helpful to the
      practitioner if data were provided by the manufacturer on the flexing to be
      expected in plastic brackets, which has to be offset by additional torque or the
      possible renunciation of bracket torque.

PMID- 12506785
TI  - Esthetic aspects of orthodontic-surgical treatment of sagittal-vertical
      anomalies: the example of the short face syndrome.
AB  - BACKGROUND: Psycho-esthetic aspects play an important role in motivating patients
      to undergo combined orthodontic-surgical treatment as well as in the subjective
      appraisal of treatment outcome. The facial soft tissues are the crucial interlink
      between the underlying skeletal and dental structures and their perception by the
      patient and his social environment. TREATMENT OF SHORT FACE SYNDROME: In the
      therapy of Class II malocclusions with skeletal deep bite and short lower face
      (short face syndrome), the soft tissues and the psycho-esthetic treatment
      expectations of the patient are taken systematically and appropriately into
      account during treatment planning and evaluation. PATIENTS AND METHOD: The
      respective elements of the treatment concept are outlined and explained in this
      article. Based on the empirical evaluation of 15 patients treated according to
      this concept, the soft tissue changes in patients with short face syndrome and
      the changes in esthetic and psychosocial self-perception are reported. RESULTS:
      The results demonstrate the efficiency of the treatment concept in improving
      facial soft tissues, especially in the vertical dimension, and the resulting
      psycho-esthetic benefit to the patient.

PMID- 12506786
TI  - Cephalometric analysis in patients with obstructive sleep apnea. Part I:
      diagnostic value.
AB  - BACKGROUND: Morphological soft-tissue and skeletal anomalies of the upper
      extrathoracic airways are considered to be an etiological cofactor of nocturnal
      obstructive respiratory disorders. PATIENTS AND METHOD: In this study 106
      patients with a mean age of 56.1 +/- 8.4 years and a polysomnographic diagnosis
      of obstructive sleep apnea (OSA) were evaluated roentgenocephalometrically for
      soft-tissue and skeletal anomalies. Using cluster analysis and multivariate
      regression analysis, 18 skeletal variables, six pharyngeal variables and five
      hyoid variables were evaluated as predictor variables under the criterion
      variable "severity of the disorder". The body mass index (BMI), as a recognized
      risk factor of OSA, was taken separately into account. RESULTS: No direct
      correlation was found between the skeletal cephalometric findings and severity of
      OSA. Only the position of the hyoid as an expression of a probably adaptive
      alteration to a changed head posture and tongue position was found to be a
      significant parameter correlating with the severity of OSA. CONCLUSION: Whether
      cephalometric radiography is of direct diagnostic relevance in the diagnosis of
      OSA seems questionable in the light of the results of the present study.

PMID- 12506787
TI  - Bipendulum and quad pendulum for non-compliance molar distalization in adult
      patients.
AB  - BACKGROUND: Pendulum appliances are often used for compliance-independent molar
      distalization in the upper arch. However, the treatment of adult patients entails
      specific modifications to the pendulum appliance. Since both first and second
      molars have to be distalized in adult patients with a sagittal maxillary arch
      length discrepancy, it is appropriate to distalize the molars consecutively. TWO
      CASE REPORTS: The two case reports presented below show the clinical procedure
      using the bipendulum as well as the quad pendulum for unilateral and bilateral
      distalization of the second followed by the first molars. The treatment is
      compliance-independent.

PMID- 12506788
TI  - Using the Internet for teaching orthodontic x-ray analysis.

PMID- 12506789
TI  - Back to basics.

PMID- 12506790
TI  - Hospitals as community builders.

PMID- 12506791
TI  - Improving community health initiatives.

PMID- 12506792
TI  - Managing pediatric asthma.

PMID- 12506793
TI  - The role of nursing in information technology.

PMID- 12506794
TI  - Reining in the sales reps. PinnacleHealth protects patients and their privacy
      with a supplier relations program.

PMID- 12506795
TI  - Facility profile. D.C. hospital combines history and high-tech. George Washington
      University Hospital.

PMID- 12506796
TI  - Going into business.
AB  - Looking for a way to fight downsizing and add intrinsic value to your clinical
      engineering shop? Some in-house clinical engineering departments have converted
      costly operations into cost-effective enterprises by selling their technology and
      business skills to non-affiliated health care facilities.

PMID- 12506797
TI  - Custom interiors. Implementing healing design concepts in a small, rural
      hospital.
AB  - Many words have been written and symposia presented on the concept of healing
      design, but less has been written on the logistics of implementation, especially
      at small, rural hospitals. Recently, I was put in charge of an effort to
      introduce the concept at one of my hospitals in Washington state, and I am
      pleased to share lessons from my "school of hard knocks."

PMID- 12506798
TI  - Safeguarding the system. Devising a security plan for a health care network.
AB  - Health care systems have continued to evolve over the past several years. Some
      have been successful, some have reverted back to stand-alone or affiliated
      hospitals, and others continue to struggle with the system concept. Security
      departments must identify their new roles as this evolution plays out.

PMID- 12506799
TI  - Sprinkler basics. Some fundamental requirements for health care fire sprinkler
      systems.

PMID- 12506800
TI  - Raising the bar. High-performance cleaning enhances housekeeping quality and
      productivity.
AB  - Under pressure to contain or cut costs, health facilities often see the
      environmental services budget as an opportunity to save money. When the ES budget
      gets reduced, you are left with less money for supplies, equipment and labor.
      This wouldn't be so bad if you could reduce the space you clean or cut back on
      service levels, but that is seldom the case.

PMID- 12506801
TI  - "Insurance only" billing gets limited approval from feds.

PMID- 12506802
TI  - The real magic mountain?

PMID- 12506803
TI  - Showstoppers 2002. The score from the floor: part 1.

PMID- 12506804
TI  - The three R's: reciprocity, recertification and registry.
AB  - So what have we learned from all this? We have learned that "the three R's" need
      to be re-defined and reworked to make EMS a smoother-running profession. How do
      we, or how should we, go about making this change? In 1996, the National Highway
      Traffic Safety Administration (NHTSA) developed and published what has become
      known as "The Agenda," in which the authors suggested numerous ways to overcome
      certain situations in EMS. One situation in particular, and very relevant to the
      discussion, is the need for a National Office of EMS, or a federal lead EMS
      agency which is mandated by law. With the advent of the lead agency, each state
      has a sole agency, mandated by law, that adheres to national policy, but is still
      responsible for developing and overseeing its own statewide system. If we were to
      interpret the 10th and 14th Amendments, putting an "EMS spin" on them, we could
      say that the United States Constitution has granted each state the power to
      create EMS legislation. Accordingly, EMS certification and/or licensure is
      governed by each individual state. Having said that, each state does have its own
      office, but how many of those offices work together to make EMS, and particularly
      the "Three R's," standardized across the country? Another option is to contact
      your EMS-related service director, local or regional EMS council, state EMS
      office, and even your local or state political officers, and discuss these issues
      and potential solutions with them. Public opinion is a very strong tool, which,
      if used wisely, can alter the direction of certain issues.

PMID- 12506805
TI  - Heavy metal. Weighing the mercury-free options.

PMID- 12506806
TI  - Standards in the name of NAHIT. National Alliance for Health Information
      Technology.

PMID- 12506807
TI  - A guiding hand. CDC releases hygiene recommendations.

PMID- 12506808
TI  - Patient rationings.

PMID- 12506809
TI  - Stats. A sterilization cycle. Growth patterns dependent on type.

PMID- 12506810
TI  - Family friendly.

PMID- 12506811
TI  - Grading scales used in the management of aneurysmal subarachnoid hemorrhage: a
      critical review.
AB  - The use of grading scales to predict clinical outcomes following aneurysmal
      subarachnoid hemorrhage (aSAH) is commonplace. In recent times management of aSAH
      patients has developed such that surgical intervention is taking place earlier in
      the course of the illness. Given the complex and multifactoral clinical picture
      of these patients, there is an increased impetus to examine and reevaluate the
      relative merits and predictive characteristics of grading scales. The measurement
      characteristics and predictive power of the following instruments were reviewed:
      Fisher Scale (FS), Glasgow Coma Scale (GCS), Glasgow Outcome Score (GOS), Hunt
      and Hess (HH) Scale, Karnovsky Performance Scale (KPS), and the World Federation
      of Neurological Surgeons (WFNS) Scale. No uniformly conclusive findings were
      found when the HH Scale, GCS, and WFNS Scale were used to predict clinical
      outcomes. No instrument consistently outperformed any other across age or
      severity. Contradictory findings were reported. Difficulties were encountered in
      comparing instruments because of administration, scoring schemes, timing of
      assessments, and psychometric properties, such as interrater reliability. Reports
      on newly developed instruments often lacked the replication data necessary to
      effectively compare measures currently in use. The timing of measurements and the
      use of serial measures emerged as important factors in the prediction of clinical
      outcomes. Assessments taken close to the time of surgical intervention were found
      to have superior predictive abilities.

PMID- 12506812
TI  - Periventricular leukomalacia: pathophysiological concerns due to immature
      development of the brain.
AB  - Periventricular leukomalacia (PVL) is a result of injury and necrosis of
      myelinated fibers around the lateral ventricles. PVL is now considered the
      principal form of brain injury in preterm infants. This injury can have long-term
      effects on physical, motor, sensory, cognitive, and social development. Some
      proposed pharmacological treatments being considered to aid in prevention of this
      injury are raising concerns because they have failed to show evidence of efficacy
      or have potential for deleterious long-term effects. Current treatment is aimed
      at injury prevention; therefore, nurses play a critical role. Awareness of the
      pathophysiologic concerns about preterm neonates can help nurses focus their
      assessments to identify patients at risk.

PMID- 12506813
TI  - Ritalin revisited: does it really help in neurological injury?
AB  - Methylphenidate (Ritalin) is a commonly used central nervous stimulant. It has
      been used in various neurological conditions, including attention deficit
      disorder, depression, and narcolepsy. Methylphenidate has been advocated in
      patients with traumatic brain injury and stroke for a variety of cognitive,
      attention, and behavioral problems. It also has been shown to speed recovery from
      poststroke depression so that patients can participate more fully in
      rehabilitation programs. Research suggests that it also may have a role in
      augmenting activity of injured neuronal tissue in the comatose patient, thus
      facilitating a return to consciousness. The neuroscience nurse plays an important
      role in monitoring response to Ritalin, including identifying its side effects. A
      review of the limited studies on the use of Ritalin, its mechanisms of action,
      dosing, and weaning provide a current understanding of this adjunctive agent's
      role in treatment for the neurological population.

PMID- 12506814
TI  - Parkinson-plus patients--an unknown group with severe symptoms.
AB  - The Parkinson-plus syndromes, which include multiple system atrophy (MSA),
      progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are
      still not well-known. Research concerning diagnosis and treatment is ongoing;
      nursing studies are lacking. Therefore, the aims of this study were to survey the
      patients about their symptoms, their previous contacts with physicians and other
      caregivers, the questions about their disease that were of most importance to
      them, and their perceived quality of life. The mapping caregivers and symptoms
      (MCAS) questionnaire, which was constructed for the study, and the Nottingham
      Health Profile (NHP), were used. Twenty-three patients participated. Early in the
      course of the disease Parkinson-plus patients needed to consult physicians from
      different specialties and many other professional caregivers because of a
      multitude of problems such as slow movements, weak voice, stiffness, dysphagia,
      muscle pain, and incontinence. The NHP revealed that many participants ran out of
      energy, and this affected their everyday lives and leisure time. As the disease
      progressed, palliative needs successively increased. Patients in all stages
      wanted to know about the disease course and their prognosis and about issues that
      could give them hope. In accordance with palliative care philosophy, caregivers
      can help direct the patients' hope from cure to a palliative goal, with a focus
      on quality of life.

PMID- 12506815
TI  - Comparison of a standard neurological tool with a stroke scale for detecting
      symptomatic cerebral vasospasm.
AB  - The purpose of this study was to critically analyze the effectiveness of two
      tools used by nurses to assess neurological status of individuals at risk of
      developing cerebral vasospasm following aneurysmal subarachnoid hemorrhage due to
      aneurysm rupture. Early detection of vasospasm provides an opportunity for prompt
      treatment so that further ischemia or infarction can be prevented. We
      hypothesized that the National Institutes of Health Stroke Scale would detect
      symptomatic vasospasm earlier than the standard neurological record currently
      used in the practice setting of a tertiary care teaching hospital. Thirty
      participants were entered into the study, and a differential diagnostic process
      identified 15 with symptomatic vasospasm. Quantitative prospective and
      retrospective analysis showed that there was no statistical difference between
      the two scales in early detection of vasospasm. This finding may partially be
      explained by the clinical similarities between the vasospasm and nonvasospasm
      groups and by the challenges experienced by nurses in administering the stroke
      scale. Clinically relevant observations suggested the stroke scale was more
      effective in the assessment of focal symptoms. Qualitative content analysis of
      nursing notes also provided insight into clinical findings not captured on either
      scale regarding generalized changes such as restlessness, impulsiveness, and
      unusual behavior. This study demonstrates the need to develop a more appropriate
      tool for early detection of vasospasm.

PMID- 12506816
TI  - Glial tumors--new approaches in chemotherapy.
AB  - While malignant glioma remains a devastating diagnosis, recent significant
      advances are occurring, which we hope will have a positive effect on patient
      survival. Agents designed to target specific processes and structures involved in
      tumor cell division and innovative combinations of cytotoxic and cytostatic
      therapies offer future hope for the efficacious treatment of gliomas.

PMID- 12506817
TI  - Clearance of cervical spines in adult trauma patients.
AB  - Clearing the cervical spine in adult trauma patients must be done cautiously and
      methodically. Practitioners must be able to recognize abnormalities not only in
      the patient's neurological examination but also on the radiographic views
      obtained. A missed cervical spine injury can be a significant and catastrophic
      error. Nurse practitioners in the emergency department, as well as those working
      on an inpatient trauma service, should be confident in their ability to manage
      the cervical spine in the adult trauma patient population.

PMID- 12506818
TI  - The development of the tool for optimizing written productivity (TOW-P).
AB  - Many school-aged children experience difficulties in written productivity, which
      result in a large number of referrals for school-based Occupational Therapists
      (OTs). Health care practitioners are being called upon to establish consistent
      practice, yet there are presently no guidelines to facilitate consistency in this
      clinical area. The Tool for Optimizing Written Productivity (TOW-P) was developed
      to assist OTs in decision-making regarding intervention selections for this
      population. A pilot study and a province-wide survey yielded specific frequencies
      of intervention for different written productivity issues that can be used to
      guide a therapist's selection of interventions.

PMID- 12506819
TI  - Test-retest reliability of the Motor-Free Visual Perception Test Revised (MVPT-R)
      in children with and without learning disabilities.
AB  - The Motor-Free Visual Perceptual Test Revised (MVPT-R) is an updated edition of
      the original test with the addition of four items and normative data for 9-11
      year-old children. Test-retest reliability studies on the MVPT-R are not
      reported. The purpose of this paper is to report the test-retest reliability of
      the MVPT-R in children with and without learning disabilities. The MVPT-R was
      administered to 38 children with identified learning disabilities and 37 control
      children (aged 7-10 years) on two separate occasions within a 2.5 week window of
      time. Inter-rater reliability agreement between examiners was 99%. Intra-class
      correlations for perceptual quotient scores ranged from .63-.79 and perceptual
      age scores ranged from .69-.86. Pearson product moment correlations for
      perceptual quotient scores ranged from .70-.80 and perceptual age scores ranged
      from .77-.87. Results suggest moderate test-retest reliability for the MVPT-R
      with more stability in visual perceptual scores for children with learning
      disabilities. This information will be helpful for therapists using the MVPT-R as
      a descriptive measure for children.

PMID- 12506820
TI  - The effect of therapeutic horseback riding on gross motor function and gait speed
      in children who are developmentally delayed.
AB  - The purpose of this study was to measure the effects of a seven-week therapeutic
      horseback riding program and to determine if changes were retained after
      therapeutic riding was discontinued. A repeated-measures within-participants
      design was used to assess performance on the Gross Motor Function Measure and
      timed 10-meter walk in seven developmentally delayed children. A statistically
      significant improvement in gross motor function was found in post-intervention
      measures. Improvements were maintained seven weeks after therapeutic riding had
      ended. No considerable difference in gait speed was noted. This study indicates
      that therapeutic riding may lead to improvement in gross motor function in
      developmentally delayed children and that these improvements remain once
      therapeutic riding ceases.

PMID- 12506821
TI  - The effect of food textures on intake by mouth and the recovery of oral motor
      function in the child with a severe brain injury.
AB  - The objective of this study was to evaluate the effect of different food textures
      on the amount of food intake by mouth and the recovery of oral motor function in
      children after acquired brain injury. The subjects were three children aged 3,
      12, and 14 years with severe brain injury. A single case study with a Latin
      square design was used to randomly allocate three different food textures
      (pureed, minced, and soft) for each of three daily meals for up to 11 days per
      child. The primary outcomes were the amount of food intake by mouth and oral
      motor function, as measured by the Behavioral Assessment of Oral Functions in
      Feeding. Results indicated that texture and the person feeding the child are
      important variables for intake. The most clinically important conclusion was that
      the variability in each child with acquired brain injury reinforces the need for
      an individualized approach to decisions and treatment for feeding.

PMID- 12506822
TI  - Motor skill and mobility recovery outcomes of children and youth with traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) is a major cause of disability in children. Along
      with other neurological clinical sequelae, children often exhibit motor skill
      impairment and limitations in functional mobility following TBI. The purpose of
      this annotated bibliography is to: (1) familiarize therapists with the literature
      available regarding motor skill and mobility recovery outcomes for children and
      adolescents with TBI; (2) assist therapists in the selection of motor skill and
      mobility outcome assessments for use in clinical practice; and (3) provide
      therapists with comparisons of outcomes for external benchmarking. A number of
      reports document motor and mobility recovery outcomes as well as recovery in
      other domains. Studies vary, however, in design, sample size, number and type of
      outcome assessments used, time since injury at assessment(s), and the
      consideration of correlating factors such as age at time of injury and injury
      severity. Further research is needed to describe clinical, satisfaction and
      resource utilization outcomes, determine outcome predictors, and provide evidence
      for therapeutic intervention effectiveness.

PMID- 12506823
TI  - Computerized platform posturography for children: test-retest reliability of the
      sensory test of the VSR System.
AB  - The purpose of this study was to examine the consistency of scores from typically
      developing children on the sensory test of the NeuroCom International VSR System.
      Participants included 18 children between five and nine years of age. Postural
      sway was measured using the VSR System, a computerized platform posturography
      assessment tool. The sensory test protocol examines the relative contributions of
      the visual, somatosensory, and vestibular systems to maintain postural stability
      by systematically manipulating the availability and accuracy of sensory inputs.
      Test-retest intraclass correlation coefficients for all four sensory conditions
      ranged from .76 to .83.

PMID- 12506825
TI  - Building and maintaining a stronger workforce: CLMA tackles the clinical
      laboratory staffing shortage.
AB  - During the mid- to late 1990s, CLMA heard frequent comments and requests for help
      from its membership related to the problem of staffing their laboratories. As
      this information was collected and addressed on an individual basis, CLMA's
      leadership quickly realized the potential impact such staffing shortages would
      have on both its membership and the clinical laboratory industry. As this issue
      has eclipsed our health-care horizon, CLMA has developed and participated in a
      variety of activities to address the staffing shortage, from coalitions and
      committees to surveys and seminars. This article highlights some ways in which
      our association has created strategies and sources to help its membership and the
      industry at large avoid the crisis.

PMID- 12506826
TI  - Medical laboratory workforce trends and projections: what is past is prologue.
AB  - During the last several decades, supply and demand trends for clinical laboratory
      personnel have been cyclical. Factors such as quantity of graduates from
      accredited training programs, quality and quantity of career recruitment, growth
      of new technologies, automation, downsizing, and consolidation of services have
      affected the balance of workers needed to meet demand. More recently, several
      additional forces led to a potential long-term shortage of clinical laboratory
      personnel. This article reviews major studies of staffing strategies and outlines
      strategies of the American Hospital Association to ease the current shortage
      crisis.

PMID- 12506827
TI  - The value of the laboratory professional in the continuum of care.
AB  - The community laboratory often is relegated to the subterranean levels of the
      hospital, and it feels, at times, that the laboratory profession has been put in
      the basement as well. It is incumbent upon those of us who work in the clinical
      laboratory to ensure that the daily contributions made by the laboratory to the
      lives of our patients are not overlooked by our colleagues or by the future
      generation of laboratorians. We can expand our parochial view of the laboratory
      and begin to understand and to achieve the institutional goals of cost-effective
      patient care. Using a data-driven approach, we can articulate the real benefits
      of delivering quality laboratory service near the patient and secure the
      institution's investment in that core competency. Fostering the growth of
      community laboratory insourcing compounds these benefits and provides an
      environment for the creation of job enrichment opportunities.

PMID- 12506828
TI  - Educating laboratory staff for the future.
AB  - The escalating shortage of laboratory workers is compounded by fewer graduates of
      accredited programs and changes in the work environment. Looking ahead, the
      National Accrediting Agency for Clinical Laboratory Sciences held a national
      conference and invited a wide spectrum of stakeholders to address what CLS/MT and
      CLT/MLT skills will be needed in the years 2005 and 2015. The results of the
      conference were used to revise accrediting standards. Faculties in accredited
      programs are working to transform the new standards into new curricular
      configurations. Laboratory administration must contribute to this transformation
      by actively supporting the clinical components of education and maintaining
      strong communication links with academic institutions. Administration needs to
      lead the way in creating a laboratory workplace that is more interesting and
      inviting to those making career decisions. It will take the combined efforts of
      laboratory administration and staff, educators, and professional organizations to
      restructure the workplace for the future and to redesign curriculum for
      appropriately educating professionals. This will be an important step toward
      addressing the staffing crisis in the laboratory.

PMID- 12506829
TI  - Using career ladders to motivate and retain employees: an implementation success
      story.
AB  - In October 2000, Phoenix-based Sonora Quest Laboratories, LLC (SQL), commissioned
      The Gelfond Group to survey SQL employees. Responding to negative survey scores,
      SQL developed and implemented an entry-level career ladder for line staff of the
      specimen management/referral testing department. The program was piloted in
      February 2001, and was implemented fully shortly thereafter. The ladder was
      designed to provide job enrichment opportunities through company-conducted
      training and advancement provisions. It contained requirements for productivity
      and quality of work performed in addition to increasingly rigorous training and
      competency documentation. Employees were accountable for their own advancement
      and for ensuring that all documentation was complete. Advancement was automatic
      once requirements were completed. Pay increases accompanied each advancement on a
      predetermined scale. At the end of 12 months, employee turnover dropped from 39%
      to less than 20% annually. Both productivity and morale improved, and results on
      a second employee survey indicated dramatic improvement in five key areas. The
      career ladder concept has been replicated successfully in several other
      departments, including phlebotomy, and a six-tiered ladder is under development
      for the clinical laboratory. It will encompass CLA, MLT, and MT positions from
      entry level to technical coordinator.

PMID- 12506830
TI  - Mentorship: a successful tool for recruitment, recognition, and advancement.
AB  - Mentoring is a valuable tool for recruitment, retention, and staff personal
      satisfaction in these chaotic times. Effective staffing of health-care
      laboratories has become increasingly difficult as decreased numbers of qualified
      medical technologists graduate from medical technology programs. Laboratory
      managers experience loss of valuable, seasoned employees as those workers pursue
      fields other than the laboratory. Mentorships to assist young people in making
      clinical laboratory science career choices can help to expand the number of
      medical technologists entering the job market. Mentorships to expand the
      abilities of experienced technologists and to afford opportunities for
      advancement can enhance job satisfaction and retention.

PMID- 12506831
TI  - Staff retention and empowerment: functions of leadership.
AB  - Regardless of any organization's structure and technology, the most potent
      leverage for exceptional performance and quality assurance resides within
      personnel. Retention of empowered, committed staff who believe in their
      organization's purpose and leadership is important to an organization's success.
      The Clinical Laboratory Sciences (CLS) profession faces a different kind of
      crisis, not only one of economics, but also one of quality because of lost
      professional expertise. This dilemma is because of profound neglect of the
      organization's greatest asset--its CLS professionals. Retention of expert CLS
      professionals requires a dramatic change in management's belief system regarding
      the value of their assets. Laboratory leaders must create a culture of empowered
      people with the freedom to exhibit self-direction toward achieving the
      organization's mission and goals. Managers must consider employees valuable
      enough to invest in their professional growth. A laboratory's long-term
      sustainability and economic performance will depend on a committed workforce.

PMID- 12506832
TI  - Responding to the medical laboratory staffing shortage: the Canadian perspective.
AB  - Shortages of qualified medical laboratory personnel have not been a problem in
      Canada since the early 1960s, when the profession experienced a growth that far
      exceeded training capacities. Massive immigration, primarily from the United
      Kingdom, provided a temporary patch for the urgent human resources (HR) supply.
      Medical laboratory technologist training program enrollments were increased
      rapidly, and, by the early 1970s, more than 1,200 new graduates were generated
      each year. In the late-1980s, a trend evolved in Canada that raised concern about
      the ability to attract suitable applicants to careers in medical laboratory
      technology. However, that issue quickly faded as a priority when the health
      reform of the 1990s struck Canada.

PMID- 12506833
TI  - Riding the wave: what health care can learn from other industries.
AB  - Many staffing challenges face 21st century health-care employers. If a rising
      tide lifts all ships, then tidal surges and currents also affect all ships.
      Recruitment and retention represent two major human resources issues facing
      employers. Economic downturns, the rising cost of postsecondary education,
      competition for the best graduates, reduced desire to accept relocations, forced
      overtime and shift work, and the graying of the workforce are some of the
      challenges faced by employers. Another challenge is the lack of loyalty in
      today's business world. Corporations and nonprofits both show reduced loyalty to
      employees, who, in turn, limit their willingness to remain loyal to one employer.
      Competition for a shrinking pool of workers results in employees being more
      selective about where to begin their careers and being less loyal once they
      arrive. These factors negatively affect productivity and make it increasingly
      imperative for employers to understand how best to recruit and to retain the most
      talented workers they can find. Health care and other industries should be
      prepared for the surging tides of change.

PMID- 12506834
TI  - Surviving the staffing crisis.
AB  - Numerous seminars and articles discuss the staffing shortage in health care and
      in the laboratory. Most of these have dealt with the importance of retaining and
      recruiting good employees. Given the median age of laboratories (49 years old),
      the decrease in medical technology schools, and a decline in people choosing the
      laboratory profession, the staffing shortage is here to stay and will affect the
      way we run our laboratories for years to come. Clinical systems managers need to
      identify and make the changes necessary in their laboratories to deal with the
      staffing shortage while maintaining quality testing and good customer service.
      This article will review the need and the process to assess laboratory operations
      along with the needs of the facility and/or health-care community. Obvious and
      not-so-obvious ideas for streamlining laboratory efficiencies along with
      maintaining high levels of quality and service will be presented.

PMID- 12506835
TI  - The laboratory manager's new role as retention officer.
AB  - Clinical laboratories are in the midst of a staffing crisis. Low salaries,
      stressful working conditions, and a lack of advancement opportunities make it
      difficult to attract new people. Now, more than ever, it is critical to keep your
      current staff happy. The key could be your management style. Salaries and
      benefits may tempt employees to look around, but poor management surely will make
      them leave.

PMID- 12506836
TI  - Keeping the human in human resources: finding and keeping star employees.
AB  - People are an organization's most valuable asset. An enterprise's success is
      determined by the people selected to work there. Most laboratorians are drawn to
      the profession because of their analytical and organizational preferences.
      Typically, they focus on the task, and especially on the process of completing
      analyses. Many are promoted to supervisory or management positions because of
      technical expertise. Technical managers often forget, however, that people
      perform the assays. Invest time and energy in identifying the right people for
      your laboratory, in cultivating the environment necessary to attract great
      people, and in developing a positive, proactive plan to keep stars on your team.
      When you keep your focus on the human element, the bottom line will take care of
      itself.

PMID- 12506837
TI  - Avoiding crisis: right-sizing staffing for the future.
AB  - Workforce issues, especially recruitment and retention of qualified laboratory
      staff, are major strategic issues that will continue to face laboratory managers
      over the next 10 years. Major factors affecting the laboratory labor market in
      the next decade include increased health-care and laboratory testing needs of an
      aging population, the graying of the laboratory workforce as baby boomers retire,
      and new technology development. At least two of these factors will increase the
      demand for qualified laboratory professionals. Vacancy rates for laboratory
      professionals are increasing at a significant rate and will continue over the
      next 10 years. Planning will require creativity in staff recruitment and
      retention strategies and in human resources. Laboratorians no longer will have
      the luxury of using medical technologists for nonspecialized testing assignments
      and will need to develop more creative recruiting approaches using fewer highly
      qualified testing personnel. This article proposes a staffing deployment model
      that will use medical technologist education and skills more appropriately, will
      improve retention of medical technologists, and will alleviate the shortage of
      medical technologists by reducing dependence on them as routine laboratory
      testing personnel.

PMID- 12506838
TI  - Motivating 21st century employees.

PMID- 12506839
TI  - Questioning proposed practices: individual responsibility in organizations.

PMID- 12506840
TI  - Common cent$ 9: The real cost of employee turnover.

PMID- 12506841
TI  - Creating an anatomic pathology laboratory--examining the time line.

PMID- 12506842
TI  - The laboratory survey: education at your fingertips.

PMID- 12506843
TI  - Improving your environment for recruitment and retention.

PMID- 12506844
TI  - Ancillary technicians--bridging the gap between laboratory and radiology.

PMID- 12506845
TI  - Securing staff salary adjustments and raises.
AB  - Salary issues have plagued laboratories for as long as there has been a labor
      shortage, and the situation grows more complicated. At the Virginia Commonwealth
      University Health System (VCUHS) in Richmond, Virginia, competition for
      laboratory staff now comes not only from area hospitals and health-care companies
      but also from non-health-care industries. Shorter shifts, less stress, and better
      hourly wages offered by fast food chains and retail stores lure away the young
      workers traditionally hired for entry-level laboratory positions. Clearly, a
      salary adjustment is necessary.

PMID- 12506846
TI  - Building staff morale.

PMID- 12506847
TI  - What's cooking with E. coli? The new, more sinister face of a familiar pathogen.

PMID- 12506848
TI  - Olympus VP Stephen Wasserman shares his views. Interview by C. Anne Pontius.

PMID- 12506849
TI  - Precautions, common sense help reduce the risks of 'eavesdropping'.

PMID- 12506850
TI  - Immunodiagnostic systems provide new, essential tests.

PMID- 12506851
TI  - Lab groups continue to push hard for Medicare inflation update; controversy brews
      over rapid HIV test.

PMID- 12506852
TI  - Superimposed cold stress-induced hypothalamic-pituitary-adrenal response during
      long-duration restraint stress.
AB  - It has been reported that animals exposed to prior stress exhibit enhanced,
      reduced or equivalent hypothalamic-pituitary-adrenal (HPA) response to a
      subsequent acute stressor. We demonstrated previously that a long-duration
      restraint stress (RTS) evoked adaptive change, characterized by transient
      increase and gradual recovery to basal level in c-fos mRNA/c-fos protein (Fos)
      expression in the hypothalamic paraventricular nucleus (PVN) and in plasma
      adrenocorticotropin (ACTH) levels, although circulating corticosterone (CORT)
      remained at a high level. In order to investigate the HPA response to another
      stressor during the adaptive phase of long-duration RTS, we superimposed acute
      cold stressor (CS) to 16 hours RTS rats. Superimposed CS-induced re-expression of
      c-fos mRNA/Fos in the parvocellular region of the PVN (PVNpv) was observed in 16
      hours RTS rats. The degree of expression of c-fos gene in superimposed CS rats
      was the same as those observed in single CS rats. The plasma ACTH levels induced
      by superimposed CS in 16 hours RTS rats were significantly higher compared with
      those in single CS rats. On the other hand, there were no significant differences
      between plasma CORT levels induced by superimposed CS in 16 hours RTS rats and
      those in single CS rats, and between plasma CORT levels before and after
      additional CS exposure in 16 hours RTS rats. The present study indicated that c
      fos gene expression in PVN induced by superimposed CS was normo-responsive, ACTH
      secretion was hyper-responsive (facilitation), CORT secretion was slightly
      increased, but not hyper-responsive in long-duration RTS rats. These findings
      suggest that stress response induced by superimposed CS during long-duration RTS
      may occur in a different way at each level of the HPA.

PMID- 12506853
TI  - Monomeric sarcoplasmic reticulum Ca(2+)-ATPase is functionally active.
AB  - cRNAs for wild type and a functionless mutant of sarcoplasmic reticulum (SR)
      Ca(2+)-ATPase were co-injected into Xenopus oocytes in various molar ratios. SR
      Ca(2+)-ATPase activity of the microsomal fraction prepared from the injected
      oocytes increased linearly with increasing amounts of wild type cRNA. This result
      suggests that monomers are functional units of membrane-bound SR Ca(2+)-ATPase.

PMID- 12506854
TI  - Reproduction of typical electrocardiographic findings of the Brugada syndrome
      using modified precordial leads.
AB  - We present a case of a patient with Brugada syndrome and aborted sudden cardiac
      death in whom the typical Brugada sign (coved-type ST segment elevation in the
      precordial leads V1 through V3) was always reproduced by the precordial leads
      recording on the second intercostal space even after the typical sign had
      disappeared. The finding indicates that recordings of precordial leads on the
      higher intercostal spaces are important to unmask the ST elevation in suspected
      patients with Brugada syndrome.

PMID- 12506855
TI  - Effects of lithium addition on daily activity and psychiatric symptoms in
      schizophrenic inpatients.
AB  - Lithium addition to neuroleptic treatment brought about some improvement in 6
      schizophrenic inpatients. In 3 of them, however, enhancement of daily activity
      did not parallel improvement in psychiatric symptoms. This suggests that lithium
      addition may enhance daily activity independently of psychiatric symptoms, and
      that lithium effects should also be assessed from the viewpoint of daily
      activity.

PMID- 12506856
TI  - Musculoskeletal disorders and skin disease among workers in a Japanese CD
      manufacturing plant.
AB  - We investigated the prevalence of musculoskeletal disorders (MSD) and skin
      disease within a Japanese compact disk (CD) manufacturing plant. For this study,
      a stratified cross-section of workers completed self-reported questionnaires
      distributed over a 6-month time period. Low back pain (LBP) was the most commonly
      reported category (affecting 20.1%), followed by MSD of the shoulder (15.4%),
      neck (10.1%) and head (5.4%). Dermatitis was the most frequent skin disease
      (affecting 8.1%), followed by eczema (3.4%), acne (3.4%) and xerosis (2.7%). The
      odds of suffering neck MSD was 10.8 times higher among staff who sat in a chair
      all day (95% CI 1.8-112.8, P < 0.05). Standing all day was also a risk factor for
      this condition (OR 8.2, 95% CI 1.2-81.7, P < 0.05). Female gender increased the
      risk of shoulder MSD 4.3 fold (95% CI 1.4-13.7, P < 0.05), as did alcohol
      consumption (OR 3.3, 95% CI 1.1-11.9, P < 0.05). The odds of suffering any skin
      disease were significantly enhanced by working longer than 12 months in one's
      current job (OR 10.7, 95% CI 1.5-7.3, P < 0.05) and having a history of atopic
      disease (OR 7.2, 95% CI 2.6-21.4, P < 0.001). Overall, the staff within our study
      reported generally lower levels of MSD and skin disease than in previous
      investigations of other workplaces.

PMID- 12506857
TI  - Frequency characteristics of electro-hydraulic vibrator.
AB  - Frequency characteristics of an electro-hydraulic vibrator were measured using
      two kinds of test signals. First, sine signals had theoretically 1.0 m/s2 (root
      mean-square) in the frequency range from 1 to 16 Hz at single axis. The frequency
      characteristics were flat from 1 to 12 Hz, but 14, 16 Hz was considerably poor.
      Second, the vibrator was excited when using a complex signal consisting of 12
      components in the frequency range from 1 to 12 Hz at single axis. The overall
      acceleration was 3 and 1 m/s2. Flat characteristics were seen in the tested
      frequency range. Acceleration distortion was recognized in a higher frequency
      than the target frequency. This second method is effective for the efficiency of
      experimental procedure.

PMID- 12506858
TI  - [Evidence based prevention (EBP): evidence-based approach to prevention of lung
      cancer by application of cytochrome 2E1 polymorphism].
AB  - Most of chemical carcinogens are metabolized and activated in vivo by phase I
      enzymes including the microsomal cytochromes P450 (CYP) and epoxide hydroxylases.
      The carcinogens and their metabolites are detoxified by the phase II enzymes that
      include various transferases such as glutathion-S-transferases (GST). Some
      studies have demonstrated the association of the polymorphisms in CYP2E1 genes
      with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to
      be important biomarkers that provide information for assessments of exposure and
      total burden of environmental carcinogens. Therefore, the investigation of the
      polymorphisms in these genes will provide information not only for the prediction
      of individual cancer risks but also for the prevention of cancer. In this review,
      we will summarize the polymorphisms in the CYP2E1 genes and their relationship to
      the lung cancer susceptibility and prognosis. Gene polymorphisms such as CYP2E1
      will contribute to the evidence based prevention (EBP).

PMID- 12506859
TI  - [A case of hypothyroidism due to hashimoto disease that presented elevations of
      free T3 and free T4 by thyroid hormone autoantibodies].
AB  - When we commonly evaluate the thyroid function, we measure TSH, free T3 and free
      T4. However, there are some cases that are difficult to diagnose because of the
      existence of thyroid hormone autoantibodies. We experienced a case of a 14-year
      old girl with diffuse struma whose TSH, free T3 and free T4 were elevated by
      detected with Amerlex M free T3 and free T4 kits, although she did not have any
      symptoms. As the free T4 level was low by the equilibrium dialysis method, we
      diagnosed this case as hypothyroidism due to chronic thyroiditis. Because we
      found thyroid hormone antibodies in her serum, we thought that this case
      presented pseudoelevations of free T3 and free T4 by the analogue method.

PMID- 12506860
TI  - [The current situation and issues of medical English education and suggestions
      toward improvement--reports from the 5th meeting of the Japan Society for Medical
      English Education].
AB  - This is a report from the 5th academic meeting of the Japan Society for Medical
      English Education held at Kawasaki University of Medical Welfare on August 3rd
      and 4th of 2002. It also includes a course description of our English courses,
      their problems and some suggestions for improvement. First, I report several
      papers presented at the meeting that are useful and suggestive for the English
      education at our university in order to bring them to everyone's attention and to
      improve our English program. The topics of the papers include; what "Medical
      English" is; reports of English courses taught by medical doctors; reports of
      English courses for developing specific proficiencies such as listening, writing
      summaries and delivering oral presentations. Next, I give a course description of
      our present English program and point out some problems that should be dealt
      with. In this connection, I make several suggestions for future improvement.
      Lastly, I refer to the "strategies to educate the Japanese who can use English",
      which were proposed recently by the Ministry of Education, Culture, Sports,
      Science and Technology and suggest our improvement be in line with these
      strategies.

PMID- 12506861
TI  - [Measuring the calibration factor of a light scattering dust monitor for CO2 arc
      welding fumes].
AB  - In Japan, a light scattering type digital dust monitor is most commonly used for
      dust concentration measurement in a working environment. In this study, the
      calibration factors of a digital dust monitor (K-factor) for several welding
      fumes were measured in a laboratory. During the experiment, fumes were generated
      from CO2 arc welding performed by an automatic welding robot. The examined
      welding wires were JIS Z 3312, Z 3313, Z 3315, Z 3317 and Z 3320. The mass and
      relative concentrations of the welding fumes were measured simultaneously by a
      total/respirable (TR) dust sampler and a digital dust monitor at a welding
      current of 100 A, 150 A, 200 A, 250 A and 300 A. The particle size distributions
      of welding fumes were measured by a low pressure impactor at a welding current of
      100 A and 300 A. A significant effect of the welding current on the K-factor was
      recognized for all the examined wires. In the most remarkable case, a four-fold
      difference in the K-factors was found when the fumes were generated from a flux
      cored wire for mild steel (JIS Z 3313). The particle size distributions of fumes
      were also affected by the welding current. The coefficients of variation in the
      measured K-factor were 7.8-40.5%.

PMID- 12506862
TI  - [Report from the 18th UOEH meeting of gastrointestinal image diagnosis].

PMID- 12506863
TI  - The perils of interviral dating.

PMID- 12506864
TI  - Sexual dysfunction and HAART--is there a connection?

PMID- 12506865
TI  - New drugs and drug types boost hope for the future. Report from ICAAC.
AB  - HIV-infected patients who are failing current antiretroviral regimens and their
      clinicians have new cause for hope as HIV researchers are drawing closer to
      bringing some potent new drugs to the market. Entry inhibitors, integrase
      inhibitors, and other new antiretrovirals were highlighted at the 42nd
      Interscience Conference on Antimicrobial Agents and Chemotherapy in San Diego.
      HIV experts call the news very encouraging.

PMID- 12506866
TI  - Depression is common among AIDS patients. Psych consult often is necessary.
AB  - A national survey indicates that it's fairly common for HIV physicians to
      identify depression and similar symptoms in HIV-infected patients. A telephone
      survey of AIDS physicians found that 84.3% reported that their HIV-positive
      patients suffered from depressive symptoms.

PMID- 12506867
TI  - New trend by states is to integrate HIV programs. Collaboration saves some
      resources.
AB  - Until recently, a typical model for providing HIV services has been to separate
      prevention and testing programs from treatment and care programs. While many
      states still adhere to this model, there's a new trend in which state health
      departments are encouraging the two groups to collaborate and even merge their
      boards. The goal is to increase efficiencies, save board members' time, and
      improve communication.

PMID- 12506868
TI  - Computer education may bridge affordability gap. Electronic 'counseling' is easy
      and accessible.
AB  - Researchers at the University of Washington have created and studied a computer
      assisted, client-centered, prevention and education program that they hope will
      encourage risk-reduction behaviors and HIV testing, all on a more affordable
      basis.

PMID- 12506869
TI  - 'Sexual scripts' help MSM discuss safer sex. Intervention study conducted at 13
      sites.
AB  - A CDC-funded community project is teaching young men who have sex with men how to
      discuss and negotiate safer sex. The issue of communicating with partners about
      sex is an important part of an intervention strategy because some preliminary
      findings indicate that young MSM do not consistently include safer-sex
      negotiations and behavior in their 'sexual script'.

PMID- 12506870
TI  - Research raises hope for prevention efforts.

PMID- 12506871
TI  - Adherence tips from down under.

PMID- 12506872
TI  - Finding free or affordable dental services.

PMID- 12506873
TI  - Women's health. Preventative care is the key to healthier living.

PMID- 12506874
TI  - What blocks women with HIV from seeing the dentist?

PMID- 12506875
TI  - Decision on flu vaccine: a shot in the dark?

PMID- 12506876
TI  - Visual event related potentials. The origin of wave P300. A computer model.
AB  - This five-layered model consisting of 180 neurons is aimed at simulating some
      elementary functions of primary visual cortex of mammals in form detection. Its
      main achievements are: 1. Detection of points, lines, simple geometric figures in
      the V1. 2. Abstraction of 19 different qualities of geometric figures. 3.
      Simulation and rational explanation of processing of peripheral stimuli in the
      V1, explanation of mechanism of origin of visual ERPs, including P300 wave. 4.
      Simulation and explanation of the nature and build up of the cognitive function
      within V1 and its possible relation to long-term memory. 5. The model is based
      partly on Hebb-type synapses, illustrates the role of neuronal assemblies, sheds
      light on the functional relationship of excitatory and inhibitory neurons, in
      their conformity with special tasks of different cortical layers.

PMID- 12506877
TI  - Central representation of internal and external sensory information in the CNS of
      Helix pomatia L. and Lymnaea stagnalis L.
AB  - The central representation of intero- and exteroreceptors located in visceral
      organs and the osphradium were compared in the CNS of Helix pomatia L.
      (Gastropoda, Stylommatophora) and Lymnaea stagnalis L. (Gastropoda,
      Basommatophora), two pulmonate snail species inhabiting a terrestrial and
      anaquatic environment, respectively. Semi-intact preparations were used
      comprising the CNS connected by the corresponding nerves either to the cardio
      renal, respiratory and genital systems or to the osphradium. Spike discharges of
      central neurons and the nerves were recorded simultaneously. The central
      representation of intero- and exteroreceptors was found to be distributed
      throughout the CNS and involved about 300 neurons. The majority of the neurons
      received sensory information from all the studied visceral organs and the
      osphradium. Among the neurons responding to intero- and exteroreceptors a
      multimodal reaction to tactile, chemical and osmotic stimuli prevailed while in
      the osphradium specific reactions also were demonstrated. Central neurons
      receiving sensory information from visceral organs and the osphradium form
      overlapping and reorganizing neural circuits using the same neurons in the
      regulation of heart activity, respiration or reproduction producing the
      appropriate behaviour. In the selection of sensory information the firing pattern
      appears to be the main determining factor as bursting neurons do not receive
      sensory information. The central representation of intero- and exteroreceptors
      and its variability can be a model system for cellular studies of motivational
      state and self-perception.

PMID- 12506878
TI  - Bone density in chronic low back pain: a pilot study.
AB  - BACKGROUND AND OBJECTIVE: Levels of physical activity in chronic low back pain
      patients are relatively low due to their fear of provoking pain. This may have a
      secondary impact on maintenance of bone mass. The objective of this study is to
      determine if patients with chronic low back pain are at a higher risk of bone
      demineralization. DESIGN: Bone mineral density (BMD) was measured in 25 chronic
      low back pain patients at the lumbar spine, hip and distal forearm. SETTING: A
      university hospital. SUBJECTS: Twenty-five chronic low back pain patients (mean
      age 45 years) enrolled on a residential back pain rehabilitation programme.
      RESULTS: Thirteen patients (52%) were osteopenic or osteoporotic in one or more
      sites. BMD at the lumbar spine was generally lower than the mean BMD of age
      matched subjects (p = 0.04). There was no significant relationship between BMD
      and duration of pain, disability, sex or previous surgical intervention.
      CONCLUSIONS: Chronic low back pain patients have an increased incidence of
      osteopenia and osteoporosis. This finding reinforces the importance of motivating
      patients to incorporate exercise into daily life. Given the limited set of
      subjects used in the present study, further studies are required.

PMID- 12506879
TI  - Separation of hydrocarbons and lipid from water using treated bark.
AB  - This paper explores the possibility of using treated bark to remove oily
      compounds from water. Bark was first biologically or chemically treated and
      saturated with transition metal ions (TMI) to avoid the release of soluble
      organic compounds from the bark in the treated effluents. Several experimental
      parameters affecting the oil removal efficiency (RE) were studied (initial oil
      concentration, temperature, time, etc.). Saturated bark was characterized using
      Fourier transform infrared (FTIR) spectroscopy and bark wetting index was
      determined. Results of the retention of lipids suggested that their removal could
      exceed 95% of initial oil concentration. The uptake of lipid by treated bark
      varied from 0.2 to 2.0 g of organic oil/g of dry sorbent. No significant chemical
      modifications of saturated bark were observed in infrared spectroscopy after the
      sorption of oleic acid on bark treated with transition metal ions. The structure
      of adsorbed tridimensional layer of oleic acid molecules seemed to take place
      through the double bond. The hydrocarbon RE exceeded 95% using oil-water mixture
      with a hydrocarbon/bark ratio of one. The sorption reaction of hydrocarbons and
      lipids was quasi-instantaneous and seemed to be influenced by the temperature.
      This indicated that the retention mechanism was related to the capillary action.
      Results of FTIR spectroscopy suggested that no chemical bonds between barks and
      oily compounds were established.

PMID- 12506880
TI  - Crystal structure of methyl-3-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)
      propanoate.

PMID- 12506881
TI  - The history and evolution of the ASCI: deja vu all over again. American Society
      for Clinical Investigation.

PMID- 12506882
TI  - Presentation of the Kober Medal to Joseph L. Goldstein and Michael S. Brown.

PMID- 12506883
TI  - Acceptance remarks of Joseph L Goldstein and Michael S. Brown on the occasion of
      the presentation of the Kober Medal, 2002.

PMID- 12506884
TI  - Becker nevus on the hand.

PMID- 12506885
TI  - Urticarial reactions in obstetric transfusion in Maiduguri, north east Nigeria.
AB  - A total of 135 obstetric patients who were first-time transfusion recipients at
      the University of Maiduguri Teaching Hospital were studied with respect to the
      incidence and clinical severity of urticarial transfusion reactions (UTR) in
      relation to the number of previous pregnancies. The overall incidence of UTR was
      12.6%. Analysing the data with respect to the number of previous pregnancies the
      incidence of UTR were 0%, 0%, 3.8%, 8.3%, 21.7% and 37.5% among patients with
      0.1, 2, 3.4 and 5 previous pregnancies respectively. However, all cases of UTR in
      the affected patients were clinically mild, manifesting with urticarial rashes
      and pruritus without any features of anaphylaxis. This data would suggest that
      the risk of UTR increases with the number of previous pregnancies. Therefore,
      multiparous patients need closer observation during transfusion therapy.

PMID- 12506886
TI  - Bullous pemphigoid in a patient with Parkinson's disease.

PMID- 12506887
TI  - Pyogenic granuloma within port-wine stains.

PMID- 12506888
TI  - Efficacy and skin tolerability of saliker in the treatment of dandruff.

PMID- 12506889
TI  - Why study veterinary history.

PMID- 12506890
TI  - Structure of normal human skin.

PMID- 12506891
TI  - Leukocyte trafficking in the skin.

PMID- 12506892
TI  - Molecular control of physiological skin angiogenesis.

PMID- 12506893
TI  - The morphological appearance of facial wrinkles.

PMID- 12506894
TI  - Update on the histological presentation of facial wrinkles.

PMID- 12506895
TI  - Photodamage: pathophysiology - new concepts.

PMID- 12506896
TI  - UV and proteasomes.

PMID- 12506897
TI  - Epidermal and dermal abnormalities.

PMID- 12506898
TI  - Wrinkles - biological and immunological features.

PMID- 12506899
TI  - Perception of wrinkles.

PMID- 12506900
TI  - Effect of an Ajuga turkestanica extract on aquaporin 3 expression, water flux,
      differentiation and barrier parameters of the human epidermis.

PMID- 12506901
TI  - Proteasome: a new target of UV radiations.

PMID- 12506902
TI  - The place, role and importance of veterinary history in the history of sciences,
      culture and arts.

PMID- 12506903
TI  - United unresorbed medial and lateral plicae as anterior mesenchymal synovial
      septal remnant.
AB  - Mesenchymal tissue that forms compartments in the knee joint begins to be
      resorbed in the 8th week of embryologic life. Unless these mesenchymal tissues
      are totally resorbed, they remain as septal remnants, and are termed
      mediopatellar, infrapatellar, suprapatellar, and lateral plicae. We report a case
      of united anterior plica; the inferior part of the anterior mesenchymal septum at
      the back of the patellar tendon was unseparated and unresorbed, and one-half of
      the superior part of the septum beginning from the inferior pole of the patella
      formed the V-shaped medial and lateral plicae such that their opening looked
      upwards.

PMID- 12506904
TI  - The position of history instruction in veterinary curricula.

PMID- 12506905
TI  - Veterinary historiography: a quantitative analysis.

PMID- 12506906
TI  - Comment on T. Bretlau et al., "Bone bruise in acutely injured knee".

PMID- 12506907
TI  - 25 International Symposia and Congresses on the history of veterinary medicine:
      1964-1992; origin and development, themes and trends.

PMID- 12506908
TI  - Addendum on the period 1993-2001 of the congresses on the history of veterinary
      medicine.

PMID- 12506909
TI  - The start and the first 25 years of "Historia Medicinae Veterinariae" (HMV).

PMID- 12506910
TI  - [The use of animals and animal products in therapeutics: an historic view].

PMID- 12506911
TI  - Developmental-behavioral pediatrics.

PMID- 12506912
TI  - Influence of family structure on course of steroid-sensitive nephrotic syndrome.

PMID- 12506913
TI  - Steroid-sensitive nephrotic syndrome and juvenile idiopathic arthritis.

PMID- 12506914
TI  - Distal renal tubular acidosis associated with hypercalcemia and nephrocalcinosis
      in an infant.

PMID- 12506915
TI  - Laparoscopic adjustable gastric band surgery.

PMID- 12506916
TI  - [Animals as sources of medications].

PMID- 12506917
TI  - Ethnoveterinary medicine: an aspect of the history of veterinary medicine.

PMID- 12506918
TI  - Medical and veterinary reports from Colonial Latin America.

PMID- 12506919
TI  - Studies on veterinary manuscripts in Turkey and three samples from the 9th, 12th
      and 14th centuries.

PMID- 12506920
TI  - An analytical approach to the veterinary knowledge of the Islamic period.

PMID- 12506921
TI  - From killing poison to life saving drug: the history behind "blood thinning" in
      thromboembolic diseases.

PMID- 12506922
TI  - Friedrich Loeffler's way to tbe Isle of Riems near Greifswald.

PMID- 12506923
TI  - Antecedents, beginning and development of veterinary education in Hungary.

PMID- 12506924
TI  - [Antibiotics prescription in ambulatory patient].
AB  - OBJECTIVE: To find what antibiotics are prescibed for common infections in adult
      and paediatric primary care patients. DESIGN: Drug utilization (DU) study: cross
      sectional and observational design. SETTING: Primary care centres and hospital
      casualty departments in Bages and Bergueda counties (total population: 198 129
      inhabitants). PARTICIPANTS: Adults and children with acute respiratory infection,
      acute otitis media, acute pharyngitis, acute tonsillitis, or acute bronchitis and
      flu syndrome; adults only with acute sinusitis, attacks of chronic obstructive
      pulmonary disease (COPD) or urinary infections. MAIN MEASUREMENTS AND RESULTS:
      1596 episodes from November 1999 to February 2000 were collected. 975 (61%) of
      these were in adults, and 621 (3996) in children. Of the infections of mainly
      viral aetilogy, those most commonly treated with antibiotics were acute
      Bronchitis, in both adults (76.096 [95% CI, 67.6%-84.2%]) and children (60296
      [95% CI, 50.0%-70.5%]). The most common antibiotics were: amoxycillin/clavulanic
      acid for otitis (34%), sinusitis (37%) and tonsillitis (44%) in adults macrolides
      in attacks of COPD (4096) and tonsillitis (33%) in children; quinolones for
      urinary infections (56%), and cefalor for otitis in children (2096). CONCLUSIONS:
      Local policy measures need to be taken to improve use of antibiotics for primary
      care patients. DU studies are extremely useful, as their description of the
      pattern of prescription enables concrete problems to be detected.

PMID- 12506925
TI  - Life sciences.

PMID- 12506926
TI  - Space colonization.

PMID- 12506927
TI  - Guidelines recommend universal adult depression screening.

PMID- 12506928
TI  - Greater levels of nurse staffing linked to improved clinical outcomes.

PMID- 12506929
TI  - Simple measure predicts how pneumonia patients will fare after discharge.

PMID- 12506930
TI  - Disease management: findings from leading state programs.
AB  - Disease management programs are designed to contain costs by improving health
      among the chronically ill. More than 20 states are now engaged in developing and
      implementing Medicaid disease management programs for their primary care case
      management and fee-for-service populations.

PMID- 12506931
TI  - Guidelines on pain control in seniors favor certain NSAIDs and strategies for the
      cognitively impaired.

PMID- 12506932
TI  - 100 years' tradition and history of successful co-operation between medicine and
      veterinary science in Poland.

PMID- 12506933
TI  - Intermittent atrial fibrillation and stroke.

PMID- 12506934
TI  - Tracking the time-course of attentional involvement in spatial working memory: an
      event-related potential investigation.
AB  - Spatial working memory is a cognitive brain mechanism that enables the temporary
      maintenance and manipulation of spatial information. Recent neuroimaging and
      behavioral studies have led to the proposal that directed spatial attention is
      the mechanism by which location information is maintained in spatial working
      memory. Yet it is unclear whether attentional involvement is required throughout
      the period of active maintenance or is only invoked during discrete task-phases
      such as mnemonic encoding. In the current study, we aimed to track the time
      course of attentional involvement during spatial working memory by recording
      event-related brain potentials (ERPs) from healthy volunteers. In Experiment 1,
      subjects performed a delayed-recognition task. Each trial began with the
      presentation of a brief stimulus (S1) that indicated the relevant location that
      subjects were to maintain in working memory. A 4.8-5.3 sec delay interval
      followed during which a single task-irrelevant probe was presented. The delay
      interval concluded with a test item (S2) to which subjects made a response
      indicating whether the S2-location was the same as the S1-memory location. To
      determine if attention was differentially engaged during discrete phases of the
      trial, task-irrelevant probes were presented early (400-800 msec following S1
      offset) or late (2600-3000 msec following S1-offset) during the delay interval.
      Sensory-evoked ERPs (P1 and N1) elicited by these irrelevant probes showed
      attention-like modulations with greater amplitude responses for probes occurring
      at the S1-memory locations in comparison to probes presented at other locations.
      This pattern was obtained for both early- and late-delay probes. Probe-evoked
      activity during delayed-recognition trials was similar to activity observed when
      spatial attention was explicitly focused on a location in visual space
      (Experiment 2). These results are consistent with a model of spatial working
      memory in which perceptual level selective attention is utilized throughout the
      entire period of active maintenance to keep relevant spatial information in mind.

PMID- 12506935
TI  - Understanding plaque rupture.

PMID- 12506936
TI  - Two views of nitric oxide.

PMID- 12506937
TI  - Linking Chlamydia and heart disease.

PMID- 12506938
TI  - Myocardial perfusion and ACE inhibition.

PMID- 12506939
TI  - Estrogen replacement therapy.

PMID- 12506940
TI  - Beta-blockers for vascular surgery and angioplasty for renal artery stenosis.

PMID- 12506941
TI  - Congenital long QT syndrome.

PMID- 12506942
TI  - Vasopeptidase inhibition in patients with heart failure.

PMID- 12506943
TI  - [3rd Annual Congress of the Croatian Rheumatology Association. Cavtat, 9-11
      November 2001. Proceedings and abstracts].

PMID- 12506945
TI  - Stenting plus abciximab vs tPA in acute myocardial infarction.

PMID- 12506944
TI  - Acute coronary events as a trigger of sudden death in heart failure.

PMID- 12506946
TI  - Incorporation of electron beam CT into routine testing algorithms: do we "just do
      it"?

PMID- 12506947
TI  - Low bone mineral density in cystic fibrosis patients.
AB  - The goals of this practice-based, observational study were to describe the
      prevalence of low bone mineral density in patients at the Edmonton Cystic
      Fibrosis Centre, and to determine if body mass index and previous systemic
      corticosteroid use of over one month's duration were predictors of low bone
      mineral density. One hundred and thirteen pediatric and adult patients were
      studied. Bone mineral density of the lumbar spine region was measured using dual
      energy X-ray absorptiometry. A total of 42.5% of patients had a bone mineral
      density Z-score of less than -1 standard deviation. Low bone mineral density was
      apparent at nine to 12 years of age, and was most evident in the 20- to 34-year
      old group. All but one patient under age 20 with a Z-score of less than -2.5 also
      had a body mass index below the fifth percentile. A low Z-score was also
      associated with previous systemic corticosteroid use of over one month's duration
      (relative risk 1.81, p=0.003). We conclude that low bone mineral density is
      common in cystic fibrosis patients. Low body mass index percentiles may be used
      to identify children and adolescents at risk of low bone mineral density. These
      patients may benefit from aggressive nutrition therapy. Systemic corticosteroid
      use should be assessed carefully, as it is a risk factor for low bone mineral
      density.

PMID- 12506948
TI  - New conjugated pneumococcal vaccine. Does it decrease the incidence of acute
      otitis media? Efficacy of a pneumococcal conjugate vaccine against acute otitis
      media.

PMID- 12506949
TI  - Solving problems, improving practice.

PMID- 12506950
TI  - Comparison of fluconazole and nystatin oral suspensions for treatment of oral
      candidiasis in infants.
AB  - Oral thrush is a common condition in young infants. Nystatin treatment is
      associated with frequent recurrences and difficulty in administration.
      Fluconazole was compared with nystatin for the treatment of oral candidiasis in
      infants. Thirty-four infants were randomized to either nystatin oral suspension
      four times a day for 10 days or fluconazole suspension 3 mg/kg in a single daily
      dose for 7 days. Clinical cures for nystatin were 6 of 19 (32%), and those for
      fluconazole were 15 of 15 (100%), P < 0.0001. In this small pilot study
      fluconazole was shown to be superior to nystatin suspension for the treatment of
      oral thrush in otherwise healthy infants.

PMID- 12506951
TI  - Mumps meningoencephalitis effect on hearing.
AB  - Sensorineural hearing loss is an important complication of mumps. Audiologic
      tests of 26 children with mumps meningoencephalitis, 25 uncomplicated mumps cases
      and 20 control cases were performed, and hearing level thresholds at speech and
      high frequencies were determined. The mean hearing level thresholds in the mumps
      meningoencephalitis group were higher than those of mumps cases at frequencies
      from 6,000 to 18,000 Hz in the right ear and at 250 and from 4,000 to 18,000 Hz
      in the left ear (P < 0.05). Mumps meningoencephalitis cases had higher mean
      hearing thresholds than did control groups at all frequencies other than 125 and
      250 Hz in the right ear and 10,000 Hz in the left ear. The mean hearing
      thresholds of mumps cases were higher than those of control group at frequencies
      of 1,000 and 4,000 Hz in the right ear and 1,000 and 10,000 Hz in the left ear (P
      < 0.05). These results show that mumps meningoencephalitis causes a higher risk
      of hearing loss than does mumps.

PMID- 12506952
TI  - Tuberculosis pyomyosits of the soleus muscle in a fifteen-year-old boy.
AB  - Skeletal muscle infection caused by Mycobacterium tuberculosis is rare and
      usually caused by invasion from adjacent structures. We describe a 15-year-old
      male youth with tuberculous right inguinal lymphadenitis and right calf swelling
      who had tuberculous pyomyositis of the soleus, probably resulting from
      hematogenous seeding. Tuberculosis should be suspected as the cause of
      pyomyositis, especially if present elsewhere.

PMID- 12506953
TI  - Mycoplasma hominis scalp abscess in the newborn.
AB  - Scalp abscess in the newborn is usually a complication of fetal scalp monitoring
      and is typically polymicrobial, reflecting maternal vaginal flora. We present a
      newborn with no apparent scalp trauma who developed scalp abscess that yielded
      pure growth of Mycoplasma hominis. The clue to diagnosis was the growth of
      pinpoint translucent colonies on blood agar that were Gram stain-negative.
      Abscess drainage and systemic clindamycin were curative.

PMID- 12506954
TI  - Recurrent crepitant cellulitis caused by Clostridium perfringens.
AB  - A previously healthy 13-year-old boy developed extensive subcutaneous emphysema
      of the lower limb after a penetrating injury to the knee. Clostridium perfringens
      was isolated from the wound. Despite surgical debridement and appropriate
      antibiotics, the emphysema recurred, and prolonged antibiotic treatment was
      required. This case highlights the distinction between gas gangrene and the
      lesser known entity of clostridial crepitant cellulitis.

PMID- 12506955
TI  - [4th Annual Congress of the Croatian Rheumatology Association. Brijuni, 18-20
      October 2002. Proceedings and abstracts].

PMID- 12506956
TI  - The result of an attempt to find the source of an old Japanese book on equine
      medicine.

PMID- 12506957
TI  - [Oral health in the elderly].

PMID- 12506958
TI  - A diabetes problem solving support group: issues, process and preliminary
      outcomes.
AB  - This report covers the development, process and outcomes of a yearlong diabetes
      problem solving support group. Using the task-centered group work model, the
      participants developed the skills for solving problems of a psychosocial nature.
      Issues, such as the formation of the group, the roles of facilitators and
      members, group process, results, and implications for practice, are discussed.

PMID- 12506959
TI  - Ethical activism: strategies for empowering medical social workers.
AB  - Little empirical research examines the extent medical social workers try to
      change attitudes, norms, expectations, and protocols to create a hospital
      environment that encourages their participation in ethical deliberations. The
      researchers developed an ethical activism scale that measured the extent medical
      social workers engaged in such ethical activism, confirming its reliability from
      data obtained from a sample of 162 medical social workers in 37 hospitals in the
      Los Angeles basin. They tested seven hypotheses that probed the extent specific
      ethics-training, organizational, and demographic variables influence the extent
      social workers engage in ethical activism. Data strongly suggest the need to
      expand ethics training to include tactics of ethical activism, since many social
      workers do not engage in ethical activism. Data also suggest the need to target
      such training to social workers in hospitals that are relatively unreceptive to
      social workers' participation in ethical deliberations, since social workers are
      least likely to engage in ethical activism in such settings.

PMID- 12506960
TI  - Empirically derived guidelines for assessing the psychosocial needs of children
      and adolescents with sickle cell.
AB  - This paper introduces an empirically derived psychosocial assessment form that
      may facilitate the incorporation of the growing body of research on sickle cell
      into the psychosocial assessment process. The psychosocial assessment form was
      guided by two theoretical models that explain the variability in adjustment among
      children and adolescents with sickle cell--the Disability-Stress-Coping Model
      (Wallender, Varni, Babani, Banis, & Wilcox, 1989) and the Transactional Stress
      and Coping Model (Thompson, Gustafson, George Spock, 1994). The Psychosocial
      Assessment Form consists of two sections. The first section includes primary
      indicators of adjustment such as internalizing disorders, externalizing
      disorders, school performance, and difficulties in social relationships. The
      second section lists secondary indicators of adjustment including intrapersonal
      factors, stress processing factors, and social ecological factors. The literature
      that guided this form is also reviewed.

PMID- 12506961
TI  - Cystic fibrosis and the transition to adulthood.
AB  - Cystic fibrosis (CF) has long been thought of as a childhood disease but the life
      expectancy for those with CF has been steadily on the rise and now reaches well
      into adulthood. There has been little or no research on the psychosocial impact
      of CF on becoming an adult. This exploratory, qualitative study examined the
      perceptions of young adults with CF regarding the impact the disease has had on
      their lives, especially during the transition from adolescence to adulthood. The
      findings indicate concerns about health insurance and finances, as well as the
      achievement of independence and optimism for the future.

PMID- 12506962
TI  - Women's experiences with a pregnancy complication: causal explanations of
      hyperemesis gravidarum.
AB  - There is a multiplicity of proposed causes, yet a scarcity of research regarding
      the pregnancy complication, hyperemesis gravidarum (HG), severe nausea and
      vomiting. This is not unlike other female medical conditions that have been
      underinvestigated, and perhaps as a result, erroneous assumptions about them
      persist. This is a report of qualitative findings from a larger study that
      investigated, in part, illness perspectives of 96 women with HG. Results reveal
      women view HG as biologically determined and that it has substantial impact on
      their daily functioning. The study challenges commonly held notions that HG is a
      psychosomatic disorder.

PMID- 12506963
TI  - Social networks of women with undefined musculoskeletal disorder.
AB  - This study was conducted to investigate social integration among, and the
      availability of social support for, female patients with undefined
      musculoskeletal disorder compared to women with coronary heart disease. The aim
      was to elucidate the importance of a clear diagnosis for the social network
      relationships of these female patients. For the measurement of social support two
      instruments were used: an abbreviated version of the Interview Schedule for
      Social Interaction and a condensed version of the Interpersonal Support
      Evaluation List. After adjustment for age, marital and employment status,
      significant differences can be recognized between the two groups of patients: MSD
      patients interact with fewer people and receive less emotional support.
      Implications for social work practice and issues for future research are
      presented.

PMID- 12506964
TI  - Molecular characterization of sucrose:sucrose 1-fructosyltransferase and
      sucrose:fructan 6-fructosyltransferase associated with fructan accumulation in
      winter wheat during cold hardening.
AB  - We isolated two cDNAs of winter wheat (Triticum aestivum L.), designated wft1 and
      wft2, which encoded sucrose:fructan 6-fructosyltransferase (6-SFT) and
      sucrose:sucrose 1-fructosyltransferase (1-SST; EC 2.4.1.99), respectively, which
      are involved in the synthesis of fructan in wheat. wft1 and wft2 were cloned by
      screening of a cDNA library with probed-cDNA fragments corresponding to plant
      fructosyltransferase and invertase. The identity of the clones was verified by
      functional characterization of recombinant proteins expressed in methylotrophic
      yeast, Pichiapastoris. Northern blotting showed that the level of wft2
      transcripts increased from autumn to early winter in the crown tissues of all
      field-grown wheat cultivars examined. Higher levels of wft1 and wft2 transcripts
      were found in leaf tissues of snow mold-resistant cultivars, which accumulated
      more fructan than other cultivars. Our results showed that Wft1 and Wft2 were
      important in fructan accumulation during cold hardening of winter wheat.

PMID- 12506965
TI  - Increasing effect of nori on the fecal excretion of dioxin by rats.
AB  - The effects of nori (Porphyra yezoensis), a kind of red alga, on the
      gastrointestinal absorption and reabsorption of 17 types of dioxin were
      investigated in male Wistar rats. The rats were fed with 4 g of the control diet
      or 4 g of the nori diet containing a standard dioxin solution (233 ngTEQ/kg of
      body weight) for five consecutive days. In the group fed with the 10% nori diet,
      the fecal excretion of dioxin from days 1 to 5 was higher (p<0.01) than that of
      the control group by 5.5-fold for 2,3,7,8-TCDD, 6.6-fold for 1,2,3,7,8-pentaCDD,
      and 6.0-fold for 2,3,4,7,8-pentaCDF. In another experiment, the rats were fed
      with 4 g of the control diet containing a standard dioxin solution (2991 ngTEQ/kg
      of body weight) on the first day of the experiment and then given the control
      diet for 7 consecutive days, before being given either the control diet or the
      nori diet for 28 consecutive days more. In the group fed with the 10% Nori diet,
      the fecal excretion of dioxin during the period from days 8 to 35 was higher
      (p<0.01 or p<0.05) than that of the control group by 2.4-fold for 2,3,7,8-TCDD,
      2.3-fold for 1,2,3,7,8-pentaCDD, and 2.4-fold for 2,3,4,7,8-pentaCDF. These
      results suggest that the administration of nori prevented dioxin from being
      efficiently absorbed and reabsorbed from the gastrointestinal tract, and might be
      useful for protecting humans exposed to dioxin from ill effects.

PMID- 12506966
TI  - Main polyol dehydrogenase of Gluconobacter suboxydans IFO 3255, membrane-bound D
      sorbitol dehydrogenase, that needs product of upstream gene, sldB, for activity.
AB  - The D-sorbitol dehydrogenase gene, sldA, and an upstream gene, sldB, encoding a
      hydrophobic polypeptide, SldB, of Gluconobacter suboxydans IFO 3255 were
      disrupted in a check of their biological functions. The bacterial cells with the
      sldA gene disrupted did not produce L-sorbose by oxidation of D-sorbitol in
      resting-cell reactions at pHs 4.5 and 7.0, indicating that the dehydrogenase was
      the main D-sorbitol-oxidizing enzyme in this bacterium. The cells did not produce
      D-fructose from D-mannitol or dihydroxyacetone from glycerol. The disruption of
      the sldB gene resulted in undetectable oxidation of D-sorbitol, D-mannitol, or
      glycerol, although the cells produced the dehydrogenase. The cells with the sldB
      gene disrupted produced more of what might be signal-unprocessed SldA than the
      wild-type cells did. SldB may be a chaperone-like component that assists signal
      processing and folding of the SldA polypeptide to form active D-sorbitol
      dehydrogenase.

PMID- 12506967
TI  - Recombinant agrobacterium AgaE-like protein with fructosyl amino acid oxidase
      activity.
AB  - Agrobacterium tumefaciens AgaE-like protein had a similar sequence to that of a
      fructosyl amino acid oxidase from Corynebacterium sp. strain 2-4-1. To
      characterize the AgaE-like protein, we produced the enzyme in Escherichia coli,
      and purified it to homogeneity. The molecular mass of recombinant AgaE-like
      protein was 42 kDa on SDS-PAGE and 85 kDa on gel filtration. The protein acted on
      N-fructosyl valine and N-fructosyl glycine as substrates, but not on glycated
      protein or N(epsilon)-fructosyl lysine. Apparent Km for N-fructosyl valine and N
      fructosyl glycine were 1.64 and 0.31 mM, respectively. The AgaE-like protein had
      maximum activity at pH 7.8 and 35 degrees C in 0.1 M potassium phosphate, but
      more than 80% of its activity was lost at 40 degrees C or more. In contrast to
      eukaryotic fructosyl amino acid oxidases, the AgaE-like protein contained
      noncovalently bound FAD as a cofactor and was inactive against N(epsilon)
      fructosyl N(alpha)-Z(benzyloxycarbonyl)-lysine. These characteristics were
      similar to a fructosyl amino acid oxidase from Corynebacterium sp. strain 2-4-1,
      suggesting that these prokaryotic enzymes comprise a new family of fructosyl
      amino acid oxidases.

PMID- 12506968
TI  - Effects of external factors on the interaction of tea catechins with lipid
      bilayers.
AB  - Green tea contains a high concentration of such catechins as (-)-epicatechin
      (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)
      epigallocatechin gallate (EGCg). Their biological activities have been evaluated
      by in vitro experiments using cultured cells or bacteria, but the order of
      activity of the various catechins differed with the study. We have been studying
      the interaction of tea catechins with lipid bilayers, and clarified that the
      number of hydroxyl groups on the B-ring, the presence of the galloyl moiety, and
      the stereochemical structure of each catechin govern their affinity for lipid
      bilayers. We investigated in this present study the effects of various external
      factors on the affinity of tea catechins for lipid bilayers by using liposomes as
      model membranes. The amount of tea catechins incorporated into the lipid bilayers
      increased with increasing salt concentration in an aqueous medium and decreased
      with increasing negative electric charge of the lipid bilayers. Furthermore, the
      amount of EGCg or ECg incorporated into the lipid bilayers increased with
      increasing EC concentration. These results reveal that the salt concentration in
      an aqueous medium, the electric charge of the membrane, and the presence of other
      catechins governed the affinity of tea catechins for the lipid bilayers.

PMID- 12506969
TI  - Antimutagenicity of mono-, di-, and tricaffeoylquinic acid derivatives isolated
      from sweetpotato (Ipomoea batatas L.) leaf.
AB  - The caffeoylquinic acid derivatives, 3-mono-O-caffeoylquinic acid (chlorogenic
      acid, ChA), 3,4-di-O-caffeoylquinic acid (3,4-diCQA), 3,5-di-O-caffeoylquinic
      acid (3,5-diCQA), 4,5-di-O-caffeoylquinic acid (4,5-diCQA) and 3,4,5-tri-O
      caffeoylquinic acid (3,4,5-triCQA), and caffeic acid (CA) were isolated from the
      sweetpotato (Ipomoea batatas L.) leaf. We examined the antimutagenicity of these
      caffeoylquinic acid compounds to promote new uses of the sweetpotato leaf. These
      caffeoylquinic acid derivatives effectively inhibited the reverse mutation
      induced by Trp-P-1 on Salmonella typhimurium TA 98. The antimutagenicity of these
      derivatives was 3,4,5-triCQA > 3,4-diCQA = 3,5-diCQA = 4,5-diCQA > ChA in this
      order. There was no difference in the antimutagenicity of all dicaffeoylquinic
      acid derivatives. A comparison of the activities and structures of these
      compounds suggested that the number of caffeoyl groups bound to quinic acid
      played a role in the antimutagenicity of the caffeoylquinic acid derivatives. The
      sweetpotato leaves contained distinctive polyphenolic components with a high
      content of mono-, di-, and tricaffeoylquinic acid derivatives and could be a
      source of physiological functions.

PMID- 12506970
TI  - Milk calcium taken with cheese increases bone mineral density and bone strength
      in growing rats.
AB  - We investigated the calcium bioavailability of milk calcium, taken with or
      without cheese. Twenty-four 6-week-old male rats for a meal-feeding experiment
      were trained to consume an AIN-76 diet within 2 h (2 times per day) for 2 weeks.
      The rats were then divided into three experimental groups, each fed 2 types of
      experimental diets: Control group, Cheese group, and Ca-Cheese group. The rats
      were each alternately given 2 types of experimental diets at 2-h meal-feeding for
      31 days. The breaking force and energy of the femur in the Ca-Cheese group were
      significantly higher than in the control group. The bone mineral density (BMD) of
      the lumbar spine and the femur in the Ca-Cheese group was also significantly
      higher than in the other two groups. These results indicate that milk calcium
      taken with cheese increases bone strength and BMD efficiently, results that may
      be useful for the prevention of osteoporosis.

PMID- 12506971
TI  - Purification and characterization of a novel cholesterol esterase from
      Pseudomonas aeruginosa, with its application to cleaning lipid-stained contact
      lenses.
AB  - With the aim of developing a new cholesterol esterase for eliminating lipids on
      used contact lenses, microorganisms were screened for the enzyme activity. A
      Pseudomonas aeruginosa isolated from soil was found to produce a desirable
      enzyme. The enzyme had an isoelectric point of 3.2, and molecular mass of 58 kDa.
      The optimal temperature was around 53 degrees C at pH 7.0, and the optimal pH was
      from 5.5 to 9.5. The enzyme was stable between pH 5 and 10 for 19 h at 25 degrees
      C, and retained its activity up to 53 degrees C on 30 min of incubation at pH
      7.0. The rates of hydrolysis of cholesteryl esters of different fatty acids were
      in the following order: linoleate > oleate > stearate > palmitate > caprylate >
      myristate > laurate, caprate > caproate > butyrate, acetate. Addition of
      (tauro)cholate to a final concentration of 100 mM markedly promoted the
      hydrolysis of triglycerides of short-, medium-, and long-chain fatty acids. When
      used with taurocholate, the enzyme acted as an effective cleaner for contact
      lenses stained with lipids consisting of cholesteryl oleate, tripalmitin, and
      stearyl stearate.

PMID- 12506972
TI  - Fusicoccins P and Q, and 3-epifusicoccins H and Q, new polar fusicoccins from
      isolate Niigata 2-A of a peach Fusicoccum canker fungus.
AB  - Our search for new polar fusicoccins biosynthetically related to fusicoccin A
      from the culture filtrate of isolate Niigata 2-A of a peach Fusicoccum canker
      fungus resulted in the isolation of new fusicoccins named fusicoccins P and Q,
      and 3-epifusicoccins H and Q, together with 3'-deacetylfusicoccin A and 16-O
      demethyl-3-epifusicoccin J. The structures of fusicoccins P and Q, and of 3
      epifusicoccin Q were determined to be those of deisopentenylfusicoccin J, 12alpha
      hydroxyfusicoccin H and 12alpha-hydroxy-3-epifusicoccin H, respectively, by NMR
      spectrometry and chemical derivation from known fusicoccins. 3-Epifusicoccin H
      was identified by comparing its 400 MHz NMR spectra with those of fusicoccin H.
      The lettuce seed germination-stimulating activity of these new fusicoccins was
      examined in the presence of ABA: fusicoccin P was highly active, while 3
      epifusicoccins H and Q were slightly active, and fusicoccins H and Q were almost
      inactive. Possible biosynthetic pathways incorporating these new fusicoccins and
      3-epifusicoccins from geranylgeranyl diphosphate to 3'-deacetlyfusicoccin A and
      16-O-demethyl-3-epifusicoccin J are discussed.

PMID- 12506973
TI  - Cloned cytosine deaminase gene expression of Bifidobacterium longum and
      application to enzyme/pro-drug therapy of hypoxic solid tumors.
AB  - Bifidobacterium longum is a nonpathogenic anaerobic bacterium among normal
      bacterial flora. Recently, it was reported that B. longum accumulated in hypoxic
      solid tumors. The gene of interest was expressed in transfected B. longum by the
      shuttle vector pBLES100 in solid tumors. In this report, we constructed pBLES100
      S-eCD, which included the cytosine deaminase gene. We confirmed by western
      blotting that transfected B. longum produced cytosine deaminase. In addition,
      transfected B. longum produced cytosine deaminase that converted 5-fluorocytosine
      into 5-fluorouracil. B. longum could be useful for enzyme/pro-drug therapy of
      hypoxic solid tumors.

PMID- 12506974
TI  - Stable form of ascorbate peroxidase from the red alga Galdieria partita similar
      to both chloroplastic and cytosolic isoforms of higher plants.
AB  - Depletion of the electron donor ascorbate causes rapid inactivation of
      chloroplastic ascorbate peroxidase (APX) of higher plants, while cytosolic APX is
      stable under such conditions. Here we report the cloning of cDNA from Galdieria
      partita, a unicellular red alga, encoding a novel type of APX (APX-B). The
      electrophoretic mobility, Km values, kcat and absorption spectra of recombinant
      APX-B produced in Escherichia coli were measured. Recombinant APX-B remained
      active for at least 180 min after depletion of ascorbate. The amino-terminal half
      of APX-B, which forms the distal pocket of the active site, was richer in amino
      acid residues conserved in chloroplastic APXs of higher plants rather than
      cytosolic APXs. In contrast, the sequence of the carboxyl-terminal half, which
      forms the proximal pocket, was similar to that of the cytosolic isoform. The
      stability of APX-B might be due to its cytosolic isoform-like structure of the
      carboxyl-terminal half.

PMID- 12506975
TI  - Bilirubin dehydrogenase, an enzyme in Aspergillus ochraceus IB-3 useful for
      diagnostic measurement of bilirubin.
AB  - Bilirubin dehydrogenase, a membrane-bound enzyme that catalyzes the one-step
      oxidation of ditaurobilirubin and bilirubin to ditaurobiliverdin and biliverdin,
      respectively, in the presence of an electron acceptor, was found in Aspergillus
      ochraceus IB-3, and purified from the membrane fraction through solubilization by
      Triton X-100. Phenazine and quinone derivatives acted as electron acceptors.
      Accumulation of ditaurobiliverdin and biliverdin by enzyme catalysis increased
      the absorbance at 660 nm, which is far from the range of wavelengths affected by
      serum ingredients. The enzyme selectively oxidized ditaurobilirubin at low pH, so
      changes in the reaction pH enable the enzyme to discriminate between the
      bilirubin fractions ditaurobilirubin (an example of conjugated bilirubin) and
      bilirubin (an example of unconjugated bilirubin). Using the enzyme, 2 to 80
      microM of ditaurobilirubin were measured accurately by monitoring the changes in
      absorbance at 660 nm.

PMID- 12506976
TI  - Equilibrium dialysis measurements of the Ca2+-binding properties of recombinant
      radish vacuolar Ca2+-binding protein expressed in Escherichia coli.
AB  - Vacuoles of radish (Raphanus sativus) contained a Ca2+-binding protein (RVCaB) of
      43 kDa. We investigated the Ca2+-binding properties of the protein. RVCaB was
      expressed in Escherichia coli and was purified from an extract by ion-exchange
      chromatography, nitrocellulose membrane filtration, and gel-filtration column
      chromatography. Ca2+-binding properties of the recombinant protein were examined
      by equilibrium dialysis with 45Ca2+ and small dialysis buttons. The protein was
      estimated to bind 19Ca2+ ions per molecule with a Kd for Ca2+ of 3.4 mM. Ca2+ was
      bound to the protein even in the presence of high concentrations of Mg2+ or K+.
      The results suggested that the protein bound Ca2+ with high ion selectivity, high
      capacity, and low affinity.

PMID- 12506977
TI  - Novel reversible indole-3-carboxylate decarboxylase catalyzing nonoxidative
      decarboxylation.
AB  - After enrichment culture with indole-3-carboxylate in static culture, a novel
      reversible decarboxylase, indole-3-carboxylate decarboxylase, was found in
      Arthrobacter nicotianae FI1612 and several molds. The enzyme reaction was
      examined in resting-cell reactions with A. nicotianae FI1612. The enzyme activity
      was induced specifically by indole-3-carboxylate, but not by indole. The indole-3
      carboxylate decarboxylase of A. nicotianae FI1612 catalyzed the nonoxidative
      decarboxylation of indole-3-carboxylate into indole, and efficiently carboxylated
      indole and 2-methylindole by the reverse reaction. In the presence of 1 mM
      dithiothreitol, 50 mM Na2 S2O3, and 20% (v/v) glycerol, indole-3-carboxylate
      decarboxylase was partially purified from A. nicotianae FI1612. The purified
      enzyme had a molecular mass of approximately 258 kDa. The enzyme did not need any
      cofactor for the decarboxylating and carboxylating reactions.

PMID- 12506978
TI  - Identification of the bile acid-binding region in the soy glycinin A1aB1b
      subunit.
AB  - Soy glycinin has five major subunits which are classified into two groups
      according to their homology in amino acid sequences (group I, A1aB1b, A1bB2 and
      A2B1a; group II, A3B4 and A5A4B3). It has been reported that the peptide
      fragments derived from the A1a and A2 chains of the A1aB1b and A2B1a subunits had
      bile acid-binding ability and that the region of 114-161 residues of the A1a
      chain was responsible for this bile acid-binding ability. In this study, we
      constructed A1a, A3 and 9 deletion mutants of A1a lacking various numbers of
      residues at the C-terminus, and evaluated their bile acid-binding ability by a
      cholic acid-conjugated column and fluorescence analysis. The bile acid-binding
      ability of A1a was higher than that of A3 and there was a remarkable decrease in
      the bile acid-binding ability between the delta[138-291] and delta[130-291]
      mutants. The 130-138 region is rich in hydrophobic residues. In this regard, when
      we constructed the delta[129-134] mutant lacking six contiguous hydrophobic
      residues (VAWWMY) and evaluated its bile acid-binding ability, a similar
      remarkable decrease in the bile acid-binding ability was observed. These results
      indicate that the 129-134 residue region (VAWWMY) with high hydrophobicity was
      important for bile acid-binding of A1a.

PMID- 12506979
TI  - Epitope analysis of antibodies in Japanese to human cytomegalovirus
      phosphoprotein 150 with synthetic peptides.
AB  - Serological detection of antibodies specific to human cytomegalovirus (HCMV) is
      not reliable because the assay uses the whole HCMV protein fraction. Antigenic
      materials composed of well-characterized viral proteins are being tried for
      serodiagnosis in Europe. Epitopes of antibodies to HCMV phosphoprotein 150
      (pp150) encoded by UL32 in Japanese individuals were investigated for comparison
      with the results in Europe. The major epitopes on amino acid residues 496 to 652
      of HCMV pp150 were identified and the detection of antibodies with an enzyme
      linked immunosorbent assay (ELISA) of synthetic peptides against the main
      epitopes was established. Fifteen seropositive and five seronegative serum
      samples for the epitope mapping and 131 seropositive and 50 seronegative samples
      for ELISA were investigated. Overlapping 15-mer peptides moving by two amino
      acids through V496-H652 were synthesized. The main epitope regions were V508
      D530, L526-Q544, S536-D554, T616-G634, S624-P642, and L632-H652. When each
      peptide was conjugated with bovine serum albumin for ELISA, 80.9% of the
      seropositive samples were judged to be positive. The results of this study are
      the same as those for European sera, so the antigenic materials developed in
      Europe might be used to replace the whole HCMV protein fraction in Japanese.

PMID- 12506980
TI  - Synthesis and insecticidal activity of N-oxydihydropyrroles: 4-hydroxy-3-mesityl
      5,5-dimethyl derivatives with various substituents at the 1-position.
AB  - A new series of N-oxydihydropyrrole derivatives was synthesized and evaluated for
      insecticidal activity against Nilaparvata lugens and Myzus persicae. Various
      substituents were introduced to the 1-position of the dihydropyrrole ring, and
      the derivatives obtained exhibited systemic and/or contact insecticidal activity.
      The structure-activity relationship revealed that small alkyoxy and alkoxyalkoxy
      groups were more favorable than alkylcarbonyloxy, alkoxycarbonyloxy, or
      sulfonyloxy groups as substituents at the 1-position.

PMID- 12506981
TI  - Purification and characterization of a novel fungal alpha-glucosidase from
      Mortierella alliacea with high starch-hydrolytic activity.
AB  - The fungal strain Mortierella alliacea YN-15 is an arachidonic acid producer that
      assimilates soluble starch despite having undetectable alpha-amylase activity.
      Here, a alpha-glucosidase responsible for the starch hydrolysis was purified from
      the culture broth through four-step column chromatography. Maltose and other
      oligosaccharides were less preferentially hydrolyzed and were used as a glucosyl
      donor for transglucosylation by the enzyme, demonstrating distinct substrate
      specificity as a fungal alpha-glucosidase. The purified enzyme consisted of two
      heterosubunits of 61 and 31 kDa that were not linked by a covalent bond but
      stably aggregated to each other even at a high salt concentration (0.5 M), and
      behaved like a single 92-kDa component in gel-filtration chromatography. The
      hydrolytic activity on maltose reached a maximum at 55 degrees C and in a pH
      range of 5.0-6.0, and in the presence of ethanol, the transglucosylation reaction
      to form ethyl-alpha-D-glucoside was optimal at pH 5.0 and a temperature range of
      45-50 degrees C.

PMID- 12506982
TI  - Repellents in the Japanese cedar, Cryptomeria japonica, against the pill-bug,
      Armadillidium vulgare.
AB  - Sandaracopimarinol and (1S,6R)-2,7(14),10-bisabolatrien-1-ol-4-one were isolated
      and identified from Cryptomeria japonica as repellents against Armadillidium
      vulgare which is well known as an unpleasant pest in the house and as vegetable
      pest in Japan. These compounds strongly repelled A. vulgare when they were
      combined, although each compound alone did not show any activity.

PMID- 12506983
TI  - Compilation and characterization of a novel WNK family of protein kinases in
      Arabiodpsis thaliana with reference to circadian rhythms.
AB  - The complete genome sequence of Arabidopsis thaliana revealed that this higher
      plant has a tremendous number of protein kinases. We recently isolated a novel
      type of protein kinase, named AtWNK1, which shows an in vitro ability to
      phosphorylate the APRR3 member of the APRR1/TOC1 quintet that has been implicated
      in a mechanism underlying circadian rhythms in Arabidopsis. We here address two
      issues, one general and one specific, as to this novel protein kinase. We first
      asked the general question of how many WNK family members are present in this
      higher plant, then whether or not other members are also relevant to circadian
      rhythms. The results of our analyses showed that Arabidopsis has at least 9
      members of the WNK1 family of protein kinases (designated here as WNK1 to WNK9),
      the structural design of which is clearly distinct from those of other known
      protein kinases, such as receptor-like kinases and mitogen-activated protein
      kinases. They were examined with special reference to the circadian-related
      APRR1/TOC1 quintet. It was found that not only the transcription of the WNK1
      gene, but also those of three other members (WNK2, WNK4, and WNK6) are under the
      control of circadian rhythms. These results suggested that certain members of the
      WNK family of protein kinases might play roles in a mechanism that generates
      circadian rhythms in Arabidopsis.

PMID- 12506984
TI  - Effects of partial suppression of ribosomal protein S6 on organ formation in
      Arabidopsis thaliana.
AB  - An expression library of Arabidopsis thaliana cDNAs was randomly introduced into
      A. thaliana. The transformant pool was used to obtain a line, c105, with reduced
      apical dominance and irregular positioning of leaves and flowers. The inserted
      DNA was a 3'-fragment of the ribosomal protein S6 gene with antisense
      orientation. The transcriptional level of the ribosomal protein S6 was lower in
      c105 than in the wild-type plant. Introduction of the same fragment into the wild
      type plant gave phenotypes similar to those of c105, so the phenotypes of c105
      were due to the S6 antisense expression. The phenotypes suggest selectively
      reduced function of specific proteins rather than an overall decrease in protein
      function caused by defective ribosomal biogenesis.

PMID- 12506985
TI  - Paecilopeptin, a new cathepsin S inhibitor produced by Paecilomyces carneus.
AB  - Paecilopeptin, a novel cathepsin S inhibitor, was produced and isolated from the
      culture supernatant of the fungal strain, Paecilomyces carneus. A spectroscopic
      analysis revealed the planar structure of paecilopeptin to be acetyl-Leu-Val-CHO.
      The stereochemistry of the constituent amino acids was analysed by chiral HPLC
      after oxidation and 6N HCl hydrolysis of paecilopeptin. The total synthesis of
      paecilopeptin was completed in six steps. Paecilopeptin inhibited human cathepsin
      S with an IC50 value of 2.1 nM in vitro.

PMID- 12506986
TI  - Transepithelial transport of fluorescein in Caco-2 cell monolayers and use of
      such transport in in vitro evaluation of phenolic acid availability.
AB  - Fluorescein is a marker-dye customary applied to the evaluation of tight
      junctional permeability of epithelial cell monolayers. However, the true
      mechanism for the permeation has not been elucidated. Transepithelial transport
      of fluorescein in Caco-2 cell monolayers was therefore examined. Fluorescein
      transport was dependent on pH, and in a vectorical way in the apical-basolateral
      direction, but it was independent of the tight-junctional permeability of
      monolayers of these human intestinal cells. The permeation of fluorescein was
      concentration-dependent and saturable; the Michaelis constant was 7.7 mM and the
      maximum velocity was 40.3 nmol min(-1) (mg protein)(-1). Benzoic acid
      competitively inhibited fluorescein transport, suggesting that fluorescein is
      transported by a monocarboxylic acid transporter (MCT). Antioxidative
      polyphenolic compounds such as ferulic acid from dietary sources, competitively
      inhibited the permeation of fluorescein. These compounds probably share a
      transport carrier with fluorescein. Measurement of the effects of phenolic acids
      on fluorescein transport across Caco-2 monolayers would be a useful way to
      evaluate the intestinal absorption or bioavailability of dietary phenolic acids.

PMID- 12506987
TI  - Biotransformation of (-)-verbenone by human liver microsomes.
AB  - The biotransformation of (-)-verbenone was investigated with human liver
      microsomes by using GC-MS. Regioselective biotransformation was observed when (-)
      verbenone was incubated with the liver microsomes. (-)-10-Hydroxyverbenone was
      formed from (-)-verbenone of kinetic analysis showed that the Km and Vmax values
      for the hydroxylation of (-)-verbenone by liver microsomes from three human
      samples, HG-70, HG-56 and HG-23, were 1.1 mM and 4.8 nmol/min/nmol P450, 0.6 mM
      and 2.1 nmol/min/nmol P450, and 2.8 mM and 4.6 nmol/min/nmol P450, respectively.

PMID- 12506988
TI  - Identification of the sex pheromone components secreted by female moths of
      Peridroma saucia (Noctuidae: Noctuinae).
AB  - The variegated cutworm, Peridroma saucia Hubner, is a lepidopteran pest to a
      large number of crops in Canada, the United States, and Europe. It was probably
      naturalized in Japan in the 1970s. The pheromone glands of the female moth
      include two components with electroantennographic activity in a ratio of 3:1. GC
      MS analyses of pheromone extracts untreated and treated with dimethyl disulfide
      revealed the major component to be (Z)-11-hexadecenyl acetate and the minor
      component to be (Z)-9-tetradecenyl acetate. The synthetic pheromone was used to
      attract a large number of males in a vegetable field in Tokyo, which suggests
      that this species has already become a harmful pest in Japan.

PMID- 12506989
TI  - Influence of dietary methionine level on the liver metallothionein mRNA level in
      rats.
AB  - The effects of some methyl-containing compounds added to a choline-deficient diet
      on the metallothionein mRNA level in the rat liver were studied. The addition of
      choline or carnitine to the choline-deficient diet did not induce a gain in body
      weight, while the addition of either betaine or methionine to the choline
      deficient diet, or of methionine to the choline-deficient diet with choline
      significantly increased the body weight. The metallothionein mRNA level in the
      liver of rats fed on the choline-deficient diet was similar to that of rats fed
      on the choline-deficient diet with choline, betaine or carnitine. However, the
      addition of methionine to the choline-deficient diet with or without choline
      caused a marked suppression in the metallothionein mRNA level in the liver. It is
      thus surmised that the metallothionein mRNA level in the liver might be regulated
      by the dietary content of methionine.

PMID- 12506990
TI  - Siderophore production and induction of iron-regulated proteins by a
      microorganism from rhizosphere of barley.
AB  - This study provides new information on the Fe uptake system capable of supporting
      growth of the organism. Pseudomonas fluorescens isolated from the rhizosphere of
      barley, a gramineous plant, produced a siderophore under iron-limiting
      conditions. Its chemical structure was identified as pyochelin, on the basis of
      1H and 13C NMR data of a stable methyl ester derivative. The same iron-limiting
      conditions induced a new set of outer membrane proteins (75 and 55 kDa),
      consistent with a siderophore-mediated iron-uptake system.

PMID- 12506991
TI  - Characterization of five phyllosphere bacteria isolated from Rosa rugosa leaves,
      and their phenotypic and metabolic properties.
AB  - Five gram-negative bacteria, all of which were Enterobacteriaceae, were isolated
      from the phyllosphere of green or senescing leaves of Rosa rugosa, and their
      phenotypic and physiological characteristics were examined. Partial 16S rDNA
      sequences led to identification of these isolates as Pantoea agglomerans,
      Klebsiella terrigena, Erwinia rhapontici, and two strains of Rahnella aquatilis.
      Interestingly, these phyllosphere bacteria had certain phenotypic and
      physiological convergences, while they showed their own metabolic properties
      toward phenolic compounds of plant origin. In particular, the two Ra. aquatilis
      isolates from the green leaves had a substrate-inducible gallate decarboxylase
      activity in the resting cells that had been cultured in 1 mM gallic acid- or
      protocatechuic acid-containing medium. The other three isolates from the
      senescing leaves did not have this enzyme activity. Simple phenolics that the Ra.
      aquatilis decarboxylatively produced from benzoic acid derivatives had better
      antimicrobial activities than those of the substrates.

PMID- 12506992
TI  - Carotenoid pigments in GAC fruit (Momordica cochinchinensis SPRENG).
AB  - The carotenoids in Gac fruit (Momordica Cochinchinensis spreng) were analysed by
      high-performance liquid chromatography (HPLC), and the concentrations of beta
      carotene, lycopene, zeaxanthin and beta-cryptoxanthin were measured. Lycopene was
      found to be predominantly present in the Gac seed membrane at a concentration of
      up to 380 microg/g of seed membrane. The concentration of lycopene in the Gac
      seed membrane was about ten-fold higher than that in known lycopene-rich fruit
      and vegetables, indicating that Gac fruit could be a new and potentially valuable
      source of lycopene.

PMID- 12506993
TI  - Anthocyanin compositions in sweetpotato (Ipomoea batatas L.) leaves.
AB  - The anthocyanin composition of three varieties, Simon No. 1, Kyushu No. 119, and
      Elegant Summer, in sweetpotato (Ipomoea batatas L.) leaves was examined for
      promoting new uses. Fifteen anthocyanin compounds were identified and measured.
      HPLC clearly showed quantitative differences, but not qualitative ones. The
      anthocyanins were acylated cyanidin and peonidin type. The result suggests that
      the major anthocyanin composition of sweetpotato leaves is cyanidin type.

PMID- 12506994
TI  - Identification of a wheat allergen, Tri a Bd 36K, as a peroxidase.
AB  - A 36-kDa allergen, Tri a Bd 36K, was purified from wheat albumin and
      characterized. The protein was similar to barley peroxidase BP-1 both in its
      amino acid sequence and peroxidase activity. The enzyme seemed to contain L
      fucose and D-mannose and the glycan moiety reacted with IgE antibodies in a
      patient's serum.

PMID- 12506995
TI  - Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by a
      Coptidis Rhizoma extract and protoberberine alkaloids.
AB  - A methanol extract of Coptidis Rhizoma effectively enhanced the outgrowth of
      neurite in PC12 cells induced by nerve growth factor (NGF). Following solvent
      partition and preparative HPLC, berberine was isolated as the major active
      compound. Berberine enhanced the proportion of neurite-bearing cells in a dose
      dependent manner without cytotoxicity. Its structural relatives, palmatine and
      coptisine, showed a slightly weaker NGF-enhancing effect than berberine. These
      three alkaloids inhibited acetylcholinesterase activity at a level comparable to
      that of physostigmine, but this inhibition was not responsible for the
      potentiation of NGF-induced neurite outgrowth. It is demonstrated for the first
      time that protoberberine alkaloids potentiated the NGF-induced differentiation of
      neural cells.

PMID- 12506996
TI  - Isolation and characterization of cDNAs that encode homologs of a pathogenesis
      related protein allergen from Cryptomeria japonica.
AB  - Many plant pathogenesis-related (PR) proteins are allergenic. We isolated three
      cDNAs, Cry j 3.1, Cry j 3.2, and Cry j 3.3, that encoded homologs of Jun a 3, a
      PR protein allergen in Juniperus ashei, from a cDNA library derived from the
      pollen of Cryptomeria japonica. The predicted amino acid sequences encoded by the
      three cDNAs were more than 85% identical to each other and about 57% identical to
      the sequence of Jun a 3. The Cry j 3 genes seemed to form a small multigene
      family in the genome of C. japonica. Expression of Cry j 3 was strong in roots
      and in female and male strobili; expression was weaker in cotyledons, leaves,
      stems, and pollen grains.

PMID- 12506997
TI  - Synthesis of both enantiomers of isorobinal, a novel cyclic monoterpene isolated
      from the astigmatid mite, Rhizoglyphus sp.
AB  - Both enantiomers of isorobinal, a cyclic monoterpene isolated from the astigmatid
      mite (Rhizoglyphus sp.), were synthesized from the enantiomers of perillaldehyde
      in four steps by using PCC-oxidation of a tertiary allylic alcohol intermediate
      as the key step.

PMID- 12506998
TI  - Total synthesis of (+/-)-syn-copalol.
AB  - The labdane diterpene derivative, syn-copalol [(+)-5] is the alcohol part of syn
      copalyl diphosphate [(+)-4]. In this paper, racemic (+/-)-5 was synthesized from
      a known racemic lactone in 8 steps. The current and our previous syntheses
      provide all four copalol derivatives [(+)-3, (-)-3 and (+/-)-5] which are
      required for the biosynthetic study of polycyclic diterpenes.

PMID- 12506999
TI  - Molecular cloning and mRNA expression of geraniol-inducible genes in cultured
      shoot primordia of Matricaria chamomilla.
AB  - Genes for two geraniol-responsive factors, designated McEREBP1 and McWRKY1, from
      cultured shoot primordia of Matricaria chamomilla were cloned. The deduced amino
      acid sequences of these genes were highly similar to those of the family of
      ethylene-responsive element binding proteins and elicitor-induced DNA-binding
      proteins containing a WRKY domain, respectively. The levels of McEREBP1 and
      McWRKY1 mRNAs were maximum when measured 1 h after treatment of the cultured
      cells with geraniol.

PMID- 12507000
TI  - Purification and characterization of beta-1,6-glucanase of Streptomyces rochei
      application in the study of yeast cell wall proteins.
AB  - A beta-1,6-glucanase was purified to apparent homogeneity from a commercial yeast
      digestive enzyme prepared from Streptomyces rochei by a series of column
      chromatographies. The molecular mass of the purified enzyme was 60 kDa by SDS
      PAGE. The purified enzyme had an optimum pH range from 4.0 to 6.0 and was stable
      in the same pH range. The enzyme was stable under 50 degrees C but lost almost
      all activity at 60 degrees C. The enzyme was specific to beta-1,6-glucan and had
      little activity towards beta-1,3-glucan and beta-1,4-glucan. When the beta-1,6
      glucan was hydrolyzed with the purified enzyme for 5 h, the reaction products
      contained 20% glucose, 36% gentiobiose, and 44% other oligosaccharides,
      suggesting that the enzyme is an endo-type glucanase. When the purified enzyme
      was used for the digestion of the cell wall of Saccharomyces cerevisiae, cell
      wall proteins covalently bound to the cell-wall glucan were recovered as soluble
      forms, suggesting that this enzyme is useful for analysis of yeast-cell wall
      proteins.

PMID- 12507001
TI  - Mutual binding inhibition of tetrodotoxin and saxitoxin to their binding protein
      from the plasma of the puffer fish, Fugu pardalis.
AB  - The mutual binding inhibition of tetrodotoxin and saxitoxin to their binding
      protein from the plasma of Fugu pardalis was investigated by HPLC. The values for
      the half inhibitory concentration of tetrodotoxin (1.6 microM) binding to this
      protein (1.2 microM) for saxitoxin, and of saxitoxin (0.47 microM) binding to
      that (0.30 microM) for tetrodotoxin were 0.35 +/- 0.057 microM and 81 +/- 16
      microM (n = 2), respectively.

PMID- 12507002
TI  - Categorization, concept learning, and behavior analysis: an introduction.
AB  - Categorization and concept learning encompass some of the most important aspects
      of behavior, but historically they have not been central topics in the
      experimental analysis of behavior. To introduce this special issue of the Journal
      of the Experimental Analysis of Behavior (JEAB), we define key terms; distinguish
      between the study of concepts and the study of concept learning; describe three
      types of concept learning characterized by the stimulus classes they yield; and
      briefly identify several other themes (e.g., quantitative modeling and ties to
      language) that appear in the literature. As the special issue demonstrates, a
      surprising amount and diversity of work is being conducted that either represents
      a behavior-analytic perspective or can inform or constructively challenge this
      perspective.

PMID- 12507003
TI  - Categorizing a moving target in terms of its speed, direction, or both.
AB  - Pigeons categorized a moving target in terms of its speed and direction in an
      adaptation of the randomization procedure used to study human categorization
      behavior (Ashby & Maddox, 1998). The target moved according to vectors that were
      sampled with equal probabilities from two slightly overlapping bivariate normal
      distributions with the dimensions of speed and direction. On the average, pigeons
      categorized optimally in that they attended to either speed or direction alone,
      or divided attention between them, as was required by different reinforcement
      contingencies. Decision bounds were estimated for individual pigeons for each
      attentional task. Average slopes and y intercepts of these individually estimated
      decision bounds closely approximated the corresponding values for optimal
      decision bounds. There is therefore at least one task in which pigeons, on the
      average, display flexibility and quantitative precision in allocating attention
      to speed and direction when they categorize moving targets.

PMID- 12507004
TI  - The formation of linked perceptual classes.
AB  - Multiple-exemplar training with stimuli in four domains induced two new fill
      based (A1' and A2') and satellite-image-based (B1' and B2') perceptual classes.
      Conditional discriminations were established between the endpoints of the A1' and
      B1' classes as well as the A2' and B2' classes. The emergence of linked
      perceptual classes was evaluated by the performances occasioned by nine cross
      class probes that contained fill variants as samples and satellite variants as
      comparisons, along with nine other cross-class probes that consisted of satellite
      variants as samples and fill variants as comparisons. The 18 probes were first
      presented serially and then concurrently. Class-consistent responding indicated
      the emergence of linked perceptual classes. Of the linked perceptual classes, 70%
      emerged during the initial serial test. An additional 20% of the linked
      perceptual classes emerged during the subsequently presented concurrent test
      block. Thus, linked perceptual classes emerged on an immediate or delayed basis.
      Linked perceptual classes, then, share structural and fuctional similarities with
      equivalence classes, generalized equivalence classes, cross-modal classes, and
      complex maturally occurring categories, and may clarify processes such as
      intersensory perception.

PMID- 12507005
TI  - The formation of a generalized categorization repertoire: effect of training with
      multiple domains, samples, and comparisons.
AB  - The present experiment explored the effects of three variables on the spontaneous
      categorization of stimuli in perceptually distinct and novel domains. Each of six
      stimulus domains was created by morphing two images that were the domain
      endpoints. The endpoints of the domains were male and female faces, two abstract
      drawings, a car and a truck, two banded-elevation satellite land images, a tree
      and a cat, and two false-color satellite images. The stimulus variants at each
      end of a domain defined two potential perceptual classes. Training was conducted
      in a matching-to-sample format and used stimuli from one or two domains, one or
      three variants per class as samples, and one or three variants per class as
      comparisons. The spontaneous categorization of stimuli in the untrained stimulus
      domains showed the emergence of a generalized categorization repertoire. The
      proportion of spontaneously categorized stimuli in the new domains was positively
      related to the number of domains and samples used in training, and was inversely
      related to the number of comparisons used in training. Differential reaction
      times demonstrated the discriminability of the stimuli in the emergent classes.
      This study is among the first to provide an empirical basis for a behavior
      analytic model of the development of generalized categorization repertoires in
      natural settings.

PMID- 12507006
TI  - Natural concepts in a juvenile gorilla (gorilla gorilla gorilla) at three levels
      of abstraction.
AB  - The extent to which nonhumans are able to form conceptual versus perceptual
      discriminations remains a matter of debate. Among the great apes, only
      chimpanzees have been tested for conceptual understanding, defined as the ability
      to form discriminations not based solely on simple perceptual features of
      stimuli, and to transfer this learning to novel stimuli. In the present
      investigation, a young captive female gorilla was trained at three levels of
      abstraction (concrete, intermediate, and abstract) involving sets of photographs
      representing natural categories (e.g., orangutans vs. humans, primates vs.
      nonprimate animals, animals vs. foods). Within each level of abstraction, when
      the gorilla had learned to discriminate positive from negative exemplars in one
      set of photographs, a novel set was introduced. Transfer was defined in terms of
      high accuracy during the first two sessions with the new stimuli. The gorilla
      acquired discriminations at all three levels of abstraction but showed
      unambiguous transfer only with the concrete and abstract stimulus sets. Detailed
      analyses of response patterns revealed little evidence of control by simple
      stimulus features. Acquisition and transfer involving abstract stimulus sets
      suggest a conceptual basis for gorilla categorization. The gorilla's relatively
      poor performance with intermediate-level discriminations parallels findings with
      pigeons, and suggests a need to reconsider the role of perceptual information in
      discriminations thought to indicate conceptual behavior in nonhumans.

PMID- 12507007
TI  - Failure to find evidence of stimulus generalization within pictorial categories
      in pigeons.
AB  - Pigeons' key pecks were reinforced in the presence of pictures from one of two
      categories, cats or cars. A single picture associated with reinforcement was used
      in Experiment 1, and 20 pictures from the same category were associated with
      reinforcement in Experiment 2. Pigeons then were presented with novel test
      pictures from the training category and from the other, previously unseen,
      category. During Session 1 of testing, pigeons pecked no more often at pictures
      from the reinforced category than at pictures from the previously unseen
      category. When pigeons were trained with pictures associated with reinforcement
      or its absence from different categories in Experiment 3, differential responding
      to novel pictures from different categories appeared during Session 1. These
      findings argue against a process of automatic stimulus generalization within
      natural categories and in favor of the position that category distinctions are
      not made until members of at least two categories are compared with one another.

PMID- 12507008
TI  - The structure of pigeon multiple-class same-different learning.
AB  - Three experiments examined the structure of the decision framework used by
      pigeons in learning a multiple-class same-different task. Using a same-different
      choice task requiring the discrimination of odd-item different displays (one or
      more of the display's component elements differed) from same displays (all
      display components identical), pigeons were concurrently trained with sets of
      four discriminable display types. In each experiment, the consistent group was
      tested such that the same and different displays of four display types were
      consistently mapped onto their choice alternatives. The inconsistent group
      received a conflicting mapping of the same and different displays and the choice
      alternatives that differed across the four display types but were consistent
      within a display type. Experiment 1 tested experienced pigeons, and Experiment 2
      tested naive pigeons. In both experiments, the consistent group learned their
      discrimination faster and to a higher level of choice accuracy than did the
      inconsistent group, which performed poorly in general. Only in the consistent
      group was the discrimination transferred to novel stimuli, indicative of concept
      formation in that group. A third experiment documented that the different display
      classes were discriminable from one another. These results suggest that pigeons
      attempt to generate a single discriminative rule when learning this type of task,
      and that this general rule can cover a large variety of stimulus elements and
      organizations, consistent with previous evidence suggesting that pigeons may be
      capable of learning relatively unbounded relational same-different concepts.

PMID- 12507009
TI  - Brief presentations are sufficient for pigeons to discriminate arrays of same and
      different stimuli.
AB  - Four pigeons first learned to discriminate 16-item arrays of same from different
      pictorial stimuli. They were then tested with reduced exposure to the pictorial
      arrays, brought about by changes in the stimulus viewing requirement under fixed
      ratio (FR) and fixed-interval (FI) schedules. Increasing the FR requirement
      enhanced discriminative performance up to 10 pecks; increasing the FI requirement
      enhanced discriminative performance up to 5 s. Exposures to the stimulus arrays
      averaging only 2 s supported reliable discrimination. Pigeons thus discriminate
      same from different stimuli with considerable speed, suggesting that same
      different discrimination behavior is of substantial adaptive significance.

PMID- 12507010
TI  - A functional-analytic model of analogy: a relational frame analysis.
AB  - The aim of this study was to explore a behavior-analytic model of analogical
      reasoning, defined as the discrimination of formal similarity via equivalence
      equivalence responding. In Experiment 1, adult humans were trained and tested for
      the formation of four three-member equivalence relations: A1-B1-C1, A2-B2-C2, A3
      B3-C3, and A4-B4-C4. The B and C stimuli were three-letter nonsense syllables,
      and the A stimulus was a colored shape. Subjects were then successfully tested
      for equivalence-equivalence responding (e.g., matching B1/C1 to B2/C2 rather than
      B3/C4). These tasks were designed such that equivalence-equivalence responding
      might allow subjects to discriminate a physical similarity between the relations
      involved. Some participants (color subjects) received only equivalence
      equivalence tasks in which they might discriminate a color relation, whereas
      others (shape subjects) were given tasks in which they might discriminate a shape
      relation. A control group received both types of task. In a subsequent test for
      the discrimination of formal similarity, color subjects matched according to
      color, shape subjects matched according to shape, and the control group showed no
      consistent matching pattern. In Experiment 2, adult humans showed a
      transformation of the functions of a block-sorting task via this basic model of
      analogy. Empirical and conceptual issues related to these results are discussed.

PMID- 12507011
TI  - A new approach to the formation of equivalence classes in pigeons.
AB  - Four pigeons were given simultaneous discrimination training with visual patterns
      arbitrarily divided into two sets, with the stimuli in one set designated A1, B1,
      C1, and D1 and those in the other set designated A2, B2, C2, and D2. In
      sequentially introduced training phases, the pigeons were exposed to a series of
      reversals to establish AB and then CD equivalences. In subsequent testing
      sessions, a subset of stimuli from one set served as positive stimuli and those
      from the other set as negative stimuli on training trials, and transfer of the
      reinforced relation to other members of the sets was tested with nonreinforced
      probe trials. The pigeons were trained further on AC and BD equivalences and then
      were tested for the emergence of untrained AD and BC equivalences. Two of the 4
      pigeons exhibited the emergence of one of these untrained equivalences, evidence
      for the emergence of transitive relations. This finding suggests that the pigeons
      established three-member functional equivalence classes by incorporating
      separately trained multiple equivalence relations. Repeated reversal training and
      probe testing enabled us to explore the formation and expansion of functional
      equivalence classes in pigeons.

PMID- 12507012
TI  - The development of emergent differential sample behavior in pigeons.
AB  - Three experiments attempted to replicate Manabe, Kawashima, and Staddon's (1995)
      finding of emergent differential sample behavior in budgerigars that has been
      interpreted as evidence of functional equivalence class formation. In Experiments
      1 and 2, pigeons initially learned two-sample/ two-alternative matching to sample
      in which comparison presentation was contingent on pecking one sample on a
      differential-reinforcement-of-low-rate (DRL) schedule and the other on a fixed
      ratio (FR) schedule. Later, two new samples were added to the task. Comparison
      presentation on these trials occurred after the first sample peck following a
      predetermined interval (Experiment 1) or after completion of either the DRL or FR
      requirement, whichever occurred first (Experiment 2). Experiment 1 found no
      evidence for emergent spaced versus rapid responding to the new samples as they
      established conditional control over the familiar choices. By contrast,
      differential responding did emerge for some pigeons in Experiment 2, with
      responding to each new sample coinciding with the pattern explicitly conditioned
      to the original sample occasioning the same comparison choice. This emergent
      effect, however, disappeared for most pigeons with continued training. Experiment
      3 systematically replicated Experiment 2 using differential peck location as the
      sample behavior. Differential location pecking emerged to the new samples for
      most pigeons and remained intact throughout training. Our findings demonstrate a
      viable pigeon analogue to the budgerigar emergent calling paradigm and are
      discussed in terms of equivalence- and non-equivalence-based processes.

PMID- 12507013
TI  - Contextual control of stimulus generalization and stimulus equivalence in
      hierarchical categorization.
AB  - The purpose of this study was to determine whether hierarchical categorization
      would result from a combination of contextually controlled conditional
      discrimination training, stimulus generalization, and stimulus equivalence.
      First, differential selection responses to a specific stimulus feature were
      brought under contextual control. This contextual control was hierarchical in
      that stimuli at the top of the hierarchy all evoked one response, whereas those
      at the bottom each evoked different responses. The evocative functions of these
      stimuli generalized in predictable ways along a dimension of physical similarity.
      Then, these functions were indirectly acquired by a set of nonsense syllables
      that were related via transitivity relations to the originally trained stimuli.
      These nonsense syllables effectively served as names for the different stimulus
      classes within each level of the hierarchy.

PMID- 12507014
TI  - Sea lions and equivalence: expanding classes by exclusion.
AB  - Experiments have shown that human and nonhuman subjects are capable of performing
      new arbitrary stimulus-stimulus relations without error. When subjects that are
      experienced with matching-to-sample procedures are presented with a novel sample,
      a novel comparison, and a familiar comparison, most respond by correctly
      selecting the novel comparison in the presence of the new sample. This exclusion
      paradigm was expanded with two California sea lions that had previously formed
      two 10-member equivalence classes in a matching-to-sample procedure. Rather than
      being presented with a novel sample on a given trial, the sea lions were
      presented with a randomly selected familiar member of one class as the sample.
      One of the comparisons was a randomly selected familiar member of the alternative
      class, and the other was a novel stimulus. When required to choose which
      comparison matched the sample, the subjects reliably rejected the familiar
      comparison, and instead selected the unfamiliar one. Next, the sea lions were
      presented with transfer problems that could not be solved by exclusion; they
      immediately grouped the new stimuli into the appropriate classes. These findings
      show that exclusion procedures can rapidly generate new stimulus relations that
      can be used to expand stimulus classes.

PMID- 12507015
TI  - Stimulus control topographies and tests of symmetry in pigeons.
AB  - Pigeons were tested for symmetry after A-B training under conditions designed to
      avoid problems that may prevent its emergence, namely the change of stimulus
      location in testing relative to training and the lack of requisite discrimination
      training. In Experiment 1, samples appeared in two locations during baseline
      training to minimize the impact of stimulus location. Experiments 2 and 3
      included multiple-location training along with additional identity and symbolic
      matching training, respectively, to explicitly train all of the simultaneous and
      successive stimulus discriminations required for testing. Experiment 4 provided
      reinforcement for symmetrical matching relations with some stimulus sets (with
      multiple-location training) prior to symmetry testing with different sets. In all
      experiments, pigeons showed no evidence of symmetry despite the fact that
      baseline (A-B) matching transferred to novel locations. Additional tests for
      reflexivity (Experiment 2) yielded similar outcomes. These results indicate that
      the change in stimulus location is not the sole reason that pigeons do not show
      symmetry and increase the plausibility of arguments that symmetry and other
      indexes of stimulus equivalence may be beyond the capabilities of the pigeon.

PMID- 12507016
TI  - Chimpanzee responding during matching to sample: control by exclusion.
AB  - Three chimpanzees performed a computerized matching-to-sample task in which
      samples were photographs of items and comparison stimuli were geometric symbols
      called lexigrams. In Experiment 1, samples were either defined (i.e., they
      represented items that were associated already with a specific lexigram label by
      the chimpanzees) or undefined (i.e., they did not have an already learned
      association with a specific lexigram). On each trial, the foil (incorrect)
      comparison could be either a defined or an undefined lexigram. All 3 chimpanzees
      selected the correct comparison for undefined samples at a level significantly
      better than chance only when the foil comparison was defined. In Experiment 2,
      three comparisons were presented on each trial, and in Experiment 3, four
      comparisons were presented on each trial. For Experiments 2 and 3, the foil
      comparisons consisted of either defined or undefined comparisons or a mixture of
      both. For these two experiments, when the chimpanzees were presented with an
      undefined sample, they typically made selections of only undefined comparisons.
      These data indicate that the chimpanzees responded through use of exclusion. A
      final experiment, however, indicated that, despite the use of exclusion to
      complete trials with undefined samples correctly, the chimpanzees did not learn
      new associations between undefined samples and comparisons.

PMID- 12507017
TI  - On the role of covarying functions in stimulus class formation and transfer of
      function.
AB  - This experiment investigated whether directly trained covarying functions are
      necessary for stimulus class formation and transfer of function in humans.
      Initial class training was designed to establish two respondent-based stimulus
      classes by pairing two visual stimuli with shock and two other visual stimuli
      with no shock. Next, two operant discrimination functions were trained to one
      stimulus of each putative class. The no-shock group received the same training
      and testing in all phases, except no stimuli were ever paired with shock. The
      data indicated that skin conductance response conditioning did not occur for the
      shock groups or for the no-shock group. Tests showed transfer of the established
      discriminative functions, however, only for the shock groups, indicating the
      formation of two stimulus classes only for those participants who received
      respondent class training. The results suggest that transfer of function does not
      depend on first covarying the stimulus class functions.

PMID- 12507018
TI  - Naming and categorization in young children: vocal tact training.
AB  - In three experiments, 2- to 4-year-old children, following pretraining with
      everyday objects, were presented with arbitrary stimuli of differing shapes. In
      Experiment 1A, 9 subjects were trained one common tact response, "zag," to three
      of these and a second tact, "vek," to another three. In category match-to-sample
      Test 1, 4 subjects sorted accurately when required only to look at the sample
      before selecting from five comparisons. The remaining 5 subjects succeeded in
      Test 2, in which they were required to tact the sample before selecting
      comparisons. Experiment 1B showed, for 2 of these subjects, that tact training
      with 12 arbitrary stimuli established two six-member classes that were still
      intact 6 weeks later. In Experiment 2, 3 new subjects participated in a common
      tact training procedure that ensured that none of the exemplars from the same
      class were presented together prior to the test for three-member classes. Two
      subjects passed category Test 1 and the third passed Test 2. Tests showed
      subjects' listener behavior in response to hearing /zog/ and /vek/ to be in
      place. These experiments indicate that common naming is effective in establishing
      arbitrary stimulus classes and that category match-to-sample testing provides a
      robust measure of categorization.

PMID- 12507019
TI  - The competition-among-relations-in-nominals theory of conceptual combination:
      implications for stimulus class formation and class expansion.
AB  - One way in which new concepts are added to the conceptual system is through
      conceptual combination. The competition-among-relations-in-nominals (CARIN)
      theory (Gagne & Shoben, 1997) proposes that conceptual combination involves
      specifying a thematic relation (e.g., noun MADE OF modifier) to link the
      constituent concepts (e.g., chocolate and bee). This theory claims that relations
      have different strengths for various concepts that correspond to how often a
      modifier and relation have been paired in previous encounters with combined
      concepts and that this relational knowledge strongly affects the ease with which
      combined concepts can be formed. A mathematical model that incorporates key
      claims of the theory is presented, and empirical findings that are relevant to
      evaluating the CARIN theory are reviewed. The parallels between the CARIN theory
      and approaches to stimulus class formation are also discussed.

PMID- 12507020
TI  - Toward a unified theory of decision criterion learning in perceptual
      categorization.
AB  - Optimal decision criterion placement maximizes expected reward and requires
      sensitivity to the category base rates (prior probabilities) and payoffs (costs
      and benefits of incorrect and correct responding). When base rates are unequal,
      human decision criterion is nearly optimal, but when payoffs are unequal,
      suboptimal decision criterion placement is observed, even when the optimal
      decision criterion is identical in both cases. A series of studies are reviewed
      that examine the generality of this finding, and a unified theory of decision
      criterion learning is described (Maddox & Dodd, 2001). The theory assumes that
      two critical mechanisms operate in decision criterion learning. One mechanism
      involves competition between reward and accuracy maximization: The observer
      attempts to maximize reward, as instructed, but also places some importance on
      accuracy maximization. The second mechanism involves a flat-maxima hypothesis
      that assumes that the observer's estimate of the reward-maximizing decision
      criterion is determined from the steepness of the objective reward function that
      relates expected reward to decision criterion placement. Experiments used to
      develop and test the theory require each observer to complete a large number of
      trials and to participate in all conditions of the experiment. This provides
      maximal control over the reinforcement history of the observer and allows a focus
      on individual behavioral profiles. The theory is applied to decision criterion
      learning problems that examine category discriminability, payoff matrix
      multiplication and addition effects, the optimal classifier's independence
      assumption, and different types of trial-by-trial feedback. In every case the
      theory provides a good account of the data, and, most important, provides useful
      insights into the psychological processes involved in decision criterion
      learning.

PMID- 12507021
TI  - Modern imaging of the musculoskeletal system: is there still a role for
      radiography?

PMID- 12507022
TI  - The use of sildenafil in patients with erectile dysfunction in relation to
      diabetes mellitus--a study of 1,511 patients.
AB  - Erectile dysfunction (ED) seriously impairs the quality of life. Patients with
      diabetes mellitus (DM) are prone to ED due to various factors, including
      vasculopathy, neuropathy and sex hormone abnormalities. This is a retrospective
      study involving 1,511 patients taking sildenafil. Patients with DM have
      significantly more comorbidities like hypertension and ischaemic heart disease.
      They are also more likely to be on medications which may affect erectile
      function, including various antihypertensive drugs. 77.9% of patients with DM
      reported success with sildenafil, as compared to 86.5% of patients without DM. A
      significant number of patients with DM require a higher dose of sildenafil as
      compared to those without DM.

PMID- 12507023
TI  - The effects of treating lower urinary tract symptoms on health-related quality of
      life: a short-term outcome.
AB  - OBJECTIVES: This study examined the effects of treatment of lower urinary tract
      symptoms (LUTS) on the health-related quality of life (physical/functional,
      mental, social and global aspect), pain and prostatic symptoms. PATIENTS AND
      METHODS: The study consisted of 123 LUTS patients on medical treatment (alpha
      blockers) and 52 who underwent surgical treatment (TURP). The patients were
      assessed one week before and three months after medical and surgical treatment by
      using the Health-Related Quality of Life (HRQOL-20), the Visual Analogue Scale of
      Pain (VAS), the Present Pain Intensity (PPI) and the International Prostate
      Symptom Score (I-PSS) inventories and questionnaires. RESULTS: Prior to
      treatment, the surgically treated patients were found to suffer more pain, severe
      prostatic symptoms, bothersomeness and deterioration in health-related quality of
      life than the medically treated patients. Postoperatively, the surgical group
      showed a significant reduction and improvement in all aspects of pain, prostatic
      symptoms, bothersomeness and overall health-related quality of life, as compared
      with the medication group. The mean ages of the surgical and medical treated
      groups were 69.56 years (SD=7.94 years) and 64.62 years (SD=7.94 years)
      respectively. CONCLUSIONS: The result showed that operative procedure had
      significantly improved the overall health-related quality of life of LUTS
      patients compared to those on medical treatment.

PMID- 12507024
TI  - An assessment of the role of exhaled carbon monoxide in acute asthmatic
      exacerbations in hospitalised patients.
AB  - Exhaled carbon monoxide is a useful marker of airway inflammation in untreated
      asthma. Whether exhaled CO is clinically useful in steroid treated patients in a
      hospital setting is uncertain. We therefore studied exhaled CO as a marker of
      asthma severity in clinical practice. Non-smoking "acute" asthmatics
      (hospitalised; n=33), "stable" asthmatics (n=35), and healthy controls (n=22)
      were recruited. Exhaled CO, peak expiratory flow (PEF) and FEV1 were measured
      daily (hospitalised cases) or once only (stable outpatients). Inpatients were
      managed without knowledge of the results. Exhaled CO levels in acute asthmatics
      (initial levels), stable asthmatics and controls were similar (median=2.0 ppm,
      h=5.05, p=0.08). In acute asthmatics, initial exhaled CO did not correlate with
      duration of hospitalisation, doses of intravenous corticosteroids, doses of
      nebulised salbutamol, PEF (% predicted) or FEV1 (% predicted). In stable
      asthmatics, exhaled CO did not correlate with corticosteroid dosage, PEF (%
      predicted) or FEV1 (% predicted). In the setting of acute hospitalised asthma
      patients, exhaled CO may not add any further to clinical management. This may in
      part be due to prior treatment with corticosteroids.

PMID- 12507025
TI  - Laparoscopic hysterectomy versus abdominal hysterectomy: a controlled study of
      clinical and functional outcomes.
AB  - OBJECTIVE: To compare the clinical and functional outcomes of patients undergoing
      laparoscopic versus open hysterectomy for benign gynaecological pathology.
      SETTING: Gynaecological unit in a university hospital. METHODOLOGY: Forty
      consecutive cases of laparoscopic hysterectomy performed by the first author
      between June 1994 and December 1998 were reviewed. Their post-operative clinical
      and functional outcomes were compared with that of 40 patients with similar
      uterine size who had abdominal hysterectomy through a Pfannenstiel incision
      performed by consultant gynaecologists over the same time period. FINDINGS:
      Thirty-seven (92.5%) of the 40 patients had successful completion of laparoscopic
      hysterectomy. Of the patients who had successful laparoscopic hysterectomy, the
      duration of surgery was longer (mean duration: 159 vs 98 minutes), but they had a
      lower risk of complications (8.1% vs 20%), reduced analgesic requirement (mean
      pethidine dose: 93 vs 199 mg), and stayed for a shorter time in hospital (mean
      post-operation stay: 3.1 vs 4.9 days) when compared with patients who had
      abdominal hysterectomy. They were also able to return to full domestic function
      and sexual activity earlier. More patients in the laparoscopic hysterectomy group
      were happy with the appearance with the surgical scar, and the overall
      satisfaction with the surgery was also more positive than those who had abdominal
      hysterectomy. CONCLUSION: Laparoscopic hysterectomy is associated with improved
      clinical and functional outcomes when compared with open hysterectomy.

PMID- 12507026
TI  - Validation of 13C-urea breathtest for the diagnosis of Helicobacter pylori
      infection in the Singapore population.
AB  - INTRODUCTION: Several tests are available for determining the presence of
      Helicobacter pylori (H. pylori) infection. These may be invasive or non-invasive.
      The carbon urea breath test (C-UBT) is generally considered to be a simple, non
      invasive and accurate test for the detection of H. pylori infection both before
      and after treatment. Commercially available 13C-UBT kits are generally validated
      in their country of manufacture and the stated accuracy of their tests may not be
      applicable to our local population. AIM: The aim of our study was to determine
      the accuracy of a commercial 13C-urea breath test kit, Hp-Plus (Utandningstester
      i Sverige AB, Sweden), in the Singapore population. PATIENTS AND METHODS: One
      hundred patients for oesophago-gastro-duodenoscopy (OGD) were recruited into this
      prospective study. Gastric biopsies were obtained for the biopsy urease test and
      histological examination. Blood samples were obtained for H. pylori serology.
      Breath samples were then obtained at baseline and after consumption of 100 mg of
      labelled 13C-urea. The presence of H. pylori infection was defined by a positive
      result on any two of the three tests (biopsy urease test, histology, serology)
      performed for the detection of H. pylori. Using this "gold standard", the
      sensitivity, specificity, and positive and negative predictive values of the 13C
      UBT were calculated. RESULTS: In the Singapore population, the 13C-UBT (Hp plus)
      has a sensitivity and specificity of 94.2% and 100% respectively for the
      detection of H. pylori infection. The positive predictive value and negative
      predictive value of the 13C-UBT is 100% and 88.6% respectively. CONCLUSION: The
      13C-UBT is a simple, safe, and accurate non-invasive test for the detection of H.
      pylori infection, making it a valuable tool in local clinical practice.

PMID- 12507027
TI  - Practical issues relating to intranasal steroid therapy.

PMID- 12507028
TI  - The pattern of utilisation and accuracy of a commercial nucleic acid
      amplification test for the rapid diagnosis of Mycobacterium tuberculosis in
      routine clinical practice.
AB  - BACKGROUND: Several nucleic acid amplification (NAA) tests are available for the
      rapid detection of Mycobacterium tuberculosis (MTB) in clinical specimens. AIMS:
      To identify the pattern of utilisation and accuracy of the AMPLICOR test in
      routine clinical practice in an acute care setting. DESIGN: A retrospective
      descriptive study. METHOD: We studied 159 consecutive specimens in which the
      AMPLICOR (Roche; Branchburg, NJ) test was requested by attending doctors. The
      sensitivities and specificities of the AMPLICOR for detection of active
      tuberculosis (TB) were calculated in relation to types of specimens, smear and
      culture results. RESULTS: The number of requests more than doubled from 1999 to
      2000. Thirty-eight percent of the specimens were not from the respiratory tract.
      The majority of the specimens had requests for one or more additional test (mean
      1.8). The rate of active TB was 18%. The sensitivities of the AMPLICOR on per
      specimen, per patient, per smear negative specimen and per smear negative patient
      basis were found to be 81%, 80%, 66.7% and 71.4% respectively. The specificities
      for these groups accordingly were 99%, 98.6%, 99% and 98.6% respectively. The
      sensitivity and specificity for respiratory specimens were 97.5% and 98.5%, while
      for non-respiratory specimens, they were 60% and 100%. In smear negative
      specimens, the sensitivity and specificity for respiratory specimens were 60% and
      98.5%, while for non-respiratory specimens, they were 75% and 100%. The AMPLICOR
      assay was negative in all 21 specimens of pleural or spinal fluid. CONCLUSIONS:
      There is a growing demand for NAA in the rapid diagnosis of TB with a high
      proportion of non-respiratory specimens. The number of additional diagnostic
      tests performed on each specimen should be limited. In routine clinical practice,
      the AMPLICOR assay is a useful confirmatory test for active pulmonary TB. The
      utility of the AMPLICOR assay for MTB detection in exudative fluid specimens
      needs further evaluation.

PMID- 12507029
TI  - Immune haemolysis after renal transplantation secondary to ABO minor-mismatch
      between donor and recipient.
AB  - Immune haemolysis following renal transplantation has been reported and known
      causes include infection, medication and metabolic disturbances (1,2). Autoimmune
      haemolysis after renal transplantation secondary to ABO minor mismatch is an
      uncommon but important cause that should be considered in the differential
      diagnosis of post-transplantation haemolysis. A case of haemolytic anaemia caused
      by graft versus host antibody formation is presented. We suggest that direct
      Coomb's test should be done as a routine in all cases of ABO mismatch renal
      transplantation and red cells compatible with both donor and recipient or group
      "O" packed cells should be transfused if transfusion is indicated.

PMID- 12507030
TI  - A case of broken heart from blunt trauma.
AB  - A young man with blunt chest trauma presented acutely in shock as a result of
      cardiac rupture causing acute bloody tamponade. We discuss the clinical
      presentation, the importance of rapid and accurate diagnosis and management of
      such cases.

PMID- 12507031
TI  - Blood-volume: a commentary.
AB  - Under physiological conditions and on average, the total volume of blood in the
      circulation is constant. The total blood volume (BV) and the separate volumes of
      plasma and erythrocytes vary according to climatic conditions, in pregnancy and
      in the presence of disease. Such changes can have clinical significance although
      they are rarely revealed in common clinical practice because of a lack of
      availability of accurate, cheap and simple techniques for the measurement of BV.
      Diminution of BV may occur under intensive-care regimes and is life-threatening;
      acute exposure to a hot climate leads to an expansion of plasma volume and a
      corresponding fall in the circulating haemoglobin level. The same changes occur
      in normal pregnancy and are, perhaps, exaggerated in the tropics. Failure of
      expansion of PV in pregnancy has adverse effects on the foetus. New
      investigations in Singapore of BV in health, disease and pregnancy seem to be
      desirable now that people, including pregnant women, move frequently between a
      hot climate and a cold environment provided by air-conditioning.

PMID- 12507032
TI  - Article: Clinics in diagnostic imaging (66).

PMID- 12507033
TI  - Clinics in diagnostic imaging (76). Left extradural-intradural lumbar
      neurofibroma.
AB  - A 62-year-old woman presented with weight loss, anoexia and back pain. She was
      found to have a palpable left abdominal mass. Radiographs, CT and MR imaging
      revealed a large left 3rd lumbar neurogenic tumour with both intra- and
      extradural components. A neurofibroma was excised and the diagnosis was confirmed
      histopathologically. The patient has no recurrence at six years follow-up. The
      pathological classifications, clinical and imaging features of neurogenic tumours
      are discussed. With the knowledge of characteristic imaging features, these
      tumours can be differentiated from other types of intradural-extramedullary
      tumours.

PMID- 12507034
TI  - Antibody responses in sheep vaccinated against Staphylococcus aureus mastitis: a
      comparison of two experimental vaccines containing different adjuvants.
AB  - A double-blind, placebo-controlled study was conducted to compare two vaccines
      using different adjuvants with regard to their ability to stimulate antibody
      production against the alpha- and beta-toxins and the exopolysaccharide of
      Staphylococcus aureus. The vaccines contained identical antigens, consisting of
      inactivated whole bacteria of two strains of S. aureus in addition to alpha- and
      beta-toxoid. One vaccine contained mineral oil, while the other used a water
      soluble acrylic acid polymer resin (Carbopol) as adjuvant. Saline served as the
      placebo. One hundred and forty ewes were vaccinated twice before lambing, by
      subcutaneous injection with vaccine or placebo in the region of the supramammary
      lymph node, and were observed and sampled over a period of 6 months. The vaccine
      containing mineral oil as adjuvant induced significantly greater immune responses
      to the alpha- and beta-toxins than did the vaccine containing Carbopol. The
      latter vaccine induced higher levels of antibodies to exopolysaccharide. The
      degree of local adverse reactions did not differ between the two groups. The
      results indicate differences between the oil-adjuvanted and Carbopol-adjuvanted
      vaccines with regard to their ability to stimulate antibody production against S.
      aureus protein antigens in sheep.

PMID- 12507035
TI  - Serological evidence for Borrelia burgdorferi infection associated with clinical
      signs in dairy cattle in Slovakia.
AB  - In the course of epizootological research on Lyme borreliosis in domestic and
      farm animals, the serological evidence for the occurrence of this zoonosis in
      cattle was screened. An ELISA showed that 25.2% of cattle from seven geographical
      areas in Slovakia were positive for anti-Borrelia IgG antibodies. In particular
      localities, the seroprevalence ranged from 0.6% to 34.3%. Of 33 cases with
      clinical signs, 20 ELISA-positive samples were also confirmed in Western blots.
      The most frequent clinical signs were lameness and swollen joints, but most of
      the cases were asymptomatic. The occurrence of Borrelia burgdorferi antibodies
      and suspected clinical signs in cattle of Slovak regions indicates that
      veterinarians should pay attention to this disease in their clinical practice and
      include it within the differential diagnosis.

PMID- 12507036
TI  - A retrospective study of hyposensitization in canine atopy based on a polyclonal
      ELISA test.
AB  - Compliance with the treatment protocol and the most significant reasons
      encountered in general practice for the discontinuation of treatment in
      hyposensitized dogs are examined. The data are based on (1) a review of order
      forms for the hyposenzitization mixture and information sheets for an ELISA test
      and (2) telephone interviews with dog owners. Most of the owners (81%) gave their
      dogs allergen injections at home. Non-compliance was defined as discontinuation
      of treatment in the induction period; 33.9% of the owners became non-compliant. A
      large proportion of non-compliant owners (51.2%) claimed to be unaware of the
      length of the induction period. Furthermore, 70.2% of the owners were not aware
      that treatment would most likely need to be lifelong if it was to remain
      effective. Although 67.5% of the owners perceived that their dogs had beneficial
      effects from hyposensitization, only 36.3% of the dogs were receiving maintenance
      injections at the time of the telephone interview, considerably reducing the long
      term benefit from treatment. Canine atopy is a chronic disease characterized by
      remission and relapses. Since no control group was available in this study, the
      beneficial outcome of treatment reported by the owners could be partly due to the
      natural course of the disease. Nevertheless, the results indicated that the long
      term effect of hyposensitization in canine atopy will be reduced by premature
      discontinuation of treatment in the maintenance period. The discontinuation of
      treatment could be a reflection of the treatment becoming less effective, owing
      to the development of new hypersensitivities or to a reduction in the placebo
      effect that may occur in 'new' treatments. However, poor client education and
      follow-up seem to be important reasons for both noncompliance and discontinuation
      of the treatment in the maintenance period.

PMID- 12507037
TI  - Haemorheological variables in a rat model of hypertriglyceridaemic obesity and
      diabetes.
AB  - Obesity is a heterogeneous condition of variable aetiology, generally associated
      with pathologies such as arterial hypertension, hyperlipidaemia, diabetes and
      cardiac disease. These conditions, either themselves or because of the various
      treatments used, may further modify blood rheology in an arbitrary manner.
      Therefore, analyses of changes in the blood rheology induced by obesity in humans
      have had differing and controversial results. In our laboratory, a model of
      hypertriglyceridaemic obesity is provided by an inbred rat strain; the beta
      genotype from the IIMb/Fm strain, presenting a syndrome of moderate obesity with
      apparent peripubertal onset, associated with hypertriglyceridaemia and glucose
      intolerance that turns into diabetes. The alpha genotype, originated from the
      same IIM/Fm stock, represents the control. The present study describes a
      comparative analysis of the variables determining the rheological behaviour of
      the blood in obese and control strains. Our results, agreeing with some other
      studies performed in humans, confirmed the haemorheological changes associated
      with obesity, and the fact that these changes became more evident in the presence
      of pathologies such as diabetes. It appears that triglyceridaemia.
      cholesterolaemia and hyperglycaemia may influence the rheological behaviour of
      the cell membrane and this damage may provoke a decrease in erythrocyte
      deformability and, consequently, hyperviscosity of the blood.

PMID- 12507038
TI  - Muscarinic receptors in equine airways.
AB  - The distribution of muscarinic receptors in equine airways was investigated using
      autoradiography. Frozen sections of tissue from six different levels in the
      bronchial tree, from the trachea to the distal bronchioles, were incubated in
      vitro with 1.5 nmol/L of the muscarinic receptor antagonist 1-[N-methyl
      3H]scopolamine methyl chloride (3H-NMS). In addition, the subtype pattern of
      muscarinic receptors was investigated in equine tracheal smooth muscle using
      radioligand binding with methoctramine, tripinamidc, 4-DAMP-methiodide and
      pirenzipine as competitors against the binding of 1.3 nmol/L 3H-NMS. The
      autoradiograms showed specific labelling indicating a high density of muscarinic
      receptors in smooth-muscle tissue in all levels of the airway tree investigated.
      Besides muscle tissue, subepithelial glands were the only structures specifically
      labelled. The dominating subtypes in tracheal smooth muscle investigated with
      radioligand binding studies were found to be M2 and M4, as both methoctramine
      (pKd = 8.5) and tripinamide (pKd = 8.6 and 6.7 for two different sites) showed
      high affinity. The density of the M3-muscarinic receptor subtype was low, but
      this subtype could be detected with statistical significance when methoctramine
      was used as the competitor against 3H-NMS binding.

PMID- 12507039
TI  - Dose-dependent response to an intratesticular injection of calcium chloride for
      induction of chemosterilization in adult albino rats.
AB  - This study concerned the minimum and optimum effective doses of calcium chloride
      needed for induction of chemosterilization in male albino rats, 30 days after a
      single intratesticular injection of calcium chloride (CaCl2.2H2O) solution at
      2.5, 5, 10 or 20 mg per 100 g body weight per testis. There was a significant
      diminution in the relative wet weight of the sex organs (p<0.01), epididymal
      sperm count (p<0.001), plasma concentration of testosterone (p<0.01), testicular
      activities of delta5,3beta-hydroxy steroid dehydrogenase (delta5,3beta-HSD),
      17beta-hydroxy steroid dehydrogenase (17beta-HSD) (p<0.01), glutathione S
      transferase (GST) (p<0.01), superoxide dismutase (SOD) (p<0.01), and peroxidase
      (p<0.01), significant elevations in testicular content of malondialdehyde (MDA)
      and conjugated dienes (p<0.01), along with derangement of seminiferous tubular
      architecture and degeneration of the Leydig cells in the testis and elevations in
      the concentrations in the plasma of LH and FSH (p<0.01), commencing at a dose of
      5 mg, with the greatest effects at a dose of 20 mg. No significant alterations in
      these factors occurred at the dose of 2.5 mg in comparison to the control that
      received only the vehicle. There was no significant alteration in the plasma
      concentrations of prolactin (p>0.05), corticosterone (p>0.05) or fasting blood
      glucose or in the rectal temperature (p>0.05) at any of the doses relative to the
      control group, suggesting that this chemosterilizing procedure did not exert any
      chronic stress on the experimental animals. From these observations, it may be
      suggested that 5 mg should be considered as the minimum dose, and 10 mg or 20 mg
      as the optimum dose, whereas 2.5 mg was ineffective for induction of
      chemosterilization. There would seem to be little point in using more than 20 mg
      of calcium chloride for this purpose. Intratesticular injection of calcium
      chloride at an effective dose may be considered as an alternative to surgical
      castration.

PMID- 12507040
TI  - On the impact of different number representations in the number bisection task.
AB  - The number bisection task--in which the numerical middle of two other numbers has
      to be determined (e.g., 6 is the numerical middle of 4 and 8)--has recently been
      used in neuropsychological case studies in addition to the number comparison task
      to assess quantitative capabilities in number processing. While factors
      determining difficulty in normal participants have often been systematically
      investigated in the number comparison task, this has not yet been done in the
      number bisection task. Based on a pilot study by van Herten (1999), we extracted
      four factors that we hypothesized to modulate difficulty in a verification
      version of the number bisection task in normal participants: Multiplicativity
      (whether or not the three numbers are part of a multiplication table), range
      (distance between the smallest and the largest number) for bisectable number
      triplets as well as distance of the middle number to the numerical middle, and
      bisection possibility for non-bisectable triplets. In the current study, we
      obtained large effects for all four factors on RT and accuracy data and some
      interesting interactions in normal participants. In a regression analysis, we
      additionally observed inhibitory effects of decade crossing and of ten inclusion
      (whether or not one of the three numbers was a decade number). We discuss the
      impact of these results for the use of the number bisection task as an assessment
      tool in neuropsychology. Finally, we examine the consequences of these results
      for models of number processing.

PMID- 12507041
TI  - Pure topographical disorientation--the anatomical basis of landmark agnosia.
AB  - We used MRI studies of four patients to investigate the lesions responsible for
      landmark agnosia. A detailed investigation of the relationship between the
      symptoms and the lesions suggests that the right posterior part of the
      parahippocampal gyrus is critical for the acquisition of novel information about
      buildings and landscapes, and that the same region plus the anterior half of the
      lingual gyrus and the adjacent fusiform gyrus play an important role in the
      identification of familiar buildings and landscapes. Furthermore, the lesion
      responsible for prosopagnosia, which frequently occurs with landmark agnosia,
      seems to involve the posterior half of the lingual and fusiform gyri. This
      suggests that the lesions responsible for landmark agnosia and prosopagnosia are
      close to each other, but distinct.

PMID- 12507042
TI  - Seeing happy emotion in fearful and angry faces: qualitative analysis of facial
      expression recognition in a bilateral amygdala-damaged patient.
AB  - Neuropsychological studies reported that bilateral amygdala-damaged patients had
      impaired recognition of facial expressions of fear. However, the specificity of
      this impairment remains unclear. To address this issue, we carried out two
      experiments concerning the recognition of facial expression in a patient with
      bilateral amygdala damage (HY). In Experiment 1, subjects matched the emotion of
      facial expressions with appropriate verbal labels, using standardized photographs
      of facial expressions illustrating six basic emotions. The performance of HY was
      compared with age-matched normal controls (n = 13) and brain-damaged controls (n
      = 9). HY was less able to recognize facial expressions showing fear than normal
      controls. In addition, the error pattern exhibited by HY for facial expressions
      of fear and anger were distinct from those exhibited by both control groups, and
      suggested that HY confused these emotions with happiness. In Experiment 2,
      subjects were presented with morphed facial expressions that blended happiness
      and fear, happiness and anger, or happiness and sadness. Subjects were requested
      to categorize these expressions by two-way forced-choice selection. The
      performance of HY was compared with age-matched normal controls (n = 8). HY
      categorized the morphed fearful and angry expressions blended with some happy
      content as happy facial expressions more frequently than normal controls. These
      findings support the idea that amygdala-damaged patients have impaired processing
      of facial expressions relating to certain negative emotions, particularly fear
      and anger. More specifically, amygdala-damaged patients seem to give positively
      biased evaluations for these negative facial expressions.

PMID- 12507043
TI  - Persistent cognitive deficits associated with lithium intoxication: a
      neuropsychological case description.
AB  - We present the case of a 51-year-old patient with an acute lithium intoxication
      associated with several cognitive deficits. During the acute phase of
      intoxication the patient displayed general psychomotor slowing, dysarthric
      speech, mood changes, and incoherent discourse. Neuropsychological assessment
      revealed ideomotor apraxia, profound deficits of visuospatial processing, an
      impairment of memory and of frontal-executive functions. Other cognitive
      abilities, such as orientation, spontaneous speech, comprehension, naming,
      reading, writing, and working memory remained intact. An electroencephalogram
      revealed diffuse slowing with rhythmic trains, whereas MRI showed no cerebral
      abnormality. Follow-up examinations at 4 and 14 weeks with lithium levels in the
      normal range showed substantial recovery of memory abilities and executive
      functions, whereas praxis and visuoperceptual functions remained impaired,
      despite the fact that lithium was immediately withdrawn after the intoxication
      became manifest. We conclude that lithium intoxication may be associated with
      variable behavioural and cognitive impairments, some of them potentially
      persistent. Different from other case studies our findings suggest that lithium
      intoxication may cause a combined, multifocal functional impairment of
      subcortical and cortical neural mechanisms in both hemispheres.

PMID- 12507044
TI  - Motor sequencing in Parkinson's disease: relationship to executive function and
      motor rigidity.
AB  - Parkinson's disease (PD) is a movement disorder that also affects central
      cognitive processing; however, the extent to which high-order cognitive processes
      disrupted by PD affect complex motor function is incompletely explicated. The
      present analysis provides an examination of the relative contributions of simple
      motor versus complex cognitive functions involving sequencing, problem solving,
      and overall cognitive status to complex motor movements involving sequencing and
      temporal ordering in PD. Motor sequencing performance was videotaped for
      quantitative scoring. Compared with an age-matched control group, the PD group
      was impaired on motor agility and motor sequencing tasks in addition to cognitive
      sequencing and set shifting tasks. Neither current cognitive functioning, age,
      disease duration, nor overall intellectual abilities accounted for the
      relationships between motor sequencing and cognitive sequencing abilities in PD.
      By contrast, both sequencing and nonsequencing executive functions predicted
      motor sequencing performance as well as or better than motor rigidity or overall
      cognitive status. These relationships were strongest for the most challenging
      motor sequencing task, fist-edge-palm, and did not apply to the least challenging
      task, which required simple alternations of hand movements. Unlike PD, controls
      showed correlations between motor sequencing tests and executive functioning only
      tapping nonsequencing abilities. Thus, despite the predominant motor feature of
      PD, executive functions, as assessed by sequencing and set formation, predicted
      motor sequencing performance as well as or better than simple motor performance.
      The results further suggest that the more complex the motor sequencing task, the
      more susceptible it is to influence from generalized cognitive sequencing
      ability.

PMID- 12507045
TI  - Far bias on the radial line bisection task: measuring perceptual-attentional and
      motor-intentional bias in normal subjects.
AB  - Normal subjects usually err distally when bisecting radial lines below eye level
      in midsagittal space (far bias). To learn if a radial line bisection bias may be
      characterized as primarily perceptual-attentional or primarily motor-intentional,
      we had subjects bisect lines while watching their hand and the line under two
      video monitoring conditions. In the DIRECT condition, proximal (near) and distal
      (far) on the video monitor corresponded with the workspace where subjects
      bisected lines. In the INDIRECT condition, we reversed proximal and distal as
      they appeared on the monitor. Thus, in the indirect condition, distal hand
      movement appeared proximal, and vice versa. In the DIRECT condition, subjects
      erred toward far space (mean 2.075 mm). In the INDIRECT condition, however,
      subjects erred proximally (mean 1.59 mm, near bias). Distal-proximal reversal of
      errors over the group of subjects is consistent with a primarily perceptual
      attentional bias. In lower body space, normal visual-perceptual-attentional
      systems may be more biased toward far space than are kinesthetic-motor systems.

PMID- 12507046
TI  - Academic achievement and learning abilities in left-handers: guilt or gift?
AB  - The main purpose of this cross-sectional study was to compare the acceptance rate
      (AR) of left-handers (LHs) with that of right-handers (RHs) in the college
      entrance examination (CEE) for the national universities in Iran. During 5
      successive years, fifty thousand participants in this exam were randomly sampled.
      We evaluated the relationships between AR and hand preference, sex, college
      admission (CA), entrance exam score (EES) and study areas: Mathematics, Natural
      Sciences, Humanities and Art. The acceptance rate of the LHs over the entire
      study period was significantly higher than that of the RHs (27.3% versus 24.3%, p
      < 0.0001). The mean score attained on examination by LHs was significantly higher
      than that of RHs in all study areas (p < 0.002). The acceptance rate of LHs in
      all study areas was higher but the difference reached statistical significance in
      the Art area only (p < 0.01). It is concluded that left-handers may be regarded
      as a heterogeneous large group consisting of different subgroups. Those who are
      able to compete for the college entrance examination score are even more
      successful than right-handers in terms of average EES and the rate of CA.

PMID- 12507047
TI  - Effect of background motion on line bisection performance in normal subjects.
AB  - Previous studies have demonstrated that optokinetic stimulation (OKS) influences
      line bisection (LB) performance in normal subjects and patients with hemispatial
      neglect. Since subjects were required to attend to stationary targets on a moving
      background, prior experimental designs might have induced an illusion of target
      motion or induced motion (IM) in a direction opposite the background. The current
      study tested whether the IM affects LB performance in normal subjects and how the
      speed of targets also influences LB. Thirty-two right-handed normal volunteers
      (aged 28.0 +/- 5.3 years) were asked to bisect stationary lines with a background
      of horizontal OKS. These stimuli were generated by computer displayed on a large
      screen via a beam projector. The OKS was varied according to direction (leftward
      or rightward) and speed (9.4 degrees/sec or 56.1 degrees/sec), producing 4
      different experimental conditions. Mean bisection errors in all conditions were
      compared with a control condition with no background OKS. For each condition,
      subjects rated the degree of IM on a 5 point scale. With fast rate OKS, subjects
      reported minimal IM and LB errors were in the same direction as background
      motion, a finding that replicates previous studies. Conversely, the slow OKS rate
      caused subjects to report IM and resulted in deviation of the bisection mark in a
      direction opposite the background OKS. While this discrepancy between the slow
      and fast OKS conditions might be related to motion illusion, we did not find a
      direct correlation between the degree of IM and bisection errors and thus reasons
      for these results remain unexplained.

PMID- 12507048
TI  - Impaired processing of affective prosody in Korsakoff's syndrome.
AB  - In order to further characterize reported deficits in affect perception in
      alcoholic Korsakoff patients, selected prosody subtests from the Tubingen Affect
      Battery were administered to seven Korsakoff patients and seven normal control
      participants. Results indicated that both linguistic and affective prosody
      discrimination were intact in Korsakoff patients. As well, affective prosody
      identification was unimpaired when the semantic content of the sentence was
      emotionally congruent with affective prosody. In contrast, affective prosody
      identification was significantly impaired when the semantic content was either
      neutral or incongruent with prosody. These results suggest that Korsakoff
      patients are impaired in interpreting the meaning of affective prosody in the
      absence of semantic cues as to the emotional content of sentences.

PMID- 12507049
TI  - Intermanual transfer in a simple motor task.
AB  - The present study examines the effects of a four-week training session in a
      pegboard task on uni- and bimanual performance. Of particular interest was
      whether practice transfer from the trained to the untrained hand takes place.
      Twenty-five consistently right-handed subjects were trained to perform the task
      with the dominant hand, or the subdominant hand, or with both hands. After this
      training, the learning effects for the trained and untrained hands were analysed.
      To summarise, we obtained the following findings: (1) After training, movement
      times were considerably reduced for all hands and for all training conditions
      (practice effects); (2) practice effects were found for the hand trained and also
      for the untrained hand; (3) there was not a great difference in the size of the
      practice effects for the right hand after left hand training or for the left hand
      after right hand training; (4) task difficulty had no clear influence on the
      practice effect; (5) and finally, we discovered that bimanual movements not only
      profit from bimanual training but also from unimanual training and conversely
      unimanual movements benefit from bimanual training. These findings are discussed
      in the context of different motor control models and in the light of recent brain
      imaging findings.

PMID- 12507050
TI  - Sunscreens can increase dermal penetration of 2,4-dichlorophenoxyacetic acid.
AB  - Agricultural workers are encouraged to wear sunscreen to reduce their risk of
      skin cancer. These workers are also exposed to herbicides during the course of
      their day. The skin is the major source of chemical exposure in agriculture. The
      purpose of this work is to determine the effect of sunscreen use on the
      transdermal absorption of a model herbicide, 2,4-dichlorophenoxyacetic acid.
      Hairless mouse skin was pretreated with one of nine commercially available
      sunscreens purchased at a local drug store. The herbicide 2,4
      dichlorophenoxyacetic acid was placed on top of the epidermis in an in vitro
      diffusion chamber for 24 hours. The total penetrating through the skin in 24
      hours ranged from 39.1 +/- 1.7% for the no sunscreen control to 81.0 +/- 2.8% for
      Neutrogena Oil Free Sunscreen. Of the nine sunscreens tested, six led to a
      significant enhancement of total 2,4-dichlorophenoxyacetic acid penetration as
      compared to the control (p < 0.01). Careful selection of sunscreen during
      pesticide application could reduce potential exposure.

PMID- 12507051
TI  - Characteristics of acute adult poisoning in Gaziantep, Turkey.
AB  - BACKGROUND: The objective of this prospective hospital-based study was to
      evaluate the rate and characteristics of acute human poisoning in our province
      (Gaziantep City, Turkey). METHODS: All cases of acute human poisonings admitted
      to the emergency department of the Gaziantep University Hospital, Gaziantep,
      Turkey, between January 2000 and December 2001, were included in the study. The
      rate and causes of mortality from poisoning as well as demographic data of the
      patients were investigated. RESULTS: There were 179 (0.7%) poisoning cases among
      25,605 patients who admitted to the emergency department. Of the poisoning cases,
      64.3% were female and 35.6% were male patients. The poisoning made a peak between
      the ages of 16 and 25. The majority of poisonings resulted from oral ingestion
      with deliberate intake accounting for 78.7% of the cases. Most of the suicide
      attempt cases were also females. Analgesics were the most common agents (42.4%)
      among the drugs incriminated in poisoning. Twenty-four patients (13.7%) were
      admitted to intensive care unit, of whom 42% were female and 58% were male
      patients. Drugs for suicide attempts were the main cause of poisoning in the
      patients who admitted to intensive care unit. Five patients (2.8% of all cases)
      died in the intensive care unit. CONCLUSIONS: These data provide important
      preliminary information on the pattern of symptomatic poisonings in this south
      east part of our country.

PMID- 12507052
TI  - Comparison of poison exposure data: NHIS and TESS data.
AB  - OBJECTIVE: To identify age-adjusted poisoning episode rates, and poison control
      center contacts due to poisonings in children under 6 years old based on 1997
      1999 National Health Interview Survey data; and compare findings with 1997-1999
      Toxic Exposure Surveillance System data. METHODS: Secondary analysis of National
      Health Interview Survey poisoning episode data for children 5 years and younger.
      Respondents were asked about poison exposures during the previous 3 months.
      RESULTS: Based on National Health Interview Survey population weighted data there
      were 196/10,000 poisonings to young children < 6 years. These exposures resulted
      primarily from harmful solid or liquid substances. A poison control center was
      called in 86% of exposures to children < 4 years, but only in 70% of the 4-5 year
      old exposures. The odds of a poison control center not being called were 3.2
      times greater for 4-5 year olds (compared to < or = 3 years) and 4.5 times
      greater for African-American (compared with White-Americans). Comparison of
      National Health Interview Survey data with data in the 1997-1999 Annual Reports
      of the Toxic Exposure Surveillance System revealed the number of estimated
      exposures in the National Health Interview Survey data were approximately half
      those reported in the Toxic Exposure Surveillance System data. In both datasets,
      children 1-2 years of age had the highest percent of poisoning exposures.
      CONCLUSIONS: Using multiple datasets to explore poisoning rates in young children
      provides a broader perspective. Differences in findings reflect divergent data
      collection methods and biases inherent in each database. Although the majority of
      National Health Interview Survey respondents reporting contacting a poison
      control center for a poisoning exposure, rates are lower in specific subgroups
      indicating a need for targeted educational efforts.

PMID- 12507053
TI  - Severe propanil [N-(3,4-dichlorophenyl) propanamide] pesticide self-poisoning.
AB  - BACKGROUND: Propanil pesticide poisoning can produce methemoglobinemia, tissue
      hypoxia, and depression of central nervous system and respiratory system. It has
      been recorded only rarely worldwide and most current poison texts consider
      propanil to be of low toxicity. However, propanil self-poisoning is a significant
      clinical problem in parts of Sri Lanka and an occasional cause of death. AIM OF
      STUDY: To report the clinical features and management of severe propanil
      poisoning. PATIENTS AND METHODS: We report a retrospective case series of
      patients who were treated in the intensive care unit of and/or died in
      Anuradhapura General Hospital between 1998 and early 2002. RESULTS: Sixteen
      patients were identified. Common manifestations of toxicity included confusion,
      reduced conscious level, cyanosis, and respiratory depression. Marked hemolysis
      was noted in several patients. Nine deaths occurred due to respiratory depression
      and cardiorespiratory arrest. Management was difficult given the lack of i.v.
      methylene blue, inability to measure methemoglobin levels, and paucity of
      intensive care unit beds. CONCLUSIONS: This series indicates that propanil
      poisoning can be a severe form of self-poisoning, particularly in resource-poor
      settings. We have now initiated the establishment of a prospective series of
      propanil poisoned patients to further describe its clinical features,
      responsiveness to therapy, and case fatality rate.

PMID- 12507054
TI  - Evaluating the utilization of a regional poison center by Latino communities.
AB  - BACKGROUND: Penetrance values estimate the utilization of poison centers
      services. For a variety of reasons, penetrance values may vary greatly among
      geographic areas of population. We examined the relationship between ethnicity
      and penetrance in our population. METHODS: We conducted a retrospective review of
      data from January 1, 2000 through December 31, 2000 from our poison center's
      database. Home calls to the center were evaluated by zip code, age, gender,
      substance, route of exposure, and outcome. These data were compared with U.S.
      Census 2000 geographic and community demographic data for San Diego by zip code.
      From this information, we identified zip code regions with substantial Latino
      populations (>50%), and substantial Caucasian populations (>70%). Study groups
      were limited to those zip codes with median household incomes of $20,000-$50,000.
      Aggregate total and pediatric penetrance values were calculated for each group
      and compared. RESULTS: Our study group consisted of 6 zip codes with significant
      numbers of Latino residents, and 11 zip codes with significant numbers of
      Caucasian residents. Aggregate call volume for the county was 6.5 calls per 1000
      population, while that for children less than age 5 was 43. Penetrance values for
      the study zip codes with large Latino populations were significantly lower with a
      mean value of 22.4 for children, and 5.0 for all ages. These values were
      statistically significant when compared to county data and that from the control
      zip codes with largely Caucasian residents (61 aggregate and 49.6 pediatric).
      CONCLUSION: Penetrance values were significantly lower in zip codes with large
      numbers of Latino residents. Reasons for this variation are being investigated.

PMID- 12507055
TI  - Topical treatments for hydrofluoric acid burns: a blind controlled experimental
      study.
AB  - BACKGROUND: Calcium gluconate gel, applied after initial rinsing with water, has
      a documented effect as first aid treatment for hydrofluoric acid burns.
      Hexafluorine is a novel liquid compound developed especially for emergency
      decontamination of hydrofluoric acid eye and skin exposures. However, scientific
      documentation of the effect of Hexafluorine is insufficient. This study was
      undertaken to compare Hexafluorine with water rinsing plus topical calcium and
      with water rinsing alone. METHODS: Thirty-five Sprague-Dawley rats were
      anesthetized and their backs shaved. Four filter papers 10 mm in diameter were
      soaked in 50% hydrofluoric acid and applied on the shaved area of each rat for 3
      minutes. Thirty seconds later, the acid-exposed skin areas were rinsed with 500
      mL Hexafluorine for 3 minutes (group H, n = 10), 500 mL water for 3 minutes
      (group W, n = 10) or 500 mL water for 3 minutes followed by a single application
      of 2.5% calcium gluconate gel (group Ca, n = 10), or received no treatment
      (controls, n = 5). The animals were closely observed for 5 days. Daily at 4 P.M.
      each of the four burns on every rat was rated on a modified Draize scale graded
      from 0 to 5 (0 = no visible injury, 1 = diffuse erythema, 2 = distinct erythema,
      3 = distinct erythema plus wounds or discolored spots, 4 = distinct erythema plus
      wounds or discolored areas covering >50% of the burn, 5 = a necrotic wound
      covering the whole burn). The mean of the four scores was then calculated for
      each animal and day. The rating procedure was performed by one laboratory
      assistant who was unaware of the treatment given. Kruskal-Wallis analysis was
      used to evaluate possible differences between treatment groups on each of the 5
      days. If the p-value obtained was <0.05, correction for multiple comparisons was
      made. RESULTS: The mean severity score in group H was significantly higher than
      that in group Ca on days 2 and 3. Moreover, Hexafluorine showed a consistent
      trend towards a worse outcome, both in comparison to water plus topical calcium
      and to water rinsing alone. CONCLUSION: Based on these observations it is
      concluded that water rinsing followed by topical calcium should remain the
      standard first aid treatment for skin exposure to hydrofluoric acid.

PMID- 12507056
TI  - Toxicologic myocardial sensitization.
AB  - Drug-induced polymorphic ventricular tachycardia (torsades de pointes) may lead
      to syncope or sudden cardiac death. One mechanism by which drugs and toxins may
      predispose to the development of this malignant dysrhythmia is through their
      ability to produce myocardial sensitization. The concept of myocardial
      sensitization actually represents a series of events involving altered cellular
      repolarization produced by blockade of myocardial potassium channels. Altered
      potassium ion flow raises the likelihood that an ectopic beat will occur via an
      early afterdepolarization and simultaneously alters the myocardial tissue to make
      it favorable for reentrant dysrhythmias, such as torsades de pointes, to
      propagate. Alternatively, calcium overload of the myocyte produces ectopy by
      causing delayed afterdepolarizations, which if the substrate for reentry is
      present, will result in ventricular tachycardia. This paper discusses the
      mechanisms underlying the production of both the altered myocardial substrate and
      the afterdepolarizations.

PMID- 12507057
TI  - A case of levetiracetam (Keppra) poisoning with clinical and toxicokinetic data.
AB  - BACKGROUND: Levetiracetam (Keppra) is a new anticonvulsant used to treat partial
      complex seizures that is also being investigated for its mood-stabilizing
      properties. Although its precise mechanism of action is unknown, levetiracetam
      does not appear to directly interact with the GABA system. We report the first
      intentional overdose with levetiracetam including clinical effects and serial
      serum concentrations. CASE REPORT: A 38-year-old woman reportedly ingested 60
      (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication
      for bipolar disorder. She had no other prescription medications available and no
      other medical history. She vomited 4 hours after ingestion and presented to the
      ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary
      to respiratory depression. Her only other significant clinical finding was
      diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine,
      phenytoin, and valproic acid levels were all negative as was a subsequent urine
      screen for drugs of abuse. Her levetiracetam serum concentration was 400
      microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours
      (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life
      was calculated to be 5.14 hours. She was extubated the next hospital day and
      recovered without sequelae. CONCLUSION: In overdose, levetiracetam is sedating
      and causes respiratory depression, however, recovery is rapid with supportive
      care. This is the first reported case of levetiracetam overdose; serial serum
      concentrations suggest first-order elimination even at concentrations 10-40 fold
      higher than therapeutic.

PMID- 12507058
TI  - An analysis of glyphosate data from the California Environmental Protection
      Agency Pesticide Illness Surveillance Program.
AB  - Glyphosate is among the pesticides most frequently reported to the California EPA
      Pesticide Illness Surveillance Program. We analyzed glyphosate-related calls to
      the Pesticide Illness Surveillance Program in order to assess the number of
      reports involving systemic symptoms and to better understand the nature and
      severity of reported cases. Data on glyphosate and other pesticides are available
      for the years 1982-1997 including: type of exposure (agricultural/other); target
      organ(s) affected (skin/eye/respiratory/systemic); exposure(s); an assessment of
      causal relationship (possible, probable, or definite); and limited medical text.
      Of 815 total glyphosate calls, most involved topical irritation of the eye (n =
      399), skin (n = 250), upper airway (n = 7), or combinations of these sites (n =
      32) without systemic symptoms. Of the 187 systemic cases, only 22 had symptoms
      recorded as probably or definitely related to glyphosate exposure alone. The
      reported symptoms were not severe, expected to be limited in duration, and
      frequently inconsistent with the route of exposure and/or previous experience
      with glyphosate. We conclude that call volume is not a reliable indicator of the
      actual incidence or severity of glyphosate-related incidents in California.

PMID- 12507059
TI  - Tools for clinical toxicology on the World Wide Web: review and scenario.
AB  - Clinical toxicologists are entrusted with the health and safety of humans and
      animals exposed to toxic substances. To do their jobs well they need a solid
      knowledge of toxicological principles, an ability to handle emergent situations,
      a "bedside" manner that results in a good rapport with patients, and the ability
      to access current and accurate information in order to properly care for the
      afflicted. An information armamentarium that is increasingly digital and Web
      based is becoming a necessity. This article reviews Web resources that can assist
      the toxicologist. A case scenario is presented to provide a practical perspective
      to the information tools outlined.

PMID- 12507060
TI  - Serum acetylcholinesterase and prognosis of acute organophosphate poisoning.
AB  - OBJECTIVE: The aim of this study is to investigate the prognostic value of serum
      acetylcholinesterase levels and their relationship with neurological syndromes
      (Type 1 syndrome, intermediate syndrome, and delayed polyneuropathy) in acute
      organophosphate poisoning. MATERIALS AND METHODS: Thirty-two consecutive patients
      with acute organophosphate poisoning admitted to the Ondokuz Mayis University
      Emergency Department from June 1999 to January 2001 were evaluated. Patients were
      assessed according to admission time, symptoms, and results of clinical exams and
      their serum acetylcholinesterase levels were determined on days 1, 2, 3, 7, and
      the last day. RESULTS: There was no significant difference between the first-day
      serum acetylcholinesterase of the patients with severe poisoning (n = 22, 68.75%)
      and of the patients with mild poisoning (n = 10, 31.25%; NS). There was no
      discernible difference between the serum acetylcholinesterase obtained on days 1
      and 3 after poisoning from the patients with intermediate syndrome (n = 5, 15.6%;
      means: 0.90 +/- 0.65 vs. 0.88 +/- 0.53, 19.35 vs. 18.92%; NS, sensitivity = 80%;
      specificity = 87.5%). There was a significant difference between the serum
      acetylcholinesterase obtained on days 1 and 3 from the patients with
      nonintermediate syndrome (n = 24, 75%; means: 1.05 +/- 0.24 vs. 1.68 +/- 0.29,
      22.58 vs. 36.12%; p < 0.001). There was no discernible significant difference in
      serum acetylcholinesterase between the patients with organophosphorus-induced
      delayed polyneuropathy (n = 7, 21.8%) and nonorganophosphorus-induced delayed
      polyneuropathy. In the patients who died (n = 5, 15.6%), serum
      acetylcholinesterase showed no discernible increase day 1-the last day (means:
      0.50 +/- 0.25 vs. 0.46 +/- 0.26, 10.75 vs. 9.89%; NS). There was a significant
      difference between the serum acetylcholinesterase levels obtained on days 1 and
      the last day from the patients who survived (n = 27, 84.3%; means: 1.14 +/- 0.25
      vs. 2.32 +/- 0.26, 24.51 vs. 49.89%; p < 0.001). CONCLUSION: In the acute phase
      of organophosphate poisoning, low serum acetylcholinesterase (> 50% of minimum
      normal value) supports the diagnosis of organophosphate poisoning but it does not
      show a significant relationship to the severity of poisoning (NS). The serum
      acetylcholinesterase activity may be a useful parameter in following the acute
      prognosis of organophosphate poisoning.

PMID- 12507061
TI  - Severe puff adder (Bitis arietans) envenomation with coagulopathy.
AB  - BACKGROUND: The puff adder (Bitis arietans) is a highly toxic venomous snake that
      is responsible for a large proportion of the venomous snakebites in sub-Saharan
      Africa, where it is indigenous. Puff adder bites in North America result from
      snakes in captivity. Although thrombolytic enzymes are present in puff adder
      venom, significant coagulopathy has not been previously reported with a confirmed
      puff adder envenomation. RESULTS: We report a serious puff adder envenomation to
      the finger, characterized by severe swelling, local tissue necrosis, hypotension,
      thrombocytopenia, severe coagulopathy, and hemorrhage. Fifteen vials of South
      Africa polyvalent antivenom were administered, beginning 4.5 hours post
      envenomation, with step-wise improvement in hematological abnormalities. Other
      treatments included vasopressors, ventilatory support, leeches, transfusion, and
      eventual digit amputation. After a prolonged hospital course, the patient had a
      good outcome. CONCLUSIONS: Puff adder envenomation causes tissue necrosis,
      hypotension, coagulopathy, thrombocytopenia, and spontaneous bleeding. Severe
      coagulopathy may occur. Physicians treating severe cases should be prepared to
      administer at least 15 vials of antivenom if needed.

PMID- 12507062
TI  - Pharmacy prescription dispensing errors reported to a regional poison control
      center.
AB  - OBJECTIVES: To identify the incidence, types, associations, and outcomes of
      pharmacy prescription dispensing errors reported to a regional poison control
      center. METHODS: Retrospective chart review over a 35-month period. RESULTS: Of
      77,992 drug exposures reported, there were 6450 unintentional therapeutic
      exposures. Forty were the result of pharmacy prescription dispensing errors. Of
      these, 20 (50%) were medication substitution errors (wrong drug), 17 (42.5%) were
      labeling errors (correct drug, wrong formulation or instructions), and 3 (7.5%)
      were compounding errors (incorrect liquid dilution or capsule preparation). Both
      compounding and labeling errors were significantly more likely than substitution
      errors to be order-of-magnitude amounts. Compounding errors were also
      significantly more likely than labeling errors to be order-of-magnitude amounts.
      Labeling errors were significantly more likely to be liquids prescribed to
      children than substitution errors. Compounding errors had significantly more
      serious outcomes compared with substitution or labeling errors. CONCLUSIONS:
      Substitution and labeling errors are the most common pharmacy prescription
      dispensing errors reported to a regional poison control center. Compounding
      errors have the greatest potential for serious outcomes. Children are
      particularly at risk because of the increased potential for error in the
      preparation and use of liquids. Inclusion of scenarios of prescription dispensing
      errors in the Toxic Exposure Surveillance System database would improve error
      detection and tracking. Poison control centers may be a source of valuable
      feedback to physicians and pharmacists.

PMID- 12507063
TI  - Gabapentin withdrawal presenting as status epilepticus.
AB  - A 34-year-old male with lumbar disc disease and surgery was placed on gabapentin
      daily for chronic back pain. He remained on a steady dose of 8000 mg/day for 9
      months, almost doubled what is considered therapeutic. He ran out of medication,
      was unable to refill his prescription for 2 days and presented to the emergency
      department in status epilepticus. There was no previous history of seizure
      disorder and he was on no other medications. A medical evaluation for an
      alternative etiology of his seizures was negative. Although gabapentin withdrawal
      has been previously reported and usually consists of anxiety, diaphoresis, and
      palpitations, this is the first reported patient with generalized seizures and
      status epilepticus secondary to gabapentin withdrawal.

PMID- 12507064
TI  - Fomepizole therapy for pediatric butoxyethanol intoxication.

PMID- 12507065
TI  - Acute hyponatremia, seizure, and rhabdomyolysis after ecstasy use.

PMID- 12507066
TI  - Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.
AB  - OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all
      pituitary tumors. The purpose of this retrospective study is to evaluate the
      efficacy and role of gamma knife radiosurgery (GKS) in the management of residual
      or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted
      of the data obtained in 42 patients who underwent adjuvant GKS at the University
      of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal
      resection, craniotomy and resection, or conventional radiotherapy.
      Endocrinological, ophthalmological, and radiological responses were evaluated.
      The duration of follow-up review varied from 6 to 102 months (mean 31.2 months).
      Fifteen patients were observed for more than 40 months. The mean radiation dose
      to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to
      restrict the dose to the optic nerve and chiasm. Tumor control after GKS was
      achieved in 100% of patients with microadenomas and 97% of patients with
      macroadenomas. Gamma knife radiosurgery was equally effective in controlling
      adenomas with cavernous sinus invasion and suprasellar extension. No patient
      developed a new endocrinological deficiency following GKS. One patient's tumor
      enlarged with an associated decline in visual function. Another patient
      experienced a deterioration of visual fields despite a decrease in tumor size.
      CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all
      residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates
      tumor management even when the adenoma is close to the optic apparatus or invades
      the cavernous sinus.

PMID- 12507067
TI  - Effects of gamma knife radiosurgery of pituitary adenomas on pituitary function.
AB  - OBJECT: The authors undertook a retrospective analysis of the incidence and time
      course of pituitary insufficiency following gamma knife radiosurgery (GKS) for
      pituitary adenomas. METHODS: Pituitary adenomas in 92 patients were analyzed.
      There were 61 hormonally inactive tumors, 18 prolactinomas, and nine somatotropic
      and four adrenocorticotropic adenomas. The mean tumor volume was 3.8 cm3 (range
      0.2-14.6 cm3). The mean prescription dose was 15 Gy. The mean prescription
      isodose was 50.7%. The mean follow-up time was 4.6 years (range 1.2-10 years).
      The following new or deteriorating insufficiencies that did not require treatment
      were recorded for the different pituitary axes: follicle-stimulating hormone
      (FSH)/ luteinizing hormone (LH) 19 (20.6%), thyroid-stimulating hormone (TSH) 32
      (34.8%), adrenocorticotropic hormone (ACTH) 10 (10.9%), and growth hormone (GH)
      26 (28.3%). For new insufficiencies or deterioration requiring replacement
      therapy, the figures were as follows: FSH/LH 20 (21.7%), TSH 22 (23.9%), ACTH
      eight (8.7%), and GH 12 (13%). Spot dosimetry was performed in 59 patients in the
      hypothalamic region, the pituitary gland, and pituitary stalk. The pituitary
      stalks in patients with deterioration of pituitary function received a
      statistically higher dosage of radiation, 7.7 +/- 3.7 Gy compared with 5.5 +/- 3
      Gy (p = 0.03). CONCLUSIONS: The function of the residual normal pituitary gland
      is less affected following GKS of pituitary adenomas than after fractionated
      radiotherapy. Nonetheless, increased attention needs to be exercised to reduce
      the dose to the stalk and pituitary gland to minimize the incidence of these
      complications.

PMID- 12507068
TI  - Gamma knife radiosurgery in the treatment of Cushing disease: long-term results.
AB  - OBJECT: The authors sought to analyze the long-term outcome of patients with
      Cushing disease who underwent gamma knife radiosurgery (GKS) as either an
      adjuvant or primary treatment. METHODS: Twenty-five patients with Cushing disease
      were treated by OKS and followed for more than 2.5 years (mean 5.3 years). The
      overall results showed a complete response rate of 30%, a response rate of 85%,
      and a tumor control rate of 100%. Tumor size and radiation dose were the most
      important factors related to the treatment response. The complete response rate
      for microadenomas and small adenomas was significantly higher than that for
      macroadenomas. An 83.2% complete response rate was obtained using a maximum dose
      of more than 55 Gy and/or a margin dose of more than 40 Gy. Serum
      adrenocorticotropic hormone and cortisol levels were normalized in 35% of
      patients, decreased significantly in 60%, and decreased in 85%. Fifty-one of 85
      characteristic signs and symptoms of Cushing disease improved without any side
      effects. The overall outcome was excellent in seven cases, good in six, fair in
      four, and poor in four cases; one patient died. The initial treatment was GKS in
      four patients, two of whom had a complete response and two of whom had a partial
      response. Hormone levels returned to normal in the patients in whom there was a
      complete response. The results in the six patients in whom Nelson syndrome was
      present were less favorable; the response rate was only 33%, although the control
      rate was 100%. Hormone levels decreased in two patients. CONCLUSIONS: Gamma knife
      radiosurgery is safe and effective for the treatment of Cushing disease as an
      adjuvant or initial therapy when selective and accurate dose planning is
      performed.

PMID- 12507069
TI  - Efficacy of gamma knife radiosurgery for nonfunctioning pituitary adenomas: a
      quantitative follow up with magnetic resonance imaging-based volumetric analysis.
AB  - OBJECT: The authors assessed the efficacy of gamma knife radiosurgery (GKS) for
      nonfunctioning pituitary adenomas (NPAs) by sequential quantitative
      determinations of tumor volume and neurological and endocrinological follow-up
      examinations. METHODS: Through May of 2000, 45 patients with NPA were treated by
      GKS. Complete neurological and endocrinological follow-up information was
      obtained. In 30 patients (67%), follow-up examinations included stereotactic
      magnetic resonance imaging involving the GammaPlan software for sequential
      measurements of the NPA volume. These patients constitute the basis of this
      study. Sequential volume measurements after GKS were compared with initial tumor
      volumes at the date of GKS to quantify the therapeutic result. All data were
      stored prospectively in a computerized database. The median dose to the tumor
      margin was 16 Gy (range 11-20 Gy). The mean prescription isodose was 55% (range
      45-75%). All except one patient (97%) underwent surgery for NPA before GKS.
      Fractionated radiotherapy was not administered. Median follow up after GKS was 55
      months (range 28-86 months). The actuarial long-term recurrence-free survival was
      93% with respect to a single GKS and 100% if a repeated GKS was included.
      Neurological side effects were not detected. The actuarial risk of radiosurgery
      induced pituitary damage was calculated to be 14% after 6 years. The volumetric
      analysis revealed a temporary swelling of the NPA in four patients, followed by
      shrinkage of the lesion. This is the first time this has been observed in
      pituitary adenomas. CONCLUSIONS: Postoperative GKS for residual or recurrent
      small fragments of NPAs is effective and safe. With regard to the issues of
      radioprotection and therapeutic morbidity, it seems superior to fractionated
      radiotherapy. Quantification of tumor reduction is a valuable tool for
      documenting a therapeutic response and for identifying tumor recurrence. As part
      of a radiosurgical standard protocol, the follow-up examination for NPAs should
      include tumor volumetric analysis.

PMID- 12507070
TI  - Gamma knife surgery for cancer pain-pituitary gland-stalk ablation: a multicenter
      prospective protocol since 2002.
AB  - OBJECT: The authors have treated intractable pain, particularly cancer pain
      related to bone metastasis, with various protocols. Cancer pain has been treated
      by gamma knife radiosurgery (GKS), targeted to the pituitary gland-stalk, as an
      alternative new pain control method. The purpose of this study was to investigate
      a prospective multicenter protocol to prove the efficacy and the safety of this
      treatment. METHODS: Indications for patient inclusion in this treatment protocol
      were: 1) pain related to bone metastasis; 2) no other effective pain treatment
      options; 3) general condition rated as greater than 40 on the Kamofsky
      Performance Scale; 4) morphine effective for pain control; and 5) no previous
      treatment with radiation (GKS or conventional radiotherapy) for brain metastasis.
      The authors at one institution have treated two patients, who suffered from
      severe cancer pain related to bone metastasis, by using GKS. The target was the
      pituitary gland. The maximum dose was 160 Gy with one isocenter of an 8-mm
      collimator, keeping the radiation dose to the optic nerve less than 8 Gy. At
      another institution two patients were treated in the same way; an additional five
      patients were treated similarly with targeting of the pituitary gland with two
      isocenters of 4-mm collimator. In all nine cases, pain resolved without
      significant complication. Pain relief was observed within several days, and this
      effect was prolonged until the day that they died. At a follow up of 1 to 24
      months, no recurrences and no hormonal dysfunction were observed. CONCLUSIONS:
      Despite insufficient experience, the efficacy and the safety of GKS for
      intractable pain were demonstrated in nine patients. This treatment has the
      potential to ameliorate cancer-related pain, and GKS will play a more important
      role in the treatment of intractable pain. More experience and additional refined
      study protocols are needed to evaluate which parameters are important, to
      determine what treatment strategy is the best, and to clarify the safest option
      for patients with intractable cancer pain.

PMID- 12507071
TI  - Successful treatment of spindle cell sarcoma of the sella turcica. Case report.
AB  - A primary spindle cell sarcoma of the sella turcica in a patient without a
      history of radiation treatment is a very rare occurrence. Only one other case has
      been reported to date, with local recurrence 7 months after the patient underwent
      subtotal resection and stereotactic radiosurgery of the tumor. The authors
      present a case of spindle cell sarcoma of the sella turcica successfully treated
      by surgery, external-beam radiotherapy, and gamma knife radiosurgery. After 24
      months of follow up, the patient continues to show no evidence of disease.

PMID- 12507072
TI  - Carcinomatous meningitis: are surgeryand gamma knife radiosurgery treatment risk
      factors?
AB  - OBJECT: The purpose of this study was to identify possible risk factors leading
      to carcinomatous meningitis in patients with a known brain metastasis and who
      were treated with gamma knife radiosurgery (GKS). METHODS: Two hundred eighty
      lesions in 101 patients were treated during 121 GKS procedures. The clinical and
      neuroimaging history, tumor histology, and follow-up studies were reviewed for
      all patients. Evidence as demonstrated by magnetic resonance imaging criteria
      and/or cerebrospinal fluid (CSF) cytology of carcinomatous meningitis was
      evaluated. The data were then analyzed to identify potential risk factors for the
      development of CSF dissemination. CONCLUSIONS: It appears that carcinomatous
      meningitis is exclusively identified in patients with adenocarcinoma, in
      particular with primary lung cancer. Furthermore, the incidence is higher if
      surgery is performed and the interval to subsequent GKS is prolonged.

PMID- 12507073
TI  - Effect of subpixel magnetic resonance imaging shifts on radiosurgical dosimetry
      for vestibular schwannoma.
AB  - OBJECT: The purpose of this study was to evaluate subpixel magnetic resonance
      (MR) imaging shifts of intracanalicular vestibular schwannomas (VSs) with respect
      to the internal auditory canal (IAC) as documented on computerized tomography
      (CT) scanning and to investigate the source of imaging-related localization
      errors in radiosurgery as well as the effect of such shifts on the dosimetry for
      small targets. METHODS: A shift of the stereotactic coordinates of
      intracanalicular VSs between those determined on MR imaging and those on CT
      scanning represents an error in localization. A shift vector places the tumor
      within the IAC and measures the CT scan/MR image discrepancy. The shift vectors
      were measured in a series of 15 largely intracanalicular VSs (all < 1.5 cm3 in
      volume). Using dose volume histogram measurements, the overlap between shifted
      and unshifted tumors and radiosurgical treatment plans were measured. Using
      plastic and bone phantoms and thermoluminescent dosimetry measurements, the
      correspondence between CT and MR imaging targets and treatments delivered using
      the Leksell gamma knife were measured. Combining these measurements, the
      correspondence between intended and actual treatments was measured. CONCLUSIONS:
      The delivery of radiation to CT-imaged targets was accurate to the limits of
      measurement (approximately 0.1 mm). The MR imaging shifts seen in the y axis
      averaged 0.9 mm and in the z axis 0.8 mm. The corresponding percentage of tumor
      coverage with respect to apparent target shift decreased from 98 to 77%. This
      represents a significant potential error when targets are defined solely by MR
      imaging.

PMID- 12507074
TI  - Gamma knife model C with the automatic positioning system and its impact on the
      treatment of vestibular schwannomas.
AB  - OBJECT: The aim of this study was to assess the effects of the gamma knife
      automatic positioning system (APS) on the treatment of patients, particularly
      effects of this system on the treatment of patients with vestibular schwannomas
      (VSs), with a view to reducing loss of hearing. METHODS: The dose delivery with
      an increased number of shots was checked with GAFChromic Film for various numbers
      of shots (one to 129). The results in the first 549 patients were recorded. In
      addition a series of 59 patients with VSs treated with 13 Gy to the 65% isodose
      is presented. The authors have termed this the "13 on 65" concept. The film
      dosimetry showed that a large number of small shots did not materially affect the
      dose and dose distribution produced by gamma knife treatment. The APS was used
      alone in 72% of arteriovenous malformations, 71% of meningiomas, 94% of VSs, and
      84% of pituitary adenomas. Metastatic tumors were accessible in a pure APS mode
      in 59% of all cases, glioma in 58%, and uveal melanoma in 10% of the cases. Thus
      two thirds of patients could be treated using APS alone. It was possible to use
      the APS and manual systems together for complex or very eccentrically placed
      targets. The APS resulted in the use of a larger number of isocenters. After a
      mean follow-up period of 15 months, the results in patients with the VSs in whom
      13 Gy was delivered to the 65% isodose were similar to those in patients treated
      with the more conventional 50% margin isodose. There was no change in the
      incidence of hearing loss within the study period, and the incidence of
      trigeminal and facial neuropathies remained unchanged after treatment as well.
      CONCLUSIONS: The APS encourages the design of more conformal dose plans. The
      greater use of smaller collimators results in a steeper dose gradient with a
      smaller amount of radiation outside the target volume. Because the APS is able to
      apply a large number of smaller isocenters in an acceptable time, the number of
      isocenters used is increased. An increased number of isocenters can also be used
      to reduce the maximum radiation dose and increase the homogeneity in a given dose
      plan.

PMID- 12507075
TI  - Gamma knife radiosurgery for jugular foramen schwannomas.
AB  - OBJECT: The purpose of this study was to evaluate the effect on tumor growth and
      symptom relief in patients with jugular foramen schwannomas after undergoing
      gamma knife radiosurgery (GKS). METHODS: Between November 1993 and December 2000,
      27 patients were treated for jugular foramen schwannomas. The results of GKS in
      these cases are reviewed. Twelve patients had undergone previous tumor resection
      and the others underwent GKS as their primary treatment. The mean tumor volume
      was 13.5 cm3 (range 4.7-35.7 cm3). The mean margin dose was 14.6 Gy (range 9.8-20
      Gy). The mean maximum dose was 32.6 Gy (range 25.4-50 Gy). The prescription
      isodose was 35 to 55%. Twenty-five patients were followed for a mean period of
      38.7 months (range 9-90 months). Tumors shrank in 11 patients, remained stable in
      13, and enlarged in one patient who underwent a second GKS procedure. Sixteen
      patients improved and nine remained at their pre-GKS clinical status. No patient
      developed new cranial nerve deficits after GKS. CONCLUSIONS: The follow-up
      results indicate that GKS is a safe and effective primary or adjuvant treatment
      method for the control of jugular foramen schwannomas.

PMID- 12507076
TI  - Effect of a single high-dose gamma irradiation on cultured cells in human
      cerebral arteriovenous malformation.
AB  - OBJECT: The purpose of this study was to analyze the effect of single high-dose
      gamma irradiation at a cellular biological level on tissue cultures obtained in
      patients who underwent surgery for cerebral arteriovenous malformation (AVM).
      METHODS: The cell proliferation indices and changes in activation of p53, p21Waf
      1, and mdm-2 were determined. Additionally, immunohistochemical investigations
      for vimentin, desmin, alpha-smooth muscle actin (alpha-SMA), glial fibrillary
      acidic protein, Factor VIII-related antigen (F-VIII), cytokeratin, S100, and
      transforming growth factor-beta (TGFbeta) were performed on cultured AVM cells
      after a single high-dose irradiation. Normal human brain microvessel endothelial
      (HBE) cells and aortic smooth muscle cells served as controls. The proliferation
      index decreased on the 5th day after irradiation and remained depressed over the
      observation period in the irradiated AVM cultures. The p53, p21Waf-1, and mdm-2
      messenger RNA measurements showed considerable elevation both in AVM cultures and
      HBE cells after 15-Gy irradiation, which indicated apoptosis.
      Immunohistochemistry revealed strong vimentin positivity in the nonirradiated
      cultures, which gradually decreased in the irradiated cultures. Transforming
      growth factor-beta positivity was demonstrated in the irradiated specimens,
      indicating transformation of fibroblastic cells into activated myofibroblastic
      elements. This transformation was confirmed by demonstrating elevated SMA
      expression as well in the radiation-treated fibroblasts. CONCLUSIONS: The
      presence of TGFbeta and alpha-SMA activity in the irradiated AVM cells suggests
      that along with the genetically confirmed apoptotic activity, fibroblast
      transformation into myofibroblasts might be one of the mechanisms leading to
      shrinkage and obliteration of AVMs after single high-dose gamma irradiation.

PMID- 12507077
TI  - Can magnetic resonance imaging alone accurately define the arteriovenous nidus
      for gamma knife radiosurgery?
AB  - OBJECT: Current radiosurgical treatment of arteriovenous malformations (AVMs)
      relies on planning protocols that integrate data from both magnetic resonance
      (MR) imaging and stereotactic angiography studies. Angiography, however, is
      invasive and associated with a small but well-defined risk of neurological and
      systemic complications. Magnetic resonance imaging, on the other hand, is
      noninvasive with multiplanar capability, demonstrates good anatomical detail, and
      has been shown to be superior to angiography in the delineation of selected AVMs.
      METHODS: In this study, MR imaging-related accuracy of defining the AVM nidus in
      gamma knife radiosurgery is investigated using only T1- and T2-weighted
      sequences. CONCLUSIONS: Little interobserver variability was observed and AVM
      nidi, as demonstrated on T1- and T2-weighted MR images, were well correlated in
      terms of size. The displacement of the new target, however, from the original
      nidus, was not predictable and occasionally was significant, thus precluding safe
      radiosurgical planning.

PMID- 12507078
TI  - Impact on the quality of life of patients with arteriovenous malformations during
      the latent interval between gamma knife radiosurgery and lesion obliteration.
AB  - OBJECT: The aim of this study was to measure the quality of life (QOL) in
      patients with cerebral arteriovenous malformations (AVMs) receiving gamma knife
      treatment before total AVM obliteration. Quality of life was assessed as it
      related to the knowledge of rebleeding risk during the waiting period, AVM
      symptoms, and previous bleeding. METHODS: Thirty-nine patients age 18 years or
      older without other medical problems were asked to complete a questionnaire that
      included demographic variables, immediate effect of gamma knife radiosurgery,
      symptoms of AVM, previous hemorrhage, and the Duke-University of North Carolina
      Health Profile (63 items). CONCLUSIONS: The QOL of patients with cerebral AVM
      during the waiting period after undergoing gamma knife treatment was affected by
      irreversible physical disabilities rather than the knowledge of hemorrhage risk
      and bleeding experience.

PMID- 12507079
TI  - Hemorrhage risks and obliteration rates of arteriovenous malformations after
      gamma knife radiosurgery.
AB  - OBJECT: The purpose of this study was to analyze the risk of hemorrhage and the
      obliteration rate after treatment of patients with arteriovenous malformations
      (AVMs). METHODS: Between 1991 and 1995, 115 patients were treated using gamma
      knife radiosurgery (GKS). Surgical planning was based on angiograms and three
      dimensional images. The angiographic features of the AVMs and the risk factors
      for hemorrhage were then evaluated. Hemorrhages occurred in eight patients (7%) 7
      to 42 months after GKS. Based on AVM morphology, the rates of hemorrhage were
      five (7.6%) of 66 for AVMs with a single draining vein, seven (14%) of 66 for
      AVMs with deep drainage, four (26.7%) of 15 for AVMs with a varix, four (28.6%)
      of 14 for AVMs with venous obstruction, eight (17.0%) of 47 for high-flow (shunt-
      and mixed-type) AVMs, and five (35.7%) of 14 for large AVMs with a volume of more
      than 10 cm3. No hemorrhages were observed in association with low-flow (moyamoya
      type) AVMs in this series. Total AVM obliteration was achieved in 81.3% of 80
      patients who underwent angiography. The obliteration rate was 91.3% for
      moyamoyatype AVMs and 67.6% for shunt- and mixed-type AVMs. Early obliteration
      within 12 months was achieved in 63% of the moyamoya-type AVMs. CONCLUSIONS:
      Moyamoya-type AVMs seem to be at risk for post-GKS hemorrhage. Intravascular
      embolization should be considered prior to GKS for mixed- and shunt-type AVMs in
      an attempt to reduce the hemodynamic stress and thereby decrease the risk of
      hemorrhage.

PMID- 12507080
TI  - Gamma knife radiosurgery for cavernous hemangiomas in the cavernous sinus. Report
      of three cases.
AB  - A cavernous hemangioma occurring in the cavernous sinus is a rare vascular tumor
      that causes cranial nerve symptoms by direct compression. Surgical removal is
      often difficult because excessive intraoperative bleeding is expected. These
      lesions remain a therapeutic challenge even with state-of-the-art treatment
      modalities. The authors report three cases of cavernous hemangioma occurring in
      the cavernous sinus that were treated with gamma knife radiosurgery, with a mean
      patient age of 66 years and a mean tumor volume of 2.3 cm3.

PMID- 12507081
TI  - Stereotactic radiosurgery for dural arteriovenous fistula involving the superior
      sagittal sinus. Case report.
AB  - The authors present a case of ruptured dural arteriovenous fistula primarily
      draining into the superior sagittal sinus, which was successfully treated by
      gamma knife radiosurgery.

PMID- 12507082
TI  - Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a
      comparison between small cell and non-small cell carcinoma.
AB  - OBJECT: The purpose of this retrospective study was to evaluate the effectiveness
      of gamma knife radiosurgery (GKS) for the treatment of metastatic brain tumors
      from lung cancer, with particular reference to small cell lung carcinoma (SCLC)
      compared with non-SCLC (NSCLC). METHODS: Two hundred forty-five consecutive
      patients meeting the following five criteria were evaluated in this study: 1) no
      prior brain tumor treatment; 2) 25 or fewer lesions; 3) a maximum of three tumors
      with a diameter of 20 mm or larger; 4) no surgically inaccessible tumor 30 mm or
      greater in diameter; and 5) more than 3 months of life expectancy. According to
      the same treatment protocol, large tumors (> or = 30 mm) were surgically removed
      and the other small lesions (< 30 mm) were treated with GKS. New lesions were
      treated with repeated GKS. Chemotherapy was administered, according to the
      primary physician's protocol, as aggressively as possible. Progression-free,
      overall, neurological, qualitative, and new lesion-free survival were calculated
      with the Kaplan-Meier method and were compared in the SCLC and NSCLC groups by
      using the log-rank test. The poor prognostic factors for each type of survival
      were also analyzed with the Cox proportional hazard model. CONCLUSIONS: Tumor
      control rate at 1 year was 94.5% in the SCLC group and 98% in the NSCLC group.
      The median survival time was 9.1 months in the SCLC group and 8.6 months in the
      NSCLC group. The 1-year survival rates in the SCLC group were 86.5% for
      neurological survival and 68.9% for qualitative survival; those in the NSCLC
      group were 87.9% for neurological and 78.9% for qualitative survival. The
      estimated median interval to emergence of a new lesion was 6.9 months in the SCLC
      group and 9.8 months in the NSCLC group. There was no significant difference
      between the two groups for any type of survival; this finding was verified by
      multivariate analysis. The results of this study suggest that GKS appears to be
      as effective in treating brain metastases from SCLC as for those from NSCLC.

PMID- 12507083
TI  - Gamma knife radiosurgery for renal cell carcinoma brain metastases.
AB  - OBJECT: The purpose of this study was to clarify the effectiveness of gamma knife
      radiosurgery (GKS) in achieving a partial or complete remission of so-called
      radioresistant metastases from renal cell carcinoma (RCC) and to propose
      guidelines for optimal treatment METHODS: During a 5-year period, 29 patients (19
      male and 10 female) with 92 brain metastases from RCC underwent GKS. The median
      tumor volume was 4.7 cm3 (range 0.5-14.5 cm3). Fourteen patients (48%) also
      underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%)
      after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was
      16.8 Gy (range 13-30 Gy). All cases were categorized according to the Recursive
      Partitioning Analysis (RPA) classification for brain metastases. Univariate
      analysis was performed to determine significant prognostic factors and survival.
      The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky
      Performance Scale score, and controlled primary disease were not predictors of
      survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3
      months for RPA Classes I, II, and III, respectively, compared with the median
      survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone.
      CONCLUSIONS: These results suggest that WBRT combined with GKS may improve
      survival in patients with brain metastases from RCC. Furthermore, this
      improvement in survival was seen in all RPA classes.

PMID- 12507084
TI  - Gamma knife radiosurgery for intracranial metastatic melanoma: a 6-year
      experience.
AB  - OBJECT: The purpose of this study was to evaluate retrospectively the
      effectiveness of stereotactic radiosurgery for intracranial metastatic melanoma
      and to identify prognostic factors related to tumor control and survival that
      might be helpful in determining appropriate therapy. METHODS: Twenty-four
      patients with intracranial metastases (115 lesions) metastatic from melanoma
      underwent radiosurgery. In 14 patients (58.3%) whole-brain radiotherapy (WBRT)
      was performed, and in 12 (50%) chemotherapy was conducted before radiosurgery.
      The median tumor volume was 4 cm3 (range 1-15 cm3). The mean dose was 16.4 Gy
      (range 13-20 Gy) prescribed to the 50% isodose at the tumor margin. All cases
      were categorized according to the Recursive Partitioning Analysis classification
      for brain metastases. Univariate and multivariate analyses of survival were
      performed to determine significant prognostic factors affecting survival. The
      mean survival was 5.5 months after radiosurgery. The analyses revealed no
      difference in terms of survival between patients who underwent WBRT or
      chemotherapy and those who did not. A significant difference (p < 0.05) in mean
      survival was observed between patients receiving immunotherapy or those with a
      Karnofsky Performance Scale (KPS) score of greater than 90. CONCLUSIONS: The
      treatment with systemic immunotherapy and a KPS score greater than 90 were
      factors associated with a better prognosis. Radiosurgery for melanoma-related
      brain metastases appears to be an effective treatment associated with few
      complications.

PMID- 12507085
TI  - Survival and pattern of failure in brain metastasis treated with stereotactic
      gamma knife radiosurgery.
AB  - OBJECT: Gamma knife radiosurgery (GKS) has become a well-established treatment
      modality in the management of selected patients with brain metastasis. The
      authors review the management patients with these tumors treated at a single
      center. METHODS: Between 1994 and 2002, 458 consecutive patients with metastatic
      brain disease underwent GKS. There were 1305 lesions treated in 680 separate
      sessions. The histological diagnosis was melanoma in 231 (50%), lung cancer in 94
      (20.5%), breast cancer in 38 (8.3%), renal cell carcinoma (RCC) in 29 (6.3%),
      colon carcinoma in 13 (2.8%), unknown primary site in 14 (3.1%), and other in 39
      patients (8.5%). The median tumor volume was 0.9 cm3 and the median volume
      treated was 2.3 cm3. The median radiation dose was 18 Gy prescribed to a median
      isodose of 60%; the median dose was 20 Gy in melanoma, sarcoma, and RCC. Whole
      brain radiotherapy (WBRT) either prior to or following GKS was performed in 114
      patients (25%). Follow up ranged from 3 to 84 months with a median of 9 months.
      The median survival for all patients was 9 months and depended on tumor
      histology. Survival ranged from 6 months for patients with colon carcinoma,
      unknown primary tumors, and other tumors to 17 months for those with breast
      cancer. Median survival in patients with melanoma was 8 months. In multivariate
      analysis Karnofsky Performance Scale score (< 70 vs > 70), status of systemic
      disease (yes vs no), histological diagnosis, and total intracranial tumor volume
      were the only significant factors influencing survival. The number of brain
      metastases (one-five), WBRT (yes vs no), and age were not significant. Pattern of
      failure was different in patients with melanoma compared with those with other
      diagnoses. Cause of death in patients with melanoma was in 50% of the cases due
      to systemic disease and in 42% due to central nervous system causes, whereas it
      was 70% for the former and 23% for the latter in patients with other diagnoses.
      The treatment was well tolerated with significant late toxicity requiring
      craniotomy for removal of a necrotic focus in only 20 patients (4.7%).
      CONCLUSIONS: Gamma knife radiosurgery provided an excellent palliation with low
      incidence of toxicity. A Phase III prospective randomized trial is required to
      define the role of WBRT in combination with GKS.

PMID- 12507086
TI  - Gamma knife radiosurgery and brain metastases: local control, survival, and
      quality of life.
AB  - OBJECT: The purpose of this paper was to describe the clinical outcome in
      patients with brain metastases who underwent gamma knife radiosurgery (GKS).
      METHODS: The authors retrospectively reviewed the clinical courses of 54 patients
      with brain metastases who underwent 62 GKS procedures. This series covered a 43
      month period. A total of 174 lesions were treated: 38 patients harbored solitary
      whereas 24 patients harbored multiple metastases. The authors assessed outcome by
      examining local disease control, survival, and quality of life. The overall local
      control rate was 85%; the mean time to failure of local control was 10.5 months;
      and median survival was 8.4 months. Median survival, evaluated by the log-rank
      test, was greater among patients with a single metastasis (p = 0.043), breast
      cancer (p = 0.021), and those who had undergone multiple GKS procedures for local
      failure (p = 0.009). The initial Karnofsky Performance Scale (KPS) score and
      whole-brain radiotherapy were not significantly related to median survival. The
      KPS scores tended to remain stable through the follow-up period. There were no
      morbidities or deaths attributable to the procedure. CONCLUSIONS: Results in this
      series suggest that GKS can be an effective tool for the control of brain
      metastases. A prospective investigation should be performed to validate trends
      seen in this retrospective study.

PMID- 12507087
TI  - Radiosurgery as palliation for brain metastases: a retrospective review of 72
      patients harboring multiple lesions at presentation.
AB  - OBJECT: The purpose of this study was to determine the outcome of palliative
      gamma knife radiosurgery (GKS) in a group of poor-risk patients with multiple
      brain metastases. METHODS: The medical records of 72 patients with multiple brain
      metastases treated with GKS between October 1993 and November 9, 2001, were
      reviewed retrospectively. All patients presented with more than 10 lesions. There
      were 26 men and 46 women. The median age was 60 years (range 24-84 years). There
      were 39 patients with lung cancer, 18 with breast cancer, nine with metastatic
      melanomas, two with metastatic renal cell carcinomas, and four with other primary
      tumors. A total of 147 treatment sessions were required to treat 1304 sites in 72
      patients. A mean of 10.4 isocenters per treatment was used. The mean tumor volume
      was 1.7 cm3. All patients had extracranial disease. The variables included in
      this study were the patient's Karnofsky Performance Scale score, age, sex, the
      radiation dose, initial number of lesions, and tumor volume and histopathology.
      CONCLUSIONS: Radiosurgery can be a powerful tool in the palliative management of
      advanced metastatic disease even in patients presenting with multiple brain
      metastases. A median of two outpatient treatments was required, allowing the
      advanced cancer patient to avoid protracted fractionated radiotherapy and to
      undergo other therapeutic treatment with an acceptable quality of life.

PMID- 12507088
TI  - Gamma knife radiosurgery for brain metastases: a primary therapeutic option.
AB  - OBJECT: The aim of this retrospective study was to assess the role of gamma knife
      radiosurgery (GKS) as a primary treatment for brain metastases by evaluating the
      results in particularly difficult cases such as oncotypes-which are unresponsive
      to radiation-cystic lesions, and highly critical locations such as the brainstem.
      METHODS: Treatment of 804 patients with 1307 solitary (29%), single (26%), and
      multiple (45%) brain metastases was evaluated. Treatment planning parameters were
      as follows: mean tumor volume 4.8 cm3 (range 0.01-21.5 cm3), mean prescription
      dose 20.6 Gy (range 12-29 Gy), and mean number of isocenters 6.5 (one-19). In
      unresponsive oncotypes such as melanoma and renal cell carcinoma, the mean target
      dosages were higher. Cystic metastatic lesions were initially stereotactically
      evacuated and then GKS was performed. Patients with brainstem metastases were
      treated with lower doses. Conventional radiotherapy was used in only a minority
      (14%) of selected cases. The overall median patient survival time was 13.5
      months, and the 1-year actuarial local progression-free survival rate was 94%,
      with a mean palliation index and functional independence index of 53.8 and 52.5
      weeks, respectively. The local tumor control rate was 93%, with a mean follow-up
      period of 14 months. In the overall series, and especially in the unresponsive
      oncotypes, systemic disease progression was the main limiting factor with regard
      to patient life expectancy. CONCLUSIONS: Gamma knife radiosurgery seems to be the
      primary treatment option for patients harboring small-to-medium size (< or = 20
      cm3) brain metastases with reasonable life expectancy and no impending
      intracranial hypertension. Results are better than with those obtained using
      whole-brain radiotherapy and comparable to the best selected surgery-radiation
      series, even in oncotypes unresponsive to therapeutic radiation, cystic tumors,
      and tumors located in the brain stem.

PMID- 12507089
TI  - Gamma knife radiosurgery for trigeminal neuralgia: the dry-eye complication.
AB  - OBJECT: The purpose of this paper is to report a unique complication of gamma
      knife radiosurgery (GKS) for trigeminal neuralgia (TN). The nature of this
      complication and its related factors are discussed. METHODS: Forty-one medically
      refractory patients with TN were treated with GKS. All patients received 80 Gy to
      the proximal trigeminal nerve root, using a 4-mm collimator and a single
      isocenter. Follow up consisted of three monthly outpatient sessions after GKS.
      Improvement, recurrence, complications, and changes in magnetic resonance imaging
      were recorded. To evaluate the factors behind the complications, a subgroup of 33
      patients was assessed in whom the follow-up duration was more than 9 months. The
      follow-up duration was 3 to 36 months (mean 13 months). The results were
      excellent in 20 patients, good in 11, and fair in seven. No patient had a poor
      result. Three patients suffered recurrences. Seven patients suffered
      complications 9 to 24 months after GKS. All seven patients complained of facial
      numbness and hypesthesia was recorded. Three of them also complained of "dry eye"
      with diminution or absence of corneal reflex but no other abnormalities of the
      cornea and conjunctiva were found on ophthalmological examination. In these three
      patients, hypesthesia of the first division of the trigeminal nerve area had been
      found before their "dry eye" symptoms appeared. The irradiated volume on the
      brainstem was significantly related to this complication. CONCLUSIONS: The dry
      eye symptom seems to be a special form of sensory disturbance. An overdose of
      radiation to the brainstem may play an important role in the manifestation of
      this complication.

PMID- 12507090
TI  - Gamma knife radiosurgery for trigeminal neuralgia associated with multiple
      sclerosis.
AB  - OBJECT: The authors assessed the efficacy and complications from gamma knife
      radiosurgery (GKS) for multiple sclerosis (MS)-associated trigeminal neuralgia
      (TN). METHODS: There were 15 patients with MS-associated TN (MS-TN). Treatment
      involved three sequential protocols, 70 to 90-Gy maximum dose, using a single 4
      mm isocenter targeting the ipsilateral trigeminal nerve at its junction with the
      pons with the 50% isodose. Pain was appraised by each patient by using Barrow
      Neurological Institute (BNI) Scores I through IV: I, no pain; II, occasional pain
      not requiring medication; IIIa, no pain but continued medication; IIIb, some
      pain, controlled with medication; IV, some pain, not controlled with medication;
      and V, severe pain/no pain relief. With a mean follow up of 17 months (range 6-38
      months), 12 (80%) of 15 patients experienced pain relief. Three patients (20%)
      reported no relief (BNI Score V). For responders, the mean latency from treatment
      to the onset of pain relief was 13 days (range 1-61 days). Maximal relief was
      achieved after a mean latency of 56 days (range 1-157 days). Five patients
      underwent a second GKS after a mean interval of 534 days (range 231-946 days).
      The mean maximum dose at this second treatment was 48 Gy. The target was
      unchanged from the first treatment. All five patients who underwent repeated GKS
      improved. Complications were limited to delayed facial hypesthesias. Two (13%) of
      15 patients experienced onset of numbness after the first GKS, as well as two of
      five patients following a second GKS. The patients found this mild and not
      bothersome. Each patient who developed hypesthesias also experienced complete
      pain relief. CONCLUSIONS: Gamma knife radiosurgery is an effective treatment for
      MS-TN. Radiosurgery carries an acceptable small risk of mild facial hypesthesias,
      and hypesthesia appears predictive of a favorable outcome.

PMID- 12507091
TI  - Unusual causes of trigeminal neuralgia treated by gamma knife radiosurgery.
      Report of two cases.
AB  - The purpose of this paper was to present two cases of secondary trigeminal
      neuralgia (TN) with an unusual origin and lesion location. In two cases TN was
      caused by lesions along the course of the trigeminal nerve within the pons and
      adjacent to the fourth ventricle. Both cases presented with typical TN. Brain
      magnetic resonance imaging revealed linear or wedge-shaped lesions adjacent to
      the fourth ventricle, extending anterolaterally and lying along the pathway of
      the intraaxial trigeminal fibers. The involvement of the nucleus of the spinal
      trigeminal tract and of the principal sensory trigeminal nucleus with segmental
      demyelination are suggested as possible causes for trigeminal pain in these
      cases. It is postulated that these lesions are the result of an old viral
      neuritis. The patients underwent gamma knife radiosurgery and their clinical
      responses have been encouraging to date.

PMID- 12507092
TI  - Gamma knife radiosurgery for recurrent trigeminal neuralgia.
AB  - OBJECT: Pain may fail to respond or may recur after initial gamma knife
      radiosurgery (GKS) for trigeminal neuralgia (TN). The authors examined their
      experience with performing a second GKS procedure in these patients. METHODS:
      Twenty-nine patients underwent repeated GKS for TN at our institution between
      March 1997 and March 2002. Questionnaires were mailed to patients to assess the
      degree of their pain relief and the extent of facial numbness. Nineteen patients
      responded. All patients underwent repeated GKS involving a single 4-mm isocenter
      directed at the trigeminal nerve as it exited the brainstem (mean maximum dose
      23.2 Gy). At a mean follow up of 13.5 months after the second procedure, 10
      patients (53%) were pain free and medication free. Four patients (21%) were pain
      free but elected to continue medication in reduced dose, and two patients (11%)
      had incomplete but satisfactory pain control and were still taking medication.
      There was new-onset facial numbness in eight patients (42%), rated as tolerable
      in all instances. CONCLUSIONS: Patients with facial numbness had a greater
      likelihood of being pain free than those with no sensory loss. The authors
      observed no cases of corneal anesthesia, keratitis, or deafferentation pain.

PMID- 12507093
TI  - Validity of stereotactic frame localization during radiosurgery after one
      fixation pin removal.
AB  - OBJECT: This study was designed to examine the effect on target localization of
      removing one fixation pin or post. METHODS: A stereotactic frame was applied to a
      head phantom by using four fixation pins. Contiguous axial computerized
      tomography (CT) slices (1 mm thick) were obtained through the head phantom. Using
      clinical treatment planning software, a marker was identified and its coordinates
      were determined. The imaging procedure and point localization were repeated
      independently seven times in the control configuration, after four-pin fixation,
      to study reproducibility. Standard deviations in marker coordinates were 0.013,
      0.046, and 0.039 mm along the x, y, and z axes, respectively, indicating
      excellent reproducibility. Each of the four pins was then removed separately,
      leaving three pins providing fixation to the skull. Imaging was repeated for each
      three-pin configuration. To simulate the forces at each pin-skull interface, a
      lever arm was connected to the head phantom allowing application of variable
      torque to the system. The CT scans were obtained for each torque strength and pin
      removal combination. Marker coordinates were compared with the control.
      CONCLUSIONS: In most cases, it was found that accurate target positioning could
      be achieved after removal of a single pin and/or post. When high torque was used,
      however, removal of a pin resulted in up to a 1.2-mm error. The findings may be
      significant for clinical practice, depending on the condition being treated.

PMID- 12507094
TI  - The integration of metabolic imaging in stereotactic procedures including
      radiosurgery: a review.
AB  - OBJECT: The authors review their experience with the clinical development and
      routine use of positron emission tomography (PET) during stereotactic procedures,
      including the use of PET-guided gamma knife radiosurgery (GKS). METHODS:
      Techniques have been developed for the routine use of stereotactic PET, and
      accumulated experience using PET-guided stereotactic procedures over the past 10
      years includes more than 150 stereotactic biopsies, 43 neuronavigation
      procedures, and 34 cases treated with GKS. Positron emission tomography-guided
      GKS was performed in 24 patients with primary brain tumors (four pilocytic
      astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic
      astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five
      patients with metastases (single or multiple lesions), and five patients with
      pituitary adenomas. CONCLUSIONS: Data obtained with PET scanning can be
      integrated with GKS treatment planning, enabling access to metabolic information
      with high spatial accuracy. Positron emission tomography data can be successfully
      combined with magnetic resonance imaging data to provide specific information for
      defining the target volume for the radiosurgical treatment in patients with
      recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This
      approach is particularly useful for optimizing target selection for infiltrating
      or ill-defined brain lesions. The use of PET scanning contributed data in 31
      cases (93%) and information that was specifically utilized to adapt the target
      volume in 25 cases (74%). It would seem that the integration of PET data into GKS
      treatment planning may represent an important step toward further developments in
      radiosurgery: this approach provides additional information that may open new
      perspectives for the optimization of the treatment of brain tumors.

PMID- 12507095
TI  - Experimentally determined three-dimensional dose distributions in small complex
      targets.
AB  - OBJECT: The purpose of the paper is to describe a workable three-dimensional
      dosimetry system for use in quality assurance programs of departments in which
      radiosurgery is performed. METHODS: A system was developed on the basis of
      radiochromatic films. The experimental findings of the measured dose
      distributions for small complex-shaped targets, within a specially designed
      phantom, are described and compared with the same parameters calculated from the
      corresponding dose plan. The following parameters were determined for 83 patients
      with irregularly shaped targets who underwent gamma knife radiosurgery (GKS):
      target volume; dose-volume histograms of the target; 12-Gy, 15-Gy, and 18-Gy
      volumes; dose plan conformity; dose fall profiles in all dimensions to 50% of the
      prescription dose; and a quality factor (QF) to evaluate the adequacy of a GKS
      plan or treatment. The precise function and accuracy of the developed measuring
      device is shown and it demonstrated the expected steep dose falloff outside the
      irregularly shaped targets in all directions. The dose falloff was of the order
      of > 3 Gy/mm and the values of the QF were in the range between 0.5 and 0.9.
      CONCLUSIONS: A comparison with data from the literature shows that at least for
      small targets (< 2 cm3 and < 2.5 cm3) simulated within a head phantom, the dose
      gradient is significantly steeper in all directions than when using alternative
      treatment devices in radiosurgery and the overall QF is superior in most of the
      cases.

PMID- 12507096
TI  - Application of polymer gel dosimetry in gamma knife radiosurgery.
AB  - OBJECT: The purpose of this study was to investigate the use of a polymer gel
      based dosimeter for the evaluation of geometric and dosimetric inaccuracies
      during gamma knife radiosurgery and during the irradiation of an experimental
      animal. METHODS: A polymer gel dosimeter, based on acrylic monomers, was used for
      experiments conducted in this study. The accuracy of the dosimeter was evaluated
      on a Siemens EXPERT 1-tesla scanner in the transmitter/receiver head coil with
      the use of a multiecho sequence with 16 echoes, TE 22.5 to 360 msec, TR 2000
      msec, slice thickness 2 mm, field of view 255 mm, and a pixel size of 0.5 x 0.5
      mm2. Two experiments were conducted. First, the head phantom containing the
      polymer gel dosimeter was irradiated using 4-, 8-, 14-, and 18-mm isocenters.
      Second, a specially designed rat phantom was irradiated by four 4-mm isocenters.
      The dose profiles in the x, y, and z axes were calculated in the treatment
      planning system and measured with the polymer gel dosimeter and the results were
      compared. There was good agreement between the measured and calculated dose
      profiles. The maximum deviation in the spatial position of the center of measured
      and calculated dose profiles was 0.5 mm in the head phantom and 1 mm in the rat
      phantom. The maximum deviation in the width of the selected reference isodose of
      measured profiles was 1.2 mm in the head phantom and 1.1 mm in the rat phantom.
      CONCLUSIONS: The use of the polymer gel-based dosimeter for the verification of
      stereotactic procedures has advantages compared with other dosimetric systems.
      The dosimeter itself is tissue equivalent. Three-dimensional dose distributions
      can be measured and the dosimeter allows simulation of the therapeutic
      procedures.

PMID- 12507097
TI  - A new magnetic resonance head coil and head immobilization device for gamma knife
      radiosurgery: an analysis of geometric distortion and signal/noise
      characteristics.
AB  - OBJECT: The authors report on a new head coil into which the Leksell aluminum
      localization frame can be easily and securely mounted. Mechanically, the head
      coil interferes little with the patient. METHODS: The head coil, which is for
      magnetic resonance (MR) imaging, is a 12-element quadrature transmit-and-receive
      high-pass birdcage coil with a nominal operation frequency (63.86 MHz). The coil
      was built into a plastic housing. This new head coil minimizes patient motion and
      provides a 20% increase in signal/noise ratios compared with standard head coils.
      An MR image test phantom was mounted in the coil and this allowed quantification
      of image distortion due to inhomogeneities in the main magnetic field,
      nonlinearity in the gradient field, and paramagnetism of the aluminum headframe.
      There were no significant differences in geometric distortion between the new
      head coil and the standard coil. CONCLUSIONS: The new head coil has advantages
      for reducing patient movement artifacts and has a better signal/noise ratio with
      no reduction in geometric accuracy.

PMID- 12507098
TI  - Rotational movements of the automatic positioning system under load and their
      significance for patient treatments.
AB  - OBJECT: During routine quality assurance (QA) testing of the gamma knife
      Automatic Positioning System (APS), it was noticed that slight pressure applied
      to the handle of the QA test tool produced visible rotation of the APS assembly.
      The authors describe the tests performed to quantify these movements. METHODS: A
      stereotactic frame was positioned in the slides of the APS and known loads
      applied using a spring balance to the upper corner of the frame. Movement at the
      corner of the frame (y = 200) was measured using a dial gauge. The typical load
      applied to the APS by a patient with a medium-sized head was determined in a
      treatment simulation. Projecting the measured data, a plot showing the resultant
      error in the position of a target point was constructed. Error values increased
      with distance from the frame, up to a maximum of 0.3 mm (at the superior limit of
      treatment range). Increased loads could be applied to the system during patient
      movements, and these would result in larger displacements. Two volunteers
      enlisted to simulate patient movements and the deflections were recorded. It was
      estimated that maximum errors in the target positioning of 0.45 mm might take
      place during these movements. CONCLUSIONS: The use of the APS has some additional
      and unexpected associated errors. The authors believe, however, that because the
      errors are smaller than those of target localization and manual trunnion
      treatments, its clinical use is still justified. The manufacturer is
      investigating the cause of the movements and possible solutions.

PMID- 12507099
TI  - The commissioning and quality assurance of the Automatic Positioning System on
      the Leksell gamma knife.
AB  - OBJECT: The authors describe a series of commissioning checks that were developed
      following the installation of the Automatic Positioning System (APS) on the model
      C gamma knife. METHODS: System reliability was checked by performing a series of
      test treatments using the APS. A phantom was designed to enable the exposure of
      small pieces of Gaf Chromic film at 40 different predefined x, y, and z
      coordinates. The phantom consisted of a base plate with a series of film holders
      to facilitate the exposures using a 4-mm field, the center of which was marked. A
      spreadsheet calculation was performed to verify the conversion from Leksell
      coordinates to the APS coordinates when the treatment angle (gamma angle) is
      other than 90 degrees. A number of APS plans were prepared and the coordinate
      transformation verified. Precision measurements were performed to verify the
      correct positioning of the high bars when attached to the frame. The Gaf Chromic
      films were exposed, and the APS plans were used when confined to positions within
      the high bar range. A test tool to verify accurate location of the high bars on
      the frame was also designed. CONCLUSIONS: The performance of APS was verified
      independently of the manufacturer by using specially designed tools, phantoms,
      and spread sheets. At all points tested, the positional accuracy was found to be
      within specification. Conversion to APS coordinates was verified as correct.

PMID- 12507100
TI  - The clinical application of plugging patterns for the Leksell gamma knife.
AB  - OBJECT: In this report the authors explore the use of standardized plugging
      templates in formulating stereotactic radiosurgery dose plans for the Leksell
      gamma knife. METHODS: Unplugged gamma knife dose plans previously used in the
      treatment of patients with trigeminal neuralgia (TN) and vestibular schwannoma
      (VS) were studied. Standardized plugging templates were then superimposed on
      these plans, and their effects on the conformity index of tumors and the
      transposition of the radiation field from the brainstem to the cerebrospinal
      fluid spaces for the trigeminal cases were examined. CONCLUSIONS: The
      standardized plugging templates significantly increased the conformity indices in
      cases of VS plans and for TN. Plugging significantly reduced the brainstem
      exposure to radiation while at the same time not altering the length of the
      trigeminal nerve being treated. Standardized plugging templates may therefore be
      a useful tool in optimizing dose plans.

PMID- 12507101
TI  - Three-dimensional dose verification using BANG gel: a clinical example.
AB  - OBJECT: The authors sought to demonstrate the possible value of three-dimensional
      dose verification by using gel dosimetry. METHODS: In this study, commercially
      available BANG-25 Gy gel was used. This polymer gel is tissue equivalent and the
      relaxation rate (R2) measured using magnetic resonance (MR) imaging is
      proportional to the absorbed dose in the gel. A cylindrical container filled with
      BANG was mounted within an anthropomorphic head phantom and was handled using the
      same process as would be used for a patient undergoing gamma knife radiosurgery
      (GKS). An irregular target outline was constructed and a dose plan was created
      consisting of seven shots, three using the 8-mm and four using the 4-mm
      collimator helmet. The maximum dose specified was 25 Gy. A combination of several
      single spin-echo MR imaging sequences with different echo times was used to
      calculate the R2. The geometric resolution of the MR images was approximately 1
      mm3. To compare the measured dose distribution with the calculated one, isodoses
      were overlaid in three orthogonal planes by using specially designed analysis
      software. CONCLUSIONS: Comparisons of the measured and calculated relative dose
      distributions showed good overall agreement, with differences of less than 3 mm
      between measured and calculated isodoses. High resolution BANG gel dosimetry for
      GKS can be useful for the verification of clinical treatment plans, especially
      when multiple shots are involved. Further verifications will be done using
      additional imaging parameters and absolute dose calibrations to improve the
      method.

PMID- 12507102
TI  - Impact of the model C and Automatic Positioning System on gamma knife
      radiosurgery: an evaluation in vestibular schwannomas.
AB  - OBJECT: The technical advances associated with the model C gamma knife include a
      robotized system enabling automatic positioning of the stereotactic coordinates.
      The purpose of this study was to analyze the clinical impact of this technical
      modification. METHODS: The authors studied a sample of patients with vestibular
      schwannoma (VS). This sample included three groups treated using gamma knife
      radiosurgery. Group I comprised 21 patients with VS treated just before the
      installation of the Automatic Positioning System (APS). Group II included
      patients in Group I with new dose plans created using the APS (in other words,
      simulated dose plans). Group III consisted of a control group of 20 patients
      matched for tumor grade with the previous group and treated recently with the
      APS. Treatment times were calculated after correcting the time for each shot
      according to the age of the sources after reloading. The treatment times,
      including total time, irradiation time, and duration of the neurosurgical
      procedure, were analyzed. In addition, dose planning including number of
      isocenters, number of different collimators, malfunctions, and the conformity and
      selectivity indices were recorded. The trend was to reduce the mean number of
      collimator runs from 7.9 to 1.2 and to increase the mean number of shots from 7.9
      to 15.6, mostly by using the 4-mm collimator exclusively. The APS-related
      conformity and selectivity were improved from 95 to 97% and from 78 to 84%,
      respectively. The total treatment time was reduced by 53%, and time required to
      interact with the patient in the room was considerably reduced (75%), giving the
      neurosurgeon greater freedom to perform other tasks during the treatment period.
      The reduction of the time spent by the neurosurgeon at work in the room was 84%.
      The total radiation time was increased by 54%. CONCLUSIONS: The preliminary
      results of this study indicate that the robotization of the gamma knife is likely
      a major advance in radiosurgery.

PMID- 12507103
TI  - Gamma knife subthalamotomy for Parkinson disease: the subthalamic nucleus as a
      new radiosurgical target. Case report.
AB  - The authors present the neuroimaging, treatment planning, and radiosurgical
      technique for the first reported case of unilateral radiosurgical subthalamotomy,
      which was performed to control motor symptoms associated with advanced Parkinson
      disease (PD) in a patient who had undergone previous contralateral radiofrequency
      (RF) pallidotomy. A 73-year-old woman with end-stage PD had undergone RF
      pallidotomy of the right globus pallidus with resolution of symptoms. Two years
      following this procedure, due to the natural progression of her disease, she
      suffered recurrent motor fluctuations, dyskinesia, and worsening bradykinesia of
      the right side. Her Parkinson's Disease Disability Rating (PDDR) score was 28.
      Computerized tomography and magnetic resonance (MR) imaging were used to localize
      the left subthalamic nucleus (STN). The patient underwent gamma knife
      radiosurgery-a single shot of 120 Gy was administered using the 4-mm collimator
      helmet. The patient was evaluated up to 42 months after the procedure. The
      dyskinesia became minimal. Right-sided motor control improved as did her balance.
      At 3 months after treatment MR imaging demonstrated the radiosurgical lesion in
      the left STN. At 3.5 years postradiosurgery, she experienced minimal focal (oral)
      dyskinesia, no bradykinesia or rigidity, and her PDDR score was 11. Radiosurgery
      of the STN in this case was safe and effective. The STN is a readily localized
      anatomical target with neuroimaging. Radiosurgery avoids the risks of open
      procedures.

PMID- 12507104
TI  - Thalamic lesions produced by gamma thalamotomy for movement disorders.
AB  - OBJECT: The treatment of Parkinson disease and other kinds of involuntary
      movement by gamma knife radiosurgery (GKS) is presented. This is an extension of
      previous work. The clinical course and thalamic lesions were the main factors
      examined. METHODS: Seventeen new cases were added to the previously reported 36
      cases. The course and results for the whole series of 53 patients were examined.
      Treatment was undertaken using a single 4-mm collimator shot to deliver 130 Gy to
      the target. The target was determined in the previously treated patients by using
      classic methods involved in conventional stereotactic thalamotomy with
      microrecording. More recently, target localization has been performed by relating
      the target point to the total length of the thalamus. Points may then be defined
      as percentages of that length measured from the anterior pole. Targets can then
      be determined in relationship to the appropriate percentage. Thirty-five patients
      have been followed for more than 2 years and the longest follow up was 8 years.
      Two kinds of thalamic lesion were seen after GKS. Volumetric analysis on MR
      imaging revealed that the larger lesion was 400 to 500 mm3 at the beginning and
      gradually decreased in size. The smaller lesion occupied approximately 200 mm3
      and also shrank over several months. Eighty percent of the treated cases showed
      good results and no significant complications, with the tremor subsiding at 1
      year (Type 1). Several cases deviated from this standard course in four different
      ways (Types 2-5). If tremor persisted, conventional stereotactic thalamotomy with
      microrecording was performed. During such operations, normal neuronal activity
      was recorded from the region adjacent to the GKS thalamotomy target. This was the
      region showing a high signal on MR imaging. The activity patterns included the
      rhythmical grouped discharge of tremor rhythm. CONCLUSIONS: Gamma thalamotomy for
      functional disorders is still under development, but because the results with
      careful target planning are satisfactory, there are grounds for increasing
      optimism.

PMID- 12507105
TI  - Multimodal management of craniopharyngiomas: neuroendoscopy, microsurgery, and
      radiosurgery.
AB  - OBJECT: The goal of this study was to examine the role of gamma knife
      radiosurgery (GKS) and adjuvant neuroendoscopic procedures by assessing the
      outcome in 10 patients with craniopharyngiomas who were treated between 1998 and
      2001. METHODS: In 10 consecutive patients (six males and four females, mean age
      12 years [range 7-32 years]), there were nine mixed and one solid
      craniopharyngioma. In the last three cases, neuroendoscopic procedures were
      conducted. Two cases required insertion of an Ommaya reservoir. In another case
      partial removal of the cyst wall was performed using an endoscope to create a
      communication with the cerebrospinal pathways and thereby preclude the need for
      shunt insertion. CONCLUSIONS: Multimodal management of craniopharyngiomas seems
      to provide a better rate of survival and greater long-term disease control. It is
      suggested that GKS combined with adjuvant neuroendoscopy should be used as an
      alternative in treating recurrent or residual craniopharyngiomas if additional
      microsurgical removal cannot guarantee a cure.

PMID- 12507106
TI  - A planned combined stereotactic approach for cystic intracranial tumors. Report
      of two cases.
AB  - Cyst-associated tumors are classified as cysts with neoplastic mural nodules and
      intratumoral cysts. The solid component of many of these tumors may be
      appropriate for gamma knife radiosurgery (GKS). At present there is no systematic
      protocol for GKS treatment of patients harboring tumors with a cystic component.
      The purpose of this paper is to suggest such a program. Two cases are presented.
      One patient had a hemangioblastoma with a cyst and a mural nodule. The second
      patient had a craniopharyngioma with one large and two small intratumoral cysts.
      The course in both cases has been satisfactory in the short term. Although the 1
      year follow-up period, however, does not provide a basis for determining the
      correct overall management of such tumors, the treatment strategy does illustrate
      a program for the management of tumors with associated cysts. Cysts with tumor
      nodules in their walls should first be treated with GKS followed by aspiration of
      the cyst contents, unless special circumstances make this unsuitable. This
      strategy enables treatment planning to take advantage of the natural barrier a
      cyst may place between a tumor and important surrounding structures. Intratumoral
      cysts may be aspirated and then treated with GKS, with every attempt made to
      cover the entire target volume including any residual cyst with the prescription
      dose. This form of treatment requires very careful follow up. It is probable that
      in some cases reaccumulation of cyst fluid may require the insertion of an Ommaya
      reservoir for repeated aspiration or the installation of cytotoxic agents such as
      bleomycin. This form of treatment is much less traumatic than surgery and does
      not hinder the performance of subsequent surgery, should this become necessary.

PMID- 12507107
TI  - Gamma knife radiosurgery for craniopharyngiomas: long-term results in the first
      Swedish patients.
AB  - OBJECT: The purpose of this study was to assess the long-term treatment efficacy
      and morbidity of patients who undergo gamma knife radiosurgery (GKS) for
      craniopharyngioma. METHODS: Twenty-one consecutive Swedish patients were
      evaluated retrospectively: 11 children (< or = 15 years) and 10 adults. The time
      from diagnosis to the most recent follow-up imaging study was 6.3 to 34.3 years
      (mean 18.2 years, median 16.8 years). Tumor volumes and morbidity from GKS or
      other treatments were assessed at the time of the most recent imaging study or at
      the time of a subsequent new treatment. The observation period ranged from 0.5 to
      29 years (mean 7.5 years, median 3.5 years). The prescription dose ranged from
      less than 3 Gy to 25 Gy. The mean tumor volume was 7.8 cm3 (range 0.4-33 cm3).
      There were 22 tumors in 21 patients treated with GKS. Five of these tumors were
      reduced in size, three were unchanged, and 14 increased. Tumor progression
      correlated with a low dose to the tumor margin. Eleven (85%) of 13 tumors that
      received a dose of less than 6 Gy to the margin increased in size, whereas only
      three (33%) of nine tumors that received 6 Gy increased. This difference was
      statistically significant (p = 0.01). In five of six patients tumors that became
      smaller after GKS there were no recurrences within a mean follow-up period of 12
      years. Nine (82%) of 11 tumors in children ultimately increased after GKS,
      compared with five (50%) of 10 in adults. In eight patients there was a
      deterioration of visual function. In all except one this could be related to a
      volume increase but radiation-induced damage could not be excluded as a factor in
      any of them. Four patients developed pituitary deficiencies. CONCLUSIONS: Gamma
      knife radiosurgery is effective in controlling growth of craniopharyngiomas with
      a minimum dose of 6 Gy. The findings also suggest that other stereotactic
      techniques, such as cyst aspiration and intracystic treatment, are only of value
      in reducing tumor volume in preparation for safe GKS.

PMID- 12507108
TI  - Observations of intracranial neoplasms treated with gamma knife radiosurgery.
AB  - OBJECT: The purpose of this study was to compare histopathological changes with
      imaging findings in different tumors after gamma knife radiosurgery (GKS).
      METHODS: Five patients of a series of 220 treated with GKS underwent craniotomy
      for tumor removal 3 to 12 months after radiosurgery. There were two patients with
      multiple cerebral metastases, one with vestibular schwannoma, one with malignant
      glioma, and one with meningioma. A portion of normal brain tissue outside the
      prescription dose volume was acquired wherever possible to facilitate examination
      of the effects of radiosurgery. Histopathological and immunohistochemical
      investigations were performed. In addition to the routine hematoxylin and eosin
      and Mallory trichrome stains, immunohistochemical reactions were also performed
      for Factor VIII-associated antigen (FVIII) and CD34 antigen to study vascular
      endothelial effects of the irradiation. Endothelial cells of vessels in the
      normal brain tissue covering the tumor, outside of the prescription isodose
      volume, expressed marked CD34 and FVIII positivity. In the irradiated targeted
      tumor tissue samples, however, both reactions decreased remarkably. CONCLUSIONS:
      The results of the present immunohistochemical study provide support to the
      experimental hypothesis that vascular endothelial cells are the principal targets
      of single high-dose irradiation. The loss of central contrast enhancement of
      tumor tissue following radiosurgery might be consequence of the vascular damage.

PMID- 12507109
TI  - Morphological redifferentiation in a malignant astrocytic tumor after gamma knife
      radiosurgery.
AB  - OBJECT: The purpose of this study was to demonstrate positron emission tomography
      (PET), histological, and immunohistochemical data supporting the notion of
      morphological redifferentiation in a malignant astrocytic tumor after gamma knife
      radiosurgery (GKS). METHODS: The 11C- methionine-PET activity, Ki-67 labeling
      index (LI), and p53 protein expression were examined using immunohistochemical
      methods to assess tumor proliferative capacity. Tissue samples were obtained
      before and after radiosurgery in a patient with a malignant (Grade III)
      cerebellar astrocytoma. Positron emission tomography scans obtained 5.5 months
      following radiosurgery were suggestive of decreased tumor proliferative capacity
      and radionecrosis. Histological examination of tumor tissue removed 42 months
      before GKS was characteristic of a diffuse Grade III astrocytoma in every part of
      the resected tumor. Similar material removed 6 months after GKS was consistent
      with a Grade II astrocytoma in the great majority of the resected tumor.
      CONCLUSIONS: Histopathological examination showed positive phenotypic
      modification (redifferentiation) consistent with a Grade 11 astrocytoma in the
      majority of tumor specimens after radiosurgery. After GKS both the Ki-67 LI and
      p53 reaction decreased considerably as did 11C methionine uptake. Because p53 is
      one of the essential genes involved in the radiation response, mutations induced
      by the ionizing effect of gamma rays might promote partial repair of this gene's
      tumor suppressor function.

PMID- 12507110
TI  - Acute symptoms after gamma knife radiosurgery.
AB  - OBJECT: The purpose of this study was to examine the widely held assumption that
      early-onset symptoms after gamma knife radiosurgery (GKS) are uncommon. The study
      was designed to include all types of morbidity and not just those that lead to
      neurological dysfunction. It was hoped that the results of the study could lead
      to a more rational follow-up protocol. METHODS: Data regarding adverse events
      were collected prospectively (within 2-3 weeks post-GKS) by telephone interview
      from 47 of the first 65 patients who could be reached. Immediate adverse events
      were defined as any new or unexpected symptom developing within 2 weeks of
      treatment and were graded as mild, moderate, or severe. Two thirds of all
      patients complained of new adverse symptoms; three patients required prolonged
      hospitalization, although in one case this was not related to the radiosurgery.
      The majority of symptomatic patients (91%) experienced mild or moderate
      complications. More than 50% of patients had headache. One third described pin
      site-related complications and one fifth suffered from nausea/vomiting or marked
      tiredness. Patients with moderate symptoms had a larger mean tumor volume and
      higher radiation dose than other patient groups. Prior radiation therapy, lesion
      type, or the posttreatment administration of steroid agents did not significantly
      influence the development of acute symptoms. CONCLUSIONS: Acute adverse events
      following GKS are not uncommon if all types of morbidity are considered. An
      increased appreciation of these other complications may improve posttreatment
      care.

PMID- 12507111
TI  - Leksell gamma knife treatment of uveal melanoma.
AB  - OBJECT: The purpose of this study was to analyze treatment results, radiation
      induced side effects, and prognostic survival factors for patients with uveal
      melanoma. METHODS: Eighty-one patients with uveal melanoma were treated using the
      Leksell gamma knife during a period of 6 years (1996-2001). There were 45 men and
      36 women with a median age of 59 years (range 22-85 years). Seventy-five of these
      patients underwent minimal follow up 10 months after treatment. After patient eye
      immobilization, magnetic resonance (MR) imaging was performed to enable
      stereotactic localization. A scoring system was used to measure radiation side
      effects. The median target volume was 640 mm3, and the median applied minimal
      dose was 31.4 Gy. All patients were examined by an ophthalmologist and with MR
      imaging at regular intervals. Factors influencing posttreatment survival and side
      effects were statistically analyzed. CONCLUSIONS: Local tumor control in the 75
      patients who underwent minimal follow up after 10 months was achieved in 63
      patients (84%), whereas progression was observed in 12 patients (16%). The most
      frequent side effect was secondary glaucoma, which was detected in 18 patients
      (25%). The incidence of this side effect was significantly higher when the total
      volume of peripheral isodose was greater than 1000 mm3 (p = 0.015). Toxicity in
      the optic nerve here was also significantly higher when the maximum dose to this
      structure was higher than 9 Gy (p = 0.011), in the cornea when the maximum dose
      was higher than 15 Gy (p = 0.010), and in the lens when the maximum dose was
      higher than 10 Gy (p = 0.035). Altogether three pretreatment variables (patient
      age, tumor location, and dissemination of the disease) and one treatment variable
      (the minimum dose applied) were identified as having a significant influence on a
      patient's survival.

PMID- 12507112
TI  - High-compared with low-dose radiosurgery for uveal melanomas.
AB  - OBJECT: The authors compared the results of gamma knife radiosurgery in patients
      with uveal melanoma who underwent high-dose (treated from 1992-1995) and low-dose
      irradiation (treated from 1996-2002). METHODS: Thirty-one patients with uveal
      melanomas were treated with a mean margin dose of 52.1 Gy (high dose) and 33 with
      a mean dose of 41.5 Gy (low dose), and results were compared between groups. The
      technical procedure was the same in each group except for radiation dose. In the
      low-dose group, complete tumor regression (scar formation) occurred in 12% and in
      the high-dose group in 26%. Partial regression (reduction of the tumor prominence
      between 50 and 80%) occurred in 81% of the low-dose group and in 58% of the high
      dose group. Neovascular glaucoma as a severe complication developed in 9% of the
      low-dose group and in 48% of the high-dose group. CONCLUSIONS: Reduction of the
      margin dose from 52.1 to 41.5 Gy appears to achieve the same rate of tumor
      regression but is associated with a lower rate of severe side effects such as
      neovascular glaucoma. The follow-up period in the low-dose group, however, was
      much shorter.

PMID- 12507113
TI  - Gamma knife radiosurgery and its possible relationship to malignancy: a review.
AB  - The question has been raised recently whether gamma knife radiosurgery (GKS) can
      induce secondary neoplasia. Because there is little or no detailed knowledge
      about this potential complication, background information culled from the
      radiotherapy literature is reviewed as a guide to the clinical situations in
      which radiotherapy may induce secondary neoplastic change. Available case reports
      are then reviewed and discussed against the background of the current knowledge.
      On the basis of the review, the following suggestions are proposed on how to
      limiting the extent of this complication, document its frequency, and inform
      patients. It should be remembered that: the benefits of GKS are great; its
      alternatives also have risks; there often are no alternatives to GKS; follow-up
      documentation should be pursued more actively so that, if possible, no patient
      falls through the net; practitioners should be proactive in defining the problem,
      and genetic analysis of tumor biopsy specimens obtained in patients who will
      undergo or have undergone GKS should become routine; the extent of secondary
      neoplasia is not known; and patient information should be guided by what is known
      rather than by what is feared.

PMID- 12507114
TI  - Evaluation of gamma knife radiosurgery in the treatment of oligodendrogliomas and
      mixed oligodendroastrocytomas.
AB  - OBJECT: Radiosurgery is commonly used for the treatment of patients with glioma.
      The goal of this study was to evaluate the safety and efficacy of radiosurgery in
      the management of patients with oligodendrogliomas (ODGs) or mixed
      oligoastrocytomas (OGAs). METHODS: A retrospective chart review of patients
      treated between May 1990 and January 2000 identified 18 patients (21 tumors) with
      either an ODG (10) or a mixed OGA (11) who had undergone radiosurgery. The median
      patient age was 43 years (range 23-67 years). Sixteen patients had undergone one
      or more tumor resections before radiosurgery; in two patients biopsy sampling
      alone had been performed. Tumor grades at the most recent operation were Grade I
      (one), Grade 2 (one), Grade 3 (12), and Grade 4 (seven patients). Seventeen
      patients had undergone prior radiotherapy; 11 were treated with chemotherapy
      before radiosurgery, and one had undergone a prior linear accelerator-based
      radiosurgery treatment. The median tumor volume was 8.2 cm3 (range 1.9-47.7 cm3);
      the median margin dose was 15 Gy (range 12-20 Gy); and the median maximum dose
      was 32 Gy (range 24-50 Gy). In this heterogeneous group, 12 patients died whereas
      six remain alive. Survival after radiosurgery was 78%, 61%, and 44% at 12, 24,
      and 48 months, respectively. Factors associated with an improved survival rate
      included younger age and smaller tumors. CONCLUSIONS: For patients with
      oligoastroglial tumors that have failed to respond to conventional therapies,
      radiosurgery may provide some survival benefit. Further study is needed to
      determine which subpopulation of these patients will have the best chances of
      enhanced survival from this treatment.

PMID- 12507115
TI  - Intratumoral bleeding in meningioma after gamma knife radiosurgery.
AB  - OBJECT: The authors evaluated whether gamma knife radiosurgery (GKS) could be a
      causative factor in intratumoral bleeding in meningiomas. METHODS: Gamma knife
      radiosurgery was used in the treatment of 173 meningiomas during a 10-year
      period. Four patients suffered post-GKS intratumoral hemorrhage. The course in
      these patients was reviewed. Four of 173 patients suffered an intratumoral
      hemorrhage during a follow-up period of 1 to 8 years. The risk of intratumoral
      bleeding after GKS for meningioma was 2.3%. Intracystic hemorrhage occurred in
      two patients 1 and 5 years, respectively, after radiosurgery. In the other two
      cases intratumoral bleeding occurred 2 and 8 years, respectively, after
      radiosurgery. Histological examination in three cases found no specific findings
      related to the postradiosurgical changes. CONCLUSIONS: Because the reported risk
      of spontaneous intratumoral bleeding in meningiomas is 1.3 to 2.7%, the incidence
      in this series was not unduly high. Radiosurgery itself could not be shown to be
      a significant factor in the development of the intratumoral bleeding.

PMID- 12507116
TI  - Gamma knife radiosurgery in patients with advanced breast cancer undergoing bone
      marrow transplant.
AB  - OBJECT: Recent studies have suggested a high incidence of cognitive deficits in
      patients undergoing high-dose chemotherapy, which appears to be dose related.
      Whole-brain radiotherapy (WBRT) has previously been associated with cognitive
      impairment. The authors attempted to use gamma knife radiosurgery (GKS) to delay
      or avoid WBRT in patients with advanced breast cancer treated with high-dose
      chemotherapy and autologous bone marrow transplantation (HDC/ABMT) in whom brain
      metastases were diagnosed. METHODS: A retrospective review of our experience from
      1996 to 2001 was performed to identify patients who underwent HDC/ABMT for
      advanced breast cancer and brain metastasis. They were able to conduct GKS as
      initial management to avoid or delay WBRT in 12 patients following HDC/ABMT. All
      patients were women. The median age was 48 years (range 30-58 years). The
      Karnofsky Performance Scale score was 70 (range 60-90). All lesions were treated
      with a median prescription dose of 17 Gy (range 15-18 Gy) prescribed to the 50%
      isodose. Median survival was 11.5 months. Five patients (42%) had no evidence of
      central nervous system disease progression and no further treatment was given.
      Four patients were retreated with GKS and three of them eventually received WBRT
      as well. Two patients were treated with WBRT as the primary salvage therapy. The
      median time to retreatment with WBRT was 8 months after the initial GKS.
      CONCLUSIONS: Gamma knife radiosurgery can be effectively used for the initial
      management of brain metastases to avoid or delay WBRT in patients treated
      previously with HDC, with acceptable survival and preserved cognitive function.

PMID- 12507117
TI  - Leksell gamma knife lesioning of the rat hippocampus: the relationship between
      radiation dose and functional and structural damage.
AB  - OBJECT: The goals of the study were to determine at what dosage and after what
      interval impairment of hippocampal function occurs after Leksell gamma knife
      radiosurgery (GKS) of the rat hippocampus and to assess the associated structural
      changes. METHODS: Long-Evans rats were irradiated with maximum doses of 25, 50,
      75, 100, and 150 Gy, and four 4-mm isocenters were used to cover the hippocampus
      bilaterally. The impairment of hippocampal function, which is associated with a
      loss of memory, was measured by testing the impairment of the rats' orientation
      in a Morris water maze. Changes in the irradiated tissue were measured using
      magnetic resonance imaging (Bruker 4.7/20 experimental spectrometer). The data
      were compared with histologically demonstrated changes. Significantly higher
      incidences of edema, necrosis, and behavioral changes were observed following
      administration of doses higher than 50 Gy. No edema, necrosis, or behavioral
      changes were observed when doses were 25 Gy. CONCLUSIONS: It would seem that rats
      can be used for experiments involving the induction of complex brain lesions by
      using four 4-mm isocenters. Testing retention memory for behavioral changes after
      bilateral GKS of the whole hippocampus proved insensitive; acquisition memory
      should be tested to assess functional changes of hippocampus. Significantly
      higher incidences of edema, necrosis, and behavioral changes were observed for
      doses higher than 50 Gy. There seems to be a therapeutic window during which
      doses may affect epilepsy without impairing the memory of the rat.

PMID- 12507118
TI  - Skull base approaches and gamma knife radiosurgery for multimodality treatment of
      skull base tumors.
AB  - OBJECT: The purpose of this study was to evaluate descriptive data obtained in
      patients who had received multimodality treatment with resection and gamma knife
      radiosurgery (GKS) for skull base tumors. Retrospective data were collected from
      71 patients with skull base tumors who were treated from November 1996 to
      December 2000, all of whom underwent follow-up evaluation at 1 year or more.
      METHODS: Data were collected from hospital charts and office records, including
      patient age, tumor type and location, number of tumors, maximum radiation dose,
      estimated radiation dose to the periphery, tumor volume, and percentage of
      patients with tumors smaller or the same size at follow-up evaluation.
      CONCLUSIONS: Of the 71 patients with 1 year or more of follow up, 93% had tumor
      either the same size or smaller and 34% of these patients had a smaller tumor
      size. It is concluded that: 1) GKS with multimodality treatment is effective for
      control of skull base tumors; 2) the radiosurgical team should consider the
      benefits of GKS for treatment of any skull base tumor to afford optimum patient
      management; and 3) neurosurgeons involved with the management of skull base
      tumors should either be trained and proficient in GKS or work closely with a
      colleague trained in the technique. This will ensure proper consideration of both
      options, resulting in overall improved patient treatment.

PMID- 12507119
TI  - Gamma knife radiosurgery for pilocytic astrocytomas.
AB  - OBJECT: The authors report on the follow-up studies in patients treated at the
      Karolinska Hospital to evaluate the efficacy of gamma knife radiosurgery (GKS)
      for pilocytic astrocytoma. METHODS: Twelve male and seven female patients were
      treated (mean age 10.6 years [range 2-60 years]). Sixteen of these patients were
      children in whom GKS was performed to treat residual tumor after surgery. Most
      tumors were treated with a prescription dose of 10 to 12 Gy (range 9-20 Gy). The
      corresponding maximum dose varied between 22 and 30 Gy (range 10-50 Gy). The
      median clinical follow-up time was 7 years and mean clinical follow-up time 8.5
      years. Median radiological follow-up time was 4.7 years and the mean radiological
      follow-up time was 5.9 years. Tumor control was achieved in all patients. In 85%
      of the cases a moderate tumor volume reduction was observed after GKS. This
      result occurred despite the low prescription dose administered. The radiological
      follow-up studies showed adverse radiation effects in 25% of patients with
      increasing contrast enhancement and some edema. These effects generally appeared
      within 7 months and resolved later. Cyst development occurred in two patients,
      which may have been treatment related. CONCLUSIONS: It appears that small
      pilocytic astrocytomas may be treated with low-prescription-dose GKS, resulting
      in satisfactory clinical outcomes and only minor side effects. There were a
      certain number of radiologically demonstrated side effects that appeared
      relatively early but subsequently resolved. This study should be regarded as a
      preliminary one because the number of patients is small and the follow-up period
      is short compared with the natural time course of the disease.

PMID- 12507120
TI  - The voice of art and the art of medicine. The 2002 presidential address.
AB  - Vincent van Gogh's life, letters, and art are the framework for this existential
      speech about the nature of alienation, as well as its threat to humanity and to
      the artful practice of medicine. The honest, human voice expressed in van Gogh's
      art stands in opposition to alienation, which occurs when we divide the world
      into two parts: the "perfect" world of science versus the "flawed" world of human
      experience. Bridging this divide allows for an "authentic" life, one which
      honestly defines itself and faces difficult human truths. The most difficult
      truth relates to our own mortality, but it must be faced if we are to understand
      the value of existence. Film clips from Woody Allen's Hannah and Her Sisters
      illustrate how an artist's portrayal of these issues can be both profound and
      humorous, and how art brings us closer to our own humanity and to the essence of
      medicine. Neurosurgeons are warned about the lure of science and technology as a
      substitute for purpose and meaning, both as physicians and as human beings. The
      role of the American Association of Neurological Surgeons is explored and found
      to offer neurosurgeons a bridge away from alienation and toward a neurosurgical
      community. Neurosurgeons are urged to find meaning through service to their
      profession and to find the voice and art of medicine. [Note: Actual film clips
      were used when this address was delivered. Unofficial transcripts of the clips
      have been included in this article so that the integrity of the speech would not
      be compromised.]

PMID- 12507121
TI  - Cerebrospinal fluid production in patients with hydrocephalus.

PMID- 12507122
TI  - Downregulation of cerebrospinal fluid production in patients with chronic
      hydrocephalus.
AB  - OBJECT: The goal of this study was to determine the effect of hydrocephalus on
      cerebrospinal fluid (CSF) production rates in patients with acute and chronic
      hydrocephalus. METHODS: The authors studied CSF production both in patients
      presenting with acute and chronic hydrocephalus, and patients with Parkinson
      disease (PD) of a similar mean age, whose CSF production was known to be normal.
      A modification of the Masserman method was used to measure CSF production through
      a ventricular catheter. The CSF production rates (means +/- standard deviations)
      in the three groups were then compared. The patients with PD had a mean CSF
      production rate of 0.42 +/- 0.13 ml/minute; this value lies within the normal
      range measured using this technique. Patients with acute hydrocephalus had a
      similar CSF production rate of 0.4 +/- 0.13 ml/minute, whereas patients with
      chronic hydrocephalus had a significantly decreased mean CSF production rate of
      0.25 +/- 0.08 ml/minute. CONCLUSIONS: The authors postulate that chronic
      increased intracranial pressure causes downregulation of CSF production.

PMID- 12507123
TI  - Radiosurgery for non-small cell lung carcinoma metastatic to the brain: long-term
      outcomes and prognostic factors influencing patient survival time and local tumor
      control.
AB  - OBJECT: Lung carcinoma is the leading cause of death from cancer. More than 25%
      of those patients with lung cancer develop a brain metastasis at some time during
      the course of their disease. Corticosteroid therapy, radiotherapy, and resection
      have been the mainstays of treatment. Nonetheless, the median survival for
      patients with lung carcinoma metastasis is approximately 3 to 6 months. The
      authors examine the efficacy of gamma knife radiosurgery (GKS) for treating non
      small cell lung carcinoma (NSCLC) metastases to the brain and evaluate factors
      affecting long-term patient survival. METHODS: A retrospective review of 273
      patients who had undergone GKS to treat a total of 627 NSCLC metastases was
      performed. Clinical and neuroimaging data encompassing a 14-year treatment
      interval were collected. Univariate and multivariate analyses were performed to
      determine significant prognostic factors influencing patient survival. The
      overall median patient survival time was 15 months (range 1-116 months) from the
      diagnosis of brain metastases. The median survival was 10 months from GKS
      treatment in those patients with adenocarcinoma and 7 months for those with other
      histological tumor types. In patients with no active extracranial disease at the
      time of GKS, the median survival time was 16 months. In multivariate analyses,
      factors significantly affecting survival included: 1) female sex (p = 0.014); 2)
      preoperative Karnofsky Performance Scale score (p < 0.0001); 3) adenocarcinoma
      histological subtype (p = 0.0028); 4) active systemic disease (p = 0.0001); and
      5) time from lung cancer diagnosis to the development of brain metastasis (p =
      0.0074). Prior tumor resection or whole-brain radiation therapy did not correlate
      with extended patient survival time. Postradiosurgical imaging of brain
      metastases revealed that 60% decreased, 24% remained stable, and 16% eventually
      increased in size. Factors affecting local tumor control included tumor volume (p
      = 0.042) and treatment isodose (p = 0.015). Fourteen patients (5.1%) later
      underwent craniotomy and tumor resection for tumor refractory to GKS or a new
      symptomatic metastasis. CONCLUSIONS: Gamma knife surgery for NSCLC metastases
      affords effective local tumor control in approximately 84% of patients. Early
      detection of brain metastases, aggressive treatment of systemic disease, and a
      therapeutic strategy including GKS can afford patients an extended survival time.

PMID- 12507124
TI  - Reliability of the oral glucose tolerance test in the early postoperative
      assessment of acromegaly remission.
AB  - OBJECT: The suppression of growth hormone (GH) to less than 1 microg/L during the
      oral glucose tolerance test (OGTT) is generally considered to be the standard for
      the assessment of biochemical remission of GH excess following surgery for GH
      secreting pituitary adenomas. In this study the authors examine the reliability
      of the results of the early postoperative OGTT (epOGTT) in indicating remission
      or persistence of active acromegaly. METHODS: Data from the case files of 67
      consecutive patients who underwent surgery for the first time for GH-secreting
      pituitary adenomas were reviewed retrospectively. Definitive remission of
      acromegaly was considered to be present if, without adjuvant therapy and at the
      most recent follow-up examination, GH was suppressed to less than 1 microg/L
      during the OGTT, the level of insulin-like growth factor-I (IGF-I) was within
      normal limits, and there was no clinical or magnetic resonance imaging evidence
      of persisting disease. The results of the epOGTT (obtained during the 2nd
      postoperative week) and the 3-month-postoperative OGTT (3mpOGTT) were compared
      with the patient's outcome at the most recent follow-up examination. A highly
      sensitive (< or = 0.3 microg/L) immunoradiometric assay for GH and a highly
      sensitive (< or = 32 microg/L) radioimmunoassay for IGF-I were used. Correct
      epOGTT findings were noted in 83.6% of the patients: correct normal results
      (definitive remission of acromegaly) in 55.2% and correct pathological results
      (persisting acromegaly) in 28.3% of the patients. The rate of false findings was
      16.4%: false normal results in 1.5% and false pathological results in 14.9% of
      the patients. The rate of correct 3mpOGTT findings increased to 98.5%: correct
      normal results in 68.6% and correct pathological ones in 29.8% of the patients. A
      false (false pathological) 3pmOGTT result occurred in only one patient (1.5%). At
      the most recent follow-up examinations (median 3.6 years) all OGTT findings were
      correct: correct normal results in 70.1% and correct pathological results in
      29.9% of the patients. An intact adenopituitary function was associated (p =
      0.04) with the occurrence of false epOGTT findings. CONCLUSIONS: The high rate of
      false results, 16.4% for the epOGTT, declined significantly to 1.5% 3 months
      postoperatively and to 0% at the most recent follow-up examination. The OGTT
      appears to be more reliable at 3 months postoperatively. Unless there is obvious
      evidence of persisting disease following surgery for GH-secreting pituitary
      adenomas, adjuvant therapy should be delayed for 3 months postoperatively to
      avoid subjecting the patient to superfluous treatment.

PMID- 12507125
TI  - Plasma endothelin and big endothelin concentrations and serum endothelin
      converting enzyme activity following aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: Pathogenesis of delayed ischemia after aneurysmal subarachnoid hemorrhage
      (SAH) seems to be complex. An important mediator of chronic vasospasm may be
      endothelin (ET)-1 with its powerful and long-lasting vasoconstricting activity.
      In this prospective study the author investigated the correlations between serial
      plasma concentrations of ET-1 and big ET-1 as well as the ET-1/big ET-1 molar
      concentration ratio and serum endothelin-converting enzyme (ECE)-1 activity, and
      ischemic complications after SAH. METHODS: To measure plasma ET-1 (51 patients),
      big ET-1 immunoreactivity (22 patients), and serum ECE-1 activity (13 patients),
      blood samples were obtained on admission, in the morning after aneurysm surgery,
      and during the 2nd week after hemorrhage in 51 consecutive patients (28 men and
      23 women, with a mean age of 50.8 years) with aneurysmal SAH. Mean plasma
      concentrations of ET-1 in patients with SAH (mean +/- standard deviation: on
      admission, 4.2 +/- 2 pg/ml; after surgery, 4.3 +/- 2.2 pg/ml; and during the 2nd
      week after SAH, 3.7 +/- 1.9 pg/ml) differed from those in healthy volunteers (2.9
      +/- 1.2 pg/ml; p < 0.01). Plasma concentrations of ET-1 and big ET-1 as well as
      the ET-1/big ET-1 ratio did not change significantly with elapsed time following
      SAH; however, serum ECE-1 activity during the 2nd week after SAH was higher in
      patients with SAH than that in controls (162 +/- 43 compared with 121 +/- 56
      pg/ml, respectively; p = 0.028). Plasma ET-1 concentrations (p < 0.05) and the ET
      1/big ET-1 ratios (p = 0.063) were higher but plasma big ET-1 concentrations were
      lower (p < 0.05) in patients who experienced symptomatic delayed cerebral
      ischemia, compared with other patients with SAH. In addition, in cases in which
      follow-up computerized tomography scans or magnetic resonance images demonstrated
      permanent ischemic lesions attributable to vasospasm, patients had higher ET-1
      concentrations than did other patients with SAH. CONCLUSIONS: The plasma ET-1
      concentration correlates with delayed cerebral ischemia after SAH, suggesting
      that an increased ET conversion rate in the endothelium predicts ischemic
      symptoms. Increased serum ECE-1 activity during the 2nd week may reflect the
      severity of endothelial injury to cerebral arteries.

PMID- 12507126
TI  - Staged stent-assisted angioplasty for symptomatic intracranial vertebrobasilar
      artery stenosis.
AB  - OBJECT: Medically refractory symptomatic vertebrobasilar atherosclerotic disease
      has a poor prognosis. Studies have shown that longer (> or = 10 mm), eccentric,
      high-grade (> 70%) stenoses portend increased procedure-related morbidity. The
      authors reviewed their experience to determine whether a staged procedure
      consisting of angioplasty followed by delayed (> or = 1 month later) repeated
      angioplasty and stent placement reduces the morbidity associated with
      endovascular treatment of symptomatic basilar and/or intracranial vertebral
      artery (VA) stenoses. METHODS: The authors retrospectively reviewed the medical
      records in a consecutive series of eight patients who underwent planned stent
      assisted angioplasty for medically refractory, symptomatic atherosclerotic
      disease of the intracranial posterior circulation between February 1999 and
      January 2002. Staged stent-assisted angioplasty was planned for these patients
      because the extent and degree of stenosis of the VA and/or basilar artery (BA)
      lesion portended an excessive procedure-related risk. The degree of stenosis,
      recent onset of symptoms (unstable plaque), vessel tortuosity, and lesion length
      and morphological feaures were contributing factors in determining procedure
      related risk. Patient records were analyzed for location and degree of stenosis,
      preprocedural regimen of antiplatelet and/or anticoagulation agents, devices
      used, procedure-related complications, and clinical and radiographic outcomes.
      Among the patients in whom staged stent-assisted angioplasty was planned, vessel
      dissection, which necessitated immediate stent placement, occurred during passage
      of the balloon in one of them. In a second patient, the stent could not be
      maneuvered through the tortuous VA. In a third patient, the VA and BAs remained
      widely patent after angioplasty alone, and therefore stent placement was not
      required. Significant complications among the eight patients included transient
      aphasia and hemiparesis in one and a groin hematoma that necessitated surgical
      intervention in another; there was no permanent neurological morbidity. The mean
      stenosis before treatment was 78%, which fell to 54% after angioplasty, and the
      mean residual stenosis after stent placement was 30%. At the last follow-up
      examination, none of the treated patients had further symptoms attributable to
      the treated stenosis. CONCLUSIONS: The novel combination of initial angioplasty
      followed by delayed endoluminal stent placement may reduce the neurological
      morbidity associated with endovascular treatment of long, high-grade stenotic
      lesions. Attempting to cross high-grade stenoses with higher-profile devices such
      as stents may result in an embolic shower. Furthermore, neointimal proliferation
      and scar formation after angioplasty result in a thickened fibrous layer, which
      may be protective during delayed stent deployment. Larger-scale studies involving
      multiple centers are needed to elucidate further the lesion morphological
      characteristics and patient population most likely to benefit from staged
      procedures.

PMID- 12507127
TI  - Increased levels of lipid peroxides as predictive of symptomatic vasospasm and
      poor outcome after aneurysmal subarachnoid hemorrhage.
AB  - OBJECT: Cerebral vasospasm remains a devastating medical complication of
      aneurysmal subarachnoid hemorrhage (SAH). Reactive oxygen species and subsequent
      lipid peroxidation are reported to participate in the causes of cerebral
      vasospasm. This clinical study was performed to investigate the relationships
      between levels of lipid peroxides in cerebrospinal fluid (CSF) and both delayed
      cerebral vasospasm and clinical outcome after SAH. METHODS: Levels of
      phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide
      (CEOOH) in the CSF were measured in 20 patients with aneurysmal SAH. The
      patients' CSF was collected within 48 hours of hemorrhage onset and on Day 6 or 7
      post-SAH. On Day 7, angiography was performed to verify the degree and extent of
      the vasospasm. The relationship between the patients' clinical profiles and the
      levels of lipid peroxides in the CSF were investigated. Both PCOOH and CEOOH were
      detectable in CSF, and their levels decreased within 7 days after onset of SAH.
      The levels of CEOOH within 48 hours after onset of hemorrhage were significantly
      higher in patients in whom symptomatic vasospasm later developed than in patients
      in whom symptomatic vasospasm did not develop (p = 0.002). Levels of PCOOH
      measured within 48 hours after onset of hemorrhage were significantly higher in
      patients with poor outcomes than in patients with good outcomes (p = 0.043).
      CONCLUSIONS: Increased levels of lipid peroxides measured in the CSF during the
      acute stage of SAH were predictive of both symptomatic vasospasm and poor
      outcome. Measurements of lipid peroxides in the CSF may be useful prognostically
      for patient outcomes as well as for predicting symptomatic vasospasm.

PMID- 12507128
TI  - Endovascular reconstruction of intracranial arteries by stent placement and
      combined techniques.
AB  - OBJECT: The authors investigated the feasibility, safety, and short-term outcome
      of stent treatment for intracranial aneurysms, stenoses, and dissections.
      METHODS: One hundred twenty-three consecutive patients with intracranial
      saccular, dissecting, and fusiform aneurysms, atherosclerotic lesions, and
      dissections were selected for intracranial stent implantation with or without
      adjunctive coil placement. One hundred eleven patients (mean age 47 years, range
      3-73 years) underwent stent treatment; 12 patients (9.8%) were not treated. These
      111 patients were divided into four groups: in Group 1 there were 62 patients
      with saccular aneurysms; Group 2 included nine patients (10 lesions) with
      dissecting or fusiform aneurysms; in Group 3 there were 36 patients with
      symptomatic intracranial atheromatous stenoses of more than 50%; and Group 4
      included four patients with symptomatic intracranial dissections. All patients
      underwent computerized tomography scanning and/or magnetic resonance imaging and
      cerebral digital subtraction angiography preoperatively. Of the 72 aneurysms in
      Groups 1 and 2, 59 (82%) were treated with combined endovascular stent
      implantation and endosaccular coil placement. In 67 aneurysms (93%) we achieved
      complete or nearly complete obliteration. All patients with arterial narrowing
      achieved residual stenoses of less than 30% postangioplasty. One patient required
      repeated angioplasty. The morbidity rate in the series was 10.9% and the
      mortality rate was 6.3%. CONCLUSIONS: These findings indicate that stent
      treatment is feasible and seems to be an effective modality for arterial
      reconstruction. This versatile tool allows the treatment of a wide variety of
      challenging intracranial lesions.

PMID- 12507129
TI  - Cerebral hemodynamics and metabolism in patients with cerebral arteriovenous
      malformations: an evaluation using positron emission tomography scanning.
AB  - OBJECT: The purpose of this study was to evaluate cerebral hemodynamic and
      metabolic features in patients with arteriovenous malformations (AVMs) by using
      positron emission tomography (PET) scanning. METHODS: Twenty-four patients with
      supratentorial cerebral AVMs participated in PET studies in which 15O inhalation
      steady-state methods were used. The authors recorded the values of regional
      cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), the regional
      oxygen extraction fraction (rOEF), and the regional cerebral metabolic rate of O2
      (rCMRO2) at three designated regions of interest (ROIs) in each patient. These
      ROIs included perilesional (ROI-p), ipsilateral remote (ROI-i), and contralateral
      symmetrical (ROI-c) brain regions. To identify the factors that exert a direct
      effect on the hemodynamics of brains affected by AVM, we also separated the
      lesions according to their size and flow type shown on angiograms, and grouped
      the patients according to the presence or absence of progressive neurological
      deficits. We then compared the PET parameters at different ROIs in individual
      patients and evaluated the mean values obtained for all 24 patients according to
      AVM flow type and size, and the presence or absence of progressive neurological
      deficits. CONCLUSIONS: Overall, mean rCBV and rOEF values were significantly
      higher in ROI-p than in ROI-c (p = 0.00046 and p = 0.015, respectively). No
      significant differences were seen between the ROI-i and ROI-c with respect to
      rCBF, rCBV, and rOEF. Mean rCMRO2 values were similar in the three ROIs; however,
      the mean rCBF was significantly lower in the ROI-p than in the ROI-c in patients
      with high-flow AVMs (p = 0.019), large AVMs (p = 0.017), and progressive
      neurological deficits (p = 0.021). Furthermore, the mean rOEF values were
      significantly higher in the ROI-p than in the ROI-c in patients with high-flow
      AVMs (p = 0.005), large AVMs (p = 0.019), and progressive neurological deficits
      (p = 0.017). The PET studies revealed hemodynamic impairment characterized by
      decreased rCBF and increased rOEF and rCBV values in the ROI-p of patients with
      large, high-flow AVMs regardless of whether they exhibited progressive
      neurological deficits.

PMID- 12507130
TI  - Three-dimensional helical computerized tomography angiography in the diagnosis,
      characterization, and management of middle cerebral artery aneurysms: comparison
      with conventional angiography and intraoperative findings.
AB  - OBJECT: Middle cerebral artery (MCA) aneurysms can be difficult to detect and
      characterize. The authors describe the utility and impact of helical computerized
      tomography (CT) angiography for the evaluation of aneurysms in this location, and
      compare this modality with digital subtraction (DS) angiography and
      intraoperative findings. METHODS: Two hundred fifty-one patients with suspected
      cerebral aneurysms underwent CT angiography. Two-dimensional multiplanar
      reformatted images and three-dimensional CT angiograms were examined by two
      independent readers in a blinded fashion. Results were compared with findings on
      DS angiograms to determine the relative efficacy of these modalities in the
      detection and characterization of aneurysms. Questionnaires completed by
      neurosurgeons and endovascular therapists were used to determine the impact of CT
      angiograms on aneurysm management. Twenty-eight patients harboring 31 MCA
      aneurysms and 26 patients without aneurysms were identified using CT angiography.
      The sensitivity of CT angiography and DS angiography for MCA aneurysms was 97%;
      both techniques showed 100% specificity. In 76% of evaluations, the CT
      angiography studies provided information not available on DS angiography
      examinations. For the characterization of aneurysms, CT angiography was rated
      superior (72%) or equal (20%) to DS angiography in 92% of cases evaluated (p <
      0.001). Computerized tomography angiography was evaluated as the only study
      needed for patient triage in 82% of cases (p < 0.001), and as the only study
      needed for treatment planning in 89% of surgically treated (p < 0.001) and in 63%
      of endovascularly treated cases (p < 0.001). The information acquired on CT
      angiograms changed the initial treatment plan in 24 (67%) of these 36 complex
      lesions (p < 0.01). The aneurysm appearance intraoperatively was identical or
      nearly identical to that seen on CT angiograms in 17 (89%) of 19 of the
      surgically treated cases. CONCLUSIONS: Computerized tomography angiography has
      unique advantages over DS angiography and is a viable alternative to the latter
      modality in the diagnosis, triage, and treatment planning in patients with MCA
      aneurysms.

PMID- 12507131
TI  - Preoperative magnetic source imaging for brain tumor surgery: a quantitative
      comparison with intraoperative sensory and motor mapping.
AB  - OBJECT: The aim of this study was to compare quantitatively the methods of
      preoperative magnetic source (MS) imaging and intraoperative electrophysiological
      cortical mapping (ECM) in the localization of sensorimotor cortex in patients
      with intraaxial brain tumors. METHODS: Preoperative magnetoencephalography (MEG)
      was performed while patients received painless tactile somatosensory stimulation
      of the lip, hand, and foot. The early somatosensory evoked field was modeled
      using a single equivalent current dipole approach to estimate the spatial source
      of the response. Three-dimensional magnetic resonance image volume data sets with
      fiducials were coregistered with the MEG recordings to form the MS image. These
      individualized functional brain maps were integrated into a neuronavigation
      system. Intraoperative mapping of somatosensory and/or motor cortex was performed
      and sites were compared. In two subgroups of patients we compared intraoperative
      somatosensory and motor stimulation sites with MS imaging-based somatosensory
      localizations. Mediolateral projection of the MS imaging source localizations to
      the cortical surface reduced systematic intermodality discrepancies. The distance
      between two corresponding points determined using MS imaging and ECM was 12.5 +/-
      1.3 mm for somatosensory-somatosensory and 19 +/- 1.3 mm for somatosensory-motor
      comparisons. The observed 6.5 mm increase in site separation was systematically
      demonstrated in the anteroposterior direction, as expected from actual anatomy.
      In fact, intraoperative sites at which stimulation evoked the same patient
      response exhibited a spatial variation of 10.7 +/- 0.7 mm. CONCLUSIONS:
      Preoperative MS imaging and intraoperative ECM show a favorable degree of
      quantitative correlation. Thus, MS imaging can be considered a valuable and
      accurate planning adjunct in the treatment of patients with intraaxial brain
      tumors.

PMID- 12507132
TI  - Basis of persistent and recurrent Cushing disease: an analysis of findings at
      repeated pituitary surgery.
AB  - OBJECT: The goal of this study was to establish the clinical importance of occult
      dural invasion--invasion of the dura mater or cavernous sinus that is not evident
      on imaging studies and is not obvious to the surgeon--as the basis of recurrent
      or persistent tumor and endocrinopathy. METHODS: The authors retrospectively
      reviewed the case files of patients who underwent repeated transsphenoidal
      surgery for resection of an adrenocorticotropic hormone (ACTH)-producing
      pituitary adenoma. Patient selection required the availability of operative and
      pathology reports from the initial and repeated transsphenoidal surgeries.
      Because no determination of the cause of persistent or recurrent disease could be
      made if the tumor could not be localized during the repeated surgery, a pathology
      report confirming the presence of tumor from the second surgery was also
      required. Sixty-eight patients met these criteria. In 43 patients (63%) an ACTH
      producing tumor was identified at the initial surgery, in 25 patients (37%) no
      tumor was found, and in three patients (4%) dural invasion was noted at surgery.
      In 49 (72%) of the 68 patients there was initial resolution of hypercortisolism
      and recurrent Cushing disease (CD), whereas in 19 patients (28%) there was
      persistent CD after the initial surgery. At repeated surgery (44 +/- 35 months
      after the initial surgery) in all 43 patients in whom tumor had been identified
      at the initial surgery, the tumor was found at the same site or contiguous to the
      same site. Dural invasion was noted by the surgeon in only three patients at the
      original surgery, whereas dural invasion by an ACTH-producing tumor was
      identified during repeated surgery in 42 (62%) of the 68 patients. In addition,
      39 (93%) of the 42 invasive adenomas were located laterally and involved the
      cavernous sinus. Adenomatous invasion of the dura mater was found in 31 (54%) of
      the 57 microadenomas and in all 11 macroadenomas at repeated surgery. The
      presence of tumor was not detected in 28 of the 59 patients studied with magnetic
      resonance (MR) imaging and in none of these 59 patients was dural invasion
      evident on MR images. CONCLUSIONS: Recurrent and persistent CD consistently
      results from residual tumor. At repeated surgery the residual tumor can be found
      at or immediately contiguous to the site at which the tumor was found originally.
      Unappreciated dural invasion with growth of residual tumor within the cavernous
      sinus dura, which frequently occurs without residual tumor or dural invasion
      being evident on MR images or to the surgeon during surgery, is the basis of
      surgical failure in many patients with CD. Occult lateral dural invasion by tumor
      may also underlie recurrences of other types of pituitary adenomas.

PMID- 12507133
TI  - Genetic differences between neurocytoma and dysembryoplastic neuroepithelial
      tumor and oligodendroglial tumors.
AB  - OBJECT: Because of their histological similarities, it is occasionally difficult
      to differentiate neurocytoma and dysembryoplastic neuroepithelial tumor (DNT)
      from oligodendroglial tumors. This study was conducted to investigate genetic
      differences among these tumor types in terms of loss of heterozygosity on
      chromosomes 1p and 19q, and p53 gene mutation. METHODS: A total of 24 tumors were
      analyzed, consisting of eight central neurocytomas, three DNTs, seven
      oligodendrogliomas, four oligoastrocytomas, and two undetermined extraventricular
      tumors with neurocytoma features (ETNFs). Allelic loss was determined using
      microsatellite markers that cover the common deletions on chromosomes 1p and 19q
      in oligodendrogliomas. A p53 gene mutation was identified using polymerase chain
      reaction-single-strand conformation polymorphism analysis and subsequent direct
      sequencing. Immunohistochemical studies with synaptophysin and electron
      microscopy investigations were also conducted. Allelic loss on 1p and 19q was
      detected in six oligodendrogliomas (86%) and in three oligoastrocytomas (75%),
      but in none of the central neurocytomas or DNTs. A p53 missense mutation was
      detected at codon 161 (GCC-->ACC, Ala-->Thr) in only one oligoastrocytoma without
      allelic loss. Synaptophysin was expressed in all central neurocytomas and DNTs,
      in three oligodendrogliomas (43%), and in three oligoastrocytomas (75%). Of the
      ETNFs, one demonstrated synaptophysin expression and neural ultrastructures but
      lacked genetic alterations, whereas the other showed allelic loss on 1p and 19q
      but was negative immunohistochemically and ultrastructurally. The former was
      diagnosed as a potential intraparenchymal neurocytoma and the latter as an
      oligodendroglioma. CONCLUSIONS: Despite histological similarities, central
      neurocytomas and DNTs are genetically distinct from oligodendroglial tumors.
      Examination for allelic loss on 1p and 19q and for p53 mutation can be useful for
      making this distinction.

PMID- 12507134
TI  - Complex tumors of the glomus jugulare: criteria, treatment, and outcome.
AB  - OBJECT: Tumors of the glomus jugulare are benign, slow-growing paragangliomas.
      Their natural history, surgical treatment, and outcome have been well addressed
      in the recent literature; however, there remains a subgroup of complex tumors-
      multiple, giant, malignant, neuropeptide-secreting lesions, and those treated
      previously by an intervention with an adverse outcome--that is high risk,
      presents surgical challenges, and is associated with treatment controversy. In
      this article the authors report on a series of patients with complex glomus
      jugulare tumors and focus on treatment decisions, avoidance of complications,
      surgical refinements, and patient outcomes. METHODS: In this retrospective study,
      the patient population was composed of 11 male and 32 female patients (mean age
      47 years) with complex tumors of the glomus jugulare who were treated by the
      senior author within the past 20 years. These include 38 patients with giant
      tumors, 11 with multiple paragangliomas (seven bilateral and four ipsilateral),
      two with tumors that hypersecreted catecholamine, and one with a malignant tumor.
      Six patients had associated lesions: one dural arteriovenous malformation, one
      carotid artery (CA) aneurysm, two adrenal tumors, and two other cranial tumors.
      All but one patient presented with neurological deficits. Cranial nerve deficits,
      particularly those associated with the lower cranial nerves, were the prominent
      feature. Twenty-eight patients underwent resection in an attempt at total
      removal, and gross-total resection was achieved in 24 patients. Particularly
      challenging were cases in which the patient had undergone prior embolization or
      CA occlusion, after which new feeding vessels from the internal CA and
      vertebrobasilar artery circulation developed. The surgical technique was tailored
      to each patient and each tumor. It was modified to preserve facial nerve
      function, particularly in patients with bilateral tumors. Intrabulbar dissection
      was performed to increase the likelihood that the lower cranial nerves would be
      preserved. Each tumor was isolated to improve its resectability and prevent blood
      loss. No operative mortality occurred. In one patient hemiplegia developed
      postoperatively due to CA thrombosis, but the patient recovered after an
      endovascular injection of urokinase. In four patients a cerebrospinal fluid leak
      was treated through spinal drainage, and in five patients infection developed in
      the external ear canal. Two of these infections progressed to osteomyelitis of
      the temporal bone. There were two recurrences, one in a patient with a malignant
      tumor who eventually died of the disease. CONCLUSIONS: Despite the challenges
      encountered in treating complex glomus jugulare tumors, resection is indicated
      and successful. Multiple tumors mandate a treatment plan that addresses the risk
      of bilateral cranial nerve deficits. The intrabulbar dissection technique can be
      used with any tumor, as long as the tumor itself has not penetrated the wall of
      the jugular bulb or infiltrated the cranial nerves. Tumors that hypersecrete
      catecholamine require perioperative management and malignant tumors carry a poor
      prognosis.

PMID- 12507135
TI  - New laboratory model for neurosurgical training that simulates live surgery.
AB  - OBJECT: Laboratory training models are essential for developing and refining
      surgical skills, especially for microsurgery. The closer to live surgery the
      model is, the greater the benefit. In this paper the authors introduce a cadaver
      model with unique characteristics: dynamic filling of the cerebral vasculature
      with colored liquid and clear fluid filling of the arachnoid cisterns. This model
      is distinctive and has great practical value for training in a wide range of
      surgical procedures. METHODS: Cadaveric heads were prepared for surgical
      procedures in the following manner: the carotid arteries (CAs) and vertebral
      arteries (VAs) in the neck were cannulated, as were the internal jugular veins
      (JVs) on both sides. Two tubes were introduced into the spinal canal and each one
      was advanced into one of the cerebellopontine angle cisterns. A CA, VA, or both
      were then connected to a reservoir containing light red fluid and a pressure of
      80 to 120 mm Hg and a pulse rate of 60 beats/minute were established using a
      pump. The JV on the side currently being dissected was connected to a reservoir
      containing dark red fluid and kept at a pressure between 20 and 40 mm Hg. The
      remaining vessels were clamped in the neck. The cisternal tubes were connected to
      a reservoir of clear fluid that was regulated by an adjustable flow. Nine
      trainees have tested this model on eight specimens by practicing a variety of
      surgical procedures and maneuvers, including craniotomies; hemostasis; cisternal
      and vascular dissection; vascular anastomosis and repair; establishment of
      arterial bypasses; aneurysm creation, dissection, and clipping; management of an
      aneurysm rupture; intraparenchymal resection such as amygdalohippocampectomy;
      ventricular endoscopy and third ventriculostomy; cavernous sinus and skull base
      approaches; and resection of artificial tumors in the basal cisterns.
      CONCLUSIONS: This model mimics the normal human anatomy and dynamic vascular
      filling found in real surgery and presents it from the training perspective,
      allowing a wide range of skill development and repeated practice. It provides an
      alternative model to laboratory animals. It is inexpensive and readily available,
      and has great value for the acquisition and refinement of surgical skills that
      are not only specific to neurosurgery, but are applicable to other surgical
      disciplines.

PMID- 12507136
TI  - Intravascular coagulation: a major secondary insult in nonfatal traumatic brain
      injury.
AB  - OBJECT: The goal of this study was to determine the frequency with which cerebral
      intravascular coagulation (IC) complicates traumatic brain injury (TBI). The
      authors also investigated the incidence of IC in relation to varying mechanisms,
      time courses, and severities of TBI and in different species. METHODS: Tissue was
      sampled from surgical specimens of human cerebral contusions, from rats with
      lateral fluid-percussion injuries, and from pigs with head rotational
      acceleration injuries. Immunohistochemical fluorescent staining for antithrombin
      III was performed to detect cerebral intravascular microthrombi. Abundant IC was
      found in all specimens, and microthrombi had formed in arterioles and venules of
      all sizes, ranging from 10 to 600 microm. Although it was more pronounced in
      focal lesions and more severe injuries, considerable IC was also observed in mild
      and diffuse injuries. The authors found a strong association between the severity
      of coagulopathy and the density of IC. CONCLUSIONS: These results strongly
      support the contention that IC is a universal response to TBI and an important
      secondary cerebral insult.

PMID- 12507137
TI  - Induction of glioblastoma multiforme in nonhuman primates after therapeutic doses
      of fractionated whole-brain radiation therapy.
AB  - OBJECT: To determine the acute and long-term effects of a therapeutic dose of
      brain radiation in a primate model, the authors studied the clinical, laboratory,
      neuroimaging, molecular, and histological outcomes in rhesus monkeys that had
      received fractionated whole-brain radiation therapy (WBRT). METHODS: Twelve 3
      year-old male primates (Macaca mulatta) underwent fractionated WBRT (350 cGy for
      5 days/week for 2 weeks, total dose 3500 cGy). Animals were followed clinically
      and with laboratory studies and serial magnetic resonance (MR) imaging. They were
      killed when they developed medical problems or neurological symptoms, lesions
      appeared on MR imaging, or at study completion. Gross, histological, and
      molecular analyses were then performed. Nine (82%) of 11 animals that underwent
      long-term follow up (> 2.5 years) developed neurological symptoms and/or
      enhancing lesions on MR imaging, which were defined as glioblastoma multiforme
      (GBM), 2.9 to 8.3 years after radiation therapy. The GBMs were categorized as
      either unifocal (three) or multifocal (six), and were located in the
      supratentorial (six), infratentorial (two), or both (one) cranial regions.
      Histological examination revealed distant, noncontiguous tumor invasion within
      the white matter of all nine animals harboring GBMs. Novel interspecies
      comparative genomic hybridization (three animals) uniformly showed deletions in
      the GBMs that corresponded to chromosome 9 in humans. CONCLUSIONS: The high rate
      of GBM formation (82%) following a therapeutic dose of WBRT in nonhuman primates
      indicates that radioinduction of these neoplasms as a late complication of this
      therapy may occur more frequently than is currently recognized in human patients.
      The development of these tumors while monitoring the monkeys' conditions with
      clinical and serial MR imaging studies, and access to the tumor and the entire
      brain for histological and molecular analyses offers an opportunity to gather
      unique insights into the nature and development of GBMs.

PMID- 12507138
TI  - Analysis of immunoglobulin H gene rearrangement by polymerase chain reaction in
      primary central nervous system lymphoma.
AB  - OBJECT: Diagnosing primary central nervous system lymphoma (PCNSL) may be
      difficult either because of a paucity of tumor cells in the brain biopsy
      specimens or a failure to demonstrate monoclonality on immunomorphological
      studies. Monoclonality can also be demonstrated by amplification of the
      rearranged immunoglobulin H genes by polymerase chain reaction (PCR) to the
      framework region (FR)3 and FR2 complementarity determining region (CDR)-III and
      CDR-II of these genes. The PCR method is feasible with formalin-fixed, paraffin
      embedded biopsy material and has proven to be helpful in the diagnosis of non
      Hodgkin lymphoma on biopsy samples obtained from various locations in the body.
      Nevertheless, few studies have addressed the value of this method in the context
      of PCNSL. In the present study, the contribution of both FR3 single and FR2
      seminested PCR procedures for confirming the diagnosis of PCNSL was estimated
      retrospectively in 30 cases of PCNSL and in three cases of epidural lymphoma.
      METHODS: Twenty-eight cases of immunophenotypically confirmed PCNSL and two of
      suspected lymphoma were studied. Tissue specimens obtained in 22 cases of other
      cerebral diseases, among which were various inflammatory conditions. were used as
      negative controls. In 18 (60%) of 30 cases the results of FR3 PCR demonstrated
      monoclonality, whereas FR2 PCR showed monoclonality in 12 cases (40%). In 11
      cases FR3 PCR yielded monoclonal patterns and FR2 PCR did not, whereas reversibly
      in five cases FR2 PCR proved monoclonality and FR3 PCR failed to do so. Adding
      the results of FR3 to those of FR2 PCR, monoclonal patterns were obtained in 23
      (77%) of 30 cases. In both cases in which lymphoma was suspected but not proven
      immunomorphologically, FR3 PCR revealed monoclonality, as did FR2 PCR in one
      case. In all 22 control lesions either polyclonal patterns were seen or no
      consistent patterns were obtained. In the PCNSL group, older age of patients and
      multifocal presentation of lesions on neuroimaging were significantly associated
      with worse survival. No correlation between histological subtype and clinical
      outcome was elucidated. CONCLUSIONS: The application of FR3 and FR2 PCR is a
      useful additional tool in making the diagnosis of PCNSL. Moreover, in some cases
      the PCR method may be essential in distinguishing neoplasia from reactive
      conditions.

PMID- 12507139
TI  - Analysis of loss of chromosome 10q, DMBT1 homozygous deletions, and PTEN
      mutations in oligodendrogliomas.
AB  - OBJECT: Chromosomal deletions of 10q and candidate genes such as PTEN and DMBT1
      have been thoroughly investigated in glioblastomas but few data specifically
      address oligodendrogliomas. METHODS: In this study, 39 pure oligodendrogliomas
      were investigated for loss of heterozygosity (LOH) on 10q, PTEN mutations, and
      DMBT1 homozygous deletions. The LOH on 10q was found in 19 (48%) of 39
      oligodendrogliomas and was closely related to anaplasia (p = 0.02), shorter time
      to progression (p = 0.0005), and poorer survival (p = 0.035). The DMBT1
      homozygous deletions were found in 10 (26%) of 39 oligodendrogliomas but only one
      PTEN mutation was detected. The LOH on 10q is a strong predictor of survival and
      could be a valuable prognostic marker in oligodendrogliomas. CONCLUSIONS:
      Frequent inactivation of DMBT1 contrasting with rare mutations of PTEN may
      indicate that DMBT1 is preferentially involved in oligodendrogliomas.
      Nevertheless, the absence of a correlation with survival makes the role of DMBT1
      in tumorigenesis still questionable and warrants further investigation.

PMID- 12507140
TI  - Clinical and electrophysiological expression of deafferentation pain alleviated
      by dorsal root entry zone lesions in rats.
AB  - OBJECT: The aims of this study were to construct an animal model of
      deafferentation of the spinal cord by brachial plexus avulsion and to analyze the
      effects of subsequent dorsal root entry zone (DREZ) lesions in this model. To
      this end, the authors measured the clinical and electrophysiological effects of
      total deafferentation of the cervical dorsal horn in rats and evaluated the
      clinical efficacy of cervical DREZ lesioning. METHODS: Forty-three Sprague-Dawley
      rats were subjected to total deafferentation of the right cervical dorsal horn by
      performing a posterior rhizotomy from C-5 to T-1. The clinical effects of this
      deafferentation, namely self-directed mutilations consisting of scraping and/or
      ulceration of the forelimb skin or even autotomy of some forelimb digits, were
      then evaluated. As soon as some of these clinical signs of pain appeared, the
      authors performed a microsurgical DREZ rhizotomy ([MDR], microincision along the
      deafferented DREZ and dorsal horn). Before and after MDR, single-unit recordings
      were obtained in the deafferented dorsal horn and in the contralateral (healthy)
      side. The mean frequency of spontaneous discharge from the deafferented dorsal
      horn neurons was significantly higher than that from the healthy side (36.4 Hz
      compared with 17.9 Hz, p = 0.03). After deafferentation, 81.4% of the rats
      developed clinical signs corresponding to pain following posterior rhizotomy.
      Among these animals, scraping was observed in 85.7% of cases, ulceration
      (associated with edema) in 37.1%, and autotomy in 8.5%. These signs appeared a
      mean 5.7 weeks (range 1-12 weeks) after deafferentation. Thirteen rats benefited
      from an MDR; nine (69%) experienced a complete cure, that is, a total resolution
      of scraping or ulceration (a mean 4.6 weeks after MDR). In contrast, only one of
      11 sham-operated animals showed signs of spontaneous recovery (p = 0.01).
      CONCLUSIONS: These results emphasize the role of the spinal dorsal horn in the
      genesis of deafferentation pain and suggest that dorsal horn deafferentation by
      cervical posterior rhizotomy in the rat provides a reliable model of chronic pain
      due to brachial plexus avulsion and its suppression by MDR.

PMID- 12507141
TI  - A new reproducible model of an epidural mass lesion in rodents. Part I:
      Characterization by neurophysiological monitoring, magnetic resonance imaging,
      and histopathological analysis.
AB  - OBJECT: The goal of this study was to characterize a new model of an epidural
      mass lesion in rodents by means of neurophysiological monitoring, magnetic
      resonance imaging, and histopathological analysis. METHODS: Changes in
      intracranial pressure (ICP), cerebral perfusion pressure (CPP), and laser Doppler
      flowmetry (LDF) values, intraparenchymal tissue partial oxygen pressure (PtiO2),
      and electroencephalography (EEG) activity were evaluated in the rat during
      controlled, epidural expansion of a latex balloon up to a maximum ICP of 60 mm
      Hg. The initial balloon inflation was followed by periods of sustained inflation
      (30 +/- 1 minute) and reperfusion (180 +/- 5 minutes). Histopathological analysis
      and magnetic resonance (MR) imaging were performed to characterize the lesion.
      The time to maximum balloon expansion and the average balloon volume were highly
      reproducible. Alterations in EEG activity during inflation first appeared when
      the CPP decreased to 57 mm Hg, the LDF value to 66% of baseline values. and the
      PtiO2 to 12 mm Hg. During maximum compression, the CPP was reduced to 34 mm Hg,
      the LDF value to 40% of baseline, and the PtiO2 to 4 to 5 mm Hg. The EEG tracing
      was isoelectric during prolonged inflation and the values of LDF and PtiO2
      decreased due to accompanying hypotonia. After reperfusion, the CPP was
      significantly decreased (p < 0.05) due to the elevation of ICP. Both the LDF
      value and EEG activity displayed incomplete restoration, whereas the value of
      PtiO2 returned to normal. Histological analysis and MR imaging revealed brain
      swelling with a midline shift and a combined cortical-subcortical ischemic lesion
      beyond the site of balloon compression. CONCLUSIONS: This novel model of an
      epidural mass lesion in rodents closely resembles the process observed in humans.
      Evaluation of pathophysiological and morphological changes was feasible by using
      neurophysiological monitoring and MR imaging.

PMID- 12507142
TI  - A reproducible model of an epidural mass lesion in rodents. Part II:
      Characterization by in vivo magnetic resonance imaging.
AB  - OBJECT: The goal of this study was to characterize a novel epidural space
      occupying lesion caused by balloon expansion in rodents by using sequential in
      vivo magnetic resonance (MR) imaging. METHODS: Ten Sprague-Dawley rats were
      intraperitoneally sedated. A trephination was performed over the left parietal
      cortex to attach a balloon-expansion device, which was secured with dental
      cement. Measurements were performed using a 1.5-tesla MR imaging device to obtain
      sequential T2-weighted and diffusion-weighted (DW) sequences in the coronal
      plane. A three-dimensional, constructed interference in steady state sequence was
      used for calculation of the balloon volume. The animal's temperature, heartbeat,
      and the arterial percentage of oxygen saturation were monitored continuously.
      After a baseline examination had been performed, the balloon was inflated for a
      30-minute period until it reached a maximum volume of 0.3 ml; this procedure was
      followed by a period of sustained inflation lasting 30 minutes, balloon
      deflation, and a period of reperfusion lasting 3 hours. After perfusion fixation
      of the animals, morphometric analysis of the lesion size and examination of the
      percentage of viable neurons in the hippocampus were performed. Magnetic
      resonance imaging allowed for the precise visualization of the extension and
      location of the epidural mass lesion, narrowing of the basal cisterns, and
      development of a midline shift. A white-matter focus of hyperintensity,
      consistent with brain edema, developed, predominantly in the contralateral
      temporal lobe. During sustained inflation the volume of the balloon did not
      change and comprised 5 to 7% of total intracranial volume. During the same period
      the white-matter edema progressed further but no increased signal was revealed on
      DW images. After balloon deflation the brain reexpanded to the calvaria and
      imaging signs of raised intracranial pressure subsided. A cortical area of
      hyperintensity on T2-weighted images developed in the parietal lobe in the region
      of the former balloon compression. This area appeared bright on DW images, a
      finding that corresponded to an early cytotoxic edema. After deflation white
      matter vasogenic edema in the temporal lobes regressed within 3 hours after
      reperfusion. The cortical edema in the parietal lobe and the ipsilateral basal
      ganglia became sharply demarcated. The histopathological results (that is, the
      extent of tissue damage) corresponded with findings of the authors' companion
      investigation, which appears in this issue. CONCLUSIONS: Magnetic resonance
      imaging allows for a precise and sequential in vivo monitoring of a space
      occupying epidural mass lesion and visualizes the time course of vasogenic and
      cytotoxic brain edema. This rodent model of an epidural mass lesion proved to be
      reproducible.

PMID- 12507143
TI  - Painful neuromas: a potential role for a structural transmembrane protein,
      ankyrin G.
AB  - OBJECT: Severe nerve injury induces the formation of a neuroma. Some neuromas
      cause excruciating pain. Overexpression of Na+ channels leads to
      hyperexcitability and painful phenomena. Ankyrin G, a multifunctional
      transmembrane protein of the axolemma, might be a key protein in neuroma
      formation because it binds Na+ channels in the initial segments of a regenerating
      axon and links with neuronal cell adhesion molecules. The authors wanted to
      determine if ankyrin G could be detected in neuroma, and if present, whether
      there would be differences in distribution between nonpainful neuromas, painful
      neuromas, and normal nerve. METHODS: First, frozen sections of nine nerve
      specimens obtained from six patients (six nonpainful neuromas, one painful
      neuroma, and two normal nerves) were immunocytochemically screened for ankyrin G
      by using confocal laser scanning microscopy. Second, specimens from 29 patients
      (seven painful neuromas, 15 nonpainful neuromas, and seven normal nerves) were
      examined using immunoblot analysis for their ankyrin G content. Western blot
      analysis detected ankyrin G, which was visualized by applying the enhanced
      chemiluminescence technique. Computerized densitometry was used to quantitate
      ankyrin G expression by comparing band intensities. Normal nerve served as
      control. Neurofilament was used as a marker for nerve tissue content. Ankyrin G
      could be detected and was found to be increased in neuromas. The mean band
      intensity values were 1838 for painful neuromas, 1166 for nonpainful neuromas,
      and 411 for normal nerves. In two cases the authors were able to compare
      specimens of painful neuroma and normal nerve from the same patient. The painful
      neuromas exhibited considerably higher levels of ankyrin G. Painful neuroma and
      normal nerve densitometry values were 499 and 165, respectively, for one patient,
      and 4254 and 821, respectively, for the other patient. Painful neuromas were also
      found to have higher neurofilament values than nonpainful neuromas. CONCLUSIONS:
      Altered regulation of ankyrin G after nerve injury may lead to hyperexcitability
      and painful phenomena via clustering of Na+ channels. A propensity to overexpress
      ankyrin G after peripheral nerve trauma may turn out to be a factor in the
      development of painful neuromas and neuropathic pain. The relevant literature
      regarding the importance of ankyrin G for nerve regeneration and nerve membrane
      remodeling is reviewed.

PMID- 12507144
TI  - Treatment of an anterior communicating artery aneurysm through an anomalous
      anastomosis from the cavernous internal carotid artery.
AB  - Cavernous internal carotid artery (ICA)-anterior cerebral artery (ACA)
      anastomoses are unusual anomalies in which a duplicated A, segment of the ACA
      arises from the infraoptic ICA. The authors report on a 30-year-old woman who
      presented with subarachnoid hemorrhage from an anterior communicating artery
      (ACoA) aneurysm associated with an extremely rare variant of this anastomosis.
      The extra A, segment emerged from the ICA within the cavernous sinus rather than
      at or above the level of the ophthalmic artery. The presence of the anomalous
      vessel provided a straightforward endovascular approach to the ACoA and allowed
      the use of coil placement rather than surgical clipping to treat the aneurysm
      successfully.

PMID- 12507145
TI  - Rapid development of an intranidal aneurysm with perifocal brain edema in an
      unruptured cerebral arteriovenous malformation. Case report.
AB  - The authors present the case of a 22-year-old man with an unruptured
      arteriovenous malformation (AVM) in which an intranidal aneurysm had grown in the
      course of 3 months and was complicated by perifocal brain edema. A left parietal
      AVM was incidentally diagnosed on magnetic resonance (MR) imaging. No aneurysms
      were noted on cerebral angiograms obtained simultaneously. Three months later, T2
      weighted MR imaging revealed perifocal brain edema (increased signal intensity in
      the brain parenchyma adjacent to the nidus). An aneurysm-like signal void was
      demonstrated in the center of the high-signal area, but no previous hemorrhages
      could be detected. Angiographic studies revealed an intranidal aneurysm 4 mm in
      diameter projecting anterolaterally from the nidus. Surgical removal was
      performed without incident, and no neurological deficits or postoperative
      complications were observed. An MR image obtained 2 weeks postsurgery revealed
      complete resolution of the perifocal brain edema. To the authors' knowledge, this
      is the first reported case of an unruptured AVM in which an intranidal aneurysm
      with perifocal brain edema developed rapidly (within a few months).

PMID- 12507146
TI  - Hajdu-Cheney syndrome and syringomyelia. Case report.
AB  - This 7-year-old boy with Hajdu-Cheney syndrome presented with cervical
      syringomyelia related to rapidly progressing platybasia. Decompressive
      craniectomy provided temporary improvement, and his clinical status was
      eventually stabilized after external immobilization, according to findings at 2.5
      years of follow up. In a review of the literature the authors found 57 cases of
      the syndrome, only three of which were associated with syringomyelia. The youth
      of the patient, the severe form and rapid course of the disease, and the very
      specific anatomical conditions related to cranial and facial deformities raised
      various therapeutic problems.

PMID- 12507147
TI  - Decompressive aspiration in myelinoclastic diffuse sclerosis or Schilder disease.
      Case report.
AB  - This 9-year-old girl with rapidly progressive cerebral demyelinating disease
      presented with hemiplegia and intracranial hypertension. Brain images revealed
      four lesions with mass effect in the subcortical white matter of both
      hemispheres. Demyelination was found on pathological studies of these lesions.
      The patient experienced some recovery with corticosteroid treatment but improved
      completely with decompressive aspiration of the largest lesion.

PMID- 12507148
TI  - Malignant rhabdoid meningioma arising in the setting of preexisting
      ganglioglioma: a diagnosis supported by fluorescence in situ hybridization. Case
      report.
AB  - A highly malignant brain neoplasm with rhabdoid morphological features emerged in
      the bed of a subtotally resected ganglioglioma in a 54-year-old retired nuclear
      submarine officer. A combined application of neuroimaging, immunohistochemical
      studies, electron microscopy, and fluorescence in situ hybridization (FISH) was
      used to establish the morphological identity of the tumor. The rhabdoid
      appearance of the tumor cells indicated either an especially malignant variant of
      rhabdoid meningioma or an atypical teratoid/rhabdoid tumor with an unusually late
      onset. Whereas immunohistochemical studies and electron microscopy could only be
      used to narrow down the differential diagnosis, FISH revealed loss of one copy of
      NF2 with preservation of the INI1 region on 22q, thus establishing the identity
      of the tumor.

PMID- 12507149
TI  - Rotational vertebral artery occlusion from occipital bone anomaly: a rare cause
      of embolic stroke. Case report.
AB  - Vertebral artery (VA) occlusion by rotation of the head is uncommon, but can
      result from mechanical compression of the artery, trauma, or atlantoaxial
      instability. Occipital bone anomalies rarely cause rotational VA occlusion, and
      patients with nontraumatic intermittent occlusion of the VA usually present with
      compromised vertebrobasilar flow. A 34-year-old man suffered three embolic
      strokes in the vertebrobasilar system within 2 months. Magnetic resonance imaging
      demonstrated multiple infarcts in the vertebrobasilar territory. Angiography
      performed immediately after the third attack displayed an embolus in the right
      posterior cerebral artery. Radiographic and three-dimensional computerized
      tomography bone images exhibited an anomalous osseous process of the occipital
      bone projecting to the posterior arch of the atlas. Dynamic angiography indicated
      complete occlusion of the left VA between the osseous process and the posterior
      arch while the patient's head was turned to the right. Surgical decompression of
      the VA resulted in complete resolution of rotational occlusion of the artery. An
      occipital bone anomaly can cause rotational VA occlusion at the craniovertebral
      junction in patients who present with repeated embolic strokes resulting from
      injury to the arterial wall.

PMID- 12507150
TI  - Vision of the future: initial experience with intraoperative real-time high
      resolution dynamic infrared imaging. Technical note.
AB  - High-resolution dynamic infrared (DIR) imaging provides intraoperative real-time
      physiological, anatomical, and pathological information; however, DIR imaging has
      rarely been used in neurosurgical patients. The authors report on their initial
      experience with intraoperative DIR imaging in 30 such patients. A novel, long
      wave (8-10 microm), narrow-band, focal-plane-array infrared photodetector was
      incorporated into a camera system with a temperature resolution of 0.006 degrees
      C, providing 65,000 pixels/frame at a data acquisition rate of 200 frames/second.
      Intraoperative imaging of patients was performed before and after surgery.
      Infrared data were subsequently analyzed by examining absolute differences in
      cortical temperatures, changes in temperature over time, and infrared intensities
      at varying physiological frequencies. Dynamic infrared imaging was applied in a
      variety of neurosurgical cases. After resection of an arteriovenous malformation,
      there was postoperative hyperperfusion of the surrounding brain parenchyma, which
      was consistent with a loss of autoregulation. Bypass patency and increased
      perfusion of adjacent brain were documented during two of three extracranial
      intracranial bypasses. In seven of nine patients with epilepsy the results of DIR
      imaging corresponded to seizure foci that had been electrocorticographically
      mapped preoperatively. Dynamic infrared imaging demonstrated the functional
      cortex in four of nine patients undergoing awake resection and cortical
      stimulation. Finally, DIR imaging exhibited the distinct thermal footprints of 14
      of 16 brain tumors. Dynamic infrared imaging may prove to be a powerful
      adjunctive intraoperative diagnostic tool in the neurosurgical imaging
      armamentarium. Real-time assessment of cerebral vessel patency and cerebral
      perfusion are the most direct applications of this technology. Uses of this
      imaging modality in the localization of epileptic foci, identification of
      functional cortex during awake craniotomy, and determination of tumor border and
      intraoperative brain shift are avenues of inquiry that require further
      investigation.

PMID- 12507151
TI  - Quantification of susceptibility artifacts produced on high-field magnetic
      resonance images by various biomaterials used for neurosurgical implants.
      Technical note.
AB  - Although various biomaterials such as ceramics or titanium alloy are widely used
      in neurosurgery, the susceptibility artifacts that appear around these materials
      cause problems when a magnetic resonance (MR) imager is used to assess lesions
      after surgery. The purpose of the present study was to quantify the
      susceptibility artifacts produced by various biomaterials used for neurosurgical
      implants. Using a 3-tesla MR imaging unit, we obtained MR images of various
      biomaterials, including six types of ceramics, a cobalt-based alloy (Elgiloy),
      pure titanium, a titanium alloy, and stainless steel. All implants shared a
      uniform size and shape. In each image, a linear region of interest was defined
      across the center of the biomaterial in the transverse direction, and the
      diameter of the susceptibility artifact was calculated. The ceramics produced a
      considerably smaller artifact diameter than those produced by other biomaterials.
      Among the types of ceramics, zirconia was found to produce the smallest artifact
      diameter. Among the remaining biomaterials, the diameters of the artifacts
      decreased in order from that associated with stainless steel to those associated
      with cobalt-based alloys, pure titanium, and titanium alloy. Little difference
      was observed between the artifact diameters associated with pure titanium and
      titanium alloy. Ceramics are the most suitable biomaterials for minimizing
      artifacts in high-field MR imaging.

PMID- 12507152
TI  - Implantation of deep brain stimulation electrodes in unshaved patients. Technical
      note.
AB  - Although hair removal prior to neurosurgery may increase the risk of infection,
      the practice of shaving the patient's entire head is still common, particularly
      in implant surgery. The authors describe a technique for implanting a deep brain
      stimulation electrode without shaving the patient's hair and present a
      retrospective analysis of 261 implantations in 221 cases.

PMID- 12507153
TI  - An anterior ethmoidal artery aneurysm associated with an olfactory groove
      meningioma. Case illustration.

PMID- 12507154
TI  - Paracinoid aneurysms.

PMID- 12507155
TI  - Repeated computerized tomography scans.

PMID- 12507156
TI  - Dural arteriovenous fistulas.

PMID- 12507157
TI  - Genetic counseling in preconception health care.

PMID- 12507158
TI  - Assessment of lactose tests.

PMID- 12507159
TI  - The mammography debate.

PMID- 12507160
TI  - The mattress sutures: vertical, horizontal, and corner stitch.
AB  - The interrupted vertical and horizontal mattress suture techniques are two of the
      most commonly used skin closure methods. These mattress sutures promote wound
      edge eversion and less prominent scarring. Vertical and horizontal mattress
      sutures allow for skin edges to be closed under tension when wound edges have to
      be brought together over a distance. The corner stitch, a variation of the
      horizontal mattress suture, is commonly used for closure of angled skin flaps or
      wounds. Although mattress sutures can produce surface scarring or "railroad
      marks," early removal of these sutures can limit this damage.

PMID- 12507161
TI  - Overview of histoplasmosis.
AB  - Histoplasmosis is an endemic infection in most of the United States and can be
      found worldwide. The spectrum of this illness ranges from asymptomatic infection
      to severe disseminated disease. Life-threatening illness is usually associated
      with an immunocompromised state; however, 20 percent of severe illnesses result
      from a heavy inoculum in healthy persons. Culture remains the gold standard for
      diagnosis but requires a lengthy incubation period. Fungal staining produces
      quicker results than culture but is less sensitive. Testing for antigen and
      antibodies is rapid and sensitive when used for particular disease presentations.
      An advantage of antigen detection is its usefulness in monitoring disease
      therapy. Antifungal therapy is indicated in chronic or disseminated disease and
      severe, acute infection. Amphotericin B is the agent of choice in severe cases;
      however, patients must be monitored for nephrotoxicity and hypokalemia.
      Itraconazole is effective in moderate disease and is well tolerated, even with
      long-term use. Hepatotoxicity, the most severe adverse effect of itraconazole, is
      uncommon and usually transient.

PMID- 12507162
TI  - Information from your family doctor. What is histoplasmosis? How is it treated?

PMID- 12507163
TI  - Gluten-sensitive enteropathy (celiac disease): more common than you think.
AB  - Gluten-sensitive enteropathy or, as it is more commonly called, celiac disease,
      is an autoimmune inflammatory disease of the small intestine that is precipitated
      by the ingestion of gluten, a component of wheat protein, in genetically
      susceptible persons. Exclusion of dietary gluten results in healing of the
      mucosa, resolution of the malabsorptive state, and reversal of most, if not all,
      effects of celiac disease. Recent studies in the United States suggest that the
      prevalence of celiac disease is approximately one case per 250 persons. Gluten
      sensitive enteropathy commonly manifests as "silent" celiac disease (i.e.,
      minimal or no symptoms). Serologic tests for antibodies against endomysium,
      transglutaminase, and gliadin identify most patients with the disease. Serologic
      testing should be considered in patients who are at increased genetic risk for
      gluten-sensitive enteropathy (i.e., family history of celiac disease or personal
      history of type I diabetes) and in patients who have chronic diarrhea,
      unexplained anemia, chronic fatigue, or unexplained weight loss. Early diagnosis
      and management are important to forestall serious consequences of malabsorption,
      such as osteoporosis and anemia.

PMID- 12507164
TI  - Information from your family doctor. Celiac disease.

PMID- 12507165
TI  - Breast-conserving surgery for breast cancer.
AB  - Surgical treatment of breast cancer has changed significantly in recent years.
      Fine-needle aspirations or core-needle biopsies can be used in the diagnostic
      process, thus avoiding scarring incisions. The preferred method of treatment for
      many women with early breast cancer is conservative surgical therapy (principally
      lumpectomy and axillary dissection) followed by breast irradiation. Sentinel node
      biopsy is being investigated as an alternative to standard axillary node
      dissection. This could decrease morbidity following standard axillary dissection.
      These techniques allow women with different forms of breast cancer to conserve
      their breasts. For women who choose mastectomy, immediate reconstruction of the
      breast is now routinely performed with a prosthetic implant or autologous tissue.
      Clinical history, physical examination, and breast imaging are the most effective
      means of follow-up.

PMID- 12507166
TI  - Information from your family doctor. Breast-conserving surgery.

PMID- 12507167
TI  - Screening for breast cancer.

PMID- 12507168
TI  - Screening for colorectal cancer: recommendation and rationale.

PMID- 12507169
TI  - The 2003 Recommended Adult Immunization Schedule. Advisory Committee on
      Immunization Practices. American Academy of Family Physicians. American College
      of Obstetricians and Gynecologists. American College of Physicians. American
      Society of Internal Medicine. Centers for Disease Control and Prevention.

PMID- 12507170
TI  - Immunological abnormalities in humans chronically exposed to chlorpyrifos.
AB  - Twenty-nine individuals with chronic health complaints following exposure to
      chlorpyrifos were compared with 3 control groups (i.e., 1 positive and 2
      negative) with respect to the following: (1) peripheral lymphocyte phenotypes;
      (2) autoantibodies (nucleic acids and nucleoproteins, parietal cell, brush
      border, mitochondria, smooth muscle, thyroid gland, and central nervous
      system/peripheral nervous system myelin); (3) mitogenesis to phytohemagglutinin
      and concanavillin. The data revealed an increase in CD26 expression, a decrease
      in percentage of CD5 phenotype, decreased mitogenesis in response to
      phytohemagglutinin and concanavillin, and an increased frequency of
      autoantibodies. The alterations in these peripheral blood markers were unaffected
      by medications, age, sex, or season. The authors concluded that chronic exposure
      to chlorpyrifos causes immunological changes.

PMID- 12507171
TI  - Allergic susceptibility associated with diesel exhaust particle exposure: clear
      as mud.
AB  - Exposure to elevated levels of particulate air pollution from motor vehicles is
      frequently associated with increased morbidity and mortality from cardiovascular
      conditions, lung cancer, and nonmalignant respiratory illnesses (e.g., asthma,
      bronchitis, respiratory tract infections). It appears, however, that less
      attention has been paid to the potential role of road traffic fumes in the
      induction of allergic conditions. Laboratory studies in humans and animals have
      shown that particulate toxic pollutants-particularly diesel exhaust particulates
      can enhance allergic inflammation and can induce allergic immune responses. Most
      of these immune responses are mediated by the carbon core of diesel exhaust
      particulates. Polyaromatic hydrocarbons (e.g., anthracene, fluoranthene, pyrene,
      phenanthrene) are major chemical components of diesel exhaust particulates, and
      they have enhanced the production of immunoglobulin E. Although several large
      epidemiological studies have demonstrated a strong association between exposure
      to motor vehicle traffic emissions and allergic symptoms and reduced lung
      function, the evidence for the development of allergic sensitization from diesel
      exhaust particulates is less abundant than for the aforementioned associations.
      Recent comparisons of the prevalence of hay fever, as well as positive skin-prick
      tests, between citizens of former West and East Germany and between Hong Kong and
      China civilians, have demonstrated marked differences. Crucial variations in the
      level of particulate air pollution from motor vehicles in these countries may
      account for the observed increased prevalence of atopy. Although road-traffic
      pollution from automobile exhausts may be a risk factor for atopic sensitization,
      the evidence in support of this view remains conflictive. Some investigators have
      reported a clear association between the prevalence of allergy and road-traffic
      related air pollution, whereas such a difference was not observed in other
      studies. Most discrepancies have been related to important variations in study
      design and methodology. In addition, inasmuch as exposure to ambient particles
      differs substantially in worldwide urban environments, perhaps qualitative-rather
      than quantitative-variations in particulate air pollution at different locations
      account for differences in the prevalence and/or severity of respiratory
      allergies.

PMID- 12507172
TI  - Respiratory effects of air pollutants among asthmatics in central Taiwan.
AB  - The authors investigated the relationship between respiratory effects and air
      pollutants among asthmatics in central Taiwan. A total of 12,926 subjects were
      selected from 8 junior high schools. Data about monthly hospital admissions for
      respiratory illnesses were collected over a period of 1 yr from the National
      Insurance Bureau. Data included how frequently subjects purchased medication and
      the respiratory symptoms recorded by clinic and hospital personnel. Pulmonary
      function tests were administered to 20% of the total study population, which was
      selected randomly. Data about monthly levels of air pollutants (i.e., particulate
      matter 10 pm and less [PM10], ozone [O3], sulfur dioxide [SO2], and nitrogen
      dioxide [NO2]) were provided by Taiwan's Environmental Protection Agency. The
      prevalence rates of asthma were correlated significantly with NO2 (r = .63) and
      03 (r = .51) concentrations. Levels of NO2 and PM10 were correlated significantly
      with monthly hospital admissions. Forced vital capacity, forced expiratory volume
      in 1 sec, and peak expiratory flow for asthmatics in central Taiwan were 6-11%
      lower than normal predicted values for the general Taiwanese student population,
      adjusted for age, height, and weight. In conclusion, the increased risk of asthma
      and the frequency of monthly hospital admissions among asthmatics may be
      correlated positively with pollution levels-especially NO2 and PM10. air
      pollutants, asthma, mon

PMID- 12507173
TI  - Childhood cancer incidence and arsenic exposure in drinking water in Nevada.
AB  - Inorganic arsenic exposure through drinking water causes cancer in adults;
      however, the carcinogenic potential in children remains unknown. A recent
      leukemia cluster in Churchill County, Nevada, where arsenic levels in water
      supplies are relatively high, has prompted concern. The authors investigated the
      incidence of childhood cancer between 1979 and 1999 in all 17 Nevada counties,
      grouped by low (i.e., < 10 microg/l), medium (10-25 microg/l), and high (35-90
      microg/l) population-weighted arsenic levels in public drinking water supplies.
      The standardized incidence ratios (SIRs) for all childhood cancers combined were
      1.00 (95% confidence interval [CI] = 0.94, 1.06), 0.72 (95% CI = 0.43, 1.12), and
      1.25 (95% CI = 0.91, 1.69) for low-, medium-, and high-exposure counties,
      respectively. There was no relationship between arsenic levels in water and
      childhood leukemia (SIRs = 1.02, 0.61, and 0.86, respectively [95% CIIs = 0.90,
      1.15; 0.12, 1.79; and 0.37, 1.70, respectively]). For all childhood cancers,
      excluding leukemias, the SIRs were 0.99 (95% CI = 0.92, 1.07), 0.82 (95% CI =
      0.42, 1.22), and 1.37 (0.92, 1.83), respectively. The excess in 5- to 9-yr-old
      children and 10- to 14-yr-old children was in bone cancers, and the excess in 15-
      to 19-yr-old young adults was primarily in lymphomas. The findings in this study
      are reassuring in that leukemia risks were not increased at the concentrations of
      arsenic in water found in this study. Nonetheless, the results raise the
      possibility that there are increased risks for nonleukemic childhood cancers that
      require confirmation in other studies, particularly those in which higher
      exposures are addressed.

PMID- 12507174
TI  - An automated exposure system for human inhalation study.
AB  - The authors developed a computer-based exposure system for human inhalation
      research to study the toxicokinetics of gases. The system uses a set of computer
      controlled solenoid valves that regulates inhaled gases and collect exhaled
      breaths from the subject in accordance with a predetermined time schedule. The
      volunteer's breathing activity is monitored simultaneously with a real-time
      instrument, calibrated by both internal and external standards. The common air
      pollutant, 1,3-butadiene, was used for system validation. The results indicated
      that the errors were less than 3% relative to reference standards, and the error
      in the timing of the valve operation was negligible. The average difference
      between breath-monitoring methods was within 10%. The proposed system is an easy
      to-use, reliable device for human studies; more than 130 subjects were tested in
      a companion study.

PMID- 12507175
TI  - Lack of sensitivity of urinary trans,trans-muconic acid in determining low-level
      (ppb) benzene exposure in children.
AB  - Benzene is a widespread pollutant of which the main source in the outside
      environment is automotive traffic. Benzene is also present in cigarette smoke,
      and small quantities exist in drinking water and food; all of these sources
      contribute to pollution of indoor environments. Benzene exposure may be studied
      with biologic indicators. In the present study, the authors evaluated whether
      differences in urinary concentrations of trans,transmuconic acid (t,t-MA) were
      detectable in a sample of 150 children and if the chemical was correlated with
      environmental exposures to low levels of benzene. The children attended primary
      schools that had significantly different-but low-environmental benzene levels.
      Analysis of urinary t,t-MA was achieved with high-performance liquid
      chromatography (photodiode array detector), and analysis of passive air samplers
      for benzene was performed with gas chromatography-mass spectrometry. Statistical
      analysis (Kruskal-Wallis test) indicated that differences in urinary levels of
      t,t-MA in children from urban and rural areas were not statistically significant
      (p = .07), nor were there significant differences between children with and
      without relatives who smoked (p = .69). As has been shown in other studies of
      children and adults, results of our study evidenced (1) the difficulty of
      correlating concentrations of urinary biomarkers with environmental exposure to
      benzene at a parts-per-billion level (i.e., traffic and environmental tobacco
      smoke) and, consequently, (2) the lack of specificity of t,t-MA as a biological
      indicator for the study of a population's exposure.

PMID- 12507176
TI  - Medicinal herbs: a potential source of toxic metal exposure for man and animals
      in India.
AB  - To explore the possibility of translocation of heavy metals into humans and
      animals, the authors studied 28 commonly used medicinal plants and estimated
      their heavy metal content. The plant materials were collected from the same
      sources used by traditional healers and commercial drug manufacturers. The plants
      were identified, authenticated, and processed for the analysis of toxic metals.
      Lead and cadmium levels were estimated in leaf, stem bark, root, or seeds,
      depending on the medicinal value of the plant portion. The authors used an atomic
      absorption spectrophotometer to determine levels of metals. The mean lead
      concentration in medical herbs ranged between 2.624 ppm (standard deviation =
      0.426) and 32.757 (standard deviation = 0.124 ppm), and the cadmium concentration
      ranged between 0.056 ppm (standard deviation = 0.002) and 0.419 ppm (standard
      deviation = 0.006). Interestingly, the heavy metal concentrations (i.e., lead and
      cadmium) were higher in leaf than in stem bark or roots, and the lowest values
      were recorded in seeds. No published reports on the permissible level of toxic
      metals in commonly used medicinal plants of India have come to the authors'
      attention; therefore, it was difficult for the authors to determine the role of
      toxic metals in drug-induced health hazards. However, the presence of toxic
      metals in different plants led to the conclusion that prolonged consumption of
      such medicinal plants may be detrimental to health.

PMID- 12507177
TI  - Toluene at environmentally relevant low levels disrupts differentiation of
      astrocyte precursor cells.
AB  - Recent findings that describe endocrine disruption caused by exposure to low
      levels of certain chemicals in the environment have led to a paradigm shift in
      the way toxicology studies are designed. Toluene at high levels damages the human
      central nervous system; however, the effects of toluene at low levels have not
      been studied. The authors used serum-free mouse embryo cells-a precursor of
      astrocytes-to predict the effect of chemicals on developing brain cells. When
      serum-free mouse embryo cells were exposed to low levels of toluene, induction of
      glial fibrillary acidic protein was inhibited. This study demonstrated that
      environmentally relevant low levels of toluene could disrupt normal prenatal
      brain development.

PMID- 12507178
TI  - Clinical findings for residents near a polyurethane foam manufacturing plant.
AB  - Clinical findings for 38 community residents who complained of symptoms they
      attributed to exposure to air emissions from nearby fiber processing and
      polyurethane foam manufacturing facilities are reported. Common complaints
      included headache, mucosal irritation, shortness of breath, chest tightness, and
      wheezing. Airway hyperreactivity, measured by methacholine challenge, was
      observed in 8 individuals (22% of those tested), who also reported temporal
      relationships between exposure to visible emissions or odors and symptoms
      consistent with environmentally induced asthma. Six individuals (18.2%) had
      antibodies to at least 1 of the 3 common industrial diisocyanates. The number of
      individuals with antibodies to diisocyanates, coupled with the absence of other
      diisocyanate exposure, was highly suggestive of environmental exposure. The
      findings raised concern that some residents may have become sensitized to toluene
      diisocyanate.

PMID- 12507179
TI  - Nasal function in self-reported chemically intolerant individuals.
AB  - Nasal function has not yet been investigated under controlled exposures in
      individuals with self-reported Multiple Chemical Sensitivity (sMCS). Therefore,
      anterior rhinomanometry and acoustic rhinometry were applied in 12 individuals
      with sMCS, and 12 age-matched controls. The sMCS individuals and controls were
      selected on the basis of a standardized questionnaire. Controlled 4-hr exposures
      to ethylbenzene and 2-butanone were performed during 4 sessions. Exposures were
      close to the current German threshold limit values, and they approximated odor
      thresholds. Subjects with sMCS had a significant decrease in the flow value in
      anterior rhinomanometry, independent of substance and doses, compared with
      controls. This result suggests somatic reactions to the exposure. The result must
      be confirmed in additional studies, and pathophysiological examinations must be
      performed. For these investigations, anterior rhinomanometry was usable, but
      acoustic rhinometry can be recommended only after sufficient standardization has
      occurred. Furthermore, biochemical parameters of nasal mucosa must be considered.

PMID- 12507180
TI  - Urinary 1-hydroxypyrene levels in workers exposed to coke oven emissions at
      various locations in a coke oven plant.
AB  - Polycyclic aromatic hydrocarbons, which are carcinogenic and mutagenic to humans,
      are primary compounds in coke oven emissions generated by the coking process. The
      authors examined the relationship between coke oven workers' urinary 1
      hydroxypyrene levels and their exposure to polycyclic aromatic hydrocarbons, as
      determined on the basis of work category and pre- and postshift effects in a
      steel plant in Taiwan. Eighty-eight coke oven workers constituted the exposed
      group, and 61 office workers in a steel plant located 1.5 km from the coke plant
      constituted the control group. The benzene-soluble fraction in personal air
      samples, and 1-hydroxypyrene in urine samples, were measured for 3 consecutive
      days. The 3-day urinary 1-hydroxypyrene sampling results for topside workers
      (i.e., those most heavily exposed to emissions) in the coke oven group, and for
      the control group, as determined from postshift geometric means, were 23.8
      microg/gm creatinine and 0.3 microg/gm creatinine, respectively. These values
      increased to 13.4 and 0.1 microg/gm creatinine, respectively, after an 8-hr work
      period. The major source of polycyclic aromatic hydrocarbons for the exposed
      group was occupational; therefore, the closer workers were to the coke oven, the
      greater their exposure, and, consequently, the greater their metabolite level.
      Urinary 1-hydroxypyrene levels of the exposed group were 80 times higher than
      those of the control group. Smoking had no significant effect on the excretion of
      urinary 1-hydroxypyrene. 1-hydroxypyrene levels in the workers' urine during an 8
      day period was cumulative (half-life = 18.6 hr). The authors concluded that it
      would be desirable to switch highly exposed workers to a low-exposure work area,
      after a period of rest. In addition, urinary 1-hydroxypyrene was a confirmed,
      useful biological indicator for exposure to polycyclic aromatic hydrocarbons.

PMID- 12507181
TI  - Hyperbaric oxygen: an evidence based approach to its application.

PMID- 12507182
TI  - A systematic review of the literature reporting the application of hyperbaric
      oxygen prevention and treatment of delayed radiation injuries: an evidence based
      approach.
AB  - The treatment of delayed radiation injuries (soft tissue and bony radiation
      necrosis) is one of thirteen conditions approved by the Hyperbaric Oxygen Therapy
      Committee of the Undersea and Hyperbaric Medical Society as appropriate
      indications for hyperbaric oxygen (HBO2). This paper provides a systematic review
      of the literature reporting the results of HBO2 therapy in the treatment and/or
      prophylaxis of delayed radiation injury. Since the introduction of the concept of
      evidence based medicine, the medical community in general has set out to apply
      more critical and stringent standards in evaluating published support for
      therapeutic interventions. Evidence based medicine is designed to discover the
      best evidence available and apply it in daily practice for treatment of the
      individual patient. The preferred level of evidence is the randomized controlled
      trial, however, other evidence has merit as well. In this review, seventy-four
      publications are represented reporting results of applying HBO2 in the treatment
      or prevention of radiation injuries. These are appraised in an evidence-based
      fashion by applying three established systems of evaluation. All but seven of
      these publications report a positive result when HBO2 is delivered as treatment
      for or prevention of delayed radiation injury. These results are particularly
      impressive in the context of alternative interventions. Without HBO2, treatment
      often requires radical surgical intervention, which is likely to result in
      complications. Other alternatives including drug therapies are rarely reported,
      and for the most part have not been the subject of randomized controlled trials.
      Based on this review, HBO2 is recommended for delayed radiation injuries for soft
      tissue and bony injuries of most sites. Of note, an increasing body of evidence
      supports HBO2 for radiation-induced necrosis of the brain. For other radiation
      induced neurological injuries, additional study is required before
      recommendations for routine hyperbaric therapy can be made.

PMID- 12507183
TI  - The effect of air bubbles on rabbit blood brain barrier.
AB  - Several investigators have claimed that the blood brain barrier (BBB) may be
      broken by circulating bubbles, resulting in brain tissue edema. The aim of this
      study was to examine the effect of air bubbles on the permeability of BBB. Three
      groups of 6 rabbits were infused an isoosmotic solution of NaCl w/macrodex and 1%
      Tween. The solution was saturated with air bubbles and infused at rates of 50-100
      ml hr(-1), a total of 1.6, 3.3, or 6.6 ml in each group, respectively. Two
      groups, each consisting of 6 rabbits, served as controls; one was infused by a
      degassed isoosmotic NaCl solution and one was sham-operated. All animals were
      left for 30 min before they were sacrificed. Specific gravity of brain tissue
      samples was determined using a brombenzene/kerosene gradient column, where a
      decrease in specific gravity indicates local brain edema. Specific gravity was
      significantly lower for left (P = 0.037) and right (P = 0.012) hemisphere white
      matter and left (P = 0.0015) and right (P = 0.002) hemisphere gray matter for the
      bubble-infused animals compared to the sham-operated ones. Infusion of degassed
      NaCl solution alone affected white left (P= 0.011) and right (P= 0.013), but not
      gray matter of both hemispheres. We speculate that insufficient degassing of the
      fluid may cause the effect of NaCl solution on the BBB of the white matter,
      indicating that the vessels of the white matter are more sensitive to gas bubbles
      than gray matter. Increasing the number of infused bubbles had no further impact
      on the development of cerebral edema, indicating that a threshold value was
      reached already at the lowest concentration of bubbles.

PMID- 12507184
TI  - Effect of air diving exposure generally encountered by recreational divers:
      oxidative stress?
AB  - Long term effects on respiratory function have been found in air divers and have
      indicated the development of small-airway disease. These effects have been
      attributed to oxygen toxicity or to venous gas micro emboli (VGM). The airway
      obstructions observed in air divers raise fundamental questions about whether
      these alterations exist after one simulated dive. The aim of this report was to
      study the oxidative stress induced by brief normobaric hyperoxia (FiO2 = 0.6 for
      30 min) by measuring breath-exhaled compounds. Oxidative stress was measured by
      pentane in the expirate of 7 subjects ventilated with hydrocarbon-free air (HFA)
      before and after the hyperoxic exposure. NO concentration allowed us to determine
      the inflammatory response in the airway. Venous blood was drawn before and after
      the O2 breathing period for measurements of malondialdehyde (MDA). In all seven
      subjects, pentane elimination rates on 60%O2 do not increase after hyperoxia. NO
      rates during the HFA and hyperoxic exposures are significantly increased (p <
      0.05). MDA concentrations are not changed after the hyperoxic exposure. Pulmonary
      function parameters obtained 225 minutes after hyperoxia are not changed. These
      results provide evidence that a dry gas and oxygen breathing (FiO2 = 0.6) for 30
      min can raise exhaled NO. Oxidative stress assessed by pentane and MDA does not
      exist. We conclude that dry gas and the mild, 30 minute hyperoxic exposure,
      frequently encountered by recreational divers may be responsible for an airway
      inflammation. The consequences of such chronic exposure remains to be
      established.

PMID- 12507185
TI  - Hyperbaric oxygenation affects rat brain function after carbon monoxide exposure.
AB  - The application of hyperbaric oxygenation (HBO2) has been recommended for
      correction of neurological injury in severely CO-poisoned patients. However, the
      mechanisms of HBO2 action on brain mitochondrial function under the circumstances
      is not yet understood completely. In the present study, the effect of HBO2 on the
      rat brain after CO exposure was evaluated by measuring the intramitochondrial
      NADH and its responses to anoxic test or repetitive induction spreading
      depression (SD) leading to brain activation. A unique monitoring system for
      bilateral monitoring of brain NADH redox state was used. Rats were exposed to
      3000 ppm CO for 30 (group A) or 60 min (C). In groups B and D, after CO exposure,
      the rats were exposed to HBO2 (3 atm abs for 30 min). Following CO exposure in
      groups A and C, a definite decrease in the amplitude of the NADH response and
      significant increase in the number of waves of NADH was noted during induced
      cortical SD. Anoxic test in these two groups led to a significant decrease of
      maximum levels of NADH (reduction) at the end of observation. The amplitude, and
      the number of SD waves and magnitude of NADH deviation during anoxic test in
      group B after application of HBO2, was not significantly different from the
      values measured under the initial conditions. However, in group D, tendency of
      maintenance of the parameter's initial level was weaker or absent. The results
      obtained indicated that suppression of brain energy metabolism is a
      characteristic manifestation of CO poisoning in rats. Restoration of cerebral
      energy metabolism by adequate dosage of HBO2 may become an important factor for
      recovery of brain activities after CO poisoning.

PMID- 12507186
TI  - Heart rate of Japanese male ama divers during breath-hold dives: diving
      bradycardia or exercise tachycardia?

PMID- 12507187
TI  - Reassessment of theophylline use for severe asthma exacerbation: is it justified
      in critically ill hospitalized patients?
AB  - In the 1990s, numerous double-blind, randomized, placebo-controlled trials
      revealed that theophylline therapy offered no benefit to inhaled beta2 agonists
      and systemic corticosteroids in the treatment of patients hospitalized for asthma
      exacerbations. Routine use of theophylline in patients hospitalized for asthma is
      no longer advocated due to the potential for serious adverse effects and lack of
      benefit. However, the question remains whether this drug adds any benefits in
      critically ill patients who are being admitted to an intensive care unit. Two
      recent pediatric studies suggest that theophylline therapy may have a role in the
      management of patients with impending respiratory failure who have failed
      aggressive treatment with inhaled beta2 agonists, systemic corticosteroids, and
      inhaled ipratropium. If a patient has failed to respond adequately to high-dose
      routine therapies, theophylline should be initiated by a clinician who is
      competent in dosing, monitoring serum concentrations, and assessing factors that
      modify clearance of this high-risk drug. Further clinical research is needed to
      verify the value of theophylline in adults and children with severe asthma
      exacerbations and impending respiratory failure.

PMID- 12507188
TI  - Access to spacers and peak flow meters among medicaid patients with asthma.
AB  - Asthma morbidity and mortality have increased at alarming rates. Morbidity is
      significantly higher among minorities and low-income populations. The purpose of
      this study was to survey pharmacies licensed to provide both asthma medications
      and durable medical equipment (DME) to evaluate their acceptance of Medicaid as
      payment for spacers and peak flow meters in patients with Medicaid. Twenty-four
      pharmacies were identified and completed a telephone survey. Only 64% of the
      pharmacies licensed to accept Medicaid for DME provide this service. We postulate
      that improving DME licensing and claims reimbursement will impact medication
      compliance, as well as asthma morbidity and mortality.

PMID- 12507189
TI  - The prognosis of bronchial asthma in childhood in Hungary: a long-term follow-up.
AB  - The aim of this study was to determine the prognosis of bronchial asthma in
      childhood in Hungary. One hundred and forty five adults (96 men and 49 women)
      with a clinical history of childhood bronchial asthma were examined at the age of
      28 years or above (mean age 37.6, SD 5.9 years). The patients completed
      questionnaires concerning their asthmatic and accompanying allergic symptoms in
      childhood, at the age of 18 and at present. They were all prick-tested with 12
      inhalant allergens. The results showed that 42.8% of the patients had become
      symptom-free, but 57.2% still had intermittent or persisting asthmatic symptoms
      in adulthood. More patients had intermittent day-time (59%) and night-time (67%)
      asthmatic symptoms than persistent symptoms (41% and 33%). Accompanying allergic
      diseases (rhinitis, conjunctivitis, dermal and gastrointestinal diseases, and
      drug andfood allergies) in childhood did not definitely affect the prognosis of
      the bronchial asthma. The proportion of females with allergic diseases increased,
      and among patients with skin diseases it was significantly higher than the
      proportion of affected males. At the age of 18, allergic rhinitis was more
      frequent than in childhood. The frequencies of other allergic disorders did not
      change significantly. In the patients with asthmatic symptoms, molds and cat-hair
      allergies were more frequent than in the symptom-free group. The long-term
      prognosis of bronchial asthma in childhood in Hungary is relatively good, but
      fewer than half of the patients became symptom-free. The complaints of most of
      the patients were mild, but one in seven of all the adults suffered from moderate
      or serious bronchial asthma. Household allergens may contribute to the
      persistence of asthmatic symptoms.

PMID- 12507190
TI  - What determines knowledge of asthma among young people and their families?
AB  - In this analysis, we sought to determine factors that predicted the level of
      asthma knowledge in a sample of adolescents with asthma and their parents. Eighty
      five young people aged 10-24 years attending tertiary care asthma clinics and 46
      of their parents answered validated respiratory and asthma knowledge
      questionnaires. Older adolescents were more knowledgeable about asthma than were
      younger adolescents (r=0.36, p=0.001). Young people with severe asthma (p=0.015)
      scored higher on the asthma knowledge questionnaire than those with mild/moderate
      asthma. Asthma knowledge among young people was related to that of their mothers
      (r=0.47, p=0.014), however, only age and the asthma knowledge of fathers
      significantly predicted adolescent asthma knowledge. Adolescents develop
      increasing autonomy for asthma self-management as they mature, but parents remain
      an important source of information about asthma for young people.

PMID- 12507191
TI  - High frequency of emergency room visits of asthmatic children on misty or foggy
      nights.
AB  - STUDY OBJECTIVES: To examine whether or not the presence of mist or fog affects
      respiratory conditions in asthmatic children. DESIGN: A retrospective study.
      PREPARATION AND METHODS: There were 754 visits by children with asthma to the
      emergency room at night (between 18:00 p.m. and 9:00 a.m.) during a two-year
      period. Meteorological data were checked at a local fire station and regional
      meteorological observatory. We evaluated the relation between meteorological data
      and the number of emergency room visits of asthmatic children. RESULTS: The mean
      number of asthmatic children who visited the emergency room was higher on misty
      or foggy nights than on clear nights (1.2 +/- 1.2 people/night vs. 0.8 +/- 0.9
      people/night, p<0.0001). Mist and fog had an increased odds ratio (OR) of
      emergency room visits of asthmatic children (1.74, p<0.001). In addition,
      increased OR was found for high atmospheric temperature (4.39, p<0.0001).
      Multivariate analysis showed mist and fog (p<0.0001), average atmospheric
      temperature (p<0.0001), and day-to-day change of temperature (p<0.05) were
      related to the number of asthmatic children (n=731, r=0.428, p<0.0001).
      CONCLUSIONS: Our results suggest that the presence of mist and fog causes the
      exacerbation of asthma in children. It is not clear which is related to the high
      frequency of emergency room visits of asthmatic children, airborne water droplets
      or the meteorological condition that causes mist or fog, but the prophylaxis for
      exacerbation may decrease the frequency of emergency room visits.

PMID- 12507192
TI  - The anatomy of asthma care visits in community family practice.
AB  - BACKGROUND: We know little about the activities that occur during asthma-related
      visits with primary care physicians. A better understanding of how time is spent
      during visits for asthma may facilitate the design of programs to enhance asthma
      disease management. OBJECTIVE: To describe the content of asthma visits made to
      family physicians. METHODS: Research nurses directly observed consecutive
      outpatient visits during two separate days in the offices of 138 community family
      physicians. Time was classified into 20 different behavioral categories using the
      Davis Observation Code, and compared for visits for asthma, visits for other
      chronic conditions, and visits for non-asthma-related acute illnesses during 3035
      visits by patients of all ages. RESULTS: Visits for asthma shared several
      characteristics with visits for other chronic conditions but were longer than
      visits for other chronic illnesses or for acute illness. Asthma visits were
      distinguished from both acute care and other chronic care visits by a greater
      percentage of time spent discussing patient compliance, evaluating patient
      knowledge, and providing smoking assessment and cessation advice. CONCLUSIONS:
      Visits for asthma are structured differently than acute care visits and
      specifically address issues important to asthma self-management. Future quality
      improvement initiatives should recognize, affirm, and enhance many current
      behaviors by family physicians, while working to expand specific areas of care
      that still fall short of asthma care guidelines.

PMID- 12507193
TI  - Relationships between self-reported asthma utilization and patient
      characteristics.
AB  - BACKGROUND: Identifying asthmatic individuals most likely to utilize medical care
      in the future will help to direct intervention and medical resources; however,
      there are currently limited models for future utilization. OBJECTIVE: This study
      investigated the relationship between patient characteristics and medical
      utilization, using an asthma disease management patient population. METHODS: We
      analyzed a sample of 1412 adults, enrolled for 6 months in an asthma disease
      management program, for relationships with utilization. Individuals answered
      demographic, socioeconomic, and medical questions via telephonic contact upon
      enrollment. Follow-up regarding medical utilization occurred during the
      subsequent 6 months. Relationships between utilization and enrollment answers
      were statistically modeled. RESULTS: Oral steroid bursts, day and night symptom
      frequencies, age, gender, education level, and employment status all had a
      significant relationship to medical utilization. Those individuals who had used
      oral steroids 6 months prior to enrollment, patients with more than five night
      time asthma symptoms per month, and those with "continuous" day symptoms were
      more likely to report utilization. Those patients under 44 years old, females,
      those who were not high school graduates, and patients who defined themselves as
      unemployed because of their asthma were also more likely to report utilization.
      While those unemployed because of asthma were already more likely to report
      utilization, individuals in the 45+ age category were more likely than those 18
      44. CONCLUSIONS: Identifying asthma patients likely to utilize medical care is
      feasible, although more investigation is needed to demonstrate applicability to a
      general asthma population.

PMID- 12507194
TI  - Bronchodilator response in asthmatic children is significantly reduced when
      measured immediately after methacholine challenge.
AB  - AIM: Airway responses to a bronchodilator (BDR) and to methacholine are
      frequently measured in the assessment of childhood asthma and in pulmonary
      research. For practical reasons, we wondered whether it would be possible to
      obtain a reliable BDR immediately after completion of a methacholine challenge
      test. To this end, we compared BDR with and without a preceding methacholine
      challenge. METHODS: The BDR was measured twice in random order on consecutive
      days in 24 asthmatic children with methacholine hyperresponsiveness. It was
      calculated as the change in forced expiratory volume in one second (FEV1) before
      and 20 min after inhaling 800 microg of salbutamol (metered dose inhaler with a
      spacer), expressed as a percentage of the predicted value (deltaFEV1%pred). On
      one day BDR was measured immediately after completing a methacholine challenge,
      on the other day without any preceding challenge. RESULTS: Mean(SD) baseline
      FEV1%pred was not significantly different between test days [98.6(14.2)% and
      98.1(13.8)%, respectively, p=0.53]. The geometric mean provocative dose of
      methacholine producing a 20% fall in FEV1 (PD20) was 56.2 microg (range 10.3
      306.2 microg). The mean (SEM) BDR without preceding methacholine challenge was
      10.8(1.4)%, while after preceding methacholine challenge it was 5.2(1.5)% (mean
      difference 5.6%, 95% CI 3.0%-8.1%, p<0.001). Mean(SEM) postbronchodilator
      FEV1%pred was 109.4(3.0)% without and 103.4(2.7)% with preceding methacholine
      challenge (mean difference 6.0%, 95% CI 3.5%-8.6%, p<0.001). CONCLUSION: A
      preceding methacholine challenge significantly reduces BDR in asthmatic children.
      Therefore, a BDR, measured immediately after completing a methacholine challenge,
      cannot be used as a substitute for a separate bronchodilator test.

PMID- 12507195
TI  - Asthma knowledge and medication compliance among parents of asthmatic children in
      Nanjing, China.
AB  - Asthma knowledge and medication compliance among parents of 150 asthmatic
      children in Nanjing were assessed using a self-administered questionnaire. The
      results showed that 54.7% of parents had poor knowledge of asthma and its
      management. Parental compliance with medication was also suboptimal as only 43.3%
      of parents reported adherence with prescribed anti-asthmatic medication for their
      children. Reasons for non-compliance included fear of medication side-effects and
      tolerance, and forgetting to give the child's medication. Education and
      occupation were found to be associated with asthma knowledge, however there was
      no association between age or income with knowledge. Income was associated with
      compliance with asthma medication, however no association was found between
      parents' age, education, occupation, or asthma knowledge with compliance. This
      study has identified the need for accurate and up-to-date information on asthma
      for parents of asthmatic children as well as programs aimed at teaching parents
      skills in managing their child's asthma. There is also the need for strategies
      aimed at improving communication between the health provider and parents of
      asthmatic children.

PMID- 12507196
TI  - Relationship satisfaction moderates the association between catastrophic
      cognitions and asthma symptoms.
AB  - The tendency to have catastrophic beliefs and interpretations when anxious has
      been associated with less optimal disease management among persons with asthma.
      The goal of the present study was to examine the mediating effect of relationship
      satisfaction on the association between catastrophic cognitions and asthma
      symptom reporting in a sample of couples in which one partner has asthma. The
      participants were 50 patients with mild-to-moderate asthma and their partners.
      The results indicated that catastrophic cognitions were significantly associated
      with greater asthma symptoms related to rapid breathing, irritability, and
      panic/fear, after controlling for asthma severity. Among participants with high
      relationship satisfaction, catastrophic cognitions were significantly associated
      with panic/fear, irritability, anger, and loneliness. Among participants with low
      relationship satisfaction, catastrophic cognitions were significantly associated
      with dyspnea, congestion, and rapid breathing. These results are discussed in
      terms of potentially reflecting patients' perceptions of the fit between their
      coping needs and the support available in their intimate relationships.

PMID- 12507197
TI  - Asthma control and patient satisfaction among early pediatric users of
      montelukast.
AB  - OBJECTIVE: To assess asthma control and patient satisfaction among pediatric
      users of montelukast in a clinical practice setting. STUDY DESIGN: A prospective
      study of 175 children with persistent asthma, 6 to 14 years of age, who initiated
      treatment with montelukast between Feb-1998 and Aug-1998, in primary care and
      pediatric offices across the United States. Data on asthma control and
      satisfaction with treatment was collected in physicians' offices after enrollment
      and by survey to the patients' homes at 1 month of treatment. RESULTS: Across the
      study population, improvements in mean scores for asthma control and parent
      satisfaction were observed at the 1-month follow-up compared with baseline. At 1
      month, 57.7% of patients had none offour issues indicative of poor asthma
      control, compared with 19.4% at baseline. Similarly, after 1 month of treatment
      with montelukast, 2.7 times as many parents reported being very satisfied with
      asthma therapy (using montelukast) compared with the previous controller therapy
      regimen at baseline. During the 1-month follow-up period, montelukast was used as
      the only controller medication by 18.3% of patients, and in combination with
      another controller medication by 81.7%. CONCLUSIONS: Observations from this study
      over one month suggest that a significant percentage of pediatric patients
      successfully managed their asthma with montelukast and their parents were
      satisfied with their medication, compared to baseline.

PMID- 12507198
TI  - Implementation of asthma guideline in Taiwan--the management in medical centers.
AB  - The asthma guideline was published in Taiwan in 1995. In order to understand the
      implementation of the guidelines and patients' attitudes to inhaled
      corticosteroid (ICS), in 1999, we conducted two studies: one by reviewing medical
      records of 230 stable asthmatic patients cared for by 23 pulmonologists in four
      medical centers and another through aface-to-face questionnaire survey for 246
      asthmatic patients at the outpatient clinics. The results revealed that oral
      bronchodilators were prescribed to 85.7% (197/230) of the patients, while inhaled
      beta2 agonists were prescribed to 66.1% (152/230) of the patients. Inhaled
      corticosteroids and oral corticosteroids were prescribed to 120 (52.2%) and 64
      (27.8%) patients, respectively. Twenty-three (10%) patients were treated with
      oral corticosteroids without prescription of ICS. Only 25 (10.9%) patients had
      records of peak expiratory flow (PEF) every month. Thirty-eight (16.5%) patients
      sometimes measured PEF. The remaining 167 (72.6%) patients never measured PEF.
      The face-to-face questionnaire survey revealed that 56.5% (139/246) of the
      patients worried about adverse reactions of corticosteroids. Among them 40
      (16.3%) patients were very worried about it. Only 101 of 189 (53.4%) patients
      currently using ICS took the daily doses according to doctor's orders. Seventy
      four (39.2%) patients decreased the dose and 14 (7.4%) patients actually did not
      take ICS. In the 57 patients not treated with ICS, 13 (22.8%) patients answered
      that they would refuse to take ICS. In conclusion, the adherence to asthma
      guidelines is suboptimal for pulmonologists in the medical center. Poor adherence
      to asthma guidelines may be due to doctors' behavior and patients' attitudes.

PMID- 12507199
TI  - Pathogenesis of colorectal cancer.
AB  - It is frequently stated that all but a few colorectal cancers arise in
      adenomatous polyps, in turn initiated by APC mutation. Moderation of this view is
      now required. The proportion of colorectal cancers that arises in a polypoid
      adenoma is likely to be around 70% [39,61]. The pre-eminence of the adenoma
      carcinoma model has been influenced by two factors: (1) the need to avoid
      overtreatment of innocent lesions, and (2) the absence of a convincing
      alternative mechanism. The latter position has changed in recent years.
      Collectively, the alternative pathways may account for the pathogenesis of up to
      30% of colorectal cancers. The alternative pathways are difficult to observe in
      clinical practice because the precursors may be either inconspicuous or show
      rapid evolution following the establishment of genetic instability. As a concept,
      the polyp-cancer sequence is entrenched in both specialized and student texts.
      This is unfortunate, because progress in prevention and early cancer detection
      will be delayed by the failure to adopt a critical and nondogmatic approach to
      the pathogenesis of colorectal cancer. The advent of DNA chip technology will
      catalyze the development of revised paradigms. Specifically, modern genomics will
      allow polyps and cancers to be grouped within pathogenic pathways on the basis of
      shared gene expression profiles. The era of molecular medicine has dawned for
      colorectal cancer.

PMID- 12507200
TI  - Epidemiology and prevention of colorectal cancer.
AB  - CRC, the second-leading cause of cancer death in the United States, is a highly
      preventable disease. Ironically, available and effective screening technologies
      are not consistently applied, even as new ones are developed. This discordance
      between preventive opportunity and practice conveys a sobering message regarding
      nontechnologic issues that must be addressed if the promise of CRC prevention is
      to be realized. Our response to this message will determine the public health
      impact of cancer prevention. In the 1980s, cancer chemoprevention was regarded as
      scientific speculation. Within the last decade, however, cancer has been
      recognized as a late, nonobligate stage of carcinogenesis, a chronic process that
      provides time and targets for preventive intervention. Further advances are
      emerging out of rigorous clinical testing, which remains the limiting factor in
      transforming ingenious concepts into useful tools for the prevention of CRC. The
      challenges and rewards of participation in chemoprevention research--both as
      patients and health care providers-have never been greater.

PMID- 12507201
TI  - Colorectal cancer screening.
AB  - During the past decade we have seen dramatic advances in colon cancer screening.
      Reduction in mortality in average risk screening for colorectal cancer has now
      been shown in multiple trials. Efforts to increase public awareness and
      compliance with evidence-based screening guidelines are underway. Recent
      guidelines have incorporated family history, as it has been identified as a
      common risk factor. The genes responsible for the inherited syndromes of colon
      cancer have been identified and genetic testing is available. Currently,
      screening the average risk population over the age of 50 would reduce mortality
      from colon cancer by 50%. Future advances will likely include improved screening
      tests, and the development of familial genetic testing.

PMID- 12507202
TI  - Surgical management of malignant colorectal polyps.
AB  - The anatomic landmarks of the depth of invasion for pedunculated lesions (Haggitt
      level) and the Sm system for the sessile lesions give excellent objective
      information in the management of malignant colorectal polyps. Malignant polyps
      with low risk of lymph node metastasis include pedunculated lesions with invasion
      into Haggitt levels 1, 2, and 3. Level 4 pedunculated lesions and sessile lesions
      in which the invasion is into Sm1 or Sm2 level also have low risk if there are no
      adverse factors. These lesions can be treated by a complete local excision.
      Lesions that have high risk of lymph node metastasis are those with invasion into
      the lower third of the submucosa (Sm3), lesions that contain lymphovascular
      invasion, and lesions sited in the lower third of the rectum. These lesions
      require an oncologic colorectal resection. For lesions in the distal third of the
      rectum, a per anal full-thickness excision followed by an adjuvant chemoradiation
      may be an alternative. The box below summarizes malignant colorectal polyps
      requiring oncologic bowel resections:

PMID- 12507203
TI  - Local therapy for rectal cancer.
AB  - Local procedures for carefully selected distal rectal cancer offer significant
      advantages such as sphincter preservation and avoidance of radical surgery.
      However, since preoperative selection criteria including current imaging
      modalities are unable to definitively stage regional lymph node status, local
      therapies for rectal cancer have the inherent potential disadvantage of
      undertreating a fraction of patients due to unresected mesorectal/regional lymph
      node disease. Current available data suggests that the local approach may be
      appropriate only for carefully selected T1 tumors with favorable pathologic
      features. Inferior local control and survival reported for T2 tumors and T1
      tumors with unfavorable features, despite the addition of chemoradiation,
      outweigh the advantages of the local approach. Patients with unfavorable tumors
      who are unable to tolerate radical resection or who refuse surgery may be treated
      with local excision with or without adjuvant chemoradiation. Other modalities,
      such as electrocoagulation and endocavitary radiation, may also be valuable in
      this setting, as well as preoperative chemoradiation followed by local excision.
      Regardless of the approach used, all patients undergoing local therapy of a
      rectal cancer require careful long-term follow-up, because these patients remain
      at significant risk for local recurrence and distant failure.

PMID- 12507204
TI  - Rectal cancer: the sphincter-sparing approach.
AB  - There is considerable skepticism regarding sphincter-preserving surgery for
      rectal cancer, and 40% to 60% APR rates are reported in many prospective studies.
      Despite radical surgery, 20% positive margin rates are frequently reported.
      Rectal carcinoma responds to preoperative chemoradiation therapy with a 10% to
      15% pathologic complete response rate. Preoperative therapy offers an opportunity
      to reduce the positive margin rate and to reduce the APR rate. Because there is
      significant tumor regression with preoperative therapy, distal margins of less 1
      cm are acceptable and do not result in suture line recurrence. APR rate of less
      than 10% is feasible and better chemotherapy with radiation therapy will reduce
      the APR to less than 5%.

PMID- 12507205
TI  - The role of total mesorectal excision in the management of rectal cancer.
AB  - During the past decade, it has been clearly demonstrated that adjuvant treatment
      has the potential of improving not only prognosis in terms of local recurrence,
      but also in terms of overall survival. However, one of the largest improvements
      in the outcome of rectal cancer has been the introduction of total mesorectal
      excision. TME, with its large decline in local recurrence rate, has become the
      new standard of operative management for rectal cancers, replacing conventional
      resection technique [68]. In addition, current clinical trials examining the role
      of adjuvant therapy in patients who are undergoing standardized operations are
      now setting the standard of surgical care in several countries.

PMID- 12507206
TI  - Autonomic nerve preserving total mesorectal excision.
AB  - The main objectives of surgery for rectal cancer are cure and the prevention of
      local or pelvic recurrence. Preservation of pelvic autonomic functions are
      important associated goals that have influenced the design of the operation.
      These changes began with modifications to the art of lateral pelvic
      lymphadenectomy, and with the introduction of sharp pelvic dissection along
      anatomical pelvic fascial planes for rectal cancer in the mid-1970s. These
      changes evolved to include deliberate autonomic nerve preservation as a part of
      the operation that was ultimately reported as TME with ANP [1]. While it is a
      small nuance. dissection was generally directed to the widest possible pelvic
      margin--medial to the autonomic nerves, as opposed to just peripheral to the
      mesorectum. Both sexual and urinary functions are complex. and patients
      undergoing surgery for rectal cancer may have differing baseline levels of
      function. Pre-existing benign prostatic hypertrophy or stress incontinence are
      common physical conditions. Patients bring personal or cultural attitudes to the
      subject of sexual function with advancing years. in a population with a median
      age in the mid-sixties. Other health issues such as coronary artery or peripheral
      vascular atherosclerotic disease, diabetes mellitus. smoking or alcohol intake,
      or the use of medications to treat these conditions, may influence sexual
      function. Radiation therapy, frequently used in conjunction with chemotherapy in
      the treatment of rectal cancer, may be associated with its own incidence of
      impotence caused via a different mechanism. While radiation may affect the vasa
      nervosa of the autonomic nerves, leading to fibrosis and dysfunction. radiation
      therapy may also be associated with smooth muscle fibrosis, causing vasculogenic
      impotence due to penile outflow dysfunction in the corpora cavernosa. The causes
      of impotence after surgery alone or after surgery. radiation, and chemotherapy
      for rectal cancer are complex, and not all answers to the problem reside in
      autonomic nerve-preservation. Attention to all of the potential causes of
      impotence and of urinary dysfunction will require continued longitudinal research
      by clinical investigators from multiple disciplines.

PMID- 12507207
TI  - The role of laparoscopy in the multimodality treatment of colorectal cancer.
AB  - Ten years after the first reports of laparoscopic techniques in colorectal
      surgery the precise role for these approaches in future colorectal practice as
      still to be defined. However, it seems most unlikely that the application is
      going to disappear. Laparoscopic colectomy is undoubtedly a complex. time
      consuming procedure and it is clear that the technique is intolerant of difficult
      cases and will likely remain thus. Therefore. the potential advantages of
      laparoscopy do not as yet appear to be attainable across the board in colorectal
      resection. Such generalized advantage may, however, be tantalizingly close.
      Although many studies have failed to show major benefits for laparoscopy in terms
      of postoperative recovery, it must be remembered that most of these have been of
      insufficient statistical power to settle the issue. What is clear to all involved
      in the field is that very many patients do gain major benefit from the minimally
      invasive approach. The challenge for the future lies in developing the technology
      to such a point that these benefits for patients are more reproducible. The
      requirement for a significant abdominal incision to deliver an intact specimen
      represents a significant hurdle in this regard. The importance of pathological
      staging for colorectal cancer at present mandates retrieval of an intact
      specimen. It is of course possible that radiological staging may develop to such
      a point that surgeons need only remove the lesion with minimal attention to
      lymphadenectomy. Alternatively, new adjuvant therapies may arrive that, by virtue
      of increased efficacy and low side-effect profiles, may be applicable to all but
      the earliest lesions. Finally, increasing health awareness and application of
      screening programs may lead to a preponderance of large polyps and preinvasive
      lesions for which a more limited resection may be appropriate. Obviously these
      scenarios remain almost entirely speculative. However, the trend towards less
      invasive local therapy for colorectal cancer seems inexorable, and we firmly
      believe that laparoscopy will come to play an increasing role. Finally, we
      suggest that the oncological safety of laparoscopy is of less concern than was
      the case some years ago. The specter of port-site metastasis, once so alarming,
      has faded. It is now apparent from all of the larger scale studies that port-site
      metastases are not a significant issue in the presence of adequate training and
      laparoscopic skills. Almost without exception, the accumulating evidence seems to
      point to equivalence in terms of disease-specific recurrence and survival between
      patients treated using conventional and laparoscopic techniques. We foresee these
      findings being confirmed by the North American and European trials.

PMID- 12507208
TI  - Adjuvant therapy of cancers of the colon and rectum.
AB  - Important advances have been made in our understanding of the role of adjuvant
      therapy for colorectal cancer. Current standard 5FU-based regimens have been
      convincingly shown to reduce the incidence of recurrences and to prolong overall
      survival in patients with resected stage III colon cancer. Colon cancer patients
      with stage II disease have a better-overall prognosis than those with stage III;
      however, the relative merits of adjuvant treatment in these patients remains
      controversial. Combined chemotherapy plus radiation therapy is currently the
      standard adjuvant approach for stage II and III rectal cancer patients. Despite
      the advances that have been made, far too many patients with resectable
      colorectal cancer ultimately relapse and die of their disease. There remains a
      pressing need for continued development of improved adjuvant treatments.
      Participation of eligible patients in clinical trials must continue to be
      actively encouraged. Only in this way will we be able to continue to build and
      expand on the progress that has been made thus far.

PMID- 12507209
TI  - Multimodality management of locally recurrent colorectal cancer.
AB  - The combined management of locally recurrent colorectal cancer shows considerable
      promise, but the best way to incorporate the different treatment modalities and
      the potential benefits remain uncertain. The case series mentioned here were
      derived from highly selected groups from a much larger population of patients
      with recurrent disease; thus fully combined management may be only appropriate
      for a minority of people with recurrent disease. There is a need for multicenter
      randomized trials to better delineate the real benefits from the combined
      approach. Multimodality management of recurrent colorectal cancer, however,
      involves more than the combination of surgery, radiation therapy, and
      chemotherapy for a select minority of resectable patients. It involves the use of
      each modality to its greatest advantage for all patients, as determined by a
      multidisciplinary team of specialists. We should also not confine our attention
      to the treatment aspects of recurrent disease alone, as the greatest promise for
      improved survival could be with a more general application of total mesorectal
      excision. Because most people who develop local recurrence of colorectal cancer
      will die from their disease, the main contribution of a multimodality approach
      may be towards palliation.

PMID- 12507210
TI  - Colorectal metastasis (liver and lung).
AB  - Distant metastases are the major cause of death for colorectal carcinoma
      patients. Depending on the primary tumor's stage, liver metastases occur in 20%
      to 70% of patients and lung metastases in 10% to 20%. Unlike many other cancers,
      the presence of distant metastases from colorectal cancer does not preclude
      curative treatment. Surgical resection remains the only treatment that can ensure
      long-term survival and cure in some patients, but only a minority of liver
      metastases are amenable to surgery. New treatment modalities including portal
      vein embolization, perioperative chemotherapy and local destruction with
      cryotherapy or radiofrequency ablation may make more patients suitable for
      surgical resection of hepatic metastases and may prolong survival in cases of
      nonresectabilitv. The availability of new active drugs has changed the treatment
      of liver metastases from colorectal cancer.

PMID- 12507211
TI  - The preoperative assessment and postoperative surveillance of patients with colon
      and rectal cancer.
AB  - Many advances have been made in the field of colorectal cancer follow-up since
      the pioneering efforts of Wangensteen and others with second-look operations in
      the 1950s. The understanding of the biology and natural history of colorectal
      malignancy has been advanced. Diagnostic methods for detection of recurrent
      disease have also advanced tremendously with CEA monitoring, immunoscintigraphy.
      CT, MRI, and PET imaging. As has been discussed in this article, however, no
      strategy of postoperative follow-up has been shown unequivocally to produce
      improved survival benefit or cure rate. It is quite possible that benefit will be
      shown, but well-controlled trials will be required. Cost considerations will
      likely prove important, because the rate of detection of curable disease will
      likely.be low. Quality of life issues will also be important in such trials.
      Better treatment and outcome ol recurrent disease would provide a strong
      rationale for vigorous postoperative surveillance. New recommendations are
      currently evolving [54]. Early diagnosis seems likely to enhance the curability
      of both local and distant relapses and second primary tumors. Furthermore, there
      may be a survival and quality of life advantage that results from the early
      institution of chemotherapy, even for those tumors found to be inoperable [55].
      In devising a plan for follow-up in patients, it is important to recognize the
      anatomic and temporal patterns of recurrence as well as their relationships to
      the initial tumor staging. Although there is little proof that the identification
      of recurrent disease in follow-up programs increases the likelihood of
      resectability, cure, or prolonged survival, many physicians have witnessed
      successful treatment of recurrent colorectal cancer. These anecdotal experiences,
      the unproven belief that follow-up is beneficial, and traditions imparted during
      training are among the likely motivating factors for most physicians caring for
      colorectal cancer patients.

PMID- 12507212
TI  - Nearly half of dental randomized controlled trials published in German are not
      included in Medline.
AB  - Randomized controlled trials (RCTs) are considered the most reliable type of
      clinical intervention studies. However, not all reports of RCTs are accessible in
      Medline. This can impede the validity of the results of systematic reviews. Ten
      German-language dental journals were manually searched to locate reports of
      controlled clinical trials published between 1970 and 2000. The publication type
      was determined and compared with Medline. Of the 15 777 articles, 210 reports of
      RCTs and 410 articles of non-randomized controlled clinical trials (CCTs) were
      identified. Only 56% of the RCTs and 75% of the CCTs are available in Medline. Of
      the 118 reports of RCTs registered in Medline. 15 are indexed with the correct
      Publication Type term. Our data suggest that (a) hand-searching plays a valuable
      role in identifying reports of clinical dental trials, and (b) a literature
      search in Medline is likely to yield incomplete results.

PMID- 12507213
TI  - The effect of oral temperature on the temperature perception of liquids and
      semisolids in the mouth.
AB  - This work examined the influence of oral temperature on oral perception of
      temperature in liquids and semisolids. A panel of 20 adults assessed the
      temperature of water, custard dessert and mayonnaise. Oral temperatures were
      manipulated by 5-s mouth rinses of 10, 35 and 55 degrees C performed prior to
      assessments, which resulted in oral temperatures of 27, 35 and 43 degrees C,
      respectively. The products were evaluated at 10, 22 and 35 degrees C. Results
      show that subjects were able to differentiate between the product temperatures. A
      large effect of type of product was seen on perceived temperature, where water
      was, overall, perceived as significantly colder than custard dessert and
      mayonnaise. The range of perceived thermal ratings was widest for custard
      dessert, followed by water and mayonnaise. This might be due to differences in
      composition and structure of the products. Even though oral temperature was
      varied considerably in the present study, this did not exert large effects on
      perceived temperature.

PMID- 12507214
TI  - Edentulousness and oral rehabilitation: experiences from the patients'
      perspective.
AB  - The psychological effects of tooth loss in the permanent dentition are relatively
      unknown. Complete edentulousness is a serious life event in terms of
      readjustment. The aim of the study was to describe the process patients with
      deteriorating dental status had gone through before treatment with a fixed
      prosthesis (Branemark System, Novum), and to describe what living with a fixed
      prosthesis means to the patients themselves. In-depth interviews were carried out
      with 18 patients, and the interviews were transcribed verbatim and analysed in
      open, axial and selective coding processes according to Grounded Theory. In the
      analysis, four categories were developed and labelled: 'alterations in self
      image', 'becoming a deviating person', 'becoming an uncertain person' and
      'becoming the person I once was'. 'Alterations in self-image' was identified as
      the core category and was related to the other three categories. The core
      category describes the changes in self-image starting with the subjects'
      increasingly worsened dental status, followed by a period of them having to live
      and cope with a denture and, finally, their living with a fixed prosthesis. The
      motive power for the decision to undergo treatment with a fixed prosthesis seems
      to be a desire to restore dental status and also to recapture attractiveness,
      self-esteem and a positive self-image.

PMID- 12507215
TI  - The German version of the Oral Health Impact Profile--translation and
      psychometric properties.
AB  - The need for cross-culturally adapted oral-health specific health outcome
      measures is increasingly recognized in Germany. Following accepted cultural
      adaptation technique guidelines, we report the development of the German version
      of the Oral Health Impact Profile (OHIP). The original 49 items were translated
      using a forward-backward method. A de novo development of German items
      established content validity. A priori hypothesized associations between the OHIP
      summary score and self-reported oral health and five oral disorders were
      confirmed in a random sample of the general population (n = 163, age 20-60 yr).
      These associations were interpreted as support for construct validity. The
      instrument's responsiveness, as indicated by a mean OHIP summary score change
      from 45.0 to 28.3, was established in 67 consecutive patients treated for
      temporomandibular disorder pain (age 19-85 yr; 72% women). Test-retest
      reliability was demonstrated by intraclass correlation coefficients of 0.63-0.92
      for dimensions and summary scores (convenience sample, n = 30, age 18-85 yr; 53%
      women). Internal consistency was high (Cronbach's alpha > 0.74). Sufficient
      discriminative and evaluative psychometric properties of the Oral Health Impact
      Profile German version (OHIP-G) make the instrument suitable for assessment of
      oral health-related quality of life in cross-sectional as well as longitudinal
      studies.

PMID- 12507216
TI  - Influence of dentifrices and dietary components in saliva on wettability of
      pellicle-coated enamel in vitro and in vivo.
AB  - In vitro salivary pellicles were found to be less hydrophobic by water contact
      angles than clinically formed pellicles. In this study, water contact angles were
      measured on enamel coated with pellicles adsorbed from reconstituted human whole
      saliva (RHWS) and after exposure to dentifrices or dietary components. In
      addition, adhesion of Streptococcus oralis J22 to pellicles formed from RHWS with
      minor amounts of milk added and after exposure to dentifrices was studied.
      Exposure of RHWS-pellicles to milk or salad oil yielded an increase in the
      hydrophobicity of in vitro pellicles to values observed in vivo, but a decrease
      was seen after exposure to a sugar solution. Pellicles formed from saliva with
      0.4% milk added attracted less S. oralis cells than pellicles formed in the
      absence of milk components. Exposure of pellicles formed from saliva with milk
      added to various dentifrices had a variable effect on bacterial adhesion:
      markedly lower numbers of adhering S. oralis were found for a dentifrice with
      NaF, but exposure to dentifrices containing SnF2 or hexametaphosphate showed
      slightly increased adhesion. In summary, dietary components have influence on the
      hydrophobicity of enamel pellicles, while combinations of dietary components and
      dentifrices certainly influence the adhesiveness of the pellicles. The effects of
      dietary components on pellicle conditioning film should be taken into
      consideration in research on the development of ingredients to control intraoral
      surface chemistry and microbiology, as well as in the development of oral
      products.

PMID- 12507217
TI  - Possible involvement of extracellular signal-regulated kinases 1/2 in mitogenic
      response of periodontal ligament cells to enamel matrix derivative.
AB  - The efficacy of enamel matrix derivative (EMD) as an adjunct to periodontal
      regenerative therapy has been demonstrated in recent clinical studies, however,
      little is known about its molecular mechanism (s). We examined the mitogenic
      response of cultured periodontal ligament (PDL) cells to EMD and characterized
      associated changes in proliferation-related intracellular signaling molecules,
      including mitogen-activated protein kinases (MAPK) and Akt kinases/protein kinase
      B (Akt/PKB) kinases. The DNA synthesis of PDL cells increased following treatment
      with EMD at concentrations higher than 1 microg ml(-1). This mitogenic response
      to EMD was associated with the selective activation of extracellular signal
      regulated kinase (ERK) 1/2. No other MAPKs, or Akt/PKB kinases, responded to EMD
      stimulation. The EMD induction of DNA synthesis and activation of ERK 1/2 were
      diminished by pretreatment with suramin, an inhibitor of receptor tyrosine
      kinases (RTK). The signaling pathway induced by EMD from RTK to ERK 1/2 was
      similar to that activated by epidermal growth factor (EGF), although the specific
      binding of 125I-EGF to PDL cells was not affected by pretreatment or concomitant
      treatment with EMD. These findings suggest that EMD elicits its mitogenic signal
      through an EMD-specific RTK towards ERK 1/2.

PMID- 12507218
TI  - On the role of MT1-MMP, a matrix metalloproteinase essential to collagen
      remodeling, in murine molar eruption and root growth.
AB  - Although the connective tissues of the periodontium are subject to a high
      turnover rate, no conclusive evidence has yet emerged that periodontal collagen
      turnover is essential for the eruption of teeth or for root elongation. These
      processes were studied in mice deficient in MT1-MMP, a membrane type matrix
      metalloproteinase essential for remodeling of soft tissue-hard tissue interfaces.
      Mandibular first molars of deficient mice and their wild-type littermates were
      subjected to stereological analysis in order to assess root length, eruption and
      the volume density of phagocytosed collagen in periodontal ligament fibroblasts.
      The data showed that both eruption and root elongation were severely inhibited in
      animals lacking the enzyme. We also found, in periodontal ligament fibroblasts
      from MT1-MMP-deficient mice, a massive age-related accumulation (up to 60-fold
      over controls) of collagen fibril-containing phagosomes. Phagolysosomes, which
      represent the next downstream step in collagen fibril degradation by the
      lysosomal pathway, did not accumulate. These observations indicate that MT1-MMP
      plays a central role in periodontal remodeling. The stunted root growth and the
      failure to erupt indicate the important role of the enzyme in tooth development.

PMID- 12507219
TI  - Prenatal morphogenesis of the human mental foramen.
AB  - The mental foramen, at first glance, merely looks like a hole where the mental
      nerve and the vascular bundle runs through. From a morphogenetic point of view,
      however, the mental foramen is a suitable model to study the development of a
      structure where different components are involved. To understand this
      developmental process, a three-dimensional description at different developmental
      stages first has to be given. From histological serial sections of human embryos
      and fetuses, ranging in size from 19 to 117 mm crown rump length (CRL), three
      dimensional reconstructions of the foraminar regions were made. Outline and form
      of the developing foramen, size, course of the mental nerve and the adjacent
      blood vessels could be shown in detail. In this way, the formation of these
      structures became concrete in three dimensions. In the future, to understand the
      mechanisms regulating this complex system, where a nerve and blood vessels became
      successively surrounded by bone, molecular biological data have to be correlated
      with morphological findings.

PMID- 12507220
TI  - Pulpal uptake of mercury from lined amalgam restorations in guinea pigs.
AB  - The aim of the present study was to examine pulp in amalgam-restored teeth of
      guinea pigs with respect to the presence of mercury, and to evaluate whether
      lining of cavities with resin modified glass ionomer cements had any effect on
      the penetration of mercury. Class V cavities were prepared in 63 incisor teeth of
      21 guinea pigs. Three amalgam restorations were placed per animal, one without
      base liner and two with different resin-modified glass ionomer cements (GC Lining
      LC and Ionoseal). Following observation periods of 1, 7 or 30 d, teeth were
      extracted and the mercury concentration in the pulp tissue was evaluated using
      atomic absorption spectrophotometry. It was found that resin-modified glass
      ionomer cements significantly diminished the transport of mercury into the pulp
      between day 7 and day 30 after amalgam insertion.

PMID- 12507221
TI  - Inter-crystallite nanoretention of self-etching adhesives at enamel imaged by
      transmission electron microscopy.
AB  - The purpose of this in vitro study was to analyse the mode of action of self
      etching adhesive systems when applied for resin-to-enamel bonding. Transmission
      electron microscopy was used to investigate the enamel-resin interface after
      application of non-rinsing self-etching adhesive systems based on phosphoric acid
      estered methacrylates (Clearfil Liner Bond 2, Clearfil SE Bond, Etch & Prime 3.0
      and Resulcin AquaPrime) compared with conventional phosphoric acid etching and
      bonding (Heliobond). Non-decalcified ultrathin sections from the interface
      between enamel and self-etching adhesive systems revealed a 1.5-3.2-microm deep
      enamel surface layer characterized by a less-dense arrangement of enamel
      crystallites separated from each other by nanometer-sized spaces. A 1.5-3.2
      microm wide, netlike resinous structure was observed in corresponding decalcified
      specimens, indicating that self-etching priming agents dissolve the peripheral
      and central part of the enamel crystallites, while simultaneously promoting inter
      and intra-crystallite monomer infiltration. A similar pattern, but greater depth
      (6.9 microm) of enamel surface hybridization was found in the phosphoric acid
      etched and bonded specimens. The nanoretentive interlocking between enamel
      crystallites and resin could explain the potential of self-etching adhesive
      systems in resin-to-enamel bonding despite the less distinct enamel etching
      pattern observed in scanning electron microscopy investigations.

PMID- 12507222
TI  - Effect of irradiation type (LED or QTH) on photo-activated composite shrinkage
      strain kinetics, temperature rise, and hardness.
AB  - This study compares commercially available light-emitting diode (LED) lights with
      a quartz tungsten halogen (QTH) unit for photo-activating resin-based composites
      (RBC). Shrinkage strain kinetics and temperature within the RBC were measured
      simultaneously using the 'deflecting disc technique' and a thermocouple. Surface
      hardness (Knoop) at the bottom of 1.5-mm thick RBC specimens was measured 24 h
      after irradiation to indicate degree of cure. Irradiation was performed for 40 s
      using either the continuous or the ramp-curing mode of a QTH and a LED light (800
      mW cm(-2) and 320 mW cm(-2), respectively) or the continuous mode of a lower
      intensity LED light (160 mW cm(-2)). For Herculite XRV and Filtek Z250 (both
      containing only camphoroquinone as a photo-initiator) the QTH and the stronger
      LED light produced similar hardness, while in the case of Definite (containing an
      additional photo-activator absorbing at lower wavelength) lower hardness was
      observed after LED irradiation. The temperature rise during polymerization and
      heating from radiation were lower with LED compared to QTH curing. The fastest
      increase of polymerization contraction was observed after QTH continuous
      irradiation, followed by the stronger and the weaker LED light in the continuous
      mode. Ramp curing decreased contraction speed even more. Shrinkage strain after
      60 min was greater following QTH irradiation compared with both LED units
      (Herculite, Definite) or with the weaker LED light (Z250).

PMID- 12507223
TI  - Toothbrushing affects the protein composition of whole saliva.
AB  - Saliva is increasingly used for diagnostic purposes, but little is known about
      the potential effect of toothbrushing on the composition of saliva. Therefore,
      saliva collected before and 0, 15, 30 and 45 min after toothbrushing according to
      the Bass method was analysed for relevant protein composition. The flow rate
      initially increased (+15%) after toothbrushing, followed by a decrease after 15
      min (-15%). The concentration of salivary immunoglobulin A (S-IgA) decreased (
      40%) whereas the albumin concentration increased (+400%) within 20 min. Flow rate
      and S-IgA concentration returned to baseline values within 30 min. The albumin
      concentration, however, was still increased after 45 min. No significant
      increases were observed in the concentrations of total protein and amylase. Our
      results show that toothbrushing has a significant effect on the protein
      composition of saliva, by contamination with serum constituents. This should be
      taken into account when saliva is used for diagnostic purposes.

PMID- 12507224
TI  - Pharmacogenomics in cancer drug discovery and development: inhibitors of the
      Hsp90 molecular chaperone.
AB  - Drug discovery is being revolutionised by a number of technological developments.
      These include high throughput screening, combinatorial chemistry and genomics.
      The impact of the new technologies is to accelerate the pace of anticancer
      discovery. The completion of the Human Genome Project and the ongoing high
      throughput sequencing of cancer genomes will facilitate the identification of a
      range of new molecular targets for drug discovery. Over the next few years we
      will have a complete molecular understanding of the various combinations of genes
      and cognate pathways that drive the malignant phenotype and tumour progression.
      The vision for postgenomic cancer drug discovery must be to identify therapeutic
      agents that correct or exploit each of these molecular abnormalities. In this
      way, it will be possible to develop personalised drug combinations that are
      targeted to the molecular make up of individual tumours. It is anticipated that
      these therapies will be more effective and less toxic than current approaches,
      although combinations of novel agents with existing cytotoxic therapies are
      likely to continue for some time. Examples of postgenomic, mechanism-based drugs
      include Glivec, Herceptin and Iressa, with many more agents undergoing
      preclinical and clinical development. An interesting new approach involves the
      development of inhibitors of heat shock protein (Hsp90) molecular chaperone.
      Because Hsp90 is required for the correct folding, stability and function of a
      range of oncoproteins that are mutated or over expressed in cancer, Hsp90
      inhibitors have the potential to provide a simultaneous, combinatorial attack on
      multiple oncogenic pathways. By depleting the levels of multiple oncoproteins in
      cancer cells and blocking a wide range of oncogenic pathways, Hsp90 inhibitors
      have the potential to inhibit all of the hallmark characteristics of cancer
      cells. Progress in the preclinical and clinical development of Hsp90 inhibitors
      will be described, including an update on clinical studies with the first-in
      class agent 17AAG. The use of the postgenomic technology of gene expression
      microarrays in cancer pharmacology and drug development will be exemplified.

PMID- 12507225
TI  - Modification of lung cancer susceptibility by green tea extract as measured by
      the comet assay.
AB  - Green tea is widely consumed throughout the world and is known to possess various
      beneficial properties that may affect carcinogen metabolism, free radical
      scavenging, or formation of DNA adducts. Therefore, it is plausible that green
      tea extract may modify BPDE-induced DNA damage. In this report, we utilized the
      comet assay to (1) evaluate BPDE-induced DNA damage as a potential marker of
      cancer susceptibility and (2) assess the ability of green tea to modify BPDE
      induced DNA damage. DNA damage in individual comet cells was quantified by (1)
      visually measuring the proportion of cells exhibiting migration versus those
      without and (2) the length of damaged DNA migration (comet tail). We detected a
      dose-response between BDPE concentration and mean comet tail length in EBV
      immortalized lymphoblastiod (lymphoid) cell lines. As the concentration of BPDE
      increased from 0.5 to 3 microM, the length of the mean comet tail length
      increased proportionally in the 3590P (derived from a healthy subject) and 3640P
      (derived from a patient with head and neck cancer) cell lines. In separate
      experiments using lymphoid cells from 21 lung cancer cases and 12 healthy
      subjects, the mean comet tail length was significantly higher in the lung cancer
      cases (80.19 +/- 15.55) versus the healthy subjects (59.94 +/- 14.23) (P < 0.01).
      Similar findings were observed when analyzing the mean percentage of comet
      induced cells (84.57 +/- 8.85 and 69.04 +/- 12.50, respectively) (P < 0.01). When
      green tea extract was added in conjunction with BPDE, there was a notable
      reduction of the mean comet tail length (13.29 +/- 0.97) as compared to BPDE
      treatment alone (80.19 +/- 15.55) (P < 0.01) in lung cancer cases. There were no
      statistical differences between the baseline (no treatments) (12.74 +/- 0.63) and
      the green tea extract treatment (13.06 +/- 0.97) (P = 0.21). These data suggest
      the modification of lung cancer susceptibility by the green tea extract. Similar
      results were observed for the percentage of induced comet cells and the
      statistical trends were similar for the 12 healthy subjects. This preliminary
      study demonstrated that the detection of BPDE-induced DNA damage via the comet
      assay may be a useful biologic marker of lung cancer susceptibility. The
      differential effects in BPDE-induced DNA damage between lung cancer cases and
      healthy subjects suggests predisposed cancer susceptibility to lung cancer risk.
      This reports also demonstrated the chemopreventive effects of green tea extract
      on BPDE-induced DNA damage. These observations provide further support for the
      application of the comet assay in molecular epidemiologic studies.

PMID- 12507226
TI  - Chemopreventive effect of farnesol and lanosterol on colon carcinogenesis.
AB  - Cholesterol metabolites play a several critical roles in regulating cell growth
      and function. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, the rate
      limiting enzyme for this pathway, is down regulated by feedback mechanisms due to
      increased levels of cholesterol and its premetabolites. Several HMG-CoA
      metabolites, such as farnesyl pyrophosphate and geranyl pyrophosphate are
      implicated in oncogene activation and tumorigenesis. Recent studies suggest that
      inhibition of HMG-CoA reductase by specific inhibitors or by naturally-occurring
      phytochemicals, such as farnesol or squalene can modulate tumor cell growth.
      Thus, in this study, we have assessed the chemopreventive efficacy of farnesol
      and lanosterol on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in
      rats. In addition, we measured the effect of farnesol and lanosterol on serum
      high denisity lipoprotein (HDL) and cholesterol levels in the rats. Seven-week
      old male F344 rats were fed the control diet (modified AIN-76A) or experimental
      diets containing I or 2% lanosterol or 1.5% farnesol. One week later, all animals
      except those in vehicle (normal saline)-treatment groups were s.c. injected with
      AOM (15 mg/kg body weight, once weekly for 2 weeks). At 16 weeks of age, all rats
      were killed, colons were evaluated for ACF and serum was assayed for HDL and
      cholesterol levels. Administration of dietary farnesol significantly inhibited
      ACF formation by about 34% (P < 0.001) and reduced crypt multiplicity by about
      44% (P < 0.0001). Also, administration of lanosterol at dose levels of I or 2 %
      in the diet significantly suppressed AOM-induced colonic ACF as well as
      multicrypt foci formation. (P < 0.01-0.001). Further, farnesol at 1.5% and
      lanosterol at 1% did not show any significant effect on serum HDL nor on total
      cholesterol levels. However, lanosterol at 2% significantly increased serum HDL
      (P < 0.05) and cholesterol (P < 0.01) levels. That farnesol and lanosterol
      significantly suppress colonic ACF formation and crypt multiplicity strengthens
      the hypothesis that these agents possess chemopreventive activity against colon
      carcinogenesis.

PMID- 12507227
TI  - Allelic loss in breast cancer.
AB  - Breast cancer is the most prevalent cancer type in women and allelic loss
      constitutes one of the commonest genetic alterations in mammary neoplasias.
      Frequent detection of Loss of Heterozygosity indicates genes with putative tumour
      suppressor activity in breast carcinomas. Imbalance between two alleles might
      also be related with increased expression of an oncogene within a locus. Loci
      exhibiting frequent allelic loss in breast cancer have been detected, spread
      throughout the genome, and may contain genes with potential significance in
      breast carcinogenesis. Loss of Heterozygosity patterns in breast cancer give
      evidence for multiple clonality of the disease, and that accumulation of such
      lesions is probably implicated in disease development. Studies on deletions of
      known breast cancer genes suggest interactions with other common genetic events
      during disease initiation and progression. Allelic loss has been repeatedly
      associated with adverse characteristics and poor outcome in breast neoplasms.
      Detection of allelic loss in the serum of breast cancer patients and in
      premalignant breast lesions could herald the potential for diagnosis of the
      disease at an early, and thus curable, stage.

PMID- 12507228
TI  - Transcriptional control of the RECK metastasis/angiogenesis suppressor gene.
AB  - The RECK gene is widely expressed in normal human tissues but is downregulated in
      tumor cell lines and oncogenically transformed fibroblasts. RECK encodes a
      membrane-anchored glycoprotein that suppresses tumor invasion and angiogenesis by
      regulating matrix-metalloproteinases (MMP-2, MMP-9 and MT1-MMP). Understanding of
      the transcriptional regulation of tumor/metastasis suppressor genes constitutes a
      potent approach to the molecular basis of malignant transformation. In order to
      uncover the mechanisms of control of RECK gene expression, the RECK promoter has
      been cloned and characterized. One of the elements responsible for the Ras
      mediated downregulation of mouse RECK gene is the Sp1 site, to which Sp1 and Sp3
      factors bind. Other regulatory events, such as DNA methylation of the RECK
      promoter and histone acetylation/deacetylation have been studied to understand
      the underlying mechanisms of RECK expression. Understanding of the mechanisms
      which control RECK gene transcription may lead to the development of new
      strategies for cancer prevention and treatment.

PMID- 12507229
TI  - Differential expression of DNA-methyltransferases in drug resistant murine
      neuroblastoma cells.
AB  - Neuroblastoma tumors frequently become drug resistant during the process of
      chemotherapy resulting in unfavorable clinical outcomes. Development of sustained
      drug resistance in neuroblastoma is a major problem in successful treatment. To
      explore the role of DNA-methyltransferases (Dnmt) in acquired drug resistance of
      neuroblastoma, the present investigation was carried out to study the expression
      of Dnmtl, Dnmt3a, and Dnmt3b in drug resistant murine neuroblastoma cells, in an
      in vitro model system. We have analyzed the expression of Dnmtl, Dnmt3a, and
      Dnmt3b methyltransferases in wild type and drug resistant murine neuroblastoma
      cells by using Western blot, immunofluorescence microscopy, semiquantitative and
      quantitative real time RT-PCR analyses. The present investigation demonstrates
      that total Dnmt enzymatic activity was increased two-fold (P < 0.001) with a 33%
      increase in global DNA methylation rate in drug resistant cells. Results of the
      Western blot, immunofluorescence microscopy, RT-PCR, and quantitative real time
      RT-PCR analysis demonstrated that Dnmt1 and Dnmt3b expression increased
      significantly (P < 0.001) in drug resistant cells when compared with wild type
      cells. Dnmt3a expression did not reveal any change between wild type and drug
      resistant cells. These findings suggest that Dnmtases are differentially
      expressed in drug resistant murine neuroblastoma cells and overexpression of
      Dnmtl and Dnmt3b may contribute towards loss of function of the growth regulatory
      or tumor suppressor genes by methylation of their 'CpG' region and subsequently
      silencing of their expression. The products of these methylated genes may, thus,
      confer a high level of drug resistant phenotype in drug resistant neuroblastoma
      cells.

PMID- 12507230
TI  - Close correlation between restriction fragment length polymorphism of L-myc gene
      and susceptibility to gastric cancer.
AB  - AIM: A common inherited RFLP of the L-myc proto-oncogene has been reported to
      correlate with cancer susceptibility. Our aim was to test the hypothesis that
      there was association between L-myc S allele in gastric cancer and predisposition
      to the disease. METHODS: The distribution of L-myc polymorphism in 25 patients
      with gastric cancer was determined by polymerase chain reaction-based restriction
      fragment length polymorphism and compared with that of 83 healthy control
      subjects. RESULTS: We found a significant difference, both in the distribution of
      the LL, LS and SS genotypes and in the allelic frequencies, between the control
      group and the patient group; that is, the frequencies of L-myc alleles were, L
      and S, 0.52 and 0.48, 0.64 and 0.36, respectively. This difference was primarily
      the result of a high frequency of the S allele among gastric cancer patients
      compared to controls. There was a significant difference in the distribution of
      both genotypes (P = 0.004) and allele frequencies (P = 0.005) between patients
      with gastric cancer and control groups. CONCLUSIONS: Our results suggested that L
      myc polymorphism may be significant in an individual's susceptibility to gastric
      cancer in Turkey and may be useful for identifying patients at high risk of
      developing gastric cancer.

PMID- 12507231
TI  - Gene gun-mediated intracutaneous vaccination with papillomavirus E7 gene delays
      cancer development of papillomavirus-induced skin papillomas on rabbits.
AB  - High-risk human papillomavirus (HPV) E6 and E7 viral oncogenes are expressed in
      HPV-associated cancers, and thus represent tumor-specific antigens. We used the
      cottontail rabbit papillomavirus (CRPV) rabbit model to test whether vaccination
      with either the E6 or E7 genes alone could prevent or delay carcinoma
      development. CRPV-induced papillomas on 24 rabbits were allowed to grow for 3
      months without any treatment intervention. An immunization protocol using gene
      gun-mediated intracutaneous administration of DNA plasmids encoding the E6 or the
      E7 gene or vector only, respectively was initiated at this time point. Carcinoma
      development was followed up to 24 months after virus infection. Within this
      period, five rabbits died due to other causes but without carcinoma; one from the
      vector control group, and two each from the E6- and E7-vaccinated groups. The
      remaining seven rabbits from the vector control group developed carcinoma within
      7-17 months. The remaining six E6-vaccinated rabbits developed cancer within 8-15
      months. There was no delay in cancer development for the E6-vaccinated rabbits
      compared to the vector-injected rabbits. Some delay in cancer development in the
      remaining E7-vaccinated rabbits was observed; one developed cancer at month 23
      and a second was without cancer at month 24. In addition, some E7-vaccinated
      rabbits with primary skin carcinomas had fewer lung metastases (<2) compared to
      vector-vaccinated controls (20+). These results suggested that gene gun-mediated
      intracutaneous immunization with papillomavirus early gene E7 but not E6 delayed
      carcinoma development of papillomavirus-induced lesions.

PMID- 12507232
TI  - A novel syngeneic murine model for thoracic neuroblastoma obtained by
      intramediastinal injection of tumor cells.
AB  - In this study, a new syngeneic murine neuroblastoma (NB) model resembling stage 3
      NB with thoracic localization has been set up by intramediastinal injection of
      tumor cells. Two NB cell lines, the murine Neuro2a, and the hybrid NXS2, have
      been injected in A/J mice. In vivo tumor growth and dissemination have been
      assessed by macroscopic and microscopic histological analysis performed at
      different times post injection. Tumor cell localization and growth patterns were
      compared to those obtained by i.v. and r.p. injections. The results indicated
      that in the thoracic model both tumor cell lines grow rapidly as huge tumor
      masses but do not metastatize to distant organs. This new model may be relevant
      for testing the efficacy of novel immunotherapeutic strategies for poor prognosis
      NB patients with localized disease.

PMID- 12507233
TI  - Learning to read it right.

PMID- 12507234
TI  - Placement of palatal implants.

PMID- 12507235
TI  - Glow discharge plasma treatment of titanium plates enhances adhesion of
      osteoblast-like cells to the plates through the integrin-mediated mechanism.
AB  - PURPOSE: Initial adhesion of cells to implant surfaces and subsequent behavior of
      the cells are important determinants for biocompatibility of the implants. It was
      previously reported that both adhesion of MC3T3-E1 osteoblast-ike cells to
      titanium (Ti) plates and their differentiation into more mature cells on the
      plates were stimulated by treatment of the plates with glow discharge plasma
      (GDP). However, the mechanisms of these processes have not yet been identified.
      In this study, the adhesion and differentiation mechanism of osteoblast-like
      cells to Ti with and without GDP were investigated. MATERIALS AND METHODS: The
      adhesion and differentiation mechanism of MC3T3-E1 osteoblast-like cells to Ti,
      with and without GDP, were investigated by cultivation in serum-free medium and
      use of a competitive inhibition test to examine the influence of extracellular
      matrix proteins contained in the serum and to identify cell binding proteins. In
      addition, the amount of fibronectin adsorption on each Ti plate was investigated
      by enzyme-linked immunosorbent assay and fluorescein isothiocyanate labeling.
      Furthermore, the stress fiber formation and morphology of cells on each plate
      were evaluated microscopically. RESULTS: Adherent cells on Ti plates, with and
      without GDP, were significantly reduced in serum-free conditions and the presence
      of RGDS (Arg-Gly-Asp-Ser) peptides. Fibronectin adsorption on titanium plates was
      increased by GDP. Furthermore, stress fiber formation of cells was extremely
      progressive on the Ti plates treated with GDP and was not observed on the cells
      inhibited by RGDS peptide. DISCUSSION: These results suggest that RGDS containing
      serum proteins have a major role in regulating specific adhesion of cells to Ti,
      and GDP promoted cell adhesion and differentiation on Ti by increasing the
      adsorption of proteins. CONCLUSION: According to this study, the adhesion and
      differentiation mechanism of osteoblast-like cells to Ti, with and without GDP,
      can be obtained.

PMID- 12507236
TI  - Examination of the bone-metal interface of titanium implants coated by the
      microwave plasma chemical vapor deposition method.
AB  - PURPOSE: Diamond layers can be plated with microwave plasma chemical vapor
      deposition (MWP-CVD) treatment on metal bases such as titanium-aluminum-vanadium
      alloy (Ti-6Al-4V). The bonding strength of the diamond layer to the metal base is
      very high, so that no fissures and partial loss of coating take place-well known
      phenomena that may occur with other coatings in tribologic material testing. In
      an experimental study using 40 New Zealand White rabbits, a new method for
      coating implant material was tested for stability of the bone-metal interface.
      MATERIALS AND METHODS: The results of histomorphometric and biomechanical
      evaluation of coated and uncoated probes implanted in the distal femur of 40
      rabbits were compared. The animals were divided into 3 groups, with observation
      times of 42, 84, and 168 days. RESULTS: The bone-implant contact was 5% to 18%
      less in coated than in uncoated probes. Only the early group, with 42 days
      healing time showed significant differences. Values for the pull-off force of
      uncoated material were about 3 to 4 times higher than coated material (diamond
      layer = 2.7 microm). The force increased 2 to 3 times when 200-nm coatings were
      tested. Electron microscopy detected undercuts of the rough surface that were
      obturated by diamond when the coating was too thick. DISCUSSION: Diamond-coated
      material seems to have no corrosion problems in contrast to all other known
      implant material. CONCLUSION: An inert diamond layer on a metal base can become
      osseointegrated. Biomechanical stability increased by thinning the diamond
      coating.

PMID- 12507237
TI  - Effect of estrogen replacement and calcitonin therapies on bone around titanium
      implants placed in ovariectomized rats: a histometric study.
AB  - PURPOSE: The aim of the present study was to evaluate whether hormone replacement
      therapy (HRT) and calcitonin (CT) administration could influence bone healing
      around implants placed in ovariectomized (OVX) rats. MATERIALS AND METHODS: One
      screw-type titanium implant was placed bilaterally in OVX rats. The animals were
      assigned to one of the following groups: group 1 (n = 15), sham surgeries; group
      2 (n = 15), OVX rats; group 3 (n = 14), OVX rats administered CT 4 days/week (16
      IU/kg); group 4 (n = 14), OVX rats administered 17beta estradiol daily (20
      microg/kg). After 60 days, the animals were sacrificed and undecalcified sections
      obtained. Bone-to-implant contact (BIC) and bone area (BA) around the implants
      were determined separately for the cortical (zone A) and cancellous (zone B) bone
      areas. RESULTS: In zone A, intergroup analysis did not reveal a significant
      difference regarding BIC. In contrast, the HRT group (group 4) presented greater
      BA than groups 2 and 3 (P < .05). Data from zone B revealed that HRT eliminated
      the negative effect of the ovariectomy on BIC and BA (P < .05), while CT had no
      effect (P > .05). DISCUSSION: It was the first study to evaluate and demonstrate
      the impact of HRT and CT on bone around titanium implants in an estrogen
      deficient model. CONCLUSION: Within the limits of the present study, it may be
      concluded that HRT may prevent the influence that estrogen deficiency exerts on
      bone healing around titanium implants.

PMID- 12507238
TI  - Bacterial colonization of zirconia ceramic surfaces: an in vitro and in vivo
      study.
AB  - PURPOSE: The microbial colonization of new ceramic materials developed for
      abutment manufacturing was assessed. MATERIALS AND METHODS: The materials used in
      these experiments were disks of 'as-fired' and 'rectified' ceramic material made
      of tetragonal zirconia polycrystals stabilized with yttrium (Y-TZP) and
      commercially pure grade 2 titanium (Ti) with corresponding eluates. They were
      tested in vitro with the following bacteria: Streptococcus mutans, S. sanguis,
      Actinomyces viscosus, A. naeslundii, and Porphyromonas gingivalis. Proliferation
      was evaluated on plates by inhibitory halos around pits, previously inoculated
      with eluates obtained from the materials. Bacterial adhesion on materials was
      quantified by spectrophotometric evaluation of the slime production by the same
      bacteria. Moreover, early bacterial adhesion was evaluated in human volunteers
      and observed with SEM. RESULTS: No inhibition of bacterial proliferation using
      eluates was observed. In vitro as-fired and rectified Y-TZP showed significantly
      more adherent S. mutans than did Ti disks, while S. sanguis seemed to adhere
      easily to Ti specimens. No differences were noted for Actinomyces spp and P.
      gingivalis. In vivo Y-TZP accumulated fewer bacteria than Ti in terms of the
      total number of bacteria and presence of potential putative pathogens such as
      rods. No differences were observed between rectified and as-fired Y-TZP.
      DISCUSSION: Overall, Y-TZP accumulates fewer bacteria than Ti. CONCLUSION: Y-TZP
      may be considered as a promising material for abutment manufacturing.

PMID- 12507239
TI  - A 5-year longitudinal study of the clinical effectiveness of ITI solid-screw
      implants in the treatment of mandibular edentulism.
AB  - PURPOSE: The aim of this longitudinal study was to gain 5-year clinical
      documentation of the 1-stage surgical technique in connection with ITI solid
      screw implants used in the edentulous mandible. MATERIALS AND METHODS: One
      hundred patients with totally edentulous mandibles were treated with bar-retained
      overdentures supported by a total of 340 consecutively placed ITI solid-screw
      implants. The patients were followed at annual intervals for at least 5 years to
      evaluate implant success, longitudinal reactions of the peri-implant hard and
      soft tissues, and incidences of biologic and mechanical complications. RESULTS:
      During the trial period, a total of 4 implants failed, all prior to loading, and
      51 implants were lost to follow-up, resulting in a cumulative survival rate of
      98.8% after 5 years of functional service. The success analysis included
      additional strictly defined events (either "first occurrence of marginal bone
      loss > or = 4 mm" or "first occurrence of pocket depth > or = 4 mm" and "first
      occurrence of crevicular fluid flow rate > or = 2.5 mm) and resulted in a
      cumulative 5-year success rate of 95.7%. The median marginal bone loss
      experienced between implant placement and prosthetic treatment was 0.5 mm,
      followed by an annual bone level change of 0.1 mm for the functional period of 5
      years. The increasing incidence of remarkable plaque deposits from 19% to 50%
      represented the difficulties of the patients in maintaining a high level of oral
      hygiene, particularly for the lingual surfaces. Sulcus Bleeding Index, probing
      depth, attachment level, and crevicular fluid flow rate were used to describe the
      health of the peri-implant soft tissues and remained almost within acceptable
      standards. DISCUSSION: Survival and success rates of implants, amount of marginal
      bone loss, and periodontal indices of peri-implant soft tissues were consistent
      with those reported in the literature regarding implants with the submerged
      healing concept. CONCLUSION: With a cumulative survival rate of 98.8%, a
      cumulative success rate of 95.7%, and a median marginal bone loss of 0.5 mm
      during the healing period, followed by an annual rate of 0.1 mm after loading,
      non-submerged ITI solid-screw implants confirm the good clinical outcome of
      implant-supported treatment concepts for the rehabilitation of totally edentulous
      patients in a medium-term perspective.

PMID- 12507240
TI  - Influence of implant geometry and surface characteristics on progressive
      osseointegration.
AB  - PURPOSE: Although no currently available technique for the measurement of
      osseointegration is entirely satisfactory, 3 clinical variables can be reasonably
      associated with the process: probing depth, micromobility, and crestal bone
      height. Micromobility can be quantified to some extent with the use of the
      Periotest, a commercially available instrument In this investigation, the
      influence of surface characteristics and geometry upon Periotest value (PTV) and
      probing depth measurements was studied. MATERIALS AND METHODS: In a multicenter
      trial, 120 healthy edentulous patients received 5 or 6 implants in the anterior
      mandible and were followed for 3 years. A total of 634 implants were placed.
      Every patient received at least 1 implant of each of 3 types: threaded titanium
      plasma-sprayed (TPS), threaded hydroxyapatite-coated (HA), and cylindric HA
      coated. A randomization schedule assured that approximately equal numbers of each
      type of implant were placed and that they were uniformly distributed over the
      arch. RESULTS: Of the 4 tested combinations of dependent and independent
      variables, the only statistically significant (P < .05) effect was that of
      coating on PTV. At 1 year after prosthetic restoration, the mean PTV for HA
      coated threaded implants was -5.36 +/- 1.24, compared with -4.86 +/- 1.70 for TPS
      implants. This difference steadily declined in magnitude and significance, until,
      after 3 years, the groups were indistinguishable. DISCUSSION: This study agrees
      with the previous observations that HA coating tends to accelerate the initial
      rate of osseointegration. The absence of a difference between threaded and
      cylindric implants confirms that the PTV responds to micromobility near the
      surface, on a scale much smaller than such gross geometric features. CONCLUSION:
      On the basis of these results, one may conclude that HA-coated implants exhibit a
      more rapid decrease in micromobility than do TPS implants of identical geometry.

PMID- 12507241
TI  - The effect of smoking on achieving osseointegration of surface-modified implants:
      a clinical report.
AB  - PURPOSE: The present study evaluated the effect of smoking on achieving initial
      osseointegration when surface-modified dental implants were used. MATERIALS AND
      METHODS: During an 18-month period in a private practice setting 1,183 implants
      were placed in 461 patients. The group of smokers consisted of patients who
      smoked a half pack or more of cigarettes per day. RESULTS: The overall success
      rate for smokers and non-smokers in achieving osseointegration was 98.1%. Ninety
      seven percent of the implants placed in smokers osseointegrated successfully, and
      98.4% of implants placed in non-smokers osseointegrated successfully (P < .05).
      DISCUSSION: The surface of an implant may be a critical determinant for achieving
      osseointegration in patients who smoke. CONCLUSION: It appears from this short
      term retrospective study that smoking does not play a significant role in
      achieving the osseointegration of surface-modified dental implants.

PMID- 12507242
TI  - A prospective multicenter evaluation of 1,583 3i implants: 1- to 5-year data.
AB  - PURPOSE: The purpose of this prospective multicenter study was to evaluate the
      efficacy of 3i threaded implants for the treatment of edentulous patients in a 1-
      to 5-year period. This article reports the total data and global results of 3
      threaded designs of 3i implants: self-tapping, ICE, and Osseotite. MATERIALS AND
      METHODS: A total of 1,583 implants (619 ICE, 545 Osseotite, and 419 self-tapping)
      were placed between 1995 and 1999 in 528 patients at 13 European clinical
      centers. The average age of the patients was 53.6 years. Clinical and
      radiographic evaluations were performed annually for up to 5 years. RESULTS: Of
      the total implants, 707 were placed in the maxilla and 876 in the mandible. A
      total of 1,162 implants were placed in posterior segments. Forty-eight implants
      were lost to follow-up and 55 were failures. The most frequent prosthetic
      indication was the short-span fixed prosthesis (440 cases), followed by 172
      single-tooth replacements, 56 long-span prostheses, and 4 overdentures.
      Radiographic evaluation after 6, 12, and 24 months of implant loading showed,
      respectively, mean crestal bone loss of 0.04 +/- 1.3 mm, 0.12 +/- 1.6 mm, and 0.2
      +/- 1.7 mm. A cumulative survival rate of 96.5% was observed 5 years after
      implant placement, with 97.2% survival in the maxilla and 95.8% in the mandible.
      The survival rate was similar in anterior (96.7%) and posterior (96.5%) segments.
      DISCUSSION: A total of 55 failures were reported in this study with 47 early
      failures and 8 late failures. The rate of late failures is of utmost importance
      for the restorative dentist. CONCLUSION: This clinical study gives evidence of
      very high success rates using 3 threaded designs of 3i implants.

PMID- 12507243
TI  - Microbiota around root-form endosseous implants: a review of the literature.
AB  - Although high success rates for root-form endosseous implants have been reported,
      failures occasionally occur, and these implants must be removed. At least 10% of
      the failures have been suggested to be the result of peri-implantitis. There is
      some evidence that periodontal pathogens, mainly those belonging to the group of
      gram-negative anaerobic rods, play a role in the etiology of peri-implantitis.
      This article provides an overview of the literature associated with common peri
      implant microbiology and an assessment as to whether bacteria associated with
      periodontitis exert a possible risk for peri-implant tissue breakdown. The peri
      implant area is colonized by a large variety of oral microbial complexes. The
      microflora of the oral cavity prior to implant placement determines the
      composition of the microflora in the peri-implant area. Implants involved in peri
      implantitis are colonized with large amounts of gram-negative anaerobic bacteria,
      including Fusobacteria, spirochetes, Bacteroides forsythus, and "black-pigmented
      bacteria" such as Prevotella intermedia, Prevotella nigrescens, and Porphyromonas
      gingivalis. Also, Actinobacillus actinomycetemcomitans can be isolated from these
      lesions. Thus, the microflora of peri-implantitis lesions resembles that of adult
      or refractory periodontitis. However, the presence of periodontal pathogens does
      not always lead to a destructive process. Therefore, the etiologic role of
      specific microorganisms in implant failure related to infection is still not
      resolved. Controversy remains as to whether organisms recovered from the original
      microflora cause the failure (and if so to what extent) or merely result from the
      infection. Nevertheless, there is accumulating evidence that bacteria cause the
      disease, while the individual's genetic makeup and environmental influences
      determine the severity of the disease.

PMID- 12507244
TI  - Removal torque of immediately loaded transitional endosseous implants in human
      subjects.
AB  - PURPOSE: Transitional implants were designed to support provisional restorations
      and to allow for load-free osseointegration of conventional implants while a
      patient was provided with immediate esthetics and function. The purpose of this
      study was to evaluate the removal torque values of immediately loaded
      transitional implants in human subjects. MATERIALS AND METHODS: Thirty-one 1.8-mm
      diameter transitional implants were placed in 4 patients to support provisional
      restorations and were subjected to immediate loading. Removal torque values were
      recorded using a modified ITI torque driver, which was calibrated on an Instron
      test machine. Torque values were subjected to analysis of variance and post hoc
      comparisons of means (P < .05). RESULTS: Twenty-six implants were removed intact
      with torque values between 10.5 and 22.9 Ncm, while 5 fractured at the bone crest
      at values between 27.1 and 35.4 Ncm. Mean torque values increased with time in
      function. These values were significantly lower in the maxilla (16.1 +/- 4.8 Ncm)
      than in the mandible (24.0 +/- 7.3 Ncm). DISCUSSION: Results suggest that these
      transitional implants may be safely removed from the maxilla after 7 to 15
      months, but there is a risk of implant fracture during removal from the mandible
      after 10 months. CONCLUSION: Removal torque levels for these implants indicate
      varying degrees of integration even though they were subjected to immediate
      loading.

PMID- 12507245
TI  - Endosseous implants in horizontal alveolar ridge distraction osteogenesis.
AB  - PURPOSE: This study evaluated horizontal distraction of the narrow alveolar ridge
      in dogs and the possibility of achieving osseointegration of implants placed into
      the distracted site during a consolidation period. MATERIALS AND METHODS: Six
      beagle dogs weighing approximately 9 to 10 kg were used in this experiment.
      Twelve weeks after extraction of the mandibular premolars, horizontal alveolar
      ridge distraction was performed using an originally designed lengthening
      apparatus. Twelve days after the completion of distraction, screw-type implants
      were placed into the distracted site. RESULTS: Twelve weeks after the placement
      of implants, thin lamellar bone rose horizontally from the transport segment
      toward the surface of the implant. Twenty-four weeks after their placement, the
      implants were fully embedded in mature lamellar bone, and direct bone contact
      with the implant surface could be seen. DISCUSSION: Horizontal alveolar ridge
      distraction was performed successfully by using a lengthening apparatus in the
      narrow alveolar models. Osseointegration was achieved even though the implants
      were placed into the distracted site during the consolidation period. CONCLUSION:
      Horizontal alveolar ridge distraction can be a beneficial technique in the
      placement of implants In the narrow alveolar ridge in the dog population.

PMID- 12507246
TI  - Maxillary sinus septa: a 3-dimensional computerized tomographic scan analysis.
AB  - PURPOSE: The purpose of this study was to determine the prevalence, size,
      location, and morphology of maxillary sinus septa in dentate, partially dentate,
      and edentulous maxillae. MATERIALS AND METHODS: Data from 312 sinuses were
      analyzed from reformatted computerized tomograms utilizing SIM/Plant software.
      The sample consisted of 156 patients (106 women and 50 men, with ages ranging
      between 24 and 86 years and a mean age of 55.4 years) who were being treatment
      planned to receive implant-supported restorations. RESULTS: A total of 75 septa
      were found in 312 maxillary sinuses (24%), which corresponded to 32.7% of the
      patients (51 of 156). Completely edentulous patients presented with 33.3% of the
      total septa, while 66.7% of the septa were identified in partially edentulous
      patients. Analysis of the anatomic location of the septa within the sinus
      revealed that 18 (24.0%) septa were located in the anterior region, 31 (41.0%)
      were in the middle, and 26 (35.0%) were in the posterior region. Measurements of
      height of the septa varied among different areas. The lateral area ranged from 0
      to 15.7 mm (with a mean of 3.54 +/- 3.35 mm), the middle area ranged from 0 to
      17.3 mm (with a mean of 5.89 +/- 3.14 mm), and the medial area ranged from 0 to
      20.6 mm (with a mean of 7.59 +/- 3.76 mm). A total of 20 septa (26.7%) were
      located in the immediate apical region of teeth. The remaining 55 septa (73.3%)
      were related to edentulous areas. DISCUSSION: Septa may arise in any of the 3
      regions of the maxillary sinus irrespective of the degree of dentulism or
      edentulism present. CONCLUSION: To avoid unnecessary complications during sinus
      augmentation procedures, adequate and timely identification of the anatomic
      structures inherent to the maxillary sinus are required.

PMID- 12507247
TI  - The zygomatic implant: preliminary data on treatment of severely resorbed
      maxillae. A clinical report.
AB  - The Branemark Zygomaticus implant was used in conjunction with premaxillary
      standard implants for the reconstruction of resorbed edentulous maxillae. A total
      of 44 zygomatic implants and 80 premaxillary implants were placed in 22 patients.
      All implants were stabilized at phase II surgery using a rigid bar. After soft
      tissues had healed, implant-supported fixed prostheses were fabricated. This
      article presents a preliminary report on 22 patients followed for 34 months, with
      a 100% success rate for the zygomatic implants and a 91.25% success rate for the
      premaxillary implants.

PMID- 12507248
TI  - Development of gingival esthetics in the edentulous patient prior to dental
      implant placement using a flangeless removable prosthesis: a case report.
AB  - Development of gingival contours found in healthy natural dentitions enhances the
      esthetic results achieved with implant-supported fixed prostheses. However, this
      endeavor is frequently difficult to achieve, especially in the completely
      edentulous patient. Edentulous patients with optimal hard and soft tissue can be
      treated with a specially designed removable prosthesis that will develop gingival
      contours prior to implant placement. By means of a transitional complete
      removable prosthesis with ovate pontics and no labial flange, a natural-looking
      soft tissue profile can be developed prior to dental implant placement. A
      minimally invasive tissue punch surgical technique is used to place the implants,
      which are immediately restored with a 1-piece, cross-arch, provisional fixed
      prosthesis. This article presents the prosthodontic and surgical protocols
      utilized to improve the appearance of the definitive implant rehabilitation.

PMID- 12507249
TI  - Restoration of the atrophied posterior mandible with transverse alveolar
      maxillary/mandibular implants: technical note and case report.
AB  - Restoration of the atrophied posterior mandibular alveolus has been a surgical
      challenge in the past. Many treatment options have been published, each with
      unique shortcomings. This study will review and compare these techniques to a new
      type of implant, the transverse alveolar maxillary/mandibular implant (TAMMI).
      Using modified Nobel Biocare Branemark System zygomatic implants that were
      shortened to 11.5, 13, 15, 18, 20, 22.5, or 25 mm, the authors reconstructed
      atrophied posterior mandibles. These TAMMIs were placed at a 45-degree angle,
      engaging both the crest of the ridge and the buccal cortex. Using TAMMIs,
      atrophied posterior mandibular alveoli as small as 9 mm have been successfully
      restored without complication to the inferior alveolar nerve.

PMID- 12507250
TI  - For your patients receiving endosseous implants for immediate loading, how are
      the implant-supported crowns or prostheses initially put into occlusal function,
      and what instructions are given for their use?

PMID- 12507251
TI  - Effect of meso-2,3-dimercaptosuccinic acid on urinary lead excretion in exposed
      men.
AB  - The efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) was evaluated in workers
      occupationally exposed to lead (Pb; blood level >50 microg/dL). Ten men were
      given 600 mg of DMSA per orem daily, for five days. Pb concentrations of whole
      blood and urine were determined throughout therapy. Hematology analyses, blood
      chemistry, and urinalysis were obtained at the start of the study, at the end of
      the DMSA treatment, and at 72 hours after the administration of the final dose.
      DMSA therapy had no influence on hepatic, hematologic, or renal functions and was
      effective in decreasing the concentration of blood Pb in all the subjects without
      adverse drug reactions.

PMID- 12507252
TI  - Traditional medicine poisoning in Zimbabwe: clinical presentation and management
      in adults.
AB  - Traditional medicines (TMs) have been reported as major causes of hospital
      admissions in some African countries including Zimbabwe. There is, however, still
      a paucity of information with regards to their clinical presentations. We carried
      out a retrospective case series of all cases of traditional medicine poisoning
      (TMP) at eight main referral hospitals in Zimbabwe January 1998-December 1999
      inclusive) to describe the most common signs and symptoms, reasons for, and
      management of TMP in adults. Where the reasons for taking the TM were known, most
      cases had taken the medicine for either abdominal pains or aphrodisiac purposes.
      Nonspecific adverse effects including vomiting, abdominal pains, and diarrhoea
      were the most commonly encountered. A large proportion of patients with TMP also
      suffered from genito-urinary tract adverse outcomes especially haematuria and
      dysuria. Intravenous fluids were the most commonly employed therapeutic modality
      for TMP, probably in an effort to dilute or increase excretion of the toxins.
      Further research is required to elucidate the toxic components responsible for
      the observed ill effects and whether these effects are due to the medicines
      themselves or to co-existing illnesses.

PMID- 12507253
TI  - The toxicity of exposure to the organochlorine, dieldrin, at a sympathetic
      junction and on the skin of the frog, Caudiverbera caudiverbera.
AB  - The effects of the organochlorine, dieldrin, were tested on a noradrenergic
      synapse of the frog, Caudiverbera caudiverbera. Nerve stimulation induced a
      transient increase in short circuit current (SCC) and in the potential difference
      (PD), which consisted of a rapid and then a slow component. Dieldrin in the
      concentration range 0.01-1.0 mM caused a concentration-dependent block of both
      components to 32% of their control values, which was partially reversed by
      washout. In some experiments, this blocking effect was preceded by an initial
      increase in the magnitude of the electrical parameters of the nonstimulated skin
      and also in the synaptic response to stimulation when the lowest dieldrin
      concentration (0.01 mM) was applied; higher concentrations (0.1-1.0 mM) led to
      progressive reduction of the responses. Results are interpreted as a perturbation
      of the lipid bilayer structure, which affects the functionality of lipid-protein
      complexes, leading, on one hand, to glandular Cl- channel inactivation and
      epithelial Na+ channel blockade and, on the other hand, to transient glandular Cl
      activation, opening of a putative Na+ channel, and subsequent blockade.

PMID- 12507254
TI  - Steroidogenic alterations in testes and sera of rats exposed to formulated
      Fenvalerate by inhalation.
AB  - Fenvalerate (Fen) is a synthetic pyrethroid, which is commonly used for
      destroying a variety of insect pests damaging several vegetable, fruit, and
      cotton crops. This insecticide is also used to mitigate household insects like
      flies, cockroaches, mosquitoes, and so forth. Human beings are exposed to
      formulated Fen preparations mostly by inhalation during spraying in fields for
      crop protection, for control of household insects, and also during handling and
      packaging at manufacturing plants. Limited online information is available
      regarding toxic effects of formulated Fen exposure on mammalian reproductive
      system. The present study has been undertaken to investigate male reproductive
      toxic effects of a formulated preparation of Fen (20% EC) particularly in
      relation to steroidogenic alterations in testes and sera of rats exposed by nose
      only inhalation for (4 hours/day and five days a week) for three months. The
      results indicate significant reduction in the weight of testes, epididymal sperm
      counts, and sperm motility, along with decrease in marker testicular enzymes for
      testosterone biosynthesis viz. 17-beta-hydroxy steroid dehydrogenase (17-beta
      HSD) and glucose-6-phosphate dehydrogenase (G6PDH), leading to net decrease in
      serum testosterone concentration in group of rats exposed to one-fifth LC50 of
      Fen (20% EC) by inhalation (4 hours/day, five days a week) subchronically for
      three months. These results for the first time indicate the role of testosterone
      in Fen (20% EC)-induced male reproductive toxicity of rats subchronically exposed
      by inhalation probably due to neuroendocrine-mediated phenomenon and hormone
      disrupting property of the insecticide.

PMID- 12507255
TI  - Flunitrazepam variably alters morphine, buprenorphine, and methadone lethality in
      the rat.
AB  - Opiates and substitution products are frequently abused, alone and in association
      with benzodiazepines. While this combination may result in severe respiratory
      depression and death, the quantitative relationship remains uncertain. We
      performed randomized, blinded intravenous median lethal dose (MLD) studies in
      Sprague-Dawley rats of morphine, buprenorphine, and methadone, alone and in
      combination with intraperitoneal flunitrazepam pretreatment. We employed the up
      and-down method, performed in quadruplicate, comparing time to death following
      opioid injection. Results are expressed as median of four series (extremes). The
      MLDs of morphine, buprenorphine, and methadone alone were 64.0 (33.6:79.5), 234.6
      (168.6:284.4), and 22.5 (19.3:24.1) mg/kg, respectively, and 60.6 (35.2:88.2),
      38.4 (30.6:54.0), and 13.0 (9.7:13.8) mg/kg, respectively, after pretreatment
      with 40 mg/kg flunitrazepam. Times to death for morphine, buprenorphine, and
      methadone alone were 2.5 (0.8:24), 0.02 (0.0:24), and 2.0 (0.0:24) hours,
      respectively, and 13.5 (0.0:144), 24.0 (0.0:120), and 0.0 (0.0:24) hours,
      respectively, after pretreatment with flunitrazepam 40 mg/kg, ip. Flunitrazepam
      significantly altered methadone (P=0.02) and buprenorphine (P=0.02) but not
      morphine lethality (P=0.77). Flunitrazepam significantly prolonged time to death
      only for buprenorphine (P<0.01). Flunitrazepam-opioid drug-drug interactions are
      more complex than is generally believed. Mechanistic studies of flunitrazepam
      opioid lethal interactions are needed.

PMID- 12507256
TI  - Modification of doxorubicin-induced cardiotoxicity: manipulation of the dosage
      schedule.
AB  - Modification of the dosing schedule for doxorubicin (DOX) administration
      represents a possible method of reducing cardiotoxicity from this potent anti
      cancer drug, while at the same time maintaining its cytotoxic action. The
      quantitative effects of modified dosage scheduling have been investigated in a
      clinically relevant rat model. Cardiotoxicity to DOX was assessed by the degree
      of reduction in cardiac output at 4-24 weeks after the intravenous administration
      of DOX. The effects of dose schedules involving three or six small dose
      administrations, over one and two weeks, were compared with that produced by
      large single doses of DOX. The total drug dose administered for each schedule was
      varied in order to establish dose-effect relationships. After a total dose of 3
      mg/kg DOX, given as three or six equal small doses, there was a gradual decline
      in cardiac output in the first 12 weeks after drug administration. Between 12 and
      24 weeks, the reduction in cardiac function was relatively stable at between 65%
      and 85% of that of age-matched controls for three and six equal small doses,
      respectively. Dose-effect curves for animals showing a > or = 30% reduction in
      cardiac function after 12 weeks indicated the degree of reduction in cardiac
      function produced by the modified dose scheduling. Compared with a large single
      dose, larger total doses were required to produce the same severity of damage.
      Thus, schedules based on three and six equal small doses resulted in dose
      modification factor of 1.5 +/- 0.23 and 2.1 +/- 0.28, respectively, when compared
      with the same effect produced by a large single dose. This appeared to be
      independent of the severity of cardiac damage, suggesting a simple mathematical
      relationship between the total acceptable dose of DOX and the dose administered
      at each intravenous injection. These modifications in the cardiotoxicity of DOX
      produced by the administration of multiple small doses were of the same order of
      magnitude as that produced by other methods introduced to reduce anthracycline
      cardiotoxicity.

PMID- 12507257
TI  - The influence of simultaneous whole body exposure to cigarette smoke and low
      protein diet feeding on fertility, reproduction, and progeny of rats.
AB  - The aim of the present study was to evaluate the toxicological influence of
      different concentrations of tobacco smoke and low-protein diet on fertility,
      reproduction, and survival of offspring of Wistar female rats. We studied three
      generations, two litters in each. There were 192 animals in parent generation.
      Animals were exposed to three different concentrations of tobacco smoke that were
      reflected by the carbon monoxide (CO) concentration (500, 1000, and 1500 mg CO/m3
      air) during 11 weeks (six before and two weeks during mating, and three weeks of
      pregnancy). Additionally, animals were divided into two subgroups that were fed
      normal or low-protein diet. In the present study, we concentrated on the indices
      describing the reproduction ability, fertility, and rearing of pups of mothers
      exposed to tobacco smoke. The parameters of newborns survival were estimated
      also. We concluded that neither tobacco smoke exposure nor the low-protein diet
      changed the duration of pregnancy. The tobacco smoke in all doses and low-protein
      diet had a negative influence on fertility, reproduction, and survival of
      newborns from exposed mothers. This influence was mainly attributed to the
      tobacco smoke exposure. The levels of carboxyhaemoglobin were increasing with
      increasing tobacco smoke concentration.

PMID- 12507258
TI  - Fatal overdosage with sildenafil citrate (Viagra): first report and review of the
      literature.
AB  - A fatal case of sildenafil citrate (Viagra) overdosage is presented. The deceased
      was a 56-year old male found dead at home, with a past history of diabetes
      mellitus, hypertension, chronic alcoholism, anxio-depressive disorders, and
      erectile dysfunction. The main autopsy findings were cardiomegaly (650 g) with
      dilated cardiomyopathy, diffuse coronary atherosclerosis with no sign of acute
      ischaemic disease, and extensive fibrosis of the myocardium, especially affecting
      the cardiac conducting tissue. As measured by HPLC/MS, sildenafil concentration
      in postrmortem blood (6.27 microg/mL) exceeded at least four times the highest
      therapeutic levels previously reported. The results are discussed in the light of
      the literature about the cardiovascular side effects of sildenafil, with special
      emphasis on the recently evidenced arrhythmogenic potential of the drug. This is
      the first report of a fatality caused by sildenafil overdosage.

PMID- 12507259
TI  - A dynamic problem to knowledge linking Semantic Web service based on clinical
      codes.
AB  - Many information needs arise during everyday clinical practice. Problem to
      knowledge linking aims to answer these needs by providing contextually
      appropriate medical knowledge in the right place and at the right time. Empirical
      evidence shows that well-informed physicians and patients are able to make better
      clinical decisions that positively affect healthcare outcomes. This paper reports
      on the design and development of a re-usable and flexible Semantic Web problem to
      knowledge linking service. The service makes use of metadata and clinical codes
      contextually to link disparate Electronic Patient Record clients to resources in
      an online medical knowledge service (HealthCyberMap). Clinical codes act as crisp
      knowledge hooks, providing a reliable common backbone language for communication
      between Electronic Patient Records and HealthCyberMap. Ideas to improve the
      service are also discussed. By minimizing irrelevant leads (noise) and reducing
      the time needed to find relevant information (the right contextually relevant
      knowledge is linked to real patient data in the Electronic Patient Record), the
      system is potentially beneficial. The actual success of the system will depend on
      the quality and granularity of metadata it uses and the topical coverage and
      quality of resources to which it points.

PMID- 12507260
TI  - Towards personalized Internet health information: the STEPPS architecture.
AB  - PRIMARY OBJECTIVE: STEPPS (STructured Evaluated Personalized Patient Support)
      proposes a strategy for integration of electronic patient records with Internet
      health-related content and its consequent use in personalized information
      retrieval for patient education. The application domain is the post-discharge
      support of burn patients in the Netherlands. MATERIALS AND METHODS: We developed
      an electronic patient record interface for structured data collection in burn
      care. The system's thesaurus was projected to UMLS terms and the corresponding
      codes were incorporated in our software. A list of topics central to burn patient
      education was identified and a collection of related Web pages was compiled using
      meta-search software (Copernic2001Pro). The HTML pages were filed into catalogues
      by the Collexis indexing-matching software, using the UMLS Metathesaurus as
      indexing vocabulary. RESULTS: The bilingual (English and Dutch) structured data
      interface is currently used to create a database of retrospective patient data.
      Each patient's profile, i.e. set of characteristics employed to personalize
      information retrieval, can be automatically extracted. We have assembled a
      collection of more than 2500 Internet pages containing relevant information for
      burn patients. When patient data is available, the Collexis matching engine will
      accept the patient's profile as input and retrieve the most relevant HTML
      documents available in the catalogues. DISCUSSION: We have addressed some basic
      issues around the technical feasibility of linking electronic patient record data
      to online content. Although the functionality of STEPPS is not yet optimal, it
      contributes to the efforts towards improved relevance of information retrieval.
      Electronic patient record applications in conjunction with Internet resources can
      give a significant boost to the availability of tailored health education
      material. In this context, quality assurance of online health information is an
      indispensable element.

PMID- 12507261
TI  - Health websites in Italy: use, classification and international policy.
AB  - In this paper, we discuss international policy in relation to the use of health
      websites and we describe the results obtained from application of a search engine
      to the recognition and classification of health websites in Italy. We then
      compare the results with health websites in other countries. Effective use of
      technology has led to medical advances that have not only extended life
      expectancy, but also fuelled an increasingly well-informed public to expect more
      and more from today's healthcare providers. As a consequence of the Web's rapid,
      chaotic growth, the resulting network of information lacks organization and
      structure and the quest for a method of quickly finding relevant and reliable
      information is spawning the growth of Internet portal sites. The US and the
      European Union and now Italy, have established the importance of rules to check
      the quality of health sites both for the non-professional users (citizens),
      mainly for privacy and security (for example, of medical records); and for health
      operators (physicians and others), where the most important thing is to evaluate
      the quality of content. In June 2001, the search engine used here found 2627
      Italian health sites, of which only 46 exhibited the HON Code, and they can be
      classified into: 1% personal medical sites, 17% health portals, 18%, metasites,
      27% documental sites and 37% information sites for health operators and/or for
      citizens.

PMID- 12507262
TI  - Enhanced care of hypertensive patients using the Internet.
AB  - BACKGROUND: Medical guidelines provide recommendations that ought to help
      physicians in medical decision-making under different circumstances. To develop
      electronic medical guidelines and to make them available for physicians using the
      Internet can further enhance the quality and efficiency of health care,
      especially with the simultaneous use of electronic health records. OBJECTIVES:
      This study aims to outline the needs for web-based systems that support the use
      of medical guidelines in practice; and to focus on the development of web-based
      electronic medical guidelines for treatment of arterial hypertension. METHODS:
      The importance of electronic health record in cardiology for data acquisition,
      data storage and data mining is considered. The anonymized database of
      approximately 1800 hypertensive patients has been created to compare medical
      practice with guidelines and discover features of diseases that can help with
      their management. Using this database we evaluated several web-based electronic
      guidelines systems. RESULTS: The 1999 WHO/ISH Guidelines for the Management of
      Hypertension were formalized and interpreted using the Guide-X methodology, using
      the Apollo system and web-based electronic guidelines. The web-based electronic
      guidelines were tested on the smaller anonymous recent data set of 840
      hypertensive patients. CONCLUSIONS: An easy transfer of knowledge from medical
      guidelines to structured electronic guidelines opens new possibilities for easy
      reusability of medical knowledge by general practitioners and clinicians.

PMID- 12507263
TI  - Security of medical multimedia.
AB  - The application of information technology to health care has generated growing
      concern about the privacy and security of medical information. Furthermore, data
      and communication security requirements in the field of multimedia are higher. In
      this paper we describe firstly the most important security requirements that must
      be fulfilled by multimedia medical data, and the security measures used to
      satisfy these requirements. These security measures are based mainly on modern
      cryptographic and watermarking mechanisms as well as on security infrastructures.
      The objective of our work is to complete this picture, exploiting the
      capabilities of multimedia medical data to define and implement an authorization
      model for regulating access to the data. In this paper we describe an extended
      role-based access control model by considering, within the specification of the
      role-permission relationship phase, the constraints that must be satisfied in
      order for the holders of the permission to use those permissions. The use of
      constraints allows role-based access control to be tailored to specifiy very fine
      grained and flexible content-, context- and time-based access control policies.
      Other restrictions, such as role entry restriction also can be captured. Finally,
      the description of system architecture for a secure DBMS is presented.

PMID- 12507264
TI  - Implementing context and team based access control in healthcare intranets.
AB  - The establishment of an efficient access control system in healthcare intranets
      is a critical security issue directly related to the protection of patients'
      privacy. Our C-TMAC (Context and Team-based Access Control) model is an active
      security access control model that layers dynamic access control concepts on top
      of RBAC (Role-based) and TMAC (Team-based) access control models. It also extends
      them in the sense that contextual information concerning collaborative activities
      is associated with teams of users and user permissions are dynamically filtered
      during runtime. These features of C-TMAC meet the specific security requirements
      of healthcare applications. In this paper, an experimental implementation of the
      C-TMAC model is described. More specifically, we present the operational
      architecture of the system that is used to implement C-TMAC security components
      in a healthcare intranet. Based on the technological platform of an Oracle Data
      Base Management System and Application Server, the application logic is coded
      with stored PL/SQL procedures that include Dynamic SQL routines for runtime value
      binding purposes. The resulting active security system adapts to current need-to
      know requirements of users during runtime and provides fine-grained permission
      granularity. Apart from identity certificates for authentication, it uses
      attribute certificates for communicating critical security metadata, such as role
      membership and team participation of users.

PMID- 12507265
TI  - Construction of a system for the access, storage and exploitation of data and
      medical images generated in radiology information systems (RIS).
AB  - We present the analysis, design and implementation of a system that allows
      specialists at a medical centre to recuperate and manage information produced by
      computers that generate medical diagnosis images. The main objective of the
      system is to define an architecture that provides doctors with an easy and
      centralized access to any information they may need, and to allow users to access
      this information from the computers at the hospital itself as well as from remote
      locations, which then require telemedicine sessions. The architecture is built
      according to a layered and modular methodology, which provides high scalability
      and interoperability with other information systems (HIS, RIS, etc). All the
      information is stored in a database: not only the various image studies of the
      patient, but also all data concerning the diagnosis and any comments the
      specialist may have made. We have also incorporated tools that are not usually
      found in conventional systems (image segmentation, advanced visualization, etc),
      but that help the specialist with the decision-making process.

PMID- 12507266
TI  - Wireless and Web-based medical monitoring in the home.
AB  - A remote medical monitoring system is described, which continuously monitors
      patients' state of health. The system uses the services provided by intranets and
      the Internet to allow remote supervision of patients, who may be domiciled in
      their own home. A hardware/software prototype system has been constructed to
      demonstrate the use of non-invasive and minimally intrusive sensors attached to
      patients. Continuous real-time data is acquired, stored and processed. A wireless
      system or wires connect these monitor devices to the World Wide Web and, on
      request, information is delivered to authorized medical staff via a web browser
      or Wireless Application Protocol-enabled mobile telephones. Medical staff may
      examine real-time data or graphical information and make comparisons with
      historical data. Parameters may be set to select and control the data acquisition
      devices. The potential exists for augmentation of patient health by development
      of novel sensors and low-power electronic circuitry, and this research continues.

PMID- 12507267
TI  - Hip-Op: an innovative software to plan total hip replacement surgery.
AB  - This paper describes an innovative surgical simulation software environment for
      the pre-operative planning of total hip replacement surgery. The software is a CT
      based three-dimensional planning environment, with a user-friendly graphic user
      interface based on the multimodal display visualization paradigm. Although it
      relies on a fully three dimensional internal representation, this approach
      represents the relevant anatomical objects by means of multiple views, each
      simulating a different medical imaging modality familiar to the medical
      professional. In the Hip-Op program the multimodal display interface integrates
      four different display modalities: orthogonal radiographs, Blended slices, CT
      slices, and arbitrary slices. A conventional surface rendering view is also
      available. The user 'navigates' the prosthetic components, which are dynamically
      selected from a library of available parts, within the CT volume while the
      implant and the patient anatomy are simultaneously rendered in each specialized
      view. Beside a consideration of anatomical compatibility, the surgeon may
      evaluate the planned implant type, size and position, also on the basis of two
      analysis modules that compute the achieved level of implant fitting and filling.
      After being evaluated in an internal clinical trial, the software is currently
      made available as freeware at http:// www.ior.it/hipop/.

PMID- 12507268
TI  - Management of data from clinical trials using the ArchiMed system.
AB  - Clinical trials constitute a key source of medical research and are therefore
      conducted on a regular basis at university hospitals. The professional execution
      of trials requires, among other things, a repertoire of tools that support
      efficient data management. Tasks that are essential for efficient data management
      in clinical trials include the following: the design of the trial database, the
      design of electronic case report forms, recruiting patients, collection of data,
      and statistical analysis. The present article reports the manner in which these
      tasks are supported by the ArchiMed system at the University of Vienna and Graz
      Medical Schools. ArchiMed is customized for clinical end users, allowing them to
      autonomously manage their clinical trials without having to consult computer
      experts. An evaluation of the ArchiMed system in 12 trials recently conducted at
      the University of Vienna Medical School shows that the individual system
      functions can be usefully applied for data management in clinical trials.

PMID- 12507269
TI  - Using the Web to aid biochemists and microbiologists: an example of computer
      based learning using PCR as an example.
AB  - The aim of this study was two-fold: to make available to the medical community a
      fast, efficient tool for troubleshooting PCR problems, and to demonstrate that
      hypermedia allow one to approach this kind of problem in a new, more useful way.
      The Web provides access to an enormous amount of information in the medical area,
      and in particular enables troubleshooting of new techniques in the medical
      laboratory. Currently it is possible to find textual information but it is not
      always easy to find hypermedia information. In many cases authors change only the
      means of dissemination of a book or paper to the Web, but do not adapt the
      information to the features of this new medium. The prototype of our hypermedia
      application was developed using Director and Flash programs (Macromedia), the
      application was developed from a decision tree built as a result of information
      compiled from expert PCR users and the existing literature. It was implemented on
      a website using Dreamweaver (Macromedia). The usefulness and possibilities of
      this application have been tested with physicians, medical laboratory
      technicians, and health science students, and have been proven to be more
      effective than traditional methods, both in education processes and in helping
      researchers and medical laboratory technicians in their daily work. The advance
      and popularization of the Internet in the medical profession requires information
      on the Web to adapt to the advantages offered by hypermedia. This new step must
      be taken, and the Web must offer medical users not only a different medium of
      information distribution but also a new way of handling and obtaining
      information.

PMID- 12507270
TI  - A computer-based diagnostic and prognostic system for assessing urinary bladder
      tumour grade and predicting cancer recurrence.
AB  - PURPOSE: A computer-based system was designed, incorporating subjective criteria
      employed by pathologists in their usual microscopic observation of tissue samples
      and measurements of nuclear characteristics, with the purpose of automatically
      assessing urinary bladder tumour grade and predicting cancer recurrence. MATERIAL
      AND METHODS: Ninety-two cases with urine bladder carcinoma were diagnosed and
      followed-up. Forty-seven patients had cancer recurrence. Each case was
      represented by eight histological (subjective) features, evaluated by
      pathologists, and thirty-six automatically extracted nuclear features. Grading
      and prognosis were performed by neural-network based classifiers employing both
      histological and nuclear features. RESULTS: Employing a combination of
      histological and nuclear features, highest classification accuracy was 82%,
      80.5%, and 93.1% for tumours of grade I, II and III respectively. The prognostic
      system, gave a significant prognostic assessment of 72.8% with a confidence of
      74.5% that cancer might recur and of 71.1% that might not, employing two
      histological features and two textural nuclear features. CONCLUSIONS: The system
      for grading and predicting tumour recurrence may serve as a second opinion tool
      and features employed for designing the system may be of value to pathologists
      using descriptive grading systems.

PMID- 12507271
TI  - Perioperative hyperglycemia is a strong correlate of postoperative infection in
      type II diabetic patients after coronary artery bypass grafting.
AB  - This study was planned to assess the relationship of perioperative glycemic
      control to the subsequent risk of infectious complications and to compare early
      clinical outcomes of coronary artery bypass surgery in diabetics with
      nondiabetics in a single center. A total of 1090 adults who underwent coronary
      artery surgery in a five year period were included in a retrospective cohort
      study based on available chart review. Of 1090 patients, 400 had type II diabetes
      mellitus. Intraoperative and postoperative blood glucose levels in diabetic group
      were manipulated by means of a continuous insulin infusion. Data of pre- and
      postoperative blood glucose levels were evaluated with respect to postoperative
      infection risk for diabetics. Risks of early mortality, cerebrovascular accident,
      and postoperative infection in diabetic patients were compared with the
      nondiabetic group. High preoperative mean glucose levels were the main risk
      factor for the development of postoperative infection (p = 0.012 and p = 0.028
      for the mean glucose levels 1 and 2 days before operation, respectively). For
      diabetic group, of 400 patients 20 (5%) were diagnosed to have postoperative
      infection (superficial sternal wound in 3 (0.75%), donor site infection in 4
      (1%), mediastinitis in 5 (1.25%), urinary tract infection in 6 (1.5%), and lung
      infection in 2 (0.5%) patients). The diabetic group had significantly higher
      prevalence of mediastinitis, donor site infection, urinary tract infection and
      total infection (p values were 0.048, 0.013, 0.009, and 0.044, respectively).
      Early mortality was higher among diabetics than in nondiabetics (1.73% vs 3%, p =
      0.048) but the risk of cerebrovascular accident in diabetics was not greater than
      in nondiabetics in early period. In patients with diabetes who undergo coronary
      artery bypass surgery, preoperative hyperglycemia is an independent predictor of
      short-term infectious complications and total length of stay in hospital.

PMID- 12507272
TI  - Progesterone metabolism in human leukemic monoblast U937 cells.
AB  - Progesterone markedly inhibits the functions of human macrophages and T
      lymphocytes, and acts as an immunosuppressant during pregnancy. It is important
      to examine progesterone metabolites to understand the overall bioactive
      properties of this sex steroid. However, progesterone metabolism has not been
      examined in human immune cells. The human leukemic monoblast U937 cell line
      exhibits monocytic lineage and provides a valuable model to analyze monocyte
      macrophage differentiation. Therefore, in this study, we analyzed progesterone
      metabolism in U937 cells by thin-layer chromatography. Progesterone was
      metabolized to 5alpha-pregnan-3beta,6alpha-diol-20-one via 5alpha
      dihydroprogesterone and 5alpha-pregnan-3beta-ol-20-one, and 5alpha-pregnan
      3beta,20alpha-diol was also detected as a final metabolic product via 20alpha
      dihydroprogesterone and 5alpha-pregnan-20alpha-ol-3-one. 5alpha-reduction (5alpha
      reductase type 1) and 20alpha-reduction were involved in the first step of
      metabolism. To identify the enzyme responsible for the 20alpha-reduction, we
      screened an U937 cDNA library, and obtained a clone (1.2 kb), which was identical
      to the human hepatic bile acid-binding protein or 20alpha-hydroxysteroid
      dehydrogenase (20alpha-HSD). 293 cells transfected with this cDNA demonstrated
      marked 20alpha-reduction of progesterone to 20alphaDHP, but 20alpha-oxidative,
      3alpha-HSD or 17beta-HSD activity was found to be negligible. In experimental
      animals, the importance of 20alpha-HSD has been reported to be involved in the
      protection of immune cells from the toxic effects of progesterone. Therefore, our
      present data suggest that 20alpha-HSD plays an important role in the regulation
      of progesterone actions in human immune cells.

PMID- 12507273
TI  - Exercise training increases the activity of pyruvate dehydrogenase complex in
      skeletal muscle of diabetic rats.
AB  - The effects of diabetes and exercise training on the activity of pyruvate
      dehydrogenase (PDH) complex in skeletal muscle were examined in rats. Male
      Sprague-Dawley rats were divided into four groups as follows: non-diabetic
      sedentary, non-diabetic trained, diabetic sedentary, and diabetic trained groups.
      Diabetic rats were prepared by a bolus injection of intravenous streptozotocin
      (50 mg/kg body weight). Exercise training was performed by having rats run on a
      treadmill at a speed of 25 m/min for 45 min/day, 6 days/wk for 4 wks. Exercise
      training decreased serum concentrations of glucose and non-esterified fatty acid
      in diabetic rats. GLUT4 content in skeletal muscle in sedentary rats was
      significantly decreased by diabetes; however, exercise training significantly
      increased the GLUT4 content in diabetic rats. The total and actual activities and
      the proportion of actual activity of the PDH complex were decreased in diabetic
      sedentary rats. Exercise training did not affect the total activity of the PDH
      complex in non-diabetic rats, whereas it increased the total activity in diabetic
      rats to the same level as that in non-diabetic rats. In diabetic rats, exercise
      training tended to increase the proportion of actual activity of the PDH complex
      from 2.7 +/- 0.4% to 4.7 +/- 0.8%, although the proportion of actual activity in
      non-diabetic rats was decreased by exercise training. The present study suggests
      that exercise training may improve glucose metabolism in the skeletal muscle of
      streptozotocin-induced diabetic rats probably through the mechanisms of
      increasing both GLUT4 content and the activity of the PDH complex.

PMID- 12507274
TI  - A successful pregnancy and delivery case of Graves' disease with myeloperoxidase
      antineutrophil cytoplasmic antibody induced by propylthiouracil.
AB  - A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was
      treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever
      from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO
      ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA
      level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative.
      There were no symptoms that indicated other diseases associated with MPO-ANCA.
      She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were
      elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole
      (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated
      the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also
      suspended because of the development of hepatic dysfunction. After thyroid
      function was normalized by administration of potassium iodide, she underwent
      subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation,
      which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to
      be one reason of low birth weight infant including hyperthyroidism. It is
      necessary to consider the appearance of the possibility of MPO-ANCA positive
      vasculitis in patients who are treated with PTU.

PMID- 12507275
TI  - Beta cell neogenesis from ducts and phenotypic conversion of residual islet cells
      in the adult pancreas of glucose intolerant mice induced by selective alloxan
      perfusion.
AB  - The aim of this study was to clarify the pattern of beta cell neogenesis in the
      alloxan-perfused, beta cells-depleted segment of glucose intolerant mice induced
      by selective alloxan perfusion. First, duct cells proliferated in the perfused
      segment, then cells co-expressing multiple islet hormones and transcription
      factors such as PDX-1, Nkx2.2, Isl1, and Pax6 were observed in duct cells, and
      newly formed islet-like cell clusters (ICCs) containing beta cells were
      recognized. In residual beta cell-depleted islets, glucagon or somatostatin and
      PDX-1 double-positive immature endocrine cells were recognized. Glucagon or
      somatostatin, insulin and PDX-1 triple-positive cells then appeared and these
      cells appeared to undergo terminal differentiation into beta cells. In
      conclusion, we demonstrated at least two different processes of beta cell
      neogenesis, i.e., formation of new ICCs from ductal epithelium and
      redifferentiation of residual non-beta islet cells in this model. In addition,
      transcription factors that appear in the processes of endocrine cell development
      may also play essential roles during beta cell neogenesis from duct cells.

PMID- 12507276
TI  - Decrease of serotonin and metabolite in the forebrain and facilitation of
      lordosis by dorsal raphe nucleus lesions in male rats.
AB  - In castrated male rats, a radiofrequency lesion was made in the dorsal raphe
      nucleus (DRL) and lordosis behavior was observed following treatment with
      estrogen. After the behavioral test, brains were removed and the contents of 5-HT
      and 5-HIAA in the forebrain were measured by high pressure liquid chromatography
      (HPLC). In the results, only 2 of 16 control males without brain surgery showed
      lordosis, and the mean lordosis quotient (LQ) was extremely low when compared to
      that in control females. In contrast, all male rats with DRL displayed lordosis
      and the mean LQ was higher than that of control males without brain surgery but
      lower than that in control females (P < 0.001). In the DRL males, 5-HT and 5-HIAA
      contents in the septum (SPT), the preoptic area (POA), the ventromedial
      hypothalamus (VMH) and the striatum (STM) were lower than those in control male
      and female groups (P < 0.001). These results suggest that the dorsal raphe
      nucleus prevents male rats from showing lordosis by serotonergic influence in the
      forebrain. In addition, HPLC results showed that levels of the 5-HT in the SPT,
      the POA and the VMH in the female group were higher than those in the control
      male group (P < 0.05). In female rats, the POA (P < 0.01) and the VMH (P < 0.05)
      contained larger 5-HT than those in the SPT and the STM, but there were no
      difference of 5-HT contents in the male rat.

PMID- 12507277
TI  - Phosphodiesterase 3 (PDE3) attenuates insulin secretion from the human pancreas:
      a specific PDE3 inhibitor improves insulin secretion in type II diabetes
      mellitus.

PMID- 12507278
TI  - Case report: esophageal collision tumor (oat cell carcinoma and adenocarcinoma)
      in Barrett's esophagus: immunohistochemical, electron microscopy and LOH
      analysis.
AB  - We report a case of an esophageal collision tumor composed of adenocarcinoma and
      oat cell carcinoma. Both tumors appeared to arise from dysplastic Barrett's
      mucosae in a 75-year-old man. Immunohistochemical stains and electron microscopy
      demonstrated a separate identity for each of the tumors in collision. Molecular
      analysis of microsatellite regions was performed in different microdissected
      areas. Identical loss of heterozygosity (LOH) at 9p21 and 17p13 was determined in
      the three different microdissected areas of the adenocarcinoma component. LOH was
      not determined in any area of the oat cell carcinoma. This is the first study
      that analyzes the allele status of an esophageal collision tumor. Our findings
      suggest a biclonal origin for both components of the collision tumor.

PMID- 12507279
TI  - Postnatal development of female sheep pineal gland under natural inhibitory
      photoperiods: an immunocytochemical and physiological (melatonin concentration)
      study.
AB  - The purpose of this study was to determine structural and immunocytochemical
      changes taking place during the day and at night in developing sheep pineal gland
      under natural non-stimulatory photoperiods (summer solstice). Additionally, the
      diurnal cycle of plasma melatonin levels was charted and differences between
      diurnal and nocturnal pineal melatonin concentrations were analyzed. 36 ewes of
      three different ages were examined: infants (1-6 months old), pubertal and early
      fertile age (9-24 months old) and adults (36-60 months old). Plasma and pineal
      gland melatonin levels were higher in pubertal sheep than in infants or adults.
      Pubertal sheep pineal glands were also heavier, contained a larger number of
      pinealocytes and interstitial cells and displayed more evident innervation and
      vascularisation than infants or adults. There was no difference in the number of
      pinealocytes and interstitial cells between animals killed during daylight or at
      night. Gland weight, pinealocyte nuclear profile areas and plasma melatonin
      concentrations were all significantly higher at night than during the day.

PMID- 12507280
TI  - Morphological hysteresis of the small airways.
AB  - The resistance to airflow that develops in most obstructive processes takes place
      in the small airways. The aim of the present paper is to describe bronchial
      hysteresis morphometrically in a respiratory cycle model. As a working
      hypothesis, it is proposed that the changes that take place in the respiratory
      tract during the respiratory cycle are related to the bronchial size. Specimen
      rat lungs were organized into five groups: In the first group, the lungs were
      filled with a liquid fixative to 25 cm of H2O transpulmonary pressure. The
      following four groups were inflated with air and fixed through the pulmonary
      artery. Groups 2 and 3 were fixed at 10 and 20 cm transpulmonary pressure in
      inflation. The last two groups were fixed in deflation and, for this purpose, the
      transpulmonary pressure was increased to 27 cm and decreased to 20 and 10 cm,
      respectively. The lungs were processed for morphometrical study and the following
      variables were quantified: pulmonary volume, internal area, internal perimeter,
      wall area, internal area radius and bronchial wall radius. The diameter of the
      airways studied varied between 84.06 microm and 526.4 microm. The results were
      classified into three subgroups consisting of small, medium-sized and large
      bronchi. With a single exception--the internal area in the medium-sized bronchi
      inflated to 20 cm--all the results obtained in deflation were higher than those
      obtained in inflation. The internal area increased or decreased significantly
      upon raising or lowering the transpulmonary pressure respectively, in the small
      and medium-sized bronchi. The wall area in the large bronchi showed significant
      differences between inflation and deflation at 10 and 20 cm transpulmonary
      pressure. The wall area was modified significantly in the lungs fixed at 20 cm in
      the small bronchi and at 10 cm in medium-sized bronchi. The bronchial wall radius
      was significantly greater in the large bronchi and smaller in the small bronchi.
      The lumen of the medium-sized and small bronchi increases in inspiration and
      decreases in expiration. The wall thickness displayed differences between
      inflation and deflation. The most marked hysteresis was presented by the
      bronchial wall in the large bronchi. Our results suggest that the behavior of the
      bronchi varies according to their size.

PMID- 12507281
TI  - Dynamic assembly of tight junction-associated proteins ZO-1, ZO-2, ZO-3 and
      occludin during mouse tooth development.
AB  - Tight junctions might play a role during tissue morphogenesis and cell
      differentiation. In order to address these questions, we have studied the
      distribution pattern of the tight junction-associated proteins ZO-1, ZO-2, ZO-3
      and occludin in the developing mouse tooth as a model. A specific temporal and
      spatial distribution of tight junction-associated proteins during tooth
      development was observed. ZO-1 appeared discontinuously in the cell membrane of
      enamel organ and dental mesenchyme cells. However, endothelial cells of the
      dental mesenchyme capillaries displayed a continuous fluorescence at the cell
      membrane. Inner dental epithelium first showed an evident signal for ZO-1 at the
      basal pole of the cells at bud/cap stage, but ZO-1 was accumulated at the basal
      and apical pole of preameloblast/ameloblasts at late bell stage. Surprisingly, in
      the incisor ZO-1 decreased as the inner dental epithelium differentiated, and was
      re-expressed in secretory and mature ameloblasts. On the contrary, ZO-2 was
      confined to continuous cell-cell contacts of the enamel organ in both molars and
      incisors. The lateral cell membrane of inner dental epithelial cells was
      specifically ZO-2 labeled. However, ZO-3 was expressed in oral epithelium whereas
      dental embryo tissues were negative. In addition, occludin was hardly detected in
      dental tissues at the early stage of tooth development, but was distributed
      continuously at the cell membrane of endothelial cells of ED19.5 dental
      mesenchyme. In incisors, occludin was detected at the cell membrane of the
      secretory pole of ameloblasts. The occurrence and relation during tooth
      development of tight junction proteins ZO-1, ZO-2 and occludin, but not ZO-3,
      suggests a combinatory assembly in tooth morphogenesis and cell differentiation.

PMID- 12507282
TI  - A COX-2 inhibitor, nimesulide, inhibits chemically-induced rat tongue
      carcinogenesis through suppression of cell proliferation activity and COX-2 and
      iNOS expression.
AB  - The modifying effects of a cyclooxygenase (cox)-2 selective inhibitor nimesulide
      on tongue carcinogenesis were investigated in male F344 rats initiated with 4
      nitroquinoline-1-oxide (4-NQO). The cell proliferation activity measured by
      proliferating cell nuclear antigen (PCNA)-positive index and apoptotic index, and
      the immunohistochemical expression of COX-2, and inducible nitric oxide synthase
      (iNOS) in the tongue mucosa or neoplasms were also examined for mechanistic
      analysis of modifying effects of nimesulide on tongue carcinogenesis. All animals
      except those treated with nimesulide alone and untreated rats were given 20 ppm 4
      NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week
      after the cessation of 4-NQO exposure, rats given 4-NQO were fed the experimental
      diets containing nimesulide (100 and 400 ppm) for 22 weeks. At week 32, the
      incidence of tongue squamous cell carcinoma was significantly reduced by feeding
      of the diet containing 400 ppm nimesulide. Feeding of nimesulide significantly
      decreased polyamine content and PCNA-labeling index in tongue carcinoma.
      Apoptotic index in tongue carcinoma was increased by feeding of nimesulide. In
      addition, nimesulide feeding reduced COX-2 and iNOS expression in the tongue
      dysplasia and neoplasms. These results suggest that 400 ppm nimesulide in diet,
      when given during the promotion phase, exerts chemopreventive ability against 4
      NQO-induced tongue tumorigenesis through inhibition of cell proliferation
      activity in conjunction with modification of COX-2 and iNOS expression of the
      target lesions.

PMID- 12507283
TI  - Styrene hepatotoxicity in rats treated by inhalation or intraperitoneally: a
      structural investigation.
AB  - The purpose of this study was to investigate the toxicity of styrene in the liver
      of adult rats treated either by inhalation of styrene vapour (300 ppm, 6 h/d, 5
      d/wk, for 2 wk) or intraperitoneally with different styrene doses (4, 40, 400
      mg/Kg) for 3 consecutive days. Using a light microscope, some alterations of
      liver parenchyma and sinusoid dilation were noticed, more marked in the group
      treated with the intraperitoneal administration of the chemical. Using an
      electron microscope, some additional changes were observed (once again, more
      marked in the latter group of rats): a) an increase in the content of lipids
      inside hepatocytes, and b) the rise of intracytoplasmic, intercellular and
      perisinusoidal collagen fibres. Therefore, cell damage and functional disturbance
      of sinusoids due to perisinusoidal fibrosis are apparent in the liver of both
      groups of rats exposed to styrene treatment, but these changes are definitely
      more significant in those subjected to intraperitoneal administration.

PMID- 12507284
TI  - In vitro effects of hormones and autacoids on the hydrogen peroxide production
      and the morphology of endotoxin-activated rat peritoneal macrophages.
AB  - Peritoneal macrophages activated in vitro by endotoxin exhibit alterations of
      their capability to produce hydrogen peroxide after phorbol ester stimulation
      when certain hormones or autacoids are present in the culture medium. They also
      show morphological changes, mainly concerning cell size and nuclear appearance.
      Agents known to increase the intracellular levels of cyclic AMP, e.g. adrenalin
      and PGE2 reduce the hydrogen peroxide production. Insulin, which is known to
      decrease cyclic AMP levels, produces opposite results. Agents postulated to act
      via phospholipase C, e.g. serotonin, augment the production of hydrogen peroxide.
      We assume that this form of modulation may represent a regulatory mechanism of
      macrophage activation.

PMID- 12507285
TI  - Mitosin, a novel marker of cell proliferation and early recurrence in
      intracranial meningiomas.
AB  - The expression of mitosin, a novel proliferation-associated molecule was
      evaluated immunohistochemically in a consecutive series of 47 patients with
      primary intracranial benign and atypical meningiomas. Mitosin expression was
      correlated with proliferation markers Ki-67 (MIB-1), proliferating cell nuclear
      antigen (PCNA), topoisomerase IIalpha (TopoIIalpha) and mitotic index, as well as
      with standard clinicopathological parameters and patient outcome. Seven tumors
      recurred (14.8%) following gross total resection, within a follow-up period
      ranging from 21 to 108 months (median 60 months). The higher proliferation
      indices were obtained with mitosin and PCNA and the lower ones with TopoIIalpha.
      Mitosin labeling index (LI) ranged from 0.1 to 57% (median 3%), with a
      significant overlapping of values between grades. A significant positive
      correlation was shown between mitosin LI on the one hand and Ki-67 LI (p <
      0.001), or the mitotic index (p = 0.027) on the other. The incidence of
      recurrence was higher in cases with a mitosin LI higher than 3% (p = 0.048).
      Univariate analysis disclosed mitosin LI (p = 0.033) along with the mitotic index
      (p = 0.024) and tumor size (p = 0.028) as significant predictors of shortened
      recurrence-free survival. In multivariate analysis, the labeling indices of
      mitosin (p = 0.035) and Ki-67 (p = 0.032), along with tumor size, were shown to
      provide independent prognostic information, beyond that obtained by standard
      clinical and pathological parameters. However, as indicated by factor analysis,
      the prognostic information yielded by mitosin was superior to that provided by
      the remaining proliferation markers (p = 0.041). We conclude that mitosin
      immunohistochemical expression, although failing to discriminate between benign
      and atypical meningiomas, may be of use as a novel cell proliferation marker and
      as a predictor of tumor recurrence.

PMID- 12507286
TI  - The immunohistochemical expression of metallothionein in inflammatory bowel
      disease. Correlation with HLA-DR antigen expression, lymphocyte subpopulations
      and proliferation-associated indices.
AB  - Metallothionein (MT) expression in intestinal resection specimens from 41
      patients with ulcerative colitis (UC) and 10 patients with Crohn's disease (CD )
      was immunohistochemically studied by the avidin-biotin (ABC) method. In addition,
      the possible relationship of its expression with HLA-DR antigen expression,
      lymphocyte subpopulations and proliferation-associated indices was studied in
      order to elucidate the role of this molecule in inflammatory bowel disease (IBD).
      The MT immunoreactivity was recorded by staining and intensity-distribution
      scores. MT staining varied in and was mainly localized in the cytoplasm, although
      a combined nuclear/cytoplasmic reactive pattern was also seen in epithelial
      cells. MT expression was decreased in UC, and CD compared with normal mucosa. No
      difference in MT expression between UC and CD was noted. In UC, a gradually
      decreased expression from remission, to resolving and to active phase was
      observed. An inverse correlation of MT expression with HLA-DR antigen expression
      was detected (p = 0.018) in the cases of UC. The data suggest that a low level of
      MT expression in inflammatory bowel disease and particularly in active phase of
      UC may indicate a decreased endogenous intestinal protection and it may be
      implicated in the pathogenesis of the disease.

PMID- 12507287
TI  - Expression of c-fos and c-jun protooncogenes in the uteri of immature mice
      neonatally exposed to diethylstilbestrol.
AB  - We studied the cell-type-specific and temporal expression of c-fos and c-jun
      protooncogenes after 17beta-estradiol (E2) stimulation in the uteri of immature 3
      week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the
      ontogenic expression of these genes in the uteri of DES-mice using
      immunohistochemistry and in situ hybridization. A single E2 injection induced the
      transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial
      epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle
      treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2
      injection and that of protein expression was 2 to 3 hours after the injection.
      The expression of c-fos mRNA and protein after E2 stimulation was lower in the
      DES-mice than in the control animals. There were no significant differences in
      the c-jun expression patterns in both experimental groups before and after the E2
      injection. The E2 injection transiently down-regulated the c-jun expression in
      the epithelium and up-regulated it in the stroma and myometrium. The uterine
      epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and
      10, compared with those of controls. Neonatal DES treatment reduced c-Jun
      immunoreactivity in the uterine epithelium on days 4 and 10, and increased the
      reaction in the stroma on day 4. These results suggested that the neonatal DES
      treatment induces permanent changes in the c-fos expression pattern independent
      of the postpuberal secretion of ovarian steroids. The changes in the expression
      of c-fos and c-jun protooncogenes, particularly during postnatal development, are
      likely to play important roles in the production of uterine abnormalities in the
      DES-mice.

PMID- 12507288
TI  - Diagnostic differentiation of essential thrombocythaemia from thrombocythaemias
      associated with chronic idiopathic myelofibrosis by discriminate analysis of bone
      marrow features--a clinicopathological study on 272 patients.
AB  - Until now diagnosis of essential thrombocythaemia (ET) is generally performed by
      following the criteria of the Polycythaemia Vera Study Group (PVSG) that only
      marginally regards morphological features. Bone marrow biopsies were studied from
      272 patients with ET in strict accordance with the PVSG guidelines and also from
      35 control patients with reactive thrombocytosis. To define morphological
      features of distinctive impact more accurately, we performed a stepwise
      discriminant analysis of 16 morphological parameters based on histochemical
      staining reactions and semiquantitative grading of standardized features. A clear
      cut separation into three distinctive histological patterns was accomplished that
      showed in more than 96% a correct predicted classification. Variables of
      significant impact included fibre content, quantity and cytological abnormalities
      of megakaryopoiesis like bulbous (cloud-like) nuclei, degree of nuclear
      lobulation and presence of giant forms. These changes were not detectable in the
      control group. The different constellations of histopathological features could
      be assigned to true ET (98 patients) and false ET, i.e. 136 patients with
      prefibrotic and 38 patients with early fibrotic chronic idiopathic myelofibrosis
      (IMF) accompanied by thrombocythaemia. A re-evaluation of clinical findings was
      in keeping with this classification into three categories that exerted
      significant differences to develop myelofibrosis during observation time and also
      different survival patterns. Contrasting IMF true ET is characterized by a
      pronounced proliferation of the megakaryocyte lineage showing large to giant
      cells without maturation defects and no relevant increase in reticulin fibres.
      Discrimination between these entities is warranted, because of a significant
      difference in presenting haematological data, follow-up and life expectancy.

PMID- 12507289
TI  - A comparison between double and triple therapies of octreotide, galanin and
      serotonin on a rat colon carcinoma.
AB  - Sixty female nude mice (C578L/6jBom-nu) were injected with 100 microl cell
      suspension containing 2 x 10(6) viable cells of an N-methyl-N-nitroguanidine
      induced rat colonic adenocarcinoma. After seven days the animals were divided
      into five groups. The first group received only saline and served as a control
      group. The second group received a triple therapy of octreotide, galanin and
      serotonin (20 microg/kg). The last three groups received double therapies of
      octreotide/galanin, octreotide/serotonin or galanin/serotonin (20 microg/kg).
      They were treated twice a day for five days. Tumour volume and weight, relative
      volume density of tumour-feeding blood vessels and of tumour necrotic tissue, as
      well as apoptotic and proliferation indices were determined. Animal weight, food
      consumption, faeces weight and its water content were recorded before and after
      treatment. Tumour volume was significantly reduced only in the group that
      received the triple therapy. The volume density of the tumour-feeding blood
      vessels was significantly reduced in the treated groups with the exception of the
      group that received octreotide and serotonin. Increased relative volume density
      of tumour necrotic tissue occurred only in the group treated with triple therapy.
      Apoptotic indices were significantly increased in all treated groups. No
      statistical difference was found between treated animals and controls regarding
      proliferation indices, food consumption, faeces weight and water content or
      animal weight. In conclusion, double therapy using two of the gastrointestinal
      bioactive substances, octreotide, galanin and serotonin, has certain effects on
      colon cancer cells. To cause a considerable tumour necrosis, triple therapy seems
      to be required. Both double and triple therapy seem to lack obvious side-effects.

PMID- 12507290
TI  - Scanning electron microscopic examinations on retarded bone defect healing in
      spontaneously diabetic BB/O(ttawa)K(arlsburg) rats.
AB  - To date, no detailed knowledge from animal experiments is available on the kind
      and extent of osseous and mineral metabolic disorders in genetically determined,
      insulin-dependent Type I diabetes. The purpose of this study was to examine the
      influence of the diabetic metabolic state in spontaneously diabetic
      BB/O(ttawa)K(arlsburg) rats on bone defect healing. Eighty spontaneously-diabetic
      BB/OK rats with a blood-glucose value of 391 +/- 106 mg% (mean +/- SD) at the
      time of manifestation were used in the study. Based on blood-glucose values at
      the time of surgery (mg%), postoperative blood-glucose course (mg%) and
      postoperative insulin requirements (IU/kg), the animals were divided into groups
      with well-compensated (n = 40, 170 +/- 101 mg%; 221 +/- 120 mg%; 2.1 +/- 1 IU/kg)
      or poorly compensated (n = 40; 371 +/- 158 mg%; 357 +/- 83 mg%; 5.2 +/- 1.4
      IU/kg) metabolic state. Forty LEW.1A rats served as the normoglycemic controls
      (95 +/- 18 mg%). Using a 1-mm-diameter Kirschner wire, a hole of femoral bone ca.
      1 cm proximal to the knee joint space was centrally drilled. Ten animals from
      each group were killed on postoperative days 7, 14, 24, and 42, and specimens
      were taken for analysis. Using SEM to measure regions of new bone
      semiautomatically and quantitatively, also determining the number, area, and
      circumference of regions not yet filled with new bone. Up to postoperative day
      14, very significant differences (p < 0.0001) for all investigated
      characteristics were found between the spontaneously-diabetic BB/OK rats and the
      control animals--in favor of the controls--and up to postoperative day 24 within
      the group of spontaneously-diabetic BB/OK rats, where the well-compensated
      animals had significantly better results in terms of number and area of regions
      of bone not yet filled with new bone formations. Forty-two days postoperatively,
      SEM observations showed no differences between examination groups. The process of
      bone defect healing in spontaneously-diabetic rats was disturbed only in the
      early phase and exhibited retardation in its progression. After 42 days, bone
      defect healing was complete, regardless of the diabetic metabolic state; no
      differences were detected with the SEM between examination groups at this time
      point.

PMID- 12507291
TI  - Distinct expression of calnexin in major human salivary glands.
AB  - Calnexin (Cnx) has been characterized as a membrane-bound protein that
      transiently interacts in a unique chaperone system with newly synthesized
      glycoproteins in order to allow the establishment of their proper tertiary and,
      in most cases, quarternary structures. The aim of the study was to identify and
      to locate the expression of Cnx in the three major salivary glands of humans by
      different methods. Strong expression of Cnx protein and mRNA were generally found
      in serous salivary secretory units. With regard to mucous secretory units,
      expression of Cnx was only detectable at a low level in mucous acinar cells of
      sublingual glands, but not of submandibular glands. Expression of Cnx was always
      preserved in the surface epithelium of intralobar and interlobular duct segments.
      In addition, expression of Cnx was detected in sebaceous glands of parotid
      tissues, with a distribution pattern resembling that seen in sebaceous glands of
      the normal skin. In conclusion, production of saliva is associated with the
      expression of Cnx. Synthesis of molecules in mucous secretory units is not
      necessarily associated with a strong Cnx expression, whereas synthesis in serous
      secretory units apparently is. The tissue-specific Cnx expression is also
      paralleled by the observation that the secretions produced by the major salivary
      glands differ in their composition and amount.

PMID- 12507292
TI  - Immunohistochemical localization of truncated midkine in developing human bile
      ducts.
AB  - Midkine (MK) is a heparin-binding growth factor whose gene has been identified in
      embryonal carcinoma cells in early stages of retinoic acid-induced
      differentiation. In the present study, we investigated the developmental
      localization of truncated MK protein in human bile ducts. Thirty specimens of the
      livers from 25 fetuses (from 9 to 40 gestational weeks) and from five neonates
      less than 4 weeks old were examined. Immunohistochemical analysis was performed
      using a mouse IgG2b monoclonal antibody against recombinant-truncated MK.
      Truncated MK was expressed moderately in the fetal liver from 9 to 15 gestational
      weeks. The immunoreactivities were found in the primitive hepatocytes, ductal
      plates, migrating biliary cells and immature bile ducts. The reaction products
      were localized in the cytoplasm heterogeneously. The intensity of immunostaining
      was weak from 15 gestational weeks to 26 gestational weeks. After 27 gestational
      weeks, truncated MK was not detected in the fetal livers. It was suggested that
      primitive hepatocytes, ductal plates and immature bile ducts produced truncated
      MK transiently during human bile ducts development.

PMID- 12507293
TI  - Immunohistochemical localization of human fructose-1,6-bisphosphatase in
      subcellular structures of myocytes.
AB  - The localization of fructose-1,6-bisphosphatase (FBPase) in human skeletal muscle
      was determined immunohistochemically using polyclonal antibodies. Light
      microscopy analysis, confirmed with the use of confocal microscopy, indicated
      that the enzyme is localized on both sides of the Z line of myocytes. The
      immunohistochemical investigation was confirmed by a co-sedimentation experiment
      which revealed that muscle FBPase binds strongly to alpha-actinin--a major
      structural protein of the Z line. This is the first report on localization of
      FBPase in skeletal muscle tissue.

PMID- 12507294
TI  - Expression of retinoblastoma gene product in respiratory epithelium and sinonasal
      neoplasms: relationship with p16 and cyclin D1 expression.
AB  - Transition from G1 to S phase of the cell cycle is mediated by interactions
      between the Retinoblastoma gene product (pRb), p16, and cyclin D1. To determine
      the expression of these proteins in the sinonasal mucosa immunohistochemistry was
      carried out on archived tissue sections from 46 patients (37 men, 9 women, age
      range 17 to 82 years, median 55 years). Nuclear immunostaining for these proteins
      was assessed and the expression rates (percentages of immunoreactive nuclei) in
      normal respiratory epithelium, inverted sinonasal papillomas, cylindrical
      (oncocytic) sinonasal papillomas, and squamous cell carcinomas were compared.
      Normal respiratory epithelium showed significantly higher pRb expression in
      surface cells compared to basal cells (p < 0.05). In contrast, abundant pRb
      expression in surface and basal cells was detected in columnar differentiation in
      sinonasal papillomas and adjacent mucosa. Cuboidal and squamous metaplasia in
      inverted papillomas showed significantly reduced pRb expression in surface cells
      compared to columnar epithelium in inverted papillomas (p < 0.05, respectively).
      Expression of p16 was detected in all epithelial cell layers of normal
      respiratory epithelium, sinonasal papillomas, and adjacent mucosa. Cuboidal and
      squamous metaplasia in inverted papillomas showed increased p16 expression in
      surface cells compared to columnar epithelium in inverted papillomas (p < 0.05
      between squamous metaplasia and columnar epithelium). Sinonasal squamous cell
      carcinomas showed the coexpression of pRb and p16. Expression rates of cyclin D1
      higher than 10% were detected only in invasive carcinomas but not in carcinoma in
      situ, sinonasal papillomas or respiratory epithelium. Conclusively, pRb
      expression accompanies terminal differentiation in columnar surface cells.
      Expression of pRb in proliferating basal cells is present in sinonasal papillomas
      and adjacent mucosa but not in normal respiratory epithelium. Cuboidal and
      squamous metaplasia in inverted papillomas involves downregulation of pRb
      expression along with increased p16 expression in surface cells. Sinonasal
      squamous cell carcinomas coexpress pRb and p16. Overexpression of cyclin D1 in
      sinonasal lesions is confined to invasive squamous cell carcinomas.

PMID- 12507295
TI  - Angiogenesis after sintered bone implantation in rat parietal bone.
AB  - We studied the effect of bone substitutes on revascularization and the restart of
      blood supply after sintered bone implantation in comparison with synthetic
      hydroxyapatite implantation and fresh autogenous bone transplantation (control)
      in rat parietal bones. Methods for the study included the microvascular corrosion
      cast method and immunohistochemical techniques were also used. The
      revascularization of the control group was the same as that for usual wound
      healing in the observations of the microvascular corrosion casts. The sintered
      bone implantation group was quite similar to that of the control group. In the
      synthetic hydroxyapatite group, immature newly-formed blood vessels existed even
      on the 21st day after implantation and the physiological process of angiogenesis
      was interrupted. Immunohistochemically, vascular endothelial growth factor
      (VEGF), which activates angiogenesis, appeared at the early stages of both the
      control group and the sintered bone implantation group. VEGF reduced parallel
      with the appearance of the transforming growth factor factor-beta-1 (TGF-beta-1),
      which obstructs angiogenesis, and the angiogenesis passed gradually into the
      mature stage. In the hydroxyapatite implantation group, TGF-beta-1 appeared at
      the early stage of the implants. The appearance of VEGF lagged and it existed
      around the pores of hydroxyapatite even on the 21st day of the implantation.
      Proliferation and wandering of endothelial cells continued without any maturing
      of the vessels. These findings suggest that the structure and the components of
      the implant material affect angiogenesis after implantation as well as new bone
      formation.

PMID- 12507296
TI  - Review of chromophobe renal cell carcinoma with focus on clinical and
      pathobiological aspects.
AB  - In recent years, the concept of chromophobe renal cell carcinoma (RCC) has been
      established. Chromophobe RCCs account for about 4-6% of all renal tumors.
      Macroscopically, the cut surface of the tumor is generally grey-beige in color.
      Histologically, there are two variants (typical and eosinophilic). In the typical
      variant, large tumor cells with architecture of a compact tubulo-cystic pattern
      proliferate. The cytoplasm is abundant and shows a fine reticular translucent
      pattern. The cell border is thick, prominent and eosinophilic. In the
      eosinophilic variant, tumor cells are smaller and markedly eosinophilic, and a
      perinuclear halo is often seen. Histochemically, the tumor cells generally show a
      diffuse and strong reaction for Hale's colloidal iron staining.
      Ultrastructurally, tumor cells contain many cytoplasmic microvesicles (150-300
      nm). In chromosomal analysis, a low chromosome number is characteristic of
      chromophobe RCCs, due to the frequent occurrence of a combined loss of
      chromosomes 1, 2, 6, 10, 13, 17, and 21. In differential diagnosis, histological
      distinction from oncocytomas, which share a common phenotype (intercalated cells
      of the collecting duct system), is most important. In this diagnostic setting,
      recent studies have given rise to several problems. Firstly, some cases of
      coexistent chromophobe RCC and oncocytoma (so-called renal oncocytosis) or cases
      of oncocytoma with metastasis have recently been reported. Secondly, the
      existence of chromophobe adenoma, which is the benign counterpart of chromophobe
      RCC, and an oncocytic variant of chromophobe RCC has recently been suggested.
      Therefore, further studies are needed to elucidate the relationship between
      chromophobe RCCs and oncocytomas, to confirm whether chromophobe adenoma actually
      exists or not, and to identify the key gene that causes chromophobe RCCs.

PMID- 12507297
TI  - Metabotropic glutamate receptors promote neuronal and vascular plasticity through
      novel intracellular pathways.
AB  - During the initial development and maturation of an individual, the metabotropic
      glutamate receptor (mGluR) system becomes a necessary component for the critical
      integration of cellular function and plasticity. In addition to the maintenance
      of cellular physiology, the mGluR system plays a critical role during acute and
      chronic degenerative disorders of the central nervous system. By coupling to
      guanosine-nucleotide-binding proteins (G-proteins), the mGluR system employs a
      broad range of signal transduction systems to regulate cell survival and injury.
      More commonly, it is the activation of specific mGluR subtypes that can prevent
      programmed cell death (PCD) consisting of two distinct pathways of genomic DNA
      degradation and membrane phosphatidylserine (PS) residue exposure. To offer this
      cellular protection, mGluRs modulate a series of down-stream cellular pathways
      that include protein kinases, mitochondrial membrane potential, cysteine
      proteases, intracellular pH, endonucleases, and mitogen activated protein
      kinases. Prevention of cellular injury by the mGluR system is directly applicable
      to clinical disability, since immediate and delayed injury paradigms demonstrate
      the ability of this system to reverse PCD in both neuronal and vascular cell
      populations. Further understanding of the intricate pathways that determine the
      protective nature of the mGluR system will provide new therapeutic avenues for
      the treatment of neurodegenerative disorders.

PMID- 12507298
TI  - Murine embryonic stem cell in vitro differentiation: applications to the study of
      vascular development.
AB  - The present review summarizes knowledge accumulated during the last decade
      concerning in vitro endothelial differentiation from embryonic stem (ES) cells.
      There is now growing evidence that ES cells may provide a powerful model system
      to determine the cellular and molecular mechanisms of vascular development. ES
      cells differentiate into the endothelial lineage by successive maturation steps
      recapitulating in vivo events observed in the embryo. Further maturation of ES
      derived embryoid bodies either in three dimensional gels or in confrontation
      cultures with tumor spheroids can also provide a model of physiological or
      tumoral angiogenesis. The data obtained from experimental in vitro
      differentiation of genetically modified mouse ES cells highlight the potential
      and the complementarity of this model system to in vivo gene knock out studies.
      We also consider and discuss some of the potential applications of ES cell
      technology in vascular biology for future directions in basic research and
      medicine, by manipulation of differentiation and the generation of cell
      populations for analysis and transplantation for therapeutic use.

PMID- 12507299
TI  - Modeling human breast cancer metastasis in mice: maspin as a paradigm.
AB  - Breast cancer is the most common cancer detected in women, accounting for nearly
      one out of every three cancers diagnosed in the United States. Most cancer
      patients do not die from the primary tumor but die due to metastasis. Therefore,
      the study of metastasis is of most importance both to the clinician and patient.
      In the past, animal models have been used in breast cancer research and mammary
      gland biology. Our group has also established several animal models to address
      the function of a novel tumor suppressor gene maspin in breast tumor progression.
      Maspin was initially isolated from normal mammary epithelial cells. Its
      expression was down regulated in breast tumors. To test the protective role of
      maspin overexpression in mammary tumor progression, we crossed maspin
      overexpression transgenic mice (WAP-maspin) with a strain of oncogenic WAP-SV40 T
      antigen mice. The bitransgenic mice had reduced tumor growth rate and metastasis.
      Maspin overexpression increased the rate of apoptosis of both preneoplastic and
      carcinomatous mammary epithelial cells. Maspin reduced tumor growth through a
      combination of reduced angiogenesis and increased apoptosis. In a separate animal
      experiment, maspin overexpressing mammary tumor cells (TM40D) were implanted into
      the fat pad of syngeneic mice. TM40D tumor cells were very invasive and
      metastatic. However, both primary tumor growth and metastasis were significantly
      blocked in TM40D cells that overexpress maspin as a consequence of plasmid or
      retrovirus infection. These evidences demonstrate that maspin function to inhibit
      primary tumor growth as well as invasion and metastasis. Elucidating the
      molecular mechanism of maspin action will shed light on our understanding of
      breast cancer invasion and metastasis.

PMID- 12507300
TI  - Molecular biology of glioma tumorigenesis.
AB  - Gliomas are the most common intracranial malignant tumors in humans, and high
      grade gliomas in particular pose a unique challenge due to their propensity for
      proliferation and tissue invasion. Our understanding of glioma oncogenesis,
      proliferation, and invasion has been greatly advanced in the past 10 years as
      researchers have gained a better understanding of the molecular biology of these
      tumors. This article highlights glioma histopathology, as well as cytogenetic and
      molecular alterations associated with the pathogenesis of human gliomas. It is
      hoped that better understanding of the molecular pathogenesis of gliomas will
      improve tumor classification as well as lead to novel targets for therapy and
      prognostic markers.

PMID- 12507301
TI  - Exploring the connection between chronic renal fibrosis and bone morphogenic
      protein-7.
AB  - Tubulointerstitial fibrosis is a hallmark feature of chronic renal injury.
      Specific therapies to control the progression of renal fibrosis towards end-stage
      renal failure are still limited. Transforming growth factor-beta1 (TGF-beta1) has
      been identified as a major mediator of renal fibrosis. Recent reports have
      suggested that Bone Morphogenic Protein-7 (BMP-7), another member of the TGF-beta
      superfamily, accelerates repair of acute renal injury and ameliorates progression
      of chronic renal fibrosis in a variety of animal models. Interestingly, BMP-7, an
      endogenous molecule which is present in the normal kidney, vastly decreases its
      expression during renal injury. Although, the mechanism of BMP-7 action in the
      kidney is not yet fully understood, the idea of an endogenous molecule with reno
      protective function is intriguing.

PMID- 12507302
TI  - Human syndromes with genomic instability and multiprotein machines that repair
      DNA double-strand breaks.
AB  - The present report deals with the functional relationships among protein
      complexes which, when mutated, are responsible for four human syndromes
      displaying cancer proneness, and whose cells are deficient in DNA double-strand
      break (DSB) repair. In some of them, the cells are also unable to activate the
      proper checkpoint, while in the others an unduly override of the checkpoint
      induced arrest occurs. As a consequence, all these patients display genome
      instability. In ataxia-telangiectasia, the mutated protein (ATM) is a kinase,
      which acts as a transducer of DNA damage signalling. The defective protein in the
      ataxia-telangiectasia-like disorder is a DNase (the Mre11 nuclease) that in vivo
      produces single-strand tails at both sides of DSBs. Mre11 is always present with
      the Rad50 ATPase in a protein machine: the nuclease complex. In mammals, this
      complex also contains nibrin, the protein mutated in the Nijmegen syndrome.
      Nibrin confers new abilities to the nuclease complex, and can also bind to BRCA1
      (one of the two proteins mutated in familial breast cancer). BRCA1 has a central
      motif that binds with high affinity to cruciform DNA, a structure present in
      places where the DNA loops are anchored to the chromosomal axis or scaffold. The
      BRCA1 x cruciform DNA complex should be released to allow the nuclease complex to
      work in DNA recombinational repair of DSBs. BRCA1 also acts as a scaffold for the
      assembly of ATPases such as Rad51, responsible for the somatic homologous
      recombination. Loss of the BRCA1 gene prevents cell survival after exposure to
      cross-linkers. The BRCA1-RING domain is an E3-ubiquitin ligase. It can mono
      ubiquitinate the FANCD2 protein, mutated in one of the Fanconi anemia
      complementation groups, to regulate it. Finally, during DNA replication, the
      nuclease complex and its activating ATM kinase are integrated in the BRCA1
      associated surveillance complex (BASC) that contains, among others, enzymes
      required for mismatch excision repair. In short, the proteins missing in these
      syndromes have in common their BRCA1-mediated assembly into multimeric machines
      responsible for the surveillance of DNA replication, DSB recombinational repair,
      and the removal of DNA cross-links.

PMID- 12507303
TI  - PTTG and cancer.
AB  - Pituitary tumor transforming gene (pttg) is a recently isolated oncogene that is
      expressed in most of the tumors. Overexpression of pttg results in an increase in
      cell proliferation, induces cell transformation in vitro, and promotes tumor
      formation in nude mice. The gene encodes a protein of 202 amino acids with no
      significant homology with other known proteins. The protein is a multi domain
      consisting of a transactivation domain, domain required for ubiquitin-mediated
      proteolysis and a DNA binding domain. pttg protein is bestowed with a multitude
      of functions and seems to be involved in most of the important mechanisms of cell
      proliferation, differentiation and signaling. Given the number of processes that
      are involved in the manifestation of cancer, it thus becomes mandatory to study
      the role of this potent oncogene in relation to the processes of cell survival,
      death and functioning.

PMID- 12507304
TI  - Review of metanephric adenoma of the kidney with focus on clinical and
      pathobiological aspects.
AB  - The concept of metanephric adenoma has become established in recent years.
      Metanephric adenoma is a rare neoplasm. Macroscopically, the cut surface of the
      tumor displays a tan to gray or yellow color, and tumors generally form well
      circumscribed masses. Histologically, tumors are composed of small epithelial
      cells that form small acini. Glomeruloid bodies, which are composed of lobulated
      papillary projections, are occasionally seen. Although there have been few
      studies using chromosomal analysis, two recent studies have shown partial
      monosomy or LOH of 2p. On the other hand, the concept of metanephric tumors has
      recently become broadened. These tumors include metanephric adenomas,
      adenofibromas and stromal tumors, and they compose a continuous histological
      spectrum. Therefore, further studies on various aspects are needed to identify
      the gene responsible for the occurrence of metanephric tumors and, furthermore,
      to clarify the association among the three types of metanephric tumors.

PMID- 12507305
TI  - Molecular pathogenesis of urothelial bladder cancer.
AB  - Carcinoma of the urinary bladder is the second most common urologic malignancy.
      In addition, these tumors are one of the best understood genitourinary neoplasms
      with a well defined etiology, natural history, tumor biology, treatment options
      and outcome. This level of understanding arises as a consequence of multiple
      factors and represents a convergence of knowledge from diverse scientific
      disciplines. Insight provided by these disciplines, coupled with unique features
      of this neoplasm which make it assessable for detection, monitoring and
      treatment, combine to make this disease a model system for modern oncology. The
      intent of this review is to provide the reader an overview of our current
      understanding of this tumor from the standpoint of its molecular biology as
      related to tumor development and progression.

PMID- 12507306
TI  - Molecular therapeutics in prostate cancer.
AB  - The purpose of this review is to provide information on the molecular basis of
      prostate cancer biology and to identify some of the targets for therapy, and
      highlight some potential strategies for molecular treatment. Here we give a
      synopsis of what we have learned regarding molecular biology of cancer in general
      and the directions research might take in the future in order to impact prostate
      cancer specifically. This work is certainly not encyclopedic in nature and we
      apologize in advance to colleagues whose work we were no able to include. Hope
      lies in learning to utilize some of these molecular workings for better
      prevention, diagnosis, and treatment of the most common solid organ cancer in
      men. Prostate cancer is a formidable disease and at current rates of diagnosis
      will affect one-in-six men living in the United States (Greenlee et al., 2000)
      Many of these men are diagnosed at an early stage of the disease and can be
      effectively treated by surgery or radiation. However, a significant fraction of
      men are diagnosed with later stage disease or progress despite early curative
      therapeutic attempts. Unfortunately, many of these men succumb to prostate
      cancer, as management options are limited and not always successful. Through an
      understanding of the molecular processes that occur in the development and
      progression of prostate cancer, novel therapies will arise that will provide
      longer survival, better quality of life, and a chance for cure in men afflicted
      with this disease.

PMID- 12507307
TI  - Expression and induction of anaphylatoxin C5a receptors in the rat liver.
AB  - The C5a-anaphylatoxin which is generated by limited proteolysis upon activation
      of the fifth component of complement may be induced by the classical, the
      alternative or the lectin pathway. C5a has been shown, under normal conditions,
      to induce the release of prostanoids from Kupffer cells (KC) and hepatic stellate
      cells (HSC) and thereby indirectly to increase glucose output from hepatocytes
      (HC). A direct action of C5a on HC would require the expression of the specific
      C5a receptor (C5aR). In studies using quantitative RT-PCR it was shown that non
      stimulated HC lack C5aR, in contrast to KC, HSC and sinusoidal endothelial cells
      (SEC) all of which contained mRNA for the C5aR in decreasing amounts. FACS
      analyses, immunohisto- and immunocytochemistry as well as functional analyses
      confirmed the results of the RT-PCR assays. Under inflammatory situations the
      C5aR was found to be upregulated in various organs and tissues which included the
      liver. Interleukin-6 (IL-6) as a main inflammatory mediator in the liver induced
      a de novo expression of functional C5aR in HC in-vitro and in-vivo. In contrast,
      LPS failed to induce C5aR directly in cultured HC in-vitro but induced C5aR in HC
      in vivo and in co-cultures of HC and KC which release IL-6 upon stimulation with
      LPS. So far, the only known effector function of C5a on HSC was the induction of
      prostanoid release. In an approach to reveal new functions of C5aR in HSC, the
      cells responsible for liver fibrosis, it could be shown that C5a upregulated
      fibronectin-specific mRNA five-fold whereas entactin, collagen IV and the
      structure protein smooth muscle actin were not affected. In addition, C5a did not
      upregulate specific mRNA for the profibrotic cytokine TGF-beta1 in either
      isolated KC or HSC. Thus, C5a alone appears to have only a limited role in the
      induction of liver fibrosis.

PMID- 12507308
TI  - Fate and functions of human adult lymphoid cells in immunodeficient mice.
AB  - Laboratory models enabling to study in vivo human leukocyte functions have been
      developed. Most of the models consist of human immunocytes transferred to mice
      homozygous for the scid mutation. Mice with additional immunodeficient-prone
      genetic background or with immunodeficiency-induced conditioning have also been
      used. Human grafts mainly consisted of human immune cells in suspension injected
      intraperitoneally, or in pieces of human organs containing immunocytes implanted
      subcutaneously. Cells in suspension could be easily manipulated in vitro before
      transfer to the animal, but disseminated within the mouse body. In opposition,
      human cells mostly remained within implantation areas of animals given human
      organ pieces. This favorizes cell interactions and helps for cell recovery after
      their in vivo passage. Moreover, the diversity of antibodies in animals
      transplanted with human lymphoid organ pieces appeared broader than that of mice
      transferred with lymphocytes in suspension. Spontaneous recall antibody and
      autoantibody productions have been generally observed in animals transferred with
      cells from donors with such antibodies. In vivo boosting of recall antibody by
      antigen has been most successful, but such a manipulation inconstantly boosted
      autoantibodies. Primary human T and B cell responses were difficult to obtain in
      xenochimeric animals, and success has been generally obtained by optimizing human
      immune response parameters, such as antigen presentation.

PMID- 12507309
TI  - Role of chromatin disruption and histone acetylation in thyroid hormone receptor
      action: implications in the regulation of HIV-1 LTR.
AB  - Thyroid hormone (TH) affects a wide variety of biological processes, from
      development to physiological function of different cells and organs. Alterations
      in plasma TH concentrations lead to developmental abnormalities and pathological
      consequences. Earlier studies have observed that plasma TH levels vary in AIDS
      patients such that low levels of TH correlate with survival rate. Furthermore,
      studies on the regulation of the human immunodeficiency virus type 1 (HIV-1) have
      shown that TH receptor (TR) is capable of binding to two regions within the long
      terminal repeat (LTR), which controls the transcription of HIV-1 genome. The frog
      oocyte is an in vivo system that allows microinjected DNA to be chromatinized in
      a process mimicking the process that occurs in somatic cells. Studies in the frog
      oocyte have provided in vivo evidence on the role of chromatin remodeling in
      transcriptional regulation by TR and have shown that TR utilizes similar
      mechanisms in the regulation of the HIV-1 LTR. That is, TR binds to LTR in
      chromatin in vivo and represses the LTR in the absence of TH by recruiting
      corepressor complexes containing histone deacetylases, and upon TH binding, TR
      causes chromatin remodeling and LTR activation.

PMID- 12507310
TI  - Modulating effect of respiration on atrioventricular conduction time assessed
      using PR interval variation.
AB  - Respiratory sinus arrhythmia (RSA) is the variation of heart rate (or RR
      interval) in phase with respiration and has been extensively studied. However,
      the effect of respiration on atrioventricular conduction delay (and hence PR
      interval length) has not yet received much attention. This work reports on
      measurements of respiration and associated RR and PR variability, in 11 subjects,
      assessed through surface electrocardiogram measurements, for both paced and
      spontaneous respiration in the supine position. A wavelet-based approach was used
      to extract RR and PR intervals. The accuracy of RR and PR interval measurement
      was consistent with previously published work. Respiratory atrioventricular
      conduction delay variability (RCV) was assessed using three techniques: spectral,
      peak-to-trough and cosinor methods. All measures showed statistically significant
      variations in PR interval due to respiration during paced respiration at 6 min(
      1). Of the three measures, cosinor analysis was most reliable in highlighting
      RCV. Using this measure, statistically significant RCV was seen in ten out of the
      11 subjects during paced respiration. The magnitude of the variability was
      estimated as +/- 5.9% of the mean PR interval. In spontaneous respiration,
      statistically significant RCV was seen in approximately half of the subjects,
      with an estimated variability of +/- 1.5%. As a control, statistically
      significant values for RSA were also obtained from the same data, which agreed
      with previously published measurements. It was concluded that respiration does
      indeed modulate atrioventricular conduction delay, deep breathing in the supine
      position accentuates this effect, and cosinor analysis provides a reliable means
      for quantifying this effect.

PMID- 12507311
TI  - Detection of asphyxia using heart rate variability.
AB  - The long-term aims of this study are to find a parameter derived from the ECG
      that has a high sensitivity and specificity to asphyxia and, once we know or
      suspect that asphyxia occurred, to estimate how severe it was. We carried out a
      pilot study in which 24 adult Wistar rats were anaesthetised and subjected to
      controlled asphyxia for specified durations. We measured the pH, 'neurological
      score' and the ECG, extracting from this heart rate and heart rate variability
      (HRV). We have developed a technique capable of detecting asphyxia in less than 1
      min, based on monitoring the ECG and estimating HRV by measuring the standard
      deviation of normal RR intervals (the RR interval is the time interval between
      two consecutive R-points of the QRS complex). In all cases the heart rate
      decreased and HRV increased, by an average of 46 +/- 33 ms in relation to the
      baseline, at the onset of asphyxia. The comparison of the base level of HRV after
      and before asphyxia shows promise for the estimation of the severity of the
      episode; however, the limitations of this study should be noted as they include
      the small size of the cohort and the methods of analysis.

PMID- 12507312
TI  - Automatic algorithm for filtering kinematic signals with impacts in the Wigner
      representation.
AB  - An automatic filtering algorithm is proposed for the accurate estimation of the
      second derivatives of kinematic signals with impacts. The impacts considered here
      occur when a moving object hits a rigid surface. The algorithm performs time
      frequency filtering in the Wigner representation, to deal efficiently with the
      non-stationarities caused by such impacts, and adjusts the parameters of its time
      frequency filtering function so that the filtering process adapts to the
      individual characteristics of the signal in hand. Performance analysis and
      comparative evaluation with experimentally acquired kinematic impact signals
      demonstrated a higher accuracy, with performance advantages over two widely used
      conventional automatic methods: linear phase autoregressive model-based
      derivative assessment (LAMBDA) and generalised cross-validation using quintic
      splines (GCVQS). For high impacts, the average absolute relative error in
      estimating the peak acceleration was 5.7% with the proposed method, 17.2% with a
      Butterworth low-pass filter optimised to yield minimum overall acceleration RMS
      error (best-case result), 18.3% with the LAMBDA method, and 37.2% with the GCVQS
      method. For signals with low impacts, the average absolute relative error was
      19.4%, 6.9%, 8.3% and 19.1%, respectively, in each case, which indicates that,
      for signals with a low-frequency content, there is no need for such time
      frequency filtering.

PMID- 12507313
TI  - Computerised visualisation from images of blood flow through frog mesenteric
      microvessels with multiple complexities.
AB  - Blood flow through a frog mesenteric microvessel, consisting of one loop and two
      successive bends, was recorded by a video-microscopic system and analysed by a PC
      based image processing system. After preprocessing, these images were analysed by
      the image velocimetry, axial tomography and image processing procedures. The
      blood flow in the microvessel had a Reynolds number of 0.033, and the Dean number
      varied from 0.004 in the loop to 0.007 in the bend, showing an increase in
      secondary flow in the bend region. These changes led to outward shifts in the
      peaks of velocity and concentration profiles, with an increase in the thickness
      of the outer walls (of about three times) compared with that of the inner walls.
      The mean velocity and mean cellular concentration showed a similar pattern. The
      variation in the cellular concentration in the microvessel was visualised by
      concentration contours and grey-scale images of the cellular distribution. At the
      inner wall of the complex geometry, the velocity reduced to zero, whereas the
      cellular concentration varied from 2 to 5%. In the high shear stress regions in
      the complex geometry, the vessel wall thickness was two-three times more than
      that in low shear stress regions.

PMID- 12507314
TI  - Periprosthetic modelling of femoral component fit using computed tomography data
      for total hip arthroplasty: a feasibility study.
AB  - The aim of the work was to create a new three-dimensional periprosthetic multi
      criteria optimisation technique to identify the best six degrees of freedom
      transform to position a porous-coated anatomic cementless femoral component for
      three factors, including: first, maximisation of the degree of contact achieved
      between designated bone ingrowth surfaces and the periprosthetic bone; secondly,
      minimisation of the bone mass to be removed to accommodate the component and
      thirdly, the extreme constraint of the component to be positioned so that it does
      not project beyond the periosteum. Discrete integrals were computed over regions
      of interest derived from the polyhedral component mesh in transaxial CT scan
      planes, using a polygon scan-conversion algorithm. A new biomedical imaging
      volume rendering technique utilising dynamic virtual textures was developed to
      visualise the design trade-offs. Pareto-optima were identified for four femora
      that matched an average-sized component. The non-linear, multi-modal fit metric
      was quadratic near minima, with a narrow trough of equivalent fit values within
      3mm of translation and 3 degrees of rotation with respect to the canal axis, and
      possessed a dependence most pronounced for distal-directed insertion against
      varus/valgus rotation. The study gives previously unavailable data on the three
      dimensional femoral component fit and is the first report that demonstrates that
      fitting the implant using several design criteria in a multi-criteria
      optimisation scheme is feasible.

PMID- 12507315
TI  - Accuracy of an optically isolated tetra-polar impedance measurement system.
AB  - Accurate electrical transfer impedance measurement at the high frequencies (> 1
      MHz) required to characterise blood and intracellular structures is very
      difficult, owing to stray capacitances between lead wires. To solve this problem,
      an optically isolated measurement system has been developed using a phase-locked
      loop technique for synchronisation between current injection (drive) and voltage
      measurement (receive) circuits. The synchronisation error between drive and
      receive circuits was less than 1 ns. The accuracy and reproducibility of the
      developed system was examined using a tissue equivalent Cole model consisting of
      two resistors and one capacitor. The absolute value Z and phase shift theta in
      impedance of the Cole model was measured at 1.25 MHz by both an LCR meter and the
      isolated measurement system. The difference between the values measured by the
      isolated measurement system and those measured by the LCR meter was less than
      0.27omega (2.9%) in Z and 0.79 degree in theta. The standard deviation was less
      than 0.09 omega in Z and 0.60 degree in theta.

PMID- 12507316
TI  - Body surface Laplacian mapping of atrial depolarization in healthy human
      subjects.
AB  - In the present study, we report body surface Laplacian mapping of atrial
      depolarization under sinus rhythm in 8 healthy male subjects. For each subject,
      95 unipolar disk electrodes with inter-electrode distance of 2 cm were used to
      record simultaneously potential ECGs over the anterior chest. The Laplacian ECG
      was then estimated during the P wave using a novel spline Laplacian technique.
      The body surface potential map (BSPM) and body surface Laplacian map (BSLM) at
      different time instants or time intervals of the P wave were constructed and
      compared. The present results showed that the BSPMs during the P wave were
      characterized by the rotation of a pair of positive/negative potential
      distribution from right to left around the anterior torso. On the other hand, the
      corresponding BSLMs revealed more spatial details, including two positive
      activities (denoted as P1 and P2, appeared in all 8 subjects), and three negative
      activities (denoted as N1, N2, and N3, appeared in 7, 7, and 4 subjects,
      respectively). The separation of these activities and their evolving patterns
      were also compared and confirmed by computer simulation using a realistic
      geometry heart-torso model. The above findings may be directly related to the
      underlying activation sequence during atrial depolarization in healthy subjects,
      suggesting the potential clinical applications of the Laplacian ECG technique.

PMID- 12507317
TI  - Cardiovascular response to dynamic aerobic exercise: a mathematical model.
AB  - An original mathematical model of the cardiovascular response to dynamic exercise
      is presented. It includes the pulsating heart, the pulmonary and systemic
      circulation, a separate description of the vascular bed in active tissues, the
      local metabolic vasodilation in these tissues and the mechanical effects of
      muscular contractions on venous return. Moreover, the model provides a
      description of the ventilatory response to exercise and various neural regulatory
      mechanisms working on cardiovascular parameters. These mechanisms embrace the so
      called central command, the arterial baroreflex and the lung inflation reflex.
      All parameters in the model have been given in accordance with physiological data
      from the literature. In this work, the model has been used to simulate the steady
      state value of the main cardiorespiratory quantities at different levels of
      aerobic exercise and the temporal pattern in the transient phase from rest to
      moderate exercise. Results suggest that, with suitable parameter values the model
      is able accurately to simulate the cardiorespiratory response in the overall
      range of aerobic exercise. This response is characterised by a moderate
      hypertension (10-30%) and by a conspicuous increase in systemic conductance (80
      130%), heart rate (64-150%) and cardiac output (100-200%). The transient pattern
      exhibits three distinct phases (lasting approximately 5s, 15s and 2 min), that
      reflect the temporal heterogeneity of the mechanisms involved. The model may be
      useful to improve understanding of exercise physiology and as an educational tool
      to analyse the complexity of cardiovascular and respiratory regulation.

PMID- 12507318
TI  - Touch-screen system for assessing visuo-motor exploratory skills in
      neuropsychological disorders of spatial cognition.
AB  - A new computerised test adopting touch-screen technology has been developed to
      assess the visuo-motor exploration of extra-personal space. The test was derived
      from well-known paper-and-pencil cancellation tasks used widely in the diagnosis
      and quantitative assessment of unilateral spatial neglect (USN), a
      neuropsychological syndrome that is more frequent and severe after damage to the
      right cerebral hemisphere. A main component deficit of USN is the defective visuo
      motor exploration of the side of space contralateral to the side of the lesion
      (contralesional), namely, in right-sided brain-damaged patients it occurs on the
      left side and vice versa. The computer-based paradigm consisted of a visuo-motor
      spatial exploratory task: the subjects were instructed to touch, in any order
      they wished, all the targets they detected on a computer touch-screen. This
      measured the time of occurrence and the spatial co-ordinates of each touch event
      and forwarded the data to the computer for storage; the computer provided
      feedback to the subject by 'tagging' the touched target. The paradigm allowed the
      calculation of accuracy and latency indexes and recorded the exploratory pathway
      taken by each subject. A pilot study was performed in ten normal subjects and 15
      brain-damaged patients, with and without psychometric evidence of USN; the
      results showed that the equipment was able to provide quantitative indexes
      related to the spatial-temporal aspects of exploratory ability, which are useful
      for diagnostic purposes, and revealed significant differences between the
      controls and patients with USN: the overall average values of latency and
      crossing indexes increased in patients with USN, compared with the controls
      (latency from 0.77 to 1.90s; path crossing index from 7.0% to 59.5%), and the
      significantly negative USN patient latency gradient (-2.79 against a null control
      value) evidenced a worsening of performance towards the left side.

PMID- 12507319
TI  - Comparison of laser speckle and laser Doppler perfusion imaging: measurement in
      human skin and rabbit articular tissue.
AB  - Laser Doppler perfusion imaging (LDI) is currently used in a variety of clinical
      applications, however, LDI instruments produce images of low resolution and have
      long scan times. A new optical perfusion imager using a laser speckle measurement
      technique and its use for in vivo blood flow measurements are described.
      Measurements of human skin and surgically exposed rabbit tissue made using this
      instrument were compared with a commercial laser Doppler perfusion imaging
      instrument. Results from blood flow measurements showed that the laser speckle
      imager measured an 11-67% decrease in blood flow under arterial occlusion. Under
      similar conditions, the laser Doppler imager measured blood flow decreases of 21
      63%. In comparison with LDI, it was observed that the higher temporal resolution
      of the laser speckle imager was more sensitive to measuring the hyperaemic
      response immediately following occlusion. This in vivo study demonstrated some of
      the several advantages laser speckle imaging has over conventional LDI, making
      the new instrument more versatile in a clinical environment.

PMID- 12507320
TI  - Inhibition of TNF-alpha induced cell death in human umbilical vein endothelial
      cells and Jurkat cells by protocatechuic acid.
AB  - The Chinese herb radix Salviae miltiorrhizae (RSM) is used in traditional Chinese
      medicine as a treatment for cardiovascular and cerebrovascular diseases. Several
      components of the plant extract from salvia mitorrhiza bunge have been determined
      previously, one of which is protocatechuic acid (PAC). It has been found, in the
      study, that PAC inhibited TNF-alpha-induced cell death of human umbilical vein
      endothelial cells (HUVECs) and Jurkat cells in a concentration of 100 microM when
      applied 2 h prior to TNF-alpha exposure. Molecular studies revealed that PAC
      activated NF-kappaB with a maximum effect after 30 min of treatment. Inhibition
      of NF-kappaB action by MG132 and NF-kappaB inhibitory peptide suppressed the cell
      protective effect of PAC. Further, degradation of IkBalpha occurred in response
      to PAC treatment. The results provide evidence that activation of NF-kappaB plays
      an important role in mediating the cell-protecting effect of PAC on HUVECs and
      Jurkat cells. Further studies are required to test whether PAC, a component of
      radix salviae miltiorrhizae, could be useful in preventing in vivo cell death
      resulting from cardiovascular or cerebrovascular diseases.

PMID- 12507321
TI  - Biosensor-controlled perfusion culture to estimate the viability of cells.
AB  - A perfusion cell culture is characterised by the continuous addition of fresh
      nutrient medium and the withdrawal of an equal volume of used medium, allowing
      the realisation of cell cultivation conditions that are approximated as closely
      as possible to the in vivo situation. The combination of a perfusion cell culture
      with an enzyme glucose biosensor allows the glucose consumption of the cell
      culture to be monitored continuously. The resulting biosensor-controlled
      perfusion cell culture is a complex biomonitoring system that is useful for
      checking the metabolic state of a perfusion cell culture continuously and non
      invasively over several days. With this experimental setup, it has been possible
      to test detrimental external effects on living systems at early stages, in vitro,
      but under in vivo-like conditions.

PMID- 12507322
TI  - Distribution of protein kinase C isoforms in the cat retina.
AB  - Immunocytochemical localization was carried out for five isoforms of protein
      kinase C (PKC) in the cat retina. In common with other mammalian species,
      PKCalpha was found in rod bipolar cells. Staining was also seen in a small
      population of cone bipolar cells with axon terminals ramifying near the middle of
      the inner plexiform layer (IPL). PKCbetaI was localized to rod bipolar cells, one
      class of cone bipolar cell, and numerous amacrine and displaced amacrine cells.
      Staining for PKCbetaI was seen in three types of cone bipolar cells as well as in
      amacrine and ganglion cells. Immunoreactivity for both PKCepsilon and PKCzeta was
      found in rod bipolar cells; PKCepsilon was also seen in a population of cone
      bipolar cells and a few amacrine and ganglion cells whereas PKCzeta was found in
      all ganglion cells. Double-label immunofluorescence studies showed that dendrites
      of the two PKCbetaII-positive OFF-cone bipolar cells exhibit immmunoreactivity
      for the kainate-selective glutamate receptor GluR5. The third PKCbetaII cone
      bipolar is an ON-type cell and did not stain for GluR5. The retinal distribution
      of these isoforms of PKC is consistent with a role in modulation of various
      aspects of neurotransmission including synaptic vesicle release and regulation of
      receptor molecules.

PMID- 12507323
TI  - AMPA glutamate receptor subunit 2 in normal and visually deprived macaque visual
      cortex.
AB  - Glutamate and its various receptors are known to play an important role in
      excitatory synaptic transmission throughout the CNS, including the primary visual
      cortex. Among subunits of the AMPA receptors (alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid), subunit 2 (GluR2) is of special significance because
      it controls their Ca2+ permeability. In the past, this subunit has been studied
      mostly in conjunction with other AMPA subunits. The present study sought to
      determine if GluR2 alone has a distinct laminar distribution in the normal
      macaque visual cortex, and if its pattern correlated with that of cytochrome
      oxidase (CO) under normal and monocularly deprived conditions. In the normal
      adult cortex, GluR2 immunoreactivity (ir) had a patchy distribution in layers
      II/III, in register with CO-rich puffs. GluR2-ir highlighted the upper border of
      layer II, the lower border of layer IV (previously termed IVC(beta dark)) and,
      most prominently, layer VI. Labeled neurons were primarily of the pyramidal type
      present in the upper border and lower half of layer VI, layers II/III, and
      scattered in layers V and upper IVB. Labeled nonpyramidal cells were large in
      layer IVB and small in IVC(beta dark). Notably, the bulk of CO-rich layers IVC
      and IVA had very low levels of GluR2-ir. At fetal day 13, however, GluR2 labeling
      showed a honeycomb-like pattern in layer IVA not found in the adult. A fragment
      of GluR2 cDNA was generated from a human cDNA library, and in situ hybridization
      revealed an expression pattern similar to that of GluR2 proteins. After 1-4 weeks
      of monocular impulse blockade with tetrodotoxin (TTX), alternating rows of strong
      and weak GluR2-ir in layers VI and II/III appeared in register with CO-labeled
      dark and light ocular dominance columns in layer IVC and puffs in II/III,
      respectively. Our results indicate that various cortical layers are
      differentially influenced by glutamate. The bulk of the major geniculate
      recipient layers IVC and IVA have low levels of GluR2, presumably favoring
      synaptic transmission via Ca(2+)-permeable glutamate receptors. GluR2 plays a
      more important role in supragranular and infragranular layers, where the initial
      geniculate signals are further modified and are transmitted to other cortical and
      subcortical centers. The maintenance of GluR2 in these output layers is governed
      by visual input and neuronal activity, as monocular impulse blockade induced a
      down-regulation of this subunit in deprived ocular dominance columns.

PMID- 12507324
TI  - Retinal ganglion cells projecting to the optic tectum and visual thalamus of
      lizards.
AB  - Retinal ganglion cells projecting to the optic tectum and visual thalamus have
      been investigated in the lizard, Podarcis hispanica. Injections of biotinylated
      dextran-amine in the optic tectum reveal seven morphological cell varieties
      including one displaced ganglion cell type. Injections in the visual thalamus
      yield similar ganglion cell classes plus four giant ganglion cells, including two
      displaced ganglion cell types. The present study constitutes the first comparison
      of tectal versus thalamic ganglion cell types in reptiles. The situation found in
      lizards is similar to that reported in mammals and birds where some cell types
      projecting to the thalamus are larger than those projecting to the mesencephalic
      roof. The presence of giant retino-thalamic ganglion cells with specific
      dendritic arborizations in sublaminae A and B of the inner plexiform layer
      suggests that parts of the visual thalamus of lizards could be implicated in
      movement detection, a role that might be played by the ventral lateral geniculate
      nucleus, which is involved in our tracer injections.

PMID- 12507325
TI  - Feedback from V1 and inhibition from beyond the classical receptive field
      modulates the responses of neurons in the primate lateral geniculate nucleus.
AB  - It is well established that the responses of neurons in the lateral geniculate
      nucleus (LGN) can be modulated by feedback from visual cortex, but it is still
      unclear how cortico-geniculate afferents regulate the flow of visual information
      to the cortex in the primate. Here we report the effects, on the gain of LGN
      neurons, of differentially stimulating the extraclassical receptive field, with
      feedback from the striate cortex intact or inactivated in the marmoset monkey,
      Callithrix jacchus. A horizontally oriented grating of optimal size, spatial
      frequency, and temporal frequency was presented to the classical receptive field.
      The grating varied in contrast (range: 0-1) from trial to trial, and was
      presented alone, or surrounded by a grating of the same or orthogonal
      orientation, contained within either a larger annular field, or flanks oriented
      either horizontally or vertically. V1 was ablated to inactivate cortico
      geniculate feedback. The maximum firing rate of LGN neurons was greater with V1
      intact, but was reduced by visually stimulating beyond the classical receptive
      field. Large horizontal or vertical annular gratings were most effective in
      reducing the maximum firing rate of LGN neurons. Magnocellular neurons were most
      susceptible to this inhibition from beyond the classical receptive field.
      Extraclassical inhibition was less effective with V1 ablated. We conclude that
      inhibition from beyond the classical receptive field reduces the excitatory
      influence of V1 in the LGN. The net balance between cortico-geniculate excitation
      and inhibition from beyond the classical receptive field is one mechanism by
      which signals relayed from the retina to V1 are controlled.

PMID- 12507326
TI  - Circadian rhythms of dopamine in mouse retina: the role of melatonin.
AB  - Both dopamine and melatonin are important for the regulation of retinal
      rhythmicity, and substantial evidence suggests that these two substances are
      mutually inhibitory factors that act as chemical analogs of day and night. A
      circadian oscillator in the mammalian retina regulates melatonin synthesis. Here
      we show a circadian rhythm of retinal dopamine content in the mouse retina, and
      examine the role of melatonin in its control. Using high-performance liquid
      chromatography (HPLC), we measured levels of dopamine and its two major
      metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA),
      in retinas of C3H+/+ mice (which make melatonin) and C57BL/6J mice that are
      genetically incapable of melatonin synthesis. In a light/dark cycle both strains
      of mice exhibited daily rhythms of retinal dopamine, DOPAC, and HVA content.
      However, after 10 days in constant darkness (DD), a circadian rhythm in dopamine
      levels was present in C3H, but not in C57 mice. C57 mice given ten daily
      injections of melatonin in DD exhibited a robust circadian rhythm of retinal
      dopamine content whereas no such rhythm was present in saline-injected controls.
      Our results demonstrate that (1) a circadian clock generates rhythms of dopamine
      content in the C3H mouse retina, (2) mice lacking melatonin also lack circadian
      rhythms of dopamine content, and (3) dopamine rhythms can be generated in these
      mice by cyclic administration of exogenous melatonin. Our results also indicate
      that circadian rhythms of retinal dopamine depend upon the rhythmic presence of
      melatonin, but that cyclic light can drive dopamine rhythms in the absence of
      melatonin.

PMID- 12507327
TI  - Experimental retinal detachment in the cone-dominant ground squirrel retina:
      morphology and basic immunocytochemistry.
AB  - The cellular responses of the cone-dominant ground squirrel retina to retinal
      detachment were examined and compared to those in rod-dominant species. Retinal
      detachments were made in California ground squirrels. The retinas were prepared
      for light, electron, and confocal microscopy. Tissue sections were labeled with
      antibodies to cone opsins, rod opsin, glial fibrillary acidic protein (GFAP),
      vimentin, synaptophysin, cytochrome oxidase, and calbindin D 28K. Wax sections
      were probed with the MIB-1 antibody to detect proliferating cells. By 10 h
      postdetachment many photoreceptor cells in the ground squirrel already show
      structural signs of apoptosis. At 1 day many photoreceptors have collapsed inner
      segments (IS), yet others still have short stacks of outer segment discs. At 3
      days there is a marked increase in the number of dying photoreceptors. Rod and
      medium-/long-wavelength opsins are redistributed in the cell membrane to their
      synaptic terminals. At 7 days photoreceptor cell death has slowed. Some regions
      of the outer nuclear layer (ONL) have few photoreceptor somata. IS remnants are
      rare on surviving photoreceptors. At 28 days these trends are even more dramatic.
      Retinal pigmented epithelium (RPE) cells do not expand into the subretinal space.
      The outer limiting membrane (OLM) appears flat and uninterrupted. Muller cells
      remain remarkably unreactive; they show essentially no proliferation, only
      negligible hypertrophy, and there is no increase in their expression of GFAP or
      vimentin. Horizontal cells show no dendritic sprouting in response to detachment.
      The speed and extent of photoreceptor degeneration in response to detachment is
      greater in ground squirrel than in cat retina-only a small number of rods and
      cones survive at 28 days of detachment. Moreover, the almost total lack of Muller
      cell and RPE reactivity in the ground squirrel retina is a significant difference
      from results in other species.

PMID- 12507328
TI  - Dynamic changes in the receptive fields of L1-type horizontal cells in the retina
      of the turtle Mauremys caspica.
AB  - The resistances of the horizontal cell syncytium in the vertebrate retina are
      modulated in a time-dependent fashion during light stimulation. Therefore, the
      spatial properties of horizontal cells are expected to change with time after the
      illumination conditions are altered. This study was designed to investigate time-
      and intensity-dependent changes in the receptive-field properties of L1-type
      horizontal cells in the turtle Mauremys caspica. Photoresponses were elicited by
      monochromatic (650 nm) light stimuli of 2-s duration covering retinal spots of
      different radii. The length constants were derived from the relationships between
      amplitude and spot radius that were constructed for different time intervals
      after onset of the light stimulus. For a given stimulus intensity, the length
      constant transiently increased to a peak value and then slowly recovered to a
      plateau level. When the length constant was compared to the amplitude of the
      response to full-field illumination for the entire duration of the light
      stimulus, an ellipse-like curve was obtained indicating that for a given membrane
      potential, two different values of the length constant could be obtained.
      Dopamine considerably reduced the size of the receptive fields but did not affect
      the time-dependent changes in the length constant. These results indicate that
      changes in the membrane resistance underlie short-term modulation of the
      receptive-field properties of turtle L1-type horizontal cells after onset of a
      light stimulus.

PMID- 12507329
TI  - Expression of MARCKS mRNA in lateral geniculate nucleus and visual cortex of
      normal and monocularly deprived macaque monkeys.
AB  - We performed a nonradioactive in situ hybridization histochemistry (ISH) study of
      the lateral geniculate nucleus (LGN) and the primary visual area (area 17) of the
      macaque monkey to investigate mRNA expression of the myristoylated alanine-rich C
      kinase substrate (MARCKS), a major protein kinase C (PKC) substrate. In the LGN,
      intense hybridization signals were observed in both magnocellular neurons (layers
      1 and 2) and parvocellular neurons (layers 3 to 6). Double labeling using ISH and
      immunofluorescence revealed that MARCKS mRNA was coexpressed with the alpha
      subunit of type II calcium/calmodulin-dependent protein kinase, indicating that
      MARCKS mRNA is also expressed in koniocellular neurons in the LGN. GABA
      immunoreactive neurons in the LGN did not contain MARCKS mRNA, indicating that
      MARCKS mRNA is not expressed in inhibitory interneurons. The signals were
      generally weak in area 17, and intense signals were restricted to large neurons
      in layers IVB, V, and VI. GABA-immunoreactive neurons in layers II-VI of area 17
      did not contain MARCKS mRNA. Double-label ISH revealed that MARCKS mRNA was
      coexpressed with mRNA of GAP-43, another PKC substrate, in neurons of both the
      LGN and area 17. To determine whether the expression of MARCKS mRNA is regulated
      by retinal activity, we performed ISH in the LGN and area 17 of monkeys deprived
      of monocular visual input by tetrodotoxin. After monocular deprivation for 5 to
      30 days, MARCKS mRNA was down-regulated in the LGN, but not in area 17. These
      results suggest that MARCKS mediates the activity-dependent changes in the
      excitatory relay neurons in the LGN.

PMID- 12507330
TI  - Contrast adaptation in retinal and cortical evoked potentials: no adaptation to
      low spatial frequencies.
AB  - Contrast adaptation occurs in both the retina and the cortex. Defining its
      spatial dependence is crucial for understanding its potential roles. We thus
      asked to what degree contrast adaptation depends on spatial frequency, including
      cross-adaptation. Measuring the pattern electroretinogram (PERG) and the visual
      evoked potential (VEP) allowed separating retinal and cortical contributions. In
      ten subjects we recorded simultaneous PERGs and VEPs. Test stimuli were
      sinusoidal gratings of 98% contrast with spatial frequencies of 0.5 or 5.0 cpd,
      phase reversing at 17 reversals/s. Adaptation was controlled by prolonged
      presentation of these test stimuli or homogenous gray fields of the same
      luminance. When adaptation and test frequency were identical, we observed
      significant contrast adaptation only at 5 cpd: an amplitude reduction in the PERG
      (-22%) and VEP (-58%), and an effective reduction of latency in the PERG (-0.95
      ms). When adapting at 5 cpd and testing at 0.5 cpd, the opposite effect was
      observed: enhancement of VEP amplitude by +26% and increase in effective PERG
      latency by + 1.35 ms. When adapting at 0.5 cpd and testing at 5 cpd, there was no
      significant amplitude change in PERG and VEP, but a small effective PERG latency
      increase of +0.65 ms. The 0.5-cpd channel was not adapted by spatial frequencies
      of 0.5 cpd. The adaptability of the 5-cpd channel may mediate improved detail
      recognition after prolonged blur. The existence of both adaptable and
      nonadaptable mechanisms in the retina allows for the possibility that by
      comparing the adaptational state of spatial-frequency channels the retina can
      discern between overall low contrast and defocus in emmetropization control.

PMID- 12507331
TI  - On the velocity tuning of area 18 complex cell responses to moving textures.
AB  - Unlike simple cells, complex cells of area 18 give a directionally selective
      response to motion of random textures, indicating that they may play a special
      role in motion detection. We therefore investigated how texture motion, and
      especially its velocity, is represented by area 18 complex cells. Do these cells
      have separable spatial and temporal tunings or are these nonseparable? To answer
      this question, we measured responses to moving random pixel arrays as a function
      of both pixel size and velocity, for a set of 63 directionally selective complex
      cells. Complex cells generally responded to a fairly wide range of pixel sizes
      and velocities. Variations in pixel size of the random pixel array only caused
      minor changes in the cells' preferred velocity. For nearly all cells the data
      much better fitted a model in which pixel size and velocity act separately, than
      a model in which pixel size and velocity interact so as to keep temporal
      frequency sensitivity constant. Our conclusion is that the studied population of
      special complex cells in area 18 are true motion detectors, rather than temporal
      frequency tuned neurons.

PMID- 12507332
TI  - Axonal regeneration of retinal ganglion cells after optic nerve pre-lesions and
      attachment of normal or pre-degenerated peripheral nerve grafts.
AB  - Axonal regeneration of retinal ganglion cells (RGCs) into a normal or pre
      degenerated peripheral nerve graft after an optic nerve pre-lesion was
      investigated. A pre-lesion performed 1-2 weeks before a second lesion has been
      shown to enhance axonal regeneration in peripheral nerves (PN) but not in optic
      nerves (ON) in mammals. The lack of such a beneficial pre-lesion effect may be
      due to the long delay (1-6 weeks) between the two lesions since RGCs and their
      axons degenerate rapidly 1-2 weeks following axotomy in adult rodents. The
      present study examined the effects of the proximal and distal ON pre-lesions with
      a shortened delay (0-8 days) on axonal regeneration of RGCs through a normal or
      pre-degenerated PN graft. The ON of adult hamsters was transected intraorbitally
      at 2 mm (proximal lesion) or intracranially at 7 mm (distal lesion) from the
      optic disc. The pre-lesioned ON was re-transected at 0.5 mm from the disc after
      0, 1, 2, 4, or 8 days and a normal or a pre-degenerated PN graft was attached
      onto the ocular stump. The number of RGCs regenerating their injured axons into
      the PN graft was estimated by retrograde labeling with FluoroGold 4 weeks after
      grafting. The number of regenerating RGCs decreased significantly when the delay
      time increased in animals with both the ON pre-lesions (proximal or distal)
      compared to control animals without an ON pre-lesion. The proximal ON pre-lesion
      significantly reduced the number of regenerating RGCs after a delay of 8 days in
      comparison with the distal lesion. However, this adverse effect can be overcome,
      to some degree, by a pre-degenerated PN graft applied 2, 4, or 8 days after the
      distal ON pre-lesion enhanced more RGCs to regenerate than the normal PN graft.
      Thus, in order to obtain the highest number of regenerating RGCs, a pre
      degenerated PN should be grafted immediately after an ON lesion.

PMID- 12507333
TI  - The representation of the ipsilateral eye in nucleus isthmi of the leopard frog,
      Rana pipiens.
AB  - The retina of the leopard frog projects topographically to the superficial
      neuropil of the entire contralateral tectum. In the rostromedial neuropil of the
      tectum, there is a map of the binocular region of the visual field seen from the
      ipsilateral eye that is in register with the map of the binocular region of the
      visual field seen from the contralateral eye. The ipsilateral eye projects
      indirectly to the tectum through nucleus isthmi (n. isthmi), a midbrain tegmental
      structure. N. isthmi receives input from the ipsilateral optic tectum and sends
      projections bilaterally that cover both tectal lobes. Previous workers have not
      been able to find visual activity from the ipsilateral eye in the caudolateral
      optic tectum, representing the monocular visual field of the contralateral eye.
      We show electrophysiologically that across the entire extent of n. isthmi there
      are two superimposed maps, one map representing the entire visual field of the
      contralateral eye, the other map representing the binocular visual field of the
      ipsilateral eye. We also studied the behavioral consequences of localized lesions
      to n. isthmi and compared them to the behavioral consequences of localized
      lesions to the optic tectum representing equivalent areas of the visual field.
      Lesions to the optic tectum produce scotomas in the corresponding portion of the
      visual field. Lesions to n. isthmi, even medial n. isthmi representing the
      superior visual field, lead to scotomas in the temporal-most portion of the
      contralateral ground level visual field. Thus, the representation of visual space
      in n. isthmi is not a simple copy of the tectal representation of visual space.

PMID- 12507334
TI  - Localization of kainate receptors to the presynaptic active zone of the rod
      photoreceptor in primate retina.
AB  - Visual information is encoded at the photoreceptor synapse by modulation of the
      tonic release of glutamate from one or more electron-dense ribbons. This release
      is highest in the dark, when photoreceptors are depolarized, and decreases in
      grades when photoreceptors hyperpolarize with increasing light. Functional
      diversity between neurons postsynaptic at the synaptic ribbon arises in part from
      differential expression of both metabotropic (G-protein-gated) and ionotropic
      (ligand-gated) glutamate receptor. In the brain, different subunits also modulate
      the presynaptic active zone. In hippocampus, ionotropic kainate receptors
      localize to the presynaptic membrane of glutamatergic axon terminals and
      facilitate depolarization of the synapse (e.g. Lauri et al., 2001). Such
      facilitation may be helpful in the retina, where consistent depolarization of the
      photoreceptor axon terminal is necessary to maintain glutamate release in the
      dark. We investigated whether such a mechanism could be present in primate retina
      by using electron microscopy to examine the localization of the kainate subunits
      GluR6/7 at the rod axon terminal, where only a single ribbon synapse mediates
      glutamate release. We scored 54 rod axon terminals whose postsynaptic space
      contained one or more GluR6/7-labeled processes and traced these processes
      through serial sections to determine their identity. Of 68 labeled processes, 63%
      originated from narrow "fingers" of cytoplasm extending from the presynaptic axon
      terminal into the postsynaptic cleft. Each rod terminal typically inserts 4-6
      presynaptic fingers, and we scored several instances where multiple fingers
      contained label. Such consistency suggests that each presynaptic finger expresses
      GluR6/7. The physiological properties of kainate receptors and the geometry of
      the rod axon terminal suggest that presynaptic GluR6/7 could provide a steady
      inward current to maintain consistent depolarization of the rod synapse in the
      long intervals between photons in the dark.

PMID- 12507335
TI  - Method for the analysis of posture and interface pressure of car drivers.
AB  - Biomechanical study of car driver posture is one of the most referenced aspects
      for the ergonomic design process of the whole vehicle. The aim of this work is to
      present a multi-factor method for the analysis of sitting posture and the
      resulting interactions of the car driver body with the cushion and the backrest.
      The proposed method, based on the combined use of an optoelectronic system for
      motion capture and suitable matrices of pressure sensors, has allowed the
      measurement of a large set of car driver posture parameters and the
      identification of specific sitting strategies characterising the driving posture,
      despite the different behaviours of the analysed subjects.

PMID- 12507336
TI  - An analysis of the forces required to drag sheep over various surfaces.
AB  - Some occupational health and safety hazards associated with sheep shearing are
      related to shearing shed design. One aspect is the floor of the catching pen,
      from which sheep are caught and dragged to the shearing workstation. Floors can
      be constructed from various materials, and may be level or gently sloping. An
      experiment was conducted using eight experienced shearers as participants to
      measure the force exerted by a shearer when dragging a sheep. Results showed that
      significant changes in mean dragging force occurred with changes in both surface
      texture and slope. The mean dragging forces for different floor textures and
      slopes ranged from 359 N (36.6 kg) to 423N (43.2 kg), and were close to the
      maximum acceptable limits for pulling forces for the most capable of males. The
      best floor tested was a floor sloped at 1:10 constructed of timber battens
      oriented parallel to the path of the drag, which resulted in a mean dragging
      force 63.6N (15%) lower than the worst combination.

PMID- 12507337
TI  - A method for evaluation of manual work using synchronised video recordings and
      physiological measurements.
AB  - Industrial interventions that focus on increased productivity may impair the
      ergonomics, on a workstation or individual level. This paper presents a method
      that characterises work time consumption and physical work load of manual work,
      using video recordings synchronised with physiological measurements of, e.g.
      muscular activity, and postures. The underlying idea was that it is possible to
      amalgamate technical and human aspects resulting in a synergetic evaluation. The
      method was developed through two case studies within the Swedish automotive
      industry, where manual materials handling was studied. A methodological result
      was that the synchronising procedure was sufficiently precise to allow work
      activities to be assigned significantly different levels of physical work load.
      These different levels may be used to predict physical work load in the design
      and change of production systems. It was concluded that the method is accurate
      enough to be a useful tool in industrial interventions.

PMID- 12507338
TI  - A triaxial accelerometer for measuring arm movements.
AB  - A triaxial accelerometer used as an inclinometer (INC) (Logger Technology,
      Sweden) needed to be evaluated for field measurements of arm postures and
      movements. INC consists of one portable data logger and up to four sensors. Each
      sensor measures the inclination to the vertical line. The sampling frequency is
      20 Hz and, the logger can collect data for up to 12 h. The aim of the present
      study was to compare INC measurements with those from an optoelectronic measuring
      system- the Mac Reflex system (OPT) (Qualisys AB, Sweden). For all movements with
      normal to high velocities INC measured the degree of arm elevation with very high
      precision. At very high velocities and, especially when the direction of the
      velocity was perpendicular to the vertical line the largest differences between
      INC and OPT were found. In field studies INC has proved to be very safe and
      useful in assessment of arm movements. INC was easy to handle and easy to wear
      for the researcher and the subject, respectively.

PMID- 12507339
TI  - Restoring the order: gender segregation as an obstacle to organisational
      development.
AB  - This paper raises questions about the links between gender and organisational
      changes. The empirical base for the discussion is a qualitative study of the
      effects of organisational changes in the pulp and paper industry, the electronics
      industry, the food industry and the laundry industry in Sweden during the mid
      1990s. At the studied companies, restoration responses in the work organisations
      brought the organisation back into its original form and function. The study
      shows that gender exerts an influence both on the existing work organisation and
      in the organisational change. The modern organisation, with its focus on
      integration and decentralisation, challenges the gender order, which is a strong
      system, built on segregation and hierarchy. The conclusion from the study is that
      gender segregating and stereotypic gender-coding of workplaces and work tasks
      were strong restoring mechanisms and obstacles to strategic organisational
      changes.

PMID- 12507340
TI  - Using virtual reality technology for aircraft visual inspection training:
      presence and comparison studies.
AB  - The aircraft maintenance industry is a complex system consisting of several
      interrelated human and machine components. Recognizing this, the Federal Aviation
      Administration (FAA) has pursued human factors related research. In the
      maintenance arena the research has focused on the aircraft inspection process and
      the aircraft inspector. Training has been identified as the primary intervention
      strategy to improve the quality and reliability of aircraft inspection. If
      training is to be successful, it is critical that we provide aircraft inspectors
      with appropriate training tools and environment. In response to this need, the
      paper outlines the development of a virtual reality (VR) system for aircraft
      inspection training. VR has generated much excitement but little formal proof
      that it is useful. However, since VR interfaces are difficult and expensive to
      build, the computer graphics community needs to be able to predict which
      applications will benefit from VR. To address this important issue, this research
      measured the degree of immersion and presence felt by subjects in a virtual
      environment simulator. Specifically, it conducted two controlled studies using
      the VR system developed for visual inspection task of an aft-cargo bay at the VR
      Lab of Clemson University. Beyond assembling the visual inspection virtual
      environment, a significant goal of this project was to explore subjective
      presence as it affects task performance. The results of this study indicated that
      the system scored high on the issues related to the degree of presence felt by
      the subjects. As a next logical step, this study, then, compared VR to an
      existing PC-based aircraft inspection simulator. The results showed that the VR
      system was better and preferred over the PC-based training tool.

PMID- 12507341
TI  - Effect of the number of two-wheeled containers at a gathering point on the
      energetic workload and work efficiency in refuse collecting.
AB  - The effect of the number of two-wheeled containers at a gathering point on the
      energetic workload and the work efficiency in refuse collecting was studied in
      order to design an optimal gathering point for two-wheeled containers. Three
      sizes of gathering points were investigated, i.e. with 2, 16 and 32 two-wheeled
      containers at a gathering point. The collecting of two-wheeled containers was
      simulated in a test circuit. The energetic workload was quantified by the
      parameters oxygen uptake (1 min(-1)), heart rate (beats min(-1)) and perceived
      exertion. The work efficiency was quantified as the time it took to collect 32
      two-wheeled containers per time period. The maximum acceptable amount of two
      wheeled containers collected during an 8-h working day was estimated using the
      energetic criterion of a maximum oxygen uptake of 30% VO2max. The size of the
      gathering point had no effect on the oxygen uptake, heart rate or perceived
      exertion. However, the number of two-wheeled containers per collecting period
      (work efficiency) and the maximum acceptable amount during an 8-h working day
      were higher in the conditions with 16 and 32 two-wheeled containers at a
      gathering point compared to the condition with the 2 two-wheeled containers at a
      gathering point.

PMID- 12507342
TI  - Anthropometric survey of Indian farm workers to approach ergonomics in
      agricultural machinery design.

PMID- 12507343
TI  - The anthropometric database for children and young adults in Taiwan.

PMID- 12507344
TI  - The Behavior Change Consortium studies: missed opportunities--individual focus
      with an inadequate engagement with personhood and socio-economic realities.

PMID- 12507345
TI  - Response to Connelly. First at the Gates of Fire: can there be any survivors?

PMID- 12507346
TI  - Human papillomavirus infections and risks of cervical cancer: what do women know?
AB  - Human papillomavirus (HPV) is now known to be a risk factor for the development
      of cervical cancer. This study examines women's knowledge of cervical screening
      and dysplasia and HPV. The entire female work force of a medium-sized UK
      university received a questionnaire concerning knowledge of cervical screening,
      treatment for abnormalities and HPV. Four hundred women returned completed
      questionnaires. Knowledge of early cervical cancer detection and screening
      methods was good. However, risk factors for cervical cancer were not well known.
      Awareness and knowledge of HPV was very limited. Past experience of an abnormal
      smear result and colposcopy was significantly associated with good knowledge of
      cervical screening, but not with knowledge of HPV. It is essential to improve
      women's understanding of this area in the context of plans to include screening
      for HPV in the UK's national cervical screening programme.

PMID- 12507347
TI  - Current action for skin cancer risk reduction in English schools: pupils'
      behaviour in relation to sunburn.
AB  - In a random sample of schools distributed throughout all areas of England, 2703
      primary school pupils from 46 schools and 2692 secondary school pupils from 32
      schools were surveyed regarding behaviour in the sun, and opinions and experience
      of sunburn. Seventy percent (1879) of primary and 36.5% (982) of secondary pupils
      recalled hearing about protecting themselves from the sun at school. Primary
      school pupils who recalled they were told to 'stay in the shade' were more likely
      say they did so; 27.3% (739) of primary and 20.7% (556) of secondary school
      pupils reported getting sunburnt; and 53.2% (393/739) primary school pupils and
      52.5% (292/556) secondary school pupils reporting sunburn said their sunburn
      peeled. The most common time both primary and secondary pupils said they got
      sunburnt at school was at lunchtime (mid-day break); the next most common time
      was during sports day. Pupils saying they did not protect their skin because they
      wanted a tan were more likely to report sunburn (41.7% primary and 29.5%
      secondary) than those giving other reasons. Primary school pupils who said they
      used sun screen frequently (285/847) were more likely than 'never users'
      (178/813) to report sunburn, as were secondary school pupils (53/192 and 264/1565
      for frequent and 'never users', respectively). Dark- and light-skinned pupils at
      primary school (27.3 and 27.4%, respectively) were equally likely to say they had
      been sunburnt. At secondary school, only 10.6% of dark-skinned compared with
      22.3% of light-skinned pupils reported sunburn. The last two findings might be
      related to cultural behaviours and are discussed later. Pupils of all ages need
      encouragement to protect their skin at mid-day break, to use sunscreens correctly
      and be aware of alternative sun-protection methods. Education is needed which
      challenges the notion that a 'tan is beautiful' and uses social teaching methods
      to empower pupils to carry out sun protection in real life.

PMID- 12507348
TI  - Factor structure of the School Well-being Model.
AB  - The aim of this study was to confirm empirically the factor structure of the
      School Well-being Model. In this Model well-being was divided into school
      conditions, social relationships, means for self-fulfillment and health status.
      Data for this study were collected by the School Health Promotion Survey in
      Finland with 40147 respondents from Grades 8 and 9. The 43 variables from the
      Survey were fitted into the School Well-being Model using confirmatory factor
      analysis. The Goodness of Fit Index (GFI) for the four-factor model was 0.93 and
      GFI Adjusted for Degrees of Freedom was 0.93. The correlations between factors
      varied from 0.30 to 0.78 and internal consistencies (Cronbach's alphas) from 0.62
      to 0.84. The categories school conditions and health status had a good variety of
      variables. However, the social relationships and the means for self-fulfillment
      categories would have benefited from additional questions. The School Well-being
      Model can be utilized to construct school well-being profiles both for groups of
      pupils and for schools as a whole. The school well-being profile could highlight
      the area or areas in which schools could make improvements in order to promote
      the well-being of its pupils.

PMID- 12507349
TI  - Can motivational signs prompt increases in incidental physical activity in an
      Australian health-care facility?
AB  - This study aimed to evaluate whether a stair-promoting signed intervention could
      increase the use of the stairs over the elevator in a health-care facility. A
      time-series design was conducted over 12 weeks. Data were collected before,
      during and after displaying a signed intervention during weeks 4-5 and 8-9.
      Evaluation included anonymous counts recorded by an objective unobtrusive motion
      sensing device of people entering the elevator or the stairs. Self-report data on
      stair use by hospital staff were also collected. Stair use significantly
      increased after the first intervention phase (P = 0.02), but after the
      intervention was removed stair use decreased back towards baseline levels.
      Moreover, stair use did not significantly change after the re-introduction of the
      intervention. Lastly, stair use decreased below the initial baseline level during
      the final weeks of evaluation. Furthermore, there was no significant change in
      self-reported stair use by hospital staff. Therefore, the signed intervention
      aimed at promoting an increase in incidental physical activity produced small
      brief effects, which were not maintained. Further research is required to find
      more effective 'point of choice' interventions to increase incidental physical
      activity participation with more sustainable impact.

PMID- 12507350
TI  - Factors associated with smoking progression among Spanish adolescents.
AB  - Smoking onset takes place in the early years of adolescence, and can be seen as a
      progression through stages of preparation, trying, experimentation, regular
      smoking and nicotine dependence or addiction. The objective of this study is to
      identify 1-year predictors of smoking consolidation among occasional smokers
      (experimenters) and of cessation among all smokers. A questionnaire developed to
      monitor trends in smoking and other health-related behaviors was administered in
      the spring of 1992 and again 1 year later (1993). The survey was carried out in
      six large, private schools in Barcelona and Raimat, in the Lleida province, in
      Catalonia (Spain). In total, 1460 schoolchildren aged 12-19 responded to both the
      baseline and follow-up questionnaires; 1236 questionnaires (84.7%) were matched
      through a personal code and were used for the longitudinal study. At the baseline
      survey 28% of the schoolchildren were regular smokers and 17.1 % were occasional
      smokers, with no differences by gender. At the follow-up survey, progression from
      occasional to regular smoking was observed in 42% of the girls and 22.7% of the
      boys. Other predictors of consolidation included drinking alcohol (OR = 3.1; 95%
      CI = 1.1-10.1) and reporting the intention to smoke in the future (OR = 2.5; 95%
      CI = 1.3-4.9). Among all the smokers at the baseline, predictors of cessation
      were smoking occasionally (versus regularly) (OR = 4.9; 95% CI = 2.8-8.6),
      negative attitudes regarding smoking (OR = 3.3; 95% CI = 1.9-5.4), reporting no
      intention to smoke in the future (OR = 2.2; 95% CI = 1.3-3.8), gender (OR for
      boys = 2.1; 95% CI = 1.2-3.6), receiving weekly pocket less than 1000 ptas (OR =
      1.7; 95% CI = 1.1-5.3) and age (OR for being 15 and younger = 1.6; 95% CI = 1.1
      4.9). We conclude that consolidation of smoking is twice as likely among girls
      than among boys. Intention to smoke seems to be a good predictor of future
      behavior, while attitudes may predict cessation, but not consolidation. Available
      pocket money seems to be a strong risk factor for smoking at this age.

PMID- 12507351
TI  - An intervention for the promotion of hygienic feces disposal behaviors in a
      shanty town of Lima, Peru.
AB  - This paper describes the design, implementation and evaluation of an intervention
      to promote improved hygiene practices in a shanty town area of Lima, Peru.
      Following formative research, the intervention focused on behaviors associated
      with the hygienic use of potties by children aged 15-47 months and keeping the
      home environment free from feces. A health communications strategy was developed
      involving delivery through routine health services, and using video
      presentations, leaflets and counseling by health staff during consultations.
      Intervention activities occurred during a 6-month period in health centers and
      posts of four intervention communities; four other communities acted as a
      comparison group. Process and impact indicators were measured through
      questionnaires and 4-h structured observations conducted in over 600 households
      both pre- and post-intervention implementation, and through intervention
      monitoring activities. The intervention materials and approach were well received
      by the study community; however, in the time-frame of the project only limited
      coverage of the target audience was achieved, which was insufficient to result in
      an impact on behaviors. Nevertheless sufficient positive features existed to
      suggest that with higher coverage, an impact on target behaviors might have been
      achieved. Reasons for the intervention's shortcomings are discussed and
      suggestions made for more effective implementation.

PMID- 12507352
TI  - Motivation in later life: personal projects and well-being.
AB  - "Personal projects," as defined by B. R. Little (1983), were elicited from 600
      community residents aged 70+, representing a broad range of health and illness.
      Factor analysis revealed 6 types of personal projects: activities of daily
      living, active recreation, other-oriented activities, intellectual activities,
      home planning, and spiritual moral activities. Background factors and health were
      shown to affect the number and type of projects reported. Most indices of
      personal projects were associated with positive affect and valuation of life.
      Only 1 was associated with depression. This confirms the differential association
      of personal projects to positive but not negative affect. Personal projects are
      seen as part of an open motivational system in which social position, cognitive
      ability, health, and positive mental health are mutually interacting members.

PMID- 12507353
TI  - The role of cognitive stimulation on the relations between age and cognitive
      functioning.
AB  - To make a convincing argument that cognitive stimulation moderates age trends in
      cognition there must be (a) a negative relation between age and level of
      cognitive stimulation, (b) a positive relation between level of cognitive
      stimulation and level of cognitive functioning, and (c) evidence of an
      interaction between age and cognitive stimulation in the prediction of cognitive
      functioning. These conditions were investigated in a study in which 204 adults
      between 20 and 91 years of age completed an activity inventory and performed a
      variety of cognitive tasks. Only the 1st condition received empirical support,
      and, thus, the results of this study provide little evidence for the hypothesis
      that cognitive stimulation preserves or enhances cognitive functioning that would
      otherwise decline.

PMID- 12507354
TI  - Cognitive efficiency modes in old age: performance on sequential and coordinative
      verbal and visuospatial tasks.
AB  - In an experiment using a large set of verbal and spatial tasks requiring low or
      high degrees of executive control, 3 distinct age-related effects were found. The
      smallest effect (no slowing) was tied to lexical tasks with low executive
      involvement, the largest deficit (age-related slowing factor of 2.2) was tied to
      visuospatial tasks with high executive involvement, an intermediate level of
      deficit (slowing factor of 1.7) was found for visuospatial tasks with low
      executive load and verbal tasks with high executive load. These age-related
      dissociations were incompatible with any "common cause" formulation. The
      mechanism responsible for the dissociation between verbal and visual tasks, and
      between low and high executive load remains to be determined. The latter may
      reflect capacity limits.

PMID- 12507355
TI  - Affect optimization and affect complexity: modes and styles of regulation in
      adulthood.
AB  - In this research, the authors hypothesize that affect regulation involves 2
      independent strategies: affect optimization, the tendency to constrain affect to
      positive values, and affect complexity, the amplification of affect in the search
      for differentiation and objectivity. Community residents age 15 to 86 were
      assessed by using 2 convergent measurement domains: 1 based on measures of
      positive-negative affect and cognitive-affective complexity and 1 based on
      measures of coping and defense. Both domains yielded the hypothesized affect
      optimization and affect complexity dimensions. As predicted, the affect
      optimization dimensions are primarily related to relationship quality variables,
      and the affect complexity dimensions to socioeconomic status and education.
      Hence, positive affect and its maximization have different significance in the
      context of high- or low-affect complexity.

PMID- 12507356
TI  - Age-related equivalence and deficit in knowledge updating of cue effectiveness.
AB  - Knowledge updating involves learning about cue effectiveness based on task
      experience. Priorresearch has yielded inconsistent conclusions regarding age and
      knowledge updating. To resolve this inconsistency, the authors analyzed the
      effects of aging within a single paradigm. Participants studied cue-target
      associates during 2 study-test trials. Cues included rhyme cues and highly
      effective category cues. On each study-test trial, different items were
      presented, and participants predicted recall performance, received a cued recall
      test, and postdicted performance. Knowledge updating was operationalized as an
      improvement in the accuracy of predictive judgments across trials. An age deficit
      was evident in improvements in absolute accuracy, whereas age equivalence was
      evident in relative accuracy. Evidence suggested that deficient inferential
      processes contributed to the age deficit in knowledge updating.

PMID- 12507357
TI  - Age, executive function, and social decision making: a dorsolateral prefrontal
      theory of cognitive aging.
AB  - Current neuropsychological models propose that some age-related cognitive changes
      are due to frontal-lobe deterioration. However, these models have not considered
      the possible subdivision of the frontal lobes into the dorsolateral and
      ventromedial regions. This study assessed the age effects on 3 tasks of executive
      function and working memory, tasks dependent on dorsolateral prefrontal
      dysfunction; and 3 tasks of emotion and social decision making, tasks dependent
      on ventromedial prefrontal dysfunction. Age-related differences in performance
      were found on all tasks dependent on dorsolateral prefrontal dysfunction. In
      contrast, age-related differences were not found on the majority of the tasks
      dependent on ventromedial prefrontal dysfunction. The results support a specific
      dorsolateral prefrontal theory of cognitive changes with age, rather than a
      global decline in frontal-lobe function.

PMID- 12507358
TI  - Age and ethnicity differences in storytelling to young children: emotionality,
      relationality, and socialization.
AB  - Research has shown that age and ethnicity are associated with individuals'
      motivations for emotional regulation and social interaction. The authors proposed
      that these age and ethnicity-related motives would be reflected in storytelling.
      Women representing 2 age and 2 ethnic groups (young adulthood, oldage, African
      American, European American) told stories to young girls. Stories were coded for
      emotional, relational, and socialization focus. They predicted that older adults
      would selectively emphasize positive over negative emotions and would direct more
      utterances toward their interaction with their listener. The authors expected
      that African Americans would be more likely to emphasize socialization themes.
      Results suggest that older adults positively modulate emotional content while
      storytelling; qualified support was found for hypotheses concerning socialization
      and interrelational emphasis.

PMID- 12507359
TI  - Differential age effects for case and hue mixing in visual word recognition.
AB  - The authors compare older adults' lexical-decision data with younger adults' data
      reported in P. Allen, A. F. Smith, et al. (2002). On the basis of their work, it
      was proposed that consistent-case wordswould be processed by the faster holistic
      (magnodominated) stream, but that mixed-case words would be processed by the
      slower analytic (interblob-dominated or blob-dominated) steams. Hue mixing was
      predicted to have no effect on consistent-case performance, but mixed-hue/mixed
      case words were predicted to be recognized faster than monochrome/mixed-case
      words. Younger adults showed the predicted results, but older adults did not.
      These results suggest that holistic central processes are maintained, but that
      older adults exhibited an analytic decrement

PMID- 12507360
TI  - Emotionally charged autobiographical memories across the life span: the recall of
      happy, sad, traumatic, and involuntary memories.
AB  - A sample of 1,241 respondents between 20 and 93 years old were asked their age in
      their happiest, saddest, most traumatic, most important memory, and most recent
      involuntary memory. For older respondents, there was a clear bump in the 20s for
      the most important and happiest memories. In contrast, saddest and most traumatic
      memories showed a monotonically decreasing retention function. Happy involuntary
      memories were over twice as common as unhappy ones, and only happy involuntary
      memories showed a bump in the 20s. Life scripts favoring positive events in young
      adulthood can account for the findings. Standard accounts of the bump need to be
      modified, for example, by repression or reduced rehearsal of negative events due
      to life change or social censure.

PMID- 12507361
TI  - The effects of sad mood on memory in older adults: a test of the mood congruence
      effect.
AB  - Mood congruence effects have long been studied in younger adults, but not in
      older adults. Socioemotional selectivity theory (SST) suggests that mood
      congruence could operate differently in older adults. One hundred and nineteen
      younger and 78 older adults were randomly assigned to sad or neutral mood
      inductions, using combined Velten and music induction procedures. Results
      indicated that during sad mood induction both older and younger adults showed
      enhanced recall of sad words on delayed word list recall task and in
      autobiographical memory. However, only older adults displayed mood congruence
      effects on lexical ambiguity and lower recall of positive words in the word list
      task. Results provided partial support for developmental effects on mood
      congruence derived from SST.

PMID- 12507362
TI  - Asymmetric aging effects on semantic and phonological processes: naming in the
      picture-word interference task.
AB  - In 2 experiments, participants named pictures while ignoring auditory word
      distractors. For pictures with homophone names (e.g., ball), distractors
      semantically related to the nondepicted meaning (e.g., prom) facilitated naming
      by top-down phonological connections for young but not for older adults. Slowing
      from unrelated distractors and facilitation from phonologically related
      distractors were age invariant except in distractors that were both semantically
      and phonologically related. Only distractors semantically related to the picture
      interfered more for older than younger adults. These results ar einconsistent
      with age-linked deficits in inhibition of irrelevant information from either
      internal or external sources. Rather, aging affects priming transmission in a
      connectionist network with asymmetric effects on semantic and phonological
      connections involved in comprehension and production, respectively.

PMID- 12507363
TI  - Aging and autobiographical memory: dissociating episodic from semantic retrieval.
AB  - Cognitive aging research documents reduced access to contextually specific
      episodic details inolder adults, whereas access to semantic or other nonepisodic
      information is preserved or facilitated. The present study extended this finding
      to autobiographical memory by using a new measure; the Autobiographical
      Interview. Younger and older adults recalled events from 5 life periods.
      Protocols were scored according to a reliable system for categorizing episodic
      and nonepisodic information. Whereas younger adults were biased toward episodic
      details reflecting happenings, locations, perceptions, and thoughts, older adults
      favored semantic details not connected to a particular time and place. This
      pattern persisted after additional structured probing for contextual details. The
      Autobiographical Interview is a useful instrument for quantifying episodic and
      semantic contributions to personal remote memory.

PMID- 12507364
TI  - Can longitudinal changes in processing speed explain longitudinal age changes in
      fluid intelligence?
AB  - The processing-speed theory of cognitive aging contends tha age-related declines
      in intellectual function reflect the consequences of age-related slowing of
      processing speed. Cross-sectional data support this assumption. The association
      between 4-year changes in processing speed and 4-year changes in fluid
      intelligence was examined with a sample of 417 older adults. Changes in
      processing speed correlated .53 with changes in fluid intelligence. The
      difference in the explanatory power of processing speed regarding age-related
      differences and age-related changes is discussed with reference to other
      longitudinal studies and methodological considerations.

PMID- 12507365
TI  - Explorations in the social contagion of memory.
AB  - Four experiments examined social influence on the development of false memories.
      We employed the social contagion paradigm: A subject and a confederate see scenes
      and then later take turns recalling items from the scenes, with the confederate
      erroneously reporting some items that were not present in the scenes; on a final
      test, the subject reports these suggested items when instructed to recall only
      items from the scenes. The first two experiments showed that the social contagion
      effect persisted when subjects were explicitly warned about the possibility that
      confederates' responses might induce false memories and when they were tested via
      source-monitoring tests that explicitly gave the choice of attributing suggested
      items to the other person. Levels of false recall and recognition increased with
      the number of times the misleading information was suggested (Experiment 3), and
      subjects were more likely to incorporate the erroneous responses of an actual
      confederate on a recognition/source test as compared with those of a simulated
      confederate (Experiment 4). Collectively, the data support the claim that false
      memories may be transmitted between people and reveal critical factors that
      modulate the social contagion of memories.

PMID- 12507366
TI  - Tunnel memories for autobiographical events: central details are remembered more
      frequently from shocking than from happy experiences.
AB  - In three experiments, undergraduates recorded as many details as possible for
      autobiographical memories of highly positive and highly negative events in their
      lives. Experiment 1 replicated earlier findings for memories of highly negative
      events: Central details were recorded more frequently than peripheral details,
      and a weak correlation was found between emotional intensity and number of
      central details. In Experiment 2, undergraduates recorded details of memories of
      both their happiest and their most shocking events. Central details dominated
      over peripheral details only in memories of shocking events. This finding was
      replicated in Experiment 3. Recording memory details affected the participants'
      moods and generated a mood congruence effect in a subsequent recall of word-cued
      memories. The finding suggest that tunnel memories--enhanced memory for the
      central details of an event--are limited to emotionally negative memories. The
      findings contradict expectations derived from the notion of repression.

PMID- 12507367
TI  - Conceptual and perceptual processes in prospective remembering: differential
      influence of attentional resources.
AB  - Does prospective remembering rely on strategic, attentionally demanding
      processes? We report three experiments suggesting that the extent to which
      attentional processes are required varies according to the character of ongoing
      task processing. Study-test changes in the semantic context of targets had a
      negative effect on prospective memory performance when participants were engaged
      in a conceptually focused (sentence verification) task (Experiment 1). Similarly,
      prospective remembering was lower following study-test changes in perceptual
      format (font) in the context of a perceptually focused (readability rating)
      ongoing task (Experiment 2). However, although dividing attention at retrieval
      had a negative effect during the performance of an ongoing conceptual task
      (Experiments 1 and 3), it had no effect during an ongoing perceptual task
      (Experiments 2 and 3). Thus, both perceptual and conceptual process are
      implicated in prospective remembering, but the processing focus of the task in
      which remembering should occur may mediate the requirement for strategic
      processes. These findings suggest that more than one retrieval route is available
      for prospective remembering and that selection of the route depends on the nature
      of the task and the processing that occurs at encoding and retrieval.

PMID- 12507368
TI  - Perceptual and conceptual priming in patients with dissociative identity
      disorder.
AB  - The present study examined implicit memory transfer in patients with dissociative
      identity disorder (DID). To determine priming impairments in DID, we included
      both several perceptual priming tasks and a conceptual priming task using neutral
      material. We tested a large sample of DID patients (n = 31), in addition to 25
      controls and 25 DID simulators, comparable on sex, age, and education. Controls
      replicated conceptual priming results of Vriezen, Moscovitch, and Bellos (1995)
      by showing that conceptual priming seems to require the formation of domain
      specific semantic representations, denoting either sensory or functional object
      attributes. We extended a study performed by Schacter, Cooper, and Delaney (1990)
      by demonstrating priming for impossible object using the sensitive priming index
      of response times. The simulators in the study were not able to simulate
      interidentity amnesia on the implicit memory tasks employed. Partly in contrast
      to participants in previous studies, DID patients showed evidence of perceptual
      priming as well as conceptual priming comparable to that of controls. DID
      patients thus displayed normal implicit memory performance.

PMID- 12507369
TI  - Positive and negative generation effects, hypermnesia, and total recall time.
AB  - Self-generated information is typically remembered better than perceived
      information (the generation effect). Experimental design produces an important
      limiting condition for this effect: Generation enhances recall in within-subjects
      designs, but typically not in between-subjects designs. However, Mulligan (2001)
      found that the generation effect emerged over repeated recall tests in a between
      subjects design, calling into question the generality of this limiting condition.
      Two experiments further delineated the emergent generation effect Experiment 1
      demonstrated that this effect does not require multiple discrete recall tests but
      may emerge on a single recall test of long duration. Experiment 2 demonstrated
      that the negative generation effect (a reversal of the typical generation effect
      produced under certain conditions) is abolished by multiple recall tests. In both
      experiments, the generate condition produced greater hypemnesia (increased recall
      over tests) than did the read condition.

PMID- 12507370
TI  - Are false memories more difficult to forget than accurate memories? The effect of
      retention interval on recall and recognition.
AB  - What is the effect of retention interval on accurate and false recollection in
      the Deese, Roediger, and McDermott (DRM) procedure? Previous research has
      suggested that false recall is more persistent than accurate recall but the
      recognition results have been inconsistent. In two parametric studies, we tested
      recall and recognition for the same DRM lists, over retention intervals that
      ranged from no delay to a 2-month delay. We found that accurate and false memory
      were diminished by increases in retention interval, false memory persistence was
      present for recall and recognition, greater persistence for false memory than for
      accurate memory was more readily observed for recall than recognition, and the
      high-threshold (Pr), signal detection (d'), and nonparametric (A') recognition
      measures differed in their sensitivity for detecting change. The effect of
      retention interval on accurate and false memory is consistent with expectations
      from fuzzy trace theory. In the DRM procedure, truth is not more memorable than
      fiction.

PMID- 12507371
TI  - The effect of warnings on false memories in young and older adults.
AB  - In the present experiments, we examined adult age differences in the ability to
      suppress false memories, using the Deese-Roediger-McDermott (DRM) paradigm
      (Deese, 1959; Roediger & McDermott, 1995). Participants studied lists of words
      (e.g., bed, rest, awake, etc.), each related to a nonpresented critical lure word
      (e.g., sleep). Typically, recognition tests reveal false alarms to critical lures
      at rates comparable to those for hits for studied words. In two experiments,
      separate groups of young and older adults were unwarned about the false memory
      effect, warned before studying the lists, or warned after study and before test.
      Lists were presented at either a slow rate (4 sec/word) or a faster rate (2
      sec/word). Young adults were better able to discriminate between studied words
      and critical lures when warned about the DRM effect either before study or after
      study but before retrieval, and their performance improved with a slower
      presentation rate. Older adults were able to discriminate between studied words
      and critical lures when given warnings before study, but not when given warnings
      after study but before retrieval. Performance on a working memory capacity
      measure predicted false recognition following study and retrieval warnings. The
      results suggest that effective use of warnings to reduce false memories is
      contingent on the quality and type of encoded information, as well as on whether
      that information is accessed at retrieval. Furthermore, discriminating between
      similar sources of activation is dependent on working memory capacity, which
      declines with advancing age.

PMID- 12507372
TI  - The effects of aging on selectivity and control in short-term recall.
AB  - The ability to control encoding and retrieval processing strategically is
      critical for the efficient use of memory. We examined the ability of younger and
      older adults to selectively remember words on the basis of their arbitrary point
      values by using a technique developed by Watkins and Bloom (1999). In the first
      three experiments, younger subjects recalled more words than did older subjects,
      but an independent index of recall selectivity showed that older subjects were
      apparently more successful in selecting higher valued words. However, a fourth
      experiment showed that this superior selectivity on the part of older adults was
      attributable to their greater proportional reliance on primary memory recall.
      Overall, the data suggest that although older adults recall fewer words than do
      younger adults, they exert as much control over some aspects of encoding.

PMID- 12507373
TI  - Concurrent performance of two memory tasks: evidence for domain-specific working
      memory systems.
AB  - Previous studies of dual-task coordination in working memory have shown a lack of
      dual-task interference when a verbal memory task is combined with concurrent
      perceptuomotor tracking. Two experiments are reported in which participants were
      required to perform pairwise combinations of (1) a verbal memory task, a visual
      memory task, and perceptuomotor tracking (Experiment 1), and (2) pairwise
      combinations of the two memory tasks and articulatory suppression (Experiment 2).
      Tracking resulted in no disruption of the verbal memory preload over and above
      the impact of a delay in recall and showed only minimal disruption of the
      retention of the visual memory load. Performing an ongoing verbal memory task had
      virtually no impact on retention of a visual memory preload or vice versa,
      indicating that performing two demanding memory tasks results in little mutual
      interference. Experiment 2 also showed minimal disruption when the two memory
      tasks were combined, although verbal memory (but not visual memory) was clearly
      disrupted by articulatory suppression interpolated between presentation and
      recall. These data suggest that a multiple-component working memory model
      provides a better account for performance in concurrent immediate memory tasks
      than do theories that assume a single processing and storage system or a limited
      capacity attentional system coupled with activated memory traces.

PMID- 12507374
TI  - Presentation format and its effect on working memory.
AB  - In three experiments, we examined the separate cognitive demands of processing
      and storage in working memory and looked at how effective the coordination was
      when items for storage varied in format/modality. A sentence verification task
      involving arithmetic facts was combined with a span task involving two to six
      items presented in picture, printed word, or spoken word format. The first two
      experiments were the same, except for the added requirement of articulation of
      the math sentence in Experiment 2. Experiment 3 varied the length of the span
      item and compared recall with recognition performance. The results showed that
      both spoken words and picture produced superior recall and recognition, as
      compared with printed words, and are consistent with Baddeley and Logie's (1999)
      and Mayer's (2001) models of working memory. Also, the differences in processing
      performance across spans varied with the difficulty of the task but showed the
      strongest support for the resource allocation model (Foos 1995).

PMID- 12507375
TI  - Cascaded versus noncascaded models of lexical and semantic processing: the turple
      effect.
AB  - The density of the orthographic neighborhood surrounding an item has been shown
      to have an inhibitory effect for nonwords in a lexical decision experiment. Four
      experiments are reported investigating whether a similar pattern holds for a
      semantic categorization task (animal vs. non-animal). In the first experiment, no
      effects of neighborhood density were found for nonexemplars, whether they were
      words or nonwords. The absence of any inhibitory effect for nonwords implies that
      close orthographic neighbors are ignored. However, the second experiment showed
      that if the nonword has a neighbor that is an animal name (eg., turple), an
      interference effect is observed, implying that neighbors do exert an effect if
      they have the right semantic properties. The same items showed no additional
      interference in lexical decision. These results suggest the involvement of
      semantic properties very early in the processing cycle. A cascaded processing
      system monitoring activation in semantic features can explain these results, but
      cannot explain the frequency effect observed for nonexemplar words or the fact
      that variation in density is irrelevant when one of the neighbors is an exemplar.
      It is argued that existing models of semantic categorization must be extended to
      accommodate these results.

PMID- 12507376
TI  - Priming in deduction: a spatial arrangement task.
AB  - The mental model theory assumes that people reason by manipulating mental
      representations of states of the word, called "mental models." In the present
      study we used a new deduction task based on diagrammatic premises. We show that a
      premise can prime other premises that induce similar mental models in a way
      analogous to the case of words with related meanings, which prime one another. We
      present three experiments. In Experiment 1 we used an evaluation task. In
      Experiment 2, a construction task was used. The priming effect was obtained in
      both cases. In a third experiment we show that the priming effect was still
      present when partcipants were instructed to ignore a prime displayed before the
      premises. In all three experiments we compared determinate and indeterminate
      problems and found faster responses in the former.

PMID- 12507377
TI  - How temporal assumptions influence causal judgments.
AB  - Causal learning typically entails the problem of being confronted with a large
      number of potentially relevant statistical relations. One type of constraint that
      may guide the choice of appropriate statistical indicators of causality are
      assumptions about temporal delays between causes and effects. There have been a
      few previous studies in which the role of temporal relations in the learning of
      events that are experienced in real time have been investigated. However, human
      causal reasoning may also be based on verbally described events, rather than on
      direct experiences of the events to which the descriptions refer. The aim of this
      paper is to investigate whether assumptions about the temporal characteristics of
      the events that are being described also affect causal judgment. Three
      experiments are presented that demonstrate that different temporal assumptions
      about causal delays may lead to dramatically different causal judgments, despite
      identical leaning inputs. In particular, the experiments show that temporal
      assumptions guide the choice of appropriate statistical indicators of causality
      by structuring the event stream (Experiment 1), by selecting the potential causes
      among a set of competing candidates (Experiment 2), and by influencing the level
      of aggregation of events (Experiment 3).

PMID- 12507378
TI  - Momentary and integrative response strategies in causal judgment.
AB  - Associative models of causal learning predict recency effects. Judgments at the
      end of a trial series should be strongly biased by recently presented
      information. Prior research, however, presents a contrasting picture of human
      performance. Lopez, Shanks, Almaraz, and Fernandez (1998) observed recency,
      whereas Dennis and Ahn (2001) found the opposite, primacy. Here we replicate both
      of these effects and provide an explanation for this paradox. Four experiments
      show that the effect of trial order on judgments is a function of judgment
      frequency, where incremental judgments lead to recency while single final
      judgments abolish recency and lead instead to integration of information across
      trials (i.e., primacy). These results challenge almost all existing accounts of
      causal judgment. We propose a modified associative account in which participants
      can base their causal judgments either on current associative strength (momentary
      strategy) or on the cumulative change in associative strength since the previous
      judgment (integrative strategy).

PMID- 12507379
TI  - Alignment effects on learning multiple, use-relevant classification systems.
AB  - People often learn multiple classification systems that are relevant to some goal
      or use. We compared conditions in which subclassification within a category
      hierarchy was predicted by values on either the same (alignable) or different
      (nonalignable) dimensions between category hierarchies. The results indicated
      that learning in alignable conditions occurred in fewer blocks and with fewer
      errors than did learning in nonalignable conditions. This facilitation was not
      the result of differences between conditions in the representations learned by
      the participants, the number of dimensions needed for subclassification
      (Experiment 1), or the objective complexity of the learning task (Experiment 2).
      The facilitated learning in the alignable conditions appears to reflect a
      commitment on the part of the learner to alignment: the belief that the structure
      relevant to the use of one category system will also be relevant to the use of a
      comparable system.

PMID- 12507380
TI  - Decomposing the problem-size effect: a comparison of response time distributions
      across cultures.
AB  - Is the locus of the problem-size effect in mental arithmetic different across
      cultures? In a novel approach to this question, the ex-Gaussian distributional
      model was applied to response times for large (e.g., 8 x 9) and small (e.g., 2 x
      3) problems obtained from Chinese and Canadian graduate students in a
      multiplication production task (LeFevre & Liu, 1997). The problem-size effect for
      the Chinese group occurred in mu (the mean of the normal component), whereas the
      problem-size effect for the Canadian group occurred in both mu and tau (the mean
      of the exponential component). The results support the position that the problem
      size effect for the Chinese group is purely a memory-retrieval effect, whereas
      for the Canadian group, it is an effect of both retrieval and the use of
      nonretrieval solution procedures.

PMID- 12507381
TI  - Morphologic variations in bacteria under stress conditions: near-field optical
      studies.
AB  - The morphologic and structural variations suffered by cells of a population of
      Pseudomonas aeruginosa ATCC 27853 under stress conditions were investigated by
      using scanning near-field optical microscopy. The analysis of the images,
      supported by microbiological data, showed that the bacteria evolved from the
      initial distribution of rod-shaped cells of standard size to a population with
      structural and morphologic modifications. The detection of variations in the
      optical reflectivity over a subwavelength scale (< or = 100 nm), combined with
      the concurrently acquired topographical signal, allowed the visualisation of rod
      shaped bacteria going towards a lytic process and entire "U"-shaped cells. In the
      latter cells, which derived from a morphology refolding of rod bacteria, cellular
      matter seemed to rearrange itself to attain a coccoid stress resistant form,
      responsible for the residual viability of the population.

PMID- 12507382
TI  - The two-dimensional and three-dimensional processing of images provided by
      conventional microscopes.
AB  - In this paper, I present an interesting processing method of microscopic images.
      High-pass type filters are generally used for image focusing. They enhance the
      high spatial frequencies. They are, however, efficient only in cases when the
      picture is not sharp because of the low contrast on high frequencies (for example
      in a TV picture). These filters, are not appropriate if the lack of sharpness has
      been caused by other factors. In this case, it is not possible to construct a
      three-dimensional model of the observed object. Better results and a three
      dimensional model can be obtained by applying the following theory. As part of
      this paper, an original program based on this theory is described.

PMID- 12507383
TI  - Characterization of atmospheric particles by electron probe X-ray microanalysis.
AB  - Microchemical glass standards were used to validate a quantitation method based
      on peak-to-background (P/B) ratios from electron probe x-ray microanalysis
      spectra. This standardless method was applied to the determination of
      concentrations of individual particles from Malpha or Lalpha lines, as well as
      from Kalpha lines. The algorithm was tested on particulate glass samples for
      diameters ranging from 1 to 20 microm. The determined concentrations did not
      depend on particle size. The certified values for elements were well matched,
      except for Na, which may migrate under electron bombardment. Finally,
      classification of qualitative results obtained for aerosol particles was
      completed by the P/B quantitative method.

PMID- 12507384
TI  - Confocal endoscopy via structured illumination.
AB  - We describe a simple modification to a rigid endoscope so as to provide both high
      quality conventional and confocal images of reasonably accessible regions of the
      body. This versatile system uses a structured illumination approach together with
      a conventional incoherent illumination source. Images taken in fluorescence are
      presented using this combined conventional and confocal endoscope.

PMID- 12507385
TI  - Optimisation of the environmental scanning electron microscope for observation of
      drying of matt water-based lacquers.
AB  - Environmental scanning electron microscopy (ESEM) modifies conventional SEM
      through the use of a partial gas pressure in the microscope specimen chamber.
      Like conventional SEM, it has the resolution to image structure on the submicron
      lengthscale, but can also tolerate hydrated specimens if water vapour is used in
      the specimen chamber. This ability to image aqueous specimens leaves ESEM
      uniquely placed to study in situ drying in polymer latexes. However, there are
      two key practical difficulties associated with in situ drying. First, the size of
      the latex particles: larger latex particles are typically around 500 nm in
      diameter. Although ESEM can resolve structure on this lengthscale without
      difficulty, the magnification required results in radiation damage of the
      specimen due to the electron beam. This means that a given region can be imaged
      only once during film formation, so the evolution of particular features cannot
      be followed. Second, the change from ambient temperature and pressure to the ESEM
      conditions of 7 degrees C and 7.5 torr (100 Pa) can subject the specimen to a
      very high evaporation rate, which can disrupt film formation. The inclusion of a
      drop of water in the specimen chamber is shown largely to alleviate this,
      enabling successful imaging of film formation in the lacquer. Instead of the
      polymer latex itself, this work concentrates on a matting lacquer with silica
      inclusions. The silica matting agent particles are 1-10 microm in size, allowing
      for a lower magnification to be used, massively reducing specimen damage.
      Furthermore, the contrast during drying is much enhanced in the presence of
      silica. The images reveal the silica as bright regions against a darker
      background of polymer and water. Film formation shows the transition from a
      uniform, featureless aqueous solution to a polymer film with silica particles
      present on the surface. The appearance of individual silica particles can be
      followed. The particles are generally revealed quite early, after a few minutes
      of drying time. As film formation progresses, these same particles appear larger
      and more distinct. Few new particles are revealed at longer film formation times.

PMID- 12507386
TI  - Cytochrome oxidase activity and confocal laser scanning microscopic analysis of
      the hamster submandibular gland using microwave irradiated fixation.
AB  - Submandibular glands of the hamster were irradiated in 2% paraformaldehyde (pFA)
      0.5% pure glutaraldehyde (PGA) with a microwave (MW) processor at temperatures of
      10 degrees and 37 degrees C. Electron microscopy showed that cytochrome oxidase
      activity was taking place in the mitochondrial intermembrane-intracristal space
      of the granular duct cell when the temperature of the MW-irradiated fixatives was
      at 10 degrees C. However, a decrease of this activity was observed when we took
      care to keep the temperature of the MW-irradiated fixatives at 37 degrees C. The
      distinct reduction of cytochrome oxidase activity allowed by MW irradiation seems
      to be due the thermal affects of fixatives. Of course, the possibility cannot be
      excluded that MW irradiation caused other undetectable membrane damage. Then, we
      used confocal laser scanning microscopy for the preservation check of the
      mitochondrial membrane for cytochemistry with MW-irradiated fixation. The
      fluorescence of rhodamine 123 was observed in the inner spaces of the
      mitochondria at temperatures of 10 degrees and 37 degrees C. When the same
      tissues were fixed with 2% pFA using an MW processor as the sole fixative at 10
      degrees C, no mitochondrial fluorescence was observed. Cytochrome oxidase
      activity, by contrast, could be seen in the mitochondrial intermembrane
      intracristal spaces in the same condition. Formaldehyde is not the best aldehyde
      for the purpose of ultrastructural preservation. On the other hand, light and
      electron microscopy showed that the endogenous peroxidase activity was localized
      in the nuclear envelope, endoplasmic reticulum, secretory granules, and Golgi
      apparatus of the hamster submandibular gland using 2% pFA-0.5% PGA fixative with
      and without MW irradiations at temperatures of 10 degrees and 37 degrees C. Some
      of the same cells were fixed with only 2% pFA under MW irradiation at 10 degrees
      C; however, marked diffuseness of the peroxidase activity was observed.
      Therefore, these results indicated that cytochrome oxidase activity was sensitive
      to heat with MW-irradiated fixation. Peroxidase activity was very resistant to
      heat with MW-irradiated fixation but not with pFA solo fixation, therefore, PGA
      had to be used.

PMID- 12507387
TI  - The porosome--a new cellular structure.

PMID- 12507388
TI  - Temperature dependence of synaptic responses in guinea pig hippocampal CA1
      neurons in vitro.
AB  - 1. Temperature-dependent properties of synaptic transmission were studied by
      recording orthodromic responses of the population spike and excitatory
      postsynaptic potential in CA1 pyramidal neurons of guinea pig hippocampal slices.
      2. Increasing the temperature of the perfusing medium from 30 to 43 degrees C
      resulted in a decrease in the amplitude of the population spike (A-PS) and a
      reduced slope of the excitatory postsynaptic potential (S-EPSP). Bath application
      of the gamma-aminobutyric acid receptor antagonist, picrotoxin, or a change in
      the calcium concentration of the perfusate did not affect the A-PS during
      heating. 3. Increasing the strength of the synaptic input to that eliciting a PS
      with an amplitude 50, 75, or 100% of maximal at 30 degrees C resulted in a
      significant increase in the A-PS during the middle phase of hyperthermia (35-39
      degrees C). 4. The long-term potentiation (LTP) induced at either 30 or 37
      degrees C showed the same percentage increase in both the amplitude of the
      population spike and the S-EPSP after delivery of a tetanus (100 Hz. 100 pulses)
      to CA1 synapses. 5. The results of the present study, therefore, indicate that
      the decrease in CA1 field potential was linearly related to the temperature of
      the slice preparation, while LTP was induced in these responses during heating
      from 30 to 37 degrees C.

PMID- 12507389
TI  - Possible involvement of Fas system in the induction of apoptosis in human
      astrocytic brain tumors.
AB  - 1. For a better understanding of the biological features of astrocytic tumors, we
      investigated apoptosis and its pathway, especially in the interaction between Fas
      and Fas ligand (FasL). 2. We examined the presence of apoptosis in human
      astrocytic brain tumors by terminal deoxynucleotidyl transferase (TdT)-mediated d
      UTP-biotin nick end labeling (TUNEL) and then apoptotic index (AI) was
      calculated. We also examined the distribution of Fas and FasL-positive tumor
      cells immunohistochemically. Labeling index (LI) for Fas and FasL was calculated
      as Fas-LI and FasL-LI, respectively, and compared to AI. 3. Tumor cells
      expressing both Fas and FasL were TUNEL positive. Such cells were distributed
      sparsely in low-grade astrocytomas, but focally in glioblastomas. There was a
      close correlation among AI, Fas-LI, and FasL-LI, and astrocytic tumors with
      higher Al were associated with a longer survival time than that with lower Al. 4.
      It was concluded that the Fas system may be involved in the apoptosis of
      astrocytic tumors, and Al can be a useful parameter for assessing prognosis of
      astrocytic tumors.

PMID- 12507390
TI  - Microarray analysis of neural stem cell differentiation in the striatum of the
      fetal rat.
AB  - 1. Gene expression profiles in neural stem cell differentiation in vitro were
      determined by cDNA microarray analysis. 2. Total RNA was extracted and reverse
      transcripted into cDNA from differentiated and undifferentiated neural stem
      cells. The 33P labeled cDNA was hybridized with a cDNA microarray consisting of
      14,000 human genes. 3. The results showed that a total of 1406 genes were
      differentially expressed, of which 148 genes exhibited more than twofold
      differences. Some genes were obviously activated while others were strongly
      repressed. These changes in gene expression suggest that differentiation is
      regulated by different genes at different expressional levels. By biological
      classification, the differentially expressed genes were divided into four
      functional categories: molecular function, biological process, cellular
      component, and new functional genes or ESTs. 4. These findings will be a valuable
      contribution for gene expression profiling and elucidation of neural stem cell
      differentiation mechanisms.

PMID- 12507391
TI  - Evidence for implication of tryptophan hydroxylase in the regulation of melatonin
      synthesis in ovine pinealocytes in culture.
AB  - 1. Tryptophan hydroxylase (TPOH) is the first enzyme in the melatonin synthesis
      pathway and the rate-limiting enzyme in serotonin synthesis. We established in
      this study an in vitro model of ovine pinealocytes to investigate the role of
      TPOH in melatonin production. 2. We demonstrated that TPOH is highly expressed
      both in vivo and in vitro at the protein and mRNA levels. In vitro pinealocytes
      show ultrastructural features similar to those previously described in vivo. 3.
      Moreover, our in vitro model allowed us to study the regulation mechanisms for
      melatonin synthesis in sheep pinealocytes and to demonstrate that both
      transcriptional and posttranscriptional mechanisms are involved. 4. In
      particular, our results suggest that TPOH plays an essential role in the
      regulation of melatonin synthesis.

PMID- 12507392
TI  - Dexamethasone attenuates by colchicine induced Fos expression in the rat deep
      cerebellar and vestibular nuclei.
AB  - 1. The intent of the present study was to find out whether dexamethasone
      pretreatment may affect the induction of Fos protein in cell nuclei of the
      cerebellar vestibular neuronal complex (CVNC) elicited by central administration
      of colchicine. Specifically, the rate of the dexamethasone-sensitive cell
      population was analyzed and compared at different levels of the CVNC using a
      light microscopic avidin-biotin peroxidase immunohistochemistry. 2. Male Wistar
      rats were pretreated with dexamethasone 3 days prior (2.5 mg/kg/day, s.c.) and 24
      h after an intracerebroventricular delivery of colchicine (60 microg/10 microL).
      Animals were sacrificed 48 h after colchicine treatment by a transcardial
      perfusion with fixative. 3. Dexamethasone in itself had no effect on the activity
      of cells of the CVNC. However, in colchicine treated animals, which exhibited a
      large number of Fos-positive cells over the entire CVNC, the dexamethasone
      elicited a substantial reduction in the number of the Fos-immunoreactive cells
      over the CVNC. Distinct dexamethasone dependent reduction (50-90%) of Fos
      immunoreactivity was observed in each of the deep cerebellar nuclei. On the other
      hand, less number of dexamethasone-sensitive cells were recognized in the
      vestibular structures. From these, maximal Fos-inhibition by dexamethasone was
      recognized in the medial vestibular nucleus, however, even in this case the
      number of suppressed cells did not exceed 50%. 4. The results provide for the
      first time evidence about the dexamethasone dependent reduction of Fos
      immunoreactivity in the cells of the CVNC in response to stimulation elicited by
      colchicine. The data also indicate that the glucocorticoids might be involved in
      the regulation of some functions of the CVNC under stress conditions.

PMID- 12507393
TI  - Allopregnanolone increase in striatal N-methyl-D-aspartic acid evoked
      [3H]dopamine release is estrogen and progesterone dependent.
AB  - 1. The neurosteroids are compounds derived from steroid hormones and synthesized
      in the nervous system. They can modulate different neurotransmitter pathways. In
      previous work we demonstrated that progesterone modulates dopamine release
      induced by the glutamatergic agonist N-methyl-D-aspartic acid (NMDA). 2. The aim
      of this work was to evaluate a possible modulatory role of the progesterone
      metabolite allopregnanolone on NMDA-evoked [3H]dopamine release from corpus
      striatum slices obtained from cycling and ovariectomized female rats. 3. We used
      a dynamic superfusion method to evaluate the release of [3H]dopamine.
      Allopregnanolone at 50-600 nM was added to the superfusion buffer (Krebs-Ringer
      bicarbonate-glucose. pH 7.4. with constant O2/CO2 gassing). The results are
      expressed as a percentage over basal [3H]dopamine loaded by the tissue. 4.
      Allopregnanolone (50 and 100 nM) increased the NMDA-evoked [3H]dopamine release
      from estrus rats. The remaining doses did not show significant changes in the
      pattern of release. This effect was not observed in diestrus rats. The
      ovariectomy abolished the facilitatory effect of allopregnanolone on NMDA-evoked
      2 [3H]dopamine release. 5. Subcutaneous administration of exogenous estrogen (25
      mg/rat) and progesterone (1 mg/rat) restored the facilitatory effect on
      dopaminergic input. 6. These results suggest that allopregnanolone is a
      neurosteroid able to modulate dopamine release in an ovarian-hormone-fluctuation
      dependent manner and provide further support for a role of allopregnanolone as a
      modulator of glutamatergic-dopaminergic interaction in the corpus striatum.

PMID- 12507394
TI  - Transient forebrain ischemia increases the blood-brain barrier permeability for
      albumin in stroke-prone spontaneously hypertensive rats.
AB  - 1. The aim of the present study was to reveal the effect of transient forebrain
      ischemia on the regional and temporal changes in the permeability of the blood
      brain barrier (BBB) permeability for sodium fluorescein (MW: 376 Da) and Evan's
      blue-labeled albumin (MW: 67 kDa) in stroke-prone spontaneously hypertensive rats
      (SHRSP). 2. BBB permeability was significantly higher in the brain regions of 16
      week-old control SHRSP than those in age-matched normotensive Wistar-Kyoto rats.
      3. Transient forebrain ischemia evoked by 10-min bilateral carotid occlusion
      increased the permeability of the BBB for albumin, but not for sodium
      fluorescein, after 6 and 24 h of reperfusion in brain regions of SHRSP. 4.
      Extravasation of serum macromolecules may contribute to neuronal loss and
      development of hypertensive encephalopathy in SHRSP.

PMID- 12507395
TI  - Time course of upregulation of fibrogenic growth factors and cellular
      infiltration in a rodent model of chronic renal allograft rejection.
AB  - BACKGROUND: Chronic Rejection (CR) is the leading cause of renal allograft
      dysfunction. Upregulation of growth factors has been shown in CR but the time
      point at which this occurs in not known. The aim of this study was to examine the
      time course of upregulation of growth factors and correlate this with the
      macrophage and myofibroblast interstitial infiltrate. METHODS: Using a rat model
      of CR (F344 kidney donor to Lewis recipient), infiltration by ED1 + macrophages
      and proliferation of alpha-smooth muscle actin (alpha-SMA) and desmin-expressing
      cells was examined using immunohistochemistry. In addition, expression of mRNA
      for interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta),
      basic-fibroblast growth factor (b-FGF) and vascular endothelial growth factor
      (VEGF) was studied using a semi-quantitative reverse transcriptase polymerase
      chain reaction (RT-PCR) technique. Native Lewis rat kidney and Lewis-Lewis
      isografts were used as controls. RESULTS: Immunohistochemical staining of ED1 +
      cells showed a marked increase in the macrophage infiltrate of allografts
      compared to isografts at all time periods (P = 0.0002) peaking at weeks 8-12
      after transplantation. Expression of alpha-SMA was also increased in allografts
      (P = 0.002). RT-PCR analysis showed that mRNA for TGF-beta was maximally
      upregulated in allografts in comparison to isografts at week 8 after engraftment
      (P = 0.05) and declined thereafter, although remained at elevated levels compared
      to controls. IFN-gamma and b-FGF gene expression was increased in allografts late
      in the post-transplantation period. CONCLUSION: Early infiltration of macrophages
      and production of TGF-beta1 was followed by later upregulation of fibrogenic
      growth factors and myofibroblasts associated with interstitial fibrosis and organ
      dysfunction.

PMID- 12507396
TI  - The effects of cyclosporine on antioxidant enzyme activities and malondialdehyde
      levels in rabbit hepatic tissues.
AB  - Possible molecular mechanisms leading to cyclosporine-induced hepatotoxicity has
      not been cleared yet. Therefore, investigation of antioxidant status of hepatic
      tissues exposed to cyclosporine A (CsA) and of free radical involvement in the
      CsA-induced hepatotoxicity seems of importance. For this aim, 20 rabbits were
      used in the study. In each group (control, CsA, CsA plus vitamin and, vitamin
      only) there were 5 animals. CsA was given orally (25 mg/kg/day) for 10 days.
      Vitamins E (100 mg/kg/ day) and C (200 mg/kg/day) combination was injected
      intramuscularly. After 10th day, animals were killed, and livers were prepared
      for the enzymatic assays. Activities of superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT) and, malondialdehyde (MDA) levels were
      determined in the supernatant fractions. Lowered SOD, unchanged GSH-Px and,
      increased CAT activities and MDA levels were detected in hepatic tissues of
      rabbits treated with CsA as compared with controls. In the CsA plus vitamin
      group, SOD activity was found to be higher, GSH-Px and CAT activities unchanged
      and MDA levels lower than the CsA group. In the vitamin-treated group, all of the
      enzyme activities were higher than the controls but MDA levels were unchanged.
      Correlation analysis revealed some significant differences between the groups.
      Results suggest that cyclosporine impairs the antioxidant defense system and
      thus, leads to oxidant stress and peroxidation in rabbit hepatic tissues. It has
      been established that this process can be prevented by antioxidant vitamin
      supplementation.

PMID- 12507397
TI  - LSF-1 may modulate the indirect allorecognition pathway to delay allograft
      rejection.
AB  - Liver suppressor factor one (LSF-1) is a 40-kDa immunosuppressive protein in the
      serum of rats 60 days after orthotopic liver transplantation (OLT) between the
      non-rejector combination of DA donors into PVG recipients. In the present study,
      a polyclonal anti-LSF-1 antibody was used to detect the lymphoid cell populations
      expressing LSF-1 epitopes in several transplant models. In this study we examined
      cell samples acquired from rats that had undergone OLT in syngeneic, rejecting or
      non-rejecting combinations. Flow cytometry indicated that the polyclonal antibody
      reacts specifically with an epitope present on a CD4 CD11b positive cell of
      recipient origin. In the first 3 weeks after transplant there is a large increase
      in the number of these cells isolated from the spleens and livers of rats in
      tolerogenic OLT model, which correlates with prolongation of allograft survival.
      In the rejector and isograft models of OLT there is a minimal change in the
      expression of the LSF-1 N-terminal pep epitope. These results suggest that these
      recipient CD4 CD11b cells may have a critical role in the formation of transplant
      tolerance by interfering with the indirect pathway of allorecognition via as yet
      undetermined mechanisms. The increased expression of the LSF-1 N-terminal pep
      epitope on liver leukocytes 14 days after partial hepatectomy indicates a natural
      role for LSF-1 in the process of liver regeneration after insult or injury.

PMID- 12507398
TI  - Enhanced apoptosis of peripheral blood mononuclear cells in cardiac transplanted
      patients undergoing chronic immunosuppressive treatment.
AB  - Apoptosis plays a major role in tissue transplantation because intact T-cell
      apoptosis pathways are required for the induction of tolerance to allografts.
      Moreover, immunosuppressive agents commonly used in clinical transplantation
      medicine promote lymphocyte apoptosis inhibiting the expression and production of
      cytokines involved in lymphocyte survival. The aim of our study was to evaluate
      peripheral blood mononuclear cells (PBMC) spontaneous apoptosis in patients
      undergoing chronic immunosuppressive treatment after cardiac transplantation.
      PBMC obtained from patients (n = 31) and controls matched for age and sex (n =
      25) were cultured for 72 h and apoptosis was evaluated by quantification of
      fragmented DNA, staining with Hoechst 33258 dye and annexin V binding. We also
      investigated Fas expression and FasL mRNA expression as well as the ability of an
      IgM anti-Fas antibody to induce apoptosis. Finally, we evaluated IL2 production
      induced by PHA and the ability of IL2 to prevent apoptosis. In patients, PBMC
      underwent enhanced spontaneous apoptosis in comparison with controls. However, we
      could not find any difference between patients and normals as regards the
      expression of Fas and of FasL mRNA, even if the cross-linking of the Fas molecule
      induced apoptosis in PBMC from patients, whereas it failed to induce cell death
      in normals. We also found that IL2 production was significantly decreased in
      patients and that the addition of IL2 to the culture medium reduced PBMC
      spontaneous apoptosis. Our findings suggest that in cardiac transplanted patients
      PBMC undergo enhanced spontaneous apoptosis, which may contribute to prevent
      allograft rejection.

PMID- 12507399
TI  - The role of nitric oxide pathway in the renal ischemia-reperfusion injury in
      rats.
AB  - INTRODUCTION: Nitric oxide (NO), synthesized from L-arginine by the enzyme nitric
      oxide synthase (NOS), seems to play an ambiguous role during tissue ischemia
      reperfusion injury. Our objective was to evaluate the effects of L-arginine, a NO
      donor, and N(G)-nitro-L-arginine-methylester (L-NAME), a NOS inhibitor, on
      oxidative stress, renal dysfunction, histologic alterations and surgical
      mortality rate induced by renal ischemia-reperfusion (RIR) in uninephrectomized
      rats. MATERIALS AND METHODS: One-hundred and ninety-seven Wistar rats were
      randomized into five experimental groups. Group 1: sham operation; group 2: right
      uninephrectomy (UNI); group 3: UNI + RIR in the contralateral kidney; group 4:
      UNI + L-NAME (20 mg/kg; intraperitoneally) + RIR; and group 5: UNI + L-arginine +
      RIR. The effect of the drugs was evaluated by lipid peroxidation measured by the
      renal malondialdehyde (MD) content and chemiluminescence (CL) levels, serum
      creatinine (Cr) levels, urinary volume, tubular necrosis and athrophy,
      inflammatory infiltrate, interstitial fibrosis as histologic evaluation and
      surgical mortality rate after the procedures. A P value less than 0.05 was
      considered significant. RESULTS: Right uninephrectomy did not alter the renal
      parameters. RIR increased Cr levels (at 24 and 96 h of reperfusion), index of
      lipid peroxidation (both MD and QL levels), and worsened the histologic aspects.
      Pretreatment with L-arginine reduced the kidney levels of QL when compared with
      the non-treated group (5574 +/- 909 vs. 13 660 +/- 1104 cps/mg of protein; P <
      0.05) but increased the MD levels (0.97 +/- 0.24 vs. 0.79 +/- 0.06 nmol/mg of
      protein; P < 0.05). Moreover, L-arginine attenuated the increment of Cr levels,
      inflammatory infiltrate and tubular athrophy in rats subjected to RIR (P < 0.05).
      On the other hand, pretreatment with L-NAME increased both CL (17 482 +/- 4397
      vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) and MD levels (1.16 +/- 0.11 vs.
      0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Furthermore, L-NAME worsened the
      renal dysfunction (P < 0.05) at 192 h after the RIR, and surgical mortality rates
      were similar (P > 0.05). CONCLUSION: L-arginine has a tendency to exert a
      beneficial effect on renal damage during RIR in rats. Moreover, L-NAME seems to
      worsen the renal damage by increasing the kidney-levels of CL and impairment of
      renal function probably due to reduction of NO production.

PMID- 12507400
TI  - Evaluation of peripheral blood CD4 and CD8 lymphocyte subsets, CD69 expression
      and histologic rejection grade as diagnostic markers for the presence of cardiac
      allograft rejection.
AB  - We investigated the dynamics of the CD4+ and CD8+ lymphocyte subsets, and the
      expression of activation markers in cardiac transplant recipients. We tested 132
      peripheral blood samples from 62 cardiac transplant recipients using fluorescent
      staining and flow cytometry analysis. The results were correlated with
      histological rejection grade of concurrently taken biopsies, and 5-year survival
      of the recipients. A decrease in the total T lymphocyte subset, and in CD4+
      lymphocytes was associated with higher rejection grade and lesser survival. An
      increase (5-11%) of double positive CD4+ CD8+ lymphocytes was observed; these
      were mostly CD4brightCD8dim. The CD4/CD8 ratio was significantly (P < 0.00) lower
      in the transplant recipients than in normal individuals. CD69 expression was
      higher than CD54 and CD154 expression on CD4 and CD8 lymphocytes of cardiac
      transplant recipients; correlation between these activation markers was excellent
      (P < 0.001). Fluorescent staining for CD69 was often of low intensity. Multiple
      regression for % CD8+ CD69+ cells and survival, and for % CD69+ T cells and
      rejection grade yielded a significant correlation (P < 0.050). Both % CD8+ CD69+
      and % CD69+ T cells were significantly higher in samples with severe and moderate
      rejection grade (grades 3A, 3B and 4) than in samples which showed no, minimal or
      mild rejection (grades < or = 2); P-values were 0.052 and 0.003, respectively.
      Preliminary results indicated that false negative results could be contributed to
      increased immunosuppression. We conclude that CD69 expression on circulating CD4
      and CD8 lymphocytes is a useful parameter for the diagnosis of moderate and
      severe rejection.

PMID- 12507401
TI  - FasL-transfected endothelial cells decrease the proliferative response of
      allogeneic PBL.
AB  - Graft endothelium has a key role in organ transplantation because it regulates
      graft infiltration by allogeneic activated T cells. Overexpression of death
      molecules that could induce apoptosis of alloreactive T cells might be an
      alternative to the immunosuppressive treatment currently used in graft
      transplantation. Several studies have shown that immune-privileged sites express
      Fas ligand (FasL) and induce apoptosis of activated T-cells. We propose that
      endothelial cells engineered to express FasL could inhibit alloreactive T cell
      proliferation by inducing apoptosis. An expression vector was constructed with
      human FasL cDNA and used to transfect an endothelial cell line (ECV304 cells). We
      demonstrated that FasL-transfected ECV304 cells were effective in inducing
      apoptosis of Jurkat T cell lymphoma as an agonist anti-Fas antibody. Using a
      mixed lymphocyte-endothelial cell culture model we observed that FasL-transfected
      ECV304 cells which conserved their two principal costimulatory pathways inhibited
      alloreactive T cell-proliferation by inducing activated T-cell apoptosis. These
      results suggest that endothelial cells could be interesting candidates to convey
      a death signal and induce hyporesponsiveness of alloreactive T cells during organ
      transplantation.

PMID- 12507402
TI  - Alveolar neutrophilia is a predictor for the bronchiolitis obliterans syndrome,
      and increases with degree of severity.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a common complication of
      lung transplantation (LT), associated with a tremendous mortality and morbidity.
      Recent innovative research has focused on bronchoalveolar lavage (BAL) analysis,
      assuming that neutrophilia might be a marker of chronic rejection. PATIENTS AND
      METHODS: To address this issue, we retrospectively analyzed 258 sequential BAL
      from 44 lung transplant recipients, having survived for more than 3 months after
      surgery. RESULTS: At the end of the follow-up, 22, 7, 7 and 8 patients had BOS
      stage 0, 1, 2 and 3, respectively. The total cell count and neutrophilia
      increased with BOS severity (P < 0.01). BOS occuring before and after the 12th
      month of LT were associated with early and more delayed increases of BAL
      neutrophils, respectively. Finally, the various kinetic profiles of neutrophil
      progression were identified, allowing for an earlier identification of BOS stages
      2 and 3, by 3 and 6 months, respectively. Conversely, neutrophilia associated to
      BOS stage 1 remained low, and could not be distinguished from that of stage 0.
      CONCLUSIONS: These results support the possible role of neutrophils in BOS
      pathogenesis, and may be of interest for an earlier detection and management of
      chronic rejection.

PMID- 12507403
TI  - Cytokine gene expression by alloactivated cells in SCID mice.
AB  - OBJECTIVES: The severe combined immune deficient (SCID) mouse provides a neutral
      environment to study human immune responses. We therefore tested human gene
      expression of Interleukin (IL) 2, 4 and 10, interferon gamma (IFNgamma);
      transforming growth factor beta 1 (TGFbeta1); and CD40 ligand (CD40L) in splenic
      extracts of SCID mice after engraftment of PBLs from two persons (direct MLR) or
      one person plus allopeptides (indirect MLR) in the presence or absence of
      cyclosporin A (CsA) or FK506. METHODS: Cytokine gene expression was detected by
      RT and quantitative (for IFN-gamma, TGFbeta1 and CD40L) PCR. All cells,
      allopeptides, CsA (25 mg/kg/day for 7 days) or FK 506 (0.5 mg/kg/day for 7 days)
      were administered intraperitoneally (IP). RESULTS: In both direct and indirect
      MLR the numbers of SCID mice expressing the human cytokine genes varied between
      33% for IL4 and 100% for IL10, IFN-gamma, TGFbeta1, and CD40L. There was
      significant interpersonal variation in levels of gene expression. Concomitant CsA
      or FK506 administration for 7 days did not abrogate early or late (1 week after
      discontinuation of CsA or FK506) cytokine gene expression in either the direct or
      indirect MLR, but paradoxically enhanced levels of IFN-gamma, TGFbeta1 and CD40L
      gene expression in some experiments. CONCLUSIONS: The results explain late
      rejection after rapid calcineurin inhibitor withdrawal or reduction, and
      illustrate the potential use of SCID mice as a surrogate model to study graft
      outcome by determination levels of gene expression and sensitivity to
      immunosuppressive agents in the in vivo alloresponse.

PMID- 12507404
TI  - Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode
      associated with disturbed mitochondrial energy metabolism.
AB  - BACKGROUND: Hyperammonemia, hypoglycemia, hepatopathy, and ventricular
      tachycardia are common presenting features of carnitine-acylcarnitine translocase
      deficiency (Mendelian Inheritance in Man database: *212138), a mitochondrial
      fatty acid oxidation disorder with a lethal prognosis. These features have not
      been identified as the presenting features of mitochondrial cytopathy in the
      neonatal period. CASE PRESENTATION: We describe an atypical presentation of
      mitochondrial cytopathy in a 2 day-old neonate. She presented with a Reye-like
      syndrome episode, premature ventricular contractions and ventricular tachycardia.
      Initial laboratory evaluation exhibited a large amount of 3-methylglutaconic acid
      on urine organic acid analysis, mild orotic aciduria and a nonspecific abnormal
      acylcarnitine profile. The evaluation for carnitine-acylcarnitine translocase
      deficiency and other fatty acid oxidation disorders was negative. The patient
      later developed a hypertrophic cardiomyopathy and continued to be affected by
      recurrent Reye-like syndrome episodes triggered by infections. A muscle biopsy
      exhibited signs of a mitochondrial cytopathy. During the course of her disease,
      her Reye-like syndrome episodes have subsided; however, cardiomyopathy has
      persisted along with fatigue and exercise intolerance. CONCLUSIONS: This case
      illustrates that, in the neonatal period, hyperammonemia and ventricular
      tachycardia may be the presenting features of a lethal carnitine-acylcarnitine
      translocase deficiency or of a mitochondrial cytopathy, associated with a milder
      clinical course. This association broadens the spectrum of presenting phenotypes
      observed in patients with disturbed mitochondrial energy metabolism. Also, the
      presence of 3-methylglutaconic aciduria suggests mitochondrial dysfunction and
      mild orotic aciduria could potentially be used as a marker of mitochondrial
      disease.

PMID- 12507405
TI  - Neuroprotective agents for the treatment of acute ischemic stroke.
AB  - Neuroprotective treatments are therapies designed to interrupt the cellular,
      biochemical, and metabolic elaboration of injury during or following exposure to
      ischemia; they encompass a rapidly expanding array of pharmacologic
      interventions. Various classes of neuroprotective agents have reached phase III
      efficacy trials in focal ischemic stroke, but none has proven effective, despite
      successful preceding animal studies. This notwithstanding, recent favorable
      results of hypothermia in human cardiac arrest trials have validated the general
      concept of neuroprotection. In addition, the promise of neuroprotective therapy
      for focal acute ischemic stroke has been renewed by innovations in strategies of
      preclinical drug development and clinical trial design that rectify past defects,
      including trial testing of combination therapies rather than single agents and
      novel approaches to accelerating time to initiation of experimental treatment.

PMID- 12507406
TI  - Are cholesterol-lowering medications and antihypertensive agents preventing
      stroke in ways other than by controlling the risk factor?
AB  - Statins and angiotensin-converting enzyme (ACE) inhibitors are an important
      component of our armamentarium for stroke prevention. Both of these classes of
      agents have a primary mechanism of action of reducing the level of the respective
      risk factor. They also have mechanisms of action that may confer benefits beyond
      what is believed to be the primary action of the agent. This has led to
      speculation that statins reduce stroke risk by means beyond cholesterol lowering,
      and ACE inhibitors reduce stroke risk by means beyond blood pressure lowering. We
      review the mounting evidence that suggests that statins and ACE inhibitors have
      so-called pleiotropic effects that may lead to stroke prevention.

PMID- 12507407
TI  - Pregnancy and stroke.
AB  - This review details the evidence that the risk of stroke is increased in the
      peripartum and postpartum period rather than the entire 9 months of pregnancy. In
      women with prior stroke, available evidence suggests that the excess risk of a
      stroke recurrence in pregnancy is approximately 1% to 2%. Although certain
      conditions have a particularly strong association with stroke in pregnancy, such
      as eclampsia, or with the postpartum period, such as cerebral venous thrombosis,
      the clinical and therapeutic approach to women with stroke during pregnancy
      should be similar to the approach to stroke in young adults. Strategies for
      stroke prevention should take into account the competing risks to mother and
      fetus.

PMID- 12507408
TI  - Intensive care management of ischemic stroke.
AB  - The practice of neurointensive care was initially developed to manage
      postoperative neurosurgical patients and expanded thereafter to the management of
      patients with primary head trauma, intracranial hemorrhage, vasospasm after
      subarachnoid hemorrhage, elevated intracranial pressure, and unstable pulmonary
      or cardiovascular medical conditions in neurologic patients. Can neurointensive
      care with its advanced medical and neurologic resources improve the outcome of
      the ischemic stroke patient? This review discusses selection of patients
      appropriate for admission to the neurologic intensive care unit (NICU) and
      current options for the intensive care management of severe ischemic stroke and
      its attendant complications. We propose that the NICU team is well suited to
      acute stroke management if they apply their advanced skills and technologic
      resources to manage the severe stroke patient from the time of presentation to
      the emergency ward. Study is needed to determine the effect that a critical care
      level of service has on functional outcome.

PMID- 12507409
TI  - Cerebrovascular complications of alcohol and sympathomimetic drug abuse.
AB  - Alcohol abuse has been linked to intracranial hemorrhage, both intracerebral and
      subarachnoid. Some studies have found a dose-response relationship, so that
      increasing levels of abuse are associated with greater risk of hemorrhage.
      However, alcohol abuse has not been clearly linked to cerebral infarction, and
      some studies find that mild-to-moderate drinking appears to be associated with a
      decreased risk of cerebral infarction. Intravenous administration of drugs of
      abuse predisposes to endocarditis, which may lead to embolic stroke. Associations
      have been reported between various sympathomimetic drugs and cerebral infarction.
      A possible mechanism for cerebral infarction is focal arterial vasoconstriction
      and occasionally cerebral vasculitis. Associations have also been reported
      between various sympathomimetic drugs and intracranial hemorrhage. A likely
      mechanism for intracranial hemorrhage is acute arterial hypertension. With the
      exception of endocarditis, management of stroke related to drug abuse is largely
      supportive, with emphasis on supportive care to prevent stroke complications,
      physical and occupational therapy, and aggressive addiction rehabilitation.

PMID- 12507410
TI  - New strategies for prevention of ischemic stroke: the LIFE study.
AB  - New strategies to lower the risk of stroke among high-risk persons are being
      developed. Therapies such as cholesterol-lowering medications and newer
      antihypertensive agents appear to complement traditional antithrombotic drugs and
      surgical procedures. Of particular interest is the use of the newer angiotensin
      converting enzyme (ACE) inhibitors, which appear to have an effect on stabilizing
      the vascular endothelium. The Losartan Intervention For Endpoint (LIFE) reduction
      in hypertension study provides additional data to support the use of the ACE
      inhibitors to lower the risk of stroke among patients with hypertension and
      vascular diseases.

PMID- 12507411
TI  - Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia
      gravis.

PMID- 12507412
TI  - Pilot trial of albuterol in spinal muscular atrophy.

PMID- 12507413
TI  - Current concepts and controversy in chronic inflammatory demyelinating
      polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune
      mediated demyelinating neuropathy. It is the most common treatable acquired
      polyneuropathy and represents a significant number of initially undiagnosed
      neuropathy patients. This article reviews the common clinical, laboratory, and
      electrodiagnostic features of CIDP. In addition, current areas of uncertainty are
      discussed.

PMID- 12507414
TI  - Autophagic vacuolar myopathies.
AB  - Hereditary myopathies characterized by the development of autophagic vacuoles can
      be categorized into three groups: rimmed vacuolar myopathies, acid maltase
      deficiency (glycogen storage disease type II), and myopathies characterized by
      the autophagic vacuoles with unique vacuolar membranes. Rimmed vacuolar
      myopathies are most likely secondary lysosomal myopathies because all of the
      identified causative genes encode extralysosomal proteins. Deficiency of acid
      maltase, a lysosomal enzyme, has been well characterized clinically,
      pathologically, biochemically, and genetically, and may become treatable in the
      near future. The diseases in the last category are relatively rare, but appear to
      be genetically heterogeneous and the list of these diseases is expanding. Danon
      disease, the best-characterized disorder in this group, is caused by primary
      deficiency of a lysosomal membrane protein, LAMP-2. Therefore, diseases in this
      category are expected to be primary lysosomal disease.

PMID- 12507415
TI  - Recent advances in amyotrophic lateral sclerosis research.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in
      adults. Despite several genetic breakthroughs, the actual cause and mechanism of
      neurodegeneration in ALS remains a mystery. Nevertheless, recent scientific and
      clinical advances have led to the development of new therapeutic strategies for
      this progressive, fatal disorder. We review the progress of the most recent
      clinical trials in ALS, taking into account some of the hurdles encountered by
      these studies. We also discuss the potential role of retroviral infection as a
      cause or contributor to ALS, which is one of the most recent hypotheses for the
      pathogenesis of the disease. The genetic background of ALS is summarized and
      special attention is given to the newly identified ALS gene ALS2, and to those
      that are currently being investigated. The last part of this review is dedicated
      to the mutation in superoxide dismutase-1 (SOD1). The hypothesized deleterious
      mechanisms of mutant SOD1 are discussed, as well as the possibilities that the
      mutant protein activates the apoptotic cell death process and that these
      molecular alterations can be exploited to devise experimental neuroprotective
      therapies.

PMID- 12507416
TI  - Limb-girdle muscular dystrophy.
AB  - The limb-girdle muscular dystrophies (LGMDs) are a group of muscular dystrophies
      that share a similar clinical phenotype. Despite this clinical homogeneity, at
      least 15 different genetic forms of LGMD are now known. Some of these share
      pathogenetic mechanisms with other forms of muscular dystrophy, such as the
      sarcoglycanopathies (LGMD 2C-F) and the dystrophinopathies (Duchenne and Becker
      muscular dystrophy). Some are allelic with other forms of muscular dystrophy;
      LGMD 1B is allelic with autosomal dominant Emery-Dreifuss muscular dystrophy.
      Still others introduce totally unique pathogenetic mechanisms to the study of
      muscular dystrophy. For example, LGMD 2H appears to be due to mutations affecting
      the ubiquitin-proteasome pathway. A diagnostic approach is outlined based on
      clinical features, genetics, and commercially available testing.

PMID- 12507417
TI  - Medication-induced peripheral neuropathy.
AB  - Although not very common, medication-induced neuropathy is a treatable condition
      and, therefore, is important to identify. Medications continue to grow in number
      and expand in usage; consequently, toxic neuropathy continues to be relevant to
      neurologists. Many agents have toxicities that are tolerated because the
      treatments are necessary, such as therapies for HIV and malignancy. Additional
      agents to prevent or ameliorate the toxic neuropathy are being sought and trials
      are ongoing. Certain patients, however, may be at high risk for peripheral nerve
      toxicity due to genetic factors or another underlying neuropathy. Newer drug
      delivery methods, such as viral transfection, may produce less toxicity in the
      future. The underlying pathomechanisms remain incompletely elucidated; however,
      apoptosis is emerging as an important final pathway in some forms of toxic
      neuropathy. Although most cases demonstrate acute or subacute onset after
      exposure, recent experiences with statin drugs raise the possibility of occult
      toxic causes of chronic idiopathic neuropathy.

PMID- 12507418
TI  - A web of circadian pacemakers.
AB  - The mammalian circadian timing system is composed of almost as many individual
      clocks as there are cells. These countless oscillators have to be synchronized by
      a central pacemaker to coordinate temporal physiology and behavior. Recently,
      there has been some progress in understanding the relationship and communication
      mechanisms between central and peripheral clocks.

PMID- 12507419
TI  - Taking the study of cancer cell survival to a new dimension.
AB  - Apoptosis plays a key role in the development of cancer and the response of tumor
      cells to therapeutic intervention. Recent work using three-dimensional cell
      culture models underscores the importance of the interactions between epithelial
      cells-both normal and malignant-and the extracellular matrix that surrounds them
      in informing life and death decisions. Research in this area is beginning to
      define the oncogenic pathways that can interfere with this process and the
      biochemical pathways that transmit signals from proper cell-matrix interactions
      to promote cell survival.

PMID- 12507420
TI  - Pattern recognition receptors: doubling up for the innate immune response.
AB  - Antigen presenting cells (macrophages and dendritic cells) express pattern
      recognition molecules that are thought to recognize foreign ligands during early
      phases of the immune response. The best known of these are probably the Toll-like
      receptors, but a number of other receptors are also involved. Several of these
      recognize endogenous as well as exogenous ligands, suggesting that they play a
      dual role in normal tissue function and host defense.

PMID- 12507421
TI  - SRC-1 and TIF2 control energy balance between white and brown adipose tissues.
AB  - We have explored the effects of two members of the p160 coregulator family on
      energy homeostasis. TIF2-/- mice are protected against obesity and display
      enhanced adaptive thermogenesis, whereas SRC-1-/- mice are prone to obesity due
      to reduced energy expenditure. In white adipose tissue, lack of TIF2 decreases
      PPARgamma activity and reduces fat accumulation, whereas in brown adipose tissue
      it facilitates the interaction between SRC-1 and PGC-1alpha, which induces PGC
      1alpha's thermogenic activity. Interestingly, a high-fat diet increases the
      TIF2/SRC-1 expression ratio, which may contribute to weight gain. These results
      reveal that the relative level of TIF2/SRC-1 can modulate energy metabolism.

PMID- 12507422
TI  - The cardiac mechanical stretch sensor machinery involves a Z disc complex that is
      defective in a subset of human dilated cardiomyopathy.
AB  - Muscle cells respond to mechanical stretch stimuli by triggering downstream
      signals for myocyte growth and survival. The molecular components of the muscle
      stretch sensor are unknown, and their role in muscle disease is unclear. Here, we
      present biophysical/biochemical studies in muscle LIM protein (MLP) deficient
      cardiac muscle that support a selective role for this Z disc protein in
      mechanical stretch sensing. MLP interacts with and colocalizes with telethonin (T
      cap), a titin interacting protein. Further, a human MLP mutation (W4R) associated
      with dilated cardiomyopathy (DCM) results in a marked defect in T-cap
      interaction/localization. We propose that a Z disc MLP/T-cap complex is a key
      component of the in vivo cardiomyocyte stretch sensor machinery, and that defects
      in the complex can lead to human DCM and associated heart failure.

PMID- 12507423
TI  - Structural basis of inward rectification: cytoplasmic pore of the G protein-gated
      inward rectifier GIRK1 at 1.8 A resolution.
AB  - Inward rectifier K(+) channels govern the resting membrane voltage in many cells.
      Regulation of these ion channels via G protein-coupled receptor signaling
      underlies the control of heart rate and the actions of neurotransmitters in the
      central nervous system. We have determined the protein structure formed by the
      intracellular N- and C termini of the G protein-gated inward rectifier K(+)
      channel GIRK1 at 1.8 A resolution. A cytoplasmic pore, conserved among inward
      rectifier K(+) channels, extends the ion pathway to 60 A, nearly twice the length
      of a canonical transmembrane K(+) channel. The cytoplasmic pore is lined by
      acidic and hydrophobic amino acids, creating a favorable environment for
      polyamines, which block the pore. These results explain in structural and
      chemical terms the basis of inward rectification, and they also have implications
      for G protein regulation of GIRK channels.

PMID- 12507424
TI  - The organizing principle in the formation of the T cell receptor-CD3 complex.
AB  - The T cell receptor (TCR) serves a critical function in the immune system and
      represents one of the most complex receptor structures. A striking feature is the
      presence of nine highly conserved, potentially charged residues in the
      transmembrane helices. Previous models have attempted to explain assembly based
      on pairwise interactions of these residues. Using a novel method for the
      isolation of intact radiolabeled protein complexes, we demonstrate that one basic
      and two acidic transmembrane residues are required for the assembly of each of
      the three signaling dimers with the TCR. This remarkable three-helix arrangement
      applies to all three assembly steps and represents the organizing principle for
      the formation of this intricate receptor structure.

PMID- 12507425
TI  - PKCgamma regulates syndecan-2 inside-out signaling during xenopus left-right
      development.
AB  - The transmembrane proteoglycan syndecan-2 cell nonautonomously regulates left
      right (LR) development in migrating mesoderm by an unknown mechanism, leading to
      LR asymmetric gene expression and LR orientation of the heart and gut. Here, we
      demonstrate that protein kinase C gamma (PKCgamma) mediates phosphorylation of
      the cytoplasmic domain of syndecan-2 in right, but not left, animal cap
      ectodermal cells. Notably, both phosphorylation states of syndecan-2 are
      obligatory for normal LR development, with PKCgamma-dependent phosphorylated
      syndecan-2 in right ectodermal cells and nonphosphorylated syndecan-2 in left
      cells. The ectodermal cells contact migrating mesodermal cells during early
      gastrulation, concurrent with the transmission of LR information. This precedes
      the appearance of monocilia and is one of the earliest steps of LR development.
      These results demonstrate that PKCgamma regulates the cytoplasmic phosphorylation
      of syndecan-2 and, consequently, syndecan-2-mediated inside-out signaling to
      adjacent cells.

PMID- 12507426
TI  - MEP-1 and a homolog of the NURD complex component Mi-2 act together to maintain
      germline-soma distinctions in C. elegans.
AB  - A rapid cascade of regulatory events defines the developmental fates of embryonic
      cells. However, once established, these developmental fates and the underlying
      transcriptional programs can be remarkably stable. Here, we describe two
      proteins, MEP-1 and LET-418/Mi-2, required for maintenance of somatic
      differentiation in C. elegans. In animals lacking MEP-1 and LET-418, germline
      specific genes become derepressed in somatic cells, and Polycomb group (PcG) and
      SET domain-related proteins promote this ectopic expression. MEP-1 and LET-418
      interact in vivo with the germline-protein PIE-1. Our findings support a model in
      which PIE-1 inhibits MEP-1 and associated factors to maintain the pluripotency of
      germ cells, while at later times MEP-1 and LET-418 remodel chromatin to establish
      new stage- or cell-type-specific differentiation potential.

PMID- 12507427
TI  - RNA polymerase I propagates unidirectional spreading of rDNA silent chromatin.
AB  - The ribosomal DNA (rDNA) tandem array in Saccharomyces cerevisiae induces
      transcriptional silencing of RNA polymerase II-transcribed genes. This SIR2
      dependent form of repression (rDNA silencing) also functions to limit rDNA
      recombination and is involved in life span control. In this report, we
      demonstrate that rDNA silencing spreads into the centromere-proximal unique
      sequence located downstream of RNA polymerase I (Pol I) transcription, but fails
      to enter the upstream telomere-proximal sequences. The spreading of silencing
      correlates with SIR2-dependent histone H3 and H4 deacetylation and can be
      extended by SIR2 overexpression. Surprisingly, rDNA silencing required
      transcription by RNA polymerase I and the direction of spreading was controlled
      by the direction of Pol I transcription.

PMID- 12507428
TI  - Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by
      mutations that lower ribosome affinity.
AB  - Translation initiation factor eIF5B/IF2 is a GTPase that promotes ribosomal
      subunit joining. We show that eIF5B mutations in Switch I, an element conserved
      in all GTP binding domains, impair GTP hydrolysis and general translation but not
      eIF5B subunit joining function. Intragenic suppressors of the Switch I mutation
      restore general translation, but not eIF5B GTPase activity. These suppressor
      mutations reduce the ribosome affinity of eIF5B and increase AUG skipping/leaky
      scanning. The uncoupling of translation and eIF5B GTPase activity suggests a
      regulatory rather than mechanical function for eIF5B GTP hydrolysis in
      translation initiation. The translational defect suggests eIF5B stabilizes Met
      tRNA(i)(Met) binding and that GTP hydrolysis by eIF5B is a checkpoint monitoring
      80S ribosome assembly in the final step of translation initiation.

PMID- 12507429
TI  - Directed evolution of substrate-optimized GroEL/S chaperonins.
AB  - GroEL/S chaperonin ring complexes fold many unrelated proteins. To understand the
      basis and extent of the chaperonin substrate spectrum, we used rounds of
      selection and DNA shuffling to obtain GroEL/S variants that dramatically enhanced
      folding of a single substrate-green fluorescent protein (GFP). Changes in the
      substrate-optimized chaperonins increase the polarity of the folding cavity and
      alter the ATPase cycle. These findings reveal a surprising plasticity of GroEL/S,
      which can be exploited to aid folding of recombinant proteins. Our studies also
      reveal a conflict between specialization and generalization of chaperonins as
      increased GFP folding comes at the expense of the ability of GroEL/S to fold its
      natural substrates. This conflict and the nature of the ring structure may help
      explain the evolution of cellular chaperone systems.

PMID- 12507430
TI  - Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in
      complex with ubiquitin aldehyde.
AB  - The ubiquitin-specific processing protease (UBP) family of deubiquitinating
      enzymes plays an essential role in numerous cellular processes. HAUSP, a
      representative UBP, specifically deubiquitinates and hence stabilizes the tumor
      suppressor protein p53. Here, we report the crystal structures of the 40 kDa
      catalytic core domain of HAUSP in isolation and in complex with ubiquitin
      aldehyde. These studies reveal that the UBP deubiquitinating enzymes exhibit a
      conserved three-domain architecture, comprising Fingers, Palm, and Thumb. The
      leaving ubiquitin moiety is specifically coordinated by the Fingers, with its C
      terminus placed in the active site between the Palm and the Thumb. Binding by
      ubiquitin aldehyde induces a drastic conformational change in the active site
      that realigns the catalytic triad residues for catalysis.

PMID- 12507432
TI  - Sex-related variations in serum nerve growth factor concentration in humans.
AB  - A role of nerve growth factor (NGF) in the neuro-endocrine-immune interactions
      has been recently suggested by the presence of NGF and its receptors in cells of
      the immune and endocrine systems. The improvement in the comprehension of the
      role played by NGF in humans is linked to the availability of a sensitive and
      reliable method to quantify NGF concentrations in body fluids and tissues. As a
      consequence of different methods used, normal levels of human serum NGF reported
      in the literature show wide differences. The present results indicate that ELISA
      appears very sensitive (detection limit 1.4pg/ml) and allows the discrimination
      of subtle variations of serum NGF concentrations. ELISA performed in serum
      obtained from men indicated that NGF concentration was 40.8+/-10.8pg/ml, whereas
      women showed significantly lower levels that were influenced by the menstrual
      cycle. In particular, the mean value of this neurotrophin during the follicular
      phase was 8.2+/-1.4pg/ml; the luteal phase, in turn, showed levels up to 14.4+/
      2.9pg/ml. The difference of serum NGF concentrations between the follicular and
      luteal phase in each woman was statistically significant. Differences in NGF
      concentrations between men and women (in both phases of the menstrual cycles)
      were also statistically significant. In conclusion, a possible role of sex
      steroids as modulators of NGF secretion in humans is strongly supported by the
      present paper. However, mechanisms underlying this phenomenon are still unknown.
      The evidence indicating physiological sex hormone-related variations in NGF
      levels would be of interest in view of the possible use of circulating NGF
      modifications as a laboratory biomarker in different diseases.

PMID- 12507433
TI  - The alteration of corticotropin-releasing factor (CRF) receptor immunoreactivity
      in the gerbil hippocampus and neocortex following ischemic insults.
AB  - Recently, we suggested that the ectopic expression of corticotropin-releasing
      factor (CRF) is associated with processes linked to neuronal injury and/or
      degeneration in response to an ischemic insult. However, little experimental data
      currently links the CRF receptor directly to neuronal death induced by ischemia.
      Therefore, in the present study, we investigated the temporal and spatial changes
      in CRF receptor immunoreactivity in the hippocampus and the neocortex after
      transient ischemia. CRF receptor immunoreactivity in the hippocampus was reduced
      up to 24h after ischemia insult, as compared to the sham. Interestingly, CRF
      receptor immunoreactivity disappeared in the CA1 region of the hippocampus at 4
      days in the post-ischemic group. The other regions of hippocampus maintained
      their immunoreactivities at this time point. On the other hand, in the neocortex,
      3h after transient ischemia, the CRF receptor immunoreactivity was elevated in
      regions vulnerable to ischemia. At 12h post-ischemia, its immunoreactivity had
      decreased versus the sham operated animals. These results suggest that the
      selectively ectopic expression of CRF following ischemia, which we reported
      previously, may regulate inflammatory responses. In addition, these findings also
      suggest that the mechanisms of neuronal death as mediated by CRF receptor differ
      in the hippocampus and the neocortex.

PMID- 12507434
TI  - Methionine-enkephalin and leucine-enkephalin increase interleukin-1 beta release
      in mixed glia cultures.
AB  - Interleukin-1 beta (IL-1 beta) is synthesized in the brain in response to LPS.
      Excessive IL-1 beta expression is observed in neurodegenerative diseases. The aim
      of this study was to evaluate the effects of methionine-enkephalin (ME) and
      leucine-enkephalin (LE) on the baseline and LPS-activated release of IL-1 beta in
      rat mixed glia cultures. ME and LE increased LPS-induced IL-1 beta release, which
      was not blocked by naloxone. Both ME and LE increased the baseline release of IL
      1 beta, which was completely blocked by naloxone pretreatment. Mixed glia
      cultures deprived of microglia (by shaking and incubating with L-leucine methyl
      ester) did not release IL-1 beta, which indicates microglia as a source of the
      changes in IL-1 beta release. The results of the study suggest that neurons may
      regulate glial activity through releasing enkephalins.

PMID- 12507435
TI  - Endothelium-dependent vasorelaxation and the expression of calcitonin gene
      related peptide in aged rats.
AB  - To explore the age-related change in endothelium-dependent vasorelaxation, plasma
      concentrations and the expression of calcitonin gene-related peptide (CGRP) as
      well as serum concentrations of asymmetry dimethylarginine (ADMA), male Sprague
      Dawley rats, aged 6 and 24 months were tested. The level of ADMA and CGRP in
      blood, and CGRP mRNA in dorsal root ganglia (DRG) were determined by high
      performance liquid chromatography (HPLC), radioimmunoassay or semi-quantitative
      reverse-transcription polymerase chain reaction, respectively. Vasodilator
      responses to cumulative concentrations of acetylcholine (ACh) (3 x 10(-9) - 3 x
      10(-7)M) and CGRP (3 x 10(-10) - 3 x 10(-8)M) were tested at the plateau of
      contraction in aortas rings. Vasodilator responses to ACh or CGRP at 24 months of
      age were decreased compared with 6 months. The serum concentration of ADMA at 24
      months of age was significantly increased compared with 6 months, while both
      plasma concentrations of CGRP and the expressions of alpha- and beta-CGRP mRNA
      were unchanged at two age groups. The results suggest that endothelium-dependent
      relaxation, but not concentrations and the expressions of CGRP, is decreased in
      aged rats, and the decrease in endothelium dependence of vasodilator response to
      CGRP may be related to the elevation of endogenous ADMA.

PMID- 12507436
TI  - Galanin peptide levels in hippocampus and cortex of galanin-overexpressing
      transgenic mice evaluated for cognitive performance.
AB  - Galanin-overexpressing transgenic mice (GAL-tg) generated on a dopamine beta
      hydroxylase promoter were previously shown to express high levels of galanin mRNA
      in the locus coeruleus, and to perform poorly on challenging cognitive tasks. The
      present study employed radioimmunoassay to quantitate the level of galanin
      peptide overexpression in two brain regions relevant to learning and memory, the
      hippocampus and cerebral cortex. Approximately 4-fold higher levels of galanin
      were detected in the hippocampus of GAL-tg as compared to WT. Approximately 10
      fold higher levels of galanin were detected in the frontal cortex of GAL-tg as
      compared to WT. A second cohort of GAL-tg and WT again showed high levels of
      galanin overexpression in GAL-tg as compared to WT in both brain regions.
      Correlation analyses were conducted between galanin peptide concentrations and
      behavioral scores on four learning and memory tasks: the Morris water maze,
      social transmission of food preference, standard delay fear conditioning, and
      trace fear conditioning. While some significant correlations were detected,
      neither hippocampal nor cortical galanin levels in the two cohorts of GAL-tg
      consistently correlated with performance across these diverse cognitive tasks.
      Several interpretations of these findings are discussed, including the
      possibility that a threshold level of galanin overexpression is sufficient to
      impair performance on learning and memory tasks in mice.

PMID- 12507437
TI  - Subtype selective binding properties of substituted linear melanocyte stimulating
      hormone analogues.
AB  - The melanocortin receptors are peptide binding G-protein coupled receptors that
      play a role in important physiological functions such as energy balance,
      inflammatory processes and several aspects of reproduction. In this study, we
      synthesised 11 new linear MSH analogues and tested their binding to the human MC
      receptors (MC1, MC3, MC4 and MC5) expressed in COS cells. Our results show that
      introduction of Asp in position 4 similarly affects the binding to the MC1, MC4
      and MC5 receptors, but drastically lowers the binding to the MC3 receptor. Arg(5)
      substitution shows relatively high affinity for the MC4 receptor, while the
      results also give further support for specific importance of His(6) for the MC1
      receptor. Introduction of Asp in position 10, mimicking gamma-MSH, decreased the
      affinity for the MC3 receptor in similar manner as for the MC4 receptor,
      suggesting that there are important differences in the binding conformation of
      gamma-MSH and NPD-MSH. Our results provide further information about the ligand
      binding requirements for each of the MC receptor subtypes, and highlights
      differential influence of the core residues in the MSH peptides. The data set
      also provides useful information for further calculations and modeling of MC
      receptor binders.

PMID- 12507438
TI  - Roles and perspectives of neuropeptides in medicine.

PMID- 12507439
TI  - Temporal dynamics of brain tissue nitric oxide during functional forepaw
      stimulation in rats.
AB  - We report the first dynamic measurements of tissue nitric oxide (NO) during
      functional activation of rat somatosensory cortex by electrical forepaw
      stimulation. Cortical tissue NO was measured electrochemically with rapid
      responding recessed microelectrodes (tips <10 microm). Simultaneous blood flow
      measurements were made by laser-Doppler flowmetry (LDF). NO immediately
      increased, reaching a peak 125.5 +/- 32.8 (SE) nM above baseline (P < 0.05)
      within 400 ms after stimulus onset, preceding any LDF changes, and then returned
      close to prestimulus levels after 2 s (123 signal-averaged trials, 12 rats).
      Blood flow began rising after a 1-s delay, reaching a peak just before electrical
      stimulation was ended at t = 4 s. A consistent poststimulus NO undershoot was
      observed as LDF returned to baseline. These findings complement our previous
      study (B. M. Ances et al., 2001, Neurosci. Lett. 306, 106-110) in which a
      transient decrease in rat somatosensory cortex tissue oxygen partial pressure was
      found to precede blood flow increases during functional activation.

PMID- 12507440
TI  - The evaluation of preprocessing choices in single-subject BOLD fMRI using NPAIRS
      performance metrics.
AB  - This work proposes an alternative to simulation-based receiver operating
      characteristic (ROC) analysis for assessment of fMRI data analysis methodologies.
      Specifically, we apply the rapidly developing nonparametric prediction,
      activation, influence, and reproducibility resampling (NPAIRS) framework to
      obtain cross-validation-based model performance estimates of prediction accuracy
      and global reproducibility for various degrees of model complexity. We rely on
      the concept of an analysis chain meta-model in which all parameters of the
      preprocessing steps along with the final statistical model are treated as
      estimated model parameters. Our ROC analog, then, consists of plotting prediction
      vs. reproducibility results as curves of model complexity for competing meta
      models. Two theoretical underpinnings are crucial to utilizing this new
      validation technique. First, we explore the relationship between global signal-to
      noise and our reproducibility estimates as derived previously. Second, we submit
      our model complexity curves in the prediction versus reproducibility space as
      reflecting classic bias-variance tradeoffs. Among the particular analysis chains
      considered, we found little impact in performance metrics with alignment, some
      benefit with temporal detrending, and greatest improvement with spatial
      smoothing.

PMID- 12507441
TI  - Very high-resolution morphometry using mass-preserving deformations and HAMMER
      elastic registration.
AB  - This article presents a very high-resolution voxel-based morphometric method, by
      using a mass-preserving deformation mechanism and a fully automated spatial
      normalization approach, referred to as HAMMER. By using a hierarchical attribute
      based deformation strategy, HAMMER partly overcomes limitations of several
      existing spatial normalization methods, and it achieves a level of accuracy that
      makes possible morphometric measurements of spatial specificity close to the
      voxel dimensions. The proposed method is validated by a series of experiments,
      with both simulated and real brain images.

PMID- 12507442
TI  - Cognitive and brain consequences of conflict.
AB  - Tasks involving conflict between stimulus dimensions have been shown to activate
      dorsal anterior cingulate and prefrontal areas. It has been proposed that the
      dorsal anterior cingulate is involved a domain general process of monitoring
      conflict, while prefrontal areas are involved in resolving conflict. We examine
      three tasks that all require people to respond based on one stimulus dimension
      while ignoring another conflicting dimension, but which vary in the source of
      conflict. One of the tasks uses language stimuli (Stroop effect) and two use
      nonlanguage spatial conflicts appropriate for children and nonhuman animals. In
      Experiment 1, 12 participants were studied with event-related functional magnetic
      resonance imaging (fMRI) while performing each of the three tasks. Reaction times
      for each of the three tasks were significantly longer in the incongruent
      condition compared with the congruent condition, demonstrating that each task
      elicits a conflict. By studying the same people in the same session, we test the
      hypothesis that conflict activates a similar brain network in the three tasks.
      Significant activations were found in the anterior cingulate and left prefrontal
      cortex for all three conflict tasks. Within these regions, the conflict component
      demonstrated evidence for significant common activation across the three tasks,
      although the peak activation point and spatial extent were not identical. Other
      areas demonstrated activation unique to each task. Experiments 2-4 provide
      behavioral evidence indicating considerable independence between conflict
      operations involved in the tasks. The behavioral and fMRI results taken together
      seem to argue against a single unified network for processing conflict, but
      instead support either distinct networks for each conflict task or a single
      network that monitors conflict with different sites used to resolve the conflict.

PMID- 12507443
TI  - Localization of primary auditory cortex in humans by magnetoencephalography.
AB  - Brief auditory stimuli activate the primary auditory cortex (PAC) earlier than
      any other cortical area so, within a certain latency range, the PAC is the only
      cortical source contributing to the auditory evoked field (AEF). Nevertheless,
      there is no AEF component specific to PAC that can be reliably detected in all
      individuals. The present study suggests that a peak in the first temporal
      derivative of the magnetic field at about 20 ms (dP20m) is a genuine correlate of
      PAC activity. AEFs in response to clicks presented to the right ear were recorded
      with a 37-channel axial gradiometer system positioned over the left hemisphere in
      nine normal-hearing subjects. More than 8500 stimuli were presented in each of
      two independent sessions at a rate of approximately 3/s. The dipole coordinates
      for the dP20m derived from the two sessions typically differed by only a few
      millimeters. Coregistration of the dipoles with structural magnetic resonance
      images suggests that dP20m arises from an area close to the retroinsular origin
      of Heschl's gyrus. Although the dP20m is simply the point of steepest slope on
      the well-known middle-latency peak, P30m or Pam, it would appear that dP20m and
      P30m do not have the same cortical origin. Evidence is provided that P30m
      receives major contributions from at least two distinct cortical areas, only one
      of which is PAC.

PMID- 12507444
TI  - Task-dependent modulations of cortical oscillatory activity in human subjects
      during a bimanual precision grip task.
AB  - Oscillations are a widespread feature of normal brain activity and have been
      reported at a variety of different frequencies in different neuronal systems. The
      demonstration that oscillatory activity is present in motor command signals has
      prompted renewed interest in the possible functions of synchronous oscillatory
      activity within the primate sensorimotor system. In the current study, we
      investigated task-dependent modulations in coupling between sensorimotor cortical
      oscillators during a bimanual precision grip task. The task required a hold-ramp
      hold pattern of grip force to be exerted on a compliant object with the dominant
      right hand, while maintaining a steady grip with the nondominant hand. We found
      significant task-related modulation of 15- to 30-Hz coherence between
      magnetoencephalographic (MEG) activity recorded from the left sensorimotor cortex
      and electromyographic (EMG) activity in hand muscles on the right side. This
      coherence was maximal during steady hold, but disappeared during the ramp
      movements. Interestingly coherence between the right sensorimotor MEG and left
      hand EMG showed a similar, although less deeply modulated, task-related pattern,
      even though this hand was maintaining a simple steady grip. No significant
      ipsilateral MEG-EMG coherence was observed in the 15- to 30-Hz passband for
      either hand. These results suggest that the cortical oscillators in the two
      sensorimotor cortices are independent to some degree but that they may share a
      common mechanism that attenuates the cortical power in both hemispheres in the 15
      to 30-Hz range during movements of one hand. The results are consistent with the
      hypothesis that oscillatory activity in the motor system is important in
      resetting the descending motor commands needed for changes in motor state, such
      as those that occur in the transition from movement to steady grip.

PMID- 12507445
TI  - Neural correlates of auditory perception in Williams syndrome: an fMRI study.
AB  - Williams syndrome (WS), a neurogenetic developmental disorder, is characterized
      by a rare fractionation of higher cortical functioning: selective preservation of
      certain complex faculties (language, music, face processing, and sociability) in
      contrast to marked and severe deficits in nearly every other cognitive domain
      (reasoning, spatial ability, motor coordination, arithmetic, problem solving). WS
      people are also known to suffer from hyperacusis and to experience heightened
      emotional reactions to music and certain classes of noise. We used functional
      magnetic resonance imaging to examine the neural basis of auditory processing of
      music and noise in WS patients and age-matched controls and found strikingly
      different patterns of neural organization between the groups. Those regions
      supporting music and noise processing in normal subjects were found not to be
      consistently activated in the WS participants (e.g., superior temporal and middle
      temporal gyri). Instead, the WS participants showed significantly reduced
      activation in the temporal lobes coupled with significantly greater activation in
      the right amygdala. In addition, WS participants (but not controls) showed a
      widely distributed network of activation in cortical and subcortical structures,
      including the brain stem, during music processing. Taken together with previous
      ERP and cytoarchitectonic studies, this first published report of WS using fMRI
      provides additional evidence of a different neurofunctional organization in WS
      people than normal people, which may help to explain their atypical reactions to
      sound. These results constitute an important first step in drawing out the links
      between genes, brain, cognition, and behavior in Williams syndrome.

PMID- 12507446
TI  - On bias in the estimation of autocorrelations for fMRI voxel time-series
      analysis.
AB  - For fMRI time-series analysis to be statistically valid, it is important to deal
      correctly with temporal autocorrelation in the noise. Most of the approaches in
      the literature adopt a two-stage approach in which the autocorrelation structure
      is estimated using the residuals of an initial model fit. This estimate is then
      used to "prewhiten" the data and the model before the model is refit to obtain
      final activation parameter estimates. An assumption implicit in this scheme is
      that the residuals from the initial model fit represent a realization of the
      "true" noise process. In general this assumption will not be correct as certain
      components of the noise will be removed by the model fit. In this paper we
      examine (i) the form of the bias induced by the initial model fit, (ii) methods
      of correcting for the bias, and (iii) the impact of bias correction on the model
      parameter estimates. We find that while bias correction does result in more
      accurate estimates of the correlation structure, this does not translate into
      improved estimates of the model parameters. In fact estimates of the model
      parameters and their standard errors are seen to be so accurate that we conclude
      that bias correction is unnecessary.

PMID- 12507447
TI  - Brain activations during visual search: contributions of search efficiency versus
      feature binding.
AB  - We investigated the involvement of the parietal cortex in binding features during
      visual search using functional magnetic resonance imaging. We tested 10 subjects
      in four visual search tasks across which we independently manipulated (1) the
      requirement to integrate different types of features in a stimulus (feature or
      conjunction search) and (2) the degree of search efficiency (efficient or
      inefficient). We identified brain areas that were common to all conditions of
      visual search and areas that were sensitive to the factors of efficiency and
      feature binding. Visual search engaged an extensive network of parietal, frontal,
      and occipital areas. The factor of efficiency exerted a strong influence on
      parietal activations along the intraparietal sulcus and in the superior parietal
      lobule. These regions showed a main effect of efficiency and showed a simple
      effect when inefficient conditions were compared directly with efficient pop-out
      conditions in the absence of feature binding. Furthermore, a correlation analysis
      supported a tight correspondence between posterior parietal activation and the
      slope of reaction-time search functions. Conversely, feature binding during
      efficient pop-out search was not sufficient to modulate the parietal cortex. The
      results confirm the important role of the parietal cortex in visual search, but
      suggest that feature binding is not a requirement to engage its contribution.

PMID- 12507448
TI  - Olfaction and depth of word processing: a magnetoencephalographic study.
AB  - Using a whole-cortex magnetoencephalograph, magnetic field changes were recorded
      to describe brain activities related to simultaneous visual and olfactory
      processing and to detect odor-related influences on verbal information
      processing. Words had to be either shallowly (nonsemantic) or deeply (semantic)
      encoded by healthy young subjects, each of these tasks under two different kinds
      of olfactory stimulation. After each encoding phase, word recognition performance
      was tested. First, the odor was randomly associated with some of the study words
      (simultaneous stimulation; same duration as for words) for both depths of word
      processing conditions, and second, continuous olfactory stimulation (permanent
      stimulation) was provided during the whole study phases of both depths of word
      processing conditions. The statistical analysis of the physiological data
      revealed evidence of a specific odor-induced effect depending on depth of word
      processing and kind of olfactory stimulation. Brain activity between about 250
      and 450 ms as well as between about 650 and 1000 ms after stimulus onset was
      found to vary as a function of odor delivery and depth of word processing. In
      addition, a significant effect of odor stimulation on subsequent word recognition
      performance occurred in case of simultaneous odor stimulation and semantic word
      encoding. It is interpreted that in this case, word recognition performance
      significantly decreased because of the presence of the odor during prior word
      encoding. Such a behavioral effect was missing in all other conditions. The
      present psychological and physiological findings support the idea that semantic
      word encoding is specifically affected by simultaneous olfactory information
      processing. It is concluded that this phenomenon is due to a competition with
      cortical regions related to language and olfactory information processing, as
      suggested by T. S. Lorig (1999, Neurosci. Biobehav. Rev. 23, 391-398).

PMID- 12507449
TI  - The brain's response to incidental intruded words during focal text processing.
AB  - The functional neuroanatomy associated with processing single words incidentally,
      outside focal attention, was investigated. We asked subjects (n = 15) to listen,
      focus on, and comprehend a story narrative, and then single, unrelated but
      meaningful words were intruded into the ongoing narrative. We also manipulated
      the type of intruded word, using either neutral or emotionally valent words, to
      evaluate the extent of semantic processing and a potential encoding advantage for
      one type of material. Analyses emphasized the areas of activation unique to the
      intruded words as distinguished from the narrative text. Subjects were normal,
      healthy adults (n = 15). Compared to narrative text, the intruded words were
      associated with activation in the right middle temporal gyrus (BA 39) and
      posterior cingulate/precuneus regions (BA 30, 23). We conclude that the intruded
      words did make contact with word-level lexical but not necessarily semantic
      structures in the middle temporal region. The data suggested that the intruded
      words were processed by a "nonexecutive" monitoring system implemented by a
      pairing of activation in posterior, medial structures such as the posterior
      cingulate with deactivation in brain stem structures. This pattern induced a
      shift to more passive, less effortful, nonstrategic monitoring of the words.
      Thus, attention processing, not semantic processing, changes best characterized
      the brain activation unique to the intruded words. This posterior, medial region
      is discussed as a substrate dedicated to processing a second, incidental stream
      of information and thereby providing a crucial mechanism for implementing dual
      processing of the kind examined here.

PMID- 12507450
TI  - An evaluation of the use of magnetic field maps to undistort echo-planar images.
AB  - When a head is placed in an MRI scanner, differences between the magnetic
      susceptibility of tissue, bone, and air distort the magnetic field. While some of
      the resulting inhomogeneity can be corrected by the shimming process, much of it
      cannot, and this causes distortion (sometimes referred to as geometric
      distortion) of echo-planar images (EPIs). One strategy for the correction of
      distortion is to acquire a map of the magnetic field achieved in each subject and
      then to use this to undistort their EPIs after reconstruction (). Here, we
      present five experiments to evaluate the application of such a strategy on data
      from a 3-T scanner. We show that after undistortion, the shape of EPIs is more
      similar to the true shape of the brain, and we investigate the effect of head
      movement on the efficacy of undistortion. If undistortion was applied first, it
      was found that less nonlinear warping was required to transform EPIs into a
      standard space, particularly in the phase-encode direction. We show that if SPM
      99 normalization is used to perform a nonlinear warp to standard space, the prior
      application of undistortion increases the statistical power of group studies with
      motor and auditory tasks. We show that this increase in power is due to an
      increase in the overlap of activation of different subjects. Finally, we evaluate
      where in the brain undistorting EPIs might be expected to have the
      greatesteffect, in terms both of mislocalization of activationand of a reduction
      in power. Overall, undistorting EPIs using field maps has proved extremely
      successful, improving the anatomical localization of activation and increasing
      statistical power.

PMID- 12507451
TI  - An algorithm for rapid calculation of a probabilistic functional atlas of
      subcortical structures from electrophysiological data collected during functional
      neurosurgery procedures.
AB  - The paper introduces an optimal algorithm for rapid calculation of a
      probabilistic functional atlas (PFA) of subcortical structures from data
      collected during functional neurosurgery procedures. The PFA is calculated based
      on combined intraoperative electrophysiology, pre- and intraoperative
      neuroimaging, and postoperative neurological verification. The algorithm converts
      the coordinates of the neurologically most effective contacts into probabilistic
      functional maps taking into account the geometry of a stimulating electrode. The
      PFA calculation comprises the reconstruction of the contact coordinates from two
      orthogonal projections, normalizing (warping) the contacts modeled as cylinders,
      voxelizing the contact models, calculating the atlas, and computing probability.
      In addition, an analytical representation of the PFA is formulated based on
      Gaussian modeling. The initial PFA has been calculated from the data collected
      during the treatment of 274 Parkinson's disease patients, most of them operated
      bilaterally (487 operated hemispheres). It contains the most popular stereotactic
      targets, the subthalamic nucleus, globus pallidus internus, and ventral
      intermedius nucleus. The key application of the algorithm is targeting in
      stereotactic and functional neurosurgery, and it also can be employed in human
      and animal brain research.

PMID- 12507452
TI  - Dissociable neural pathways are involved in the recognition of emotion in static
      and dynamic facial expressions.
AB  - Facial expressions of emotion powerfully influence social behavior. The
      distributed network of brain regions thought to decode these social signals has
      been empirically defined using static, usually photographic, displays of such
      expressions. Facial emotional expressions are however highly dynamic signals that
      encode the emotion message in facial action patterns. This study sought to
      determine whether the encoding of facial expressions of emotion by static or
      dynamic displays is associated with different neural correlates for their
      decoding. We used positron emission tomography to compare patterns of brain
      activity in healthy men and women during the explicit judgment of emotion
      intensity in static and dynamic facial expressions of anger and happiness.
      Compared to judgments of spatial orientation for moving neutral facial
      expressions, the judgment of anger in dynamic expressions was associated with
      increased right-lateralized activity in the medial, superior, middle, and
      inferior frontal cortex and cerebellum, while judgments of happiness were
      associated with relative activation of the cuneus, temporal cortex, and the
      middle, medial, and superior frontal cortex. In contrast, the perception of anger
      or happiness in static facial expressions activated a motor, prefrontal, and
      parietal cortical network previously shown to be involved in motor imagery. The
      direct contrast of dynamic and static expressions indicated differential
      activation of visual area V5, superior temporal sulcus, periamygdaloid cortex,
      and cerebellum for dynamic angry expressions and differential activation of area
      V5, extrastriate cortex, brain stem, and middle temporal cortical activations for
      dynamic happy expressions. Thus, a distribution of neural activations is related
      to the analysis of emotion messages in the nearly constant biological motion of
      the face and differ for angry and happy expressions. Static displays of facial
      emotional expression may represent noncanonical stimuli that are processed for
      emotion content by mental strategies and neural events distinct from their more
      ecologically relevant dynamic counterparts.

PMID- 12507453
TI  - Ipsilateral area 3b responses to median nerve somatosensory stimulation.
AB  - Magnetoencephalography investigation of the somatosensory evoked fields for
      median nerve stimulation detected ipsilateral area 3b responses in 18 hemispheres
      of 14 (1 normal subject and 13 patients with brain diseases) among 482
      consecutive subjects. The major three peaks in the ipsilateral response were
      named iP50m, iN75m, and iP100m, based on the current orientation in the
      posterior, anterior, and posterior directions and the latency of 52.7 +/- 6.2,
      74.1 +/- 9.4, and 100.2 +/- 15.8 ms (mean +/- standard deviation), respectively.
      The moment of the iP50m dipole (9.4 +/- 5.7 nAm) was significantly smaller than
      that of the N20m dipole of the contralateral response (cN20m, 27.5 +/- 10.5 nAm,
      P < 0.0001). Dipoles of iP50m and cN20m were similarly localized on the posterior
      bank of the central sulcus. iP50m in the present study had the same current
      orientation as and peak latency similar to that of the first ipsilateral primary
      somatosensory response to lip stimulation in our previous report. Therefore, the
      somatosensory afferent pathway from the hand may reach directly to the
      ipsilateral area 3b at least in part of the human population.

PMID- 12507454
TI  - Head position modulates activity in the human parietal eye fields.
AB  - For us to interact with our environment we need to know where objects are around
      us, relative to our body. In monkeys, a body-centered map of visual space is
      known to exist within the parietal eye fields. This map is formed by the
      modulation of retinal responses by gain fields to gaze position. In humans, no
      map of body-centered space has yet been discovered but clinical data suggest that
      the right parietal lobe is predominantly responsible for visuospatial function.
      Using functional MRI, we have been able to demonstrate that an area in the
      intraparietal sulcus of humans has properties very similar to the parietal eye
      fields of monkeys. This area demonstrates BOLD signal changes related to the
      visual, saccadic, and memory components of saccade tasks that are analogous to
      the visual, saccadic, and memory responses of neurons within the parietal eye
      fields of monkeys. More importantly, the amount of signal change seen in this
      region is modulated by head position relative to the body, suggesting that a gain
      field dependent body-centered representation of space exists bilaterally within
      the parietal lobes in humans.

PMID- 12507456
TI  - Retrovirus-mediated gene transfer to retinal explants.
AB  - Neural retina can be isolated from mouse embryos and maintained in culture for 2
      3 weeks. In such retinal explant cultures, precursor cells differentiate into
      neurons and glial cells and form three cellular layers, mimicking well the normal
      development. This explant culture system is suitable for genetic manipulation,
      such as retrovirus-mediated gene transfer. Retroviral vectors can efficiently
      transfer genes into retinal precursors, and the copy of the viral genome is
      precisely transmitted to the progeny of infected cells. Thus, this is an
      excellent method to change stably the phenotypes of dividing cells. It has been
      shown that retroviruses carrying transcription factor genes efficiently change
      the fates of infected cells. Bicistronic expression by retroviral vectors is
      useful to test the effects of various combinations of many transcription factors.
      With this method, the transcriptional codes for retinal cell type specification
      are now being elucidated. Thus, retrovirus-mediated gene transfer to the retinal
      explant culture system offers a powerful and unique tool to analyze the molecular
      mechanism of neural development.

PMID- 12507457
TI  - Retrovirus-mediated gene expression during chick visual system development.
AB  - The chick embryo is an excellent model for studying eye morphogenesis, retinal
      cell fate determination, and retinotectal projections due to its accessibility
      and the available molecular tools. Avian replication-competent retroviruses allow
      efficient infection of proliferating cells and stable integration of the viral
      genome, including up to 2.3kb of foreign cDNA, into the host chromosome. High
      titer retroviruses are produced by transient transfection of avian DF-1 cells
      followed by centrifugation of the culture medium. Targeted infection of the optic
      vesicle, the lens vesicle, the retina and pigmented epithelium, the periocular
      mesenchyme, and the tectum can be performed at different developmental stages in
      ovo. In addition, retroviruses can be used to transduce genes of interest into
      various ocular tissue explants or cells in vitro. Virus-mediated gene expression
      can be detected within 12h of infection. Therefore, avian replication-competent
      retroviruses serve as powerful tools to misexpress wild-type and mutant gene
      products and to study molecular mechanisms underlying vertebrate visual system
      development.

PMID- 12507458
TI  - Transgenic approaches to retinal development and function in Xenopus laevis.
AB  - The African clawed frog Xenopus laevis has long been used to study the
      development and function of the vertebrate retina. An efficient technique for
      generating transgenic Xenopus embryos, the REMI procedure, has enabled the stable
      overexpression of transgenes in developing and mature X. laevis. In the retina,
      transgenes driven by retinal-specific promoters have been used to study protein
      trafficking, circadian rhythms, and retinal degeneration. The REMI technique is
      surprisingly simple, consisting of integration of plasmid DNA into permeabilized
      sperm nuclei, followed by transplantation of these nuclei into unfertilized eggs.
      Here, we describe the reagents and steps necessary for generation of transgenic
      embryos using the REMI reaction and discuss its applications for the study of
      retinal development.

PMID- 12507459
TI  - Lipofection strategy for the study of Xenopus retinal development.
AB  - The analysis of gene function during retinal development can be addressed by
      perturbing gene expression either by inhibition or by overexpression in desired
      regions and at defined stages of development. An in vivo lipofection strategy has
      been applied for stage-specific and region-specific expression of genes in
      Xenopus retina. Due to colipofection efficiency, this strategy enables us to
      study functional interaction of genes by lipofecting multiple expression
      constructs. This lipofection technique also allows us to transfect morpholino
      oligonucleotides into retinoblasts to block gene function. We present here
      various aspects of this technique, including recent improvements and
      modifications.

PMID- 12507460
TI  - Probing teleost eye development by lens transplantation.
AB  - Experimental manipulation and other lines of evidence indicate that the lens
      plays a prominent role in the growth and differentiation of the vertebrate eye.
      Here we describe a lens transplantation method for studying the role of the lens
      in teleost eye development. The method involves three steps: (1) preparing
      embryos for the operations by embedding them in agar, (2) microsurgery with
      tungsten needles to remove the lens from a donor embryo and insert it into the
      optic cup of a host embryo lacking its own lens, and (3) a recovery period
      allowing surface ectoderm to close over the wound left by insertion of the lens
      into the host embryo. A movie illustrating the method can be found at
      http://www.life.umd.edu/labs/jeffery. A troubleshooting guide and summary of
      assays for evaluating the development of the transplanted lens and its effects on
      other eye parts, including the retina, are presented. Finally, some current
      applications of the lens transplantation method are briefly described: (1)
      determination of the autonomy of zebrafish lens mutants and (2) investigation of
      the role of the lens in eye degeneration in the cavefish Astyanax. The
      transplantation method will help characterize the mechanisms through which
      vertebrate eye development is regulated by the lens.

PMID- 12507461
TI  - Analysis of gene function in the zebrafish retina.
AB  - Mutagenesis screens in zebrafish have uncovered several hundred mutant alleles
      affecting the development of the retina and established the zebrafish as one of
      the leading models of vertebrate eye development. In addition to forward genetic
      mutagenesis approaches, gene function in the zebrafish embryo is being studied
      using several reverse genetic techniques. Some of these rely on the
      overexpression of a gene product, others take advantage of antisense
      oligonucleotides to block function of selected loci. Here we describe these
      methods in the context of the developing eye.

PMID- 12507462
TI  - Tissue culture studies of retinal development.
AB  - Because of a limited number of cell types, a series of well-described cell-type
      specific markers and a stereotyped sequence of cell development, the retina has
      been a valuable model of CNS development. Dissociated and explant cultures have
      been used to help define some of the requirements for differentiation of each
      major cell class. In addition to mixed-cell cultures it is now possible to use
      cell purification or selective growth methods to give cultures of single cell
      types. Alteration of gene expression by viral infection has proved to be a
      valuable method to help elucidate developmental pathways.

PMID- 12507463
TI  - Retinal ganglion cell differentiation in cultured mouse retinal explants.
AB  - The availability of genetically engineered mice harboring specific mutations in
      genes affecting one or more retinal cell types affords new opportunities for
      investigating the genetic regulatory mechanisms of vertebrate retina formation.
      When identifying critical regulatory genes involved in retina development it is
      often advantageous to complement in vivo analysis with in vitro characterization.
      In particular, by combining classical techniques of retinal explant culturing
      with gene transfer procedures relying on herpes simple virus (HSV) amplicon
      vectors, gain-of-function analysis with genes of interest can be performed
      quickly and efficiently. Here, details are provided for isolating and culturing
      explants containing retinal progenitor cells and for infecting the explants with
      HSV expression vectors that perturb or rescue retinal ganglion cells, the first
      cell type to differentiate in the retina. In addition, the availability of
      sensitive techniques to monitor gene expression, including detection of reporter
      gene expression using antibodies and detection of endogenous marker gene
      expression using quantitative RT-PCR, provides an effective means for comparing
      wild-type and mutant retinas from genetically engineered mice.

PMID- 12507464
TI  - Somatic gene targeting in the developing and adult mouse retina.
AB  - Retinogenesis is a developmental process that is tightly regulated both
      temporally and spatially and is therefore an excellent model system for studying
      the molecular and cellular mechanisms of neurogenesis in the central nervous
      system. Understanding of these events in vivo is greatly facilitated by the
      availability of mouse mutant models, including those with natural or targeted
      mutations and those with conditional knockout or forced expression of genes. This
      article reviews these genetic modifications and their contribution to the study
      of retinogenesis in mammals, with special emphasis on conditional gene targeting
      approaches.

PMID- 12507465
TI  - Placing ocular mutants into a functional context: a chronobiological approach.
AB  - The behavior of mammals is characterized by a 24-h cycle of rest and activity
      which is a fundamental adaption to the solar cycle of light and darkness. The
      pacemaker of this circadian clock is localized in the ventral part of the
      hypothalamus, the so-called suprachiasmatic nuclei (SCN), and is entrained by
      light signals mediated by the eye. The eye is directly connected via the
      retinohypothalamic tract (RHT) to the SCN. Light that reaches the retina elicits
      glutamate release at the synaptic terminals of the RHT and influences the neurons
      in the SCN in a manner that alters the behavioral state of the animal. A light
      pulse that reaches the retina at the beginning of the night elicits a delay of
      the clock phase, whereas a light pulse that reaches the retina at the end of the
      dark period leads to an advance of the clock phase. This advance or delay can be
      quantified by measuring the change in onset of wheel-running activity. Such
      measurements have, and continue to provide, a remarkably powerful assay of how
      light is detected and transduced to regulate circadian rhythms. The methods used
      for such measurements in mice are described in the following article.

PMID- 12507466
TI  - N-terminal acetyltransferases and sequence requirements for N-terminal
      acetylation of eukaryotic proteins.
AB  - N(alpha)-terminal acetylation occurs in the yeast Saccharomyces cerevisiae by any
      of three N-terminal acetyltransferases (NAT), NatA, NatB, and NatC, which contain
      Ard1p, Nat3p and Mak3p catalytic subunits, respectively. The N-terminal sequences
      required for N-terminal acetylation, i.e. the NatA, NatB, and NatC substrates,
      were evaluated by considering over 450 yeast proteins previously examined in
      numerous studies, and were compared to the N-terminal sequences of more than 300
      acetylated mammalian proteins. In addition, acetylated sequences of eukaryotic
      proteins were compared to the N termini of 810 eubacterial and 175 archaeal
      proteins, which are rarely acetylated. Protein orthologs of Ard1p, Nat3p and
      Mak3p were identified with the eukaryotic genomes of the sequences of model
      organisms, including Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis
      thaliana, Mus musculus and Homo sapiens. Those and other putative
      acetyltransferases were assigned by phylogenetic analysis to the following six
      protein families: Ard1p; Nat3p; Mak3p; CAM; BAA; and Nat5p. The first three
      families correspond to the catalytic subunits of three major yeast NATs; these
      orthologous proteins were identified in eukaryotes, but not in prokaryotes; the
      CAM family include mammalian orthologs of the recently described Camello1 and
      Camello2 proteins whose substrates are unknown; the BAA family comprise bacterial
      and archaeal putative acetyltransferases whose biochemical activity have not been
      characterized; and the new Nat5p family assignment was on the basis of putative
      yeast NAT, Nat5p (YOR253W). Overall patterns of N-terminal acetylated proteins
      and the orthologous genes possibly encoding NATs suggest that yeast and higher
      eukaryotes have the same systems for N-terminal acetylation.

PMID- 12507467
TI  - The location of ubiquitin in Lethocerus arthrin.
AB  - Arthrin is a ubiquitinated actin that is present in flight muscles of some
      insects. In addition, it has been found in the malaria parasite Plasmodium
      falciparum. The role of this monoubiquitylation is not clear, and it does not
      appear to be associated with proteolytic degradation. The stoichiometry of
      arthrin to actin in Lethocerus indirect flight muscle, 1:6, suggests that there
      would be one arthrin molecule for each Tm-Tn (tropomyosin-troponin) complex. The
      appearance of arthrin after tropomyosin and troponin in Drosophila development is
      consistent with the Tm-Tn complex determining which actin subunit is targeted for
      conjugation with ubiquitin. We have used a new approach of three-dimensional
      reconstruction of helical filaments, the iterative helical real space
      reconstruction method, to extract segments of homogeneous arthrin out of long
      filaments where the conformation of the ubiquitin is more heterogeneous.
      Surprisingly, the location of the ubiquitin is on the face of actin subdomain 1,
      opposite to where tropomyosin binds in the "off" state, suggesting that there
      could not be a direct interaction between the ubiquitin and the tropomyosin. It
      is possible that the troponin complex in the "on" state that is bound to one
      actin strand makes an unfavorable contact with a ubiquitin molecule attached to
      the opposite actin strand. This might be the basis for a destabilization of the
      on state at rest length. Lys118 is the most likely residue to which the ubiquitin
      is conjugated, based upon fitting atomic structures of actin and ubiquitin into
      the reconstruction.

PMID- 12507468
TI  - Determinants that target the integrase of phage HK022 into the mammalian nucleus.
AB  - The integrase (Int) protein of coliphage HK022 catalyzes the site-specific
      integration and excision of the phage into and from its Escherichia coli host
      chromosome. Int expressed from a plasmid in COS1 monkey cells is localized in the
      nucleus, as is a fusion protein between Int and the green fluorescent protein
      (GFP). Mutation analysis of the GFP-Int fusion has revealed in Int two regions of
      positively charged amino acid residues that cooperate in the nuclear
      localization. One region harbors residues Arg90 and Arg93. The other, which spans
      residues 307-340 belongs to the catalytic domain of Int, is rich in basic
      residues and is strongly conserved within the Int protein family. Being localized
      in the nucleus renders Int of HK022 as a potential recombinase for site-specific
      gene manipulations in mammals.

PMID- 12507469
TI  - Post-transcriptional regulation of the Streptomyces coelicolor stress responsive
      sigma factor, SigH, involves translational control, proteolytic processing, and
      an anti-sigma factor homolog.
AB  - The sigH gene encodes a sigma factor whose transcription is controlled by stress
      regulatory systems and the developmental program in Streptomyces coelicolor.
      Here, we describe developmentally regulated post-transcriptional control systems
      for SigH. sigH is expressed as three primary translation products, SigH
      sigma(37), SigH-sigma(51), and SigH-sigma(52). In vitro, SigH-sigma(52) was
      comparable to SigH-sigma(37) in its ability to associate with RNA polymerase core
      enzyme and specifically initiate transcription in vitro. While SigH-sigma(51/52)
      were the primary gene products observed throughout early phases of growth, their
      abundance decreased during later stages in liquid or solid phase cultures while
      levels of shorter, C-terminally encoded products increased. These included SigH
      sigma(37), a product of the downstream translational initiation site, as well as
      two proteolytic derivatives of SigH-sigma(51/52) (34kDa and 38kDa). Accumulation
      of SigH-sigma(37) and processing of SigH-sigma(51/52) into these stable 34kDa and
      38kDa derivatives correlated with morphological changes on solid medium and
      physiological maturation in liquid medium. SigH-sigma(51/52) processing did not
      occur on medium non-permissive for aerial mycelium formation or in one particular
      developmental mutant (brgA). The proteolytic activity could be detected in vitro
      using crude extracts of stationary phase cultures, but was absent from
      exponential phase cultures. prsH, the gene upstream of sigH having sequence
      similarity to known anti-sigma factors, was able to bind to, and thus presumably
      inactivate SigH-sigma(52), SigH-sigma(51), and SigH-sigma(37). We have shown
      elsewhere that prsH was conditionally required for colonial development. Thus,
      while at least one transcriptional regulator is known to bring about the
      accumulation of sigH mRNA at different times and different locations in colonies,
      the post-transcriptional processes described here regulate the activity of
      different SigH isoforms and program their temporal accumulation pattern, i.e. the
      elimination of SigH-sigma(51/52) and accumulation of SigH-sigma(37)-like
      proteins, as a function of development.

PMID- 12507470
TI  - Three-dimensional structure of FEZ-1, a monomeric subclass B3 metallo-beta
      lactamase from Fluoribacter gormanii, in native form and in complex with D
      captopril.
AB  - The beta-lactamases are involved in bacterial resistance to penicillin and
      related compounds. Members of the metallo-enzyme class are now found in many
      pathogenic bacteria and are thus becoming of major clinical importance. The
      structures of the Zn-beta-lactamase from Fluoribacter gormanii (FEZ-1) in the
      native and in the complex form are reported here. FEZ-1 is a monomeric enzyme,
      which possesses two zinc-binding sites. These structures are discussed in
      comparison with those of the tetrameric L1 enzyme produced by Stenotrophomonas
      maltophilia. From this analysis, amino acids involved in the oligomerization of
      L1 are clearly identified. Despite the similarity in fold, the active site of FEZ
      1 was found to be significantly different. Two residues, which were previously
      implicated in function, are not present in L1 or in FEZ-1. The broad-spectrum
      substrate profile of Zn-beta-lactamases arises from the rather wide active-site
      cleft, where various beta-lactam compounds can be accommodated.

PMID- 12507471
TI  - Molecular modeling of the three-dimensional structure of the bacterial RNase P
      holoenzyme.
AB  - Bacterial ribonuclease P (RNase P), an enzyme involved in tRNA maturation,
      consists of a catalytic RNA subunit and a protein cofactor. Comparative
      phylogenetic analysis and molecular modeling have been employed to derive
      secondary and tertiary structure models of the RNA subunits from Escherichia coli
      (type A) and Bacillus subtilis (type B) RNase P. The tertiary structure of the
      protein subunit of B.subtilis and Staphylococcus aureus RNase P has recently been
      determined. However, an understanding of the structure of the RNase P holoenzyme
      (i.e. the ribonucleoprotein complex) is lacking. We have now used an EDTA-Fe
      based footprinting approach to generate information about RNA-protein contact
      sites in E.coli RNase P. The footprinting data, together with results from other
      biochemical and biophysical studies, have furnished distance constraints, which
      in turn have enabled us to build three-dimensional models of both type A and B
      versions of the bacterial RNase P holoenzyme in the absence and presence of its
      precursor tRNA substrate. These models are consistent with results from previous
      studies and provide both structural and mechanistic insights into the functioning
      of this unique catalytic RNP complex.

PMID- 12507472
TI  - Lysyl-tRNA synthetase from Bacillus stearothermophilus: the Trp314 residue is
      shielded in a non-polar environment and is responsible for the fluorescence
      changes observed in the amino acid activation reaction.
AB  - Three Trp variants of lysyl-tRNA synthetase from Bacillus stearothermophilus, in
      which either one or both of the two Trp residues within the enzyme (Trp314 and
      Trp332) were substituted by a Phe residue, were produced by site-directed
      mutagenesis without appreciable loss of catalytic activity. The following two
      phenomena were observed with W332F and with the wild-type enzyme, but not with
      W314F: (1) the addition of L-lysine alone decreased the protein fluorescence of
      the enzyme, but the addition of ATP alone did not; (2) the subsequent addition of
      ATP after the addition of excess L-lysine restored the fluorescence to its
      original level. Fluorometry under various conditions and UV-absorption
      spectroscopy revealed that Trp314, which was about 20A away from the lysine
      binding site and was shielded in a non-polar environment, was solely responsible
      for the fluorescence changes of the enzyme in the L-lysine activation reaction.
      Furthermore, the microenvironmental conditions around the residue were made more
      polar upon the binding of L-lysine, though its contact with the solvent was still
      restricted. It was suggested that Trp314 was located in a less polar environment
      than was Trp332, after comparison of the wavelengths at the peaks of fluorescence
      emission and of the relative fluorescence quantum yields. Trp332 was thought,
      based on the fluorescence quenching by some perturbants and the chemical
      modification with N-bromosuccinimide, to be on the surface of the enzyme, whereas
      Trp314 was buried inside. The UV absorption difference spectra induced by the L
      lysine binding indicated that the state of Trp314, including its electrostatic
      environment, changed during the process, but Trp332 did not change. The increased
      fluorescence from Trp314 at acidic pH compared with that at neutral pH suggests
      that carboxylate(s) are in close proximity to the Trp314 residue.

PMID- 12507473
TI  - Importance of the +73/294 interaction in Escherichia coli RNase P RNA substrate
      complexes for cleavage and metal ion coordination.
AB  - We have studied an interaction, the "73/294-interaction", between residues 294 in
      M1 RNA (the catalytic subunit of Escherichia coli RNase P) and +73 in the tRNA
      precursor substrate. The 73/294-interaction is part of the "RCCA-RNase P RNA
      interaction", which anchors the 3' R(+73)CCA-motif of the substrate to M1 RNA
      (interacting residues underlined). Considering that in a large fraction of tRNA
      precursors residue +73 is base-paired to nucleotide -1 immediately 5' of the
      cleavage site, formation of the 73/294-interaction results in exposure of the
      cleavage site. We show that the nature/orientation of the 73/294-interaction is
      important for cleavage site recognition and cleavage efficiency. Our data further
      suggest that this interaction is part of a metal ion-binding site and that
      specific chemical groups are likely to act as ligands in binding of Mg(2+) or
      other divalent cations important for function. We argue that this Mg(2+) is
      involved in metal ion cooperativity in M1 RNA-mediated cleavage. Moreover, we
      suggest that the 73/294-interaction operates in concert with displacement of
      residue -1 in the substrate to ensure efficient and correct cleavage. The
      possibility that the residue at -1 binds to a specific binding surface/pocket in
      M1 RNA is discussed. Our data finally rationalize why the preferred residue at
      position 294 in M1 RNA is U.

PMID- 12507474
TI  - Functional analysis of BamHI DNA cytosine-N4 methyltransferase.
AB  - We show that the kinetic mechanism of the DNA (cytosine-N(4)-)-methyltransferase
      M.BamHI, which modifies the underlined cytosine (GGATCC), differs from cytosine
      C(5) methyltransferases, and is similar to that observed with adenine N(6)
      methyltransferases. This suggests that the obligate order of ternary complex
      assembly and disassembly depends on the type of methylation reaction. In
      contrast, the single-turnover rate of catalysis for M.BamHI (0.10s(-1)) is closer
      to the DNA (cytosine-C(5)-)-methyltransferases (0.14s(-1)) than the DNA (adenine
      N(6)-)-methyltransferases (>200s(-1)). The nucleotide flipping transition
      dominates the single-turnover constant for adenine N(6) methyltransferases, and,
      since the disruption of the guanine-cytosine base-pair is essential for both
      types of cytosine DNA methyltransferases, this transition may be a common, rate
      limiting step for methylation for these two enzyme subclasses. The similar
      overall rate of catalysis by M.BamHI and other DNA methyltransferases is
      consistent with a common rate-limiting catalytic step of product dissociation.
      Our analyses of M.BamHI provide functional insights into the relationship between
      the three different classes of DNA methyltransferases that complement both prior
      structural and evolutionary insights.

PMID- 12507475
TI  - Gene structure, dual-promoters and mRNA alternative splicing of the human and
      mouse regulator of G protein signaling GAIP/RGS19.
AB  - Here we report the gene structure and transcription regulation of the human and
      mouse G protein-signaling regulator GAIP/RGS19. The GAIP/RGS19 gene is adjacent
      to and in an opposite orientation to the opioid-receptor-like receptor 1 (ORL1)
      gene. In both human and mouse, the GAIP/RGS19 gene is composed of seven exons.
      The first two exons are under the control of two different promoters and are
      alternatively employed to start the transcription of two 5' distinctive mRNAs.
      The two promoters appear to compete with and inhibit each other. We have also
      identified in mice an alternatively spliced short GAIP/RGS19 mRNA that lacks the
      exon 2 region and utilizes an ATG in exon 3 as its translation initiation codon.
      As a result, the short GAIP/RGS19 protein does not have the N-terminal 22 amino
      acid residues of a full-length isoform. GAIP/RGS19 alternative splicing patterns
      are differentially expressed in various tissues. The mRNA alternative splicing to
      produce multiple isoforms may play a significant role in regulating the function
      and selectivity of GAIP/RGS19.

PMID- 12507476
TI  - Homoassociation of VE-cadherin follows a mechanism common to "classical"
      cadherins.
AB  - Vascular endothelial cadherin (VE-cadherin/cadherin5) is specifically expressed
      in adherens junctions of endothelial cells and exerts important functions in cell
      cell adhesion as well as signal transduction. To analyze the mechanism of VE
      cadherin homoassociation, the ectodomains CAD1-5 were connected by linker
      sequences to the N terminus of the coiled-coil domain of cartilage matrix protein
      (CMP). The chimera VECADCMP were expressed in mammalian cells. The trimeric
      coiled-coil domain leads to high intrinsic domain concentrations and multivalency
      promoting self-association. Ca(2+)-dependent homophilic association of VECADCMP
      was detected in solid phase assays and cross-linking experiments. A striking
      analogy to homoassociation of type I ("classical") cadherins like E, N or P
      cadherin was observed when interactions in VECADCMP and between these trimeric
      proteins were analyzed by electron microscopy. Ca(2+)-dependent ring-like and
      double ring-like arrangements suggest interactions between domains 1 and 2 of the
      ectodomains, which may be correlated with lateral and adhesive contacts in the
      adhesion process. Association to complexes composed of two VECADCMP molecules was
      also demonstrated by chemical cross-linking. No indication for an antiparallel
      association of VECAD ectodomains to hexameric complexes as proposed by Legrand et
      al. was found. Instead the data suggest that homoassociation of VE-cadherin
      follows the conserved mechanism of type I cadherins.

PMID- 12507477
TI  - Alternate aggregation pathways of the Alzheimer beta-amyloid peptide: Abeta
      association kinetics at endosomal pH.
AB  - The deposition of beta-amyloid peptide (Abeta) fibrils around neurons is an
      invariable feature of Alzheimer's disease and there is increasing evidence that
      fibrillar deposits and/or prefibrillar intermediates play a central role in the
      observed neurodegeneration. One site of Abeta generation is the endosomes, and we
      have investigated the kinetics of Abeta association at endosomal pH over
      physiologically relevant time frames. We have identified three distinct Abeta
      association phases that occur at rates comparable to endosomal transit times.
      Rapid formation of burst phase aggregates, larger than 200nm, was observed within
      15 seconds. Two slower association phases were detected by fluorescence resonance
      energy transfer and termed phase 1 and phase 2 aggregation reactions. At 20
      microM Abeta, pH 6, the half lives of the phase 1 and phase 2 aggregation phases
      were 3.15 minutes and 17.66 minutes, respectively. Atomic force microscopy and
      dynamic light scattering studies indicate that the burst phase aggregate is large
      and amorphous, while phase 1 and 2 aggregates are spherical with hydrodynamic
      radii around 30 nm. There is an apparent equilibrium, potentially mediated
      through a soluble Abeta intermediate, between the large burst phase aggregates
      and phase 1 and 2 spherical particles. The large burst phase aggregates form
      quickly, however, they disappear as the equilibrium shifts toward the spherical
      aggregates. These aggregated species do not contain alpha-helical or beta
      structure as determined by circular dichroism spectroscopy. However, after two
      weeks beta-structure is observed and is attributable to the insoluble portion of
      the sample. After two months, mature amyloid fibrils appear and the spherical
      aggregates are significantly diminished.

PMID- 12507478
TI  - Identification of novel interactions in HIV-1 capsid protein assembly by high
      resolution mass spectrometry.
AB  - The pleomorphic nature of the immature and mature HIV-1 virions has made it
      difficult to characterize intersubunit interactions using traditional approaches.
      While the structures of isolated domains are known, the challenge is to identify
      intersubunit interactions and thereby pack these domains into supramolecular
      structures. Using high-resolution mass spectrometry, we have measured the amide
      hydrogen exchange protection factors for the soluble capsid protein (CA) and CA
      assembled in vitro. Comparison of the protection factors as well as chemical
      crosslinking experiments has led to a map of the subunit/subunit interfaces in
      the assembled tubes. This analysis provides direct biochemical evidence for the
      homotypic N domain and C domain interactions proposed from cryo-electron
      microscopy image reconstruction of CA tubes. Most significantly, we have
      identified a previously unrecognized intersubunit N domain-C domain interaction.
      The detection of this interaction reconciles previously discrepant biophysical
      and genetic data.

PMID- 12507479
TI  - The high resolution structures of free and inhibitor-bound Trypanosoma rangeli
      sialidase and its comparison with T. cruzi trans-sialidase.
AB  - The structure of the recombinant Trypanosoma rangeli sialidase (TrSA) has been
      determined at 1.6A resolution, and the structures of its complexes with the
      transition state analog inhibitor 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid
      (DANA), Neu-5-Ac-thio-alpha(2,3)-galactoside (NATG) and N-acetylneuraminic acid
      (NANA) have been determined at 1.64A, 2.1A and 2.85A, respectively. The 3D
      structure of TrSA is essentially identical to that of the natural enzyme, except
      for the absence of covalently attached sugar at five distinct N-glycosylation
      sites. The protein exhibits a topologically rigid active site architecture that
      is unaffected by ligand binding. The overall binding of DANA to the active site
      cleft is similar to that observed for other viral and bacterial sialidases,
      dominated by the interactions of the inhibitor carboxylate with the conserved
      arginine triad. However, the interactions of the other pyranoside ring
      substituents (hydroxyl, N-acetyl and glycerol moieties) differ between
      trypanosomal, bacterial and viral sialidases, providing a structural basis for
      specific inhibitor design. Sialic acid is found to bind the enzyme with the sugar
      ring in a distorted (half-chair or boat) conformation and the 2-OH hydroxyl group
      at hydrogen bonding distance of the carboxylate of Asp60, substantiating a direct
      catalytic role for this residue. A detailed comparison of TrSA with the closely
      related structure of T.cruzi trans-sialidase (TcTS) reveals a highly conserved
      catalytic center, where subtle structural differences account for strikingly
      different enzymatic activities and inhibition properties. The structure of TrSA
      in complex with NATG shows the active site cleft occupied by a smaller compound
      which could be identified as DANA, probably the product of a hydrolytic side
      reaction. Indeed, TrSA (but not TcTS) was found to cleave O and S-linked
      sialylated substrates, further stressing the functional differences between
      trypanosomal sialidases and trans-sialidases.

PMID- 12507480
TI  - The crystal structure at 2A resolution of the Ca2+ -binding protein S100P.
AB  - S100P is a small calcium-binding protein of the S100 EF-hand-containing family of
      proteins. Elevated levels of its mRNA are reported to be associated with the
      progression to hormone independence and metastasis of prostate cancer and to be
      associated with loss of senescence in human breast epithelial cells in vitro. The
      first structure of human recombinant S100P in calcium-bound form is now reported
      at 2.0A resolution by X-ray diffraction. A flexible linker connects the two EF
      hand motifs. The protein exists as a homodimer formed by non-covalent
      interactions between large hydrophobic areas on monomeric S100P. Experiments with
      an optical biosensor to study binding parameters of the S100P monomer interaction
      showed that the association rate constant was faster in the presence of calcium
      than in their absence, whereas the dissociation rate constant was independent of
      calcium. The K(d) values were 64(+/-24)nM and 2.5(+/-0.8) microM in the presence
      and in the absence of calcium ions, respectively. Dimerization of S100P is
      demonstrated in vivo using the yeast two-hybrid system. The effect of mutation of
      specific amino acids suggests that dimerization in vivo can be affected by amino
      acids on the dimer interface and in the hydrophobic core.

PMID- 12507481
TI  - Mg2+ sensing by the Mg2+ sensor PhoQ of Salmonella enterica.
AB  - The PhoP/PhoQ two-component regulatory system governs the adaptation to low
      Mg(2+) environments and virulence in several Gram-negative species. During growth
      in low Mg(2+), the sensor PhoQ modifies the activity of the response regulator
      PhoP promoting gene transcription, whereas growth in high Mg(2+) represses
      transcription of PhoP-activated genes. The PhoQ protein harbors a periplasmic
      domain of 146 amino acid residues that binds Mg(2+) in vitro and is required for
      Mg(2+)-mediated repression in vivo. Here, we identify periplasmic mutants of the
      Salmonella PhoQ protein that allow transcription of PhoP-activated genes even
      under high Mg(2+) concentrations. When expressed in a strain harboring a PhoP
      variant that is phosphorylated from acetyl phosphate, some of the mutants failed
      to repress PhoP-promoted transcription in high Mg(2+), whereas others displayed a
      wild-type ability to do so. Mutant PhoQ proteins that allowed expression of PhoP
      activated genes in high Mg(2+) displayed a pattern of iron-mediated cleavage in
      vitro that was different from that displayed by wild-type PhoQ, indicative of
      altered Mg(2+) binding. A PhoQ protein with the conserved histidine residue
      (H277) substituted by alanine could not promote transcription of PhoP-activated
      genes in low Mg(2+) but could turn off expression in response to high Mg(2+). Our
      studies demonstrate that residues G93, W97, H120 and T156 are required for a wild
      type response to Mg(2+), and suggest that Mg(2+) binding to the periplasmic
      domain regulates several activities in the PhoQ protein.

PMID- 12507482
TI  - Repositioning about the dimer interface of the transcription regulator CooA: a
      major signal transduction pathway between the effector and DNA-binding domains.
AB  - Activation of the homodimeric transcriptional regulator CooA depends on the
      coupling of CO binding at an effector domain heme with the allosteric
      repositioning of the DNA-binding domain F-helix that promotes specific DNA
      interaction. By analogy to the homologous cAMP receptor protein (CRP), it has
      been proposed that effector binding elicits subunit reorientation about their
      coiled-coil C-helix interface, and that this effector domain reorientation
      stabilizes the active position of the DNA-binding domains. Here, we describe
      experiments in which effector-independent "CooA*" variants were selected
      following randomization of a six-residue portion of the C-helix dimerization
      domain. Subsequent activity analyses, both in vivo and in vitro, were consistent
      with a model wherein improved C-helix "leucine zipper" interactions modestly
      shifted the regulator population equilibrium towards the active conformation,
      although full activation remained CO-dependent. However, in addition to the
      improved leucine zipper, maximal CooA* activity required additional C-helix
      changes which in a WT background decreased normal CO-dependent DNA-binding 100
      fold. This seemingly paradoxical combination suggested that maximal CooA*
      activity depended both on the improved coiled-coil interactions and the
      decoupling of the signal pathway within the effector domain. Both types of C
      helix changes indicate that its repositioning is crucial for the allosteric shift
      in the inactive/active equilibrium of the DNA-binding domain.

PMID- 12507483
TI  - DNA polymerase gene sequences indicate western and forest tent caterpillar
      viruses form a new taxonomic group within baculoviruses.
AB  - Baculoviruses infect larval lepidopterans, and thus have potential value as
      microbial controls of agricultural and forest pests. Understanding their genetic
      relatedness and host specificity is relevant to the risk assessment of viral
      insecticides if non-target impacts are to be avoided. DNA polymerase gene
      sequences have been demonstrated to be useful for inferring genetic relatedness
      among dsDNA viruses. We have adopted this approach to examine the relatedness
      among natural isolates of two uncharacterized caterpillar-infecting
      baculoviruses, Malacosoma californicum pluviale nucleopolyhedrovirus (McplMNPV)
      and Malacosoma disstria nucleopolyhedrovirus (MadiMNPV), which infect two closely
      related host species with little to no cross-infectivity. We designed two
      degenerate primers (BVP1 and BVP2) based on protein motifs conserved among
      baculoviruses. McplMNPV and MadiMNPV viral DNA was obtained from naturally
      infected caterpillars collected from geographically distinct sites in the
      Southern Gulf Islands and Prince George regions of British Columbia, Canada.
      Sequencing of 0.9 kb PCR amplicons from six McplMNPV and six MadiMNPV isolates
      obtained from a total of eight sites, revealed very low nucleotide variation
      among McplMNPV isolates (99.2-100% nucleotide identity) and among MadiMNPV
      isolates (98.9-100% nucleotide identity). Greater nucleotide variation was
      observed between viral isolates from the two different caterpillar species (only
      84.7-86.1% nucleotide identity). Both maximum parsimony and maximum likelihood
      phylogenetic analyses support placement of McplMNPV and MadiMNPV in a clade that
      is distinct from other groups of baculoviruses.

PMID- 12507484
TI  - The role of resting spores in the survival of the mite-pathogenic fungus
      Neozygites floridana from Mononychellus tanajoa during dry periods in Brazil.
AB  - Survival of pathogens during long periods of unfavorable conditions can be
      critical to their ecology and to their use in biological control. In northeastern
      Brazil, the mite pathogen Neozygites floridana must survive hot and dry
      conditions between wet seasons when it infects the cassava green mite
      Mononychellus tanajoa. We report on large numbers of mite cadavers bearing
      resting spores towards the end of epizootics in mid-1995. High within-leaf
      variability indicated that local factors may be important in determining resting
      spore formation. These spores remain in the host cadaver on a leaf until the
      cadaver breaks up, whereupon the spores fall freely to the soil, there to remain
      dormant. Laboratory simulation of field conditions led to ca. 25% of mycosed
      individuals bearing resting spores. Mummies (without resting spores) kept in hot
      and dry conditions showed little or no viability within 2 months, implying no
      role for survival over extended dry periods. It is proposed that resting spores
      form the principal means by which this pathogen survives the dry season in the
      study area. This has implications for its introduction to new areas in classical
      biological control.

PMID- 12507485
TI  - Influence of the host plant on occluded virus production and lethal infectivity
      of a baculovirus.
AB  - Intra- and inter-specific effects of cotton, soybean, and clover on the time
      until death of Helicoverpa zea (Boddie) and Heliothis virescens (F.) larvae
      lethally infected with H. zea nucleopolyhedrovirus (HzSNPV) were evaluated in the
      laboratory. In the first test, on second instar only, the time until death of
      lethally infected larvae of both species differed with the plant tissues
      (vegetative or reproductive) and plant species. The total viral activity produced
      per larva in LC(50) units (occluded viral bodies (OBs) per larva/LC(50) in
      OBs/mm(2) of diet surface) was greater from H. virescens larvae fed vegetative
      than reproductive tissues of all host plants, but from H. zea virus production
      was greater only when fed vegetative tissue of soybean. In a second test that
      compared second and fourth instar H. virescens on cotton, total viral activity
      from larvae treated in both instars was greater when fed vegetative than
      reproductive tissues. Results of these tests suggest that the ability of host
      plants to influence baculovirus disease is more complex than previously believed.
      When examining the epizootic potential of a baculovirus, more attention must be
      given to the effects of the host plant on the insect-virus interactions.

PMID- 12507486
TI  - Diploidy restoration in Wolbachia-infected Muscidifurax uniraptor (Hymenoptera:
      Pteromalidae).
AB  - Thelytokous reproduction, where females produce diploid female offspring without
      fertilization, can be found in many insects. In some Hymenoptera species,
      thelytoky is induced by Wolbachia, a group of cytoplasmically inherited bacteria.
      We compare and contrast early embryonic development in the thelytokous
      parthenogenetic species Muscidifurax uniraptor with the development of
      unfertilized eggs of the closely related arrhenotokous species, Muscidifurax
      raptorellus. In the Wolbachia-infected parasitic wasp M. uniraptor, meiosis and
      the first mitotic division occur normally. Diploidy restoration is achieved
      following the completion of the first mitosis. This pattern differs in the timing
      of diploidy restoration from previously described cases of Wolbachia-associated
      thelytoky. Results presented here suggest that different cytogenetic mechanisms
      of diploidy restoration may occur in different species with Wolbachia-induced
      thelytoky.

PMID- 12507487
TI  - Hirsutella thompsonii and Metarhizium anisopliae as potential microbial control
      agents of Varroa destructor, a honey bee parasite.
AB  - The potential of Hirsutella thompsonii Fisher and Metarhizium anisopliae
      (Metschinkoff) as biological control agents of the parasitic mite, Varroa
      destructor Anderson and Trueman was evaluated in the laboratory and in
      observation hives. In the laboratory, time required for 90% cumulative mortality
      of mites (LT(90)) was 4.16 (3.98-4.42) days for H. thompsonii and 5.85 (5.48
      7.43) days for M. anisopliae at 1.1 x 10(3) conidia mm(-2). At a temperature
      (34+/-1 degrees C) similar to that of the broodnest in a honey bee colony, Apis
      mellifera L., H. thompsonii [LC(90)=9.90 x 10(1) (5.86-19.35) conidia mm(-2) at
      Day 7] and M. anisopliae [LC(90)=7.13 x 10(3) (2.80-23.45) conidia mm(-2) at Day
      7] both showed significant virulence against V. destructor. The applications of
      H. thompsonii to observation hives resulted in significant mortality of mites,
      and reduction of the number of mites per bee 21 and 42 days post-treatments. The
      treatments did not significantly affect the mite population in sealed brood.
      However, the fungus must have persisted because infected mites were still
      observed [82.97+/-(0.6)%] 42 days post-treatment. In addition, the fungus was
      found to sporulate on the host. A small percentage [2.86+/-(0.2)%] of dead mites
      found in the control hives also showed fungal infection, suggesting that adult
      bees drifted between hives and disseminated the fungus. H. thompsonii was
      harmless to the honey bees at the concentrations applied and did not have any
      deleterious effects on the fecundity of the queens. Microbial control with fungal
      pathogens provides promising new avenues for control of V. destructor and could
      be a useful component of an integrated pest management program for the honey bee
      industry.

PMID- 12507488
TI  - Virulence and site of infection of the fungus, Hirsutella thompsonii, to the
      honey bee ectoparasitic mite, Varroa destructor.
AB  - The Varroa mite, Varroa destructor, is recognized as the most serious pest of
      both managed and feral Western honey bee (Apis mellifera) in the world. The mite
      has developed resistance to fluvalinate, an acaricide used to control it in
      beehives, and fluvalinate residues have been found in the beeswax, necessitating
      an urgent need to find alternative control measures to suppress this pest.
      Accordingly, we investigated the possibility of using the fungus, Hirsutella
      thompsonii, as a biocontrol agent of the Varroa mite. Among the 9 isolates of H.
      thompsonii obtained from the University of Florida and the USDA, only the 3 USDA
      isolates (ARSEF 257, 1947 and 3323) were infectious to the Varroa mite in
      laboratory tests. The mite became infected when it was allowed to walk on a
      sporulating H. thompsonii culture for 5 min. Scanning electron micrographs
      revealed that the membranous arolium of the mite leg sucker is the focus of
      infection where the fungal conidia adhered and germinated. The infected mites
      died from mycosis, with the lethal times to kill 50% (LT(50)s) dependent on the
      fungal isolates. Thus, the LT(50)s were 52.7, 77.2, and 96.7h for isolates 3323,
      257, and 1947, respectively. Passage of H. thompsonii through Varroa mite three
      times significantly reduced the LT(50)s of isolates 257 and 1947 (P<0.05) but not
      the LT(50) of isolate 3323. The fungus did not infect the honey bee in larval,
      prepupal, pupal, and adult stages under our laboratory rearing conditions. Our
      encouraging results suggest that some isolates of H. thompsonii have the
      potential to be developed as a biocontrol agent for V. destructor. However,
      fungal infectivity against the mites under beehive conditions needs to be studied
      before any conclusion can be made.

PMID- 12507489
TI  - Detection of Thelohania solenopsae (Microsporidia: Thelohaniidae) in Solenopsis
      invicta (Hymenoptera: Formicidae) by multiplex PCR.
AB  - Oligonucleotide primer pairs were designed to unique areas of the small subunit
      (16S) rRNA gene of Thelohania solenopsae and a region of the Gp-9 gene of
      Solenopsis invicta. Multiplex PCR resulted in sensitive and specific detection of
      T. solenopsae infection of S. invicta. The T. solenopsae-specific primer pair
      only amplified DNA from T. solenopsae and T. solenopsae-infected S. invicta. This
      primer pair did not produce any amplification products from DNA preparations from
      uninfected S. invicta, seven additional species of microsporidia (including
      Vairimorpha invictae), or Mattesia spp. The Gp-9-specific primers recognized and
      amplified DNA from Solenopsis xyloni, Solenopsis richteri, Solenopsis geminata,
      the invicta/richteri hybrid, and monogyne and polygyne S. invicta, but not from
      T. solenopsae, and, as such, served as a positive control verifying successful
      DNA preparation. Multiplex PCR detected T. solenopsae in worker fire ants
      infected with as few as 5000 spores. Furthermore, multiplex PCR detected T.
      solenopsae in all developmental stages of S. invicta. However, detection could be
      made more sensitive by using only the T. solenopsae-specific primer pair; ants
      infected with as few as 10 spores were able to be discerned. Multiplex PCR
      detection of T. solenopsae offers the advantages of a positive control, a single
      PCR amplification, detection of all developmental stages, and increased
      sensitivity and specificity compared with microscopy.

PMID- 12507490
TI  - Study on the transmission of tremor disease (TD) in the Chinese mitten crab,
      Eriocheir sinensis (Crustacea: Decapoda).

PMID- 12507491
TI  - Black queen-cell virus RNA is infectious in honey bee pupae.

PMID- 12507492
TI  - Nicastrin is a resident lysosomal membrane protein.
AB  - Nicastrin has been recently identified as part of the gamma-secretase complex
      that includes presenilin and other proteins. It is involved in the degradation of
      amyloid precursor protein to produce beta-amyloid peptides which are believed to
      be central to the pathophysiology of Alzheimer's disease. Previous reports have
      localized presenilin and nicastrin to the endoplasmic reticulum. However, during
      a proteomics-based characterization of lysosomal membrane proteins, a major spot
      observed on silver-stained IEF/SDS-PAGE gels was identified by mass spectrometric
      sequencing as nicastrin. Its M(r) corresponded to the reported mature M(r) for
      nicastrin, indicating that it is stable in the lysosomal environment.
      Furthermore, protease protection assays confirmed that nicastrin is contained in
      the outer lysosomal membrane, rather than in an internalized vesicle awaiting
      degradation, and that it is properly orientated with its amino-terminus facing
      the lysosomal lumen with its carboxyl-terminus facing the cytosol. We conclude
      that nicastrin is a resident lysosomal membrane protein.

PMID- 12507493
TI  - EMI domains are widespread and reveal the probable orthologs of the
      Caenorhabditis elegans CED-1 protein.
AB  - The EMI domain, first named after its presence in proteins of the EMILIN family,
      was identified here in several metazoan proteins with various domain
      architectures, among which the mammalian NEU1/NG3 proteins and Caenorhabditis
      elegans CED-1, identified as a transmembrane receptor that mediates cell corpse
      engulfment. Functional data available for EMILIN proteins suggest that the EMI
      domain could be a protein-protein interaction module. Sequence profiles specific
      of the EMI family of domains led to identify the probable orthologs of the C.
      elegans CED-1 protein in mammals and insects, which were yet uncovered.

PMID- 12507494
TI  - Homology models of human gamma-crystallins: structural study of the extensive
      charge network in gamma-crystallins.
AB  - The lens is composed of highly stable and long-lived proteins, the crystallins
      which are divided into alpha-, beta-, and gamma-crystallins. Human gamma
      crystallins belong to the betagamma superfamily. A large number of gamma
      crystallins have been sequenced and have been found to share remarkable sequence
      homology with each other. Some of the gamma-crystallins from various sources have
      also been elucidated structurally by X-ray crystallographic or NMR spectroscopic
      experiments. Their three-dimensional structures are also similar having consisted
      of two domains each possessing two Greek key motifs. In this study we have
      constructed the comparative or homology models of the four major human gamma
      crystallins, gammaA-,gammaB-, gammaC-, and gammaD-crystallins and studied the
      charge network in these crystallins. Despite an overall structural similarity
      between these crystallins, differences in the ion pair formation do exist which
      is partly due to the differences in their primary sequence and partly due to the
      structural orientation of the neighboring amino acids. In this study, we present
      an elaborate analysis of these charged interactions and their formation or loss
      with respect to the structural changes.

PMID- 12507495
TI  - Targeted tissue oxidation in the cerebral cortex induces local prolonged
      depolarization and cortical spreading depression in the rat brain.
AB  - Spreading depression (SD) has been linked to several neurological disorders as
      epilepsy, migraine aura, trauma, and cerebral ischemia, which were also
      influenced by disorderliness of the brain redox homeostasis. To investigate
      whether local tissue oxidation directly induces SD, we oxidized a restricted
      local area of the rat cerebral cortex using photo-dynamic tissue oxidation (PDTO)
      technique and examined the cerebral blood flow (CBF) and direct current (DC)
      potential in and around the oxidized area. Intensive PDTO induced prolonged
      depolarization only in the photo-oxidized area, which led to global changes of
      CBF and DC potential: synchronous negative shifts of DC potential (with an
      amplitude of approximately 20 mV) and hyperperfusion of CBF occurred. The changes
      in DC potential and CBF spread at a rate of around 3mm/min beyond the oxidized
      area to the whole hemisphere of the cerebral cortex, indicating that intensive
      local oxidation induces SD in the rat brain.

PMID- 12507496
TI  - GATE-16 and GABARAP are authentic modifiers mediated by Apg7 and Apg3.
AB  - GATE-16, GABARAP, and LC3 are three mammalian counterparts of yeast Apg8p/Aut7p.
      Here, we show that GATE-16 and GABARAP are authentic modifiers, as is the case of
      LC3 modification. The C-terminal Phe(117) of proGATE-16 and the C-terminal
      Leu(117) of proGABARAP are post-translationally cleaved to expose an essential
      Gly(116) within GATE-16 and GABARAP, with the products designated GATE-16-I and
      GABARAP-I, respectively. The Gly(116) within GATE-16 and GABARAP are essential
      for further formation of the intermediates between them and Apg7p(C572S) and
      Apg3p(C264S). When Apg7p and Apg3p are expressed, GATE-16-I and GABARAP-I are
      modified to a secondary ubiquitin-like modified form, GATE-16-II and GABARAP-II,
      respectively. GATE-16-I and GABARAP-I, but not LC3-I, localize to membrane
      compartments before their modification. These results indicate that GATE-16 and
      GABARAP are authentic modifiers, but that they have different biochemical
      characteristics from those of LC3.

PMID- 12507497
TI  - Purification of antifreeze proteins by adsorption to ice.
AB  - Antifreeze proteins (AFPs) can protect organisms from freezing injury by
      adsorbing to ice and inhibiting its growth. We describe here a method where ice,
      grown on a cold finger, is used to selectively adsorb and purify these ice
      binding proteins from a crude mixture. Type III recombinant AFP was enriched
      approximately 50-fold after one round of partitioning into ice and purified to
      homogeneity by a second round. This method can also be used to purify non-ice
      binding proteins by linkage to AFP domains as demonstrated by the recovery of a
      50 kDa maltose-binding protein-AFP fusion from a crude lysate of Escherichia
      coli.

PMID- 12507498
TI  - Identification of p115 as a PLCgamma1-binding protein and the role of Src
      homology domains of PLCgamma1 in the vesicular transport.
AB  - In order to gain further insight into the function(s) of PLCgamma1, we tried to
      identify the binding partners that can interact with the SH223 domains of
      PLCgamma1. Immunoscreening was performed with the purified antisera that are
      specific to SH223-binding proteins. Several immunoreactive clones were identified
      as the putative binding proteins and one of them was identified as p115. p115 was
      reported to be required for transcytotic fusion and subsequent binding of the
      vesicles to the target membrane. The interaction between PLCgamma1 and p115 was
      specific to carboxyl-terminal SH2 domain and SH3 domain of PLCgamma1, and also
      confirmed by biochemical approaches such as co-immunoprecipitation, pull-down
      assay, and glycerol gradient fractionation. To further characterize the role of
      SH domains of PLCgamma1 in the vesicle transport pathway, secreted form of
      alkaline phosphatase (SEAP) reporter assay was carried out. When the SH2 and/or
      SH3 domains of PLCgamma1 were deleted, the secretion of SEAP was significantly
      reduced. These findings indicate that the SH2 and SH3 domains of PLCgamma1 may
      play a role(s) in the process of the vesicle transport via interaction with other
      vesicle-associated proteins such as p115.

PMID- 12507499
TI  - LOX-1 pathway affects the extent of myocardial ischemia-reperfusion injury.
AB  - Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was originally
      identified as a receptor for oxidized low-density lipoprotein predominantly
      expressed in endothelial cells. LOX-1 expression can be induced in cardiomyocytes
      and that activation of LOX-1 is involved in apoptosis. To investigate possible
      roles of LOX-1 in myocardial ischemia-reperfusion injury, rats were subjected to
      coronary artery ligation for 1h followed by reperfusion for 2h.
      Immunohistochemistry revealed that expression of LOX-1 in cardiac myocytes was
      induced following ischemia-reperfusion but not ischemia alone. Administration of
      anti-LOX-1 monoclonal antibody resulted in a nearly 50% reduction in myocardial
      infarction size compared with that of normal IgG or saline (P<0.05). These
      findings suggest that activation of the LOX-1 pathway is involved in determining
      the extent of myocardial ischemia-reperfusion injury and that inhibition of the
      LOX-1 pathway may provide a novel strategy for treatment of acute myocardial
      infarction in humans.

PMID- 12507500
TI  - Vasoactive intestinal contractor/endothelin-2 gene expression in the murine
      central nervous system.
AB  - Vasoactive intestinal contractor (VIC) is a member of the endothelin (ET) family.
      We have investigated the regional distribution of VIC/ET-2 and of ET-1 gene
      expression in the adult murine brain and pituitary gland. We used real-time
      quantitative reverse transcription-linked polymerase chain reaction. VIC/ET-2
      gene expression was observed at high levels in the pituitary gland and medulla
      oblongata in both the mouse and rat. Moderate to low levels of expression were
      observed in other brain regions. On the contrary, ET-1 gene expression was quite
      low in the pituitary gland in comparison with the levels observed in the cerebral
      cortex, striatum, and midbrain. Cold injury to the mouse cerebral cortex caused a
      significant decrease in VIC/ET-2 gene expression in this structure, whilst
      expression of the ET-1 gene was increased. These results suggest that VIC/ET-2
      may have certain physiological roles that differ from those of ET-1 in the brain
      and pituitary gland.

PMID- 12507501
TI  - Aberrantly expressed recoverin is functionally associated with G-protein-coupled
      receptor kinases in cancer cell lines.
AB  - Cancer-associated retinopathy (CAR) is an ocular manifestation of a
      paraneoplastic syndrome whereby immunological reactions toward recoverin (Rec), a
      retina-specific Ca(2+) binding protein, and its aberrant expression in tumor
      cells lead to the retinal degeneration. To elucidate functional roles of the
      aberrantly expression in cancer cells, we performed immunoprecipitation using
      anti-human Rec mAb. We observed co-precipitation of G-protein-coupled receptor
      kinases (GRKs) and caveolin-1 with Rec from cell lysates of 293 or SSTW cells.
      Immunocytochemistry revealed that immunoreactivities toward Rec within the cancer
      cells were almost identical to those toward GRKs and caveolin-1. The present data
      strongly suggest that aberrantly expressed Rec should be involved in the GRK
      dependent cellular regulation in cancer cells.

PMID- 12507502
TI  - Resistin release by human adipose tissue explants in primary culture.
AB  - Resistin, also known as Fizz3 or ADSF, is a protein found in murine adipose
      tissue and inflammatory lung exudates. The present studies found that resistin
      was released by explants of human adipose tissue but the release was quite
      variable ranging from 3 to 158 ng/g over 48 h. The release of resistin was 250%
      greater by explants of omental than by explants of human subcutaneous abdominal
      adipose tissue. Resistin release by adipocytes was negligible as compared to that
      by the non-fat cells of adipose tissue. Leptin formation by adipocytes was 8-fold
      greater than its formation by the non-fat cells, while the formation of PAI-1 by
      adipocytes was 38% of that by the non-fat cells. The conversion of glucose to
      lactate as well as the formation of PGE(2) and IL-8 was approximately 15% of that
      by the non-fat cells. In contrast the release of IL-6 and IL-1beta by adipocytes
      was 4-7% of that by the non-fat cells while the formation of resistin and IL-10
      by adipocytes was 2% of that by non-fat cells. The release of adiponectin by
      explants ranged from 1000 to 5000 ng/g over 48 h but did not correlate with that
      of resistin. The present data suggest that resistin release by explants of human
      adipose tissue in primary culture is largely derived from the non-fat cells
      present in the explants.

PMID- 12507503
TI  - Mammalian and yeast 14-3-3 isoforms form distinct patterns of dimers in vivo.
AB  - The 14-3-3 protein family associates with many proteins involved in intracellular
      signalling. In many cases, there is a distinct preference for a particular
      isoform(s) of 14-3-3. A specific repertoire of 14-3-3 dimer formation may
      therefore influence which of the interacting proteins could be brought together.
      We have analysed the pattern of dimer formation for two of the most abundant
      isoforms of 14-3-3, epsilon ( epsilon ) and gamma (gamma), following their stable
      expression. This revealed a distinct preference for particular dimer combinations
      that is largely independent of cellular conditions. gamma 14-3-3 occurred as
      homodimers and also formed heterodimers, mainly with epsilon 14-3-3 (In PC12 and
      Cos cells). The epsilon isoform formed heterodimers with 14-3-3 beta, gamma,
      zeta, and eta, but no homodimers were detected. The two 14-3-3 homologues, BMH1
      and BMH2 from Saccharomyces cerevisiae, were mainly heterodimers.

PMID- 12507504
TI  - Constitutive expression of hyaluronan binding protein 1 (HABP1/p32/gC1qR) in
      normal fibroblast cells perturbs its growth characteristics and induces
      apoptosis.
AB  - Hyaluronan binding protein 1 (HABP1) is a ubiquitously expressed multifunctional
      phospho-protein that interacts with a wide range of ligands and is implicated in
      cell signalling. Recently, we have reported that HABP1 is an endogenous substrate
      for MAP kinase and upon mitogenic stimulation it is translocated to the nucleus
      in a MAP kinase-dependent manner (Biochem. Biophys. Res. Commun. 291(4) (2002)
      829-837). This prompted us to investigate the role of HABP1 in cell growth or
      otherwise in low MAP kinase background. We demonstrate that HABP1, when
      overexpressed in normal rat skin fibroblasts, remained in the cytosol, primarily
      concentrated around the nuclear periphery. However, HABP1 overexpressing cells
      showed extensive vacuolation and reduced growth rate, which was corrected by
      frequent medium replenishment. Further investigation revealed that HABP1
      overexpressing cells undergo apoptosis, as detected by TUNEL assay, induction of
      Bax expression, and FACS analysis, and they failed to enter into the S-phase.
      Periodic medium supplementation prevented these cells from undergoing apoptotic
      death. We also demonstrate that upon induction of apoptosis in HeLa cells by
      cisplatin, HABP1 level is upregulated, indicating a correlation between HABP1 and
      cell death in a normal cellular environment.

PMID- 12507505
TI  - Identification of residues which regulate activity of the STE20-related kinase
      hMINK.
AB  - Activity of the STE20-related kinase hMINK was investigated. hMINK was expressed
      widely, though not ubiquitously, in human tissues; highest levels being found in
      haematopoietic tissues but also in brain, placenta, and lung. Mutagenesis
      revealed that T(191) and Y(193) in the substrate recognition loop of the
      catalytic domain were critical for kinase activity against exogenous substrates
      and autophosphorylation. A mutation on T(187) showed reduced enzymatic activity
      against exogenous substrates but retained autophosphorylation activity.
      Phosphorylation was confirmed by the use of a phospho-specific T(187) antibody.
      hMINK activated the JNK signal transduction pathway and optimal JNK activation
      occurred when the C-terminus was deleted. In addition, overexpression of the C
      terminal domain devoid of kinase activity also resulted in significant activation
      of the JNK pathway. These data suggest that hMINK requires an activation step
      that dissociates the C terminal, thereby freeing the catalytic domain to interact
      with substrates. Models for receptor-mediated activation of hMINK are discussed.

PMID- 12507506
TI  - Identification of functional domains of the Escherichia coli SeqA protein.
AB  - The Escherichia coli SeqA protein, a negative regulator of chromosomal DNA
      replication, prevents the overinitiation of replication within one cell cycle by
      binding to hemimethylated G-mA-T-C sequences in the replication origin, oriC. In
      addition to the hemimethylated DNA-binding activity, the SeqA protein has a self
      association activity, which is also considered to be essential for its regulatory
      function in replication initiation. To study the functional domains responsible
      for the DNA-binding and self-association activities, we performed a deletion
      analysis of the SeqA protein and found that the N-terminal (amino acid residues 1
      59) and the C-terminal (amino acid residues 71-181) regions form structurally
      distinct domains. The N-terminal domain, which is not involved in DNA binding,
      has the self-association activity. In contrast, the C-terminal domain, which
      lacks the self-association activity, specifically binds to the hemimethylated G
      mA-T-C sequence. Therefore, two essential SeqA activities, self-association and
      DNA-binding, are independently performed by the structurally distinct N-terminal
      and C-terminal domains, respectively.

PMID- 12507507
TI  - The complete receptor-binding domain of Clostridium difficile toxin A is required
      for endocytosis.
AB  - Clostridium difficile toxin A, the chief pathogenicity factor of the antibiotic
      associated pseudomembranous colitis, is an intracellular acting cytotoxin that
      reaches its targets, the Rho GTPases, after receptor-mediated endocytosis. The C
      terminal part, constructed of repetitive peptide elements, is thought to bind to
      a lot of carbohydrate containing receptor molecules to induce clustering and
      endocytosis. To study which part of the receptor-binding domain is in charge of
      addressing toxin A into the target cells, we studied the functional, i.e.,
      endocytosis-inducing, binding of toxin A. By a competition assay between various
      receptor-binding fragments of toxin A and the holotoxin A we found that the
      complete receptor-binding domain, encompassing the entire repetitive elements,
      but not parts of it, is necessary for binding-induced endocytosis. The receptor
      binding domain itself shows weaker competition with holotoxin A than the fragment
      consisting of receptor-binding domain plus intermediary part of the toxin. All
      toxin A fragments that compete with holotoxin A are capable of inducing their own
      endocytosis. Thus, the entire receptor-binding domain, covering the C-terminal
      third of the toxin A molecule, is responsible for cell uptake of toxin A and the
      intermediary part contributes to the correct folding and assembly of the
      repetitive domains.

PMID- 12507508
TI  - Positive coupling of atypical adenosine A3 receptors on human eosinophils to
      adenylyl cyclase.
AB  - Adenosine A(3) receptors are reported to couple negatively to adenylyl cyclase
      (AC) but their mediation of anti-inflammatory effects in human eosinophils
      prompted us to investigate their coupling to AC. The A(3)-selective agonists IB
      MECA and Cl-IB-MECA evoked a concentration-dependent generation of cAMP (EC(50),
      3.2 and 1.8 microM, respectively) and were more potent than the A(2A) agonist CGS
      21680 (EC(50)=15.4 microM) and adenosine (EC(50)=19.2 microM). The cAMP response
      was additive to that produced by forskolin (10 microM). The effect of IB-MECA was
      insensitive to A(1) and A(2A) receptor antagonists, but was antagonized by the
      A(3)-selective antagonist MRS 1220 (0.1-2.5 microM) in a competitive manner. The
      estimated K(B) of 190 nM was, however, atypical. The cyclo-oxygenase inhibitor,
      indomethacin, had no effect on the cAMP response. A general inverse relationship
      between cAMP generation and inhibition of degranulation was seen. We conclude
      that in human eosinophils, an atypical form of A(3) receptors positively coupled
      to AC may exist. The resulting cAMP generation may underlie the anti-inflammatory
      actions of A(3) agonists in eosinophils.

PMID- 12507509
TI  - Electrochemical and in vitro evaluation of the redox-properties of kynurenine
      species.
AB  - Kynurenines are formed as part of the tryptophan metabolism and are known to
      exhibit pro- and anti-oxidant activities in vitro. The mapping of these
      biological redox-systems and identification of potential in vivo targets are
      therefore of great interest in cellular physiology. Here the redox-behavior of
      different kynurenines and anthranilic acids is evaluated electrochemically and
      compared to that of simple model compounds. Electrochemical results are
      correlated with the activity of these compounds in redox-bioassays where 3
      hydroxyanthranilic acid and 3-hydroxykynurenine have significant redox-activity.
      The specific electrochemical redox-behavior of these two compounds, indicating a
      particular redox-mechanism involving the hydroxyl group, can be used to
      rationalize these findings. The results indicate that tryptophan metabolites can
      undergo a range of complex redox-reactions in vivo whose precise nature
      critically depends on structural details. As a consequence, some of the
      kynurenines have the potential to contribute to neuronal damage in brain
      disorders and stroke.

PMID- 12507510
TI  - Molecular cloning, expression, and functional characterization of a novel
      zebrafish cytosolic sulfotransferase.
AB  - By searching the zebrafish expressed sequence tag (EST) database, we have
      identified a cDNA clone encoding a putative zebrafish cytosolic sulfotransferase
      (ST). This cDNA was isolated and subjected to nucleotide sequencing. Analysis of
      the sequence data revealed that this novel zebrafish ST displays 32-35% amino
      acid sequence identity to members of all major cytosolic ST gene families.
      Therefore, this zebrafish ST, while belonging to the cytosolic ST gene
      superfamily, appears to be independent from all known constituent ST gene
      families. Recombinant zebrafish ST, expressed using the pET23c prokaryotic
      expression vector and purified from transformed Escherichia coli cells, migrated
      as a 34-kDa protein upon sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Purified zebrafish ST displayed sulfating activities toward
      dopamine and thyroid hormones (T(3) and T(4)), with a pH optimum spanning 7-9.
      The enzyme also exhibited activities toward a number of xenobiotics including
      some flavonoids, isoflavonoids, and other phenolic compounds. A thermostability
      experiment revealed the enzyme to be relatively stable over a temperature range
      between 20 and 48 degrees C. Among 10 divalent metal cations tested, Fe(++),
      Hg(++), Co(++), Zn(++), Cu(++), and Cd(++) exhibited dramatic inhibitory effects
      on the activity of the enzyme. These results constitute a first study on the
      cloning, expression, and characterization of a zebrafish cytosolic ST.

PMID- 12507511
TI  - Secreted phospholipases A2 induce the expression of chemokines in microvascular
      endothelium.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by alterations in
      microvascular permeability. In ARDS secreted phospholipase A(2) (sPLA(2)) IB and
      IIA are found to be highly upregulated. In this study, we therefore investigated
      the influence of exogenously added sPLA(2)-IB and sPLA(2)-IIA on the production
      of chemokines and adhesion molecules in lung microvascular endothelial cells
      (LMVEC). Treatment of LMVEC with sPLA(2)s resulted in a significant increase in
      the production of chemokines and adhesion molecules due to an increased
      expression of their mRNA and in an enhanced release of oleic acid. The
      upregulation of chemokines and adhesion molecules by LPS was stronger in the
      presence of sPLA(2). Activation of NF-kappaB occurred upon stimulation with
      sPLA(2). Moreover the MAPkinase pERK seems to be involved since a specific pERK
      inhibitor, e.g., U0126, but not a p38Kinase inhibitor, e.g., SB203580 prevented
      sPLA(2)-induced chemokine upregulation. Our data therefore suggest that LMVEC are
      a highly sensitive target for the direct action of extracellular sPLA(2)s.

PMID- 12507512
TI  - Cloning and characterization of a novel UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase, pp-GalNAc-T14.
AB  - A novel member of the human UDP-N-acetyl-D-galactosamine:polypeptide N
      acetylgalactosaminyltransferase (pp-GalNAc-T) gene family was cloned and
      designated pp-GalNAc-T14. This type II membrane protein contains all motifs that
      are conserved in the pp-GalNAc-T family proteins and forms a subfamily with pp
      GalNAc-T2 on the phylogenetic tree. Quantitative real time PCR analysis revealed
      significantly high expression of the pp-GalNAc-T14 transcript in kidney, although
      the transcripts were ubiquitously expressed in all tissues examined. Furthermore,
      the recombinant pp-GalNAc-T14 transferred GalNAc to a panel of mucin-derived
      peptide substrates such as Muc2, Muc5AC, Muc7, and Muc13 (-58). Our results
      provide evidence that pp-GalNAc-T14 is a new member of the pp-GalNAc-T family and
      suggest that pp-GalNAc-T14 may be involved in the O-glycosylation in kidney.

PMID- 12507513
TI  - Mucosal immunogenicity of the hepatitis B core antigen.
AB  - The hepatitis B virus (HBV) core antigen (HBcAg) is a potent immunogen in animal
      models and humans and has been used as a carrier for several antigens, however,
      the mucosal immunogenicity of HBcAg or chimeric HBcAg proteins has been poorly
      studied and only using the truncated variant of the HBcAg. In this study we
      explored the mucosal immunogenicity in mice of the recombinant complete
      nucleocapside of HBcAg. The antigen was administered by different mucosal and
      parenteral routes. The antibody response in sera was evaluated after each
      immunization and mucosal lavages were tested with the final extraction. To
      characterize the immune response, the serum IgG antibody response was tested
      during six months and also the ratio IgG2a to IgG1 was determined. The results
      obtained evidenced that the mucosal immunogenicity of HBcAg depended on the
      administration route, being the intranasal (i.n.) route the one that generated
      the higher IgG responses in sera, similar in intensity and duration to parenteral
      administrations. The IgA response in mucosal washes was superior for nasally
      immunized mice compared to the rest of mucosal and parenteral groups. The nasal
      route also induced the higher IgG2a to IgG1 ratio, evidencing a Th1-like Ab
      subclass pattern. In addition to the high Ab responses, preliminary results of
      the cellular response induced by nasal administration evidenced the induction of
      strong lymphoproliferative responses in spleen cells.

PMID- 12507514
TI  - Identification of differentially expressed genes like cofilin2 in growing
      collateral arteries.
AB  - Arteriogenesis, the growth of pre-existing collateral arteries, can be induced in
      rabbits by occlusion of the femoral artery. In order to analyze the differential
      gene expression in arteriogenesis, cDNA of collateral arteries 24h after femoral
      occlusion or sham operation was subjected to suppression subtractive
      hybridization (SSH). We demonstrated an upregulation of the U6 snRNA binding
      protein Lsm5, cytochrome b, an expressed sequence tag, and the actin
      depolymerizing factor cofilin2 mRNA in collateral arteries 24h after femoral
      ligation. For cofilin2, we also detected an increase in the protein level and a
      localization predominantly in smooth muscle cells of collaterals. Simultaneously
      with the upregulation of cofilin2 we found a downregulation of the alpha-smooth
      muscle actin mRNA in growing collateral arteries. In summary, our data showed an
      augmented expression level of genes contributing to different fundamental
      processes of arteriogenesis.

PMID- 12507515
TI  - Detection of rViscumin in plasma samples by immuno-PCR.
AB  - To allow for pharmacokinetic studies in adjunction with the current clinical
      developments of the potent cytostatic anti-cancer drug rViscumin, a sandwich
      immuno-PCR (IPCR) assay was developed for the detection of rViscumin in blood
      plasma. The IPCR was carried out with a commercially available reagent kit,
      consisting of pre-assembled rViscumin-specific antibody-DNA conjugates as well as
      a specific competitor DNA fragment to be amplified by PCR. Various combinations
      of capture- and detection-antibodies were compared for performance in IPCR. Using
      the optimized assay, as few as 50 zeptomol (approx. 100 fg/ml) rViscumin (MW 57
      kDa) was detectable in standardized human serum samples. The IPCR assay was very
      selective for rViscumin and in spiking experiments in proband plasma samples,
      signal recovery rates between 70% and 120% were obtained. The linear sensitivity
      range of the assay covered more than five orders of magnitude. Repeated
      measurements of rViscumin resulted in a mean standard deviation value of 14.2%.

PMID- 12507516
TI  - DYRK1 is a co-activator of FKHR (FOXO1a)-dependent glucose-6-phosphatase gene
      expression.
AB  - Expression of glucose-6-phosphatase (G6Pase), one of the rate-limiting enzymes of
      hepatic gluconeogenesis, has recently been shown to be transactivated by the
      transcription factor FKHR. One of the proteins known to directly interact with
      FKHR is the nuclear protein kinase DYRK1A. In order to study the effects of
      DYRK1A on G6Pase gene expression, we generated a H4IIEC3 rat hepatoma cell line
      stably expressing DYRK1A by retroviral infection. Overexpression of DYRK1A
      increased the expression of G6Pase about threefold, as determined by Northern
      blotting. In transiently transfected HepG2 cells, co-expression of DYRK1A and a
      G6Pase promoter construct increased G6Pase promoter activity about twofold. This
      effect of DYRK1A was independent of its kinase activity, since a kinase-dead
      DYRK1A mutant as well as a point mutant of the phosphorylation site of DYRK1A in
      FKHR (Ser329Ala) failed to affect the effect of DYRK1A on the G6Pase expression.
      The effect of DYRK on the G6Pase promoter activity was produced by the isoforms
      DYRK1A and DYRK1B, which are localized in the nucleus, but not by DYRK2.
      Mutations of the FKHR-binding sites in the G6Pase promoter markedly reduced the
      effect of DYRK1 on the G6Pase promoter activity. In summary, the data suggest
      that DYRK1 is a specific co-activator of FKHR, independent of its kinase
      activity.

PMID- 12507517
TI  - Specific expression of annexin III in rat-small-hepatocytes.
AB  - Small hepatocytes are cells that express characteristic phenotypes such as a high
      growth potential and differentiation capacity. In order to identify rat-small
      hepatocyte specific proteins, we separated the cellular proteins of isolated
      small and parenchymal hepatocytes by 2D polyacrylamide gel electrophoresis.
      Comparison of their profiles revealed a protein with a molecular mass of 37 kDa
      in the small hepatocytes that was not present in the parenchymal hepatocytes.
      Proteolytic peptide mass fingerprinting was used to identify the protein and it
      was found to be annexin III. The validity of the identification was confirmed by
      Western blot analysis with anti-annexin III antibody.

PMID- 12507518
TI  - Novel rice MAP kinases OsMSRMK3 and OsWJUMK1 involved in encountering diverse
      environmental stresses and developmental regulation.
AB  - We report isolation of two novel rice (Oryza sativa L.) mitogen-activated protein
      kinases (MAPKs), OsMSRMK3 (multiple stress responsive) and OsWJUMK1 (wound- and
      JA-uninducible) that most likely exist as single copy genes in its genome.
      OsMSRMK3 and OsWJUMK1 encode 369 and 569 amino acid polypeptides having the MAPK
      family signature and phosphorylation activation motifs TEY and TDY, respectively.
      Steady state mRNA analyses of these MAPKs with constitutive expression in leaves
      of two-week-old seedlings revealed that OsMSRMK3 was up-regulated upon wounding
      (by cut), jasmonic acid (JA), salicylic acid (SA), ethylene, abscisic acid,
      hydrogen peroxide (H(2)O(2)), protein phosphatase inhibitors, chitosan, high
      salt/sugar, and heavy metals, whereas OsWJUMK1 not induced by either wounding, JA
      or SA, showed up-regulation only by H(2)O(2), heavy metals, and cold stress (12
      degrees C). Moreover, these MAPKs were developmentally regulated. These results
      strongly suggest a role for OsMSRMK3 and OsWJUMK1 in both stress-signalling
      pathways and development in rice.

PMID- 12507519
TI  - Intravenous injection of naked plasmid DNA encoding hepatitis B virus (HBV)
      produces HBV and induces humoral immune response in mice.
AB  - Hepatitis B virus (HBV) infection is highly specific to primates. To cross the
      species barrier, we injected naked plasmid DNA containing a 1.5-fold-overlength
      genome of HBV into immunocompetent mice via the tail vein with acute circulatory
      overload. The injection resulted in production of viral transcripts specifically
      in the liver and expression of hepatitis B core protein in approximately 3% of
      the hepatocytes. HBV was secreted into the blood, evidenced by the presence of
      DNase I-resistant HBV sequence in fractionated serum at a density of 1.21g/ml.
      The HBV DNA positivity in the serum persisted for 1 week. Most mice became
      positive for hepatitis B surface antigen for 2 weeks and later seropositive for
      anti-hepatitis B surface antibody. This simple and efficient HBV replication
      system in mice could be useful for investigating whether viral mutations as well
      as host genetic background may affect viral replication and induction of immune
      response.

PMID- 12507520
TI  - Binding of the human homolog of the Drosophila discs large tumor suppressor
      protein to the mitochondrial ribosomal protein MRP-S34.
AB  - The human homolog of the Drosophila discs large tumor suppressor protein (hDLG)
      functions as a scaffolding protein that facilitates the transmission of diverse
      downstream signals. Here we show that hDLG interacts through its PDZ domains with
      the carboxy-terminal S/TXV motif of the mitochondrial ribosomal protein S-34 (MRP
      S34). Our results suggest that hDLG interacts with MRP-S34 prior to entry of MRP
      S34 into the mitochondria and may be involved in the trafficking of MRP-S34.

PMID- 12507521
TI  - Synthesis of retinoid vitamin A-vitamin B6 conjugate analogues for antiviral
      chemotherapy.
AB  - The synthesis of retinoid vitamin A-vitamin B(6) conjugate analogues from a
      vitamin B(6) coenzyme analogue and putative HIV-1 trans-activating
      transcriptional regulatory protein Tat antagonist (Z)-5(')-O-phosphono
      pyridoxylidenerhodanine (B6PR) monosodium salt hemiheptadecahydrate [(Z)
      B6PRNa8.5H(2)O] is discussed here. All-trans-retinoic acid (ATRA) is coupled to
      B6PR by a modified Stork enamine acylation. It results in a product library of
      more than eight compounds, each with at least one intact all-trans or 13-cis
      vitamin A double bond system. This yellow oily concentrate mixture was subjected
      to matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass
      spectrometry (MS), UV/VIS-spectrophotometry, and proton nuclear magnetic
      resonance spectroscopy (1H-NMR). The chemical structures of six components of the
      concentrate mixture could be established by combination of these analytical
      methods. The two main components are 65% 2(')C,3O-(all-trans-retinylidyne)B6PT
      (B6RA) and 25% 2(')C-(all-trans-retinoyl)B6PT, chemically derived from (5RS)-5
      (5(')-O-phosphono-pyridoxyl)-2,4-thiazolidinedione (B6PT). This new retinoid
      selection could be of further interest in antiviral applications, especially
      treating conditions caused by RNA viruses like HIV.

PMID- 12507522
TI  - Cloning and identification of a novel human ubiquitin-like protein, DC-UbP, from
      dendritic cells.
AB  - Several ubiquitin-like proteins recently discovered have been confirmed to modify
      proteins akin to ubiquitinization for fine-regulation of intracellular proteins.
      In the present study, we report a novel ubiquitin-like protein from human
      dendritic cells (DC), named as dendritic cell-derived ubiquitin-like protein (DC
      UbP). The full-length of DC-UbP cDNA is 565bp and encodes 106 amino acids.
      Ubiquitin domain (UBQ) in DC-UbP shares 28.6% identity and 55% similarity to
      ubiquitin, but does not possess the conserved C-terminus Gly-Gly of ubiquitin
      required for ubiquitinization. DC-UbP localized in cytoplasm, especially in
      mitochondrion, indicating that it may play a role in mitochondrial biology. DC
      UbP mRNA was expressed in various tumor cells, but not in adult human normal
      tissues, suggesting that DC-UbP might be related to tumor genesis. In addition,
      DC-UbP mRNA expression decreased in the HL60 cells undergoing apoptosis after
      being stimulated with TRAIL and in the differentiated HL60 cells induced by ARTA.
      Taken together, DC-UbP might be downregulated during cellular differentiation and
      apoptosis.

PMID- 12507523
TI  - School spirits: alcohol and collegiate sports fans.
AB  - While studies have addressed alcohol use and related problems among college
      athletes, little is known about the drinking patterns of non-athletes who are
      sports fans. This study examines the relationship between alcohol use and
      interest in collegiate sports on two levels. First, do sports fans in college
      binge drink more and exhibit more negative alcohol-related outcomes than other
      students? Second, do colleges with large numbers of sports fans have higher rates
      of heavy drinking and accompanying secondhand effects affecting other students?
      The study analyzed the responses of a nationally representative sample of
      students who completed questionnaires in the spring of 1999 regarding their
      extracurricular activities and substance use. The responses of 3445 student
      sports fans were compared to those of 8405 students who were not sports fans.
      More sports fans drank alcohol, engaged in binge drinking, had a heavy drinking
      style and reported alcohol-related problems than nonfans. The percentage of
      sports fans at a school was associated with binge drinking rates and the
      secondhand effects. The implications for those working with college athletics and
      for alcohol prevention personnel are discussed.

PMID- 12507524
TI  - Hope as a predictor of entering substance abuse treatment.
AB  - Identification of characteristics that predict entry into substance abuse
      treatment programs may facilitate efforts to make effective programs more
      attractive to people who could benefit from them. We examined dispositional hope
      as a predictor of entering a voluntary substance abuse treatment program for
      federal prison inmates. Controlling statistically for demographics, comorbid
      diagnoses, and drug-use history, increased hope was associated with lower
      probability of entering treatment. Discussion focused on the possibility that in
      the context of incarceration and substance abuse, high levels of hope may serve
      as a marker of excessive self-reliance and underestimation of the need for
      professional treatment.

PMID- 12507525
TI  - Preventing underage drinking: a "roll of the dice".
AB  - This study examines the efficacy of a video entitled "Underage Drinking: A Roll
      of the Dice," and accompanying discussion guide. The video illustrates the civil
      and criminal consequences of underage drinking. The video and discussion aimed
      to: (1) increase awareness about the problem of underage drinking; (2) increase
      viewers' and participants' knowledge and perceptions of the risks and
      responsibilities and reduce the perceived acceptability of underage drinking; and
      (3) encourage discussion between youths and adults about underage drinking. The
      "Roll of the Dice" was evaluated in 19 school and community groups in Hawaii.
      Groups were randomly assigned to receive follow-up materials or no follow-up
      materials. Evaluation involved three surveys: pretest, posttest, and follow-up.
      Three hundred youths and adults responded to the first two surveys, and 220
      people completed a third survey. Youths and adults showed increases in short-term
      knowledge, perceived risk, and perceived responsibility, and a decrease in
      perceived acceptability of underage drinking after viewing the video. Significant
      improvement between the pretest and follow-up was observed, although the changes
      were not entirely maintained at the time of the posttest. The results showed that
      legal consequences of underage drinking are not common knowledge, and that a well
      designed one-time program can make a difference. This video and discussion
      session provide an inexpensive way to raise adults' and youths' awareness of the
      laws and penalties, resulting in effects maintained for at least a month after
      the program. Additional follow-up materials did not enhance retention of changes
      in knowledge and attitudes.

PMID- 12507526
TI  - Youths' exposure to environmental tobacco smoke (ETS): associations with health
      beliefs and social pressure.
AB  - Youths' exposure to environmental tobacco smoke (ETS) is a significant public
      health problem in the United States. This study examined the associations between
      health beliefs, social pressure, and exposure to ETS among high school youth.
      Data were collected in 65 schools in 18 California counties during the 1996-1997
      school year as part of the Independent Evaluation of the California Tobacco
      Control, Prevention, and Education Program. The total sample (N = 6902)
      represents 10th grade California youth attending public schools. The multiple
      group analysis approach of structural equation modeling (SEM) was employed to
      test the associations of five constructs of the health belief model (HBM) and one
      construct of perceived social pressure with ETS exposure among nonsmokers and
      smokers. Results demonstrated that high perceived susceptibility to disease was
      significantly associated with lower levels of ETS exposure for both nonsmokers
      (beta = -0.11, P < .01) and smokers (beta = -0.20, P < .01). High social pressure
      to smoke was significantly associated with higher exposure to ETS for both
      nonsmokers (beta = 0.30, P < .01) and smokers (beta = 0.41, P < .01). Perceived
      barriers predicted lower exposure to ETS for nonsmokers (beta = -0.09, P < .01)
      but higher exposure for smokers (beta = 0.11, P < .01). Cues to action and self
      efficacy were not significantly associated with ETS exposure among nonsmokers or
      smokers. These findings underscore the need to increase the awareness of harms
      associated with second hand smoke and alter social pressure, to minimize exposure
      to ETS.

PMID- 12507527
TI  - Relationships between cigarette smoking during pregnancy, gestational age,
      maternal weight gain, and infant birthweight.
AB  - OBJECTIVE: To estimate the effect of smoking on infant birthweight independent of
      gestational age and maternal weight gain during pregnancy. METHODS: Stepwise
      regression was used to identify sets of maternal and infant characteristics not
      modified by prenatal smoking that were predictors of infant birthweight,
      gestational age, and net maternal weight gain. These were then included in
      regression analyses to assess the effects of smoking, as measured by cigarette
      consumption, exhaled carbon monoxide, or urinary cotinine on gestational age, net
      maternal weight gain, and infant birthweight. RESULTS: After adjustment for
      nonmodifiable factors, smoking accounted for 1.5-3.1% of the variance in
      gestational age at delivery. It accounted for 5.3-7.7% of the variance in net
      maternal weight gain after adjustment for nonmodifiable factors and gestational
      age. After adjustment for gestational age and net maternal weight gain, and the
      nonmodifiable factors, smoking accounted for 2.7-5.2% of the variance in infant
      birthweight. CONCLUSIONS: Most of the gain in infant birthweight on quitting
      smoking is due to the independent effect of smoking on fetal growth restriction,
      with much smaller gains related to increased maternal weight gain and a slightly
      longer gestational age.

PMID- 12507528
TI  - Motivation for treatment preceding and following a substance abuse program.
AB  - BACKGROUND: Motivation for treatment is generally considered a powerful predictor
      of treatment seeking and success in patients with alcohol and drug dependence
      disorders. Objective measures have seldom been used, however, to assess how
      motivation is altered during treatment, or the impact of depression/anxiety on
      motivation. METHODS: We assessed motivation using the Treatment Motivation
      Questionnaire (TMQ) in 78 male alcohol- and drug-dependent veterans immediately
      preceding and following an intensive, 2-week residential substance abuse program.
      The TMQ assesses four domains of motivation: internal motivation, external
      motivation, interpersonal help-seeking, and nonconfidence in treatment. RESULTS:
      Following treatment, only external motivation changed (decreased), whereas the
      other dimensions of motivation retained the high levels observed pretreatment.
      Depression (as measured by the Beck Depression Inventory, BDI) was highly
      correlated with three of the four domains of motivation, while anxiety (as
      measured by the Spielberger State-Trait Anxiety Inventory, STAI) was highly
      correlated solely with internal motivation. CONCLUSIONS: Our findings suggest
      that depression and anxiety may differentially effect motivation and that
      external motivation may be quite transient; treatment implications of these
      findings are discussed. The usefulness of the TMQ in a residential population was
      also explored.

PMID- 12507529
TI  - The influence of salivary activity in evaluating adolescent tobacco consumption
      by determining the level of thiocyanate in saliva.
AB  - The thiocyanate (SNC) concentration in saliva is a biochemical measure frequently
      used as an objective indicator of tobacco consumption. However, variations in the
      volume of saliva can influence SNC levels, making it more difficult to ascertain
      the relation between tobacco consumption and SNC concentration. The goal of this
      study was to determine the extent to which salivary activity can influence SNC
      concentration in saliva among adolescents. We measured the SNC concentration in
      saliva and the salivary activity (using cotton dental rolls) of 592 students aged
      14-17 years. The results of a stepwise regression analysis did not show any
      significant effect of the salivary activity on SCN levels.

PMID- 12507530
TI  - Burnout and alcohol problems among urban transit operators in San Francisco.
AB  - Although occupational burnout has been linked with numerous psychosomatic
      symptoms and mental health problems, few studies have examined the association
      between burnout and substance use. This study assessed the contribution of
      burnout (Emotional Exhaustion--Maslach Burnout Inventory) to the risk of alcohol
      dependence and alcohol-related harm among a sample of urban transit operators.
      The study population consisted of 993 current drinkers who participated in the
      1993-1995 San Francisco Muni Health and Safety Study. A series of multivariate
      logistic regression models were developed to analyze the association between
      burnout and risk of alcohol problems after adjustment for seniority,
      sociodemographic factors, and mean daily ounces of ethanol. The results indicate
      that burnout is associated with elevated risk of alcohol dependence (odds ratio
      [OR] = 1.03; 95% confidence interval [CI] = 1.01, 1.06). The association between
      burnout and alcohol-related harm, however, was attenuated. These findings suggest
      that transit operators with higher levels of burnout may be at increased risk for
      alcohol problems, particularly alcohol dependence. The temporal relationship
      between the development of burnout and the onset of alcohol problems among
      occupational cohorts warrants further investigation.

PMID- 12507531
TI  - Household smoking behavior and ETS exposure among children with asthma in low
      income, minority households.
AB  - Environmental tobacco smoke (ETS) exposure was measured among 242 children with
      asthma who live in homes where at least one person smokes. Subjects were
      identified through clinics, schools, community agencies, and hospitals serving
      low-income, medically underserved communities in Los Angeles. Parents were
      surveyed about smoking behaviors in the household, children's ETS exposure, and
      attitudes towards smoking and smoking behavior change. Validation measures
      included urine cotinine for the child with asthma and passive air nicotine
      monitors placed in the subjects' homes. Overall reported levels of household
      smoking and ETS exposure were low, with a significant amount of household smoking
      taking place outside rather than inside the home. Over 47% of the respondents
      reported absolute restrictions against smoking in the home, and these
      restrictions were associated with lower reported levels of smoking, ETS exposure,
      and air nicotine and urine cotinine concentrations.

PMID- 12507532
TI  - Ethnic differences in smoking withdrawal effects among adolescents.
AB  - Smoking withdrawal effect information was collected from 75 adolescents (54 males
      and 21 females) making a quit attempt during a school-based smoking cessation
      program. A strong need to smoke was the most common withdrawal effect (60%),
      followed by irritability (51%), and difficulty concentrating (41%). Most (61%)
      participants experienced two or more withdrawal effects during the quit attempt,
      and withdrawal effects were evident in those smoking less than daily. Significant
      ethnic differences were found, with African Americans reporting significantly
      fewer withdrawal effects than Caucasians. After controlling for smoking
      frequency, African Americans were still less likely to report irritability,
      difficulty concentrating, and restlessness. Participants who chose to use
      nicotine replacement during the quit attempt were more likely to report
      difficulty concentrating, restlessness, and feeling miserable.

PMID- 12507533
TI  - Social supporters and drug use enablers: a dilemma for women in recovery.
AB  - The social networks of substance-using women consist of people who provide
      constructive social support, individuals who enable their drug use, and those who
      do both. Women's success in recovery may be attenuated because some of the people
      who are most likely to provide them with social support after drug treatment
      previously enabled their drug use. This article examines the social support
      systems of women offenders (N = 100) who were mandated to four therapeutic
      communities in New York City. The women had an average of nine supporters (four
      males and five females). Although most of the women had partners who provided
      them with constructive social support, many of their partners also enabled their
      drug use. Some of the women indicated that their partners did not provide
      constructive support but were among their main enablers, while half of the women
      said that their partners actually encouraged them to stop using drugs. The
      majority of the women also received support from their parents, siblings, other
      kin, and friends. Some of these supporters also enabled their drug use while
      others encouraged them to stop using drugs and enter drug treatment.

PMID- 12507534
TI  - Qualitative analysis of high-risk drug and alcohol use situations among severely
      mentally ill substance abusers.
AB  - Situational factors have been found to influence relapse to alcohol and drug use
      in general samples of substance abusers. However, little research exists
      examining the influence of interpersonal and intrapersonal determinants in
      samples of individuals dually diagnosed with a severe mental illness (SMI) and a
      substance use disorder (SUD). This study assessed high-risk alcohol and drug use
      situations in dually diagnosed individuals using focus group methodology.
      Qualitative data analysis yielded 10 themes that encompassed 33 high-risk
      situations: Psychological symptoms, positive and negative affect, reminders of
      substance use, being around people who use drugs and alcohol, interpersonal
      conflict, offers of drugs or alcohol, experiencing loss, receiving money, loss of
      appetite, and being abstinent. These results suggest that individuals with an SMI
      and SUD experience a number of unique high-risk situations that differ from those
      reported by non-SMI substance abusers. This study provides the basis for future
      quantitative studies assessing the prevalence of these situations in
      representative samples of SMI alcohol and drug abusers. This information allows
      for the development of relapse assessment instruments and treatment strategies
      appropriate for this population.

PMID- 12507535
TI  - Stressful events, personality, and mood disturbance: gender differences in
      alcoholics and problem drinkers.
AB  - The present study examined relationships among stressful events, personality
      characteristics, and affective status in males and females of various alcohol
      drinking patterns. We examined a total of 154 participants from three distinct
      alcohol subgroups: alcohol dependent, problem drinker, and light social drinker.
      These subjects did not meet criteria for any concurrent nonalcohol comorbid
      psychiatric disorder. The study included an alcohol quantity-frequency interview
      and self-report questionnaires on stressful life events, depressive symptoms,
      trait anxiety, and personality characteristics. Results showed female alcoholics
      reported significantly greater depression, anxiety, and neuroticism compared to
      their male counterparts (and all other drinking groups). Female problem drinkers
      reported significantly greater depressive symptoms and health-related stressful
      events compared to male problem drinkers and the light drinkers. In contrast,
      male problem drinkers did not show elevations on these dimensions and more
      closely resembled light drinkers, of whom no gender differences were found. The
      findings support theories suggesting a "telescoping" of complications, health
      related stress, and mood dysfunction in women at a lower threshold level of
      alcohol consumption compared to their male counterparts.

PMID- 12507536
TI  - Characteristics of gambling and problematic gambling in the Norwegian context: a
      DSM-IV-based telephone interview study.
AB  - The gaming business has increased considerably during the past years, and there
      are also some indications that the prevalence of pathological gambling has also
      increased. As it is important to know the problem size and character, an
      epidemiological study was performed in a representative sample of the Norwegian
      population (N = 2014; response rate 47.8%). The proportion that never gambled was
      31.2%, and a majority (47.2%) gambled sometimes, while 21.0% gambled often. Men
      (25.5%) gambled more often than women (17.7%). Lotto was the most popular game
      with 76.0%, followed by football tip (10.8%), slot machines (5.1%), and lotteries
      (4.9%). For some types of plays, there was a discrepancy between rank for
      playing, and for problematic playing. Slot machines gave higher problematic
      playing rank. The mean prevalence of problematic gambling (pathological gambling
      plus at-risk gambling) was 0.60%, with higher prevalence for those younger and
      for men. Men 18-30 had a very high prevalence (2.83), compared to men over 30
      (0.28%) and females 18-30 (0.84) and over 30 (0.12%). The total problematic
      gambling frequency was 1.97% for 18-30 years, and 0.1% over 30. There are no
      problematic gamblers over 50 in the material. The DSM-IV with its only 10
      questions gives a conservative estimate of pathological gambling. There were
      significant correlations between degree of gambling and some established risk
      factors.

PMID- 12507537
TI  - Antimuscarinics and the overactive detrusor--which is the main mechanism of
      action?
AB  - Contraction of the bladder, voluntary or involuntary, involves stimulation of the
      muscarinic receptors on the detrusor by acetylcholine, released from activated
      cholinergic nerves. Antimuscarinics are the drugs of choice for treatment of
      detrusor overactivity and the overactive bladder (OAB) syndrome. However,
      antimuscarinics at clinically recommended doses have little effect on voiding
      contractions, and may act mainly during the bladder storage phase, during which
      there is normally no parasympathetic outflow from the spinal cord. Supporting
      this, antimuscarinics have been shown to reduce bladder tone during storage, and
      to increase cystometric bladder capacity. A basal release of acetylcholine from
      non-neuronal (urothelial) as well as neuronal sources has been demonstrated in
      isolated human detrusor muscle. It is suggested that this release, which is
      increased by stretching the muscle and in the aging bladder, contributes to
      detrusor overactivity and OAB by eventually increasing bladder afferent activity
      during storage.

PMID- 12507538
TI  - Can predictive models for prostate cancer patients derived in the United States
      of America be utilized in European patients? A validation study of the Partin
      tables.
AB  - OBJECTIVES: Prostate cancer patients in the US and Europe differ due to selection
      and treatment differences. Accuracy of predictive tools derived in the US might
      therefore suffer when applied to European patients. We tested the validity of the
      widely accepted Partin tables for their ability to predict pathologic stage in
      German patients. METHODS: Clinical and pathological characteristics were obtained
      from 1,298 consecutive men with clinically localized prostate cancer undergoing
      radical prostatectomy at the University Hospital Hamburg between January 1992 and
      February 2000. Receiver operating characteristic (ROC) curve analysis was
      performed to compare observed and predicted Partin rates for each pathologic
      stage. RESULTS: The rate for organ confinement was 56% in Hamburg patients
      compared to 48% in the Partin study. The rates of Hamburg patients for
      extracapsular extension without seminal vesicle or lymph node involvement were
      25%, for seminal vesicle without lymph node involvement 14% and for lymph node
      metastases 5%. The corresponding rates of the Partin study were 40, 7 and 5%,
      respectively. The accuracy of Partin table derived probability was high with an
      area under the ROC curve of 0.817 (95% CI, 0.757-0.876) for organ confinement and
      0.807 (95% CI, 0.781-0.833) for lymph node involvement. CONCLUSION: Our study
      demonstrated that predictive tools for prostate cancer developed in the US could
      be applied to European patients with comparable accuracy to that reported for
      validation studies performed with US patients.

PMID- 12507539
TI  - PSA progression following radical prostatectomy and radiation therapy: new
      standards in the new Millennium.
AB  - Prostate-specific antigen (PSA) progression following radical treatments of
      clinically localized prostate cancer is a common problem facing both the patient
      and the urologist. Not all patients with relapsing disease have an equal risk of
      death due to prostate cancer. After surgery, biochemical failure can be defined
      as persisting detectable levels of PSA after radical prostatectomy or a PSA rise
      after a period of normalization. On the other hand, definitions of PSA
      progression after radiation therapy vary and no clear consensus can be found.
      This review of the recent international literature updates the knowledge about
      the diagnostic procedures used in relapsing patients. Predictors of progression
      are precised leading to a better patient selection, based on currently available
      tables and nomograms. Indeed, identification of high risk patients may allow a
      more appropriate treatment decision. After radical treatment, the analysis of
      time to recurrence, PSA doubling time, PSA kinetics combined to modern imaging
      techniques such as 111In capromab penditide scan may allow a better
      identification of the recurrence site. Thus, an optimal treatment strategy may be
      envisaged such as local irradiation, salvage surgery, hormone therapy or
      combinations for which indications and results are provided. Alternative options
      such as cryotherapy still need further investigation. At last, the use of
      artificial neural networks will certainly enhance the selection of patients
      submitted to radical treatments as well as the selection of relapsing patients to
      allow a more appropriate adjuvant therapy.

PMID- 12507540
TI  - Prostate specific antigen doubling time as auxiliary end point in hormone
      refractory prostatic carcinoma.
AB  - OBJECTIVE: In hormone refractory prostatic carcinoma (HRPCa), the majority of
      patients have bone metastases only, which are by definition non-measurable. This
      makes objective evaluation of chemotherapeutic agents difficult. Prostate
      specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end
      point in HRPCa. METHODS: In the framework of a master protocol, the Swiss Group
      for Clinical Cancer Research (SAKK) is evaluating cytotoxic drugs in HRPCa since
      1991. These prospective phase II trials include uniform requirements with regard
      to response, toxicity and quality of life. From the entire pool of patients, 40
      with bidimensionally measurable metastases (lymph nodes, visceral organs) could
      be identified. PSA doubling time was calculated in patients with a rising PSA
      during therapy. RESULTS: Objective best response to any given chemotherapeutic
      agent was: partial remission (PR) in six patients (15%), stable disease (SD) in
      13 (32%) and progressive disease (PD) in 21 (53%). PSA remained stable or
      decreased in four of six patients with PR (67%), seven of 13 with SD (54%) but
      only in four of 21 with PD (19%) (Cochran-Armitage test for trend; p=0.015). The
      median PSA doubling time for patients with a rising PSA was 238 days in PR and
      224 days in SD, compared to 113 days in PD (Wilcoxon test; p=0.002). CONCLUSIONS:
      PSA doubling time is a potential auxiliary end point in the evaluation of
      cytotoxic drugs in HRPCa. Thus, also patients with non-measurable (bone)
      metastases could be included in analysis of response.

PMID- 12507541
TI  - Tissue polypeptide-specific antigen (TPS) determinations before and during
      intermittent maximal androgen blockade in patients with metastatic prostatic
      carcinoma.
AB  - OBJECTIVE: To evaluate the prognostic significance of serially measured tissue
      polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic
      carcinoma treated with intermittent maximal androgen blockade (MAB). To determine
      its value with respect to predicting response to treatment and time to clinical
      progression. Finally to compare TPS with prostate-specific antigen (PSA)
      measurements in terms of prognostic impact in patients with metastatic prostatic
      carcinoma. METHODS AND PATIENTS: TPS and PSA measurements were performed before
      start of and monthly during intermittent MAB in 68 patients participating in
      EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients
      from eight centers were included in the final analysis because at least three TPS
      values were available. TPS and PSA values were correlated with clinical course of
      the disease. Median follow-up was 21.3 months. Three patient groups were defined
      on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically
      stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA
      value following 9 months of treatment (n=5). RESULTS: Pretreatment TPS was
      significantly higher in the clinically progressive patients than in the other
      patient groups (p=0.0041). When grouping patients according to their pretreatment
      TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l)
      proved to be a statistically significant prognostic factor with respect to time
      to progression: elevated TPS was associated with a 3.8 increased risk for
      progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no
      prognostic value for time to progression. In five patients increase of TPS
      coincided with or preceded clinical progression during treatment, whereas PSA
      remained normal. CONCLUSION: Additional value of pretreatment TPS measurements in
      metastatic prostate cancer patients is found in defining the patients with rapid
      clinical progression. Following MAB an increase in TPS signifies clinical
      progression even if PSA is found to remain normal.

PMID- 12507542
TI  - Prognostic significance of tumor volume after radical prostatectomy: a
      multivariate analysis of pathological prognostic factors.
AB  - OBJECTIVES: To analyze the association between Gleason score, stage and status of
      surgical margins with tumor volume in prostate cancer progression after radical
      prostatectomy. METHODS: 200 consecutive radical prostatectomy specimens were
      analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well
      as pathological results were noted. A biochemical recurrence was defined as a
      single, postoperative detectable PSA level (>0.2 ng/ml). Tumor volume was
      compared to postoperative staging, Gleason score, and surgical margin status to
      predict tumor progression. Univariate and multivariate analysis using stepwise
      logistic regression were used to identify parameters with additional prognostic
      value. RESULTS: Pathological results of the prostatectomy specimens showed 149
      (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57
      cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively
      (p<0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc,
      respectively (p<0.0001). Five-year progression-free actuarial survival was 69.7%.
      Using univariate analysis, tumor progression correlated with final Gleason score
      (p<0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage
      (p<0.0001). In a multivariate analysis, tumor progression correlated only with
      the final Gleason score (p=0.04) and stage (p=0.0002). CONCLUSION: Gleason score
      and pathological stage are independent factors to predict prostate cancer
      progression after radical prostatectomy. When these parameters are known, tumor
      volume does not provide additional information.

PMID- 12507543
TI  - Thymidine phosphorylase and dihydropyrimidine dehydrogenase in renal cell
      carcinoma: relationship between histological parameters and chemosensitivity to 5
      fluorouracil.
AB  - OBJECTIVES: Thymidine phosphorylase (TdR-Pase) and dihydropyrimidine
      dehydrogenase (DPD) are thought to be key enzymes in the metabolic pathway of 5
      fluorouracil (5-FU). Theoretically, cancer cells which have high TdR-Pase
      activity and/or low DPD activity should be sensitive to 5-FU. TdR-Pase is also
      known to have angiogenic activity which helps tumor progression and metastasis.
      On the other hand, little is known concerning the relationship of DPD activity
      with clinical malignant potential in renal cell carcinoma (RCC). In this study,
      we measured both TdR-Pase and DPD activities in surgically obtained RCC tissues
      and examined the relationship between these enzymatic activities and histological
      parameters. In addition, the results of in vitro chemosensitivity testing were
      also analyzed to determine whether TdR-Pase and/or DPD activity in carcinoma
      cells can predict the efficacy of 5-FU. METHODS: RCC tissues from 53 patients
      were obtained. TdR-Pase and DPD activities were measured by ELISA and radioenzyme
      assay, respectively. Sensitivity to 5-FU was assessed by histoculture drug
      response assay (HDRA), an in vitro chemosensitivity test, for 20 of the 53
      specimens. RESULTS: Both TdR-Pase and DPD activities of RCC increased with
      histological grade. There was a significant positive correlation between the TdR
      Pase activity and 5-FU sensitivity. In addition, a stronger positive correlation
      was found between TdR-Pase / DPD ratio and 5-FU sensitivity. DPD exhibited no
      correlation with 5-FU sensitivity. CONCLUSIONS: The activity of both enzymes
      increased with malignant potential of RCC. TdR-Pase appeared to be the enzyme
      regulating activation of 5-FU in RCC.

PMID- 12507544
TI  - Gender-related differences in clinical and pathological characteristics and
      therapy of bladder cancer.
AB  - OBJECTIVE: To confirm the very high male:female ratios previously observed among
      Spanish bladder cancer patients and to assess gender differences in tumoral
      characteristics, diagnostic procedures, and treatment in a large series of
      consecutive bladder cancer patients. PATIENTS AND METHODS: All newly diagnosed
      bladder cancer patients (n=615) in 17 Spanish hospitals, between 1997-2000, were
      included. Information was collected both through personal interviews to patients
      and from medical records using a structured form. RESULTS: Seventy-six percent of
      tumours were superficial. The male:female ratio was 6.7 and it was similar for
      superficial and infiltrating tumours. Women were older than men at the diagnosis
      of bladder cancer (68.2+/-9.4 years versus 65.7+/-9.7 years, p=0.01). Ten percent
      of superficial tumours in women, versus 3% in men, were classified as "other
      histological types" (p=0.008). T1GIII tumours were more frequent among men (17%
      versus 7%, p=0.047). On the other hand, women were more likely to present with 0a
      stage tumours (48.6% versus 35.5%, p=0.04), multiple tumours (50% versus 29%,
      trend test: 0.005), multi-centric tumours (54% versus 38%, p=0.019), and larger
      infiltrating masses (5.2 cm versus 3.8 cm, p=0.03) than men. Among 0a-stage
      tumours, only 23% of women compared to 54% of men received transurethral
      resection (TUR) alone (p=0.002). Women were almost five-fold more likely to
      receive additional therapies to TUR (p=0.004) after adjusting for age,
      geographical area, stage, tumoral size, nuclear grade, and multiplicity.
      CONCLUSION: The study confirms the very high male:female ratio of bladder cancer
      in Spain. We found substantial differences in the pathological characteristics of
      tumours from men and women. There was a tendency for women to receive more
      frequently non-standard, more aggressive, therapy than men.

PMID- 12507545
TI  - Are urodynamic tests useful tools for the initial conservative management of non
      neurogenic urinary incontinence? A review of the literature.
AB  - OBJECTIVES: To summarise the evidence for the role of urodynamic tests in the
      diagnosis and classification of urinary incontinence. METHODS: Reference lists in
      relevant papers were reviewed and MEDLINE searches conducted. RESULTS: The mean
      sensitivity (specificity) of clinical history versus urodynamic tests was 0.82
      (0.57) for stress incontinence, 0.69 (0.60) for urge incontinence/overactive
      bladder, and 0.51 (0.66) for patients with mixed incontinence. The proportion of
      women with a clinical diagnosis of urinary incontinence but with normal findings
      from urodynamic tests ranged from 3 to 8%. Overall sensitivity of urodynamic
      tests was about 85-90% in the diagnosis of urodynamic stress incontinence, but
      generally lower following diagnosis of urge and mixed incontinence. No
      relationship emerged between urodynamic test results and response to medical
      treatment. CONCLUSIONS: This literature review shows that the sensitivity of
      clinical history versus urodynamic tests was 0.82, 0.69 and 0.51 respectively for
      stress, urge and mixed urinary incontinence. It also suggests that urodynamic
      diagnosis does not predict response to treatment. These data add to the ongoing
      'urodynamics or no urodynamics' debate in the evaluation of urinary incontinence
      and show that urodynamic testing may not be helpful for patients receiving
      initial non-invasive therapy. These data are in line with the conclusions of the
      1st and 2nd International Consultations on incontinence.

PMID- 12507546
TI  - New percutaneous technique of sacral nerve stimulation has high initial success
      rate: preliminary results.
AB  - OBJECTIVE: We report on the new technique of sacral nerve stimulation in the
      treatment of voiding dysfunction. This new technique is characterized by
      percutaneous approach to the sacral nerves resulting in minimally invasiveness of
      the procedure and the ability to have patient awake during the electrode
      placement. METHODS: Since December 1999, we prospectively evaluated patients who
      underwent this novel percutaneous technique approach. Thirty-two patients (10
      male, 22 female, mean age 43 years) were included and no complications were
      reported. Average follow-up time was 11 months (range 2-25 months). Main elements
      of the new technique are also described. The needle is inserted into the sacral
      foramen to a desired location (usually S3) and metal stylet is then inserted
      through the needle. With metal stylet only in the foramen, two dilators are
      successively inserted and the chronic lead is placed through the plastic dilator.
      Only a very small skin incision is necessary to allow the anchor fixation.
      RESULTS: Out of the 32 patients who underwent the percutaneous lead placement, 22
      received the neurostimulator (IPG). Out of the remaining 10 patients, 4 are still
      in screening and 6 had unsuccessful results (<50% improvement) and therefore did
      not undergo the second stage (neurostimulator placement). From the 22 implanted
      patients, 20 reported 90% improvement in their primary voiding symptoms, 1 had an
      improvement between 50 and 70% and 1 patient was explanted due to IPG damage
      following magnetic resonance imaging. There were total of four lead
      displacements, two occurred where the silicone anchoring was used and the other
      two occurred when no anchoring was done. CONCLUSION: Success rate of this
      technique in selecting patients for the permanent implant is significantly higher
      than currently reported in the literature. Very beneficial clinical outcome of
      the implanted patients confirms better patient selection with no complications.
      Our experience with this technique shows the feasibility of percutaneous lead
      placement with major advantages such as: (1) use of local anesthesia and
      possibility to test sensitive responses during implant, (2) the possibility for
      more accurate patient selection by using the definitive lead for a longer test
      period before proceeding with the neurostimulator (IPG) implant. The presented
      percutaneous technique requiring fascial lead fixation represents a safe and
      effective method of Sacral Neuromodulation Therapy.

PMID- 12507547
TI  - Stone treatment and coagulopathy.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate treatment
      protocols and results of upper tract stone treatment in patients with clotting
      disorders. METHODS: In a 6-year period, 6,827 stone interventions (ESWL or
      endourologic procedures) were performed in 5,739 patients. Thirty-five (0.61%)
      patients suffered from a variety of systemic clotting disorders or were anti
      coagulated. Clotting disorders were corrected by specific therapy prior to any
      intervention. A total of 76 interventions were performed consisting of ESWL,
      ureteroscopy (URS), percutaneous nephrolithotomy (PNL), ureteric stenting or
      percutaneous nephrostomy. RESULTS: All patients became stone-free within 3 months
      or had clinically insignificant residual fragments. Severe complications were
      observed in 10/76 (13.1%) interventions. ESWL was successful in 88.9% (16/18) of
      patients, but associated with a 33.3% (6/18) complication rate; 27.8% (5/18) of
      patients required auxiliary procedures. URS and PNL were successful in all cases
      and complications occurred in 0% (0/7) and 33% (1/3) of patients, respectively.
      Time to complete stone clearance after ESWL was 32.0+/-49.3 days compared with a
      mean of 19.4+/-28.6 days in a non-coagulopathy control group; no difference was
      observed for endourologic procedures. Average costs of treatment in patients
      undergoing ureteroscopy was higher in patients with coagulopathy (4,611 versus
      2,342); however, the difference was less pronounced compared with ESWL (6,070
      versus 1,731). CONCLUSION: Patients with coagulopathy have a higher rate of
      complications despite apparently normal clotting parameters during treatment and
      hospitalisation was prolonged. The efficacy of ESWL was lower in patients with
      coagulopathy and we currently favour endoscopic procedures for stone removal in
      this patient group.

PMID- 12507548
TI  - Vesicoureteral reflux detected among patients with nocturnal enuresis.
AB  - OBJECTIVES: To clarify the characteristics of vesicoureteral reflux detected in
      patients with nocturnal enuresis. METHODS: Voiding cystourethrography (VCUG) was
      applied in 1,088 patients who visited our outpatient clinic with the chief
      complaint of nocturnal enuresis. The clinical features of reflux were evaluated
      and the prognosis of reflux and nocturnal enuresis was analyzed. RESULTS: Reflux
      was detected in 86 ureters in 70 patients (6.4%) out of the 1,088 patients. The
      grade of reflux was 3 or less in all cases. The incidence of pyuria was 5 (7%)
      and that of renal scar during first examination was 1 (1%). The incidence of
      unstable bladder was 30 (75%) in 40 patients. The resolution rate of reflux in
      the cases which were followed-up for 2 years or more by conservative treatment
      was 50-66% for each grade of reflux. The percentage of patients who had siblings
      with a positive history of nocturnal enuresis and the incidence of frequency
      differed significantly between the enuretics with reflux and the 507 enuretics
      without urological abnormalities. CONCLUSIONS: Our data suggest that the
      incidence of reflux in patients with nocturnal enuresis was rather low in
      comparison with the past literature, the severity was mild and the resolution
      rate by conservative treatment was rather high.

PMID- 12507549
TI  - The changes in testicular vascular permeability during progression of the
      experimental varicocele.
AB  - OBJECTIVES: The vascular permeability of testicular capillaries which play a role
      in controlling the formation of testicular interstitial fluid was studied during
      the progressive course of experimental varicocele. MATERIALS AND METHODS: The
      pathology was developed through partial ligation of left renal vein in four
      groups of rats. Controls of each group were subjected to sham surgery. After
      different periods of varicocele creation (1, 3, 6 and 14 weeks), animals' testes
      per one of the study groups were extirpated and weighed. The volume density
      percentages of polymorphnuclear leukocytes (PMN) per testicular blood vessels;
      which are markers of the increase in vascular permeability, were also estimated
      in both testes. To further verify the obtained findings, another group of animals
      received human chorionic gonadotrophin (hCG) treatment 6 weeks after varicocele
      creation and their histopathological sections were examined. RESULTS: Animal
      testes' of (1 and 3 weeks) groups were found to be significantly heavier (p<0.05)
      than their controls. PMN showed accumulation in testicular blood vessels and
      their volume density percentages per these blood vessels in both testes were
      significantly higher in each study group than in those of its controls. However,
      these percentages showed gradual significant decline as the duration of
      varicocele bearing gradually increased. The hCG-treated animals revealed more
      accumulation of the PMN in their histopathological sections. CONCLUSION: The
      present results suggest that experimental varicocele may induce an increase in
      testicular vascular permeability, which then decreases gradually with time. It is
      supposed that parallel changes in the rate of formation of testicular
      interstitial fluid may be accompanied. The results have also showed that the
      vasculature of the testis with experimental varicocele can still respond to hCG.

PMID- 12507552
TI  - RING finger ubiquitin protein ligases: implications for tumorigenesis, metastasis
      and for molecular targets in cancer.
AB  - Covalent modification of proteins with ubiquitin regulates almost all aspects of
      eukaryotic cellular function. Ubiquitin protein ligases (E3s) play central
      regulatory roles in that they provide substrate specificity to this process and
      therefore, represent attractive molecular targets for disease therapy. We
      summarize recent advances in our understanding of RING finger and RING finger
      related E3s with emphasis on BRCA1 and the tumor autocrine motility factor
      receptor (gp78), as well as discuss the potential for components of the ubiquitin
      pathway for proteasomal degradation as molecular targets.

PMID- 12507553
TI  - NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome
      based therapeutic approach.
AB  - Nuclear factor-kappa B (NF-kappaB) activation relies primarily on ubiquitin
      mediated degradation of its inhibitor IkappaB. NF-kappaB plays an important role
      in many aspects of tumor development, progression, and therapy. Some types of
      cancer are characterized by constitutive NF-kappaB activity, whereas in others
      such activity is induced following chemotherapy. NF-kappaB-harboring tumors are
      generally resistant to chemotherapy and their eradication requires NF-kappaB
      inhibition. Here we describe the mechanisms of NF-kappaB activation in normal and
      tumor cells, review prevalent notions regarding the factor's contribution to
      tumorigenicity and discuss present and future options for NF-kappaB inhibition in
      cancer. The ubiquitination-mediated activation of NF-kappaB is intersected by
      another cancer-associated protein, beta-catenin. We, therefore, compare the
      related activation pathways and discuss the possibility of differential targeting
      of the involved ubiquitination machinery.

PMID- 12507554
TI  - The role of ubiquitylation in signaling by growth factors: implications to
      cancer.
AB  - Cancer cells depend on multiple, locally produced growth factors. Signaling by
      growth factors entails phosphorylation events, and its termination is determined
      primarily by endocytosis of growth factor receptor complexes. One group of growth
      factor receptors frequently implicated in human cancer is the ErbB family of
      receptor tyrosine kinases. By using ErbB as a prototype, here we review the role
      of protein ubiquitylation in the process that terminates signaling. Specifically,
      we concentrate on several adaptor proteins, including c-Cbl and Hgs, to elucidate
      the complexity of receptor sorting for degradation. Detailed understanding of
      ubiquitylation control on receptor desensitization may lead to better ways to
      diagnose and eradicate cancer.

PMID- 12507555
TI  - Deregulated degradation of the cdk inhibitor p27 and malignant transformation.
AB  - p27 acts as a critical negative regulator of the cell cycle by inhibiting the
      activity of cyclin/cdk complexes during G0 and G1. Degradation of p27 is a
      critical event for the G1/S transition and occurs through ubiquitination by
      SCF(Skp2) and subsequent degradation by the 26S-proteasome. A tumor suppressing
      function of p27 has been demonstrated in mouse models and studies of human
      tumors. More recent evidence suggests that Skp2, the specific recognition factor
      for p27 ubiquitination, has oncogenic properties. This review will focus on the
      regulation of p27 proteolysis and its consequences for tumorigenesis.

PMID- 12507556
TI  - The p53-Mdm2 module and the ubiquitin system.
AB  - The p53 tumor suppressor protein is a short-lived protein, which is stabilized in
      response to cellular stress. The ubiquitination and degradation of p53 are
      largely controlled by Mdm2, an oncogenic E3 ligase. Stress signals lead to p53
      stabilization either by induction of covalent modifications in Mdm2 and p53, or
      through altered protein-protein interactions. Mdm2 also harbors a post
      ubiquitination function, probably enabling efficient targeting of ubiquitinated
      p53 to the proteasome. p53 ubiquitination is associated with its export from the
      nucleus into the cytoplasm. However, the exact site of degradation of p53 is
      presently under debate. p53 may be targeted by other E3 ligases besides Mdm2, as
      well as by non-proteasomal mechanisms. Despite extensive information about p53
      degradation, many important aspects remain unresolved.

PMID- 12507557
TI  - Human papillomavirus-induced carcinogenesis and the ubiquitin-proteasome system.
AB  - Certain types of human papillomaviruses have been etiologically associated with
      malignant lesions, most notably with cervical cancer. The major oncoproteins of
      these cancer-associated viruses are encoded by the viral E6 and E7 genes.
      Thorough characterization of these oncoproteins and their interaction with
      cellular proteins has shown that both E6 and E7 exploit the ubiquitin-proteasome
      system to degrade and, thus, to functionally inactivate negative cell-regulatory
      proteins including members of the p110(RB) family and p53. This act of piracy is
      assumed to contribute to both the efficient propagation of HPVs and HPV-induced
      carcinogenesis.

PMID- 12507558
TI  - The ubiquitin/proteasome system in Epstein-Barr virus latency and associated
      malignancies.
AB  - Epstein-Barr virus (EBV) is a human herpesvirus associated with lymphoid and
      epithelial malignancies. Three viral proteins, the EBV nuclear antigen 1 and the
      latent membrane proteins-1 and -2A, regulate viral latency by manipulating
      ubiquitin-dependent proteolysis. The activation of cellular oncogenes is
      instrumental for the progression of EBV infected cells to full malignancy.
      Constitutively activation of c-myc correlates with decreased proteasomal activity
      and upregulation of compensatory proteolytic pathways in Burkitt's lymphomas.
      Knowledge of these multiple strategies of interference with regulated proteolysis
      may provide new clues for the treatment of EBV-associated malignancies.

PMID- 12507559
TI  - Regulation of the Fanconi anemia pathway by monoubiquitination.
AB  - Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome
      characterized by multiple congenital anomalies, bone marrow failure, and cellular
      sensitivity to mitomycin C (MMC). To date, six FA genes have been cloned, and the
      encoded proteins function in a novel pathway. The FA pathway is required for the
      normal cellular response to DNA damage. Following DNA damage, the pathway is
      activated, leading to monoubiquitination of the FA protein, FANCD2, and its
      targeting to subnuclear foci. Disruption of the FA pathway results in the absence
      of FANCD2 nuclear foci, leading to the cellular and clinical abnormalities of FA.
      Here, we review the recent studies describing the regulated monoubiquitination of
      the FANCD2 protein and discuss the interaction of the FA pathway with other DNA
      damage response pathways.

PMID- 12507560
TI  - The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1)
      degradation, and cancer pathogenesis.
AB  - Recently, work on the mechanism of action of the von Hippel-Lindau tumour
      suppressor protein (pVHL) and studies on hypoxic gene regulation have converged,
      providing insights into both cellular oxygen sensing and cancer pathogenesis.
      pVHL is the recognition component of the E3-ubiquitin ligase complex involved in
      the degradation of hypoxia-inducible factor-1 (HIF) alpha-subunits, a process
      regulated by oxygen availability and blocked by disease causing pVHL mutations.
      In normoxic cells, pVHL targeting of HIF-alpha subunits follows hydroxylation of
      critical HIF prolyl residues by a group of oxygen, 2-oxoglutarate- and iron
      dependent enzymes. In this review, we outline current understanding of
      HIF/pVHL/prolyl hydroxylase pathway and consider the implications for VHL
      associated cancer.

PMID- 12507561
TI  - The transmission of Mycobacterium bovis infection to cattle.
AB  - The prevalence of Mycobacterium bovis infection in cattle is increasing rapidly
      in some countries, including the UK and Ireland. The organism infects a wide
      range of mammalian hosts, and eradication of the disease is difficult if there is
      an extensive reservoir in the wildlife population. Existing evidence suggests
      that wildlife vectors include the European badger in the UK and Ireland, the
      brush-tailed possum and ferret in New Zealand and ungulates in some other
      countries. Cattle grazing field boundaries or short swards are at particularly
      high risk, since the chance of contact with the intermediate host or their
      excreta is increased. There is evidence that the transmission of the disease
      between cattle following movement accounts for 10-15% of outbreaks in the British
      Isles and that transmission can occur across farm boundaries. The prevalence the
      prevalence of single reactors in herds suggested that within-herd transmission
      was not common. In herds with infected cattle, spreading slurry is a risk factor,
      which can be minimised by prolonged storage of the slurry, by spreading it on
      fields not used for grazing or by soil injection. M. bovis also survives in water
      and may enter the respiratory tract during drinking. It is concluded that M.
      bovis infection in cattle can be transmitted by a number of routes, some of which
      can be controlled by appropriate husbandry, but that circumstantial evidence
      suggests that the existence of a widespread intermediate host is the greatest
      contributor to infection in cattle.

PMID- 12507562
TI  - Efficacy of calfhood vaccination with Brucella abortus strain RB51 in protecting
      bison against brucellosis.
AB  - In the studies reported here, protection induced by calfhood vaccination of bison
      with 1.2-6.1 x 10(10)CFU of Brucella abortus strain RB51 (SRB51) against a
      virulent strain of B. abortus was evaluated. Non-vaccinated and SRB51-vaccinated
      bison were intraconjunctivally challenged during midgestation with 3 x 10(7)CFU
      of virulent B. abortus strain 2308 (S2308). Maternal and fetal tissues were
      obtained within 24hour after abortion or parturition. Incidence of abortion was
      greater (P<0.05) in non-vaccinated as compared to SRB51-vaccinated bison (62% and
      15%, respectively), with abortions occurring between 5 and 8 weeks after
      experimental challenge. Calves from bison vaccinated with SRB51 had a reduced
      (P<0.05) prevalence of fetal infection with S2308 as compared to calves from non
      vaccinated bison (19% and 62%, respectively). Although the ability to recover the
      2308 challenge strain from maternal tissues did not differ (P>0.05) between
      nonvaccinates and vaccinates (100% and 78%, respectively), calfhood vaccination
      with SRB51 reduced (P<0.05) recovery of S2308 from uterine or mammary gland
      tissues. In bison which did not abort, S2308 was routinely recovered in low
      numbers from maternal lymphatic tissues; particularly the parotid, bronchial,
      supramammary, and mandibular lymph nodes. The RB51 vaccine strain was not
      recovered at any time from maternal or fetal samples obtained at necropsy.
      Histological lesions associated with Brucella-induced abortions were suppurative
      placentitis, fetal broncho-interstitial pneumonia, and fetal histiocytic
      splenitis. The results of our studies suggest that calfhood vaccination of bison
      with SRB51 is efficacious in protecting against intramammary, intrauterine, and
      fetal infection following exposure to a virulent strain of B. abortus during
      pregnancy. As brucellosis is transmitted horizontally through fluids associated
      with the birth or abortion of an infected fetus, or vertically to the calf
      through the ingestion of milk containing B. abortus, our data suggest that
      calfhood vaccination with SRB51 will be beneficial in preventing transmission of
      brucellosis in bison.

PMID- 12507563
TI  - Influences of naturally occurring and experimentally induced porcine pneumonia on
      blood parameters.
AB  - It had been the objective of the studies described to establish local and
      systemic changes by naturally occurring pneumonia or pneumonia experimentally
      induced by Pasteurella multocida and Haemophilus parasuis in swine. Acute and
      chronic pneumonia was found to alter the cytokine level of lung lavage fluid and
      affect the composition and function of blood cells, especially with regard to
      phagocytosis, radical formation and cell surface receptors. Interleukin-6 levels
      in blood plasma rose 24h after experimental intrabronchial infection. The
      influences of the changes on growth and meat quality are discussed.

PMID- 12507564
TI  - Cytokines in mammary lymph and milk during endotoxin-induced bovine mastitis.
AB  - Cytokine kinetics were examined in milk and in afferent and efferent lymph of the
      supramammary lymph node after intramammary infusion of endotoxin from Escherichia
      coli. Cows were sampled 0, 2 and 4h after infusion (p.i.). Neutrophils appeared
      in afferent lymph 2h p.i., and in efferent lymph and milk 4h p.i. The milk
      contained high concentrations of interleukin-8 (IL-8) at 2 and 4h p.i. IL-8 was
      also found in lymph, but at lower concentrations. The tumor necrosis factor-alpha
      (TNF-alpha) concentration tended to increase in afferent lymph at 2h p.i., and
      increased in milk at 4h p.i. The level of IL-1beta increased at 4h p.i. in milk,
      but was not detected in lymph. Interferon-gamma was not detected in any sample,
      at any time. The results indicate a primary role for IL-8 in the recruitment of
      neutrophils into the gland, and suggest that IL-1beta and TNF-alpha are not
      necessary for IL-8 production and release in response to endotoxin.

PMID- 12507565
TI  - Evaluation of a commercially available enzyme-linked immunosorbent assay for the
      detection of allergen-specific IgE antibodies in dogs.
AB  - Twenty-eight atopic dogs, 22 pruritic, non-atopic dogs and 10 healthy dogs were
      ELISA tested. For calculations of diagnostic specificity and sensitivity,
      positive ELISA test results in non-atopic dogs were considered false positive
      results. The absence of any positive results in the atopic dogs was considered
      false negative results. The atopic dogs were tested both with ELISA and an
      intradermal test, utilising allergen extracts from the same manufacturer, to
      determine the frequency of positive allergen reactions in the ELISA test compared
      with the intradermal test. The Prausnitz-Kustner test was performed to evaluate
      the significance of a positive ELISA test result. Based on cross-tabulations with
      clinically defined atopic dermatitis, the ELISA test showed a sensitivity of
      53.6% and a specificity of 84.4%. The correlation between the ELISA and the
      intradermal test was poor. Positive Prausnitz-Kustner tests were not obtained
      using sera from dogs that were intradermal test negative for the tested
      allergens, even though sera had high levels of IgE as measured by the ELISA.
      These findings question the significance of a positive ELISA test result and
      indicate that the test is not measuring functional allergen-specific IgE.

PMID- 12507566
TI  - Trypanosome-induced modulation of responses to concurrent helminth infection.
AB  - Infections with African trypanosomes are known to suppress immune responses to
      vaccines and to gastrointestinal nematode infections in livestock. Experimental
      infections with Trypanosoma brucei (Tb) and the gastrointestinal nematode
      Nippostrongylus brasiliensis (Nb) in mice were used to identify possible
      mechanisms involved in interference with anti-worm responses and to examine the
      effects of host genotype on the extent of suppression seen. Concurrent infections
      with T. brucei resulted in a prolongation of worm survival and a dramatic
      increase in faecal egg output. Infection also resulted in a marked suppression of
      the proliferative response of mesenteric lymphocytes (MLNC) to in vitro mitogenic
      stimulation. When MLNC from concurrently infected mice were stimulated in vitro
      with the mitogen ConA they released more IFN-gamma and less IL-5 than cells from
      mice infected only with N. brasiliensis. These data are interpreted in terms of a
      trypanosome-mediated influence on the development of host-protective type-2 T
      helper cell responses against N. brasiliensis. The degree to which T. brucei
      altered the kinetics of the nematode infection was influenced by the particular
      mouse strain concerned.

PMID- 12507567
TI  - An experimental infection model for reproduction of calf pneumonia with bovine
      respiratory syncytial virus (BRSV) based on one combined exposure of calves.
AB  - Bovine respiratory syncytial virus (BRSV) has been recognised as an important
      pathogen in calf pneumonia for 30 years, but surprisingly few effective infection
      models for studies of the immune response and the pathogenesis in the natural
      host have been established. We present a reproducible experimental infection
      model for BRSV in 2-5-month-old, conventionally reared Jersey calves. Thirty-four
      colostrum-fed calves were inoculated once by aerosol and intratracheal injection
      with BRSV. Respiratory disease was recorded in 91% of the BRSV-inoculated calves,
      72% had an accompanying rise in rectal temperature and 83% exhibited >5%
      consolidation of the lung tissue. The disease closely resembled natural outbreaks
      of BRSV-related pneumonia, and detection of BRSV in nasal secretions and lung
      tissues confirmed the primary role of BRSV. Nine mock-inoculated control calves
      failed to develop respiratory disease. This model is a valuable tool for the
      study of the pathogenesis of BRSV and for vaccine efficacy studies.

PMID- 12507568
TI  - Tissue chamber model of acute inflammation in farm animal species.
AB  - A tissue chamber model of acute inflammation for use in comparative studies in
      calves, sheep, goats and pigs has been established and validated. Tissue chambers
      were prepared from silicon rubber tubing, of inner diameter 12.7 mm, length 115
      mm and volume 15 ml, with 10 holes, each of 6mm diameter, at each end. In each
      animal two or four chambers were inserted at subcutaneous sites. Six weeks after
      implantation an acute inflammatory reaction in a single cage was generated by the
      intracaveal injection of 0.5 ml of 1% carrageenan solution. Serial samples of
      exudate (injected chamber), transudate (non-injected chamber) and blood were
      collected for measurement of exudate and transudate leucocyte count,
      prostaglandin (PG)E(2) concentration in exudate and serum thromboxane (Tx)B(2)
      concentration. In addition, skin temperature changes over exudate and transudate
      chambers were recorded. In all four species, carrageenan induced an acute
      inflammatory response, indicated by increases to peak values followed by return
      towards baseline in skin temperature, leucocyte count and PGE(2) concentration.
      For each of these variables in calves, sheep and goats the increases were
      significantly greater for exudate than for transudate. The degree of intra
      species variation in each variable was acceptable. Marked inter-species
      differences were recorded: skin temperature rise was greatest in calves and least
      in sheep and goats; exudate PGE(2) concentration was increased in the order
      sheep>goat>pig>calf; serum TxB(2) concentration was increased in the order
      calf>goat>sheep>pig and exudate leucocyte count was increased to a greater extent
      in the pig than in the three ruminant species. The model has advantages over some
      previously described tissue chamber models of inflammation and will be suitable
      for use in comparative studies of inflammatory mechanisms and the
      pharmacokinetics and pharmacodynamics of anti-inflammatory drugs.

PMID- 12507569
TI  - Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and
      intramuscular administration to horses.
AB  - The pharmacokinetic properties of norfloxacin-glycine acetate (NFLXGA) were
      determined in six horses following a single intravenous (i.v.) and intramuscular
      (i.m.) dose of 4 mgkg(-1) body weight. Following i.v. and i.m. administration,
      the plasma drug concentrations were best fitted by an open two-compartment model
      with a rapid distribution phase. After i.v. NFLXGA administration, the
      distribution (t(1/2alpha)) and elimination half-life (t(1/2beta)) were 0.42
      (0.05) and 5.44 (1.36)h. The volume of distribution of NFLXGA at steady state
      (Vd(ss)) was 2.19 (0.53) Lkg(-1). After NFLXGA i.m. administration, the maximal
      absorption concentration (C(max)) was 0.44 (0.04) microgml(-1) at 0.86 (0.15)h
      (T(max)). The mean absorption (t(1/2ka)) and elimination half-life (t(1/2beta))
      of NFLXGA were 0.27 (0.07) and 9.47 (2.24)h, respectively. The mean systemic
      bioavailability (F) following i.m. administration was 55 (12)%. The optimal
      dosage for each administration route was calculated from the pharmacokinetic data
      on the basis of the area under the inhibitory plasma concentration-time curve
      (AUIC) every 24h and was found to be 13.36 and 7.35 mgkg(-1) for i.m. and i.v.
      administration, respectively.

PMID- 12507570
TI  - The gross and radiographic appearance of sacroiliac ankylosis capsularis ossea in
      the dog.
AB  - This study was carried out to determine the incidence and to describe the
      radiographic appearance of ankylosis capsularis ossea at the canine sacroiliac
      joint, as well as to determine factors, which might cause radiographic
      misinterpretation of this finding. Bone specimens of 646 pelves of pure-bred dogs
      were assessed for morphological evidence of ankylosis capsularis ossea. The
      lesion was most commonly present at the cranioventral aspects of the sacroiliac
      joint. More than 50% of adult dogs had signs of being at least mildly affected.
      Among these, large and giant breeds were most commonly involved. Unlike moderate
      and severe degrees of this disease, smaller osteophytes had not been visualised
      on radiographs. For radiographic diagnosis, angled views of the sacrum are
      recommended. In central views of the sacrum, the presence of increased sacral
      concavity consistent with increased ilial convexity of the caudal aspect of the
      sacroiliac contact area might simulate the presence of ankylosis capsularis
      ossea. The clinical importance of the present findings is discussed in context
      with human literature.

PMID- 12507571
TI  - Tremorgenic mycotoxins increase gastric smooth muscle activity of sheep reticulum
      and rumen in vitro.
AB  - Reticulum and rumen strips (consisting of both muscle layers and the myenteric
      plexus) were superfused with Tyrode Ringer and their contractions recorded
      isometrically. The strips were subjected to exogenous acetylcholine and
      electrical field stimulation (EFS) resulting in contractions that could be
      blocked by atropine. Responses to the tremorgenic mycotoxin penitrem A and others
      thought to be involved in ryegrass staggers, paxilline and lolitrem B (10(-10)
      10(-6)M), were compared with those of control vehicle (0.1% DMSO). The tremorgens
      were without effect on quiescent preparations. Penitrem A and paxilline enhanced
      spontaneously active preparations and the amplitude of contractions in response
      to EFS. Responses to paxilline had a shorter latency than to penitrem A.
      Responses of spontaneously active preparations were resistant to atropine.
      Penitrem A, but not paxilline, increased responses to exogenous acetylcholine.
      Lolitrem B (10(-6)M) increased responses to EFS, but many responses were
      equivocal, possibly due to the lower solubility of lolitrem B in aqueous
      solutions compared to the other tremorgens. The results show that these
      mycotoxins have peripheral excitatory effects on the reticulorumen and it is
      suggested that such activity in vivo may reflexly affect centrally derived
      cyclical contractions.

PMID- 12507572
TI  - Genomic hypomethylation in neoplastic cells from dogs with malignant
      lymphoproliferative disorders.
AB  - DNA methylation is an epigenetic modification in which a methyl group is added
      usually to the fifth carbon position of a cytosine residue. Dysregulation of this
      process is an important molecular event which has been shown to be associated
      with neoplastic transformation and tumour progression in humans and mice.
      Features of methylation dysregulation in many different types of neoplasms
      include general genomic hypomethylation, focal hypermethylation, and altered
      expression of genes which encode a series of DNA (cytosine-5) methyltransferases.
      Interestingly, many types of neoplasia that are recognised in humans also develop
      spontaneously in the dog. By comparing the restriction patterns of MspI and
      HpaII, this study demonstrates that as in human, genomic hypomethylation is a
      feature of neoplastic cells in the majority of canine lymphoma cases and
      approximately one-third of canine leukemia cases confirming that dysregulation of
      the DNA methylating machinery is implicated in malignant transformation of
      lymphoid cells in some dogs.

PMID- 12507573
TI  - Guidelines for describing mouse skeletal phenotype.

PMID- 12507574
TI  - MicroCT evaluation of normal and osteoarthritic bone structure in human knee
      specimens.
AB  - Although trabecular bone structure has been evaluated, variation with knee
      compartment and depth from joint surface is not completely understood. Cadaver
      knees were evaluated with microcomputed tomography analysis for these variations.
      Objective differences were compared between: medial vs. lateral compartments;
      femoral vs. tibial bone; and normal vs. arthritic knees. Depth dependent changes
      in the parameters were observed for the first 6 mm of the cores in normal knees:
      BV/TV, Tb.N and Conn.D gradually decrease, while Tb.Sp and SMI increase. In the
      first 6 mm of the normal tibia BV/TV, Tb.N, and Tb.Th are greater than in the
      femur on both the medial and lateral compartments while Tb.Sp, SMI, and Conn.D
      are lower. The medial compartment values for BV/TV, Tb.N, Tb.Th and Conn.D are
      generally greater than for the lateral in both the femur and tibia while Tb.Sp
      and SMI are lower. In comparison of normal vs. arthritic knees significant
      differences are observed in the first 6 mm of the medial tibia. With arthritis
      BV/TV and Tb.Th are lower, while SMI and Tb.Sp are higher. Tb.N and Conn.D show
      no statistically significant difference. The bone structure variations are, thus,
      most prominent in the first 6 mm of depth and medial compartment bone is
      generally more structurally sound than lateral. Severely arthritic bone changes
      are most prominent in the medial compartment of the tibia and bone structure is
      less sound in severe arthritis.

PMID- 12507575
TI  - Effects of nicotine on bone mass and strength in aged female rats.
AB  - This study investigated the effects of nicotine on bone mass and biomechanical
      properties in aged, estrogen-replete (sham-operated) and estrogen-deplete
      (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and
      ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish
      cancellous osteopenia in the ovariectomized group. The animals were then
      administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0
      mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were
      collected at necropsy for determination of bone mass and strength. As expected,
      ovariectomy had a negative effect on most endpoints evaluated. Vertebral body
      bone mineral content (BMC) and density (BMD) and the structural (ultimate load
      and yield load) and material (ultimate stress, yield stress, and flexural modulus
      of elasticity) strength properties were lower in the OVX rats than in the sham
      operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus
      were also lower in the OVX rats than in the sham-operated rats. The nicotine
      doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold
      greater than those observed in heavy smokers. Despite the high doses used,
      nicotine had no effect on vertebral BMC, BMD, or any of the structural and
      material strength properties in either the OVX or the Sham rats. In addition,
      nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness,
      ultimate stress, or flexural modulus. Femoral yield load and stress were lower in
      low dose nicotine-treated rats than in vehicle-treated rats. However, differences
      were not detected between the high dose nicotine- and vehicle-treated rats for
      either femoral yield load or stress. The results suggest that tobacco agents
      other than nicotine are responsible for the decreased bone density and increased
      fracture risk as observed in smokers.

PMID- 12507576
TI  - Expression of smooth muscle actin in cells involved in distraction osteogenesis
      in a rat model.
AB  - Distraction osteogenesis has proven to be of great value for the treatment of a
      variety of musculoskeletal problems. Little is still known, however, about the
      phenotypic changes in the cells participating in the bone formation process,
      induced by the procedure. Recent findings of the expression of a contractile
      muscle actin isoform, alpha-smooth muscle actin (SMA), in musculoskeletal
      connective tissue cells prompted this immunohistochemical study of the expression
      of SMA in cells participating in distraction osteogenesis in a rat model. The
      tissues within and adjacent to the distraction site could be distinguished
      histologically on the basis of cell morphology, density, and extracellular matrix
      make-up. The percentage of SMA-containing cells within each tissue zone was
      graded from 0 to 4. The majority of the cells in each of the zones stained
      positive for SMA within five days of the distraction period. The SMA-containing
      cells included those with elongated morphology in the center of the distraction
      site and the active osteoblasts on the surfaces of the newly forming bone. These
      finding warrant further investigation of the role of this contractile actin
      isoform in distraction osteogenesis and investigation of the effects of
      modulation of this actin isoform on the procedure.

PMID- 12507577
TI  - Rapid new bone tissue remodeling during distraction osteogenesis is associated
      with apoptosis.
AB  - During the process of distraction osteogenesis new bone forms and undergoes rapid
      remodeling. Apoptosis may be one of the regulatory mechanisms governing the
      removal of the redundant callus during distraction osteogenesis. A rabbit tibial
      lengthening model was used and lengthened at 0.7 mm/day for 3 weeks. The
      regenerating tissues from the distraction gap were examined for apoptotic changes
      by transmission electron microscopy (TEM) and the terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Osteoclastic
      bone resorption activities were demonstrated by tartrate resistant acid
      phosphatase (TRAP) staining. The apoptotic cells were mainly present in the
      transitional regions between the fibrous tissue and the new bone in the
      mineralization front, and close to or on the new bone surfaces near the center of
      the regenerate. The TUNEL labeling was greatly reduced in the mature bone near
      the osteotomied bone ends. TEM examination confirmed the presence of cells with
      apoptotic changes at various regions of the regenerate. TRAP staining revealed
      that osteoclastic bone resorption activities in the regenerate were in a similar
      pattern of distribution to those of the TUNEL labeling. The localization of
      apoptotic cells at the different regions of the regenerate, accompanied by the
      osteoclast activities, suggest that apoptosis is closely related to bone
      formation and remodeling during distraction osteogenesis.

PMID- 12507578
TI  - Nerve conduction and microanatomy in the rabbit sciatic nerve after gradual limb
      lengthening-distraction neurogenesis.
AB  - To clarify how the peripheral nerve adapts to elongation during gradual limb
      lengthening, electrophysiological and histomorphometric examinations were
      performed on the sciatic nerves in 18 rabbits. External fixators were used to
      lengthen the right femora by 30 mm (30%), at a daily rate of 0.5 mm (Group 1) or
      2.0 mm (Group 2). Examinations were performed immediately after the limb
      lengthening procedure. Electrophysiologically, mild conduction slowing was
      observed in Group 1; a conduction block was evident in Group 2. Histologically,
      the mean diameter of myelinated fibers was unchanged in Group 1, but a
      significantly decreased diameter was observed in Group 2. Electron microscopy
      revealed that mild degenerative change of unmyelinated axons occurred
      sporadically in two cases in Group 2, but neither group showed evidence of
      thinning of myelin sheath of myelinated fibers. The mean internodal length
      (between nodes of Ranvier) of teased fibers was 1216+/-295 microm in the control
      contralateral side, 1484+/-347 microm in Group 1, and 1467+/-322 microm in Group
      2. Thus the internodes were lengthened by 22.1% (Group 1) and 20.7% (Group 2) in
      comparison with those of the controls. Straightening of the geometry of paranodal
      myelin sheath was significantly correlated with the rate of distraction. These
      results indicate that myelinated nerve fibers adapt to gradual elongation by
      lengthening each Schwann cell body, not by proliferation of Schwann cells.

PMID- 12507579
TI  - Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in
      rats.
AB  - Bone marrow derived mesenchymal stem cells (MSC) have been shown to be progenitor
      cells for mesenchymal tissues. These cells may also provide a potential therapy
      for bone repair. Our previous studies showed that MSC engineered with the gene
      for bone morphogenetic protein 2 (BMP-2), a growth factor for bone cells, were
      capable of differentiating into osteoblast lineage and inducing autologous bone
      formation in several animal models. Culturing individual MSC for autologous
      implantation, however, remains problematic. The number of human MSC with
      osteogenic potential decreases with age, and, in certain diseases, the patient's
      marrow may be damaged or the healthy cells reduced in number. In this study, we
      used rats with a femoral segmental defect to investigate whether allogeneic BMP-2
      engineered MSC would facilitate bone healing. We show that BMP-2 engineered
      allogeneic MSC can repair critical bone defects to the same degree as rats
      treated with BMP-2 engineered autologous MSC, if the allogeneic group receives
      short-term treatment with immunosuppressant FK506. We also show that allogeneic
      gene transferred MSC are directly involved in bone repair, in addition to acting
      as gene deliverers.

PMID- 12507580
TI  - The fate of soft callus chondrocytes during long bone fracture repair.
AB  - Following fracture, the cartilaginous tissue of the soft callus is eventually
      replaced by bone. Removal of the cartilage is a critical part of the bone healing
      process but information concerning the changes in chondrocytes during this
      process is sparse. The aim of the study was to investigate the fate of
      chondrocytes in the soft callus during the bone repair process using a rabbit
      tibial fracture model. Fracture tissue was processed for collagen I-III and
      keratan sulphate immunohistochemistry to study changes in matrix composition and
      the TUNEL technique (terminal deoxynucleotidyl transferase medicated dUTP nick
      end labelling) to identify death of soft callus chondrocytes. Transmission
      electron microscopy (TEM) was also carried out to investigate the ultrastructure
      of chondrocytes within the soft callus. Results showed that the size of the
      cartilage area decreased over time and that cartilage matrix was replaced with
      new matrix rich in collagen I and III. Chondrocytes became engulfed in the new
      matrix and appeared to stop producing cartilage matrix. Chondrocyte cell death
      was seen at the border of the soft callus, just within the newly produced matrix.
      TEM revealed that these dying/dead cells were not typically apoptotic in
      appearance. In conclusion, results indicate that chondrocytes of the soft callus
      die as a result of the progressive production of bone matrix which eventually
      engulfs them and leads to the remodelling of the area and eventual bone repair.

PMID- 12507581
TI  - Differences in the cytokine profiles associated with prostate cancer cell induced
      osteoblastic and osteolytic lesions in bone.
AB  - Prostate adenocarcinoma is associated with the formation of osteoblastic
      metastases in bone. It is hypothesized that osteoclastogenesis is a critical
      component in the development of skeletal metastases. These findings, however,
      were generally noted in predominantly osteolytic lesions. The pathophysiology of
      osteoblastic lesions remains unknown but the type of bone lesion formed may be
      influenced by the cytokines produced by prostate tumors. To test this theory, we
      implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were
      sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis
      was performed on these tibias. PCR analysis was also performed on bulk tumors.
      The results showed that the PC-3 implanted tibias developed pure osteolytic
      lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on
      radiographs. Analysis of tibias after injection with PC-3 cells revealed
      progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and
      destruction of the proximal tibia at 6 weeks after cell implantation. In
      contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell
      injection. There were rare osteoclasts prior to the establishment of the
      osteoblastic lesions but greater osteoclast activity was noted with remodeling of
      the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR
      analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are
      associated with osteoclastogenesis. In contrast, LAPC-9 cells produced
      osteoprotegerin, which blocks osteoclast production and no detectable levels of
      RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells
      secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These
      results suggest that the role of the osteoclast in the development of a
      metastatic lesion is variable depending on the phenotype of the prostate cancer
      cells, and that tumor-induced osteolysis may not be required for osteoblastic
      metastases.

PMID- 12507582
TI  - Two distinct cellular mechanisms of osteoclast formation and bone resorption in
      periprosthetic osteolysis.
AB  - PURPOSE: TNFalpha and IL-1alpha are proinflammatory cytokines that are abundant
      in periprosthetic tissues. These cytokines stimulate bone resorption and have
      recently been shown to directly induce osteoclast formation in mouse marrow
      cultures. We examined whether TNFalpha and IL-1alpha can directly induce
      osteoclast formation from human arthroplasty-derived (CD14(+)) macrophages by a
      mechanism independent of RANKL-induced osteoclastogenesis. METHODS: TNFalpha and
      M-CSF (+/-IL-1alpha) were added to cultures of magnetically sorted (CD14(+)) and
      unsorted (CD14(+)/CD14(-)) cells isolated from the pseudomembrane of loosened hip
      arthroplasties. Osteoprotegerin (OPG), RANK:Fc and antibodies to TNF receptors
      (p55 and p75) were added to these cultures to distinguish the pathway of
      osteoclastogenesis. Osteoclast differentiation was assessed by expression of
      tartrate-resistant acid phosphatase (TRAP), vitronectin receptor (VNR) and
      lacunar resorption. RESULTS: The addition of TNFalpha (+/-IL-1alpha) resulted in
      differentiation of CD14(+) macrophages into TRAP(+) and VNR(+) multinucleated
      cells capable of extensive lacunar resorption. Both OPG and RANK:Fc (which
      inhibit RANKL-induced osteoclastogenesis) did not block osteoclastogenesis. The
      addition of antibodies directed against the p55 receptor subunit of TNF resulted
      in significant inhibition of osteoclast formation and lacunar resorption.
      CONCLUSIONS: Our results indicate that, in the presence of M-CSF, TNFalpha is
      sufficient for inducing human osteoclast differentiation from arthroplasty
      macrophages and that TNFalpha acts synergistically with IL-1alpha to stimulate
      lacunar resorption. This process is distinct from the RANK/RANKL signalling
      pathway and is likely to operate in periprosthetic tissues when there is heavy
      wear particle deposition and cytokine production.

PMID- 12507583
TI  - Effect of pamidronate on the stimulation of macrophage TNF-alpha release by ultra
      high-molecular-weight polyethylene particles: a role for apoptosis.
AB  - The demonstration that one of the mechanisms of action of bisphosphonates (BPs)
      is the induction of osteoclast and macrophage apoptosis, suggests a potent
      therapeutic role for the BPs and other apoptosis-modulating agents in the
      management of periprosthetic osteolysis. The purpose of this study was to improve
      our understanding of the basic underlying molecular events leading to the
      inhibitory effect of pamidronate on the macrophage response to ultra-high
      molecular-weight polyethylene (UHMWPE) particles. Murine J774 macrophages were
      incubated for 0-72 h in the presence of UHMWPE particles and/or pamidronate. TNF
      alpha release was measured by ELISA while poly(ADP-ribose)polymerase (PARP)
      expression was measured by Western blot. DNA was analyzed on agarose. The
      appearance of PARP fragment and the fragmentation of DNA were used as markers of
      apoptosis. We observed a dose-dependent response to UHMWPE particles with TNF
      alpha release reaching 4, 10, and 19 times control with 10, 25, and 125
      particles/macrophage, respectively. UHMWPE particles (25 particles/macrophage)
      stimulate TNF-alpha release by a factor of 10, 7, and 6 after 24, 48, and 72 h,
      respectively, indicating a rapid stimulating effect of UHMWPE particles on TNF
      alpha release. Our results also showed that at 10 particles/macrophage,
      pamidronate inhibits UHMWPE-induced TNF-alpha release by 12%, 14%, and 23%
      respectively after 24, 48, and 72 h (p<0.05 vs. 24 and 48 h). With 25
      particles/macrophage, the inhibition of TNF-alpha reached 9%, 12%, and 15% after
      24, 48, and 72 h (p<0.05 vs. 24 h), respectively. There is no significant
      difference between the inhibition by pamidronate of TNF-alpha release induced by
      125 particles/macrophages at 24, 48, and 72 h. When cells are pre-incubated for
      48 h with pamidronate prior to addition of UHMWPE particles for 24 h, we observed
      an increased inhibition of TNF-alpha compared to the co-incubation protocol. The
      inhibiting effect of pamidronate reaches 56% when pre-incubated with macrophages
      prior to incubation with 10 particles of UHMWPE/macrophage (p<0.05 vs. co
      incubation).Co-incubation of pamidronate with UHMWPE particles also led to the
      appearance of the proteolytic PARP fragment after 24 h incubation. We also
      demonstrated the stimulation of DNA fragmentation (DNA laddering) after 48-72 h
      with pamidronate. The proteolytic cleavage of PARP, an early event in the
      induction of apoptosis, precedes the inhibition of UHMWPE particle-induced TNF
      alpha release by pamidronate whereas the fragmentation of DNA, a late apoptotic
      event, parallels this inhibition. Our results suggest the induction of macrophage
      apoptosis is associated with the inhibitory effect of pamidronate on TNF-alpha
      release. There is a need for the development of medical management of
      periprosthetic osteolysis. The demonstration that drugs such as pamidronate
      induce specific apoptosis-related pathways in macrophages contributes data for a
      rational approach in the treatment and/or prevention of periprosthetic
      osteolysis.

PMID- 12507584
TI  - Temporal effects of cell adhesion on mechanical characteristics of the single
      chondrocyte.
AB  - Cell adhesion to material surfaces is a fundamental phenomenon in tissue response
      to implanted devices, and an important consideration in tissue engineering. For
      example, elucidation of phenomena associated with adhesion of chondrocytes to
      biomaterials is critical in addressing the difficult problem of articular
      cartilage regeneration. The first objective of this study was to measure the
      mechanical adhesiveness characteristics of individual rabbit articular
      chondrocytes as a function of seeding time to provide further understanding of
      the cell adhesion process. The second objective was to quantify the force
      required to separate the plasma membrane from the underlying cytoskeleton as a
      function of seeding time. After culturing chondrocytes on glass coverslips for 1,
      2, 4, 6 h, two biomechanical tests were performed on single chondrocytes: (i)
      mechanical adhesiveness measurement by the cytodetacher; and (ii) plasma membrane
      tether formation force measurement by optical tweezers. Cell mechanical
      adhesiveness increased from 231+/-149 Pa at 1 h to 1085+/-211 Pa at 6 h. The cell
      contact area with the substrata increased from 161+/-52 microm(2) at 1 h to 369+/
      105 microm(2) at 6 h. The tether formation force increased from 232+/-23 pN at 1
      h to 591+/-17 pN at 6 h. Moreover, fluorescence staining by rhodamine-phalloidin
      demonstrated the process of actin spreading within the cytoskeleton from 0.5 to 6
      h and allowed for measurement of cell height which was found to decrease from
      12.3+/-2.9 microm at 0.5 h to 6.2+/-0.9 microm at 6 h.

PMID- 12507585
TI  - Quantification of expression levels of cellular differentiation markers does not
      support a general shift in the cellular phenotype of osteoarthritic chondrocytes.
AB  - Many studies have shown increased anabolic activity in osteoarthritic cartilage
      and have suggested changes in the cellular phenotypes of articular chondrocytes.
      Most of these studies relied on non-quantitative technologies, which did not
      allow the estimation of the relative importance of the different differentiation
      phenomena. In the present study, we developed and used quantitative PCR assays
      for collagen types I, II(total), IIA, III, and X as marker genes indicating
      cellular synthetic activity (collagen type II) as well as differentiation pattern
      of chondrocytes (collagen types I, IIA, III, and X) and quantified these genes in
      normal, early degenerative, and late stage osteoarthritic cartilage in parallel.
      At first sight, our results confirmed previously published data showing hardly
      any expression of collagen genes in normal and significantly enhanced expression
      in osteoarthritic cartilage. This included collagen types II, III, and IIA, but
      also collagen types I(alpha1) and X. However, if one considers the ratios of the
      various markers of chondrocytic differentiation in comparison to collagen type
      II, the main synthetic product of differentiated chondrocytes, no shift in the
      cellular phenotype was detectable. In fact, expression ratios remained constant
      or were even decreased in osteoarthritic cartilage. Our results confirm that
      normal adult human articular chondrocytes display hardly any expression activity
      of the collagen types investigated, whereas osteoarthritic chondrocytes show very
      increased synthetic activity. The largely unchanged ratios of collagen subtypes
      investigated indicate that no general shift in the cellular phenotype does occur
      in osteoarthritic cartilage as suggested by previous investigations.

PMID- 12507586
TI  - Epigallocatechin-3-gallate selectively inhibits interleukin-1beta-induced
      activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase
      in human osteoarthritis chondrocytes.
AB  - Activation of mitogen activated protein kinases (MAPK) is a critical event in pro
      inflammatory cytokine-induced signaling cascade in synoviocytes and chondrocytes
      that lead to the production of several mediators of cartilage damage in an
      arthritic joint. Green tea (Camellia sinensis) is a widely consumed beverage and
      we earlier showed that polyphenols present in green tea (GTP) inhibit the
      development of inflammation and cartilage damage in an animal model of arthritis.
      In this study we evaluated the role of epigallocatechin-3-gallate (EGCG), a green
      tea polyphenol which mimics its anti-inflammatory effects, in modulating the IL
      1beta-induced activation of MAPK's in human chondrocytes. We discovered that EGCG
      inhibited the IL-1beta-induced phosphorylation of c-Jun N-terminal kinase (JNK)
      isoforms, accumulation of phospho-c-Jun and DNA binding activity of AP-1 in
      osteoarthritis (OA) chondrocytes. Also IL-1beta, but not EGCG, induced the
      expression of JNK p46 without modulating the expression of JNK p54 in OA
      chondrocytes. In immunecomplex kinase assays, EGCG completely blocked the
      substrate phosphorylating activity of JNK but not of p38-MAPK. EGCG had no
      inhibitory effect on the activation of extracellular signal-regulated kinase
      p44/p42 (ERKp44/p42) or p38-MAPK in OA chondrocytes. EGCG or IL-1beta did not
      alter the total non-phosphorylated levels of either p38-MAPK or ERKp44/p42 in OA
      chondrocytes. These are novel findings and indicate that EGCG may be of potential
      benefit in inhibiting IL-1beta-induced catabolic effects in OA chondrocytes that
      are dependent on JNK activity.

PMID- 12507587
TI  - Mechanoregulation of human articular chondrocyte aggrecan and type II collagen
      expression by intermittent hydrostatic pressure in vitro.
AB  - This study addressed the hypothesis that duration and magnitude of applied
      intermittent hydrostatic pressure (IHP) are critical parameters in regulation of
      normal human articular chondrocyte aggrecan and type II collagen expression.
      Articular chondrocytes were isolated from knee cartilage and maintained as
      primary, high-density monolayer cultures. IHP was applied at magnitudes of 1, 5
      and 10 MPa at 1 Hz for durations of either 4 h per day for one day (4 x 1) or 4 h
      per day for four days (4 x 4). Total cellular RNA was isolated and analyzed for
      aggrecan and type II collagen mRNA signal levels using specific primers and
      reverse transcription polymerase chain reaction (RT-PCR) nested with beta-actin
      primers as internal controls. With a 4x1 loading regimen, aggrecan mRNA signal
      levels increased 1.3- and 1.5-fold at 5 and 10 MPa, respectively, relative to
      beta-actin mRNA when compared to unloaded cultures. Changing the duration of
      loading to a 4x4 regimen increased aggrecan mRNA signal levels by 1.4-, 1.8- and
      1.9-fold at loads of 1, 5 and 10 MPa, respectively. In contrast to the effects of
      IHP on aggrecan, type II collagen mRNA signal levels were only upregulated at
      loads of 5 and 10 MPa with the 4x4 loading regimen. Analysis of cell-associated
      protein by western blotting confirmed that IHP increased aggrecan and type II
      collagen in chondrocyte extracts. These data demonstrate that duration and
      magnitude of applied IHP differentially alter chondrocyte matrix protein
      expression. The results show that IHP provides an important stimulus for
      increasing cartilage matrix anabolism and may contribute to repair and
      regeneration of damaged or diseased cartilage.

PMID- 12507588
TI  - Protective effects of intermittent hydrostatic pressure on osteoarthritic
      chondrocytes activated by bacterial endotoxin in vitro.
AB  - The role of continuous passive motion (CPM) in the management of septic arthritis
      and inflammatory arthritis remains of interest. CPM produces cyclic variations in
      intraarticular pressure that facilitates transport of fluid, nutrients, and
      solutes within and/or across the joint and stimulates chondrocyte metabolism.
      However, the precise mechanisms mediating the responses of chondrocytes to joint
      motion remain unclear. This study tested the hypothesis that dynamic mechanical
      loading counteracts effects of bacterial lipopolysaccharide (LPS), an
      inflammatory mediator, on chondrocyte metabolism. Intermittent hydrostatic
      pressure (IHP) (10 MPa for 4 h) was applied to human chondrocytes pretreated with
      LPS (1 microg/ml for 18 h). LPS activation of chondrocytes decreased mRNA signal
      levels of type II collagen by 67% and aggrecan by 56% and increased nitric oxide
      by 3.1-fold, monocyte chemotactic protein-1 mRNA signal levels by 6.5-fold, and
      matrix metalloproteinase-2 mRNA signal levels by 1.3-fold. Application of IHP to
      LPS-activated chondrocytes decreased nitric oxide synthase mRNA signal levels and
      nitric oxide levels in the culture medium. Exposure of LPS-activated chondrocytes
      to IHP upregulated type II collagen and aggrecan mRNA signal levels by 1.7-fold,
      relative to chondrocytes activated by LPS and maintained without loading. In
      addition, application of IHP decreased the upregulation in signal levels of
      monocyte chemotactic factor-1 and matrix metalloproteinase-2 following LPS
      activation by 45% and 15%, respectively. These data show that mechanical loading
      counteract effects of inflammatory agents, such as bacterial LPS, and suggest
      that postinfection sequelae are influenced by the presence or absence of joint
      loading.

PMID- 12507589
TI  - Expanded phenotypically stable chondrocytes persist in the repair tissue and
      contribute to cartilage matrix formation and structural integration in a goat
      model of autologous chondrocyte implantation.
AB  - Autologous chondrocyte implantation (ACI) is an established technique to repair
      joint surface defects. Although there is some indirect evidence that the expanded
      chondrocytes are required to achieve proper healing, the role they play in the
      repair process is not clear yet. To monitor the persistence and the phenotype of
      the injected chondrocytes in the repair tissue (RT) we have optimized a
      fluorescent labeling protocol for articular chondrocytes, which allows cell
      tracking in vivo for up to 14 weeks, using the fluorescent dye PKH26. We have
      combined in vivo cell tracking, with the immune-detection of collagen type II
      protein in a goat model of ACI. Our data indicate that the implanted cells can
      persist for at least 14 weeks in the defects, can participate in the integration
      with the surrounding tissues, and become structural part of the RT, rich in
      collagen type II and sulfated proteoglycans. Albeit with a small number of
      samples, our data provide proof of principal that the implanted chondrocytes can
      contribute to structural cartilage repair in a goat model of ACI.

PMID- 12507590
TI  - The use of specific chondrocyte populations to modulate the properties of tissue
      engineered cartilage.
AB  - Tissue engineering of articular cartilage is a promising alternative to the
      conventional approaches for cartilage repair. However, recent attempts to develop
      articular cartilage in vitro have proven to be difficult. The tissue formed in
      vitro may not accumulate enough extracellular matrix, and the resulting
      mechanical properties are only a fraction of the native tissue. We investigated
      whether using specific populations of chondrocytes would improve the properties
      of the cartilaginous tissue that was generated in vitro. Full-thickness (FT), mid
      and-deep zone (MD), and deep-zone (DEEP) chondrocytes were isolated, placed on
      the surface of porous ceramic substrates and maintained in culture for eight
      weeks. Tissue developed from DEEP chondrocytes was thicker (FT: 0.94+/-0.03, MD:
      0.88+/-0.04, DEEP: 2.4+/-0.1 mm) and had accumulated larger amounts of
      extracellular matrix (FT: 1.61+/-0.05, MD: 1.5+/-0.1, DEEP: 3.8+/-0.2 mg dry
      weight) than the tissues formed by the FT and MD chondrocytes. The tissue formed
      by the FT chondrocytes accumulated the greatest amount of collagen (FT: 211+/-14,
      MD: 185+/-8, DEEP: 178+/-5 microg/mg dry weight) whereas the tissue formed by the
      MD chondrocytes accumulated significantly more proteoglycans (FT: 198+/-10, MD:
      265+/-10, DEEP: 215+/-5 microg/mg dry weight). Interestingly, MD chondrocytes
      produced tissue that had compressive mechanical properties up to four times
      greater than the cartilaginous tissues formed by cells from either the FT or DEEP
      of cartilage. Thus, a combined population of intermediate and DEEP chondrocytes
      might be more suitable for the tissue engineering of articular cartilage.

PMID- 12507591
TI  - A novel two-step method for the formation of tissue-engineered cartilage by
      mature bovine chondrocytes: the alginate-recovered-chondrocyte (ARC) method.
AB  - Most attempts to tissue-engineer cartilage have involved seeding of cultured
      cells into a biological or synthetic scaffold. We have developed a novel two-step
      culture approach that makes possible the in vitro formation of cartilaginous-like
      tissue by mature adult bovine chondrocytes without the aid of a synthetic matrix.
      The first step consists of culturing chondrocytes under conditions that maintain
      their rounded shape and their molecular phenotype as assessed by type II collagen
      and aggrecan production. This step was accomplished by culturing the isolated
      chondrocytes in alginate beads until the cells have reestablished a proteoglycan
      rich cell-associated matrix (CM). The second step consists of culturing the cells
      with their CM, after recovery from the beads, on a tissue culture insert with a
      porous membrane. In this study, young adult bovine articular chondrocytes were
      cultured in alginate beads in the presence of 10% or 20% fetal bovine serum
      (FBS). After 7 days of culture, the alginate beads were dissolved by incubating
      the beads for 20 min in sodium citrate buffer, a calcium chelator. Following a
      brief centrifugation, the cells with their CM were recovered, resuspended in
      medium containing 10% or 20% FBS and seeded onto a tissue culture insert. After 1
      week of culture on the insert, the individual cells with their CM progressively
      became incorporated into a mass of cartilaginous tissue. Culture with 20% FBS
      resulted in the best formation of tissues. These tissues, easily recovered from
      the insert, were then subjected to biochemical and histological analyses. The
      biochemical results showed that the chondrocytes remain phenotypically stable in
      the tissues. The de novo tissue has a relatively high ratio of PG/collagen.
      Histological examination of the tissue revealed it contained a cartilage-like
      matrix strongly stained with toluidine blue. This scaffold-free system appears
      ideal to study, in vitro, the development of transplantable cartilaginous tissue.

PMID- 12507592
TI  - Evaluation of collagen fiber maturation and ordering in regenerating tendons
      employing H-1 double quantum filtered NMR spectroscopy.
AB  - It is difficult to monitor the chronic stage of the healing process of ruptured
      tendons employing the present diagnostic modes. However, the results of this
      study have shown that 1H double quantum filtered (DQF) NMR spectroscopy is
      sensitive to the later stages of the healing process. Regenerated tendons of
      rabbits were dissected and measured at the end of the acute phase (three weeks),
      the subacute phase (nine weeks), and the chronic phase (13 and 18 weeks after
      tenotomy). Four parameters were determined by 1H DQF NMR spectroscopy: (a) the
      maximum signal intensity (h(max)) relative to the single quantum spectrum, (b)
      the creation time of the maximum signal intensity (tau(max)), (c) the decay time
      from the maximum signal intensity to a value half of that intensity (tau(1/2))
      and (d) the residual dipolar splitting of water (delta), representing the order
      of the collagen fibers. The values of h(max), tau(max), tau(1/2), and delta of
      the intact Achilles tendons were 11.3+/-1.0%, 0.48+/-0.03 ms, 0.67+/-0.04 ms and
      732+/-62 Hz (mean +/- SEM, n=6), respectively. In the regenerating tendon, h(max)
      increased from 0.41+/-0.12% at three weeks to 7.07+/-0.77% at 18 weeks, tau(max)
      decreased from 1.88+/-0.31 ms at three weeks to 0.72+/-0.04 ms at 18 weeks,
      tau(1/2) decreased from 11.6+/-1.8 ms at 3 weeks to 1.48+/-0.16 ms at 18 weeks,
      and delta increased from 129+/-8 Hz at three weeks to 414+/-29 Hz at 18 weeks. We
      have concluded that reordering of collagen fibers proceeds continuously even in
      the chronic stage of healing. Thus, the 1H DQF NMR spectroscopy is a useful non
      invasive technique to evaluate the reconstruction and the order of collagen
      fibers in regenerating tendon. It is also suggested that tau(1/2) and h(max) are
      most useful for in vivo DQF NMR spectroscopy and imaging, respectively, in
      combination with tau(max).

PMID- 12507593
TI  - Inhibition of cell migration from tendon explants into fibrin clots by extracts
      derived from cheese whey is largely due to transforming growth factor-beta.
AB  - Whey-derived growth factor extract (WGFE) and the acid-activated form (WGFE-a)
      were tested for their ability to influence the migration of cells from chicken
      flexor tendon biopsies into fibrin clots. When added to the medium surrounding
      clots, both extracts significantly inhibited migration relative to controls
      (P<0.05) in a dose-dependent manner when measurements were made after seven days
      of incubation. WGFE-a was approximately ten times more potent than WGFE. Since
      transforming growth factor (TGF)-beta1 and -beta2 activity of WGFE-a is much
      higher than in WGFE we hypothesized that TGF-beta was responsible for the
      inhibition of tendon cell migration. Neutralizing anti-TGF-beta monoclonal
      antibody was added to the medium bathing tendon biopsies in fibrin clots along
      with WGFE-a. WGFE-a alone inhibited migration by 51% and this was reversed by the
      antibody in a dose-dependent manner. Furthermore, recombinant human TGF-beta1 and
      -beta2 significantly inhibited tendon cell migration with similar dose-dependent
      potency when tested in the assay. These results indicate that TGF-beta is largely
      responsible for the inhibition of tendon cell migration by WGFE-a. This sheds
      further light on the functions of this growth factor during the early events in
      tendon repair.

PMID- 12507594
TI  - Gliding properties of the long head of the biceps brachii.
AB  - To elucidate the role of mechanical forces that resist motion of the long head of
      the biceps brachii, the gliding resistance of the tendon during abduction and
      adduction was measured. Nine human cadaveric glenohumeral joints were obtained
      (mean age 68 years, range 47-84). A testing device was developed to simulate
      glenohumeral abduction and adduction motion. Gliding resistance was calculated as
      the force differential on the proximal and distal ends of the biceps brachii at
      five glenohumeral angles (15 degrees, 30 degrees, 45 degrees, 60 degrees and 75
      degrees ). The average gliding resistance in abduction at 15 degrees, 30 degrees,
      45 degrees, 60 degrees and 75 degrees for a 4.9 N load was 0.41, 0.40, 0.36, 0.32
      and 0.28 N, respectively. At these same angles, but during adduction motion, the
      force on the proximal tendon end was either identical or less than the distal
      tendon end (p>0.46) indicating a lack of resistance and even a phenomena of
      "negative" resistance in which some other force overcame the friction. The
      difference in gliding resistance between abduction and adduction was significant
      (p<0.05). The results indicate that forces opposing biceps tendon gliding are
      more complicated than simply due to friction. Tendon deformation inside the
      bicipital groove produces a direction-dependent effect due to a mechanism of
      elastic recoil. Understanding forces that are absorbed by the tendon during
      active motion may provide insight into pathological changes that develop inside
      and around the tendon.

PMID- 12507595
TI  - Chronic repetitive reaching and grasping results in decreased motor performance
      and widespread tissue responses in a rat model of MSD.
AB  - This study investigated changes in motor skills and tissues of the upper
      extremity (UE) with regard to injury and inflammatory reactions resulting from
      performance of a voluntary forelimb repetitive reaching and grasping task in
      rats. Rats reached for food at a rate of 4 reaches/min, 2 h/day, and 3 days/week
      for up to 8 weeks during which reach rate, task duration and movement strategies
      were observed. UE tissues were collected bilaterally at weekly time points of 3-8
      weeks and examined for morphological changes. Serum was tested for levels of
      interleukin-1alpha (IL-1) protein. The macrophage-specific antibody, ED1, was
      used to identify infiltrating macrophages and the ED2 antibody was used to
      identify resident macrophages. Rats were unable to maintain baseline reach rate
      in weeks 5 and 6 of task performance. Alternative patterns of movement emerged.
      Fraying of tendon fibrils was observed after 6 weeks in the mid-forelimb. After 4
      weeks, a general elevation of ED1-IR macrophages were seen in all tissues
      examined bilaterally including the contralateral, uninvolved forelimb and
      hindlimbs. Significantly more resident macrophages were seen at 6 and 8 weeks in
      the reach limb. At 8 weeks, serum levels of IL-1alpha increased significantly
      above week 0. Our results demonstrate that performance of repetitive tasks
      elicits motor decrements, signs of injury and a cellular and tissue responses
      associated with inflammation.

PMID- 12507596
TI  - Biomechanical effects of medial-lateral tibial tunnel placement in posterior
      cruciate ligament reconstruction.
AB  - With most posterior cruciate (PCL) reconstruction techniques, the distal end of
      the graft is fixed within a tibial bone tunnel. Although a surgical goal is to
      locate this tunnel at the center of the PCL's tibial footprint, errors in medial
      lateral tunnel placement of the tibial drill guide are possible because the
      position of the tip of the guide relative to the PCL's tibial footprint can be
      difficult to visualize from the standard arthroscopy portals. This study was
      designed to measure changes in knee laxity and graft forces resulting from mal
      position of the tibial tunnel medial and lateral to the center of the PCL's
      tibial insertion. Bone-patellar tendon-bone allografts were inserted into three
      separate tibial tunnels drilled into each of 10 fresh-frozen knee specimens.
      Drilling the tibial tunnel 5 mm medial or lateral to the center of the PCL's
      tibial footprint had no significant effect on knee laxities; the graft pretension
      necessary to restore normal laxity at 90 degrees of knee flexion (laxity match
      pretension) with the medial tunnel was 13.8 N (29%) greater than with the central
      tunnel. During passive knee flexion-extension, graft forces with the medial
      tibial tunnel were significantly higher than those with the central tunnel for
      flexion angles greater than 65 degrees while graft forces with the central tibial
      tunnel were not significantly different than those with the lateral tibial
      tunnel. Graft forces with medial and lateral tunnels were not significantly
      different from those with a central tunnel for 100 N applied posterior tibial
      force, 5 Nm applied varus and valgus moment, and 5 Nm applied internal and
      external tibial torque. With the exception of slightly higher graft forces
      recorded with the medial tunnel beyond 65 degrees of passive knee flexion, errors
      in medial-lateral placement of the tibial tunnel would not appear to have
      important effects on the biomechanical characteristics of the reconstructed knee.

PMID- 12507597
TI  - An in vivo model of degenerative disc disease.
AB  - Although the precise etiology of low back pain is disputed, degeneration of the
      intervertebral disc is believed to play an important role. Many animal models
      have been described which reproduce the changes found in degenerative disc
      disease, but none allow for efficient, large-scale testing of purported
      therapeutic agents. The purpose of this study was to develop a simple animal
      model resembling degenerative disc disease using the intervertebral discs found
      in the tails of rats. The proximal two intervertebral discs in the tails of 20
      rats were injected with either chondroitinase ABC or control (phosphate buffered
      saline, PBS). The tails were harvested at 2 weeks, and measurements were made of
      intervertebral disc height (measured radiographically and histologically),
      biomechanics (stiffness, hysteresis, and residual deformation), and histologic
      appearance. Treatment with chondroitinase ABC resulted in a significant loss in
      intervertebral disc height (radiographic intervertebral disc height, p=0.001;
      histologic intervertebral disc height, p<0.001) and significant increases in all
      biomechanical parameters (stiffness, p<0.001; hysteresis, p=0.006; residual
      deformation, p=0.004) compared to PBS controls. Intervertebral discs treated with
      chondroitinase ABC had significantly lower histologic grades for each grading
      category (nucleus pulposus (NP), annulus fibrosus, and proteoglycan staining)
      compared to controls. The results of injury with chondroitinase ABC were similar
      to the findings in degenerative disc disease: reduced intervertebral disc height,
      diminished proteoglycan content, loss of NP cells, and increased stiffness of the
      disc. Thus, the model appears to be a reasonable tool for the preliminary in vivo
      evaluation of proposed treatments for degenerative disc disease.

PMID- 12507598
TI  - [Prevalence of HBV, HCV, HIV and HTLV in autologous blood donors in France
      between 1993 and 2000].
AB  - The epidemiological surveillance of autologous blood donors has been carried out
      in France since 1993. The number of autologous donors increased regularly from
      1993 to 1997 but has decreased during the last three years to become less than
      50,000 in 2000. The sex-ratio was stable over time (0.85 male for 1 female). The
      population of autologous donors grew older between 1993 and 2000: the proportion
      of those aged under 50 years old decreased from 29% in 1993 to 18% in 2000 while
      the proportion of those over 69 increased from 22 to 34%. Between 1993 and 2000,
      HbsAg prevalence decreased by a factor of 2.5 and HCV prevalence by a factor of
      5. For HIV, a slight decrease was observed and the prevalence of HTLV was stable
      over time. In 2000, HCV prevalence (0.23%) was two times higher than HBsAg
      prevalence (0.12%), fifteen times higher than HTLV prevalence in Continental
      France (0.015%) and one hundred times higher than HIV prevalence (0.002%). The
      prevalence was similar in men and women for HCV, about two times higher in men
      than in women for HBsAg and three times higher for HIV. On the contrary, HTLV
      prevalence was about two times higher in women than in men. HBsAg and HCV
      prevalence rates were also calculated by age group. The prevalence rates for
      HBsAg increased up to the 30-39 age group among women and the 40-49 age group
      among men; then the rates decreased but were higher in men than in women. For
      HCV, while the prevalence increased continuously with age among women, a peak was
      reached for men in the 30-39 age group followed by a decrease up to the 50-59 age
      group and the prevalence was stable afterwards. The very low level of the current
      risk of transmitting viral infections by homologous transfusion and technical
      changes in autologous transfusion seem to be the two main factors that
      contributed to the recent decline in the number of autologous donors. The
      decrease in HBsAg and anti-HCV prevalence between 1993 and 2000 is
      multifactorial, but the drop observed for HCV is probably linked to a decrease in
      HCV prevalence of the general population over the last ten years.

PMID- 12507599
TI  - [Specificity of immunofluorescent methods detecting malarial antibodies:
      comparative study in the screening of blood donations].
AB  - In France, no case of transfusion-transmitted malaria has been reported since
      1994, reflecting the efficiency of the blood donations screening. However, an
      insufficiently specific serological assay leads to an unjustified loss of red
      cell units. MATERIALS AND METHODS: A retrospective study included 55 sera
      previously disqualified for the presence of malarial antibodies. We used
      different assays detecting these antibodies: Paludix, Falciparum-Spot without or
      with the elimination of natural antiglobulins by two different methods. RESULTS:
      Using Paludix, 87% of sera were negative (P < 0.001). With the sera treated for
      the elimination of natural antiglobulins by neutralisation or absorption,
      Falciparum-Spot(TM) gave respectively 87% and 94.5% of negative results.
      CONCLUSION: When using assays avoiding non-specific fluorescence, the number of
      false positive results significantly decreased. Because the number of blood
      donors travelling in at-risk countries is continuously rising, a sufficiently
      specific method to detect malarial antibodies should save a lot of red cell
      units.

PMID- 12507600
TI  - [Cancer genetic immunotherapy].
AB  - The concept of cancer immunotherapy and the resulting technical advances have
      evolved considerably during the last decade. However, cancer treatment by
      recombinant IL-2 or IFN-alpha still represents today the best therapeutic way for
      the treatment of renal carcinoma, melanoma and in some cases lymphoma. The
      immunotherapy approaches such as vaccination, gene and cellular therapy, have not
      yet demonstrated a sufficient clinical efficacy for the treatment of solid
      tumors. The goal of this review is to summarize the different approaches to
      cancer immunotherapy developed today. Specific approaches such as antigenic
      vaccination will be first described, then non-specific approaches such as gene
      transfer on the tumor site of immuno-stimulating genes will be discussed.

PMID- 12507601
TI  - [Evaluation of scientific and medical articles].
AB  - Quality assessment of publications article is now teached during medical studies
      and will soon be included into the program of the internship examination. The
      impact factor of medical journals is frequently used to evaluate the scientific
      quality of an article and consequently as an index of scientific productivity.
      Impact factor is an indicator of citation but not of the quality of an article
      and should not be used as a unique criterion for evaluating the quality of
      medical or scientific research works.

PMID- 12507602
TI  - Effect of protein kinase C activation on Na+-H+ exchange in erythrocytes of frog
      Rana temporaria.
AB  - The treatment of frog erythrocytes incubated in standard nitrate medium with 100
      nM phorbol ester (PMA) induced a sharp increase in the 22Na uptake by the cells
      and intracellular Na(+) concentration. The PMA-induced enhancement in 22Na uptake
      was stimulated by the addition of 0.1 mM ouabain to the incubation medium and
      completely blocked by 1 mM amiloride. The time course of 22Na uptake by frog red
      cells in the presence of PMA showed a lag phase ( approximately 5 min), after
      which was linear within 5-15 min. The calculated Na(+) influx in erythrocytes
      treated with PMA was 49.4+/-3.7 mmol l(-1) cells h(-1) as compared with 1.2+/
      0.25 mmol l(-1) h(-1) for control cells. 5-(N-ethyl-N-isopropyl)-amiloride,
      selective blocker of NHE1, caused a dose-dependent inhibition of the PMA-induced
      Na(+) influx with IC(50) of 0.27 microM. The PMA-induced Na(+) influx was almost
      completely inhibited by 0.1 microM staurosporine, protein kinase C blocker.
      Pretreatment of frog red blood cells for 5, 10 or 15 min with 10 mM NaF, non
      selective inhibitor of protein phosphatase, led to a progressive stimulation of
      the PMA effect on Na(+) influx. Both amiloride and NaF did not affect the basal
      Na(+) influx in frog erythrocytes. The data indicate that the Na(+)-H(+)
      exchanger in the frog erythrocytes is quiescent under basal conditions and can be
      markedly stimulated by PMA.

PMID- 12507603
TI  - Liver and kidney structure and iron content in romanian brown bears (Ursus
      arctos) before and after hibernation.
AB  - The annual cycle of the brown bear (Ursus arctos) in the Carpathian Mountains
      (Romania) consists of an active period from April to November, and an inactive
      period (hibernation) of approximately 4-5 months between November and March.
      During hibernation, the brown bears sleep continually and do not feed or drink
      water. Analyses of liver and kidney of male brown bears showed that liver iron
      content was 3 times higher in bears at the end of hibernation than at the end of
      the active period. A possible trend towards a decrease in iron content was noted
      for the kidney. The presence of iron in the liver was confirmed by the presence
      of the Perls-positive granules in the cytoplasm of Kupffer cells, in other non
      parenchymal cells and also in some hepatocytes. The hepatic veins of the bear
      liver samples obtained in early spring showed narrower lumens with pleated walls,
      compared to the normal outline of the hepatic veins in the liver from the bears
      sampled during autumn. Also in the early spring bears, the renal glomeruli were
      partially fibrosed. Renal glomerular fibrosis was sometimes observed in samples
      from the prehibernation period. The tissue iron values from the livers and
      kidneys of brown bears in early spring or autumn might provide useful data on
      iron metabolism under conditions of hibernation and accompanying starvation.

PMID- 12507604
TI  - Atrial natriuretic peptide stimulates cat carotid body chemoreceptors in vivo.
AB  - It is known that atrial natriuretic peptide (ANP) is released from cardiac
      myocyte and other stores during hypoxia and is involved in pulmonary
      cardiovascular reflexes and in natriuresis and diuresis. Since the carotid body
      initiates hypoxic chemoreflexes, we hypothesized that ANP could potentiate the
      hypoxic stimulation of the carotid body chemoreceptor in vivo. We studied the
      effect of close intra-arterial injection of ANP on carotid chemoreceptor activity
      in anesthetized male cats which were paralyzed and artificially ventilated.
      Graded doses of ANP (0-10 nmoles) were administered by intra-arterial injections
      and they produced an excitatory response. Single dose of ANP (6.5 nmoles) at four
      steady-state levels of arterial PO(2), at constant PCO(2), produced increases of
      chemoreceptor activity. This increase of chemoreceptor activity with ANP in the
      presence of CO(2)-HCO(3)(-) in vitro could make a difference from those without
      CO(2)-HCO(3)(-) in vivo.

PMID- 12507605
TI  - Yolk proteins during ovary and egg development of mature female freshwater
      crayfish (Cherax quadricarinatus).
AB  - Vitellins from ovaries and eggs at different stages of development in freshwater
      crayfish (Cherax quadricarinatus) were examined by chromatography, PAGE and SDS
      PAGE. With these methods, two forms of vitellin (Vt1 and Vt2) were observed in
      ovaries and eggs (stages I and V). In ovaries in secondary vitellogenesis, native
      molecular mass was 470 (Vt1) and 440 (Vt2) kDa. The electrophoretic pattern of
      the eggs proved to be more complex. The protein molecular mass depend on the
      development stage of the egg: stage I, 650 kDa (Vt1) and 440 kDa (Vt2); stage V,
      390 kDa (Vt1) and 340 kDa (Vt2). The identified vitellins appear to be lipo
      glycocarotenoprotein. A similar vitellin polypeptide composition was observed in
      the two forms of vitellin from ovaries and eggs in stage V. In ovaries the SDS
      PAGE analysis showed four subunits with molecular weights of approximately 180,
      120, 95 and 80 kDa (Vt1 and Vt2). The polypeptide composition in the two forms of
      vitellins in stage I and stage III eggs were different at 195, 190, 130 and 110
      kDa (Vt1) and 116 and 107 kDa (Vt2). On the other hand, in stage V eggs, 110, 95,
      87 and 75 kDa (Vt1 and Vt2) were identified. Two antibodies (Ab1 and Ab2) were
      prepared against the purified proteins of stage V eggs and their specificity was
      demonstrated by radial immunoprecipitation, and Western blotting analysis. Two
      forms of vitellins were also found in stage V eggs after chromatography on
      Sepharose CL-2B column and hydroxylapatite and polyacrylamide gel
      electrophoresis.

PMID- 12507606
TI  - Oxygen transport capacity in the air-breathing fish, Megalops cyprinoides:
      compensations for strenuous exercise.
AB  - Tarpon have high resting or routine hematocrits (Hct) (37.6+/-3.4%) and
      hemoglobin concentrations (120.6+/-7.3 gl(-1)) that increased significantly
      following bouts of angling-induced exercise (51.9+/-3.7% and 142.8+/-13.5 gl(-1),
      respectively). Strenuous exercise was accompanied by an approximately tenfold
      increase in blood lactate and a muscle metabolite profile indicative of a high
      energy demand teleost. Routine blood values were quickly restored only when this
      facultative air-breathing fish was given access to atmospheric air. In vitro
      studies of oxygen transport capacity, a function of carrying capacity and
      viscosity, revealed that the optimal Hct range corresponded to that observed in
      fish under routine behaviour. During strenuous exercise however, further increase
      in viscosity was largely offset by a pronounced reduction in the shear-dependence
      of blood which conformed closely to an ideal Newtonian fluid. The mechanism for
      this behaviour of the erythrocytes appears to involve the activation of surface
      adrenergic receptors because pre-treatment with propranolol abolished the
      response. High levels of activity in tarpon living in hypoxic habitats are
      therefore supported by an elevated Hct with adrenergically mediated viscosity
      reduction, and air-breathing behaviour that enables rapid metabolic recovery.

PMID- 12507607
TI  - Some methodological aspects of metallothionein evaluation.
AB  - The specificity of the methods used for metallothioneins (MTs) determination in
      both field and laboratory studies is crucial to a relevant interpretation of the
      results. The technique applied in the present study is commonly used, but several
      potential problems may limit its validity: (i). the stability of the metal-SH
      links during heating and the possibility of metal exchanges between MTs and
      others compounds; (ii). the presence of heat-stable thiol compounds with high
      molecular weight or very low molecular weight, which may subsist in the
      supernatant and interfere during global analysis of MTs; (iii). the subsistence
      of metals not bound to MT in the supernatant after heating; and (iv). the impact
      of reducing agents such as mercaptoethanol on the metal-binding ligands. Our
      investigations were conducted mainly on oysters (Crassostrea gigas) and
      polychaetes (Hediste/Nereis diversicolor) sampled, respectively, in two French
      metal-rich sites, the Gironde estuary and Boulogne harbour. This study, which
      allowed us to clarify most of the potential problems noted above, indicates the
      importance of dealing with methodological difficulties.

PMID- 12507608
TI  - Comparative nutrient digestibility of arctic foxes (Alopex lagopus) on Svalbard
      and farm-raised blue foxes (Alopex lagopus).
AB  - Arctic foxes from Svalbard (n=4) and farmed blue foxes (n=4) was used in a
      digestibility experiment with a high-carbohydrate feed to add more information to
      the nutritional physiology of the arctic fox, and to compare its digestive
      capacity with that of the farmed blue fox. The arctic fox has a diet containing
      mainly protein and fat from mammals and birds, while farmed blue foxes have been
      exposed to an omnivorous dietary regime for more than 80 generations. The
      experiment showed in general no difference in digestive capacity for protein and
      fat between the foxes (P>0.05), but for carbohydrates, including starch and
      glucose, the blue fox revealed higher digestibility values. The superior
      digestive capacity for carbohydrates in blue fox might be a result of a long-term
      selection of animals digesting dietary carbohydrates more efficiently, or that an
      early age exposition to dietary carbohydrates has given permanent improvement of
      the carbohydrate digestion in the gut.

PMID- 12507609
TI  - The effect of feeding frequency on consumption of food, absorption efficiency,
      and gonad production in the sea urchin Lytechinus variegatus.
AB  - The frequency of feeding in the field is variable in sea urchins, ranging from
      nearly continuous to diel or intermittent. It is essential to know the effect of
      feeding interval on physiological and metabolic processes to understand the basis
      for production. Lytechinus variegatus (50 mm horizontal diameter) were collected
      in January 1999 and held in closed-circuit aquaria at 25 degrees C and 35 per
      thousand salinity. After 9 days without food, individuals were fed one of three
      treatments: food available ad libitum, food available for 1 day every 2 days or
      food available for 1 day every 4 days for 28 days. The rate of food consumption
      per day of all individuals was high the first week of feeding. It then decreased
      to a lower, constant rate in those fed ad libitum but remained high in those fed
      one day every 2 or 4 days. The total amount eaten was directly related to
      frequency of feeding. The apparent dry matter digestibility (absorption
      efficiency) did not vary with frequency of feeding. As the total amount of energy
      absorbed was directly related to the frequency of feeding, the increase in the
      rate of food consumption does not compensate for a decrease in frequency of
      feeding. Gonad production efficiency was directly related to frequency of
      feeding. Gonad gross production (assimilation) efficiencies were 8.4, 3.9 and
      3.4% for individuals fed every day, or fed one day every 2 and 4 days,
      respectively. The corresponding gonad net assimilation efficiencies were 12.5,
      5.5, and 4.8%. A decrease in frequency of food availability results in use of a
      greater proportion of the food consumed for maintenance and less for gonad
      production.

PMID- 12507610
TI  - Effects of season and temperature acclimation on electrocardiogram and heart rate
      of toads.
AB  - Electrocardiogram (ECG) was recorded from unrestrained toads of two species, one
      resistant (Bufo viridis) and the other sensitive (B. regularis) to low
      temperatures. Although the temperature-sensitive species could not survive at
      temperatures below 7-8 degrees C, heart rate is linearly and similarly related to
      ambient temperature in the two species. In B. viridis, the cold resistant
      species, heart rate in winter was 25% lower than in summer, and the dependency of
      heart rate on temperature was reduced by 50% in toads acclimated to 10 degrees C
      in winter. It was not possible to disclose any effect of acclimation on heart
      rate in summer, due to the large variation in the recorded values. The QRS
      amplitude in the ECG was considerably reduced at low temperature only in B.
      viridis. It is concluded that differences in cardiac activity cannot account for
      the distinct difference in thermal relations of the two species, and that it
      should reside at other regulatory levels.

PMID- 12507611
TI  - Effects of a fiber-rich diet on physiology and survival of farm-reared red-legged
      partridges (Alectoris rufa).
AB  - The sudden shift from a commercial energy-rich, fiber-poor diet to natural food
      is assumed as one of the causes of the low success of gamebird restocking. We fed
      farmed red-legged partridge (Alectoris rufa) chicks with a diet rich in fiber
      from their first month of life to the time of their release to assess the
      possible effects on morphometric characteristics and plasma biochemistry and
      whether those effects enhance survival after release into the wild. At the time
      of release, treated partridges showed heavier gizzards and bursas of Fabricius
      and longer small intestines than control birds fed commercial feed. Treated birds
      had also smaller pectoral muscles, lighter spleens and lower plasma levels of
      proteins, glucose, cholesterol and triglycerides. After release and radiotracking
      in a hunting area, we found no differences in the survival between both groups.
      Survival at the end of the study (day 39) was 58.3+/-14.2% for the control group
      and 24.2+/-13.8% for the treated group. The fiber-rich diet seems to have
      important effects on the physiology of the red-legged partridge, not always taken
      into account in previous studies.

PMID- 12507612
TI  - Effects of cysteamine--a somatostatin-inhibiting agent--on serum growth hormone
      levels and growth in juvenile grass carp (Ctenopharyngodon idellus).
AB  - Effects of cysteamine hydrochloride (CSH)-a somatostatin-inhibiting agent-on
      serum growth hormone (GH) levels and growth in juvenile grass carp
      (Ctenopharyngodon idellus) were studied. Intraperitoneal (i.p.) injection and
      single or 10-day feeding of different doses of CSH significantly increased serum
      GH levels. CSH and luteinizing hormone-releasing hormone analog (LHRH-A, D
      Ala(6),Pro(9)-Net-LHRH), alone and in combination i.p. injection, and single or
      10-day administration in diet resulted in an enhancement of serum GH contents; in
      addition, there was an additive, not synergistic effect of CSH and LHRH-A on
      elevation of serum GH levels. Ten day feeding of CSH, or CSH and LHRH-A, alone
      and in combination caused a significant increase in muscle RNA/DNA ratio. These
      results provide evidence that CSH significantly increases serum GH levels and
      promotes short-term growth in juvenile grass carp.

PMID- 12507613
TI  - Energetics of hibernating yellow-bellied marmots (Marmota flaviventris).
AB  - Yellow-bellied marmots (Rodentia: Sciuridae) typically hibernate for eight
      months. This study explored energetic costs of hibernation in young and adults at
      10 and 6 degrees C. Age significantly affected the percent time torpid, total and
      mass-specific VO(2), use of energy during torpor, and daily mass loss at 6
      degrees C. Thus young had a higher mass-specific VO(2) during a torpor bout,
      which was attributed to higher metabolism during deep torpor. Total VO(2) during
      a bout was higher in young and there were significant temperature/age
      interactions; young had a higher VO(2) during torpor and deep torpor at 6 degrees
      C than at 10 degrees C. VO(2) increased at T(E)s below 6 degrees C. Young had a
      higher daily mass loss than adults at 6 degrees C. Euthermy increased energetic
      costs 19.3 times over those of torpor and 23.5 times over those of deep torpor.
      Energy costs are minimized by spending 88.6% of the hibernation period in torpor,
      by the rapid decline of VO(2) from euthermy to torpor and by allowing T(B) to
      decline at low T(E). Torpidity results in average energy savings during winter of
      83.3% of the costs of maintaining euthermy. Energy savings are greater than those
      reported for Marmota marmota and M. monax.

PMID- 12507614
TI  - Electron microscopic evidence for the thick filament interconnections associated
      with the catch state in the anterior byssal retractor muscle of Mytilus edulis.
AB  - The anterior byssal retractor muscle (ABRM) of a bivalve mollusc Mytilus edulis
      is known to exhibit catch state, i.e. a prolonged tonic contraction maintained
      with very little energy expenditure. Two different hypotheses have been put
      forward concerning the catch state; one assumes actin-myosin linkages between the
      thick and thin filaments that dissociate extremely slowly (linkage hypothesis),
      while the other postulates a load-bearing structure other than actin-myosin
      linkages (parallel hypothesis). We explored the possible load-bearing structure
      responsible for the catch state by examining the arrangement of the thick and
      thin filaments within the ABRM fibers, using techniques of quick freezing and
      freeze substitution. No thick filament aggregation was observed in the cross
      section of the fibers quickly frozen not only in the relaxed and actively
      contracting states but also in the catch state. The thick filaments were,
      however, occasionally interconnected with each other either directly or by
      distinct projections in all the three states studied. The proportion of the
      interconnected thick filaments relative to the total thick filaments in a given
      cross-sectional area was much larger in the catch state than in the relaxed and
      actively contracting states, providing evidence that the thick filament
      interconnection is responsible for the catch state.

PMID- 12507615
TI  - Mineralogy of shells from two freshwater snails Belgrandiella fontinalis and B
      kuesteri.
AB  - X-ray powder diffraction (XRD) was used to study the mineral composition of
      shells of snails Belgrandiella fontinalis and Belgrandiella kuesteri collected
      from three freshwater springs in northeastern Slovenia. The fractions of
      aragonite, calcite, dolomite and quartz in particular shells were determined. The
      analysed shells consisted of two or more distinct inorganic layers. The outer
      shell layer for both species and all sampling localities contained aragonite. The
      outer layer of B. fontinalis collected at one locality, also contained a small
      fraction of calcite ( approximately 1 molar%) besides the dominant aragonite.
      Calcite was identified in the inner layer(s) of both species (2 to 3 molar%),
      while quartz was found only in B. kuesteri (5-7 molar%). However, both species
      sampled at one locality showed the presence of dolomite (approx. 20 molar%) in
      the inner layer(s). The presence of dolomite in the shells of adult gastropods
      and even molluscs is unusual. A possible formation mechanism and specific
      ecological factor that could influence the precipitation of dolomite in the
      shells of different Belgrandiella species is discussed.

PMID- 12507616
TI  - Composition and energy density of eggs from two species of freshwater turtle with
      twofold ranges in egg size.
AB  - Lipid, protein, ash, carbohydrate and water content and energy density of eggs
      were measured from different clutches over a range of egg size in two species of
      freshwater turtle. Dry egg contents consisted of protein (54-60%), lipid (25-31%)
      and ash (5-6%) while carbohydrate was found to be negligible (<1%). Albumen
      consisted principally of water ( approximately 98%), and the dry component was
      composed of protein (47-51%), ash (19-26%) and lipid (18-21%), but contributed
      only a small amount ( approximately 2%) to overall dry egg contents. Energy
      density of dry albumen (15-17 kJ/g) was significantly lower than for dry yolk (26
      27 kJ/g). Yolk consisted of 62-70% water, and the dry component was composed of
      protein (54-61%), lipid (25-31%) and ash (5-6%). Fractional concentrations of
      water, lipid, protein and ash and energy density remained constant over the range
      of egg size in Emydura signata eggs. In contrast, an increase in the yolk to
      albumen ratio and a decrease in water content of yolk as egg size increased
      caused the composition and energy density of Chelodina expansa eggs to vary
      systematically with egg size.

PMID- 12507617
TI  - The influence of heat increment of feeding on basal metabolic rate in Phyllotis
      darwini (Muridae).
AB  - One of the most important prerequisites for obtaining a reliable measure of basal
      metabolic rate (BMR) in endotherms is that the animal must be in a post
      absorptive condition. However, because of the diversity of nutrition and
      digestion modes in vertebrates, it is not simple to generalize a standard
      procedure for BMR measurement. Thus, information in this regard must be
      experimentally obtained by measuring the heat increment of feeding (HIF). We used
      a repeated-measures design to test for the effects of HIF on BMR in Phyllotis
      darwini, a granivorous rodent. Our results suggest that, in this species, feeding
      induces an elevation in O(2) consumption that can persist up to 4 h after the
      last meal. In addition, and irrespective of the fasting period, measures made
      with less than 2 h of fasting yield BMR values that are significantly higher than
      measurements after longer fasting periods (i.e. 3 and 4 h).

PMID- 12507618
TI  - Lipoprotein lipase in lactating and neonatal northern fur seals: exploring
      physiological management of energetic conflicts.
AB  - Otariid lactation and neonatal growth are cyclical processes tied to maternal
      foraging and nursing patterns (i.e. at sea and on land). Both mother and pup
      undergo repeated shifts from a positive to a negative energy balance, the
      physiological mechanisms of which are unclear. We measured plasma and tissue
      lipoprotein lipase (LPL) in free-ranging northern fur seal mother-pup pairs
      throughout the first month of lactation. Plasma LPL levels were similar in
      lactating females (11.3-15.9 U) and growing neonates (8.2-15.2 U). Mammary LPL
      activity was variable, but highest during the attendance period (3.1 U), while
      maternal blubber LPL was consistently low (<0.5 U). Neonatal blubber LPL activity
      was also low (0.2-0.4 U) in accordance with their low growth rates and relatively
      limited blubber deposition.

PMID- 12507619
TI  - Low temperature cardiac response to exhaustive exercise in fish with different
      levels of winter quiescence.
AB  - We examined the cardiac responses of different fish species to anaerobic exercise
      at low temperatures (3 degrees C). Three species of sympatric warmwater fish with
      perceived differences in winter activity were used for this comparative study:
      the winter-quiescent largemouth bass (Micropterus salmoides); the winter-active
      white bass (Morone chrysops); and the intermediately winter-active black crappie
      (Pomoxis nigromaculatus). Perceived differences in winter activity were reflected
      in cardiac responses; e.g. basal cardiac values were lowest for largemouth bass,
      highest for white bass, and intermediate for black crappie. In addition, cardiac
      recovery was most rapid for white bass, slowest for largemouth bass and
      intermediate for black crappie. When disturbed at low temperatures, largemouth
      bass and black crappie elevated cardiac output principally through increases in
      heart rate despite substantial decreases in stroke volume. Conversely, white bass
      principally used stroke volume modulation to change cardiac output. The results
      of this study indicate that different species respond differently to exercise at
      low temperatures. Management strategies should recognize that such variation
      exists and ensure that management decisions are based upon an understanding of
      the low temperature exercise physiology and winter biology of the species of
      interest.

PMID- 12507620
TI  - The physiological response of diploid and triploid brook trout to exhaustive
      exercise.
AB  - Using triploidy as an experimental model, we examined whether cell size limits
      the post-exercise recovery process in fish. Because triploids generally possess
      larger cells, which could affect many physiological and biochemical processes, we
      hypothesized that triploids would take longer to recover from exhaustive exercise
      compared to diploids. To test this, we measured plasma lactate, glucose and
      osmolality, and white muscle energy stores (glycogen, phosphocreatine and ATP)
      and lactate before and immediately following exhaustive exercise and during
      recovery at 2 and 4 h post-exercise. In addition, oxygen consumption and ammonia
      excretion rates were determined before and after exhaustive exercise. Overall,
      diploid and triploid brook trout showed similar metabolic responses exercise, but
      plasma osmolality, white muscle lactate, white muscle ATP and post-exercise
      oxygen consumption rates recovered earlier in triploids compared to diploids. The
      results of this study suggest that the characteristic larger cell size of
      triploidy does not limit the physiological response to, or recovery from,
      exhaustive exercise.

PMID- 12507621
TI  - Gap junctions do not underlie changes in whole-cell conductance in anoxic turtle
      brain.
AB  - An acute reduction in cell membrane permeability could provide an effective
      strategy to prolong anoxic survival. A previous study has shown that in the
      western painted turtle whole-cell neuronal conductance (G(w)) decreases during
      anoxia, which may be mediated by the activation of adenosine A(1) receptors and
      calcium. Reduction in G(w) is thought to be the result of ion channel closure,
      but closure of gap junctions could also be responsible for this phenomenon. In
      our study, antibody staining of connexin 32 and 43 (Cx32 and Cx43) suggested the
      presence of gap junctional components in the turtle cortex. To examine if gap
      junctions were involved in the previously measured anoxic decrease in G(w),
      neuronal connectivity was assessed through the measurement of whole-cell
      capacitance (C(w)). Turtle cortical sheets were perfused with normoxic
      (95%O(2)/5%CO(2)), anoxic (95%N(2)/5%CO(2)), high calcium (4 mM) and adenosine
      (200 microm) artificial cerebral spinal fluid (aCSF). No significant change in
      C(w) was observed under any of the above conditions. However, during hypo-osmotic
      aCSF perfusion C(w) decreased significantly, with the lowest value of 50+/-10.4
      pF (P<0.05) occurring at 30 min. To visualize changes in gap junction
      permeability lucifer yellow was loaded into turtle neurons during normoxic,
      anoxic, 0 calcium, hypo-osmotic, cold shock, (+)-isoproterenol, nitric oxide
      donor S-nitoso-acetyl penicillamine, and 8-bromo-guanosine 3',5'-cyclic
      monophosphate aCSF perfusion. Dye propagation was only observed in 3 of 20 cold
      shock experiments (4 degrees C). We conclude that gap junctions are not involved
      in the acute reduction in G(w) previously observed during anoxia and that our
      results support the hypothesis that ion channel arrest is involved.

PMID- 12507622
TI  - Response of the parotid gland of red kangaroos, Macropus rufus, to phenylephrine
      stimulation.
AB  - Intracarotid infusions of l-phenylephrine at 1.0 or 10 nmol kg(-1) min(-1) were
      accompanied by increases in salivary amylase activity, protein, potassium,
      magnesium and chloride relative to cholinergically-stimulated saliva. Intravenous
      infusions of phenylephrine at the same dose rates had a lesser effect on salivary
      composition particularly protein. Propranolol administered with phenylephrine via
      the carotid artery, at an antagonist/agonist ratio of 10:1, was much more
      effective in blocking the phenylephrine-induced changes in salivary composition
      than equimolar infusion of phentolamine with phenylephrine. It was concluded that
      alpha(1)-adrenoreceptors were not present in functionally significant numbers in
      the gland and that the effect of phenylephrine on the kangaroo parotid was
      mediated by beta-adrenoreceptors. As the phenylephrine dose rates in the
      kangaroos were comparable with those used to determine alpha-adrenergic responses
      of eutherian salivary glands and as phentolamine appeared to have minor beta
      sympathomimetic activity, at least one subtype of beta-adrenoreceptors in
      macropods may not be identical to its eutherian counterpart.

PMID- 12507623
TI  - Cuticular permeability of two species of Coptotermes Wasmann (Isoptera:
      Rhinotermitidae).
AB  - Cuticular permeability (CP) values of worker and soldier castes of Coptotermes
      formosanus Shiraki and Coptotermes vastator Light were determined using
      gravimetric techniques. Comparisons were made between castes, species, and
      between colonies of C. formosanus and C. vastator. CP values did not differ among
      either species or colony, however they did differ between castes. Data reported
      here and that of established data in the literature for C. formosanus are
      inconsistent, with the current report having values as small as half that of
      previously published data. Examining mean CP data by colony indicated that there
      is a range for Coptotermes spp. termites, from 6.84+/-1.2 to 25.61+/-1.49 microg
      H(2)Ocm(-2)mmHg(-1)h(-1) dependent upon caste. A novel method of examining
      intercaste CP variability is the use of worker:soldier CP ratios. Ratios for C.
      formosanus were consistent between the current study and previous reports. Mean
      percentage total body water (%TBW) lost at the time of death was 33.75+/-1.15%
      (soldiers) and 54.24+/-1.43% (workers) for C. formosanus, and 37.69+/-3.31%
      (soldiers) and 52.87+/-3.65% (workers) for C. vastator. Consistently, %TBW (and
      fresh mass) was greater in worker than in soldier castes. These data suggest the
      use of water storage mechanisms in worker termites, as shown for other
      rhinotermitids.

PMID- 12507624
TI  - Foreword: Evaluation of new treatment paradigms for diabetic retinopathy and
      macular edema.

PMID- 12507625
TI  - Changing times for the management of diabetic retinopathy.
AB  - Laser photocoagulation has led a revolution in the management of diabetic
      retinopathy. Scatter photocoagulation and focal photocoagulation has been shown
      to be effective in reducing vision loss. Just as dramatic as laser
      photocoagulation, medical treatment has led another revolution in the treatment
      of diabetic retinopathy. Good glycemic, blood pressure, and lipid control have
      contributed to further reduce vision loss and laser photocoagulation. In the very
      near future, there will be significant advances in pharmacologic treatment of
      diabetic retinopathy. Treatment with antioxidants, agents inhibiting
      hyperglycemia-induced protein kinase activity, and other agents will likely
      prevent the development/progression of retinopathy. Because pharmacologic agents
      are aimed at the prevention of retinopathy, patients with retinopathy will need
      to be examined earlier to diagnose retinopathy at earlier stages. To maximize the
      opportunity for earlier diagnosis, ophthalmologist may need to adopt screening
      strategies to identify patients most likely to benefit from these new treatments.

PMID- 12507626
TI  - Prevention of visual loss from diabetic retinopathy.
AB  - Despite the results of clinical trials showing the efficacy of panretinal and
      focal photocoagulation of proliferative retinopathy with high-risk
      characteristics for severe visual loss and for clinically significant macular
      edema, retinopathy remains an important cause of visual loss. Because these
      treatments are associated with cost, may not always prevent visual loss, and may
      result in complications, other nonsurgical interventions have been sought to
      prevent visual loss from retinopathy. Data from epidemiological studies showed an
      association between hyperglycemia, hypertension, and dyslipidemia and the
      incidence and progression of retinopathy and macular edema in people with
      diabetes. These findings resulted in a number of clinical trials that have shown
      the efficacy of intensive control of hyperglycemia and hypertension in reducing
      the incidence and progression of diabetic retinopathy. Despite these findings,
      the majority of persons with diabetes fail to achieve American Diabetes
      Association-targeted guidelines for glycosylated hemoglobin, blood pressure, and
      lipid levels. Thus, new approaches for achieving normalization of blood glucose
      levels are needed and new clinical trials are underway to assess these new
      interventions.

PMID- 12507627
TI  - Diabetic retinopathy: more than meets the eye.
AB  - Retinal microvascular dysfunction in diabetes is a major component of diabetic
      retinopathy. This review highlights recent observations regarding the cellular
      anatomy that contributes to the blood-retinal barrier and its breakdown, the
      alterations of macroglial, neuronal, and microglial cells in diabetes, and how
      these changes lead to loss of vision. In addition, the effects of systemic
      pathophysiologic influences, including metabolic control, blood pressure, and
      fluid volume on the formation of diabetic macular edema are discussed. Finally,
      an overview of inflammatory mechanisms and responses in the retina in diabetes is
      provided. Together, these new observations provide a broader clinical and
      research perspective on diabetic retinal vascular dysfunction than previously
      considered, and provide new avenues for improved treatments to prevent loss of
      vision.

PMID- 12507628
TI  - The potential role of PKC beta in diabetic retinopathy and macular edema.
AB  - Diabetic retinopathy is one of the most debilitating complications of diabetes
      mellitus. Despite major advances in understanding the pathogenesis of this
      disease and the efficacy of current therapies, diabetic retinopathy remains the
      leading cause of new-onset blindness among working-age people. The mainstay of
      current therapy, laser photocoagulation, is useful in preventing blindness and
      severe vision loss but is not often effective in restoring lost visual acuity. In
      addition, troublesome side effects and potentially serious complications may
      occur. Diabetic retinopathy is characterized by a progression of abnormalities.
      Nonproliferative retinopathy results from a series of biochemical and cellular
      changes that ultimately cause progressive retinal ischemia. The subsequent
      elaboration of growth factors in response to ischemia leads to the development of
      proliferative retinopathy, which is characterized by aberrant neovacularization
      of the retina-potentially leading to severe, irreversible visual loss. Increased
      retinal vascular leakage may also occur at any stage in this process, resulting
      in macular edema and possible progressive visual impairment. Although numerous
      biochemical factors are thought to play a role in the development of retinopathy,
      activation of protein kinase C (PKC), specifically the beta isoform of PKC (PKC
      beta), is implicated for both the early and late-stage manifestations of
      retinopathy. Studies suggest that orally administered LY333531, a beta-isoform
      specific PKC inhibitor, may be effective in ameliorating retinopathy progression,
      proliferation, and retinal vascular leakage. The status of ongoing clinical
      trials aimed at addressing the efficacy of PKC beta with regard to diabetes
      induced retinal complications and perspectives on the role of PKC beta are
      presented.

PMID- 12507629
TI  - Mechanisms for monitoring changes in retinal status following therapeutic
      intervention in diabetic retinopathy.
AB  - Trials of new compounds (e.g., protein kinase C inhibitors) for the treatment of
      diabetic retinopathy and diabetic macular edema historically have used tools such
      as seven-field stereoscopic fundus photography to grade retinopathy, and
      endpoints such as the need for retinal photocoagulation to evaluate efficacy.
      Improvements in diabetes care have led to slower spontaneous progression of
      retinopathy than anticipated, however. A consequence of this trend is that
      clinical trials for diabetic retinopathy and diabetic macular edema are expected
      to last for many years and require large numbers of patients before evidence
      based conclusions can be made. Therefore, interest in new assessment tools is
      growing. This review briefly describes the basic pathophysiologic factors
      involved in the pathogenesis of diabetic macular edema to provide a basis for the
      introduction of new quantitative and objective endpoints. Special consideration
      is given to measuring fluorescein permeability of the blood-retinal barrier. The
      quantitative measurement of retinal thickness using optical coherence tomography
      is a promising noninvasive method. Microaneurysm counts, assessment of length and
      diameter of retinal vessels, and computerized quantification of all pathologic
      elements may also be useful as diagnostic tools and/or efficacy endpoints.

PMID- 12507630
TI  - Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock
      protein 72 in human peripheral blood mononuclear cells.
AB  - OBJECTIVE: Overexpression of pro-inflammatory cytokines such as tumor necrosis
      factor-alpha (TNF-alpha) can contribute to multiple organ dysfunction syndrome
      and septic shock in critically ill patients. We previously found that glutamine
      (GLN) can attenuate cytokine expression, induce heat shock protein 72 (HSP 72),
      and protect against endotoxin-induced mortality and organ injury in an in vivo
      rat model. However, data on the effect of GLN on direct attenuation of cytokine
      release and HSP 72 expression in human peripheral blood polymorphonuclear cells
      (PBMCs) is lacking. METHODS: In this study, we assessed the effect of GLN on TNF
      alpha and HSP 72 expression in human PBMCs. After treating with various doses of
      GLN, human PBMCs were stimulated with lipopolysaccharide (LPS). TNF-alpha release
      was analyzed via enzyme-linked immunosorbent assay and HSP 72 via western blot.
      RESULTS: GLN at doses greater than 4 mM decreased TNF-alpha release at 4 and 24 h
      after LPS stimulation. Sublethal heating of PBMCs before LPS also markedly
      decreased TNF-alpha after LPS. Doses of GLN greater than 2 to 4 mM led to an
      increase in HSP 72 expression after LPS. CONCLUSION: These results indicate that
      GLN, which may improve outcomes in critically ill patients, can directly
      attenuate pro-inflammatory cytokine release in PBMCs. This effect may be related
      to enhanced HSP 72 expression.

PMID- 12507631
TI  - Characterization of meat consumption and risk of colorectal cancer in Cordoba,
      Argentina.
AB  - BACKGROUND: The Argentinean food pattern, rich in beef and fats and poor in
      fibers, may be related to an risk of increased colorectal cancer (CRC). To
      examine the relation between CRC risk and meat type, we carried out a case
      control study in Cordoba, Argentina. METHODS: We interviewed 287 patients with
      colorectal adenocarcinomas and 566 control subjects admitted to the largest
      hospitals in greater Cordoba. Dietary habits were assessed by a food-frequency
      questionnaire, and different meat types were evaluated. Regression analyses
      determined the contribution of meat to total energy and macronutrients.
      Unconditional multiple logistic regression was performed to calculate odds ratios
      (ORs) and 95% confidence intervals (CIs). RESULTS: Median intake of all meats,
      predominantly bovine, was high, reaching almost 300 g/d in men. Meats provided
      approximately 50% of total energy intake and 64% to 67% of total protein.
      Patients obtained significantly more cholesterol and total lipids from meats than
      did controls. Consumption of total meat, red meat, and other types of meat were
      not related to increased risk of CRC. However, an increased risk of CRC was found
      for those consuming relatively large amounts of cold cuts and sausages (OR, 1.47;
      CI, 1.02-2.15) and bovine viscera (OR, 1.73; CI, 1.18-2.54). Lean beef was
      associated with a decreased risk of CRC at the second (OR, 0.64; CI, 0.43-0.94)
      and third (OR, 0.67; CI, 0.40-0.97) tertiles. CONCLUSIONS: Red meat produced a
      different pattern of risk according to its fat content. Further studies should
      assess the possible role of cooking meat and other non-nutritional components.

PMID- 12507632
TI  - Lower serum levels of beta-carotene in Lithuanian men are accompanied by higher
      urinary excretion of the oxidative DNA adduct, 8-hydroxydeoxyguanosine. The
      LiVicordia study.
AB  - OBJECTIVE: In 1995, middle-aged Lithuanian men had a four-fold higher risk than
      Swedish men of dying from coronary heart disease. The cross-sectional LiVicordia
      study had reported significantly lower levels of the lipid-soluble antioxidants
      lycopene, beta-carotene, and gamma-tocopherol among Lithuanian men than among
      Swedish men. We examined whether there were differences in urinary 8
      hydroxydeoxyguanosine (8OHdG), a marker of oxidative stress, between these groups
      of men. METHODS: Using automated coupled column high-performance liquid
      chromatography with electrochemical detection, we examined 50-y-old men randomly
      sampled from Linkoping, Sweden (n = 99) and Vilnius, Lithuania (n = 109) with
      regard to urinary concentrations of 8-OHdG. RESULTS: Levels of 8-OHdG were higher
      in the Lithuanian men than in the Swedish men (20.9 +/- 0.91 versus 14.9 +/- 0.75
      nM/L, P < 0.001), and this difference was evident in smokers (P < 0.01) and non
      smokers (P < 0.001). Serum levels of alpha- and beta-carotene were inversely
      correlated to urinary 8-OHdG levels (P < 0.05 in both cases). Habitual smoking
      and low levels of beta-carotene contributed significantly to higher oxidative DNA
      damage expressed as urinary 8-OHdG. CONCLUSIONS: These findings indicate that
      increased urinary 8-OHdG levels accompany lower serum levels of antioxidants in
      Lithuanian men. They supported previous suggestions that increased oxidative
      stress may be one factor behind the higher mortality in Lithuanian men.

PMID- 12507633
TI  - Determination of total potentially available nucleosides in human milk from Asian
      women.
AB  - OBJECTIVE: The objective was to measure the total potentially available
      nucleosides (TPAN) in breast milk from Asian women. METHODS: One hundred sixty
      milk samples were collected from 135 healthy, lactating women in Hong Kong, the
      Philippines, and Singapore at four stages of lactation: colostrum (1 to 3 days
      postpartum), transitional (7 to 10 days postpartum), early mature (28 to 35 days
      postpartum), and late mature (90 to 100 days postpartum). Samples were pooled by
      site and stage of lactation before analysis. RESULTS: The mean TPAN concentration
      was 203 microM/L (69.4 mg/L corrected for recovery). Average TPAN concentrations
      were 171.9 microM/L in colostrum, 208.1 microM/L in transitional milk, 221.6
      microM/L in early mature milk, and 210.6 microM/L in late mature milk, with no
      notable differences between countries. The major sources of nucleosides were RNA
      (43.3% of TPAN) and free nucleotides (39.9% of TPAN). The average percentages of
      cytidine, uridine, guanosine, and adenosine monophosphates were 44.5%, 23.1%,
      16.5%, and 16.1% of TPAN, respectively. The sources of nucleosides and
      percentages of nucleotide bases were similar for all stages of lactation. Over
      91% of the TPAN was present in the non-cellular component except in colostrum.
      CONCLUSIONS: The average TPAN level in Asian women is similar to that in European
      and American women, and free nucleotides in human milk represent less than half
      of the TPAN.

PMID- 12507634
TI  - Lutein, but not alpha-tocopherol, supplementation improves visual function in
      patients with age-related cataracts: a 2-y double-blind, placebo-controlled pilot
      study.
AB  - OBJECTIVE: We investigated the effect of long-term antioxidant supplementation
      (lutein and alpha-tocopherol) on serum levels and visual performance in patients
      with cataracts. METHODS: Seventeen patients clinically diagnosed with age-related
      cataracts were randomized in a double-blind study involving dietary
      supplementation with lutein (15 mg; n = 5), alpha-tocopherol (100 mg; n = 6), or
      placebo (n = 6), three times a week for up to 2 y. Serum carotenoid and
      tocopherol concentrations were determined with quality-controlled high
      performance liquid chromatography, and visual performance (visual acuity and
      glare sensitivity) and biochemical and hematologic indexes were monitored every 3
      mo throughout the study. Changes in these parameters were assessed by General
      Linear Model (GLM) repeated measures analysis. RESULTS: Serum concentrations of
      lutein and alpha-tocopherol increased with supplementation, although statistical
      significance was reached only in the lutein group. Visual performance (visual
      acuity and glare sensitivity) improved in the lutein group, whereas there was a
      trend toward the maintenance of and decrease in visual acuity with alpha
      tocopherol and placebo supplementation, respectively. No significant side effects
      or changes in biochemical or hematologic profiles were observed in any of the
      subjects during the study. CONCLUSIONS: Visual function in patients with age
      related cataracts who received the lutein supplements improved, suggesting that a
      higher intake of lutein, through lutein-rich fruit and vegetables or supplements,
      may have beneficial effects on the visual performance of people with age-related
      cataracts.

PMID- 12507635
TI  - Thermogenesis induced by a high-carbohydrate meal in fasted lean and overweight
      young men: insulin, body fat, and sympathetic nervous system involvement.
AB  - OBJECTIVE: This dietary trial was designed to evaluate the effect of an
      experimental short-term fasting period followed by a high-carbohydrate meal on
      energy expenditure, thermogenesis, and sympathetic nervous system activity in
      normal (body mass index < 25 kg/m(2)) and overweight (body mass index > 27
      kg/m(2)) men who were healthy, non-diabetic or with no other endocrine disease,
      non-smokers, not taking oral prescription medications, and with a stable body
      weight for the previous 3 mo. METHODS: Fasting and fed energy expenditures and
      diet-induced thermogenesis were measured after a high-carbohydrate meal in seven
      overweight and six lean young male subjects by indirect calorimetry. Heart rate,
      urinary excretion of catecholamines, serum glucose, and insulin were also
      measured over the experimental fasting (7.5 h) and postprandial (4 h) periods.
      RESULTS: After carbohydrate intake, overweight men showed a significantly higher
      energy production (kJ/kg of fat-free mass) than did lean individuals, and the
      diet-induced thermogenesis (percentage of energy intake) was positively
      correlated with body fat (kg), percentage of body fat, fat-free mass (kg), and
      fasting pre-meal serum insulin levels. Postprandial cumulative energy expenditure
      was directly associated with postprandial insulin response and with mean
      postprandial heart rate values. No significant differences in urinary
      catecholamines were found between lean and overweight men at basal conditions or
      during the study period. CONCLUSIONS: Overweight individuals showed similar short
      term sympathetic nervous system responses induced by an experimental fasting
      period. Although diet-induced thermogenesis after carbohydrate intake was not
      statistically different between lean and overweight men, the postprandial insulin
      response and body fat content seemed to be involved in sympathetic nervous system
      activity.

PMID- 12507636
TI  - Modulation of body fat and serum leptin levels by dietary conjugated linoleic
      acid in Sprague-Dawley rats fed various fat-level diets.
AB  - OBJECTIVES: In this study, we examined the effect of dietary conjugated linoleic
      acid (CLA) on body fat levels in Sprague-Dawley rats. METHODS: Rats were fed AIN
      93G type diets containing 4%, 7%, and 10% fats with or without 1.5% CLA. RESULTS:
      Three weeks after the onset of the experimental period, the weights of perirenal
      white adipose tissue were lower in CLA-fed rats. The weights of epididymal white
      adipose tissue also were lower in CLA-fed rats than in control rats, but this
      effect disappeared with increased dietary fat level. Serum leptin levels tended
      to be lower in the CLA group, especially the low-fat diet group, than in the
      control group. There were significant positive correlations between serum leptin
      level and weights of perirenal and epididymal white adipose tissues in control
      groups, but these correlations were weaker in the CLA groups. Serum tumor
      necrosis factor-alpha levels also tended to be lower in CLA-fed rats, and this
      tendency was most remarkable in the rats fed 7% fat diets. CONCLUSION: In
      conclusion, dietary CLA, especially the low-fat diet, reduced body fat without
      hepatic injury to Sprague-Dawley rats.

PMID- 12507637
TI  - Integration of orosensory and postingestive stimuli for the control of excessive
      fat intake in mice.
AB  - OBJECTIVES: Long-term preferences for, and reinforcement effects of, undigested
      fat substitutes were investigated by means of a two-bottle choice test and the
      conditioned place preference (CPP) test. METHODS: We tested intact corn oil and
      sorbitol fatty acid esters, which have been developed as non-digestible fat
      substitutes with low energy (1.5 kcal/g). RESULTS: Palatability of the sorbitol
      fatty acid esters was similar to corn oil over 30 min in the short-term two
      bottle choice test in mice. However, mice did not continue to eat the fat
      substitute in the long-term two-bottle choice test, which included postprandial
      feedback effects. Moreover, sorbitol fatty acid ester did not act as a reinforcer
      in the CPP test. Mice with 0.1 mL of corn oil placed into their stomachs just
      before conditioning showed reinforcing effects on taking sorbitol fatty acid
      ester in the CPP test. However, intragastric administration of corn oil alone
      without stimulation of the oral cavity did not show any such reinforcing effects
      against corn oil. CONCLUSIONS: These results suggest that the postingestible
      effects of corn oil are involved in long-term preference and reinforcing effects.

PMID- 12507638
TI  - Dietary ribonucleotides increase antigen-specific type 1 T-helper cells in the
      regional draining lymph nodes in young BALB/cJ mice.
AB  - OBJECTIVES: We assessed the mechanisms of ribonucleotide action on type 1 T
      helper cell (Th1) responses against ovalbumin (OVA) in Th2-biased BALB/cJ mice.
      METHODS: Mice were fed a ribonucleotide-free or ribonucleotide-supplemented diet
      and given OVA subcutaneously with incomplete Freund's adjuvant at 3 and 6 wk.
      Costimulatory molecule expression (CD86 and CD154), the state of naive versus
      effecter/memory Th cells, and the frequency of OVA-specific resting versus
      activated Th1/Th2 cells were accessed in cells from the regional draining lymph
      nodes. OVA challenge increased CD86, but not CD154, expression. Effector/memory
      stage Th/cytotoxic T cells increased after the first and second OVA challenges.
      RESULTS: Dietary ribonucleotides did not affect the expression of any of these
      cell surface molecules. Antigen-specific Th1 and Th2 cells increased 10 d after
      the first OVA dose and 5 d after the second OVA dose. Further, dietary
      ribonucleotides increased OVA-specific resting and activated Th1 cells 10 d after
      the first OVA dose and decreased OVA-specific resting Th2 cells 5 d after the
      second OVA dose. CONCLUSIONS: Dietary ribonucleotides may attenuate skewed Th2
      responses by augmenting clonal expansion of OVA-specific Th1 cells, suppressing
      expansion of OVA-specific Th2 cells in Th2-biased BLAB/cJ mice, and not affecting
      antigen non-specific cell surface markers.

PMID- 12507639
TI  - Lack of effects by tricyclic antidepressant and serotonin inhibitors on anorexia
      in MCG 101 tumor-bearing mice with eicosanoid-related cachexia.
AB  - OBJECTIVES: Anorexia is a major clinical problem in large number of patients with
      advanced cancer disease. Serotonergic mechanisms are assumed to play a role in
      the process of feeding behavior during normal and pathologic circumstances, which
      may also involve cancer anorexia according to previous experimental and clinical
      studies. METHODS: In the present study, we evaluated the effect of the tricyclic
      antidepressants desipramine (7.5 mg x kg(-1) x d(-1), intraperitoneal) and
      imipramine (2 to 5 mg. kg(-1) x d(-1), intraperitoneal) the serotonin synthesis
      inhibitor para-chlorophenylalanine (300 mg x kg(-1) x d(-1), intraperitoneal),
      the serotonin receptor 5-HT(2C) antagonist cyproheptadine (5 mg x kg(-1) x d(-1),
      intraperitoneal) and the selective serotonin reuptake inhibitor citalopram (20 mg
      x kg(-1) x d(-1), intraperitoneal) on anorexia in MCG-101 tumor-bearing mice, a
      model with significant anorexia and cachexia sensitive to cyclooxygenase
      inhibition. Also, MCG 101-bearing mice develop well-recognized alterations in
      brain tryptophan/serotonin metabolism as increased Trp, 5-HPT, and 5-HIAA during
      tumor progression. RESULTS: Daily provision of desipramine, imipramine, para
      chloropheylalanine, cyproheptadine, and citalopram at doses that cause behavioral
      and metabolic alterations in normal mice did not alter food intake or body weight
      in tumor-bearing and healthy control mice. Also, the treatments did not decrease
      elevated plasma concentrations of interleukin-6 and prostaglandin E(2) in the
      tumor-bearing mice. CONCLUSIONS: Thus, our results do not support previous
      observations that serotonin metabolism itself is a major factor behind anorexia
      in tumor-bearing animals in general. Rather, other mechanisms, such as eicosanoid
      and nitric oxide-dependent pathways, seem to be more important for induction of
      anorexia along tumor progression in the present model.

PMID- 12507640
TI  - Sulfur: its clinical and toxicologic aspects.
AB  - Although there is no known dietary requirement for inorganic sulfur, it is an
      essential element for all animal species in as much as they all require the
      sulfur-containing amino acid methionine. There are three predominate forms of
      organic sulfur in animals and humans: 1). the thiomethyl of methionine residues
      in protein; 2). the sulfhydryl disulfides of protein; and 3). the compounds
      containing ester or amide bound sulfates of glycosaminoglycans, steroids, and
      many xenobiotic metabolites. Thus, sulfur becomes an important constituent of
      amino acids, proteins, enzymes, vitamins and other biomolecules. Unlike mammalian
      species, plants can use inorganic sulfur and synthesize methionine from which are
      synthesized all the other important sulfur compounds. Hence, sulfur deficiency
      occurs mainly when plants are grown in sulfur-depleted soils and when humans and
      animals consume low-protein diets. In recent times, however, the increasing
      prevalence of refining petroleum and smelting sulfur compounds of metallic
      minerals into free metals are having a large impact on the balance of sulfur in
      the environment. Sulfur toxicity is associated mainly with high levels of the
      element and its toxic volatile substances in the environment. Sulfur dioxide
      (SO(2)), a major air pollutant, may adversely affect animal and human health by
      causing bronchitis, bronchoconstriction, and increased pulmonary resistance.

PMID- 12507641
TI  - Long-chain polyunsaturated fatty acids in the growth and development of the brain
      and memory.

PMID- 12507642
TI  - Long-chain polyunsaturated fatty acids essential for brain growth and
      development.

PMID- 12507643
TI  - Orosensory and postingestive stimuli for the control of food intake.

PMID- 12507644
TI  - Pathogenesis of cancer anorexia: still doubts after all these years?

PMID- 12507645
TI  - Dietary ribonucleotides and health.

PMID- 12507646
TI  - Establishment of an intestinal rehabilitation program in an international
      tertiary care center.

PMID- 12507647
TI  - Use of ornithine alpha-ketoglutarate in clinical nutrition of elderly patients.

PMID- 12507648
TI  - Stimulant treatment of bulimia nervosa with and without attention-deficit
      disorder: three case reports.

PMID- 12507649
TI  - Benefits from artificial nutritional support: a testimonial.

PMID- 12507651
TI  - Nutritional Endocrinology. New York, New York, USA, March 3, 2002.

PMID- 12507652
TI  - Results important but inconclusive.

PMID- 12507653
TI  - Effects of acrylamide on rodent reproductive performance.
AB  - Acrylamide monomer causes peripheral neurotoxicity, mutagenicity, clastogenicity,
      male reproductive toxicity, prenatal lethality, and endocrine-related tumors in
      rodents. Acrylamide (and/or its metabolite glycidamide) binds to dopamine
      receptors and spermatid protamines and inhibits activity of kinesin and dyneine,
      resulting in interference with neuronal intracellular transport and sperm
      motility. Glycidamide binds to various proteins and DNA. Acrylamide at low doses
      decreases litter size, with rats more sensitive than mice. At higher doses, sperm
      morphology and motility and neurotoxicity are affected, which decreases mating
      frequency. Acrylamide does not affect female reproduction (females exhibit
      neurotoxicity). Dominant lethal mutations cause decreased newborn litter size.
      The mechanisms of action appear to be: (1) acrylamide/glycidamide binding to
      spermatid protamines, causing dominant lethality and effects on sperm morphology;
      and (2) acrylamide binding to motor proteins, causing distal axonopathy,
      including hindlimb weakness/paresis, and effects on mounting, sperm motility, and
      intromission. Glycidamide-induced mutations appear to play no role in
      reproductive or neurologic toxicity.

PMID- 12507654
TI  - Effects of Aroclors and individual PCB congeners on activation of the human
      androgen receptor in vitro.
AB  - To investigate possible interactions between the human androgen receptor and PCBs
      in vitro, we have used a previously characterized human androgen receptor
      reporter gene assay in which PC-3 LUC(AR+) cells respond to 5alpha
      dihydrotestosterone (DHT, 50 pM) with enhanced luciferase activity. The effects
      of Aroclors, commercial mixtures of PCBs, or polychlorinated terphenyls (PCTs)
      (0, 0.1, 1.0, and 10.0 microM) on luciferase activity in PC-3 LUC(AR+) cells were
      determined after exposure for 18 h in the presence and absence of DHT (50 pM). In
      the absence of DHT, none of the Aroclors induced luciferase activity but, in the
      presence of DHT (50 pM), Aroclors 1016, 1221, 1232, 1242, 1248, 1254, 1260, 5432,
      and 5442 acted antagonistically at concentrations that did not affect cell
      viability. Aroclor 5460 was without effect. Similarly, when PCBs found as human
      milk contaminants were assessed as individual congeners (each at 1 microM, where
      no cytotoxic effects were observed), none activated luciferase expression in the
      absence of DHT but PCBs 49, 66, 74, 105, and 118 completely antagonized the
      stimulation by DHT (50 pM) and PCBs 138, 153, and 156 were less effective
      antagonists, reducing the DHT stimulation by about 50%. Thus, 30% (by weight) of
      the PCBs in human milk are androgen antagonists (PCBs 66, 74, 105, and 118) and a
      further 25% are partial antagonists (PCBs 138, 153, and 156). A proportionally
      representative mixture of PCBs that contaminate human milk also caused the DHT
      mediated activation of luciferase activity in PC-3 LUC(AR+) cells to be reduced
      by more than 50%.

PMID- 12507655
TI  - Long-lasting effects of lindane on mouse spermatogenesis induced by in utero
      exposure.
AB  - Long-lasting effects on mouse spermatogenesis induced by prenatal exposure to the
      insecticide lindane have been investigated by conventional reproductive endpoints
      complemented by the flow cytometric (FCM) DNA content analysis of testis cells
      and by the Sperm Chromatin Structure Assay (SCSA). Two lindane dose levels, 15
      and 25 mg/kg bw, and diethylstilboestrol (DES, 10 microg/kg bw) as positive
      control, were administered daily by gavage to pregnant CD1 mice on gestation days
      (GD) 9-16. Reproductive endpoints were evaluated on F1 male mice on postnatal day
      (PND) 60; additionally, animals treated with lindane 25 mg/kg per day and DES
      were examined on PND 100 to evaluate the possible reversibility of the effects.
      On PND 60, lindane and DES caused a reduction in the sperm head count and
      concentration, with recovery in older lindane 25 mg/kg per day animals (PND 100).
      By contrast, the DES group exhibited a greater reduction in the sperm head count
      on PND 100 than on PND 60. Changes in biochemical parameters in the testes,
      lactate dehydrogenase-C(4) (LDH-C(4)), and sorbitol dehydrogenase (SDH)
      activities, were also observed in adult treated F1 mice. Furthermore on PND 60,
      the FCM analysis revealed changes in the pattern of testicular germ cell
      distribution, especially in the haploid subcompartment, in the lindane 25 mg/kg
      per day group. A dose-dependent increase in chromatin abnormalities of the
      epididymal sperm was also shown by SCSA. These changes recovered on PND 100.
      Preliminary qualitative examination did not reveal any significant difference in
      the structure of testicular tissue; however, there were suggestions of a moderate
      increase in number and size of Leydig cells in both DES- and lindane-treated
      animals. The partial reversibility of these effects and the lack of structural
      modification of the testicular tissue as evidenced by histopathologic assessment
      suggest a functional impairment of sperm production and maturation, possibly
      associated with changes induced by lindane on factors affecting intratesticular
      steroidogenesis.

PMID- 12507656
TI  - Antispermatogenic and antifertility effects of 20,25-diazacholesterol
      dihydrochloride in mice.
AB  - The effect of intraperitoneal administration for 28 days of 10, 20, and 30 mg/kg
      body weight per day of 20,25-diazacholesterol dihydrochloride (SC 12937), a
      hypocholesterolemic agent, on the testis of Parkes (P) strain mice was
      investigated. Histologically, testes in mice treated with 10 or 20 mg/kg body
      weight of SC 12937 showed non-uniform degenerative changes in the seminiferous
      tubules as both affected and normal tubules were observed in the same section;
      the affected tubules showed intraepithelial vacuolation, occurrence of giant
      cells, exfoliation of germ cells, and marginal condensation of chromatin in round
      spermatids. In both dosage groups, only 11-12% of the seminiferous tubules were
      affected, and no significant differences were found in the frequency of affected
      tubules between the two groups. By contrast, testes in mice treated with 30 mg/kg
      body weight of the drug exhibited a degenerated appearance of germ cells in all
      seminiferous tubules. The treatment also had adverse effects on motility,
      viability, morphology, and number of spermatozoa in the cauda epididymidis, and
      on fertility. Even 56 days after drug withdrawal, the above parameters remained
      markedly affected. Our results thus suggest that SC 12937 treatment causes
      antispermatogenic and antifertility effects in P mice and that the effects are
      not reversible up to 56 days after drug withdrawal. This compound may prove
      useful in the control of rodent populations.

PMID- 12507657
TI  - A comprehensive evaluation of the reproductive toxicity of Quassia amara in male
      rats.
AB  - Chloroform extracts of the bark of Quassia amara in different dilutions was used
      to assess its impact on the male reproductive system of albino rats. Single daily
      intramuscular injections of the extract for 15 days resulted in a significant
      reduction in the weight of testis and epididymis but not that of the seminal
      vesicles and prostate (all lobes). A marked decrease in the sperm count,
      motility, viability was also observed in sperm collected from the cauda
      epididymis of treated animals. A number of abnormalities like double heads,
      double tails, detached heads and fragile tails were frequently seen. Epididymal
      alpha-glucosidase activity was drastically reduced. However, prostatic acid
      phosphatase activity and citric acid levels and seminal vesicle fructose
      concentrations remained unchanged following treatment. Thus, it appears that the
      prime site of action is at the level of both the testis and the epididymis.
      Examination of the blood showed that cell counts and hemoglobin levels were in
      the normal range. Bilirubin, SGPT, SGOT, protein and urea were also not altered
      by the herbal extract. From the selective action on the male reproductive tract
      we suggest that the chloroform extract of the bark of Quassia amara has potential
      for use as an antifertility agent.

PMID- 12507658
TI  - Intrauterine growth retardation and lack of teratogenic effects of prenatal
      exposure to the combination of paracetamol and caffeine in Wistar rats.
AB  - The effect of the mixture of paracetamol and caffeine on prenatal development in
      rats was studied. Paracetamol:caffeine was prepared with a 5:1 ratio (w/w)
      between compounds and administered orally in Tween-80 water suspension once a day
      to pregnant Wistar rats on gestation days 8 through 14 (plug = day 1). The low
      dose was similar to the preparation available over-the-counter (OTC), 3.5 mg/kg
      of paracetamol and 0.7 mg/kg of caffeine. The middle dose was 35.0 and 7.0 mg/kg,
      and the high dose 350.0 and 70.0 mg/kg for paracetamol and caffeine,
      respectively. On gestation day 21, fetuses were delivered by laparotomy. Corpora
      lutea, fetuses, and number of implantation sites were counted. Live fetuses were
      examined for external, visceral, and skeletal malformations. There was a
      significant decrease in maternal body weight gain and liver weight in all drug
      treated groups and reduced kidney weights in the middle and high dose groups.
      Dose-dependent effects in the middle and high dose groups on fetal body
      weight/growth and placental weight were found. In none of the three dose groups
      was there an increase in external or internal congenital malformations.

PMID- 12507659
TI  - Oocyte number in newborn mice after prenatal octylphenol exposure.
AB  - The aim of the present study was to investigate whether prenatal exposure to the
      suspected estrogenic compound 4-tert-octylphenol (OP), influences oocyte number
      in newborn female mice. In addition, effects on the percentage distribution of
      prefollicular, follicular, and atretic oocytes were investigated. Pregnant mice
      were subcutaneously injected with OP (1 or 250 mg/kg) or vehicle alone on
      embryonic day 11.5-16.5 (plug = embryonic day 0.5). As a positive control for
      estrogenic effects, a group of animals was injected with the synthetic estrogen
      diethylstilbestrol (DES, 100 microg/kg). Ovaries from the offspring were
      collected on the day of birth and a stereologic method, the optical fractionator,
      was used to estimate the number of prefollicular, follicular, and atretic oocytes
      in the ovaries. The total number of oocytes was calculated as the sum of the
      three subpopulation estimates. Neither OP nor DES exposure could be observed to
      affect the total number of oocytes or the percentage distribution of atretic,
      prefollicular, and follicular oocytes. Thus, prenatal OP exposure does not appear
      to cause a serious threat to fetal female germ cell proliferation and survival,
      or early follicle formation.

PMID- 12507660
TI  - Assessment of the perinatal effects of maternal ingestion of Solanum malacoxylon
      in rats.
AB  - A perinatal study was performed to verify the toxic effects of Solanum
      malacoxylon, which contains a glycoside conjugated to Vitamin D(3). In the
      gestational study, female rats received S. malacoxylon leaves in the diet at 0,
      0.1, 0.2, 0.5, and 1% from days 6 to 21 of pregnancy. At 21 days of gestation,
      blood samples were taken from the dams for evaluation of serum Ca and P. A
      laparotomy was performed and the rats were examined for standard parameters of
      reproductive performance. Fetuses were examined for skeletal changes and
      histopathologic evaluation. In the second trial, dams were fed diets containing 0
      or 0.1% S. malacoxylon leaves during the gestation and lactation periods. After
      weaning, all animals were euthanized and biochemical and histopathologic
      evaluations were performed. The biochemical evaluation showed increase in Ca and
      P levels in females from all experimental groups; however, this effect did not
      occurred in a dose-related manner. Pups from dams exposed during gestation and
      lactationi also showed increased Ca and P levels. Fetal data suggested a delay of
      fetal development manifested by decreased body weight and skeletal alterations.
      There was also a reduction in live fetuses. Histopathologic study revealed
      alterations of the soft tissue in litters from dams given 1% dietary S.
      malacoxylon during pregnancy and 0.1% during pregnancy and lactation. These
      findings support our hypothesis that Vitamin D(3) glycoside crosses the placenta
      and suggests milk transfer of this substance.

PMID- 12507661
TI  - Effects of advanced maternal age on development of preimplantation mouse embryos
      obtained from delayed mating.
AB  - Rodent embryos resulting from delayed mating grow more quickly than those
      resulting from normal mating. To clarify the effects of maternal age on this
      enhanced growth and rapid differentiation of mouse embryos obtained from delayed
      mating, we studied normal (0 h after ovulation) and delayed mating (6 h after
      ovulation) subgroups in two different age groups (middle-aged, 9-11 months;
      elderly, 13-15 months), and compared the number of cells and the proportion of
      blastocyst formed (morphologically advanced blastocysts) among them. In middle
      aged female mice, preimplantation embryos derived from delayed mating progressed
      more rapidly than their normally mated counterparts. The number of cells and the
      proportion of blastocyst formed among embryos from delayed mating were almost 3 h
      ahead of those of normal embryos. In the delayed mating subgroup from elderly
      mice, an enhanced rate of development was not observed. There was no difference
      in development of normally mated embryos from middle-aged females compared to
      each counterpart from elderly female mice. Preimplantation mouse embryonic
      development from delayed mating may be affected by advanced maternal age.

PMID- 12507662
TI  - Preimplantation mouse embryo development as a target of the pesticide
      methoxychlor.
AB  - Effects of methoxychlor (MXC) and estradiol-17beta (E) were studied in mouse
      preimplantation embryos. Pregnant mice received s.c. injections of sesame oil
      only, 10 microg E, or 0.5 mg purified (95%) MXC on Days 2-4 of pregnancy (plug =
      Day 1). Another group received a single dose of 2.5 microg E on Day 2 only. Based
      on the average weight of pregnant females, 10 microg of estradiol was equivalent
      to 0.33 mg/kg of bw, 2.5 microg of estradiol was equivalent to 0.082 mg/kg of bw,
      and the 0.5-mg dose of MXC was equivalent to 16.5 mg/kg of bw. All embryos were
      collected for analyses on Day 4. MXC and both estradiol-17beta doses suppressed
      embryonic development to blastocyst, decreased embryo cell numbers, and caused
      abnormal blastocyst formation. The high estradiol-17beta dose significantly
      increased the percent degenerating embryos and caused a tube-locking effect, with
      retention of embryos in the oviduct. In contrast to estradiol-17beta, MXC at the
      dose used in this study did not alter tubal transport of embryos. Also in
      contrast to estradiol-17beta, MXC increased the percentage of nuclear
      fragmentation and micronuclei. In preimplantation embryos, MXC and estradiol
      17beta both suppressed embryo development. MXC effects were, however, different
      from those of estradiol-17beta, indicating a difference in mechanism of action,
      possibly due to cytotoxicity and induction of apoptosis.

PMID- 12507663
TI  - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on chorionic gonadotropin
      secretion by human trophoblasts.
AB  - This study tests the idea that the environmental toxicant, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), affects human trophoblast differentiation and
      alters the secretion of chorionic gonadotropin (CG). Primary cultures of
      cytotrophoblast cells were incubated under differentiation-inducing and
      nondifferentiation-inducing conditions in the presence or absence of different
      concentrations of TCDD. Levels of immunoreactive CG as well as bioactive CG were
      measured in culture supernatants. TCDD caused a significant increase in the
      secretion of immunoreactive CG from differentiated trophoblast cultures but had
      no effect on the secretion of bioactive hormone. The net effect was a TCDD
      dependent reduction in the CG bioactive/immunoreactive (B/I) ratio for
      differentiated trophoblast cultures. TCDD had no effect on immunoreactive or
      bioactive CG secretion by undifferentiated trophoblasts. Immunocytochemical
      studies showed that TCDD had no effect on the morphologic differentiation of
      trophoblast cells as determined by staining nuclei and desmosomal proteins. On
      the other hand, immunocytochemical staining for CG was increased in cells exposed
      to TCDD compared to control cells. These in vitro results support earlier in vivo
      studies in macaques suggesting that trophoblast is a target for TCCD and that
      TCDD-induced early pregnancy loss is accompanied by a decrease in the CG B/I
      ratio.

PMID- 12507664
TI  - Reproductive toxicology profile of emtricitabine in mice and rabbits.
AB  - Reproductive and developmental toxicology studies were conducted with
      emtricitabine, a nucleoside analog in development for treatment of human
      immunodeficiency virus (HIV) (Phase III) and hepatitis B (HBV) (Phase III)
      infections. Oral doses up to 1000 mg/kg/day provided daily area under the curve
      (AUC(0-->24)) exposure to pregnant animals approximately 60- (mice) to 120-fold
      (rabbits) higher than that in humans at the recommended dose of 200 mg given once
      per day. In a mouse fertility study, emtricitabine had no effect on fertility,
      sperm count, or early embryonic development. There was no increased incidence of
      malformations in mouse and rabbit embryofetal toxicology studies. The average
      ratio for concentration of emtricitabine in fetal plasma divided by concentration
      in maternal plasma was approximately 0.40 in mice and 0.50 in rabbits, a finding
      that indicates significant exposure of the fetuses to emtricitabine. The
      development and fertility of F(1) progeny were unaffected by emtricitabine in a
      mouse pre- and post-natal study. These data demonstrate a favorable pre-clinical
      reproductive safety profile for emtricitabine.

PMID- 12507665
TI  - Safety and pharmacokinetics of oral lansoprazole in preadolescent rats exposed
      from weaning through sexual maturity.
AB  - Proton pump inhibitors, the reference standard in adults with acid-related
      disorders, are increasingly being used in children despite limited pediatric
      safety and pharmacokinetic data. This study evaluated these parameters in rats
      aged 21-60 days, which approximately correlates with children aged 2-11 years.
      Lansoprazole at doses of 0, 5, 15, 50, or 150 mg/kg per day was administered to
      Sprague-Dawley rats from weaning through sexual maturity. Safety assessments
      included clinical, neurobehavioral, ophthalmologic, and gender-specific
      developmental milestones, clinical pathology including urinalysis, organ weight
      (at necropsy), and histopathologic evaluation. Blood samples for pharmacokinetics
      were collected on the first and last days of treatment. After the end of dosing,
      decreases in body weight gain, serum total protein and albumin (males), and
      microcytic hypochromic anemia were observed at doses of > or =50mg/kg per day,
      and hypoglycaemia (females) at 150 mg/kg per day. Selected groups exhibited
      increases in absolute and relative duodenal and stomach weights (> or =15 mg/kg
      per day), decreases in absolute and relative thymus weights (> or =50 mg/kg per
      day), increased relative liver weights (> or =50 mg/kg per day), and chronic
      adhesions to the spleen (> or =15 mg/kg per day). No other changes were observed.
      The area under the curve values in 60-day-old rats was less than those observed
      in 21-day-old rats. Areas under the curve values for lansoprazole were higher in
      female than male 60-day-old rats. No unexpected signs of toxicity were observed
      in the current preadolescent rats relative to those observed in adult rats in
      previous studies. The NOEL in preadolescent rats was similar to adults and gives
      a safety margin of one- to five-fold relative to the pediatric dose (0.87 mg/kg
      in 2-11-year-olds). These results provide comparative evidence for the value of
      studies in rats to support safety in a pediatric population.

PMID- 12507667
TI  - A hypothesis out-of-date. the diet-heart idea.
AB  - An almost endless number of observations and experiments have effectively
      falsified the hypothesis that dietary cholesterol and fats, and a high
      cholesterol level play a role in the causation of atherosclerosis and
      cardiovascular disease. The hypothesis is maintained because allegedly
      supportive, but insignificant findings, are inflated, and because most
      contradictory results are misinterpreted, misquoted or ignored.

PMID- 12507668
TI  - Is atherosclerotic vascular disease related to a high-fat diet?

PMID- 12507670
TI  - Sun exposure and number of nevi in 5- to 6-year-old European children.
AB  - The occurrence and number of melanocytic nevi are among the most important known
      risk factors for the development of malignant melanoma. Studying the causes of
      nevi should lead to successful strategies in the prevention of melanoma. Among
      11,478 white German children of preschool age the association between benign
      melanocytic nevi and a number of risk factors for skin cancer was examined. We
      found that subjects with a reported history of increased sun exposure, for
      example, painful sunburns, and an increased number of holidays in foreign
      countries with a sunny climate had significantly higher nevus counts than
      individuals without these characteristics. Our results provide further evidence
      that nevus counts may not only be part of a genetic predisposition but also a
      result of increased exposure to ultraviolet radiation. Together with the fact
      that a high nevus count is the most relevant risk factor for malignant melanoma,
      the results strongly indicate a connection between UV-radiation and the
      development of melanocytic skin cancer. In conclusion, strategies to reduce the
      incidence of melanoma should begin with young children.

PMID- 12507671
TI  - Diabetes mellitus as a contributor to the risk of acute myocardial infarction.
AB  - The risk of nonfatal acute myocardial infarction (AMI) has been studied in
      relation to diabetes and other risk factors, combining data from three Italian
      case-control studies including 1,737 cases with nonfatal AMI and 2,317 controls
      in hospital for acute diseases unrelated to AMI risk factors. The multivariate
      odds ratio (OR) of AMI for diabetes was 2.3 (95% confidence interval, 1.8-2.9);
      the association with AMI risk was apparently stronger in patients diagnosed with
      diabetes when aged <40 years (OR 2.9), and in women (OR 4.4). When the combined
      effect of diabetes and other known risk factors on the risk of AMI was
      considered, compared to nondiabetic subjects with each factor at the lowest risk
      level, the OR for diabetic subjects was 4.7 in smokers, 2.8 in heavy coffee
      drinkers, 2.7 in those with higher body mass index, 3.4 in patients with high
      cholesterol levels, 3.3, 4.3, and 2.7 for diabetic subjects with history of
      hyperlipidemia, hypertension, and obesity, respectively, and 4.3 for those with a
      family history of AMI in first degree relatives. The association of each risk
      factor was much stronger in diabetic women. Preventive measures to reduce the
      prevalence of each additional risk factors in diabetic subjects could led to a
      substantial reduction of risk of AMI.

PMID- 12507672
TI  - A risk model for the prediction of recurrent falls in community-dwelling elderly:
      a prospective cohort study.
AB  - The object of this article was to determine the predictive value of risk factors
      for recurrent falls and the construction of a fall risk model as a contribution
      to a mobility assessment for the identification of community-dwelling elderly at
      risk for recurrent falling in general practice. The design was a prospective
      cohort study (n = 311). There were four primary health care centers. A sample
      stratified on previous falls, age, and gender of community-dwelling elderly
      persons aged 70 years or over (n = 311) was taken from the respondents to a mail
      questionnaire (n = 1660). They were visited at home to assess physical and mental
      health, balance and gait, mobility and strength. A 36-week follow-up with
      telephone calls every 6 weeks was conducted. Falls and fall injuries were
      measured. During follow-up 197 falls were reported by 33% of the participants:
      one fall by 17% and two or more falls by 16%. Injury due to a fall was reported
      by 45% of the fallers: 2% hip fractures, 4% other fractures, and 39% minor
      injuries. A fall risk model for the prediction of recurrent falls with an area
      under the curve (AUC) of 0.79, based on logistic regression analysis, showed that
      the main determinants for recurrent falls were: an abnormal postural sway (OR
      3.9; 95% Cl 1.3-12.1), two or more falls in the previous year (OR 3.1; 95% Cl 1.5
      6.7), low scores for hand grip strength (OR 3.1; 95% Cl 1.5-6.6), and a
      depressive state of mind (OR 2.2; 95% CI 1.1-4.5). To facilitate the use of the
      model for clinical practice, the model was converted to a "desk model" with three
      risk categories: low risk (0-1 predictor), moderate risk (two predictors), and
      high risk (> or =3 predictors). A fall risk model converted to a "desk model,"
      consisting of the predictors postural sway, fall history, hand dynamometry, and
      depression, provides added value in the identification of community-dwelling
      elderly at risk for recurrent falling and facilitates the prediction of recurrent
      falls.

PMID- 12507673
TI  - Prognosis of small hepatocellular carcinoma treated by percutaneous ethanol
      injection and transcatheter arterial chemoembolization.
AB  - This study was conducted to assess the progression and prognosis of a total of
      108 patients with hepatocellular carcinoma (HCCs) smaller than 5 cm in diameter
      treated by percutaneous ethanol injection (PEI) with or without transcatheter
      arterial chemoembolization. All patients were classified as Child-Pugh A (n = 84)
      or B (n = 24). Logarithm of hazard rate (per month) with time since therapy was
      assessed. The Weibull model was used to elucidate the effect of pretreatment
      clinico-pathologic variables on prognosis. The rate of death increased by 4.7%
      (95% CI: 3.7-5.7%) per month since treatment. Child-Pugh B status was associated
      with a 2.8-fold risk (95% CI: 1.52-5.16) of death. Those with a high level of AST
      or alcoholic cirrhotics had a two-fold risk (95% CI:1.14-3.42) for death from
      HCC. Our results suggest the optimal frequency of clinical surveillance of small
      HCC cases after treatment should take account of increased hazard rate with time
      and the roles of pretreatment clinico-pathologic variables.

PMID- 12507674
TI  - Gender-specific changes in quality of life following cardiovascular disease: a
      prospective study.
AB  - Gender-specific changes in Quality of Life (QoL) following cardiovascular disease
      (CVD) were studied in 208 patients to determine whether gender-related
      differences in postmorbid QoL result from differences in disease severity,
      premorbid QoL, or different CVD-related recovery. Premorbid data were available
      from a community-based survey. Follow-ups were done at 6 weeks, 6 months, and 12
      months after diagnosis. Results showed that females had worse QoL at all three
      postmorbid assessments compared to males. However, multivariate analyses
      adjusting for premorbid gender differences and disease severity showed no
      significant gender-related differences for physical and psychologic functioning.
      Therefore, gender differences in QoL following CVD mainly result from premorbid
      differences in QoL, age, comorbidity, and disease severity at the time of
      diagnosis, and do not appear to be the consequence of gender-specific recovery.
      However, in clinical practice it is important to acknowledge the poorer QoL of
      females following CVD.

PMID- 12507675
TI  - Deterministic models for breast cancer progression: application to the
      association between mammographic parenchymal pattern and histologic grade of
      breast cancers.
AB  - Dense mammographic patterns are a risk factor for breast cancer. In a recent case
      control study, dense patterns were observed to be associated with a higher
      relative risk estimate for the more aggressive grade 3 tumors than for grade 1 or
      2 tumors. The present study was designed to ascertain, by reference to odds ratio
      estimates of relative risk by tumor size and histologic grade, whether this was
      more likely to be due to increased innate predisposition of dense parenchymal
      patterns to grade 3 tumors, or to dedifferentiation of cases missed at screening
      due to dense patterns. If the observation were due entirely to dedifferentiation,
      then for a given size the relative risk of grade 3 tumors would be the same as
      for grades 1-2. Size-specific relative risks of grade 3 tumors were higher than
      those of grade 1-2 tumors. It is concluded that the majority of the enhanced risk
      of grade 3 tumors is due to enhanced innate predisposition to grade 3 tumors in
      dense breasts.

PMID- 12507676
TI  - A high response is not essential to prevent selection bias: results from the
      Leiden 85-plus study.
AB  - We tested the hypothesis that an additional effort to increase the response rate
      would diminish selection bias in a community-based cohort study. In the Leiden 85
      plus Study, all subjects of the town of Leiden who had reached their 85th
      birthday were informed of the study by mail and then asked to participate by
      telephone. In an additional recruitment stage, those subjects who did not
      participate directly were visited and personally asked to participate. When these
      subjects refused, some nonresponse questions were asked. In this way we collected
      data on the whole source population. Of 691 eligible elderly subjects, 511
      subjects (74%) participated directly. Of those who did not participate directly,
      88 subjects participated after the additional effort. The response rate increased
      from 74% to 87%. Compared to the 511 subjects who directly participated, the 88
      subjects who entered the study after the additional effort had poorer health and
      lower survival. The subjects who refused were more healthy and had poorer mood.
      The direct sample did not differ from the source population with respect to socio
      demographics, health, and mortality. In conclusion, we showed that given a
      moderately high direct response the additional effort was effective in increasing
      the response rate, but was also selective and was not necessary to prevent
      selection bias.

PMID- 12507677
TI  - Effect of applying different "levels of evidence" criteria on conclusions of
      Cochrane reviews of interventions for low back pain.
AB  - The objective of this study was to examine the consistency of conclusions of
      Cochrane systematic reviews when different criteria are used to determine levels
      of evidence. We reanalyzed the data in six Cochrane reviews of conservative
      treatment of low back pain by applying three additional sets of "levels of
      evidence" criteria. Overall agreement between the conclusions attained with the
      different levels of evidence criteria was only "fair" (multirater kappa
      coefficient 0.33; 95% CI 0.28 to 0.38). For example, the four sets of levels of
      evidence criteria produced four conclusions on the efficacy of back school:
      "strong evidence that back schools are effective," "weak evidence," "limited
      evidence," and "no evidence." Pairwise agreement between the four pooling systems
      ranged from slight to substantial (kappas ranging from 0.10 to 0.80). Different
      rules for determining levels of evidence in systematic reviews produce markedly
      different conclusions on treatment efficacy. Crown

PMID- 12507678
TI  - The role of health care providers and significant others in evaluating the
      quality of life of patients with chronic disease.
AB  - Health-related quality of life (HRQL) studies sometimes rely, in part, on proxy
      information obtained from patients' significant others (spouse or close
      companion) or health care providers. This review: (1) provides a quantitative
      analysis of the results that have been reported in recent studies assessing the
      level of agreement between patient and proxy HRQL ratings, and (2) addresses a
      number of key methodological issues surrounding the use of proxy raters in HRQL
      research. This review concentrates on 23 studies, published between 1991-2000,
      that describe patient-proxy agreement for a number of well-known multidimensional
      HRQL instruments. In general, moderate to high levels of patient-proxy agreement
      were reported. Lower levels of agreement were found predominantly in studies
      employing a small sample size (approximately 50 patient-proxy pairs or less). In
      larger studies comparing patients and their significant others, median
      correlations were between 0.60-0.70 for physical HRQL domains and about 0.50 for
      psychosocial domains. Mixed results were reported in studies comparing patients
      and their health care providers, but most of these studies employed a relatively
      small sample size. Proxy raters tended to report more HRQL problems than patients
      themselves, but the magnitude of observed differences was modest (median
      standardized differences of about 0.20). Based on the current evidence, we
      conclude that judgements made by significant others and health care providers
      about several aspects of patients' HRQL are reasonably accurate. Substantial
      discrepancies between patient and proxy ratings occur in a minority of cases. We
      recommend that future studies focus on: (a) the reliability and validity of proxy
      ratings according to common psychometric methods, and (b) the balance between
      information bias due to proxy ratings and potential selection bias due to
      exclusion of important patient subgroups from HRQL studies.

PMID- 12507679
TI  - Evaluation of Charlson's comorbidity index in elderly living in nursing homes.
AB  - The object of this article was to validate the predictive value of Charlson's
      comorbidity index for the prediction of short-term mortality or morbidity in
      elderly people. The design was a cohort study comparing survival and
      hospitalization in institutionalized elderly people with different levels of
      comorbidity at baseline. The setting was 16 Flemish nursing homes for the
      elderly. The subjects were 2,727 inhabitants of which full data were available
      for 2,624. The outcome measures were hazard ratios resulting from Cox regression
      analysis, comparing 6 months survival in patients with moderate and a high level
      to low level of comorbidity. Odds ratios resulting from multiple logistic
      regression analysis comparing the occurrence of at least one hospitalization
      during the follow-up period in surviving patients of the same groups. Mortality
      adjusted for age group was significantly increased in patients with a moderate
      (HR = 2.00) and even more in those with a high level (HR = 3.62) of comorbidity.
      Hospitalization was more frequent in both groups (OR = 1.54 and 2.19,
      respectively), with statistical significance only being reached for the highest
      group. Adjustment for age, gender, mobility status, and disorientation did not
      change the general picture. Charlson's comorbidity index is a predictor of short
      term mortality in institutionalized elderly patients and, to a lesser extend,
      also of hospitalization. These results support its use as a measure for
      introducing comorbidity as a covariable in longitudinal studies with a geriatric
      population.

PMID- 12507680
TI  - Improving private pharmacy practice: a multi-intervention experiment in Hanoi,
      Vietnam.
AB  - The objective of this study was to assess the effects of a multicomponent
      intervention on private pharmacy practice. From 641 private pharmacies in Hanoi,
      68 pharmacies were randomly selected and matched into 34 pairs. Each pair
      consisted of a control and an intervention pharmacy. Three interventions were
      applied sequentially: Regulatory enforcement, Education, and Peer influence. Four
      tracer conditions were selected: uncomplicated acute respiratory infection (ARI),
      sexually transmitted disease (STD), requesting the prescription-only drugs
      prednisolone, and a short course of cefalexin. Practice was assessed through the
      Simulated Client Method (SCM). The intervention pharmacies improved significantly
      compared to the control pharmacies (P <.05) in all tracer conditions. For ARI,
      antibiotic dispensing decreased (P <.02) and questions regarding breathing
      increased (P <.01). For STD, advice to go to the doctor and dispensing the
      correct syndromic treatment increased (P <.01). Dispensing of prednisolone and
      cefalexin decreased (P <.01) and prescription requests increased (P <.01). Our
      conclusion is that it is possible to improve private pharmacy practice with a
      multicomponent intervention.

PMID- 12507681
TI  - A taxonomy for responsiveness?

PMID- 12507682
TI  - Prognostic index for stroke mortality.

PMID- 12507683
TI  - Future directions in research with presymptomatic individuals carrying the gene
      for Huntington's disease.
AB  - Presymptomatic individuals carrying the gene for Huntington's disease (HD)
      provide researchers with a unique opportunity of learning more about the
      neuropathophysiology, symptom onset, behavioural functioning, and mediating
      factors of this fatal disease. In this review, we attempt to demonstrate that
      research over the last 8 years, since the isolation of the gene, has remained at
      large controversial. Although we are aware of some of the factors that can
      influence age at onset and disease progression, we are still unable to determine
      exactly when an individual will develop HD symptoms, and how fast these symptoms
      will progress. In an era rapidly advancing with respect to therapeutic
      intervention that could forestall the onset and progression of HD, systematic
      research with improved inclusion criteria is paramount. A greater understanding
      of the time course of the disease would be beneficial not only in monitoring the
      effectiveness of future treatments, but also in determining the most appropriate
      time to administer them. Finally, we present various ethical considerations, as
      well as put forward various recommendations that could assist in better
      diagnosing preclinical deficits in presymptomatic individuals.

PMID- 12507684
TI  - Signal transduction and neurosurvival in experimental models of brain injury.
AB  - Brain injury and neurodegenerative disease are linked by their primary
      pathological consequence-death of neurons. Current approaches for the treatment
      of neurodegeneration are limited. In this review, we discuss animal models of
      human brain injury and molecular biological data that have been obtained from
      their analysis. In particular, signal transduction pathways that are associated
      with neurosurvival following injury to the brain are presented and discussed.

PMID- 12507685
TI  - "Binge" cocaine differentially alters preproenkephalin mRNA levels in guinea pig
      brain.
AB  - Male Hartley guinea pigs were administered i.p. injections of cocaine or saline
      for 2 or 7 days in a "binge" paradigm. RNA was isolated from dissected brain
      regions and levels of preproenkephalin mRNA and total RNA were quantified by
      RNase protection assays. Following 2 days of "binge" cocaine administration, no
      significant alterations in preproenkephalin mRNA levels were detected in six
      brain regions. Following 7 days of cocaine administration, however, lower levels
      of preproenkephalin mRNA were observed in the nucleus accumbens and hypothalamus
      of cocaine-treated animals and higher levels in the frontal cortex and amygdala.
      These findings differed from previous studies in the rat, so an additional
      experiment was performed with animals treated at the 7 day time point. For
      increased statistical power, data from the two experiments were combined and
      examined by two-way ANOVAs; in this combined analysis, increases in
      preproenkephalin mRNA were observed in frontal cortex, amygdala, and hippocampus,
      decreases were found in the nucleus accumbens and hypothalamus, with no change in
      thalamus, caudate putamen, or cerebellum. These observed differences between
      guinea pigs and rats make this species an interesting model for neurobiological
      studies of cocaine-induced alterations in neuropeptide gene expression in the
      mammalian brain.

PMID- 12507686
TI  - Cholinergic mechanism in the lateral septal area is involved in the stress
      induced blood pressure increase in rats.
AB  - Previously, we demonstrated that the rostral part of the ventral zone of the
      lateral septal area (LSV) was involved in the restraint stress-induced pressor
      response. It is suggested that there exist acetylcholine receptors responsible
      for blood pressure increase in the caudal part of the lateral septal area. In
      this study, we examined whether acetylcholine receptors responsible for pressor
      responses also exist in the rostral part of the LSV and whether these
      acetylcholine receptors are involved in the stress-induced pressor response in
      rats. Microinjection of either carbachol (10-100pmol) or physostigmine (0.46 and
      1.5nmol) into the LSV caused a dose-dependent increase in blood pressure. The
      pressor response to carbachol (30pmol) was inhibited by the M1 antagonist
      pirenzepine and the M3 antagonist 4-DAMP mustard but not by the M2 antagonist
      methoctramine injected into the LSV. Bilateral microinjections of the M1/M3
      antagonist 4-DAMP (1nmol) inhibited the restraint stress-induced pressor
      response. These findings suggest that M1/M3 muscarinic receptors responsible for
      blood pressure increase exist in the rostral part of the LSV and they are partly
      involved in the stress-induced pressor response.

PMID- 12507687
TI  - Effects of intracisternal injection of interleukin-6 on nociceptive jaw opening
      reflex and orofacial formalin test in freely moving rats.
AB  - The present study was performed to investigate the effects of central cytokines
      on the modulation of nociception in the orofacial area. To achieve this purpose,
      a nociceptive jaw opening reflex and an orofacial formalin test were monitored
      before and after intracisternal administration of interleukin-6 (IL-6) in freely
      moving rats. In the nociceptive jaw opening reflex, the digastric electromyogram
      (dEMG) was not significantly changed after intracisternal injection of 200 pg and
      2 ng IL-6. However, 20 ng IL-6 suppressed dEMG to 74+/-7% of the control values.
      In the inflammatory orofacial formalin test, intracisternal injection of 200 pg
      and 2 ng IL-6 did not change the number of noxious behavioral responses produced
      by formalin injection. However, 20 ng IL-6 injected intracisternally
      significantly increased the number of noxious behavioral responses produced by
      formalin. The hyperalgesic action of intracisternal IL-6 in the orofacial
      formalin test was blocked by pretreatment with interleukin-1 (IL-1) receptor
      antagonist. These results suggest that IL-6 injected intracisternally modulates
      the transmission of nociceptive information in the orofacial area. However, the
      hypo/hyper-algesic response of central cytokines seems to depend on the orofacial
      pain model. The hyperalgesic response of central IL-6 seems to be mediated by the
      IL-1 receptor.

PMID- 12507688
TI  - Neurotransmitter release and its presynaptic modulation in the rat hippocampus
      after selective damage to cholinergic or/and serotonergic afferents.
AB  - Male Long-Evans rats sustained injections of 5,7-dihydroxytryptamine (5,7-DHT)
      into the fimbria-fornix and the cingular bundle or/and intraseptal injections of
      192 IgG-saporin to induce serotonergic or/and cholinergic hippocampal
      denervations; Sham-operated rats served as controls. Four to ten weeks after
      lesioning, we measured (i). the electrically evoked release of acetylcholine
      ([3H]ACh), noradrenaline ([3H]NA) and serotonin ([3H]5-HT) in hippocampal slices
      in the presence of drugs acting on auto- or heteroreceptors, (ii). the nicotine
      evoked release of NA and (iii). the choline acetyltransferase (ChAT) activity and
      the concentration of monoamines in homogenates. Saporin lesions reduced the
      accumulation of [3H]choline, the release of [3H]ACh and the ChAT activity, but
      increased the concentration of NA and facilitated the release of [3H]NA evoked by
      nicotine. 5,7-DHT lesions reduced the accumulation and the release of [3H]5-HT,
      the concentration of 5-HT, and also facilitated the release of [3H]NA evoked by
      nicotine. Accumulation and electrically evoked release of [3H]NA were not altered
      by either lesion. The combination of both toxins resulted in an addition of their
      particular effects. The 5-HT(1B) receptor agonist, CP 93129, and the muscarinic
      agonist, oxotremorine, reduced the release of [3H]ACh in control and 5,7-DHT
      lesioned rats; in rats injected with saporin, their effects could not be measured
      reliably. CP 93129 and the alpha(2)-adrenoceptor agonist, UK 14304, reduced the
      release of [3H]5-HT in all groups by about 65%. IN CONCLUSION: (i). selective
      neurotoxins can be combined to enable controlled and selective damage of
      hippocampal transmitter systems; (ii). 5-HT exerts an inhibitory influence on the
      nicotine-evoked release of NA, but partial serotonergic lesions do not influence
      the release of ACh at a presynaptic level and (iii). presynaptic modulatory
      mechanisms involving auto- and heteroreceptors may be conserved on fibres spared
      by the lesions.

PMID- 12507689
TI  - Central alpha(2) adrenergic receptors and cholinergic-induced salivation in rats.
AB  - Salivation induced by intraperitoneal (i.p.) injections of pilocarpine
      (cholinergic agonist) is reduced by intracerebroventricular (i.c.v.) injections
      of moxonidine (alpha(2) adrenergic and imidazoline receptor agonist). In the
      present study, we investigated the involvement of central alpha(2) adrenergic
      receptors in the inhibitory effect of i.c.v. moxonidine on i.p. pilocarpine
      induced salivation. Male Holtzman rats with stainless steel cannula implanted
      into the lateral ventricle (LV) were used. Saliva was collected using pre
      weighted small cotton balls inserted into the animal's mouth under ketamine (100
      mg x kg(-1)) anesthesia. Salivation was induced by i.p. injection of pilocarpine
      (4 micromol x kg(-1)). Pilocarpine-induced salivation was reduced by i.c.v.
      injection of moxonidine (10 nmol) and enhanced by i.c.v. injections of either RX
      821002 (160 nmol) or yohimbine (320 nmol). The inhibitory effect of i.c.v.
      moxonidine on pilocarpine-induced salivation was abolished by prior i.c.v.
      injections of the alpha(2) adrenergic receptor antagonists, RX 821002 (160 nmol)
      or yohimbine (160 and 320 nmol). The alpha(1) adrenergic receptor antagonist
      prazosin (320 nmol) injected i.c.v. did not change the effect of moxonidine on
      pilocarpine-induced salivation. The results suggest that moxonidine acts on
      central alpha(2) adrenergic receptors to inhibit pilocarpine-induced salivation,
      and that this salivation is tonically inhibited by central alpha(2) adrenergic
      receptors.

PMID- 12507690
TI  - Brain habituation during repeated exposure to fearful and neutral faces: a
      functional MRI study.
AB  - Central nervous system habituation in humans was studied using functional
      magnetic resonance imaging and repeated presentations of single fearful and
      neutral faces. Habituation of blood-oxygenation-level-dependent (BOLD) signal
      during exposure to face stimuli, collapsed over fearful and neutral expressions,
      was evident in the right amygdala and hippocampus, as well as in the
      medial/inferior temporal cortex bilaterally. In the hippocampus, significantly
      greater habituation was evident on the right as compared to the left side, which
      could reflect the visual nature of the stimuli. There were no time by expression
      interaction effects in these regions, suggesting similar neural attenuation rates
      to fearful and neutral face stimuli. These results indicate that brain regions
      involved in novelty detection and memory processing habituate at similar rates
      regardless of whether the face in focus displays an aversive emotional expression
      or not.

PMID- 12507691
TI  - Melatonin inhibits the substance P-induced secretion of vasopressin and oxytocin
      from the rat hypothalamo-neurohypophysial system: in vitro studies.
AB  - The aim of the present investigations was to study the influence of substance P
      (a member of a family of peptides known as tachykinins) on basal and K(+)-evoked
      vasopressin (AVP) and oxytocin (OT) release from rat hypothalamo-neurohypophysial
      system in vitro as well as to determine whether this effect of substance P is
      sensitive to melatonin. The present results show that substance P stimulates
      basal AVP and OT release from isolated hypothalamo-neurohypophysial system, when
      used at the concentrations of 10(-6) and 10(-7)M/l. At the concentration of 10(
      9)M/l, however, substance P was found to stimulate the in vitro secretion of AVP,
      but not that of OT. Melatonin diminished basal release of AVP; it also
      significantly inhibited the substance P-stimulated secretion of AVP and OT. K(+)
      evoked release of the neurohypophysial hormones was not further modified by
      either substance P or melatonin. The present results show that the stimulatory
      effect of substance P on basal release of AVP and OT from rat hypothalamo
      neurohypophysial system in vitro is sensitive to inhibitory influence of
      melatonin.

PMID- 12507692
TI  - Differential expression of vasopressin V1a and V1b receptors mRNA in the brain of
      renin transgenic TGR(mRen2)27 and Sprague-Dawley rats.
AB  - Recent evidence indicates that renin transgenic rats TGR(mRen2)27 (TGR) manifest
      increased activity of the central vasopressinergic system. Because one of the
      reasons for this finding could be an increased synthesis of vasopressin
      receptors, we determined in the present study expression of V1a and V1b
      vasopressin receptors (R) mRNA in the brain of TGR rats and of their parent
      Sprague-Dawley (SD) strain. Competitive PCR method was applied for quantitative
      analysis of V1a and V1b receptors mRNA in the preoptic, diencephalic,
      mesencephalopontine and medullary regions. V1aR mRNA expression was similar in SD
      and TGR rats in the preoptic, diencephalic and mesencephalopontine regions. In
      the medullary region expression of V1aR mRNA was significantly lower in TGR than
      in SD rats. V1bR mRNA did not differ in TGR and SD rats in the preoptic,
      diencephalic and medullary region whereas it was significantly elevated in the
      mesencephalopontine region. The results provide evidence for differential
      regulation of V1a and V1b receptors genes in the brain stem of TGR rats that is
      manifested by downregulation of V1aR mRNA in the medulla and upregulation of V1bR
      mRNA in the mesencephalopontine region.

PMID- 12507693
TI  - Distributed neural systems for temporal production: a functional MRI study.
AB  - Using functional magnetic resonance imaging (fMRI), we investigated the neural
      substrates for computing time intervals. Five right-handed males were asked to
      judge if a digit probe belonged to a string of digits presented immediately
      before but to provide their response only after 1.5s had elapsed. This time
      estimation condition, compared with control working memory and motor tasks, was
      associated with increased activity in the middle occipital gyri, in the right
      inferior parietal lobe, and bilaterally in the prefrontal cortex. We argue that
      activity elicited in the occipital lobe provides duration information about
      visual stimuli that can be quantified at the level of the inferior parietal lobe.
      Comparison with time reference information depends on the bilateral prefrontal
      cortex.

PMID- 12507695
TI  - Vagus nerve stimulation in awake rats reduces formalin-induced nociceptive
      behaviour and fos-immunoreactivity in trigeminal nucleus caudalis.
AB  - Besides its well-established efficacy in epilepsy, vagus nerve stimulation (VNS)
      may be of potential interest in pain treatment. It has, however, not yet been
      assessed in animal pain models with the devices and stimulation protocols used in
      humans. We have therefore studied in awake rats the effects of left cervical VNS
      on trigeminal nociception using an implantable electrode and stimulator (NCP
      Cyberonics). VNS was applied for 24h at 2 mA intensity, 20 Hz frequency, 0.5 ms
      pulse width and a duty cycle of 20s ON/18s OFF. As a nociceptive stimulus, we
      injected formalin into the left mystacial vibrissae, assessed behaviour for 45
      min and sacrificed the animals 45 min later. Fos-immunoreactive (Fos-Ir) neurons
      were counted in laminae I-II of trigeminal nucleus caudalis (TNC) on both sides.
      We used three groups of control animals: VNS without formalin, formalin without
      VNS and sham VNS (implanted without stimulation or formalin). Whereas sham VNS
      had no significant effect, VNS alone increased Fos expression in ipsilateral TNC
      in addition to the expected increase in nucleus tractus solitarius. It also
      significantly attenuated the increase of Fos-Ir neurons observed in ipsilateral
      TNC laminae I-II after formalin injection. If the proper VNS effect on Fos
      expression was subtracted, the reduction of formalin-induced nociceptor
      activation was 55%. VNS also reduced nociceptive behaviour on average by 96.1%
      during the early phase (0-6 min) and by 60.7% during the late phase (6-45 min)
      after the formalin injection. These results suggest that VNS applied with a
      device used in human therapy may have in awake rats a significant antinociceptive
      effect in a model of trigeminal pain.

PMID- 12507696
TI  - Modulation of inhibitory synaptic activity by a non-alpha4beta2, non-alpha7
      subtype of nicotinic receptors in the substantia gelatinosa of adult rat spinal
      cord.
AB  - The GABA/glycine-mediated inhibitory activity in the substantia gelatinosa (SG)
      of the spinal cord is critical in the control of nociceptive transmission. We
      examined whether and how SG inhibitory activity might be regulated by neuronal
      nicotinic receptors (nAChRs). Patch-clamp recordings were performed in SG neurons
      of spinal slice preparations from adult rats. We provided electrophysiological
      evidence that inhibitory presynaptic terminals in the SG expressed nAChRs and
      their activation resulted in large increases in the frequency of spontaneous and
      miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in over 90% SG
      neurons tested. The enhancement of inhibitory activity was mediated by increases
      in the release of GABA/glycine, and direct Ca(2+) entry through SG presynaptic
      nAChRs appeared to be involved. Miniature IPSC frequency could be enhanced by the
      nAChR agonists nicotine or cytisine. Nicotine could still elicit large increases
      in mIPSC frequency in the presence of the alpha4beta2 nAChR antagonist dihydro
      beta-erythroidine (5 microM) and the alpha7 nAChR-selective antagonist
      methyllycaconitine (40 nM). However, nicotine did not produce a significant
      enhancement of mIPSC frequency in the presence of the broad spectrum nAChR
      antagonist mecamylamine (5 microM). Nicotinic agonist-evoked whole-cell currents
      from SG neurons and the antagonist profiles also indicated the presence of a
      subtype of nAChRs, which were different from the major central nervous system
      nAChR subtypes, i.e. alpha4beta2* or alpha7 nAChRs. Together, our results suggest
      that a subtype of nAChR, possibly alpha3beta4* nAChR or a new nAChR type, is
      highly expressed at the inhibitory presynaptic terminals in SG of adult rats and
      play a role in the control of inhibitory activity in SG.

PMID- 12507697
TI  - Abnormal brain processing of cutaneous pain in patients with chronic migraine.
AB  - Syndromes with chronic daily headache include chronic migraine (CM). The reason
      for the transformation of migraine into chronic daily headache is still unknown.
      In this study, we aimed to evaluate heat pain thresholds and event-related
      potentials following CO(2)-laser thermal stimulation (LEPS) in hand and facial
      regions in patients with CM, to show changes in nociceptive brain responses
      related to dysfunction of pain elaboration at the cortical level. The results
      were compared with findings from normal control subjects and from subjects who
      suffer from migraine without aura. The effects of stimulus intensity, subjective
      pain perception and attention were monitored and compared with features of the
      LEPS. Twenty-five CM patients, 15 subjects suffering from migraine without aura
      and 15 normal control subjects were enrolled in the study. LEPS amplitude
      variation was reduced in CM patients with respect to the perceived stimulus
      intensity, in comparison with migraine without aura patients and control
      subjects. In both headache groups, the distraction from the painful laser
      stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in
      comparison with control subjects. These results suggest an abnormal cortical
      processing of nociceptive input in CM patients, which could lead to the chronic
      state of pain. In both headache groups, an inability to reduce pain elaboration
      during an alternative cognitive task emerged as an abnormal behaviour probably
      predisposing to migraine.

PMID- 12507698
TI  - Psychosocial factors associated with chronic pain in adolescents.
AB  - A number of psychosocial factors have been associated with the onset,
      exacerbation and/or maintenance of chronic pain in adolescents. The present study
      was conducted to evaluate the relative importance of vulnerability,
      reinforcement, and modeling. We compared 222 adolescents with chronic pain and no
      documented physiological etiology (headache, back, limb and abdominal pain) with
      148 controls and their (respectively 183 vs. 127) parents. Analyses showed that
      adolescents with chronic pain are more vulnerable in terms of neuroticism,
      negative fear of failure, and (less) experienced social acceptance. Contrary to
      our expectations, the chronic pain group experienced less reinforcement for their
      pain behavior by both parents and peers than the control group. While the number
      of pain models was higher in the chronic pain group, no differences were found
      between their parents and those of the adolescents without chronic pain in pain
      experience, pain parameters, and pain coping. Regression analyses on the
      contribution of psychosocial factors to chronic pain and its parameters sustained
      the positive relation between vulnerability, (less) pain reinforcement, pain
      models and coping with pain. Furthermore, we also found evidence that gender
      differences have to be taken into account.

PMID- 12507699
TI  - Gender differences in pain characteristics of chronic stable angina and perceived
      physical limitation in patients with coronary artery disease.
AB  - Chronic stable angina pectoris, the chest pain associated with reversible
      myocardial ischemia has detrimental effects on health-related quality of life,
      particularly in women. The limited research on gender differences in chronic
      stable angina suggests that angina may be experienced differently in women and
      that women report greater functional disability related to angina symptoms. No
      studies have examined gender differences in chronic stable angina from a
      multidimensional pain perspective or have included reliable and valid measures of
      pain that would facilitate comparing chronic angina patients with other chronic
      pain populations. The purpose of this descriptive study was to examine gender
      differences in characteristics of chronic stable angina using the short-form
      McGill pain questionnaire (SF-MPQ) and to explore relationships among these pain
      characteristics and perceived limitation in performing physical activities in
      patients with coronary artery disease (CAD) (physical limitation subscale of the
      Seattle angina questionnaire). One hundred and twenty-eight subjects (30.5%
      women) with stable CAD and angina pectoris documented by a cardiologist completed
      study questionnaires in an outpatient cardiology clinic. Results of the study
      suggest that men and women with chronic stable angina had more similarities than
      differences in chest pain characteristics. No significant gender differences were
      demonstrated in total sensory or affective intensity scores, the present pain
      intensity index, or the number of pain words chosen. However, women did report
      significantly greater pain intensity on the SF-MPQ visual analogue scale. Women
      were also significantly more likely to describe their chronic angina as 'hot
      burning' and 'tender' and to have greater intensity of pain for these two
      descriptors. Despite the similarities in pain characteristics, women reported
      greater physical limitation related to anginal pain. The variables of social
      status and years diagnosed with CAD significantly interacted with gender in
      predicting physical limitation suggesting that gender-specific models of physical
      limitation in angina patients need to be explored. To our knowledge, this is one
      of the first studies that has assessed chronic anginal pain using a reliable and
      valid generic pain instrument. More research is needed to better understand the
      nature of gender differences in functional limitation secondary to anginal pain
      and the physiologic, cognitive-perceptual and psychosocial mechanisms that lead
      to angina-related functional disability.

PMID- 12507700
TI  - Cancer breakthrough pain characteristics and responses to treatment at a VA
      medical center.
AB  - The purpose of this study is to analyze cancer breakthrough pain (BP)
      characteristics and how BP responds to conventional cancer pain management.
      Seventy-four cancer pain patients with worst pain severity >or=4 out of 10
      completed the Brief Pain Inventory (BPI), Memorial Symptom Assessment Scale-Short
      Form, Functional Assessment Cancer Therapy and Breakthrough Pain Questionnaires
      (BPQ) at an initial interview. Agency for Health Care Policy and Research (AHCPR)
      cancer pain management guidelines were followed. Pain syndromes and morphine
      equivalent daily dose (MEDD) orally were determined. One-week follow-up
      assessments were obtained in 66 patients with BPI and BPQ. The BP characteristics
      were similar at both time points. On day 1, 52 patients (70%) had BP, and the BP
      was unpredictable in 30 patients (58%). The median time to worst BP severity was
      3 min. Patients with BP had significantly higher worst pain (P<0.001). At week 1,
      the median MEDD doubled from 60 to 120 mg orally, and the number of patients who
      received adjuvant analgesics doubled from 31.1% (23 patients) on day 1 to 62.2%
      (41 patients). At week 1, 21 patients (32%) remained without BP, 21 patients
      (32%) were classified as BP responders and 24 patients (36%) were BP non
      responders. The mean pain relief was similar for all three subgroups, i.e. around
      80%. Compared to BP responders, BP non-responders had significantly higher worst
      pain (P<0.0001), average pain (P<0.004), and higher BPI interference parameters
      and shorter time to worst pain severity. The study confirmed the applicability of
      the BPQ to an US veteran population, and that pain management following the AHCPR
      guidelines is effective for a group of patients with cancer related BP.
      Underlying pain syndromes and the BP location may influence the response of BP to
      treatment. Patients with bone pain located in the spine, back, and pelvis may be
      at risk for resistant BP.

PMID- 12507701
TI  - Contribution of injured and uninjured dorsal root ganglion neurons to pain
      behavior and the changes in gene expression following chronic constriction injury
      of the sciatic nerve in rats.
AB  - Neuropathic pain models, such as the chronic constriction injury (CCI) model, are
      partial nerve injury models where there exist both intact and injured peripheral
      axons. Recent studies suggested that dorsal root ganglion (DRG) neurons with
      intact axons also show the alteration of excitability and gene expression and
      might have some role in the pathophysiological mechanisms of neuropathic pain.
      The incidence of pain-related behavior after the CCI is unstable and variable. In
      the present study, we used activating transcription factor 3 (ATF3) expression as
      a neuronal injury marker, and analyzed a relationship between the number of
      axotomized neurons and the incidence of pain-related behavior. We divided all
      rats into three groups according to the percentage of ATF3-immunoreactive (IR)
      neurons, group 1 (<12.5%), group 2 (12.5-25%), and group 3 (>25%). We found that
      rats in groups 2 and 3 showed thermal hyperalgesia, whereas only the rats in
      group 2 developed tactile allodynia from the third day to the fourteenth day
      after surgery. Rats in group 1 did not show thermal hyperalgesia or tactile
      allodynia. The DRG neurons in group 2 contained ATF3-IR neurons mainly in medium-
      and large-sized neurons. In order to investigate brain-derived neurotrophic
      factor (BDNF) and gamma-aminobutyric acid(A)-receptor (GABA(A)-R) regulation in
      both intact and injured primary afferent neurons after the CCI, we used a double
      labeling method with immunohistochemistry and in situ hybridization, as well as
      double immunofluorescent staining. The CCI induced an increased number of BDNF
      labeled neurons in the ipsilateral DRG and the increase in BDNF expression was
      observed mainly in small- and medium-sized neurons that were mainly ATF3
      negative. On the other hand, the number of GABA(A)-Rgamma2 subunit mRNA-positive
      neurons decreased in the ipsilateral DRG and GABA(A)-R- and ATF3-labeled neurons
      rarely overlapped. These changes in molecular phenotype in intact and injured
      primary afferents may be involved in the pathophysiological mechanisms of
      neuropathic pain produced by partial nerve injury.

PMID- 12507702
TI  - Impact of upper limb complex regional pain syndrome type 1 on everyday life
      measured with a novel upper limb-activity monitor.
AB  - Complex regional pain syndrome type 1 (CRPS1) often leads to serious activity
      limitations in everyday life. To date, however, limitations in patients with
      CRPS1 of an upper limb have not been objectively measured.Therefore, the aim of
      this study was to determine the long-term impact of upper limb CRPS1 on general
      mobility and upper limb usage during everyday life, as measured with a novel
      upper limb-activity monitor (ULAM). In ten female chronic CRPS1 patients and ten
      healthy control subjects, 24-h activity patterns were measured with the ULAM.
      This ULAM consists of body-fixed acceleration sensors, connected to a recorder
      worn around the waist. The ULAM automatically detects upper limb activity during
      mobility-related activities. Several outcome measures related to general mobility
      and upper limb usage were compared between patients and controls. The results
      showed that CRPSI in the dominant upper limb had modest impact on general
      mobility; i.e. on the percentages spent in body positions and body motions and on
      mean intensity of body activity. For upper limb usage outcome measures during
      sitting, there was a marked difference between CRPS1 patients and controls.
      Especially patients with dominant side involvement clearly showed less activity
      of their involved limb during sitting, indicated by significant differences for
      the mean intensity (P=0.014), percentage (P=0.004), and proportion (P=0.032) of
      upper limb activity. It is concluded that these ten chronic CRPS1 patients still
      had limitations in upper limb usage during everyday life, 3.7 years (average)
      after the causative event.

PMID- 12507703
TI  - Analgesia from a peripherally active kappa-opioid receptor agonist in patients
      with chronic pancreatitis.
AB  - Preclinical studies suggest that visceral afferents constitutively express kappa
      opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a
      peripheral site by KOR activation. To test the relevance of these observations to
      humans, we infused, in a randomized, double blind manner, a peripherally
      selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic
      pancreatitis and ongoing abdominal pain despite mu-opioid agonist therapy. Pain
      was assessed using a pain magnitude estimate, an open ended scale of each
      patient's choosing and compared to their rating of pain from a 1.6 cm(2) thermode
      applied to the skin and heated to 49 degrees C for 5s. Normalizing pain scores to
      this rating as 100, pain prior to study drug treatment was 4070, and was
      unaffected by placebo infusion in the two individuals receiving this therapy. In
      contrast, ADL 10-0101 infusion reduced pain score from 63+/-7.6 (mean+/-SE) prior
      to infusion to 23+/-15 4h after infusion (P<0.05 vs. baseline). One patient
      receiving placebo and one receiving ADL 10-0101 experienced a mild headache
      during the study. One patient receiving ADL 10-0101 experienced restlessness and
      another had assymptomatic transient dysrhythmia upon standing after the 4h study.
      Neither of the treatments affected blood pressure, heart rate, respiratory rate,
      or oxyhemoglobin saturation, and no patient experienced nausea during the study.
      These limited data support the hypothesis that human visceral afferents express
      KOR and that peripherally restricted KOR agonists produce analgesia in patients
      with chronic visceral pain.

PMID- 12507704
TI  - Thalamic field potentials in chronic central pain treated by periventricular gray
      stimulation -- a series of eight cases.
AB  - Chronic deep brain stimulation (DBS) of the periventricular gray (PVG) has been
      used for the treatment of chronic central pain for decades. In recent years motor
      cortex stimulation (MCS) has largely supplanted DBS in the surgical management of
      intractable neuropathic pain of central origin. However, MCS provides
      satisfactory pain relief in about 50-75% of cases, a range comparable to that
      reported for DBS (none of the reports are in placebo-controlled studies and hence
      the further need for caution in evaluating and comparing these results). Our
      experience also suggests that there is still a role for DBS in the control of
      central pain. Here we present a series of eight consecutive cases of intractable
      chronic pain of central origin treated with PVG DBS with an average follow-up of
      9 months. In each case, two electrodes were implanted in the PVG and the
      ventroposterolateral thalamic nucleus, respectively, under guidance of corneal
      topography/magnetic resonance imaging image fusion. The PVG was stimulated in the
      frequency range of 2-100 Hz in alert patients while pain was assessed using the
      McGill-Melzack visual analogue scale. In addition, local field potentials (FPs)
      were recorded from the sensory thalamus during PVG stimulation. Maximum pain
      relief was obtained with 5-35 Hz stimulation while 50-100 Hz made the pain worse.
      This suggests that pain suppression was frequency dependent. Interestingly, we
      detected low frequency thalamic FPs at 0.2-0.4 Hz closely associated with the
      pain. During 5-35 Hz PVG stimulation the amplitude of this potential was
      significantly reduced and this was associated with marked pain relief. At the
      higher frequencies (50-100 Hz), however, there was no reduction in the FPs and no
      pain suppression. We have found an interesting and consistent correlation between
      thalamic electrical activity and chronic pain. This low frequency potential may
      provide an objective index for quantifying chronic pain, and may hold further
      clues to the mechanism of action of PVG stimulation. It may be possible to use
      the presence of these slow FPs and the effect of trial PVG DBS on both the
      clinical status and the FPs to predict the probable success of future pain
      control in individual patients.

PMID- 12507705
TI  - Powerful antinociceptive effects of the cone snail venom-derived subtype
      selective NMDA receptor antagonists conantokins G and T.
AB  - Subunit non-selective N-methyl-D-aspartate (NMDA) receptor antagonists reduce
      injury-induced pain behavior, but generally produce unacceptable side effects. In
      this study, we examined the antinociceptive and motor effects of cone snail venom
      derived peptides, conantokins G and T (conG and conT), which are selective
      inhibitors of the NR2B or NR2A and NR2B subtypes of the NMDA receptor,
      respectively. We tested the effects of conG and conT in models of tissue
      (formalin test), nerve injury (partial sciatic nerve ligation) and inflammation
      induced (intraplantar Complete Freund's Adjuvant; CFA) pain in mice. In the
      formalin test, intrathecal (i.t.) conG or conT suppressed the ongoing pain
      behavior (ED(50) and 95% confidence intervals (CI), 11 (7-19) and 19 (11-33),
      respectively) at doses that were 17-27 times lower than those required to impair
      motor function (accelerating rotarod treadmill test: ED(50) and 95% CI, 300 (120
      730) and 320 (190-540) pmol, respectively). By comparison, SNX-111, an N-type
      voltage-sensitive calcium channel antagonist that is also derived from cone snail
      venom, produced significant motor impairment at a dose (3.0 pmol, i.t.) that was
      only partially efficacious in the formalin test. Furthermore, conG reversed the
      allodynia produced by nerve injury, with greater potency on thermal (ED50 and 95%
      CI, 24 (10-55) pmol) than on mechanical allodynia (59 (33-105) pmol). Finally, a
      single dose of conG (100 pmol, i.t.) also reduced CFA-evoked thermal and
      mechanical allodynia. Taken together, these results demonstrate that conantokins
      exhibit potent antinociceptive effects in several models of injury-induced pain.
      The study supports the notion that drugs directed against subtypes of the NMDA
      receptor, by virtue of their reduced side-effect profile, hold promise as novel
      therapeutic agents for the control of pain.

PMID- 12507706
TI  - Functional plasticity in the human primary somatosensory cortex following acute
      lesion of the anterior lateral spinal cord: neurophysiological evidence of short
      term cross-modal plasticity.
AB  - The primary somatosensory cortex (S1) in adult animals and humans is capable of
      rapid modification after deafferentation. These plastic changes may account for a
      loss of tonic control by nociceptive inputs over inhibitory mechanisms within
      structures of the dorsal column-medial lemniscal system. Most studies, however,
      have been performed under conditions where deafferentation of C and A delta
      fibres coexists with large-diameter fibres deafferentation. In this study the
      effect of the acute lesion of one ascending anterior lateral column on neuronal
      activity within the dorsal column-medial lemniscal system was assessed by
      recording somatosensory evoked potentials (SEPs) in seven patients who underwent
      unilateral percutaneous cervical cordotomy (PCC) as treatment for drug-resistant
      malignant pain.Spinal, brainstem and cortical SEPs were recorded 2h before and 3h
      after PCC by stimulating the posterior tibial nerve at both ankles. Amplitudes of
      cortical potentials obtained by stimulation of the leg contralateral to PCC were
      significantly increased after PCC. No significant changes in spinal or brainstem
      potentials were observed. PCC did not affect SEP components obtained by
      stimulation of the leg ipsilateral to PCC. Our results suggest that nociceptive
      deafferentation may induce a rapid modulation of cortical neuronal activity along
      the lemniscal pathway, thus providing the first evidence in humans of short-term
      cortical plasticity across the spinothalamic and lemniscal systems.

PMID- 12507707
TI  - Characterization of the analgesic actions of adenosine: comparison of adenosine
      and remifentanil infusions in patients undergoing major surgical procedures.
AB  - Perioperative pain is still a major problem, and new pharmacological means should
      be explored to mitigate such pain. Adenosine is an ubiquitous endogenous
      substance; when exogenously administered, it provides a number of salutary
      effects including neuromodulation, antinociception, and cytoprotective actions.
      The aim of this study was to characterize the perioperative antinociceptive
      analgesic effects of intraoperative adenosine infusion and determine the duration
      of actions in the postoperative period, and compare them to those of remifentanil
      in patients undergoing major surgical procedures in a double-blind study.Sixty
      two patients were randomly assigned to one of the two treatments. After standard
      induction of anesthesia, the lungs were mechanically ventilated. Anesthesia was
      maintained with a constant alveolar concentration of inhaled anesthetics (3%
      desflurane and 65% nitrous oxide in oxygen). A variable-rate of intravenous
      infusion of adenosine (50-500 microg kg(-1) x min(-1)) or remifentanil (0.05-0.5
      microg kg(-1) x min(-1)) was initiated 5 min before the skin incision and was
      titrated to maintain systolic blood pressure and heart rate within 20% of
      baseline values during surgery. Postoperative evaluations included the level of
      sedation, degree of pain severity, opioid analgesic (fentanyl, morphine)
      consumption, and cardiorespiratory variables for 48 h. Intraoperative inhibition
      of the cardiovascular responses to surgical stimulation could be equally achieved
      by adenosine or remifentanil, and both could maintain excellent hemodynamic
      stability. Postoperatively, however, there were striking differences: (1).
      initial pain score was reduced by 60% (P<0.001) in the adenosine group compared
      to the remifentanil group and it remained lower throughout the 48 h recovery
      period; (2). postoperative morphine requirements during the first 0.25, 2 and 48
      h were consistently lower in the adenosine group as compared to the remifentanil
      group (78, 71 and 42%, P<0.001, respectively); (3). adenosine patients remained
      significantly less sedated at all evaluations; (4) the end-tidal and arterial
      carbon dioxide values in the remifentanil group were significantly higher when
      patients were admitted to the postanesthesia care unit. No adverse effect of
      adenosine was observed at any time. Intraoperative adenosine infusion provided a
      salutary recovery from anesthesia associated with a pronounced and sustained
      postoperative pain relief. Compared to remifentanil, adenosine significantly
      reduced the opioid requirements and minimized the side effects including
      protracted sedation, cardiorespiratory instability, nausea, and vomiting in the
      postoperative recovery period.

PMID- 12507708
TI  - Spinal nerve injury activates prostaglandin synthesis in the spinal cord that
      contributes to early maintenance of tactile allodynia.
AB  - To determine if spinal prostaglandins (PG) contribute to tactile allodynia, male,
      Sprague-Dawley rats were fitted with either intrathecal (i.t.) microdialysis or
      drug delivery catheters 3 days before tight ligation of the left lumber 5/6
      spinal nerves. Paw withdrawal thresholds (PWT) were determined using von Frey
      filaments. Ligated rats developed tactile allodynia within 24h, as evidenced by a
      decrease in PWT in the affected hindpaw (<4 g vs. >15 g control). Sham-operated
      controls were unchanged from baseline (>15 g). Allodynia was also characterized
      by a significant increase in the evoked release of PGE(2). Thus, brushing the
      plantar surface of the affected hindpaw with a cotton-tipped applicator, 5 days
      postligation, increased the [PGE(2)](dialysate) to 199+/-34% of the prestimulus
      control period. In contrast, brushing had no detectable effect on release before
      surgery or in sham-operated animals. Basal release (no brushing) was similar
      before and after surgery (sham-operated and ligated rats). In a separate group of
      rats and beginning 2 days after ligation, the acute i.t. injection of S(+)
      ibuprofen, SC-51322, SC-236, or SC-560 significantly reversed allodynia (maximum
      effect=69+/-9, 66+/-6, 57+/-4, 20+/-5%, respectively). R(-)-ibuprofen or vehicle
      were without effect. The results of this study suggest that: (a). spinal PG
      synthesis and allodynia-like behaviour are triggered by normally innocuous
      brushing after spinal nerve ligation; (b). pharmacological disruption of this
      cascade significantly reverses allodynia; (c). COX-2 is the relevant isozyme; and
      (d). the PG effect is mediated by spinal EP receptors.

PMID- 12507709
TI  - Striatal dopamine D1 and D2 receptors in burning mouth syndrome.
AB  - Animal studies have indicated that the nigrostriatal dopaminergic system is
      involved in central pain modulation. In a recent positron emission tomography
      (PET) study, we demonstrated presynaptic dysfunction of the nigrostriatal
      dopaminergic pathway in burning mouth syndrome, which is a chronic pain state.
      The objective of the present study was to examine striatal dopamine D1 and D2
      receptors in these patients. We used 11C-NNC 756 and 11C-raclopride to study D1
      and D2 receptor binding in a PET study in ten burning mouth patients and 11
      healthy controls. Patients underwent a structured psychiatric evaluation and an
      electrophysiological test for the excitability of the blink reflex. The striatal
      uptake of 11C-NNC 756 did not differ between patients and controls. In a voxel
      level analysis, the uptake of 11C-raclopride was statistically significantly
      higher in the left putamen in burning mouth patients (corrected P-value 0.038 at
      cluster-level). In the region of interest analysis, the D1/D2 ratio was 7.7%
      lower in the right putamen (0.64+/-0.04 vs. 0.69+/-0.04, P=0.01) and 6.4 % lower
      in the left putamen (0.65+/-0.05 vs. 0.70+/-0.05, P=0.05) when compared to
      controls. Increased 11C-raclopride uptake and the subsequent decrease in the
      D1/D2 ratio may indicate a decline in endogenous dopamine levels in the putamen
      in burning mouth patients.

PMID- 12507710
TI  - Age-related differences in endogenous pain modulation: a comparison of diffuse
      noxious inhibitory controls in healthy older and younger adults.
AB  - Despite decades of research, hundreds of studies, and a number of recent reviews,
      the effects of aging on the experience of pain remain poorly understood. Many
      prior investigators have reported increases in persistent pain conditions and
      diminished tolerance for certain types of laboratory-induced pain among the
      elderly. While explanations for these effects often propose senescent decrements
      in endogenous analgesic systems as a possible contributory mechanism, almost no
      direct empirical evidence for this hypothesis has yet emerged in human studies.
      The present investigation was designed to evaluate the existence and nature of
      these putative age-related differences in endogenous pain inhibition. Groups of
      healthy younger (n=45, mean age=21.6 years, range=18-25) and older (n=48, mean
      age=63.1 years, range=55-67) adults participated in a controlled, two-session
      laboratory assessment of diffuse noxious inhibitory controls (DNIC), a measure of
      endogenous pain inhibition. In this study, we examined age differences in the
      effects of concurrent cold pain on ratings of heterotopically presented
      repetitive noxious thermal stimuli. Interestingly, older adults demonstrated
      facilitation rather than inhibition of thermal pain during concurrent noxious
      cold stimulation while younger adults demonstrated some expected DNIC effects
      (i.e. a reduction in thermal pain ratings during heterotopic stimulation with
      noxious cold). Collectively, the findings of the present study suggest age
      associated decrements in at least one form of endogenous analgesic response. If
      replicated, such findings of reduced pain-modulatory capacity in the elderly may
      partially explain age-related differences in the prevalence, severity, and impact
      of chronic pain.

PMID- 12507711
TI  - Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second
      pain in normal males but not in normal females or fibromyalgia patients.
AB  - Diffuse noxious inhibitory control (DNIC) is part of a central pain modulatory
      system that relies on spinal and supraspinal mechanisms. Previous studies have
      shown that fibromyalgia (FMS) patients are lacking DNIC effects on experimental
      pain, compared to normal control (NC) subjects. Because DNIC has a greater effect
      on second pain than on first pain, we hypothesized that wind-up (WU) of second
      pain should be attenuated by a strong conditioning stimulus. Thus, we compared
      DNIC's effect on WU in three groups of subjects: 11 NC males, 22 NC females, and
      11 FMS females. To separately assess the contributions of distraction related
      mechanisms to inhibition of second pain, we designed the experiment in such a way
      that directed the subjects' attention to either the test or conditioning
      stimulus. Repeated heat taps to the thenar surface of the right hand were used as
      test stimuli to generate WU of second pain. Immersion of the left hand into a hot
      water bath was the conditioning stimulus. As previous experiments have shown,
      DNIC requires a strong conditioning stimulus for pain attenuation, which may be
      at least partly dependent on a distraction effect. DNIC significantly inhibited
      thermal WU pain in normal male subjects, but adding distraction to the DNIC
      effect did not increase the extent of this inhibition. In contrast, neither DNIC
      nor DNIC plus distraction attenuated thermal WU pain in female NCs. DNIC plus
      distraction but not DNIC alone produced significant inhibition of thermal WU pain
      in female FMS patients. Our results indicate that DNIC effects on experimental WU
      of second pain are gender specific, with women generally lacking this pain
      inhibitory mechanism.

PMID- 12507712
TI  - Tumor implantation in mouse humerus evokes movement-related hyperalgesia
      exceeding that evoked by intramuscular carrageenan.
AB  - In this paper we compare two innovative models of movement-related pain: tumor
      induced nociception following implantation of fibrosarcoma cells into bone and
      muscle inflammation-induced nociception following injection of the irritant
      carrageenan into muscle. Importantly, using the grip force test, an assay of
      movement-related hyperalgesia, both non-malignant and malignant pain are examined
      in parallel. Movement-related hyperalgesia, known clinically as a specific type
      of 'breakthrough pain', is a common feature of bone cancer and is thought to be a
      predictor of poor response to conventional analgesic pharmacotherapy (Bruera et
      al., 1995, J. Pain Symptom. Manage. 10 (1995) 348; Mercadaute et al., 1992, Pain
      50 (1992) 151; Pain 81 (1999) 129). Implantation of NCTC 2472 sarcoma cells in
      both humeri or injection of carrageenan (4%) in both triceps of C3H/He mice
      produced apparent forelimb hyperalgesia that was not associated with mechanical
      hyperalgesia in the forepaw, whereas carrageenan at 6 and 8% did evoke
      significant cutaneous hyperalgesia of the forepaw as well. Control groups
      receiving implants of vehicle or no treatment at all did not manifest this
      forelimb hyperalgesia. B6C3/F1 mice implanted with non-lysis-inducing G3.26
      melanoma cells or vehicle did not manifest significant hyperalgesia when compared
      to B6C3/F1 mice receiving fibrosarcoma cells, indicating a dependence on bone
      involvement for induction of hyperalgesia in this model. Histological examination
      at days 3, 7, and 10 post-implantation showed a clear correlation of tumor growth
      induced bone destruction with behavioral hyperalgesia. Morphine was more potent
      in decreasing the maximal hyperalgesia induced by carrageenan than that induced
      by tumor implantation. Acutely administered morphine (3-100mg/kg, i.p.)
      attenuated peak hyperalgesia of carrageenan-injected mice (ED(50) 6.9 mg/kg) and
      tumor-bearing mice (ED(50) 23.9 mg/kg) in a dose-related manner with a difference
      in potency of 3.5. Tumor-implanted mice with a level of hyperalgesia comparable
      to that induced by carrageenan required almost three times more morphine (ED(50)
      18.5mg/kg) for equivalent attenuation of forelimb hyperalgesia. These animal
      models of movement-related hyperalgesia may aid in discerning the peripheral and
      central mechanisms underlying pain that accompanies bone metastases and
      distinguishing it from the pain associated with muscular inflammation.
      Importantly, they may also aid in predicting differences in analgesic efficacy in
      different types of musculoskeletal pain.

PMID- 12507713
TI  - Pain phenomena and possible mechanisms in patients with painful polyneuropathy.
AB  - Painful polyneuropathy is a common neuropathic pain condition characterized by
      different typical pain phenomena and symptoms. The present study determined the
      frequency of pain phenomena and signs in painful polyneuropathy, and compared the
      symptomatology in patients with signs of increased small fiber response with that
      in patients with signs of deafferentation. Eighty-one consecutive patients with
      painful polyneuropathy were studied. The most common pain phenomena were deep
      aching pain (88%) and pain on pressure (69%), followed by pain paroxysms (59%)
      and less frequently pain on light touch (31%). Patients with increased cold and
      heat detection thresholds were more likely to have pain paroxysms (odds ratio
      (OR) 2.5 and 5.2) and patients with pain summation on repetitive mechanical
      stimulation more often had touch-evoked pain (OR=4.0) than patients without these
      phenomena. Findings compatible with increased small fiber response were found in
      six patients (7.4%), in 41 (50.6%) unequivocal signs of deafferentation were
      found, and 34 patients (42%) could not be classified. There was no significant
      difference in presenting symptoms between these groups. In conclusion, in painful
      polyneuropathy, (1). deep aching pain is the most frequently reported pain
      symptom; (2). the association between pain paroxysms with decreased small fiber
      function and touch-evoked pain with abnormal pain summation on mechanical
      stimulation indicate that central nervous system mechanisms are responsible for
      these symptoms; (3). sensitized small fibers as the single mechanism of pain is
      rare; and (4). pain symptomatology cannot predict pain mechanisms as being mainly
      deafferentation or sensitized small fibers.

PMID- 12507714
TI  - Immediate- or sustained-release morphine for dose finding during start of
      morphine to cancer patients: a randomized, double-blind trial.
AB  - A titration procedure using immediate-release morphine given 4-hourly is
      recommended during start of oral morphine for cancer pain. This recommendation is
      not based on evidence from controlled studies, and many physicians start morphine
      treatment with controlled-release morphine. We included 40 patients with
      malignant disease and pain despite treatment with opioids for mild to moderate
      pain in a randomized, double-blind, double-dummy, parallel-group study comparing
      titration with immediate-release morphine given 4-hourly with titration with
      sustained-release morphine given once daily. The primary end point was the time
      needed to achieve adequate pain relief Secondary end points were other symptoms
      (nausea, tiredness, lack of sleep, vertigo, appetite and constipation), health
      related quality of life and patient satisfaction. The mean times needed for
      titration were 2.1 (95% CI; 1.4-2.7) days using immediate-release morphine and
      1.7 (95% CI; 1.1-2.3) days using sustained-release morphine. Patients titrated
      with immediate-release reported statistically significant more tiredness at the
      end of titration. We observed no other differences in adverse effects or health
      related quality of life functions between the two treatments. Similar global
      satisfactions with the morphine treatments were reported. In conclusion, a
      simplified titration using sustained-release morphine once daily is equally
      effective as immediate-release morphine given 4-hourly.

PMID- 12507715
TI  - Up-regulation and trafficking of delta opioid receptor in a model of chronic
      inflammation: implications for pain control.
AB  - Pharmacological and physiological evidence supports a role for delta (delta)
      opioid receptors in the nociceptive mechanisms of inflammation. However, few data
      exist regarding delta opioid receptor expression and localization in such
      conditions. In this study, we have assessed the distribution and function of
      delta opioid receptors in the rat spinal cord following induction of chronic
      inflammation by intraplantar injection of complete Freund's adjuvant (CFA).
      Intrathecal administration of the selective delta opioid receptor agonist, D
      [Ala(2), Glu(4)] deltorphin, dose-dependently reversed thermal hyperalgesia
      induced by CFA. In situ hybridization and Western blotting experiments revealed
      an increase in delta opioid receptor mRNA and protein levels, respectively, in
      the dorsal lumbar spinal cord ipsilateral to the CFA injection site compared to
      the contralateral side and sham-injected controls. By electron microscopy,
      immunopositive delta opioid receptors were evident in neuronal perikarya,
      dendrites, unmyelinated axons and axon terminals. Quantification of
      immunopositive signal in dendrites revealed a twofold increase in the number of
      immunogold particles in the ipsilateral dorsal spinal cord of CFA-injected rats
      compared to the contralateral side and to sham-injected rats. Moreover, the
      relative frequency of immunogold particles associated with or in close proximity
      to the plasma membrane was increased in the ipsilateral dorsal spinal cord,
      indicating a more efficient targeting of delta opioid receptors to neuronal
      plasma membranes. These data demonstrate that CFA induces an up-regulation and
      increased membrane targeting of delta opioid receptors in the dorsal spinal cord
      which may account for the enhanced antinociceptive effects of delta opioid
      receptor agonists in chronic inflammatory pain models.

PMID- 12507716
TI  - The combination of low dose of naloxone and morphine in patient-controlled (PCA)
      does not decrease opioid requirements in the postoperative period.

PMID- 12507718
TI  - Cell permeable ROS scavengers, Tiron and Tempol, rescue PC12 cell death caused by
      pyrogallol or hypoxia/reoxygenation.
AB  - The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive
      oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3
      benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at
      concentrations, which evidently increased intracellular O(2)*-, as assessed by
      O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors,
      Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by
      elevation of intracellular O(2)*-, although these inhibitors had effects on
      hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*
      scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4
      hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol
      induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked
      by Tiron and Tempol. Further understanding of the underlying mechanism of the
      protective effects of these radical scavengers reducing intracellular O(2)*- on
      neuronal cell death may lead to development of new therapeutic treatments for
      hypoxic/ischemic brain injury.

PMID- 12507719
TI  - Convergence of gastric vagal and cerebellar fastigial nuclear inputs on glycemia
      sensitive neurons of lateral hypothalamic area in the rat.
AB  - Gastric vagal and cerebellar fastigial nuclear afferents have been implicated in
      the regulation of food intake by their communication with lateral hypothalamic
      area (LHA), which is generally referred to be the feeding center. This study was
      designed to examine the possible convergence of the inputs from the gastric vagal
      trunks and cerebellar fastigial nucleus (FN) on the LHA neurons. Among recorded
      191 LHA neurons, 99 (51.8%) responded to the stimulation of the gastric vagal
      trunks, of which 55 (55.6%) also responded to the cerebellar FN stimulation. Of
      62 LHA neurons that responded to the gastric vagal stimulation, 43 (69.4%) showed
      an inhibitory response to the intravenous glucose application indicating they
      were glycemia-sensitive neurons. When the gastric vagal trunks and cerebellar FN
      were stimulated simultaneously, a summation of the responses usually could be
      seen in the recorded LHA neurons (16/20, 80%). Moreover, of 45 LHA neurons that
      responded to both of the gastric vagal trunks and FN stimuli, 30 (66.7%) were
      identified to be glycemia-sensitive neurons. These results demonstrated that
      gastric vagal afferents could reach glycemia-sensitive neurons of the LHA, and
      that the inputs from cerebellar FN and gastric vagal trunks could converge onto
      glycemia-sensitive neurons in the LHA. According to the facts that gastric vagal
      inputs and blood glucose level may transmit meal-related visceral signals and FN
      may forward the somatic information to the LHA, we suggest that an integration of
      the somatic-visceral response related to the food intake may take place in the
      LHA following the gastric vagal and cerebellar FN afferent inputs and the
      integration may play an important role in the short-term regulation of feeding
      behavior.

PMID- 12507720
TI  - Haloperidol reduces the sympathetic and thermogenic activation induced by orexin
      A.
AB  - This experiment tested the effect of haloperidol on the sympathetic and
      thermogenic effects induced by orexin A. The firing rates of the sympathetic
      nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic
      temperatures and heart rate were monitored in urethane-anesthetized male Sprague
      Dawley rats before and 5 h after an injection of orexin A (1.5 nmol) into the
      lateral cerebral ventricle. The same variables were monitored in rats with an
      intraperitoneal administration of haloperidol (1 mg/kg bw), a D(2) receptor
      antagonist. The results show that orexin A increases the sympathetic firing rate,
      IBAT and colonic temperatures and heart rate. This increase is reduced by the
      haloperidol. These findings suggest that dopaminergic system is activated during
      the orexin A-induced hyperthermia.

PMID- 12507721
TI  - Amyloid beta protein enhances the clearance of extracellular L-glutamate by
      cultured rat cortical astrocytes.
AB  - To explore the impact of Alzheimer's disease amyloid beta protein (Abeta) on
      astrocyte functions, we investigated the effect of Abeta on glutamate clearance
      capacity of cultured rat cortical astrocytes. When L-glutamate (50-200 microM)
      was added to astrocyte cultures and incubated, the extracellular L-glutamate
      concentration declined with time. The time-dependent decline of extracellular L
      glutamate was significantly faster in cultures treated with 10-20 microM Abeta
      for 24 h than in intact cultures, suggesting that Abeta enhances the L-glutamate
      clearance capacity of astrocytes. The effect of Abeta was not affected by
      antioxidants including catalase, propyl gallate or Trolox. Relatively long
      treatment time (8-48 h) was required for Abeta to exert this effect. Western blot
      analysis revealed that expression level of the glutamate transporter GLAST was
      increased by treatment with 10-20 microM Abeta for 8-48 h. These results suggest
      that Abeta upregulates a glutamate uptake system of astrocytes and enhances the
      clearance of extracellular L-glutamate.

PMID- 12507722
TI  - Intramuscular injection of AAV-GDNF results in sustained expression of transgenic
      GDNF, and its delivery to spinal motoneurons by retrograde transport.
AB  - Adeno-associated virus (AAV) vector has been developed as an attractive gene
      delivery system with proven safety. Glial cell line-derived neurotrophic factor
      (GDNF) is proposed to be a promising therapeutic agent for amyotrophic lateral
      sclerosis (ALS) and other motor neuron diseases. The purpose of this report was
      to investigate transgenic GDNF expression at different time points post AAV
      mediated GDNF intramuscular delivery. An AAV vector was constructed to encode a
      recombinant fusion of GDNF tagged with a FLAG sequence at the C-terminal (AAV
      GDNF) to distinguish it from its endogenous counterpart. A single intramuscular
      injection of AAV-GDNF led to substantial expression of transgenic GDNF which
      remained for at least 10 months in transduced gastrocnemius muscle. This
      transgenic GDNF was distributed in a large number of myofibers, mainly in the
      vicinity of the sarcolemma and predominantly concentrated at the sites of
      neuromuscular junctions (NMJs). Furthermore, transgenic GDNF, but not beta
      galactosidase expressed as a control, was detected in the motoneurons that
      projected axons to the injected muscles, thus, indicating retrograde axonal
      transportation of the transgenic GDNF. This study provides a basis for a strategy
      of intramuscular AAV-GDNF delivery to protect motoneurons as a possible means of
      ALS treatment.

PMID- 12507723
TI  - Brainstem and spinal projections of augmenting expiratory neurons in the rat.
AB  - There are two types of expiratory neurons with augmenting firing patterns (E-AUG
      neurons), those in the Botzinger complex (BOT) and those in the caudal ventral
      respiratory group (cVRG). We studied their axonal projections morphologically
      using intracellular labeling of single E-AUG neurons with Neurobiotin, in
      anesthetized, paralyzed and artificially-ventilated rats. BOT E-AUG neurons (n =
      11) had extensive axonal projections to the brainstem, but E-AUG neurons (n = 5)
      of the cVRG sent axons that descended the contralateral spinal cord without
      medullary collaterals. In addition to these somewhat expected characteristics,
      the present study revealed a number of new projection patterns of the BOT E-AUG
      neurons. First, as compared with the dense projections to the ipsilateral
      brainstem, those to the contralateral side were sparse. Second, several BOT E-AUG
      neurons sent long ascending collaterals to the pons, which included an axon that
      reached the ipsilateral parabrachial and Kolliker-Fuse nuclei and distributed
      boutons. Third, conspicuous projections from branches of these ascending
      collaterals to the area dorsolateral to the facial nucleus were found. Thus, the
      present study has shown an anatomical substrate for the extensive inhibitory
      projections of single BOT E-AUG neurons to the areas spanning the bilateral
      medulla and the pons.

PMID- 12507724
TI  - Effects of sleep on pain-related somatosensory evoked potentials in humans.
AB  - We investigated effects of sleep on pain-related somatosensory evoked potentials
      (SEP) following painful electrical stimulation of the left index finger. The
      biggest advantage of this method is that signals ascending through both A-beta
      fibers relating to touch and A-delta fibers relating to pain can be recorded
      simultaneously. While the subject was awake, non-painful stimulation evoked early
      and middle latency components, N20, P30 and N60, at the C4 electrode, and
      painful stimulation evoked not only early- and middle latency components at the
      C4 but also later pain-specific components, N130 and P240, at the Cz electrode.
      During sleep, N20 and P30 did not show a significant change in amplitude, N60
      showed a slight but significant amplitude reduction, and N130 and P240
      significantly decreased in amplitude or disappeared, as compared with those while
      awake. Therefore, we speculate on the mechanisms generating each component as
      follows; (1) N20 and P30 are the primary components generated in SI ascending
      through A-beta fibers. (2) N60 is the secondary component generated in SI
      involving cognitive function to some degree. (3) N130-P240 are the pain-specific
      components ascending through A-delta fibers, and closely related to cognitive
      function, because they were much affected by consciousness, different from the
      components ascending through A-beta fibers.

PMID- 12507725
TI  - Primary structure, functional characterization and developmental expression of
      the ascidian Kv4-class potassium channel.
AB  - Ascidians belong to the primitive chordates and their larvae show symmetrical
      beating of the tail, which is reminiscent of the swimming pattern in primitive
      vertebrates. Since ascidian larva contains only a small number of neurons in
      their entire larval nervous system, they will potentially provide a simple model
      for the study of animal locomotion. In a step towards the goal of establishing
      the molecular basis underlying ascidian larval neurophysiology, we describe here
      a Kv4 class of voltage-gated potassium channel, TuKv4, from Halocynthia roretzi.
      Whole mount in situ hybridization indicates that TuKv4 is expressed in most of
      larval neurons including motor neurons. TuKv4-currents reconstituted in Xenopus
      oocytes show currents with similar properties to the lower-threshold A-type
      currents from cleavage-arrested ascidian blastomeres of neural lineage. However,
      the voltage-dependency of the steady-state inactivation and activation was
      shifted leftward by 20 mV, as compared with native A-type currents, suggesting
      that other components may be required to restore full function of the Kv4
      channel. Unexpectedly, another isoform lacking C-terminal cytoplasmic region was
      also isolated. This truncated isoform did not lead to a functional current in
      Xenopus oocytes. RT-PCR analysis showed that the truncated form is transiently
      expressed during larval development, suggesting some developmental role for
      potassium channel expression.

PMID- 12507726
TI  - Parieto-frontal networks for clock drawing revealed with fMRI.
AB  - We studied the neural substrates of clock drawing using functional magnetic
      resonance imaging in 18 right-handed volunteers. In the test condition, subjects
      were required to draw the hands of a clock corresponded to the time presented
      acoustically. In the control task, they drew horizontal and vertical lines after
      reciting silently the numerals of three figures presented acoustically. In group
      analyses, comparison between the test and control condition revealed brain areas
      related to clock drawing; bilateral posterior parietal cortices with a right side
      dominance, bilateral dorsal premotor areas, the left pre-supplementary motor
      area, the left ventral prefrontal cortex, the left precentral gyrus, and
      bilateral cerebellum. In particular, the posterior parietal cortex and the dorsal
      premotor area, which were strongly activated in all 18 subjects examined in
      individual analyses, appear to be the main constituent of the parieto-frontal
      cortical networks for clock drawing.

PMID- 12507727
TI  - Thr123 of rat G-substrate contributes to its action as a protein phosphatase
      inhibitor.
AB  - Rat G-substrate cDNA was isolated from a cerebellar library and characterized.
      The deduced amino acid sequence of rat G-substrate contained two putative
      phosphorylation sites for PKG at Thr72 and Thr123; the amino acid sequences
      (KPRRKDT(p)PA) around these sites are conserved in human, mouse and rabbit. G
      substrate phosphorylated by PKG inhibited the catalytic subunits of both protein
      phosphatase-1 (IC(50) 14.1 nM) and -2A (IC(50) 5.9 nM). Mutation of Thr123 (site
      2) to Ala significantly reduced the inhibition of both PP-1 and PP-2A, while
      mutation of Thr72 (site 1) to Ala had little effect on inhibitory activity. In
      situ hybridization analysis revealed that G-substrate mRNA was localized
      exclusively in cerebellar Purkinje cells. Immunoperoxidase staining showed that
      in Purkinje cells, G-substrate was present in somata, dendrites and axons. In rat
      cerebellar slices, activation of PKG with a nitric oxide (NO) donor, NOR3, or 8
      Br-cGMP, increased phosphorylation of G-substrate, as demonstrated with a
      phosphorylation-specific antibody. These results characterize further the
      inhibition of PP-1 and PP-2A by phospho-G-substrate, and demonstrate its
      physiological phosphorylation in rat Purkinje cells.

PMID- 12507728
TI  - Temporal and spatial changes of free cholesterol and neutral lipids in rat brain
      after transient middle cerebral artery occlusion.
AB  - In order to examine lipid metabolism in relation to neural process following
      brain ischemia, we investigated temporal and spatial changes of free cholesterol
      (FC) and neutral lipids (NLs) after 90 min of transient middle cerebral artery
      occlusion (MCAO). Filipin and Nile Red stainings were performed to detect mainly
      FC and NLs, respectively. Double stainings for Nile Red plus ED1, MAP2, or GFAP
      were performed in order to identify cell type of positive stainings. Filipin
      stanining decreased during 1-7 day and lost at 21 day after transient MCAO in the
      ischemic core, but did not change in the penumbra. Nile Red positive droplets
      reached the maximum at 7 day after transient MCAO and gradually decreased in the
      core, while the peak time delayed in the penumbra. MAP2 immunoreactivity lost at
      7 day in the core, and increased in the penumbra during 7-56 day. Most Nile Red
      positive droplets were double positive for ED1 in the core, and were localized
      within GFAP positive cells in the penumbra. These results suggest that changes of
      FC and NLs are different temporally and spatially between the core and penumbra
      in relation to degenerative and regenerative neural processes following brain
      ischemia.

PMID- 12507729
TI  - Characterization of pre- and post-synaptic metabotropic glutamate receptor
      mediated inhibitory responses in substantia nigra dopamine neurons.
AB  - Two inhibitory responses mediated by both pre- and post-synaptic metabotropic
      glutamate receptors (mGluRs) were investigated in dopamine neurons of the
      substantia nigra using whole-cell patch recordings. (2R,4R)-APDC, a group II
      mGluR agonist, and L-2-amino-4-phosphonobutyrate (L-AP4), a group III mGluR
      agonist, reversibly suppressed the amplitude of excitatory postsynaptic currents
      (EPSCs). However, (S)-3,5-DHPG, a group I mGluR agonist, exhibited less
      inhibitory action on the EPSCs. LY341495, a highly potent group II mGluR
      antagonist, antagonized the broad spectrum mGluR agonist, 1S,3R-ACPD-induced
      suppression of EPSCs. In acutely dissociated dopamine neurons, glutamate (Glu) in
      the presence of CNQX and AP-5 evoked an outward current accompanied by an
      increase in K(+) conductance. (S)-3,5-DHPG, but not (2R,4R)-APDC or L-AP4, also
      induced an outward current. Glu-induced outward current (I(Glu-out)) was
      partially inhibited by LY367385, a selective mGluR1 antagonist, but not by MPEP,
      a selective mGluR5 antagonist. Ryanodine and cyclopiazonic acid blocked the I(Glu
      out). In the presence of caffeine, Glu failed to induce a current. Charybdotoxin,
      but not apamin or iberiotoxin, inhibited the I(Glu-out). Taken together, both
      group II and III mGluRs are mainly involved in the presynaptic inhibition of Glu
      release to dopamine neurons, while group I mGluRs, including at least mGluR1,
      participate in the hyperpolarization of dopamine neurons mediated by the opening
      of charybdotoxin-sensitive Ca(2+)-activated K(+) channels.

PMID- 12507730
TI  - Involvement of oxidative stress in the enhancement of acetylcholinesterase
      activity induced by amyloid beta-peptide.
AB  - Acetylcholinesterase (AChE) activity is increased within and around amyloid
      plaques, which are present in Alzheimer's disease (AD) patient's brain. In this
      study, using cultured retinal cells as a neuronal model, we analyzed the effect
      of the synthetic peptide Abeta(25-35) on the activity of AChE, the degradation
      enzyme of acetylcholine, as well as the involvement of oxidative stress in this
      process. The activity of AChE was increased when retinal cells were incubated
      with Abeta(25-35) (25 microM, 24 h) and antioxidants such as alpha-tocopherol
      acetate and nitric oxide synthase (NOS) inhibitors were capable of preventing
      this effect. Despite Abeta(25-35) did not affect cell membrane integrity, the
      redox capacity of cells decreased. The incubation with this amyloidogenic peptide
      led to an increment of reactive oxygen species formation (20%), of lipid
      peroxidation (65%), and basal intracellular calcium levels (40%). The data
      obtained show that the enhancement of AChE activity induced by Abeta(25-35) is
      mediated by oxidative stress, and that vitamin E and NOS inhibitors, by
      preventing the compromise of the enzyme activity, can have an important role in
      the maintenance of acetylcholine synaptic levels, thus preventing or improving
      cognitive and memory functions of AD patients.

PMID- 12507731
TI  - Human skeletal muscle calcium channel alpha1S is expressed in the basal ganglia:
      distinctive expression pattern among L-type Ca2+ channels.
AB  - Voltage-gated calcium channels (VGCCs) are essential molecules for neuronal
      function. VGCCs consist of five subunits, alpha1, alpha2, beta, gamma, and delta.
      Among the ten subtypes of the alpha1 subunit (alpha1A-I and S), expression of
      alpha1S was previously believed to be restricted to the skeletal muscle. We
      report here, however, that alpha1S is also expressed in human and rat central
      nervous system. First, we performed PCR screening for VGCC alpha1 subunits in
      human nervous system using degenerate primers, and identified alpha1S as well as
      all the eight alpha1 subunits with previously described expression. Intriguingly,
      alpha1S was selectively localized to the basal ganglia, particularly the caudate
      nucleus. In situ hybridization showed that alpha1S was expressed in medium-sized
      caudate neurons. Quantitative analysis using real time RT-PCR revealed a distinct
      pattern of alpha1S expression among L-type calcium channels. Furthermore, RT-PCR
      using laser-mediated manipulation of single cells suggested that human alpha1S
      was coexpressed with ryanodine receptors (RYRs) in GABAergic neurons. Our results
      suggest the potential relevance of alpha1S to dopaminergic signal transduction
      and calcium-induced calcium release in caudate neurons.

PMID- 12507732
TI  - Validating 'hard' and 'soft' phenotypes within the bipolar spectrum: continuity
      or discontinuity?
AB  - The unitary Kraepelian concept of manic-depressive illness which incorporated
      attenuated forms, personal dispositions to mood instability, as well as much of
      the terrain of remitting depressions, may be considered by many to be too broad.
      On the other hand, the presently preferred unipolar-bipolar dichotomy in official
      nosology fails to account for the very common occurrence of clinical and
      subclinical conditions in the interface of major depressive disorders and
      bipolarity. The emerging concept of the bipolar spectrum represents a provocative
      working hypothesis to account for these conditions.

PMID- 12507733
TI  - Proposed multidimensional structure of mania: beyond the euphoric-dysphoric
      dichotomy.
AB  - BACKGROUND: Although the construct of depression has been subjected to numerous
      factor analytic studies and phenomenological subtypes of clinical relevance have
      been delineated, this is not the case for mania. The few available studies have
      reported at least two factors, which consist of euphoric versus dysphoric-hostile
      subtypes. Our objective was to replicate and further enrich this literature.
      METHODS: In the EPIMAN French National Study we systematically evaluated 104 DSM
      IV hospitalized manic patients in four university centers in different regions of
      France. Psychiatrists completed the Beigel-Murphy Manic State Rating Scale
      (MSRS), as well as the HAM-D(17), affective temperament scales, and the GAF Axis
      V from DSM-IV. Categorization of patients into pure versus dysphoric mania was
      made on the basis of clinical diagnosis, independent from psychometric measures.
      RESULTS: On principal component analysis of the MSRS, three factors explained the
      largest variance: a global manic (23.3% variance), paranoid-hostile (14.8%
      variance), and psychotic (9.1% variance). After varimax rotation, we obtained
      seven independent factors: F1 Disinhibition-instability, F2 Paranoia-hostility,
      F3 Deficit, F4 Grandiosity-psychosis, F5 Elation-euphoria, F6 Depression, and F7
      (Hyper)sexuality. We could not demonstrate significant correlations between the
      individual factors and impaired functioning on GAF. However, depressive and, to
      some extent, cyclothymic temperaments correlated with F6 Depression. Finally,
      intergroup comparisons between pure versus dysphoric mania diagnosed clinically
      showed high levels of F3 Deficit and F5 Elation in the pure, and of F6 Depression
      in dysphoric, mania; F2 Paranoia-hostility did not discriminate these two
      clinical forms of mania. LIMITATIONS: Although the present analyses on the Beigel
      Murphy represent the largest sample studied to date, they are still underpowered
      and do not guarantee a stable factorial structure. Our findings are cross
      sectional and require prospective validation. CONCLUSIONS: Our data suggest that
      'dysphoria' as used in the literature to qualify mania is insufficiently precise,
      and is best further specified as 'depressive' versus 'irritable.' Moreover, our
      data extend the rich multidimensional phenomenology of mania beyond the existing
      literature: we submit that disinhibition-instability (a core 'activation'
      component) can, on the one hand, be associated with distinct emotional
      presentations (euphoric, depressive, or irritable-hostile), as well as psychotic
      and deficit symptomatology on the other.

PMID- 12507734
TI  - The comparative clinical phenotype and long term longitudinal episode course of
      bipolar I and II: a clinical spectrum or distinct disorders?
AB  - BACKGROUND: The present analyses were designed to compare the clinical
      characteristics and long-term episode course of Bipolar-I and Bipolar-II patients
      in order to help clarify the relationship between these disorders and to test the
      bipolar spectrum hypothesis. METHODS: The patient sample consisted of 135
      definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered
      the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were
      followed systematically for up to 20 years. Groups were compared on demographic
      and clinical characteristics at intake, and lifetime comorbidity of anxiety and
      substance use disorders. Subsets of patients were compared on the number and type
      of affective episodes and the duration of inter-episode well intervals observed
      during a 10-year period following their resolution of the intake affective
      episode. RESULTS: BP-I and BP-II had similar demographic characteristics and ages
      of onset of their first affective episode. Both disorders had more lifetime
      comorbid substance abuse disorders than the general population. BP-II had a
      significantly higher lifetime prevalence of anxiety disorders in general, and
      social and simple phobias in particular, compared to BP-I. Intake episodes of BP
      I were significantly more acutely severe. BP-II patietns had a substantially more
      chronic course, with significantly more major and minor depressive episodes and
      shorter inter-episode well intervals. BP-II patients were prescribed somatic
      treatment a substantially lower percentage of time during and between affective
      episodes. LIMITATIONS: BP-I patients with severe manic course are less likely to
      be retained in long-term follow-up, whereas the reverse might be true for BP-II
      patients who are significantly more prone to depression (i.e., patients with less
      inclination to depression and with good prognosis may have dropped out in greater
      proportions); this could increase the gap in long term course characteristics
      between the two samples. The greater chronicity of BP-II may be due, in part, to
      the fact that the patients were prescribed somatic treatments substantially less
      often both during and between affective episodes. CONCLUSIONS: The variety in
      severity of the affective episodes shows that bipolar disorders, similar to
      unipolar disorders, are expressed longitudinally during their course as a
      dimensional illness. The similarities of the clinical phenotypes of BP-I and BP
      II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They
      are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with
      more severe episodes, and BP-II more chronic with a predominantly depressive
      course), that they are best classified as two separate subtypes in the official
      classification systems.

PMID- 12507735
TI  - Refining the evaluation of bipolar II: beyond the strict SCID-CV guidelines for
      hypomania.
AB  - BACKGROUND: The prevalence of bipolar II disorder in depressed outpatients is
      much higher than previously reported, a finding probably related to systematic
      probing for past hypomania by trained clinicians. Our objective was to further
      refine the strict SCID-CV guidelines for hypomania in depressed outpatients.
      METHODS: 168 consecutive outpatients presenting with major depression were
      systematically interviewed with the SCID-CV about all past hypomanic behavior,
      irrespective of duration and initial negative response to the screening question
      on mood. Once typical hypomanic behaviors were elicited, the patient was re
      questioned about mood change. RESULTS: The prevalence of bipolar II was 61.3%.
      Bipolar II, so-defined, was indistinguishable at age of onset, recurrence, and
      atypical features from a previous sample of 251 BP-II patients interviewed by the
      same clinician (FB) without the present modification of the stem question on
      mood, and which had yielded a prevalence of 45% in the same outpatient clinic.
      LIMITATIONS: Single interviewer, and cross-sectional assessment. CONCLUSIONS:
      Systematic probing for all past hypomanic symptoms and behaviors, independently
      of the answer to the screening question on mood, can elicit hypomanic features
      that would otherwise be discarded by strict adherence to the SCID-CV. A net gain
      of 16% in the diagnosis of BP-II can thereby be achieved.

PMID- 12507736
TI  - Factor structure of hypomania: interrelationships with cyclothymia and the soft
      bipolar spectrum.
AB  - BACKGROUND: No systematic data exists on the phenomenology and psychometric
      aspects of hypomania. In this report we focus on the factor structure of
      hypomania and its relationships with cyclothymic temperament in unipolar (UP) and
      bipolar II (BP-II) spectrum (soft bipolar) patients. METHOD: The combined sample
      of UP and BP-II spectrum patients (n=427) derives from the French National multi
      center study (EPIDEP). The study involved training 48 psychiatrists at 15 sites
      in France in a protocol based on DSM-IV phenomenological criteria for major
      depressive disorder, hypomania, and BP-II, as well as a broadened definition of
      soft bipolarity. Psychometric measures included Angst's Hypomania Checklist (HCA)
      and Akiskal's Cyclothymic Temperament (CT) Questionnaires. RESULTS: In the
      combined sample of the UP and BP-II spectrum, the factor pattern based on the HCA
      was characterized by the presence of one hypomanic component. In the soft bipolar
      group (n=191), two components were identified before and after varimax rotation.
      The first factor (F-1) identified hypomania with positive (driven-euphoric)
      features, and the second factor (F-2) hypomania with greater irritability and
      risk-taking. In exploratory analyses, both factors of hypomania tentatively
      distinguished most soft BP subtypes from UP. However, F-1 was generic across the
      soft spectrum, whereas F-2 was rather specific for II-1/2 (i.e., BP-II arising
      from CT). CT, which was found to conform to a single factor among the soft
      bipolar patients, was significantly correlated only with irritable risk-taking
      hypomania (F-2). LIMITATION: In a study conducted in a clinical setting,
      psychiatrists cannot be kept blind of the data revealed in the various clinical
      evaluations and instruments. However, the systematic collection of all data
      tended to minimize biases. CONCLUSION: EPIDEP data revealed a dual structure of
      hypomania with 'classic' driven-euphoric contrasted with irritable risk-taking
      expressions distributed differentially across the soft bipolar spectrum. Only the
      latter correlated significantly with cyclothymic temperament, suggesting the
      hypothesis that repeated brief swings into hypomania tend to destabilize soft
      bipolar conditions.

PMID- 12507737
TI  - Bipolar II with and without cyclothymic temperament: "dark" and "sunny"
      expressions of soft bipolarity.
AB  - BACKGROUND: In the present report deriving from the French national multi-site
      EPIDEP study, we focus on the characteristics of Bipolar II (BP-II), divided on
      the basis of cyclothymic temperament (CT). In our companion article (Hantouche et
      al., this issue), we found that this temperament in its self-rated version
      correlated significantly with hypomanic behavior of a risk-taking nature. Our aim
      in the present analyses is to further test the hypothesis that such patients
      assigned to CT on the basis of clinical interview-represent a more "unstable"
      variant of BP-II. METHODS: From a total major depressive population of 537
      psychiatric patients, 493 were re-examined on average a month later; after
      excluding 256 DSM-IV MDD and 41 with history of mania, the remaining 196 were
      placed in the BP-II spectrum. As mounting international evidence indicates that
      hypomania associated with antidepressants belongs to this spectrum, such
      association per se did not constitute a ground for exclusion. CT was assessed by
      clinicians using a semi-structured interview based on in its French version; as
      two files did not contain full interview data on CT, the critical clinical
      variable in the present analyses, this left us with an analysis sample of 194 BP
      II. Socio-demographic, psychometric, clinical, familial and historical parameters
      were compared between BP-II subdivided by CT. Psychometric measures included self
      rated CT and hypomania scales, as well as Hamilton and Rosenthal scales for
      depression. RESULTS: BP-II cases categorically assigned to CT (n=74) versus those
      without CT (n=120), were differentiated as follows: (1). younger age at onset
      (P=0.005) and age at seeking help (P=0.05); (2). higher scores on HAM-D (P=0.03)
      and Rosenthal (atypical depressive) scale (P=0.007); (3). longer delay between
      onset of illness and recognition of bipolarity (P=0.0002); (4). higher rate of
      psychiatric comorbidity (P=0.04); (5). different profiles on axis II (i.e., more
      histrionic, passive-aggressive and less obsessive-compulsive personality
      disorders). Family history for depressive and bipolar disorders did not
      significantly distinguish the two groups; however, chronic affective syndromes
      were significantly higher in BP-II with CT. Finally, cyclothymic BP-II scored
      significantly much higher on irritable-risk-taking than "classic" driven-euphoric
      items of hypomania. CONCLUSION: Depressions arising from a cyclothymic
      temperament-even when meeting full criteria for hypomania-are likely to be
      misdiagnosed as personality disorders. Their high familial load for affective
      disorders (including that for bipolar disorder) validate the bipolar nature of
      these "cyclothymic depressions." Our data support their inclusion as a more
      "unstable" variant of BP-II, which we have elsewhere termed "BP-II 1/2." These
      patients can best be characterized as the "darker" expression of the more
      prototypical "sunny" BP-II phenotype. Coupled with the data from our companion
      paper (Hantouche et al., 2003, this issue), the present findings indicate that
      screening for cyclothymia in major depressive patients represents a viable
      approach for detecting a bipolar subtype that could otherwise be mistaken for an
      erratic personality disorder. Overall, our findings support recent international
      consensus in favoring the diagnosis of cyclothymic and bipolar II disorders over
      erratic and borderline personality disorders when criteria for both sets of
      disorders are concurrently met.

PMID- 12507738
TI  - The dual factor structure of self-rated MDQ hypomania: energized-activity versus
      irritable-thought racing.
AB  - BACKGROUND: Bipolar II is diagnosed in a clinically depressed patient by
      documenting history of hypomania. Therefore, it is of great significance for both
      clinical and research purposes to characterize the factor structure of hypomania.
      METHODS: Among consecutive depressive outpatients-126 major depressives and 187
      bipolar II-diagnosed by the Structured Clinical Interview for DSM-IV (Clinician
      Version), 181 who had clinically recovered from depression were administered the
      Mood Disorder Questionnaire (MDQ of. Am. J. Psychiatry 157, 1873). The MDQ is a
      newly developed, psychometrically validated self-report screening instrument for
      bipolar spectrum disorders. It screens for lifetime history of manic/hypomanic
      symptoms by including yes/no items covering all DSM-IV symptoms of
      mania/hypomania. The MDQ symptom interrelationships were studied by principal
      component analysis with varimax rotation. RESULTS: Hypomanic symptoms occurring
      in >50% were racing thoughts, increased energy and social activity, and
      irritability. Factor analysis revealed two factors: 'Energized-Activity'
      (eigenvalue=3.1) and 'Irritability-Racing Thoughts' (eigenvalue=1.5).
      LIMITATIONS: Cross-sectional assessment. CONCLUSIONS: Self-assessment of past
      hypomanic symptoms by patients, during clinical remission from depression,
      revealed two independent hypomanic factors, neither of which comprised euphoria.
      Hypomanic behavior appears to be more fundamental for the diagnosis of hypomania
      than elated mood accorded priority in DSM-IV; of hypomanic moods, irritability
      had greater significance than elation. It would appear that self-report of
      euphoria is less likely when hypomanias are brief (>or=2 vs. >or=4 days). The
      main implication for busy clinical practice is that energized activity and
      irritable mood associated with racing thoughts represent the modal experiences of
      hypomania among bipolar II outpatients; euphoria is neither sensitive, nor
      pathognomonic, in the diagnosis of these patients. These conclusions accord with
      recommendations made many years ago for the diagnosis of hypomania among
      cyclothymic patients [. Am. J. Psychiatry 134, 1227].

PMID- 12507739
TI  - Validating antidepressant-associated hypomania (bipolar III): a systematic
      comparison with spontaneous hypomania (bipolar II).
AB  - BACKGROUND: According to DSM-IV and ICD-10, hypomania which occurs solely during
      antidepressant treatment does not belong to the category of bipolar II (BP-II).
      METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive
      DSM-IV major depressive patients evaluated in at least two semi-structured
      interviews 1 month apart, 144 (29.2%) fulfilled the criteria for bipolar II with
      spontaneous hypomania (BP-II Sp), and 52 (10.5%) had hypomania associated solely
      with antidepressants (BP-H AA). RESULTS: BP-II Sp group had earlier age at onset,
      more hypomanic episodes, and higher ratings on cyclothymic and hyperthymic
      temperaments, and abused alcohol more often. The two groups were
      indistinguishable on the hypomania checklist score (12.2+/-4.0 vs. 11.4+/-4.4,
      respectively, P=0.25) and on rates of familial bipolarity (14.1% vs. 11.8%,
      respectively, P=0.68). But BP-H AA had significantly more family history of
      suicide, had higher ratings on depressive temperament, with greater chronicity of
      depression, were more likely to be admitted to the hospital for suicidal
      depressions, and were more likely to have psychotic features; finally, clinicians
      were more likely to treat them with ECT, lithium and mood stabilizing
      anticonvulsants. LIMITATION: Naturalistic study, where treatment was
      uncontrolled. CONCLUSION: BP-H AA emerges as a disorder with depressive
      temperamental instability, manifesting hypomania later in life (and, by
      definition, during pharmacotherapy only). By the standards of clinicians who have
      taken care of these patients for long periods of time, BP-H AA appears as no less
      bipolar than those with prototypical BP-II. We submit that familial bipolarity
      ('genotypic' bipolarity) strongly favors their inclusion within the realm of
      bipolar II spectrum, as a prognostically less favorable depression-prone
      phenotype of this disorder, and which is susceptible to destabilization under
      antidepressant treatment. These considerations argue for revisions of DSM-IV and
      ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression
      of BP-II; phenotypically; it might provisionally be categorized as bipolar III.

PMID- 12507740
TI  - Duration and stability of the rapid-cycling course: a long-term personal follow
      up of 109 patients.
AB  - BACKGROUND: Recognition by the DSM-IV of rapid cyclicity as a course specifier
      has raised the question of the stability and long-term outcome of rapid-cycling
      (RC) patients. Data on this topic is sparse and often inconsistent. To our
      knowledge, these are the first personally followed patients over the long term,
      dealing directly with the issue of the duration of the RC course. METHODS: We
      examined the evolution of the course of 109 RC patients (68 women and 41 men)
      followed for a minimum of 2 years and up to 36 years, beginning with the index
      episode when the RC course was diagnosed by the authors (A.K., G.P.M., P.G.,
      L.P., D.R.). Patients were included in the study if they met criteria for RC as
      defined by>or=4 affective episodes per year (Dunner and Fieve, 1974). The follow
      up period varied from 2-5 years for 25 patients, 6-10 years for 24 patients, 11
      15 years for 24 patients, 16-20 years for 19 patients, 21-25 years for 13
      patients, 30-36 years for four patients. RESULTS: In 13 patients (12%), RC
      emerged spontaneously and in 96 patients (88%), it was associated with
      antidepressant and other treatments. In 19 women (28% of all women) RC course
      started in perimenopausal age (45-54 years). The mean duration of RC during the
      follow-up period was 7.86 years (range 1-32) and its total duration (including RC
      course prior to the follow-up period) was 11 years (range 1-40). The total
      duration of the affective disorder, from the first episode to the end of the
      follow-up, was 21.78 years (range 1-70). At the end of the follow-up, 36 patients
      (33%) had complete remission for at least the past year, 44 (40%) stayed rapid
      cycling with severe episodes (six of this group committed suicide), while 15
      (14%) were rapid cycling but with attenuated episodes. The other 14 patients
      (13%) became long cyclers, eight with severe episodes and six with milder ones.
      The main distinguishing features between those who remitted from and those who
      persisted in the RC course were: (1). the initial cycle pattern: patients with
      Depression-Hypomania(mania)-Free interval cycles (53 patients) had a worse
      outcome: 26.4% remitted and 52.8% persisted in the RC course through to the end
      of the follow up period. The Mania/Hypomania-Depression-Free interval cycles (22
      patients) had a significantly better outcome, with 50% remitted and 27.2%
      persisting RC; and (2). the occurrence of the switch process from depression to
      hypomania/mania and the occurrence of agitated depressions made the prognosis
      worse. Continuous treatment was more effective against mania/hypomania than
      against depression, yet in all persisting RC cases the mania/hypomania remitted
      only partially. LIMITATIONS: These data derive from clinics known for their
      expertise in mood disorders, and they may have attracted and retained patients
      with a more severe course. Treatment was uncontrolled and consisted more of
      lithium than divalproex, lamotrigene and olanzapine, recently shown to be
      beneficial in subgroups of patients with rapid-cycling. CONCLUSIONS: Our findings
      suggest that rapid cyclicity, spontaneous or induced, once established, becomes
      for many years a stable rhythm in a substantial proportion of patients, linked to
      endogenous and environmental factors. The suggestion is made to consider as rapid
      cyclers, at least for research purposes, those patients who have had a rapid
      cycling course for at least 2 years, borrowing the duration criterion currently
      employed for other chronic disorders such as Dysthymia and Cyclothymia. That our
      patients had poorer prognosis than some other cohorts in the literature is
      probably due to the shorter duration of "rapid-cycling" at entry in the latter
      cohorts. A true understanding of the nature of rapid-cycling will require a
      rigorous definition of not only duration, but also pole-switching and course
      patterns at entry into study.

PMID- 12507741
TI  - The role of cyclothymia in atypical depression: toward a data-based
      reconceptualization of the borderline-bipolar II connection.
AB  - OBJECTIVE: Recent data, including our own, indicate significant overlap between
      atypical depression and bipolar II. Furthermore, the affective fluctuations of
      patients with these disorders are difficult to separate, on clinical grounds,
      from cyclothymic temperamental and borderline personality disorders. The present
      analyses are part of an ongoing Pisa-San Diego investigation to examine whether
      interpersonal sensitivity, mood reactivity and cyclothymic mood swings constitute
      a common diathesis underlying the atypical depression-bipolar II-borderline
      personality constructs. METHOD: We examined in a semi-structured format 107
      consecutive patients who met criteria for major depressive episode with DSM-IV
      atypical features. Patients were further evaluated on the basis of the Atypical
      Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL-90),
      and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified
      form for reverse vegetative features as well as Axis I and SCID-II evaluated Axis
      II comorbidity, and cyclothymic dispositions ('APA Review', American Psychiatric
      Press, Washington DC, 1992). RESULTS: Seventy-eight percent of atypical
      depressives met criteria for bipolar spectrum-principally bipolar II-disorder.
      Forty-five patients who met the criteria for cyclothymic temperament, compared
      with the 62 who did not, were indistinguishable on demographic, familial and
      clinical features, but were significantly higher in lifetime comorbidity for
      panic disorder with agoraphobia, alcohol abuse, bulimia nervosa, as well as
      borderline and dependent personality disorders. Cyclothymic atypical depressives
      also scored higher on the ADDS items of maximum reactivity of mood, interpersonal
      sensitivity, functional impairment, avoidance of relationships, other rejection
      avoidance, and on the interpersonal sensitivity, phobic anxiety, paranoid
      ideation and psychoticism of the HSCL-90 factors. The total number of cyclothymic
      traits was significantly correlated with 'maximum' reactivity of mood and
      interpersonal sensitivity. A significant correlation was also found between
      interpersonal sensitivity and 'usual' and 'maximum' reactivity of mood.
      LIMITATION: Correlational study. CONCLUSIONS: Mood lability and interpersonal
      sensitivity traits appear to be related by a cyclothymic temperamental diathesis
      which, in turn, appears to underlie the complex pattern of anxiety, mood and
      impulsive disorders which atypical depressive, bipolar II and borderline patients
      display clinically. We submit that conceptualizing these constructs as being
      related will make patients in this realm more accessible to pharmacological and
      psychological interventions geared to their common temperamental attributes. More
      generally, we submit that the construct of borderline personality disorder is
      better covered by more conventional diagnostic entities.

PMID- 12507742
TI  - TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological
      considerations on the relevance of joint anxious-depressive temperament traits.
AB  - BACKGROUND: Temperament is an important factor in affective illness. There is
      some indication that mixed episodes result from an admixture of inverse
      temperamental factors (e.g. depressive and/or anxious) to a manic syndrome. To
      test this hypothesis, which has been first formulated by Akiskal [Clin.
      Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared the temperament of
      non-acute bipolar affective patients with and without the history of a previous
      mixed episode. METHODS: Patients who had been hospitalized for a bipolar disorder
      were re-assessed at least 6 months after their last in-patient treatment. Those
      who met the criteria for a partially remitted or full affective or psychotic
      episode at re-assessment were excluded from the study. Data concerning illness
      history, current psychopathology (SCID-I interview), depression (BDI), mania
      (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained.
      Patients with and without a history of previous mixed episodes were compared.
      RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without
      a former mixed episode in bipolar affective disorder fulfilled the inclusion
      criteria. Subjects suffering from bipolar affective disorder exhibited
      significantly more depressive and anxious and less hyperthymic temperament, if
      they had experienced a mixed episode previously. Concerning cyclothymic and
      irritable temperament, bipolar affective patients with a former mixed episode
      presented non-significantly higher scores. Patients with a former mixed episode
      presented with higher depression scores than patients without such a history. No
      group differences were found concerning current mania scores. LIMITATIONS: (1).
      This is a preliminary report from an ongoing study. (2). Temperament had not been
      assessed premorbidly. (3). Although group comparisons revealed significant
      differences, these did not seem great enough to fully explain the emergence of a
      mixed episode. CONCLUSION: Our findings support the study's hypothesis that mixed
      episodes occur more often in subjects with an inverse temperament (e.g.
      depressive and anxious), although it cannot be ruled out that subsyndromal
      features of the bipolar illness had an effect on temperament assessment.

PMID- 12507743
TI  - Impulsivity and phase of illness in bipolar disorder.
AB  - BACKGROUND: Impulsivity is prominent in bipolar disorder, but there is little
      quantitative information relating it to phase of illness. METHODS: We measured
      impulsivity in patients with bipolar disorder who had not met episode criteria
      for at least 6 months, patients who were manic, and healthy control subjects.
      Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and
      performance on the computerized Immediate Memory-Remote Memory Task (IMT-DMT),
      based on the Continuous Performance Test, which has been shown to reflect risk of
      impulsivity in other populations. RESULTS: BIS scores in euthymic and manic
      bipolar subjects were identical, and were significantly elevated compared to
      controls. Commission errors (impulsive responses) on the IMT-DMT were elevated in
      manic subjects but were identical to controls in euthymic subjects. Measures of
      impulsivity did not appear related to depressive symptoms. LIMITATIONS: The
      number of subjects was too small for detailed investigation of the role of
      comorbidities; subjects were receiving pharmacological treatments. CONCLUSIONS:
      Impulsivity has state- and trait-related aspects in bipolar disorder.

PMID- 12507744
TI  - Family history validation of the bipolar nature of depressive mixed states.
AB  - BACKGROUND: Recent data indicate that depressive mixed states (DMX), major
      depressive episode (MDE) plus few concurrent hypomanic symptoms are common in
      clinical practice but omitted in DSM-IV. Our aims were to find the sensitivity
      and specificity of DMX for the diagnosis of bipolar II disorder, and validate it
      against familial bipolarity. METHODS: 377 consecutive private outpatients
      presenting with psychoactive drug-free MDE were interviewed with the Structured
      Clinical Interview for DSM-IV (Clinician Version). History of past hypomanic
      episodes and presence of hypomanic symptoms during the index MDE were
      systematically recorded. Of these, 226 were bipolar II and 151 unipolar. DMX3 was
      defined as an MDE plus three or more intra-episodic hypomanic symptoms. RESULTS:
      DMX3 was present in 58.4% of bipolar II, and 23.1% of unipolar patients. It was
      significantly associated with variables distinguishing bipolar from strictly
      defined unipolar disorders (younger age at onset, more MDE recurrence, more
      atypical features, more bipolar II family history). Unipolar DMX3 (MDE with
      documented hypomania solely intra-episodically) was not significantly different
      from bipolar II MDE on age at onset, atypical features, and bipolar II family
      history. CONCLUSIONS: Results support the inclusion of DMX3 (bipolar II and
      'unipolar') into the bipolar spectrum. Adding the 23% of the UP-DMX3 to the
      roster of less-than-manic outpatient depressives will boost the rate of
      bipolarity in this outpatient depressive population to a respectable 70%, the
      highest rate yet reported for the bipolar spectrum below the threshold of mania.

PMID- 12507745
TI  - The prevalence and disability of bipolar spectrum disorders in the US population:
      re-analysis of the ECA database taking into account subthreshold cases.
AB  - BACKGROUND: Despite emerging international consensus on the high prevalence of
      the bipolar spectrum in both clinical and community samples, many skeptics
      contend that narrowly defined bipolar disorder with a lifetime rate of about 1%
      represents a more accurate estimate of prevalence. This may in part be due to the
      fact that higher figures proposed for the bipolar spectrum (5-8%) have not been
      based on national data and have not included all levels of manic symptom
      severity. In the present secondary analyses of the US National Epidemiological
      Catchment Area (ECA) database, we provide further clarification on this
      fundamental public health issue. METHODS: All respondents in the first wave
      (first interview) of the ECA household five site sample (n=18252) were classified
      on the basis of DSM-III criteria into lifetime manic and hypomanic episodes, as
      well as those with at least two lifetime manic/hypomanic symptoms below the
      threshold for at least 1 week duration (subsyndromal manic symptoms [SSM] group).
      Odds ratios were calculated on lifetime service utilization for mental health
      problems, measures of adverse psychosocial outcome, and suicidal behavior
      compared to subjects with no mental disorders or manic symptoms. RESULTS: As
      originally reported nearly two decades ago by the primary investigators of the
      ECA, the lifetime prevalence for manic episode was 0.8%, and for hypomania, 0.5%.
      What is new here is the inclusion of subthreshold SSM subjects, which accounted
      for 5.1%, yielding a total of 6.4% lifetime prevalence for the bipolar spectrum.
      All three (manic, hypomanic and SSM) groups had greater marital disruption. There
      were significant increases in lifetime health service utilization, need for
      welfare and disability benefits and suicidal behavior when the SSM, hypomanic and
      manic subjects were compared to the no mental disorder group. Suicidal behavior
      was non-significantly highest in the hypomanic (bipolar II) group. Otherwise,
      hypomanic and manic groups had comparable level of service utilization and social
      disruption. LIMITATIONS: Comorbid disorders, which might influence functioning,
      were not included in the present analyses. CONCLUSION: These secondary analyses
      of the US National ECA database provide convincing evidence for the high
      prevalence of a spectrum of bipolarity in the community at 6.4%, and indicate
      that subthreshold cases are at least five times more prevalent than DSM-based
      core syndromal diagnoses at about 1%. These SSM subjects, who met the criteria of
      "caseness" from the point of view of harmful dysfunction, are of great
      theoretical and public health significance.

PMID- 12507746
TI  - Toward a re-definition of subthreshold bipolarity: epidemiology and proposed
      criteria for bipolar-II, minor bipolar disorders and hypomania.
AB  - BACKGROUND: The boundaries of bipolarity have been expanding over the past
      decade. Using a well characterized epidemiologic cohort, in this paper our
      objectives were: (1). to test the diagnostic criteria of DSM-IV hypomania, (2).
      to develop and validate criteria for the definition of softer expressions of
      bipolar-II (BP-II) disorder and hypomania, (3). to demonstrate the prevalence,
      clinical validity and comorbidity of the entire soft bipolar spectrum. METHODS:
      Data on the continuum from normal to pathological mood and overactivity,
      collected from a 20-year prospective community cohort study of young adults, were
      used. Clinical validity was analysed by family history, course and clinical
      characteristics, including the association with depression and substance abuse.
      RESULTS: (1). Just as euphoria and irritability, symptoms of overactivity should
      be included in the stem criterion of hypomania; episode length should probably
      not be a criterion for defining hypomania as long as three of seven signs and
      symptoms are present, and a change in functioning should remain obligatory for a
      rigorous diagnosis. (2). Below that threshold, 'hypomanic symptoms only'
      associated with major or mild depression are important indicators of bipolarity.
      (3). A broad definition of bipolar-II disorder gives a cumulative prevalence rate
      of 10.9%, compared to 11.4% for broadly defined major depression. A special group
      of minor bipolar disorder (prevalence 9.4%) was identified, of whom 2.0% were
      cyclothymic; pure hypomania occurred in 3.3%. The total prevalence of the soft
      bipolar spectrum was 23.7%, comparable to that (24.6%) for the entire depressive
      spectrum (including dysthymia, minor and recurrent brief depression). LIMITATION:
      A national cohort with a larger number of subjects is needed to verify the
      numerical composition of the softest bipolar subgroups proposed herein.
      CONCLUSION: The diagnostic criteria of hypomania need revision. On the basis of
      its demonstrated clinical validity, a broader concept of soft bipolarity is
      proposed, of which nearly 11% constitutes the spectrum of bipolar disorders
      proper, and another 13% probably represent the softest expression of bipolarity
      intermediate between bipolar disorder and normality.

PMID- 12507747
TI  - Placebo-controlled trials do not find association of olanzapine with exacerbation
      of bipolar mania.
AB  - BACKGROUND: Published case reports describe apparent induction or exacerbation of
      manic-like symptoms during treatment with the atypical antipsychotics olanzapine
      and risperidone. To date, such reports are from uncontrolled clinical experience
      and therefore cannot clarify whether the atypical antipsychotics caused such
      manic-like states or simply failed to prevent them. Presumably, bipolar patients
      would be at increased risk for this putative adverse event. Therefore, we
      evaluated the potential of olanzapine to exacerbate symptoms of mania compared to
      placebo during treatment of bipolar mania. METHODS: Two inpatient, double-blind,
      randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus
      placebo for the treatment of acute mania were combined. Two hundred and fifty
      four subjects participated (placebo n=129; olanzapine n=125) in the two studies.
      Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y
      MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks,
      categorical comparison of olanzapine and placebo groups was made for any
      worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF). RESULTS:
      The percentage of subjects with exacerbation at endpoint were: any worsening,
      placebo 37.7%, olanzapine 21.8% (P=0.005); >or=10% worsening, placebo 24.6%,
      olanzapine 14.5% (P=0.039); >or=20% worsening, placebo 15.6%, olanzapine 8.1%
      (P=0.064). CONCLUSION: Mania rating scores worsened for some patients during
      olanzapine therapy. However, this was significantly less common with olanzapine
      than with placebo. These controlled data suggest that clinical case reports of
      occurrence of 'mania' during treatment with olanzapine, and possibly those with
      other atypical antipsychotics, reflect exacerbation in the natural history of
      bipolar illness, rather than an adverse pharmacological effect. LIMITATIONS: Post
      hoc analysis of pooled data from two different studies.

PMID- 12507748
TI  - Olanzapine in the acute treatment of bipolar I disorder with a history of rapid
      cycling.
AB  - BACKGROUND: A substantial proportion of patients with bipolar disorder are
      characterized by a rapidly cycling course and are particularly resistant to
      conventional treatment. METHODS: This secondary analysis, defined a priori, was
      conducted on a larger data set from patients with bipolar I disorder to determine
      the efficacy of a 3-week treatment with the atypical antipsychotic olanzapine (5
      20 mg/day, n=19) versus placebo (n=26) in patients with >or=4 episodes in the
      preceding year. RESULTS: Significantly fewer placebo patients completed treatment
      (34.6 vs. 73.7%, P=0.016), and more than half discontinued due to lack of
      efficacy (53.8 vs. 21.1%, P=0.035). Olanzapine reduced Young Mania Rating Scale
      (YMRS) total scores significantly more than placebo (-13.9 vs. -4.1, P=0.011).
      Clinical responses, defined as >or=50% improvement in YMRS, were achieved in 58%
      of olanzapine patients, compared with 28% of placebo patients (P=0.066).
      Extrapyramidal symptoms were not significantly changed in either group.
      Somnolence was the most common adverse event in both groups (olanzapine: 52.6%,
      placebo: 23.1%; P=0.060). No event occurred significantly more frequently with
      olanzapine than with placebo. No patients discontinued due to an adverse event.
      LIMITATIONS: The duration of this study was limited to 3 weeks, precluding
      conclusions about long-term efficacy of olanzapine. Moreover, a sizeable placebo
      effect was obtained, possibly masking optimal therapeutic effect. Despite these
      limitations, treatment differences in efficacy were highly significant.
      CONCLUSIONS: These results indicate that olanzapine was effective in reducing
      symptoms of mania and well tolerated in patients with bipolar I disorder with a
      rapid-cycling course.

PMID- 12507749
TI  - Redefining mood stabilization.
AB  - This review considers the definition of the term 'mood-stabilizer' in the context
      of new pharmacological agents for the treatment of bipolar disorder. Three
      definitions of a mood-stabilizer are described and the available data from
      randomized, double-blind, controlled trials for putative mood-stabilizers studied
      in the treatment of different aspects of bipolar disorder (mania, mixed states,
      depression, maintenance) are reviewed. No available agent meets the criteria for
      a comprehensive mood-stabilizer, although lithium comes the closest.

PMID- 12507750
TI  - Psychoeducational and cognitive-behavioral strategies in the management of
      bipolar disorder.
AB  - Despite advances in the pharmacologic treatment of bipolar disorder, it is clear
      that additional strategies are needed to provide patients with longer-term mood
      stability. Recent years have witnessed the development of a number of
      psychosocial strategies for bipolar disorder that are design as adjuncts to
      ongoing pharmacotherapy. In this article we describe psychoeducational and
      cognitive-behavioral approaches to the management of bipolar disorder, with
      emphasis on broader treatment packages that can be offered by cognitive-behavior
      therapists working in specialty bipolar clinics, as well as specific strategies
      that can be integrated into standard pharmacotherapy for the disorder. A growing
      body of evidence documents the potential value of these interventions, and large
      scale studies are underway, including the Systematic Treatment Enhancement
      Program for Bipolar Disorder (STEP-BD), which will provide outcome on these
      interventions from the perspective of large, multicenter trials.

PMID- 12507751
TI  - Arguments for the genetic basis of the bipolar spectrum.
AB  - Family members of bipolar probands have been repeatedly shown to have an
      increased risk for mood disorders. However, a range of different syndromes in the
      bipolar spectrum are commonly observed in these relatives. This suggests the
      hypothesis that these different syndromes may be genetically related. It further
      suggests that bipolar disorder may be better conceptualized from a genetic
      standpoint as a quantitative trait. In such a model, the same genes may
      predispose to a variety of phenotypes ranging from schizoaffective disorder to
      cyclothymic temperament. Previous attempts to test such a multifactorial model
      have provided some limited support. However, other studies argue that some forms
      of bipolar disorder such as bipolar II may be genetically distinct. In this
      review, various quantitative and categorical models of illness are considered and
      the data supporting them reviewed. It is proposed that the existing data may best
      fit a model in which different sets of genes predispose to overlapping phenotypes
      that are in part both quantitative and distinct in nature.

PMID- 12507752
TI  - Ewald Hecker's description of cyclothymia as a cyclical mood disorder: its
      relevance to the modern concept of bipolar II.

PMID- 12507753
TI  - The superfamily of organic anion transporting polypeptides.
AB  - Organic anion transporting polypeptides (Oatps/OATPs) form a growing gene
      superfamily and mediate transport of a wide spectrum of amphipathic organic
      solutes. Different Oatps/OATPs have partially overlapping and partially distinct
      substrate preferences for organic solutes such as bile salts, steroid conjugates,
      thyroid hormones, anionic oligopeptides, drugs, toxins and other xenobiotics.
      While some Oatps/OATPs are preferentially or even selectively expressed in one
      tissue such as the liver, others are expressed in multiple organs including the
      blood-brain barrier (BBB), choroid plexus, lung, heart, intestine, kidney,
      placenta and testis. This review summarizes the actual state of the rapidly
      expanding OATP superfamily and covers the structural properties, the genomic
      classification, the phylogenetic relationships and the functional transport
      characteristics. In addition, we propose a new species independent and open ended
      nomenclature and classification system, which is based on divergent evolution and
      agrees with the guidelines of the Human Genome Nomenclature Committee.

PMID- 12507754
TI  - Beta-barrel membrane protein folding and structure viewed through the lens of
      alpha-hemolysin.
AB  - The beta-barrel is a transmembrane structural motif commonly encountered in
      bacterial outer membrane proteins and pore-forming toxins (PFTs). Alpha-hemolysin
      (alphaHL) is a cytotoxin secreted by Staphylococcus aureus that assembles from a
      water-soluble monomer to form a membrane-bound heptameric beta-barrel on the
      surface of susceptible cells, perforating the cell membranes, leading to cell
      death and lysis. The mechanism of heptamer assembly, which has been studied
      extensively, occurs in a stepwise manner, and the structures of the initial,
      monomeric form and final, membrane-embedded pore are known. The toxin's ability
      to assemble from an aqueous, hydrophilic species to a membrane-inserted oligomer
      is of interest in understanding the assembly of PFTs in particular and the
      folding and structure of beta-barrel membrane proteins in general. Here we review
      the structures of the monomeric and heptamer states of LukF and alphaHL,
      respectively, the mechanism of toxin assembly, and the relationships between
      alphaHL and nontoxin beta-barrel membrane proteins.

PMID- 12507755
TI  - Piracetam inhibits the lipid-destabilising effect of the amyloid peptide Abeta C
      terminal fragment.
AB  - Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor
      protein (APP), implicated in the pathogenesis of Alzheimer's disease. The
      hypothesis that interactions between Abeta aggregates and neuronal membranes play
      an important role in toxicity has gained some acceptance. Previously, we showed
      that the C-terminal domain (e.g. amino acids 29-42) of Abeta induces membrane
      permeabilisation and fusion, an effect which is related to the appearance of non
      bilayer structures. Conformational studies showed that this peptide has
      properties similar to those of the fusion peptide of viral proteins i.e. a tilted
      penetration into membranes. Since piracetam interacts with lipids and has
      beneficial effects on several symptoms of Alzheimer's disease, we investigated in
      model membranes the ability of piracetam to hinder the destabilising effect of
      the Abeta 29-42 peptide. Using fluorescence studies and 31P and 2H NMR
      spectroscopy, we have shown that piracetam was able to significantly decrease the
      fusogenic and destabilising effect of Abeta 29-42, in a concentration-dependent
      manner. While the peptide induced lipid disorganisation and subsequent negative
      curvature at the membrane-water interface, the conformational analysis showed
      that piracetam, when preincubated with lipids, coats the phospholipid headgroups.
      Calculations suggest that this prevents appearance of the peptide-induced
      curvature. In addition, insertion of molecules with an inverted cone shape, like
      piracetam, into the outer membrane leaflet should make the formation of such
      structures energetically less favourable and therefore decrease the likelihood of
      membrane fusion.

PMID- 12507756
TI  - Uptake of dipeptide and beta-lactam antibiotics by the basolateral membrane
      vesicles prepared from rat kidney.
AB  - The transport of dipeptides and beta-lactam antibiotics across the rat renal
      basolateral membrane was examined. The initial uptake of glycylsarcosine and
      cefadroxil by rat renal basolateral membrane vesicles was inhibited by the
      presence of all the di- and tripeptides and beta-lactam antibiotics that were
      tested in this study. However, the uptake of both substrates was not inhibited by
      glycine, an amino acid. The initial uptake of zwitterionic beta-lactam
      antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded
      glycylsarcosine (countertransport effect). On the other hand, the uptake of
      dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected. A
      concentration-dependent initial uptake of glycylsarcosine and cefadroxil
      suggested the existence of a carrier-mediated mechanism, whereas the transport of
      ceftibuten did not show any saturated uptake. The transporter that participates
      in the permeation of dipeptides and beta-lactam antibiotics across basolateral
      membranes showed lower affinity than did PEPT1 and PEPT2. This is the first study
      that showed an evidence for a peptide transporter, expressed in the rat renal
      basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using
      basolateral membrane vesicles isolated from normal rat kidney.

PMID- 12507757
TI  - Membrane structure of the human immunodeficiency virus gp41 fusion peptide by
      molecular dynamics simulation. II. The glycine mutants.
AB  - In this work, molecular dynamics (MD) simulation of the interaction of three
      mutants, G3V, G5V and G10V, of the human immunodeficiency virus (HIV) gp41 16
      residue fusion peptide (FP) with an explicit palmitoyloleoylphosphatidyl
      ethanolamine (POPE) lipid bilayer was performed. The goals of this work are to
      study the correlation of the fusogenic activity of the FPs with the mode of their
      interaction with the bilayer and to examine the roles of the many glycine
      residues in the FP in the fusion process. The results of this work corroborate
      the main conclusion of our earlier MD work of the WT FP and several mutants with
      polar substitution. These two studies provide correlation between the mode of
      insertion and the fusogenic activity of these peptides and support the hypothesis
      that an oblique insertion of the fusion domain of the viral protein is required
      for fusogenic activity. Inactive mutants interact with the bilayer by a surface
      binding mode. The results of this work, combined with the results of our earlier
      work, show that, while the secondary structures of the wild-type FP and its
      mutants do not affect the fusogenic activities, the conformational flexibility
      appears to be an important factor. The active WT FP and its partially active
      mutants, G3V and G5V, all have significant conformational transitions at one of
      the glycine sites. They occur at Gly(5) in FP-wt, at Gly(10) in FP-G5V and at
      Gly(13) in FP-G3V. Thus, a glycine site in each of these active (or partially
      active) FPs provides conformational flexibility. On the other hand, the inactive
      mutants FP-G10V, FP-L9R and FP-V2E do not have any conformational transitions
      except at either terminus and thus possess no conformational flexibility. Thus,
      the results of this work support the suggestion that the role of glycine residues
      in the fusion domain is to provide the necessary conformational flexibility for
      fusion activity. The glycines also form a "glycine strip" in the FP that locates
      on one (the less hydrophobic) face of the helix (the "sided helix"). However,
      whether this "glycine strip" is disrupted or not does not seem to correlate with
      the retention of fusogenic activities. Finally, although the FLGFL (8-12) motif
      is absolutely conserved in the HIV fusion domain, a well-structured motif
      stabilized by hydrogen bonding does not appear to be required for activity. In
      fact, hydrogen bonding in this motif was found to be missing in FP-G3V and FP
      G5V. Both of these mutants are partially active.

PMID- 12507758
TI  - Functional role of the N-terminus of Na(+),K(+)-ATPase alpha-subunit as an
      inactivation gate of palytoxin-induced pump channel.
AB  - The N-terminus of the Na(+),K(+)-ATPase alpha-subunit shows some homology to that
      of Shaker-B K(+) channels; the latter has been shown to mediate the N-type
      channel inactivation in a ball-and-chain mechanism. When the Torpedo Na(+),K(+)
      ATPase is expressed in Xenopus oocytes and the pump is transformed into an ion
      channel with palytoxin (PTX), the channel exhibits a time-dependent inactivation
      gating at positive potentials. The inactivation gating is eliminated when the N
      terminus is truncated by deleting the first 35 amino acids after the initial
      methionine. The inactivation gating is restored when a synthetic N-terminal
      peptide is applied to the truncated pumps at the intracellular surface. Truncated
      pumps generate no electrogenic current and exhibit an altered stoichiometry for
      active transport. Thus, the N-terminus of the alpha-subunit appears to act like
      an inactivation gate and performs a critical step in the Na(+),K(+)-ATPase
      pumping function.

PMID- 12507759
TI  - The influence of repeated injections on pharmacokinetics and biodistribution of
      different types of sterically stabilized immunoliposomes.
AB  - Sterically stabilized immunoliposomes (IL) with diameters of about 135 nm
      carrying mouse IgG, either coupled directly to the liposome surface, or linked to
      the terminal ends of grafted poly(ethylene glycol) (PEG) chains by a recently
      described conjugation procedure (Cyanur-PEG-PE), were intravenously injected into
      rats and the elimination kinetics and biodistribution were determined and
      compared with control liposomes. The amounts of conjugated antibodies were about
      30 microg/micromol total lipid for all IL. In naive rats, plain pegylated
      liposomes displayed the longest blood circulation time, whereas the terminal
      coupled IL exhibited the fastest elimination. Liposomes containing the
      underivatized anchor molecules circulate nearly as long as plain pegylated
      liposomes, indicating that the fast elimination of the IL can be attributed to
      the presence of antibodies.A second injection of identical liposomes 14 days
      after the first injection had a considerable influence on the pharmacokinetic
      parameters of the liposomes. The circulation time of plain pegylated liposomes
      drastically dropped by half and their uptake by the liver increased
      concomitantly, indicating that the PEG, upon repeated injection, ceases to
      function as an efficient barrier reducing opsonization and/or immune reactions.
      The circulation time of conventional IL was moderately reduced upon a second
      injection, whereas that of the terminally coupled IL was nearly unaffected. These
      differences among the IL demonstrate that the pharmacokinetic behavior of IL is
      strongly dependent on the antibody conjugation site on the liposome. The observed
      effects of repeated injections were similar for liposomes of 90-nm diameter. The
      phenomena described may have important implications for the repeated application
      of IL as drug carriers.

PMID- 12507760
TI  - Ratiometric fluorescence measurements of membrane potential generated by yeast
      plasma membrane H(+)-ATPase reconstituted into vesicles.
AB  - Potential-sensitive fluorescent probes oxonol V and oxonol VI were employed for
      monitoring membrane potential (Delta(psi)) generated by the Schizosaccharomyces
      pombe plasma membrane H(+)-ATPase reconstituted into vesicles. Oxonol VI was used
      for quantitative measurements of the Delta(psi) because its response to membrane
      potential changes can be easily calibrated, which is not possible with oxonol V.
      However, oxonol V has a superior sensitivity to Delta(psi) at very low
      concentration of reconstituted vesicles, and thus it is useful for testing
      quality of the reconstitution. Oxonol VI was found to be a good emission
      ratiometric probe. We have shown that the reconstituted H(+)-ATPase generates
      Delta(psi) of about 160 mV on the vesicle membrane. The generated Delta(psi) was
      stable at least over tens of minutes. An influence of the H(+) membrane
      permeability on the Delta(psi) buildup was demonstrated by manipulating the H(+)
      permeability with the protonophore CCCP. Ratiometric measurements with oxonol VI
      thus offer a promising tool for studying processes accompanying the yeast plasma
      membrane H(+)-ATPase-mediated Delta(psi) buildup.

PMID- 12507761
TI  - Expression of aquaporin 1 and aquaporin 4 water channels in rat choroid plexus.
AB  - The role of aquaporins in cerebrospinal fluid (CSF) secretion was investigated in
      this study. Western analysis and immunocytochemistry were used to examine the
      expression of aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in the rat choroid plexus
      epithelium. Western analyses were performed on a membrane fraction that was
      enriched in Na(+)/K(+)-ATPase and AE2, marker proteins for the apical and
      basolateral membranes of the choroid plexus epithelium, respectively. The AQP1
      antibody detected peptides with molecular masses of 27 and 32 kDa in fourth and
      lateral ventricle choroid plexus. A single peptide of 29 kDa was identified by
      the AQP4 antibody in fourth and lateral ventricle choroid plexus.
      Immunocytochemistry demonstrated that AQP1 is expressed in the apical membrane of
      both lateral and fourth ventricle choroid plexus epithelial cells. The
      immunofluorescence signal with the AQP4 antibody was diffusely distributed
      throughout the cytoplasm, and there was no evidence for AQP4 expression in either
      the apical or basolateral membrane of the epithelial cells. The data suggest that
      AQP1 contributes to water transport across the apical membrane of the choroid
      plexus epithelium during CSF secretion. The route by which water crosses the
      basolateral membrane, however, remains to be determined.

PMID- 12507762
TI  - Regulation of basolateral organic anion transporters in ethinylestradiol-induced
      cholestasis in the rat.
AB  - BACKGROUND/AIMS: Estrogen-mediated cholestasis is an important clinical entity,
      but its molecular pathophysiology is still not fully understood. Impaired sodium
      dependent uptake of bile acids has been associated with diminished expression of
      a basolateral Na(+)/bile acid cotransporter (Ntcp), whereas sodium-independent
      uptake is maintained despite a down-regulation of the organic anion transporter
      Oatp1. Thus, expression of the two other rat Oatps (Oatps2 and -4) was determined
      in estrogen-induced cholestasis. In addition, known transactivators of Oatp2 and
      Ntcp were studied to further characterize transcriptional regulation of these
      transporter genes. METHODS: Hepatic protein and mRNA expression of various Oatps
      (1, 2, 4) in comparison to Ntcp were analyzed after 0.5, 1, 3 and 5 days of
      ethinylestradiol (EE) treatment (5 mg/kg) in rats. Binding activities of Oatp2
      and Ntcp transactivators were assessed by electrophoretic mobility shift assays.
      RESULTS: All basolateral Oatps (1, 2 and 4) were specifically down-regulated at
      the protein level by 30-40% of controls, but less pronounced than Ntcp (minus 70
      80%). In contrast to unaltered Oatp4 mRNA levels, Oatp1 and Oatp2 mRNAs were
      reduced to various extents (minus 40-90% of controls). Binding activity of known
      transactivators of Ntcp and Oatp2 such as hepatocyte nuclear factor 1 (HNF1),
      CAAT enhancer binding protein alpha (C/EBPalpha) and pregnane X receptor (PXR)
      were also diminished during the time of cholestasis. CONCLUSIONS: Estrogen
      induced cholestasis results in a down-regulation of all basolateral organic anion
      transporters. The moderate decline in expression of Oatp1, -2 and -4 may explain
      the unchanged sodium-independent transport of bile acids due to overlapping
      substrate specificity. Reduction in transporter gene expression seems to be
      mediated by a diminished nuclear binding activity of transactivators such as
      HNF1, C/EBP and PXR by estrogens.

PMID- 12507763
TI  - Secreted phospholipase A(2) as a new enzymatic trigger mechanism for localised
      liposomal drug release and absorption in diseased tissue.
AB  - Polymer-coated liposomes can act as versatile drug-delivery systems due to long
      vascular circulation time and passive targeting by leaky blood vessels in
      diseased tissue. We present an experimental model system illustrating a new
      principle for improved and programmable drug-delivery, which takes advantage of
      an elevated activity of secretory phospholipase A(2) (PLA(2)) at the diseased
      target tissue. The secretory PLA(2) hydrolyses a lipid-based proenhancer in the
      carrier liposome, producing lyso-phospholipids and free fatty acids, which are
      shown in a synergistic way to lead to enhanced liposome destabilization and drug
      release at the same time as the permeability of the target membrane is enhanced.
      Moreover, the proposed system can be made thermosensitive and offers a rational
      way for developing smart liposome-based drug delivery systems. This can be
      achieved by incorporating specific lipid-based proenhancers or prodestabilisers
      into the liposome carrier, which automatically becomes activated by PLA(2) only
      at the diseased target sites, such as inflamed or cancerous tissue.

PMID- 12507764
TI  - Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of
      liposome diameter and implications for toxicity and therapeutic activity.
AB  - The influence of diameter on the pharmacokinetic and biodistribution of STEALTH
      liposomes into the tumor (4T1 murine mammary carcinoma) and cutaneous tissues
      (skin and paws) of mice was studied to ascertain the time course of liposome
      accumulation and to determine if a preferential accumulation of liposomes into
      tumor over skin or paws could be achieved by altering liposome size. These
      tissues were chosen as the dose-limiting toxicity for Caelyx/Doxil in humans is
      palmar-plantar erythrodysesthesia, a cutaneous toxicity. We examined liposomes of
      four diameters: 82, 101, 154, or 241 nm. Liposomes with the three smallest
      diameters showed similar accumulation profiles that were significantly higher
      than the largest liposomes in all three tissues of interest. We were unable to
      achieve a preferential accumulation of liposomes into tumor over skin or paws
      based on size alone, as evidenced by the tumor to skin and tumor to paw ratios.
      However, there were differences in the time courses of liposome accumulation in
      these three tissues. Liposome levels plateaued in tumors and paws within 24 h,
      whereas skin levels plateaued between 24 and 48 h. The therapeutic activity of
      liposomal doxorubicin of three diameters (100, 157, and 255 nm) was tested in the
      same model. All formulations delayed tumor growth, with liposomes of 100 or 157
      nm being equally efficacious and superior to liposomes of 255 nm.

PMID- 12507765
TI  - Redox potentials of the oriented film of the wild-type, the E194Q-, E204Q- and
      D96N-mutated bacteriorhodopsins.
AB  - The redox potentials of the oriented films of the wild-type, the E194Q-, E204Q-
      and D96N-mutated bacteriorhodopsins (bR), prepared by adsorbing purple membrane
      (PM) sheets or its mutant on a Pt electrode, have been examined. The redox
      potentials (V) of the wild-type bR were -470 mV for the 13-cis configuration of
      the retinal Shiff base in bR and -757 mV for the all-trans configuration in
      H(2)O, and -433 mV for the 13-cis configuration and -742 mV for the all-trans
      configuration in D(2)O. The solvent isotope effect (DeltaV=V(D(2)O)-V(H(2)O)),
      which shifts the redox potential to a higher value, originates from the
      cooperative rearrangements of the extensively hydrogen-bonded water molecules
      around the protonated C=N part in the retinal Schiff base. The redox potential of
      bR was much higher for the 13-cis configuration than that for the all-trans
      configuration. The redox potentials for the E194Q mutant in the extracellular
      region were -507 mV for the 13-cis configuration and -788 mV for the all-trans
      configuration; and for the E204Q mutant they were -491 mV for the 13-cis
      configuration and -769 mV for the all-trans configuration. Replacement of the
      Glu(194) or Glu(204) residues by Gln weakened the electron withdrawing
      interaction to the protonated C=N bond in the retinal Schiff base. The E204
      residue is less linked with the hydrogen-bonded network of the proton release
      pathway compared with E194. The redox potentials of the D96N mutant in the
      cytoplasmic region were -471 mV for the 13-cis configuration and -760 mV for the
      all-trans configuration which were virtually the same as those of the wild-type
      bR, indicating that the D to N point mutation of the 96 residue had no influence
      on the interaction between the D96 residue and the C=N part in the Schiff base
      under the light-adapted condition. The results suggest that the redox potential
      of bR is closely correlated to the hydrogen-bonded network spanning from the
      retinal Schiff base to the extracellular surface of bR in the proton transfer
      pathway.

PMID- 12507766
TI  - The general protein secretory pathway: phylogenetic analyses leading to
      evolutionary conclusions.
AB  - We have identified all homologues in the current databases of the ubiquitous
      protein constituents of the general secretory (Sec) pathway. These
      prokaryotic/eukaryotic proteins include (1) SecY/Sec61alpha, (2) SecE/Sec61gamma,
      (3) SecG/Sec61beta, (4) Ffh/SRP54 and (5) FtsY/SRP receptor subunit-alpha.
      Phylogenetic and sequence analyses lead to major conclusions concerning (1) the
      ubiquity of these proteins in living organisms, (2) the topological uniformity of
      some but not other Sec constituents, (3) the orthologous nature of almost all of
      them, (4) a total lack of paralogues in almost all organisms for which complete
      genome sequences are available, (5) the occurrence of two or even three
      paralogues in a few bacteria, plants, and yeast, depending on the Sec
      constituent, and (6) a tremendous degree of sequence divergence in bacteria
      compared with that in archaea or eukaryotes. The phylogenetic analyses lead to
      the conclusion that with a few possible exceptions, the five families of Sec
      constituents analyzed generally underwent sequence divergence in parallel but at
      different characteristic rates. The results provide evolutionary insights as well
      as guides for future functional studies. Because every organism with a fully
      sequenced genome exhibits at least one orthologue of each of these Sec proteins,
      we conclude that all living organisms have relied on the Sec system as their
      primary protein secretory/membrane insertion system. Because most prokaryotes and
      many eukaryotes encode within their genomes only one of each constituent, we also
      conclude that strong evolutionary pressure has minimized gene duplication events
      leading to the establishment of Sec paralogues. Finally, the sequence diversity
      of bacterial proteins as compared with their archaeal and eukaryotic counterparts
      is in agreement with the suggestion that bacteria were the evolutionary
      predecessors of archaea and eukaryotes.

PMID- 12507767
TI  - Relevance of neuropeptide Y for the neuroimmune crosstalk.
AB  - Both cellular and humoral functions of the immune system are modulated by the
      sympathetic nervous system (SNS). This interaction is mainly mediated by the
      release of catecholamines (CA) and their receptor-specific action on immune
      cells. However, neuropeptide Y (NPY), also present in sympathetic nerve
      terminals, is released upon SNS-stimulation. NPY modulates potent immunological
      effects in vitro and in vivo, such as differentiation of T helper cells, monocyte
      mediator release, NK cell activation, and immune cell redistribution. In addition
      to this direct action within the neuroimmune crosstalk, NPY is also able to
      modulate the immunomodulatory effects of other neurotransmitters, thereby acting
      as a neuroimmune co-transmitter. This review will discuss key findings from
      recent studies, provide implications for the clinical situation, and integrate
      the pleiotropic functions of NPY in the context of neuroimmune interactions.

PMID- 12507768
TI  - Toxoplasma gondii inhibits MHC class II expression in neural antigen-presenting
      cells by down-regulating the class II transactivator CIITA.
AB  - Major histocompatibility complex (MHC) class II expression by microglia and
      astrocytes is critical for CD4+-mediated immune responses within the central
      nervous system. Here, we demonstrate that the obligate intracellular parasite,
      Toxoplasma gondii, down-regulates activation-induced MHC class II expression in
      human-derived glioblastoma cells as well as in primary astrocytes and microglia
      from cortices of rat fetuses. Down-regulation of MHC class II proteins was
      predominantly observed in parasite-positive, but not parasite-negative, host
      cells of T. gondii-infected cell cultures. MHC class II transcript levels induced
      by IFN-gamma alone or in combination with TNF-alpha were also clearly diminished
      after parasitic infection. Furthermore, T. gondii dose-dependently down-regulated
      the transcript levels of the class II transactivator CIITA. These results suggest
      that T. gondii partially evade CD4+-mediated intracerebral immune responses, a
      mechanism which may contribute to long-term persistence of the parasite within
      the CNS.

PMID- 12507769
TI  - Autoreactive T cells promote post-traumatic healing in the central nervous
      system.
AB  - In general, autoimmune responses are considered harmful to the host. In the best
      defined model of autoimmune disease, murine experimental allergic
      encephalomyelitis (EAE), for example, brain-protein-specific autoimmune responses
      of both major classes, type-1 and type-2, have been implicated in causing brain
      pathology. We induced type-1 and type-2 autoimmunity to myelin oligodendrocyte
      protein (MOG) in C57.BL/6 mice. Instead of using pertussis toxin (PTX) to open
      the blood-brain barrier (BBB), which is the classic procedure, we set an aseptic
      cerebral injury (ACI) to see what the consequences of pre-primed, autoreactive
      type-1 and type-2 memory T cells gaining access to the brain in the course of
      sterile tissue injury would be. Neither of these autoimmune response types
      induced pathology; on the contrary, both accelerated re-vascularization and post
      traumatic healing. The data suggest that induction of either type-1 or type-2
      autoimmune responses is not inherently noxious to the host, but can have
      beneficial effects on tissue repair. Autoimmune pathology may develop only if
      molecules of microbial origin such as pertussis toxin additionally induce the
      "infectious nonself/danger" reaction in the antigen-presenting cells (APC) of the
      target organ itself.

PMID- 12507770
TI  - Differential expression of class I MHC mRNA in the hypothalamus of Lewis and
      Fischer rats.
AB  - The expression of class I major histocompatibility complex (MHC) mRNA was
      compared in the brains of inflammatory susceptible, hypothalamic-pituitary
      adrenal (HPA)-axis blunted Lewis rats and inflammatory resistant, HPA-axis
      hyperresponsive Fischer rats by quantitative in situ hybridization following
      lipopolysaccharide (LPS) or vehicle administration. Lewis rats showed lower
      levels of class I MHC in the hypothalamic paraventricular nucleus (PVN) and
      retrochiasmatic area (RCA) compared to Fischer rats under both vehicle and LPS
      conditions. No differences were detected in other brain structures. Differential
      class I MHC expression in Lewis rats suggests an alteration in mechanisms related
      to cellular activity of neuroendocrine cells rather than alterations specific to
      neuroendocrine molecules.

PMID- 12507771
TI  - Microglial function in human APOE3 and APOE4 transgenic mice: altered arginine
      transport.
AB  - The APOE4 genotype is a known risk factor for Alzheimer's disease (AD) and is
      associated with poorer outcomes after neuropathological insults. To understand
      APOE's function, we have examined microglia, the CNS specific macrophage, in
      transgenic mice expressing the human APOE3 and APOE4 gene allele. Our data
      demonstrate that arginine uptake is enhanced in APOE4 microglia compared to APOE3
      microglia. The increased arginine uptake in APOE4 Tg microglia is associated with
      an increased expression of mRNA for cationic amino acid transporter-1 (Cat1), a
      constuitively expressed member of the arginine selective transport system (the y+
      transport system) found in most cells. The macrophage-associated transporter,
      cationic amino acid transporter 2B (Cat2B) did not demonstrate a change in mRNA
      expression. This change in microglial arginine transport suggests a potential
      impact of the APOE4 gene allele on those biochemical pathways such as NO
      production or cell proliferation to which arginine contributes.

PMID- 12507772
TI  - Galanin down-regulates microglial tumor necrosis factor-alpha production by a
      post-transcriptional mechanism.
AB  - The neuropeptide galanin (GAL) is up-regulated following neuronal axotomy or
      inflammation. Since other neuropeptides act as immunomodulatory agents, we sought
      to determine whether GAL might affect the murine microglial cell line BV2, which
      expresses the GAL2 receptor. Even at very low concentrations, GAL inhibited tumor
      necrosis factor-alpha (TNF alpha) release but not TNF alpha mRNA levels in LPS
      stimulated BV2 cells. Northern blot analysis showed that GAL inhibited the
      addition of a poly(A) tail, and stability assays showed that it also destabilized
      TNF alpha mRNA. Thus, GAL inhibits TNF alpha production by a post-transcriptional
      mechanism that both prevents the efficient addition of the poly(A) tail and
      accelerates TNF alpha mRNA degradation.

PMID- 12507773
TI  - Expression of AMPA-type glutamate receptors in HEK cells and cerebellar granule
      neurons impairs CXCL2-mediated chemotaxis.
AB  - We find that cerebellar granule neurons (CGN) obtained from newborn rats (p3)
      migrate in response to both CXC chemokine ligand-2 (CXCL2) and -12 (CXCL12),
      while CGN from p7 rats are unresponsive to CXCL2. The expression of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptor 1 (GluR1)
      greatly impairs the chemotaxis induced by CXCL2 in CXCR2-expressing HEK cells. By
      immunoprecipitation, we show that CXCR2 is associated with AMPA receptors
      (AMPARs) in p7 CGN, and with GluR1 co-expressed in HEK cells. Taken together,
      these results suggest that the association between CXCR2 and AMPARs results in
      the inhibition of CXCL2-dependent chemotaxis, and may represent a molecular
      mechanism underlying the modulation of nerve cell migration.

PMID- 12507774
TI  - Enhanced humoral response in kappa-opioid receptor knockout mice.
AB  - Opiates are major analgesics and addictive drugs described also as
      immunomodulators. Here, we investigated the contribution of kappa-opioid receptor
      (KOR) activity in immunity in vivo by studying immune responses in KOR knockout
      mice. These animals displayed a modest reduction in thymus cellularity and CD4(+)
      cell ratio, parallel to a slight increase in immature CD4(+)CD8(+) lymphocytes.
      In spleen, KOR null animals showed augmented cell number with no change in cell
      distribution. T and B lymphocyte proliferative capabilities in vitro, Natural
      Killer activity and steady-state Ig levels were unchanged in KOR-/- mice. We
      immunized the mice with the antigen keyhole limpet hemocyanin (KLH). Compared to
      wild-type (WT) mice, KOR-/- animals produced significant higher levels of antigen
      specific total Ig, IgM, IgG1 and IgG2a antibodies. This enhancement of humoral
      activity was not observed in mu-opioid receptor and delta-opioid receptor
      knockout animals. These results show that endogenous activation of kappa-opioid
      receptors may exert a tonic inhibition of antibody (Ab) response.

PMID- 12507775
TI  - The production of nitric oxide in EL4 lymphoma cells overexpressing growth
      hormone.
AB  - Growth hormone (GH) is produced by immunocompetent cells and has been implicated
      in the regulation of a multiplicity of functions in the immune system involved in
      growth and activation. However, the actions of endogenous or lymphocyte GH and
      its contribution to immune reactivity when compared with those of serum or
      exogenous GH are still unclear. In the present study, we overexpressed lymphocyte
      GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role
      of endogenous GH in nitric oxide (NO) production and response to genotoxic
      stress. Western blot analysis demonstrated that the levels of GH increased
      approximately 40% in cells overexpressing GH (GHo) when compared with cells with
      vector alone. The results also show a substantial increase in NO production in
      cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L
      NMMA), an L-arginine analogue that competitively inhibits all three isoforms of
      nitric oxide synthase (NOS). No evidence was obtained to support an increase in
      peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS
      activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS
      protein expression, whereas endothelial nitric oxide synthase and neuronal nitric
      oxide synthase protein levels were essentially unchanged. In addition, cells
      overexpressing GH showed increased arginine transport ability and intracellular
      arginase activity when compared with control cells. GH overexpression appeared to
      protect cells from the toxic effects of the DNA alkylating agent methyl
      methanesulfonate. This possibility was suggested by maintenance of the
      mitochondrial transmembrane potential in cells overexpressing GH when compared
      with control cells that could be blocked by L-NMMA. Taken together, the data
      support the notion that lymphocyte GH, independently of the GH receptor, may play
      a key role in the survival of lymphocytes exposed to stressful stimuli via the
      production of NO.

PMID- 12507776
TI  - IL-2 gene knockout affects T lymphocyte trafficking and the microglial response
      to regenerating facial motor neurons.
AB  - Following facial nerve axotomy in mice, T cells cross the intact blood-brain
      barrier (BBB), home to nerve cell bodies in the facial motor nucleus (FMN), and
      augment neuroregenerative processes. The pivotal T cell immunoregulatory
      cytokine, IL-2, appears to have bidirectional effects on neuronal and microglial
      cell function, suggesting rival hypotheses that IL-2 could either enhance or
      disrupt processes associated with regeneration of axotomized facial motor
      neurons. We tested these competing hypotheses by comparing the effect of facial
      nerve axotomy on C57BL/6-IL-2(-/-) knockout and C57BL/6-IL-2(+/+) wild-type
      littermates. Since IL-2 may also be produced endogenously in the brain, we also
      sought to determine whether differences between the knockout and wild-type mice
      were attributable to loss of IL-2 gene expression in the CNS, loss of peripheral
      sources of IL-2 and the associated effects on T cell function, or a combination
      of these factors. To address this question, we bred novel congenic mice with the
      SCID mutation (mice lacking T cell derived IL-2) that were homozygous for either
      the IL-2 knockout or wild-type gene alleles (C57BL/6scid-IL-2(-/-) and
      C57BL/6scid-IL-2(+/+) littermates, respectively). Groups were assessed for
      differences in (1) T lymphocytes entering the axotomized FMN; (2) perineuronal
      CD11b(+) microglial phagocytic clusters, a measure of motor neuron death; and (3)
      activated microglial cells as measured by MHC-II positivity. C57BL/6-IL-2(-/-)
      knockout mice had significantly higher numbers of T cells and lower numbers of
      activated MHC-II-positive microglial cells in the regenerating FMN than wild-type
      littermates, although the number of CD11b(+) phagocytic microglia clusters did
      not differ. Thus, despite the significant impairment of T cell function known to
      be associated with loss of peripheral IL-2, the increased number of T cells
      entering the axotomized FMN appears to have sufficient activity to support
      neuroregenerative processes. Congenic C57BL/6scid-IL-2(-/-) knockout mice had
      lower numbers of CD11b(+) microglial phagocytic clusters than congenic
      C57BL/6scid-IL-2(+/+) wild-type littermates, suggesting that loss of the IL-2
      gene in the CNS (and possibly the loss of other unknown sources of the gene)
      enhanced neuronal regeneration. Further study of IL-2's complex actions in
      neuronal injury may provide greater understanding of key variables that determine
      whether or not immunological processes in the brain are proregenerative.

PMID- 12507777
TI  - Suppressed clinical experimental autoimmune myasthenia gravis in bm12 mice is
      linked to reduced intracellular calcium mobilization and IL-10 and IFN-gamma
      release by acetylcholine receptor-specific T cells.
AB  - Class II MHC mutant bm12 mice have an increased resistance to experimental
      autoimmune myasthenia gravis (EAMG) compared to C57BL/6 mice. In vitro, this
      relative resistance was mainly associated with a reduced cytokine response to
      acetylcholine receptor (AChR) and its dominant pathogenic peptide alpha 146-162,
      whereas the response to the epitope alpha 111-126 remained intact. Calcium
      mobilization after stimulation of AChR-immune T cells with AChR or alpha 146-162
      peptide, but not alpha 111-126 peptide, was decreased in bm12 compared to
      C57BL/6. Thus, the reduced incidence of clinical EAMG in bm12 is linked to lower
      IFN-gamma and IL-10 release, and intracellular calcium mobilization by alpha 146
      162-specific T cells.

PMID- 12507778
TI  - Selective increase in TNF alpha permeation across the blood-spinal cord barrier
      after SCI.
AB  - We generated a novel mouse model of spinal cord injury (SCI) by hemisection of
      the right L1 lumbar spinal cord, measured the permeability of the blood-spinal
      cord barrier (BSCB), and tested the hypothesis that tumor necrosis factor alpha
      (TNF alpha) penetrates the injured BSCB by an enhanced transport system. SCI
      produced stereotypical sensorimotor deficits resembling the classically described
      Brown-Sequard syndrome. Disruption of the BSCB was reflected by increased spinal
      cord uptake of radiolabeled albumin from blood; this was transient (immediately
      after SCI) and confined to the lumbar spinal cord. By contrast, specific increase
      in the entry of TNF alpha was detected in brain, cervical, thoracic, and lumbar
      spinal cord at 1 week after SCI, in addition to its immediate and transient
      increase consistent with barrier disruption. Lack of a second peak of increase in
      the entry of IL1 beta further supported the specificity of the TNF alpha
      response. Moreover, enhanced uptake of radiolabeled TNF alpha was suppressed by
      excess non-radiolabeled TNF alpha, indicating competition of entry via the known
      transport system for TNF alpha. Therefore, upregulation of the transport system
      after SCI probably mediates the increased permeation of TNF alpha across the
      BSCB. Enhanced entry of TNF alpha at 1 week after SCI was concurrent with
      sensorimotor and gait improvement of the mouse. We conclude that SCI by lumbar
      hemisection activates the transport system for TNF alpha at the BBB and suggest
      that selective permeation of TNF alpha may facilitate functional recovery.

PMID- 12507779
TI  - Monocyte chemoattractant protein 1 and chemokine receptor CCR2 productions in
      Guillain-Barre syndrome and experimental autoimmune neuritis.
AB  - Infiltration of activated lymphocytes and monocytes is a key phenomenon in the
      pathogenesis of Guillain-Barre syndrome (GBS) and experimental autoimmune
      neuritis (EAN). To investigate the role of chemokines, we determined the blood
      and nerve tissue expression of monocyte chemoattractant protein 1 (MCP-1), a
      major chemoattractant of monocytes and activated lymphocytes, and its receptor
      CCR2 in GBS and EAN. MCP-1 circulating levels (ng/ml) in GBS were increased at
      the time of progression, peaked at the time of plateau and normalized with
      recovery. MCP-1 circulating levels were the highest in the most disabled
      patients. The number of circulating CCR2 positive cells was lower in patients
      with GBS than in healthy subjects (p<0.004). In GBS, MCP-1 expression was
      observed in epineurial and endoneurial vessels, on infiltrating cells, Schwann
      cells and in the endoneurial extracellular matrix. Some CCR2 positive cells were
      observed in nerve biopsies of GBS patients. In EAN, a slight positivity for MCP-1
      was observed in the sciatic nerve. There was no circulating CCR2 positive cells.
      However, at the time of plateau, a conspicuous infiltration of CCR2 positive
      cells was observed in the sciatic nerve that was no longer observed at the time
      of recovery. These results suggest that MCP-1 and CCR2 may participate to the
      recruitment of circulating mononuclear cells in nerve tissue in EAN and GBS.

PMID- 12507780
TI  - Cytokine profile in patients with multiple sclerosis following vitamin D
      supplementation.
AB  - Multiple sclerosis (MS) patients were randomized, in a double blind design, and
      placed into either a vitamin D supplemented group or a placebo control group. As
      expected, serum 25-hydroxyvitamin D levels increased significantly following 6
      month vitamin D supplementation (17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6
      months). Vitamin D supplementation also significantly increased serum
      transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to
      295+/-40 pg/ml 6 months later. Placebo treatment had no effect on serum TGF-beta
      1 levels. Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and
      interleukin (IL)-13 were not different following vitamin D supplementation. IL-2
      mRNA levels decreased following vitamin D supplementation but the differences did
      not reach significance. Vitamin D supplementation of MS patients for 6 months was
      associated with increased vitamin D status and serum TGF-beta 1.

PMID- 12507781
TI  - CTLA4 is associated with susceptibility to multiple sclerosis.
AB  - We comprehensively screened CTLA4 for novel genetic variations in patients with
      MS. We studied genetic variations by association methods in a population-based
      sample of 122 sporadic patients with MS and 244 age-, gender- and ethnicity
      matched controls, and by linkage and family-based association methods in 395
      individuals from 59 American multiplex pedigrees with 141 affected individuals.
      Being homozygous for AT(8) (common) allele of the 3'(514) microsatellite (OR:
      1.69; CI: 0.99-2.86) and for the common 5'(318)*C/E1(49)*A/3'(514*AT(8) haplotype
      (OR: 1.96; CI: 1.13-3.39) was associated with increased susceptibility to MS in
      Olmsted County. The genotype frequencies of other individual polymorphisms were
      not significantly different between cases and controls. A pooled analysis of
      association studies revealed an odds ratio of 1.28 (95% CI: 1.01-1.63; p=0.043)
      for 5'(-318)*C homozygotes and 1.28 (95% CI: 1.08-1.51; p=0.005) for the
      3'(514)*AT(8) allele. We did not detect linkage with MS susceptibility in
      multiplex families. We did not find a strong association with age at onset,
      disease course or severity. CTLA-4 is associated with susceptibility to MS.

PMID- 12507782
TI  - Inflammation markers in relation to cognition in a healthy aging population.
AB  - The relation between serum inflammatory protein levels and cognitive performance
      was investigated in a healthy population. Individuals were tested during 6 years
      of follow-up. Serum concentrations of 10 inflammatory proteins were correlated to
      cognitive speed (Letter-Digit Coding Test, LDCT), attention and information
      processing (Stroop) and memory (Word Learning). Haptoglobin levels at baseline
      correlated negatively with cognitive performance on the Stroop and Word Learning
      Recall test over the 6 years follow-up period. C-reactive protein (CRP) levels at
      baseline correlated negatively with performance on the Word Learning tests over
      the 6 years follow-up period. Thus, relatively high concentrations of haptoglobin
      and C-reactive protein may be indicative for impaired cognitive performance.

PMID- 12507783
TI  - TGF-beta 1 and IL-10 modulate IL-1 beta-induced membrane and soluble ICAM-1 in
      human myoblasts.
AB  - We have previously shown that interleukin (IL)-1 beta and other inflammatory
      cytokines are able to induce the expression of membrane and soluble intercellular
      adhesion molecule (ICAM)-1 on human myoblasts. In this paper we found that IL-10
      and transforming growth factor (TGF)-beta 1 are able to prevent IL-1 beta-induced
      membrane and soluble ICAM-1 protein expression on human myoblasts, with different
      time courses. The effect of both cytokines is associated to a reduction in ICAM-1
      mRNA. Our findings suggest that IL-10 and TGF-beta 1 are able to influence the
      inflammatory process in muscle tissue at least in part by means of control of
      membrane and soluble ICAM-1.

PMID- 12507784
TI  - Expression ratios of the Bcl-2 family proteins and disease activity in multiple
      sclerosis.
AB  - There is emerging evidence that failure of apoptosis (programmed cell death) of
      potentially pathogenic T lymphocytes may be involved in the pathogenesis of
      multiple sclerosis (MS). The commitment of T lymphocytes to die is partly
      regulated by the Bcl-2 family proteins, which act as a checkpoint upstream of
      mitochondrial dysfunction. These proteins include the death antagonists Bcl-2 and
      Bcl-X(L), and death agonists Bax and Bad. Recent studies suggest that altered
      expression of Bcl-2 family proteins in T lymphocytes is involved in promoting
      cellular resistance to apoptosis in patients with MS. However, the relationship
      between these alterations in Bcl-2 proteins expression and clinical disease
      activity has not yet been evaluated. In this study, we analyzed the expression
      ratios of pro- to anti-apoptosis Bcl-2 family proteins in patients with
      clinically active MS and compared results to corresponding ratios in patients
      with stable MS and relevant control groups. We observed a significant reduction
      in the expression ratios of pro- to anti-apoptosis Bcl-2 members in peripheral
      lymphocytes from patients with active MS when compared to corresponding ratios in
      patients with stable MS or other controls. This imbalance in the expression
      ratios of pro- and anti-apoptosis proteins was functionally active in reducing
      cellular susceptibility to apoptosis in active MS. It also correlated with
      clinical features of disease activity, such as the number of gadolinium-enhancing
      MRI lesions and clinical relapses. Our findings indicate that dysregulated
      expression of Bcl-2 family proteins in peripheral lymphocytes is a feature of
      clinically active multiple sclerosis.

PMID- 12507785
TI  - CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to
      endothelium.
AB  - Recent evidence suggests that interactions between CD40 on antigen presenting
      cells (APC) and CD40L on T cells generate signals that result in the activation
      of APC. In this study, the expression and function of CD40 was investigated in
      primary cultures of human brain microvessel endothelial cells (HBMEC). Results
      revealed constitutive expression of CD40 on untreated HBMEC. Stimulation with TNF
      alpha, IFN-gamma, LPS or combination of TNF-alpha and IFN-gamma significantly
      upregulated CD40. The majority of CD40 molecules were localized on the apical
      surface of EC. Incubation of HBMEC with soluble CD40L resulted in increased
      expression of the adhesion molecules E-selectin, VCAM-1 and ICAM-1. Consequently,
      the adhesion of both resting and anti-CD3 activated CD4+ T lymphocytes to CD40L
      treated HBMEC was significantly increased compared to unstimulated EC. The
      expression of CD40 by cerebral endothelium, and endothelial cell activation
      following binding of CD40 to its ligand, CD40L, suggest a potential mechanism by
      which activated CD40L expressing T cells could enhance adhesion and migration of
      inflammatory cells across the blood-brain barrier (BBB) to sites of inflammation
      in the human central nervous system (CNS).

PMID- 12507786
TI  - Use of correspondence discriminant analysis to predict the subcellular location
      of bacterial proteins.
AB  - Correspondence discriminant analysis (CDA) is a multivariate statistical method
      derived from discriminant analysis which can be used on contingency tables. We
      have used CDA to separate Gram negative bacteria proteins according to their
      subcellular location. The high resolution of the discrimination obtained makes
      this method a good tool to predict subcellular location when this information is
      not known. The main advantage of this technique is its simplicity. Indeed, by
      computing two linear formulae on amino acid composition, it is possible to
      classify a protein into one of the three classes of subcellular location we have
      defined. The CDA itself can be computed with the ADE-4 software package that can
      be downloaded, as well as the data set used in this study, from the Pole Bio
      Informatique Lyonnais (PBIL) server at http://pbil.univ-lyon1.fr.

PMID- 12507787
TI  - Partitioning large-sample microarray-based gene expression profiles using
      principal components analysis.
AB  - Principal components analysis (PCA) is useful for reproducing the total variation
      among hundreds or thousands of continuously-scaled variables with a much smaller
      number of unobservable variables called 'latent factors'. The CLUSFAVOR computer
      program was used to implement PCA for identifying groups of genes with similar
      expression profiles from a large number of genes used on DNA microarrays. This
      paper describes the principal components solution to the factor model of the
      correlation matrix R, calculation of eigenvalues and eigenvectors of R,
      extraction of factors, and calculation of factor loadings and identification of
      genes with similar loading patterns to construct groups of genes with similar
      expression profiles. With regard to extraction of factors, it was found that more
      than 90% of the total variance in input data could be accounted for by extracting
      factors whose eigenvalues exceed unity. Bipolar factors containing strong
      positive and negative loadings can also be used for identifying two unique groups
      of genes, since expression profiles of genes that load positive are unlike
      expression profiles of genes that load negative on the same factor. While PCA
      does not provide the absolute answer to a multidimensional problem, it
      nevertheless can provide a heuristic with which natural groupings of genes with
      similar expression profiles can be assembled. While cluster analysis essentially
      generates a single dendogram (tree branch) containing every gene in the input
      data, PCA can be used to assemble gene expression profiles that strongly
      correlate with the latent factors accounting for a majority of total variance.
      Example results for CLUSFAVOR computer program runs are provided.

PMID- 12507788
TI  - An automated method to position prosthetic components within multiple anatomical
      spaces.
AB  - The level of fit and fill of a stem in the host femur is the most critical factor
      for the mechanical stability and success of the prosthesis. It would be useful to
      have a simulation tool able to investigate the anatomical compatibility of a new
      implant in a large library of femoral anatomies in the early phases of the design
      process. In order to realise this tool, it is necessary to develop an automatic
      method for the positioning of the stem in a database of anatomies. The aim of
      this study was to develop and evaluate a method for the automatic positioning of
      the stem geometry in the anatomical CT dataset. Two different strategies were
      considered: a completely automatic registration technique and a semi-automatic
      method based on an anatomical referencing. The two procedures were compared to
      the manual positioning obtained by an expert surgeon in a set of nine CT
      datasets. For both methods in each femur the positioning and the orientation of
      the stem were good. The results showed a better level of fitting for the
      automatic method, while the shift of the hip joint centre was lower for the
      anatomical referencing technique. However, the anatomical referencing method
      requires a higher computational effort without being significantly better than
      the automatic method. For this reason, the automatic method should be chosen to
      develop the automatic positioning of a stem in a database of anatomies.

PMID- 12507789
TI  - Fast algorithm for 3-D vascular tree modeling.
AB  - In this short paper, accelerated three-dimensional computer simulations of
      vascular trees development, preserving physiological and haemodynamic features,
      are reported. The new computation schemes deal: (i). with the geometrical
      optimization of each newly created bifurcation; and (ii). with the recalculation
      of blood pressures and radii of vessels in the whole tree. A significant decrease
      of the computation time is obtained by replacing the global optimization by the
      fast updating algorithm allowing more complex structure to be simulated. A
      comparison between the new algorithms and the previous one is illustrated through
      the hepatic arterial tree.

PMID- 12507790
TI  - A human tissue and data resource: an overview of opportunities, challenges, and
      development of a provider/researcher partnership model.
AB  - As we continue to strive to apply the findings of in vitro and animal studies to
      human disease and transition from genomics to proteomics, we will experience an
      ever-increasing need for human tissues. A web based system that provides access
      to tissues repositories and associated data will best facilitate the access to
      these vital resources and the application of research information to human
      disease treatment. There are organizational and design requirements that must be
      addressed in the implementation of the infrastructures that are needed to
      implement such a system, with special attention paid to the protection of patient
      anonymity. This report describes the implementation of a prototype human tissue
      network in the hope of encouraging implementation of similar systems among other
      consortia of providers and researchers.

PMID- 12507791
TI  - CoLD: a versatile detection system for colorectal lesions in endoscopy video
      frames.
AB  - In this paper, we present CoLD (colorectal lesions detector) an innovative
      detection system to support colorectal cancer diagnosis and detection of pre
      cancerous polyps, by processing endoscopy images or video frame sequences
      acquired during colonoscopy. It utilizes second-order statistical features that
      are calculated on the wavelet transformation of each image to discriminate
      amongst regions of normal or abnormal tissue. An artificial neural network
      performs the classification of the features. CoLD integrates the feature
      extraction and classification algorithms under a graphical user interface, which
      allows both novice and expert users to utilize effectively all system's
      functions. It has been developed in close cooperation with gastroenterology
      specialists and has been tested on various colonoscopy videos. The detection
      accuracy of the proposed system has been estimated to be more than 95%. As it has
      been resulted, it can be used as a supplementary diagnostic tool for colorectal
      lesions.

PMID- 12507792
TI  - Interactions with 3D isotropic and homogeneous radiation fields: a Monte Carlo
      simulation algorithm.
AB  - Monte Carlo techniques have become important tools for many biomedical
      applications. Many of these involve simulations of radiation fields that rely on
      the isotropy and homogeneity of the radiation source. The current study proposes
      a general algorithm to simulate such a radiation field around a fixed object. The
      idea is to surround the object with a sphere and to limit the source of radiation
      to the surface of that sphere. To insure the isotropy of the radiation source,
      each point on the sphere surface as seen from the object defines a direction at
      which a unidirectional field of particles is created. The combination of all
      unidirectional fields approaching from all points on the source sphere creates
      the effect of an isotropic and homogeneous radiation source. The algorithm is
      first presented without mathematical detail. Next, the expressions for the
      position and direction of the particles that compose the field are derived using
      analytical geometry. The radius of the source sphere is the only parameter needed
      for this algorithm. The randomness of each particle is simulated by the choice of
      four random numbers. Two algorithms using these analytical results are proposed,
      and an example of a C program is given for each. Both algorithms can be easily
      adapted to any situation that involves the Monte Carlo simulation of radiation
      interactions of a fixed object immersed within an isotropic and homogeneous
      radiation field.

PMID- 12507793
TI  - Computer simulation of the skin reflectance spectra.
AB  - The reflectance spectra of the human skin in visible and near-infrared (NIR)
      spectral region have been calculated using the Monte Carlo technique, and the
      specular and internal reflection on the medium surface is taken into account.
      Skin is represented as a complex inhomogeneous multi-layered highly scattering
      and absorbing medium. The model takes into account variations in spatial
      distribution of blood, index of blood oxygen saturation, volume fraction of water
      and chromophores content. The simulation of the skin tissues optical properties
      and skin reflectance spectra are discussed. Comparison of the results of
      simulation and in vivo experimental results are given.

PMID- 12507794
TI  - Drugs and adolescent girls.

PMID- 12507795
TI  - The application of psychosocial factors to HIV risk among Belizean adolescents.

PMID- 12507796
TI  - The relationship between employment and substance use among students aged 12 to
      17.
AB  - PURPOSE: To examine the association between employment status and substance use
      among students aged 12 to 17 years. METHODS: Secondary analysis of data from the
      1995 and 1996 National Household Surveys on Drug Abuse was conducted. The survey
      is a primary source of data on licit and illicit drug use among
      noninstitutionalized Americans aged 12 years or older. Participants are
      interviewed at their places of residence. Multiple logistic regression procedures
      yielded estimated associations. RESULTS: About one in six adolescents reported
      both going to school and holding a job. Approximately one-fourth of students
      smoked cigarettes, and one-third consumed alcohol in the past year. An estimated
      1.6% of students were current heavy cigarette smokers, and 2.6% were current
      heavy alcohol users. One-year prevalence estimates of any illicit drug use and
      heavy illicit drug use were 16.7% and 1.8%, respectively. Among students employed
      full time, prevalence estimates increased to 9.7% for heavy cigarette smoking,
      13.1% for heavy alcohol use, 38.1% for any illicit drug use, and 5.0% for heavy
      illicit drug use. Logistic regression analyses supported relatively high rates of
      cigarette use, alcohol use, illicit drug use, and heavy substance use among
      working students. Mental health problems, especially externalizing behavioral
      syndromes, were found to coexist with the use and heavy use of substances. The
      observed associations varied somewhat by gender. CONCLUSIONS: The workplace may
      be an appropriate venue for establishing substance use prevention and early
      intervention programs focused on younger workers, including adolescents who work
      part time.

PMID- 12507797
TI  - Drug testing athletes to prevent substance abuse: background and pilot study
      results of the SATURN (Student Athlete Testing Using Random Notification) study.
AB  - PURPOSE: To assess the deterrent effect of mandatory, random drug testing among
      high school (HS) athletes in a controlled setting. METHODS: Two high schools, one
      with mandatory drug testing (DT) consent before sports participation, and a
      control school (C), without DT, were assessed during the 1999-2000 school year.
      Athletes (A) and nonathletes (NA) in each school completed confidential (A) or
      anonymous (NA) questionnaires developed for this study, respectively, at the
      beginning and end of the school year. Positive alcohol or drug tests required
      parent notification and mandatory counseling without team or school suspension.
      Thirty percent of the DT athletes were tested. Data were analyzed using the end
      of the school year measure, adjusted for the initial questionnaire results.
      Demographics of the athlete sample revealed that mean age was 15.5 years with
      81.5% white, 9.6% Hispanic, 4.5% Asian, 2.6% American Indian/Native Alaskan, 1.3%
      African-American, and 1.3% Native Hawaiian/Pacific Islander. RESULTS: A (n = 276)
      and NA (n = 507) were assessed at the beginning (baseline) and at the end of the
      school year (A, n = 159; NA, n = 338). The past 30-day index of illicit drugs (4
      fold difference) and athletic enhancing substances (3-fold difference) were lower
      (p < .05) among DT athletes at follow-up without difference in alcohol use.
      However, most drug use risk factors, including norms of use, belief in lower risk
      of drugs, and poorer attitudes toward the school, increased among DT athletes (p
      < .05). Although a reduction in the illicit drug use index was present among
      nonathletes at the DT school, at the end of the school year, it did not achieve
      statistical significance (p < .10). CONCLUSIONS: Random DT may have reduced
      substance use among athletes. However, worsening of risk factors and small sample
      size suggests caution to this drug prevention approach. A larger long-term study
      to confirm these findings is necessary.

PMID- 12507798
TI  - Taking up binge drinking in college: the influences of person, social group, and
      environment.
AB  - PURPOSE: To identify person, social group, and environmental factors associated
      with uptake of binge drinking among a national sample of college students.
      METHODS: Using self-reported responses of students in the 1999 Harvard School of
      Public Health College Alcohol Study (CAS), we regressed conceptually important
      predictors of binge drinking onto a dichotomized variable describing uptake in
      the freshman year. This was a random sample of full-time undergraduates provided
      by the registrar at each participant school (n = 119). For this study, we
      analyzed data describing a subset of the total sample comprising first year
      students aged < or =19 years, excluding transfers (n = 1894). The student CAS is
      a 20-page voluntary, anonymous mailed questionnaire containing student reports
      about their alcohol and substance use, school activities, and background
      characteristics. Analyses included univariate and multivariate logistic
      regression adjusting for school response rate and using the Generalized
      Estimating Equations (GEE) in the Statistical Analysis Software package to handle
      the within-college clustering owing to the sampling scheme. RESULTS: College
      students who reported that they were exposed to "wet" environments were more
      likely to engage in binge drinking than were their peers without similar
      exposures. Wet environments included social, residential, and market surroundings
      in which drinking is prevalent and alcohol cheap and easily accessed. Findings
      held up in multivariate analyses that included variables describing person and
      social group characteristics. Students who picked up binge drinking in college
      also were more likely than their peers to report inflated definitions of binge
      drinking and more permissive attitudes about appropriate ages for legal
      consumption. CONCLUSIONS: Binge drinking can either be acquired or avoided in
      college among students who report they did not binge drink in high school.
      Reducing college binge uptake may require efforts to limit access/availability,
      control cheap prices, and maximize substance free environments and associations.

PMID- 12507799
TI  - Effects of pro- and anti-tobacco advertising on nonsmoking adolescents'
      intentions to smoke.
AB  - PURPOSE: To determine the effects of pro- and anti-tobacco advertising on
      nonsmoking adolescents' intention to smoke in a single cohort. METHODS: All ninth
      graders at seven public high schools were invited to participate in a study on
      adolescent tobacco use; 59.0% participated (n = 1229; active positive parental
      consent required). Adolescents who self-identified as never having smoked even a
      puff of a cigarette (n = 512) completed a self-administered questionnaire that
      included questions on intention to smoke in the near future and tobacco
      advertising. Independent variables used to predict intention included exposure
      to, recognition of, and receptivity and attitudes toward pro-tobacco and anti
      tobacco advertising. Potential confounding variables included gender,
      race/ethnicity, smoking influences (adult household members, siblings, and
      friends), socioeconomic status, stress, and depression. Data analysis used
      logistic regression. RESULTS:  DEMOGRAPHICS: 50.5% female, average age 14.9 +/-
      0.4 years old at baseline, and varied race. Those variables found to be
      significant predictors of intention to smoke included: (positive, or increased
      intention) recognition of brand of favorite advertisement, willingness to use or
      wear tobacco-branded products, stress, and having friends who smoke and
      (negative, or decreased intention) agreement with anti-tobacco advertising and
      having a live-in father who smokes. CONCLUSIONS: Although anti-tobacco
      advertising has a protective effect, it was unable to counteract the effects of
      pro-tobacco advertising in the same cohort.

PMID- 12507800
TI  - Body modification and substance use in adolescents: is there a link?
AB  - PURPOSE: To describe the characteristics of body modification among adolescents
      and to determine whether adolescents who engage in body modification are more
      likely to screen positive for alcohol and other drug problems than those who do
      not. METHODS: Adolescents aged 14 to 18 years presenting to an urban adolescent
      clinic for routine health care completed a questionnaire about body modification
      and a substance use assessment battery that included the 17-item Problem Oriented
      Screening Instrument for Teenagers Alcohol/Drug Use and Abuse Scale (POSIT-ADS).
      Body modification was defined as piercings (other than one pair of bilateral
      earlobe piercings in females), tattoos, scarification, and branding. Problem
      substance use was defined as a POSIT-ADS score > or =1. Data were analyzed using
      logistic regression to determine whether the presence of body modification was an
      independent predictor of problem substance use. RESULTS: The 210 participants had
      a mean (+/- SD) age of 16.0 (+/- 1.4) years and 63% were female. One hundred
      adolescents (48%) reported at least one body modification; girls were more likely
      than boys to have body modification (59% vs. 28%, p < or = .0005). Ninety (42%)
      reported piercings, 22 (10%) tattoos, 9 (4%) scarification, and 1 (< 1%)
      branding; 21 (10%) had more than one type of body modification. These were in a
      variety of locations, most commonly the ear and the nose (piercings) or the
      extremities (tattoos). One-third of the sample (33%) screened positive for
      problem substance use on the POSIT-ADS questionnaire. Controlling for age,
      adolescents with body modification had 3.1 times greater odds of problem
      substance use than those without body modification (95% CI 1.7, 5.8).
      CONCLUSIONS: Body modification was associated with self-reported problem alcohol
      and other drug use among middle adolescents presenting for primary care. More
      research is needed to determine the clinical and sociocultural significance of
      body modification and its relationship to substance use in this population.

PMID- 12507801
TI  - Tobacco use as a predictor of illicit drug use and drug-related problems in
      Colombian youth.
AB  - PURPOSE: To examine the extent to which personality and peer factors mediate the
      relationship between early cigarette use and later illicit drug use, as well as
      associated drug use problems, in a population of Colombian adolescents. METHODS:
      A longitudinal study (2-year interval), using face-to-face structured interviews
      was begun in 1996 using a community-based sample, randomly selected from census
      data in three cities in Colombia, South America. The participants were 2837
      adolescents with a mean age of 15.0 (SD +/- 1.6) years at time 1 (T1). Males
      comprised 52% of the sample and 65% resided with two parents. Approximately 78%
      (N = 2226) completed the second structured interview 2 years later (T2). The main
      outcome measures were marijuana use, other illicit drug use, and associated drug
      use problems at T2. Three series of logistic regressions were conducted. RESULTS:
      The odds of marijuana use (adjusted odds ratio [AOR] = 1.64-2.01; confidence
      interval [CI]: 1.11-2.94), other illicit drug use (AOR = 1.77-2.49; CI: 1.03
      4.19), and associated drug use problems (AOR = 2.25-3.47; CI: 1.45-5.26) at T2,
      was increased two- to three-fold among adolescents reporting cigarette use at T1,
      with control on the demographic, personality, and peer factors, as well as T1
      drug use variables. CONCLUSIONS: Earlier adolescent cigarette smoking was
      directly associated with later marijuana use, other illicit drug use, and
      problems with drug use.

PMID- 12507802
TI  - Substance use by adolescents in Cape Town: prevalence and correlates.
AB  - PURPOSE: The work reported in this paper was supported by grants from the World
      Health Organisation Programme on Substance Abuse, the United Nations Development
      Programme, the South African Medical Research Council, and the Medical Faculty
      Research Committee of the University of Cape Town.To document the prevalence
      rates for use of cigarettes, alcohol, and cannabis among high school students in
      Cape Town, and to investigate whether use of these substances is associated with
      a set of hypothesized psychosocial correlates. METHODS: A multistage sampling
      procedure produced a sample of 2930 students in grades 8 and 11 at 39 high
      schools in Cape Town, who completed a self-administered questionnaire. The
      questionnaire contained items about whether the students had used various
      substances and that addressed the potential correlates of interest. We calculated
      prevalence rates with 95% confidence intervals and constructed a set of
      generalized estimating equations of use in the past month of cigarettes, alcohol,
      or cannabis on the hypothesized correlates. RESULTS: The prevalence rates for
      previous month (recent) use of cigarettes, alcohol, and cannabis were 27%, 31%,
      and 7%, respectively. Rates were low for black females. Recent use of each of the
      substances was significantly associated with the number of days absent and the
      number of years lived in a city. Repeating a grade was significantly associated
      with previous month use of cigarettes and alcohol by colored (derived from Asian,
      European, and African ancestry) students and alcohol use by black grade 8
      students (race classifications "colored" and "black" are as defined by the
      repealed population Registration Act of 1950). Not being raised by both parents
      was significantly associated with cigarette smoking by black and colored
      students, alcohol use by colored students, and cannabis use by female students.
      It was inversely associated with cigarette use by black students. CONCLUSIONS: It
      is necessary to identify the factors that protect black female adolescents from
      substance use. It is important to address demographic factors such as race
      classification and gender analytically if one is to avoid obscuring differences
      among groups.

PMID- 12507803
TI  - Negative perceptions about self-control and identification with gender-role
      stereotypes related to binge eating, problem drinking, and to co-morbidity among
      adolescents.
AB  - PURPOSE: To examine the role of both positive and negative styles of self
      control, and gender-role stereotypes in binge eating and problem drinking.
      METHOD: Participants were 428 adolescent boys and 555 girls from predominantly
      Anglo-Australian backgrounds who attended regional state schools in New South
      Wales, Australia. Students completed standardized questionnaires that assessed
      problem drinking, binge eating, self-control styles, and identification with
      gender-role stereotypes. ANOVA and post hoc Tukey tests were conducted to examine
      differences among adolescents who reported problems in binge eating, drinking,
      and both domains. RESULTS: Adolescents who reported eating and drinking problems
      also reported a high negative and a low positive sense of self-control coupled
      with self-identification with the traits that typically describe negative
      dimensions of gender-role stereotypes. Regardless of gender, problem drinking was
      mainly related to traits of negative masculinity (bossy, noisy aggressive, etc.)
      whereas binge eating was mainly related to negative femininity (shy, needs
      approval from others, etc.). Participants who reported eating and drinking
      symptoms recorded low scores on positive control, high scores on negative
      control, and also high scores on the negative dimensions of masculinity and
      femininity. SUMMARY: A negative and passive style of self-control coupled with an
      identification with negative dimensions of gender summarizes the type of self
      regulation that is implicated in both binge eating and problem drinking, and co
      morbid symptoms. There is a need for interventions working toward a more balanced
      gender self-concept and a positive sense of self-control.

PMID- 12507804
TI  - Resolution of vital sign instability: an objective measure of medical stability
      in anorexia nervosa.
AB  - PURPOSE: To determine the amount of time necessary for stabilization of blood
      pressure and heart rate in patients with anorexia nervosa (AN) and the percentage
      of ideal body weight (IBW) at which this occurs. METHODS: A retrospective study
      was conducted on 36 adolescent patients (33 F, 3 M) with AN, restricting type
      (Diagnostic and Statistical Manual of Mental Disorders, Fourth edition [DSM-IV]
      criteria), admitted to a specialized eating disorders unit for nutritional
      rehabilitation between October 1996 and August 1998. Mean age was 16.5 +/- 2.5
      years, range 12-23 years. Each morning, pulse and blood pressure were measured
      supine and after standing for 2 minutes using an automated blood pressure/pulse
      measuring device (Dynamap). Orthostasis was defined as a drop in systolic blood
      pressure > 20 mm Hg with or without a drop in diastolic blood pressure > 10 mm Hg
      or an increase in heart rate >20 bpm on standing. Time of resolution of
      orthostasis was defined as the day after which the patient was no longer
      orthostatic for 48 hours. RESULTS: On admission mean pulse rate was 54.4 +/- 14.8
      bpm (range 38-78) and mean pulse rate slowly increased to 70 bpm by Day 12 of
      hospitalization. On admission, 60% of patients had orthostatic pulse changes and
      with refeeding, this number increased to 85% by Day 4 of admission. The mean
      number of days until patients were no longer orthostatic was 21.6 +/- 11.1 days
      and resolution of orthostasis occurred when subjects reached 80.1 +/- 5.7% of
      IBW. Orthostatic pulse changes were more sensitive indicators of hemodynamic
      instability than orthostatic blood pressure changes and took longer to resolve.
      CONCLUSION: This study demonstrates that of patients with AN, the majority have
      orthostatic pulse changes on admission. Normalization of orthostatic pulse
      changes was achieved after approximately 3 weeks of nutritional rehabilitation
      when subjects reached 80% of their IBW. Resolution of orthostasis can be used as
      one of the objective measures to determine medical stability and readiness for
      discharge to an alternate level of care.

PMID- 12507805
TI  - Reading magazine articles about dieting and associated weight control behaviors
      among adolescents.
AB  - The purpose was to examine the sociodemographic characteristics of adolescents
      who read magazine articles about dieting/weight loss and the relationship between
      reading these types of magazine articles and psychosocial well-being and weight
      control behaviors. Dieting-related magazine exposure was associated with
      indicators of psychosocial distress and unhealthy dieting; interventions that
      address media consumption should reach out to all youth regardless of ethnic and
      social backgrounds

PMID- 12507806
TI  - Hypophosphatemia during nutritional rehabilitation in anorexia nervosa:
      implications for refeeding and monitoring.
AB  - PURPOSE: To determine the incidence of hypophosphatemia in adolescents with
      anorexia nervosa (AN) hospitalized for nutritional rehabilitation and to examine
      factors predisposing to its development. METHODS: A retrospective chart review of
      69 patients (66 female, 3 male) with AN consecutively admitted to an inpatient
      adolescent medical unit between July 1, 1998 and June 30, 2000. Mean age was 15.5
      +/- 2.4 (range 8 to 22) years and mean % ideal body weight (IBW) was 72.7 +/- 7%.
      Serum phosphorus was measured daily for 1 week and then biweekly to weekly.
      Patients were started on 1200-1400 kcal/day and calories were increased by 200
      kcal every 24-48 hours. RESULTS: Four (5.8%) patients developed moderate
      hypophosphatemia (<2.5 and > or = 1.0 mg/dl) and 15 (21.7%) had mild
      hypophosphatemia (<3.0 and > or = 2.5 mg/dl). Patients who developed moderate
      hypophosphatemia were significantly more malnourished than those who did not (p =
      0.02). Phosphorus nadirs were directly proportional to % IBW (r = 0.3, p = 0.01).
      Over three-quarters of the patients (81%) reached their phosphorus nadir within
      the first week of hospitalization. The patient with the lowest phosphorus level
      experienced short runs of ventricular tachycardia. No other severe complications
      were seen. Overall, 19 (27.5%) patients required phosphorus supplementation.
      CONCLUSIONS: Phosphorus drops to its nadir during the first week of refeeding. We
      recommend daily monitoring of serum phosphorus with supplementation as needed
      during the first week of hospitalization, especially in those who are severely
      malnourished.

PMID- 12507807
TI  - Pituitary apoplexy after leuprolide injection for ovum donation.
AB  - Patients with occult pituitary adenomas infrequently present with pituitary
      apoplexy. Precipitation of pituitary apoplexy by gonadotropin releasing hormone
      or gonadotropin releasing hormone agonists has been described. The
      pathophysiologic mechanism by which these agents induce apoplexy remains unclear.
      We describe a case of pituitary apoplexy in a young woman receiving leuprolide in
      preparation for ovum donation. Severe hyponatremia, cerebral vasospasm and
      infarction, and diabetes insipidus complicated this patient's prolonged hospital
      course. To our knowledge, pituitary apoplexy after gonadotropin releasing hormone
      agonist use for ovum donation has not been previously described. The use of
      leuprolide or other gonadotropin releasing hormone agonists for pituitary down
      regulation in conjunction with ovarian stimulation can have serious consequences
      in women harboring unrecognized pituitary adenomas. Thorough endocrine screening
      should be performed prior to initiating therapy.

PMID- 12507808
TI  - The unusual association of three autoimmune diseases in a patient with Noonan
      syndrome.
AB  - We report on a 26-year-old female affected by Noonan syndrome (NS), a congenital
      disorder characterized by various phenotypic features and congenital anomalies)
      associated with a variety of autoimmune diseases, including systemic lupus
      erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom
      described in NS and the association between this congenital disease and three
      autoimmune disorders has not been previously reported. Should the occurrence of
      autoimmune disorders in NS be confirmed, a relevant clinical and laboratory
      evaluation of NS patients should be performed in order to clarify whether the
      immune system involvement represents only an occasional event or is a feature of
      the disease.

PMID- 12507809
TI  - Administration of different antigenic forms of altered peptide ligands derived
      from HIV-1 RTase influences their effects on T helper cell activation.
AB  - Genetic hypervariability of viruses such as HIV-1 facilitates appearance of
      escape mutants for immune response. HIV-1 isolates display variant epitopes,
      which may fail to stimulate T-lymphocyte responses or act as natural T-cell
      receptor antagonists, contributing to viral persistence. We evaluated the effect
      on epitope specific T-cell reactions of different amino acid substitutions in a
      residue of the 248-262 sequence of HIV-1 reverse transcriptase (peptide 23),
      showing variability in different viral isolates. Responses against such a
      determinant have been detected in long-term nonprogressive patients. The modified
      antigenic determinant was administered either as synthetic peptide or as
      recombinant protein. Our results show that certain amino acid substitutions
      abolished peptide binding to major histocompatibility complex (MHC); other
      modifications, although not affecting the formation of the MHC/peptide complex,
      either abrogated T-cell proliferation or exhibited an antagonistic effect. The
      results suggest that residue 11 of peptide 23 exhibits a double function; its
      alteration affects both the peptide affinity for the MHC and the MHC/peptide
      complex affinity for the T-cell receptor. Furthermore, we demonstrated that
      synthetic ligands and recombinant proteins may produce distinct functional
      effects, providing evidence that synthetic peptides, compared with corresponding
      epitopes generated by intracellular processing of recombinant proteins, may bind
      to the MHC groove in a different conformation.

PMID- 12507810
TI  - Apoptotic DNA binds to HLA class II molecules inhibiting antigen presentation and
      participating in the development of anti-inflammatory functional behavior of
      phagocytic macrophages.
AB  - Resident macrophages are mainly responsible for the clearance of apoptotic cells
      from tissue by phagocytosis. Phagocytosis of apoptotic cells is not accompanied
      by activation of inflammatory mechanisms, unlike what happens when necrotic
      phenomena occur. We analyzed the effect of phagocytosis of apoptotic bodies on
      macrophage cell functions. After phagocytosis of apoptotic cells macrophages were
      unable to present an exogenous antigen to autologous antigen-specific T-cell
      lines. The inhibition was mediated by different mechanisms including binding of
      apoptotic DNA to human leukocyte antigen (HLA) class II molecules of macrophages,
      decreased expression of co-stimulatory molecules and increased secretion of tumor
      growth factor beta (TGFbeta). When dendritic cells were cultured with macrophages
      phagocytosing apoptotic cells, or with their supernatant, impaired dendritic cell
      antigen presenting activity and reduced tumor necrosis factor alpha (TNFalpha)
      secretion were found. Our results suggest that: (1) the phagocytosis of apoptotic
      bodies inhibits macrophage antigen presentation; (2) such inhibition is mediated
      by the binding of apoptotic DNA to macrophage HLA class II molecules as well as
      by the activation of biological mechanisms that induce an anti-inflammatory
      functional behavior in macrophages; and (3) macrophages phagocytosing apoptotic
      cells inhibit antigen presentation of neighboring dendritic cells via TGFbeta
      secretion. These events are likely related to the preservation of healthy tissues
      from the onset of inflammation.

PMID- 12507811
TI  - Human donor bone marrow cells induce in vitro "suppressor T cells" that
      functionally suppress autologous B cells.
AB  - We have reported a beneficial effect of donor vertebral body bone marrow cells
      (DBMC) infusions in cadaver renal allograft recipients in a 6-year follow-up, but
      with a transient increase in early (6 month) postoperative CMV infections and
      concomitant suppressed immunoglobulins (Ig) production. We also found that
      although there was no difference between the DBMC-infused and non-infused
      (control) groups in the development of donor-specific antibody, we now describe
      an additional difference seen in the percent reactive antibody (PRA) reactivity
      against a panel of HLA antigens that developed postoperatively. We hypothesize
      that (allogeneic) antigen presenting cells in the DBMC, systemically infused,
      caused the generation of recipient T suppressor (T4-suppressor) cells, thereby
      "inducing" a negative influence on B cell Ig production. We tested this notion in
      vitro by incubating PBL from CMV IgG positive laboratory volunteers with either
      (allogeneic) T-cell depleted DBMC or donor spleen cells (DSPC) from (the same)
      cadaver donors. After 7 days, the (responding) T cells were collected using
      magnetic beads and placed in culture with purified B cells freshly obtained from
      the same (autologous) CMV positive volunteer. To these cultures were added either
      media or 40 ng of CMV antigen. After 3, 5, 7, and 9 days, the expression of
      surface anti-CMV Ig was measured by flow cytometry using a panel of fluorescent
      markers double-labeled for activated B cells (CD20, CD19, and HLA DRw) and CMV
      FITC. We also determined the phenotype of the cultured T cells using anti-CD3,
      CD4, and CD62L specific monoclonal antibodies. B cells that had been in contact
      with autologous T cells derived from DBMC cultures (TBM) were less likely to
      express anti-CMV surface Ig than those cultured with DSPC (TSP). The flow
      cytometry analysis revealed an increase in the number of T4 suppressor cells
      (CD3+, CD4+, CD62L+) in the TBM group, whereas the T4 helper phenotype (CD3+,
      CD4+, CD62L-) predominated in the TSP group. These in vitro findings support the
      notion that (allogeneic) DBMC infusions can induce a T4 suppressor (regulatory)
      influence and thereby indirectly affect B-cell function.

PMID- 12507812
TI  - Regulatory CD8+CD28- T cells in heart transplant recipients.
AB  - Human regulatory CD8+CD28- T cells (Ts) generated in vitro were demonstrated to
      suppress the activation and proliferation of T helper cells (Th) induced by
      allogeneic cells. This effect requires cell-to-cell contact, is antigen-specific,
      and results in Th anergy. To study the population of CD8+CD28- T cells present in
      vivo, flow cytometry was performed on whole blood specimens obtained from 25
      heart transplant recipients and 12 normal controls. A significant expansion of
      CD8+CD28- T cells was found in transplant recipients as compared with normal
      individuals (p = 0.005). Expression of CD38, human leukocyte antigen-DR, and
      perforin positive cells within the CD8+CD28- subset was significantly higher in
      transplant patients than in normal controls, yet there was no correlation between
      the expression of these markers and acute rejection. Expression of the CD27
      marker, however, was significantly higher within CD8+CD28- T cells from patients
      without rejection as compared with patients in rejection (p = 0.005), indicating
      that the memory-like CD8+CD28-CD27+ T-cell subset comprises regulatory cells,
      which play a protective role for the graft. CD8+CD28- T cells isolated from
      transplant patients did not display cytotoxic activity against donor cells and
      showed high expression of the killing inhibitory receptor CD94. This study
      identifies the phenotypic changes that occur in patients with heart transplants
      and opens new avenues for the induction of specific immunosuppression in
      transplantation.

PMID- 12507813
TI  - CD28 signaling in neutrophil induces T-cell chemotactic factor(s) modulating T
      cell response.
AB  - We previously reported that human peripheral blood neutrophils express CD28 and
      interact with macrophage B7 to generate CD28 signaling through PI-3 kinase. Here,
      we demonstrate that crosslinking of CD28 on neutrophils results in the release of
      IFN-gamma, which restricts amastigote growth and modulates CD4+ T cells cytokine
      secretion. CD28 crosslinking also induces a T-cell chemotactic factor (TCF) that
      induces chemotactic migration of CD4+ T cells. Based on our previous and the
      current set of data, we propose an operational model explaining how neutrophils
      are involved in Leishmania infection and how the reported effect of neutrophils
      on the control of infection is mediated by alteration of T-cell function.

PMID- 12507814
TI  - Autoreactivity against induced or upregulated abundant self-peptides in HLA
      A*0201 following measles virus infection.
AB  - Infectious agents have been implied as causative environmental factors in the
      development of autoimmunity. However, the exact nature of their involvement
      remains unknown. We describe a possible mechanism for the activation of
      autoreactive T cells induced by measles virus (MV) infection. The display of HLA
      A*0201 associated peptides obtained from MV infected cells was compared with that
      from uninfected cells by mass spectrometry. We identified two abundant self
      peptides, IFI-6-16(74-82) and Hsp90beta(570-578), that were induced or
      upregulated, respectively, following infection. Their parental proteins, the type
      I interferon inducible protein IFI-6-16, and the beta chain of heat shock protein
      90, have not been involved in MV pathogenesis. MV infection caused minor and
      major changes in the intracellular expression patterns of these proteins,
      possibly leading to altered peptide processing. CD8+ T cells capable of
      recognizing the self-peptides in the context of HLA-A*0201 were detectable at low
      basal levels in the neonatal and adult human T cell repertoire, but were
      functionally silent. In contrast, peptide-specific producing IFN-gamma producing
      effector cells were present in MV patients during acute infection. Thus, MV
      infection induces an enhanced display of self-peptides in MHC class I, which may
      lead to the temporary activation of autoreactive T cells.

PMID- 12507815
TI  - Genetic engineering of T cell specificity for immunotherapy of cancer.
AB  - The ultimate goal of immunotherapy of cancer is to make use of the immune system
      of patients to eliminate malignant cells. Research has mainly focused on the
      generation of effective antigen specific T-cell responses because of the general
      belief that T-cell immunity is essential in controlling tumor growth and
      protection against viral infections. However, the isolation of antigen specific T
      cells for therapeutic application is a laborious task and it is often impossible
      to derive autologous tumor specific T cells to be used for adoptive
      immunotherapy. Therefore, strategies were developed to genetically transfer tumor
      specific immune receptors into patients T cells. To this end, chimeric receptors
      were constructed that comprise antibody fragments specific for tumor associated
      antigens, linked to genes encoding signaling domains of the T-cell receptor (TCR)
      or Fc receptor. T cells expressing such chimeric antibody receptors recapitulate
      the immune specific responses mediated by the introduced receptor. Recently, we
      introduced chimeric TCR genes into primary human T lymphocytes and demonstrated
      that these T cell transductants acquired the exquisite major histocompatibility
      complex (MHC) restricted tumor specificity dictated by the introduced TCR.
      Importantly, the introduction of chimeric TCR bypasses problems associated with
      the introduction of nonmodified TCR genes, such as pairing of introduced TCR
      chains with endogenous TCR chains and unstable TCRalpha expression. A novel
      strategy which is completely independent of available tumor specific T-cell
      clones for cloning of the TCR genes was recently used to transfer MHC restricted
      tumor specificity to T cells. Human "TCR-like" Fab fragments obtained by in vitro
      selection of Fab phages on soluble peptide/MHC complexes were functionally
      expressed on human T lymphocytes, resulting in MHC restricted, tumor specific
      lysis and cytokine production. In addition, affinity maturation of the antibody
      fragment on Fab phages allows improvement of the tumor cell killing capacity of
      chimeric Fab receptor engrafted T cells. Developments in retroviral transfer
      technology now enables the generation of large numbers of antigen specific T
      cells that can be used for adoptive transfer to cancer patients. In this article
      we summarize the developments in adoptive T cell immunogenetic therapy and
      discuss the limitations and perspectives to improve this technology toward
      clinical application.

PMID- 12507816
TI  - Diversity and somatic hypermutation of the Ig VHDJH, V kappa J kappa, and V
      lambda J lambda gene segments in lymphoma B cells: relevance to the origin of the
      neoplastic B cell clone.
AB  - Burkitt's lymphoma (BL) is a malignancy of B cells characterized by chromosomal
      translocations involving the immunoglobulin (Ig) and c-MYC gene loci. To address
      the putative role of antigen in the clonal expansion of these neoplastic B cells,
      we analyzed the VHDJH and VLJL gene segments expressed by the established cell
      lines derived from six endemic BL and six sporadic BL. Eight BL cell lines used
      genes of the VH3 family, two of the VH4, and two of the VH1. Eight VL chains were
      kappa (four members of the V kappa3, two of the V kappa1, and two of the V kappa2
      subgroups) and four lambda (three members of the V lambda1 and one of the Vl
      ambda3 subgroup). The VH gene utilization was stochastic (i.e., it reflected the
      relative representation of the different VH gene family members in the human
      haploid genome). In contrast, the VL gene utilization was skewed toward the
      overutilization of the V kappa3 and V lambda1 gene subgroups. When compared with
      those of the respective germline genes, the sequences of the expressed Ig VDJ
      genes displayed nucleotide differences that resulted from somatic hypermutation.
      In three endemic and three sporadic BL cells, nucleotide changes yielding amino
      acid substitutions segregated within the complementarity determining region,
      indicating the application of a positive pressure for replacement mutations and
      suggesting that these neoplastic lymphocytes underwent a process of clonal
      selection driven by antigen, perhaps emerging from or transitioning through
      germinal centers.

PMID- 12507817
TI  - Requirement of caspase-3 for efficient apoptosis induction and caspase-7
      activation but not viral replication or cell rounding in cells infected with
      vesicular stomatitis virus.
AB  - Infection with vesicular stomatitis virus (VSV), a rhabdovirus and economically
      significant animal pathogen, was previously demonstrated to induce apoptosis. The
      mechanism of induction and the role of apoptosis in the VSV-host response have
      not been completely elucidated. Previous data from our laboratory have suggested
      that caspase-3 is required for the induction of apoptosis but not viral
      replication in VSV-infected cells. However, these studies used inhibitors that
      are selective but not specific for caspase-3. To circumvent this difficulty, we
      infected both MCF-7 cells which do not express caspases-3 (null), and stable
      transfectants which express caspase-3 (C3+). When caspase-3 null cells were
      infected, significant PARP cleavage did not occur, but when C3+ cells were
      infected, PARP cleavage did occur efficiently. Studies in null and C3+ also
      suggest that: (1) caspases-3 and -7 are activated sequentially after VSV
      infection; (2) cell shrinkage and detachment are caspase-3 dependent, but cell
      rounding is not; and (3) the viral titers were similar between caspase-3 null and
      C3+ cells suggesting that activation of caspases-3 and -7 are not required for
      viral replication. Taken together, these results strongly support that the
      activation of caspase-3 by VSV infection is required for efficient apoptosis
      induction but not viral replication in vitro. Apoptosis mediated by caspase-3,
      then, is likely either a host cell response to viral replication or perhaps may
      be required for in vivo viral replication and spread.

PMID- 12507818
TI  - Cytokine gene polymorphisms moderate responses to respiratory syncytial virus in
      adults.
AB  - Immune responses and illness severity during viral upper respiratory infections
      may be influenced by the local elaboration of cytokines. Cytokine gene
      polymorphisms moderate immune responses and severity of illness in various
      inflammatory and infectious diseases. We performed cytokine genotyping on 29
      adults experimentally inoculated with respiratory syncytial virus (RSV) to
      determine whether specific cytokine gene polymorphisms are associated with immune
      responses or illness severity. DNA was extracted from leukocytes and assayed for
      TNF-alpha, IFN-gamma, IL-6, IL-10 and TGF-beta1 genotypes using polymerase chain
      reaction-sequence-specific primer technology. Outcomes consisted of baseline and
      convalescent RSV-specific serum IgG and nasal IgA titers, nasal secretion
      weights, nasal, throat and general symptom scores, and nasal cytokine protein
      levels. IFN-gamma genotype was directly related with the frequency of subjects
      having at least a four-fold increase in RSV-specific serum IgG and TNF-alpha
      genotype was inversely associated with the frequency of subjects having at least
      a twofold increase in RSV-specific nasal IgA. Additionally, IL-6 genotype was
      predictive of certain measures of illness expression, while IFN-gamma genotype
      predicted IL-1 protein levels, and TNF-alpha genotype predicted IL-6 and IL-8
      protein levels in nasal lavage fluids. There were no associations between IL-10
      or TGF-beta1 and any of the outcome parameters. These results suggest that
      certain cytokine gene polymorphisms moderate immune responses and illness
      severity in adults experimentally exposed to RSV.

PMID- 12507819
TI  - MHC class II genes in HCV viral clearance of hepatitis C infected Hispanic
      patients.
AB  - The frequency of class II human leukocyte antigen (HLA) alleles in 112 infected
      patients of Hispanic ancestry with serology positive for hepatitis C virus (HCV)
      was investigated. Our studies failed to demonstrate significant association
      between class II HLA alleles and the outcome of HCV infection: chronic viremia
      versus spontaneous viral clearance. Our results suggest that the genes
      responsible for the outcome are unknown, so far, and those HLA associations
      reported in several ethnic groups may represent genetic markers in nonrandom
      association with the responsible genes involved in determining viral clearance or
      chronic viremia following HCV infection.

PMID- 12507820
TI  - The association of class I HLA alleles and antibody levels after a single dose of
      measles vaccine.
AB  - Despite the success of the current measles vaccine in controlling disease in
      industrialized countries, the importance of vaccine failure has become
      increasingly apparent. Our objective was to determine if associations exist
      between seronegativity after measles vaccination and class I human leukocyte
      antigen (HLA) alleles. We undertook a cross-sectional observational study in
      Rochester, Minnesota, with 242 school-age children previously recruited from a
      communitywide seroprevalence study. We studied two groups of subjects: 72 were
      seronegative (EIA < or =0.8 after a single dose of measles vaccine) and 170 were
      seropositive (enzyme immunoassy [EIA] > or =1.0 after one dose). We used the
      resources of Mayo Clinic's tissue typing laboratory for serotyping class I HLA-A
      and HLA-B alleles via microlymphocytotoxicity assays. We found no statistically
      significant associations with class I HLA-A but did find associations with class
      I HLA-B, which includes alleles associated with seronegativity (B8, B13, and B44)
      and those associated with seropositivity (B7 and B51). Elucidation of the
      specific peptide-HLA complex interactions that lead to varying or failed immune
      responses may provide fertile groundwork for improved vaccines that can overcome
      limitations of the current live, attenuated measles vaccine.

PMID- 12507821
TI  - Protective effect of DRB1 locus against type 2 diabetes mellitus in Mexican
      Mestizos.
AB  - The aim of the study was to investigate the participation of human leukocyte
      antigen (HLA) class II alleles in the expression of type 2 diabetic and in
      nondiabetic subjects with and without family history of diabetes. The purpose was
      to evaluate any HLA association and to look for different patterns of insulin
      resistance and insulin secretion, comparing subjects with a low probability of
      developing diabetes, as a result of their family history. We recruited 87 healthy
      subjects without family history of diabetes, 48 healthy subjects with family
      history, and 47 type 2 diabetic patients. All of them were Mexican Mestizos of
      central Mexico. Using a standard 75-g oral glucose tolerance test, insulin
      resistance was determined and insulin secretion was assessed with the HOMA model.
      DRB1, DQA1 and DQB1 alleles were typed using polymerase chain reaction-sequence
      specific oligonucleotide probe (PCR-SSOP) and sequence specific primers (PCR
      SSP). Nondiabetic subjects had similar HOMA-IR and DeltaI 30/DeltaG 30 index
      (HOMA). A significant decreased frequency of DRB1*0403 (p = 0.01; odds ratio [OR]
      = 0.20) was demonstrated in type 2 diabetic patients, and DRB1*0701 (p = 0.02; OR
      = 0.17) in nondiabetics with family history of diabetes. These alleles associated
      with protection against type 2 diabetes, share glutamic acid at position-74 and
      were previously demonstrated to contribute to protection against type I diabetes.

PMID- 12507822
TI  - Clinical and genetic heterogeneity in Mexican patients with ulcerative colitis.
AB  - Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology.
      Genetic factors implied on its onset and severity may include genes located
      within the class II major histocompatibility complex (MHC) region. The aim of
      this study was to determine the relationship between human leukocyte antigen
      (HLA)-DRB1 alleles with the clinical disease patterns of UC in Mexican Mestizo
      patients. High-resolution HLA typing was performed by polymerase chain reaction
      sequence specific oligonucleotide (PCR)-SSO reverse dot blot and PCR-single
      strand polymorphism in 67 patients with UC and 99 ethnically matched healthy
      controls. UC patients overall showed an increased frequency of HLA-DR1 as
      compared with healthy controls (17.1% versus 5%, [pC = 0.003, OR = 3.9]).
      Patients with extensive colitis showed increased frequencies of HLA-DR1 (pC = 1 x
      10(-10), OR = 13.9), HLA-DRB1*0103 (pC = 1 x 10(-3), OR = 21.7), HLA-DRB1*0102
      (pC = 0.007, OR = undetermined), and HLA-DR15 (pC = 1 x 10(-3), OR = 8.5) when
      compared with healthy controls. We also found a statistically increased frequency
      of HLA-DR15 in UC patients with extensive colitis compared with UC patients with
      only distal colitis (18.7% versus 1.8%, pC = 0.03; OR = 12.2). When patients who
      underwent proctocolectomy were compared with those who did not, an increased
      frequency of HLA-DRB1*0103 was observed (21.8% versus 4.9%; pC = 0.03; OR = 5.4;
      95% confidence interval, 1.39-21.93). Also, patients with proctocolectomy showed
      increased frequencies of HLA-DR1 (pC = 1 x 10(-3), OR = 24.2) and HLA-DRB1*0103
      (pC = 1 x 10(-3), OR = 50.6) when compared with healthy controls. We concluded
      that HLA-DR1 is associated with genetic susceptibility to UC in the Mexican
      Mestizo population. HLA-DR15 distinguishes a subgroup of patients with extensive
      colitis and the HLA-DRB1*0103 allele distinguishes a subgroup of severe form of
      disease that might require surgical management.

PMID- 12507823
TI  - Allelic distribution of human leukocyte antigen in Iranian patients with
      pulmonary tuberculosis.
AB  - There is convincing evidence for a genetic component in susceptibility to
      tuberculosis (TB) in humans. Attempts to link susceptibility to TB to human
      leukocyte antigen (HLA) phenotype have produced conflicting data. The purpose of
      this study was to determine whether HLA phenotype is associated with clinical TB.
      We compared the frequencies of HLA alleles in 44 Iranian sputum smear positive
      pulmonary TB patients with allele frequencies of 108 healthy adults. HLA typing
      was performed by lymphocytotoxicity assay. The frequencies of HLA-B17 and -DR14
      were higher in TB patients and the frequencies of HLA-A26 and -B27 were higher in
      healthy controls (p value < 0.05, corrected p value [pc] >0.05). Our findings
      suggest that these alleles are associated (either positively or negatively) with
      pulmonary TB in an Iranian population. However, considering corrected p value,
      our data are not conclusive and should be considered preliminary.

PMID- 12507824
TI  - Study of MICA alleles in 201 African Americans by multiplexed single nucleotide
      extension (MSNE) typing.
AB  - We have developed a method for major histocompatibility complex class I chain
      related gene A (MICA) genotyping using multiplexed single nucleotide extension
      (MSNE) and flow cytometric analysis of an array of fluorescent microspheres. This
      technique employs a polymerase chain reaction-derived target DNA containing all
      the polymorphic sites of MICA, synthetic complementary primers, biotinylated
      dideoxynucleotide triphosphate, fluorescent reporter molecules (streptavidin
      phycoerythrin), and thermophilic DNA polymerase. Genomic DNA was amplified by
      MICA locus-specific primers and the MSNE reactions were carried out in the
      presence of 30 MSNE primers used to assay polymorphisms in exons 2, 3, and 4 of
      the MICA genes. Thirty-two previously typed cell lines were used as reference
      material. The MICA gene frequencies among 201 African-American unrelated donors
      were determined. Of 51 previously known alleles, 18 were observed in African
      Americans, compared to 16 that were found in North American Caucasians and 9 in
      South American Indians, suggesting a more diversified allelic distribution in
      African-Americans. MICA*00201 and MICA*00801 were the two most frequent alleles
      in African-Americans. We observed a high degree of linkage disequilibrium between
      certain alleles of MICA and of human leukocyte antigen-B in the African-American
      population. The methodology described here offers a powerful new approach to DNA
      typing of the MICA alleles.

PMID- 12507825
TI  - Gene and haplotype frequencies for the loci hLA-A, hLA-B, and hLA-DR based on
      over 13,000 german blood donors.
AB  - Numerous applications in clinical medicine and forensic sciences depend on
      reliable data concerning the frequencies of human leukocyte antigen (HLA) genes
      and haplotypes. Assuming a Hardy-Weinberg equilibrium of the underlying
      population, these frequencies can be estimated from phenotype data using an
      expectation-maximization-algorithm also known under the name "gene counting." We
      have refined this algorithm in order to cope with the heterogeneous resolution of
      HLA phenotypes frequently occurring in large datasets due to the structure of the
      HLA nomenclature. This was a prerequisite to analyze a set of 13,386 blood donors
      contributed by over 40 blood banks who were tested for HLA-DR when they
      volunteered to become marrow donors. This data set is still unique in the German
      national donor registry because their HLA-DR-typing was not biased by patient
      oriented searches or other strategies for selective typing. As a consequence of
      the size of the sample, the frequency estimates for the genes and the two- and
      three-locus haplotypes of HLA-A, HLA-B, and HLA-DR are of unprecedented precision
      and allow interesting projections concerning the efficiency and economic aspects
      of the development of a large donor registry in Germany.

PMID- 12507826
TI  - Prevalence and HLA association of GAD65 antibodies in Hungarian schoolchildren.
AB  - Pancreas beta-cell autoantibodies are important tools in prediction of type 1
      diabetes, however, background frequencies of these markers reveal considerable
      population-specific variations. The aim of current study was to determine the
      frequency of glutamic acid decarboxylase (65kD) antibodies (GADA) in healthy
      Hungarian schoolchildren (n = 2,664) and to correlate development of GADA with
      HLA DQ genotypes. GADA was determined using a radioligand assay (cut-off limit:
      97.5th percentile); HLA DQ genotypes were identified with allele-specific
      polymerase chain reaction. Thirty-five children (1.3%) tested positive for GADA
      among which the proportion of girls was significantly higher when compared with
      boys (1.8% and 0.8%, p = 0.03). The study population was followed for 5.2 years
      and one girl in the whole cohort, who tested positive for GADA, has developed
      diabetes. HLA DQ2/DQ8 and DQ2/y genotypes (where y not equal DQB1*0302, *0301,
      *0602, *0603) were significantly more prevalent in the GADA positive group than
      in antibody negative children (17.1% vs 1.7%, p = 0.0003 and 25.7% vs 10.3%, p =
      0.027, respectively). In conclusion, the prevalence of GADA in the Hungarian
      general population is in the middle of the range found in other Caucasian ethnic
      groups. Individuals carrying HLA DR3-DQ2 haplotype and females were more prone to
      develop GADA. We suggest that for future screening programs it is important to
      determine predictive value of islet-cell antibodies in populations with varying
      disease incidence.

PMID- 12507827
TI  - Polymorphisms of human TAP2 detected by denaturing gradient gel electrophoresis.
AB  - The human transporter associated with antigen processing (TAP1 and TAP2) genes
      are located in the human leukocyte antigen (HLA) class II region of the genome
      and encode proteins that form a heterodimer essential for the transport of
      endogenous peptides into the endoplasmic reticulum for assembly with HLA class I
      molecules. Type 1 diabetes is an autoimmune disease that is associated with the
      HLA region of the genome, with HLA class II genes conferring the greatest
      statistical risk. The presentation of self-peptides by HLA class I molecules is
      defective in individuals with this disease, and both TAP1 and TAP2 are potential
      contributors to this defect. Denaturing gradient gel electrophoresis (DGGE) was
      applied to screen all 11 exons and the 3' flanking region of TAP2 for
      polymorphisms in individuals with type 1 diabetes patients and controls. Seventy
      polymorphisms, including 51 in introns, 4 in the 3' flanking region, and 15 in
      exons, were identified. Sequencing of polymorphic DNA fragments revealed several
      new polymorphisms, including a Gln --> Arg substitution at codon 611 and a GT -->
      GC polymorphism affecting the donor splice site of intron 4, that might be of
      functional significance. None of the polymorphisms examined differed in frequency
      between individuals with type 1 diabetes and controls.

PMID- 12507828
TI  - Detection of HLA polymorphisms by ligase detection reaction and a universal array
      format: a pilot study for low resolution genotyping.
AB  - We present our results in the identification of polymorphic sites within the
      second exon of the human leukocyte antigen A (HLA-A) region using the DNA
      microarray technology. Allele specific detection was performed by polymerase
      chain reaction followed by ligase detection reaction (LDR) in combination with a
      universal array, a powerful method for high throughput DNA sequence analysis. By
      this approach we confirmed 32 human samples previously characterized by direct
      DNA sequencing, thus demonstrating the interest of this approach.

PMID- 12507829
TI  - Nomenclature for factors of the HLA system, updated July 2002.

PMID- 12507830
TI  - Nomenclature for factors of the HLA system, updated August 2002.

PMID- 12507831
TI  - Sustained activity and spectrum of selected extended-spectrum beta-lactams
      (carbapenems and cefepime) against Enterobacter spp. and ESBL-producing
      Klebsiella spp.: report from the SENTRY antimicrobial surveillance program (USA,
      1997-2000).
AB  - Enterobacter spp. and Klebsiella spp. are important clinical pathogens that
      frequently exhibit resistance to third-generation cephalosporins. In Enterobacter
      spp. strains, resistance is usually due to derepression of the Amp C locus,
      whereas plasmid-encoded extended-spectrum beta-lactamases (ESBLs) are primarily
      responsible for resistance in Klebsiella spp. Here we report the results from the
      SENTRY Antimicrobial Surveillance Program concerning the rates and trends of
      resistance to extended-spectrum beta-lactams and other antimicrobial agents in
      Enterobacter spp. and Klebsiella spp. isolated between 1997 and 2000 in
      participating hospitals in the United States. Among Enterobacter spp., resistance
      (MIC>or=32 mg/l) to aztreonam, ceftazidime and ceftriaxone ranged from 12.3 to
      21.2% over the 4 years, whereas resistance in Klebsiella (MIC>or=2 mg/l) ranged
      from 5.9 to 6.8%. There was no trend toward increased resistance to these beta
      lactam agents over the monitored period. Carbapenems (imipenem, meropenem) and
      cefepime had excellent activity against both ceftazidime-susceptible and 
      resistant Enterobacter spp. and Klebsiella spp. (>99% susceptible), although the
      minimum inhibitory concentration values of cefepime were higher in ceftazidime
      resistant isolates compared with ceftazidime-susceptible isolates. Co-resistance
      to other antimicrobial agents was common in both tested genus groups.

PMID- 12507832
TI  - In vitro activity of beta-lactams in combination with other antimicrobial agents
      against resistant strains of Pseudomonas aeruginosa.
AB  - Using the chequerboard titration method, the activity in combination of beta
      lactams, fluoroquinolones and aminoglycosides was investigated against 24
      Pseudomonas aeruginosa isolates resistant to these antibiotics. Synergy was
      detected with one or more antimicrobial combinations against 15 of 24 (63%)
      isolates and partial synergy was detected with one or more combinations against
      all 24 isolates. No antagonism was seen with any combination. Ceftazidime and
      cefepime with aztreonam, amikacin and isepamicin showed synergy or partial
      synergy against 12-20 (50-80%) isolates. Imipenem and meropenem with amikacin and
      isepamicin showed synergy or partial synergy against eight to 12 (33-50%)
      isolates. The results of this study indicate that against P. aeruginosa, synergy
      may occur between beta-lactams, fluoroquinolones and aminoglycosides although the
      strains are resistant to the individual antibiotics.

PMID- 12507833
TI  - The increased bactericidal activity of a fatty acid-modified synthetic
      antimicrobial peptide of human cathepsin G correlates with its enhanced capacity
      to interact with model membranes.
AB  - The bactericidal potency of a synthetic peptide (CG 117-136) of human lysosomal
      cathepsin G (cat G) can be substantially increased by covalent attachment to its
      N- or C-termini, of saturated, linear fatty acids (FAs), namely those with C-8, C
      10 and C-12 hydrocarbon chains. In order to understand better the mechanism by
      which FA moieties increase the bactericidal activity of CG 117-136, the
      interaction of N-terminally FA-modified peptides with artificial membranes was
      studied. First, the content of secondary structure motifs in the modified and
      unmodified peptides was determined by circular dichroism (CD). A marked increase
      in the propensity of FA-modified CG 117-136 to form an alpha-helix structure was
      observed for the C-8, C-10 and C-12 derivatives compared with unmodified/short
      chain and long-chain (C-14, C-16, C-18) derivatives. These effects were observed
      both in the presence of large unilamellar liposomes or in trifuluoroethanol, a
      membrane-stimulating agent. Second, the capacity of peptides to insert into large
      unilamellar liposomes as a function of FA length was determined by their ability
      to release a trapped fluorescent dye. FA derivatives with the highest alpha
      helical content were found to be the most effective in releasing a fluorescent
      dye, compared with an unmodified peptide and/or derivatives having a low alpha
      helical content. The ability of the peptides to attain alpha-helical structure in
      the membrane-like environment and the ability to disrupt the liposomal membrane,
      therefore correlate remarkably well with their increased ability to kill
      bacteria. A plausible explanation for improved bactericidal action of the
      modified peptide is that the FA moiety facilitates formation of the peptide with
      an alpha-helical structure formation in membranes, which is essential for
      disrupting the integrity of the bacterial cytoplasmic membrane.

PMID- 12507834
TI  - Antimicrobial properties of highly fluorinated bis-ammonium salts.
AB  - Four series of new highly fluorinated bisammoniums (Quaterfluo Tx, Quaterfluo Bx,
      Quaterfluo Cx, Quaterfluo Dx) were tested to evaluate their anti-bacterial and
      anti-fungal properties. Four microbial strains were used to perform the study:
      Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus
      niger. The antimicrobial efficacy was measured by bacterial and fungal growth
      inhibition expressed as minimal inhibitory concentration (MIC) values. The
      Quaterfluo Tx series had very good antimicrobial activity, particularly against
      Gram-negative bacteria. A speed of kill test carried out with Quaterfluo T3
      showed bactericidal activity. The introduction of perfluorinated chains into the
      quaternary ammonium surfactant structure leads to particularly active
      antimicrobial agents which not only have bacteriostatic properties but which
      could be also powerful bactericides.

PMID- 12507835
TI  - In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the
      causative agent of Chagas disease.
AB  - Ravuconazole is an experimental triazole derivative with potent and broad
      spectrum antifungal activity and a remarkably long half-life in humans. In this
      work, we investigated the in vitro and in vivo activities of this compound
      against Trypanosoma cruzi. Ravuconazole showed very potent in vitro anti-T. cruzi
      activity with minimal inhibitory concentrations (MIC) of 300 and 1 nM against the
      extracellular epimastigote and intracellular amastigote forms, respectively. As
      with other azole derivatives, ravuconazole at the MIC led to an essentially
      complete depletion of the epimastigotes' endogenous C4,14-desmethyl sterols and
      their replacement by di- and tri-methylated sterols. In murine acute models of
      acute Chagas disease, it was found that ravuconazole treatment led to high levels
      of parasitological cures, but only when given twice a day (b.i.d.), consistent
      with its short terminal half-life in mice (4 h). Furthermore, it was found that
      this curative activity was restricted towards nitrofuran/nitroimidazole
      susceptible (CL) and partially drug-resistant (Y) strains of T. cruzi, with no
      curative activity in animals infected with the fully drug-resistant Colombiana
      strain. No curative activity occurred in a chronic model of the disease. No toxic
      side effects were observed resulting from treatment with the triazole.
      Ravuconazole is a very potent and specific anti-T. cruzi agent in vitro but its
      in vivo activity in mice is limited, probably due to its unfavourable
      pharmacokinetic properties in this animal model. However, these results do not
      necessarily rule out the potential utility of ravuconazole in the treatment of
      human T. cruzi infections.

PMID- 12507836
TI  - Parasitological cure of acute and chronic experimental Chagas disease using the
      long-acting experimental triazole TAK-187. Activity against drug-resistant
      Trypanosoma cruzi strains.
AB  - We investigated the activity of TAK-187, an experimental antifungal triazole with
      a long terminal half-life in several experimental animals, against Trypanosoma
      cruzi. In vitro studies showed that the minimal inhibitory concentration (MIC)
      against the (extracellular) epimastigote form was 0.3-1 microM, while the
      corresponding concentration against clinically relevant intracellular amastigotes
      was 1 nM. At the MIC the endogenous epimastigote C4,14-desmethyl sterols were
      replaced by di- and tri-methylated sterols, supporting the notion that the
      primary target of TAK-187 is the parasite's sterol C14alpha demethylase. We
      investigated the in vivo activity of the compound in a murine model of acute
      Chagas disease, using T. cruzi strains with different susceptibilities to the
      drugs currently used clinically (nitrofurans and nitroimidazoles). It was found
      that TAK-187 given orally at 20 mg/kg induced complete protection against death
      and high levels (60-100%) of parasitological cures, independently of the
      infecting strain and even when administered every other day (e.o.d.), consistent
      with its long terminal half-life in mice. Other experiments, using longer
      treatment periods were carried out in both acute and chronic models of the
      disease and showed that TAK-187 given at 10-20 mg/kg e.o.d. induced 80-100%
      survival with 80-100% of parasitological cures of survivors in both models. No
      toxic side effects were observed in any of the experimental protocols. TAK-187 is
      a potent anti-T. cruzi compound with trypanocidal activity in vivo and should be
      considered for further studies as a potential specific treatment of human Chagas
      disease.

PMID- 12507837
TI  - Results of a prospective, randomized, double blind comparison of the efficacy and
      the safety of sequential ciprofloxacin (intravenous/oral)+metronidazole
      (intravenous/oral) with ceftriaxone (intravenous)+metronidazole
      (intravenous/oral) for the treatment of intra-abdominal infections.
AB  - The efficacy and the safety of sequential intravenous/oral (i.v./p.o.)
      ciprofloxacin (CIPX) plus i.v./p.o. metronidazole (MTR) was compared with i.v.
      ceftriaxone (CTRX) plus i.v./p.o. MTR in the treatment of complicated intra
      abdominal infections. One hundred and forty two patients received study
      medications. Of these, 135 could be studied. Sixty-nine patients were randomized
      in the CIPX arm of the study and 66 in the CTRX arm. In the CIPX group 58
      patients were switched to oral treatment and 11 patients remained in the
      intravenous arm. In the CTRX group 57 patients switched to oral MTR continuing
      i.v. CTRX and 9 patients remained in the i.v. branch. Success rates at the end of
      treatment in patients who switched to oral were 100% in both the CIPX group and
      the CTRX group. For validated patients continuing on oral, the success rates at
      the end of treatment were 63.6 and 33.3% in the CIPX and CTRX groups
      respectively. Overall success rates at the end of treatment and follow-up in all
      patients were 94.2% in the CIPX group and 89.4% in the CTRX group. Overall
      success rates at the end of treatment in patients with proven bacterial infection
      were 92.9% in the CIPX group and 88.3% in the CTRX group. Duration of
      hospitalization (days) for studied patients was 22.7+/-8.2 in the CIPX and 19.6+/
      14.5 in the CTRX group. There was no statistical difference between the CIPX and
      CTRX groups in both the intent to treat and in the modified intent to treat
      populations. Conversion to oral therapy with CIPX/MTR was as effective as
      continued intravenous therapy with CTRX and oral MTR in those patients able to
      tolerate oral feeding.

PMID- 12507838
TI  - Severe nosocomial infections with imipenem-resistant Acinetobacter baumannii
      treated with ampicillin/sulbactam.
AB  - Forty consecutive patients with nosomial infections caused by multidrug-resistant
      Acinetobacter baumannii were treated with intravenous ampicillin/sulbactam. The
      infections were primary bloodstream (32.5%), pneumonia (30%), urinary tract
      (15%), peritonitis (7.5%), surgical site (7.5%), meningitis (5%) and sinusitis
      (2.5%). Most were severe infections with underlying conditions (median APACHE II
      score: 14.5) and 72.5% occurred in the ICU. Twenty-seven (67.5%) were
      improved/cured, seven (17.5%) were failures and six (15%) were considered to have
      an indeterminate outcome because patients died within the first 48 h of
      treatment. Two cases of meningitis were treated and did not respond. The median
      daily dose of ampicillin/sulbactam was 6 g/3 g and six patients received 12 g/6
      g. No adverse effects were observed. This study indicates that
      ampicillin/sulbactam may be a good and safe therapeutic option to treat severe
      nosocomial infections caused by multi-drug resistant A. baumannii.

PMID- 12507839
TI  - Rational antibiotic use and academic staff.
AB  - This study was devised to determine the knowledge, attitude and behaviour of an
      educated group of people towards antibiotic use and self-medication with
      antibiotics. Of 1380 members of academic staff (excluding those from the Faculty
      of Medicine) of Ege University, 602 were chosen by systematic sampling methods.
      Two groups were formed. Group A included academic staff from the Faculties of
      Dentistry and Pharmacy and Group B, members of all other faculties. The mean age
      was 37.4+/-11.0 and 47.0% were females. The mean antibiotic knowledge score was
      7.16+/-3.32. Self-medication with antibiotics was admitted by 45.8% of the total
      samle and 15.6% of the respondents used antibiotics until their symptoms
      disappeared regardless of the period of prescription. In Group A 48.8% and in
      Group B 80.7% of the respondents believed that antibiotics could be used for
      common cold. It is concluded that priority should be given to knowledge-based
      behaviour education programmes for the more highly educated community; there must
      also be restriction on the sale of antibiotics without prescription.

PMID- 12507840
TI  - Clinical isolates of macrolide-resistant Streptococcus pyogenes in Central
      Greece.
AB  - A total of 300 Streptococcus pyogenes isolates, collected during 2001 from five
      hospitals in the Thessalia district (Central Greece), were examined for their
      resistance to macrolides. Resistance to erythromycin was detected in 58 isolates
      (19.3%). Of these, 68.9% were susceptible to clindamycin (M-phenotype) and
      carried the mefA gene. Of the remaining isolates, 18 expressed the MLS(B)
      phenotype: 12 and six exhibited inducible and constitutive resistance to
      clindamycin, respectively. All of these strains were found to be ermA(TR)
      positive, except for four that had the ermB gene. Of the erythromycin-resistant
      strains, none was found to be resistant to penicillin, tetracycline or
      quinupristin-dalfopristin. Molecular typing by PFGE showed the presence of a
      limited number of clones.

PMID- 12507841
TI  - Lysis of methicillin-resistant Staphylococcus aureus by 2,4
      diacetylphloroglucinol produced by Pseudomonas sp. AMSN isolated from a marine
      alga.
AB  - Previously 2,4-diacetylphloroglucinol (DAPG) produced by Pseudomonas sp. AMSN
      isolated from a marine alga, had demonstrated a high level of anti-methicillin
      resistant Staphylococcus aureus (MRSA) comparable with that of vancomycin. In
      this study, this substance had bacteriolytic activity against MRSA at 1 microg/ml
      as well as similar activity against Vibrio parahaemolyticus at 24 microg/ml that
      suggests a novel antibacterial mode of action by this substance. Heat and pH
      stability tests showed it to be stable at temperatures ranging from 35 to 70
      degrees C and at pHs ranging from 2-7. It was not acutely toxic to mice at levels
      up to 100 mg/kg.

PMID- 12507842
TI  - Antimicrobial activity of magainin analogues against anaerobic oral pathogens.
AB  - Magainins are a family of potent antimicrobial cationic peptides that possess
      antimicrobial activity against a wide range of target organisms. In this study,
      the antimicrobial activity of synthetic magainin-mimetic compounds MSI-751 and
      MSI-774 was investigated against the periodontal pathogens Porphyromonas
      gingivalis, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans,
      Eikenella corrodens, Prevotella loescheii and Prevotella intermedia. P.
      gingivalis was more susceptible to MSI-751 than to MSI-774, whereas the other
      oral pathogens showed little difference in susceptibility to the two compounds.
      MSI-751 exhibited a rapid, dose-dependent bactericidal effect on P. gingivalis.
      Electron microscopy of MSI-751-treated P. gingivalis revealed intact cell wall
      vesicles devoid of cell contents, suggesting perturbation of the cytoplasmic
      membrane by this compound, perhaps equivalent to formation of membrane-disruptive
      ion channels by magainin peptides. These studies demonstrate that synthetic
      magainin derivatives exhibit antimicrobial activity against oral pathogens by
      disruption of cell membrane integrity.

PMID- 12507843
TI  - Antimicrobial resistance in Escherichia coli causing urinary tract infections in
      Costa Rica: a clinical dilemma.

PMID- 12507844
TI  - TOLL-like receptors linking innate and adaptive immune response.
AB  - Invading pathogens are controlled by the innate and adaptive arms of the immune
      system. Adaptive immunity, which is mediated by B and T lymphocytes, recognises
      pathogens by rearranged high affinity receptors. However, the establishment of
      adaptive immunity is often not rapid enough to eradicate microorganisms as it
      involves cell proliferation, gene activation and protein synthesis. More rapid
      defense mechanisms are provided by innate immunity, which recognises invading
      pathogens by germ-line-encoded pattern recognition receptors (PRR). Recent
      evidence shows that this recognition can mainly be attributed to the family of
      TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns
      (PAMP) to TLR induces the production of reactive oxygen and nitrogen
      intermediates (ROI and RNI), pro-inflammatory cytokines, and up-regulates
      expression of co-stimulatory molecules, subsequently initiating the adaptive
      immunity. In this review, we will summarize the discovery and the critical roles
      of the TLR family in host defense, briefly allude to signaling mechanisms
      mediating the response to TLR ligands, and will provide an update on current
      knowledge regarding the ligand specificity of these receptors and their role in
      immunity of domestic animals, particularly cattle.

PMID- 12507845
TI  - Western blot analysis of Leishmania infantum antigens using sera from pentamidine
      treated dogs.
AB  - Pentamidine treatment has been used successfully to establish immune cellular
      responses in recovered dogs. In this paper, we examined the appearance and
      disappearance of antibodies over time against crude Leishmania antigens and
      purified gp63 or gp70 proteins in sera from cured dogs using a Western blotting
      technique. Following the treatment, a pattern of antibody specificities to
      parasite antigens was observed in the sera of cured dogs. Antibodies to gp63 and
      gp70 were maintained after cure. In addition, the reaction with a 26 kD band
      observed during the clinical phase was no longer recognized by sera taken from
      recovery dogs. Interestingly, two proteins, 85 and 110 kD, not observed during
      the patent phase were detected by sera taken from treated dogs. Such patterns of
      antibody specificities to various parasite antigens might represent a useful
      parameter to determine the actual phase of the disease process.

PMID- 12507846
TI  - Ginseng extract in aluminium hydroxide adjuvanted vaccines improves the antibody
      response of pigs to porcine parvovirus and Erysipelothrix rhusiopathiae.
AB  - Ginseng, the dry extract prepared from the Panax ginseng C.A. Mayer-root contain
      immunomodulators named ginsenosides, which in the pig enhance the antibody
      response to viral and bacterial antigens. The enhancing effect of ginseng was
      demonstrated vaccinating pigs against porcine parvovirus (PPV) and Erysipelothrix
      rhusiopathiae infections, using commercially available vaccines. The potency of
      the licensed, aluminium hydroxide adjuvanted; vaccines were compared with those
      supplemented with ginseng. The antibody response to PPV was measured by the
      haemagglutination inhibition (HI) test whereas the mouse potency test and ELISA
      evaluated the immune response to E. rhusiopathiae. Antibodies to the 64-66 kDa
      glycoprotein of the E. rhusiopathiae were demonstrated by immunoblotting. The
      qualitative antibody responses were evaluated by means of ELISA(s) using
      monoclonal antibodies to swine IgG1 and IgG2. The addition of 2mg ginseng per
      vaccine dose, potentiate the antibody response of the commercial vaccines without
      altering their safety. Significantly higher (P<0.001) antibody titres were
      achieved to both PPV and to E. rhusiopathiae by the supplementation with ginseng.
      Aluminium hydroxide adjuvanted vaccines favoured the production of IgG1
      antibodies. Interestingly, the vaccines supplemented with ginseng favoured IgG2.
      The vaccines used in the evaluations varied in their immunogenic potency.
      However, after the addition of ginseng the less immunogenic vaccine proved to be
      as potent as the better one without ginseng. Thus, the use of ginseng as a co
      adjuvant provides a simple, safe and cheap alternative for improving the potency
      of aluminium hydroxide adjuvanted vaccines.

PMID- 12507847
TI  - Adjuvant effect of ginseng extracts on the immune responses to immunisation
      against Staphylococcus aureus in dairy cattle.
AB  - A crude ginseng extract (GS) and the purified ginsenoside R(b1) (R(b1)) were
      evaluated for their adjuvant effects in dairy cattle at immunisation with
      ovalbumin (OVA) and/or a Staphylococcus aureus bacterin used for prevention of
      bovine mastitis. To evaluate a suitable dose of GS as an adjuvant, 36 lactating
      cows were randomly divided into six groups. The cows were inoculated twice
      intramuscularly with a 2-week interval, with saline solution, OVA in saline, or
      OVA in combination with 4, 16 or 64 mg GS, or Al(OH)(3). The level of specific
      antibodies to OVA in serum and milk whey was measured before immunisations and 1
      5 weeks after the second immunisation. The antibody response in serum was
      significantly higher in animals immunised with OVA and GS than in animals
      immunised with OVA alone. A significant increase in milk antibody titres compared
      with OVA only was only found 2 weeks after the second immunisation in the group
      immunised with OVA and 4 mg GS. In the second part of the study, 18 heifers were
      randomly divided into three groups and were immunised twice intramuscularly with
      a two week interval, with the S. aureus bacterin (control), or with the bacterin
      in combination with 4 mg GS or 1mg R(b1). The specific antibody response to S.
      aureus and the lymphocyte proliferation after stimulation with PWM, concanavalin
      A (Con A) or a specific S. aureus antigen was evaluated in blood samples taken
      before and after immunisations as specified above. Addition of R(b1) resulted
      both in significantly higher antibody production and lymphocyte proliferation in
      response to PWM, Con A and S. aureus antigens than in the control group. Addition
      of GS induced a significantly higher lymphocyte proliferation in response to PWM
      and Con A than the control, but had no additional effect on the antibody
      production. In conclusion, both GS and R(b1) were safe adjuvants, and R(b1) had
      the strongest adjuvant effects, when used for immunisation against S. aureus in
      dairy cattle. Field trials are warranted to test the ability of GS and R(b1) to
      enhance the efficacy of mastitis vaccines in protection against intramammary
      infections.

PMID- 12507848
TI  - Effects of live attenuated and killed Salmonella vaccine on T-lymphocyte mediated
      immunity in laying hens.
AB  - The impact of live and killed Salmonella vaccines on cell-mediated immunity (CMI)
      was investigated in 18- and 32-week-old White Leghorn chickens, by assessing
      splenic lymphocyte proliferation, expression of IL-2 mRNA in concanavalin A (Con
      A) stimulated cells and flow cytometric analysis of cell subpopulations. Con A
      and Salmonella enteritidis (SE) flagella induced proliferation of splenocytes
      were enhanced in the 18- and 32-week-old chickens treated with live vaccine,
      compared to the corresponding control chickens. Among the killed vaccine treated
      birds, Con A-mediated response was higher in the 18-week-old chickens compared to
      the corresponding control birds. Increased proliferation was accompanied by
      increased CD4 and reduced CD8 and gammadelta T-lymphocytes in the 18-week-old
      live vaccine treated chickens. Relative expression of IL-2 mRNA in Con A
      stimulated splenocytes from 18-week-old birds was not affected by vaccine
      treatment. Overall, live vaccine was more effective in increasing the lymphocyte
      proliferation to Con A as well as SE antigen. This enhanced CMI may prove
      beneficial in protecting chickens against SE infection.

PMID- 12507849
TI  - Simultaneous quantitation of equine cytokine mRNAs using a multi-probe
      ribonuclease protection assay.
AB  - A rapid multi-probe ribonuclease protection assay (RPA) was developed to
      quantitate equine-specific cytokine mRNA levels in activated equine monocyte
      derived macrophages (EMDM) and equine peripheral blood mononuclear cells (EPBMC).
      Eleven template plasmids specific to 10 equine cytokine genes and the beta-actin
      gene were generated from which radiolabeled anti-sense RNA probes were produced.
      The multi-probe RPA simultaneously quantitated mRNA levels of equine IL-1alpha,
      IL-1beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, IFN-gamma, TGF-1beta and TNF
      alpha in EPBMC and EMDM with coefficients of variation as low as 0.03-0.08 (3-8%)
      when normalized to beta-actin expression. This sensitive and rapid assay provides
      a valuable tool for studies of equine immune responses.

PMID- 12507850
TI  - Anti-insulin antibodies in dogs with naturally occurring diabetes mellitus.
AB  - The presence of anti-insulin antibodies was determined by ELISA in serum samples
      from 30 diabetic dogs receiving bovine insulin therapy and 30 normoglycaemic
      dogs. Twenty of the diabetic dogs had significant reactivity to both bovine
      (heterologous) and porcine (homologous) insulin compared to control dogs. In
      contrast there was no significant difference between the two populations in
      reactivity to canine distemper virus (CDV) or canine thyroglobulin. The high
      degree of correlation between anti-bovine insulin and anti-porcine insulin
      antibodies suggested cross-reactivity which was confirmed by performing a
      competition ELISA, with antibody binding to bovine insulin inhibited by pre
      incubating serum with porcine insulin. The insulin B-chain, rather than the A
      chain was the most reactive component of the insulin molecule although in some
      cases, diabetics with antibody reactivity to whole insulin protein showed minimal
      reactivity to the individual subunits. The data suggest that treatment of
      diabetic dogs with bovine insulin can lead to anti-insulin antibody production.
      These antibodies cross-react with homologous insulin and recognise conformational
      as well as linear epitopes.

PMID- 12507851
TI  - The effect of strenuous exercise on mRNA concentrations of interleukin-12,
      interferon-gamma and interleukin-4 in equine pulmonary and peripheral blood
      mononuclear cells.
AB  - The effect of strenuous exercise on the mRNA concentrations of interleukin-12p35
      subunit (IL-12p35), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in
      equine pulmonary and peripheral blood mononuclear cells (PBMCs) was investigated.
      We hypothesized that strenuous exercise would suppress the expression of IL
      12p35, IFN-gamma and augment the expression of IL-4. Eleven horses were randomly
      divided into two groups, a stall-confined control group (n=5) and an exercise
      conditioned treatment group (n=6). Bronchoalveolar and PBMCs were obtained from
      horses in the treatment group prior to the commencement of a 9-week conditioning
      program and 24h after the completion of a maximum exercise test conducted in week
      12. Samples were obtained simultaneously from control horses. Differential counts
      were performed on the bronchoalveolar lavage cells. Real-time PCR was performed
      on the pulmonary and PBMCs to quantitate cytokine expression using equine
      specific primers and Taqman probes. Target gene expression was normalized to 18s
      rRNA expression. With the exception of IL-4 in the BALF cells, mRNA for the three
      cytokines was detected in the mononuclear cells from all horses at both sampling
      times. There were no significant differences in the cytokine mRNA concentrations
      between the two groups of horses at either of the sampling times. These findings
      demonstrate that strenuous treadmill exercise does not exert a deleterious effect
      on gene expression for IL-12p35, IFN-gamma or IL-4 when assessed in horses 24h
      following the intense physical activity.

PMID- 12507852
TI  - Immunohistochemical staining of IFN-gamma positive cells in porcine reproductive
      and respiratory syndrome virus-infected lungs.
AB  - Paraffin-embedded lungs were obtained from a previous porcine reproductive and
      respiratory syndrome virus (PRRSV)-challenged experiment involving three groups:
      an uninfected control group, a low virulence (LV, Resp PRRSV/Repro)-infected
      group, and a high virulence (HV, VR-2385)-infected group. Tissues were collected
      at 3, 7, 10, 14 or 28 days post-inoculation (DPI) (n=5). Lungs were examined to
      detect IFN-gamma positive cells by immunohistochemical staining using polyclonal
      antibodies to IFN-gamma. The microscopic lung lesions induced by the HV group
      were more severe than those in the LV group. A significant increase in number of
      lymphocytes in the HV group was observed at 10 DPI (24.90+/-9.79%), 14 DPI
      (22.00+/-11.47%) and 28 DPI (28.95+/-15.11%) (P<0.05). A relative decrease in
      macrophage numbers was observed and correlated well with the increase in
      lymphocyte numbers when the disease progressed. IFN-gamma positive cells were
      demonstrated in both lymphocytes and macrophages, particularly pulmonary alveolar
      macrophages. A significant increase in IFN-gamma positive cells was found at 7
      DPI (15.90+/-13.65%), 10 DPI (46.95+/-13.79%), 14 DPI (10.90+/-5.13%) and 28 DPI
      (13.40+/-4.89%) in the HV group (P<0.05). The results suggested that the increase
      in IFN-gamma positive cells in the HV group correlated well with the severity of
      the lung lesions, which may be because of the presence of PRRSV in the lung.

PMID- 12507853
TI  - Epidemiological assessment of rinderpest surveillance and control in Uganda
      between 1990 and 1998.
AB  - Based on passive and active data, we report on an epidemiological assessment of
      surveillance and control of rinderpest (RP) in Uganda between 1990 and 1998.
      Active data were collected by administration of questionnaires to animal health
      personnel and their auxiliaries and to stockowners in six selected districts of
      eastern and northeastern Uganda. Passive data were extracted from vaccination and
      seromonitoring reports, and from field and laboratory reports. RP events were
      classified as "confirmed outbreaks", "suspected outbreaks" and "rumours". The
      classification of 56% of the RP events as "suspected outbreaks" indicates the
      difficulty in investigating disease outbreaks in Uganda. Although vaccination
      coverage and seroprevalence were <85% (the recommended target), they nevertheless
      corresponded well-reflecting effective vaccination. However, because of the low
      seroprevalence, a sizable population of cattle in Uganda remained at risk of RP.
      The agreement between the local and national disease reporting systems was low-to
      moderate (kappa=0.39); this indicates inefficiency in disease reporting. Risk
      factors for RP outbreaks were cattle raids and communal grazing. Based on
      overlaid thematic maps of seroprevalence, vaccination coverage and RP events,
      close spatial and temporal associations were observed between cattle raids,
      transhumance and outbreaks and rumours. The high-risk areas were in the eastern
      and northeastern parts of the country. The results of this study support a phase
      approach of following the OIE pathway.

PMID- 12507854
TI  - A questionnaire-based, retrospective field study of persistence of Salmonella
      Enteritidis and Salmonella Typhimurium in Danish broiler houses.
AB  - A questionnaire-based, retrospective field study was conducted in 78 Danish
      broiler houses (analytical units) on 42 farms. In spring 1997, all these broiler
      houses had been infected with Salmonella Enteritidis, phage type 8, and/or
      Salmonella Typhimurium, definitive-type 66, by day-old chicks delivered from the
      same hatchery. Because these two salmonella types had not been detected in the
      Danish broiler sector before and the broiler houses were infected in a period of
      low salmonella prevalence, the study could focus on farm-related factors, without
      being distorted by other salmonella infections. The same person visited all 78
      broiler houses, and farm-related factors were listed both from personal
      observations and by interrogating the person in charge of attending to the
      broilers. Additional factors (noted at the visits) were recorded in a later
      telephone interview. Altogether, 187 variables were analyzed.Broiler houses were
      divided into single-infection houses (which had one or both of the salmonella
      types in only one crop), and multiple-infection houses (where infection occurred
      in multiple crops). This was done both generally and separately for each of the
      salmonella types. Factors associated with house status-but that were beyond the
      control of the farmer-were the salmonella type and the percentage of salmonella
      positive samples in the first crop. Factors which could be controlled by the
      farmer and which were associated with reduced prevalence of multiple-infection
      houses included antiseptic soap and water for washing hands in the anteroom,
      hygiene barriers when removing dead broilers, gravel alongside the broiler house,
      systematic checks of indoor rodent-bait depots, and combined surface and pulse
      fogging disinfection.

PMID- 12507855
TI  - Effect of previous antimicrobial treatment on fecal shedding of Salmonella
      enterica subsp. enterica serogroup B in New York dairy herds with recent clinical
      salmonellosis.
AB  - The association of herd- and sample-level factors with the isolation of
      Salmonella group B from cattle fecal samples was analyzed. Study farms were 65
      dairy herds with a recent history of laboratory-confirmed clinical salmonella
      infections. Herds were visited once per month for three months to collect data
      and samples for bacteriological culture. Herd size varied widely from 34 to 3700
      total cattle on the farm (median=370). Salmonella serogroup B was isolated from
      270 of 2726 samples tested. The predominant serotypes identified were S.
      Typhimurium and S. Typhimurium var. Copenhagen. Logistic regression was used to
      analyze the relationship between potential risk factors and isolating Salmonella
      serogroup B. The only herd-level factor which was significantly associated with
      fecal shedding was total herd size (hundreds of cattle OR=1.09; 95% confidence
      interval (CI): 1.05, 1.14). The probability of a positive sample decreased
      substantially for longer intervals between the initial clinical case and sampling
      (interval in months OR=0.5; 95% CI: 0.3, 0.6). The presence of diarrhea increased
      the risk of shedding (OR=2.1; 95% CI: 1.4, 3.0). The effect of recent treatment
      with antimicrobial agents depended on age group. For heifers and cows, recent
      antimicrobial treatment increased the probability of isolating Salmonella
      (heifers OR=11.8; 95% CI: 2.9, 48.8; cows OR=4.1; 95% CI: 2.0, 8.4), but this
      effect was not statistically significant for calves before weaning. Among animals
      without recent antimicrobial treatment, preweaned calves were more likely to have
      positive samples than cows (OR=3.5; 95% CI: 1.8, 6.9; heifers OR=4.7; 95% CI:
      2.3, 9.6).

PMID- 12507856
TI  - Spatial analysis of Yersinia pestis and Bartonella vinsonii subsp. berkhoffii
      seroprevalence in California coyotes (Canis latrans).
AB  - Zoonotic transmission of sylvatic plague caused by Yersinia pestis occurs in
      California, USA. Human infections with various Bartonella species have been
      reported recently. Coyotes (Canis latrans) are ubiquitous throughout California
      and can become infected with both bacterial agents, making the species useful for
      surveillance purposes. This study examined the geographic distribution of 863
      coyotes tested for Y. pestis and Bartonella vinsonii subsp. berkhoffii serologic
      status to gain insight into the natural history of B. vinsonii subsp. berkhoffii
      and to characterize the spatial distribution of the two agents. We found 11.7% of
      specimens positive to Y. pestis and 35.5% positive to B. vinsonii subsp.
      berkhoffii. The two pathogens had distinct spatial clusters: Y. pestis was more
      prevalent in eastern portions of the state and B. vinsonii subsp. berkhoffii in
      coastal regions. Prevalence of Y. pestis increased with increasing elevation,
      whereas prevalence of B. vinsonii subsp. berkhoffii decreased with increasing
      elevation. There were differences in the proportions of positive animals on a
      yearly basis to both pathogens.

PMID- 12507857
TI  - Effect of covering pig slurry stores on the ammonia emission processes.
AB  - The aim of this study was to evaluate the effects of different covers (oil,
      plastic film, perforated polystyrene float, peat and zeolites) on slurry settling
      characteristics and ammonia emission during storage and following surface
      application in the field. Laboratory trials were carried out for 15 days using a
      pilot scale device. Samples of 5 kg slurry were used. At the end of the storage
      period, distributions of dry matter, pH, total ammoniacal nitrogen and total
      Kjeldahl nitrogen in slurry were characterized. In the field, ammonia
      volatilisation was measured for three days using a wind tunnel system. Oil and
      plastic film retained all ammoniacal nitrogen forms in the slurry, whereas the
      others reduced ammonia volatilisation by reducing the emitting surface or by
      adsorbing/absorbing ammonia. Over the whole process studied (storage plus
      application) ammonia emissions were reduced by 40% by oil up to 65-71% by
      zeolites with different particle sizes.

PMID- 12507858
TI  - Reaction conditions for laccase catalyzed polymerization of catechol.
AB  - Poly(catechol) was synthesized in batch runs with laccase from Trametes
      versicolor (ATCC 200801). The polymerization reaction was conducted in a closed,
      temperature controlled system containing acetone and sodium acetate buffer for pH
      control. The effects of the solvent mixture, monomer (catechol), enzyme, medium
      pH and temperature on the polymerization rate were investigated with respect to
      initial reaction conditions and depletion rate of dissolved oxygen in the medium.
      Maximum initial reaction rate was attained with 10% (v/v) acetone-sodium acetate
      buffer at pH 5.0, 25 degrees C, 0.02 U/ml enzyme and 250 mg/l initial catechol
      and 10 mg/l dissolved oxygen. A general saturation enzyme kinetics response was
      observed for catechol substrate. Temperature rise supported the rate increase up
      to 45 degrees C, after which the rate tended to be stable due to a drop in
      dissolved oxygen concentration as well as enzyme instability.

PMID- 12507859
TI  - The effect of ohmic heating on vacuum drying rate of sweet potato tissue.
AB  - Ohmically heating fruit and vegetable tissue has been shown to increase hot-air
      drying rate, shift desorption isotherms, and increase juice extraction yields
      with respect to untreated, conventionally heated, and microwaved samples. The
      objective of this study was to determine if ohmically heating sweet potato tissue
      would enhance the vacuum drying rate of these samples with respect to untreated
      samples. Sweet potato cubes were ohmically heated to three endpoint temperatures
      using three electrical field strengths and were then placed in a freeze dryer.
      Moisture content vs. time data were collected and modeled. Results showed that
      the vacuum drying rates of ohmically heated samples were faster than raw samples
      for most treatment combinations, and that the maximum reduction of drying time
      was 24%. Minimal ohmic treatment can result in a significant decrease in vacuum
      drying time, which could have important economic and product quality
      implications.

PMID- 12507860
TI  - Dye adsorption by sewage sludge-based activated carbons in batch and fixed-bed
      systems.
AB  - The present research work deals with the production of activated carbons by
      chemical activation and pyrolysis of sewage sludges. The adsorbent properties of
      these sewage sludges based activated carbons were studied by liquid-phase
      adsorption tests. Dyes removal from colored wastewater being a possible
      application for sludge based adsorbents, methylene blue and saphranine removing
      from solution was studied. Pure and binary adsorption assays were performed in
      batch and fixed bed systems. In all cases studied, the adsorbents produced from
      sewage sludges were able to adsorb both the compounds considered here.
      Nevertheless, time required for reaching equilibrium, adsorptive capacity and
      fixed bed characteristic parameters were different for these two compounds.
      Methylene blue adsorption occurred faster than that of saphranine, and it was
      preferably adsorbed when treating binary solutions. It could be concluded that
      the sewage sludge-based activated carbons may be promising for dyes removal from
      aqueous streams.

PMID- 12507861
TI  - Physical-mechanical properties and chemical composition of Pinus taeda mature
      wood following a forest fire.
AB  - The objective of this study was to assess the effects of heat released during
      forest fires on wood properties of Pinus taeda L. trees submitted to different
      burning levels (increasing fire intensity, I-IV). Wood samples were collected
      from trees in each of the burning levels and also from trees not affected by fire
      (control). Specimens were then extracted to evaluate the physical and mechanical
      wood properties; chemical composition was evaluated only for burning level IV and
      control. The analysis of the results showed that fire effects over the physical
      mechanical properties and chemical composition in all burning levels did not
      cause sufficient chemical degradation and strength reduction, which could be
      cause for rejection of those woods for normal use. In the case of structural use
      caution should be adopted for the wood from burning levels III and IV, which had
      their mechanical property values reduced.

PMID- 12507862
TI  - Use of xylan, an agricultural by-product, in wheat gluten based biodegradable
      films: mechanical, solubility and water vapor transfer rate properties.
AB  - The possibility of using xylan, as an agricultural by-product, for production of
      composite films in combinations with wheat gluten was investigated. Different
      levels of xylan (0-40% w/w) were incorporated into wheat gluten to form
      biodegradable composite films. Films were prepared at pH 4 and 11, and dried at
      either uncontrolled or controlled conditions. The mechanical properties,
      solubilities and water vapour transfer rate (WVTR) of the composite films were
      studied. Films were obtained with added xylan without decreasing film-forming
      quality. Xylan can be used as an additive, as much as 40% (w/w), in wheat gluten
      films. Changing pH, wheat gluten/xylan ratio, xylan type and drying conditions
      affected mechanical and solubility properties, however, WVTR was not affected by
      xylan additions. Wheat gluten/xylan composite films having different
      characteristics can be produced depending on xylan type, composition and process
      conditions.

PMID- 12507863
TI  - The effect of pH on the foam fractionation of beta-glucosidase and cellulase.
AB  - The surface tension-pH profile of beta-glucosidase was established to determine
      its relationship to the corresponding profile of cellulase and to the foam
      fractionation of that cellulase. The goal of this work was to determine the
      optimal foaming points for both cellulase and cellobiase. This data may prove
      useful in the separation of certain components of cellulase, since the non
      foaming hydrophilic beta-glucosidase does not foam as well as the hydrophobic
      components of cellulase at low concentrations. A key finding from these
      experiments was that there are two local minima in the surface tension-pH
      trajectory for Trichoderma reesei cellulase, as contrasted to the usual single
      minimum. The lower of these minimum points corresponds to the cellulase
      isoelectric point. The double minimum surface tension-pH profile was also
      observed for cellobiase alone. The optimal foaming pH for cellobiase alone was
      determined to be around 10.5, while for cellulase it was between 6 and 9.

PMID- 12507864
TI  - Optimization of hydrogen peroxide in totally chlorine free bleaching of cellulose
      pulp from olive tree residues.
AB  - The influence of the operating conditions used in the bleaching of olive wood
      trimmings pulp (viz. hydrogen peroxide concentration and time) on the yield,
      kappa index and viscosity of the resulting pulp and on strength-related
      properties of paper sheets was studied to determine the optimal bleaching
      conditions of this pulp. Hydrogen peroxide bleached pulps at different sequences
      (oxygen, ozone, chlorine dioxide and alkaline extractions) were compared.
      Hydrogen peroxide bleaching proved to be suitable for this pulp. Considerable
      improvements in viscosity were obtained with respect to other bleaching sequences
      such as oxygen, ozone and chlorine dioxide. Hydrogen peroxide bleaching decreased
      the kappa index 51.3% less than ozone bleaching, 25.0% less than chlorine dioxide
      (D) and 6.3% less combined chlorine dioxide-alkaline extraction (DE). To obtain
      kappa indices 50.9% and 37.9% lower than the index achieved by hydrogen peroxide,
      oxygen (LaO(p)) and ozone (LaO(LaZ)R) sequences respectively were needed. Lower
      medium levels of hydrogen peroxide concentrations (1-3%) and high reaction times
      (210 min) proved to be suitable for bleaching of pulp olive trimming residues.
      This approach could be used on this residue to produce adequately bleached pulp.

PMID- 12507865
TI  - Water quality, biofilm production and growth of fringe-lipped carp (Labeo
      fimbriatus) in tanks provided with two solid substrates.
AB  - The effects of two substrates, sugarcane bagasse (T(1)) and paddy straw (T(2)) on
      water quality and growth of Labeo fimbriatus were studied in mud-bottomed,
      manured cement tanks, in triplicate; a set of three tanks without substrate
      served as control (T(3)). Addition of manure and substrate brought about a
      decrease in dissolved oxygen level, but it stabilized after 15 days, when the
      tanks were stocked with 30 fish each, fed at 3% body weight daily and reared for
      90 days. Total ammonia content in substrate based treatments was relatively lower
      than in the control. Significantly higher nitrite-nitrogen was recorded in the
      control tanks. The total plate counts (TPC) of bacteria in water did not differ
      significantly between treatments and control. The overall mean value of TPC with
      substrate was higher in T(2) than in T(1). The mean phytoplankton density in
      water was the highest in T(1), followed by T(3) and T(2), whereas zooplankton
      density was the highest in T(1) followed by T(2) and T(3). The growth of fish was
      significantly (P<0.05) higher in substrate-based tanks, the percentage increases
      over control being 30.44 (T(1)) and 28.71 (T(2)) respectively. Higher RNA, DNA
      and RNA:DNA ratios were recorded under T(1), followed by T(2) and T(3). Higher
      enzyme activity was observed in fish from substrate treatments, which was
      attributable to the additional nutrients derived through the biofilm. The results
      demonstrated that production of L. fimbriatus can be significantly increased by
      the introduction of biodegradable substrates into culture systems where
      fertilization and feeding are employed.

PMID- 12507866
TI  - Removal of total lipids and fatty acids from sunflower oil factory effluent by
      UASB reactor.
AB  - In this study wastewaters of a sunflower oil factory in Elazig (Turkey) were
      investigated in a pilot-scale mesophilic upflow anaerobic sludge blanket (UASB)
      reactor by determination of removal of total lipids (TL) and fatty acids (FA).
      The removal efficiencies of TL and FA (linoleic, oleic, myristic, palmitic,
      stearic, arashidic, behenic and other FA) were above 70% at organic loading rates
      (OLR) between 1.6 and 7.8 kg COD/m(3)d and at optimum hydraulic retention times
      of 2.0 and 2.8 day. The conversion rate of removed COD to methane was between
      0.16 and 0.354 m(3) CH(4)/kg COD.

PMID- 12507867
TI  - Influence of an organic mulching on fertilizer nitrogen use efficiency and herb
      and essential oil yields in geranium (Pelargonium graveolens).
AB  - In a field study, conducted at Lucknow ( 26.5 degrees N, 80.5 degrees E and 120 m
      altitude), India for two years (1996-1997 and 1997-1998), eight treatment
      combinations of two variables of organic mulch (paddy straw at 7 t/ha and no
      mulch) and four levels of fertilizer nitrogen (0, 80, 160 and 240 kg/ha) were
      examined to observe the effect of organic mulching on N-use efficiency and
      essential oil yield in a multi-harvested geranium crop. Results revealed that
      application of paddy straw mulch increased the herb and essential oil yields in
      geranium by 23% and 27%, respectively, over the unmulched control at planted crop
      harvest. Corresponding values at regenerated crop harvest were 18.7% and 19.2%. A
      significant response to N was observed with 160 kgN/ha in mulched plot over the
      same level of N in the unmulched plot. Using paddy straw mulch, nitrogen uptake
      by plants of planted and regenerated crops was increased by 33% and 28.4%,
      respectively, over the unmulched control. Apparent N recoveries by planted and
      regenerated crops were estimated to be 33.7% and 22.7% for the unmulched control,
      as against 40% and 29.2% with paddy straw mulch at 160 kgN/ha. The quality of
      essential oil of geranium in terms of its major constituents, citronellol and
      geraniol, was not affected by the use of organic mulching and nitrogen
      fertilization and these constituents were found to be of a standard acceptable in
      international trade. It was concluded from this study that use of an organic
      mulch with 160 kgN/ha proved better in terms of economising 80 kgN/ha to produce
      an economic yield of 96.1 kg geranium oil from two harvests under subtropical
      conditions of the north Indian plains. At 160 kgN/ha, paddy straw mulch
      application permitted the geranium crop to produce 18.4 kg/ha more oil which gave
      an additional return of Rs. 53,600/ha than that of unmulched control. Paddy straw
      mulch and nitrogen fertilization had no adverse effect on the quality of
      essential oil of geranium.

PMID- 12507868
TI  - Effects of farmyard manure and phosphorus on zinc transformations and phyto
      availability in two alfisols of India.
AB  - Laboratory pot experiments were run to study the effects of added zinc (Zn) with
      and without farmyard manure (FYM) and phosphorus (P) on Zn transformations in two
      Alfisols, together with Zn uptake by wheat plants grown up to 60 days. In the
      first experiment the treatments included four levels of Zn (0, 3.75, 7.5 and 15
      mgkg(-1) soil) and two levels of FYM (0 and 10 tha(-1)), and in the second
      experiment five levels of P (0, 20, 40, 80 and 160 mgkg(-1) soil) and one level
      of Zn (7.5 mgkg(-1) soil). The soils were sequentially fractionated into water
      soluble plus exchangeable (CA-Zn), inorganically bound (AAC-Zn), organically
      bound (PYR-Zn), oxide bound (OX-Zn) and residual (RES-Zn) forms. The effect of
      added FYM was more evident on the OX-Zn fraction and the percentage utilization
      of Zn by wheat was the greatest with the addition of FYM alone at the rate of 10
      tha(-1) (1.95-2.38%) in comparison to other treatment combinations. Among the
      levels, application of 7.5 mg Zn kg(-1) soil showed the maximum increase in
      different fractions of soil Zn and significantly increased the Zn utilization by
      wheat (0.87-1.17%) as compared to other Zn levels (0.58-0.88%). On an average,
      about 85% of the added Zn was recovered in different fractions in Zn treated
      pots. However, the recovery per cent of the added Zn was significantly higher at
      Zn level 7.5 (95%) mgkg(-1) soil than at 3.75 (87%) and 15 (73%) mg Zn kg(-1)
      soil levels. Phosphorus additions up to 40 mgkg(-1) soil increased the plant
      available Zn in soils whereas at higher P levels plant-available forms decreased
      with a concominant increase in the inert forms. At 160 mg P kg(-1) soil, the P
      effect was more pronounced in the shoot than in the root, suggesting that a
      higher P level inhibits Zn translocation from root to upper plant parts. Path
      analysis showed that the organically (PYR-Zn) and inorganically bound (AAC-Zn) Zn
      fractions were the predominant fractions that influenced the Zn availability to
      plants.

PMID- 12507869
TI  - Emissions modeling of fluidised bed co-combustion of poultry litter and peat.
AB  - Gaseous emissions from the fluidised bed co-combustion of 50% w/w chicken litter
      and peat were monitored and recorded. Emission data were used to create a
      dispersion model for a proposed site on a poultry farm in Ireland. Variables
      within the combustion unit influenced both combustion and emission levels of
      pollutants such as SO(2) and NO(x), CO. Concentrations of atmospheric pollutants
      decreased with use of the correct ratio between fluidising and secondary air.
      Dispersion modelling of combustion at a proposed poultry unit predicted that
      ground level concentrations for the set of emissions data would be below the
      limits and guidelines set by air quality standards.

PMID- 12507870
TI  - Thermo-acido-tolerant phytase production from a soil bacterium in a medium
      containing rice bran and soybean meal extract.
AB  - A bacterial strain capable of producing a thermo-acido-tolerant phytase was
      isolated from soil around haystacks and designated as strain PH01. The phytase
      produced was purified to homogeneity as determined by native PAGE. From SDS-PAGE,
      it was 30 kDa in size. The purified phytase was a thermo-acido-tolerant enzyme. A
      complex medium for the PH01 phytase production was developed. The medium, "PheB",
      was composed of 2% glucose, 0.2% CaCl(2), 0.5% NH(4)NO(3), 0.05% KCl, 0.05%
      MgSO(4).7H(2)O, 0.001% FeSO(4).7H(2)O, 0.001% MnSO(4).H(2)O in rice bran plus
      soybean meal extract containing 3% (v/v) phosphate solution (7.3%
      NaHPO(4)+3.2%KH(2)PO(4), pH 7.2). Cultivation was done at 37 degrees C with
      aeration for 48 h which produced phytase at 10 U/ml. Exposure of the phytase to
      1% bile salt; i.e., taurocholate or deoxycholate, caused less than 15% reduction
      of activity. Potential application of PH01 phytase as a feed supplement was
      suggested.

PMID- 12507871
TI  - Effect of propionate toxicity on methanogenesis of night soil at phychrophilic
      temperature.
AB  - The effect of propionate concentrations on biodegradation of human waste (night
      soil) was studied at 10 degrees C. Propionate was toxic for the biomethanation at
      all the pH tested (6.0, 7.0 and 8.0). The maximum reduction in biogas production
      in presence of 200 mM propionate was observed at pH 7.0 followed by 8.0. The
      methane content in biogas also followed a similar trend and at pH 7.0 an 11.5%
      decrease was observed. Propionate caused the reduction of methanogenic count by
      an approximately 2log value. Total volatile fatty acids increased with the
      increase in propionate concentration and particularly accumulation of propionate
      was observed. The results were also compared with the 30 degrees C fermentation.

PMID- 12507872
TI  - TCF bleaching of wheat straw pulp using ozone and xylanase. Part A: paper quality
      assessment.
AB  - The XOAZRP TCF sequence was applied to bleach wheat straw pulp. Following each
      bleaching stage, the properties of the pulp (viz. kappa number, standard
      viscosity, borohydride viscosity and brightness) and of the resulting effluents
      were determined. The performance of the reagents was analyzed through the studies
      of xylanase treatment and crystallinity and scanning electron microscopy of the
      pulps. Finally, the pulp was refined at 1000 revolutions in a PFI mill and the
      mechanical properties of the resulting paper were determined and compared with
      those of paper from a eucalyptus pulp. Despite its shortcomings, wheat straw pulp
      can be effectively bleached with the proposed TCF sequence.

PMID- 12507873
TI  - TCF bleaching of wheat straw pulp using ozone and xylanase. Part B: kinetic
      studies.
AB  - The reaction kinetics of ozone bleaching of wheat straw pulp has been studied for
      the first time. The results were compared with eucalyptus pulp in order to know
      that both raw materials have a similar behaviour. Ozone treatments were carried
      out in a special reactor at low consistency (0.5% o.d.p.). The main variables
      were consumption of ozone by the pulp and application of a xylanase treatment (X)
      prior to the oxygen stage (O). The responses measured were kappa number,
      viscosity and brightness, to give the kinetic expressions for delignification,
      cellulose degradation and elimination of chromophore groups, along with
      calculation of selectivity. Cellulose degradation and elimination of lignin and
      chromophore groups show first-order kinetics in all cases. The kinetics of the
      enzyme pre-treatment effect shows similar behaviour in both raw materials,
      although the constants of delignification and elimination of chromophore are
      higher in straw pulp.

PMID- 12507874
TI  - Impregnation of softwood cell walls with melamine-formaldehyde resin.
AB  - Melamine-formaldehyde (MF) resin impregnation has shown considerable potential to
      improve a number of wood properties, such as surface hardness and weathering
      resistance. In this study, selected factors influencing the uptake of MF resin
      into the cell wall of softwood were studied. Using UV-microspectroscopy, it could
      be shown that water soluble MF diffused well into the secondary cell wall and the
      middle lamella. Concentrations as high as 24% (v/v) were achieved after an
      impregnation of 20 h. High cell wall moisture content, high water content of the
      resin used for impregnation, and low extractive content are factors which are
      favourable for MF resin uptake into the cell wall. For dry cell walls, solvent
      exchange drying improved resin uptake to a similar extent, as was the case when
      cell walls were soaked in water.

PMID- 12507875
TI  - Respiration profiles in monitoring the composting of by-products from the olive
      oil agro-industry.
AB  - The composting of olive press cake (OPC) repeatedly mixed either with olive mill
      wastewater (OPC+OMW) or with tap water (OPC+W) was studied using the
      thermogradient respirometer, an apparatus that determines the respiration rates
      from a substrate over a wide range of different temperatures (respiratory
      profile). The composting processes took place over a period of five months during
      which nine moistenings of the OPC were performed with the respective liquids. The
      composting resulted in detoxification of the materials used in both treatments,
      as indicated by seed germination tests. However, the repeated applications of OMW
      resulted in recurring thermophilic phases (following each application) and in
      greater pH and conductivity increases in the final product, as compared to water
      applications. Respiration measurements performed at 35 degrees C were good
      indicators of the mean metabolic potential in the compost piles (the mean
      respiration derived from the whole respiration profile over a wide range of
      environmental temperatures). However, respiration measurements at higher
      temperatures (48.5 degrees C) were better indicators of the respiration activity
      occurring in situ. Following the initial thermophilic phase, the respiration
      potential of the composts at high temperatures (42-63 degrees C) increased
      drastically compared to their respiration potential at lower temperatures (17-42
      degrees C) indicating the establishment of a thermophilic microflora.
      Subsequently, only the periodic new substrate-C applications in the form of OMW
      resulted in increased ratios of low temperature-to-high temperature respiration
      potential. These ratios decreased again following the respective thermophilic
      phase that each new OMW application had induced.

PMID- 12507876
TI  - Grape and apple wines volatile fermentation products and possible relation to
      spoilage.
AB  - The main volatile by-products of the alcoholic fermentation of grape wine, cider
      and apple pulp wine were investigated to determine if any correlated with
      spoilage resistance in the latter two. Spoilage was visually detected after seven
      days in low-alcohol grape wine in comparison to 11 and 16 days in cider and apple
      pulp wine, respectively. Acetaldehyde, ethyl acetate, methanol, propanol,
      isobutanol and amyl alcohols were the main fermentation by-products detected in
      all three wines. There were highest concentrations of acetaldehyde, ethyl
      acetate, methanol and propanol in grape wine and, therefore, these by-products
      could not be implicated in spoilage resistance in apple wines. Increased
      concentrations of isobutanol and amyl alcohols, however, in cider and apple pulp
      wine in comparison to grape wine might have been the reason for spoilage
      resistance in the apple wines.

PMID- 12507877
TI  - Soil response to eucalypt tree planting and meatworks effluent irrigation in a
      short rotation forest regime in New Zealand.
AB  - The effects of planting three eucalypt species and irrigating with meatworks
      effluent on soil were assessed during the first 3-year rotation of a short
      rotation forest regime at Oringi, Dannevirke, New Zealand. The results showed
      tree planting alone reduced the soil infiltration rates, but had little influence
      on soil nutrient concentration other than reduction of nitrate levels. Species
      variation had limited influence on soil change. Effluent irrigation relieved the
      reduction of infiltration rates by tree planting, and increased nutrient
      concentrations, but reduced the soil pH. These changes should be considered when
      managing eucalypt short rotation forests sustainably in the longer term, either
      linked with effluent irrigation or not.

PMID- 12507878
TI  - Effect of veneer side wettability on bonding quality of Eucalyptus globulus
      plywoods prepared using a tannin-phenol-formaldehyde adhesive.
AB  - The influence of rotary peeling on the different behaviour of tight and loose
      sides of Eucalyptus globulus veneers has been studied. The presence of lathe
      checks on the loose sides favours wettability, the contact angle decreasing more
      rapidly on these sides than on tight sides. Additionally, pine bark tannins
      improved wettability due to their surfactant character. Bonding quality tests
      carried out on plywoods prepared using a tannin-phenol-formaldehyde adhesive
      showed that fracture almost invariably occurred in a glue line with at least one
      loose side, where wood failure appeared. This behaviour, confirmed by analysing
      the glue lines by means of fluorescence microscopy, was due to the large surface
      alterations of the loose sides which reduced mechanical strength but allowed
      greater penetration of the adhesive giving rise to high wood failure.

PMID- 12507879
TI  - The removal by crab shell of mixed heavy metal ions in aqueous solution.
AB  - In order to examine the inhibition effect of other heavy metal ions on the
      removal by crab shell of heavy metal ions in aqueous solutions, three ions
      (Pb(2+), Cd(2+), Cr(3+)) were used in single, binary and ternary systems. In
      single heavy metal ion systems, the removals of Cr(3+) and Pb(2+) were much
      higher than that of Cd(2+). In binary heavy metal ions systems, Cd(2+) did not
      affect Pb(2+) removal while Cr(3+) had a severe inhibition effect on the removal
      of Pb(2+). Cd(2+) removal was slightly affected by the presence of Pb(2+);
      however, it was severely affected by the presence of Cr(3+). The inhibitory
      effect of Cd(2+) on Cr(3+) was relatively lower than that of Pb(2+).

PMID- 12507880
TI  - Effect of media supplements and culture conditions on inulinase production by an
      actinomycete strain.
AB  - Streptomyces sp. GNDU 1 produced high levels of extra-cellular inulinase (0.552
      IU/ml) after 24 h at pH 7.5, temperature 46 degrees C in the presence of 1%
      inulin. The optimum temperature and pH for enzyme activity were 60 degrees C and
      5.5 respectively. Yeast extract as a nitrogen source was found to be most
      suitable one for inulinase production whereas ammonium ion was inhibitory to the
      enzymatic production. All these conditions make Streptomyces sp. GNDU 1, a
      potential candidate for industrial enzymatic production of fructose from inulin.

PMID- 12507883
TI  - Keys to the hidden treasures of the mannose 6-phosphate/insulin-like growth
      factor 2 receptor.

PMID- 12507884
TI  - Medulloblastoma in mice lacking p53 and PARP: all roads lead to Gli.

PMID- 12507885
TI  - Up-regulation of macrophage migration inhibitory factor gene and protein
      expression in glial tumor cells during hypoxic and hypoglycemic stress indicates
      a critical role for angiogenesis in glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most malignant variant of human glial
      tumors. A prominent feature of this tumor is the occurrence of necrosis and
      vascular proliferation. The regulation of glial neovascularization is still
      poorly understood and the characterization of factors involved in this process is
      of major clinical interest. Macrophage migration inhibitory factor (MIF) is a
      pleiotropic cytokine released by leukocytes and by a variety of cells outside of
      the immune system. Recent work has shown that MIF may function to regulate
      cellular differentiation and proliferation in normal and tumor-derived cell
      lines, and may also contribute to the neovascularization of tumors. Our
      immunohistological analysis of MIF distribution in GBM tissues revealed the
      strong MIF protein accumulation in close association with necrotic areas and in
      tumor cells surrounding blood vessels. In addition, MIF expression was frequently
      associated with the presence of the tumor-suppressor gene p53. To substantiate
      the concept that MIF might be involved in the regulation of angiogenesis in GBM,
      we analyzed the MIF gene and protein expression under hypoxic and hypoglycemic
      stress conditions in vitro. Northern blot analysis showed a clear increase of MIF
      mRNA after hypoxia and hypoglycemia. We could also demonstrate that the increase
      of MIF transcripts on hypoxic stress can be explained by a profound
      transcriptional activation of the MIF gene. In parallel to the increase of MIF
      transcripts, we observed a significant rise in extracellular MIF protein on
      angiogenic stimulation. The data of our preliminary study suggest that the up
      regulation of MIF expression during hypoxic and hypoglycemic stress might play a
      critical role for the neovascularization of glial tumors.

PMID- 12507886
TI  - Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and
      glioblastoma independently of p53 expression.
AB  - Brain angiogenesis inhibitors (BAI) are putative transmembrane proteins
      containing an extracellular domain with thrombospondin type-1 repeats which can
      exhibit anti-angiogenic activity. BAI1 mRNA is expressed mainly in the brain,
      while BAI2 and BAI3 mRNAs are more widely expressed. We hypothesized that the BAI
      family might have anti-tumoral properties and studied the expression of BAI1
      protein in normal human brain and in glioblastoma multiforme. We generated an
      anti-BAI1 antibody and showed that BAI1 was widely expressed in normal brain but
      was absent in 28 glioma cell lines and in the majority of human glioblastoma
      investigated. BAI1 expression did not correlate with TP53 status and we did not
      confirm previous findings that p53 regulates BAI1 mRNA expression in glioma
      cells. The finding that expression of BAI proteins may be lost during tumor
      formation is of special interest as restoration of their function in tumors may
      be of therapeutic benefit.

PMID- 12507887
TI  - Low frequency of FAS mutations in Reed-Sternberg cells of Hodgkin's lymphoma.
AB  - Reed-Sternberg (RS) cells, the neoplastic elements of Hodgkin's lymphoma (HL),
      usually lack B-cell receptor expression. Normal germinal center B cells, with
      lack of or low-affinity B-cell receptor expression, are eliminated via FAS
      induced apoptosis. RS cells express FAS, but are rescued from apoptosis by a
      transforming event. It is known that HL-derived cell lines are resistant to FAS
      mediated apoptosis. To investigate potential causes for this resistance, FAS
      mutations and c-FLIP expression were studied in four HL-derived cell lines and 20
      cases of HL. L1236 was found to have a splice donor site mutation in intron 7
      that resulted in an aberrantly spliced FAS transcript. Screening of
      microdissected RS cells revealed loss of heterozygosity for a known exon 7
      polymorphism in two of six informative cases indicating loss of one FAS allele.
      In one of the two cases with loss of heterozygosity a hemizygous mutation was
      detected in exon 9. c-FLIP expression was observed in all HL cell lines and in RS
      cells of all HL cases. Our data show that FAS mutations are rare and suggest that
      overexpression of c-FLIP, which was present in all cases, is involved in the
      resistance to FAS-mediated apoptosis.

PMID- 12507888
TI  - Quantitative gene expression analysis reveals transition of fetal liver
      progenitor cells to mature hepatocytes after transplantation in uPA/RAG-2 mice.
AB  - Therapies for liver diseases with stem and progenitor cells will require a
      detailed knowledge of the molecular mechanisms driving the in vivo
      differentiation process toward adult hepatic tissue. We applied quantitative gene
      expression methods to analyze the differentiation process of fetal liver
      progenitor cells after transplantation into an animal model of liver
      regeneration. Enhanced green fluorescent protein (EGFP)-transgenic liver
      progenitor cells were isolated from fetal mouse liver at stage embryonic day 13.5
      and transplanted into uPA/RAG-2 mice. Two, 4, and 6 weeks after cell
      transplantation cryosections of liver tissue were analyzed for EGFP-positive
      regeneration nodules. RNA from laser-microdissected EGFP-positive tissue was
      isolated and used as template for quantitative real-time reverse transcriptase
      polymerase chain reaction. Phenotypic differentiation was analyzed by staining of
      the canalicular marker enzyme dipeptidyl-peptidase IV. Proliferation in
      regenerative nodules and surrounding tissue was monitored with the BrdU
      incorporation assay. Alpha fetoprotein gene expression had already decreased 2
      weeks after transplantation in EGFP-positive regeneration nodules compared to
      pretransplantation values and was not detectable after 4 and 6 weeks, whereas
      albumin slightly increased in transplanted cells indicating differentiation into
      a mature phenotype. The dipeptidyl-peptidase IV antigen was associated with some
      liver progenitor cells 2 weeks after transplantation and in virtually all cells
      after 4 and 6 weeks. Cell proliferation index in transplanted cells was maximally
      increased (4.8% BrdU-positive cells) after 2 weeks and decreased (0.4%) after 6
      weeks to normal levels. Our results demonstrate that gene expression in liver
      progenitor cells changes from fetal to adult phenotype within 4 to 6 weeks after
      transplantation despite ongoing proliferation of the transplanted cells in a
      mouse model of liver regeneration. Quantitative gene expression profiles as shown
      here will have important implications in our understanding of the in vivo
      differentiation process of stem cells.

PMID- 12507889
TI  - Regulation of macrophage migration inhibitory factor expression by
      glucocorticoids in vivo.
AB  - Glucocorticoid hormones are important anti-inflammatory agents because of their
      anti-inflammatory and proapoptotic action within the immune system. Their
      clinical usefulness remains limited however by side effects that result in part
      from their growth inhibitory action on sensitive target tissues. The protein
      mediator, macrophage migration inhibitory factor (MIF), is an important regulator
      of the host immune response and exhibits both glucocorticoid-antagonistic and
      growth-regulatory properties. MIF has been shown to contribute significantly to
      the development of immunopathology in several models of inflammatory disease.
      Although there is emerging evidence for a functional interaction between MIF and
      glucocorticoids in vitro, little is known about their reciprocal influence in
      vivo. We investigated the expression of MIF in rat tissues after ablation of the
      hypothalamic-pituitary-adrenal axis and after high-dose glucocorticoid
      administration. MIF expression is constitutive and independent of the influence
      of adrenal hormones. Hypophysectomy and the attendent loss of pituitary hormones,
      by contrast, decreased MIF protein content in the adrenal gland. Administration
      of dexamethasone was found to increase MIF protein expression in those organs
      that are considered to be sensitive to the growth inhibitory effects of
      glucocorticoids (immune and endocrine tissues, skin, and muscle). This increase
      was most likely because of a posttranscriptional regulatory effect because tissue
      MIF mRNA levels were not influenced by dexamethasone treatment. Finally, MIF
      immunoneutralization enhanced lymphocyte egress from blood during stress-induced
      lymphocyte redistribution, consistent with a functional interaction between MIF
      and glucocorticoids on immune cell trafficking in vivo. These findings suggest a
      role for MIF in both the homeostatic and physiological action of glucocorticoids
      in vivo.

PMID- 12507890
TI  - Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive
      osteopetrosis.
AB  - Autosomal-recessive osteopetrosis is a severe genetic disease caused by
      osteoclast failure. Approximately 50% of the patients harbor mutations of the
      ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found
      inactivating ATP6i mutations in four patients, and three of these were novel.
      Patients shared macrocephaly, growth retardation and optic nerve alteration,
      osteosclerotic and endobone patterns, and high alkaline phosphatase and
      parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with
      active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)
      positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of
      which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant
      fibrous tissue containing TRAP-positive putative osteoclast precursors were
      noted. In vitro osteoclasts were a3-negative, morphologically normal, with
      prominent clear zones and actin rings, and TRAP activity more elevated than in
      control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were
      unremarkable. Consistent with the finding in the bone biopsies, these cells
      excavated pits faintly stained with toluidine blue, indicating inefficient bone
      resorption. Bone marrow transplantation was successful in all patients, and
      posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.

PMID- 12507891
TI  - Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness
      and differentiation in vitro.
AB  - In epithelial tissue, cell-matrix and cell-cell adhesive interactions have
      important roles in the normal organization and stabilization of the cell layer.
      The malignant conversion of epithelial cells involves alterations in the
      expression and function of these adhesion systems that enable a switch to a
      migratory phenotype in tumor invasion and metastasis. Fascin is an actin
      crosslinking protein that is found in the core actin bundles of cell-surface
      spikes and projections that are implicated in cell motility. We demonstrate that
      fascin is not detectable in normal colonic epithelium, but is dramatically up
      regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could
      participate in tumor invasive behavior, we developed a cell culture model to
      examine the effect of fascin expression on the adhesive interactions,
      invasiveness, and differentiation of colonic epithelial cells. We report marked
      effects on the organization of cell-surface protrusions, actin cytoskeleton, and
      focal adhesions in the absence of alterations in the protein levels of the major
      components of these structures. These effects correlate with alterations in cell
      movements on two-dimensional matrix, and increased invasiveness in three
      dimensional matrix. The cells also show increased proliferation and decreased
      capacity for normal glandular differentiation in collagen gels. We propose that
      up-regulation of fascin, by promoting the formation of protrusive, actin-based,
      cell-motility structures, could be a significant component in the acquisition of
      invasive phenotype in colonic carcinoma.

PMID- 12507892
TI  - A truncated isoform of the protein phosphatase 2A B56gamma regulatory subunit may
      promote genetic instability and cause tumor progression.
AB  - F10, a subline of the B16 mouse melanoma cell line, is itself the parent of the
      more metastatic BL6 line. BL6 cells differ from F10 cells by an alteration of the
      gene encoding the B56gamma regulatory subunit of protein phosphatase 2A (PP2A),
      which results in the expression of a truncated variant of the subunit
      (Deltagamma1). PP2A is involved in regulating the cell-cycle checkpoint and we
      found that the checkpoint in BL6 cells is aberrant when the Deltagamma1 protein
      is expressed. That is, although Deltagamma1 protein levels in cultured BL6 cells
      are low and these cells do not show an altered checkpoint on gamma-irradiation,
      irradiated footpad BL6 tumor cells show both a marked increase in Deltagamma1
      levels and more extensive polyploidy and less apoptosis than F10 cells. These
      observations were reproduced with Deltagamma1 gene-transfected F10 cells
      (F10(Deltagamma1)). Deltagamma1 expression and an aberrant checkpoint are also
      associated with a higher metastatic ability because irradiated F10(Deltagamma1)
      tumors metastasized much more frequently than F10 tumors, which rarely
      metastasized whether irradiated or not. Nonirradiated F10(Deltagamma1) tumors,
      which do not express Deltagamma1 protein, had similarly low rates of metastasis.
      The greater metastatic ability of irradiated F10(Deltagamma1) tumors also
      correlated with the acquisition of many more genomic alterations. Thus, it seems
      that Deltagamma1 expression may damage the checkpoint, which may then allow the
      acquisition of genetic alterations that promote metastasis. These observations
      support the notion that mechanisms promoting the genetic instability of tumors
      could also aid tumor progression from the nonmetastatic to the metastatic state.

PMID- 12507893
TI  - Regulation of EMAP II by hypoxia.
AB  - Endothelial-monocyte-activating polypeptide II (EMAP II) is a proinflammatory
      cytokine and a chemoattractant for monocytes and granulocytes. We have previously
      shown that EMAP II mRNA is strongly expressed at sites of apoptosis in the mouse
      embryo and that the mature protein is cleaved from its cellular precursor
      (proEMAP II/p43) by caspase activation to become released from cells. Here we
      demonstrate in vivo that EMAP II mRNA expression is strongly increased in tumor
      necrosis factor alpha (TNF)-treated murine meth A fibrosarcomas and in B16
      melanomas, especially in close proximity to areas of tissue necrosis.
      Furthermore, by means of confocal microscopy, high level expression of proEMAP
      II/p43 protein correlated predominantly with hypoxic but also with apoptotic
      cells. In vitro, EMAP II mRNA levels were not increased by hypoxia. However, high
      amounts of mature EMAP II protein were detected in the supernatants of hypoxic
      tumor cells. Unlike in apoptotic cells, neither a broad-range caspase inhibitor
      nor an inhibitor specific for the internal cleavage site was able to inhibit
      processing of proEMAP II/p43 to the mature EMAP II protein. In conclusion, these
      data suggest that hypoxia and apoptosis provide two alternative mechanisms of
      EMAP II generation by tumor cells.

PMID- 12507894
TI  - Primary follicular lymphoma of the small intestine: alpha4beta7 expression and
      immunoglobulin configuration suggest an origin from local antigen-experienced B
      cells.
AB  - Primary follicular lymphoma of the gastrointestinal tract (GI-FL) is a rare so
      far poorly studied entity. We analyzed four FL cases located in the small
      intestine and duodenum to gain insight in their pathogenesis and to find an
      explanation for their low tendency to disseminate outside the GI tract. GI-FLs
      resemble nodal FLs with respect to morphology and expression of typical GC
      markers such as CD10, CD38, and BCL-6. We established that the high levels of the
      anti-apoptosis protein BCL-2 in the tumor cells are in all cases due to a
      t(14;18) involving the immunoglobulin heavy chain and BCL-2 loci. Detailed
      immunoglobulin gene analyses on microdissected tissue samples further supported
      the GC-cell derivation: GI-FLs carry extensively mutated variable heavy-chain
      genes. The mutation patterns indicated that at some time point in development
      stringent antigen receptor-based selection processes must have occurred.
      Interestingly, three of four neoplasms expressed surface IgA, an immunoglobulin
      class typical of the mucosal immune system and seldom found in nodal FL. In
      contrast to nodal FLs, the GI-FLs expressed the alpha4beta7 integrin, an
      established mucosa-homing receptor also expressed by normal intestinal B and T
      lymphocytes and by low-grade mucosa-associated lymphoid tissue lymphomas.
      However, the chemokine receptor CXCR3, expressed on low-grade mucosa-associated
      lymphoid tissue lymphomas, was not detected on the GI-FLs or on nodal FLs. The
      combined data suggests that primary FL of the small intestine is a distinct
      entity that originates from local antigen-responsive B cells.

PMID- 12507895
TI  - Trophoblastic oxidative stress in relation to temporal and regional differences
      in maternal placental blood flow in normal and abnormal early pregnancies.
AB  - Onset of the maternal-placental circulation was studied by Doppler
      ultrasonography in 65 pairs of age-matched normal and abnormal pregnancies. In
      normal pregnancies intervillous blood flow increased with gestational age, being
      detected in 9 of 25 cases at 8 to 9 weeks but in 18 of 20 at 12 to 13 weeks (P =
      0.001). By contrast, in abnormal pregnancies flow was detected in nearly all
      cases (22 of 25) at 8 to 9 weeks (P < 0.001). In addition, regional differences
      were observed between the groups. Early flow was restricted to the peripheral
      regions of most normal placentas (P < 0.001), whereas in missed miscarriages it
      was most common in central regions or throughout the placenta (P < 0.05 and P <
      0.001, respectively). Immunoreactivity for heat shock protein 70 and
      nitrotyrosine residues was greater in samples from peripheral than from central
      regions of normal placentas (P = 0.028 and P = 0.019, respectively), and from
      missed miscarriages compared to controls (P = 0.005 and P = 0.001, respectively).
      Our results indicate that oxidative damage to the trophoblast, induced by
      premature and widespread onset of the maternal placental circulation secondary to
      shallow trophoblast invasion, is a key factor in early pregnancy loss. High
      oxygen concentrations in the periphery of normal early placentas may similarly
      induce local regression of the villi, leading to formation of the chorion laeve.

PMID- 12507896
TI  - Do alloreactivity and prolonged cold ischemia cause different elementary lesions
      in chronic allograft nephropathy?
AB  - This study assesses the individual contributions of the nonalloreactive factor,
      cold ischemia (CI), and alloreactivity to late functional and structural renal
      graft changes, and examines the effect of the association of both factors on the
      progression of chronic allograft nephropathy. Lewis rats acted as receptors of
      kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5
      hours. The rats were divided into four groups: Syn, syngeneic graft; SynI,
      syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI.
      Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for
      acute inflammatory response at 1 week and for chronic histological damage at 24
      weeks. Only when CI and allogenicity were combined did immediate posttransplant
      mortality occur, while survivors showed accelerated renal insufficiency that
      induced further mortality at 12 weeks after transplant. Solely ischemic rats
      developed renal insufficiency. Renal structural damage in ischemic rats was
      clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis
      appeared only in the allogeneic groups. There was increased infiltration of
      macrophages and expression of mRNA-transforming growth factor-beta1 in the
      ischemic groups, irrespective of the allogeneic background. The joint association
      of CI plus allogenicity significantly increased cellular infiltration at both
      early and late stages, aggravating tubulointerstitial and vascular damage
      considerably. In summary, CI is mainly responsible for tubulointerstitial damage,
      whereas allogenicity leads to vascular lesion. The association of both factors
      accelerates and aggravates the progression of experimental chronic allograft
      nephropathy.

PMID- 12507897
TI  - Experimental autoimmune encephalomyelitis (EAE) in CCR2(-/-) mice: susceptibility
      in multiple strains.
AB  - Chemokines are low molecular weight cytokines which act as chemoattractants for
      infiltrating cells bearing appropriate receptors (CCR) to sites of inflammation.
      It has been proposed that CCR2 on monocytes is responsible for their recruitment
      into the central nervous system (CNS) in experimental autoimmune
      encephalomyelitis (EAE), a model for multiple sclerosis, and two previous reports
      have described resistance of CCR2(-/-) mice to EAE. The present study examined
      three different mouse strains with CCR2 deletions for susceptibility to EAE.
      Animals were studied up to 4 months post-sensitization and were examined by
      neuropathology, RNase protection assay, in situ hybridization, and in vitro
      assays. All three strains were found to be susceptible to EAE: C57BL/6 x J129 and
      Balb c strains, 100%; and C57BL/6, 67%. Unusual in CNS lesions of CCR2(-/-) mice
      was an overabundance of neutrophils versus monocytes in wild-type animals. An
      attempt of the immune system to develop compensatory mechanisms for the lack of
      CCR2 was evidenced by a corresponding increase in mRNA for other chemokines and
      CCR. Inasmuch as neutrophils replaced monocytes and led to demyelination, our
      findings support the concept that promiscuity of chemokines and CCR was able to
      surmount the deletion of CCR2, still resulting in full expression of this
      autoimmune disease.

PMID- 12507898
TI  - The renin-angiotensin system influences ocular endothelial cell proliferation in
      diabetes: transgenic and interventional studies.
AB  - Neovascularization in the retina and iris of diabetic patients is a major cause
      of severe visual loss. However, study of these lesions is compromised by the lack
      of a comparable diabetic rodent model. Because the vasoactive and angiogenic
      agent, angiotensin II, is involved in diabetic microvascular disease, we aimed to
      determine whether endothelial cell proliferation could be induced in the retinae
      and irides of hypertensive transgenic (mRen-2)27 rats that display an enhanced
      extra-renal renin-angiotensin system (RAS), including the eye. Six-week-old Ren
      2, spontaneously hypertensive, and Sprague-Dawley rats received either
      streptozotocin or control vehicle and were studied for 36 weeks. Additional
      nondiabetic and diabetic Ren-2 rats were treated throughout with the angiotensin
      converting enzyme inhibitor lisinopril (LIS) (10 mg/kg/day in drinking water).
      Endothelial cell proliferation was only observed in retinae and irides of
      diabetic Ren-2 rats and was reduced with LIS. In diabetic Ren-2, vascular
      endothelial growth factor (VEGF) and VEGFR-2 mRNA were increased in retinae and
      irides and reduced with LIS. Diabetes activated ocular renin in Ren-2 but not
      Sprague-Dawley rats. The diabetic Ren-2 rat is a model of intraocular endothelial
      cell proliferation that can be attenuated by RAS blockade via VEGF-dependent
      pathways. RAS blockade is a potential treatment for vision-threatening diabetic
      microvascular complications.

PMID- 12507899
TI  - Role of INK4a/Arf locus-encoded senescent checkpoints activated in normal and
      psoriatic keratinocytes.
AB  - During malignant transformation in skin, epidermal keratinocytes (KCs) frequently
      acquire the capacity to by-pass cellular senescence, a response that normally
      limits their unrestricted proliferation. Despite growing interest in the role for
      senescence during aging of skin and cutaneous carcinogenesis, little is known
      regarding regulation of three proteins encoded by the INK4a/ARF locus (p12,
      p14(ARF), p16) in KCs. In this study, several molecular pathways are explored
      using cultured KCs and KCs freshly isolated from psoriatic plaques. p16 and
      p14(ARF) are predominantly expressed spontaneously when foreskin-derived early
      passage KCs undergo confluency-induced premature senescence. Induction of
      p14(ARF) on confluency occurred with low E2F-1 levels. Suspension of KCs in
      methylcellulose induced p12 expression. Addition of various cytokines (interferon
      gamma, tumor necrosis factor-alpha) or a phorbol ester [12-O-tetradecanoylphorbol
      13-acetate (TPA)] only induced p16, but not p14(ARF). Confluent KCs up-regulated
      Ras activity and the downstream signaling involving ERK. Addition of MAPK
      inhibitor blocked cytokine and TPA-induced p16 expression. Confluency and
      interferon-gamma induced premature senescence and p16 expression was linked to
      induction of the transcription factor Egr-1. KCs derived from chronic psoriatic
      plaques were characterized by enhanced p16, p14(ARF), and p12 expression
      accompanied by elevated Egr-1 levels. These results demonstrate that multiple and
      highly divergent stimuli can trigger the senescent checkpoint in human KCs with
      differential regulation of p16, p14(ARF), and p12. Although abnormal mitogenic
      signaling by oncogenic Ras is generally cited as being responsible for induction
      of premature senescence, our findings indicate that a broader perspective is
      warranted, to include confluency and cytokine-/TPA-induced pathways for KCs.

PMID- 12507900
TI  - Vascular endothelial growth factor isoforms and their receptors are expressed in
      human osteoarthritic cartilage.
AB  - To assess the possible involvement of vascular endothelial growth factor (VEGF)
      in the pathology of osteoarthritic (OA) cartilage, we examined the expression of
      VEGF isoforms and their receptors in the articular cartilage, and the effects of
      VEGF on the production of matrix metalloproteinases (MMPs) and tissue inhibitors
      of metalloproteinases (TIMPs) in OA chondrocytes. Reverse transcriptase
      polymerase chain reaction analyses demonstrated that mRNAs for three VEGF
      isoforms (VEGF(121), VEGF(165), and VEGF(189)) are detectable in all of the OA
      and normal (NOR) cartilage samples. However, the mRNA expression of their
      receptors (VEGFR-1 = Flt-1, VEGFR-2 = KDR and neuropilin-1) was recognized only
      in the OA samples. The protein expression of VEGFR-1 and VEGFR-2 in OA
      chondrocytes was also demonstrated by immunohistochemistry of the OA cartilage
      tissue and cultured OA chondrocytes. In situ hybridization and
      immunohistochemistry indicated that VEGF is expressed in the chondrocytes in the
      superficial and transitional zones of OA cartilage. A linear correlation was
      obtained between VEGF immunoreactivity and Mankin scores in the cartilage (r =
      0.906, P < 0.001). The production levels of VEGF determined by enzyme-linked
      immunosorbent assay were significantly 3.3-fold higher in OA than in NOR samples
      (P < 0.001). Among MMP-1, -2, -3, -7, -8, -9, and -13, TIMP-1 and -2 measured by
      their sandwich enzyme immunoassay systems, the production of MMP-1 and MMP-3 but
      not TIMP-1 or TIMP-2 was significantly enhanced by the treatment of cultured OA
      chondrocytes with VEGF (P < 0.05), whereas no such effect was obtained with
      cultured NOR chondrocytes. These results demonstrate that VEGF and its receptors
      are expressed in OA cartilage, and suggest the possibility that VEGF is
      implicated for the destruction of OA articular cartilage through the increased
      production of MMPs.

PMID- 12507901
TI  - Tumor vessel development and maturation impose limits on the effectiveness of
      anti-vascular therapy.
AB  - The effect of anti-vascular agents on the growth of experimental tumors is well
      studied. Their impact on tumor vasculature, the primary therapeutic target of
      these agents, is not as well characterized, even though this primarily determines
      treatment outcome. Hypothesizing that the response of vessels to therapy is
      influenced by their stage of maturation, we studied vascular development and the
      vascular effects of therapy in several transplanted murine tumor models. Based on
      size, perfusion, endothelial cell (EC) proliferation, and the presence of
      pericytes, tumor vessels segregated into three categories. Least mature were
      highly proliferative, nonperfused EC sprouts emanating from functional vessels.
      Intermediate were small, perfused vessels which, like the angiogenic sprouts,
      were not covered by pericytes. Most mature were larger vessels, which were
      predominantly pericyte-covered with quiescent ECs and few associated sprouts.
      Thus, a developmental order, similar to that described during physiological
      neovascularization, was evident among vessels in growing tumors. This order
      markedly influenced tumor vessel response to anti-vascular therapy with
      recombinant interleukin-12. Therapy reduced tumor vessel density, which was
      attributable to a decrease in angiogenic sprouts and induction of EC apoptosis in
      pericyte-negative vessels. Although the great majority of vessels in growing
      tumors lacked pericyte coverage, selective loss of less mature vessels with
      therapy significantly increased the fraction of pericyte-positive vessels after
      therapy. These data indicate that the therapeutic susceptibility of tumor
      vasculature to recombinant murine IL-12 and, potentially, other anti-vascular
      agents is limited by its level of maturation. An implication is that tumor
      susceptibility is similarly limited, making pericyte coverage of tumor
      vasculature a potential indicator of tumor responsiveness.

PMID- 12507902
TI  - Hepatic microenvironment affects oval cell localization in albumin-urokinase-type
      plasminogen activator transgenic mice.
AB  - Mice carrying an albumin-urokinase type plasminogen activator transgene (AL-uPA)
      develop liver disease secondary to uPA expression in hepatocytes. Transgene
      expressing parenchyma is replaced gradually by clones of cells that have deleted
      transgene DNA and therefore are not subject to uPA-mediated damage. Diseased
      liver displays several abnormalities, including hepatocyte vacuolation and
      changes in nonparenchymal tissue. The latter includes increases in laminin
      protein within parenchyma and the appearance of cytokeratin 19-positive bile
      ductule-like cells (oval cells) both in portal regions and extending into the
      hepatic parenchyma. In this study, we subjected AL-uPA mice to two-thirds partial
      hepatectomy to identify the response of these livers to additional growth
      stimulation. We observed several changes in hepatic morphology. First, the oval
      cells increased in number and often formed ductules in the parenchyma. Second,
      this cellular change was accompanied by a further increase in laminin associated
      with single or clusters of oval cells. Third, desmin-positive Ito cells increased
      in number and maintained close association with oval cells. Fourth, these changes
      were localized precisely to uPA-expressing areas of liver. Regenerating clones of
      uPA-deficient cells appeared to be unaffected both by stromal and cellular
      alterations. Thus, additional growth stimulation of diseased uPA-expressing liver
      induces an oval cell-like response, as observed in other models of severe hepatic
      injury, but the localization of this response seems to be highly regulated by the
      hepatic microenvironment.

PMID- 12507903
TI  - Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide
      synthase activity as a molecular mechanism for keratinocyte hyperproliferation.
AB  - Abnormal proliferation of keratinocytes in the skin appears crucial to the
      pathogenesis of psoriasis, but the underlying mechanisms remain unknown. Nitric
      oxide (NO), released from keratinocytes at high concentrations, is considered a
      key inhibitor of cellular proliferation and inducer of differentiation in vitro.
      Although high-output NO synthesis is suggested by the expression of inducible NO
      synthase (iNOS) mRNA and protein in psoriasis lesions, the pronounced
      hyperproliferation of psoriatic keratinocytes may indicate that iNOS activity is
      too low to effectively deliver anti-proliferative NO concentrations. Here we show
      that arginase 1 (ARG1), which substantially participates in the regulation of
      iNOS activity by competing for the common substrate L-arginine, is highly
      overexpressed in the hyperproliferative psoriatic epidermis and is co-expressed
      with iNOS. Expression of L-arginine transporter molecules is found to be normal.
      Treatment of primary cultured keratinocytes with Th1-cytokines, as present in a
      psoriatic environment, leads to de novo expression of iNOS but concomitantly a
      significant down-regulation of ARG1. Persistent ARG1 overexpression in psoriasis
      lesions, therefore, may represent a disease-associated deviation from normal
      expression patterns. Furthermore, the culturing of activated keratinocytes in the
      presence of an ARG inhibitor results in a twofold increase in nitrite
      accumulation providing evidence for an L-arginine substrate competition in human
      keratinocytes. High-output NO synthesis is indeed associated with a significant
      decrease in cellular proliferation as shown by down-regulation of Ki67 expression
      in cultured keratinocytes but also in short-term organ cultures of normal human
      skin. In summary, our data demonstrate for the first time a link between a human
      inflammatory skin disease, limited iNOS activity, and ARG1 overexpression. This
      link may have substantial implications for the pathophysiology of psoriasis and
      the development of new treatment strategies.

PMID- 12507904
TI  - Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing
      the human tau isoform with the P301L mutation.
AB  - We recently reported a transgenic mouse line (JNPL3) that expresses mutant
      (P301L) tau and develops neurofibrillary tangles composed of filamentous tau
      aggregates. Here we show that these mice have abnormal tau filaments not only in
      neurons, but also in oligodendrocytes and astrocytes. Similar results were
      detected in another transgenic line (JNPL2+3+) that expresses the longest human
      tau isoform with the P301L mutation. The ultrastructure of the tau filaments and
      immunoreactivity with tau and ubiquitin antibodies were similar in glia and
      neurons. Given similarities of the lesions in the mice to human neuronal and
      glial inclusions, these transgenic mice appear to be a valuable model to study
      pathogenesis of the neurodegenerative tauopathies.

PMID- 12507905
TI  - CCN5 is a growth arrest-specific gene that regulates smooth muscle cell
      proliferation and motility.
AB  - Vascular smooth muscle cell (VSMC) hyperplasia plays an important role in both
      chronic and acute vascular pathologies. Considerable work has focused on the
      mechanisms regulating VSMC growth and the search for agents that could suppress
      VSMC hyperproliferation. One of the several inhibitors studied is the
      glycosaminoglycan heparin, which inhibits VSMC proliferation and migration both
      in cell culture and in animal models (Mishra-Gorur K, Delmolino LM, Castellot Jr
      JJ: Biological functions of heparan sulfate and heparan sulfate proteoglycans.
      Trends Glycosci Glycotechnol 1998, 10:193-210). To aid our understanding of the
      anti-proliferative mechanism of action of heparin, we used a subtractive
      hybridization approach to isolate and characterize a novel growth arrest-specific
      (gas) gene induced in VSMCs exposed to heparin (Delmolino LM, Stearns NA,
      Castellot Jr JJ: Heparin induces a member of the CCN family which has
      characteristics of a growth arrest specific gene. Mol Biol Cell 1997, 8:287a and
      Delmolino LM, Stearns NA, Castellot Jr JJ: COP-1, a member of the CCN family, is
      a heparin-induced growth arrest specific gene in vascular smooth muscle cells. J
      Cell Physiol 2001, 188:45-55). This gene is a member of the cysteine-rich
      61/connective tissue growth factor/nephroblastoma-overexpressed (CCN) family and
      has been given the name CCN5. In this report, we provide functional evidence that
      CCN5 can inhibit VSMC proliferation, motility, and invasiveness. In contrast,
      adhesion and apoptosis are unaffected by CCN5 in this cell type. We also
      significantly extend previous data from our laboratory that suggests CCN5 is a
      growth arrest-specific (gas) gene. Furthermore, we map for the first time the
      cellular localization of CCN5 protein in cultured VSMCs. We also examine
      uninjured and balloon-injured rat carotid arteries for CCN5 expression. The
      results from the in vitro and in vivo localization studies show that CCN5 is
      temporally and spatially expressed in a manner consistent with a role in
      regulating proliferation, motility, and invasiveness of VSMCs.

PMID- 12507906
TI  - The transcriptional co-activator cAMP response element-binding protein-binding
      protein is expressed in prostate cancer and enhances androgen- and anti-androgen
      induced androgen receptor function.
AB  - Progression of human prostate cancer toward therapy resistance occurs in the
      presence of wild-type or mutated androgen receptors (ARs) that, in some cases,
      exhibit aberrant activation by various steroid hormones and anti-androgens. The
      AR associates with a number of co-activators that possess histone acetylase
      activity and act as bridging molecules to components of the transcription
      initiation complex. In previous reports, it was shown that the transcriptional co
      activator CREB (cAMP response element-binding protein)-binding protein (CBP)
      enhances AR activity in a ligand-dependent manner. In the present study, we have
      investigated whether CBP modifies antagonist/agonist balance of the nonsteroidal
      anti-androgens hydroxyflutamide and bicalutamide. In prostate cancer DU-145
      cells, which were transiently transfected with CBP cDNA, hydroxyflutamide
      enhanced AR activity to a greater extent than bicalutamide in the presence of
      either wild-type or the mutated AR 730 val-->met. In two sublines of LNCaP cells
      that contain the mutated AR 877 thr-->ala and overexpressed CBP, increase in AR
      activity was observed after treatment with hydroxyflutamide but not with
      bicalutamide. Anti-androgens did not influence AR expression in cells transfected
      with CBP cDNA, as judged by Western blot analysis. Endogenous CBP protein was
      detected by Western blot in nuclear extracts from the three prostate cancer cell
      lines, LNCaP, PC-3, and DU-145, all derived from therapy-resistant prostate
      cancer. In addition, CBP was expressed in both basal and secretory cells of
      benign prostate epithelium, high-grade prostate intraepithelial neoplasia, and
      prostate cancer clinical specimens, as evidenced by immunohistochemical staining.
      Taken together, our findings demonstrate the selective enhancement of agonistic
      action of the anti-androgen hydroxyflutamide by the transcriptional co-activator
      CBP, which is a new, potentially relevant mechanism contributing to the
      acquisition of therapy resistance in prostate cancer.

PMID- 12507908
TI  - Dysregulation of the annexin family protein family is associated with prostate
      cancer progression.
AB  - Hormone refractory prostate cancer (PCa) is invariably lethal despite aggressive
      clinical treatment strategies. Detection strategies are needed to identify
      aggressive PCa before it becomes widely disseminated. Recently, two studies
      identified annexin 1 and 7 as potential biomarkers in the development of PCa
      progression. The annexins are a group of calcium-binding structural proteins that
      may play a role in the regulation of membrane trafficking, cellular adhesion, and
      cell signaling. Therefore the goal of this study is to simultaneously
      characterize the multiple members of the annexin family of genes in advanced PCa.
      Prostate samples from men with advanced hormone refractory PCa were compared to
      samples of hormone-naive PCa and noncancerous prostate tissue. Samples from 15
      patients with advanced hormone refractory PCa were used. To examine the annexin
      family, gene expression profiles from 21 noncancerous prostate tissues, 16
      clinically localized PCas, and 20 hormone refractory PCa samples were used. By
      cDNA microarray analysis, annexins 1, 2, 4, 7, and 11 were significantly
      decreased in hormone refractory PCa when compared to localized hormone-naive PCa
      with 2.2-, 1.5-, 1.3-, 1.4-, and 1.8-fold decreases, respectively (all P values
      <0.05). Interstudy validation of annexin family transcript expression was
      performed by meta-analysis of three other published prostate profiling studies.
      High-density tissue microarrays were used to validate a subset of annexins at the
      protein level by immunohistochemistry. Tissue microarray analysis revealed a
      significant decrease in protein expression for annexins 1, 2, 4, 7, and 11 in
      hormone refractory PCa as compared to localized PCa with 1.68-, 2.46-, 2.52-, and
      3.01-fold decreases, respectively (Kruskal Wallis test, all P values P < 0.05).
      However, no significant differences were detected between the clinically
      localized PCa and noncancerous prostate tissues. These findings suggest that down
      regulation of several members of the annexin family may contribute to PCa
      tumorigenesis. Annexins 1, 2, 4, 7, and 11 may play a role in tumor progression
      through distinct mechanisms or, alternatively, they may have redundant tumor
      suppressor activities. This study also suggests that a meta-analysis of existing
      gene expression data is useful in confirming findings from individual studies.
      Finally, down-regulation of several annexin family members may play a role in the
      development of the lethal PCa phenotype.

PMID- 12507907
TI  - Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and
      consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the
      absence of immunoglobulins.
AB  - Although primary mediastinal (thymic) large B-cell lymphoma has been primarily
      studied, its precise phenotype, molecular characteristics, and histogenesis are
      still a matter of debate. The International Extranodal Lymphoma Study Group
      collected 137 such cases for extensive pathological review. Histologically, the
      lymphomatous growth was predominantly diffuse with fibrosis that induced
      compartmentalized cell aggregation. It consisted of large cells with varying
      degrees of nuclear polymorphism and clear to basophilic cytoplasm. On
      immunohistochemistry, the following phenotype was observed: CD45(+), CD20(+),
      CD79a(+), PAX5/BSAP(+), BOB.1(+), Oct-2(+), PU.1(+), Bcl-2(+), CD30(+), HLA
      DR(+), MAL protein(+/-), Bcl-6(+/-), MUM1/IRF4(+/-), CD10(-/+), CD21(-), CD15(-),
      CD138(-), CD68(-), and CD3(-). Immunoglobulins were negative both at
      immunohistochemistry and in situ hybridization. Molecular analysis, performed in
      45 cases, showed novel findings. More than half of the cases displayed BCL-6 gene
      mutations, which usually occurred along with functioning somatic IgV(H) gene
      mutations and Bcl-6 and/or MUM1/IRF4 expression. The present study supports the
      concept that a sizable fraction of cases of this lymphoma are from activated
      germinal center or postgerminal center cells. However, it differs from other
      aggressive B-cell lymphomas in that it shows defective immunoglobulin production
      despite the expression of OCT-2, BOB.1, and PU.1 transcription factors and the
      lack of IgV(H) gene crippling mutations.

PMID- 12507909
TI  - Development of colitis in signal transducers and activators of transcription 6
      deficient T-cell receptor alpha-deficient mice: a potential role of signal
      transducers and activators of transcription 6-independent interleukin-4 signaling
      for the generation of Th2-biased pathological CD4+ betabetaT cells.
AB  - Forbidden CD4(+)betabeta T cells, which produce interleukin (IL)-4 predominantly,
      are a pathological subset in the development of colitis in T-cell receptor alpha
      chain (TCRalpha)-deficient mice. Stimulation of naive CD4(+) T cells with IL-4
      induces Th2 development via the activation of signal transducers and activators
      of transcription (STAT) 6. In the present study, we had found that IL-4 enhanced
      the expression of STAT6 in CD4(+)betabeta T cells isolated from TCRalpha(-/-)
      mice with colitis, suggesting that the IL-4 signal in the CD4(+)betabeta T cells
      is mediated by STAT6. To further investigate the role of STAT6 in the development
      of colitis induced by TCRalpha deficiency, we generated double-deficient mice by
      crossing TCRalpha(-/-) mice and STAT6(-/-) mice. Surprisingly, STAT6 deficiency
      did not result in decreased severity of colitis in TCRalpha(-/-) mice. STAT6
      deficient CD4(+)betabeta T cells produced IL-4 and intraperitoneal injection of
      anti-IL-4 monoclonal antibody in the nondiseased TCRalpha(-/-) and STAT6 double
      deficient mice prevented the colitis formation, thus indicating that the cells
      differentiated into the Th2 phenotype have the ability to mediate the development
      of the colitis in the absence of STAT6.

PMID- 12507910
TI  - Endocytic pathway alterations in human hippocampus after global ischemia and the
      influence of APOE genotype.
AB  - Apolipoprotein epsilon4 (apoE, protein; APOE, gene) allele is the most important
      genetic risk factor for development of Alzheimer's disease and is also associated
      with poor outcome after brain injury. Although the mechanisms underlying this
      susceptibility are currently unknown, recent experimental evidence suggests that
      APOE genotype may influence activity in the endocytic pathway of neurons. This
      study determined whether alterations in the endocytic pathway occurred in medial
      temporal lobe sections after brain injury because of cardiorespiratory arrest and
      whether these alterations were influenced by APOE genotype. Antibodies to two
      proteins involved in endocytosis, rabaptin-5 and rab4, were used as markers of
      endocytic pathway activity. Alterations in immunoreactivity were examined in
      medial temporal lobe sections in the postmortem brain of patients who experienced
      an episode of global ischemia and in controls. After global ischemia there was a
      marked increase in immunoreactivity of both endocytic markers, rabaptin-5 and
      rab4, in neurons, and to a lesser extent in glia compared to controls.
      Furthermore, possession of an APOE epsilon4 allele was associated with specific
      alterations in the endocytic pathway. After global ischemia, there was no
      influence of APOE genotype on the extent of rabaptin-5 immunoreactivity. However,
      there was a statistically significant influence of APOE genotype on the extent of
      rab4 immunoreactivity in response to global ischemia. These results indicate
      marked alterations in the endocytic pathway after global ischemia that are
      dependent on APOE genotype. This may underlie the important influence of APOE
      genotype on brain injury and disease.

PMID- 12507911
TI  - Experimental glomerulopathy alters renal cortical cholesterol, SR-B1, ABCA1, and
      HMG CoA reductase expression.
AB  - Previous studies indicate that acute tubular injury causes free cholesterol (FC)
      and cholesteryl ester (CE) accumulation within renal cortex/proximal tubules.
      This study assessed whether similar changes occur with glomerulopathy/nephrotic
      syndrome, in which high-circulating/filtered lipoprotein levels increase renal
      cholesterol supply. Potential adaptive changes in cholesterol synthetic/transport
      proteins were also assessed. Nephrotoxic serum (NTS) or passive Heymann nephritis
      (PHN) was induced in Sprague-Dawley rats. Renal injury (blood urea nitrogen,
      proteinuria) was assessed 2 and 7 days (NTS), or 10 and 30 days (PHN) later. FC
      and CE levels in renal cortex, isolated glomeruli, and proximal tubule segments
      were determined. SR-B1 (a CE influx protein), ABCA1 (a FC exporter), and HMG CoA
      reductase protein/mRNA levels were also assessed. FC was minimally elevated in
      renal cortex (0 to 15%), the majority apparently localizing to proximal tubules.
      More dramatic CE elevations were found ( approximately 5 to 15x), correlating
      with the severity of proteinuria at any single time point (r >/= 0.85).
      Cholesterol increments were associated with decreased SR-B1, increased ABCA1, and
      increased HMG CoA reductase (HMGCR) protein and its mRNA. Tubule (HK-2) cell
      culture data indicated that SR-B1 and ABCA1 levels are responsive to cholesterol
      supply. Experimental nephropathy can increase renal FC, and particularly CE,
      levels, most notably in proximal tubules. These changes are associated with
      adaptations in SR-B1 and ABCA1 expression, which are physiologically appropriate
      changes for a cholesterol overload state. However, HMGCR protein/mRNA increments
      can also result. These seem to reflect a maladaptive response, potentially
      contributing to a cell cholesterol overload state.

PMID- 12507912
TI  - Interleukin-10 inhibits elevated chemokine interleukin-8 and regulated on
      activation normal T cell expressed and secreted production in cystic fibrosis
      bronchial epithelial cells by targeting the I(k)B kinase alpha/beta complex.
AB  - Accumulating evidence suggests that in cystic fibrosis (CF) patients, airway
      fluids are characterized by decreased antibacterial activity, elevated NaCl
      concentration, and high levels of chemokines, resulting in exaggerated activation
      of the transcriptional nuclear factor (NF)-kappaB in airway epithelial cells. The
      present study was undertaken to evaluate the effects of anti-inflammatory
      cytokine interleukin-10 (IL-10) on NaCl-induced chemokine IL-8 and regulated on
      activation normal T cell expressed and secreted (RANTES) expression through the
      NF-kappaB signaling in primary deltaF508 CF and non-CF (control) human bronchial
      epithelial cells. Exposure of CF and non-CF bronchial epithelial cells to
      hypertonic (170 mmol/L NaCl) milieu compared to isotonic (115 mmol/L NaCl) and
      hypotonic (85 mmol/L NaCl) milieu caused a significant, NaCl-dependent increase
      in IL-8 and RANTES gene expression and protein production. Compared to non-CF
      cells, CF bronchial epithelial cells were characterized by a higher
      susceptibility to produce elevated IL-8 and RANTES production in an hypertonic
      NaCl milieu in response to IL-1beta activation. Treatment with IL-10 suppressed
      IL-8 and RANTES gene expression in both non-CF and CF bronchial epithelial cells
      was associated with a reduced expression of I(k)B (IKK) alpha/beta kinases,
      particularly for IKKalpha which is greater expressed in CF bronchial epithelial
      cells, and resulting in reduced NF-kappaB activation. These findings suggest that
      IL-10 might have anti-inflammatory benefits in airways of CF patients.

PMID- 12507913
TI  - Cellular dysfunction in the diabetic fibroblast: impairment in migration,
      vascular endothelial growth factor production, and response to hypoxia.
AB  - Although it is known that systemic diseases such as diabetes result in impaired
      wound healing, the mechanism for this impairment is not understood. Because
      fibroblasts are essential for wound repair, we compared the in vitro behavior of
      fibroblasts cultured from diabetic, leptin receptor-deficient (db/db) mice with
      wild-type fibroblasts from mice of the same genetic background in processes
      important during tissue repair. Adult diabetic mouse fibroblast migration
      exhibited a 75% reduction in migration compared to normal fibroblasts (P < 0.001)
      and was not significantly stimulated by hypoxia (1% O(2)), whereas wild-type
      fibroblast migration was up-regulated nearly twofold in hypoxic conditions (P <
      0.05). Diabetic fibroblasts produced twice the amount of pro-matrix
      metalloproteinase-9 as normal fibroblasts, as measured by both gelatin zymography
      and enzyme-linked immunosorbent assay (P < 0.05). Adult diabetic fibroblasts
      exhibited a sevenfold impairment in vascular endothelial growth factor (VEGF)
      production (4.5 +/- 1.3 pg/ml versus 34.8 +/- 3.3 pg/ml, P < 0.001) compared to
      wild-type fibroblasts. Moreover, wild-type fibroblast production of VEGF
      increased threefold in response to hypoxia, whereas diabetic fibroblast
      production of VEGF was not up-regulated in hypoxic conditions (P < 0.001). To
      address the question whether these differences resulted from chronic
      hyperglycemia or absence of the leptin receptor, fibroblasts were harvested from
      newborn db/db mice before the onset of diabetes (4 to 5 weeks old). These
      fibroblasts showed no impairments in VEGF production under basal or hypoxic
      conditions, confirming that the results from db/db fibroblasts in mature mice
      resulted from the diabetic state and were not because of alterations in the
      leptin-leptin receptor axis. Markers of cellular viability including
      proliferation and senescence were not significantly different between diabetic
      and wild-type fibroblasts. We conclude that, in vitro, diabetic fibroblasts show
      selective impairments in discrete cellular processes critical for tissue repair
      including cellular migration, VEGF production, and the response to hypoxia. The
      VEGF abnormalities developed concurrently with the onset of hyperglycemia and
      were not seen in normoglycemic, leptin receptor-deficient db/db mice. These
      observations support a role for fibroblast dysfunction in the impaired wound
      healing observed in human diabetics, and also suggest a mechanism for the poor
      clinical outcomes that occur after ischemic injury in diabetic patients.

PMID- 12507914
TI  - Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is
      associated with the apolipoprotein E-epsilon4 allele.
AB  - Abeta is the major component of amyloid plaques characterizing Alzheimer's
      disease (AD). Abeta accumulation can be affected by numerous factors including
      increased rates of production and/or impaired clearance. Insulin-degrading enzyme
      (IDE) has been implicated as a candidate enzyme responsible for the degradation
      and clearance of Abeta in the brain. We have previously shown that AD patients
      exhibit abnormalities in insulin metabolism that are associated with apoliprotein
      E (APOE) status. The possible association of IDE with AD, as well as the link
      between APOE status and insulin metabolism, led us to examine the expression of
      IDE in AD. We report that hippocampal IDE protein is reduced by approximately 50%
      in epsilon4+ AD patients compared to epsilon4- patients and controls. The allele
      specific decrease of IDE in epsilon4+ AD patients is not associated with neuronal
      loss since neuron-specific enolase levels were comparable between the AD groups,
      regardless of APOE status. Hippocampal IDE mRNA levels were also reduced in AD
      patients with the epsilon4 allele compared to AD and normal subjects without the
      epsilon4 allele. These findings show that reduced IDE expression is associated
      with a significant risk factor for AD and suggest that IDE may interact with APOE
      status to affect Abeta metabolism.

PMID- 12507915
TI  - Tissue-specific inactivation of murine M6P/IGF2R.
AB  - The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes
      a multifunctional protein involved in lysosomal enzyme trafficking, fetal
      organogenesis, tumor suppression, and T cell- mediated immunity. M6P/IGF2R is an
      imprinted gene in mice with expression only from the maternal allele. Complete
      knockout of this gene causes neonatal lethality, thus preventing analysis of its
      multifunctional role postnatally. To help elucidate the biological functions of
      M6P/IGF2R in adulthood, we generated both complete and tissue-specific M6P/IGF2R
      knockout mice using the Cre/loxP system. We confirm that complete M6P/IGF2R
      knockout results in fetal overgrowth and neonatal lethality. In contrast, tissue
      specific inactivation of this gene in either the liver or skeletal and cardiac
      muscle gives rise to viable animals with no obvious phenotype. The successful
      creation of viable tissue-specific M6P/IGF2R knockout mouse models will now allow
      for detailed analysis of receptor function in a number of cellular processes
      including brain development, carcinogenesis, lysosomal trafficking, and T cell
      mediated immunity.

PMID- 12507916
TI  - Transgenic mice expressing mutant Notch3 develop vascular alterations
      characteristic of cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an increasingly recognized adult-onset autosomal
      dominant vascular dementia, caused by highly stereotyped mutations in the Notch3
      receptor. CADASIL is a widespread angiopathy characterized by a degeneration of
      vascular smooth muscle cells (VSMCs) and the abnormal accumulation of electron
      dense granular material called GOM and Notch3 protein, because of an impaired
      clearance. Evidence that VSMCs are the primary target of the pathogenic process
      is supported by the restricted expression of Notch3 in these cells but mechanisms
      of their degeneration remain essentially unknown. We generated transgenic mice in
      which the SM22alpha promoter drove, in VSMCs, the expression of a full-length
      human Notch3 carrying the Arg90Cys mutation, a CADASIL archetypal mutation.
      Transgenic mice showed no evidence of prominent brain parenchyma damage but
      demonstrated the two hallmarks of the CADASIL angiopathy, GOM deposits and Notch3
      accumulation, within both the cerebral and peripheral arteries. Of interest,
      arteries of the tail were more severely affected with prominent signs of VSMC
      degeneration. Time-course analysis of vessel changes revealed that disruption of
      normal VSMC anchorage to adjacent extracellular matrix and cells, VSMC
      cytoskeleton changes as well as starting signs of VSMC degeneration, which were
      detected around 10 months of age, preceded Notch3 and GOM accumulation
      appearance, which were observed only by 14 to 16 months of age. In conclusion, we
      have generated transgenic mice that recapitulate the characteristic vascular
      lesions observed in CADASIL. Our results indicate that Notch3 or GOM accumulation
      are unlikely to be the prerequisites for the induction of VSMC degeneration and
      suggest that degeneration of VSMCs may rather be triggered by the disruption of
      their normal anchorage, based on the important role of adhesion for cell
      survival.

PMID- 12507917
TI  - Null mutation of DNA strand break-binding molecule poly(ADP-ribose) polymerase
      causes medulloblastomas in p53(-/-) mice.
AB  - Medulloblastoma is an invasive embryonal tumor of the cerebellum with predominant
      neuronal differentiation. Although several genes have been implicated in
      medulloblasoma formation, such as Patched (Ptc1) and the adenomatous polyposis
      coli gene (Apc), the majority of these tumors cannot be explained by mutations in
      these genes. The cellular origin as well as the genetic and molecular changes
      involved in the genesis and progression of human medulloblastomas remain largely
      unknown. Here we show that disruption of poly(ADP-ribose) polymerase (PARP-1)
      causes a high incidence (49%) of aggressive brain tumors in p53 null mice, with
      typical features of human cerebellar medulloblastomas. At as early as 8 weeks of
      age, lesions started on the outer surface of the cerebellum from remnant granule
      cell precursors of the developmental external germinal layer. Progression of
      these tumors is associated with the re-activation of the neuronal specific
      transcription factor Math1, dysregulation of Shh/Ptc1 signaling pathway, and
      chromosomal aberrations, including triradial and quadriradial chromosomes. The
      present study indicates that the loss of function of DNA double-strand break
      sensing and repair molecules is an etiological factor in the evolution of the
      cerebellar medulloblastomas. These PARP-1/p53 double null mice represent a novel
      model for the pathogenesis of human medulloblastomas.

PMID- 12507918
TI  - Clonal origin and expansions in neoplasms: biologic and technical aspects must be
      considered together.

PMID- 12507919
TI  - Interleukin-3 receptors in Hodgkin's disease.

PMID- 12507920
TI  - CYP1A1 and GSTM1 genotypes affect benzo[a]pyrene DNA adducts in smokers' lung:
      comparison with aromatic/hydrophobic adduct formation.
AB  - Benzo[a]pyrene diol epoxide (BPDE)-DNA adducts are involved in the induction of
      p53 mutations and probably in the causation of human lung cancer associated with
      cigarette smoking. The ratio between CYP1A1 and GST enzyme activities is a
      critical determinant of the target dose of carcinogenic BPDE and other DNA
      reactive PAH metabolites. In this review, we summarize the published data on
      modulation of (+)-anti-BPDE-DNA adduct levels in smokers' lungs by CYP1A1*2
      genotypes alone or in combination with GSTM1 polymorphism and compare these
      results with those reported for aromatic/hydrophobic (bulky) DNA adducts. The
      data published so far show only a trend for a non-significant increase in bulky
      DNA adduct levels in subjects with GSTM1*0 or the CYP1A1*2-GSTM1*0 genotype
      combination. In contrast, a clear dependence of (+)-anti-BPDE-DNA adduct levels
      was found as a function of the CYP1A1 and GSTM1 genotypes: In lung parenchyma,
      this adduct was more pronounced in persons with the GSTM1*0 genotype, and
      CYP1A1*2-GSTM1*0 carriers had higher (+)-anti-BPDE-DNA adduct levels than those
      with CYP1A1*1/*1-GSTM1*0. The homozygous CYP1A1*2/*2 carriers in the GSTM1*0
      group had the highest (+)-anti-BPDE-DNA adduct levels. Our analysis leads to the
      conclusion that the risk-modifying effects of metabolic genotypes and of gene
      interactions might be more easily identifiable if specific markers of
      structurally defined adducts were used, such as the (+)-anti-BPDE-DNA adduct.
      These results are also consistent with the hypothesis that BP (PAH) induce G:C to
      T:A transversion mutations in the hotspot codons of the p53 tumor suppressor gene
      and are thus involved in malignant transformation of the lung tissue of smokers.

PMID- 12507921
TI  - Smoking-related DNA and protein adducts in human tissues.
AB  - Tobacco smoking causes not only lung cancer but also cancer of the oral and nasal
      cavities, oesophagus, larynx, pharynx, pancreas, liver, kidney, stomach, urinary
      tract and cervix. Tobacco smoke contains many carcinogens that exert their
      biological effects through interaction of reactive intermediates with DNA to form
      DNA adducts. The same electrophilic species also react with cellular proteins.
      The effects of smoking are evident by the detection of elevated levels of
      carcinogen-DNA adducts in many human tissues and of carcinogen-protein adducts in
      blood. Components of tobacco smoke also induce oxidative DNA damage. Systemic
      exposure to tobacco-derived carcinogens is demonstrated by the observation of
      elevated levels of DNA adducts in tissues not directly exposed to tobacco smoke.
      For many of these tissues there is epidemiological evidence, varying from
      comprehensive to preliminary, that smoking is a causative factor in cancer of
      that site. The effects of passive smoking, which also causes lung cancer in non
      smokers, is also evident in elevated levels of protein adducts in exposed non
      smokers so exposed, relative to non-exposed non-smokers. This paper reviews the
      literature on smoking-related DNA and protein adducts in human tissues and shows
      how such studies have provided mechanistic insight into the epidemiological
      associations between smoking and cancer.

PMID- 12507922
TI  - High accumulation of oxidative DNA damage, 8-hydroxyguanine, in Mmh/Ogg1
      deficient mice by chronic oxidative stress.
AB  - 8-Hydroxyguanine (8-OH-G) is a major pre-mutagenic lesion generated from reactive
      oxygen species. The Mmh/Ogg1 gene product plays a major role in maintaining
      genetic integrity by removing 8-OH-G by way of the base excision repair pathway.
      To investigate how oxidative stress influences the formation of 8-OH-G in Ogg1
      mutant mice, a known oxidative agent, potassium bromate (KBrO(3)), was
      administered at a dose of 2 g/l in the drinking water to Ogg1(+/+), Ogg1(+/-) and
      Ogg1(-/-) mice for 12 weeks. Apurinic (AP) site lyase activity, measured by the
      excision of 8-OH-G from synthetic oligonucleotides, remained unchanged in kidney
      cell extracts isolated from Ogg1 mutant mice when the mice were pre-treated by
      KBrO(3). The levels of 8-OH-G in kidney DNA tremendously increased in a time
      dependent manner following exposure of Ogg1(-/-) mice to KBrO(3). Of particular
      note, the amount of 8-OH-G in kidney DNA from Ogg1(-/-) mice treated with KBrO(3)
      was approximately 70 times that of KBrO(3)-treated Ogg1(+/+) mice. The
      accumulated 8-OH-G did not decrease 4 weeks after discontinuing treatment with
      KBrO(3). KBrO(3) treatment for 12 weeks gave rise to increased mutation
      frequencies at the transgenic gpt gene in Ogg1(+/+) mice kidney. Absence of the
      Ogg1 gene further enhanced the mutation frequency. Sequence data obtained from
      gpt mutants showed that the accumulated 8-OH-G caused mainly GC-->TA transversion
      and deletion. Other mutations including GC-->AT transition also showed a tendency
      to increase. These results indicate that 8-OH-G, produced by chronic exposure to
      exogenous oxidative stress agents, is not repaired to any significant extent
      within the overall genome of Ogg1(-/-) mice kidney.

PMID- 12507923
TI  - Mutant p53-dependent growth suppression distinguishes PRIMA-1 from known
      anticancer drugs: a statistical analysis of information in the National Cancer
      Institute database.
AB  - We recently identified PRIMA-1 as a low molecular weight compound that restores
      tumor suppressor function to mutant p53 proteins and has anti-tumor activity in
      vivo (1). Here we report the statistical analysis of the effect of PRIMA-1 on a
      panel of human tumor cell lines using information available in a database at the
      Developmental Therapeutics Program of the National Cancer Institute (NCI). We
      extracted growth inhibition profiles for PRIMA-1 and 44 known anticancer agents,
      p53 status of cell lines, population doubling time, and level of p53 protein
      expression from the NCI database. The data were analyzed by linear regression,
      Wilcoxon matched pairs test, and cluster analysis. In a subset of human cell
      lines derived from colon, ovarian, renal, and non-small cell lung cancer and
      melanoma, the level of mutant p53 expression correlated with cell population
      doubling time, r = -0.53, P = 0.018. The GI(50) values for PRIMA-1 correlated
      with levels of mutant p53, r = -0.75, P = 0.0002. PRIMA-1 showed a statistically
      significant preference at P = 0.04 for growth inhibition of tumor cell lines
      expressing mutant p53 as compared with lines expressing wild-type p53. In
      contrast, none of several known anticancer drugs showed such preference. PRIMA-1
      inhibited the growth of cell lines derived from various human tumor types in a
      mutant p53-dependent manner. This distinguishes PRIMA-1 from known anticancer
      drugs and supports the idea that PRIMA-1 can serve as a lead for the development
      of novel therapeutic compounds.

PMID- 12507924
TI  - Increased metabolizing activities of the tricarboxylic acid cycle and decreased
      drug metabolism in hepatocellular carcinoma.
AB  - The aim of this study was to determine the metabolizing activities in the liver
      of patients with hepatocellular carcinoma (HCC). Thin-layer chromatography
      autoradioluminography was used to measure metabolizing activities. Succinate
      producing activity (SPA) was used as an indicator of metabolizing activity of the
      tricarboxylic acid (TCA) cycle in mitochondria, and diazepam-N-demethylating
      activity (DZ-DA), diazepam-3-hydroxylating activity (DZ-HA) and tolbutamide
      methyl-hydroxylating activity (TB-HA) as indicators of drug metabolizing
      activities by P-450. SPA and drug-metabolizing activity of HepG2 cells were
      examined to compare with those of human liver specimens. Liver biopsy specimens
      of 30 patients and surgical specimens of eight patients with HCC were studied.
      SPA of HepG2 cells was as high as that of human tumor tissue, and DZ-DA, DZ-HA
      and TB-HA were undetectable in HepG2 cells. SPA and DZ-HA of non-tumor tissue in
      biopsy samples were significantly higher than those in resected liver specimens
      (P < 0.05). In biopsy specimens, SPA was significantly higher in tumor tissue
      than in non-tumor tissue (P < 0.05), and DZ-DA, DZ-HA and TB-HA were
      significantly lower in tumor tissue (P < 0.01). SPA was significantly higher in
      large tumors (>/=30 mm) than in small tumors <30 mm (P < 0.05), and TB-HA was
      significantly lower in large tumors than in small tumors (P < 0.01). DZ-DA and TB
      HA significantly decreased with the progression of the tumor differentiation (P <
      0.05). In conclusion, HCC has increased metabolizing activities of the TCA cycle
      and decreased drug-metabolizing activities.

PMID- 12507925
TI  - The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is
      not dependent on DNA methylation.
AB  - Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is
      composed of two main components: hTERT and hTERC. hTERT seems to be the rate
      limiting factor for telomerase activity, although hTERC expression was also shown
      to correlate to a certain extent with telomerase reactivation. To determine
      whether the absence of hTERC expression could be the consequence of DNA
      methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative
      normal tissues, nine telomerase-positive and 22 telomerase-negative tumor
      tissues, eight telomerase-positive and two telomerase-negative cell lines) using
      a quantitative dot blot on RT-PCR products. Most of the normal tissues did not
      express hTERC whereas, in telomerase-positive cell lines and in telomerase
      positive tumor tissues, a strong up-regulation was observed, suggesting that
      hTERC transcription is up-regulated during tumorigenesis. The two telomerase
      negative cell lines did not express hTERC. In a series of 22 telomerase-negative
      soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly,
      whereas a wide range of expression was observed in the other half. As methylation
      might be involved in hTERC silencing, we examined the methylation pattern in all
      samples by direct sequencing and methylation-specific single stand conformation
      analysis after bisulfite modification. hTERC methylation was never observed,
      neither in normal nor in tumor tissues. Furthermore, there was no correlation
      between hTERC expression and proliferation, telomere length or hTERT expression
      in telomerase-negative STS. In contrast, three of eight telomerase-positive cell
      lines and the two telomerase negative cell lines were found to be
      hypermethylated, suggesting that the methylation observed may occur during cell
      line establishment. In conclusion, this study shows that hTERC expression is
      indeed regulated during carcinogenesis, but this regulation is unlikely to depend
      on hTERC methylation, cell proliferation rate, telomere length or hTERT
      expression.

PMID- 12507926
TI  - Inositol hexakisphosphate blocks tumor cell growth by activating apoptotic
      machinery as well as by inhibiting the Akt/NFkappaB-mediated cell survival
      pathway.
AB  - It has been reported that inositol hexakisphosphate (InsP(6), phytic acid), a
      natural product, has an anticancer role. However, there is inadequate information
      regarding the mechanism by which InsP(6) exerts anticancer actions, and the
      effect requires relatively high concentration of the agent, both of which hinders
      the usage of InsP(6) as an anticancer drug. In the present study, we investigated
      the mechanism by which InsP(6) acts as an anticancer agent, and tried to reduce
      the concentration of effective InsP(6). Treatment of HeLa cells with InsP(6) at 1
      mM induced apoptosis, as assessed by counting the cell number, and by Hoechst and
      TUNEL staining. This is probably mediated by intracellular InsP(6) itself and/or
      the dephosphorylated forms of metabolized InsP(6), because incubation of HeLa
      cells with [(3)H]InsP(6) produces dephosphorylated forms such as InsP(4) and
      InsP(5). Induction of apoptosis by InsP(6) was examined in two ways: inhibition
      of cell survival signaling and direct induction of apoptosis. Treatment of HeLa
      cells with tumor necrosis factor (TNF) or insulin stimulated the Akt-nuclear
      factor kappaB (NFkappaB) pathway, a cell survival signal, which involves the
      phosphorylation of Akt and IkappaB, nuclear translocation of NFkappaB and
      NFkappaB-luciferase transcription activity. InsP(6) blocked all these cellular
      events, but phosphatidylinositol 3-kinase activity was not affected. As well as
      inhibiting the Akt-NFkappaB pathway, InsP(6) itself caused mitochondrial
      permeabilization, followed by cytochrome c release, which later caused activation
      of the apoptotic machinery, caspase 9, caspase 3 and poly (ADP-ribose)
      polymerase. When InsP(6) was applied together with histone, the effective
      concentration to induce apoptosis was approximately 10-fold lower. These results
      revealed that extracellularly applied InsP(6) directly activates the apoptotic
      machinery as well as inhibits the cell survival signaling, probably by the
      intracellular delivery followed by a dephosphorylation.

PMID- 12507927
TI  - Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts:
      validation by comparison with other methods, and use in human biomonitoring.
AB  - A chemiluminescence immunoassay (CIA) utilizing antiserum elicited against DNA
      modified with (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10
      tetrahydrobenzo[a]- pyrene (BPDE) has been developed and validated to study the
      formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human tissues.
      Advantages include a low limit of detection for 10b-(deoxyguanosin-N(2)-yl)
      7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG,
      approximately 1.5 adducts/10(9) nucleotides using 20 micro g DNA) and a high
      signal-to-noise ratio (> or =100). The CIA BPDE-DNA standard curve gave 50%
      inhibition at 0.60 +/- 0.08 fmol BPdG (mean +/- SE, n = 30), which was a 10-fold
      increase in sensitivity compared with the dissociation-enhanced lanthanide
      fluoroimmunoassay (DELFIA). Calf thymus DNA modified with [1,3-(3)H]BPDE was
      assayed by radiolabeling, (32)P-postlabeling, DELFIA and CIA, and all assays gave
      similar values. Liver DNAs from mice exposed to 0.5 and 1.0 mg [7,8
      (3)H]benzo[a]pyrene (BP) were assayed by the same four assays and a dose-response
      was obtained with all assays. The BPDE-DNA CIA was further validated in MCL-5
      cells exposed to 4 micro M BP for 24 h, where nuclear and mitochondrial DNA
      adduct levels were associated with an increase in DNA tail length measured by the
      Comet assay. Human peripheral blood cell (buffy coat) DNA samples (n = 43)
      obtained from 25 individuals who were either colorectal adenocarcinoma patients
      or controls were assayed by BPDE-DNA CIA. Three samples (7%) were non-detectable,
      and the remaining 40 samples had values between 0.71 and 2.21 PAH-DNA
      adducts/10(8) nucleotides. The intra-assay coefficient of variation (CV), for
      four wells on the same microtiter plate, was 1.85%. Sufficient DNA for two
      assays, on separate plates, was available for 38 of the 43 samples, and the PAH
      DNA adduct values obtained were highly correlated (r(2) = 0.95). Coded duplicate
      DNA samples from 15 individuals were assayed four times gave an inter-assay CV of
      13.8%.

PMID- 12507928
TI  - The rate of increase in the numbers of primary sporadic basal cell carcinomas
      during follow up is associated with age at first presentation.
AB  - Basal cell carcinoma (BCC) patients demonstrate marked variation in tumour
      numbers and site. Previous studies also show an association between age at first
      BCC presentation and development of BCC on the trunk. In this study we have
      investigated the association between age at first presentation and the rate of
      development of truncal and non-truncal tumours in 747 patients with BCC. We used
      negative binomial regression analysis to show that increasing age at first
      presentation was associated with an increased rate of BCC development (rate ratio
      1.01/year, 95% CI 1.01-1.02, P < 0.001). In particular, development of tumours
      was greater in cases aged 60.0-69.9, 70.0-79.9 and 80.0-89.9 years than in those
      40.0-49.9 years (P = 0.05, 0.01 and 0.039, respectively). While few cases aged
      over 70 years of age first present with a truncal BCC, the numbers of BCC/year
      were greater than in those with a head/neck BCC. The data suggest different
      genetic factors mediate the appearance of BCC in patients of different ages
      particularly those aged above and below 60 years.

PMID- 12507929
TI  - Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal
      cancer risk in the Singapore Chinese Health Study.
AB  - Dietary intake of cruciferous vegetables (Brassica spp.) has been inversely
      related to colorectal cancer risk, and this has been attributed to their high
      content of glucosinolate degradation products such as isothiocyanates (ITCs).
      These compounds act as anticarcinogens by inducing phase II conjugating enzymes,
      in particular glutathione S-transferases (GSTs). These enzymes also metabolize
      ITCs, such that the protective effect of cruciferous vegetables may predicate on
      GST genotype. The Singapore Chinese Health Study is a prospective investigation
      among 63 257 middle-aged men and women, who were enrolled between April 1993 and
      December 1998. In this nested case-control analysis, we compared 213 incident
      cases of colorectal cancer with 1194 controls. Information on dietary ITC intake
      from cruciferous vegetables, collected at recruitment via a semi-quantitative
      food frequency questionnaire, was combined with GSTM1, T1 and P1 genotype from
      peripheral blood lymphocytes or buccal mucosa. When categorized into high
      (greater than median) and low (less than/equal to median) intake, dietary ITC was
      slightly lower in cases than controls but the difference was not significant
      [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.59-1.12]. There were no
      overall associations between GSTM1, T1 or P1 genotypes and colorectal cancer
      risk. However, among individuals with both GSTM1 and T1 null genotypes, we
      observed a 57% reduction in risk among high versus low consumers of ITC (OR 0.43,
      95% CI 0.20-0.96), in particular for colon cancer (OR 0.31, 0.12-0.84). Our
      results are compatible with the hypothesis that ITCs from cruciferous vegetables
      modify risk of colorectal cancer in individuals with low GST activity. Further,
      this gene-diet interaction may be important in studies evaluating the effect of
      risk-enhancing compounds in the colorectum.

PMID- 12507931
TI  - Comparison of multiple DNA adduct types in tumor adjacent human lung tissue:
      effect of cigarette smoking.
AB  - Cigarette smokers inhale a broad range of carcinogens derived from tobacco and
      its pyrolysis products, including free radicals, which induce oxidative stress
      and subsequent lipid peroxidation (LPO). Miscoding carcinogen-DNA adducts are
      formed by cigarette smoke constituents and are thought to initiate lung
      carcinogenesis. The presence of various types of DNA damage was therefore
      analyzed in tumor adjacent uninvolved lung tissues of 13 smoking and 11 non
      smoking operated lung cancer patients. O(4)-ethylthymidine (O(4)etT), 1,N(6)
      ethenodeoxyadenosine ( epsilon dA) and 3,N(4)-ethenodeoxycytidine ( epsilon dC)
      were determined by immuno-enriched (32)P-postlabeling. Polycyclic aromatic
      hydrocarbon (PAH)-DNA adducts were measured as diagonal radioactive zones after
      nuclease P1 enriched (32)P-postlabeling. Mean O(4)etT and PAH-DNA adduct levels
      were higher in lung DNA of smokers than of non-smokers (O(4)etT/10(8) thymidine:
      3.8 versus 1.6, P < 0.01; PAH-DNA adducts/10(8) nucleotides: 11.2 versus 2.2, P <
      0.01). Pulmonary etheno-DNA adduct levels did not differ between smokers and non
      smokers, but large inter-individual variations were observed (80- and 250-fold
      differences for epsilon dA and epsilon dC, respectively). As all smokers (except
      one) refrained from smoking at least for 1 week before surgery, our results
      demonstrate the persistence of O(4)etT and PAH-DNA adducts in human lung. A
      positive correlation obtained between O(4)etT and PAH-DNA adducts (R = 0.65, P <
      0.01) suggests that both adducts are formed from cigarette smoke as the main
      exposure source. We conclude that in addition to the DNA adducts derived from PAH
      and tobacco-specific nitrosamines, miscoding O(4)etT lesions are formed by
      cigarette smoke that contribute to the increased genomic instability and
      increased lung cancer risk in smokers.

PMID- 12507930
TI  - Development and molecular characterization of HCT-116 cell lines resistant to the
      tumor promoter and multiple stress-inducer, deoxycholate.
AB  - Evidence from live cell bioassays shows that the flat mucosa from patients with
      colon cancer exhibits resistance to bile salt-induced apoptosis. Three
      independent cell lines derived from the colonic epithelial cell line HCT-116 were
      selected for resistance to bile salt-induced apoptosis. These cell lines were
      developed as tissue culture models of apoptosis resistance. Selection was carried
      out for resistance to apoptosis induced by sodium deoxycholate (NaDOC), the bile
      salt found in highest concentrations in human fecal water. Cultures of HCT-116
      cells were serially passaged in the presence of increasing concentrations of
      NaDOC. The resulting apoptosis resistant cells were able to grow at
      concentrations of NaDOC (0.5 mM) that cause apoptosis in a few hours in
      unselected HCT-116 cells. These cells were then analyzed for changes in gene
      expression. Observations from cDNA microarray, 2-D gel electrophoresis/MALDI-mass
      spectroscopy, and confocal microscopy of immunofluorescently stained preparations
      indicated underexpression or overexpression of numerous genes at either the
      protein or mRNA level. Genes that may play a role in apoptosis and early stage
      carcinogenesis have been identified as upregulated in these cell lines, including
      Grp78, Bcl-2, NF-kappaB(p50), NF-kappaB(p65), thioredoxin peroxidase
      (peroxiredoxin) 2, peroxiredoxin 4, maspin, guanylate cyclase activating protein
      1, PKCzeta, EGFR, Ras family members, PKA, PI(4,5)K, TRAF2 and BIRC1 (IAP
      protein). Under-expressed mRNAs included BNIP3, caspase-6, caspase-3 and serine
      protease 11. NF-kappaB was constitutively activated in all three resistant cell
      lines, and was responsible, in part, for the observed apoptosis resistance,
      determined using antisense oligonucleotide strategies. Molecular and cellular
      analyses of these resistant cell lines has suggested potential mechanisms by
      which apoptosis resistance may develop in the colonic epithelium in response to
      high concentrations of hydrophobic bile acids that are associated with a Western
      style diet. These analyses provide the rationale for the development of
      hypothesis-driven intermediate biomarkers to assess colon cancer risk on an
      individual basis.

PMID- 12507932
TI  - Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation
      but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells.
AB  - Boswellic acids are the effective components of gum resin of Boswellia serrata,
      which has anti-inflammatory properties. Recent studies on brain tumors and
      leukemic cells indicate that boswellic acids may have antiproliferative and
      apoptotic effects with the mechanisms being not studied in detail. We studied
      their antiproliferative and apoptotic effects on colon cancer cells and the
      pathway leading to apoptosis. HT-29 cells were treated with beta-boswellic acid
      (BA), keto-beta-boswellic acid (K-BA) and acetyl-keto-beta-boswellic acid (AK
      BA), respectively. Apoptosis was determined by flow cytometry, by cytoplasmic DNA
      histone complex and the activity of caspase-3. The cleavage of poly-(ADP-ribose)
      polymerase (PARP) and expression of Fas were examined by western blot. Specific
      caspase inhibitors, polyclonal Fas antibody, and antagonistic Fas antibody ZB4
      were employed to elucidate apoptotic pathways. DNA synthesis and cell viability
      were examined. Both K-BA and AK-BA increased cytoplasmic DNA-histone complex dose
      dependently and increased pre-G(1) peak in flow cytometer analysis, with the
      effects of AK-BA being stronger than K-BA. BA only increased the formation of DNA
      histone complex at a high concentration. K-BA and AK-BA increased caspase-8,
      caspase-9 and caspase-3 activities accompanied by cleavage of PARP. The effects
      of AK-BA on formation of cytoplasmic DNA histone and on caspase-3 activation were
      3.7- and 3.4-fold, respectively, more effective than those induced by
      camptothecin. The apoptosis induced by AK-BA was inhibited completely by caspase
      3 or caspase-8 inhibitor and partially by caspase-9 inhibitor. ZB4 blocked
      exogenous Fas ligand-induced apoptosis, but had no effect on AK-BA-induced
      apoptosis. AK-BA had no significant effect on expression of Fas. Apart from
      apoptotic effect, these acids also inhibited [(3)H]thymidine incorporation and
      cell viability to different extent. In conclusion, boswellic acids, particularly
      AK-BA and K-BA have antiproliferative and apoptotic effects in human HT-29 cells.
      The apoptotic effect is mediated via a pathway dependent on caspase-8 activation
      but independent of Fas/FasL interaction.

PMID- 12507933
TI  - Aberrant arachidonic acid metabolism in esophageal adenocarcinogenesis, and the
      effects of sulindac, nordihydroguaiaretic acid, and alpha-difluoromethylornithine
      on tumorigenesis in a rat surgical model.
AB  - Human esophageal adenocarcinoma (EAC) develops in a sequence from
      gastroesophageal reflux disease (GERD), columnar-lined esophagus (CLE),
      dysplasia, and eventually to EAC. We established a rat surgical EAC model with
      esophagogastroduodenal anastomosis (EGDA) to mimic the staged process of
      esophageal adenocarcinogenesis. Profiling of the AA metabolites with mass
      spectrometry showed that prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 15
      hydroeicosatetraenoic acid (HETE), 12-HETE, 8-HETE and 5-HETE all increased at
      the esophagoduodenal junction after EGDA as compared with the proximal esophagus,
      with PGE2 as the major metabolite. Consistent with this profile, cyclooxygenase 2
      (Cox2) was overexpressed in the basal cell layer of esophageal squamous
      epithelium, CLE cells and EAC tumor cells of the EGDA rats, as compared with the
      normal esophageal epithelium. Sulindac (a Cox inhibitor), nordihydroguaiaretic
      acid (NDGA, a lipoxygenase inhibitor) and alpha-difluoromethylornithine (DFMO, an
      ornithine decarboxylase inhibitor) were tested for their possible inhibitory
      actions against the formation of EAC in the rat EGDA model. In a short-term study
      (for 4 weeks after surgery), dietary administration of both sulindac (300 and 600
      p.p.m.) and NDGA (100 p.p.m.) effectively reduced the EGDA-induced inflammation.
      In a long-term chemoprevention study (for 40 weeks after surgery), 300 p.p.m.
      sulindac, alone or in combination with 100 p.p.m. NDGA or 0.5% DFMO, decreased
      the tumor incidence from 57.7 to 26.9%, or 16.7 or 20%, respectively (P < 0.05).
      NDGA alone (100 and 200 p.p.m.) slightly decreased the tumor incidence to 52.4
      and 37%, respectively, although the difference was not statistically significant.
      DFMO alone did not show significant effects on tumor incidence. Inhibition of
      tumor formation by sulindac was correlated with lowered levels of PGE2. In
      conclusion, sulindac exerted its chemopreventive effect against the formation of
      EAC in the rat EGDA model possibly through its inhibition of Cox.

PMID- 12507934
TI  - Vitamin D(3) receptor ablation sensitizes skin to chemically induced
      tumorigenesis.
AB  - 1,25-Dihydroxyvitamin D(3) (1,25D(3)) is the biologically active form of vitamin
      D(3) that interacts with the nuclear vitamin D(3) receptor (VDR) to modulate gene
      expression in a tissue-specific fashion. 1,25D(3) is a potent regulator of cell
      proliferation, differentiation and apoptosis in a variety of cell types,
      including keratinocytes. In these studies, we assessed the sensitivity of mice
      homozygous for a null allele of the VDR (VDR(-/-) mice) and their wild-type
      counterparts (VDR(+/+) mice) to oral administration of the carcinogen 7,12
      dimethylbenzanthracene (DMBA). Although the protocol was optimized for the
      induction of mammary tumors, 85% of VDR(-/-) mice developed persistent skin
      tumors within 60 days of carcinogen exposure. In VDR(-/-) mice exposed to DMBA,
      papillomas arose on all areas of the body, with an average tumor burden of 5.3
      papillomas/mouse. No papillomas or any other skin lesions were observed in age-
      and sex-matched VDR(+/+) mice dosed with DMBA and followed for 6 months. The
      majority (80%) of skin tumors that developed in VDR(-/-) mice were classified
      histologically as sebaceous, squamous or follicular papillomas. Other types of
      lesions, including basal cell carcinoma, hemangioma and melanotic foci, were
      occasionally observed in VDR(-/-) mice (but not in VDR(+/+) mice) exposed to
      DMBA. Quantification of epidermal thickness and BrdU incorporation indicated that
      skin from VDR(-/-) mice exhibited hyperproliferation beginning at 7 weeks of age,
      which was exacerbated by DMBA treatment. Untreated aging VDR(-/-) mice did not
      exhibit tumor formation, but did develop a progressive skin phenotype
      characterized by thickened wrinkled skin, dermoid cysts and long curly nails.
      Together with previous reports that 1,25D(3) inhibits papilloma formation induced
      by topical DMBA-TPA regimens, our observation of enhanced sensitivity of VDR(-/-)
      mice to chemically induced skin carcinogenesis offers compelling evidence that
      disruption of VDR signaling predisposes to neoplasia.

PMID- 12507935
TI  - Association of p16(INK4a) and pRb inactivation with immortalization of human
      cells.
AB  - To examine the association of cell cycle regulatory gene inactivation with human
      cell immortalization, we determined the expression status of INK4a, Rb, and WAF1/
      CIP1, in eleven in vitro immortalized human cell lines, including fibroblasts and
      keratinocytes. Two human papillomavirus type 16 E6 expressing cell lines with
      telomerase activity, including a fibroblast cell line and a keratinocyte cell
      line, expressed no detectable p16(INK4a). These cell lines had a
      hyperphosphorylated pRb and reduced expression of p21(WAF1/CIP1). All of seven
      fibroblast cell lines immortalized either spontaneously or by (60)Co, X-rays, 4
      nitroquinoline 1-oxide or aflatoxin B(1), maintaining their telomeres by the ALT
      (alternative lengthening of telomeres) pathway, displayed loss of expression of
      p16(INK4a) and hyperphosphorylation of pRb. Levels of p21(WAF1/CIP1) expression
      varied among the cell lines. Two fibroblast cell lines that became immortalized
      following infection with a retrovirus vector encoding human telomerase catalytic
      subunit (hTERT) cDNA were also accompanied by inactivation of p16(INK4a) and pRb
      pathways. Acquisition of telomerase activity alone was not sufficient for
      immortalization of these cell lines. Taken together, all the cell lines including
      fibroblasts and keratinocytes, with either telomerase activity or the ALT pathway
      for telomere maintenance showed loss of expression of p16(INK4a) and
      hyperphosphorylation of pRb. These demonstrate the association of inactivation of
      both p16(INK4a) and pRb with immortalization of human cells including fibroblasts
      and epithelial cells and telomerase-positive cells and ALT-positive cells.

PMID- 12507936
TI  - Matrix metalloproteinase(s) mediate(s) NO-induced dissociation of beta-catenin
      from membrane bound E-cadherin and formation of nuclear beta-catenin/LEF-1
      complex.
AB  - Modulation of the adenomatous polyposis coli (APC)-beta-catenin pathway by
      inflammatory mediators and extracellular matrix may be important in colon
      carcinogenesis. We have recently shown that nitric oxide (NO) induces the
      accumulation of cytosolic beta-catenin and subsequent formation of the nuclear
      beta-catenin/lymphocyte enhancing factor (LEF)-1 complex in conditionally
      immortalized young mouse colonic epithelial (YAMC) cells. In the present study,
      we explored the mechanism(s) through which NO exerts its effect on cytosolic beta
      catenin accumulation and nuclear beta-catenin/LEF-1 complex formation. We found
      that NO-induced degradation of the membrane bound E-cadherin at tight junctions.
      Using an anti-E-cadherin antibody specific for its extracellular domain, we
      detected a 50kDa degradation fragment of E-cadherin (120 kDa) from the culture
      medium conditioned by YAMC cells exposed to the NO-releasing drug, NOR-1, for 4
      and 24 h. As beta-catenin is normally bound to transmembrane E-cadherin and thus
      anchored to the cytoskeleton structure, the degradation of E-cadherin induced by
      NO may cause dissociation of beta-catenin from membrane bound E-cadherin. This
      was demonstrated by the detection of beta-catenin accumulation in the soluble
      cytosolic fractions in YAMC after exposure to NO-releasing drugs. Furthermore,
      the degradation of E-cadherin and the release of beta-catenin to cytosol were
      accompanied by the formation of nuclear beta-catenin/LEF-1 complex, demonstrating
      the dissociation of beta-catenin from E-cadherin may be responsible for the
      activation of beta-catenin/LEF-1 transcription complex. Co-treatment with NO
      donors and broad-spectrum matrix metalloproteinase (MMP) inhibitors TIMP-1 (100
      ng/ml), GM6001 (10 micro M) and GM1489 (10 micro M) abolished the degradation of
      E-cadherin induced by NO as demonstrated by western blot analysis. These MMP
      inhibitors also blocked the cytosolic accumulation of beta-catenin and nuclear
      formation of beta-catenin/LEF-1 complex. The sum effect of MMP inhibitors
      demonstrated that NO-induced activation of MMP may cause the degradation of E
      cadherin and the subsequent dissociation of beta-catenin, thereby contributing to
      the cytosolic accumulation of beta-catenin and nuclear formation of beta
      catenin/LEF-1 complex.

PMID- 12507937
TI  - H-ras oncogene mutations during development of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary gland cancer.
AB  - Laser capture microdissection, polymerase chain reaction-restriction fragment
      length polymorphism analysis, and DNA sequencing was used to detect H-ras codon
      12 and 13 mutations during the stages of mammary gland cancer development in rats
      exposed to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen
      found in cooked meat. Ten oral doses of PhIP (75 mg/kg, p.o., once per day) were
      administered to adolescent female Sprague-Dawley rats and mammary glands examined
      histologically for intraductal proliferations (IDPs), carcinoma in situ and
      carcinomas 7-14 weeks later. Mammary gland epithelial cells from normal tissue
      and distinct lesions were collected from glass slides and analyzed for mutations.
      H-ras codon 12/13 mutations were detected in 73%, 75%, 100%, and 100% of normal
      mammary glands, IDPs, carcinoma in situ, and carcinoma, respectively, after PhIP
      treatment. The spectrum of activating mutations included G(35) to A or C base
      substitution mutations in codon 12, and G(37) to T or A base substitution
      mutations in codon 13. The spectrum of H-ras mutations was similar among normal
      mammary gland from PhIP treated rats, preneoplastic lesions, and carcinomas.
      Furthermore, the spectrum of mutations was consistent with the involvement of
      PhIP-guanine adduct formation. The results support the notion that mutations in H
      ras codons 12 and 13 are largely PhIP-DNA adduct-induced and involved in the
      initiation and development of mammary gland cancer in rats exposed to PhIP.

PMID- 12507938
TI  - Comparative analysis of baseline 8-oxo-7,8-dihydroguanine in mammalian cell DNA,
      by different methods in different laboratories: an approach to consensus.
AB  - The European Standards Committee on Oxidative DNA Damage (ESCODD) was set up to
      resolve the problems associated with the measurement of background levels of
      oxidative DNA damage (in particular 8-oxo-7,8-dihydroguanine, or 8-oxoGua) in
      human cells. A tendency for DNA oxidation to occur during sample preparation
      prior to chromatography has been recognized as the source of a very substantial
      artefact. To assess the success of attempts to eliminate the artefact, ESCODD has
      distributed to its members standard samples of pig liver and HeLa cells for
      analysis. Estimates of 8-oxoGua in pig liver, using chromatographic techniques,
      ranged from 2.23 to 441 per 10(6) guanines, with a median of 10.47 per 10(6)
      guanines. Chromatographic analysis of HeLa cell DNA gave a range of 1.84 to 214
      per 10(6) guanines with a median of 5.23 per 10(6) guanines. HeLa cell DNA was
      also analysed by an enzymic approach, in which whole cell DNA was treated with
      formamidopyrimidine DNA glycosylase, which nicks DNA at sites of 8-oxoGua, and
      the breaks measured with the comet assay, alkaline unwinding or alkaline elution.
      Values with these methods ranged from 0.06 to 4.988-oxoGua per 10(6) guanines,
      with a median of 0.79 per 10(6) guanines. Although there are clearly still
      serious discrepancies between methods and laboratories, the lowest estimates by
      chromatography (arguably those in which the artefact was best controlled) are
      only 2.5 times higher than the median value obtained with the enzymic approach.

PMID- 12507939
TI  - Proper controls for SNP studies?

PMID- 12507942
TI  - The changing number of cells in the human fetal forebrain and its subdivisions: a
      stereological analysis.
AB  - The total number of cells--including both neurons and glial cells - was estimated
      in the neocortical part of the human fetal telencephalon in 22 normal brains
      within four major developmental zones: the cortical plate/marginal zone, the
      subplate, the intermediate zone and the ventricular/subventricular zone. The
      fetal ages ranged from 13 to 41 weeks of gestation. The cellular growth in the
      human fetal forebrain appears to be two-phased: one rapid, exponential phase from
      13 to 20 weeks of gestation and a second and slower phase, which increases
      linearly, from approximately 22 weeks of gestation to term. From 13 to 20 weeks
      of gestation the total number of cells increases by a factor of 4.3 from 3 x
      10(9) cells to 13 x 10(9) cells at 20 weeks of gestation. From mid-gestation to
      term, the total cell number increases by a factor of 2.9 to 38 x 10(9) cells in
      the newborn infant. Studying cellular growth in the normal human fetal brain is
      important since it may serve as a useful parameter for the assessment of cortical
      growth in non-invasive and histological studies, and thus improve the analysis of
      fetal brain disturbances.

PMID- 12507943
TI  - Regulation of depotentiation and long-term potentiation in the dentate gyrus of
      freely moving rats by dopamine D2-like receptors.
AB  - Dopamine receptors are significantly involved in hippocampus-based cognitive
      processes. Whereas the involvement of D1-like receptors in hippocampal plasticity
      has been described, the role of D2-like receptors remains to be clarified.
      Therefore, we investigated the contribution of D2-like receptors to synaptic
      transmission, long-term potentiation (LTP) and depotentiation in the dentate
      gyrus of freely moving rats. Male Wistar rats underwent chronic implantation of a
      recording electrode in the granule cell layer, a stimulating electrode in the
      medial perforant path and a cannula in the ipsilateral cerebral ventricle (to
      enable drug administration). The D2-like receptor agonists quinpirole and
      noraporphine dose-dependently inhibited basal synaptic transmission. Agonist
      priming of D2-like receptors with a drug concentration which had no effect on
      synaptic transmission inhibited depotentiation but did not affect LTP. The
      agonist effects on depotentiation were prevented by the D2-like antagonist
      remoxipride. Remoxipride itself did not influence basal synaptic transmission or
      depotentiation. Interestingly, 'weak' LTP (<4 h) but not 'strong' LTP (>24 h) was
      inhibited by prior application of remoxipride. These results suggest a specific
      role for dopamine D2-like receptors in the regulation of both depotentiation and
      LTP in vivo and offer an important and novel insight as to the involvement of
      these receptors in processes related to learning and memory.

PMID- 12507944
TI  - Presynaptic frequency filtering in the gamma frequency band; dual intracellular
      recordings in slices of adult rat and cat neocortex.
AB  - Using dual intracellular recordings in slices of adult rat and cat neocortex, the
      frequency-filtering characteristics of 'depressing' synapses made by pyramidal
      axons at interspike intervals between 5 and 50 ms were studied. At 'depressing'
      connections from excitatory cells to some inhibitory interneurons (n = 6),
      recovery from short interspike interval depression was near exponential.
      Extrapolation of exponentials fitted to this recovery demonstrated a residual 10
      20% depression at intervals >50 ms. This slowly decaying component was larger for
      later excitatory postsynaptic potentials (EPSPs) in trains which were typically
      more strongly depressed. At >80% of connections between spiny excitatory cells
      and at pyramid to parvalbumin-immunopositive interneuron connections, however,
      recovery exhibited a more complex time course. A narrow 'notch' (half-width 5
      ms), peaking at intervals of 13-25 ms during which the EPSP was depressed
      further, interrupted recovery from short interval depression. This 'notch' was
      equally apparent for all EPSPs in brief trains and was mediated presynaptically.

PMID- 12507946
TI  - Brain imaging of language plasticity in adopted adults: can a second language
      replace the first?
AB  - Do the neural circuits that subserve language acquisition lose plasticity as they
      become tuned to the maternal language? We tested adult subjects born in Korea and
      adopted by French families in childhood; they have become fluent in their second
      language and report no conscious recollection of their native language. In
      behavioral tests assessing their memory for Korean, we found that they do not
      perform better than a control group of native French subjects who have never been
      exposed to Korean. We also used event-related functional magnetic resonance
      imaging to monitor cortical activations while the Korean adoptees and native
      French listened to sentences spoken in Korean, French and other, unknown, foreign
      languages. The adopted subjects did not show any specific activations to Korean
      stimuli relative to unknown languages. The areas activated more by French stimuli
      than by foreign stimuli were similar in the Korean adoptees and in the French
      native subjects, but with relatively larger extents of activation in the latter
      group. We discuss these data in light of the critical period hypothesis for
      language acquisition.

PMID- 12507945
TI  - Practice and difficulty evoke anatomically and pharmacologically dissociable
      brain activation dynamics.
AB  - Brain activation is adaptive to task difficulty and practice. We used functional
      MRI to map brain systems activated by an object-location learning task in 24
      healthy elderly volunteers each scanned following placebo and two of four active
      drugs studied. We distinguished a fronto-striatal system adaptive to difficulty
      from a posterior system adaptive to practice. Fronto-striatal response to
      increased cognitive load was significantly attenuated by scopolamine, sulpiride
      and methylphenidate; practice effects were not modulated by these drugs but were
      enhanced by diazepam. We also found enhancement by methylphenidate, and
      attenuation by sulpiride, of load response in premotor, cingulate and parietal
      regions comprising a spatial attention network. Difficulty and practice evoke
      anatomically and pharmacologically dissociable brain activation dynamics, which
      are probably mediated by different neurotransmitter systems in humans.

PMID- 12507947
TI  - Foot, hand, face and eye representation in the human striatum.
AB  - The present study aimed at determining the three-dimensional organization of
      striatal activation during foot, hand, face and eye movements. Seven right
      handed, healthy volunteers were studied at 1.5 T using blood oxygen level
      dependent (BOLD) contrast. The tasks consisted of self-paced flexion/extension of
      the right and left fingers and right toes, contraction of the lips and saccadic
      eye movements. For foot, hand and face movements, striatal activation was mainly
      found in the putamen with a somatotopical organization, the foot area being
      dorsal, the face area more ventral and medial, the hand area in between. Overlap
      between somatotopic territories was present, more prominent for hand-face than
      for foot-face or foot-hand areas. In the putamen, the activated areas of the ipsi
      and contralateral hand areas were not identical, suggesting a partial
      segregation of the ipsi- and contralateral striatal sensorimotor projections. For
      saccadic eye movements, bilateral activation was observed at the junction between
      the body and the head of the caudate nucleus and in the right putamen. These data
      present evidence for a somatotopic organization of the human striatum which
      corresponds with the topography of corticostriatal projections described in the
      non-human primates.

PMID- 12507948
TI  - The role of left inferior frontal and superior temporal cortex in sentence
      comprehension: localizing syntactic and semantic processes.
AB  - An event-related functional magnetic resonance imaging (fMRI) paradigm was used
      to specify those brain areas supporting the processing of sentence-level semantic
      and syntactic information. Hemodynamic responses were recorded while participants
      listened to correct, semantically incorrect and syntactically incorrect
      sentences. Both anomalous conditions recruited larger portions of the superior
      temporal region than correct sentences. Processing of semantic violations relied
      primarily on the mid-portion of the superior temporal region bilaterally and the
      insular cortex bilaterally, whereas processing of syntactic violations
      specifically involved the anterior portion of the left superior temporal gyrus,
      the left posterior frontal operculum adjacent to Broca's area and the putamen in
      the left basal ganglia. A comparison of the two anomalous conditions revealed
      higher levels of activation for the syntactic over the semantic condition in the
      left basal ganglia and for the semantic over the syntactic condition in the mid
      portion of the superior temporal gyrus, bilaterally. These data indicate that
      both semantic and syntactic processes are supported by a temporo-frontal network
      with distinct areas specialized for semantic and syntactic processes.

PMID- 12507949
TI  - Effects of surface cues on macaque inferior temporal cortical responses.
AB  - Humans are able to recognize objects when surface details, such as colour,
      texture and luminance gradients, are not available. By systematically eliminating
      colour, texture, shading, contrast and inner contours from given objects, we
      tested whether certain shape-selective inferior temporal cortex (IT) neurons of
      awake rhesus monkeys remain selective for these objects as the surface
      information is reduced. In psychophysical experiments, we established that the
      rhesus monkey can identify the shape of a coloured object largely independently
      of its surface characteristics and, to a lesser degree, of its inner contours.
      Shape selectivity of the neurons does not change when texture and shading are
      concealed. The responsiveness of the neurons is also affected by the removal of
      these surface attributes. The IT neurons were found to respond highly similarly
      to objects brighter or darker than their background. Selectivity for shape is
      preserved when the contrast is reversed. Deletion of the inner contours,
      outlining the main parts of the objects, did not affect the responses and
      selectivity of the IT neurons. These findings indicate that the IT can contribute
      to the invariant perception of objects having different surface details.

PMID- 12507950
TI  - The processing of kinetic contours in the brain.
AB  - This work investigates whether the brain assigns special cortical areas for the
      processing of kinetic contours. In human imaging experiments, we compared the
      brain activity produced in the so-called 'kinetic occipital' area ('KO') when
      humans perceive shapes generated from kinetic boundaries or from equiluminant
      colors. 'KO' was activated whenever subjects perceived shapes, no matter how they
      were derived; it is therefore not specialized for the processing of kinetic
      contours. The application of independent component analysis (ICA) to imaging data
      obtained when subjects viewed 22 min of an action movie showed that the time
      course of activity in 'KO' correlates better with activity in area V3 than with
      activity in two adjacent areas, V5 and LO. We thus consider 'KO' to be part of
      the V3 family of areas, and use the terminology of Smith et al. (J Neurosci
      18:3816-3830, 1998), to refer to it as area V3B. Recordings from orientation
      selective cells in the macaque V3 complex show that the great majority have the
      same orientational specificity when tested with oriented lines generated from
      kinetic stimuli or from luminance differences. We conclude that there is no
      present evidence for a visual area specialized for the processing of kinetic
      contours in the primate visual brain.

PMID- 12507951
TI  - Early differences in axonal outgrowth, cell migration and GABAergic
      differentiation properties between the dorsal and lateral cortex.
AB  - The regionalization of the cerebral cortex proceeds gradually from early
      embryonic stages under the control of transcription factors that are expressed in
      gradients. Two phases can be distinguished at the beginning of cortical
      development: the genesis of a precocious and transient structure, the preplate,
      which is followed by development of the cortical plate within the preplate.
      Cellular indices of early regionalization have not yet been described either in
      the preplate or in the early cortical plate. In the present study, we identify
      two regions, lateral and dorsal, in the mouse cortex embryo, which differ
      strongly in the functional properties of their early neurons. By using culture
      experiments and grafts on organotypic slices, we show that the earliest neurons
      in the dorsal cortex extend axons before and more rapidly than the earliest
      neurons in the lateral cortex. In contrast to the lateral cortex, the dorsal
      cortex differentiates neurons migrating along axons in vitro. These cells express
      markers of the GABAergic lineage. Early differences between the two regions
      suggest that the dorsal part of the cortex generates early neurons with
      particular intrinsic properties that may in turn specifically influence the later
      development of the cortical plate in this domain.

PMID- 12507952
TI  - Krieg Cortical Kudos 2002. The Cortical Discoverer Awards.

PMID- 12507953
TI  - Towards complete and accurate reporting of studies of diagnostic accuracy: the
      STARD initiative. Standards for Reporting of Diagnostic Accuracy.
AB  - BACKGROUND: To comprehend the results of diagnostic accuracy studies, readers
      must understand the design, conduct, analysis, and results of such studies. That
      goal can be achieved only through complete transparency from authors. OBJECTIVE:
      To improve the accuracy and completeness of reporting of studies of diagnostic
      accuracy to allow readers to assess the potential for bias in the study and to
      evaluate its generalisability. METHODS: The Standards for Reporting of Diagnostic
      Accuracy (STARD) steering committee searched the literature to identify
      publications on the appropriate conduct and reporting of diagnostic studies and
      extracted potential items into an extensive list. Researchers, editors, and
      members of professional organisations shortened this list during a two-day
      consensus meeting with the goal of developing a checklist and a generic flow
      diagram for studies of diagnostic accuracy. RESULTS: The search for published
      guidelines on diagnostic research yielded 33 previously published checklists,
      from which we extracted a list of 75 potential items. The consensus meeting
      shortened the list to 25 items, using evidence on bias whenever available. A
      prototypical flow diagram provides information about the method of patient
      recruitment, the order of test execution and the numbers of patients undergoing
      the test under evaluation, the reference standard or both. CONCLUSIONS:
      Evaluation of research depends on complete and accurate reporting. If medical
      journals adopt the checklist and the flow diagram, the quality of reporting of
      studies of diagnostic accuracy should improve to the advantage of clinicians,
      researchers, reviewers, journals, and the public.

PMID- 12507954
TI  - The STARD statement for reporting studies of diagnostic accuracy: explanation and
      elaboration.
AB  - The quality of reporting of studies of diagnostic accuracy is less than optimal.
      Complete and accurate reporting is necessary to enable readers to assess the
      potential for bias in the study and to evaluate the generalisability of the
      results. A group of scientists and editors has developed the STARD (Standards for
      Reporting of Diagnostic Accuracy) statement to improve the reporting the quality
      of reporting of studies of diagnostic accuracy. The statement consists of a
      checklist of 25 items and flow diagram that authors can use to ensure that all
      relevant information is present. This explanatory document aims to facilitate the
      use, understanding and dissemination of the checklist. The document contains a
      clarification of the meaning, rationale and optimal use of each item on the
      checklist, as well as a short summary of the available evidence on bias and
      applicability. The STARD statement, checklist, flowchart and this explanation and
      elaboration document should be useful resources to improve reporting of
      diagnostic accuracy studies. Complete and informative reporting can only lead to
      better decisions in healthcare.

PMID- 12507955
TI  - The STARD initiative and the reporting of studies of diagnostic accuracy.

PMID- 12507956
TI  - Effect of the systemic inflammatory response on biochemical markers of neonatal
      bacterial infection: a fresh look at old confounders.

PMID- 12507957
TI  - Use of high-throughput DNA microarrays to identify biomarkers for bladder cancer.
AB  - BACKGROUND: Numerous markers have been described to correlate to some extent with
      tumor stage and prognosis of patients with bladder cancer. The power of many of
      these biomarkers in detecting superficial disease or predicting the clinical
      outcome of individual tumors is limited, and alternative markers are still in
      demand. High-throughput microarrays represent novel means for cancer research and
      tumor marker discovery. APPROACH: The aim of this report was to discuss the
      application of DNA technologies to provide novel biomarkers for bladder cancer.
      CONTENT: Specific bladder tumor subtypes have distinct gene expression profiles.
      The use of high-throughput DNA microarrays allows identification of the most
      prevalent and relevant alterations within bladder tumors. Clusters of
      differentially expressed genes will become biomarkers to discriminate subgroups
      of patients with different histopathology or clinical outcome. Additionally, the
      identified individual molecular targets might be further validated and developed
      into novel serum or urinary biomarkers for the diagnosis and/or as prognostic
      factors to be applied in clinical practice. The diagnosis and prognosis of
      bladder cancer would be enhanced by the use of such markers, and the marker
      itself may constitute a therapeutic target when studied in appropriate patients
      and control groups. SUMMARY: Expression profiling with high-throughput DNA
      microarrays has the potential of providing critical clues for the management of
      bladder cancer patients. As the quality, standardization, and ease of use of the
      technology increase and the costs decrease, DNA microarrays will move from being
      a technology restricted to research to clinical laboratories in the near future.

PMID- 12507958
TI  - Angiogenesis assays: a critical overview.
AB  - BACKGROUND: Angiogenesis, the formation of new blood vessels, is an integral part
      of both normal developmental processes and numerous pathologies, ranging from
      tumor growth and metastasis to inflammation and ocular disease. Angiogenesis
      assays are used to test efficacy of both pro- and antiangiogenic agents. METHODS:
      Most studies of angiogenesis inducers and inhibitors rely on various models, both
      in vitro and in vivo, as indicators of efficacy. In this report we describe the
      principal methods now in use: the in vivo Matrigel plug and corneal
      neovascularization assays, the in vivo/in vitro chick chorioallantoic membrane
      (CAM) assay, and the in vitro cellular (proliferation, migration, tube formation)
      and organotypic (aortic ring) assays. We include description of two new methods,
      the chick aortic arch and the Matrigel sponge assays. CONCLUSIONS: In vitro tests
      are valuable, can be carried out expeditiously, and lend themselves to
      quantification, but must be interpreted with extreme caution. In vitro tests are
      best viewed as providing initial information, subject to confirmation by in vivo
      assays. Multiple tests should be used to obtain maximum benefit from in vitro
      tests. In vivo tests are more difficult and time-consuming to perform, thereby
      limiting the number of tests that can run at any one time. Quantification is
      generally more difficult as well. However, in vivo assays are essential because
      of the complex nature of vascular responses to test reagents, responses that no
      in vitro model can fully achieve.

PMID- 12507959
TI  - Windows to the ward: graphically oriented report forms. Presentation of complex,
      interrelated laboratory data for electrophoresis/immunofixation, cerebrospinal
      fluid, and urinary protein profiles.
AB  - BACKGROUND: Automated laboratory analyzers that mass produce data have been
      linked to information systems for more than two decades, but little progress has
      been made in developing more comprehensible report forms. Results are still
      reported in computer-generated printouts containing hundreds of numbers crowded
      into columns on each printed page. METHODS: We developed three software
      applications focusing on the graphic presentation of laboratory results. RESULTS:
      The first application summarizes data for a patient with a monoclonal gammopathy.
      The report provides a cumulative graphic presentation of
      immunofixation/electrophoresis data without any additional interpretation,
      focuses on a color-coded electrophoresis scan, and records up to 5 years on a
      single page. The second application deals with cerebrospinal fluid analysis. The
      report calculates relevant data and graphs the complex relationship between
      albumin and immunoglobulin results from paired serum and cerebrospinal fluid
      samples. Manually added interpretive text assures an output comprehensible to
      clinicians in all specialties. The third application produces a report
      summarizing quantitatively measured urinary marker protein profiles. The report
      form is generated by a flexible, completely user-definable knowledge-based
      system. It calculates numerous ratios and formulae, supports reflex testing,
      supplies an automated interpretation, and generates a specific graphic signature
      pattern of the results (MDI LabLink proteinuria differentiation). CONCLUSIONS:
      Increased clinical demand for graphically oriented report forms 5 years after
      their introduction has provided evidence that these reports transfer complex
      laboratory data and results to the clinician more effectively. The highest (more
      than threefold) increase in demand has been for reports for urinary marker
      protein profiles that feature a largely self-explanatory graphic signature
      pattern.

PMID- 12507960
TI  - Quantitative real-time PCR method for detection of B-lymphocyte monoclonality by
      comparison of kappa and lambda immunoglobulin light chain expression.
AB  - BACKGROUND: An abnormal IgLkappa:IgLlambda ratio has long been used as a clinical
      criterion for non-Hodgkin B-cell lymphomas. As a first step toward a quantitative
      real-time PCR-based multimarker diagnostic analysis of lymphomas, we have
      developed a method for determination of IgLkappa:IgLlambda ratio in clinical
      samples. METHODS: Light-up probe-based real-time PCR was used to quantify
      IgLkappa and IgLlambda cDNA from 32 clinical samples. The samples were also
      investigated by routine immunohistochemical analysis and flow cytometry. RESULTS:
      Of 32 suspected non-Hodgkin lymphoma samples analyzed, 28 were correctly assigned
      from real-time PCR measurements assuming invariant PCR efficiencies in the
      biological samples. Four samples were false negatives. One was a T-cell lymphoma,
      one was a diffuse large B-cell lymphoma, and one was reanalyzed and found
      lymphoma-positive by in situ calibration, which takes into account sample
      specific PCR inhibition. Twelve of the samples were fine-needle aspirates, and
      these were all correctly assigned. CONCLUSIONS: This work is a first step toward
      analyzing clinical samples by quantitative light-up probe-based real-time PCR.
      Quantitative real-time PCR appears suitable for high-throughput testing of
      cancers by measuring expression of tumor markers in fine-needle aspirates.

PMID- 12507962
TI  - Outcome validation of the Beckman Coulter access analyzer in a second-trimester
      Down syndrome serum screening application.
AB  - BACKGROUND: Mid-trimester maternal serum alpha-fetoprotein (AFP) and unconjugated
      estriol (uE3) are 30% lower and human chorionic gonadotropin (hCG) is twofold
      higher in Down syndrome pregnancies compared with unaffected pregnancies. In
      maternal serum screening, patient-specific risks are calculated using published
      gaussian frequency distribution parameters for these three markers obtained with
      previously available immunoassays. New immunoassays must generate similar
      distribution parameters if the accuracy of assigned risks and overall performance
      of prenatal screening are to be maintained. METHODS: Agreement between the
      Beckman Coulter Access and the Bayer Immuno 1 assays for AFP and hCG and the
      Amersham Amerlex-M RIA for uE3 was assessed in 558 fresh sera. Precision was
      measured over 6 weeks. Median concentrations were calculated by regression of 568
      Caucasian singleton pregnancy samples against gestational age in days. Frozen mid
      trimester sera from 44 confirmed Down syndrome singleton pregnancies (cases) were
      selected without conscious bias for reanalysis, and each case was matched with
      five control specimens from unaffected pregnancies. Serum markers were expressed
      as the multiple of the median (MoM) concentration derived from the control
      samples, corrected for maternal weight and converted to their log-equivalent
      values. Normality was assessed using probability plots and the Shapiro-Wilk W
      test. Gaussian distribution parameters were compared with established values, and
      Down syndrome risk calculations were assessed with a commonly used risk
      algorithm. RESULTS: The Access AFP and hCG assays had consistent proportional
      agreement with the established assays, whereas agreement between the uE3 methods
      was less consistent. Analytical imprecision was 3-6% at mid-trimester
      concentrations. Normal distributions were obtained for the log MoM values of all
      three markers in both the Down syndrome and unaffected populations, and their
      gaussian distribution parameters compared well with established values. The
      performance of the Access assays in an established trivariate risk algorithm for
      Down syndrome was equal to the performance exhibited by traditional methods.
      CONCLUSION: The Beckman Coulter Access analyzer provides valid mid-trimester
      serum AFP, uE3, and hCG results and risk assessments when applied in a prenatal
      Down syndrome screening service.

PMID- 12507961
TI  - C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal
      period: influence of illness severity, risk status, antenatal and perinatal
      complications, and infection.
AB  - BACKGROUND: Studies of the diagnostic accuracy of most laboratory tests for early
      onset neonatal sepsis have yielded variable results. We investigated whether some
      of this variation might be attributable to differences in population baseline
      severity and risk status as well as to specific ante- and perinatal variables,
      independent of the presence of neonatal infection. METHODS: The Score for
      Neonatal Acute Physiology (SNAP) was used to define illness severity, with SNAP
      Perinatal Extension (SNAP-PE) used to define the combined physiologic and
      perinatal mortality risk. A total of 134 ill newborns (19 with early-onset
      infection and 115 with no infection) were available for simultaneous analysis of
      the association of SNAP, SNAP-PE, and maternal and perinatal variables with C
      reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT)
      concentrations at birth and at 24 and 48 h of life. RESULTS: Early-onset neonatal
      infection was associated with significant increases in CRP, IL-6, and PCT
      concentrations at all three time points, independent of illness severity.
      However, among babies without infection, higher SNAP and SNAP-PE scores were
      associated with higher IL-6 concentrations at birth. Certain maternal or
      perinatal variables altered IL-6 and PCT values in the infected as well as in the
      uninfected neonates. However, if different cutoff points were used at any of the
      three neonatal ages, PCT sensitivity and specificity were greater than those of
      CRP or IL-6. CONCLUSIONS: Illness severity and risk status are unlikely to
      interfere with the use of CRP and PCT for detection of early-onset neonatal
      sepsis. In contrast, the diagnostic value of IL-6 at birth may be altered by
      physiologic severity and risk indexes. The reliability of CRP, IL-6, and PCT for
      the diagnosis of early-onset neonatal infection requires specific cutoff values
      for each evaluation time point over the first 48 h of life.

PMID- 12507963
TI  - Human kallikrein 13: production and purification of recombinant protein and
      monoclonal and polyclonal antibodies, and development of a sensitive and specific
      immunofluorometric assay.
AB  - BACKGROUND: The aims of this study were to develop immunologic reagents and a
      sensitive and specific immunoassay for human kallikrein 13 (hK13) and to examine
      the presence of hK13 in human tissues and biological fluids. METHODS: Recombinant
      hK13 protein was produced and purified with use of a Pichia pastoris yeast
      expression system. The protein was used as an immunogen to generate mouse
      monoclonal and rabbit polyclonal anti-hK13 antibodies. A sandwich-type
      immunoassay was developed with these antibodies. The assay was used to measure
      hK13 in various biological fluids and tissue extracts. Immunohistochemical
      analysis was also performed on nondiseased and cancerous prostatic sections.
      RESULTS: The hK13 immunoassay had a detection limit of 0.05 micro g/L and showed
      no cross-reactivity with homologous kallikreins. The assay was linear at 0-20
      micro g/L, and within-and between-run CVs were <10% (n = 12). hK13 was detected
      in tissues, including esophagus, tonsil, trachea, lung, cervix, and prostate.
      hK13 was also found in seminal plasma, amniotic fluid, follicular fluid, ascites
      of ovarian cancer patients, breast milk, and cytosolic extracts of ovarian cancer
      tissues. hK13 was immunohistochemically localized in epithelial cells of both
      nondiseased and cancerous prostate. hK13 appears to be overexpressed in 50% of
      ovarian cancer tissues compared with healthy ovarian tissues. Recovery of active
      enzyme added to milk or amniotic fluid was 70-98%, but was <20% when added to
      serum, suggesting rapid sequestration by protease inhibitors. In fluids and
      tissue extracts, hK13 was found in its free (approximately 30 kDa) form.
      CONCLUSIONS: This immunofluorometric assay for hK13 may be used to examine the
      value of hK13 as a disease biomarker and to further explore the physiologic and
      pathobiologic role of this enzyme in human disease.

PMID- 12507964
TI  - Human kallikrein 8: immunoassay development and identification in tissue extracts
      and biological fluids.
AB  - BACKGROUND: The serine protease human kallikrein 8 (hK8; neuropsin), a new member
      of the human kallikrein family, was predicted to be secreted; thus, it is
      expected to be present in biological fluids. The aim of this study was to develop
      a sensitive and specific immunoassay for hK8 (hK8-ELISA) and establish the
      distribution of hK8 in tissue extracts and biological fluids. METHODS:
      Recombinant hK8 was produced in a baculovirus expression system and purified with
      a three-step chromatographic procedure. Purified hK8 was injected into mice and
      rabbits for antibody generation. A highly specific and sensitive sandwich-type
      immunoassay (ELISA) was developed using the rabbit and mouse antisera to hK8. The
      hK8-ELISA was then used to study the distribution of hK8 in various biological
      fluids and tissue extracts. RESULTS: The dynamic range of the hK8-ELISA was 0.2
      (detection limit) to 20 micro g/L, and imprecision (CV) was <10% within this
      range. This hK8-ELISA was specific for hK8 and had no detectable cross-reactivity
      with other members of the human kallikrein family. With this assay, hK8 was
      detected in tissue extracts of esophagus (highest concentrations), skin, testis,
      tonsil, kidney, breast, and salivary gland and in the biological fluids breast
      milk (highest concentrations), amniotic fluid, seminal plasma, and serum.
      Furthermore, in some cancer cell lines, the concentration of hK8 was regulated by
      steroid hormones. CONCLUSIONS: We report for the first time production of
      recombinant hK8 protein, generation of antibodies, and development of a highly
      sensitive and specific immunoassay for quantification of hK8 in tissue extracts
      and biological fluids. This assay can be used to explore the potential of hK8 as
      a marker of cancer or other conditions.

PMID- 12507965
TI  - Dual-label immunoassay for simultaneous measurement of prostate-specific antigen
      (PSA)-alpha1-antichymotrypsin complex together with free or total PSA.
AB  - BACKGROUND: A major portion of prostate-specific antigen exists in circulation as
      a complex with alpha(1)-antichymotrypsin (PSA-ACT), whereas a minor part is free
      (fPSA). The proportion of PSA-ACT is increased in prostate cancer (PCa), but
      immunologic determination of PSA-ACT is hampered by a background produced by
      nonspecific adsorption of ACT to the solid phase. To reduce the nonspecific
      interference, we produced an antibody specific for complexed ACT and developed
      immunofluorometric assays (IFMAs) for simultaneous measurement of fPSA + PSA-ACT
      (fPSA/PSA-ACT) and PSA-ACT + total PSA (tPSA, PSA-ACT/tPSA). METHODS: Monoclonal
      antibodies (MAbs) were produced by immunization with PSA-ACT. The dual-label time
      resolved IFMAs for fPSA/PSA-ACT and PSA-ACT/tPSA used a capture MAb to tPSA, an
      Eu(3+)-labeled MAb to fPSA or complexed ACT, and an Sm(3+)-labeled MAb to
      complexed ACT or to tPSA as tracer antibodies. The clinical utility was evaluated
      using serum samples from individuals with or without PCa with PSA concentrations
      of 2.0-20.0 micro g/L. RESULTS: One MAb (1D10) showed low cross-reactivity with
      free ACT and cathepsin G-ACT. A sandwich assay for PSA-ACT with 1D10 as tracer
      had a detection limit of 0.05 micro g/L, and with this assay, PSA-ACT was
      undetectable in female sera. The detection limit for fPSA was 0.004 micro g/L.
      Determinations of the ratio of fPSA to PSA-ACT and the proportions of fPSA/tPSA
      and PSA-ACT/tPSA provided the same clinical specificity for PCa and provided
      significantly better clinical specificity than did tPSA. CONCLUSIONS: Background
      problems observed in earlier PSA-ACT assays are eliminated by the use of a MAb
      specific for complexed ACT as a tracer. The same clinical validity can be
      obtained by determination of fPSA or PSA-ACT together or in combination with
      tPSA.

PMID- 12507966
TI  - Quantitative analysis of tyrosine hydroxylase mRNA for sensitive detection of
      neuroblastoma cells in blood and bone marrow.
AB  - BACKGROUND: Sensitive monitoring of minimal residual disease may improve the
      treatment of neuroblastoma in children. To detect and monitor neuroblastoma cells
      in blood and bone marrow, we developed a quantitative method for the analysis of
      tyrosine hydroxylase mRNA. METHODS: We used real-time reverse transcription-PCR.
      The calibrator was constructed from a segment of tyrosine hydroxylase mRNA that
      included the target. Blood and bone marrow samples from 24 children with
      neuroblastoma and 1 child with ganglioneuroma were analyzed. Controls were blood
      samples from the cords of 40 babies, from 58 children 6 months to 15 years of
      age, and from 34 healthy adults, as well as from 12 children with other diseases.
      RESULTS: The detection limit was approximately 70 transcripts/mL. All 144 blood
      controls were below this limit. At diagnosis, blood tyrosine hydroxylase mRNA was
      higher in children with widespread disease (stage 4/4S; n = 6; range, 203-46,000
      transcripts/mL) than in patients with localized disease (stages 1-3; n = 6; </=83
      transcripts/mL; P = 0.002). Bone marrow from all five children with localized
      disease had concentrations <72 transcripts/mL, whereas five of six stage 4
      patients had increased concentrations (6,000-8,000,000 transcripts/mL; P <0.05).
      In nine children in whom tyrosine hydroxylase mRNA was measured repeatedly, the
      results corresponded to the clinical course. CONCLUSION: Quantitative analysis of
      tyrosine hydroxylase mRNA in blood and bone marrow is reliable and easy to
      perform and may be used for upfront staging, prognostic assessment, and treatment
      monitoring of neuroblastoma.

PMID- 12507967
TI  - Predictors of change in plasma total cysteine: longitudinal findings from the
      Hordaland homocysteine study.
AB  - BACKGROUND: Total cysteine (tCys) in plasma has recently been linked to
      cardiovascular risk and is also associated with cardiovascular risk factors,
      including body mass index (BMI) and cholesterol. Changes and predictors of change
      in tCys concentrations over a mean follow-up time of 6.0 (5.2-7.2) years were
      assessed in this study. METHODS: Baseline data from the Hordaland Homocysteine
      Study recorded in 1992-1993 included tCys, total homocysteine (tHcy), and various
      lifestyle and cardiovascular risk factors. In 1998-1999, the same measurements
      were repeated in 3,732 individuals born in 1950-1951 and 3,339 individuals born
      in 1925-1927. Most of the statistical analyses were done separately in the four
      age and sex groups. RESULTS: The overall mean values of tCys were higher at
      follow-up [mean (SD), 296 (41) micro mol/L] than at baseline [278 (36.5) micro
      mol/L]; P <0.0001. The mean percentage of increase in tCys in the different age
      and sex groups ranged from 4.9% to 8.5%. There was a significant correlation
      between the tCys values measured on the two occasions (Spearman correlation
      coefficient, 0.55-0.59 in the different age and sex groups; P <0.0001). The
      change in tCys correlated with changes in BMI, cholesterol, and diastolic blood
      pressure in the younger age group, whereas only changes in BMI predicted changes
      in tCys in the older age group. CONCLUSIONS: tCys increased in the 6 years
      between the two measurements. Factors related to the baseline tCys values,
      including BMI and the change in BMI, predicted the tCys changes over time.

PMID- 12507968
TI  - Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after
      controlled oral methamphetamine administration to human volunteers.
AB  - BACKGROUND: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200
      plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics
      and pharmacodynamics after oral administration of sustained-release METH.
      METHODS: Eight participants received four oral 10-mg S-(+)-METH hydrochloride
      sustained-release tablets within 7 days. Three weeks later, five participants
      received four oral 20-mg doses. Blood samples were collected for up to 24 h and
      oral fluid for up to 72 h after drug administration. RESULTS: After the first
      oral dose, initial plasma METH detection was within 0.25-2 h; c(max) was 14.5
      33.8 micro g/L (10 mg) and 26.2-44.3 micro g/L (20 mg) within 2-12 h. In oral
      fluid, METH was detected as early as 0.08-2 h; c(max) was 24.7-312.2 micro g/L
      (10 mg) and 75.3-321.7 micro g/L (20 mg) and occurred at 2-12 h. The median oral
      fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly
      variable. Neutral cotton swab collection yielded significantly higher METH and
      AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD)
      areas under the curve for AMP were 21% +/- 25% and 24% +/- 11% of those observed
      for METH in plasma and oral fluid, respectively. After a single low or high dose,
      plasma METH was >2.5 micro g/L for up to 24 h in 9 of 12 individuals (mean, 7.3
      +/- 5.5 micro g/L at 24 h); in oral fluid the detection window was at least 24 h
      (mean, 18.8 +/- 18.0 micro g/L at 24 h). The plasma and oral fluid 24-h METH
      detection rates were 54% and 60%, respectively. After four administrations, METH
      was measurable for 36-72 h (mean, 58.3 +/- 14.5 h). CONCLUSIONS: Perceived
      advantages of oral fluid for verifying METH exposure compared with urine include
      simpler specimen collection and reduced potential for adulteration, but urine
      offers higher analyte concentrations and a greater window of detection.

PMID- 12507969
TI  - Prevalence of fatty acid ethyl esters in meconium specimens.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBDs),
      and alcohol-related neurodevelopment disorders (ARNDs) in neonates are often the
      result of maternal alcohol consumption during pregnancy. Facial characteristics
      are associated with FAS, but ARBDs and ARNDs are more difficult to diagnose.
      Fetal exposure to alcohol can cause central nervous system dysfunction, pre- and
      postnatal growth problems, cardiac defects in neonates, and attention deficit
      disorders and mental retardation in older children. To date, diagnosis of fetal
      alcohol effect has depended largely on maternal interview, although clinical
      tests are becoming more widely used. Fatty acid ethyl esters (FAEEs) are formed
      in the body by esterification of ethanol with free fatty acids and trans
      esterification of glycerides and have been detected in the meconium of newborns.
      This report estimates the prevalence of fetal alcohol exposure in two populations
      by detecting FAEEs in meconium. METHODS: We analyzed the prevalence of FAEEs in
      the meconium of two separate groups of neonates by use of solid-phase extraction
      and analysis by gas chromatography-mass spectrometry in the chemical ionization
      mode. In the first study, meconium samples were taken anonymously from babies
      born in a large, regional perinatal center in Hawaii. In the second study,
      specimens were obtained from infants admitted to six different newborn intensive
      care units within the state of Utah. RESULTS: In the first study, 73 of 436
      (16.7%) meconium specimens tested were considered positive for FAEEs. When broken
      down into quartiles, the mean total FAEEs measured were 1,059, 3,133, 6,628, and
      62,115 ng/g. In the second study, 35 of 289 (12.1%) specimens were considered
      positive. When broken into quartiles, the mean total FAEEs were 1,139, 3,067,
      7,674, and 50,143 ng/g. The overall FAEE profiles of the two study sets were
      remarkably similar. CONCLUSION: In an adequate meconium specimen, a total FAEE
      concentration >10,000 ng/g may indicate that the newborn has been exposed to
      significant amounts of alcohol during pregnancy.

PMID- 12507970
TI  - Hemoglobin Gorwihl [alpha2beta(2)5(A2)Pro-->Ala], an electrophoretically silent
      variant with impaired glycation.
AB  - BACKGROUND: Some of the genetic variants of hemoglobin (Hb) and their chemically
      modified species are known to affect the measurement of Hb A(1c). The purpose of
      this study was to characterize Hb species in the blood sample of a 74-year-old
      German male with an exceptionally low Hb A(1c) value. METHODS: Hemolysates from
      the propositus and a healthy individual were analyzed by electrophoresis, cation
      exchange HPLC, boronate affinity chromatography, and electrospray ionization-mass
      spectrometry (ESMS). Genomic DNA was amplified by PCR, and the sequencing was
      performed on an ABI 310 sequencer. Functional properties of Hb were determined by
      oxygen equilibrium studies and CO recombination kinetics after flash
      photodissociation. Glycohemoglobin species were synthesized by incubating
      hemolysates with glucose. RESULTS: A novel, electrophoretically silent beta
      chain, beta5(A2)Pro-->Ala or Hb Gorwihl, was detected by cation-exchange HPLC. It
      accounted for approximately 44% of the total Hb and had functional properties
      similar to those of normal Hb A and a mild degree of heat instability. During
      incubation with glucose, glycation of the beta chains (assessed by ESMS) in the
      hemolysate of a healthy volunteer was twice as fast as in hemolysate from the
      propositus. CONCLUSIONS: The substitution beta5(A2)Pro-->Ala seems to affect
      neither the functional properties nor the heterotropic interactions of Hb, but
      slows glycation of the N-terminal valine by an unknown mechanism.

PMID- 12507971
TI  - Preparation and characterization of new WHO reference reagents for human
      chorionic gonadotropin and metabolites.
AB  - BACKGROUND: The currently used standards for human chorionic gonadotropin (hCG)
      and its alpha and beta subunits (hCGalpha and hCGbeta) contain substantial
      amounts of contaminating variants of hCG and other impurities. Furthermore, some
      partially degraded forms of hCG and its subunits have become of potential
      clinical importance, e.g., "nicked" forms of hCG (hCGn) and hCGbeta (hCGbetan),
      which contain cuts in the peptide backbone between amino acids 44-45 or 47-48 in
      hCGbeta, and a fragment of hCGbeta (hCGbetacf) consisting of amino acids 6-40 and
      55-92 bound together by disulfide bridges. The IFCC appointed a working group
      with the aim of preparing new standards for hCG and related substances to improve
      standardization of their immunoassays. METHODS: Large amounts of hCG and its
      subunits as well as of hCGn, hCGbetan, and hCGbetacf were prepared by previously
      developed purification methods in combination with hydrophobic interaction
      chromatography and reversed-phase HPLC. Each preparation was characterized on the
      basis of amino acid and sequence analyses, carbohydrate composition, and
      electrophoretic patterns. Immunoassays for relevant contaminating proteins were
      also performed. RESULTS: The major preparations were homogeneous and free of
      contaminating proteins. Concentrations of the final preparations were determined
      by amino acid analysis. CONCLUSIONS: Calibrated in substance concentrations
      (mol/L) based on amino acid analyses, these preparations will facilitate improved
      standardization of immunoassays for hCG and its metabolites. The six preparations
      have now been established by the WHO as new 1st Reference Reagents for
      immunoassays with the following codes: hCG 99/688, hCGbeta 99/650, hCGalpha
      99/720, hCGn 99/642, hCGbetan 99/692, and hCGbetacf 99/708. In contrast to the
      3rd International Standard (75/537), the clinically most important Reference
      Reagent for hCG (99/688) contains no hCGn and negligible amounts of free
      subunits.

PMID- 12507972
TI  - Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: a
      randomized placebo-controlled study.
AB  - BACKGROUND: Vitamin B(6) has attracted renewed interest because of its role in
      homocysteine metabolism and its possible relation to cardiovascular risk. We
      examined the plasma B(6) vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL),
      pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B(6)
      supplementation. METHODS: Patients (n = 90; age range, 38-80 years) undergoing
      coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin
      Intervention Trial) were allocated to the following daily oral treatment groups:
      (A), vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (B),
      vitamin B(12) and folic acid; (C), vitamin B(6); or (D), placebo. EDTA blood was
      obtained before treatment and 3, 14, 28, and 84 days thereafter. RESULTS: Before
      treatment, PLP (range, 5-111 nmol/L) and 4-PA (6-93 nmol/L) were the predominant
      B(6) vitamers identified in plasma. During the 84-day study period, the
      intraindividual variation (CV) in patients not treated with vitamin B(6) (groups
      B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of
      treatment, the increases in concentration were approximately 10-, 50-, and 100
      fold for PLP, 4-PA, and PL, respectively. No significant additional increase was
      observed at the later time points. The PLP concentration correlated to the
      concentrations of 4-PA and PL before treatment, but not after treatment. The PL
      concentration correlated with 4-PA before and after treatment. CONCLUSIONS:
      Vitamin B(6) treatment has an immediate effect on the concentrations and the
      forms of B(6) vitamers present in plasma, and the changes remain the same during
      prolonged treatment. Our results suggest that the B(6) vitamers in plasma reflect
      vitamin B(6) intake.

PMID- 12507973
TI  - Use of a major medical center clinical laboratory as a reference laboratory for a
      developing country: ordering patterns help set laboratory priorities.
AB  - BACKGROUND: The test menus for developed and developing countries may differ,
      depending on many factors, including the expected volume of testing, disease
      frequency and therapies available, clinical impact of the test, technical skill
      and equipment needed, cost, the patient population served, and whether
      alternative testing sites are available, and some of them may not be exactly
      known. We assessed test priorities in a developing country by making a broad
      range of tests available and then assessing which tests were actually used by the
      physicians in the country for the care of their patients. METHODS: The Barnes
      Jewish Hospital laboratory and Washington University Medical Center provided
      patients in the developing country of Eritrea access to the same tests as
      patients in St. Louis for all analytes that are stable at 4 degrees C, the lowest
      temperature that could be used for shipping. RESULTS: The use of the St. Louis
      laboratories increased steadily from 1998 to 2001. More than one-half of the
      physicians in Eritrea used the reference laboratories, with requests for thyroid
      function and female fertility representing 48-71% of the test requests over the 4
      years evaluated. The high degree of utilization for these test batteries was not
      predicted. Testing for thyroid function, female fertility, and lipid panels are
      now performed, or soon will be performed, in Eritrea based on the experience of
      the reference laboratory system. The reference laboratory system is continuing so
      that the test priorities of the country can be evaluated on an ongoing basis and
      specialized tests can be made available at a low cost. CONCLUSION: The
      experiences of a reference laboratory for a developing country can help to
      identify unanticipated priorities for medical testing within the country.

PMID- 12507974
TI  - Effect of androstenedione ingestion on plasma testosterone in young women; a
      dietary supplement with potential health risks.

PMID- 12507975
TI  - Comparison of five thrombin time reagents.

PMID- 12507976
TI  - Use of two biomarkers of renal ischemia to assess machine-perfused non-heart
      beating donor kidneys.

PMID- 12507977
TI  - Total iron-binding capacity calculated from serum transferrin concentration or
      serum iron concentration and unsaturated iron-binding capacity.

PMID- 12507978
TI  - Short-term variations in enterolactone in serum, 24-hour urine, and spot urine
      and relationship with enterolactone concentrations.

PMID- 12507979
TI  - Determination of D-mannose in plasma by HPLC.

PMID- 12507980
TI  - Use of the Architect-i2000 estradiol immunoassay during in vitro fertilization.

PMID- 12507981
TI  - Fast colorimetric method for measuring urinary iodine.

PMID- 12507982
TI  - Effects of midstream collection and the menstrual cycle on urine particles and
      dipstick urinalysis among healthy females.

PMID- 12507983
TI  - Sex and age differences in serum potassium in the United States.

PMID- 12507984
TI  - Serum CrossLaps compared with other markers of bone turnover in severely
      malnourished children before and after refeeding.

PMID- 12507985
TI  - Fetal cell-free plasma DNA concentrations in maternal blood are stable 24 hours
      after collection: analysis of first- and third-trimester samples.

PMID- 12507986
TI  - Quantification of mitochondrial DNA heteroplasmy by temporal temperature gradient
      gel electrophoresis.

PMID- 12507987
TI  - Problems with high-sensitivity C-reactive protein.

PMID- 12507988
TI  - Total protein determination in urine: aminoglycoside interference.

PMID- 12507989
TI  - New enzyme immunoassay for salivary cortisol.

PMID- 12507992
TI  - Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation,
      and cytoskeletal attachment.
AB  - Chicken embryo fibroblasts (CEFs) localize beta-actin mRNA to their lamellae, a
      process important for the maintenance of cell polarity and motility. The
      localization of beta-actin mRNA requires a cis localization element (zipcode) and
      involves zipcode binding protein 1 (ZBP1), a protein that specifically binds to
      the zipcode. Both localize to the lamellipodia of polarized CEFs. ZBP1 and its
      homologues contain two NH2-terminal RNA recognition motifs (RRMs) and four COOH
      terminal hnRNP K homology (KH) domains. By using ZBP1 truncations fused to GFP in
      conjunction with in situ hybridization analysis, we have determined that KH
      domains three and four were responsible for granule formation and cytoskeletal
      association. When the NH2 terminus was deleted, granules formed by the KH domains
      alone did not accumulate at the leading edge, suggesting a role for the NH2
      terminus in targeting transport granules to their destination. RNA binding
      studies were used to show that the third and fourth KH domains, not the RRM
      domains, bind the zipcode of beta-actin mRNA. Overexpression of the four KH
      domains or certain subsets of these domains delocalized beta-actin mRNA in CEFs
      and inhibited fibroblast motility, demonstrating the importance of ZBP1 function
      in both beta-actin mRNA localization and cell motility.

PMID- 12507993
TI  - Direct cadherin-activated cell signaling: a view from the plasma membrane.
AB  - Classical cadherin adhesion molecules are key determinants of cell recognition
      and tissue morphogenesis, with diverse effects on cell behavior. Recent
      developments indicate that classical cadherins are adhesion-activated signaling
      receptors. In particular, early-immediate Rac signaling is emerging as a
      mechanism to coordinate cadherin-actin integration at the plasma membrane.

PMID- 12507994
TI  - Imaging kinase--AKAP79--phosphatase scaffold complexes at the plasma membrane in
      living cells using FRET microscopy.
AB  - Scaffold, anchoring, and adaptor proteins coordinate the assembly and
      localization of signaling complexes providing efficiency and specificity in
      signal transduction. The PKA, PKC, and protein phosphatase-2B/calcineurin (CaN)
      scaffold protein A-kinase anchoring protein (AKAP) 79 is localized to excitatory
      neuronal synapses where it is recruited to glutamate receptors by interactions
      with membrane-associated guanylate kinase (MAGUK) scaffold proteins. Anchored PKA
      and CaN in these complexes could have important functions in regulating glutamate
      receptors in synaptic plasticity. However, direct evidence for the assembly of
      complexes containing PKA, CaN, AKAP79, and MAGUKs in intact cells has not been
      available. In this report, we use immunofluorescence and fluorescence resonance
      energy transfer (FRET) microscopy to demonstrate membrane cytoskeleton-localized
      assembly of this complex. Using FRET, we directly observed binding of CaN
      catalytic A subunit (CaNA) and PKA-RII subunits to membrane-targeted AKAP79. We
      also detected FRET between CaNA and PKA-RII bound simultaneously to AKAP79 within
      50 A of each other, thus providing the first direct evidence of a ternary kinase
      scaffold-phosphatase complex in living cells. This finding of AKAP-mediated PKA
      and CaN colocalization on a nanometer scale gives new appreciation to the level
      of compartmentalized signal transduction possible within scaffolds. Finally, we
      demonstrated AKAP79-regulated membrane localization of the MAGUK synapse
      associated protein 97 (SAP97), suggesting that AKAP79 functions to organize even
      larger signaling complexes.

PMID- 12507995
TI  - Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101
      phosphoinositide 3-kinase gamma.
AB  - Receptor-regulated class I phosphoinositide 3-kinases (PI3K) phosphorylate the
      membrane lipid phosphatidylinositol (PtdIns)-4,5-P2 to PtdIns-3,4,5-P3. This, in
      turn, recruits and activates cytosolic effectors with PtdIns-3,4,5-P3-binding
      pleckstrin homology (PH) domains, thereby controlling important cellular
      functions such as proliferation, survival, or chemotaxis. The class IB p110
      gamma/p101 PI3K gamma is activated by G beta gamma on stimulation of G protein
      coupled receptors. It is currently unknown whether in living cells G beta gamma
      acts as a membrane anchor or an allosteric activator of PI3K gamma, and which
      role its noncatalytic p101 subunit plays in its activation by G beta gamma. Using
      GFP-tagged PI3K gamma subunits expressed in HEK cells, we show that G beta gamma
      recruits the enzyme from the cytosol to the membrane by interaction with its p101
      subunit. Accordingly, p101 was found to be required for G protein-mediated
      activation of PI3K gamma in living cells, as assessed by use of GFP-tagged PtdIns
      3,4,5-P3-binding PH domains. Furthermore, membrane-targeted p110 gamma displayed
      basal enzymatic activity, but was further stimulated by G beta gamma, even in the
      absence of p101. Therefore, we conclude that in vivo, G beta gamma activates PI3K
      gamma by a mechanism assigning specific roles for both PI3K gamma subunits, i.e.,
      membrane recruitment is mediated via the noncatalytic p101 subunit, and direct
      stimulation of G beta gamma with p110 gamma contributes to activation of PI3K
      gamma.

PMID- 12508036
TI  - Evidence-based practice in dentistry: benefit or hindrance.

PMID- 12508037
TI  - The path from studying masticatory function to managing TMD and pain: a personal
      journey.

PMID- 12508038
TI  - Gene therapy for the treatment of oral squamous cell carcinoma.
AB  - Despite advances in surgery, radiotherapy, and chemotherapy, the survival of
      patients with oral squamous cell carcinoma has not significantly improved over
      the past several decades. Treatment options for recurrent or refractory oral
      cancers are limited. Gene therapy for oral cancer is currently under
      investigation in clinical trials. The goal of cancer gene therapy is to introduce
      new genetic material into target cells without toxicity to non-target tissues.
      This review discusses the techniques used in cancer gene therapy for oral
      squamous cell carcinoma and summarizes the ongoing strategies that are being
      evaluated in clinical trials.

PMID- 12508039
TI  - Cadherin-related neuronal receptors in incisor development.
AB  - Cadherins are cell adhesion molecules that are critical for tissue development.
      In this report, we identified members of the cadherin family cadherin-related
      neuronal receptors (CNRs) 1 and 5 expressed in rat incisors by the differential
      display method. Quantitative RT-PCR revealed that CNR1 mRNA is expressed in the
      secretory stage but reduced in the early-maturation stage, while CNR5 mRNA is
      expressed in both these stages. In situ hybridization showed that strong
      expression of CNR1 is strong in the secretory stage, but reduced in the early
      phase and diminished in the late phase of the early-maturation stage. CNR5 mRNA
      is expressed almost at the same levels in the secretory and in the early phase of
      the early-maturation stages but is absent in the late phase of the early
      maturation stage. Both CNR1 and 5 mRNA are continuously expressed in
      odontoblasts. Immunohistology showed that CNR proteins are expressed in the
      secretory and early-maturation stages of ameloblasts, but no protein expression
      at the late-maturation stage was observed. CNR proteins were continuously
      expressed in odontoblasts. We found that recombinant CNR1 binds dental epithelial
      and mesenchymal cells through N-terminal domain EC1 in vitro. These results
      suggest that CNR1 and CNR5 may play an important role in enamel and dentin
      formation, probably through cell-cell and/or cell-matrix interactions.

PMID- 12508040
TI  - Bone morphogenetic protein-2 inhibits differentiation and mineralization of
      cementoblasts in vitro.
AB  - As an approach for improving the outcome and predictability of periodontal
      regenerative therapies, we have focused on determining the responses of cells
      within the local environment to putative regenerative factors. This study
      examined the effects of bone morphogenetic protein-2 (BMP-2) on murine
      cementoblasts in vitro. Northern blot analysis indicated that BMP-2 decreased
      mRNA levels of bone sialoprotein and type I collagen dose-dependently (10-300
      ng/mL). At low doses, up to 100 ng/mL, BMP-2 had no effect on transcripts for
      osteocalcin and osteopontin, whereas at 300 ng/mL, BMP-2 greatly increased
      expression of these two genes. BMP-2 also inhibited cementoblast-mediated mineral
      nodule formation in a dose-dependent manner (inhibition was noted at 10 ng/mL).
      Noggin reversed the effects of BMP-2 on gene expression and on mineralization.
      These findings reflect the diverse responses of periodontal cells to BMP-2 and
      highlight the need to consider the complexity of factors involved in designing
      predictable regenerative therapies.

PMID- 12508041
TI  - Association between craniofacial growth and urinary bone metabolic markers
      (pyridinoline, deoxypyridinoline) in growing rats.
AB  - Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are intermolecular cross-links of
      mature collagen and reflect the bone turnover. The purpose of this study was to
      elucidate the association between craniofacial growth and urinary Pyr and Dpyr
      levels. Lateral cephalograms and 24-hour urine were taken for 7 male rats from 5
      to 20 wks old. The urinary Pyr and Dpyr were quantified by high-performance
      liquid chromatography. The neurocranium and upper viscerocranium exhibited
      significant increases in size, with the maximum rate at around 6 wks old. The
      mandible presented more substantial growth, with the maximum change at 8 wks old.
      The urinary Pyr and Dpyr levels gradually increased and reached the maximum at 8
      wks old. No prominent association was found between neurocranial growth and
      urinary levels of pyridinium cross-links, whereas Pyr and Dpyr levels exhibited
      similar time-dependent metabolic changes to mandibular growth. In conclusion, it
      is shown that urinary pyridinium cross-links may be useful for the prediction of
      mandibular growth.

PMID- 12508042
TI  - Role of K+ATP channels, endothelin A receptors, and effect of angiotensin II on
      blood flow in oral tissues.
AB  - K+(ATP) channels are involved in CGRP-mediated vasodilation and in the
      vasoconstriction induced by endothelin or angiotensin II. In this study, we
      examined the effects of a K+(ATP) channel antagonist and an ET(A) receptor
      antagonist on resting blood flow in the pulp and gingiva, and observed their role
      in the vasodilation induced by tooth stimulation. We also investigated whether
      receptors for angiotensin II exist in the pulp and gingiva. Blood flow was
      measured with laser-Doppler flowmetry. Under control conditions, the K+(ATP)
      channel antagonist and angiotensin II caused a significant drop in blood flow in
      both target tissues. Blocking of ET(A) receptor did not change basal blood flow.
      The vasodilation observed after tooth stimulation remained unchanged following
      blockade of K+(ATP) channels and ET(A) receptors. Analysis of the data shows that
      open K+(ATP) channels exist during resting conditions in the pulp and gingiva,
      but that CGRP seems to induce vasodilation mainly via mechanisms other than
      K+(ATP) channels. ET(A) and AT(1) receptors are found in the pulp and gingiva,
      but ET(A) receptors are not involved in modulation of a basal vascular tone in
      these tissues or in the vasodilation observed after tooth stimulation.

PMID- 12508043
TI  - Age effect on orthodontic tooth movement in rats.
AB  - Orthodontic procedures seem to be more time-consuming in adults than in
      juveniles. This might be related to delay in the initial tissue response or to a
      slower turnover of the bone and periodontal ligament in adults. To study this
      problem, we studied orthodontic tooth movement in two groups of 30 rats, aged 6
      wks and 9-12 mos, respectively. At one side of the maxilla, 3 molars together
      were moved mesially with a standardized orthodontic appliance delivering a force
      of 10 cN. The other side served as a control. The results showed a faster initial
      tooth movement in juvenile than in adult animals. However, once tooth movement
      had reached the linear phase, the rate of tooth movement was the same in both
      groups. The results indicate that, besides a delay in the onset of tooth movement
      in adult animals, tooth movement could be equally efficient in adults once it had
      started.

PMID- 12508044
TI  - Interaction between 2-ethoxybenzoic acid (EBA) and eugenol, and related changes
      in cytotoxicity.
AB  - The liquid of 2-ethoxybenzoic acid cements is composed of 2-ethoxybenzoic acid
      and eugenol (4-allyl-2-methoxyphenol). Recently, eugenol was reported to produce
      radicals at a higher pH, which consequently directly damages cells. We examined
      here whether eugenol radicals are generated from the mixture of eugenol/calcium
      hydroxide, and also whether 2-ethoxybenzoic acid or acetylsalicylic acid
      scavenges radicals, using electron spin resonance spectroscopy. Radicals were
      generated from the mixture of eugenol/calcium hydroxide in 50% dimethylsulfoxide
      solution. The radical intensity of eugenol in 50% dimethylsulfoxide with 0.1 M
      sodium bicarbonate buffer (pH 9.5) was dose-dependently reduced by 2
      ethoxybenzoic acid, whereas it was enhanced by acetylsalicylic acid. Next, we
      investigated the cytotoxic effect of eugenol on 2-ethoxybenzoic acid,
      acetylsalicylic acid, or calcium hydroxide on human pulp fibroblasts or a human
      submandibular gland cancer cell line. The cytotoxicity of EBA was decreased,
      whereas that of acetylsalicylic acid was increased by eugenol. In contrast, that
      of calcium hydroxide was not affected by eugenol. Human pulp fibroblast but not
      human submandibular gland cells showed a high resistance against calcium
      hydroxide. The generation of eugenol radicals in the liquid of 2-ethoxybenzoic
      acid cements caused by oxidation may be suppressed by 2-ethoxybenzoic acid.

PMID- 12508045
TI  - Long-term water-aging of whisker-reinforced polymer-matrix composites.
AB  - Long-term water exposure may degrade polymer-matrix composites. This study
      investigated the water-aging of whisker composites. It was hypothesized that
      whiskers would provide stable and substantial reinforcement, and that whisker
      type would affect water-aging resistance. Silica-fused Si(3)N(4) and SiC whiskers
      were incorporated into a resin. The specimens were tested by three-point flexure
      and nano-indentation vs. water-aging for 1 to 730 days. After 730 days, SiC
      composite had a strength (mean +/- SD; n = 6) of 185 +/- 33 MPa, similar to 146
      +/- 44 MPa for Si(3)N(4) composite (p = 0.064); both were significantly higher
      than 67 +/- 23 MPa for an inlay/onlay control (p < 0.001). Compared with 1 day,
      the strength of the SiC composite showed no decrease, while that of the Si(3)N(4)
      composite decreased. The decrease was due to whisker weakening rather than to
      resin degradation or interface breakdown. Whisker composites also had higher
      moduli than the controls. In conclusion, silica-fused whiskers bonded to polymer
      matrix and resisted long-term water attack, resulting in much stronger composites
      than the controls after water-aging.

PMID- 12508046
TI  - The effects of mandibular two-implant overdentures on nutrition in elderly
      edentulous individuals.
AB  - It is unclear whether mandibular implant overdentures improve the nutritional
      state of edentulous patients better than conventional dentures. In a randomized
      clinical trial, we tested for post-treatment differences in nutritional status
      between patients with mandibular two-implant retained overdentures and those with
      conventional complete dentures. Edentulous subjects (ages 65-75 yrs) received two
      implant mandibular overdentures (IOD, n = 30) or conventional dentures (CD, n =
      30). Measures of nutritional state were gathered before and 6 mos after
      treatment. Significant improvements in anthropometric parameters were detected in
      the IOD but not in the CD group, for percent body fat (p = 0.011) and skin-fold
      thickness at the biceps, subscapularis, and abdomen (p < 0.05), with significant
      decreases in waist circumference (p < 0.0001) and waist-hip ratio (p = 0.001).
      Significant increases were seen in concentrations of serum albumin (p = 0.015),
      hemoglobin (p = 0.01), and B12 (p = 0.01). No significant between-group
      differences were found. These results suggest that low-cost IOD treatment may
      improve the nutritional state of edentulous people.

PMID- 12508047
TI  - Quality of marginal adaptation evaluation of posterior composites in clinical
      trials.
AB  - The evaluation of margins of restorations in clinical trials relies on the
      subjective assessment of evaluators, with no instrument having been developed,
      let alone validated, to assist in the process. The purpose of the present study
      was to assess the quality of evaluations of marginal adaptation by analyzing the
      distribution of marginal steps rated according to clinical criteria. Replicas of
      435 restorations, the marginal qualities of which had been evaluated according to
      modified USPHS criteria, were randomly selected from the Occlusin multi-center
      clinical trial program. The marginal step height in the most deteriorated area of
      each restoration was measured by means of a digital step-height instrument. An
      overlap between the steps in the restorations with A (Alfa; replacement
      unnecessary) and B (Bravo; replacement questionable) ratings was found to be in
      the range of 101 microm to 321 microm. When the steps with a height greater or
      less than one standard deviation of the mean were excluded, the overlap was
      reduced to a range of 168 micro m to 173 microm. This finding indicates a
      marginal height boundary between A and B ratings for marginal adaptation of 170
      +/- 3 microm.

PMID- 12508048
TI  - Fluorosis development in seven age cohorts after an 11-month break in water
      fluoridation.
AB  - This study used an 11-month break in water fluoridation to identify the time when
      developing incisors are most sensitive to fluorosis development. The study was
      based in Durham, NC, where an interruption to water fluoridation occurred between
      September, 1990, and August, 1991. A total of 1896 children was dentally
      examined. Fluorosis was measured by the TF index, and parents or guardians
      completed a questionnaire on demographics and fluoride history. Age cohorts
      ranged from those born 5 years before the break, to those born 1 year after the
      resumption of fluoridation. Fluorosis prevalence for seven age cohorts whose
      birth years ranged from 1985-86 to 1991-92 was 57.1, 62.3, 33.0, 32.3, 39.8,
      30.2, and 36.8%, respectively. Children aged from birth to 3 years at the break,
      and those born 1 year after it, had less fluorosis than those aged 4-5 years at
      the break.

PMID- 12508050
TI  - Dihydropyridine receptors as voltage sensors for a depolarization-evoked, IP3R
      mediated, slow calcium signal in skeletal muscle cells.
AB  - The dihydropyridine receptor (DHPR), normally a voltage-dependent calcium
      channel, functions in skeletal muscle essentially as a voltage sensor, triggering
      intracellular calcium release for excitation-contraction coupling. In addition to
      this fast calcium release, via ryanodine receptor (RYR) channels, depolarization
      of skeletal myotubes evokes slow calcium waves, unrelated to contraction, that
      involve the cell nucleus (Jaimovich, E., R. Reyes, J.L. Liberona, and J.A.
      Powell. 2000. Am. J. Physiol. Cell Physiol. 278:C998-C1010). We tested the
      hypothesis that DHPR may also be the voltage sensor for these slow calcium
      signals. In cultures of primary rat myotubes, 10 micro M nifedipine (a DHPR
      inhibitor) completely blocked the slow calcium (fluo-3-fluorescence) transient
      after 47 mM K(+) depolarization and only partially reduced the fast Ca(2+)
      signal. Dysgenic myotubes from the GLT cell line, which do not express the
      alpha(1) subunit of the DHPR, did not show either type of calcium transient
      following depolarization. After transfection of the alpha(1) DNA into the GLT
      cells, K(+) depolarization induced slow calcium transients that were similar to
      those present in normal C(2)C(12) and normal NLT cell lines. Slow calcium
      transients in transfected cells were blocked by nifedipine as well as by the G
      protein inhibitor, pertussis toxin, but not by ryanodine, the RYR inhibitor.
      Since slow Ca(2+) transients appear to be mediated by IP(3), we measured the
      increase of IP(3) mass after K(+) depolarization. The IP(3) transient seen in
      control cells was inhibited by nifedipine and was absent in nontransfected
      dysgenic cells, but alpha(1)-transfected cells recovered the depolarization
      induced IP(3) transient. In normal myotubes, 10 micro M nifedipine, but not
      ryanodine, inhibited c-jun and c-fos mRNA increase after K(+) depolarization.
      These results suggest a role for DHPR-mediated calcium signals in regulation of
      early gene expression. A model of excitation-transcription coupling is presented
      in which both G proteins and IP(3) appear as important downstream mediators after
      sensing of depolarization by DHPR.

PMID- 12508051
TI  - On the mechanism of MgATP-dependent gating of CFTR Cl- channels.
AB  - CFTR, the product of the gene mutated in cystic fibrosis, is an ATPase that
      functions as a Cl(-) channel in which bursts of openings separate relatively long
      interburst closed times (tauib). Channel gating is controlled by phosphorylation
      and MgATP, but the underlying molecular mechanisms remain controversial. To
      investigate them, we expressed CFTR channels in Xenopus oocytes and examined, in
      excised patches, how gating kinetics of phosphorylated channels were affected by
      changes in [MgATP], by alterations in the chemical structure of the activating
      nucleotide, and by mutations expected to impair nucleotide hydrolysis and/or
      diminish nucleotide binding affinity. The rate of opening to a burst (1/tauib)
      was a saturable function of [MgATP], but apparent affinity was reduced by
      mutations in either of CFTR's nucleotide binding domains (NBDs): K464A in NBD1,
      and K1250A or D1370N in NBD2. Burst duration of neither wild-type nor mutant
      channels was much influenced by [MgATP]. Poorly hydrolyzable nucleotide analogs,
      MgAMPPNP, MgAMPPCP, and MgATPgammaS, could open CFTR channels, but only to a
      maximal rate of opening approximately 20-fold lower than attained by MgATP acting
      on the same channels. NBD2 catalytic site mutations K1250A, D1370N, and E1371S
      were found to prolong open bursts. Corresponding NBD1 mutations did not affect
      timing of burst termination in normal, hydrolytic conditions. However, when
      hydrolysis at NBD2 was impaired, the NBD1 mutation K464A shortened the prolonged
      open bursts. In light of recent biochemical and structural data, the results
      suggest that: nucleotide binding to both NBDs precedes channel opening; at
      saturating nucleotide concentrations the rate of opening to a burst is influenced
      by the structure of the phosphate chain of the activating nucleotide; normal,
      rapid exit from bursts occurs after hydrolysis of the nucleotide at NBD2, without
      requiring a further nucleotide binding step; if hydrolysis at NBD2 is prevented,
      exit from bursts occurs through a slower pathway, the rate of which is modulated
      by the structure of the NBD1 catalytic site and its bound nucleotide. Based on
      these and other results, we propose a mechanism linking hydrolytic and gating
      cycles via ATP-driven dimerization of CFTR's NBDs.

PMID- 12508052
TI  - Dequalinium: a novel, high-affinity blocker of CNGA1 channels.
AB  - Cyclic nucleotide-gated (CNG) channels have been shown to be blocked by
      diltiazem, tetracaine, polyamines, toxins, divalent cations, and other compounds.
      Dequalinium is an organic divalent cation which suppresses the rat small
      conductance Ca(2+)-activated K(+) channel 2 (rSK2) and the activity of protein
      kinase C. In this study, we have tested the ability of dequalinium to block CNGA1
      channels and heteromeric CNGA1+CNGB1 channels. When applied to the intracellular
      side of inside-out excised patches from Xenopus oocytes, dequalinium blocks CNGA1
      channels with a K(1/2) approximately 190 nM and CNGA1+CNGB1 channels with a
      K(1/2) approximately 385 nM, at 0 mV. This block occurs in a state-independent
      fashion, and is voltage dependent with a zdelta approximately 1. Our data also
      demonstrate that dequalinium interacts with the permeant ion probably because it
      occupies a binding site in the ion conducting pathway. Dequalinium applied to the
      extracellular surface also produced block, but with a voltage dependence that
      suggests it crosses the membrane to block from the inside. We also show that at
      the single-channel level, dequalinium is a slow blocker that does not change the
      unitary conductance of CNGA1 channels. Thus, dequalinium should be a useful tool
      for studying permeation and gating properties of CNG channels.

PMID- 12508053
TI  - TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions.
AB  - Trace metal ions such as Zn(2+), Fe(2+), Cu(2+), Mn(2+), and Co(2+) are required
      cofactors for many essential cellular enzymes, yet little is known about the
      mechanisms through which they enter into cells. We have shown previously that the
      widely expressed ion channel TRPM7 (LTRPC7, ChaK1, TRP-PLIK) functions as a
      Ca(2+)- and Mg(2+)-permeable cation channel, whose activity is regulated by
      intracellular Mg(2+) and Mg(2+).ATP and have designated native TRPM7-mediated
      currents as magnesium-nucleotide-regulated metal ion currents (MagNuM). Here we
      report that heterologously overexpressed TRPM7 in HEK-293 cells conducts a range
      of essential and toxic divalent metal ions with strong preference for Zn(2+) and
      Ni(2+), which both permeate TRPM7 up to four times better than Ca(2+). Similarly,
      native MagNuM currents are also able to support Zn(2+) entry. Furthermore, TRPM7
      allows other essential metals such as Mn(2+) and Co(2+) to permeate, and permits
      significant entry of nonphysiologic or toxic metals such as Cd(2+), Ba(2+), and
      Sr(2+). Equimolar replacement studies substituting 10 mM Ca(2+) with the
      respective divalent ions reveal a unique permeation profile for TRPM7 with a
      permeability sequence of Zn(2+) approximately Ni(2+) >> Ba(2+) > Co(2+) > Mg(2+)
      >/= Mn(2+) >/= Sr(2+) >/= Cd(2+) >/= Ca(2+), while trivalent ions such as La(3+)
      and Gd(3+) are not measurably permeable. With the exception of Mg(2+), which
      exerts strong negative feedback from the intracellular side of the pore, this
      sequence is faithfully maintained when isotonic solutions of these divalent
      cations are used. Fura-2 quenching experiments with Mn(2+), Co(2+), or Ni(2+)
      suggest that these can be transported by TRPM7 in the presence of physiological
      levels of Ca(2+) and Mg(2+), suggesting that TRPM7 represents a novel ion-channel
      mechanism for cellular metal ion entry into vertebrate cells.

PMID- 12508054
TI  - Influence of permeant ions on gating in cyclic nucleotide-gated channels.
AB  - Cyclic nucleotide-gated channels are key components in the transduction of visual
      and olfactory signals where their role is to respond to changes in the
      intracellular concentration of cyclic nucleotides. Although these channels poorly
      select between physiologically relevant monovalent cations, the gating by cyclic
      nucleotide is different in the presence of Na(+) or K(+) ions. This property was
      investigated using rod cyclic nucleotide-gated channels formed by expressing the
      subunit 1 (or alpha) in HEK293 cells. In the presence of K(+) as the permeant
      ion, the affinity for cGMP is higher than the affinity measured in the presence
      of Na(+). At the single channel level, subsaturating concentrations of cGMP show
      that the main effect of the permeant K(+) ions is to prolong the time channels
      remain open without major changes in the shut time distribution. In addition, the
      maximal open probability was higher when K(+) was the permeant ion (0.99 for K(+)
      vs. 0.95 for Na(+)) due to an increase in the apparent mean open time. Similarly,
      in the presence of saturating concentrations of cAMP, known to bind but unable to
      efficiently open the channel, permeant K(+) ions also prolong the time channels
      visit the open state. Together, these results suggest that permeant ions alter
      the stability of the open conformation by influencing of the O-->C transition.

PMID- 12508055
TI  - Starch: the need for improved quality or quantity--an overview.
AB  - Starch is one of the most important plant products to man. It is an essential
      component of food providing a large proportion of the daily calorific intake and
      is important in non-food uses such as in adhesives. However, while much is known
      about the chemistry and pathways of synthesis for starch, there are major gaps in
      this knowledge so that it is not possible to modify the quantity or quality of
      starch produced by plants in a predictable way. While yield has improved markedly
      over the last century it is no longer improving faster than the growth in
      population and, at the same time, farmers' incomes in Europe have been falling,
      especially in the UK. Thus, production, even in Europe, is not much greater than
      demand. In the western world an increasing amount of the harvested crop is
      processed and, therefore, the quality of the raw product becomes an increasingly
      important issue. There is, therefore, an increasing need to combine the modern
      mathematical modelling tools with modern biochemical tools and the modern science
      of genomics.

PMID- 12508056
TI  - Regulation of sucrose to starch conversion in growing potato tubers.
AB  - Growing potato tubers have been used as a model system to investigate the
      regulation of starch synthesis. Results indicate that sucrose degradation and
      starch synthesis are controlled via regulatory signals in response to sucrose and
      oxygen availability. (i) Sucrose leads to a co-ordinated up-regulation of sucrose
      synthase and ADP-glucose phosphorylase at the transcriptional and post
      transcriptional level. Transcriptional regulation of ADP-glucose phosphorylase
      leads to rapid changes in transcript levels, but relatively slow changes in
      protein levels. The rapid regulation of this enzyme in response to sucrose is
      mediated by a novel mechanism, involving redox-activation of ADPGlc
      pyrophosphorylase. Sucrose synthase is regulated via transcriptional regulation,
      but again the resulting changes in enzyme activity occur relatively slowly. More
      rapid changes in the flux of this enzyme follow due to rapid changes in the
      levels of uridine nucleotides. (ii) Internal oxygen concentrations fall to low
      levels in growing tubers, triggering a restriction of respiration, a decrease in
      the adenylate energy status, and a widespread decrease in metabolic and
      biosynthetic activity. These metabolic adaptations will allow oxygen consumption
      to be decreased and prevent the tissue from becoming anoxic. It will be discussed
      how these factors interact at different levels and different time-scales of
      control to regulate tuber metabolism in response to physiological and
      environmental inputs.

PMID- 12508057
TI  - Metabolic signalling and carbon partitioning: role of Snf1-related (SnRK1)
      protein kinase.
AB  - A protein kinase that plays a key role in the global control of plant carbon
      metabolism is SnRK1 (sucrose non-fermenting-1-related protein kinase 1), so
      called because of its homology and functional similarity with sucrose non
      fermenting 1 (SNF1) of yeast. This article reviews studies on the
      characterization of SnRK1 gene families, SnRK1 regulation and function,
      interacting proteins, and the effects of manipulating SnRK1 activity on carbon
      metabolism and development.

PMID- 12508058
TI  - Decreased sucrose content triggers starch breakdown and respiration in stored
      potato tubers (Solanum tuberosum).
AB  - To change the hexose-to-sucrose ratio within phloem cells, yeast-derived
      cytosolic invertase was expressed in transgenic potato (Solanum tuberosum cv.
      Desiree) plants under control of the rolC promoter. Vascular tissue specific
      expression of the transgene was verified by histochemical detection of invertase
      activity in tuber cross-sections. Vegetative growth and tuber yield of transgenic
      plants was unaltered as compared to wild-type plants. However, the sprout growth
      of stored tubers was much delayed, indicating impaired phloem-transport of
      sucrose towards the developing bud. Biochemical analysis of growing tubers
      revealed that, in contrast to sucrose levels, which rapidly declined in growing
      invertase-expressing tubers, hexose and starch levels remained unchanged as
      compared to wild-type controls. During storage, sucrose and starch content
      declined in wild-type tubers, whereas glucose and fructose levels remained
      unchanged. A similar response was found in transgenic tubers with the exception
      that starch degradation was accelerated and fructose levels increased slightly.
      Furthermore, changes in carbohydrate metabolism were accompanied by an elevated
      level of phosphorylated intermediates, and a stimulated rate of respiration.
      Considering that sucrose breakdown was restricted to phloem cells it is concluded
      that, in response to phloem-associated sucrose depletion or hexose elevation,
      starch degradation and respiration is triggered in parenchyma cells. To study
      further whether elevated hexose and/or hexose-phosphates or decreased sucrose
      levels are responsible for the metabolic changes observed, sucrose content was
      decreased by tuber-specific expression of a bacterial sucrose isomerase. Sucrose
      isomerase catalyses the reversible conversion of sucrose into palatinose, which
      is not further metabolizable by plant cells. Tubers harvested from these plants
      were found to accumulate high levels of palatinose at the expense of sucrose. In
      addition, starch content decreased slightly, while hexose levels remained
      unaltered, compared with the wild-type controls. Similar to low sucrose
      containing invertase tubers, respiration and starch breakdown were found to be
      accelerated during storage in palatinose-accumulating potato tubers. In contrast
      to invertase transgenics, however, no accumulation of phosphorylated
      intermediates was observed. Therefore, it is concluded that sucrose depletion
      rather than increased hexose metabolism triggers reserve mobilization and
      respiration in stored potato tubers.

PMID- 12508059
TI  - Balancing supply and demand: the spatial regulation of carbon metabolism in grass
      and cereal leaves.
AB  - Leaf primary metabolism responds to changes in both supply of inputs and demand
      for products. Metabolic control in leaves changes both spatially and temporally.
      Using leaves of C(3) temperate Gramineae, the spatial control of carbohydrate
      metabolism has been studied using a range of approaches. Single-cell sampling and
      subsequent analysis of metabolites, proteins and transcripts has indicated
      significant differences between epidermal, mesophyll and parenchymatous bundle
      sheath cells. These differences correlate with differentiated function as
      heterotrophic, autotrophic and transport pathway components of the leaf. The
      review emphasizes the key role of sucrose and discusses its catabolism to hexoses
      and its anabolism to fructans as mechanisms for the preservation of sucrose
      gradients within the leaf.

PMID- 12508060
TI  - Genetic approaches to understanding sugar-response pathways.
AB  - Plants as photoautotrophic organisms are able to produce the carbohydrates they
      require and have developed mechanisms to co-ordinate carbohydrate production and
      its metabolism. Carbohydrate-derived signals regulate the expression of genes
      involved in both photosynthesis and metabolism, and control carbohydrate
      partitioning. A number of genetic approaches have been initiated to understand
      sugar-response pathways in plants and identify the components involved. Screening
      strategies to date have been based on the effects of high sugar media on early
      seedling development or on changes in the enzyme activity or expression of sugar
      responsive genes. These screens have established roles for plant hormones in
      sugar-response pathways, in particular for abscisic acid. The present emphasis on
      the role of plant hormones in sugar responses is due to the fact that mutants
      could be readily identified as belonging to these established pathways, but also
      results from the nature of the mutant screens in use. Progress is being made on
      the identification of mutants and genes that may be specific to sugar-signalling
      pathways. It is also expected that the modification of existing screens may
      target sugar-signalling pathways more directly. Genetic approaches may be
      especially useful in identifying components of novel signalling pathways unique
      to plants, and their combination with genomic and molecular approaches will guide
      future research.

PMID- 12508061
TI  - Differentiation of legume cotyledons as related to metabolic gradients and
      assimilate transport into seeds.
AB  - Legume seed development is closely related to metabolism and nutrient transport.
      To analyse this relationship, a combination of biochemical, histological and
      transgenic approaches was used. Sugars within tissue sections have been
      quantitatively measured by metabolic imaging. During cotyledon differentiation
      glucose gradients emerge related to a particular cell type, with higher
      concentrations in non-differentiated premature regions. Sucrose in creases at the
      beginning of maturation in a layer underneath the outer epidermis expressing a
      sucrose transporter. Sucrose distribution is initially controlled by uptake
      activity and the permeability within the parenchyma and, later on, also by
      differences in growth and starch accumulation. Increased sucrose levels are
      accompanied by increased levels of sucrose synthase and ADP-Glc pyrophosphorylase
      mRNAs, but carbon flux into starch is initially still low. Rates increase at a
      stage when hexose concentrations become low, allowing increased flux through the
      sucrose synthase pathway. Transfer cell formation represents a regional
      specification of the cotyledonary epidermis for embryo nutrition characterized by
      increased transport-active cell surfaces and up-regulated expression of transport
      related genes. The E2748 pea seed mutation blocks epidermal differentiation into
      transfer cells and leads to the loss of epidermal cell identity. Embryos with
      impaired epidermis cannot tolerate elevated levels of sucrose and respond with
      disorganized growth. The E2748 gene product is required for transfer cell
      formation in developing cotyledons with no other function during plant growth.
      Seed coat permeability provides a hypoxic environment for embryo development.
      However, at maturity, seed energy supply is not limited indicating fundamental
      developmental and metabolic adaptations. Results from transgenic seeds show that
      altered expression of single genes induces complex and unexpected changes. In AGP
      antisense seeds the block in starch synthesis leads to pleiotropic effects of
      water and nitrogen content and induces temporal changes in seed development.

PMID- 12508062
TI  - Extracellular invertase: key metabolic enzyme and PR protein.
AB  - Extracellular invertase is the key enzyme of an apoplasmic phloem unloading
      pathway and catalyses the hydrolytic cleavage of the transport sugar sucrose
      released into the apoplast. This mechanism contributes to long-distance
      assimilate transport, provides the substrate to sustain heterotrophic growth and
      generates metabolic signals known to effect various processes of primary
      metabolism and defence responses. The essential function of extracellular
      invertase for supplying carbohydrates to sink organs was demonstrated by the
      finding that antisense repression of an anther-specific isoenzyme provides an
      efficient method for metabolic engineering of male sterility. The regulation of
      extracellular invertase by all classes of phytohormones indicates an essential
      link between the molecular mechanism of phytohormone action and primary
      metabolism. The up-regulation of extracellular invertase appears to be a common
      response to various biotic and abiotic stress-related stimuli such as pathogen
      infection and salt stress, in addition to specific stress-related reactions.
      Based on the observed co-ordinated regulation of source/sink relations and
      defence responses by sugars and stress-related stimuli, the identified activation
      of distinct subsets of MAP kinases provides a mechanism for signal integration
      and distribution within such complex networks. Sucrose derivatives not
      synthesized by higher plants, such as turanose, were shown to elicit responses
      distinctly different from metabolizable sugars and are rather perceived as stress
      related stimuli.

PMID- 12508063
TI  - Roles of cell-wall invertases and monosaccharide transporters in the growth and
      development of Arabidopsis.
AB  - The hydrolysis of sucrose by cell-wall invertases (cwINV) and the subsequent
      import of hexoses into target cells appears to be crucial for appropriate
      metabolism, growth and differentiation in plants. Hexose uptake from the apoplast
      is catalysed by monosaccharide/H+ symporters (Sugar Transport Proteins or STPs),
      which have the potential to sense sugars. Import of extracellular hexoses may
      generate signals to orchestrate cellular activities, or simply feed metabolic
      pathways distinct from those fed by sucrose. It is predicted that Arabidopsis has
      six cwINV genes and at least 14 STP genes. These genes show different spatial and
      temporal patterns of expression, and several knock-out mutants have been isolated
      for analysis. AtSTP1 transports glucose, galactose, xylose, and mannose, but not
      fructose. It accounts for the majority of the AtSTP activity in vegetative
      tissues and its activity is markedly repressed by treatment with exogenous
      sugars. These observations are consistent with a role in the retrieval of cell
      wall-derived sugars, for example, during carbohydrate limitation or cell
      expansion. The AtSTP1 gene is also expressed in developing seeds, where it might
      be responsible for the uptake of glucose derived from imported sucrose. The large
      number of AtcwINV and AtSTP genes, together with complex patterns of expression
      for each, and the possibility that each protein may have more than one
      physiological function, provides the plant with the potential for a multiplicity
      of patterns of monosaccharide utilization to direct growth and differentiation or
      to respond flexibly to changing environmental conditions.

PMID- 12508064
TI  - Is trehalose-6-phosphate a regulator of sugar metabolism in plants?
AB  - It has recently emerged that many higher plants can synthesize trace amounts of
      trehalose. In arabidopsis disruption of the first step of trehalose synthesis,
      catalysed by trehalose-6-phosphate synthase (TPS), has lethal consequences,
      demonstrating an important physiological role. It is not yet clear what the
      precise function of trehalose synthesis is, but there is mounting evidence that
      trehalose-6-phosphate is implicated in the regulation of sugar metabolism.
      Further work is necessary to confirm this hypothesis and determine the underlying
      mechanism.

PMID- 12508065
TI  - Carbon metabolite feedback regulation of leaf photosynthesis and development.
AB  - Photosynthesis is regulated as a two-way process. Light regulates the expression
      of genes for photosynthesis and the activity of the gene products (feedforward
      control). Rate of end-product use down-stream of the Calvin cycle, determined
      largely by nutrition and temperature, also affects photosynthetic activity and
      photosynthetic gene expression (feedback control). Whereas feedforward control
      ensures efficient light use, feedback mechanisms ensure that carbon flow is
      balanced through the pathways that produce and consume carbon, so that inorganic
      phosphate is recycled and nitrogen is distributed optimally to different
      processes to ensure growth and survival. Actual mechanisms are sketchy and
      complex, but carbon to nitrogen balance rather than carbon status per se is
      central to understanding carbon metabolite feedback control of photosynthesis. In
      addition to determining the activity of the metabolic machinery, carbon
      metabolite feedback mechanisms also regulate photosynthesis at the leaf level
      through the regulation of leaf development. This review summarizes the current
      sketchy, but growing, knowledge of the mechanisms through which carbon metabolite
      feedback mechanisms regulate leaf photosynthesis.

PMID- 12508066
TI  - Fructan biosynthesis in transgenic plants.
AB  - Data from plants transformed to accumulate fructan are assessed in the context of
      natural concentrations of reserve carbohydrates and natural fluxes of carbon in
      primary metabolism: Transgenic fructan accumulation is universally reported as an
      instantaneous endpoint concentration. In exceptional cases, concentrations of 60
      160 mg g(-1) fresh mass were reported and compare favourably with naturally
      occurring maximal starch and fructan content in leaves and storage organs.
      Generally, values were less than 20 mg g(-1) for plants transformed with
      bacterial genes and <9 mg g(-1) for plant-plant transformants. Superficially, the
      results indicate a marked modification of carbon partitioning. However,
      transgenic fructan accumulation was generally constitutive and involved
      accumulation over time-scales of weeks or months. When calculated as a function
      of accumulation period, fluxes into the transgenic product were low, in the range
      0.00002-0.03 nkat g(-1). By comparison with an estimated minimum daily
      carbohydrate flux in leaves for a natural fructan-accumulating plant in field
      conditions (37 nkat g(-1)), transgenic fructan accumulation was only 0.00005
      0.08% of primary carbohydrate flux and does not indicate radical modification of
      carbon partitioning, but rather, a quantitatively minor leakage into transgenic
      fructan. Possible mechanisms for this low fructan accumulation in the
      transformants are considered and include: (i) rare codon usage in bacterial genes
      compared with eukaryotes, (ii) low transgene mRNA concentrations caused by low
      expression and/or high turnover, (iii) resultant low expression of enzyme
      protein, (iv) resultant low total enzyme activity, (v) inappropriate kinetic
      properties of the gene products with respect to substrate concentrations in the
      host, (vi) in situ product hydrolysis, and (vii) levan toxicity. Transformants
      expressing bacterial fructan synthesis exhibited a number of aberrant phenotypes
      such as stunting, leaf bleaching, necrosis, reduced tuber number and mass, tuber
      cortex discoloration, reduction in starch accumulation, and chloroplast
      agglutination. In severe cases of developmental aberration, potato tubers were
      replaced by florets. Possible mechanisms to explain these aberrations are
      discussed. In most instances, the attempted subcellular targeting of the
      transgene product was not demonstrated. Where localization was attempted, the
      transgene product generally mis-localized, for example, to the cell perimeter or
      to the endomembrane system, instead of the intended target, the vacuole.
      Fructosyltransferases exhibited different product specificities in planta than in
      vitro, expression in planta generally favouring the formation of larger fructan
      oligomers and polymers. This implies a direct influence of the intracellular
      environment on the capacity for polymerization of fructosyltransferases and may
      have implications for the mechanism of natural fructan polymerization in vivo.

PMID- 12508067
TI  - Starch synthesis and carbon partitioning in developing endosperm.
AB  - The biosynthesis of starch is the major determinant of yield in cereal grains. In
      this short review, attention is focused on the synthesis of the soluble substrate
      for starch synthesis, ADPglucose (ADPG). Consideration is given to the pathway of
      ADPG production, its subcellular compartmentation, and the role of metabolite
      transporters in mediating its delivery to the site of starch synthesis. As ADPG
      is an activated sugar, the dependence of its production on respiration, changes
      which occur during development, and the constraints which ATP production may
      place on carbon partitioning into different end-products are discussed.

PMID- 12508068
TI  - Starch mobilization in leaves.
AB  - Starch mobilization is well understood in cereal endosperms, but both the pathway
      and the regulation of the process are poorly characterized in other types of
      plant organs. Arabidopsis leaves offer the opportunity for rapid progress in this
      area, because of the genomic resources available in this species and the ease
      with which starch synthesis and degradation can be monitored and manipulated.
      Progress in understanding three aspects of starch degradation is described: the
      role of disproportionating enzyme, the importance of phosphorolytic degradation,
      and new evidence about the involvement of a starch-phosphorylating enzyme in the
      degradative process. Major areas requiring further research are outlined.

PMID- 12508069
TI  - Markers and signals associated with nitrogen assimilation in higher plants.
AB  - A key concept underpinning current understanding of the carbon/nitrogen (C/N)
      interaction in plants is that the capacity for N assimilation is aligned to
      nutrient availability and requirements by the integrated perception of signals
      from hormones, nitrate, sugars, organic acids, and amino acids. Studies on the
      nature and integration of these signals over the last ten years has revealed a
      complex network of controls brokered by an interplay of C and N signals. These
      controls not only act to orchestrate the relative rates of C and N assimilation
      and carbohydrate and amino acid production, but they also have a significant
      influence on plant development. Amino acids are the hub around which the
      processes of N assimilation, associated C metabolism, photorespiration, export of
      organic N from the leaf, and the synthesis of nitrogenous end-products revolve.
      Since specific major amino acids or their relative ratios are modulated
      differentially by photorespiration and N assimilation, even though these
      processes are tightly intermeshed, they are potentially powerful markers for
      metabolite profiling and metabolomics approaches to the study of plant biology.
      Moreover, while minor amino acids show marked diurnal rhythms, their contents
      fluctuate in a co-ordinated manner. It is probable that factors associated with
      early events and processes in C and N assimilation influence the relative
      composition of minor amino acids.

PMID- 12508070
TI  - Function and specificity of 14-3-3 proteins in the regulation of carbohydrate and
      nitrogen metabolism.
AB  - Protein phosphorylation is key to the regulation of many proteins. Altered
      protein activity often requires the interaction of the phosphorylated protein
      with a class of "adapters" known as 14-3-3 proteins. This review will cover
      aspects of 14-3-3 interaction with key proteins of carbon and nitrogen metabolism
      such as nitrate reductase, glutamine synthetase and sucrose-phosphate synthase.
      It will also address 14-3-3 involvement in signal transduction pathways with
      emphasis on the regulation of plant metabolism. To date, 14-3-3 proteins have
      been identified and studied in many diverse systems, yielding a plethora of data,
      requiring careful analysis and interpretation. Problems such as these are not
      uncommon when dealing with multigene families. The number of isoforms makes the
      question of redundancy versus specificity of 14-3-3 proteins a crucial one. This
      issue is discussed in relation to structure, function and expression of 14-3-3
      proteins.

PMID- 12508072
TI  - Nutrient requirements in preterm infants.

PMID- 12508073
TI  - The genetics of childhood disease and development.

PMID- 12508074
TI  - Genomics and pediatric research.

PMID- 12508075
TI  - The bone disease of preterm birth: a biomechanical perspective.
AB  - The bone disease of preterm birth has traditionally been explained by a decrease
      in bone formation from insufficient availability of calcium and phosphorus.
      However, there is emerging evidence that there is increased bone resorption in
      the bone disease of preterm birth, an observation that indicates some other
      explanation for this condition. The biomechanical model of postnatal bone
      formation states that, through a regulatory feedback system in the bone called
      the mechanostat, bone is able to respond to increased bone loading by increasing
      bone strength and to decreased bone loading by decreasing bone strength. It is
      suggested that this increased bone resorption in the markedly preterm infant
      compared with the term infant is secondary to decreased bone loading. Application
      of this model to the fetus and preterm infant suggests that intrauterine bone
      loading of the fetus from movement and kicking against the uterus is critical for
      normal fetal bone formation. The associated muscle growth from this activity also
      contributes to bone loading. The markedly preterm infant is deprived of much of
      this critical time period of intrauterine bone accretion, and bone formation
      occurs in the less favorable extrauterine environment, where there is
      significantly less bone loading.

PMID- 12508076
TI  - Fetal DNA in maternal plasma/serum: the first 5 years.

PMID- 12508077
TI  - Quantitative analysis of male fetal DNA in maternal serum of gravid rhesus
      monkeys (Macaca mulatta).
AB  - The isolation of human fetal DNA from the maternal circulation has provided a
      source of fetal material for prenatal diagnosis. The objective of this study was
      to investigate whether a similar pattern could be observed in the maternal
      circulation of male-bearing gravid rhesus monkeys. A real-time PCR TaqMan system
      for the rhesus Y-chromosome sex determining region was used to determine fetal
      sex and to quantify fetal DNA concentrations. Results in 14 healthy pregnancies
      indicated that fetal male DNA could be routinely detected in maternal serum by 50
      d of gestation (late first trimester; term 165 +/- 10 d). Fetal DNA
      concentrations increased with advancing gestation, reaching a mean of 341 genome
      equivalents/mL of serum (range 11-1570 copies/mL) in the last trimester of
      gestation, similar to findings in humans. The fetal DNA concentration
      corresponded to 2.7% of the total maternal serum DNA in the third trimester.
      Similar to findings in humans, male fetal DNA sequences were not detected
      postpartum (through 4 wk postpartum) or in animals with a previous history of
      delivering male offspring. These data indicate that fetal male DNA is present in
      the maternal circulation of gravid rhesus monkeys comparable to findings in
      humans and further support the use of this nonhuman primate species as a model to
      investigate fetomaternal cell trafficking and microchimerism.

PMID- 12508078
TI  - Effect of low versus high intravenous amino acid intake on very low birth weight
      infants in the early neonatal period.
AB  - Greater protein intakes are required than have been commonly used to achieve
      fetal in utero protein accretion rates in preterm neonates. To study the efficacy
      and safety of more aggressive amino acid intake, we performed a prospective
      randomized study in 28 infants [mean wt, 946 +/- 40 g (SEM)] of 1 (low amino acid
      intake, LAA) versus 3 g.kg(-1).d(-1) (high amino acid intake, HAA) at 52.0 +/-
      3.0 h of life. After a minimum of 12 h of parenteral nutrition, efficacy was
      determined by protein balance and was significantly lower in the LAA versus HAA
      groups by both nitrogen balance (-0.26 +/- 0.11 versus 1.16 +/- 0.15 g.kg(-1).d(
      1), p < 0.00005) and leucine stable isotope (0.184 +/- 0.17 versus 1.63 +/- 0.20
      g.kg(-1).d(-1), p < 0.0005) methods. Leucine flux and oxidation and nonoxidative
      leucine disposal rates were all significantly higher in the HAA versus LAA groups
      (249 +/- 13 versus 164 +/- 8, 69 +/- 5 versus 32 +/- 3, and 180 +/- 10 versus 132
      +/- 8 micro mol.kg(-1).h(-1), respectively, p < 0.005), but leucine appearance
      from protein breakdown was not (140 +/- 15 in HAA versus 128 +/- 8 micro mol.kg(
      1).h(-1)). In terms of possible toxicity with HAA, there were no significant
      differences between groups in the amount of sodium bicarbonate administered,
      degree of acidosis as determined by base deficit, or blood urea nitrogen
      concentration. Parenteral HAA versus LAA intake resulted in increased protein
      accretion, primarily by increasing protein synthesis versus suppressing protein
      breakdown, and appeared to be well tolerated by very preterm infants in the first
      days of life.

PMID- 12508079
TI  - Effect of short-term fasting on bone elongation rates: an analysis of catch-up
      growth in young male rats.
AB  - Bone elongation in the postnatal animal is a result of cellular activity during
      endochondral ossification. Growth plate chondrocytes undergo a differentiation
      cascade involving stem cell clonal expansion and cellular enlargement during
      hypertrophy. Nutritional status has a significant effect on rates of bone growth,
      and a period of accelerated growth will occur if nutritional stunting of growth
      in early childhood can be corrected. This study focuses on changes in rates of
      increase in bone length in a model of catch-up growth in 4-wk-old male rats.
      Animals fasted for 3 d reached a weight approximately 60% of the control
      littermates. By 28 d postfasting, fasted animals had regained weight to 95% of
      control levels. A 3-d fast caused an immediate and profound decrease in rate of
      growth in the proximal tibial growth plate to only 30% of that of control
      animals, while stopping growth in the distal tibial growth plate. During the
      rapid initial rate acceleration of bone elongation, growth rate in both growth
      plates reached that of the control littermates by 7 d postfasting. The proximal
      tibial growth plate then maintained rates that were 10-15% higher than control
      over the rest of the experimental period. By 10 d postfasting, the previously
      fasted animals were on the same weight/rate trajectory as the control
      littermates. Changes in elongation rates were reflected by dramatic changes in
      growth plate morphology in all cellular zones. This is the first study to
      directly correlate weight recovery during catch-up with growth rate responses at
      the level of the growth plate.

PMID- 12508080
TI  - Developmental expression of heme oxygenase in the rat lung.
AB  - Heme oxygenase (HO), the rate-limiting enzyme in the formation of bilirubin, is
      expressed in the lung and may serve as an antioxidant. This enzyme results in the
      formation of antioxidant bile pigments and the degradation of pro-oxidant heme.
      We wanted to evaluate the differences in expression of HO-1, the inducible form,
      and HO-2, the constitutive isoenzyme, during lung maturation and document whether
      lung HO expression was similar to that of other antioxidant enzymes. Lung total
      HO activity and HO-1 and HO-2 proteins as well as HO-1 and HO-2 mRNA were
      evaluated in animals from 16 d of gestation (e(16.5)) to 2 mo of age. Heme
      content was also evaluated because heme is the substrate of the reaction. HO-1
      mRNA was maximal at e(19.5) and e(20.5), whereas HO-2 mRNA was not changed
      throughout maturation. Lung HO-1 protein was highest on the first days of life
      and lowest in adults, whereas HO-2 protein was maximally expressed at postnatal d
      5 and then declined to reach adult values. As to HO activity, there was a
      prenatal peak at e(20.5), a second lesser peak at d 5, and thereafter a decline
      to adult values. Lung heme content was inversely correlated with HO activity or
      protein as the highest heme values were seen in adults with the lowest HO
      activity. In response to hyperoxia, HO-1 mRNA was induced only in the adult
      lungs. A better understanding of the maturational regulation of lung HO will
      define a role for HO in newborns at risk for oxygen toxicity.

PMID- 12508081
TI  - Pulmonary effects of triiodothyronine (T3) and hydrocortisone (HC)
      supplementation in preterm infants less than 30 weeks gestation: results of the
      THORN trial--thyroid hormone replacement in neonates.
AB  - The THORN trial was a multicenter, randomized, double-blind, placebo-controlled
      clinical trial to test the hypothesis that administration of triiodothyronine
      (T(3)) and hydrocortisone would decrease mortality and respiratory morbidity in
      preterm infants of less than 30 wk gestation. Two hundred fifty-three infants
      were randomized to receive either 6 micro g.kg(-1).d(-1) of T(3) with 1 mg.kg(
      1).d(-1) of hydrocortisone or 5% dextrose (placebo) as a continuous i.v. infusion
      for 7 d. The dose was halved on d 5. Our first primary outcome was death or
      ventilator dependence at 1 wk, and the second was death or oxygen dependence at 2
      wk. The overall mortality rate for both groups was 11.4%. Relative risk of death
      or ventilator dependence at 1 wk, treated versus placebo, was 0.87, p = 0.2, and
      death or oxygen dependence at 2 wk, 1.00, p = 0.9. We examined the relationship
      between free T(3) (FT(3)) and free thyroxine (FT(4)) levels in the first 7 d and
      the primary outcome death or ventilator dependence at 1 wk in all 253 babies. We
      found significant positive correlations of p = 0.05 for FT(3) and p = 0.002 for
      FT(4). Thus the higher the FT(3) and FT(4) levels, the better the outcome. No
      beneficial effects of T(3) and hydrocortisone were shown. In this study, although
      FT(3) levels were doubled by the treatment infusion, FT(4) levels were
      significantly suppressed. The lack of any beneficial effect of T(3) in our study
      may be explained by suppression of FT(4) in the treatment group.

PMID- 12508082
TI  - Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic
      brain injury in rats, assessed by auditory brainstem response.
AB  - A method to assess long-term neurofunctional outcome of hypothermia on immature
      brains has not yet been clearly established. To investigate the effects of
      hypothermia on long-term neurofunctional outcome, we studied brainstem function
      using auditory brainstem response in adult rats after neonatal hypoxic-ischemic
      brain injury. Seven-day-old rats underwent a combination of left common carotid
      artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17). The rats
      were divided into three groups: hypothermia group (n = 6), normothermia group (n
      = 6), and sham control group (n = 5). During recovery from the hypoxic-ischemic
      insult, body temperature was reduced to 30 degrees C for 24 h in the hypothermia
      group, but was kept at 37 degrees C in the normothermia and sham control group.
      Three months later the rats were assessed by auditory brainstem response, then
      killed. The normothermia group showed increased III-V latencies and wave V
      abnormalities. Hypothermia significantly ameliorated wave V abnormalities. Injury
      to the ipsilateral inferior colliculus was also reduced in the hypothermia group
      compared with that in the normothermia group, and the degree of damage assessed
      histologically correlated well with auditory brainstem response findings. The
      current study demonstrates that postischemic hypothermia may provide effective
      and long-lasting neurofunctional as well as histopathologic protection to the
      immature brain.

PMID- 12508083
TI  - Deficient brain RNA polymerase and altered nucleolar structure persists until day
      8 after perinatal asphyxia of the rat.
AB  - RNA polymerases (POL) are integral constituents of the protein synthesis
      machinery, with POL I and POL III coding for ribosomal RNA and POL II coding for
      protein. POL I is located in the nucleolus and transcribes class I genes, those
      that code for large ribosomal RNA. It has been reported that the POL system is
      seriously affected in perinatal asphyxia (PA) immediately after birth. Because
      POL I is necessary for protein synthesis and brain protein synthesis was shown to
      be deranged after hypoxic-ischemic conditions, we aimed to study whether POL
      derangement persists in a simple, well-documented animal model of graded global
      PA at the activity, mRNA, protein, and morphologic level until 8 d after the
      asphyctic insult. Nuclear POL I activity was determined according to a
      radiochemical method; mRNA steady state and protein levels of RPA4O-an essential
      subunit of POL I and III-were evaluated by blotting methods; and the POL I
      subunit polymerase activating factor-53 was evaluated using immunohistochemistry.
      Silver staining and transmission electron microscopy were used to examine the
      nucleolus. At the eighth day after PA, nuclear POL I decreased with the length of
      the asphyctic period, whereas mRNA and protein levels for RPA4O were unchanged.
      The subunit polymerase activating factor-53, however, was unambiguously reduced
      in several brain regions. Dramatic changes of nucleolar morphology were observed,
      the main finding being nucleolar disintegration at the electron microscopy level.
      We suggest that severe acidosis and/or deficient protein kinase C in the brain
      during the asphyctic period may be responsible for disintegration of the
      nucleolus as well as for decreased POL activity persisting until the eighth day
      after PA. The biologic effect may be that PA causes impaired RNA and protein
      synthesis, which has been already observed in hypoxic-ischemic states.

PMID- 12508084
TI  - Effects of neonatal high-dose short-term glucocorticoid treatment on the lung: a
      morphologic and morphometric study in the rat.
AB  - Glucocorticoids are often applied in neonatology and perinatology to fight the
      problems of respiratory distress and chronic lung disease. There are, however,
      many controversies regarding the adverse side effects and long-term clinical
      benefits of this therapeutic approach. In rats, glucocorticoids are known to
      seriously impair the formation of alveoli when applied during the first two
      postnatal weeks even at very low dosage. The current study investigates short
      term and long-term glucocorticoid effects on the rat lung by means of morphologic
      and morphometric observations at light and electron microscopic levels.
      Application of a high-dosage protocol for only few days resulted in a marked
      acceleration of lung development with a precocious microvascular maturation
      resulting in single capillary network septa in the first 4 postnatal days. By
      postnatal d 10, the lung morphologic phenotype showed a step back in the
      maturational state, with an increased number of septa with double capillary
      layer, followed by an exceptional second round of the alveolarization process. As
      a result of this process, there was an almost complete recovery in the
      parenchymal lung structure by postnatal d 36, and by d 60, there were virtually
      no qualitative or quantitative differences between experimental and control rats.
      These findings indicate that both dosage and duration of glucocorticoid therapy
      in the early postnatal period are very critical with respect to lung development
      and maturation and that a careful therapeutic strategy can minimize late sequelae
      of treatment.

PMID- 12508085
TI  - Perfluorochemical (PFC) combinations for acute lung injury: an in vitro and in
      vivo study in juvenile rabbits.
AB  - Perfluorochemical (PFC) fluids of different physical properties were titrated and
      tested in vitro for physical properties that are appropriate for respiratory
      application. Two PFC liquids were studied: perfluoromethylcyclohexane (PP2), a
      liquid with high vapor pressure and low viscosity, and perfluoromethyldecalin
      (PP9), a fluid with low vapor pressure and high viscosity. Eighteen rabbits (2.05
      +/- 0.07 kg; mean +/- SEM) were lung-lavaged and randomized: group I, control
      group; group II, partial liquid ventilation with 75% PP2 and 25% PP9; group III,
      partial liquid ventilation with 50% PP2 and 50% PP9; and group IV, partial liquid
      ventilation with 25% PP2 and 75% PP9. Ventilator volumes were kept constant
      during the 4-h experiment. Cardiopulmonary measurements were performed every 30
      min. The lung histology was examined. The in vitro study showed PFC
      [viscosity/vapor pressure (in cS and mm Hg, respectively)] as follows: 100% PP2
      (0.88/141); 100% PP9 (3.32/2.9); 75% PP2 and 25% PP9 (1.26/107); 50% PP2 and 50%
      PP9 (1.63/13.7); and 25% PP2 and 75% PP9 (2.21/4.4). The in vivo experiments
      found that combinations of moderate vapor pressure (groups 3 and 4) demonstrated
      good gas exchange, compliance, and histologic findings. Thus, combinations of PFC
      liquids can be formulated to modulate the physiologic outcome in acutely injured
      lungs, and may prove useful for alternative PFC liquid applications.

PMID- 12508086
TI  - Cardiovascular fluctuations and transfer function analysis in stable preterm
      infants.
AB  - To examine the baroreceptor reflex function, a beat-to-beat analysis between
      systolic blood pressure (SBP) and R-R interval fluctuations was studied in 10
      stable appropriate-for-gestational age preterm infants (range, 27.2-33.7 wk) in
      the first postnatal week during quiet sleep. Spectral power analysis, using fast
      Fourier transform, and transfer functions (gain and phase difference) between SBP
      and R-R fluctuations were estimated in a low-frequency band (LF, 0.03-0.2 Hz) and
      high-frequency band (HF defined as the frequency band between the 10th and 90th
      centiles of the individual respiratory frequency). The LF/HF ratio reflects the
      sympathovagal balance. The mean frequency (+/-SD) of LF peaks was centered at
      0.07 +/- 0.02 Hz. The mean frequency (+/-SD) of the individual HF band was 0.82
      +/- 0.21 Hz. The LF/HF ratio in the R-R interval series [median, 29;
      interquartile range (IQR), 16-40] was higher than in the SBP series (median, 8;
      IQR, 4-14). The gain between R-R interval and SBP fluctuations (median, 4.2 ms/mm
      Hg; IQR, 2.4-5.0) in the LF band was higher than in the HF band (median, 1.7
      ms/mm Hg; IQR, 1.4-3.0). SBP fluctuations lead R-R interval fluctuations in the
      LF band with a median phase difference of +96 degrees (IQR, 67-132). At LF the
      fluctuations in SBP precede changes in R-R interval with a time delay of 3.8 s.
      These observations indicate a dominant role of the sympathetic system in stable
      preterm infants in comparison with published adult values. Cross-spectral
      analysis allows a test for tracking the development of the sympathetic system in
      neonates.

PMID- 12508087
TI  - A placebo-controlled comparison of effects of repetitive doses of betamethasone
      and dexamethasone on lung maturation and lung, liver, and body weights of mouse
      pups.
AB  - The aim of this study was to compare in vivo effects of single and repetitive
      doses of betamethasone (BETA) and dexamethasone (DEX) administered to pregnant
      mice on lung maturation and lung, liver, and body weights (LLBW) of their pups.
      One hundred and eighty gravid Swiss albino mice were randomly assigned to 1 of 6
      groups (n = 30) and administered either BETA, DEX, or saline as a single dose at
      14 d gestation or repetitive doses twice daily at 14 and 15 d gestation. All the
      study groups were then divided into three sets (n = 10). The mice in the second
      sets were redivided into three subsets randomly (including four, three, and three
      mice). All gestations in the first sets were terminated at 16.5 d gestation to
      observe the neonatal breathing pattern (scale to 0-5; 5 is unlabored breathing)
      of male and female pups whereas other sets had normal delivery. The pups in
      first, second, and third sets were killed for evaluation in the first set after
      the evaluation of breathing pattern, in the subsets of second set on postnatal d
      1, 3, and 5, and in the third set on postnatal d 90. We recorded maternal body
      weights at 0 and 16.5 d gestation, and LLBW, the lung/body weight ratio of pups,
      sex, and the amount of live and dead births per litter. Pups exposed to BETA and
      DEX had significantly lower maternal weight compared with the saline groups. The
      death litter size was significantly higher in pups exposed to repetitive doses of
      DEX than the other treatments. Sex had no significant effect on breathing score
      and LLBW. Pups exposed to repetitive doses of BETA and DEX presented a higher
      breathing score than the other groups. The breathing score was significantly
      higher with BETA than DEX after their repetitive use. The LLBW were significantly
      less in the treatment groups, especially in the group exposed to repetitive doses
      of DEX. In conclusion, repetitive doses of BETA and DEX lead to increased fetal
      lung maturation, but this may be at the expense of fetal and neonatal growth. DEX
      is less potent in accelerating lung maturation than BETA but it causes more
      reduction in fetal and neonatal growth.

PMID- 12508088
TI  - Impaired cardiorespiratory recovery after laryngeal stimulation in nicotine
      exposed young lambs.
AB  - The hypothesis that postnatal nicotine exposure weakens cardiorespiratory
      recovery from reflex apnea and bradycardia was tested in eight lambs continuously
      infused with nicotine from the day of birth at a dose of 1 to 2 mg.kg(-1).d(-1).
      Eight age-matched lambs infused with saline served as controls. Apnea and
      bradycardia were elicited by laryngeal stimulation with 1 mL of water (laryngeal
      chemoreflex) both during air breathing [0.21 fraction of inspired oxygen
      (FiO(2))] and mild hypoxia (0.10 FiO(2)) at a mean postnatal age of 5 +/- 1, 14
      +/- 1, and 28 +/- 1 d. Ventilation, heart rate, and blood pressure were similar
      in the two groups at rest. In response to laryngeal chemoreflex stimulation,
      nicotine-treated lambs had a more pronounced decrease in ventilation (p < 0.05),
      longer reflex apnea (p < 0.001 in 0.21 FiO(2); p < 0.01 in 0.10 FiO(2)), and
      greater reflex bradycardia (p < 0.01). During reflex apnea, sighs were less
      efficient in restoring heart rate to prestimulation level, and a greater decrease
      in heart rate was observed before sighs in nicotine-treated lambs. These effects
      were most apparent at 5 d of age, when nicotine-treated lambs also had lower
      ventilation during hypoxia (p < 0.05). The response to hyperoxia was comparable
      in the two groups at all ages. The ability to terminate laryngeal chemoreflex
      induced apnea is attenuated in young lambs continuously exposed to nicotine. This
      attenuation is present both in normoxia and in hypoxia and is accompanied by
      reduced effects from sighing on cardiac autoresuscitation.

PMID- 12508089
TI  - Nicotinic induction of preproenkephalin and tyrosine hydroxylase gene expression
      in butyrate-differentiated rat PC12 cells: a model for adaptation to gut-derived
      environmental signals.
AB  - Accelerated maturation of peripheral sympathoadrenal transmitter levels and
      function occurs at 7-10 postnatal days in the rat. This event is temporally
      disconnected from the timing of major changes in physiologic stimuli evident
      after the birthing process (i.e. temperature, oxygen, sound, light, etc.).
      Colonization of the gut, fermentation of carbohydrates, and production of short
      chain fatty acids (e.g. butyrate) mirrors this postnatal time course. In this
      report, we examined the interaction between butyrate differentiation of rat
      pheochromocytoma cells and cholinergic-nicotinic induction of the neuropeptide
      (enkephalin) and catecholamine-related biosynthetic enzymes (tyrosine
      hydroxylase, dopamine beta-hydroxylase, phenylethanolamine N-methyltransferase).
      Our results show that butyrate induces both preproenkephalin and tyrosine
      hydroxylase mRNA through a proximal promoter region and that this regulatory step
      is time and dose dependent. Moreover, there is an additional interaction with
      cholinergic-nicotinic inducible mechanisms consistent with classically described
      transsynaptic cholinergic regulation of these genes. Dopamine beta-hydroxylase
      and phenylethanolamine N-methyltransferase promoters were not affected by
      butyrate treatment. We speculate that colonization of the human gut (along with
      the attendant fermentation of enteral carbohydrates to short-chain fatty acids)
      may represent a mechanism through which environmental signals affect postnatal
      maturation of sympathoadrenal transmitter systems.

PMID- 12508090
TI  - Effect of maternal smoking on fetal catecholamine concentrations at birth.
AB  - The aim of this study was to compare catecholamine concentrations in the fetal
      umbilical artery cord blood from the offspring of smokers versus the offspring of
      nonsmokers. Pregnant women who were self-identified as smokers (>/=10 cigarettes
      per day throughout pregnancy) or nonsmokers were recruited for study
      participation. Maternal blood was collected for cotinine concentrations.
      Umbilical artery cord blood was collected at delivery for arterial pH and
      catecholamine concentrations. Cord blood was obtained from 51 subjects, including
      21 smokers and 30 nonsmokers. Median epinephrine concentrations [304 pg/mL versus
      597 pg/mL (Mann-Whitney U = 170; p = 0.006)] and median norepinephrine
      concentrations [3148 pg/mL versus 6558 pg/mL (Mann-Whitney U = 191; p = 0.006)]
      were significantly lower in smokers compared with nonsmokers, respectively. After
      controlling for gestational age, route of delivery, and arterial pH, log
      transformed epinephrine concentrations between smokers and nonsmokers were
      statistically significant (p = 0.03), with a similar trend for log-transformed
      norepinephrine concentrations (p = 0.07). Analyses of the data using cotinine <20
      ng/mL to classify nonsmokers also showed differences in epinephrine
      concentrations between groups (p = 0.02). These results are consistent with
      results from animal studies showing that catecholamine concentrations may be
      affected by prenatal nicotine exposure. Further studies are needed to validate
      these findings and to examine the specific mechanism by which these differences
      may arise.

PMID- 12508091
TI  - Heterogous dystrophin mRNA produced by a novel splice acceptor site mutation in
      intermediate dystrophinopathy.
AB  - The molecular background of an intermediate type of dystrophinopathy [Duchenne
      and Becker muscular dystrophy (DMD/BMD)] remains to be clarified, and out-of 
      frame and in-frame mutations of the dystrophin gene are shown to be causes of DMD
      and BMD, respectively. In a boy with this disease, dystrophin mRNA extracted from
      lymphocytes and muscle were analyzed both qualitatively and quantitatively using
      reverse transcription PCR. Three different dystrophin mRNA were found to be
      produced via the use of three cryptic splice acceptor sites resulting from a
      novel point mutation of 2831-2A>G at the conserved splice acceptor site of intron
      20. One of three mRNA showed an insertion of six nucleotides of intron 20 between
      exons 20 and 21 (dys+6) that encoded two novel amino acids in the rod domain of
      dystrophin. Two other mRNA species showed an insertion of seven nucleotides of
      intron 20 between exons 20 and 21 (dys+7) or a seven-nucleotide deletion in exon
      21 (dys-7). Quantitative analysis of each dystrophin mRNA expressed in the boy's
      skeletal muscle disclosed that around 95% and 5% of dystrophin mRNAs were dys-7
      and dys+6, respectively, whereas these two mRNA were almost equally expressed in
      lymphocytes. It is suggested that production of a small fraction of in-frame mRNA
      in muscle explains the molecular background of the intermediate type of
      dystrophinopathy in the index case. This finding underlines the potential of
      genetic therapeutic strategies aimed to modify mRNA in DMD to generate a much
      milder disease.

PMID- 12508092
TI  - Comparison of L-selectin and CD11b on neutrophils of adults and neonates during
      the first month of life.
AB  - The newborn infant is particularly susceptible to infection in the first weeks of
      life and this may be, in part, related to functional impairment of neonatal
      neutrophils in regard to adherence, chemotaxis, and migration. Differences in
      expression of the neutrophil adherence molecules, L-selectin and CD11b/CD18 (Mac
      1), have been previously demonstrated in cord blood and in very young infants
      (</= 48 h) compared with adults, but it is unknown for how long these differences
      persist. We measured surface expression of neutrophil L-selectin and CD11b using
      flow cytometry in healthy term human newborns from 24 h through 4 wk of age. We
      also measured levels of soluble L-selectin using an ELISA in neonates though the
      age of 4 wk. Compared with adults, neonates expressed significantly less L
      selectin on resting neutrophils through 4 wk of age, with the lowest levels being
      at 24 h. Expression of L-selectin on the neutrophil after activation with N
      formyl-methionyl-leucyl-phenylalanine was less in the neonate than in the adult
      (p < 0.05) for the first week of life. Soluble L-selectin showed a steady
      increase with age in the neonates. Soluble L-selectin was significantly lower in
      the 24-h neonate compared with the adult and was higher in the 4-wk neonate
      compared with the adult. CD11b expression was similar between neonates and adults
      on unstimulated neutrophils, but upon activation, the neonatal neutrophil
      demonstrated significantly lower up-regulation of CD11b on the neutrophil surface
      through 4 wk of age compared with adults (p < 0.05 for all ages except 1 wk).
      These findings that differences in expression of L-selectin and CD11b from that
      in adults persist throughout the neonatal period provide further evidence that
      these differences may play a role in the neutrophil defects observed during the
      neonatal period.

PMID- 12508093
TI  - The conserved TFLK motif of mammary-associated serum amyloid A3 is responsible
      for up-regulation of intestinal MUC3 mucin expression in vitro.
AB  - In various mammalian species, an isoform of serum amyloid A is secreted at high
      concentrations into colostrum. A conserved four-amino-acid motif (TFLK) is
      contained within the first eight N-terminal amino acid residues of this mammary
      associated serum amyloid A isoform 3 (M-SAA3). Peptides derived from the bovine N
      terminal amino acid sequence of M-SAA3 were produced and added to cell culture
      medium of HT29 cells to study the effects on intestinal mucin gene expression.
      HT29 cells were grown to enhance expression of either MUC2 or MUC3 intestinal
      mucins. After incubation, total RNA was isolated for Northern blot analyses using
      MUC2 or MUC3 mucin cDNA probes. Signals were detected by autoradiography with
      mRNA levels expressed relative to 28S rRNA. The 10-mer peptides containing the
      intact TFLK-motif or a TFLK 4-mer peptide increased MUC3 mRNA expression compared
      with control cells (p < 0.05). There was no effect of these peptides on MUC2 mRNA
      expression. Cells that were incubated with 10-mer N-terminal derived peptides
      containing a scrambled TFLK motif, with all 10 amino acid residues scrambled or
      derived from a C-terminal region of M-SAA3, did not show increased MUC3
      expression. Inhibition of enteropathogenic Escherichia coli strain E2348/69
      adhesion to HT29 cells grown to enhance MUC3 expression was reduced by a similar
      amount when either peptides containing the intact TFLK motif or probiotic
      microbes were added to cell culture medium compared with control cells. M-SAA3 is
      a bioactive peptide secreted into colostrums that can up-regulate mucin
      expression and thereby may enhance innate protective mechanisms that limit access
      of deleterious microbes to intestinal mucosal epithelial cells in the
      postparturition period.

PMID- 12508094
TI  - Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial
      cell chemokine expression in mice.
AB  - Dextran sulfate sodium (DSS) induces an inflammatory bowel disease-like colitis
      in animals. To determine the contribution of epithelium to inflammation in the
      intestine, we examined the effects of DSS in transgenic mice that specifically
      secrete macrophage inflammatory protein-2 (MIP-2) from the intestinal epithelium.
      We first confirmed the production of MIP-2 from intestinal epithelial cells by
      Western blots in transgenic mice. MIP-2 transgenic mice were therefore an
      appropriate model to examine the role of epithelial cell chemokines in an
      inflammatory state induced by DSS. We then examined the neutrophil migration into
      the intestine and the effect of DSS on this migration by myeloperoxidase
      staining. There was an increase of myeloperoxidase-positive neutrophils in the
      intestine from wild-type and transgenic mice after the DSS treatment.
      Furthermore, the increase of neutrophils under stimulation with DSS was confirmed
      quantitatively by measuring specific tissue myeloperoxidase activities. It was
      significantly greater in DSS-treated MIP-2 transgenic mice than in wild-type mice
      in both the small intestine and colon. These results suggest that the
      inflammatory effects of DSS on both small intestine and colon are enhanced by MIP
      2 secreted by epithelial cells in the transgenic mice. In conclusion, intestinal
      epithelial cells can act in concert with other inflammatory stimuli in
      maintaining inflammation.

PMID- 12508095
TI  - Adipocytokines, body composition, and fitness in children.
AB  - Recent evidence suggests a role for adipose derived cytokines (adipocytokines)
      such as tumor necrosis factor-alpha (TNF-alpha), IL-6, and the recently
      discovered adiponectin in the mechanism of impaired glucose regulation and
      atherosclerosis in adults. However, the relationship between adipocytokines and
      body composition, fasting insulin, and fitness is virtually unknown children.
      Fasting blood sampling was performed in 30 healthy, predominately Hispanic- and
      Asian-American children (16 boys, mean age 12.7 +/- 0.1 y old) from a lower
      socioeconomic area in Los Angeles. Adiposity was measured by dual x-ray
      absorptiometry (DEXA); and peak oxygen uptake using cycle ergometry. Adiponectin
      (mean 10.8 +/- 0.8 micro g/mL) was inversely correlated with body mass index
      (BMI, as percentile by age) (r = -0.48, p = 0.011) and fat mass (r = -0.43, p =
      0.03). In contrast, TNF-alpha and IL-6 were both positively correlated with BMI
      and fat mass. Adiponectin was inversely correlated with fasting insulin (r = 
      0.52, p = 0.006), but no correlations were found for insulin and either TNF-alpha
      or IL-6. Adiponectin was correlated with HDL (r = 0.448, p = 0.019).
      Paradoxically, peak oxygen consumption (an indicator of fitness) was negatively
      correlated with adiponectin levels (r = -0.471, p = 0.013) and positively
      correlated with TNF-alpha (r = 0.560, p = 0.002). In children, adipocytokines are
      correlated with fat mass, insulin sensitivity, and cardiovascular risk factors in
      a manner that is qualitatively similar to relationships recently observed in
      adults. In more obese children, the mass of fat tissue may attenuate potentially
      positive effects of fitness on circulating levels of adiponectin and TNF-alpha.
      The novel data on adiponectin suggest that deleterious dysregulation of
      adipocytokines associated with obesity may occur relatively early in life.

PMID- 12508096
TI  - Summary and abstracts of the Seventh International Kawasaki Disease Symposium:
      December 4-7, 2001, Hakone, Japan.

PMID- 12508097
TI  - History of academic general and ambulatory pediatrics.
AB  - Academic general pediatrics and ambulatory care are closely linked to the
      development of the Ambulatory Pediatric Association, an organization with nearly
      2000 members active in teaching, patient care, and research. Primary care,
      behavioral-developmental pediatrics, prevention, health promotion, community
      pediatrics, socioeconomic issues, cultural and ethnic diversity, advocacy,
      research in education, social issues, and environmental health lie within the
      purview of general pediatrics. In part, because of their teaching and patient
      care obligations, but also due to a lack of fellowship research training, many
      general pediatrics faculty have had difficulty in accomplishing significant
      research. By supporting fellowship training in general pediatrics, The Robert
      Wood Johnson Foundation General Pediatrics Academic Development Program and the
      current fellowship program supported by the Bureau of Health Manpower are
      important efforts to remedy this deficiency. The sciences basic to general
      pediatrics research include epidemiology, biostatistics, and the behavioral
      sciences. In addition, general pediatrics research often borrows from other
      sciences and collaborates with investigators in other disciplines. Partnerships
      between general pediatrics divisions and practicing pediatricians for teaching
      and research, e.g. the Community Education in Community Settings program,
      provides a realistic educational program for future pediatricians. The Pediatric
      Research in Office Setting network is another important vehicle for translation
      of research into the practice of general pediatrics. The steady growth of the
      Ambulatory Pediatric Association over the past four decades is testimony to the
      creativity, adaptability, and verve that has characterized the discipline of
      general pediatrics.

PMID- 12508099
TI  - Moderate hyperbilirubinemia is associated with an increase in minor neurologic
      dysfunction with a "strong"dose-response relationship.

PMID- 12508100
TI  - Antioxidants as therapy in the newborn: some words of caution.

PMID- 12508102
TI  - Cholera toxin internalization and intoxication.

PMID- 12508104
TI  - Cellular functions of the Rap1 GTP-binding protein: a pattern emerges.
AB  - Rap1 belongs to the Ras subgroup of small GTP-binding proteins. Whereas its early
      history has focused on its biochemical homology to Ras and the alleged functional
      antagonism between these two small GTPases, recent cellular evidence suggests
      that endogenous Rap1 plays a unique, Ras-independent role in eukaryotic cells.
      Activated by virtually all receptor types and second messengers, Rap1 controls
      adhesion-related functions such as phagocytosis, cell-cell contacts and
      functional activation of integrins through inside-out signalling. Whereas the
      precise mechanism by which its downstream effectors exert these diverse functions
      is unknown, Rap1 seems to fulfil the evolutionarily conserved function of
      patterning the eukaryotic cell, thus enabling it to respond to its environment,
      in particular through cytoskeletal remodelling.

PMID- 12508105
TI  - Sexy splicing: regulatory interplays governing sex determination from Drosophila
      to mammals.
AB  - A remarkable array of strategies is used to produce sexual differentiation in
      different species. Complex gene hierarchies govern sex determination pathways, as
      exemplified by the classic D. melanogaster paradigm, where an interplay of
      transcriptional, splicing and translational mechanisms operate. Molecular studies
      support the hypothesis that genetic sex determination pathways evolved in reverse
      order, from downstream to upstream genes, in the cascade. The recent
      identification of a role for the key regulatory factors SRY and WT1(+KTS) in pre
      mRNA splicing indicates that important steps in the mammalian sex determination
      process are likely to operate at the post-transcriptional level.

PMID- 12508106
TI  - Rescue of arrested RNA polymerase II complexes.
AB  - In the past few months, several discoveries relating to the mechanism underlying
      transcription-coupled DNA repair (TCR) have been reported. These results make it
      timely to propose a hypothesis for how eukaryotic cells might deal with arrested
      RNA polymerase II (Pol II) complexes. In this model, the transcription-repair
      coupling factor Cockayne Syndrome B (or the yeast equivalent Rad26) uses DNA
      translocase activity to remodel the Pol II-DNA interface, possibly to push the
      polymerase past the obstruction or to remove it from the DNA so that repair can
      take place if the obstacle is a DNA lesion. However, when this action is not
      possible and Pol II is left irreversibly trapped on DNA, the polymerase is
      instead ubiquitylated and eventually removed by proteolysis.

PMID- 12508107
TI  - Functional interaction of megalin with the megalinbinding protein (MegBP), a
      novel tetratrico peptide repeat-containing adaptor molecule.
AB  - Megalin is a member of the LDL receptor gene family that plays an important role
      in forebrain development and in cellular vitamin D metabolism through endocytic
      uptake of vitamin D metabolites. Similar to other receptors in this gene family,
      megalin is believed to functionally interact with intracellular proteins through
      adaptors that bind to the receptor tail and regulate its endocytic and signal
      transducing activities. Using yeast two-hybrid screens, we identified a novel
      scaffold protein with tetratrico peptide repeats, the megalin-binding protein
      (MegBP) that associates with the receptor. The binding site of MegBP was mapped
      to an N-terminal region on the receptor tail harboring a proline-rich peptide
      element. MegBP binding did not block the endocytic activity of the receptor;
      however, overexpression resulted in cellular lethality. In further screens, we
      identified proteins that bound to MegBP and thus might be recruited to the
      megalin tail. MegBP-interacting partners included several transcriptional
      regulators such as the SKI-interacting protein (SKIP), a co-activator of the
      vitamin D receptor. These finding suggest a model whereby megalin directly
      participates in transcriptional regulation through controlled sequestration or
      release of transcription factors via MegBP.

PMID- 12508108
TI  - The multi-adaptor proto-oncoprotein Cbl is a key regulator of Rac and actin
      assembly.
AB  - The induction of protein tyrosine kinase signaling pathways is a principal
      mechanism for promoting cellular activation. Biochemical and genetic analyses
      have implicated the multi-adaptor proto-oncogene protein Cbl as a key negative
      regulator of activated protein tyrosine kinases. By inhibiting the function of
      Cbl as a multi-domain adaptor protein, through expression of a truncated form
      (480-Cbl), we demonstrate that Cbl is a potent negative regulator of actin
      assembly in response to receptor tyrosine kinase (RTK) activation. Expression of
      480-Cbl dramatically enhances RTK-dependent induction of actin dorsal ruffles,
      which correlates with a pronounced increase in Rac activation. By contrast,
      mitogenic signaling by RTK targets, such as PI 3-kinase and MAP kinases, as well
      as RTK-mediated tyrosine phosphorylation do not appear to be affected by 480-Cbl
      expression. Further, we determined that Cbl undergoes a striking RTK-activation
      dependent translocation to sites of active actin dorsal ruffle nucleation. Hence,
      the selective regulation of RTK signaling to the actin cytoskeleton appears to
      result from recruitment of signaling proteins on a Cbl template bound to the
      actin cytoskeleton.

PMID- 12508109
TI  - Programmed cell death in the developing inner ear is balanced by nerve growth
      factor and insulin-like growth factor I.
AB  - Nerve growth factor induces cell death in organotypic cultures of otic vesicle
      explants. This cell death has a restricted pattern that reproduces the in vivo
      pattern of apoptosis occurring during inner ear development. In this study, we
      show that binding of nerve growth factor to its low affinity p75 neurotrophin
      receptor is essential to achieve the apoptotic response. Blockage of binding to
      p75 receptor neutralized nerve-growth-factor-induced cell death, as measured by
      immunoassays detecting the presence of cytosolic oligonucleosomes and by TUNEL
      assay to visualize DNA fragmentation. Nerve growth factor also induced a number
      of cell-death-related intracellular events including ceramide generation, caspase
      activation and poly-(ADP ribose) polymerase cleavage. Again, p75 receptor
      blockade completely abolished all of these effects. Concerning the intracellular
      pathway, ceramide increase depended on initiator caspases, whereas its actions
      depended on both initiator and effector caspases, as shown by using site-specific
      caspase inhibitors. Conversely, insulin-like growth factor I, which promotes cell
      growth and survival in the inner ear, abolished apoptosis induced by nerve growth
      factor. Insulin-like growth factor cytoprotective actions were accomplished, at
      least in part, by decreasing endogenous ceramide levels and activating Akt. Taken
      together, these results strongly suggest that regulation of nerve-growth-factor
      induced apoptosis in the otocysts occurs via p75 receptor binding and is strictly
      controlled by the interaction with survival signalling pathways.

PMID- 12508110
TI  - A plant cyclin B2 is degraded early in mitosis and its ectopic expression
      shortens G2-phase and alleviates the DNA-damage checkpoint.
AB  - Mitotic progression is timely regulated by the accumulation and degradation of A-
      and B-type cyclins. In plants, there are three classes of A-, and two classes of
      B-type cyclins, but their specific roles are not known. We have generated
      transgenic tobacco plants in which the ectopic expression of a plant cyclin B2
      gene is under the control of a tetracycline-inducible promoter. We show that the
      induction of cyclin B2 expression in cultured cells during G2 phase accelerates
      the entry into mitosis and allows cells to override the replication checkpoint
      induced by hydroxyurea in the simultaneous presence of caffeine or okadaic acid,
      drugs that are known to alleviate checkpoint control. These results indicate that
      in plants, a B2-type cyclin is a rate-limiting regulator for the entry into
      mitosis and a cyclin B2-CDK complex might be a target for checkpoint control
      pathways. The cyclin B2 localization and the timing of its degradation during
      mitosis corroborate these conclusions: cyclin B2 protein is confined to the
      nucleus and during mitosis it is only present during a short time window until
      mid prophase, but it is effectively degraded from this timepoint onwards.
      Although cyclin B2 is not present in cells arrested by the spindle checkpoint in
      metaphase, cyclin B1 is accumulating in these cells. Ectopic expression of cyclin
      B2 in developing plants interferes with differentiation events and specifically
      blocks root regeneration, indicating the importance of control mechanisms at the
      G2- to M-phase transition during plant developmental processes.

PMID- 12508111
TI  - The transcription factor Slug represses E-cadherin expression and induces
      epithelial to mesenchymal transitions: a comparison with Snail and E47
      repressors.
AB  - Transcriptional repression mechanisms have emerged as one of the crucial
      processes for the downregulation of E-cadherin expression during development and
      tumour progression. Recently, several E-cadherin transcriptional repressors have
      been characterized (Snail, E12/E47, ZEB-1 and SIP-1) and shown to act through an
      interaction with proximal E-boxes of the E-cadherin promoter. We have analyzed
      the participation of another member of the Snail family, Slug, and observed that
      it also behaves as a repressor of E-cadherin expression. Stable expression of
      Slug in MDCK cells leads to the full repression of E-cadherin at transcriptional
      level and triggers a complete epithelial to mesenchymal transition. Slug-induced
      repression of E-cadherin is mediated by its binding to proximal E-boxes,
      particularly to the E-pal element of the mouse promoter. Detailed analysis of the
      binding affinity of different repressors to the E-pal element indicates that Slug
      binds with lower affinity than Snail and E47 proteins. These results, together
      with the known expression patterns of these factors in embryonic development and
      carcinoma cell lines, support the idea that the in vivo action of the different
      factors in E-cadherin repression can be modulated by their relative
      concentrations as well as by specific cellular or tumour contexts.

PMID- 12508112
TI  - Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by
      independent mechanisms that modify the induction of heat-shock proteins 70 and 25
      differently.
AB  - Nuclear domains called ND10 or PML bodies might function as nuclear depots by
      recruiting or releasing certain proteins. Although recruitment of proteins
      through interferon-induced upregulation and SUMO-1 modification level of PML had
      been defined, it is not known whether release of proteins is regulated and has
      physiological consequences. Exposure to sublethal environmental stress revealed a
      sequential release of ND10-associated proteins. Upon heat shock Daxx and Sp100
      were released but PML remained, whereas exposure to subtoxic concentrations of
      CdCl(2) induced the release of ND10-associated proteins, including PML, with
      Sp100 remaining in a few sites. In both cases, recovery times were similar and
      were followed by a burst of mitotic activity. Cadmium-induced release of proteins
      from ND10 could be blocked by inhibiting activation of p38 MAPK or ERK1/2. By
      contrast, heat-shock-induced desumolation of PML and release of proteins from
      ND10 are unaffected by these inhibitors but can be recapitulated by
      overexpression of the SUMO isopeptidase SENP-1. Therefore, activation of SENP-1
      like SUMO isopeptidase(s) during heat shock is not affected by these kinases.
      Thus, the release of ND10-associated proteins is not due to a general dispersal
      of nuclear domains but seems to be regulated by rapid desumolation during thermal
      stress and through the phosphorylation cascade of stress and mitogenic signaling
      pathways in the case of CdCl(2). Whether the release of certain proteins had
      consequences was tested for heat-shock-protein transcription and synthesis.
      Release of Daxx correlated with Hsp25 suppression, suggesting that Daxx normally
      inhibits immediate Hsp25 production. Release of PML correlated with lower
      production of Hsp70. These results suggest that segregation or release of PML or
      Daxx have differential physiological relevance during the stress response. The
      fact that enzymatic activation of protein release or segregation after stress
      modifies the heat-shock response strengthens the concept of ND10 as a regulated
      depot of effector proteins.

PMID- 12508113
TI  - Outer mitochondrial membrane permeabilization during apoptosis triggers caspase
      independent mitochondrial and caspase-dependent plasma membrane potential
      depolarization: a single-cell analysis.
AB  - Little is known about the temporal relationship between mitochondrial and plasma
      membrane potential changes and outer mitochondrial membrane permeabilization
      during apoptosis. Confocal imaging of breast carcinoma and HeLa cells stably
      transfected with cytochrome-C-GFP demonstrated that mitochondria rapidly
      depolarized after the release of the fusion protein into the cytosol. Of note,
      mitochondria did not completely depolarize but established a new steady-state
      level that could be further dissipated by treatment with the protonophore
      carbonyl cyanide p-trifluoromethoxy-phenylhydrazone. Treatment with the F(O)F(1)
      ATP-synthase inhibitor oligomycin likewise induced a collapse of this steady
      state level, suggesting that F(O)F(1)-ATP-synthase reversal maintained
      mitochondrial potential after outer mitochondrial membrane permeabilization.
      Treatment with a broad spectrum caspase inhibitor failed to inhibit the partial
      depolarization of mitochondria during apoptosis, yet potently abolished the
      activation of effector caspases detected by fluorescence resonance energy
      transfer analysis in the same experiment. Interestingly, the onset of
      mitochondrial depolarization was always coupled with a depolarization of the
      plasma membrane potential. This was associated with the degradation of the
      regulatory Na(+)/K(+)-ATPase beta-subunit, and both events were blocked by
      caspase inhibition. Our results demonstrate that outer mitochondrial membrane
      permeabilization coordinates the depolarization of both membrane potentials
      during apoptosis.

PMID- 12508114
TI  - Phosphorylation of FcgammaRIIA is required for the receptor-induced actin
      rearrangement and capping: the role of membrane rafts.
AB  - Activation of Fcgamma receptor II (FcgammaRII) induces rearrangement of the actin
      based cytoskeleton that serves as a driving force for FcgammaRII-mediated
      phagocytosis and FcgammaRII capping. To get insight into the signaling events
      that lead to the actin reorganization we investigated the role of raft-associated
      Src family tyrosine kinases in capping of FcgammaRII in U937 cells. After
      crosslinking, FcgammaRII was found to be recruited to detergent-resistant
      membrane domains (DRMs), rafts, where it coexisted with Lyn kinase and underwent
      tyrosine phosphorylation. Lyn was displaced from DRMs under the influence of DL
      alpha-hydroxymyristic acid and 2-bromopalmitic acid, agents blocking N-terminal
      myristoylation and palmitoylation of proteins, respectively, and after disruption
      of DRM integrity by depletion of plasma membrane cholesterol with beta
      cyclodextrin. Under these conditions, phosphorylation of the crosslinked
      FcgammaRII was diminished and assembly of FcgammaRII caps was blocked. The
      similar reduction of FcgammaRII cap formation correlated with inhibition of
      receptor phosphorylation was achieved with the use of PP1 and herbimycin A,
      specific inhibitors of Src family tyrosine kinases. Phosphorylation of
      FcgammaRIIA expressed in BHK cells, lacking endogenous FcgammaRs, was abolished
      by substitution of tyrosine 298 by phenylalanine in the ITAM of the receptor. The
      mutant receptor did not undergo translocation towards cap-like structures and
      failed to promote the receptor-mediated spreading of the cells, as compared to
      BHK cells transfected with the wild-type FcgammaRIIA. On the basis of these data,
      we suggest that tyrosine phosphorylation of activated FcgammaRIIA by raft
      residing tyrosine kinases of the Src family triggers signaling pathways that
      control the rearrangement of the actin cytoskeleton required for FcgammaRII
      mediated motility.

PMID- 12508115
TI  - The pairing of X and Y chromosomes during meiotic prophase in the marsupial
      species Thylamys elegans is maintained by a dense plate developed from their
      axial elements.
AB  - Unlike eutherian males, pairing of the sex chromosomes in marsupial males during
      the first meiotic prophase is not mediated by a synaptonemal complex. Instead, a
      specific structure, the dense plate, develops during pachytene between the sex
      chromosomes. We have investigated the development and structural nature of this
      asynaptic association in males of the marsupial species Thylamys elegans by means
      of immunolabelling and electron microscopy techniques. Our results show that the
      behaviour of male marsupial sex chromosomes during first meiotic prophase is
      complex, involving modifications of their structure and/or composition. Pairing
      of the sex chromosomes and formation of the dense plate take place in mid
      pachytene, paralleling morphological changes in the sex chromosomal axial
      elements. Components of the central element of the synaptonemal complex were not
      found in the sex body, in agreement with ultrastructural studies that reported
      the absence of a canonical tripartite synaptonemal complex between male marsupial
      sex chromosomes. Interestingly, the dense plate is labelled with antibodies
      against the SCP3 protein of the lateral elements of the synaptonemal complex.
      Moreover, as sex chromosome axial elements decrease in mass throughout mid-late
      pachytene, the dense plate increases, suggesting that material moves from the
      axial elements to the dense plate. Additionally, both sex chromosome axial
      elements and the dense plate have proteins that are specifically phosphorylated,
      as revealed by their labelling with the MPM-2 antibody, indicating that they
      undergo a chromosome-specific regulation process throughout first meiotic
      prophase. We propose that the unique modifications of the composition and
      structure of the axial elements of the sex chromosomes in meiotic prophase may
      result in the prescription of synaptonemal complex formation between male
      marsupial sex chromosomes, where the dense plate is an extension of the axial
      elements of sex chromosomes. This replaces synapsis to maintain X and Y
      association during first meiotic prophase.

PMID- 12508116
TI  - Nuclear oscillations and nuclear filament formation accompany single-strand
      annealing repair of a dicentric chromosome in Saccharomyces cerevisiae.
AB  - Dicentric chromosomes undergo breakage during mitosis as a result of the
      attachment of two centromeres on one sister chromatid to opposite spindle poles.
      Studies utilizing a conditional dicentric chromosome III in Saccharomyces
      cerevisiae have shown that dicentric chromosome repair occurs primarily by
      deletion of one centromere via a RAD52-dependent recombination pathway. We report
      that dicentric chromosome resolution requires RAD1, a gene involved in the single
      strand annealing DNA repair pathway. We additionally show that single-strand
      annealing repair of a dicentric chromosome can occur in the absence of RAD52.
      RAD52-independent repair requires the adaptation-defective cdc5-ad allele of the
      yeast polo kinase and the DNA damage checkpoint gene RAD9. Dicentric chromosome
      breakage in cdc5-ad rad52 mutant cells is associated with a prolonged mitotic
      arrest, during which nuclei undergo microtubule-dependent oscillations,
      accompanied by dynamic changes in nuclear morphology. We further demonstrate that
      the frequency of spontaneous direct repeat recombination is suppressed in yeast
      cells treated with benomyl, a drug that perturbs microtubules. Our findings
      indicate that microtubule-dependent processes facilitate recombination.

PMID- 12508117
TI  - NuMA and nuclear lamins behave differently in Fas-mediated apoptosis.
AB  - NuMA is a nuclear matrix protein that has an essential function in the
      organization of the mitotic spindle. Here we have studied the fate of NuMA in Fas
      treated apoptotic Jurkat T and HeLa cells. We show that in both cell lines NuMA
      is an early target protein for caspases and that NuMA is cleaved coincidently
      with poly(ADP-ribose) polymerase-1 (PARP-1) and nuclear lamin B. NuMA is cleaved
      differently in Jurkat T and HeLa cells, suggesting that different sets of
      caspases are activated in these cell lines. The normal diffuse intranuclear
      distribution of NuMA changed during apoptosis: first NuMA condensed, then
      concentrated in the center of the nucleus and finally encircled the nuclear
      fragments within the apoptotic bodies. NuMA seems to be preferentially cleaved by
      caspase-3 in vivo since it was not cleaved in staurosporine-treated caspase-3
      null MCF-7 breast cancer cells. The cleavage of NuMA, lamin B and PARP-1 was
      inhibited in the presence of three different caspase inhibitors: z-DEVD-FMK, z
      VEID-FMK and z-IETD-FMK. Furthermore, in the presence of caspase inhibitors
      approximately 5-10% of the cells showed atypical apoptotic morphology. These
      cells had convoluted nuclei, altered chromatin structure and additionally, they
      were negative for NuMA and lamins. Since caspase-8, -3 and -7 were not activated
      and PARP was not cleaved in these cells as judged by western blotting and
      immunofluorescence studies, it is likely that this is an atypical form of
      programmed cell death owing to a proteinase(s) independent of caspases. These
      results characterize the role of NuMA in programmed cell death and suggest that
      cleavage of NuMA plays a role in apoptotic nuclear breakdown.

PMID- 12508118
TI  - A zebrafish homologue of the chemokine receptor Cxcr4 is a germ-cell guidance
      receptor.
AB  - Germ cells preserve an individual's genetic information and transmit it to the
      next generation. Early in development germ cells are set aside and undergo a
      specialized developmental programme, a hallmark of which is the migration from
      their site of origin to the future gonad. In Drosophila, several factors have
      been identified that control germ-cell migration to their target tissues;
      however, the germ-cell chemoattractant or its receptor have remained unknown.
      Here we apply genetics and in vivo imaging to show that odysseus, a zebrafish
      homologue of the G-protein-coupled chemokine receptor Cxcr4, is required
      specifically in germ cells for their chemotaxis. odysseus mutant germ cells are
      able to activate the migratory programme, but fail to undergo directed migration
      towards their target tissue, resulting in randomly dispersed germ cells. SDF-1,
      the presumptive cognate ligand for Cxcr4, shows a similar loss-of-function
      phenotype and can recruit germ cells to ectopic sites in the embryo, thus
      identifying a vertebrate ligand-receptor pair guiding migratory germ cells at all
      stages of migration towards their target.

PMID- 12508119
TI  - Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of
      inflammation.
AB  - Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity
      and mortality in diverse human diseases including endotoxaemia, sepsis,
      rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous
      mechanisms normally regulate the magnitude of innate immune responses and prevent
      excessive inflammation. The nervous system, through the vagus nerve, can inhibit
      significantly and rapidly the release of macrophage TNF, and attenuate systemic
      inflammatory responses. This physiological mechanism, termed the 'cholinergic
      anti-inflammatory pathway' has major implications in immunology and in
      therapeutics; however, the identity of the essential macrophage acetylcholine
      mediated (cholinergic) receptor that responds to vagus nerve signals was
      previously unknown. Here we report that the nicotinic acetylcholine receptor
      alpha7 subunit is required for acetylcholine inhibition of macrophage TNF
      release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild
      type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the
      nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting
      cytokine synthesis by the cholinergic anti-inflammatory pathway.

PMID- 12508120
TI  - Modelling vaccination strategies against foot-and-mouth disease.
AB  - Vaccination has proved a powerful defence against a range of infectious diseases
      of humans and animals. However, its potential to control major epidemics of foot
      and-mouth disease (FMD) in livestock is contentious. Using an individual farm
      based model, we consider either national prophylactic vaccination campaigns in
      advance of an outbreak, or combinations of reactive vaccination and culling
      strategies during an epidemic. Consistent with standard epidemiological theory,
      mass prophylactic vaccination could reduce greatly the potential for a major
      epidemic, while the targeting of high-risk farms increases efficiency. Given
      sufficient resources and preparation, a combination of reactive vaccination and
      culling might control ongoing epidemics. We also explore a reactive strategy,
      'predictive' vaccination, which targets key spatial transmission loci and can
      reduce markedly the long tail that characterizes many FMD epidemics. These
      analyses have broader implications for the control of human and livestock
      infectious diseases in heterogeneous spatial landscapes.

PMID- 12508122
TI  - CD 99 and CD 106 (VCAM-1) in human testis.
AB  - AIM: The expression of the cytokines IL-2, IL-6, IL-10, IFN-g and TNF-a and the
      adhesion proteins CD99 and CD106 was studied in the human testis at the protein
      level. METHODS: The expression of the cytokines and the adhesion proteins was
      assessed using immunohistochemistry and immunoblotting. RESULTS: None of the
      cytokines studied was present in the human testis, but CD99 and CD106 (VCAM-1)
      strongly were expressed in all the testes investigated. CD99 was present in the
      interstitial tissue of the human testis as well as in the Sertoli cells. The
      identity of the CD99+ interstitial cells is unclear. CD106 (VCAM-1) was present
      in Leydig cells as well as the basal parts of the Sertoli cells in the
      seminiferous tubules. In immunoblotting, CD99 was demonstrated at molecular
      ratios of 46-57 (kD). This is a novel isoform of the molecule. CONCLUSION: The
      human testis produces both CD99 and CD106 and as CD106 mediates cell binding to
      lymphocytes, it is possible that the human Leydig cells adhere to lymphocytes
      like the rodent Leydig cells.

PMID- 12508121
TI  - The DNA sequence and analysis of human chromosome 14.
AB  - Chromosome 14 is one of five acrocentric chromosomes in the human genome. These
      chromosomes are characterized by a heterochromatic short arm that contains
      essentially ribosomal RNA genes, and a euchromatic long arm in which most, if not
      all, of the protein-coding genes are located. The finished sequence of human
      chromosome 14 comprises 87,410,661 base pairs, representing 100% of its
      euchromatic portion, in a single continuous segment covering the entire long arm
      with no gaps. Two loci of crucial importance for the immune system, as well as
      more than 60 disease genes, have been localized so far on chromosome 14. We
      identified 1,050 genes and gene fragments, and 393 pseudogenes. On the basis of
      comparisons with other vertebrate genomes, we estimate that more than 96% of the
      chromosome 14 genes have been annotated. From an analysis of the CpG island
      occurrences, we estimate that 70% of these annotated genes are complete at their
      5' end.

PMID- 12508123
TI  - Effects of extra-corporeal shock waves on penile hemodynamics and histopathology
      in rats.
AB  - AIM: To study the effect of extra-corporeal shock wave (ESW) on the penile
      hemodynamics and histopathology in rats. METHODS: Adult male Sprague-Dawley rats
      were divided at random into 3 groups. ESW application was performed with a
      Siemens Lithostar with the rats under anesthesia lying prone on the balloon
      probe. Rats in Group I received a total of 1000 shocks at 18 kV and immediately
      underwent hemodynamic evaluation performed by direct electrostimulation of the
      cavernous nerve and measurement of intracavernous pressure (ICP). Rats in Group
      II received 3 times 1000 shocks at 18 kV at weekly intervals and hemodynamic
      evaluation was performed 1 month after the last ESW application. Group III served
      as the control. Histopathological examinations of penile tissues were done on
      Masson's trichrome and hematoxylin and eosin stained sections. RESULTS: Penile
      hemodynamic evaluation showed a trend toward a diminished mean maximal ICP,
      duration of erection, ICP during the plateau phase and maximal ICP/ blood
      pressure ratio in Group I, although there was no significant significance. The
      mean latency period in Groups I and II was prolonged. Petechial bleeding within
      tunical layers and small foci of hemorrhage within the corpora cavernosa were
      observed in Group I. However, histopathological examination failed to reveal any
      significant differences between the groups in terms of smooth muscle content,
      tunical thickness, organization of collagen bundles and elastic fiber-lattice
      framework. CONCLUSION: ESW has certain damaging effects on the penis.

PMID- 12508124
TI  - Clinical significance of EGF and EGFR expression changes in cryptorchid boys.
AB  - AIM: To explore the changes of epidermal growth factor (EGF) and epidermal growth
      factor receptor (EGFR) expressions in cryptorchid children and their clinical
      significance. METHODS: The level of serum EGF was measured by radioimmunoassay
      (RIA) and the expression of EGFR by immunohistochemistry. RESULTS: (1) The level
      of serum EGF was significantly lower in cryptorchid children than in normal
      subjects at age group of 5-9 years (P<0.01) and 10-14 years (P<0.01), (2) The
      level of EGF was significantly lower in boys with impalpable testis than in those
      with extracanalicular and intracanalicular testes (P<0.01), (3) The serum EGF
      level increased significantly 6 months after orchiopexy (P<0.05), (4) The EGFR
      expression in testicular Leydig's cells was lower in 2 approximately 4 year-old
      boys than in those over 5 years (P<0.05) and (5) the EGFR expression was less
      positive in the impalpable group and the intracanalicular group than that of the
      extracanalicular group (P<0.01). CONCLUSION: The EGF and EGFR expressions may
      correlate with the age and the position of testes; orchiopexy improves the EGF
      and EGFR expressions in cryptorchid boys.

PMID- 12508125
TI  - AZF microdeletions associated with idiopathic and non-idiopathic cases with
      cryptorchidism and varicocele.
AB  - AIM: To identify submicroscopic interstitial deletions in azoospermia factor
      (AZF) loci in idiopathic and non-idiopathic cases of male infertility in Indians.
      METHODS: One hundred and twenty two infertile males with oligozoospermia or
      azoospermia were included in this study. Semen analysis was done to determine the
      sperm density, i.e., normospermia (>20 million/mL), oligozoospermia (<20
      million/mL) or azoospermia. They were subjected to detailed clinical examination
      and endocrinological and cytogenetic study. Thirty G-banded metaphases were
      analyzed in the 122 cases and polymerase chain reaction (PCR) microdeletion
      analysis was done in 70 cytogenetically normal subjects. For this genomic DNA was
      extracted using peripheral blood. The STS primers tested in each case were sY84,
      sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). PCR amplifications found
      to be negative were repeated at least 3 times to confirm the deletion of a given
      marker. The PCR products were analyzed on a 1.8 % agarose gel. RESULTS: Eight of
      the 70 cases (11.4 %) showed deletion of at least one of the STS markers.
      Deletions were detected in cases with known and unknown aetiology with bilateral
      severe testiculopathy and also in cryptorchid and varicocele subjects.
      CONCLUSION: AZF microdeletions were seen in both idiopathic and non-idiopathic
      cases with cryptorchidism and varicocele. The finding of a genetic aetiology in
      infertile men with varicocele and cryptorchidism suggests the need for molecular
      screening in non-idiopathic cases.

PMID- 12508126
TI  - PCR analysis of Yq microdeletions in infertile males, a study from South India.
AB  - AIM: To estimate the frequency of microdeletions in the long arm of Y-chromosome
      of 20 infertile males from South India. METHODS: Polymerase chain reaction (PCR)
      amplification using Y-specific STS of azoospermia factor (AZF) regions i.e., SY
      84 for AZFa, SY 127 for AZFb and SY 254 for AZFc. RESULTS: Of the 20 infertile
      subjects 3 (15 %), one azoospermic and two oligozoospermic, showed microdeletions
      in the AZF region of Y-chromosome. CONCLUSION: The frequency of deletions
      involving AZF region of the Y-chromosome is 15 % in azoospermic and severely
      oligozoospermic infertile men. PCR amplification of AZF locus is useful for the
      diagnosis of microdeletions in the Y-chromosome.

PMID- 12508127
TI  - Characteristic pattern of human prostatic growth with age.
AB  - AIM: To study the characteristic pattern of the age-related growth of the human
      prostate gland. METHODS: The volume (weight) of the prostate in 1,601 males, aged
      from newborn to 92 years, was determined by B-ultrasonography. RESULTS: Prostatic
      volume determination by B-ultrasonography in 1601 males (1301 normal subjects and
      300 BPH patients) pointed out that the age-stratified growth of human prostate
      could be categorized into 4 life stages: (1) the first slow growing phase (from
      newborn to 9 years): the prostate grows slowly at a rate of 0.14 g per year; (2)
      the first rapid growing phase (from 10 to 30 years): the prostate grows at a rate
      of 0.84 g per year; (3) the second slow growing phase (from 30 to 50 years), the
      prostate grows at a rate of 0.21 g per year; (4) the second rapid growing phase
      (from 50 to 90 years): the prostate grows at one of the following rates: in one
      group the growth rate is of 0.50 g per year and in the other 1.20 g per year,
      leading to benign prostatic hyperplasia (BPH). CONCLUSION: The volumes of the
      prostate are different in different age groups and it grows with age at different
      rates in four life phases. The prostate growth in phases can be expressed by the
      following equation: Y=19.36+1.36X'-0.58X'(2+0.33X'3), where Y = prostate volume,
      X = age (up to 70 years), X'=(X-35.5)/10.

PMID- 12508128
TI  - Effect of adrenalectomy on rat epididymidis.
AB  - AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of
      Sprague-Dawley rats. METHODS: The histological, biochemical (cholesterol protein,
      zinc, copper, alkaline and acid phosphatase aryl sulphatase, lactic dehydrogenase
      and leucine amino peptidase) and hormonal (FSH, LH and testosterone) changes of
      caput and cauda epididymis in ADX rats were observed. RESULTS: Organ wet weight,
      histological studies and morphometric measurements indicated a cellular
      degeneration in caput and cauda epididymis of ADX rats. Serum testosterone level
      was significantly lower in ADX than in sham-operated rats, while the serum FSH
      and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was
      higher in ADX than in sham-operated rats. Epididymal zinc level increased whereas
      copper level decreased in ADX rats compared to the sham-operated. CONCLUSION:
      Adrenalectomy leads to degeneration of caput and cauda epididymidis epithelial
      cells as a result of decreased supply of testosterone.

PMID- 12508129
TI  - Evaluation and assessment of semen for IVF/ICSI.
AB  - Evaluation and assessment of semen is very important for both diagnosis of male
      infertility and selection of patients for treatment with IVF or ICSI. In standard
      IVF, sperm function is essential for normal fertilization: sperm must be able to
      bind to zona pellucida (ZP), undergo the acrosome reaction and penetrate the ZP
      and fuse with the oolemma before fertilization takes place. In contrast, most
      sperm functions are not required for fertilization in ICSI since sperm bypass the
      ZP and oolemma by injection of a single sperm directly into cytoplasm of oocyte.
      Therefore, the clinical decision on treatment of patients with either IVF or ICSI
      is mostly dependent on results of sperm tests. However, conventional semen
      analyses do not provide accurate information about sperm fertilizing ability
      since many patients with subtle sperm defects can not be detected. More advanced
      sperm function tests are required to detect sperm defects that may lead to
      failure of fertilization in standard IVF. In the last 15 years we performed
      extensive studies on relationship between sperm functions and fertilization rates
      by logistic regression analysis in large numbers of IVF patients including 370
      patients with zero fertilization rate by IVF. We confirmed sperm morphology
      assessed strictly was strongly related to fertilisation rate with standard IVF.
      Thus sperm morphology assessment is very useful for selection of patients for
      ICSI. We also developed a number of new tests including sperm-ZP binding, sperm
      ZP penetration and the ZP-induced AR and evaluated the clinical value of these
      tests. Sperm-ZP binding and sperm-ZP penetration tests are the most powerful
      indicators for sperm fertilizing ability in vitro. The ZP-induced AR is highly
      correlated with sperm-ZP penetration. We discovered a condition we call
      disordered ZP-induced AR which causes serve infertility in up to 25% men with
      otherwise idiopathic infertility In conclusion, the combination of semen analysis
      with advanced sperm function tests provide important diagnostic and prognostic
      information for male infertility and is crucial for selection of patients for
      treatment with IVF or ICSI.

PMID- 12508130
TI  - Roles of dopaminergic receptors in bladder and erectile function at the spinal
      level.

PMID- 12508131
TI  - Effect of fexofenadine, a mast cell blocker, in infertile men with significantly
      increased testicular mast cells.
AB  - AIM: To investigate the role of fexofenadine, a mast cell blocker, on semen
      quality in the treatment of infertile men. METHODS: The study included 16 Turkish
      idiopathic infertile men with azoospermia or oligozoospermia who underwent
      testicular biopsy to examine mast cells containing tryptase. In all patients, a
      complete medical history, clinical examination, semen analysis and serum hormone
      assay were carried out. The biopsy specimens were immunohistochemically stained
      with antihuman tryptase for mast cells. The number of total mast cells per
      seminiferous tubule was calculated and recorded as mast cell index. The patients
      were divided into two groups according to their mast cell index: the higher (> or
      =1, n=9) and the lower (<1, n=7) index groups. Fexofenadine was administered
      orally at a dose of 180 mg/day for 4 to 9 months. Pre- and post-treatment semen
      parameters, including total motile sperm counts (TMC) were recorded and compared.
      Spontaneous pregnancies after the treatment were registered. RESULTS: There was
      no statistically significant difference in TMC between the pre-treatment and post
      treatment values in patients with higher and lower mast cell index (P> or =0.05).
      In both groups, nobody had a significant response to the treatment and there was
      no spontaneous pregnancy after the treatment. CONCLUSION: Although testicular
      dysfunction is closely associated with increased number of testicular mast cells,
      fexofenadine, a mast cell blocker, appears not having any benefit in the
      treatment of Turkish infertile men with a significant increase in testicular mast
      cells.

PMID- 12508132
TI  - Effect of Withania somnifera root extract on the sexual behaviour of male rats.
AB  - AIM: To determine the effect of a methanolic extract of Withania somnifera (L.)
      Dunal roots on sexual competence of male rats. METHODS: Male rats were orally
      administered 3000 mg.kg-1.day-1 of root extract for 7 days. Their sexual
      behaviour was evaluated 7 days prior to treatment, day 3 and 7 of treatment, and
      day 7, 14 and 30 post-treatment by pairing each male with a receptive female.
      RESULTS: The root extract induced a marked impairment in libido, sexual
      performance, sexual vigour, and penile erectile dysfunction. These effects were
      partly reversible on cessation of treatment. These antimasculine effects are not
      due to changes in testosterone levels or toxicity but may be attributed to
      hyperprolactinemic, GABAergic, serotonergic or sedative activities of the
      extract. CONCLUSION: Use of W. somnifera roots may be detrimental to male sexual
      competence.

PMID- 12508133
TI  - Evaluation of androgenic activity of Zingiber officinale and Pentadiplandra
      brazzeana in male rats.
AB  - AIM: Aqueous extracts of Zingiber officinale and Pentadiplandra brazzeana were
      tested for their possible androgenic activity in male Wistar rats. METHODS: The
      aqueous extracts of the two plants were gavaged separately to 2 groups of rats at
      a similar dose of 600 mg middot kg(-1) middot day(-1) for 8 days. At the end of
      the treatment, the animals were killed and the blood, testis, epididymis, seminal
      vesicles and prostate were collected for biochemical analysis. RESULTS: The
      aqueous extract of Z. officinale significantly increased in the relative weight
      of the testis, the serum testosterone level, testicular cholesterol level and
      epididymal a-glucosidase activity. The aqueous extract of P. brazzeana
      significantly increased the weights of the testis, seminal vesicles and prostate.
      It also significantly increased the serum and testicular testosterone level. The
      fructose, alpha-glucosidase and cholesterol levels in P. brazzeana-treated rats
      were increased by 28 %, 35 % and 114 %, respectively. CONCLUSION: The aqueous
      extracts of both P. brazzeana and Z. officinale have an androgenic activity,
      which seems to be more potent with P. brazzeana than with Z. officinale.

PMID- 12508134
TI  - Extracorporeal shock-wave versus pneumatic ureteroscopic lithotripsy in treatment
      of lower ureteral calculi.
AB  - AIM: To compare the efficacy and complications of extracorporeal shock-wave
      lithotripsy (SWL) and pneumatic ureteroscopic lithotripsy (URS) in the treatment
      of lower ureteral calculi. METHODS: From August 1997 to June 1999, 210 patients
      with calculi in the distal third of the ureter were treated with SWL and the
      other 180 with URS. The stones were fragmented with either HB-ESWL-V lithotripter
      or JML-93 pneumatic lithotripter through Wolf 7.5 approximately 9.0 Fr
      ureteroscope. The outcome was assessed in terms of stone clearance rate, re
      treatment rate and complication incidence. RESULTS: The stone clearance rate was
      78.1 % with SWL and 93.3 % with URS (P<0.05). SWL had a re-treatment rate of 11.9
      %, vs 2.2 % in the URS group (P<0.05). URS caused ureteral perforation in 3.3% of
      patients, while it was 0 with SWL (P<0.05). The differences in the incidence of
      other complications such as infection and stricture between the two groups were
      insignificant. CONCLUSION: Though the selection of these two options depends on
      equipments available and the expertise of the operator, we recommend URS as the
      optimal treatment for distal ureteral calculi.

PMID- 12508135
TI  - Oligospermia due to partial maturation arrest responds to low dose estrogen
      testosterone combination therapy resulting in live-birth: a case report.
AB  - A man having severe oligospermia, due to partial maturation arrest at spermatid
      stage, was given low dose estrogen-testosterone combination therapy for three
      months. His sperm count increased enormously, following which his wife conceived
      and delivered a healthy baby at term.

PMID- 12508136
TI  - Effect of mercuric chloride on membrane-bound enzymes in rat testis.
AB  - AIM: To study the effect of mercuric chloride on the membrane-bound enzymes.
      METHODS: The effect of mercuric chloride at two different doses, 1 mg/kg (low
      dose) and 2 mg/kg (high dose), orally for 30 days, was observed on the membrane
      bound enzymes in the testis of adult albino rats. RESULTS: Mercuric chloride
      significantly decreased the body weight and testis weight in the high dose group
      (P< 0.05), but not in the low dose group. The activities of 5'nucleotidase and
      adenosine triphosphatases were markedly decreased (P< 0.01) in the testis of both
      groups. Alkaline phosphatase and ggr-glutamyl transferase activities were
      significantly increased (P< 0.01) in both groups. However, the effect was more
      pronounced in the high than in the low dose groups. CONCLUSION: The dose
      dependent effect of mercuric chloride on these enzymes may affect the membrane
      characteristics and thereby the fertility of the animal.

PMID- 12508137
TI  - Open regulation and practice in assisted dying.
AB  - The Netherlands, Oregon and Switzerland are the only areas in the world where
      assistance in dying has legally been practised in recent years. This article
      provides a detailed comparison of the history of the origins, legislation,
      monitoring systems and the extent of assistance in dying in these three places.
      It shows that the actual practice in Switzerland which, unlike Oregon, also
      allows assistance in suicide by means of infusions or gastric tubes, can today be
      technically quite similar to the permitted practice of active euthanasia on
      request in the Netherlands. Considering the preconditions restricting these
      practices, Swiss regulations are the most open, in that the law requires neither
      a medical second opinion (as in both the Netherlands and Oregon) nor the
      existence of a terminal illness (as in Oregon) as prerequisite to assistance in
      dying. In 2001, the proportion of assisted deaths (as reported to the
      authorities) in all deaths was almost ten times higher in the Netherlands (1.5%
      of all deaths) then in Oregon (<0.1% of all deaths) or Switzerland (0.2% of all
      deaths). The analysis of the different normative concepts underlying legislation
      reveals that in the Netherlands the basis for non-prosecution lies in the
      conflict of the physician's duties to respect life versus relief of suffering,
      while in the USA and in Switzerland the right-to-die concept plays a major role.
      These two concepts allow appreciation of distinctions between the roles of the
      physician in end-of-life practices and between assisted suicide and voluntary
      active euthanasia.

PMID- 12508138
TI  - Feasibility of the new WHO classification of pulmonary neuroendocrine tumours.
AB  - Primary pulmonary neuroendocrine tumours present a heterogeneous group of tumours
      causing problems in diagnosis and treatment. The new WHO classification of lung
      tumours was published in 1999 in order to improve this situation by combining
      morphology, immunohistochemistry and clinical background for diagnosis. The aim
      of our study was to evaluate the feasibility of this classification and to
      discuss the consequences of modified diagnostic criteria. 50 cases of
      neuroendocrine tumours and 50 poorly differentiated lung tumours diagnosed in the
      years 1981-1994 were independently evaluated by three pathologists. The diagnosis
      of all 27 typical carcinoids (TC) was given by all authors, however, no unanimous
      agreement was achieved in one of three atypical carcinoids (AC) and two of four
      large cell neuroendocrine carcinomas (LCNEC). While typical and atypical
      carcinoids can be distinguished by the number of mitoses or presence of necrosis
      it was found that the most difficult diagnostic factor for large cell
      neuroendocrine carcinoma is the recognition of its light-microscopic
      neuroendocrine features. In consequence it must be distinguished not only from
      atypical carcinoid or small cell lung carcinoma (SCLC), but also from poorly
      differentiated carcinoma. Immunohistochemistry is important for the diagnosis of
      this entity but also for nonsmall cell lung carcinoma with neuroendocrine
      differentiation (of which 1 case was detected in our series) There was agreement
      on the diagnosis of small cell carcinomas in all but one case. The results
      indicate the excellent reproducibility of the WHO classification.

PMID- 12508139
TI  - Clinical experience of surgical therapy in 207 patients with thoracic hydatidosis
      over a 12-year-period.
AB  - PRINCIPLES: Hydatid disease is the most severe helminthic zoonosis, with a major
      medical, social, and economic impact in Turkey. The aim of this study was to
      evaluate retrospectively 207 patients diagnosed with hydatid cyst and treated
      surgically in our department between January 1990 and December 2001. METHODS:
      Hundred and ninety three patients were male and 14 female. They ranged in age
      from 19 to 72 years (mean 25.3 years). The most common presenting symptoms were
      cough, expectoration and chest pain. The surgical approach was thoracotomy in 198
      patients, bilateral staged thoracotomies in 5 patients, median sternotomy in one
      patient and video-assisted thoracic surgery in 3 patients. RESULTS: Hundred and
      thirty eight of the 265 intrapulmonary cystic lesions were found in the right
      lung and 127 in the left lung. Intrathoracic extrapulmonary cystic lesions were
      detected in 13 patients. 38 patients also had cystic lesions in the liver.
      Conservative surgical procedures were adopted except for small wedge resections
      in 8 patients, segmentectomy in 4 patients and lobectomy in one. Operative and
      postoperative mortality was nil. Albendazole treatment was given to patients who
      had multiple intrathoracic cysts or additional hepatic cysts after 1994.
      CONCLUSIONS: Our preferred surgical techniques for removal of cysts were
      conservative surgical procedures such as enucleation of cysts or removal by
      cystotomy. Radical procedures such as pneumonectomy, lobectomy and segmentectomy
      should be avoided as far as possible.

PMID- 12508140
TI  - Association of severe respiratory syncytial virus bronchiolitis with interleukin
      4 and interleukin-4 receptor alpha polymorphisms.
AB  - The association of variants of genes encoding interleukin (IL)-4 and the IL-4
      receptor alpha chain (IL-4Ralpha) with respiratory syncytial virus (RSV)
      bronchiolitis was examined in hospitalized infants. Polymorphisms in IL-4 (C
      590T) and IL-4Ralpha (I50V and Q551R) were genotyped by restriction fragment
      length polymorphism analysis. Control subjects included parents of the
      hospitalized children (for the transmission/disequilibrium test), and a random
      population sample (for the case-control study). Results were also analyzed in a
      combination of these 2 tests, using Fisher's method. The IL-4 590T allele was
      found more frequently among children hospitalized with RSV than expected in the
      case-control (odds ratio [OR], 1.43; P=.04) and combination (OR, 1.41; P=.02)
      tests. Among children who were >6 months old when they were hospitalized,
      compared with the control group or with the <6 months old who were hospitalized
      for RSV infection, higher frequencies of both the IL-4 590T allele and the IL
      4Ralpha R551 allele were found. These results indicate that gain-of-function
      variants of T helper type 2 cytokine genes may play a role in increasing the
      severity of RSV disease, which appears more pronounced after the first half-year
      of life.

PMID- 12508141
TI  - Antibody reactivity to latent and lytic antigens to human herpesvirus-8 in
      longitudinally followed homosexual men.
AB  - Tests for human herpesvirus-8 (HHV-8) often disagree on which individuals are
      infected. To evaluate HHV-8 antibody changes over many years, 245 homosexual men
      enrolled in a prospective study between 1982 and 1999 were studied. Samples
      collected annually were evaluated by immunofluorescence to HHV-8 latent nuclear
      antigen and by an ELISA for antibody against the HHV-8 lytic antigen K8.1. When
      positive, samples from most subjects were persistently reactive in both assays.
      Titers to both lytic and latent antibodies increased for many years, usually in
      parallel, and were higher in human immunodeficiency virus-infected men. The
      increasing titers and expanding epitope recognition suggest ongoing, low-grade
      replication of HHV-8. Use of multiple assays is important in determining
      prevalence in asymptomatic populations. Because persons with more advanced
      infections have higher antibody titers, they are easier to detect, which may skew
      our understanding of the epidemiology of HHV-8.

PMID- 12508142
TI  - Herpes simplex virus type 2 infection as a risk factor for human immunodeficiency
      virus acquisition in men who have sex with men.
AB  - The association of human immunodeficiency virus (HIV) acquisition with herpes
      simplex virus type 2 (HSV-2) was assessed among men who have sex with men (MSM)
      in a nested case-control study of 116 case subjects who seroconverted to HIV
      during follow-up and 342 control subjects who remained HIV seronegative,
      frequency-matched by follow-up duration and report of HIV-infected sex partner
      and unprotected anal sex. The baseline HSV-2 seroprevalence was higher among case
      (46%) than control (34%) subjects (P=.03); the HSV-2 seroincidence was 7% versus
      4% (P=.3). Only 15% of HSV-2-infected MSM reported herpes outbreaks in the past
      year. HIV acquisition was associated with prior HSV-2 infection (odds ratio [OR],
      1.8; 95% confidence interval [CI], 1.1-2.9), reporting >12 sex partners (OR, 2.9;
      95% CI, 1.4-6.3), and reporting fewer herpes outbreaks in the past year (OR, 0.3;
      95% CI, 0.1-0.8). HSV-2 increases the risk of HIV acquisition, independent of
      recognized herpes lesions and behaviors reflecting potential HIV exposure. HSV-2
      suppression with antiviral therapy should be evaluated as an HIV prevention
      strategy among MSM.

PMID- 12508143
TI  - Influence of plasma viremia on defects in number and immunophenotype of blood
      dendritic cell subsets in human immunodeficiency virus 1-infected individuals.
AB  - Dendritic cells (DCs) are postulated to be involved in transmission of human
      immunodeficiency virus (HIV) type 1 to T cells and in stimulation of HIV-1
      specific cell-mediated immunity. Blood DCs have been categorized as myeloid (mDC)
      and plasmacytoid (pDC) subsets, on the basis of differences in phenotype and
      function. Blood DC subset numbers and expression of costimulatory molecules and
      HIV-1 coreceptors on DCs were measured in the blood of treated and untreated HIV
      1-infected subjects and uninfected control subjects. Absolute numbers of mDCs and
      pDCs were lower in HIV-1-infected subjects than in control subjects, most
      significantly in those with active HIV-1 replication. Increased surface
      expression of costimulatory molecules was observed on both DC subsets in subjects
      with HIV-1 viremia. Highly active antiretroviral therapy suppression of plasma
      viremia resulted in increases in blood DC numbers and decreases in DC
      costimulatory molecule expression. These findings further define the impact of
      HIV-1 replication on blood DC subsets in vivo.

PMID- 12508144
TI  - Predictive value of provirus load and DNA human immunodeficiency virus genotype
      for successful abacavir-based simplified therapy.
AB  - Of 75 human immunodeficiency virus (HIV) type 1-infected patients successfully
      responding to 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus 1
      protease inhibitor (PI), 55 started a simplified abacavir (ABC)-based triple NRTI
      regimen. Influences of DNA load and DNA reverse-transcriptase (RT) mutations on
      virological responses were assessed at month 6 after initiation of therapy.
      Baseline heterogeneity was observed: peripheral blood mononuclear cell (PBMC)
      genotyping showed 31% RT mutations with 1-5 NRTI-related mutations, 78% protease
      mutations had 1-5 PI-related mutations; and HIV-1-DNA levels were 1.8-3.5 log(10)
      copies/10(6) PBMC. Outcomes for 49 patients on a regimen of 2 NRTIs plus ABC were
      as follows: 22 successes, 10 blips ("blip" defined as intermittent plasma HIV-1
      RNA levels between 50 and 100 copies/mL and a return to an undetectable level),
      and 17 failures, whereas, for patients continuing on a regimen of 2 NRTIs plus 1
      PI, there were 19 successes and 1 blip. Previous treatment regimens, baseline
      provirus level, and PBMC genotype predicted virological outcome.

PMID- 12508145
TI  - Role of heme oxygenase-1 in morphine-modulated apoptosis and migration of
      macrophages.
AB  - We examined the role of heme oxygenase (HO)-1 in morphine-induced decrease in
      macrophage migration. Morphine promoted expression of HO-1 in murine macrophages.
      Morphine-receiving mice (MRCs) showed decreased (P<.001) macrophage migration and
      increased (P<.001) occurrence of macrophage apoptosis. In in vitro studies,
      peritoneal macrophages harvested from MRCs also showed decreased (P<.001)
      migration, compared with those from control mice. Bone marrow cells isolated from
      MRCs showed not only decreased (P<.001) migration but also increased apoptosis.
      Pretreatment of MRCs with hemin not only decreased migration of macrophages
      further but also enhanced the apoptosis of peritoneal macrophages. On the other
      hand, pretreatment of MRCs with zinc protoporphyrin attenuated the effect of
      morphine on both macrophage migration and the occurrence of apoptosis. In in
      vitro studies, pretreatment of macrophages with hemin exacerbated morphine
      induced apoptosis, whereas pretreatment with zinc protoporphyrin attenuated
      morphine-induced macrophage apoptosis.

PMID- 12508146
TI  - Effects of IC14, an anti-CD14 antibody, on coagulation and fibrinolysis during
      low-grade endotoxemia in humans.
AB  - To determine the role of CD14 in lipopolysaccharide (LPS)-induced effects on
      coagulation and fibrinolysis in humans, 16 healthy subjects received an
      intravenous injection of LPS preceded by intravenous IC14, a recombinant chimeric
      monoclonal antibody against human CD14, or placebo. LPS-induced coagulation
      activation (tissue-factor mRNA in whole blood cells and plasma concentrations of
      F1+2) was not influenced by IC14, whereas the antibody reduced the increase in
      thrombin-antithrombin complexes and soluble fibrin. LPS injection also was
      associated with an early activation of fibrinolysis (plasma concentrations of
      tissue-type plasminogen activator and plasmin-alpha(2)-antiplasmin complexes),
      followed by an inhibitory response (plasminogen activator inhibitor type 1),
      which were attenuated by IC14. Furthermore, LPS reduced thrombin-activatable
      fibrinolysis-inhibitor antigen levels and increased soluble thrombomodulin
      levels, which were not influenced by IC14. These results suggest that different
      hemostatic responses during endotoxemia may proceed via CD14-dependent and 
      independent pathways.

PMID- 12508148
TI  - Orally administered recombinant human interleukin-11 is protective in
      experimental neutropenic sepsis.
AB  - Recombinant human interleukin (IL)-11 is a multifunctional cytokine with
      hematopoietic, immunomodulatory, and epithelial cell protective activities. IL
      11alpha receptors are expressed on the luminal surface of intestinal epithelial
      cells. It was hypothesized that orally administered IL-11 would prevent mucosal
      damage and protect against microbial invasion in a neutropenic rat model of gram
      negative sepsis. IL-11 was administered daily by enteric, coated multiparticle
      pellets over the course of chemotherapy-induced neutropenia. Compared with the
      placebo group, IL-11-treated rats retained mucosal mass and had prolonged
      survival time, reduced pathologic changes, and reduced systemic levels of
      bacterial endotoxin and concentrations of Pseudomonas aeruginosa in target
      tissues. Enterocyte messenger RNA levels for tumor necrosis factor-alpha and
      interferon-gamma revealed that oral IL-11 reduced but did not prevent increased
      expression of these cytokine genes. These results indicate that orally
      administered IL-11 may preserve epithelial cell integrity in the presence of
      cytoreductive chemotherapy. This may represent a new treatment strategy for the
      prevention of infection in neutropenic hosts.

PMID- 12508147
TI  - Interferon-gamma enhances the pulmonary CXC chemokine response to intratracheal
      lipopolysaccharide challenge.
AB  - CXC chemokines are major chemoattractants for pulmonary polymorphonuclear
      leukocyte (PMNL) recruitment. To study the effects of interferon (IFN)-gamma on
      the pulmonary chemokine response to lipopolysaccharide (LPS) challenge, rats were
      treated with intratracheal IFN-gamma (1x10(5) U/rat) 24 h before an intratracheal
      LPS (100 microg/rat) challenge. Intratracheal LPS caused significant increases in
      both cytokine-induced neutrophil chemoattractant (CINC) and macrophage
      inflammatory protein-2 in bronchoalveolar lavage (BAL) fluid and pulmonary PMNL
      recruitment. IFN-gamma enhanced these responses. IFN-gamma also increased LPS
      induced tumor necrosis factor (TNF)-alpha in BAL fluid. LPS-induced TNF-alpha and
      CINC mRNA expression in alveolar macrophages was increased by IFN-gamma. CD11b/c
      and CD18 expression on circulating PMNLs was not affected by IFN-gamma, nor was
      the chemotaxis of these cells. IFN-gamma increases the pulmonary CXC chemokine
      response, which may serve as one mechanism underlying enhanced PMNL delivery into
      the lung.

PMID- 12508149
TI  - Staphylococcus aureus express unique superantigens depending on the tissue
      source.
AB  - A comprehensive analysis of Staphylococcus aureus superantigen (SAG) genes was
      undertaken in isolates from a major hospital and compared with isolates from
      patients with toxic shock syndrome (TSS). Polymerase chain reaction (PCR)
      analysis included recently discovered SAGs. Staphylococcal enterotoxin (SE) G and
      SEI were uniquely expressed in genital isolates. Genital isolates were similar to
      TSS isolates, although the latter frequently expressed TSS toxin 1. Both had a
      high frequency of SEG/SEI and a high number of SAG genes per bacterium. Detection
      of an SAG gene by PCR correlated with positive results in functional assays for
      SAG activity. Levels of serum antibodies to SEG and SEI, but not to other
      superantigens, were higher in healthy women than in men and served as an
      independent measure of the higher frequency of exposure to SEG/SEI among women.
      Together, the data suggest a role for SEG/SEI or closely linked genes in the
      adaptation of S. aureus to the genital mucosa environment.

PMID- 12508150
TI  - Human lactoferrin impairs virulence of Shigella flexneri.
AB  - Lactoferrin is a glycoprotein present in most human mucosal secretions, including
      human milk. Lactoferrin is bacteriostatic in low iron media and, in some
      settings, bactericidal. Lactoferrin impairs ability of Shigella flexneri serotype
      5 strain M90T to invade HeLa cells. To determine the mechanism by which
      lactoferrin decreases invasiveness of Shigella organisms, its effect on the major
      virulence proteins responsible for bacterial uptake by host cells was evaluated.
      Lactoferrin induced degradation of invasion plasmid antigens IpaB and, to a
      lesser extent, IpaC, the key proteins responsible for bacteria-directed
      phagocytosis by mammalian cells. The lipid A-binding N-terminal portion of
      lactoferrin (residues 1-33) induces release of invasion antigens but does not
      induce degradation of IpaBC. Lactoferrin does not directly degrade previously
      released invasion plasmid antigens but works by making IpaBC susceptible to
      breakdown by surface-expressed protease(s).

PMID- 12508151
TI  - A 4-year study of the epidemiology of Vibrio cholerae in four rural areas of
      Bangladesh.
AB  - How Vibrio cholerae spreads around the world and what determines its seasonal
      peaks in endemic areas are not known. These features of cholera have been
      hypothesized to be primarily the result of environmental factors associated with
      aquatic habitats that can now be identified. Since 1997, fortnightly surveillance
      in 4 widely separated geographic locations in Bangladesh has been performed to
      identify patients with cholera and to collect environmental data. A total of 5670
      patients (53% <5 years of age) have been studied; 14.3% had cholera (10.4% due to
      V. cholerae O1 El Tor, 3.8% due to O139). Both serogroups were found in all
      locations; outbreaks were seasonal and often occurred simultaneously. Water-use
      patterns showed that bathing and washing clothes in tube-well water was
      significantly protective in two of the sites. These data will be correlated with
      environmental factors, to develop a model for prediction of cholera outbreaks.

PMID- 12508152
TI  - Human T lymphocyte response to Borrelia burgdorferi infection: no correlation
      between human leukocyte function antigen type 1 peptide response and clinical
      status.
AB  - We tested the hypothesis that cross-reactivity between the outer surface protein
      A (OspA) of Borellia burgdorferi and human leukocyte function antigen (LFA) type
      1 mediates chronic autoimmune sequelae of Lyme disease. T cell response was
      studied in subjects with Lyme disease presenting with erythema migrans alone
      (n=36), erythema migrans with neurological disease (n=12), and chronic Lyme
      disease syndrome (n=20), as well as healthy control subjects from Lyme-endemic
      (n=50) and -nonendemic (n=18) regions. Antigens included recombinant OspA and
      OspC (all strain B31) and human LFA-1 peptide (IYVIEGTSKQDLTSF). Proliferation to
      OspA was detected in 11 (28%) of 39 of subjects presenting with erythema migrans,
      which increased to 50% at 4 weeks of follow-up. Reactivity to OspA and LFA-1 was
      significantly correlated (P<.001) and was observed in 18 (78%) of 23 of OspA
      responsive subjects. However, there was no correlation between T cell response to
      human LFA-1 peptide and clinical status.

PMID- 12508153
TI  - Prevention of Haemophilus influenzae type b (Hib) meningitis and emergence of
      serotype replacement with type a strains after introduction of Hib immunization
      in Brazil.
AB  - Surveillance for Haemophilus influenzae meningitis cases was performed in
      Salvador, Brazil, before and after introduction of H. influenzae type b (Hib)
      immunization. The incidence of Hib meningitis decreased 69% during the 1-year
      period after initiation of Hib immunization (from 2.62 to 0.81 cases/100,000
      person-years; P<.001). In contrast, the incidence for H. influenzae type a
      meningitis increased 8-fold (from 0.02 to 0.16 cases/100,000 person-years;
      P=.008). Pulsed-field gel electrophoretic analysis demonstrated that H.
      influenzae type a isolates belonged to 2 clonally related groups, both of which
      were found before Hib immunization commenced. Therefore, Hib immunization
      contributed to an increased risk for H. influenzae type a meningitis through
      selection of circulating H. influenzae type a clones. The risk attributable to
      serotype replacement is small in comparison to the large reduction in Hib
      meningitis due to immunization. However, these findings highlight the need to
      maintain surveillance as the use of conjugate vaccines expands worldwide.

PMID- 12508154
TI  - Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin
      attenuation.
AB  - The tuberculosis (TB) vaccine bacille Calmette-Guerin (BCG) is a live attenuated
      organism, but the mutation responsible for its attenuation has never been
      defined. Recent genetic studies identified a single DNA region of difference,
      RD1, which is absent in all BCG strains and present in all Mycobacterium
      tuberculosis (MTB) strains. The 9 open-reading frames predicted within this 9.5
      kb region are of unknown function, although they include the TB-specific
      immunodominant antigens ESAT-6 and CFP-10. In this study, RD1 was deleted from
      MTB strain H37Rv, and virulence of H37Rv:DeltaRD1 was assessed after infections
      of the human macrophage-like cell line THP-1, human peripheral blood monocyte
      derived macrophages, and C57BL/6 mice. In each of these systems, the
      H37Rv:DeltaRD1 strain was strikingly less virulent than MTB and was very similar
      to BCG controls. Therefore, it was concluded that genes within or controlled by
      RD1 are essential for MTB virulence and that loss of RD1 was important in BCG
      attenuation.

PMID- 12508155
TI  - Adrenocortical hormones and interleukin patterns in paracoccidioidomycosis.
AB  - The functional status of adrenocortical hormones and their relationship to the
      pattern of inflammatory cytokines in paracoccidioidomycosis were investigated in
      a prospective study. Patients were evaluated before treatment and 1 and 6 months
      after receiving antifungal therapy. Interleukin (IL)-1beta, IL-6, and tumor
      necrosis factor-alpha plasma levels, C-reactive protein (CRP) concentrations, and
      erythrocyte sedimentation rate (ESR) were significantly higher in untreated
      patients than in control subjects. After 6 months of treatment, levels of the 3
      cytokines, CRP concentrations, and the ESR decreased significantly. Both baseline
      and stimulated adrenocorticotropic hormone and cortisol plasma levels were not
      different between patients and control subjects. In contrast, adrenal androgen
      dehydroepiandrosterone sulfate (DHEA-S) plasma levels were significantly lower in
      patients than in sex- and age-matched control subjects. There was a significant
      inverse correlation between DHEA-S and IL-6 plasma levels. This finding may be of
      pathogenetic significance in this disease and in other inflammatory states.

PMID- 12508156
TI  - Serum immunoglobulin G4 antibodies to the recombinant antigen, Ll-SXP-1, are
      highly specific for Loa loa infection.
AB  - The clinical manifestations and geographic distribution of loiasis overlap with
      those of other human filarial parasites, presenting challenges in the specific
      diagnosis of loiasis that may lead to delays in appropriate therapy. A
      recombinant antigen (Ll-SXP-1), preferentially recognized by serum samples from
      experimentally infected rhesus monkeys, was identified from a Loa loa L3 cDNA
      library. IgG4 antibody reactivity to purified Ll-SXP-1 was assessed by means of
      ELISA, using serum samples from patients with loiasis, lymphatic filariasis,
      onchocerciasis, mansonellosis, or other helminthiases and healthy control
      subjects. The assay was 56% sensitive and 98% specific for loiasis. Antibody
      reactivity was detectable before microfilaremia in experimentally infected rhesus
      monkeys and declined (but did not disappear) after diethylcarbamazine therapy in
      infected patients. IgG4 antibodies to recombinant Ll-SXP-1 are a highly specific
      marker of L. loa infection and may be useful for the diagnostic evaluation of
      persons with filariasis of unclear etiology.

PMID- 12508157
TI  - Long-term immunogenicity and efficacy of universal hepatitis B virus vaccination
      in Taiwan.
AB  - The long-term immunogenicity of universal hepatitis B virus (HBV) vaccine is
      seldom studied in large-scale prospective community-based populations, especially
      in adolescents. This study enrolled 1200 children aged 7 years with complete HBV
      immunization in infancy and determined HBV surface antigen (HBsAg), its antibody
      (anti-HBs), and HBV core antibody (anti-HBc) annually until the children were
      aged 14 years. Eleven children had new HBV infections with anti-HBc positivity as
      the only marker. None became positive for HBsAg or had detectable HBV DNA by
      polymerase chain reaction. The percentage of protective anti-HBs in 951 children
      without booster vaccination gradually decreased from 71.1% at age 7 years to
      37.4% at age 12 years. Only 1 of the 200 children in the booster group and 2 of
      the 258 children in the nonbooster group developed new anti-HBc positivity. The
      results suggest that routine booster vaccination may not be required to provide
      protection against chronic HBV infection before age 15 years.

PMID- 12508158
TI  - Ganciclovir-resistant cytomegalovirus disease after allogeneic stem cell
      transplantation: pitfalls of phenotypic diagnosis by in vitro selection of an
      UL97 mutant strain.
AB  - A 9-month posttransplantation course of an allogeneic stem-cell transplant
      recipient (human cytomegalovirus [HCMV] serostatus, donor positive/recipient
      negative), in whom ganciclovir (GCV) resistance developed (UL97 mutations M460V,
      L595S, and C603W) on day 164 after transplantation and who developed HCMV
      retinitis and fatal HCMV encephalitis is presented. Virus strains isolated from
      secondary cultures were analyzed by UL97 restriction assays and sequencing and
      were compared with primary DNA extracts of the same specimens, which resulted in
      molecular proof of an initial HCMV strain-specific in vitro selection of the in
      vivo nondominant UL97 L595S-C603 mutant strain from 3 viral variants present in
      vivo. In addition, compartmentalization of virus present in blood and
      cerebrospinal fluid was found. The influence of rapidly increasing plasma virus
      load (to >10(6) copies/mL) and oral administration of GCV on the emergence of GCV
      resistance is shown. These findings have strong implications for the diagnosis of
      HCMV drug resistance.

PMID- 12508159
TI  - Prognostic value of baseline human immunodeficiency virus type 1 DNA measurement
      for disease progression in patients receiving nucleoside therapy.
AB  - Human immunodeficiency virus (HIV) type 1 DNA assay data were obtained at
      baseline from 111 HIV-1-positive subjects who were treated with nucleosides.
      Higher baseline DNA level, HIV-1 RNA level, and infectious titer were comparably
      associated with an increased hazard of disease progression (each P<.03). Only DNA
      level was significantly associated with survival (adjusted hazard ratio for 1
      log(10) higher level, 3.99; 95% confidence interval, 1.44-11.09; P=.008).

PMID- 12508160
TI  - A pilot study of cidofovir in patients with kaposi sarcoma.
AB  - A clinical trial was conducted to test the activity of cidofovir (CDV), a drug
      with in vitro activity against Kaposi sarcoma (KS)-associated herpesvirus (KSHV),
      in KS. Five patients with human immunodeficiency virus-associated KS (4 receiving
      antiretroviral therapy) and 2 patients with classical KS were administered CDV (5
      mg/kg/dose) weekly for 2 weeks and then every other week. All 7 patients had
      progression of their KS at a median of 8.1 weeks (range, 5-27 weeks). Skin biopsy
      specimens of KS lesions showed no change in expression of latent or early lytic
      genes, but, in the 1 assessable patient, there was decreased expression of a late
      lytic gene. There was no decrease in the virus load of KSHV in peripheral blood
      mononuclear cells. This study does not provide proof of principle for the
      treatment of KS with CDV. However, it remains possible that antiherpesvirus
      therapy can be developed for herpes-induced tumors.

PMID- 12508161
TI  - Induction of apoptosis of human brain microvascular endothelial cells by shiga
      toxin 1.
AB  - Brain injury is the most frequent cause of mortality among patients with the
      hemolytic-uremic syndrome. Human brain endothelial cells (HBECs) are resistant to
      Escherichia coli-derived Shiga toxin (Stx); however, inflammatory cytokines
      markedly increase HBEC sensitivity to Stx cytotoxicity. HBECs were exposed to
      tumor necrosis factor (TNF)-alpha, with and without Stx-1, and cell survival,
      (125)I-Stx1 binding, globotriaosylceramide content, cell necrosis, and cell
      apoptosis levels were determined. TNF greatly increased Stx-1 cytotoxicity,
      primarily through induction of apoptosis, in HBEC.

PMID- 12508162
TI  - A new method for culturing Plasmodium falciparum shows replication at the highest
      erythrocyte densities.
AB  - Plasmodium falciparum replicates poorly in erythrocyte densities greater than a
      hematocrit of 20%. A new method to culture the major malaria parasite was
      developed by using a hollow fiber bioreactor that preserves healthy erythrocytes
      at hematocrit up to 100%. P. falciparum replicated equally well at all densities
      studied. This method proved advantageous for large-scale preparation of
      parasitized erythrocytes (and potentially immunogens thereof), because high
      yields ( approximately 10(10) in 4 days) could be prepared with less cost and
      labor. Concomitantly, secreted proteins were concentrated by molecular sieving
      during culture, perhaps contributing to the parasitemic limit of 8%-12% with the
      3D7 strain. The finding that P. falciparum can replicate at packed erythrocyte
      densities suggests that this system may be useful for study of the pathogenesis
      of fatal cerebral malaria, of which one feature is densely packed blood cells in
      brain microvasculature.

PMID- 12508163
TI  - [Stem cells. What is their future in regenerative medicine?].
AB  - Ethical considerations on the use of embryonic stem cells have been emphasized in
      many countries where their study in experimental and clinical Medicine is
      prohibited. On the contrary, different approaches have been used to purify adult
      stem cells given that preliminary data demonstrate their beneficial use in some
      pathological conditions. The debate on the use of stem cells in regenerative
      medicine is open.

PMID- 12508164
TI  - [In search of renal stem cells].
AB  - The therapeutic potential of stem cell research is very promising. Although
      arising ethical questions, especially in the field of embryonic stem cells (ES),
      it is astonishing how, in the last few years, the potential application of stem
      cells for treating proliferative as well as degenerative diseases, is becoming
      increasingly evident. It was recently demonstrated that somatic stem cells showed
      unexpected plasticity similar to ES. In fact, if somatic stem cells are exposed
      to proper stimuli they can differentiate into a multitude of cell types that may
      be different from those of the tissue they belong to. In addition, it was
      recently demonstrated that circulating blood stem cells, probably of bone marrow
      origin, were recruited at the sites of injury to regenerate or repair damaged
      tissues. Very little is known about renal stem cells. Although the great capacity
      of the kidney to regenerate injured nephrons is well established, renal somatic
      stem cells have yet to be identified. The question we are now faced with is
      whether renal stem cells exist and, if they do exist, where do they reside. In
      the attempt to answer this question, the present review will focus on the
      achievements both in the fields of somatic stem cells and renal embryogenesis and
      in the field of renal repair and regeneration mechanisms.

PMID- 12508165
TI  - [Anti-GM1 and anti-sulphatide antibodies in systemic idiopathic vasculitis,
      systemic lupus erythematosus and mixed cryoglobulinaemia: Serum detection and
      clinical and electrophysiologic correlations].
AB  - BACKGROUND: In the last two decades increasing interest has been focused on the
      association between autoimmune polyneuropathies and high titers of anti-nervous
      serum autoantibodies. High titer of IgG anti-GM1 antibody could be detected in
      Guillain Barre' syndrome and in chronic painful axonal sensory immune-mediated
      polyneuropathy. The possible occurrence of anti-nervous autoantibodies in
      autoimmune diseases not limited to the nervous system is still under study.
      METHODS: We evaluated 29 patients with systemic lupus erythematosus (SLE), 19
      with biopsy-proven renal involvement, 28 patients with mixed IgM-K/IgG polyclonal
      cryoglobulinaemia (18 with glomerulonephritis) and 19 with small-sized vessel
      ANCA-associated vasculitis (12 with renal involvement) by using a sensitive
      immunoenzyme method of autoantibody detection. RESULTS: Compared to controls
      (1/176+/-1/205; 1:204+/-1:103), we found a significant increase in plasma IgM and
      IgG anti-GM1 titers (1:643+/-1:531; 1:444+/-1:309) in SLE patients (p<0.0001). We
      also found IgM (1:3032+/-1:2844) and IgG (1:1560) anti-sulphatide titers to be
      higher than the control group (p<0.0001). Mean plasma IgM and IgG anti-GM1 titers
      of the cryoglobulinaemic patients were 1:524+/-1:403 and 1:501+/-1:415,
      respectively, once again higher than the controls (p<0.0001). Mean plasma IgM and
      IgG anti-sulphatide titers in this group were 1:1864+/-1:1189 and 1:1350
      (p<0.0001). We found idiopathic systemic vasculitis patients to have
      significantly increased levels of anti-sulphatides IgG class autoantibodies
      (1:1400; p<0.0001). We found no correlation with the serologic markers for
      vasculitis or the clinical or histologic extent of renal involvement.
      Electrophysiologic studies revealed that in 38% of SLE patients (p<0.005), 61% of
      cryoglobulinaemic patients (p<0.01) and 42% of ANCA-related vasculitic patients
      (p<0.01) the abnormal titers of antineuronal antibodies were associated with
      clinical or subclinical evidence of neuropathy. CONCLUSIONS: In patients with
      systemic idiopathic or secondary vasculitis anti-GM1 and anti-sulphatide
      antibodies can frequently be found. Their presence should prompt an accurate
      neurological examination because these serologic abnormalities are significantly
      associated with neurologic, often subclinical, involvement. Antineuronal
      reactivity might be the epiphenomenon of primary phylogistic damage, which
      exposes normally segregated neuronal epitopes or be directly involved in
      triggering neurological injury.

PMID- 12508166
TI  - [Dialysis in the elderly].
AB  - Assuming >/= 75 years old as the age limit to define dialysis in the elderly, the
      incidence in this group of patients is progressively increasing in most dialysis
      units, with an annual growth of 8 to 16%, and represents 20 to 33% of the overall
      population being affected. The prevalence of the elderly dialysis group is also
      high, 14 to 20%, in the main literature casistics. Vascular nephropathies, 13 to
      50%, represent the major cause of end-stage renal disease, followed by diabetes,
      11 to 37%. First year survival rate is an acceptable 52 to 82%, whereas the fifth
      year value is on average 20 %, also due to the high baseline mortality in these
      patients. The death causes are mainly cardiac related and represent 45% of the
      overall mortality. The main prognostic factors are frequency and severity of
      comorbid factors, in addition to nutritional indexes that are particularly
      important in this age group. Dialysis dose and treatment time are not related to
      mortality. Haemodialysis and peritoneal dialysis complement each other to allow
      the best results. The survival rate, however, is usually better with
      haemodialysis, especially in old diabetic patients and after some years of
      treatment. Vascular access, intradialytic hypotension, cardiopathy, intestinal
      bleeding and amyloidotic arthropathy represent the more critical aspects of
      dialysis in the elderly, while the quality of life is sometimes unexpectedly
      good.

PMID- 12508167
TI  - [Local therapy with platelet-derived growth factors for chronic diabetic ulcers
      in haemodialysis patients].
AB  - BACKGROUND: The increasing number of diabetic patients who need dialysis
      treatment is the cause for the growing interest of nephrologists in ulcers of the
      lower limbs. It has been reported that platelet-derived growth factors, such as
      PDGF and TGF beta 1, are able to heal skin lesions due to diabetes. Therefore, a
      platelet gel (PG) has been developed to locally treat foot ulcers with a limited
      number of applications (3+/-1.7). METHOLOGY AND PATIENTS: The PG is a mix of
      concentrated platelets and cryoprecipitate activated by batroxobin in the
      presence of calcium chloride (or gluconate) that must be applied to the wound for
      three days. The surgeon and the dermatologist should then plan successive
      treatments because the necrotic tissue needs to be removed. We treated a 62-year
      old diabetic man, who has been under treatment with insulin since the age of 36
      and has been dialysed for three years. His right lower leg was amputated and he
      developed a chronic left foot ulcer that resulted in many septic episodes. His
      ulcer recovered in two months after 8 PG applications. CONCLUSIONS: Conventional
      therapy is not successful in 15-20% of diabetic feet. Uraemia and malnutrition
      may represent important risk factors for foot ulcers in diabetic patients who
      need advanced technology to stimulate tissue repair. The use of platelet growth
      factor may ameliorate ulcer healing thus reducing disease-associated morbidity
      and lowering health care costs.

PMID- 12508168
TI  - [Xerostomia and Xerophthalmia in haemodialysis patients].
AB  - BACKGROUND: A reduction in salivary and lachrymal secretion has been described in
      many pathologies; however, such alterations have not been described in patients
      with renal failure. This study was designed to estimate the frequency of
      alterations in salivary and lachrymal secretion in haemodialysed patients.
      PATIENTS ABD METHODS: We studied 63 haemodialysed patients and 23 healthy control
      subjects. In all of them we tested salivary secretion (Saxon test), lachrymal
      secretion (Shirmer test) as well as the presence of symptoms of xerostomia and
      xerophthalmia. In a subgroup of patients We investigated any evidence of ocular
      lesions and tissue damage of salivary glands (histopathology). We also tested the
      correlation between salivary and lachrymal secretion and autonomic nervous system
      function. Furthermore, we also studied the association between xerostomia and
      xerophthalmia and serum auto antibodies (anti nuclear, anti-Ro (SS-A), anti-La
      (SS-B)) and anti HCV antibodies. RESULTS: On average salivary and the lachrymal
      secretion was markedly reduced in uraemic patients compared with healthy
      controls. We found the alterations in salivary glands function to be strongly
      related to salivary glands fibrosis and atrophy and independent of amyloid
      accumulation. On the other hand, we observed that xerostomia and xerophthalmia
      were unrelated to autonomic dysfunction as well as to HCV infection and
      circulating auto antibodies. Moreover, xerophthalmia was frequently associated
      with evidence of corneal damage. CONCLUSIONS: Reduced salivary and lachrymal
      secretion is frequent in uraemic patients. Such alterations are often
      asymptomatic and could be an expression of the accelerated age-dependent decline
      in glandular function and the attendant fibrosis and atrophy.

PMID- 12508169
TI  - [Cytokines and chemokines in nephropathies and renal transplant].
AB  - Cytokines are soluble factors that are critical for the pathophysiology of the
      immune system and exhibit other important functions. Cytokines produced by type 1
      helper T (Th1) lymphocytes, such as interferon (IFN)-g, play a pathogenic role in
      proliferative glomerulonephrites (GN), as well as in the acute rejection of
      kidney allografts. Cytokines produced by type 2 Th (Th2) lymphocytes, such as
      interleukin (IL)-4, IL-5, and IL-13), predominate in membranous GN and in minimal
      change disease. More recently, the pathogenic role of some members of the family
      of chemotactic cytokines (chemokines) in different nephropathies and in the acute
      and chronic rejection of kidney allografts has also been demonstrated. In
      particular, the chemokine MCP1/CCL2 has been found to be expressed in the kidneys
      of subjects with tubulo-interstitial nephritis and seems to play an important
      role in the sclerotic evolution of both inflammatory and metabolic nephropathies.
      Interactions between IP-10/CXCL10, Mig/CXCL9 and I-TAC/CXCL11 and their shared
      receptor, CXCR3, seem to be responsible not only for Th1 cell infiltration in
      acute allograft rejection and in proliferative GN, but also for mesangial cell
      proliferation typical of the latter condition. In proliferative GN, mesangial
      cells indeed express both these chemokines and their receptor. Moreover, in the
      kidneys of subjects suffering from chronic allograft nephropathy, IP-10/CXCL10,
      Mig/CXCL9 and I-TAC/CXCL11 have been found to be produced by and to act on the
      proxymal tubular epithelial cells, endothelial cells and smooth muscle vessel
      cells, suggesting their possible role in both the genesis of tubular atrophy and
      allograft artheriosclerosis.

PMID- 12508170
TI  - [Renal transplantation and malignancies: A single-centre experience (25 years)].
AB  - BACKGROUND: The prevalence of post-transplant malignancies, in renal transplant
      recipients, is higher than that expected in age and sex-matched controls from the
      general population, and there is a markedly increased incidence of certain
      cancers. METHODS: In 1137 renal transplant recipients (1020 from cadaveric and
      117 from living donors, M/F 771/366) performed at the S. Orsola Renal
      Transplantation Centre since 10/1976 to 9/2001, we studied the post-transplant
      cancer prevalence, the correlation between cancer prevalence and population
      characteristics, the risk factors (smoke, cancer history, positive HBsAg and
      antiHCV infection) and the immunosuppressive therapy. RESULTS AND CONCLUSIONS:
      The prevalence of malignancies was 3.86% (52 malignancies in 44 patients). The
      period between transplant and diagnosis of malignant disease was 59 +/- 85
      months. Skin cancer was the most common (n=16; 30.7%), followed by
      lymphoproliferative disorders (n=8; 15.4%), Kaposi s sarcoma (n=6; 11.5%),
      uterine cancer (n=6; 11.5%), renal carcinoma of native kidney (n=5; 9.6%), cancer
      of breast/stomach/pancreas and urinary bladder (n=2; 3.8%) and other cancers
      (n=5; 9.6%). The mean duration of dialysis before transplantation was longer in
      cancer patients (41+/- 32.1 vs. 33.5 +/- 32.4 months). We found a correlation
      between types of malignancies and viral infection in NH-lymphoma (EBV positive
      4/4) and skin cancer (HZV positive 13/16). We also detected a correlation between
      Aza and skin cancer (16/22) and CyA and lymphoproliferative disorders (7/8).

PMID- 12508171
TI  - [Historical archives of Italian nephrology: Introduction of the artificial kidney
      in Italy].
AB  - In Italy the first attempts at haemodialysis, first in vitro and animals and then
      in humans, were carried out in the early 1950s by the surgeons Mario Battezzati e
      Carlo Taddei of Genoa with an artificial kidney of their own design. During the
      same years several other surgeons and urologists in Padua, Milan, Turin,
      Florence, Modena, Rome, Naples and Palermo designed their own artificial kidneys,
      which were used to treat anuric patients suffering from acute renal failure. The
      lively interest in artificial kidneys led, in 1954, to the organisation of a
      symposium on the subject. This was the first symposium of its kind not only in
      Italy but also at European level and was characterised by a wide discussion on
      all aspects associated with extracorporeal dialysis. In subsequent years the use
      of artificial kidneys continued to develop in several of the above-mentioned
      Italian centres, something that in the early 1960s led to the introduction of
      chronic haemodialysis. This paper shows how in Italy the use of artificial
      kidneys was characterised by intense experimental and clinical activity as well
      as original approaches to the many problems associated with the use of this
      technique.

PMID- 12508172
TI  - [Heparin-induced thrombocytopenia syndrome and thrombosis in patients undergoing
      periodic haemodialysis].
AB  - Heparin-induced thrombocytopenia (HIT) is the most important immunological drug
      reaction that patients face today. Being unfractionated heparin the standard
      anticoagulation used in haemodialysis, acute or chronic uremic patients starting
      haemodialysis are at risk of developing HIT. Through the accurate description of
      two patients, one with chronic and the other with acute uraemia, who developed
      this complication at the start of haemodialysis, we compare the distinct clinical
      problems of haemodialysis-related HIT with the general clinical features of HIT.
      We report the occurrence of repeated clotting of both dialysers and catheters, as
      well as thrombosis of the central veins where the catheters are placed and of the
      fistulas. We also report an accurate review of the literature on haemodialysis
      related HIT. We have observed that HIT seems to be particularly rare in
      haemodialysis patients. Since newly treated haemodialysis patients are at risk of
      developing HIT, and most of the studies were made on long-term chronic
      haemodialysis patients, we assume that the syndrome is poorly documented. Our own
      experience on 37 haemodialysis patients who developed HIT is reported by focusing
      on both the clinical presentation of HIT as well as the long-term follow up of
      the patients. We present some considerations on the treatment options of acute
      HIT in uremic patients as well as on the problem of heparin re-exposure
      subsequent to the HIT episode, a very prominent problem in chronic haemodialysis
      patient.

PMID- 12508173
TI  - [LithoRisk: A software for calculating and visualising nephrolithiasis risk
      profiles].
AB  - BACKGROUND: The pathogenesis of nephrolithiasis, based on the anomalies of the
      urinary environment, demands metabolic and physicochemical assessment for the
      medical management of patients. Standard metabolic protocols include the
      measurement of pertinent urine chemistry values and the calculation of the extent
      of saturation in stone-forming salts. However, patients are often given
      fragmentary and hard-to-consult reports and so this weakens the strength of the
      therapeutic recommendations. This paper introduces LithoRisk, a dedicated
      software which graphically represents risk profiles of stone formation, including
      the extent of saturation. METHODS: LithoRisk uses the results of 24-h urine
      chemistry values widely available in hospital laboratories, i.e., sodium,
      potassium, calcium, magnesium, ammonia, phosphate, sulphate, citrate, oxalate,
      chloride, pH and urine volume. Uric acid and cystine are optional. The relative
      supersaturation (beta), estimated according to our own ab initio calculation, is
      given in a scale whereby beta=1 is saturation, beta < 1 under - and beta > 1
      oversaturation. LithoRisk is available as a CD-ROM and can be loaded on Windows
      95/98/Millenium/XP. Colour or laser printers are suitable for printed records.
      RESULTS: LithoRisk is easily loaded on any PC by following video instructions.
      Once the loading of the program is completed a grey icon LithoRisk appears on the
      Desktop. The program can be opened by clicking twice on the icon. The patients
      data page first appears on the screen and is followed by the evaluation page for
      the input of variables. This generates the graph representing the diagnostic
      lithorisk profile, which is drawn as a line connecting different values,
      according to a specific scale and related to an arbitrary normal point. Normal
      values are shown as green lines, whereas abnormal ones are red. The beta values
      for calcium oxalate and phosphate, uric acid and cystine are instantaneously
      calculated and reported on the graph. CONCLUSIONS: LithoRisk produces a complete,
      unique and easy to understand report that includes all relevant parameters, it
      therefore expresses the overall risk of stone formation. It requires the results
      of chemistry tests done on the same 24-h urine collection, and carried out using
      suitable preservatives. If the tests for unusual parameters, i.e. sulphate and
      ammonia, are unavailable, one can use default values with minimal alterations on
      beta calculation. In spite of being arbitrary, the normal thresholds values are
      based on widely accepted literature data. The risk profile recognises the most
      relevant abnormalities and enables the establishment of individual targets aimed
      at reducing the propensity towards stone formation.

PMID- 12508174
TI  - Immunocytochemistry of serous effusion specimens: a comparison of ThinPrep vs
      cell block.
AB  - The ThinPrep Processor is gaining popularity in both gynecologic and
      nongynecologic cytologic samples, including effusion specimens. We compared
      immunocytochemical results on ThinPrep and cell-block preparations from the same
      effusion specimen with antibodies commonly used in effusion cytopathology.
      Samples from 17 reactive effusions and 79 effusions with metastatic
      adenocarcinomas were each prepared as monolayer ThinPreps and formalin-fixed,
      paraffin-embedded cell blocks. All slides were immunostained with antibodies
      against intermediate filaments (cytokeratins 8 and 18, and vimentin), cytoplasmic
      or membrane proteins (EMA, polyclonal CEA, B72.3, and BerEP4), and nuclear
      antigens (Ki67, PCNA, and p53), using the avidin-biotin procedure. ThinPrep and
      cell-block slides were stained simultaneously, using identical protocols. Both
      preparations showed similar results with respect to frequency of positivity,
      intensity, and distribution of stain for all nonnuclear markers tested. However,
      for the three nuclear markers Ki67, PCNA, and p53, the frequency and intensity of
      reaction with ThinPrep were significantly lower than with the cell-block
      preparation, particularly in malignant effusions. These findings suggest that
      immunocytochemical results obtained with ThinPrep match those of cell block for
      most markers tested. However, cell-block preparation are superior to ThinPrep for
      nuclear markers (Ki67, PCNA, and p53).

PMID- 12508175
TI  - Percutaneous image-guided fine-needle aspiration of peritoneal lesions.
AB  - Fine-needle aspiration (FNA) is a widely accepted technique for the initial
      tissue diagnosis of a variety of lesions arising within retroperitoneal and
      intraabdominal viscera. Fear of complications secondary to perforation of the
      bowel wall has limited the use of FNA in the diagnosis of gastrointestinal and
      peritoneal masses. A variety of primary and secondary neoplasms involving the
      peritoneum may present as multiple nodules, as masses, or as diffuse involvement
      of the peritoneum. When these lesions are associated with mass lesions or areas
      of significant peritoneal thickening, they become amenable to percutaneous image
      guided FNA. We report on our experience with a series of 23 peritoneal lesions
      investigated by FNA for which subsequent histologic confirmation was available in
      19, along with an additional 4 cases without histologic confirmation. One to four
      passes were made into each lesion, and immediate assessment for adequacy was
      performed by a cytopathologist in all cases. All 17 cases with a specific
      cytologic diagnosis and histologic confirmation represented either primary or
      metastatic neoplasms (5 gastrointestinal stromal tumors, 4 metastatic melanomas,
      2 mesotheliomas, 1 lymphoma, 1 example of Kaposi's sarcoma, 1 serous papillary
      carcinoma of ovarian origin, 1 mucinous adenocarcinoma of ovarian origin, 1
      intraabdominal desmoplastic small-cell tumor, and 1 solitary fibrous tumor of the
      peritoneum). In an additional 4 cases, the aspirates were judged as insufficient
      for diagnosis, with the smears containing only blood and benign mesothelial cells
      and/or inflammatory cell elements. These four smears were associated with both
      neoplastic and nonneoplastic lesions. Surgical confirmation was obtained in only
      2 of these cases (1 metastatic melanoma and 1 example of omental and peritoneal
      involvement by an ovarian adenocarcinoma). Two cases without histologic
      confirmation were associated with clinically confirmed metastases. In our series,
      no acute or chronic postprocedural complications were identified, indicating that
      FNA in this setting is a safe technique. Accurate cytologic diagnosis was
      achieved in 74% of cases. The overall insufficiency rate was 26%.

PMID- 12508176
TI  - Diagnosis and grading of chondrosarcomas on FNA biopsy material.
AB  - A consecutive series of 47 chondrosarcomas was reviewed to identify the most
      useful criteria for cytological diagnosis, and grading in comparison to histology
      grade. This series includes 39 evaluable cases, including 2 patients with
      Ollier's disease and 2 with extraskeletal chondrosarcomas. Eight cases were
      excluded because of lack of histologic confirmation (3). nondiagnostic cytology
      (4). and one inconclusive histologic diagnosis. The cytologic diagnosis of these
      tumors was based on the identification of chondrocytes and a chondromyxoid
      stroma. The chondrocytes often showed double nuclei (34/39) and macronucleoli
      (20/39). Nuclear atypia in terms of distinct variation in size was less common
      (16/39). Cytoplasmic granules and vacuoles were often seen (34/39 and 29/39,
      respectively). In smears, chondroid fragments and a chondromyxoid background were
      seen in a majority of cases (36/39 and 30/39, respectively). By grade,
      concordance with histology was present in 4/7 grade I tumors, 26/29 grades II
      III, and 5/5 grade IV, respectively.

PMID- 12508177
TI  - Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma in
      cervical lymph nodes: comparison with metastatic squamous-cell carcinoma, and
      Hodgkin's and non-Hodgkin's lymphoma.
AB  - Our objective was to study the cytomorphological features of metastatic
      nasopharyngeal carcinoma (NPC) as compared to squamous-cell carcinoma (SCC) of
      nonnasopharyngeal origin, Hodgkin's lymphoma (HL), and non-Hodgkin's (NHL)
      lymphoma in the neck lymph nodes. The aim of this study was to find simple
      cytological criteria using routine stains that can help in differentiating
      between these entities. All fine-needle aspiration (FNA) smears of metastatic
      NPC, SCC, HL, and NHL from neck nodes available in our files were included in
      this study. Nodal disease was the first clinical manifestation in all cases of
      NPC, and all the lesions were of the nonkeratinizing type. The cytomorphological
      features of metastatic NPC, SCC, HL, and NHL have been described. Metastatic NPC
      and HL had a similar reactive lymphoid background, with eosinophils, plasma
      cells, and sometimes epithelioid-cell granulomas. The bizarre cells of NPC showed
      some resemblance to Reed-Sternberg cells of HL. However, the latter can be
      distinguished from the former on the basis of bulky, pale gray, vacuolated
      cytoplasm and vesicular nuclei with sharply demarcated prominent macronucleoli.
      In NPC, the neoplastic cells form distinct aggregates contrasting with the normal
      lymphoid cells in the background, which was different from the monotonous
      dispersed population of cells in NHL. Moreover, bizarre cells, prominent
      nucleoli, and the presence of plasma cells, eosinophils, and granulomas were not
      common features of NHL. The smears of metastatic SCC revealed keratinized
      malignant cells in all cases, while eosinophils and plasma cells were absent in
      the background. Plasma cells were seen intimately related to tumor cells in all
      cases of NPC. In conclusion, metastatic NPC can be differentiated from metastatic
      SCC of nonnasopharyngeal origin, HL, and NHL on the basis of simple nuclear and
      cytoplasmic features of malignant cells and their background. The presence of
      plasma cells intermingling with tumor-cell clusters is a good indicator of
      nasopharyngeal origin. On the other hand, a nasopharyngeal origin is unlikely in
      the presence of keratinized malignant cells.

PMID- 12508178
TI  - False-positive squamous cell carcinoma in cervical smears: cytologic-histologic
      correlation in 19 cases.
AB  - Cytologic features of squamous intraepithelial lesions (SIL) can mimic those of
      invasive squamous-cell carcinoma. We compare and correlate the cytological
      findings of 19 false-positive squamous-cell carcinomas with follow-up cone
      biopsies or hysterectomy specimens to define which type of dysplasia is more
      prone to diagnostic errors on cervical Papanicolaou (Pap) smears. Out of 128
      patients diagnosed with invasive squamous-cell carcinoma from 1994-2000, 19
      (14.8%) with follow-up cone biopsies or hysterectomy specimens were false
      positive cases, showing only cervical intraepithelial neoplasia (CIN). We
      reviewed tissue sections from these 19 cases of CIN for cytologic features of
      squamous-cell carcinoma, such as markedly pleomorphic and/or dysplastic squamous
      cells, necrosis, and nucleoli. Twelve of 19 patients (63%) were menopausal. The
      mean age was 50.5 yr. On review of cervical smears, 18 cases qualified for the
      cytologic diagnosis of squamous-cell carcinoma, keratinizing type, and one case
      qualified for squamous-cell carcinoma, nonkeratinizing type. Pleomorphic and/or
      keratinizing dysplasia was found in 15 out of 19 patients (79%), necrosis within
      superficial endocervical glands in 9 out of 19 patients (47%), and conspicuous
      nucleoli in 12 out of 19 patients (63%). One or more of these changes were seen
      in all but 2 patients (89%). Endocervical gland involvement was present and
      extensive in 18 of the 19 cases (94%). The mean age was older than expected for
      SIL (50.5 vs. a reported 40), and matched the mean age found in patients with
      invasive squamous-cell carcinoma. Pleomorphic and/or keratinizing dysplasia
      involving endocervical glands may exhibit the cytologic features of squamous-cell
      carcinoma on cervical Pap smears.

PMID- 12508179
TI  - Cytologic-histologic correlation of nongynecologic cytopathology cases:
      separation of determinate from indeterminate cytologic diagnoses for analysis and
      monitoring of laboratory performance.
AB  - Much of the literature on the quality-assurance aspect of cytologic-histologic
      correlation (CHC) has focused on gynecologic cytology. For nongynecologic
      cytopathology, the process is complicated by the use of determinate (positive for
      malignant cells, negative for malignant cells) and indeterminate (atypical,
      suspicious, or follicular lesion) diagnostic categories. Here, we illustrate our
      routine methodology for analyzing CHC data on nongynecologic cytopathology cases
      by separating determinate from indeterminate cases. A focused list of determinate
      and indeterminate cytopathology cases with surgical pathology correlation is
      generated each week. The determinate cases are ascertained as true positive (TP),
      true negative (TN), false positive (FP), or false negative (TN). The discrepant
      cases (FP and FN) are investigated to determine the cause (sampling,
      interpretation, or screening). For indeterminate cases, the surgical pathology
      outcome (benign, malignant) and suitability of the cytopathology category
      utilized are reviewed. For the focused period of 4 mo, sensitivity was 70% and
      specificity was 100%. The most common reason for false-negative diagnoses was a
      sampling problem in the cytologic specimen; there were no false-positive
      diagnoses. Malignant outcomes for follicular lesion, atypical, and suspicious
      diagnoses were 29%, 40%, and 76%, respectively. Data derived from regularly
      performed CHC are useful in reviewing the diagnostic performance of the
      laboratory.

PMID- 12508180
TI  - Follicular thyroid lesions coexisting with Hashimoto's thyroiditis: incidence and
      possible sources of diagnostic errors.
AB  - Our objectives were to study the types and incidence of thyroid follicular
      lesions coexisting with Hashimoto's thyroiditis (HT), the pitfalls in their
      cytodiagnosis, and the effect on management. All cases of HT diagnosed by fine
      needle aspiration (FNA) and/or histology over a 7-yr period were retrospectively
      studied. HT coexisted with follicular adenoma (FA) in 6 cases, follicular variant
      of papillary carcinoma (FVPC) in 1 case, and goitrous nodule (GN) in 2 cases. The
      overall incidence rates of thyroid neoplasm and goitrous nodules coexistent with
      HT were 15% and 3.5%, respectively. A preoperative FNA diagnosis was available in
      10 histologically proven cases of HT. A false-positive diagnosis of follicular
      neoplasm (FN) that led to unnecessary thyroidectomies was given in 3 cases. In 2
      of these, the cytological diagnosis was HT with the possibility of coexisting FN,
      and in the third case, the cytological finding of HT was misinterpreted as FN.
      The main causes of these diagnostic pitfalls were the presence of hyperplastic
      follicular cells with nuclear pleomorphism, a paucity of lymphoid cells in burned
      out HT, and lack of ones exposure. Nuclear pleomorphism was observed in none of
      the follicular adenomas. FNA diagnosed accurately the coexisting lesions in 6
      cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA
      diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a
      coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by
      85.7%, with no false-negative results. Indeed, aspiration on and around the
      thyroid nodule helps in sampling HT. However, HT may dominate the smear and
      obscure neoplasia. This can be avoided if the procedure is performed by the
      pathologist and the aspiration is done on the nodule only. The overlapping
      cytological features of FN and HT were the main causes of false-positive results.
      This can be reduced by avoiding the diagnosis of FN in the presence of follicular
      cell pleomorphism and/or moderate to excessive numbers of lymphoid cells,
      provided proper aspiration technique is maintained.

PMID- 12508181
TI  - Aspiration cytology of cystic carcinoma of the breast.
AB  - Cystic carcinomas of the breast are rarely encountered in fine-needle aspiration
      (FNA) biopsies. The most common entities comprise intracystic papillary
      adenocarcinoma, ductal adenocarcinoma with cystic degeneration including comedo
      forms of ductal adenocarcinoma in situ, medullary carcinoma, squamous carcinoma,
      and cystic hypersecretory ductal adenocarcinoma. The cytologic diagnosis is often
      hampered by sparse cellularity, abundant obscuring blood, necrotic debris, and
      degenerative changes in diagnostic cells. We report on the cytologic features of
      10 cases of cystic carcinoma, including 12 FNA biopsies with radiologic and
      surgical correlation. The original cytologic diagnoses for these cases were:
      benign (2 cases), atypical (2 cases), suspicious (3 cases), and positive for
      malignant cells (3 cases). On repeat FNA, one benign case and one atypical case
      were reclassified, respectively, as atypical and suspicious for carcinoma. The
      follow-up diagnoses were 5 intracystic papillary adenocarcinomas and 5 cystic
      ductal adenocarcinomas. Despite 2 false-negative cases, all cases were adequately
      managed. Correlation with clinical and radiologic findings and direct sampling of
      any solid component of these cystic neoplasms are crucial in diagnosis and
      management.

PMID- 12508182
TI  - Quick aspiration cytology for thyroid nodules by modified Ultrafast Papanicolaou
      staining.
AB  - Quick cytologic diagnosis by Ultrafast Papanicolaou stain (Ultrafast stain) is
      useful in various neoplastic diseases; however, it has a significant drawback in
      that the ground-glass appearance of nuclei is a preparation artifact in some
      specimens from thyroid aspirations. To eliminate this artifact, the nucleus was
      stained with Gill-5 Hematoxylin (modified Ultrafast stain) rather than with
      Richard-Allan Hematoxylin 2 in Ultrafast stain. The applicability of this
      modified Ultrafast stain for quick diagnosis of thyroid diseases was
      investigated. Two specimens from each of 251 thyroid aspirations (122 malignant
      and 131 benign) were prepared using the modified Ultrafast stain and the standard
      Papanicolaou stain. The sensitivities of cytologic diagnosis in specimens stained
      by the standard Papanicolaou method and the modified Ultrafast method were 95.0%
      and 93.3%, respectively, and the specificities were 99.2% and 97.7%,
      respectively. The modified Ultrafast stain is a reliable procedure for quick
      diagnosis in thyroid aspiration cytology.

PMID- 12508183
TI  - Fine-needle aspiration cytology of metastatic carcinoid tumor: report of a case
      and review of the literature.
AB  - While carcinoid tumor is a relatively common neoplasm in surgical pathology, fine
      needle aspiration (FNA) cytology as a method of primary diagnosis has only been
      reported in the literature a few times. We report on the case of a 42-yr-old
      female with multiple large metastatic tumor deposits in her liver, pelvic
      adnexae, bones, and lungs, with an unknown primary. FNA was performed on one of
      the liver masses, and was diagnosed using routine histochemical and
      immunohistochemical stains as carcinoid tumor. No follow-up tissue diagnosis has
      been obtained. However, the patient is still alive with her tumor 1 yr later.
      Fine-needle aspiration cytology can be a useful and safe tool in the diagnosis of
      metastatic carcinoid tumors, avoiding the need for surgery which would not
      otherwise be indicated for treatment.

PMID- 12508184
TI  - Tumor imprint cytology of sclerosing stromal tumor of the ovary.
AB  - Over 90 cases of sclerosing stromal tumor of the ovary (SST) have been reported
      in the English-language literature, but these authors did not mention the
      cytologic examination of SST. In 2 patients with SST, we were able to collect
      specimens for tumor imprint cytology. The number of cells in the specimens was
      extremely small. Two types of benign cells were observed against a clean
      background, comprising cells with round nuclei surrounded by abundant cytoplasm
      and cells with spindle-shaped or oval nuclei that had scanty cytoplasm. Our
      present findings suggest that intraoperative imprint cytology was able to rule
      out cancer. Considering that SST most commonly occurs in young women requiring
      conservative treatment, imprint cytology seems to have a potential diagnostic
      significance.

PMID- 12508185
TI  - Perineal nodule due to enterobiasis: an aspiration cytologic diagnosis.
AB  - Subcutaneous swelling due to Enterobious vermicularis infection is rare. Their
      presence in perineal subcutaneous tissue is unusual and a clinical curiosity. A
      case of subcutaneous nodule in the perineum due to E. vermicularis infection
      diagnosed on fine-needle aspiration is described. Tissue reaction was
      granulomatous with neutrophils and eosinophils. Lack of familiarity with the
      morphology of parasites or its eggs, degeneration, and inadequate sampling may
      make the diagnosis difficult. This case report provides the morphologic clues to
      cytopathologists toward rendering a diagnosis and alerts them to the possibility
      of parasitic infection in unusual locations.

PMID- 12508186
TI  - Cytopathology in Spain.

PMID- 12508187
TI  - Outcome of access site in patients treated with platelet glycoprotein IIb/IIIa
      inhibitors in the era of closure devices.
AB  - The most consistent procedural predictor of vascular access site complications
      thus far has been the intensity and duration of anticoagulant therapy during and
      after percutaneous coronary interventions (PCI). Several devices have been
      developed to aid in the closure of the femoral arteriotomy. This report describes
      the clinical outcome of unsuccessful deployment of femoral closure devices in a
      cohort of 285 consecutive patients who underwent PCI and were treated with
      platelet glycoprotein (GP) IIb/IIIa inhibitors. Manual femoral artery compression
      was used in 123 patients, Perclose in 123 patients, and AngioSeal in 39 patients.
      Successful homeostasis was achieved in 98.4% of patients who received manual
      compression, in 91.9% of the Perclose-sealed arteriotomy, and in 84.6% of
      patients who received the AngioSeal closure device (P = 0.004). The incidence of
      vascular complications after successful deployment was 9%. Patients not achieving
      hemostasis with closure device or 1 degrees manual compression developed
      complications in the majority of cases (> 80%; P < 0.05). By multivariate
      analysis (with adjustment for baseline differences), the use of AngioSeal closure
      device was found to be an independent risk factors leading to primary deployment
      failure and all access site complications (OR 2.97; 95% CI 1.5-6.0; P = 0.006).
      In summary, failed hemostasis by artery closure devices in patients undergoing
      PCI who are treated with GP IIb/IIIa inhibitors is associated with significant
      vascular complications. AngioSeal may be associated with a higher failure rate,
      while manual compression and Perclose seem to be more effective with a lower
      complication rate.

PMID- 12508188
TI  - News you can't use much longer: the low-volume retrospective closure device
      comparison.

PMID- 12508189
TI  - Coronary angiography in the fully anticoagulated patient: the transradial route
      is successful and safe.
AB  - The radial approach to coronary angiography is intuitively attractive for fully
      anticoagulated patients (INR > 2) but no data exist concerning efficacy or safety
      of this procedure. The consensus view is that the femoral approach is
      contraindicated in fully anticoagulated patients, and though some operators
      undertake femoral catheterization in such patients and use closure devices, there
      are no data to suggest that it is safe to do so. At our institution, the radial
      approach for coronary angiography is reserved for patients in whom there is a
      relative contraindication to the femoral route. We have undertaken over 600
      radial coronary angiograms in such patients since 1996, 66 of whom underwent
      transradial catheterization specifically because of anticoagulation status (INR >
      2). Thirty-eight patients (58%) were male, average age 67 +/- 11 years. All 66
      patients had an INR > 2 but < 4.5. The approach was left radial in 26 (39%),
      right radial in the remainder; sheath size was 4 Fr in 4 (6%), 5 Fr in 13 (20%),
      and 6 Fr in 49 (74%). Seven operators in total were involved, though two
      operators undertook the majority of cases (47; 71%). Success rate was 97%, with
      no failure of access, and only one minor postprocedural hemorrhage. Failures were
      due to radial artery atherosclerosis (1) and subclavian tortuosity (1). The
      radial approach to coronary angiography is safe and to be recommended in the
      fully anticoagulated patient.

PMID- 12508190
TI  - Treatment of coronary stent thrombosis with rheolytic thrombectomy: results from
      a multicenter experience.
AB  - The objective of this study was to assess the feasibility, efficacy, and safety
      of rheolytic thrombectomy (RT) for treatment of coronary stent thrombosis. Stent
      thrombosis is an infrequent but potentially devastating complication.
      Conventional treatment with balloon angioplasty and/or thrombolysis has yielded
      suboptimal results. RT was used to treat 18 patients (mean age, 62 +/- 8 years;
      72% male) with in-stent thrombosis (mean time to stent thrombosis, 2.4 +/- 1.8
      days). Device success, procedure success, in-hospital and 30-day major
      cardiovascular events (MACE) were assessed in the hospital and at 30 days. Device
      success was obtained in 94% and procedure success was achieved in 100% of
      patients. Following RT, 11 patients underwent balloon angioplasty and 7 patients
      received additional stents. TIMI 3 coronary flow was obtained in 94.4% and all
      (100%) patients achieved either TIMI 2 or 3 coronary flow. The angiographic
      thrombus area decreased from 113.7 +/- 79 to 5.5 +/- 5.7 mm(2) after RT, and to
      0.9 +/- 2.1 mm(2) (P < 0.001) after final treatment. Procedural complications
      were limited to transient no-reflow in five patients. Only one patient evolved a
      Q-wave MI. At 30 days of follow-up, no patients suffered death, emergent bypass
      surgery, or stroke. Our data suggest that the adjunctive use of rheolytic
      thrombectomy offers improved outcomes compared to prior results of intervention
      after coronary stent thrombosis and should be strongly considered as a treatment
      option for this complication.

PMID- 12508191
TI  - Late stent thrombosis: is AngioJet the preferred revascularization technique?

PMID- 12508192
TI  - Comparison of outcomes in women and men treated with coronary stent implantation.
AB  - Worse outcomes have been observed in women after PTCA. The present study was
      undertaken to compare clinical and angiographic results of coronary stenting
      among women and men. We retrospectively analyzed acute and 6-month results in a
      consecutive series of 940 men and 160 women undergoing coronary stent
      implantation between May 1992 and January 1998. Women were older (63 vs. 57
      years; P = 0.001), more often hypertensive (46.9% vs. 31.4%; P < 0.001) and
      diabetic (13.2% vs. 8.3%; P = 0.05), and less often smokers than men (32.5% vs.
      70.5%; P < 0.001). A previous history of Q-wave MI was less frequently present in
      women (28.2% vs. 40.2%; P = 0.003) who more often underwent coronary
      revascularization because of unstable angina (37.5% vs. 27.1%; P = 0.027). No
      difference was observed in coronary artery disease extension, lesion complexity,
      and stented vessel between the sexes. Bailout stenting was more frequently needed
      in women (28% vs. 17.8%; P = 0.001). No difference was observed in the number of
      stent implanted per vessel and per patient and average maximal inflation pressure
      used for stent postdilation. However, a smaller final balloon size was used in
      women. Procedural and clinical success was achieved in 94.4% and 92.5% of women
      and 96.7% and 94.5% of men (P = NS), respectively, without differences regarding
      in-hospital major adverse cardiac events. Bleeding complications occurred more
      often in women when anticoagulation was used (OR = 2.87; 95% CI = 1.38-5.74). At
      6-month clinical follow-up, TLR was similar between the sexes and event-free
      survival was 75.5% in women and 81.5% in men (P = NS). Angiographic follow-up,
      performed in 71% of the patients, showed that restenosis was 64% higher in women
      (OR = 1.64; 95% CI = 1.02-2.61). Despite older age, higher incidence of
      comorbidities, and more unstable presentation, women treated with coronary
      stenting showed acute and mid-term clinical results similar to those observed in
      men. However, they were significantly more likely to develop angiographic
      restenosis.

PMID- 12508193
TI  - Change of the mechanical properties of two different balloon catheters with
      increasing numbers of cycles of resterilization.
AB  - An increasing number of centers are reusing PTCA catheters even though
      manufacturers warrant single use only. This prospective bench laboratory trial
      addresses the quality of PTCA balloon catheters after up to three resterilization
      cycles in order to determine whether a larger trial is warranted to discern
      whether catheters should be reused. Forty PTCA catheters from two different
      manufacturers (nominal diameters 1.5 and 3.0 mm) were taken from the shelf. An
      independent institute tested mechanical properties such as burst pressure,
      nominal diameter, crossing profile, and balloon surface. The crossing profile
      increased by 22.5%-39.2% with no additional deterioration after repeated
      sterilizations. The nominal diameter either increased or decreased by a maximum
      of 47%. In all 1.5 mm balloons, the burst pressure remained above the
      manufacturers' values, whereas in the 3.0 mm balloons, the value dropped below
      the rated burst pressure in 40%-50% of the trials. In conclusion, in both
      catheter types analyzed, reuse was associated with a considerably worse quality,
      which puts in question their routine clinical use.

PMID- 12508194
TI  - A new dedicated stent and delivery system for the treatment of bifurcation
      lesions: preliminary experience.
AB  - We report the first clinical experience in eight patients with a new stent and
      delivery system specifically designed for the treatment of bifurcational lesions.
      The device (AST SLK-View system) consists of a premounted stent and a delivery
      system. The stent has a side aperture, which orients toward the ostium of the
      side branch. The system allows deployment of the stent while the access to both
      main and side branches is maintained by two wires. We evaluated this system in
      nine bifurcations. The location of bifurcations was left descending
      artery/diagonal branch in four lesions, left circumflex/obtuse marginal branch in
      three lesions, and postero-lateral branch/posterior descending artery in two
      lesions. Predilation was performed in six lesions of the main branches and in
      five lesions of the side branches. The stent was effectively delivered to all
      bifurcations except for one, in which the target lesion was located at a distal
      segment and the device could not be delivered. Following stent implantation in
      the main branch, two lesions at the side branches were treated by stent, while
      the other lesions were treated by balloon angioplasty without difficulty. Final
      kissing balloon was performed in four bifurcation lesions. No adverse event was
      observed during 1 month of clinical follow-up. Treatment of bifurcation lesions
      with this new dedicated device appears to be feasible. This new device may
      introduce a new approach for the treatment of coronary bifurcation lesions.

PMID- 12508195
TI  - Coronary flow reserve correlates left ventricular diastolic dysfunction in
      patients with dilated cardiomyopathy.
AB  - The relationship between altered coronary circulation and left ventricular (LV)
      function in dilated cardiomyopathy (DCM) remains unclear. We used the Doppler
      guidewire and transthoracic echo Doppler in 24 DCM patients to investigate the
      relationship between coronary flow reserve (CFR) and LV systolic/diastolic
      function, trying to predict diastolic dysfunction and evaluate DCM severity with
      CFR. CFR correlated better with the deceleration time (DT) of the E-wave and the
      ratio of E-wave peak value to that of the A-wave (E/A) than with LV ejection
      fraction (EF). The optimal CFR cutoff value for predicting the restrictive
      pattern of transmitral flow velocity (DT = 120 msec) was 2.6 (sensitivity 91%,
      specificity 100%). Dividing patients into two groups around the CFR = 2.6 cutoff,
      differences in DT and E/A between groups were more prominent than those for EF.
      CFR correlates better with LV diastolic than systolic function and may be useful
      for predicting diastolic dysfunction in DCM patients.

PMID- 12508196
TI  - Direct coronary stenting without balloon predilation of lesions requiring long
      stents: immediate and 6-month results of a multicenter prospective registry.
AB  - To assess the outcomes of direct coronary stenting (DS) using long stents and
      examine predictive factors of DS failure, this prospective multicenter registry
      included 128 consecutive patients who underwent the implantation of stents >or=
      18 mm in length without balloon predilation for de novo coronary artery stenoses.
      Mean lesion and stent lengths were 20.7 +/- 5.4 and 21.4 +/- 3.8 mm,
      respectively. Rates of DS success, lesion success, and primary success were 82%,
      99%, and 97.7%, respectively. At 6 months, rates of MACE and TVR were 12.5% and
      6.3%, respectively. In multivariate analysis, factors predictive of DS failure
      vs. DS success were presence of calcifications (78% vs. 45%; P = 0.004) and
      reference vessel diameter (2.77 +/- 0.4 vs. 3.13 +/- 0.42 mm; P = 0.0002). DS of
      complex lesions with stents >or= 18 mm in length was performed safely and with a
      high success rate. This strategy was less successful in the treatment of small
      vessels and in presence of calcifications.

PMID- 12508197
TI  - Continuous veno-venous hemofiltration for the treatment of contrast-induced acute
      renal failure after percutaneous coronary interventions.
AB  - Acute renal failure (ARF) requiring hemodialysis after percutaneous coronary
      interventions (PCI) is a serious complication with poor prognosis. Hemodialysis
      induced hypotension may have deleterious cardiovascular effects, especially in
      high-risk patients. Ultrafiltrate removal and simultaneous fluid replacement with
      a solution similar to plasma for high-volume controlled hydration can be obtained
      with hemodynamic stability by continuous veno-venous hemofiltration (CVVH). We
      prospectively assessed the safety and effectiveness of percutaneous CVVH (Y
      shaped double-lumen catheter, circuit originating from and terminating in the
      femoral vein) in 33 consecutive patients (23 men and 10 women; mean age, 69 +/- 9
      years) who, after PCI, developed oligo-anuric ARF, associated in 20 of them with
      congestive heart failure. All patients received a concomitant infusion of
      furosemide (500-1000 mg/day) and dopamine (2 microg/kg/min). During CVVH, the
      average fluid volume replacement and body fluid net reduction were 1000 +/- 247
      and 75 +/- 48 ml/hr, respectively. Treatment with CVVH continued for 4.7 +/- 2.7
      days and corrected fluid overload in all cases. No patient experienced systemic
      hypotension or hypovolemia. Diuresis recovered in 32 (97%) patients, who showed a
      parallel improvement of renal function parameters. One patient required chronic
      dialysis. In-hospital and 1-year mortality was 9.1% and 27.3%, respectively. In
      conclusion, our data indicate that CVVH is a safe and effective therapy of
      radiocontrast-induced ARF following PCI. It temporarily replaces renal function
      without deleterious cardiovascular effects, allowing the kidney to recover from
      the nephrotoxic injury. However, despite promising early results, large
      randomized trials are required to define the role of CVVH in ARF after PCI.

PMID- 12508198
TI  - Combination platelet glycoprotein IIb/IIIa receptor and lepirudin administration
      during percutaneous coronary intervention in patients with heparin-induced
      thrombocytopenia.
AB  - We evaluated a combination therapy using glycoprotein IIb/IIIa receptor
      antagonism and direct thrombin inhibition in nine patients with heparin-induced
      thrombocytopenia (HIT) undergoing 10 percutaneous coronary interventions (PCIs).
      In selected patients with HIT, the combination of a direct thrombin inhibitor,
      lepirudin, and abciximab, tirofiban, or eptifibatide appears to be a safe and
      effective anticoagulation strategy for PCI.

PMID- 12508199
TI  - Coronary abscess: a complication of stenting.
AB  - We report the case of a 72-year-old male who underwent primary angioplasty for an
      acute myocardial infarction and developed a coronary stent infection with
      Staphylococcus aureus. The patient was treated with a prolonged course of IV
      antibiotics and underwent debridement and partial stent extraction successfully.

PMID- 12508200
TI  - "Fog (and infection) creeps in on little cat feet".

PMID- 12508201
TI  - Acute profound thrombocytopenia after use of eptifibatide for coronary stenting.
AB  - This is a case report of a patient who developed profound thrombocytopenia during
      treatment with eptifibatide after PCI of the mid right coronary artery.

PMID- 12508202
TI  - Eptifibatide-induced acute profound thrombocytopenia presenting as refractory
      hypotension.
AB  - A 61-year-old woman presented with acute coronary syndrome and was given heparin
      and eptifibatide in conjunction with coronary angioplasty. Shortly thereafter she
      became profoundly thrombocytopenic (platelets 2.0 x 10(9)/L) and developed severe
      refractory hypotension. Heparin-induced antibodies were not detected, but the
      patient developed strong eptifibatide-dependent antibodies specific for platelets
      that appear to explain both the thrombocytopenia and the hypotensive episode.

PMID- 12508203
TI  - Subacute stent thrombosis associated with a heparin-coated stent and heparin
      induced thrombocytopenia.
AB  - Subacute stent thrombosis occurred in a patient 34 days after receiving a heparin
      coated (HC) stent. The patient developed heparin-induced thrombocytopenia and
      diffuse thrombosis after the stent was placed. This raises the concern that
      patients who develop heparin-associated antibodies in the context of a recently
      placed HC stent may have an increased risk for subacute stent thrombosis.

PMID- 12508204
TI  - Heparin-coated stent and heparin-induced thrombocytopenia: true, true, and
      conceivably related.

PMID- 12508205
TI  - Carotid brachytherapy for in-stent restenosis.
AB  - Carotid stenting has emerged as an alternative revascularization modality to
      endarterectomy for the treatment of carotid artery disease. Restenosis of a
      carotid stent may be occasionally seen. Our experience in intravascular radiation
      therapy for coronary restenosis has provided us the opportunity to explore this
      treatment strategy for carotid restenosis. We report our initial experience with
      brachytherapy for the treatment of restenosis after carotid stenting.

PMID- 12508206
TI  - Treatment of carotid stent restenosis.

PMID- 12508207
TI  - Percutaneous bare Z-stent implantation as an alternative to surgery for acute
      aortic dissection with visceral ischemia.
AB  - We describe a case of Stanford type B acute aortic dissection causing visceral
      ischemia. An aortogram showed an hourglass-like narrowing of the true lumen at
      the diaphragm with a 60 mm Hg pressure gradient. Placement of a self-expanding
      metallic Z-stent under intravascular ultrasound guidance restored blood flow to
      the viscera.

PMID- 12508208
TI  - Endovascular treatment of aortic dissections.

PMID- 12508209
TI  - Endovascular treatment of aortic rupture during angioplasty for aortic in-stent
      restenosis in aortoarteritis.
AB  - Aortic rupture during balloon angioplasty for in-stent restenosis without
      attempting to overexpand it is a rarity. We report a case of a young woman with
      aortoarteritis who had aortic rupture during angioplasty for in-stent restenosis.
      The balloon used was of the same diameter as the previously implanted stent and
      was completely within the stent during inflation. The disruption was successfully
      treated by percutaneous placement of a self-expandable endovascular stent graft.

PMID- 12508210
TI  - Transcatheter Amplatzer duct occluder closure of direct right pulmonary to left
      atrium communication.
AB  - Although rare, a congenital direct communication between pulmonary artery and
      left atrium can present a paradoxical embolism in adults. In our case, diagnosis
      was first made on contrast transcranial Doppler with Valsalva maneuver and
      subsequently confirmed by intracardiac echocardiography and selective pulmonary
      angiography. Successful catheter-based closure using Amplatzer duct occluder
      device resulted in definitive exclusion of the source of paradoxical embolism.

PMID- 12508211
TI  - Cardiac perforation following transcatheter PFO closure.
AB  - From December 1998 to August 2001, transcatheter closure of patent foramen ovale
      (PFO) with an Amplatzer PFO occluder has been successfully performed in our
      center in 102 patients without severe complications. We are reporting the first
      known case of cardiac perforation by an Amplatzer PFO occluder.

PMID- 12508212
TI  - Transcatheter occlusion of the patent foramen ovale: a long strange trip
      revisited.

PMID- 12508213
TI  - Longitudinal stent fracture 11 months after implantation in the left pulmonary
      artery and successful management by a stent-in-stent maneuver.
AB  - Fracture of a 12 mm Palmaz stent after implantation in the left pulmonary artery
      for palliation of postoperative stenosis in a 9-year-old child is described.
      Successful management by implantation of a second Palmaz stent revealed immediate
      stabilization and no signs of significant restenosis during 1-year follow-up.

PMID- 12508214
TI  - Right coronary arteriography: experience with standard-torque and limited-torque
      techniques in children and young adults.
AB  - Coronary spasm and intimal injury may occur during selective right coronary
      arteriography. The safety and efficacy of right coronary arteriography in
      children and young adults were retrospectively reviewed for this report. Right
      coronary arteriography was performed in 200 patients. A standard-torque technique
      was used in 150 patients, a limited-torque technique was used with a reshaped
      left coronary catheter in 53 patients. The standard-torque technique was
      associated with proximal coronary spasm in nine patients, nonsustained
      ventricular tachycardia in one patient, and ST segment changes in one patient.
      The limited-torque technique was associated with no complications. The standard
      torque technique was effective in one patient when the limited-torque technique
      failed to define distal coronary branches clearly. The limited-torque technique
      was effective in nine patients when the right coronary artery could not be
      engaged while attempting the standard-torque technique. In conclusion, right
      coronary arteriography may be performed in a safe and potentially more effective
      manner using a new catheter design and a limited-torque technique.

PMID- 12508215
TI  - Cardiac troponin I is increased after interventional closure of atrial septal
      defects.
AB  - This study was designed to assess possible myocardial injury caused by
      interventional closure of atrial septal defects (ASDs) compared to diagnostic
      catheterization by measuring cardiac troponin I (cTn-I). Forty patients were
      enrolled; in 33 ASDs were successfully closed, while in 7 a diagnostic balloon
      sizing of the defect was performed only. Total cTn-I increased significantly from
      0.1 to 1.9 microg/l at the end of the intervention and 2.23 at 4 hr and decreased
      to 1.35 at 15 hr. No significant increase could be detected in patients with
      diagnostic balloon sizing only or of CK/CK-MB levels either. Following
      interventional closure of ASDs with Amplatzer septum/PFO occluders, increased cTn
      I levels for several hours indicate some transient, reversible myocardial
      membrane instability due to the device. Discrimination of ventricular myocardial
      infarction might be possible by estimating less sensitive CK and CK-MB levels
      only.

PMID- 12508216
TI  - Transcatheter occlusion of ruptured sinus of valsalva aneurysm: innovative use of
      available technology.
AB  - A 9-year-old boy was found to have ruptured sinus of Valsalva aneurysm (RSVA) and
      aortic coarctation. Following relief of aortic coarctation by balloon
      angioplasty, transcatheter coil occlusion of the RSVA was performed successfully
      under transesophageal echocardiographic and fluoroscopic monitoring; bioptome
      assisted delivery of 0.052" Gianturco coil was undertaken via a 7 Fr sheath
      stabilized by an 0.035" guidewire passing through the RSVA and the sheath. This
      report details the technique of occlusion.

PMID- 12508217
TI  - Ruptured sinus of valsalva aneurysm: management options.

PMID- 12508218
TI  - Interventional cardiology manpower needs: how many of us are there? How many
      should there be? How many will we need in the future?

PMID- 12508219
TI  - Pronephric duct extension in amphibian embryos: migration and other mechanisms.
AB  - Initiation of excretory system development in all vertebrates requires (1)
      delamination of the pronephric and pronephric duct rudiments from intermediate
      mesoderm at the ventral border of anterior somites, and (2) extension of the
      pronephric duct to the cloaca. Pronephric duct extension is the central event in
      nephric system development; the pronephric duct differentiates into the tubule
      that carries nephric filtrate out of the body and induces terminal
      differentiation of adult kidneys. Early studies concluded that pronephric ducts
      formed by means of in situ segregation of pronephric duct tissue from lateral
      mesoderm ventral to the forming somites; more recent studies highlight caudal
      migration of the pronephric duct as the major morphogenetic mechanism. The
      purpose of this review is to provide the historical background on studies of the
      mechanisms of amphibian pronephric duct extension, to review evidence showing
      that different amphibians perform pronephric duct morphogenesis in different
      ways, and to suggest future studies that may help illuminate the molecular basis
      of the mechanisms that have evolved in amphibians to extend the pronephric duct
      to the cloaca.

PMID- 12508220
TI  - Xenopus muscle development: from primary to secondary myogenesis.
AB  - Xenopus myogenesis is characterized by specific features, different from those of
      mammalian and avian systems both at the cellular level and in gene expression
      patterns. During early embryogenesis, after the initial molecular signals
      inducing mesoderm, the myogenic determination factors XMyoD and XMyf-5 are
      activated in presomitic mesoderm in response to mesoderm-inducing factors. After
      these first inductions of the myogenic program, forming muscles in Xenopus can
      have different destinies, some of these resulting in cell death before adulthood.
      In particular, it is quite characteristic of this species that, during
      metamorphosis, the primary myotomal myofibers completely die and are
      progressively replaced by secondary "adult" multinucleated myofibers. This
      feature offers the unique opportunity to totally separate the molecular analysis
      of these two distinct types of myogenesis. The aim of this review is to summarize
      our knowledge on the cellular and molecular events as well as the epigenetic
      regulations involved in the construction of Xenopus muscles during development.

PMID- 12508221
TI  - Rho-associated kinases play an essential role in cardiac morphogenesis and
      cardiomyocyte proliferation.
AB  - Rho-associated coiled-coil kinases (ROCKs), initially identified as effectors for
      Rho GTPases, play a role in cardiac cell physiology and are also expressed in the
      developing heart. However, their role in cardiac development is not known. To
      investigate the role of these kinases in cardiac development, we examined cardiac
      development in cultured murine embryos treated with the ROCK inhibitor Y27632.
      After inhibition of ROCK activity, we found disturbed cardiac chamber formation
      and trabeculation. To further examine the mechanisms by which ROCK blockade
      causes cardiac hypoplasia, we assessed programmed cell death and cell
      proliferation in the hearts. We found decreased cell proliferation in the Y27632
      treated hearts, but no changes in programmed cell death. We further observed that
      ROCK inhibition decreased cardiac myocyte proliferation, suggesting that ROCK
      kinases regulate cardiomyocyte division. To identify factors involved in ROCK
      action in regulation of cardiac cell division, we examined expression of cell
      cycle proteins by using Western blot analysis. We found that ROCK blockade
      decreased expression of cell cycle proteins, cyclin D3, CDK6, and p27(KIP1) in
      the hearts and cardiomyocytes, which are required for initiation of cell cycle
      and G1/S phase transition. These observations show that ROCK kinases play a role
      in cardiac development and that ROCK kinases regulate cardiac cell proliferation
      and cell cycle protein expression.

PMID- 12508222
TI  - Heart-selective expression of the chicken FK506-binding protein (FKBP) 12.6 gene
      during embryonic development.
AB  - FKBP12.6, a member of the family of FK506-binding proteins, selectively
      associates with the cardiac isoform of the ryanodine receptor and thereby
      stabilizes this Ca(2+) release channel. A chicken FKBP12.6 (chFKBP12.6) cDNA was
      cloned and shown to encode a protein of 108 amino acids. The deduced amino acid
      sequence of chFKBP12.6 is 91-92% identical to those of mammalian FKBP12.6
      proteins. Northern blot analysis revealed that chFKBP12.6 mRNA is largely
      restricted to the heart during embryonic development and that the abundance of
      this mRNA in the heart decreases, and it becomes restricted to the atrium during
      cardiogenesis. In situ hybridization revealed that chFKBP12.6 mRNA is localized
      to the precardiac mesoderm before formation of the primitive heart tube.
      Expression of the chFKBP12.6 gene was initially apparent throughout the
      developing multichambered heart but became restricted to the atria before
      hatching. Reverse transcription and polymerase chain reaction analysis
      demonstrated that chFKBP12.6 mRNA is present in the embryo from early
      gastrulation and is most abundant immediately after the onset of the heartbeat.
      These observations suggest that the chFKBP12.6 gene is expressed before heart
      morphogenesis to play a role in excitation-contraction coupling in cardiomyocytes
      and that the function of the encoded protein becomes increasingly restricted to
      the atrium during embryonic development.

PMID- 12508223
TI  - Developmental expression of the HNK-1 carbohydrate epitope on aggrecan during
      chondrogenesis.
AB  - Previously, we showed that the HNK-1 carbohydrate epitope is expressed on
      aggrecan synthesized in the notochord but not in mature cartilage. In the present
      study, we demonstrate that in immature cartilage (embryonic day 6) the HNK-1
      epitope is also expressed predominantly on aggrecan proteoglycan molecules. This
      finding was verified by using an aggrecan-deficient mutant, the nanomelic chick,
      which lacks HNK-1 immunostaining in the extracellular matrix of dividing and
      hypertrophic chondrocytes as late as embryonic day 12. By using both biochemical
      and immunologic approaches, the initially prominent expression of the HNK-1
      epitope is down-regulated as development of limb and vertebral cartilage
      proceeds, so that by embryonic day 14 no HNK-1 is detectable. Localization
      changes with development and the HNK-1-aggrecan matrix becomes restricted to
      dividing and hypertrophic chondrocytes and is particularly concentrated in the
      intraterritorial matrix. Concomitant with the temporal and spatial decreases in
      HNK-1, there is a significant increase in keratan-sulfate content and the
      aggrecan-borne HNK-1 epitope is closely associated with proteolytic peptides that
      contain keratan sulfate chains, rather than chondroitin sulfate chains or
      carbohydrate-free domains. Lastly, the diminution in HNK-1 expression is
      consistent with a reduction in mRNA transcripts specific for at least one of the
      key enzymes in HNK-1 oligosaccharide biosynthesis, the HNK-1 sulfotransferase.
      These findings indicate that the HNK-1 carbohydrate may be a common modifier of
      several proteoglycans (such as aggrecan) that are usually expressed early in
      development, and that HNK-1 addition to these molecules may be regulated by
      tissue- and temporal-specific expression of requisite sulfotransferases and
      glycosyltransferases.

PMID- 12508224
TI  - T-box binding site mediates the dorsal activation of myf-5 in Xenopus gastrula
      embryos.
AB  - Myf-5, a member of the muscle regulatory factor family of transcription factors,
      plays an important role in the determination, development, and differentiation of
      the skeletal muscle. Factors that regulate the expression of myf-5 itself are not
      well understood. We show here that a T-box binding site in the Xenopus myf-5
      promoter mediated the activation of myf-5 expression through specific interaction
      with nuclear proteins of gastrula embryos. The T-box binding site could be bound
      by and respond to T-box proteins. T-box genes could induce Xmyf-5. The results
      suggest that T-box proteins are involved in the specification of myogenic
      mesoderm and muscle development.

PMID- 12508225
TI  - Cyclops-independent floor plate differentiation in zebrafish embryos.
AB  - In zebrafish, development of the ventral neural tube depends on the Nodal-related
      signal Cyclops (Cyc). One-day-old cyc mutant embryos lack the medial floor plate
      (MFP). We show here that cells expressing MFP marker genes differentiate
      gradually in cyc mutant embryos in a delayed manner during the second day of
      development. This late differentiation is restricted to the hindbrain and spinal
      cord and depends on an intact Hedgehog (Hh) signalling pathway. Cells expressing
      MFP marker genes in cyc mutant embryos appear to be derived from lateral floor
      plate (LFP) cells as they coexpress LFP and MFP marker genes. This finding
      suggests that the correct temporal development of the MFP is required for the
      distinction of LFP and MFP cells in wild-type embryos.

PMID- 12508226
TI  - Drosophila NAB (dNAB) is an orphan transcriptional co-repressor required for
      correct CNS and eye development.
AB  - The mammalian NAB proteins have been identified previously as potent co
      repressors of the EGR family of zinc finger transcription factors. Drosophila NAB
      (dNAB), like its mammalian counterparts, binds EGR1 and represses EGR1-mediated
      transcriptional activation from a synthetic promoter. In contrast, dNAB does not
      bind the Drosophila EGR-related protein klumpfuss. dnab RNA is expressed
      exclusively in a subset of neuroblasts in the embryonic and larval central
      nervous system (CNS), as well as in several larval imaginal disc tissues. Here,
      we describe the creation of targeted deletion mutations in the dnab gene and the
      identification of additional, EMS-induced dnab mutations by genetic
      complementation analysis. Null alleles in dnab cause larval locomotion defects
      and early larval lethality (L1-L2). A putative hypomorphic allele in dnab instead
      causes early adult lethality due to severe locomotion defects. In the dnab -/-
      CNS, axon outgrowth/guidance and glial development appear normal; however, a
      subset of eve+ neurons forms in reduced numbers. In addition, mosaic analysis in
      the eye reveals that dnab -/- clones are either very small or absent. Similarly,
      dNAB overexpression in the eye causes eyes to be very small with few ommatidia.
      These dramatic eye-specific phenotypes will prove useful for enhancer/suppressor
      screens to identify dnab-interacting genes.

PMID- 12508227
TI  - T-box gene products are required for mesenchymal induction of epithelial
      branching in the embryonic mouse lung.
AB  - The regulation of signaling pathways is a prerequisite for coordinating the
      induction between mesenchymal and epithelial tissues during morphogenesis.
      Mesenchymal FGF10 is known to be an important paracrine factor regulating the
      branching morphogenesis of the bronchial epithelium. By using antisense
      oligonucleotides (AS ODNs) and in vitro culture of embryonic lungs, we
      demonstrate that the transcription factors Tbx4 and Tbx5 are critical for the
      expression of mesenchymal FGF10. Treatment of embryonic lung cultures with AS
      ODNs to Tbx4 and Tbx5 reduces the level of these transcripts, suppresses Fgf10
      expression in the mesenchyme, and completely eliminates the formation of new lung
      branches. If FGF10 is locally replaced in these AS ODN-treated lungs, epithelial
      branching is restored. These studies provide evidence that the production of
      branching signals by the lung mesenchyme is mediated by T-box genes.

PMID- 12508228
TI  - Appearance of neurons and glia with respect to the wavefront during colonization
      of the avian gut by neural crest cells.
AB  - The enteric nervous system is formed by neural crest cells that migrate,
      proliferate, and differentiate into neurons and glia distributed in ganglia along
      the gastrointestinal tract. In the developing embryo some enteric crest cells
      cease their caudal movements, whereas others continue to migrate. Subsequently,
      the enteric neurons form a reticular network of ganglia interconnected by axonal
      projections. We studied the developing avian gut to characterize the pattern of
      migration of the crest cells, and the relationship between migration and
      differentiation. Crest cells at the leading edge of the migratory front appear as
      strands of cells; isolated individual crest cells are rarely seen. In the foregut
      and midgut, these strands are located immediately beneath the serosa. In
      contrast, crest cells entering the colon appear first in the deeper submucosal
      mesenchyme and later beneath the serosa. As the neural crest wavefront passes
      caudally, the crest cell cords become highly branched, forming a reticular
      lattice that presages the mature organization of the enteric nervous system.
      Neurons and glia first appear within the strands at the advancing wavefront.
      Later neurons are consistently located at the nodes where branches of the lattice
      intersect. In the most rostral foregut and in the colon, some neurons initially
      appear in close association with extrinsic nerve fibers from the vagus and
      Remak's nerve, respectively. We conclude that crest cells colonize the gut as
      chains of cells and that, within these chains, both neurons and glia appear close
      to the wavefront.

PMID- 12508229
TI  - Genetic linkage maps of the West African clawed frog Xenopus tropicalis.
AB  - Amphibians, and particularly the African clawed frog Xenopus laevis, have been
      used for more than a century as models of vertebrate embryonic development.
      However, in many cases, elucidation of developmental functions of specific gene
      sequences could be severely impeded, because X. laevis is a tetraploid species,
      with multiple functional copies of many genes of interest. Recent studies have
      shifted focus to the West African or tropical clawed frog, X. tropicalis, the
      only known diploid species of the genus Xenopus. Here, we present two preliminary
      linkage maps, constructed by analysis of joint segregation of amplified fragment
      length polymorphism (AFLP) markers in a X. tropicalis interstrain hybrid. A total
      of 53 markers, including 51 AFLP markers and 2 isozyme markers, are presently
      assigned to 13 multipoint linkage groups on a map of the maternal strain, whereas
      9 AFLP markers from the paternal strain are assigned to 3 linkage groups on a
      separate map. A dense genetic linkage map is essential in mapping new
      developmental mutants and determining their sequences by positional cloning.

PMID- 12508230
TI  - Expression of Sox9 in granulosa cells lacking the estrogen receptors, ERalpha and
      ERbeta.
AB  - Ovaries from adult mice lacking both estrogen receptors ERalpha and ERbeta
      (ERalphabetaKO mice) contain abnormal cells sharing morphologic features with
      Sertoli cells, which are located mainly in the interstitial compartment. We show
      here that these cells express the Sertoli cell markers TIF1beta, TIF2, and Sox9.
      In ERalphabetaKO ovaries, Sox9 is expressed by granulosa cells before the
      morphologic appearance of Sertoli cells, but neither by granulosa cell precursors
      nor by non-Sertolian interstitial cells. These findings suggest that functional
      Sertoli cells can transdifferentiate from mature granulosa cells devoid of
      estrogen receptors as a result of Sox9 expression.

PMID- 12508231
TI  - In ovo electroporation of Crim1 in the developing chick spinal cord.
AB  - The novel mammalian gene Crim1 encodes a transmembrane bound protein with
      similarity to the secreted bone morphogenetic protein (BMP) antagonists,
      vertebrate Chordin, and its Drosophila homologue short gastrulation. Crim1 is
      expressed in the neural tube in mouse in a restricted pattern, but its function
      in central nervous system development is largely unknown. We isolated the chicken
      Crim1 orthologue and analyzed its expression in the developing neural tube.
      Chicken CRIM1 shares strong homology to human/mouse CRIM1 and C. elegans CRIM1
      like proteins. Crim1 is expressed in a similar but not identical pattern to that
      in the developing spinal cord of mouse, including the notochord, floor plate,
      motor neurons, and the roof plate. Unlike follistatin, a secreted inhibitor of
      BMPs, in ovo electroporation of CRIM1, as a full-length transmembrane bound or
      secreted ectodomain was not sufficient to disrupt early patterning of the neural
      tube. However, ectodomain CRIM1 overexpression leads to an approximate 50%
      decrease in populations of specific ventral neuronal populations, including ISL
      1(+) motor neurons, CHX-10(+) V1, and EN-1(+) V2 interneurons.

PMID- 12508232
TI  - Spatial and temporal expression of folate-binding protein 1 (Fbp1) is closely
      associated with anterior neural tube closure in mice.
AB  - Periconceptional folate supplementation is widely believed to have significant
      preventive effects on the production of neural tube defects. Folate-binding
      protein 1 (FBP1) is one of the membrane proteins that mediate cellular uptake of
      folate. Although recent studies suggest that Fbp1 is essential for neural tube
      closure, the pattern of Fbp1 expression in embryonic tissues has not been
      examined in detail. To elucidate how Fbp1 contributes to neural tube closure, we
      examined the spatial and temporal expression patterns of Fbp1 in the developing
      neural folds and tube of mouse embryos by in situ hybridization. Fbp1 showed a
      distinct expression pattern in the neural folds, which preceded initiation of
      neural tube closure at the cervical region and the prosencephalic/mesencephalic
      boundary. Fbp1 expression was mainly localized to the most dorsal regions of the
      neural folds where fusion was to occur. With proceeding of neural fold fusion,
      Fbp1 expression extended to the adjacent unfused neural folds. In the
      rhombencephalon, robust expression of Fbp1 was observed in rhombomere2 (r2) and
      r6, suggesting its roles in development of neural crest cells. Fbp1 also showed
      intense expression in the yolk sac, indicating that FBP1 may mediate transferring
      maternal folate to embryos during neurulation. These findings indicate close
      association between Fbp1 and anterior neural tube closure.

PMID- 12508233
TI  - Molecular components of the endoderm specification pathway in Xenopus tropicalis.
AB  - Xenopus laevis has been instrumental in elucidating a conserved molecular pathway
      that regulates vertebrate endoderm specification. However, loss-of-function
      analysis is required to resolve the precise function of the genes involved. For
      such analysis, antisense oligos and possibly forward genetics are likely to be
      more effective in the diploid species Xenopus tropicalis than in the
      pseudotetraploid Xenopus laevis. Here we have isolated most of the tropicalis
      genes in the endoderm specification pathway, specifically, tVegT, tMixer, tMix,
      tBix, tGata6, tSox17alpha, tSox17beta, tFoxA1, tHex, and tCerberus, which lack
      the redundant copies that are found in laevis. In situ hybridization analysis has
      revealed identical expression patterns between the orthologous tropicalis and
      laevis endoderm genes, thus suggesting conserved genetic functions. Furthermore,
      we noted that the smaller tropicalis embryos gave better probe penetration than
      in laevis whole-mount in situ hybridizations-allowing us to visualize transcripts
      in the deep endoderm in tropicalis, which is difficult in laevis. This study
      illustrates how an entire genetic pathway can be quickly transferred from laevis
      to tropicalis due to high sequence conservation between the sister species and
      the large number of tropicalis-expressed sequence tags that are now available.

PMID- 12508234
TI  - Genome-wide examination of myoblast cell cycle withdrawal during differentiation.
AB  - Skeletal and cardiac myocytes cease division within weeks of birth. Although
      skeletal muscle retains limited capacity for regeneration through recruitment of
      satellite cells, resident populations of adult myocardial stem cells have not
      been identified. Because cell cycle withdrawal accompanies myocyte
      differentiation, we hypothesized that C2C12 cells, a mouse myoblast cell line
      previously used to characterize myocyte differentiation, also would provide a
      model for studying cell cycle withdrawal during differentiation. C2C12 cells were
      differentiated in culture medium containing horse serum and harvested at various
      time points to characterize the expression profiles of known cell cycle and
      myogenic regulatory factors by immunoblot analysis. BrdU incorporation decreased
      dramatically in confluent cultures 48 hr after addition of horse serum, as cells
      started to form myotubes. This finding was preceded by up-regulation of MyoD,
      followed by myogenin, and activation of Bcl-2. Cyclin D1 was expressed in
      proliferating cultures and became undetectable in cultures containing 40% fused
      myotubes, as levels of p21(WAF1/Cip1) increased and alpha-actin became
      detectable. Because C2C12 myoblasts withdraw from the cell cycle during myocyte
      differentiation following a course that recapitulates this process in vivo, we
      performed a genome-wide screen to identify other gene products involved in this
      process. Using microarrays containing approximately 10,000 minimally redundant
      mouse sequences that map to the UniGene database of the National Center for
      Biotechnology Information, we compared gene expression profiles between
      proliferating, differentiating, and differentiated C2C12 cells and verified
      candidate genes demonstrating differential expression by RT-PCR. Cluster analysis
      of differentially expressed genes revealed groups of gene products involved in
      cell cycle withdrawal, muscle differentiation, and apoptosis. In addition, we
      identified several genes, including DDAH2 and Ly-6A, whose expression
      specifically was up-regulated during cell cycle withdrawal coincident with early
      myoblast differentiation.

PMID- 12508235
TI  - Targeted disruption of mouse Dach1 results in postnatal lethality.
AB  - Mouse Dach1 is a nuclear factor that is expressed during development in
      restricted areas of the central nervous system, neural crest, and limb buds. Its
      Drosophila homologue dachshund plays a role in differentiation of the eye
      imaginal disc, in leg morphogenesis, and in controlling neural differentiation in
      the mushroom bodies of the insect brain. Mouse Dach1 null homozygous survive
      pregnancy but become cyanotic after birth and subsequently die within 24 hr. In
      this report, the brain of Dach1 mutants was analyzed. Examination of mRNA
      expression of the central neuropeptides oxytocin, vasopressin, thyrotropin
      releasing hormone, growth hormone releasing hormone, and somatostatin revealed no
      difference between wild-type and mutant newborn brains. Furthermore, no
      significant difference in cell proliferation as well as in the distribution of
      neurons, glia, radial glia, and neuronal progenitors was detected in the
      developing forebrain. Dach1-positive cells, which were visualized with Enhanced
      Green Fluorescent Protein (EGFP), show similar distribution and axonal
      projections in the cortex and hippocampus in mutants and wild-type controls.
      Neural stem cells derived from mutant and wild-type newborn brains display
      similar growth kinetics when cultivated in vitro.

PMID- 12508236
TI  - Ci-GATAa, a GATA-class gene from the ascidian Ciona intestinalis: isolation and
      developmental expression.
AB  - Members of the GATA family of zinc finger transcription factors have been shown
      to play important roles in controlling gene expression in a variety of cell types
      in many metazoan. Here, we describe the identification of Ci-GATAa, a member of
      this gene family, in the ascidian Ciona intestinalis. Whole-mount in situ
      hybridization showed that Ci-GATAa was expressed in a highly dynamic manner. The
      maternal transcript was evenly distributed in the embryo during early stages of
      development; however, the signal gradually decreased until it disappeared at the
      64-cell stage. A zygotic transcript was detected at the 110-cell stage in the
      blastomeres precursors of three different tissues (brain vesicle, mesenchyme, and
      trunk lateral cells) and the signal was conserved in these territories up to the
      larval stage, indicating an important role for Ci-GATAa during ascidian
      differentiation.

PMID- 12508237
TI  - Chick limbs with mouse teeth: an effective in vivo culture system for tooth germ
      development and analysis.
AB  - Mouse tooth germ development is currently studied by three main approaches: in
      wild-type and mutant mouse lines, after transplantation of tooth germs to ectopic
      sites, and in organ culture. The in vivo approaches are the most physiological
      but do not provide accessibility to tooth germs for further experimental
      manipulation. Organ cultures, although readily accessible, do not sustain full
      tooth germ development and are appropriate for short-term analysis. Thus, we
      sought to establish a new approach that would combine experimental accessibility
      with sustained development. We implanted fragments of embryonic day 12 mouse
      embryo first branchial arch containing early bud stage tooth germs into the
      lateral mesenchyme of day 4-5 chick embryo wing buds in ovo. Eggs were
      reincubated, and implanted tissues were examined by histochemistry and in situ
      hybridization over time. The tooth germs underwent seemingly normal growth,
      differentiation, and morphogenesis. They reached the cap, bell, and crown stages
      in approximately 3, 6, and 10 days, respectively, mimicking in a striking manner
      native temporal patterns. To examine mechanisms regulating tooth germ
      development, we first implanted tooth germ fragments, microinjected them with
      neutralizing antibodies to the key signaling molecule Sonic hedgehog (Shh), and
      examined them over time. Tooth germ development was markedly delayed, as revealed
      by poor morphogenesis and lack of mature ameloblasts and odontoblasts displaying
      characteristic traits such as an elongated cell shape, nuclear relocalization,
      and amelogenin gene expression. These phenotypic changes began to be reversed
      upon further incubation. The data show that the limb bud represents an effective,
      experimentally accessible as well as economical system for growth and analysis of
      developing tooth germs. The inhibitory effects of Shh neutralizing antibody
      treatment are discussed in relation to roles of this signaling pathway proposed
      by this and other groups previously.

PMID- 12508238
TI  - Transitions in the model of epithelial patterning.
AB  - We analyze pattern formation in the model of cell communication in Drosophila egg
      development. The model describes the regulatory network formed by the epidermal
      growth factor receptor (EGFR) and its ligands. The network is activated by the
      oocyte-derived input that is modulated by feedback loops within the follicular
      epithelium. We analyze these dynamics within the framework of a recently proposed
      mathematical model of EGFR signaling (Shvartsman et al. [2002] Development
      129:2577-2589). The emphasis is on the large-amplitude solutions of the model
      that can be correlated with the experimentally observed patterns of protein and
      gene expression. Our analysis of transitions between the major classes of
      patterns in the model can be used to interpret the experimentally observed
      phenotypic transitions in eggshell morphology in Drosophila melanogaster. The
      existence of complex patterns in the model can be used to account for complex
      eggshell morphologies in related fly species.

PMID- 12508239
TI  - The IGFI receptor gene: a molecular target for disrupted transcription factors.
AB  - The biological actions of the insulin-like growth factors, IGFI and IGFII, are
      mediated by their activation of the IGFI receptor (IGFIR), a transmembrane
      heterotetramer linked to the RAS-RAF-MAPK and PI3K-PKB/AKT signal transduction
      cascades. The IGFIR displays potent mitogenic, antiapoptotic, and transforming
      activities, and is a prerequisite for oncogenic transformation. A number of
      transcription factors have been identified that control the expression of this
      gene and therefore determine, to a significant extent, the proliferative status
      of the cell. The purpose of this review is to summarize data showing that, under
      normal physiological conditions, expression of the IGFIR is under inhibitory
      control by a family of negative growth regulators or tumor suppressors. Cells
      with a reduced number of cell-surface receptors are unable to progress through
      the cell cycle and remain in a postmitotic state. Loss-of-function mutation of
      tumor suppressors in certain cancers results in transcriptional derepression of
      the IGFIR gene, with ensuing increases in the levels of IGFIR and increased
      proliferative capacity. Understanding the molecular mechanisms responsible for
      transcriptional regulation of the IGFIR gene will prove important in designing
      novel therapies aimed at targeting the IGF axis.

PMID- 12508240
TI  - Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies
      chromosomal regions associated with histopathology, progression, and patient
      outcome.
AB  - Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of
      comparative genomic hybridization (CGH), and clinical/histological correlations
      were performed. Adverse histological factors were present in 13 patients.
      Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain
      of 6p represented the most frequent event (69% of the tumors), whereas +1q was
      observed in 57%, confirming that these abnormalities are key secondary events in
      retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated
      with tumors displaying adverse histo-prognostic factors, whereas -16q was
      significantly associated with tumors without adverse features. In three patients
      who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q,
      suggesting that these abnormalities may be associated with metastasis. Children
      >or= 36 months of age at enucleation tended to have more CGH abnormalities per
      tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q,
      +13q, -16, and -16q were more frequent in children with an older age at
      enucleation. Identical CGH changes were found in both tumors from one patient
      with bilateral tumors, suggesting a common origin. It is possible that tumors
      displaying loss of 13q and 5q indicate those patients who may suffer an adverse
      outcome and who would require alternative or more intensive therapy. CGH analysis
      on larger cohorts and in prospective clinical trials will be invaluable in
      determining whether a genetic classification of retinoblastoma represents a
      reliable measure of prognosis.

PMID- 12508241
TI  - Hypermethylation-mediated regulation of CD44 gene expression in human
      neuroblastoma.
AB  - The CD44 adhesion receptor is silenced in highly malignant neuroblastomas (NBs)
      with MYCN amplification. Because its functional expression is associated with
      decreased tumorigenic properties, CD44 behaves as a tumor suppressor gene in NB
      and other cancers. Given that the precise mechanisms responsible for CD44
      silencing are not elucidated, we investigated whether CD44 expression could be
      regulated by DNA hypermethylation. The methylation status of CD44 gene promoter
      and exon 1 regions was analyzed in 12 NB cell lines and 21 clinical samples after
      bisulfite genomic modification, followed by PCR and single-strand conformation
      polymorphism analysis and genomic sequencing. The results showed that almost all
      CD44-negative cell lines displayed hypermethylation in both regions, whereas all
      CD44-expressing cell lines were unmethylated. These observations correlated with
      the ability to restore CD44 mRNA and protein expression by treatment of CD44
      negative cells with the 5-aza-2'-deoxycytidine demethylating agent. In contrast,
      no CD44 gene hypermethylation could be detected in 21 NB clinical samples of
      different stages, irrespective of CD44 expression. Although our results suggest
      that aberrant methylation of promoter and exon 1 regions is involved in CD44
      silencing in NB cell lines, they also indicate that methylation of unidentified
      regulatory sequences or methylation-independent mechanisms also control the
      expression of CD44 in primary NB tumors and cell lines. We therefore conclude
      that CD44 silencing is controlled by complex and tumor cell-specific processes,
      including gene hypermethylation. Further investigation of other mechanisms and
      genes involved in CD44 regulation will be needed before demethylation-mediated
      reactivation of the CD44 gene can be considered as therapeutic strategy for
      neuroblastoma and perhaps other related cancers.

PMID- 12508242
TI  - Chromosomes that show partial loss or gain in near-diploid tumors coincide with
      chromosomes that show whole loss or gain in near-triploid tumors: evidence
      suggesting the involvement of the same genes in the tumorigenesis of high- and
      low-risk neuroblastomas.
AB  - We performed two-color fluorescence in situ hybridization analysis to detect the
      numbers of chromosomes 1 and 17, 1p deletion, and 17q gain in 177 neuroblastomas,
      including 101 tumors that were found by a mass-screening program for infants.
      Sixty-eight tumors with disomy 1 or tetrasomy 1 were classified as the Dis1
      group, and 109 tumors with trisomy 1, pentasomy 1, or a mixed population of cells
      with trisomy 1 and cells with tetrasomy 1 were classified as the Tris1 group. 17q
      gain was the most frequent genetic event, followed by 1p deletion, and MYCN
      amplification in both Dis1 and Tris1 tumors. However, the incidence of all the
      genetic events was higher in Dis1 tumors than in Tris1 tumors. These findings
      suggest that Tris1 tumors are more resistant to acquiring the genetic events than
      are Dis1 tumors. In addition, there was an accumulation of genetic events in more
      advanced stages, with the exception of a high incidence of 17q gain in the stage
      IVS Tris1 tumors. Comparative genomic hybridization analysis, which was performed
      in 59 of the 177 tumors, showed that chromosomes partially lost or gained in Dis1
      tumors coincided with chromosomes totally lost or gained in Tris1 tumors. Dis1
      and Tris1 tumors were considered to have near-diploid/tetraploid and near
      triploid/pentaploid chromosome numbers, respectively. These findings suggest that
      the same tumor-suppressor genes or oncogenes may be involved in the development
      and progression of both high- and low-risk neuroblastomas, and that the ploidy
      state of the tumor plays a fundamental role in the heterogeneous behavior.

PMID- 12508243
TI  - Distinct chromosomal aberrations in sinonasal mucosal melanoma as detected by
      comparative genomic hybridization.
AB  - Sinonasal mucosal melanomas are the most frequent mucosal melanomas and arise
      from melanocytes located in the nasal cavity and the paranasal sinuses. The
      melanoma types, cutaneous melanoma, uveal melanoma, and mucosal melanoma, differ
      in etiology, geographic distribution, and clinical behavior. Genetic alterations
      have been previously studied in cutaneous and uveal melanomas but, to the best of
      our knowledge, not in mucosal melanomas. Comparative genomic hybridization (CGH)
      was performed on 14 routinely processed sinonasal mucosal melanomas. Furthermore,
      ploidy analysis was performed on 11 tumors to provide complementary data on the
      DNA index. The CGH profiles of sinonasal mucosal melanomas show remarkably
      consistent alterations: chromosome arm 1q is gained in all tumors and gains of 6p
      and 8q are present in 93 and 57%, respectively. Comparison of CGH data with both
      the common variants of cutaneous melanoma and uveal melanoma revealed that
      sinonasal mucosal melanomas harbor a distinct pattern of chromosomal
      abnormalities. Ploidy analysis also showed that diploid tumors exhibit gains of
      1q and alterations of chromosome 6 (3 of 3 cases tested), whereas clear-copy
      gains and high-copy gains were seen only in triploid and tetraploid tumors (6 of
      8 cases tested). This indicates that alteration of chromosomes 1 and 6 may
      precede polyploidization and formation of clear-copy gains and high-copy gains.

PMID- 12508244
TI  - High-resolution genomic profiling of occult micrometastatic tumor cells.
AB  - Metastasis is responsible for most deaths from cancer. Currently, little is known
      about the early genetic events in the metastatic evolution. Here we describe the
      application of a newly developed strategy for an in-depth characterization of
      genomic changes in micrometastatic cells. Unique tumor cell lines were
      established from bone marrow of patients with cancer of the prostate and analyzed
      by multiplex-FISH (M-FISH) and array CGH. M-FISH revealed that the occult
      disseminated cells were characterized by very complex numerical and structural
      aberrations. Many of these aberrations resulted in chromosomal gains and losses,
      such as losses of 8p, 13q, and 18q and gains of 8q, 9q, 20, and the X chromosome,
      which are typically observed in prostate cancer. Array CGH allowed an
      unprecedented high-resolution assessment of copy number changes, pinpointing
      commonly gained or lost regions, which should narrow down the identification of
      regions critically involved in metastasis. Thus, occult micrometastatic cells are
      now amenable to detailed analyses of their genome. Markers for prognosis and
      treatment decisions can now be established.

PMID- 12508245
TI  - Establishment of the acute myeloid leukemia cell line Kasumi-6 from a patient
      with a dominant-negative mutation in the DNA-binding region of the C/EBPalpha
      gene.
AB  - A myeloid leukemia cell line designated Kasumi-6 was established from the bone
      marrow cells of an individual with acute myeloid leukemia, subtype M2. Both the
      original leukemic cells and the Kasumi-6 cell line harbor a hemizygous point
      mutation in the gene encoding the CCAAT/enhancer binding protein alpha
      (C/EBPalpha), a critical myeloid transcriptional factor. The C to G transition at
      nucleotide 1063 of the C/EBPalpha gene results in amino acid transition R305P in
      the fork or hinge region between the DNA-binding basic region and the leucine
      zipper dimerization domain of the C/EBPalpha protein. The Kasumi-6 cells
      expressed both the p42 and p30 isoforms of the C/EBPalpha protein endogenously,
      but electrophoretic mobility shift assays demonstrated an absence of C/EBPalpha
      binding to its respective site. Exogenous expression of the mutant form of
      C/EBPalpha demonstrated that it was unable to bind DNA and activate transcription
      from a G-CSF receptor-luciferase reporter construct. Furthermore, coexpression of
      the wild-type and mutant forms revealed that the mutant form repressed reporter
      gene activation by the wild type in a dose-responsive manner. This was
      concomitant with a dose-responsive decrease in wild-type protein binding to the G
      CSF receptor C/EBP site. The data suggest that the R305P alteration confers a
      dominant-negative property on the mutant C/EBPalpha protein whereby the mutant
      polypeptide heterodimerizes with the wild-type polypeptide and prevents it from
      binding to DNA, thus blocking transcriptional activation. The Kasumi-6 cell line
      can serve as a model to study the cellular and molecular biology of the non
      t(8;21) M2 type of myeloid leukemia and can elucidate the role of mutated
      C/EBPalpha in leukemogenesis.

PMID- 12508246
TI  - Genomic anatomy of the specific reciprocal translocation t(15;17) in acute
      promyelocytic leukemia.
AB  - The genomic breakpoints in the t(15;17)(q22;q21), associated with acute
      promyelocytic leukemia (APL), are known to occur within three different PML
      breakpoint cluster regions (bcr) on chromosome 15 and within RARA intron 2 on
      chromosome 17; however, the precise mechanism by which this translocation arises
      is unclear. To clarify this mechanism, we (i). assembled the sequence of RARA
      intron 2, (ii). amplified and sequenced the genomic PML-RARA junction sequences
      from 37 APL patients, and (iii). amplified and sequenced the reverse RARA-PML
      genomic fusion in 29 of these cases. Three significant breakpoint microclusters
      within RARA intron 2 were identified, suggesting that sequence-associated or
      structural factors play a role in the formation of the t(15;17). There was no
      evidence that the location of a breakpoint in PML had any relationship to the
      location of the corresponding breakpoint in RARA. Although some sequence motifs
      previously implicated in illegitimate recombinations were found in the
      microcluster regions, these associations were not significant. Comparison of
      forward and reverse genomic junctions revealed microhomologies, deletions, and/or
      duplications of either gene in all but one case, in which a complex rearrangement
      with inversion of the PML-derived sequence was found. These findings are
      consistent with the hypothesis that the t(15;17) occurs by nonhomologous
      recombination of DNA after processing of the double-strand breaks by a
      dysfunctional DNA damage-repair mechanism.

PMID- 12508247
TI  - Genetic profiling of colorectal cancer liver metastases by combined comparative
      genomic hybridization and G-banding analysis.
AB  - The majority of genetic studies of colorectal carcinogenesis have focused on
      changes found in primary tumors. Despite the fact that liver metastases are a
      leading cause of colorectal cancer deaths, the molecular genetic basis of the
      advanced disease stages remains poorly understood. We performed comparative
      genomic hybridization (CGH) on 17 liver metastases from colorectal carcinomas and
      compared the quantitative profile with the qualitative profile previously
      obtained with chromosome banding. An average of 12.6 aberrations per tumor was
      found by CGH. Chromosome 18 and chromosome arms 4q, 8p, and 17p were most
      frequently lost, whereas chromosomes 7 and 20 and chromosome arms 6p, 8q, and 13q
      were most frequently gained. We compared the chromosome banding and CGH data
      after converting the karyotypes into net copy number gains and losses. Ten tumors
      showed agreement between the findings of the two techniques, whereas five tumors
      did not (in two cases, no mitotic cells were obtained for banding analysis). All
      five discordant cases had a "simple" abnormal or normal karyotype, but revealed
      multiple changes by CGH. A likely explanation for this discrepancy is that in
      vitro growth before G-banding selected against the cancer cells. Interestingly,
      by comparing the CGH profiles of the "complex" vs. the "simple"/normal karyotype
      groups, deletion of 8p and gain of 16q were seen more frequently in the former
      group. The liver metastases had the same aberrations as seen in primary
      colorectal carcinomas, summarized in a literature survey. However, these
      aberrations were seen more frequently in liver metastases, which may be
      attributable to increased genetic instability.

PMID- 12508248
TI  - New mutations and protein variants of NBS1 are identified in cancer cell lines.
AB  - Alterations of the NBS1 gene are responsible for Nijmegen breakage syndrome
      (NBS), which is characterized by chromosomal instability, radiosensitivity, and
      cancer predisposition. NBS1 protein (Nibrin) is part of a molecular complex (NBS1
      MRE11A-RAD50) that is functionally involved in DNA double-strand-break repair.
      Defects in recombination or in repair mechanisms at the level of DNA breakage can
      lead to chromosomal aberrations, genetic instability, as well as cancer
      predisposition syndromes (i.e., NBS, ataxia-telangiectasia, Bloom syndrome). In
      this study, we examined 20 cancer cell lines to evaluate the potential
      involvement of NBS1 in tumoral pathogenesis. Three different mutations,
      generating truncated or aberrant NBS1 transcripts, were identified at the level
      of NBS1 mRNA. In addition, two shorter NBS1 protein variants were detected in two
      cell lines. These data suggest a possible involvement of NBS1 in tumor
      development.

PMID- 12508249
TI  - Intravenous leiomyomatosis is characterized by a der(14)t(12;14)(q15;q24).
AB  - Intravenous leiomyomatosis (IVL) is a rare smooth-muscle proliferation that is of
      special interest because of its quasi-malignant behavior. Our finding of a
      specific chromosomal aberration, a der(14)t(12;14)(q15;q24), in a second case of
      IVL suggests that it may be characteristic of IVL. We propose that IVL arises
      from a uterine leiomyoma with a t(12;14)(q15;q24). The presence of an extra copy
      of 12q15-qter and/or loss of 14q24-qter may be a critical genetic event(s)
      leading to intravascular intrusion and proliferation.

PMID- 12508250
TI  - Precise breakpoint characterization of the colon adenocarcinoma cell line HT-29
      clone 19A by means of 24-color fluorescence in situ hybridization and multicolor
      banding.

PMID- 12508251
TI  - Detecting genotype combinations that increase risk for disease: maternal-fetal
      genotype incompatibility test.
AB  - Biological mechanisms that involve gene-by-environment interactions have been
      hypothesized to explain susceptibility to complex familial disorders. Current
      research provides compelling evidence that one environmental factor, which acts
      prenatally to increase susceptibility, arises from a maternal-fetal genotype
      incompatibility. Because it is genetic in origin, a maternal-fetal
      incompatibility is one possible source of an adverse environment that can be
      detected in genetic analyses and precisely studied, even years after the adverse
      environment was present. Existing statistical models and tests for gene detection
      are not optimal or even appropriate for identifying maternal-fetal genotype
      incompatibility loci that may increase the risk for complex disorders. We
      describe a new test, the maternal-fetal genotype incompatibility (MFG) test, that
      can be used with case-parent triad data (affected individuals and their parents)
      to identify loci for which a maternal-fetal genotype incompatibility increases
      the risk for disease. The MFG test adapts a log-linear approach for case-parent
      triads in order to detect maternal-fetal genotype incompatibility at a candidate
      locus, and allows the incompatibility effects to be estimated separately from
      direct effects of either the maternal or the child's genotype. Through
      simulations of two biologically plausible maternal-fetal genotype incompatibility
      scenarios, we show that the type-I error rate of the MFG test is appropriate,
      that the estimated parameters are accurate, and that the test is powerful enough
      to detect a maternal-fetal genotype incompatibility of moderate effect size.

PMID- 12508252
TI  - Robustness of inference on measured covariates to misspecification of genetic
      random effects in family studies.
AB  - Family studies to identify disease-related genes frequently collect only families
      with multiple cases. It is often desirable to determine if risk factors that are
      known to influence disease risk in the general population also play a role in the
      study families. If so, these factors should be incorporated into the genetic
      analysis to control for confounding. Pfeiffer et al. [2001 Biometrika 88: 933
      948] proposed a variance components or random effects model to account for common
      familial effects and for different genetic correlations among family members.
      After adjusting for ascertainment, they found maximum likelihood estimates of the
      measured exposure effects. Although it is appealing that this model accounts for
      genetic correlations as well as for the ascertainment of families, in order to
      perform an analysis one needs to specify the distribution of random genetic
      effects. The current work investigates the robustness of the proposed model with
      respect to various misspecifications of genetic random effects in simulations.
      When the true underlying genetic mechanism is polygenic with a small dominant
      component, or Mendelian with low allele frequency and penetrance, the effects of
      misspecification on the estimation of fixed effects in the model are negligible.
      The model is applied to data from a family study on nasopharyngeal carcinoma in
      Taiwan.

PMID- 12508253
TI  - Correcting for nonrandom ascertainment in generalized linear mixed models
      (GLMMs), fitted using Gibbs sampling.
AB  - Gibbs sampling-based generalized linear mixed models (GLMMs) provide a convenient
      and flexible way to extend variance components models for multivariate normally
      distributed continuous traits to other classes of phenotype. This includes binary
      traits and right-censored failure times such as age-at-onset data. The approach
      has applications in many areas of genetic epidemiology. However, the required
      GLMMs are sensitive to nonrandom ascertainment. In the absence of an appropriate
      correction for ascertainment, they can exhibit marked positive bias in the
      estimated grand mean and serious shrinkage in the estimated magnitude of variance
      components. To compound practical difficulties, it is currently difficult to
      implement a conventional adjustment for ascertainment because of the need to
      undertake repeated integration across the distribution of random effects. This is
      prohibitively slow when it must be repeated at every iteration of the Markov
      chain Monte Carlo (MCMC) procedure. This paper motivates a correction for
      ascertainment that is based on sampling random effects rather than integrating
      across them and can therefore be implemented in a general-purpose Gibbs sampling
      environment such as WinBUGS. The approach has the characteristic that it returns
      ascertainment-adjusted parameter estimates that pertain to the true distribution
      of determinants in the ascertained sample rather than in the general population.
      The implications of this characteristic are investigated and discussed. This
      paper extends the utility of Gibbs sampling-based GLMMs to a variety of settings
      in which family data are ascertained nonrandomly.

PMID- 12508254
TI  - Association mapping of complex diseases in linked regions: estimation of genetic
      effects and feasibility of testing rare variants.
AB  - Association mapping in linked regions is a current major approach for the
      identification of genes for complex diseases. Loci contributing to linkage, even
      with small values of sibling recurrence risk (lambda(s)), may be equivalent to
      substantial underlying genetic effects for association studies. For disease
      alleles with a frequency as low as 1%, highly reliable association studies (80%
      power for significance level alpha=10(-6)) require only 277, 781, and 1289
      families or cases and controls for loci detected with lambda(s) of 1.5, 1.1, and
      1.05, respectively, under a multiplicative genetic model. Under alternative
      models, provided epistatic effects are minor, larger achievable sample sizes will
      provide sufficient power to map almost any disease gene that may have initially
      contributed to linkage.

PMID- 12508255
TI  - On a semiparametric test to detect associations between quantitative traits and
      candidate genes using unrelated individuals.
AB  - Although genetic association studies using unrelated individuals may be subject
      to bias caused by population stratification, alternative methods that are robust
      to population stratification such as family-based association designs may be less
      powerful. Recently, various statistical methods robust to population
      stratification were proposed for association studies, using unrelated individuals
      to identify associations between candidate markers and traits of interest (both
      qualitative and quantitative). Here, we propose a semiparametric test for
      association (SPTA). SPTA controls for population stratification through a set of
      genomic markers by first deriving a genetic background variable for each sampled
      individual through his/her genotypes at a series of independent markers, and then
      modeling the relationship between trait values, genotypic scores at the candidate
      marker, and genetic background variables through a semiparametric model. We
      assume that the exact form of relationship between the trait value and the
      genetic background variable is unknown and estimated through smoothing
      techniques. We evaluate the performance of SPTA through simulations both with
      discrete subpopulation models and with continuous admixture population models.
      The simulation results suggest that our procedure has a correct type I error rate
      in the presence of population stratification and is more powerful than
      statistical association tests for family-based association designs in all the
      cases considered. Moreover, SPTA is more powerful than the Quantitative
      Similarity-Based Association Test (QSAT) developed by us under continuous
      admixture populations, and the number of independent markers needed by SPTA to
      control for population stratification is substantially fewer than that required
      by QSAT.

PMID- 12508256
TI  - On selecting markers for association studies: patterns of linkage disequilibrium
      between two and three diallelic loci.
AB  - Association studies depend on linkage disequilibrium (LD) between a causative
      mutation and linked marker loci. Selecting markers that give the best chance of
      showing useful levels of LD with the causative mutation will increase the chances
      of successfully detecting an association. This report examines the variation in
      the extent of LD between a disease locus and one or two diallelic marker loci
      (termed single nucleotide polymorphisms or SNPs). We use a simulation method
      based on the neutral coalescent in a population of variable size to find the
      distribution of LD as a function of allele frequencies, the recombination rate,
      and the population history. Given that LD exists, the allele frequencies
      determine if a site will be useful for detecting an association with the disease
      mutation. We show that there is extensive variation in LD even for closely linked
      loci, implying that several markers may be needed to detect a disease locus. The
      distribution of LD between common variants is strongly influenced by ancestral
      population size. We show that in general, best results will be obtained if the
      frequencies of marker alleles are at least as large as the frequency of the
      causative mutation. Haplotypes of two or more SNPs generally have a higher
      probability than individual SNPs of showing useful LD with a disease mutation,
      although exceptions are described.

PMID- 12508257
TI  - Haplotype sharing analysis with SNPs in candidate genes: the Genetic Analysis
      Workshop 12 example.
AB  - Haplotype sharing analysis was used to investigate the association of affection
      status with single nucleotide polymorphism (SNP) haplotypes within candidate gene
      1 in one sample each from the isolated and the general population of Genetic
      Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct influence on
      affection and harbors more than 70 SNPs. Haplotype sharing analysis depends
      heavily on previous haplotype estimation. Using GENEHUNTER haplotypes, strong
      evidence was found for most SNPs in the isolated population sample, thus
      providing evidence for an involvement of this gene, but the maximum -log(10)(p)
      values for the haplotype sharing statistics (HSS) test statistic did not
      correspond to the location of the true variant in either population. In
      comparison, transmission disequilibrium test (TDT) analysis showed the strongest
      results at the disease-causing variant in both populations, and these were
      outstanding in the general population. In this example, TDT analysis appears to
      perform better than HSS in identifying the disease-causing variant, using SNPs
      within a candidate gene in an outbred population. Simulations showed that the
      performance of HSS is hampered by closely spaced SNPs in strong linkage
      disequilibrium with the functional variant and by ambiguous haplotypes.

PMID- 12508258
TI  - On the use of DNA pooling to estimate haplotype frequencies.
AB  - Genome-wide association studies may be necessary to identify genes underlying
      certain complex diseases. Because such studies can be extremely expensive, DNA
      pooling has been introduced, as it may greatly reduce the genotyping burden.
      Parallel to DNA pooling developments, the importance of haplotypes in genetic
      studies has been amply demonstrated in the literature. However, DNA pooling of a
      large number of samples may lose haplotype information among tightly linked
      genetic markers. Here, we examine the cost-effectiveness of DNA pooling in the
      estimation of haplotype frequencies from population data. When the maximum
      likelihood estimates of haplotype frequencies are obtained from pooled samples,
      we compare the overall cost of the study, including both DNA collection and
      marker genotyping, between the individual genotyping strategy and the DNA pooling
      strategy. We find that the DNA pooling of two individuals can be more cost
      effective than individual genotypings, especially when a large number of
      haplotype systems are studied.

PMID- 12508260
TI  - High plasma fibrinogen level is associated with poor clinical outcome in DIC
      patients.
AB  - We measured the plasma level of fibrinogen in 560 patients with disseminated
      intravascular coagulation (DIC) and evaluated its relationship with outcome and
      with other hemostatic markers. Forty-seven percent of patients had >200 mg/dL of
      plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that
      plasma fibrinogen level is not a sensitive marker for DIC. In our analysis of
      outcome and plasma fibrinogen levels, the rate of death was high in
      leukemia/lymphoma patients with high fibrinogen concentration, but no significant
      difference in outcome was observed in relation to plasma fibrinogen concentration
      in non-leukemia/lymphoma patients with DIC. Among patients with
      leukemia/lymphoma, the frequency of organ failure was markedly high in patients
      with high plasma levels of fibrinogen. Among patients without leukemia/lymphoma,
      the frequency of organ failure increased concomitantly with the increase in
      plasma fibrinogen levels. The international normalized ratio was significantly
      increased in leukemia/lymphoma patients with low fibrinogen. FDP levels were
      slightly increased in patients with low fibrinogen. Platelet count was
      significantly low in patients without leukemia/lymphoma with high fibrinogen. DIC
      score increased concomitantly with the reduction in plasma fibrinogen levels.
      Plasma levels of thrombomodulin and tissue factor were significantly high in
      patients with high fibrinogen levels. Plasma levels of antiplasmin and
      plasminogen were significantly decreased in patients with low fibrinogen. Plasma
      levels of plasmin plasmin-inhibitor complex and tissue type plasminogen
      activator/plasminogen activator inhibitor-1 complex (PAI-I) were significantly
      higher in patients with low fibrinogen than in those with high fibrinogen. Plasma
      levels of PAI-I and IL-6 were significantly higher in patients with high
      fibrinogen than in those with low fibrinogen. Patients with high fibrinogen
      levels showed less activation of secondary fibrinolysis, which might explain the
      occurrence of organ failure and poor outcome.

PMID- 12508261
TI  - Primary autoimmune myelofibrosis: definition of a distinct clinicopathologic
      syndrome.
AB  - Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with
      resulting features of myelophthisis. Besides hematopoietic malignancies and other
      neoplasms involving the bone marrow, myelofibrosis has been described in
      association with autoimmune disorders, especially systemic lupus erythematosus.
      We describe the clinicopathologic features of a primary form of autoimmune
      myelofibrosis (AIMF) in patients who do not have systemic lupus erythematosus or
      another well-defined autoimmune syndrome. Absence of marked splenomegaly,
      peripheral blood cytopenias with mild teardrop poikilocytosis and
      leukoerythroblastosis, bone marrow lymphoid aggregates, and presence of
      autoantibodies are some of the salient features of primary AIMF. AIMF should
      especially be differentiated from chronic idiopathic myelofibrosis, a neoplastic
      myeloproliferative disease. Primary AIMF appears to have an excellent prognosis,
      with all patients reported in this series responding to a short course of
      corticosteroid therapy.

PMID- 12508262
TI  - Use of oral mucosal neutrophil counts to detect the onset and resolution of
      profound neutropenia following high-dose myelosuppressive chemotherapy.
AB  - Severe neutropenia following cytotoxic, anti-cancer chemotherapy is well-known to
      be associated with an increased risk of infections that may be life-threatening,
      particularly if not treated immediately. Consequently, serial measurements of
      neutrophil counts in peripheral blood are done routinely following the
      administration of high-dose myelosuppressive chemotherapy in order to monitor the
      onset, severity, and duration of iatrogenic neutropenia. We have studied a non
      invasive method of quantifying neutrophils recoverable from the oral mucosa, a
      normal tissue site of neutrophil turnover, as an alternative approach for
      monitoring severe, chemotherapy-induced neutropenia. This method is based on the
      quantification of fluorochrome-stained neutrophils present in timed mouthwash
      specimens. Blood neutrophil (ANC) and mucosal neutrophil counts (MNC) were
      measured repeatedly in 23 patients who had been treated with dose-intensive
      chemotherapy for a variety of indications. All 23 patients developed profound
      neutropenia (ANC < 100/mm3), and 19 developed neutropenic fever (>101 degrees F)
      during the 2 weeks following treatment. Nadirs of neutropenia defined by MNC were
      significantly less prolonged than those defined by the ANC. Furthermore, the
      onset and resolution of neutropenic fever coincided more precisely with nadirs of
      neutropenia defined by the MNC than with those defined by the ANC. Our findings
      indicate that oral mucosal neutrophil counts predict the timing of clinical
      events associated with neutropenia (e.g., the onset and resolution of fever) with
      significantly greater accuracy than blood neutrophil counts.

PMID- 12508263
TI  - Acute myelogenous leukemia associated with extreme symptomatic thrombocytosis and
      chromosome 3q translocation: case report and review of literature.
AB  - Acute leukemias with thrombocytosis have been recently linked with structural
      abnormalities of the short arm of chromosome 3. A 46-year-old man with a 2-month
      history of recurrent transient ischemic attacks and abdominal pain developed an
      ischemic left foot and a gangrenous toe as his initial symptoms. Platelet count
      was 3.5 x 10(6)/microL, and despite plateletpheresis, the patient required left
      leg amputation. Pathologic examination was remarkable for arterial thrombosis in
      the absence of atherosclerotic lesions. A diagnosis of acute myeloid leukemia
      with a novel translocation between chromosomes 3q21, 16, and 7 was made.
      Induction therapy was unsuccessful, and the patient died of overwhelming sepsis
      within 5 weeks of diagnosis. The striking features of this case were extreme
      symptomatic thrombocytosis, peripheral gangrene without atherosclerosis, and a
      novel three-way chromosomal translocation involving chromosome 3q21.

PMID- 12508264
TI  - Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase
      chain reaction using bronchial lavage fluid.
AB  - Polymerase chain reaction (PCR) is a sensitive method for detection of
      Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to
      distinguish infection from contamination. We have established a technique to
      quantify Aspergillus DNA using a real-time PCR method to resolve this problem,
      and we report herein a successful application of real-time PCR to diagnose
      invasive pulmonary aspergillosis by comparing the amount of Aspergillus DNA in
      bronchial lavage fluid from an affected area to that from an unaffected area.
      This novel tool will provide rapid, sensitive, and specific diagnosis of
      pulmonary aspergillosis.

PMID- 12508265
TI  - Autoimmune hemolysis associated with primary biliary cirrhosis responding to
      ursodeoxycholic acid as sole treatment.
AB  - Coombs' positive autoimmune hemolytic anemia (AIHA) has been rarely described in
      association with primary biliary cirrhosis (PBC). The previously reported cases
      have responded to treatment with a combination of corticosteroids and
      ursodeoxycholic acid (UDCA). We report a case of AIHA occurring in association
      with PBC, which has responded to treatment with UDCA alone. Possible mechanisms
      of autoimmune hemolysis in this patient include bile salt induced immune
      dysregulation and direct damage to red cell membranes by bile salts leading to
      exposure of neoantigens and development of red cell autoantibodies. A trial of
      UDCA as a single agent should be considered as initial treatment in this rare
      disorder.

PMID- 12508267
TI  - Case of multiple myeloma mimicking an infectious disease with fever, intrahepatic
      cholestasis, renal failure, and pulmonary insufficiency.
AB  - We describe a case of multiple myeloma (MM) presenting with high fever,
      inflammatory chemistry abnormalities, simultaneous acute renal failure,
      cholestatic hepatitis, and acute lung failure. The extremely aggressive course
      and pulmonary involvement in the form of pulmonary alveolar proteinosis (PAP) are
      discussed, stressing the unusual nature of the findings and the variable picture
      of MM.

PMID- 12508266
TI  - Familial severe congenital neutropenia associated with infantile osteoporosis: a
      new entity.
AB  - A new entity manifested by severe congenital neutropenia associated with
      osteoporosis and recurrent bone fracture is described in a family. A possible
      role for a new recognized cytokine system involved in bone remodeling, the
      osteoprotegerin/receptor activator of nuclear factor-kappa B ligand, is
      suggested.

PMID- 12508268
TI  - Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis,
      and treatment.
AB  - The association between malignancy and clinical thrombosis has been recognized
      for nearly 140 years. The purpose of this review is to examine our current
      understanding of thrombosis as a complication of cancer and cancer therapy. The
      review includes a discussion of the epidemiology, pathophysiology, diagnosis and
      treatment.

PMID- 12508269
TI  - Childhood and adolescent large-cell lymphoma (LCL): a review of the Children's
      Cancer Group experience.
AB  - We reviewed the clinical characteristics, treatment, and outcome of 67 children
      with localized and 212 with disseminated large-cell lymphoma (LCL) treated during
      a 20-year period in 5 consecutive Children's Cancer Group (CCG) non-Hodgkin's
      lymphoma (NHL) trials. Clinical outcomes for patients treated on the four earlier
      studies with moderate-dose chemotherapy administered over 12-18 months were
      compared with patients treated most recently with short, intensive therapy.
      Median age at diagnosis was 12 years (range: 0-19 years). Male to female ratio
      was 1.8:1.0. Five-year event-free survival (EFS) was 92% +/- 3.3% and 50 +/- 3.5%
      for patients with localized LCL and disseminated LCL, respectively. After
      adjustment for lactate dehydrogenase (LDH), age at diagnosis, and BM involvement,
      short and intensive therapy as delivered on the most recent study, CCG-5911, was
      associated with an improved outcome (P< 0.05) compared to the four previous
      studies. Elevated LDH (> or = 500 IU/L) at diagnosis and young age (<5 years)
      were both significant independent predictors of poorer long-term EFS (P< 0.05).
      Long-term survival after relapse or other treatment failure was only 31% +/-
      4.7%. In summary, more recent shorter and intense therapy appears to be
      associated with superior event-free survival for children and adolescents with
      disseminated LCL. Large numbers of patients treated with shorter and intense
      therapy are required to confirm these preliminary observations.

PMID- 12508270
TI  - Novel beta-thalassemia trait (IVS I-1 G-->C) in a Japanese family.
AB  - A rare beta-thalassemia mutation at the splicing junction [namely, G-->C in
      intervening sequence (IVS) I-1] was found in a Japanese family. The proband and
      his mother were heterozygous for the mutation. Analysis of mRNA extracted from
      the reticulocyte-rich fraction obtained from the proband's mother revealed that
      the mutant beta-globin gene did not produce any detectable, stable mRNA including
      exon 1 and exon 2, since the polymorphism in exon 1 on her mutant gene was not
      detected in the RT-PCR products.

PMID- 12508271
TI  - Cyclosporin A induces erythroid differentiation of K562 cells through p38 MAPK
      and ERK pathways.
AB  - We studied the effects of cyclosporin A (CsA) on the erythroid differentiation of
      human erythroid leukemia cell line K562. After K562 was treated with CsA for 4
      days, the percentage of hemoglobinized cells was increased by 3.3 times. Because
      it was reported p38 MAPK (p38) and ERK are involved in erythropoietin-induced
      erythroid differentiation, we studied their roles using specific inhibitors. p38
      inhibitor (SB203580) prevented CsA-induced hemoglobin synthesis in K562 cells,
      although MEK/ERK inhibitor (U0126) enhanced it by 3.3 times in K562 cells. These
      results indicate activation of p38 and inactivation of ERK are involved in CsA
      induced erythroid differentiation of K562 cells.

PMID- 12508272
TI  - HHV8-related non-Hodgkin's lymphoma of the spermatic cord in a patient with HIV
      associated multicentric Castleman disease.

PMID- 12508273
TI  - Combination therapy of DDAVP and conjugated estrogens for a recurrent large
      subcutaneous hematoma in Ehlers-Danlos syndrome.

PMID- 12508274
TI  - Masters change, slaves remain.
AB  - Sex determination offers an opportunity to address many classic questions of
      developmental biology. In addition, because sex determination evolves rapidly, it
      offers an opportunity to investigate the evolution of genetic hierarchies. Sex
      determination in Drosophila melanogaster is controlled by the master regulatory
      gene, Sex lethal (Sxl). DmSxl controls the alternative splicing of a downstream
      gene, transformer (tra), which acts with tra2 to control alternative splicing of
      doublesex (dsx). DmSxl also controls its own splicing, creating an autoregulatory
      feedback loop that ensures expression of Sxl in females, but not males. A recent
      paper has shown that in the dipteran Ceratitis capitata later (downstream) steps
      in the regulatory hierarchy are conserved, while earlier (upstream) steps are
      not. Cctra is regulated by alternative splicing and apparently controls the
      alternative splicing of Ccdsx. However, Cctra is not regulated by CcSxl. Instead
      it appears to autoregulate in a manner similar to the autoregulation seen with
      DmSxl.

PMID- 12508275
TI  - Size isn't everything.
AB  - Much progress has been made recently towards uncovering the mechanisms that
      control the size to which organisms and their organs grow, and identifying some
      of the genes responsible. Size control, however, is only half of the equation. In
      growing to the right size, tissues must also grow to the right shape. A recent
      paper suggests that a hitherto overlooked cellular behaviour governs the size and
      shape of a growing tissue, and issues a challenge to developmental biologists to
      identify the molecular mechanisms involved.

PMID- 12508276
TI  - CtBP family proteins: more than transcriptional corepressors.
AB  - CtBP family proteins predominantly function as transcriptional corepressors.
      Studies with mutant mouse suggest that the two mouse genes, Ctbp1 and Ctbp2, play
      unique and redundant gene regulatory roles during development.1 Ctbp1-deficient
      mice are viable, but are small and die early, while Ctbp2 deficiency leads to
      embryonic lethality. Ctbp2-null mutation causes defects in axial patterning,
      heart morphogenesis and neural development. The Ctbp2 mutant phenotype is more
      severe in the absence of Ctbp1. The studies with Ctbp2 mutant embryos suggest
      that CtBP can also activate transcription. A plant CtBP homolog, Angustifolia
      (AN), has recently been identified.2,3 AN controls polar elongation of leaf cells
      via the microtubule cytoskeleton. Microarray analysis suggests that AN also
      functions as a transcriptional repressor. Thus, the CtBP family proteins control
      cellular processes by serving as transcriptional activators and regulators of the
      cytoskeleton as well as transcriptional corepressors.

PMID- 12508277
TI  - How the community effect orchestrates muscle differentiation.
AB  - The "community effect" is necessary for tissue differentiation. In the Xenopus
      muscle paradigm, e-FGF has been identified as a candidate community factor.
      Standley et al.1 now show that the community effect, mediated through FGF
      signalling, continues to be important at later stages of development in the
      posterior part of the embryo. In this region, the paraxial mesoderm is still
      undergoing segmentation into somites, which are the site of early skeletal muscle
      formation. Indeed, somitogenesis, together with the read-out of the Hox code,
      which confers anteroposterior positional identity, is regulated by FGF
      signalling. This raises the question of the co-ordination between these events
      and the community effect which orchestrates myogenesis.

PMID- 12508278
TI  - Activation of the JNK signaling pathway: breaking the brake on apoptosis.
AB  - The JNK signaling pathway is involved in regulation of many cellular events,
      including growth control, transformation and programmed cell death (apoptosis).
      The role of JNK activation in apoptosis is highly controversial, being suggested
      to have a pro-apoptotic, anti-apoptotic or no role in this process. It appears
      that the JNK pathway functions in a cell-type and stimulus-dependent manner and
      its different components can sometimes play opposing roles in apoptosis. Recent
      studies reveal that the effect of JNK activation on apoptosis depends on the
      activity of other signaling pathways like the NF-kappaB pathway. Here we propose
      a model that can explain how activation of the JNK pathway "breaks the brake" on
      apoptosis, thereby regulating, but not initiating the apoptotic process.

PMID- 12508279
TI  - Localizing synaptic mRNAs at the neuromuscular junction: it takes more than
      transcription.
AB  - The neuromuscular junction has been used for several decades as an excellent
      model system to examine the cellular and molecular events involved in the
      formation and maintenance of a differentiated chemical synapse. In this context,
      several laboratories have focused their efforts over the last 15 years on the
      important contribution of transcriptional mechanisms to the regulation of the
      development and plasticity of the postsynaptic apparatus in muscle fibers.
      Converging lines of evidence now indicate that post-transcriptional events,
      operating at the level of mRNA stability and targeting, are likely to also play
      key roles at the neuromuscular junction. Here, we present the recent findings
      highlighting the role of these additional molecular events and extend our review
      to include data showing that post-transcriptional events are also important in
      the control of the expression of genes encoding synaptic proteins in muscle cells
      placed under different conditions. Finally, we discuss the possibility that mis
      regulation of post-transcriptional events can occur in certain neuromuscular
      diseases and cause abnormalities of the neuromuscular junction.

PMID- 12508280
TI  - Movement through Slits: cellular migration via the Slit family.
AB  - First isolated in the fly and now characterised in vertebrates, the Slit proteins
      have emerged as pivotal components controlling the guidance of axonal growth
      cones and the directional migration of neuronal precursors. As well as extensive
      expression during development of the central nervous system (CNS), the Slit
      proteins exhibit a striking array of expression sites in non-neuronal tissues,
      including the urogenital system, limb primordia and developing eye. Zebrafish
      Slit has been shown to mediate mesodermal migration during gastrulation, while
      Drosophila slit guides the migration of mesodermal cells during myogenesis. This
      suggests that the actions of these secreted molecules are not simply confined to
      the sphere of CNS development, but rather act in a more general fashion during
      development and throughout the lifetime of an organism. This review focuses on
      the non-neuronal activities of Slit proteins, highlighting a common role for the
      Slit family in cellular migration.

PMID- 12508281
TI  - Constitutive cycling: a general mechanism to regulate cell surface proteins.
AB  - Cells can change their function by rapidly modulating the levels of certain
      proteins at the plasma membrane. This rapid modulation is achieved by using a
      specialised trafficking process called constitutive cycling. The constitutive
      cycling of a variety of transmembrane proteins such as receptors, channels and
      transporters has recently been directly demonstrated in a wide range of cell
      types. This regulation is thought to underlie important biological phenomena such
      as learning and memory, gastric acid secretion and water and blood glucose
      homeostasis. This review discusses the molecular mechanisms of constitutive
      cycling, its regulation by extracellular agents such as hormones and its
      misregulation in disease states.

PMID- 12508282
TI  - Multiple mediators of plant programmed cell death: interplay of conserved cell
      death mechanisms and plant-specific regulators.
AB  - Programmed cell death (PCD) is a process aimed at the removal of redundant,
      misplaced, or damaged cells and it is essential to the development and
      maintenance of multicellular organisms. In contrast to the relatively well
      described cell death pathway in animals, often referred to as apoptosis,
      mechanisms and regulation of plant PCD are still ill-defined. Several
      morphological and biochemical similarities between apoptosis and plant PCD have
      been described, including DNA laddering, caspase-like proteolytic activity, and
      cytochrome c release from mitochondria. Reactive oxygen species (ROS) have
      emerged as important signals in the activation of plant PCD. In addition, several
      plant hormones may exert their respective effects on plant PCD through the
      regulation of ROS accumulation. The possible plant PCD regulators discussed in
      this review are integrated in a model that combines plant-specific regulators
      with mechanisms functionally conserved between animals and plants.

PMID- 12508283
TI  - The viral control of cellular acetylation signaling.
AB  - It is becoming clear that the post-translational modification of histone and non
      histone proteins by acetylation is part of an important cellular signaling
      process controlling a wide variety of functions in both the nucleus and the
      cytoplasm. Recent investigations designate this signaling pathway as one of the
      primary targets of viral proteins after infection. Indeed, specific viral
      proteins have acquired the capacity to interact with cellular acetyltransferases
      (HATs) and deacetylases (HDACs) and consequently to disrupt normal acetylation
      signaling pathways, thereby affecting viral and cellular gene expression. Here we
      review the targeting of cellular HATs and HDACs by viral proteins and highlight
      different strategies adopted by viruses to control cellular acetylation signaling
      and to accomplish their life cycle.

PMID- 12508284
TI  - Cell signaling through membrane mucins.
AB  - MUC1 and MUC4 are the two membrane mucins that have been best characterized.
      Although they have superficially similar structures and have both been shown to
      provide steric protection of epithelial surfaces, recent studies have also
      implicated them in cellular signaling. They act by substantially different
      mechanisms, MUC4 as a receptor ligand and MUC1 as a docking protein for signaling
      molecules. MUC4 is a novel intramembrane ligand for the receptor tyrosine kinase
      ErbB2/HER2/Neu, triggering a specific phosphorylation of the ErbB2 in the absence
      of other ErbB ligands and potentiating phosphorylation and signaling through the
      ErbB2/ErbB3 heterodimeric receptor complex formed in the presence of neuregulin.
      In contrast, MUC1 has a highly conserved cytoplasmic tail, which binds beta
      catenin, a key component of adherens junctions and a regulator of transcription,
      in a process that is tightly regulated by MUC1 phosphorylation. The specific
      localization of these membrane mucins to the apical surfaces of epithelial cells
      suggests that their signaling functions may be important as sensor mechanisms in
      response to invasion or damage of epithelia.

PMID- 12508285
TI  - Outsourcing in the brain: do neurons depend on cholesterol delivery by
      astrocytes?
AB  - Brain function depends on the cooperation between highly specialized cells.
      Neurons generate electrical signals and glial cells provide structural and
      metabolic support. Here, I propose a new kind of job-sharing between neurons and
      astrocytes. Recent studies on primary cultures of highly purified neurons from
      the rodent central nervous system (CNS) suggest that, during development, neurons
      reduce or even abandon cholesterol synthesis to save energy and import
      cholesterol from astrocytes via lipoproteins. The cholesterol shuttle may be
      restricted to compartments distant from the soma including synapses and may be
      regulated by electrical activity. Testing these hypotheses will help to improve
      our still insufficient understanding of brain cholesterol metabolism and its role
      in neurodegeneration.

PMID- 12508286
TI  - Making use of the primary tumour.
AB  - Surgical resection of a primary tumour is often not sufficient to cure a patient.
      Even when no residual cancer can be detected at time of surgery, metastases may
      appear in the following years, which indicates that the primary tumour had
      apparently spread before surgery. Following surgery, systemic chemotherapy may be
      used to eradicate micro-metastatic disease. Here we present two unconventional
      strategies that implement new insights into tumour biology and tumour immunology
      in the treatment of patients with cancer. Both experimental strategies use the
      individual characteristics of the patient's primary tumour to optimise the
      control of life-threatening micro-metastases. We aim to modulate the patient's
      adaptive immune system, targeting it towards the patient's own tumour cells to
      eradicate residual disease following local treatment. In one approach, this is
      done by autologous tumour cell vaccinations as adjuvant treatment for colon
      cancer patients and, in a second approach, by giving chemo-immunotherapy before
      local treatment to women with locally advanced breast cancer.

PMID- 12508287
TI  - Fly developments: an introspective.

PMID- 12508288
TI  - A public debate about the feasibility of reversing human ageing could be
      detrimental.

PMID- 12508290
TI  - Congenital myasthenic syndromes: progress over the past decade.
AB  - Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic
      basal lamina, and postsynaptic proteins. The presynaptic CMS are associated with
      defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh
      resynthesis. Defects in ACh resynthesis have now been traced to mutations in
      choline acetyltransferase. A basal lamina CMS is caused by mutations in the
      collagenic tail subunit (ColQ) of the endplate species of acetylcholinesterase
      that prevent the tail subunit from associating with catalytic subunits or from
      becoming inserted into the synaptic basal lamina. Most postsynaptic CMS are
      caused by mutations in subunits of the acetylcholine receptor (AChR) that alter
      the kinetic properties or decrease the expression of AChR. The kinetic mutations
      increase or decrease the synaptic response to ACh and result in slow- and fast
      channel syndromes, respectively. Most low-expressor mutations reside in the AChR
      epsilon subunit and are partially compensated by residual expression of the fetal
      type gamma subunit. In a subset of CMS patients, endplate AChR deficiency is
      caused by mutations in rapsyn, a molecule that plays a critical role in
      concentrating AChR in the postsynaptic membrane.

PMID- 12508291
TI  - Sonography in the diagnosis of carpal tunnel syndrome: a critical review of the
      literature.
AB  - Advances in ultrasound technology have made it possible to gain higher spatial
      resolution and even depict nerves with excellent visual quality. In this article,
      the literature concerning sonography in the diagnosis of carpal tunnel syndrome
      (CTS) is critically reviewed. We searched Medline for studies on sonography in
      the diagnosis of CTS and used the reference lists of the articles found. A total
      of seven studies on the diagnostic capabilities of sonography was found. There
      were considerable differences in study design. A reliable diagnosis of CTS could
      be made sonographically, mainly based on an increase in cross-sectional area of
      the median nerve at the level of the pisiform or hamate bone. However, most
      studies could not compare the diagnostic capabilities of sonography to those of
      electrodiagnostic studies, because the latter was applied as the gold standard.
      Several other reports on the possible extra value of sonography in CTS are
      mentioned (mass lesions, anatomical variants, rheumatological diseases, renal
      dialysis-related amyloidosis, surgery, corticosteroid injection). It is probable
      that sonography will not replace electrodiagnostic studies, but may serve as an
      additional investigation. To gain further insight into the possible additional
      value of sonography, it is necessary to examine subcategories of CTS patients in
      which electrodiagnostic studies are equivocal.

PMID- 12508292
TI  - Initial semeiology in children with Charcot-Marie-Tooth disease 1A duplication.
AB  - The aim of this study was to describe the initial signs and symptoms in Charcot
      Marie-Tooth disease type 1A (CMT-1A). Twelve secondary cases with CMT-1A were
      serially evaluated. Ages at initial clinical examination ranged between 1 month
      and 5 years (mean, 2 years) and final ages between 6 and 23 years (mean, 13
      years). First signs of the disease were detected at initial or upon serial
      examinations in all 12 patients at ages ranging between 1 and 10 years (median, 4
      years). The most frequent signs were lower limb areflexia in 12, difficulty in
      heel walking in 8, nerve enlargement in 6, atrophy of intrinsic foot muscles in
      6, clawing of toes in 5, pes cavus or cavus varus in 4, shortening of Achilles
      tendon in 3, peroneal weakness in 1, and stocking hypoesthesia in 1. Only three
      patients were symptomatic at the initial evaluation. We conclude that initial CMT
      1A signs usually appear in early childhood, although they may be quite subtle and
      require serial examinations for detection. Lower limb areflexia is the only
      constant early sign.

PMID- 12508293
TI  - Predictability of maximum voluntary isometric knee extension force from
      submaximal contractions in older adults.
AB  - The purposes of this study were to develop and test a model describing the
      relationship between the central activation ratio (CAR; a measure of voluntary
      muscle activation) and percent maximum voluntary contraction (%MVC) force for old
      adults and to provide a method for more accurate determination of voluntary
      muscle activation failure. Twenty-one adults (ages 64-81) performed isometric
      testing of the quadriceps at 25%, 50%, 75%, and 100% MVC. During each
      contraction, a 100-HZ, 120-ms train of electrical pulses was delivered to the
      quadriceps muscle to quantify voluntary muscle activation. Similar to a young,
      healthy population (ages 20-35), a curvilinear relationship existed between the
      CAR and %MVC force for older adults. Predictions of subjects' MVCs using the
      linear model of CAR-%MVC force relationship generally demonstrated poor agreement
      with actual MVCs. Predictions of MVC from submaximal contractions (25%, 50%, and
      75%) using a previously identified curvilinear young adult CAR-%MVC relationship
      were good [ICC (2,1): 0.81, 0.96, and 0.82, respectively]. Similar agreement was
      obtained from the curvilinear older adult CAR-%MVC relationship. These data
      suggest that the CAR-%MVC relationship is similar in young and older adult
      subjects and that curvilinear models of this relationship can predict MVC forces
      in older adults more accurately. Reexamination of the relationship between the
      CAR and %MVC force may allow a more accurate determination of how failure of
      voluntary muscle activation contributes to weakness in old adults.

PMID- 12508294
TI  - The utility of segmental nerve conduction studies in ulnar mononeuropathy at the
      elbow.
AB  - Patients with clinical evidence of ulnar mononeuropathy at the elbow may have
      normal routine motor and sensory nerve conduction studies, suggesting a low
      sensitivity for these methods. Other, more specialized techniques may have a
      higher sensitivity, increasing diagnostic yield, and provide more specific
      localization of the lesion. We compared the sensitivity and specificity of ulnar
      segmental nerve conduction studies (SgNCS or "inching") at 2-cm intervals with
      those of routine ulnar motor and sensory studies. We studied 21 arms with
      symptoms or signs of ulnar neuropathy and 25 asymptomatic control arms. SgNCS
      proved significantly more sensitive than more routine studies in diagnosing ulnar
      neuropathy at the elbow, with a sensitivity of 81%, whereas motor conduction
      velocity in a longer (10-14 cm) segment across the elbow was the next most
      sensitive at 24%. Recording from the first dorsal interosseous muscle did not
      improve sensitivity when compared with recording from the abductor digiti quinti.
      Short SgNCS significantly improves detection of ulnar mononeuropathy at the elbow
      and should be considered when routine studies are negative and clinical suspicion
      remains high.

PMID- 12508295
TI  - Expression of matrix metalloproteinases, inhibitor, and acid phosphatase in
      muscles of immobilized hindlimbs of rats.
AB  - External fixation procedures of limb immobilization provide excellent
      experimental models to study mechanisms involved in muscle disuse atrophy and
      recovery. Female Wistar rats (7-8 months old) had their right hindlimbs
      immobilized by an external fixation procedure for 5, 10, 21, and 30 days. Muscle
      mass of the gastrocnemius and quadriceps muscles was reduced by 41-46% in
      comparison with contralateral nonimmobilized legs. Acid phosphatase activities
      were significantly increased after 21 and 30 days of hindlimb immobilization.
      Histochemical staining for acid phosphatase activities increased in myofibers
      after the external fixation and also in macrophages in the adjacent extracellular
      matrix. Matrix metalloproteinase (MMP-2 and MMP-9) activities assessed by gel
      zymography and also a tissue inhibitor of metalloproteinases (TIMP-1) assessed by
      Western blot were elevated in the immobilized hindlimb muscles. Our study
      demonstrated that metalloproteinases are expressed relatively late after limb
      immobilization and appear to be responsible to a large degree for degradation of
      the extracellular matrix in experimental disuse atrophy.

PMID- 12508296
TI  - Comparison of surgical and electrodiagnostic findings in single root lumbosacral
      radiculopathies.
AB  - To identify the segmental innervation of L-2-S-1 muscles, we compared the
      preoperative electrodiagnostic examinations of 45 patients with single-level
      lumbosacral radiculopathies confirmed radiologically and surgically. The
      electrodiagnostic findings were classified as abnormal only by the needle
      examination and only if muscles demonstrated active denervation or a marked
      neurogenic motor unit potential firing pattern. In comparison to other surgical,
      intraoperative root stimulation, and clinical studies, we found several
      differences. Overall, there was little overlap among L-2-4, L-5, and S-1
      radiculopathies. The tibialis anterior was predominantly L-5 innervated, the
      gastrocnemius (medial and lateral head) predominantly S-1 innervated, and the
      biceps femoris (short and long head) exclusively S-1 innervated. The two heads of
      biceps femoris were not affected in any patients with L-5 radiculopathy in whom
      they were examined. These findings help guide both the clinician and surgeon in
      the diagnosis and treatment of lumbosacral radiculopathies.

PMID- 12508297
TI  - Attenuation of stretch-induced histopathologic changes of skeletal muscles by
      quinacrine.
AB  - Quinacrine is an inhibitor of phospholipase A(2), an enzyme thought to be
      involved in activity-related injury of skeletal muscles. Histopathologic changes
      after injury by stretches of activated plantar-flexor muscles were measured in
      untreated and quinacrine-treated rats. On day 4 of treatment (50 mg.kg(-1)
      intraperitoneally for 5 days), 30 stretches were induced by ankle rotation after
      muscles reached a maximal isometric force. During the stretch protocol, peak
      stretch forces and isometric force deficits after each stretch [total deficits
      56.7 +/- 2.8% (untreated rats) and 59.6 +/- 1.7% (quinacrine-treated rats)] were
      similar for both groups (n = 6 each). Two days after the stretch protocol,
      histopathologic changes were evaluated using antibody staining on cross-sections
      of gastrocnemius medialis muscles. Swollen myofibers devoid of desmin were
      identified. Similar cells, but not all swollen myofibers, in adjacent sections
      stained for albumin. Quinacrine reduced the number of desmin-negative and albumin
      positive cells by 88% (P < 0.05) and 84% (P < 0.05), indicating that it
      attenuated histopathologic changes that follow stretch injury of activated
      skeletal muscles. Histopathologic changes following muscle injury or myopathic
      disease may thus be reduced or even prevented by selective drug intervention,
      thereby reducing the risk of muscle fibrosis. Muscle Nerve 27: 65-71, 2003

PMID- 12508298
TI  - Effect of training on contractile and metabolic properties of wrist extensors in
      spinal cord-injured individuals.
AB  - Paretic human muscle rapidly loses strength and oxidative endurance, and
      electrical stimulation training may partly reverse this. We evaluated the effects
      of two training protocols on the contractile and metabolic properties of the
      wrist extensor in 12 C-5/6 tetraplegic individuals. The wrist extensor muscles
      were stimulated for 30 min/day, 5 days/week, for 12 weeks, using either a high
      resistance (Hr) or a low-resistance (Lr) protocol. Total work output was similar
      in both protocols. The nontrained arm was used as a control. Maximum voluntary
      torque increased in the Hr (P < 0.05) but not the Lr group. Electrically
      stimulated peak tetanic torque at 15 HZ, 30 HZ, and 50 HZ were unchanged in the
      Lr group and tended to increase only at 15 HZ (P < 0.1) in the Hr group.
      Resistance to fatigue, however, increased (P < 0.05) in both Hr (42%) and Lr
      (41%) groups. Muscle metabolism was evaluated by (31)P nuclear magnetic resonance
      spectroscopy ((31)P-NMRS) during and following a continuous 40-s 10-HZ
      contraction. In the Hr group the cost of contraction decreased by 38% (P < 0.05)
      and the half-time of phosphocreatine (PCr) recovery was shortened by 52% (P <
      0.05). Thus, long-term electrically induced stimulation of the wrist extensor
      muscles in spinal cord injury (SCI) increases fatigue resistance independent of
      training pattern. However, only the Hr protocol increased muscle strength and was
      shown to improve muscle aerobic metabolism after training. Muscle Nerve 27: 72
      80, 2003

PMID- 12508299
TI  - Ryanodine receptor antibodies in myasthenia gravis: epitope mapping and effect on
      calcium release in vitro.
AB  - Patients with myasthenia gravis can have antibodies against skeletal muscle
      ryanodine receptor (Ry1), the sarcoplasmic reticulum calcium-release channel,
      which plays a crucial role in excitation-contraction coupling. We have screened a
      panel of overlapping Ry1 fusion proteins with Ry1 antibody-containing myasthenia
      gravis sera to identify the main immunogenic region. The pc2 Ry1 fusion protein
      representing a Ry1 region close to the N-terminus (residues 799-1172) was
      identified as the main immunogenic region for the antibodies. The binding
      kinetics of the Ry1 antibodies to the pc2 Ry1 fusion protein were tested using an
      optical biosensor. Ry1 antibodies in the IgG fraction from sera of patients with
      myasthenia gravis bound with high affinity and with a stoichiometry of 1:1. The
      functional effect of these Ry1 antibodies was tested in an in vitro Ca2+-release
      assay. The Ry1 antibodies induced a twofold increase of the half-maximal
      concentration for 4-Cl-m-cresol-induced Ca2+ release from terminal cisternae
      vesicles but had no effect on V(max). The effect on 4-Cl-m-cresol-induced Ca2+
      release was specific, as preincubation of the active IgG fraction with the pc2
      Ry1 fusion protein abolished the inhibition. These data suggest that the Ry1
      sequence defined by residues 799-1172 is involved in the regulation of Ry1
      function, and that this regulation could be functionally affected in vivo in
      patients with myasthenia gravis.

PMID- 12508300
TI  - Effects of superimposed electrical stimulation on perceived discomfort and torque
      increment size and variability.
AB  - Superimposed electrical stimulation techniques can be used to detect central
      activation failure (CAF), that is, incomplete central nervous system recruitment
      or suboptimal activation of motor units. The purpose of this study was to
      evaluate the effects of two stimulation parameters on perceived discomfort and
      torque increment size and variability. Discomfort was evaluated using a visual
      analog scale (0-100 mm) for pain. The rectus femoris muscle of the dominant leg
      of 24 young healthy men was stimulated during submaximal (80% maximal) voluntary
      contractions. The size and variability of torque increments and perceived
      discomfort were assessed following stimulation with: (1) pulse trains (100 HZ,
      150 V, 0.2-ms pulse duration) of different lengths (50 ms and 100 ms); and (2)
      pulse trains (100 HZ, 100 ms, 150 V) with different pulse durations (0.2 ms and
      0.1 ms). Pulse trains of 100 ms generated larger torque increments and produced
      less variability, but caused more discomfort than pulse trains of 50 ms. Average
      discomfort ratings for pulse trains of 100 ms were 43.1 mm, and of 50 ms were
      53.2 mm. There was no difference in torque increment size or in variability
      between pulse trains with pulse durations of 0.1 ms and 0.2 ms, whereas
      discomfort was less for the shorter pulse durations; average discomfort ratings
      were 53.1 mm and 58.1 mm for pulse durations of 0.1 ms and 0.2 ms, respectively.
      Thus, the appropriate selection of stimulation parameters can reduce discomfort
      but maintain the ability to detect CAF.

PMID- 12508301
TI  - Are voluntary muscle activation deficits in older adults meaningful?
AB  - The relationship between the central activation ratio (CAR) and contraction force
      is curvilinear, not linear as was previously believed. Voluntary quadriceps
      femoris muscle activation from previously collected data sets in 46 older adults
      (64-84 years) and 46 young adults (18-32 years) were therefore reexamined using a
      curvilinear model of the voluntary muscle activation-percent maximum voluntary
      force relationship. This method revealed lower voluntary muscle activation in
      older adults (0.868 +/- 0.018) than younger subjects (0.978 +/- 0.005). The mean
      difference between older and younger adults was 11%, which may be more meaningful
      than previous reports of 2-4% because it could explain the greater rate of
      strength loss as compared to loss of muscle mass as humans age.

PMID- 12508302
TI  - Viral RNA in nerve tissues of patients with hepatitis C infection and peripheral
      neuropathy.
AB  - To assess the presence of viral ribonucleic acid (RNA) in nerve tissues of 15
      patients with hepatitis C virus (HCV) infection and peripheral neuropathy with
      (11) or without (4) mixed cryoglobulinemia, nested reverse transcription
      polymerase chain reaction (RT-PCR) was performed. Amplification of HCV-RNA was
      successful in 7 patients with and 3 without mixed cryoglobulinemia. This study
      demonstrates that the nested RT-PCR technique is a sensitive method to detect
      viral RNA in nerve tissue, and offers further evidence that in patients with HCV
      infection peripheral neuropathy can occur in the absence of mixed
      cryoglobulinemia.

PMID- 12508303
TI  - Two novel mutations in the myophosphorylase gene in a patient with McArdle
      disease.
AB  - We identified two novel mutations in exon 2 of the myophosphorylase gene in a 33
      year-old German women with McArdle disease. The patient was compound heterozygous
      for a novel nonsense mutation at codon 84 changing tyrosine to stop codon (Y84X)
      and for a novel missense mutation at codon 93 changing arginine to tryptophan
      (R93W). These mutations are the first to be described in exon 2 and expand the
      genetic heterogeneity in patients with McArdle disease.

PMID- 12508304
TI  - Depression of spinal motoneurons may underlie weakness associated with severe
      anemia.
AB  - A 37-year-old woman had a 2-week history of progressive weakness, muscle
      hypotonia, and absent or hypoactive deep tendon reflexes. Nerve conduction
      studies showed diminished H-reflexes and absent or decreased persistence of F
      waves in all limbs. The patient was admitted to the hospital with a diagnosis of
      Guillain-Barre syndrome. Laboratory studies revealed severe anemia with a
      hemoglobin level of 4.1 g/dl and hematocrit of 15.1%. Immediate blood transfusion
      resulted in a hemoglobin of 13.2 g/dl and hematocrit of 40.2%, associated with
      rapid neurological recovery (normal stretch reflexes and muscle strength) and
      normalization of F-waves and H-reflexes. This case demonstrates that severe
      anemia may be associated with signs and symptoms that mimic Guillain-Barre
      syndrome, both clinically and electrophysiologically. It also suggests that a
      relative depression of spinal motoneuron excitability may be a possible mechanism
      for the weakness that is commonly observed in severe anemia.

PMID- 12508305
TI  - Leukocytoclastic-vasculitic neuropathy associated with chronic Epstein-Barr virus
      infection.
AB  - We report a patient with leukocytoclastic-vasculitic neuropathy associated with
      chronic Epstein-Barr virus (EBV) infection. A 55-year-old man had been suffering
      from chronic progressive axonal polyneuropathy and skin erythema for 3 years. A
      skin biopsy showed capillary vasculitis with clustered leukocyte fragments.
      Findings of serum assays, a polymerase chain reaction for EBV-DNA, and in situ
      hybridization indicated chronic EBV infection. Immunosuppressive treatment
      resulted in the gradual lessening of his general and neurologic symptoms.

PMID- 12508306
TI  - Consensus criteria for the diagnosis of multifocal motor neuropathy.
AB  - At this time, there are no widely accepted criteria for the diagnosis of
      multifocal motor neuropathy. Furthermore, there is insufficient empirical data to
      define clinical and laboratory features that may reliably separate certain lower
      motor neuron syndromes with overlapping features as distinct. The AAEM therefore
      developed five criteria through a formal consensus process that are described in
      this document to act as a guide for diagnosing multifocal motor neuropathy with a
      high level of confidence (definite multifocal motor neuropathy) or with a
      moderate level of confidence (probable motor neuropathy). In brief, the diagnosis
      requires clinical weakness without objective sensory loss or upper motor neuron
      signs in the distribution of two or more named nerves that is due to conduction
      block in two or more motor nerves outside of common entrapment sites.
      Furthermore, normal results are required for sensory nerve conduction studies.

PMID- 12508307
TI  - Reliability of an electrical method to induce muscle cramp.

PMID- 12508309
TI  - Acquisition of neuronal and glial markers by neural crest-derived cells in the
      mouse intestine.
AB  - Enteric neurons and glia arise from the neural crest. The phenotype of crest
      derived cells was examined as they differentiated into neurons or glia in the
      mouse small and large intestine. Previous studies have shown that
      undifferentiated enteric crest-derived cells are
      Phox2b(+)/Ret(+)/p75(+)/Sox10(+), and at embryonic day (E) 10.5, about 10-15% of
      the crest-derived cells in the small intestine have started to differentiate into
      neurons. In the current study, by E12.5 and E14.5, about 25% and 47%,
      respectively, of Phox2b(+) cells in the small intestine were immunoreactive to
      the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did
      not change dramatically from E14.5 onward. The differentiation of crest-derived
      cells into neurons in the colon lagged behind that in the small intestine by
      several days. Differentiating enteric neurons showed high Ret, low p75, and
      undetectable Sox10 immunostaining. Glial precursors were identified by the
      presence of brain-specific fatty acid binding protein (B-FABP) and detected first
      in the fore- and rostral midgut at E11.5. Glial precursors appeared to be B
      FABP(+)/Sox10(+)/p75(+) but showed low Ret immunostaining. S100b was not detected
      until E14.5. Adult glial cells were B-FABP(+)/Sox10(+)/p75(+)/S100b(+). A nucleic
      acid stain (to identify all ganglion cells) was combined with immunostaining for
      PGP9.5 and S100b to detect neurons and glial cells, respectively, in the
      postnatal intestine. At postnatal day 0, fewer than 5% and 10% of cells in
      myenteric ganglia of the small and large intestine, respectively, were neither
      PGP9.5(+) nor S100b(+). Because some classes of neurons are not present in
      significant numbers until after birth, the expression of PGP9.5 by developing
      enteric neurons appeared to precede the expression of neuron type-specific
      markers.

PMID- 12508310
TI  - Neurochemical comparison of synaptic arrangements of parvocellular,
      magnocellular, and koniocellular geniculate pathways in owl monkey (Aotus
      trivirgatus) visual cortex.
AB  - As in other primates, the lateral geniculate nucleus (LGN) of owl monkeys
      contains three anatomically and physiologically distinct relay cell classes, the
      magnocellular (M), parvocellular (P), and koniocellular (K) cells. M and P LGN
      cells send axons to the upper and lower tiers of layer IV, and K cells send axons
      to the cytochrome oxidase (CO) blobs of layer III and to layer I of primary
      visual cortex (V1). Our objective was to compare the synaptic arrangements made
      by these axon classes. M, P, and K axons were labeled in adult owl monkeys by
      means of injections of wheat germ agglutinin-horseradish peroxidase into the
      appropriate LGN layers. The neurochemical content of both pre- and postsynaptic
      profiles were identified by postembedding immunocytochemistry for gamma
      aminobutyric acid (GABA) and glutamate. Our key finding is that the synaptic
      arrangements made by M, P, and K axons in owl monkey exhibit more similarities
      than differences. They are exclusively presynaptic, contain glutamate and form
      asymmetric synapses mainly with glutamate-positive dendritic spines. The majority
      of the remaining axons synapse with glutamatergic dendritic shafts. There are
      also differences between LGN pathways. M and P terminals are significantly larger
      and more likely to make multiple synapses than K axons, although M and P axons do
      not differ from each other in either of these characteristics. Of interest, a
      larger percentage of M and K axons than P axons make synapses with GABAergic
      dendritic shafts. Cells directly postsynaptic to M and K axons are known to
      exhibit orientation selectivity and, in some cases, direction selectivity. Cells
      postsynaptic to P axons do not show these properties, but instead tend to reflect
      their LGN inputs more faithfully; therefore, it is possible that these
      physiologic differences seen in the cortical cells postsynaptic to different LGN
      pathways reflect the differential involvement of inhibitory circuits.

PMID- 12508311
TI  - Ontogeny of calcitonin receptor mRNA and protein in the developing central
      nervous system of the rat.
AB  - In this study, the expression of receptors for calcitonin (CTR), the CTR C1a and
      C1b isoforms, was investigated during development of the fetal rat central
      nervous system (CNS) by using in situ hybridization and immunohistochemistry.
      Coincident expression with both techniques was evident. Immunohistochemical
      evidence for the expression of the C1a isoform alone was found. Expression was
      first observed at embryonic day 12/13 (E12/E13) within and adjacent to the
      ventricular zones known to include primary matrices of proliferation, in regions
      of the preoptic area, anterior and posterior hypothalamus, anterior and posterior
      pons, medulla, and spinal cord. At later times, with the decline in the density
      of immunoreactivity at these loci (E15), expression in primary matrices was found
      later at distinct loci within the ventricular zones of cerebellum (E17), and at
      E19, the tectum, lateral ventricle, and cortical subplate. By E19, the density of
      staining had increased and was widespread throughout the expanding CNS. In the
      rostral domains, moderate to high density was found in the external plexiform
      layer; the medial preoptic area and nucleus; the ventromedial, dorsomedial, and
      arcuate hypothalamic nuclei; and the lateral and posterior hypothalamic areas. In
      the midbrain, similar levels of expression were noted in the central nucleus of
      raphe; the deep mesencephalic, dorsal raphe, and laterodorsal tegmental nuclei;
      and the ventral periaqueductal gray. In the pons, positive loci included the
      locus coeruleus and the gigantocellular and pontine reticular nuclei. In the
      medulla, high expression was evident in the gigantocellular, intermediate,
      magnocellular, and medullary reticular, spinal trigeminal and cuneate nuclei; and
      the nucleus tractus solitarius. In the spinal cord, moderate to high density of
      staining was found in the ventral, dorsal, and lateral horns, and in the ventral,
      dorsal, and cuneate funiculi. On the other hand, transitory expression was found
      in the diagonal band, bed nucleus of the stria terminalis, amygdala, and the
      lateral mamillary and anterobasal nuclei of the hypothalamus. These studies
      indicate a role for CTR in the activation of some premigratory neuroblasts in the
      CNS as well as a possible role later in an undefined function associated with
      mature neurons of particular nuclei.

PMID- 12508312
TI  - Cellular lining of the sheep pineal recess studied by light-, transmission-, and
      scanning electron microscopy: morphologic indications for a direct secretion of
      melatonin from the pineal gland to the cerebrospinal fluid.
AB  - In the sheep, the pineal hormone melatonin displays nocturnal levels 20 times as
      high in the cerebrospinal fluid of the third ventricle as in the jugular blood.
      Moreover, in the pineal recess, the evagination of the third ventricle into the
      pineal stalk, the levels of melatonin in the cerebrospinal fluid are even higher
      than in the ventral part of the third ventricle. This finding suggests melatonin
      to be secreted directly from the pineal gland to the ventricular lumen of the
      pineal recess of this species. We have, therefore, studied the interface between
      the sheep pineal gland and the cerebrospinal fluid by light-, scanning-, and
      electron microscopy of the pineal recess, as well as the permeability of the
      interface by tracer injections into the third ventricle. First, we show that the
      classic ependymal lining of the third ventricle disappears in the superior part
      of the recess. In this area, bulging pinealocytes, displaying immunoreactivity
      for serotonin, directly appose the cerebrospinal fluid. This pineal-cerebrospinal
      fluid interface of the sheep is large compared with other species, especially
      rodent species. Intraventricular injections of horseradish peroxidase and
      fluorescein isothiocyanate showed that both these tracers could permeate from the
      pineal recess into the sheep pineal parenchyma. This permeation was due to the
      presence of gap and intermediate junctions connecting the pinealocytes apposing
      the ventricular lumen. Thus, our results show that endocrine cells in this
      specialized area of the ventricular system are in direct contact with the
      cerebrospinal fluid. This finding supports the physiological concept of a direct
      secretion of melatonin into the cerebrospinal fluid of the sheep pineal recess.

PMID- 12508313
TI  - Cortical and brainstem neurons containing calcium-binding proteins in a murine
      model of Duchenne's muscular dystrophy: selective changes in the sensorimotor
      cortex.
AB  - In the muscular dystrophic (mdx) mouse, which is characterized by deficient
      dystrophin expression and provides a model of Duchenne's muscular dystrophy, we
      previously demonstrated marked central nervous system alterations and in
      particular a quantitative reduction of corticospinal and rubrospinal neurons and
      pathologic changes of these cells. Prompted by these findings and in view of the
      relations between calcium ions and dystrophin, we analyzed with
      immunohistochemistry the neurons containing the calcium-binding proteins
      parvalbumin, calbindin D28k, and calretinin in cortical areas and brainstem
      nuclei of mdx mice. In the sensorimotor cortex, parvalbumin-positive and
      calbindin-positive neurons, which represent a subset of cortical interneurons,
      were significantly more numerous in mdx mice than in wild-type ones. In addition,
      the laminar distribution of parvalbumin-positive neurons in the motor and
      somatosensory cortical areas of mdx mice was altered with respect to wild-type
      animals. No alterations in the number and distribution were found in the
      parvalbumin- or calbindin-expressing cell populations of the visual and anterior
      cingulate cortices of mdx mice. The pattern of calretinin immunoreactivity was
      normal in all investigated cortical areas. The cell populations containing either
      calcium-binding protein were similar in brainstem nuclei of mdx and wild-type
      mice. The present findings demonstrated selective changes of subsets of
      interneurons in the motor and somatosensory cortical areas of mdx mice.
      Therefore, the data showed that, in the cortices of these mutant animals, the
      previously demonstrated pathologic changes of corticospinal cell populations are
      accompanied by marked alterations in the local circuitry.

PMID- 12508314
TI  - Molecular characterization of the cDNA and localization of the mRNA encoding the
      prohormone convertase PC5-A in the European green frog.
AB  - The structure and distribution of PC5-A, a prohormone convertase that is thought
      to be involved in post-translational processing of peptide hormone and
      neuropeptide precursors, have not been investigated in submammalian vertebrates.
      In the present study, we characterized the cDNA encoding PC5-A in the European
      green frog Rana esculenta. The frog PC5-A cDNA encodes a 913-amino acid protein
      that encompasses a 28-amino acid signal peptide, the Asp/His/Ser catalytic triad
      found in all serine proteinases of the subtilisin family, and two potential N
      linked glycosylation sites located in a C-terminal cysteine-rich domain. Reverse
      transcriptase polymerase chain reaction amplification showed that PC5-A mRNA is
      expressed in various organs including the brain, spinal cord, pituitary, lung,
      liver, intestine, and testis, but not in the stomach and pancreas. The
      distribution of PC5-A mRNA in the frog brain was studied by in situ hybridization
      histochemistry. Intense expression was observed in the mitral cellular layer of
      the olfactory bulb, the nucleus of the diagonal band of Broca, the anterior
      preoptic area, and the suprachiasmatic and ventral hypothalamic nuclei. The
      expression pattern of PC5-A mRNA in the central nervous system of anuran
      amphibians was consistent with the implication of this prohormone convertase in
      the processing of various neuropeptide precursors.

PMID- 12508315
TI  - Alpha-melanophore-stimulating hormone in the brain, cranial placode derivatives,
      and retina of Xenopus laevis during development in relation to background
      adaptation.
AB  - The amphibian Xenopus laevis can adapt the color of its skin to the light
      intensity of the background. A key peptide in this adaptation process is alpha
      melanophore-stimulating hormone (alpha-MSH), which is derived from
      proopiomelanocortin (POMC) and released by the endocrine melanotrope cells in the
      pituitary pars intermedia. In this study, the presence of alpha-MSH in the brain,
      cranial placode derivatives, and retina of developing Xenopus laevis was
      investigated using immunocytochemistry, to test the hypothesis that POMC peptide
      producing neurons and endocrine cells have a common embryonic origin and a common
      function, i.e., controlling each other's activities and/or being involved in the
      process of physiological adaptation. The presence of alpha-MSH-positive cells in
      the suprachiasmatic nucleus, ventral hypothalamic nucleus, epiphysis, and
      endocrine melanotrope and corticotrope cells, which are all involved in
      regulation of adaptation processes, has been detected from stage 37/38 onward.
      This is consistent with the presumed common origin of these cells, the anterior
      neural ridge (ANR) of the neural-plate-stage embryo. The olfactory epithelium and
      the otic and epibranchial ganglia also contain alpha-MSH, indicating that these
      placodal derivatives originate from a common placodal domain continuous with the
      ANR. Furthermore, we demonstrate the presence of alpha-MSH in a subpopulation of
      retinal ganglion cells (RGCs), which is possibly also derived from the ANR.
      Immunoreactivity for alpha-MSH in RGCs that are located in the dorsal part of the
      retina is dependent on the background light intensity, suggesting that these
      cells are involved in the regulation of background adaptation. Taken together,
      the results support the hypothesis that POMC peptide-producing cells have a
      common embryonic origin and are involved in adaptation processes.

PMID- 12508316
TI  - Isolation and characterization of two teleost melanopsin genes and their
      differential expression within the inner retina and brain.
AB  - Melanopsin is a newly discovered photopigment that is believed to be involved in
      the regulation of circadian rhythms in tetrapods. Here we describe the
      characterization of the first two teleost melanopsins (opn4a and opn4b) isolated
      from Atlantic cod (Gadus morhua). These two teleost genes belong to a subgroup of
      melanopsins that also include members from Xenopus, chicken, and Takifugu. In
      situ hybridization revealed that opn4a and opn4b are differentially expressed
      within the retina and brain. In the larval and adult retina, both melanopsins are
      expressed in a subset of cells in the inner retina, resembling amacrine and
      ganglion cells. In addition, opn4a is expressed in the horizontal cells,
      indicating a separate task for this gene. In the brain, the two melanopsins are
      separately expressed in two major retinal and extraretinal photosensitive
      integration centers, namely, the suprachiasmatic nucleus (opn4a) and the habenula
      (opn4b). The expression of opn4a in the suprachiasmatic nucleus in cod is similar
      to the melanopsin expression found in Xenopus. This suggests a conserved role for
      this opsin and an involvement in mediation of nonvisual photoreceptive tasks,
      such as entraining circadian rhythms and/or hypophysiotrophic systems. The
      differential expression of opn4b in the habenula suggests that this gene plays a
      role similar to that of opn4a, in that it is also situated in an area that
      integrates photic inputs from the pineal as well as other brain regions. Thus,
      the habenula may be an additional region that mediates photic cues in teleosts.

PMID- 12508317
TI  - Early development of the Drosophila brain: III. The pattern of neuropile founder
      tracts during the larval period.
AB  - The Drosophila N-CAM homolog Fasciclin II (FasII) is expressed during the
      embryonic period in a subset of central neurons that pioneer the neuropile of the
      larval brain. Toward the end of embryogenesis, FasII expression in axon tracts
      diminishes but resumes from the late first larval instar in an increasingly
      complex pattern of axon tracts that join the tracts laid down in the embryo. We
      present evidence that FasII is expressed in a major fraction of the long axon
      tracts that interconnect different domains of the larval brain. For many tracts,
      FasII expression remains stable throughout larval development and pupal
      development. Therefore, the FasII pattern of axon tracts, along with the mushroom
      body and optic lobe, both of which are also FasII-positive, represents a useful
      set of landmarks that define different regions in the Drosophila brain throughout
      development. In this study, serial confocal brain sections were used to generate
      digital three-dimensional models of larval axon tracts at different stages. These
      models form part of our effort to generate an anatomic framework of Drosophila
      larval brain structure required for accurate localization of gene expression and
      gene function in experimental studies of neural development.

PMID- 12508318
TI  - Early development of the Drosophila brain: IV. Larval neuropile compartments
      defined by glial septa.
AB  - In this study, we have analyzed the architecture of the brain neuropile of the
      Drosophila larva, which is formed by two main structural elements: long axon
      tracts and terminal axonal/dendritic arborizations carrying synapses. By using
      several molecular markers expressed in neurons and glial cells, we show that the
      early larval neuropile is subdivided by glial sheaths into numerous compartments.
      The three-dimensional layout of these compartments and their relationship to the
      pattern of long axon tracts described in the accompanying article (Nassif et al.
      [2003] J. Comp. Neurol 417-434) was modeled by using a three-dimensional
      illustration computer software. On the basis of their location relative to each
      other and to long axon tracts, larval brain compartments can be identified with
      compartments defined by structural and functional criteria for the adult fly
      brain. We find that small precursors of most of the compartments of the adult
      central brain can be identified in the early larva. Changes in brain
      compartmental organization occurring during larval growth are described.
      Neuropile compartments, representing easily identifiable landmark structures,
      will assist in future analyses of Drosophila brain development in which the exact
      location of neurons and their axonal trajectories is of importance.

PMID- 12508319
TI  - Early development of the Drosophila brain: V. Pattern of postembryonic neuronal
      lineages expressing DE-cadherin.
AB  - The Drosophila E-cadherin homolog, DE-cadherin, is expressed postembryonically by
      brain neuroblasts and their lineages of neurons ("secondary lineages"). DE
      cadherin appears in neuroblasts as soon as they can be identified by their
      increase in size and then remains expressed uninterruptedly throughout larval
      life. DE-cadherin remains transiently expressed in the cell bodies and axons of
      neurons produced by neuroblast proliferation. In general, axons of neurons
      belonging to one lineage form tight bundles. The trajectories of these bundles
      are correlated with the location of the neuronal lineages to which they belong.
      Thus, axon bundles of lineages that are neighbors in the cortex travel parallel
      to each other and reach the neuropile at similar positions. It is, therefore,
      possible to assign coherent groups of neuroblasts and their lineages to the
      individual neuropile compartments and long axon tracts introduced in the
      accompanying articles (Nassif et al. [2003] J Comp Neurol 455:417-434; Younossi
      Hartenstein et al. [2003] J Comp Neurol 455:435-450). In this study, we have
      reconstructed the pattern of secondary lineages and their projection in
      relationship to the compartments and Fasciclin II-positive long axon tracts.
      Based on topology and axonal trajectory, the lineages of the central brain can be
      subdivided into 11 groups that can be followed throughout successive larval
      stages. The map of larval lineages and their axonal projection will be important
      for future studies on postembryonic neurogenesis in Drosophila. It also lays a
      groundwork for investigating the role of DE-cadherin in larval brain development.

PMID- 12508321
TI  - Embryological origins and development of the rat diaphragm.
AB  - Textbooks of embryology provide a standard set of drawings and text reflecting
      the traditional interpretation of phrenic nerve and diaphragm development based
      on anatomical dissections of embryonic tissue. Here, we revisit this issue,
      taking advantage of immunohistochemical markers for muscle precursors in
      conjunction with mouse mutants to perform a systematic examination of phrenic
      diaphragm embryogenesis. This includes examining the spatiotemporal relationship
      of phrenic axon outgrowth and muscle precursors during different stages of
      myogenesis. Additionally, mutant mice lacking c-met receptors were used to
      visualize the mesenchymal substratum of the developing diaphragm in the absence
      of myogenic cells. We found no evidence for contributions to the diaphragm
      musculature from the lateral body wall, septum transversum, or esophageal
      mesenchyme, as standard dogma would state. Nor did the data support the
      hypothesis that the crural diaphragm is of distinct embryological origins.
      Rather, we found that myogenic cells and axons destined to form the neuromuscular
      component of the diaphragm coalesce within the pleuroperitoneal fold (PPF). It is
      the expansion of these components of the PPF that leads to the formation of the
      diaphragm. Furthermore, we extended these studies to examine the developing
      diaphragm in an animal model of congenital diaphragmatic hernia (CDH). We find
      that malformation of the PPF mesenchymal substratum leads to the defect
      characteristic of CDH. In summary, the data demonstrates that a significant
      revision of narratives describing normal and pathological development of the
      diaphragm is warranted.

PMID- 12508320
TI  - Immunocytochemical description of five bipolar cell types of the mouse retina.
AB  - With the ever-growing number of transgenic mice being used in vision research, a
      precise knowledge of the cellular organization of the mouse retina is required.
      As with the cat, rabbit, rat, and primate retinae, as many as 10 cone bipolar
      types and one rod bipolar type can be expected to exist in the mouse retina;
      however, they still have to be defined. In the current study, several
      immunocytochemical markers were applied to sections of mouse retina, and the
      labeling of bipolar cells was studied using confocal microscopy and electron
      microscopy. By using antibodies against the neurokinin-3 receptor NK3R; the
      plasma membrane calcium ATPase1 (PMCA1); and the calcium (Ca)-binding proteins
      CaB1, CaB5, caldendrin, and recoverin, three different OFF-cone bipolar cells
      could be identified. One type of ON-cone bipolar cell was identified through its
      immunoreactivity for CaB5 and PMCA1. Rod bipolar cells, comparable in morphology
      to those of other mammalian retinae, expressed protein kinase Calpha and CaB5. It
      was also shown that putative OFF-cone bipolar cells receive light signals through
      flat contacts at the cone pedicle base, whereas ON-cone bipolar signaling
      involves invaginating contacts. The distribution of the kainate receptor subunit
      GluR5 was studied by confocal and electron microscopy. GluR5 was expressed at
      flat bipolar cell contacts; however, it appears to be involved with only certain
      types of OFF-cone bipolar cells. This suggests that different bipolar cell types
      receive their light signals through different sets of glutamate receptors.

PMID- 12508322
TI  - Apoptosis following peripheral sensory deafferentation in the olfactory bulb of
      adult zebrafish.
AB  - Removal of the olfactory organ in adult zebrafish results in a significant
      decrease in volume of the ipsilateral olfactory bulb. The current study
      investigated the potential role of apoptosis in this phenomenon. It was
      hypothesized that cells in the adult olfactory bulb normally undergo minimal
      apoptosis and that apoptosis increases upon removal of sensory stimulation. By
      using both the terminal transferase-mediated deoxyuridine nick-end labeling
      method and bis-benzimide labeling, the current study showed that, in the normal
      adult olfactory bulb, cells exhibiting apoptotic profiles were scarce and were
      localized to the outer layers of the bulb. However, in deafferented animals,
      there was a significant increase in the number of apoptotic cells. The apoptotic
      response occurred in two phases and was confined to the rostral half of the bulb.
      The first phase of cell death peaked at 1 hour postsurgery. These apoptotic
      profiles appeared to be primarily nonneuronal in nature, in that they exhibited
      no immunohistochemical labeling to the neuron-specific protein Hu. The second
      phase of cell death peaked at 24 hours and declined to normal levels by 1 week.
      At the 24 hour time point, only a fraction of the apoptotic cells was neuronal in
      nature. Thus, apoptosis of nonneuronal and neuronal elements accounts for at
      least part of the deafferentation-induced volume decrease in the zebrafish
      olfactory bulb. This model of anterograde transneuronal degeneration will be
      useful in elucidating the afferent signals involved in survival and maintenance
      of mature brain neurons.

PMID- 12508323
TI  - A group of glutamatergic interneurons expressing high levels of both neurokinin-1
      receptors and somatostatin identifies the region of the pre-Botzinger complex.
AB  - The pre-Botzinger complex (pre-BotC) is a physiologically defined group of
      ventrolateral medullary neurons that plays a central role in respiratory rhythm
      generation. These cells are located in a portion of the rostral ventrolateral
      medulla (RVLM) that is difficult to identify precisely for lack of a specific
      marker. We sought to determine whether somatostatin (SST) might be a marker for
      this region. The rat pre-BotC area was defined as a 500-microm-long segment of
      ventrolateral medulla coextensive with the ventral respiratory group. This region
      was identified by juxtacellular labeling of neurons with respiratory-related
      activity and by its location rostral to the phrenic premotor neurons. It
      contained most of the SST-ir neuronal somata of the RVLM. These cells were small
      (107 microm(2)) and expressed high levels of preprosomatostatin mRNA. They were
      strongly neurokinin 1 receptor (NK1R)-ir and were selectively destroyed by
      saporin conjugated with an NK1R agonist (SSP-SAP). Most SST-ir neurons (>90%)
      contained vesicular glutamate transporter 2 (VGLUT2) mRNA, and terminals
      immunoreactive for SST and VGLUT2 protein were found in their midst. Few SST-ir
      neurons contained GAD-67 mRNA (<1%) or preproenkephalin mRNA (6%). Retrograde
      labeling experiments demonstrated that over 75% of the SST-ir neurons project to
      the contralateral pre-BotC area, but none projects to the spinal cord. In
      conclusion, the RVLM contains many neurons that express preprosomatostatin mRNA.
      A subgroup of these cells contains high levels of SST and NK1R immunoreactivity
      in their somata. These glutamatergic interneurons identify a narrow region of the
      RVLM that appears to be coextensive with the pre-BotC of adult rats.

PMID- 12508324
TI  - Expression of androgen receptor mRNA in the late embryonic and early posthatch
      zebra finch brain.
AB  - Zebra finch males sing and females do not, and the underlying neural circuitry in
      males is more developed than that in females. Sex steroid hormones influence the
      development of sex differences in this circuitry, including differences in
      androgen receptor (AR) expression, although the role of androgens has been
      controversial. We isolated a cDNA encoding a portion of the zebra finch AR and
      used in situ hybridization to examine the spatiotemporal pattern of AR mRNA
      expression in the brain during late embryonic development and at hatching. We
      detected AR mRNA in all the major subdivisions of the brain as early as embryonic
      day 10. No qualitative sex differences in AR mRNA expression patterns were
      observed. Cells lining the ventral arm of the lateral telencephalic ventricles
      expressed AR mRNA on embryonic day 11 and posthatching day 1, as did cells lining
      the third ventricle at all three developmental stages examined, suggesting that
      androgens may play a role in early stages of cellular proliferation, migration,
      or differentiation. AR mRNA was also detected in the hippocampus, neostriatum,
      septum, ventromedial archistriatum, hypothalamic regions, dorsal mesencephalon,
      and in and around the brainstem nucleus tracheosyringealis. Our results suggested
      that androgens act early in neural development and therefore may contribute to
      the process of sexual differentiation.

PMID- 12508325
TI  - Connexin immunoreactivity in glial cells of the rat retina.
AB  - The rat retina contains two types of macroglial cells, Muller cells, radial glial
      cells that are the principal macroglial cells of vertebrate retinas, and
      astrocytes associated with the surface vasculature. In addition to the often
      described gap-junctional coupling between astrocytes, coupling also occurs
      between astrocytes and Muller cells. Immunohistochemistry and confocal microscopy
      were used to identify connexins in the retinas of pigmented rats. Several
      antibodies directed against connexin43 stained astrocytes, identified using
      antibodies directed against glial fibrillary acidic protein (GFAP). In addition,
      two connexin43 antibodies stained Muller cells, identified with antibodies
      directed against S100 or glutamine synthetase. Connexin30-immunoreactive puncta
      were confined to the vitreal surface of the retina and colocalized with GFAP
      immunoreactive astrocyte processes. Connexin45 immunoreactivity was associated
      with both astrocytes and Muller cells. We conclude that retinal glial cells
      express multiple connexins, and the patterns of immunostaining that we observe in
      this study are consistent with the expression of connexins30, -43, and possibly 
      45 by astrocytes and the expression of connexins43 and -45 by Muller cells. As
      gap-junction channels may be formed by both homotypic and heterotypic
      hemichannels, and the hemichannels may themselves be homomeric or heteromeric,
      there exists a multitude of possible gap-junction channels that could underlie
      the homotypic coupling between retinal astrocytes and the heterotypic coupling
      between astrocytes and Muller cells.

PMID- 12508326
TI  - Expression and distribution of tuberoinfundibular peptide of 39 residues in the
      rat central nervous system.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) has been recently purified and
      identified as a selective ligand for the parathyroid hormone 2 receptor. As a
      next step toward understanding its functions, we report the expression and
      distribution of TIP39 in the rat central nervous system. In situ hybridization
      histochemistry and immunocytochemistry revealed TIP39-containing cell bodies in
      three distinct areas. The major one comprises the subparafascicular area
      posterior through the intralaminar nucleus of the thalamus; a second is the
      medial paralemniscal nucleus at the pontomesencephalic junction; and a third is
      in the dorsal and dorsolateral hypothalamic areas, which contained a few,
      scattered cell bodies. We found, in contrast to the highly restricted
      localization of TIP39-containing cell bodies, a much more widespread localization
      of TIP39-containing fibers. The highest density of fibers was observed in limbic
      areas such as the septum, the amygdala, and the bed nucleus of the stria
      terminalis; in areas involved in endocrine regulation, such as the hypothalamic
      dorsomedial, paraventricular, periventricular, and arcuate nuclei; in auditory
      areas, such as the ectorhinal and temporal cortices, inferior colliculus, medial
      geniculate body, and some of the nuclei of the superior olivary complex; and in
      the dorsolateral funiculus of the spinal cord. The localization of TIP39
      containing nuclei and fibers provides an anatomical basis for previously
      demonstrated endocrine and nociceptive effects of TIP39 and suggests additional
      functions for TIP39, one apparent candidate being the regulation of auditory
      information processing.

PMID- 12508327
TI  - Introduction: psychosocial consequences of the war in the region of former
      Yugoslavia.
AB  - Editorials usually reflect research topics addressed in the articles which follow
      them as well as highlight central issues, providing an overview of the topic and
      sometimes outlining its historical development. Most of this is true for this
      editorial, but there is--unfortunately--an immediate connection to the current
      political situation as well: I am writing this two weeks after the attacks on the
      World Trade Center, and many people all over the world are afraid that war may
      now threaten countries not affected by war for many years. The threat of war
      makes us think more about the multiple medical and psychosocial consequences
      which follow it. Yet, there is no such thing as "war." Each war has its own
      profile of events which interact with the particular societies involved and with
      the people in the war region.

PMID- 12508328
TI  - Posttraumatic stress symptoms in Croatian children exposed to war: a prospective
      study.
AB  - This study examined symptoms of posttraumatic stress in 252 school-aged children
      from Osijek, Croatia, which was subjected to massive military attacks from
      Yugoslavian forces. The children's symptoms were assessed in 1994 while the war
      was still going on and 30 months later when the war was over. In addition to
      changes in posttraumatic stress disorder symptoms over time, the study examined
      the predictive power of (a) different types and number of war traumata, (b) loss
      of social community, (c) the children's demographic characteristics (age and
      gender), (d) types of coping strategies and locus of control, and (e) the
      perceived availability of different kinds of social support. Although symptoms of
      posttraumatic stress declined over time, 10% of the children reported a severe
      level of symptomatology 30 months after the war. The results supported the
      hypothesized predictive power of all investigated factors for predicting short-
      and long-term posttraumatic stress reactions.

PMID- 12508329
TI  - Determinants of posttraumatic adjustment in adolescents from Sarajevo who
      experienced war.
AB  - The purpose of this study was to examine risk and protective factors of postwar
      adjustment among adolescents from Sarajevo who have been exposed to war traumas
      during the war in Bosnia and Herzegovina. More specifically, we wanted to examine
      differential linkages between Posttraumatic Stress Disorder (PTSD) symptoms and
      depression (as outcomes) and (a) war traumas, (b) individual and
      socioenvironmental factors, and (c) cognitive appraisals and coping mechanisms.
      Results of hierarchical multiple regression analyses indicate that dimensions of
      war traumas, individual characteristics, and cognitive appraisals and coping
      mechanisms play a significant role in determining who will have more serious PTSD
      symptoms. Although individual and socioenvironmental factors are the strongest
      predictors of depression, dimensions of war traumas also are significantly
      correlated with depressive symptoms. Common risk factors for more serious
      depression and PTSD symptoms in postwar adjustment were female gender and low
      optimism. While the strongest predictor of posttraumatic stress reactions (PTSR)
      was trauma experience in the category of loss, the strongest predictor of
      depressive symptoms was female gender.

PMID- 12508330
TI  - Posttraumatic Stress Disorder three years after the siege of Sarajevo.
AB  - The goals of this study were to estimate the lifetime prevalence of traumatic
      events, the current prevalence of Posttraumatic Stress Disorder (PTSD), and the
      connection between the kinds of traumatic events experienced and the probability
      of developing PTSD in three study samples in Sarajevo, Bosnia-Herzegovina, three
      years after the end of the war. A total of 311 people surviving the siege of
      Sarajevo were assessed with the Checklist for War Related Experiences (CWE) and
      an adapted version of the Posttraumatic Diagnostic Scale (PDS). The study groups
      consisted of a randomly selected residents sample (n = 98), a group of
      individuals in psychological treatment (n = 114), and a group in medical
      treatment (n = 99). Each individual survived an average of 24 traumatic events.
      According to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.
      (DSM-IV; American Psychiatric Association, 1994) criteria, 18.6% of individuals
      in the residents sample, 32.7% of those in medical treatment, and 38.6% of those
      in psychological treatment developed PTSD.

PMID- 12508331
TI  - The efficacy of a mental health program in Bosnia-Herzegovina: impact on coping
      and general health.
AB  - The efficacy of a community-based psychosocial program in Bosnia-Herzegovina
      during the war and immediate postwar years (1994-1999) was described in this
      article. Ten centers provided various kinds of psychological help in the besieged
      city of Sarajevo and the towns of Zenica, Travnik, and Vitez. Since 1994, an
      intensive monitoring system has documented data on clients, interventions, and
      outcomes. This study focused on the systematic evaluation of counseling
      interventions aimed to alleviate the distress in wartime. The sample consisted of
      3,283 and 1,785 inhabitants of Sarajevo, Zenica, Travnik, and Vitez who filled
      out the GHQ-28 and IES respectively. Pre- and post-assessments were compared
      throughout consecutive years (1994-1999) and across age groups and both sexes.
      Outcomes of these scales reflected very high scores, especially among people
      between 30 and 40 years of age. Furthermore, intake scores increased in time
      rather than decreased. Differences between pre- and postmeasurements are highly
      significant--throughout the years. Analyses revealed substantial proportions of
      clinically recovered or generally improved individual functioning, although some
      clients revealed no improvement.

PMID- 12508332
TI  - Posttraumatic growth after war: a study with former refugees and displaced people
      in Sarajevo.
AB  - Research carried out with survivors of a variety of different traumata indicates
      that a large proportion of them perceive positive changes in themselves after the
      trauma. This study investigated whether posttraumatic growth also could be found
      among people who had been exposed to particularly severe traumata over a period
      of several years (1991 to 1995) during the war in the area of the former
      Yugoslavia. Included in the study were two representative samples of adult former
      refugees and displaced people who lived anywhere in former Yugoslavia before the
      war and were currently living in Sarajevo, Bosnia and Herzegovina, three and a
      half years after the war. The main instrument was a new Bosnian translation of
      the Posttraumatic Growth Inventory. Results indicated some differences in the
      factor structure as compared with the original instrument. The overall means for
      the scale were considerably lower than reported in most studies on other kinds of
      trauma. Younger people reported considerably more growth than older people.

PMID- 12508333
TI  - The effects of dietary fat and caloric content on the body-size estimates of
      Anorexic Profile and normal college students.
AB  - Anorexic-Profile (AP) and Normal-Profile (NP) college-women's body-size estimates
      of a fictitious female student (target) consuming a regular diet of high- vs low
      fat/calorie foods were compared. Participants initially were divided into four
      groups based on scores from the Eating-Disorders Inventory (AP and NP) and Body
      Mass Index Scores (Low and High Body Mass) and then randomly assigned to one of
      four dietary conditions. Participants then rated the estimated body size of the
      target using the Figure-Rating Scale. Significant main effects were found for
      profile status (AP vs NP), caloric content, and fat content. The significant two
      way interaction of profile status and dietary fat revealed a greater increase in
      body-size estimates for AP vs NP participants as the diet of the target changed
      from low to high fat. Results highlight the importance given to dietary fat,
      especially among AP women, when predicting likely effects on body size.

PMID- 12508334
TI  - The Japanese version of the Multiple Affect Adjective Checklist-Revised:
      development and validation.
AB  - In order to develop a Japanese version of the Multiple Affect Adjective Checklist
      Revised (MAACL-R), the 66 scored adjectives were translated into Japanese and
      translated back into English as recommended by Werner and Campbell (1971).
      Confirmatory factor analyses evidenced the existence of five first-order factors
      (i.e., the anxiety, depression, hostility, positive affect, and sensation-seeking
      factors) and the two second-order factors (i.e., the dysphoric and pleasant
      affect factors) underlying the response to the Japanese MAACL-R. Internal
      consistency ranged from .73 to .91, and four-week retest reliability ranged from
      .67 to .74 on the seven scales (Anxiety, Depression, Hostility, Positive Affect,
      Sensation Seeking, Dysphoria, and PASS). Although correlations with the scales of
      the State-Trait Personality Inventory, State-Trait Anxiety Inventory, Center for
      Epidemiologic Studies Depression scale, a sensation-seeking scale, and a
      subjective well-being scale indicated only acceptable discriminant validity,
      adequate convergent validity was evidenced by the examination of these
      correlations. The Japanese version of the MAACL-R seems to be ready for use in
      research.

PMID- 12508335
TI  - Empirical support for interrater reliability of Rorschach Comprehensive System
      coding.
AB  - Although a great deal of data has been published in the past 20 years supporting
      the interrater reliability of the Rorschach, recently commentators have raised
      anew concerns over the interrater reliability of this well-known and frequently
      used measure. An analysis of the literature reveals that these concerns are based
      on a selective review of the literature. The current study reports interrater
      reliability statistics for 70 interpretive Rorschach variables (n = 84), breaking
      down intraclass correlations statistics by base rate. Results confirm the strong
      empirical evidence of the interrater reliability of this measure when scored by a
      well-trained and diverse group of researchers and clinicians. Reliability is
      especially strong and consistent for the high base-rate variables from which
      clinicians often base their interpretations. These data further suggest that
      large samples are needed for stable reliability estimates of low base-rate
      variables and that estimates of the reliability of low base-rate variables are
      subject to error.

PMID- 12508336
TI  - Detection of intentional sub-optimal performance on a computerized finger-tapping
      task.
AB  - Twenty-four undergraduates were assigned to two groups to determine if the T3
      computerized finger-tapping task could discriminate between persons motivated to
      perform optimally and those motivated to perform sub-optimally. Group HI was
      instructed to simulate a head-injured person undergoing an insurance evaluation,
      whereas group J was instructed to simulate an applicant undergoing a job
      interview. Group HI tapped slower, demonstrated less fatigue, less similarity
      between their right- and left-hand performance, and showed less of a speed
      advantage for the preferred hand. While group HI displayed less variability for
      the non-preferred hand, the groups did not differ on variability for the
      preferred hand. Therefore, the T3 successfully discriminates on multiple measures
      between persons simulating optimal and sub-optimal performance.

PMID- 12508337
TI  - Client and therapist reasons for termination: a conceptualization and preliminary
      validation.
AB  - While the comparison of client and therapist reasons for termination might shed
      light on their respective views of outcome and process, only one published study
      has examined directly the reasons given by therapist-client pairs. One barrier to
      such research is the absence of a systematic conceptualization of reasons for
      termination that incorporates both therapist and client perspectives. This
      article describes a comprehensive conceptualization, drawn from the existing
      literature, and applies a coding system based on that conceptualization to
      naturalistic clinical data from 123 therapist-client pairs in a psychology
      training clinic. Coders were able to categorize reliably open-ended client data
      into reasons for termination. For therapist and client data, the relationships
      between coding categories and participants' outcome ratings, generally were
      consistent with expectations, providing limited validation. Some support was
      found for concordance between therapist and client reasons, especially for those
      related to therapist or client departures, which were prominent in this setting.
      As expected, however, therapists were more likely than clients to endorse success
      as a reason for termination. Negative client feelings about therapy, including
      dissatisfaction, were reported infrequently as reasons for termination, and with
      little agreement between clients and therapists, but this may be due to
      methodological limitations.

PMID- 12508338
TI  - A confirmatory factor analysis of a self-report version of the Liebowitz Social
      Anxiety Scale.
AB  - One of the most popular measures of social phobia is the Liebowitz Social Anxiety
      Scale (LSAS; Liebowitz, 1987). The LSAS is a 24-item semi-structured interview
      measure of fear and avoidance experienced in a range of social and performance
      situations. Recently, the LSAS has been modified to a self-report version (LSAS
      SR) by several independent groups (Cox, Ross, Swinson, & Direnfeld, 1998; Fresco
      et al., 2001; Mancini, Van Ameringen, & Oakman, 1999). A self-report version
      offers ease of administration, but it may differ from the structured interview
      version in its psychometric properties. We conducted confirmatory factor analyses
      of the self-report version of the LSAS using data from a sample of 188
      outpatients with anxiety disorders. The structure and psychometric properties of
      the LSAS-SR are highly similar to that of the LSAS and robust across groups of
      patients with a variety of primary anxiety disorders. We argue in favor of
      adopting the 4-factor model for the LSAS proposed by Safren et al. (1999) instead
      of the models implied by the scoring instructions for the LSAS.

PMID- 12508339
TI  - Predicting psychological mindedness from personality style and attachment
      security.
AB  - The aim of this study was to increase the construct validity of the Psychological
      Mindedness Scale (PM Scale) by investigating its relationship to well-established
      measures of personality style (NEO Five-Factor Inventory) and attachment security
      (Inventory of Parent and Peer Attachment). Personality and attachment variables
      functioned as differential predictors of psychological mindedness (PM). Openness
      to Experience emerged as the best predictor of PM, followed by Extraversion,
      Neuroticism (inversely related to PM), and Attachment to Peers. Neither
      Attachment to Mother nor Attachment to Father predicted PM. The results of this
      study indicate that PM is related positively to healthy, rather than
      pathological, personal and interpersonal constructs.

PMID- 12508340
TI  - Hereditary pancreatitis.
AB  - Hereditary pancreatitis is an autosomal dominant condition, which results in
      recurrent attacks of acute pancreatitis, progressing to chronic pancreatitis
      often at a young age. The majority of patients with hereditary pancreatitis
      express one of two mutations (R122H or N29I) in the cationic trypsinogen gene
      (PRSS1 gene). It has been hypothesised that one of these mutations, the R122H
      mutation causes pancreatitis by altering a trypsin recognition site so preventing
      deactivation of trypsin within the pancreas and prolonging its action, resulting
      in autodigestion. Families with these two mutations have been identified in many
      countries and there are also other rarer mutations, which have also been linked
      to hereditary pancreatitis. Patients with hereditary pancreatitis present in the
      same way as those with sporadic pancreatitis but at an earlier age. It is common
      for patients to remain undiagnosed for many years, particularly if they present
      with non-specific symptoms. Hereditary pancreatitis should always be considered
      in patients who present with recurrent pancreatitis with a family history of
      pancreatic disease. If patients with the 2 common mutations are compared, those
      with the R122H mutation are more likely to present at a younger age and are more
      likely to require surgical intervention than those with N29I. Hereditary
      pancreatitis carries a 40 % lifetime risk of pancreatic cancer with those
      patients aged between 50 to 70 being most at risk in whom screening tests may
      become important.

PMID- 12508341
TI  - Helicobacter pylori infection and respiratory diseases: a review.
AB  - In the past few years, a variety of extradigestive disorders, including
      cardiovascular, skin, rheumatic and liver diseases, have been associated with
      Helicobacter pylori (H. pylori) infection. The activation of inflammatory
      mediators by H. pylori seems to be the pathogenetic mechanism underlying the
      observed associations. The present review summarizes the current literature,
      including our own studies, concerning the association between H. pylori infection
      and respiratory diseases. A small number of epidemiological and serologic, case
      control studies suggest that H. pylori infection may be associated with the
      development of chronic bronchitis. A frequent coexistence of pulmonary
      tuberculosis and H. pylori infection has also been found. Moreover, recent
      studies have shown an increased H. pylori seroprevalence in patients with
      bronchiectasis and in those with lung cancer. On the other hand, bronchial asthma
      seems not to be related with H. pylori infection. All associations between H.
      pylori infection and respiratory diseases are primarily based on case-control
      studies, concerning relatively small numbers of patients. Moreover, there is a
      lack of studies focused on the pathogenetic link between respiratory diseases and
      H. pylori infection. Therefore, we believe that larger studies should be
      undertaken to confirm the observed results and to clarify the underlying
      pathogenetic mechanisms.

PMID- 12508342
TI  - Gene expression profiles at different stages of human esophageal squamous cell
      carcinoma.
AB  - AIM: To characterize the gene expression profiles in different stages of
      carcinogenesis of esophageal epithelium. METHODS: A microarray containing 588
      cancer related genes was employed to study the gene expression profile at
      different stages of esophageal squamous cell carcinoma including basal cell
      hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer.
      Principle component analysis was performed to search the genes which were
      important in carcinogenesis. RESULTS: More than 100 genes were up or down
      regulated in esophageal epithelial cells during the stages of basal cell
      hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer.
      Principle component analysis identified a set of genes which may play important
      roles in the tumor development. Comparison of expression profiles between these
      stages showed that some genes, such as P160ROCK, JNK2, were activated and may
      play an important role in early stages of carcinogenesis. CONCLUSION: These
      findings provided an esophageal cancer-specific and stage-specific expression
      profiles, showing that complex alterations of gene expression underlie the
      development of malignant phenotype of esophageal cancer cells.

PMID- 12508343
TI  - Alterations of p53 and PCNA in cancer and adjacent tissues from concurrent
      carcinomas of the esophagus and gastric cardia in the same patient in Linzhou, a
      high incidence area for esophageal cancer in northern China.
AB  - AIM: To characterize the alteration and significance of p53 and PCNA in cancer
      and adjacent tissues of concurrent cancers from the esophagus and gastric cardia
      in the same patient. METHODS: P53 and PCNA protein accumulation in 25 patients
      with concurrent cancers from the esophagus and gastric cardia (CC, concurrent
      carcinomas of esophageal squamous cell carcinoma and gastric cardia
      adenocarcinoma) were detected by immunohistochemical method (ABC). RESULTS: In CC
      patients, both esophageal squamous cell carcinoma (SCC) and gastric cardia
      adenocarcinoma (GCA) tissues showed different positive immunostaining extent of
      p53 and PCNA protein (P>0.05). The positive immunostaining rates for p53 and PCNA
      were 60 % (15/25) and 92 % (23/25), respectively in SCC; and 40 % (10/25) and 88
      % (22/25), respectively in GCA. "Diffuse" immunostaining pattern was frequently
      observed in both p53 and PCNA. High coincidence rates for p53 and PCNA positive
      staining were observed in SCC and GCA from the same patients, and accounted for
      56 % and 96 %. In SCC patients, with the lesions progressed from normal
      esophageal epithelium (NOR) to basal cell hyperplasia (BCH) to dysplasia (DYS) to
      carcinoma in situ (CIS) to SCC, the positive rates for p53 were 27 %, 50 %, 50 %,
      29 % and 72 %, and 55 %, 70 %,75 %, 71 % and 93 % for PCNA, respectively. In GCA,
      with the lesions progressed from normal gastric cardia epithelium to DYS to CIS
      to GCA, the positive rates of p53 expression were 44 %, 27 %, 22 % and 36 %
      respectively, the difference was not significant; the positive rates of PCNA
      protein expression were 67 %, 64 %, 67 % and 86 %, respectively. The chi(2) test,
      Fisher's Exact Test, Mantel-Haenszel chi(2) Test and Kappa Test were used for the
      statistics. CONCLUSION: The high coincident alterations for P53 and PCNA in SCC
      and GCA from the same patient indicate the possibility of similar molecular
      basis, which provides important molecular basis and etiological clue for similar
      geographic distribution and risk factors in SCC and GCA.

PMID- 12508344
TI  - A new three-layer-funnel-shaped esophagogastric anastomosis for surgical
      treatment of esophageal carcinoma.
AB  - AIM: To reduce the incidence of postoperative anastomotic leak, stenosis,
      gastroesophageal reflux (GER) for patients with esophageal carcinoma, and to
      evaluate the conventional method of esophagectomy and esophagogastroplasty
      modified by a new three-layer-funnel-shaped (TLF) esophagogastric anastomotic
      suturing technique. METHODS: From January 1997 to October 1999, patients with
      clinical stage I and II (IIa and IIb) esophageal carcinoma, which met the
      enrollment criteria, were surgically treated by the new method (Group A) and by
      conventional operation (Group B). All the patients were followed at least for 6
      months. Postoperative outcomes and complications were recorded and compared with
      the conventional method in the same hospitals and with that reported previously
      by McLarty et al in 1997 (Group C). RESULTS: 58 cases with stage I and II (IIa
      and IIb) esophageal carcinoma, including 38 males and 20 females aged from 34 to
      78 (mean age: 57), were surgically treated by the TLF anastomosis and 64 by
      conventional method in our hospitals from January 1997 to October 1999. The
      quality of swallowing was improved significantly (Wilcoxon W=2 142, P=0.0 001) 2
      to 3 months after the new operation in Group A. Only one patient had a blind
      anastomatic fistula diagnosed by barium swallow test 2 months but healed up 3
      weeks later. Postoperative complications occurred in 25 (43 %) patients,
      anastomotic stenosis in 8 (14 %), and GER in 13 (22 %). The incidences of
      postoperative anastomotic leak, stenosis and GER were significantly decreased by
      the TLF anastomosis method compared with that of conventional methods
      (chi(2)=6.566, P=0.038; chi(2)=10.214, P=0.006; chi(2)=21.265, P=0.000).
      CONCLUSION: The new three-layer-funnel-shaped esophagogastric anastomosis
      (TLFEGA) has more advantages to reduce postoperative complications of anastomotic
      leak, stricture and GER.

PMID- 12508345
TI  - Silencing-specific methylation and single nucleotide polymorphism of hMLH1
      promoter in gastric carcinomas.
AB  - AIM: To investigate CpG methylation and single nucleotide polymorphism (SNP) of a
      specific promoter region of hMLH1 in primary gastric carcinoma. METHODS: Primary
      gastric carcinomas (n=80), their corresponding normal mucosal samples, and
      gastric mucosal biopsies from normal/gastritis control patients (n=54) were used.
      Hypermethylation at -253 nt and -251 nt in relation with the translational start
      site and SNP of a silencing specific region (-339 nt-46 nt) in the hMLH1 promoter
      were analyzed by Bst UI-combined bisulfite assay (COBRA), denaturing high
      performance liquid chromatogram (DHPLC), and sequencing. RESULTS: (A) The
      specific methylation at -253 nt and -251 nt was observed in 2 of 60 primary
      gastric carcinomas, but neither in all of the corresponding mucosa nor in
      normal/gastritis samples, by Bst UI-COBRA and DHPLC. (B) The hMLH1 promoter was
      methylated homogeneously in the xenograft of the primary gastric carcinoma with
      the methylated and unmethylated hMLH1. (C) The pattern of SNP at -93 nt of the
      hMLH1 promoter in 54 Chinese patients with gastric carcinoma was the same as that
      in the control patients: 51 % was A/G heteroalleles, 34 % and 15 % were A/A and
      G/G homoalleles, respectively. CONCLUSION: Biallelic inactivation of hMLH1 by
      epigenetic silencing existed in human primary gastric carcinoma homogeneously.
      Hypermethylation of hMLH1 may play a role in the early stage of development of a
      few gastric carcinomas. The SNP at -93 nt is not related to the susceptibility of
      gastric carcinomas.

PMID- 12508346
TI  - A novel gene, GCRG224, is differentially expressed in human gastric mucosa.
AB  - AIM: To clone genes that may predispose us to human gastric cancer and to analyze
      it's expression in gastric tissues. METHODS: Specimens of paired tumor, paratumor
      and normal gastric mucosa tissues collected from fifteen patients who suffered
      from stomach antrum adenocarcinoma were used for analysis. Seven out of the
      fifteen cases were first studied by fluorescent differential display reverse
      transcription polymerase chain reaction (DDTR-PCR) analysis. The differentially
      expressed bands of interest were cloned, analyzed by Northern blot, sequencing
      and RT-PCR. Through BLAST, the sequencing results were compared with GenBank
      database for homology analysis. In situ hybridization with DIG-labeled cRNA
      probes was used to analyze the expression of interesting cDNA bands in paraffin
      embedded paired normal gastric mucosa and cancer tissues isolated from 30 gastric
      adenocarcinoma patients. RESULTS: DDRT-PCR showed that one of the interesting
      cDNA bands, which was named W2, expressed much higher in all seven tested tumor
      and paratumor samples than in their normal counterparts, it was sub-cloned into a
      pGEM-T Easy vector. Two subclones were subsequently obtained. One of the
      subclone, GCRG224, was studied further. The sequencing result showed that GCRG224
      consisted of 1 159 base pairs and had one open reading frame (ORF). It located at
      human chromosome 11q14. No homologue was found in GenBank database with GCRG224
      ORF. This nucleotide sequence data were submitted to GenBank with accession No.
      AF438406. RT-PCR showed that GCRG224 expressed higher in 11/15 gastric cancer
      tissues than in non-tumor tissues. However, the result of Northern blot analysis
      showed a higher GCRG224 expression in the non-tumor tissue than in the tumor one.
      Human multiple tissue Northern blot analysis revealed that GCRG224 also expressed
      in human normal colon tissue, and peripheral blood leukocyte. In situ
      hybridization analysis showed that only 5/30 adenocarcinoma, 3/18 dysplasia and
      6/18 intestinal metaplasia showed higher GCRG224 expression level than the normal
      gastric glands. However, GCRG224 was over-expressed predominantly in 26/30 cases
      of normal mucosal epithelium. CONCLUSION: A novel gene named GCRG224 was
      identified from human gastric mucosal tissue. It overexpressed in almost all
      gastric mucosal epithelium but only a small portion of cancer and precancerous
      leisions. The role of GCRG224 expression in gastric epithelium needs further
      study.

PMID- 12508347
TI  - PTEN encoding product: a marker for tumorigenesis and progression of gastric
      carcinoma.
AB  - AIM: To detect the expression of PTEN encoding product in normal mucosa,
      intestinal metaplasia (IM), dysplasia and carcinoma of the stomach, and to
      investigate its clinical implication in tumorigenesis and progression of gastric
      carcinoma. METHODS: Formalin-fixed paraffin embedded specimens from 184 cases of
      gastric carcinoma, their adjacent normal mucosa, IM and dysplasia were evaluated
      for PTEN protein expression by SABC immunohistochemistry. PTEN expression was
      compared with tumor stage, lymph node metastasis, Lauren's and WHO's histological
      classification of gastric carcinoma. Expression of VEGF was also detected in 60
      cases of gastric carcinoma and its correlation with PTEN was concerned. RESULTS:
      The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 %
      (4/6) and 47.8 %(88/184) in normal mucosa, IM, dysplasia and carcinoma of the
      stomach, respectively. The positive rates in dysplasia and carcinoma were lower
      than in normal mucosa and IM (P<0.01). Advanced gastric cancers expressed less
      frequent PTEN than early gastric cancer (42.9 % vs 67.6 %, P<0.01). The positive
      rate of PTEN protein was lower in gastric cancer with than without lymph node
      metastasis (40.3 % vs 63.3 %, P<0.01). PTEN was less expressed in diffuse-type
      than in intestinal-type gastric cancer (41.5 % vs 57.8 %, P<0.05). Signet ring
      cell carcinoma showed the expression of PTEN at the lowest level (25.0 %, 7/28);
      less than well and moderately differentiated ones (P<0.01). Expression of PTEN
      was not correlated with expression of VEGF (P>0.05). CONCLUSION: Loss or reduced
      expression of PTEN protein occures commonly in tumorigenesis and progression of
      gastric carcinoma. It is suggested that PTEN can be an objective marker for
      pathologically biological behaviors of gastric carcinoma.

PMID- 12508348
TI  - Relationship between lymph node sinuses with blood and lymphatic metastasis of
      gastric cancer.
AB  - AIM: To elucidate the relationship between lymph node sinuses with blood and
      lymphatic metastasis of gastric cancer. METHODS: Routine autopsy was carried out
      in the randomly selected 102 patients (among them 100 patients died of various
      diseases, and 2 patients died of non-diseased reasons), their superficial lymph
      nodes locating in bilateral necks (include supraclavicle), axilla, inguina,
      thorax, and abdomen were sampled. Haematoxylin-Eosin staining was performed on 10
      % formalin-fixed and paraffin-embedded lymph node tissue sections (5 um). The
      histological patterns of the lymph sinuses containing blood were observed under
      light microscope. The expression of CD31, a marker for endothelial cell, was
      detected both in blood and non-blood containing lymph node sinuses with the
      method of immunohistochemistry. RESULTS: Among the 1 322 lymph nodes sampled from
      the autopsies of 100 diseased cases, lymph node sinuses containing blood were
      found in 809 lymph nodes sampled from 91 cases, but couldn't be seen in the lymph
      nodes sampled from the non-diseased cases. According to histology, we divided the
      blood containing lymph node sinuses into five categories: vascular-opening sinus,
      blood-deficient sinus, erythrophago-sinus, blood-abundant sinus, vascular
      formative sinus. Immunohistochemical findings showed that the expression of CD31
      was strongly positive in vascular-formative sinuses and some vascular-opening
      sinuses while it was faint in blood-deficient sinuses, erythrophago-sinuses and
      some vascular-opening sinuses. It was almost negative in blood-abundant sinus and
      non-blood containing sinus. CONCLUSION: In the state of disease, the phenomenon
      of blood present in the lymph sinus is not uncommon. Blood could possibly enter
      into the lymph sinuses through the lymphaticovenous communications between the
      veins and the sinuses in the node. Lymph circulation and the blood circulation
      could communicate with each other in the lymph node sinuses. The skipping and
      distal lymphatic metastasis of gastric cancer may have some connection with the
      blood containing lymph node sinuses.

PMID- 12508349
TI  - Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by
      benzo (a) pyrene and chemopreventive mechanisms.
AB  - AIM: To explore the inhibition of conjugated linoleic acid isomers in different
      purity (75 % purity c9,t11-, 98 % purity c9,t11- and 98 % purity t10,c12-CLA) on
      the formation of forestomach neoplasm and chemopreventive mechanisms. METHODS:
      Forestomach neoplasm model induced by B(a)P in KunMing mice was established. The
      numbers of tumor and diameter of each tumor in forestomach were counted; the mice
      plasma malondialdehyde (MDA) were measured by TBARS assay; TUNEL assay was used
      to analyze the apoptosis in forestomach neoplasia and the expression of MEK-1,
      ERK-1, MKP-1 protein in forestomach neoplasm were studied by Western Blotting
      assay. RESULTS: The incidence of neoplasm in B(a)P group, 75 % purity c9, t11-CLA
      group, 98 % purity c9,t11-CLA group and 98 % purity t10, c12-CLA group was 100 %,
      75.0 %(P>0.05), 69.2 % (P<0.05) and 53.8 % (P<0.05) respectively and the effect
      of two CLA isomers in 98 % purity on forestomach neoplasia was significant; CLA
      showed no influence on the average tumor numbers in tumor-bearing mouse, but
      significantly decreased the tumor size, the tumor average diameter of mice in 75
      % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10, c12
      CLA group was 0.157+/-0.047 cm, 0.127+/-0.038 cm and 0.128+/-0.077 cm (P<0.05)
      and 0.216+/-0.088 cm in B(a)P group; CLA could also significantly increase the
      apoptosis cell numbers by 144.00+/-20.31, 153.75+/-23.25, 157.25+/-15.95(P<0.05)
      in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity
      t10,c12-CLA group (30.88+/-3.72 in BP group); but there were no significant
      differences between the effects of 75 % purity c9,t11-CLA and two isomers in 98 %
      purity on tumor size and apoptotic cell numbers; the plasma levels of MDA in were
      increased by 75 % purity c9,t11-CLA, 98 % purity c9,t11-CLA and 98 % purity
      t10,c12-CLA. The 75 % purity c9,t11-CLA showed stronger inhibition; CLA could
      also inhibit the expression of ERK-1 protein and promote the expression of MKP-1
      protein, however no influence of CLA on MEK-1 protein was observed. CONCLUSION:
      Two isomers in 98 % purity show stronger inhibition on carcinogenesis. However,
      the inhibitory mechanisms of CLA on carcinogenesis is complicated, which may be
      due to the increased mice plasma MDA, the inducing apoptosis in tumor tissues.
      And the effect of CLA on the expression of ERK-1 and MKP-1 may be one of the
      mechanisms of the inhibition of CLA on the tumor.

PMID- 12508350
TI  - Association between pepsinogen C gene polymorphism and genetic predisposition to
      gastric cancer.
AB  - AIM: To identify a molecular marker for gastric cancer, and to investigate the
      relationship between the polymorphism of pepsinogen C (PGC) gene and the genetic
      predisposition to gastric cancer. METHODS: A total of 289 cases were involved in
      this study. 115 cases came from Shenyang area, a low risk area of gastric cancer,
      including 42 unrelated controls and 73 patients with gastric cancer. 174 cases
      came from Zhuanghe area, a high-risk area of gastric cancer, including 113
      unrelated controls, and 61 cases from gastric cancer kindred families. The
      polymorphism of PGC gene was detected by polymerase chain reaction (PCR) and the
      relation between the genetic polymorphism of PGC and gastric cancer was examined.
      RESULTS: Four alleles, 31 0bp (allele 1), 400 bp (allele 2), 450 bp (allele 3),
      and 480 bp (allele 4) were detected by PCR. The frequency of allele 1 was higher
      in patients with gastric cancer than that in controls. Genotypes containing
      homogenous allele 1 were significantly more frequent in patients with gastric
      cancer than that in controls (0.33, 0.14, chi(2)=3.86, P<0.05). There was no
      significant difference between the control group of Zhuanghe and the group of
      gastric cancer kindred. But the frequency of allele 1 was higher in control group
      of Zhuanghe area than that in control group of Shenyang area and genotypes
      containing homogenous allele 1 were significantly more frequent in the control
      group of Zhuanghe area than those in control group of Shenyang area (0.33, 0.14,
      chi(2)=4.32, P<0.05). In the group of gastric cancer kindred the frequency of
      allele 1 was significantly higher than that in control group of Shenyang area
      (0.5164, 0.3571, chi(2)=4.47, P<0.05). Genotypes containing homogenous allele 1
      were significantly more frequent in the group of gastric cancer kindred than
      those in control group of Shenyang area (0.36, 0.14, chi(2)=4.91, P<0.05).
      CONCLUSION: These results suggest that there is some relation between pepsinogen
      C gene polymorphism and gastric cancer, and the person with homogenous allele 1
      predisposes to gastric cancer than those with other genotypes. Pepsinogen C gene
      polymorphism may be used as a genetic marker for a genetic predisposition to
      gastric cancer. The distribution of pepsinogen C gene polymorphism in Zhuanghe, a
      high-risk area of gastric cancer, is different from that in Shenyang, a low risk
      area of gastric cancer.

PMID- 12508351
TI  - Helicobacter pylori infection generated gastric cancer through p53-Rb tumor
      suppressor system mutation and telomerase reactivation.
AB  - AIM: To investigate the relationship between Helicobacter pylori (H.pylori)
      infection and the expressions of the p53, Rb, c-myc, bcl-2 and hTERT mRNA in a
      series of diseases from chronic gastritis (CG), intestinal metaplasia type I or
      II(IMI-II), intestinal metaplasia type III (IMIII), mild or modest dysplasia
      (DysI-II), severe dysplasia (DysIII) to gastric cancer(GC) and to elucidate the
      mechanism of gastric carcinogenesis relating to H.pylori infection. METHODS: 272
      cases between 1998 and 2001 were available for the study including 42 cases of
      CG, 46 cases of IMI-II, 25 cases of IMIII, 48 cases of DysI-II, 27 cases of
      DysIII, 84 cases of GC. H.pylori infection and the expressions of p53, Rb, c-myc,
      bcl-2 were detected by means of streptavidin-peroxidase (SP) immunohistochemical
      method. HTERT mRNA was detected by in situ hybridization (ISH). RESULTS: The
      expressions of p53, Rb, c-myc, hTERT mRNA and bcl-2 were higher in the GC than in
      CG, IM, Dys. The expression of c-myc was higher in IMIII with H.pylori infection
      (10/16) than that without infection (1/9) and the positive rate in DysI-II and
      DysIII with H.pylori infection was 18/30 and 13/17, respectively, higher than
      that without infection (4/18 and 3/10, respectively). In our experiment mutated
      p53 had no association with H.pylori infection, the expression of Rb was
      associated with H.pylori infection in GC, but the p53-Rb tumor-suppressor system
      abnormal in DysI-II cases, DysIII and GC cases with H.pylori infection was 21/30,
      15/17 and 48/48 respectively, higher than non-infection groups (4/18, 3/10,
      28/36). Furthermore the level of hTERT mRNA in GC with H.pylori infection (47/48)
      was higher than that without infection (30/36), however the relationship between
      bcl-2 and H.pylori was only in IMIII. C-myc had a close association with hTERT
      mRNA in DysIII and GC (P=0.0 253,0.0 305 respectively). CONCLUSION: In the
      gastric carcinogenesis, H.pylori might cause the severe imbalance of
      proliferation and apoptosis in the precancerous lesions (IMIII and GysIII) first,
      leading to p53-Rb tumor-suppressor system mutation and telomerase reactivation,
      and finally causes gastric cancer.

PMID- 12508352
TI  - Angiostatin up-regulation in gastric cancer cell SGC7901 inhibits tumorigenesis
      in nude mice.
AB  - AIM: To explore the influence of angiostatin up-regulation on the biologic
      behavior of gastric cancer cells in vitro and in vivo, and the potential of
      angiostatin gene therapy in the treatment of human gastric cancer. METHODS: Mouse
      angiostatin cDNA was subcloned into the eukaryotic expression vector pcDNA3.1(+)
      and identified by restriction endonucleases digestion and sequencing. The
      recombinant vector pcDNA3.1(+)-angio was transfected into human gastric cancer
      cells SGC7901 with liposome and paralleled with the vector control and the mock
      control. Angiostatin transcription and protein expression were examined by RT-PCR
      and Western blot in the stable cell lines selected by G418. Cell proliferation
      and growth in vitro of the three groups were observed respectively under
      microscope, cell number counting and FACS. The cells overexpressing angiostatin,
      vector transfected and untreated were respectively implanted subcutaneously into
      nude mice. After 30 days the size of tumors formed was measured, and microvessel
      density count (MVD) in the tumor tissues was assessed by immunohistochemistry
      with the primary anti-vWF antibody. RESULTS: The recombinant vector pcDNA3.1(+)
      angio was confirmed with the correct sequence of mouse angiostatin under the
      promoter CMV. After 30 d of transfection and selection with G418, macroscopic
      resistant cell clones were formed in the experimental group transfected with
      pcDNA 3.1(+)-angio and the vector control. But no untreated cells survived in the
      mock control. Angiostatin mRNA transcription and protein expression were detected
      in the experimental group. No significant differences were observed among the
      three groups in cell morphology, cell growth curves and cell cycle phase
      distributions in vitro. However, in nude mice model, markedly inhibited
      tumorigenesis and slowed tumor expansion were observed in the experimental group
      as compared with the controls, which was paralleled with decreased microvessel
      density in and around tumor tissues (P<0.05). CONCLUSION: Angiostatin does not
      directly inhibit human gastric cancer cell proliferation and growth in vitro, but
      exerts its anti-tumor functions through antiangiogenesis in a paracrine way in
      vivo.

PMID- 12508353
TI  - Synergistic effect of cell differential agent-II and arsenic trioxide on
      induction of cell cycle arrest and apoptosis in hepatoma cells.
AB  - AIM: To illustrate the possible role of cell differential agent-II (CDA-II) in
      the apoptosis of hepatoma cells induced by arsenic trioxide (As(2)O(3)). METHODS:
      Hepatoma cell lines BEL-7402 and HepG2 were treated with As(2)O(3) together with
      CDA-II. Cell surviving fraction was determined by MTT assay; morphological
      changes were observed by immunofluorescence staining of Hoechst 33,258; and cell
      cycle and the apoptosis index were determined by flow cytometry (FCM). RESULTS:
      Cytotoxicity of CDA-II was low. Nevertheless, CDA-II could strongly potentiate
      arsenic trioxide-induced apoptosis. At 1.0 g/L CDA-II, IC(50) of As(2)O(3) in
      hepatoma cell lines was reduced from 5.0 micromol/L to 1.0 micromol/L (P<0.01).
      The potentiation of apoptosis was dependent on the dosage of CDA-II. FCM
      indicated that in hepatoma, cell growth was inhibited by CDA-II at lower
      concentrations (<2.0 g/L) primarily by arresting at S and G(2) phase, and at
      higher concentrations (>2.0 g/L) apoptotic cell and cell cycle arresting at G(1)
      phase increased proportionally. The combination of two drugs led to much higher
      apoptotic rates, as compared with the either drug used alone. CONCLUSION: CDA-II
      can strongly potentiate As(2)O(3)-induced apoptosis in hepatoma cells, and two
      drugs can produce a significant synergic effect.

PMID- 12508354
TI  - Relationship between the imaging features and pathologic alteration in hepatoma
      of rats.
AB  - AIM: The imaging features of MRI and DSA, using the models of implanted and
      induced hepatoma, were investigated in rats. METHODS: CBRH3 cancer cells were
      implanted for different liver site of rat liver and the diethylnitrosoamine was
      given orally to rats in order to induce liver cancer. Both experimental groups
      were detected by magnetic resonance imaging (MRI), digital subtraction
      angiography (DSA) and morphologic assay. RESULTS: Hypointensity on T1WI and
      homogenous high signal intensity on T2WI in MRI, and ring-like abnormal stain on
      DSA were found in implanted cancer. Induced cancers appeared as homogeneous or
      heterogeneous hypointensity on T1WI (10 cases), and equal or slight high
      intensity on T2WI (8 cases), but some as hypointensity on T2WI (2 cases).
      CONCLUSION: The imaging features of implanted cancers were similar to that of
      human liver metastases. Therefore, it could serve as an experimental model of
      human liver metastatic tumor. The imaging feature of induced cancers, whereas,
      were similar to that of human primary liver cancer. It could be use as an
      experimental model of human primary liver cancer.

PMID- 12508355
TI  - Synergetic anticancer effect of combined quercetin and recombinant adenoviral
      vector expressing human wild-type p53, GM-CSF and B7-1 genes on hepatocellular
      carcinoma cells in vitro.
AB  - AIM: This study investigated the anti-cancer effect of combined quercetin and a
      recombinant adenovirus vector expressing the human p53, GM-CSF and B7-1 genes
      (designated BB-102) on human hepatocellular carcinoma (HCC) cell lines in vitro.
      METHODS: The sensitivity of HCC cells to anticancer agents was evaluated by 3
      (4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The
      viability of cells infected with BB-102 was determined by trypan blue exclusion.
      The expression levels of human wild-type p53, GM-CSF and B7-1 genes were
      determined by Western blot, enzyme-linked immunosorbent assay (ELISA) and flow
      cytometric analysis, respectively. The apoptosis of BB-102-infected or quercetin
      treated HCC cells was detected by terminal deoxynucleotidyl transferase (TdT)
      assay or DNA ladder electrophoresis. RESULTS: Quercetin was found to suppress
      proliferation of human HCC cell lines BEL-7402, HuH-7 and HLE, with peak
      suppression at 50 micromol/L quercetin. BB-102 infection was also found to
      significantly suppress proliferation of HCC cell lines. The apoptosis of BB-102
      infected HCC cells was greater in HLE and HuH-7 cells than in BEL-7402 cells.
      Quercetin did not affect the expression of the three exogenous genes in BB-102
      infected HCC cells (P>0.05), but it was found to further decrease proliferation
      and promote apoptosis of BB-102-infected HCC cells. CONCLUSION: BB-102 and
      quercetin synergetically suppress HCC cell proliferation and induce HCC cell
      apoptosis, suggesting a possible use as a combined anti-cancer agent.

PMID- 12508356
TI  - Construction of IL-2 gene-modified human hepatocyte and its cultivation with
      microcarrier.
AB  - AIM: To construct interleukin-2 gene-modified human hepatocyte line (L-02/IL-2)
      and investigate the changes of the function of liver cells and IL-2 secretion in
      culture with microcarrier,laying the foundation for further experimentation on
      hepatocyte transplantation. METHODS: hIL-2 gene was transduced into L-02
      hepatocytes by recombinant retroviral vector pLNCIL-2, and the changes of
      morphology and clonogenicity rate of the transduced cells were observed, the
      secretion levels of hIL-2 in cultural supernatant were detected by ELISA and NeoR
      gene was amplified by PCR. The growth of L-02/IL-2, the special biochemistry
      items and the levels of IL-2 were detected after cultivation with microcarrier.
      RESULTS: The clonogenicity rate of the L-02/IL-2 cells was lower than that of L
      02/Neo cells and L-02 cells. The levels of hIL-2 could reach 32,000 pg/10(6)
      cells per day and kept secreting for more than ten weeks. NeoR gene segment was
      respectively obtained by PCR from both L-02/IL-2 and L-02/Neo cell's genomic DNA.
      At the 6(th) day in culture with microcarrier, the matrix-induced liver cell
      aggregates were formed, the number of alive L-02/IL-2 cell were 16.8+/-0.53 x
      10(6)/flask and the levels of ALB and UREA were 52.54+/-1.28 mg/L and 5.29+/-0.17
      mmol/L, respectively. These data had not significantly changed as compared with
      those of L-02 cells (P>0.05); However, the levels of IL-2 in IL-2/L-02 cells
      remarkably exceeded that in L-02 cells in the whole culture process (P<0.001).
      CONCLUSION: The IL-2 gene-modified hepatocyte line has been successfully
      constructed. The L-02/IL-2 cellular aggregates cultured with microcarrier have a
      high capacity of IL-2 production as well as protein synthesis and amino acid
      metabolism.

PMID- 12508357
TI  - Effects of p16 gene on biological behaviours in hepatocellular carcinoma cells.
AB  - AIM: To investigate the effects of p16 gene on biological behaviours in
      hepatocellular carcinoma cells. METHODS: HCC cell lines SNU-449 and HepG2.2.15
      were infected respectively by a replication defective, recombinant retrovirus
      capable of producing a high level of p16 protein expression (pCLXSN-p16). G418
      resistant stable P16 protein expression cell lines were selected. And the
      biological behaviours of the p16 gene transfected HCC cells were observed.
      RESULTS: Initial in vitro experiments in HCC cell line SNU-449 with loss of p16
      protein expression demonstrated the pCLXSN-p16 treatment significantly inhibited
      cell growth. But there was no treatment effect when the pCLXSN-p16 was used in
      another HCC cell line HepG2.2.15 which has positive p16 protein expression.
      Subsequent study in a nude mouse model demonstrated that the p16 gene transfected
      SNU-449 had a lower succeeding rate in the first time establishment of tumors and
      grew more slowly in the nude mice when compared with non-transfected SNU-449.
      Moreover, the nude mice inoculated with transfected SNU-449 had a longer
      surviving time than those inoculated with non-transfected SNU-449. CONCLUSION:
      Our results show that the p16INK4a gene transfer can inhibit the proliferation
      and reduce the invasion ability of hepatocellular carcinoma.

PMID- 12508358
TI  - Mutation analysis of novel human liver-related putative tumor suppressor gene in
      hepatocellular carcinoma.
AB  - AIM: To find the point mutations meaningful for inactivation of liver-related
      putative tumor suppressor gene (LPTS) gene, a human novel liver-related putative
      tumor suppressor gene and telomerase inhibitor in hepatocellular carcinoma.
      METHODS: The entire coding sequence of LPTS gene was examined for mutations by
      single strand conformation polymorphism (SSCP) assay and PCR products direct
      sequencing in 56 liver cancer cell lines, 7 ovarian cancer and 7 head neck tumor
      cell lines and 70 pairs of HCC tissues samples. The cDNA fragment coding for the
      most frequent mutant protein was subcloned into GST fusion expression vector. The
      product was expressed in E.coli and purified by glutathione-agarose column.
      Telomeric repeat amplification protocol (TRAP) assays were performed to study the
      effect of point mutation to telomerase inhibitory activity. RESULTS: SSCP gels
      showed the abnormal shifting bands and DNA sequencing found that there were 5
      different mutations and/or polymorphisms in 12 tumor cell lines located at exon2,
      exon5 and exon7. The main alterations were A(778)A/G and A(880)T in exon7. The
      change in site of 778 could not be found in HCC tissue samples, while the
      mutation in position 880 was seen in 7 (10 %) cases. The mutation in the site of
      880 had no effect on telomerase inhibitory activity. CONCLUSION: Alterations
      identified in this study are polymorphisms of LPTS gene. LPTS mutations occur in
      HCC but are infrequent and of little effect on the telomerase inhibitory function
      of the protein. Epigenetics, such as methylation, acetylation, may play the key
      role in inactivation of LPTS.

PMID- 12508359
TI  - Application of poly-lactide-co-glycolide-microspheres in the transarterial
      chemoembolization in an animal model of hepatocellular carcinoma.
AB  - AIM: To introduce an animal model of hepatocellular carcinoma (HCC) in ACI-rats,
      and to evaluate the therapeutic effects of Poly-lactide-co-glycolide (Plcg) 
      microspheres in the transarterial chemoembolization (TACE) in this model, as well
      the value of this model in the experiments of interventional therapy. METHODS:
      Subcapsular implantation of a solid Morris Hepatoma 3 924A (1 mm(3)) in the
      livers was carried out in 11 male ACI-rats. The tumor volume (V1) was measured by
      magnetic resonance imaging (MRI) (13 days after implantation). After laparotomy
      and retrograde placement of catheter into the gastroduodenal artery (14 days
      after implantation), the following protocols of interventional treatment were
      performed: (A) mitomycin C+Poly-lactide-co-glycolide (Plcg)-microspheres (n=4);
      (B) 0.9 % NaCl (control group, n=7). 13 days after these therapies the change of
      the tumor volume (V2) was determined by MRI again. RESULTS: The success rate of
      tumor implantation reached to 100 %. The mean tumor volume before TACE (V1) were
      0.082 cm(3) in group A and 0.096 cm(3) in group B respectively. The mean tumor
      volume after TACE (V2) were 0.230 cm(3) in group A and 1.347 cm(3) in group B
      respectively. The mean V2/V1 were 2.860 in group A and 27.120 in group B
      respectively. Compared to the control group (group B), groups A showed a
      significant reduction of tumor growth (P=0.004) in the period of observation.
      CONCLUSION: The growth of liver tumor could be obviously prevented by utilizing
      Plcg-mitomycin-microspheres in TACE in animal model. This rat model of HCC is
      suitable for the experimental studies of interventional therapy.

PMID- 12508360
TI  - Nested case-control study on the risk factors of colorectal cancer.
AB  - AIM: To investigate the risk factors of colon cancer and rectal cancer. METHODS:
      A nested case-control study was conducted in a cohort of 64 693 subjects who
      participated in a colorectal cancer screening program from 1989 to 1998 in
      Jiashan county, Zhejiang, China. 196 cases of colorectal cancer were detected
      from 1990 to 1998 as the case group and 980 non-colorectal cancer subjects,
      matched with factors of age, gender, resident location, were randomly selected
      from the 64 693 cohort as controls. By using univariate analysis and multivariate
      conditional logistic regression analysis, the odds ratio (OR) and its 95 %
      confidence interval (95 %CI) were calculated between colorectal cancer and
      personal habits, dietary factors, as well as intestinal related symptoms.
      RESULTS: The multivariate analysis results showed that after matched with age,
      sex and resident location, mucous blood stool history and mixed sources of
      drinking water were closely associated with colon cancer and rectal cancer, OR
      values for the mucous blood stool history were 3.508 (95 %CI: 1.370-8.985) and
      2.139 (95 %CI: 1.040-4.402) respectively; for the mixed drinking water sources,
      2.387 (95 %CI: 1.243-4.587) and 1.951 (95 %CI: 1.086-3.506) respectively. All
      reached the significant level with a P-value less than 0.05. CONCLUSION: The
      study suggested that mucous blood stool history and mixed sources of drinking
      water were the risk factors of colon cancer and rectal cancer. There was no any
      significant association between dietary habits and the incidence of colorectal
      cancer.

PMID- 12508361
TI  - Design of a ribozyme targeting human telomerase reverse transcriptase and cloning
      of it's gene.
AB  - AIM: To design a hammerhead ribozyme targeting human telomerase reverse
      transcriptase (hTERT) and clone it's gene for future use in the study of tumor
      gene therapy. METHODS: Using the software RNA structure, the secondary structure
      of hTERT mRNA was predicted and the cleavage site of ribozyme was selected. A
      hammerhead ribozyme targeting this site was designed and bimolecular fold between
      the ribozyme and hTERT was predicted. The DNA encoding the ribozyme was
      synthesized and cloned into pGEMEX-1 and the sequence of the ribozyme gene was
      confirmed by DNA sequencing. RESULTS: Triplet GUC at 1742 of hTERT mRNA was
      chosen as the cleavage site of the ribozyme. The designed ribozyme was comprised
      of 22nt catalytic core and 17nt flanking sequence. Computer-aided prediction
      suggested that the ribozyme and hTERT mRNA could cofold into a proper
      conformation. Endonuclease restriction and DNA sequencing confirmed the correct
      insertion of the ribozyme gene into the vector pGEMEX-1. CONCLUSION: This
      fundamental work of successful designing and cloning of an anti-hTERT hammerhead
      ribozyme has paved the way for further study of inhibiting tumor cell growth by
      cleaving hTERT mRNA with ribozyme.

PMID- 12508362
TI  - HBV DNA vaccine with adjuvant cytokines induced specific immune responses against
      HBV infection.
AB  - AIM: To seek for an effective method to improve the immune responses induced by
      DNA vaccine expressing HBV surface antigen (pCR3.1-S) in Balb/c mice (H-2(d)).
      METHODS: The pCR3.1-S plasmid and the eukaryotic expression vectors expressing
      murine IL-2 (pDOR-IL-2) or IL-12 (pWRG3169) were injected into mice
      subcutaneously. The immune responses to pCR3.1-S and the adjuvant effect of the
      cytokines plasmid were studied. Meanwhile the effect of pCR3.1-S on anti
      translated subcutaneous tumor of P815 mastocytoma cells stably expressing HBsAg
      (P815-HBV-S) was also studied. Anti-HBs in serum was detected by enzyme-linked
      immunoadsorbent assay (ELISA) and HBsAg specific cytotoxic T lymphocytes (CTLs)
      activity was measured by (51)Cr release assay. After three weeks of DNA
      immunization, the cells of P815-HBV-S were inoculated into mice subcutaneously
      and the tumor growth was measured every five days. The survival rate and living
      periods of mice were also calculated. RESULTS: After 8 wk DNA immunization, the A
      450 nm values of sera in mice immunized with pCR3.1, pCR3.1-S and pCR3.1-S
      codeliveried with IL-2 or IL-12 plasmids were 0.03+/-0.01, 1.24+/-0.10, 1.98+/
      0.17 and 1.67+/-0.12 respectively. Data in mice codeliveried pCR3.1-S with IL-2
      or IL-12 plasmids were significantly higher than that of mice injected pCR3.1 or
      pCR3.1-S only. The HBsAg specific CTL activities in mice coinjected with pCR3.1-S
      and IL-2 or IL-12 eukaryotic expression vectors were (61.9+/-7.1) % and (73.3+/
      8.8) %, which were significantly higher than that of mice injected with pCR3.1
      (10.1+/-2.1) % or pCR3.1-S (50.5 +/-6.4) %. The HBsAg specific CTL activities in
      mice injected with pCR3.1, pCR3.1-S, pCR3.1-S combined with IL-2 or IL-12
      eukaryotic expression vectors decreased significantly to (3.2+/-0.8) %, (10.6+/
      1.4) %, (13.6+/-1.3) % and (16.9+/-2.3) % respectively after the spleen cells
      were treated by anti-CD8(+) monoclonal antibody, but presented no significant
      change to anti-CD4(+) monoclonal antibody or unrelated to monoclonal antibody.
      The HBV-S DNA vaccine (pCR3.1-S) could evidently inhibit the tumor growth,
      prolong the survival period of mice and improve the survival rate of mice and
      these effects could be improved by IL-12 gene codeliveried. CONCLUSION: HBV DNA
      vaccine has a strong antigenicity in humoral and cellular immunities, which can
      be promoted by plasmid expressing IL-2 or IL-12. CD8+ cells executed the CTL
      activities. DNA vaccine may be useful for both prophylaxis and treatment of HBV
      infection.

PMID- 12508363
TI  - Expression of hepatitis B virus X protein in transgenic mice.
AB  - AIM: To establish a mice model harboring hepatitis B virus x gene (adr subtype)
      for studying the function of hepatitis B virus X protein, a transactivator of
      viral and cellular promoter/enhancer elements. METHODS: Expression vector pcDNA3
      HBx, containing CMV promoter and hepatitis B virus x gene open reading fragment,
      was constructed by recombination DNA technique. Hela cells were cultured in DMEM
      and transfected with pcDNA3-HBx or control pcDNA3 plasmids using FuGENE6
      Transfection Reagent. Expression of pcDNA3-HBx vectors in the transfected Hela
      cells was confirmed by Western blotting. After restriction endonuclease
      digestion, the coding elements were microinjected into male pronuclei of mice
      zygotes. The pups were evaluated by multiplex polymerase chain reaction (PCR) at
      genomic DNA level. The x gene transgenic mice founders were confirmed at protein
      level by Western blotting, immunohistochemistry and immunogold transmission
      electron microscopy. RESULTS: Expression vector pcDNA3-HBx was constructed by
      recombination DNA technique and identified right by restriction endonuclease
      digestion and DNA direct sequencing. With Western blotting, hepatitis X protein
      was detected in Hela cells transfected with pcDNA3-HBx plasmids, suggesting
      pcDNA3-HBx plasmids could express in eukaryotic cells. Following microinjection
      of coding sequence of pcDNA3-HBx, the embryos were transferred to oviducts of
      pseudopregnant females. Four pups were born and survived. Two of them were
      verified to have the HBx gene integrated in their genomic DNA by multiplex PCR
      assay, and named C57-TgN(HBx)SMMU1 and C57-TgN(HBx)SMMU3 respectively. They
      expressed 17KD X protein in liver tissue by Western blotting assay. With the
      immunohistochemistry, X protein was detected mainly in hepatocytes cytoplasm of
      transgenic mice, which was furthermore confirmed by immunogold transmission
      electon microscopy. CONCLUSION: We have constructed the expression vector pcDNA3
      HBx that can be used to study the function of HBx gene in eukaryotic cells in
      vitro. We also established HBx gene (adr subtype) transgenic mice named C57-TgN
      (HBx)SMMU harboring HBx gene in their genome and express X protein in
      hepatocytes, Which might be a valuable animal system for studying the roles of
      HBx gene in hepatitis B virus life cycle and development of hepatocellular
      carcinoma in vivo.

PMID- 12508364
TI  - Changes in serum and histology of patients with chronic hepatitis B after
      interferon alpha-2b treatment.
AB  - AIM: Chronic hepatitis B is a serious health problem. Interferon has long been
      used to treat Chronic hepatitis B. To evaluate the effects of interferon on
      chronic hepatitis B better, we designed the study to investigate the changes in
      sera and liver histology of patients with chronic hepatitis B after interferon
      alpha-2b treatment. METHODS: Twenty-four patients with chronic hepatitis B were
      enrolled in this study. They all received interferon alpha-2b treatment as
      following: 3 million units, i.m. t.i.w., for 18 weeks. Sera of all patients were
      obtained respectively for evaluation of ALT, HBsAg, HBcAg, HBeAg, HBV DNA and
      TIMP-1 before and after interferon treatment, also a liver biopsy pre- and post
      treatment was performed for comparison of HAI, HBsAg, HBcAg, HBeAg, TIMP-1 and
      activated HSC in the liver tissue. RESULTS: Patients who had normalization of
      serum ALT and seroconversion of HBeAg and/or HBV DNA (blot hybridization) after
      treatment were defined as responders. The response rate in this study group was
      37.5 % (7/24). Compared to pretreatment, the serum HBV DNA and TIMP-1 decreased
      significantly (P<0.05), so did the HAI, HBcAg, HBeAg, TIMP-1 and activated HSC
      (P<0.05). CONCLUSION: The significant decrease in HBV DNA in sera, the
      seroconversion of HBeAg, and the decrease of viral expression in liver indicated
      that interferon alpha-2b treatment can inhibit viral replication. The
      normalization of ALT in sera and the improvement of HAI in liver showed that
      interferon alpha-2b can improve the liver histology of patients with chronic
      hepatitis B. At the same time, interferon alpha-2b treatment can reduce the TIMP
      1 in serum and liver and decrease the number of activated HSC, which may
      alleviate or inhibit hepatic fibrosis. Although the response rate was
      unsatisfactory, interferon play a beneficial role on patients with chronic
      hepatitis B in other respects. We still need further studies to improve the
      therapy effects.

PMID- 12508365
TI  - Expression of Lewis(b) blood group antigen in Helicobacter pylori does not
      interfere with bacterial adhesion property.
AB  - AIM: The finding that some Helicobacter pylori strains express Lewis b (Le(b))
      blood group antigen casts a doubt on the role of Le(b) of human gastric
      epithelium being a receptor for H. pylori. The aim of this study was to determine
      if expression of Le(b) in H. pylori interferes with bacterial adhesion property.
      METHODS: Bacterial adhesion to immobilized Le(b) on microtitre plate was
      performed in 63 H. pylori strains obtained from Singapore using in vitro
      adherence assay. Expression of Lewis blood group antigens was determined by ELISA
      assay. RESULTS: Among 63 H. pylori strains, 28 expressed Le(b) antigen. In vitro
      adhesion assay showed that 78.6 % (22/28) of Le(b)-positive and 74.3 % (26/35) of
      Le(b)-negative H. pylori isolates were positive for adhesion to immobilized Le(b)
      coated on microtitre plate (P=0.772). In addition, blocking of H. pylori Le(b) by
      prior incubation with anti-Le(b) monoclonal antibody did not alter the binding of
      the bacteria to solid-phase coated Le(b). CONCLUSION: The present study suggests
      that expression of Le(b) in H. pylori does not interfere with the bacterial
      adhesion property. This result supports the notion that Le(b) present on human
      gastric epithelial cells is capable of being a receptor for H. pylori.

PMID- 12508366
TI  - N-acetylcysteine attenuates alcohol-induced oxidative stress in the rat.
AB  - AIM: There is increasing evidence that alcohol-induced liver damage may be
      associated with increased oxidative stress. We aimed to investigate free-radical
      scavenger effect of n-acetylcysteine in rats intragastrically fed with ethanol.
      METHODS: Twenty-four rats divided into three groups were fed with ethanol (6
      g/kg/day, Group 1), ethanol and n-acetylcysteine (1 g/kg, Group 2), or isocaloric
      dextrose (control group, Group 3) for 4 weeks. Then animals were sacrificed under
      ether anesthesia, intracardiac blood and liver tissues were obtained.
      Measurements were performed both in serum and in homogenized liver tissues.
      Malondialdehyde (MDA) level was measured by TBARS method. Glutathione peroxidase
      (GSH-Px) and superoxide dismutase (SOD) levels were studied by commercial kits.
      Kruskal-Wallis test was used for statistical analysis. RESULTS: ALT and AST in
      Group 1 (154 U/L and 302 U/L, respectively) were higher than those in Group 2 (94
      U/L and 155 U/L) and Group 3 (99 U/L and 168 U/L) (P=0.001 for both). Serum and
      tissue levels of MDA in Group 1 (1.84 nmol/mL and 96 nmol/100 mg-protein) were
      higher than Group 2 (0.91 nmol/mL and 64 nmol/100 mg-protein) and Group 3 (0.94
      nmol/mL and 49 nmol/100 mg-protein) (P<0.001 for both). On the other hand, serum
      GSH-Px level in Group 1 (8.21 U/g-Hb) was lower than Group 2 (16 U/g-Hb) and
      Group 3 (16 U/g-Hb) (P<0.001). Serum and liver tissue levels of SOD in Group 1
      (11 U/mL and 26 U/100 mg-protein) were lower than Group 2 (18 U/mL and 60 U/100
      mg-protein) and Group 3 (20 U/mL and 60 U/100 mg-protein) (P<0.001 for both).
      CONCLUSION: This study demonstrated that ethanol-induced liver damage is
      associated with oxidative stress, and co-administration of n-acetylcysteine
      attenuates this damage effectively in rat model.

PMID- 12508367
TI  - Mechanisms for regulation of gastrin and somatostatin release from isolated rat
      stomach during gastric distention.
AB  - AIM: To investigate the intragastric mechanisms for regulation of gastric
      neuroendocrine functions during gastric distention in isolated vascularly
      perfused rat stomach. METHODS: Isolated vascularly perfused rat stomach was
      prepared, then the gastric lumen was distended with either 5,10 or 15 ml pH7
      isotonic saline during a period of 20 min. During the distention, the axonal
      blocker tetrodotoxin (TTX), the cholinergic antagonist atropine, or the putative
      somatostatin-antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)) were
      applied by vascular perfusion. The releases of gastrin and somatostatin were then
      examined by radioimmunoassay. RESULTS: The graded gastric distention caused a
      significant volume-dependent decrease in gastrin secretion (-183+/-75 (5 ml), 
      385+/-86 (10 ml) and -440+/-85 (15 ml) pg/20 min) and a significant increase of
      somatostatin secretion (260+/-102 (5 ml), 608+/-148 (10 ml) and 943+/-316 (15 ml)
      pg/20 min). In response to 10 ml distention, the infusion of either axonal
      blocker TTX (10(-6) M) or cholinergic blocker atropine (10(-7) M) had a similar
      affect. They both attenuated the decrease of gastrin release by approximately 50
      %, and attenuated the increase of somatostatin release by approximately 40 %. The
      infusion of somatostatin-antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-Thr
      (Bzl)) (10(-6)M) attenuated the decrease of gastrin release by about 60 %.
      Furthermore, combined infusion of the somatostatin-antagonist and atropine
      completely abolished distention-induced inhibition of gastrin release.
      CONCLUSION: The present data suggest that distention of isolated rat stomach
      stimulates somatostatin release via cholinergic and non-cholinergic TTX
      insensitive pathways. Both somatostatin and intrinsic cholinergic pathways are
      responsible for distention-induced inhibition of gastrin release.

PMID- 12508368
TI  - Effects of tetrandrine on calcium and potassium currents in isolated rat
      hepatocytes.
AB  - AIM: To study the effects of tetrandrine (Tet) on calcium release-activated
      calcium current (I(CRAC)), delayed rectifier potassium current (I(K)), and inward
      rectifier potassium currents (I(K1)) in isolated rat hepatocytes. METHODS:
      Hepatocytes of rat were isolated by using perfusion method. Whole cell patch
      clamp techniques were used in our experiment. RESULTS: The peak amplitude of
      I(CRAC) was -508+/-115 pA (n=15), its reversal potential of I(CRAC) was about 0
      mV. At the potential of -100 mV, Tet inhibited the peak amplitude of I(CRAC) from
      -521+/-95 pA to -338+/-85 pA (P<0.01 vs control, n=5), with the inhibitory rate
      of 35 % at 10 micromol/L and from -504+/-87 pA to -247+/-82 pA (P<0.01 vs
      control, n=5), with the inhibitory rate of 49 % at 100 micromol/L, without
      affecting its reversal potential. The amplitude of I(CRAC) was dependent on
      extracellular Ca(2+) concentration. The peak amplitude of I(CRAC) was -205+/-105
      pA (n=3) in tyrode's solution with Ca(2+) 1.8 mmol/L (P<0.01 vs the peak
      amplitude of I(CRAC) in external solution with Ca(2+) 10 mmol/L). Tet at the
      concentration of 10 and 100 micromol/L did not markedly change the peak amplitude
      of delayed rectifier potassium current and inward rectifier potassium current
      (P>0.05 vs control). CONCLUSION: Tet protects hepatocytes by inhibiting I(CRAC),
      which is not related to I(K) and I(K1).

PMID- 12508369
TI  - Influence of intrauterine injection of rat fetal hepatocytes on rejection of rat
      liver transplantation.
AB  - AIM: To investigate the influence of immune tolerance induced by intrauterine
      exposure to fetal hepatocytes on liver transplantation in the adult rat. METHODS:
      LOU/CN rat fetal hepatocytes were injected into the fetuses of pregnant CHN rats
      (14-16 days of gestation). At 7-9 weeks of age, the surviving male rats received
      orthotopic liver transplantation (OLT) from male LOU/CN donors and the survival
      period was observed and monitered by mixed lymphocyte reaction assay and
      cytotoxicity test. RESULTS: (1) A total of 31 pregnant CHN rats with 172 fetuses
      received fetal hepatocytes from LOU/CN rats via intrauterine injection. Among
      them, thirteen pregnant rats showed normal parturition, with 74 neonatal rats
      growing up normally. (2) The mean survival period after OLT in rats with fetal
      exposure to fetal hepatocytes was 32.1+/-3.7 days, which was significantly
      different from the control (11.8+/-2.3 days, P<0.01) in rats without fetal
      induction of immune tolerance. (3) Mixed lymphocyte proliferation assays yielded
      remarkable discrepancies between the groups of rats with- or without fetal
      exposure to fetal hepatocytes, with values of 8,411+/-1,361 and 22,473+/-1,856
      (CPM+/-SD, P<0.01) respectively. (4) Cytotoxicity assays showed values of 21.2+/
      6.5 % and 64.5+/-7.2 % (P<0.01) in adult rats with or without fetal induction of
      immune tolerance. CONCLUSION: Intrauterine injection of fetal hepatocytes into
      rat fetuses can prolong the survival period of liver transplant adult male rats
      recipients, inducting immune tolerance in OLT.

PMID- 12508370
TI  - Functional changes of dendritic cells derived from allogeneic partial liver graft
      undergoing acute rejection in rats.
AB  - AIM: To investigate functional change of dendritic cells (DCs) derived from
      allogeneic partial liver graft undergoing acute rejection in rats. METHODS:
      Allogeneic (SD rat to LEW rat) whole and 50 % partial liver transplantation were
      performed. DCs from liver grafts 0 hr and 4 days after transplantation were
      isolated and propagated in the presence of GM-CSF in vitro. Morphological
      characteristics of DCs propagated for 4 days and 10 days were observed by
      electron microscopy. Phenotypical features of DCs propagated for 10 days were
      analyzed by flow cytometry. Expression of IL-12 protein and IL-12 receptor mRNA
      in DCs propagated for 10 days was also measured by Western blotting and
      semiquantitative RT-PCR, respectively. Histological grading of rejection were
      determined. RESULTS: Allogeneic whole liver grafts showed no features of
      rejection at day 4 after transplantation. In contrast, allogeneic partial liver
      grafts demonstrated moderate to severe rejection at day 4 after transplantation.
      DCs derived from allogeneic partial liver graft 4 days after transplantation
      exhibited typical morphological characteristics of DC after 4 days' culture in
      the presence of GM-CSF. DCs from allogeneic whole liver graft 0 hr and 4 days
      after transplantation did not exhibit typical morphological characteristics of DC
      until after 10 days' culture in the presence of GM-CSF. After 10 days'
      propagation in vitro, DCs derived from allogeneic whole liver graft exhibited
      features of immature DC, with absence of CD40, CD80 and CD86 surface expression,
      and low levels of IL-12 proteins (IL-12 p35 and IL-12 p40) and IL-12 receptor (IL
      12Rbeta(1) and IL-12Rbeta(2)) mRNA, whereas DCs from allogeneic partial liver
      graft 4 days after transplantation displayed features of mature DC, with high
      levels of CD40, CD80 and CD86 surface expression, and as a consequence, higher
      expression of IL-12 proteins (IL-12 p35 and IL-12 p40) and IL-12 receptors (IL
      12Rbeta1 and IL-12Rbeta2) mRNA than those of DCs both from partial liver graft 0
      hr and whole liver graft 4 days after transplantation (P<0.001) was observed.
      CONCLUSION: DCs derived from allogeneic partial liver graft undergoing acute
      rejection display features of mature DC.

PMID- 12508371
TI  - Cloning and analysing the up-regulated expression of transthyretin-related gene
      (LR1) in rat liver regeneration following short interval successive partial
      hepatectomy.
AB  - AIM: Cloning and analysing the up-regulated expression of transthyretin-related
      gene following short interval successive partial hepatectomy (SISPH) to elucidate
      the mechanism of differentiation, division, dedifferentiation and
      redifferentiation in rat liver regeneration (LR). METHODS: Lobus external
      sinister and lobus centralis sinister, lobus centralis, lobus dexter, lobus
      candatus were removed one by one from rat liver at four different time points 4,
      36, 36 and 36 hr (total time: 4 hr, 40 hr, 76 hr, 112 hr) respectively.
      Suppression subtractive hybridization (SSH) was carried out by using normal rat
      liver tissue as driver and the tissue following short interval successive partial
      hepatectomy (SISPH) as tester to construct a highly efficient forward-subtractive
      cDNA library. After screening, an interested EST fragment was selected by SSH and
      primers were designed according to the sequence of the EST to clone the full
      length cDNA fragment using RACE (rapid amplification of cDNA end). Homologous
      detection was performed between the full-lenth cDNA and Genbank. RESULTS: Forward
      suppression subtractive hybridization (FSSH) library between 0 h and 112 h
      following SISPH was constructed and an up-regulated full-length cDNA (named LR1),
      which was related with the transthyretin gene, was cloned by rapid amplification
      of cDNA end. It was suggested that the gene is involved in the cellular
      dedifferentiation in LR following SISPH. CONCLUSION: Some genes were up-regulated
      in 112 h following SISPH in rat. LR(1) is one of these up-regulated expression
      genes which may play an important role in rat LR.

PMID- 12508372
TI  - Effects of pentoxifylline on the hepatic content of TGF-beta1 and collagen in
      Schistosomiasis japonica mice with liver fibrosis.
AB  - AIM: To study the effects of pentoxifylline (PTX) on the content of hepatic TGF
      beta1, type I and type III collagen in schistosomiasis japonica mice with liver
      fibrosis and its mechanism of anti-fibrosis. METHODS: Forty mice with
      schistosomiasis were divided into four groups: one group as control without any
      treatment, other three were treated with Praziquantel 500 mg/(kg x d)for 2 d,
      high dose PTX 360 mg/(kg x d) for 8 wk, and low dose PTX 180 mg/(kg x d) for 8 wk
      respectively. Immunohistochemical technique and multimedia color pathographic
      analysis system were applied to observe the content change of hepatic TGF-beta1,
      type I and type III collagen in schistosomiasis japonica mice with liver fibrosis
      before and after PTX treatment. RESULTS: Effects of PTX on the content change of
      hepatic TGF-beta1, type I and type III collagen in schistosomiasis japonica mice
      with liver fibrosis were related to the dosage of PTX, high dose PTX treated
      group could significantly reduce the content of TGF-beta1 (0.709+/-0.111), type I
      (0.644+/-0.108) and type III (0.654+/-0.152) collagen compared with those of
      control group (0.883+/-0.140, 0.771+/-0.156, 0.822+/-0.129) with statistical
      significance (P<0.05). Low dose PTX could also reduce the hepatic content of TGF
      beta1 (0.752+/-0.152), type I (0.733+/-0.117) and type III (0.788+/-0.147)
      collagen, but without statistical significance (P>0.05). Both high dose and low
      dose PTX groups have significant differences on the content of TGF-beta1, type I
      and type III collagen (P<0.05, P<0.05, P<0.01, respectively). CONCLUSION: High
      dose of PTX treatment could reduce the content of hepatic TGF-beta1, type I and
      type III collagen significantly in schistosomiasis japonica mice with liver
      fibrosis, and thus plays its role of antifibrosis.

PMID- 12508373
TI  - Effects of Tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and
      liver of rats with acute pancreatitis.
AB  - AIM: Available experimental evidence from both clinical and animal models shows
      that both Chinese medicines tetrandine (Tet) and Qing Yi Tong (QYT) have positive
      treatment effects on acute pancreatitis (AP). This investigation was conducted to
      explore the treatment mechanisms of Tet and QYT on AP at the molecular level and
      thereby explain their therapeutic affects. It included an investigation of the
      effects of these drugs on gene expression of both intercellular adhesion molecule
      1 (ICAM-1) and superoxide dismutase (Mn-SOD and Cu, Zn-SOD) in a rat model with
      AP. METHODS: AP in the test rats was induced by subjecting them to laparotomy
      followed by a retrograde injection of 4 % sodium taurocholate into the bilio
      pancreatic duct. The test rats with AP were divided into three groups. One was
      treated with Tet, one with QYT, and one with normal saline solution. The sham
      operated control group (SO) rats were only subjected to laparotomy. They were
      given no further treatment. For the Tet group, Tet was injected
      intraperitoneally, and for the QYT group, QYT was given with a nose-gastric
      catheter. These procedures were done at both 10 min and 5 h after AP induction.
      The levels of ICAM-1 mRNA expression and of SOD (Mn-SOD and Cu, Zn-SOD) mRNA
      expression in the pancreas and liver tissues were measured by RT-PCR at 1, 5, and
      10 h after AP induction. RESULTS: When compared with the SO group during the
      observation time, rats with AP showed a higher expression of ICAM and a lower
      expression of Mn-SOD in both pancreas and liver tissues, and a lower expression
      of Cu, Zn-SOD in the pancreas. Tet treatment attenuated changes in the expression
      of both ICAM-1, and SOD (Mn-SOD and Cu, Zn-SOD) to a significant degree. A
      similar effect on the expression of SOD (Mn-SOD and Cu, Zn-SOD) was also found in
      the QYT group, but no obvious suppressive effect on ICAM-1 expression was
      observed. CONCLUSION: The results of this study suggest that one of the main
      mechanisms of Tet and QYT in treating AP is to enhance anti-oxidation of the
      body. The results also suggest that the anti-inflammatory effect of Tet is
      involved in the reduction of ICAM-1 expression. This explains why Tet and QYT are
      beneficial in treating AP.

PMID- 12508374
TI  - Relationship between overexpression of NK-1R, NK-2R and intestinal mucosal damage
      in acute necrotizing pancreatitis.
AB  - AIM: To study the expression of neurokinin-1 receptor (NK-1R) and neurokinin-2
      receptor (NK-2R) in distal ileum of acute necrotizing pancreatitis (ANP) and to
      evaluate the relationship between expression of these two receptors and
      intestinal mucosal damage. METHODS: A total of 130 adult Sprague-Dawley rats were
      randomly divided into two groups: the rats in ANP group (n=80) were induced by
      the retrograde intraductal infusion of 30 g.L(-1) sodium taurocholate. And the
      rats in normal control group (n=50) received laparotomy only. Sacrifices were
      made 6 h, 12 h, 24 h and 48 h later in ANP and normal control group after
      induction respectively. Intestinal mucosal permeability was studied by
      intrajejunal injection of 1.5 mCi radioactive isotope (99m)Tc-diethlene triamine
      pentacetic acid (DTPA) and the radioactivity of (99m)Tc-DTPA content in urine was
      measured 6 h, 12 h, 24 h and 48 h after induction. Then the pancreas and
      intestine were prepared for pathology. Reverse transcription polymerase chain
      reaction (RT-PCR) was used to determine the mRNA expression of NK-1R and NK-2R,
      and Western blot was used to investigate the protein level of NK-1R and NK-2R.
      RESULTS: In ANP rats, serious histologic damages in intestinal mucosa were
      observed, and the radioactivity of (99m)Tc-DTPA in urine increased significantly
      in the ANP group. RT-PCR revealed that NK-1R and NK-2R mRNA level was
      overexpressed in the distal ileum of ANP as compared with the normal control
      group. Western blot discovered stronger NK-1R (14-fold increase) and NK-2R (9
      fold increase) immunoreactivity in the intestinal mucosa of ANP rats. Moreover,
      the overexpression of NK-1R was associated with mucosal pathological score
      (r=0.77, P<0.01) and intestinal permeability (r=0.68, P<0.01) in ANP rats.
      CONCLUSION: NK-1R and NK-2R contribute to disrupted neuropeptides loop balance,
      deteriorate intestinal damage, and are involved in pathophysiological changes in
      ANP.

PMID- 12508375
TI  - Effect of oxytocin on contraction of rabbit proximal colon in vitro.
AB  - AIM: To investigate the effects of oxytocin (OT) on isolated rabbit proximal
      colon and its mechanism. METHODS: Both longitudinal muscle (LM) and circular
      muscle (CM) were suspended in a tissue chamber containing 5 mL Krebs solution (37
      degrees ), bubbled continuously with 950 mL x L(-1) O(2) and 50 mL x L(-1) CO(2).
      Isometric spontaneous contractile responses to oxytocin or other drugs were
      recorded in circular and longitudinal muscle strips. RESULTS: OT (0.1 U x L(-1))
      failed to elicit significant effects on the contractile activity of proximal
      colonic smooth muscle strips (P>0.05). OT (1 to 10 U x L(-1)) decreased the mean
      contractile amplitude and the contractile frequency of CM and LM. Hexamethonium
      (10 micromol x L(-1)) partly blocked the inhibition of oxytocin (1 U x L(-1)) on
      the contractile frenquency of CM. N(omega))-nitro-L-arginine-methylester (L-NAME,
      1 micromol x L (-1)), progesterone (32 micromol x L(-1)) and estrogen (2.6
      micromol x L(-1)) had no effects on OT-induced responses. CONCLUSION: OT inhibits
      the motility of proximal colon in rabbits. The action is partly relevant with N
      receptor, but irrelevant with that of NO, progesterone or estrogen.

PMID- 12508376
TI  - A new cytokine: the possible effect pathway of methionine enkephalin.
AB  - AIM: To investigate experimentally the effects of methionine enkephalin on signal
      transduction of mouse myeloma NS-1 cells. METHODS: The antigen determinate of
      delta opioid receptor was designed in this lab and the polypeptide fragment of
      antigen determinate with 12 amino acids residues was synthesized. Monoclonal
      antibody against this peptide fragment was prepared. Proliferation of Mouse NS-1
      cells treated with methionine enkephalin of 1 x 10(-6) mol x L(-1) was observed.
      The activities of protein kinase A (PKA) and protein kinase C (PKC) were measured
      and thereby the mechanism of effect of methionine enkephalin was postulated.
      RESULTS: The results demonstrated that methionine enkephalin could enhance the
      proliferation of NS-1 cells and the effect of methionine enkephalin could be
      particularly blocked by monoclonal antibody. The activity of PKA was increased in
      both cytosol and cell membrane. With reference to PKC, the intracellular activity
      of PKC in NS-1 cells was elevated at 1 x 10(-7) mol x L(-1) and then declined
      gradually as the concentration of methionine enkephalin was raised. The effects
      of methionine enkephalin might be reversed by both naloxone and monoclonal
      antibody. CONCLUSION: Coupled with the findings, it indicates that the signal
      transduction systems via PKA and PKC are involved in the effects of methionine
      enkephalin by binding with the traditional opioid receptors,and therefore
      resulting in different biological effects.

PMID- 12508377
TI  - Is analysis of lower esophageal sphincter vector volumes of value in diagnosing
      gastroesophageal reflux disease?
AB  - AIM: With successful surgical treatment of gastroesophageal reflux disease
      (GERD), there is interest in understanding the anti-reflux barrier and its
      mechanisms of failure. To date, the potential use of vector volumes to predict
      the DeMeester score has not been adequately explored. METHODS: 627 patients in
      the referral database received esophageal manometry and ambulatory 24-hour pH
      monitoring. Study data included LES resting pressure (LESP), overall LES length
      (OL) and abdominal length (AL), total vector volume (TVV) and intrabdominal
      vector volume (IVV). RESULTS: In cases where LESP, TVV or IVV were all below
      normal, there was an 81.4 % probability of a positive DeMeester score. In cases
      where all three were normal, there was an 86.9 % probability that the DeMeester
      score would be negative. Receiver-operating characteristics (ROC) for LESP, TVV
      and IVV were nearly identical and indicated no useful cut-off values. Logistic
      regression demonstrated that LESP and IVV had the strongest association with a
      positive DeMeester score; however, the regression formula was only 76.1 %
      accurate. CONCLUSION: While the indices based on TVV, IVV and LESP are more
      sensitive and specific, respectively, than any single measurement, the
      measurement of vector volumes does not add significantly to the diagnosis of
      GERD.

PMID- 12508378
TI  - Role of NF-kB in multiple organ dysfunction during acute obstructive cholangitis.
AB  - AIM: To elucidate the role of NF-kB activation in the development of multiple
      organ dysfunction (MOD) during acute obstructive cholangitis (AOC) in rats.
      METHODS: Forty-two Wistar rats were divided into three groups: the AOC group, the
      group of bile duct ligation (BDL group), and the sham operation group (SO group).
      All the animals in the three groups were killed in the 6th and 48th hour after
      operation. Morphological changes of vital organs were observed under light and
      electron microscopy. NF-kB activation was determined with Electrophoretic
      Mobility Shift Assay (EMSA). Arterial blood gas analyses and the serum levels of
      lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen
      (BUN) and creatinine were performed. The concentrations of TNF-alpha and IL-6 in
      plasma were also measured. RESULTS: The significant changes of histology and
      ultrastructure of vital organs were observed in AOC group. By contrast, in BDL
      group, all the features of organs damage were greatly reduced. Expression of NF
      kB activation in various tissues increased in AOC group when compared to other
      two groups. At 6 h, the arterial pH in three groups was 7.52+/-0.01, 7.46+/-0.02,
      and 7.45+/-0.02, and the blood pCO(2) was 33.9+/-0.95 mmHg, 38.1+/-0.89 mmHg,
      38.9+/-0.94 mmHg, there was difference in three groups (P<0.05). At 48 h, the
      blood pH values in three groups was 7.33+/-0.07, 7.67+/-0.04, and 7.46+/-0.03,
      and blood HCO(3)(-) was 20.1+/-1.29 mmol x L(-1), 26.7+/-1.45 mmol x L(-1) and
      27.4+/-0.35 mmol x L(-1), there was also difference in three groups (P<0.05). In
      AOC group, Levels of LDH, ALT, BUN and creatinine were 1,6359.9+/-2,278.8 nkat x
      L(-1), 5,796.2+/-941.9 nkat.L(-1), 55.7+/-15.3 mg/dl, and 0.72+/-0.06 mg/dl,
      which were higher than in SO group (3,739.1+/- 570.1 nkat x L(-1), 288.4+/-71.7
      nkat x L(-1), 12.5+/-2.14 mg/dl, and 0.47+/-0.03 mg/dl) (P<0.05). Levels of
      plasma TNF-alpha and IL-6 in AOC at 48 h were 429+/-56.62 ng x L(-1) and 562+/-57
      ng x L(-1), which increased greatly when compared to BDL group (139+/-16 ng x L(
      1), 227+/-43 ng x L(-1)) and SO group (74+/-10 ng x L(-1), 113+/-19 ng x L(-1))
      (P<0.05). CONCLUSION: The pathological damages and the NF-kB activation of many
      vital organs excised during AOC. These findings have an important implication for
      the role of NF-kB activation in MOD during AOC.

PMID- 12508379
TI  - Proliferative activity of bile from congenital choledochal cyst patients.
AB  - AIM: To explore the potential carcinogenicity of bile from congenital choledochal
      cyst (CCC) patients and the mechanism of the carcinogenesis in congenital
      choledochal cyst patients. METHODS: 20 bile samples from congenital choledochal
      cyst patients and 10 normal control bile samples were used for this study. The
      proliferative effect of bile was measured by using Methabenzthiazuron (MTT)
      assay; Cell cycle and apoptosis were analyzed by using flow cytometry (FCM), and
      the PGE(2) levels in the supernatant of cultured cholangiocarcinoma cells were
      quantitated by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: CCC bile
      could significantly promote the proliferation of human cholangiocarcinoma QBC939
      cells compared with normal bile (P=0.001) and negative control group (P=0.002),
      and the proliferative effect of CCC bile could be abolished by addition of
      cyclooxygenase-2 specific inhibitor celecoxib (20 microM). The QBC939 cells
      proliferative index was increased significantly after treated with 1 % bile from
      CCC patient (P=0.008) for 24 h, the percentage of S phase (29.48+/-3.27)% was
      increased remarkably (P<0.001) compared with normal bile (11.72+/-2.70) %, and
      the percentage of G0/G1 phase (54.19+/-9.46) % was decreased remarkably (P=0.042)
      compared with normal bile (69.16+/-10.88) %, however, bile from CCC patient had
      no significant influence on apoptosis of QBC939 cells (P=0.719). CONCLUSION: Bile
      from congenital choledochal cyst patients can promote the proliferation of human
      cholangiocarcinoma QBC939 cells via COX-2 and PGE(2) pathway.

PMID- 12508380
TI  - K-ras gene mutation in the diagnosis of ultrasound guided fine-needle biopsy of
      pancreatic masses.
AB  - AIM: To investigate the utility of K-ras mutation analysis of ultrasound guided
      fine-needle aspirate biopsy of pancreatic masses. METHODS: Sixty-six ultrasound
      guided fine-needle biopsies were evaluated by cytology, histology and k-ras
      mutation. The mutation at codon 12 of the k-ras oncogene was detected by
      artificial restriction fragment length polymorphisms using Bst NI approach.
      RESULTS: The presence of malignant cells was reported in 40 of 54 pancreatic
      carcinomas and K-ras mutations were detected in 45 of the 54 FNABs of pancreatic
      carcinomas. The sensitivity of cytology and k-ras mutation were 74 % and 83 %,
      respectively. The specialty of cytology and k-ras mutation were both 100 %. The
      sensitivity and specialty of k-ras mutation combined with cytology were 83 % and
      100 %, respectively. CONCLUSION: High diagnostic accuracy with acceptable
      discomfort of FNAB make it useful in diagnosis of pancreatic carcinoma.
      Ultrasound guided fine-needle biopsy is a safe and feasible method for diagnosing
      pancreatic cancer. Pancreatic carcinoma has the highest K-ras mutation rate among
      all solid tumors. The mutation rate of k-ras is about 80-100 %. The usage of
      mutation of codon 12 of k-ras oncogene combined with cytology is a good
      alternative for evaluation of pancreatic masses.

PMID- 12508381
TI  - Balancing bones and bucks among new glucocorticoid users.

PMID- 12508382
TI  - HLA studies in psoriatic arthritis: current situation and future needs.

PMID- 12508383
TI  - Psychosocial factors in diffuse upper limb disorder.

PMID- 12508384
TI  - Reduced chemokine and matrix metalloproteinase expression in patients with
      rheumatoid arthritis achieving remission.
AB  - OBJECTIVE: To quantify the changes in synovial expression of mediators of
      macrophage chemotaxis, matrix degradation, and macrophage infiltration in the
      synovial membrane of patients with rheumatoid arthritis (RA) achieving American
      College of Rheumatology (ACR) defined remission and radiological arrest. METHODS:
      Knee synovial biopsies were taken from a selected group of 18 patients with RA
      before and after treatment and immunostained with antibodies specific for CD68;
      the chemokines macrophage inflammatory protein (MIP)-1a and monocyte
      chemoattractant protein (MCP)-1; matrix metalloproteinases (MMP-1 and 3) and
      their inhibitors, the tissue inhibitors of metalloproteinases (TIMP-1 and 2); as
      well as isotype-specific negative controls. Immunostaining was quantified using a
      computer assisted color video image analysis system. Radiographs were performed
      before and after treatment and the Larsen score determined. Patients were
      arbitrarily divided into 2 groups: the radiological arrest group (defined as
      change in Larsen score pound 5 from baseline) and radiological progressors
      (defined as change in Larsen score > 5). Patients were classified according to
      ACR response criteria. RESULTS: In the 8 patients who achieved ACR defined
      remission, there were tendencies toward reductions in the synovial lining layer
      (LL) expression of MIP-1a by 36% (p = 0.1) and MCP-1 by 48% (p = 0.1).
      Significant reductions occurred in the expression of MMP-1, by 53% in the LL (p =
      0.008) and 59% in synovial sublining layer (SL) (p = 0.02) and MMP-3, by 76% in
      LL (p = 0.02), and 72% in SL (p = 0.008), but not in TIMP expression. In this
      group of patients there were reductions in MMP:TIMP ratios, in particular the MMP
      1:TIMP-1 ratio in the LL (p = 0.05), MMP-3:TIMP-1 ratio in the LL (p = 0.05) and
      SL (p = 0.008), and MMP-3:TIMP-2 ratio in the LL (p = 0.04) and SL (p = 0.08). In
      this group of patients CD68+ macrophage infiltration was significantly reduced in
      the LL by 59% (p = 0.008) and in the SL by 52% (p = 0.008), which corresponded
      with the reductions in chemokine expression. In the remaining 10 patients who did
      not achieve full remission there were no significant changes in the variables
      studied. In the group achieving ACR 50% or 70% response there was a reduction in
      CD68 expression that approached significance (p = 0.06 in LL and SL), but there
      was no significant change in the other variables. There were no significant
      changes in the patients with an ACR 20% response. In the radiological arrest
      group (12 patients) there was a 41% reduction in LL expression of MIP-1a (p =
      0.05) and MMP-1 (p = 0.06). Reductions in MMP:TIMP expression were also noted, in
      particular in MMP-1:TIMP-1 expression in the LL (p = 0.04) and MMP-3:TIMP-1 in
      the SL (p = 0.01). There were corresponding reductions in CD68 expression by 49%
      (p = 0.009) in LL and by 42% (p = 0.0005) in SL. In the radiological progressors
      (6 patients) there were no significant reductions in mediator expression.
      CONCLUSION: In RA, ACR defined remission is associated with reductions in MMP-1
      and 3 expression, with a corresponding reduction in macrophage infiltration and a
      tendency to reduction in MIP-1a expression. Radiological arrest is associated
      with reductions in MMP-1 expression, and significant reductions in macrophage
      infiltration, MIP-1 expression, and MMP:TIMP ratio.

PMID- 12508385
TI  - Synergistic effect on the attenuation of collagen induced arthritis in tumor
      necrosis factor receptor I (TNFRI) and interleukin 6 double knockout mice.
AB  - OBJECTIVE: To evaluate any additive effect on attenuation of collagen induced
      arthritis (CIA) in tumor necrosis factor receptor I (TNFRI) and interleukin 6 (IL
      6) double knockout (DKO) mice. METHODS: CIA was induced in wild-type (Wt), TNFRI
      knockout (TNFRIKO), IL-6 knockout (IL-6KO), and DKO mice. Comparative studies
      were performed among these different mouse genotypes observing clinical
      (incidence, arthritis score), histological, radiologic, and immunological
      aspects. RESULTS: More than 90% of the Wt, TNFRIKO, and IL-6KO mice developed
      definite CIA, while only 20% of the DKO mice did so. Severity of arthritis,
      indicated by the arthritis score, was significantly reduced in both the TNFRIKO
      and IL-6KO mice compared with the Wt mice. Moreover, the severity of arthritis in
      the DKO mice was significantly reduced compared with each single KO mouse (by
      arthritis scores; DKO vs TNFRIKO, IL-6KO mice, p < 0.05). In addition,
      histological and radiologic changes were also significantly reduced in the DKO
      mice compared with each single KO mouse (by histological and radiologic scores;
      DKO vs TNFRIKO, IL-6KO mice, p < 0.05 and p < 0.01 respectively). In
      immunological studies, serum anti-type II collagen (anti-CII) antibody
      concentrations were significantly decreased in the DKO mice compared with each
      single KO mouse (DKO vs TNFRIKO, IL-6KO mice, p < 0.01). CONCLUSION: Simultaneous
      blockade of TNFRI and IL-6 showed synergistic rather than additive effects on the
      attenuation of CIA. Combinations of anti-TNF-a and anti-IL-6 therapy may provide
      clinical benefits for treatment of rheumatoid arthritis compared with therapy
      against each single cytokine.

PMID- 12508386
TI  - Pretreatment cytokine profiles of peripheral blood mononuclear cells and serum
      from patients with rheumatoid arthritis in different american college of
      rheumatology response groups to methotrexate.
AB  - OBJECTIVE: To determine the role of putative target cytokines for methotrexate
      (MTX) treatment in patients with rheumatoid arthritis (RA) as predictors for
      treatment outcome. METHODS: Fifty consecutive patients with RA were characterized
      according to demographic and disease associated features and followed
      prospectively before and after 6 months of treatment with MTX. Before starting
      MTX treatment, serum was obtained from each patient and peripheral blood
      mononuclear cells (PBMC) were isolated. PBMC were cultured 2 days under resting
      conditions, and interleukin 1 receptor antagonist (IL-1ra), IL-1beta, soluble
      tumor necrosis factor receptor p55+75 (sTNFR p55+p75), and TNF-a release into
      cell culture supernatants and corresponding serum cytokine levels were determined
      by specific ELISA. Constitutive production and circulating levels of cytokines
      and cytokine inhibitors were correlated to the clinical response after 6 months
      of MTX treatment, and patients were categorized into 4 different groups according
      to the American College of Rheumatology (ACR) response criteria (ACR < 20, 20-50,
      50-70, > 70% improvement from baseline). RESULTS: Good (ACR 50-70) or excellent
      (ACR > 70) responses to MTX treatment were seen in groups of patients with a
      higher proportion of males (25 and 43%) associated with a significantly lower
      ratio of IL-1ra/IL-1beta (p < 0.00001) constitutively produced by PBMC (ratio <
      100) compared with nonresponding (ACR < 20) patients (males 7.7%; ratio > 100).
      The ratios in 3 female poor responders (ACR 20-50) were in between. The decreased
      ratios of IL-1ra/IL-1beta in most good and excellent responders were due to an
      enhanced constitutive IL-1beta release from PBMC (p < 0.004) compared to the
      groups of non or poor responders. Much less pronounced, there was a slightly
      significant increase of sTNFR p55 shedding from PBMC and increase of sTNFR p75
      serum levels in good and excellent responders (both p < 0.02). In contrast, there
      were no intergroup differences regarding constitutive IL-1ra release, sTNFR p75
      shedding, and IL-1ra and sTNFR p55 serum levels and various demographic and
      disease associated characteristics of patients. CONCLUSION: Determination of
      cellularly produced IL-1beta and even more of the IL-1ra/IL-1beta synthesis in
      PBMC may be useful to predict the outcome of RA patients undergoing treatment
      with MTX and may characterize a subset of RA that is more responsive to IL-1
      directed therapeutic interventions.

PMID- 12508387
TI  - Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine whether the risk for cardiovascular and/or
      cerebrovascular disease (CCVD) is increased in rheumatoid arthritis (RA) compared
      to osteoarthritis (OA), a disease not known to be associated with increased CCVD.
      METHODS: In July 1999, a survey was administered to a sample of 11,572 patients
      (9,093 with RA, 2479 with OA) from the practices of 709 US community-based
      rheumatologists. Patients reported past and current myocardial infarction (MI),
      stroke (cerebrovascular accident, CVA), and lifetime congestive heart failure
      (CHF), and also provided demographic and clinical information. To estimate the
      impact of recall bias, medical records were obtained and reviewed for a 50%
      random sample of the patients reporting CCVD events, with 95% of CCVD reported
      events confirmed by record review. RESULTS: Patients with RA and OA differed
      across all demographic variables. In addition, each variable was significantly
      associated with MI, CHF, and CVA outcomes. Logistic regression was performed to
      measure the associations of these outcomes with RA as compared to OA, adjusting
      for age, sex, education level, smoking, income, hypertension, and body mass
      index. Compared with OA, patients with RA had the following increased risks: for
      current MI [odds ratio (OR), 95% confidence interval (95% CI)] 2.14, (1.48,
      3.09), lifetime MI 1.28 (1.24, 1.33), CHF 1.43 (1.28, 1.59), current CVA 1.70
      (1.29, 2.24), and lifetime CVA 1.005 (0.931, 1.196). The adjusted current and
      lifetime prevalences of MI were 0.76 and 4.14% for RA versus 0.35 and 3.23%
      respectively for OA; 0.86 and 3.02% (RA) versus 0.50 and 3.03% (OA) for CVA; and
      for lifetime CHF, 2.34% (RA) versus 1.64% (OA), respectively. CONCLUSIONS: RA is
      associated with an increased risk for CCVD morbidity due to MI, CHF, and probably
      for CVA, and may be an independent risk factor for these events.

PMID- 12508388
TI  - Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid
      arthritis.
AB  - OBJECTIVE: To screen for potential efficacy and assess the feasibility of
      intravenous (IV) doxycycline as a treatment for rheumatoid arthritis (RA).
      METHODS: The study was a (stratified, block) randomized, double blind, 12 week,
      pilot trial of IV doxycycline 300 mg/day versus identical appearing IV placebo
      given over 2 h for 14 days. The primary comparison was to a hypothesized placebo
      rate of 20% as described by Paulus. If a total of 14 consecutive subjects
      receiving doxycycline treatment did not respond, it would be considered futile to
      proceed to a Phase III trial. We planned a placebo group of 14 subjects to verify
      the placebo response rate and estimate sample size required for a definitive
      Phase III trial, if such a trial was warranted based on the pilot study. American
      College of Rheumatology (ACR) RA response criteria were used. After 23 subjects
      entered, the study was closed due to recruitment difficulties. RESULTS: At
      baseline, mean (SD) tender joint count was 37 (11.9), swollen joint count 30
      (9.6), morning stiffness 317 (319) min, and erythrocyte sedimentation rate 72
      mm/h (27.5). Randomization resulted in 10 subjects receiving doxycycline and 13
      receiving placebo. Treatment was stopped in 8 subjects: in 6, treatment was
      ineffective (one taking doxycycline, 5 placebo), and in 2, rashes occurred (one
      taking doxycycline, one placebo). Only one subject met ACR response criteria in
      the doxycycline group and none in the placebo group. Having no responders in the
      placebo group was consistent with placebo response rate of 20% or less. Several
      patients required peripherally inserted central catheters for venous access.
      CONCLUSION: The efficacy of IV doxycycline as a treatment for RA could not be
      ruled out. However, as the proportion of responders was small, it is unlikely
      that potential efficacy of IV doxycycline would outweigh potential disadvantages
      of IV administration.

PMID- 12508389
TI  - Patient compliance in rheumatoid arthritis, polymyalgia rheumatica, and gout.
AB  - OBJECTIVE: (1) To explore patient compliance with prescribed drug regimens in the
      setting of usual care for outpatients with rheumatoid arthritis (RA), gout, and
      polymyalgia rheumatica (PMR) by utilizing electronic medication event monitors
      (MEMS(R)) to register openings of the medication package. (2) To examine the
      influence of disease, frequency of intake of the drug, and class of drug on
      compliance. (3) To explore the influence of demographic factors, quality of life
      measures, coping, health status, and functional ability as potential predictors
      of patient compliance. METHODS: A total of 127 consenting consecutive patients
      were enrolled: 81 patients with RA, 33 taking nonsteroidal antiinflammatory drugs
      (13 diclofenac TID and 20 naproxen BID) and 48 taking disease modifying
      antirheumatic drugs [25 sulfasalazine (SSZ) BID and 23 methotrexate (MTX) once
      weekly]; 17 patients with PMR starting with prednisolone QD; and 29 patients with
      gout starting with colchicine (12, QD) or starting with uric acid lowering agents
      (17, QD). All patients received first prescriptions and were instructed to take
      the medication as prescribed. Followup was 6 months (gout 12 mo). All patients
      were aware of the monitoring capability of the package. At baseline a series of
      questionnaires was completed. We summarized the dosing histories as "taking
      compliance" (percentage of total prescribed doses taken), "correct dosing"
      (percentage of doses taken as prescribed), and "timing compliance" (percentage of
      doses taken within +/- 25% of prescribed interdose intervals). RESULTS: A total
      of 26,685 days (> 73 patient-years) were monitored. Compliance expressed as
      "taking compliance," mean (95% CI), "correct dosing," mean (95% CI), and "timing
      compliance," mean (95% CI) are: naproxen: 82% (75-90), 68% (57-80), 48% (34-61);
      diclofenac: 77% (61-93), 67% (47-87), 39% (21-57); MTX: 107% (98-117), 81% (75
      87), 83% (76-90); SSZ: 72% (60-84), 55% (44-67), 25% (18-33); prednisolone: 96%
      (89-102), 88% (83-92), 82% (74-89); colchicine: 65% (48-81), 44% (26-62), 32% (18
      46); and uric acid lowering agents: 84% (76-92), 74% (63-85), 65% (52-79). Missed
      doses occurred more frequently than taking of extra doses: in RA, on 10% of all
      monitored days there was no evidence of dosing, while on 3% of all monitored days
      extra doses were taken. In PMR and gout these data are 10% and 4%, and 15% and
      7%, respectively. We observed a decline of compliance over time in all study
      medication groups. Multiple regression analyses showed that the class of
      medication (symptom modifying or disease controlling), the dosing frequency, the
      patient's sex, coping pattern (avoidance, passive reaction pattern, and
      expression of emotions), and the overall health (total Nottingham Health Profile
      score) together explained 67% of the variance in taking compliance (adjusted R2)
      (p = 0.002). CONCLUSION: Studying patient compliance with prescribed drug
      regimens utilizing electronic medication event monitors in RA, gout, and PMR
      showed that large differences exist in compliance between the various medication
      groups. Compliance declines over time. A regression model shows that it is
      possible to relate differences in patient compliance to a number of medication
      and patient related factors.

PMID- 12508390
TI  - Cyclic-AMP agonists inhibit antiphospholipid/beta2-glycoprotein I induced
      synthesis of human platelet thromboxane A2 in vitro.
AB  - OBJECTIVE: To investigate mechanisms responsible for increased thrombotic
      activity in systemic lupus erythematosus (SLE) associated with the
      antiphospholipid syndrome (APS). We had reported that anticardiolipin/beta2
      glycoprotein I (aCL/beta2-GPI) complexes induce platelet overactivity resulting
      in excessive production of thromboxane A2 (TXA2). Presumably this occurs by
      decreased platelet cyclic AMP (cAMP) activity and results in increased platelet
      aggregation. METHODS: We stimulated platelet intracellular cAMP generation with
      known cAMP agonists (dibutyryl cAMP, theophylline, and prostaglandin E1) and
      measured aCL/beta2-GPI induced platelet TXB2 production in vitro. Isolated human
      platelets were prelabeled with 14C-arachidonic acid and then challenged with
      aCL/beta2-GPI in the presence or absence of cAMP-activating substances. The
      resulting 14C labeled TXB2 was quantified by thin layer chromatography and
      radioactive scanning. RESULTS: We found a marked decrease in aCL/beta2-GPI
      induced platelet TXB2 production by the cAMP agonists in a dose dependent manner.
      CONCLUSION: Our findings suggest the usefulness of cAMP agonists in the control
      of thrombosis in some patients with SLE and APS.

PMID- 12508391
TI  - Nitric oxide synthase 2 promoter polymorphisms and systemic lupus erythematosus
      in african-americans.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease in which
      morbidity and mortality are higher in African-Americans. The etiology of this
      racial disparity is unknown. A genetic predisposition to enhanced nitric oxide
      (NO) production may predispose African-Americans to develop SLE and may increase
      disease severity. We have demonstrated a correlation between NO production and
      disease activity in SLE. Two polymorphisms in the inducible NO synthase (NOS2)
      promoter region (G-954C and CCTTT microsatellite repeat polymorphisms) are
      associated with improved outcome in some African patients with malaria. This
      study was designed to determine if these polymorphisms are associated with SLE.
      METHODS: We assessed the frequency of both the G-954C and CCTTT microsatellite
      repeat NOS2 promoter polymorphisms in a cohort of patients with SLE and age, sex,
      and race matched controls in North Carolina and South Carolina. RESULTS: Both
      polymorphisms were more frequent among African-American female SLE patients when
      compared with controls (p = 0.04 for the G-954C polymorphism and p = 0.03 for the
      CCTTT-8 repeat polymorphism). Further, the G-954C and CCTTT-8 repeat
      polymorphisms were in linkage disequilibrium (D cent = 0.89, p = 0.0001) among
      African-American female SLE patients. CONCLUSION: Altered genetic control of NOS2
      transcription may be a risk factor for SLE among African-American females. The
      extent of linkage disequilibrium between the G-954C and CCTTT-8 repeat NOS2
      promoter polymorphisms suggests that they were co-inherited.

PMID- 12508392
TI  - Correlation of serum collagen I carboxyterminal telopeptide concentrations with
      cutaneous and pulmonary involvement in systemic sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is characterized by fibrosis involving the
      skin and various internal organs. Type I collagen (Col I) is the most abundant
      extracellular matrix protein deposited in cutaneous involvement. We investigated
      Col I biochemical markers in patients with SSc. METHODS: All consecutive patients
      admitted for SSc over a 9 month period and a healthy control group were
      investigated. Serum concentrations of the C-terminal telopeptide of Col I (s-CTX
      I), C-terminal type I procollagen propeptide (PICP), osteocalcin, and bone
      alkaline phosphatases (ALP), and urinary concentrations of deoxypyridinoline (u
      DPD) and u-CTX-I were determined by ELISA. RESULTS: A total of 33 patients with
      SSc were included: mean age +/- SD was 54 +/- 12 yrs, with a mean disease
      duration of 5.4 +/- 3.9 years. Sixteen of 33 patients with SSc had s-CTX-I values
      exceeding the upper limit of normal values of the test and the mean +/- SEM was
      significantly higher (7388 +/- 1422 pmol/l) than in healthy controls (2800 +/-
      1120 pmol/l; p < 0.001). s-CTX-I correlated with the Rodnan skin score (p =
      0.003); it was higher in patients with diffuse disease (8459 +/- 3125; n = 14)
      than in patients with the limited form (6453 +/- 1235; n = 19; p < 0.02). This
      marker also correlated with acute phase reactants (C-reactive protein, p = 0.004;
      erythrocyte sedimentation rate, p = 0.02). s-CTX-I was high in patients with
      positive antitopoisomerase I autoantibodies (p = 0.04) and in patients with a
      decrease in forced vital capacity to less than 75% (p = 0.02). u-DPD
      concentration was high in patients with SSc (10.6 +/- 1.4 nmol/mmol creatinine vs
      6.3 +/- 2.1 in controls; p < 0.01). No difference between patients and controls
      or correlations with the disease were found for PICP, u-CTX-I, osteocalcin, and
      bone ALP concentrations. CONCLUSION: s-CTX-I, a marker of Col I degradation, is
      correlated with cutaneous and pulmonary involvement and with acute phase
      reactants in patients with SSc. This marker is a good candidate for further
      evaluation for disease activity and treatment purposes.

PMID- 12508393
TI  - Comprehensive study of autonomic function in a population with primary Sjogren's
      syndrome. No evidence of autonomic involvement.
AB  - OBJECTIVE: Autonomic neuropathy is associated with increased mortality. Autonomic
      nervous system disorders have been described in patients with primary Sjogren's
      syndrome (SS), but the results in controlled studies have been contradictory,
      varying from normal to sympathetic or parasympathetic dysfunction. Since the
      earlier studies employed varying methodologies, which may have led to the
      discrepancy, we conducted a comprehensive study on autonomic function in patients
      with primary SS and compared our findings to healthy, carefully matched
      population based controls. METHODS: A conventional cardiovascular reflex test
      battery (Valsalva maneuver, deep breathing test, active orthostatic test) and
      measurements of baroreflex sensitivity with phenylephrine and 24 hour heart rate
      variability were performed on 30 patients with primary SS and 30 healthy age and
      sex matched population based controls. RESULTS: There were no significant
      differences between the SS patients and the healthy controls in any of the tests.
      CONCLUSIONS: The prevalence of autonomic dysfunction is not increased in patients
      with primary SS compared to the general population.

PMID- 12508394
TI  - Baseline features and initial treatment as predictors of remission and relapse in
      Wegener's granulomatosis.
AB  - OBJECTIVE: To describe the course of disease activity and determine predictors of
      remission and relapse in a population based cohort of patients with Wegener's
      granulomatosis (WG). METHODS: Retrospective cohort study of 56 patients (median
      age 50 yrs) followed for 42.5 months. Disease activity was assessed by Birmingham
      Vasculitis Activity Score (BVAS-1) and permanent organ damage by Vasculitis
      Damage Index (VDI). Induction therapy consisted of prednisolone (Pred) 0.5-1
      mg/kg and cyclophosphamide (CYC) daily orally 2 mg/kg (19 patients) or
      intravenous pulses 15 mg/kg every 2nd week (32 patients). Baseline clinical and
      laboratory features and cumulative treatment during the first 6 months were
      recorded. Multiple Cox and logistic regression analyses were used to find risk
      factors for remission and relapse. RESULTS: All patients surviving > 1 month
      achieved either complete (85%) or partial remission (15%). Higher baseline BVAS-1
      increased the likelihood of achieving complete remission [BVAS-1 > 23, relative
      hazard (RH) 2.94, 95% confidence interval (CI) 1.48-5.85]. Relapse occurred in 31
      patients (60%) after a median period of 18 months. The risk of relapse was
      increased in patients having received < 10 g CYC during the first 6 months (RH
      2.83, 95% CI 1.33-6.02), in patients having received Pred > 20 mg/day for < 2.75
      months (RH 2.41, 95% CI 1.12-5.21), and in patients with initial heart
      involvement (RH 2.87, 95% CI 1.09-7.58). A higher Pred dose during the first 6
      months was associated with severe infections. Therapy resistance (no complete
      remission) was associated with baseline organ damage (VDI increase by 1, OR 1.53,
      95% CI 1.03-2.27). CONCLUSION: Initial high disease activity increased and the
      presence of baseline organ damage reduced the likelihood for complete remission
      in WG. Relapse was associated with less intensive initial treatment in terms of
      lower CYC doses and shorter time taking Pred > 20 mg/day.

PMID- 12508395
TI  - Structural characterization of a case-implicated contaminant, "Peak X," in
      commercial preparations of 5-hydroxytryptophan.
AB  - OBJECTIVE: To determine the chemical structure of a contaminant, X1, previously
      found in eosinophilia myalgia syndrome case-implicated 5-hydroxytryptophan (5
      OHTrp), and also present in over-the-counter (OTC) commercially available 5
      OHTrp. METHODS: Case-implicated 5-OHTrp as well as 6 OTC samples were subjected
      to accurate mass HPLC-mass spectrometry and HPLC-electrochemical detection, and
      reacted with reduced glutathione. Peak X1 was subsequently subjected to HPLC
      tandem mass spectrometry (MS/MS), as well as the resulting nucleophilic
      glutathione product. All these data were compared with analysis carried out under
      identical conditions on authentic 4,5-tryptophan-dione (Trp-4,5D). RESULTS: Based
      on accurate mass, tandem mass spectrometric analysis, and comparision with
      authentic standard compound analysis, X1 was determined to be 4,5-tryptophan
      dione, a putative neurotoxin. The presence of X1 in OTC samples varied from 0.5
      to 10.3% of the amount of Trp-4,5D present in case-implicated 5-OHTrp.
      CONCLUSION: Peak X1 was identified as the putative neurotoxin Trp-4,5D. It was
      found in case-implicated 5-OHTrp as well as 6 OTC samples. This gives some cause
      for concern in terms of the safety of such commercial preparations of 5-OHTrp.

PMID- 12508396
TI  - The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical
      characteristics and radiological outcome of psoriatic arthritis.
AB  - OBJECTIVE: To investigate the associations of the HLA-DRB1 rheumatoid arthritis
      shared epitope (SE) with clinical characteristics and radiological outcome in
      patients with psoriatic arthritis (PsA). METHODS: One hundred fifty-eight
      patients with well documented PsA and 250 controls were typed for HLA-DRB1
      alleles including the SE by polymerase chain reaction. Clinical data collected on
      the patient group included disease subset, swollen and tender joint counts, the
      psoriasis area severity index (PASI), and the presence of radiological erosions.
      Clinical and radiological associations with HLA-DRB1 and SE alleles were
      determined. RESULTS: There was an increased frequency of HLA-DR7 (41 vs 25%;
      puncorr = 0.001, OR 2.02, pcorr = 0.01) and a decreased frequency of HLA-DR2 (19
      vs 28%; puncorr = 0.03, OR 0.59, pcorr = 0.3) in the patient population compared
      with controls. There was no significant difference in the frequency of HLA-DR1
      and HLA-DR4 between patient and control populations. There was no significant
      difference in the prevalence of SE alleles between the patient and control
      populations (48 vs 54%). There was no increase in the prevalence of the SE in the
      polyarthritis subgroup, but there was a marginal decrease in those who remained
      in the oligoarthritis subgroup. There were no differences with respect to sex,
      age of onset of disease, family history, Health Assessment Questionnaire score,
      joint score, skin score, or nail score between those patients who were SE
      positive and those who were SE negative. However, significantly more patients who
      were SE positive developed radiological erosions (60 vs 43%; p = 0.03, OR 2.11).
      CONCLUSION: Overall, the prevalence of the SE in patients with PsA did not differ
      from our control population. However, it was overrepresented in those who
      developed radiological erosions. It is possible that the SE does have a role in
      the clinical severity of PsA.

PMID- 12508397
TI  - Lack of association of ankylosing spondylitis with the most common NOD2
      susceptibility alleles to Crohn's disease.
AB  - OBJECTIVE: To investigate whether the 3 most common mutations in the NOD2 gene
      that confer susceptibility to Crohn's disease (CD) are also associated with
      ankylosing spondylitis (AS). METHODS: DNA from 112 patients with AS and 168
      controls of homogenous Spanish ancestry were studied. The frequencies of the
      pathogenic alleles of NOD2 (3020insC, 2722G>C, and 2104C>T) were determined by
      analysis of the melting curves after hybridization with FRET probes on a Light
      Cycler real-time polymerase chain reaction (PCR) system. Results. NOD2 allelic
      frequencies in controls (3020insC, 0.009; 2722G>C, 0.009; 2104C>T, 0.042) did not
      significantly differ from patients with AS (3020insC, 0.009; 2722G>C, 0.004;
      2104C>T, 0.031). CONCLUSION: The 3 most common CD NOD2 mutations do not
      contribute to disease susceptibility to AS, and therefore do not explain the
      susceptibility locus for AS in chromosome 16q.

PMID- 12508398
TI  - Sporadic enteric reactive arthritis and undifferentiated spondyloarthropathy:
      evidence for involvement of Salmonella typhimurium.
AB  - OBJECTIVE: To define the candidate bacterial trigger and cytokine profile of
      synovial fluid mononuclear cells (SFMC) in patients with sporadic enteric
      reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA).
      METHODS: The study group comprised 10 patients with ReA and 23 with uSpA who
      fulfilled European Spondylarthropathy Study Group criteria. Ten patients with
      rheumatoid arthritis (RA) served as disease controls. IgG, IgA, and IgM
      antibodies to Shigella flexneri, Salmonella typhimurium, and Yersinia
      enterocolitica were measured in sera and SF by ELISA. Peripheral blood
      mononuclear cell (PBMC) and SFMC proliferation assays were done in the presence
      or absence of crude bacterial lysates. Bacterial antigens and DNA in synovial
      cells were detected by indirect immunofluorescence and polymerase chain reaction,
      respectively. Interferon-g (IFN-g), interleukin 10 (IL-10), and IL-4 were
      measured in 18 h SFMC culture supernatants in presence of bacterial lysate.
      RESULTS: Antibodies to S. typhimurium were significantly elevated in the sera of
      8 of 25 patients compared to controls (0/22; p < 0.05). The ratio of SF:serum
      anti-salmonella IgA was significantly higher in patients compared to controls (p
      < 0.0002). The ratio of SF:serum IgA antibodies to S. typhimurium was higher than
      that for S. flexneri (p < 0.007) and Y. enterocolitica (p < 0.05). Out of 25
      patients, 8, 2, and none had elevated antigen-specific SFMC proliferation
      response to S. typhimurium, S. flexneri, and Y. enterocolitica, respectively,
      whereas no control had elevated response. Salmonella antigens were detected in
      the synovial cells of 4 out of 14 patients. There was significantly higher IFN-g
      production from SFMC of patients who had increased proliferative response to
      Salmonella (LTT+) in the presence of Salmonella antigens compared to antigen
      control. The mean +/- SD of the ratio of IFN-g:IL-10 in the LTT+ patients was
      significantly lower compared to controls. Conclusion. S. typhimurium is probably
      one of the triggers for enteric ReA and uSpA in our cohort of patients, and the
      immune response is characterized by increased production of both IL-10 and IFN-g.

PMID- 12508399
TI  - Knee osteoarthritis compromises early mobility function: The Women's Health and
      Aging Study II.
AB  - OBJECTIVE: To examine associations between osteoarthritis (OA) of the knee and
      early functional limitations in a cohort of high-functioning older women, and
      evaluate the contributions of muscle strength, body weight, and pain severity to
      these limitations. Methods. Cross sectional analyses were conducted on baseline
      data of the Women's Health and Aging Study II (WHAS II), an observational study
      of disability transitions in a cohort of women aged 70-79 upon entry and who were
      representative of the one-third highest-functioning community-resident women.
      Standardized questionnaires and examinations were used to assess knee OA
      features, medication use, pain severity, knee extensor muscle strength, and body
      weight. Functional limitation was assessed using validated performance measures
      and self-report measures of task modification and task difficulty. RESULTS: Sixty
      nine women classified as "symptomatic" for knee OA, 48 with
      "asymptomatic/intermittently symptomatic," knee OA, and 285 with "no knee OA"
      were included in the final analysis. Despite selection for their high level of
      self-reported function, performance was slower and task modification was more
      frequently reported among women with knee OA than women without knee OA. Lower
      knee extensor strength, higher body weight, and greater pain severity were
      associated with knee OA, and also with functional limitations. Conclusion. Knee
      OA appeared to be associated with early functional limitations in this cohort of
      high-functioning, older, community-resident women. Lower knee extensor strength,
      higher body weight, and pain severity were closely associated with these
      limitations. The extent to which modification of these factors attenuates knee OA
      associated functional decline should be investigated.

PMID- 12508400
TI  - Association of heterozygous hemochromatosis C282Y gene mutation with hand
      osteoarthritis.
AB  - OBJECTIVE: To determine if there is an association between radiographic
      osteoarthritis (OA) of the hand and the presence of hemochromatosis HFE gene
      mutations. METHODS: One hundred seventy-six patients with radiographic OA of the
      hand were randomly selected from an academic rheumatology practice. We measured
      serum transferrin saturation (TS) and ferritin levels, and genotyped for the
      presence of the 2 common HFE mutations, C282Y and H63D. The prevalences of HFE
      mutations in these patients were compared to those in a hemochromatosis screening
      study from the same primary care patient base. RESULTS: There was a significantly
      increased prevalence of the C282Y mutation in the OA population compared to the
      unselected controls (12.5 vs 7.8%; p = 0.029). The prevalence of C282Y in OA was
      higher among older patients: 15.75% in the group older than 65 years versus 4.08%
      in the younger group. The mean TS level was higher among OA patients who were
      heterozygous for C282Y compared to those who lacked both HFE mutations (35.75 vs
      25.93%; p < 0.0001). This difference was also found in the general population.
      CONCLUSION: This is the first report to show an increased risk of OA among
      individuals who are heterozygous for the C282Y HFE mutation. The increase in this
      mutation in patients older than 65 suggests that this is associated with a late
      onset subset of OA. If this association is substantiated by larger randomized
      controlled studies, it could have major therapeutic implications in the
      development of specific therapy directed at individuals heterozygous for C282Y
      HFE mutation.

PMID- 12508401
TI  - Consistent low prevalence of arthritis in quebec: findings from a provincial
      variation study in Canada based on several canadian population health surveys.
AB  - OBJECTIVE: To examine interprovincial variations of arthritis prevalence focusing
      on comparisons between Quebec and the rest of Canada. METHODS: Data were derived
      from the 1991 General Social Survey (GSS), the 1991 Health and Activity
      Limitation Survey (HALS), and the 1994 and 1996 National Population Health
      Surveys (NPHS). Arthritis was variously ascertained through self-report of people
      aged 15 years or older. Prevalence in Quebec was compared with other provinces
      using extremal quotients (EQ) and correlation analysis. Multiple logistic
      regression analysis (1996 NPHS) was used to determine whether the low prevalence
      in Quebec persisted after controlling for confounding factors including age, sex,
      education, marital status, occupation, body mass index (BMI), comorbidity, and
      smoking. RESULTS: Quebec consistently had the lowest provincial prevalence of
      arthritis, with age-sex adjusted prevalences of 18.4% (GSS), 1.9% (HALS), 8.8%,
      and 10.1% (1994 and 1996 NPHS), which were significantly lower than the
      corresponding national estimates: 21.2%, 3.1%, 12.9%, and 13.3%. EQ from
      different surveys varied from 1.5 to 3.0 (significantly > 1). Correlation
      analyses reveal that relative rankings for provinces were consistent in all
      surveys. Logistic regression analyses showed a low risk of arthritis for
      Quebecois: odds ratio 0.75 (95% confidence interval 0.65, 0.87) after controlling
      for potential confounding factors. CONCLUSION: The low prevalence of arthritis
      observed in Quebec cannot be explained by potential confounding factors included
      in the NPHS and warrants further epidemiological studies.

PMID- 12508402
TI  - A cost effectiveness analysis of calcium and vitamin D supplementation,
      etidronate, and alendronate in the prevention of vertebral fractures in women
      treated with glucocorticoids.
AB  - OBJECTIVE: To assess the relative costs and benefits of calcium and vitamin D
      supplements, cyclic etidronate, or alendronate in the prevention of vertebral
      fractures for women and with normal bone density and osteopenia who are about to
      initiate moderate dose glucocorticoid treatment. METHODS: Using a decision
      analysis model, we evaluated the following patients: 4 hypothetical cohorts: 30
      yr-old women with normal lumbar spine (LS) bone mineral density (BMD) (t score =
      0), 50-yr-old women with borderline osteopenia (t score = -1), 60-yr-old women
      with moderate osteopenia (t score = -1.5), and 70-yr-old women with severe
      osteopenia (t score = -2) treated with a mean prednisone dose of 10 mg/day for
      one year. The main outcomes included the development of vertebral fractures 10
      years after glucocorticoid treatment and at age 80 (life-time risk) and direct
      and indirect costs. RESULTS: At 10 years, calcium and vitamin D supplements
      decreased fracture rates by 30-50% at a minimal cost (US$800 or less per
      vertebral fracture avoided) or at a cost saving compared to no treatment for
      women with osteopenia (t score -1 to -2). Etidronate and alendronate are most
      cost effective in women with borderline osteoporosis (t scores of -1.5 and -2) in
      the 10 year analysis. In the life-time analysis, calcium and vitamin D treatment
      yielded a cost savings compared to no treatment for all groups with osteopenia.
      Etidronate decreased fracture rates further in all groups at a cost of less than
      $2,000 per fracture prevented. Alendronate reduced the fracture risk further at
      cost of $3,000-7,000 per fracture avoided. CONCLUSION: Calcium and vitamin D
      supplements and low cost bisphosphonate regimens such as cyclic etidronate
      decrease the life-time vertebral fracture risk at acceptable costs and should be
      considered when initiating glucocorticoid treatment for women who do not have
      osteoporosis.

PMID- 12508403
TI  - Illness behavior and psychosocial factors in diffuse upper limb pain disorder: a
      case-control study.
AB  - OBJECTIVE: To compare behavioral and other psychosocial factors in patients with
      diffuse upper limb pain disorder (ULPD) and patients with carpal tunnel syndrome
      (CTS). METHODS: We compared 37 hospital outpatients with diffuse ULPD with 36
      hospital outpatients with CTS, matched by sex, pain intensity, and duration of
      illness. We assessed psychiatric morbidity by a standardized interview, and both
      symptoms and personality by self-rated questionnaires. We measured illness
      behavior by assessing financial benefits and compensation, coping strategies,
      illness beliefs, treatments received, and 24 hours of monitoring movements of the
      most affected arm and the body as a whole. RESULTS: There were no significant
      differences in the prevalence of either current or premorbid psychiatric
      disorders, personality scores, symptom amplification, disability, or treatments
      received. Subjects with ULPD had significantly lower self-rated scores for
      depression, somatic distress, sleep disturbance, and physical fatigue than
      subjects with CTS, although there were more than normal levels of anxiety,
      fatigue, and sleep disturbance in both groups. There were no significant
      differences in the numbers of arm or body movements by day and night.
      Significantly more ULPD subjects had been involved in litigation, but litigating
      patients were a minority. CONCLUSION: The primary etiology of endemic diffuse
      ULPD, presenting in secondary care, is no more psychiatric, psychological,
      behavioral, or related to personality than is the case with a similarly chronic
      and painful condition of known pathology. We cannot exclude either a specific
      role for psychosocial factors at work, or a more general role for psychosocial
      factors in maintaining disability in patients with chronic pain.

PMID- 12508404
TI  - Detection of interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha
      in skin of patients with fibromyalgia.
AB  - OBJECTIVE: To determine if abnormal collagen metabolism is correlated with
      neurogenic inflammation, a potential activator of collagen metabolism, in
      patients with fibromyalgia (FM). METHODS: The presence of inflammatory cytokines,
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-a was investigated
      in skin tissues by using reverse transcription-polymerase chain reaction (RT-PCR)
      and immunohistochemistry. Fifty-three skin biopsies from female patients with FM
      (30-65 years of age) were examined and compared to skin biopsies of 10 age and
      sex matched healthy controls. Biopsies were obtained from the left deltoid
      region. Rheumatoid arthritis synovial fibroblasts and tissues were used as
      positive controls for the expression of cytokines. Total RNA isolated from the
      tissue samples were reverse transcribed (RT) by random hexamers as the primer for
      RT followed by PCR amplification using specific primers for IL-1beta, IL-6 or TNF
      a. Expression of IL-1beta, and TNF-a protein was investigated in the skin by
      immunohistochemistry using specific antibodies (avidin-biotin method). RESULTS:
      Positive signals (RT-PCR) were detected in skin tissues of 19/50 (38%) FM
      patients for IL-1beta, in 14/51 FM patients (27%) for IL-6, and in 17/53 patients
      (32%) for TNF-a. None of the cytokines could be detected in healthy control skin.
      Immunoreactivity for IL-1beta and TNF-a was demonstrated in certain skin tissues
      of our FM patients. CONCLUSION: The detection of cytokines in FM skin indicates
      the presence of inflammatory foci (neurogenic inflammation) in the skin of
      certain patients (about 30% of FM patients), suggesting an inflammatory component
      in the induction of pain. This may explain the response to nonsteroidal
      antiinflammatory therapy in a subset of FM patients.

PMID- 12508405
TI  - Fibromyalgia, rheumatologists, and the medical literature: a shaky alliance.
AB  - A Medline literature review found that the total number of medical articles
      dealing with fibromyalgia (FM) has increased 5-fold during the past decade. The
      percentage of articles devoted to FM in rheumatology journals has increased
      modestly, from 1.3 to 2.6%. There is a wide variability of the number of articles
      on FM among these rheumatology journals. Recently, nonrheumatology journals have
      been publishing more articles on FM.

PMID- 12508406
TI  - A study of standard care in fibromyalgia syndrome: a favorable outcome.
AB  - OBJECTIVE: A longitudinal prospective study was undertaken to examine the outcome
      of fibromyalgia (FM) with standard medical care, as well as factors that might
      either predict or influence this outcome. METHODS: Eighty-two women with clinical
      FM were evaluated at baseline and 70 were followed for a mean of 40 months.
      Patients continued their usual management for FM as prescribed by their own
      physicians. The primary outcome variable was patient's overall status compared to
      baseline on a 7 point Likert scale (range 1 = much worse, 7 = much better).
      Secondary outcome measures included measurements for pain, fatigue, and patient
      and physician global assessment on a visual analog scale. Additional functional
      measures were the disease-specific Fibromyalgia Impact Questionnaire (FIQ), and
      the generic Health Assessment Questionnaire (HAQ). RESULTS: Of 70 (85%) patients
      who were followed up at 3 years, 33 (47%) reported overall moderate to marked
      improvement, and the remaining 53% reported either slight improvement, no change,
      or deterioration. The improved group (n = 33) compared to those that remained the
      same or worsened (n = 37) showed significant differences for change of score from
      baseline for tender point count, patient global assessment, sleep disturbance,
      fatigue, pain, FIQ and HAQ, and were younger, 46 versus 51 years. No other
      baseline demographic or disease variables discriminated between the 2 groups. The
      only baseline predictors for a favorable outcome were younger age and less sleep
      disturbance. CONCLUSION: The overall outcome in this group was favorable, with
      almost half the sample reporting clinically meaningful improvement in overall FM
      status. These findings are discussed in terms of their implications regarding
      current theory on the pathogenesis of FM.

PMID- 12508407
TI  - Health related quality of life among adults reporting arthritis: analysis of data
      from the Behavioral Risk Factor Surveillance System, US, 1996-99.
AB  - OBJECTIVE: To characterize health related quality of life (HRQOL) among people
      with and without self-reported arthritis in the general population by selected
      demographic and behavior characteristics. METHODS: We analyzed data from a cross
      sectional random-digit telephone survey [the Behavioral Risk Factor Surveillance
      System (BRFSS)] of civilian noninstitutionalized adults aged 18 years or older
      from 15 states and Puerto Rico, all of which used an optional arthritis survey
      module for one or more years from 1996 through 1999. We compared HRQOL among
      people with arthritis, defined as chronic joint symptoms (CJS) or doctor
      diagnosed arthritis, those within one of 3 arthritis subgroups (i.e., only doctor
      diagnosed arthritis, only CJS, and both doctor-diagnosed arthritis and CJS), and
      those without arthritis. RESULTS: On an age-adjusted basis, respondents with
      arthritis had significantly worse HRQOL than respondents without arthritis.
      Members of all 3 arthritis subgroups had significantly worse HRQOL than those
      without arthritis. Those with both CJS and doctor-diagnosed arthritis had
      consistently worse HRQOL than those with only CJS, who in turn had worse HRQOL
      than those with only doctor-diagnosed arthritis. In some of the demographic and
      behavioral subgroups, HRQOL differences between those with and without arthritis
      greatly exceeded the differences for the overall study. CONCLUSION: Because many
      adults report arthritis and because arthritis substantially worsens their HRQOL,
      HRQOL measures like those in the BRFSS may be useful in monitoring the burden of
      arthritis and in tracking the success of population interventions for arthritis.

PMID- 12508408
TI  - The Stanford Health Assessment Questionnaire: a review of its history, issues,
      progress, and documentation.
AB  - Over the last 2 decades, assessment of patient health status has undergone a
      dramatic paradigm shift, evolving from a predominant reliance on biochemical and
      physical measurements to an emphasis upon health outcomes based on the patient's
      personal appreciation of their illness. The Health Assessment Questionnaire
      (HAQ), published in 1980, was among the first instruments based on patient
      centered dimensions. The HAQ was designed to represent a model of patient
      oriented outcome assessment and has played a major role in diverse areas such as
      prediction of successful aging, inversion of the therapeutic pyramid in
      rheumatoid arthritis (RA), quantification of nonsteroidal antiinflammatory drug
      gastropathy, development of risk factor models for osteoarthrosis, and
      examination of mortality risks in RA. The HAQ has established itself as a
      valuable, effective, and sensitive tool for measurement of health status. It has
      increased the credibility and use of validated self-report measurement techniques
      as a quantifiable set of hard data endpoints and has contributed to a new
      appreciation of outcome assessment. We review the development, content, and
      dissemination of the HAQ and provide reference sources for its uses,
      translations, and validations. We discuss contemporary issues regarding outcome
      assessment instruments relative to the HAQ's identity and utility. These include:
      (1) the issue of labeling instruments as generic versus disease-specific; (2)
      floor and ceiling effects in scales such as "disability"; (3) distances between
      values on scales; and (4) the continuing introduction of new measurement
      instruments and their potential effects.

PMID- 12508409
TI  - Bone status evaluation with calcaneal ultrasound in children with chronic
      rheumatic diseases. A one year followup study.
AB  - OBJECTIVE: To evaluate at baseline and after one year the bone status in children
      with chronic rheumatic diseases (CRD) using quantitative ultrasound techniques.
      METHODS: We evaluated bone status in 67 children, 52 female, 15 male, age range
      2.80 to 18.10 years; 46 juvenile idiopathic arthritis, 11 juvenile
      dermatomyositis, and 10 systemic lupus erythematosus. Twenty-seven of 67 patients
      were taking only nonsteroidal antiinflammatory drugs (NSAID), 11 were given NSAID
      and methotrexate (MTX), 15 were also receiving steroids (prednisone), and 14
      patients were given steroids and alendronate. Broadband ultrasound attenuation
      (BUA) by bone was determined at the left calcaneus using two 12.5 mm diameter, 1
      MHz transducers mounted in hand-held calipers linked to a pediatric contact
      ultrasound bone analyzer. RESULTS: At baseline in the whole patient group mean
      BUA values and Z scores were significantly lower than in controls: 41.84 +/-
      21.64 vs 61.69 +/- 17.42 dB/MHz (p < 0.001); Z score -0.91 +/- 1.07 vs 0.09 +/-
      0.62 in controls (p < 0.001). At one year followup in the patient group BUA
      values were significantly increased compared to baseline (BUA 46.43 +/- 21.51
      dB/MHz; p = 0.002); no significant difference was found in Z score. The 15
      children receiving steroids in addition to NSAID and MTX showed a decrease in BUA
      value at one year (NS), while Z scores were significantly reduced compared to
      baseline (-1.45 +/- 1.40 vs -1.08 +/- 1.11; p < 0.05). The 14 patients in the
      group receiving NSAID and MTX who also received alendronate showed significant
      increases in BUA (56.93 +/- 19.32 vs 44.21 +/- 15.67; p < 0.001) and Z score (
      0.87 +/- 1.19 vs -1.56 +/- 0.82; p < 0.002). CONCLUSION: Contact ultrasound bone
      analysis at the calcaneus is a useful tool in the assessment and monitoring of
      bone status in children with CRD.

PMID- 12508410
TI  - Clinical and diagnostic value of genetic testing in 216 Israeli children with
      Familial Mediterranean fever.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disease
      with diverse clinical presentation. The FMF gene (MEFV) has recently been cloned
      and 30 point mutations causing the disease have been identified. We appraised the
      value of mutation analysis as a diagnostic test for FMF in symptomatic pediatric
      patients, and explored the possible correlations between MEFV genotypes and the
      diverse phenotypic expression of the disease. METHODS: Two hundred sixteen
      children who met the clinical criteria for FMF underwent molecular genetic
      studies to detect the 3 most common mutations in the Israeli FMF patient
      population (M694V, V726A, E148Q). The mutations found were related to clinical
      presentation and disease severity, using the Tel-Hashomer severity score.
      RESULTS: Of the 216 children who fulfilled the diagnostic criteria for FMF, 82
      (38.0%) had 2 of the tested mutations, 73 (33.8%) had only one mutation, and 61
      (28.2%) had none of the mutations studied. The M694V was the most frequent
      mutation, detected in 174 of 432 MEFV alleles (40.0%). The V726A mutation was
      found in 39 alleles (9.0%) and the E148Q mutation in 25 (5.8%). The severity
      score correlated with the number of mutations. Children with no mutations
      presented at an older age compared to children with one or 2 mutations. Children
      homozygous for the M694V mutation presented at a younger age, had a higher
      severity score, and more commonly had arthritis. CONCLUSION: Limited genetic
      molecular testing for MEFV mutations may explain some of the FMF clinical
      variability, but is diagnostically ineffective. The use of clinical criteria
      remains essential in establishing the diagnosis of FMF.

PMID- 12508411
TI  - Temporal artery bruits in a patient with giant cell arteritis.
AB  - Giant cell arteritis (GCA) is a disease of unknown etiology characterized by
      granulomatous inflammation of medium and large arteries. A 69-year-old man
      presented with right jaw claudication, intermittent scalp tenderness without
      headache, and visibly swollen temporal arteries. Results of a right temporal
      artery biopsy were positive for GCA. Auscultation revealed audible bruits of the
      temporal arteries. We believe this is the first reported example of bruits of the
      temporal arteries as a manifestation of GCA. The condition resolved with
      corticosteroid therapy.

PMID- 12508412
TI  - Linear scleroderma en coup de sabre and brain calcification: is there a
      pathogenic relationship?
AB  - Extracutaneous calcifications are rare in scleroderma and related conditions. We
      describe a female patient with linear scleroderma en coup de sabre and a
      longstanding clinical history of tonic and clonic convulsions. Radiographic study
      showed extensive cerebral calcifications in the right occipital hemisphere,
      homolateral to the involved side of her face. This report further suggests a
      relationship between localized scleroderma and neurological manifestations. Brain
      imaging studies should be routinely performed in scleroderma patients exhibiting
      neurological manifestations, especially seizure disorder.

PMID- 12508413
TI  - Ankle and hindfoot arthropathy in hereditary hemochromatosis.
AB  - Arthropathy is a leading clinical manifestation of hereditary hemochromatosis
      (HH), but involvement of the ankle and hindfoot joints is rare. We describe 3
      male patients who presented with symmetrical pain and swelling of the ankles.
      Radiographs and magnetic resonance imaging showed severe osteoarthritic
      degenerative changes with a radiological triad of joint space narrowing,
      subchondral sclerosis, and cyst formation. In all 3 cases a homozygous C282Y
      mutation in the HFE gene was detected and liver biopsies confirmed the diagnosis
      of HH. Other differential diagnoses could be excluded. Severe arthropathy of the
      ankle and hindfoot in comparatively young men can be a leading presentation of
      HH.

PMID- 12508414
TI  - A medical soft tissue mass of the knee.

PMID- 12508415
TI  - Not for sale, not even for rent: just say no. Thoughts about the American College
      of Rheumatology adopting a code of ethics.

PMID- 12508416
TI  - Do gastroprotective drugs prevent NSAID toxicity?

PMID- 12508417
TI  - Treatment resistant ankylosing spondylitis with peripheral joint involvement - a
      case for infliximab?

PMID- 12508418
TI  - Clinical and immunological factors associated with low lacrimal and salivary flow
      rate in patients with primary Sjogren's syndrome.

PMID- 12508419
TI  - Intrathecal corticosteroids for systemic lupus erythematosus with central nervous
      system involvement.

PMID- 12508420
TI  - Lupus-like syndrome and vasculitis induced by valpromide.

PMID- 12508421
TI  - [Hemodynamic changes of microvascular anastomosis with nitinol clips].
AB  - OBJECTIVE: To investigate the hemodynamic changes of the end-to-end anastomosed
      arteries with nitinol clips. METHODS: Fifteen New Zealand rabbits were divided
      into anastomosis clip group, suture group and control group randomly. The carotid
      arteries were resected and end-to-end anastomosis were carried out with nitinol
      clips in anastomosis clip group and with traditional suture in suture group. The
      carotid arteries remained undamaged in control group. On the days of 3, 9, 21 and
      30 postoperatively, mean blood velocity (Vm), pulsatility index (PI) and
      resistance index (RI) of anastomosed arteries were determined by Ultrasonography
      Doppler. RESULTS: On the days of 8 and 9 postoperatively, there were no
      significant differences of VM, PI and RI between two experimental groups (P >
      0.05). On the days of 20 and 30 postoperatively, the differences of Vm and RI
      were significant (Vm: P < 0.01, P < 0.05: RI: P < 0.01, P < 0.05). The
      hemodynamic restoration of the anastomosis clip group was better than that of the
      suture group. CONCLUSION: The hemodynamics of arteries anastomosed with nitinol
      clips is better than that with traditional suture. This technique has practical
      value clinically.

PMID- 12508422
TI  - [Scanning electronic microscope observation of elastic fiber of anastomosed
      artery].
AB  - OBJECTIVE: To observe the architecture of elastic fiber of anastomosed artery.
      METHODS: The right femoral arteries of 60 Wistar rats were cut off transversely
      and end-to-end anastomosis were performed. On the 3rd, 7th, 14th, 21st, 30th and
      90th days after operation, the anastomosed artery segments were harvested and
      fixed by 10% formalin. After routine processed, the architecture of elastic fiber
      of anastomosed artery was observed under scanning electronic microscope and was
      compared with that of normal artery. RESULTS: On the 3rd and 7th days after
      anastomosis, there was no the elastic fiber in the middle of the anastomosed
      area. From 14 to 90 days after anastomosis, the newborn elastic fiber connected
      the anastomosed area. The reconstruction of elastic fiber could be divided into
      quiescent stage, proliferation stage, and rebuilding stage. CONCLUSION: The
      reconstruction of elastic fiber occurs after arterious anastomosis and newborn
      elastic fiber originates from endoarterious layer. The structure of elastic fiber
      can return to normal 30 days after anastomosis.

PMID- 12508423
TI  - [Subfascial endoscopic perforator vein surgery in treatment of varicose of lower
      limb].
AB  - OBJECTIVE: To investigate the therapeutic effect of subfascial endoscopic
      perforator vein surgery (SEPS) in treatment of varicose of the lower limb.
      METHODS: From 1999. 11 to 2000. 12, 108 patients with varicose of the lower limb
      underwent venous surgery and 34 of them were treated by SEPS. There were 16 males
      and 18 females aged 20-79(averaged 51.4 years). Thirty limbs (26 cases) had open
      ulcers and the diameter of ulcer was 1.5-12.0 cm. Eleven limbs (8 cases) had
      severe pigmentation and the skin changes had been presented for 1 month to 15
      years. According to the severity of illness, flush saphenofemoral ligation, great
      saphenous vein stripping, percutaneous continuous venous circum suture, external
      femoral vein valve repair and SEPS were performed separately or simultaneously.
      RESULTS: Active ulcers healed in 19 limbs after 1 month, in 7 limbs after 3
      months, and in the other 4 ulcers after skin transplantation. There was no ulcer
      recurrence during follow-up (ranged 9-22 months). CONCLUSION: SEPS can accelerate
      the healing of venous ulcers, and it is one of important methods in the treatment
      of chronic venous insufficiency.

PMID- 12508424
TI  - [Revascularization of limb blood supply by arterialization of vein in extensive
      arterial oblitery ischemia].
AB  - OBJECTIVE: To investigate the effect of arterilization of veins in treatment of
      extensive arterial oblitery ischemia of limbs. METHODS: Eighteen lower limbs and
      six upper limbs with symptoms of chronic ischemia were diagnosed as having
      extensive occlusion of the major arteries by color-Doppler Ultrasonic Scanning
      and DSA. According to the level of occlusion, the involved limbs were treated by
      arterilization of veins in one-stage. RESULTS: During hospitalization, one lower
      limb was amputated. Seventeen lower limbs and six upper limbs were followed up
      for 3 to 26 months. Among them, one lower limb was amputated for necrosis of toes
      after 3 months; the outcomes of the others were satisfactory. By Doppler
      scanning, the arterial blood flow was observed after operation. CONCLUSION:
      Arterilization of veins in extensive arterial oblitery ischemia of limbs is a
      simple and effective treatment with good results.

PMID- 12508425
TI  - [Diagnosis and treatment of Klippel-Trenaunay syndrome].
AB  - OBJECTIVE: To investigate the diagnostic criteria and therapeutic method of the
      Klippel-Trenaunay syndrome. METHODS: Among 5 cases, there were 2 males and 3
      females aged from 11 days to 73 years. Vasography was carried out in all five
      patients and MRA was performed in one patients. RESULTS: After operation, the
      symptoms improved in 4 cases: the portine-like erythemas on their limbs got
      unclear; the focuses diminished obviously; the circumferences of the suffered
      limbs shrank and the ulcer healed. For following-up period was not long enough,
      the long term therapeatic result was still uncertain. CONCLUSION: Once the
      diagnosis of the Klippel-Trenaunay syndrome was made, operation should be
      performed as early as possible. If the surgical time is selected in prepuberty,
      optimal result can be expected.

PMID- 12508426
TI  - [Salvage of lower limb with long-time injury of popliteal artery].
AB  - OBJECTIVE: To evaluate the rate of salvage of lower limb with long-time injury of
      popliteal artery. METHODS: Twenty-one patients with injury of popliteal artery
      were treated. The interval between injury and repair of artery ranged from 12 hrs
      to 48 hrs. The essences of operation were thorough debridement of the ischemic
      and necrotic muscles, primary suture of wound, and repair of popliteal artery on
      the basis of reduction and fixation of fracture. RESULTS: The limb salvage were
      achieved in 19 cases. The saved limbs could fulfill the basic function of walk.
      CONCLUSION: Thorough debridement of ischemic and necrotic muscle and primary
      suture of wound were reasonable methods which could treat long-time injury of
      popliteal artery without amputation.

PMID- 12508427
TI  - [Effect of simvastatin on bone morphogenetic protein-2 expression and alkaline
      phosphatase activity of bone marrow stromal cell].
AB  - OBJECTIVE: To study the effect of simvastatin on the expression of bone
      morphogenetic protein-2 (BMP-2) and alkaline phosphates (ALP) activity in the
      primary cultured bone marrow stromal cells, and to elucidate the mechanism of the
      anabolic osteogenetic effect of simvastatin. METHODS: Bone marrow stromal cells
      in femur and tibia of adult mouse were cultured in vitro. after treated with
      different concentrations of simvastatin (0, 0.1, 0.2, 0.5 and 1.0 mumol/L) or
      recombinant human BMP-2 for 72 hours, ALP activity of bone marrow stromal cells
      was determined. BMP-2 expression of bone marrow stromal cells was analyzed by
      using immunocytochemistry and Western blotting. RESULTS: After treated with
      simvastatin for 72 hours, BMP-2 expression increased, while little BMP-2
      expression could be observed in the control group. ALP activity also increased in
      a dose-dependent manner; t-test showed that ALP activity in the group which
      concentrations of simvastatin were 0.5 mumol/L (t = 2.35, P = 0.041), 1.0 mumol/L
      (t = 2.348, P = 0.041) had significant difference when compared with control
      group. CONCLUSION: Simvastatin lead to high expression of BMP-2 in bone marrow
      stromal cells, via the increased auto- or para-crine of BMP-2, and ALP activity
      increased. These may be parts of the mechanism on the anabolic osteogenetic
      effect of simvastatin.

PMID- 12508428
TI  - [Treatment of traumatic soft tissue defect by vacuum sealing].
AB  - OBJECTIVE: To investigate the clinical effect of vacuum sealing in treatment of
      traumatic soft tissue defect. METHODS: From 1998. 8 to 2001. 2, 49 patients with
      55 traumatic soft tissue defects were treated by vacuum sealing after
      debridement. Among them, there were 39 males and 10 females with mean age 38. 4
      years. The wound area varied from 10 cm x 10 cm to 30 cm x 30 cm. In the
      experimental group, the wound surfaces or cavities were filled with polyvinyl
      alcohol foams with embedded drainage tubes connected with vacuum bottle (negative
      pressure of 50-60 kPa). Wound closure was performed with secondary suturing, or
      skin transplantation, or local flap grafting after 5-7 days. Besides, 126
      patients were managed by traditional dressing as the control group. RESULTS: Out
      of 51 traumatic soft tissue defects (45 patients), the wound closure was
      performed with a free flap in 4, with local flap in 8, with skin grafting in 27,
      with secondary suturing in 6, and with vacuum sealing directly in the other 6
      defects. Forty-five patients recovered and no complications (systemic and
      located) occurred. There were significant differences in time of secondary
      suturing, times of dressing, wound shrink and total therapeutic cost between two
      groups (P < 0.01). CONCLUSION: Vacuum sealing can protect the wound against
      contamination, evacuate the wound exudates completely, stimulate the growth of
      granulation tissue, and facilitate the wound healing; so vacuum sealing is a
      simple and effective method in treatment of traumatic soft tissue defect.

PMID- 12508429
TI  - [Instant repair of soft tissue defect of limb by simple skin traction technique].
AB  - OBJECTIVE: To summarize the application of simple skin traction technique in
      repair of soft tissue defect of limb. METHODS: From 1999, 42 cases of soft tissue
      defect of limbs were repaired by simple skin traction technique instantly; the
      defect area ranged from 2.5 cm x 2.0 cm to 8.0 cm x 6.5 cm. RESULTS: The soft
      tissue defect less than 8.0 cm can be sutured instantly. All of the wound
      achieved primary healing without infection and necrosis of skin edge, the
      circulation and sensation of limbs were normal; healing time was 10 days to 16
      days, 12.8 days on average. Thirty-two cases were followed up for 6 months; the
      shape and function recovered well. CONCLUSION: Simple skin traction technique is
      a good option to repair the soft tissue defect of limbs.

PMID- 12508430
TI  - [Repair of skin defect after resection of cutaneous malignant tumor].
AB  - OBJECTIVE: To investigate the clinical effects of repairing skin defect after
      resection of cutaneous malignant tumors. METHODS: From 1984 to 2001, cutaneous
      malignant tumors of 38 patients were resected and diagnosed pathologically. There
      were 12 cutaneous squamous cancer, 14 carinal cutaneous fibrosarcomas, 2 in situ
      cancers, 1 wart like cancer, 4 eczematoid cancers, and 5 deteriorative chronic
      ulcers. The biggest skin defect was 14 cm x 20 cm in size. Skin defects were
      repaired with flaps, myocutaneous flaps, free skin grafts and suturations. There
      were 4 gastronomies flaps, 6 latissimus flaps, 2 tensor fascia lata myocutaneous
      flaps, 1 transverse recuts abdominis myocutaneous flap, 5 plantaris medialis
      flaps, 3 random flaps, 12 free skin grafts and 5 suturings. RESULTS: All the
      operations succeed. Among 21 cases followed up for 3 to 12 years, 19 healed and 2
      relapsed, but the 2 patients healed after second operation. CONCLUSION: Thorough
      resection of tumor is the key to eradicate malignant tumor. The method to repair
      skin defect after resection should be chosen according to the patients
      individually.

PMID- 12508431
TI  - [Anatomical study on reverse flap of dorso-ulnar aspect of mid-hand and its
      clinical application].
AB  - OBJECTIVE: To provide anatomical bases for dorso-ulnar aspect of mid-hand reverse
      flap. METHODS: After red latex was infused into the arteries of 40 sides of adult
      cadava upper limbs, the origin, course, branches, distribution and distal
      anastomosis on the dorsal carpal branch of ulnar arteries were observed. And the
      mid-hand flap transfer was used to repair two cases of soft tissue defect (ranged
      4.5-5.0 cm x 2.0-3.5 cm on ring and little fingers). RESULTS: The dorsal carpal
      branch begins with ulnar artery (3.9 +/- 1.2) cm above the pisiform with diameter
      of (1.3 +/- 0.2) mm, and branches off into ascending and descending branches. The
      descending one is the continuing of dorsal branch, it crosses the ulnar edge of
      the fifth metecarpal bone and anastomizes with the digital artery of little
      finger or hypothenar branch of deep palmar (accounted for 70%). While the other
      ascending branch with the former two branches formed anastomosis accounts for
      30%. The two cases got healed in one-stage. The function of fingers recovered
      after 3-4 month follow-up. CONCLUSION: The reverse flap of dorso-ulnar aspect of
      mid-hand is available to repair the soft tissue defect on dorsum of hand with
      neighbor finger.

PMID- 12508432
TI  - [Treatment of refractory ulcers on sole of forefoot with reversed medial plantar
      flap].
AB  - OBJECTIVE: To provide a new reconstructive method to treat refractory ulcers on
      the sole of the forefoot. METHODS: The reversed medial plantar flap with the
      medial plantar pedal artery and vein as pedicle was used to treat the refractory
      ulcers on the sole of the forefoot in 5 cases. The size of the flap was 3.5-5.0
      cm x 4.0-5.5 cm. The deformities were corrected at the same time and the flaps
      were protected after operation. RESULTS: All flaps survived without
      complications. There was no recurrence after 6-month following-up. The patients
      could walk. CONCLUSION: The distal ends of medial plantar pedal artery and vein
      have plenty anastomoses with dorsal pedal artery and deep plantar arch. The
      reversed medial plantar flap has reliable blood supply by these anastomoses. The
      reversed medial plantar flap should be a choice in treating refractory ulcers on
      the sole of the forefoot.

PMID- 12508433
TI  - [Basic fibroblast growth factor inhibits promoter activities of human alpha 1(I)
      procollagen gene induced by transforming growth factor-beta 1].
AB  - OBJECTIVE: To investigate the effects of basic fibroblast growth factor (bFGF) on
      the promoter activities of human alpha 1(I) procollagen gene and the interaction
      between bFGF and transforming growth factor-beta 1 (TGF-beta 1). METHODS:
      Fibroblasts of the hypertrophic scar and normal skin from a 3-year-old patient
      were primarily cultured and subcultured in vitro. Both of the fibroblasts were
      transient transfected with phCOL 2.5, containing -2.5 kb of 5'f lank sequence of
      human alpha 1(I) procollagen gene and CAT reporter gene by FuGENE transfection
      reagent; and treated thereafter by 16 ng/ml bFGF, 2 ng/ml TGF-beta 1 and 16 ng/ml
      bFGF + 2 ng/ml TGF beta 1 for 24 hours. The relative CAT expression values were
      determined by CAT-ELISA. RESULTS: TGF-beta 1 strongly induced the CAT expression
      level, however, bFGF not only inhibited the basal CAT expression but also reduced
      the CAT expression up-regulated by TGF-beta 1 in normal skin and hypertrophic
      scar fibroblasts (P < 0.05). CONCLUSION: bFGF can reduce the promoter activities
      of human alpha 1(I) procollagen gene and antagonize the role of TGF-beta 1 in up
      regulating the promoter activities of human alpha 1(I) procollagen gene in normal
      skin and hyertrophic scar fibroblasts.

PMID- 12508434
TI  - [Overexpression of truncated type II transforming growth factor-beta receptor in
      dermal fibroblasts].
AB  - OBJECTIVE: To study the effect of overexpression of truncated type II TGF-beta
      receptor on transforming growth factor-beta 1(TGF-beta 1) autoproduction in
      normal dermal fibroblasts. METHODS: In vitro cultured dermal fibroblasts were
      treated with recombinant human TGF-beta 1(rhTGF-beta 1) (5 ng/ml) or recombinant
      adenovirus containing truncated type II TGF-beta receptor gene (50 pfu/cell).
      Their effects on regulating gene expression of TGF-beta 1 were observed with
      Northern blotting. RESULTS: rhTGF-beta 1 up-regulated the gene expression of TGF
      beta 1 and type I procollagen. Overexpression of truncated receptor II down
      regulated the gene expression of TGF-beta 1. CONCLUSION: Overexpression of the
      truncated TGF-beta receptor II decreases TGF-beta 1 autoproduction via blocking
      TGF-beta receptor signal. The results may provided a new strategy for scar gene
      therapy.

PMID- 12508435
TI  - [Effect of Salvia miltiorrhiza on autocrining growth factor by fibroblasts
      cultured in vitro].
AB  - OBJECTIVE: To investigate the mechanism of overhealing alleviation by salvia
      miltiorrhiza (SM) in wound healing. METHODS: Fibroblasts were cultured in vitro,
      and SM was applied with different concentrations (40, 80, 160 and 320
      micrograms/ml) and time(the 1st, 2nd, 3rd, 4th and 5th days) to influence their
      autocrine. The levels of transforming growth factor-beta 1 (TGF-beta 1) and
      epidermal growth factor (EGF) were determined by ELIAS and radioimmunoassay
      respectively. RESULTS: The SM could inhibit autocrine of TGF-beta 1 by
      fibroblasts (P < 0.05). However, it did not affect autocrine of EGF (P > 0.05).
      CONCLUSION: The above results indicate that SM reduces overhealing by inhibiting
      the autocrine of TGF-beta 1 selectively.

PMID- 12508436
TI  - [Experimental study on injury of dorsal root ganglia in lumbar radiculopathy].
AB  - OBJECTIVE: To investigate the effects of nerve root compression on dorsal root
      ganglia. METHODS: Following the method of Kawakami, 4/0 ribbon gut were applied
      around left L4-6 spinal nerve roots in 50 SD rats. Just 3 mm cranial to the
      dorsal root ganglia, the nerve roots were secured by two ligation node. The nerve
      roots of right side were as control. The L4-6 spinal cord was taken out 1, 2, 4,
      8, 12 weeks after surgery, respectively. The activity of fluoride resistant acid
      phosphatase (FRAP) was determined by the enzyme histochemistry (Gomori method)
      and the image analysis technique. RESULTS: In the test side, the FRAP content of
      spinal dorsal horn reduced 4 weeks after operation. And there were gradually more
      and more decreases from 4 to 12 weeks. There was significant difference between
      the test side and control side (P < 0.01). CONCLUSION: Chronic nerve root
      compression causes damage to dorsal root ganglia.

PMID- 12508437
TI  - [Preliminary result of allogenic bone and autogeneic-iliac bone in comminuted
      fracture reparation in rabbits].
AB  - OBJECTIVE: To observe the difference of the fracture reparation using autogeneic
      iliac bone and allogenic bone. METHODS: Comminuted fracture of humerus in two
      sides were made in rabbits. Autogeneic-iliac bone was implanted in one side,
      while allogenic bone of equal capacity was implanted in the other side. General
      observation, X-ray, and HE histologic section were done when the rabbits were put
      to death in different stages. RESULTS: One week after implantation, the graft had
      been enclosed by connective tissue without infiltration of the inflammatory
      cells. At the 2nd week, the graft had been enclosed in osteoplastic granulation
      tissue, and the cartilage callus had formed. At the 3rd week, there had been
      broken sequestrum among the callus; the cartilage had actively formed the bone;
      and the medulla had been making. At the 4th week, the sequestrum had disappeared,
      and the mature callus had appeared; the osteoblasts had arranged in a line around
      the edge of the mature callus. At the 5th week, the callus was strong, compact
      and approached mature bones. At the 6th week, there had been the compact lamellar
      structures and the complete haversian's systems. There was no significant
      difference between callus of two sides by using image quantitative analysis in
      the 3rd, 4th week (P > 0.05). CONCLUSION: The allogenic bone has good
      histocompatibility and bone conduction effect, and can be used for bone
      transplantation substitute with autogenous-iliac bone.

PMID- 12508438
TI  - [Diagnosis and treatment of tarsal tunnel syndrome in 10 cases].
AB  - OBJECTIVE: To discuss the diagnosis and treatment of tarsal tunnel syndrome.
      METHODS: From 1998 to 1999, 10 cases of tarsal tunnel syndrome were reviewed, and
      the outcomes of operation were analyzed according to Pefeiffer's method. Out of
      10 cases, 6 were examined using electromyography preoperatively. RESULTS: After 1
      to 2 year follow-up, postoperative outcomes were excellent in 5 cases, good in 4
      cases, and poor in 1 case according Pefiffer's methods. CONCLUSION: A combination
      of symptoms and physical signs, and electromyography may increase the diagnosis
      rate; and early operation will improve the therapy results.

PMID- 12508439
TI  - [Surgical reconstruction of velopharyngeal incompetence in postoperative cleft
      palate patients].
AB  - OBJECTIVE: To explore the clinical result of velopharyngeal cerclage in repairing
      velopharyngeal incompetence of postoperative cleft palate patients. METHODS: From
      1987 to 2000, 25 cases of velopharyngeal incompetence due to postoperative cleft
      palate were given the velopharyngeal cerclage. The mucosa flap of palate was
      pushed back, the autogenous free grafts of denervated skeletal muscle were
      selectively used for velopharyngeal cerclage. All the patients were followed up
      for 2 and a half years on average. RESULTS: All the patients achieved good
      results with velopharyngeal competence and good articulation. The patients' sound
      of voices was clear. CONCLUSION: This method can be used to repair velopharyngeal
      incompetence of postoperative cleft palate patients; the operation is simple and
      the results are satisfactory.

PMID- 12508440
TI  - [Effects of bone morphogenetic protein on proliferation and collagen-1 synthesis
      of skeletal muscle satellite cells].
AB  - OBJECTIVE: To investigate the effects of bone morphogenetic protein (BMP) on the
      proliferation and collagen synthesis of skeletal muscle satellite cells. METHODS:
      Skeletal muscle satellite cells were harvested and cultured in vitro. The 0
      ng/ml, 50 ng/ml, 100 ng/ml, 500 ng/ml, and 1000 ng/ml BMP were used to induce
      skeletal muscle satellite cells for 48 hours. Cell proliferation, rate of myotube
      formation and collagen-1 synthesis were measured. RESULTS: BMP promoted cell
      proliferation and reduced the rate of myotube formation. Collagen synthesis
      increased when skeletal muscle satellite cells were induced with more than 500
      ng/ml BMP. And the higher the concentration of BMP was, the stronger this effect
      became. CONCLUSION: BMP can enhance the proliferation of skeletal muscle
      satellite cells and change their differentiation from myoblasts to osteoblasts.

PMID- 12508441
TI  - [Feasibility of calcium polyphosphate fiber as scaffold materials for tendon
      tissue engineering in vitro].
AB  - OBJECTIVE: To study the feasibility of calcium polyphosphate fiber (CPPF) as the
      scaffold material of tendon tissue engineering. METHODS: CPPF (15 microns in
      diameter) were woven to form pigtail of 3 mm x 2 mm transverse area; and the
      tensile strength, porous ratio and permeability ratio were evaluated in vitro.
      Tendon cells (5 x 10(4)/ml) derived from phalangeal flexor tendon of SD rats were
      co-culture with CPPF scaffold or CPPF scaffold resurfaced with collagen type-I
      within 1 week. The co-cultured specimens were examined under optical and electric
      scanning microscope. RESULTS: The tensile strength of CPPF scaffolds was (122.80
      +/- 17.34) N; permeability ratio was 61.56% +/- 14.57%; and porous ratio was
      50.29% +/- 8.16%. CPPF had no obvious adhesive interaction with tendon cells,
      while CPPF of surface modified with collagen type-I showed good adhesive
      interaction with tendon cells. CONCLUSION: The above results show that CPPF has
      some good physical characteristics as scaffold of tendon tissue engineering, but
      its surface should be modified with organic substance or even bioactive factors.

PMID- 12508442
TI  - [Comparative study on graft of autogeneic iliac bone and tissue engineered bone].
AB  - OBJECTIVE: To compare the clinical results of repairing bone defect of limbs with
      tissue engineering technique and with autogeneic iliac bone graft. METHODS: From
      July 1999 to September 2001, 52 cases of bone fracture were randomly divided into
      two groups (group A and B). Open reduction and internal fixation were performed
      in all cases as routine operation technique. Autogeneic iliac bone was implanted
      in group A, while tissue engineered bone was implanted in group B. Routine
      postoperative treatment in orthopedic surgery was taken. The operation time,
      bleeding volume, wound healing and drainage volume were compared. The bone union
      was observed by the X-ray 1, 2, 3, and 5 months after operation. RESULTS: The
      sex, age and disease type had no obvious difference between groups A and B. all
      the wounds healed with first intention. The swelling degree of wound and drainage
      volume had no obvious difference. The operation time in group A was longer than
      that in group B (25 minutes on average) and bleeding volume in group A was larger
      than that in group B (150 ml on average). Bone union completed within 3 to 7
      months in both groups. But there were 2 cases of delayed union in group A and 1
      case in group B. CONCLUSION: Repair of bone defect with tissue engineered bone
      has as good clinical results as that with autogeneic iliac bone graft. In aspect
      of operation time and bleeding volume, tissue engineered bone graft is superior
      to autogeneic iliac bone.

PMID- 12508443
TI  - [Experimental study on kidney anatomic structure of banna minipig inbred-lines
      for xenotransplantation].
AB  - OBJECTIVE: To explore the kidney anatomic structure of banna minipig inbred
      lines, and to provide data for kidney xenotransplantation. METHODS: The fresh and
      infused kidneys of banna minipig (including the vessel and the ureter) were
      checked by anatomic microscope and vernier caliper in original location and away
      body. The tissue structure was observed by HE stain. RESULTS: The structure of
      kidney of banna minipig inbred-lines (including the vessel and the ureter) are
      similar to that of human being. The fascia propria of kidney is divided into
      three layers including capsula fibrosa, capsula adipose and fascia renalis. The
      thickness of cortex renalis is (20.0 +/- 2.4) mm. The average diameter of renal
      artery is 5.1 mm and is similar to that of human being. All the kidneys of banna
      minipig inbred-lines have a single branch renal artery. The diameters of left and
      right ureters are 5.1 mm and 4.7 mm, respectively. CONCLUSION: The kidney of
      banna minipig inbred-lines is an ideal replacement of human kidney for
      xenotransplantation.

PMID- 12508444
TI  - [Medical application of nano-materials].
AB  - OBJECTIVE: To review the research progress and medical application of nano
      materials. METHODS: The literature review and comprehensive analysis, methods
      were used in this study. RESULTS: The Nanotechnology is a typical crossing
      knowledge. It could be extensively applied in the fields of novel biomaterials,
      effective transmission of bioactive factor; the detection of functions for all
      vital organ systems, vascular circulation condition, the control of repair of
      burn trauma wounds will be monitored by the varied methods of nano technology
      combined with molecular biological engineering. CONCLUSION: The application of
      Nanotechnology will play important roles in clinical medicine, wound repair and
      basic research for the traditional Chinese medicine.

PMID- 12508446
TI  - [Cost-of-illness study of pneumococcal disease in Italian children].
AB  - Streptococcus pneumoniae (S pneumoniae, or pneumococcus) is a leading cause of
      illness in children, and causes illness and death among the elderly and persons
      with certain underlying conditions. A Cost-of-Illness (COI) estimate for each
      pneumococcal disease (meningitis, bacteremia, pneumonia, and otitis media) was
      determined using decision tree analysis that considered both direct and indirect
      costs. Information on the burden of pneumococcal disease in Italy, in terms of
      data on the incidence and seroprevalence of disease was collected from published
      and unpublished records, supplemented, and verified by Italian pediatric and
      infectious disease experts. The annual cost to society of caring for children
      with pneumococcal disease is estimated to be around 59,604,477 euro including
      both direct costs and indirect costs (productivity changes). Direct costs
      accounted for 39.9% of the total costs. The value of resources used to treat
      otitis media was 60.6% of the total direct costs; 31.9% was the value of
      resources for treating pneumonia; 6.5% for treating bacteremia; 1.0% for treating
      meningitis. A sensitivity analysis confirmed the robustness of the results.

PMID- 12508445
TI  - [Antibiotic microbial resistance surveillance in invasive infections caused by
      Streptococcus pneumoniae and Staphylococcus aureus: the EARSS (European
      Antimicrobial Resistance Surveillance System) project in Italy (April 1999-April
      2000)].
AB  - This paper presents the results of an Italian multicentric study conducted in the
      period April 1999-April 2000 in 64 clinical microbiology laboratories, aimed at
      collecting antimicrobial resistance data using a standard European protocol
      (EARSS Project, European Antimicrobial Surveillance System). A total of 1701
      strains of Staphylococcus aureus were isolated from blood and 367 strains of
      Streptococcus pneumoniae were isolated from blood (72.7%) or from CSF (27.3%).
      Methicillin resistance in S. aureus was found to be 42.1%; it was significantly
      higher in adults (RR = 6.6, CI 95% 2.5-17.0), in hospitals of Centre and North of
      Italy (respectively RR = 1.45, CI 95% 1.1-2.0; RR = 1.6, CI 95% 1.1-2.2), and in
      intensive care and surgery units (respectively RR = 1.8, IC 95% 1.6-2.0 and RR =
      1.7, CI 95% 1.4-1.9). Penicillin resistance in S. pneumoniae was found to be
      12.1%; it was higher in South Italy (RR = 3.5, CI 95% 1.9-6.6, in meningitis
      compared to sepsis (RR = 2.5, CI 95% 1.4-2.5) and in intensive care units
      compared to other departments (RR = 2.2, CI 95% 1.0-4.8). The level of
      erythromycin resistance in S. pneumoniae was of 28.2%, reaching 56.4% in
      penicillin resistant strains. These results suggest that a continued surveillance
      and effective control measures are required.

PMID- 12508447
TI  - [Active surveillance of nosocomial infections in heart surgery patients:
      implementation of the American National Nosocomial Infections Surveillance (NNIS)
      System in a large hospital in Rome].
AB  - The authors present the implementation of the American NNIS System method for
      active surveillance in the heart surgery and its intensive care unit (ICU) of a
      large hospital in Rome (almost 1.000 beds). This surveillance was based on full
      time infection control professionals. Device-associated infection rates were
      calculated for adult ICU surveillance component. For surgical patient
      surveillance component we used the surgical site infection (SSI) risk index based
      on wound class, duration of operation and American Society of Anesthesiology
      score. The NNIS System method allowed us to understand the most relevant problems
      in heart surgery patients: in comparison with NNIS data, we found high rates of
      SSIs both in procedures on valves and in coronary artery bypass grafts. The
      central line-associated bloodstream infection rate was higher than the American
      median rate. Therefore, we decided to focus on surgical risk factors linked to
      SSIs and to revise recommendations for intravascular-device use. In conclusion,
      in our experience the NNIS System method proved to be a very useful and versatile
      tool for nosocomial infections active surveillance.

PMID- 12508448
TI  - [Evaluation of the appropriateness of hospital use: the case of IRCCS Ospedale
      Maggiore di Milano, Italy].
AB  - In 1999 an Italian version of the AEP was applied to some units of the IRCCS
      Ospedale Maggiore di Milano and a modified AEP version was used to evaluate the
      day hospital activity. The main aims of the study were: to establish the
      appropriateness of the utilisation of beds and of day hospital activity and to
      calculate the costing of the misuse of hospital resources. 267 admission days
      were evaluated and 31.5% were not appropriated; whereas of 3,248 days of stay 37%
      were found not appropriated. The day hospital activity was evaluated through 300
      record referred to 570 days of treatment and 13% of them were not appropriated.
      The cost of the 1,201 not appropriated hospital days was over 351.000. The not
      appropriated level of hospital utilisation in the IRCCS Ospedale Maggiore di
      Milano is similar to what is reported in national and international literature.
      Our study highlights some limits in the application of the AEP protocol at high
      specialised hospital units.

PMID- 12508449
TI  - [The evaluation of efficacy and efficiency in the health care sector: separate or
      integrated moments?].
AB  - Studies on efficacy (clinical trials) and efficiency (Cost Benefit) in health
      care are frequently disjoint and carried on by researchers with different
      background in distinct moments. The origin of this division can be found in the
      profound conviction existing in the healthcare researchers that efficiency and
      efficacy are distinct and distant concepts, the former pertaining to the
      economist, the latter to the clinician. Many are the factors at the basis of this
      separation which consequently lead to the divergence between the two sector of
      analysis; among those, probably the most relevant factor is the distinction, in
      the healthcare sector, between the consumer (the patient) and the purchaser
      (private and/or public insurance). In reality, the organizational evolution of
      the health care systems, the consciousness of the interdependency between health
      and economic benefits, and the progressive shortage of economic resources for the
      growing healthcare needs, require a major integration of analyses concerning
      efficacy and efficiency. On this line of thought is moving the operational
      research where models such as the Data Envelope Analysis and the Semi-Markov
      Decisional Models have been developed.

PMID- 12508450
TI  - [Efficacy and critical implications of food handlers' professional training:
      analysis of an experience].
AB  - Our study aimed at both assessing the efficacy of the same training course in
      different contexts and training course repeated in the same context. We examined
      the most critical aspects, on which to develop further aimed course. In 1998 the
      Laboratory of Environmental Microbiology of the Institute of Hygiene (UCSC) has
      implemented 2 professional training courses both for food handlers of a refectory
      (course A) and of a hospital canteen (course B). Two years after a following
      course (C) in the hospital canteen. At the beginning and at the end of every
      course a questionnaire of 25 questions has been gathered in five areas. The data
      drawn by the questionnaires have been compared using the percentage of exact
      answers before and after the course. Correct answers beginning and end course: A
      89% and 94%, B 68% and 77%, C 76% and 78%. The correct answers beginning course C
      and end course B are not significatively different (p = 0.1963). Critical areas
      of the C and B courses have been "microbiological risks" and "correct
      temperatures"; at the end of the training both the areas had sensitive
      improvements (C 40% to 59%, 60% to 78%-B 31% to 69%, 45% to 78%). CONCLUSION:
      Food handlers professional training have been effective both in the same context
      and in a different context; the training should be based on both the operator's
      knowledge and difficulties met during the training; knowledge obtained by
      training is kept unchanged for some years, and it is supposed to repeat the
      course after one or two years; the analysis of the areas has confirmed the
      existence of critical problems, common causes of epidemics in collective catering
      services.

PMID- 12508451
TI  - [The problem of the aged person living alone: a methodological proposal for a
      pilot project of the aged person's and university student's cohabitation].
AB  - The objective of the present study was to evaluate the outcome of a promotion
      program for the cohabitation between healthy living-alone-old person and
      university student. The study aimed to highlight the benefits of both the parts
      in terms of psyco-physical behaviour of the old subject and of logistic and
      financial support for the student. The survey was carried out between 1998 and
      2000 on voluntary couples of old person-university student living in Padua. The
      study quantified the level of satisfaction of the material needs of the both
      parts and it also showed the affective relationship established between the old
      people and the young subjects.

PMID- 12508452
TI  - Tobacco consumption and sports participation: a survey among university students
      in northern Italy.
AB  - Social-demographic information of a total of 1249 students attending the
      University of Bologna was analyzed by means of an anonymous questionnaire
      containing 33 questions with particular reference to tobacco smoking and sports
      activity. Results revealed that 31.6% of the students practise some form of
      sports regularly (6 hours a week or more), 40.5% occasionally (at least an hour a
      week for 8 months in a year) and 27.9% do not take part in any kind of sport.
      Significant differences were seen between those that practise sports (60.4% are
      non-smokers and 33.5% are habitual smokers) and those that do not (52.9% are non
      smokers and 40.1% smoke habitually). The smokers who are active in sports smoke a
      lower mean number of cigarettes a day than the inactive group and thus belong to
      the category of light smokers. They also smoke fewer cigarettes on days when they
      take part in sports activity. As far as knowledge of health risks is concerned,
      21.1% of those who practise sports obtained a score between good and excellent
      compared to 15.9% of those who do not. Although on the whole the results appear
      to show a certain influence of sports on smoking habits, the kind of study we led
      and the differences in the number of smokers are not sufficient to consider
      sports practitioners as a group not at risk for behaviour harmful to the health.
      Further studies are necessary to verify the cause-effect relationship between
      sports activity and smoking habits.

PMID- 12508453
TI  - [Unusual sources of L. pneumophila in hospital environment].
AB  - Owing to the very frequent reports of Legionella's cases arising in italian
      hospitals we have done a microbiologic monitoring on some equipments utilized in
      a several ward, what represent a potential source of diffusion of germ. It has
      been analysed water collected from 135 bubblers for oxygen-therapy, 11 pediatric
      incubators and 10 dental chairs. The isolated strains ware 31 (19.23%), of which:
      3 L. Pneumophila sgr. 1; 11 sgr. 3; 8 sgr. 6; 2 sgr. 7. For 6 strains identified
      as Legionella, have not been possible to establish sgr.

PMID- 12508454
TI  - [The century of work].
AB  - The new Series of papers on Occupational Hygiene, now that the hygienists have
      been qualified also as "competent physicians", intends to make a comparison
      between the present and the past conditions of the human work. The present work
      is characterized by high specialization, more sophisticated technologies and
      continuous evolution, although in Italy we have consider a drop of the general
      occupational rate. According to such a situation, Italy must make alliance with
      the other countries, because, due to the globalization, the occupational problem
      has overcome the domestic borders.

PMID- 12508455
TI  - [Clinical and urologic management].
AB  - The concept of clinical management try to incorporate to the physicians the
      importance of their decessions regarding the dinamical and complex process of
      efficiency and health expenses. In this article the authors carry out a reflexive
      analysis of the reliable repercussion of this process into the healthy people,
      governmental authorities and assistencial setting of patients. It establish the
      involvement of the doctor in management, clinical management and it concludes the
      regulatory function to achieve the true clinical efficiency which harmonizes the
      relationship between the assistencial process and the corresponding resources
      consumption.

PMID- 12508456
TI  - [Uropediatrics. Update and controversies].
AB  - On the occasion of the 25 Anniversary of the official Journal of the Spanish
      Urological Association, we do an overall view of Spanish Pediatric Urology (U.P.)
      at present time, and we perform an updating of the most prevalent and
      controversial aspects in U.P., as the foetal Urology, the vesicoureteral reflux
      and the pyelo-ureteral stenosis.

PMID- 12508457
TI  - [Urethral surgery].
AB  - A propos of the 25 anniversairy of Actas Urologicas Espanolas it carry out a
      comprehensive up to date of the extended urethral surgery. The wide personal
      experience of the author rules through this revision ranging over the whole field
      of congenital abnormalities as well as the inherent complexity of surgical
      procedures and technical selection of for urethroplasty.

PMID- 12508458
TI  - [Extracorporeal shock-wave lithotripsy. An established treatment].
AB  - Extracorporeal shock wave lithotripsy (ESWL) is the most required urinary stone
      therapy in our country and in the rest of the world. In a way it has replaced the
      alternative treatments (open surgery, percutaneous nephrolithectomy,
      ureteroscopy). Nevertheless these therapeutic approaches have still its own
      indications. Although there is no a definitive agreement, it should be desirable
      a world-wide consensus where each therapy will have a exactly defined land with
      all potential of each management improved. We review ESWL technical aspects, its
      literature-based most accepted indications, adverse bioeffects and last, future
      improvements are considered.

PMID- 12508459
TI  - [Ultrasonography in urology].
AB  - After its introduction more than twenty years ago, ultrasound has continually
      increased in importance in urology diagnostics and is currently one of the most
      frequent exploratory techniques used. It corresponds to one out of every four
      imaging techniques carried out in medicine. The possibility of intervention under
      echographic control, for either diagnostic or therapeutic purposes, has been
      studied ever since ultrasound first appeared. Nowadays, interventionist
      echography is a commonly used technique in urology and is applied in a wide range
      of procedures carried out on the prostate gland, bladder and kidney that require
      echography-guided puncture techniques. Timely modifications of ultrasound for
      control and monitoring of treatments such as shock wave extracorporeal
      lithotripsy or transperineal brachitherapy has increased even more its day-to-day
      use by urologists. New technologies currently under development such as high
      energy ultrasound in the management of kidney and prostate cancer, 3-dimensional
      ultrasound, Doppler-energy and contrast ultrasound have also increased the
      importance of this procedure in urology.

PMID- 12508460
TI  - [Erectile dysfunction].
AB  - In Spain, based on the IIEF, 19% of males between 25 and 70 years old present
      some degree of erectile dysfunction (ED). Therefore, around 2,000,000 Spanish men
      present this condition and could require medical attention for it. Here, we
      present an up-date of the most important aspects of erectile dysfunction
      (pathophysiology, diagnosis and treatment). We review, in detail, the oral
      treatments and future drugs that are presently in the premarketing experimental
      phase. Diagnostic and therapeutic management of the patient with erectile
      dysfunction should be individualized, taking into account the goals of each
      patient. It is highly recommendable to carry out a basic assessment
      (comprehensive clinical history, physical examination, recommended lab testing).
      If previously undiagnosed diseases are discovered (diabetes, arteriosclerosis,
      etc.) these should be treated and modifiable risk factors should be corrected.
      There are numerous therapeutic options for the treatment of erectile dysfunction.
      Replacement therapy with testosterone should only be used in males with ED and
      low levels of this hormone, under medical supervision. At present, first line
      treatment consists of the administration of oral drugs (sildenafil, apomorphine).
      There are two new PDE 5 inhibitors (tadalafil and vardenafil) that will be
      released on the market 2003, which will provide better selectivity. Moreover,
      several drugs for oral administration are in the initial phases of research that
      will facilitate erection via a direct penile action. When oral drugs are
      contraindicated, are not effective or when they are unpopular with the patient,
      the second line of treatment is intracavernous injection. Prostaglandin E1 is the
      initial drug of choice in patients using intracavernous autoinjection for the
      first time and has a high efficacy. Implantation of a penis prosthesis and penile
      revascularisation are appropriate for highly selected patients. Psychotherapy can
      be an option for men with ED of psychogenic origin, either as a monotherapy or
      combined with sildenafil or apomorphine.

PMID- 12508461
TI  - [Mesenteric cyst with ureteral involvement].
AB  - We expose a mesenteric cyst with obstruction on the left ureter. Physical
      abdominal examination was essential in the mass diagnosis. Definitive location,
      size and liquid structure was confirmed by CT.

PMID- 12508462
TI  - [Typical renal metanephric adenoma. Conservative surgery].
AB  - Metanephric Adenoma is uncommon renal tumor included in the complex group of the
      embryologics or nefroblastics renal tumors. Generally occurs in young females and
      usually has excellent prognosis. It's important to differentiate of malignant
      variants, particularly renal cell papillary carcinoma, metanephric adenosarcoma
      and adult Wilms tumor. The suspicion and intraoperative analysis of the tumor can
      to facilitate the use of conservative renal surgery in order to avoid unnecessary
      radical and aggressive surgery. To exist cases of metastatic metanephric adenoma,
      and the totally benign characteristic of the metanephric adenoma and the
      malignant potential isn't totally clarify.

PMID- 12508463
TI  - [Urethral prolapse following physical effort. Surgical repair].
AB  - We want to present an urethral prolapse, in an elderly woman, after a physical
      effort. This situation is rarely reported in the literature, being a more common
      situation in children and premenarchal girls. The most common presentation is
      genital mass and bleedding. If it is a large one can become strangulated and
      urinary symptoms are present as acute urine retention. We want to describe the
      surgical treatment.

PMID- 12508464
TI  - [Obstructive anuria secondary to uterine prolapse].
AB  - The prevalence of obstructive uropathy linked to uterine prolapse ranges between
      4% and 80%, depending on the series, probably due to the varying degree of
      severity of the prolapses under consideration. Renal failure or anuria is an
      unusual complication. Several etiopathogenic theories regarding obstructive
      uropathy secondary to prolapse have been put forward: ureteral compression by the
      uterine vessels, severe urethral angulation, ureteral compression against levator
      ani muscles and the elongation and narrowing of the distal ureter. The major
      radiological exploration used in studying the urinary tract of these patients is
      intravenous urography in bipedestation. Emergency treatment for obstructive
      anuria resulting from a uterine prolapse consists of manually replacement of the
      prolapse. Surgery is considered to be the definitive ideal treatment, although in
      the case of surgical or anaesthetic high risk patients, inserting a permanent
      pessary may constitute a satisfactory solution. We present a case of obstructive
      anuria resulting from uterine prolapse, which was successfully treated with the
      insertion of a ring pessary.

PMID- 12508465
TI  - [Strangulation of penile base by metallic rings].
AB  - We report two cases of patients who went to the emergency department complaining
      of penile strangulation due to metallic rings (Double key ring) at the base of
      the penis which was resolved by cutting the metallic rings. We look trough the
      scientific literature about this unusual pathology and its management.

PMID- 12508466
TI  - [Superficial cancer of the bladder: 2 different types of frequently mixed up
      tumors].

PMID- 12508467
TI  - [Genetically modified food (food derived from biotechnology): current and future
      trends in public acceptance and safety assessment].
AB  - Current and future trends regarding genetically modified (GM) crops and food
      stuffs were reviewed, with a particular focus on public acceptance and safety
      assessment. While GM foods, foods derived from biotechnology, are popular with
      growers and producers, they are still a matter of some concern among consumers.
      In fact, our recent surveys showed that Japanese consumers had become uneasy
      about the potential health risks of genetically modified foods. Many Japanese
      consumers have only vague ideas about the actual health risks, and they appear to
      be making decisions simply by rejecting GM food because of non-informed doubts.
      Although the debate about GM foods has increased in the mass media and scientific
      journals, few articles concerning direct studies on the potential toxicity or
      adverse health effects of GM foods have appeared. The roles of relevant
      international regulatory bodies in ensuring that GM crops and food are safe are
      therefore have summarized. Finally, the current debate on use of GM crops in
      agriculture and future trends for development of GM foods with enriched
      nutrients, better functionality, and medicinal ingredients, which will be of
      direct benefit to the consumer, are covered.

PMID- 12508468
TI  - [Effects of home visitation by nurses around one month after delivery focus on
      mother's anxiety and awareness of child rearing problems].
AB  - PURPOSE: We evaluated the effects of home visitation by nurses around one month
      after delivery, focusing on mother's anxiety and awareness of child rearing
      problems. METHOD: We selected mothers who had a normal first child, and assigned
      them to the intervention (n = 131) or control (n = 100) groups. For the former,
      home visits were made by nurses, and for the controls, the usual care was
      provided. Outcome measurements were conducted before the intervention (Time I)
      and two months after (Time II). Usual care (neonatal home visiting service) was
      commonly provided by city health department, but not all subjects received a
      visit. We excepted the subjects who were provided with this usual care, analyzing
      the remaining subjects in the two groups. RESULTS: The eligible subjects of the
      intervention group were 64 mothers (48.9%) and in the control group were 66
      mothers (66%). There were no significant difference in terms of Time I
      demographic characteristics and outcome measures between two groups. However,
      there were significant differences in outcomes (mother's anxiety and awareness)
      between the two groups by ANCOVA, the intervention group showed decline of
      anxiety (P = 0.04) and improved enjoyment of child rearing (P = 0.02). Almost all
      mothers of the intervention group expressed the opinion that home visits by
      nurses were useful for themselves. CONCLUSION: We suggest that nurse home
      visitation around one month after delivery is useful to provide formal support
      for mother childcare.

PMID- 12508469
TI  - [Effects of cytotoxin-associated gene a (CagA) antibodies with Helicobacter
      pylori infection and lifestyle on chronic atrophic gastritis].
AB  - OBJECTIVE: We conducted a population-based study to examine differences in risk
      of developing chronic atrophic gastritis in association with Helicobacter pylori
      (H. pylori) infection, with and without the presence of cytotoxin-associated gene
      A (CagA) antibodies, as well as to determine associations with the lifestyle
      factors. METHOD: Seventy hundred and thirty eight residents (295 men and 443
      women) aged 30-64 living in a village in the southern part of Fukuoka Prefecture
      had an annual health checkup, and all participated in our study. We obtained
      information on their lifestyle with informed consent and measured the levels of
      serum pepsinogen I (PGI) and pepsinogen II (PGII), H. pylori and CagA antibodies.
      Chronic atrophic gastritis was defined as both PGI < 70 micrograms/l and PGI/PGII
      < 3.0. RESULTS: The odds ratios for development of chronic atrophic gastritis
      were 4.26 (95% CI, 2.22-8.17) for CagA-positive H. pylori infection and 3.87 (95%
      CI, 1.95-7.68) for CagA-negative H. pylori infection in males, and 4.92 (95% CI,
      3.06-7.92) and 3.02 (95% CI, 1.69-5.41) respectively for females, as compared
      with H. pylori-negative subjects. Regarding the relationship between chronic
      atrophic gastritis and lifestyle factors, high consumption of green tea was found
      to be negatively associated with risk, particularly with CagA-positive H. pylori
      infection. CONCLUSIONS: Our results suggest that a CagA-positive H. pylori
      infection is associated with an elevated risk for developing chronic atrophic
      gastritis as compared with Cag-negative H. pylori infection.

PMID- 12508470
TI  - [Relationship between self-management behavior and cognitive skills in type 2
      diabetes mellitus patients].
AB  - OBJECTIVES: The relationship between general self-management skill (SMS) and
      specific SMS, and associations with self-management behavior were investigated in
      diabetes patients. METHODS: A total of 306 diabetes patients were asked to
      complete questionnaires and additional information was collected from medical
      records. The contents of the questionnaires covered attributes, the SMS scale
      developed by Takahashi, the specific SMS score (diabetes skills score), and self
      management behavior, referring to items of Yasukata's and Kinoshita's scales.
      RESULTS: 1. The SMS scale correlated with the diabetes skills score, although
      high values were observed for the latter, and these skills influenced self
      management behavior. 2. Path analysis was applied to examine association between
      cognitive skills and self-management behavior. The results showed direct
      associations between self-management behavior and the SMS scale, the diabetes
      skills score and the presence or absence of a job. The SMS scale, the degree of
      knowledge, family support, and the presence or absence of a job were indirectly
      associated with self-management behavior through the diabetes skills score. The
      standardized partial regression coefficient (beta) showed self-management
      behavior to be much more related to the diabetes skills score than the SMS scale.
      CONCLUSION: These findings suggest that support of cognitive skills related to
      diabetes may be effective for improvement of the self-management behavior of
      diabetes patients.

PMID- 12508472
TI  - [Provider training for behavioral weight control intervention].

PMID- 12508471
TI  - [Symptoms of sick house syndrome and contributory factors; study of general
      dwellings in Hokkaido].
AB  - OBJECTIVE: The aim of this study was to clarify the "Sick House Syndrome" which
      has recently received increasing attention, and to investigate relationships
      between symptoms and the state of general dwellings in Hokkaido. METHODS:
      Questionnaires were sent to residents in 1775 dwellings, mainly solitary houses
      built or remodeled within the past few years by 24 construction companies in
      Sapporo and its environs, and answers was received from 564. The questionnaires
      included queries about building structure and characteristics, the residents'
      habits in the home, and subjective symptoms. We requested one resident who had
      the most severe symptoms in the dwelling to answer a questionnaire about
      symptoms. We classified the symptoms into 11 categories, and selected those that
      developed or were aggravated after the building or remodeling. We defined
      dwellings in which inhabitants complained of one or more categories of symptoms
      as the group with sick-house-related disease (developed or aggravated group: DA
      group), and those in which the inhabitants complained of two or more symptoms as
      the group with sick house syndrome (more than one organic symptom group: MO
      group)". Associations between symptoms and dwellings were then studied. RESULTS:
      There were 201 dwellings for which residents complained of symptoms (37.2%). Of
      these, 94 were in the DA group (16.7%), and 57 (10.1%) in the MO group. The
      symptoms that developed or were aggravated after building or remodeling of the
      dwellings were throat, 7.1%, dermal, 6.9%, psychoneural, 5.3%, eye, 5.1%, and
      nasal problems, 4.1%. Unpleasant odors form furniture were significant in both
      groups (DA: crude odds ratio (OR) 2.66, MO: OR 3.24). Use of aromatics was
      significant in group DA (OR 1.78). Condensation on windows and mold growth in the
      dwellings were significant in both groups (condensation on windows; DA: OR 2.98,
      MO: OR 3.32, mold growth; DA: OR 3.11, MO: OR 3.24). In addition, the percentage
      of dwellings for which residents complained of symptoms increased with signs of
      dampness (condensation on windows and mold growth). On logistic regression
      analysis, condensation on windows and mold growth were significant in both
      groups, and unpleasant odors from furniture in the MO group. CONCLUSION: It is
      suggested that symptoms of sick house syndrome are associated with high humidity
      such as condensation on windows and mold growth, odors from furniture and use of
      aromatics.

PMID- 12508473
TI  - [Prevalence and clinical characterization of Coxiella burnetii infection in
      patients with protracted low-grade fever].
AB  - We report here a persistent form of Coxiella burnetii infection. There have been
      no prospective surveys of chronic C. burnetii infection reported in Japan. Until
      recently, it was not possible to distinguish between previous and current
      infection with serological tests for antibody to C. burnetii. The nested PCR
      method, however, allows us to appreciate the current infection by detecting C.
      burnetii DNA with high sensitivity. Inoculation method using an A/J mouse was
      performed to confirm the viability of C. burnetii. To obtain an approximation of
      the prevalence of C. burnetii infection in the general population, we evaluated a
      random sample of patients with symptoms of continuous low-grade fever for one
      month or more. Analysis of 54 subjects with protracted debility and fatigue
      symptoms identified 13 subjects as carriers of C. burnetii (24.1%). There were no
      significant differences in age, C-reactive protein levels (0.69 +/- 1.19 mg/dl),
      white blood cell counts (6,089 +/- 2,189/microliter), eosinophil (3.4 +/- 3.6%)
      between the patients with C. burnetii infection and infection-free subjects. All
      thirteen patients had experienced protracted low-grade fever (up to 37.5 degrees
      C) for four months to seven years (30.5 +/- 27.7 months). Transthoracic
      echocardiography showed no evidence of endocarditis, or echosonography revealed
      no abnormal findings in the liver or kidneys. Although domestic animals
      constitute an important reservoir of C. burnetii, only two of the positive
      subjects had direct contact with them and none of the positive subjects were
      occupationally exposed to farm animals or common sources of infection. None had a
      history of hospitalizations for pneumonia or hepatic disease. Interestingly, five
      of the thirteen patients had a history of consulting a psychiatrist, and
      furthermore, one had a history of several admissions in a psychiatric hospital
      due to chronic fatigue symptoms. Ten of the patients had a high IgE titer (> 295
      IU/ml), which shows a higher prevalence than in patients without C. burnetii
      (76.9%: 22.0%, P = 0.001). Four of them had markedly elevated IgE levels, in
      excess of 2,000 IU/ml. The mean value of IgE was higher in the patients with C.
      burnetii infection than in infection-free subjects (1,388 +/- 1,706: 533 +/- 913
      IU/ml, p < 0.045). Two subjects were rheumatoid factor positive and another three
      had autoimmune thyroiditis. Twelve of the 13 subjects provided written informed
      consent for treatment with minocycline (200 mg/day). One month later, all subject
      became asymptomatic and apyretic (37.1 +/- 0.43 degrees C to 36.7 +/- 0.56
      degrees C; p < 0.025), and nested PCR did not identify C. burnetii DNA in serum
      samples. It should be noted that persistent symptoms including low-grade fever
      were observed for two weeks after the start of medication. Furthermore, three
      patients had persistent symptoms, and DNA detection by the nested PCR method
      became positive in all three patients within a few months.

PMID- 12508474
TI  - [Presence of the genes regarding adherence factors of Escherichia coli isolates
      and a consideration of the procedure for detection of diarrheagenic strain].
AB  - Diarrheagenic Escherichia coli are differentiated from non-pathogenic members
      with enterotoxin production, enteroinvasiveness and serotyping. However, the
      serotypic members are rarely sufficient to reliably identify a strain as
      diarrheagenic on E. coli. Recently, there are many definite articles which the
      adhesive E. coli strain against intestinal epithelial cells is enterovirulent. In
      this study, 1,748 E. coli isolates of diarrheagenic and non-diarrheagenic
      categories which belonged to EHEC, ETEC, EIEC EPEC and non-EPEC were examinated
      by PCR method for the presence of eaeA, aggR and bfpA regarding adherence factor
      genes, and astA of EAST1. The strains examined were recognized to variable
      carrying geno-patterns, and a large number of EHEC, EPEC and non-EPEC had carried
      either eaeA or aggR genes. In EHEC isolates, a carrying pattern with the most
      high frequency was only eaeA, and this type was recognized in the isolates of
      serotype O157, O26 and O111. EPEC and non-EPEC isolates were recognized eaeA or
      aggR which harboring with astA or not. Of 508 EPEC isolates from human, a total
      of 137 isolates (27.0%) carried aggR, and a total of 74 isolates (14.6%) had
      eaeA, while of the 91 isolates from non-human were recognized aggR and eaeA with
      2.2% (2 isolates) and 12.1% (11 isolates), respectively. Also, of 266 non-EPEC
      isolates from human, a total of 16 isolates (6.0%) carried aggR, and a total of
      58 isolates (21.8%) had eaeA. On the other hand, 22 (7.0%) of 316 isolates
      examined from non-human had eaeA, however no isolate had aggR. Thirteen isolates
      of EIEC and 218 ETEC isolates were screened, and only 6 ETEC isolates had either
      eaeA or aggR. The astA gene was recognized in the isolates of all categories, and
      ETEC strains had more frequently. The bfpA gene was recognized with more
      frequently in a serotype O157: H45, which is obtained from human with diarrhea,
      however, this strain was not recognized a member of the EPEC serotype. There is
      no diagnostic system for the strain of E. coli that cause diarrheal diseases,
      therefore more laboratories are unable to identify them. The authors had
      confirmed which PCR technique is a useful simple and rapid method for the
      detection of adherence factor genes on E. coli strains. From the these results,
      we showed a differentiation method using PCR technique which have relation with
      adherence factor, enterotoxin-production and invasiveness, and we firmly believe
      that application of the procedure is a reasonable and useful method for the
      identification of diarrheagenic E. coli.

PMID- 12508475
TI  - [Usefulness of multiplex-PCR for identification of Entamoeba histolytica and
      Entamoeba dispar].
AB  - We evaluated the usefulness of a multiplex-PCR method for differentiation of
      Entamoeba histolytica and Entamoeba dispar, which are morphologically
      indistinguishable species. Cultured trophozoites of E. histolytica HM-1: IMSS and
      E. dispar SAW were used as the positive control. Seven human fecal samples, from
      which E. histolytica-like cysts were detected by microscopic examination, and
      three intestinal protozoan parasites, Cryptosporidium parvum HNJ-1, Giardia
      intestinalis Portland-1, and Blastocytis hominis Nand II, were used for the
      evaluation of sensitivity and specificity of the PCR method. The other PCR
      method, which has been used for the diagnosis of amebic infections in Japan, was
      also performed by using the same samples for the evaluation. In comparison with
      the conventional PCR method, the multiplex-PCR showed 1) higher sensitivity, 2)
      the size of diagnostic fragments of PCR products was clearly different in both
      Entamoeba species, 3) it was possible to perform PCR using a single tube per
      sample, and then to save the amount of DNA polymerase, 4) no diagnostic
      amplification products were found in other intestinal protozoan parasites, and 5)
      E. histolytica specific fragment was amplified in all clinical samples examined.
      In conclusion, it is considered that the multiplex-PCR method is a useful tool
      for detection of both Entamoeba species DNA from fecal samples and for the
      distinction between E. histolytica and E. dispar.

PMID- 12508476
TI  - [Faropenem 300 mg 3 times daily versus levofloxacin 100 mg 3 times daily in the
      treatment of urinary tract infections in patients with neurogenic bladder and/or
      benign prostatic hypertrophy].
AB  - Faropenem (FRPM) is an only penem antibiotics. Though it has been reported that
      FRPM had good efficacy (overall efficacy rate: 82.0%) against patients with
      complicated urinary tract infection, FRPM has not been frequently used for UTI
      patients. This multicenter clinical study was designed to compare FRPM 300 mg 3
      times daily to Levofloxacin (LVFX), which is the standard treatment for patients
      with UTI, 100 mg 3 times daily for 7 days in the treatment of urinary tract
      infections in patients with neurogenic bladder and/or benign prostatic
      hypertrophy. A total of 60 patients with significant bacteriuria and pyuria were
      included in this study. Overall efficacy rate (excellent plus moderate) was
      achieved in 90.6% (29/32) of patients treated with FRPM versus 82.1% (23/28) of
      those treated with LVFX. The ratios of eliminated bacteriuria and cleared pyuria
      were 71.9% and 56.3% of patients treated with FRPM, and 64.3% and 75.0% of those
      treated with LVFX. These data were not significant difference. In conclusion,
      FRPM 300 mg 3 times daily is at least as effective as LVFX 100 mg 3 times daily
      in patients with complicated urinary tract infection.

PMID- 12508477
TI  - [Antibacterial activity of new-quinolone and macrolide antibiotics against oral
      bacteria].
AB  - Minimum Inhibitory Concentration (MIC) of 4 new-quinolone antibacterial reagents
      and 4 macrolide antibiotics against periodontopathic bacteria 21 species 24
      strains of standard strains including oral related bacteria and clinical isolated
      (1993-1999) 20 strains of Porphyromonas gingivalis, 7 strains of Actinobacillus
      actinomycetemcomitans were determined. Minocycline HCl was used as the
      comparative reagent. Macrolide showed moderate antibacterial activity against
      standard strains of oral related bacteria except Fusobacterium nucleatum. New
      quinolone showed excellent activity against Eikenella corrodens and
      Actinobacillus actinomycetemcomitans. Concerning to the clinical isolated
      strains, Clarithromycin effected P. gingivalis (MIC90 0.1 microgram/ml) and
      Levofloxacin and Ciprofloxacin showed high-potency antibacterial activity against
      clinical isolated Actinobacillus actinomycetemcomitans (MIC90 0.013-0.025
      microgram/ml).

PMID- 12508478
TI  - [Effectiveness of oseltamivir treatment against influenza type A and type B
      infection in children].
AB  - We investigated the effectiveness of oseltamivir treatment against influenza
      virus infection in children. We treated 131 patients (mean age, 5.8 +/- 3.6
      years) with oseltamivir (4 mg/kg/day for 5 days) during the 2001-2002 epidemic.
      All of the patients had been diagnosed with influenza using a rapid diagnosis
      kit. When treatment was initiated within 48 hours of the onset of fever, 44% of
      the patients became afebrile (< 37.5 degrees C) within one day, and 86% of them
      recovered within two days. The average duration of fever after the initiation of
      oseltamivir treatment was 1.7 days. Oseltamivir was equally effective against
      both influenza type A and type B. No differences in the effectiveness of
      oseltamivir treatment were observed between young children (< 4 years of age) and
      school-aged children (> 6 years of age). No obvious side effects were observed.

PMID- 12508479
TI  - [3 dengue fever cases, infected during a group tour to the Philippines].
AB  - We report three dengue fever cases, infected during a group tour to the
      Philippines. A 58-year old male experienced sudden onset of high fever 5 days
      after returning to Japan, followed by rash and thrombocytopenia. The other 2
      cases experienced similar symptoms. Clinically suspected from the travel history,
      incubation time and the state of dengue fever epidemic in the Philippines, dengue
      virus infection was confirmed by the laboratory tests. The incidence and
      geographical distribution of dengue virus infection have greatly increased in
      recent years. There have been reports of Japanese travelers who visited dengue
      endemic countries, infected and developed symptoms after returning home. Dengue
      virus infection should be included in the differential diagnosis of the patients
      who develop high fever and rash after returning from tropical areas.

PMID- 12508480
TI  - [A case of bacteremic group A streptococcus infection with organ dysfunction
      following a minor skin abrasion].
AB  - A 20-year-old male was admitted to our hospital with the chief complaints of high
      fever and pain around his right hip joint. He had his right knee injured with a
      slight abrasion three weeks before. The diagnosis of suppurative lymphadenitis of
      inguen was made, and intravenous cefotiam was started. Despite these treatments
      his fever continued, general edema and dry cough appeared. Arterial blood gas
      showed severe hypoxia and chest X ray revealed marked cardiomegaly associated
      with ground-glass opacity over bilateral lower pulmonary fields. Slight renal
      insufficiency was also observed. On the fifth hospital day, the culture specimens
      of both blood and pus from the abrasion on admission yielded Streptococcus
      pyogenes. His condition was diagnosed as severe group A Streptococcus infection,
      then antibiotics were switched to intravenous administration of high dose
      aminobenzyl penicillin and clindamycin in combination with protease inhibitor,
      urinastatin. After these treatments, his condition improved and he was discharged
      from the hospital after one month. Group A Streptococcus may cause uncommon but
      life-threatening infection such as septicemia. Early recognition of the disease
      and prompt initiation of appropriate treatment may lead to successful outcome.

PMID- 12508481
TI  - [Human parvovirus B19 infection which first presented with petechial hemorrhage,
      followed by papular-purpuric gloves and socks syndrome and erythema infectiosum].
AB  - A case of human parvovirus B19 (B19) infection is reported. A 6-year-old
      previously healthy girl was admitted to our hospital complaining of slight fever
      and petechial hemorrhage on her neck, trunk and the proximal parts of
      extremities. On admission, the platelet count was within normal range (180 x
      10(3)/microliter) but white blood cells and reticulocytes were moderately
      suppressed (2.4 x 10(3)/microliter and 1@1000, respectively). The purpura
      disappeared in a week and the blood cell counts fully recovered without any
      specific treatment. Detection of B19 DNA and anti-B19 IgM antibody in the serum
      on admission led to the final diagnosis. Since the cellular receptor for B19, the
      blood group P antigen, is expressed on vascular endothelial cells as well as
      erythroid progenitor cells, the purpura was considered to be the result of direct
      vascular injury. She was very unique as she subsequently exhibited papular
      purpuric gloves and socks syndrome and erythema infectiosum during follow-up.
      This case may provide a new insight into the pathogenesis of cutaneous
      manifestations of B19 infection.

PMID- 12508482
TI  - [Development of a gene therapy system for leukemia using a novel ribozyme].

PMID- 12508483
TI  - [DAD, new intensive chemotherapy for patients with myeloma: a preliminary
      report].
AB  - A new intensive chemotherapy regimen, DAD, composed of doxorubicin, melphalan and
      dexamethasone, was given to 17 patients with multiple myeloma. The end point of
      this regimen was to obtain a deep posttreatment nadir in the M-protein levels so
      as to increase the chance of plateau attainment which would be associated with
      prolonged survival in each patient. It was noteworthy that all the 17 evaluable
      patients achieved a partial response. Nine of the 17 (52.9%) attained a plateau.
      Ten of the 17 patients (58.8%) obtained a deep posttreatment nadir in their M
      protein levels (IgG < 2,000 mg/dl, IgA < 1,000 mg/dl, BJP = 0 g/dl/day), and six
      of them reached a plateau phase, which was not significantly more frequent than
      those who did not obtain a deep posttreatment nadir in their M-protein levels
      (three of seven reached plateau phase). The median survival of the 17 patients
      (37.6 months) was significantly prolonged compared with that of patients treated
      with our previous chemotherapy regimens, VMCP (22.5 months) and MMPP (23.5
      months), and was comparable to that of MMCP (29.5 months).

PMID- 12508484
TI  - [Nasal NK cell lymphoma with hemophagocytic syndrome developed tumor lysis
      syndrome after CHOP therapy].
AB  - A 24-year-old man was admitted with fever and rhinostenosis. A bulky mass was
      observed in his left nasal cavity. A biopsy showed diffuse proliferation of large
      atypical lymphocytes, which were positive for CD45RO, CD56, MIB-1, and EBER. Bone
      marrow aspiration showed many histiocytes with active hemophagocytosis. A
      diagnosis of nasal NK cell lymphoma with hemophagocytic syndrome (clinical stage
      IVB) was made. Following CHOP regimen chemotherapy, the tumor transiently reduced
      in size, but the patient developed multiple organ failure possibly due to tumor
      lysis syndrome. His general condition was improved by intensive supporting
      therapy. Two weeks later, the tumor again got worse. Despite salvage chemotherapy
      with a P-IMVP16/CBDCA regimen, the patient died of multiple organ failure due to
      tumor lysis syndrome. Autopsy revealed diffuse necrosis and fibrosis without
      proliferation of lymphoma cells in the liver, spleen, bone marrow, and lymph
      nodes. During the clinical course, hypercytokinemia including soluble IL-2
      receptor, interferon-gamma and IL-18 was observed. The poor prognosis of NK/T
      cell lymphoma might be associated with massive tissue damage with
      hypercytokinemia.

PMID- 12508485
TI  - [Successful treatment with fludarabine of chronic lymphocytic leukemia associated
      with nephrotic syndrome].
AB  - We successfully treated a patient with chronic lymphocytic leukemia (CLL)
      associated with a nephrotic syndrome. An 82-year-old man had been diagnosed as
      having CLL and been under observation for a year without treatment. In January,
      2001, he developed hypoprotenemia, proteinurea, and edema in the extremities and
      face. With the exacerbation of the symptoms, he was admitted to our hospital in
      March of the same year. Under the diagnosis of nephrotic syndrome with CLL, the
      patient underwent induction therapy for CLL with fludarabine (13 mg/m2/day for 4
      days), which brought about a complete remission of CLL and the disappearance of
      the edema. To our knowledge, this was the first case in Japan where fludarabine
      was dramatically effective in treating both CLL and the nephrotic syndrome. This
      result indicated that fludarabine is beneficial for not only CLL but also
      complications like nephrotic syndrome.

PMID- 12508486
TI  - [Successful treatment with G-CSF and corticosteroid of adult idiopathic
      autoimmune neutropenia presenting as recurrent enterocolitis].
AB  - A 63-year-old woman had previously been admitted to another hospital due to
      fever, abdominal pain and diarrhea. She was treated with fasting, antibiotics and
      G-CSF administration because of the coexistence of neutropenia, and the symptoms
      improved. However, discontinuation of G-CSF administration resulted in a
      recurrence of the neutropenia accompanied with enterocolitis. After admission to
      our hospital, a diagnosis for idiopathic AIN was performed as she tested positive
      in both granulocyte immunofluorescence and granulocyte agglutination tests.
      Administration of corticosteroid following G-CSF resulted in a continuous
      increase in the neutrophil count and the disappearance of anti-neutrophil
      autoantibodies.

PMID- 12508487
TI  - [Localized recurrence of acute lymphoblastic leukemia-L3 in the tonsil after 3
      years' remission].
AB  - Recurrence of Burkitt's lymphoma (BL)/acute lymphoblastic leukemia (ALL)-L3 after
      a long-term remission is very rare. We herein report on a case of BL/ALL-L3
      indicating solitary recurrence in the tonsil after a 3-year remission. A 50-year
      old man was diagnosed as having Burkitt's type ALL-L3 with involvement of the
      stomach and abdominal lymph nodes. He was treated with intensive chemotherapy
      consisting of methotrexate and cyclophosphamide (ALL-BFM86 protocol), and a
      complete remission was achieved. After sustaining the remission for three years,
      a swelling of the right tonsil was observed, which was histologically diagnosed
      as Burkitt's lymphoma. No other organ involvement, including the bone marrow, was
      observed. The pattern of c-myc rearrangement of the tonsil demonstrated by
      southern blotting was identical to that of the bone marrow at initial
      presentation and the recurrence of primary ALL-L3/BL was thus confirmed. The
      patient was then treated with the ALL-BFM86 protocol and subsequently underwent
      high-dose chemoradiotherapy with autologous peripheral blood stem cell
      transplantation (PBSCT). He has now been in complete remission for more than 2
      years after his PBSCT.

PMID- 12508488
TI  - [Intradural recurrence of multiple myeloma during the hematological complete
      remission].
AB  - In December 1997, a 55-year-old man presented with left-sided back and arm pain.
      Pretreatment examination revealed IgG-lambda type M-protein, Bence-Jones protein
      and the posterior mediastinum tumor. Bone marrow examination revealed
      hypercellular marrow with 73.6% plasma cells. He was diagnosed as having multiple
      myeloma with extramedullary lesion. As a result of VAD, MP, interferon and
      radiation therapy, he had a hematological complete remission. After 21 months, he
      developed intradural relapse at cauda equina and cerebrum. Many plasma cells and
      IgG-lambda type M-protein were detected in the cerebrospinal fluid. Laboratory
      examinations showed a complete remission except for cerebral and meningeal
      involvement. The myeloma cells might have infiltrated the intradural space at
      diagnosis and expanded in the central nervous system despite chemotherapy.
      Because reported cases with cerebral and meningeal myeloma are increasing
      according to the recent advance of treatment, we must pay attention to the
      meningeal myeloma.

PMID- 12508489
TI  - [Persistent T-cell mixed chimerism in a case of malignant lymphoma after
      nonmyeloablative allogeneic peripheral blood stem cell transplantation].
AB  - We describe a 51-year-old woman with recurrent follicular lymphoma from the age
      of 47 despite chemo-radio therapy, who subsequently underwent nonmyeloablative
      stem cell transplantation with conditioning consisting of fludarabine and low
      dose total body irradiation (2 Gy). Myelosuppression was very mild, so the
      patient required no transfusions. Chimerism analysis from peripheral blood showed
      that T-cell mixed chimerism continued over 12 months after stem cell
      transplantation (the percentage of recipient T-cells was approximately 20%).
      Despite this, the lymphadenopathy disappeared, and the patient developed grade II
      acute GVHD (graft versus host disease). It has been considered that the
      establishment of full donor chimerism is required to induce GVHD and GVM (graft
      versus malignancy) effects. In this case, however, an allo-response was observed
      despite the persistence of T-cell mixed chimerism.

PMID- 12508490
TI  - [Small lymphocytic lymphoma during the course of pure red cell aplasia].
AB  - A 29-year-old woman was diagnosed as having pure red cell aplasia (PRCA) in 1983.
      Her serum and IgG inhibited erythroid colony formation of bone marrow cells from
      a normal individual, suggesting antibody-mediated suppression of erythropoiesis.
      She was first successfully treated with corticosteroids, azathiopurine and
      cyclophosphamide. However, she relapsed in 1995 and her anemia became refractory
      to immunosuppressive therapy. In 1998, she developed systemic lymph node
      enlargement and was diagnosed as having B-cell small lymphocytic lymphoma.
      Combination chemotherapy resulted in regression of the lesion, but failed to
      improve the anemia. In this patient's case, we can speculate that B cells
      producing autoantibodies against erythroid cells have undergone transformation,
      or alternatively that the immunosuppressive state caused by the PRCA therapy
      promoted generation of a neoplastic B cell clone.

PMID- 12508491
TI  - [Considerations in breast imaging diagnosis].
AB  - Certain points regarding breast imaging diagnosis are open to interpretation and
      are considered difficult to understand in the short course on mammography. For
      example, focal asymmetric density (FAD) may or may not include mass lesions. To
      assess whether FAD includes mass lesions or not, a comparison of density with
      equal gland volume, margins, and internal structure is important. Calcifications
      must be read carefully according to shape and distribution. The shapes of
      calcifications can be used to estimate the intra-ductal structure of breast
      cancer, but small round calcifications and amorphous calcifications can be
      interpreted as both benign and malignant lesions. Therefore, distribution brings
      important information to the assessment. Architectural distortion can be caused
      by fibrosis in both benign and malignant lesions. Lobular carcinoma and scirrhous
      carcinoma are the most common malignant diseases, but radial scar, inflammatory
      disease, and surgical scar need to be considered in the differential diagnosis.
      Finally, the pathological assessment of breast cancer and mammographic technology
      are basic, important factors in reading mammography.

PMID- 12508492
TI  - [Diagnosis of deep vein thrombosis using multi-detector helical CT].
AB  - PURPOSE: To evaluate the usefulness of multi-detector helical CT (MDHCT) with
      contrast medium in the diagnosis of deep vein thrombosis (DVT). MATERIALS AND
      METHODS: The bilateral veins of the dorsal pedis in 45 patients (12 men, 33
      women; average age, 64 years) under clinical suspicion of DVT were first
      punctured using 22-G needles. Then CT scanning from the level of the foot to the
      inferior vena cava was started 20 sec after the initial injection of 200 mL of
      dilute contrast medium (50 mL nonionic iodinated contrast medium of 300 mgI/mL
      and 150 mL saline) at a rate of 5 mL/sec. RESULTS: Two patients were excluded
      because of unsuccessful venous puncture. The average scanning time in 43 patients
      was 38.5 +/- 7.9 seconds. Images of veins from the foot to the inferior vena cava
      were clearly demonstrated in each case. MDHCT showed DVT in 32 cases and patent
      deep vein in 11 cases. Simultaneous venography of the lower extremity in 18
      patients clearly visualized DVT at the same level detected by contrast MDHCT.
      CONCLUSION: MDHCT for the diangosis of DVT has the advantages of wider scanning
      range, shorter scanning time, and finer Z-axis resolution than the other
      diagnostic modalities.

PMID- 12508493
TI  - [Evaluation of the results of radiotherapy for carcinoma involving the external
      auditory canal or middle ear].
AB  - PURPOSE: To evaluate the results and significance of radiotherapy for carcinoma
      involving the external auditory canal or middle ear. MATERIALS AND METHODS: Six
      patients underwent radiotherapy. Five patients had squamous cell carcinoma and
      one had ceruminous adenocarcinoma. In addition to radiotherapy, two patients
      underwent complete resection, and the other patient underwent incomplete
      resection. Total radiation doses ranged from 30 to 88 Gy (2 Gy/fraction, 5
      fractions/week). RESULTS: The post-treatment survival period ranged from 8 months
      to 7 years (mean, 3 years, 11 months). Two patients treated by radiotherapy alone
      (doses of more than 60 Gy) lived for more than five years. CONCLUSION: The
      prognosis of patients with advanced cancer involving the external auditory canal
      and middle ear is generally poor. Based on even this limited clinical experience,
      a tumor dose of at least 70 Gy should be delivered for local control of advanced
      cancer. To avoid complications, several plans such as application of the
      shrinking field technique are recommended.

PMID- 12508494
TI  - [Sentinel lymph node after intramammary injection of superparamagnetic iron
      oxide].
AB  - The purpose of this study was to evaluate enhancement (signal loss) of the
      axillary lymph nodes on MR lymphography after intramammary injection of
      superparamagnetic iron oxide (Ferumoxides) for detection of the sentinel lymph
      node. MR lymphography was performed in a total of 11 patients with breast cancer
      without palpable axillary lymph node swelling before operation. Coronal and axial
      images were obtained before and after intramammary injection of 1.5 ml
      Ferumoxides adjacent to the breast tumor. In all patients, decreased intensity
      was recognized in the axillary lymph nodes. MR lymphography could detect the
      sentinel lymph node with its decreased signal intensity 20 minutes after the
      intramammary injection of Ferumoxides.

PMID- 12508495
TI  - Ectopic thymus presenting as neck mass.
AB  - A 3-month-old girl presented with an asymptomatic soft tissue mass in the right
      neck. Her preoperative data were normal. CECT of the neck showed a 3-cm solid
      mass with homogeneous mild enhancement without mass effect. CECT of the thorax
      showed a normal thymus. MR images showed a right submandibular mass with signal
      intensity identical to that of the mediastinal thymus. Although it was difficult
      to make a correct preoperative diagnosis, surgical microscopic examination
      demonstrated normal thymic tissue. Because ectopic thymus can occasionally
      present with life-threatening symptoms, and malignant transformations have been
      documented, complete excision of cervical ectopic thymus was advocated.

PMID- 12508496
TI  - [A fatal case of anaphylactoid shock after administration of nonionic contrast
      medium].
AB  - We report a case of fatal anaphylactoid shock caused by a CT examination using
      nonionic contrast medium. A 79-year-old female patient was diagnosed with right
      recurrent nerve plasy. There was no known history of drug allergy or exposure to
      contrast medium. Approximately 50 seconds after contrast medium bolus injection
      began, the patient was noted to be apneic. Despite cardiopulmonary resucitation,
      the patient died. An autopsy demonstrated marked laryngeal edema and showed
      extensive mast cell infiltration.

PMID- 12508497
TI  - Partners in public health law: elected officials, health directors, and
      attorneys.
AB  - The partnership that has developed over the years between elected officials,
      health directors, and attorneys came about through necessity and practicality.
      This article examines this partnership and some of the conflicts and problems it
      contains. The article discusses the problems of overlap of authority between
      public health departments and elected officials. It also emphasizes that existing
      laws and regulations often provide sufficiently flexible authority, and that such
      laws and regulations can be exercised in new ways to address current public
      health problems. The article concludes with a discussion of the challenges faced
      by public health officials and legislators in forming a partnership to secure
      necessary financial support and legal authority for public health activities.

PMID- 12508498
TI  - How do we translate science into public health policy and law?
AB  - Scientific knowledge concerning effective preventive measures to preserve and
      protect the health of the public continues to grow exponentially. Methods for
      assessing the impact of population-based interventions such as policies and laws
      have also greatly increased in the past decade, including systematic approaches
      that allow general findings to be drawn from various studies, especially those
      developed as part of the Guide to Community Preventive Services (Community
      Guide). However, the translation of the collected scientific evidence gathered to
      date has been spotty and problematic. Success stories do exist, including
      community water fluoridation, a significant factor in improvements in reduction
      of tooth decay over the past 50 years. Even for interventions with a strong
      science base, such as community water fluoridation, significant barriers to
      implementation of effective strategies discovered through research remain.
      Barriers include public misunderstanding of health issues and proposed solutions
      such as fluoridation; lack of engagement on the part of the media in
      communicating known effective strategies; and reluctance on the part of
      policymakers to champion approaches that concern but may not be advocated by
      their constituencies. The increasing burden of chronic disease places public
      policymakers into non-traditional roles, such as advocating behavior change as a
      preventive measure. Science is a critical tool to help legislators and
      policymakers "connect the dots" between public policies. For example, the
      elimination or degrading of physical education programs in schools is an
      important factor in addressing the national epidemic of childhood overweight and
      obesity in addition to the increase in rates of Type II diabetes among children.
      This article provides an overview of the past, present, and future associated
      with translating science into public health policy and law, including a review of
      tools and strategies to address existing and expanding public health challenges.
      The article also provides and discusses examples of translating and implementing
      science-based solutions to address public health problems effectively.

PMID- 12508499
TI  - New perspectives on litigation and the public's health.
AB  - This article provides redacted versions of three presentations by distinguished
      individuals with long experience in litigation or regulation to protect the
      public's health. A central theme is the need to develop partnerships to promote
      protection efforts. Jan Schlichtmann is internationally recognized for his
      representation of eight Massachusetts families engaged in legal action against
      two major companies, W. R. Grace and Beatrice Foods, in a fight to obtain justice
      in a groundbreaking case that has been the subject of many press and journal
      reports along with a nationally best-selling book and motion picture titled A
      Civil Action. His inspiring story of a long and difficult struggle to uncover the
      truth about contaminants in drinking water caused by buried wastes and to bring
      public health authorities and others together in a partnership to address the
      problem is a model of the use of litigation tools to protect the public's health.
      Diana Bonta, Director of the California Department of Health Services, discusses
      the efforts of her department to ensure the integrity of the Medi-Cal program
      that her department administers and the proper uses of litigation, including
      decisions to avoid litigation, for the purpose of protecting the public's health.
      She focuses on regulatory and legal efforts to protect her state's citizens and
      their environment, with an emphasis on the use of common sense in making
      decisions about whether to litigate and on partnering with advisory groups and
      members of the public as a means of aiding her department's accomplishment of its
      mission. Finally, Sandy Praeger, a state senator from Kansas, discusses efforts
      to use the law and regulation for the purpose of protecting the Kansas River. She
      stresses the importance of using sound judgment, backed by assessment of the
      legislative and physical environments, to make the right decisions regarding the
      use of the law for public health protection. She also points out that sometimes
      one can use the legislative process as an alternative to litigation to get a
      message out and force a correct decision.

PMID- 12508500
TI  - When the law is good medicine.

PMID- 12508501
TI  - Do we need a new law or regulation? The public health decision process.
AB  - New laws or regulations may not be a practical response to a public health
      threat. While in some instances legislation or regulation may be the only
      alternative to protecting the public's health, in many situations public health
      authorities and their legal counsel must consider alternative approaches to
      abating threats. This article provides an overview of the alternatives available
      to the public health official by providing discussion of a "legal tool box"
      available to public health officials. It also presents scenarios, with
      commentary, that serve as the basis for illustration of other means of
      intervention.

PMID- 12508502
TI  - Building the legal foundation for an effective public health system.
AB  - Work has been underway nationally since the mid-1990s to equip state and
      community public health systems with the infrastructure needed to perform
      essential public health services. Key components of that infrastructure are a
      competent workforce, information and communication systems, health department and
      laboratory capacity, and legal authorities. As part of this transformative work,
      standards and assessment tools have been developed to measure the capacity and
      actual performance of public health systems. In addition, a number of states have
      examined the legal foundation for public health services and have revised and
      updated those authorities to improve their system's capacity in the context of
      evolving health challenges. Among those states are Nebraska, New Jersey, and
      Texas, all of which, beginning in 1999, have adopted dynamic new approaches to
      aligning public health's legal authorities with new missions and expectations for
      performance and accountability. This article describes the approaches that these
      three states have taken to strengthen their legal foundation for public health
      practice, to illuminate the perspectives legislators and health officials bring
      to the process, and to give decision makers in other states practical insight
      into the potential benefits of reviewing and restructuring public health's legal
      authorities. The underlying stimuli for the states' initiatives differed
      significantly, yet shared an important, common core. What they held in common was
      concern that outdated elements of the public health system and infrastructure
      hindrered delivery of essential public health services at the community level.
      Where they differed was in the type of tools they found most suitable for the job
      of rejuvenating those structures. The approaches taken, and the policy tools
      selected, reflect the unique health needs of each state, establish relationships
      among state and community health authorities and agencies, and provide guidance
      by elected and appointed policy makers. Each state continues to refine its
      approach as it gains experience with the new authorities.

PMID- 12508503
TI  - Legal preparedness for bioterrorism.
AB  - Responding to a terrorist biological weapon attack poses new challenges not only
      for the public health response community but also to the very construct of public
      health police powers as we know them today. States are debating the merits of
      revising and updating these powers in order to ensure an effective and legally
      appropriate response. This article covers three aspects of the policy debate: the
      experience in one state from a legislative perspective, a discussion from an
      academic viewpoint, and one example of the role of enhanced powers from the
      response perspective.

PMID- 12508504
TI  - The power to act: two model state statutes.
AB  - Enabling statutes for state and local public health agencies set forth their
      powers and duties and provide the legal basis for their work. Obsolescence,
      inconsistency, and inadequacy may render some public health laws ineffective or
      even counterproductive. Reforming state public health law can improve the legal
      infrastructure that supports public health systems in responding to bioterrorism
      and other public health threats. Two legal tools available to assist the process
      of establishing a strong legal foundation for public health practice are the
      Model State Emergency Health Powers Act, developed in 2001 by the Center for Law
      and the Public's Health, and the Model State Public Health Act, currently under
      development by the Turning Point Public Health Statute Modernization National
      Collaborative. These model acts can serve as guides for assessing current state
      public health law, and they provide example statutory language for use by those
      working to update their laws. That strong state public health law and model
      public health acts serve as resources for law reform is recognized by local
      health officials and state legislators as well as by state public health
      officials. Lessons learned from recent experiences with crafting and introducing
      legislation based on the Model State Emergency Health Powers Act can prove useful
      in the future to those working on public health law reform efforts in their
      states.

PMID- 12508505
TI  - Public health emergencies and the public health/managed care challenge.
AB  - The relationship between insurance and public health is an enduring topic in
      public health policy and practice. Insurers share certain attributes with public
      health. But public health agencies operate in relation to the entire community
      that they are empowered by public law to serve and without regard to the
      insurance status of community residents; on the other hand, insurers (whether
      managed care or otherwise) are risk-bearing entities whose obligations are
      contractually defined and limited to enrolled members and sponsors. Public
      insurers such as Medicare and Medicaid operate under similar constraints. The
      fundamental characteristics that distinguish managed care-style insurance and
      public health become particularly evident during periods of public health
      emergency, when a public health agency's basic obligations to act with speed and
      flexibility may come face to face with the constraints on available financing
      that are inherent in the structure of insurance. Because more than 70% of all
      personal health care in the United States is financed through insurance, public
      health agencies effectively depend on insurers to finance necessary care and
      provide essential patient-level data to the public health system. Critical issues
      of state and federal policy arise in the context of the public health/insurance
      relations during public health emergencies. These issues focus on coverage and
      the power to make coverage decisions, as well as the power to define service
      networks and classify certain data as exempt from public reporting. The extent to
      which a formal regulatory approach may become necessary is significantly affected
      by the extent to which private entities themselves respond to the problem with
      active efforts to redesign their services and operations to include capabilities
      and accountability in the realm of public health emergency response.

PMID- 12508506
TI  - Land use planning: why public health must be involved.
AB  - The way that land is used has a direct impact on public health. Legislators and
      other with responsibility for land use planning need to be aware of the public
      health connection and need to promote effective land use planning as a means of
      improving the public's health. This article discusses the public health/land use
      connection and the role that local, state, and national legislators can play in
      promoting land use planning that supports the public's health. It also provides
      an example of a collaborative local land use initiative aimed at addressing a
      public health problem in a city and at providing a model that other locations can
      use in making land use conform to sound public health policy. Finally, it
      provides an overview of initiatives to promote healthy land use in the New York
      metropolitan area by Regional Plan Association, a private non-profit planning
      organization.

PMID- 12508507
TI  - Clean indoor air: where, why, and how.
AB  - Clean indoor air policies are an effective way to eliminate exposure to second
      hand smoke and reduce smoking among youth and adults; they are strongly
      recommended by the Surgeon General and the Task Force on Community Preventive
      Services. How these policies are put into effect and at what level of government
      can make a difference. Legislation that preempts local action prevents
      communities from enacting more stringent laws or tailoring laws to address
      community-specific issues. Preemptive state laws also can be a barrier to local
      enforcement because communities not involved in decision making may be less aware
      of laws, may have no enforcement mechanism, and thus may be less complaint.
      Preemption is clearly a tobacco industry strategy to take away local control,
      usually in exchange for a weak law offering little protection from second hand
      smoke. As communities across the country continue to pass stronger local
      ordinances, eliminating preemptive laws becomes more important. During 2002,
      Delaware became the first state to repeal clean air preemption. In Iowa, the
      attorney general's office has been involved in the determination of whether the
      state clean air law prevents communities from passing more stringent ordinances.
      And although Minnesota's pioneer Clean Indoor Air Act does not preempt local
      laws, the debate over preemption there has not ended but instead has taken new
      forms.

PMID- 12508508
TI  - Policy tools for the childhood obesity epidemic.
AB  - The rapid increases in childhood and adolescent overweight between 1980 and 1999
      can only be explained by environmental factors. Historically, the most effective
      strategies to address nutritional problems that have caused such widespread
      disease have been policy-driven environmental changes. To develop effective
      public policy responses to the obesity epidemic, we must expand the science base
      linking environmental conditions and policies to health behaviors and conditions;
      establish effective intersectoral coalitions of stakeholders; and create
      effective policy at the national and state levels. Although the childhood obesity
      epidemic is still evolving, this article provides several examples of potentially
      effective strategic approaches to address it.

PMID- 12508509
TI  - Tobacco use: the impact of prices.
AB  - Cigarette smoking continues to be a leading cause of death in the United States,
      imposing substantial measurable costs to society. Smoking killed over 440,000
      people in the United States each year during the period 1995-1999. If current
      smoking trends continue, over 5 million people currently younger than 18 will die
      prematurely from tobacco-related diseases. Increases in excise taxes have been
      shown to be effective in reducing smoking among youth. However, the adoption of
      tax increases in any jurisdiction is susceptible to many challenges. Furthermore,
      smuggling of tobacco products and sales of tobacco products over the Internet
      threaten the effectiveness of tobacco tax increases. This article discusses the
      effectiveness of excise tax increases on prevention and reduction of smoking. It
      also discusses factors that influence the legislative adoption of such increases.
      Finally, it examines potential threats to the use of tobacco taxes as a
      prevention tool.

PMID- 12508510
TI  - Protecting our vulnerable food supply.
AB  - From farmyard to dinner table, our food supply presents ample opportunity for
      dangerous microorganisms or their products to thrive and infect or intoxicate
      human beings, often with harmful and sometimes fatal results. Traditional
      controls to protect the food supply include, but are not limited to, law and
      regulation. But law and regulation are only enablers, an underpinning. Most
      important to protection of the food supply is organizational leadership and
      commitment at federal, state, and local levels of government to protect the
      public's health. This article provides examples of such leadership in locales as
      diverse as Australia, New Zealand, and Genesee County, Michigan. Even when a
      supportive law is in place and the will and resources to make the law work exist,
      competing political and economic world-views are constantly at work to amend the
      law and thus adversely affect the public's health.

PMID- 12508511
TI  - New approaches to safe drinking water.
AB  - Up to half the population of some states in the United States drink water from
      small systems not regulated by the Safe Drinking Water Act. The quality of the
      drinking water from these systems is generally unknown and may be suspect. In
      many jurisdictions, private wells are the primary source of water. In some
      instances, construction of wells may have met regulatory requirements but may not
      have adequately prevented disease transmission. Anecdotal information, periodic
      water-borne outbreaks, and recent well surveys suggest that there are public
      health concerns associated with these and similar systems. This article provides
      an assessment of the need for governmental oversight (regulatory and non
      regulatory) of drinking water supplies, describes how a "systems-based" approach
      might be used to evaluate water supply systems and to identify and prevent
      possible contamination, and presents case studies describing the systems-based
      approach as well as a comprehensive approach to environmental health that
      includes drinking water regulation.

PMID- 12508512
TI  - Asthma: the impact of policies on breathing easier.
AB  - Asthma's impact on health, quality of life, and the economy is substantial, and
      asthma rates are increasing. Currently, there is no way to prevent the initial
      onset of asthma, and there is no cure. However, people who have asthma can and do
      lead high quality, productive lives if they control their asthma by taking
      medication and, as appropriate, avoid contact with environmental "triggers."
      These environmental triggers include cockroaches, dust mites, furry pets, mold,
      tobacco smoke, and certain chemicals. This article provides an overview of the
      asthma epidemic in the United States and its impact on communities. It also
      discusses federal, state, and local obstacles and approaches to asthma control
      and provides examples of recent state legislation related to asthma and the key
      factors in their enactment.

PMID- 12508513
TI  - Fluoridation at fifty: what have we learned?
AB  - The question posed by the title of this article encompasses more than just the
      law and science applied to fluoridation. A review of the history and present
      status of fluoridation policy development and implementation makes it quickly
      apparent that the lessons learned are applicable to a wide range of public health
      policy and that the public health community needs to be very concerned about the
      status and trends of legal precedent. Indeed, in the context of recent U. S.
      Supreme Court decisions, the need for a comprehensive and coordinated effort to
      educate the public, legislators, and jurists about the safety and efficacy of
      community water fluoridation is clear. Two fundamental issues are at the core of
      this article: (1) the use of science in formulating and defending public health
      policy, and (2) how to connect scientific fact with the legal process in
      connection with the actual circumstances regarding a community's health status.
      The opening section of this article presents an analysis of fluoridation's great
      success in preventing dental caries over the past 50 years, along with a
      discussion of current data scientifically demonstrating that fluoride is safe
      when properly utilized. A second section provides an overview of one state's
      legislative experience in mandating fluoridation and the political challenges
      encountered. A final section discusses the legal issues associated with
      fluoridation, including the bases of legal challenges to public laws mandating
      it.

PMID- 12508514
TI  - Childhood immunization: laws that work.
AB  - In the United States, many vaccine-preventable disease rates are at an all-time
      low. Low disease rates have been achieved through high rates of immunization
      coverage. Vaccination requirements for school and child care attendance have been
      recommended by the independent Task Force on Community Preventive Services based
      on systematic review of immunization interventions. These requirements have been
      determined to be effective in reducing vaccine-preventable disease and improving
      immunization coverage rates in all at-risk populations. At the same time,
      complacency, increasing vaccine costs, vaccine shortages, and the potential risks
      associated with vaccinations pose challenges to immunization requirements. Some
      states offer not only medical and religious exemptions to immunization
      requirements, but also philosophical exemptions for parents who choose not to
      immunize their children. Policy makers must balance the need to provide
      individual choice with the need to protect children's health.

PMID- 12508515
TI  - Immunization for seniors.
AB  - Vaccine-preventable diseases remain a significant health problem for adults in
      the United States. Far more adults die from the complications of vaccine
      preventable diseases than do children in this country. Available vaccines that
      are effective in preventing morbidity and mortality from these conditions are
      underutilized, and significant racial and ethnic disparities in rates of
      utilization of adult vaccines persist. A variety of important vaccine-preventable
      diseases affect seniors. However, influenza and pneumococcal infections stand out
      as being responsible for more cases and more deaths each year among seniors than
      all other vaccine-preventable diseases in the United States combined. Current
      vaccination rates for these two diseases are far short of the Healthy People 2010
      target rates of 90% immunization of the population of adults aged 65 years or
      over. Despite state efforts to improve vaccination rates of seniors, efforts that
      have included regulatory and educational approaches, significant challenges
      remain in designing immunization programs for seniors that are universally
      effective.

PMID- 12508516
TI  - The legal context of mosquito control for West Nile Virus in New York City.
AB  - When New York City became the first area in the United States to experience an
      outbreak of West Nile Virus, the New York City Department of Health and Mental
      Hygiene assumed responsibility for responding to the threat. That department's
      actions in spraying and taking other actions to control the mosquitoes that
      spread the disease to humans encountered significant opposition from various
      environmental groups. Moreover, complying with existing law that governed
      mosquito control activities became a challenge. This article provides an overview
      of the department's experience in responding to the threat posed by West Nile
      Virus. That experience reinforces the importance of a public health
      organization's collaborating with public health lawyers to produce a better
      public health outcome.

PMID- 12508517
TI  - The impact of laws on HIV and STD prevention.
AB  - HIV and sexually transmitted diseases (STDs) are major public health problems in
      the United States. Since the start of the epidemic, nearly 800,000 persons have
      been reported with AIDS, and approximately 900,000 Americans are currently living
      with HIV infection. Each year, 15 million people in the United States become
      infected with one or more STDs. The direct and indirect costs of the major STDs-
      not including HIV infection--and their complications are estimated to total at
      least $10 billion annually. This article underscores the importance of law and
      other structural factors in the prevention and treatment of HIV and STDs. It
      describes state-level laws on STD screening, name-based reporting of STDs, name
      based reporting of HIV and HIV partner notification implementation, and the
      impact of laws on STD and HIV risk behaviors and prevention services. More
      broadly, the article focuses on how the law influences the vulnerability or
      resilience of persons facing the risk of STDs, HIV infection, or AIDS.

PMID- 12508518
TI  - Graduated licensing for teens: why everybody's doing it.
AB  - While the United States traditionally has allowed quick and easy paths to full
      privilege licensure of drivers at an early age, graduated licensing is becoming
      increasingly popular. The graduated licensing system phases in unrestricted
      driving by allowing beginners to get their initial behind-the-wheel experiences
      under conditions that reduce the risk of collision. As of June 2002, 35 states
      and the District of Columbia had enacted some sort of graduated licensing law.
      Recent evaluations of graduated licensing systems in four states have found
      reductions in crashes among 16-year-old drivers ranging from 11 to 33 percent.
      Yet, not all states have such laws, and many of the graduated licensing systems
      in use lack important provisions, such as nighttime driving and passenger
      restrictions. This article reviews the rules, restrictions, and provisions of the
      graduated licensing model; discusses evaluations of graduated licensing systems;
      identifies and analyzes variations in graduated licensing approaches across
      states; assesses the successes and failures of early graduated licensing laws,
      using New Mexico as an example; and discusses the potential of these systems to
      prevent injuries.

PMID- 12508519
TI  - Kids in cars: closing gaps in child occupant restraint laws.
AB  - This article provides background on the latest research and findings related to
      child occupant restraint laws; highlights recent and proposed legislation
      mandating child occupant restraints, along with strategies and partnerships
      leading to the adoption of the legislation; and identifies practical steps that
      elected officials and public health practitioners can take to adapt and replicate
      those strategies and policies in their states and communities.

PMID- 12508520
TI  - Violence against women: the state of batterer prevention programs.
AB  - While both men and women can be victims, domestic violence usually consists of
      assaults on women, and most violence against women occurs within an intimate
      relationship. In the past twenty years, numerous state and provincial programs to
      intervene in domestic violence cases have developed. The programs tend to focus
      on treating batterers, although they also offer counseling to domestic violence
      victims. The jury remains out on the effectiveness of these programs. A major
      issue is whether the programs use appropriate standards. After an overview of the
      prevalence and nature of domestic violence, this article provides a discussion of
      those standards--their nature, effectiveness, and limitations. Another section
      discusses use of a batterer intervention program in an urban setting. Yet another
      section explores the implications of intimate partner violence and looks again at
      the effectiveness of batterer treatment within intervention programs. The article
      closes with a look at the way one state addresses domestic violence and treats it
      as a crime. An inescapable conclusion to be drawn from the discussion is that
      violence against women has its roots in cultural assumptions that must undergo
      change if the incidence of that violence is to be reduced.

PMID- 12508521
TI  - Perspectives on legal strategies to prevent workplace violence.
AB  - Workplace violence is a continuing problem in the United States, accounting for
      approximately 1,000 deaths each year and for more than 1.5 million incidents of
      nonfatal injuries. State and federal agencies have published guidelines for
      preventing workplace assaults, but there is a need for a strong research agenda
      to address the effectiveness of intervention strategies. After an overview, this
      article provides a discussion of workplace violence from three perspectives. One
      section discusses the process used in a manufacturing setting to install a
      workplace violence prevention program. A second section provides insight into the
      processes used to fully implement a workplace violence prevention program in a
      health care setting. A final section provides insight to the processes brought to
      bear in one state to mandate prevention of workplace violence in the health care
      setting. There is a critical need to evaluate alternative strategies to address
      workplace violence, to make the findings available to legislative and executive
      branches of government, and to implement effective strategies to counter violence
      in the workplace.

PMID- 12508522
TI  - On the edge of tomorrow: fitting genomics into public health policy.
AB  - The project to map the human genome and the field of genetics in general offer
      unique opportunities for not only clinical medicine, but also for public health
      to address and prevent disease. At the same time, genomics is fraught with
      ethical challenges, not the least of which is how to prevent misuse and abuse of
      genetic information by virtue of the legal powers conferred on public health
      organizations. This article examines the role that public health can perform in
      the 21st Century in using the knowledge gained from the human genome project,
      including how to address the barriers to widespread application. The article also
      examines the challenges facing public health in dealing with the legal and
      ethical issues arising from genomics and in avoiding misapplication. While the
      opportunities that genomics offers public health agencies are unprecedented, so
      too are the challenges, which include the fact that genomics exists within a
      legal and policy paradigm that is the opposite of the one in which public health
      has traditionally existed. The danger of abuse and misuse, therefore, is very
      real.

PMID- 12508523
TI  - Will biomonitoring change how we regulate toxic chemicals?
AB  - Biomonitoring is the assessment of human exposure to environmental chemicals by
      measuring the chemicals or their metabolites in human specimens such as blood,
      urine, saliva, or tissue. It has become a powerful public health tool. This
      article discusses the practical application of biomonitoring to address a public
      health problem in a state, to explain how biomonitoring differs from predicting
      exposure through environmental monitoring, to describe the influence
      biomonitoring has had on promulgating regulations aimed at protecting public
      health, and to discuss the position biomonitoring holds in the legal landscape as
      well as its promise in forging laws that will regulate toxic chemicals more
      effectively.

PMID- 12508524
TI  - Preparedness on the frontline: what's law got to do with it?
AB  - The article provides an overview of current work toward identifying core
      competencies for public health emergency and bio-terrorism response, including
      law-related competencies. It demonstrates how competency sets are interrelated
      and how they provide a framework for developing preparedness training for public
      health leaders, public health and health care professionals, law enforcement,
      public health attorneys, and others. The health and safety of America's
      communities hinge on the nation's public health workforce--the estimated 448,254
      public health professionals and 3 million related workforce professionals who
      form the expanded public health system that protects us during times of national
      crisis and in our daily lives. The response capacity of our health agencies and
      communities and their ability to respond effectively will be unpredictable
      without adequate training. Education in the core competencies in emergency
      preparedness and bio-terrorism response is essential. Preparedness at the front
      line means that public health leaders and administrators must be able to
      communicate information, roles, capacities, and legal authorities to all
      emergency response partners during planning, drills, and actual emergencies. Each
      public health worker must be able to describe his or her communication role in
      emergency response within the agency, with the media, and with the general
      public. Law enforcement and state government representatives must understand the
      legal powers of their agencies and of public health agencies for coordinated
      response, mitigation, and recovery efforts in a public health emergency event.

PMID- 12508525
TI  - Immigrant health: legal tools/legal barriers.
AB  - The United States is a country of immigrants, our government having been formed
      by recent arrivals. This trend has continued throughout our history; according to
      the Center for Immigration Studies, more than 26 million immigrants have settled
      in the United States since 1970, and approximately one million new immigrants
      come to the United States each year. The immigrant population faces highly
      diverse health issues that states, cities, and counties must address, many of
      which pose significant legal and policy issues. Social, cultural, and linguistic
      factors complicate those challenges, as does the overlay of federal immigration
      and health policy. Two federal laws, the Welfare Reform Act of 1996 and Title VI
      of the federal Civil Rights Act of 1964, have affected immigrants in two very
      different ways. The former made it difficult for immigrants to qualify for
      publicly funded benefits. In contrast, Title VI made it easier for immigrants to
      obtain benefits by requiring federally funded service providers to offer
      translating services to persons with limited English language skills.
      Tuberculosis treatment is perhaps the most pressing health need among recent
      arrivals to the United States. Methods to slow down and hopefully eliminate this
      disease are underway, but a more comprehensive approach to not only tuberculosis
      but to immigrant health in general is needed. Indeed, it will benefit those
      directly affected by tuberculosis and will have serious implications for the
      entire population for generations to come.

PMID- 12508526
TI  - The dimensions of public health law research.
AB  - Applied public health law research is an essential element for improving the
      legal foundation of public health practice. This article focuses on the proper
      scope and the methodology related to conducting public health law research. In
      addition to considering the issue of translating research into practice, the
      article provides overviews of three current public health law research projects
      and the lessons they provide for researchers.

PMID- 12508527
TI  - The future of public health preparedness.
AB  - This redacted version of a speech by former United States Senator Sam Nunn,
      Chairman of the Nuclear Threat Initiative, points out that although there are
      concerns about global issues involving security and weapons of mass destruction
      and bioterrorism, it was not until September 11, 2001, that these issues (and
      new, unforeseen ones) were getting the funding and attention they deserved. In
      the event of a biological attack, millions of lives may depend on how quickly we
      diagnose the effects, report the findings, disseminate information to the
      healthcare communities and to state and local governments, and bring forth a fast
      and an effective response at the local, state, and federal levels. Public health
      must become an indispensable pillar of our national security framework. As we
      develop a national strategy to respond to these challenges, we must think in the
      broader context of causes as well as symptoms. To provide context for the next 25
      years, Senator Nunn provided an overview of the "Seven Revolutions" for change
      identified by the Center for Strategic and International Studies (CSIS) with
      which he is also associated. Finally, he discusses major security challenges
      facing the United States.

PMID- 12508528
TI  - Conference synopsis and observations.
AB  - The articles reflecting the proceedings of the first-ever national public health
      law conference, Law and the Public's Health in the 21st Century, make it clear
      that public health law is the synergistic intersection of public health practices
      and the law. This article offers, and reflects on, observations organized around
      five themes expressed at that conference about the present status of public
      health law. The first is that public health law is indeed in a renaissance, or
      period of renewal, as evidenced by the rich history of the discipline and the
      growing body of scholarship. Secondly, legal preparedness, which offers a
      framework for action, is a critical component of public health preparedness.
      Third, law can be practiced preventively to positively impact the public's
      health, but unguided application of the law as a tool is problematic. Fourth,
      partnerships between public health and the law and among the professionals in the
      disciplines that touch law and public health are essential to protecting the
      public's health. Finally, public health law is in an era of extraordinary
      challenge, but with those challenges comes great opportunity that must be
      realized if we are to have excellence in public health practice in the 21st
      century.

PMID- 12508529
TI  - Optimal mutation rates in dynamic environments.
AB  - In this paper, we study the evolution of the mutation rate for simple organisms
      in dynamic environments. A model based on explicit population dynamics at the
      gene sequence level, with multiple fitness coding loci tracking a moving fitness
      peak in a random fitness background, is developed and an analytical expression
      for the optimal mutation rate is derived. The optimal mutation rate per genome is
      approximately independent of genome length, something that has been observed in
      nature. Furthermore, the optimal mutation rate is a function of the absolute, not
      relative, replication rate of the superior gene sequences. Simulations confirm
      the theoretical predictions.

PMID- 12508530
TI  - The adaptiveness of defence strategies against cuckoo parasitism.
AB  - Host bird species of the Eurasian Cuckoo, Cuculus canorus, often display egg
      discrimination behaviour but chick-rejection behaviour has never been reported.
      In this paper, we analyse a host-cuckoo association in which both population
      dynamics and evolutionary dynamics are explored in a discrete-time model. We
      introduce four host types, each with their own defence behaviour, displaying
      either egg or chick rejection, neither or both, We also introduce fitness
      functions for each of these host types. Although we can characterize the long
      term behaviour in many cases by a simple heuristic argument which is in
      accordance with common views in ecology, there are a number of other phenomena
      that are not explained within this framework: we describe stable oscillatory
      behaviour and coexistence of two defensive host types. We analyse the scenarios
      in which chick rejection may establish itself and give a first explanation as to
      why this defence trait has never been recorded in nature. We find that chick
      rejectors generally are at an intrinsic disadvantage with respect to a host type
      that rejects eggs. Hosts benefit more from rejecting cuckoo eggs than cuckoo
      chicks, and our model suggests that this is chiefly responsible for the absence
      of chick rejection. Moreover, even though it seems that chick rejection must be
      useful as an extra defence, it is shown that hosts with both defence strategies
      are less likely to establish themselves in competition with egg-rejectors than
      hosts which reject chicks only. These results provide insight in the extent to
      which adaptations may be perfected by natural selection.

PMID- 12508531
TI  - On the cable theory of nerve conduction.
AB  - Conduction of an impulse in the nonmyelinated nerve fiber is treated
      quantitatively by considering it as a direct consequence of the coexistence of
      two structurally distinct regions, resting and active, in the fiber. The profile
      of the electrical potential change induced in the vicinity of the boundary
      between the two regions is analyzed by using the cable equations. Simple
      mathematical formulae relating the conduction velocity to the electrical
      parameters of the fiber are derived from the symmetry of the potential profile at
      the boundary. The factors that determine the conduction velocity in the
      myelinated nerve fiber are reexamined.

PMID- 12508532
TI  - A mathematical model of human atrioventricular nodal function incorporating
      concealed conduction.
AB  - This work develops a mathematical model for the atrioventricular (AV) node in the
      human heart, based on recordings of electrical activity in the atria (the upper
      chambers of the heart) and the ventricles (the lower chambers of the heart).
      Intracardiac recordings of the atrial and ventricular activities were recorded
      from one patient with atrial flutter and one with atrial fibrillation. During
      these arrhythmias, not all beats in the atria are conducted to the ventricles.
      Some are blocked (concealed). However, the blocked beats can affect the
      properties of the AV node. The activation times of the atrial events were
      regarded as inputs to a mathematical model of conduction in the AV node,
      including a representation of AV nodal concealment. The model output was compared
      to the recorded ventricular response to search for and identify the best possible
      parameter combinations of the model. Good agreement between the distribution of
      interbeat intervals in the model and data for durations of 5 min was achieved. A
      model of AV nodal behavior during atrial flutter and atrial fibrillation could
      potentially help to understand the relative roles of atrial input activity and
      intrinsic AV nodal properties in determining the ventricular response.

PMID- 12508533
TI  - Empathy leads to fairness.
AB  - In the Ultimatum Game, two players are asked to split a prize. The first player,
      the proposer, makes an offer of how to split the prize. The second player, the
      responder, either accepts the offer, in which case the prize is split as agreed,
      or rejects it, in which case neither player receives anything. The rational
      strategy suggested by classical game theory is for the proposer to offer the
      smallest possible positive share and for the responder to accept. Humans do not
      play this way, however, and instead tend to offer 50% of the prize and to reject
      offers below 20%. Here we study the Ultimatum Game in an evolutionary context and
      show that empathy can lead to the evolution of fairness. Empathy means that
      individuals make offers which they themselves would be prepared to accept.

PMID- 12508534
TI  - Photoreceptor death: spatiotemporal patterns arising from one-hit death kinetics
      and a diffusible cell death factor.
AB  - Retinitis pigmentosa (RP) is an inherited disease affecting approximately 1:4000
      individuals in North America. It is characterized clinically by the gradual
      apoptotic death of photoreceptor cells that occurs nonuniformly across the
      surface of the retina. Recently, it has been demonstrated that the time of death
      of many individual photoreceptors is random, a fact that must be reconciled with
      the spatiotemporal patterns of photoreceptor degeneration that are observed in
      patients with RP. One possible explanation is that a diffusible toxic factor is
      released by dying photoreceptors and induces adjacent cells to likewise undergo
      apoptosis. To determine if such a mechanism can result in patchy distributions of
      photoreceptor death, as frequently observed in RP patients, we studied cell
      attrition produced by a bistable biochemical switch in an idealized one
      dimensional retina. We found that with a reasonable choice of parameter values,
      our model was able to produce patterns of cell death resembling those observed in
      RP. In the context of this model, patches on the order of histologically
      observable size could develop from a single release event, but their rates of
      formation were independent of the concentration of toxic factor released.
      Instead, factor concentration affected the overall rate of cell death, the number
      of degenerating patches, and their distribution across the retina.

PMID- 12508535
TI  - [Apoptosis of human lung carcinoma cell line GLC-82 induced by high power
      electromagnetic pulse].
AB  - BACKGROUND & OBJECTIVE: Electromagnetic pulse (EMP) could be used for
      sterilization of food and the efficiency is higher than 2450 MHz continuous
      microwave done. This study was designed to evaluate the effect of electromagnetic
      pulse (EMP) on apoptosis of human lung carcinoma cell line GLC-82, so that to
      explore and develop therapeutic means for cancer. METHODS: The injury changes in
      GLC-82 cells after irradiated with EMP (electric field intensity was 60 kV/m, 5
      pulses/2 min) were analyzed by cytometry, MTT chronometry, and flow cytometry.
      The immunohistochemical SP staining was used to determine the expressions of bcl
      2 protein and p53 protein. The stained positive cells were analyzed by CMIAS-II
      image analysis system at a magnification 400. All data were analyzed by SPSS8.0
      software. RESULTS: EMP could obviously inhibited proliferation and activity of
      lung carcinoma cell line GLC-82. The absorbance value (A570) of MTT decreased
      immediately, at 0 h, 1 h, and 6 h after the GLC-82 cells irradiated by EMP as
      compared with control group. The highest apoptosis rate was found to reach 13.38%
      by flow cytometry at 6 h after EMP irradiation. Down-regulation of bcl-2
      expression and up-regulation of p53 expression were induced by EMP. CONCLUSION:
      EMP promotes apoptosis of GLC-82 cells. At same time, EMP can down-regulate bcl-2
      expression and up-regulate p53 expression in GLC-82 cells. The bcl-2 and the p53
      protein may involve the apoptotic process.

PMID- 12508536
TI  - [Apoptosis of K562 cells induced by antisense-oligonucleotides of CRKL gene].
AB  - BACKGROUND & OBJECTIVE: It was recently reported that the proteins coded by CRKL
      (CT10 regulator of kinase like, CRK like) gene play an important role in the
      pathogenesis of chronic myeloid leukemia (CML). This study was designed to
      investigate the effect of antisense oligonucleotides of CRKL gene (CRKL-ASDON) on
      CML K562 cell lines. METHODS: K562 cells were transfected with CRKL-ASDON, using
      liposome as the vector. The changes of cell morphology, cell cycle, and gene
      expression were observed through living cell count, transmission electron
      microscopy, flow cytometry (FCM), DNA Ladder assay. RESULTS: Under the action of
      CRKL-ASDON, growth of K562 cell was markedly inhibited. An apoptotic peak
      appeared before diploid peak in FCM; various apoptotic stages of K562 cells were
      observed under electron microscope; over ladder-shaped band of cell apoptosis was
      seen in abstracted DNA of the gene group by gel electrophoresis. Meanwhile, the
      above changes did not appear in the control. CONCLUSION: CRKL gene is an
      important factor in the pathogenesis of Ph-positive CML.

PMID- 12508537
TI  - [MnSOD gene regulated by aminopeptidase N promoter specifically protects bone
      marrow from radiation].
AB  - BACKGROUND & OBJECTIVE: It is an effective way to induce radio-tolerant gene into
      hematopoietic cells in bone marrow for overcoming the suppression of radiotherapy
      on hematopoietic system. However, this also increases the radiation tolerance of
      tumor cells. This study was designed to investigate a method to specifically
      protect bone marrow cell from being damaged by radiation, along without
      increasing resistance of tumor cell to radiation. METHODS: The retrovirus vector
      of manganese superoxide dismutase (MnSOD) gene regulated by aminopeptidase N
      (APN) bone marrow-specific gene promoter was constructed and induced into
      myeloblastic KG1a and cancer cell BEL7402. MnSOD mRNA level was analyzed by PT
      PCR; MnSOD activity in the cells was determined; the sensitivity of bone marrow
      cell and hepatic carcinoma cell to x-ray was detected by cell survival test; the
      cell apoptosis was analyzed with flow cytometry and fractural DNA
      electrophoresis. RESULTS: The MnSOD mRNA level and enzyme activity in KG1a cells
      transferred with the gene was obviously increased. Expression of MnSOD mRNA drove
      by APN myelo-specific promoter effectively inhibited apoptosis of KG1a cells
      induced by radiation and endowed KG1a cell line with the enhancement of tolerance
      to radiation, which increased by 3.7 folds compared to parental cells at the dose
      of 10 Gy. In contrast, the level of MnSOD mRNA, the enyme activity of MnSOD and
      the radiosensitivity had no significant change in BEL 7402 cells transduced with
      MnSOD gene. CONCLUSION: APN bone marrow-specific promoter could control MnSOD
      gene expression highly in myeloid cell and lower in cancer cell. In the process
      of killing of cancer cell by x-ray, MnSOD gene regulated by APN bone marrow
      specific promoter could specifically protect myeloid cell. This study provides a
      new clue to solve the bone marrow suppression in high dose radiotherapy.

PMID- 12508538
TI  - [Malignant transformation of human bronchial epithelial cell (BEAS-2B) induced by
      depleted uranium].
AB  - BACKGROUND & OBJECTIVE: It is clear from works already reported that depleted
      uranium (DU) affect human health. However, the late effect, especially the
      carcinogenesis, was not clearly understood. This study was designed to
      investigate the malignant transformation of human bronchial epithelial cell
      induced by insoluble DU and lung cancer related gene expression pattern, through
      imitating the condition that human absorbs depleted uranium aerosol. METHODS:
      Adenovirus-12/SV40 virus immortalized human bronchial epithelial cells (BEAS-2B)
      were reacted with insoluble DU oxide (dUO2); the characteristics of malignant
      transformation of cells were identified through observing the multiplication time
      of different generation cells, serum resistance, colony formation rate of semi
      solid agar, and tumorigenesis in nude mice. Gene expression pattern of
      transferred BEAS-2B cell induced by DU was determined using 213 lung cancer
      related gene arrays. RESULTS: The multiplication time of BEAS-2B cell treated
      with DU was obviously decreased and the serum reistance was significantly
      increased in 5th generation; the anchorage independent growth (semi-solid agar
      colony formation) was appeared in 10th generation cell. The 15th generation cell
      formed tumor in nude mice. DMSO showed overt protection effect on malignant
      transformation of BEAS-2B cell. The analyzing results of 213 lung cancer related
      gene arrays showed that the expression level changed in more than 70 genes of
      transferred cells, including the overt decrease of level of gene expression in
      more than 10 genes. CONCLUSION: DU has carcinogenesis in vitro.

PMID- 12508539
TI  - [Monitoring impact of measurement of urinary beta-human chorionic gonadotropin on
      orthotopic implantation model of human ovarian carcinoma in athymic nude mice].
AB  - BACKGROUND & OBJECTIVES: Tumor orthotopic transplantation model has become the
      main carrier for tumor animal experiment. However, there was no convenient and
      reliable method to monitor tumor growth in animal body. This study was designed
      to evaluate the monitoring impact of urinary beta-human chorionic gonadotropin
      (beta-HCG) on tumor growth in orthotopic implantation model. METHODS: Pclone-beta
      HCG stably transfected human ovarian carcinoma cell line A2780-CG was made as the
      orthotopic implantation model. The urinary beta-HCG/creatine ratio was
      continuously determined and plotted into curve, so as to indirectly know the rule
      of tumor growth in nude mice and the monitoring value of the ratio for
      intraperitoneal chemotherapy by cisplatin. RESULTS: The tumorigenesis time in
      beta-HCG system transfected tumor cell A2780-CG was similar to that in the
      original cell line. The content of urinary beta-HCG/creatine had a positive
      correlation to tumor weight in animal body (r = 0.98); After chemotherapy with
      cisplatin, the beta-HCG/creatine ratio showed progressively decreased.
      CONCLUSION: beta-HCG system could be used to sensitively and non-invasively
      monitor the tumor growth in orthotopic implantation model of human ovarian
      carcinoma in nude mice. Meanwhile, it provides a new convenient monitoring method
      for tumor treatment in the model.

PMID- 12508540
TI  - [Effect of interventional chemothermotherapy on vascular permeability of tumor
      liver tissue and normal liver tissue in VX-2 tumor-bearing rabbits].
AB  - BACKGROUND & OBJECTIVE: It was reported that heating could enhance the
      sensitivity of chemotherapy with Adriamycin and increase the intracellular
      content of Adriamycin. The aim of this study was to investigate the effect of
      interventional chemothermotherapy on vascular permeability of tumor liver tissue
      and normal liver tissue in VX-2 tumor-bearing rabbits. METHODS: Thirty rabbits
      used as implanted hepatocarcinoma model were randomly divided into 3 groups: non
      perfusion group (injected only with 1% Evans blue after catheterization),
      normothermic perfusion group (the perfusion fluid was 25 degrees C normal
      solution), and hyperthermic perfusion group(the perfusion fluid was 60 degrees C
      normal solution). The contents of Evans blue in the tissues of three groups,
      which were used as the indices of vascular permeability, were calculated by the
      standard curve and spectrophotometry. RESULTS: The Evans blue contents in tumor
      liver tissue and normal liver tissue is statistically different (P < 0.05). There
      was no over difference of the Evans blue contents in two kinds of tissue between
      normal perfusion group and non-perfusion group. There was overt difference of the
      Evans blue contents in two kinds of tissue between hyperthermic perfusion group
      and normothermic perfusion group. CONCLUSION: Interventional chemothermotherapy
      could increase the vascular permeability of normal liver tissue and tumor liver
      tissue.

PMID- 12508541
TI  - [Prokaryotic expression of endostatin and preparation of polyclonal antibody].
AB  - BACKGROUND & OBJECTIVE: The aim of this study was to express and purify human
      endostatin and to prepare polyclonal antibody of mouse anti-human endostatin.
      METHODS: The cDNA of endostatin was amplified by PCR, then recombined into
      prokaryotic expression vector and transformed into Escherichia coli BL21 for
      expression; the mice were immunized with purified products. RESULTS: Prokaryotic
      expression vector pQE-30 of human endostatin was successfully constructed; the
      expression product was gained after pQE-30 was transferred into BL21. After
      purified by Ni affinity chromatography, the product was identified to be a single
      component by SDS-PAGE. Western blot analysis showed that high titer mouse anti
      human endostatin polyclonal antibody was successfully prepared. CONCLUSION:
      Highly purified expression product and prepared polyclonal antibody provide the
      necessary material for further study.

PMID- 12508542
TI  - [Expression of inducible nitric oxide synthase and basic fibroblast growth factor
      in supraglottic squamous cell carcinoma and their clinical significance].
AB  - BACKGROUND & OBJECTIVE: To the authors' knowledge, the relationship between
      inducible nitric oxide synthase (iNOS) and basic fibroblast growth factor (bFGF)
      and cervical lymph node metastasis of supraglottic squamous cell carcinoma
      (SGSCC) has not been addressed to date. This study was designed to investigate
      the effect of iNOS and bFGF on biological behavior of cervical lymph node
      metastasis in SGSCC. METHODS: The authors conducted a contrast analysis for 64
      patients with SGSCC (experimental group) and 33 patients with chronic laryngeal
      mucositis (control group). Pathologic imaging analysis was used for quantitative
      determination. RESULTS: 1. Positive staining site of iNOS and bFGF was
      concentrated in cytoplasm; bFGF was also expressed in nuclei and intracellular
      substance. 2. The expressions of iNOS and bFGF were significantly higher in
      experimental group than in control group. 3. The expression in cervical lymph
      node positive group was significantly higher than that in negative group.
      However, there was no statistical significance between primary negative-follow
      positive group and primary positive group. CONCLUSION: The expression of iNOS and
      bFGF was closely associated with SGSCC, and can be considered to be a predictor
      for lymph node metastasis of SGSCC.

PMID- 12508543
TI  - [Relationship between lymph node metastasis and the expressions of E-cadherin, N
      cadherin, and matrix metalloproteinase in breast carcinoma].
AB  - BACKGROUND & OBJECTIVE: There is little ideal predictor available on evaluating
      the lymph node metastatic potential of breast carcinoma. This study was designed
      to determine the expression of gene products of E-cadherin (epithelial), N
      cadherin (nerve), and matrix metalloproteinase-9 (MMP-9) in breast carcinoma
      tissue and investigate their association with the invasion and metastasis of
      breast carcinoma. METHODS: The authors examined the expressions of E-cadherin, N
      cadherin, and MMP-9 in 72 cases of breast carcinoma(39 cases with lymph node
      metastasis and 33 cases without lymph node metastasis) by immunohistochemistry.
      Multivariable Cox proportional hazards model was used to analyze the patients'
      prognosis. RESULTS: The average ranks of E-cadherin in lymph node metastasis
      group and no lymph node metastasis group were 29.19 and 45.14, respectively, with
      significant difference (P < 0.001). The expression of E-cadherin was correlated
      inversely with the metastasis of breast carcinoma. The average ranks of N
      cadherin and MMP-9 were 40.04 and 42.97 in lymph node metastasis group, and 32.32
      and 28.85 in no lymph node metastasis group, both with significant difference (P
      < 0.05), and these expressions were positively correlated with the lymph node
      metastasis of breast carcinoma. The patients who had high expression of E
      cadherin had a longer survival time. CONCLUSION: Expression of E-cadherin, N
      cadherin, and MMP-9 are associated strongly with lymph node metastasis of breast
      carcinoma. These proteins are indicators of metastasis potential and prognosis of
      breast carcinoma.

PMID- 12508544
TI  - [Relationship between Helicobacter pylori infection and expressions of tumor
      suppressor genes in gastric carcinoma and related lesions].
AB  - BACKGROUND & OBJECTIVE: Helicobacter pylori (Hp) are believed to be a carcinogen
      of gastric carcinoma. However, its mechanism was yet not clearly understood. p53,
      p21WAF1, and p16 are main negative regulator genes of cell cycle. This study was
      designed to investigate the relationship between these 3 genes and Hp infection.
      METHODS: The authors examined the expression of these 3 tumor suppressor genes
      and Hp infection in 65 cases with chronic atrophic gastritis (CAG), 93 cases with
      intestinal metaplasia(IM), 94 cases with gastric epithelial dysplasia (GED) and
      60 cases with gastric carcinoma (GC) using HID-AB (pH 2.5)-PAS, SP
      immunohistochemistry staining, and Warthin-Starry staining. RESULTS: For CAC, IM
      stage I-II, IM stage III, GED stage I, GED stage II-III, and GC, the positive
      expression rates of p53 were 0, 1.64%, 6.25%, 5.45%, 23.08%, and 70.00%,
      respectively (increased with pathological process); the positive expression rates
      of p21WAF1 were 100%, 95.08%, 100%, 100%, 71.79%, and 45.00%, respectively; the
      positive expression rates of p16 were 83.08%, 81.97%, 78.13%, 89.09%, 69.23%, and
      40.00%, respectively. All the expression of these 3 genes showed significant
      difference between GED stage II-III and GED stage I, GC and GED stage II-III. In
      the same pathological changes, the positive expression rate of these 3 genes was
      higher in Hp infection group than in no Hp infection group, while there was no
      significant difference (P > 0.05). CONCLUSION: The mutation of p53 and
      inactivation of p21WAF1 and p16 play an important role in carcinogenesis of
      stomach. However, Hp infection was not associated with the abnormal expression of
      these 3 genes.

PMID- 12508545
TI  - [Effect of NF-kappa B pathway on apoptosis of hepatic carcinoma cell line-7721
      induced by TNF-alpha].
AB  - BACKGROUND & OBJECTIVE: It was proved that nuclear factor-kappa B play an
      important role in the activation of immune cell, anti-virus, various stress
      reaction, and regulation of apoptosis, etc. The objective of this study was to
      investigate the effect of NF-kappa B signal-transduction pathway on apoptosis of
      hepatic carcinoma cell line-7721 induced by TNF-alpha. METHODS: The activation of
      TNF-alpha on NF-kappa B conduction pathway was determined with ELISA and
      immunohistochemistry. Then the activation of TNF-alpha was blocked with TPCK.
      Flow cytometry was used to detect apoptosis. RESULTS: 1. TNF-alpha could activate
      the NF-kappa B conduction pathway. 2. TPCK could inhibit the activation of NF
      kappa B induced by TNF-alpha. 3. Inactivation of NF-kappa B by TPCK could enhance
      apoptosis induced by TNF-alpha. CONCLUSION: NF-kappa B conduction pathway of 7721
      cell takes part in anti-apoptosis and plays an important role in the tolerance on
      cytotoxicity of TNF-alpha of 7721 cell. Inhibition of NF-kappa B conduction
      pathway may has potential value in tumor treatment.

PMID- 12508546
TI  - [Rule of lymph node metastasis in the cancer of mouth floor and its treatment].
AB  - BACKGROUND & OBJECTIVE: There was little report on the rule of lymph node
      metastasis in the cancer of mouth floor. The aim of this study was to investigate
      the rule of lymph node metastasis and investigate the reasonable treatment.
      METHODS: A total of 79 cases with squamous carcinoma of mouth floor were included
      into this study retrospectively. The distributive difference of clinical and
      pathological positive lymph node was compared. The recurrent rate of the patients
      who were performed with radical neck dissection and supra-half-neck dissection in
      clinical positive lymph node group were compared with the recurrent rate of the
      patients who were preformed with radical neck dissection, supra-half-neck
      dissection, submandibular triangle dissection, and clinical observational group.
      RESULTS: Clinical and pathological positive lymph node was found mainly in II
      region (61.8% and 40.0%, respectively), secondly in I and/or III region, and
      rarely in IV, V, and VI region. In clinical positive lymph node group, the
      recurrent rate of the patients who performed with radical cervical neck
      dissection was lower than supra-half-neck dissection, but without statistical
      significance (chi 2 = 3.403, P = 0.065). In clinical cervical negative lymph node
      group, the recurrent rates of the patients performed with supra-half-neck,
      submandibular triangle dissection, and in clinical observational group were 11.1%
      (1/9), 40.0% (2/5), and 23.5% (4/17), without statistical significance (chi 2 =
      1.554, P = 0.46). CONCLUSION: Lymph node metastasis of cancer of floor of mouth
      mainly distributes in I, II, III region; The patients with negative cervical
      lymph node should be performed lymph node dissection in I, II, III region (supra
      half-neck).

PMID- 12508547
TI  - [Expression and clinical significance of matrix metalloproteinase-9 and vascular
      endothelial growth factor in oral squamous cell carcinomas].
AB  - BACKGROUND & OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) is closely associated
      with the metastasis and infiltration of tumor. It was recently discovered that it
      is also associated with angiogenesis of tumor. This study was designed to
      investigate the expressions of MMP-9 and vascular endothelial growth factor
      (VEGF) in oral squamous cell carcinoma (OSCC) tissue and their association with
      metastasis and infiltration of OSCC. METHODS: The expressions of MMP-9 and VEGF
      were detected on paraffin-embedded samples from 51 cases of OSCC, 10 cases of
      oral squamous cell papilloma, and 10 of normal oral mucosa by
      immunohistochemistry. RESULTS: MMP-9 and VEGF showed negative or weak positive
      expression in normal oral mucosa and oral squamous cell papilloma. The positive
      expression rate of MMP-9 and VEGF in OSCC were 78.4% (40/50) and 82.4% (42/51);
      the coexpression of MMP-9 and VEGF was 66.7% (34/51). CONCLUSION: There was
      difference between the expression of MMP-9 and VEGF in OSCC tissue. The
      infiltration of tumor cell is closely associated with the expression of MMP-9 (P
      < 0.01). Cervical lymph node metastasis closely correlates to the expression
      level of VEGF (P < 0.01). MMP-9 and VEGF could be used as biological indices for
      clinically evaluating infiltrative and metastatic potential of OSCC.

PMID- 12508548
TI  - [Expression of p53 and vascular endothelial growth factor in esophageal squamous
      cell carcinoma and their clinical significance].
AB  - BACKGROUND & OBJECTIVE: Experimental study proved that the coexpression of p53
      and vascular endothelial growth factor (VEGF) play an important role in
      angiogenesis of tumor. The aim of this study was to investigate the mechanism
      that p53 participate angiogenesis and the relationship between the expression of
      p53 and VEGF and clinical pathologic parameters and prognosis of esophageal
      squamous cell carcinoma (ESCC). METHODS: The expressions of p53 and VEGF in
      operative samples from 76 ESCC patients were detected by immunohistochemistry.
      The vascular endothelial cells in tumor tissue were labeled by F VIII factor
      antibody for counting microvessel density (MVD). RESULTS: The expression rates of
      p53 and VEGF were 60.5% and 56.5%; total expression rate was 42.1%. The
      expression rates of p53 and VEGF were strongly associated with distal metastasis
      and vascular infiltration of ESCC (P < 0.05, P < 0.01). Distal metastasis and
      vascular infiltration usually occurred in the patients whose mutant p53 and VEGF
      were both positive expression. The MVDs in p53(+) or VEGF(+) (31.7 +/- 11.5; 33.8
      +/- 11.7) were both significantly higher than that in p53(-) or VEGF(-) (22.4 +/-
      10.6; 21.2 +/- 9.3, P < 0.05). The MVD reached the maximum in the patients whose
      p53 and VEGF were both positive. CONCLUSION: Mutant p53 expression is closely
      associated with the angiogenesis and distal metastasis of ESCC; Expression of p53
      and VEGF could be used as an important biological indices for evaluating the
      malignant degree of ESCC. Combined determination of p53 and VEGF expression has
      important clinical significance.

PMID- 12508549
TI  - [Influence of preoperative transcatheter arterial chemoembolism on immunity after
      hepatectomy in patients with liver cancer].
AB  - BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolism (TACE) is one of
      important therapeutic method for hapatocarcinoma. Post-operative TACE could
      reduce recurrent rate definitely. However, there were much debate about the
      function and effect of preoperative TACE. This study was conducted to evaluate
      the effect of preoperative TACE on immunity of the patients with recurrent
      hepatocarcinoma who performed combined treatment. METHODS: The patients with
      primary hepatocarcinoma who performed operative TACE were collected. The dynamic
      changes of cellular immunity and humoral immunity in pre-intervention, pre
      operation, combined treatment after recurrence periods were determined by flow
      cytometry and ELISA, and were compared with the data of the recurrent patients
      after simple operation. RESULTS: In TACE group: CD3, CD4, CD56 decreased
      slightly; serum IgM increased slightly, with no significant difference compared
      to pre-intervention (P < 0.05); At the time of combined treatment after
      recurrence, CD8 increased and CD4/CD8 decreased (0.8 +/- 0.3%), the immune
      suppression was slight. In sample operation group, CD3, CD4, CD56 were 49.0 +/-
      9.1%, 19.0 +/- 4.8%, 18.6 +/- 9.9%; the immune suppression was severe. The
      operation significantly decreased the patients' CD3, CD4, and CD19. The
      pathologic results showed that the tumor capsule, intrahepatic daughter foci,
      tumor thrombus, and the radical degree in preoperative group were much better
      than those in simple operation group. CONCLUSION: The preoperative TACE do not
      obviously influence the immunity; furthermore, it can relieve the immune
      depression after operation and is a remedy of the surgical treatment. It is
      important to grasp the indication of preoperative TACE.

PMID- 12508550
TI  - [MRI diagnosis of tumor involving brachial plexus].
AB  - BACKGROUND & OBJECTIVE: The incidence rate of tumor involving brachial plexus was
      rare and its clinical diagnosis is difficult. Several foreign authors have
      reported that magnetic resonance imaging (MRI) is the best imaging diagnosis
      method. Howev, there was little report about this in China. This study was
      designed to investigate the diagnostic value of MRI in tumor involving brachial
      plexus. METHODS: The MRI manifestations in 13 patients with tumor involving
      brachial plexus (including 3 neurofibromatosis, 4 Pancoast's tumor, 6 metastatic
      tumor; 8 confirmed pathologically, 2 confirmed by biopsy, 3 neurofibromatosis
      confirmed clinically) were analyzed retrospectively. RESULTS: In 3 patients with
      neurofibromatosis, 2 cases showed growing along brachial plexus and represented
      spindle-shape; 1 cases showed growing crushing and encircling brachial plexus and
      represented ball-shape. There were middle or poor even signals on T1WI, and overt
      high and high-low mixed signals on T2WI (intense with even or uneven after
      enhancement). All 4 cases of Pancoast's tumor infiltrated brachial plexus. In 6
      cases of metastatic tumor, 5 cases represented that localized bump encircled and
      infiltrated brachial plexus. 1 case represented that the tumor tissue effusively
      infiltrate brachial plexus. No special manifestation was shown on MRI of
      Pancoast's tumor and metastatic tumor. There were the similar or lower signals on
      T1WI, and high signals on T2WI (intense with even or uneven after enhancement).
      CONCLUSION: The coronal position of T1WI could clearly represent the relationship
      between brachial plexus and tumor, the involving extent of brachial plexus.
      Therefore, MRI is a effective imaging method for diagnosis of primary or
      secondary tumor involving brachial plexus.

PMID- 12508551
TI  - [Significance of detecting serum tumor supplied group of factors in differential
      diagnosis of neck masses].
AB  - BACKGROUND & OBJECTIVE: It was reported that serum tumor supplied group of
      factors (TSGF) were useful in differential diagnosis of various benign and
      malignant tumor. However, there was little report involving the differential
      diagnosis of neck masses. This study was designed to evaluate the significance of
      serum TSGF in differential diagnosis of neck masses. METHOD: Serum TSGFs on the
      samples from 128 patients with neck masses were detected by immunohistochemistry.
      Forty seven non-tumor patients served as control. RESULTS: Serum TSGF level and
      positive rate in various malignant group (including nasopharyngeal carcinoma, non
      Hodgkin's disease, and metastatic carcinoma which primary lesion remained
      unknown) were higher than that in benign mass group (including cervical
      lymphoadenitis, or reactive hyperplasia, and neck lymphoid tuberculosis without
      general active tuberculosis), with very significant difference (all P < 0.01).
      There was no significant difference between two benign masses or neck benjgn
      masses or neck benign masses and non tumor patients (all P > 0.05). The
      differential diagnosis parameters of positive serum TSGF for neck malignant
      masses were: sensitivity 78.16%, specificity 75.61%, efficiency 77.34%, positive
      predictive value [PV(+)] 87.18%, negative predictive value [PV(-)] 62.00%.
      CONCLUSION: Determination of serum TSGF was useful in differential diagnosis of
      neck masses.

PMID- 12508552
TI  - [Significance of urinary nuclear matrix protein 22 in diagnosis of transitional
      cell carcinoma of urinary tract].
AB  - BACKGROUND & OBJECTIVE: There is no effective non-invasive monitoring method for
      transitional cell carcinoma of urinary tract(TCCU). It was recently reported that
      nuclear matrix protein 22(NMP22) could be used to diagnose TCCU. This study was
      designed to evaluate the significance of NMP22 in TCCU as a new urinary tumor
      marker and its influence factors. METHODS: The authors detected 87 patients with
      urinary system disease(including 29 cases with TCCU) with ELISA-NMP agent box.
      The patients with urinary infection were excluded. RESULTS: The positive value
      was set at more than 10 u/ml. The sensitivity and specificity of NMP22 on TCCU
      were 86.2% and 94.3%, respectively (benign diseases of urinary system used as
      control), with significant advantages over voided-urine cytology (86.2% vs 42.3%,
      P < 0.001). The main factors that caused false-positive results were urinary
      infection, the other malignant tumors of urinary system, bowel interposition, and
      nephrolith. CONCLUSION: Urinary NMP22 is a good tumor marker and could be used an
      alternation of voided-urine cytology for monitoring and diagnosis of TCCU.

PMID- 12508553
TI  - [Influence of induction chemotherapy on long-time effect of patients with tongue
      squamous cell carcinoma].
AB  - BACKGROUND & OBJECTIVE: Induction chemotherapy is important in comprehensive care
      of patients with oral tongue squamous cell carcinoma. However, the effect of
      induction chemotherapy on the long-time effect was not clearly known. This study
      was designed to investigate the relationship between pathological negativity of
      primary lesion after induction chemotherapy and long-time effect in tongue
      squamous cell carcinoma. METHODS: The 3 year survival rate, the 5 year survival
      rate, survival rate with tumor free, and reasons of treatment failure of 25
      patients with tongue squamous cell carcinoma which primary lesion was
      pathologically negative were analyzed retrospectively. RESULTS: The 3 year
      survival rate and the 5 year survival rate of the patients which primary lesion
      (91.75% and 91.66%) was pathologically negative were both higher than the
      patients with residual tumor (64.52% and 57.0%). The survival rate with tumor
      free in the former was also higher than that in the latter. The main reasons for
      treatment failure were local recurrence and/or regional lymph node
      metastasis/recurrence. CONCLUSION: Induction chemotherapy could increase the long
      time survival rate of the patients with tongue squamous cell carcinoma whose
      primary lesion was pathologically negative.

PMID- 12508554
TI  - [Application of microdissection combined with RNA linear amplification].
AB  - BACKGROUND & OBJECTIVE: Microdissection has become indispensable for the
      selective analysis of stroma-free tumor cell. However, To obtain sufficient RNA
      from microdissected cells is difficult. The study was designed to seek a specific
      way to separate nasopharyngeal carcinoma (NPC) cells from stromal cells and to
      amplify the RNA from microdissected NPC cells. METHODS: NPC cells were obtained
      using microdissection from frozen NPC tissue sections, then RNA was extracted
      from the microdissected NPC cells and reverse transcribed in vitro. The
      expression levels of beta-actin and GADPH in amplified RNA were detected using RT
      PCR. RESULTS: About 20,000-40,000 NPC cells were obtained, RNA was extracted from
      the cells, about 0.5-2.5 kb RNA fragments were obtained after RNA linear
      amplification and beta-actin and GADPH levels were integral. CONCLUSION:
      Microdissection combined with RNA linear amplification can be used to
      successfully obtain pure NPC cells, the integrity of amplified RNA is good and
      can be used in further research.

PMID- 12508555
TI  - [Matrix metalloproteinases and breast cancer].
AB  - Matrix metalloproteinases(MMPs) are a family of zinc-dependent proteinases
      involved in the degradation of the extracellular matrix. A great deal of studies
      showed that they have the important role in invasiveness and metastasis of breast
      carcinoma. It was recently reported that they also contribute to the genesis and
      development of primary breast carcinoma. MMPs take part in these processes on
      various mechanisms. Clinically, MMPs showed values for treatment and judging
      prognosis of breast carcinoma. At present, the scholars are investigating the
      mechanisms of MMPs on breast carcinoma by various methods, so as to approach a
      new pathway for treating breast carcinoma.

PMID- 12508556
TI  - [Research on breast cancer susceptibility genes].
AB  - With the increasing of the incidence rate of breast carcinoma year after year,
      the susceptibility genes of breast carcinoma was paid more and more attention.
      The study on susceptibility genes play an important role in early diagnosis and
      prevention for the individuals with family history of breast carcinoma,
      elucidation of pathologic mechanism of sporadic breast carcinoma, early diagnosis
      and adjudging prognosis, research on drug sensitivity, differential diagnosis of
      benign and malignant disease, etc. There were many studies on the high-penetrance
      susceptibility genes (BRCA1, BRCA2). However, some low-penetrance susceptibility
      gene, for example, the members of hormone metabolism related enzymes genes CYP
      family (CYP17, CYP19, CYP1A1, etc.), the carcinogen metabolism related gene
      (GSTM1, NAT1, NAT2), and DNA damage repair gene (ATM) were not clearly
      understood. The aim of this study was to review the present research situation of
      common susceptibility genes of breast carcinoma found already.

PMID- 12508557
TI  - Cell migration and evolutionary significance of GnRH subtypes.
AB  - Hypothetically it can be assumed that in advanced teleost fishes, GnRH-III and
      GnRH-IV neurons migrate along the 'telencephalonic' (anterior) and
      'diencephalonic' (posterior) migratory route, which perhaps fuses in primitive
      teleost fishes and land vertebrates to form the 'ancient migratory route' (in all
      probability = nervus terminalis; see Von Bartheld et al., 1988) of GnRH-I
      neurons. The difference in distribution pattern of GnRH forms in the vertebrate
      brain is due to distinct embryonic origins: (1) Cells of olfactory origin, which
      give rise to GnRH-I (salmon, catfish, chicken I, mammalian GnRH) are distributed
      along the olfactory system and the basal forebrain in primitive fishes and in
      land vertebrates; GnRH-I might be pivotal for LH/FSH synthesis-release, olfaction
      and metamorphosis in lower vertebrates. In advanced teleost fishes, neurons
      synthesizing GnRH-III ('salmon' GnRH) originate from the olfactory system; they
      are distributed along the basal olfactory bulbs, with distinct ganglia (NOR) at
      the caudalmost part of the olfactory bulbs and few scattered cells in the basal
      telencephalon. The NOR might function as a neuromodulator, hypophysiotropic
      hormone and regulate visual associated reproductive behaviors. (2) Cells of
      mesencephalonic origin, which give rise to GnRH-II (chicken-II GnRH) are
      evolutionarily conserved; might function as a neuromodulator involved in motor
      associated reproductive behaviors and acid-base balance. (3) Cells of
      diencephalonic origin, which give rise to GnRH-IV (seabream, medaka GnRH); they
      are localized in the anterior-basal OVLT-POA area and present only in advanced
      teleost fishes. GnRH-IV has been implicated in gonadal sex differentiation,
      gonadal maturation, LH/FSH secretion and territorial behavior. Advance teleost
      fishes for yet unknown functions might have acquired GnRH-IV. Although all GnRH
      subtypes participate in some aspect of reproduction; the precise function of each
      GnRH form still remains unclear.

PMID- 12508558
TI  - GnRH in the invertebrates: an overview.

PMID- 12508559
TI  - Structural and chemical guidance cues for the migration of GnRH neurons in the
      chick embryo.

PMID- 12508560
TI  - What defines the nervus terminalis? Neurochemical, developmental, and anatomical
      criteria.

PMID- 12508561
TI  - Angiogenesis in association with the migration of gonadotropic hormone-releasing
      hormone (GnRH) systems in embryonic mice, early human embryos and in a fetus with
      Kallmann's syndrome.

PMID- 12508562
TI  - Recent advances in the pathogenesis of Kallmann's syndrome.

PMID- 12508563
TI  - Differences in structure-function relations between nonmammalian and mammalian
      GnRH receptors: what we have learnt from the African catfish GnRH receptor.

PMID- 12508564
TI  - Regulation of GnRH and its receptor in a teleost, red seabream.

PMID- 12508565
TI  - Multiplicity of gonadotropin-releasing hormone signaling: a comparative
      perspective.
AB  - GnRH regulation of GtH synthesis and release involves PKC- and Ca(2+)-dependent
      pathways. There are differential signaling mechanisms in different cells, tissues
      and species. Signaling mechanisms involved in GnRH-mediated GtH release appear to
      be more conserved compared to that of GnRH-induced GtH gene expression. This may
      in part be due to different 5' regulatory regions on the GtH-subunit genes. Cell
      type specific expression of various signaling and/or exocytotic components may
      also be responsible for the observed differences in signaling between
      gonadotropes and somatotropes in the goldfish and tilapia pituitaries. However,
      this can not explain the observed differences in post receptor mechanisms for
      sGnRH and cGnRH-II in gonadotropes which is more likely to result from the
      existence of GnRH receptor subtypes. Support for this hypothesis is also provided
      by observations on mechanisms of autocrine/paracrine regulation of ovarian
      function by sGnRH and cGnRH-II in the goldfish ovary in which GnRH antagonists
      only block GnRH stimulation of oocyte meiosis and do not affect inhibitory
      effects of sGnRH. It should be easier to explain observed variations concerning
      GnRH-induced responses as more information becomes available on different types
      of GnRH receptors, and their distribution and function in mammals and non
      mammalian vertebrates.

PMID- 12508566
TI  - Gonadotropin-releasing hormone receptor: cloning, expression and transcriptional
      regulation.
AB  - In summary, isolation of GnRH receptor cDNA, its gene, and identification of
      regulatory elements in the flanking region of the gene have added to our
      knowledge regarding the tissue-specific expression of the GnRH receptor gene, and
      the mechanisms that mediate and influence its transcriptional regulation.
      However, the interactions of the different regulatory factors (nuclear factors)
      and the effects of these interactions on the regulation of the GnRH receptor gene
      remain unclear. Due to existence of multiple promoters and transcriptional start
      sites in human GnRH receptor gene and the lack of a human gonadotrope cell line,
      the precise promoter and transcriptional start sites in human pituitary, extra
      pituitary tissues and tumors have not yet been identified.

PMID- 12508567
TI  - Hypothalamic control of gonadotropin secretion.

PMID- 12508568
TI  - Gonadotropin-releasing hormone (GnRH) surge generator in female rats.

PMID- 12508569
TI  - Mechanisms of inhibition of LHRH release by alcohol and cannabinoids.

PMID- 12508570
TI  - Glutamatergic regulation of gonadotropin-releasing hormone neurons.

PMID- 12508571
TI  - Gonadotropin-releasing hormone (GnRH) neurons: gene expression and
      neuroanatomical studies.

PMID- 12508572
TI  - GnRH pre-mRNA splicing: role of exonic splicing enhancer.

PMID- 12508573
TI  - The GnRH neuron: molecular aspects of migration, gene expression and regulation.

PMID- 12508574
TI  - Physiology and release activity of GnRH neurons.

PMID- 12508575
TI  - A role for non-neuronal cells in synchronization of intracellular calcium
      oscillations in primate LHRH neurons.

PMID- 12508576
TI  - GnRH in the regulation of female rat sexual behavior.

PMID- 12508577
TI  - Nutrition, reproduction, and behavior.

PMID- 12508578
TI  - GnRH, brain mast cells and behavior.

PMID- 12508579
TI  - Vying for dominance: dynamic interactions control visual fixation and saccadic
      initiation in the superior colliculus.
AB  - By the time you have reached this point, your daily count of alternating saccades
      and fixations will have increased considerably. So too will have your
      understanding of the dynamic interactions model. In the superior colliculi,
      visual fixation and saccadic initiation may be viewed as independent motor plans
      that compete for dominance across the intermediate layers. Extrinsic input
      modifies a point location on the retinotopic motor map that is shaped into a
      motor plan through the intrinsic circuitry of the superior colliculi. Independent
      motor plans compete for selection in a push-pull fashion and when a saccadic plan
      ultimately reaches threshold, it produces a strong burst of action potentials
      that shuts down the remaining regions of the intermediate layers. Modifying the
      activity of the intermediate layers changes these dynamic interactions in
      predictable ways. Enhancing the activity of one region facilitates nearby
      locations and inhibits distant locations. Diminishing the activity of one region
      inhibits nearby locations and facilitates distant locations. Such effects have
      been demonstrated in the neurophysiological activity of single cells (Munoz and
      Istvan, 1998; Olivier et al., 1999) and in behavior (Hikosaka and Wurtz, 1985;
      Munoz and Wurtz, 1993b). In addition to explaining visual fixation and saccadic
      initiation during basic saccadic tasks, the dynamic interactions model can
      explain changes in the timing of saccadic initiation that are observed when this
      task is modified. Namely, the gap effect, or decreased saccadic reaction times as
      a consequence of a gap period, occurs because removing fixation decreases the
      activity of fixation regions and, correspondingly, increases the excitability of
      saccadic regions. Express saccades, are a special instance of such dynamic
      interactions, in which decreased fixation activity and heightened motor
      preparation signals cause the target-related activity to be translated into a
      saccadic signal immediately. Finally, the slowing of saccadic initiation for
      antisaccades, can be interpreted as the consequence of multiple competing signals
      across the intermediate layers. It should be emphasized that the dynamic
      interactions that we have described in this chapter are not limited to the
      superior colliculi. On the contrary, similar interactions take place at many
      levels of the neuraxis (Moschovakis et al., 1996; Leigh and Zee, 1999; Schall and
      Thompson, 1999; Hikosaka et al., 2000; Munoz et al., 2000; Glimcher, 2001;
      Scudder et al., 2002). At this juncture, however, the dynamic interactions
      involved in producing visual fixation and saccadic initiation are better
      understood in the superior colliculi because of its well-organized motor map and
      its well-characterized neuronal elements. Although we are a long way from
      understanding how the brain controls visual fixation and saccadic initiation, we
      have made substantial progress in understanding these behaviors in the superior
      colliculi.

PMID- 12508580
TI  - Neural control of saccades.
AB  - Quantitative models of the oculomotor plant and control of the saccadic eye
      movement system are presented in this chapter. Oculomotor plant models described
      here are linear, including a second-order model by Westheimer (1954), Bahill et
      al. (1980) and Enderle et al. (2000). The model of the saccade generator is
      initiated by the superior colliculus and terminated by the cerebellar fastigial
      nucleus that operates under a time optimal control strategy. A common mechanism
      for all types of saccades is described, including those with dynamic overshoot
      and glissadic behavior. Conflicting evidence exists regarding the operation of
      the excitatory burst neuron during saccades. The excitatory burst neuron operates
      within two states: complete inhibition, and without inhibition that is
      characterized by high firing at rates of up to 1000 Hz. While there is direct
      evidence of projections from the superior colliculus to the paramedian pontine
      reticular formation, there is conflictory evidence regarding the connections from
      the superior colliculus to the excitatory burst neuron, with the most recent
      experimental results supporting no direct connections. A model of the excitatory
      burst neuron is described using a Hodgkin-Huxley model of the neuron that fires
      at 1000 Hz automatically and without stimulation when released from inhibition.
      SIMULINK simulations using this neuron model have all of the characteristics of
      the excitatory burst neuron firing rate during a saccade. This model eliminates
      the need to introduce BIAS inputs that causes bursting in some models of the
      saccade generator. Such a model is also appropriate for modeling the Omnipause
      neurons.

PMID- 12508581
TI  - The latency of saccades toward auditory targets in humans.
AB  - Auditory targets can be used to evoke saccadic eye movements since they provide a
      position reference signal in space. Comparison of the characteristics of saccades
      evoked by both visual and auditory stimuli can give further information on the
      oculomotor control system. In particular, the latency of auditory saccades evoked
      in different experimental situations, such as the step, gap and overlap
      protocols, and with different starting positions of the eyes in the orbit can
      provide useful insight into the central processing underlying saccade generation.
      The aim of this chapter is to provide a review of auditory saccade
      characteristics and to present latency data obtained in human subjects in
      different experimental conditions.

PMID- 12508582
TI  - Contribution of the primate prefrontal cortex to the gap effect.
AB  - The introduction of a brief temporal gap between the disappearance of the initial
      fixation point and the presentation of a peripheral target leads to a general
      reduction in saccadic reaction times (SRTs), known as the gap effect. Moreover,
      extremely short latency express saccades frequently occur in this paradigm.
      Disorders of the prefrontal cortex (PFC) are often associated with increased
      numbers of express saccades and an inability to suppress reflexive saccades. To
      investigate the role of the PFC in the gap effect and in express saccade
      generation, we trained two rhesus monkeys on a gap saccade task in which the
      initial fixation point (FP) disappeared 200 ms or 600 ms before a peripheral
      stimulus appeared either 8 degrees to its left or right side. We recorded from
      the lateral PFC (areas 8 Ar and 46) in both monkeys the activity of 214 neurons,
      84 (39%) of which exhibited task-related activity. These neurons could be further
      categorized into separate groups based on their discharge behaviour: fixation
      neurons with a decrease in activity during the gap (27%), FP offset neurons
      (12%), preparatory neurons with an increase in activity during the gap (30%),
      visual neurons (6%), post-saccadic neurons (8%), and reward-related neurons
      (12%). There were no obvious differences in the topography of these groups.
      Significant differences between express and regular saccade trials were found for
      fixation-related neurons. These neurons had a lower activity during the gap prior
      to the generation of contralateral express saccades. We hypothesize that a
      reduction in the activity of fixation-related neurons in the PFC may contribute
      to the elevated rate of express saccades in prefrontal disorders.

PMID- 12508583
TI  - Influence of stimulus characteristics on the latency of saccadic inhibition.
AB  - Participants read or performed visual search while the normal task display was
      replaced for 33 ms by a transient image at random intervals. This produced a
      sharp reduction in saccadic frequency (saccadic inhibition) beginning as early as
      70 ms following the display change. It was found that the latency of inhibition
      onset was determined by the difference between the normal and transient images,
      with changes in high spatial frequency content of the display resulting in longer
      latencies than changes in low spatial frequencies. Luminance changes evoked the
      fastest inhibition onset regardless of the spatial frequency content of the
      display change.

PMID- 12508584
TI  - Commentary: saccadic eye movements: overview of neural circuitry.
AB  - Recent neuroanatomical, neurophysiological, clinical, and brain imaging studies
      have generated a wealth of data describing the neural control of saccadic eye
      movements and visual fixation. These studies have identified many of the cortical
      and subcortical structures involved in controlling the behavior. Critical nodes
      in the network include regions of the parietal and frontal cortices, basal
      ganglia, thalamus, superior colliculus, cerebellum, and brainstem reticular
      formation. Specific functions are likely not localized to only one brain area,
      but rather, they may be distributed across multiple areas. This commentary is
      used to review briefly the neural circuitry controlling saccadic eye movements
      and visual fixation.

PMID- 12508585
TI  - Converging evidence for the detection of change without awareness.
AB  - In this chapter, we explore the possibility that changes can be registered by the
      visual system and can influence behavior even in the absence of conscious
      awareness. We begin by describing the basic phenomenon of change blindness,
      introduce a framework for discussing some of the key issues relating to change
      detection as a whole, and then examine the main lines of evidence that point to
      the existence of implicit change detection.

PMID- 12508586
TI  - Blinks, blanks and saccades: how blind we really are for relevant visual events.
AB  - We report on a study in which subjects viewed color video stills of natural
      traffic situations while eye movements were recorded. A display change could
      occur randomly during three different occlusion modes--blinks, blanks and
      saccades--or during a fixation. These changes could be either relevant or
      irrelevant with respect to the traffic safety situation. Furthermore we
      contrasted insertions and deletions. All occlusion modes appeared equivalent
      concerning detection rate and detection time, and only differed from the fixation
      condition. The results also show that the detection of relevant changes was more
      likely and faster than that of irrelevant ones. However, even relevant
      insertions, which were almost always detected, were around 180 ms longer to
      report when they occurred during an occlusion. Furthermore, the detection of
      relevant changes was fairly stable across a wide range of the visual field,
      whereas irrelevant changes were less well detected, the further away from the
      fovea they occurred. We close with an outlook on a follow-up study where only
      relevant insertions and the blank occlusion were used in a driving simulator
      environment. Surprisingly, we found an advantage in change detection rate and
      time with blanks compared to the control condition. Change detection was also
      good during blinks, but not in saccades.

PMID- 12508587
TI  - Multiple-object permanence tracking: limitation in maintenance and transformation
      of perceptual objects.
AB  - Research on change blindness and transsaccadic memory revealed that a limited
      amount of information is retained across visual disruptions in visual working
      memory. It has been proposed that visual working memory can hold four to five
      coherent object representations. To investigate their maintenance and
      transformation in dynamic situations, I devised an experimental paradigm called
      multiple-object permanence tracking (MOPT) that measures memory for multiple
      feature-location bindings in dynamic situations. Observers were asked to detect
      any color switch in the middle of a regular rotation of a pattern with multiple
      colored disks behind an occluder. The color-switch detection performance
      dramatically declined as the pattern rotation velocity increased, and this effect
      of object motion was independent of the number of targets. The MOPT task with
      various shapes and colors showed that color-shape conjunctions are not available
      in the MOPT task. These results suggest that even completely predictable motion
      severely reduces our capacity of object representations, from four to only one or
      two.

PMID- 12508588
TI  - What information survives saccades in the real world?
AB  - Recent change detection research demonstrates impressively that we do not retain
      and fuse the pictorial content of successive fixations. This raises two distinct
      issues: (1) when and how is point-by-point information lost or replaced? and (2)
      might more abstract information be extracted and retained from fixations? In this
      chapter I explore both of these issues. I consider the evidence for a very short
      term richly detailed visual representation of the current target of fixation that
      survives the saccade but is overwritten by the content of each new fixation
      shortly after it begins. The possibility of abstract representations of the
      visual surroundings is then discussed. Under conditions of competitive, parallel
      processing, as are present in real life situations, multiple types of information
      are extracted and retained from complex natural scenes. Time courses for
      extraction vary between different types of information. The inclusion of eye
      movement data reveals a crucial role for fixations in information extraction. The
      data suggest that information assimilation into the representations tested here
      is dominated by the fovea and is integrated and accumulated from multiple
      foveations. From these studies we are able to construct a rudimentary framework,
      in which representational faithfulness and richness depend upon fixation history
      of that part of the visual scene, thus producing an efficient and potentially
      task-specific representation.

PMID- 12508589
TI  - Transsaccadic memory of position and form.
AB  - Why and how people perceive the visual world as continuous and stable, despite
      the gross changes of its retinal projection that occur with each saccade, is one
      of the classic problems in perception. In the present paper, we argue that an
      important factor of visual stability and transsaccadic perception is formed by
      the reafferent visual information, i.e., the visual display that is present when
      the eyes land. After a review of some of the relevant theoretical, behavioural
      and physiological research on space constancy, saccadic suppression and
      transsaccadic memory, three experiments are presented. In a first experiment, we
      study the effect of an extended horizontal bar covering the target area for a
      short period after the saccade on saccadic suppression of image displacement. The
      results show that the bar acts just like a temporary blanking of the saccade
      target, leading to a strong reduction of saccadic suppression. In the second
      experiment, we show that any object that is present immediately after the saccade
      can establish a spatial reference, even if it is dissimilar to the saccade
      target. In a third experiment we study, with a similar approach, the effect of
      blanking and postsaccadic information on transsaccadic integration of form
      information. The data demonstrate that a localized postsaccadic object tends to
      replace the content of transsaccadic memory.

PMID- 12508590
TI  - Transsaccadic memory for visual object detail.
AB  - When we move our eyes around in real-world scenes, we typically have several
      peripheral previews of an object before we direct our eyes straight at the
      object. Numerous studies on transsaccadic memory have investigated whether there
      is any evidence for the integration of peripheral object information acquired
      presaccadically with foveal object information acquired postsaccadically. We
      review this evidence to illustrate the currently dominant view that transsaccadic
      object memory is sparse and contains little visual object detail. However, based
      on some recent studies of the role of postsaccadic stimulus blanking in
      transsaccadic change detection, we hypothesize that transsaccadic object memory
      involves the automatic emergence of a visual analog: a high-capacity, non
      selective, internal representation of visual object detail. This hypothesis is
      tested by examining cued detection of intrasaccadic changes in the in-depth
      orientation of objects in scenes. The data provide preliminary support for the
      presence of the visual analog, but also show that its functionality is strictly
      limited by attentional and temporal constraints on the process of reading out
      information from the visual analog.

PMID- 12508591
TI  - Commentary: changes.
AB  - It is argued that change perception can provide a powerful way to explore various
      aspects of vision, such as visual attention and the accumulation of information
      across saccades. Several studies of change perception are discussed, and their
      results consolidated with existing knowledge to cast new light on our
      understanding of the visual system.

PMID- 12508592
TI  - Non-target influences on the initiation of smooth pursuit.
AB  - Smooth pursuit is usually regarded as a relatively stereotyped oculomotor
      response in which the early part of the response reflects primarily the
      properties of the visual stimulus and cortical motion processing. We have
      investigated pursuit initiation in human subjects using the gap paradigm to alter
      fixation conditions, and single stationary distractors to alter visual context.
      The results suggest that a number of processes, distinct from motion processing,
      are involved in pursuit initiation. The processes which are modified by gaps and
      distractors are closely related and interact with each other. They may be shared
      with the saccade system.

PMID- 12508593
TI  - Integration of motion cues for the initiation of smooth pursuit eye movements.
AB  - To clearly see a moving object, an observer must rotate his or her eyes with a
      velocity that matches that of the object. Such rotations are called smooth
      pursuit eye movements, and they depend critically on the ability of the primate
      brain to integrate information about object velocity from various local motion
      signals. When the local motion signals are in conflict, it is possible to use
      smooth pursuit eye movements as a continuous read-out of the motion integration
      process. This review discusses the results of recent behavioral experiments that
      have taken this approach, along with relevant neurophysiological and
      computational studies.

PMID- 12508594
TI  - The role of expectancy and volition in smooth pursuit eye movements.
AB  - The most important factor allowing the generation of pursuit eye movements prior
      to target onset is confidence in the likelihood of imminent target appearance. We
      show how these anticipatory pursuit responses are essentially ballistic motor
      primitives and how the signal that drives them in normally defined by stored
      information concerning target speed, duration and direction. But we also show how
      static cues may be used to grade the level of these motor primitives 'on-line'.
      We further demonstrate that, when concatenated, these graded motor primitives can
      be rapidly combined to form predictive smooth movement trajectories in response
      to complex multi-ramp sequences.

PMID- 12508595
TI  - Visual and cognitive control of attention in smooth pursuit.
AB  - In this chapter, we describe the role of attention in the control of smooth
      pursuit eye movements. As a voluntary and continuous eye movement, smooth pursuit
      is driven by both visual and cognitive signals. Here we show that whereas the
      entire process of smooth pursuit requires visual attention, the post-onset phase
      of the initiation and the maintenance smooth pursuit are under an additional
      sustained non-visual cognitive attention control. The temporal dynamics of these
      complementary controls of visual and non-visual cognitive attention support the
      continuous generation of smooth pursuit so that eye tracking of a moving target
      can be prompt and accurate.

PMID- 12508596
TI  - The allocation of attention during smooth pursuit eye movements.
AB  - The spatial-temporal allocation of attention during smooth pursuit eye movements
      is poorly understood. In this chapter we review evidence showing that attention
      contributes to both saccades and smooth pursuit. We then discuss results from our
      own recent studies using a dual-task paradigm in which subjects pursued a moving
      stimulus and pressed a button when targets appeared in the periphery. The results
      from these studies are consistent with the hypothesis that the allocation of
      attention is biased to a location just in front of the pursuit stimulus and that
      this bias can be altered by pursuit velocity.

PMID- 12508597
TI  - Commentary: smooth pursuit eye movements: from low-level to high-level vision.
AB  - If an object of great interest moves in our environment, we are able to elicit
      smooth pursuit eye movements that keep the image of the moving object stationary
      on our fovea. The processing of visual motion underlying the execution of smooth
      pursuit eye movements is very similar to the processing underlying the perception
      of visual motion. During initiation of smooth pursuit, an averaging across all
      available motion information occurs. Cognitive factors including attention,
      prediction and learning are able to influence the execution of smooth pursuit.
      The pursuit target trajectory in space is represented in the discharge rates of
      neurons in the posterior parietal cortex of rhesus monkeys.

PMID- 12508598
TI  - Cortical frames of reference for eye-hand coordination.
AB  - To reach for an object the brain must transform visual input from the eye into
      motor output of the arm. Recent neurophysiological experiments have shown that
      this transformation maps onto a network of brain areas including the posterior
      parietal (PPC) and premotor (PMC) cortices. In this chapter, we review evidence
      from our own experiments which demonstrate that this network can only partially
      complete the transformation when the eye and limb movement amplitudes are
      dissociated. We also discuss the effects of disrupting either the PPC or PMC
      using transcranial magnetic stimulation (TMS) on the ability to carry out the
      transformation successfully.

PMID- 12508599
TI  - Neuropsychological perspectives on eye-hand coordination in visually-guided
      reaching.
AB  - Substantial progress has been made in understanding the neural control of
      movement in the past 30 years. Lower cost technology for tracking movements of
      the eyes and the hands has increased our understanding of these two systems and
      their interactions in both neurologically intact individuals and non-human
      primates. Nevertheless the neuropsychology of eye-hand coordination during
      visually-guided tasks such as reaching and grasping remains relatively
      understudied. This chapter reviews some of the relevant neurophysiology and
      neuropsychology of eye-hand coordination during visually-guided reaching. Current
      models emphasising coordinate transformations are discussed in light of new
      patient data showing a particular type of failure of eye-hand coordination during
      reaching.

PMID- 12508600
TI  - Visuomotor transformations for eye-hand coordination.
AB  - In recent years the scientific community has come to appreciate that the early
      cortical representations for visually guided arm movements are probably coded in
      a visual frame, i.e. relative to retinal landmarks. While this scheme accounts
      for many behavioral and neurophysiological observations, it also poses certain
      problems for manual control. For example, how are these oculocentric
      representations updated across eye movements, and how are they then transformed
      into useful commands for accurate movements of the arm relative to the body?
      Also, since we have two eyes, which is used as the reference point in eye-hand
      alignment tasks like pointing? We show that patterns of errors in human pointing
      suggest that early oculocentric representations for arm movement are remapped
      relative to the gaze direction during each saccade. To then transform these
      oculocentric representations into useful commands for accurate movements of the
      arm relative to the body, the brain correctly incorporates the three-dimensional,
      rotary geometry of the eyes when interpreting retinal images. We also explore the
      possibility that the eye-hand coordination system uses a strategy like ocular
      dominance, but switches alignment between the left and right eye in order to
      maximize eye-hand coordination in the best field of view. Finally, we describe
      the influence of eye position on eye-hand alignment, and then consider how head
      orientation influences the linkage between oculocentric visual frames and
      bodycentric motor frames. These findings are framed in terms of our 'conversion
      on-demand' model, which suggests a virtual representation of egocentric space,
      i.e. one in which only those representations selected for action are put through
      the complex visuomotor transformations required for interaction with actual
      objects in personal space.

PMID- 12508601
TI  - Implications of distracter effects for the organization of eye movements, hand
      movements, and perception.
AB  - The end positions of eye and hand movements were both drawn towards a distracter
      that was presented nearby the target. They thus showed a so-called global effect.
      In contrast, perception was not influenced by the presence of a distracter. These
      results are discussed with regard to the question whether eye, hand, and
      perception are based on shared or separate target representations and readout
      triggers. We conclude that separate representations and readout triggers for eye
      and hand are the most likely case.

PMID- 12508602
TI  - Visual short-term memory and motor planning.
AB  - Despite extensive experimental work showing that memory for visual information in
      prior fixations is limited, the nature and content of the information maintained
      across fixations, when vision functions in its natural context, is not well
      determined. To gain insight into what memory representations might be needed to
      support vision in the natural world, we examined eye and hand movements while
      subjects made a sandwich and while they copied a toy model in a virtual
      environment. Patterns of eye-hand coordination and fixation sequences suggest the
      need for planning and coordinating movements over a period of a few seconds.
      Since the movement plan is initiated when the eye is in a different position from
      that when the movement itself is made, the planning must be in a coordinate frame
      that is independent of eye position. Movement planning thus requires a
      representation of the spatial structure in a scene that is built up over
      different fixations.

PMID- 12508603
TI  - Commentary: coordination of eye and hand in time and space.
AB  - Every day of our lives starts with a succession of actions that require eye-hand
      coordination. From the time we try to turn off the alarm clock and get dressed,
      to putting toothpaste on the brush and preparing coffee: all these goal-directed
      hand movements need to be coordinated with the information from the eye. When
      performing such simultaneous goal-directed eye and hand movements, both the time
      and location at which eye and hand land on the object need to be harmonized. For
      better localizing the alarm clock, we need to see it before we hit it. In order
      to use this visual information for an accurate hand movement, we need the eye to
      land on the same position, i.e. eye and hand both need to be on the alarm clock
      instead of the water glass. These two aspects, temporal and spatial coordination,
      have encouraged a great deal of research. On the following pages, we will
      summarize a number of findings on how this coordination could be achieved.

PMID- 12508604
TI  - Visual search in long-term cannabis users with early age of onset.
AB  - The present research tested the hypothesis that there is a specific deficit in
      visual scanning in chronic users of cannabis with early onset of their drug
      consumption (age 14 to 16). 17 users and 20 control participants were asked to
      search for targets on a 5 x 5 stimulus array while their eye movements were
      monitored. Cannabis users showed less effective search behavior, including longer
      response times and more fixations at about the same error level. Search patterns
      were more conservative and included more frequent reinspections of previously
      fixated areas. In sum, the results point to two loci of adverse effects: an
      impairment in visual short-term memory, and less effective visual processing at a
      more strategic, top down controlled level.

PMID- 12508605
TI  - Visual search in patients with left visual hemineglect.
AB  - In patients with hemi-spatial neglect eye movement patterns during visual search
      reflect not only inattention for the contralesional hemi-field, but interacting
      deficits of multiple visuo-spatial and cognitive functions, even in the
      ipsilesional hemi-field. Evidence for these deficits is presented from the
      literature and from saccadic scan-path analysis during feature and conjunction
      search in 10 healthy subjects and in 10 patients with manifest or recovered left
      visual neglect due to right-hemispheric stroke. Deficits include (1) a rightward
      shift of spatial representation, (2) deficient spatial working memory and failure
      of systematic search strategies, leading to multiple re-fixations, more after
      frontal lesions, and (3) a reduced spotlight of attention and a deficient pop-out
      effect of color, more after temporo-parietal lesions.

PMID- 12508606
TI  - Saccadic adaptation in neurological disorders.
AB  - The role of saccadic adaptive processes in recovery from the effects of various
      neurological disorders, such as myasthenia gravis, extraocular muscle palsies,
      and age-related macular degeneration, is reviewed. Studies of clinical
      populations (e.g. cerebellar disease, mild closed head injury, and opsoclonus) in
      which intrasaccadic displacement of visual targets has been used to stimulate
      adaptation are also reviewed. Our own data from such a study of 12 subjects with
      Parkinson's disease are presented, showing that visually guided adaptation is
      preserved in PD while memory-guided adaptation is impaired. This supports a model
      in which different brain regions subserve adaptation in different tasks.

PMID- 12508607
TI  - Saccade sequences as markers for cerebral dysfunction following mild closed head
      injury.
AB  - Diffuse axonal injury caused by mild closed head injury (CHI) is likely to affect
      the neural networks concerned with the planning and execution of sequences of
      memory-guided saccades. Thirty subjects with mild CHI and thirty controls were
      tested on 2- and 3-step sequences of memory-guided saccades. CHI subjects showed
      more directional errors, larger position errors, and hypermetria of primary
      saccades and final eye position. No deficits were seen in temporal accuracy
      (timing and rhythm). These results suggest that computerized tests of saccade
      sequences can provide sensitive markers of cerebral dysfunction after mild CHI.

PMID- 12508608
TI  - Cognition and the inhibitory control of saccades in schizophrenia and Parkinson's
      disease.
AB  - Historically, various lines of evidence have converged on the view that the brain
      expends much of its neural resources on inhibiting its own activity in a critical
      step towards the cognitive control of behaviour. The loss of inhibitory control
      is widely reported in neurological and psychiatric disorders; however, the
      consequences of reduced inhibition in terms of wider cognitive effects on
      cognitive control operations such as planning, abstract thought, working memory
      and the ability to appreciate the perspective of others ('theory of mind') has
      been widely overlooked. The antisaccade paradigm examines the conflict between a
      prepotent stimulus that produces a powerful urge to fixate the target, and the
      overriding goal to 'look' in the opposite direction. In this chapter we
      illustrate how this paradigm is increasingly used to explore the relationship of
      inhibitory control and cognition in Parkinson's disease, schizophrenia and
      healthy participants. Evidence is presented that is consistent with the theory of
      cognitive inhibition as a distinct process that can be dissociated from working
      memory. We conclude that the inhibitory control of saccadic eye movement should
      be studied in the wider context of cognitive operations.

PMID- 12508609
TI  - Control of volitional and reflexive saccades in Tourette's syndrome.
AB  - We hypothesized that Tourette's syndrome (TS) patients would display abnormal
      control of saccades because of overlap between brain areas suspected in TS
      pathophysiology and those involved saccade control. Subjects were required to
      look toward (pro-saccade) or away from (anti-saccade) a visual target. Saccadic
      reaction times were elevated among TS subjects in all tasks. The occurrence of
      reflexive pro-saccades in the immediate anti-saccade task was normal, suggesting
      that the ability to inhibit reflexive saccades was not impaired in TS. However,
      timing errors (eye movements made prior to GO signal in delayed saccade tasks)
      were increased in TS indicating that ability to inhibit or delay planned motor
      programs is significantly impaired in TS.

PMID- 12508610
TI  - Oculomotor control in a group of very low birth weight (VLBW) children.
AB  - VLBW infants are at risk of lesions including intraventricular haemorrhage and
      periventricular leucomalacia. Those with normal IQ still present with reading
      difficulties. Oculomotor performance was assessed on 14 VLBWs (IQ > 85) and 15
      full-term age-matched controls. Anti-saccade errors were significantly higher for
      the VLBWs (78%) compared to full terms (62%) (P = 0.02). Smooth pursuit latency
      was longer for the VLBWs compared to the full terms. Greater anti-saccade errors
      may be indicative of a lesion affecting the frontal cortex or developmental
      delay. Oculomotor deficits in VLBW children may be associated with the higher
      incidence of reading difficulties that have been reported.

PMID- 12508611
TI  - A new framework for investigating both normal and abnormal eye movements.
AB  - Any comprehensive framework for understanding eye movements has to include both
      normal and abnormal eye movement behaviour. One approach which is applicable to
      the entire range of oculomotor behaviour is provided by the techniques of
      nonlinear dynamics. The stability of models of the oculomotor system can be
      analysed in terms of the characteristics of their fixed points and periodic
      orbits, and the method of delays can be used to recover such parameters from
      measurements of eye position. Within this framework, quantitative comparisons can
      be made between the predictions of different models, and both normal and clinical
      eye movement recordings.

PMID- 12508612
TI  - Commentary: eye movement research with clinical populations.
AB  - The preceding set of chapters span the disciplines of neurology and psychiatry,
      and provide a diverse introduction to clinical eye movement research. They
      illustrate how oculomotor paradigms can be used to learn about acute and chronic
      perturbations in brain function, disturbances in brain development, disturbances
      in sensorimotor as well as cognitive systems, and the effects of therapeutic and
      illicit drugs on brain function. This commentary discusses these contributions,
      provides an overview of broad methodological issues involved in applying eye
      movement studies to psychiatric populations using the antisaccade task as an
      exemplar, and considers the potential of collaborations between eye movement and
      brain imaging researchers to advance understanding of clinical eye movement
      abnormalities and of what they reveal about the organization of the oculomotor
      system.

PMID- 12508613
TI  - Biotechnology.

PMID- 12508614
TI  - Functional restoration by excision arthroplasty in temporomandibular joint
      ankylosis--a report of 35 cases.
AB  - OBJECTIVE: To evaluate the long term functional results of excision arthroplasty
      in treatment of temporomandibular joint (TMJ) ankylosis. MATERIAL AND METHODS:
      This retrospective study includes 35 patients of TMJ ankylosis who were treated
      by excision arthroplasty and followed for a maximum period of eight years after
      surgery. Past trauma was documented as a major etiological factor in 63% cases.
      Fibrous ankylosis & unilateral involvement was found to be more common.
      Peroperatively a gap of 1 1/2 to 2 cm was created. The results were assessed
      according to a criteria based on inter-incial month opening, deviation of jaw and
      complications. They were satisfactory in 29 cases and there were 3 recurrences.
      CONCLUSION: Childhood trauma is a major cause of TMJ ankylosis in India. Long
      term results of excision arthroplasty are satisfactory & comparable to other
      surgical modalities that are in vogue, provided the patients are operated when
      young, the ankylosis is in early stage, gap created is adequate and post
      operative exercise regimen is followed diligently.

PMID- 12508615
TI  - Plasmapheresis: an effective therapy for refractory hyperthyroidism in the
      elderly.
AB  - Hyperthyroidism in the elderly often presents diagnostic challenges. Elderly
      patients rarely present with classical signs and symptoms of hyperthyroidism.
      More commonly, their presentation is ayical which leads to a delay in making a
      diagnosis. Such delays can sometimes decrease the functional capacity of the
      affected patient and reduce their chance for recovery. Herein we report a 66-year
      old woman whose diagnosis of hyperthyroidism was delayed. Standard therapies were
      ineffective. Plasmapheresis was performed to control the manifestations of the
      hyperthyroid state, resulting in improvement in the patient's condition.

PMID- 12508616
TI  - Infantile tremor syndrome and zinc deficiency.
AB  - Infantile tremor syndrome is characterized by coarse tremors, mental and physical
      retardation, light colored brown hair, skin pigmentation and anemia. Amongst the
      theories proposed for the etilogy of the disorder, the nutritional theory is most
      accepted. In this case report, we have presented a fourteen-month-old male child
      with ITS and documented zinc deficiency. Though most of the previous workers have
      proposed vitamin-B12 deficiency as the etimology for ITS, our report suggests
      that zinc deficiency could also have a causative role.

PMID- 12508617
TI  - Treatment of tuberculosis: is our knowledge adequate?
AB  - Tuberculosis remains a global problem even after the excellent drugs available to
      cure it. Inappropriate and inadequate treatment leads to acquired drug
      resistance, which may result in treatment failure and spread of resistant
      organisms to other persons. Our study was aimed at finding out the current status
      of knowledge, attitude and practice of resident doctors and consultants medical
      institutes in two different parts of India. All the residents and consultants
      were given a questioner containing twenty questions based on WHO guidelines for
      treatment of tuberculosis and the positive responses were calculated. The results
      were tabulated in the form of percentage of correct responses to individual
      queries. 80 doctors responded by filling up the questioner. None of the
      respondents could correctly answer all 20 questions. Only four could answer more
      than 75% questions correctly and only 17 could answer at least 50% of the
      questions correctly. 17.5% respondents could not even answer 25% questions
      correctly. The details of answer to individual queries presents a dismal picture.
      This study looked at their present knowledge attitude and treatment practice of a
      very common but serious disease like tuberculosis and the inadequacy of our
      knowledge in this regards should make us think about reshaping our policies for
      managing tuberculosis.

PMID- 12508618
TI  - Sclerosing mediastinitis: a case report.
AB  - A rare case of sclerosing mediastinitis in a 38 year old male is described. This
      interesting case illustrates how a seemingly benign fibrosing condition may lead
      to disastrous and fatal complications.

PMID- 12508619
TI  - Gene patents--update.

PMID- 12508620
TI  - Rare cause for short stature--Kallmann's syndrome--a case report.
AB  - Kallmann's syndrome is a neuroendocrine disorder, characterized by
      hypogonadotropic hypogonadism with hyposmia. We report a 27 year old male who
      presented with short stature and pain in the lumbar region. On detailed
      evaluation he had growth retardation, features of hypothalamic hypogonadism as
      evidenced by endocrimological tests and anosmia since birth. He had co-existent
      caries spine T10,T11 causing pain in the lumbar region-MRI brain showed normal
      olfactory pathway while the response to nasal stimulants was markedly attenuated.
      We present this case for its very care occurrence in the eastern part of the
      world and the typical feature being normal MRI brain with functional defect of
      the olfactory pathway.

PMID- 12508621
TI  - Translocation Down syndrome.
AB  - Cytogenetic investigations carried on 1021 cases of Down syndrome revealed
      translocation in 46 cases. The most frequent was of t(14;21) and t(21;21) types.
      Most of the translocation DS cases (n = 31) were born to younger mother's (< 25
      years), when compared to pure trisomy 21 DS cases. Parental karyotypes, family
      history and parental ages has helped us greatly in offering genetic counseling,
      prenatal diagnosis and estimating the risk for the next conception.

PMID- 12508622
TI  - "Euvolemic hyponatremia"--3 case reports and approach to management.

PMID- 12508623
TI  - Environmental risk factors: a study in Kutch region.
AB  - The environment risk factors particularly drinking water status and vector
      breeding status. In the earthquake--affected villages in Kutch region are
      presented.

PMID- 12508624
TI  - Evaluation of minimum inhibitory concentration of quinolones and third generation
      cephalosporins to Salmonella typhi isolates.
AB  - A total of 323 Salmonella typhi isolates (261 isolates obtained during 1995-99
      from Ludhiana and 62 randomly selected isolates obtained between 1980-99 from
      Chandigarh) were analyzed for drug resistant pattern. S. typhi isolates prior to
      1986 were sensitive to all the antimicrobials tested by disc diffusion method.
      Most common multidrug resistance pattern noticed was ACCo T i.e. resistance to
      ampicillin, Chloramphenicol, cotrimoxazole and tetracycline. This study has
      revealed that withdrawal of chloramphenicol due to high level of resistance
      during 1990-94, has led to re-emergence of 43-93 percent chloramphenicol
      sensitive mutants during 1995-99. Two S. typhi isolates in 1995 and one in 1999
      from Ludhiana depicted resistance to ciprofloxacin. Susceptibility of S. typhi
      isolates to third generation cephalosporins ranged between 87 to 100 per cent.
      There was a gradual increase with time period in mean minimum inhibitory
      concentration (MIC) of ciprofloxacin as it increased from 0.066 ug/ml for 1980-83
      S. typhi isolates to 0.13 ug/ml for the 1996-99 isolates. Similarly, cefotaxime
      mean MIC for 1980-83 isolate was 0.172 ug/ml which further increased up to 0.32
      ug/ml for S. typhi isolates encountered between 1996-99. In contrast, mean MIC
      value of 0.62 ug/ml of Ceftriaxone remained unchanged irrespective of the year of
      isolation of S. typhi isolates.

PMID- 12508625
TI  - Differential effects of benzodiazepines on immune responses in non-stressed and
      stressed animals.
AB  - Benzodiazepines (BZDs) used extensively as antianxiety agents are known for their
      low toxicity. However, a long lasting depression of mitogen stimulated secretion
      of macrophage-derived cytokines has been shown in offsprings of rats that were
      exposed to diazepam during pregnancy. The Present study investigates the effects
      of long term administration of diazepam and alprazolam on humoral and cell
      mediated immune responses in adult male Wistar rats and Swiss albino mice.
      Administration of diazepam (5 mg/kg/day x 7-14 d) and alprazolam (1 mg/kg/day x 7
      14 d) produced a significant reduction of anti-SRBC antibody titre, a measure of
      humoral immune response, and foot pad thickness and % leucocyte migration
      inhibition (% LMI), measures of cell-mediated immune responses. Administration of
      diazepam (5 mg/kg, i.p.) or alprazolam (1 mg/kg, i.p.) before subjecting the
      animals to restraint stress (RS) reversed the immunosuppressive effects of RS.
      Both per se immunosuppressive effects and attenuation of RS-induced
      immunosuppression of BZDs was antagonized by flumazenil (10 mg/kg, i.p.), a
      central BZD receptor antagonist. Thus, BZDs appear to modulate the immune system
      in non-stressed and stressed adult animals in a differential manner and these
      effects are mediated via central benzodiazepine receptors.

PMID- 12508626
TI  - DOTS strategy for control of tuberculosis epidemic.
AB  - The article reviews the elements of the DOTS strategy to control the tuberculosis
      epidemic WHO declared TB" a global emergency" in 1993, the impact of which is
      worsened by the emergence of multi drug-resistant TB (MDR-TB) and the spread of
      HIV/AIDS. DOTS (directly-observed treatment, short-course) is an intermittent,
      supervised system of drug-intake by patient, which eliminates drug-default. It
      has been described by WHO as "the most important public health breakthrough of
      the decade in terms of lives saved" The 5 major components of DOTS are i)
      Political will, ii) High-quality microscopy, iii) Uninterrupted supply of short
      course chemotherapy drugs, iv) Directly--observed chemotherapy regimen use, v)
      Systemic monitoring using the TB cure rate. Standardized, intermittent DOTS
      regimens are classified using three categories of disease. The main advantages of
      DOTS are (i) Cure rates of upto 95%, (ii) Prevention of MDR--TB emergence, (III)
      Improvement of longevity of AIDS patients by TB control, (iv) It is "one of the
      most cost-effective of all health interventions", according to World Bank.

PMID- 12508627
TI  - DOTS versus self administered therapy (SAT) for patients of pulmonary
      tuberculosis: a randomised trial at a tertiary care hospital.
AB  - Tuberculosis is a major public health problem in a developing country like India,
      it is made worse by poor adherence to and frequent interruption of treatment.
      Treatment of tuberculosis requires strict discipline in order to eradicate
      mycobacteria and to cure the disease. In the present study we have conducted a
      randomized control trial, to compare the effectiveness of Directly Observed
      Therapy Short Course (DOTS) versus Self Administered Therapy (SAT) in a tertiary
      care hospital.

PMID- 12508628
TI  - Proteomics.

PMID- 12508629
TI  - Mental and neurological disorders. World Health Organization fact sheet no. 265
      December 2001.

PMID- 12508630
TI  - Euvolemic hyponatremia--3 case reports and approach to management.

PMID- 12508631
TI  - Topical phenytoin in diabetic ulcers: a double blind controlled trial.
AB  - Data of 57 patients who completed the trial and 13 who did not, were analysed.
      With phenytoin, there was a marginal: increase in the reduction of mean ulcer
      area and acceleration of effect 3rd on 4th week. With control: the number
      completing the trial was larger: response to treatment was better in grade II
      ulcers, Table IV. This study has the hall marks of a real clinical trial, has
      raised the possibility of wound healing properties of phenytoin and confirms the
      results of others.

PMID- 12508632
TI  - Care of burns: a knowledge, attitude and practice study among match industry
      workers.

PMID- 12508633
TI  - Effect of Saral meditation on intelligence, performance and cardiopulmonary
      functions.
AB  - Meditation is a mental exercise to improve mental faculty. Present attempt was to
      evaluate effect of Saral Meditation on development of intelligence, academic
      performance & cardiopulmonary functions. Results show significant improvement in
      development of intelligence and academic performance. There was apparent
      improvement in confidence and they were free from anxiety. There were also
      considerable changes in psychomotor ability and cardiopulmonary functions
      however, result was not significant.

PMID- 12508634
TI  - Life style and morbidity profile of geriatric population in an urbans community
      of Delhi.
AB  - A cross-sectional study was carried to find out the lifestyle pattern and
      morbidity profile of geriatrics residing in urban community of Vikram Nagar,
      Delhi. Women constituted 56.25% and men 43.75% of a total of 128 study subjects.
      Hindus were 89.06% and Sikhs 10.93%. Age group of 60-75 years accounted for most
      of the study population. 85% of the subjects complained of one or more health
      problems. 90.62% of them suffered from dental problems. A significantly higher
      proportion of women suffered from problems of locomotion/joints and anemia as
      compared to men whereas genitourinary problems were higher in men as compared to
      women. 42.55 of the women and 30.76% of the men were obese. Current smokers
      constituted 15.62% of the women and 30.76% of the men were obese. Current smokers
      constituted 15.62% of the population whereas 30.35% of the men were current
      consumers of alcohol. 12.5% used tobacco. As low as 10.15% of the population
      engaged in regular physical activity. 55.46% of the subjects were vegetarian.
      22.65% suffered from disturbed sleep pattern. Smoking showed statistically
      significant association with hypertension and respiratory tract diseases.
      Physical activity showed association with obesity and disorder of locomotion.
      Behavior and lifestyle modification in the form of primordial prevention and
      counseling of the high risk groups should be carried to improve the quality of
      life of the aged.

PMID- 12508635
TI  - Iron hydroxide polymaltose--cause of persistent iron deficiency anemia at
      delivery.
AB  - Ironhydroxide polymaltose (IPC) preparations were used to treat four pregnant
      women with iron deficiency anemia. Despite patient compliance for sufficient
      length of time, hemoglobin failed to rise. By the time this was noticed,
      pregnancy was well advanced and delivery was only few weeks away. Patients were
      switched over to ferrous fumarate/succinate/parenteral iron. Although hemoglobin
      increased, women were still iron deficient at the time of delivery. Besides
      exposing women to hazards of iron deficiency at the time of delivery, their new
      borns are exposed to the risks intrauterine growth retardation and its
      consequences in childhood and later life. It would be advisable to avoid the use
      IPC preparations in patients with iron deficiency anemia, especially pregnant
      women.

PMID- 12508636
TI  - Rabies.

PMID- 12508637
TI  - Global alliance for vaccines and immunization (GAVI).

PMID- 12508638
TI  - The International Vaccine Institute.

PMID- 12508639
TI  - [Combination therapy of experimental murine hepatoma with mIL-12 gene and MHC I
      gene mediated by liposome].
AB  - BACKGROUND & OBJECTIVE: Interleukin-12 gene and MHC I gene have been used in gene
      therapy for cancer individually. To explore the synergistic antitumor effects of
      these two genes, the therapeutic effects of mIL-12 gene combined with MHC I
      (mouse H-2K) gene mediated by cationic liposome for experimental murine hepatoma
      were investigated. METHODS: Balb/C mouse liver cancer MM45T. Li cells were
      transfected with pcDNA3/mIL-12, pcDNA3/H-2Kb(H-2K of C57BL/6 mouse), and
      pcDNA3/GFP (reporter gene) mediated by lipofectAMINE 2000(LF 2000). The
      expressions of foreign genes in transfected cells were detected. Balb/C mice were
      inoculated subcutaneously with pcDNA3/mIL-12 and pcDNA3/H-2Kb transfected MM45T.
      Li. The tumorigenesis of the inoculated cells was detected. After intratumoral
      injection with LF2000-plasmid DNA complexes, the growth of murine tumor and the
      survival time of the tumor bearing mice were observated. RESULTS: The optimal
      ratio of LF2000: DNA is 3:1(microgram: microgram). The transfection efficiency
      reached to 30%. RT-PCR result showed the specific amplified fragments of the mIL
      12 cDNA and H-2Kb cDNA in the transfected cells. Western blot analysis showed the
      expression of H-2Kb protein at 57 kDa. ELISA assay showed that the secretory mIL
      12 was 48 ng/ml/10(6) cells. The tumorigenesis was decreased for transfected
      MM45T. Li cells with pcDNA3/mIL-12 and pcDNA3/H-2Kb. FACS assay showed that the
      numbers of CD3+, CD4+, and CD8+ cells from murine spleen were increased more in
      therapeutic group than in control group. The tumors grow slowly. The mIL-12 gene
      combined with H-2Kb gene has stronger antitumor effect for mouse liver cancer
      than single gene. CONCLUSION: The combination therapy with mIL-12 gene and MHC I
      gene mediated by LF-2000 have the positive synergistic antitumor effect for
      experimental murine hepatoma.

PMID- 12508640
TI  - [Mutation analysis of KLF6 gene in human nasopharyngeal carcinomas].
AB  - BACKGROUND & OBJECTIVE: Nasopharyngeal carcinoma (NPC) is one of the most common
      cancers in South China and Southeast Asia. The etiological factor is believed to
      be the interaction between genetic susceptibility, EBV infection and
      environmental factors, involved in the multi-step process of carcinogenesis and
      development of NPC. However, the molecular pathology of NPC is unclear yet.
      Kruppel-like factor 6(KLF6) is a ubiquitously expressed nuclear transcription
      factor, which is deleted and/or mutated with high frequency in a subset of
      prostate cancer. This study was designed to investigate KLF6 mutation in NPC
      tumors and NPC cell lines. METHODS: Genomic DNAs from 19 NPC tumor biospies and 3
      NPC cell lines were used in mutation detection of KLF6 coding region and splice
      sites by PCR-sequencing. 100 chromosomes from 50 random healthy individuals were
      used as control. RESULTS: In 3 of 19 NPC tissues, 3 different mutations
      (Glu75Val, Ser136Arg, Arg243 Lys) in KLF6 gene were found by PCR-sequencing. None
      of the 3 mutations were detected in the 50 random healthy individuals.
      CONCLUSION: KLF6 gene may be involved in carcinogenesis of sporadic NPC.

PMID- 12508641
TI  - [Effects of retinoid Ro 40-8757 on human cancer cell lines in vitro].
AB  - BACKGROUND & OBJECTIVES: The retinoids are potent anti-tumor drugs affecting
      cellular proliferation and inducing cell differetiation or apoptosis. This study
      was designed to investigate the anti-proliferative effect of a new-developed
      retinoid, Ro 40-8757, on cell structure, cell cycle and cell cycle proteins of
      four human cancer cell lines in vitro in order to reveal its probable mechanism.
      METHODS: MTT assay was used to determine the anti-proliferative effects of Ro 40
      8757 on human cancer cell lines CCL-187, CCL-229, JF-305, and ASPC-1. Microscopy
      was used to observe CCL-187 morphological changes. Flow cytometry was performed
      to investigate the influence of Ro 40-8757 on cell cycle. Western blot analysis
      was conducted to detect the cell cycle proteins p16, p21, and p27 as to discuss
      the possible mechanism. RESULTS: Ro 40-8757 significantly inhibited the growth of
      the four cancer cell lines in a dose-, time-dependent manner and without any
      signs of cytotoxicity, differentiation, or apoptosis. After treating with Ro 40
      8757, the cell of CCL-187 was arrested at G0/G1 phase. Both p21 and p27 were
      rapidly increasing at the first 12 hours after exposed to the agent, then
      decreasing slowly in the 24, 48 hours, and increasing again in 72 to 144 hours.
      P16 did not express at all either before or after agent treatment. CONCLUSION:
      The results suggest that Ro 40-8757 inhibits the growth of human cancer cell
      lines in vitro by means of cell cycle arrest (mediated by up-regulating cell
      cycle protein P21 and P27) instead of cytotoxic effects, differentiation, or
      apoptosis.

PMID- 12508642
TI  - [Apoptosis and re-expression of p16 gene in the myeloma cell line U266 induced by
      synergy of histone deacetylase inhibitor and demethylating agent].
AB  - BACKGROUND & OBJECTIVE: Histone deacetylation is associated with transcriptional
      activation controlled by DNA methylation. It is important to investigate changes
      of tumor cells treated with agent through two kinds of mechanisms. This study was
      designed to investigate the synergic effect of histone deacetylase inhibitor,
      sodium phenylbutyrate(SPB), and demethylating agent, 5-Aza-2'-deoxycytidine(5-Aza
      CdR), on cell growth and explore the possibility of re-expression of the
      hypermethylated and silenced p16 gene in the myeloma cell line U266. METHODS: The
      cell cycle was analyzed by flow cytometry. Apoptosis was observed by transmission
      electron microscopy, DNA ladder, fluorescence-activated cell sorter (FACS). The
      expression level of p16 was detected by RT-PCR and Western blot analysis.
      RESULTS: The apoptotic rates of U266 cells induced by 5-Aza-CdR(1 mumol/L), SPB(1
      mmol/L) alone and combination of 5-Aza-CdR and SPB were 15.09%, 89.19%, and
      85.18%, respectively. The G1 phase was arrested and sub-G1 phase(50%) was induced
      by combination of 5-Aza-CdR and SPB. There was no G1 phase arrested when SPB or 5
      Aza-CdR was used alone. The proportion of cells in G2 phase was increased with
      SPB alone. SPB was not able to induce the expression of p16. The expression level
      of p16 was induced with 5-Aza-CdR. The expression level of both mRNA and protein
      of p16 was increased significantly by synergy of SPB and 5-Aza-CdR. CONCLUSIONS:
      p16 gene in U266 cell line could be reactivated markedly with synergy of 5-Aza
      CdR and SPB with cell cycle arresting in G1 phase. Meanwhile, the cell cycle
      phase occurring apoptosis that induced by combination of 5-Aza-CdR with SPB is
      different from that induced by each alone.

PMID- 12508643
TI  - [Specific anti-tumor effect of immune competent cell induced by HSP-70 of HeLa
      cells in vitro].
AB  - BACKGROUND & OBJECTIVE: Recent studies indicated that heat shock proteins (HSPs)
      are associated with antigenic peptides and participate in the antitumor T cell
      response in animals. This study was designed to investigate the mechanism of anti
      tumor effect of immune competent cells (ICC) induced by HSP-70 of HeLa (cervical
      carcinoma) cells in vitro. METHODS: The normal peripheral blood mononuclear
      cells(PBMCs) stimulated with HSP-70 of HeLa cells in vitro. T cell phenotypes
      were analyzed before and after stimulated by PBMCs. HSP-70 primed the immune
      competent cells (ICCs) from PBMCs were tested for cytotoxic activity against HeLa
      cell. RESULTS: CD3+ cell was 85.73 +/- 1.44%, up from 57.68 +/- 1.46% before the
      amplification(P < 0.002). CD8+ cell was 48.06 +/- 1.66%, up from 23.56 +/- 1.86%
      before the amplification(P < 0.002). The ICCs induced by HSP-70 were shown
      significant cytotoxic activity (82.69 +/- 1.97%, 62.11 +/- 1.61%) against HeLa
      cells and cervical carcinoma cells, and the cytotoxic activity (31.05 +/- 2.09%)
      of the ICC against HeLa cells could be blocked by anti-HSP-70 antibody.
      CONCLUSION: The ICC can be induced selectively by PBMCs with HSP-70 of HeLa
      cells, and has specific cytotoxic activity against HeLa cell.

PMID- 12508644
TI  - [Screening of novel genes differentially expressed in human renal cell carcinoma
      by suppression subtractive hybridization].
AB  - BACKGROUND AND OBJECTIVE: Identifying the differentially expressed genes in renal
      cell carcinoma (RCC) contributes to the elucidation of its genetic basis.
      However, the above knowledge has not yet been fully understood. The aims of this
      experiment were to screen novel genes differentially expressed in RCC tissues by
      suppression subtractive hybridization (SSH) and clone RCC-specific related genes.
      METHODS: To construct SSH library of RCC by using the mRNA from RCC tissues and
      matched normal kidney tissues as tester and driver, respectively. Partial
      positive clones in the library were selected randomly and sequenced, then analyze
      the sequences with the BLAST software. To confirm the location of the fragments
      of interest in human chromosome through comparing their sequences with the human
      genome draft. mRNA levels of the novel genes in RCC and matched normal kidney
      tissues were determined by Northern blot and semi-quantitative RT-PCR analysis.
      RESULTS: The SSH library contained 414 positive clones. Random analysis of 280
      clones with enzyme restriction showed that 265 clones contained cDNA fragments
      distributed mainly between 300-900bp. Among 80 arbitrary clones with were derived
      from above 265 clones and sequenced, No. 28, 158, 170, and 249 clones are
      previously unknown genes and located in human chromosome 21q22, 4p15.3, 9q34, and
      22q11.2 by electronic mapping, respectively. The consequence of semi-quantitative
      RT-PCR demonstrated that mRNA levels of the two novel genes were overexpressed in
      RCC compared to matched normal tissues by more than 2-6 folds. Northern blot
      analysis confirmed the above results. CONCLUSIONS: SSH is a reliable strategy for
      screening novel genes differentially expressed in RCC. The novel gene fragments
      can be used to clone their full length and further to study their functions.

PMID- 12508645
TI  - [Telomerase gene antisense oligodeoxynucleotide down-regulates telomerase
      activity in HL-60 cells].
AB  - BACKGROUND & OBJECTIVE: Human telomerase reverse transcriptase (hTERT) is a
      limiting component for telomerase activity. Telomerase inhibitor targeting
      telomerase RNA could arrest growth of tumor cells. This study was designed to
      explore the effect of hTERT gene antisense phosphorothioate oligodeoxynucleotide
      (ASODN) on telomerase activity in HL-60 cells. METHODS: Telomeric repeat
      amplification protocol was used to determine telomerase activity. The expression
      levels of hTERT mRNA and protein were assayed by reverse transcriptase polymerase
      chain reaction (RT-PCR) and immunofluorescence using fluorescence isothiocyanate
      label respectively. RESULTS: RT-PCR and immunofluorescence assay showed that the
      expression levels of hTERT mRNA and protein from HL-60 cells decreased with time
      after hTERT ASODN treatment. There was no difference in hTERT mRNA and protein
      levels between control and SODN-treated cells. Telomerase activity decreased when
      HL-60 cells were treated with ASODN for 48 h. Telomerase activity of HL-60 cells
      was significantly inhibited when treated with ASODN for 72h. There was no
      difference in telomerase activity levels between control and hTERT SODN-treated
      cells. CONCLUSION: Telomerase activity could be down-regulated by hTERT ASODN in
      HL-60 cells.

PMID- 12508646
TI  - [Relationship between p27 expression and prognosis of colorectal carcinoma].
AB  - BACKGROUND & OBJECTIVE: It has been reported that p27 is associated with
      prognosis of some tumor. This study was designed to investigate the relationship
      between expression of p27 and prognosis of colorectal carcinoma. METHODS: The
      expression of p27 in 82 colorectal carcinoma specimens was detected by
      immunohistochemical method. The relationship between the expression of p27 and
      clinicopathological characteristics or survival time was analyzed by chi 2 test
      or log rank test, respectively, while univariate and multivariate prognostic
      analyses were performed by using Cox regression model. RESULTS: High p27
      expression rate in colorectal carcinoma was 53.66% (44/82), while low expression
      rate was 46.34% (38/82). Low p27 expression in colorectal carcinoma was
      significantly associated with late Dukes stage, high incidence of lymph
      metastasis, and distant metastasis. Long rank test showed that the p27 expression
      was positively correlated to survival time and Cox regression indicated that the
      p27 was an prognostic marker of colorectal carcinoma. CONCLUSION: Low p27
      expression in colorectal carcinoma was significantly associated with late Dukes
      stage, high incidence of lymph metastasis, and distant metastasis, poor
      prognosis, and short survival time. p27 is an prognostic marker of colorectal
      carcinoma.

PMID- 12508647
TI  - [Effect of preoperative intra-arterial chemotherapy on apoptosis and p53
      expression of gastric cancer].
AB  - BACKGROUND & OBJECTIVE: Regional chemotherapy is charactized by a high drug
      concentration in tumor tissues and slight side-effects. Some significant
      histopathological changes were observed in the patients with gastric carcinoma
      treated by selective intra-arterial infusion chemotherapy before operation. The
      aim of this study was to investigate the effect of preoperative intra-arterial
      chemotherapy on apoptosis and p53 expression in human gastric cancer and its
      clinical significance. METHODS: The apoptosis was examined by terminal uridine
      deoxynucleotide nick end labeling (TUNEL) and the expression of p53 was detected
      with immunohistochemistry in 33 patients with gastric carcinoma pre- and post
      chemotherapy respectively. RESULTS: Apoptosis index(AI) was significantly higher
      in the post-chemotherapeutic patients than in the pre-chemotherapeutic ones
      (19.29 +/- 6.48 versus 9.24 +/- 5.03, P < 0.01). In contrast, the positive
      expression rate of p53 was significantly lower, in the post-chemotherapeutic
      patients, than in the pre-chemotherapeutic ones(30.30% versus 54.55%, P < 0.05).
      In the post-chemotherapeutic patients, the droped group of p53 expression were
      strongly associated with a better clinical response(P < 0.05). CONCLUSIONS:
      Preoperative intra-arterial chemotherapy could enhance the apoptosis of gastric
      cancer cell, decrease the level of p53 expression and keep the patients for a
      longer survival.

PMID- 12508648
TI  - [Factoral analysis related to primary recurrence of laryngeal squamous cell
      carcinomas after treatment].
AB  - BACKGROUND & OBJECTIVE: This study was designed to investigate the factors
      associated with the primary recurrence in laryngeal squamous cell carcinomas
      after treatment. METHODS: A total of 166 cases of laryngeal squamous cell
      carcinomas hospitalized in Cancer Center of Sun Yat-sen University from 1990 to
      1995 were reviewed retrospectively. It was considered primary recurrence that
      pathologically confirmed recurrence after 6 months of follow-up. The correlative
      factors which included age, pathological differentiation, diseased site, stage,
      treatment modality, surgical procedures, surgical margin, and radiotherapy with
      primary recurrence were investigated. RESULTS: The primary recurrence in this
      group after treatment was 16.3% (27/166). The primary recurrence rates in
      different treatment modalities of definitive radiotherapy, definitive surgery,
      and combined management were 50%, 8.9%, and 14.1%, respectively, which had
      statistical significance (P < 0.05). The primary recurrence rates in surgical and
      non-surgical(radiotherapy and radiochemotherapy) treatment were 11.3% and 44%,
      respectively, which had statistical significance(P < 0.05). The comparison of T
      stage in different treatment modalities showed definitive radiotherapy had
      earlier T stage than definitive surgery and combined therapy(P < 0.05). The
      primary recurrence rates in positive and negative surgical margin were 34.8% and
      6.1%, respectively, which had statistical significance (P < 0.05). CONCLUSIONS:
      The treatment of primary site influences directly the primary relapse. Surgical
      treatment has better primary control than non-surgical treatment. Definitive
      radiotherapy has more probability of primary recurrence. The surgical clearance
      of the primary site influences directly the primary control.

PMID- 12508649
TI  - [Preliminary analysis on the gene expression profiles of different types of
      gliomas with cDNA array].
AB  - BACKGROUND & OBJECTIVE: There is great signification to classify the molecular
      pathogenesis of gliomas. Gene chip is able to profile the gene expression of
      tumors, which may become a new method for studying molecular pathology of tumors.
      The cDNA was used in order to detect the differences in gene expression profiles
      of different types of gliomas. METHODS: cDNA probes tagged with 32P were
      converted from total RNA extracted from 4 samples of 3 different pathological
      types, including oligodendrogliomas, anaplastic astrocytomas and ependymomas, and
      one sample of normal human brain tissue as well, which were then hybridized to
      the Atlas array. After autoradiography, the gene expression profiles were
      analyzed with the special software and by the cluster analysis. RESULTS: As
      compared to the normal brain tissue, the number of differential expressed genes
      in these tumor samples ranging from 11 to 118 was found. These 4 samples could be
      divided into 3 kinds of types when 107 differential expressed genes were selected
      to be as the cluster analysis index. This result was in accordance with the
      neuropathological diagnosis. CONCLUSION: cDNA array is able to profile gene
      expression in different types of gliomas. Combined with the bioinformational
      method, we may further obtain useful information about molecular pathology of
      gliomas.

PMID- 12508650
TI  - [Experimental study of combination therapy against human glioma xenograft by
      differentiation-inducing agent and cytotoxic chemotherapeutic drug].
AB  - BACKGROUND & OBJECTIVE: Cytotoxic agent remains the main chemotherapeutic drug
      for glioma, although it has many limitations. It is not known whether
      differentiation-inducing agent can enhance antitumor efficiency of cytotoxic
      agent. This study was designed to investigate anti-tumor effects of
      differentiation-inducing agent in combination with cytotoxic chemotherapeutic
      drug against glioma. METHODS: Poorly-differentiated human brain glioma
      xenografted nude mice were treated with carmustine(1, 3-bis-(2-chloroethyl)-1
      nitrosourea, BCNU) and sodium phenylbutyrate (SPB). The therapeutic effects were
      determined by measuring of tumor size, pathological changes, different phases of
      cell cycle of tumor cell proliferation, expression of differentiation antigen,
      and tumor cell apoptosis. RESULTS: The therapeutic effects of SPB plus BCNU group
      were much better than that of SPB or BCNU group alone, which were proved by lower
      growth rate of the tumor, cellularity decreasing, appearance of astroid-like
      polyglonal cells, G0/G1 ratio increasing, upregulation of GFAP expression.
      CONCLUSION: Combined application of SPB and BCNU can obviously inhibit
      proliferation of glioma, and promote differentiation of tumor cells.

PMID- 12508651
TI  - [Molecular mechanism of antisense glycosyltransferase oligonucleotide inhibiting
      human gliomas cell line SWO-38].
AB  - BACKGROUND & OBJECTIVE: It was reported that Globo series glycoshingolipids have
      relationship to many human cancers, and alpha 1, 4-galactosyltransferase(alpha 1,
      4Gal-T) oligonucleotide is the specific glycosyltransferase for the synthesis of
      Globo series glycoshingolipids. This study was designed to evaluate the effects
      of antisense alpha 1, 4Gal-T oligonucleotide on human gliomas cell line SWO-38.
      MATERIALS & METHODS: SWO-38 glioma cells were reacted with 10 mumol/L antisense
      alpha 1, 4Gal-T oligonucleotide for 72 hours by means of lipofectin transfection.
      The growth inhibition was detected by colony-forming unit assay. DNA
      fragmentation was examined by flow cytometric analysis(FCM) and agarose gel
      eletrophoresis. The expressions of fas, p53, bax, and bcl-2 protein were
      determined by flow cytometric analysis (FCM). RESULTS: Antisense alpha 1, 4Gal-T
      oligonucleotide signifantly inhibited cell growth (P < 0.01), induced the
      apoptosis (P < 0.05), downregulated expression of bcl-2 protein (P < 0.01) and
      upregulated expressions of fas and bax protein (P < 0.01), but did not influence
      p53 expression in glioma cell line SWO-38. CONCLUSIONS: Antisense alpha 1, 4Gal-T
      oligonucleotide can significantly inhibit proliferation and induce apoptosis in
      human gliomas cell line SWO-38, which maybe due to the interactions of fas, bax,
      and bcl-2.

PMID- 12508653
TI  - [Several monomes from Tripterygium wilfordii inhibit proliferation of glioma
      cells in vitro].
AB  - BACKGROUND AND OBJECTIVE: Researches indicated that Tripterygium wilfordii
      possess antitumor activity. The current study was designed to investigate
      inhibitive effect of several monomes of Tripterygium wilfordii on the
      proliferation of glioma cells. METHODS: The effect of three monomes from
      Tripterygium wilfordii on the proliferation of glioma cell lines SHG44, C6, and
      U251 in vitro was examined by using MTT assay. Immunohistochemistry was used to
      examine the expression of Bax, Bcl-2 after treatment of triptolide and celastrol.
      RESULT: The proliferation of glioma cells was remarkably inhibited by triptolide
      and celastrol. They both increased expression of Bax and decreased expression of
      Bcl-2 in the SHG44 cells. CONCLUSION: Triptolide and celastrol inhibit the
      proliferation of glioma cells in vitro, which was associated with promoting the
      expression of Bax and inhibiting the expression of Bcl-2 and accelerating cell
      apotosis.

PMID- 12508652
TI  - Trichostatin A inhibits proliferation and induces expression of p21WAF and p27 in
      human brain tumor cell lines.
AB  - BACKGROUND AND OBJECTIVE: The histone deacetylase inhibitor, trichostatin A(TSA),
      was shown to induce apoptosis in transformed cells at submicromolar
      concentrations. However, the effect of TSA on brain tumor cells is still unknown.
      This study was designed to investigate whether TSA posses antitumor activity and
      if any, its mechanism. MATERIALS AND METHODS: A p53 mutant human glioma cell line
      T98G and a p53 wild type human neuroblastoma cell line SKNSH were exposed to TSA.
      Cell proliferation was assessed by sulforhodamine B (SRB) cytotoxicity assay.
      Apoptosis was quantified by flow cytometry and confirmed by apoptotic ladder
      formation. Expression patterns of accumulation of highly acetylated histone H3,
      H4; p53 and cell cycle-associated p21waf, p27 which were induced by TSA were
      determined by using Western blot analysis. RESULTS: TSA inhibited the
      proliferation of brain tumor cell lines at nanomolar concentrations and induced
      accumulation of highly acetylased histone moleculars. Treatment with TSA at 0.33
      microM for 24 h significantly induced cell apoptosis. In addition to the
      suppression of cell growth, the up regulation of p21waf and p27 expression was
      observed within 48 h after the treatment. p21 protein levels were increased at
      early time points and reached maximal levels at 8 h, while p27 protein levels
      were increased after 8 h. However, there was no significant changes of acetylased
      p53 and endogenous p53 protein levels were observed. CONCLUSION: TSA may inhibit
      brain tumor cell growth in vitro, which is otherwise particularly resistant to
      chemotherapy. TSA acts as an anti-tumor agent could be through co-operation
      between p21 and p27 in growth inhibition, irrespective of endogenous p53 status.

PMID- 12508654
TI  - [Endothelin-1 expression and quantitative analysis in astrocytomas].
AB  - BACKGROUND & OBJECTIVE: It is demonstrated that endothelin-1 (ET-1) is
      synthesized by and released from certain malignant tumor cells, and it plays an
      important role in growth and development of tumor. This study was designed to
      investigate the expression of ET-1 in astrocytomas and the relationship between
      the ET-1 quantity and the grades of astrocytomas. METHOD: ET-1 expression was
      determined in 70 astrocytoma specimens using Streptavidin-Peroxidase method and
      image analysis technology. RESULTS: The ET-1 expressed in all of astrocytomas,
      and the ET-1 expression was mainly located in the cytoplasm. The positive rates
      of ET-1 in grade IV and III astrocytomas (86.67% and 93.33%) were significantly
      higher than that in grade II, I and normal astrocytes(75.00%, 66.67%, and 37.50%)
      (P < 0.05). The results of image analysis on astrocytoma (grade IV, III, II, I
      and normal control: 0.1875 +/- 0.0227, 0.1516 +/- 0.0134, 0.1215 +/- 0.0116,
      0.1048 +/- 0.0143, and 0.0717 +/- 0.0074, respectively) showed that the lower
      differentiation of astrocytoma, the higher ET-1 expression (P < 0.01). The
      expression of ET-1 was significantly correleted with the tumor grading (r =
      0.863, P < 0.01). CONCLUSION: The ET-1 quantitative analysis may be used as a
      monitoring index of astrocytoma growing.

PMID- 12508655
TI  - [Inhibition of human glioma cell growth by a soluble recombinant human CD40
      ligand].
AB  - BACKGROUND & OBJECTIVE: CD40 presents on B cells, monocytes, dendritic cells, and
      endothelial cells, as well as a variety of neoplastic cell types, including
      carcinomas. CD40 stimulated by its antibody or CD40 ligand previously had been
      demonstrated to induce activation-induced cell death in ovarian carcinoma cell
      lines, colon carcinoma cell lines, breast carcinoma cell lines, and lung
      carcinoma cell lines and to inhibit their growth in vivo. This study was designed
      to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on
      human glioma cell lines. METHODS: The specimens of human glioma were examined for
      CD40 expression by immunohistochemistry. The human glioma cell lines were
      examined for CD40 expression by flow cytometry. The cell lines were incubated
      with srhCD40L for 24h and 72h, then the markers of proliferation and apoptosis of
      these cells were determined, respectively. RESULTS: CD40 expression could be
      detected in 7/23 human glioma specimens and 1/3 cell line. The srhCD40L inhibited
      the proliferation of CD40+ human glioma cell line. The viability of these cells
      was decreased from 98% to 87%. The apoptosis and death of these cells were
      increased by 17.4%. CONCLUSIONS: CD40 stimulated by its ligand directly inhibits
      human glioma cell growth in vitro. These results suggest that srhCD40L may be of
      clinic use to inhibit glioma growth.

PMID- 12508656
TI  - [Clinicopathological study of primary meningeal hemangiopericytoma].
AB  - BACKGROUND AND OBJECTIVES: Meningeal hemangiopericytoma is an uncommon tumor.
      This study was designed to investigate the clinicopathological and biology
      behavior of primary meningeal hemangiopericytoma. METHODS: Clinical data,
      combined with histopathology and immunohistochemistry of 20 cases of meningeal
      hemangiopericytoma were reviewed, in which 4 specimens were examined with
      electron microscope. RESULTS: The average age of patients with primary meningeal
      hemangiopericytoma was 42.4 year-old (21-69 years). The ratio of male to female
      was 1.2: 1. Most of the patients went to hospital for the symptoms of central
      nervous system such as headache. The tumor could occur on any locus of the
      cranial or spinal dura. Grossly, many of the tumors had capsule, whose testure
      were tenacious, and part of them looks like fish meat. Histopathologically, the
      small vascular spaces in the tumor were rich, the typical antler-liked vessel
      could be found, the short-spindle tumor cells were around the vessel, and
      distributed by radiation-shape. The tumor cells were pleomorphic and atypical,
      and could be found mitotic activity. Staining of argyrophilic fiber: the
      argyrophilic fiber surrounded single tumor cell, and distributed by radiation
      shape around vessel. Immunohistochemistry showed negative for S-100 protein, F
      VIII, EMA, GFAP and CD34, while Vim was positive. Electron microscopically, the
      rich bundles of 10nm long intermediate filaments could be found in tumor cells.
      The exobasallamina, of cells were evidenced, and distributed around single cell.
      Follow-up, 8 of 17 cases were relapsed (47.1%). CONCLUSION: Meningeal
      hemangiopericytoma is a low-malignant tumor original from meningeal mesenchymal
      tissue. The features of histopathology, immunphenotype and ultrastructure are
      similar to hemangiopericytoma of the soft tissue.

PMID- 12508657
TI  - [Preliminary study of chromosome aberrations in pituitary adenoma].
AB  - BACKGROUND & OBJECTIVE: Pituitary adenoma is one of the most common intracranial
      benign tumor. This study was designed to seek the most suitable method for
      cytogenetic study of pituitary adenoma(PA), and then to analyze the genetic
      change of PA cell. METHODS: Twenty-five samples of primary PA were examined by R
      banding through direct preparation(DP) and short-term culture(STC) to analyze
      genomic alterations. RESULTS: A karyotype of 17 samples was identified in 25 PAs
      by using the DP, whereas there was a karyotype of 21 samples by using the STC. An
      abnormal clonal karyotype was observed in 11 samples processed by the DP, however
      only 3 of 25 samples when processed by the STC. The common chromosomal
      alterations included gains of chromosomes X(6/25), 7(4/25), 8(2/25), 5(2/25) as
      well as losses of chromosomes 11(5/25), 9(4/25), 13(3/25), and the latter was
      observed predominantly in invasive PAs. CONCLUSIONS: DP is one of the most
      suitable methods for the cytogenetic study of PA. There were multiple regions of
      chromosomes with copy number changes in PA including gains of chromosomes X, 7,
      8, and losses of chromosomes 11, 9, 13. However, structural chromosome
      aberrations are not common. The loss of chromosome and the abnormality of
      structure may have some correlation with the biologic behavior of PA.

PMID- 12508658
TI  - [Role of matrix metalloproteinases-9, 2 and their inhibitor-TIMP-1, 2 in invasive
      pituitary adenomas biological behavior].
AB  - BACKGROUND & OBJECTIVE: Usually pituitary adenomas are histological benign and
      grow slowly, but a proportion of them will become locally aggressive, and develop
      into invasive pituitary adenomas. The reasons for these differences in tumor
      behavior are poorly understood. Pituitary adenomas are abounding blood vessels.
      Angiogenesis and tumor invasion both require degradation of the extracellular
      matrix components to allow cell migration. The matrix metalloproteinases (MMPs)
      and their nature inhibitors-the tissue inhibitors of metalloproteinases (TIMPs)
      may play a central role in these processes. The aggressive mechanism of pituitary
      adenomas was studied through investigating the expression of MMP-9, MMP-2, TIMP
      1, and TIMP-2 in both invasive and non-invasive adenomas. METHODS: Sixty-one
      surgical removed pituitary adenomas (forty-nine cases invasive and twelve non
      invasive adenomas) were investigated. Immunohistochemistry staining (SP method)
      was used to detect the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in two
      groups. The results were treated with semi-quantitative method and analyzed by
      using non-parameter rank sum test. RESULTS: Immunohistochemical staining of tumor
      cells for MMP-9, TIMP-1, MMP-2, and TIMP-2 were noted 95.9% (47/49), 57.1%
      (28/49), 75.5% (37/49) and 89.8% (44/49) in invasive adenomas, and 100% (12/12),
      91.7% (11/12), 66.7% (8/12), and 91.7% (11/12) in non-invasive adenomas,
      respectively. Invasive tumors were significantly less expressing TIMP-1 and TIMP
      2 (P < 0.05). There was no significant difference for MMP-9 or MMP-2 between
      invasive and non-invasive groups (P > 0.05). CONCLUSIONS: TIMP-1 and TIMP-2 may
      play a key role in invasive pituitary adenomas to biological behavior.

PMID- 12508659
TI  - [Microneurosurgical treatment for gliomas located in lateral fissure area].
AB  - BACKGROUND & OBJECTIVE: It has been generally recognized that extensive resection
      for gliomas is directly associated with better prognosis of the patients.
      However, some tumors in functional area are not easy to be radically resected and
      neurological deficiency could be resulted by surgery. This study was designed to
      investigate whether gliomas located in lateral fissure area could be radically
      resected without neurological deficiency. METHODS: There were 22 gliomas located
      in lateral fissure area underwent microsurgical resection. The main branches of
      middle cerebral artery were preserved and the patients, if any neurological
      disfunction occurrence, were treated accordingly. RESULTS: All 22 gliomas were
      totally or subtotally resected using microneurosurgical technique. In 7 cases the
      reserved functional vessels which pass through tumor mass, look like "bridge"
      after tumor resection. Six patients resulted in motor disfunction following
      surgery, in which 5 cases were recovered and KPS reached 70 after 6 months.
      CONCLUSION: Gliomas located in lateral fissure area could be radically resected
      under microscope resulting no neurological deficiency, if any, will recover.

PMID- 12508660
TI  - [Clinical study on the removal of sellar region tumors by pterional approach
      (report of 119 cases)].
AB  - BACKGROUND & OBJECTIVE: Sellar region tumors are common intracranial tumor. This
      study was designed to investigate the methods of the removal of tumors in sellar
      region by pterional approach. METHODS: A total of 119 cases with sellar region
      tumors were performed operation. Before the operation, the relationships between
      the tumors and their periphery were determined according to CT, MR and the
      cerebral angiography and then the tumors were removed by pterional approach
      microsurgery in 4 different spaces. RESULTS: The number of the patients treated
      with total, subtotal, and partial resection were 72, 36, and 11, respectively;
      with 85 cases significantly improved, 24 getting better, 8 without changes and 2
      dead. Follow-up half a year, 92 cases were survival in the half a year of follow
      up, in which 61 cases were able to work with normal life, 15 could do light work,
      9 could take care of themselves but 6 patients were disabled, and 1 died of heart
      disease. CONCLUSION: Pterional approach can be used to remove many kinds of
      tumors in sellar region and with better exploration, therefore, increase the
      total removal and cure rate of such tumors.

PMID- 12508661
TI  - [Keyhole microsurgery for acoustic neurinomas through suboccipital retrosigmoid
      sinus approach].
AB  - BACKGROUND AND OBJECTIVE: Acoustic neurinomas is one of the most common benign
      tumor in central nervous system, the main treatment is surgical resection. This
      study is to explore keyhole surgery with suboccipital retrosigmoid sinus approach
      for acoustic tumor resection and discuss how to improve the surgical skill and
      effect. METHODS: Thirteen cases of acoustic neurinomas from Sept. 2000 to Dec.
      2001 in our department were operated using keyhole craniotomy technique through
      unilateral modified suboccipital retrosigmoid approach with "[symbol: see text]"
      incision. All patient underwent suboccipital craniotomy in order to maintain
      anatomical replacement, and the tumors (2.0-4.4 cm in diameter) were removed
      under microscope. RESULTS: Tumors were completed resected in 11 cases, subtotally
      removed in 2 cases. Eleven patients had obtained anatomic preservation of the
      facial nerves. Complete follow-up information was obtained in all patients for a
      period of 3-15 months after operation. House-Brackmann Score in 8 case were Grade
      I-II, 4 cases Grade III-IV, one case Grade V. Grades I and II facial nerve
      function were maintained in 61.5% of cases, measurable hearing was preserved in
      53.8% of cases(7 cases), and 38.5% of cases maintained serviceable hearing. No
      severe permanent operative complications were found and no surgical mortality
      occurred. CONCLUSIONS: Microsurgery with keyhole craniotomy is a safe and
      effective method for treatment of patients with small and medium-size acoustic
      neuromas. The advantages of keyhole suboccipital craniotomy are anatomical
      replacement, less postoperative complications, and beneficial to patient's mental
      health.

PMID- 12508662
TI  - [Analysis of prognostic factors for 63 patients with brain metastasis from lung
      cancer after radiochemotherapy].
AB  - BACKGROUND & OBJECTIVE: Brain metastasis is often found in the patients with lung
      cancer. Radiotherapy is regular and effective method, and it aims at palliating
      symptoms and prolonging survival time. However, now there are different
      viewpoints on protocols of radiotherapy and prognostic factors. A retrospective
      analysis was used to evaluate the results of treatment for 63 cases with brain
      metastasis from lung cancer and explore the prognostic factors. MATERIALS AND
      METHODS: Sixty-three patients of brain metastasis from lung cancer from Jan. 1994
      to Dec. 2000 were studied retrospectively. All of them have received radiotherapy
      (RT) and 42 cases received combined chemotherapy. The median dose of radiotherapy
      was 40Gy(24-62.4 Gy). Mean survival times from two factors were compared by t
      test and the cumulative survival rate was analyzed by Kaplan-Meier estimates, and
      the influencing factors were screened by Cox proportional hazard model. RESULTS:
      The mean survival times were 9.5 months in the radiochemotherapy group and 6.3
      months in radiotherapy alone group, 9.3 months in good response group and 5.0
      months in the poor response group (P = 0.043), 10.8 months in the > or = 50 Gy
      group and 6.7 months in the < 50 Gy group(P = 0.028), and 10 months in > or = 1.8
      Gy fraction group and 4.8 months in the < 1.8 Gy fraction group (P = 0.015).
      Survival analysis results suggested that the patients with combined chemotherapy
      and good response have better prognosis. CONCLUSIONS: Combined chemotherapy and
      efficacy at the end of treatment are independent prognosis factors of brain
      metastasis from lung cancer.

PMID- 12508663
TI  - [Efficacy of permanent interstitial implantation of 125I seeds for solitary brain
      metastasis from non-small cell lung carcinoma].
AB  - BACKGROUND & OBJECTIVE: Some studies have already showed that whole brain
      irradiation (WBI) could cause radiation brain damage. It is necessary to explore
      a novel treatment modality to replace whole brain irradiation without influencing
      the therapeutic efficacy. The purpose of this study was to assess the therapeutic
      efficacy and radiation brain damage of permanent interstitial implantation of
      125I seeds following tumor resection for solitary brain metastasis from non-small
      cell lung carcinoma (NSCLC). METHODS: Sixty-seven patients with solitary brain
      metastasis from non-small cell lung carcinoma were randomly assigned into two
      groups: Thirty-two cases(47.8%) were treated with resection and permanent
      interstitial implantation of 125I seeds(I), and 35(52.2%) received whole brain
      irradiation and local-small-field radiation (C). All patients were biopsy
      verified non-small cell lung carcinoma, including 42 squamous cell carcinomas and
      25 adenocarcinomas. They all were solitary brain metastasis from non-small cell
      lung carcinoma diagnosed by CT or MRI. After resection of solitary brain
      metastasis, different numbers of 125I seeds were implanted according to some
      parameters in group I. In group C, 35 patients received whole brain irradiation
      to a total dose of 30-39 Gy/3-4 weeks, 2-3 Gy/fraction, 5 fractions/week followed
      by a boost of 15-25 Gy/2-3 weeks through local-small fields. RESULTS: The local
      control rate, the recurrent rate, and the median recurrent time were 96.9%,
      15.6%, and 9 months in group I, and 82.9%, 17.1%, and 7 months in group C,
      respectively. The differences were no significant (P > 0.05). The median survival
      time, the 1-year survival rate, and the 1-year mortalities were 12 months, 40.6%,
      and 28.1% in group I, and 9 months, 31.4%, and 37.1% in group C, respectively.
      The differences were significant(P < 0.05). Acute irradiation response and
      radiation brain damage were markedly milder in group I than in group C.
      CONCLUSIONS: The results from this study show that resection and permanent
      interstitial implantation of 125I seeds for solitary brain metastasis from non
      small cell lung carcinoma can not only improve the survival rates and decrease
      the mortalities, but also reduce radiation brain damage to improve the life
      quality. It is a good and effective modality, especially for younger patients.
      However, further study for long-term effect is needed.

PMID- 12508664
TI  - [Prognostic factors for deep situated malignant gliomas treated with linac
      radiosurgery].
AB  - BACKGROUND & OBJECTIVE: Though radiosurgery has been used for more than 10 years,
      the value of radiosurgery for malignant glioma has not been clarified. This paper
      was designed to investigate efficacy of radiosurgery to malignant glioma by
      analyzing the prognostic factors affecting prognosis of malignant gliomas treated
      with linac radiosurgery. METHODS: Fifty-eight patients with deep situated
      malignant gliomas, 28 anaplastic astrocytomas(AA) and 30 glioblastomas (GBM),
      aged from 7 to 70 years, were analyzed. The mean volume of tumor was 12.08 cm3,
      and mean prescription dose for linac radiosurgery was 19.42 Gy. The results were
      analyzed with Kaplan-Meier curve and Cox regression. RESULTS: There were 44.8% of
      the tumors shrank. Median tumor local control interval was 10 months(15 months
      for AA and 9 months for GBM). Tumor local control probability was 37.9% for 1
      year and 10.3% for 2 years. Median survival was 22.5 months for AA and 13 months
      for GBM and 15 months for all patients. The survival probability was 79.3% at 1
      year and 20.6% at 2 years. Isocenter numbers and tumor volume were the prognostic
      factors for tumor control, but conformity index was prognostic factor for
      survival as determined by Cox regression analysis. Considered of pathology, only
      isocenter number and target volume significantly affected the tumor control
      interval. Complication appeared in 44.8% of the patients and the median interval
      of complication onset was 8 months. Symptomatic cerebral edema was observed in
      31.0% of the patients. CONCLUSION: Linac radiosurgery can effectively improve
      tumor local control and elongate survival for the patients with deep situated
      malignant gliomas. Tumor volume is the prognostic factor for tumor control, while
      conformity index is prognostic factor for survival.

PMID- 12508665
TI  - [Analysis of 68 patients with pituitary adenoma treated by radiotherapy].
AB  - BACKGROUND & OBJECTIVES: Pituitary adenoma is a common intracranial tumors, and
      can be treated by surgery or radiotherapy. The aim of this study was to compare
      the result of pituitary adenoma treated by radiotherapy and surgery combined with
      radiotherapy. MATERIALS AND METHODS: From March 1980 to January 1992, 68 patients
      with pituitary adenoma were treated by radiotherapy in our hospital. Sixteen
      patients were treated by radiotherapy alone and 52 patients were treated by
      surgery followed with radiotherapy. The median dose was 49.7 Gy. Fourty-five
      patients were treated with Co60 gamma ray, 10 patients with 8MV X ray and 13
      patients with 18MV X ray. RESULTS: The overall 5- and 10-year survival rates were
      94.1% and 76.8%, respectively. The 5- and 10-year local control rates were 94.1%
      and 88.4%, respectively. The local control rate of patients irradiated more than
      50 Gy (94%) was higher than those under 50 Gy (82%), but without statistic
      significance(P = 0.1796). There were no differences among the different pathology
      and hormone secreting of the tumor, and rays used. Eight patients died from tumor
      recurrence, and 6 patients with hypopituitarism, five of them received more than
      50 Gy (P = 0.0058). CONCLUSION: It is better for patients with pituitary adenoma
      to be irradiated between 45 Gy approximately 50 Gy. Three fields technique should
      be recommended.

PMID- 12508666
TI  - [Influence of DNA polymerases on mutation screening of denaturing high
      performance liquid chromatography].
AB  - BACKGROUND & OBJECTIVE: Recently, a sensitive and accurate technique called
      denaturing high-performance liquid chromatography (DHPLC) has been used in gene
      mutation screening, but several factors, especially DNA polymerase were
      discovered to affect the resolution of DHPLC technique. In order to find one or
      more suitable polymerases for DHPLC analysis, we designed this study to evaluate
      the influence of non-proofreading and proofreading DNA polymerase on mutation
      screening with DHPLC. METHODS: Three fragments which were 268 bp, 317 bp, and 590
      bp in size were chosen for DHPLC analysis. To evaluate the negative influence of
      polymerase on DHPLC resolution, the same fragments were amplified by using 11
      kinds of DNA polymerases [6 brands of Taq, 1 kind of Taq gold and, 4 sorts of
      proofreading DNA polymerase (Pfu and Vent)] and those PCR products were analyzed
      by DHPLC. The chromatographical profile were identified and compared. RESULTS:
      There were two kinds of negative influences on DHPLC analysis chromatography
      profiles. There were no or tiny influences induced by proofreading or Taq gold
      polymerases. CONCLUSIONS: Proofreading DNA polymerase is more suitable for DHPLC
      analysis than Taq polymerase. Especially, Pfu DNA ought to be preferentially
      selected to amplify GC-rich small fragments or other influence-prone fragments
      when mutation is detected by DHPLC analysis.

PMID- 12508667
TI  - Evaluating models of community psychology: social transformation in South Africa.
AB  - Tricket (1996) described community psychology in terms of contexts of diversity
      within a diversity of contexts. As abstract representations of reality, various
      community psychological models provide further diverse contexts through which to
      view the diversity of community psychological reality. The Zululand Community
      Psychology Project is a South African initiative aimed at improving community
      life. This includes treating the violent sequelae of the unjust Apartheid system
      through improving relationships among communities divided in terms of historical,
      colonial, racial, ethnic, political, gender, and other boundaries as well as
      promoting health and social change. The aim of this article is to evaluate the
      applicability of various models of community psychology used in this project. The
      initial quantitative investigation in the Zululand Community Psychology Project
      involved five coresearchers, who evaluated five community psychology models--the
      mental health, social action, organizational, ecological, and phenomenological
      models--in terms of their differential applicability in three partnership
      centers, representing health, education, and business sectors of the local
      community. In all three contexts, the models were rank ordered by a
      representative of each center, an intern community psychologist, and his
      supervisor in terms of the models' respective applicability to the particular
      partnership center concerned. Results indicated significant agreement with regard
      to the differential applicability of the mental health, phenomenological, and
      organizational models in the health, education, and business centers
      respectively, with the social action model being most generally applicable across
      all centers. This led to a further qualitative individual and focus group
      investigation with eight university coresearchers into the experience of social
      transformation with special reference to social changes needed in the South
      African context. These social transformation experiences and perceived changes
      needed are explicated. Finally, there is discussion with regard to the evaluation
      of various models of community psychology in international perspective.

PMID- 12508668
TI  - Predictive genetic testing: mediators and moderators of anxiety.
AB  - Mediators and moderators of anxiety following predictive genetic testing were
      investigated in a cross-sectional study of 208 individuals at risk for familial
      adenomatous polyposis (FAP). Receiving a positive test result was associated with
      increased anxiety. The relationship between test result and anxiety was mediated
      by how threatened individuals felt by their test results. The impact of a
      positive test result was greater for those who felt distressed about FAP in their
      families, perceived FAP to be more serious, and perceived the genetic test to be
      more accurate. The results suggest that assessing, and possibly modifying,
      people's appraisals of the condition and of its impact on the family and of the
      threat of the genetic test may help to reduce subsequent anxiety. This has
      implications for the practice of genetic counseling.

PMID- 12508670
TI  - Physical activity levels of Barbadian youth and comparison to a U.S. sample.
AB  - This is the first study to report on physical activity levels of young people in
      Barbados. The Self-Administered Physical Activity Checklist was administered to
      1,579 children aged 8 to 18 years. The majority of youth (69%) reported at least
      60 min of physical activity on the previous school day. Boys and younger students
      reported greater physical activity than girls and older students (p < .001).
      Participation in physical education was low among primary (30%) and secondary
      (18%) school students, and youth reported the majority of their physical activity
      took place after school (58%). Physical activity levels and patterns were similar
      to those of U.S. youth. Gender and grade differences in physical activity could
      put girls and older youth at higher risk for health problems such as obesity.
      Policy recommendations to support youth physical activity in Barbados include
      mandatory daily physical education and after-school physical activity programs.

PMID- 12508669
TI  - Human response to environmental noise: the role of perceived control.
AB  - Negative impacts of noise exposure on health and performance may result in part
      from "learned helplessness," the syndrome of deficits typically produced by
      exposure to uncontrollable events. People may perceive environmental noise to be
      uncontrollable, and several effects of noise exposure appear to parallel "learned
      helplessness" deficits. In the present socioacoustic survey (N = 1,015),
      perceived control over aircraft noise correlated negatively with some effects of
      noise (though not others). Furthermore, these effects were better predicted by
      perceived control than by noise level. These observational data support the claim
      that "learned helplessness" contributes to the effects of noise exposure.

PMID- 12508671
TI  - [Rare, but important chronic liver diseases].
AB  - The presence of steatosis and inflammatory infiltrate in liver biopsies is
      essential for the diagnosis of non-alcoholic steatohepatitis (NASH). These
      findings are similar to those with alcoholic liver disease. However, in the NASH
      situation alcohol doesn't play an important role. Risk factors for the
      development of NASH are obesity and diabetes. Most of the patients are clinically
      asymptomatic. This means, that a diagnosis of NASH is a diagnosis of exclusion:
      Viral induced, autoimmune, metabolic and toxic liver disease have to be excluded.
      The disease has a benign clinical course. The risk of cirrhosis is low. So far,
      there is no established treatment. Preliminary reports suggest a positive effect
      of weight-loss and ursodeoxycholic acid. Wilson's disease, a copper storage
      disorder, in which biliary copper excretion is reduced, is inherited as an
      autosomal recessive trait. Most patients with Wilson disease become symptomatic
      between the ages of 6 and 15. In about 90% of patients serum ceruloplasmin levels
      and serum copper concentrations are reduced. Copper excreation is increased.
      Histologic examination of liver biopsy specimens reveals fatty infiltration,
      Mallory bodies and ballooned glycogen nuclei, abnormalities which are also found
      in alcoholic liver disease. The definitive diagnostic parameter is the
      quantitative determination of liver copper content (> 250 micrograms/g
      dryweight). Untreated Wilson disease is always fatal. Lifelong treatment with
      anti-copper drugs are essential, D-penicillamine being the firstline therapy.
      Hereditary hemochromatosis (HH) is an iron overload disease inherited as an
      autosomal recessive trait. The frequency of the disease is high. The first
      symptoms usually can be found at the age of 20-50 years. Arthralgia develops in
      up to 50% of the patients. Many organs are involved, most often the liver. The
      organ is usually enlarged, transaminases are always moderately elevated.
      Laboratory findings disclose a marked elevation in serum ferritin and transferrin
      saturation. More than 80% of HH-patients are homozygous for the C282Y-mutation in
      the HFE-gene. The firstline treatment of HH is phlebotomy. Treatment is lifelong.
      When serum ferritin drops below 50 micrograms/l, the frequency of phlebotomy
      should be reduced (4-12 per year). If the patient already has cirrhosis, the risk
      of HCC is very high.

PMID- 12508672
TI  - [Interventions in gastroenterology and hepatology: indications and results].
AB  - Interventional therapy and above all the endoscopic interventions have gained
      importance in the last years. There are a lot of interventional procedures with
      curative or palliative intention, which value have to be compared with surgical
      therapy as the therapeutical gold standard. Today the endoscopic hemostasis for
      ulcer or variceal bleeding are the therapy of choice with very good results. Thus
      the need for surgery is low. The treatment of benign esophageal stenosis is a
      domain of the endoscopic therapy. Dilatation with bougies or balloon dilatation
      get comparable results. In patients with achalasia age and comorbidity of the
      patients are of great importance for the choice of therapy. In young patients the
      botulinum toxin injection should be avoided because of a very low long-term
      efficiency and because surgery become more difficult after botulinum toxin
      injection. As colorectal cancer is a frequent tumor endoscopic polypectomy and
      mucosectomy are very important endoscopic procedures, because there is a
      possibility of cancer prevention and when risk factors are be considered a
      curative therapy of early colorectal cancer is possible.

PMID- 12508673
TI  - [Helicobacter pylori. Update 2002].
AB  - Helicobacter pylori infection has been recognized as the most important
      pathogenetic principal of peptic ulcer disease, atrophic gastritis, gastric
      adenocarcinoma and MALT lymphoma. At the moment efforts are made to clarify it's
      role in functional dyspepsia, and gastro-esophageal reflux disease. The complex
      interactions between H. pylori infection and NSAIDs is another field of ongoing
      research. Diagnosis and eradication therapy are standardized. Established
      indications are peptic ulcer disease, low-grade gastric MALT lymphoma, early
      gastric cancer treated by mucosal resection and partial gastrectomy for gastric
      cancer. Atrophic gastritis, known to be a precancerous lesion, as well as first
      degree relatives of patients with gastric cancer is another widely accepted
      indication for eradication therapy. The recommended eradication regimens combine
      a proton pump inhibitor with clarithromycin and either amoxicillin or
      metronidazole--for a week.

PMID- 12508674
TI  - [Cultural influenza vaccines].
AB  - Recent achievements in development of influenza vaccines using long-term cell
      cultures MDSK or Vero are reviewed. Cell cultures were grown in bioreactors
      (fermenters) filled with microcarriers using serum-free culture media.
      Inactivated cultural influenza vaccines were clinically tested in many countries.
      The results of these trials showed that cultural influenza vaccines are as safe
      and immunogenic as conventional vaccines prepared using chicken embryos. It is
      emphasized that cultural influenza vaccines prepared using serum-free culture
      media have a number of advantages over embryonic influenza vaccines: standard
      preparation technology, intactness of all hemagglutinin antigen domains, absence
      of protein allergens and possible viral contamination inherent in chicken embryos
      and blood serum, and possibility of easy intensification of vaccine production in
      case of influenza pandemic. Taking into consideration these advantages, it may be
      suggested that cultural influenza vaccines will soon be widely used in medical
      practice.

PMID- 12508675
TI  - [Specific antibodies in convalescents after West Nile fever].
AB  - Blood serum samples were obtained from patients with West Nile fever (WNF) from
      the city of Volgograd and its region within the disease weeks 1-3 (July-October
      1999), month 6-7 (May_June 2000) and month 12-18 (May-June 2001) after the
      disease onset. In the sera of 40 patients examined 6-7 months after the disease
      onset IgM-antibodies to WNF virus were absent (dilution 1:50), IgG ones were
      detected in 35 patients (87.5%). 18 months after the disease IgG-antibodies were
      identified in 23 of 26 convalescents (88.5%). The serum samples obtained in
      autumn 1999 and May-June 2000 contained antihemagglutinins to WNF virus for 6-7
      months in all 18 patients. In May-June 2000 the sera were positive in 38
      convalescents who had WNF in 1999.

PMID- 12508676
TI  - [The study of immune structure of Astrakhan region population to West Nile virus
      in 1998 and 1999].
AB  - Immunostructure of the Astrakhan Region population to West Nile fever (WNF) was
      studied in the preepidemic period (1998) and after the outbreak (1999). Among the
      sera obtained in 1998, 63 (26.3%) were positive in neutralization reaction, 84
      (27.1%) in enzyme immunoassay IgG and 20 (7.8%) in HAIR. IgM-antibodies were
      found in none of 142 samples. Overall number of donors having antibodies to WNF
      virus by three reactions reached 97 (31.6%). In the sera obtained in 1999, virus
      neutralizing antibodies were detected in 72(44.4%) cases, specific IgM antibodies
      detected by EIA_in 5(3.1%), IgG_in 44(27.1%), antihemagglutinins_in 11 (6.9%).
      The number of positive findings in 4 reactions in 1999 was 81(50.0%). The results
      of examination of the sera collected for two years (1998 and 1999) were the
      following: of 402 samples examined in NR positive were 135(33.6%), of 304 five
      (1.6%) were IgM positive, 128(27.1%) of 472 were IgG positive, and 31(7.4%) of
      417 responded in HAIR. Overall index of humoral immunity for 2 years was 37.9%
      (in males and females 39.8 and 32.8%, respectively. In persons aged 20-29
      years_36.9%, 50-59 years_42.9%. Thus, by 2-year results, antibodies to WNF virus
      occurred in 51.9% rural citizens and 35.0% city population.

PMID- 12508677
TI  - [Effect of interferon inductors on infection induced by hepatitis C virus and
      activity of mRNA cytokines in cell cultures SW-13 and MT-4].
AB  - An experimental model of hepatitis C virus (HCV) infection in cell culture in
      vitro was used to study the influence of interferon (IFN) inducers on HCV
      infection activity. In combination with the RT-PCR method, this model was also
      used to study the dynamics of cytokine mRNA activity for IFN-alpha, IFN-gamma, IL
      I beta, IL-2, IL-4, IL-6, IL-8, BL-10, IL-12, IL-18, and TNF-alpha. The research
      was carried out using long-term cell cultures SW-13 (human paradrenal
      adenocarcinoma cells) and MT-4 (human cells of lymphoblastoid origin) inoculated
      with HCV under conditions of acute infection. The obtained data showed that cell
      cultures SW-13 and MT-4 were sensitive to replication of HCV (cytopathogenic
      variant). The addition of IFN inducers Savratz, Kagocel, and Cycloferon to
      infected cell cultures usually resulted in suppression of HCV reproduction in
      these cultures. Cycloferon had the greatest antiviral activity (virus titer level
      decreased by a factor of 2.51 g and 5.51 g TCD50 in cell cultures SW-13 and MT-4,
      respectively). It was suggested that induction of IFN-gamma, IL-4 and IL-8 plays
      a certain role in HCV reproduction suppression. The results of this work provide
      an opportunity for more efficacious use of IFN inducers in therapy of HCV
      infection.

PMID- 12508678
TI  - [Test for specific antibodies to virus hepatitis delta based on synthetic
      peptides].
AB  - Solid-phase synthesis of three linear peptides overlapping the major
      immunodominant epitope of HDAg, which located within amino acid (aa) segment 53
      108, and peptide aa 167-179 was carried out. The structure of the peptides
      corresponded to the sequences of isolates HDV type I. Their antigen reactivity
      was studied by indirect enzyme immunoassay with sera from patients with hepatitis
      D and from asymptomatic carriers of anti-delta antibodies. Two B-epitopes located
      within aa 53-80 and 71-93 appeared to be the most immnunoreactive. The use of
      these peptides in ELISA allowed anti-delta IGg antibodies to be detected with 95%
      confidence in serum of patients with hepatitis D and with 87% confidence in serum
      of asymptomatic carriers of anti-delta antibodies. Analysis of obtained data
      showed that these peptides can be used in new diagnostic anti-HDV tests.

PMID- 12508679
TI  - [Analysis of mutations in the genome of cold-adapted strains of influenza A virus
      using extended modification of polymerase chain restriction method].
AB  - Cold-adapted influenza viruses A/Leningrad/13 4/17/5 7 (H2N2) (Len/17) and
      A/Leningrad/I 34/4 7/57 (H2N2) (Len/47) are used in Russia to prepare live
      reassortant cold-adapted influenza vaccines (LIV) for adults and children,
      respectively. Comparison between the nucleotide sequences of the Len/17 strain
      and the initial wild-type strain A/Leningrad/13 4/5 7 (H2N2) revealed ten
      nucleotide substitutions (eight of them encoding). Four additional substitutions
      (three encoding) were found in the genome of the Len/47 virus. Gene segment
      restriction site (PCR-restriction) analysis was used for identification of the
      genotype of reassortant influenza viruses. Conventional methods of PCR
      restriction analysis detect only five encoding nucleotides substitutions in the
      internal genes of the Len/17 and seven substitutions in the internal genes of the
      Len/47 virus. An extended modification of the PCR-restriction method detect all
      encoding mutations in the internal genes of the Len/17 and Len/47 viruses (eight
      and eleven encoding substitutions, respectively). This method is advantageous for
      genome composition analysis of reassortant influenza vaccine strains and for
      investigating the genetic stability of LIV during replication in vaccines.

PMID- 12508680
TI  - [Effectiveness of virazol, realdiron and interferon inductors in experimental
      Omsk hemorrhagic fever].
AB  - Efficacy of drug therapy of Omsk hemorrhagic fever (OHF) was tested
      experimentally using cell culture and laboratory animals infected with the OHF
      virus strain Ondatra. Screening tests showed that high concentrations of Virazol
      or interferon inducers Larifan and Rifastin caused moderately pronounced
      suppression of virus reproduction in cell culture. Realdiron was found to be a
      high-efficacy preparation causing complete inhibition of virus reproduction in
      cell. Larifan demonstrated the highest antiviral efficacy against OHF virus in
      experiments with laboratory animals. This drug prevented the death of 65%
      infected mice and significantly decreased infection process severity in rabbits.

PMID- 12508681
TI  - [Combined use of killed vaccines and immunomodulator ridostin for urgent
      prevention of epidemic stomatitis, Aujeszky disease and carnivore plague in
      experiment].
AB  - Results of experimental studies of mice and pigs infected with foot-and-mouth
      disease virus, minks infected with Aujeszky's disease virus, and dogs infected
      with canine distemper virus are described. In animals with foot-and-mouth disease
      and Aujeszky's disease, combined treatment with killed vaccine and
      immunomodulator Ridostin by the scheme of urgent prophylaxis (3 days before
      infection) caused 75% (foot-and-mouth disease) and 100% (Aujeszky's disease)
      prevention of animal death and development of generalized infection. The use of
      Ridostin by the scheme of urgent prophylaxis in a canine distemper infection
      focus arrested clinical symptoms of the disease in 50% of animals received
      immunomodulator. Clinical symptoms of canine distemper in the other dogs treated
      with immunomodulator were manifested in a mild form, and their appearance was
      delayed to 23-25 days after contact with infected animal.

PMID- 12508682
TI  - [Pilot experience of studying calicivirus infection in Moscow children].
AB  - An RT-PCR-based assay for detecting calicivirus RNA was developed. Samples of
      feces of 124 children patients with acute gastroenteritis were tested for the
      presence of NLV-1, NLV-2, and SLV. Calicivirus infection was detected in 6.4% of
      cases of children with acute gastroenteritis. All isolates were non-homogeneous
      Norwalk like Viruses 2 genotype with maximum nucleotide homology to the strains,
      isolated in UK and Japan. The use of the RT-PCR assay developed in our laboratory
      allowed the etiology of 22.2% of cases of acute gastroenteritis of uncertain
      etiology to be identified.

PMID- 12508683
TI  - [Use of diagnostic DNA probes for detection of the provirus of bovine leukemia
      virus in infected cows].
AB  - A method of detection of BLV proviral DNA in the peripheral blood leukocytes of
      cattle is reported. Leukocytes were used without preliminary cultivation. Cell
      DNA was dot-hybridized with P-labeled plasmid containing a fragment of BLV
      proviral DNA. The sera samples taken from the cattle under study were also tested
      using immunodiffusion assay (ID). The results of comparison showed that dot
      hybridization assay is a more sensitive diagnostic test than ID, because it
      detects BLV infection in apparently normal cattle, which was seronegative in ID.

PMID- 12508684
TI  - [Characteristics of field isolates of Newcastle disease virus isolated in the
      course of outbreaks in the poultry plant in the Leningrad region in 2000].
AB  - A field isolate of Newcastle disease virus (NDV) was isolated in the Russko
      Vysotskaya poultry farm, Leningrad region. Within four days after infection, the
      isolate caused 100% mortality in 60-day-old susceptible chickens. The HA titer of
      the allantoic fluid samples collected after one passage in SPF-chicken embryos
      was 1:512, and it reacted only with the NDV specific antiserum in HI test.
      Intracerebral pathogenicity index and mean embryo death time were 1.97 and 49
      hours, respectively. The isolate has the amino acid sequence of the protease
      cleavage site of the fusion protein F0 (112R-R-Q-R-R-F117), which is similar to
      that in the velogenic strains of NDV. Therefore, it was concluded that the virus
      isolated in this work was an ethiological agent of the ND outbreak in this
      poultry farm.

PMID- 12508685
TI  - [Viral hepatitis].

PMID- 12508687
TI  - Automated breast cancer diagnosis based on fine needle aspiration.
AB  - OBJECTIVE: To design and analyze an automated diagnostic system for breast
      carcinoma based on fine needle aspiration (FNA). STUDY DESIGN: FNA is a
      noninvasive alternative to surgical biopsy for the diagnosis of breast carcinoma.
      Widespread clinical use of FNA is limited by the relatively poor interobserver
      reproducibility of the visual interpretation of FNA images. To overcome the
      reproducibility problem, past research has focused on the development of
      automated diagnosis systems that yield accurate, reproducible results. While
      automated diagnosis is, by definition, reproducible, it has yet to achieve
      diagnostic accuracy comparable to that of surgical biopsy. In this article we
      describe a sophisticated new diagnostic system in which the mean sensitivity (of
      FNA diagnosis) approaches that of surgical biopsy. The diagnostic system that we
      devised analyzes the digital FNA data extracted from FNA images. To achieve high
      sensitivity, the system needs to solve large, equality-constrained, integer
      nonlinear optimization problems repeatedly. Powerful techniques from the theory
      of Lie groups and a novel optimization technique are built into the system to
      solve the underlying optimization problems effectively. The system is trained
      using digital data from FNA samples with confirmed diagnosis. To analyze the
      diagnostic accuracy of the system > 8,000 computational experiments were
      performed using digital FNA data from the Wisconsin Breast Cancer Database.
      RESULTS: The system has a mean sensitivity of 99.62% and mean specificity of
      93.31%. Statistical analysis shows that at the 95% confidence level, the system
      can be trusted to correctly diagnose new malignant FNA samples with an accuracy
      of 99.44-99.8% and new benign FNA samples with an accuracy of 92.43-93.93%.
      CONCLUSION: The diagnostic system is robust and has higher sensitivity than do
      all the other systems reported in the literature. The specificity of the system
      needs to be improved.

PMID- 12508688
TI  - Discriminant analysis of image karyometric variables in benign and malignant
      melanocytic skin lesions.
AB  - OBJECTIVE: To perform a quantitative analysis to identify which of 7 nuclear
      morphometry-related variables are of diagnostic value in distinguishing benign
      from malignant melanocytic skin lesions. STUDY DESIGN: At the Institute of
      Pathology, University of Nis, formalin-fixed, paraffin-embedded skin biopsies
      from 23 cases of benign nevi (18 intradermal and 5 junctional) and 25 cases of
      primary nodular malignant melanomas were retrieved. Specimens were routinely
      stained with hematoxylin and eosin and analyzed using a computer-assisted
      interactive image analysis system. Nuclear area, equivalent diameter, volume of
      equivalent sphere, perimeter, mean chord, circularity and integrated optical
      density were estimated after manual editing of binary images. RESULTS: In
      univariate analysis, 6 features were found to be significantly different between
      the benign and malignant groups (P < .0001); all measured nuclear variables
      (except circularity) were higher in malignant melanomas. No significant
      differences were found among lesions with respect to nuclear shape. Using
      discriminant function analysis, a correct diagnosis was achieved in 95.8% of
      benign nevi cases and 84.0% of malignant melanoma cases. The best discriminant
      variable was nuclear area. CONCLUSION: Image analysis is diagnostically relevant
      to the evaluation of melanocytic lesions of the skin. The area of the nucleus
      appeared to have potential for differentiating benign from malignant tumors and
      can be estimated in the course of routine histology.

PMID- 12508689
TI  - Neural network-based segmentation and classification system for automated grading
      of histologic sections of bladder carcinoma.
AB  - OBJECTIVE: To develop an image analysis system for automated nuclear segmentation
      and classification of histologic bladder sections employing quantitative nuclear
      features. STUDY DESIGN: Ninety-two cases were classified into three classes by
      experienced pathologists according to the WHO grading system: 18 cases as grade
      1, 45 as grade 2, and 29 as grade 3. Nuclear segmentation was performed by means
      of an artificial neural network (ANN)-based pixel classification algorithm, and
      each case was represented by 36 nuclei features. Automated grading of bladder
      tumor histologic sections was performed by an ANN classifier implemented in a two
      stage hierarchic tree. RESULTS: On average, 95% of the nuclei were correctly
      detected. At the first stage of the hierarchic tree, classifier performance in
      discriminating between cases of grade 1 and 2 and cases of grade 3 was 89%. At
      the second stage, 79% of grade 1 cases were correctly distinguished from grade 2
      cases. CONCLUSION: The proposed image analysis system provides the means to
      reduce subjectivity in grading bladder tumors and may contribute to more accurate
      diagnosis and prognosis since it relies on nuclear features, the value of which
      has been confirmed.

PMID- 12508690
TI  - DNA cytometry in pleomorphic adenomas with cytologic atypia.
AB  - OBJECTIVE: To investigate the nuclear DNA content of pleomorphic adenomas with
      cytologic atypia. STUDY DESIGN: Analysis was performed on new, fuchsin-stained
      samples of 10 selected cases of pleomorphic adenoma with cytologic atypia.
      Morphometric analysis was done by a computer-assisted image cytometry system and
      consisted of the determination of DNA indices, Auer DNA histogram types, and 3c
      and 5c exceeding rates. RESULTS: Eight cases were diploid and two cases aneuploid
      according to the DNA index. The Auer histogram was type I in five cases and type
      III in the others. In the two aneuploid cases the 3c exceeding rate was > 10% and
      the 5c exceeding rate > 1%. CONCLUSION: Atypical cells in pleomorphic adenomas
      with cytologic atypia carry abnormal amounts of DNA. Image cytometry can make
      detecting very low numbers of aneuploid cells easier due to its higher resolution
      as compared to that of flow cytometry.

PMID- 12508691
TI  - Cardiomyocyte volume-weighted nuclear volume and spironolactone therapy in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To evaluate the blood pressure (BP) and cardiomyocyte nuclei
      hypertrophy of spontaneously hypertensive rats (SHR) treated with spironolactone
      and with spironolactone and an angiotensin-converting enzyme inhibitor and
      calcium channel blocker. STUDY DESIGN: Six groups with 5 SHR each were treated
      for 13 weeks: control group, spironolactone groups (5, 10 and 30 mg/kg/d, or low,
      moderate and high doses, respectively), and spironolactone and enlapril or/and
      verapamil. Blood pressure (BP) and cardiomyocyte volume-weighted nuclear volume
      (VWNV) were studied. RESULTS: The usual evolution of BP in young adult SHR was
      greatly altered by spironolactone treatment, with either attenuation or reversion
      of the BP tendency to increase. The treatments efficiently reduced the
      cardiomyocyte VWNV > 45%, confirming efficient action of both spironolactone
      monotherapy at moderate and high dose and spironolactone combined with enalapril
      or verapamil. However, the high dose of spironolactone, and spironolactone plus
      enalapril or verapamil showed no significant differences in cardiomyocyte VWNV.
      Correlation between VWNV and BP (13th week) suggested that BP degree influences
      cardiomyocyte VWNV. CONCLUSION: The effect of spironolactone monotherapy seems to
      be dose dependent, and the combination with enalapril or verapamil improves
      spironolactone efficiency in BP reduction but not in prevention/attenuation of
      cardiac myocyte nuclear hypertrophy.

PMID- 12508693
TI  - Normal value for the direct micronucleus test on peripheral blood mononuclear
      cells from healthy donors.
AB  - OBJECTIVE: To obtain the normal value of micronuclei in peripheral blood
      mononuclear cells. STUDY DESIGN: We screened 300 blood samples for micronucleated
      cells. Samples from donors who smoked, were ill or lived in a polluted area were
      excluded. From each sample, 500 swollen mononuclear leukocytes were screened with
      a light microscope, using 400x magnification. A frequency distribution of
      micronucleated cell number was made, and the mean of micronucleated cell number
      was calculated. Further, the data were tested for the type of probability
      distribution using the test of goodness of fit, and the parameters were
      estimated. RESULTS: Of the 300 samples, 203 were excluded and 97 analyzed. In the
      97 samples, the mean of micronucleated cells (from 500 cells screened) was 0.59;
      the data followed a Poisson distribution. The 95% confidence limits were .45 and
      .76. CONCLUSION: The normal value in unexposed individuals is .59 micronucleated
      cells per 500 cells.

PMID- 12508692
TI  - Bronchoalveolar lavage fluid differential cell count. How many cells should be
      counted?
AB  - OBJECTIVE: To investigate the number of cells to be counted in cytocentrifuged
      bronchoalveolar lavage (BAL) fluid preparations in order to reach a reliable
      enumeration of each cell type. STUDY DESIGN: A total of 136 BAL fluid samples for
      patients with suspected pneumonia or interstitial lung disease were investigated.
      Differential cell counts were performed on May-Grunwald-Giemsa-stained
      cytocentrifuged preparations by 2 observers, each differentiating 500 cells.
      Reliability for the enumeration of each cell type was expressed as phi value, as
      calculated in generalizability theory. RESULTS: For polymorphonuclear neutrophils
      (PMNs), alveolar macrophages, lymphocytes and eosinophils, an acceptable phi
      value of > or = .95 was reached at a count of 300 cells by 1 observer. Mast cells
      reached a phi value of only .674 at a count of 500 cells by 1 observer,
      precluding a reliable count. At a count of 500 cells by 1 observer, squamous
      epithelial cells, bronchial epithelial cells and plasma cells displayed phi
      values of .868, .903 and .816, respectively. CONCLUSION: At a count of 300 cells,
      PMNs, alveolar macrophages, lymphocytes and eosinophils are reliably enumerated
      in cytocentrifuged BAL fluid samples.

PMID- 12508694
TI  - Independent prognostic value of hormone receptor expression and S-phase fraction
      in advanced breast cancer.
AB  - OBJECTIVE: TO assess the prognostic value of immunocytochemically assessed
      hormone receptor expression and DNA flow cytometry data in advanced breast
      cancer. STUDY DESIGN: This prospective study with long-term follow-up evaluated
      the above parameters in relation to overall survival in 392 patients with
      advanced breast cancer (stages IIB, n = 106; IIIA, n = 66; IIIB, n = 174; and IV,
      n = 46) using fine needle aspiration cytology. RESULTS: Estrogen and progesterone
      receptor positivity was detected in 65.1% and 46.1% of the tumors, respectively.
      DNA aneuploidy was present in 70.9% of the cases, and the median S-phase fraction
      (SPF) was 9.4%. There was a significant correlation of aneuploidy and high SPF
      with lack of hormone receptors. The median SPF and SPF tertiles (cutoff values,
      6.5% and 12%), applied in the whole series, showed a significant correlation with
      survival, whereas if SPF was used according to ploidy status, no prognostic
      significance was found. No differences in relation to survival among different
      DNA aneuploidy subclasses were verified. In univariate analysis, clinical
      staging, hormone receptors, DNA ploidy and SPF showed a statistically significant
      correlation with the overall survival. In multivariate analysis only DNA ploidy
      did not maintain independent prognostic significance. CONCLUSION: Hormone
      receptor expression and flow cytometric SPF are independent prognostic factors in
      advanced breast cancer.

PMID- 12508695
TI  - Flow cytometry and factor analysis evaluation of confocal image sequences of
      morphologic and functional changes occurring at the mitochondrial level during 7
      ketocholesterol-induced cell death.
AB  - OBJECTIVE: To analyze functional and morphologic alterations that occur at the
      mitochondrial level by flow cytometry and laser scanning confocal microscopy
      (CLSM) combined with factor analysis of biomedical image sequences (FAMIS). STUDY
      DESIGN: Under treatment of U937 cells with 7-ketocholesterol, functional
      alterations that occur at the mitochondrial level (especially loss of
      transmembrane mitochondrial potential [delta psi m]) were assessed with 3,3'
      dihexyloxacarbocyanine iodide (DiOC6(3)) and mitotracker red (CMXRos), whereas
      morphologic changes were analyzed with nonyl acridine orange (NAO). By flow
      cytometry, these different dyes were excited at 488 nm, whereas on CLSM,
      excitation of NAO and CMXRos was performed by lines of an argon laser. By CLSM,
      spectral sequences were performed to characterize NAO and CMXRos. FAMIS was used
      to transform the image sequences in factor images. RESULTS: By flow cytometry,
      rapid loss of delta psi m induced by 7-ketocholesterol was detected with both
      DiOC6(3) and CMXRos, which gave similar results. Morphologic alterations of
      mitochondria were revealed with NAO. The factor images obtained from confocal
      image sequences confirmed these results. CONCLUSION: The simultaneous use of NAO,
      CMXRos and FAMIS constitutes a new method to detect morphologic and functional
      alterations occurring at the mitochondrial level during cell death.

PMID- 12508696
TI  - Psychopathy, treatment involvement, and subsequent violence among civil
      psychiatric patients.
AB  - Individuals with psychopathy typically are viewed as incurable cases that should
      be diverted from treatment settings to environments where their behavior can be
      monitored and controlled. The prevailing clinical conviction that psychopaths are
      untreatable has crucial implications, given the scarcity of mental health care
      resources, the number of legal contexts that call for assessment of treatability,
      and the explosion of research on psychopathy and violence risk over recent years.
      Based on a sample of 871 civil psychiatric patients (including 195 "potentially
      psychopathic" and 72 "psychopathic" patients), this study explores the relations
      among psychopathy, receipt of outpatient mental health services in real-world
      settings, and subsequent violence in the community. The results suggest that
      psychopathic traits do not moderate the effect of treatment involvement on
      violence, even after controlling statistically for the treatment assignment
      process. Psychopathic patients appear as likely as non-psychopathic patients to
      benefit from adequate doses of treatment, in terms of violence reduction. We
      interpret these results in light of prior research with offenders and analyze
      their implications for future research, policy, and practice.

PMID- 12508697
TI  - An analysis of the effects of subjective and objective instruction forms on mock
      juries' murder/manslaughter distinctions.
AB  - Defendants' emotions at the time of their crimes may potentially serve as
      mitigating circumstances in murder/manslaughter cases. The present study examined
      whether differences between two forms of instructions given juries in such cases
      affected mockjuries' murder/manslaughter distinctions. Jurors' reasons for their
      verdicts and definitions of murder and manslaughter were also compared. In
      addition, three factors found to be predictive of murder/manslaughter
      distinctions in previous research were evaluated. It was found that, though
      instruction forms affected jurors' stated reasons for their verdicts and their
      definitions of murder and manslaughter, they did not significantly affect
      murder/manslaughter distinctions. Defendants were most likely to be convicted of
      murder if they had a history of violence with the victim and dwelt upon their
      emotions. We suggest jurors likely construe instructions given them to fit their
      a priori understandings of murder, manslaughter, and the potentially mitigating
      role of defendants' emotions.

PMID- 12508698
TI  - Do juries meet our expectations?
AB  - Surveys of public opinion indicate that people have high expectations for juries.
      When it comes to serious crimes, most people want errors of convicting the
      innocent (false positives) or acquitting the guilty (false negatives) to fall
      well below 10%. Using expected utility theory, Bayes' Theorem, signal detection
      theory, and empirical evidence from detection studies of medical decision making,
      eyewitness testimony, and weather forecasting, we argue that the frequency of
      mistakes probably far exceeds these "tolerable" levels. We are not arguing
      against the use of juries. Rather, we point out that a closer look at jury
      decisions reveals a serious gap between what we expect from juries and what
      probably occurs. When deciding issues of guilt and/or punishing convicted
      criminals, we as a society should recognize and acknowledge the abundance of
      error.

PMID- 12508699
TI  - Age differences in lineup identification accuracy: people are better with their
      own age.
AB  - Previous research has reported that young adults are better at eyewitness face
      recognition than are older adults. However, these studies have used young adults
      as culprits and fillers. We explore how the relative ages of the witness and the
      culprit influence eyewitness accuracy in 2 experiments. In the first experiment,
      young (18-25 years old) and older (35-55 years old) adults each saw 4 crime
      videos. In 2 the culprit was a young adult and in 2 the culprit was an older
      adult. Participants were more accurate at identifying the culprit when viewing
      culprit present lineups comprising people of their own age: an "own age bias"
      analogous to the own race bias. In the 2nd experiment, using a similar procedure,
      young (18-33 years old) and older (40-55 years old) adults viewed both culprit
      present and culprit absent lineups. The results of the first experiment were
      replicated for the culprit present lineups. However, no own age bias was found
      for the culprit absent lineups. Implications for police procedures dealing with
      cross-generation identifications are discussed.

PMID- 12508700
TI  - Expert testimony pertaining to battered woman syndrome: its impact on jurors'
      decisions.
AB  - Participants (N = 200) were presented with a criminal homicide trial involving a
      battered woman who had killed her abuser. Within the trial, both the response
      history (passive, active) and presence of expert testimony pertaining to battered
      woman syndrome (present, absent) were systematically varied. As well, half of the
      participants in each of these conditions were provided with a nullification
      instruction informing them that they were free to disregard the law and acquit
      should a strict application of the law result in an unjust verdict. Results
      indicated that, compared to the passive response condition, the mock jurors were
      no less receptive to the expert testimony in the active response condition. The
      impact of the testimony on participants' verdicts, however, was moderated by the
      nullification instruction. That is, although the presence of the testimony did
      result in greater verdict leniency, this only occurred when the mock jurors had
      been released from a strict application of the law. The implications of these
      findings are discussed.

PMID- 12508701
TI  - The effects of SCHIP on children's health insurance coverage: early evidence from
      the community tracking study.
AB  - The State Children's Health Insurance Program (SCHIP) was designed to increase
      the number of children with health insurance coverage without resulting in large
      numbers of children substituting public coverage for private insurance. This
      study uses data from the Community Tracking Study collected before and after
      SCHIP implementation to examine the effects of increases in eligibility for
      public coverage on children's health insurance coverage. Using a regression-based
      difference-in-differences approach, the authors find that increases in
      eligibility for public coverage did increase the likelihood of having Medicaid or
      other state coverage versus being uninsured for the primary SCHIP target
      population--children in families with incomes between 100 and 200 percent of the
      federal poverty level. However, eligibility increases also increased the
      likelihood of having public coverage versus private insurance for this income
      group, indicating that SCHIP expansions resulted in substitution of public for
      private insurance. In fact, simulation results indicate that the initial impact
      of SCHIP on private insurance coverage has been far greater than on uninsurance
      rates. These results reflect the early stages of SCHIP implementation, however,
      and are subject to change as the SCHIP programs mature.

PMID- 12508702
TI  - Access to medical care for low-income persons: how do communities make a
      difference?
AB  - This paper considers the impact of community-level variables over and above the
      effects of individual characteristics on healthcare access of low-income children
      and adults residing in large metropolitan statistical areas (MSAs). Further, we
      rank MSAs' performance in promoting healthcare access for their low-income
      populations. The individual-level data come from the 1995 and 1996 National
      Health Interview Survey (NHIS). The community-level variables are derived from
      multiple public-use data sources. The outcome variable is whether low-income
      individuals received a physician visit in the past twelve months. The proportion
      receiving a visit by MSA varied from 63% to 99% for children and from 62% to 83%
      for adults. Access was better for individuals with health insurance and a regular
      source of care and for those living in communities with more federally-funded
      health centers. Children residing in MSA.

PMID- 12508703
TI  - Structure, process, and satisfaction with obstetricians: an analysis of mainland
      Puerto Ricans.
AB  - This study examines various dimensions of satisfaction with obstetricians among
      mainland Puerto Ricans using data from a survey administered to a representative
      sample of 1,219 Puerto Rican mothers. The results indicate that the majority of
      Puerto Rican women are satisfied with their obstetricians, but they are not
      typically "extremely" satisfied. Moreover, satisfaction is influenced by the
      structure of care, the process of care, and the outcome of care. Two aspects of
      process that are especially important are the continuity and content of care.
      Although satisfaction is not generally associated with the ethnicity or the
      gender of physicians, some evidence suggests that patients who utilize public
      facilities or lack continuity of care tend to be more satisfied if they have a
      female physician.

PMID- 12508704
TI  - Employer-sponsored insurance: how much financial protection does it provide?
AB  - The authors examine the generosity of private employer health insurance coverage
      using data from two large national surveys of employers. Generosity is measured
      as the expected out-of-pocket share of medical expenditures for a standard
      population, given the provisions of the coverage. On average, those covered by
      employer-sponsored insurance can expect to pay 25 percent of expenditures out of
      pocket. There is little variability across plans in this share, though plans
      offered by smaller employers are somewhat less generous than those offered by
      larger employers. Individuals who incur high costs pay a smaller share of the
      bill than do those with lower levels of spending. The generosity of employer
      sponsored plans increased slightly in the 1990s.

PMID- 12508705
TI  - From physician to consumer: the effectiveness of strategies to manage health care
      utilization.
AB  - Many strategies are commonly used to influence physician behavior in managed care
      organizations. This review examines the effectiveness of three mechanisms to
      influence physician behavior: financial incentives directed at providers or
      patients, policies/procedures for managing care, and the selection/education of
      both providers and patients. The authors reach three conclusions. First, all
      health care systems use financial incentives, but these mechanisms are shifting
      away from financial incentives directed at the physician to those directed at the
      consumer. Second, heavily procedural strategies such as utilization review and
      gatekeeping show some evidence of effectiveness but are highly unpopular due to
      their restrictions on physician and patient choice. Third, a future system built
      on consumer choice is contradicted by mechanisms that rely solely on narrow
      networks of providers or the education of physicians. If patients become the new
      locus of decision making in health care, provider-focused mechanisms to influence
      physician behavior will not disappear but are likely to decline in importance.

PMID- 12508706
TI  - Considerations on 100 cases of free microsurgical flaps in the reconstruction of
      the soft tissues of the lower limb.
AB  - The authors evaluate the results for 100 cases of severe loss of substance of the
      lower limb treated by microvascular free flaps at the Division of Plastic
      Surgery, Bellaria Hospital in Bologna, between 1994 and 2001. The cases involved
      recent traumatic loss of substance in 48 cases, post-traumatic defects such as
      osteomyelitis, ulcers, unstable scarring, sequelae of burns in 40, and neoplasms
      in 12. Muscular flaps were used in 89 cases, skin flaps in 9, a flap of the
      omentum in 1; the latissumus dorsi flap was that most frequently used (50 cases).
      A total of 87 cases had favorable results, while in 13 cases there was failure of
      the flap. Based on the results obtained, and experience, current indications and
      causes of failure are discussed.

PMID- 12508707
TI  - Tendinous cutaneous dorsal hand injuries. One-stage reconstruction.
AB  - The reconstruction of complex cutaneous tendinous dorsal hand injuries represents
      a problem that is not easy to solve. The transferral in a single surgical stage,
      with a single flap, of skin, tendons, and nerves, all completely vascularized, is
      probably the ideal solution. Between 1988 and 1999 the one-stage reconstruction
      method was used in 13 patients. A cutaneous tendinous dorsalis pedis free flap
      was used in 7 cases, and a cutaneous tendinous radial forearm island flap with an
      inverted flow was used in 6. The dorsalis pedis flap allows for the inclusion of
      4 tendons that are completely vascularized (extensor digitorum communis), while
      the radial flap allows us to completely insert a single tendon (palmaris brevis)
      and two vascularized tendinous strips taken from the flexor carpi radialis and
      from the brachioradialis. All of the flaps transferred survived perfectly with
      good functional recovery. One-stage reconstruction that is "completely
      vascularized" allows us to reduce the amount of time spent in hospital, the
      number of operations, and above all it provides cosmetic and functional results
      that are close to normal. The dorsalis pedis flap is indicated in cases of
      cutaneous tendinous dorsal hand injuries that require the simultaneous
      reconstruction of three or four extensor tendons. On the other hand, the radial
      flap may be used in situations where it is necessary to reconstruct only 1 or 2
      tendons.

PMID- 12508708
TI  - Spondylectomy (thoracolumbar spine) combined with dural resection for bone tumor:
      surgical technique.
AB  - The authors describe the technique of vertebral resection combined with resection
      and reconstruction of the dura mater for bone tumor. The literature relevant to
      this topic is reviewed.

PMID- 12508709
TI  - Locked nailing in subtrochanteric fractures of the femur in the elderly patient.
AB  - Subtrochanteric fractures are a typical pathology in the elderly patient, they
      are not very common and they are difficult to treat. The general conditions of
      these patients, often at the limit of operability, are further compromised by
      surgery and time spent in bed, leading to the death of the patient in a high
      percentage of cases. The fracture is often spyroid, it has multiple fragments,
      with interruption of the medial cortical bone. The quality of the bone, because
      of the marked osteoporosis, does not guarantee the good hold of the means of
      fixation used. The use of intramedullary nailing is a safe method, that allows
      for stabilization of the fracture without excessive blood loss, it allows for
      early partial weight-bearing and it has a lower number of complications as
      compared to other methods. Between 1-1-97 and 31-12-00 a total of 59
      persubtrochanteric fractures were treated; there were 15 males and 44 females. A
      Gamma Long nail was used in 46 cases, a Gamma Standard in 13. Eleven of the
      patients died within 6 months. A total of 27 patients aged an average of 78 years
      (minimum 65, maximum 87) were evaluated at a mean follow-up of 10 months (minimum
      7, maximum 27). A Gamma Long nail had been used in 18 cases, and Gamma Standard
      in 8. Partial weight-bearing was allowed after a mean of 20 days (minimum 10,
      maximum 35), total weight-bearing after a mean of 60 days (minimum 40, maximum
      75). Consolidation was obtained after a mean of 4 months (minimum 3, maximum 7).
      There were no significant complications.

PMID- 12508710
TI  - The results of the surgical treatment of 64 patients with thoracic and lumbar
      fracture.
AB  - A total of 64 patients surgically treated for vertebral fractures were evaluated
      clinically and radiographically after a mean time of 49.55 months (from 1 to
      124). There were 50 males and 14 females. Mean age at the time of surgery was
      40.67 years (from 17 to 71). Fractures were divided based on the Denis
      classification system: comminuted fractures: 45; fractures caused by flexion
      distraction: 2; fracture-dislocation: 17; 31 of the fractures were localized at
      the lumbar level, 30 in the dorsal region, 3 at the dorsolumbar passage.
      Neurologic evaluation was carried out on admission and at follow-up using the
      Frankel classification system: type A: 22; type B: 13; type C: 7; type D: 6; type
      E: 16. 56.25% of the patients (36 cases) were classified as having multiple
      trauma. Of the 64 patients, 38 had reduction and stabilization within 6 hours of
      trauma, 26 were treated after a mean time of 2.7 days (from 1 to 6). Harrington
      Luque stabilization was carried out in 5 patients, using the Hartshill rectangle
      in 59. The mean time for hospitalization was 27.68 days (from 9 to 91). Follow-up
      showed neurologic recovery in all of the patients operated on, with the exclusion
      of those classified as Frankel A, without sacral sparing. Despite the residual
      kyphosis and the final anatomic findings which were not always satisfactory, the
      methods used allowed us to obtain results that could be compared to those
      obtained by other means of fixation and more complex techniques.

PMID- 12508711
TI  - Conjoined fracture-dislocation of the forearm at the elbow.
AB  - Conjoined fracture-dislocation of the elbow were first described by Marotte in
      1982. In this study, a total of 41 patients treated between 1975 and 1995 at the
      Rizzoli Orthopaedic Institute and 4 patients treated between 1997 and 2000 at the
      Division of Orthopaedics at the Maggiore Hospital are evaluated. Based on the
      Marotte classification, the patients are divided into 4 groups, by site of
      dislocation of the radial capitellum and amount of comminution of the fracture of
      the ulna. A clinical and radiographic evaluation was made after a mean follow-up
      of 5.3 years based on Anderson criteria. The results obtained were excellent in
      17 patients (37.8%) satisfactory in 13 (28.9%), dissatisfactory in 12 (26.7%); 3
      patients were considered to be failures (6.7%), the best results were obtained in
      type I anterior dislocations.

PMID- 12508712
TI  - Disseminated intravascular coagulation during total hip replacement.
AB  - Disseminated intravascular coagulation (DIC) is an extremely serious hemorrhagic
      disorder and one that is potentially lethal. DIC is more frequently observed as a
      complication of obstetric pathologies, diffused neoplasms, bacterial sepsis,
      blood transfusions, traumas and adipose embolias. The literature reports very few
      cases occurring after total hip replacement, two of which the cause of death. In
      all of the cases described one or boh prosthetic components are cemented. The
      authors report a case observed after total hip replacement in a patient submitted
      one year previously to contralateral hip replacement. Severe hypotension,
      bradychardia and profuse bleeding of the wound and from the drainages one hour
      after suturing constituted the initial symptom. Recognition of the clinical
      findings, after exclusion of a iatrogenic lesion, and subsequent treatment in
      intensive therapy allowed us to save the patient. The syndrome must be suspected
      and immediately diagnosed when profuse bleeding that cannot be related to
      vascular lesion is observed immediately postsurgery after cemented or hybrid hip
      replacement. Confirmation through hematological tests and timely treatment in a
      specialized center are indispensable requirements to save the life of the
      patient.

PMID- 12508713
TI  - Schwannoma of L3.
AB  - The authors report a case of large retroperitoneal schwannoma with osteolysis of
      the pedicle of L3, submitted to complete excision by partial vertebrectomy of L3
      with a combined approach. Schwannoma is a hamartoma constituted by Schwann's
      cells, that causes non-specific clinical manifestations. Image diagnosis provides
      information as to the relationships that the neoformation contracts with the
      surrounding structures, but a definitive diagnosis is exclusively
      anatomopathologic. Retroperitoneal localization is rather rare (0.5-5% of cases).
      Treatment is represented by surgical excision. Because it is a benign, slow
      growing neoplasm, when dealing with cases that are difficult to treat surgically
      or when complete excision means disabling neurovascular lesions, we may opt for
      the incomplete removal of the mass, as long as the case is carefully monitored
      over time.

PMID- 12508714
TI  - [Trigeminal neuralgia and hemifacial spasm. Vessel-nerve antagonism].
AB  - In the last 30 years, the concept of microvascular compression has achieved
      widespread acceptance. Still, some remain unconvinced. A review of our 182
      operations, 104 trigeminal neuralgia and 78 hemifacial spasms, shows that
      microvascular decompression of the trigeminal and facial nerves is effective in
      alleviating trigeminal neuralgia and hemifacial spasm, because it removes the
      actual cause of the disorder rather than simply causing local injury to the
      nerve. Our neurophysiological investigations, the so-called abnormal muscle
      response, performed intraoperatively in twenty patients with hemifacial spasm,
      confirm that compression of the facial nerve at the root exit zone, by a blood
      vessel, causes pathological and clinical responses. Microvascular decompression
      is an extremely safe and effective treatment, even for the older patients without
      severe disabilities.

PMID- 12508715
TI  - Alterations of non-enzymatic biochemistry in uremia, diabetes, and
      atherosclerosis ("carbonyl stress").
AB  - Aging is accompanied by a progressive and irreversible non-enzymatic modification
      of protein by carbohydrates, eventually yielding the advanced glycation end
      products (AGEs). Age generation (Maillard reaction) is markedly augmented in
      diabetes with sustained hyperglycemia but also in normoglycemic uremia and
      atherosclerosis. Recent studies have brought new insights into broad derangements
      in non-enzymatic biochemistry involving not only carbohydrates but also lipids,
      present in diabetes, uremia, and atherosclerosis. The latter have in common
      increased levels of reactive carbonyl compounds (RCOs) with attendant protein
      modifications ("carbonyl stress"). Carbonyl stress might be derived from 1)
      hyperglycemia (lipemia), 2) oxidative stress, and/or 3) impaired detoxification
      of RCOs. Manipulation of carbonyl stress in diabetes, uremia and atherosclerosis
      opens new therapeutic approaches including redox modulation, RCO detoxification,
      and carbonyl stress inhibition. The first generation of carbonyl stress
      inhibitors such as aminoguanidine trap RCOs with its hydrazine group.
      Unfortunately, aminoguanidine (AG) traps pyridoxal as well as noxious RCOs, so
      that its long-term administration in animals results in vitamin B6 deficiency and
      neurotoxicity. Fortunately, newer compounds devoid of such side effects, have
      opened exciting prospects. Widely used hypotensive agents, such as angiotensin
      converting enzyme (ACE) inhibitor and angiotensin II receptor antagonist, but not
      calcium blockers, prove more effective than AG in attenuating the production of
      AGEs. Unlike AG, they do not act as RCO trapping agents, but impact upon the
      production of RCO precursors by scavenging a variety of radicals and altering
      oxidative stress, a mechanism similar to that involved in the inhibitory action
      of nitric oxide on AGE formation. These results provide a new framework to assess
      families of compounds according to their mechanisms of action.

PMID- 12508716
TI  - [Recent findings on the role of cytokines in the pathogenesis of interstitial
      pulmonary fibrosis].
AB  - Cytokines are important mediators of the pathogenesis of lung fibrosis. The
      experimental studies carried out in our laboratory have used a murine model of
      lung silicosis to explore the activity of interleukin-9, -10 and -12. The data
      presented in this short overview illustrate the pro-fibrotic activity of anti
      inflammatory cytokines (IL-10), and the role of type 2 immune polarisation, as
      illustrated by the paradoxical effect of IL-9 and the activity of IL-12 p40
      subunit.

PMID- 12508717
TI  - [Evaluation of dreams by the neuropsychological approach. Utility in the
      characterization of cerebral correlates in oneiric activity by functional
      neuroimaging].
AB  - Recent neuroimaging studies show that human REM sleep is characterized by a
      specific pattern of regional brain activity. While being usually interpreted in
      relation to physiological and cellular mechanisms, the regionally-specific
      distribution of brain activity during REM sleep may also be linked to specific
      dream features. Remarkably, several bizarre features of dreams present
      similarities with wellknown neuropsychological syndromes after brain damage, such
      as delusional misidentifications for faces and places. We propose that
      neuropsychological analysis of dream content might offer new ways of interpreting
      neuroimaging maps, as well as specific predictions for future neuroimaging
      studies.

PMID- 12508718
TI  - [Coronal leakage reconsidered].
AB  - The aim of the present study was to evaluate the impact of the quality of the
      coronal restoration and of the root filling on periapical health. In a sample of
      937 root filled teeth which had not received restorative treatment in the
      previous year, the technical quality of the coronal restorations and of the root
      fillings was radiographically scored; in addition the technical quality of the
      coronal restorations was clinically scored as well. The data showed that the
      technical standard of both coronal restoration and root filling were essential to
      periapical health. The study also showed the relatively limited value of
      epidemiologic findings. Epidemiologic research is descriptive as well as
      analytical in approach. According to the present data, endodontic failure cannot
      be fully explained by radiographic analysis only. Nevertheless, epidemiologic
      data remain a valuable component to the source of knowledge regarding etiologic
      factors and proper treatment procedures in order to improve the results of
      endodontic practice.

PMID- 12508719
TI  - [Status of dental caries in Belgium and neighboring countries].
AB  - The present review describes the evolution of dental health in the Belgian
      population in the last 30 years, comparing it to other European countries. The
      studies carried out in the individual regions of Wallonia, Brussels and Flanders
      and in some municipalities, give a general idea about dental health in the
      country. In the last decade, dental health in Belgian children and adolescents
      has improved markedly. However, a specific health policy is required for risk
      groups such as socio-economically underprivileged, disabled and immigrant
      children. Belgium may be placed among other European countries which show low
      caries prevalence in schoolchildren population. Further investigation in young
      adults and adults are required. The lack of representative data for the whole
      country suggests that the implementation of a data base system for monitoring the
      evolution of dental health in Belgium would be useful.

PMID- 12508720
TI  - [Periodontal health and care needs in a sample of the Belgian population].
AB  - An epidemiological survey was carried out of among staff members of the Catholic
      University of Louvain. A total of 402 subjects, age 35 to 65, were examined.
      Periodontal lesions were estimated using the CPITN index (WHO). Only one subject
      presented no signs of gingival bleeding in any part of the mouth. 41.4% of the
      subjects presented a deep periodontal pocket in at least one sextant. Many
      subjects, although not presenting deep or moderately deep periodontal pockets
      (28.5%) needed scaling and rootplanning or other treatments to eliminate plaque
      retentive factors. In this sample, representing a socio-economically favoured
      segment of the population, we revealed a significant prevalence of periodontal
      disease from mild chronic gingivitis to deep pockets. Requirements in terms of
      care are considerable, ranging from oral hygiene instruction to control plaque to
      specialised care.

PMID- 12508721
TI  - [Review of currently used periodontal indexes].
AB  - Several commonly used indices to assess periodontal and dental health are
      reviewed. A comparison is made between the different methods of scoring the
      signs, symptoms and etiologic factors of periodontal diseases.

PMID- 12508722
TI  - [Varicocele and cryptorchism: diagnosis and follow up].
AB  - The state of art of ultrasound technology has reached a fundamental role, due to
      the color Doppler methodology, in the study and diagnosis of scrotal pathologies,
      especially those related to vascular, neopalstic and inflammatory disease. The
      varicocele is one of the most frequent causes of male infertility, even in the
      sub-clinical forms. The role of echo-Doppler is to achieve a diagnostic
      conclusion in the sub-clinical forms, to suggest the type and value of clinical
      varicocele, to give morphological and structural informations of the scrotal
      contents, useful for the therapeutic choice and follow-up, to evaluate the
      therapy success, the eventual persistency or recurrence. Moreover, in the
      undescended testis the ultrasound technique represents the best non-invasive
      diagnostic means. This technique allows to disclose the undescended testis, up to
      the supra-lateral angle of bladder, to evaluate it in both the volumetric and
      echostructural aspect and to correlate those data to that of contra-lateral
      normosited testis and to the per age standards. On the other hand, echography
      results in less utility in the abdominal undescended testis.

PMID- 12508723
TI  - [Echo-color-Doppler in male pelvic congestion syndrome].
AB  - The pelvic congestion syndrome has been widely studied in the female sex, while
      there are not many publications on the male equivalent. Prostatitis represent the
      most frequent affections of the genito-urinary male tract that require the
      urologic consult, but in the majority of the cases the etiology of such
      affections remains unknown. Some forms of microscopic hematuria or macroscopic
      hematuria are also cryptogenetic. Varicocelectomy is widely given in the
      infertile patients, but not always the intervention achieves a recovery of the
      semen quality. In this work we revisit the anatomy of the pelvic male venous
      drain and we depict its objective findings with the echo-color-Doppler sonography
      (ECD). The purpose of the study is to encourage a polycentric uro-andrologic
      search on large numbers, with the goal of resolve if the ECD pictures of
      congestion pelvic syndrome could have relation with some "prostatitis syndromes",
      with some cryptogenetic hematuria and/or with the prognosis of the infertile
      patients undergone to varicocelectomy.

PMID- 12508724
TI  - [Echo-dynamic study of female urinary incontinence: our experience with the use
      of tridimensional ultrasonography].
AB  - Traditional 2-D ultrasound is a fast, inexpensive, non-invasive procedure and may
      be used routinely for the pre and post-operative evaluation of patients with
      various grade of cystocele, but a new tool in ultrasound investigation is
      recently available: the 3D scan. Our aim is to assess the real usefulness of 3D
      scan in the evaluation of cystocele grade. 15 women with clinical and urodynamic
      findings of genuine stress incontinence and grade 2-3 cystocele (in accord to
      Baden-Walker grading) underwent both ultrasonographic 3D imaging and traditional
      2D trans labial scan with Convex probe (3.5 Mh). Correct evaluation of the
      relationships between the bladder, urethrovesical junction, urethra and pubic
      bones at rest and when straining was correctly evaluated by 2D scan in all the
      women underwent the examination, whereas 3D scan did not let us exactly quantify
      the same anatomical defect. 3D ultrasound did not prove to be as useful as
      traditional trans-labial 2D ultrasound procedure to provide an objective
      demonstration of the mobility of the urethrovesical junction. A possible
      explanation is that the lack of reliability of 3D investigation is due to the
      impossibility of real-time scanning that make approximate the choice of the image
      to evaluate. In conclusion traditional ultrasound is up to now an important
      complementary evaluation for the study of female urinary incontinence which
      allows not only morphological documentation but can also improve our knowledge of
      function and anatomy of lower urinary tract. Finally it is basic to stress that a
      worldwide standardisation will be the starting point for the real success of this
      technique and, especially for the new 3D scan, it will be important to achieve
      this goal together a large amount of data to compare for defining the real
      importance of this investigation.

PMID- 12508725
TI  - [Imaging of the prostate: traditional methods].
AB  - Transrectal prostatic ultrasonography is an inexpensive, non-invasive procedure
      which permits an accurate evaluation of the dimensions and echostructure of the
      prostate and seminal vesicles. Prostatic tumors may present as hypoechogenic (60
      80%) or isoechogenic nodules (30%), the latter requiring the use of specific
      techniques, which increase the sensitivity and specificity of the procedure
      (contrast-enhanced color-power Doppler), to identify and characterize focal
      lesions. The color Doppler increases the predictive value of TRUS (62-75%) but
      has a low sensitivity, while the power Doppler enables us to study vessels with
      slow blood flow. The recent introduction of contrast medium could lead to an
      enhancement of the Doppler signal, thus increasing sensitivity of the exam; it is
      also, however, an expensive, invasive and time-consuming method. Improved test
      sensitivity has also increased the problems relating to the identification of
      very small prostatic lesions which are probably of low clinical significance.

PMID- 12508726
TI  - [Imaging of the prostate: three-dimensional ultrasonography].
AB  - Owing to its particular anatomic position, the prostate gland is an ideal organ
      for 3D ultrasound (US) study. However, although current US devices provide a
      large amount of information on the organ, they suffer from the limits of 2D
      imaging devices, as they cannot demonstrate the coronal plane. The latter plane
      shows details that could not otherwise be assessed; in fact, the central zone can
      only be viewed from the front, where it is also possible to visualize the course
      of the ejaculatory ducts and their outlet in the veru-montanum region. The high
      definition imaging power is also the reason why 3D US scanning provides a
      particularly reliable estimate of the prostate volume. The practical advantage of
      correct measurement of the organ volume, in toto or of particular suspicious
      areas, is that it enables better planning of both medical and surgical treatment.
      3D US can also overcome the difficulties encountered with traditional transrectal
      US in performing local tumour staging. The presence of an extra plane can clarify
      the relationships between the tumour and healthy prostate tissue, in the capsula
      as well. Precise visualization of the whole course of the ejaculatory ducts
      enables individuation of any tumour invasion, the first step towards identifying
      invasion of the seminal vesicles, that has a distinctly unfavourable prognosis.
      The vesiculo-prostatic angle is also easier to see and investigate. 3D US seems
      also to have a role in procedures for the diagnosis of prostatic carcinoma. Some
      important studies have shown a greater incidence of tumours identified in the
      transition zone if biopsy is conducted by guided 3D US rather than the usual 2D
      US. This method is also indicated in cases requiring dynamic assessment of
      prostate lesions, preparatory to excision or brachytherapy (precise positioning
      of the radioactive seeds) as alternatives to traditional surgery.

PMID- 12508727
TI  - [Imaging of the prostate: when should CT and MR be used?].
AB  - CT and MR imaging of the prostate. Both CT and MR imaging are employed in staging
      adenocarcinoma of the prostate. This article reviews the current status of these
      imaging modalities and describes emerging imaging technologies that may improve
      the diagnosis and staging of prostate cancer.

PMID- 12508728
TI  - [Imaging of the prostate: ultrasonography contrast media].
AB  - This article describes the main characteristics of ultrasound contrast media,
      their pharmacodynamic properties and their effect on various ultrasound imaging
      techniques. Contrast-enhanced TRUS is useful for improving the detection of
      prostatic cancer.

PMID- 12508729
TI  - [Response to a cognitive questionnaire on the guideline project of prostatic
      biopsy of the SIEUN--GUONE--SIUrO--SIBioC].
AB  - Ultrasound guided systemic sextant needle biopsy of the prostate is the procedure
      of choice for the diagnosis of prostate cancer. During the past 50 years, the
      techniques, indications, and pathologic interpretation of prostate biopsies have
      evolved. Moreover, the indications for prostate biopsy have become more refined.
      This paper provides the results of an interactive questionnaire on ultrasound
      guided biopsy of the prostate. 14 questions have been selected. A range of 102
      109 answers have been collected for every questions at Castrocaro (Fo) during the
      14th National Congress of the Italian Society of Urological, Andrological and
      Nephrological Ultrasound on May 3rd 2002.

PMID- 12508730
TI  - Intraoperative localisation and management of renal calculi during
      nephrolithotomy by real-time ultrasonography.
AB  - OBJECTIVE: To evaluate the role of ultrasound as a sole procedure for
      intraoperative localisation and management of complex renal calculi. MATERIAL AND
      METHODS: Between September 1997 and November 2001, 16 patients underwent complex
      surgery for multiple, large or recurrent renal stones using the ultrasound image
      as a the sole intraoperative diagnostic procedure. A 8.5 MHz sector transducer
      with a pulse Doppler signal was used to identify the avascular area, the shortest
      distance between the renal surface and the stone. RESULTS: Complete stone removal
      was achieved in all patients without complications. CONCLUSION: Intraoperative
      sonography for localisation of the intrarenal arteries combined with B scan
      sonography for intraoperative localisation of stones allows complete removal via
      radial nephrotomies without peduncle clamping and cooling procedure. The
      advantage is the exact and quick localisation of stones avoiding X-ray.

PMID- 12508731
TI  - [Long-term follow-up of peripelvic renal multicystic lymphangiectasia].
AB  - Renal peripelvic multicystic lymphangiectasia is a benign disease characterized
      by multiple cysts arising from the lymphatic vessels of the renal sinus. Cysts,
      almost always bilateral, surround the profiles of the calices; the biggest cysts
      can compress pelvis or iuxtapielic ureter and it is difficult to differentiate
      RPML from hydronephrosis at the Ultrasound. Cysts are asymptomatic, the profiles
      of calices appear irregular with thin membrane separating each other, the
      cortical of the kidney is preserved: these are principle elements to distinguish
      RPML to hydronephrosis at the Ultrasound. Usually it is necessary to confirm the
      diagnosis at IVP and CT scan evaluation. From 1995 to March 2002, 10 cases of
      RPML with a long-term follow-up have been studied. IVP in 8 patients and CT scan
      in 2 have shown compression of the collecting system by multiple cysts. We
      followed the cases with periodic lab tests of kidney function, ultrasound, IVP,
      CT scan. In order to valuate the presence of "true obstruction", we tested in
      over-night urine EGF and MCP-1 as markers of urinary tract obstruction and
      subsequent renal damage. A valuable data regarding how to differentiate RPML from
      hydronephrosis at Ultrasound show that RPML does not modify renal function and
      cyst volume has not changed in the time. In long-term follow-up the prognosis of
      the RPML is not clear. Particolarly this renal sinus disease has not neoplastic
      degeneration and the effect of cysts on kidney function is unknown. RPML is an
      uncommon disease and it can be enclosed in the group of renal sinus pathologies.
      The absence of symptoms, the hystologic diagnosis, the unchanged dimensions of
      the cysts confirm the benign prognosis of RPML which does not need a close
      functional and morphologic monitoring in the long-term follow-up.

PMID- 12508732
TI  - [Comparison of renal ultrasonographic and functional biometry in healthy patients
      and in patients with chronic renal failure].
AB  - OBJECTIVE: The purpose of this study, that examined healthy adult subjects and
      nephropatic patients, was to detect some relations between kidney's sonographic
      dimensions and renal function, expressed by creatinine clearance to evaluate more
      significant and useful sonographic parameters for the follow-up of nephropathies.
      SUBJECTS AND METHODS: Age, sex, body weight, height, body mass index, creatinine
      clearance were evaluated in 15 healthy and in 32 nephropathic subjects. In those
      subjects length, width, and thickness of the kidney and its central echogenic
      area and the parenchimal thickness of the upper pole were measured by
      ultrasonographic technique. Measurements were made with the patients in
      supine/oblique position. Renal shape index, parenchimal volume of the kidney and
      volume of the central echogenic area were calculated. Renal dimensions were
      correlated with age, total body area, body mass index and creatinine clearance.
      The patients, according to creatinine clearance, were divided into three classes:
      Class 1 Creatinine Clearance > 70 ml/min Class 2 Creatinine Clearance > 30 < 70
      ml/min Class 3 Creatinine Clearance < 30 > 10 ml/min RESULTS: The renal length,
      as renal failure progressed significantly decreased until creatinine clearance =
      30 ml/min. In class 3 the renal volume and the transvers diameter decreased as
      renal failure progressed. The renal parenchymal volume as renal failure
      progressed significantly decreased. Our results demonstrated that renal length
      reduced inside the three classes of patients but the reduction was significant
      only between the first and the second classes of patients. The transverse
      diameter and the renal shape index did not reduce significantly inside three
      classes of patients. The renal parenchimal volume reduced significantly inside
      the 3 classes. CONCLUSIONS: The more important measurement of renal size is
      longitudinal diameter in subjects with normal renal function. However, the renal
      parenchimal volume is the more exact sonographic parameter in end-stage renal
      failure.

PMID- 12508733
TI  - [Role of directional power-Doppler in the identification of renovascular
      malformations].
AB  - OBJECTIVE: The directional power-Doppler (dPD) is a useful tool in evaluating the
      renal vascularization for its high sensibility and availability. Renal vascular
      malformations like the arteriovenous fistulas (avF) are rare and their real
      incidence is unknown. We evaluated the diagnostic role of dpD in renal avF.
      MATERIAL AND METHODS: From January 1999 to 2002 1518 subjects (875 males, 643
      females, mean age: 62 years, range: 22-87 years) have been studied by both B-mode
      ultrasound and by dpD. All ultrasonographies were taken with a Toshiba Power
      Vision 6000 by the same skilled operator. RESULTS: Among 1518 patients examined,
      17 avF have been identified (diameter range: 3-18 mm) by using dPD. Four of these
      have an unclear etiology (congenital?) and they have been considered idiopathic.
      On the contrary, five are acquired: two are caused by renal biopsy, two by renal
      tumors and one by ureteral stent positioning, respectively. Eight patients, all
      affected by polycystic kidney disease, showed multiple avF. The four subjects
      with idiopathic avF are suffering from chronic renal failure (CRF--CrCl = 8-35
      ml/min); on the contrary, among patients with polycystic kidney, five of them are
      on CRF (CrCl = 14-27 ml/min), three have normal renal function. The acquired avF
      caused by renal biopsy or by ureteral catheterization have spontaneously
      disappeared after 15-20 days from the causative event. CONCLUSIONS: The dPD
      allows to individualize the arteriovenous malformations of renal vasculature
      which could be underestimated or not evidenced by other instrumental methods.

PMID- 12508734
TI  - [Aspiration versus aspiration plus ultrasonography-guided alcohol administration
      for simple renal cysts: recurrence and complications].
AB  - In this study the results of two percutaneous treatment of simple renal cysts are
      compared: aspiration alone versus aspiration and ethyl alcohol injection. Out of
      40 patients, 17 have been treated with aspiration only and 23 with aspiration and
      ethanol injection. Recurrent disease has been observed in 88.2% of patients in
      the aspiration group and 30.4% in the aspiration and ethanol injection group.
      This difference is statistically significant as shown by the Kaplan-Mayer curve
      when evaluated by the Log-rank test, and this is sufficient to justify such
      treatment as a first quality choice.

PMID- 12508735
TI  - [Doppler color ultrasonography in the assessment of double kidney
      transplantation].
AB  - OBJECTIVE: In our Transplant Centre, in the last three years, twelve patients
      with chronic kidney disease underwent a "double kidney" transplant according to
      Masson technique. Our purpose is the evaluation of ultrasonography and echo
      colorDoppler ultrasound in the diagnosis of possible clinical and surgical
      complications of "double kidney" transplant. PATIENTS AND METHODS: The "double
      kidney" transplant inclusion criteria are the following: donor age > 70 yrs;
      glomerulosclerosis > 20%; histological score (according to Kandinsky) > 4 and <
      6. In our centre, from January 1998 to December 2001, we made 68 kidney
      transplantations from marginal donors, 12 of them were "double transplant". Mean
      donor age was 74.3 +/- 5.3 (70-82). Renal function was determined by detection of
      serum creatinine; every single patient underwent to ultrasonography evaluation of
      grafts during follow-up. RESULTS: Mean follow-up is 10 +/- 4.6 months (6-18);
      mean value of donor's serum creatinine 1.5 +/- 0.6 mg/dl. Delayed Graft Function
      (DGF) rate was 50%; no case of Primary Non Function (PNF) and Acute Rejection was
      found. Patients with DGF (group A) had a Resistance Index (IR) > 0.80 (mean
      0.82); patients without DGF (group B) had an IR < 0.80 (mean 0.68 and 0.65) (p <
      0.05). All patients underwent an eco colorDoppler evaluation after 3 and 6
      months; in both groups (A and B) IR was, respectively, 0.75 and 0.71. Surgical
      adverse events were 41.6% (5/12): 3 urinary obstructions; 1 thrombosis of renal
      vein; 1 pelvic lymphocele. In all these patients the first diagnostic step was
      ultrasonography. Ultrasonography, in "double transplant" as in single one, have a
      very important role in post-transplant evaluation of DGF and surgical
      complications.

PMID- 12508736
TI  - [Nephrologic diagnosis besides ultrasonography: which other imaging methods?
      Guideline on the use of radiologic methods].
AB  - The present paper represents an overview of the imaging methods which could
      integrate the first ultrasonographic approach to nephrologic diagnosis. It
      summarizes the clinical indications and the appropriate imaging protocols
      including conventional radiology, CT, MR and Nuclear Medicine in five different
      clinical scenarios: reno-vascular hypertension, hematuria, acute pyelonephritis,
      acute and chronic renal failure, and acute urinary colic.

PMID- 12508737
TI  - [Testicular microlithiasis: unusual ultrasound finding].
AB  - OBJECTIVES: In our work we evaluate the incidence of testicular microlithiasis
      (TM) on more than 500 scrotal echoes we performed in our hospital in a period of
      three years, from 1998 to 2001. MATERIALS AND METHODS: Ultrasound sonography
      (USS) was performed by a 5.5-7.5 double scanned Mhz probe (Ansaldo AU 560
      degrees). RESULTS: We found only 2 cases of TM (0.4%); our percentage of such
      pathology is lower when compared to percentages we can find in literature. In
      only one case we performed a testicular biopsy, because the patient had
      teratospermia; we found intra tubular seminific calcification associated with
      haematoxilim positive bodies. DISCUSSION: Testicular microlithiasis has an
      echographic characteristic appearance, more than a clinical pathological issue.
      Referred literature shows how this pathology can be associated with
      criptorchidysm (20%) and can correlate (40%) with probability of clinical
      evolution in testicular malign neoplasms, mainly germinal ones. This pathology is
      characteristic in its showing multiple microcalcification, (not less than for
      testis), 1-3 mm in diameter and not always regularly distributed in testis
      parenchyma. Often associated with testicular microlithiasis is dyspermia.
      CONCLUSIONS: In patients in which microlithiasis of the testis is diagnosed, USS
      and bio-humoral follow-up is of major importance. Literature shows how high can
      be the risk that this pathology can evolve to germinal tumor. It must be
      recommended regular evaluation of alpha-fetoprotein, beta chronic gonadotropin.
      USS must be performed almost once a year. Biopsy is rarely suggested, and only in
      case of teratospermia. At the moment no therapy is referred.

PMID- 12508738
TI  - [Role of prostaglandin E1 determination in dynamic penile Doppler color
      ultrasonography: retrospective study of 900 patients].
AB  - Eco colorDoppler flowmetry greatly increased the knowledge about penile erection.
      This diagnostic tool enables the study of arteriogenic erectile failure. We
      report on our six-year experience with this procedure on 900 men with erectile
      dysfunction. This experience lead us to standardise the method utilising high
      doses (20-40 micrograms) that minimise false negatives.

PMID- 12508739
TI  - Dyspermia and testicular artery peak systolic velocity.
AB  - OBJECTIVE: To compare reliability of peak systolic velocity (PSV), end diastolic
      velocity (EDV), resistivity index (RI) of testicular arteries,
      folliculostimulating hormone (FSH) and testicular volume in the differential
      diagnosis of dyspermias. PATIENTS AND METHODS: Testicle volume, FSH, PSV, EDV,
      and RI were compared with analysis of variance among the following patients or
      controls: 9 obstructive azoospermic (OA), 20 non obstructive (NOA), 17
      oligoasthenospermic varicoceles + male accessory glands inflammation (MAGI), 38
      undetermined oligoasthenospermic, 19 MAGI, 11 varicoceles, 32 subjects with
      normal sperm analysis who recently fathered (fertile controls), and 15 subjects
      with normal sperm analysis with varicocele who recently fathered. RESULTS: Only
      PSV and RI proved to be selective for the different classes of patients, while
      EDV, FSH and testicle volume did not. Varicoceles, varicoceles + MAGI and fertile
      varicoceles showed the highest PSV and RI; fertile controls, OAs and MAGIs
      displayed similar PSV and RI; undetermined patients displayed significantly lower
      PSV and RI, NOAs' PSV and RI proved to be the lowest. CONCLUSIONS: RI and PSV
      proved to be a reliable tool to be routinely used in the clinical study of
      infertile/dyspermic males, whereas EDV, FSH and testicle volume did not.

PMID- 12508740
TI  - [Significance of scrotal Doppler color ultrasonography in the postoperative
      control of patients treated with varicocelectomy].
AB  - ColorDoppler Ultrasound (CDU) is one of the principle methods in the post
      operative diagnosis of recurring varicoceles. Aim of this study was valuate
      modifications of seminal parameters related to scrotal CDU results. In order to
      clarify varicoceles effect on fertility, these parameters have been related to
      pregnancy rate. We have studied 93 patients with varicoceles, undergone to venous
      "en bloch" legature from november 1994 to december 2000. Recurrence rate was 3.1%
      at post-operative scrotal CDU after 3 months. In patient with negative CDU,
      seminal quality improved (statistically significant results) and pregnancy rate
      was 41.4%. CDU has an important role in varicoceles, both at diagnosis and in
      post-operative follow-up. It is a quick and simple test, non-invasive and well
      tolerated by patients. If associated with spermiogram, it is useful in order to
      show post-operative recurrences and surgical complications in patients treated
      with varicocelectomy.

PMID- 12508741
TI  - [Adenomatoid tumor of the epididymis. Ultrasonographic diagnosis and review of
      the literature].
AB  - Epididymal adenomatoid tumor is a rare genital neoplasm of mesotelial origin.
      OBJECTIVES: In our work we show our experience about three cases of epididymal
      adenomatoid tumor we observed in four years. We describe our clinical experience
      in which these cases seem to be peculiar for clinical insurgence and
      localization, mainly, in our clinical report, on the head of epididymis. A review
      of few cases reported in literature is presented above. MATERIALS AND METHODS: In
      a period of four years we evaluated more than 600 scrotal echoes. Ultrasound
      sonography was performed by a 5.5-7.5 double scanned MHz probe. RESULTS: USS of
      the scrotum revealed, in two cases, an anechoid-hypoechoid mass, localized on the
      epididymal tail. One patient was admitted to the hospital with clinical symptoms
      of acute torsion of the testis, but no torsion was found at surgical examination.
      The gross examination, in every cases, showed a nodular, tight, encapsulated
      mass, with yellowish and homogeneous cut surface. DISCUSSION: Epididymal
      adenomatoid tumor is a rather rare form of benign neoplasm of genitalia. This is
      deducted from the rare cases reported in the literature. The origin of that
      neoplasm is controversial. The main hypothesis is, nowadays, that these tumors
      could arise from mesemchima. Epididymal adenomatoid tumor is a neoplasm mostly
      reported in young patients. USS is always of main importance to permit a pre
      operatory differential diagnosis with malignant tumors of the testis. It shows,
      in facts, characteristical echo patterns that permitted, in all cases, a
      conservative surgery, with direct access through the scrotum. CONCLUSIONS: Our
      experience shows the mainly importance of USS in differential diagnosis between
      scrotal masses. Characteristic echo pattern permits overall sure rapid surgical
      access and a conservative approach.

PMID- 12508742
TI  - [Percutaneous treatment of varicocele: considerations and our experience].
AB  - Due to its high incidence and its affecting male infertility, varicocele is an
      important disease. Consequently, it is essential to choose the best treatment.
      MATERIALS AND METHODS: Since 1999 to 2000, 75 patients affected by varicocele
      (mean age 25 years) underwent percutaneous retrograde sclerotherapy through a
      right transfemoral approach. Pre-operative tests included physical examination,
      sperm analysis and colour Doppler sonography. According to Dubin and Amelar
      classification, 59% of patients were affected by Grade 3 varicocele. According to
      Hirsh classification, grade III-IV varicocele was diagnosed with colour Doppler
      sonography in 77.3% of patients. Mean operative time was 30 minutes with only 5
      minutes of exposure to radiation. All patients were followed-up with colour
      Doppler ultrasound and sperm analysis 1, 4 and 12 months after the treatment.
      RESULTS: In 6 of 75 patients (8%) sclerotherapy was unsuccessful because it was
      not possible to catheterize the spermatic vein. No significant complications were
      observed pre and post-operatively. 3 patients complained of mild testicular pain
      and 1 case had a transient hydrocele. The patients were dismissed during the next
      24 hours after the procedure. During follow-up, physical examination was
      unremarkable in all patients, while occlusion of spermatic veins showed by
      Doppler ultrasound at 4 and 12 months was achieved in 94% of patients.
      CONCLUSIONS: Retrograde sclerotherapy through trans-femoral approach is a safe
      and effective treatment. In our opinion it should be considered as the treatment
      of choice, especially if we consider the costs, hospitalization and complications
      of conventional surgery and laparoscopy.

PMID- 12508743
TI  - [Role of power Doppler in the differential diagnosis between organic and
      functional cavernovenous insufficiency in patients with erectile maintenance
      deficiency].
AB  - Dynamic penile eco colorDoppler (ECDP) shows limits of specificity in case of
      differential diagnosis between functional (adrenergic hypertone) and organic
      cavernovenous incompetence. The aim of this study is the evaluation of a new flow
      chart for venogenic erectile dysfunction diagnosis, including power Doppler (PD),
      avoiding the repetition of ECD with higher concentrations of PGE1. In fact this
      procedure is invasive, often painful and burdened by a consistent risk of
      priapism. Patients suspected of caverno-venous incompetence underwent PD during
      the ECD. 85 of them showed high telediastolic velocity but normal systolic peak
      flow. All these patient underwent PGE1 redosing, to a maximum of 40 micrograms.
      Patients with still suspicious ECD were administered RigiScan. 63 patients over
      85 had good PD, while 22 had bad PD. Of the 63 patients with good PD, 60 (95%)
      had normal ECD after redosing, while in 3 (5%) of them the telediastolic velocity
      remained high. In these 3 patients RigiScan showed normal nocturnal rigidity in 2
      cases, abnormal in 1. 18 patients (82%) of the 22 with bad PD never showed
      improvement of ECD and RigiScan resulted altered in 15. In our opinion
      concordance between 10 micrograms ECD and PD avoids redosing in demonstrating
      organic venogenic erectile dysfunction. If PD is good but ECD is altered, 10
      micrograms re-dosing could help in differentiating organic or functional erectile
      dysfunction. The diagnostic flow chart, then, should always include PD.

PMID- 12508744
TI  - [Transperineal ultrasonography versus cystography in urinary incontinence].
AB  - The aim of this study is to evaluate diagnostic accuracy of perineal ultrasound
      versus cystography in patients affected by urinary incontinence (UI). 40 patients
      affected by UI were evaluated by voiding cystography and by perineal ultrasound
      through sagittal scans. Bladder floor related to public simphysis, urethro
      vesical angle, bladder neck dilatation after an increase of abdominal pressure
      with or without urine leakage, were checked. The comparison with urinary
      cystography gave similar results. In our experience perineal ultrasound study of
      pelvic floor showed, in the evaluation of urinary incontinence, the same accuracy
      of the urinary cystography. Ultrasound study allows a good visualization of the
      anatomic structures of the pelvic floor and of the lower urinary tract and a good
      evaluation of the tissues; it also offers easy performance, low cost, less
      invasivity and a better compliance.

PMID- 12508745
TI  - [Incontinence after retropubic radical prostatectomy: correlation between
      ultrasonographic morphological data and urodynamic parameters].
AB  - OBJECTIVE: The aim of this study is to evaluate the relationships existing
      between transrectal ultrasound and urodynamics in patients undergone radical
      retropubic prostatectomy and affected by stress incontinence. MATERIALS AND
      METHODS: 78 patients were suitabe for the study. They have been divided in three
      groups: group A, 18 incontinent patients (at least 1 pad a day); group B, 30
      patients with occasional dribbling (no incontinence device needed); group C, 30
      continent patients. All the patients have undergone urethral pressure profile
      (UPP), abdominal leak point pressure (ALPP) and transrectal ultrasound (TRUS).
      ultrasound has been performed injecting saline solution in the spongious and
      bulbar urethra to dilate it and better visualize a collapsed tract corresponding
      to the distal sphincter, that was measured. Different doctors performed TRUS and
      urodynamics, and each ignored the results of the other tests. RESULTS: The mean
      value of TRUS length of the collapsed urethral segment was 5.47 mm (range 4.9
      6.0) for group A, 11.5 mm (9.5-12.9) for group B, 13.8 mm (10.4-14.7) for group
      C. the mean value of rest FUL was 36.6 (range 23-52) for group A, 31.7 (range 21
      37) for group B, 13.8 (range 10.4-14.7) for group C. The mean value of stress FUL
      was 20.3 (range 5-29) for group A, 20.7 (range 18-27) for group B, 25.0 (range 20
      35) for group C. The mean value of VLPP was 61.9 cm H2O for group A, 83.6 cm H2O
      for group B, > 90 cm H2O for group C. CONCLUSIONS: The ranges of values of VLPP
      were narrower and showed less overlap among the groups than UPP. TRUS length
      showed a good correlation with VLPP and permitted to differentiate incontinent
      patients from continent patients and patients with occasional dribbling. These
      data correlate well with the possible role of the length of the urethral stump
      and of damage to genitourinary diaphragm in post-prostatectomy incontinence.

PMID- 12508746
TI  - [Ultrasonographic assessment of bladder volume].
AB  - INTRODUCTION: The aim of this study is to evaluate intra and inter-observatory
      variability in the sonography measurement of bladder volume. MATERIALS AND
      METHODS: We have evaluated 138 patients (128 men and 10 women) affected by lower
      urinary tract symptoms with a mean age of 64 years (range 36-75) between December
      2000 and June 2001. Sonography measurement of bladder volume was obtained at the
      end of a pressure/flow study with the double lumen catheter in situ. Measurement
      of bladder volume was performed by the same operator in 113 patients by
      calculating the transverse, longitudinal and anterior-posterior diameter; each
      measurement was repeated three times. In the remaining 25 patients examination
      was performed by three different operators for every patients, with a single
      evaluation for each operator. The real volume was measured by emptying the
      bladder using the urethral catheter. RESULTS: The real bladder volume in the
      intra and inter-observatory group was 240 +/- 130 and 145 +/- 97, respectively.
      First, second and third measurement in the intra-observatory group were 229 +/-
      113, 231 +/- 112, 234 +/- 127, respectively. On the other hand, first, second and
      third measurement in the inter-observatory group were 131 +/- 73, 129 +/- 66, 143
      +/- 94, respectively. CONCLUSIONS: Looking at our results, it is clear that there
      is no significant difference between every single measurement in the intra and
      inter-observatory group. In addition, the estimation of bladder volume by
      ultrasound was quite similar to the real volume. We conclude that ultrasound is a
      precise, non invasive and highly reproducible technique to calculate the bladder
      volume.

PMID- 12508747
TI  - [Severe hypoglycemia caused by sulfonylureas and biguanides in a patient with
      obstructive anuria: resolution with ureteral stent].
AB  - We report about a single kidney patient affected by a critical hypoglycemia due
      to acute renal failure in obstructive uropathy whilst receiving sulfonylureas and
      biguanides for diabetes. Clinical picture was successfully treated by
      endoureteral lithotripsy and placing a double j catheter.

PMID- 12508748
TI  - [Ultrasonography-guided transrectal perineal drainage of retroanastomotic
      collections in orthotopic neobladder].
AB  - Pelvic collections are not an uncommon complication of pelvic surgery. Usually,
      such a complications are managed by TC-guided percutaneous drainage or even by
      more invasive surgical operations. Here, we describe a transperineal TRUS-guided
      drainage technique of pelvic urinomas occurring after a radical cystectomy (RC)
      for invasive Bladder Cancer (BC) in two patients, respectively 55 and 77 YOM.
      Respectively, 10 and 20 days after catheter had been taken out patients began
      complaining a severe pelvic pain associated to fever (over 40 degrees C).
      Physical examination and an ultrasound, followed by a CT-scan, showed a huge
      retroanastomotic pelvic urinoma (width over 10 cm). CT-guided percutaneous
      drainage was considered at increased risk of iatrogenic injury of mesenterial
      neobladder because of its location. A TRUS-guided percutaneous perineal drainage
      of urinomas with a pig-tail 8 ch was carried out. Urinomas were successfully
      drained and no significant complications were encountered. At a median follow-up
      of 11 months no late complications were found. Our preliminary experience with
      this procedure is favourable regarding mininvasivity, lack of complications and
      its feasibility by urologists themselves. Its impact on cost/benefit rate is
      favorable too. We believe that this technique might be considered as an
      alternative to CT-guided percutaneous drainage.

PMID- 12508749
TI  - [Role of ultrasonography-guided prostatic biopsy of hypoechoic areas associated
      with systematic biopsies in patients with normal and high PSA levels].
AB  - OBJECTIVE: The aim of the study is to evaluate the need to perform directed
      biopsies to hypoechoic areas at transrectal ultrasound associated with a
      prostatic mapping in patients with normal and elevated levels of PSA. MATERIALS
      AND METHODS: Since January 1987, 517 consecutive patients (mean age: 65.5 +/- 5.2
      yrs) underwent selective prostatic biopsies of hypoechoic areas and systematic
      sextant biopsies with 10 samples in patients with a prostatic volume < 60 g and
      12 samples in prostatic volume > 60 g. RESULTS: The median PSA value was 7.2 +/-
      4.6 ng/ml (SD). 52% of the patients had a positive digital rectal examination.
      Cancer was detected in 47% of the patients (245/517), in 18% (14/78) of patients
      with PSA level < 4.0 ng/ml, in 42% (109/256) with PSA level from 4 to 10 ng/ml,
      in 66% (122/183) with PSA > 10 ng/ml. The PSA value was statistically higher (PSA
      = 14.9 +/- 17) in patients with positive prostatic biopsies compared to patients
      with negative biopsies (PSA = 8.5 +/- 8.3 ng/ml) (p > 0.0001). The PPV (positive
      predictive value) of the hypoechoic lesions was 36% (187/517). Cancer was
      detected only in directed biopsies of the hypoechoic areas regardless of PSA
      value in the 20% of patients (49/245). Sextant biopsies were positive with
      negative directed biopsies in 24% (58/245) of the patients, while both directed
      and sextant biopsies were positive in 56% (138/245) of the patients. COMMENTS:
      The hypoechoic lesion is the prostatic area in which prostatic cancer is most
      likely to be located in spite of the fact that the PPV of a hypoechoic area is
      less than 40%. The combination of sextant and lesion-directed biopsies maximizes
      the detection rate using the lowest possible number of biopsy cores. In the case
      of a TRUS visible lesion, the optimal number and placement of added systematic
      biopsies is yet to be defined. Due to the multifocality of prostate cancer, in
      the future, it is probable that, by adding more biopsies to the sextant standard
      scheme, the necessity of biopsying single small hypoechoic lesions will no longer
      be necessary.

PMID- 12508750
TI  - [Prostatic tumor: how many biopsies?].
AB  - INTRODUCTION: Ultrasound-guided prostatic biopsy is usually performed by sextants
      according to Hodge, but the authors feel that 6 biopsies are insufficient. It has
      been suggested that the number of prostatic biopsies be increased and the mapped
      areas extended, but this causes discomfort to patients and increases effective
      costs. The authors suggest repetition of biopsies in "risk" cases, routinely
      selecting patients taking into account the best cost-benefit ratio. MATERIALS AND
      METHODS: From January 2000 to December 2001, 682 first series biopsies were
      performed on as many patients. A Stamey modified sextant technique was used: 6
      biopsies, 3 on each side carried out more posterolaterally than the original
      technique. The biopsy procedure was repeated within 4 months in 11 patients with
      high risk clinical parameters (PSA > 10 or high PSA and prostatic nodule). During
      the period of observation, 25 patients had over 0.75 ng/year increase in their
      PSA and so biopsies were repeated. RESULTS: After the first biopsy series, 277
      were positive. Of the 11 repeated biopsies, 3 were positive. Of the 25 patients
      with altered PSA velocity, 9 were positive. DISCUSSION AND CONCLUSIONS: It has
      been shown that only 10-12% of biopsies are false negative in the sextant biopsy
      series when taken posterolaterally. The techniques that increase the number of
      biopsies have around 3-5% false negatives, but this involves more discomfort for
      the patient, local anaesthesia and a possible increase in complications. The
      procedure whereby biopsies were only repeated in patients with high risk clinical
      elements, saved 3852 biopsies from being carried out, with an economic saving
      (just on the histological exam that was not carried out) assessed at 59.681,80
      Euro (115,560,000 Lire) for our Local Health Service.

PMID- 12508751
TI  - [Tolerability to transperineal prostatic biopsy based on the number of
      specimens].
AB  - Prostate biopsy is a fundamental step in the diagnostic flow chart of prostate
      cancer. We have evaluated the influence of the number of cores taken on the
      tolerability and morbidity of the transperineal ultrasound-guided prostate
      biopsy. We have compared a group of 240 pts undergone 16 core prostate biopsy to
      an historical cohort of 100 pts undergone 10 core prostate biopsy. All the
      patients in both groups have been investigated about tolerability and morbidity
      of the procedure. No significant differences emerge between the two groups, and
      then we conclude that the number of cores taken does not influence the safety and
      compliance to the transperineal biopsy. This is a significant advantage compared
      to transrectal biopsy, as the number of cores influences the detection rate of
      prostate carcinoma.

PMID- 12508752
TI  - [Role of 3D-ultrasonography in the assessment of transitional zone PSA].
AB  - OBJECTIVE: Valute 3 TRUS to study the transitional zone of the prostate to
      calculate the PSA density Tz in patient with first negative biopsy, PSA Tot > 4
      ng/ml and clinical suspicion of cancer. METHODS: During a 12 months period we
      performed 429 biopsies. All patients had PSA = 4-10 ng/ml and/or suspected DRE.
      We repeated biopsy in 35 patients with PSA > 4 ng/ml, normal DRE but clinical
      suspicion of cancer. We used 3 TRUS to calculate the PSA density Tz and we
      performed standard sextant biopsies and additionally two biopsies of the
      transitional zone one on each side. RESULTS: Of the 429 patients, 304 (70.8%) had
      IPB, 100 (23.3%) had cancer in peripherical and/or apex zone, 25 (5.9%) cancer in
      the transitional zone only. CONCLUSIONS: The use of 3 DUS is very important to
      study and estimate the volume of the transitional zone to calculate the PSA
      density Tz. The clear visualization of the Tz permit a careful execution of the
      biopsy. The biopsy of the TZ is not a method for the early detection to cancer
      prostate but only for specifics cases: negative first biopsy, negative DRE, PSA
      Tot > 4 ng/ml and clinical suspicion of cancer.

PMID- 12508753
TI  - [Ultrasonography-guided transperineal prostatic biopsy: optimization of sampling
      protocol after 1,352 biopsies].
AB  - We report our experience-based approach in transperineal ultrasound guided biopsy
      to detect early prostate cancer. We selected patients on the basis of clinical
      characteristics. We tried to determine correct number and sites of biopsy to
      reduce patient discomfort and complications without loosing sensibility. Routine
      TZ biopsy increases detection rate of prostate cancer in T1 patients. Lateral
      peripheral biopsy resulted in a loss of sensibility of 5% and thus we considered
      it useless. Literature reported gain of sensibility with lateral peripheral
      biopsy referred to transrectal technique. Needle angle of incidence is different
      and therefore the area biopsied differs. Thus, results are not comparable.

PMID- 12508754
TI  - [Ultrasonography-guided transrectal prostatic biopsy: indications, methods,
      complications. Our experience].
AB  - There are more than one indications and management regarding the role of the
      prostatic biopsy. Multiple ultrasound guided transrectal prostatic biopsies have
      been immediately indicated to these patients with total PSA up to 10 ng/ml even
      if digital rectal examination have been negative. If total PSA from 4 to 10 ng/ml
      and PSA ratio in the gray zone, we first started with an antiflogistic therapy
      for 40 days. In the cases with total and ratio PSA levels u to the standard
      limits we performed ultrasound guided multiple prostatic biopsy. Normally we
      performing the biopsies in patient age not over 75 years old. Ultrasound
      procedure has been performed using an Siemens Sonoline ADARA with transrectal
      multiplanar 7.5 MKZ ultrasound probe 18 G per 20 mm automatic needle Bard kit. We
      using a ten biopsies mapping of the prostate: 6 biopsies on the right and left
      lobe, 2 biopsies on the transitional zone and 2 biopsies on the lateral side of
      the periferic prostatic tissue. Our experience suggests that ultrasound guided
      transrectal prostatic biopsy is a safe, well tollered and complication-poorly
      (6%) diagnostic procedure for the diagnosis of prostate cancer.

PMID- 12508755
TI  - [Transrectal prostatic biopsy with "end-fire" endovaginal probe].
AB  - OBJECTIVE: Sextant ultrasound-guided biopsy is still the standard way for the
      diagnosis of prostate cancer, although there have been several modifications. We
      report our experience using a 7.5 MHz endovaginal "end-fire" probe in patients
      undergoing prostate biopsy because of clinical findings suggestive of prostate
      cancer (abnormal digital rectal examination and/or elevated prostate specific
      antigen). MATERIALS AND METHODS: Since June 1999 to December 2001, we performed
      262 ultrasound-guided transrectal 18G core biopsies with a 7.5 MHz endovaginal
      "end-fire" probe, using different schemes according to the presence or not of
      suspicious areas on ultrasound (a modified sextant biopsies plus two cores from
      the transitional zone with multiple cores from and around suspected lesions in
      case of abnormal findings on ultrasound). RESULTS: We obtained a detection rate
      of about 44%. Complications were mild: 5 cases (1.9%) of urosepsis and 4 cases
      (1.5%) of urinary retention. Both haematuria and rectal bleeding were not
      significant. CONCLUSIONS: The endovaginal "end-fire" probe allows us to obtain
      core biopsies in both longitudinal and transverse view. This means an optimal
      sampling of the prostate gland, in particular a better and safer sampling of
      transitional zone avoiding the prostatic urethra and the choice of the best plane
      in order to sample more peripheral zone and its lateral aspects. Furthermore,
      with the "end-fire" probe it is quite simple to obtain cores biopsies from every
      portion of the prostate gland and, consequently, it is possible to make an
      accurate staging of the disease prior to surgery.

PMID- 12508756
TI  - [Role of transrectal ultrasonography in prostatic brachytherapy].
AB  - The rationale for interstitial brachytherapy (seed implant) is based on the
      principle that dissipation of radiation energy in tissues decreases exponentially
      as the square of source would receive maximal doses of radiation, there will be a
      rapid fall-off the dose in surrounding normal tissues. Over the years, a range of
      isotopes have been tested, and the technique have evolved from free-hand
      implantation to ultrasound guided template system. MATERIALS AND METHODS: From
      September 2001 to March 2002 we treated 17 patients with clinically localized
      prostatic cancer. For seed implantation we used the transrectal ultrasound guided
      implantation of 125I source. Isodose distributions are provided at each 5 mm
      increment throughout the treatment volume to determine the precise localization
      of seed placement. RESULTS: 23.5% of patients developed acute urinary retention,
      11.8% incidence of transurethral resection after 6 months and 0% incidence of
      urinary incontinence. Longer follow-up will be necessary for biochemical failure.
      CONCLUSIONS: Permanent interstitial implantation should be limited to patients
      with early stage disease with favourable prognostic features. The use of
      transrectal ultrasound as diagnostic system as guided implantation is the most
      popular approach even in experienced hands.

PMID- 12508757
TI  - [Morbidity, tolerability, and number of samples in prostatic biopsy: our
      experience].
AB  - Transrectal prostatic ultrasonography with biopsy is a fundamental step in the
      diagnosis of prostate cancer. The number of bioptic samples taken has a direct
      influence on the sensitivity of the diagnostic procedure. We compared the degree
      of acceptance of the biopsy, using visual analogue scale, with the appearance of
      complications in two groups of 250 patients: group A (sextant biopsy) and group B
      (traditional transrectal prostatic biopsy + 2 additional lateral samples from
      each lobe). 21% of group A patients reported slight pain, 63% tolerable pain and
      16% severe pain, while pain intensity of group B patients was 18%, 65% e 17%,
      respectively. The appearance and degree of painful symptomatology, and the
      frequency of serious complications were not significantly different in either
      group. The extensive prostatic biopsy is well tolerated by patients and is
      associated with modest local complications.

PMID- 12508758
TI  - [Ultrasonographic diagnosis of penile fracture].
AB  - Penile fracture is a serious urological condition that requires surgical repair.
      We report a case of a penile fracture after traumatic event where sonography was
      performed and demonstrated the exact site of the rupture in the tunica albuginea
      and the urethral integrity.

PMID- 12508759
TI  - [Role of prostate fossa ultrasonography in the diagnosis of local recurrence
      after radical prostatectomy in case of PSA failure].
AB  - OBJECTIVES: The aim of this study is to verify the diagnostic accuracy of
      transrectal ultrasound (TRUS) of vesico-urethral anastomosis in patients with PSA
      elevation (> or = 0.2 ng/mL) after radical prostatectomy, who received 4-6 random
      anastomotic biopsies of the prostatic fossa plus additional biopsies directed to
      TRUS detectable lesions. MATERIAL AND METHODS: Since 1992 up to now, 102 patients
      (mean age: 68.3 +/- 5.4 years) with PSA elevation after radical prostatectomy
      underwent TRUS of the vesico-urethral anastomosis and 4-6 TRUS-guided random
      biopsies plus 1-2 additional biopsies directed to TRUS detectable lesions.
      Pathologic stage was B (ASS classification) in 60% of cases, C in 36% and D in 4%
      (patients without hormonal treatment who underwent TRUS-guided biopsy because of
      TRUS detectable or palpable lesion). RESULTS: The mean PSA at biopsy time was 2.1
      +/- 4.6 (SD) ng/mL (range: 0.2-31.6 ng/mL) with median PSA of 0.9 ng/mL. DRE was
      positive in 37% of cases, while TRUS was positive in 73%. Recurrent
      adenocarcinoma was detected in 51% of all patients and in 45% (26/57) of patients
      with PSA < 1.0 ng/mL. TRUS sensitivity was higher (80%) than DRE (50%), but
      specificity was lower (37% vs 81%). The positive predictive value of TRUS
      detectable lesion was 60%. TRUS sensitivity and specificity increase with PSA
      elevation and sonographic aspects of prostatic fossa are statistically correlated
      with histology when PSA > 1.2 ng/mL. CONCLUSIONS: TRUS of the vesico-urethral
      anastomosis seems to be more sensitive but less specific than DRE for prostatic
      cancer local recurrence. More than half of TRUS detectable lesions is positive at
      biopsy. TRUS and TRUS-guided biopsy accuracy are directly correlated with PSA
      elevation.

PMID- 12508760
TI  - [Staging of prostatic carcinoma: TRUS prospective study versus endocoil MRI].
AB  - OBJECTIVE: Accurate staging of prostatic cancer is important for planning an
      optimal treatment, such as radical prostatectomy in clinical stage T2. About 40
      50% of patients operated for cT2 disease show a pathological stage T3 disease. In
      a prospective study we analysed accuracy of TRUS and endocoil MRI in a group of
      patients before radical prostatectomy. MATERIALS AND METHODS: 33 consecutive
      patients suspicious of prostate neoplasms were studied and staged with TRUS and
      endocoil MRI before prostatic biopsy and before radical prostatectomy. One
      urologist trained in TRUS conducted the exam, while one radiologist interpreted
      the MRI studies in a blind mode. The criteria evaluated were accuracy of global
      staging, extracapsular extension (ECE) and seminal vesicle invasion (SVI). These
      results were correlated with the histopathological findings after radical
      prostatectomy. RESULTS: The histopathological results showed 14 patients (42%)
      with pT2 disease, 18 patients (54%) with pT3 disease and 1 case (4%) of pT4
      disease. TRUS showed a low sensitivity (38%) and a good specificity (78%), with
      an overall accuracy of 50%; the best result was 96% specificity for SVI. Endocoil
      MRI showed a good sensitivity (70%) and specificity (76%), with an overall
      accuracy of 73%. Endocoilc was also useful to stage T1c disease when TRUS is
      negative. TRUS tends to understage, whereas endocoil MRI over-stages prostate
      cancer. CONCLUSIONS: TRUS and endocoil MRI may help in decision making about the
      appropriate treatment of prostatic cancer, even if they have limited current
      value, due to understaging or overstaging.

PMID- 12508761
TI  - [Acceptability and safety of transrectal prostatic 8-core biopsy].
AB  - The safety of sextant prostate biopsy has already been documented since the end
      of the 90's. As a higher efficacy of biopsy has been proved when increasing the
      number of samples taken, we have tried to assess the safety and tolerability of
      prostatic 8-core biopsy. From January to December 2001, 204 patients, aged
      between 50 and 88 (average 70) with a PSA between 0.74 and 196 ng/ml (10 +/-
      9.25), underwent in 8-core prostate biopsy. After biopsy, the patients were given
      an oral antibacterial for 3 days. After taking the samples, patients were
      interviewed about the tolerability of the biopsy, and especially about the
      following: I. A feeling of irritation (77 patients, 37.7%); 2. A slight pain (72
      patients, 35.29%); 3. A moderate pain (32 patients, 15.68%); 4. Intense pain (23
      patients 11.27%). After 20 days all patients came back and were interviewed again
      about possible complications (biopsy was Ca positive in 86 cases, 42.15%). 153
      patients (75%) reported a slight hematuria for an average period of 5 days; 88
      patients (43.13%) showed slight anal-rectal hematic discharges, mainly after
      defecation efforts. It was never necessary to hospitalize any patients because of
      complications. 71 patients (34.8%) reported a perineal pain which disappeared
      after 24-48 hours. 175 patients reported having had an ejaculation after biopsy
      and 158 (90.2%) of them showed hematospermia. 4 patients (2%) had a short period
      temperature and only 2 (0.98%) were hospitalized for hyperpyrexia with symptoms
      of genitourinary sepsis. It has been proved that TR prostate biopsy is almost
      exclusively followed by minor complications, major ones being an exception. A
      biopsy with more than six samples (8-10-12) shows a higher number of minor
      complications (hematospermia and hematuria). The fact that a higher number of
      samples proves this method to be significantly more suitable, pays off all the
      problems. Also, such a casistics makes us think that prostatic 8-core biopsy is
      generally well tolerated (73% of patients reported either irritation or slight
      pain) and fairly safe, as complications are mainly minor ones. We must therefore
      underline the suitability, good tolerability and safety of the TR prostatic 8
      core biopsy.

PMID- 12508762
TI  - [Thrombosis of perineal superficial venous vessels documented with
      ultrasonography].
AB  - Authors describe a rare subject of perineal superficial venous thrombosis in a 51
      years old patients.

PMID- 12508763
TI  - Not the Lucy, not the one.

PMID- 12508764
TI  - The "Braids Lady" of Arezzo: a case of rheumatoid arthritis in a 16th century
      mummy.
AB  - OBJECTIVE: To diagnose a probable case of rheumatoid arthritis in a mummified
      female body from the 16th century and to backdate the first clinical diagnosis,
      entering the diatribe regarding the ancientness of the disease. METHODS: Image
      techniques such as normal X-ray, X-ray by mammography, total body CT and high
      resolution CT were used. Microscopic examination by stereomicroscopy was
      performed. Samples of tissue were submitted to histology. These data and the
      review of past literary references, of artistic representations and of
      paleopathological cases provided an interesting contribution to reconstruct the
      history of the disease. RESULTS: The body of the "Braids Lady" showed all the
      "stigmata" of the disease. The left hand revealed large erosions of the
      metacarpophalangeal joints of both the third and the fourth fingers, volar
      metacarpophalangeal subluxation of both the third and the fourth fingers and
      lateral deviation of all the fingers. The carpus showed some minute and marginal
      erosions of the bones. The bases of the first phalanges were slightly flared. The
      toes showed partially overlapped fibular deflection. CT evidenced subluxations of
      the joints. The body showed no involvement of sacroiliac articulation.
      CONCLUSIONS: The "Braids Lady" was affected by rheumatoid arthritis. A large
      number of features typical of the disease were recorded. Differential diagnosis
      supported the findings. The death of the lady was established at the end of 16th
      century, namely 200 years before the first clinical diagnosis worked out by
      Landre Beauvais in the early 1800s.

PMID- 12508765
TI  - Regional cerebral blood flow and cytokines in young females with fibromyalgia.
AB  - OBJECTIVE: To determine whether there is any difference in regional cerebral
      blood flow (rCBF) and serum cytokine levels and association between clinical
      parameters and rCBF and serum cytokine levels in young females with fibromyalgia
      (FM). The other aim was to search whether the depression state has any effect on
      these two parameters. METHODS: Nineteen women with FM and 20 healthy women had
      99mTc-HMPAO brain single-photon-emission computed tomography (SPECT) to evaluate
      rCBF. Serum interleukin (IL) levels (IL 1 beta, IL 2r, IL 6 and IL 8) were
      measured. Clinical and psychological evaluation was also carried out in FM
      patients and healthy controls. RESULTS: The patients with FM had significantly
      higher radioactivity uptake ratio in right and left caudate nucleus (p = 0.009, p
      = 0.001, respectively) than healthy controls. There was statistically significant
      decrease in the 99mTc-HMPAO uptake in the right superior parietal (p = 0.041),
      gyrus rectalis (p = 0.036) and pons (p = 0.023). FM patients had significantly
      higher serum IL 2r and IL 8 levels (p = 0.023, p = 0.011, respectively) than
      controls. Additionally, FM patients had significantly higher Fibromyalgia Impact
      Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), and Hamilton
      Depression Rate scale (HDRS) scores (p = 0.000) than controls. Interestingly, the
      patients with mild depressive symptoms or without (i.e. HDRS-score < or = 16) had
      significantly higher serum IL 8 levels (p = 0.027) and increased radioactivity
      uptake ratio in the pons (P = 0.036) than the patients with more severe
      depressive symptoms (i.e. HDRS-score > 16). With regard to regional cerebral
      blood flow, significant correlations were detected between RSP and morning
      stiffness (r = 0.70, p < 0.01) and sleep disturbance (r = -0.53, p < 0.05), and
      between gyrus rectalis and FIQ score. There were significant correlations between
      LCN and IL-2 (P = 0.025), between RSP and morning stiffness (P = 0.006), sleep
      disturbance (P = 0.021) according to multiple regression analysis test.
      CONCLUSION: This study shows a significant increase in rCBF of caudate nuclei, a
      reduction in the pons, some cortical regions activity and a increase in IL 8,
      IL2r levels of young female patients with FM. These findings are more prominent
      in patients with low HDRS scores.

PMID- 12508766
TI  - Impaired glutathione reductase activity and levels of collagenase and elastase in
      synovial fluid in rheumatoid arthritis.
AB  - OBJECTIVE: To test the activity of elastase, collagenase and glutathione
      reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA)
      and in patients with osteoarthritis (OA); to correlate the elastase and
      collagenase activity with the glutathione reductase activity, which is important
      for the inactivation of oxygen free radicals. METHODS: 24 patients affected by
      osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the
      study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl
      alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly
      specific for elastase, and insensitive to the other serine proteases, such as
      cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as
      the substrate. Glutathione reductase activity was measured following the
      oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the
      presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase,
      collagenase and glutathione reductase were statistically higher in patients with
      RA than in patients with OA. Moreover, in the SF of patients with RA we found
      positive correlation between enzyme activity levels. CONCLUSION: These results
      confirm a high activity of collagenase and elastase in the SF of patients with
      RA, which is about 30 times higher than that found in the SF of patients with OA.
      These data underline the synergic action of these enzymes in the pathogenesis of
      joint damage. RA patients also exhibit higher levels of glutathione reductase,
      which is important for the detoxification pathway of oxygen free radicals.
      However, compared with findings for collagenase and elastase, the increase in
      glutathione reductase is only three times higher than level found in the SF of OA
      patients. The limited increase in glutathione reductase activity during the
      inflammatory process might lead to an insufficient protective effect at the joint
      level in rheumatoid arthritis.

PMID- 12508767
TI  - A one year followup of chronic arthritis following rubella and hepatitis B
      vaccination based upon analysis of the Vaccine Adverse Events Reporting System
      (VAERS) database.
AB  - OBJECTIVES: This analysis examined the incidence rate of chronic arthritis
      adverse reactions reported following adult rubella and hepatitis B vaccinations.
      In this analysis, etiologic mechanisms for chronic arthritis following adult
      rubella and hepatitis B vaccines were also explored. METHODS: The Vaccine Adverse
      Events Reporting System (VAERS) database was analyzed for the incidence rate of
      reported cases of chronic arthritis in comparison to Tetanus-diphtheria (Td) and
      tetanus toxoid adult vaccine control groups. RESULTS: Chronic arthritis adverse
      reactions following adult rubella vaccination were primarily reported in females
      (female/male ratio = 3.0), at about 45 years-old, and at a mean onset time of 10
      11 days following vaccination. Chronic arthritis adverse reactions following
      adult hepatitis B vaccination were also primarily reported in females(female/male
      ratio = 3.5), at about 33 years-old, and with a mean onset time of 16 days
      following vaccination. The incidence rates of chronic arthritis following adult
      rubella and adult hepatitis B vaccinations were statistically significantly
      increased, by chi 2 analysis, in comparison to the adult vaccine control groups.
      The attributable risk of chronic arthritis following adult rubella vaccine ranged
      from 32 to 53 and from 5.1 to 9.0 following adult hepatitis B vaccine in
      comparison to the adult vaccine control groups. CONCLUSION: This study revealed
      that adult rubella and adult hepatitis B vaccines were statistically associated
      with chronic arthritis which persisted for at least one year. The etiology for
      these adverse reactions may involve autoimmune mechanisms. Furthermore, potential
      biases in the reporting rates of adverse reactions to VAERS were not observed.

PMID- 12508768
TI  - Corticosteroid treatment induces chondrocyte apoptosis in an experimental
      arthritis model and in chondrocyte cultures.
AB  - OBJECT: In order to examine the mechanisms involved in steroid-induced
      arthropathy after intra-articular corticosteroid injection, a histological
      examination was performed in vivo using severe combined immunodeficiency (SCID)
      mice that were implanted with human articular cartilage into the back (SCID/hu
      model). In addition, the effect of corticosteroids on chondrocyte apoptosis was
      evaluated in vitro using cultured human chondrocytes. METHOD: Human articular
      cartilage was obtained during knee surgery and implanted subcutaneously into the
      backs of SCID mice. One month later, weekly injections of corticosteroid
      (hydrocortisone acatate: 1 mg/0.2 ml, triamcinolone acetonide: 0.2 mg/0.2 ml,
      dexamethasone acetate: 0.1 mg/0.2 ml) in the subcutaneous cavity around the
      grafted cartilage in SCID mice were initiated. After six weeks of treatment, the
      grafted cartilage pieces were removed from the SCID mice and examined
      histologically. Chondrocyte apoptosis after corticosteroid treatment was also
      investigated using cultured human chondrocytes. RESULT: In the corticosteroid
      treated, grafted articular cartilage, apoptotic chondrocytes were apparent in the
      superficial and middle layers of cartilage. But a reduced intensity of Safranin O
      staining was not remarkable. In the cultured chondrocytes, apoptotic changes were
      also observed after corticosteroid treatment. CONCLUSION: Corticosteroid
      treatment induces chondrocyte apoptosis and it may be important to understand the
      steroid-induced arthropathy.

PMID- 12508769
TI  - Antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis after
      immunisation with bacterial proteins.
AB  - OBJECTIVE: There is circumstantial evidence for a role for infections in the
      development of the small vessel vasculitides associated with antineutrophil
      cytoplasmic antibodies (ANCA). The aim of this study was to determine whether the
      immunisation of rats with bacterial proteins could result in circulating ANCA, T
      cells with specificity for ANCA antigens, and a systemic vasculitis. METHODS:
      Adult male Wistar rats were immunised with pasteurised sonicated S. aureus (n =
      7), E. coli (n = 8), purified protein derivative (PPD, n = 5), myeloperoxidase
      (MPO, n = 5) or phosphate-buffered saline (PBS, n = 5), in complete and in
      incomplete Freund's adjuvant. ANCA were assayed by indirect immunofluorescent
      (IIF) examination of normal rat neutrophils, and in ELISAs using human proteinase
      3 (PR3), MPO and bactericidal/permeability-inreasing protein (BPI). The T cell
      response to PR3, MPO and BPI was assessed by a whole blood T cell proliferative
      assay in vitro, and by a delayed type hypersensitivity (DTH) response in vivo.
      Kidney and bowel were examined histologically for evidence of vasculitis and
      colitis. RESULTS: One rat from each group immunised with S. aureus or E. coli
      developed pauciimmune segmental glomerular sclerosis. The rat immunised with E.
      coli had additionally an arteritis affecting renal interlobular and gut vessels.
      This rat had circulating C-ANCA, that produced granular cytoplasmic neutrophil
      fluorescence with central accentuation, but the target antigen could not be
      determined in ELISAs using human PR3, MPO or BPI. In animals immunised with S.
      aureus or E. coli, there was no significant T cell proliferative or DTH response
      specific for human PR3, MPO or BPI. CONCLUSION: The development of ANCA and
      vasculitis in a rat immunised with bacterial proteins indicates that the
      relationship between infections and ANCA should be investigated further.

PMID- 12508770
TI  - Expression of TNF-related apoptosis inducing ligand (TRAIL) on infiltrating cells
      and of TRAIL receptors on salivary glands in patients with Sjogren's syndrome.
AB  - BACKGROUND: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL)
      induces apoptosis of tumor cells but not normal cells; its role in normal non
      transformed tissues is unknown. OBJECTIVE: To evaluate the role of apoptosis
      mediated by TRAIL and TRAIL-receptor (TRAIL-R) system in lymphocytic sialadenitis
      in patients with Sjogren's syndrome. METHODS: The expression of TRAIL and TRAIL
      R1, 2, 3 and 4 in lymphocytic sialadenitis was examined by immunoperoxidase
      staining in patients with Sjogren's syndrome and in normal subjects. To elucidate
      the mechanism of de novo expression of TRAIL-R1 antigen, we quantitatively
      investigated its induction by cytokines in human salivary duct cell line (HSG) by
      cell enzyme-linked immunosorbent assay. In human salivary duct cells stimulated
      by cytokines, we investigated the induction of apoptotic cell death by
      recombinant TRAIL protein. RESULTS: In patients with massive mononuclear cell
      infiltration, some infiltrating cells showed TRAIL. In patients with severe
      lymphocytic sialadenitis, TRAIL-R1, TRAIL-R2, or both were strongly expressed on
      the ductal epithelial cells. Neither TRAIL-R3 nor R4 were observed on ductal
      epithelium. In contrast, TRAIL-R1 and R2 were not found in the minor salivary
      glands of normal subjects or patients with mild lymphocytic sialadenitis.
      Unstimulated HSG cells did not express TRAIL-R1. Interferon-gamma (IFN-gamma)
      consistently upregulated levels of TRAIL-R1. In contrast, tumor necrosis factor
      alpha (TNF-alpha), interleukin 1-beta (IL-1 beta), IL-2, and IL-4 had no effect
      on TRAIL-R1 levels. HSG cells expressing TRAIL-R1 in response to IFN-gamma were
      susceptible to apoptosis by recombinant TRAIL protein. CONCLUSION: Our findings
      suggest that TRAIL and TRAIL-R system may play a role in the pathogenesis of
      lymphocytic sialadenitis in patients with Sjogren's syndrome.

PMID- 12508771
TI  - VEGF release is associated with reduced oxygen tensions in experimental
      inflammatory arthritis.
AB  - OBJECTIVE: The contribution of local VEGF production and subsequent angiogenesis
      within the synovial membrane to the propagation of arthritis is unclear. The
      relationship between synovial oxygenation and blood flow in the development of
      arthritic disease is unknown. We have therefore measured oxygen levels and
      perfusion rates in the synovial space in a murine model of arthritis. METHODS:
      Arthritis was induced in DBA/1 mice by immunisation with type II collagen. Oxygen
      and perfusion levels were measured polarographically using silver needle
      microelectrodes within the knee joints prior to and 10 days after the onset of
      arthritis. In addition, synovial cells were isolated from knee joints of naive,
      pre-arthritic and arthritic mice. RESULTS: Onset of arthritis was associated with
      a marked reduction in synovial oxygen tensions (pO2). The perfusion rates in
      naive and arthritic animals were not significantly different: in naive mice, the
      rate was 0.58 +/- 0.11 ml/min/g and in arthritic joints, 0.64 +/- 0.17 ml/min/g.
      Furthermore, synovial cells isolated from the knee joints of naive animals did
      not express mRNA for VEGF, but significant levels were detected in cells from non
      arthritic mice immunised with collagen. The onset of arthritis was associated
      with expression of VEGF mRNA and protein, and correlated negatively with pO2
      levels. CONCLUSION: These data demonstrate that decreases in intra-articular pO2
      occur in established arthritic conditions and may be the stimulus for local VEGF
      production. However, perfusion was not increased in arthritic animals and
      vascular density was unaltered, suggesting that the neovascularisation associated
      with inflammatory arthritis, is insufficient to restore oxygen homeostasis in the
      joint.

PMID- 12508772
TI  - Hyperprolactinaemia in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To verify the presence of hyper-PRL in SLE patients, its association
      with high disease activity, specific organ involvement or presence of anti-ds-DNA
      antibodies. METHODS: The group under study consisted of 80 patients with systemic
      lupus erythematosus (SLE), 28 patients with rheumatoid arthritis (RA) and 27
      healthy controls. PRL serum levels were assayed using standard commercial kits
      (Immunotech Prague) with the radioimmunometric method for testing three samples
      of each of the subjects. The samples were taken in the morning hours (9-11 a.m.)
      of absolute rest 30 minutes after the introduction of the cannula at 30-minute
      intervals. RESULTS: A significantly higher rate of elevated PRL levels was found
      in SLE patients (40.0%) compared with the healthy controls (14.8%, p < 0.017). No
      proof was found of association with the presence of anti-ds-DNA or with specific
      organ involvement. Similarly, elevated PRL levels were found in RA patients
      (39.3%). The PRL elevation tended to decline from the 1st to the 3rd sample in
      the group of patients with SLE and RA but not in healthy controls. CONCLUSION: As
      follows from our measurements of prolactin serum values in SLE patients they are
      varriable by definition. According to our opinion further investigations are
      needed.

PMID- 12508773
TI  - Interleukin-10 expression: is there a neglected contribution of CD8+ T cells in
      rheumatoid arthritis joints?
AB  - OBJECTIVE: To search for RA specific processes among T cell accumulation, T cell
      activation, or cytokine expression in CD4+ and CD8+ synovial fluid (SF) T cells.
      METHODS: Flow cytometry of CD4+, CD8+, CD45RA+, CD45RO+, CD69 double or triple
      stained peripheral blood (PB) and SF T cells. IL-2, IL-10, and IFN-gamma
      expression was determined in PMA + ionomycin stimulated T cells on the single
      cell level. Concentrations of secreted IL-2, IL-4, IL-10, and IFN-gamma were
      quantified in the sera and synovial fluids by enzyme linked immunosorbent assay
      (ELISA). RESULTS: A preferential recruitment of CD45RO+ memory T cells was found
      for CD4+ helper T cells, and in similar also for CD8+ suppressor T cells. An
      elevated CD69 expression was detected in memory, but also in CD45RA+ naive CD4+
      and CD8+ SF T cells, whilst IL-2 expression was only demonstrable in a minor
      proportion of T cells populations. Preferential recruitment of memory T cells,
      but incomplete activation of naive and memory, CD4+ and CD8+ T cells were in
      similar found in RA and control patients. In RA but not in the control patients,
      a relevant proportion of CD4+ and CD8+ PB and SF T cells expressed IL-10 and IFN
      gamma. High concentrations of IL-10, that were correlated with the amounts of
      secreted TNF-alpha, were only detected in RA joints. CONCLUSION: Memory and naive
      T cell state of CD4+ and CD8+ T cell accumulates in the joints, and early T cell
      activation occur in similar patterns in RA and control patients. High IL-10 SF
      concentrations in contrast, and elevated percentages of IFN-gamma and IL-10
      expressing CD4+ and CD8+ T cells in the PB and SF were characteristic for RA.
      Here, CD8+ T cells may contribute to high IL-10 concentrations in RA joints.

PMID- 12508774
TI  - Association of CTLA-4 with systemic sclerosis in Japanese patients.
AB  - OBJECTIVE: The contribution of CTLA-4 alleles to the pathogenesis of systemic
      sclerosis (SSc) was studied in Japanese patients. METHODS: CTLA-4 typing in 2
      dimorphic sites, +49 A/G and -308 C/T, was carried out in 62 SSc patients and 107
      normal subjects by the PCR-RFLP (restriction fragment length polymorphism)
      method. HLA-DRB1*15 and *08 genotyping were carried out by the PCR-SSCP (simple
      stranded DNA conformation polymorphism) method. RESULTS: In SSc the frequency of
      the +49A allele increased slightly (40.3%), but was not significant. In SSc with
      diffuse scleroderma and SSc with anti-topoisomerase I antibody, the +49A also
      increased (43.8%, and 48.0%, respectively) but again was not significant. A
      significant increase in the +49A was not observed in SSc with HLA-DRB1*1502 or
      ORB1*0802. In contrast, the +49A had significantly increased in SSc with the anti
      RNP antibody [52.9%, p = 0.0337, Odds ratio (OR) = 2.27 (95% confidential
      interval (CI) = 1.09-4.71)]. HLA-DRB1*1502 and *0802 had no influence on the
      association of anti-RNP antibody with the +49A. The +49AA genotype increased
      significantly in SSc without lung fibrosis [31.8%, p = 0.0456, OR = 3.37 (CI =
      1.16-9.87)], especially in limited SSc without lung fibrosis [33.3%, p = 0.0319,
      OR = 3.62 (CI = 1.16-11.29)]. The dimorphism at -308 did not associate with SSc.
      CONCLUSION: In Japanese scleroderma, the +49A allele of CTLA-4 increased in the
      presence of SSc with the anti-RNP antibody.

PMID- 12508775
TI  - TNF +489 polymorphism does not contribute to susceptibility to rheumatoid
      arthritis.
AB  - OBJECTIVES: To determine if a tumour necrosis factor (TNF +489) polymorphism is
      associated with susceptibility to rheumatoid arthritis (RA). METHODS: Two
      European populations were studied: 217 controls and 238 patients from the north
      of England and 145 controls and 179 patients from Spain. HLA-DRB1 and TNF +489
      markers were typed using polymerase chain reaction based methods. RESULTS: Strong
      associations were demonstrated with shared epitope (SE) encoding HLA-DRB1 alleles
      in the English (OR = 2.9 [2.2-3.9]) and Spanish (OR = 2.3 [1.6-3.3]) populations,
      however no association was found with TNF +489 alleles. Furthermore carriage of
      TNF +489A was not associated with the presence of radiological erosions,
      rheumatoid nodules or rheumatoid factor. CONCLUSION: The role of the TNF locus in
      the genetic background of RA is unclear, however, our data does not support the
      previous reported association of the TNF +489A allele with RA susceptibility or
      severity.

PMID- 12508776
TI  - A cluster of inflammatory rheumatic diseases in a moisture-damaged office.
AB  - OBJECTIVE: To describe a cluster of inflammatory rheumatic diseases in an office
      workplace that suggests the presence of an environmental trigger. METHODS: There
      had been an indoor air problem in the workplace since the early 1990s. Large
      areas of the outer walls of the building were found to be moisture-damaged and
      contaminated by microbial growth. Case histories of the personnel were studied,
      and their working areas were related to the areas with highest microbial
      contamination. The incidence of inflammatory rheumatic diseases was compared with
      the statistics of the same geographic area. RESULTS: Ten patients with
      inflammatory rheumatic diseases (3 rheumatoid arthritis, 4 ankylosing
      spondylitis, 2 Sjogren's syndrome, and one of psoriatic arthritis) entitled to
      specially reimbursed medication were diagnosed in 1987-2000 (seven cases in 1995
      1998). The incidence density ratio computed for the period 1987-2000 was 6.8 (95%
      confidence interval 3.6-13.0) for all office personnel and 13.2 (6.0-29.0) for
      those working close to the wall sustaining the worst damage. CONCLUSION: The
      accumulation of chronic inflammatory rheumatic diseases in a single workplace
      suggests that some environmental exposure in this damp office had triggered the
      diseases.

PMID- 12508777
TI  - Low values of creatine kinase in systemic lupus erythematosus. Clinical
      significance in 300 patients.
AB  - OBJECTIVE: To study creatine kinase (CK) activity in a large series of patients
      with systemic lupus erythematosus (SLE) and identify the clinical and
      immunological features related to reduced levels. METHODS: In a cross-sectional
      study, serum CK activity was measured in 300 consecutive patients with SLE (271
      females and 29 males, with a mean age of 36 years). All patients fulfilled the
      1982 revised criteria of the American College of Rheumatology. RESULTS: Low serum
      CK levels (< 33 IU/L) were detected in 118 (39%) of SLE patients. When compared
      to SLE patients with normal serum CK levels, those with SLE and low serum CK
      levels had a higher frequency of fever (53% vs. 34%, p = 0.017), renal
      involvement (43% vs. 27%, p = 0.004), and hemolytic anemia (13% vs. 6%, p =
      0.037). In addition, SLE patients with low CK values also presented lower values
      of hemoglobin, total proteins, albumin, cholesterol and triglycerides, higher
      values of ESR and low C3 (44% vs. 27%, p = 0.004), C4 (57% vs. 37%, p = 0.001)
      and CH50 levels (60% vs. 41%, p = 0.02). We analysed in 69 patients the
      correlation between CK and 24-hour proteinuria values, and found that those with
      a 24-hour proteinuria > 1500 mg/day showed lower CK values than those with
      proteinuria < 1500 (31.95 vs 63.84 IU/L, p = 0.046). CONCLUSION: We observed that
      serum CK levels were reduced in 39% of SLE patients. Reduced serum CK activity
      was significantly related to some clinical (fever, nephropathy), hematological
      (high ESR, hemolytic anemia) and immunological (hypocomplementemia) features,
      which relate to disease activity. This suggest that reduced CK activity might be
      inversely correlated to inflammatory activity in SLE.

PMID- 12508778
TI  - FC gamma RIIa polymorphism in patients with rheumatoid arthritis.
AB  - OBJECTIVE: Polymorphism of phagocyte IgG receptor Fc gamma RIIa may modulate
      immune complex mediated inflammation, particularly when immune complex contain
      IgG2. METHODS: Fc gamma RIIa genotyping in 82 patients with rheumatoid arthritis
      (RA) and 148 healthy subjects was performed using the polymerase chain reaction
      technique with allele specific primers. RESULTS: No significant relation between
      Fc gamma RIIa genotypes and susceptibility to RA was observed, but extraarticular
      complications with high frequency were revealed in patients with R/R131 genotype.
      CONCLUSION: The results suggest that the Fc gamma RIIa polymorphism is not a risk
      factor for RA.

PMID- 12508779
TI  - Cutaneous vasculitis and reactive arthritis following respiratory infection due
      to Chlamydia pneumoniae: report of a case.
AB  - Unlike Chlamydia trachomatis and C. psittaci, the association of C. pneumoniae
      infection with immunological complications, such as reactive arthritis (ReA) or
      erythema nodosum (EN) has been rarely reported. Here we present the case history
      of a patient with C. pneumoniae community acquired pneumonia (CAP) who
      subsequently developed a ReA and a cutaneous vasculitis. A 45-year-old HLA B27
      negative male developed an asymmetric and additive arthritis and a cutaneous
      leukocytoclastic vasculitis with IgM and complement papillary deposition along
      hypodermic vessel walls about three weeks after the onset of respiratory
      symptoms. The diagnosis of chronic Chlamydia pneumoniae infection was based on
      serology and PCR. Cultural and serological investigations for other infectious
      agents commonly involved in ReA were negative. This is the first report on the
      occurrence of two immune-based complications, associated to Chlamydia pneumoniae
      infection. Therefore, since this infection is very common in our population,
      although often asymptomatic, should be systematically considered as a common
      causative agent of ReA and of vasculitis.

PMID- 12508780
TI  - Lymphoepithelioma-like carcinoma of the parotid gland in a patient with
      rheumatoid arthritis.
AB  - Lymphoepithelioma-like carcinoma (LELC) is an Epstein-Barr virus (EBV) related
      malignancy. It is not a common condition and is usually found in the head and
      neck region. We describe the development of LELC involving the parotid gland in a
      patient with rheumatoid arthritis (RA) who had been receiving long-term
      azathioprine. A brief review is also made on the clinical presentation and
      histological features of LELC and the association of RA with EBV related
      diseases. The latter may be attributed to an increase in risk of malignancy
      associated with RA or as a result of the long-term immunosuppressive used.

PMID- 12508781
TI  - Kelley-Seegmiller syndrome in a patient with complete hypoxanthine-guanine
      phosphoribosyltransferase deficiency.
AB  - Different degrees of hypoxanthine guanine phosphoribosyltransferase (HPRT)
      deficiency are associated with hyperuricemia, uric acid nephrolithiasis and
      severe gout. Up to 25-30% of HPRT deficient patients, indicated as neurological
      variants or HPRT-related hyperuricemia with neurological dysfunction (HRND), may
      develop neurological manifestation, from mild to severe; the most serious ones
      manifesting in the devastating Lesch-Nyhan syndrome, characterized by
      choreoathetosis or self-mutilation. Here we present a 30 years old male patient
      suffering from gout and mild psycho-motor impairment without Lesch Nyhan disease
      despite severe HPRT deficiency residual activity 0.02% with hypoxanthine, no
      activity at all with guanine as a substrate. The Curto's theory that neurologic
      impairment is dependent on VGPRT/VHPRT ratio is not confirmed by our
      observations. The finding of such a severe HPRT deficiency in a non-Lesch-Nyhan
      patient needs further investigation. G6PD deficiency was also referred together
      with beta-thalassemic trait. We have studied purine and pyridine nucleotide
      metabolism in the erythrocytes and discussed the literature. The bone marrow
      sample shows a megaloblastyc aspect.

PMID- 12508782
TI  - Diagnosis and assessment of systemic vasculitis.
AB  - The diagnosis of systemic vasculitis requires clinical evidence with appropriate
      symptoms and physical signs, supported by histological or radiological
      confirmation. Earlier recognition of these diseases has been facilitated by a
      greater awareness of their incidence, and also by the more widespread
      introduction of the anti-neutrophil cytoplasmic antibody (ANCA) test. Early
      diagnosis provides a greater potential for effective intervention in the course
      of disease and this may limit subsequent damage. However, an early diagnosis
      poses the more difficult challenge in the classification of the vasculitides,
      since traditional classification systems have depended on the presence of well
      established manifestations of the disease. The accurate assessment of disease
      activity and damage in vasculitis has become necessary as a result of significant
      improvements in survival with the use of chemotherapy. The disease course however
      is frequently characterised by relapse as well as the scars of irreversible organ
      damage from disease and drug toxicity. Clinical methods of assessment are simple
      to apply, reliable and often more effective than any current laboratory test in
      evaluating the effects of therapy and determining changes in therapy. The
      increasing use of surrogate clinical measures of disease should provide a greater
      opportunity to establish the effectiveness of existing and novel therapies in the
      management of these complex diseases.

PMID- 12508783
TI  - Levels of soluble CD27 in sera and synovial fluid and its expression on memory T
      cells in patients with juvenile idiopathic arthritides.
AB  - OBJECTIVE: CD27 is a member of tumour necrosis factor receptor family. Its
      expression is predominantly confined to mature lymphocytes and is strongly
      enhanced after cell activation. Shedding of the CD27 from the surface of
      activated cells is related to their effector phase. The aim of the present study
      was to evaluate the levels of soluble CD27 in sera and synovial fluids, together
      with its expression on circulating and synovial fluid (SF) memory T cells, in
      children with JIA. METHODS: Sera from 40 patients with active JIA were studied
      for soluble CD27. Paired SF samples were available in 20 patients. Sera from 12
      age-matched patients affected with various acute infectious diseases and 12 age
      matched healthy subjects were used as controls. In 8 JIA patients freshly
      isolated circulating and SF lymphocytes were stained for CD27 in CD4+CD45 RO+ T
      cell subpopulation and analyzed by cytometry. RESULTS: Soluble CD27 serum levels
      were significantly higher in patients with polyarticular JIA and acute systemic
      infectious diseases than in patients with active oligoarticular or healthy
      controls. Both polyarticular and oligoarticular JIA patients showed increased
      levels of soluble CD27 in SF when compared with paired serum samples (p = 0.01).
      In all the patients tested a significant enrichment of CD27- T cells was seen in
      the SF (median 39.5%, range 18-56%) when compared to paired CD4+CD45RO+
      peripheral lymphocytes (median 19.5%, range 5-43%; p = 0.01). CONCLUSIONS: A
      clear enrichment of CD4+ memory SF T cells with a CD27-phenotype is observed when
      compared to correspondent circulating T lymphocytes. This issue is conceivably
      related to re-activation and recruitment of memory T cells to the site of
      inflammation, and to the subsequent expansion of a subpopulation of "effector"
      memory T cells.

PMID- 12508784
TI  - Good results from combining etanercept to prevailing DMARD therapy in refractory
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: To assess the effect of etanercept added to prevailing drug therapy in
      patients with juvenile idiopathic arthritis (JIA) whose disease was refractory to
      conventional disease-modifying antirheumatic drug (DMARD) treatment, including
      combinations of different DMARDs. METHODS: Data on 31 JIA patients with a disease
      resistant to conventional DMARD treatment were retrospectively collected from
      medical records and assessed for a one-year period after the introduction of
      etanercept or to the time of cessation of the drug due to a lack of efficacy or
      side effects. Efficacy was assessed based on the normal laboratory indexes of
      inflammation and changes in the following parametres: number of DMARDs used and
      intraarticular (i.a.) glucocorticoid injections. The numbers of inpatient days
      needed were also recorded. RESULTS: Etanercept was well tolerated. Only two
      patients stopped discontinued the treatment because of allergic rash, after 3
      weeks of treatment in one case and after 4 months in another. In two cases the
      treatment was discontinued because of a lack of efficacy. During the treatment,
      there was a significant decrease in the number of DMARDs used and the i.a.
      glucocorticoid injections needed as well as in the dose of per oral
      glucocorticoids. The laboratory parameters also improved. In addition, there was
      a significant decrease in the number of inpatient days per 3-month period before
      and during the etanercept treatment. CONCLUSION: The addition of etanercept to
      conventional DMARD therapy in children with the most severe cases of JIA leads to
      an excellent clinical response during the first 12 months. The tolerability of
      the drug is good in combination therapy with various DMARDs.

PMID- 12508785
TI  - Two injections of interferon-alpha could trigger the development of rheumatoid
      arthritis.

PMID- 12508786
TI  - No association of interleukin-4 gene polymorphisms in Chinese patients with
      rheumatoid arthritis in Taiwan.

PMID- 12508787
TI  - Melatonin in rheumatoid arthritis: a disease-promoting and modulating hormone?

PMID- 12508788
TI  - A selective COX-2 inhibitor, meloxicam, as a treatment option in patients with
      juvenile idiopathic arthritis and gastrointestinal side effects from naproxen.

PMID- 12508789
TI  - Localization, structure and atomar composition of calcifications in temporal
      arteries.

PMID- 12508790
TI  - The central role of actinically degenerate elastic tissue.

PMID- 12508791
TI  - Contrast and velocity ultrasonic tomography of long bones.
AB  - Our objective is to derive quantitative sound speed images of cortical bone using
      ultrasonic transmission tomography. Cortical bone is a highly refracting medium,
      i.e., the sound velocity changes abruptly across the interface between soft
      tissue and bone. It results in a loss of data compared to classical tomography in
      soft tissues. In order to correct for degradation by refraction effects, the
      classical acquisition procedure of projection data is modified: the transducers
      are oriented according to Snell's law of refraction with the aim of optimizing
      the sound propagation as parallel longitudinal rays inside the bone. This
      strategy allows the subsequent application of straight-ray reconstruction by the
      backprojection technique, which is a classical procedure in x-ray tomography. The
      method is validated with Plexiglas solid cylinders and tubes immersed in water.
      Improved sound velocity images are then derived using conventional Radon
      transform of the experimental time-of-flight data. The method is then extended to
      in vitro human femur immersed in water. The geometry of the bone cross-section is
      reconstructed from measurements using ultrasonic reflection tomography. The
      result is then introduced in the calculation of the position and orientation of
      the transducers, which are associated with the parallel acoustical paths in bone
      in the transmission measurements. The procedure leads to significant restoration
      enhancement over the non corrected image. The mean value of the velocity of 3,200
      ms(-1) in the cortical shell is consistent with the values known from literature.
      These preliminary quantitative images using combined reflected and transmission
      ultrasound show promise for bone imaging.

PMID- 12508792
TI  - Single-tube nested PCR for detection of the sheep-associated agent of MCF.

PMID- 12508793
TI  - Extrapulmonary Legionella micdadei infection in a previously healthy child.
AB  - A previously healthy 9-year-old girl presented with a 1-week history of left neck
      mass and low grade fever. Surgical drainage specimens from the mass were
      bacterial culture-negative. Legionella micdadei infection was diagnosed by a two
      step PCR-nucleic acid sequencing method and supported by organism-specific
      serology. A backyard hot tub was suspected as the source of infection.

PMID- 12508794
TI  - Use of polymerase chain reaction for diagnosis of disseminated adenovirus
      infection.
AB  - We report a fatal case of disseminated adenovirus infection with fulminant
      hepatic failure in an 8-month-old child after peripheral blood stem cell
      transplantation. The virus was identified in blood, urine, respiratory aspirate
      and stool samples and was typed as adenovirus type 2 through PCR and sequencing
      of part of the hexon gene, with the use of degenerated consensus primers.

PMID- 12508795
TI  - Cardiac hydatid cyst and pulmonary hydatidosis in a child.
AB  - Hydatidosis in the lungs is unusual, and a cardiac localization occurs rarely. We
      report a child with cardiac hydatid cyst that developed during albendazole
      treatment for preceding multiple pulmonary hydatid lesions. The cardiac lesion
      was treated by surgical excision, and the pulmonary cysts improved with a
      combination of praziquantel and albendazole therapy.

PMID- 12508796
TI  - Radiocontrast nephropathy: managing the high-risk patient. Introduction.

PMID- 12508797
TI  - Which is the better method for assessing changes on Doppler  echocardiograms?

PMID- 12508798
TI  - Quetiapine treatment of adolescent and child tic disorders. Two case reports.

PMID- 12508799
TI  - Ebola-Poe: a modern-day parallel of the red death?

PMID- 12508800
TI  - Bibliography. Current world literature. Myeloid biology and disease.

PMID- 12508801
TI  - Bibliography. Current world literature. Asthma.

PMID- 12508802
TI  - [Without cell death there is no life].

PMID- 12508803
TI  - Office of Inspector General (OIG) issues draft compliance program for
      pharmaceutical manufacturers.

PMID- 12508804
TI  - Still rewarding after 24 years.

PMID- 12508805
TI  - Annual spring meeting of the Austrian Society of Hematology and Oncology. 23-25
      April 1998, Baden, Vienna. Abstracts.

PMID- 12508806
TI  - Coronary artery disease treatment in the catheterization laboratory: the promise
      of an evolving new pharmaco-mechanical approach. Introduction.

PMID- 12508808
TI  - Abstracts of the 4th Middle European Congress of Internal Medicine. July 1-3,
      1999.

PMID- 12508807
TI  - 1999 Spring Meeting of the Austrian Society of Hematology and Oncology.
      Abstracts.

PMID- 12508809
TI  - Meat sanitary control in Spain during the XIXth century.

PMID- 12508810
TI  - [Enteroviruses--again and again the cause of serous meningitis].

PMID- 12508811
TI  - Response from the Behavior Change Consortium Representatives and Translation Work
      Group: the issue is one of impact, not of world view or preferred approach.

PMID- 12508812
TI  - Balancing smokers, nonsmokers and health concerns.
AB  - Delaware and California have banned all public smoking. Other states are looking
      at requiring separate, well-vented rooms. The problem is no one knows how much
      ventilation is enough.

PMID- 12508813
TI  - Hurdles of health care reform.
AB  - The obstacles are enormous, and so are the stakes. But there are some new ideas
      for reining in health care costs and keeping Americans healthy.

PMID- 12508814
TI  - [The development of veterinary medicine in Finland].

PMID- 12508815
TI  - Veterinary research in Finland.

PMID- 12508816
TI  - Gut 2002, Annual Scientific Meeting. 27-30 June 2002. Abstracts.

PMID- 12508817
TI  - Proceedings of the 1st National Congress of the Italian Society of Herbal
      Sciences. Fiuggi, Italy, 8-10 October 1999.

PMID- 12508818
TI  - European research on functional effects of dietary antioxidant: benefits and
      risks. 25-28 September 2002, Cambridge, United Kingdom. Abstracts.

PMID- 12508819
TI  - Obstructive sleep apnoea.

PMID- 12508820
TI  - Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over
      the-counter human use; final monograph for combination drug products. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule in the form of a
      final monograph that establishes conditions under which over-the-counter (OTC)
      cold, cough, allergy, bronchodilator, and antiasthmatic (cough-cold) combination
      drug products are generally recognized as safe and effective and not misbranded
      as part of its ongoing review of OTC drug products. FDA is issuing this final
      rule after considering public comments on the agency's proposed regulation
      (tentative final monograph) and new data and information on OTC cough- cold
      combination drug products that have come to the agency's attention.

PMID- 12508821
TI  - The Norwegian Society for the history of veterinary medicine.

PMID- 12508822
TI  - A short survey of the history of large animal surgery in Norway.

PMID- 12508823
TI  - The history of the eradication of rabies in most European countries.

PMID- 12508824
TI  - [International influence of the Pasteur Institute: centennial of the first
      Turkish institute of veterinary bacteriology].

PMID- 12508825
TI  - 100 years of veterinary microbiological institutes in Turkey.

PMID- 12508826
TI  - Grief consolation in eulogy rhetoric: an integrative framework.
AB  - In an ever more deadly and uncertain world, rhetoric honoring the deceased is
      still examined as though that was its primary, if not only, function. Some
      critics of eulogia also identify the consolation of survivors but rarely define
      it precisely or analyze its rhetorical execution. This article introduces a
      framework for the critical analysis and production of eulogia that draws from
      comforting mechanisms recognized in the interpersonal communication, social
      psychology, and grief therapy literatures. Self-disclosure, problem-focused
      coping, positive reappraisal, and the affirmation and continuation of
      relationships with the deceased are shown to inform criticism of five
      contemporary eulogies. Challenges inherent in the invention and appreciation of
      eulogy rhetoric are thus illuminated and addressed.

PMID- 12508827
TI  - Bereaved parents' outcomes 4 to 60 months after their children's deaths by
      accident, suicide, or homicide: a comparative study demonstrating differences.
AB  - In this article, the authors revisit a controversial issue in the bereavement
      field: Does one violent cause of death of a child influence parents' outcomes
      more than another? To address this question, we observed 173 parents
      prospectively 4, 12, 24, and 60 months after their children's deaths by accident,
      suicide, or homicide. Quantitative and qualitative research methods were used to
      examine the influence of three types of a child's violent death and time since
      death upon 4 parent outcomes (mental distress, post-traumatic stress disorder
      [PTSD], acceptance of the child's death, and marital satisfaction). The results
      showed a significant interaction for the bereavement Group x Time effect for
      acceptance of death, a significant main effect for time for all four outcomes,
      and a significant main effect for group (homicide) for PTSD. Nearly 70% of the
      parents reported that it took either 3 or 4 years to put their children's death
      into perspective and continue with their own lives; however the child's cause of
      death did not significantly influence parents' sense of timing in this regard.
      Clinical and research implications of the findings are discussed.

PMID- 12508828
TI  - Perceived income inequality and suicide rates in Central/Eastern European
      countries and Western countries, 1990-1993.
AB  - Sociological studies on cross-national male and female suicide rates have found
      numerous factors related to variation in suicide rates. The present study focuses
      on how perceived differences in income inequality impact suicide rates in 12
      different countries, unlike most prior studies on income inequality and suicide
      that use measures of actual income inequality. Using G. Jasso's (1999) index on
      perceived income inequality, the author found that perceived income inequality is
      related more strongly and more consistently to male suicide rates than female
      suicide rates. Relative to other variables used in this analysis,perceived income
      inequality also accounts for most of the difference in the gender gap of male
      versus female suicide rates.

PMID- 12508829
TI  - The Collett-Lester Fear of Death Scale: a correction.
AB  - A revision of the Collett-Lester Fear of Death Scale is presented, eliminating a
      deviant item that reduced the reliability of the scale. Using a sample of 191
      undergraduates, four 7-item subscales were derived with adequate reliabilities
      and factorial congruence for 2 of the subscales (Fear of Death of Self and Fear
      of Dying of Self).

PMID- 12508830
TI  - Nurse investigator. Interview by Alison Moore.

PMID- 12508831
TI  - [Surgery in Eastern Europe II. Proceedings of the European Society of Surgery,
      Budapest].

PMID- 12508832
TI  - [Surgical mesh implants in surgery of inguinal hernia].

PMID- 12508833
TI  - Neuroreceptor imaging in psychiatric disorders.
AB  - Molecular imaging, the study of receptors, transporters and enzymes, as well as
      other cellular processes, has grown in recent years to be one of the most active
      neuroimaging areas. The application of single photon emission tomography (SPECT)
      and positron emission tomography (PET) techniques to the study of psychiatric
      illness has lead to increased understanding of disease processes as well as
      validated, in vivo, theories of illness etiology. Within the field of psychiatry
      these techniques have been applied most widely to the study of schizophrenia.
      Studies within schizophrenia are largely limited to either the dopamine or
      serotonin system. This is due in large part to the availability of suitable
      radiotracers as well as the current theories on the etiology of the illness. Two
      basic study designs are used when studying schizophrenia using molecular imaging
      and make up the majority of studies reviewed in this manuscript. The first type,
      termed "clinical studies," compares the findings from PET and SPECT studies in
      those with schizophrenia to normal controls in an attempt to understand the
      pathophysiology of the illness. The second study design, termed "occupancy
      studies," uses these techniques to enhance the understanding of the mechanism of
      action of the medications used in treating this illness. This review will focus
      on the findings of molecular imaging studies in schizophrenia, focusing, for the
      most part, on the serotonin and dopamine systems. Emphasis will be placed on how
      these findings and techniques are currently being used to inform the development
      of novel treatments for schizophrenia.

PMID- 12508834
TI  - Anti-tachycardia therapy can improve altered cardiac adrenergic function in
      tachycardia-induced cardiomyopathy.
AB  - We investigated whether anti-tachycardia therapy might improve the altered
      cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy
      (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients
      with heart failure, consisting of 8 patients with TC (43.6 +/- 10.0 yrs) and 15
      with DCM (45.3 +/- 8.2 yrs). TC was determined as impairment of left ventricular
      function secondary to chronic or very frequent arrhythmia during more than 10% of
      the day. All patients were receiving anti-tachycardia treatment. Cardiac 123I
      MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and
      after treatment. LVEF was also assessed. In the baseline study, H/M and LVEF
      showed no difference between TC and DCM (2.21 +/- 0.44 vs. 2.10 +/- 0.42, 35.3 +/
      13.1 vs. 36.0 +/- 10.9%, respectively). After treatment, the degree of change in
      H/M and LVEF differed significantly (0.41 +/- 0.34 vs. 0.08 +/- 0.20, 20.5 +/-
      14.4 vs. -2.1 +/- 9.6%, p < 0.01). In TC, heart failure improved after a shorter
      duration of treatment (p < 0.05). In conclusion, anti-tachycardia therapy can
      improve altered cardiac adrenergic function and systolic function in patients
      with TC over a shorter period than in those with DCM.

PMID- 12508835
TI  - The retention indices of 201Tl-SPECT in brain tumors.
AB  - OBJECTIVE: The aim of this study was to assess the utility of 201Tl SPECT in the
      differential diagnosis of intracranial tumors and to determine the relationship
      between 201Tl uptake and histological types. METHODS: Thirty-eight patients (19
      males and 19 females) with thirty-eight brain tumors were evaluated with 201Tl
      SPECT. The early and delayed 201Tl uptake ratio was calculated, and the retention
      index (RI) was applied as follows; RI = delayed uptake ratio/early uptake ratio.
      RESULTS: The RI of malignant tumors was higher (0.72 +/- 0.18) than that of
      benign tumors (0.50 +/- 0.16) and the difference was statistically significant (p
      = 0.00045). The difference between high-grade glioma (0.80 +/- 0.15) and
      metastatic tumors (0.64 +/- 0.19) was statistically significant (p = 0.039).
      CONCLUSION: 201Tl-SPECT may add useful biochemical information and could
      differentiate malignant brain tumors from benign lesions, but the RI of
      metastatic tumors varied depending on the organs with the primary lesion and
      histological types.

PMID- 12508836
TI  - The role of Tc-99m polyclonal human immunoglobulin G scintigraphy in Graves'
      ophthalmopathy.
AB  - OBJECTIVE: The aim of this study was to clarify whether Tc-99m HIG (Polyclonal
      Human Immunoglobulin G) can image and determine the severity of orbital
      involvement in patients with Graves' ophthalmopathy. MATERIALS AND METHODS:
      Twenty-six patients between 19 and 56 years old with Graves' ophthalmopathy were
      examined. All patients received approximately 370 MBq Tc-99m HIG by i.v.
      injection. Planar and SPECT examination were performed 4 hours after the
      injection. Visual and semiquantitative evaluations were performed for both orbits
      by two independent observers, RESULTS: Clinically active ophthalmopathy patients
      had noticeably increased orbital accumulation of Tc-99m HIG. In patients with
      inactive disease, and 14 of 19 had no uptake, whereas 5 patients had orbital
      radioactivity accumulation. The duration of Graves' ophthalmopathy did not
      correlate with the presence of active ophthalmopathy and Tc-99m HIG grade. There
      was no correlation between clinical classification and clinical activity (r =
      278). There was a good correlation between clinical activity and the
      radioactivity grade with r = 0.666 (p = 0.01). The clinical classification
      closely correlated with Tc-99m HIG grade (r = 0.423, p = 0.05). CONCLUSION: Tc
      99m HIG scan can clearly identified clinically active patients, and subclinicial
      inflammation can be shown by this scintigraphic evaluation. The current
      preliminary results suggested that Tc-99m HIG SPECT might be useful for the
      assessment of disease activity in Graves' ophthalmopathy.

PMID- 12508837
TI  - Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after
      quinolinic acid lesion: comparison with the dopamine receptor imaging.
AB  - We proposed [11C]KF18446 as a selective radioligand for mapping the adenosine A2A
      receptors being highly enriched in the striatum by positron emission tomography
      (PET). In the present study, we investigated whether [11C]KF18446 PET can detect
      the change in the striatal adenosine A2A receptors in the rat after unilateral
      injection of an excitotoxin quinolinic acid into the striatum, a Huntington's
      disease model, to demonstrate the usefulness of [11C]KF18446. The extent of the
      striatal lesion was identified based on MRI, to which the PET was co-registered.
      The binding potential of [11C]KF18446 significantly decreased in the quinolinic
      acid-lesioned striatum. The decrease was comparable to the decrease in the
      potential of [11C]raclopride binding to dopamine D2 receptors in the lesioned
      striatum, but seemed to be larger than the decrease in the potential of [11C]SCH
      23390 binding to dopamine D1 receptors. Ex vivo and in vitro autoradiography
      validated the PET signals. We concluded that [11C]KF18446 PET can detect change
      in the adenosine A2A receptors in the rat model, and will provide a new
      diagnostic tool for characterizing post-synaptic striatopallidal neurons in the
      stratum.

PMID- 12508838
TI  - Technetium-99m-DTPA aerosol scintigraphy in amiodarone induced pulmonary toxicity
      in comparison with Ga-67 scintigraphy.
AB  - Amiodarone hydrochloride, which is used in life-threatening cardiac
      tachyarrhythmia, has been known to cause amiodarone induced pulmonary toxicity
      (AIPT) as a complication. In this study we aimed to investigate the clinical
      value of technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol lung
      scintigraphy in patients with AIPT in comparison with gallium-67 (Ga-67) scan.
      The study group included 26 cases, 7 patients with diagnosis of AIPT (Group A), 8
      patients receiving amiodarone therapy but without AIPT (Group B) and 11 healthy
      subjects as a control group (Group C). All patients underwent Ga-67 and Tc-99m
      DTPA aerosol scintigraphy in addition to various laboratory tests, Ga-67
      scintigraphy was positive in 4 of 7 AIPT patients but quite normal in Group B. A
      positive correlation was found (r = 0.52, p < 0.05) between kep values determined
      by Tc-99m-DTPA aerosol scintigraphy and the cumulative dose of amiodarone. The
      mean kep values were 2.04% +/- 0.85%/min, 1.30% +/- 0.42%/min and 0.86% +/-
      0.19%/min for groups A, B and C, respectively. The mean clearance rate of group A
      was significantly faster than that of normals (p < 0.0005) and group B (p =
      0.028). In addition, there was a significant difference between groups B and C (p
      = 0.015). In conclusion, Ga-67 lung scintigraphy is a useful method for the
      detection of AIPT but Tc-99m-DTPA aerosol scintigraphy offers better results than
      Ga-67 scintigraphy. Early changes in Tc-99m-DTPA clearance may be observed in
      patients receiving amiodarone. The kep value in patients with AIPT is noticeably
      increased with respect to the control group. With its favorable physical
      properties, low cost, lower radiation burden and its ability to be used as an
      objective measure for the pulmonary clearance rate, Tc-99m-DTPA aerosol
      scintigraphy appears to be promising in patients receiving amiodarone therapy.

PMID- 12508839
TI  - Subhyoid ectopic thyroid with mediolateral location in a developmentally retarded
      child with hypothyroidism in an iodine deficiency region.
AB  - The authors present a case of subhyoid ectopic thyroid with mediolateral location
      diagnosed by technetium-99m pertechnetate scan. The ectopia was associated with
      hypothyroidism and developmental retardation.

PMID- 12508840
TI  - Lung uptake on a bone scan: a case of pulmonary Waldenstrom's macroglobulinemia.
AB  - Pulmonary involvement secondary to Waldenstrom's macroglobulinemia (WMG) is
      described in a 40-year-old male by incidental findings on a bone scan. He was
      examined for right leg pain, and bone scan revealed unexpected pulmonary uptake
      of Tc-99m MDP. CT scan of the thorax revealed pleural effusion and slightly
      disseminated micronoduler density increase in the right lung and parenchymal
      infiltration in the left lung. Transdermal lung biopsy demonstrated diffuse
      infiltration of lymphoplasmocytoids. Reporting the presence of pulmonary
      involvement is important because it may prevent morbidity from pulmonary
      dysfunction.

PMID- 12508841
TI  - Clinical diagnosis: Intrahepatic arteriovenous fistula associated with hereditary
      hemorrhagic telangiectasia.

PMID- 12508842
TI  - Whole-body PET with FDG is useful for following up an ovarian cancer patient with
      only rising CA-125 levels within the normal range.
AB  - In April 2000, a 54-year-old woman underwent surgery for ovarian serous cell
      carcinoma (stage IIb). After initial treatment, the patient underwent a physical
      examination, ultrasound examination and measurement of serum CA-125 levels every
      month. Although neither diagnostic imaging (ultrasound and computed tomography)
      nor physical examination showed any evidence of recurrence, the CA-125 level rose
      slowly and continuously within the normal range. In March 2001, an increased
      accumulation of 18F-fluorodeoxyglucose (FDG) in the pelvic cavity was seen on a
      positron emission tomography (PET) scan obtained 2 weeks before a relapse of a
      malignant lesion was diagnosed by gadolinium-enhanced MRI (Gd-MRI). It is
      reasonable to suppose that FDG-PET is clinically useful for detecting an early,
      small region of relapsed ovarian cancer. Moreover, FDG-PET may be helpful for
      determining whether a patient who has a continuous rising CA-125 level within the
      normal range should be treated in the absence of relapse regions detected by
      conventional methods.

PMID- 12508843
TI  - Extraosseous accumulation of 99mTc phosphonate complexes in primary brain tumor
      evaluated with SPECT.
AB  - Although extraosseous accumulations of 99mTc phosphate complexes are phenomena
      which can often be seen, no case showing extraosseous accumulation to brain tumor
      on SPECT has been reported. We report here two cases of primary brain tumor
      showing extraosseous accumulation of 99mTc phosphate in bone SPECT. 201Tl SPECT
      also showed increased 201Tl uptake by the tumor. Comparing bone SPECT with 201Tl
      SPECT, the regions of abnormality of both SPECTs were very similar in the case of
      glioblastoma, but in the case of malignant lymphoma the region showing intense
      uptake of 99mTc-MDP was smaller than that on 201Tl SPECT. It was revealed that
      bone SPECT is more useful in the assessment of extraosseous accumulation to a
      primary brain tumor than conventional bone scintigraphy.

PMID- 12508844
TI  - Reduced Tc-99m DMSA uptake in a patient with renal tubular acidosis: effect of
      acid-base imbalance.
AB  - Tc-99m dimercaptosuccinic acid (DMSA) is used as a renal cortical imaging agent
      to detect parenchymal abnormalities especially in children. Kidney uptake of DMSA
      provides an index for evaluation of a functional tubular mass, which depends on
      the renal blood flow and proximal tubular cell membrane transport function. We
      here report a boy with renal tubular acidosis, which has noticeably reduced
      uptake on his Tc-99m DMSA scintigraphy, despite a totally normal Tc-99m MAG-3
      study. The case reported here clearly demonstrates a situation in which renal
      uptake of DMSA may be dissociated from a functional renal mass and the importance
      of acid-base balance which alters Tc-99m DMSA uptake.

PMID- 12508845
TI  - Comparison of [18F]FDG-PET and L-3[123I]-iodo-alpha-methyl tyrosine (I-123 IMT)
      SPECT in primary lung cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate L-3[123I]-iodo-alpha-methyl
      tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung
      cancer. METHODS: Whole body PET (measured transmission corrected emission scans)
      was performed 45 minutes after i.v. injection of 222-370 MBq (6-10 mCi) 18F-FDG
      on a Siemens PET scanner (ECAT EXACT 47) including 5-6 bed positions. 123I-IMT
      SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head
      camera (Picker Prism 2000) and commercially available reconstruction algorithms.
      Ten patients (6 male and 4 female) with suspected lung cancer were investigated.
      The results were compared to histological findings after surgery or bronchoscopic
      biopsies and CT. RESULTS: 123I-IMT-SPECT and FDG-PET were able to detect all 9
      cases of lung cancer (1-8 cm in diameter). One case was true negative. Both
      imaging methods were true positive with respect to mediastinal lymph node
      metastases in one patient. The tumor/background ratio was higher with PET (8.20
      vs. 2.84). CONCLUSION: Despite the limited number of patients it may be concluded
      that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer.
      Nevertheless, FDG-PET, if available, seems to be better suited because of the
      higher tumor/background ratio and better resolution.

PMID- 12508846
TI  - Enhancement of the relative uptake of 18F-FDG in mouse fibrosarcoma by rolipram.
AB  - The effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the
      uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumor tissue was examined in mice
      transplanted with NFSa fibrosarcoma. The uptake indexes of 18F-FDG in the heart,
      skeletal muscle and brain remarkably decreased after treatment with 3 mg/kg of
      rolipram (heart: 13%, skeletal muscle: 14%, brain: 31%), but fibrosarcoma tissue
      showed only a 50% reduction in the uptake index of 18F-FDG. The tumor/muscle
      ratio of radioactivity 30 min after 18F-FDG injection was consequently enhanced
      from 1.9 to 6.5 by rolipram. This indicates the possible use of rolipram to
      enhance the sensitivity of tumor detection, as well as characterization of tumors
      in 18F-FDG PET.

PMID- 12508847
TI  - Prediction of therapy response to interferon-alpha in chronic viral hepatitis-B
      by liver and hepatobiliary scintigraphy.
AB  - Interferon (IFN) provides effective treatment in some patients with chronic
      hepatitis. The clarification of factors predictive of therapy response would be
      helpful in identifying patients who would benefit from treatment. In this study,
      we evaluated the potential utility of Tc-99m sulfur colloid liver/spleen and Tc
      99m-disofenin hepatobiliary scintigraphy to predict therapy response to IFN in
      patientswith chronic active hepatitis. The study group consisted of ten patients
      with chronic viral hepatitis B who were treated with 4.5 units of interferon
      alpha for 12 months. Prior to the start of the therapy, sulfur colloid
      scintigraphy was obtained by which the liver/spleen ratios were derived.
      Hepatobiliary scintigraphy was performed on a separate day and time-activity
      curves were generated from regions of interest drawn over the liver, heart and
      gall-bladder. The index of blood and liver clearance time was calculated.
      Histological grading and laboratory values were obtained for clinical
      correlation. Responders (n = 6) to IFN were defined as those who improved
      clinically with normalized transaminase levels and had HBeAg seroconversion. On
      SC scintigraphy, the liver/spleen ratio of non-responders was significantly lower
      than responders (median values: 0.69 vs. 1.16, p = 0.01) but on hepatobiliary
      scintigraphy no statistically significant parameters were found to predict
      response to interferon therapy.

PMID- 12508848
TI  - Rathayibacter caricis sp. nov. and Rathayibacter festucae sp. nov., isolated from
      the phyllosphere of Carex sp. and the leaf gall induced by the nematode Anguina
      graminis on Festuca rubra L., respectively.
AB  - Two novel species, Rathayibacter caricis sp. nov. (type strain VKM Ac-1799T = UCM
      Ac-618T) and Rathayibacter festucae sp. nov. (type strain VKM Ac-1390T UCM Ac
      619T), are proposed for two coryneform actinomycetes found in the phyllosphere of
      Carex sp. and in the leaf gall induced by the plant-parasitic nematode Anguina
      graminis on Festuca rubra L., respectively. The strains of the novel species are
      typical of the genus Rathayibacter in their chemotaxonomic characteristics and
      fall into the Rathayibacter 16S rDNA phylogenetic cluster. They belong to two
      separate genomic species and differ markedly from current validly described
      species of Rathayibacter at the phenotypic level. The most striking feature
      differentiating Rathayibacter caricis sp. nov. from other species of the genus is
      the presence of fucose in its cell wall and Rathayibacter festucae sp. nov. can
      be easily recognized among other yellow-pigmented rathayibacters because of its
      rose-orange-coloured colonies.

PMID- 12508849
TI  - Propionimicrobium gen. nov., a new genus to accommodate Propionibacterium
      lymphophilum (Torrey 1916) Johnson and Cummins 1972, 1057AL as Propionimicrobium
      lymphophilum comb. nov.
AB  - Based upon significant differences in chemotaxonomic properties, i.e., amino acid
      composition of peptidoglycan, fatty acids and base composition of DNA, and
      supported by the phylogenetic position of the 165 rDNA sequence the species
      Propionibacterium lymphophilum was reclassified as Propionimicrobium lymphophilum
      comb. nov.

PMID- 12508850
TI  - Desulfitobacterium metallireducens sp. nov., an anaerobic bacterium that couples
      growth to the reduction of metals and humic acids as well as chlorinated
      compounds.
AB  - Strain 853-15A(T) was enriched and isolated from uranium-contaminated aquifer
      sediment by its ability to grow under anaerobic conditions via the oxidation of
      lactate coupled to the reduction of anthraquinone-2,6-disulfonate (AQDS) to
      anthrahydroquinone-2,6-disulfonate (AHQDS). Lactate was oxidized incompletely to
      acetate and carbon dioxide according to the reaction CH3CHOHCOO(-)+ 2AQDS+H2O -->
      CH3COO(-)+ 2AHQDS+CO2. Additional electron donors utilized included formate,
      ethanol, butanol, butyrate, malate and pyruvate. Lactate also supported growth
      with Fe(III) citrate, Mn(IV) oxide, humic substances, elemental sulfur, 3-chloro
      4-hydroxyphenylacetate, trichloroethylene or tetrachloroethylene serving as the
      electron acceptor. Growth was not observed with sulfate, sulfite, nitrate or
      fumarate as the terminal electron acceptor. The temperature optimum for growth
      was 30 degrees C, but growth was also observed at 20 and 37 degrees C. The pH
      optimum was approximately 7.0. The 16S rDNA sequence of strain 853-15A(T)
      suggested that it was most closely related to Desulfitobacterium dehalogenans and
      closely related to Desulfitobacterium chlororespirans and Desulfitobacterium
      frappieri. The phylogenetic and physiological properties exhibited by strain 853
      15A(T) (= ATCC BAA-636(T)) place it within the genus Desulfitobacterium as the
      type strain of a novel species, Desulfitobacterium metallireducens sp. nov.

PMID- 12508851
TI  - Stenotrophomonas rhizophila sp. nov., a novel plant-associated bacterium with
      antifungal properties.
AB  - A polyphasic taxonomic study was performed on 16 Stenotrophomonas strains from
      environmental and clinical sources. A group of three plant-associated isolates
      were shown to be phenotypically different from the other strains. This group
      formed a separate physiological cluster (B1) with 42% heterogeneity to the other
      isolates. The defining characteristics of the new species were as follows: growth
      at 4 degrees C and the absence of growth at 40 degrees C; the utilization of
      xylose as a carbon source; lower osmolytic tolerance (< 4.5% NaCl, w/v), although
      the isolates can produce trehalose and glucosylglycerol as osmoprotective
      substances; the absence of lipase and beta-glucosidase production; and antifungal
      activity against plant-pathogenic fungi. The whole-cell fatty acid profile of
      this group was different and characterized by the main fatty acids iso-C15:0 and
      anteiso-C15:0. Numerical analysis of the fatty acid profiles of the strains
      examined supports the differentiation of the physiological B1 group. By 16S rDNA
      analysis, three clusters were distinguished. The three strains of the B1 group
      formed a separate environmental cluster (E1). They showed a mean similarity of
      99.5% within the cluster, and differed from strains of a second environmental
      cluster (E2) by 2.2% and from the clinical cluster (C) by about 3.0%. DNA-DNA
      hybridization data supported the taxonomic differentiation. All results led to
      the proposal of a new species, Stenotrophomonas rhizophila sp. nov., with strain
      e-p10(T) (= DSM 14405(T) = ATCC BAA-473(T)) as the type strain.

PMID- 12508852
TI  - Unification of Bifidobacterium infantis and Bifidobacterium suis as
      Bifidobacterium longum.
AB  - The relationships between Bifidobacterium infantis, Bifidobacterium longum and
      Bifidobacterium suis were examined by means of carbohydrate fermentation, DNA-DNA
      hybridization, ribotyping and random amplified polymorphic DNA-PCR (RAPD-PCR).
      The levels of DNA-DNA hybridization among the strains of B. infantis, B. longum
      and B. suis used in this study were 67-81% under optimal conditions (42 degrees
      C) and 63-85% under stringent conditions (52 degrees C). Although the strains
      showed varied carbohydrate-fermentation patterns, the three species were divided
      into three types, namely the infantis type, the longum type and the suis type, by
      ribotyping and RAPD-PCR. On the basis of these results, strains of B. infantis,
      B. longum and B. suis were recognized as distinct groups within a single species.
      It is concluded that B. infantis and B. suis should be unified as B. longum, the
      latter species being divided into three biotypes, the infantis type, the longum
      type and the suis type, by molecular methods.

PMID- 12508853
TI  - Farnesyl diphosphate synthase gene of three phototrophic bacteria and its use as
      a phylogenetic marker.
AB  - Farnesyl diphosphate (FPP) synthase is essential not only for phototrophic
      bacteria in carotenoid biosynthesis, but also for non-phototrophic bacteria in
      the biosynthesis of physiologically important compounds. The gene encoding FPP
      synthase was assessed as a molecular marker to investigate the intermingled
      relationship between the phototropic and non-phototropic bacteria in the alpha
      Proteobacteria based on 16S rRNA analysis. The FPP synthase amino acid sequences
      from three phototropic bacteria, Rhodobacter sphaeroides ATCC 11167(T),
      Rhodobacter capsulatus ATCC 11166(T) and Rhodovulum sulfidophilum W4(T), were
      determined and used in conjunction with sequences of other representative members
      of the alpha-, gamma- and epsilon-Proteobacteria and the low-G+C Gram-positive
      bacteria for phylogenetic analyses by the neighbour-joining and maximum
      likelihood methods. The overall topology of the FPP synthase gene tree is
      consistent with that of the 16S rRNA tree, producing a distinct cluster of the
      three phototropic bacteria. A minor discordance between the two trees was
      observed in the cluster of the non-phototrophic Bradyrhizobiumjaponicum USDA 110
      and Mesorhizobium loti MAFF 303099; the FPP synthase genes of these two rhizobial
      species are highly homologous as compared with their respective 16S rRNA. The
      results suggest that the FPP synthase and 16S rRNA genes have the same
      evolutionary pattern, evolving vertically from each common ancestral gene; the
      FPP synthase gene, therefore, could possibly be used for further study on the
      molecular systematics of photosynthetic bacteria.

PMID- 12508854
TI  - Carboxydocella thermautotrophica gen. nov., sp. nov., a novel anaerobic, CO
      utilizing thermophile from a Kamchatkan hot spring.
AB  - A novel anaerobic, thermophilic, CO-utilizing bacterium, strain 41(T), was
      isolated from a terrestrial hot vent on the Kamchatka Peninsula. Strain 41(T) was
      found to be a Gram-positive bacterium, its cells being short, straight, motile
      rods. Chains of three to five cells were often observed. The isolate grew only
      chemolithoautotrophically on CO, producing equimolar quantities of H2 and CO2
      (according to the equation CO+H2O --> CO2+H2). Growth was observed in the
      temperature range 40-68 degrees C, with an optimum at 58 degrees C, and in the pH
      range 6.5-7.6, with an optimum at pH 7.0. The generation time under optimal
      conditions for chemolithotrophic growth was 1.1 h. The DNA G+C content was 46 +/-
      1 mol%. Growth was completely inhibited by penicillin, ampicillin, streptomycin,
      kanamycin and neomycin. On the basis of the phenotypic and phylogenetic features,
      it is proposed that this isolate represents a new genus and species,
      Carboxydocella thermautotrophica gen. nov., sp. nov. (type strain 41(T) = DSM
      12356(T) = VKM B-2282(T)).

PMID- 12508855
TI  - DNA-DNA reassociation and phenotypic data indicate synonymy between Aeromonas
      enteropelogenes Schubert et al. 1990 and Aeromonas trota Carnahan et al. 1991.
AB  - Mainly on the basis of phylogenetic and genotypic evidence, it has been suggested
      previously that the species Aeromonas enteropelogenes Schubert et al. 1990 is
      identical to the species Aeromonas trota Carnahan et al. 1991. Probably because
      the description of A. enteropelogenes preceded the proposal of A. trota by only a
      few months, DNA-DNA hybridizations were never performed between representative
      strains of these two taxa. In the present study, new DNA-DNA hybridizations
      between the type strain of A. enteropelogenes, LMG 12646(T) (= DSM 6394(T)), and
      reference strains of A. trota, including its type strain LMG 12223(T)(= ATCC
      49657(T)), showed a genomic relatedness of 81-99%. In addition, phenotypic
      characterization revealed that the two type strains exhibited identical API 20E
      and API 50CHE biochemical profiles and were both susceptible to ampicillin and
      carbenicillin. Collectively, our new DNA reassociation and phenotypic data
      confirm previous taxonomic data that indicate that the taxa A. enteropelogenes
      and A. trota are synonymous members of the same Aeromonas species. Although the
      species name A. enteropelogenes has nomenclatural priority, the authors would
      like to discourage the use of this name because the name A. trota has been cited
      much more frequently. The preferential use of A. trota in future publications may
      be the best option to avoid ambiguity in the description of ampicillinsusceptible
      aeromonads and to secure nomenclatural continuity in Aeromonas literature.

PMID- 12508856
TI  - Pseudomonas costantinii sp. nov., another causal agent of brown blotch disease,
      isolated from cultivated mushroom sporophores in Finland.
AB  - Pathogenic bacteria are frequently associated with mushroom sporophores
      exhibiting brown blotch disease symptoms. These bacteria belong mainly to
      Pseudomonas tolaasii or occasionally to 'Pseudomonas reactans'. Although a group
      of isolates originating from some Finnish mushroom farms satisfied the two
      characteristic criteria for diagnosis of infection with P. tolaasii (i.e.
      yielding a typical brown blotch symptom on Agaricus bisporus sporophores and
      producing a typical white line in agar when streaked towards the 'P. reactans'
      LMG 5329 inducing strain), results based on numerical taxonomy, siderotyping, DNA
      DNA hybridizations and 16S rDNA phylogenetic analyses supported the view that
      these isolates constituted a novel species within the genus Pseudomonas,
      Pseudomonas costantinii. The type strain is PS 3a(T) (= CFBP 5705(T) = HAMBI
      2444(T)).

PMID- 12508857
TI  - Bacillus luciferensis sp. nov., from volcanic soil on Candlemas Island, South
      Sandwich archipelago.
AB  - Aerobic, endospore-forming bacteria were found in soil taken from an active
      fumarole on Lucifer Hill, Candlemas Island, South Sandwich archipelago. Amplified
      rDNA restriction analysis, SDS-PAGE, repetitive element primed-PCR (rep-PCR) and
      routine phenotypic tests suggested that six of the isolates represent a novel
      taxon, and 16S rDNA sequence comparisons support the proposal of a novel species,
      Bacillus luciferensis sp. nov., the type strain of which is strain LMG 18422(T)
      (= CIP 107105(T)).

PMID- 12508858
TI  - Mycobacterium holsaticum sp. nov.
AB  - Strains of a novel species of the rapidly growing mycobacteria, Mycobacterium
      holsaticum sp. nov., were isolated from various clinical specimens. The isolates
      grew at 22-40 degrees C, were positive for nitrate and tellurite reduction, had
      phosphatase, urease, nicotinamidase and pyrazinamidase activities, were resistant
      to isoniazid and rifampin and were susceptible to streptomycin and ethambutol.
      Analyses of the 165 rRNA gene and a fragment of the heat-shock protein gene hsp65
      revealed unique nucleotide sequences. A phylogenetic analysis based on the
      comparison of the 16S rDNA sequence with that of other mycobacterial species
      allocated the strain to the rapidly growing mycobacteria. A conspicuous
      characteristic of the novel species is the similarity of the species-specific
      sequence of the 16S rRNA gene to the sequence of the Mycobacterium tuberculosis
      complex, resulting in a cross-reaction with the AccuProbe for the M. tuberculosis
      complex when performed with a 5 min selection step. The type strain of the novel
      species is strain 1406(T) ( = DSM 44478(T) = CCUG 46266(T)). Another strain of M.
      holsaticum sp. nov., strain 5050, which differed in the internal transcribed
      spacer sequence, was deposited as DSM 44479 ( = CCUG 46267).

PMID- 12508859
TI  - Classification of a polycyclic aromatic hydrocarbon-metabolizing bacterium,
      Mycobacterium sp. strain PYR-1, as Mycobacterium vanbaalenii sp. nov.
AB  - A polycyclic aromatic hydrocarbon (PAH)-utilizing Mycobacterium strain, PYR-1(T),
      was isolated from petroleum-contaminated estuarine sediments and has been shown
      by 16S rRNA gene sequencing to be closely related to Mycobacterium aurum ATCC
      23366(T) and Mycobacterium vaccae ATCC 15438(T). In this investigation, the 16S
      rDNA, fatty acid methyl esters, DNA-DNA hybridization, PFGE analysis of
      restriction-digested total genomic DNA and biochemical tests were used to
      determine the taxonomic relationship of strain PYR-1(T) to other closely related
      Mycobacterium species. The sequence of the 16S rRNA gene of strain PYR-1(T) was
      similar to that of Mycobacterium austroafricanum ATCC 33464(T), except for one
      gap at position 43. Fatty acid methyl ester analysis also showed similarity to M.
      austroafricanum ATCC 33464(T); however, the Euclidean distance was greater than
      4.0, indicating that these strains were not identical. Dot-blot DNA-DNA
      hybridization of strain PYR-1(T) with M. austroafricanum indicated less than 40%
      relatedness. When the total chromosomal DNA of M. aurum ATCC 23366(T), M.
      austroafricanum ATCC 33464(T) and strain PYR-1(T) was digested with restriction
      enzyme Xbal and analysed by PFGE, all three organisms gave different restriction
      patterns. Previous studies from our laboratory have shown that the reverse-phase
      HPLC elution profiles of mycolic acids of strain PYR-1(T) and M. austroafricanum
      ATCC 33464(T) have different patterns. Based on phylogenetic analysis using 165
      rRNA gene sequences, fatty acid analysis, DNA-DNA hybridization and PFGE analysis
      and physiological and chemotaxonomic characteristics, it is concluded that strain
      PYR-1(T) (= DSM 7251(T) = NRRL B-24157(T)) represents a novel species of the
      genus Mycobacterium, for which the name Mycobacterium vanbaalenii sp. nov. is
      proposed.

PMID- 12508860
TI  - Phylogenetic analysis of the genus Pediococcus, including Pediococcus claussenii
      sp. nov., a novel lactic acid bacterium isolated from beer.
AB  - Pediococci are found in foods and on plants and as beer-spoilage agents. The goal
      of the present study was to use the DNA sequences of the first three variable
      regions of the 165 rRNA gene, the 16S-23S rRNA internally transcribed spacer
      region sequence and approximately a third of the 60 kDa heat-shock protein gene
      to elucidate phylogenetic groupings within the genus Pediococcus. Phylogenetic
      trees were created with sequence data from 31 Pediococcus and three Lactobacillus
      isolates. Complete 16S rRNA gene sequences from selected Pediococcus isolates
      were also examined. The results were interpreted in relation to the currently
      accepted Pediococcus species. We found that, where previously done, speciation of
      many Pediococcus isolates is inaccurate. Also, one grouping of seven isolates did
      not include any currently recognized Pediococcus species type isolate. Our
      phylogenetic analyses support the conclusion that these seven isolates, all of
      brewing spoilage origin, belong to a novel species, for which the name
      Pediococcus claussenii sp. nov. is proposed (type strain P06(T0 = ATCC BAA-344(T)
      = DSM 14800(T)). Phylogenetic analysis has therefore helped to resolve problems
      surrounding species identification of Pediococcus isolates.

PMID- 12508861
TI  - Streptomyces avermitilis sp. nov., nom. rev., a taxonomic home for the avermectin
      producing streptomycetes.
AB  - The taxonomic status of 'Streptomyces avermitilis' strain MA-4680 was established
      using a polyphasic approach. Strain MA-4680 formed a distinct phyletic line in
      the 16S rDNA streptomycete tree, and it was evident from the almost complete 16S
      rDNA sequence data that it was most closely related to Streptomyces cinnabarinus,
      Streptomyces griseochromogenes, Streptomyces resistomycificus and Streptomyces
      viridochromogenes. However, strain MA-4680 was readily distinguished from the
      type strains of these species by using a range of phenotypic properties, notably
      morphological and pigmentation features. The combined genotypic and phenotypic
      datasets indicate that the organism forms a recognizable centre of variation
      within the genus Streptomyces. It is proposed that 'Streptomyces avermitilis' be
      formally recognized as a species of Streptomyces. The type strain is MA-4680(T)
      (ATCC 31267(T) = NCIMB 12804(T0 = NRRL 8165(T)).

PMID- 12508862
TI  - Enterovibrio norvegicus gen. nov., sp. nov., isolated from the gut of turbot
      (Scophthalmus maximus) larvae: a new member of the family Vibrionaceae.
AB  - Twenty-two isolates originating from the gut of healthy cultured turbot larvae in
      Norway were investigated using a polyphasic approach. Amplified fragment length
      polymorphism fingerprinting analysis showed that the isolates have typical
      patterns and form two main groups. Phylogenetic analysis revealed that the
      isolates belong to the gamma-Proteobacteria, with Vibrio hollisae as their
      closest neighbour. DNA-DNA hybridization, chemotaxonomic and phenotypic analyses
      further proved that these isolates represent a tight novel taxon that differs
      from currently described species in the family Vibrionaceae. It is proposed that
      these novel isolates be accommodated in a new genus, Enterovibrio gen. nov., with
      Enterovibrio norvegicus sp. nov. as the type species. Isolates were motile by a
      polar flagellum, positive for oxidase, catalase, arginine dihydrolase and beta
      galactosidase, but negative for the Voges-Proskauer reaction. They produced
      indole, did not reduce nitrate and were resistant to the vibriostatic agent
      O/129. The DNA G+C content of E. norvegicus was 47.1-47.9 mol%. The type strain
      is E. norvegicus LMG 19839(T) (= CAIM 430(T)).

PMID- 12508863
TI  - Identification of the bacterial endosymbionts in leaf galls of Psychotria
      (Rubiaceae, angiosperms) and proposal of 'Candidatus Burkholderia kirkii' sp.
      nov.
AB  - This paper reports the identification of bacterial endosymbionts inhabiting the
      leaf galls of Psychotria kirkii. A phylogenetic approach was used to reveal the
      identity of these as yet uncultivable bacterial endophytes. Based on the analysis
      of 16S rDNA sequences, evolutionary trees were constructed that place the
      endosymbiont in the genus Burkholderia. Low levels of sequence identity and
      rather large evolutionary distances to the closest validly named relatives
      indicate that these symbiotic bacteria represent a novel species. Until
      cultivation is successful or until more phenotypic data become available the
      provisional name 'Candidatus Burkholderia kirkii' sp. nov. is proposed.

PMID- 12508864
TI  - Sphingopyxis witflariensis sp. nov., isolated from activated sludge.
AB  - Classification of strain W-50(T), which was isolated from a wastewater treatment
      plant, was investigated by a polyphasic approach. Cells of strain W-50(T) were
      Gram-negative, strictly aerobic, oxidase-positive and yellow-pigmented.
      Ubiquinone Q-10 was the main respiratory lipoquinone system and polar lipid
      fingerprints were characterized by the presence of a sphingoglycolipid,
      suggesting that strain W-50(T) belongs to the alpha-4 subclass of the
      Proteobacteria. Sequencing and comparative analyses of the 16S rRNA gene of
      strain W-50(T) supported its chemotaxonomic allocation as an alpha-4
      proteobacterium. The most closely related established taxa were species of the
      genus Sphingopyxis, including Sphingopyxis macrogoltabida (97.3% similarity) and
      Sphingopyxis terrae (96-4% similarity), and Sphingomonas taejonensis (97.3%).
      These findings were supported by both the polyamine content, which consisted
      mainly of spermidine [12.9 micromol (g dry wt)(-1)], and the presence of 2-OH
      14:0, 2-OH 15:0 and 2-OH 16:0 in the cellular fatty acid profile. DNA-DNA
      hybridization experiments resulted in similarity values of 31.9% between strain W
      50(T) and Sphingopyxis macrogoltabida IFO 15033(T), 44.9% between strain W-50(T)
      and Sphingopyxis terrae IFO 15098(T) and 31.0% between strain W-50(T) and
      Sphingomonas taejonensis KCTC 2884(T). Based upon results obtained by detailed
      physiological/biochemical testing and previously published molecular evidence,
      strain W-50(T) was clearly distinguishable from all other Sphingopyxis species.
      For these reasons, the creation of a novel species, Sphingopyxis witflariensis
      sp. nov., is proposed; strain W-50(T) (= DSM 14551(T) = CIP 107174(T)) is the
      type strain.

PMID- 12508865
TI  - Emended description of Rickettsia felis (Bouyer et al. 2001), a temperature
      dependent cultured bacterium.
AB  - On the basis of phenotypic data obtained on the strain Marseille-URRWFXCal2(T),
      isolated from the cat flea Ctenocephalides felis, the description of Rickettsia
      felis (Bouyer et al., 2001) is emended and Marseille-URRWFXCal2(T) is proposed as
      the type strain of the species. On the basis of polyphasic characterization,
      especially the inability to grow at temperatures higher than 32 degrees C on Vero
      cells that allow growth of other Rickettsia to at least 35 degrees C, it is
      confirmed that this agent, although different from other recognized rickettsial
      species, is genotypically indistinguishable from bacteria previously detected
      within cat fleas and provisionally named ELB. Comparison of the phenotypic
      characteristics previously described for R. felis and those observed for the
      isolate in this study indicated some differences, although concurrent analysis of
      the two was not possible as no extant isolates of the first isolate of R. felis
      exist.

PMID- 12508866
TI  - Lentibacillus salicampi gen. nov., sp. nov., a moderately halophilic bacterium
      isolated from a salt field in Korea.
AB  - A Gram-variable, aerobic, endospore-forming, rod-shaped bacterial strain, SF
      20(T), which was isolated from a salt field in Korea, was subjected to a
      polyphasic taxonomic study. Cells of this organism were motile by means of single
      flagella. Strain SF-20(T) grew optimally in the presence of 4-8% NaCl. The cell
      wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino
      acid. The predominant menaquinone is MK-7. Strain SF-20(T) has a cellular fatty
      acid profile containing major amounts of branched fatty acids. The major fatty
      acids are anteiso-C15:0 and iso-C16:0. The cellular phospholipids are
      phosphatidylglycerol and diphosphatidylglycerol. The G+C content of the DNA is 44
      mol%. Strain SF-20(T) is phylogenetically closely related to the genus Bacillus
      and some related genera and, particularly, formed a coherent cluster with the
      genera Salibacillus and Virgibacillus. The clustering fidelity between strain SF
      20(T) and the cluster comprising these two genera was supported by bootstrap
      analysis at a confidence level of 67.2%. Strain SF-20(T) exhibited levels of 16S
      rDNA similarity of 93.0-94.7% to the genus Salibacillus and 94.0-94.1% to the
      genus Virgibacillus. On the basis of phenotypic and phylogenetic data, strain SF
      20(T) should be classified in a novel genus and species, for which the name
      Lentibacillus salicampi gen. nov., sp. nov. is proposed. The type strain is
      strain SF-20(T) (= KCCM 41560(T) = JCM 11462(T)).

PMID- 12508867
TI  - Halomonas muralis sp. nov., isolated from microbial biofilms colonizing the walls
      and murals of the Saint-Catherine chapel (Castle Herberstein, Austria).
AB  - A group of seven halophilic strains (optimal growth at 2.5-10.0% NaCl) was
      isolated from samples of a wall and a mural painting, both heavily contaminated
      by microbial growth, inside the Saint-Catherine chapel of Castle Herberstein
      (Austria). The strains were subjected to a polyphasic taxonomic study that
      included DNA-DNA relatedness studies, DNA base-ratio determinations, 16S rDNA
      sequence analysis, rep-PCR genomic fingerprinting, fatty acid analysis and
      phenotypic and biochemical characterization. The data obtained indicate that the
      strains belong to the genus Halomonas and represent a novel species, for which
      the name Halomonas muralis sp. nov. is proposed. The type strain is strain LMG
      20969(T) ( = DSM 14789(T)).

PMID- 12508868
TI  - Rhodopseudomonas faecalis sp. nov., a phototrophic bacterium isolated from an
      anaerobic reactor that digests chicken faeces.
AB  - Five isolates of a previously undescribed species of purple non-sulfur
      phototrophic bacteria were characterized. They were Gram-negative, had mobile,
      budding vibrioid cells and contained lamellar intracytoplasmic membranes.
      Cultures produced red pigments in the light. Live cells of photosynthetic
      cultures exhibited absorption maxima at 382, 460-464, 494-496, 534-538, 596, 804
      806 and 870-874 nm, indicating the presence of bacteriochlorophyll a and
      carotenoids belonging to the spirilloxanthin series in cells. The new isolates
      grew anaerobically or microaerobically in the light, but not aerobically in the
      dark. Optimal growth occurred at 35-40 degrees C and at pH 6.5-8.5. Various
      organic compounds were used as photosynthetic electron donors and carbon sources.
      Sulfate was used as sulfur source for growth. Ubiquinone 10 was synthesized as
      the major quinone. A phylogenetic analysis based on 16S rRNA gene sequences
      revealed that strain gc(T), a representative of the new isolates, was closest to
      Rhodopseudomonas palustris, with a similarity of 97.5%. DNA-DNA hybridization
      further distinguished strain gc(T) from Rhodopseudomonas palustris at the species
      level. Therefore, the name Rhodopseudomonas faecalis sp. nov. was proposed for
      the new isolates. The type strain is gc(T) ( = AS1.2176(T) = JCM 11668(T)).

PMID- 12508869
TI  - Runella zeae sp. nov., a novel gram-negative bacterium from the stems of surface
      sterilized Zea mays.
AB  - A Gram-negative bacterium, designated NS12(T), was previously isolated from
      duplicate treatments of surface-sterilized Zea mays stems. The plants were grown
      in synthetic soil under greenhouse conditions and watered with fertilizer
      containing no nitrogen. Strain NS12(T) was not isolated from plants watered with
      the standard level or 20% (w/v) of the standard level of nitrogen. Cells were
      bent rods that formed chains of irregular shapes in R2A broth. Unlike its closest
      described relative Runella slithyformis, strain NS12(T) fermented glucose and
      sucrose. The G+C content was 49 mol%. Phylogenetic analysis of the 16S rRNA gene
      showed that the strain was a member of the domain Bacteria and is most closely
      related to R. slithyformis, a member of the Flexibacter group within the
      Cytophaga-Flexibacter-Bacteroides phylum. Phenotypic and genotypic analyses
      indicated that strain NS12(T) could not be assigned to any recognized species;
      therefore a new species designated Runella zeae sp. nov. is proposed, for which
      NS12(T) ( = ATCC BAA-293(T) = LMG 21438(T)) is the type strain.

PMID- 12508870
TI  - Pseudomonas salomonii sp. nov., pathogenic on garlic, and Pseudomonas
      palleroniana sp. nov., isolated from rice.
AB  - A total of 26 strains, including 15 strains isolated from garlic plants with the
      typical symptoms of 'Cafe au lait' disease and 11 strains isolated from diseased
      or healthy rice seeds and sheaths infested by Pseudomonas fuscovaginae, were
      compared with 70 type or reference strains of oxidase-positive pathogenic or non
      pathogenic fluorescent pseudomonads. The strains were characterized by using a
      polyphasic taxonomic approach. Numerical taxonomy of phenotypic characteristics
      showed that the garlic and rice strains were related to each other. However, they
      clustered into separate phenons, distinct from those of the other strains tested,
      and were different in several nutritional tests. On the basis of DNA-DNA
      hybridization, the garlic and rice strains constituted two distinct DNA
      hybridization groups, indicating that they belonged to separate species. The two
      groups of strains were also well differentiated by siderotyping. Garlic strains
      were pathogenic to garlic plants and either weakly pathogenic or non-pathogenic
      on rice; rice strains were either weakly pathogenic or non-pathogenic on rice and
      non-pathogenic on garlic. A phylogenetic analysis of 16S rRNA gene sequences
      confirmed that the two groups of strains belonged to the y-Proteobacteria and to
      the genus Pseudomonas. The names Pseudomonas salomonii sp. nov. and Pseudomonas
      palleroniana sp. nov. are respectively proposed for the garlic strains and the
      rice strains. The type strains are P. salomonii CFBP 2022(T) ( = ICMP 14252(T) =
      NCPPB 4277(T)) and P. palleroniana CFBP 4389(T) (= ICMP 14253(T) = NCPPB
      4278(T)).

PMID- 12508871
TI  - Investigation of the phylogenetic relationships within the genus Bartonella based
      on comparative sequence analysis of the rnpB gene, 16S rDNA and 23S rDNA.
AB  - A variety of genes and analytical methods have been applied to the study of
      phylogenetic relationships within the genus Bartonella, but so far the results
      have been inconsistent. While previous studies analysed single protein-encoding
      genes, we have analysed an alignment containing the sequences of three important
      phylogenetic markers, RNase P RNA, 16S rRNA and 23S rRNA, merged by catenation,
      to determine the phylogenetic relationships within the genus Bartonella. The
      dataset described here comprises 13 different Bartonella strains, including the
      seven strains that are known to be human pathogens. A variety of algorithms have
      been used to construct phylogenetic trees based on the combined alignment and,
      for comparison purposes, each individual gene. Trees generated from the catenated
      alignment are more consistent (independent of algorithm) and robust (higher
      bootstrap support). It is suggested that a phylogenetic analysis incorporating
      the RNase P RNA, 16S rRNA and 23S rRNA be used to study the phylogenetic
      relationships within the genus Bartonella.

PMID- 12508872
TI  - Sphingomonas melonis sp. nov., a novel pathogen that causes brown spots on yellow
      Spanish melon fruits.
AB  - A polyphasic taxonomic study was performed on the phytopathogenic bacterial
      strains DAPP-PG 224(T) and DAPP-PG 228, which cause brown spot on yellow Spanish
      melon (Cucumis melo var. inodorus) fruits. Based on the presence of glucuronosyl
      ceramide (SGL-1) in cellular lipids, the results of fatty acid analysis and 16S
      rDNA sequence comparison, the strains had been identified as belonging to the
      genus Sphingomonas and as phylogenetically related to Sphingomonas mali,
      Sphingomonas pruni and Sphingomonas asaccharolytica. The levels of 16S rDNA
      sequence similarity of these three species to strain DAPP-PG 224(T) were
      respectively 98.0, 98.0 and 97.4%. DNA-DNA hybridization experiments between
      strains pathogenic on melon fruit and S. mali, S. pruni and S. asaccharolytica
      revealed < or = 16% relatedness. Based on these results, the two isolates studied
      are regarded as independent from the type strains of the three species mentioned
      above. Sphingomonas strains from melon fruits are recognized as forming a
      genetically and phenotypically discrete species and to be differentiated by
      phenotypic characteristics from all 29 named species of the genus. Thus, the name
      Sphingomonas melonis sp. nov. is proposed for the isolates from diseased melon
      fruits. The type strain is DAPP-PG 224(T) (= LMG 19484(T) = DSM 14444(T)). The
      G+C content of DNA of the type strain is 65.0 mol%.

PMID- 12508873
TI  - 16S rDNA sequence analysis of environmental Bdellovibrio-and-like organisms
      (BALO) reveals extensive diversity.
AB  - Bdellovibrio-and-like organisms (BALO) are Gram-negative, predatory bacteria that
      inhabit terrestrial, freshwater and salt-water environments. Historically, these
      organisms have been classified together despite documented genetic differences
      between isolates. The genetic diversity of these microbes was assessed by
      sequencing the 16S rRNA gene. Primers that selectively amplify predator 16S rDNA,
      and not contaminating prey DNA, were utilized to study 17 freshwater and
      terrestrial and nine salt-water BALO isolates. When the 16S rDNA sequences were
      compared with representatives of other bacterial classes, 25 of the 26 BALO
      isolates clustered into two groups. One group, supported 100% by bootstrap
      analysis, included all of the Bdellovibrio bacteriovorus isolates. Each member of
      this group was isolated from either a freshwater or terrestrial source. The
      genetic distance between these isolates was less than 12%. The other group,
      supported 94% by bootstrap analysis, includes Bacteriovorax starrii,
      Bacteriovorax stolpii and the salt-water isolates. The salt-water isolates form a
      subgroup (83% by bootstrap) and differ within the subgroup by less than 110%.
      This observation implies that the salt-water isolates arose from Bacteriovorax
      progenitors. The difference between isolates in different clades is over 17%, a
      quantity similar to differences between bacterial species in different classes.
      However, both the Bdellovibrio and Bacteriovorax clades were closest to other
      representatives of the delta-Proteobacteria using maximum-likelihood. One
      freshwater isolate, James Island, was distinct from all other BALO (> 19%), but
      differed from Pseudomonas putida, a member of the gamma-Proteobacteria, by only
      3%. Thus, by 16S rDNA sequence analysis, the BALO appear to have multiple
      origins, contrary to the unified taxonomic grouping based on morphology and
      natural history. These observations are consistent with the need to review and
      revise the taxonomy of these organisms.

PMID- 12508874
TI  - Citricoccus muralis gen. nov., sp. nov., a novel actinobacterium isolated from a
      medieval wall painting.
AB  - A Gram-positive, aerobic, spherical actinobacterium, designated strain 4-0(T),
      was isolated from a medieval wall painting and characterized to determine its
      taxonomic position. The peptidoglycan of strain 4-0(T) was of type A4alpha, with
      lysine as the diagnostic cell wall diamino acid and an interpeptide bridge of Lys
      Gly-Glu. Its quinone system contained predominantly MK-9(H2) (64%) and its polar
      lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol, four unknown glycolipids, two unknown phospholipids and an
      unknown lipid. The fatty acid profile of strain 4-0(T) was represented by
      significant amounts of ai-C15:0 and moderate amounts of ai-C17:0, i-C16:0 and i
      C15:0 fatty acids. Spermidine was predominant in the polyamine pattern. The G+C
      content of the genomic DNA was 68 mol%. Comparative 16S rDNA sequence studies
      revealed the highest similarity values (95.4-96.1%) between strain 4-0(T) and
      species of the genus Micrococcus and certain species of the genus Arthrobacter,
      including Arthrobacter pascens DSM 20545(T), Arthrobacter ramosus DSM 20546(T),
      Arthrobacterprotophormiae DSM 20168(T), Arthrobacternicotianae DSM 20123(T) and
      Arthrobacter globiformis DSM 20124(T). Phylogenetic analyses demonstrated that
      strain 4-0(T) branches deeply on the Micrococcus lineage. Because it is almost
      equidistant phylogenetically from the genera Micrococcus and Arthrobacter and
      possesses significant differences in chemotaxonomic characteristics from members
      of these genera, it is suggested that strain 4-0(T) be classified as a novel
      species in a new genus; the name Citricoccus muralis gen. nov., sp. nov. is
      proposed. The type strain is strain 4-0(T) (= DSM 11442(T) CCM 4981(T)).

PMID- 12508875
TI  - Shewanella olleyana sp. nov., a marine species isolated from a temperate estuary
      which produces high levels of polyunsaturated fatty acids.
AB  - Two polyunsaturated fatty acid (PUFA) producing strains (ACEM 6 and ACEM 9(T))
      isolated from a temperate, humic-rich river estuary in Tasmania, Australia, were
      found to be members of the genus Shewanella. These strains were able to utilize
      humic compounds (tannic acid) and derivatives (2,6-anthraquinone disulfonate) as
      sole carbon sources and as electron acceptors for anaerobic respiration. The
      major fatty acids were typical of the genus Shewanella; however, PUFAs mostly
      made up of eicosapentaenoic acid were produced at high levels (10.2-23.6% of
      total fatty acids) and at relatively high incubation temperatures (10.2% at 24
      degrees C). Sequence analysis indicated that ACEM 6 and ACEM 9(T) had identical
      16S rDNA sequences and were most closely related to Shewanella japonica (sequence
      similarity 97.1%). DNA hybridization and phenotypic characteristics confirmed
      that the isolates constituted a novel species of the genus Shewanella, which is
      designated Shewanella olleyana sp. nov. (type strain ACEM 9(T) = ACAM 644(T) =
      LMG 21437(T)).

PMID- 12508876
TI  - Paenibacillus daejeonensis sp. nov., a novel alkaliphilic bacterium from soil.
AB  - The taxonomy of soil isolates AP-20(T) and AP-37 was examined. These alkaliphilic
      organisms grew over a wide pH range (pH 7.0-13.0). The growth rate was higher at
      pH 8.0-12.0 than at pH 7.0. The G+C composition of these strains averaged 53
      mol%. These strains contained MK-7 as the main respiratory quinone and meso
      diaminopimelic acid in the cell-wall peptidoglycan. The major cellular fatty acid
      of the isolates was 12-methyltetradecanoic acid. Levels of 16S rDNA similarity
      between strain AP-20(T), AP-37 and other Paenibacillus species were 94.2-90.2%.
      Phylogenetic analysis based on 16S rDNA sequence revealed that strains AP-20(T)
      and AP-37 formed an evolutionary lineage distinct from other Paenibacillus
      species. Based on the evaluation of morphological, physiological and
      chemotaxonomic characteristics, and on 16S rDNA sequence comparison, the new
      species Paenibacillus daejeonensis sp. nov. is proposed; the type strain is AP
      20(T) ( = KCTC 3745(T) = JCM 11236(T)).

PMID- 12508877
TI  - Pseudomonas extremorientalis sp. nov., isolated from a drinking water reservoir.
AB  - On the basis of phenotypic and genotypic characteristics and 16S rDNA sequence
      analysis, a novel species belonging to the genus Pseudomonas sensu stricto was
      identified. The saprophytic, fluorescent bacterium, designated KMM 3447(T), was
      isolated from a drinking water reservoir near Vladivostok City, Russia. The novel
      organism was a Gram-negative, aerobic, rod-shaped bacterium that produced a
      cyclic depsipeptide with surface-active properties. It degraded casein, but did
      not degrade gelatin, starch, agar or Tween 80. The bacterium was also haemolytic.
      Growth of the novel bacterium occurred between 4 and 35 degrees C. The
      predominant cellular fatty acids of the novel pseudomonad were C16:0, C16:1(n-7),
      C18:1(n-7) and C17.0 cyclo; branched fatty acids were only found in trace
      amounts. The G+C content of the novel bacterium was 61.0 mol%. 16S rDNA sequence
      analysis indicated that the novel bacterium had a clear affiliation with
      Pseudomonas fluorescens and species closely related to this recognized
      pseudomonad. DNA-DNA hybridization experiments showed that the novel bacterium
      bound at low levels (27-53%) with the DNA of the type strains of its nearest
      phylogenetic relatives, namely Pseudomonas tolaasii, Pseudomonas veronii,
      Pseudomonas orientalis and Pseudomonas rhodesiae, indicating that the novel
      bacterium represented a novel species within the genus Pseudomonas, for which the
      name Pseudomonas extremorientalis is proposed; the type strain is KMM 3447(T) (=
      LMG 19695(T)).

PMID- 12508878
TI  - Rhodococcus maanshanensis sp. nov., a novel actinomycete from soil.
AB  - A polyphasic study was undertaken to establish the taxonomic position of a soil
      isolate that had provisionally been assigned to the genus Rhodococcus. The
      organism showed a combination of phenotypic properties typical of rhodococci and
      formed a distinct phyletic line within the Rhodococcus erythropolis 165 rDNA
      subclade. The organism was readily distinguished from representatives of validly
      described species classified in this subclade on the basis of DNA-DNA relatedness
      and phenotypic data. Consequently, it is proposed that the organism be recognized
      as a novel species of Rhodococcus, Rhodococcus maanshanensis sp. nov. The type
      strain is strain M712(T) (= AS 4.1720(T) = JCM 11374(T)).

PMID- 12508879
TI  - Two novel psychrotolerant species, Bacillus psychrotolerans sp. nov. and Bacillus
      psychrodurans sp. nov., which contain ornithine in their cell walls.
AB  - Eleven psychrotolerant Bacillus strains with ornithine as diamino acid in
      position 3 of the peptide side chain of the cell wall and a G+C range of 35.7
      38.4 mol% were characterized taxonomically. DNA-DNA hybridization studies
      confirmed previously physiologically established groups. High DNA-binding values
      (> 70%) were found within groups I A (consisting of the type strain of Bacillus
      insolitus DSM 5(T) and Bacillus insolitus DSM 2272), I B (consisting of isolates
      3H1(T0, 71H1, 84E1, 87H2 and 4H2) and I C (consisting of isolates 68E39T), 61E1,
      4E3 and 67E1). Low DNA-binding values (< 60%) were revealed between the three
      groups. Consequently, strains of groups I B and I C were considered as being
      representatives of new psychrotolerant species. For group I B strains the name
      Bacillus psychrotolerans sp. nov. is proposed with the type strain 3H1(T) (= DSM
      11706(T) = NCIMB 13838(T)) and for group I C strains the name Bacillus
      psychrodurans sp. nov. is proposed with the type strain 68E3(T) (= DSM 11713(T) =
      NCIMB 13837(T)).

PMID- 12508880
TI  - Mycobacterium lacus sp. nov., a novel slowly growing, non-chromogenic clinical
      isolate.
AB  - A strain of a novel non-chromogenic mycobacterium was isolated from synovial
      tissue from a 68-year-old female with bursitis of her right elbow. The slowly
      growing strain had a unique PCR-restriction enzyme analysis (PRA) profile of the
      hsp65 gene and 16S rRNA gene sequence in comparison with other mycobacterium
      species. The most closely related species, as determined by 16S rRNA gene
      sequence analysis, are Mycobacterium malmoense, Mycobacterium marinum,
      Mycobacterium ulcerans and members of the Mycobacterium tuberculosis complex. The
      HPLC and biochemical profiles resembled those of Mycobacterium gastri, although
      differences were noted in the peak-height ratio of the HPLC pattern and the
      nitrate and pyrazinamidase tests. On the basis of PRA, HPLC, biochemical and 16S
      rRNA gene sequence analyses, the name Mycobacterium lacus sp. nov. is proposed
      for this potential pathogen. The type strain is strain NRCM 00-255(T) (= ATCC BAA
      323(T) = DSM 44577(T)).

PMID- 12508881
TI  - Growth requirements and fermentation products of Fusobacterium prausnitzii, and a
      proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov.
AB  - Two newly isolated strains of obligately anaerobic bacteria from human faeces are
      shown here to be related to Fusobacterium prausnitzii, which is regarded as one
      of the most abundant colonizers of the human colon. These strains, along with
      Fusobacterium prausnitzii ATCC 27768(T) and 27766, are non-motile and produce
      butyrate, formate and lactate, but not hydrogen as fermentation products. A new
      finding is that all four strains produce D-lactate, but not L-lactate. The
      strains have a requirement for acetate in the growth medium and this may account
      for the previously reported requirement for rumen fluid. The DNA G+C content of
      the four strains is 47-57 mol%. Together with phylogenetic analysis based on 16S
      rRNA sequencing, this establishes that Fusobacterium prausnitzii strains are only
      distantly related to Fusobacterium sensu stricto and are more closely related to
      members of Clostridium cluster IV (the Clostridium leptum group). It is proposed
      that a new genus, Faecalibacterium gen. nov. be created; this genus should
      include Faecalibacterium prausnitzii gen. nov., comb. nov. ATCC 27768(T) (= NCIMB
      13872(T)) (formerly Fusobacterium prausnitzii) as the type species together with
      ATCC 27766 and the newly isolated strains A2-165 and L2-6.

PMID- 12508882
TI  - Paenibacillus brasilensis sp. nov., a novel nitrogen-fixing species isolated from
      the maize rhizosphere in Brazil.
AB  - Sixteen nitrogen-fixing strains isolated from the rhizosphere of maize planted in
      Cerrado soil, Brazil, which showed morphological and biochemical characteristics
      similar to the gas-forming Paenibacillus spp., were phenotypically and
      genetically characterized. Their identification as members of the genus
      Paenibacillus was confirmed by using specific primers based on the 16S rRNA gene.
      SDS-PAGE of whole-cell proteins, API 50CH, morphological and biochemical tests,
      amplified rDNA-restriction analysis (ARDRA), DNA-relatedness analyses, denaturing
      gradient gel electrophoresis (DGGE) and 16S rRNA gene sequence determinations
      were performed to characterize the novel isolates and to compare them to strains
      of other nitrogen-fixing Paenibacillus spp. Phenotypic analyses showed that the
      16 strains were very homogeneous and shared a high level of relatedness with
      Paenibacillus polymyxa and Paenibacillus peoriae. However, none of the novel
      isolates was able to ferment glycerol (positive test for P. polymyxa), L
      arabinose or D-xylose (positive tests for P. polymyxa and P. peoriae) or utilize
      succinate (positive test for P. peoriae). Genetic approaches also indicated a
      high level of similarity among the novel isolates and P. polymyxa and P. peoriae,
      but the novel strains clearly could not be assigned to either of these two
      recognized species. On the basis of the features presented in this study, the 16
      novel isolates were considered to represent members of a novel species within the
      genus Paenibacillus, for which the name Paenibacillus brasilensis is proposed.
      The type strain is PB1 72(T) (= ATCC BAA-413(T) = DSM 14914(T)).

PMID- 12508883
TI  - Pseudoxanthomonas taiwanensis sp. nov., a novel thermophilic, N2O-producing
      species isolated from hot springs.
AB  - Two novel thermophilic bacterial strains, with an optimum growth temperature of
      between 50 and 60 degrees C, were isolated from the Chi-ban Hot Springs in
      eastern Taiwan. Strains CB-225 and CB-226(T) were aerobic, thermophilic, non
      sporulating, yellow-pigmented heterotrophic organisms. These strains exhibited an
      unusual denitrification reaction, reducing nitrite, but not nitrate, with the
      production of N2O only. On the basis of a phylogenetic analysis of 16S rDNA
      sequences, DNA-DNA similarity data, morphological, physiological and biochemical
      characteristics, and fatty acid compositions, it was found that the novel strains
      belonged to the genus Pseudoxanthomonas and represented a novel species within
      this genus, for which the name Pseudoxanthomonas taiwanensis is proposed; the
      type strain is CB-226(T) (= ATCC BAA-404(T) = CCRC 17172(T)). P. taiwanensis
      differs from the only member of the genus Pseudoxanthomonas, the mesophilic
      species Pseudoxanthomonas broegbernensis, in that it exhibits a higher growth
      temperature and different morphological characteristics, such as the absence of
      polar flagella.

PMID- 12508884
TI  - Streptomyces avermectinius sp. nov., an avermectin-producing strain.
AB  - We propose the establishment of a new species, Streptomyces avermectinius, based
      on characterization of strain MA-4680(T) and morphological and phylogenetic
      comparisons with closely related members of the genus Streptomyces. The 16S rDNA
      sequence was obtained from this strain and used to place it among Streptomyces
      species using the variable alpha region and the nearly complete 16S rDNA
      sequence. Four Streptomyces species were selected as related species from
      phenotypic data, three species from phylogenetic databases on alpha region
      sequences and two species from phylogenetic data using nearly complete 16S rDNA
      sequences. Analysis of DNA-DNA hybridization tests distinguished strain MA
      4680(T) from these eight Streptomyces species. The type strain is strain MA
      4680(T) (= ATCC 31267(T) = NRRL 8165(T)).

PMID- 12508885
TI  - Crossiella equi sp. nov., isolated from equine placentas.
AB  - Over the course of the past decade, actinomycetes have been isolated from the
      placentas of horses diagnosed with nocardioform placentitis. The incidence of
      this infection has generally been low, with typically no more than 30 animals
      affected in most years, but the incidence increased through 1999, with placentas
      from 144 mares found to be infected. Approximately half of the cases result in
      loss of the foal. A typical actinomycete with branching mycelium was isolated
      from placental lesions, and a comparison of the sequence of the 16S rDNA gene
      against the public databases indicated a relationship to members of the suborder
      Pseudonocardineae. Phylogenetic analysis of representative isolates revealed a
      close relationship to Crossiella cryophila, and subsequent polyphasic comparisons
      determined that these isolates represent a novel species of Crossiella, for which
      the name Crossiella equi sp. nov. is proposed, with strain LDDC 22291-98(T) (=
      NRRL B-24104(T) = DSM 44580(T)) as the type strain.

PMID- 12508886
TI  - Thioalkalispira microaerophila gen. nov., sp. nov., a novel lithoautotrophic,
      sulfur-oxidizing bacterium from a soda lake.
AB  - An anaerobic enrichment medium (pH 10) with thiosulfate as electron donor and
      nitrate as electron acceptor was inoculated with sediment from soda lake Fazda
      (Wadi Natrun, Egypt); a novel strain, ALEN 1(T), was isolated from the subsequent
      enrichment culture. Cells of strain ALEN 1(T) had a spiral morphology (0.3-0.45 x
      1-4 microm), were motile and had a single polar flagellum. Sphaeroplasts were
      formed by the cells and were rapidly lysed during prolonged aerobic incubation of
      cultures. Cells of strain ALEN 1(T) contained a membrane-associated yellow
      pigment. The metabolism of this novel organism was obligately
      chemolithoautotrophic, and thiosulfate or sulfide were utilized as electron
      donors. Washed cells of strain ALEN 1(T) oxidized thiosulfate, sulfide,
      polysulfide and elemental sulfur to sulfate. Best growth was observed when the
      strain was grown under micro-oxic conditions (1-2% O2 in gas phase), whereas
      growth was inhibited under fully oxic conditions. Nitrate was reduced to nitrite
      without growth of the novel organism, but other nitrogen oxides were not utilized
      as electron acceptors. Strain ALEN 1(T) was alkaliphilic and moderately
      halophilic. It grew between pH 8 and 10.4 (optimum around pH 10) with a salt
      concentration of between 0.3 and 1.5 M Na+ (optimum 0-5 M). The maximum growth
      rate (0.08 h(-1)) of the organism was achieved in a thiosulfate-limited micro
      oxic continuous culture (pH 10). Phylogenetic analyses of the 16S rDNA sequences
      of strain ALEN 1(T) and its closest relatives demonstrated that this strain
      formed a deep branch within the gamma-Proteobacteria, with no obvious association
      to any described cluster of species/genera. On the basis of its unique
      physiological properties and distinct phylogenetic position, it is proposed that
      strain ALEN 1(T) (= DSM 14786(T) = UNICEM 212(T)) represents a novel genus within
      the gamma-Proteobacteria, for which the name Thioalkalispira is proposed. It is
      also proposed that the type species of this novel genus be named Thioalkalispira
      microaerophila.

PMID- 12508887
TI  - Pseudomonas chloritidismutans sp. nov., a non-denitrifying, chlorate-reducing
      bacterium.
AB  - A Gram-negative, facultatively anaerobic, rod-shaped, dissimilatory chlorate
      reducing bacterium, strain AW-1(T), was isolated from biomass of an anaerobic
      chlorate-reducing bioreactor. Phylogenetic analysis of the 16S rDNA sequence
      showed 100% sequence similarity to Pseudomonas stutzeri DSM 50227 and 98.6%
      sequence similarity to the type strain of P. stutzeri (DSM 5190(T)). The species
      P. stutzeri possesses a high degree of genotypic and phenotypic heterogeneity.
      Therefore, eight genomic groups, termed genomovars, have been proposed based upon
      deltaTm values, which were used to evaluate the quality of the pairing within
      heteroduplexes formed by DNA-DNA hybridization. In this study, DNA-DNA
      hybridization between strain AW-1(T) and P. stutzeri strains DSM 50227 and DSM
      5190(T) revealed respectively 80.5 and 56.5% similarity. DNA-DNA hybridization
      between P. stutzeri strains DSM 50227 and DSM 5190(T) revealed 48.4% similarity.
      DNA-DNA hybridization indicated that strain AW-1(T) is not related at the species
      level to the type strain of P. stutzeri. However, strain AW-1(T) and P. stutzeri
      DSM 50227 are related at the species level. The physiological and biochemical
      properties of strain AW-1(T) and the two P. stutzeri strains were compared. A
      common characteristic of P. stutzeri strains is the ability to denitrify.
      However, in growth experiments, strain AW-1(T) could use only chlorate or oxygen
      as an electron acceptor and not nitrate, perchlorate or bromate. Strain AW-1(T)
      is the first chlorate-reducing bacterium described that does not possess another
      oxyanion-reduction pathway. Cell extracts of strain AW-1(T) showed chlorate and
      bromate reductase activities but not nitrate reductase activity. P. stutzeri
      strains DSM 50227 and DSM 5190(T) could use nitrate or oxygen as an electron
      acceptor, but not chlorate. Chlorate reductase activity, in addition to nitrate
      reductase activity, was detected in cell extracts of both P. stutzeri strains.
      Chlorite dismutase activity was absent in extracts of both P. stutzeri strains
      but was present in extracts of strain AW-1(T). Based on the hybridization
      experiments and the physiological and biochemical data, it is proposed that
      strain AW-1(T) be classified as a novel species of Pseudomonas, Pseudomonas
      chloritidismutans sp. nov. The type strain is strain AW-1(T) (= DSM 13592(T) =
      ATCC BAA-443(T)).

PMID- 12508888
TI  - Phylogeny of Maricaulis Abraham et al. 1999 and proposal of Maricaulis
      virginensis sp. nov., M. parjimensis sp. nov., M. washingtonensis sp. nov. and M.
      salignorans sp. nov.
AB  - Thirteen marine bacteria isolated from different locations, belonging to the
      genus Maricaulis, were characterized by 16S rRNA gene sequencing, DNA-DNA
      hybridizations and analysis of the internally transcribed 16S-23S rDNA spacer
      (ITS1) region, analysis of fatty acids from total lipids, mass spectrometry of
      polar lipids and determination of temperature and NaCl tolerances. The data
      obtained led to the identification of five new sulfoquinovosyl diacylglycerols,
      using tandem mass spectrometry, and the fragmentation patterns of the individual
      compounds. Four novel species were identified and described as Maricaulis
      virginensis sp. nov. (type strain VKM B-1 5139T)), Maricaulis parjimensis sp.
      nov. (type strain MCS 25(T)), Maricaulis washingtonensis sp. nov. (type strain
      MCS 6(T)) and Maricaulis salignorans sp. nov. (type strain MCS 18(T)). They
      differ in their temperature and salt tolerances and can be differentiated by
      their polar lipids and fatty acid patterns, as well as their ITS1 and 16S rRNA
      gene sequences.

PMID- 12508889
TI  - Pseudomonas thermotolerans sp. nov., a thermotolerant species of the genus
      Pseudomonas sensu stricto.
AB  - A bacterium, strain CM3(T), which has an optimal growth temperature of
      approximately 47 degrees C and a maximal growth temperature of 55 degrees C, was
      isolated from a hexadecane enrichment culture, obtained from a sample of the
      industrial cooking water of a cork-processing plant. 16S rRNA gene sequence
      analysis demonstrated that this Gram-negative, aerobic, rod-shaped bacterium is
      related to species of the genus Pseudomonas. Phosphatidylethanolamine and
      phosphatidylglycerol were the major polar lipids of this isolate and the total
      fatty acid methyl ester profile revealed predominantly C16:1 and C18:1 at a
      growth temperature of 25 degrees C, whereas, at a growth temperature of 50
      degrees C, C16:0 was the dominant fatty acid. This is the first report of a
      species of Pseudomonas sensu stricto that may be considered to be truly
      thermotolerant. Isolate CM3(T) (= DSM 14292(T) = LMG 21284(T)) represents the
      type strain of a novel species of the genus Pseudomonas, named Pseudomonas
      thermotolerans sp. nov.

PMID- 12508890
TI  - Shewanella denitrificans sp. nov., a vigorously denitrifying bacterium isolated
      from the oxic-anoxic interface of the Gotland Deep in the central Baltic Sea.
AB  - Three strains of denitrifying estuarine bacteria, OS217(T), 05220 and OS226, were
      characterized for their physiological and biochemical features, fatty acid
      profiles and their phylogenetic position based on 16S rDNA sequences. The strains
      were isolated from the oxic-anoxic interface of an anoxic basin of the central
      Baltic Sea. Phylogenetic analyses of the 16S rDNA sequences revealed a clear
      affiliation with members of the genus Shewanella of the gamma-Proteobacteria. The
      closest sequence similarity was seen with Shewanella baltica, Shewanella
      putrefaciens and Shewanella frigidimarina (95-96%). The dominant fatty acids were
      16:1omega7c, 15:0 iso, 16:0 and 13:0 iso. The G+C content of the DNA ranged from
      46.8 to 48.1 mol%. The strains were unpigmented, polarly flagellated, mesophilic,
      facultatively anaerobic and able to use nitrate, nitrite and sulphite as electron
      acceptors. Growth was observed at salinities from 0 to 6%, with an optimum
      between 1 and 3%. According to their morphology, physiology, fatty acid
      composition and 16S rRNA sequences, the described bacteria fitted well into the
      genus Shewanella, but could be easily distinguished from the Shewanella species
      described to date. Because of their capacity for vigorous denitrification, the
      name Shewanella denitrificans sp. nov. is suggested for the Baltic isolates, for
      which the type strain is OS217(T) (= DSM 15013(T) = LMG 21692(T)).

PMID- 12508891
TI  - Characterization of rhizobia that nodulate legume species of the genus Lespedeza
      and description of Bradyrhizobium yuanmingense sp. nov.
AB  - Legume species belonging to the genus Lespedeza are annual or perennial herb or
      shrub plants that grow in the northern hemisphere. They are known for the
      formation of root nodules, but little information is available about their
      microsymbionts. In this study, 58 root-nodule isolates from Lespedeza spp.,
      obtained from China and the USA, were characterized using numerical taxonomic
      analysis of phenotypic features, SDS-PAGE analysis of whole-cell proteins, DNA
      DNA hybridization, 16S rRNA gene sequence analysis and cross-nodulation with
      selected legume species. From the results generated using these approaches, it
      was concluded that Lespedeza spp. were promiscuous hosts for rhizobia. Four main
      clusters of bacteria, which included 35 of the strains isolated from Lespedeza
      spp., were defined upon numerical taxonomic analysis; these groups corresponded
      to those determined from analyses of protein electrophoretic and DNA-DNA
      hybridization data. The four clusters were found to define strains belonging to
      one of four species, Sinorhizobium saheli, Bradyrhizobium japonicum,
      Bradyrhizobium elkanii or a novel species of the genus Bradyrhizobium. The
      strains of B. japonicum and B. elkanii were all from the USA soil samples, and
      their representative strains could not nodulate soybean. The seven strains found
      to represent the novel Bradyrhizobium sp. were from China. These were
      differentiated from recognized species of the genus Bradyrhizobium by all of the
      taxonomic methods used here; hence, it is proposed that the novel strains
      isolated from Lespedeza spp. represent a novel species of the genus
      Bradyrhizobium, Bradyrhizobium yuanmingense. The type strain of the novel
      species, CCBAU 10071(T) (= CFNEB 101(T)), formed ineffective nodules on Medicago
      sativa and Melilotus albus but did not nodulate soybean. The other 23 bacterial
      strains isolated from Lespedeza spp. were found to form single branches or small
      groups (two to three strains) that were related to Bradyrhizobium, Mesorhizobium,
      Rhizobium and Sinorhizobium spp. on the basis of numerical taxonomic analysis,
      indicating the possibility that other rhizobial species are also associated with
      Lespedeza spp.

PMID- 12508892
TI  - Rhizobium indigoferae sp. nov. and Sinorhizobium kummerowiae sp. nov.,
      respectively isolated from Indigofera spp. and Kummerowia stipulacea.
AB  - Forty-eight rhizobial isolates from root nodules of Indigofera and Kummerowia,
      two genera of annual or perennial wild legumes growing in the Loess Plateau in
      north-western China, were characterized by a polyphasic approach. Two main
      groups, cluster 1 and cluster 2, were defined based upon the results of numerical
      taxonomy, SDS-PAGE of whole-cell proteins and DNA relatedness. All the isolates
      within cluster 1 were isolated from Indigofera and they were identified as
      Rhizobium strains by 16S rRNA gene analysis. DNA relatedness of 29.5-48.9% was
      obtained among the cluster 1 isolates and the reference strains for defined
      Rhizobium species. Cluster 2 consisted of isolates from Kummerowia stipulacea and
      was identified as belonging to Sinorhizobium by 16S rRNA gene analyses. DNA
      relatedness varied from 5.2 to 41.7% among the isolates of cluster 2 and
      reference strains for Sinorhizobium species. Considering the existence of
      distinctive features among these two groups and related species within the genera
      Rhizobium and Sinorhizobium, we propose two novel species, Rhizobium indigoferae
      sp. nov. for cluster 1, with isolate CCBAU 71714(T) (= AS 1.3046(T)) as the type
      strain, and Sinorhizobium kummerowiae sp. nov. for cluster 2, with isolate CCBAU
      71042(T) (= AS 1.3045(T)) as the type strain.

PMID- 12508893
TI  - Paenibacillus turicensis sp. nov., a novel bacterium harbouring heterogeneities
      between 16S rRNA genes.
AB  - A Gram-positive, facultatively anaerobic, rod-shaped, endospore-forming bacterium
      (strain MOL722(T)) was characterized using phenotypic and molecular methods.
      Fatty acid analysis and biochemical examination indicated that the isolate
      belongs to the Gram-positive bacteria with low DNA G+C content, probably to the
      genus Paenibacillus. Direct sequencing of the 16S rRNA gene showed ambiguities,
      suggesting heterogeneity. Cloned 16S rDNA yielded seven different sequences
      varying at 15 positions, with one being an insertion. The isolate shares 98.5%
      sequence similarity with Paenibacillus sp. P15-9, but less than 94% similarity
      with other paenibacilli and bacilli. Phylogenetic analysis with different treeing
      methods revealed that strain MOL722(T), together with Paenibacillus sp. P15-9,
      forms a novel monophyletic clade within the genus Paenibacillus. Based on
      phenotypic and phylogenetic evidence, it is proposed that the unknown bacterium
      is classified as the novel species Paenibacillus turicensis sp. nov., the type
      strain of which is strain MOL722(T) (= DSM 14349(T) = NCCB 100011(T)).

PMID- 12508894
TI  - Geobacillus toebii sp. nov., a novel thermophilic bacterium isolated from hay
      compost.
AB  - A thermophilic, spore-forming rod isolated from hay compost in Korea was
      subjected to a taxonomic study. The micro-organism, designated strain SK-1(T),
      was identified as being aerobic, Gram-positive, motile and rod-shaped. Growth of
      the isolate was observed at 45-70 degrees C (optimum 60 degrees C) and pH 6.0-9.0
      (optimum pH 7.5). The G+C content of the genomic DNA was 43.9 mol%.
      Chemotaxonomic characteristics of the isolate included the presence of
      mesodiaminopimelic acid in the cell wall and iso-C15:0 and iso-C17:0 as the major
      cellular fatty acids. The predominant isoprenoid quinone was MK-7. The
      chemotaxonomic characteristics of strain SK-1(T) were the same as those of the
      genus Geobacillus. Phylogenetic analysis based on 16S rDNA sequences showed that
      strain SK-1(T) is most closely related to Geobacillus thermoglucosidasius.
      However, the phenotypic properties of strain SK-1(T) were clearly different from
      those of G. thermoglucosidasius. The level of DNA-DNA relatedness between strain
      SK-1(T) and the type strain of G. thermoglucosidasius was 27%. On the basis of
      the phenotypic traits and molecular systematic data, strain SK-1(T) represents a
      novel species within the genus Geobacillus, for which the name Geobacillus toebii
      sp. nov. is proposed. The type strain is strain SK-1(T) (= KCTC 0306BP(T) - DSM
      14590(T)).

PMID- 12508895
TI  - Rothia amarae sp. nov., from sludge of a foul water sewer.
AB  - A Gram-positive bacterium, strain J18(T), isolated from sludge of a foul water
      sewer, was subjected to a polyphasic taxonomic study. Phylogenetic analysis of
      the bacterium based on its 16S rDNA sequence showed that it belongs to the genus
      Rothia and forms a distinct phyletic clade with the type strain of Rothia
      nasimurium. Morphological, physiological and chemotaxonomic characteristics
      supported the assignment of this organism to the genus Rothia and distinguished
      it from the type strains of all validly described Rothia species. Therefore, it
      is proposed that this bacterium be classified in the genus Rothia as Rothia
      amarae sp. nov. The type strain is strain J18(T) (= AS 4.1721(T) = JCM 11375(T)).

PMID- 12508896
TI  - Teredinibacter turnerae gen. nov., sp. nov., a dinitrogen-fixing, cellulolytic,
      endosymbiotic gamma-proteobacterium isolated from the gills of wood-boring
      molluscs (Bivalvia: Teredinidae).
AB  - A cellulolytic, dinitrogen-fixing bacterium isolated from the gill tissue of a
      wood-boring mollusc (shipworm) Lyrodus pedicellatus of the bivalve family
      Teredinidae and 58 additional strains with similar properties, isolated from
      gills of 24 bivalve species representing 9 of 14 genera of Teredinidae, are
      described. The cells are Gram-negative, rigid, rods (0.4-0.6 x 3-6 microm) that
      bear a single polar flagellum. All isolates are capable of chemoheterotrophic
      growth in a simple mineral medium supplemented with cellulose as a sole source of
      carbon and energy. Xylan, pectin, carboxymethylcellulose, cellobiose and a
      variety of sugars and organic acids also support growth. Growth requires addition
      of combined nitrogen when cultures are vigorously aerated, but all isolates fix
      dinitrogen under microaerobic conditions. The pH, temperature and salinity optima
      for growth were determined for six isolates and are approximately 8.5, 30-35
      degrees C and 0.3 M NaCl respectively. The isolates are marine. In addition to
      NaCl, growth requires elevated concentrations of Ca2+ and Mg2+ that reflect the
      chemistry of seawater. The DNA G+C content ranged from 49 to 51 mol%. Four
      isolates were identical with respect to small-subunit rRNA sequence over 891
      positions compared and fall within a unique clade in the gamma-subclass of the
      Proteobacteria. Based on morphological, physiological and phylogenetic
      characteristics and specific symbiotic association with teredinid bivalves, a new
      genus and species, Teredinibacter turnerae gen. nov., sp. nov., is proposed. The
      type strain is T7902(T) (= ATCC 39867(T) = DSM 15152(T)).

PMID- 12508897
TI  - Characterization of a novel halophilic archaeon, Halobiforma haloterrestris gen.
      nov., sp. nov., and transfer of Natronobacterium nitratireducens to Halobiforma
      nitratireducens comb. nov.
AB  - Strain 135(T), a novel red-pigmented, aerobic, extremely halophilic member of the
      Archaea showing rod, coccus and slightly pleomorphic morphology, was isolated
      from hypersaline soil close to Aswan (Egypt). This organism is neutrophilic,
      motile and requires at least 2.2 M NaCl, but no MgCl2, for growth and exhibits
      optimal growth at 42 degrees C. Polar lipid analysis revealed the presence of
      sulfated triglycosyl diether and triglycosyl diether as the sole glycolipids as
      well as the absence of the glycerol diether analogue of phosphatidyl
      glycerosulfate. C20:C20 and C20:C25 core lipids are present in almost equal
      proportions. The G+C content of the DNA is 66.9 mol%. 16S rDNA analysis revealed
      that strain 135(T) was a member of the phyletic group defined by the family
      Halobacteriaceae, but there was a low degree of similarity to other members of
      this family. Highest similarity values of 96.4 and 93.8-94.3% were obtained to
      the 16S rDNA of Natronobacterium nitratireducens and Natronobacterium gregoryi,
      Natronococcus occultus and Natronococcus amylolyticus. Strain 135(T) is able to
      accumulate polyhydroxybutyrate as intracellular reserve material. On the basis of
      the data presented, strain 135(T) should be placed in a new genus, Halobiforma
      gen. nov. as Halobiforma haloterrestris sp. nov. The type strain is strain 135(T)
      (= DSM 13078(T) = JCM 11627(T)). Moreover, the transfer of Natronobacterium
      nitratireducens to Halobiforma nitratireducens comb. nov. is proposed.

PMID- 12508898
TI  - Characterization of Serratia isolates from soil, ecological implications and
      transfer of Serratia proteamaculans subsp. quinovora Grimont et al. 1983 to
      Serratia quinivorans corrig., sp. nov.
AB  - Eleven strains of Serratia were isolated from different soils and the guts of
      invertebrates and characterized by their sensitivity to eight indigenous
      bacteriophages. They were also classified according to bacteriocin production and
      sensitivity, BiOLOG plate and API 20E strip profiles and 16S rRNA sequence
      information. One strain was thus identified as Serratia plymuthica, another as
      Serratia fonticola. The remaining strains were shown to be closely related to
      Serratia proteamaculans subsp. quinovora Grimont et al. 1983 after DNA-DNA cross
      hybridization demonstrated relatedness greater than 70% with the type strain of
      this subspecies. From an ecological perspective, our results illustrated the wide
      variation in sensitivity that closely related Serratia strains have towards
      various indigenous soil phages and that these phages have broad host ranges
      within the genus. Furthermore, the phage and bacteriocin interactions within the
      Serratia strains examined were intricate and did not reflect phylogenetic
      relationships. These results together imply that complex interactions will occur
      in soil within the natural community of Serratia strains and their
      bacteriophages. DNA-DNA cross-hybridization and phenotypic characterization
      showed that S. proteamaculans subsp. quinovora strains formed a cohesive group at
      the species level. It is therefore concluded that these strains should be
      designated as Serratia quinivorans corrig., sp. nov.

PMID- 12508899
TI  - Nocardiopsis metallicus sp. nov., a metal-leaching actinomycete isolated from an
      alkaline slag dump.
AB  - A taxonomic study was carried out on a metal-mobilizing, alkaliphilic bacterium
      from an alkaline slag dump, strain KBS6(T). The strain produced substrate and
      aerial mycelia. Growth occurred in the pH range 7.0-10.5, with an optimum at pH
      8.5. A salt concentration of up to 10% was tolerated, and various organic
      substrates were used for growth. The results of a 16S rDNA sequence comparison
      revealed that strain KBS6(T) belongs to the genus Nocardiopsis. DNA-DNA
      hybridization with the two closest relatives, Nocardiopsis exhalans and
      Nocardiopsis prasina, gave similarity values of 18.2 and 44.1%, respectively,
      which indicated that strain KBS6(T) represents a novel species of the genus
      Nocardiopsis. This is consistent with the morphological, physiological and
      chemotaxonomic data. Because of the ability of this micro-organism to solubilize
      metals, the name Nocardiopsis metallicus sp. nov. is proposed for strain KBS6(T)
      (= DSM 44598(T) = NRRL B-24159(T)), this being the type strain.

PMID- 12508900
TI  - Phylogenetic relationships amongst tetrahymenine ciliates inferred by a
      comparison of telomerase RNAs.
AB  - The phylogenetic relationships between ciliate species in the suborder
      Tetrahymenina, order Hymenostomata, was investigated by comparing their
      telomerase RNA (TER) sequences. This relatively small RNA is an integral part of
      telomerase, the ribonucleoprotein enzyme that catalyses the synthesis of
      telomeric DNA. Despite a relatively rapid rate of primary sequence divergence,
      conserved functional and structural elements within TERs facilitate the accurate
      alignment of truly homologous nucleotides. The tetrahymenine phylogeny derived
      from distance analysis of TER sequences is largely consistent with those based on
      rRNA and histone sequences.

PMID- 12508901
TI  - Cryptococcus statzelliae sp. nov. and three novel strains of Cryptococcus
      victoriae, yeasts isolated from Antarctic soils.
AB  - A morphological and physiological characterization of yeast strains CBS 8908, CBS
      8915, CBS 8920, CBS 8925(T) and CBS 8926, isolated from Antarctic soils, was
      performed. Phylogenetic analyses of the sequences of the D1/D2 regions and the
      adjacent internal transcribed spacer (ITS) regions of the large-subunit rDNA of
      these strains placed them into the Tremellales clade of the Hymenomycetes. The
      sequence data identified strains CBS 8908, CBS 8915 and CBS 8920 as belonging to
      the species Cryptococcus victoriae. Strains CBS 8925(T) and CBS 8926 were found
      to represent an unique clade within the Hymenomycetes, with Dioszegia crocea CBS
      6714(T) being their closest phylogenetic relative. Fatty acid composition and
      proteome fingerprint data for these novel strains were also obtained. No sexual
      state was observed. A novel basidiomycetous species, Cryptococcus statzelliae, is
      proposed for strains CBS 8925(T) and CBS 8926.

PMID- 12508902
TI  - Reclassification of the Sporobolomyces roseus and Sporidiobolus pararoseus
      complexes, with the description of Sporobolomyces phaffii sp. nov.
AB  - More than 50 ballistoconidium-forming yeast strains, isolated from plant leaves
      collected in Yunnan, China, were identified as Sporobolomyces roseus Kluyver &
      van Niel by conventional methods. However, comparison of the internal transcribed
      spacer (ITS) region and 265 rDNA D1/D2 domain sequences indicated that these
      strains represented more than one species. Type or authentic strains of the
      synonyms of Sporobolomyces roseus and the closely related species Sporidiobolus
      pararoseus Fell & Tallman were employed in the rDNA sequence comparison.
      Sporobolomyces boleticola Ramirez, Sporobolomyces pollaccii Verona & Ciferri,
      Sporobolomyces roseus var. madurae Janke and Torulopsis somala Verona were
      confirmed to be conspecific with Sporobolomyces roseus. Another synonym of this
      species, Sporobolomyces salmoneus Derx, was located together with Sporobolomyces
      marcillae Santa Maria in a separate clade. Two synonyms of Sporidiobolus
      pararoseus, Sporobolomyces carnicolor Yamasaki & Fujii (nom. inval.) and
      Sporobolomyces japonicus Iizuka & Goto, were revealed to represent two distinct
      species. The name Sporobolomyces carnicolor is validated, with strain CBS 4215(T)
      as the type strain. A novel species represented by five of the selected Yunnan
      strains was confirmed, for which the name Sporobolomyces phaffii sp. nov. is
      proposed (type strain CH 2.052(T) = AS 2.2137(T) = JCM 11491(T) = CBS 9129(T)).
      This study also indicates that yeast species with similar ITS sequences may have
      quite different D1/D2 sequences.

PMID- 12508903
TI  - Citeromyces siamensis sp. nov., a novel halotolerant yeast isolated in Thailand.
AB  - Two halotolerant yeast strains, H130(T) and H149, were isolated from dry salted
      squid and fermented soybeans, respectively, in Thailand. Both isolates grew by
      multilateral budding, produced asci that had one roughened spherical ascospore
      and contained ubiquinone Q-8. These characteristics were shared by Citeromyces
      matritensis, the only species of the genus Citeromyces. Strains H130(T) and H149
      were differentiated from C matritensis by their ability to assimilate L-sorbose
      and L-lysine and to grow at 37 degrees C. The novel isolates were more tolerant
      to higher concentrations of cations (3 M NaCl or 0.8 M LiCI) and to higher
      osmotic pressure (60% glucose) than C. matritensis. A phylogenetic analysis of
      18S rRNA gene sequence data indicated that the two novel isolates represented a
      sister species to C. matritensis. Furthermore, DNA-DNA hybridization data
      indicated that the isolates were clearly distinct from the type strain of C.
      matritensis (IFO 0954(T). Based on the above characteristics, strains H130(T) and
      H149 are proposed to represent a novel species within the genus Citeromyces,
      Citeromyces siamensis; the type strain is H130(T) (= IFO 11052(T) = JCM 11522(T)
      = TISTR 5777(T) = CBS 9153(T)).

PMID- 12508904
TI  - Necessary corrections to the Approved Lists of Bacterial Names according to Rule
      40d (formerly Rule 46). Request for an opinion.
AB  - According to Rule 40d (formerly Rule 46), the authorship and dates of ten
      subspecies cited in the Approved Lists of Bacterial Names should be corrected. It
      is requested that such changes be approved by the Judicial Commission.

PMID- 12508905
TI  - Replacement therapy in the aging male.
AB  - In the aging male, endocrine changes and decline in endocrine function involve
      tissue responsiveness as well as reduced secretory output from peripheral glands
      and alterations in the central mechanism controlling the temporal organization of
      hormonal release. The latter are likely to be responsible for the dampened
      circadian hormonal and non-hormonal rhythms. These are in part responsible of the
      age dependent decrease of the peripheral levels of T, DHEA, the thyroid hormones,
      GH, IGF-I, and melatonin. These hormonal changes which develop in most men at
      about the age of 50 are in part responsible for the partial endocrine
      deficiencies of aging male (PEDAM). In cases of endocrine deficiencies,
      traditional endocrinology aims at replacing the missing hormone or hormones with
      substitutes. It has been demonstrated that interventions, such as hormone
      replacement therapies and use of antioxidant drugs may favorably influence some
      of the pathological conditions in aging men, by preventing the preventable and
      delaying the inevitable. A comprehensive medical, psycho-social and life-style
      history, a physical examination and laboratory testing are essential for the
      diagnosis and management of PEDAM. Acute, chronic or inter-current diseases must
      be taken into consideration prior to initiating any hormonal substitution
      therapy. Hormone substitution should only be performed by physicians with basic
      knowledge and clinical experience in diagnosis, treatment and monitoring of
      endocrine deficiencies. In the Era of Evidence Based Medicine, we have to
      acknowledge that data on hormone replacement therapy (HRT) in the aging male is
      mostly circumstantial, based on experience in treatment of transitional or
      chronic endocrine deficiencies in young men due to disease or experiments of
      nature. However over the past several years, there has been an increasing
      interest in evaluating whether male HRT might be beneficial for a specific
      category of older men in preventing or delaying some aspects of ageing, and a
      number of prospective studies on hormone replacement therapy in the aging male
      were performed and these are presented in detail.

PMID- 12508907
TI  - Toxic multinodular goiter in the elderly.
AB  - Toxic nodular goiter (TNG) is the most frequent cause of thyrotoxicosis in the
      elderly, specially in iodine deficient areas. Epidemiological studies have shown
      that in iodine deficient areas (Jutland) the incidence of hyperthyroidism is
      significantly higher with respect to areas with normal iodine intake (Iceland)
      and it is due to TNG. A careful epidemiological study recently carried out in
      Pescopagano, in southern Italy, an area characterized by a mild to moderate
      iodine deficiency, indicates that, in its natural history, nodular goiter
      contributes to the development of functional autonomy and eventually
      hyperthyroidism. Somatic activating mutations of the TSH receptor are involved in
      the pathogenesis of TNG. It is supposed that the prolonged iodine deficiency
      associated with chronic TSH stimulation increases the replication of follicular
      thyroid cells, and favor the appearance and expression of mutations of the TSH
      receptor gene. The clinical signs are usually more subtle than those observed in
      Graves' disease: a long phase of subclinical hyperthyroidism (normal circulating
      thyroid hormones and undetectable TSH levels) can precede the appearance of the
      symptoms. Cardiac symptoms are most frequent, (arrhythmia and atrial
      fibrillation). Thyroid scintigraphy in toxic multinodular goiter shows an uneven
      distribution of the radionuclide with multiple hyperfunctioning nodules and cold
      nodules. Thyroid US shows goiter with inhomogeneous solid nodules often with ill
      defined borders. The treatment with antithyroid drug does not allow a permanent
      remission of hyperthyroidism, but its use is indicated to achieve euthyroidism
      before the definitive treatment. The definitive treatment is radioiodine or
      thyroidectomy.

PMID- 12508906
TI  - Biomarkers of frailty in older persons.
AB  - Trajectories of health and functioning with age show extreme variability among
      different individuals. Normal aging implies a progressive decline of
      physiological reserve and ability to compensate, but it is compatible with
      autonomy over the entire life span. In frail, older persons the decline in
      functional reserve is accelerated and compensatory mechanisms start failing, with
      high risk of homeostasis disruption and consequent negative health outcomes.
      Frailty is currently conceptualized as an age-related alteration in physiology
      and pathology that results into a typical constellation of signs and symptoms.
      Although current attempts to identify frail, older individuals for clinical
      purposes are based on measures of mobility and motor performance, candidate
      biological markers that may characterize the frailty syndrome start to emerge in
      the literature. These potential markers include, but are not limited to, soluble
      mediators of the inflammatory response, hormones, free radicals, antioxidants and
      macro- and micro-nutrients. This is a research area undergoing a rapid, dynamic
      development that may profit from new ways of defining disability outcomes in
      epidemiological studies of the elderly.

PMID- 12508908
TI  - Hypothalamic-pituitary-adrenal axis impairment in the pathogenesis of rheumatoid
      arthritis and polymyalgia rheumatica.
AB  - Stressful/inflammatory conditions activate the immune system and subsequently the
      hypothalamic-pituitary-adrenal (HPA) axis through the central and peripheral
      production of cytokines such as IL-6 and TNF-alpha. A relative adrenal
      hypofunction, as evidenced by inappropriately normal F levels and reduced DHEAS
      levels, has been recently claimed to play a causative role in the pathogenesis of
      autoimmune/inflammatory diseases such as rheumatoid arthritis (RA) and
      polymyalgia rheumatica (PMR). Thus, we evaluated baseline levels of adrenal
      androgens, IL-6 and IL-12 together with HPA axis challenge by ovine CRH and low
      dose ACTH in premenopausal RA women and aged PMR women. In addition, adrenal
      steroids, IL-6, and acute-phase reactant levels were measured at baseline and
      during 12 months of glucocorticoid tapering regimen in a cohort of PMR patients.
      Reduced DHEAS levels (p<0.05) associated to increased (p<0.05) IL-6 and IL-12
      levels were found in RA patients as compared to controls (C). Irrespective of the
      inflammatory condition, basal and stimulated cortisol levels in RA were similar
      to C, whereas DHEA secretion after ACTH testing was significantly (p<0.01)
      reduced. During HPA challenge, F responses in PMR patients proved inadequate in
      the setting of the inflammatory status, confirmed by increased IL-6 levels. In
      addition, these patients showed significantly (p<0.05) increased 17
      hydroxyprogesterone (17-OHP) responses after ACTH testing as compared to C. The
      longitudinal study in PMR patients showed that glucocorticoid therapy leads to a
      stable reduction of IL-6 and of acute-phase reactant levels, which persist even
      after glucocorticoid tapering. Our data show an inadequate adrenal secretion in
      RA and PMR, both characterized by increased levels of HPA axis-stimulating
      cytokines. The reduced basal levels of DHEAS in RA might be ascribed to a reduced
      biosynthesis as consequence of a cytokine-induced impairment of P450 17.20-lyase
      activity. In PMR, the ACTH-induced enhanced 17-OHP levels suggest a partial age-
      and cytokine-induced impairment of the P450 21 beta-hydroxylase, which eventually
      leads to inadequate glucocorticoid production. The clinical and biochemical
      improvement observed after glucocorticoid therapy in patient with RA and PMR,
      might thus be attributed to a direct dampening of pro-inflammatory factors as
      well as to the restoration of the steroid milieu. Given its multifaceted
      properties, including the ability to counteract the negative side effects of
      glucocorticoids, the therapeutical administration of DHEA might be considered in
      these pathologies, provided its safety is proved.

PMID- 12508909
TI  - Pituitary function in chronic heart failure in the elderly.
AB  - Heart failure is a complex syndrome characterized by the activation of
      hemodynamic, immunologic and neurohormonal systems, which have beneficial effects
      in the short run, but will ultimately lead to secondary end-organ damage with
      worsening of LV remodeling and subsequent cardiac decompensation. A very
      important role seems to be played by modifications of the pituitary hormone
      systems. Due to the neurohormonal activation there is an increase in the activity
      in the renin angiotensin system, in the adrenergic nervous system, and in the
      cytokine system. In heart failure there is a decrease in many anabolic hormones,
      such as a decrease of GH and IGF-I, of DHEA/DHEAS with normal or increased F, and
      a decrease of LH and sex steroids, resulting in an important catabolic drive,
      capable of contributing to the development of cardiac failure and to sarcopenia
      and/or cachexia, frequently observed in the advanced stages of the disease.
      However, these hormone alterations have been described in relatively young
      patients with chronic heart failure, since the mean age of all the subjects
      studied was of about 60 yr and none of the studies have specifically addressed
      this issue in the very old patients, who represent the largest portion of
      population affected by this pathological condition. The role of hormone
      replacement therapy needs to be verified in a population of elderly patients with
      heart failure.

PMID- 12508910
TI  - Adrenopause: an imbalance between dehydroepiandrosterone (DHEA) and cortisol
      secretion.
AB  - Several clinical signs might be related to the decline of DHEA secretion in aged
      people: sarcopenia, osteopenia, atherosclerosis progression, impairment of
      cognitive and affective performances, deterioration of immunocompetence are the
      most significant evidences. In addition, in aged people this clinical condition
      might be worsened by the concomitant relative glucocorticoid excess which
      develops in an age related manner. All together, these clinical signs construct
      the corpus of a syndrome named adrenopause. DHEA replacement therapy might find
      its indication besides the obvious condition of primary and secondary
      corticoadrenal insufficiency in those aged patients with typical signs of
      adrenopause accompanied by magnified decline of DHEA and relative excess of
      cortisol. Two further indications for aged patients might be represented by those
      with chronic inflammatory diseases, especially when long term treated with
      glucocorticoids and those who undergo surgical procedures.

PMID- 12508911
TI  - Evaluation of GH deficiency by GHRH+arginine test and IGF-I levels in a large
      population of young, middle-aged and elderly patients who had undergone
      neurosurgery for tumor masses in the hypothalamus-pituitary area.

PMID- 12508912
TI  - GH deficiency syndrome in elderly patients.

PMID- 12508913
TI  - Age-related variations of the GH response to GH secretagogues in humans.

PMID- 12508914
TI  - H9c2 cardiac muscle cells express insulin-like growth factor binding protein-3
      (IGFBP-3).

PMID- 12508915
TI  - Impairment of secretory pattern of IGF-I from lymphomononuclear cells in aging
      and dementia of the Alzheimer's and vascular type.

PMID- 12508916
TI  - GH but not IGF-I hypersecretion in acromegaly is generally attenuated in elderly
      acromegalics.

PMID- 12508917
TI  - The nutritional status has no major role in the age-related reduction of IGF-I
      secretion.

PMID- 12508918
TI  - IGF system in acute ischemic stroke.

PMID- 12508919
TI  - Functioning and non-functioning pituitary adenomas in 173 adult and elderly
      patients.

PMID- 12508920
TI  - Thyroid function in old and very old healthy subjects.

PMID- 12508921
TI  - The negative role of subclinical thyrotoxicosis on the outcome of hospitalized
      geriatric patients.

PMID- 12508922
TI  - The aging thyroid in a mild to moderate iodine deficient area of Italy.

PMID- 12508923
TI  - Evaluation of thyroid function in outpatients affected by dementia.

PMID- 12508924
TI  - Thyroid function and goiter recurrence after thyroid lobectomy in elderly
      subjects.

PMID- 12508925
TI  - Low T3 syndrome and outcome in elderly hospitalized geriatric patients.

PMID- 12508926
TI  - Incidence of subclinical hypothyroidism and its influence on cognitive
      performance and on metabolic aspects in an hospitalized geriatric population.

PMID- 12508927
TI  - Twenty-four-hour urinary cortisol levels in Alzheimer disease and in mild
      cognitive impairment.

PMID- 12508928
TI  - DHEA, a selective glucocorticoid receptor antagonist: its role in immune system
      regulation and metabolism.

PMID- 12508929
TI  - Serum total antioxidant capacity, DHEAS and IGF-I in healthy centenarian
      subjects.

PMID- 12508930
TI  - Adrenal sensitivity to ACTH1-24 as function of age, body weight and pituitary
      function.

PMID- 12508931
TI  - Decreased DHEAS secretion in patients with chronic inflammatory diseases treated
      with glucocorticoids.

PMID- 12508932
TI  - Gonadal function changes in healthy, aging men.

PMID- 12508933
TI  - Sexual dysfunction in middle-aged couples: an andrological approach in relation
      to hormone replacement therapy of the partners.

PMID- 12508934
TI  - Vascular effects of raloxifene in post-menopausal women.

PMID- 12508935
TI  - Raloxifene and pituitary secretion in post-menopausal women.

PMID- 12508936
TI  - Osteoporosis treatment in elderly hyperthyroid male patients.

PMID- 12508937
TI  - Antioxidants and bone turnover in involutional osteoporosis.

PMID- 12508938
TI  - Medical treatment of male osteoporosis.

PMID- 12508939
TI  - Age-related endocrine and metabolic changes in simple obesity.

PMID- 12508940
TI  - Modifications of blood pressure and IGF-I levels after weight loss in obesity.

PMID- 12508941
TI  - Insulin resistance, plasma PAI-1 levels and PAI-1 gene polymorphism in healthy
      centenarians.

PMID- 12508942
TI  - Longevity and diabetes: a multidimensional assessment.

PMID- 12508943
TI  - Obesity.

PMID- 12508944
TI  - Prevalence and time trends of obesity in Europe.

PMID- 12508945
TI  - Adipocyte differentiation and transdifferentiation: plasticity of the adipose
      organ.
AB  - In mammals, the adipose organ is a multi-depot organ made of two tissue types,
      the white and brown adipose tissues, which collaborate in partitioning the energy
      contained in lipids between thermogenesis and the other metabolic functions. It
      consists of several sc and visceral depots. Some areas of these depots are brown
      and correspond to brown adipose tissue, while many are white and correspond to
      white adipose tissue. White areas contain a variable amount of brown adipocytes
      and their number varies with age, strain and environmental conditions. Brown and
      white adipocyte are morphologically different. At light microscopy level, brown
      adipocytes have cytoplasmic lipids arranged as numerous small droplets
      (multilocularity), while white adipocytes have cytoplasmic lipids arranged in a
      unique vacuole (unilocularity). Ultrastructurally, brown adipocytes have numerous
      big mitochondria packed with cristae and containing the thermogenic uncoupling
      protein 1 (UCP1). In vivo and in vitro studies have shown that the
      differentiation process of brown and white adipocytes shows distinctive features.
      Nevertheless, the origin of the adipocyte precursor is still unknown. Recent data
      have stressed the plasticity of the adipose organ in adult animals. Indeed, under
      peculiar conditions fully differentiated, white adipocytes can transdifferentiate
      into brown adipocytes, and viceversa. The ability of the adipose organ to
      interconvert its main cytotypes in order to meet changing metabolic needs is
      highly pertinent to the physiopathology of obesity and related to therapeutic
      strategies.

PMID- 12508947
TI  - Adipose tissue hormones.
AB  - It is now widely accepted that white adipose tissue (WAT) secretes a number of
      peptide hormones, including leptin, several cytokines, adipsin and acylation
      stimulating protein (ASP), angiotensinogen, plasminogen activator inhibitor-1
      (PAI-1), adiponectin, resistin etc., and also produces steroids hormones. This
      newly discovered secretory function has shifted our view of WAT, which is no
      longer considered only an energy storage tissue but a major endocrine organ, at
      the heart of a complex network influencing energy homeostasis, glucose and lipid
      metabolism, vascular homeostasis, immune response and even reproduction.
      Virtually all known adipose secreted proteins are dysregulated when the WAT mass
      is markedly altered, either increased in the obese state or decreased in
      lipoatrophy. This strongly implicates adipose-secreted products in the
      ethiopathology and/or complications of both obesity and cachexia. This review
      discusses the physiological relevance of adipose secretion by focusing on protein
      and steroid hormones. Regulation of WAT secretion by the major regulatory factors
      impinging on the adipocytes, i.e. insulin, glucocorticoids, catecholamines and
      thiazolidinediones (TZD) will be addressed. The rationale for therapeutic
      strategies aimed at compensating adverse effects resulting from overproduction or
      lack of a specific adipose secretory product will be discussed.

PMID- 12508948
TI  - Old and new determinants in the regulation of energy expenditure.
AB  - Bw gain is controlled by energy intake on one hand and expenditure on the other.
      The components of energy expenditure are basal metabolism, exercise induced
      thermogenesis and adaptive thermogenesis. In this short review we shall discuss
      the main determinants of adaptive thermogenesis.

PMID- 12508946
TI  - Neuroendocrine regulation of eating behavior.
AB  - The dual center hypothesis in the central control of energy balance originates
      from the first observations performed more than 5 decades ago with brain
      lesioning and stimulation experiments. On the basis of these studies the "satiety
      center" was located in the ventromedial hypothalamic nucleus, since lesions of
      this region caused overfeeding and excessive weight gain, while its electrical
      stimulation suppressed eating. On the contrary, lesioning or stimulation of the
      lateral hypothalamus elicited the opposite set of responses, thus leading to the
      conclusion that this area represented the "feeding center". The subsequent
      expansion of our knowledge of specific neuronal subpopulations involved in energy
      homeostasis has replaced the notion of specific "centers" controlling energy
      balance with that of discrete neuronal pathways fully integrated in a more
      complex neuronal network. The advancement of our knowledge on the anatomical
      structure and the function of the hypothalamic regions reveals the great
      complexity of this system. Given the aim of this review, we will focus on the
      major structures involved in the control of energy balance.

PMID- 12508949
TI  - Lessons in obesity from transgenic animals.
AB  - Many genetic manipulations have created models of obesity, leanness or resistance
      to dietary obesity in mice, often providing insights into molecular mechanisms
      that affect energy balance, and new targets for anti-obesity drugs. Since many
      genes can affect energy balance in mice, polymorphisms in many genes may also
      contribute to obesity in humans, and there may be many causes of primary leptin
      resistance. Secondary leptin resistance (due to high leptin levels) can be
      investigated by combining the ob mutation with other obesity genes. Some
      transgenic mice have failed to display the expected phenotype, or have even been
      obese when leanness was expected. Compensatory changes in the expression of other
      genes during development, or opposing influences of the gene on energy balance,
      especially in global knockout mice, may offer explanations for such findings.
      Obesity has been separated from insulin resistance in some transgenic strains,
      providing new insights into the mechanisms that usually link these phenotypes. It
      has also been shown that in some transgenic mice, obesity develops without
      hyperphagia, or leanness without hypophagia, demonstrating that generalised
      physiological explanations for obesity in individual humans may be inappropriate.
      Possibly the most important transgenic model of obesity so far created is the
      Type 1 11beta-hydroxysteroid dehydrogenase over-expressing mouse, since this
      models the metabolic syndrome in humans. The perspectives into obesity offered by
      transgenic mouse models should assist clinical researchers in the design and
      interpretation of their studies in human obesity.

PMID- 12508950
TI  - Metabolic impact of body fat distribution.
AB  - Many studies have shown that fat distribution influences metabolism independently
      of the effects of total body fat stores. The accumulation of fat in the abdominal
      area, particularly in the visceral fat compartment, seems to be associated with
      an increased risk to display complications such as insulin resistance, diabetes,
      dyslipidemias and atherosclerosis. As reviewed in this paper, the mechanisms
      explaining this impact of fat distribution is not clearly established, although
      evidence suggests that free-fatty acids, leptin, TNF-alpha, PPAR-gamma, and F are
      directly or indirectly involved in this process. Despite a lot of research has
      yet to be performed to mechanistically characterize the impact of visceral fat on
      the metabolic profile, there is enough consensus in the literature about its
      effect to justify its consideration in a clinical setting. In this regard, the
      use of waist circumference as a clinical marker of variations in visceral fat is
      highly relevant and should be encouraged. This review also presents an
      evolutionary perspective according to which body fat gain would have been and may
      still remain an adaptation that helps to deal with stress and inflammation.

PMID- 12508951
TI  - Establishing body composition in obesity.
AB  - The field of human body composition research is reaching a mature stage in its
      development. Quantifying the main body components is integral to the study of
      growth, as the assessment of human physical characteristics is important both in
      anthropological and medical fields. This article will focus on body composition
      methodology. Specifically, our attention is aimed at estimates of body fatness.
      An overview is first provided of the five-level model of body composition as it
      relates to measures of fatness. We then provide general concepts related to
      techniques for estimating body composition. Finally, we briefly discuss the
      measurement of adipose tissue distribution.

PMID- 12508952
TI  - Adrenal and gonadal function in obesity.
AB  - Obesity is associated with multiple alterations of the endocrine systems,
      including abnormal circulating blood hormone concentrations, due to changes in
      their pattern of secretion and/or metabolism, altered hormone transport, and/or
      action at the level of target tissues. There is evidence that alterations of
      endocrine systems regulating sex hormones and corticosteroids may play a crucial
      role in the development of obesity, particularly the abdominal phenotype. Obese
      women are characterized by a condition of sc"functional hyperandrogenism",
      whereas in males, obesity is associated with reduced T levels and decreased LH
      secretory pattern from the pituitary. In addition, in both sexes a dysregulation
      of the hypothalamic-pituitary-adrenal axis has been reported, including both
      neuroendocrine and peripheral alterations, finally leading to inappropriately
      higher than normal exposure to F of peripheral tissues, particularly the visceral
      adipose tissue. By these mechanisms, it can be hypothesized that both visceral
      fat enlargement and alterations of insulin action and associated metabolic
      disturbances may develop, therefore predisposing abdominally obese individuals to
      Type 2 diabetes and cardiovascular disease.

PMID- 12508953
TI  - Coagulation and fibrinolysis abnormalities in obesity.
AB  - Abnormalities in coagulation and haemostasis represent a well-known link between
      obesity and thrombosis (both arterial and venous). Several studies have shown
      that obese patients have higher plasma concentrations of all pro-thrombotic
      factors (fibrinogen, vonWillebrand factor (vWF), and factor VII), as compared to
      non-obese controls, with a positive association with central fat. Similarly,
      plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been
      shown to be higher in obese patients as compared to non-obese controls and to be
      directly correlated with visceral fat. Furthermore, obesity is characterized by
      higher plasma concentrations of anti-thrombotic factors, such as tissue-type
      plasminogen activator (t-PA) and protein C, as compared to non-obese controls,
      the increase in these factors being likely to represent a protective response
      partly counteracting the increase in pro-thrombotic factors. The issue of whether
      adipose tissue contributes directly to plasma PAI-1, its products stimulating
      other cells to produce PAI-1, or whether it primarily contributes indirectly has
      not yet been resolved. It has been proposed that the secretion of interleukin-6
      (IL-6) by adipose tissue, combined with the actions of adipose tissue-expressed
      TNF-alpha in obesity, could underlie the association of insulin resistance with
      endothelial dysfunction, coagulopathy, and coronary heart disease. The role of
      leptin in impairing haemostasis and promoting thrombosis has been recently
      reported. Finally, some hormonal abnormalities (androgen, F, catecholamines)
      associated with the accumulation of body fat may contribute to the impairment of
      coagulative pathway in obesity. As to intervention strategies, dietary (i.e., low
      fat high-fiber diet) and lifestyle (i.e., physical activity) measures have been
      demonstrated to be effective in improving the obesity-associated pro-thrombotic
      risk profile.

PMID- 12508954
TI  - New pharmacological tools for obesity.
AB  - Obesity is a multi-factorial, chronic disorder that has reached epidemic
      proportions in most industrialized countries and is threatening to become a
      global epidemic. Obese patients are at a higher risk from coronary artery
      disease, hypertension, hyperlipidemia, diabetes mellitus, certain cancers,
      cerebrovascular accidents, osteoarthritis, restrictive pulmonary disease, and
      sleep apnea. Obesity is a particularly challenging clinical condition to treat,
      because of its complex pathophysiological basis. Indeed, body weight represents
      the integration of many biological and environmental components. Efforts to
      develop innovative anti-obesity drugs have been recently intensified. In broad
      terms, researchers use different distinct strategies: first, to reduce energy
      intake; second, to increase energy expenditure; third, to alter the partitioning
      of nutrients between fat and lean tissue. In the present review we concentrate on
      the first of these strategies, by underlining the new pharmacological tools which
      are presently studied.

PMID- 12508955
TI  - Cardiovascular risks in obesity.

PMID- 12508956
TI  - Prevention of obesity in childhood.

PMID- 12508957
TI  - Diet and physical activity for obesity: how effective are they?

PMID- 12508958
TI  - Obesity surgery: pros and cons.

PMID- 12508959
TI  - Th1/Th2 balance in childhood idiopathic nephrotic syndrome.
AB  - AIMS: In view of the conflicting evidence of helper T cell type 1 (Th1) or type 2
      (Th2) pattern of cytokine synthesis in childhood idiopathic nephrotic syndrome
      (INS) this study examined the balance of Th1 and Th2 which are characterized by
      intracellular cytokine production of interferon-gamma (IFNgamma) and interleukin
      4 (IL-4), respectively. SUBJECTS AND METHODS: Sixteen children with steroid
      sensitive INS (mean age 9.0 years) were included in this study, together with 15
      healthy normal children (mean age 7.9 years) for the control group. Intracellular
      production of both IFNgamma and IL-4 in helper T cell (CD4+ cell) was
      investigated by a 3-color flow cytometry. RESULTS: The cross-sectional data
      showed no significant differences of percentages of Th0 (IFNgamma+ IL-4+ CD4+
      cell), Th1 (IFNgamma+ lL-4- CD4+ cell) and Th2 (IFNgamma- IL-4+ CD4+ cell) in
      CD4+ cells (p > 0.05). The Th1/Th2 ratio during nephrotic relapse did not differ
      from those during nephrotic remission and in normal healthy children (p > 0.05).
      CONCLUSION: We conclude that there is no significant skew of Th1/Th2 balance in
      childhood INS and that the cardinal immunological abnormality does not lie in
      helper T cells but in other cells, such as suppressor/cytotoxic T cells, natural
      killer cells or monocytes/macrophage. To clarify the pathogenesis of INS,
      comprehensive studies for these cells would be worthwhile.

PMID- 12508960
TI  - Color-coded duplex sonography study of arteriovenous fistulae and pseudoaneurysms
      complicating percutaneous renal allograft biopsy.
AB  - BACKGROUND: The exact incidence and clinical impact of arteriovenous fistulae
      (AVF) and pseudoaneurysms as complications emerging from renal allograft biopsy
      are not well established. We therefore conducted a prospective study using color
      coded duplex sonography (CCDS) to determine the frequency, clinical presentation
      and spontaneous occlusion rate of biopsy-related AVF and pseudoaneurysms in
      kidney transplant recipients. METHODS: We investigated 72 consecutive patients
      undergoing renal allograft biopsy using an automated biopsy technique. CCDS was
      performed before, immediately after and up to more than 6 months after biopsy.
      The diagnosis of AVF was based on the presence of perivascular vibration
      artifacts and detection of typical Doppler curves. Pseudoaneurysms were diagnosed
      based on the presence of"to-and-fro" signals. RESULTS: In 5 patients (6.9%), an
      AVF was detectable before biopsy. Post-biopsy AVF were found in 12 additional
      patients (16.7%) with a spontaneous occlusion rate of 50% within 48 hours and 75%
      after 4 weeks. Three (25%) AVF persisted longer than 1 year. Four patients (5.6%)
      were found to have pseudoaneurysms. All pseudoaneurysms were located closely to
      AVF and closed spontaneously. None of the post-biopsy AVF and pseudoaneurysms
      required specific therapy. In 2 patients (2.8%), allograft biopsy lead to
      significant hemorrhage independent of AVF or pseudoaneurysms. CONCLUSION: These
      results indicate that post-biopsy AVF and pseudoaneurysms are a frequent finding
      after automated renal allograft biopsy. The natural history of these lesions
      shows a high rate of early occlusion. The present data fail to demonstrate
      significant clinical impact of AVF and pseudoaneurysms after renal allograft
      biopsy.

PMID- 12508961
TI  - Doxazosin, but not amlodipine decreases insulin resistance in patients with
      chronic renal failure: a prospective, randomized-controlled study.
AB  - Insulin resistance (IR) in chronic renal failure (CRF) is well-known. In this
      randomized-controlled study, we aimed to compare the effect of doxazosin and
      amlodipine on IR in patients with CRF. Fifteen patients with CRF (male/female:
      5/10, mean age: 46 +/- 13 years) and 9 controls (male/female: 3/6, mean age: 35
      +/- 8 years) were included. Patients and controls had no family history of
      diabetes mellitus. Homeostasis model assessment (HOMA) was calculated as a marker
      of IR. Patients were grouped randomly to doxazosin (n = 8; 2-4 mg/day) and
      amlodipine (n = 7; 5-10 mg/day) arms. Baseline biochemical analysis (fasting
      serum glucose, BUN, creatinine, uric acid, cholesterol and cholesterol subgroups)
      and parameters related with insulin metabolism (insulin, C peptide, HOMA) were
      similar between amlodipine and doxazosin groups. There was no difference in age,
      gender and body mass index among study groups. The follow-up time was 12 weeks.
      Patients with CRF had higher HOMA (1.83 +/- 0.55 vs 1.00 +/- 0.36, p = 0.001),
      fasting insulin (8.06 +/- 1.98 vs 4.46 +/- 1.31 IU/l, p < 0.001) and serum
      triglyceride levels (197 +/- 136 vs 112 +/- 67 mg/dl, p = 0.04) as compared to
      controls. Serum HDL cholesterol levels were significantly lower in patients with
      CRF than controls (40 +/- 10 vs 57 +/- 14 mg/dl, p = 0.02). HOMA significantly
      decreased after doxazosin (1.91 +/- 0.45 vs 1.41 +/- 0.21, p = 0.02), however, no
      difference was found after amlodipine. Also, fasting insulin levels were
      decreased after a 12-week doxazosin therapy from 8.17 +/- 1.22 vs 6.58 +/- 0.84
      IU/l, p = 0.02), but no change was seen after amlodipine. Lipid parameters did
      not significantly change during the study period in 2 groups. No adverse effect
      requiring drug discontinuation was observed during the 12-week period in the
      study groups. In conclusion, doxazosin decreases IR in patients with CRF, whereas
      amlodipine has no effect. This may be of advantage in the treatment of
      hypertension in this group of patients for preventing some long-term complication
      of IR.

PMID- 12508962
TI  - Beta2-microglobulin and hypertensive complications in pregnant women at risk.
AB  - BACKGROUND AND AIM: Beta2-microglobulin (beta2-m) is a polypeptide, which is
      freely filtered through the glomerular basement membrane and absorbed almost
      entirely by the proximal tubular cells. Preeclampsia, a common complication of
      pregnancy, is characterized by pathological renal changes, mainly glomerular
      lesions. The aim of the present study was to investigate whether serum beta2-m
      measured in the early stages of pregnancy could be used as a marker to predict
      hypertensive complications in women at increased risk. PATIENTS AND METHODS:
      Serum beta2-m concentrations were prospectively measured in 75 pregnant women
      with history of chronic hypertension, chronic renal disease, chronic vascular
      disease or preeclampsia and compared with those in 16 healthy pregnant women.
      RESULTS: Of the 75 women in the study group, 10 (13%) developed preeclampsia and
      20 (26%) had other complications, such as intrauterine growth restriction (n =
      8), fetal or neonatal loss (n = 9) and delivery before 30 weeks of gestation (n =
      8). Gestational age at delivery, birth weight and cesarean section rate were
      significantly worse in the patients with complications than in those without and
      in the healthy controls. No significant difference was detected in early serum
      beta2-m concentrations between the women who later developed preeclampsia or
      other complications and those who did not. There was a significant positive
      correlation of beta2-m concentrations with serum creatinine level (R2 = 0.394, p
      < 0.001), but not with gestational week at blood collection. CONCLUSION: Serum
      beta2-m concentrations are not predictive of the development of preeclampsia or
      other complications in woman at risk.

PMID- 12508963
TI  - The beta2-microglobulin/cystatin C ratio--a potential marker of post-transplant
      lymphoproliferative disease.
AB  - BACKGROUND: As a consequence of more intensified immunosuppression, post
      transplant lymphoproliferative disease (PTLD) is increasingly observed in
      patients after solid-organ transplantation. Beta2-microglobulin, a low-molecular
      weight protein (MW 11.8 kDa), is produced by all nucleated cells as part of the
      HLA complex. Its serum concentration is directly correlated with prognosis in
      patients with lymphatic neoplasms. Like other low-molecular weight proteins,
      beta2-microglobulin is eliminated by glomerular filtration. This complicates its
      use as a tumor marker in renal insufficiency. Cystatin C, a low-molecular weight
      protein of 13.3 kDa, is a new marker of kidney function largely unaffected by
      extrarenal disease. We, therefore, sought to assess the potential of the beta2
      microglobulin/cystatin C ratio (beta2M/Cys) as a marker of lymphoproliferation.
      PATIENTS AND METHODS: Beta2M/Cys was determined by particle-enhanced
      immunonephelometry in sera from 132 children with different degrees of renal
      insufficiency, 5 of whom had lymphoproliferative disease. Renal function was
      assessed using the Schwartz formula. RESULTS: Beta2M/Cys was constant between 1.2
      and 2.4 mg/mg for Schwartz GFR > or = 40 ml/min x 1.73 m2. With lower GFR,
      beta2M/Cys rose progressively, maximum values being found in the hemodialysis
      patients (4.85-11.73). Healthy renal transplant recipients had beta2M/Cys
      comparable to controls. With acute lymphoproliferative disease, all but one
      patient had significantly elevated beta2M/Cys between 2.68 and 3.68 mg/mg, which
      returned to normal in remission (1.67-2.35 mg/mg). The sensitivity of a
      beta2M/Cys ratio > 2.4 mg/mg for the detection of PTLD was 80%, the specificity
      100%, positive predictive value 100%, negative predictive value 90%. CONCLUSION:
      The beta2-microglobulin/cystatin C ratio is a promising parameter of
      lymphoproliferation in patients with normal or mildly impaired renal function.

PMID- 12508964
TI  - Monocyte apoptosis in dialysis patients is Fas ligand-mediated.
AB  - BACKGROUND: The mononuclear phagocyte system plays an important role in host
      defense. Since dialysis patients have been reported to show enhanced leukocytes
      apoptosis, we evaluated the mechanism of increased apoptosis of monocytes in
      dialysis patients. METHODS: Apoptotic studies were carried out on monocytes
      isolated from dialysis patients as well as healthy subjects. The effect of
      dialysis sera and membranes was evaluated on monocyte apoptosis as well as
      monocyte expression of proapoptotic proteins such as Fas and FasL. To confirm the
      role of FasL, we evaluated the effect of activated secretory products on T cell
      apoptosis. In addition, we studied FasL content of dialysis sera and supernatants
      of activated monocytes. RESULTS: Monocytes isolated from dialysis patients (MDP)
      showed a greater magnitude of apoptosis when compared to monocytes isolated from
      healthy subjects (MHS) (MHS, 3.6 +/- 1.1% vs. MDP, 24.3 +/-1.4%). Sera of
      hemodialysis patients (SHD) promoted (p < 0.001) apoptosis of MHS when compared
      to pooled control sera (HPS) (HPS, 0.8 +/- 0.5% vs. SHD, 11.5 +/- 0.5% apoptotic
      cells/field). Dialysis membranes, cellulose acetate membranes in particular,
      promoted monocyte apoptosis. Interestingly, anti-FasL antibodies partly inhibited
      dialysis sera-induced monocyte apoptosis. Dialysis membranes also modulated
      monocyte expression of both Fas and FasL. Secretory products of activated
      monocytes also promoted T cell apoptosis. Dialysis sera and activated monocyte
      secretory products showed increased FasL content. CONCLUSIONS: These results
      suggest that dialysis patients have an increased rate of monocyte apoptosis,
      which is mediated through a uremic milieu (serum factors). One of these serum
      factors seems to be FasL. In addition, dialysis membranes seem to promote
      apoptosis independent of the uremic milieu. The present study provides a
      mechanistical insight into the enhanced apoptosis of monocytes in dialysis
      patients.

PMID- 12508965
TI  - Relationship between body composition, sex hormones and leptinemia in
      hemodialyzed patients with chronic renal failure.
AB  - BACKGROUND: Females are characterized by significantly higher plasma leptin
      concentration than males. It seems likely that sex hormones influence leptinemia
      independently from differences in body composition. The aim of the present study
      was to analyze the contribution of plasma concentrations of testosterone and
      estradiol on leptinemia in hemodialyzed patients. METHODS: 110 hemodialyzed
      patients--HD (60 M, 50 F) and 70 healthy subjects (HS) (30 M, 40 F) were enrolled
      in this study. Plasma leptin, testosterone or estradiol and CRP concentrations
      and body composition by dual-energy X-ray absorptiometry (DEXA) were assessed.
      RESULTS: Total body fat was significantly higher in females than in males (27.5
      +/- 1.5% vs. 17.2 +/- 1.0% of body weight in HD and 36.0 +/- 1.0% vs. 18.2 +/-
      1.4% in HS, respectively). Plasma leptin concentrations were markedly higher in
      females than in males both in HD (27.9 +/- 5.4 ng/ml vs. 9.6 +/- 1.9 ng/ml) and
      HS (16.5 +/- 1.7 ng/ml vs.3.1 +/- 0.4 ng/ml). A highly significant, strong
      positive correlation was found between total fat mass (TFM) and leptinemia in all
      studied groups. No significant univaried correlation between plasma leptin and
      testosterone or estradiol concentrations respectively was found both in HD and
      HS. Multiple regression analyses showed that the main determinant of leptinemia
      is TFM (beta = 0.623 and 0.798 in HS females and males respectively, and beta =
      1.058 and 0.797 in HD females and males respectively). Plasma concentration of
      testosterone (beta = -0.139 and beta = -0.075 in male HD and HS respectively) and
      estradiol (beta = 0.199 and beta = 0.046 in females HD and HS, respectively)
      contributed to leptinemia only in a minor degree. CONCLUSION: Both testosterone
      and estradiol are minor contributors to leptinemia both in HS and HD patients.
      The main determinant of leptinemia in these subjects is total body fat mass.

PMID- 12508966
TI  - Clinical relevance of hemochromatosis-related HFE C282Y/H63D gene mutations in
      patients on chronic dialysis.
AB  - BACKGROUND: The actual prevalence and the clinical relevance of gene mutations of
      HFE (which are linked to hemochromatosis) have not yet been established in
      patients on chronic dialysis. On the basis of theoretical premises, it could be
      hypothesized that these genetic determinants might influence the response to iron
      intake and the susceptibility for iron overload in patients in parenteral iron
      therapy. Furthermore, carriers for these mutations might be prone to develop
      sporadic porphyria cutanea tarda and cardiovascular events. METHODS: C282Y/H63D
      mutations of HFE gene were evaluated in 132 patients (34 in peritoneal dialysis,
      98 in HD) and correlated with biochemical parameters of iron status (ferritin
      (FER) concentration and transferrin saturation (TSAT)), red cell parameters (red
      cell size and hemoglobin content), erythropoietin (EPO) dosage, major
      cardiovascular events and C-reactive protein as marker of chronic inflammation,
      in patients without iron therapy and after i.v. iron supplementation (< or = 60
      mg/week) and with the presence of biopsy-proven porphyria. RESULTS: C282Y
      heterozygous mutation was found in 8/132 (6.6%); H63D homozygous and heterozygous
      mutations were found in 3/132 (2.3%) and 22/132 (16%) patients, respectively. Two
      patients (1.5%) showed double heterozygosis. No differences in baseline serum FER
      and TSAT and the other biochemical and clinical parameters were found in patients
      bearing mutations alleles nor after continuous iron therapy at low dosages.
      However, the prevalence of patients capable of maintaining normal hemoglobin (Hb)
      level without EPO therapy is increased in the C282Y-mutated patients. Only 1
      patient out of the 4 with biopsy-proven porphyria cutanea tarda was bearing gene
      mutations (H63D heterozygosis). CONCLUSION: C282Y/H63D HFE gene mutations do not
      seem to be related to major abnormalities in biochemical parameters of iron
      status in dialysis patients without iron therapy or after i.v. iron
      supplementation, granted that low dosages are employed. Obviously, as our
      patients were exposed to a relatively uniform iron regimen in our clinical center
      (< or = 60 mg/week), it is unclear if other dosing regimens will unmask
      clinically significant differences between the heterozygotes and normals. The
      fact that the C282Y-mutated patients more frequently maintain high Hb values
      without EPO is interesting as could suggest a better use of available iron for
      erythopoiesis, but needs to be confirmed in larger samples. No clear association
      is demonstrated with porphyria cutanea tarda and major cardiovascular events.

PMID- 12508967
TI  - Long-term use of 1.1% amino acid dialysis solution in hypoalbuminemic continuous
      ambulatory peritoneal dialysis patients.
AB  - INTRODUCTION: Malnutrition is a common problem in patients treated with
      continuous ambulatory peritoneal dialysis (CAPD). Hypoalbuminemia in CAPD
      patients is an independent risk factor for death and is associated with
      malnutrition. Previous short-term studies have examined the use of amino acid
      based PD solutions in terms of albumin levels and anthropometric changes, but not
      clinical outcome. We report on the extended use of 1.1% amino acid based
      peritoneal dialysis solution (Nutrineal) and have assessed clinical utility in
      terms of nutrition, biochemical indices, dialysis adequacy and clinical outcomes.
      METHODS: The effect of Nutrineal was studied retrospectively in 22 patients
      during the past 30 months. All patients had an albumin level of < 35 g/l prior to
      commencing Nutrineal, and had either a protein intake < 1.2 g/kg or weight loss
      of > 5% in the previous 3 months. 19 of the 22 patients underwent an 8-week trial
      of oral nutritional supplements with no improvement in serum albumin level.
      Albumin level, normalized protein catabolic rate, weight, Kt/V and creatinine
      clearance were assessed for all patients prior to Nutrineal and at the end of the
      study period. RESULTS: The mean time on Nutrineal therapy was 13.6 months (range
      6-26 months). There were no reported side effects of the treatment. There was an
      average of 1 episode of peritonitis per 23 treatment months, and only 1 patient
      died (4% annually adjusted mortality cf 8.9% on the peritoneal dialysis program
      as a whole). There was a significant increase in albumin level from 22.45 +/-
      0.97 range 14-33 g/l to 25.68 +/- 1.159 range 16-35 g/l (p = 0.0036). Normalized
      protein catabolic rate increased significantly, from 0.898 +/- 0.053 to 1.085 +/-
      0.056 g/kg/day (p = 0.0057). Weight decreased slightly although this did not
      reach statistical significance. Kt/V and creatinine clearance both decreased
      significantly, but remained within the adequate range in > 80% of the patients.
      There was no significant change in residual renal function (mean residual
      creatinine clearance 3.8 +/- 0.59 ml/min at the start of the study period, cf 3.4
      +/- 0.61 ml/min at the end). CONCLUSION: These data suggest that Nutrineal can be
      used safely and effectively for an extended period of time. Such use is
      associated with a low mortality rate and a low peritonitis rate, although
      dialysis adequacy is compromised to a degree.

PMID- 12508968
TI  - Pseudohyperkalemia occurring in a patient with chronic renal failure and
      polycythemia vera without severe leukocytosis or thrombocytosis.
AB  - Pseudohyperkalemia is defined as a serum potassium concentration 0.4 mEq/l
      greater than the plasma concentration. The basis of this phenomenon is the
      release of intracellular potassium from platelets, leukocytes, or erythrocytes,
      commonly in the setting of extreme leukocytosis (> 10 x 10(4)/microl) or
      thrombocytosis (> 60 x 10(4)/microl). We report a case of pseudohyperkalemia in a
      patient with chronic renal failure and polycythemia vera without the finding of
      severe leukocytosis or thrombocytosis (white blood cell count 1.88 x 10(4)/microl
      and platelet count 37.9 x 10(4)/microl, respectively). The serum potassium
      concentration was 8.2 mEq/l, while the plasma potassium level was 6.4 mEq/l in a
      sample obtained simultaneously. The concentrations of platelet factor IV and beta
      thromboglobulin, known to be markers of platelet activation, were greater than
      100 ng/ml and 200 ng/ml, respectively, indicating that platelet activation may
      have been related to the development of pseudohyperkalemia in this patient. These
      findings suggest that pseudohyperkalemia should be considered when hyperkalemia
      is seen in a patient with chronic renal failure and myeloproliferative disorders.

PMID- 12508969
TI  - Acute renal failure and hearing loss due to sodium bromate poisoning: a case
      report and review of the literature.
AB  - Acute renal failure with hearing loss due to sodium bromate intoxication is
      described. A 48-year-old woman who ingested permanent wave neutralizer in a
      suicide attempt and developed anuria was admitted to our hospital for
      hemodialysis. Bromate intoxication was suspected and hemodialysis was carried
      out; she required maintenance dialysis 3 times a week. Irreversible severe
      sensorineural hearing loss continued and peripheral polyneuropathy developed in
      the lower limbs. We measured the concentration of bromine in the serum before and
      after the first hemodialysis and found its removal rate to be 61.3%. This is the
      first report that proved the utility of hemodialysis for bromate intoxication in
      a clinical setting.

PMID- 12508970
TI  - Benign intracranial hypertension in a patient with chronic renal failure,
      precipitated by hemodialysis.

PMID- 12508971
TI  - Effects of candesartan and amlodipine on renal function and electrolytes in renal
      allograft recipients.

PMID- 12508972
TI  - Diving methods and decompression sickness incidence of Miskito Indian underwater
      harvesters.
AB  - Diving conditions, dive profiles, and symptoms of decompression sickness (DCS) in
      a group of Miskito Indian underwater seafood harvesters are described. Dive
      profiles for 5 divers were recorded with dive computers, and DCS symptoms were
      assessed by neurological examination and interview. Divers averaged 10 dives a
      day over a 7-day period with a mean depth of 67 +/- 7 FSW (306 +/- 123 kPa) and
      average in-water time of 20.6 +/- 6.3 minutes. Limb pain was reported on 10
      occasions during 35 man-days of diving. Symptoms were typically managed with
      analgesic medication rather than recompression. Indices of the decompression
      stress were estimated from the recorded profiles using a probabilistic model. We
      conclude that the dives were outside the limits of standard air decompression
      tables and that DCS symptoms were common. The high frequency of limb pain
      suggests the potential for dysbaric bone necrosis for these divers.

PMID- 12508973
TI  - Hyperbaric oxygen therapy in two patients with non-arteritic anterior optic
      neuropathy who did not respond to prednisone.
AB  - Recent advances in understanding the effects of hyperbaric oxygen (HBO) on
      retinal anoxia gave rise to new interest in the possibility of using it as
      therapeutic treatment for ischemic conditions of the retina and optic nerve. Two
      patients with non-arteritic anterior ischemic optic neuropathy due to a high
      grade ophthalmic artery stenosis were treated with HBO at 2 atm abs in an effort
      to increase oxygen delivery for the eye. Both patients showed marked improvements
      of visual acuity and visual field 3-5 months following the event. Our results are
      intriguing although the achieved improvement could be coincidental.

PMID- 12508974
TI  - Wave impedances of drill strings and other periodic media.
AB  - It is commonly known that wave reflections are caused by abrupt spatial
      variations in the physical parameter called wave impedance. When a material
      contains a spatially periodic distribution of wave impedances some very
      interesting and complex wave propagation phenomena will occur. Two examples of
      such periodic structures immediately come to mind: the first is a sandwiched
      structure of two types of plates, say for example, identical layers of thin steel
      plates interspersed with identical thick aluminum plates; and the second is a
      large number of identical long thin pipes that are connected from end to end with
      identical short heavy threaded couplings. The pipe assembly is our primary
      concern here because it represents the drill string, used worldwide to drill for
      natural energy resources. We want to understand how waves propagate through drill
      strings because we want to use them as a means of communication. But while the
      second structure is our primary concern, it is the study of the first structure,
      composed of layers, that is the truly historical problem and the source of much
      of our understanding of this rich set of wave physics. Traditionally, wave
      propagation in periodic media has been studied as an eigenvalue problem. The
      eigenvalues themselves yield information about phase velocities, group
      velocities, passbands, and stopbands. Most often the analysis has stopped there
      and the eigenvectors have been ignored. Here we turn our attention to the
      eigenvectors, using them to evaluate the impedance of the periodic structure with
      particular emphasis on the periodic drill string. As you might expect the
      impedance of the drill string is a complex number, which is evaluated from a very
      complicated expression. However, we have discovered that the impedance at two
      physical locations along the length of each piece of drill pipe in the drill
      string always reduces to a real number. This is immensely important because it
      allows us to match the impedance of the drill string to our communication
      devices. We show how this leads to the effective design of repeaters, noise
      cancelers, wave terminators, and quarter-wave transformers for a drill-string
      communication system.

PMID- 12508975
TI  - A vertical eigenfunction expansion for the propagation of sound in a downward
      refracting atmosphere over a complex impedance plane.
AB  - The propagation of sound in a stratified downward-refracting atmosphere over a
      complex impedance plane is studied. The problem is solved by separating the wave
      equation into vertical and horizontal parts. The vertical part has non-self
      adjoint boundary conditions, so that the well-known expansion in orthonormal
      eigenfunctions cannot be used. Instead, a less widely known eigenfunction
      expansion for non-self-adjoint ordinary differential operators is employed. As in
      the self-adjoint case, this expansion separates the acoustic field into a ducted
      part, expressed as a sum over modes which decrease exponentially with height, and
      an upwardly propagating part, expressed as an integral over modes which are
      asymptotically (with height) plane waves. The eigenvalues associated with the
      modes in this eigenfunction expansion are, in general, complex valued. A
      technique is introduced which expresses the non-self-adjoint problem as a
      perturbation of a self-adjoint one, allowing one to efficiently find the complex
      eigenvalues without having to resort to searches in the complex plane. Finally,
      an application is made to a model for the nighttime boundary layer.

PMID- 12508976
TI  - Complete mode identification for resonance ultrasound spectroscopy.
AB  - This study is devoted to deducing exact elastic constants of an anisotropic solid
      material without using any advance information on the elastic constants by
      incorporating a displacement-distribution measurement into resonant ultrasound
      spectroscopy (RUS). The usual RUS method measures free-vibration resonance
      frequencies of a solid and compares them with calculations to find the most
      suitable set of elastic constants by an inverse calculation. This comparison
      requires mode identification for the measured resonance frequencies, which has
      been difficult and never been free from ambiguity. This study then adopts a laser
      Doppler interferometer to measure the displacement-distribution patterns on a
      surface of the vibrating specimen mounted on pinducers; comparison of the
      measured displacement distributions with those computed permits us to correctly
      identify the measured resonance frequencies, leading to unmistakable
      determination of elastic constants. Because the displacement patterns are hardly
      affected by the elastic constants, an exact answer is surely obtained even when
      unreasonable elastic constants are used as initial guesses at the beginning of
      the inverse calculation. The usefulness of the present technique is demonstrated
      with an aluminum alloy and a langasite crystal.

PMID- 12508977
TI  - Spatial coherence analysis applied to aberration correction using a two
      dimensional array system.
AB  - Complex degree of coherence functions are computed using synthetic and measured
      ultrasound data to demonstrate noteworthy aspects of coherence analysis in the
      context of aberration correction. Coherence functions calculated from synthetic
      data illustrate the importance of proper normalization of the constituent cross
      correlation integrals when weak elements and receiver directivity are significant
      factors. The synthetic data also show that a spike can occur at the zero-lag
      position of the coherence function when the signal-to-noise ratio is reduced by
      element directivity near the edges of a large aperture. The latter observation is
      confirmed by experimental data acquired through tissue-mimicking distributed
      aberration phantoms using a low f-number two-dimensional array system. The
      coherence of data acquired at neighboring elements is not changed by time-shift
      compensation of transmit and receive focusing, but time-shift compensation does
      improve the coherence of echoes measured over larger separations. The resulting
      increase in coherence widths evaluated at levels between 0.2 and 0.5 is
      correlated with narrower -10 dB and -20 dB effective widths in focuses visualized
      using single-transmit images. Iterative focus compensation methods may benefit
      from aberration estimation algorithms that take advantage of these longer-range
      correlations in random-scattering waveforms.

PMID- 12508978
TI  - Modal decomposition method for modeling the interaction of Lamb waves with
      cracks.
AB  - The interaction of the low-order antisymmetric (a0) and symmetric (s0) Lamb waves
      with vertical cracks in aluminum plates is studied. Two types of slots are
      considered: (a) internal crack symmetrical with respect to the middle plane of
      the plate and (b) opening crack. The modal decomposition method is used to
      predict the reflection and transmission coefficients and also the through
      thickness displacement fields on both sides of slots of various heights. The
      model assumes strip plates and cracks, thus considering two-dimensional plane
      strain conditions. However, mode conversion (a0 into s0 and vice versa) that
      occurs for single opening cracks is considered. The energy balance is always
      calculated from the reflection and transmission coefficients, in order to check
      the validity of the results. These coefficients together with the through
      thickness displacement fields are also compared to those predicted using a finite
      element code widely used in the past for modeling Lamb mode diffraction problems.
      Experiments are also made for measuring the reflection and transmission
      coefficients for incident a0 or s0 lamb modes on opening cracks, and compared to
      the numerical predictions.

PMID- 12508979
TI  - On the steady-state and the transient decay methods for the estimation of
      reverberation time.
AB  - The discrepancy between reverberation times of an enclosed sound field measured
      by the steady-state method and by the transient decay method is well-known. So
      far, no clear explanation has been obtained. In this paper, the steady-state
      bandlimited energy in an enclosure and bandlimited power flow into modally
      reactive boundaries are derived to describe the energy balance relationship and
      thus the reverberation time in a frequency band. This reverberation time is then
      compared to that obtained from the transient decay of the sound field based on
      the modal analysis. The comparison provides an understanding of the discrepancy
      mentioned above as well as the physical interpretations of the reverberation
      times estimated by both methods.

PMID- 12508980
TI  - The low-frequency reflection and scattering of the S0 Lamb mode from a circular
      through-thickness hole in a plate: Finite Element, analytical and experimental
      studies.
AB  - A study of the interaction of the S0 Lamb wave with a circular through-thickness
      hole in a plate is presented. The study is limited to the nondispersive frequency
      range of this wave, in which the distributions of stress and displacement are
      simple. This allows a Finite Element analysis to be undertaken using a two
      dimensional membrane discretization. Predictions of the direct reflection of the
      S0 mode and the lateral scattering of the SH0 mode are made for a range of
      diameters of the hole. At the same time, an analytical solution based on modal
      superposition is developed, and this is also used to predict the reflection and
      scattering coefficients. Both sets of predictions are validated by experimental
      measurements. It is found that the trends of the reflection coefficients for
      different hole diameters, frequencies and distances from the hole satisfy a
      simple normalization. On a detailed scale, the functions exhibit undulations
      which are shown to result from the interference of the direct reflection with
      secondary reflections which arrive slightly later.

PMID- 12508981
TI  - Sound transmission across a smooth nonuniform section in an infinitely long duct.
AB  - Sound transmission across a nonuniform section in an infinite duct is studied
      numerically using the finite element method. An impedance matched absorptive
      portion is added to each end of the computational domain so as to avoid the
      undesirable higher mode reflection that will otherwise take place there. Results
      suggest that the sound fields downstream of the nonuniform section inlet are
      complicated and cannot be easily described by the conventional solution of the
      wave equation. The distribution of acoustic energy among the various propagating
      modes well downstream from the outlet of the nonuniform section is also
      discussed. Results show that the first symmetrical higher mode is important for
      all cases. The plane wave becomes important at high frequency with high rate of
      change of the cross-sectional area when the section is a convergent one.

PMID- 12508982
TI  - The low frequency reflection characteristics of the fundamental antisymmetric
      Lamb wave a0 from a rectangular notch in a plate.
AB  - An analysis of the reflection of the fundamental Lamb mode a0 from surface
      breaking rectangular notches in isotropic plates is presented. The results are
      obtained from finite element time domain simulations together with experimental
      measurements. Good agreement is found between the simulations and the
      measurements. Results are shown for a range of notch widths and depths, including
      the special case of a crack, defined as a zero-width notch. The reflection
      coefficient, when plotted as a function of the notch width, exhibits a
      cosinusoidal periodic shape, and this is explained by interference between the
      separate reflections from the start and the end of the notch. The reflection
      coefficient, when plotted as a function of notch depth, shows that in general the
      reflection increases with both frequency and notch depth, but the shapes of the
      functions are complex and there are some surprising features. An analysis of the
      reflection from cracks using the S-parameter scattering approach and some
      simplified descriptions of the crack-opening behavior yields physical
      explanations of the nature of these reflection functions. It is found that
      opening of the crack can be described adequately by a quasistatic assumption only
      when the crack is small, and in other cases a ray theory approach is more
      representative. The reflection function is shown to be a result of contributions
      from both the axial stress and the shear stress in the wave, and the relative
      importance of these varies with the crack depth and the frequency.

PMID- 12508983
TI  - Analysis of piezoelectric strip waveguides based on the effective index and
      pseudospectral element methods.
AB  - Integrated acousto-optical circuits in LiNbO3 are attractive devices for
      applications especially in advanced WDM systems. In order to increase the scale
      of integration and to reduce the RF driving power of these devices, one promising
      approach is to use acoustical waveguides with smaller lateral dimensions. In this
      paper the combination of a pseudospectral elements method (PSEM) and an effective
      index method (EIM) for the analysis of film-loaded surface acoustic waveguides
      (SAWG's) is presented. Numerical results demonstrate the exponential rate of
      convergence of the PSEM and agree with the computations performed via the
      transverse resonance technique. Due to the exponential rate of convergence of the
      PSEM and to a mapping transformation in the substrate, the piezoelectric problem
      in the depth direction of the structures is evaluated by a low number of Legendre
      polynomials. The method is applied to the analysis of several layered SAWG's of
      practical interest for AO devices, such as metal/SiO2/X - YLiNbO3, in which the
      metal is either Au, Al, In, or Ti.

PMID- 12508984
TI  - Tube-wave propagation in a fluid-filled borehole generated by a single point
      force applied to the surrounding formation.
AB  - Propagation of tube waves in an infinite fluid-filled borehole, generated by a
      single-force point source placed in the elastic surrounding formation, is
      analyzed in the long-wave approximation. Integral representations of the precise
      solution are obtained both for fast and slow formations. An asymptotic analysis
      of tube-wave propagation in the fluid-filled borehole is performed on the basis
      of these two integral representations. The complete asymptotic wave field in the
      borehole fluid for a fast formation consists of P and SV phases and the lowest
      eigenmode of the Stoneley wave (tube wave). For a slow formation the conical
      Stoneley wave (Mach wave) is generated. It appears only behind the critical angle
      defined by the ratio of the S wave velocity in the formation to the low-frequency
      Stoneley wave velocity and decays weakly with an offset. Asymptotic wave forms
      are in good agreement with wave forms obtained by straightforward calculations.

PMID- 12508985
TI  - Prediction of sound level at high-frequency bands by means of a simplified
      boundary element method.
AB  - A simplified boundary element method (BEM) for dealing with high-frequency sound
      is proposed. The boundary integral equation is modified into a quadratic form to
      enable the prediction of sound levels in the one-third octave band analysis.
      Monopole and dipole source terms in the conventional BEM are transformed into the
      auto- and cross-spectra of two vibrating sources, in which the cross-spectra are
      eventually neglected by assuming that the correlation coefficients involved are
      negligible. The present method is compared with the Rayleigh integral for
      calculating the sound pressure radiated from a baffled panel, in terms of the
      application limit. The characteristic length of the boundary element and the
      applicable frequency range can be determined by the lower limit value of the
      correlation coefficient. As a test example, the field pressure radiated from a
      partially vibrating sphere is predicted and the resultant trend is in good
      agreement with the analytic solution as far as the related correlation
      coefficient satisfies the assumption. The overdetermination process for
      overcoming nonuniqueness in exterior radiation problems is unnecessary in the
      present method because phase information can be ignored. The results of the
      calculation show that the proposed method is acceptable for solving the exterior
      radiation problem at a high-frequency range in a timely manner.

PMID- 12508986
TI  - Supercritical parametric phase conjugation of ultrasound. Numerical simulation of
      nonlinear and nonstationary mode.
AB  - This paper investigates the saturation mechanism of the nonstationary
      supercritical mode of parametric wave phase conjugation in a magnetostrictive
      medium. The numerical simulation considers the two most probable nonlinear
      mechanisms of interaction between elastic deformation and electromagnetic
      excitation. For the qualitative study of the dynamics of the system, a one
      dimensional numerical simulation is sufficient if applied to an infinite medium
      with a finite active zone. The temporal form of the conjugate wave is obtained
      for both hypotheses. Comparison with experiments shows that only one mechanism
      corresponds to the experimental behavior.

PMID- 12508987
TI  - Strain wave evolution equation for nonlinear propagation in materials with
      mesoscopic mechanical elements.
AB  - Nonlinear wave propagation in materials, where distribution function of
      mesoscopic mechanical elements has very different scales of variation along and
      normally to diagonal of Preisach-Mayergoyz space, is analyzed. An evolution
      equation for strain wave, which takes into account localization of element
      distribution near the diagonal and its slow variation along the diagonal, is
      proposed. The evolution equation provides opportunity to model propagation of
      elastic waves with strain amplitudes comparable to and even higher than
      characteristic scale of element localization near Preisach-Mayergoyz space
      diagonal. Analytical solutions of evolution equation predict nonmonotonous
      dependence of wave absorption on its amplitude in a particular regime. The regime
      of self-induced absorption for small-amplitude nonlinear waves is followed by the
      regime of self-induced transparency for high-amplitude waves. The developed
      theory might be useful in seismology, in high-pressure nonlinear acoustics, and
      in nonlinear acoustic diagnostics of damaged and fatigued materials.

PMID- 12508988
TI  - Traffic noise prediction with the parabolic equation method: validation of a
      split-step Pade approach in complex environments.
AB  - This study deals with sound propagation in typical traffic noise conditions. The
      numerical results are obtained through the split-step Pade method and the
      discrete random Fourier modes technique. These are first evaluated qualitatively,
      by color contour maps showing noise propagation, diffraction by an impedance
      discontinuity or a screen edge, and scattering by atmospheric turbulence. Next,
      our numerical results are quantitatively validated by comparison with analytical
      models and other parabolic equation models. For all the atmospheric conditions
      and geometrical configurations available in literature, the agreement between the
      different methods is very good, except for some cases involving the atmospheric
      turbulence. However, in those particular cases, the split-step Pade results are
      shown to be more consistent with physical theory. Finally, our method seems to be
      very powerful and reliable for traffic noise prediction.

PMID- 12508989
TI  - Computation of scattering from N spheres using multipole reexpansion.
AB  - A computational technique for the solution of problems of wave scattering from
      multiple spheres is developed. This technique, based on the T-matrix method, uses
      the theory for the translation and reexpansion of multipole solutions of the
      Helmholtz equation for fast and exact recursive computation of the matrix
      elements. The spheres can have prescribed radii, impedances, and locations.
      Results are validated by comparison with boundary element calculations, and by
      convergence analyses. The method is much faster than numerical methods based on
      discretization of space, or of the sphere surfaces. An even faster method is
      presented for the case when the spheres are aligned coaxially.

PMID- 12508990
TI  - Time domain investigation of transceiver functions using a known reference
      target.
AB  - During August 1998, a bottom scattering tank experiment was performed at the
      Applied Research Laboratory, University of Texas to measure wideband acoustic
      reverberation from multiple objects (e.g., cobbles and pebbles) placed on a
      sediment simulation of the sea floor. In preparation for processing and analyzing
      the experimental data, time domain scattering measurements made with stainless
      steel and glass balls suspended in the water column were used to calibrate the
      sonar transceiver system by deconvolving the theoretical impulse response for
      steel and glass spheres, obtained via the Faran elastic sphere scattering model,
      from the scattered time signals. It is the analysis of these calibration
      measurements which forms the subject of this paper. Results show the critical
      importance of accurate input-output system calibrations for time domain sound
      scattering research, and successfully demonstrate a time domain method for
      accurately calibrating the complete sonar transceiver function, i.e., both the
      amplitude and time dependence, using a known reference target. The work has
      implications for boundary and volume scattering applications.

PMID- 12508991
TI  - Circumferential-wave phase velocities for empty, fluid-immersed spherical metal
      shells.
AB  - In earlier studies of acoustic scattering resonances and of the dispersive phase
      velocities of surface waves that generate them [see, e.g., Talmant et al., J.
      Acoust. Soc. Am. 86, 278-289 (1989) for spherical aluminum shells] we have
      demonstrated the effectiveness and accuracy of obtaining phase velocity
      dispersion curves from the known acoustic resonance frequencies. This possibility
      is offered through the condition of phase matching after each complete
      circumnavigation of these waves [Uberall et al., J. Acoust. Soc. Am. 61, 711-715
      (1977)], which leads to a very close agreement of resonance results with those
      calculated from three-dimensional elasticity theory whenever the latter are
      available. The present investigation is based on the mentioned resonance
      frequency/elasticity theory connection, and we obtain comparative circumferential
      wave dispersion-curve results for water-loaded, evacuated spherical metal shells
      of aluminum, stainless steel, and tungsten carbide. In particular, the
      characteristic upturn of the dispersion curves of low-order shell-borne
      circumferential waves (A or A0 waves) which takes place on spherical shells when
      the frequency tends towards very low values, is demonstrated here for all cases
      of the metals under consideration.

PMID- 12508992
TI  - Source bearing estimation in the Arctic Ocean using ice-mounted geophones.
AB  - This paper investigates the use of geophones mounted on the surface of Arctic sea
      ice for estimating the bearing to acoustic sources in the water column. The
      approach is based on measuring ice seismic waves for which the direction of
      particle motion is oriented radially outward from the source. However, the
      analysis is complicated by the fact that sea ice supports several types of
      seismic waves, producing complex particle motion that includes significant
      nonradial components. To suppress seismic waves with transverse particle motion,
      seismic polarization filters are applied in conjunction with a straightforward
      rotational analysis (computation of particle-motion power as a function of
      angle). The polarization filters require three-dimensional (3D) measurements of
      particle motion, and apply theoretical phase relationships between vertical and
      horizontal components for the various waves types. In addition, the 180 degrees
      ambiguity inherent in the rotational analysis can be resolved with 3D
      measurements by considering particle motion in the vertical-radial plane. Arctic
      field trials were carried out involving two components. First, a hammer source
      was used to selectively excite the various ice seismic waves to investigate their
      propagation properties and relative importance in bearing estimation. Second,
      impulsive acoustic sources were deployed in the water column at a variety of
      bearings and ranges from 200-1000 m. For frequencies up to 250 Hz, source
      bearings are typically estimated to within an average absolute error of
      approximately 100.

PMID- 12508993
TI  - A numerical optimization approach to acoustic hull array design.
AB  - A numerical optimization approach is presented to optimize passive broadband
      detection performance of hull arrays through the adjustment of array shading
      weights. The approach is developed for general hull arrays in low signal-to-noise
      ratio scenarios, and is shown to converge rapidly to optimal solutions that
      maximize the array's deflection coefficient. The beamformer is not redesigned in
      this approach; only the shading weights of the conventional beamformer are
      adjusted. This approach allows array designers to use the array to minimize the
      impact of known sources of noise on detection at the beamformer output while
      maintaining acoustic array gain against an unknown source. The technique is
      illustrated through numerical examples using hull-borne structural noise as the
      noise source; however, the design concept can be applied to other design
      parameters of the array such as element position, material selection, etc.

PMID- 12508994
TI  - A high frequency amplitude-steered array for real-time volumetric imaging.
AB  - Real-time three-dimensional acoustic imaging is difficult in water or tissue
      because of the slow speed of sound in these media. Conventional pulse-echo data
      collection, which uses at least one transmit pulse per line in the image, does
      not allow for the real-time update of a volume of data at practical ranges.
      Recently, a linear amplitude-steered array was presented that allows the
      collection of a plane of data with a single transmit pulse by spatially
      separating frequencies in the lateral direction. Later, by using a linear array
      with frequency separation in the vertical direction and rotating the array in the
      horizontal direction, volumetric data were collected with a small number of
      transmit pulses. By expanding the linear array to a two-dimensional array, data
      can now be collected for volumetric imaging in real time. In this study, the
      amplitude-steered array at the heart of a real-time volumetric sonar imaging
      system is described, giving the design of the array and describing how data are
      collected and processed to form images. An analysis of lateral resolution in the
      vertical and horizontal directions shows that resolution is improved in the
      direction of frequency separation over systems that use a broad transmit beam.
      Images from simulated data are presented.

PMID- 12508995
TI  - Volumetric imaging with an amplitude-steered array.
AB  - Volumetric acoustic imaging is desirable for the visualization of underwater
      objects and structures; however, the implementation of a volumetric imaging
      system is difficult due to the high channel count of a fully populated two
      dimensional array. Recently, a linear amplitude-steered array with a reduced
      electronics requirement was presented, which is capable of collecting a two
      dimensional set of data with a single transmit pulse. In this study, we
      demonstrate the use of the linear amplitude-steered array and associated image
      formation algorithms for collecting and displaying volumetric data; that is,
      proof of principle of the amplitude-steering concept and the associated image
      formation algorithms is demonstrated. Range and vertical position are obtained by
      taking advantage of the frequency separation of a vertical linear amplitude
      steered array. The third dimension of data is obtained by rotating the array such
      that the mainlobe is mechanically steered in azimuth. Data are collected in a
      water tank at the Pennsylvania State University Applied Research Laboratory for
      two targets: a ladder and three pipes. These data are the first experimental data
      collected with an amplitude-steered array for the purposes of imaging. The array
      is 10 cm in diameter and is operated in the frequency range of 80 to 304 kHz.
      Although the array is small for high-resolution imaging at these frequencies, the
      rungs of the ladder are recognizable in the images. The three pipes are difficult
      to discern in two of the projection images; however, the pipes separated in range
      are clear in the image showing vertical position versus range. The imaging
      concept is demonstrated on measured data, and the simulations agree well with the
      experimental results.

PMID- 12508996
TI  - Laser ultrasonics in copy paper: bending stiffness dependence on temperature and
      moisture content.
AB  - The A0 Lamb mode in copy paper is generated and detected by using laser
      ultrasonics. The frequency dependence of the group velocity of the A0 mode is
      found from the wavelet transform of the measured signal. A best fit of the
      dispersion curve against predictions based on orthotropic plate theory yields an
      estimate of the bending stiffness of the sample. The sample is enclosed in an
      environmental chamber so that the effects of temperature and humidity can be
      controlled. Results indicate that the bending stiffness decreases with increasing
      temperature at an approximate rate of 4 x 10(-6) N m/degrees C, and that it
      decreases with increasing percent moisture content (PMC) at an approximate rate
      of 2 x 10(-5) (N m)/PMC.

PMID- 12508997
TI  - The effect of large openings on cavity amplification at ultrasonic frequencies.
AB  - It is sometimes desired to exploit acoustic amplification in a cavity that is not
      entirely enclosed. Because of the presence of openings in the cavity, acoustic
      energy will leave the cavity and degrade the degree of amplification. The extent
      of this problem is unknown when the size of the openings becomes large relative
      to a wavelength. The present paper describes a quantitative estimation of the
      effect of large openings on the amplification performance of an acoustic cavity.
      Air was assumed to be the working medium. The amplification taking place in a
      rigid-walled rectangular channel excited by a transducer flush-mounted in one
      wall was compared to the amplification that would take place in a bounded
      rectangular resonator excited by the same transducer. It was found, for
      frequencies in the range 25 kHz-1 MHz, that source ka's greater than 37 and 42
      were required in order for the collimation of the transducer beam to overcome the
      leakage of acoustic energy through the openings for one- and two-half wavelength
      resonances, respectively. Experimental measurements conducted over source ka's
      ranging from 6.5 to 26.1, resulted in quality factors 8%-18% lower than
      theoretically predicted values for one-, two-, and three-half wavelength
      resonances.

PMID- 12508998
TI  - Electrode surface profile and the performance of condenser microphones.
AB  - Condenser microphones of all types are traditionally made with a planar electrode
      parallel to an electrically conducting diaphragm, additional diaphragm stiffness
      at acoustic frequencies being provided by the air enclosed in a cavity behind the
      diaphragm. In all designs, the motion of the diaphragm in response to an acoustic
      signal is greatest near its center and reduces to zero at its edges. Analysis
      shows that this construction leads to less than optimal sensitivity and to
      harmonic distortion at high sound levels when the diaphragm motion is appreciable
      compared with its spacing from the electrode. Microphones of this design are also
      subject to acoustic collapse of the diaphragm under the influence of pressure
      pulses such as might be produced by wind. A new design is proposed in which the
      electrode is shaped as a shallow dish, and it is shown that this construction
      increases the sensitivity by about 4.5 dB, and also completely eliminates
      harmonic distortion originating in the cartridge.

PMID- 12508999
TI  - Optimal source distribution for binaural synthesis over loudspeakers.
AB  - When binaural sound signals are presented with loudspeakers, the system inversion
      involved gives rise to a number of problems such as a loss of dynamic range and a
      lack of robustness to small errors and room reflections. The amplification
      required by the system inversion results in loss of dynamic range. The control
      performance of such a system deteriorates severely due to small errors resulting
      from, e.g., misalignment of the system and individual differences in the head
      related transfer functions at certain frequencies. The required large sound
      radiation results in severe reflection which also reduces the control
      performance. A method of overcoming these fundamental problems is proposed in
      this paper. A conceptual monopole transducer is introduced whose position varies
      continuously as frequency varies. This gives a minimum processing requirement of
      the binaural signals for the control to be achieved and all the above problems
      either disappear or are minimized. The inverse filters have flat amplitude
      response and the reproduced sound is not colored even outside the relatively
      large "sweet area." A number of practical solutions are suggested for the
      realization of such optimally distributed transducers. One of them is a
      discretization that enables the use of conventional transducer units.

PMID- 12509000
TI  - Cluster control of a distributed-parameter planar structure--middle authority
      control.
AB  - This paper proposes a generalized active vibration control approach, "cluster
      control," that explicitly targets sets of structural modes with some common
      property. The approach falls into a category of MAC (middle authority control)
      between conventionally used LAC (low authority control) and HAC (high authority
      control), possessing the benefit of stability and control law simplicity
      analogous to LAC, while providing high control performance as well as some
      flexibility of control gain assignment similar to HAC. The structure of a cluster
      control system is outlined, showing that it is possible to control a target
      cluster without affecting the other clusters. A design procedure for the cluster
      control system is then proposed. Experimental results are also presented.

PMID- 12509001
TI  - Analysis of flexural wave velocity and vibration mode in thin cylindrical shell.
AB  - The relationship between the flexural wave velocity and the excited vibration
      mode of a thin cylindrical shell is investigated. The natural frequency
      corresponding to the vibration mode is obtained as the solution of characteristic
      equation of thin cylindrical shell. However, all of these vibration modes are not
      excited actually. To estimate the excited vibration mode, the concept of
      "modified bending stiffness" is introduced, and the influence of each stress
      component upon the modified bending stiffness is analyzed. The excited mode is
      theoretically discriminated from the nonexcited mode based on the smallness of
      this modified bending stiffness. The validity of our theory is confirmed by an
      excellent agreement between theoretical and experimental results on flexural wave
      velocity.

PMID- 12509002
TI  - Sound radiation from a water-filled pipe, radiation into light fluid.
AB  - This paper is concerned with the sound radiation from a water-filled exhaust
      pipe. The pipe opening and a plate attached to it form a vibrating surface for
      this radiation. Fluid-structural coupling between the pipe and enclosed fluid is
      included in the system modeling, but light fluid assumption is used for sound
      radiation into the space above the vibrating surface. In this paper, a numerical
      study on the n = 0 mode in the pipe shows that the wave types associated with
      this mode have different characteristics in two regions of the nondimensional
      frequency omega. In the first region of 0<omega<0.5 and 1<omega<1.3, the fluid
      and structural waves are weakly coupled, and the fluid and structural response of
      the pipe is governed by the resonance of each wave type. The fluid and structural
      waves are strongly coupled in the second region (0.5<omega<1). Simple correlation
      between the pipe response and uncoupled mode distributions does not exist.
      Significant contribution of multiple wave-types to the model energy is evident.
      The ultimate goal of our system modeling is to illustrate the contribution of all
      wave types (structural-borne and water-borne waves of the system) to sound
      radiation from the pipe opening and the attached plate. This paper also
      demonstrates the effect of these waves and their coupling in the water-filled
      pipe and across the plate and pipe boundary on the radiated sound pressure.
      Experimental results obtained in a semi-anechoic room are used to partially
      validate the theoretical and numerical predictions.

PMID- 12509003
TI  - Crack detection by measurement of mechanical impedance of a rotor-bearing system.
AB  - Measurements were done to determine the influence of a transverse crack on the
      mobility of a rotor-bearing system. The results show that the mobility changes
      substantially due to the presence of crack and follows definite trends with the
      crack depth and direction of force application. The significant changes in
      mobility were observed at the natural frequency and at the running frequency of
      the rotor system. Good agreement between the experimental results and numerical
      simulations has been observed. The measurement of mobility has been suggested for
      crack detection and condition monitoring of rotor-bearing systems.

PMID- 12509004
TI  - Three-dimensional vibration analysis of a torus with circular cross section.
AB  - The free vibration characteristics of a torus with a circular cross section are
      studied by using the three-dimensional, small-strain, elasticity theory. A set of
      three-dimensional orthogonal coordinates system, comprising the polar coordinate
      (r, theta) at each circular cross section and the circumferential coordinate phi
      around the ring, is developed. Each of the displacement components u(r),
      v(theta), and w(phi) in the r, theta, and phi directions, respectively, is taken
      as a product of the Chebyshev polynomials in the r direction and the
      trigonometric functions in the theta and phi directions. Eigenfrequencies and
      vibration mode shapes have been obtained via a three-dimensional displacement
      based extremum energy principle. Upper bound convergence of the first seven
      eigenfrequencies accurate to at least six significant figures is obtained by
      using only a few terms of the admissible functions. The eigenfrequency responses
      due to variation of the ratio of the radius of the ring centroidal axis to the
      cross-sectional radius are investigated in detail. Very accurate eigenfrequencies
      and deformed mode shapes of the three-dimensional vibration are presented. All
      major modes such as flexural thickness-shear modes, in-plane stretching modes,
      and torsional modes are included in the analysis. The results may serve as a
      benchmark reference for validating other computational techniques for the
      problem.

PMID- 12509005
TI  - Reduction of sound transmission into a circular cylindrical shell using
      distributed vibration absorbers and Helmholtz resonators.
AB  - A modal expansion method is used to model a cylindrical enclosure excited by an
      external plane wave. A set of distributed vibration absorbers (DVAs) and
      Helmholtz resonators (HRs) are applied to the structure to control the interior
      acoustic levels. Using an impedance matching method, the structure, the acoustic
      cavity, and the noise reduction devices are fully coupled to yield an analytical
      formulation of the structural kinetic energy and acoustic potential energy of a
      treated cylindrical cavity. Lightweight DVAs and small HRs tuned to the natural
      frequencies of the targeted structural and acoustic modes, respectively, result
      in significant acoustic and structural attenuation when the devices are optimally
      damped. Simulations show that significant interior noise reduction can only be
      achieved by adding damping to both structural and acoustic modes, which are
      resonant in the frequency bandwidth of interest. In order to be independent of
      the azimuth angle of the excitation and to avoid unwanted modal interactions, the
      devices are distributed evenly around the cylinder in rings. This treatment can
      only achieve good performance if the structure and the acoustic cavity are
      lightly damped.

PMID- 12509006
TI  - Feasibility of a phased acoustic array for monitoring acoustic signatures from
      meshing gear teeth.
AB  - This paper investigates the feasibility of sensing damage emanating from rotating
      drivetrain elements such as bearings, gear teeth, and drive shafts via airborne
      paths. A planar phased acoustic array is evaluated as a potential fault detection
      scheme for detecting spatially filtered acoustic signatures radiating from
      gearbox components. Specifically, the use of beam focusing and steering to
      monitor individual tooth mesh dynamics is analyzed taking into consideration the
      constraints of the array/gearbox geometry and the spectral content of typical
      gear noise. Experimental results for a linear array are presented to illustrate
      the concepts of adaptive beam steering and spatial acoustic filtering. This
      feasibility study indicates that the planar array can be used to track the
      acoustic signatures at higher harmonics of the gear mesh frequency.

PMID- 12509007
TI  - Temperature dependence of acoustic impedance for specific fluorocarbon liquids.
AB  - Recent studies by our group have demonstrated the efficacy of perfluorocarbon
      liquid nanoparticles for enhancing the reflectivity of tissuelike surfaces to
      which they are bound. The magnitude of this enhancement depends in large part on
      the difference in impedances of the perfluorocarbon, the bound substrate, and the
      propagating medium. The impedance varies directly with temperature because both
      the speed of sound and the mass density of perfluorocarbon liquids are highly
      temperature dependent. However, there are relatively little data in the
      literature pertaining to the temperature dependence of the acoustic impedance of
      these compounds. In this study, the speed of sound and density of seven different
      fluorocarbon liquids were measured at specific temperatures between 20 degrees C
      and 45 degrees C. All of the samples demonstrated negative, linear dependencies
      on temperature for both speed of sound and density and, consequently, for the
      acoustic impedance. The slope of sound speed was greatest for perfluorohexane (
      278 +/- 1.5 cm/s-degrees C) and lowest for perfluorodichlorooctane (-222 +/- 0.9
      cm/s-degrees C). Of the compounds measured, perfluorohexane exhibited the lowest
      acoustic impedance at all temperatures, and perfluorodecalin the highest at all
      temperatures. Computations from a simple transmission-line model used to predict
      reflectivity enhancement from surface-bound nanoparticles are discussed in light
      of these results.

PMID- 12509008
TI  - Sound power flux measurements in strongly exited ducts with flow.
AB  - This contribution describes new robust procedures for the measurement of sound
      power flux at appropriate axial positions along a duct with flow, using pairs of
      flush wall mounted microphones, or pressure transducers. The technology includes
      the application of selective averaging, order tracking, and optimized sampling
      rate methods to identify the small fraction of the total fluctuating wave energy
      that is being propagated along the flow path in a reverberent, or highly reactive
      duct system. Such measurements can also be used to quantify the local acoustic
      characteristics that govern the generation, transfer, and propagation of wave
      energy in the system. Illustrative examples include the determination of the
      acoustic characteristics of individual silencing elements installed in IC engine
      intakes and exhausts both on the flow bench and during controlled acceleration or
      run down on a test bed, where the wave component spectral levels approached 170
      dB.

PMID- 12509009
TI  - Adaptive beamforming for nonstationary arrays.
AB  - Adaptive beamformers automatically adjust to the input data on the sensors in an
      attempt to maximize the bearing resolution of a signal and minimize the effects
      of noise or interfering signals. To the author's knowledge, all adaptive
      beamformers currently available in the literature assume that the sensors are
      stationary over the time required to collect the data. This assumption is invalid
      on arrays of sensors mounted on nonstationary platforms, and results in poor
      beamforming performance. In this paper we present an adaptive beamformer that has
      been designed to operate on nonstationary arrays. The beamformer directly
      incorporates any changes in array shape or heading that may occur during the time
      required to collect the data. The output of the adaptive beamformer is shown for
      both synthetic data and for real data collected on a towed array. Results show
      that signal detection, bearing accuracy, bearing resolution, and interference
      suppression all increase when the array shape and track are incorporated into the
      beamformer if the sensor platform is not stationary.

PMID- 12509010
TI  - Multiple internal reflections in the cochlea and their effect on DPOAE fine
      structure.
AB  - In recent years, evidence has accumulated in support of a two-source model of
      distortion product otoacoustic emissions (DPOAEs). According to such models
      DPOAEs recorded in the ear canal are associated with two separate sources of
      cochlear origin. It is the interference between the contributions from the two
      sources that gives rise to the DPOAE fine structure (a pseudoperiodic change in
      DPOAE level or group delay with frequency). Multiple internal reflections between
      the base of the cochlea (oval window) and the DP tonotopic place can add
      additional significant components for certain stimulus conditions and thus modify
      the DPOAE fine structure. DPOAEs, at frequency increments between 4 and 8 Hz,
      were recorded at fixed f2/f1 ratios of 1.053, 1.065, 1.08, 1.11, 1.14, 1.18,
      1.22, 1.26, 1.30, 1.32, 1.34, and 1.36 from four subjects. The resulting patterns
      of DPOAE amplitude and group delay (the negative of the slope of phase) revealed
      several previously unreported patterns in addition to the commonly reported log
      sine variation with frequency. These observed "exotic" patterns are predicted in
      computational simulations when multiple internal reflections are included. An
      inverse FFT algorithm was used to convert DPOAE data from the frequency to the
      "time" domain. Comparison of data in the time and frequency domains confirmed the
      occurrence of these "exotic" patterns in conjunction with the presence of
      multiple internal reflections. Multiple internal reflections were observed more
      commonly for high primary ratios (f2/f1 > or = 1.3). These results indicate that
      a full interpretation of the DPOAE level and phase (group delay) must include not
      only the two generation sources, but also multiple internal reflections.

PMID- 12509011
TI  - Characterizing cochlear mechano-electric transduction with a nonlinear system
      identification technique: the influence of the middle ear.
AB  - Previously a third-order polynomial equation characterizing mechano-electric
      transduction was obtained from a nonlinear system identification procedure
      applied to an ear canal acoustic signal and cochlear microphonic (CM/AC). In this
      paper, we examine the influence of the linearity and frequency response of the
      intervening middle ear on the nonlinearity, frequency response, and coherence of
      the third-order polynomial model of mechano-electric transduction (MET). Ear
      canal sound pressure (AC), cochlear microphonics (CM), and stapes velocity (SV)
      were simultaneously recorded from Mongolian gerbils. Linear and nonlinear
      transfer and coherence functions relating stapes velocity to the acoustic signal
      (SV/AC), CM to the acoustic signal (CM/AC), and CM to the stapes velocity (CM/SV)
      were computed. The results showed that SV/AC was linear while CM/AC and CM/SV
      were not, indicating that the nonlinearity of CM/AC was not due to nonlinearity
      of the middle ear. The frequency response of the linear term of CM/AC was similar
      to that of ST/AC but differed from that of CM/SV while the cubic term of CM/AC
      was similar to that of CM/SV. This indicates that the frequency dependence of
      CM/AC was due to both the middle ear and frequency dependence of the inner ear.
      Finally the fit of the polynomial model of MET without the middle ear (CM/SV) did
      not improve from the fit including the middle ear (CM/AC). A cochlear model of
      the CM indicated that the lack of improvement was due to the limitations of a
      third-order polynomial equation characterizing the hair cell transducer function.

PMID- 12509012
TI  - Evidence of upward spread of suppression in DPOAE measurements.
AB  - Measurements of DPOAE level in the presence of a suppressor were used to describe
      a pattern that is qualitatively similar to population studies in the auditory
      nerve and to behavioral studies of upward spread of masking. DPOAEs were measured
      in the presence of a suppressor (f3) fixed at either 2.1 or 4.2 kHz, and set to
      each of seven levels (L3) from 20 to 80 dB SPL. In the presence of a fixed f3 and
      L3 combination, f2 was varied from about 1 oct below to at least 1/2 oct above
      f3, while L2 was set to each of 6 values (20-70 dB SPL). L1 was set according to
      the equation L1 = 0.4L2 + 39 [Janssen et al., J. Acoust. Soc. Am. 103, 3418-3430
      (1998)]. At each L2, L1 combination, DPOAE level was measured in a control
      condition in which no suppressor was presented. Data were converted into
      decrements (the amount of suppression, in dB) by subtracting the DPOAE level in
      the presence of each suppressor from the DPOAE level in the corresponding control
      condition. Plots of DPOAE decrements as a function of f2 showed maximum
      suppression when f2 approximately = f3. As L3 increased, the suppressive effect
      spread more towards higher f2 frequencies, with less spread towards lower
      frequencies relative to f3. DPOAE decrement versus L3 functions had steeper
      slopes when f2 > f3, compared to the slopes when f2 < f3. These data are
      consistent with other findings that have shown that response growth for a
      characteristic place (CP) or frequency (CF) depends on the relation between CP or
      CF and driver frequency, with steeper slopes when driver frequency is less than
      CF and shallower slopes when driver frequency is greater than CF. For a fixed
      amount of suppression (3 dB), L3 and L2 varied nearly linearly for conditions in
      which f3 approximately = f2, but grew more rapidly for conditions in which f3 <
      f2, reflecting the basal spread of excitation to the suppressor. The present data
      are similar in form to the results observed in population studies from the
      auditory nerve of lower animals and in behavioral masking studies in humans.

PMID- 12509013
TI  - Spectro-temporal processing in the envelope-frequency domain.
AB  - The frequency selectivity for amplitude modulation applied to tonal carriers and
      the role of beats between modulators in modulation masking were studied. Beats
      between the masker and signal modulation as well as intrinsic envelope
      fluctuations of narrow-band-noise modulators are characterized by fluctuations in
      the "second-order" envelope (referred to as the "venelope" in the following). In
      experiment 1, masked threshold patterns (MTPs), representing signal modulation
      threshold as a function of masker-modulation frequency, were obtained for signal
      modulation frequencies of 4, 16, and 64 Hz in the presence of a narrow-band-noise
      masker modulation, both applied to the same sinusoidal carrier. Carrier
      frequencies of 1.4, 2.8, and 5.5 kHz were used. The shape and relative bandwidth
      of the MTPs were found to be independent of the signal-modulation frequency and
      the carrier frequency. Experiment 2 investigated the extent to which the
      detection of beats between signal and masker modulation is involved in tone-in
      noise (TN), noise-in-tone (NT), and tone-in-tone (TT) modulation masking, whereby
      the TN condition was similar to the one used in the first experiment. A signal
      modulation frequency of 64 Hz, applied to a 2.8-kHz carrier, was tested.
      Thresholds in the NT condition were always lower than in the TN condition,
      analogous to the masking effects known from corresponding experiments in the
      audio-frequency domain. TT masking conditions generally produced the lowest
      thresholds and were strongly influenced by the detection of beats between the
      signal and the masker modulation. In experiment 3, TT masked-threshold patterns
      were obtained in the presence of an additional sinusoidal masker at the beat
      frequency. Signal-modulation frequencies of 32, 64, and 128 Hz, applied to a 2.8
      kHz carrier, were used. It was found that the presence of an additional
      modulation at the beat frequency hampered the subject's ability to detect the
      envelope beats and raised thresholds up to a level comparable to that found in
      the TN condition. The results of the current study suggest that (i) venelope
      fluctuations play a similar role in modulation masking as envelope fluctuations
      do in spectral masking, and (ii) envelope and venelope fluctuations are processed
      by a common mechanism. To interpret the empirical findings, a general model
      structure for the processing of envelope and venelope fluctuations is proposed.

PMID- 12509014
TI  - Psychophysical recovery from pulse-train forward masking in electric hearing.
AB  - Psychophysical pulse-train forward-masking (PTFM) recovery functions were
      measured in fifteen subjects with the Nucleus mini-22 cochlear implant and six
      subjects with the Clarion cochlear implant. Masker and probe stimuli were 500-Hz
      trains of 200- or 77-micros/phase biphasic current pulses. Electrode
      configurations were bipolar for Nucleus subjects and monopolar for Clarion
      subjects. Masker duration was 320 ms. Probe duration was either 10 ms or 30 ms.
      Recovery functions were measured for a high-level masker on a middle electrode in
      all 21 subjects, on apical and basal electrodes in 7 of the Nucleus and 3 of the
      Clarion subjects, and for multiple masker levels on the middle electrode in 8
      Nucleus subjects and 6 Clarion subjects. Recovery functions were described by an
      exponential process in which threshold shift (in microA) decreased exponentially
      with increasing time delay between the offset of the masker pulse train and the
      offset of the probe pulse train. All but 3 of the 21 subjects demonstrated
      recovery time constants on a middle electrode that were less than 95 ms. The mean
      time constant for these 18 subjects was 54 ms (s.d. 17 ms). Three other subjects
      tested on three electrodes exhibited time constants larger than 95 ms from an
      apical electrode only. Growth-of-masking slopes depended upon time delay, as
      expected from an exponential recovery process, i.e., progressively shallower
      slopes were observed at time delays of 10 ms and 50 ms. Recovery of threshold
      shift (in microA) for PTFM in electrical hearing behaves inthe same way as
      recovery of threshold shift (in dB) for pure-tone forward masking in acoustic
      hearing. This supports the concept that linear microamps are the electrical
      equivalent of acoustic decibels. Recovery from PTFM was not related to speech
      recognition in a simple manner. Three subjects with prolonged PTFM recovery
      demonstrated poor speech scores. The remaining subjects with apparently normal
      PTFM recovery demonstrated speech scores ranging from poor to excellent. Findings
      suggest that normal PTFM recovery is only one of several factors associated with
      good speech recognition in cochlear-implant listeners. Comparisons of recovery
      curves for 10- and 30-ms probe durations in two subjects showed little or no
      temporal integration at time delays less than 95 ms where recovery functions have
      steep slopes. The same subjects exhibited large amounts of temporal integration
      at longer time delays where recovery slopes are more gradual. This suggests that
      probe detection depends primarily on detection of the final pulses in the probe
      stimulus and supports the use of offset-to-offset time delays for characterizing
      PTFM recovery in electric hearing.

PMID- 12509015
TI  - Susceptibility to acoustic trauma in young and aged gerbils.
AB  - The effect of age on susceptibility to noise-induced hearing loss (NIHL), the
      effect of gender on the interaction of age-related hearing loss (ARHL) and NIHL,
      and the relative contributions of ARHL and NIHL to total hearing loss are poorly
      understood. The issues are difficult to resolve empirically in human subjects
      because of lack of control over extrinsic variables and for ethical reasons.
      Accordingly, these issues were examined in a well-studied animal model of both
      ARHL and NIHL, the Mongolian gerbil. Animals were exposed to an intense tone (3.5
      kHz, 113 dB SPL, 1 h) either as young adults (6-8 months) or near the end of the
      average lifespan of the species (34-38 months). Hearing thresholds were
      determined with the auditory brainstem response (ABR). ARHL was approximately 5
      10 dB, with slightly more observed in males at 16 kHz (p<0.05). NIHL of
      approximately 15-20 dB was similar for the young and old groups, suggesting no
      differences in susceptibility as a function of age. There were no gender
      differences in NIHL. The relative contributions of ARHL and NIHL to total hearing
      loss in aged, noise-exposed gerbils were predicted by an addition of ARHL and
      NIHL in dB, similar to an international standard on hearing loss allocation, ISO
      1999 [Determination of Occupational Noise Exposure and Estimation of Noise
      Induced Hearing Impairment (1990)]. Previous evaluations of ISO-1999 using the
      gerbil animal model concluded that addition of ARHL and NIHL in dB overpredicts
      total hearing loss. However, in these studies, ARHL was large and nearly equal to
      NIHL. In the current study, where ARHL was much less than NIHL, addition of the
      two factors in dB, as recommended by ISO-1999, results in fairly accurate
      predictions of total hearing loss.

PMID- 12509016
TI  - Virtual pitch integration for asynchronous harmonics.
AB  - This experiment examined the generation of virtual pitch for harmonically related
      tones that do not overlap in time. The interval between successive tones was
      systematically varied in order to gauge the integration period for virtual pitch.
      A pitch discrimination task was employed, and both harmonic and nonharmonic tone
      series were tested. The results confirmed that a virtual pitch can be generated
      by a series of brief, harmonically related tones that are separated in time.
      Robust virtual pitch information can be derived for intervals between successive
      40-ms tones of up to about 45 ms, consistent with a minimum estimate of
      integration period of about 210 ms. Beyond intertone intervals of 45 ms,
      performance becomes more variable and approaches an upper limit where
      discrimination of tone sequences can be undertaken on the basis of the individual
      frequency components. The individual differences observed in this experiment
      suggest that the ability to derive a salient virtual pitch varies across
      listeners.

PMID- 12509017
TI  - Auditory processing efficiency deficits in children with developmental language
      impairments.
AB  - The "temporal processing hypothesis" suggests that individuals with specific
      language impairments (SLIs) and dyslexia have severe deficits in processing
      rapidly presented or brief sensory information, both within the auditory and
      visual domains. This hypothesis has been supported through evidence that language
      impaired individuals have excess auditory backward masking. This paper presents
      an analysis of masking results from several studies in terms of a model of
      temporal resolution. Results from this modeling suggest that the masking results
      can be better explained by an "auditory efficiency" hypothesis. If impaired or
      immature listeners have a normal temporal window, but require a higher signal-to
      noise level (poor processing efficiency), this hypothesis predicts the observed
      small deficits in the simultaneous masking task, and the much larger deficits in
      backward and forward masking tasks amongst those listeners. The difference in
      performance on these masking tasks is predictable from the compressive
      nonlinearity of the basilar membrane. The model also correctly predicts that
      backward masking (i) is more prone to training effects, (ii) has greater inter-
      and intrasubject variability, and (iii) increases less with masker level than do
      other masking tasks. These findings provide a new perspective on the mechanisms
      underlying communication disorders and auditory masking.

PMID- 12509018
TI  - Humans detect gaps in broadband noise according to effective gap duration without
      additional cues from abrupt envelope changes.
AB  - Previous studies of behavior and IC single units in the mouse support theoretical
      expectations that gaps with ramped trailing markers have reduced detectability
      compared to equivalent gaps with ramped leading markers. In experiment 1,
      detection probability and response speeds of humans listening for gaps in
      broadband noise were investigated by independently varying either leading marker
      fall-time (FT) or trailing marker rise-time (RT). Gaps with silent duration of 1,
      4, or 12 ms were presented 2 s into a 3-s noise burst, with either abrupt marker
      onsets and offsets or linearly ramped RT/FT of 2, 4, or 8 ms durations. Addition
      of a nonzero RT or FT to the gap silent period increased detectability and also
      increased reaction speed on trials with "Yes" response, but there was no
      difference in detectability or response speeds between RT and FT conditions.
      Experiment 2 extended this finding to gaps having two, one, or no abrupt marker
      edges. These findings suggest that human listeners do not make use of abrupt
      onset or offset information to enhance gap detection, but seem to rely on the
      effective sound level reduction associated with the gap for detection.

PMID- 12509019
TI  - Effect of modulator asynchrony of sinusoidal and noise modulators on frequency
      and amplitude modulation detection interference.
AB  - The effect on modulation detection interference (MDI) of timing of gating of the
      modulation of target and interferer, with synchronously gated carriers, was
      investigated in three experiments. In a two-interval, two-alternative forced
      choice adaptive procedure, listeners had to detect 15 Hz sinusoidal amplitude
      modulation (AM) or frequency modulation (FM) imposed for 200 ms in the temporal
      center of a 600 ms target sinusoidal carrier. In the first experiment, 15 Hz
      sinusoidal FM was imposed in phase on both target and interferer carriers.
      Thresholds were lower for nonoverlapping than for synchronous modulation of
      target and interferer, but MDI still occurred for the former. Thresholds were
      significantly higher when the modulators were gated synchronously than when the
      interferer modulator was gated on before and off after that of the target. This
      contrasts with the findings of Oxenham and Dau [J. Acoust. Soc. Am. 110, 402-408
      (2001)], who reported no effect of modulation asynchrony on AM detection
      thresholds, using a narrowband noise modulator. Using FM, experiment 2 showed
      that for temporally overlapping modulation of target and interferer, modulator
      asynchrony had no significant effect when the interferer was modulated by a
      narrowband noise. Experiment 3 showed that, for AM, synchronous gating of
      modulation of the target and interferer produced lower thresholds than
      asynchronous gating, especially for sinusoidal modulation of the interferer.
      Results are discussed in terms of specific cues available for periodic
      modulation, and differences between perceptual grouping on the basis of common AM
      and FM.

PMID- 12509020
TI  - Within-ear and across-ear interference in a cocktail-party listening task.
AB  - Although many researchers have shown that listeners are able to selectively
      attend to a target speech signal when a masking talker is present in the same ear
      as the target speech or when a masking talker is present in a different ear than
      the target speech, little is known about selective auditory attention in tasks
      with a target talker in one ear and independent masking talkers in both ears at
      the same time. In this series of experiments, listeners were asked to respond to
      a target speech signal spoken by one of two competing talkers in their right
      (target) ear while ignoring a simultaneous masking sound in their left
      (unattended) ear. When the masking sound in the unattended ear was noise,
      listeners were able to segregate the competing talkers in the target ear nearly
      as well as they could with no sound in the unattended ear. When the masking sound
      in the unattended ear was speech, however, speech segregation in the target ear
      was substantially worse than with no sound in the unattended ear. When the
      masking sound in the unattended ear was time-reversed speech, speech segregation
      was degraded only when the target speech was presented at a lower level than the
      masking speech in the target ear. These results show that within-ear and across
      ear speech segregation are closely related processes that cannot be performed
      simultaneously when the interfering sound in the unattended ear is qualitatively
      similar to speech.

PMID- 12509021
TI  - Pressure and velocity profiles in a static mechanical hemilarynx model.
AB  - This study examined pressure and velocity profiles in a hemilarynx mechanical
      model of phonation. The glottal section had parallel walls and was fabricated
      from hard plastic. Twelve pressure taps were created in the vocal fold surface
      and connected to a differential pressure transducer through a pressure switch.
      The glottal gap was measured with feeler gauges and the uniform glottal duct was
      verified by use of a laser system. Eight pressure transducers were placed in the
      flat wall opposite the vocal fold. Hot-wire anemometry was used to obtain
      velocity profiles upstream and downstream of the glottis. The results indicate
      that the pressure distribution on the vocal fold surface was consistent with
      pressure change along a parallel duct, whereas the pressures on the opposite flat
      wall typically were lower (by 8%-40% of the transglottal pressure just past mid
      glottis). The upstream velocity profiles were symmetric regardless of the
      constriction shape and size. The jet flow downstream of the glottis was turbulent
      even for laminar upstream conditions. The front of the jet was consistently
      approximately 1.5 mm from the flat wall for glottal gaps of 0.4, 0.8 and 1.2 mm.
      The turbulence intensity also remained approximately at the same location of
      about 4 mm from the flat wall for the two larger gaps.

PMID- 12509022
TI  - Quantifying the intelligibility of speech in noise for non-native talkers.
AB  - The intelligibility of speech pronounced by non-native talkers is generally lower
      than speech pronounced by native talkers, especially under adverse conditions,
      such as high levels of background noise. The effect of foreign accent on speech
      intelligibility was investigated quantitatively through a series of experiments
      involving voices of 15 talkers, differing in language background, age of second
      language (L2) acquisition and experience with the target language (Dutch).
      Overall speech intelligibility of L2 talkers in noise is predicted with a
      reasonable accuracy from accent ratings by native listeners, as well as from the
      self-ratings for proficiency of L2 talkers. For non-native speech, unlike native
      speech, the intelligibility of short messages (sentences) cannot be fully
      predicted by phoneme-based intelligibility tests. Although incorrect recognition
      of specific phonemes certainly occurs as a result of foreign accent, the effect
      of reduced phoneme recognition on the intelligibility of sentences may range from
      severe to virtually absent, depending on (for instance) the speech-to-noise
      ratio. Objective acoustic-phonetic analyses of accented speech were also carried
      out, but satisfactory overall predictions of speech intelligibility could not be
      obtained with relatively simple acoustic-phonetic measures.

PMID- 12509023
TI  - Direct magnitude estimation and interval scaling of pleasantness and severity in
      dysphonic and normal speakers.
AB  - The purpose of this study was to determine the validity of voice pleasantness and
      overall voice severity ratings of dysphonic and normal speakers using direct
      magnitude estimation (DME) and equal-appearing interval (EAI) auditory-perceptual
      scaling procedures. Twelve naive listeners perceptually evaluated voice
      pleasantness and severity from connected speech samples produced by 24 adult
      dysphonic speakers and 6 normal adult speakers. A statistical comparison of the
      two auditory-perceptual scales yielded a linear relationship representative of a
      metathetic continuum for voice pleasantness. A statistical relationship that is
      consistent with a prothetic continuum was revealed for ratings of voice severity.
      These data provide support for the use of either DME or EAI scales when making
      auditory-perceptual judgments of pleasantness, but only DME scales when judging
      overall voice severity for dysphonic speakers. These results suggest further
      psychophysical study of perceptual dimensions of voice and speech must be
      undertaken in order to avoid the inappropriate and invalid use of EAI scales used
      in the auditory-perceptual evaluation of the normal and dysphonic voice.

PMID- 12509024
TI  - The effects of familiarization on intelligibility and lexical segmentation in
      hypokinetic and ataxic dysarthria.
AB  - This study is the third in a series that has explored the source of
      intelligibility decrement in dysarthria by jointly considering signal
      characteristics and the cognitive-perceptual processes employed by listeners. A
      paradigm of lexical boundary error analysis was used to examine this interface by
      manipulating listener constraints with a brief familiarization procedure. If
      familiarization allows listeners to extract relevant segmental and suprasegmental
      information from dysarthric speech, they should obtain higher intelligibility
      scores than nonfamiliarized listeners, and their lexical boundary error patterns
      should approximate those obtained in misperceptions of normal speech. Listeners
      transcribed phrases produced by speakers with either hypokinetic or ataxic
      dysarthria after being familiarized with other phrases produced by these
      speakers. Data were compared to those of nonfamiliarized listeners [Liss et al.,
      J. Acoust. Soc. Am. 107, 3415-3424 (2000)]. The familiarized groups obtained
      higher intelligibility scores than nonfamiliarized groups, and the effects were
      greater when the dysarthria type of the familiarization procedure matched the
      dysarthria type of the transcription task. Remarkably, no differences in lexical
      boundary error patterns were discovered between the familiarized and
      nonfamiliarized groups. Transcribers of the ataxic speech appeared to have
      difficulty distinguishing strong and weak syllables in spite of the
      familiarization. Results suggest that intelligibility decrements arise from the
      perceptual challenges posed by the degraded segmental and suprasegmental aspects
      of the signal, but that this type of familiarization process may differentially
      facilitate mapping segmental information onto existing phonological categories.

PMID- 12509025
TI  - An alternative to the traveling-wave approach for use in two-port descriptions of
      acoustic bores.
AB  - For more than a decade, the digital waveguide model for musical instruments has
      been improved through the simulation of cylindrical and conical bores. But
      several difficulties remain, such as instabilities due to growing exponentials
      which appear when two conical bores are connected with decreasing taper. In this
      paper, an alternative overcoming these difficulties is proposed and can be
      extended to shapes other than cylinders, cones, and hyperbolic horns. A two-port
      model with more general state variables than usual traveling waves works
      efficiently for any shape without discontinuities in cross section. The equations
      for connecting separate elements at discontinuities make this two-port model
      appropriate for use in time domain simulation of the physical behavior of the
      wind instrument and its interactions with the player. The potential of this new
      approach is illustrated by several detailed examples.

PMID- 12509026
TI  - Short sound decay of ancient Chinese music bells.
AB  - Ancient Chinese music bells, which have oval-like cross sections, possess the
      unique feature of a short sound-decay time that is especially suitable for music
      with fast tempo. Although recorded in the literature nearly 1000 years ago, this
      feature has never been truly understood. Recent damping measurement of oval pipes
      with different axial ratios suggested a challenging task for acousticians as the
      increase of the modal damping with the pipe's axial ratio is significant only
      when the pipe response is measured in air but not in vacuum. In this paper, the
      decrease of sound-decay time of oval pipes with the increased cross-section
      ovality is investigated. This is the first time that such short sound-decay
      feature is explained in terms of the rich sound radiation characteristics of the
      symmetric modes of music bells and the oval pipes. Finite element and boundary
      element methods are employed to explain how axial ratio significantly affects the
      normal velocity distribution, radiation efficiency, and directivity of acoustic
      modes.

PMID- 12509027
TI  - Probability density functions for hyperbolic and isodiachronic locations.
AB  - Animal locations are sometimes estimated with hyperbolic techniques by estimating
      the difference in distances of their sounds between pairs of receivers. Each pair
      specifies the animal's location to a hyperboloid because the speed of sound is
      assumed to be spatially homogeneous. Sufficient numbers of intersecting
      hyperboloids specify the location. A nonlinear method is developed for computing
      probability density functions for location. The method incorporates a priori
      probability density functions for the receiver locations, the speed of sound,
      winds, and the errors in the differences in travel time. The traditional linear
      approximation method overestimates bounds for probability density functions by
      one or two orders of magnitude compared with the more accurate nonlinear method.
      The nonlinear method incorporates a generalization of hyperbolic methods because
      the average speed of sound is allowed to vary between different receivers and the
      source. The resulting "isodiachronic" surface is the locus of points on which the
      difference in travel time is constant. Isodiachronic locations yield correct
      location errors in situations where hyperbolic methods yield incorrect results,
      particularly when the speed of propagation varies significantly between a source
      and different receivers.

PMID- 12509028
TI  - Method of improved scatterer size estimation and application to parametric
      imaging using ultrasound.
AB  - The frequency dependence of RF signals backscattered from random media (tissues)
      has been used to describe the microstructure of the media. The frequency
      dependence of the backscattered RF signal is seen in the power spectrum.
      Estimates of scatterer properties (average scatterer size) from an interrogated
      medium are made by minimizing the average squared deviation (MASD) between the
      measured power spectrum and a theoretical power spectrum over an analysis
      bandwidth. Estimates of the scatterer properties become increasingly inaccurate
      as the average signal to noise ratio (SNR) over the analysis bandwidth becomes
      smaller. Some frequency components in the analysis bandwidth of the measured
      power spectrum will have smaller SNR than other frequency components. The
      accuracy of estimates can be improved by weighting the frequency components that
      have the smallest SNR less than the frequencies with the largest SNR in the MASD.
      A weighting function is devised that minimizes the noise effects on the estimates
      of the average scatterer sizes. Simulations and phantom experiments are conducted
      that show the weighting function gives improved estimates in an attenuating
      medium. The weighting function is applied to parametric images using scatterer
      size estimates of a rat that had developed a spontaneous mammary tumor.

PMID- 12509029
TI  - The whistles of Hawaiian spinner dolphins.
AB  - The characteristics of the whistles of Hawaiian spinner dolphins (Stenella
      longirostris) are considered by examining concurrently the whistle repertoire
      (whistle types) and the frequency of occurrence of each whistle type (whistle
      usage). Whistles were recorded off six islands in the Hawaiian Archipelago. In
      this study Hawaiian spinner dolphins emitted frequency modulated whistles that
      often sweep up in frequency (47% of the whistles were upsweeps). The frequency
      span of the fundamental component was mainly between 2 and 22 kHz (about 94% of
      the whistles) with an average mid-frequency of 12.9 kHz. The duration of spinner
      whistles was relatively short, mainly within a span of 0.05 to 1.28 s (about 94%
      of the whistles) with an average value of 0.49 s. The average maximum frequency
      of 15.9 kHz obtained by this study is consistent with the body length versus
      maximum frequency relationship obtained by Wang et al. (1995a) when using spinner
      dolphin adult body length measurements. When comparing the average values of
      whistle parameters obtained by this and other studies in the Island of Hawaii,
      statistically significant differences were found between studies. The reasons for
      these differences are not obvious. Some possibilities include differences in the
      upper frequency limit of the recording systems, different spinner groups being
      recorded, and observer differences in viewing spectrograms. Standardization in
      recording and analysis procedure is clearly needed.

PMID- 12509030
TI  - Empirical refinements applicable to the recording of fish sounds in small tanks.
AB  - Many underwater bioacoustical recording experiments (e.g., fish sound production
      during courtship or agonistic encounters) are usually conducted in a controlled
      laboratory environment of small-sized tanks. The effects of reverberation,
      resonance, and tank size on the characteristics of sound recorded inside small
      tanks have never been fully addressed, although these factors are known to
      influence the recordings. In this work, 5-cycle tone bursts of 1-kHz sound were
      used as a test signal to investigate the sound recorded in a 170-l rectangular
      glass tank at various depths and distances from a transducer. The dominant
      frequency, sound-pressure level, and power spectrum recorded in small tanks were
      significantly distorted compared to the original tone bursts. Due to resonance,
      the dominant frequency varied with water depth, and power spectrum level of the
      projected frequency decreased exponentially with increased distance between the
      hydrophone and the sound source; however, the resonant component was nearly
      uniform throughout the tank. Based on the empirical findings and theoretical
      calculation, a working protocol is presented that minimizes distortion in fish
      sound recordings in small tanks. To validate this approach, sounds produced by
      the croaking gourami (Trichopsis vittata) during staged agonistic encounters were
      recorded according to the proposed protocol in an 1800-l circular tank and in a
      37-l rectangular tank to compare differences in acoustic characteristics
      associated with tank size and recording position. The findings underscore
      pitfalls associated with recording fish sounds in small tanks. Herein, an
      empirical solution to correct these distortions is provided.

PMID- 12509031
TI  - Antimasking aspects of harp seal (Pagophilus groenlandicus) underwater
      vocalizations.
AB  - Underwater sounds are very important in social communication of harp seals
      (Pagophilus groenlandicus) because they are the main means of long- and short
      distance communication. Individual harp seals must try to avoid being masked and
      emit only those calls that will benefit them. Underwater vocalizations of harp
      seals were recorded during the breeding season. The physical characteristics
      associated with antimasking attributes of 16 call types were examined. Rising
      frequency or increasing amplitude within calls were not common. Most of the calls
      ended abruptly (range 145-966 dB/s), but call onset was more gradual. At high
      calling rates (95.1-135 calls/min) there were significantly more calls
      overlapping temporally than at medium (75.1-95 calls/min) or low (35-75
      calls/min) calling rates, but even at the highest calling rates, 79.1% of the
      calls were not overlapped. When 2, 3, or 4 calls overlapped, there were
      significantly fewer frequency separations of less than 1/3 octave than would be
      expected by chance. This is important because sounds that are separated by less
      than 1/3 octave likely mask each other. When 2-4 calls are occurring
      simultaneously, only 4.5% to 14.2% are masked by virtue of being within 1/3
      octave from their nearest neighbor. None of the overlappping calls was of the
      same type. This suggests that the seals are actively listening to each other's
      calls and are not randomly using the different call types. Harp seals use
      frequency and temporal separation in conjunction with a wide vocal repertoire to
      avoid masking each other.

PMID- 12509032
TI  - In harm's way: children's environmental health.
AB  - 2002 has been a landmark year for children's environmental health, with several
      major international conferences dedicated to the issue and the publication of
      numerous reports and studies. In this article we review how and why children's
      health has emerged as a key environmental policy issue and what the analytical
      sciences can contribute.

PMID- 12509033
TI  - Focus on education and training project planning and management exercise (PPME)-
      an approach to practical study in environmental chemistry.

PMID- 12509034
TI  - Monitoring volatile organic compounds in air--the development of ISO standards
      and a critical appraisal of the methods.

PMID- 12509035
TI  - Fluoride in fractionated soil samples of Ajmer district, Rajasthan.
AB  - The natural abundance of fluoride in soils of the Ajmer distict, Rajasthan was
      examined. From undisturbed soil, the top 15 cm of the profile was examined and
      the soil split into fractions based on sand, silt and clay particle size. Clay
      contained a high amount of fluoride, whereas sand and silts are enriched with
      much less fluoride. The relation between the soil fractions in observed clay
      fraction fluoride content matched groundwater fluoride variation. However, the
      enrichment of fluoride material extracted from the largest soil fraction had
      considerably lower amounts of clay relative to that from the smaller fractions.

PMID- 12509036
TI  - Chemical sequential extraction for metal partitioning in environmental solid
      samples.
AB  - A comprehensive review of the sequential extraction schemes for metal
      fractionation in environmental samples (ie., sediment, soil, sewage sludge, fly
      ash, etc.) is presented. The review contains more than 400 references and covers
      principally the literature published over the last decade. The use of each
      reagent involved in these schemes is looked at critically, and guidelines for
      their selectivity and extraction capacity are given. The operational character of
      these schemes is emphasised. Topics such as comparability between sequential
      extraction schemes of widespread use, harmonisation, acceleration, validation,
      etc. are addressed and future developments outlined.

PMID- 12509037
TI  - Sampling procedure for the foliar analysis of deciduous trees.
AB  - Sampling can be the source of the greatest errors in the overall results of
      foliar analysis. This paper reviews the variability in heavy metal concentrations
      in tree crowns, which is a feature that should be known and understood when
      designing a suitable leaf sampling procedure. The leaf sampling procedures
      applied in 75 articles were examined. Most of the environmental studies used a
      closely related form of the UN/ECE-EC leaf sampling procedure, which was
      developed for the long-term monitoring of forest condition. Studies with
      objectives outside the UN/ECE-EC field of application should utilize a sampling
      procedure that is in accordance with the objectives of the study and based on the
      observed variation in pilot and similar studies. The inherent sources of heavy
      metal variability inside the stand, i.e. the crown class, stand management, site
      properties, crown dimensions, infections, seasons, etc. were discussed, but the
      underlying causes of this variability are rarely understood. The inherent
      variability in tree crowns is the reason for using leaf sampling as a tool in
      pollution studies. The objectives of a pollution study determine which sources of
      variability are utilized by the researcher.

PMID- 12509038
TI  - Determining the agricultural ammonia immission using bark bio-monitoring:
      comparison with passive sampler measurements.
AB  - Bark samples of spruce, pine and oak trees were collected at two sites in
      southern Bavaria which are characterized by high agricultural ammonia emissions.
      The samples were taken using a recently developed bark sampling device which
      removes a defined layer of the bark. The bark was then analysed for ammonium
      concentration in order to reflect the environmental ammonia immission. The
      measured bark concentrations decreased with rising distance between the sample
      trees and the ammonia source. This applied (i) to measurements inside a closed
      forest stand ranging from forest edge with high immission to forest interior with
      much lower immission, and (ii) to the open field where single-standing trees were
      sampled. Comparing the ammonium concentrations among the three different tree
      species revealed significant correlations. Thus, it could be shown that old
      spruce trees are as usable for bark bio-monitoring as the traditionally used pine
      and oak trees. The ammonium concentrations of the bark were significantly
      correlated to measurements taken by ammonia passive samplers at the same
      locations. These results indicate that bark samples may be used for a
      standardised monitoring of airborne ammonia load. A major advantage of the
      technique is the determination of the long-term accumulative ammonia load using a
      single measurement.

PMID- 12509039
TI  - Diffusive uptake in passive and active adsorbent sampling using thermal
      desorption tubes.
AB  - Low flow active sampling techniques collecting vapors and gases using thermally
      desorbable adsorbents are now feasible and desirable in many applications as they
      permit long integration times, the potential for miniaturized sampling
      configurations, and other advantages. At very low air flow rates (< 1 ml min(
      1)), diffusive uptake on adsorbents in conventional sorbent tubes may equal or
      exceed the active (pumped) uptake rate, and even at low flow rates (1-4 ml min(
      1)), diffusive uptake may significantly bias measurements. Thus, corrections to
      account for the diffusive flux or means to limit the diffusive uptake are needed
      in low flow applications. This paper presents (1) a theoretical analysis of the
      role of diffusive and advective uptake for several sampling geometries of tube
      type samplers; (2) experimental confirmation using both laboratory and field
      studies; (3) estimates of the tortuosity and porosity of the glass wool packing
      used to retain the adsorbent, parameters needed to estimate diffusive fluxes in
      passive and active sampling; (4) a demonstration that orifice-equipped low flow
      active samplers can reduce diffusive uptake and improve precision, and (5) a
      model predicting the saturated adsorbent layer that helps to account for the
      gradual decline in uptake rates seen in passive sampling. Diffusive uptake will
      depend on the tube configuration and diffusion coefficient of the substance of
      interest, but for conventional sampling tubes (0.4-0.5 cm id, 1.5 cm air gap),
      sample flow rates should be maintained above 1 to 4 ml min(-1) to keep errors
      below 5%. Laboratory experiments showed close agreement with theoretical
      calculations, and the field study using 1 to 4 d sampling periods and 0.3 ml min(
      1) flows demonstrated that the orifice-equipped samplers essentially eliminated
      diffusive uptake. No significant practical difficulties are encountered using
      orifices, e.g., pressure drop is minimal. Experimental estimates of tortuosity
      (0.79 +/- 0.02) and porosity (0.92 +/- 0.10) of the glass wool packing (0.3 cm
      length) represent relatively little resistance to diffusion; however, variation
      in the packing and adsorbent placement can degrade the precision achievable by
      passive samplers. Diffusion barriers, consisting most simply of an orifice, may
      be used to lower the diffusive uptake. A needle-type orifice permits flows below
      0.1 ml min(-1) and is suitable for sampling periods as long as several weeks, and
      it provided greater precision than conventional open-ended sampling tubes (8%
      compared to 13%). Finally, the gradual decrease in diffusive fluxes often seen in
      passive sampling is attributed to additional resistance posed by a saturated
      adsorbent layer, in agreement with a simple model based on total VOCs and
      specific adsorptivity of the adsorbent.

PMID- 12509040
TI  - Stabilities of 58 volatile organic compounds in fused-silica-lined and SUMMA
      polished canisters under various humidified conditions.
AB  - Fused-silica-lined (FSL) canisters and SUMMA polished (SUMMA) canisters were
      compared for the recoveries and the stabilities of 58 volatile organic compounds
      (VOCs) at low ppbv (volume/volume) levels under various humidified conditions
      using a three-stage preconcentration method followed by GC-MS analysis. The
      target VOCs included non-polar VOCs (e.g. halogenated hydrocarbons and aromatic
      hydrocarbons) and polar VOCs (e.g. alcohols, ketones, esters, ethers, nitriles
      and thiols). The three-stage preconcentration method was initially optimized for
      simultaneous analysis of non-polar and polar VOCs because determination of
      canister stability is dependent on the accuracy of analytical measurements. The
      method showed good linearity over the concentration range from 1 to 25 ppbv for
      all target analytes, and the correlation coefficients were higher than 0.9974.
      The method detection limits ranged from 0.023 to 0.39 ppbv. The test mixtures
      loaded in both type of canisters (n = 3) had concentrations of 1.7-2.5 ppbv per
      compound at ambient pressure under various humidified conditions (%RH = 1.6, 8.0,
      27, 39, 53 and >99% with excess water present). All canister samples were
      initially analyzed on day 0 (after 6-12 h). The effect of competitive adsorption
      of water vapor and polar VOCs on active sites of interior surface was remarkably
      observed for SUMMA canisters. Polar VOCs had a greater requirement for water
      vapor to be present. The RH percentages that ensured good recovery on day 0 were
      RH > 8% for non-polar VOCs and RH > 27% for polar VOCs (except alcohols under the
      condition of RH > 99%). All thiols were not recovered from SUMMA canisters under
      all conditions. FSL canisters showed good recoveries of more than 86% for all
      VOCs under all conditions on day 0 (except alcohols under the condition of RH >
      99%). The recoveries of alcohols in both canisters under the condition of RH >
      99% displayed relatively low recoveries in the range 25-76% because of the
      partitioning effect into condensed water. The canister samples under the
      conditions of RH 8.0, 27, 53 and > 99% were analyzed for the stability test on
      days 3, 7, 14 and 28 after loading. All non-polar VOCs were reasonably stable in
      the FSL canisters under all examined conditions over 28 days. However, several
      polar VOCs that have relatively lower vapor pressure, e.g. MIBK, butyl acetate
      and alcohols except ethanol, showed unstable characteristics under relatively dry
      conditions (RH 8 and 27%) during 28 days. RH > 53% was needed to ensure good
      stabilities of all analytes except thiols with the recoveries of > 80% over 28
      days for both canisters. Although the FSL canister showed good recoveries of more
      than 86% for thiols on day 0, drastic degradations were observed after day 3 and
      they were not detected after day 14.

PMID- 12509041
TI  - Airborne particulate-associated polyaromatic hydrocarbons, n-alkanes, elemental
      and organic carbon in three European cities.
AB  - Total suspended particulate (TSP) samples were collected weekly over a period of
      one year at four European sites during 1995/6. Two sites were in London-a Central
      London site (CL, St Paul's Cathedral) and a suburban North London site (NL,
      Bounds Green); the other two sites were in Porto, Portugal and Vienna, Austria.
      TSP was collected using a low volume sampler. Organic carbon (OC) and elemental
      carbon (EC) concentrations were measured using a thermal-optical carbon analyser.
      Parallel samplers collected TSP for subsequent GC-MS analysis of thirty-nine
      combustion-associated organic compounds; 16 polyaromatic hydrocarbons (PAHs) and
      23 n-alkanes. OC and EC correlate well at all sites (r2 = 0.39-0.65), although
      the London inter-site correlations were low, suggesting that local sources of OC
      and EC have a significant influence on local concentrations. Concentrations do
      not vary widely across the four urban sites, despite the significant differences
      in urban characteristics. Seasonal patterns of OC:EC ratios were similar at the
      London and Vienna sites, with highest ratios in autumn and winter, and annual
      mean OC:EC ratios were identical at these sites. The Carbon Preference Index
      (CPI) indicated vehicle emissions to have a stronger influence over particulate
      concentrations at the Vienna and central London sites; there was a stronger
      biogenic signature in north London and Porto. In addition, two PAH compounds
      (pyrene and fluoranthene) previously associated with diesel exhaust, were
      correlated with OC and EC concentrations at the London and Vienna sites.

PMID- 12509042
TI  - Aerosols concentration in the Candiota area applying different gravimetric
      methods of sampling and numeric modelling.
AB  - The main purpose of the present work is to study the concentration of atmospheric
      particles in the Candiota region, in the state of Rio Grande do Sul, where the
      Presidente Medici coal power plant is located. Aerosol samples were collected at
      the studied locations between December 2000 and December 2001 during 24 h periods
      at 15 day intervals using HV PM10 and dichotomous samplers. Then, the values
      obtained with the ISCST (Industrial Source Complex Term) model, with the HV PM10
      sampler at all studied stations, and with the dichotomous sampler at the 8 de
      Agosto station were compared with each other. The results show that the values
      for the model had been underestimated in relation to the HV PM10 data for the
      studied stations, but agreed with the values obtained with the dichotomous
      sampler.

PMID- 12509043
TI  - Monitoring of ambient BTX at Monterotondo (Rome) and indoor-outdoor evaluation in
      school and domestic sites.
AB  - Results from a five month monitoring campaign of BTX (benzene, toluene and the
      sum of ethyl benzene, o-xylene, m-xylene and p-xylene), performed at
      Monterotondo, a little town 23 km NE of Rome, and correlation of the measured
      concentrations with meteorological and natural radioactivity data are presented
      and discussed. This campaign allowed us to extrapolate a pattern of the annual
      distribution of benzene in the town. A map, showing the average distribution of
      pollutants, is presented, as a useful tool to manage an appropriate policy of air
      pollution. A contemporary indoor-outdoor investigation has been performed at five
      homes and two classrooms of Monterotondo and at thirteen homes and thirteen
      classrooms in the outskirts of Rome. Non-smoking people and low polluted sites
      were chosen for this campaign, in order to highlight if commonly used domestic
      materials could act as internal sources. Data, obtained by employing long-term
      diffusive samplers, are compared with a parallel experiment showing the day-night
      indoor-outdoor trend. The obtained results, confirmed through statistical
      analysis of data, let us conclude that there is evidence of internal sources at
      homes whilst, in the schools, depletion phenomena prevail, probably due to the
      walls adsorption.

PMID- 12509044
TI  - Formation of organic by-products during chlorination of natural waters.
AB  - Natural water from six sources in Mytilene, Greece, was chlorinated in order to
      identify and quantify some of the organic by-products formed. The compounds
      examined were trihalomethanes, haloacetic acids, haloacetonitriles, haloketones,
      chloral hydrate and chloropicrin. The factors tested were time and chlorine dose.
      The presence of bromide ion in some of the waters studied resulted in significant
      changes in the by-product speciation, with enhanced brominated species formation.
      In addition, UV absorbance, measured at three wavelengths, led to correlation of
      organic matter content with the concentrations of by-products produced. The
      species formed, varying among different water sources, increased with increasing
      chlorine dose. Most of the species also increased with increasing contact time,
      although there were some exceptions due to hydrolysis reactions.

PMID- 12509045
TI  - The first monoclonal antibody-based, matrix-resistant immunoassay for the
      carbamate herbicide asulam, in water.
AB  - To date, no ligand binding assay has been described for the carbamate herbicide
      asulam, although a variety of physical methods, dependent on pre-concentration of
      water samples, have been documented for its assessment. However, asulam is
      increasingly used in sensitive agricultural areas, and statutory regulations
      concerning its monitoring will undoubtedly become more stringent. Antibodies are
      optimal partners in ligand binding assays, but it is commonly understood by
      immunological researchers that where no antibody reactive with a particular
      antigen has yet been described, the immunogenicity of the antigen may be
      particularly restricted. By the expedient of employing a specialised approach to
      final immunisation with an asulam-protein conjugate, prior to the immortalisation
      of a specific anti-asulam antibody-producing cell, we have succeeded in
      generating a monoclonal antibody reactive specifically with asulam that can be
      configured in a convenient immunoassay. This antibody may be used flexibly in a
      number of ways: small sample volumes of 10 microl can be assessed to
      sensitivities of 4.35 x 10(-7) M (10 microg L(-1)) while avoiding discrepancies
      contributed by the assay matrix; this antibody-based assay can also be formatted
      to deliver sensitivities at levels stipulated by regulatory authorities (e.g.,
      4.35 x 10(-9) M or 0.1 microg L(-1)) directly from a water sample, without prior
      pre-concentration.

PMID- 12509046
TI  - Dissolved insecticides and polychlorinated biphenyls in the Pearl River Estuary
      and South China Sea.
AB  - Persistent organic pollutants (POPs) such as organochlorine (OCl) insecticides
      and polychlorinated biphenyls (PCB), together with the new generation of
      organophosphorus (OP) insecticides, are of global concern, due to their
      widespread occurrence, persistence, bioaccumulation and hormone disruption
      potential. This paper represents an attempt to study the source and
      transportation of such pollutants in estuarine and coastal environments as an
      integrated ecosystem, by determining the levels of 18 OCl insecticides, 21 PCB
      congeners, and 17 OP insecticides in the Pearl River Estuary and South China Sea.
      The total concentrations varied from 126-1198 ng l(-1) for OCl insecticides,
      33.38-1064 ng l(-1) for PCB congeners, and 4.44-6356 ng l(-1) for OP insecticides
      in the Pearl River Estuary. In comparison, their levels in the South China Sea
      were significantly lower, varying from 57.09-202 ng l(-1) for OCl insecticides,
      21.72-144 ng l(-1) for PCBs, and 1.27-122 ng l(-1) for OP insecticides,
      respectively. The predominance of beta-HCH in HCHs, and DDE in DDTs in all water
      samples was clearly observed, suggesting beta-HCH and DDE's resistance to further
      degradation. The PCBs were dominated by those with 3-6 chlorines. The
      distribution characteristic of OP insecticides shows that five compounds
      (methamidophos, dimethoate, malathion, dichlorvos and omethoate) accounted for
      56% and 72% of the total OP insecticide concentration. The relationship between
      pollutant concentrations and salinity in the estuary showed that they were all
      removed during the mixing process, therefore behaving non-conservatively.

PMID- 12509047
TI  - Multivariate analysis of the bioaccumulation of polychlorinated biphenyls (PCBs)
      in the marine pelagic food web from the southern part of the Baltic Sea, Poland.
AB  - The concentration, pattern, bioaccumulation and biomagnification features of many
      chlorobiphenyl congeners including non- and mono-ortho chlorine substituted
      members have been determined in a pelagic food chain including mixed phyto- and
      zooplankton, herring (Clupea harengus), harbour porpoise (Phocoena phocoena) and
      black cormorants (Phalacrocorax carbo sinensis) collected from the southern part
      of the Baltic Proper. TCDD (tetrachlorodibenzo-p-dioxin) toxic equivalents (TEQs)
      in plankton, herring, harbour porpoise and cormorants were 0.42, 5.3, 79 and
      2,700 pg g(-1) lipid weight, respectively. Concentrations of total
      polychlorinated biphenyls (PCBs) in plankton, herring, harbour porpoise and
      cormorants were 1.9, 120, 8700 and 2,100 ng g(-1) wet weight (210, 1,300, 10,000
      and 42,000 ng g(-1) lipid weight) respectively. Herring, harbour porpoise and
      black cormorant apparently bioaccumulate many PCBs found in their food, and the
      values of the bioaccumulation factors (BAFs) for PCBs were approximately 10 in
      herring, 35 in harbour porpoise and up to 300 in breast muscle of cormorants.
      Harbour porpoise clearly is able to metabolize the most toxic non-ortho PCBs (no.
      77, 126 and 169) and a few mono-ortho PCBs (no. 114, 123 and 156), while all non-
      and mono-ortho PCBs are bioaccumulated by herring. Penta-, hexa- and hepta-CBs
      were the dominatant homologue classes both in the muscle tissue and liver. PCB
      congeners nos. 201, 209, 172/192, 194 and 195 were characterized by the largest
      BAFs (between 100 and 300). Principal component analysis has been used to analyse
      the interdependences and differences in the CB congener accumulation patterns
      between the components of the investigated pelagic food web.

PMID- 12509048
TI  - Characterization of elemental pollution and its variations in sediments and
      suspended particulate matter from the River Elbe via multi-element analysis
      combined with chemometric data evaluation.
AB  - Sediments and suspended particulate matter taken from about 100 sampling sites
      along the River Elbe from the source to the mouth during the period 1992 and 1998
      have been analyzed for the concentrations of more than 60 elements in each
      sample. The analytical data were subsequently processed by means of multivariate
      statistics in order to characterize the charge of the River Elbe with inorganic
      pollutants to elucidate pollution trends. Using factor analysis 18 elements were
      found to be enriched by human activities. By means of cluster analysis--using the
      18 anthropogenically influenced elements as variables--the sampling sites were
      aggregated into groups having similar element distributions. Thus, the entire
      stretch of the River Elbe was divided into three sections of characteristic
      elemental pollution. Finally, the trends in anthropogenic pollution within the
      characteristic regions since the early nineties were assessed. It turned out that
      most of the anthropogenically influenced elements showed a decrease in the upper
      and middle parts of the river, whereas no decrease could be verified in the
      estuary region.

PMID- 12509049
TI  - An ultrasound accelerated sequential extraction method and its application for
      element partitioning studies in compost from mixed waste streams.
AB  - A rapid ultrasound accelerated sequential extraction procedure is presented which
      is modified from the standard BCR protocol and validated using the BCR 601
      reference material. The method is accelerated at the extraction steps: for
      example, in the standard method each extraction step takes 16 h whereas with the
      ultrasonic extraction method developed in this work each step took 15 min. This
      means a further step can be included in the protocol without greatly increasing
      the experimental time. An extraction with pyrophosphate solution was therefore
      included to provide more information about the interaction between the elements
      and humic substances during the composting process. The new method has been
      applied to monitoring the metal partitioning behaviours in a composting process
      involving mixed waste streams. The metal partitioning profiles obtained from this
      new method show that in many cases composting tends to redistribute the metals
      from more labile forms to combined forms, especially to forms combined with humic
      substances.

PMID- 12509050
TI  - Study on determination of iron, cobalt, nickel, copper, zinc and manganese in
      drinking water by solid-phase extraction and RP-HPLC with 2-(2-quinolinylazo)-5
      diethylaminophenol as precolumn derivatizing reagent.
AB  - A new method for the determination of iron, cobalt, nickel, copper, zinc and
      manganese in drinking water by the reversed-phase high-performance liquid
      chromatography (RP-HPLC) with 2-(2-quinolinylazo)-5-diethylaminophenol (QADEAP)
      as precolumn derivatizing reagent was studied in this paper. The iron, cobalt,
      nickel, copper, zinc, and manganese ions react with QADEAP to form color chelates
      in the presence of cetyl trimethylammonium bromide (CTMAB) and acetic acid-sodium
      acetic buffer solution medium of pH 4.0. These chelates were enriched by solid
      phase extraction with a Waters Nova-Pak C18 cartridge and eluted the retained
      chelates from the cartridge with tetrahydrofuran (THF). The enrichment factor of
      100 was achieved. Then the chelates were separated on a Waters Nova-Pak C18
      column (3.9 x 150 mm, 5 microm) by gradient elution with methanol (containing
      0.2% of acetic acid and 0.1% of CTMAB) and 0.05 mol L(-1) acetic acid-sodium
      acetic buffer solution (containing 0.1% of CTMAB) (pH 4.0) as mobile phase at a
      flow rate of 0.5 ml min(-1), and monitored with a photodiode array detector from
      450 approximately 700 nm. The detection limits (S/N = 3) of iron, cobalt, nickel,
      copper, zinc and manganese are 0.8, 1.1, 0.9, 1.1, 1.5 and 2.0 ng L(-1),
      respectively, in the original sample. This method can be applied to determination
      at the microg L(-1) level of iron, cobalt, nickel, copper, zinc and manganese in
      drinking water with good results.

PMID- 12509051
TI  - Seasonal variations in nickel and vanadium in Mont Blanc snow and ice dated from
      the 1960s and 1990s.
AB  - Ni and V have been determined in snow and ice collected at a high altitude
      location (Col du Dome) near the summit of Mont Blanc on the French-Italian
      border; dated from the 1960s and 1990s. Ni and V were simultaneously determined
      by inductively coupled plasma sector field mass spectrometry. Measured
      concentrations range from 6 to 700 pg g(-1) and 4 to 1,100 pg g(-1) for Ni and V,
      respectively. The results show pronounced seasonal variations in the
      concentrations of both metals, with high concentration values in summer layers
      and much lower values for winter layers. These seasonal variations are linked
      especially with the existence of inversion layers during winter months. Ni and V
      concentrations in excess of the contributions from rock and soil dust
      (Ni(excess), V(excess)) appear to be mainly associated with anthropogenic inputs,
      with pronounced seasonal variations. Large variations in the V(excess)/Ni(excess)
      ratio are observed, with a higher ratio in summer than in winter. This shows
      differences in anthropogenic inputs at Col du Dome during the different parts of
      the year. The above ratio was compared with the corresponding ratios for oil
      combustion from stationary sources and the exhaust from gasoline and diesel
      engines. It appears that Ni and V concentrations at Col du Dome are probably the
      result of changing combinations of contributions from oil combustion for power
      generation, industrial and residential uses, on one side, and automobile and
      truck traffic, on the other side, with possibly a significant contribution from
      Ni smelters in Russia during winter months.

PMID- 12509052
TI  - Accumulation of metals in the soil of an overland flow wastewater treatment
      system.
AB  - Accumulation of Co, Cu, Cr, Mo, Ni, Pb and Zn was evaluated in a soil profile of
      an overland flow system used for the post-treatment of urban wastewater. A pilot
      version of the overland flow system received urban wastewater from five up-flow
      anaerobic filters filled with bamboo (Bambusa tuldoides) rings. The anaerobic
      effluent was applied as feed over 18 months at rates varying from 7 to 28 L min(
      1), to a vegetated slope length covered with Tifton 85 (Cynodon) sp. grass. Soil
      and plant samples were collected in triplicate from the top to the bottom of the
      slope. In addition, the soils were sampled at the depths 0-20 and 20-40 cm. The
      metal concentrations found in the overall system were compared to those obtained
      in a control area located at the beginning of the slope onto which nothing was
      applied. A month of monitoring the urban wastewater of Limeira City (Sao Paulo
      State, Brazil) showed a drastic change in metals concentration due to the
      irregular discharge of industrial waste. This irregular discharge introduces Cr,
      Cu, Ni, Pb and Zn into the system used to treat domestic wastewater. The mass
      balance indicates the accumulation of metals in the soil and the translocation to
      the plants; also that they could be evapotranspirated, percolated and discharged.

PMID- 12509053
TI  - Fractionation of elements by particle size of ashes ejected from Copahue Volcano,
      Argentina.
AB  - The volcano Copahue, Neuquen province, Argentina has shown infrequent explosive
      eruptions since the 18th century. Recently, eruptive activity and seismicity were
      registered in the period July-October, 2000. As a consequence, ash clouds were
      dispersed by winds and affected Caviahue village located at about 9 km east of
      the volcano. Samples of deposited particles from this area were collected during
      this episode for their chemical analysis to determine elements of concern with
      respect to the health of the local population and its environment. Different
      techniques were used to evaluate the distribution of elements in four particle
      size ranges from 36 to 300 microm. X-ray powder diffraction (XRD) was selected to
      detect major components namely, minerals, silicate glass, fragments of rocks and
      sulfurs. Major and minor elements (Al, Ca, Cl, Fe, K, Mg, Mn, Na, S, Si and Ti),
      were detected by energy dispersive X ray analysis (EDAX). Trace element (As, Cd,
      Cr, Cu, Hg, Ni, Pb, Sb, U, V and Zn) content was quantified by inductively
      coupled plasma-mass spectrometry (ICP-MS). Nuclear activation analysis (NAA) was
      employed for the determination of Ce, Co, Cs, Eu, Hf, La, Lu, Rb, Sc, Sm, Ta and
      Yb. An enrichment was observed in the smallest size fraction of volcanic ashes
      for four elements (As, Cd, Cu and Sb) of particular interest from the
      environmental and human health point of view.

PMID- 12509054
TI  - Adsorption and detection of some phenolic compounds by rice husk ash of Kenyan
      origin.
AB  - Rice husk ash (RHA) obtained from a rice mill in Kenya has been used as an
      inexpensive and effective adsorbent (and reagent) for the removal (and detection)
      of some phenolic compounds in water. The abundantly available rice mill waste was
      used in dual laboratory-scale batch experiments to evaluate its potential in: (i)
      the removal of phenol, 1,3-dihydroxybenzene (resorcinol) and 2-chlorophenol from
      water; and (ii) the detection of 1,2-dihydroxybenzene (pyrocatechol) and 1,2,3
      trihydroxybenzene (pyrogallol) present in an aqueous medium. The studies were
      conducted using synthetic water with different initial concentrations of the
      phenolic compounds. The effects of different operating conditions (such as
      contact time, concentration of the phenolic compounds, adsorbent quantity,
      temperature, and pH) were assessed by evaluating the phenolic compound removal
      efficiency as well as the extent of their color formation reactions (where
      applicable). RHA exhibits reasonable adsorption capacity for the phenolic
      compounds and follows both Langmuir and Freundlich isotherm models. Adsorption
      capacities of 1.53 x 10(-4), 8.07 x 10(-5), and 1.63 x 10(-6) mol g(-1) were
      determined for phenol, resorcinol and 2-chlorophenol, respectively. Nearly 100%
      adsorption of the phenolic compounds was possible and this depended on the weight
      of RHA employed. For the detection experiments, pyrocatechol and pyrogallol
      present in water formed coloured complexes with RHA, with the rate of colour
      formation increasing with temperature, weight of RHA, concentration of the
      phenolic compounds and sonication. This study has proven that RHA is a useful
      agricultural waste product for the removal and detection of some phenolic
      compounds.

PMID- 12509055
TI  - Atmospheric deposition of major ions and trace metals near an industrial area,
      Jordan.
AB  - Al, Cd, Cr, Cu, Fe, Mn, Pb, Zn, NH4+, Mg2+, Ca2+, Na+, K+, Cl-, NO3- and SO4(2-),
      along with pH were determined in wet and dry deposition samples collected at Al
      Hashimya, Jordan. Mean trace metal concentrations were similar or less than those
      reported for other urban regions worldwide, while concentrations of Ca2+ and
      SO4(2-) were the highest. The high Ca2+ concentrations were attributed to the
      calcareous nature of the local soil and to the influence of the Saharan dust,
      while the high concentrations of SO4(2-) were attributed to the influence of
      anthropogenic sources and Saharan dust soil. Except for SO4(2-), NO3-, and Ca2+,
      dry deposition fluxes of measured metals and ions were higher than their
      corresponding wet deposition fluxes. The high annual average pH values recorded
      for wet and dry deposition samples were attributed to the neutralization of
      acidity by alkaline species. Cd, Cr, Cu, Pb, Zn, NO3- and SO4(2-) were enriched
      in wet and dry deposition samples relative to crustal material, and a significant
      anthropogenic contribution to these elements and ions is tentatively suggested.
      Finally, the possible sources and the main factors affecting the concentrations
      of the measured species are discussed.

PMID- 12509056
TI  - Water-soluble species and heavy metal contamination of the petroleum refinary
      area, Jordan.
AB  - The levels of lead, cadmium, copper, zinc, aluminum, chromium, and iron in street
      dust, soil, and plants in the Jordanian petroleum refinery were determined using
      flame and graphite-furnace atomic absorption spectrophotometry. Major cations
      (Li+, Na+, NH4+, K+, Mg2+, and Ca2+) and anions (F-, Cl-, NO3-, SO4(2-), and Br-)
      were also determined using suppression mode ion chromatography. Generally, higher
      levels of the heavy metals studied were found in street dust samples than in soil
      samples. On the other hand, except Cl-, and Li+ ions, other anions and cations
      showed higher concentrations in soil than in street dust samples. For plant
      samples, unwashed samples showed higher levels of heavy metals than their washed
      counterparts, indicating that dust fall is a source of heavy metal contamination.

PMID- 12509057
TI  - Determination of irradiated reactor uranium in soil samples in Belarus using 236U
      as irradiated uranium tracer.
AB  - This work presents experimental results on the distribution of irradiated reactor
      uranium from fallout after the accident at Chernobyl Nuclear Power Plant (NPP) in
      comparison to natural uranium distribution in different soil types. Oxidation
      processes and vertical migration of irradiated uranium in soils typical of the 30
      km relocation area around Chernobyl NPP were studied using 236U as the tracer for
      irradiated reactor uranium and inductively coupled plasma mass spectrometry as
      the analytical method for uranium isotope ratio measurements. Measurements of
      natural uranium yielded significant variations of its concentration in upper soil
      layers from 2 x 10(-7) g g(-1) to 3.4 x 10(-6) g g(-1). Concentrations of
      irradiated uranium in the upper 0-10 cm soil layers at the investigated sampling
      sites varied from 5 x 10(-12) g g(-1) to 2 x 10(-6) g g(-1) depending on the
      distance from Chernobyl NPP. In the majority of investigated soil profiles 78% to
      97% of irradiated "Chernobyl" uranium is still contained in the upper 0-10 cm
      soil layers. The physical and chemical characteristics of the soil do not have
      any significant influence on processes of fuel particle destruction. Results
      obtained using carbonate leaching of 236U confirmed that more than 60% of
      irradiated "Chernobyl" uranium is still in a tetravalent form, ie. it is included
      in the fuel matrix (non-oxidized fuel UO2). The average value of the destruction
      rate of fuel particles determined for the Western radioactive trace (k = 0.030 +/
      0.005 yr(-1)) and for the Northern radioactive trace (k = 0.035 + 0.009 yr(-1))
      coincide within experimental errors. Use of leaching of fission products in
      comparison to leaching of uranium for study of the destruction rate of fuel
      particles yielded poor coincidence due to the fact that use of fission products
      does not take into account differences in the chemical properties of fission
      products and fuel matrix (uranium).

PMID- 12509058
TI  - Comparison of leaching tests for the study of trace metals remobilisation in
      soils and sediments.
AB  - Several leaching tests were applied and compared to study metal remobilisation on
      various unpolluted and contaminated soils and on several contaminated sediments.
      The trace elements considered were Cd, Cr, Cu, Ni, Pb and Zn, and leaching tests
      consisted of the application of reagents with contrasting characteristics and
      strengths in order to assess the information provided. An extraction with aqua
      regia permitted the estimation of the pseudo-total metal content in the sample.
      Mild extractants such as H2O, CaCl2 and NaNO3 showed low and similar leaching
      capacities. Acid (CH3COOH) and complexing (EDTA) agents were more effective in
      remobilising trace metals from soils and sediments. Cd and Zn showed similar
      extraction characteristics under both extractant solutions, whereas Cu and Pb
      were more sensitive to complexation, and Ni and Cr to acidification processes.
      Sequential chemical extractions provided additional information on the
      association of the trace elements with the different soil and sediment phases. Cd
      and Zn showed the highest mobility, Pb was associated to reducible solid phases,
      Cu and Ni to oxidisable phases, and Cr remained mostly in the residual fraction.
      The results obtained in this paper provided valuable information for choosing a
      leaching test, which is an instrument of environmental analysis for the
      estimation of trace metal mobility.

PMID- 12509059
TI  - SEC-ICP-MS studies for elements binding to different molecular weight fractions
      of humic substances in compost extract obtained from urban solid waste.
AB  - In this work, the speciation of elements in compost was studied with emphasis on
      their binding to humic substances. In order to assess the distribution of As, Cd,
      Co, Cr, Cu, Mn, Mo, Ni, Pb, U, Th and Zn among molecular weight fractions of
      humic substances, the compost extract (extracted by 0.1 mol l(-1) sodium
      pyrophosphate) was analyzed by size exclusion chromatography coupled on-line with
      UV-Vis spectrophotometric and ICP-MS detection. Similar chromatograms were
      obtained for standard humic acid (Fluka) and for compost extract (254 nm, 400 nm)
      and three size fractions were operationally defined that corresponded to the
      apparent molecular weight ranges > 15 kDa, 1-15 kDa and < 1 kDa. The percentage
      of total element content in compost that was leached to the extract ranged from
      30% up to 100% for different elements. The elution profiles of Co, Cr, Cu, Ni and
      Pb (ICP-MS) followed that of humic substances, while for other elements the bulk
      elution peak matched the retention time observed for the element in the absence
      of compost extract. Spiking experiments were carried out to confirm elements'
      binding and to estimate the affinity of individual elements for humic substances
      derived from compost. The results obtained indicated the following order of
      decreasing affinity: Cu > Ni > Co > Pb > Cd > (Cr, U, Th) >> (As, Mn, Mo, Zn).
      After standard addition, further binding of Cu, Ni and Co with the two molecular
      weight fractions of humic substances was observed, indicating that humic
      substances derived from compost were not saturated with these elements.

PMID- 12509060
TI  - Portable X-ray fluorescence in the characterisation of arsenic contamination
      associated with industrial buildings at a heritage arsenic works site near
      Redruth, Cornwall, UK.
AB  - An investigation using in situ analysis by portable X-ray fluorescence (PXRF) has
      shown that contamination present on industrial buildings at a heritage arsenic
      works site near Redruth, Cornwall, UK results from the absorption of arsenic by
      porous and semi-porous building materials that were in contact with arsenic-rich
      flue gases. Results from a preliminary survey indicate that arsenic remains
      locked in these materials and is being gradually leached out by weathering
      processes. This weathering causes general contamination of the adjacent building
      surfaces averaging 1845 microg g(-1) arsenic, presumably caused by evaporation of
      leach solutions in contact with air at the surface of the building materials.
      More extensive crystalline deposits were found under arches protected from
      dissolution and further dispersion by rain water. These deposits appeared to
      comprise calcium sulfate (gypsum), associated with on average between 1.2 and
      6.8% m/m As. In situ PXRF proved to be highly effective in locating sources of
      contamination at the site and in providing data that allowed a hypotheses for the
      origin of this contamination to be formulated and tested in the field.

PMID- 12509061
TI  - A comparison of methods and materials for the analysis of leaded wipes.
AB  - The purposes of this study are: (1) to determine whether proficiency analytical
      test (PAT) materials from the American Industrial Hygiene Association can be used
      to provide quality data for portable X-ray fluorescence analysis (XRF) of lead in
      dust wipe surface samples; (2) to provide data to determine whether the on-site
      analysis of field dust wipe samples by XRF and the laboratory method of
      inductively coupled plasma emission analysis (ICP) are comparable; and (3) to
      determine if differences exist between different wipe materials. Several wipes
      meet the ASTM E1792 performance requirements of lead background level less than 5
      microg per wipe, be only one layer thick, yield recovery rates of 80- 120% from
      spiked samples, remain damp throughout the sampling procedure, and do not contain
      aloe. The wipes used in this study were Pace Wipes, which are used for the PAT
      materials, and, for the field samples, Palintest Wipes, which were supplied by
      the instrument manufacturer, and Ghost Wipes, which are popular because they
      digest in hot, concentrated acid, so that chemical analysis is simplified. Twenty
      PAT wipe samples were obtained from four different proficiency test rounds.
      Surface wipe samples were taken at three different locations representing
      different industry types. All samples were analyzed using a portable XRF
      spectrometer and by ICP. Strong linear relationships were found for the analysis
      of wipe samples by ICP and by portable XRF. For the PAT samples, the results from
      the ICP and XRF analysis were not statistically equivalent, which indicates a
      bias in the ICP analysis. The bias was not excessive, since all ICP analyses fell
      within the acceptable range for the proficiency samples. The good correlation
      between the proficiency sample reference values and the XRF determinations is not
      surprising considering similar proficiency samples were used to calibrate the
      instrument response. Users of this portable XRF analyzer could enroll in the
      proficiency test program as part of their quality assurance program. For field
      samples, the relationship was strongest for Palintest wipes, and the values found
      for all three industries could be combined. However, the results from the ICP and
      XRF analysis were not statistically equivalent using the correction factor in the
      calculation algorithm as supplied with the instrument, and a new coefficient was
      derived. The mean relative error for the XRF analysis versus the ICP analysis was
      greater than 25%, such that the method falls within the realm of screening
      procedures. For Ghost Wipe samples, the precision was different for different
      industries, and the results could not be pooled. Differences between the two wipe
      materials may be related to the number of folds required for analysis.

PMID- 12509062
TI  - Age dependence of potentially toxic elements (Sb, Cd, Pb, Ag) in human liver
      tissue from paediatric subjects.
AB  - Toxic elements are present at low concentrations in the environment. This work
      was undertaken to investigate the age dependence of the liver content of selected
      elements in paediatric populations, as an index of internal exposure. Liver
      samples were collected at autopsy from 157 subjects, aged < 1 day to 6 years, as
      part of investigations on a possible role of Sb compounds in sudden infant death
      syndrome (SIDS). In addition to Sb, the concentrations of Ag, Cd and Pb were also
      determined by inductively coupled plasma mass spectrometry on the remaining
      digest. Comparison of 95% confidence intervals of the median concentrations of
      the four elements suggested that there were no differences between the two
      categories of cause of death, SIDS or those who had died of an identified
      disease. Cadmium, lead and antimony median concentrations were lower than
      corresponding values observed in adult populations. Silver concentrations were
      significantly higher at birth and decreased with age. Cadmium levels were almost
      negligible in neonates and infants, but increased in older children. The finding
      of non-negligible concentrations of both Ag and Pb in neonatal liver provides
      further direct evidence that these elements cross the human placental barrier.
      The reported data, by far the largest collection observed in subjects less than 1
      year old, are the result of exposure, during pregnancy and in early childhood, to
      present levels of these elements in the environment. They can serve as a
      reference to compare post-mortem values from individuals or groups of subjects in
      this age range when an exposure risk is suspected and to highlight trends in
      human exposure.

PMID- 12509063
TI  - Determination of estrogenic activity in landfill leachate by simplified yeast two
      hybrid assay.
AB  - We previously developed a simplified yeast two-hybrid assay of estrogenic
      activity. In the present study, the optimal conditions for sensitivity and
      stability of this assay were decided. The assay could determine the estrogenic
      activity of 4 x 10(-11) mol dm(-1) 17beta-estradiol and also anti-estrogenic
      activity by using 4-hydroxytamoxifen as a control. The assay was used to test
      various chemicals suspected of estrogenicity. Many kinds of chemical, including
      alkylphenols, naphthols, xylenols, methoxychlor, phthalates, and bisphenol-A,
      showed estrogenic activity, and several, such as 2,5-xylenol and di-iso-octyl
      phthalate, showed anti-estrogenic but no estrogenic activity. Copresence of two
      estrogenic chemicals produced additive activity. The assay was also used to test
      leachate and water samples from the sea-based landfill of Osaka North Port in
      Japan. Estrogenic activity was detected in leachate from a municipal waste
      dumping site, but not in that from a dredged soil-dumping site, which did however
      cause inhibition of cell growth.

PMID- 12509064
TI  - Comparison of SFE with Soxhlet in the analyses of PCDD/PCDFs and PCBs in
      sediment.
AB  - The efficiency of supercritical fluid extraction (SFE) for the isolation of
      polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDD) and dibenzofurans
      (PCDF) from sediments was investigated by comparing SFE with Soxhlet. Five
      sediments obtained from an international interlaboratory study were used as a
      test material. SFE was performed with an automatic system where extracted
      analytes were collected by solid-phase trapping using carbon mixed with Celite as
      an adsorbent. For the first time, SFE of the most toxic PCBs, coplanar PCBs, was
      studied with real sediment samples. The majority of PCBs investigated, a total of
      38 congeners from tri- to decachlorinated, were quantitatively extracted from
      sediment by SFE with pure CO2 at pressure 400 atm and temperature 100 degrees C.
      Under these conditions a successful extraction was obtained also for PCDD/PCDFs
      except for hepta- and octachlorinated congeners. Copper powder added to the
      sediment efficiently prevented the transfer of sulfur from the sample during SFE.
      The TEQs of both PCDD/PCDFs and PCBs obtained by SFE corresponded well with those
      obtained by the Soxhlet-based method. The reproducibility of SFE was high for
      both groups.

PMID- 12509065
TI  - Occupational exposure to rubber vulcanization products during repair of rubber
      conveyor belts in a brown coal mine.
AB  - Several hundred chemical compounds were found in workroom environments in the
      rubber industry, but most of the published exposure data relate to the production
      of tyres; information from the "non-tyre" sections are very limited, if any. This
      study was carried out to identify chemical substances and measure their air
      concentrations in the repair shop of a brown coal mine in which damaged rubber
      conveyor belts were repaired. GC-MS and HPLC analysis of stationary air samples
      resulted in identification of aliphatic and aromatic hydrocarbons to C12, PAHs,
      alcohols, phenols, ketones, heterocyclic nitrogen and sulfur compounds.
      Quantitative evaluation of occupational exposure included determination of
      organic compound vapours collected on charcoal (GC-MSD), polycyclic aromatic
      hydrocarbons (HPLC), N-nitrosoamines and other amines (GC-NPD) and DNPH
      derivatives of aldehydes (HPLC) in the breathing zone of workers representing all
      job titles. The concentrations of investigated compounds were very low.
      Carcinogenic substances: N-nitrosoamines, benzene, PAHs were not present in
      workroom air in concentrations exceeding limits of detection of the analytical
      methods being applied; concentrations of methylisobutylketone,
      tetrachloroethylene, naphtha, aromatic hydrocarbons, phthalates and aldehydes
      were much lower than the respective occupational exposure limit values. The
      results indicate much lower exposure than that reported in the production of
      tyres and other fabricated rubber products.

PMID- 12509066
TI  - Selenium intake, mood and other aspects of psychological functioning.
AB  - Selenium is an essential trace element although the level of selenium in food
      items reflects the soil in which they were grown and thus varies markedly between
      different parts of the world. The metabolism of selenium by the brain differs
      from other organs in that at times of deficiency the brain retains selenium to a
      greater extent. The preferential retention of selenium in the brain suggests that
      it plays important functions. To date mood is the clearest example of an aspect
      of psychological functioning that is modified by selenium intake. Five studies
      have reported that a low selenium intake was associated with poorer mood. The
      underlying mechanism is unclear although a response to supplementation was found
      with doses greater than those needed to produce maximal activity of the
      selenoprotein glutathione peroxidase. Although the functions of many
      selenoproteins are unknown some play important roles in anti-oxidant mechanisms.
      As there are suggestions that oxidative injury plays a role in normal aging,
      schizophrenia, Parkinson's and Alzheimer's disease, the possible role of selenium
      is considered. Although there is evidence that supplementation with anti-oxidant
      vitamins shown some promise with Alzheimer's patients, and in preventing the
      development of tardive dyskinesia in schizophrenics taking neuroleptics, a role
      for selenium has been little considered.

PMID- 12509067
TI  - Magnesium and affective disorders.
AB  - There are several findings on the action of magnesium ions supporting their
      possible therapeutic potential in affective disorders. Examinations of the sleep
      electroencephalogram (EEG) and of endocrine systems point to the involvement of
      the limbic-hypothalamus-pituitary-adrenocortical axis as magnesium affects all
      elements of this system. Magnesium has the property to suppress hippocampal
      kindling, to reduce the release of adrenocorticotrophic hormone (ACTH) and to
      affect adrenocortical sensitivity to ACTH. The role of magnesium in the central
      nervous system could be mediated via the N-methyl-D-aspartate-antagonistic, gamma
      aminobutyric acidA-agonistic or a angiotensin II-antagonistic property of this
      ion. A direct impact of magnesium on the function of the transport protein p
      glycoprotein at the level of the blood-brain barrier has also been demonstrated,
      possibly influencing the access of corticosteroids to the brain. Furthermore,
      magnesium dampens the calciumion-proteinkinase C related neurotransmission and
      stimulates the Na-K-ATPase. All these systems have been reported to be involved
      in the pathophysiology of depression. Despite the antagonism of lithium to
      magnesium in some cell-based experimental systems, similarities exist on the
      functional level, i.e. with respect to kindling, sleep-EEG and endocrine effects.
      Controlled clinical trials examining the effect of Mg in affective disorder are
      warranted.

PMID- 12509068
TI  - Birthdates and number of neurons in the serotonergic raphe nuclei in the rat with
      prenatal protein malnutrition.
AB  - The effect of prenatal protein deprivation on timing of neurogenesis and on
      number of neurons generated in the serotonergic dorsal (DR) and median raphe (MR)
      nuclei of the rat was studied. These neurons are of interest because their
      neurogenesis occurs during the period of malnutrition and their axonal
      projections participate in the earliest stages of brain development. In this
      study, dams were maintained on a 25% casein diet or a 6% casein diet 5 weeks
      prior to mating and throughout pregnancy. At birth, all pups were cross-fostered
      to dams on a 25% casein diet. Bromodeoxyuridine, a thymidine analog that is
      incorporated into nuclear deoxyribonucleic acid during the cell cycle synthetic
      phase, was used as a marker of neurogenesis. Bromodeoxyuridine was administered
      on either embryonic day 11, 12, 13 or 14. On postnatal day 30, serial sections of
      raphe nuclei were processed with bromodeoxyuridine immunocytochemistry to
      determine the number of raphe cells generated on each day and with Nissl stain to
      determine the total number of cells generated. There were no significant
      differences between the two diet groups in timing of generation or in total
      number of cells generated, indicating that neurogenesis of these early generated
      neurons appears unaffected by concomitant protein deprivation.

PMID- 12509069
TI  - Retrieving of pups by neonatally stressed mothers.
AB  - In the rat, perinatal food and maternal deprivation provoke long-lasting effects
      upon the retrieving responses of dams to displaced pups. In the current study,
      the retrieving latency and the disruption in the body area of pups chosen by the
      mother to transport them to a new location was investigated on days 4, 8 and 12
      postpartum in lactating Wistar rats. Rats, neonatally underfed by daily (12 h)
      mother-litter separation in an incubator from days 1 to 23 postpartum, exhibited
      prolonged retrieving latencies and disruption in the body area of young ones
      chosen by the dam to transport them to the nest. Furthermore, neonatally underfed
      dams frequently transported pups in a rude manner eliciting sonic distress cries
      from them compared to control mothers. These findings are possibly relevant to
      understand the impact of epigenetic influences on offspring brain and
      physiological maturation partly mediated through maternal care.

PMID- 12509070
TI  - The effects of dietary sulfur amino acid deficiency on rat brain glutathione
      concentration and neural damage in global hemispheric hypoxia-ischemia.
AB  - Primary brain injury in stroke is followed by an excitotoxic cascade, oxidative
      stress and further neural damage. Glutathione is critical and depleted in
      oxidative stress. Since cysteine is limiting in glutathione synthesis, this study
      investigated the effect of dietary sulfur amino acid (SAA) deficiency on neural
      damage in a rat model of global hemispheric hypoxia-ischemia (GHHI). Animals were
      fed with SAA deficient ("deficient") or control diet for 3 days, subjected to
      right common carotid artery ligation and hypoxia, and diet continued for 3 more
      days. Histologically evaluated neural damage at 7 days post hypoxia-ischemia was
      greater in "deficient" rats, shown by mean (+/- SEM) global and hippocampal grid
      scores of 2.5 +/- 0.7 and 34.9 +/- 9.3%, respectively, vs. controls' scores of
      0.1 +/- 0.1 and 0.1 +/- 0.1%, respectively. Mean brain (+/- SEM) reduced
      glutathione was not different between groups at 6h post hypoxia-ischemia, but was
      decreased in "deficient" animals 3 days later in neocortex (1.46 micromoles/g wet
      weight +/- 0.05 vs. 1.67 +/- 0.04 in controls) and thalamus (1.60 micromoles/g
      wet weight +/- 0.05 vs. 1.78 +/- 0.03 in controls). Administration of a cysteine
      precursor to "deficient" animals did not ameliorate neural damage. These findings
      suggest that well-nourished but not "deficient" animals tolerate a mild brain
      insult. The decline in brain glutathione in the "deficient" animals may be one of
      several contributing mechanisms.

PMID- 12509071
TI  - The induction of low nocturnal secretion of melatonin caused by reverse feeding
      rhythms depends on availability of macronutrient diets.
AB  - The present study investigated the effect of single chow diet and two-way dietary
      choice between a protein-rich and a carbohydrate-rich diet ingested during free
      access or daytime access (08.00-16.00 h) on the rhythms of ingestion and on
      nocturnal levels of serum melatonin and pineal N-acetyltransferase activity in
      rats. Animals with free access to the single or the choice diets displayed a
      circadian rhythmicity of total food intake with peaks at the beginning, the
      middle and the end of the dark phase. Rats fed the dietary choice displayed a
      preference for carbohydrate at the beginning, and a preference for protein at the
      middle and the end of the dark phase. Under daytime feeding access, both dietary
      conditions resulted in only one peak of total intake at the beginning of the
      access period. Rats fed the choice diets on the daytime feeding schedule
      initially preferred carbohydrate to protein but this preference disappeared
      subsequently. Nocturnal peaks of serum melatonin and pineal NAT activity were
      lower with daytime access to dietary choice compared to ad libitum access. The
      results suggest that in a two-way selection of macronutrients, feeding cycle can
      directly act on the rhythms expressed within the pineal gland.

PMID- 12509072
TI  - Feeding rats diets enriched in lowbush blueberries for six weeks decreases
      ischemia-induced brain damage.
AB  - Oxidative stress is an important element in the etiology of ischemic stroke.
      Lowbush blueberries (Vaccinium angustifolium Aiton) have a high antioxidant
      capacity and thus we determined whether consumption of lowbush blueberries would
      protect neurons from stroke-induced damage. Rats were fed AIN-93G diets
      containing 0 or 14.3% blueberries (g fresh weight/100 g feed) for 6 weeks. Stroke
      was then simulated by ligation of the left common carotid artery (ischemia),
      followed by hypoxia. One week later, plasma and urine were collected, and
      neuronal damage in the hippocampus was determined histologically. In control
      rats, hypoxia-ischemia resulted in 40 +/- 2% loss of neurons in the hippocampus
      of the left cerebral hemisphere, as compared to the right hemisphere. Rats on
      blueberry-supplemented diets lost only 17 +/- 2% of neurons in the ischemic
      hippocampus. Neuroprotection was observed in the CA1 and CA2 regions, but not CA3
      region, of the hippocampus. The blueberry diet had no detectable effects on the
      plasma or urine oxygen radical absorbance capacity (ORAC) or plasma lipids. We
      conclude that consumption of lowbush blueberries by rats confers protection to
      the brain against damage from ischemia, suggesting that inclusion of blueberries
      in the diet may improve ischemic stroke outcomes.

PMID- 12509073
TI  - A rapid effect of caffeinated beverages on two choice reaction time tasks.
AB  - Though consumers of tea and coffee can report feeling beneficial subjective
      effects of consumption virtually immediately, tests for objective effects of
      caffeine immediately post-consumption have been rare. Two experiments examined
      caffeine's ability to influence reaction time in choice reaction time tasks,
      using a dose of caffeine typical of a cup of tea or instant coffee, and testing
      at short post-consumption delays. Two groups of participants were given 60 mg of
      caffeine, after overnight abstinence, either in a hot tea drink, or a hot water
      drink. Two control groups also received hot tea or water, but without caffeine.
      In Experiment 1, participants were given a keypress task before the drink
      (baseline), immediately after the drink, and 40 min after the drink. In
      Experiment 2, a touch-screen test was given either 1, 14, or 27 min post
      consumption. Caffeine was found to reduce the effect of a distracter on reaction
      time in the keypress test and to reduce reaction time in a component of the touch
      screen task; however, in neither experiment were these effects significantly
      modulated by post-consumption delay length. Thus, the speed of caffeine's action
      on psychomotor performance was shown to be on the order of minutes.

PMID- 12509075
TI  - Veterinary surveillance: DEFRA puts forward its strategy.

PMID- 12509074
TI  - VMN/LHA functional inhibition in tumor-bearing rats suggests hypothalamic
      involvement in cancer anorexia.
AB  - Food intake is mainly controlled in the hypothalamus via a series of functionally
      related nuclei, including the ventromedial nucleus of hypothalamus (VMN) and the
      lateral hypothalamic area (LHA). Since food intake is the product of meal number
      and meal size, we investigated the role of the VMN and LHA in influencing these
      feeding indices and in mediating cancer anorexia in tumor-bearing (TB) rats, via
      temporarily inhibiting VMN or LHA. Adult male Fischer-344 rats (n = 23)
      inoculated with 106 MCA sarcoma cells were studied. When anorexia developed, rats
      were randomly assigned to stereotaxically located bilateral intra-VMN or intra
      LHA microinjections of the neuronal blocker colchicine (CX; n = 6 each group) or
      saline (n = 6 and n = 5, respectively). Non TB rats (NTB; n = 7) served as
      controls. Food intake and feeding indices were recorded by a computerized device.
      At onset of anorexia, a reduction of meal number occurred, leading to reduced
      food intake. After inhibition of VMN activity by CX, meal number significantly
      increased, so that food intake increased and almost normalized. In contrast,
      intra-LHA microinjection of either CX or saline resulted in reduction of meal
      size, leading to reduced food intake and death. Findings suggest that VMN and LHA
      influence meal number and meal size, respectively. Since cancer anorexia mainly
      results from an initial reduction of meal number and the inhibition of VMN led to
      an increase in meal number, the early effect of tumor growth on VMN activity may
      be an early step leading to reduced food intake.

PMID- 12509076
TI  - Evaluation of urinalysis as an aid in the diagnosis of equine grass sickness.
AB  - To determine whether urinalysis can aid the diagnosis of equine grass sickness,
      samples of urine from 15 horses with acute grass sickness, eight horses with
      subacute grass sickness, 17 co-grazing horses and 17 stabled control horses were
      analysed. The samples from all of the horses with grass sickness had a
      significantly higher specific gravity, higher protein and creatinine
      concentrations and a significantly lower pH; the samples from the horses with
      acute grass sickness also had significantly higher glucose concentrations. These
      differences may support a diagnosis of grass sickness but they are not
      pathognomonic for the disease.

PMID- 12509077
TI  - Expression of mRNA of chemokine receptor CXCR4 in feline mammary adenocarcinoma.
AB  - The expression of mRNA of the chemokine receptor CXCR4 in 65 surgically resected
      mammary adenocarcinomas from cats was investigated by in situ hybridisation. No
      expression of the receptor's mRNA was detectable in the mammary tissue of healthy
      cats, but it was expressed in areas adjacent to necrosis, surrounding blood
      vessels and cells infiltrating the lymphatics of 47 (72.3 per cent) of the 65
      samples. There was a significant relationship between lymphatic infiltration by
      neoplastic cells and the expression of the receptor's mRNA (P < 0.005), but there
      was no significant relationship between its expression and the one-year survival
      of the cats.

PMID- 12509078
TI  - Predisposition, subsequent fertility, and mortality of cows with uterine
      prolapse.

PMID- 12509079
TI  - Skeletal muscle rhabdomyosarcoma in a dog.

PMID- 12509080
TI  - Dermatitis associated with Dirofilaria repens microfilariae in a dog in Dubai.

PMID- 12509081
TI  - Structural changes in the testes and epididymides of bucks 16 weeks after
      bilateral vasectomy.

PMID- 12509082
TI  - H7N3 avian influenza in Italy.

PMID- 12509083
TI  - Competition Commission inquiry into POMs.

PMID- 12509084
TI  - Exemption orders.

PMID- 12509085
TI  - Decline in farm animal practice.

PMID- 12509086
TI  - Atherosclerosis in a red-crested turaco (Tauraco erythrolophus).

PMID- 12509087
TI  - Reducing death from cervical cancer examining the prevention paradigms.
AB  - The prevention of morbidity and mortality from cervical cancer will hinge upon
      our understanding of the epidemiology, the molecular basis, and natural history
      of the disease and its associated precursors. This article serves as an
      introduction and presents our current challenge to prevent or find all women at
      risk, and alter the course of disease to effect a regression or a cure.

PMID- 12509088
TI  - Paying for prevention standardizing the measurement of the value of health care
      interventions.
AB  - It is not clear if spending more on tests that enhance the accuracy of Pap smears
      would lead to a greater reduction in cancer incidence than if the money were
      spent to include a greater proportion of women in primary screening. The cost
      effectiveness of tests beyond the Pap smear has not been clearly demonstrated.
      There is the question of whether cervical cancer incidence can be decreased more
      by improving the tests for patients who are already screened or by improving
      access to the unscreened population. Cervical cancer screening represents only
      one of many public health issues competing for resources. Given that there are
      choices to be made, the optimal yardstick against which all resource-competing
      programs are measured should be marginal benefit versus marginal cost.

PMID- 12509089
TI  - Traditional management of invasive cervical cancer.
AB  - Cervical carcinoma is staged clinically by examination and simple radiological
      procedures. CT and MRI can, however, be used to guide management. Prognosis is
      best made by tumor size. depth of invasion, parametrial involvement, nodal
      status, LVSI, and histology. CIN III and CIS can be treated by ablative or
      excisional procedures. Hysterectomy should not be the primary treatment.
      Microinvasive (<3 mm) Stage IA cervical carcinoma can be treated conservatively
      with conization in patients who desire fertility, but the standard of care
      remains simple hysterectomy. Stages IB and IIA can be treated with either radical
      hysterectomy or radiation therapy dependent upon the patient's health and
      preference. Risk factors after radical hysterectomy (eg, bulky tumors, deep
      invasion, involved nodes or margins. LVSI) might warrant adjuvant radiation
      therapy. Chemoirradiation is the current standard of care for treatment for
      Stages IIB, III, and [VA. Some clinicians also use this modality in patients with
      Stage IB disease who are undergoing radiation as the primary treatment. Locally
      recurrent disease can be treated with either radiation (after radical
      hysterectomy) or pelvic exeteration (after primary radiation therapy).
      Exenteration in appropriately selected patients yields 5-year survival rates up
      to 82% with low complication rates. Many exenterations are aborted
      intraoperatively because of distant or unresectable disease, however. The
      incidence of glandular carcinoma of the cervix is rising, particularly in younger
      women. Cervical carcinoma detected during pregnancy requires the combined efforts
      of the gynecologic oncologist and the maternal-fetal medical specialist to
      determine the timing and method of treatment.

PMID- 12509090
TI  - New developments in the treatment of invasive cervical cancer.
AB  - Cervical cancer is a preventable disease that is curable when it is detected
      early. For advanced-stage cancer, the prognosis is worse. Over the years, much
      progress has been made in radiation therapy and in chemotherapy, but it took
      three decades for the arrival of concurrent chemoradiation therapy, which
      significantly improved the survival among women with advanced cervical cancer.
      This fact underscores the need and the importance for continuing efforts in
      clinical research. While current standards of therapy are being fine-tuned as
      more information is being gathered, great strides are being made in the areas of
      molecular and cancer biology. Novel treatments for cervical cancer appear to be
      imminent in the near future.

PMID- 12509091
TI  - In vitro conventional cytology historical strengths and current limitations.
AB  - Despite the fact that cervical cytology screening programs have dramatically
      reduced the prevalence of cervical cancer in the US, women continue to develop
      and die from the disease. The most important observation contributing to this
      failing is that 60% of women with invasive cancer have not had a Pap smear in the
      previous 5 years (or have never had one). The most clinically effective and cost
      effective approach to reducing the incidence of cervical cancer is to screen the
      unscreened population. Recent evidence has also noted that the sensitivity of
      conventional cytology is also much lower than was previously believed. Much
      recent investigation has been directed at identifying the reasons for this low
      sensitivity and identifying ways to improve it. Only by improving the sensitivity
      of cervical cancer screening and participation in screening programs can the
      prevalence, morbidity, and mortality from cervical cancer be further reduced.

PMID- 12509092
TI  - In vitro adjuncts to the pap smear.
AB  - The Pap smear has been recognized widely as the most effective cancer screening
      test in the history of medicine. It is widely believed that the use of this test
      has been responsible for the drastic reduction in the incidence and mortality of
      cervical cancer in the United States, Canada, and much of Western Europe in the
      last 50 years. Several adjuncts to the Pap smear including liquid based cytology,
      computer-assisted screening, human papilloma virus and molecular testing are
      discussed.

PMID- 12509093
TI  - Use of visual screening methods for cervical cancer screening.
AB  - This article has considered recent advances in visual screening methods. Devices
      that use electro-optical sensors offer great potential in various clinical roles,
      but considerable additional work is required to develop these devices and it is
      unlikely that they will come into widespread clinical use in the next 5 years. In
      contrast numerous studies, demonstrate that simple visual screening methods, such
      as DVI, have a sensitivity for the detection of women with biopsy-confirmed high
      grade SIL (CIN 2,3) and cancer that is equivalent to that of conventional
      cervical cytology. The primary disadvantage of the simple visual screening
      methods is poor specificity. These methods classify up to 30% of all women
      screened as being test positive and as a result new strategies toward managing
      DVI positive women must be developed before simple visual screening methods can
      be adopted for routine screening. Enhanced visual methods that use cervicography
      and speculoscopy may be more specific and improve detection of biopsy-confirmed
      SIL, but the added time and expense to perform either of these methodologies must
      be considered and justified. Currently numerous studies are evaluating the best
      strategies for incorporating visual screening methods into cervical cancer
      screening programs. In the near future we should be able to determine whether
      these approaches should be incorporated into routine clinical care.

PMID- 12509094
TI  - Efficient triage of the "screen-positive" at-risk patient.
AB  - At this time little, if any, of the vast knowledge base being generated by
      current research is available for practical application within screening
      programs, although the path is opening for the development of future
      methodologies that might someday lead to the successful eradication of cervical
      cancer. Current efforts to develop a vaccine against HPV are rapidly progressing
      and are promising. In the meantime, a better understanding and utilization of the
      technologies at hand will result in a successful, organized approach to the
      detection of early cervical cancer and its precursors [56]. The adoption of any
      new screening technologies must result in a documented reduction in the incidence
      of cervical cancer. Until then, colposcopy and HPV DNA testing when indicated
      appears to remain as the undisputed gold standard in the evaluation of the
      patient at risk.

PMID- 12509095
TI  - Management of precursor lesions of cervical carcinoma: history, host defense, and
      a survey of modalities.
AB  - Before the initiation of screening and treatment for cervical cancer precursors,
      approximately 3% to 4% of women were destined to eventually develop cervical
      cancer. During the last 50 years the rate of cervical cancer incidence and
      mortality has decreased by more than 75% primarily because of the widespread
      availability of cervical cytologic screening and of treatment for documented
      cervical precancer. Successful screening of the entire population and appropriate
      treatment of lesions could theoretically reduce this risk to one tenth of the
      risk of an unscreened population [7,28]. The relatively recent understanding of
      the etiology of cervical cancer precursor lesions and of the immune response to
      them has given new direction to management options that incorporate healthy
      habits and dietary measures as part of traditional ablative or excisional
      treatment options. As we look to the future we can expect that new markers that
      more specifically identify individuals at-risk for cervical precancer and cancer
      will be developed and take precedence in cervical screening. At the same time,
      treating the cause of these lesions, rather than the result, should provide less
      traumatic and more successful therapies. To this end, harnessing the immune
      system through immune response modifiers and HPV vaccines seems to be on the
      horizon, as do new chemopreventative approaches. Of all human cancers, only
      cervical cancer, once the second most common cancer among women, stands on the
      threshold of being virtually eliminated.

PMID- 12509096
TI  - Management of women with cervical cancer precursor lesions.
AB  - An understanding of the natural history of HPV-induced precancer and cancer, and
      of the immune response to HPV and to these lesions, has significantly changed the
      management of lower genital tract neoplasia. New management guidelines
      incorporate this understanding, providing a more rational approach to diagnosis
      and treatment. Understanding that low-grade HPV-induced lesions are not true
      cervical cancer precursor has fostered expectant management of women with these
      lesions; however, management approaches are still hampered by the inability to
      better predict who is at risk for high-grade intraepithelial neoplasia and cancer
      and who is not; this is particularly problematic in the expectant management of
      CIN 1. In addition, the decision whether or not to treat these low-grade lesions
      may depend on a number of complex factors that take into account the woman's
      preferences and reliability for follow-up, as well as a host of issues related to
      costs and the reliability of the original diagnosis and the tests used for follow
      up. Management options for high-grade cervical cancer precursor lesions are much
      more definitive, because the option of expectant management is given except in
      pregnancy and for adolescents with CIN 2. New markers that better predict which
      women with high-risk HPV are at highest risk for subsequent development of a true
      cervical cancer precursor lesion appear to be on the horizon and may make the
      management of low-grade lesions as clear as present guide lines for their high
      grade cousins. Until that time, understanding all the issues involved in
      expectant and in active management of cervical HPV-induced lesions will help
      provide women with the best care possible.

PMID- 12509097
TI  - Risk factors related to the development and mortality from invasive cervical
      cancer clinical utility and impact on prevention.
AB  - The focus of this article is to explore the various risk factors related to
      cervical cancer and the practical context in which they can be applied. The
      ability to link dinical outcomes (disease presence, persistence, progression, and
      recurrence) with antecedent risk factors is strengthened by a new understanding
      of the molecular mechanisms that are responsible for malignant transformation.

PMID- 12509098
TI  - Primary prevention of uterine cervix cancer: focus on vaccine history and current
      strategy.
AB  - Primary prevention of uterine cervix cancer spans the gamut of human
      papillomavirus vaccine development, dietary adjustment, chemoprevention, and risk
      reduction. Lifestyle and social behaviors impact on risk for cervical cancer.
      Before examining the growing body of molecular evidence, animal studies, and
      phase I clinical trials that suggest that a virus-based vaccine for cervical
      cancer may soon become a reality, one must reflect on what has gone before in the
      vaccine-based battle with viral disease.

PMID- 12509099
TI  - Genetic factors associated with development of cerebral malaria and fibrotic
      schistosomiasis.
AB  - Collaborative studies have identified some genetic factors contributing to the
      development of severe forms of malaria and schistosomiasis. In Thailand, the TNF
      alpha 5'-flanking region shows biallelic polymorphic sites at nucleotides -238, 
      308, -857, -863, and -1031, and seven alleles have been identified in patients
      from Myanmar. We found that the TNF promoter (TNFP)-D allele was significantly
      associated with cerebral malaria in populations from Karen (P < 0.0001, OR =
      124.86) and ethnic Burma (P < 0.0001, OR = 34.50). In China, we have identified
      two major genes related to the severity of liver fibrosis, one an HLA class II
      gene, and the other the IL-13 gene. The frequency of the HLA-DRB5*0101 allele and
      that of the IL-13 promoter A/A (IL-13P- A/A) genotype were elevated in fibrotic
      patients, although the two genes are located on different chromosomes,
      chromosomes 6p and 5q, respectively. Subjects with both genotypes had odds ratios
      (OR = 24.5) much higher than the sum of the ratios for each individual genotype
      (OR = 5.1, 95% Confidence Interval 1.3-24.7 for HLA-DRB5*0101, OR = 3.1 95% CI
      1.5 - 6.5 for IL-13P- A/A). That the effects of the two susceptibility markers
      are synergistic rather than additive, strongly suggests that the pathogenic Th2
      response directly influences the prognosis of post-schistosomal liver fibrosis.

PMID- 12509100
TI  - Ultrastructural localization of 28 kDa glutathione S-transferase in adult
      Clonorchis sinensis.
AB  - Glutathione S-transferase (28GST) with molecular mass of 28 kDa is an antioxidant
      enzyme abundant in Clonorchis sinensis. In adult C. sinensis, 28GST was localized
      in tegumental syncytium, cytons, parenchyma, and sperm tails examined by
      immunoelectron microscopy. C. sinensis 28GST was earlier found to neutralize
      bioreactive compounds and to be rich in eggs. Accordingly, it is suggested that
      28GST plays important roles in phase II defense system and physiological roles in
      worm fecundity of C. sinensis.

PMID- 12509101
TI  - A seroepidemiologic survey for human sparganosis in Gangweon-do.
AB  - Gangweon-do is known to be highly endemic area of sparganosis more than other
      provinces in Korea. A seroepidmiologic examination for the detection of anti
      Spirometra erinacei plerocercoid IgG in serum was carried out in normal
      inhabitants in Hongcheon-gun, Gangweon-do. Sere were tested by enzyme-linked
      immunosrobent assay (ELISA) for the anti-sparganum antibodies. Positive rate for
      anti-sparganum antibody in 719 adults was 3.3%. Data of the questionnaire for 24
      ELISA positive inhabitants revealed that 20 had a history of eating raw meat of
      snakes, 24 had a history of eating frogs, and 24 had a history of drinking stream
      water. Two positive cases had a past history of sparganosis. Two positive cases
      showed current symptoms of sparganosis. The data revealed that ELISA would be
      useful to find infected cases among normal inhabitants at sparganosis-endemic
      areas.

PMID- 12509102
TI  - Persistent infection with Strongyloides venezuelensis in the Mongolian gerbil
      (Meriones unguiculatus).
AB  - To examine the fate of Strongyloides venezuelensis. Mongolian gerbils (Meriones
      unguicalatus) were orally infected with 1,000 L3 larvae per animal. Altogether,
      50 gerbils divided into 5 groups of 10 each were monitored for a period of 570
      days to document the kinetics of faecal egg output, adults worm population,
      morphological development, fecundity, and hematological changes including
      peripheral blood eosinophilia. This study chronicled a life long parasitism of S.
      venezuelensis in the gerbil host, and showed that S. venezuelensis infection was
      quite stable throughout the course of infection and the worms maintained their
      normal development as evidenced by their body dimension. A progressive loss of
      body condition of the infected gerbils was observed as the level of infection
      advanced. However, no detectable pathological changes were observed in the
      gastrointestinal tract. The present findings indicate that an immunocompetent
      host, such as the Mongolian gerbil, can serve as a life long carrier model of S.
      venezuelensis if the worms are not expelled within 570 days after infection.

PMID- 12509103
TI  - A case of breast sparganosis.
AB  - A 29-year-old Korean woman visited the Department of Surgery in MizMedi Hospital
      with a palpable itching mass on the right breast that had existed for the past 7
      months. She had no history to eat either frogs or snakes, but had the history of
      drinking impure water. Sonography revealed a serpiginous hypoechoic tubular
      structure associated with partial fat necrosis in breast parenchymal layer and
      subcutaneous fat layer. It also revealed oval cystic lesions. At operation, an
      ivory white opaque ribbon-like worm that measured 16.5 cm in length and 0.5 cm in
      width was extracted. Anti-sparganum specific serum IgG level in the patient's
      serum (absorbance = 0.71), measured by ELISA, was found to be significantly
      higher than those of normal controls (cut off point = 0.21). Sonography and ELISA
      appear to be helpful to diagnose sparganosis. Breast sparganosis is rarely found
      throughout the world.

PMID- 12509104
TI  - Infection status of Clonorchis sinensis in residents of Hamyang-gun,
      Gyeongsangnam-do, Korea.
AB  - Oriental liver fluke (Clonorchis sinensis) infection was surveyed among residents
      of Hamyang-gun, Gyeongsangnam-do, Korea during the period of January 2001 to
      March 2002. Total 1,041 stool samples were collected from residents who visited
      Public Health Center and its branches in Hamyang-gun and examined using formalin
      ether sedimentation method. The overall egg positive rate was 16%, male showing
      higher positive rate (21%) than female (10%). The age group of 30 to 50 years had
      the highest egg positive rate of C. sinensis from 20% to 22%. The positive
      examinees were treated with praziquantel and educated individually to prevent
      reinfection. Egg positive rate in this area was decreased when compared with
      results recorded in the past, however, still remained more than 10%. This study
      suggests that periodic examination, treatment as well as education of residents
      should be continued and systematized.

PMID- 12509105
TI  - Cross-reactivity between sera from dogs experimentally infected with Dirofilaria
      immitis and crude extract of Toxocara canis.
AB  - This study was performed to investigate whethere there is cross-reactivity
      between Dirofilaria immitis and three intestinal nematodes of dogs. In ELISA, D.
      immitis-infected dog sera obtained at the 4th molting stage (9-11 weeks) and
      microfilaremic stage (25-30 weeks) were shown to be highly reactive with crude
      extract of T. canis. In immunoblotting, some antigenic fractions, 44, 57, 88, 100
      kDa of crude extract of T. canis, were found to be positive reaction with sera of
      dogs infected with D. immitis. However, little or no cross-reaction were observed
      between sera of D. immitis-infected dogs and crude extract antigen of T. vulpis
      or A. caninum. These result suggest that there are partial cross reaction between
      sera of D. immitis-infected dogs and the antigen of T. canis.

PMID- 12509106
TI  - Two human cases of tick bite caused by Ixodes nipponensis.
AB  - We report two human cases of tick bite. A 63-year-old male had a pruritic pea
      sized brownish nodule on the left popliteal area. Another 41-year-old male had an
      asymptomatic bean-sized black nodule in the pubic area. The ticks were identified
      as Ixodes nipponensis, which are the 18th and the 19th cases in Korea.

PMID- 12509107
TI  - Safety of medical diagnostic ultrasound.
AB  - The exemplary safety record of diagnostic ultrasound (DUS) is probably an
      important reason that it has become so widely used. Advances in technology and
      procedures promise to make it even more valuable. At the same time, some of these
      advances bring with them new situations where harm can occur unless they are
      given appropriate attention. Maintaining patient safety along with increasing
      benefits requires (1) a vigorous continuing research program for determining
      optimum operating conditions and (2) effective means for communicating guidance
      to users. In this article, a standard developed in the USA for displaying safety
      information is discussed.

PMID- 12509108
TI  - Routine ultrasound scanning in first trimester: what are the risks?
AB  - Acoustic exposure from modern ultrasonographic devices is capable of disturbing
      biological tissue to varying extent depending on the type of ultrasound
      examination and the particular tissue under investigation. There is no strong
      evidence that these biological effects present a serious health hazard, however,
      knowledge is incomplete, particularly from human studies. Although ultrasound
      induced heating can be significant in later pregnancy, it is unlikely that
      diagnostic ultrasound poses a significant thermal risk to the developing embryo
      when used according to published safety guidelines. Nevertheless, uncertainties
      remain, particularly for nonthermal effects in early pregnancy where shear
      stresses from radiation pressure may become an important factor. The likelihood
      of producing some biological effects can be enhanced by new procedures such as
      the use of gas encapsulated echo-contrast agents. The particular sensitivity of
      the embryo to physical damage together with uncertainties of both risk and
      benefit suggest that caution should be applied to the scanning of early first
      trimester uncomplicated pregnancy.

PMID- 12509109
TI  - MRI safety review.
AB  - Magnetic resonance is an extremely powerful imaging tool which does not expose
      patients to ionizing radiation. However, there are risks associated with the MR
      environment which all staff must be aware of and eliminate. The aim of this
      article is to highlight the well known and not so well known potentially adverse
      interactions. Although many safety investigations have been carried out at up to
      1.5T, the reader will be reminded that as many centres install magnets of 2.0T
      and above, much of the current safety literature cannot be simply extrapolated to
      these higher field strengths and further investigations will be required to
      reassure staff and patients of the limits of their safe use.

PMID- 12509110
TI  - CT scanning: a major source of radiation exposure.
AB  - CT scanning is a relatively high dose procedure that is becoming much more common
      worldwide. In the mid-1990s, CT scanning accounted for about 4% of procedures and
      about 40% of the collective dose in diagnostic radiology. With the advent of
      helical, fluoroscopic, and multi-slice techniques the dose per procedure has not
      diminished and the use of CT has increased even more. In large hospitals, CT
      scanning now accounts for about 15% of procedures and 75% of the diagnostic
      radiation dose received by patients. When multiple CT scans are conducted on the
      same patient, the absorbed doses are in the range at which small but
      statistically significant increases in cancer have been found in the atomic bomb
      survivors.

PMID- 12509111
TI  - How do radiographic techniques affect image quality and patient doses in CT?
AB  - The radiation dose received by patients who undergo CT examinations has become a
      subject of considerable interest. Adult effective doses for head CT examinations
      are of the order of 1 to 2 mSv, and for single body examinations, patient doses
      are typically between 4 and 6 mSv. These doses are high in comparison to most
      other types of radiological examinations that use ionizing radiation. Patient CT
      doses may also be compared with natural background (3 mSv/year), dose limits to
      members of the public (1 mSv/year), and the highest level of occupational
      exposure, which is about 5 mSv/year. The advent of multi-slice technology will
      serve to increase CT utilization, as well as individual doses for any given
      examination. Radiologists are responsible for medical radiation doses to their
      patients, and it is imperative that they understand the relationship between
      radiation dose and image quality. In this review, we address the impact that
      variations in radiographic techniques (ie, selected values of X-ray kVp and mAs)
      have on patient doses as well as the quality of the resultant CT images.

PMID- 12509112
TI  - Orbital, thyroid, and breast superficial radiation shielding for patients
      undergoing diagnostic CT.
AB  - Computed tomography (CT) now provides over 30% of all radiation received from
      medical imaging. Superficial radiosensitive organs, such as the thyroid, eyes,
      and breasts receive a greater proportion of this radiation because of increase
      scatter and the lack of overlying other tissues to partially absorb some of the
      dose. This article describes the use of bismuth radioprotective garments to
      shield these radiosensitive areas while preserving the overall quality of the
      diagnostic image.

PMID- 12509113
TI  - Radiation injuries after fluoroscopic procedures.
AB  - Fluoroscopically guided diagnostic and interventional procedures have become much
      more commonplace over the last decade. Current fluoroscopes are easily capable of
      producing dose rates in the range of 0.2 Gy (20 rads) per minute. The dose rate
      often changes dramatically with patient positioning and size. Most machines
      currently in use have no method to display approximate patient dose other than
      the rough surrogate of total fluoroscopy time. This does not include patient dose
      incurred during fluorography (serial imaging or cine runs), which can be
      considerably greater than dose during fluoroscopy. There have been over 100 cases
      of documented radiation skin and underlying tissue injury, a large portion of
      which resulted in dermal necrosis. The true number of injuries is undoubtedly
      much higher. The highest dose procedures are complex interventions such as those
      involving percutaneous angioplasties, stent placements, embolizations, and TIPS.
      In some cases skin doses have been in excess of 60 Gy (6000 rads). In many
      instances the procedures have been performed by physicians with little training
      in radiation effects, little appreciation of the radiation injuries that are
      possible or the strategies that could have been used to reduce both patient and
      staff doses. Almost all of the severe injuries that have occurred were avoidable.

PMID- 12509114
TI  - Hollow latex particles: synthesis and applications.
AB  - One of the major developments in emulsion polymerization over the last two
      decades has been the ability to make hollow latex particles. This has contributed
      many fundamental insights into the synthesis and the development of structure in
      particles. Hollow latex particles also enhance the performance of industrial
      coatings and potentially are useful in other technologies such as
      microencapsulation and controlled release. Ever since the publication of the
      initial process patents describing these particles, there has been a global R&D
      effort to extend the synthetic techniques and applications. One prominent
      synthetic approach to hollow particles is based on osmotic swelling. This
      dominates the literature, and usually starts with the synthesis of a structured
      latex particle containing an ionizable core that is subsequently expanded with
      the addition of base. Fundamental to this approach are a sophisticated control of
      transport phenomena, chemical reactivity within the particle, and the
      thermoplastic properties of the polymer shell. Hydrocarbon encapsulation
      technology has also been employed to make hollow latex particles. One approach
      involves a dispersed ternary system that balances transport, conversion kinetics,
      and phase separation variables to achieve the hollow morphology. Other
      techniques, including the use of blowing agents, are also present in the
      literature. The broad range of approaches that affords particles with a hollow
      structure demonstrates the unique flexibility of the emulsion polymerization
      process.

PMID- 12509116
TI  - Preparation of a stable double emulsion (W1/O/W2): role of the interfacial films
      on the stability of the system.
AB  - This paper presents new protocols enabling preparation of W1/O/W2 double
      emulsions: one, using soybean oil as the O phase, that yields edible emulsions
      with industrial applications, and a second that yields emulsions with a
      previously unattainable concentration 15% (w/w) of surfactants in the external
      phase (the 15% target was chosen to meet the typical industry standard).
      Preparation of a stable W1/O emulsion was found to be critical for the stability
      of the system as a whole. Of the various low HLB primary surfactants tested, only
      cethyl dimethicone copolyol (Abil EM90), A-B-A block copolymer (Arlacel P135),
      and polyglycerol ester of ricinoleic acid (Grinstead PGR-90) yielded a stable W/O
      emulsion. Investigation of the surface properties of those surfactants using the
      monolayer technique found two significant similarities: (1) stable, compressible,
      and reversibly expandable monolayers; and (2) high elasticity and surface
      potential. The high degree of elasticity of the interfacial film between W1 and O
      makes it highly resilient under stress; its failure to break contributes to the
      stability of the emulsion. The high surface potential values observed suggest
      that the surfactant molecules lie flat at the O/W interfaces. In particular, in
      the case of PGR-90, the hydroxyl (-OH) groups on the fatty acid chains serve as
      anchors at the O/W interfaces and are responsible for the high surface potential.
      The long-term stability of the double emulsion requires a balance between the
      Laplace and osmotic pressures (between W1 droplets in O and between W1 droplets
      and the external aqueous phase W2). The presence of a thickener in the outer
      phase is necessary in order to reach a viscosity ratio (preferably approximately
      1) between the W1/O and W2 phases, allowing dispersion of the viscous primary
      emulsion into the W2 aqueous phase. The thickener, which also serves as a
      dispersant and consequently prevents phase separation due to its thixotropic
      properties, must be compatible with the surfactants. Finally, the interactions
      between the low and high HLB emulsifiers at the O/W2 interface should not
      destabilize the films. It was observed that such destructive interaction for the
      system could be prevented by the use of two high HLB surfactants in the outer
      aqueous phase: an amphoteric surfactant, Betaine, and an anionic surfactant,
      sodium lauryl ether sulfate. The combination of such pairs of surfactants was
      found to contribute to the films' stability.

PMID- 12509115
TI  - Synthesis and general properties of silated-hydroxypropyl methylcellulose in
      prospect of biomedical use.
AB  - Synthesis of grafting silane on a hydro soluble cellulose ether (HPMC) was
      described. In alkaline medium, this derivate is under gel form. With a decrease
      of the pH, a self-hardening occurs due to the silanol condensation. For potential
      biomedical use, we described the silated-HPMC synthesis, the gel behavior after
      steam sterilization and the parameters of the silanol condensation i.e. pH,
      silane percentage and temperature. Minimum kinetic of the condensation was
      observed for pH between 5.5 and 6.5. So temperature catalyzed the reaction and
      the self-hardening speed was increased by silane percentage.

PMID- 12509117
TI  - The significance of the difference in the point of zero charge between rutile and
      anatase.
AB  - The points of zero charge (PZC) of titanium dioxide reported in the literature
      range from 2 to 8.9. A set of 138 PZC of titanium dioxide was used to explore the
      effect of the crystalline structure on the PZC. The average and median PZC at pH
      5.6 and 5.8, respectively, was found when the entire data set was taken into
      account. The PZC of anatase (31 entries, average and median 5.9 and 6,
      respectively) is slightly higher than that of rutile (49 entries, average and
      median 5.4 and 5.5, respectively), and the difference between the polymorphs
      corresponds to half of a standard deviation in each set of PZC.

PMID- 12509118
TI  - Experimenting with new paradigms for medical education and the emergence of a
      distance learning degree using the internet: teaching evidence-based medicine.
AB  - This paper is focused on designing and developing a teaching environment
      associated with an introductory course in evidence-based medicine designed for
      undergraduates. Attempting to break away from the traditional educational model
      based on acquisition of factual knowledge, we developed a software tool centred
      on content management, student assessment and feedback. We ran this course on an
      educational website, using chat rooms and electronic mail for trainer-trainee
      communication over one academic year. The website served as a repository for
      knowledge and information and presented freestanding web-based interactive study
      modules and a non-interactive degree course. Trainers and trainees responded
      favourably to the computer applications and the Internet. This project
      demonstrated the feasibility of computer-aided learning and the advantages of
      distance teaching over the Internet.

PMID- 12509119
TI  - Health-related services on the internet.
AB  - The primary objective of this study is to evaluate a sample of health-related
      services available on the internet. In addition, types of new services and
      service qualities that may be required in the future were estimated. A registered
      nurse using a questionnaire containing items about usability, quality, and other
      characteristics related to the subject carried out an evaluation of 100 health
      related internet sites, and the results were processed to determine average
      qualities and graphical presentations for the studied parameters. The services
      studied differed greatly from each other both in terms of content and quality. A
      general observation was that sites of larger organizations were, typically, both
      in terms of presentation and content, more sophisticated than sites of smaller
      producers. A typical characteristic was the superficiality of the information
      presented. In conclusion, the internet is an emerging medium for health-related
      information, and standards for the production and presentation of health content
      for the internet are still in development. However, even at this early stage, the
      internet represents a valuable source of information for those in need of health
      related information for both health care professionals and consumers.

PMID- 12509120
TI  - Effect of display modality on spatial accuracy of orthopaedic surgery pre
      operative planning applications.
AB  - Graphical representation of a patient's anatomy is fairly similar in the majority
      of orthopaedic surgery planning programs. The position of implantable devices is
      usually established using a three-pane window showing 2D cross sections of the CT
      data set taken on three user-selectable orthogonal planes. In some cases this
      orthogonal-plane representation is replaced or extended by interactive 3D
      visualization, obtained using surface rendering techniques. These ways to
      represent the CT data come naturally and easily to the programmer. However, the
      efficacy of these display strategies is questionable. The present study aims to
      assess if the display modality used to visualize CT data affects the inherent
      spatial accuracy achievable in a surgical planning application. A group of users
      was asked to perform repeatedly a specific planning task using various display
      interfaces to the same underlying software application. The planning task was
      designed to allow an assessment of the accuracy with which each user was able to
      position the prosthetic component. A specialized interface, called multimodal
      display, presented a peak error of 0.45 mm and 0.95 deg, significantly lower than
      the 2.4 mm and 4 deg for the othogonal slices interface, and the 3.8 mm and 16.7
      deg for the 3D-rendering interface. The results of this study indicate an
      important effect of the type of visualization modality used to represent CT data
      on final accuracy of the planning operation.

PMID- 12509121
TI  - Quality of data on subsequent events in a routine Medical Birth Register.
AB  - BACKGROUND: The maintenance of health registers has become routine. The main
      prerequisite for their use is that registers be complete and that their contents
      correspond to reality. METHODS: Data on all primiparous women who gave birth
      between 1987 and 1989 (N=73009) and on their second (N=55388) and third births
      (N=22904) in the 1987-1998 period were retrieved from the Finnish Medical Birth
      Register (MBR). The consistency of the MBR data on reproductive history and on
      previous Caesarean section was investigated by comparing the records on
      subsequent births. MAIN RESULTS: In total 98.5% of the information on
      reproductive history corresponded with the previous data in the MBR. Data quality
      decreased over time and with increasing parity. There were problems with the
      registration of rare cases, e.g. several extrauterine pregnancies or stillbirths.
      The quality deteriorated in the late 1990s, because no data on previous induced
      abortions and extrauterine pregnancies were collected between 1991 and 1995. The
      quality of data on previous Caesarean section was poor in 1987-1990, a period
      when the data were collected by using ICD-9 codes, but the quality improved after
      the introduction of a check-box format in 1991. CONCLUSIONS: Changes in question
      formats may change the quality of register data significantly. Check-boxes seem
      to improve quality compared to open-ended questions. The data on reproductive
      history and previous Caesarean sections could be combined routinely to improve
      the quality of the MBR.

PMID- 12509122
TI  - Neural network identification of high-risk suicide patients.
AB  - BACKGROUND: A history of medically serious suicide attempts (MSSA) has been
      considered a major risk factor for suicide. Backpropagation (BP) neural networks
      (NN) successfully detected patient files of patients who had committed MSSA but
      failed to identify MSSA patients when trained with data collected during face-to
      face interviews. PRIMARY OBJECTIVES: To develop an expert support system for the
      detection of suicide risk in patients with major psychiatric disorders using
      fuzzy adaptive learning control networks (FALCON) and BP enhanced with fuzzy
      logic neural networks. METHODS AND PROCEDURES: We used four types of input sets:
      (a) the most significant variables as defined by Garson's calculation of trained
      BP; (b) variables identified by logistic regression; (c) variables considered
      significant by experienced clinicians; or (d) the variables considered definitive
      by the computer programmer. In addition, the complete set of 59 input variables
      was used. The target variable was the existence of prior MSSA. EXPERIMENTAL
      INTERVENTIONS: Four training trials were performed with each input set (75% of
      the data was used for training and 25% for testing). Data was collected from 197
      (50 MSSA, 147 non-MSSA) patients hospitalized at Sha'ar Menashe Mental Health
      Centre. MAIN OUTCOMES AND RESULTS: BP enhanced with fuzzy logic achieved the most
      accurate results with the three variables chosen by the programmer (mean +/- SD;
      sensitivity=97% +/- 3.4%, specificity=69.2% +/- 6.9%), and FALCON trained with 15
      variables chosen by an expert clinician obtained the highest sensitivity and
      specificity (mean +/- SD; sensitivity=94% +/- 6.9%, specificity=69% +/- 6.9%).
      CONCLUSIONS: A combined system of BP enhanced with fuzzy logic and FALCON may
      improve the detection rate of MSSA patients during patient interviews. A
      prospective validation study testing a combined system across 1, 2 and 5-year
      spans may provide a reliable instrument to aid in the detection of suicide prone
      psychiatric patients.

PMID- 12509123
TI  - Use of an artificial neural network to differentiate between ECGs with IRBBB
      patterns of atrial septal defect and healthy subjects.
AB  - Atrial septal defect (ASD) is one of the most commonly recognized congenital
      cardiac anomalies in adults, but its diagnosis is easily missed because about
      half of the patients are asymptomatic early in life. Although an
      electrocardiogram (ECC) diagnosis with an incomplete right bundle branch block
      (IRBBB) pattern is of major importance for this disease, an RSR' complex similar
      to an IRBBB pattern is also found in some healthy individuals. A feed-forward
      artificial neural network was constructed to distinguish between ASD and healthy
      subjects using 12-lead ECGs with IRBBB. A total of 106 clinically validated
      subjects, including 58 with ASD and 48 healthy subjects were used in this study.
      QRS and T wave measurements from I, II, and all precordial leads were used as the
      input parameters to a back propagation network. The leave-one-out method revealed
      that in the test data (106 cases), the overall accuracy, sensitivity and
      specificity of the artificial neural network were 91.5, 91.4, and 91.7%,
      respectively. This study demonstrates that the neural network technique may offer
      higher accuracy than computerized ECG diagnosis of IRBBB from the viewpoint of
      ASD.

PMID- 12509124
TI  - Appropriate medical data categorization for data mining classification
      techniques.
AB  - Some data mining (DM) methods, or software tools, require normalized data, others
      rely on categorized data, and some can accommodate multiple data scales. Each DM
      technique has a specific background theory; therefore, different results are
      expected when applying multiple methods. The purpose of this study is to find the
      data format appropriate for each DM classification technique for wider
      applications, and efficiently to obtain trustworthy results. Considering the
      nature of medical data, categorical variables are sometimes useful for making
      decisions and can make it easier to extrapolate knowledge. In this study, three
      mathematical data categorization methods (Fusinter, minimum description length
      principle [MDLPC] and Chi-merge) were applied to accommodate five data mining
      classification techniques (statistics discriminant analysis, supervised
      classification with Neural Networks, Decision trees, Genetic supervised
      clustering and Bayesian classification [probability neural networks; PNN]) using
      a heart disease database with four types of data (continuous data, binary data,
      nominal data, and ordinal data). Compared with original or normalized data, data
      categorized by the MDLPC categorization method was found to perform better in
      most of the DM classification techniques used in this study. Categorical data is
      good for most DM classification techniques (e.g. classification of disease and
      non-disease groups) and is relatively easy to use for extracting medical
      knowledge.

PMID- 12509125
TI  - Developmental roles and clinical significance of hedgehog signaling.
AB  - Cell signaling plays a key role in the development of all multicellular
      organisms. Numerous studies have established the importance of Hedgehog signaling
      in a wide variety of regulatory functions during the development of vertebrate
      and invertebrate organisms. Several reviews have discussed the signaling
      components in this pathway, their various interactions, and some of the general
      principles that govern Hedgehog signaling mechanisms. This review focuses on the
      developing systems themselves, providing a comprehensive survey of the role of
      Hedgehog signaling in each of these. We also discuss the increasing significance
      of Hedgehog signaling in the clinical setting.

PMID- 12509126
TI  - Genomic imprinting: could the chromatin structure be the driving force?
AB  - Genomic imprinting is traditionally defined as an epigenetic process leading to
      parental origin-dependent monoallelic expression of some genes. The current
      paradigm considers this unusual expression mode as the biological raison d etre
      of imprinting. The present chapter proposes a critical review of our ideas about
      genomic imprinting in light of more recent investigatory progress. Many
      observations are difficult to explain on the basis of the current paradigm.
      Studies of allelic expression of many imprinted genes and other characteristics
      of chromatin domains containing clustered imprinted genes, such as replication
      and chromatin structure, revealed an unexpectedly complex situation that
      challenged the role of genomic imprinting as a mechanism of transcriptional
      regulation. The emerging picture is that parental imprinting is a feature of
      large chromatin domains with their own domain-wide characteristics. The primary
      biological function of imprinting may reside in the differential chromatin
      structure of the parental chromosomal regions and not in the monoallelic
      expression of some of the genes contained within them.

PMID- 12509127
TI  - Patterning the sea urchin embryo: gene regulatory networks, signaling pathways,
      and cellular interactions.
AB  - We discuss steps in the specification of major tissue territories of the sea
      urchin embryo that occur between fertilization and hatching blastula stage and
      the cellular interactions required to coordinate morphogenetic processes that
      begin after hatching. We review evidence that has led to new ideas about how this
      embryo is initially patterned: (1) Specification of most of the tissue
      territories is not direct, but proceeds gradually by progressive subdivision of
      broad, maternally specified domains that depend on opposing gradients in the
      ratios of animalizing transcription factors (ATFs) and vegetalizing (beta
      catenin) transcription factors; (2) the range of maternal nuclear beta-catenin
      extends further than previously proposed, that is, into the animal hemisphere,
      where it programs many cells to adopt early aboral ectoderm characteristics; (3)
      cells at the extreme animal pole constitute a unique ectoderm region, lacking
      nuclear beta-catenin; (4) the pluripotential mesendoderm is created by the
      combined outputs of ATFs and nuclear beta-catenin, which initially overlap in the
      macromeres, and by an undefined early micromere signal; (5) later micromere
      signals, which activate Notch and Wnt pathways, subdivide mesendoderm into
      secondary mesenchyme and endoderm; and (6) oral ectoderm specification requires
      reprogramming early aboral ectoderm at about the hatching blastula stage.
      Morphogenetic processes that follow initial fate specification depend critically
      on continued interactions among cells in different territories. As illustrations,
      we discuss the regulation of (1) the ectoderm/endoderm boundary, (2) mesenchyme
      positioning and skeletal growth, (3) ciliated band formation, and (4) several
      suppressive interactions operating late in embryogenesis to limit the fates of
      multipotent cells.

PMID- 12509128
TI  - Teasing apart TSE models.

PMID- 12509130
TI  - Plant immunity: a complex interface between host and pathogen.

PMID- 12509129
TI  - Transgenesis applied to transmissible spongiform encephalopathies.
AB  - Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative
      disorders present in various mammals. TSEs have been studies intensively, even
      more so following the BSE crisis and the subsequent threat of a human nvCJD
      epidemic. In the 'protein-only' hypothesis, the infectious agent, called prion,
      is assumed to be a misfolded host protein. Transgenesis has mainly been applied
      to study the role of this protein, its structure-function relationship with
      respect to its pathogenic properties and to assess the genetic origin of the well
      recognised species barrier effect. This approach has somewhat supplemented the
      lack of in vitro models. This review will try to summarise the impressive work
      that has been done in this field. Although many questions remain unanswered,
      transgenic experiments have and will still improve our knowledge on this disease
      and might help us to develop critically needed therapeutic approaches.

PMID- 12509132
TI  - Inducible diabetes and transgene expression in a single mouse: a tool to
      elucidate autoimmune mechanisms.

PMID- 12509131
TI  - Resistance and susceptibility of plants to fungal pathogens.
AB  - Plants are under continuous threat of infection by pathogens endowed with diverse
      strategies to colonize their host. Comprehensive biochemical and genetic
      approaches are now starting to reveal the complex signaling pathways that mediate
      plant disease resistance. Initiation of defense signaling often involves specific
      recognition of invading pathogens by the products of specialized host resistance
      (R) genes. Potential resistance signaling components have been identified by
      mutational analyses to be required for specific resistance in the model
      Arabidopsis and some crop species. Strikingly, many of the components share
      similarity to that of innate immune systems in animals. Evidence is also
      accumulating that plant pathogens have a number of ways to evade host defenses
      during the early stages of infection, similar to animal pathogens. These
      strategies are becoming much better understood in a number of plant-pathogen
      interactions. In this review, we focus on the current knowledge of host factors
      that control plant resistance and susceptibility to fungal pathogens. The
      knowledge accumulated in these studies will serve a fundamental basis for
      combating diseases in strategic molecular agriculture.

PMID- 12509133
TI  - Transgenic animal models for type 1 diabetes: linking a tetracycline-inducible
      promoter with a virus-inducible mouse model.
AB  - Autoimmunity is thought to emerge as a consequence of genetic predispositions and
      environmental tiggering factors. Often the etiology and the mechanisms involved
      in the autoaggressive destruction of self-components are rather complex and in
      many cases poorly understood. Chemokines and cytokines are central mediators of
      inflammatory processes that are involved in initiation and progression of
      autoimmunity. Many animal models for human autoimmune diseases use transgenic
      technology to express chemokines and/or cytokines in an organ or tissue specific
      manner. However, most of these model systems express the transgene irreversibly
      without considering the time of expression as a very important parameter. Here,
      we review experiences that were made from using a tetracycline-inducible promotor
      system (tTA-system) to express TNFalpha at various times during an ongoing
      autoimmune process, such as the destruction of pancreatic beta-cells in a mouse
      model for human type 1 diabetes.

PMID- 12509134
TI  - Future prospects for developing disease resistant plants.

PMID- 12509135
TI  - Engineering pathogen resistance in crop plants.
AB  - As the world population continues to increase, food supplies must also grow to
      meet nutritional requirements. One means of ensuring the stability and plentitude
      of the food supply is to mitigate crop loss caused by plant pathogens. Strategies
      for combating disease include traditional technologies such as plant breeding and
      chemical applications; current technologies such as generating transgenic plants
      that express components of known defense signaling pathways; and the adaptation
      of newer technologies such as RNA silencing of pathogen and plant transcripts.
      Breeding has been used to pyramid resistance (R) genes into many different plants
      including rice. Chemical strategies include application of salicylic acid (SA)
      analogs to stimulate systemic acquired resistance (SAR) responses. Genetic
      screens in Arabidopsis have identified genes controlling SAR and these genes have
      been manipulated and used to engineer crop plants. The diseases caused by plant
      viruses are being thwarted through the initiation of endogenous RNA silencing
      mechanisms. Many of these strategies show great promise, some limitations, and
      exciting opportunities to develop many new tools for combating plant pests.

PMID- 12509136
TI  - The search for breast cancer therapies--the value of genetically engineered mice.

PMID- 12509138
TI  - Validation of transgenic mammary cancer models: goals of the NCI Mouse Models of
      Human Cancer Consortium and the mammary cancer CD-ROM.

PMID- 12509137
TI  - Pre-clinical applications of transgenic mouse mammary cancer models.
AB  - Breast cancer is a leading cause of cancer morbidity and mortality. Given that
      the majority of human breast cancers appear to be due to non-genetic factors,
      identifying agents and mechanisms of prevention is key to lowering the incidence
      of cancer. Genetically engineered mouse models of mammary cancer have been
      important in elucidating molecular pathways and signaling events associated with
      the initiation, promotion, and the progression of cancer. Since several
      transgenic mammary models of human breast cancer progress through well-defined
      cancer stages, they are useful pre-clinical systems to test the efficacy of
      chemopreventive and chemotherapeutic agents. This review outlines several
      oncogenic pathways through which mammary cancer can be induced in transgenic
      models and describes several types of preventive and therapeutic agents that have
      been tested in transgenic models of mammary cancer. The effectiveness of farnesyl
      inhibitors, aromatase inhibitors, differentiating agents, polyamine inhibitors,
      anti-angiogenic inhibitors, and immunotherapeutic compounds including vaccines
      have been evaluated in reducing mammary cancer and tumor progression in
      transgenic models.

PMID- 12509139
TI  - Gene silencing mechanisms illuminate new pathways of disease resistance.

PMID- 12509141
TI  - NIR to UV absorption spectra and the optical constants of phthalocyanines in
      glassy medium.
AB  - Optical absorption studies of phthalocyanines (Pc-s) in borate glass matrix have
      been reported for the first time. Measurements have been done corresponding to
      photon energies between 1.1 and 6.2 eV for free base, manganese, iron, nickel,
      molybdenum, cobalt and copper phthalocyanines. Several new discrete transitions
      are observed in the UV-vis region of the spectra in addition to a strong
      continuum component of absorption in the IR region. Values of some of the
      important optical constants viz. absorption coefficient (alpha), molar extinction
      coefficient (epsilon), absorption cross-section (sigma(a)), band width (delta
      lambda), electric dipole strength (q2) and oscillator strength (f) for the
      relevant electronic transitions are also presented. All the data reported for Pc
      s in the new matrix have been compared with those corresponding to solution,
      vapor and thin film media.

PMID- 12509142
TI  - A numerical test of analytical methods for reduction of IR and MW spectra of NaCl
      chi1sigma+ to parameters of radial functions.
AB  - Two methods for direct inversion of IR and MW spectra of diatomic molecules--a
      deformational self-consistent procedure (DS-cP) and a computer program RADIATOM
      based on hypervirial perturbation theory are tested numerically. The test
      calculations for NaCl chi1sigma+ confirm that the RADIATOM program does not
      produce sufficiently accurate radial parameters and energy term values for their
      export to other utilities employed in the spectral analysis of diatomic systems.

PMID- 12509140
TI  - Gene silencing-based disease resistance.
AB  - The definition of a disease is fundamentally difficult, even if one considers
      only genetically based diseases. In its broadest sense, disease can be defined as
      any deviation from the norm that results in a physiological disadvantage. Natural
      selection ensures that the norm for any given species is constantly changing. In
      addition, some disadvantages are latent and might only manifest under certain
      environmental conditions. Conversely, an apparent disadvantage can carry a
      benefit, for example, the disease sickle-cell anemia that is an advantage in
      malarial areas. Because of the difficulties in giving disease a precise
      definition, in this review, gene silencing-based disease resistance will be
      restricted to the description of gene inactivation processes that contribute to
      maintain the physical fitness of an organism. In this sense, we are concerned
      with the elimination of invasive nucleic acid expressing. In numerous organisms,
      a variety of severe diseases are caused by the attack of invasive nucleic acids
      such as viruses and retroviral or transposable elements. Organisms have developed
      diverse mechanisms to defend themselves against such attack that include immune
      responses and apoptosis. Fungi, plants, invertebrates and vertebrates also enlist
      gene silencing systems to counteract the harmful effects of invasive nucleic
      acids. In particular, plants that lack interferon and immune responses have
      established efficient transcriptional and post-transcriptional gene silencing
      systems. In this review, we describe how plants defend against invasive nucleic
      acids and focus on the continual evolutionary battle between plants and viruses.
      In addition, the importance of controlling transposon activity is outlined.
      Finally, gene silencing-related mechanisms of genomic imprinting and X-chromosome
      inactivation are discussed in the context of disease resistance.

PMID- 12509143
TI  - Selective complex formation of some chromogenic calix[4]arene derivatives
      detected by Fourier transform infrared spectroscopy 1. Solution experiments.
AB  - A calix[4]arene derivative containing ethoxycarbonylmethoxy groups in the
      coordination sphere and an iminopyridinium indicator group was studied by FT-IR
      spectroscopy in acetonitrile solution. The characteristic changes of v(C=O)
      stretching vibration offered an opportunity for the improvement on selectivity of
      the ion recognition process of this ligand. The shift of the carbonyl stretching
      vibration band depended on complex formation as well as on the equilibrium
      constants of complex formation. In the case of sodium complex, a well-defined
      isobestic point was detected in the v(C=O) region while altering the sodium
      concentration. The affinity of thallium(III) to form complex with calixarene 1
      was found comparable with those of lithium, sodium or calcium. The complex was
      found to be an M2L type supramolecule, whereas one molecule of triethylamine was
      necessary for the formation of each complex.

PMID- 12509144
TI  - Infrared spectra of proton transfer complexes of the cycleanine alkaloid in solid
      state.
AB  - Proton transfer complexes obtained between the cycleanine alkaloid and hydrogen
      chloride, hydrogen bromide and nitric acids have been investigated by infrared
      spectroscopic technique between 4000 and 400 cm(-1) in KBr. The vibrational
      perturbations brought about by proton transfer complex formation, discussed in
      terms of preferred site of interaction, show that the proton of the inorganic
      acids is transferred to cycleanine through one of its N sites.

PMID- 12509145
TI  - The infrared fundamental intensities and polar tensor of CH3NC.
AB  - The molecular force field and polar tensor of methyl isocyanide have been
      determined from its gas phase vibrational frequencies and infrared intensities.
      Quantum chemical results from MP2(FC), B3LYP and quadratic configuration
      interaction calculation including single and double substitutions procedures
      using a 6-311 + +G(3d,3p) basis set have been used to determine the signs of the
      dipole moment derivatives with respect to the normal coordinates as well as
      estimate individual fundamental intensities of the overlapped v1-v5 and v3-v6
      band systems. Principal component graphical representations of the A1 and E
      symmetry polar tensor elements were useful in determining preferred sets of
      tensor elements. The mean dipole moment derivative (GAPT charge) of the methyl
      carbon in CH3NC, 0.347 e, is between the corresponding values in CH3CN, 0.110 e,
      and CH3F, 0.541 e. The mean dipole moment derivatives obtained here indicate the
      correct 1s methyl carbon ionization energy as 293.35 eV which is 0.98 eV higher
      than the corresponding ionization energy of the terminal atom.

PMID- 12509146
TI  - Vibrational characterization of the peptide bond.
AB  - This article describes the complete vibrational analysis of N,N'-dimethyloxamide,
      CH3HNCOCONHCH3, on basis of the infrared and Raman spectra of four isotopes (H,
      D, CH3, CD3). Force field calculations on the monomers and multimers (n = 5)
      combined with solid state spectra in the -196 to +100 degrees C temperature range
      have been used to obtain a better understanding of the influence of hydrogen
      bonding on the typical amide fundamentals. The cooperative effect in de series
      monomer --> multimers --> solid state at decreasing temperatures has been
      demonstrated. Nine typical so-called 'amide bands' have been further
      characterized and special attention has been given to the Amide IV mode. The
      influence of the CH and CD vibrations on the amide fundamentals, has been studied
      by comparison with the calculated and experimental fundamentals and P.E.D. values
      of the CH3 and CD3 isotopes. The most important amide bands have further been
      assigned in X-CONHCH3 molecules where X = methyl, amide, thioamide, ester, salt,
      cyanide and acid functional groups.

PMID- 12509147
TI  - The lowest excited triplet (T1) energies of p-methoxybenzaldehyde and p
      cyanobenzaldehyde vapors estimated from the temperature dependence of the T2(n,
      pi*) phosphorescence and the S1(n, pi*) fluorescence spectra.
AB  - Invisible energy levels of the T1(pi, pi*) state of p-methoxybenzaldehyde
      (anisaldehyde) and p-cyanobenzaldehyde vapors have been estimated through the
      temperature dependence of the T2(n, pi*) --> S0 phosphorescence and the S1(n,
      pi*) --> S0 delayed fluorescence spectra. It is shown that the T1(pi, pi*) levels
      are located at 900 +/- 100 and 300 +/- 100 cm(-1) below the T2(n, pi*) levels,
      respectively, for p-methoxybenzaldehyde and p-cyanobenzaldehyde vapors. The
      estimated T1 energy levels are in good agreement with the phosphorescence origins
      in rigid glass at 77 K.

PMID- 12509148
TI  - Electrochemical and microsomal production of free radicals from 1,2,5-oxadiazole
      N-oxide as potential antiprotozoal drugs.
AB  - The electron spin resonance (ESR) spectra of free radicals obtained by
      electrolytic or microsomal reduction of several potential antiprotozoal 1,2,5
      oxadiazoles were characterized and analyzed. Ab initio molecular orbital
      calculations were performed to obtain the optimized geometries and the
      theoretical hyperfine constant was carried out using ZINDO semiempirical
      methodology. Density functional theory was used to rationalize the reduction
      potentials of these compounds.

PMID- 12509149
TI  - Rotamerism and electronic spectra of aza-derivatives of stilbene and
      diphenylbutadiene. A combined experimental and theoretical study.
AB  - The experimental results on the rotameric equilibrium and electronic spectra of
      aza-derivatives of trans-stilbene and 1,4-diphenylbutadiene, have been
      rationalized by a theoretical study which combines simple ab initio calculations
      of molecular energies for the ground state with a theoretical analysis of the
      splitting of the conjugation band developed at CS INDO CI level. All results
      indicate that the stable conformer of each ortho aza-derivative is that
      corresponding to A species. As suggested by the 1H-NMR experiments, the ab initio
      geometry of ZE-2-pyridylphenylbutadiene is consistent with the presence of the
      N.H intramolecular hydrogen bond. As regards the Franck-Condon excited states of
      aza-derivatives, our theoretical results show that the first singlet excited
      state has (piH, piL*) character in all compounds except for E-4,4'
      dipyridylethene, where S1 has (n, pi*) character in non-polar solvent. In this
      last compound, the theoretical study of solvatochromism indicates a crossing
      between the 1(n, piL*) and 1(piH, piL*) states which occurs in solvents of high
      polarity. The inclusion of the most important doubly- and triply-excited
      configurations in the CI calculations shows that the 1A(g)- excited state is
      above the spectral region analyzed.

PMID- 12509150
TI  - Raman and infrared spectral study of meso-sulfonatophenyl substituted porphyrins
      (TPPSn, n = 1, 2A, 2O, 3, 4).
AB  - Raman and IR spectra of the free base p-sulfonatophenyl and phenyl meso
      substituted porphyrins [5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4);
      5,10,15-tris(4-sulfonatophenyl)-20-phenyl-porphyrin (TPPS3); 5,10-bis(4
      sulfonatophenyl)-15,20-diphenylporphyrin (TPPS2A); 5,15-bis(4-sulfonatophenyl)
      10,20-diphenylporphyrin (TPPS2O); and 5-(4-sulfonatophenyl)-10, 15,20
      trisphenylporphyrin (TPPS1)] and their N-diprotonated derivatives (porphyrin
      diacids) were studied. The Raman spectra of the deuterated analogues of these
      porphyrins, in which the central hydrogen atoms were substituted with deuterium,
      were also measured. The observed vibrational bands were assigned on the basis of
      the deuteration shifts and compared with the structural analogues of these
      compounds. In IR spectra of the free-base porphyrins, the p-sulfonation of phenyl
      groups results in evident alteration for the phenyl modes and the porphyrin
      skeleton modes that are strongly coupled with phenyl vibrations. While the p
      sulfonation of phenyl groups causes only slight changes for the high-frequency
      Raman bands (> 850 cm(-1)), dramatic shifts and band splitting were observed in
      the low-frequency region (< 500 cm(-1)) of Raman spectra. The observed
      differences of low-frequency Raman spectra were attributed to the alteration of
      the structure of the porphyrin ring, especially the CalphaCmCalpha bond-angles,
      by different meso-sulfonatophenyl substitutions. In addition, different packing
      style of TPPSn molecules in the aggregates is also responsible for the alteration
      of the vibrational spectra of the aggregated TPPSn.

PMID- 12509151
TI  - Excited state complex formation between methyl glyoxal and some aromatic bio
      molecules: a fluorescence quenching study.
AB  - Fluorescence quenching of some important aromatic bio-molecules (ABM) such as 3
      aminophthalhydrazide (luminol), tryptophan (Try), phenylalanine and tyrosine
      (Tyr) by methyl glyoxal (MG) has been studied employing different spectroscopic
      techniques. The interaction of MG with ABM in the excited state has been analysed
      using Stern-Volmer (S-V) mechanism. In the case of MG-luminol system time
      correlated single photon counting (TCSPC) technique has also been applied to
      explain the S-V mechanism. The bimolecular rate constants obtained are found to
      be higher than the rate constant for diffusion controlled process. A plausible
      explanation of the quenching mechanism has been discussed on the basis of
      hydrogen bonding, charge transfer and energy transfer interaction between the
      colliding species.

PMID- 12509152
TI  - Effect of solvent on an NMR chemical shift difference between glycyl geminal
      alpha-protons as a probe of beta-turn formation of short peptides.
AB  - Proton NMR spectra of short peptides with a glycyl (Gly) or N-methylglycyl
      (sarcosyl, Sar) residue were measured in various mixed solvents with a wide range
      of dielectric constants: 78.3-2.3. From analyses of the octet and quartet signals
      of the geminal alpha-protons of Gly and Sar residues, respectively, we have
      estimated chemical shift differences between the two alpha-protons, Delta
      delta(alpha/alpha'). It is found that the Delta delta(alpha/alpha') values
      increase with decreasing solvent polarity and the increasing rates depend
      significantly on amino acid sequences. By referring to infrared spectra and
      chemical shift of the terminal NH protons, deltaNH, of the peptides, the Delta
      delta(alpha/alpha') values were found to be a good probe of beta-turn formation.
      From solvent-dependent change of Delta delta(alpha/alpha'), we estimated the free
      energies for the beta-turn formation and compared the results with those
      estimated from deltaNH. Using the resulting free energies, we have discussed
      effects of solvent on the beta-turn formation.

PMID- 12509153
TI  - Fourier transform infrared spectroscopy study of nanostructured nickel oxide.
AB  - Nanostructured nickel oxide having different average particle sizes ranging from
      3 to 16 nm were synthesized and Fourier transform infrared (FTIR) spectra of the
      samples were recorded in the far infrared (IR) region. The spectra were found to
      be dominated by surface mode absorptions with no distinct absorption
      corresponding to the bulk transverse optical mode. IR absorption coefficient,
      alpha, for the nanostructured NiO samples were calculated as a function of
      frequency using a macroscopic approach devised by Fuchs. The effects of
      crystalline geometry, numerical values of optical constants, filling factor and
      increased damping on the spectral features of the samples were analyzed. Though
      the simulations approximately reproduced the occurrence of a shoulder in the
      experimental spectra, the most intense peak in the simulated spectra was found to
      be about 50 cm(-1) above the corresponding experimentally observed peak. It was
      shown that the experimentally observed absorption maximum of all the samples were
      in close agreement with that determined using a microscopic theory based on the
      rigid ion model. The weak absorption peaks in the frequency region 60-100 cm(-1)
      appearing in the spectra of all the samples were identified as surface induced
      transverse acoustical modes, omegaTA, which became IR active due to the breakdown
      of translational symmetry in the nanocrystallites.

PMID- 12509154
TI  - High resolution electronic absorption spectra of anisole and phenoxyl radical.
AB  - High resolution absorption spectra of anisole and phenoxyl radical has been
      recorded in the vapor phase at room temperature by flash photolysis technique,
      and subsequent reactions have been investigated by kinetic spectroscopy. It was
      possible to follow the kinetics of the radical's decay which occurred
      predominantly by bimolecular recombination. The concentration of the phenoxyl
      radical calculated from the concentration of diphenoxyl molecules formed in the
      reaction cell during the optical pumping. The absolute extinction coefficient of
      this radical was measured from the absorption band at 291 nm, and found to be
      0.95 x 10(+4) mol(-1) 1 cm(-1).

PMID- 12509155
TI  - Barbituric and thiobarbituric acids: a conformational and spectroscopic study.
AB  - A conformational study on Barbituric (BA) and Thiobarbituric (TBA) acids was
      performed at ab initio MP2/6-31G** level on the neutral, protonated, mono- and di
      anionic forms. Acid-base equilibria were studied by comparing the electronic
      transitions evaluated for the most stable conformations and the experimental
      spectra at different pH values. The electronic transitions were obtained through
      the ZINDO approach.

PMID- 12509156
TI  - Rayleigh light scattering study on the supramolecular interactions of beta
      cyclodextrin derivatives with tetrakis(4-methoxylphenyl)porphyrin.
AB  - The supramolecular interactions of beta-cyclodextrin(beta-CD) and four kinds of
      alkylated beta-cyclodextrin (beta-CDs), i.e. heptakis (2,6-di-O-isobutyl)-beta
      cyclodextrin (Ob-beta-CD), heptakis (2,6-di-O-n-octyl)-beta-cyclodextrin (Oc-beta
      CD), heptakis (2,6-di-O-n-dodecyl)-beta-cyclodextrin (Od-beta-CD) and heptakis
      (2,6-di-O-n-hexadecyl)-beta-cyclodextrin (Oh-beta-CD) with tetrakis(4
      methoxylphenyl)porphyrin (TMOPP) have been investigated by Rayleigh light
      scattering (RLS) technique. Beta-CDs form 2:1 inclusion complex with TMOPP
      following an obvious RLS enhancement of TMOPP. The inclusion abilities of
      different beta-CDs were compared. The results show that the inclusion ability of
      beta-CDs is related to the size of the alkylated substituent. Thus, a new
      mechanism of inclusion interaction has been proposed. The exact stoichiometric
      ratios and the association constants of the inclusion complexes have been
      examined by application of curve fitting method.

PMID- 12509157
TI  - Electrochemical properties and Fourier transform-infrared spectroscopic
      investigations of the redox behaviour of poly(indole-5-carboxylic acid) in LiClO4
      acetonitrile solutions.
AB  - Electropolymerisation of indole-5-carboxylic-acid leads to the formation of
      electroactive polymer films. Potentiostatic deposition of the related polymer,
      poly(indole-5-carboxylic-acid), was carried out at a constant potential at 1.35 V
      versus SCE. The cyclic voltammogram of the resulting polymer in LiClO4 (0.15 mol
      dm(-3))/acetonitrile solution is characterized by two poorly resolved anodic and
      cathodic set peaks. FTIR spectroscopy was used to characterize both reduced and
      oxidized forms of poly(indole-5-carboxylic-acid). Assignments of the vibrational
      modes were proposed by comparison of the vibrational spectra of polyindole and
      polycyanoindole. The polymerization sites correspond to the 2 and 3 carbon
      positions of the pyrrole cycle. In the oxidized form of the polymer, the NH group
      is deprotonated while the quinoid form is present between the pyrrole rings.

PMID- 12509158
TI  - Vibrational study of new Pt(II) and Pd(II) complexes with functionalized nitrogen
      containing tertiary phosphine oxides. Ab initio study of ortho-, meta- and para
      dimethylphosphinylmethyleneoxyaniline.
AB  - Vibrational study of new Pt(II) and Pd(II) complexes of functionalized nitrogen
      containing tertiary phosphine oxides, namely ortho-, meta- and para
      dimethylphosphinylmethyleneoxyaniline (o-, m- and p-dpmoa),
      (CH3)2P(O)CH2OC6H4NH2, have been presented. Geometry optimization of the ligands
      was performed at HF/6-31G* and B3LYP/6-31G* levels of the theory. Harmonic
      frequencies were calculated at HF/6-31G* optimized geometries. Relative gas-phase
      and solution-phase (H2O and CH3CN) basicities of o-, m- and p-dpmoa ligands have
      been determined by ab initio calculations at STO-3G level with the Onsager
      reaction field model. On the basis of the vibrational study, physical and
      analytical data it was suggested that the ligands in the complexes studied
      coordinate through the amino group and form square-planar platinum and palladium
      complexes of the general formula ML2Cl2 (M = Pt, Pd, L = o-, m- and p-dpmoa).

PMID- 12509159
TI  - Vibrational spectroscopic studies on the natural product, columbianadin.
AB  - NIR-FT Raman and FT-IR spectra of columbianadin, extracted from seeds and roots
      of Heracleum candolleaum, were recorded and analyzed. The vibrational frequencies
      of the compound have been computed using semi-empirical AM1 method and compared
      with experimental values. The C=O stretching frequencies of the carbonyl groups
      have been lowered due to conjugation. The CH stretching and bending vibrations of
      CH3 groups of the ester part indicate the presence of hyperconjugation effect.
      Characteristic ring vibrations have also been identified.

PMID- 12509160
TI  - Ultraviolet spectrophotometric characterization of copper(II) complexes with
      imidazole N-methyl derivatives of L-histidine in aqueous solution.
AB  - In this study we considered pi-methyl-L-histidine (pi-methis) and tau-methyl-L
      histidine (tau-methis) as ligands for copper(II) ion, in order to clarify, by
      means of ultraviolet (UV) spectroscopy in aqueous solution (T = 25 degrees C, I =
      0.1 M), some aspects of the co-ordination mode with respect to other ligands of a
      previous study in which copper(II) complexes of L-histidine, N-acetyl-L
      histidine, histamine, L-histidine methyl ester or carnosine were investigated.
      Particularly, UV spectra (300-400 nm) were recorded on solutions at various pH
      values, containing each binary system Cu-L; afterwards, an UV absorption spectrum
      for single complexes was calculated, taking into account the chemical model
      previously assessed, in order to fulfil a correct spectrum-structure correlation.
      The problem related to the eventual superimposition of the CT shoulder
      (approximately 330 nm) to copper(II) of OH- and imidazole pyridine nitrogen
      groups were now solved by means of a comparison of the UV spectra of dimer
      species formed by both pi-methis or tau-methis. Finally, copper(II) complex
      formation with 2,2'-bipyridine was taken into account to compare the behaviour of
      pyridine (from 2,2'-bipyridine) and pyridine imidazole nitrogens (from pi-methis
      or tau-methis) with respect to the UV charge transfer process to copper(II) ion.

PMID- 12509161
TI  - Role of duration and interval in perception of force pulses.
AB  - Three experiments investigated the perceptual threshold for a pulsed force
      stimulation of the middle phalanx of the forefinger. The first experiment (N = 5)
      manipulated duration of the pulse, and the second (N = 6) manipulated the
      interval between pulses. Both experiments held magnitude constant. The results
      confirmed high reliability and indicated that perceptual threshold decreased as
      both Duration and Interval increased. Although subjects responded consistently,
      they described the sensation as "muscular" and "diffuse." Exp. 3 (N = 12)
      covaried Duration and Interval and found effects similar to those of the first
      two studies. Also, Duration and Interval were independent. Additional research is
      needed to clarify the relations of duration, interval, and magnitude in
      contributing to conscious perception of the presence of applied force. Treating
      pulse magnitude as a dynamic variable by varying its rate of change within a
      train of force pulses could further our understanding of how perception of force
      changes depend upon rate.

PMID- 12509162
TI  - Transcranial magnetic stimulation study of plastic changes of human motor cortex
      after repetitive simple muscle contractions.
AB  - Studies of use-dependent changes in neural activation have recently focused on
      the primary motor cortex. To detect the excitability changes in the primary motor
      cortex after practice in human subjects, motor-evoked potentials by transcranial
      magnetic stimulation during motor imagery after just 10 sessions of simple index
      finger abduction were examined. The present results indicate that width of the
      output map and amplitudes of motor-evoked potential became progressively larger
      until practice ended. These flexible short-term modulations of human primary
      motor cortex seem important and could lead to structural changes in the
      intracortical networks as the skill becomes more learned and automatic, i.e.,
      'adaptation' as one of the neural mechanisms related to motor learning.

PMID- 12509163
TI  - Sensation seeking and subjective unpleasantness ratings of stimulus intensity.
AB  - Zuckerman's Sensation Seeking Scale measures tendency to seek novel, varied,
      complex, and intense sensations and experiences and the willingness to take risks
      for the sake of such experiences. In this study, the subjective experience of
      sensory intensity change was explored by asking six high and six low sensation
      seekers to expose themselves to a combined sound and vibration stimulus that
      increased in intensity until one of three different levels of subjective
      unpleasantness was reached. Analysis showed that high sensation seekers
      consistently exposed themselves to longer periods of stimulation and thus higher
      intensities.

PMID- 12509164
TI  - Do landmarks help or hinder women in route learning?
AB  - Previous research on route learning has demonstrated that men learn routes faster
      and with fewer errors than women, whereas women are able to recall more landmarks
      along the route. The present study was aimed at investigating whether landmarks
      help or hinder women when they learn a route. 47 female and 37 male undergraduate
      students were randomly assigned to one of two conditions, in which they learned a
      route on a map with landmarks (the Landmark condition) or with no landmarks (the
      No-Landmark condition). Men outperformed women in the Landmark condition,
      learning the route in less time, with fewer errors, and in fewer trials than
      women did. In contrast, in the No-Landmark condition, no significant differences
      were found between men and women on the route-learning measures. Men learned the
      route faster and more accurately when landmarks were present than when they were
      not, but the performance of women was not affected by the presence or absence of
      landmarks. These results suggest that men and women may employ landmarks
      differently when learning a route. Men may use the positions of landmarks to make
      distance and direction judgments, whereas women may label the landmarks and
      memorize these labels, which interferes with learning the route.

PMID- 12509165
TI  - Relation of rated fatigue and changes in energy after exercise and over 14 weeks
      in previously sedentary women exercisers.
AB  - For 36 previously sedentary, asymptomatic women the relation of changes in
      Fatigue and Energy after exercise and over a 14-wk. period associated with
      participating in a moderate cardiovascular exercise program was analyzed. Scores
      on the Exercise-induced Feeling Inventory subscale of Physical Exhaustion
      significantly decreased, and those on the subscale of Revitalization
      significantly increased immediately after completion of exercise. Feeling state
      scores before exercise (high vs low on Physical Exhaustion and Revitalization)
      were not significantly associated with the change in scores on the subscales.
      Scores on the Profile of Mood States subscale of Fatigue significantly decreased
      and on the subscale of Vigor significantly increased over the 14-wk. study.
      Participants with initially higher Fatigue scores showed significantly greater
      mean change over the 14 wk. than those with lower scores. No such difference was
      found for changes in Vigor scores. Significant correlations between both measures
      of Fatigue (Physical Exhaustion and Fatigue) (r = .36) and Energy (Revitalization
      and Vigor) (r = .54) were found which indicated a relation between changes in
      feeling after exercise and those over 14 wk. Limitations and implications of the
      findings were discussed based on theories of exercise-induced affective change.

PMID- 12509166
TI  - Crossed hand-eye dominance in male psychiatric patients.
AB  - Increased incidence of left-eye and crossed hand-eye dominance have been
      considered as indicating left hemispheric dysfunction in many neuropsychiatric
      disorders. This study investigates the incidence of left-eye and crossed hand-eye
      dominance in patience with schizophrenia (n = 68), panic disorder (n = 62),
      personality disorder (n = 35), heroin addiction (n = 54), and mental retardation
      (n = 33), in comparison with controls (n = 944). All psychiatric groups, except
      the group with panic disorder, had significantly greater frequency of left-eye
      dominance than the control group. Furthermore, all psychiatric groups, except the
      personality-disordered group, had significantly greater frequency of crossed hand
      eye dominance than the control group. These findings further support the evidence
      of an anomaly in hemispheric lateralization among different psychiatric
      populations, particularly among those with psychotic symptoms and cognitive
      deficits.

PMID- 12509167
TI  - Effect of frequency on human unipedal hopping.
AB  - All mature forms of locomotion involve periods of unilateral stance. Unipedal
      hopping may provide useful information about the neuromuscular and biomechanical
      capabilities of a single lower extremity in adults. This study investigated
      whether hopping influenced vertical stiffness and lower extremity angular
      kinematics during human unipedal hopping. Vertical force and two-dimensional
      kinematics were measured in 10 healthy males hopping at three frequencies:
      preferred, +20%, and -20%. At +20%, compared to preferred, vertical stiffness
      increased 55% as hip flexion, knee flexion, and ankle dorsiflexion decreased,
      while at -20% vertical stiffness decreased 39.4% as hip flexion, knee flexion,
      and ankle dorsiflexion increased. As in bipedal hopping, the force-displacement
      relationship was more springlike at the preferred rate and +20% than at -20%.
      Given the prevalence of unilateral stance during walking, running, and skipping,
      findings related to unipedal hopping may be useful in the rehabilitation or
      conditioning of lower extremities.

PMID- 12509168
TI  - Variables affecting naming latency for Japanese Kanji: a re-analysis of Yamazaki,
      et al. (1997).
AB  - Yamazaki, Ellis, Morrison, and Lambon Ralph in 1997 demonstrated that written and
      spoken age-of-acquisitions had a stronger effect on the naming latency of single
      Kanji words than any other variable including familiarity. The present study was
      designed to reanalyze Yamazaki, et al.'s data, using the ratings of written and
      spoken age-of-acquisitions and visual and auditory familiarities taken from the
      NTT lexical database. This analysis showed that visual familiarity exerted a
      stronger independent effect on naming latency than two types of age-of
      acquisitions.

PMID- 12509169
TI  - Frequency of public laughter in relation to sex, age, ethnicity, and social
      context.
AB  - This study investigated the frequency of public laughter in a total of 10,419
      children, adolescents, young adults, middle-aged adults, and older adults.
      Females laughed significantly more than males, and younger people generally
      laughed more than older people.

PMID- 12509170
TI  - Practice effects on reaction time for peripheral and central visual fields.
AB  - The present study examined whether EMG-RT (RT) for a key press to stimulus in
      peripheral and central visual fields decreases with practice. 16 male students
      were divided into two groups, one practicing using peripheral vision, the other
      practicing using central vision. Before and after practice, RT was measured for
      peripheral and central visual fields. Each group practiced three blocks of 25
      trials five days a week for three weeks. RT for peripheral and central visual
      fields decreased with practice. Practice effects on RT for the peripheral visual
      field extended to RT for the central visual field, and vice versa. It is
      suggested that the transfer may reflect the decrease in the central nervous
      system's processing time in common between two RT tasks.

PMID- 12509171
TI  - Crying of a newborn child: alarm signal or protocommunication?
AB  - The purpose of the study was to explore whether the new-born cry is a simple
      alarm signal or differentiated cries with different meanings. 12 digital audio
      taped recordings of 6 full-term healthy babies were analysed. Cries of 6 newborns
      in this preliminary study were recorded in a pain condition after a prick for the
      hematic check-up the third day after delivery and then while crying spontaneously
      in the cradle. The sounds were sampled at 44100 Hz with a 16-bit resolution and
      converted to the .wav format. All the analyses were performed with a software
      written in the MAT-LAB environment. The most important result was that these new
      born children modulated the supralaryngeal tract considerably more in cries
      following the painful stimulus than in "spontaneous" ones, as would be expected
      by the hypothesis of crying as "protolanguage."

PMID- 12509172
TI  - Aesthetic judgments of novel graphic patterns: analyses of individual judgments.
AB  - Aesthetic judgments were investigated using a combined nomothetic and idiographic
      approach. Participants judged novel graphic patterns with respect to their own
      personal definitions of "beauty." Judgment analysis was employed to derive
      individual case models of judgment strategies as well as a group model. As
      predicted, symmetry had the highest correlations with aesthetic judgments of
      beauty. Stimulus complexity was the second-highest correlate of a positive
      evaluation. Thus, there was agreement at the group level. The judgment analyses,
      however, indicated substantial individual differences. These included use of
      symmetry or complexity cues that were contrary to the main group use, e.g., a few
      participants considered nonsymmetric patterns more beautiful. These findings
      suggest that exclusive consideration of the group model would have leveled the
      individual differences and been misleading. The group model is significant;
      however, the individual judgment analyses represent individual patterns of
      judgment in a notedly more accurate way.

PMID- 12509173
TI  - Detecting concentration differences in aromatic oils.
AB  - 200 University of Wolverhampton undergraduates rank-ordered samples of aromatic
      oils commonly used in complementary medicine in terms of their concentration in
      the air above an oil-soaked cotton ball. Each participant was assigned the task
      of discriminating between 5 microl, 10 microl, and 20 microl of oil absorbed onto
      cotton balls. 25 participants assessed each oil, and 8 oils were used. Cardamom,
      Rosemary, and Ylang Ylang were highly discriminable; however, discrimination of
      different concentrations of Chamomile, Cyprus, Geranium, Jasmine, and Lavender
      did not significantly differ from chance. These data provide useful indices for
      choosing aromatic oils for research purposes.

PMID- 12509174
TI  - Interest value, meaningfulness, and familiarity of words: relations with other
      word properties.
AB  - Evaluation of different properties of words and the relations among them is of
      value for understanding languages and as a basis for research. In the present
      study we investigated relations among interest value, familiarity, and
      meaningfulness of words. We also investigated the relations of these properties
      with imagery, concreteness, emotionality, frequency, date of entry into the
      language, word length, and amplitude of skin conductance response. A total of 85
      university students received a list of 25 word pairs, each pair comprised of a
      concrete and an abstract noun with related meanings, e.g., "friend" and
      "friendship," and rated the interest value, familiarity, and meaningfulness of
      each word. Familiarity correlated significantly with meaningfulness and interest
      value.

PMID- 12509175
TI  - Human pupil and eyelid response to intense laser light: implications for
      protection.
AB  - Natural ocular protective measures induced by laser glare at 514 nm were
      evaluated concomitant with the performance of a tracking task. Light-induced
      eyelid and pupil responses of 5 volunteers, 1 woman and 4 men, ages 23 to 60
      years, were recorded as they tracked a target moving at 0.3 degrees/sec. with an
      optical sight. Frame-by-frame analysis of video images of the eye allowed
      assessment of the eyelid response (squint and blink) and measurement of the pupil
      diameter. Three laser exposure durations (0.1, 1.0, and 3.0 sec.) were used
      during bright and dim ambient light conditions. All laser exposure trials
      produced a pupillary constriction with a latency, i.e., the time from the onset
      of the laser exposure until the pupil began to constrict, of approximately 100
      msec. In a representative 3-sec. exposure, the total intraocular energy was
      reduced by 69% as the pupil diameter decreased from 6.0 to 2.5 mm. For the 0.1
      sec. exposures at 1.6 mW/cm2, a blink reflex was observed on 2 of 10 trials under
      the dim ambient conditions and not observed on 9 trials under bright conditions.
      For 1- and 3-sec. exposures at 0.33 mW/cm2, a blink reflex was observed on four
      (3 bright and 1 dim) of the 38 trials. For conditions evaluated, pupillary
      constriction was consistent and provided some protection when the exposure
      duration exceeded the pupillary latency period; however, a blink reflex was
      observed on only a limited number of trials, possibly due to the exposure dose,
      the small retinal irradiance diameter produced by the laser exposure, and the
      volunteers' attention to the demanding performance task.

PMID- 12509176
TI  - Effects of order of report and stimulus type on multidimensional identification.
AB  - An experiment was conducted to investigate the effect of order of report and
      stimulus type on multidimensional stimulus-identification performance. Analysis
      showed that the proper order of reporting dimensional attributes depended on
      stimulus type. If the dimensions were independent heterogeneous attributes, the
      effect of order of report was not significant. If homogeneous attributes were
      involved, they should be reported consecutively. The order in which the color
      attributes should be reported depended on the characteristics of the stimulus
      dimensions. If there was a natural language-appropriate order of reporting the
      dimensional attributes, the color attribute should be used as an adjective and
      reported first. Otherwise, reporting color attribute later seemed to have an
      advantage because color is less vulnerable to memory deterioration.

PMID- 12509177
TI  - Students' learning through hypermedia.
AB  - This study assessed the effectiveness of hypermedia software in the learning and
      retention, association, and structuring of biological knowledge by using fifth
      grade students (ages 9 to 11 years) from three urban schools in Southern Chile.
      Four groups of 24 subjects each were exposed to either hypermedia software
      presentation on basic functions of the human body (Group 1), the same information
      in linear, electronic book mode (Group 2), the same information on a printed
      brochure (Group 3), or no experimental treatment but exposure (as were students
      in the other three groups) to regular lectures and materials (control group or
      Group 4). Six students from each school were randomly assigned to the treatment
      and control groups; thus 24 students from each school (N=72) participated.
      Students in all groups increased their retention of information. They also
      improved their performance on remote concept associations and on construction of
      conceptual maps. However, the groups who used the software presentation obtained
      significantly better scores on remote association of concepts. There were
      correlations for the users' hypermedia navigational patterns with the richness of
      the students' conceptual maps, and the students' remote association. In general,
      results support the use of similar software in education wherein the goals are
      remote associations and rich conceptual maps, and, more specifically, they
      indicate that the students' navigational pattern through information could serve
      them better to structure and relate conceptual information.

PMID- 12509178
TI  - Attention can be oriented to intermediate locations within the large area of the
      visual field.
AB  - The present study examined whether attention can be evenly distributed within the
      large area of the visual field. The stimulus was presented at one of four
      locations on the horizontal meridian (0 degrees, 10 degrees, 20 degrees, and 30
      degrees to the right). In the Fixed Location condition, the stimulus appeared
      repeatedly at the same location. In the Random Location condition, the stimulus
      appeared at one of four locations as determined randomly with equal probability.
      Reaction times (RTs) in the Random Location condition were significantly longer
      than those in the Fixed Location condition at the 0 degrees and 30 degrees
      locations, while there were no significant differences at the 10 degrees and 20
      degrees locations. The differences in the RT between conditions were
      significantly larger at the 0 degrees and 30 degrees locations than those at the
      10 degrees and 20 degrees locations. These results suggest that attention was
      oriented to intermediate locations within the large area of the visual field.

PMID- 12509179
TI  - Hand preference, susceptibility to motion sickness, and differential
      vulnerability to psychiatric admission.
AB  - Nonright-handers (n = 192) were more common within an inpatient psychiatric
      population of 792 than in a control nonpatient population of 559. Vulnerability
      of nonright-handers to admission appears to be associated with an intermediate
      extent of susceptibility to motion sickness.

PMID- 12509180
TI  - Sleep EEG patterns and fatigue of middle-aged and older female family caregivers
      providing routine nighttime care for elderly persons at home.
AB  - The sleep EEGs and fatigue of 9 female family caregivers (age M=65 yr.) and 9
      female noncaregivers (age M=67 yr.) were measured during two successive nights at
      their houses. Perceived quality of sleep was measured by the Sleep Evaluation
      Questionnaire. Fatigue was measured by a self-rated questionnaire, the Perceived
      Symptoms of Fatigue, and by critical flicker fusion (CFF) frequency. The
      caregivers had a significantly higher percentage of Stage 1 and a lower
      percentage of Stage 2 during the 2nd cycle and a higher percentage of Stages 3+4
      during the 3rd cycle than those of the noncaregivers. Caregivers had
      significantly higher percentages of EEG waves of 7-9 Hz in the 1st cycle and 6-9
      Hz in the 2nd cycle and significantly lower percentages of 2-3 Hz in the 1st
      cycle than those of the noncaregivers. The caregivers reported a lower quality of
      sleep and higher perceived fatigue symptoms and also lower CFF frequency
      (increased physiological fatigue) than noncaregivers. The caregivers' sleep EEGs
      were associated with their higher sleep needs and fatigue.

PMID- 12509181
TI  - Colour blindness in Italian art high school students.
AB  - To highlight the link between colour blindness and school achievement, the
      Ishihara and Farnsworth tests were administered to 3,565 high school art students
      (2,545 girls and 1,020 boys). Analysis showed colour defective students were
      discriminated against in theoretical subject matter, relative to orthochromate
      students, but not in the art-related subjects. This emphasizes the need to
      recognize youth with colour defective vision early.

PMID- 12509182
TI  - Hand preference and length of psychiatric hospital stay by month of admission.
AB  - Length of psychiatric hospital stay is higher for patients admitted in the months
      of April and May. This effect was strongly associated with handedness and was
      greatest for left-handers. The duration of hospitalization of left-handed
      subjects admitted in April and May was, on average, 88.5% longer than for left
      handed subjects admitted during any other period. In contrast, length of stay for
      right-handed patients differed by no more than 16% between any months compared.

PMID- 12509183
TI  - A Monte-Carlo estimation of effect size distortion due to significance testing.
AB  - A Monte-Carlo study was done with true effect sizes in deviation units ranging
      from 0 to 2 and a variety of sample sizes. The purpose was to assess the amount
      of bias created by considering only effect sizes that passed a statistical cut
      off criterion of alpha = .05. The deviation values obtained at the .05 level
      jointly determined by the set effect sizes and sample sizes are presented. This
      table is useful when summarizing sets of studies to judge whether published
      results reflect an accurate appraisal of an underlying effect or a distorted
      estimate expected because significant studies are published and nonsignificant
      results are not. The table shows that the magnitudes of error are substantial
      with small sample sizes and inherently small effect sizes. Thus, reviews based on
      published literature could be misleading and especially so if true effect sizes
      were close to zero. A researcher should be particularly cautious of small sample
      sizes showing large effect sizes when larger samples indicate diminishing smaller
      effects.

PMID- 12509184
TI  - College-age males' ability to produce the acoustic properties of an aging voice:
      some suggestions for further exploration.
AB  - Manning, et al. recently reported on the ability of college-age males to imitate
      the voice of an aging male. This commentary briefly discusses how their data
      could be extended to support their published findings.

PMID- 12509185
TI  - Test-retest reliability and factor stability of the behavioral evaluation for
      epidemiology studies test battery.
AB  - The Behavioral Evaluation for Epidemiology Studies test battery uses touch-screen
      technology and novel methodologies to enhance neurobehavioral assessment. Scores
      generally show differential stability from the first trial with individual test
      reliabilities at or above .80 when normalized to a 3-min. administration. Six
      highly reliable (r > or = .87) factors were identified that cover functions known
      to be sensitive to neurotoxicants and physical exposures. These results strongly
      support recommendation of the new test battery for use in repeated-measures
      epidemiologic studies where first trial stability is desired.

PMID- 12509186
TI  - Influence of contextual stimuli on line bisection.
AB  - The influence of contextual stimuli on line-bisection performance was
      investigated. Subjects were required to bisect lines flanked at one end by one
      pair of solid black rectangles. Bisection was performed along three orthogonal
      axes (horizontal, radial, vertical). The results showed the presence of a
      bisection bias in the direction opposite to the location of flanking rectangles.
      This finding suggests that the presence of rectangles beside one end of a line
      interfered with representation of the line as a whole and induced the subjects to
      neglect the flanked part of the line.

PMID- 12509187
TI  - Hand preference and diagnosis in major mental illness.
AB  - A sample of 1,671 patients in a long-term psychiatric inpatient hospital were
      polled for hand preference in writing. Nonright-handers (n = 420) were more often
      diagnosed schizophrenic than Right-handers (n = 1,251), but the overall
      proportion of psychotic illness was the same in both handedness groups,
      suggesting the possibility that nonright-handedness may be associated with a
      change in the expression of psychotic illness so it is somewhat more likely to be
      manifest as thought disorder than mood disorder.

PMID- 12509188
TI  - Rorschach measures during depth hypnosis and suggestion of a previous life.
AB  - Using a procedure with suggestions to prompt false memories from an alleged
      previous life, we hypnotized 16 normal subjects and collected Rorschach data
      before and during the hypnotic induction. During hypnosis 9 subjects produced
      memories that they claimed to remember from a former life. The Rorschach findings
      bore no resemblance to the available data for other dissociative disorders.
      Rorschach variables during hypnotic trance remained almost unchanged from
      baseline. These results indicate that the Rorschach poorly reflects hypnotic
      trance.

PMID- 12509189
TI  - Regional variation of divorce in Germany.
AB  - The correlates of provincial divorce rates in Germany in 1996 were marriage
      rates, birth rates, population density, and formerly East versus West Germany.

PMID- 12509190
TI  - Hand preference and spring-summer vs fall-winter seasonal affective disorder.
AB  - Left- and right-handed patients with seasonal affective disorder were compared
      for seasonal patterns of depression and good spirits. Spring-summer depression
      and fall-winter good spirits were more evident among 9 left-handers. The reverse
      pattern was observed for the 9 right-handers.

PMID- 12509191
TI  - More on magnitude of priming in implicit memory tasks.
AB  - The effects of word frequency, length of the word, and type of word fragment in a
      fragment-completion test were investigated with 57 undergraduate students, 19-22
      years. Priming with better performance on studied than on nonstudied words in
      this task was greater for low frequency words than for high frequency words and
      greater for fragments without the first letter than for fragments with the first
      letter. It was inferred that characteristics of fragments should be considered in
      any implicit memory task when the magnitude of priming is of interest. In
      general, word fragment-completion processes appear to be based on sources of
      information available in visual identification tasks.

PMID- 12509192
TI  - Knowledge of results and explicit instruction: efficiency of learning the crawl
      stroke in swimming.
AB  - Specific verbal instructions when added to simple knowledge of results during
      learning the crawl stroke by 4 adult novices was followed after 1 mo. of no
      practice by a higher index of swimming than observed for 4 novices given only the
      qualitative knowledge of results.

PMID- 12509193
TI  - The brain matrix and multifocal brain damage following a single injection of
      ketamine in young adult rats: conspicuous changes in old age.
AB  - Male rats were seized with lithium and pilocarpine and then injected within 30
      min. with either acepromazine or ketamine. These rats as well as age-matched
      normal rats were observed daily for one year. The rats which had received the
      ketamine after the seizures were significantly heavier than either the normal
      rats or the other group of seized rats. The bulk of this increased weight was due
      to the marked increase in white, extremely dense adipose tissue. Compared to the
      acepromazine-treated rats, the ketamine-treated rats did not exhibit spontaneous
      seizures and exhibited cerebral widths comparable to normal rats. These results
      suggest that the multifocal, graded neuronal loss associated with this seizure
      model may allow other "configurations" to emerge that can support normal
      behaviors as well as new characteristics.

PMID- 12509194
TI  - Visual search strategies in experienced and inexperienced gymnastic coaches.
AB  - The visual search strategies employed by gymnastic coaches with different levels
      of expertise were investigated. Expert (n=3) and novice coaches (n=3) watched 9
      video sequences of 3 gymnastic techniques and were required to highlight errors
      in performance. Visual search patterns were monitored by an ASL-5000SE eye
      tracking system during observation. Expert participants showed longer and fewer
      visual fixations than the novice group.

PMID- 12509195
TI  - Kandinsky's questionnaire revisited: fundamental correspondence of basic colors
      and forms?
AB  - Kandinsky postulated a fundamental correspondence between color and form. Using a
      variant of his historical questionnaire, 200 (92 men, 108 women) nonartist
      university students were divided into two groups and asked to assign the colors
      yellow, red, and blue to the triangle, square, and circle in a one-to-one
      fashion. One group worked under a mere color-form correspondence instruction, the
      other under an aesthetic-correspondence one, i.e., this latter group was asked to
      make the most beautiful color-form assignment. Participants' assignments showed a
      clear, stable group preference. About half of the students assigned red to the
      triangle, blue to the square, and yellow to the circle, respectively. This
      preferred assignment stood regardless of variation in instruction. Frequently,
      world knowledge associations were stated in the rationale for an assignment
      choice. The red triangle resembled a traffic sign, a warning triangle, and the
      yellow circle resembled the sun. Kandinsky's assignment, however, was the least
      preferred one. It is argued that color-form assignments as well as the motivation
      to produce them are due to a multitude of factors. World knowledge, education,
      historical change, societal, group-specific, and individual leitmotifs are all
      influences.

PMID- 12509196
TI  - Achievement in chemistry problem-solving as a function of the mobility-fixity
      dimension.
AB  - The present studies explored the relation between students' achievement in
      chemistry problem-solving and the Mobility-Fixity dimension. Fixity characterizes
      consistency of function of field-independent subjects in a field-independent
      fashion, while Mobility provides for variation according to circumstances. The
      effect of this cognitive variable was examined as a function of the type and the
      complexity of the problem. Two kinds of problems were used, chemical equilibrium
      problems with varying mental demand and logical structure, and organic synthesis
      problems with varying mental demand. The subjects had to carry out different
      mental tasks, such as manipulation of logical schemata, applying algorithmic
      procedures, solving nonalgorithmic problems. In all cases, Mobile subjects
      demonstrated higher achievement than Fixed subjects. The results of this study
      support the hypothesis that the Mobility-Fixity dimension can serve as a
      predictor variable of students' performance on chemistry problem-solving.

PMID- 12509197
TI  - Relation of reading rate and rapid automatic naming among third graders.
AB  - The relation of reading rate and rapid automatic naming (RAN) for pictures was
      investigated for 31 third graders. Reading rate was measured as the number of
      seconds required for reading aloud a third-grade passage. Rapid automatic naming
      was assessed with the RAN portion of the Woodcock Johnson III Tests of Cognitive
      Abilities. A moderate correlation of -.61 between the sets of scores suggests RAN
      assessment may be useful in screening for reading deficits in third-grade
      children.

PMID- 12509198
TI  - Unidimensionality of the Chinese version of the Foreign Language Reading Anxiety
      Scale.
AB  - Previous research showed the Foreign Language Reading Anxiety Scale is reliable
      and valid for assessing reading anxiety in groups of American college students
      beginning study of French, Japanese, or Russian. Because Saito, Horwitz, and
      Garza (1999) reported that reading anxiety tends to vary with the target
      language, the present investigation examined the factorial validity of the
      Chinese version of the scale in college students of English as a foreign language
      in Taiwan, Confirmatory factor analysis with maximum likelihood method supports
      the unidimensionality of the scale, which is reliable and valid for eliciting
      reading anxiety of Chinese college foreign language learners and for predicting
      their global language performance. This study suggests exploring how language
      proficiency, culture, and topic familiarity may be related to such anxiety.

PMID- 12509199
TI  - Metamorphological awareness and EFL students' memory, retention, and retrieval of
      English adjectival lexicons.
AB  - Research has shown that foreign or second language learners' metalinguistic
      awareness has important effects on their acquisition of the target language.
      Important among a multitude of the concerns are problems these learners encounter
      when they have to process the morphological features of individual words,
      particularly in the acquisition of literacy skills. Nevertheless, for students
      who learn English as a foreign or second language for academic purposes, one of
      the biggest challenges in their advanced study is how they can effectively
      remember, retain, and retrieve the colossal number of newly learnt English
      vocabulary, including adjectival lexicons, to enhance their academic success.
      Results from the present report on the effects of metamorphological awareness of
      65 adult Chinese EFL learners' memory, retention, and retrieval of adjectival
      lexicons show that, although the subjects in the two groups did not differ
      significantly in their performance on a pretest designed to check their lexical
      knowledge and no sex difference was observed, statistically significant
      differences were found between the two groups in both conditions (immediate and
      delayed retrievals) on a posttest. The experimental group and women predominantly
      performed better in the memory-retention-retrieval tasks assigned to them.
      Implications for educational research and practices are also discussed.

PMID- 12509200
TI  - Social desirability bias and direction modified Competitive State Anxiety
      Inventory-2.
AB  - This study examined the relation between social desirability bias and responses
      to the direction modified Competitive State Anxiety Inventory-2 for male soccer
      players (37 professionals, 40 semiprofessionals, and 40 varsity players; M age =
      24.5 yr., SD=3.7) who completed the inventory and Reynolds' 13-item short form of
      the Marlowe-Crowne Social Desirability Scale one hour prior to a competitive
      match. Intraclass correlations were calculated to assess the relation between the
      two sets of scores. Out of the 18 correlations calculated, i.e., 6 subscales x 3
      skill levels, 17 were significant (p<.05), ranging from .38 to .70. The highest
      correlations were found among professional players and the lowest amongst the
      varsity players, but most of the differences were not statistically significant.
      These results indicate that scores on both the Intensity and Direction subscales
      of this anxiety inventory are significantly related to the tendency to self
      report socially desirable answers. Therefore, care should be taken when
      interpreting data from studies using the inventory, and social desirability
      measures should be taken whenever using this questionnaire.

PMID- 12509201
TI  - Effects of daily or weekly thermal (footpad) stress upon manifestation of
      melanoma tumours.
AB  - A total of 48 C57 male and female mice received thermal stimulation to their
      footpads either daily, weekly, or never. After either two or three weeks of this
      treatment the mice were injected to discern if the initiation of carcinogenic
      cell proliferation during a stressful period would influence the rate of
      development of the tumour. The latency in days for the onset of a discernable
      node over the injection site was measured. A statistically significant
      interaction between the temporal pattern of treatments and sex explained about
      25% of the variance in the latency of the appearance of tumours. Post hoc
      analysis showed the source of interaction involved the group that had not
      received the thermal stress. The results may suggest that either weekly or daily
      thermal stress may have reduced the females' resistance to tumorigenesis.
      However, this pattern and type of stress did not influence the first appearance
      of these skin tumours in the males.

PMID- 12509202
TI  - Dynamics of brain electric field during recall of Salpuri dance performance.
AB  - The brain wave activity of a professional Salpuri dancer was observed while the
      subject recalled her performance of the Salpuri dance when sitting in a chair
      with closed eyes. As she recalled the feeling of the ecstatic trance state
      induced by the dance, an increase in alpha brain activity was observed together
      with marked frontal midline theta activity. Compared to a resting state, the
      dynamics of the electrical activity in the brain showed an increase in the global
      field power integral and a decrease in generalized frequency and spatial
      complexity.

PMID- 12509203
TI  - Gestalt concept of closure: a construct without closure.
AB  - This comment reviews the original Gestalt literature which introduced the concept
      of 'closure'. It is argued that the meaning of 'closure' was confounded in the
      source literature and, thus, the term connotes more than it denotes. Research
      based on different measures of this ambiguous construct inevitably may not always
      converge.

PMID- 12509204
TI  - Physical exercise and time of day: influences on spontaneous motor tempo.
AB  - To identify whether spontaneous motor rhythm is influenced by external or
      internal events and whether this rhythm fluctuates across the day in parallel
      with heart rate diurnal variations, we simultaneously recorded heart rate and
      spontaneous motor rate before and after a pedaling task performed five times a
      day by 10 healthy human subjects. Each subject performed a Spontaneous Motor
      Tempo, i.e., a finger-tapping task, at a comfortable and spontaneous cadence. Pre
      and postexercise Spontaneous Motor Tempo was measured as well as heart rate.
      There were diurnal variations in Spontaneous Motor Tempo. Both measures increased
      significantly after pedaling, suggesting that cardiac and spontaneous rhythms are
      influenced simultaneously after a moderate exercise. Also, finger-taps occurred
      most frequently around the initiation of the heart systole. These results suggest
      that a putative internal clock might regulate Spontaneous Motor Tempo and that
      cardiac rhythm might influence this tempo.

PMID- 12509205
TI  - Influence of stimulus distance in implicit learning of spatial and nonspatial
      event sequences.
AB  - The serial reaction time task has been widely used to investigate implicit
      learning mechanisms. In the present study, we investigated the effect of stimulus
      distance on learning of a spatial sequence independent of a sequence of
      responses. Participants had to respond to objects appearing at four different
      locations. The objects were presented in a sequence of nine elements, whereas the
      location at which an object was presented followed a sequence of eight elements.
      Thus, the spatial and the object sequences were independent of each other. Four
      groups of subjects for whom the distances of the locations chosen to present
      objects on the computer screen (3 cm, 6 cm, 12 cm, or 22 cm) differed were
      tested. Only the nonspatial sequence was learned as indicated by enhanced
      response latencies in nonsequenced random blocks. Stimulus distance had no effect
      on the amount of sequence learning. Additional analyses for subgroups of subjects
      who did not show explicit knowledge of the sequences after completion of the task
      indicated that for implicit learners also, sequence learning was not influenced
      by stimulus distance. The results are discussed with respect to current theories
      of implicit serial learning.

PMID- 12509206
TI  - Blood type and bipolar disorder.
AB  - Type I bipolar patients in Budapest were reported to have type O blood more often
      and types A and B blood less often than Type II bipolar patients.

PMID- 12509207
TI  - Possible disruption of remote viewing by complex weak magnetic fields around the
      stimulus site and the possibility of accessing real phase space: a pilot study.
AB  - In 2002 Persinger, Roll, Tiller, Koren, and Cook considered whether there are
      physical processes by which recondite information exists within the space and
      time of objects or events. The stimuli that compose this information might be
      directly detected within the whole brain without being processed by the typical
      sensory modalities. We tested the artist Ingo Swann who can reliably draw and
      describe randomly selected photographs sealed in envelopes in another room. In
      the present experiment the photographs were immersed continuously in repeated
      presentations (5 times per sec.) of one of two types of computer-generated
      complex magnetic field patterns whose intensities were less than 20 nT over most
      of the area. WINDOWS-generated but not DOS-generated patterns were associated
      with a marked decrease in Mr. Swann's accuracy. Whereas the DOS software
      generated exactly the same pattern, WINDOWS software phase-modulated the actual
      wave form resulting in an infinite bandwidth and complexity. We suggest that
      information obtained by processes attributed to "paranormal" phenomena have
      physical correlates that can be masked by weak, infinitely variable magnetic
      fields.

PMID- 12509208
TI  - Applying contextual interference to snowboarding skills.
AB  - This investigation was designed to apply contextual interference to acquisition
      of snowboarding skills. 20 participants completed several acquisition stages
      lasting about 2 hours while either alternating the direction of the turn within
      each stage or completing the whole stage while attempting turns in one direction,
      then repeating the stage for the other direction of turn. Following acquisition,
      all participants returned 1 wk. later for a retention test. Alternating practice
      yielded better performance during acquisition and retention as measured by the
      arc and form attained within the turns. Because this differs from typical
      contextual interference effects, it is suggested that the relation between the
      skills may have affected the results. Negative transfer operating within blocked
      practice and increased between-task comparisons within alternating practice may
      be related to the similarity between the tasks.

PMID- 12509209
TI  - "Dark shading" of words in the diary of a suicide.
AB  - The use of dark-shading words declined over time in the diary of a suicide, a
      result opposite to that predicted.

PMID- 12509210
TI  - Test-retest stability of body-image scores in a sample of 12- to 14-yr.-olds.
AB  - The present study investigated test-retest variation in Body Image Questionnaire
      scores among a sample of British school children. 112 participants from three
      different school years (aged 12 to 14 years) completed the Body Image
      Questionnaire on two occasions separated by a 6-wk. period. No intervention
      designed to change perceptions of body shape took place, hence, tesr-retest
      scores should be stable. Analysis indicated a significantly greater variation
      among 12- and 13-yr-olds upon retest, but not for 14-yr.-olds. Research is needed
      investigating factorial and test-retest stability of the measure for use with
      children aged 12 or under.

PMID- 12509211
TI  - The Mozart effect may only be demonstrable in nonmusicians.
AB  - The "Mozart effect" is the tendency to score higher on spatiotemporal IQ
      subscales following exposure to complex music such as Mozart's Sonata K.448. This
      phenomenon was investigated in 20 musicians and 20 nonmusicians. The trion model
      predicts increased synchrony between musical and spatiotemporal centres in the
      right cerebral hemisphere. Since increased left-hemispheric involvement in music
      processing occurs as a result of music training, predictions deriving from the
      possibility of increased synchrony with left-hemispheric areas in musicians were
      tested. These included improved performance on language as well as spatiotemporal
      tasks. Spatiotemporal, synonym generation, and rhyming word generation tasks were
      employed as was the Mozart Sonata K.448. A Mozart effect was demonstrated on the
      spatiotemporal task, and the facilitatory effect of exposure to Mozart was
      greater for the nonmusician group. This finding adds to the robustness of the
      Mozart effect since novel tasks were used. No Mozart effect was found for either
      group on the verbal tasks, although the musicians scored higher on rhyming word
      generation. This new finding adds to the number of nonmusical tasks apparently
      showing long-term benefits from music training. However, no systematic link was
      found between performance on any task and number of years spent in music
      training. The failure to induce a Mozart effect in the musician group on verbal
      tasks, as well as that group's limited facilitation on spatiotemporal tasks, may
      be associated with either a ceiling effect due to the long-term effects of music
      training or from methodological factors. Both possibilities are discussed.

PMID- 12509212
TI  - The South African Bone Marrow Registry (SABMR): a 10-year review.

PMID- 12509213
TI  - Circulating highly fluorescent reticulocytes to predict the adequate harvesting
      of peripheral blood progenitor cells in platinum-based chemotherapy.
AB  - We prospectively evaluated whether peripheral blood progenitor cells (PBPC) yield
      from a single leukapheresis could be predicted by measurement of circulating
      highly fluorescent reticulocytes (HFR). PBPC were collected from 46 leukaphereses
      in 15 patients with gynecological cancer following platinum-based chemotherapy.
      Once a level of at least 5.0% HFR was achieved, sufficient PBPC were collected in
      a single harvest in 71% of the procedures. Whereas, failure to mobilize
      sufficient PBPC occurred in 24 of 28 leukaphereses when the percentage of
      circulating HFR was less than 5.0%. In conclusion, circulating HFR may aid in the
      efficiency of PBPC collections in platinum-based chemotherapy.

PMID- 12509214
TI  - Increased serum erythropoietin concentration after allogeneic compared with
      autologous blood transfusion.
AB  - Serum erythropoietin (sEPO) level is known to increase as hemoglobin (Hb)
      concentration decreases during and after preoperative autologous blood donation
      (PAD). The endogenous erythropoietin (EPO) production after allogeneic blood
      transfusion has not to our knowledge, been studied. The aim of the present study
      was to determine whether there is, after surgery, any change in sEPO
      concentration after allogeneic blood transfusion, and whether there is any
      difference in EPO response after autologous or allogeneic blood transfusion.
      Thirty-one patients approaching total hip-joint replacement surgery, were
      randomized to receive either allogeneic red blood cells (n = 15) or predeposited
      autologous whole blood transfusion (n = 16). The relationship between Hb, sEPO,
      and reticulocytes in the recipients were repeatedly analyzed before, during and
      after surgery. The Hb followed an expected pattern, with a decreased
      concentration after PAD in the autologous group, then in both groups after
      surgery. The sEPO concentration was significantly higher in the allogeneic than
      in the autologous group on day one and day 4-5 postoperatively. The reticulocyte
      level, on the contrary, was higher in the autologous patients before, one hour
      after, and one day after surgery. The study showed a greater increase in sEPO
      concentration after allogeneic blood transfusion than after autologous blood
      transfusion. There may be an inverse relationship between sEPO and the
      reticulocyte level.

PMID- 12509215
TI  - Serum transferrin receptor is a marker of iron deficiency in patients included in
      programs for preoperative autologous blood donation.
AB  - Recently programs for preoperative autologous blood donation (PABD) have expanded
      to reduce the need for allogenic blood transfusion. Nevertheless, the ability of
      the patients's bone marrow to replace the red blood cells (RBCs) mass reduced by
      phlebotomies determines the efficacy of PABD. In mild anemia, known as iron
      deficient erythropoiesis (IDE) or iron deficiency without anemia, precipitated by
      PABD, the marrow response is suboptimal and needs adjuvant therapy. The aim of
      this study was to evaluate the use of the serum transferrin receptor (sTfR) for
      the assessment of IDE in patients undergoing PABD. METHODS: Two autologous blood
      units from 50 consecutive patients scheduled for elective orthopedic surgery were
      collected preoperatively. Serial measurements of RBCs, haematocrit (Hct),
      haemoglobin (Hb), serum iron, serum ferritin, reticulocyte count, reticulocyte
      maturity index (RMI), endogenous erythropoietin (EPO) and sTfR were performed
      throughout the phlebotomy program. RESULTS: RBC, Hct, Hb and serum iron
      significantly decreased although within the normal range. There was no change in
      serum ferritin levels. Reticulocytes, RMI and EPO significantly increased as did
      sTfR which significantly exceeds the normal range. CONCLUSIONS: These results
      demonstrate that the sTfR is a reliable laboratory marker for detecting mild
      anemia or IDE. In patients undergoing PABD increased sTfR levels may suggest a
      treatment with recombinant human EPO (rh-EPO) or iron to improve the bone marrow
      performance.

PMID- 12509216
TI  - Prediction of fetal Rh D and Rh CcEe phenotype from maternal plasma with real
      time polymerase chain reaction.
AB  - Real-time PCR methods for the detection of RHD and the C, c, and E allele of RHCE
      were applied for the prediction of fetal Rh phenotype using maternal plasma. In
      one of 36 samples investigated the DNA extraction failed. When we tested the
      remaining 35 samples for Rh antigens which were absent on the mother's red cells,
      the fetal D-status was correctly determined in 26 of 27 cases (1 false negative).
      Fetal C was tested correctly in 23 samples, c was true positive in the only c
      negative woman and the fetal E-status was correctly determined in 35 cases. In
      conclusion real-time PCR of maternal plasma is a non-invasive method to determine
      fetal RH genotype. However, more studies are required for routine applications
      because the method is not 100% sensitive.

PMID- 12509217
TI  - IFN-gamma and TNF-alpha production in gamma-irradiated blood units by mononuclear
      cells and GVHD prevention.
AB  - Gamma-radiation of blood products is considered the mainstay of transfusion
      associated graft-versus-host disease prevention. Previous studies have detected
      lymphocyte inhibition rate in blood components just one time after irradiation
      but there is evidence of cellular variability with production of cytokines at
      different storage time which could be related with irradiation activity and
      cellular damage repair. IFN-gamma, a Th1 cytokine, and TNF-alpha, a pro
      inflammatory one, had a central role in the stimulation of cellular and
      inflammatory reactions. In this study whole blood was collected from five
      volunteer healthy donors and each donor bag was divided into two satellite bags:
      one of them was exposed to 137Cs-irradiation with a 2500 cGy dose. Samples for
      cytokine production, detected by ELISA methods, and proliferative response,
      evaluated by incorporation of H3 thymidine, were taken at the following storage
      time: 0, 24, 48, 72 and 96 h. The time-response curve of irradiated mononuclear
      cells from blood bags (BBMC) in mitogenic activation showed a time-related
      inhibition of cell proliferation with an enhanced response only after 24 h of
      storage and about 84% inhibition at 96 h. A similar pattern is follow by IFN
      gamma production after OKT3 stimulation. TNF-alpha levels both in
      lipopolysaccharide stimulated or unstimulated cells were always high. This data
      suggest that BBMC cells maintain the ability to produce cytokines after gamma
      radiation. On the ground of this study seems to be necessary to evaluate
      hypothetical risk associated with the administration of cytokine via irradiated
      blood components.

PMID- 12509218
TI  - Expression of CD47 (integrin-associated protein) decreases on red blood cells
      during storage.
AB  - In light of recent studies that demonstrate that CD47 antigen is an important
      "self-recognition" marker involved in protecting circulating red blood cells
      (RBCs) from phagocytosis by macrophages, the aim of the present study was to
      investigate whether CD47 expression on RBCs is altered during storage. Red cell
      concentrates (RCCs) were prepared and stored at 4 degrees C and samples were
      collected on days 1, 14, 28 and 42 post donation. RBCs were labelled with anti
      CD47 antibody and analysed by flow cytometry. A small but significant and
      progressive decrease in CD47 antigen expression was observed in non-irradiated
      and irradiated RBCs stored for 14 days onwards. CD47 was also detected in
      increasing quantities in supernatant from RCCs after 14 days of storage. It is
      proposed that loss of CD47 during storage, in addition to other biophysical
      changes, may target many transfused RBCs for clearance from the transfusion
      recipient's circulation.

PMID- 12509219
TI  - Phosphatidylserine exposure in platelet concentrates during the storage period:
      differences between the platelets collected with different cell separators.
AB  - BACKGROUND AND OBJECTIVES: Platelet alterations occur during the production and
      storage of platelet concentrates, the so called "storage lesion". We studied the
      platelet alterations during the storage period in apheresis concentrates,
      employing flow cytometry for phosphatidylserine (PS) detection on platelets
      during the five days of storage. MATERIAL AND METHODS: Twenty-seven single donor
      platelet concentrates harvested with the Cobe Trima, Baxter Amicus, or
      Haemonetics MCS+ were analyzed for PS exposure by flow cytometry on the day of
      production (day 1) and on days 3 and 5 of storage. Furthermore PS expression was
      analyzed in platelet donors' blood samples withdrawn before plateletpheresis.
      RESULTS: PS expression on platelets gave the following median values: in blood
      donors before apheresis it was 1.12% (0.13-1.78) in platelets concentrates on the
      first day (2 h after apheresis) 2.06% (0.66-15.2), the third day 6.57% (1.98
      51.13) and the fifth day 23.04% (3.86-80.23). All differences between median
      values of PS expression in blood samples before apheresis, and platelets
      concentrates on days 1, 3 and 5 of storage, are statistically significant. The
      expression of PS in platelet concentrates was analyzed in relation to the blood
      cell separator used for the collection procedure and showed the following
      results: on day 1 the median values of PS in platelet concentrates collected with
      the three different blood cell separators, Trima, Cobe and MCS, did not show
      statistically significant differences. On day 3, the platelets concentrates
      collected with the Trima and with the MCS showed differences that were
      statistically significant. Those were respectively 10.59% (4.56-51.13) and 3.53%
      (1.98-12.61), p = 0.005. The PS expression in platelet concentrates collected
      with the Trima and MCS showed differences that are also statistically significant
      on day 5 at respectively 32.4% (9.61-80.23) and 8.57% (3.86-48.42), p = 0.005.
      CONCLUSIONS: PS exposure in platelet concentrates on days 3 and 5 rise to levels
      that could compromise the quality of the platelet units. Improvements in
      standardized platelet quality controls, and in platelet collection systems are
      required to reduce the storage lesions in platelets concentrates.

PMID- 12509220
TI  - Quality control of platelets during storage by the PFA-100: a comparison to
      platelet aggregation.
AB  - BACKGROUND AND OBJECTIVES: The PFA-100 examines platelet function by measuring
      closure time (CT) when whole blood is passing through a capillary and a filter
      membrane coated with a collagen/platelet agonist. Termination of the CT is
      achieved when adhered and aggregated platelets of the passing blood flow occlude
      the membrane. Two PFA-100 test cartridges are used to measure the CT of citrated
      whole blood; either the collagen/ADP (PCA) or the collagen/ epinephrine (PCE). We
      investigated the applicability of the PFA-100 test system for quality control of
      platelet concentrates in comparison with platelet aggregometry. MATERIALS AND
      METHODS: For platelet aggregation, the combination of ADP (100 microM/l) and
      collagen (20 microg/ml) were used as agonists (ADP/COL). In our test system, 25
      microl epinephrine (10(-3) M) were added to the PCA cartridge (CT: PCAE) and 25
      microl ADP (100 microM/l) to the PCE cartridge (CT: PCEA), respectively. Red
      blood cells from a blood group 0 donor were adjusted to a hematocrit of 43% using
      platelet rich plasma (8 x 10(5)/microl) of the respective platelet concentrate.
      Fourteen irradiated and non-irradiated platelet concentrates were examined on
      days 0, 3 and 5 after platelet preparation. Swirling without a scoring system and
      mean platelet volume (MPV) were also tested. Statistical analyses were performed
      by Pearson's range coefficient, the Mann and Whitney test, and the Wilcoxon test.
      RESULTS: Swirling was seen in all platelet concentrates. Mean platelet volume was
      normal during the whole observation period like the PCAE in non-irradiated
      products. Only the PCAE showed finite CTs during the whole storage time.
      Consequently, further testing was performed exclusively with the PCAE. Weak but
      significant correlations could be found between the PCAE and ADP/COL (r = -0.53
      for non-irradiated platelet products, r = -0.62 for irradiated platelet products,
      p < or = 0.0001). Platelet function significantly decreased to around 60% of the
      initial value in the PCAE on day 5 of storage, ADP/COL decreased to 35% of
      maximum amplitude. A further decrease of approximately 10% was observed in the
      irradiated products, a fact which was significant in the PCAE. Only in the
      irradiated platelet products did MPV show a weak but significant correlation with
      the PCAE (r = 0.45, p = 0.002). CONCLUSION: Functional features of platelets from
      platelet concentrates characterized by ADP/COL induced aggregation can also be
      measured by the PFA-100. Yet, it has a higher sensitivity to platelet lesions
      induced by gamma-radiation. Further clinical studies will be necessary to
      determine whether PFA-measurements meet the quality criteria of MPV or swirling,
      or is superior in predicting in vivo viability. The relatively high cost of the
      test cartridge remains an obstacle for routine use.

PMID- 12509221
TI  - Hemapheresis listening post: apheresis certification.

PMID- 12509222
TI  - Protein A immunoadsorption in a pregnant woman with habitual abortion.
AB  - The role of antibodies in the occurrence of recurrent spontaneous miscarriage is
      well known. However there are many controversial issues in the management of
      habitual abortion. This paper describes the effect of Protein A immunoadsorption
      on serum levels of these antibodies and its impact on a case of a successfully
      treated woman in a outpatient department without need for a central venous
      catheter. Given the favourable clinical results described in our paper we think
      it may be relevant for some worse cases in clinical practice and will interest
      your readers.

PMID- 12509223
TI  - Src kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following
      VEGF stimulation of vascular endothelial cells.
AB  - BACKGROUND: The cytoplasmic tyrosine kinase, Src, has been found to play a
      crucial role in VEGF (vascular endothelial growth factor) - dependent vascular
      permeability involved in angiogenesis. The two main VEGFRs present on vascular
      endothelial cells are KDR/Flk-1 (kinase insert domain-containing receptor/fetal
      liver kinase-1) and Flt-1 (Fms-like tyrosine kinase-1). However, to date, it has
      not been determined which VEGF receptor (VEGFR) is involved in binding to and
      activating Src kinase following VEGF stimulation of the receptors. RESULTS: In
      this report, we demonstrate that Src preferentially associates with KDR/Flk-1
      rather than Flt-1 in human umbilical vein endothelial cells (HUVECs), and that
      VEGF stimulation resulted in an increase of Src activity associated with
      activated KDR/Flk-1. These findings were determined through immunoprecipitation
      kinase experiments and coimmunoprecipitation studies, and were further confirmed
      by GST-pull-down assays and Far Western studies. However, Fyn and Yes, unlike
      Src, were found to associate preferentially with Flt-1. CONCLUSIONS: Thus, Src
      preferentially associates with KDR/Flk-1, rather than with Flt-1, upon VEGF
      stimulation in endothelial cells. Our findings further highlight the potential
      significance of upregulated KDR/Flk-1-associated Src activity in the process of
      angiogenesis, and help to elucidate more clearly the specific roles and
      mechanisms involving Src family tyrosine kinase in VEGF-stimulated signal
      transduction events.

PMID- 12509224
TI  - Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1 is impaired
      by a somatic mutation found in kidney cancer.
AB  - Oxidative damage to mitochondrial DNA (mtDNA) has been implicated as a
      contributing factor to the origin of many pathological processes. Among the major
      DNA lesions generated by oxidative stress, 8-oxoguanine (8-oxoG) has a strong
      mutagenic potential. The main pathway for the repair of this lesion is the base
      excision repair (BER) initiated by the OGG1 DNA glycosylase. In human cells
      alternative splicing of the hOGG1 transcript yields two forms of the protein,
      alpha and beta, that are localised in the nucleus and the mitochondria,
      respectively. We describe here a hOGG1 somatic mutation, found in a kidney
      cancer, that modifies the intracellular localisation of beta-hOGG1. The glycine
      12 to glutamic acid substitution does not affect the enzymatic activity of the
      enzyme but lies in what was predicted to be a mitochondrial targeting sequence
      (MTS). Immunocytochemical localisation experiments show that the G12E mutant
      protein has diffuse cytoplasmic distribution instead of the mitochondrial
      localisation found for the wild-type, providing an example of a single amino acid
      substitution capable of disrupting a MTS. These results imply that these cancer
      cells are deficient in their mitochondrial 8-oxoG DNA repair activity.

PMID- 12509225
TI  - Alkylation resistance of E. coli cells expressing different isoforms of human
      alkyladenine DNA glycosylase (hAAG).
AB  - The alkyladenine DNA glycosylase (AAG) has been cloned from mouse and humans. AAG
      knock out mouse cells are sensitized to a variety of alkylating and cross-linking
      agents suggesting AAG is active on a variety of substrates. In humans, two
      isoforms have been characterized that are generated by alternative splicing and
      contain either exon 1a or 1b (hAAG1 or hAAG2). In this study, we examine the
      ability of the both known isoforms of human AAG (hAAG) to contribute to survival
      of Escherichia coli from treatments with simple alkylating agents and cross
      linking alkylating agents. Our results show that hAAG is effective at repairing
      methyl lesions when expressed in E. coli, but is unable to afford increased
      resistance to alkylating agents producing larger alkyl lesions such as ethyl
      lesions or lesions produced by the cross-linking alkylating agents N,N'-bis
      chloroethyl-N-nitrosourea (BCNU), N-(2-chloroethyl)-N-nitrosourea (CNU) or
      mitomycin C. In the case of CNU, expression of hAAG causes increased sensitivity
      rather than resistance, suggesting deleterious effects of hAAG activity. We also
      demonstrate that there are no apparent differences between the two isoforms of
      hAAG when recovery from damage produced by all alkylating agents is tested.

PMID- 12509226
TI  - A novel human DNA glycosylase that removes oxidative DNA damage and is homologous
      to Escherichia coli endonuclease VIII.
AB  - Prokaryotes and lower eukaryotes possess redundant activities that remove the
      plethora of oxidative DNA base damages produced during normal oxidative
      metabolism and which have been associated with cancer and aging. Thus far, only
      one oxidized pyrimidine-specific DNA glycosylase has been identified in humans,
      hNthl. Here, we report the identification of three new putative human DNA
      glycosylases that are phylogenetically members of the Fpg/Nei family primarily
      found in the bacterial kingdom. We have characterized one of these, hNEI1, and
      show it to be functionally homologous to bacterial Nei, that is, its principal
      substrates are oxidized pyrimidines, it undergoes a lyase reaction by, beta,delta
      elimination and traps a Schiff base with a substrate containing thymine glycol
      (Tg). Furthermore, inactivation of active site residues shown to be important in
      Escherichia coli Nei inactivate the human enzyme. The hNEI1 gene is located on
      the long arm of chromosome 15 that is frequently deleted in human cancers.

PMID- 12509227
TI  - Polymorphisms in the human xeroderma pigmentosum group A gene and their impact on
      cell survival and nucleotide excision repair.
AB  - Polymorphisms in DNA repair genes may contribute to defects in DNA repair and
      increased susceptibility to cancer. The xeroderma pigmentosum group A (XPA) gene
      is required for nucleotide excision repair (NER) and mutations in XPA highly
      predispose humans to skin cancer. We examined DNA samples from 189 individuals
      for polymorphisms in the XPA gene. First, SSCP analysis was used to examine each
      of the six exons and their intron boundaries. One frequent single nucleotide
      polymorphism (SNP) in the untranslated region of exon 1 and two rare SNPs which
      produce the changes Arg228Gln and Val234Leu in the coding region of exon 6 were
      identified. Quite surprisingly, no sequence variants were found within the coding
      regions or the adjacent intron boundaries of exons 1-5. Ecdysone-inducible
      expression vectors containing wild type XPA cDNA or cDNAs representing the two
      polymorphisms that we identified in exon 6 were created and independently
      introduced into the XPA deficient cell line XP12RO-SV. Transcription-coupled
      repair (TCR), global genome repair (GGR) and cell survival following UV
      irradiation were studied in each cell line in the absence or presence of the
      ecdysone hormone analog, ponasterone A. No substantial difference in repair or
      cell survival was found in cells complemented with wild type or polymorphic
      alleles of XPA. A 10-fold increase in the expression of XPA by addition of
      ponasterone A resulted in faster removal of 6-4 photoproducts from the total
      genomes of cells complemented with wild type or polymorphic alleles of XPA but
      had no significant impact on TCR or global genome repair of cyclobutane
      pyrimidine dimers (CPDs). Since our SSCP analysis failed to detect significant
      numbers of polymorphisms we directly sequenced exons 4-6 in a subset of our
      samples. One additional rare SNP, which produces the change Leu252Val was found
      in exon 6 and four rare SNPs and one rare single nucleotide deletion were found
      in intron 4. Hence, the XPA gene appears to be a cold spot for genetic variation
      and rare polymorphisms in the coding region of the gene do not reduce NER or cell
      survival after UV irradiation.

PMID- 12509228
TI  - Down-regulation of DNA repair synthesis at DNA single-strand interruptions in
      poly(ADP-ribose) polymerase-1 deficient murine cell extracts.
AB  - The functional involvement of poly(ADP-ribose) polymerase-1 (PARP-1) in the
      repair of DNA single- and double-strand breaks, DNA base damage, and related
      repair substrate intermediates remains unclear. Using an in vitro DNA repair
      assay and cell extracts derived from PARP-1 deficient or wild-type murine
      embryonic fibroblasts, we investigated the DNA synthesis and ligation steps
      associated with the rejoining of DNA single-strand interruptions containing 3'
      OH, and either 5'-OH or 5'-P termini. Complete repair leading to DNA rejoining
      was similar between PARP-1 deficient cells and wild-type controls and poly(ADP
      ribose) synthesis was, as expected, greatly reduced in PARP-1 deficient cell
      extracts. The incorporation of [32P]dCMP into repaired DNA at the site of a
      lesion was reduced two-three-fold in PARP-1 deficient cell extracts,
      demonstrating a decrease in repair patch size. Addition of purified PARP-1 to
      levels approximating those present in wild-type extracts did not stimulate DNA
      repair synthesis. We conclude that PARP-1 is not required for the efficient
      processing and rejoining of single-strand interruptions with defined 3'-OH and 5'
      OH or 5'-P termini. Decreased DNA repair synthesis observed in PARP-1 deficient
      cell extracts is associated with reduced cellular expression of several factors
      required for long-patch base excision repair (BER), including FEN-1 and DNA
      ligase I.

PMID- 12509229
TI  - Activities of human DNA polymerase kappa in response to the major benzo[a]pyrene
      DNA adduct: error-free lesion bypass and extension synthesis from opposite the
      lesion.
AB  - In cells, the major benzo[a]pyrene DNA adduct is the highly mutagenic (+)-trans
      anti-BPDE-N(2)-dG. In eukaryotes, little is known about lesion bypass of this DNA
      adduct during replication. Here, we show that purified human Polkappa can
      effectively bypass a template (+)-trans-anti-BPDE-N(2)-dG adduct in an error-free
      manner. Kinetic parameters indicate that Polkappa bypass of the (-)-trans-anti
      BPDE-N(2)-dG adduct was approximately 41-fold more efficient compared to the (+)
      trans-anti-BPDE-N(2)-dG adduct. Furthermore, we have found another activity of
      human Polkappa in response to the (+)- and (-)-trans-anti-BPDE-N(2)-dG adducts:
      extension synthesis from mispaired primer 3' ends opposite the lesion. In
      contrast, the two adducts strongly blocked DNA synthesis by the purified human
      Polbeta and the purified catalytic subunits of yeast Polalpha, Poldelta, and Pol
      epsilon right before the lesion. Extension by human Polkappa from the primer 3' G
      opposite the (+)- and (-)-trans-anti-BPDE-N(2)-dG adducts was mediated by a -1
      deletion mechanism, probably resulting from re-aligning the primer G to pair with
      the next template C by Polkappa prior to DNA synthesis. Thus, sequence contexts
      5' to the lesion strongly affect the fidelity and mechanism of the Polkappa
      catalyzed extension synthesis. These results support a dual-function model of
      human Polkappa in bypass of BPDE DNA adducts: it may function both as an error
      free bypass polymerase alone and an extension synthesis polymerase in combination
      with another polymerase.

PMID- 12509230
TI  - The oxidized pyrimidine ribonucleotide, 5-hydroxy-CTP, is hydrolyzed efficiently
      by the Escherichia coli recombinant Orf135 protein.
AB  - The Escherichia coli orf135 gene encodes a 15.4kDa protein with homology to the
      MutT family of nucleotide hydrolases. The orf135 gene was cloned within a
      glutathione S-transferase (GST) fusion protein expression vector, which was used
      to overproduce the GST-Orf135 fusion protein in E. coli. The fusion protein thus
      obtained was purified by affinity column chromatography and gel filtration
      chromatography from the crude extract. The recombinant Orf135 protein was
      obtained by removing the GST tag from the purified fusion protein. Various
      oxidized nucleotides were tested as substrates for the recombinant Orf135
      protein. As a result, we found a novel 5-hydroxy-CTPase activity of Orf135, but
      the hydrolyzing activities for the other nucleotides, including 5-hydroxy-dCTP,
      were very low. The activation constant (K(a)) of Mg(2+) for the 5-hydroxy-CTPase
      activity was 1.2 mM, and the pH optimum was 8.5. The catalytic efficiency
      (k(cat)/K(m)) for this activity was 630 s(-1) mM(-1) at 30 degrees C, which was
      30-fold higher than that for the CTPase activity. This result indicates that 5
      hydroxy-CTP is the best substrate of Orf135 among the nucleotides tested.

PMID- 12509231
TI  - Cellular roles of DNA polymerase zeta and Rev1 protein.
AB  - The majority of both spontaneous and DNA damage-induced mutations in eukaryotes
      result from replication processes in which DNA polymerase zeta (Polzeta) and Rev1
      protein (Rev1p) play major roles. Understanding these roles is likely to provide
      information relevant to the origin of genetic diseases, such as cancer, and may
      provide new insights for their prevention. DNA Polzeta also appears to be
      involved in the somatic hypermutability that occurs during development of the
      immune response. The results from a variety of genetic and enzymological
      investigations have started to delineate the cellular roles of these enzymes, but
      a number of important issues have not yet been resolved and much remains to be
      learned. Questions concerning the possible existence of other subunits to these
      enzymes, of their possible association with one another or with other proteins,
      of the nature of their enzymatic activities and of the relative roles played by
      these and other DNA polymerases in the bypass of different kinds of DNA damage,
      require further investigation. Finally, very little is known about the way these
      enzymes are regulated and brought into play when needed.

PMID- 12509232
TI  - Excision of 8-methylguanine site-specifically incorporated into oligonucleotide
      substrates by the AlkA protein of Escherichia coli.
AB  - 8-Methyl-2'-deoxyguanosine (8-medGuo) has been shown to be a major stable
      alkylation product of 2'-deoxyguanosine induced by methyl radical attack on DNA.
      Moreover, by using primer extension assays, the latter DNA modification has
      recently been reported to be a miscoding lesion by generating G to C and G to T
      transversions and deletions in vitro. However, no data have been reported up to
      now, concerning the processing of this C8-alkylated nucleoside by the DNA repair
      machinery. Therefore, we have investigated the capability of excision of 8
      methylguanine (8-meGua) site specifically incorporated into oligonucleotide
      substrates by several bacterial, yeast and mammalian DNA N-glycosylases. The
      results show that the 3-methyladenine (3-meAde) DNA glycosylase II (AlkA protein)
      from Escherichia coli is the only DNA N-glycosylase tested able to remove 8-meGua
      from double-stranded DNA fragments. Moreover, the activity of AlkA for 8-meGua
      varied markedly depending on the opposite base in DNA, being the highest with
      Adenine and Thymine and the lowest with Cytosine and Guanine. The removal of 8
      meGua by AlkA protein was compared to that of 7-methylguanine (7-meGua) and
      hypoxanthine (Hx). The rank of damage as a substrate for AlkA being 7-meGua>8
      meGua>Hx. In contrast, the human 3-meAde DNA N-glycosylase (Mpg) is not able to
      release 8-meGua paired with any of the four DNA bases. We also show that, DNA N
      glycosylases involved in the removal of oxidative damage, such as Fpg or Nth
      proteins from E. coli, Ntg1, Ntg2 or Ogg1 proteins of Saccharomyces cerevisiae,
      or human Ogg1 do not release 8-meGua placed opposite any of the four DNA bases.
      Furthermore, HeLa and Chinese hamster ovary (CHO) cell free protein extracts do
      not show any cleavage activity at 8-meGua paired with adenine or cytosine, which
      suggests the absence of base excision repair (BER) of this lesion in mammalian
      cells.

PMID- 12509233
TI  - The carboxy-terminal domain of the XPC protein plays a crucial role in nucleotide
      excision repair through interactions with transcription factor IIH.
AB  - The xeroderma pigmentosum group C (XPC) protein specifically involved in genome
      wide damage recognition for nucleotide excision repair (NER) was purified as a
      tight complex with HR23B, one of the two mammalian homologs of RAD23 in budding
      yeast. This XPC-HR23B complex exhibits strong binding affinity for single
      stranded DNA, as well as preferential binding to various types of damaged DNA. To
      examine the structure-function relationship of XPC, a series of truncated mutant
      proteins were generated and assayed for various binding activities. The two
      domains participating in binding to HR23B and damaged DNA, respectively, were
      mapped within the carboxy-terminal half of XPC, which also contains an
      evolutionary conserved amino acid sequence homologous to the yeast RAD4 protein.
      We established that the carboxy-terminal 125 amino acids are dispensable for both
      HR23B and damaged DNA binding, while interactions with transcription factor IIH
      (TFIIH) are significantly impaired by truncation of this domain. Furthermore,
      deletion of the extreme carboxy-terminal domain totally abolished XPC activity in
      the cell-free NER reaction. These results suggest that following initial damage
      recognition, the carboxy terminus of XPC may be essential for the recruitment of
      TFIIH, and that most truncation mutations identified in XP-C patients result in
      non-functional proteins.

PMID- 12509234
TI  - Inactivation of homologous recombination suppresses defects in topoisomerase III
      deficient mutants.
AB  - The Saccharomyces cerevisiae TOP3 gene encodes the type IA topoisomerase (Top3p)
      that is highly conserved in evolution. Deletion of TOP3 leads to a reduction in
      cell viability, hyper-recombination between repetitive DNA sequences, and
      abnormalities in both cell cycle progression and responses to DNA damaging
      agents. Deletion of SGS1, encoding the sole RecQ family helicase in S.
      cerevisiae, strongly suppresses the phenotypic effects of loss of TOP3 function.
      Here, we show that many of the adverse phenotypic effects of TOP3 deletion can
      also be partially alleviated by disruption of homologous recombination (HR)
      functions. This genetic interaction is seen both in strains deleted for TOP3 and
      in wild-type strains over-expressing a dominant-negative Top3p mutant form that
      confers a top3-like phenotype. Moreover, we show that this genetic interaction is
      conserved in the distantly-related fission yeast, Schizosaccharomyces pombe. Our
      results implicate topoisomerase III enzymes in recombination repair events
      required for cellular protection against DNA damaging agents and DNA replication
      inhibitors.

PMID- 12509235
TI  - Gamma-ray and hydrogen peroxide induction of gene amplification in hamster cells
      deficient in DNA double strand break repair.
AB  - To investigate the role of DNA double strand breaks (DSBs) and of their repair in
      gene amplification, we analyzed this process in the V3 Chinese hamster cell line
      and in the parental line AA8, after exposure to gamma-rays and to hydrogen
      peroxide (H2O2). V3 is defective in DSB repair because of a mutation in the DNA
      dependent protein kinase catalytic subunit (DNA-PKcs) gene, a gene involved in
      the non-homologous end-joining pathway. As a measure of gene amplification we
      used the frequency of colonies resistant to N-(phosphonacetyl)-L-aspartate
      (PALA), since in rodent cells PALA resistance is mainly achieved through the
      amplification of the CAD (carbamyl-P-synthetase, aspartate transcarbamylase,
      dihydro-orotase) gene. After treatment with different doses of gamma-rays and of
      H2O2, we found a dose related increase in the frequency of gene amplification and
      of chromosome aberrations. When the same doses of damaging agents were used,
      these increments were higher in V3 than in AA8. These results indicate that DSBs
      that are not efficiently repaired can be responsible for the induction of gene
      amplification. H2O2 stimulates gene amplification as well as gamma-rays, however,
      at similar levels of amplification induction, chromosome damage was about 50%
      lower. This suggests that gene amplification can be induced by H2O2 through
      pathways alternative to a direct DNA damage. Stimulation of gene amplification by
      H2O2, which is one of the products of the aerobic metabolism, supports the
      hypothesis that cellular metabolic products themselves can be a source of genome
      instability.

PMID- 12509237
TI  - Increased rOGG1 expression in regenerating rat liver tissue without a
      corresponding increase in incision activity.
AB  - Rapidly proliferating tissue with synthesis of a large number of cellular
      macromolecules including DNA, may require enhanced DNA repair capacity in order
      to avoid fixation of promutagenic DNA lesions to mutations. This hypothesis was
      addressed by assessing the incision activity and the mRNA level of the DNA repair
      protein rat 8-oxodeoxyguanosine glycosylase (rOGG1) as well as the level of the
      oxidative stress biomarker 8-oxodeoxyguanosine (8-oxodG) in rat liver tissue
      before and after partial hepatectomy. A five-fold increase in rOGG1 expression
      was found at 24h after PHx relative to the control levels. At 48h the rOGG1 mRNA
      levels were reduced to three-times the control values. The corresponding incision
      activities of rOGG1 in the crude tissue extract as measured by the incision assay
      were slightly increased both at 24 and 48h after partial hepatectomy although the
      changes failed to be statistically significant (P=0.07 and 0.06, respectively).
      The levels of 8-oxodG were unaltered at 24h but increased to 1.8 times the
      control values at 48h after partial hepatectomy. The study showed that rapid
      proliferating liver tissue in vivo had an increased expression of the DNA repair
      protein rOGG1, without significantly increased incision activity on a 8-oxodG
      containing substrate and with unchanged levels of 8-oxodG/10(6) dGuo after 24h of
      regeneration. At 48h the rOGG1 expression was decreased, and the levels of 8
      oxodG/10(6) dGuo increased but still significant changes in the incision activity
      could not be detected. Thus, we can conclude that the rOGG1 expression is
      temporarily up-regulated by the proliferating events elicited by partial
      hepatectomy.

PMID- 12509238
TI  - Mouse mutant database relevant to cellular responses to DNA damage.

PMID- 12509239
TI  - Structure-based interpretation of missense mutations in Y-family DNA polymerases
      and their implications for polymerase function and lesion bypass.
AB  - Our understanding of the molecular mechanisms of error-prone lesion bypass has
      changed dramatically in the past few years. The concept that the key participants
      in the mutagenic process were accessory proteins that somehow modified the
      ability of the cell's main replicase to facilitate bypass of normally blocking
      lesions has been replaced with one in which the replicase is displaced by a
      polymerase specialized in lesion bypass. The participants in this process remain
      the same, only their function has been reassigned. What was once known as the
      UmuC/DinB/Rev1/Rad30 superfamily of mutagenesis proteins, is now known as the Y
      family of DNA polymerases. Quite remarkably, within the space of 3 years, the
      field has advanced from the initial discovery of intrinsic polymerase function,
      to the determination of the tertiary structures of several Y-family DNA
      polymerases.A key to determining the biochemical properties of each DNA
      polymerase is through structure-function studies that result in the site-specific
      substitution of particular amino acids at critical sites within each DNA
      polymerase. However, we should not forget the power of genetic selection that
      allows us to identify residues within each polymerase that are generated by
      "random mutagenesis" and which are important for both a gain or loss of function
      in vivo. In this review, we discuss the structural ramifications of several
      missense mutations previously identified in various Y-family DNA polymerase and
      speculate on how each amino acid substitution might modify the enzymatic activity
      of the respective polymerase or possibly perturb protein-protein interactions
      necessary for efficient translesion replication in vivo.

PMID- 12509240
TI  - Molecular characterization and developmental expression of the TFIIH factor p62
      gene from Drosophila melanogaster: effects on the UV light sensitivity of a p62
      mutant fly.
AB  - TFIIH is a multiprotein complex that has a central role in the RNA pol II
      mediated transcription, in DNA repair and in the control of the cell cycle.
      Mutations in some components of TFIIH are associated with three hereditary human
      syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and
      trichothiodystrophy (TTD). The p62 protein is a structural component of the TFIIH
      core and no syndromes have been identified up to date by mutations in this human
      gene. In this work we report the molecular and genetic characterization of the
      Drosophila melanogaster p62 gene (Dmp62). The Dmp62 gene product shows high
      identity with its human and mouse homologues. Using computer analysis we
      identified several common motifs in the p62 proteins from different organisms,
      suggesting that these motifs could be involved in possible protein-protein
      interactions within the TFIIH complex or with other transcription and DNA repair
      factors. The Dmp62 transcript is expressed at similar levels throughout
      development, although there is a significant increase of the transcript level
      during the late embryogenesis and in the adult male. The analysis of a Drosophila
      line with a P-element enhancer trap insertion at the Dmp62 5'-UTR that directs
      the lac-Z expression from the Dmp62 promoter, showed a high level of expression
      in the gut, the testis and the pericardial cells. A P-element that disrupts the
      Dmp62 gene (Dmp62mut) produces early embryo lethality in homozygous flies.
      Heterozygous Dmp62mut larvae are more sensitive to UV light irradiation, and
      those individuals that are able to develop into adults have severe abdominal
      cuticular damage after UV light irradiation.

PMID- 12509241
TI  - Mutagenic fingerprint of ozone in human cells.
AB  - Ozone is an important factor in urban pollution and represents a major concern
      for human health. The chemical reactivity of ozone toward biological targets and
      particularly its genotoxicity supports a possible link between exposure and
      cancer risk, but no molecular data exist on its mutagenic potential in human
      cells. Using a shuttle vector, we showed that ozone is indeed a potent mutagen
      and we characterized the mutation spectrum it produced in human cells. Almost all
      mutations are base substitutions, essentially located at G:Cs (75%), typical of
      reactive oxygen species (ROS), but occurring in a specific pattern, i.e. a
      similar extent of GC:TA (28%), GC:CG (23%) and GC:AT (23%). The targeted
      distribution of mutations and identification of hotspot sequences define the
      first molecular fingerprint of mutations induced by ozone in human cells.
      Possible applications derived from our results with respect to ozone genotoxicity
      should help determining quantifiable biomarkers of ozone exposure in human
      health, especially for carcinogenesis.

PMID- 12509242
TI  - Translation of hSNM1 is mediated by an internal ribosome entry site that
      upregulates expression during mitosis.
AB  - SNM1 is involved in the repair of DNA interstrand cross-links (ICLs) in
      Saccharomyces cerevisiae and possibly in human cells, although relatively little
      is known about its biochemical function. The hSNM1 contains a long 5'
      untranslated region (5'UTR) predicted to fold into a complex secondary structure,
      and which contains numerous short open reading frames (ORFs). We show here using
      bicistronic constructs that human SNM1 mRNA contains an internal ribosome entry
      site (IRES) that generally suppresses translation, except during mitosis where
      translation is upregulated. These results suggest that hSNM1 may have a mitotic
      function possibly involved in response to DNA interstrand cross-linking agents.

PMID- 12509243
TI  - Fold-recognition analysis predicts that the Tag protein family shares a common
      domain with the helix-hairpin-helix DNA glycosylases.
AB  - The Escherichia coli protein Tag is traditionally regarded as an archetype of one
      of four classes of N-alkylpurine DNA glycosylases. However, its structure and
      phylogenetic relationship to other glycosylases remains a mystery. Fold
      recognition and sequence profile analyses suggest that Tag shares the catalytic
      domain with helix-hairpin-helix (HhH) glycosylases such as MutY, AlkA and
      EndoIII, but its N- and C-termini together form a unique His2Cys2 cluster. The
      findings presented in this paper provide insight into sequence-structure-function
      relationships in the Tag family and should aid in a more precise definition of
      the common core of the HhH superfamily of glycosylases involved in DNA repair.

PMID- 12509244
TI  - Joining of DNA ends bearing non-matching 3'-overhangs.
AB  - Using the Xenopus egg extract as an in vitro system for double strand break
      repair, the joining of DNA ends bearing non-complementary, homopolymeric, 4nt 3'
      protruding single strands ("overhangs") was examined. Such 3'-overhangs can not
      be filled-in and cannot align and anneal by canonical base pair interactions,
      thus presenting a special challenge to the repair machinery. The results indicate
      that two such non-matching 3'-overhangs typically overlap by 2nt forming non
      canonical base pairs, from which the filling-in of the remaining gaps is primed.
      The repair reaction is inhibited in Ku-depleted extracts. Unexpectedly, with some
      of the substrates the predominant repair products were joints with no nucleotide
      loss, suggesting that the two DNA ends aligned without overlap. However, the
      additional finding that an activity in the egg extract adds one or a few
      nucleotides to a fraction of the 3'-ends favors a model in which most or all of
      the zero-loss joints are the net result of 3'-overhang extension and 2bp overlap
      formation. The nucleotide addition reaction is stimulated by increasing the
      concentration of the complementary dNTP or ddNTP in the extract, suggesting a
      process templated by free nucleotides and the involvement of a DNA polymerase
      like activity.

PMID- 12509245
TI  - Repair of 8-oxoG is slower in endogenous nuclear genes than in mitochondrial DNA
      and is without strand bias.
AB  - DNA is vulnerable to the attack of certain oxygen radicals and one of the major
      DNA lesions formed is 7,8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic
      lesion that can mispair with adenine. The repair of 8-oxoG was studied by
      measuring the gene specific removal of 8-oxoG after treatment of Chinese hamster
      ovary (CHO) fibroblasts with the photosensitizer Ro19-8022. This compound
      introduces 8-oxoG lesions, which can then be detected with the Escherichia coli
      formamidopyrimidine DNA glycosylase (FPG). In this report we present gene
      specific repair analysis of endogenous genes situated in different important
      cellular regions and also the first analysis of strand specific DNA repair of 8
      oxoG in an endogenous gene. We were not able to detect any preferential repair of
      transcribed genes compared to non-transcribed regions and we did not detect any
      strand-bias in the repair of the housekeeping gene, dihydrofolate reductase
      (DHFR). In vivo, mitochondrial DNA is highly exposed to reactive oxygen species
      (ROS), and we find that the repair of 8-oxoG is more efficient in the
      mitochondrial DNA than in the nuclear DNA.

PMID- 12509246
TI  - Ambiguous coding is required for the lethal interaction between methylated DNA
      bases and DNA mismatch repair.
AB  - The thiopurine 6-thioguanine (S6G) is used to treat acute leukaemia. Its
      cytotoxic effect requires an active DNA mismatch repair (MMR) system. S6G is
      incorporated into DNA where a small fraction undergoes in situ conversion to S6
      thiomethylguanine (S6meG). After replication, S6meG-containing base pairs
      interact with MMR. This interaction is ultimately lethal and MMR-defective cells
      are resistant to S6G. Here, we report that growing human cells extensively
      incorporate the thiopyrimidine nucleoside 4-thiothymidine (S4TdR) into their DNA.
      The incorporated thiopyrimidine (S4T) can also undergo facile S-methylation to 4
      thiomethylthymine (S4meT). The rate of methylation of S4TdR in model substrates
      is similar to that for the conversion of S6G to S6meG indicating that the DNA of
      cells grown in S4TdR will contain significant levels of S4meT. Despite this,
      S4TdR is not associated with MMR-related cell death. We demonstrate that, in
      contrast to S6meG, neither DNA S4T nor S4meT codes ambiguously. S4T retains the
      coding properties of unmodified T, whereas S4meT behaves like a normal cytosine
      and exclusively directs the incorporation of guanine. The preferred S4meT:G base
      pair is also a poor substrate for binding by the hMutSalpha mismatch recognition
      factor. We suggest that the ability of S4meT to produce a structurally acceptable
      base pair during replication underlies the absence of MMR-related death in cells
      treated with S4TdR.

PMID- 12509247
TI  - HSM2 (HMO1) gene participates in mutagenesis control in yeast Saccharomyces
      cerevisiae.
AB  - We have previously reported about a new Saccharomyces cerevisiae mutation, hsm2
      1, that results in increase of both spontaneous and UV-induced mutation
      frequencies but does not alter UV-sensitivity. Now HSM2 gene has been genetically
      and physically mapped and identified as a gene previously characterized as HMO1,
      a yeast homologue of human high mobility group genes HMG1/2. We found that hsm2
      mutant is slightly deficient in plasmid-borne mismatch repair. We tested UV
      induced mutagenesis in double mutants carrying hsm2-1 mutation and a mutation in
      a gene of principal damaged DNA repair pathways (rad2 and rev3) or in a mismatch
      repair gene (pms1 and recently characterized in our laboratory hsm3). The
      frequency of UV-induced mutations in hsm2 rev3 was not altered in comparison with
      single rev3 mutant. In contrast, the interaction of hsm2-1 with rad2 and pms1 was
      characterized by an increased frequency of UV-induced mutations in comparison
      with single rad2 and pms1 mutants. The UV-induced mutation frequency in double
      hsm2 hsm3 mutant was lower than in the single hsm2 and hsm3 mutants. The role of
      the HSM2 gene product in control of mutagenesis is discussed.

PMID- 12509248
TI  - Suppression of a DNA double-strand break repair gene, Ku70, increases radio- and
      chemosensitivity in a human lung carcinoma cell line.
AB  - Ku70 protein, cooperating with Ku80 and DNA-dependent protein kinase (DNA-PK)
      catalytic subunit (DNA-PKcs), is involved in DNA double-strand break (DNA DSB)
      repair and V(D)J recombination. Recent studies have revealed increased ionizing
      radiosensitivity in Ku70-deficient cells. The presented study, using a human
      squamous cell lung carcinoma cell line, demonstrated that introduction of an
      antisense Ku70 nucleic acid made the cells more radio- and chemosensitive than
      the parental cells. Ku70 protein expression was suppressed in the cells with
      antisense Ku70 construct when compared to the wild-type cells. A relatively small
      but statistically significant increase in radiosensitivity of the cells was
      achieved by the introduction of the antisense Ku70. The increased
      radiosensitivity in vitro was accompanied by an approximately two-fold increase
      in alpha and alpha/beta values in a linear-quadratic model. The antisense Ku70
      increased the chemosensitivity of the cells to some DNA-damaging agents such as
      bleomycin and methyl methanesulfonate, but not to cisplatin, mitomycin C, and
      paclitaxel. This system provides us with partial suppression of Ku70, and will be
      a useful experimental model for investigating the physiological roles of the DNA
      DSB repair gene.

PMID- 12509249
TI  - Epistatic analysis of the roles of the RAD27 and POL4 gene products in DNA base
      excision repair in S. cerevisiae.
AB  - The cellular role of the DNA polymerase encoded by the Saccharomyces cerevisiae
      POL4 gene is unclear. We have used an epistasis analysis to investigate whether
      the proteins encoded by the POL4 and RAD27 genes participate in alternative, non
      redundant subpathways of DNA base excision repair (BER). We constructed strains
      in which the genes were deleted singly or in combination and have examined their
      sensitivity to DNA damaging agents as well as spontaneous mutation frequency. The
      double deletion strain is no more sensitive to damaging agents and has no higher
      spontaneous mutation frequency than the most sensitive single mutant. These data
      indicate that the protein encoded by the POL4 gene does not participate in a non
      redundant subpathway of base excision repair under these conditions. We discuss
      the implications of these results in light of the recent classification of the
      POL4 gene product as a member of the DNA polymerase lambda family.

PMID- 12509250
TI  - Involvement of DNA polymerase beta in protection against the cytotoxicity of
      oxidative DNA damage.
AB  - We had shown previously that DNA polymerase beta (beta-pol) null mouse
      fibroblasts, deficient in base excision repair (BER), are hypersensitive to
      monofunctional methylating agents but not to hydrogen peroxide (H2O2). This is
      surprising because beta-pol is thought to be involved in BER of oxidative as well
      as methylated DNA damage. We confirm these findings here in early-passage cells.
      However, with time in culture, beta-pol null cells become hypersensitive to H2O2
      and other reactive oxygen species-generating agents. Analysis of in vitro BER
      reveals a strong deficiency in single-nucleotide BER of 8-oxoguanine (8-oxoG) by
      both early- and late-passage beta-pol null cell extracts. Therefore, in early
      passage wild-type and beta-pol null cells, the capacity for single-nucleotide BER
      of 8-oxoG does not correlate with cellular sensitivity to H2O2. Expression of
      beta-pol protein in the late-passage null cells almost completely reverses the
      H2O2-hypersensitivity phenotype. Methoxyamine (MX) treatment sensitizes late
      passage wild-type cells to H2O2 as expected for beta-pol-mediated single
      nucleotide BER; however in beta-pol null cells, MX has no effect. The data
      indicate a role(s) of beta-pol-dependent repair in protection against the
      cytotoxicity of oxidative DNA damage in wild-type cells.

PMID- 12509251
TI  - The formation of UV-induced chromosome aberrations involves ERCC1 and XPF but not
      other nucleotide excision repair genes.
AB  - ERCC1-XPF, through its role in nucleotide excision repair (NER), is essential for
      the repair of DNA damage caused by UV light. ERCC1-XPF is also involved in
      recombinational repair processes distinct from NER. In rodent cells chromosome
      aberrations are a common consequence of UV irradiation. We have previously shown
      that ERCC1-deficient cells have a lower ratio of chromatid exchanges to breaks
      than wild type cells. We have now confirmed this result and have shown that XPF
      deficient cells also have a lower ratio than wild type. However, cells deficient
      in the other NER genes, XPD, XPB and XPG, all have the same ratio of exchanges to
      breaks as wild type. This implies that ERCC1-XPF, but not other NER proteins, is
      involved in the formation of UV-induced chromosome aberrations, presumably
      through the role of ERCC1-XPF in recombinational repair pathways rather than NER.
      We suggest that ERCC1-XPF may be involved in the bypass/repair of DNA damage in
      replicating DNA by an exchange mechanism involving single strand annealing
      between non-homologous chromosomes. This mechanism would rely on the ability of
      ERCC1-XPF to trim non-homologous 3' tails.

PMID- 12509252
TI  - Defending genome integrity during S-phase: putative roles for RecQ helicases and
      topoisomerase III.
AB  - The maintenance of genome stability is important not only for cell viability, but
      also for the suppression of neoplastic transformation in higher eukaryotes. It
      has long been recognised that a common feature of cancer cells is genomic
      instability. Although the so-called three 'Rs' of genome maintenance, DNA
      replication, recombination and repair, have historically been studied in
      isolation, a wealth of recent evidence indicates that these processes are
      intimately interrelated and interdependent. In this article, we will focus on
      challenges to the maintenance of genome integrity that arise during the S-phase
      of the cell cycle, and the possible roles that RecQ helicases and topoisomerase
      III play in the maintenance of genome integrity during the process of DNA
      replication.

PMID- 12509253
TI  - Transcription coupled repair efficiency determines the cell cycle progression and
      apoptosis after UV exposure in hamster cells.
AB  - Nucleotide excision repair (NER) is a major pathway for the removal of bulky
      adducts and helix distorting lesions from the genomic DNA. NER is highly
      heterogeneous across the genome and operates principally at different levels of
      hierarchy. Transcription coupled repair (TCR), a special sub-pathway of NER and
      base excision repair (BER), is critical for cellular resistance after UV
      irradiation in mammalian cells. In this study, we have investigated the effects
      of UV-C irradiation on cell cycle progression and apoptosis in G1 synchronised
      isogenic hamster cell lines that are deficient in TCR and NER pathways. Our
      results revealed the existence of two apoptotic modes at low UV (2-4J/m2) doses
      in TCR deficient (UV61) and NER deficient (UV5) cells: one occurring in the first
      G1 and the other in the second G1-phase following the first division. At high UV
      doses (8-32J/m2), UV61 and UV5 cells underwent apoptosis without entry into S
      phase after a permanent arrest in the initial G1. In contrast to repair deficient
      cells, parental TCR proficient AA8 cells did not show a significant G1 arrest and
      apoptosis at doses below 8J/m2. UV61 (proficient in repair of 6-4 photoproducts
      (PPs)) and UV5 (deficient in 6-4 PP repair) cells showed similar patterns of cell
      cycle progression and apoptosis. Taken together, these results suggest that the
      persistence of 6-4 PP and the replication inhibition may not be critical for
      apoptotic response in hamster cells. Instead, the extent of transcription
      blockage resulting from the TCR deficiency constitutes the major determining
      factor for G1 arrest and apoptosis.

PMID- 12509254
TI  - Defining interactions between DNA-PK and ligase IV/XRCC4.
AB  - Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double
      strand breaks (DSBs) in mammalian cells. DNA-dependent protein kinase (DNA-PK),
      ligase IV, and XRCC4 are all critical components of the NHEJ repair pathway. DNA
      PK is composed of a heterodimeric DNA-binding component, Ku, and a large
      catalytic subunit, DNA-PKcs. Ligase IV and XRCC4 associate to form a multimeric
      complex that is also essential for NHEJ. DNA-PK and ligase IV/XRCC4 interact at
      DNA termini which results in stimulated ligase activity. Here, we define
      interactions between the components of these two essential complexes, DNA-PK and
      ligase IV/XRCC4. We find that ligase IV/XRCC4 associates with DNA-PK in a DNA
      independent manner. The specific protein-protein interactions that mediate the
      interaction between these two complexes are further identified. Direct
      interactions between ligase IV and Ku as well as between XRCC4 and DNA-PKcs are
      shown. In contrast, binding of ligase IV to DNA-PKcs or XRCC4 to Ku is very weak
      or non-existent. Our data defines the specific protein pairs involved in the
      association of DNA-PK and ligase IV/XRCC4, and suggests a molecular mechanism for
      coordinating the assembly of the DNA repair complex at DNA breaks.

PMID- 12509255
TI  - DNA repair capacity after gamma-irradiation and expression profiles of DNA repair
      genes in resting and proliferating human peripheral blood lymphocytes.
AB  - DNA repair plays an important role in maintaining genomic integrity, and
      deficiencies in repair function are known to promote cancer development. Several
      studies have used the individual capacity to repair DNA damage in peripheral
      blood lymphocytes (PBLs) as a cancer risk marker. As the cell's ability to remove
      DNA damage may be correlated with proliferative activity, it is an important
      question whether quiescent or dividing cells should be used in such studies. The
      aim of our study was to compare DNA repair capacity and expression profiles of 70
      known DNA repair genes, both in resting and phytohemagglutinin (PHA) stimulated
      human PBLs. Using the comet assay, gamma-radiation-induced DNA damage and repair
      in lymphocytes was analyzed. No difference, neither in the rate of radiation
      induced DNA damage nor in DNA repair capacity between PHA-stimulated and non
      stimulated PBLs was observed. Stimulated cells, however, showed significantly
      elevated values for background damage. Transcriptional profiles of repair genes
      were analyzed using cDNA arrays. Hybridization experiments were performed with
      mRNA isolated from both unstimulated and PHA-stimulated PBLs. More than 70% of
      all evaluated genes had constant expression levels. Twelve genes responded with a
      more than two-fold increase of transcripts to the mitogenic stimulus. Most of the
      up-regulated repair enzymes are also known to play a role in DNA replication. In
      conclusion, the data presented here suggest that all repair proteins needed for
      the repair of gamma-irradiation induced DNA-damage, that can be detected by the
      alkaline comet assay, are already present in G0 cells at sufficient amounts and
      do not need to be induced once lymphocytes are stimulated to start cycling. Our
      results thus do not support a general increase in DNA repair activity of PBLs by
      PHA stimulation, and the use of stimulated PBLs in molecular epidemiological
      studies on DNA repair of gamma-irradiation induced DNA damage seems not to be
      mandatory.

PMID- 12509256
TI  - Opposite base specificity in excision of pyrimidine ring-opened 1,N6
      ethenoadenine by thymine glycol-DNA-glycosylases.
AB  - A highly mutagenic DNA lesion, 1,N6-ethenoadenine ( epsilon A) is chemically
      unstable and either depurinates or converts to a pyrimidine ring-opened product
      upon water molecule addition to the C(2)z.sbnd;N(3) bond in epsilon dA (compound
      B). Compound B subsequently undergoes deformylation to yield compound C, which
      depurinates in the final step of the epsilon A rearrangement pathway. We have
      previously shown that epsilon A rearrangement products are not repaired by human
      N-methylpurine-DNA-glycosylase, which excises parental epsilon A. Compound B was
      shown to be eliminated from a B:T pair by Escherichia coli formamidopyrimidine
      DNA-glycosylase (Fpg protein) and endonuclease III (Nth protein). Fpg protein
      excised B also from a B:C pair, and much less efficiently from B:A and B:G pairs
      [J. Biol. Chem. 276 (2001) 21821]. Here we show that efficiency of B excision by
      the Nth protein also depends on the opposite base in the pair. Most efficient
      repair is observed when this derivative is paired with dG (Km=18nM, kcat=12) and
      is less favourable when paired with dC (Km=40nM, kcat=13) and dT (Km=32nM,
      kcat=11). In physiological conditions, compound B is probably not excised by the
      Nth-glycosylase from a B:A pair, or from a single-stranded DNA, since kinetic
      constants in these conditions are an order or two orders of magnitude higher than
      when B is paired with T, C or G. A similar specificity for B excision was found
      for Saccharomyces cerevisiae Ntg2-glycosylase. Thus, when paired with A, an
      epsilon A derivative might be more persistent than when paired with other bases
      and give rise to AT-->TA transversions.

PMID- 12509257
TI  - Mutagenesis in the spotlight.

PMID- 12509258
TI  - In pursuit of a molecular mechanism for adaptive gene amplification.
AB  - "Adaptive" or "stationary-phase" mutation is a collection of apparent stress
      responses in which cells exposed to a growth-limiting environment generate
      genetic changes, some of which can allow resumption of rapid growth. In the well
      characterized Lac system of Escherichia coli, reversions of a lac frameshift
      allele give rise to adaptive point mutations. Also in this system, adaptive gene
      amplification has been documented as a separate and parallel response that allows
      growth on lactose medium without acquisition of a compensatory frameshift
      mutation. In amplification, the DNA region containing the weakly functional lac
      allele becomes amplified to multiple copies, which produce sufficient enzyme
      activity to allow growth on the otherwise growth-limiting lactose medium. The
      amplifications are "adaptive" in that they occur after cells encounter the growth
      limiting environment. Adaptive amplification is a reversible genetic change that
      allows adaptation and growth. It may be similar to chromosomal instability
      observed in the origins and progression of many cancers. We explore possible
      molecular mechanisms of adaptive amplification in the bacterial system and note
      parallels to chromosomal instability in other systems.

PMID- 12509259
TI  - The "A" rule revisited: polymerases as determinants of mutational specificity.
AB  - Organisms control the specificity and frequency with which they mutate via their
      complement of proteins. The mismatch repair (MMR) proteins correct errors after
      they are made. The DNA polymerases of the cell determine the response to damaged
      DNA which has not been repaired by excision. Polymerase action can be considered
      as consisting of three main steps: addition of a base, proofreading of the added
      nucleotide and elongation. Each of these steps is kinetically complex and can be
      modulated. The modulation accounts for different behaviors of organisms in
      response to stress. The recent findings of DNA polymerases with properties
      appropriate for dealing with damaged DNA may help to account for the phenomenon
      of spontaneous mutation and for the hypermutability associated with
      immunoglobulin maturation and carcinogenesis.

PMID- 12509260
TI  - Arsenic-induced Mre11 phosphorylation is cell cycle-dependent and defective in
      NBS cells.
AB  - Cancer-prone diseases ataxia-telangiectasia (AT), Nijmegen breakage syndrome
      (NBS) and ataxia-telangiectasia-like disorder (ATLD) are defective in the repair
      of DNA double-stranded break (DSB). On the other hand, arsenic (As) has been
      reported to cause DSB and to be involved in the occurrence of skin, lung and
      bladder cancers. To dissect the repair mechanism of As-induced DSB, wild type, AT
      and NBS cells were treated with sodium arsenite to study the complex formation
      and post-translational modification of Rad50/NBS1/Mre11 repair proteins. Our
      results showed that Mre11 went through cell cycle-dependent phosphorylation upon
      sodium arsenite treatment and this post-translational modification required NBS1
      but not ATM. Defective As-induced Mre11 phosphorylation was rescued by
      reconstitution with full length NBS1 in NBS cells. Although As-induced Mre11
      phosphorylation was not required for Rad50/NBS1/Mre11 complex formation, it might
      be required for the formation of Rad50/NBS1/Mre11 nuclear foci upon DNA damage.

PMID- 12509261
TI  - UVB radiation-induced cancer predisposition in Cockayne syndrome group A (Csa)
      mutant mice.
AB  - Cockayne syndrome (CS) is an inherited photosensitive neurodevelopmental disorder
      caused by a specific defect in the transcription-coupled repair (TCR) sub-pathway
      of NER. Remarkably, despite their DNA repair deficiency, CS patients do not
      develop skin cancer. Here, we present a mouse model for CS complementation group
      A. Like cells from CS-A patients, Csa-/- mouse embryonic fibroblasts (MEFs): (i)
      are ultraviolet (UV)-sensitive; (ii) show normal unscheduled DNA synthesis
      (indicating that the global genome repair sub-pathway is unaffected); (iii) fail
      to resume RNA synthesis after UV-exposure and (iv) are unable to remove
      cyclobutane pyrimidine dimers (CPD) photolesions from the transcribed strand of
      active genes. CS-A mice exhibit UV-sensitivity and pronounced age-dependent loss
      of retinal photoreceptor cells but otherwise fail to show the severe
      developmental and neurological abnormalities of the human syndrome. In contrast
      to human CS, Csa-/- animals develop skin tumors after chronic exposure to UV
      light, indicating that TCR in mice protects from UV-induced skin cancer
      development. Strikingly, inactivation of one Xpc allele (encoding a component of
      the damage recognition complex involved in the global genome repair sub-pathway)
      in Csa-/- mice resulted in a strongly enhanced UV-mediated skin cancer
      sensitivity, indicating that in a TC repair defective background, the Xpc gene
      product may be a rate-limiting factor in the removal of UV-induced DNA lesions.

PMID- 12509262
TI  - Genetics of mutagenesis in E. coli: various combinations of translesion
      polymerases (Pol II, IV and V) deal with lesion/sequence context diversity.
AB  - The biochemistry and genetics of translesion synthesis (TLS) and, as a
      consequence, of mutagenesis has recently received much attention in view of the
      discovery of novel DNA polymerases, most of which belong to the Y family. These
      distributive and low fidelity enzymes assist the progression of the high fidelity
      replication complex in the bypass of DNA lesions that normally hinder its
      progression. The present paper extends our previous observation that in
      Escherichia coli all three SOS-inducible DNA polymerases (Pol II, IV and V) are
      involved in TLS and mutagenesis. The genetic control of frameshift mutation
      pathways induced by N-2-acetylaminofluorene (AAF) adducts or by oxidative lesions
      induced by methylene blue and visible light is investigated. The data show
      various examples of mutation pathways with an absolute requirement for a specific
      combination of DNA polymerases and, in contrast, other examples where two DNA
      polymerases exhibit functional redundancy within the same pathway. We suggest
      that cells respond to the challenge of replicating DNA templates potentially
      containing a large diversity of DNA lesions by using a pool of accessory DNA
      polymerases with relaxed specificities that assist the high fidelity replicase.

PMID- 12509263
TI  - Reflections on the 8th international conference on environmental mutagens.

PMID- 12509264
TI  - Suppression of high-fidelity double-strand break repair in mammalian chromosomes
      by pifithrin-alpha, a chemical inhibitor of p53.
AB  - We investigated the effect of pifithrin-alpha (PFTalpha), a chemical inhibitor of
      p53, on DNA double-strand break (DSB) repair in mammalian chromosomes. Thymidine
      kinase-deficient mouse fibroblasts were stably transfected with DNA substrates
      containing one or two recognition sites for yeast endonuclease I-SceI embedded
      within a herpes simplex virus thymidine kinase gene. Genomic DSBs were induced by
      introducing an I-SceI expression plasmid into cells in the presence or absence of
      20 microM PFTalpha. From cells containing the DNA substrate with a single I-SceI
      site we recovered low-fidelity nonhomologous end-joining (NHEJ) events in which
      one or more nucleotides were deleted or inserted at the DSB. From cells
      containing the substrate with two I-SceI sites we recovered high-fidelity DNA end
      joining (precise ligation (PL)) events. We found that treatment of cells with
      PFTalpha caused a 5-10-fold decrease in recovery of PL but decreased recovery of
      NHEJ by less than two-fold. Deletion sizes associated with NHEJ were unaffected
      by treatment with PFTalpha. Our work suggests the possibility that p53
      facilitates high-fidelity DSB repair while playing little or no role in mutagenic
      NHEJ.

PMID- 12509265
TI  - Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice.
AB  - Mutations in the CSB gene cause Cockayne syndrome (CS), a rare inherited
      disorder, characterized by UV-sensitivity, severe neurodevelopmental and
      progeroid symptoms. CSB functions in the transcription-coupled repair (TCR) sub
      pathway of nucleotide excision repair (NER), responsible for the removal of UV
      induced and other helix-distorting lesions from the transcribed strand of active
      genes. Several lines of evidence support the notion that the CSB TCR defect
      extends to other non-NER type transcription-blocking lesions, notably various
      kinds of oxidative damage, which may provide an explanation for part of the
      severe CS phenotype. We used genetically defined mouse models to examine the
      relationship between the CSB defect and sensitivity to oxidative damage in
      different cell types and at the level of the intact organism. The main
      conclusions are: (1) CSB(-/-) mouse embryo fibroblasts (MEFs) exhibit a clear
      hypersensitivity to ionizing radiation, extending the findings in genetically
      heterogeneous human CSB fibroblasts to another species. (2) CSB(-/-) MEFs are
      highly sensitive to paraquat, strongly indicating that the increased cytotoxicity
      is due to oxidative damage. (3) The hypersenstivity is independent of genetic
      background and directly related to the CSB defect and is not observed in totally
      NER-deficient XPA MEFs. (4) Wild type embryonic stem (ES) cells display an
      increased sensitivity to ionizing radiation compared to fibroblasts.
      Surprisingly, the CSB deficiency has only a very minor additional effect on ES
      cell sensitivity to oxidative damage and is comparable to that of an XPA defect,
      indicating cell type-specific differences in the contribution of TCR and NER to
      cellular survival. (5) Similar to ES cells, CSB and XPA mice both display a minor
      sensitivity to whole-body X-ray exposure. This suggests that the response of an
      intact organism to radiation is largely determined by the sensitivity of stem
      cells, rather than differentiated cells. These findings establish the role of
      transcription-coupled repair in resistance to oxidative damage and reveal a cell-
      and organ-specific impact of this repair pathway to the clinical phenotype of CS
      and XP.

PMID- 12509266
TI  - Hypersensitivity of DNA polymerase beta null mouse fibroblasts reflects
      accumulation of cytotoxic repair intermediates from site-specific alkyl DNA
      lesions.
AB  - Monofunctional alkylating agents react with DNA by S(N)1 or S(N)2 mechanisms
      resulting in formation of a wide spectrum of cytotoxic base adducts. DNA
      polymerase beta (beta-pol) is required for efficient base excision repair of N
      alkyl adducts, and we make use of the hypersensitivity of beta-pol null mouse
      fibroblasts to investigate such alkylating agents with a view towards
      understanding the DNA lesions responsible for the cellular phenotype. The
      inability of O(6)-benzylguanine to sensitize wild-type or beta-pol null cells to
      S(N)1-type methylating agents indicates that the observed hypersensitivity is not
      due to differential repair of cytotoxic O-alkyl adducts. Using a 3-methyladenine
      specific agent and an inhibitor of such methylation, we find that inefficient
      repair of 3-methyladenine is not the reason for the hypersensitivity of beta-pol
      null cells to methylating agents, and further that 3-methyladenine is not the
      adduct primarily responsible for methyl methanesulfonate (MMS)- and methyl
      nitrosourea-induced cytotoxicity in wild-type cells. Relating the expected
      spectrum of DNA adducts and the relative sensitivity of cells to monofunctional
      alkylating agents, we propose that the hypersensitivity of beta-pol null cells
      reflects accumulation of cytotoxic repair intermediates, such as the 5'
      deoxyribose phosphate group, following removal of 7-alkylguanine from DNA. In
      support of this conclusion, beta-pol null cells are also hypersensitive to the
      thymidine analog 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). This agent is
      incorporated into cellular DNA and elicits cytotoxicity only when removed by
      glycosylase-initiated base excision repair. Consistent with the hypothesis that
      there is a common repair intermediate resulting in cytotoxicity following
      treatment with both types of agents, both MMS and hmdUrd-initiated cell death are
      preceded by a similar rapid concentration-dependent suppression of DNA synthesis
      and a later cell cycle arrest in G(0)/G(1) and G(2)M phases.

PMID- 12509267
TI  - Resistance of p53 knockout cells to doxorubicin is related to reduced formation
      of DNA strand breaks rather than impaired apoptotic signaling.
AB  - The anthracycline doxorubicin (adriamycin) is an important chemotherapeutic agent
      used in the treatment of solid epithelial and mesenchymal tumors as well as
      leukemias. A variety of mechanisms has been proposed to be involved in
      doxorubicin-induced cytotoxicity such as DNA intercalation, oxidative stress, DNA
      strand breakage by inhibition of topoisomerase II, activation of death receptors,
      and altered p53 expression. Concerning doxorubicin resistance and p53 status data
      reported are contradictory. Here, we show that mouse fibroblasts deficient in p53
      (p53(-/-)) are more resistant to doxorubicin than p53 wild-type (p53 wt) cells.
      This is in contrast to other genotoxic agents (UV-light, alkylating drugs) for
      which p53(-/-) fibroblasts proved to be more sensitive. Resistance of p53(-/-)
      cells to doxorubicin is related to reduced induction of apoptosis. This is not
      likely to be due to altered apoptotic signaling since the expression of Bax and
      Bcl-2 was unchanged and the induction of Fas/CD95/APO-1 receptor and caspase-8
      was the same in p53(-/-) and p53 wt cells on treatment with doxorubicin. However,
      we observed a clearly lower level of doxorubicin-induced DNA strand breaks in
      p53(-/-) cells compared to the wt. P170 glycoprotein was equally expressed and
      the accumulation and elimination of the drug occurred with identical kinetics in
      both cell types. p53 deficient cells were cross-resistant to another
      topoisomerase II inhibitor etoposide, which also provoked increased DNA strand
      breakage in p53 wt cells. Based on the data we conclude that the p53 status
      significantly impacts the generation of DNA strand breaks because of drug-induced
      topoisomerase inhibition rather than death receptor signaling. Since human tumors
      are frequently mutated in p53 the findings bear clinical implications.

PMID- 12509268
TI  - Lethality of visible light for Escherichia coli hemH1 mutants influence of
      defects in DNA repair.
AB  - The hemH gene encodes ferrochelatase, the final enzyme of the heme biosynthetic
      pathway. Defects of this enzyme lead to accumulation of protoporphyrin IX and an
      increase in reactive oxygen species, causing susceptibility to blue and white
      light in bacteria and protoporphyria in humans. Here we show that the
      photosensitivity of hemH1 strains is much increased when the bacteria are devoid
      of ability to repair abasic sites. The sensitivity is increased 10- or 50-fold,
      in mutants bearing single xth or triple xth-nth-nfo mutations, respectively, but
      is not changed in mutants bearing nth, fpg, mutY, and mutT that are positive or
      negative for uvrA. This may indicate that in hemH1 mutants abasic sites are
      accumulated to a greater degree than oxidised bases, and/or that protoporphyrin,
      in the presence of abasic sites, increases the photosensitivity of hemH1 cells.
      It was shown in this work that the level of abasic sites (and/or strand breaks)
      in DNA of hemH1 strains increases greatly. Abasic sites and oxidative bases are
      potential mutagenic lesions. Nevertheless, the sensitivity of hemH1 bacteria to
      the lethal effect of visible light is not accompanied by increase in mutations.
      One of the possible explanations is that the genotoxic effect due to damage of
      hemH, shortage of heme and/or accumulating of protoporphyrin IX makes mutagenesis
      impossible.

PMID- 12509269
TI  - DNA mismatch repair and acquired cisplatin resistance in E. coli and human
      ovarian carcinoma cells.
AB  - The contribution of defective DNA mismatch repair (MMR) to acquired resistance to
      cis-diamminedichloroplatinum(II) (cisplatin) has been investigated in two model
      systems: E coli dam mutants and the A2780 ovarian carcinoma cell line.
      Inactivation of MMR-as indicated by the acquisition of an elevated spontaneous
      mutator phenotype-was observed frequently among survivors of cisplatin-treated
      dam mutants. These survivors exhibited a stable resistance to further cisplatin
      treatment. In contrast, none of twelve independent clones of A2780 that had
      survived cisplatin exposure and acquired stable drug resistance were repair
      defective. None exhibited the hallmark methylation tolerant phenotype associated
      with a MMR defect, mRNAs encoding five MMR proteins were easily detectable in all
      twelve variants, and the levels of four key MMR proteins were similar to those in
      the repair proficient parental cells. Further analysis indicated two different
      mechanisms of acquired resistance in A2780. The first was a protective effect
      that reduced the level of DNA platination. The second was observed as a reduced
      sensitivity to cell cycle arrest after cisplatin treatment and a consequent
      reduced apoptosis. The data suggest that although loss of MMR is a significant
      mechanism of acquired drug resistance in dam bacteria, alterations related to DNA
      protection or cell cycle progression after drug damage appear to be more probable
      than abrogation of MMR as resistance modulators in human cells.

PMID- 12509270
TI  - Constitutive and regulated expression of the mouse Dinb (Polkappa) gene encoding
      DNA polymerase kappa.
AB  - A recently discovered group of novel polymerases are characterized by
      significantly reduced fidelity of DNA synthesis in vitro. This feature is
      consistent with the relaxed fidelity required for the replicative bypass of
      various types of base damage that frequently block high fidelity replicative
      polymerases. The present studies demonstrate that the specialized DNA polymerase
      kappa (polkappa) is uniquely and preferentially expressed in the adrenal cortex
      and testis of the mouse, as well as in a variety of other tissues. The adrenal
      cortex is the sole site of detectable expression of the Polkappa gene in mouse
      embryos. This adrenal expression pattern is consistent with a requirement for
      polkappa for the replicative bypass of DNA base damage generated during steroid
      biosynthesis. The expression pattern of polkappa in the testis is specific for
      particular stages of spermatogenesis and is distinct from the expression pattern
      of several other low fidelity DNA polymerases that are also expressed during
      spermatogenesis. The mouse (but not the human) Polkappa gene is primarily
      regulated by the p53 gene and is upregulated in response to exposure to various
      DNA-damaging agents in a p53-dependent manner.

PMID- 12509272
TI  - The beta-lactamase motif in Snm1 is required for repair of DNA double-strand
      breaks caused by interstrand crosslinks in S. cerevisiae.
AB  - The SNM1 gene of Saccharomyces cerevisiae is specific for repair of DNA
      interstrand crosslinks (ICLs). We report that the SNM1 gene functions in steps
      needed for the reformation of chromosomal DNA after double-strand breaks (DSBs)
      made in the process of ICL repair. However, SNM1 function is not needed for
      repair of HO endonuclease-generated DSBs. Therefore, the function of the SNM1
      gene appears to act in the processing of the intermediates of the DSB repair,
      since the rate and extent of DSB appearance after ICL formation is normal in
      mutants lacking SNM1 function. The action of the SNM1 gene does not appear to
      depend on homologous recombination, but it does depend on an intact beta
      lactamase domain conserved with Artemis, a protein required for processing of
      V(D)J recombination intermediates.

PMID- 12509271
TI  - Kinetics and binding of the thymine-DNA mismatch glycosylase, Mig-Mth, with
      mismatch-containing DNA substrates.
AB  - We have examined the removal of thymine residues from T-G mismatches in DNA by
      the thymine-DNA mismatch glycosylase from Methanobacterium thermoautrophicum (Mig
      Mth), within the context of the base excision repair (BER) pathway, to
      investigate why this glycosylase has such low activity in vitro. Using single
      turnover kinetics and steady-state kinetics, we calculated the catalytic and
      product dissociation rate constants for Mig-Mth, and determined that Mig-Mth is
      inhibited by product apyrimidinic (AP) sites in DNA. Electrophoretic mobility
      shift assays (EMSA) provide evidence that the specificity of product binding is
      dependent upon the base opposite the AP site. The binding of Mig-Mth to DNA
      containing the non-cleavable substrate analogue difluorotoluene (F) was also
      analyzed to determine the effect of the opposite base on Mig-Mth binding
      specificity for substrate-like duplex DNA. The results of these experiments
      support the idea that opposite strand interactions play roles in determining
      substrate specificity. Endonuclease IV, which cleaves AP sites in the next step
      of the BER pathway, was used to analyze the effect of product removal on the
      overall rate of thymine hydrolysis by Mig-Mth. Our results support the hypothesis
      that endonuclease IV increases the apparent activity of Mig-Mth significantly
      under steady-state conditions by preventing reassociation of enzyme to product.

PMID- 12509274
TI  - Pivotal role of the beta-clamp in translesion DNA synthesis and mutagenesis in E.
      coli cells.
AB  - The genetic information is continuously subjected to the attack by endogenous and
      exogenous chemical and physical carcinogens that damage the DNA template, thus
      compromising its biochemical functions. Despite the multiple and efficient DNA
      repair systems that have evolved to cope with the large variety of damages, some
      lesions may persist and, as a consequence, interfere with DNA replication. By
      essence, the damaged-DNA replication process (hereafter termed translesion
      synthesis or TLS) is a major source of point mutations and is therefore deeply
      involved in the onset of human diseases such as cancer. Recent identification of
      numerous DNA polymerases involved in TLS has shed new light onto the molecular
      mechanisms of mutagenesis. Here, we show that in vivo, both error-free and
      mutagenic bypass activities of the three DNA polymerases known to be involved in
      TLS in Escherichia coli (PolII, PolIV and PolV) strictly depend upon the
      integrity of small peptidic sequences identified as their beta-clamp binding
      motif. Thus, in addition to its crucial role as the processivity factor of the
      PolIII replicase, the beta-clamp plays a pivotal role during the TLS process.

PMID- 12509275
TI  - OGG1 mRNA expression and incision activity in rats are higher in foetal tissue
      than in adult liver tissue while 8-oxo-2'-deoxyguanosine levels are unchanged.
AB  - This study was set up to investigate the relationships between the formation and
      removal of DNA damage in form of 8-oxodeoxyguanosine (8-oxodG) in neonatal (day
      16 of gestation) as compared to adult rats. The hypothesis addressed was whether
      the rapidly dividing foetal tissue has an enhanced requirement of DNA repair
      providing protection against potentially mutagenic DNA damages such as 8-oxodG.
      The activity of the primary 8-oxodG-repair protein OGG1 was measured by a DNA
      incision assay and the expression of OGG1 mRNA was measured by Real-Time PCR
      normalised to 18S rRNA. The tissue level of 8-oxodG was measured by HPLC-ECD. We
      found a 2-3-fold increased incision activity in the foetal control tissue,
      together with a 3-15-fold increase in mRNA of OGG1 as compared to liver tissue
      from adult rats. The levels of 8-oxodG in the foetal tissue were unaltered as
      compared to the adult groups. To increase the levels of 8-oxodG, the rats
      received an injection (i.p.) of the hepatotoxin 2-nitropropane. The compound
      induced significant levels of 8-oxodG in male rat livers 5h after the injection
      and in the foetuses 24h after the injection, while the female rats showed no
      increase in 8-oxodG. The incision activity was slightly depressed in both male
      and female liver tissue and in the foetal tissue 5h after the injection, but
      significantly increased from 5 to 24h after the injection. However, it did not
      reach levels significantly above the control levels. In conclusion, this study
      confirms that foetal tissue has increased levels of OGG1 mRNA and correspondingly
      an enhanced incision activity on an 8-oxodG substrate in a crude tissue extract.

PMID- 12509276
TI  - Evidence for a direct association of hMRE11 with the human mismatch repair
      protein hMLH1.
AB  - In both mitotic and meiotic processes, cellular surveillance of the integrity of
      genetic information transmission from parental cells to their subsequent
      generations is carried out by a network of proteins primarily involved in cell
      cycle regulation, DNA replication, DNA repair, and chromosome segregation. Within
      this context, the mammalian MRE11 represents an essential multifunctional protein
      that promotes repair of DNA double-strand breaks and plays a role in the
      signaling of DNA damage response. Mutations in human hMRE11 gene could contribute
      to the rare "AT-like" disorder. However, at present time the functional roles of
      hMRE11 in these cellular processes are elusive. In the current study, we provide
      evidence that hMRE11 interacts physically with the mismatch repair protein hMLH1
      through yeast two-hybrid analysis. In addition, we show that recombinant hMRE11
      and hMLH1 proteins interact when these two proteins are coexpressed in bacterial
      cells, and both proteins can be co-immunoprecipitated from human cell extracts.
      Furthermore, hMRE11 and hMLH1 display similar expression patterns when examined
      with a human normal/tumor DNA array. Together, these data suggest that hMRE11 and
      hMLH1 might act in a co-operative fashion during DNA damage detection, signaling,
      and repair.

PMID- 12509277
TI  - Incision of a 1,3-intrastrand d(GpTpG)-cisplatin adduct by nucleotide excision
      repair proteins from yeast.
AB  - The protein machinery responsible for nucleotide excision repair (NER) is highly
      conserved from yeast to man. NER can be reconstituted with purified proteins, and
      the incision sites around a defined DNA lesion have been defined to the
      nucleotide level in a mammalian NER system. Here, we reconstitute NER in yeast
      whole cell extracts, as well as with partially purified yeast NER components. We
      show that NER activity can be isolated partly as a large protein complex, and map
      the sites of nucleotide incision around a cisplatin-induced DNA lesion. Our data
      indicate that yeast NER proteins excise an oligonucleotide of 23-26 bases
      containing the DNA lesion (rather than 26-30 bases as in humans), and that the 3'
      incision occurs around position 17 (rather than at position 9 as in humans).

PMID- 12509278
TI  - Evidence for sequential action of two ATPase active sites in yeast Msh2-Msh6.
AB  - Bacterial MutS homodimers contain two ATPase active sites that have non
      equivalent functions in DNA mismatch repair. The homologous Msh2-Msh6 complex in
      eukaryotes also has intrinsic ATPase activity that is essential for mismatch
      repair. Here, we investigate differences in the two putative ATPase active sites
      by examining the properties of heterodimers containing alanine substituted for an
      invariant glutamic acid in the active site of either Msh2, Msh6 or both. Mutation
      rates in wild type versus Glu-->Ala mutant haploid yeast strains indicate that
      both ATPase active sites are essential for mismatch repair activity in vivo. The
      properties of purified heterodimers suggest that the ATPase active site in Msh6
      binds ATP with higher affinity and hydrolyzes ATP faster and with higher
      efficiency than does the ATPase active site in Msh2. This suggests sequential
      action of the two ATPase active sites, in which ATP binds to Msh6 first to
      trigger downstream events in mismatch repair.

PMID- 12509279
TI  - A novel p53 mutant retained functional activity in lung carcinomas.
AB  - The gene p53 is a critical tumor suppressor that can respond to multiple signals
      of cellular gatekeepers for growth and division. The mdm2 gene is one of the
      downstream target genes for transcriptional activation by the product of p53
      tumor suppressor gene. Transactivation of mdm2 gene is represented by the
      presence of a functional P53 protein. To understand the biological function of
      mutant p53 in tumorigenesis, we constructed a number of p53 mutants by site
      directed mutagenesis (H179Y, L194R, S240R, R249S, A276D, E286Q), followed by
      characterization of each P53 mutant's ability to transactivate mdm2, bax and
      p21waf. The transactivation properties of p53 mutants were compared by co
      transfection with pGL-3-mdm2, pGL-3-bax and pGL-3-p21waf into the P53 null cell
      line H1299 derived from a non-small cell lung carcinoma. Among them mt p53 S240R
      and E286Q were shown to have enhanced transactivating activity of pGL3-mdm2, at
      about 43.2 and 28.2% of the wt p53 vector, respectively, while the remaining four
      had nearly the same level of activity as the negative control did. Furthermore,
      data indicated that mt p53 S240R had as high an ability to suppress the growth of
      the p53 null cell line H1299 as wild type p53. Therefore, mutant p53 alone is an
      insufficient indicator of poor prognosis. Instead, functional p53 may affect lung
      cancer prognosis.

PMID- 12509280
TI  - Examining the potential role of DNA polymerases eta and zeta in triplet repeat
      instability in yeast.
AB  - Triplet repeats undergo frequent mutations in human families afflicted with
      certain neurodegenerative diseases and also in model organisms. Although the
      molecular mechanisms of triplet repeat instability are still being identified, it
      is likely that aberrant DNA synthesis plays an important role. Many DNA
      polymerases stall at triplet repeat sequences, probably due to the adoption of
      unusual DNA secondary structures. One possible mechanism to explain triplet
      repeat contractions is that a triplet repeat hairpin on the template strand
      inhibits replicative polymerases and that one or more bypass polymerases are
      recruited for synthesis past the hairpin. If the translesion synthesis is
      mutagenic, contractions can be generated. To address this possibility,
      Saccharomyces cerevisiae strains lacking either pol zeta (rev7), pol eta (rad30),
      or both were tested for trinucleotide repeat (TNR) contractions using three
      separate, sensitive genetic assays. If these bypass polymerases are important for
      mutagenesis, then the mutants should show a reduction in the contraction rate.
      Two genetic tests for triplet repeat contractions showed no significant change
      for the mutants compared to wild type. A third assay showed a five-fold reduction
      in contraction rates due to pol eta ablation. Despite this modest decrease, the
      overall contraction rate was still high, indicating that many deletions still
      occur in the absence of both polymerases. Expansion rates were also unaffected in
      the mutant strains. These results indicate that, in yeast, pol eta and pol zeta
      most likely have little role in triplet repeat mutagenesis.

PMID- 12509281
TI  - The Greek Goddess, Artemis, reveals the secrets of her cleavage.
AB  - A recent paper in Cell by Ma et al. [Cell 8 (2002) 781] showed that the protein
      Artemis cleaves a hairpin intermediate during V(D)J recombination. Peter O'Neill
      and Penny Jeggo discuss this finding in the light of evidence that Artemis also
      functions to repair radiation damage [Cell 105 (2001) 177]. The findings suggest
      that Artemis may function in double strand break repair by "tidying up" double
      strand ends with associated base damage. The development of genetic diversity
      during immune development, therefore, seems to exploit damage response mechanisms
      that function to maintain genetic stability in other cell lineages.

PMID- 12509283
TI  - Arabidopsis thaliana, a versatile model system for study of eukaryotic genome
      maintenance functions.
AB  - The genome of the model plant Arabidopsis thaliana encodes many orthologs of
      human genome-maintenance proteins, and in several important cases plant DNA
      repair and mutation-antagonism functions resemble their mammalian counterparts
      more closely than do those of established microbial models. These orthologs, in
      conjunction with the powerful tools now available for work with Arabidopsis and
      the practical advantages of its small size and rapid life cycle, now make it an
      attractive model system for study of eukaryotic DNA repair and mutagenesis.
      Already, null mutations that inactivate proteins involved in repair of DNA double
      strand breaks or in DNA translesion synthesis and are lethal in mice have proved
      to be tolerated by plants. This review compares in some detail the genome
      maintenance activities encoded by plants, mammals and microbes, and describes
      important Arabidopsis tools and life cycle characteristics. It concludes with
      selected examples that illustrate Arabidopsis advantages and/or reveal new
      insights into genome-maintenance functions of general interest.

PMID- 12509284
TI  - Xeroderma pigmentosum complementation group E and UV-damaged DNA-binding protein.
AB  - UV-damaged DNA-binding protein (UV-DDB) is composed of two subunits, DDB1 (p127)
      and DDB2 (p48). Mutations in the DDB2 gene inactivate UV-DDB in individuals from
      complementation group E of xeroderma pigmentosum (XP-E), an autosomal recessive
      disease characterized by sun sensitivity, severe risk for skin cancer and
      defective nucleotide excision repair. UV-DDB is also deficient in many rodent
      tissues, exposing a shortcoming in rodent models for cancer. In vitro, UV-DDB
      binds to cyclobutane pyrimidine dimers (CPDs), 6-4 photoproducts and other DNA
      lesions, stimulating the excision of CPDs, and to a lesser extent, of 6-4
      photoproducts. In vivo, UV-DDB plays an important role in the p53-dependent
      response of mammalian cells to DNA damage. When cells are exposed to UV, the
      resulting accumulation of p53 activates DDB2 transcription, which leads to
      increased levels of UV-DDB. Binding of UV-DDB to CPDs targets these lesions for
      global genomic repair, suppressing mutations without affecting UV survival.
      Apparently, cells are able to survive with unrepaired CPDs because of the
      activity of bypass DNA polymerases. Finally, there is evidence that UV-DDB may
      have roles in the cell that are distinct from DNA repair.

PMID- 12509285
TI  - Effects of hexavalent chromium on the survival and cell cycle distribution of DNA
      repair-deficient S. cerevisiae.
AB  - A broad spectrum of genetic damage results from exposure to hexavalent chromium.
      These lesions can result in DNA and RNA polymerase arrest, chromosomal
      aberrations, point mutations and deletions. Because of the complexity of Cr
      genotoxicity, the repair of Cr(VI)-induced DNA damage is poorly understood.
      Therefore, our aim was to investigate the sensitivities of DNA repair-deficient
      Saccharomyces cerevisiae strains to Cr(VI)-induced growth inhibition and
      lethality. Wild-type, translesion synthesis (rev3) and excision repair (apn1,
      ntg1, ntg2, rad1) mutants exhibited similar survival following Cr(VI) treatment
      (0-50mM) and underwent at least one population doubling within 2-4h post
      treatment. The simultaneous loss of several excision repair genes (apn1 rad1 ntg1
      ntg2) led to slower growth after Cr(VI) exposure (10mM) manifested as an initial
      delay in S phase progression. Higher concentrations of Cr(VI) (25mM) resulted in
      a prolonged transit through S phase in every strain tested. A G(2)/M arrest was
      evident within 1-2h after Cr(VI) treatment (10mM) in all strains and cells
      subsequently divided after this transient delay. In contrast to all other
      strains, only recombination-deficient (rad52, rad52 rev3) yeast were markedly
      hypersensitive towards Cr(VI) lethality. RAD52 mutant strains (rad52, rad52 rev3)
      also exhibited a significant delay (>6h) in the resumption of replication after
      Cr(VI) exposure which was related to the immediate and apparently terminal arrest
      of these yeast in G(2)/M after Cr(VI) treatment. These results, taken together
      with the recombinogenic effects of Cr(VI) in yeast containing a functional RAD52
      gene, suggest that RAD52-mediated recombination is critical for the normal
      processing of lethal Cr-induced genetic lesions and exit from G(2) arrest.
      Furthermore, only the combined inactivation of multiple excision repair genes
      affects cell growth after Cr(VI) treatment.

PMID- 12509286
TI  - Ultraviolet-sensitive syndrome cells are defective in transcription-coupled
      repair of cyclobutane pyrimidine dimers.
AB  - Patients with ultraviolet-sensitive syndrome (UV(S)S) are sensitive to sunlight,
      but present neither developmental nor neurological deficiencies. Complementation
      studies with hereditary DNA repair syndromes show that UV(S)S is distinct from
      all known xeroderma pigmentosum (XP) and Cockayne syndrome (CS) groups. UV(S)S
      cells exhibit some characteristics typical of CS, including normal global genomic
      (GGR) repair of UV-photoproducts, poor clonal survival and defective recovery of
      RNA synthesis after UV exposure. Those observations have led us to suggest that
      UV(S)S cells, like those from CS, are defective in transcription-coupled repair
      (TCR) of cyclobutane pyrimidine dimers (CPD). We have now examined the repair of
      CPD in the transcribed and non-transcribed strands of the active dihydrofolate
      reductase (DHFR) and p53 genes, and of the silent alpha-fetoprotein (AFP) and mid
      size neurofilament (NF-M) genes in normal human cells and in cells belonging to
      UV(S)S and CS complementation group B. Our results provide compelling evidence
      that the UV(S)S gene is essential for TCR of CPD and probably other bulky DNA
      lesions. As a possible distinction between UV(S)S and CS patients, we postulate
      that the UV(S)S gene may not be required for TCR of oxidative lesions. We have
      also found that repair of CPD in either DNA strand of the genomic fragments
      examined, occurs at a slower rate in TCR-deficient cells than in the non
      transcribed strands in normal cells; we suggest that in the absence of TCR,
      global repair complexes have hindered access to lesions in genomic regions that
      extend beyond individual transcription units.

PMID- 12509287
TI  - The S. cerevisiae Mag1 3-methyladenine DNA glycosylase modulates susceptibility
      to homologous recombination.
AB  - DNA glycosylases, such as the Mag1 3-methyladenine (3MeA) DNA glycosylase,
      initiate the base excision repair (BER) pathway by removing damaged bases to
      create abasic apurinic/apyrimidinic (AP) sites that are subsequently repaired by
      downstream BER enzymes. Although unrepaired base damage may be mutagenic or
      recombinogenic, BER intermediates (e.g. AP sites and strand breaks) may also be
      problematic. To investigate the molecular basis for methylation-induced
      homologous recombination events in Saccharomyces cerevisiae, spontaneous and
      methylation-induced recombination were studied in strains with varied MAG1
      expression levels. We show that cells lacking Mag1 have increased susceptibility
      to methylation-induced recombination, and that disruption of nucleotide excision
      repair (NER; rad4) in mag1 cells increases cellular susceptibility to these
      events. Furthermore, expression of Escherichia coli Tag 3MeA DNA glycosylase
      suppresses recombination events, providing strong evidence that unrepaired 3MeA
      lesions induce recombination. Disruption of REV3 (required for polymerase zeta
      (Pol zeta)) in mag1 rad4 cells causes increased susceptibility to methylation
      induced toxicity and recombination, suggesting that Pol zeta can replicate past
      3MeAs. However, at subtoxic levels of methylation damage, disruption of REV3
      suppresses methylation-induced recombination, indicating that the effects of Pol
      zeta on recombination are highly dose-dependent. We also show that overproduction
      of Mag1 can increase the levels of spontaneous recombination, presumably due to
      increased levels of BER intermediates. However, additional APN1 endonuclease
      expression or disruption of REV3 does not affect MAG1-induced recombination,
      suggesting that downstream BER intermediates (e.g. single strand breaks) are
      responsible for MAG1-induced recombination, rather than uncleaved AP sites. Thus,
      too little Mag1 sensitizes cells to methylation-induced recombination, while too
      much Mag1 can put cells at risk of recombination induced by single strand breaks
      formed during BER.

PMID- 12509288
TI  - Inactivation of mammalian 8-oxoguanine-DNA glycosylase by cadmium(II):
      implications for cadmium genotoxicity.
AB  - Cadmium(II) is a toxic, mutagenic and carcinogenic metal (IARC Class 1 human
      carcinogen). It causes damage to eukaryotic cells both in acute and chronic modes
      of exposure via multiple biochemical mechanisms. In particular, Cd diminishes the
      capacity of cells to repair oxidative DNA damage. Oxidative DNA lesions are
      important precursors to mutations and ultimately may lead to neoplastic
      transformation of human cells. We investigated interactions of Cd with murine
      Ogg1 (mOgg1), an enzyme that removes 8-oxoguanine (8-oxoG), an abundant oxidative
      lesion, from DNA. Cd(2+) and Zn(2+), but not other divalent cations tested,
      suppressed mOgg1-catalyzed reactions. The apparent inhibition by Cd consisted of
      at least two independent processes: irreversible, DNA-independent first-order
      inactivation of mOgg1 and DNA-dependent inhibition. Irreversibly inactivated
      mOgg1 has nearly normal affinity for damaged DNA and a normal catalytic rate
      constant but is defective in formation of the covalent reaction intermediate.
      When both modes of inhibition are in effect, the catalytic rate constant is
      dramatically lowered, while affinity to damaged DNA is decreased moderately.
      Potential sites for Cd binding in mOgg1 and mOgg1-DNA complex are identified.
      Inactivation of Ogg1 may play a role in the mutagenic and carcinogenic action of
      Cd.

PMID- 12509289
TI  - Characterization of the slow-growth phenotype of S. cerevisiae Whip/Mgs1 Sgs1
      double deletion mutants.
AB  - RecQ DNA helicases from many organisms have been indicated to function in the
      maintenance of genomic stability. In human cells, mutation in the WRN helicase, a
      RecQ-like DNA helicase, results in the Werner syndrome (WS), a genetic disorder
      characterized by genomic instability and premature ageing. Similarly, mutation in
      SGS1, the RECQ homologue in budding yeast, results in genomic instability and
      accelerated ageing. We previously demonstrated that mouse WRN interacts
      physically with a novel, highly conserved protein that we named WHIP, and that in
      budding yeast cells, simultaneous deletion of WHIP/MGS1 and SGS1 results in slow
      growth and shortened life span. Here we show by using genetic analysis in
      Saccharomyces cerevisiae that mgs1Delta sgs1Delta cells have increased rates of
      terminal G2/M arrest, and show elevated rates of spontaneous sister chromatid
      recombination (SCR) and rDNA array recombination. Finally, we report that
      complementation of the synthetic relationship between SGS1 and WHIP/MGS1 requires
      both the helicase and Top3-binding activities of Sgs1, as well as the ATPase
      activity of Mgs1. Our results suggest that Whip/Mgs1 is implicated in DNA
      metabolism, and is required for normal growth and cell cycle progression in the
      absence of Sgs1.

PMID- 12509292
TI  - A DNA damage checkpoint in Escherichia coli.
AB  - An early attempt to find out if the DNA double helix is actively unwound before
      being replicated was not conclusive, but it did disclose the existence of a
      unique moment in the life cycle of Escherichia coli when the cell registers
      whether or not its DNA is intact. If not, the cell embarks on rapid breakdown of
      its DNA, like "apoptosis" in eukaryotic cells.

PMID- 12509290
TI  - Base excision repair and nucleotide excision repair contribute to the removal of
      N-methylpurines from active genes.
AB  - Many different cellular pathways have evolved to protect the genome from the
      deleterious effects of DNA damage that result from exposure to chemical and
      physical agents. Among these is a process called transcription-coupled repair
      (TCR) that catalyzes the removal of DNA lesions from the transcribed strand of
      expressed genes, often resulting in a preferential bias of damage clearance from
      this strand relative to its non-transcribed counterpart. Lesions subject to this
      type of repair include cyclobutane pyrimidine dimers that are normally repaired
      by nucleotide excision repair (NER) and thymine glycols (TGs) that are removed
      primarily by base excision repair (BER). While the mechanism underlying TCR is
      not completely clear, it is known that its facilitation requires proteins used by
      other repair pathways like NER. It is also believed that the signal for TCR is
      the stalled RNA polymerase that results when DNA damage prevents its
      translocation during transcription elongation. While there is a clear role for
      some NER proteins in TCR, the involvement of BER proteins is less clear. To
      explore this further, we studied the removal of 7-methylguanine (7MeG) and 3
      methyladenine (3MeA) from the dihydrofolate reductase (dhfr) gene of murine cell
      lines that vary in their repair phenotypes. 7MeG and 3MeA constitute the two
      principal N-methylpurines formed in DNA following exposure to methylating agents.
      In mammalian cells, alkyladenine DNA alkyladenine glycosylase (Aag) is the major
      enzyme required for the repair of these lesions via BER, and their removal from
      the total genome is quite rapid. There is no observable TCR of these lesions in
      specific genes in DNA repair proficient cells; however, it is possible that the
      rapid repair of these adducts by BER masks any TCR. The repair of 3MeA and 7MeG
      was examined in cells lacking Aag, NER, or both Aag and NER to determine if rapid
      overall repair masks TCR. The results show that both 3MeA and 7MeG are removed
      without strand bias from the dhfr gene of BER deficient (Aag deficient) and NER
      deficient murine cell lines. Furthermore, repair of 3MeA in this region is highly
      dependent on Aag, but repair of 7MeG is equally efficient in the repair
      proficient, BER deficient, and NER deficient cell lines. Strikingly, in the
      absence of both BER and NER, neither 7MeG nor 3MeA is repaired. These results
      demonstrate that NER, but not TCR, contributes to the repair of 7MeG, and to a
      lesser extent 3MeA.

PMID- 12509293
TI  - DNA Repair-responses to DNA damage and other aspects of genomic stability. A new
      journal format.

PMID- 12509294
TI  - ATM deficiency and oxidative stress: a new dimension of defective response to DNA
      damage.
AB  - ATM is one of the sentries at the gate of genome stability. This multifunctional
      protein kinase orchestrates the intricate array of cellular responses to DNA
      double-strand breaks. Absence or inactivation of ATM leads to the pleiotropic
      genetic disorder ataxia-telangiectasia (A-T), whose hallmarks are neuronal
      degeneration, immunodeficiency, genomic instability, premature aging and cancer
      predisposition. Several features of the complex clinical and cellular phenotype
      of A-T are reminiscent of other syndromes involving neurodegeneration, premature
      aging or genomic instability. A common denominator of many of these conditions is
      the perturbation of the cellular balance of reactive oxygen species, which leads
      to constant oxidative stress. Of these disorders, ATM deficiency is one of the
      most extensively studied with regard to the genome instability-oxidative stress
      connection. This connection may provide new insights into the phenotypes
      associated with genetic deficiencies of DNA damage responses, and point to new
      strategies to alleviate some of their clinical symptoms.

PMID- 12509295
TI  - Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA
      repair and telomere length maintenance.
AB  - In Saccharomyces cerevisiae, Mre11p, Rad50p, and Xrs2p function as a multiprotein
      complex that has a central role in several DNA repair mechanisms. Though Mre11p
      has both single-stranded and double-stranded 3'-5' exonuclease activity in vitro,
      null mutants of MRE11, RAD50, and XRS2 exhibit reduced 5'-3' resection of HO
      induced double-strand breaks (DSBs) in vivo. In this study, we analyzed four
      mre11 mutants harboring changes in the N-terminus of Mre11p where the four
      phosphoesterase motifs specify the in vitro nuclease activities of Mre11p and its
      homologues. We find that the 5'-3' resection defects in vivo do not correlate
      with several mitotic phenotypes: non-homologous end-joining (NHEJ), telomere
      length maintenance, and adaptation to the DNA damage-inducible G2/M checkpoint.
      Overexpression of the 5'-3' exonuclease Exo1p in a mre11Delta strain partially
      increased 5'-3' resection and partially suppressed both methyl methanesulfonate
      (MMS) hypersensitivity and adaptation phenotypes, but did not affect telomere
      length or NHEJ. Surprisingly, the co-expression of two alleles, mre11-58S and
      mre11-N113S, each of which confers MMS hypersensitivity and short telomeres, can
      fully complement the MMS sensitivity and shortened telomere length of mre11Delta
      cells. We propose that at least two separate activities associated with the N
      terminus of Mre11p are required for its mitotic function.

PMID- 12509296
TI  - Polymerase eta and p53 jointly regulate cell survival, apoptosis and Mre11
      recombination during S phase checkpoint arrest after UV irradiation.
AB  - Xeroderma pigmentosum variant (XPV) cells lack the damage-specific polymerase eta
      and undergo a protracted arrest at the S phase checkpoint(s) following UV damage.
      The S phase checkpoints encompass several qualitatively different processes, and
      stimulate downstream events that are dependent on the functional state of p53.
      Primary fibroblasts with wild-type p53 arrest in S, and require a functional
      polymerase eta (pol eta) to carry out bypass replication, but do not recruit
      recombination factors for recovery. XPV cells with non-functional p53, as a
      result of transformation by SV40 or HPV16 (E6/E7), recruit the hMre11/hRad50/Nbs1
      complex to arrested replication forks, coincident with PCNA, whereas normal
      transformed cells preferentially use the pol eta bypass replication pathway. The
      formation of hMre11 foci implies that arrested replication forks rapidly undergo
      a collapse involving double strand breakage and rejoining. Apoptosis occurs after
      UV only in cells transformed by SV40, and not in normal or XPV fibroblasts or
      HPV16 (E6/E7) transformed cells. Conversely, ultimate cell survival in XPV cells
      was much less in HPV16 (E6/E7) transformed cells than in SV40 transformed cells,
      indicating that apoptosis was not a reliable predictor of cell survival.
      Inhibition of p53 transactivation by pifithrin-alpha or inhibition of protein
      synthesis by cycloheximide did not induce hMre11 foci or apoptosis in UV damaged
      fibroblasts. Inhibition of kinase activity with wortmannin did not increase
      killing by UV, unlike the large increase seen with caffeine. Since HPV16 (E6/E7)
      transformed XPV cells were highly UV sensitive and not further sensitized by
      caffeine, it appears likely that caffeine sensitization proceeds through a p53
      pathway. The S phase checkpoints are therefore, a complex set of different
      checkpoints that are coordinated by p53 with the capacity to differentially
      modulate cell survival, apoptosis, bypass replication and hMre11 recombination.

PMID- 12509297
TI  - DNA repair in terminally differentiated cells.
AB  - Terminally differentiated cells do not replicate their genomic DNA, and could
      therefore dispense with the task of removing DNA damage from the non-essential
      bulk of their genome, as long as they are able to maintain the integrity of the
      genes that must be expressed. There is increasing experimental evidence that this
      is indeed the case, at least for some repair pathways such as nucleotide excision
      repair (NER). In this review, we examine a number of terminally differentiated
      cell systems in which it has been demonstrated that DNA repair is attenuated at
      the global genome level, but maintained in expressed genes. How these cells
      manage to repair transcribed genes is not yet fully elucidated, but there are
      indications that the transcription-coupled repair (TCR) pathway could maintain
      integrity of the transcribed strand (TS) in the active genes. We have observed in
      neurons that the non-transcribed strand (NTS) of active genes is also well
      repaired, a phenomenon that we have named differentiation-associated repair
      (DAR). It is conceivable that DAR is necessary to maintain the integrity of the
      template strand that is needed by TCR to complete the repair of lesions in the TS
      of essential expressed genes with high fidelity.

PMID- 12509298
TI  - A model for the structure of the Escherichia coli SOS-regulated UmuD2 protein.
AB  - The ubiquitous Y-family of DNA polymerases, exemplified by the Escherichia coli
      UmuC protein (the catalytic subunit of DNA Pol V), possess the remarkable ability
      to replicate imperfect DNA templates that cannot be replicated by other types of
      DNA polymerases. Since this ability comes at the cost of a reduced fidelity, it
      is important that organisms manage these unique polymerases to coordinate their
      actions with those of the replication machinery. In E. coli, it is becoming
      evident that a sophisticated series of protein-protein interactions involving the
      two forms of the umuD gene product, UmuD and UmuD' and components of the
      replicative DNA polymerase serve to manage the actions of the umuC-encoded DNA
      polymerase. The purpose of this study was to better understand how structural
      differences between UmuD2 and UmuD2' help to determine which biological role the
      umuDC gene products will play; the UmuD2C complex functions as a DNA damage
      checkpoint effector, while the UmuD2'C complex participates in translesion DNA
      synthesis, which serves as the mechanistic basis for most chemical and UV light
      mutagenesis. Based on the results of a combination of disulfide cross-linking
      experiments, measurements of solvent accessibility and electron paramagnetic spin
      resonance (EPR) studies, we have developed a refined model for the structure of
      the UmuD2 homodimer. In the model that we are proposing, the N-terminal arms of
      UmuD (residues 1-39) form an extended interface in the UmuD2 homodimer by folding
      down over the globular domains of their intradimer partners. As a result,
      significant portions of the surface of each globular domain are buried in the
      UmuD2 homodimer. Based on the structure of the UmuD2' homodimer, both in the
      crystal and in solution, these same surfaces are exposed. Implications of these
      structural differences between the UmuD2 and the UmuD2' homodimers with respect
      to their roles in managing the actions of the umuC-encoded DNA polymerase are
      discussed.

PMID- 12509300
TI  - Ramifications of personality disorder in clinical practice.

PMID- 12509299
TI  - A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum
      group C protein complex.
AB  - The XPC-HR23B complex is involved in DNA damage recognition and the initiation of
      global genomic nucleotide excision repair (GG-NER). Our previous studies
      demonstrate that XPC-HR23B recognizes and binds DNA containing a helix
      distortion, regardless of the presence or absence of damaged bases. Here, we
      describe an extended analysis of the DNA binding specificity of XPC-HR23B using
      various defined DNA substrates. Although XPC-HR23B showed significantly higher
      affinity for single-stranded DNA than double-stranded DNA, specific secondary
      structures of DNA, involving a single- and double-strand junction, were strongly
      preferred by the complex. This indicates that the presence of bases, which cannot
      form normal Watson-Crick base pairs in double-stranded DNA, is a critical factor
      in determining the specificity of XPC-HR23B binding. A DNase I footprint
      analysis, using a looped DNA substrate, revealed that a single XPC-HR23B complex
      protected a distorted site in an asymmetrical manner, consistent with the
      preferred secondary structure. The specific binding of XPC-HR23B is undoubtedly
      an important molecular process, based on which NER machinery detects a wide
      variety of lesions that vary in terms of chemical structure during DNA repair.

PMID- 12509301
TI  - Epidemiology, public health and the problem of personality disorder.
AB  - BACKGROUND: The public health problem-solving paradigm is a comprehensive method
      not previously applied to preventive interventions for personality disorder.
      AIMS: To present an overview for clinical psychiatrists. METHOD: Review of
      epidemiological research into DSM-IV Axis Il disorders and application to the
      paradigm. RESULTS: Personality disorder affects a substantial proportion of the
      population. Burdens on health care, social and criminal justice agencies have yet
      to be accurately quantified. Debates continue over case definition, but there is
      increasing information on prevalence using 'broad' definitions and aetiology. A
      conceptual framework, based on development, suggests preventive interventions
      should be targeted in childhood. The public health approach also requires
      monitoring of risk factors operating at the population level. CONCLUSIONS:
      Services in England and Wales for persons with personality disorder are currently
      inadequate. The problem-solving paradigm suggests new preventive interventions.
      Psychiatrists should renegotiate their relationship with policy-makers and
      reconsider their preventive role.

PMID- 12509302
TI  - Early identification of individuals at risk for antisocial personality disorder.
AB  - BACKGROUND: Antisocial personality disorder is usually preceded by serious and
      persistent conduct problems starting in early childhood, and so there is little
      difficulty in identifying an at-risk group. AIMS: To address six key areas
      concerning the relationship between early conduct problems and antisocial
      personality disorder. METHOD: Review of recent research into early identification
      of and intervention in child conduct problems, following up to possible adult
      antisocial behaviour. RESULTS: Conduct problems are predictive of antisocial
      personality disorder independently of the associated adverse family and social
      factors. Prediction could be aided through identification of subtypes of conduct
      problems. There is limited evidence on which children have problems that are
      likely to persist and which will improve; children who desist from early conduct
      problems and those with onset in adolescence are also vulnerable as adults.
      CONCLUSIONS: The predictive power of the childhood precursors of antisocial
      personality disorder provides ample justification for early intervention. Greater
      understanding of subgroups within the broad category of antisocial children and
      adults should assist with devising and targeting interventions.

PMID- 12509303
TI  - Treatment models for those with severe mental illness and comorbid personality
      disorder.
AB  - BACKGROUND: Dual diagnosis of personality disorder and severe mental illness is
      an important clinical association that has been under-researched with regard to
      clinical management. AIMS: To compare the outcomes of different treatment models.
      METHOD: The outcome of patients with this combined diagnosis was compared in a
      systematic review of three randomised controlled trials in which different forms
      of community outreach treatment or intensive case management were compared with
      standard care. RESULTS: The results from the three studies showed that the
      outcome of comorbid diagnoses was worse than that of single diagnoses. Although
      assertive approaches reduced in-patient care, they sometimes did so at the
      expense of increasing social dysfunction and behavioural disturbance.
      CONCLUSIONS: For those with comorbid severe mental illness and personality
      disorder, the policy of assertive outreach and care in community settings may be
      inappropriate for both public and patients unless modified to take account of the
      special needs of this group.

PMID- 12509304
TI  - Theories of general personality and mental disorder.
AB  - BACKGROUND: A major shortcoming of current research into personality is its
      failure to explore the relationship between theories of general personality and
      mental disorder. AIMS: To provide preliminary data to address this deficit.
      METHOD: In the first of two studies, we examined the relationship between the
      Neuroticism, Extraversion and Other - Five-Factor Inventory (NEO-FFI) and DSM
      personality disorders in a consecutive series of mentally disordered offenders.
      In the second, we sought to separate the personality dimension neuroticism from
      symptoms of depressive disorder in a sample of subjects with current depression.
      RESULTS: Factors from the NEO-FFI were associated with different personality
      disorders in a predictable manner (first study). It was possible to identify a
      component of neuroticism (i.e. 'worry') that could be separated from depressive
      symptoms (second study). CONCLUSIONS: Theories of general personality theory can
      enlighten and refine descriptions of abnormal mental states by informing both
      their aetiology and their prognosis.

PMID- 12509305
TI  - Therapeutic community treatment of personality disorder: service use and
      mortality over 3 years' follow-up.
AB  - BACKGROUND: A number of studies have demonstrated reductions in the utilisation
      of psychiatric services, especially acute in-patient admissions, following
      therapeutic community treatment of personality disorder. These studies have,
      however, been of limited duration (1 year) and follow-up has not always been
      complete. AIMS: To identify hospital admissions before and after therapeutic
      community treatment of personality disorder. METHOD: A naturalistic clinical
      cohort of patients admitted between January 1993 and December 1995 was followed
      up for 3 years. All subjects were traced to their current consultant
      psychiatrist, general practitioner or death. RESULTS: All patients were traced at
      3-year follow-up. The significant reduction in in-patient admissions seen in the
      first year was maintained over 3 years. Those with the poorest outcomes, suicide,
      accidental death or prolonged admission were all in the quartile with the
      shortest admissions (under 42 days) to the therapeutic community. CONCLUSIONS:
      Previously reported reductions in psychiatric admissions following therapeutic
      community treatment of personality disorder are maintained over 3 years.

PMID- 12509306
TI  - Diagnosis of personality disorders in learning disability.
AB  - BACKGROUND: Though contentious, the diagnosis of personality disorders in persons
      with learning disability is clinically relevant because it affects many aspects
      of management. AIMS: To examine published literature on the diagnosis of
      personality disorders in learning disability. METHOD: Selective review with
      computerised (Medline, Embase and PsychInfo) and manual literature searches.
      RESULTS: The variation in the co-occurrence of personality disorder in learning
      disability, with prevalence ranging from less than 1% to 91% in a community
      setting and 22% to 92% in hospital settings, is very great and too large to be
      explained by real differences. CONCLUSIONS: The diagnosis of personality
      disorders in learning disability is complex and difficult, particularly in those
      with severe disability. Developing consensus diagnostic criteria, specific for
      various developmental levels, is one way forward. Such criteria may need to
      include objective proxy measures such as behavioural observations and informant
      accounts.

PMID- 12509307
TI  - Use of the Global Assessment of Function scale in learning disability.
AB  - BACKGROUND: The Global Assessment of Function (GAF) scale is widely used in adult
      psychiatric practice and research but it has not often been used in learning
      disability, which is inherently more complex. AIMS: To evaluate the reliability
      of GAF in the assessment of learning disability. METHOD: GAF reliability was
      tested by simultaneous multiple rating of unselected case vignettes (n=19-25)
      from health professionals of different disciplines, under controlled conditions.
      Analysis of reliability was made with the intraclass correlation coefficient
      (R(1)) with separate assessments to determine rater bias and individual
      performance of raters. RESULTS: The results of three data-sets showed generally
      poor overall levels of agreement, with R(1) levels of 0.35 and 0.28 and somewhat
      better levels for current GAF scores (R(1)=0.49). However, a subset of raters was
      identified that achieved much higher levels (R(1)=0.54 to 0.74). CONCLUSIONS: The
      GAF, in its current format, is not reliable enough to be used in the routine
      assessment of learning disability. A subgroup of raters, however, have ratings
      that are, by current biostatistical criteria, sufficiently reliable.

PMID- 12509308
TI  - Detection and management of psychiatric disorders in primary care.

PMID- 12509309
TI  - A new report on violence - a welcome and a warning.

PMID- 12509310
TI  - Neurobiological basis of psychopathy.

PMID- 12509311
TI  - Electroconvulsive therapy - state of the art.

PMID- 12509312
TI  - Should there be separate psychiatric services for ethnic minority groups?

PMID- 12509313
TI  - Clinical effects of sexual abuse on people with learning disability: critical
      literature review.
AB  - BACKGROUND: There are few publications concerning the psychological reactions of
      people with learning disabilities to sexual abuse. Most significantly, there are
      no controlled studies and few which demonstrate a systematic approach to
      documenting the sequelae of trauma. AIMS: To critically review the published
      research in this field. METHOD: A literature search in peer-reviewed psychiatry,
      psychology, nursing and social care journals for the years 1974 to 2001 was
      conducted and 25 studies were reviewed. RESULTS: Several studies suggest that,
      following sexual abuse, people with learning disabilities may experience a range
      of psychopathology similar to that experienced by adults and children in the
      general population. However, because of methodological limitations, these results
      are not conclusive. CONCLUSIONS: Whether people with learning disabilities
      experience reactions to sexual abuse similar to the general population has yet to
      be explored by systematic research.

PMID- 12509314
TI  - Impact of the ICD-10 Primary Health Care (PHC) diagnostic and management
      guidelines for mental disorders on detection and outcome in primary care. Cluster
      randomised controlled trial.
AB  - BACKGROUND: The World Health Organization (WHO) ICD-10 Primary Health Care (PHC)
      Guidelines for Diagnosis and Management of Mental Disorders (1996) have not been
      evaluated in a pragmatic randomised controlled trial (RCT). AIMS: To evaluate the
      effect of local adaptation and dissemination of the guidelines. METHOD:
      Pragmatic, pair-matched, cluster RCT involving 30 practices. RESULTS: Guideline
      practices were less sensitive but more specific in identifying morbidity, but
      these differences were not significant. Guideline patients did not differ from
      usual-care patients on 12-item General Health Questionnaire scores at 3-month
      follow-up or in the proportion who were still cases. There were no significant
      differences in secondary outcomes. CONCLUSIONS: Attempts to influence clinician
      behaviour through a process of adaptation and extension of guidelines are
      unlikely to change detection rates or outcomes.

PMID- 12509315
TI  - Death rate from ischaemic heart disease in Western Australian psychiatric
      patients 1980-1998.
AB  - BACKGROUND: People with mental illness suffer excess mortality due to physical
      illnesses. AIMS: To investigate the association between mental illness and
      ischaemic heart disease (IHD) hospital admissions, revascularisation procedures
      and deaths. METHOD: A population-based record-linkage study of 210 129 users of
      mental health services in Western Australia during 1980-1998. IHD mortality
      rates, hospital admission rates and rates of revascularisation procedures were
      compared with those of the general population. RESULTS: IHD (not suicide) was the
      major cause of excess mortality in psychiatric patients. In contrast to the rate
      in the general population, the IHS mortality rate in psychiatric patients did not
      diminish over time. There was little difference in hospital admission rates for
      IHD between psychiatric patients and the general community, but much lower rates
      of revascularisation procedures with psychiatric patients, particularly in people
      with psychoses. CONCLUSIONS: People with mental illness do not receive an
      equitable level of intervention for IHD. More attention to their general medical
      care is needed.

PMID- 12509316
TI  - Developmental precursors of child- and adolescent-onset schizophrenia and
      affective psychoses: diagnostic specificity and continuity with symptom
      dimensions.
AB  - BACKGROUND: An increased rate of premorbid impairment has been reported in both
      child- and adolescent-onset schizophrenic and affective psychoses. AIMS: To
      examine the evidence for a specific association between premorbid impairment and
      child- and adolescent-onset schizophrenia, and whether specific continuities
      exist between premorbid impairments and psychotic symptom dimensions. METHOD:
      Retrospective case note study of 110 first-episode child- and adolescent-onset
      psychoses (age 10-17 years). DSM-III-R diagnoses derived from the OPCRIT
      algorithm showed 61 with schizophrenia (mean age 14.1 years) and 49 with other
      non-schizophrenic psychoses (mean age 14.7 years). RESULTS: Premorbid social
      impairment was more common in early-onset schizophrenia than in other early-onset
      psychoses (OR 1.9, P=0.03). Overall, impaired premorbid development, enuresis and
      incontinence during psychosis were specifically associated with the negative
      psychotic symptom dimension. CONCLUSIONS: Premorbid social impairments are more
      marked in child-and adolescent-onset schizophrenia than in other psychoses. There
      appears to be developmental continuity from premorbid impairment to negative
      symptoms.

PMID- 12509317
TI  - Incidence of schizophrenia in south-east London between 1965 and 1997.
AB  - BACKGROUND: There has been much debate about changes in the incidence of
      schizophrenia. AIMS: To identify any changes in incidence of schizophrenia in
      Camberwell, south-east London, between 1965 and 1997. METHOD: Research Diagnostic
      Criteria and DSM-III-R diagnoses were generated for all first contacts by the
      OPCRIT computer program, and incidence rates of schizophrenia in seven time
      periods were measured. Indirect standardisation and Poisson models were used to
      measure the effect of time period and to examine interactions with age and
      gender. RESULTS: There was a continuous and statistically significant increase in
      the incidence of schizophrenia, which was greatest in people under 35 years of
      age and was not gender-specific. CONCLUSIONS: The incidence of schizophrenia has
      doubled in south-east London over the past three decades.

PMID- 12509318
TI  - Nithsdale Schizophrenia Surveys 24: sexual dysfunction. Case-control study.
AB  - BACKGROUND: That sexual dysfunction occurs in schizophrenia is not in doubt.
      Previous studies have had weaknesses such as the use of selected populations or
      the absence of a control group. AIMS: To measure rates of sexual dysfunction in
      people with schizophrenia compared with the general population. METHOD: Sexual
      dysfunction was assessed by a self-completed gender-specific questionnaire.
      Ninety-eight (73%) of 135 persons with schizophrenia and 81 (71%) of 114 persons
      recruited as controls returned the questionnaire. RESULTS: At least one sexual
      dysfunction was reported by 82% of men and 96% of women with schizophrenia. Male
      patients reported less desire for sex, were less likely to achieve and maintain
      an erection, were more likely to ejaculate more quickly and were less satisfied
      with the intensity of their orgasms. Female patients reported less enjoyment than
      the control group. Sexual dysfunction in female patients was associated with
      negative schizophrenic symptoms and general psychopathology. There was no
      association between sexual dysfunction and type of antipsychotic medication.
      CONCLUSIONS: People with schizophrenia report much higher rates of sexual
      dysfunction than do the general population. Men and women with schizophrenia have
      a different pattern of sexual dysfunction.

PMID- 12509319
TI  - Evaluation of a community-based rehabilitation model for chronic schizophrenia in
      rural India.
AB  - BACKGROUND: There are no community services for the majority of the estimated 10
      million persons with schizophrenia in India. Community-based rehabilitation (CBR)
      is a model of care which has been widely used for physical disabilities in
      resource-poor settings. AIMS: To compare CBR with out-patient care (OPC) for
      schizophrenia in a resource-poor setting in India. METHOD: A longitudinal study
      of outcome in patients with chronic schizophrenia contrasted CBR with OPC.
      Outcome measures were assessed using the Positive and Negative Symptom Scale and
      the modified WHO Disability Assessment Schedule at 12 months. RESULTS:
      Altogether, 207 participants entered the study, 127 in the CBR group and 80 in
      the OPC group. Among the 117 fully compliant participants the CBR model was more
      effective in reducing disability, especially in men. Within the CBR group,
      compliant participants had significantly better outcomes compared with partially
      compliant or non-complaint participants (P<0.001). Although the subjects in the
      CBR group were more socially disadvantaged, they had significantly better
      retention in treatment. CONCLUSIONS: The CBR model is a feasible model of care
      for chronic schizophrenia in resource-poor settings.

PMID- 12509320
TI  - Medical outcome of pregnancy in women with psychotic disorders and their infants
      in the first year after birth.
AB  - BACKGROUND: There has been little research into the health of infants of women
      with psychotic disorders. AIMS: To investigate the antenatal care of mothers with
      a history of psychotic disorders, obstetric outcomes and the subsequent health of
      their babies. METHOD: A matched, controlled cohort study was carried out using
      the General Practice Research Database. Women with a history of a psychotic
      disorder, who gave birth in 1996-1998, were compared with women matched for age
      and general practice (199 cases and 787 controls) and their infants. RESULTS:
      Cases had a higher proportion of stillbirths (OR=4.03, 95% CI 1.14-4.25, P=0.03)
      and neonatal deaths (P<0.001). There was no difference in gestational age at
      antenatal booking. Mothers with psychotic disorders were less likely than
      controls to attend for infant immunisations 90-270 days after birth (RR=0.94, 95%
      CI 0.88-0.99, P=0.03). There was no significant difference in the rates of
      accidents and hospital contacts for infants. CONCLUSIONS: There is an increased
      risk of stillbirth and neonatal death in women with a history of psychotic
      disorder, and it is therefore important for health care professionals to focus on
      optimal obstetric care. The physical health of babies who live with mothers with
      psychotic disorders is not significantly different from that of matched baby
      controls.

PMID- 12509321
TI  - Trends in the use of Part II of the Mental Health Act 1983 in seven English local
      authority areas.
AB  - BACKGROUND: Data collected by the Department of Health show a continuing increase
      in the rate of formal detention in hospital under Part II of the Mental Health
      Act 1983. AIMS: To establish whether the increase in formal detentions is uniform
      across subgroups of the population. METHOD: Data related to use of Part II of the
      Act between 1991 and 1997 collected by seven English local authorities were
      examined. Rates of compulsory admission were standardised to age, gender and
      ethnicity-specific populations. RESULTS: Over the 8-year period the overall rate
      of detention under Part II increased by 32%. It increased in all three major
      ethnic groupings; the rate of increase was greater for men than for women (38%v.
      26%) and, in particular, for younger men compared with younger women (43% v.
      28%). CONCLUSIONS: A combination of factors probably accounts for these findings,
      including service factors (particularly reduction in bed numbers), a culture of
      risk aversion, and changes in the effect of substance misuse on the presentation
      of mental illness.

PMID- 12509322
TI  - Discrimination and delusional ideation.
AB  - BACKGROUND: In the UK and The Netherlands, people with high rates of psychosis
      are chronically exposed to discrimination. AIMS: To test whether perceived
      discrimination is associated longitudinally with onset of psychosis. METHOD: A 3
      year prospective study of cohorts with no history of psychosis and differential
      rates of reported discrimination on the basis of age, gender, disability,
      appearance, skin colour or ethnicity and sexual orientation was conducted in the
      Dutch general population (n=4076). The main outcome was onset of psychotic
      symptoms (delusions and hallucinations). RESULTS: The rate of delusional ideation
      was 0.5% (n=19) in those who did not report discrimination, 0.9% (n=4) in those
      who reported discrimination in one domain, and 2.7% (n=3) in those who reported
      discrimination in more than one domain (exact P=0.027). This association remained
      after adjustment for possible confounders. No association was found between
      baseline discrimination and onset of hallucinatory experiences. CONCLUSIONS:
      Perceived discrimination may induce delusional ideation and thus contribute to
      the high observed rates of psychotic disorder in exposed minority populations.

PMID- 12509323
TI  - Racial discrimination and mental illness.

PMID- 12509324
TI  - Racial discrimination and mental illness.

PMID- 12509325
TI  - Neuroticism and depression.

PMID- 12509326
TI  - Neuroticism and depression.

PMID- 12509327
TI  - Diffuse muscle pain with quetiapine.

PMID- 12509328
TI  - Adjunctive fluvoxamine with clozapine.

PMID- 12509329
TI  - Olanzepine-induced tardive dyskinesia.

PMID- 12509332
TI  - Enhancing the anaerobic response.
AB  - Proteome analysis, and more recently DNA chip technology, has led to the
      identification of a large number of genes that are implicated in the anaerobic
      response of plants. As a result, an increasingly complex picture of the response
      in terms of biochemical and regulatory processes is emerging. A challenge is to
      find out more about the function of these newly identified gene products, and how
      they contribute to flooding tolerance. Our approach has been to manipulate levels
      of candidate gene products (using sense and antisense constructs) in the model
      system Arabidopsis thaliana, combined with biochemical and phenotypic analysis of
      the resulting transgenic plants.

PMID- 12509333
TI  - Molecular and cellular adaptations of maize to flooding stress.
AB  - Anaerobic treatment dramatically alters the patterns of gene expression in maize
      (Zea mays L.) seedlings. During anaerobiosis there is an immediate repression of
      pre-existing protein synthesis, with the concurrent initiation of a selective
      synthesis of approx. 20 proteins. Among these anaerobic proteins are enzymes
      involved in glycolysis and related processes. However, inducible genes that have
      different functions were also found; these may function in other, perhaps more
      long-term, processes of adaptations to flooding, such as aerenchyma formation and
      root-tip death. In this article we review our recent work on maize responses to
      flooding stress, which has addressed two questions: how are these gene expression
      changes initiated and how do they lead to adaptation to flooding stress? Our
      results indicate that an early rise in cytosolic Ca(2+), as well as a quick
      establishment of ionic homeostasis, may be essential for the induction of
      adaptive changes at the cellular as well as organismal level.

PMID- 12509334
TI  - Gene and enhancer trap transposable elements reveal oxygen deprivation-regulated
      genes and their complex patterns of expression in Arabidopsis.
AB  - Transposon tagging with modified maize Ds-GUS constructs was used to isolate
      genes induced by oxygen deprivation in Arabidopsis thaliana. Seedlings of 800
      gene-trap (DsG) and 600 enhancer-trap (DsE) lines were grown on vertically
      positioned plates for 1 week, oxygen deprived for up to 24 h and stained for GUS
      activity. Oxygen deprivation induced intricate patterns of gene expression in
      seedlings of 65 lines. The insertion site and phenotypes of 15 lines were
      examined. Surprisingly, none of the insertions were into genes that encode known
      anaerobic polypeptides. Insertions were identified within or adjacent to genes
      encoding proteins of regulatory, enzymatic, mitochondrial protein import and
      unknown function, as well as adjacent to genes encoding a putative receptor-like
      kinase and putative sensor-histidine kinase. Four lines had significantly lower
      ADH activity after 24 h of oxygen deprivation and three of these showed reduced
      stress tolerance. Two lines with wild-type levels of ADH were low-oxygen
      intolerant. Paradoxically, several lines had significantly higher ADH activity
      after 12 h of oxygen deprivation but reduced stress tolerance. Caffeine
      treatment, which increased ADH specific activity in wild-type seedlings under
      aerobic conditions, was sufficient to increase GUS staining in seven of the 15
      lines, providing evidence that these genes may be regulated by cytosolic calcium
      levels. These results demonstrate the effectiveness of the Ds-GUS tagging system
      in the identification of genes that are regulated in response to oxygen
      deprivation and a calcium second messenger.

PMID- 12509335
TI  - Sugar modulation of alpha-amylase genes under anoxia.
AB  - Tolerance to low oxygen availability is likely to be due to the interaction of
      several factors. Sugar availability is one of the elements required to support
      anaerobic metabolism. In cereal grains the availability of soluble sugars is
      limited, while starch is stored in large amounts. Degradation of starch under
      anoxia is therefore needed to avoid sugar starvation leading to rapid cell death.
      The striking difference in the ability to produce alpha-amylase when comparing
      the anoxia-tolerant rice (Oryza sativa L.) grains with grains of other cereals is
      not easily explained. Rice is able to respond to gibberellins under anoxia, but
      the response is too slow to explain the rapid production of alpha-amylase enzyme.
      In the present work we demonstrated that alpha-amylase production during the
      first 2 d after imbibition is mostly due to the activity of the Ramy3D gene,
      encoding for the G and H isoforms of alpha-amylase. The induction of Ramy3D
      transcription is likely to result from a low sugar content in the grains
      incubated under anoxia. The ability of rice embryos to sense sugars under anoxia
      is reported.

PMID- 12509336
TI  - Light-dependent anaerobic induction of the maize glyceraldehyde-3-phosphate
      dehydrogenase 4 (GapC4) promoter in Arabidopsis thaliana and Nicotiana tabacum.
AB  - The maize glyceraldehyde-3-phosphate dehydrogenase 4 (GapC4) promoter confers
      strong and specific anaerobic gene expression in tobacco (Nicotiana tabacum) and
      potato (Solanum tuberosum). Here we show that the promoter is also anaerobically
      induced in Arabidopsis thaliana. Histochemical analysis demonstrates that the
      promoter is anaerobically induced in roots, leaves, stems and flower organs.
      Surprisingly, the strong anaerobic induction of the promoter is dependent on
      light and on the substitution of oxygen with carbon dioxide. High carbon dioxide
      concentration alone does not induce the promoter in the presence of oxygen and
      light. If anaerobic conditions are generated under complete darkness or if plants
      are submerged, no induction above background is observed. When transgenic tobacco
      harbouring a GapC4 promoter-reporter gene construct is analysed for light
      dependent anaerobic induction, the results are indistinguishable from those with
      arabidopsis. The implications for using the GapC4 promoter as an anaerobic
      reporter for monitoring alterations in the anaerobic signal transduction pathway
      are discussed.

PMID- 12509337
TI  - Functional electron microscopy in studies of plant response and adaptation to
      anaerobic stress.
AB  - This article reviews the contribution made by functional electron microscopy
      towards identifying and understanding the reactions of plant roots and shoots to
      anaerobic stress. Topics examined include: (1) unexpected hypersensitivity,
      rather than hyper-resistance, to anoxia of root tips of flooding-tolerant plants;
      (2) protective, rather than damaging, effects of a stimulated energy metabolism
      (glycolysis and fermentation) under anaerobic conditions; (3) the concept of two
      main strategies of plant adaptation to anaerobic environments, namely avoidance
      of anaerobiosis on the whole plant level, termed 'apparent' tolerance, and
      metabolic adaptation at the cellular and molecular levels, termed 'true'
      tolerance; (4) the importance of protein synthesis during hypoxia and anoxia for
      enhanced energy production and metabolic adaptation; (5) a general adaptive
      syndrome in plants to stress at the ultrastructural level and a possible
      molecular mechanism for its realization under anoxia; (6) the physiological role
      of anaerobically synthesized lipids and nitrate as alternative electron acceptors
      in an oxygen-free medium; and (7) the selection of cell lines derived from callus
      cultures that possess enhanced tolerance to anoxia and can regenerate whole
      plants with improved tolerance of soil waterlogging.

PMID- 12509338
TI  - Plant haemoglobins, nitric oxide and hypoxic stress.
AB  - It is now known that there are several classes of haemoglobins in plants. A
      specialized class of haemoglobins, symbiotic haemoglobins, were discovered 62
      years ago and are found only in nodules of plants capable of symbiotic nitrogen
      fixation. Plant haemoglobins, with properties distinct from symbiotic
      haemoglobins were discovered 18 years ago and are now believed to exist
      throughout the plant kingdom. They are expressed in different organs and tissues
      of both dicot and monocot plants. They are induced by hypoxic stress and by
      oversupply of certain nutrients. Most recently, truncated haemoglobins have been
      shown to also exist in plants. While hypoxic stress-induced haemoglobins are
      widespread in the plant kingdom, their function has not been elucidated. This
      review discusses the recent findings regarding the function of these haemoglobins
      in relation to adaptation to hypoxia in plants. We propose that nitric oxide is
      an important metabolite in hypoxic plant cells and that at least one of the
      functions of hypoxic stress-induced haemoglobins is to modulate nitric oxide
      levels in the cell.

PMID- 12509339
TI  - Antioxidants, oxidative damage and oxygen deprivation stress: a review.
AB  - Oxidative stress is induced by a wide range of environmental factors including UV
      stress, pathogen invasion (hypersensitive reaction), herbicide action and oxygen
      shortage. Oxygen deprivation stress in plant cells is distinguished by three
      physiologically different states: transient hypoxia, anoxia and reoxygenation.
      Generation of reactive oxygen species (ROS) is characteristic for hypoxia and
      especially for reoxygenation. Of the ROS, hydrogen peroxide (H(2)O(2)) and
      superoxide (O(2)(.-)) are both produced in a number of cellular reactions,
      including the iron-catalysed Fenton reaction, and by various enzymes such as
      lipoxygenases, peroxidases, NADPH oxidase and xanthine oxidase. The main cellular
      components susceptible to damage by free radicals are lipids (peroxidation of
      unsaturated fatty acids in membranes), proteins (denaturation), carbohydrates and
      nucleic acids. Consequences of hypoxia-induced oxidative stress depend on tissue
      and/or species (i.e. their tolerance to anoxia), on membrane properties, on
      endogenous antioxidant content and on the ability to induce the response in the
      antioxidant system. Effective utilization of energy resources (starch, sugars)
      and the switch to anaerobic metabolism and the preservation of the redox status
      of the cell are vital for survival. The formation of ROS is prevented by an
      antioxidant system: low molecular mass antioxidants (ascorbic acid, glutathione,
      tocopherols), enzymes regenerating the reduced forms of antioxidants, and ROS
      interacting enzymes such as SOD, peroxidases and catalases. In plant tissues many
      phenolic compounds (in addition to tocopherols) are potential antioxidants:
      flavonoids, tannins and lignin precursors may work as ROS-scavenging compounds.
      Antioxidants act as a cooperative network, employing a series of redox reactions.
      Interactions between ascorbic acid and glutathione, and ascorbic acid and
      phenolic compounds are well known. Under oxygen deprivation stress some
      contradictory results on the antioxidant status have been obtained. Experiments
      on overexpression of antioxidant production do not always result in the
      enhancement of the antioxidative defence, and hence increased antioxidative
      capacity does not always correlate positively with the degree of protection. Here
      we present a consideration of factors which possibly affect the effectiveness of
      antioxidant protection under oxygen deprivation as well as under other
      environmental stresses. Such aspects as compartmentalization of ROS formation and
      antioxidant localization, synthesis and transport of antioxidants, the ability to
      induce the antioxidant defense and cooperation (and/or compensation) between
      different antioxidant systems are the determinants of the competence of the
      antioxidant system.

PMID- 12509340
TI  - Assessment of enzyme induction and aerenchyma formation as mechanisms for
      flooding tolerance in Trifolium subterraneum 'Park'.
AB  - The objective of this study was to evaluate the role of enzyme induction and
      aerenchyma formation in prolonged tolerance to soil flooding in a variety of
      underground clover (Trifolium subterraneum 'Park') previously selected for
      resistance. Seedlings were grown in hydroponic tanks, initially with aeration for
      3 weeks and subsequently in the absence of aeration for up to 3 weeks. After 1 h
      in the absence of aeration, the oxygen concentration in the hydroponic medium had
      decreased to 1.5 %. During the 3 weeks of extreme oxygen deficiency, primary
      roots died and were replaced by considerable numbers of adventitious roots.
      Activities of many glycolytic and fermentative enzymes increased in adventitious
      roots. Excised adventitious roots were capable of immediate induction of ethanol
      in the absence of lactate production, in association with energy charge higher
      than that in excised roots of aerobically maintained controls. Energy charge was
      even higher when measured in adventitious roots in planta. Interestingly,
      haemoglobin protein could be correlated with energy charge. Aerenchyma was
      readily visualized in adventitious roots by optical microscopy of longitudinal
      and transverse sections. We conclude that avoidance of root anoxia via aerenchyma
      is the major mechanism for prolonged root tolerance in Trifolium subterraneum
      'Park'.

PMID- 12509341
TI  - Interactions between plant hormones regulate submergence-induced shoot elongation
      in the flooding-tolerant dicot Rumex palustris.
AB  - Rumex palustris has the capacity to respond to complete submergence with
      hyponastic (upward) growth and stimulated elongation of petioles. These adaptive
      responses allow survival of this plant in habitats with sustained high water
      levels by re-establishing contact with the aerial environment. Accumulated
      ethylene in submerged petioles interacts with ethylene receptor proteins and
      operates as a reliable sensor for the under-water environment. Further downstream
      in the transduction pathway, a fast and substantial decrease of the endogenous
      abscisic acid concentration and a certain threshold level of endogenous auxin and
      gibberellin are required for hyponastic growth and petiole elongation.
      Interactions of these plant hormones results in a significant increase of the in
      vitro cell wall extensibility in submerged petioles. Furthermore, the pattern of
      transcript accumulation of a R. palustris alpha-expansin gene correlated with the
      pattern of petiole elongation upon submergence.

PMID- 12509342
TI  - Paludification and forest retreat in northern oceanic environments.
AB  - Examination of temperature variations over the past century for Europe and the
      Arctic from northern Norway to Siberia suggests that variations in the North
      Atlantic Oscillation are associated with an increase in oceanicity in certain
      maritime regions. A southward depression of the tree line in favour of wet
      heaths, bogs and wetland tundra communities is also observed in northern oceanic
      environments. The physiological basis for this change in ecological succession
      from forest to bog is discussed in relation to the long-term effects of flooding
      on tree survival. The heightened values currently detected in the North Atlantic
      Oscillation Index, together with rising winter temperatures, and increased
      rainfall in many areas in northern Europe, presents an increasing risk of
      paludification with adverse consequences for forest regeneration, particularly in
      areas with oceanic climates. Climatic warming in oceanic areas may increase the
      area covered by bogs and, contrary to general expectations, lead to a retreat
      rather than an advance in the northern limit of the boreal forest. High water
      table levels are not automatically detrimental to forest survival as can be seen
      in swamp, bottom land and mangrove forests. Consequently, the inhibitory effects
      of flooding on tree survival and regeneration in northern regions should not be
      uncritically accepted as merely due to high water levels. Evidence is discussed
      which suggests that physiological and ecological factors may interact to inhibit
      forest regeneration in habitats where there is a risk of prolonged winter
      flooding combined with warmer winters and cool moist summers.

PMID- 12509343
TI  - Physiological and molecular basis of susceptibility and tolerance of rice plants
      to complete submergence.
AB  - Rice plants are much damaged by several days of total submergence. The effect can
      be a serious problem for rice farmers in the rainfed lowlands of Asia, and runs
      contrary to a widespread belief amongst plant biologists that rice is highly
      tolerant of submergence. This article assesses the characteristics of the
      underwater environment that may damage rice plants, examines various
      physiological mechanisms of injury, and reviews recent progress achieved using
      linkage mapping to locate quantitative traits loci (QTL) for tolerance inherited
      from a submergence-tolerant cultivar FR13A. Progress towards identifying the
      gene(s) involved through physical mapping of a dominant tolerance locus on
      chromosome 9 is also summarized. Available physiological evidence points away
      from responses to oxygen shortage as being inextricably involved in submergence
      injury. An imbalance between production and consumption of assimilates is seen as
      being especially harmful, and is exacerbated by strongly accelerated leaf
      extension and leaf senescence that are ethylene-mediated and largely absent from
      FR13A and related cultivars. DNA markers for a major QTL for tolerance are shown
      to be potentially useful in breeding programmes designed to improve submergence
      tolerance.

PMID- 12509344
TI  - Molecular genetics of submergence tolerance in rice: QTL analysis of key traits.
AB  - Flash flooding of young rice plants is a common problem for rice farmers in south
      and south-east Asia. It severely reduces grain yield and increases the
      unpredictability of cropping. The inheritance and expression of traits associated
      with submergence stress tolerance at the seedling stage are physiologically and
      genetically complex. We exploited naturally occurring differences between certain
      rice lines in their tolerance to submergence and used quantitative trait loci
      (QTL) mapping to improve understanding of the genetic and physiological basis of
      submergence tolerance. Three rice populations, each derived from a single cross
      between two cultivars differing in their response to submergence, were used to
      identify QTL associated with plant survival and various linked traits. These
      included total shoot elongation under water, the extent of stimulation of shoot
      elongation caused by submergence, a visual submergence tolerance score, and leaf
      senescence under different field conditions, locations and years. Several major
      QTL determining plant survival, plant height, stimulation of shoot elongation,
      visual tolerance score and leaf senescence each mapped to the same locus on
      chromosome 9. These QTL were detected consistently in experiments across all
      years and in the genetic backgrounds of all three mapping populations. Secondary
      QTL influencing tolerance were also identified and located on chromosomes 1, 2,
      5, 7, 10 and 11. These QTL were specific to particular traits, environments, or
      genetic backgrounds. All identified QTL contributed to increased submergence
      tolerance through their effects on decreased underwater shoot elongation or
      increased maintenance of chlorophyll levels, or on both. These findings establish
      the foundations of a marker-assisted scheme for introducing submergence tolerance
      into agriculturally desirable cultivars of rice.

PMID- 12509345
TI  - Thai jasmine rice carrying QTLch9 (SubQTL) is submergence tolerant.
AB  - Submergence tolerance is an important agronomic trait for rice grown in South
      East Asia, where flash flooding occurs frequently and unpredictably during the
      monsoons. Although mapping locations of one major and several minor quantitative
      trait loci (QTL) were known previously, improving submergence tolerance in
      agronomically desirable types of rice has not been achieved. KDML105 is jasmine
      rice widely grown in rain-fed lowland regions of Thailand. This cultivar is very
      intolerant of submergence stress. To improve submergence tolerance in this
      cultivar, three submergence-tolerant cultivars, FR13A, IR67819F2-CA-61 and
      IR49830-7-1-2-2, were cross-pollinated with KDML105. Transferring the major QTL
      for submergence tolerance was facilitated by four back-crossings to the recipient
      KDML105. Molecular markers tightly linked to the gene(s) involved were developed
      to facilitate molecular genotyping. We demonstrated that individuals of a BC4F3
      line that retained a critical region on chromosome 9 transferred from tolerant
      lines were also tolerant of complete submergence while retaining all the
      agronomically desirable traits of KDML105. In addition, effects of secondary
      QTLch2 were detected statistically in back-cross progenies. Effects of secondary
      QTLch7 were not statistically significant. The close association between tightly
      linked markers of the tolerance locus on chromosome 9 and submergence tolerance
      in the field demonstrates the considerable promise of using these markers in
      lowland rice breeding programmes for selecting increased submergence tolerance.

PMID- 12509346
TI  - Regulation of submergence-induced enhanced shoot elongation in Oryza sativa L.
AB  - Rice (Oryza sativa L.) is the only cereal that can be cultivated in the
      frequently flooded river deltas of South-East and South Asia. The survival
      strategies used by rice have been studied quite extensively and the role of
      several phytohormones in the elongation response has been established. Deep-water
      rice cultivars can diminish flooding stress by rapid elongation of their
      submerged tissues to keep up with the rising waters. Other rice cultivars may
      react by mechanisms of submergence tolerance. Aerenchyma and aerenchymatous
      adventitious roots are formed that facilitate oxygen diffusion to prevent
      anaerobic conditions in the submerged tissues. This paper discusses the molecular
      aspects of the mechanism that leads to shoot elongation (leaves of seedlings and
      internodes), the regulation of which involves metabolism of, and interactions
      between, ethylene, gibberellins and abscisic acid. Finally, the importance of new
      techniques in future research is assessed. Current molecular technology can
      reveal subtle differences in gene activity between tolerant and non-tolerant
      cultivars, and identify genes that are involved in the regulation of submergence
      avoidance and tolerance.

PMID- 12509347
TI  - Responses by coleoptiles of intact rice seedlings to anoxia: k(+) net uptake from
      the external solution and translocation from the caryopses.
AB  - This study evaluated the effects of anoxia on K(+) uptake and translocation in 3
      4-d-old, intact, rice seedlings (Oryza sativa L. cv. Calrose). Rates of net K(+)
      uptake from the medium over 24 h by coleoptiles of anoxic seedlings were
      inhibited by 83-91 %, when compared with rates in aerated seedlings. Similar
      uptake rates, and degree of inhibition due to anoxia, were found for Rb(+) when
      supplied over 1.5-2 h, starting 22 h after imposing anoxia. The Rb(+) uptake
      indicated that intact coleoptiles take up ions directly from the external
      solution. Monovalent cation (K(+) and Rb(+)) net uptake from the solution was
      inhibited by anoxia to the same degree for the coleoptiles of intact seedlings
      and for coleoptiles excised, 'aged', and supplied with exogenous glucose.
      Transport of endogenous K(+) from caryopses to coleoptiles was inhibited less by
      anoxia than net K(+) uptake from the solution, the inhibition being 55 % rather
      than 87 %. Despite these inhibitions, osmotic pressures of sap (pi(sap))
      expressed from coleoptiles of seedlings exposed to 48 h of anoxia, with or
      without exogenous K(+), were 0.66 +/- 0.03 MPa; however, the contributions of
      K(+) to pi(sap) were 23 and 16 %, respectively. After 24 h of anoxia, the K(+)
      concentrations in the basal 10 mm of the coleoptiles of seedlings with or without
      exogenous K(+), were similar to those in aerated seedlings with exogenous K(+).
      In contrast, K(+) concentrations had decreased in aerated seedlings without
      exogenous K(+), presumably due to 'dilution' by growth; fresh weight gains of the
      coleoptile being 3.6- to 4.7-fold greater in aerated than in anoxic seedlings.
      Deposition rates of K(+) along the axes of the coleoptiles were calculated for
      the anoxic seedlings only, for which we assessed the elongation zone to be only
      the basal 4 mm. K(+) deposition in the basal 6 mm was similar for seedlings with
      or without exogenous K(+), at 0.6-0.87 micro mol g(-1) f. wt h(-1). Deposition
      rates in zones above 6 mm from the base were greater for seedlings with, than
      without, exogenous K(+); the latter were sometimes negative. We conclude that for
      the coleoptiles of rice seedlings, anoxia inhibits net K(+) uptake from the
      external solution to a much larger extent than K(+) translocation from the
      caryopses. Furthermore, K(+) concentrations in the elongation zone of the
      coleoptiles of anoxic seedlings were maintained to a remarkable degree,
      contributing to maintenance of pi(sap) in cells of these elongating tissues.

PMID- 12509348
TI  - Dynamic aspects of alcoholic fermentation of rice seedlings in response to
      anaerobiosis and to complete submergence: relationship to submergence tolerance.
AB  - Rice plants are severely damaged by complete submergence. This is a problem in
      rice farming and could be the result, in part, of tissue anoxia imposed by a
      reduced availability of oxygen. To investigate this possibility we monitored
      alcoholic fermentation products as markers for tissue anaerobiosis using
      sensitive laser-based spectroscopy able to sense ethanol and acetaldehyde down to
      3 nl l(-1) and 0.1 nl l(-1), respectively. Acetaldehyde emission began within 0.5
      h of imposing an oxygen-free gas phase environment followed closely by ethanol.
      As treatment progressed, ethanol output increased and came to exceed acetaldehyde
      emission as this stabilized considerably after approx. 3 h. On re-entry of air, a
      sharp post-anaerobic peak of acetaldehyde production was observed. This was found
      to be diagnostic of a preceding anoxic episode of 0.5 h or more. When
      anaerobiosis was lengthened by up to 14 h, the size of the post-anaerobic
      acetaldehyde outburst increased. After de-submergence from oxygen-free water, a
      similarly strong but slower post-anaerobic acetaldehyde upsurge was seen, which
      was accompanied by an increase in ethanol emission. Light almost, but not
      completely, eliminated fermentation in anaerobic surroundings and also the post
      anaerobic or post-submergence peaks in acetaldehyde production. All
      photosynthetically generated oxygen was consumed within the plant. There was no
      substantial difference in acetaldehyde and ethanol output between FR13A and the
      less submergence-tolerant line CT6241 under any submergence treatment. In some
      circumstances, submergence damaged CT6241 more than FR13A even in the absence of
      vigorous fermentation. We conclude that oxygen deprivation may not always
      determine the extent of damage caused to rice plants by submergence under natural
      conditions.

PMID- 12509349
TI  - Contrasting effects of submergence in light and dark on pyruvate decarboxylase
      activity in roots of rice lines differing in submergence tolerance.
AB  - Submergence tolerance of 13 doubled haploid lines of rice and their parents
      (submergence tolerant FR13A and submergence intolerant CT6241) was assessed using
      2-week-old seedlings. Plants were scored for leaf senescence and percentage of
      seedlings that survived up to 15 d submergence, followed by a 12 d recovery
      period. Seven lines proved to be submergence tolerant, and six relatively
      intolerant. In all lines, activity of pyruvate decarboxylase (PDC), extracted
      from the apical 3-5 cm of root axes, decreased by 46-96 % and 38-76 %,
      respectively, during 5 or 10 d submergence under natural day/night conditions,
      compared with pre-submergence values (100 %). However, when the enzyme was
      extracted at night, submergence increased PDC activity of all rice lines (approx.
      112 % on average), compared with pre-submergence values (100 %). The stimulating
      effect of the dark period on PDC activity was reproduced and amplified by
      submerging rice seedlings for up to 5 d in continuous darkness in water
      containing sub-ambient concentrations of oxygen (2.3 mg l(-1)). Such increased
      PDC activity was also observed in seedlings exposed to anoxia for 6 h (approx. 6
      175 % higher than pre-submergence values). Irrespective of tolerance class,
      submergence decreased soluble protein concentrations under all conditions and
      sampling times. No positive correlation was found between PDC activity and
      tolerance of the various rice lines to submergence. However, PDC activity was
      slightly higher in submergence intolerant lines, compared with tolerant lines,
      under both dark submergence and anoxia. Such differences in PDC activity between
      the two groups of rice lines were not observed when they were submerged under the
      natural diurnal cycle. Increased PDC activity in roots at night demonstrated a
      probable incidence of tissue hypoxia or anoxia during submergence during each
      dark period.

PMID- 12509350
TI  - Aerenchyma and an inducible barrier to radial oxygen loss facilitate root
      aeration in upland, paddy and deep-water rice (Oryza sativa L.).
AB  - The present study evaluated waterlogging tolerance, root porosity and radial O(2)
      loss (ROL) from the adventitious roots, of seven upland, three paddy, and two
      deep-water genotypes of rice (Oryza sativa L.). Upland types, with the exception
      of one genotype, were as tolerant of 30 d soil waterlogging as the paddy and deep
      water types. In all but one of the 12 genotypes, the number of adventitious roots
      per stem increased for plants grown in waterlogged, compared with drained, soil.
      When grown in stagnant deoxygenated nutrient solution, genotypic variation was
      evident for root porosity and rates of ROL, but there was no overall difference
      between plants from the three cultural types. Adventitious root porosity
      increased from 20-26 % for plants grown in aerated solution to 29-41 % for plants
      grown in stagnant solution. Growth in stagnant solution also induced a 'tight'
      barrier to ROL in the basal regions of adventitious roots of five of the seven
      upland types, all three paddy types, and the two deep-water types. The enhanced
      porosity provided a low resistance pathway for O(2) movement to the root tip, and
      the barrier to ROL in basal zones would have further enhanced longitudinal O(2)
      diffusion towards the apex, by diminishing losses to the rhizosphere. The
      plasticity in root physiology, as described above, presumably contributes to the
      ability of rice to grow in diverse environments that differ markedly in soil
      waterlogging, such as drained upland soils as well as waterlogged paddy fields.

PMID- 12509351
TI  - Mutational analysis of the interaction between 14-3-3 proteins and plant plasma
      membrane H+-ATPase.
AB  - In this study, we report on mutational studies performed to investigate the
      mechanism of binding of 14-3-3 proteins to the plasma membrane H(+)-ATPase of
      plant cells. In fact, although the molecular basis of the interaction between 14
      3-3 and the known mode-1 and mode-2 consensus sequences are well characterized,
      no information is available regarding the association with the H(+)-ATPase, which
      contains the novel binding site YTV totally unrelated to the 14-3-3 canonical
      motifs. To this purpose, different mutants of the maize 14-3-3 GF14-6 isoform
      were produced and used in interaction studies with the plasma membrane H(+)
      ATPase and with a peptide reproducing the 14-3-3 binding site of the enzyme. The
      ability of 14-3-3 mutants to stimulate H(+)-ATPase activity was also tested. To
      investigate the mechanism of fusicoccin-dependent interaction, binding
      experiments between 14-3-3 proteins and mutants of the extreme portion of the
      H(+)-ATPase C terminus were also carried out. The results demonstrate that
      mutations of Lys(56) and Val(185) within the amphipathic groove disrupt the
      ability of GF14-6 to interact with H(+)-ATPase and to stimulate its activity.
      Moreover, substitution of Asp(938) and Asp(940) in the MHA2 H(+)-ATPase C
      terminus greatly decreased association with GF14-6, thereby demonstrating a
      crucial role of negatively charged residues in the fusicoccin-dependent
      interaction.

PMID- 12509352
TI  - A proposal for electronic medical records in U.S. primary care.
AB  - Delivery of excellent primary care-central to overall medical care-demands that
      providers have the necessary information when they give care. This paper,
      developed by the National Alliance for Primary Care Informatics, a collaborative
      group sponsored by a number of primary care societies, argues that providers' and
      patients' information and decision support needs can be satisfied only if primary
      care providers use electronic medical records (EMRs). Although robust EMRs are
      now available, only about 5% of U.S. primary care providers use them. Recently,
      with only modest investments, Australia, New Zealand, and England have achieved
      major breakthroughs in implementing EMRs in primary care. Substantial benefits
      realizable through routine use of electronic medical records include improved
      quality, safety, and efficiency, along with increased ability to conduct
      education and research. Nevertheless, barriers to adoption exist and must be
      overcome. Implementing specific policies can accelerate utilization of EMRs in
      the U.S.

PMID- 12509353
TI  - A two-way messaging system to enhance antiretroviral adherence.
AB  - Failure to adhere to complex antiretroviral regimens can lead to resistance and
      treatment failure among HIV-positive persons. In this study of the feasibility of
      an automated two-way messaging system to improve adherence, participants received
      multiple short daily messages designed to remind, educate, encourage adherence,
      and solicit responses concerning side effects and self-reported adherence. Twenty
      five participants remained in the study for a median of 208 days, receiving
      17,440 messages and replying to 14,677 (84%). Participants reported missing one
      or more doses on 36% of 743 queries and reported medication side effects on 26%
      of 729 queries. Participants expressed high satisfaction with the messaging
      system and reported that it helped with medication adherence. The study suggests
      that it is feasible to use an automated wireless two-way messaging system to
      communicate with HIV-positive patients over an extended period of time.

PMID- 12509354
TI  - Design and pilot evaluation of an internet smoking cessation program.
AB  - Relatively little is known about how to use the Internet to promote health
      behavioral change. This article describes a multiple-contact Internet smoking
      cessation program with an 8-week web-based course, online tools for self
      monitoring of behaviors, and computer-tailored e-mail messages timed to
      enrollees' quit efforts. In a pilot study in 49 smokers, we found that enrollees
      returned to the website a median of 2 times and completed an average of 2 of 8
      educational modules. In follow-up, respondents (n = 26) rated e-mail and web
      components of the intervention as equally valuable (5.9 vs. 5.5 of 10, p = 0.44).
      While site had potentially important effects on smoking behaviors (34% of
      enrollees either quit smoking or had a 50% reduction in cigarette use), we were
      not able hold the interest of the majority of enrollees over the intervention
      period. Problems with the design of the site are discussed.

PMID- 12509355
TI  - Integrating query of relational and textual data in clinical databases: a case
      study.
AB  - OBJECTIVES: The authors designed and implemented a clinical data mart composed of
      an integrated information retrieval (IR) and relational database management
      system (RDBMS). DESIGN: Using commodity software, which supports interactive,
      attribute-centric text and relational searches, the mart houses 2.8 million
      documents that span a five-year period and supports basic IR features such as
      Boolean searches, stemming, and proximity and fuzzy searching. MEASUREMENTS:
      Results are relevance-ranked using either "total documents per patient" or
      "report type weighting." RESULTS: Non-curated medical text has a significant
      degree of malformation with respect to spelling and punctuation, which creates
      difficulties for text indexing and searching. Presently, the IR facilities of
      RDBMS packages lack the features necessary to handle such malformed text
      adequately. CONCLUSION: A robust IR+RDBMS system can be developed, but it
      requires integrating RDBMSs with third-party IR software. RDBMS vendors need to
      make their IR offerings more accessible to non-programmers.

PMID- 12509356
TI  - Development of visual diagnostic expertise in pathology -- an information
      processing study.
AB  - OBJECTIVE: To identify key features contributing to trainees' development of
      expertise in microscopic pathology diagnosis, a complex visual task, and to
      provide new insights to help create computer-based training systems in pathology.
      DESIGN: Standard methods of information-processing and cognitive science were
      used to study diagnostic processes (search, perception, reasoning) of 28 novices,
      intermediates, and experts. Participants examined cases in breast pathology; each
      case had a previously established gold standard diagnosis. Videotapes correlated
      the actual visual data examined by participants with their verbal "think-aloud"
      protocols. MEASUREMENTS: Investigators measured accuracy, difficulty, certainty,
      protocol process frequencies, error frequencies, and times to key diagnostic
      events for each case and subject. Analyses of variance, chi-square tests and post
      hoc comparisons were performed with subject as the unit of analysis. RESULTS:
      Level of expertise corresponded with differences in search, perception, and
      reasoning components of the tasks. Several discrete steps occur on the path to
      competence, including development of adequate search strategies, rapid and
      accurate recognition of anatomic location, acquisition of visual data
      interpretation skills, and transitory reliance on explicit feature
      identification. CONCLUSION: Results provide the basis for an empirical cognitive
      model of competence for the complex tasks of microscopic pathology diagnosis.
      Results will inform the development of computer-based pedagogy tools in this
      domain

PMID- 12509357
TI  - Comparing computer-interpretable guideline models: a case-study approach.
AB  - OBJECTIVES: Many groups are developing computer-interpretable clinical guidelines
      (CIGs) for use during clinical encounters. CIGs use "Task-Network Models" for
      representation but differ in their approaches to addressing particular modeling
      challenges. We have studied similarities and differences between CIGs in order to
      identify issues that must be resolved before a consensus on a set of common
      components can be developed. DESIGN: We compared six models: Asbru, EON, GLIF,
      GUIDE, PRODIGY, and PROforma. Collaborators from groups that created these models
      represented, in their own formalisms, portions of two guidelines: American
      College of Chest Physicians cough guidelines [correction] and the Sixth Report of
      the Joint National Committee on Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure. MEASUREMENTS: We compared the models according to eight
      components that capture the structure of CIGs. The components enable modelers to
      encode guidelines as plans that organize decision and action tasks in networks.
      They also enable the encoded guidelines to be linked with patient data-a key
      requirement for enabling patient-specific decision support. RESULTS: We found
      consensus on many components, including plan organization, expression language,
      conceptual medical record model, medical concept model, and data abstractions.
      Differences were most apparent in underlying decision models, goal
      representation, use of scenarios, and structured medical actions. CONCLUSION: We
      identified guideline components that the CIG community could adopt as standards.
      Some of the participants are pursuing standardization of these components under
      the auspices of HL7.

PMID- 12509358
TI  - Factors affecting and affected by user acceptance of computer-based nursing
      documentation: results of a two-year study.
AB  - OBJECTIVES: The documentation of the nursing process is an important but often
      neglected part of clinical documentation. Paper-based systems have been
      introduced to support nursing process documentation. Frequently, however,
      problems such as low quality of documentation are reported. It is unclear whether
      computer-based documentation systems can reduce these problems and which factors
      influence their acceptance by users. DESIGN: We introduced a computer-based
      nursing documentation system on four wards of the University Hospitals of
      Heidelberg and systematically evaluated its preconditions and its effects in a
      pretest-posttest intervention study. For the analysis of user acceptance, we
      concentrated on subjective data drawn from questionnaires and interviews.
      MEASUREMENTS: A questionnaire was developed using items from published
      questionnaires and items that had to be developed for the special purpose of this
      study. RESULTS: The quantitative results point to two factors influencing the
      acceptance of a new computer-based documentation system: the previous acceptance
      of the nursing process and the previous amount of self-confidence when using
      computers. On one ward, the diverse acceptance scores heavily declined after the
      introduction of the nursing documentation system. Explorative qualitative
      analysis on this ward points to further success factors of computer-based nursing
      documentation systems. CONCLUSION: Our results can be used to assist the planning
      and introduction of computer-based nursing documentation systems. They
      demonstrate the importance of computer experience and acceptance of the nursing
      process on a ward but also point to other factors such as the fit between nursing
      workflow and the functionality of a nursing documentation system.

PMID- 12509359
TI  - Speech recognition as a transcription aid: a randomized comparison with standard
      transcription.
AB  - OBJECTIVE: Speech recognition promises to reduce information entry costs for
      clinical information systems. It is most likely to be accepted across an
      organization if physicians can dictate without concerning themselves with real
      time recognition and editing; assistants can then edit and process the computer
      generated document. Our objective was to evaluate the use of speech-recognition
      technology in a randomized controlled trial using our institutional
      infrastructure. DESIGN: Clinical note dictation from physicians in two specialty
      divisions was randomized to either a standard transcription process or a speech
      recognition process. Secretaries and transcriptionists also were assigned
      randomly to each of these processes. MEASUREMENTS: The duration of each dictation
      was measured. The amount of time spent processing a dictation to yield a finished
      document also was measured. Secretarial and transcriptionist productivity,
      defined as hours of secretary work per minute of dictation processed, was
      determined for speech recognition and standard transcription. RESULTS:
      Secretaries in the endocrinology division were 87.3% (confidence interval, 83.3%,
      92.3%) as productive with the speech-recognition technology as implemented in
      this study as they were using standard transcription. Psychiatry
      transcriptionists and secretaries were similarly less productive. Author,
      secretary, and type of clinical note were significant (p < 0.05) predictors of
      productivity. CONCLUSION: When implemented in an organization with an existing
      document-processing infrastructure (which included training and interfaces of the
      speech-recognition editor with the existing document entry application), speech
      recognition did not improve the productivity of secretaries or transcriptionists.

PMID- 12509360
TI  - The use of computers for clinical care: a case series of advanced U.S. sites.
AB  - OBJECTIVE: To describe advanced clinical information systems in the context in
      which they have been implemented and are being used. DESIGN: Case series of five
      U.S. hospitals, including inpatient, ambulatory and emergency units. Descriptive
      study with data collected from interviews, observations, and document analysis.
      MEASUREMENTS: The use of computerized results, notes, orders, and event monitors
      and the type of decision support; data capture mechanisms and data form; impact
      on clinician satisfaction and clinical processes and outcomes; and the
      organizational factors associated with successful implementation. RESULTS: All
      sites have implemented a wide range of clinical information systems with
      extensive decision support. The systems had been well accepted by clinicians and
      have improved clinical processes. Successful implementation required leadership
      and long-term commitment, a focus on improving clinical processes, and gaining
      clinician involvement and maintaining productivity. CONCLUSION: Despite
      differences in approach there are many similarities between sites in the clinical
      information systems in use and the factors important to successful
      implementation. The experience of these sites may provide a valuable guide for
      others who are yet to start, or are just beginning, the implementation of
      clinical information systems.

PMID- 12509362
TI  - Clinical management of urinary tract infection in women: a prospective cohort
      study.
AB  - BACKGROUND: It is unclear how symptoms of urinary tract infection (UTI) influence
      clinical management in terms of diagnostic testing and treatment with
      antibiotics. OBJECTIVES: Our aim was to assess how 11 symptoms associated with
      UTI related to the probability of being tested (near patient test or urine
      culture) or treated with antibiotics by their GP, and to see if the same 11
      symptoms were associated with (i) confirmed infection from urine culture and (ii)
      re-consultation complaining of the same symptoms within 1 month. METHODS: A
      prospective cohort study of 160 patients consulting their GP with symptoms of UTI
      in eight general practices in Avon, UK was carried out. Association between
      symptoms and the probability of being (i) tested by the near patient test, (ii)
      tested by urine culture or (iii) treated empirically with antibiotics were
      examined. The association between symptoms and the probability of being treated
      empirically or tested (near patient test or mid-stream urine) was examined.
      Likelihood ratios for symptoms and near patient test results compared with two
      'gold standards' for diagnosis of UTI were calculated and their impact on post
      test probability of UTI determined. RESULTS: GPs were far more likely to treat
      empirically patients with symptoms of dysuria and frequency [odds ratio (OR)
      6.50, 95% confidence interval (CI) 2.02-20.89] or dysuria alone (OR 5.24, 95% CI
      1.62-16.95). They were far less likely to perform diagnostic tests in patients
      with dysuria and frequency (OR for near patient testing 0.34, 95% CI 0.14-0.83;
      OR for urine culture 0.15, 95% CI 0.04-0.56). The prior probabilities of UTI were
      25% (positive urine culture) and 29% (re-consultation within 1 month),
      respectively, for each of the 'gold standards' used. Individual symptoms and near
      patient tests did not raise the posterior probability of UTI irrespective of
      which 'gold standard' was used. The most useful symptom was a history of vomiting
      (likelihood ratio 2.96, 95% CI 0.3-31.2), but this occurred in only three
      patients. CONCLUSIONS: Current clinical practice results in a large proportion of
      patients receiving unnecessary antibiotic treatment. Individual symptoms of UTI
      are an inadequate guide on which to base diagnostic testing and antibiotic
      treatment decisions in primary care. Either this diagnostic inaccuracy should be
      acknowledged as an inevitable part of clinical practice or more accurate clinical
      prediction rules that incorporate symptoms, signs and near patient test results
      that are applicable in everyday clinical practice are required.

PMID- 12509363
TI  - Prevalence of three lower urinary tract symptoms in men-a population-based study.
AB  - BACKGROUND: Lower urinary tract symptoms are a common and costly public health
      issue. In earlier studies, the prevalence of urinary symptoms can be seen to
      fluctuate because there is no consensus about how to define and categorize the
      severity of the symptoms. OBJECTIVES: The study was undertaken in order to
      investigate the prevalence of three common lower urinary tract symptoms (urgency,
      stress incontinence and post-micturition dribbling) and analyse health care
      seeking behaviour. METHODS: A self-administered questionnaire was developed to
      investigate all men aged 40-80 years residing in the community of Surahammar,
      Sweden. The questionnaire included items on three specific urinary symptoms:
      urgency, stress incontinence and post-micturition dribbling, and one question
      about health care-seeking behaviour. RESULTS: A response rate of 86% was obtained
      in the questionnaire study. The overall prevalence of the lower urinary tract
      symptoms was 24%. The prevalence increased from 20% in the group aged 40-49 years
      to 28% in the group aged 70-80 years (P < 0.01). Post-micturition dribbling (21%)
      was the most frequent symptom, and stress incontinence (2.4%) was the least
      frequent symptom. The number of participants who sought health care was low (4%)
      and increased significantly with age (P < 0.001). CONCLUSIONS: The present study
      showed that 24% of the Swedish cohort of men of 40-80 years of age reported at
      least one of the following symptoms: urgency, stress incontinence or post
      micturition dribbling. This study is consistent with other research regarding the
      low consultation frequency for these symptoms. Moreover, the study is also in
      accord with those findings indicating that for the majority of men with urinary
      symptoms, their health care providers are not aware of their problem.

PMID- 12509364
TI  - Discussing STIs: doctors are from Mars, patients from Venus.
AB  - BACKGROUND: Primary care plays an important role in promoting sexual health, but
      in this setting counselling regarding sexually transmitted infections (STIs) is
      rarely performed and often inadequate. OBJECTIVE: Our aim was to identify and
      quantify the barriers physicians encounter in discussing STIs with their
      patients. METHODS: A postal questionnaire-based survey was carried out in a
      random sample of 200 primary care physicians in Antwerp, Belgium. RESULTS: The
      response rate was 68%. Among the 122 respondents, only 44.3% provide some form of
      counselling (asking about sexual history, informing about safe sex or informing
      about STIs) regularly, at least once a week. Major barriers are language and
      comprehension problems (for 74.2% of respondents), ethnic differences (68.4%),
      insufficient training (69.4%), lack of time (60.8%), presence of the patient's
      partner (89.2%) or mother (94.2%), first contact with a patient (60.8%), fear of
      embarrassing the patient (30.6%) and a patient without genital complaints
      (71.4%). About half of the GPs fail to counsel an asymptomatic patient with
      obvious STI risk, and as many give no safe sex advice in a first contraception
      consultation. CONCLUSIONS: Physicians have many and various barriers to
      discussing STIs with their patients. Features of contemporary STI counselling and
      solutions to its problems are discussed. Education of health care providers
      should be given priority.

PMID- 12509365
TI  - Is treatment of atrial fibrillation in primary care based on thromboembolic risk
      assessment?
AB  - BACKGROUND: Antithrombotic treatment in atrial fibrillation should be guided by
      the risk of thromboembolic events. Although practice studies have shown
      underutilization of antithrombotics, it is not clear whether physicians make use
      of thromboembolic risk stratification in their treatment decisions, as
      recommended in current guidelines. OBJECTIVE: The aim of the present study was to
      assess which clinical determinants influence coumarin and aspirin prescription in
      patients with atrial fibrillation in primary care. METHODS: In a cross-sectional
      study of 15 computerized general practices covering 38 000 patients in The
      Netherlands, we identified patients with atrial fibrillation using several search
      algorithms. Determinants of antithrombotic therapy were assessed using polytomous
      logistic regression analysis. RESULTS: A total of 247 patients with atrial
      fibrillation were identified among 10 335 patients aged 55 years or over
      (prevalence 2.4%). Mean age was 77 years (range 55-95); 51% were male. Overall,
      52% of the patients used coumarin and 27% used aspirin. About 50% of patients
      were also treated by a cardiologist. Referred patients were prescribed coumarin
      more often (63% versus 35%, P < 0.001). Prior stroke/transient ischaemic attack
      or systemic embolism [adjusted odds ratio (OR) 5.3, 95% confidence interval (CI)
      1.1-24.8], and chronic heart failure (adjusted OR 2.1, 95% CI 0.8-5.1) were
      independent determinants for coumarin prescription. These associations were less
      strong for aspirin prescription. However, other established risk factors for
      future thromboembolic events, such as hypertension and diabetes mellitus, did not
      lead to higher prescription rates. In contrast, several factors not associated
      with thromboembolic events, such as chronic (versus paroxysmal) atrial
      fibrillation (adjusted OR 3.7, 95% CI 1.7-8.2) and longstanding (versus recent)
      diagnosis (adjusted OR 2.2, 95% CI 1.1-4.5), were also associated with higher
      coumarin prescription. CONCLUSION: These results illustrate that physicians'
      decisions about initiating antithrombotic therapy in atrial fibrillation are not
      evidence based. They are guided partly by thromboembolic risk stratification, but
      also by factors insignificant for thromboembolic risk.

PMID- 12509366
TI  - Gender, age and deprivation differences in the primary care management of
      hypertension in Scotland: a cross-sectional database study.
AB  - BACKGROUND: Little is known about the community management of cardiovascular
      disease among different gender, age or deprivation groups, even though much of
      the long-term treatment takes place within primary care. OBJECTIVES: Our aim was
      to determine whether important gender, age and deprivation differences exist in
      the primary care management of hypertension. METHODS: A cross-sectional analysis
      of computerized general practice data was carried out in 43 practices in Scotland
      contributing to the Continuous Morbidity Recording project. The main outcome
      measures were odds ratios of being under GP review; receiving different classes
      of antihypertensive treatments [thiazides, beta-blockers, angiotensin-converting
      enzyme (ACE) inhibitors, calcium channel blockers]; and receiving other
      cardiovascular preventative treatments (statins and/or antiplatelets). RESULTS:
      Compared with males, female hypertensive patients were more likely to receive a
      thiazide and less likely to be given an ACE inhibitor, calcium channel blocker or
      secondary preventative treatment. Elderly hypertensive patients were less likely
      than the youngest patients to be under GP active review, more likely to be on a
      thiazide, calcium channel blocker or antiplatelet treatment, and less likely to
      be on a statin. More deprived hypertensive patients were less likely to be under
      GP review, or to be on a thiazide or a statin, but were more likely to be on a
      calcium channel blocker or an antiplatelet drug than the most affluent group.
      CONCLUSIONS: Important gender, age and deprivation differences exist in three
      important components of the primary care treatment of hypertension in Scotland.

PMID- 12509367
TI  - Prophylactic treatment after myocardial infarction in primary care: how far can
      we go?
AB  - BACKGROUND: Despite best practice, it may not be achievable in some patients to
      reach the optimal goals of secondary prevention recommendations for various
      reasons, such as co-morbidity, contraindications for some drugs or side effects.
      OBJECTIVE: Our aim was to estimate the achievable standards for audit purposes in
      primary care for prophylactic treatment of secondary prevention of myocardial
      infarction. METHODS: We conducted a survey of consecutive patients with a
      hospital diagnosis of first acute myocardial infarction during 1997 who were
      identified from discharge books from four hospitals and interviewed at their
      primary health centre 2 years after admission. The achievable standard for a
      prophylactic drug was then defined as the proportion of patients that could
      benefit from the treatment excluding those that for one justified reason or
      another were off medication. RESULTS: Three hundred and sixty-nine patients were
      interviewed in the follow-up. Aspirin or another antiplatelet regimen was
      prescribed in 86.9 patients, beta-blockers in 50.2%, angiotensin-converting
      enzyme (ACE) inhibitors in 32.5% and lipid-lowering drugs in 52%. The estimated
      achievable standards for those prescribed drugs were 94.5, 71,8, 50.5 and 69.8%,
      respectively. CONCLUSIONS: There is an underuse of prophylactic drug therapies
      after myocardial infarction. The standards established in this study for
      secondary preventive drug treatment might be achieved through a reasonable effort
      by GPs working in primary care committed to improving the quality of care.

PMID- 12509368
TI  - Quality of life and objective disease criteria in patients with intermittent
      claudication in general practice.
AB  - BACKGROUND: The quality of life (QoL) of patients with chronic diseases is an
      important decision criterion for medical treatment, especially in primary care
      settings. It is known that subjective sickness feelings often cannot be
      correlated with objective disease criteria. OBJECTIVE: The aim of the study was
      to determine the QoL of patients with intermittent claudication with the arterial
      morphology, haemodynamic parameters and functional disability of peripheral
      arterial occlusive disease (PAOD). METHODS: In 150 patients with stable
      intermittent claudication, the health-related QoL was compared with the angiogram
      score, the resting Doppler pressure values, and the initial claudication distance
      (ICD) and absolute claudication distance (ACD) with treadmill exercise. RESULTS:
      The QoL did not correlate significantly with either the angiogram score or the
      ankle systolic blood pressure and ankle brachial index. ICD and ACD correlated
      significantly with the QoL activity subscales of pain, complaints and functional
      status (P < 0.001). In a multiple regression analysis, ACD and body mass index
      were the most predictive variables for the QoL. CONCLUSION: The QoL of PAOD
      patients is independent of the peripheral Doppler pressure and the angiographic
      severity of the disease. The most important criterion for the QoL is the
      patient's functional disability.

PMID- 12509369
TI  - The provision of 'same-day' care in general practice: an observational study.
AB  - BACKGROUND: Surveys suggest that general practice is perceived to be
      inaccessible, with long delays before it is possible to be seen by a doctor.
      Although there is demand for rapid access to care, this has the potential to
      decrease continuity of care, which research consistently shows to be valued by
      patients but stressful for doctors. OBJECTIVE: Our aim was to investigate the
      provision of 'same-day' care and the characteristics, treatment expectations and
      priorities of patients attending for 'routine' and 'same-day' appointments.
      METHODS: The uptake of same-day and routine appointments was determined from
      appointment system records. A self-completed questionnaire survey of people
      attending 362 same-day and 362 routine appointments at 15 general practices in
      Avon and Gloucestershire enabled comparisons with respect of patient
      characteristics and consultation experiences, patients' preferences for rapid
      access, seeing a known practitioner or seeing a doctor rather than a nurse.
      RESULTS: The uptake per 1000 practice population per day was 7.6 [95% confidence
      interval (CI) 7.1-8.1] for routine appointments and 3.8 (95% CI 3.5-4.2) for same
      day appointments. In univariable analyses, use of same-day care was greater by
      people who were younger, non-white, in work and with educational qualifications.
      They had attended the practice less often, waited less time to see a doctor
      previously, had their current problem for a shorter time and were more likely to
      expect a prescription. From multivariable analyses, only age, speed of previously
      obtaining appointments, expecting a prescription and having the problem for a
      short time were independently associated with receiving same-day care. Rapid
      access to care was rated as more important than seeing a known doctor for two
      clinical scenarios. CONCLUSIONS: Much care is provided currently on the day it is
      requested in general practice. The use of same-day care was related to acute
      illness and expectations but was not associated with deprivation or patient
      characteristics apart from age.

PMID- 12509370
TI  - Welfare rights advice in primary care: prevalence, processes and specialist
      provision.
AB  - BACKGROUND: Despite persistent poverty-related health inequalities, few sustained
      responses have been developed in primary care. Welfare rights provision has been
      proposed as one potential pathway to addressing health inequalities. OBJECTIVES:
      This study was set up to address the prevalence of welfare rights issues in
      general practice, and the practitioner response to unmet need. METHODS: A postal
      questionnaire was sent to practitioners in GP surgeries of an inner city health
      authority with high levels of deprivation. By means of a 'most recent case
      audit', data on welfare advice needs were collected. Practices with in-house
      welfare rights provision were compared with those surgeries with no such
      provision. RESULTS: Questionnaires were returned by 153 practitioners, describing
      their most recent case with a welfare rights need (mean 10.41 days ago). Of the
      respondents, 70.6% felt that there was a mental health element to this
      consultation, 49.8% of problems were described as urgent, and 65.8% of patients
      requested information or guidance. Those practitioners with specialist advisers
      in the surgery (n = 81) were significantly more likely to find referring patients
      to advisers easy, that quality of advice for patients was good, that welfare
      providers enhanced their ability to practice effectively and that such provision
      improves the health and well-being of patients. In those surgeries without
      provision (n = 72), patients were more likely to approach their practitioner for
      advice. GPs were more likely than nurses and other practising staff to see a case
      with welfare rights needs. Practitioners were more likely to raise the welfare
      issues if they had specialist advice in the surgery. CONCLUSIONS: A large amount
      of practitioner consultation time is spent on welfare rights-related issues.
      Although practitioners are skilled in detecting need, and their practice is
      enhanced by specialist support, expansion is needed to provide the advice which
      cannot be met by clinical consultation.

PMID- 12509371
TI  - Identification of patients attending accident and emergency who may be suitable
      for treatment by a pharmacist.
AB  - BACKGROUND: Several studies have demonstrated that 25-40% of Accident & Emergency
      department attendances are for conditions that could be managed by the patient's
      general practitioner. The number of these who could be appropriately managed by a
      community pharmacist, has not previously been established. OBJECTIVE: To
      establish the frequency with which patients attend an inner city A&E department
      with problems that could be managed by a community pharmacist. METHODS: A cross
      sectional, retrospective review of A&E records for adult patients (>16 years) was
      conducted during the first two weeks of March 1999. Application of recognised
      criteria identified patients whose conditions were suitable for treatment by a
      pharmacist. Associated patient characteristics were investigated. RESULTS: During
      the study period 2636 adult patients attended the A&E department. Pharmacist
      management was considered appropriate in 8% of adult attendances (95% CI 6.8
      8.9). The most commonly presented symptoms considered appropriate for pharmacist
      treatment included those of upper respiratory, gastrointestinal and pain
      conditions and reflect those previously identified in the literature.
      CONCLUSIONS: A pharmacist could manage an estimated 8% of adult attendances at
      this A&E department. Efforts should be made to increase the awareness of the
      general public of the role of a community pharmacist to reduce demand on A&E and
      GP services.

PMID- 12509372
TI  - Factors influencing home visits in Slovenian general practice.
AB  - BACKGROUND: There is great variability in home visiting rates in Europe. The
      European General Practice Research Workshop (EGPRW) has conducted a pilot
      quantitative international study on home visits and developed a questionnaire,
      which has not yet been tested on a national level. In Slovenia, home visiting is
      decreasing, but the factors influencing home visiting by GPs in the country have
      not yet been examined. OBJECTIVES: The purpose of this study was to test the
      feasibility of the questionnaire on home visiting developed by EGPRW and to study
      home visiting in Slovenia. METHODS: A random representative sample of 165
      Slovenian GPs were given a questionnaire, developed on the basis of former EGPRW
      projects. Each of the respondents provided data on 10 consecutive home visits
      made during office hours, data on his/her practice and number of consultations
      during the registration period. Multivariate modelling of home visits per working
      week as the dependent variable was performed. RESULTS: A 71% response rate was
      achieved, and the data from 1151 requests for home visits and 1015 completed home
      visits were analysed. The average number of home visits per working week was 2.5,
      with wide variation among the respondents (0-10, SD 1.89). Older GPs, trainees,
      GPs from rural areas and those with a higher proportion of elderly patients
      carried out more home visits. The selected logistic regression model fits the
      data well according to established criteria. CONCLUSION: It is possible to use
      the questionnaire developed by EGPRW on a national scale and to obtain
      representative valid national data. The home visiting rate in Slovenia is low
      compared with rates in other countries. Rural location of practice, GP's age,
      trainee status and the number of older patients on the list are the most
      important predictors of the home visiting rate.

PMID- 12509373
TI  - Influences on GPs' decision to prescribe new drugs-the importance of who says
      what.
AB  - OBJECTIVES: The aim of this study was to understand the range of factors that
      influence GPs' uptake of new drugs METHODS: A total of 107 GPs selected
      purposively from high, medium and low new drug prescribing practices in two
      health authorities in the north west of England were interviewed using the
      critical incident technique with semi-structured interviews. Interview topics
      included reasons for prescribing new drugs launched between January 1998 and May
      1999; reasons for prescribing the new drug rather than alternatives; and sources
      of information used for each prescribed drug. RESULTS: Important biomedical
      influences were the failure of current therapy and adverse effect profile. More
      influential than these, however, was the pharmaceutical representative. Hospital
      consultants and observation of hospital prescribing was cited next most
      frequently. Patient request for a drug, and patient convenience and acceptability
      were also likely to influence new drug uptake. Written information was of limited
      importance except for local guidelines. GPs were largely reactive and
      opportunistic recipients of new drug information, rarely reporting an active
      information search. The decision to initiate a new drug is heavily influenced by
      'who says what', in particular the pharmaceutical industry, hospital consultants
      and patients. The decision to 'adopt' a new drug is clinched by subsequent
      personal clinical experience. CONCLUSIONS: Prescribing of new drugs is not simply
      related to biomedical evaluation and critical appraisal but, more importantly, to
      the mode of exposure to pharmacological information and social influences on
      decision making. Viewed within this broad context, prescribing variation becomes
      more understandable. Findings have implications for the implementation of
      evidence-based medicine, which requires a multifaceted approach.

PMID- 12509374
TI  - Understanding variation in quality improvement: the treatment of sore throats in
      primary care.
AB  - BACKGROUND: In 1988, two practices attempted to improve the prescribing of
      antibiotics for sore throat. The initiative produced only modest improvements in
      prescribing practice, a finding the authors found difficult to explain. This
      paper reanalyses the data from an audit of antibiotic prescribing for sore throat
      in general practice. OBJECTIVE: Our aim was to demonstrate the use of Shewhart
      control charts and to obtain fresh insight into the variations in clinical
      practice revealed in clinical audit data. METHODS: We use Shewhart control charts
      to explore variation in antibiotic prescribing between GPs and to suggest the
      action most likely to result in improvement. RESULTS: Using control charts, it is
      possible to distinguish two categories of GPs: low prescribers of antibiotics and
      high prescribers of antibiotics. Low prescribers of antibiotics show common cause
      variation, indicating that their prescribing is a stable process. Among low
      prescribers, improvement can best be achieved by changing the common underlying
      process. One high prescriber of antibiotics is affected by special cause
      variation. Among high prescribers, improvement can best be achieved by
      investigating the special causes affecting this GP and learning lessons from the
      findings. CONCLUSION: The original improvement effort took the same action on all
      GPs in both practices. Our analysis suggests that such an approach was unlikely
      to be successful and that different actions were needed for high and low
      prescribers. The control charts provide fresh insights on the original data and
      guide improvement efforts.

PMID- 12509375
TI  - Quality improvement of integrated child health care management after in-service
      training for physicians.
AB  - OBJECTIVE: The aim of the present study was to evaluate the quality of integrated
      child health care management (ICHCM) promoted by the World Health Organization
      (WHO) after an in-service training course. METHODS: The training was carried out
      in a rural and an urban health unit and in the paediatric ward of the local
      reference hospital. Tutorial courses were given to small groups (4-6 students)
      over a 5-day period (40 h in total). The courses consisted of demonstrations,
      discussions, analyses, applications and evaluations of the ICHCM (in-service
      training). The training was evaluated by comparing the quality of ICHCM given by
      each physician in their work place on three different occasions: 15 days before
      the course began (pre-course evaluation), 15 days after the course (post-course
      evaluation) and 6 months after the course had ended (follow-up evaluation). Each
      physician was observed in each period during his or her consultation with a child
      under 5 years of age who presented with acute diarrhoea or acute respiratory
      infection. A series of possible behaviours by physicians was checked against a
      list of behaviours that would indicate effective training. RESULTS: The average
      grades obtained by the 24 physicians evaluated (pre- and post-course) increased
      from 74.5 to 96.6 (22.1 points, P < 0.01). Physicians whose baseline grade was
      <80 had the greatest increases. Their averages grades increased from 68.2 to 91.3
      (23.1 points, P < 0.001). The overall change for the whole group was sustained
      for up to 6 months (post-course 96.6 points and follow-up 90.9 points, P > 0.05).
      CONCLUSION: The quality of ICHCM improved after the in-service training. No
      additional resources were necessary in the clinical units. This type of training
      can be extended to other countries or health programmes.

PMID- 12509376
TI  - Randomizing patients by family practice: sample size estimation, intracluster
      correlation and data analysis.
AB  - BACKGROUND: Cluster randomized controlled trials increasingly are used to
      evaluate health interventions where patients are nested within larger clusters
      such as practices, hospitals or communities. Patients within a cluster may be
      similar to each other relative to patients in other clusters on key variables;
      therefore, sample size calculations and analyses of results require special
      statistical methods. OBJECTIVE: The purpose of this study was to illustrate the
      calculations used for sample size estimation and data analysis and to provide
      estimates of the intraclass correlation coefficients (ICCs) for several variables
      using data from the Seniors Medication Assessment Research Trial (SMART), a
      community-based trial of pharmacists consulting to family physicians to optimize
      the drug therapy of older patients. METHODS: The study was a paired cluster
      randomized trial, where the family physician's practice was the cluster. The
      sample size calculation was based on a hypothesized reduction of 15% in mean
      daily units of medication in the intervention group compared with the control
      group, using an alpha of 0.05 (one-tailed) with 80% power, and an ICC from pilot
      data of 0.08. ICCs were estimated from the data for several variables. The
      analyses comparing the two groups used a random effects model for a meta-analysis
      over pairs. RESULTS: The design effect due to clustering was 2.12, resulting in
      an inflation in sample size from 340 patients required using individual
      randomization, to 720 patients using randomization of practices, with 15 patients
      from each of 48 practices. ICCs for medication use, health care utilization and
      general health were <0.1; however, the ICC for mean systolic blood pressure over
      the trial period was 0.199. CONCLUSIONS: Compared with individual randomization,
      cluster randomization may substantially increase the sample size required to
      maintain adequate statistical power. The differences in ICCs among potential
      outcome variables reinforce the need for valid estimates to ensure proper study
      design.

PMID- 12509377
TI  - How evidence based are recruitment strategies to randomized controlled trials in
      primary care? Experience from seven studies.
AB  - BACKGROUND: Failure to recruit adequate numbers of participants represents a
      major barrier to the completion of randomized controlled trials in primary care
      and is associated with substantial opportunity costs. However, uncertainty exists
      regarding the relative effectiveness of different methods to promote recruitment.
      OBJECTIVES: The purpose of this study was to estimate the proportion of
      strategies used to promote patient recruitment to randomized controlled trials in
      primary care that are evidence based. METHODS: Investigators from seven primary
      care-based clinical trials of dyspepsia management aiming to recruit a total of
      6070 patients participated. Following a survey of trial organization, a Delphi
      technique was used to reach consensus on levels of evidence on the effectiveness
      of interventions or organizational characteristics in influencing recruitment.
      The main outcome measures were the proportions of interventions or organizational
      characteristics for influencing patient recruitment that are based upon
      randomized controlled trials, on convincing non-experimental evidence or meeting
      neither of these criteria. RESULTS: Out of a total of 56 interventions used
      across the trials, 35 (63%) were judged as evidence based. Out of a total of 29
      organizational characteristics possessed by the trials, five (17%) were judged as
      evidence based. Across the seven dyspepsia trials, the presence of 'favourable'
      organizational characteristics appeared to be important contributors towards
      successful recruitment. CONCLUSIONS: A wide range of interventions and
      organizational characteristics with the potential to promote recruitment were
      used or possessed by seven primary care trials. Many were not evidence based. Our
      experience suggests that organizational characteristics could be more influential
      in trial recruitment than the use of specific interventions. Given the costs of
      primary care-based trials, researchers need more rigorous evidence to inform
      recruitment strategies.

PMID- 12509378
TI  - Perceptions of risk of cervical cancer and attitudes towards cervical screening.

PMID- 12509379
TI  - Contraceptive use by medical students whilst on holiday.

PMID- 12509380
TI  - 'Sokkor': research into the contextual facilitators barriers involved in the
      management of patients with type 2 diabetes mellitus must now intensify extend
      into all cultures worldwide.

PMID- 12509381
TI  - Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody
      rituximab is effective and well tolerated: results of a phase 2 trial of the
      German Hodgkin Lymphoma Study Group.
AB  - This phase 2 trial was performed to evaluate the safety and efficacy of the
      chimeric monoclonal anti-CD20 antibody rituximab in patients with relapsed
      lymphocyte-predominant Hodgkin lymphoma or other CD20(+) subtypes of Hodgkin
      disease (HD). Eligibility criteria required expression of the CD20 antigen on
      more than 30% of malignant cells. Fourteen patients were treated with 4 weekly
      intravenous infusions of rituximab (375 mg/m(2)). All patients had at least one
      prior chemotherapy (median, 2). The median time from first diagnosis was 9 years.
      Adverse events, such as rhinitis, fever, chills, and nausea, were usually
      transient and of mild to moderate grade, allowing outpatient treatment in most
      cases. All patients completed treatment and were eligible for a response. The
      overall response in 14 assessable patients was 86%, with 8 complete remissions
      and 4 partial remissions, and 2 patients with progressive disease. At a median
      follow-up of 12 months, 9 of 12 responders were in remission. The median duration
      of response has not been reached yet (20+ months). We conclude that rituximab is
      both safe and effective in a subgroup of CD20(+) patients with HD.

PMID- 12509382
TI  - HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in
      diffuse large B-cell lymphoma.
AB  - We have cloned and characterized a novel human gene, HGAL (human germinal center
      associated lymphoma), which predicts outcome in patients with diffuse large B
      cell lymphoma (DLBCL). The HGAL gene comprises 6 exons and encodes a cytoplasmic
      protein of 178 amino acids that contains an immunoreceptor tyrosine-based
      activation motif (ITAM). It is highly expressed in germinal center (GC)
      lymphocytes and GC-derived lymphomas and is homologous to the mouse GC-specific
      gene M17. Expression of the HGAL gene is specifically induced in B cells by
      interleukin-4 (IL-4). Patients with DLBCL expressing high levels of HGAL mRNA
      demonstrate significantly longer overall survival than do patients with low HGAL
      expression. This association was independent of the clinical international
      prognostic index. High HGAL mRNA expression should be used as a prognostic factor
      in DLBCL.

PMID- 12509383
TI  - BCR-ABL independence and LYN kinase overexpression in chronic myelogenous
      leukemia cells selected for resistance to STI571.
AB  - Clinical studies have shown that the tyrosine kinase inhibitor STI571 effectively
      controls BCR-ABL-positive chronic myelogenous leukemia (CML). However, disease
      progression while on STI571 therapy has been reported, suggesting de novo or
      intrinsic resistance to BCR-ABL-targeted therapy. To investigate possible
      mediators of acquired STI571 resistance, K562 cells resistant to 5 microM STI571
      (K562-R) were cloned and compared to the parental cell population. K562-R cells
      had reduced BCR-ABL expression and limited activation of BCR-ABL signaling
      cascades (Stat 5, CrkL, MAPK). STI571 failed to activate caspase cascades or to
      suppress expression of survival genes (bcl-xL) in resistant cells. Gene
      sequencing and tyrosine kinase activity measurements demonstrated that K562-R
      cells retained wild-type and active BCR-ABL tyrosine kinase that was inhibitable
      by in vitro incubation with STI571, suggesting that BCR-ABL was not coupled to
      proliferation or survival of K562-R cells. The src-related kinase LYN was highly
      overexpressed and activated in K562-R cells, and its inhibition reduced
      proliferation and survival of K562-R cells while having limited effects of K562
      cells. Specimens taken from patients with advanced CML that progressed on STI571
      therapy also were analyzed for LYN kinase expression, and they were found to be
      elevated to a level similar to that of K562-R cells. Comparison of samples from
      patients taken prior to and following STI571 failure suggested that expression
      and/or activation of LYN/HCK occurs during disease progression. Together, these
      results suggest that acquired STI571 resistance may be associated with BCR-ABL
      independence and mediated in part through overexpression of other tyrosine
      kinases.

PMID- 12509384
TI  - Reduced-intensity allogeneic hematopoietic stem cell transplantation with
      alemtuzumab conditioning regimens: survival does not plateau until after day 200.

PMID- 12509385
TI  - Myelodysplastic subclones in chronic myeloid leukemia: implications for imatinib
      mesylate therapy.

PMID- 12509386
TI  - A modified Folts model or the original Folts model to evaluate new
      antithrombotics?

PMID- 12509387
TI  - Monoclonal myelopoiesis and subnormal erythropoietin concentration are
      independent risk factors for thromboembolic complications in essential
      thrombocythemia.

PMID- 12509388
TI  - Implications of effects in placebo groups.

PMID- 12509389
TI  - Biological significance of interventions that change breast density.

PMID- 12509390
TI  - In clinical trials and in the clinic, what is the placebo's effect?

PMID- 12509391
TI  - European groups oppose Myriad's latest patent on BRCA1.

PMID- 12509392
TI  - NIH workshop tries to create consensus on HRT use.

PMID- 12509393
TI  - Tobacco use a leading global cancer risk, report says.

PMID- 12509394
TI  - Stat bite: global cigarette consumption, 1880-2000.

PMID- 12509395
TI  - NCI adopts interim funding policies until budget is approved.

PMID- 12509396
TI  - Pitfalls in the use of DNA microarray data for diagnostic and prognostic
      classification.

PMID- 12509397
TI  - Placebo effects in oncology.
AB  - BACKGROUND: Previous studies have suggested that placebo treatment can have
      positive effects on a variety of disorders and disease-related symptoms. However,
      the methodology used to collect and interpret the data may not have been ideal,
      because the studies were not double-blinded or the endpoints were not properly
      validated. The purpose of the present study was to determine the probability of
      improvement in symptoms or quality of life and tumor response in cancer patients
      treated with placebos in randomized controlled trials. We hypothesized that
      administration of placebos would improve symptom control and quality of life but
      would not lead to tumor response. METHODS: We reviewed reports of randomized
      controlled trials in which there was a placebo arm (37 trials) or a best
      supportive care (BSC) arm (10 trials). RESULTS: In trials that assessed average
      responses for patients in the placebo arm, improvements in average levels of pain
      were reported in two of six trials and in appetite, in one of seven trials. No
      improvements in average levels of weight gain (six trials), in quality of life
      (as assessed by patients; 10 trials), or in performance status (as assessed by
      physicians; nine trials) were reported. In trials that assessed response to a
      placebo in individual patients, 0%-21% of patients showed reduced pain or
      decreased analgesic intake, 8%-27% of patients showed appetite improvement, 7%
      17% of patients showed weight gain, and 6%-14% of patients showed improvement in
      performance status. Quality of life for individual patients was not reported in
      any trial. Tumor response assessed by World Health Organization criteria was
      observed in 10 (2.7%) of 375 patients (seven trials total). Response as assessed
      by a serum marker was observed in 1 (1.7%) of 60 patients (two trials total). The
      probability of symptom improvement in patients receiving BSC was generally
      similar to that in patients receiving placebo, although no improvement in pain
      and only one tumor response among 191 patients (five trials) were reported.
      CONCLUSION: In randomized double-blinded, placebo-controlled trials, presumably
      with minimum sources of bias, placebos are sometimes associated with improved
      control of symptoms such as pain and appetite but rarely with positive tumor
      response. Substantial improvements in symptoms and quality of life are unlikely
      to be due to placebo effects.

PMID- 12509398
TI  - Postmenopausal hormone therapy and change in mammographic density.
AB  - BACKGROUND: Mammographic density is an independent risk factor for breast cancer.
      Postmenopausal hormone use is associated with an increase in mammographic
      density, but the magnitude of the density increase is unknown. METHODS: Baseline
      and 12-month mammograms were obtained for 571 (65%) of the 875 women, aged 45-64
      years, who were enrolled in the Postmenopausal Estrogen/Progestin Interventions
      Trial and randomly assigned to receive placebo, daily conjugated equine estrogens
      at 0.625 mg/day (CEE), daily CEE and medroxyprogesterone acetate (MPA) at 10
      mg/day on days 1-12 (CEE+MPA-cyclic), daily CEE and MPA at 2.5 mg/day (CEE+MPA
      continuous), or daily CEE and micronized progesterone (MP) at 200 mg/day on days
      1-12 (CEE+MP). We analyzed digitized mammograms to determine the percentage of
      the left breast that was composed of dense tissue (i.e., mammographic percent
      density). Linear regression analysis was used to examine the effects of
      treatments on the change in mammographic percent density between baseline and 12
      months, before and after adjustment for possible confounders. All statistical
      tests were two-sided. RESULTS: The adjusted absolute mean changes in mammographic
      percent density over 12 months were 4.76% (95% confidence interval [CI] = 3.29%
      to 6.23%), 4.58% (95% CI = 3.19% to 5.97%), and 3.08% (95% CI = 1.65% to 4.51%)
      for women in the CEE+MPA-cyclic, CEE+MPA-continuous, and CEE-MP groups,
      respectively. Each of those absolute mean changes was statistically significantly
      different from the adjusted absolute mean change in mammographic percent density
      for women in the placebo group, which was -0.07% (95% CI = -1.50% to 1.38%).
      CONCLUSION: Greater mammographic density was associated with the use of
      estrogen/progestin combination therapy, regardless of how the progestin was
      given, but not with the use of estrogen only.

PMID- 12509399
TI  - Trends in U.S. pleural mesothelioma incidence rates following simian virus 40
      contamination of early poliovirus vaccines.
AB  - BACKGROUND: Poliovirus vaccines that were used during the late 1950s and early
      1960s were contaminated with simian virus 40 (SV40), a monkey virus that is
      tumorigenic in rodents. SV40 DNA sequences have been detected in some human
      cancers, especially pleural mesotheliomas, although results are conflicting. We
      examined the relationship between SV40-contaminated poliovirus vaccine exposure
      and subsequent rates of pleural mesothelioma in the United States. METHODS: We
      used data from the Surveillance, Epidemiology, and End Results Program to
      estimate age- and sex-specific pleural mesothelioma incidence rates per 10(5)
      person-years (py) from 1975 through 1997 and the Poisson distribution to
      determine 95% confidence intervals (CIs) for each rate. The prevalence, by birth
      cohort, of poliovirus vaccine exposure during the period of widespread SV40
      contamination was determined from published survey data. Trends in mesothelioma
      incidence rates were assessed by examining age- and sex-specific rates over
      calendar periods and with the use of the age-period-cohort model. Trends in
      mesothelioma incidence were then compared with trends in prevalence of exposure.
      All statistical tests were two-sided. RESULTS: The age-standardized pleural
      mesothelioma incidence rate for 1975 through 1997 was 1.29/10(5) py (95% CI =
      1.24/10(5) to 1.34/10(5) py) in males and 0.21/10(5) py (95% CI = 0.20/10(5) to
      0.23/10(5) py) in females. The rate in males increased from 0.79/10(5) py (95% CI
      = 0.62/10(5) to 1.0/10(5) py) in 1975 to a peak of 1.69/10(5) py (95% CI =
      1.46/10(5) to 1.95/10(5) py) in 1992. Incidence rates increased the most among
      males who were 75 years of age or older, the age group least likely to have been
      immunized against poliovirus. Incidence rates among males in the age groups most
      heavily exposed to SV40-contaminated poliovirus vaccine remained stable or
      decreased from 1975 through 1997. Similar age-specific trends were observed among
      females. The age-period-cohort models for men and women also indicated that the
      trends in pleural mesothelioma incidence were not related to trends in exposure
      to SV40-contaminated poliovirus vaccine. CONCLUSIONS: Age-specific trends in U.S.
      pleural mesothelioma incidence rates are not consistent with an effect of
      exposure to SV40-contaminated poliovirus vaccine. Nonetheless, given reports of
      the detection of SV40 genomic DNA sequences in human mesotheliomas, monitoring of
      vaccine-exposed cohorts should continue.

PMID- 12509400
TI  - Baseline cytology, human papillomavirus testing, and risk for cervical neoplasia:
      a 10-year cohort analysis.
AB  - BACKGROUND: Annual Pap smear screening has been favored over less frequent
      screening in the United States to minimize the risk of cervical cancer. We
      evaluated whether simultaneous screening with a Pap test and human papillomavirus
      (HPV) testing is useful for assessing the risk for cervical intraepithelial
      neoplasia (CIN) 3 or cervical cancer. METHODS: We enrolled 23 702 subjects in a
      study of HPV infection at Kaiser Permanente, Northwest Division, Portland, OR.
      Data were analyzed for 20 810 volunteers who were at least 16 years old (mean =
      35.9 years) with satisfactory baseline Pap tests and suitable samples for HPV
      testing. Women were followed for up to 122 months (from April 1, 1989, to June
      30, 1999) to determine the risk for histopathologically confirmed CIN3 or cancer.
      RESULTS: Among 171 women with CIN3 or cancer diagnosed over 122 months, 123
      (71.9%, 95% confidence interval [CI] = 65.2% to 78.7%) had baseline Pap results
      of atypical squamous cells or worse and/or a positive HPV test, including 102
      (86.4%, 95% CI = 80.3% to 92.6%) of the 118 cases diagnosed within the first 45
      months of follow-up. During this 45-month period, the cumulative incidence of
      CIN3 or cancer was 4.54% (95% CI = 3.61% to 5.46%) among women with a Pap test
      result of atypical squamous cells or worse, positive HPV tests, or both compared
      with 0.16% (95% CI = 0.08% to 0.24%) among women with negative Pap and HPV tests.
      Age, screening behavior, a history of cervical cancer precursors, and a history
      of treatment for CIN minimally affected results. CONCLUSIONS: Negative baseline
      Pap and HPV tests were associated with a low risk for CIN3 or cancer in the
      subsequent 45 months, largely because a negative HPV test was associated with a
      decreased risk of cervical neoplasia. Negative combined test results should
      provide added reassurance for lengthening the screening interval among low-risk
      women, whereas positive results identify a relatively small subgroup that
      requires more frequent surveillance.

PMID- 12509401
TI  - Essential role of phosphatidylinositol 3-kinase-dependent CCAAT/enhancer binding
      protein beta activation in the induction of glutathione S-transferase by
      oltipraz.
AB  - BACKGROUND: Cancer chemopreventive agents transcriptionally induce genes whose
      protein products can protect cells from chemical-induced carcinogenesis.
      Oltipraz, a dithiolthione, exerts chemopreventive responses through glutathione S
      transferase (GST) induction. We investigated the role of the CCAAT/enhancer
      binding protein (C/EBP) in the induction of the GSTA2 gene (alpha class) by
      oltipraz and identified the enhancer element(s) responsible for GSTA2 gene
      expression. METHODS: H4IIE rat hepatocyte-derived cells were treated with
      oltipraz, and GSTA2 expression was determined by northern and immunoblot
      analyses. The activation of C/EBPbeta and alpha forms and NF-E2-related factor 2
      (Nrf2) was assessed by immunochemical assays. C/EBPbeta-DNA binding activity was
      determined by subcellular fractionation and electrophoretic mobility shift
      assays. The role of the C/EBP binding site in the induction of the GSTA2 gene was
      assessed by luciferase reporter-gene activity. The role of phosphatidylinositol 3
      kinase (PI3-kinase) and mitogen-activated protein (MAP) kinase signaling pathways
      in C/EBP-mediated GSTA2 induction was studied by using chemical inhibitors,
      overexpression vectors, and dominant-negative mutants. All statistical tests were
      two-sided. RESULTS: Oltipraz induced GSTA2 mRNA and protein expression. In
      oltipraz-treated cells, C/EBPbeta translocated to the nucleus and bound to the
      consensus sequence of C/EBP (TTGCGCAA). Oltipraz treatment increased luciferase
      reporter-gene activity in H4IIE cells transfected with the C/EBP-containing
      regulatory region of the GSTA2 gene. Deletion of the C/EBP binding site or
      overexpression of a dominant-negative mutant form of C/EBP (AC/EBP) abolished the
      reporter gene activity. PI3-kinase, but not MAP kinases, was required for
      C/EBPbeta-dependent induction of GSTA2 by oltipraz. CONCLUSIONS: Oltipraz-induced
      GSTA2 gene expression is dependent upon PI3-kinase-mediated nuclear translocation
      and binding of C/EBPbeta to the C/EBP response element in the GSTA2 gene
      promoter.

PMID- 12509402
TI  - Insulin resistance and prostate cancer risk.
AB  - Because high waist-to-hip ratio (WHR) and high serum insulin levels have been
      reported to be associated with an increased risk of prostate cancer, we assessed
      the relationship between insulin resistance and prostate cancer risk in Chinese
      men. We measured fasting serum glucose and insulin levels in 128 case and 306
      control subjects and used the homeostasis model assessment to derive indices of
      insulin sensitivity and resistance. Relative to men in the lowest tertiles, men
      in the highest tertile of insulin sensitivity had a reduced risk of prostate
      cancer (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.21 to 0.60), but
      men in the highest tertile of insulin resistance had an increased risk of
      prostate cancer (OR = 2.78, 95% CI = 1.63 to 4.72). Considering insulin
      resistance and WHR together, the effect of insulin resistance was apparent in all
      tertiles of WHR, with men in the highest tertile of insulin resistance and WHR
      having the highest risk (OR = 8.21, 95% CI = 2.84 to 23.70). The associations
      between prostate cancer risk and insulin sensitivity or resistance were
      independent of total caloric intake and serum levels of insulin-like growth
      factors, sex hormones, and sex hormone-binding globulin. Because of the
      retrospective design of this study, the role of insulin resistance in prostate
      cancer needs to be confirmed in prospective studies.

PMID- 12509403
TI  - Tumor location and detection of k-ras mutations in stool from colorectal cancer
      patients.

PMID- 12509405
TI  - Re: On the use of familial aggregation in population-based case probands for
      calculating penetrance.

PMID- 12509406
TI  - Re: On the use of familial aggregation in population-based case probands for
      calculating penetrance.

PMID- 12509407
TI  - Re: On the use of familial aggregation in population-based case probands for
      calculating penetrance.

PMID- 12509408
TI  - Re: On the use of familial aggregation in population-based case probands for
      calculating penetrance.

PMID- 12509410
TI  - Re: On the use of familial aggregation in population-based case probands for
      calculating penetrance.

PMID- 12509411
TI  - Beta-carotene and lung cancer: a lesson for future chemoprevention
      investigations?

PMID- 12509412
TI  - Effects of mutations of ABCA1 in the first extracellular domain on subcellular
      trafficking and ATP binding/hydrolysis.
AB  - ABCA1 mediates release of cellular cholesterol and phospholipid to form high
      density lipoprotein (HDL). The three different mutants in the first extracellular
      domain of human ABCA1 associated with Tangier disease, R587W, W590S, and Q597R,
      were examined for their subcellular localization and function by using ABCA1-GFP
      fusion protein stably expressed in HEK293 cells. ABCA1-GFP expressed in HEK293
      was fully functional for apoA-I-mediated HDL assembly. Immunostaining and
      confocal microscopic analyses demonstrated that ABCA1-GFP was mainly localized to
      the plasma membrane (PM) but also substantially in intracellular compartments.
      All three mutant ABCA1-GFPs showed no or little apoA-I-mediated HDL assembly.
      R587W and Q597R were associated with impaired processing of oligosaccharide from
      high mannose type to complex type and failed to be localized to the PM, whereas
      W590S did not show such dysfunctions. Vanadate-induced nucleotide trapping was
      examined to elucidate the mechanism for the dysfunction in the W590S mutant.
      Photoaffinity labeling of W590S with 8-azido-[alpha-(32)P]ATP was stimulated by
      adding ortho-vanadate in the presence of Mn(2+) as much as in the presence of
      wild-type ABCA1. These results suggest that the defect of HDL assembly in R587W
      and Q597R is due to the impaired localization to the PM, whereas W590S has a
      functional defect other than the initial ATP binding and hydrolysis.

PMID- 12509413
TI  - ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading
      through protein kinase Calpha and RhoA.
AB  - The ADAMs (a disintegrin and metalloprotease) comprise a large family of
      multidomain proteins with cell-binding and metalloprotease activities. The ADAM12
      cysteine-rich domain (rADAM12-cys) supports cell attachment using syndecan-4 as a
      primary cell surface receptor that subsequently triggers beta(1) integrin
      dependent cell spreading, stress fiber assembly, and focal adhesion formation.
      This process contrasts with cell adhesion on fibronectin, which is integrin
      initiated but syndecan-4-dependent. In the present study, we investigated
      ADAM12/syndecan-4 signaling leading to cell spreading and stress fiber formation.
      We demonstrate that syndecan-4, when present in significant amounts, promotes
      beta(1) integrin-dependent cell spreading and stress fiber formation in response
      to rADAM12-cys. A mutant form of syndecan-4 deficient in protein kinase C
      (PKC)alpha activation or a different member of the syndecan family, syndecan-2,
      was unable to promote cell spreading. GF109203X and Go6976, inhibitors of PKC,
      completely inhibited ADAM12/syndecan-4-induced cell spreading. Expression of
      syndecan-4, but not syn4DeltaI, resulted in the accumulation of activated beta(1)
      integrins at the cell periphery in Chinese hamster ovary beta1 cells as revealed
      by 12G10 staining. Further, expression of myristoylated, constitutively active
      PKCalpha resulted in beta(1) integrin-dependent cell spreading, but additional
      activation of RhoA was required to induce stress fiber formation. In summary,
      these data provide novel insights into syndecan-4 signaling. Syndecan-4 can
      promote cell spreading in a beta(1) integrin-dependent fashion through PKCalpha
      and RhoA, and PKCalpha and RhoA likely function in separate pathways.

PMID- 12509414
TI  - A noncontiguous, intersubunit binding site for calmodulin on the skeletal muscle
      Ca2+ release channel.
AB  - Both apocalmodulin (Ca(2+)-free calmodulin) and Ca(2+)-calmodulin bind to and
      regulate the activity of skeletal muscle Ca(2+) release channel (ryanodine
      receptor, RYR1). Both forms of calmodulin protect sites after amino acids 3630
      and 3637 on RYR1 from trypsin cleavage. Only apocalmodulin protects sites after
      amino acids 1982 and 1999 from trypsin cleavage. Ca(2+)-calmodulin and
      apocalmodulin both bind to two different synthetic peptides representing amino
      acids 3614-3643 and 1975-1999 of RYR1, but Ca(2+)-calmodulin has a higher
      affinity than apocalmodulin for both peptides. Cysteine 3635, within the 3614
      3643 sequence of RYR1, can form a disulfide bond with a cysteine on an adjacent
      subunit within the RYR1 tetramer. The second cysteine is now shown to be between
      amino acids 2000 and 2401. The close proximity of the cysteines forming the
      intersubunit disulfide to the two sites that bind calmodulin suggests that
      calmodulin is binding at a site of intersubunit contact, perhaps with one lobe
      bound between amino acids 3614 and 3643 on one subunit and the second lobe bound
      between amino acids 1975 and 1999 on an adjacent subunit. This model is
      consistent with the finding that Ca(2+)-calmodulin and apocalmodulin each bind to
      a single site per RYR1 subunit (Rodney, G. G., Williams, B. Y., Strasburg, G. M.,
      Beckingham, K., and Hamilton, S. L. (2000) Biochemistry 39, 7807-7812).

PMID- 12509415
TI  - Cisplatin induces endoplasmic reticulum stress and nucleus-independent apoptotic
      signaling.
AB  - DNA damage is believed to be the main cause of the antiproliferative effect of
      cisplatin, a cornerstone agent in anticancer therapy. However, cisplatin can be
      expected to react also with nucleophiles other than DNA. Using enucleated cells
      (cytoplasts) we demonstrate here that cisplatin-induced apoptotic signaling may
      occur independently of DNA damage. Cisplatin-induced caspase-3 activation in
      cytoplasts required calcium and the activity of the calcium-dependent protease
      calpain. It is known that calpain activation may be associated with endoplasmic
      reticulum (ER) stress, suggesting that the ER is a cytosolic target of cisplatin.
      Consistent with this hypothesis, cisplatin induced calpain-dependent activation
      of the ER-specific caspase-12 in cytoplasts as well as in intact cells. Cisplatin
      also induced increased expression of Grp78/BiP, another marker of ER stress. By
      contrast, the DNA-damaging topoisomerase II inhibitor etoposide did not induce
      apoptotic signaling in cytoplasts nor ER stress in intact cells. We have thus
      identified a novel mechanism of action of cisplatin. The results have
      implications for the understanding of resistance mechanisms as well as the unique
      efficiency of this drug.

PMID- 12509416
TI  - Dual function of an amino-terminal amphipatic helix in androgen receptor-mediated
      transactivation through specific and nonspecific response elements.
AB  - Steroid receptors are transcription factors that, upon binding to their response
      elements, regulate the expression of several target genes via direct protein
      interactions with transcriptional coactivators. For the androgen receptor,
      additional interactions between the amino- and carboxyl-terminal regions have
      been reported. The first amino acids of the amino-terminal domain are necessary
      for this amino/carboxyl-terminal interaction. Deletion of a FQNLF core sequence
      in this region blunts the interaction, as does a G21E mutation. We investigated
      the effect of the aforementioned mutations in the context of the full size
      androgen receptor on a series of selective and nonselective androgen response
      elements. Strikingly, the FQNLF deletion strongly reduced the androgen receptor
      capacity to transactivate through nonselective motifs but did not affect its
      activity on selective elements. Although the G21E mutation strongly impairs the
      amino/carboxyl-terminal interaction, it does not significantly influence androgen
      receptor activity on either selective or nonselective elements. Surprisingly,
      this mutation leads to an increased binding of the amino-terminal domain to the
      glutamine-rich region of the steroid receptor coactivator-1 of the p160 family.
      Taken together, these data suggest that the amino-terminal amino acids of the
      androgen receptor play a key role in determining its transcriptional activity by
      modulating the interaction with the ligand-binding domain as well as interaction
      with p160 coactivators.

PMID- 12509417
TI  - The Clf1p splicing factor promotes spliceosome assembly through N-terminal
      tetratricopeptide repeat contacts.
AB  - Spliceosome assembly follows a well conserved pathway of subunit addition that
      includes both small nuclear ribonucleoprotein (snRNP) particles and non-snRNP
      splicing factors. Clf1p is an unusual splicing factor composed almost entirely of
      direct repeats of the tetratricopeptide repeat (TPR) protein-binding motif. Here
      we show that the Clf1p protein resides in at least two multisubunit protein
      complexes, a small nuclear RNA-free structure similar to what was reported as the
      Prp19p complex (nineteen complex; NTC) and an RNP structure that contains the U2,
      U5, and U6 small nuclear RNAs. Thirty Ccf (Clf1p complex factor) proteins have
      been identified by mass spectroscopy or immune detection as known or suspected
      components of the yeast spliceosome. Deletion of TPR1 or TPR2 from an epitope
      tagged Clf1p protein (i.e. Clf1Delta2-TAP) destabilizes Clf1p complexes assembled
      in vivo, causing the release of the Cef1p and Prp19p NTC factors and decreased
      association of the Rse1p, Snu114p, and Hsh155p snRNP proteins. In vitro,
      temperature inactivation of Clf1Delta2p impairs the prespliceosome to spliceosome
      transition and prevents Prp19p recruitment to the splicing complex. These and
      related data support the view that the poly-TPR Clf1p splicing factor promotes
      the functional integration of the U4/U6.U5 tri-snRNP particle into the U1-, U2
      dependent prespliceosome.

PMID- 12509418
TI  - Topoisomerase III can serve as the cellular decatenase in Escherichia coli.
AB  - topB, encoding topoisomerase III, was identified as a high copy suppressor of the
      temperature-sensitive parC1215 allele, encoding one of the subunits of
      topoisomerase IV. Overexpression of topoisomerase III at the nonpermissive
      temperature was shown subsequently to restore timely chromosome decatenation and
      suppress lethality in strains carrying either temperature-sensitive parE or parC
      alleles. By developing an assay in vitro for precatenane unlinking, we
      demonstrated directly that both topoisomerase III and topoisomerase IV were
      efficient at this task, whereas DNA gyrase was very inefficient at precatenane
      removal. These observations suggest that precatenane unlinking is sufficient to
      sustain decatenation of replicating daughter chromosomes in the cell.

PMID- 12509419
TI  - Domain structure characterization of the multifunctional alpha-aminoadipate
      reductase from Penicillium chrysogenum by limited proteolysis. Activation of
      alpha-aminoadipate does not require the peptidyl carrier protein box or the
      reduction domain.
AB  - The alpha-aminoadipate reductase (alpha-AAR) of Penicillium chrysogenum, an
      enzyme that activates the alpha-aminoadipic acid by forming an alpha-aminoadipyl
      adenylate and reduces the activated intermediate to alpha-aminoadipic
      semialdehyde, was purified to homogeneity by immunoaffinity techniques, and the
      kinetics for alpha-aminoadipic acid, ATP, and NADPH were determined. Sequencing
      of the N-terminal end confirmed the 10 first amino acids deduced from the
      nucleotide sequence. Its domain structure has been investigated using limited
      proteolysis and active site labeling. Trypsin and elastase were used to cleave
      the multienzyme, and the location of fragments within the primary structure was
      established by N-terminal sequence analysis. Initial proteolysis generated two
      fragments: an N-terminal fragment housing the adenylation and the peptidyl
      carrier protein (PCP) domains (116 kDa) and a second fragment containing most of
      the reductive domain (28 kDa). Under harsher conditions the adenylation domain
      (about 64 kDa) and the PCP domain (30 kDa) become separated. Time-dependent
      acylation of alpha-AAR and of fragments containing the adenylation domain with
      tritiated alpha-aminoadipate occurred in vitro in the absence of NADPH. Addition
      of NADPH to the labeled alpha-AAR released most of the radioactive substrate. A
      fragment containing the adenylation domain was labeled even in absence of the PCP
      box. The labeling of this fragment (lacking PCP) was always weaker than that
      observed in the di-domain (adenylating and PCP) fragment suggesting that the PCP
      domain plays a role in the stability of the acyl intermediate. Low intensity
      direct acylation of the PCP box has also been observed. A domain structure of
      this multienzyme is proposed.

PMID- 12509420
TI  - Role of proapoptotic BAX in propagation of Chlamydia muridarum (the mouse
      pneumonitis strain of Chlamydia trachomatis) and the host inflammatory response.
AB  - The BCL-2 family member BAX plays a critical role in regulating apoptosis.
      Surprisingly, bax-deficient mice display limited phenotypic abnormalities. Here
      we investigate the effect of BAX on infection by the sexually transmitted
      pathogen, Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia
      trachomatis). Bax(-/-) cells are relatively resistant to Chlamydia-induced
      apoptosis, and fewer bacteria are recovered after two infection cycles from Bax(
      /-) cells than from wild-type cells. These results suggest that BAX-dependent
      apoptosis may be used to initiate a new round of infection, most likely by
      releasing Chlamydia-containing apoptotic bodies from infected cells that could be
      internalized by neighboring uninfected cells. Nonetheless, infected Bax(-/-)
      cells die through necrosis, which is normally associated with inflammation, more
      often than infected wild-type cells. These studies were confirmed in mice
      infected intravaginally with C. muridarum; since the infection disappears more
      quickly from Bax(-/-) mice than from wild-type mice, secretion of proinflammatory
      cytokines is increased in Bax(-/-) mice, and large granulomas are present in the
      genital tract of Bax(-/-) mice. Taken together, these data suggest that chlamydia
      induced apoptosis via BAX contributes to bacterial propagation and decreases
      inflammation. Bax deficiency results in lower infection and an increased
      inflammatory cytokine response associated with more severe pathology.

PMID- 12509421
TI  - Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis
      in mice lacking both low density lipoprotein receptor-related protein 5 and
      apolipoprotein E.
AB  - LDL receptor-related protein 5 (LRP5) plays multiple roles, including embryonic
      development and bone accrual development. Recently, we demonstrated that LRP5 is
      also required for normal cholesterol metabolism and glucose-induced insulin
      secretion. To further define the role of LRP5 in the lipoprotein metabolism, we
      compared plasma lipoproteins in mice lacking LRP5, apolipoprotein E (apoE), or
      both (apoE;LRP5 double knockout). On a normal chow diet, the apoE;LRP5 double
      knockout mice (older than 4 months of age) had approximately 60% higher plasma
      cholesterol levels compared with the age-matched apoE knockout mice. In contrast,
      LRP5 deficiency alone had no significant effects on the plasma cholesterol
      levels. High performance liquid chromatography analysis of plasma lipoproteins
      revealed that cholesterol levels in the very low density lipoprotein and low
      density lipoprotein fractions were markedly increased in the apoE;LRP5 double
      knockout mice. There were no apparent differences in the pattern of apoproteins
      between the apoE knockout mice and the apoE;LRP5 double knockout mice. The plasma
      clearance of intragastrically loaded triglyceride was markedly impaired by LRP5
      deficiency. The atherosclerotic lesions of the apoE;LRP5 double knockout mice
      aged 6 months were approximately 3-fold greater than those in the age-matched
      apoE-knockout mice. Furthermore, histological examination revealed highly
      advanced atherosclerosis, with remarkable accumulation of foam cells and
      destruction of the internal elastic lamina in the apoE;LRP5 double knockout mice.
      These data suggest that LRP5 mediates both apoE-dependent and apoE-independent
      catabolism of plasma lipoproteins.

PMID- 12509422
TI  - Loss of OPA1 perturbates the mitochondrial inner membrane structure and
      integrity, leading to cytochrome c release and apoptosis.
AB  - OPA1 encodes a large GTPase related to dynamins, anchored to the mitochondrial
      cristae inner membrane, facing the intermembrane space. OPA1 haplo-insufficiency
      is responsible for the most common form of autosomal dominant optic atrophy
      (ADOA, MIM165500), a neuropathy resulting from degeneration of the retinal
      ganglion cells and optic nerve atrophy. Here we show that down-regulation of OPA1
      in HeLa cells using specific small interfering RNA (siRNA) leads to fragmentation
      of the mitochondrial network concomitantly to the dissipation of the
      mitochondrial membrane potential and to a drastic disorganization of the cristae.
      These events are followed by cytochrome c release and caspase-dependent apoptotic
      nuclear events. Similarly, in NIH-OVCAR-3 cells, the OPA1 siRNA induces
      mitochondrial fragmentation and apoptosis, the latter being inhibited by Bcl2
      overexpression. These results suggest that OPA1 is a major organizer of the
      mitochondrial inner membrane from which the maintenance of the cristae integrity
      depends. As loss of OPA1 commits cells to apoptosis without any other stimulus,
      we propose that OPA1 is involved in the cytochrome c sequestration and might be a
      target for mitochondrial apoptotic effectors. Our results also suggest that
      abnormal apoptosis is a possible pathophysiological process leading to the
      retinal ganglion cells degeneration in ADOA patients.

PMID- 12509423
TI  - Protein kinase C mediates translocation of type II phosphatidylinositol 5
      phosphate 4-kinase required for platelet alpha-granule secretion.
AB  - To better understand the molecular mechanisms of platelet granule secretion, we
      have evaluated the role of type II phosphatidylinositol (PtdIns) 5-phosphate 4
      kinase in agonist-induced platelet alpha-granule secretion. SFLLRN-stimulated
      alpha-granule secretion from SL-O-permeabilized platelets was inhibited by either
      antibodies directed at type II PtdIns 5-phosphate 4-kinase or by a kinase
      impaired point mutant of type IIbeta PtdIns 5-phosphate 4-kinase. In contrast,
      recombinant type IIbeta PtdIns 5-phosphate 4-kinase augmented SFLLRN-stimulated
      alpha-granule secretion from SL-O-permeabilized platelets. SFLLRN-stimulated
      alpha-granule secretion was inhibited by a protein kinase C-specific inhibitor
      peptide or bisindolylmaleimide I. Phorbol 12-myristate 13-acetate-stimulated
      alpha-granule secretion was inhibited by anti-type II PtdIns 5-phosphate 4-kinase
      antibodies or the kinase-impaired point mutant of type IIbeta PtdIns 5-phosphate
      4-kinase and augmented by recombinant type IIbeta PtdIns 5-phosphate 4-kinase.
      Immunoblot analysis demonstrated that type II PtdIns 5-phosphate 4-kinase
      remained associated with SL-O-permeabilized platelets when incubated in the
      presence, but not the absence, of SFLLRN. This SFLLRN-induced translocation of
      type II PtdIns 5-phosphate 4-kinase was blocked by either the protein kinase C
      specific inhibitor peptide or bisindolylmaleimide I. In addition to stimulating
      alpha-granule secretion, both SFLLRN and PMA enhanced the association of a
      fluorescein isothiocyanate-labeled peptide derived from the PtdIns (4,5)P(2)
      binding domain of gelsolin to permeabilized platelets. Agonist-induced
      recruitment of the PtdIns (4,5)P(2)-binding domain was inhibited by neomycin,
      bisindolylmaleimide I, and anti-type II PtdIns 5-phosphate 4-kinase antibody.
      These results suggest a mechanism whereby protein kinase C-mediated translocation
      of type II PtdIns 5-phosphate 4-kinase leads to the recruitment of PtdIns
      (4,5)P(2)-binding proteins.

PMID- 12509424
TI  - Splicing of a myosin phosphatase targeting subunit 1 alternative exon is
      regulated by intronic cis-elements and a novel bipartite exonic enhancer/silencer
      element.
AB  - Isoforms of the smooth muscle myosin phosphatase targeting subunit 1 (MYPT1) are
      generated by cassette-type alternative splicing of exons. Tissue-specific
      expression of these isoforms is thought to determine smooth muscle-relaxant
      properties and unique responses to signaling pathways. We used mini-gene
      deletion/mutation constructs to identify cis regulators of splicing of the
      chicken MYPT1 central alternative exon. Comparisons of alternative exon splicing
      were made between smooth muscle cells of the fast-phasic contractile phenotype
      (gizzard), in which the central alternative exon is skipped, and slow tonic
      contractile phenotype (aorta), in which the alternative exon is included. We
      demonstrate that splicing of the alternative exon requires a cis-enhancer complex
      in the vicinity of the alternative exon 5'-splice site. This complex consists of
      two UCUU motifs in an intronic U-rich sequence (putative PTB (polypyrimidine
      tract binding) or T cell inhibitor of apoptosis-1 binding sites), an intronic 67
      nucleotide enhancer that has similarities with the cardiac Troponin T MSE3
      enhancer, and a potentially novel exonic splicing enhancer. The exonic enhancer
      contains the palindromic sequence UCCUACAUCCU present in many other transcripts
      where alternative splicing of exons occurs, suggesting that it may be more
      broadly active. The exonic enhancer is adjacent to a potentially novel exonic
      silencer element that contains a 13-nucleotide imperfect palindromic sequence.
      This silencer, in conjunction with a distal intronic silencer, is proposed to
      mediate the silencing of splicing of the MYPT1 central alternative exon in the
      fast phasic smooth muscle phenotype.

PMID- 12509425
TI  - Interaction of NF-E2 in the human beta-globin locus control region before
      chromatin remodeling.
AB  - When transcription is initiated under repressive conditions, such as when
      chromatin are packed together, binding followed by the functioning of key
      components in the transcriptional apparatus should be appropriately facilitated
      in the chromatin architecture. We provide evidence that the erythroid-specific
      enhancer- binding protein NF-E2 interacts with the cognate motif at DNase I
      hypersensitive site 2 of the human beta-globin locus control region in a
      repressive state. The nucleosome containing the NF-E2-binding site showed
      characteristic rotational and translational phases in vitro. The binding site had
      less affinity to the histone octamers than nearby regions while showing greater
      accessibility to DNase I and micrococcal nuclease. Furthermore, the motif was
      recognized by the exogenous NF-E2 protein expressed in HeLa cells, which have a
      repressive state of chromatin at the beta-globin locus, as shown by ligation
      mediated PCR and chromatin immunoprecipitation assay. These lines of evidence
      indicate that NF-E2 interacts with the cognate motif on the nucleosome before
      chromatin is remodeled.

PMID- 12509426
TI  - Oxidative stress regulates vascular endothelial growth factor-A gene
      transcription through Sp1- and Sp3-dependent activation of two proximal GC-rich
      promoter elements.
AB  - Enhanced VEGF-A (vascular endothelial growth factor A) gene expression is
      associated with increased tumor growth and metastatic spread of solid
      malignancies including gastric cancer. Oxidative stress has been linked to tumor
      associated neoangiogenesis; underlying mechanisms, however, remained poorly
      understood. Therefore, we studied the effect of oxidative stress on VEGF-A gene
      expression in gastric cancer cells. Oxidative stress generated by H(2)O(2)
      application potently stimulated VEGF-A protein and mRNA levels as determined by
      enzyme-linked immunosorbent assay and real-time PCR techniques, respectively, and
      elevated the activity of a transfected (-2018) VEGF-A promoter reporter gene
      construct in a time- and dose-dependent manner (4-8-fold). These effects were
      abolished by the antioxidant N-acetylcysteine, demonstrating specificity of
      oxidative stress responses. Functional 5' deletion analysis mapped the oxidative
      stress response element of the human VEGF-A promoter to the sequence -88/-50, and
      a single copy of this element was sufficient to confer basal promoter activity as
      well as oxidative stress responsiveness to a heterologous promoter system.
      Combination of EMSA studies, Sp1/Sp3 overexpression experiments in Drosophila SL
      2 cells, and systematic promoter mutagenesis identified enhanced Sp1 and Sp3
      binding to two GC-boxes at -73/-66 and -58/-52 as the core mechanism of oxidative
      stress-triggered VEGF-A transactivation. Additionally, in Gal4-Sp1/-Sp3-Gal4
      luciferase assays, oxidative stress increased Sp1 but not Sp3 transactivating
      capacity, indicating additional mechanism(s) of VEGF-A gene regulation. Signaling
      studies identified a cascade comprising Ras --> Raf --> MEK1 --> ERK1/2 as the
      main pathway mediating oxidative stress-stimulated VEGF-A transcription. This
      study for the first time delineates the mechanisms underlying regulation of VEGF
      A gene transcription by oxidative stress and thereby further elucidates potential
      pathways underlying redox control of neoangiogenesis.

PMID- 12509427
TI  - Rac2 regulation of phospholipase C-beta 2 activity and mode of membrane
      interactions in intact cells.
AB  - Phospholipase C-beta (PLCbeta) isozymes play important roles in transmembrane
      signaling. Their activity is regulated by heterotrimeric G proteins. The
      PLCbeta(2) isozyme is unique in being stimulated also by Rho GTPases (Rac and
      Cdc42). However, the mechanism(s) of this stimulation are still unclear. Here, we
      employed fluorescence recovery after photobleaching to investigate the
      interaction of green fluorescent protein (GFP)-PLCbeta(2) with the plasma
      membrane. For either GFP-PLCbeta(2) or GFP-PLCbeta(2)Delta, a C-terminal deletion
      mutant lacking the region required for stimulation by Galpha(q), these
      interactions were characterized by a mixture of exchange with a cytoplasmic pool
      and lateral diffusion. Constitutively active Rac2(12V) stimulated the activity of
      both GFP-PLCbeta(2) and GFP-PLCbeta(2)Delta in live cells, and enhanced their
      membrane association as evidenced by the marked reduction in their fluorescence
      recovery rates. Both effects required the putative N-terminal pleckstrin homology
      (PH) domain of PLCbeta(2). Importantly, Rac2(12V) dramatically increased the
      contribution of exchange to the fluorescence recovery of GFP-PLCbeta(2), but had
      the opposite effect on GFP-PLCbeta(2)Delta, where lateral diffusion became
      dominant. Our results demonstrate for the first time the regulation of membrane
      association of a PLCbeta isozyme by a GTP-binding protein and assign a novel
      function to the PLCbeta(2) C-terminal region, regulating its exchange between
      membrane-bound and cytosolic states.

PMID- 12509428
TI  - Nitric oxide, NOC-12, and S-nitrosoglutathione modulate the skeletal muscle
      calcium release channel/ryanodine receptor by different mechanisms. An allosteric
      function for O2 in S-nitrosylation of the channel.
AB  - The skeletal muscle Ca(2+) release channel/ryanodine receptor (RyR1) contains
      approximately 50 thiols per subunit. These thiols have been grouped according to
      their reactivity/responsiveness toward NO, O(2), and glutathione, but the
      molecular mechanism enabling redox active molecules to modulate channel activity
      is poorly understood. In the case of NO, very low concentrations (submicromolar)
      activate RyR1 by S-nitrosylation of a single cysteine residue (Cys-3635), which
      resides within a calmodulin binding domain. S-Nitrosylation of Cys-3635 only
      takes place at physiological tissue O(2) tension (pO(2); i.e. approximately 10 mm
      Hg) but not at pO(2) approximately 150 mm Hg. Two explanations have been offered
      for the loss of RyR1 responsiveness to NO at ambient pO(2), i.e. Cys-3635 is
      oxidized by O(2) versus O(2) subserves an allosteric function (Eu, J. P., Sun, J.
      H., Xu, L., Stamler, J. S., and Meissner, G. (2000) Cell 102, 499-509). Here we
      report that the NO donors NOC-12 and S-nitrosoglutathione both activate RyR1 by
      release of NO but do so independently of pO(2). Moreover, NOC-12 activates the
      channel by S-nitrosylation of Cys-3635 and thereby reverses channel inhibition by
      calmodulin. In contrast, S-nitrosoglutathione activates RyR1 by oxidation and S
      nitrosylation of thiols other than Cys-3635 (and calmodulin is not involved). Our
      results suggest that the effect of pO(2) on RyR1 S-nitrosylation is exerted
      through an allosteric mechanism.

PMID- 12509429
TI  - Mutagenesis of prochlorothrix plastocyanin reveals additional features in
      photosystem I interactions.
AB  - Three surface residues of plastocyanin from Prochlorothrix hollandica have been
      modified by site-directed mutagenesis. Changes have been made in methionine 33,
      located in the hydrophobic patch of the copper protein, and in arginine 86 and
      proline 53, both located in the eastern hydrophilic area. The reactivity toward
      photosystem I of single mutants M33N, P53A, P53E, R86Q, R86E, and the double
      mutant M33N/P14L has been studied by laser flash absorption spectroscopy. All the
      mutations yield increased reactivity of plastocyanin toward photosystem I as
      compared with wild type plastocyanin, thus indicating that in Prochlorothrix
      electron donation to photosystem I is not optimized. The most drastic increases
      in the intracomplex electron transfer rate are obtained with mutants in
      methionine 33, whereas replacing arginine 86 only modestly affects the
      plastocyanin-photosystem I equilibrium constant for complex formation. Mutations
      at position 53 also promote major changes in the association of plastocyanin with
      photosystem I, yielding a change from a mechanism involving complex formation to
      a simpler collisional interaction. Molecular dynamics calculations indicate that
      mutations at position 33 promote changes in the H-bond network around the copper
      center. The comparative kinetic analysis of the reactivity of Prochlorothrix
      plastocyanin mutants toward photosystem I from other cyanobacteria reveals that
      mutations M33N, P53A, and P53E result in enhanced general reactivity.

PMID- 12509430
TI  - Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine
      nucleotide exchange factor.
AB  - The activation of heterotrimeric G proteins is accomplished primarily by the
      guanine nucleotide exchange activity of ligand-bound G protein-coupled receptors.
      The existence of nonreceptor guanine nucleotide exchange factors for G proteins
      has also been postulated. Yeast two-hybrid screens with Galpha(o) and Galpha(s)
      as baits were performed to identify binding partners of these proteins. Two
      mammalian homologs of the Caenorhabditis elegans protein Ric-8 were identified in
      these screens: Ric-8A (Ric-8/synembryn) and Ric-8B. Purification and biochemical
      characterization of recombinant Ric-8A revealed that it is a potent guanine
      nucleotide exchange factor for a subset of Galpha proteins including Galpha(q),
      Galpha(i1), and Galpha(o), but not Galpha(s). The mechanism of Ric-8A-mediated
      guanine nucleotide exchange was elucidated. Ric-8A interacts with GDP-bound
      Galpha proteins, stimulates release of GDP, and forms a stable nucleotide-free
      transition state complex with the Galpha protein; this complex dissociates upon
      binding of GTP to Galpha.

PMID- 12509431
TI  - Orientation of 1,3-bisphosphoglycerate analogs bound to phosphoglycerate kinase.
AB  - We have previously reported dissociation constants for a range of bisphosphonate
      analogs of 1,3-bisphospho-D-glyceric acid binding to yeast phosphoglycerate
      kinase. Data for the unsymmetrical analogs were difficult to interpret because it
      was not clear in which of the two possible orientations these ligands bound. Here
      we report a novel NMR method for quantifying orientation preference based on
      relaxation effects induced by titration with CrADP, which is applied to these
      ligands. It is shown that all ligands can bind in both orientations but that the
      driving force for the orientational preference is to put the alpha,alpha
      difluoromethanephosphonate group in the "basic patch" (nontransferable phosphate)
      position. The relevance to the design of phosphoglycerate kinase inhibitors is
      discussed.

PMID- 12509432
TI  - Mutational analysis and molecular modeling of the allosteric binding site of a
      novel, selective, noncompetitive antagonist of the metabotropic glutamate 1
      receptor.
AB  - A model of the rmGlu1 seven-transmembrane domain complexed with a negative
      allosteric modulator, 1-ethyl-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-benzo[d]azepin
      3-yl)- 1,6-dihydro-pyrimidine-5-carbonitrile (EM-TBPC) was constructed. Although
      the mGlu receptors belong to the family 3 G-protein-coupled receptors with a low
      primary sequence similarity to rhodopsin-like receptors, the high resolution
      crystal structure of rhodopsin was successfully applied as a template in this
      model and used to select residues for site-directed mutagenesis. Three mutations,
      F801(6.51)A, Y805(6.55)A, and T815(7.39)M caused complete loss of the [(3)H]EM
      TBPC binding and blocked the EM-TBPC-mediated inhibition of glutamate-evoked G
      protein-coupled inwardly rectifying K(+) channel current and [Ca(2+)](i)
      response. The mutation W798(6.48)F increased the binding affinity of antagonist
      by 10-fold and also resulted in a marked decrease in the IC(50) value (4 versus
      128 nm) compared with wild type. The V757(5.47)L mutation led to a dramatic
      reduction in binding affinity by 13-fold and a large increase in the IC(50) value
      (1160 versus 128 nm). Two mutations, N7474(5.51)A and N7504(5.54)A, increased the
      efficacy of the EM-TBPC block of the glutamate-evoked [Ca(2+)](i) response. We
      observed a striking conservation in the position of critical residues. The
      residues Val-757(5.47), Trp-798(6.48), Phe-801(6.51), Tyr-805(6.55), and Thr
      815(7.39) are critical determinants of the EM-TBPC-binding pocket of the mGlu1
      receptor, validating the rhodopsin crystal structure as a template for the family
      3 G-protein-coupled receptors. In our model, the aromatic ring of EM-TBPC might
      interact with the cluster of aromatic residues formed from Trp-798(6.48), Phe
      801(6.51), and Tyr-805(6.55), thereby blocking the movement of the TM6 helix,
      which is crucial for receptor activation.

PMID- 12509433
TI  - Leucine zipper domain targets cAMP-dependent protein kinase to mammalian BK
      channels.
AB  - Large conductance, calcium- and voltage-activated potassium (BK) channels control
      excitability in many tissues and are regulated by several protein kinases and
      phosphatases that remain associated with the channels in cell-free patches of
      membrane. Here, we report the identification of a highly conserved, non
      canonical, leucine zipper (LZ1) in the C terminus of mammalian BK channels that
      is required for cAMP-dependent protein kinase (PKA) to associate with the channel
      and regulate its activity. A synthetic polypeptide encompassing the central d
      position leucine residues in LZ1 blocks the regulation of recombinant mouse BK
      channels by endogenous PKA in HEK293 cells. In contrast, neither an alanine
      substituted LZ1 peptide nor a peptide corresponding to another, more C-terminal
      putative leucine zipper, LZ2, had any effect on regulation of the channels by
      endogenous PKA. Mutagenesis of the central two LZ1 d position leucines to alanine
      in the BK channel also eliminated regulation by endogenous PKA in HEK293 cells
      without altering the channel sensitivity to activation by voltage or by exogenous
      purified PKA. Inclusion of the STREX splice insert in the BK channel protein,
      which switches channel regulation by PKA from stimulation to inhibition, did not
      alter the requirement for an intact LZ1. Although PKA does not bind directly to
      the channel protein in vitro, mutation of LZ1 abolished co-immunoprecipitation of
      PKA and the respective BK channel splice variant from HEK293 cells. Furthermore,
      a 127-amino acid fusion protein encompassing the functional LZ1 domain co
      immunoprecipitates a PKA-signaling complex from rat brain. Thus LZ1 is required
      for the association and regulation of mammalian BK channels by PKA, and other
      putative leucine zippers in the BK channel protein may provide anchoring for
      other regulatory enzyme complexes.

PMID- 12509434
TI  - Folding and insertion of the outer membrane protein OmpA is assisted by the
      chaperone Skp and by lipopolysaccharide.
AB  - We have studied the folding pathway of a beta-barrel membrane protein using outer
      membrane protein A (OmpA) of Escherichia coli as an example. The deletion of the
      gene of periplasmic Skp impairs the assembly of outer membrane proteins of
      bacteria. We investigated how Skp facilitates the insertion and folding of
      completely unfolded OmpA into phospholipid membranes and which are the
      biochemical and biophysical requirements of a possible Skp-assisted folding
      pathway. In refolding experiments, Skp alone was not sufficient to facilitate
      membrane insertion and folding of OmpA. In addition, lipopolysaccharide (LPS) was
      required. OmpA remained unfolded when bound to Skp and LPS in solution. From this
      complex, OmpA folded spontaneously into lipid bilayers as determined by
      electrophoretic mobility measurements, fluorescence spectroscopy, and circular
      dichroism spectroscopy. The folding of OmpA into lipid bilayers was inhibited
      when one of the periplasmic components, either Skp or LPS, was absent. Membrane
      insertion and folding of OmpA was most efficient at specific molar ratios of
      OmpA, Skp, and LPS. Unfolded OmpA in complex with Skp and LPS folded faster into
      phospholipid bilayers than urea-unfolded OmpA. Together, these results describe a
      first assisted folding pathway of an integral membrane protein on the example of
      OmpA.

PMID- 12509435
TI  - Overexpression of the Linker histone-binding protein tNASP affects progression
      through the cell cycle.
AB  - NASP is an H1 histone-binding protein that is cell cycle-regulated and occurs in
      two major forms: tNASP, found in gametes, embryonic cells, and transformed cells;
      and sNASP, found in all rapidly dividing somatic cells (Richardson, R. T.,
      Batova, I. N., Widgren, E. E., Zheng, L. X., Whitfield, M., Marzluff, W. F., and
      O'Rand, M. G. (2000) J. Biol. Chem. 275, 30378-30386). When full-length tNASP
      fused to green fluorescent protein (GFP) is transiently transfected into HeLa
      cells, it is efficiently transported into the nucleus within 2 h after
      translation in the cytoplasm, whereas the NASP nuclear localization signal (NLS)
      deletion mutant (NASP-DeltaNLS-GFP) is retained in the cytoplasm. In HeLa cells
      synchronized by a double thymidine block and transiently transfected to
      overexpress full-length tNASP or NASP-DeltaNLS, progression through the G(1)/S
      border is delayed. Cells transiently transfected to overexpress the histone
      binding site (HBS) deletion mutant (NASP-DeltaHBS) or sNASP were not delayed in
      progression through the G(1)/S border. By using a DNA supercoiling assay, in
      vitro binding data demonstrate that H1 histone-tNASP complexes can transfer H1
      histones to DNA, whereas NASP-DeltaHBS cannot. Measurement of NASP mobility in
      the nucleus by fluorescence recovery after photobleaching indicates that NASP
      mobility is virtually identical to that reported for H1 histones. These data
      suggest that NASP-H1 complexes exist in the nucleus and that tNASP can influence
      cell cycle progression through the G(1)/S border through mediation of DNA-H1
      histone binding.

PMID- 12509436
TI  - Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B
      polymerase. Crystal structures and mechanism of inhibition.
AB  - X-ray crystal structures of two non-nucleoside analogue inhibitors bound to
      hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined to 2.0
      and 2.9 A resolution. These noncompetitive inhibitors bind to the same site on
      the protein, approximately 35 A from the active site. The common features of
      binding include a large hydrophobic region and two hydrogen bonds between both
      oxygen atoms of a carboxylate group on the inhibitor and two main chain amide
      nitrogen atoms of Ser(476) and Tyr(477) on NS5B. The inhibitor-binding site lies
      at the base of the thumb domain, near its interface with the C-terminal extension
      of NS5B. The location of this inhibitor-binding site suggests that the binding of
      these inhibitors interferes with a conformational change essential for the
      activity of the polymerase.

PMID- 12509437
TI  - Interleukin-6/glycoprotein 130-dependent pathways are protective during liver
      regeneration.
AB  - After tissue loss the liver has the unique capacity to restore its mass by
      hepatocyte proliferation. Interleukin-6 (IL6)-deficient mice show a lack in DNA
      synthesis after partial hepatectomy (PH). To define better the role of IL6 and
      its family members for liver regeneration after PH, we used conditional knockout
      mice for glycoprotein 130 (gp130), the common signal transducer of all IL6 family
      members. We show that gp130-dependent pathways control Stat3 activation after PH.
      By using gene array analysis, we demonstrate that c-jun, NF-kappa B, c-myc, and
      tumor necrosis factor receptor expression is gp130-dependent. However, in gp130
      deleted mice only minor effects on cell cycle and on the maximum of DNA synthesis
      after PH were found compared with controls. As in conditional gp130 animals, the
      acute phase response was completely abolished, we considered that other means are
      essential to define the role of gp130-dependent pathways for liver regeneration.
      LPS stimulation in gp130-deleted and also IL6 -/- animals after PH leads to a
      significant reduction in survival and DNA synthesis, which was associated with
      decreased Bcl-xL expression and higher apoptosis in the liver. These results
      indicate that the phenotype concerning the reduction in DNA synthesis might be
      linked to the degree of infection after PH. Thus our results suggest that the
      role of gp130-dependent signaling is not a direct influence on cell cycle
      progression after partial hepatectomy but is to activate protective pathways
      important to enable hepatocyte proliferation.

PMID- 12509438
TI  - Insight into the mechanism of dopamine D1-like receptor activation. Evidence for
      a molecular interplay between the third extracellular loop and the cytoplasmic
      tail.
AB  - A chimeric D1A dopaminergic receptor harboring the cytoplasmic tail (CT) of the
      D1B subtype (D1A-CTB) has been used previously to show that CT imparts high
      dopamine (DA) affinity and constitutive activity to the D1B receptors. However,
      the D1A-CTB chimera, unlike the D1B subtype, exhibits a significantly lower DA
      potency for stimulating adenylyl cyclase and a drastically lower maximal binding
      capacity (Bmax). Here, using a functional complementation of chimeric D1-like
      receptors, we have identified the human D1B receptor regions regulating the
      intramolecular relationships that lead to an increased DA potency and contribute
      to Bmax. We demonstrate that the addition of variant residues of the third
      extracellular loop (EL3) of the human D1B receptor into D1A-CTB chimera leads to
      a constitutively active mutant receptor displaying an increased DA affinity,
      potency, and Bmax. These results strongly suggest that constitutively active D1
      like receptors can adopt multiple active conformations, notably one that confers
      increased DA affinity with decreased DA potency and Bmax and another that imparts
      increased DA affinity with a strikingly increased DA potency and Bmax. Overall,
      we show that a novel molecular interplay between EL3 and CT regulates multiple
      active conformations of D1-like receptors and may have potential implications for
      other G protein-coupled receptor classes.

PMID- 12509439
TI  - Stimulation of phosphatidylserine biosynthesis and facilitation of UV-induced
      apoptosis in Chinese hamster ovary cells overexpressing phospholipid scramblase
      1.
AB  - Members of the phospholipid scramblase (PLSCR) family play active roles in
      altering lipid asymmetry at the plasma membrane including phosphatidylserine
      (PtdSer) exposure on the cell surface. To determine whether PtdSer biosynthesis
      and externalization are altered by PLSCR activities during apoptosis, Chinese
      hamster ovary K1 cell lines stably overexpressing PLSCR1 and PLSCR2 were
      established. PLSCR1 was localized on the plasma membrane, whereas PLSCR2 was
      predominantly in the nucleus. Cells overexpressing PLSCR1 showed suppressed
      growth, altered cell morphology, and higher basal levels of cell death. Following
      UV irradiation, these cells showed earlier and enhanced PtdSer exposure,
      increased caspase-3 activation, apoptotic nuclear changes, and PARP cleavage
      indicative of apoptosis. UV irradiation in cells overexpressing PLSCR1 led to a 4
      fold stimulation of PtdSer synthesis (accompanied by increased movement of newly
      made PtdSer into microvesicles) relative to untreated PLSCR1 cells, whereas
      PtdSer formation in UV-irradiated vector control cells increased only by 2-fold.
      No differences in these responses were observed between PLSCR2-expressing cells
      and vector controls. PtdSer synthesis and its transbilayer movement stimulated by
      PLSCR1 overexpression were blocked by a caspase inhibitor along with progression
      of apoptosis. Thus, our studies showed that overexpression of PLSCR1 in Chinese
      hamster ovary K1 cells stimulated caspase-dependent PtdSer externalization and
      synthesis, implying an up-regulation of PtdSer formation in response to enhanced
      outward movement of this phospholipid to the cell surface during apoptosis.
      PLSCR1 also appears to influence progression of UV-induced apoptosis and could be
      a point of regulation or intervention during programmed cell death.

PMID- 12509440
TI  - Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine
      phosphorylation of a kinase-anchoring protein 3 and valosin-containing
      protein/p97 during capacitation.
AB  - Before fertilization can occur, mammalian sperm must undergo capacitation, a
      process that requires a cyclic AMP-dependent increase in tyrosine
      phosphorylation. To identify proteins phosphorylated during capacitation, two
      dimensional gel analysis coupled to anti-phosphotyrosine immunoblots and tandem
      mass spectrometry (MS/MS) was performed. Among the protein targets, valosin
      containing protein (VCP), a homolog of the SNARE-interacting protein NSF, and two
      members of the A kinase-anchoring protein (AKAP) family were found to be tyrosine
      phosphorylated during capacitation. In addition, immobilized metal affinity
      chromatography was used to investigate phosphorylation sites in whole protein
      digests from capacitated human sperm. To increase this chromatographic
      selectivity for phosphopeptides, acidic residues in peptide digests were
      converted to their respective methyl esters before affinity chromatography. More
      than 60 phosphorylated sequences were then mapped by MS/MS, including precise
      sites of tyrosine and serine phosphorylation of the sperm tail proteins AKAP-3
      and AKAP-4. Moreover, differential isotopic labeling was developed to quantify
      phosphorylation changes occurring during capacitation. The phosphopeptide
      enrichment and quantification methodology coupled to MS/MS, described here for
      the first time, can be employed to map and compare phosphorylation sites involved
      in multiple cellular processes. Although we were unable to determine the exact
      site of phosphorylation of VCP, we did confirm, using a cross-immunoprecipitation
      approach, that this protein is tyrosine phosphorylated during capacitation.
      Immunolocalization of VCP showed fluorescent staining in the neck of
      noncapacitated sperm. However, after capacitation, staining in the neck
      decreased, and most of the sperm showed fluorescent staining in the anterior
      head.

PMID- 12509441
TI  - Exportin-5 mediates nuclear export of minihelix-containing RNAs.
AB  - The adenovirus VA1 RNA (VA1), a 160-nucleotide (nt)-long RNA transcribed by RNA
      polymerase III, is efficiently exported from the nucleus to the cytoplasm of
      infected cells, where it antagonizes the interferon-induced antiviral defense
      system. We recently reported that nuclear export of VA1 is mediated by a cis
      acting RNA export motif, called minihelix, that comprises a double-stranded stem
      (>14 nt) with a base-paired 5' end and a 3-8-nt protruding 3' end. RNA export
      mediated by the minihelix motif is Ran-dependent, which indicates the involvement
      of a karyopherin-related factor (exportin) that remained to be determined. Here
      we show using microinjection in Xenopus laevis oocytes that VA1 is transported to
      the cytoplasm by exportin-5, a nuclear transport factor for double-stranded RNA
      binding proteins. Gel retardation assays revealed that exportin-5 directly
      interacts with VA1 RNA in a RanGTP-dependent manner. More generally, in vivo and
      in vitro competition experiments using various VA1-derived, but also artificial
      and cellular, RNAs lead to the conclusion that exportin-5 preferentially
      recognizes and transports minihelix motif-containing RNAs.

PMID- 12509442
TI  - Double-stranded RNA signaling by Toll-like receptor 3 requires specific tyrosine
      residues in its cytoplasmic domain.
AB  - Double-stranded (ds) RNA, a common product of viral infection, can induce
      transcription of many cellular genes, including the 561 gene that encodes P56, a
      regulator of protein synthesis. Here, we report that induction of the 561 mRNA by
      exogenous dsRNA is mediated by Toll-like receptor 3 (TLR3), and it requires no
      new protein synthesis. Because gene induction by dsRNA is blocked by inhibitors
      of tyrosine kinases, we investigated the potential roles of the five tyrosine
      residues present in the cytoplasmic domain of TLR3 by their individual and
      combinatorial mutations. Transfection assays, using a reporter gene driven by the
      561 promoter, identified specific tyrosine residues to be essential for TLR3
      signaling. This conclusion was further validated in permanent cell lines
      expressing tyrosine-mutant TLR3 proteins; in some of these cell lines dsRNA
      failed to induce the 561 mRNA. Our results provide the first demonstration of the
      importance of TLR3 cytoplasmic tyrosine residues in dsRNA signaling.

PMID- 12509443
TI  - p38 Mitogen-activated protein kinase-dependent and -independent signaling of mRNA
      stability of AU-rich element-containing transcripts.
AB  - Adenylate/uridylate-rich element (ARE)-mediated mRNA turnover is an important
      regulatory component of gene expression for innate and specific immunity, in the
      hematopoietic system, in cellular growth regulation, and for many other cellular
      processes. This diversity is reflected in the distribution of AREs in the human
      genome, which we have established as a database of more than 900 ARE-containing
      genes that may utilize AREs as a means of controlling cellular mRNA levels. The
      p38 mitogen-activated protein kinase (MAP kinase) pathway has been implicated in
      regulating the stability of nine ARE-containing transcripts. Here we explored the
      entire spectrum of ARE-containing genes for p38-dependent regulation of ARE
      mediated mRNA turnover with a custom cDNA array containing probes for 950 ARE
      mRNAs. The human monocytic cell line THP-1 treated with lipopolysaccharide (LPS)
      was used as a reproducible cellular model system that allowed us to precisely
      control the conditions of mRNA induction and decay in the absence and presence of
      the p38 inhibitor SB203580. This approach allowed us to establish an LPS-induced
      ARE mRNA expression profile in human monocytes and determine the half-lives of
      470 AU-rich mRNAs. Most importantly, we identified 42 AU-rich genes, previously
      unrecognized, that show p38-dependent mRNA stabilization. In addition to a number
      of cytokines, several interesting novel AU-rich transcripts likely to play a role
      in macrophage activation by LPS exhibited p38-dependent transcript stabilization,
      including macrophage-specific colony-stimulating factor 1, carbonic anhydrase 2,
      Bcl2, Bcl2-like 2, and nuclear factor erythroid 2-like 2. Finally, the
      identification of the p38-dependent upstream activator MAP kinase kinase 6 as a
      member of this group identifies a positive feedback loop regulating macrophage
      signaling via p38 MAP kinase-dependent transcript stabilization.

PMID- 12509445
TI  - Mcm1p-induced DNA bending regulates the formation of ternary transcription factor
      complexes.
AB  - The yeast MADS-box transcription factor Mcm1p plays an important regulatory role
      in several diverse cellular processes. In common with a subset of other MADS-box
      transcription factors, Mcm1p elicits substantial DNA bending. However, the role
      of protein-induced bending by MADS-box proteins in eukaryotic gene regulation is
      not understood. Here, we demonstrate an important role for Mcm1p-mediated DNA
      bending in determining local promoter architecture and permitting the formation
      of ternary transcription factor complexes. We constructed mutant mcm1 alleles
      that are defective in protein-induced bending. Defects in nuclear division, cell
      growth or viability, transcription, and gene expression were observed in these
      mutants. We identified one likely cause of the cell growth defects as the
      aberrant formation of the cell cycle-regulatory Fkh2p-Mcm1p complex. Microarray
      analysis confirmed the importance of Mcm1p-mediated DNA bending in maintaining
      correct gene expression profiles and revealed defects in Mcm1p-mediated
      repression of Ty elements and in the expression of the cell cycle-regulated YFR
      and CHS1 genes. Thus, we discovered an important role for DNA bending by MADS-box
      proteins in the formation and function of eukaryotic transcription factor
      complexes.

PMID- 12509444
TI  - Association between hepatocyte nuclear factor 6 (HNF-6) and FoxA2 DNA binding
      domains stimulates FoxA2 transcriptional activity but inhibits HNF-6 DNA binding.
AB  - In previous studies we used transgenic mice or recombinant adenovirus infection
      to increase hepatic expression of forkhead box A2 (FoxA2, previously called
      hepatocyte nuclear factor 3beta [HNF-3beta]), which caused diminished hepatocyte
      glycogen levels and reduced expression of glucose homeostasis genes. Because this
      diminished expression of FoxA2 target genes was associated with reduced levels of
      the Cut-Homeodomain HNF-6 transcription factor, we conducted the present study to
      determine whether there is a functional interaction between HNF-6 and FoxA2.
      Human hepatoma (HepG2) cotransfection assays demonstrated that HNF-6
      synergistically stimulated FoxA2 but not FoxA1 or FoxA3 transcriptional activity,
      and protein-binding assays showed that this protein interaction required the HNF
      6 Cut-Homeodomain and FoxA2 winged-helix DNA binding domains. Furthermore, we
      show that the HNF-6 Cut-Homeodomain sequences were sufficient to synergistically
      stimulate FoxA2 transcriptional activation by recruiting the p300/CBP coactivator
      proteins. This was supported by the fact that FoxA2 transcriptional synergy with
      HNF-6 was dependent on retention of the HNF-6 Cut domain LXXLL sequence, which
      mediated recruitment of the p300/CBP proteins. Moreover, cotransfection and DNA
      binding assays demonstrated that increased FoxA2 levels caused a decrease in HNF
      6 transcriptional activation of the glucose transporter 2 (Glut-2) promoter by
      interfering with the binding of HNF-6 to its target DNA sequence. These data
      suggest that at a FoxA-specific site, HNF-6 serves as a coactivator protein to
      enhance FoxA2 transcription, whereas at an HNF-6-specific site, FoxA2 represses
      HNF-6 transcription by inhibiting HNF-6 DNA binding activity. This is the first
      reported example of a liver-enriched transcription factor (HNF-6) functioning as
      a coactivator protein to potentiate the transcriptional activity of another liver
      factor, FoxA2.

PMID- 12509446
TI  - mdm2 Is critical for inhibition of p53 during lymphopoiesis and the response to
      ionizing irradiation.
AB  - The function of the p53 tumor suppressor protein must be highly regulated because
      p53 can cause cell death and prevent tumorigenesis. In cultured cells, the
      p90MDM2 protein blocks the transcriptional activation domain of p53 and also
      stimulates the degradation of p53. Here we provide the first conclusive
      demonstration that p90MDM2 constitutively regulates p53 activity in homeostatic
      tissues. Mice with a hypomorphic allele of mdm2 revealed a heretofore unknown
      role for mdm2 in lymphopoiesis and epithelial cell survival. Phenotypic analyses
      revealed that both the transcriptional activation and apoptotic functions of p53
      were increased in these mice. However, the level of p53 protein was not
      coordinately increased, suggesting that p90MDM2 can inhibit the transcriptional
      activation and apoptotic functions of p53 in a manner independent of degradation.
      Cre-mediated deletion of mdm2 caused a greater accumulation of p53, demonstrating
      that p90MDM2 constitutively regulates both the activity and the level of p53 in
      homeostatic tissues. The observation that only a subset of tissues with activated
      p53 underwent apoptosis indicates that factors other than p90(MDM2) determine the
      physiological consequences of p53 activation. Furthermore, reduction of mdm2 in
      vivo resulted in radiosensitivity, highlighting the importance of mdm2 as a
      potential target for adjuvant cancer therapies.

PMID- 12509447
TI  - Enhanced genomic instability and defective postreplication repair in RAD18
      knockout mouse embryonic stem cells.
AB  - In lower eukaryotes, Rad18 plays a crucial role in postreplication repair.
      Previously, we isolated a human homologue of RAD18 (hRAD18) and showed that human
      cells overexpressing hRad18 protein with a mutation in the RING finger motif are
      defective in postreplication repair. Here, we report the construction of RAD18
      knockout mouse embryonic stem cells by gene targeting. These cells had almost the
      same growth rate as wild-type cells and manifested phenotypes similar to those of
      human cells expressing mutant Rad18 protein: hypersensitivity to multiple DNA
      damaging agents and a defect in postreplication repair. Mutation was not induced
      in the knockout cells with any higher frequencies than in wild-type cells, as
      shown by ouabain resistance. In the knockout cells, spontaneous sister chromatid
      exchange (SCE) occurred with twice the frequency observed in normal cells. After
      mild DNA damage, SCE was threefold higher in the knockout cells, while no
      increase was observed in normal cells. Stable transformation efficiencies were
      approximately 20-fold higher in knockout cells, and gene targeting occurred with
      approximately 40-fold-higher frequency than in wild-type cells at the Oct3/4
      locus. These results indicate that dysfunction of Rad18 greatly increases both
      the frequency of homologous as well as illegitimate recombination, and that RAD18
      contributes to maintenance of genomic stability through postreplication repair.

PMID- 12509448
TI  - Alteration of mesodermal cell differentiation by EWS/FLI-1, the oncogene
      implicated in Ewing's sarcoma.
AB  - The chimeric fusion gene EWS/FLI-1 is detected in most cases of Ewing's sarcoma
      (ES), the second most common malignant bone tumor of childhood. Although 80% of
      ES tumors develop in skeletal sites, the remainder can arise in almost any soft
      tissue location. The lineage of the cell developing the EWS/FLI-1 gene fusion has
      not been fully characterized but is generally considered to be of either
      mesenchymal or neural crest origin. To study this oncogene in a conceptually
      relevant target cell, EWS/FLI-1 was introduced into the murine cell line C2C12, a
      myoblast cell line capable of differentiation into muscle, bone, or fat. In this
      cellular context, EWS/FLI-1 profoundly inhibited the myogenic differentiation
      program. The block in C2C12 myogenic differentiation required the nuclear
      localization and DNA-binding functions of EWS/FLI-1 and was mediated by
      transcriptional and posttranscriptional suppression of the myogenic transcription
      factors MyoD and myogenin. Interestingly, C2C12-EWS/FLI-1 cells constitutively
      expressed alkaline phosphatase, a bone lineage marker, and were alkaline
      phosphatase positive by histochemistry but showed no other evidence of bone
      lineage commitment. Consistent with recent findings in human ES tumor cell lines,
      C2C12-EWS/FLI-1 cells constitutively expressed cyclin D1 and demonstrated
      decreased expression of the cell cycle regulator p21(cip1), even under
      differentiation conditions and at confluent density. This C2C12-EWS/FLI-1 cell
      model may assist in the identification of novel differentially expressed genes
      relevant to ES and provide further insight into the cell(s) of origin developing
      ES-associated genetic fusions.

PMID- 12509449
TI  - The 32-kilodalton subunit of replication protein A interacts with menin, the
      product of the MEN1 tumor suppressor gene.
AB  - Menin is a 70-kDa protein encoded by MEN1, the tumor suppressor gene disrupted in
      multiple endocrine neoplasia type 1. In a yeast two-hybrid system based on
      reconstitution of Ras signaling, menin was found to interact with the 32-kDa
      subunit (RPA2) of replication protein A (RPA), a heterotrimeric protein required
      for DNA replication, recombination, and repair. The menin-RPA2 interaction was
      confirmed in a conventional yeast two-hybrid system and by direct interaction
      between purified proteins. Menin-RPA2 binding was inhibited by a number of menin
      missense mutations found in individuals with multiple endocrine neoplasia type 1,
      and the interacting regions were mapped to the N-terminal portion of menin and
      amino acids 43 to 171 of RPA2. This region of RPA2 contains a weak single
      stranded DNA-binding domain, but menin had no detectable effect on RPA-DNA
      binding in vitro. Menin bound preferentially in vitro to free RPA2 rather than
      the RPA heterotrimer or a subcomplex consisting of RPA2 bound to the 14-kDa
      subunit (RPA3). However, the 70-kDa subunit (RPA1) was coprecipitated from HeLa
      cell extracts along with RPA2 by menin-specific antibodies, suggesting that menin
      binds to the RPA heterotrimer or a novel RPA1-RPA2-containing complex in vivo.
      This finding was consistent with the extensive overlap in the nuclear
      localization patterns of endogenous menin, RPA2, and RPA1 observed by
      immunofluorescence.

PMID- 12509450
TI  - Delineation of a novel pathway that regulates CD154 (CD40 ligand) expression.
AB  - The expression of CD154 (CD40 ligand) by activated T lymphocytes plays a central
      role in humoral and cellular immunity. The fundamental importance of this protein
      in mounting an immune response has made it an attractive target for
      immunomodulation. Several studies have demonstrated that CD154 expression is
      regulated at the level of mRNA turnover in a manner distinct from other cytokine
      genes. We have purified, sequenced, and characterized the two major proteins that
      bind the CD154 3' untranslated region (3'UTR) as members of the polypyrimidine
      tract binding protein (PTB) family. One of these proteins is a previously
      unreported alternatively spliced PTB isoform, which we call PTB-T. These proteins
      interact with a polypyrimidine-rich region within the CD154 3'UTR that lacks any
      known cis-acting instability elements. The polypyrimidine-rich region of the
      CD154 3'UTR was both necessary and sufficient to mediate changes in reporter gene
      expression and mRNA accumulation, indicating the presence of a novel cis-acting
      instability element. The presence of a cis-acting instability element in the
      polypyrimidine-rich region was confirmed using a tetracycline-responsive reporter
      gene approach. The function of this cis-acting element appears to be dependent on
      the relative cytoplasmic levels of PTB and PTB-T. Cotransfection of vectors
      encoding PTB-T consistently decreased the CD154 3'UTR-dependent luciferase
      expression. In contrast, transfection of plasmids encoding PTB tended to increase
      CD154 3'UTR-dependent luciferase expression. Thus, the CD154 3'UTR contains a
      novel cis-acting element whose function is determined by the binding of PTB and
      PTB-T. These data identify a specific pathway that regulates CD154 expression
      that can potentially be selectively targeted for the treatment of autoimmune
      disease and allograft rejection.

PMID- 12509451
TI  - Regulation of tumor necrosis factor alpha gene expression by mycobacteria
      involves the assembly of a unique enhanceosome dependent on the coactivator
      proteins CBP/p300.
AB  - Tumor necrosis factor alpha (TNF-alpha) plays an important role in host
      containment of infection by Mycobacterium tuberculosis, one of the leading causes
      of death by an infectious agent globally. Using the pathogenic M. tuberculosis
      strain H37Rv, we present evidence that upon stimulation of monocytic cells by M.
      tuberculosis a unique TNF-alpha enhanceosome is formed, and it is distinct from
      the TNF-alpha enhanceosome that forms in T cells stimulated by antigen engagement
      or virus infection. A distinct set of activators including ATF-2, c-jun, Ets,
      Sp1, Egr-1 and the coactivator proteins CBP/p300 are recruited to the TNF-alpha
      promoter after stimulation with M. tuberculosis. Furthermore, the formation of
      this enhanceosome is dependent on inducer-specific helical phasing relationships
      between transcription factor binding sites. We also show that the transcriptional
      activity of CBP/p300 is potentiated by mycobacterial stimulation of monocytes.
      The identification of TNF-alpha regulatory elements and coactivators involved in
      M. tuberculosis-stimulated gene expression thus provides potential selective
      molecular targets in the modulation of TNF-alpha gene expression in the setting
      of mycobacterial infection.

PMID- 12509452
TI  - Binding dynamics of structural nucleoporins govern nuclear pore complex
      permeability and may mediate channel gating.
AB  - The nuclear pore complex (NPC) is a permeable sieve that can dilate to facilitate
      the bidirectional translocation of a wide size range of receptor-cargo complexes.
      The binding of receptors to FG nucleoporin docking sites triggers channel gating
      by an unknown mechanism. Previously, we used deoxyglucose and chilling treatments
      to implicate Nup170p and Nup188p in the control of NPC sieving in Saccharomyces
      cerevisiae. Here, we report that aliphatic alcohols increase the permeability of
      wild-type and nup170Delta NPCs. In conjunction with increases in permeability,
      aliphatic alcohols, deoxyglucose, and chilling trigger the reversible
      dissociation of several nucleoporins from nup170Delta NPCs. These results are
      consistent with the hypothesis that NPC gating occurs when molecular latches
      composed of FG repeats and structural nucleoporins dissociate.

PMID- 12509453
TI  - The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine
      paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway.
AB  - Sustained activation of the Ras/Raf/MEK/extracellular signal-regulated kinase
      (ERK) pathway can lead to cell cycle arrest in many cell types. We have found,
      with human medullary thyroid cancer (MTC) cells, that activated Ras or c-Raf-1
      can induce growth arrest by producing and secreting an autocrine-paracrine
      factor. This protein was purified from cell culture medium conditioned by Raf
      activated MTC cells and was identified by mass spectrometry as leukemia
      inhibitory factor (LIF). LIF expression upon Raf activation and subsequent
      activation of JAK-STAT3 was also observed in small cell lung carcinoma cells,
      suggesting that this autocrine-paracrine signaling may be a common response to
      Ras/Raf activation. LIF was sufficient to induce growth arrest and
      differentiation of MTC cells. This effect was mediated through the
      gp130/JAK/STAT3 pathway, since anti-gp130 blocking antibody or dominant-negative
      STAT3 blocked the effects of LIF. Thus, LIF expression provides a novel mechanism
      allowing Ras/Raf signaling to activate the JAK-STAT3 pathway. In addition to this
      cell-extrinsic growth inhibitory pathway, we find that the Ras/Raf/MEK/ERK
      pathway induces an intracellular growth inhibitory signal, independent of the
      LIF/JAK/STAT3 pathway. Therefore, activation of the Ras/Raf/MEK/ERK pathway can
      lead to growth arrest and differentiation via at least two different signaling
      pathways. This use of multiple pathways may be important for "fail-safe"
      induction and maintenance of cell cycle arrest.

PMID- 12509454
TI  - p21(CIP1) Controls proliferating cell nuclear antigen level in adult
      cardiomyocytes.
AB  - Cell cycle withdrawal associated with terminal differentiation is responsible for
      the incapability of many organs to regenerate after injury. Here, we employed a
      cell-free system to analyze the molecular mechanisms underlying cell cycle arrest
      in cardiomyocytes. In this assay, incubation of S phase nuclei mixed with
      cytoplasmic extract of S phase cells and adult primary cardiomyocytes results in
      a dramatic reduction of proliferating cell nuclear antigen (PCNA) protein levels.
      This effect was blocked by the proteasome inhibitors MG132 and lactacystin,
      whereas actinomycin D and cycloheximide had no effect. Immunodepletion and
      addback experiments revealed that the effect of cardiomyocyte extract on PCNA
      protein levels is maintained by p21 but not p27. In serum-stimulated
      cardiomyocytes PCNA expression was reconstituted, whereas the protein level of
      p21 but not that of p27 was reduced. Cytoplasmic extract of serum-stimulated
      cardiomyocytes did not influence the PCNA protein level in S phase nuclei.
      Moreover, the hypertrophic effect of serum stimulation was blocked by ectopic
      expression of p21 and the PCNA protein level was found to be upregulated in adult
      cardiomyocytes derived from p21 knockout mice. Our data provide evidence that p21
      regulates the PCNA protein level in adult cardiomyocytes, which has implications
      for cardiomyocyte growth control.

PMID- 12509455
TI  - T-cadherin-mediated cell growth regulation involves G2 phase arrest and requires
      p21(CIP1/WAF1) expression.
AB  - Members of the cadherin family have been implicated as growth regulators in
      multiple tumor types. Based on recent studies from our laboratory implicating T
      cadherin expression in mouse brain tumorigenesis, we examined the role of T
      cadherin in astrocytoma growth regulation. In this report, we show that T
      cadherin expression increased during primary astrocyte physiologic growth arrest
      in response to contact inhibition and serum starvation in vitro, suggesting a
      function for T-cadherin in astrocyte growth regulation. We further demonstrate
      that transient and stable reexpression of T-cadherin in deficient C6 glioma cell
      lines results in growth suppression. In addition, T-cadherin-expressing C6 cell
      lines demonstrated increased homophilic cell aggregation, increased cell
      attachment to fibronectin, and decreased cell motility. Cell cycle flow cytometry
      demonstrated that T-cadherin reexpression resulted in G2 phase arrest, which was
      confirmed by mitotic index analysis. This growth arrest was p53 independent, as T
      cadherin could still mediate growth suppression in p53(-/-) mouse embryonic
      fibroblasts. T-cadherin-expressing C6 cell lines exhibited increased
      p21(CIP1/WAF1), but not p27(Kip1), expression. Lastly, T-cadherin-mediated growth
      arrest was dependent on p21(CIP1/WAF1) expression and was eliminated in
      p21(CIP1/WAF1)-deficient fibroblasts. Collectively, these observations suggest a
      novel mechanism of growth regulation for T-cadherin involving p21(CIP1/WAF1)
      expression and G2 arrest.

PMID- 12509456
TI  - Extracellular matrix enhances heregulin-dependent BRCA1 phosphorylation and
      suppresses BRCA1 expression through its C terminus.
AB  - Germ line mutations in the breast cancer susceptibility gene BRCA1 account for
      the increased risk of early onset of familial breast cancer, whereas
      overexpression of the ErbB family of receptor tyrosine kinases has been linked to
      the development of nonfamilial or sporadic breast cancer. To analyze whether
      there is a link between these two regulatory molecules, we studied the effects of
      ErbB-2 activation by heregulin (HRG) on BRCA1 function. It was previously
      demonstrated that HRG induced the phosphorylation of BRCA1, which was mediated by
      the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Since altered interaction
      between cells and the surrounding extracellular matrix (ECM) is a common feature
      in a variety of tumors and since ECM modulates intracellular signaling, we
      hypothesized that ECM may affect the expression and HRG-dependent phosphorylation
      of BRCA1. Following stimulation by HRG, a strong increase in [(3)H]thymidine
      incorporation was observed in human T47D breast cancer cells seeded on plastic
      (PL). When T47D cells were seeded on laminin (LAM) or Matrigel, HRG induced a
      significantly higher proliferation than it did in cells seeded on PL. T47D cells
      seeded on poly-L-lysine had an abrogated mitogenic response, indicating the
      involvement of integrins in this process. HRG treatment induced a transient
      phosphorylation of BRCA1 that was enhanced in T47D cells grown on LAM. LAM
      enhanced BRCA1 phosphorylation was mediated through alpha(6) integrin upon HRG
      stimulation. Accordingly, T47D cells grown on LAM had the greatest increase in
      ErbB-2 activation, PI3K activity, and phosphorylation of Akt. A similar pattern
      of BRCA1 mRNA expression was observed when T47D cells were seeded on PL, LAM, or
      COL4. There was a significant decrease in the steady state of the BRCA1 mRNA
      level on both the LAM and COL4 matrices compared to that for cells seeded on PL.
      In addition, HRG stimulation caused a significant decrease in BRCA1 mRNA
      expression that was dependent on protein synthesis. Pretreatment with both the
      calpain inhibitor ALLN (N-acetyl-Leu-Leu-norleucinal) and the proteosome
      inhibitor lactacystin inhibited the HRG-induced down-regulation of BRCA1 mRNA
      expression. Likewise, there was a strong decrease in the protein level of BRCA1
      in T47D cells 4 h after treatment with HRG compared to its level in control
      nontreated T47D cells. Pretreatment with the proteosome inhibitors ALLN,
      lactacystin, and PSI [N-benzyloxycarbonyl-Ile-Glu-(O-t-butyl)-Ala-leucinal]
      inhibited also the HRG-induced down-regulation of BRCA1 protein in breast cancer
      cells. Interestingly, BRCA1 mRNA expression in HCC-1937 breast cancer cells,
      which express C-terminally truncated BRCA1, was not affected by either LAM or
      CL4. No phosphorylation of BRCA1 from HCC-1937 cells was observed in response to
      HRG. While Cdk4 phosphorylated wild-type BRCA1 in response to HRG in T47D cells,
      Cdk4 failed to phosphorylate the truncated form of BRCA1 in HCC-1937 cells.
      Furthermore, overexpression of wild-type BRCA1 in HCC-1937 cells resulted in the
      phosphorylation of BRCA1 and decreased BRCA1 expression upon HRG stimulation
      while overexpression of truncated BRCA1 in T47D cells resulted in a lack of BRCA1
      phosphorylation and restoration of BRCA1 expression. These findings suggest that
      ECM enhances HRG-dependent BRCA1 phosphorylation and that ECM and HRG down
      regulate BRCA1 expression in breast cancer cells. Furthermore, ECM suppresses
      BRCA1 expression through the C terminus of BRCA1.

PMID- 12509457
TI  - Plasma membrane CFTR regulates RANTES expression via its C-terminal PDZ
      interacting motif.
AB  - Despite the identification of 1,000 mutations in the cystic fibrosis gene product
      CFTR, there remains discordance between CFTR genotype and lung disease phenotype.
      The study of CFTR, therefore, has expanded beyond its chloride channel activity
      into other possible functions, such as its role as a regulator of gene
      expression. Findings indicate that CFTR plays a role in the expression of RANTES
      in airway epithelia. RANTES is a chemokine that has been implicated in the
      regulation of mucosal immunity and the pathogenesis of airway inflammatory
      diseases. Results demonstrate that CFTR triggers RANTES expression via a
      mechanism that is independent of CFTR's chloride channel activity. Neither
      pharmacological inhibition of CFTR nor activation of alternative chloride
      channels, including hClC-2, modulated RANTES expression. Through the use of CFTR
      disease-associated and truncation mutants, experiments suggest that CFTR-mediated
      transcription factor activation and RANTES expression require (i) insertion of
      CFTR into the plasma membrane and (ii) an intact CFTR C-terminal PDZ-interacting
      domain. Expression of constructs encoding wild-type or dominant-negative forms of
      the PDZ-binding protein EBP50 suggests that EBP50 may be involved in CFTR
      dependent RANTES expression. Together, these data suggest that CFTR modulates
      gene expression in airway epithelial cells while located in a macromolecular
      signaling complex at the plasma membrane.

PMID- 12509458
TI  - The inv(16) fusion protein associates with corepressors via a smooth muscle
      myosin heavy-chain domain.
AB  - Inversion(16) is one of the most frequent chromosomal translocations found in
      acute myeloid leukemia (AML), occurring in over 8% of AML cases. This
      translocation results in a protein product that fuses the first 165 amino acids
      of core binding factor beta to the coiled-coil region of a smooth muscle myosin
      heavy chain (CBFbeta/SMMHC). CBFbeta interacts with AML1 to form a heterodimer
      that binds DNA; this interaction increases the affinity of AML1 for DNA. The
      CBFbeta/SMMHC fusion protein cooperates with AML1 to repress the transcription of
      AML1-regulated genes. We show that CBFbeta/SMMHC contains a repression domain in
      the C-terminal 163 amino acids of the SMMHC region that is required for inv(16)
      mediated transcriptional repression. This minimal repression domain is sufficient
      for the association of CBFbeta/SMMHC with the mSin3A corepressor. In addition,
      the inv(16) fusion protein specifically associates with histone deacetylase 8
      (HDAC8). inv(16)-mediated repression is sensitive to HDAC inhibitors. We propose
      a model whereby the inv(16) fusion protein associates with AML1 to convert AML1
      into a constitutive transcriptional repressor.

PMID- 12509459
TI  - Role of metazoan mediator proteins in interferon-responsive transcription.
AB  - The interferon (IFN)-induced signal transduction and transcription activation
      complex, ISGF3, is assembled from three proteins, STAT1, STAT2, and IRF9. Of
      these components, STAT2 provides a fundamental and essential transcriptional
      activation function for ISGF3. In the present study, we show that ISGF3-mediated
      transcription is dependent on STAT2 interactions with DRIP150, a subunit of the
      multimeric Mediator coactivator complex. Other Mediator subunits, DRIP77 and
      DRIP130, were found either to bind STAT2 without augmenting ISGF3 transcriptional
      activity or to enhance ISGF3 transcription without binding STAT2, but only
      DRIP150 both enhanced IFN-dependent transcription and coimmunoprecipitated with
      STAT2. Endogenous DRIP150 and STAT2 were able to interact in solution, and DNA
      affinity chromatography and chromatin immunoprecipitation assays demonstrated
      that DRIP150 binds to the mature, activated ISGF3-DNA complex and is recruited to
      target gene promoters in an IFN-dependent fashion. IFN-dependent recruitment of
      DRIP130 to an ISGF3 target promoter and SRB10-STAT2 coprecipitation suggest
      indirect association with a multisubunit Mediator complex. The site of STAT2
      interaction was mapped to DRIP150 residues 188 to 566, which are necessary and
      sufficient for interaction with STAT2. Expression of this DRIP150 fragment, but
      not DRIP150 fragments outside the STAT2 interaction region, suppressed ISGF3
      mediated transcriptional activity in a dominant-negative fashion, suggesting a
      direct functional role of this domain in mediating STAT2-DRIP150 interactions.
      These findings indicate that the IFN-activated ISGF3 transcription factor
      regulates transcription through contact with DRIP150 and implicate the Mediator
      coactivator complex in IFN-activated gene regulation.

PMID- 12509460
TI  - The tor pathway regulates gene expression by linking nutrient sensing to histone
      acetylation.
AB  - The Tor pathway mediates cell growth in response to nutrient availability, in
      part by inducing ribosomal protein (RP) gene expression via an unknown mechanism.
      Expression of RP genes coincides with recruitment of the Esa1 histone acetylase
      to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1
      from RP gene promoters and leads to histone H4 deacetylation without affecting
      promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies
      Rpd3 as the major histone deacetylase responsible for reversing histone H4
      acetylation at RP gene promoters in response to Tor inhibition by rapamycin or
      nutrient limitation. Our results illustrate that the Tor pathway links nutrient
      sensing with histone acetylation to control RP gene expression and cell growth.

PMID- 12509461
TI  - Chondromodulin I is a bone remodeling factor.
AB  - Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage
      and its functions in cultured chondrocytes as a major regulator in cartilage
      development. Here, we generated mice deficient in ChM-I by targeted disruption of
      the ChM-I gene. No overt abnormality was detected in endochondral bone formation
      during embryogenesis and cartilage development during growth stages of ChM-I(-/-)
      mice. However, a significant increase in bone mineral density with lowered bone
      resorption with respect to formation was unexpectedly found in adult ChM-I(-/-)
      mice. Thus, the present study established that ChM-I is a bone remodeling factor.

PMID- 12509462
TI  - Elevated phospholipase D activity in H-Ras- but not K-Ras-transformed cells by
      the synergistic action of RalA and ARF6.
AB  - Phospholipase D (PLD) activity is elevated in response to the oncogenic stimulus
      of H-Ras but not K-Ras. H-Ras and K-Ras have been reported to localize to
      different membrane microdomains, with H-Ras localizing to caveolin-enriched light
      membrane fractions. We reported previously that PLD activity elevated in response
      to mitogenic stimulation is restricted to the caveolin-enriched light membrane
      fractions. PLD activity in H-Ras-transformed cells is dependent upon RalA, and
      consistent with a lack of elevated PLD activity in K-Ras-transformed cells, RalA
      was not activated in K-Ras-transformed cells. Although H-Ras-induced PLD activity
      is dependent upon RalA, an activated mutant of RalA is not sufficient to elevate
      PLD activity. We reported previously that RalA interacts with PLD activating ADP
      ribosylation factor (ARF) proteins. In cells transformed by H-Ras, we found
      increased coprecipitation of ARF6 with RalA. Moreover, ARF6 colocalized with RalA
      in light membrane fractions. Interestingly, ARF6 protein levels were elevated in
      H-Ras- but not K-Ras-transformed cells. A dominant-negative mutant of ARF6
      inhibited PLD activity in H-Ras-transformed NIH 3T3 cells. Activated mutants of
      either ARF6 or RalA were not sufficient to elevate PLD activity in NIH 3T3 cells;
      however, expression of both activated RalA and activated ARF6 in NIH 3T3 cells
      led to increased PLD activity. These data suggest a model whereby H-Ras
      stimulates the activation of both RalA and ARF6, which together lead to the
      elevation of PLD activity.

PMID- 12509463
TI  - Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of
      notch signaling.
AB  - Constitutive NOTCH signaling in lymphoid progenitors promotes the development of
      immature T-cell lymphoblastic neoplasms (T-ALLs). Although it is clear that Notch
      signaling can initiate leukemogenesis, it has not previously been established
      whether continued NOTCH signaling is required to maintain T-ALL growth. We
      demonstrate here that the blockade of Notch signaling at two independent steps
      suppresses the growth and survival of NOTCH1-transformed T-ALL cells. First,
      inhibitors of presenilin specifically induce growth suppression and apoptosis of
      a murine T-ALL cell line that requires presenilin-dependent proteolysis of the
      Notch receptor in order for its intracellular domain to translocate to the
      nucleus. Second, a 62-amino-acid peptide derived from a NOTCH coactivator,
      Mastermind-like-1 (MAML1), forms a transcriptionally inert nuclear complex with
      NOTCH1 and CSL and specifically inhibits the growth of both murine and human
      NOTCH1-transformed T-ALLs. These studies show that continued growth and survival
      of NOTCH1-transformed lymphoid cell lines require nuclear access and
      transcriptional coactivator recruitment by NOTCH1 and identify at least two steps
      in the Notch signaling pathway as potential targets for chemotherapeutic
      intervention.

PMID- 12509464
TI  - Susceptibility of lysosomes to rupture is a determinant for plasma membrane
      disruption in tumor necrosis factor alpha-induced cell death.
AB  - Since a release of intracellular contents can induce local inflammatory
      responses, mechanisms that lead to loss of plasma membrane integrity in cell
      death are important to know. We showed previously that deficiency of the plasma
      membrane Ca2+ ATPase 4 (PMCA4) in L929 cells impaired tumor necrosis factor alpha
      (TNF-alpha)-induced enlargement of lysosomes and reduced cell death. The
      lysosomal changes can be determined by measuring the total volume of
      intracellular acidic compartments per cell (VAC), and we show here that
      inhibition of the increase in VAC due to PMCA4 deficiency not only reduced cell
      death but also converted TNF-alpha-induced cell death from a process involving
      disruption of the plasma membrane to a cell demise with a nearly intact plasma
      membrane. The importance of the size of lysosomes in determining plasma membrane
      integrity during cell death was supported by the observations that chemical
      inhibitors that reduce VAC also reduced the plasma membrane disruption induced by
      TNF-alpha in wild-type L929 cells, while increases in VAC due to genetic
      mutation, senescence, cell culture conditions, and chemical inhibitors all
      changed the morphology of cell death from one with an originally nearly intact
      plasma membrane to one with membrane disruption in a number of different cells.
      Moreover, the ATP depletion-mediated change from apoptosis to necrosis is also
      associated with the increases of VAC. The increase in lysosomal size may due to
      intracellular self-digestion of dying cells. Big lysosomes are easy to rupture,
      and the release of hydrolytic enzymes from ruptured lysosomes can cause plasma
      membrane disruption.

PMID- 12509465
TI  - The transcription factor Rim101p governs ion tolerance and cell differentiation
      by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces
      cerevisiae.
AB  - Environmental pH changes have broad consequences for growth and differentiation.
      The best-understood eukaryotic pH response pathway acts through the zinc-finger
      transcription factor PacC of Aspergillus nidulans, which activates alkaline pH
      induced genes directly. We show here that Saccharomyces cerevisiae Rim101p, the
      pH response regulator homologous to PacC, functions as a repressor in vivo.
      Chromatin immunoprecipitation assays show that Rim101p is associated in vivo with
      the promoters of seven Rim101p-repressed genes. A reporter gene containing
      deduced Rim101p binding sites is negatively regulated by Rim101p and is
      associated with Rim101p in vivo. Deletion mutations of the Rim101p repression
      targets NRG1 and SMP1 suppress rim101Delta mutant defects in ion tolerance,
      haploid invasive growth, and sporulation. Therefore, transcriptional repression
      is the main biological function of Rim101p. The Rim101p repression target Nrg1p
      is in turn required for repression of two alkaline pH-inducible genes, including
      the Na+ pump gene ENA1, which is required for ion tolerance. Thus, Nrg1p, a known
      transcriptional repressor, functions as an inhibitor of alkaline pH responses.
      Our findings stand in contrast to the well-characterized function of PacC as a
      direct activator of alkaline pH-induced genes yet explain many aspects of Rim101p
      and PacC function in other organisms.

PMID- 12509466
TI  - Eukaryotic initiation factors 4G and 4A mediate conformational changes downstream
      of the initiation codon of the encephalomyocarditis virus internal ribosomal
      entry site.
AB  - Initiation of translation of encephalomyocarditis virus mRNA is mediated by an
      internal ribosome entry site (IRES) comprising structural domains H, I, J-K, and
      L immediately upstream of the initiation codon AUG at nucleotide 834 (AUG834).
      Assembly of 48S ribosomal complexes on the IRES requires eukaryotic initiation
      factor 2 (eIF2), eIF3, eIF4A, and the central domain of eIF4G to which eIF4A
      binds. Footprinting experiments confirmed that eIF4G binds a three-way helical
      junction in the J-K domain and showed that it interacts extensively with RNA
      duplexes in the J-K and L domains. Deletion of apical hairpins in the J and K
      domains synergistically impaired the binding of eIF4G and IRES function. Directed
      hydroxyl radical probing, done by using Fe(II) tethered to surface residues in
      eIF4G's central domain, indicated that it is oriented with its N terminus towards
      the base of domain J and its C terminus towards the apex. eIF4G recruits eIF4A to
      a defined location on the IRES, and the eIF4G/eIF4A complex caused localized ATP
      independent conformational changes in the eIF4G-binding region of the IRES. This
      complex also induced more extensive conformational rearrangements at the 3'
      border of the ribosome binding site that required ATP and active eIF4A. We
      propose that these conformational changes prepare the region flanking AUG834 for
      productive binding of the ribosome.

PMID- 12509467
TI  - Autoregulation in the biosynthesis of ribosomes.
AB  - The synthesis of ribosomes in Saccharomyces cerevisiae consumes a prodigious
      amount of the cell's resources and, consequently, is tightly regulated. The rate
      of ribosome synthesis responds not only to nutritional cues but also to signals
      dependent on other macromolecular pathways of the cell, e.g., a defect in the
      secretory pathway leads to severe repression of transcription of both rRNA and
      ribosomal protein genes. A search for mutants that interrupted this repression
      revealed, surprisingly, that inactivation of RPL1B, one of a pair of genes
      encoding the 60S ribosomal protein L1, almost completely blocked the repression
      of rRNA and ribosomal protein gene transcription that usually follows a defect in
      the secretory pathway. Further experiments showed that almost any mutation
      leading to a defect in 60S subunit synthesis had the same effect, whereas
      mutations affecting 40S subunit synthesis did not. Although one might suspect
      that this effect would be due to a decrease in the initiation of translation or
      to the presence of half-mers, i.e., polyribosomes awaiting a 60S subunit, our
      data show that this is not the case. Rather, a variety of experiments suggest
      that some aspect of the production of defective 60S particles or, more likely,
      their breakdown suppresses the signal generated by a defect in the secretory
      pathway that represses ribosome synthesis.

PMID- 12509468
TI  - Heterogeneous nuclear ribonucleoprotein C modulates translation of c-myc mRNA in
      a cell cycle phase-dependent manner.
AB  - The c-myc proto-oncogene plays a key role in the proliferation, differentiation,
      apoptosis, and regulation of the cell cycle. Recently, it was demonstrated that
      the 5' nontranslated region (5' NTR) of human c-myc mRNA contains an internal
      ribosomal entry site (IRES). In this study, we investigated cellular proteins
      interacting with the IRES element of c-myc mRNA. Heterogeneous nuclear
      ribonucleoprotein C (hnRNP C) was identified as a cellular protein that interacts
      specifically with a heptameric U sequence in the c-myc IRES located between two
      alternative translation initiation codons CUG and AUG. Moreover, the addition of
      hnRNP C1 in an in vitro translation system enhanced translation of c-myc mRNA.
      Interestingly, hnRNP C was partially relocalized from the nucleus, where most of
      the hnRNP C resides at interphase, to the cytoplasm at the G(2)/M phase of the
      cell cycle. Coincidently, translation mediated through the c-myc IRES was
      increased at the G(2)/M phase when cap-dependent translation was partially
      inhibited. On the other hand, a mutant c-myc mRNA lacking the hnRNP C-binding
      site, showed a decreased level of translation at the G(2)/M phase compared to
      that of the wild-type message. Taken together, these findings suggest that hnRNP
      C, via IRES binding, modulates translation of c-myc mRNA in a cell cycle phase
      dependent manner.

PMID- 12509469
TI  - Regulation of RelA (p65) function by the large subunit of replication factor C.
AB  - The RelA (p65) subunit of NF-kappaB is an important regulator of inflammation,
      proliferation, and apoptosis. We have discovered that the large subunit, p140, of
      replication factor C (RFC) can function as a regulator of RelA. RFC is a clamp
      loader, facilitating the addition and removal of proliferating-cell nuclear
      antigen from DNA during replication and repair but can also interact directly
      with the retinoblastoma tumor suppressor protein and the transcription factor
      C/EBPalpha. We find that RFC (p140) interacts with RelA both in vitro and in vivo
      and stimulates RelA transactivation. In contrast, coexpression of fragments of
      RFC (p140) that mediate the interaction with RelA results in transcriptional
      inhibition. The significance of this regulation was confirmed by using short
      interfering RNA oligonucleotides targeted to RFC (p140). Down regulation of
      endogenous RFC (p140) inhibits expression from a chromosomally integrated
      reporter plasmid induced by endogenous, TNF-alpha-activated NF-kappaB. Dominant
      negative fragments of RFC (p140) also cooperate with overexpressed RelA to induce
      cell death. Interestingly, RFC (p140) also interacts with the tumor suppressor
      p53. Taken together, these observations suggest that, in addition to its
      previously described function in DNA replication and repair, RFC (p140) has an
      important role as a regulator of transcription and NF-kappaB activity.

PMID- 12509470
TI  - Extensive loss of heterozygosity is suppressed during homologous repair of
      chromosomal breaks.
AB  - Loss of heterozygosity (LOH) is a common genetic alteration in tumors and often
      extends several megabases to encompass multiple genetic loci or even whole
      chromosome arms. Based on marker and karyotype analysis of tumor samples, a
      significant fraction of LOH events appears to arise from mitotic recombination
      between homologous chromosomes, reminiscent of recombination during meiosis. As
      DNA double-strand breaks (DSBs) initiate meiotic recombination, a potential
      mechanism leading to LOH in mitotically dividing cells is DSB repair involving
      homologous chromosomes. We therefore sought to characterize the extent of LOH
      arising from DSB-induced recombination between homologous chromosomes in
      mammalian cells. To this end, a recombination reporter was introduced into a
      mouse embryonic stem cell line that has nonisogenic maternal and paternal
      chromosomes, as is the case in human populations, and then a DSB was introduced
      into one of the chromosomes. Recombinants involving alleles on homologous
      chromosomes were readily obtained at a frequency of 4.6 x 10(-5); however, this
      frequency was substantially lower than that of DSB repair by nonhomologous end
      joining or the inferred frequency of homologous repair involving sister
      chromatids. Strikingly, the majority of recombinants had LOH restricted to the
      site of the DSB, with a minor class of recombinants having LOH that extended to
      markers 6 kb from the DSB. Furthermore, we found no evidence of LOH extending to
      markers 1 centimorgan or more from the DSB. In addition, crossing over, which can
      lead to LOH of a whole chromosome arm, was not observed, implying that there are
      key differences between mitotic and meiotic recombination mechanisms. These
      results indicate that extensive LOH is normally suppressed during DSB-induced
      allelic recombination in dividing mammalian cells.

PMID- 12509471
TI  - Role of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophy.
AB  - Peroxisomal disorders have been associated with malfunction of peroxisomal
      metabolic pathways, but the pathogenesis of these disorders is largely unknown. X
      linked adrenoleukodystrophy (X-ALD) is associated with elevated levels of very
      long-chain fatty acids (VLCFA; C(>22:0)) that have been attributed to reduced
      peroxisomal VLCFA beta-oxidation activity. Previously, our laboratory and others
      have reported elevated VLCFA levels and reduced peroxisomal VLCFA beta-oxidation
      in human and mouse X-ALD fibroblasts. In this study, we found normal levels of
      peroxisomal VLCFA beta-oxidation in tissues from ALD mice with elevated VLCFA
      levels. Treatment of ALD mice with pharmacological agents resulted in decreased
      VLCFA levels without a change in VLCFA beta-oxidation activity. These data
      indicate that ALDP does not determine the rate of VLCFA beta-oxidation and that
      VLCFA levels are not determined by the rate of VLCFA beta-oxidation. The rate of
      peroxisomal VLCFA beta-oxidation in human and mouse fibroblasts in vitro is
      affected by the rate of mitochondrial long-chain fatty acid beta-oxidation. We
      hypothesize that ALDP facilitates the interaction between peroxisomes and
      mitochondria, resulting, when ALDP is deficient in X-ALD, in increased VLCFA
      accumulation despite normal peroxisomal VLCFA beta-oxidation in ALD mouse
      tissues. In support of this hypothesis, mitochondrial structural abnormalities
      were observed in adrenal cortical cells of ALD mice.

PMID- 12509472
TI  - Nucleotide excision repair- and polymerase eta-mediated error-prone removal of
      mitomycin C interstrand cross-links.
AB  - Interstrand cross-links (ICLs) make up a unique class of DNA lesions in which
      both strands of the double helix are covalently joined, precluding strand opening
      during replication and transcription. The repair of DNA ICLs has become a focus
      of study since ICLs are recognized as the main cytotoxic lesion inflicted by an
      array of alkylating compounds used in cancer treatment. As is the case for double
      strand breaks, a damage-free homologous copy is essential for the removal of ICLs
      in an error-free manner. However, recombination-independent mechanisms may exist
      to remove ICLs in an error-prone fashion. We have developed an in vivo
      reactivation assay that can be used to examine the removal of site-specific
      mitomycin C-mediated ICLs in mammalian cells. We found that the removal of the
      ICL from the reporter substrate could take place in the absence of undamaged
      homologous sequences in repair-proficient cells, suggesting a cross-link repair
      mechanism that is independent of homologous recombination. Systematic analysis of
      nucleotide excision repair mutants demonstrated the involvement of transcription
      coupled nucleotide excision repair and a partial requirement for the lesion
      bypass DNA polymerase eta encoded by the human POLH gene. From these
      observations, we propose the existence of a recombination-independent and
      mutagenic repair pathway for the removal of ICLs in mammalian cells.

PMID- 12509473
TI  - Presynaptic dendrites of thalamic local-circuit neurons and sculpting inhibition
      during activated states.

PMID- 12509474
TI  - Normal and pathological excitation-contraction coupling in the heart -- an
      overview.
AB  - This issue of The Journal of Physiology includes a series of review articles
      arising from a symposium held at the joint meeting of the UK, German and
      Scandinavian Physiological Societies. The articles focus on different aspects of
      the cellular control of contraction. The basic mechanism of cardiac excitation
      contraction coupling ('calcium-induced calcium release') is now reasonably well
      established. Calcium enters the cell from the extracellular fluid via the voltage
      dependent L-type Ca(2+) channel. This results in a 'trigger' increase of
      [Ca(2+)](i) in the space between the sarcolemma and sarcoplasmic reticulum (SR)
      and this leads to the opening of the SR Ca(2+) release channel or 'ryanodine
      receptor' (RyR). As exemplified by the papers from the symposium, much current
      work is focused on how this mechanism is modified in different circumstances.
      These include autonomic modulation, but also pathological conditions such as
      cardiac hypertrophy and failure, a recurrent theme in several of these papers.

PMID- 12509475
TI  - Regulation of cardiac excitation-contraction coupling by action potential
      repolarization: role of the transient outward potassium current (I(to)).
AB  - The cardiac action potential (AP) is critical for initiating and coordinating
      myocyte contraction. In particular, the early repolarization period of the AP
      (phase 1) strongly influences the time course and magnitude of the whole-cell
      intracellular Ca(2+) transient by modulating trans-sarcolemmal Ca(2+) influx
      through L-type Ca(2+) channels (I(Ca,L)) and Na-Ca exchangers (I(Ca,NCX)). The
      transient outward potassium current (I(to)) has kinetic properties that make it
      especially effective in modulating the trajectory of phase 1 repolarization and
      thereby cardiac excitation-contraction coupling (ECC). The magnitude of I(to)
      varies greatly during cardiac development, between different regions of the
      heart, and is invariably reduced as a result of heart disease, leading to
      corresponding variations in ECC. In this article, we review evidence supporting a
      modulatory role of I(to) in ECC through its influence on I(Ca,L), and possibly
      I(Ca,NCX). We also discuss differential effects of I(to) on ECC between different
      species, between different regions of the heart and in heart disease.

PMID- 12509476
TI  - Local calcium gradients during excitation-contraction coupling and alternans in
      atrial myocytes.
AB  - Subcellular Ca(2+) signalling during normal excitation-contraction (E-C) coupling
      and during Ca(2+) alternans was studied in atrial myocytes using fast confocal
      microscopy and measurement of Ca(2+) currents (I(Ca)). Ca(2+) alternans, a beat
      to-beat alternation in the amplitude of the [Ca(2+)](i) transient, causes
      electromechanical alternans, which has been implicated in the generation of
      cardiac fibrillation and sudden cardiac death. Cat atrial myocytes lack
      transverse tubules and contain sarcoplasmic reticulum (SR) of the junctional (j
      SR) and non-junctional (nj-SR) types, both of which have ryanodine-receptor
      calcium release channels. During E-C coupling, Ca(2+) entering through voltage
      gated membrane Ca(2+) channels (I(Ca)) triggers Ca(2+) release at discrete
      peripheral j-SR release sites. The discrete Ca(2+) spark-like increases of
      [Ca(2+)](i) then fuse into a peripheral 'ring' of elevated [Ca(2+)](i), followed
      by propagation (via calcium-induced Ca(2+) release, CICR) to the cell centre,
      resulting in contraction. Interrupting I(Ca) instantaneously terminates j-SR
      Ca(2+) release, whereas nj-SR Ca(2+) release continues. Increasing the
      stimulation frequency or inhibition of glycolysis elicits Ca(2+) alternans. The
      spatiotemporal [Ca(2+)](i) pattern during alternans shows marked subcellular
      heterogeneities including longitudinal and transverse gradients of [Ca(2+)](i)
      and neighbouring subcellular regions alternating out of phase. Moreover, focal
      inhibition of glycolysis causes spatially restricted Ca(2+) alternans, further
      emphasising the local character of this phenomenon. When two adjacent regions
      within a myocyte alternate out of phase, delayed propagating Ca(2+) waves develop
      at their border. In conclusion, the results demonstrate that (1) during normal E
      C coupling the atrial [Ca(2+)](i) transient is the result of the spatiotemporal
      summation of Ca(2+) release from individual release sites of the peripheral j-SR
      and the central nj-SR, activated in a centripetal fashion by CICR via I(Ca) and
      Ca(2+) release from j-SR, respectively, (2) Ca(2+) alternans is caused by
      subcellular alterations of SR Ca(2+) release mediated, at least in part, by local
      inhibition of energy metabolism, and (3) the generation of arrhythmogenic Ca(2+)
      waves resulting from heterogeneities in subcellular Ca(2+) alternans may
      constitute a novel mechanism for the development of cardiac dysrhythmias.

PMID- 12509477
TI  - Heart failure -- a challenge to our current concepts of excitation-contraction
      coupling.
AB  - Development of novel therapeutic strategies for congestive heart failure (CHF)
      seems to be hampered by insufficient knowledge of the molecular machinery of
      excitation-contraction (EC) coupling in both normal and failing hearts. Cardiac
      hypertrophy and failure represent a multitude of cardiac phenotypes, and
      available invasive and non-invasive techniques, briefly reviewed here, allow
      proper quantification of myocardial function in experimental models even in rats
      and mice. Both reduced fractional shortening and reduced velocity of contraction
      characterize myocardial failure. Only when myocardial function is depressed in
      vivo can meaningful studies be done in vitro of contractility and EC coupling.
      Also, we point out potential limitations with the whole cell patch clamp
      technique. Two main factors stand out as explanations for myocardial failure.
      First, a basic feature of CHF seems to be a reduced Ca(2+) load of the
      sarcoplasmic reticulum (SR) mainly due to a low phosphorylation level of
      phospholamban. Second, there seems to be a defect of the trigger mechanism of
      Ca(2+) release from the SR. We argue that this defect only becomes manifest in
      the presence of reduced Ca(2+) reuptake capacity of the SR and that it may not be
      solely attributable to reduced gain of the Ca(2+)-induced Ca(2+) release (CICR).
      We list several possible explanations for this defect that represent important
      avenues for future research.

PMID- 12509478
TI  - Targeting calcium cycling proteins in heart failure through gene transfer.
AB  - Our understanding of cardiac excitation-contraction coupling has improved
      significantly over the last 10 years. Furthermore, defects in the various steps
      of excitation-contraction coupling that characterize cardiac dysfunction have
      been identified in human and experimental models of heart failure. The various
      abnormalities in ionic channels, transporters, kinases and various signalling
      pathways collectively contribute to the 'failing phenotype.' However, deciphering
      the causative changes continues to be a challenge. An important tool in
      dissecting the importance of the various changes in heart failure has been the
      use of cardiac gene transfer. To achieve effective cardiac gene transfer a number
      of obstacles remain, including appropriate vectors for gene delivery, appropriate
      delivery systems, and a better understanding of the biology of the disease. In
      this review, we will examine our current understanding of these various factors.
      Gene transfer provides not only a potential therapeutic modality but also an
      approach to identifying and validating molecular targets.

PMID- 12509479
TI  - Modulation of cardiac contraction, relaxation and rate by the endothelial nitric
      oxide synthase (eNOS): lessons from genetically modified mice.
AB  - The modulatory role of endothelial nitric oxide synthase (eNOS) on heart
      contraction, relaxation and rate is examined in light of recent studies using
      genetic deletion or overexpression in mice under specific conditions. Unstressed
      eNOS-/- hearts in basal conditions exhibit a normal inotropic and lusitropic
      function, with either decreased or unchanged heart rate. Under stimulation with
      catecholamines, eNOS-/- mice predominantly show a potentiation in their beta
      adrenergic inotropic and lusitropic responsiveness. A similar phenotype is
      observed in beta 3-adrenoceptor deficient mice, pointing to a key role of this
      receptor subtype for eNOS coupling. The effect of eNOS on the muscarinic
      cholinergic modulation of cardiac function probably operates in conjunction with
      other NO-independent mechanisms, the persistence of which may explain the
      apparent dispensability of this isoform for the effect of acetylcholine in some
      eNOS-/- mouse strains. eNOS-/- hearts submitted to short term ischaemia
      reperfusion exhibit variable alterations in systolic and diastolic function and
      infarct size, while those submitted to myocardial infarction present a worsened
      ventricular remodelling, increased 1 month mortality and loss of benefit from ACE
      inhibitor or angiotensin II type I receptor antagonist therapy. Although non
      conditional eNOS gene deletion may engender phenotypic adaptations (e.g.
      ventricular hypertrophy resulting from chronic hypertension, or upregulation of
      the other NOS isoforms) potentially confounding the interpretation of comparative
      studies, the use of eNOS-/- mice has undoubtedly advanced (and will probably
      continue to improve) our understanding of the complex role of eNOS (in
      conjunction with the other NOSs) in the regulation of cardiac function. The
      challenge is now to confirm the emerging paradigms in human cardiac physiology
      and hopefully translate them into therapy.

PMID- 12509480
TI  - Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian
      central nervous system.
AB  - The acid-sensitive ion channel ASIC1 is a proton-gated ion channel from the
      mammalian nervous system. Its expression in sensory neurons and activation by low
      extracellular pH suggest that ASIC is involved in transmitting nociceptive
      impulses produced by the acidification caused by injury or inflammation. However,
      ASIC1 expression is not restricted to sensory neurons. To understand the
      functional role of ASIC1 in the CNS we investigated its expression and
      subcellular distribution therein. In particular, we examined the presence of
      ASIC1 in domains where the local pH may drop sufficiently to activate ASIC1 under
      physiological conditions. Immunostaining with specific antibodies revealed broad
      expression of ASIC1 in many areas of the adult rat brain including the cerebral
      cortex, hippocampus and cerebellum. Within cells, ASIC1 was found predominantly
      throughout the soma and along the branches of axons and dendrites. ASIC1 was not
      enriched in the microdomains where pH may reach low values, such as in synaptic
      vesicles or synaptic membranes. Pre- or postsynaptic ASIC1 was not gated by
      synaptic activity in cultured hippocampal neurons. Blockage or desensitization of
      ASIC1 with amiloride or pH 6.7, respectively, did not modify postsynaptic
      currents. Finally, the ontogeny of ASIC1 in mouse brain revealed constant levels
      of expression of ASIC1 protein from embryonic day 12 to the postnatal period,
      indicating an early and almost constant level of expression of ASIC1 during brain
      development.

PMID- 12509481
TI  - Intracellular sodium changes during the speract response and the acrosome
      reaction in sea urchin sperm.
AB  - The sperm-activating peptide speract and fucose-sulphate glycoconjugate (FSG) are
      sea urchin egg-envelope components that modulate sperm ion permeability. They
      influence motility and induce acrosomal reaction (AR), respectively. A
      fluorescent Na(+)-sensitive dye (Na(+)-binding benzofuran isophthalate, SBFI) was
      used to determine how these egg envelope components influence sperm Na(+)
      permeability. [Ca(2+)](i) and pH(i) were also measured to correlate their changes
      in response to speract and FSG with those observed in [Na(+)](i). SBFI
      determinations indicate that the resting [Na(+)](i) is 20 +/- 8 mM in sea urchin
      sperm. Saturating levels of speract increased [Na(+)](i) by approximately 15 mM,
      while similar levels of FSG caused a further elevation of approximately 30 mM.
      The kinetics of the [Na(+)](i), [Ca(2+)](i) and pH(i) changes induced by
      saturating levels of speract were faster than those induced by FSG. Both egg
      ligands appeared to activate more than one Na(+) transport system. Nifedipine,
      Ni(2+) and TEA(+) inhibited the ionic changes and the AR induced by FSG but,
      importantly, did not alter those caused by speract. Thus, there are differences
      in some of the ionic transport mechanisms that operate in the speract and FSG
      responses. ZD2788, a blocker of hyperpolarization and cyclic-nucleotide-gated
      (HCN) channels such as SpHCN present in sea urchin sperm, did not decrease the
      speract-induced [Na(+)](i) increase, but slowed its kinetics. Therefore, SpHCN
      does not play a major role in the uptake of Na(+) triggered by this decapeptide.
      KB-R7943, an inhibitor of Na(+)/Ca(2+) exchangers, decreased the resting
      [Na(+)](i) and did not change significantly the speract-induced [Ca(2+)](i)
      increase, but slowed its recovery.

PMID- 12509482
TI  - AMPA-sst2 somatostatin receptor interaction in rat hypothalamus requires
      activation of NMDA and/or metabotropic glutamate receptors and depends on
      intracellular calcium.
AB  - Modulation of glutamatergic transmission by neuropeptides is an essential aspect
      of neuronal network activity. Activation of the hypothalamic somatostatin sst2
      receptor subtype by octreotide decreases AMPA glutamate responses, indicating a
      central link between a neurohormonal and neuromodulatory peptide and the main
      hypothalamic fast excitatory neurotransmitter. In mediobasal hypothalamic slices,
      sst2 activation inhibits the AMPA component of glutamatergic synaptic responses
      but is ineffective when AMPA currents are pharmacologically isolated. In
      mediobasal hypothalamic cultures, the decrease of AMPA currents induced by
      octreotide requires a concomitant activation of sst2 receptors with either NMDA
      and/or metabotropic glutamate receptors. This modulation depends on changes in
      intracellular calcium concentration induced by calcium flux through NMDA
      receptors or calcium release from intracellular stores following metabotropic
      glutamate receptor activation. These results highlight an unusual regulatory
      mechanism in which the simultaneous activation of at least three different types
      of receptor is necessary to allow somatostatin-induced modulation of fast
      synaptic glutamatergic transmission in the hypothalamus.

PMID- 12509483
TI  - Regulation of junctional and non-junctional sarcoplasmic reticulum calcium
      release in excitation-contraction coupling in cat atrial myocytes.
AB  - We have characterized the dependence on membrane potential (V(m)) and calcium
      current (I(Ca)) of calcium-induced calcium release (CICR) from the junctional-SR
      (j-SR, in the subsarcolemmal (SS) space) and non-junctional-SR (nj-SR, in the
      central (CT) region of the cell) of cat atrial myocytes using whole-cell voltage
      clamp together with spatially resolved laser-scanning confocal microscopy.
      Subsarcolemmal and central [Ca(2+)](i) transient amplitudes and I(Ca) had a bell
      shaped dependence on V(m), but [Ca(2+)](i) reached a maximum at more negative
      V(m) (-10 to 0 mV) than I(Ca) (+10 mV). Termination of I(Ca) after a brief
      depolarization (2.5 to 22.5 ms) immediately interrupted only the SS [Ca(2+)](i)
      transient, leaving the development of the CT [Ca(2+)](i) transient unaffected.
      Block of SR function with 20 microM ryanodine and 2 microM thapsigargin, revealed
      that > 90 % of the control [Ca(2+)](i) transient amplitude was attributable to
      active SR Ca(2+) release through ryanodine receptors (RyRs). The gain of SR
      Ca(2+) release was highest in the SS space at negative test potentials and was
      less pronounced in the CT region. Inhibition of Na(+)-Ca(2+) exchange resulted in
      prolonged and higher amplitude [Ca(2+)](i) transients, elevated resting
      [Ca(2+)](i), accelerated propagation of CICR, decreased extrusion of Ca(2+) and
      an increase in j-SR Ca(2+) load. Increasing the cytosolic Ca(2+) buffer capacity
      by internal perfusion with 1 mM EGTA limited SR Ca(2+) release to the SS region,
      indicating that Ca(2+) release from nj-SR is initiated by diffusion of Ca(2+)
      from the cell periphery and propagating CICR. Junctional-SR Ca(2+) release
      occurred at discrete sites whose order of activation and amplitude of release
      varied from beat to beat. In conclusion, during normal excitation-contraction
      coupling in cat atrial myocytes, only Ca(2+) release from the j-SR is directly
      activated by Ca(2+) entering via I(Ca). Elevation of SS [Ca(2+)](i) is required
      to provide the cytosolic Ca(2+) gradient needed to initiate regenerative and
      propagating CICR from nj-SR.

PMID- 12509484
TI  - Postnatal development of GABAergic signalling in the rat lateral geniculate
      nucleus: presynaptic dendritic mechanisms.
AB  - Diverse forms of GABAergic inhibition are found in the mature brain. To
      understand how this diversity develops, we studied the changes in morphology of
      inhibitory interneurons and changes in interneuron-mediated synaptic transmission
      in the rat dorsal lateral geniculate nucleus (dLGN). We found a steady expansion
      of the dendritic tree of interneurons over the first three postnatal weeks.
      During this period, the area around a thalamocortical cell from which GABA(A)
      inhibition could be elicited also expanded. Dendritic branching and burst firing
      in interneurons evolved more slowly. The distal dendrites of interneurons began
      to branch extensively after the third week, and at the same time burst firing
      appeared. The appearance of burst firing and an elaborated dendritic tree were
      accompanied by a pronounced GABA(B) inhibition of thalamocortical cells. Thus,
      GABA inhibition of thalamocortical cells developed from one type of GABA(A)
      inhibition (spatially restricted) in the young animal into two distinct types of
      GABA(A) inhibition (short- and long-range) and GABA(B) inhibition in the adult
      animal. The close temporal relationships between the development of the diverse
      forms of inhibition and the postnatal changes in morphology of local GABAergic
      interneurons in the dLGN suggest that postnatal dendritic maturation is an
      important presynaptic factor for the developmental time course of the various
      types of feedforward inhibition in thalamus.

PMID- 12509485
TI  - Effects of oxidation and reduction on contractile function in skeletal muscle
      fibres of the rat.
AB  - This study investigated the effects of the oxidants hydrogen peroxide (H(2)O(2))
      and 2,2'-dithiodipyridine (DTDP), and reductants, glutathione (GSH) and
      dithiothreitol (DTT), on the properties of the contractile apparatus of rat fast-
      and slow-twitch skeletal muscle fibres, in order to assess how oxidation affects
      muscle function. Skinned muscle fibres were activated in heavily-buffered Ca(2+)
      solutions. The force-[Ca(2+)] relationship before and after various treatments
      was fitted by a Hill curve described by the maximum Ca(2+)-activated force,
      pCa(50) (-log(10)[Ca(2+)] giving half-maximum force) and n(H) (the Hill
      coefficient). Exposing freshly skinned fibres to strong reducing conditions (i.e.
      10 mM DTT or 5 mM GSH) had little if any effect on Ca(2+) sensitivity (pCa(50) or
      n(H)). The effect of oxidants H(2)O(2) and DTDP depended on whether the fibre was
      relaxed (in pCa > 9) or activated during the exposure. In both fast- and slow
      twitch fibres a 5 min exposure to 10 mM H(2)O(2) at pCa > 9 had no effect on
      pCa(50), causing only a reduction in n(H). In contrast, when fast-twitch fibres
      were activated in the presence of 10 mM H(2)O(2) (or 100 microM DTDP) there was a
      substantial increase in pCa(50) (by approximately 0.06 and 0.1, respectively), as
      well as larger decreases in n(H) than occurred in relaxed fibres, with all
      effects being reversed by DTT (10 mM, 10 min). In slow-twitch soleus fibres, the
      activation-dependent effect of DTDP was even greater (pCa(50) increased by
      ~0.35), and it was found that the rate of reversal in DTT was also increased by
      activation. A separate important phenomenon was that fast-twitch fibres that had
      been oxidised with H(2)O(2) or DTDP (while either relaxed or activated) showed a
      paradoxical increase in Ca(2+) sensitivity (~0.04 and 0.25 increase in pCa(50),
      respectively) when briefly exposed to the endogenous reductant GSH (5 mM, 2 min).
      This effect was reversed by DTT or longer (> 20 min) exposure to GSH, did not
      occur in slow-twitch soleus fibres, and may contribute to post-tetanic
      potentiation in fast-twitch muscle. Maximum force was not affected by any of the
      above treatments, whereas exposure to a high concentration of DTDP (1 mM) did
      greatly reduce force production. These findings reveal a number of novel and
      probably important effects of oxidation on the contractile apparatus in skeletal
      muscle fibres.

PMID- 12509486
TI  - Chronic acetylcholinesterase overexpression induces multilevelled aberrations in
      mouse neuromuscular physiology.
AB  - Chronic overexpression of the acetylcholine-hydrolysing enzyme
      acetylcholinesterase (AChE) is a notable consequence of exposure to
      anticholinesterase drugs or poisons. However, the physiological consequences for
      the resultant neuromuscular disfunction have not yet been carefully analysed.
      Here we report detailed dissection of the different components of neuromuscular
      function in transgenic mice previously shown to display motor fatigue and altered
      muscle morphology as a consequence of neuronal overexpression of AChE-S, the
      synaptic AChE variant. Transgenic diaphragm muscle presented exaggerated fatigue
      as a combined consequence of neurotransmission fading and muscle mechanical
      malfunctioning. In a tetanic stimulation protocol, transgenic muscles rapidly
      fatigued to a larger extent than wild-type muscles, when stimulated either
      directly or via the phrenic nerve. AChE overexpression involved moderate but
      significant aberrations of synaptic transmission with higher quantal content
      (measured at 0.2 mM Ca(2+), 2.3 mM Mg(2+)). Furthermore, treatment with the anti
      cholinesterase physostigmine revealed a higher amplitude and half-decay time of
      the transgenic quantal postsynaptic response. Our observations imply that
      elevated levels of neuronal AChE-S are expected to cause muscle exhaustion due to
      a combination of modest, multilevelled aberrations in synaptic transmission,
      muscle function and morphology.

PMID- 12509487
TI  - Amplification of exocytosis by Ca2+-induced Ca2+ release in INS-1 pancreatic beta
      cells.
AB  - Functional coupling between Ca(2+)-induced Ca(2+) release (CICR) and quantal
      exocytosis in 5-hydroxytryptamine-loaded INS-1 beta cells was assessed through
      the use of carbon fibre amperometry in combination with Fura-2. CICR was evoked
      by the glucagon-like-peptide-1 (GLP-1) receptor agonist exendin-4 (Ex-4) and was
      accompanied by quantal secretory events appearing as amperometric current spikes
      time-locked to the increase of [Ca(2+)](i). The action of Ex-4 was reproduced by
      treatment with caffeine, and the source of Ca(2+) serving as a stimulus for
      exocytosis originated from ryanodine and thapsigargin-sensitive Ca(2+) stores.
      Two distinct patterns of exocytosis occurred within 5 s following the initiation
      of CICR. Non-summating exocytosis (NS-type) was defined as multiple asynchronous
      current spikes, and the half-height duration of each spike was 12-48 ms.
      Summating exocytosis (S-type) was defined as a cluster of spikes. It generated a
      macroscopic current, the half-height duration of which was 243-682 ms. The
      release charge of S-type exocytosis was 3.2-fold greater than that of NS-type
      when measured 2 s following the initiation of secretion. NS-type exocytosis was
      observed frequently under conditions in which the basal Ca(2+) concentration
      ([Ca(2+)](B)) was low (75-150 nM), whereas S-type exocytosis predominated under
      conditions in which the [Ca(2+)](B) was elevated (200-275 nM). Depolarization
      induced Ca(2+) influx triggered NS-type exocytosis in most cells tested,
      irrespective of [Ca(2+)](B). It is concluded that CICR is a highly effective
      stimulus for exocytosis in INS-1 cells. The increase of [Ca(2+)](i) that
      accompanies CICR stimulates the asynchronous release of a small number of
      secretory granules under conditions of low [Ca(2+)](B). When [Ca(2+)](B) is
      slightly elevated, CICR targets a much larger pool of secretory granules that
      undergo summating exocytosis. The transition from NS-type to S-type exocytosis
      may represent an amplification mechanism for Ca(2+)-dependent exocytosis.

PMID- 12509488
TI  - Pacemaker frequency is increased by sodium nitroprusside in the guinea pig
      gastric antrum.
AB  - In the guinea pig gastric antrum, the effects of sodium nitroprusside (SNP), an
      NO donor, on pacemaker potentials were investigated in the presence of
      nifedipine. The pacemaker potentials consisted of primary and plateau components;
      SNP (> 1 microM) increased the frequency of occurrence of these pacemaker
      potentials, while inhibiting the plateau component. 1H-[1,2,4]-Oxadiazole [4,3-a]
      quinoxalin-1-one, an inhibitor of guanylate cyclase, had no effect on the
      excitatory actions of SNP on the frequency of pacemaker potentials. Other types
      of NO donor, (+/-)-S-nitroso-N-acetylpenicillamine, 3-morpholino-sydnonimine and
      8-bromoguanosine 3'5'-cyclic monophosphate had no excitatory effect on pacemaker
      activity. Forskolin, an activator of adenylate cyclase, or 4,4'-diisothiocyano
      stilbene-2,2'-disulphonic acid, an inhibitor of the Ca(2+)-activated Cl(-)
      channel, strongly attenuated the generation of pacemaker potentials, and SNP
      added in the presence of these chemicals restored the generation of pacemaker
      potentials. The pacemaker potentials evoked by SNP were abolished in low-Ca(2+)
      solution or by membrane depolarization with high-K(+) solution. The SNP-induced
      generation of pacemaker potentials was not prevented by cyclopiazonic acid, an
      inhibitor of internal Ca(2+)-ATPase, but was limited to a transient burst by
      iodoacetic acid, an inhibitor of glycolysis, carbonyl cyanide m-chlorophenyl
      hydrazone, a mitochondrial protonophore, or 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid acetoxymethyl ester, an intracellular Ca(2+) chelator.
      These results suggest that the SNP-induced increase in the frequency of pacemaker
      potentials is related to the elevated intracellular Ca(2+) concentrations due to
      release from mitochondria, and these actions may be independent of the activation
      of guanylate cyclase.

PMID- 12509489
TI  - Firing behaviour of squirrel monkey eye movement-related vestibular nucleus
      neurons during gaze saccades.
AB  - The firing behaviour of vestibular nucleus neurons putatively involved in
      producing the vestibulo-ocular reflex (VOR) was studied during active and passive
      head movements in squirrel monkeys. Single unit recordings were obtained from 14
      position-vestibular (PV) neurons, 30 position-vestibular-pause (PVP) neurons and
      9 eye-head-vestibular (EHV) neurons. Neurons were sub-classified as type I or II
      based on whether they were excited or inhibited during ipsilateral head rotation.
      Different classes of cell exhibited distinctive responses during active head
      movements produced during and after gaze saccades. Type I PV cells were nearly as
      sensitive to active head movements as they were to passive head movements during
      saccades. Type II PV neurons were insensitive to active head movements both
      during and after gaze saccades. PVP and EHV neurons were insensitive to active
      head movements during saccadic gaze shifts, and exhibited asymmetric sensitivity
      to active head movements following the gaze shift. PVP neurons were less
      sensitive to on-direction head movements during the VOR after gaze saccades,
      while EHV neurons exhibited an enhanced sensitivity to head movements in their on
      direction. Vestibular signals related to the passive head movement were
      faithfully encoded by vestibular nucleus neurons. We conclude that central VOR
      pathway neurons are differentially sensitive to active and passive head movements
      both during and after gaze saccades due primarily to an input related to head
      movement motor commands. The convergence of motor and sensory reafferent inputs
      on VOR pathways provides a mechanism for separate control of eye and head
      movements during and after saccadic gaze shifts.

PMID- 12509490
TI  - Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal
      phenotype in exercise-trained mice.
AB  - We investigated whether enhanced cardiac vagal responsiveness elicited by
      exercise training is dependent on neuronal nitric oxide synthase (NOS-1), since
      the NO-cGMP pathway facilitates acetylcholine release. Isolated atria with intact
      right vagal innervation were taken from male mice (18-22 weeks old) after a
      period of 10 weeks voluntary wheel-running (+EX, n = 27; peaked 9.8 +/- 0.6 km
      day(-1) at 5 weeks), and from mice housed in cages without wheels (-EX, n = 27).
      Immunostaining of whole atria for NOS-1 identified intrinsic neurones, all of
      which co-localized with choline acetyltransferase-positive ganglia. Western blot
      analysis confirmed that NOS-1 protein level was significantly greater in +EX
      compared to -EX atria (P < 0.05, unpaired t test). Basal heart rates (HR) were
      slower in +EX than in -EX atria (322 +/- 6 versus 360 +/- 7 beats min(-1); P <
      0.05, unpaired t test) However, in +EX atria, HR responses to vagal stimulation
      (VNS, 3 and 5 Hz) were significantly enhanced compared to -EX atria (3 Hz, +EX: 
      76 +/- 8 beats min(-1) versus -EX: -62 +/- 7 beats min(-1); 5 Hz, +EX: -106 +/- 4
      beats min(-1) versus -EX: -93 +/- 3 beats min(-1); P < 0.01, unpaired t test).
      Inhibition of NOS-1 with vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO, 100
      microM) or soluble guanylyl cyclase with 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin
      1-one (ODQ, 10 microM) abolished the difference in HR responses to VNS between
      +EX and -EX atria, and effects of L-VNIO were reversed by excess L-arginine (1
      mM; P < 0.01, ANOVA). There were no differences between the HR responses to the
      bath-applied acetylcholine analogue carbamylcholine chloride in +EX and -EX atria
      (IC(50) concentrations were 5.9 +/- 0.4 microM (-EX) and 5.7 +/- 0.4 microM
      (+EX)), suggesting that the changes in vagal responsiveness resulted from
      presynaptic facilitation of neurotransmission. In conclusion, NOS-1 appears to be
      a key protein in generating the cardiac vagal gain of function elicited by
      exercise training.

PMID- 12509491
TI  - Chronic inhibition of endothelial nitric oxide synthase activity in nucleus
      tractus solitarii enhances baroreceptor reflex in conscious rats.
AB  - In acute experiments, we demonstrated previously that nitric oxide (NO) donors
      exogenously applied to the nucleus tractus solitarii (NTS) depressed the
      baroreceptor cardiac reflex. In this study, we determined a role for endogenous
      endothelial nitric oxide synthase (eNOS) activity in the NTS for chronically
      regulating baroreceptor reflex function in conscious rats. A recombinant
      adenoviral vector directing expression of a truncated form of eNOS was
      microinjected bilaterally into the NTS to inhibit endogenous eNOS activity.
      Arterial pressure was monitored continuously using radio-telemetry in freely
      moving animals and spontaneous baroreceptor reflex gain (sBRG) determined by a
      time-series method. sBRG showed a gradual increase from day 7 to 21 after gene
      transfer and the value at day 21 (1.68 +/- 0.20 ms mmHg(-1), n = 6) was
      significantly higher than that before gene transfer (1.13 +/- 0.09 ms mmHg(-1), P
      < 0.001). This value was also significantly higher than that in rats in which
      enhanced green fluorescent protein (eGFP) was expressed in the NTS (1.04 +/- 0.21
      ms mmHg(-1); n = 6, P < 0.01) and saline-treated groups (1.12 +/- 0.15 ms mmHg(
      1); n = 4, P < 0.05), which did not change from control levels. In addition,
      heart rate decreased from 336 +/- 6 to 318 +/- 8 b.p.m. (P < 0.05) 21 days after
      gene transfer. This value was also significantly lower than that in control
      groups (eGFP: 348 +/- 9 b.p.m., n = 6, P < 0.01; saline: 347 +/- 5 b.p.m., n = 4,
      P < 0.05). Gene transfer did not affect arterial pressure. These findings suggest
      that in the conscious rat eNOS is constitutively active within the NTS and is a
      factor regulating baroreceptor reflex gain and heart rate.

PMID- 12509492
TI  - Microinjection of muscimol into raphe pallidus suppresses tachycardia associated
      with air stress in conscious rats.
AB  - Sympathetically mediated tachycardia is a characteristic feature of the
      physiological response to emotional or psychological stress in mammals.
      Activation of neurons in the region of the dorsomedial hypothalamus appears to
      play a key role in the integration of this response. Tachycardia evoked by
      chemical stimulation of the dorsomedial hypothalamus can be suppressed by
      microinjection of the GABA(A) receptor agonist and neuronal inhibitor muscimol
      into the raphe pallidus (RP). Therefore, we tested the hypothesis that neuronal
      excitation in the RP mediates tachycardia seen in experimental air stress in
      rats. Microinjection of the GABA(A) receptor antagonist bicuculline methiodide
      (BMI) into the RP evoked increases in heart rate. At the same sites,
      microinjection of muscimol (80 pmol (100 nl)(-1)) had no effect on heart rate
      under baseline conditions but virtually abolished air stress-induced tachycardia,
      while microinjection of lower doses (10 or 20 pmol) produced transient but clear
      suppression. Microinjection of muscimol at sites outside the RP had no effect on
      stress-induced tachycardia, although modest suppression was apparent after
      injection at two sites within 500 microm of the RP. In another series of
      experiments, microinjection of muscimol (80 pmol (100 nl)(-1)) into the RP failed
      to influence the changes in heart rate produced by baroreceptor loading or
      unloading. These findings indicate that activity of neurons in the RP plays a
      previously unrecognized role in the generation of stress-induced tachycardia.

PMID- 12509493
TI  - Organisation of sensitisation of hind limb withdrawal reflexes from acute noxious
      stimuli in the rabbit.
AB  - Spatial aspects of central sensitisation were investigated by studying the
      effects on three hind limb withdrawal reflexes of an acute noxious stimulus (20 %
      mustard oil) applied to a number of locations around the body in decerebrate and
      in anaesthetised rabbits. Reflex responses to electrical stimulation of the toes
      were recorded from the ankle flexor tibialis anterior (TA) and the knee flexor
      semitendinosus (ST), whereas responses to stimulation of the heel were recorded
      from the ankle extensor medial gastrocnemius (MG). In non-spinalised,
      decerebrated, pentobarbitone-sedated preparations, flexor reflexes were
      facilitated significantly from sites on the plantar surface of the ipsilateral
      foot but were either inhibited or unaffected by stimulation of sites away from
      this location. The heel-MG reflex was facilitated from the ipsilateral heel and
      was inhibited from a number of ipsilateral, contralateral and off-limb sites. In
      decerebrated, spinalised, pentobarbitone-sedated animals, mustard oil applied to
      any site on the ipsilateral hind limb enhanced both flexor reflexes, whereas the
      MG reflex was enhanced only after stimulation at the ipsilateral heel and was
      inhibited after stimulation of the toe tips or TA muscle. Mustard oil on the
      contralateral limb had no effect on any reflex. In rabbits anaesthetised with
      pentobarbitone and prepared with minimal surgical interference, the sensitisation
      fields for the heel-MG and toes-TA reflexes were very similar to those in non
      spinal decerebrates whereas that for toes-ST was more like the pattern observed
      in spinalised animals. In no preparation was sensitisation or inhibition of
      reflexes related to the degree of motoneurone activity generated in direct
      response to the sensitising stimulus. This study provides for the first time a
      complete description of the sensitisation fields for reflexes to individual
      muscles. Descending controls had a marked effect on the area from which
      sensitisation of flexor reflexes could be obtained, as the sensitisation fields
      for the flexor reflexes evoked from the toes were larger in spinalised compared
      to decerebrated, non-spinalised animals. The intermediate sizes of sensitisation
      fields in anaesthetised animals suggests that the area of these fields can be
      dynamically controlled from the brain. On the other hand, the sensitisation field
      for the heel-MG reflex varied little between preparations and appears to be a
      function of spinal neurones.

PMID- 12509494
TI  - Effects of leptin on cat intestinal motility.
AB  - In a previous study, we established that leptin controls food intake and immune
      responses by acting on intestinal vagal chemosensitive mechanoreceptors via a
      functional link with interleukin-1 beta (Il-1 beta). Since the control of
      intestinal motility is one of the main roles of the vagal afferent fibres, we
      investigated the effects of leptin on intestinal electromyographic (EMG) activity
      which reflects intestinal motility. For this purpose, the effects of locally
      injected leptin on small intestine spontaneous EMG activity were studied in 23
      anaesthetised cats. The EMG activity was recorded using bipolar electrodes
      implanted in the proximal small intestine. Leptin and Il-1 beta (0.1, 1 and 10
      microg), administered through the artery irrigating the upper part of the
      intestine 20 min after cholecystokinin (CCK, 10 microg, I.A.), had significant (P
      < 0.001) excitatory effects on intestinal EMG activity. The effects of both
      substances were blocked by the endogenous interleukin-1 beta receptor antagonist
      (Il-1ra, 250 microg, I.A.), by atropine (250 microg, I.A.) and by vagotomy. In
      the absence of CCK, leptin and Il-1 beta had no effect on intestinal electrical
      activity. It can therefore be concluded that: (1) leptin is effective only after
      the previous intervention of CCK, (2) the enhancement of the electrical activity
      induced by leptin involves Il-1 beta receptors and the cholinergic excitatory
      pathway, (3) the modes whereby the leptin-induced enhancement of EMG activity
      occurs strongly suggest that these effects are due to a long-loop reflex
      involving intestinal vagal afferent fibres and the parasympathetic nervous
      system.

PMID- 12509495
TI  - Effects of continuous positive airway pressure on upper airway inspiratory
      dynamics in awake patients with sleep-disordered breathing.
AB  - Continuous positive airway pressure (CPAP) is the main treatment of the
      obstructive sleep apnoea syndrome (OSAS). We assessed its effects on the upper
      airway (UA) dynamics in response to bilateral anterior magnetic phrenic nerve
      stimulation (BAMPS) in 17 awake untreated OSAS patients (15 males; 52 +/- 7
      years) whose effective CPAP (P(eff)) had been determined beforehand by a
      conventional titration sleep study. All twitch-related inspirations were flow
      limited, flow first rising to a maximum (V(Imax)), then decreasing to a minimum
      (V(Imin)), and then increasing again (M-shaped pattern). Up to V(Imin), the
      relationship between driving pressure (P(d)) and flow (V) could adequately be
      fitted to a polynomial regression model (V = k(1)P(d) + k(2)P(d)(2); r(2) = 0.71
      0.98, P < 0.0001). At atmospheric pressure V(Imax) was 700 +/- 377 ml s(-1),
      V(Imin) was 458 +/- 306 ml s(-1), k(1) was 154.5 +/- 63.9 ml s(-1) (cmH(2)O)(-1),
      and k(2) was 10.7 +/- 7.3 ml s(-1) (cmH(2)O)(-1). CPAP significantly increased
      V(Imax) and V(Imin) (peak values 1007 +/- 332 ml and 837 +/- 264 ml s(-1),
      respectively) as well as k(1) and k(2) (peak values 300.9 +/- 178.2 ml s(-1)
      (cmH(2)O)(-1) and 55.2 +/- 65.3 ml s(-1) (cmH(2)O)(-1), respectively). With
      increasing CPAP, k(1)/k(2) increased up to a peak value before decreasing. We
      defined as P(eff,stim) the CPAP value corresponding to the highest k(1)/k(2)
      value. P(eff,stim) was correlated with P(eff) (P(eff) = 7.0 +/- 2.0; P(eff,stim)
      = 6.4 +/- 2.6 cmH(2)O; r = 0.886; 95 % CI 0.696-0.960, P < 0.001). We conclude
      that CPAP improves UA dynamics in OSAS and that the therapeutic CPAP to apply can
      be predicted during wakefulness using BAMPS.

PMID- 12509496
TI  - Effects of ageing and regular aerobic exercise on endothelial fibrinolytic
      capacity in humans.
AB  - The capacity of the vascular endothelium locally to release tissue-type
      plasminogen activator (t-PA) is critical for effective endogenous fibrinolysis.
      We determined the influence of ageing and regular aerobic exercise on the net
      release of t-PA across the human forearm in vivo using both cross-sectional and
      intervention approaches. First, we studied 62 healthy men aged 22-35 or 50-75
      years of age who were either sedentary or endurance exercise-trained. Net
      endothelial release rates of t-PA were calculated as the product of the
      arteriovenous concentration gradient and forearm plasma flow to intra-arterial
      bradykinin and sodium nitroprusside. Second, we studied 10 older (60 +/- 2 years)
      healthy sedentary men before and after a 3 month aerobic exercise intervention.
      Net endothelial t-PA release was significantly blunted with age in the sedentary
      men. At the highest dose of bradykinin the increase in t-PA antigen release was
      approximately 35 % less (P < 0.05) in the older (from -1.0 +/- 0.4 to 37.8 +/-
      3.8 ng (100 ml tissue)(-1) min(-1)) compared with young (from 0.1 +/- 0.6 to 56.6
      +/- 9.2 ng (100 ml tissue)(-1) min(-1)) men. In contrast, the endurance-trained
      men did not demonstrate an age-related decline in the net release of t-PA
      antigen. After the exercise intervention, the capacity of the endothelium to
      release t-PA increased approximately 55 % (P < 0.05) to levels similar to those
      of the young adults and older endurance-trained men. Regulated endothelial t-PA
      release declines with age in sedentary men. Regular aerobic exercise may not only
      prevent, but could also reverse the age-related loss in endothelial fibrinolytic
      function.

PMID- 12509497
TI  - The effect of graded exercise on IL-6 release and glucose uptake in human
      skeletal muscle.
AB  - In this study, the hypothesis that the release of interleukin (IL)-6 from human
      muscle is linked to exercise intensity and muscle glucose uptake was
      investigated. In the overnight fasted state, seven healthy males performed knee
      extension exercise, kicking with both legs, each at 25 % of maximal power
      (W(max)) for 45 min (eliciting 23 +/- 1 % of pulmonary maximal oxygen uptake,
      V(O2,max)) and then simultaneously with one leg at 65 % and the other leg at 85 %
      W(max) for 35 min (40 +/- 1 % of pulmonary V(O2,max)). Blood was sampled from a
      femoral artery and both femoral veins, and blood flow was determined by
      thermodilution. Thigh plasma flow (0.15 +/- 0.01, 1.4 +/- 0.2, 2.0 +/- 0.1 and
      2.3 +/- 0.2 l min(-1) thigh(-1) at rest and 25 %, 65 % and 85 % W(max),
      respectively) and thigh oxygen uptake (0.02 +/- 0.01, 0.27 +/- 0.03, 0.48 +/-
      0.04 and 0.55 +/- 0.05 l min(-1) thigh(-1) at rest and 25 %, 65 % and 85 %
      W(max), respectively) increased with increasing exercise intensity (P < 0.05).
      Also, thigh IL-6 release (0.4 +/- 0.1, 1.3 +/- 0.5, 1.5 +/- 0.6 and 2.5 +/- 0.7
      ng min(-1) thigh(-1) at rest and 25 %, 65 % and 85 % W(max), respectively) and
      thigh glucose uptake (0.05 +/- 0.01, 0.3 +/- 0.05, 0.75 +/- 0.16, 1.07 +/- 0.15
      mmol min(-1) thigh(-1) at rest and 25 %, 65 % and 85 % W(max), respectively)
      increased with increasing exercise intensity (P < 0.05). During the last 35 min
      of exercise, arterial catecholamine concentrations were higher (P < 0.05) than at
      rest and during low-intensity exercise. During exercise, thigh IL-6 release was
      positively related to both thigh glucose uptake (P < 0.001) and thigh glucose
      delivery (P < 0.005), but not to thigh glucose extraction. Thigh IL-6 release was
      also positively related to arterial plasma adrenaline concentration. The pre
      exercise muscle glycogen concentration tended to correlate with the arteriovenous
      IL-6 concentration difference at rest, and the postexercise glycogen
      concentration was inversely correlated with IL-6 release during the final 35 min
      of exercise. In conclusion, the study indicates that IL-6 release from human
      muscle is positively related to exercise intensity, arterial adrenaline
      concentration and muscle glucose uptake. This supports the hypothesis that IL-6
      may be linked to the regulation of glucose homeostasis during exercise. The
      observation of a relationship between IL-6 release and muscle glycogen store both
      at rest and after exercise suggests that IL-6 may act as a carbohydrate sensor.

PMID- 12509498
TI  - Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced
      skeletal muscle blood flow and oxygen uptake in humans.
AB  - Previous studies show that exercise-induced hyperaemia is unaffected by systemic
      inhibition of nitric oxide synthase (NOS) and it has been proposed that this may
      be due to compensation by other vasodilators. We studied the involvement of
      cytochrome P450 2C9 (CYP 2C9) in the regulation of skeletal muscle blood flow in
      humans and the interaction between CYP 2C9 and NOS. Seven males performed knee
      extensor exercise. Blood flow was measured by thermodilution and blood samples
      were drawn frequently from the femoral artery and vein at rest, during exercise
      and in recovery. The protocol was repeated three times on the same day. The first
      and the third protocols were controls, and in the second protocol either the CYP
      2C9 inhibitor sulfaphenazole alone, or sulfaphenazole in combination with the NOS
      inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) were infused. Compared with
      control there was no difference in blood flow at any time with sulfaphenazole
      infusion (P > 0.05) whereas with infusion of sulfaphenazole and L-NMMA, blood
      flow during exercise was 16 +/- 4 % lower than in control (9 min: 3.67 +/- 0.31
      vs. 4.29 +/- 0.20 l min(-1); P < 0.05). Oxygen uptake during exercise was 12 +/-
      3 % lower (9 min: 525 +/- 46 vs. 594 +/- 24 ml min(-1); P < 0.05) with co
      infusion of sulfaphenazole and L-NMMA, whereas oxygen uptake during
      sulfaphenazole infusion alone was not different from that of control (P > 0.05).
      The results demonstrate that CYP 2C9 plays an important role in the regulation of
      hyperaemia and oxygen uptake during exercise. Since inhibition of neither NOS nor
      CYP 2C9 alone affect skeletal muscle blood flow, an interaction between CYP 2C9
      and NOS appears to exist so that a CYP-dependent vasodilator mechanism takes over
      when NO production is compromised.

PMID- 12509499
TI  - The time course and direction of lower limb vascular conductance changes during
      voluntary and electrically evoked isometric exercise of the contralateral calf
      muscle in man.
AB  - This study aimed to clarify the direction and timing of the change of non-active
      lower limb vascular conductance at the onset of contralateral limb isometric
      exercise and to examine the mechanisms controlling this change. Fifteen human
      subjects performed 2 min of electrically evoked (Stim) or voluntary (Vol)
      ischaemic isometric calf plantar flexor exercise at 30 % maximum voluntary
      contraction (MVC). Blood pressure (BP) and heart rate were continuously recorded
      and blood flow in the non-active contralateral lower limb was recorded at 15 s
      intervals. In subsets of subjects the presence of inadvertent muscle contraction
      was monitored by calf muscle EMG and the effects of the sensation of electrical
      stimulation without muscle contraction (sham) were investigated. After 10-15 s
      conductance had increased significantly (P < 0.05) in Vol and Stim by a mean of
      15 and 12 %, respectively, whilst BP was unchanged. Following this initial
      increase conductance decreased progressively during Stim and Vol whilst blood
      pressure rose. No EMG activity was seen during either protocol. In the sham
      stimulation experiments where no contraction was evoked the conductance change at
      the onset of stimulation replicated that seen during Stim exercise. Increases in
      conductance were independent of central command and muscle force generation, were
      not activated in anticipation of exercise but could be activated secondarily to
      peripheral sensations associated with expected exercise. The explanation for our
      results might involve sympathetic withdrawal related to mental stress; however, a
      central pathway, which directly activates a vasodilator mechanism in passive calf
      muscle, remains a possibility.

PMID- 12509500
TI  - Proteomics gives insight into the regulatory function of chloroplast
      thioredoxins.
AB  - Thioredoxins are small multifunctional redox active proteins widely if not
      universally distributed among living organisms. In chloroplasts, two types of
      thioredoxins (f and m) coexist and play central roles in regulating enzyme
      activity. Reduction of thioredoxins in chloroplasts is catalyzed by an iron
      sulfur disulfide enzyme, ferredoxin-thioredoxin reductase, that receives
      photosynthetic electrons from ferredoxin, thereby providing a link between light
      and enzyme activity. Chloroplast thioredoxins function in the regulation of the
      Calvin cycle and associated processes. However, the relatively small number of
      known thioredoxin-linked proteins (about 16) raised the possibility that others
      remain to be identified. To pursue this opportunity, we have mutated thioredoxins
      f and m, such that the buried cysteine of the active disulfide has been replaced
      by serine or alanine, and bound them to affinity columns to trap target proteins
      of chloroplast stroma. The covalently linked proteins were eluted with DTT,
      separated on gels, and identified by mass spectrometry. This approach led to the
      identification of 15 potential targets that function in 10 chloroplast processes
      not known to be thioredoxin linked. Included are proteins that seem to function
      in plastid-to-nucleus signaling and in a previously unrecognized type of
      oxidative regulation. Approximately two-thirds of these targets contained
      conserved cysteines. We also identified 11 previously unknown and 9 confirmed
      target proteins that are members of pathways known to be regulated by
      thioredoxin. In contrast to results with individual enzyme assays, specificity
      for thioredoxin f or m was not observed on affinity chromatography.

PMID- 12509501
TI  - RNA interference machinery regulates chromosome dynamics during mitosis and
      meiosis in fission yeast.
AB  - The regulation of higher-order chromosome structure is central to cell division
      and sexual reproduction. Heterochromatin assembly at the centromeres facilitates
      both kinetochore formation and sister chromatid cohesion, and the formation of
      specialized chromatin structures at telomeres serves to maintain the length of
      telomeric repeats, to suppress recombination, and to aid in formation of a
      bouquet-like structure that facilitates homologous chromosome pairing during
      meiosis. In fission yeast, genes encoding the Argonaute, Dicer, and RNA-dependent
      RNA polymerase factors involved in RNA interference (RNAi) are required for
      heterochromatin formation at the centromeres and mating type region. In this
      study, we examine the effects of deletions of the fission yeast RNAi machinery on
      chromosome dynamics during mitosis and meiosis. We find that the RNAi machinery
      is required for the accurate segregation of chromosomes. Defects in mitotic
      chromosome segregation are correlated with loss of cohesin at centromeres.
      Although the telomeres of RNAi mutants maintain silencing, length, and
      localization of the heterochromatin protein Swi6, we discovered defects in the
      proper clustering of telomeres in interphase mitotic cells. Furthermore, a small
      proportion of RNAi mutant cells display aberrant telomere clustering during
      meiotic prophase. This study demonstrates that the fission yeast RNAi machinery
      is required for the proper regulation of chromosome architecture during mitosis
      and meiosis.

PMID- 12509502
TI  - Trypanosomatid transcription factors: waiting for Godot.

PMID- 12509503
TI  - Role of ABC transporters in secretion of cholesterol from liver into bile.

PMID- 12509504
TI  - Block of Shaker potassium channels by external calcium ions.
AB  - We describe an interaction between external Ca(2+) ions and Shaker K channels
      that is important in the gating of the channels. The interaction was first
      detected as a partial block of inward K(+) current in elevated Ca(2+), beginning
      near -40 mV and becoming stronger at more negative voltage. Surprisingly, the
      time course of the block can be resolved as a rapid decay of inward current
      magnitude following a repolarizing step. The rapid decay of current is shown to
      be the result of channel block by using a two-pulse procedure that monitors the
      time course of gate closing. As a result of block, the decay of the tail current
      after repolarization is two to three times faster than gate closing. With
      physiological values for voltage and calcium concentration, block is readily
      detectable from tail time course, implying that it occurs as a normal concomitant
      of gate closing in Shaker. The slight voltage dependence of block from -60 to 
      100 mV suggests that Ca(2+) is bound (with low affinity) near the outer mouth of
      the channel. Elevated calcium quickens the inward gating current recorded as
      Shaker channels are closing; this current approximately doubles in amplitude and
      has a faster time course and quicker rising phase. When combined, the results
      suggest that calcium accelerates the first step in closing of the channel gate,
      perhaps by changing the channel's ion-occupancy state.

PMID- 12509505
TI  - Canonical histidine kinase activity of the transmitter domain of the ETR1
      ethylene receptor from Arabidopsis is not required for signal transmission.
AB  - Ethylene signaling in plants is mediated by a family of receptors related to
      bacterial two-component histidine kinases. Of the five members of the Arabidopsis
      ethylene receptor family, members of subfamily I (ETR1 and ERS1) contain
      completely conserved histidine kinase domains, whereas members of subfamily II
      (ETR2, EIN4, and ERS2) lack conserved residues thought to be necessary for kinase
      activity. To examine the role of the conserved histidine kinase domain in
      receptor signaling, ers1;etr1 loss-of-function double mutants were generated. The
      double mutants exhibited a severe constitutive ethylene response phenotype
      consistent with the negative regulator model for receptor function. The adult
      ers1-2;etr1-6 and ers1-2;etr1-7 phenotypes included miniature rosette size,
      delayed flowering, and both male and female sterility, whereas etiolated-seedling
      responses were less affected. Chimeric transgene constructs in which the ETR1
      promoter was used to drive expression of cDNAs for each of the five receptor
      isoforms were transferred into the ers1-2;etr1-7 double-mutant plants. Subfamily
      I constructs restored normal growth, whereas subfamily II constructs failed to
      rescue the double mutant, providing evidence for a unique role for subfamily I in
      receptor signaling. However, transformation of either the ers1-2;etr1-6 or ers1
      2;etr1-7 mutant with a kinase-inactivated ETR1 genomic clone also resulted in
      complete restoration of normal growth and ethylene responsiveness in the double
      mutant background, leading to the conclusion that canonical histidine kinase
      activity by receptors is not required for ethylene receptor signaling.

PMID- 12509506
TI  - Identification of bile acid precursors as endogenous ligands for the nuclear
      xenobiotic pregnane X receptor.
AB  - Sterol 27-hydroxylase (CYP27A1) is required for bile acid synthesis by both the
      classical and alternate pathways. Cyp27a1(-/-) mice exhibit a dramatic increase
      in the activity of cytochrome P450 3A (CYP3A), which catalyzes side-chain
      hydroxylations of bile acid intermediates, thereby facilitating their excretion
      in the bile and urine. We examine the role of the nuclear xenobiotic receptor PXR
      (pregnane X receptor) in this process. We demonstrate that expression of Cyp3a11
      and other established PXR target genes is increased in the Cyp27a1(-/-) mice.
      WhenCyp27a1(-/-) mice are fed a diet containing either cholic acid or
      chenodeoxycholic acid, expression of CYP7A1, which catalyzes the rate-limiting
      step in bile acid biosynthesis, is strongly suppressed. In parallel, the
      induction of Cyp3a11 observed in these mice is reversed, suggesting that bile
      acid intermediates serve as PXR activators. In support of this hypothesis, three
      potentially toxic sterols (7alpha-hydroxy-4-cholesten-3-one, 5beta-cholestan
      3alpha,7alpha,12alpha-triol, and 4-cholesten-3-one), including two that are known
      to accumulate in Cyp27a1(-/-) mice, are efficacious activators of mouse PXR. All
      three compounds are more potent activators of mouse PXR than of human PXR, which
      may explain in part why humans who lack functional CYP27A1 do not display a
      corresponding increase in CYP3A activity and are stricken with the disease
      cerebrotendinous xanthomatosis. Taken together, these results reveal the
      existence of a feedforward regulatory loop by which potentially toxic bile acid
      intermediates activate PXR and induce their own metabolism. In addition, this
      study demonstrates that animal models with alterations in gene expression can be
      used to identify endogenous ligands for orphan nuclear receptors.

PMID- 12509507
TI  - Polyglutamine fibrillogenesis: the pathway unfolds.

PMID- 12509508
TI  - Beta -Arrestin 1 down-regulation after insulin treatment is associated with
      supersensitization of beta 2 adrenergic receptor Galpha s signaling in 3T3-L1
      adipocytes.
AB  - beta-Arrestin 1 is required for internalization and mitogen-activated protein
      (MAP) kinase activation by the beta2 adrenergic receptor (beta2AR). Our previous
      studies have shown that chronic insulin treatment down-regulates cellular beta
      arrestin 1 levels, leading to a marked impairment in G protein-coupled receptor
      and insulin-like growth factor-1 receptor-mediated MAP kinase and mitogenic
      signaling. In this study, we show that chronic insulin-treated, beta-arrestin
      1depleted 3T3-L1 adipocytes display (i) increased isoproterenol-induced cAMP
      generation (53 +/- 38% at 1.5 min, 25 +/- 19% at 5 min, 63 +/- 14% at 30 min, and
      59 +/- 2% at 60 min), a Galpha(s)-associated pathway; (ii) impaired isoproterenol
      induced beta2AR internalization (reduced by 98 +/- 4%), which is required for MAP
      kinase signaling, a Galpha(i)-associated pathway; and (iii) increased beta
      arrestin 1 phosphorylation at Ser-412. Taken together, these findings represent a
      hitherto unknown mechanism (degradation and phosphorylation of beta-arrestin,
      whereby the activation of the insulin receptor, belonging to the family of
      receptor tyrosine kinases, causes supersensitization of Galpha(s)-associated
      signaling and inhibition of Galpha(i)-associated signaling by the beta2AR, a
      prototypical G protein-coupled receptor.

PMID- 12509509
TI  - Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts.
AB  - Cells progressing through the cell cycle must commit irreversibly to mitosis
      without slipping back to interphase before properly segregating their
      chromosomes. A mathematical model of cell-cycle progression in cell-free egg
      extracts from frog predicts that irreversible transitions into and out of mitosis
      are driven by hysteresis in the molecular control system. Hysteresis refers to
      toggle-like switching behavior in a dynamical system. In the mathematical model,
      the toggle switch is created by positive feedback in the phosphorylation
      reactions controlling the activity of Cdc2, a protein kinase bound to its
      regulatory subunit, cyclin B. To determine whether hysteresis underlies entry
      into and exit from mitosis in cell-free egg extracts, we tested three predictions
      of the Novak-Tyson model. (i) The minimal concentration of cyclin B necessary to
      drive an interphase extract into mitosis is distinctly higher than the minimal
      concentration necessary to hold a mitotic extract in mitosis, evidence for
      hysteresis. (ii) Unreplicated DNA elevates the cyclin threshold for Cdc2
      activation, indication that checkpoints operate by enlarging the hysteresis loop.
      (iii) A dramatic "slowing down" in the rate of Cdc2 activation is detected at
      concentrations of cyclin B marginally above the activation threshold. All three
      predictions were validated. These observations confirm hysteresis as the driving
      force for cell-cycle transitions into and out of mitosis.

PMID- 12509510
TI  - Optimal alignment for enzymatic proton transfer: structure of the Michaelis
      complex of triosephosphate isomerase at 1.2-A resolution.
AB  - In enzyme catalysis, where exquisitely positioned functionality is the sine qua
      non, atomic coordinates for a Michaelis complex can provide powerful insights
      into activation of the substrate. We focus here on the initial proton transfer of
      the isomerization reaction catalyzed by triosephosphate isomerase and present the
      crystal structure of its Michaelis complex with the substrate dihydroxyacetone
      phosphate at near-atomic resolution. The active site is highly compact, with
      unusually short and bifurcated hydrogen bonds for both catalytic Glu-165 and His
      95 residues. The carboxylate oxygen of the catalytic base Glu-165 is positioned
      in an unprecedented close interaction with the ketone and the alpha-hydroxy
      carbons of the substrate (C em leader O approximately 3.0 A), which is optimal
      for the proton transfer involving these centers. The electrophile that polarizes
      the substrate, His-95, has close contacts to the substrate's O1 and O2 (N em
      leader O < or = 3.0 and 2.6 A, respectively). The substrate is conformationally
      relaxed in the Michaelis complex: the phosphate group is out of the plane of the
      ketone group, and the hydroxy and ketone oxygen atoms are not in the cisoid
      configuration. The epsilon ammonium group of the electrophilic Lys-12 is within
      hydrogen-bonding distance of the substrate's ketone oxygen, the bridging oxygen,
      and a terminal phosphate's oxygen, suggesting a role for this residue in both
      catalysis and in controlling the flexibility of active-site loop.

PMID- 12509511
TI  - Natural selection shaped regional mtDNA variation in humans.
AB  - Human mtDNA shows striking regional variation, traditionally attributed to
      genetic drift. However, it is not easy to account for the fact that only two
      mtDNA lineages (M and N) left Africa to colonize Eurasia and that lineages A, C,
      D, and G show a 5-fold enrichment from central Asia to Siberia. As an alternative
      to drift, natural selection might have enriched for certain mtDNA lineages as
      people migrated north into colder climates. To test this hypothesis we analyzed
      104 complete mtDNA sequences from all global regions and lineages. African mtDNA
      variation did not significantly deviate from the standard neutral model, but
      European, Asian, and Siberian plus Native American variations did. Analysis of
      amino acid substitution mutations (nonsynonymous, Ka) versus neutral mutations
      (synonymous, Ks) (kaks) for all 13 mtDNA protein-coding genes revealed that the
      ATP6 gene had the highest amino acid sequence variation of any human mtDNA gene,
      even though ATP6 is one of the more conserved mtDNA proteins. Comparison of the
      kaks ratios for each mtDNA gene from the tropical, temperate, and arctic zones
      revealed that ATP6 was highly variable in the mtDNAs from the arctic zone,
      cytochrome b was particularly variable in the temperate zone, and cytochrome
      oxidase I was notably more variable in the tropics. Moreover, multiple amino acid
      changes found in ATP6, cytochrome b, and cytochrome oxidase I appeared to be
      functionally significant. From these analyses we conclude that selection may have
      played a role in shaping human regional mtDNA variation and that one of the
      selective influences was climate.

PMID- 12509512
TI  - Genetically engineered stem rust resistance in barley using the Rpg1 gene.
AB  - The stem-rust-susceptible barley cv. Golden Promise was transformed by
      Agrobacterium-mediated transformation of immature zygotic embryos with the Rpg1
      genomic clone of cv. Morex containing a 520-bp 5' promoter region, 4,919-bp gene
      region, and 547-bp 3' nontranscribed sequence. Representatives of 42 transgenic
      barley lines obtained were characterized for their seedling infection response to
      pathotype Pgt-MCC of the stem rust fungus Puccinia graminis f. sp. tritici.
      Golden Promise was converted from a highly susceptible cultivar into a highly
      resistant one by transformation with the dominant Rpg1 gene. A single copy of the
      gene was sufficient to confer resistance against stem rust, and progenies from
      several transformants segregated in a 3:1 ratio for resistancesusceptibility as
      expected for Mendelian inheritance. These results unequivocally demonstrate that
      the DNA segment isolated by map-based cloning is the functional Rpg1 gene for
      stem rust, resistance. One of the remarkable aspects about the transformants is
      that they exhibit a higher level of resistance than the original sources of Rpg1
      (cvs. Chevron and Peatland). In most cases, the Golden Promise transformants
      exhibited a highly resistant reaction where no visible sign of infection was
      evident. Hypersensitive necrotic "fleck" reactions were also observed, but less
      frequently. With both infection types, pathogen sporulation was prevented.
      Southern blot and RT-PCR analysis revealed that neither Rpg1 gene copy number nor
      expression levels could account for the increased resistance observed in Golden
      Promise transformants. Nevertheless, this research demonstrates that stem-rust
      susceptible barley can be made resistant by transformation with the cloned Rpg1
      gene.

PMID- 12509513
TI  - Quantum-mechanical calculations of the stabilities of fluxional isomers of
      C4H(7)(+) in solution.
AB  - Although numerous quantum calculations have been made over the years of the
      stabilities of the fluxional isomers of C(4)H(7)(+), none have been reported for
      other than the gas phase (which is unrealistic for these ionic species) that
      exhibit exceptional fluxional properties in solution. To be sure, quantum
      mechanical calculations for solutions are subject to substantial uncertainties,
      but nonetheless it is important to see whether the trends seen for the gas-phase
      C(4)H(7)(+) species are also found in calculations for polar solutions. Of the
      C(4)H(7)(+) species, commonly designated bisected-cyclopropylcarbinyl 1, unsym
      bicyclobutonium 2, sym-bicyclobutonium 3, allylcarbinyl 4, and pyramidal
      structure 6, the most advanced gas-phase calculations available thus far suggest
      that the order of stability is 1 > or = 2 > or = 3 4 6 with barriers of only
      approximately 1 kcalmol for interconversions among 1, 2, and 3. We report here
      that, when account is taken of solvation, 2 turns out to be slightly more stable
      than 1 or 3 in polar solvents. The pattern of the overall results is unexpected,
      in that despite substantial differences in structures and charge distributions
      between the primary players in the C(4)H(7)(+) equilibria and the large
      differences in solvation energies calculated for the solvents considered, the
      differential solvent effects from species to species are rather small.

PMID- 12509514
TI  - Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II
      correlates with intensified fear-induced conflict behavior.
AB  - Behavioral reactions to stress are altered in numerous psychiatric and
      neurodegenerative syndromes, but the corresponding molecular processes and signal
      transduction pathways are yet unknown. Here, we report that, in mice, the stress
      induced splice variant of acetylcholinesterase, AChE-R, interacts intraneuronally
      with the scaffold protein RACK1 and through it, with its target, protein kinase
      CbetaII (PKCbetaII), which is known to be involved in fear conditioning. In
      stress-responsive brain regions of normal FVBN mice, the mild stress of i.p.
      injection increased AChE and PKCbetaII levels in a manner suppressible by
      antisense prevention of AChE-R accumulation. Injection stress also prolonged
      conflict between escape and hiding in the emergence into an open field test.
      Moreover, transgenic FVBN mice overexpressing AChE-R displayed prolonged delay to
      emerge into another field (fear-induced behavioral inhibition), associated with
      chronically intensified neuronal colabeling of RACK1 and PKCbetaII in stress
      responsive brain regions. These findings are consistent with the hypothesis that
      stress-associated changes in cholinergic gene expression regulate neuronal
      PKCbetaII functioning, promoting fear-induced conflict behavior after stress.

PMID- 12509515
TI  - Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal
      cholesterol metabolism and glucose-induced insulin secretion.
AB  - A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays
      an essential role in bone accrual and eye development. Here, we show that LRP5 is
      also required for normal cholesterol and glucose metabolism. The production of
      mice lacking LRP5 revealed that LRP5 deficiency led to increased plasma
      cholesterol levels in mice fed a high-fat diet, because of the decreased hepatic
      clearance of chylomicron remnants. In addition, when fed a normal diet, LRP5
      deficient mice showed a markedly impaired glucose tolerance. The LRP5-deficient
      islets had a marked reduction in the levels of intracellular ATP and Ca(2+) in
      response to glucose, and thereby glucose-induced insulin secretion was decreased.
      The intracellular inositol 1,4,5-trisphosphate (IP3) production in response to
      glucose was also reduced in LRP5-- islets. Real-time PCR analysis revealed a
      marked reduction of various transcripts for genes involved in glucose sensing in
      LRP5-- islets. Furthermore, exposure of LRP5++ islets to Wnt-3a and Wnt-5a
      stimulates glucose-induced insulin secretion and this stimulation was blocked by
      the addition of a soluble form of Wnt receptor, secreted Frizzled-related protein
      1. In contrast, LRP5-deficient islets lacked the Wnt-3a-stimulated insulin
      secretion. These data suggest that WntLRP5 signaling contributes to the glucose
      induced insulin secretion in the islets.

PMID- 12509516
TI  - Color and genomic ancestry in Brazilians.
AB  - This work was undertaken to ascertain to what degree the physical appearance of a
      Brazilian individual was predictive of genomic African ancestry. Using a panel of
      10 population-specific alleles, we assigned to each person an African ancestry
      index (AAI). The procedure was able to tell apart, with no overlaps, 20 males
      from northern Portugal from 20 males from Sao Tome Island on the west coast of
      Africa. We also tested 10 Brazilian Amerindians and observed that their AAI
      values fell in the same range as the Europeans. Finally, we studied two different
      Brazilian population samples. The first consisted of 173 individuals from a rural
      Southeastern community, clinically classified according to their Color (white,
      black, or intermediate) with a multivariate evaluation based on skin pigmentation
      in the medial part of the arm, hair color and texture, and the shape of the nose
      and lips. In contrast to the clear-cut results with the African and European
      samples, our results showed large variances and extensive overlaps among the
      three Color categories. We next embarked on a study of 200 unrelated Brazilian
      white males who originated from cosmopolitan centers of the four major geographic
      regions of the country. The results showed AAI values intermediate between
      Europeans and Africans, even in southern Brazil, a region predominantly peopled
      by European immigrants. Our data suggest that in Brazil, at an individual level,
      color, as determined by physical evaluation, is a poor predictor of genomic
      African ancestry, estimated by molecular markers.

PMID- 12509517
TI  - ATM to the rescue: repairing DNA damage.

PMID- 12509518
TI  - LEAFY COTYLEDON1-LIKE defines a class of regulators essential for embryo
      development.
AB  - Arabidopsis LEAFY COTYLEDON1 (LEC1) is a critical regulator required for normal
      development during the early and late phases of embryogenesis that is sufficient
      to induce embryonic development in vegetative cells. LEC1 encodes a HAP3 subunit
      of the CCAAT binding transcription factor. We show that the 10 Arabidopsis HAP3
      (AHAP3) subunits can be divided into two classes based on sequence identity in
      their central, conserved B domain. LEC1 and its most closely related subunit,
      LEC1-LIKE (L1L), constitute LEC1-type AHAP3 subunits, whereas the remaining AHAP3
      subunits are designated non-LEC1-type. Similar to LEC1, L1L is expressed
      primarily during seed development. However, suppression of L1L gene expression
      induced defects in embryo development that differed from those of lec1 mutants,
      suggesting that LEC1 and L1L play unique roles in embryogenesis. We show that L1L
      expressed under the control of DNA sequences flanking the LEC1 gene suppressed
      genetically the lec1 mutation, suggesting that the LEC1-type B domains of L1L and
      LEC1 are critical for their function in embryogenesis. Our results also suggest
      that LEC1-type HAP3 subunits arose from a common origin uniquely in plants. Thus,
      L1L, an essential regulator of embryo development, defines a unique class of
      plant HAP3 subunits.

PMID- 12509519
TI  - The Arabidopsis SOS5 locus encodes a putative cell surface adhesion protein and
      is required for normal cell expansion.
AB  - Cell surface proteoglycans have been implicated in many aspects of plant growth
      and development, but genetic evidence supporting their function has been lacking.
      Here, we report that the Salt Overly Sensitive5 (SOS5) gene encodes a putative
      cell surface adhesion protein and is required for normal cell expansion. The sos5
      mutant was isolated in a screen for Arabidopsis salt-hypersensitive mutants.
      Under salt stress, the root tips of sos5 mutant plants swell and root growth is
      arrested. The root-swelling phenotype is caused by abnormal expansion of
      epidermal, cortical, and endodermal cells. The SOS5 gene was isolated through map
      based cloning. The predicted SOS5 protein contains an N-terminal signal sequence
      for plasma membrane localization, two arabinogalactan protein-like domains, two
      fasciclin-like domains, and a C-terminal glycosylphosphatidylinositol lipid
      anchor signal sequence. The presence of fasciclin-like domains, which typically
      are found in animal cell adhesion proteins, suggests a role for SOS5 in cell-to
      cell adhesion in plants. The SOS5 protein was present at the outer surface of the
      plasma membrane. The cell walls are thinner in the sos5 mutant, and those between
      neighboring epidermal and cortical cells in sos5 roots appear less organized.
      SOS5 is expressed ubiquitously in all plant organs and tissues, including guard
      cells in the leaf.

PMID- 12509520
TI  - Enhanced transcription of the Arabidopsis disease resistance genes RPW8.1 and
      RPW8.2 via a salicylic acid-dependent amplification circuit is required for
      hypersensitive cell death.
AB  - The Arabidopsis disease resistance (R) genes RPW8.1 and RPW8.2 couple the
      recognition of powdery mildew pathogens of this plant with the subsequent
      induction of a localized necrosis, or hypersensitive response (HR). The HR
      restricts the spread of the infection and renders the plant resistant. One-third
      of Arabidopsis plants transformed with a genomic fragment containing RPW8.1 and
      RPW8.2 developed spontaneous HR-like lesions (SHL) in the absence of pathogens.
      We demonstrate that SHL occurs in transgenic lines that contain multiple copies
      of the transgene and express RPW8.1 and RPW8.2 at high levels. SHL is associated
      with salicylic acid (SA) accumulation, and at the site of the lesion, there is
      increased expression of RPW8.1, increased production of H(2)O(2), and increased
      expression of pathogenesis-related genes. These lesions are physiologically
      similar to the pathogen-induced HR mediated by RPW8.1 and RPW8.2. Significantly,
      environmental conditions that suppress SHL suppress the transcription of RPW8.1
      and RPW8.2 and also suppress resistance to powdery mildews, even in transgenic
      lines containing RPW8.1 and RPW8.2 that normally do not express SHL. Furthermore,
      treatment with SA increases the transcription of RPW8.1 and RPW8.2, induces SHL,
      and enhances resistance to powdery mildews. We conclude that HR requires the
      transcription of RPW8.1 and RPW8.2, which is regulated independently of the
      pathogen by SA-dependent feedback amplification.

PMID- 12509521
TI  - Oxidative remodeling of chromoplast carotenoids: identification of the carotenoid
      dioxygenase CsCCD and CsZCD genes involved in Crocus secondary metabolite
      biogenesis.
AB  - The accumulation of three major carotenoid derivatives-crocetin glycosides,
      picrocrocin, and safranal-is in large part responsible for the color, bitter
      taste, and aroma of saffron, which is obtained from the dried styles of Crocus.
      We have identified and functionally characterized the Crocus zeaxanthin
      7,8(7',8')-cleavage dioxygenase gene (CsZCD), which codes for a chromoplast
      enzyme that initiates the biogenesis of these derivatives. The Crocus carotenoid
      9,10(9',10')-cleavage dioxygenase gene (CsCCD) also has been cloned, and the
      comparison of substrate specificities between these two enzymes has shown that
      the CsCCD enzyme acts on a broader range of precursors. CsZCD expression is
      restricted to the style branch tissues and is enhanced under dehydration stress,
      whereas CsCCD is expressed constitutively in flower and leaf tissues irrespective
      of dehydration stress. Electron microscopy revealed that the accumulation of
      saffron metabolites is accompanied by the differentiation of amyloplasts and
      chromoplasts and by interactions between chromoplasts and the vacuole. Our data
      suggest that a stepwise sequence exists that involves the oxidative cleavage of
      zeaxanthin in chromoplasts followed by the sequestration of modified water
      soluble derivatives into the central vacuole.

PMID- 12509522
TI  - Arabidopsis AtMYC2 (bHLH) and AtMYB2 (MYB) function as transcriptional activators
      in abscisic acid signaling.
AB  - In Arabidopsis, the induction of a dehydration-responsive gene, rd22, is mediated
      by abscisic acid (ABA). We reported previously that MYC and MYB recognition sites
      in the rd22 promoter region function as cis-acting elements in the drought- and
      ABA-induced gene expression of rd22. bHLH- and MYB-related transcription factors,
      rd22BP1 (renamed AtMYC2) and AtMYB2, interact specifically with the MYC and MYB
      recognition sites, respectively, in vitro and activate the transcription of the
      beta-glucuronidase reporter gene driven by the MYC and MYB recognition sites in
      Arabidopsis leaf protoplasts. Here, we show that transgenic plants overexpressing
      AtMYC2 and/or AtMYB2 cDNAs have higher sensitivity to ABA. The ABA-induced gene
      expression of rd22 and AtADH1 was enhanced in these transgenic plants. Microarray
      analysis of the transgenic plants overexpressing both AtMYC2 and AtMYB2 cDNAs
      revealed that several ABA-inducible genes also are upregulated in the transgenic
      plants. By contrast, a Ds insertion mutant of the AtMYC2 gene was less sensitive
      to ABA and showed significantly decreased ABA-induced gene expression of rd22 and
      AtADH1. These results indicate that both AtMYC2 and AtMYB2 proteins function as
      transcriptional activators in ABA-inducible gene expression under drought stress
      in plants.

PMID- 12509523
TI  - Altered cell cycle distribution, hyperplasia, and inhibited differentiation in
      Arabidopsis caused by the D-type cyclin CYCD3.
AB  - CYCD3;1 expression in Arabidopsis is associated with proliferating tissues such
      as meristems and developing leaves but not with differentiated tissues.
      Constitutive overexpression of CYCD3;1 increases CYCD3;1-associated kinase
      activity and reduces the proportion of cells in the G1-phase of the cell cycle.
      Moreover, CYCD3;1 overexpression leads to striking alterations in development.
      Leaf architecture in overexpressing plants is altered radically, with a failure
      to develop distinct spongy and palisade mesophyll layers. Associated with this,
      we observe hyperproliferation of leaf cells; in particular, the epidermis
      consists of large numbers of small, incompletely differentiated polygonal cells.
      Endoreduplication, a marker for differentiated cells that have exited from the
      mitotic cell cycle, is inhibited strongly in CYCD3;1-overexpressing plants.
      Transcript analysis reveals an activation of putative compensatory mechanisms
      upon CYCD3;1 overexpression or subsequent cell cycle activation. These results
      demonstrate that cell cycle exit in the G1-phase is required for normal cellular
      differentiation processes during plant development and suggest a critical role
      for CYCD3 in the switch from cell proliferation to the final stages of
      differentiation.

PMID- 12509524
TI  - Tandemly duplicated Arabidopsis genes that encode polygalacturonase-inhibiting
      proteins are regulated coordinately by different signal transduction pathways in
      response to fungal infection.
AB  - Polygalacturonase-inhibiting proteins (PGIPs) are plant proteins that counteract
      fungal polygalacturonases, which are important virulence factors. Like many other
      plant defense proteins, PGIPs are encoded by gene families, but the roles of
      individual genes in these families are poorly understood. Here, we show that in
      Arabidopsis, two tandemly duplicated PGIP genes are upregulated coordinately in
      response to Botrytis cinerea infection, but through separate signal transduction
      pathways. AtPGIP2 expression is mediated by jasmonate and requires COI1 and JAR1,
      whereas AtPGIP1 expression is upregulated strongly by oligogalacturonides but is
      unaffected by salicylic acid, jasmonate, or ethylene. Both AtPGIP1 and AtPGIP2
      encode functional inhibitors of polygalacturonase from Botrytis, and their
      overexpression in Arabidopsis significantly reduces Botrytis disease symptoms.
      Therefore, gene duplication followed by the divergence of promoter regions may
      result in different modes of regulation of similar defensive proteins, thereby
      enhancing the likelihood of defense gene activation during pathogen infection.

PMID- 12509525
TI  - The nitrate transporter AtNRT1.1 (CHL1) functions in stomatal opening and
      contributes to drought susceptibility in Arabidopsis.
AB  - The movement of guard cells in stomatal complexes controls water loss and CO(2)
      uptake in plants. Examination of the dual-affinity nitrate transporter gene
      AtNRT1.1 (CHL1) revealed that it is expressed and functions in Arabidopsis guard
      cells. CHL1 promoter-beta-glucuronidase and CHL1 promoter-green fluorescent
      protein constructs showed strong expression in guard cells, and
      immunolocalization experiments with anti-CHL1 antibody confirmed these results.
      To assess CHL1 function, chl1 mutant plants grown in the presence of nitrate were
      examined. Compared with wild-type plants, chl1 mutants had reduced stomatal
      opening and reduced transpiration rates in the light or when deprived of CO(2) in
      the dark. These effects result in enhanced drought tolerance in chl1 mutants. At
      the cellular level, chl1 mutants showed reduced nitrate accumulation in guard
      cells during stomatal opening and failed to show nitrate-induced depolarization
      of guard cells. In wild-type guard cells, nitrate induced depolarization, and
      nitrate concentrations increased threefold during stomatal opening. These results
      identify an anion transporter that functions in stomatal opening and demonstrate
      that CHL1 supports stomatal function in the presence of nitrate.

PMID- 12509526
TI  - AtATM is essential for meiosis and the somatic response to DNA damage in plants.
AB  - In contrast to yeast or mammalian cells, little is known about the signaling
      responses to DNA damage in plants. We previously characterized AtATM, an
      Arabidopsis homolog of the human ATM gene, which is mutated in ataxia
      telangiectasia, a chromosome instability disorder. The Atm protein is a protein
      kinase whose activity is induced by DNA damage, particularly DNA double-strand
      breaks. The phosphorylation targets of Atm include proteins involved in DNA
      repair, cell cycle control, and apoptosis. Here, we describe the isolation and
      functional characterization of two Arabidopsis mutants carrying a T-DNA insertion
      in AtATM. Arabidopsis atm mutants are hypersensitive to gamma-radiation and
      methylmethane sulfonate but not to UV-B light. In correlation with the radiation
      sensitivity, atm mutants failed to induce the transcription of genes involved in
      the repair and/or detection of DNA breaks upon irradiation. In addition, atm
      mutants are partially sterile, and we show that this effect is attributable to
      abundant chromosomal fragmentation during meiosis. Interestingly, the
      transcription of DNA recombination genes during meiosis was not dependent on
      AtATM, and meiotic recombination occurred at the same rate as in wild-type
      plants, raising questions about the function of AtAtm during meiosis in plants.
      Our results demonstrate that AtATM plays a central role in the response to both
      stress-induced and developmentally programmed DNA damage.

PMID- 12509527
TI  - Three isoforms of isoamylase contribute different catalytic properties for the
      debranching of potato glucans.
AB  - Isoamylases are debranching enzymes that hydrolyze alpha-1,6 linkages in alpha
      1,4/alpha-1,6-linked glucan polymers. In plants, they have been shown to be
      required for the normal synthesis of amylopectin, although the precise manner in
      which they influence starch synthesis is still debated. cDNA clones encoding
      three distinct isoamylase isoforms (Stisa1, Stisa2, and Stisa3) have been
      identified from potato. The expression patterns of the genes are consistent with
      the possibility that they all play roles in starch synthesis. Analysis of the
      predicted sequences of the proteins suggested that only Stisa1 and Stisa3 are
      likely to have hydrolytic activity and that there probably are differences in
      substrate specificity between these two isoforms. This was confirmed by the
      expression of each isoamylase in Escherichia coli and characterization of its
      activity. Partial purification of isoamylase activity from potato tubers showed
      that Stisa1 and Stisa2 are associated as a multimeric enzyme but that Stisa3 is
      not associated with this enzyme complex. Our data suggest that Stisa1 and Stisa2
      act together to debranch soluble glucan during starch synthesis. The catalytic
      specificity of Stisa3 is distinct from that of the multimeric enzyme, indicating
      that it may play a different role in starch metabolism.

PMID- 12509528
TI  - Overexpression of a novel class of gibberellin 2-oxidases decreases gibberellin
      levels and creates dwarf plants.
AB  - Degradation of active C(19)-gibberellins (GAs) by dioxygenases through 2beta
      hydroxylation yields inactive GA products. We identified two genes in Arabidopsis
      (AtGA2ox7 and AtGA2ox8), using an activation-tagging mutant screen, that encode
      2beta-hydroxylases. GA levels in both activation-tagged lines were reduced
      significantly, and the lines displayed dwarf phenotypes typical of mutants with a
      GA deficiency. Increased expression of either AtGA2ox7 or AtGA2ox8 also caused a
      dwarf phenotype in tobacco, indicating that the substrates for these enzymes are
      conserved. AtGA2ox7 and AtGA2ox8 are more similar to each other than to other
      proteins encoded in the Arabidopsis genome, indicating that they may constitute a
      separate class of GA-modifying enzymes. Indeed, enzymatic assays demonstrated
      that AtGA2ox7 and AtGA2ox8 both perform the same GA modification: 2beta
      hydroxylation of C(20)-GAs but not of C(19)-GAs. Lines containing increased
      expression of AtGA2ox8 exhibited a GA dose-response curve for stem elongation
      similar to that of the biosynthetic mutant ga1-11. Double loss-of-function
      Atga2ox7 Atga2ox8 mutants had twofold to fourfold higher levels of active GAs and
      displayed phenotypes associated with excess GAs, such as early bolting in short
      days, resistance to the GA biosynthesis inhibitor ancymidol, and decreased mRNA
      levels of AtGA20ox1, a gene in the GA biosynthetic pathway.

PMID- 12509529
TI  - ETHYLENE RESPONSE FACTOR1 integrates signals from ethylene and jasmonate pathways
      in plant defense.
AB  - Cross-talk between ethylene and jasmonate signaling pathways determines the
      activation of a set of defense responses against pathogens and herbivores.
      However, the molecular mechanisms that underlie this cross-talk are poorly
      understood. Here, we show that ethylene and jasmonate pathways converge in the
      transcriptional activation of ETHYLENE RESPONSE FACTOR1 (ERF1), which encodes a
      transcription factor that regulates the expression of pathogen response genes
      that prevent disease progression. The expression of ERF1 can be activated rapidly
      by ethylene or jasmonate and can be activated synergistically by both hormones.
      In addition, both signaling pathways are required simultaneously to activate
      ERF1, because mutations that block any of them prevent ERF1 induction by any of
      these hormones either alone or in combination. Furthermore, 35S:ERF1 expression
      can rescue the defense response defects of coi1 (coronative insensitive1) and
      ein2 (ethylene insensitive2); therefore, it is a likely downstream component of
      both ethylene and jasmonate signaling pathways. Transcriptome analysis in
      Col;35S:ERF1 transgenic plants and ethylene/jasmonate-treated wild-type plants
      further supports the notion that ERF1 regulates in vivo the expression of a large
      number of genes responsive to both ethylene and jasmonate. These results suggest
      that ERF1 acts downstream of the intersection between ethylene and jasmonate
      pathways and suggest that this transcription factor is a key element in the
      integration of both signals for the regulation of defense response genes.

PMID- 12509530
TI  - The Arabidopsis ref2 mutant is defective in the gene encoding CYP83A1 and shows
      both phenylpropanoid and glucosinolate phenotypes.
AB  - The Arabidopsis ref2 mutant was identified in a screen for plants having altered
      fluorescence under UV light. Characterization of the ref2 mutants showed that
      they contained reduced levels of a number of phenylpropanoid pathway-derived
      products: sinapoylmalate in leaves, sinapoylcholine in seeds, and syringyl lignin
      in stems. Surprisingly, positional cloning of the REF2 locus revealed that it
      encodes CYP83A1, a cytochrome P450 sharing a high degree of similarity to
      CYP83B1, an enzyme involved in glucosinolate biosynthesis. Upon further
      investigation, ref2 mutants were found to have reduced levels of all aliphatic
      glucosinolates and increased levels of indole-derived glucosinolates in their
      leaves. These results show that CYP83A1 is involved in the biosynthesis of both
      short-chain and long-chain aliphatic glucosinolates and suggest a novel metabolic
      link between glucosinolate biosynthesis, a secondary biosynthetic pathway found
      only in plants in the order Capparales, and phenylpropanoid metabolism, a pathway
      found in all plants and considered essential to the survival of terrestrial plant
      species.

PMID- 12509531
TI  - Unique architecture of the plastid ribosomal RNA operon promoter recognized by
      the multisubunit RNA polymerase in tobacco and other higher plants.
AB  - Expression of the plastid rRNA operon (rrn) during development is highly
      regulated at the level of transcription. The plastid rrn operon in most higher
      plants is transcribed by the plastid-encoded RNA polymerase (PEP), the
      multisubunit plastid RNA polymerase from PrrnP1, a sigma(70)-type promoter with
      conserved -10 and -35 core promoter elements. To identify functionally important
      sequences, the tobacco PrrnP1 was dissected in vivo and in vitro. Based on in
      vivo deletion analysis, sequences upstream of nucleotide -83 do not significantly
      contribute to promoter function. The in vitro analyses identified an essential
      hexameric sequence upstream of the -35 element (GTGGGA; the rRNA operon upstream
      activator [RUA]) that is conserved in monocot and dicot species and suggested
      that the -10 element plays only a limited role in PrrnP1 recognition. Mutations
      in the initial transcribed sequence (+9 to +14) enhanced transcription, the
      characteristic of strong promoters in prokaryotes. We propose that sigma
      interaction with the -10 element in PrrnP1 is replaced in part by direct PEP-RUA
      (protein-DNA) interaction or by protein-protein interaction between the PEP and
      an RUA binding transcription factor.

PMID- 12509532
TI  - Global identification of target genes regulated by APETALA3 and PISTILLATA floral
      homeotic gene action.
AB  - Identifying the genes regulated by the floral homeotic genes APETALA3 (AP3) and
      PISTILLATA (PI) is crucial for understanding the molecular mechanisms that lead
      to petal and stamen formation. We have used microarray analysis to conduct a
      broad survey of genes whose expression is affected by AP3 and PI activity. DNA
      microarrays consisting of 9216 Arabidopsis ESTs were screened with probes
      corresponding to mRNAs from different mutant and transgenic lines that misexpress
      AP3 and/or PI. The microarray results were further confirmed by RNA gel blot
      analyses. Our results suggest that AP3 and PI regulate a relatively small number
      of genes, implying that many genes used in petal and stamen development are not
      tissue specific and likely have roles in other processes as well. We recovered
      genes similar to previously identified petal- and stamen-expressed genes as well
      as genes that were not implicated previously in petal and stamen development. A
      very low percentage of the genes recovered encoded transcription factors. This
      finding suggests that AP3 and PI act relatively directly to regulate the genes
      required for the basic cellular processes responsible for petal and stamen
      morphogenesis.

PMID- 12509533
TI  - Dual role of TOC1 in the control of circadian and photomorphogenic responses in
      Arabidopsis.
AB  - To examine the role of the TOC1 (TIMING OF CAB EXPRESSION1) gene in the
      Arabidopsis circadian system, we generated a series of transgenic plants
      expressing a gradation in TOC1 levels. Silencing of the TOC1 gene causes
      arrhythmia in constant darkness and in various intensities of red light, whereas
      in blue light, the clock runs faster in silenced plants than in wild-type plants.
      Increments in TOC1 gene dosage delayed the pace of the clock, whereas TOC1
      overexpression abolished rhythmicity in all light conditions tested. Our results
      show that TOC1 RNA interference and toc1-2 mutant plants displayed an important
      reduction in sensitivity to red and far-red light in the control of hypocotyl
      elongation, whereas increments in TOC1 gene dosage clearly enhanced light
      sensitivity. Furthermore, the red light-mediated induction of CCA1/LHY expression
      was decreased in TOC1 RNA interference and toc1-2 mutant plants, indicating a
      role for TOC1 in the phytochrome regulation of circadian gene expression. We
      conclude that TOC1 is an important component of the circadian clock in
      Arabidopsis with a crucial function in the integration of light signals to
      control circadian and morphogenic responses.

PMID- 12509534
TI  - Actin-depolymerizing factor mediates Rac/Rop GTPase-regulated pollen tube growth.
AB  - Pollen tube elongation is a rapid tip growth process that is driven by a dynamic
      actin cytoskeleton. A ubiquitous family of actin binding proteins, actin
      depolymerizing factors (ADFs)/cofilins, bind to actin filaments, induce severing,
      enhance depolymerization from their slow-growing end, and are important for
      maintaining actin dynamics in vivo. ADFs/cofilins are regulated by multiple
      mechanisms, among which Rho small GTPase-activated phosphorylation at a terminal
      region Ser residue plays an important role in regulating their actin binding and
      depolymerizing activity, affecting actin reorganization. We have shown previously
      that a tobacco pollen-specific ADF, NtADF1, is important for maintaining normal
      pollen tube actin cytoskeleton organization and growth. Here, we show that
      tobacco pollen grains accumulate phosphorylated and nonphosphorylated forms of
      ADFs, suggesting that phosphorylation could be a regulatory mechanism for their
      activity. In plants, Rho-related Rac/Rop GTPases have been shown to be important
      regulators for pollen tube growth. Overexpression of Rac/Rop GTPases converts
      polar growth into isotropic growth, resulting in pollen tubes with ballooned tips
      and a disrupted actin cytoskeleton. Using the Rac/Rop GTPase-induced defective
      pollen tube phenotype as a functional assay, we show that overexpression of
      NtADF1 suppresses the ability of NtRac1, a tobacco Rac/Rop GTPase, to convert
      pollen tube tip growth to isotropic growth. This finding suggests that NtADF1
      acts in a common pathway with NtRac1 to regulate pollen tube growth. A mutant
      form of NtADF1 with a nonphosphorylatable Ala substitution at its Ser-6 position
      [NtADF1(S6A)] shows increased activity, whereas the mutant NtADF1(S6D), which has
      a phospho-mimicking Asp substitution at the same position, shows reduced ability
      to counteract the effect of NtRac1. These observations suggest that
      phosphorylation at Ser-6 of NtADF1 could be important for its integration into
      the NtRac1 signaling pathway. Moreover, overexpression of NtRac1 diminishes the
      actin binding activity of green fluorescent protein (GFP)-NtADF1 but has little
      effect on the association of GFP-NtADF1(S6A) with actin cables in pollen tubes.
      Together, these observations suggest that NtRac1-activated activity regulates the
      actin binding and depolymerizing activity of NtADF1, probably via phosphorylation
      at Ser-6. This notion is further supported by the observation that overexpressing
      a constitutively active NtRac1 in transformed pollen grains significantly
      increases the ratio of phosphorylated to nonphosphorylated ADFs. Together, the
      observations reported here strongly support the idea that NtRac1 modulates NtADF1
      activity through phosphorylation at Ser-6 to regulate actin dynamics.

PMID- 12509535
TI  - In vitro assays demonstrate that pollen tube organelles use kinesin-related motor
      proteins to move along microtubules.
AB  - The movement of pollen tube organelles relies on cytoskeletal elements. Although
      the movement of organelles along actin filaments in the pollen tube has been
      studied widely and is becoming progressively clear, it remains unclear what role
      microtubules play. Many uncertainties about the role of microtubules in the
      active transport of pollen tube organelles and/or in the control of this process
      remain to be resolved. In an effort to determine if organelles are capable of
      moving along microtubules in the absence of actin, we extracted organelles from
      tobacco pollen tubes and analyzed their ability to move along in vitro
      polymerized microtubules under different experimental conditions. Regardless of
      their size, the organelles moved at different rates along microtubules in the
      presence of ATP. Cytochalasin D did not inhibit organelle movement, indicating
      that actin filaments are not required for organelle transport in our assay. The
      movement of organelles was cytosol independent, which suggests that soluble
      factors are not necessary for the organelle movement to occur and that
      microtubule-based motor proteins are present on the organelle surface. By washing
      organelles with KI, it was possible to release proteins capable of gliding
      carboxylated beads along microtubules. Several membrane fractions, which were
      separated by Suc density gradient centrifugation, showed microtubule-based
      movement. Proteins were extracted by KI treatment from the most active organelle
      fraction and then analyzed with an ATP-sensitive microtubule binding assay.
      Proteins isolated by the selective binding to microtubules were tested for the
      ability to glide microtubules in the in vitro motility assay, for the presence of
      microtubule-stimulated ATPase activity, and for cross-reactivity with anti
      kinesin antibodies. We identified and characterized a 105-kD organelle-associated
      motor protein that is functionally, biochemically, and immunologically related to
      kinesin. This work provides clear evidence that the movement of pollen tube
      organelles is not just actin based; rather, they show a microtubule-based motion
      as well. This unexpected finding suggests new insights into the use of pollen
      tube microtubules, which could be used for short-range transport, as actin
      filaments are in animal cells.

PMID- 12509536
TI  - The transcription factors HvABI5 and HvVP1 are required for the abscisic acid
      induction of gene expression in barley aleurone cells.
AB  - The abscisic acid (ABA) response promoter complexes (ABRCs) of the HVA1 and HVA22
      genes have been shown to confer ABA-induced gene expression in cereals. A barley
      basic domain/Leu zipper (bZIP) transcription factor, HvABI5, is able to recognize
      ABRCs in vitro in a sequence-specific manner and to transactivate ABRC-beta
      glucuronidase reporter genes when introduced to barley aleurone cells via
      particle bombardment. This transactivation is dependent on the presence of
      another transcription factor, HvVP1, and cannot be blocked by the negative
      regulator abi1-1. Using the double-stranded RNA interference technique, we show
      that HvABI5 and HvVP1 are necessary for the ABA induction of gene expression but
      have no effect on another hormone-regulated process, the gibberellin-induced and
      ABA-suppressed expression of alpha-amylase. Our work indicates that although
      other typical plant bZIP transcription factors may bind ABRCs in vitro, HvABI5 is
      related to a subfamily of bZIPs responsible for the ABA induction of gene
      expression. Furthermore, HvABI5 and HvVP1 are not involved in the ABA suppression
      of gene expression.

PMID- 12509538
TI  - Welcoming the new year.

PMID- 12509537
TI  - Unstable F-actin specifies the area and microtubule direction of cell expansion
      in Arabidopsis root hairs.
AB  - Plant cells expand by exocytosis of wall material contained in Golgi-derived
      vesicles. We examined the role of local instability of the actin cytoskeleton in
      specifying the exocytosis site in Arabidopsis root hairs. During root hair
      growth, a specific actin cytoskeleton configuration is present in the cell's
      subapex, which consists of fine bundles of actin filaments that become more and
      more fine toward the apex, where they may be absent. Pulse application of low
      concentrations of the actin-depolymerizing drugs cytochalasin D and latrunculin A
      broadened growing root hair tips (i.e., they increased the area of cell
      expansion). Interestingly, recovery from cytochalasin D led to new growth in the
      original growth direction, whereas in the presence of oryzalin, a microtubule
      depolymerizing drug, this direction was altered. Oryzalin alone, at the same
      concentration, had no influence on root hair elongation. These results represent
      an important step toward understanding the spatial and directional regulation of
      root hair growth.

PMID- 12509539
TI  - Stimulation of preterm infants.

PMID- 12509540
TI  - What's new: proton pump inhibitors and pediatrics.

PMID- 12509541
TI  - Visual diagnosis: two infants who have coarse facial features and growth and
      developmental delay.

PMID- 12509542
TI  - Index of suspicion.

PMID- 12509543
TI  - The prenatal pediatric visit.

PMID- 12509544
TI  - Apnea.

PMID- 12509545
TI  - Inguinal hernia.

PMID- 12509546
TI  - The role of emergent neuroimaging in children with new-onset afebrile seizures.
AB  - OBJECTIVES: The objectives of this study were 1) to determine the frequency of
      clinically significant abnormal neuroimaging in children coming to the emergency
      department (ED) with new-onset afebrile seizures (ASZ), and 2) to identify
      children at high or low risk for clinically significant abnormal neuroimaging.
      DESIGN/METHODS: Five hundred consecutive cases of new-onset ASZ seen in the ED of
      a tertiary care children's hospital were reviewed. Neuroimaging reports were
      categorized as normal, clinically insignificant abnormal, or clinically
      significant abnormal. Recursive partition analysis was used to identify clinical
      variables that separated children into high- and low-risk groups for clinically
      significant abnormal neuroimaging. RESULTS: Ninety-five percent of patients
      (475/500) with new-onset ASZ had neuroimaging. Clinically significant abnormal
      neuroimaging was noted in 8% (95% confidence interval [CI]: 6, 11; 38/475) of
      patients. Recursive partition analysis identified 2 criteria associated with high
      risk for clinically significant abnormal neuroimaging: 1) the presence of a
      predisposing condition, and 2) focal seizure if <33 months old. Of the high-risk
      patients, 26% (95% CI: 17, 35; 32/121) had clinically significant abnormal
      neuroimaging compared with 2% (95% CI: 0.6, 3.7; 6/354) in the low-risk group.
      CONCLUSIONS: In this large, retrospective review of children with new-onset ASZ,
      clinically significant abnormal neuroimaging occurred with relatively low
      frequency. Emergent neuroimaging should be considered, however, for children who
      meet high-risk criteria. Well-appearing children who meet low-risk criteria can
      be safely discharged from the ED (if follow-up can be assured) without emergent
      neuroimaging, because their risk for clinically significant abnormal neuroimaging
      is appreciably lower.

PMID- 12509547
TI  - Errors in medical interpretation and their potential clinical consequences in
      pediatric encounters.
AB  - BACKGROUND: About 19 million people in the United States are limited in English
      proficiency, but little is known about the frequency and potential clinical
      consequences of errors in medical interpretation. OBJECTIVES: To determine the
      frequency, categories, and potential clinical consequences of errors in medical
      interpretation. METHODS: During a 7-month period, we audiotaped and transcribed
      pediatric encounters in a hospital outpatient clinic in which a Spanish
      interpreter was used. For each transcript, we categorized each error in medical
      interpretation and determined whether errors had a potential clinical
      consequence. RESULTS: Thirteen encounters yielded 474 pages of transcripts.
      Professional hospital interpreters were present for 6 encounters; ad hoc
      interpreters included nurses, social workers, and an 11-year-old sibling. Three
      hundred ninety-six interpreter errors were noted, with a mean of 31 per
      encounter. The most common error type was omission (52%), followed by false
      fluency (16%), substitution (13%), editorialization (10%), and addition (8%).
      Sixty-three percent of all errors had potential clinical consequences, with a
      mean of 19 per encounter. Errors committed by ad hoc interpreters were
      significantly more likely to be errors of potential clinical consequence than
      those committed by hospital interpreters (77% vs 53%). Errors of clinical
      consequence included: 1) omitting questions about drug allergies; 2) omitting
      instructions on the dose, frequency, and duration of antibiotics and rehydration
      fluids; 3) adding that hydrocortisone cream must be applied to the entire body,
      instead of only to facial rash; 4) instructing a mother not to answer personal
      questions; 5) omitting that a child was already swabbed for a stool culture; and
      6) instructing a mother to put amoxicillin in both ears for treatment of otitis
      media. CONCLUSIONS: Errors in medical interpretation are common, averaging 31 per
      clinical encounter, and omissions are the most frequent type. Most errors have
      potential clinical consequences, and those committed by ad hoc interpreters are
      significantly more likely to have potential clinical consequences than those
      committed by hospital interpreters. Because errors by ad hoc interpreters are
      more likely to have potential clinical consequences, third-party reimbursement
      for trained interpreter services should be considered for patients with limited
      English proficiency.

PMID- 12509548
TI  - To dye or not to dye: a randomized, clinical trial of a triple dye/alcohol regime
      versus dry cord care.
AB  - OBJECTIVE: The use of antibacterial agents to clean and dry the stump of the
      newborn's umbilical cord after birth has recently been abandoned by many neonatal
      units in favor of dry cord care. The objective of this study was to compare cord
      bacterial colonization and morbidity among newborns whose cords were treated with
      triple dye and alcohol versus dry cord care. METHODOLOGY: We randomly allocated
      766 newborns to either 2 applications of triple dye to the umbilical cord stump
      on the day of birth with alcohol swabbing twice daily until the cord fell off (n
      = 384) or dry care (n = 382). Dry care consisted of spot cleaning soiled skin in
      the periumbilical area with soap and water, wiping it with a dry cotton swab or
      cloth, and allowing the area to air dry. Umbilical stumps on all subjects were
      swabbed and cultured. Community health nurses visiting at 2 or 3 days after
      hospital discharge observed the stump for signs of infection. Follow-up phone
      calls were made to mothers within 3 weeks of discharge. RESULTS: One infant in
      the dry care group was diagnosed with omphalitis. The umbilical stump was
      colonized with alpha-hemolytic streptococcus and coagulase-negative
      staphylococcus. Infants in the dry care group were significantly more likely to
      be colonized with Escherichia coli (34.2% vs 22.1%), coagulase-negative
      staphylococci (69.5% vs 50.5%), Staphylococcus aureus (31.3% vs 2.8%), and group
      B streptococci (11.7% vs 6.0%). Community health nurses were significantly more
      likely to observe exudate (7.4% vs 0.3%) and foul odor (2.9% vs 0.7%) among
      infants allocated to the dry care group during the home visit. CONCLUSIONS:
      Omphalitis remains a clinical issue. Cessation of bacteriocidal care of the
      umbilical stump must be accompanied by vigilant attention to the signs and
      symptoms of omphalitis.

PMID- 12509549
TI  - Effects of a videotape to increase use of poison control centers by low-income
      and Spanish-speaking families: a randomized, controlled trial.
AB  - BACKGROUND: Poison control centers (PCCs) reduce health care costs for childhood
      poisonings by providing telephone advice for home management of most cases. Past
      research suggests that PCCs are underutilized by low-income minority and Spanish
      speaking parents because of lack of knowledge and misconceptions about the PCC. A
      videotape intervention was designed to address these barriers to PCC use.
      OBJECTIVE: To evaluate the effectiveness of a videotape intervention (videotape,
      PCC pamphlet, and PCC stickers) in improving knowledge, attitudes, behaviors, and
      behavioral intention regarding use of the PCC in a low-income and predominantly
      Spanish-speaking population in Northern California. METHODS: Two hundred eighty
      nine parents of children <6 years of age, attending educational classes at 2
      Women, Infant, and Children (WIC) clinics participated in a randomized,
      controlled trial. WIC classes were randomized to receive the video intervention
      (video group) or to attend the regularly scheduled WIC class (control group).
      Participants completed a baseline questionnaire and 2 to 4 weeks later, a follow
      up telephone interview. Changes from baseline to posttest were compared in the
      treatment and control groups using analysis of variance. RESULTS: Compared with
      the control group, the video group showed an increase in knowledge about the
      PCC's function, its hours of operation, and staff qualifications; was more likely
      to feel confident in speaking with and carrying out recommendations made by the
      PCC; was less likely to believe the PCC would report a mother for neglect; was
      more likely to have the correct PCC phone number posted in their homes; and when
      presented with several hypothetical emergency scenarios, was more likely to
      correctly answer that calling the PCC was the best action to take in a poisoning
      situation. CONCLUSIONS: This videotape intervention was highly effective in
      changing knowledge, attitudes, behaviors, and behavioral intentions concerning
      the PCC within this population. As a result, use of this video may help increase
      use of the PCC by low-income and Spanish-speaking families.

PMID- 12509550
TI  - Lowered electroencephalographic spectral edge frequency predicts the presence of
      cerebral white matter injury in premature infants.
AB  - OBJECTIVE: Current methods for early identification of cerebral white matter
      injury in the premature infant at the bedside are inadequate. This study
      investigated the utility of advanced spectral analysis of the neonatal
      electroencephalogram (EEG) in the early diagnosis of white matter injury in the
      premature infant. The critical measurement used, suggested largely by previous
      studies in animal models, was the spectral edge frequency (SEF), calculated here
      as the frequency below which 90% of the power in the EEG exists. METHODS: Fifty
      nine very low birth weight infants (87% of eligible infants) had electrodes
      placed over the central and parietal regions (C3, P3, C4, and P4 sites according
      to the 10-20 international system) for the collection of EEG amplitude,
      intensity, and SEF. All averaged signals were analyzed off-line using software
      (Chart Analyzer; BrainZ Instruments, Auckland, NZ). All infants had a magnetic
      resonance imaging scan at term to identify the presence and severity of white
      matter injury. RESULTS: There was no significant difference between conventional
      EEG amplitude and intensity for infants with or without evidence of white matter
      injury. However, premature infants with increasingly severe white matter injury
      had progressively lower SEFs compared with infants who did not exhibit white
      matter injury. CONCLUSIONS: These data suggest that SEF-based measures are useful
      for defining the presence and severity of white matter injury at the bedside.

PMID- 12509551
TI  - Early age of first drunkenness as a factor in college students' unplanned and
      unprotected sex attributable to drinking.
AB  - OBJECTIVE: Early age of drinking onset has been associated with a greater
      likelihood among adults of experiencing alcohol dependence, frequent heavy
      drinking even among nondependent drinkers, and an increased risk of motor vehicle
      crashes, unintentional injuries, and physical fights after drinking. This study
      explores whether first getting drunk at a younger age is associated with a
      greater likelihood of college students reporting that they had unplanned or
      unprotected sexual intercourse because of their drinking. METHODOLOGY: In 1999 11
      739 full-time 4-year college students from 128 randomly selected US colleges and
      universities completed a self-administered survey that asked them about their
      drinking practices and whether their drinking had caused them, since the
      beginning of the school year, to: 1) engage in unplanned sexual intercourse or 2)
      not use protection when having sex. RESULTS: Among college students who drink,
      those first drunk before age 13 compared with those never drank until age 19 or
      older had a 2.0 times greater odds of having unplanned sex and a 2.2 times
      greater odds of having unprotected sex reportedly because of drinking, even after
      controlling for age, race/ethnicity, marital status, parental drinking history,
      age of first smoking, and marijuana use. After further controlling for history of
      alcohol dependence and frequency of heavy drinking those first drunk before age
      13 had a 1.5 times greater odds of unplanned sex and a 1.7 times greater odds of
      unprotected sex reportedly because of drinking. CONCLUSIONS: Clinical,
      educational, legal, and community interventions to delay age of first getting
      drunk need to be coupled with efforts to prevent unplanned and unprotected sexual
      intercourse among US college students.

PMID- 12509552
TI  - Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth
      graders.
AB  - OBJECTIVE: To survey caffeine use by seventh-, eighth-, and ninth-graders and
      relate its use to age, sex, sleep characteristics, and day of week METHODS:
      Students kept a daily, 2-week diary of their sleep times and use of caffeine
      containing drinks and foods. Data were analyzed by fitted multiple regression
      models RESULTS: A total of 191 students participated. Caffeine intake ranged
      between 0 and 800 mg/d. Mean use over 2 weeks ranged up to 379.4 mg/d and
      averaged 62.7 mg/d (corrected for underrepresentation in our sample of boys, who
      consumed more caffeine). Higher caffeine intake in general was associated with
      shorter nocturnal sleep duration, increased wake time after sleep onset, and
      increased daytime sleep. SLEEP PATTERNS: Mean bedtime was 10:57 PM, and mean wake
      time was at 7:14 AM. Older children delayed bedtime longer on weekends, and
      younger ones had longer nightly sleep durations. Sleep duration lengthened on
      weekends, reflecting the combined effects of the circadian timing system and a
      mechanism that regulates the duration of sleep. Caffeine (soda) consumption also
      increased on weekends, for reasons that may be primarily social CONCLUSIONS:
      Regardless of whether caffeine use disturbed sleep or was consumed to counteract
      the daytime effect of interrupted sleep, caffeinated beverages had detectable
      pharmacologic effects. Limitation of the availability of caffeine to teenagers
      should therefore be considered.

PMID- 12509553
TI  - Are pubertal changes in girls before age 8 benign?
AB  - OBJECTIVE: The Lawson Wilkins Pediatric Endocrine Society recently issued new
      recommendations for the age at which puberty should be considered precocious,
      lowering the prevailing standards from 8 years to 7 years for white girls and to
      6 years for black girls. The new recommendations were based on a single
      epidemiologic study that focused on the conditions of premature thelarche and
      premature adrenarche (both characterized by a single sign of puberty). Although
      the data were available, the authors did not comment on the low incidence of true
      precocious puberty (characterized by breast and pubic hair development) in their
      population. The hypothesis for the present study is that the new recommendations
      lead to underdiagnosis of endocrine pathology METHODS: Using 29 International
      Classification of Diseases, Ninth Revision codes for diagnoses known to be
      associated with precocious puberty, we identified 1570 patient visits to our
      outpatient pediatric endocrinology clinic of white girls aged 7 to 8 and black
      girls aged 6 to 8 during a 5-year period RESULTS: Of the 1570 patient visits, 223
      unique patients were identified as having been referred for the sole finding of
      precocious pubertal development. These 223 patients carried no other endocrine
      diagnoses. Eleven patients (4.9%) were found to have no true breast buds and no
      terminally differentiated pubic hair. A total of 105 (47.1%) of 223 patients were
      found to have 2 signs of puberty, consistent with true precocious puberty
      according to the conventional guidelines of precocity of 8 years in girls.
      Overall, 12.3% of patients also had diagnoses of other endocrine conditions that
      included congenital adrenal hyperplasia, McCune-Albright syndrome, growth hormone
      deficiency, hypothyroidism, hyperinsulinism, pituitary adenoma, and
      neurofibromatosis. A total of 35.2% of girls with true precocious puberty
      exhibited bone ages >3 standard deviations above the mean, indicating markedly
      diminished growth potential CONCLUSIONS: We conclude that signs of puberty in 6-
      to 8-year-old girls should not be considered normal or benign. Implementation of
      the new guidelines for the evaluation of puberty will result in failure to
      identify conditions that respond to early intervention.

PMID- 12509554
TI  - Secular changes in sleep position during infancy: 1995-1998.
AB  - OBJECTIVE: Prone sleeping among infants has been associated with an increased
      risk of sudden infant death syndrome. The objective of this study was to compare
      factors associated with sleep position in 1995-1996 and 1997-1998 and to assess
      secular trends in use of prone infant sleep position from 1995 through 1998 among
      families stratified by race and education. METHODS: A prospective cohort study
      was conducted in eastern Massachusetts and northwest Ohio of 12 029 mothers of
      infants who weighed > or =2500 g at birth. Descriptive statistics and
      multivariate odds ratios were used to relate maternal and infant characteristics
      to prone and supine sleeping. RESULTS: A total of 14 206 mothers (25% of those
      eligible) were enrolled. A total of 12 029 mothers (85% of enrolled) responded to
      the 1-month and 11 552 mothers (81% of enrolled) responded to the 3-month follow
      up questionnaire. A decline in use of the prone sleep position and increase in
      use of the supine position was observed during the 4 years of the study. Factors
      associated with prone and supine sleep position were similar in 1995-1996 and
      1997-1998. In 1997-1998, use of prone sleeping at 1 month of age reached the goal
      of < or =10% only among infants of white and Asian women, married women, women
      who were older than 25 years, women who were college graduates, and women with
      incomes >$55 000 per year. At 3 months of age, however, prone sleeping increased
      to 12% to 17% in these groups. These same groups were most likely to use the
      supine position; 38% to 45% were supine at 1 month, increasing to 56% to 64% by 3
      months of age. However, as of the end of 1998, approximately 27% of infants of
      non-college-educated black and Hispanic mothers were placed to sleep in the prone
      position and only 20% to 30% were being placed to sleep in the supine position at
      3 months of age. CONCLUSIONS: Recommendations to avoid prone sleep position and
      especially the recommendation that supine sleep position is preferred have not
      been effectively delivered to black and Hispanic families and to families of low
      income and less than a college education.

PMID- 12509555
TI  - Carotid artery intimal-medial thickness and left ventricular hypertrophy in
      children with elevated blood pressure.
AB  - OBJECTIVES: To determine the association between carotid artery intimal-medial
      thickness (cIMT) and left ventricular mass index (LVMI) in children with elevated
      blood pressure. METHODS: Study subjects (n = 32; mean age: 13.9 +/- 2.7 years)
      were untreated new referrals to a pediatric hypertension clinic with confirmed
      elevated blood pressure. LVM was calculated from 2-dimensionally guided m-mode
      echocardiographic measurements of the left ventricle. LVMI was calculated as LVM
      (g)/height (m)2.7, and left ventricular hypertrophy (LVH) was defined as LVMI
      >95th percentile. Carotid artery duplex ultrasound was performed by protocol by
      experienced vascular sonographers who were unaware of the echocardiography
      results. The thickest IMT complex of the far wall of the distal common carotid
      artery was measured in longitudinal B-mode section using a high-resolution linear
      array of 8 MHz. RESULTS: The prevalence of LVH and increased cIMT was 41% and
      28%, respectively. Subjects with increased cIMT had higher LVMI (46.8 g/m2.7 vs
      31.4 g/m2.7) than those with normal cIMT. The LVH prevalence was 89% (8 of 9)
      among subjects with increased cIMT as compared with 22% (5 of 23) in subjects
      with normal cIMT. cIMT was positively correlated with body mass index (r = 0.43),
      interventricular septal thickness (r = 0.58), posterior wall thickness (r =
      0.54), and LVMI (r = 0.54). cIMT and LVMI were positively associated after
      accounting for age, gender, and body mass index. CONCLUSIONS: These findings
      raise the possibility that carotid duplex ultrasound, by indicating the presence
      of early arterial wall changes, may be useful for predicting other cardiovascular
      sequelae in hypertensive children.

PMID- 12509556
TI  - Overeating among adolescents: prevalence and associations with weight-related
      characteristics and psychological health.
AB  - OBJECTIVE: To assess the prevalence of overeating among adolescents and to
      examine associations between overeating and sociodemographic characteristics,
      weight status, dieting behaviors, body satisfaction, depressive mood, self
      esteem, and suicide. METHOD: A school-based sample of 4746 boys and girls in
      public middle and high schools in Minnesota completed the Project EAT (Eating
      Among Teens) survey and anthropometric measurements of height and weight.
      RESULTS: Overall, 17.3% of girls and 7.8% of boys reported objective overeating
      in the past year. Youths who engaged in overeating were more likely to be
      overweight or obese, to have dieted in the past year, to be trying to lose weight
      currently, and to report that weight and shape are very important to their
      overall feelings about self. Youths who met criteria for binge eating syndrome
      (high frequency of objective overeating with loss of control and distress
      regarding the binge eating) scored significantly lower on measures of body
      satisfaction and self-esteem and higher on a measure of depressive mood than
      those who reported either subclinical or no binge eating. Overeating was
      associated with suicide risk; more than one fourth of girls (28.6%) and boys
      (27.8%) who met criteria for binge eating syndrome reported that they had
      attempted suicide. CONCLUSIONS: Overeating among adolescents is associated with a
      number of adverse behaviors and negative psychological experiences. As the
      current study is cross-sectional, it is not possible to ascertain cause and
      effect. Future research should seek to identify whether objective overeating is
      an early warning sign of additional psychological distress or is a potential
      consequence of compromised psychological health. Clinical implications are
      discussed.

PMID- 12509557
TI  - Community norms on toy guns.
AB  - OBJECTIVE: Toy gun play has been associated with aggressive behavior, and it has
      been suggested that child health professionals counsel families on limiting
      exposure. Effective violence prevention counseling requires an understanding of
      norms regarding parental attitudes, practices, and influencing factors. Both
      theories of reasoned action and planned behavior emphasize that subjective norms
      and attitudes affect people's perceptions and intended behavior. Few normative
      data exist on this issue from a cross-section of families. By establishing
      behavioral norms and understanding the spectrum of parental attitudes, community
      sensitive and community-specific interventions for violence prevention can be
      developed. The objective of this study was to assess community norms on the topic
      of toy gun play from the perspective of parents. METHODS: An anonymous self
      report assisted survey was administered to a convenience sample of
      parents/guardians who visited child health providers at 3 sites: an urban
      children's hospital clinic, an urban managed care clinic, and a suburban private
      practice. The parent questionnaire included questions on child rearing attitudes,
      practice, and sociodemographic information. RESULTS: A total of 1004 eligible
      participants were recruited for the study; 922 surveys were completed
      (participation rate 92%). The 830 (90%) respondents who were parents and had
      complete child data were the focus of additional analysis. Regarding toy guns,
      67% of parents believed that it was never "OK for a child to play with toy guns,"
      and 66% stated that they never let their children play with toy guns. Parents who
      thought that it was okay for children to play with toy guns and allowed them to
      play with toy guns were more likely to be male parents, have male children, and
      be white. CONCLUSIONS: There is variability in norms regarding toy gun play among
      parents, with most discouraging toy gun play. Norms varied based on gender of the
      child, gender of the parent, and race. Understanding norms is a first step in
      designing effective community-sensitive interventions.

PMID- 12509558
TI  - Breast deformity in adolescence as a result of pneumothorax drainage during
      neonatal intensive care.
AB  - OBJECTIVE: During intensive care of newborns, a number of invasive techniques may
      be necessary for resuscitation. The margin of safety between effective treatment
      and iatrogenic damage is narrow. The objective of this study was to identify and
      discuss iatrogenic damage in females resulting from treatment of pneumothorax and
      to give neonatologists anatomically based advice for prevention. PATIENTS AND
      METHODS: We report 2 female patients (aged 13 and 16 years) born prematurely in
      whom breast deformity occurred caused by drainage of multiple pneumothoraces
      during intensive care. In an additional anatomic study, both hemithoraces of 5
      newborn female cadavers (n = 10) were dissected to measure the extension of the
      breast tissue. RESULTS: The anatomic investigations in newborns demonstrate that
      breast tissue extends vertically from the second or third rib to the sixth rib
      and from close to the sternal edge medially, almost to the anterior axillary line
      laterally. CONCLUSION: Psychological distress and corrective surgery because of
      deformed breasts in adolescent girls who have undergone drainage of
      pneumothoraces as newborns can be avoided by placing the skin incision in the
      anterior axillary line, maintaining a distance of 4 to 5 cm inferior to the
      nipple, and by inserting the chest drain through the fifth or sixth intercostal
      space during neonatal treatment.

PMID- 12509559
TI  - Response to intravenous immunoglobulin predicts splenectomy response in children
      with immune thrombocytopenic purpura.
AB  - OBJECTIVE: Response to intravenous immunoglobulin (IVIG) has been shown to
      predict response to splenectomy in adults with immune thrombocytopenic purpura
      (ITP). However, reports in children have been inconsistent. We sought to
      determine whether response to IVIG is predictive of response to splenectomy in
      children. METHODS: Thirty-two assessable children were identified by a
      retrospective chart review. Response was graded according to previously published
      criteria as follows: "excellent" (platelets >150 000 within 1 week), "good"
      (platelets between 50 000 and 150 000), and "poor" (platelets <50 000).
      "Response" refers to both splenectomy and IVIG, and response to splenectomy was
      counted only when it was durable. RESULTS: Twenty-one of 23 patients who had a
      good or excellent response to IVIG also had an excellent response to splenectomy.
      Six of 9 patients who had a poor response to IVIG also had a poor response to
      splenectomy. Response to IVIG was a sensitive predictor of response to
      splenectomy in 88% of patients. Response to IVIG had a specificity of 75%, a
      positive predictive value of 91%, and a negative predictive value of 67%.
      Response to prednisone and length of time to splenectomy were not correlated with
      splenectomy response. CONCLUSIONS: These results suggest that response to IVIG is
      predictive of response to splenectomy in children with chronic ITP. This
      correlation may be of value in deciding whether a splenectomy should be performed
      in children with chronic ITP.

PMID- 12509560
TI  - Iron overload in children who are treated for acute lymphoblastic leukemia
      estimated by liver siderosis and serum iron parameters.
AB  - OBJECTIVE: To evaluate a secondary liver iron overload and its fate in children
      who are treated conventionally for acute lymphoblastic leukemia and to assess
      whether serum soluble transferrin receptor (sTfR) is useful in detecting iron
      load. METHODS: Liver siderosis was estimated histologically from liver biopsy
      specimens of 30 children (aged 2.6-17.6 years) close to or at the end of therapy
      using total iron score (TIS). Serum iron parameters and sTfR were measured at the
      same time and in 22 patients 1 to 3 years after therapy. RESULTS: In 19 (63%) of
      30 patients, liver TIS was >15, indicating at least moderate iron overload. Serum
      ferritin, iron, and transferrin iron saturation levels were highest and
      transferrin level lowest in the patients with the highest liver iron content.
      Serum sTfR levels did not differ significantly between the patients with varying
      amounts of liver iron. TIS correlated most significantly positively with serum
      ferritin (r(S) = 0.899), transferrin iron saturation (r(S) = 0.764), and the
      amount of transfused red blood cells (r(S) = 0.783). Serum iron parameters
      normalized in most patients during the follow-up. In 3 (14%) of 22 patients,
      serum ferritin level remained high (>1000 microg/L). CONCLUSIONS: Long-term iron
      overload is detected in at least 14% of children after therapy for acute
      lymphoblastic leukemia. Serum sTfR is an inappropriate marker for liver iron
      overload, whereas ferritin seems to be the most useful serologic marker for it.

PMID- 12509561
TI  - Does the treatment of attention-deficit/hyperactivity disorder with stimulants
      contribute to drug use/abuse? A 13-year prospective study.
AB  - OBJECTIVE: To examine the impact of stimulant treatment during childhood and high
      school on risk for substance use, dependence, and abuse by young adulthood.
      METHODS: A total of 147 clinic-referred hyperactive children were followed
      approximately 13 years into adulthood (mean: 21 years old; range: 19-25). At
      adolescent (age 15) and adult follow-up, probands were interviewed about their
      use of various substances and duration of stimulant treatment. RESULTS: Duration
      of stimulant treatment was not significantly associated with frequency of any
      form of drug use by young adulthood. Stimulant-treated children had no greater
      risk of ever trying drugs by adolescence or any significantly greater frequency
      of drug use by young adulthood. Stimulant treatment in high school also did not
      influence drug use in adulthood except for greater use of cocaine. This
      difference was no longer significant after controlling for severity of attention
      deficit/hyperactivity disorder and conduct disorder in childhood, adolescence,
      and adulthood. Stimulant treatment in either childhood or high school was not
      associated with any greater risk for any formal Diagnostic and Statistical Manual
      of Mental Disorders, Third Edition, Revised drug dependence or abuse disorders by
      adulthood. Treatment with stimulants did not increase the risk of ever having
      tried most illegal substances by adulthood except for cocaine. Subsequent
      analyses showed that this elevated risk was primarily mediated by severity of
      conduct disorder by young adulthood and not by stimulant treatment in childhood.
      CONCLUSION: This study concurs with 11 previous studies in finding no compelling
      evidence that stimulant treatment of children with attention
      deficit/hyperactivity disorder leads to an increased risk for substance
      experimentation, use, dependence, or abuse by adulthood.

PMID- 12509562
TI  - Age at menarche and racial comparisons in US girls.
AB  - BACKGROUND: Concern regarding change in the onset of sexual maturation of US
      girls has increased the need for current information on age at menarche from a
      national sample. Previous reports have been sparse and interpretation has been
      limited because of the racial composition and ages of the samples. OBJECTIVE: The
      objectives of this study were to estimate the distribution of age at menarche for
      all US girls and for non-Hispanic white, black, and Mexican American girls in the
      Third National Health and Nutrition Examination Survey and to test for racial
      differences. DESIGN: Menstrual status data were collected from 2510 girls aged
      8.0 to 20.0 years. The Third National Health and Nutrition Examination Survey
      followed a complex, stratified, multistage probability cluster design. SUDAAN was
      used to calculate proportions of girls reaching menarche at an age. Ages at
      menarche were estimated by probit analysis at the ages at which 10%, 25%, 50%,
      75%, and 90% of the girls attained menarche. RESULTS: Less than 10% of US girls
      start to menstruate before 11 years, and 90% of all US girls are menstruating by
      13.75 years of age, with a median age of 12.43 years. This age at menarche is not
      significantly different (0.34 years earlier) than that reported for US girls in
      1973. Age at menarche for non-Hispanic black girls was significantly earlier than
      that of white girls at 10%, 25%, and 50% of those who had attained menarche,
      whereas Mexican American girls were only significantly earlier than the white
      girls at 25%. CONCLUSION: Overall, US girls are not gaining reproductive
      potential earlier than in the past. The age at menarche of non-Hispanic black
      girls is significantly earlier than that of non-Hispanic white and Mexican
      American girls.

PMID- 12509563
TI  - Screening and counseling for adolescent alcohol use among primary care physicians
      in the United States.
AB  - OBJECTIVE: To examine the prevalence and quality of alcohol prevention services
      delivered to adolescents in the United States. METHODS: A national, stratified
      random sample of pediatricians and family practitioners was drawn from the
      American Medical Association Masterfile. The response rate was 63%, and the final
      sample size was 1842 physicians. Quality of services delivered was assessed by 2
      scales: quality of screening (percentage of patients screened and depth of
      screening questions used) and quality of education (level of effectiveness of
      educational methods used and frequency of use). RESULTS: Although most physicians
      reported providing some degree of alcohol prevention services, their efforts were
      typically inconsistent, not in enough depth, and they failed to incorporate the
      most effective educational methods. Reported rates of universal screening and
      counseling were low, and younger adolescents were less likely to receive
      services. Physicians' beliefs about their alcohol management skills and
      perceptions of resource availability were the most consistent correlates of
      higher quality service. CONCLUSIONS: Prospective studies that elucidate the
      conditions under which individual physicians do and do not screen, as well as
      future efforts to educate physicians about the most effective brief intervention
      approaches, seem warranted.

PMID- 12509564
TI  - Effects of sufentanil on electroencephalogram in very and extremely preterm
      neonates.
AB  - OBJECTIVE: The electroencephalogram (EEG) is used in neonatal intensive care
      units to assess brain maturation and neurologic prognosis in preterm newborns.
      Most of these newborns are sedated by opioids because of long-term assisted
      ventilation. The aim of this study was to describe the effects of sufentanil on
      the EEG in preterm newborns and to evaluate the consequences of such a treatment
      on neurologic assessment. METHODS: Fifteen preterm newborns <28 days of
      extrauterine life were studied. All of them were sedated by sufentanil (initial
      bolus injection of 0.5 micro g/kg, followed by continuous infusion of 0.2 micro
      g/kg/h). Three EEGs were performed: the first before and during the bolus
      injection, the second in the 48 hours after the start of the continuous infusion,
      and the third at least 24 hours after the treatment was stopped. Qualitative and
      quantitative methods were used to analyze each EEG. RESULTS: EEG patterns were
      not affected by sufentanil treatment. Bolus injection and continuous infusion
      induced a significant increase of EEG discontinuity in preterm newborns affecting
      mean burst percentage and mean and maximum interburst duration. CONCLUSIONS: The
      present data demonstrate that EEG is affected by bolus injection and continuous
      infusion of sufentanil. Sedation must therefore be considered to avoid
      misinterpretation of EEGs.

PMID- 12509565
TI  - Major surgery within the first 3 months of life and subsequent biobehavioral pain
      responses to immunization at later age: a case comparison study.
AB  - OBJECTIVES: Pain exposure during early infancy affects the pain perception beyond
      infancy into childhood. The objective of this study was to examine whether major
      surgery within the first 3 months of life in combination with preemptive
      analgesia alters pain responses to immunization at 14 or 45 months and to assess
      whether these alterations are greater in toddlers with a larger number of
      negative hospital experiences. METHODS: Two groups of 50 toddlers each were
      compared: index group and control group. All index toddlers had participated
      within the first 3 months of their life in a randomized, clinical trial that
      evaluated the efficacy of preemptive morphine administration for postoperative
      analgesia. The controls were matched by type of immunization and community health
      care pediatrician. Pain reactions were recorded at routine immunization at either
      14 (measles-mumps-rubella immunization) or 45 months (diphtheria-tetanus
      trivalent polio immunization) of age. Outcome measures were facial reaction,
      coded by the Maximum Discriminative Facial Movement Coding System; heart rate
      (HR); and cortisol saliva concentration. Negative hospital experiences included
      number of operations requiring postoperative morphine administration, cumulative
      Therapeutic Intervention Scoring System scores, and length of stay in the
      intensive care unit or total hospitalization days. RESULTS: No differences were
      found between the index and control groups in the facial display of pain, anger,
      or sadness or in physiologic parameters such as HR and cortisol concentrations.
      Intragroup analyses of the index group showed that after measles-mumps-rubella
      vaccination, the number of negative hospital experiences correlated positively
      with the facial responsiveness and negatively with HR responses. No effect was
      seen after diphtheria-tetanus-trivalent polio immunization. CONCLUSIONS: Major
      surgery in combination with preemptive analgesia within the first months of life
      does not alter pain response to subsequent pain exposure in childhood. Greater
      exposure to early hospitalization influences the pain responses after prolonged
      time. These responses, however, diminish after a prolonged period of nonexposure.

PMID- 12509566
TI  - Urethrovaginal reflux--a common cause of daytime incontinence in girls.
AB  - OBJECTIVE: The objective of this study was to estimate the frequency of
      urethrovaginal reflux as the cause of daytime incontinence in school-age girls,
      and to study the characteristic symptoms and the effect of simple instructions
      intended to amend the problem. MATERIAL AND METHODS: Girls with urethrovaginal
      reflux were identified in a group of 169 girls, aged 7 to 15 years, referred to a
      specialist clinic because of daytime incontinence. They were evaluated by a
      noninvasive screening protocol, including a careful history and neurourologic
      examination, bladder diaries, urine analysis, uroflows, and residual urine
      determined by ultrasound. Girls with urethrovaginal reflux were instructed by a
      urotherapist on how to achieve better toilet habits. RESULTS: Urethrovaginal
      reflux was found in 21 (12.4%) of 169 girls as the sole (19) or contributing (2)
      cause of their daytime urinary incontinence. They all had a typical history of
      small leakage 5 to 10 minutes after voidings during the day, confirmed by a
      specific bladder diary. All were neurologically healthy, and all but 2 had a
      normal bladder function. The latter 2 girls had residual urine and asymptomatic
      bacteriuria. At follow-up after median 2 years, all girls were free from
      postmicturition leakage, but the 2 with residual urine remained daytime
      incontinent with cystometrically proven phasic detrusor overactivity.
      CONCLUSIONS: Urethrovaginal reflux is a common cause of urinary incontinence in
      girls. The diagnosis is easily obtained by an adequate history, completed with a
      specific bladder diary. The problem is easily resolved by proper voiding
      instructions.

PMID- 12509567
TI  - A smoking cessation intervention for parents of children who are hospitalized for
      respiratory illness: the stop tobacco outreach program.
AB  - OBJECTIVE: Parental smoking is associated with increased rates and severity of
      childhood respiratory illness. No previous studies have examined child
      hospitalization as an opportunity for parental smoking cessation. We evaluated
      the feasibility of implementing a smoking cessation intervention for parents at
      the time of child hospitalization for respiratory illness. METHODS: We performed
      a prospective cohort study of smoking parents who had a child who was admitted to
      an academic children's hospital for a respiratory illness between January and
      April 2000. All enrollees were offered the Stop Tobacco Outreach Program, which
      includes an initial motivational interview, written materials, nicotine
      replacement therapy (NRT), telephone counseling, and fax referral to parents'
      primary clinician. The primary outcome was completion of all 3 counseling
      sessions. Two-month follow-up outcomes were quit attempts, cessation, NRT use,
      primary care visits, household smoking prohibition, and satisfaction. RESULTS: A
      total of 126 smoking parents met eligibility criteria, and 71 (56%) enrolled in
      the study. Of the 71, 80% completed all counseling sessions and 56% accepted free
      NRT at the time of enrollment. At the 2-month follow-up, of the 71 initial
      enrollees, 49% reported having made a quit attempt that lasted at least 24 hours,
      21% reported not smoking a cigarette in the last 7 days, 27% reported having used
      NRT, and 38% had had a visit with their own primary clinician. The proportion of
      parents who reported rules prohibiting smoking in the house increased (29% vs
      71%). Parental rating of the overall usefulness of the program was 4.3 +/- 0.9 (1
      standard deviation) on the 5-point scale 1 = not at all and 5 = a great extent.
      CONCLUSIONS: This study demonstrates the feasibility of engaging parents in
      smoking cessation interventions at the time of child hospitalization for
      respiratory illness. Previous work done in a similar sample of parental smokers
      has shown extremely low ever-use rates of cessation programs. High rates of
      acceptance of in-hospital and telephone counseling in this study support the
      notion of child hospitalization as a teachable moment to address parental
      smoking.

PMID- 12509568
TI  - Cost-effectiveness analysis of predischarge monitoring for apnea of prematurity.
AB  - OBJECTIVE: It is standard practice to defer discharge of premature infants until
      they have achieved a set number of days without experiencing apnea. The duration
      of this period, however, is highly variable across institutions, and there is
      scant literature on its effectiveness or value-for-money. Our objective was to
      establish the economic impact of varying durations of predischarge observation
      for apnea of prematurity. METHODS: Using computer simulation, we compared the
      alternatives of hospital monitoring for 1 to 10 days, after apparent cessation of
      apnea, with no monitoring and with the next longest period of monitoring. The
      daily probability of apnea requiring stimulation after a given number of apnea
      free days was obtained from chart review of 216 infants, beginning on the day
      they attained both full feeds and temperature stability in an open crib. Baseline
      rates of survival or impairment, utilities for calculation of quality-adjusted
      life years (QALYs), outcomes for respiratory arrest at home, and long-run costs
      for neurodevelopmental impairment were derived from the literature. Hospital
      expenditures were obtained from itemized billing records for infants on each of
      the final 10 days of hospitalization and converted to costs using Medicare cost
      to-charge ratios. Costs are reported in 2000 US dollars. RESULTS: For infants
      born at 24 to 26 weeks' gestation, each additional day of monitoring cost from
      $41000 per QALY saved for the first day to >$130000 per additional QALY gained
      for the tenth day. Cost-effectiveness was poorer for infants who were born at
      gestational ages >30 weeks. Results were sensitive to the proportion of charted
      apneas requiring stimulation that would actually progress, without intervention,
      to respiratory arrest. CONCLUSIONS: In this model, the cost-effectiveness of
      predischarge monitoring for apnea of prematurity declined significantly as the
      duration of monitoring was increased. Consideration should be given to
      alternative uses for resources in formulating neonatal discharge guidelines.

PMID- 12509569
TI  - Prevalence of hepatitis C virus infection and risk factors in an incarcerated
      juvenile population: a pilot study.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection is the leading cause of liver
      failure in adulthood. Although the prevalence of HCV is reportedly as high as 80%
      in incarcerated adult populations, little is known about the prevalence of HCV in
      incarcerated juvenile populations. The purpose of this study was to determine the
      prevalence of HCV and high-risk behaviors in a population of incarcerated youths.
      METHODS: We conducted a cross-sectional prevalence study of HCV infection in
      youths who were admitted to a juvenile detention center between September 1999
      and January 2001. Subjects were asked questions regarding behaviors that might
      put them at risk for acquiring HCV, and blood was drawn for HCV antibody testing.
      Qualitative HCV RNA testing was performed on antibody-positive subjects. RESULTS:
      Seventy-four percent (n = 305) of youths consented to participate in the
      seroprevalence study. HCV risk behaviors were common in this population: sexual
      activity (70%), intravenous drug use (6%), intranasal drug use (32%), body
      piercing (53%), and tattoos (33%). Six study youths (2%) were HCV antibody
      positive; 4 of these subjects were also HCV RNA positive. HCV-positive status was
      significantly associated with history of intravenous drug use and having had a
      sexually transmitted disease. Only 17% of study participants could correctly
      identify behaviors that might put them at risk for HCV. CONCLUSIONS: The
      prevalence of HCV in incarcerated youths is higher than in the general pediatric
      population but not yet at adult levels of prevalence. Given the high prevalence
      of risk factors in this population, future studies should address the need for
      targeted HCV screening and education of incarcerated youths regarding risks for
      HCV.

PMID- 12509570
TI  - Rumination syndrome in children and adolescents: diagnosis, treatment, and
      prognosis.
AB  - OBJECTIVES: To characterize the clinical features, results of diagnostic testing,
      and treatment outcomes for children and adolescents with rumination syndrome.
      METHODS: Review of the medical records for all 147 patients ages 5 to 20
      diagnosed with rumination syndrome at our institution between 1975 and 2000. Data
      are presented as mean +/- the standard error of the mean. RESULTS: Sixty-eight
      percent were female. Age at diagnosis was 15.0 +/- 0.3 years. Symptom duration
      before diagnosis was 2.2 +/- 0.3 years, 73% missed school/work, and 46% had been
      hospitalized because of symptoms. Before diagnosis, 16 (11%) underwent surgery
      for evaluation or management of symptoms. Twenty-four (16%) had psychiatric
      disorders; 3.4% had anorexia or bulimia nervosa. All patients described
      postprandial regurgitation after almost every meal (2.7 +/- 0.1 meals per day).
      Weight loss was described by 42.2% (median: 7 kg). Additional symptoms included:
      abdominal pain, 38%; constipation, 21%; nausea, 17%; and diarrhea, 8%. Structural
      studies were normal. Gastric emptying of solids at 4 hours was delayed in 26 of
      56 patients. Esophageal pH testing in 24 patients showed reflux/regurgitation in
      54%. Gastroduodenal manometry in 65 patients showed characteristic rumination
      waves in 40%. Outcome data (at median follow-up 10 months) were available for 54
      patients. Symptoms resolved in 16 (30%) and improved in 30 (56%). CONCLUSIONS:
      Recognition of the clinical features of rumination syndrome in children and
      adolescents is essential; the diagnosis is often delayed and associated with
      morbidity. Extensive diagnostic testing is unnecessary. Early behavioral therapy
      is advocated, and patient outcomes are generally favorable.

PMID- 12509571
TI  - Acute backpack injuries in children.
AB  - OBJECTIVE: To identify the most common mechanisms and sites of injury associated
      with book backpacks in school-aged children, who present to the emergency
      department. This should help with the development of backpack injury prevention
      strategies. DESIGN: A descriptive analysis of The National Electronic Injury
      Surveillance System (NEISS) of the US Consumer Product Safety Commission (CPSC)
      National Injury Information Clearinghouse data on backpacks. SETTING: One hundred
      emergency department departments throughout the United States that participate in
      NEISS data collection served as the setting. PARTICIPANTS: All children between 6
      and 18 years old who were recorded in the NEISS database with a backpack-related
      injury were studied. METHODS: Patients were identified by review of the NEISS
      data from 1999-2000. We separated patient data by age, sex, location of injury,
      and mechanism of injury. RESULTS: There were 247 children with backpack injuries.
      The mean age was 11.8 years, and 50% were male. The most common injury location
      was the head/face (22%) followed by the hand (14%), wrist/elbow (13%), shoulder
      (12%), and foot/ankle (12%). The back ranked sixth (11%). Of these back injuries,
      59% were associated with carrying a backpack. The most common mechanism for
      injury was tripping over the backpack (28%), followed by wearing (13%), and
      getting hit by the backpack (13%). CONCLUSIONS: Although the CPSC data on
      backpack injuries is frequently quoted in articles relating backpacks with back
      injury, 89% of backpack injuries in our study do not involve the back. Our study
      does not support the hypothesis that back injury is the major problem with book
      backpacks in the emergency department setting.

PMID- 12509572
TI  - Bleeding tendency in children with Alagille syndrome.
AB  - OBJECTIVE: Spontaneous intracranial bleeding is now a widely recognized
      complication and cause of mortality in patients with Alagille syndrome. The
      pathogenesis of intracranial bleeding in these patients remains unclear. The aim
      of the study was to look for other sites of bleeding in these patients that could
      suggest a factor of multiorgan morbidity. METHODS: The records of 174 patients
      with Alagille syndrome were reviewed, and 38 (22%) patients without liver failure
      who experienced hemorrhage that led to a drop in hemoglobin level of at least 3
      g/dL or to blood transfusion were identified. RESULTS: In 38 patients, 49
      bleeding episodes occurred at a median age of 3.75 years (range: 1 month-27
      years). Seventeen patients had 23 episodes of spontaneous bleeding; 21 patients
      bled during surgery or other medical procedures, and 5 among these 21 patients
      also had a spontaneous bleeding episode. Nine patients bled at least twice.
      Median platelets count and prothrombin time were normal. Severe cholestasis
      existed in 33 patients. One patient has a deletion of the 20p12 region, and 13 of
      17 patients studied have a JAGGED1 mutation. Blood transfusion was necessary in
      23 patients. Eight patients died secondary to bleeding (4 after surgery, 2 after
      gastrointestinal bleeding, 1 after needle liver biopsy, and 1 after intracranial
      bleeding). CONCLUSION: These results suggest that patients with Alagille syndrome
      are at special risk for bleeding; this should be taken into account before
      deciding on an invasive procedure. The mechanism of the bleeding is still
      unclear; the role of hypercholesterolemia cannot be excluded, but it may be
      speculated that JAGGED1 signaling abnormalities may impair the hemostatic
      function.

PMID- 12509573
TI  - Outcomes research in pediatric settings: recent trends and future directions.
AB  - OBJECTIVE: Pediatric outcomes research examines the effects of health care
      delivered in everyday medical settings on the health of children and adolescents.
      It is an area of inquiry in its nascent stages of development. METHODS: We
      conducted a systematic literature review that covered articles published during
      the 6-year interval 1994-1999 and in 39 peer-reviewed journals chosen for their
      likelihood of containing child health services research. This article summarizes
      the article abstraction, reviews the literature, describes recent trends, and
      makes recommendations for future work. RESULTS: In the sample of journals that we
      examined, the number of pediatric outcomes research articles doubled between 1994
      and 1999. Hospitals and primary care practices were the most common service
      sectors, accounting for more than half of the articles. Common clinical
      categories included neonatal conditions, asthma, psychosocial problems, and
      injuries. Approximately 1 in 5 studies included multistate or national samples; 1
      in 10 used a randomized controlled trial study design. Remarkably few studies
      examined the health effects of preventive, diagnostic, long-term management, or
      curative services delivered to children and adolescents. CONCLUSIONS: Outcomes
      research in pediatric settings is a rapidly growing area of inquiry that is
      acquiring breadth but has achieved little depth in any single content area. Much
      work needs to be done to inform decision making regarding the optimal ways to
      finance, organize, and deliver child health care services. To improve the
      evidence base of pediatric health care, more effectiveness research is needed to
      evaluate the overall and relative effects of services delivered to children and
      adolescents in everyday settings.

PMID- 12509574
TI  - Does stimulant therapy of attention-deficit/hyperactivity disorder beget later
      substance abuse? A meta-analytic review of the literature.
AB  - OBJECTIVE: Concerns exist that stimulant therapy of youths with attention
      deficit/hyperactivity disorder (ADHD) may result in an increased risk for
      subsequent substance use disorders (SUD). We investigated all long-term studies
      in which pharmacologically treated and untreated youths with ADHD were examined
      for later SUD outcomes. METHODS: A search of all available prospective and
      retrospective studies of children, adolescents, and adults with ADHD that had
      information relating childhood exposure to stimulant therapy and later SUD
      outcome in adolescence or adulthood was conducted through PubMed supplemented
      with data from scientific presentations. Meta-analysis was used to evaluate the
      relationship between stimulant therapy and subsequent SUD in youths with ADHD in
      general while addressing specifically differential effects on alcohol use
      disorders or drug use disorders and the potential effects of covariates. RESULTS:
      Six studies--2 with follow-up in adolescence and 4 in young adulthood--were
      included and comprised 674 medicated subjects and 360 unmedicated subjects who
      were followed at least 4 years. The pooled estimate of the odds ratio indicated a
      1.9-fold reduction in risk for SUD in youths who were treated with stimulants
      compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95%
      confidence interval for odds ratio [OR]: 1.1-3.6). We found similar reductions in
      risk for later drug and alcohol use disorders (z = 1.1). Studies that reported
      follow-up into adolescence showed a greater protective effect on the development
      of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4).
      Additional analyses showed that the results could not be accounted for by any
      single study or by publication bias. CONCLUSION: Our results suggest that
      stimulant therapy in childhood is associated with a reduction in the risk for
      subsequent drug and alcohol use disorders.

PMID- 12509575
TI  - Less testing is needed in the emergency room after a first afebrile seizure.

PMID- 12509576
TI  - Child abuse by intentional iron poisoning presenting as shock and persistent
      acidosis.
AB  - A case of intentional iron poisoning presented to our hospital. The patient's
      persistent acidosis and the team's observation of maternal indifference indicated
      the diagnosis. This case should alert physicians to a potential source for
      intentional poisoning that is present in most homes with young infants.

PMID- 12509577
TI  - Cervical spine involvement in Larsen's syndrome: a case illustration.
AB  - We present the progressive clinical course of a child with myelopathy
      attributable to cervical spine abnormalities associated with Larsen's syndrome.
      After anterior and posterior cervical fusion, his preoperative symptoms of
      weakness, gait dysfunction, and hyperreflexia have improved at 9-month follow-up.
      The progressive course and importance of early referral and intervention should
      be of interest to the general pediatric community.

PMID- 12509578
TI  - Persistent and recurrent tinea corporis in children treated with combination
      antifungal/ corticosteroid agents.
AB  - BACKGROUND: Combination antifungal/corticosteroid preparations are widely used by
      nondermatologists in the treatment of superficial fungal infections in patients
      of all ages. Over half of the prescriptions written for the most commonly used
      combination agent clotrimazole 1%/betamethasone diproprionate 0.05% cream
      (Lotrisone, Schering, Kenilworth, NJ) were prescribed for children younger than 4
      years old. Our pediatric dermatology division has recently encountered a series
      of children with recurrent or persistent tinea corporis, especially tinea faciei,
      treated initially with combination antifungal/corticosteroid cream. METHODS: All
      children evaluated for tinea corporis in a university hospital pediatric
      dermatology clinic from January through June 2001 were identified from the clinic
      registry for a retrospective chart review. Response to therapy was confirmed by
      telephone survey and/or follow-up visits at least 1 month after clearing of
      infection. RESULTS: Six children ranging in age from 4 to 11 years were evaluated
      for tinea corporis in a pediatric dermatology clinic at our institution during
      the 6-month period. All 6 children were diagnosed clinically by their
      pediatrician with tinea corporis and initially treated with clotrimazole
      1%/betamethasone diproprionate 0.05% cream for 2 to 12 months. In our pediatric
      dermatology clinic, patients had their diagnosis confirmed with a positive
      potassium hydroxide preparation and were treated with one of several oral or
      topical antifungal agents with clearing of all tinea infections. CONCLUSION: The
      use of combination clotrimazole 1% cream/betamethasone diproprionate 0.05% cream
      (Lotrisone) for the treatment of tinea corporis may be associated with
      persistent/recurrent infection.

PMID- 12509579
TI  - Identifying and treating eating disorders.
AB  - Pediatricians are called on to become involved in the identification and
      management of eating disorders in several settings and at several critical points
      in the illness. In the primary care pediatrician's practice, early detection,
      initial evaluation, and ongoing management can play a significant role in
      preventing the illness from progressing to a more severe or chronic state. In the
      subspecialty setting, management of medical complications, provision of
      nutritional rehabilitation, and coordination with the psychosocial and
      psychiatric aspects of care are often handled by pediatricians, especially those
      who have experience or expertise in the care of adolescents with eating
      disorders. In hospital and day program settings, pediatricians are involved in
      program development, determining appropriate admission and discharge criteria,
      and provision and coordination of care. Lastly, primary care pediatricians need
      to be involved at local, state, and national levels in preventive efforts and in
      providing advocacy for patients and families. The roles of pediatricians in the
      management of eating disorders in the pediatric practice, subspecialty, hospital,
      day program, and community settings are reviewed in this statement.

PMID- 12509580
TI  - Recommended childhood and adolescent immunization schedule--United States, 2003.

PMID- 12509581
TI  - Acute otitis media: bunnies, disposables, and bacterial original sin!

PMID- 12509582
TI  - Why no effect of maternal respiratory syncytial virus-neutralizing antibody?

PMID- 12509583
TI  - Glucagon infusion for treatment of hypoglycemia: efficacy and safety in sick,
      preterm infants.

PMID- 12509584
TI  - Postnatal steroids to treat or prevent chronic lung disease in preterm infants.

PMID- 12509585
TI  - Social inequality in childhood diabetes--a population-based follow-up study in
      Germany.

PMID- 12509586
TI  - Prediction of adult overweight from childhood body mass index and not childhood
      height.

PMID- 12509587
TI  - Same-sex parenting.

PMID- 12509588
TI  - Systematic review of treatments for recurrent abdominal pain.
AB  - OBJECTIVE: To conduct a systematic review of evaluated treatments for recurrent
      abdominal pain (RAP) in children. METHODS: Online bibliographic databases were
      searched for the terms "recurrent abdominal pain," "functional abdominal pain,"
      "children," or "alternative therapies" in articles classified as randomized
      controlled trials. The abstracts or full text of 57 relevant articles were
      examined; 10 of these met inclusion criteria. Inclusion criteria required that
      the study involve children aged 5 to 18 years, subjects have a diagnosis of RAP,
      and that subjects were allocated randomly to treatment or control groups. The
      methodology and findings of these articles were evaluated critically, and data
      were extracted from each article regarding study methods, specific interventions,
      outcomes measured, and results. RESULTS: Studies that evaluated famotidine,
      pizotifen, cognitive-behavioral therapy, biofeedback, and peppermint oil enteric
      coated capsules showed a decrease in measured pain outcomes for those who
      received the interventions when compared with others in control groups. The
      studies that evaluated dietary interventions had conflicting results, in the case
      of fiber, or showed no efficacy, in the case of lactose avoidance. CONCLUSIONS:
      Evidence for efficacy of treatment of RAP in children was found for therapies
      that used famotidine, pizotifen, cognitive-behavioral therapy, biofeedback, and
      peppermint oil enteric-coated capsules. The effects of dietary fiber were less
      conclusive, and the use of a lactose-free diet showed no improvement. There
      seemed to be greater improvement when therapy (famotidine, pizotifen, peppermint
      oil) was targeted to the specific functional gastrointestinal disorder
      (dyspepsia, abdominal migraine, irritable bowel syndrome). The behavioral
      interventions seemed to have a general positive effect on children with
      nonspecific RAP. Many of these therapies have not been used widely as standard
      treatment for children with RAP. Although the mechanism of action for each
      effective therapy is not fully understood, each is believed to be safe for use in
      RAP.

PMID- 12509589
TI  - Suction-type suffocation incidents in infants and toddlers.
AB  - OBJECTIVES: To describe the danger of upper airway obstruction associated with
      semirigid hollow objects in infants and toddlers and to define a minimum
      frequency with which episodes involving these products have occurred and propose
      a model defining the potentially hazardous characteristics of these objects.
      METHODS: A retrospective study of incidents reported to the US Consumer Product
      Safety Commission from January 1983 to March 2000, involving children younger
      than 5 years, was conducted. The medical literature (Medline) was searched for
      similar cases. The resulting case series was analyzed. RESULTS: A total of 17
      incidents were identified in which a semirigid, hollow hemispherical/ellipsoidal
      object was described as having "cupped" the face, simultaneously covering the
      nose and the mouth. Of the 17 incidents, 13 involved toys; the remaining 4
      incidents involved 2 different consumer products. All of these incidents involved
      children aged 4 to 36 months. Eight incidents resulted in death; 9 were nonfatal
      because of parental intervention. In all cases investigated, the infant was found
      with the semirigid object strongly adhering to his or her face. In 16 incidents,
      significant physical effort reportedly was required to remove the objects from
      the child's face. The fatal incidents involved children aged 4 to 24 months,
      whereas the age range of the children in nonfatal incidents was 7 to 36 months.
      In all but 1 of the fatal cases, the victim was found dead in a crib or playpen.
      The cross-sectional diameter of the products involved in suffocation incidents
      was in the range of 6.4 to 9.7 cm. The depths of the products ranged from 4.2 to
      5.1 cm. The approximate volume of containers ranged between 100 and 170 mL. These
      dimensions are compatible with the range of anthropometric measurements that
      allow the product to fit snugly over the mouth and the nose of a young child,
      resulting in complete airway obstruction. CONCLUSIONS: Children between the ages
      of 4 and 36 months are at risk from suffocation by hollow, semirigid
      hemispherical/ellipsoidal objects through suction formation and complete airway
      obstruction. Shallow containers with dimensions ranging from approximately 6.0 to
      11.0 cm seem to be especially hazardous. Several recommendations may be proposed
      to lessen the hazard to young children. These include product design changes that
      limit the amount of contact with the perimeter and reduce the chance of forming a
      seal between the container and the face and ventilation holes to prevent a seal
      from forming. Although design change alone may be very helpful in products that
      are intended for use by children who are younger than 3 years, products that have
      similar dimensions and are not intended for infants present additional
      challenges. Thus, a very important additional prevention strategy is education.
      Pediatricians and other health care providers should alert parents and caregivers
      to the dangers of leaving such products in an infant's crib or playpen or
      allowing infants to play with these objects while unattended.

PMID- 12509590
TI  - Sleepwalking and sleep terrors in prepubertal children: what triggers them?
AB  - OBJECTIVES: To evaluate the clinical presentation and polysomnography of
      prepubertal children with repetitive sleep terrors and sleepwalking, to compare
      them with a control group, and to evaluate the treatment of associated sleep
      disorders. METHODS: Patients with complaint of sleep terrors with or without
      sleepwalking were studied retrospectively. A control group was also recruited.
      Each subject received a standardized evaluation, which included the following: 1)
      Pediatric Sleep Questionnaire; 2) interview regarding child's medical and
      sociofamilial history, orthodontic history, schooling, psychological
      difficulties, medication intake, and family history of medical and sleep
      disorders; 3) general pediatric physical examination and neurologic,
      otolaryngological, and craniofacial examination by a specialist; 4) obtaining
      medical history on variables relevant to early life sleep disorders; 5)
      polysomnography, which included electroencephalogram (EEG; C3/A2, Fp1/T1, T1/O1,
      O1/C3, C4/A1, Fp2/T2, T2/O2, O2/C4), chin and leg electromyelogram, right and
      left electro-oculogram, and electrocardiogram (modified V2 lead); respiration was
      monitored with a nasal cannula/pressure transducer system, mouth thermistor,
      chest and abdominal bands, pulse oximeter, and neck microphone; respiratory
      effort was monitored with calibrated esophageal manometry; variables were
      collected on a computerized sleep system; and 6) available family members with a
      positive history of sleep terrors and sleepwalking received clinical evaluations
      similar to those used for index cases; they also underwent ambulatory monitoring
      with an Edentrace system, which monitors heart rate, body position, oro-nasal
      flow, chest impedance, breathing noises (neck microphone), and pulse oximetry.
      Movements are deduced from artifact, and leg movements may be recorded on one
      channel if the equipment is preset for such recording. Subjects used logs to
      record "lights out" time, "lights on" time, nocturnal awakenings, and other
      events that occurred during the night. All original and follow-up recordings were
      rescored by 2 of 4 randomly selected specialists who were blind to subject
      identity. Mann-Whitney U test was used for group comparison. Nonparametric chi2
      test was used to compare percentages of symptoms in symptomatic children versus
      control children. RESULTS: Eighty-four children (5 with sleep terrors and 79 with
      both sleep terrors and sleepwalking) and 36 normal control children formed the
      studied population. All subjects were Tanner stage 1 (prepubertal). None of the
      control children had any parasomnias. Fifty-one (61%) of 84 children with
      parasomnia had a diagnosis of an additional sleep disorder: 49 with sleep
      disordered breathing (SDB) and 2 with restless leg syndrome (RLS). Twenty-nine of
      the children with both parasomnia and SDB had a positive family history of
      parasomnias, and 24 of the 29 also had a positive family history of SDB. Of the
      51 children with associated sleep disorders, 45 were treated. Forty-three of 49
      children with SDB were treated with tonsillectomy, adenoidectomy, and/or
      turbinate revision, and 2 of 2 children with RLS were treated with Pramipexole, a
      dopamine agonist, at bedtime. Treatment of the precipitating sleep disorder
      eliminated parasomnias in all 45 children. In all 43 children who received
      surgery, polysomnography performed 3 to 4 months later indicated the
      disappearance of SDB. The recordings also showed an absence of confusional
      arousals. The number of EEG arousals significantly decreased from a mean of 9 +/-
      2.6 EEG arousals > or =3 seconds/hour during total sleep time to 3 +/- 1.5. The
      number of EEG arousals > or =3 seconds during the first sleep cycle of slow wave
      sleep (stage 3-4 non-rapid eye movement sleep) decreased from 4 +/- 1.4 to 1 +/-
      0.2. In all surgically treated cases, parents also reported subsequent absence of
      the parasomnia. The 2 symptomatic children who were treated with Pramipexole had
      a complete absence of confusional arousals on the follow-up recording and
      reported no parasomnia since treatment. The periodic limb movemia since
      treatment. The periodic limb movement syndrome arousal index (number of EEG
      arousals associated with periodic limb movement/hour) decreased from 11 and 16 to
      0 and 0.2, respectively. Parasomnia persisted in the 6 children who were
      untreated for SDB. Surgeons had refused to perform surgery on these children
      because of lack of data on the relationship between parasomnia and SDB-related
      tonsil and adenoid enlargement. CONCLUSION: Children with chronic parasomnias may
      often also present SDB or, to a lesser extent, RLS. Furthermore, the
      disappearance of the parasomnias after the treatment of the SDB or RLS periodic
      limb movement syndrome suggests that the latter may trigger the former. The high
      frequency of SDB in family members of children with parasomnia provided
      additional evidence that SDB may manifest as parasomnias in children. Children
      with parasomnias are not systematically monitored during sleep, although past
      studies have suggested that patients with sleep terrors or sleepwalking have an
      elevated level of brief EEG arousals. When children receive polysomnographies,
      discrete patterns (eg, nasal flow limitation, abnormal respiratory effort, bursts
      of high theta or slow alpha EEG frequencies) should be sought; apneas are rarely
      found in children. Children's respiration during sleep should be monitored with
      nasal cannula/pressure transducer system and/or esophageal manometry, which are
      more sensitive than the thermistors or thermocouples currently used in many
      laboratories. The clear, prompt improvement of severe parasomnia in children who
      are treated for SDB, as defined here, provides important evidence that subtle SDB
      can have substantial health-related significance. Also noteworthy is the report
      of familial presence of parasomnia. Studies of twin cohorts and families with
      sleep terror and sleepwalking suggest genetic involvement of parasomnias. RLS and
      SDB have been shown to have familial recurrence. RLS has been shown to have
      genetic involvement. It remains to be investigated whether a genetic factor
      directly influences sleep terror and sleepwalking or instead influences other
      disorders that fragment sleep and lead to confusional arousals. Additional
      studies are needed to investigate the association between SDB and non-;rapid eye
      movement parasomnias in the general population.

PMID- 12509591
TI  - Evaluation of a peer-reviewed career development and compensation program for
      physicians at an academic health science center.
AB  - OBJECTIVE: The Department of Pediatrics at the Hospital for Sick Children, which
      is funded by an alternative payment plan, has implemented a novel career
      development and compensation program (CDCP). Job activity profiles were used to
      more clearly define job expectations, benchmarks guided career development, and
      peer review was used to assess performance. The objective of this study was to
      evaluate the departmental pediatricians' satisfaction with the CDCP. METHODS:
      Pediatricians, all of whom had undergone CDCP annual reviews, could participate
      if they had undergone the in-depth triennial CDCP review. Each received a 5-point
      Likert scale-based questionnaire that asked how well the CDCP had conformed to
      the principles identified by the department during the development of the CDCP.
      Anonymous, confidential responses were collated and used to guide focus groups
      that discussed areas of greatest concern and attempted to identify solutions.
      Focus groups were led by external facilitators who were experienced in
      qualitative research. They audiotaped the sessions, transcribed the comments, and
      analyzed the data with the assistance of a qualitative analysis application.
      RESULTS: Sixty of the eligible 88 pediatricians participated, and 74% of their
      responses were that the CDCP had addressed the original principles "somewhat,"
      "to a great extent," or "extremely well." The remainder indicated that some of
      the principles were either "not addressed" or "only to a small extent" by the
      CDCP. Results from the 11 focus groups (46 participants) indicated that the CDCP
      was an improvement over the previous method of career development and
      determination of the rate of remuneration. Most were also still in agreement with
      the purpose and design principles. Although they did not want the CDCP to undergo
      a major redesign, they identified areas that need improvement. Short-, medium-,
      and long-term action plans to address these areas are under way. CONCLUSION:
      Pediatricians at the health science center of the Hospital for Sick Children
      remain supportive of the CDCP.

PMID- 12509592
TI  - Sustaining and broadening intervention impact: a longitudinal randomized trial of
      3 adolescent risk reduction approaches.
AB  - OBJECTIVE: To determine whether the addition of a parental monitoring
      intervention (Informed Parents and Children Together [ImPACT]) alone or with
      "boosters" could enhance (either broaden or sustain or both) the effect of a
      small group, face-to-face adolescent risk reduction intervention Focus on Kids
      (FOK). METHODS: A longitudinal, randomized, community-based cohort study was
      conducted of 35 low-income, community-based, in-town settings. A total of 817
      black youths aged 12 to 16 years at baseline were studied. After completion of
      baseline measures, youths were randomized to receive a face-to-face intervention
      alone (FOK only), a face-to-face intervention and a parental monitoring
      intervention (FOK plus ImPACT), or both of the above plus boosters (FOK plus
      ImPACT plus boosters). Risk and protective behaviors were assessed at 6 and 12
      months after intervention. RESULTS: At 6 months' follow-up, youths in families
      that were assigned to FOK plus ImPACT reported significantly lower rates of
      sexual intercourse, sex without a condom, alcohol use, and cigarette use and
      marginally lower rates of "risky sexual behavior" compared with youths in
      families that were assigned to FOK only. At 12 months after intervention, rates
      of alcohol and marijuana use were significantly lower and cigarette use and
      overall risk intention were marginally lower among FOK plus ImPACT youths
      compared with FOK only youths. With regard to the boosters delivered at 7 and 10
      months, 2 risk behaviors--use of crack/cocaine and drug selling--were
      significantly lower among the youths who were assigned to receive the additional
      boosters compared with youths without the boosters. The rates of the other risk
      behaviors and intentions did not differ significantly. CONCLUSIONS: The results
      of this randomized, controlled trial indicate that the inclusion of a parental
      monitoring intervention affords additional protection from involvement in
      adolescent risk behaviors 6 and 12 months later compared with the provision of an
      intervention that targets adolescents only. At the same time, the results of the
      present study do not provide sufficient evidence that booster sessions further
      improve targeted behaviors enough to include them in a combined parent and youth
      intervention.

PMID- 12509593
TI  - Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy
      and lactation augments children's IQ at 4 years of age.
AB  - OBJECTIVES: Docosahexaenoic acid (DHA; 22:6 n-3) and arachidonic acid (AA; 20:4 n
      6) are important for development of the central nervous system in mammals. There
      is a growth spurt in the human brain during the last trimester of pregnancy and
      the first postnatal months, with a large increase in the cerebral content of AA
      and DHA. The fetus and the newborn infant depend on maternal supply of DHA and
      AA. Our hypothesis was that maternal intake of DHA during pregnancy and lactation
      is marginal and that high intake of this fatty acid would benefit the child. We
      examined the effect of supplementing pregnant and lactating women with very-long
      chain n-3 polyunsaturated fatty acids (PUFAs; cod liver oil) on mental
      development of the children, compared with maternal supplementation with long
      chain n-6 PUFAs (corn oil). METHODS: The study was randomized and double-blinded.
      Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver
      oil or corn oil until 3 months after delivery. The cod liver oil contained 1183
      mg/10 mL DHA, 803 mg/10 mL eicosapentaenoic acid (20:5 n-3), and a total of 2494
      mg/10 mL summation operator n-3 PUFAs. The corn oil contained 4747 mg/10 mL
      linoleic acid (18:2 n-6) and 92 mg/10 mL alpha-linolenic acid (18:3 n-3). The
      amount of fat-soluble vitamins was identical in the 2 oils (117 micro g/mL
      vitamin A, 1 micro g/mL vitamin D, and 1.4 mg/mL dl-alpha-tocopherol). A total of
      590 pregnant women were recruited to the study, and 341 mothers took part in the
      study until giving birth. All infants of these women were scheduled for
      assessment of cognitive function at 6 and 9 months of age, and 262 complied with
      the request. As part of the protocol, 135 subjects from this population were
      invited for intelligence testing with the Kaufman Assessment Battery for Children
      (K-ABC) at 4 years of age. Of the 135 invited children, 90 came for assessment.
      Six children did not complete the examination. The K-ABC is a measure of
      intelligence and achievement designed for children aged 2.5 years through 12.5
      years. This multisubtest battery comprises 4 scales: Sequential Processing,
      Simultaneous Processing, Achievement (not used in the present study), and
      Nonverbal Abilities. The Sequential Processing and Simultaneous Processing scales
      are hypothesized to reflect the child's style of problem solving and information
      processing. Scores from these 2 scales are combined to form a Mental Processing
      Composite, which serves as the measure of intelligence in the K-ABC. RESULTS: We
      received dietary information from 76 infants (41 in the cod liver oil group and
      35 in the corn oil group), documenting that all of them were breastfed at 3
      months of age. Children who were born to mothers who had taken cod liver oil (n =
      48) during pregnancy and lactation scored higher on the Mental Processing
      Composite of the K-ABC at 4 years of age as compared with children whose mothers
      had taken corn oil (n = 36; 106.4 [7.4] vs 102.3 [11.3]). The Mental Processing
      Composite score correlated significantly with head circumference at birth (r =
      0.23), but no relation was found with birth weight or gestational length. The
      children's mental processing scores at 4 years of age correlated significantly
      with maternal intake of DHA and eicosapentaenoic acid during pregnancy. In a
      multiple regression model, maternal intake of DHA during pregnancy was the only
      variable of statistical significance for the children's mental processing scores
      at 4 years of age. CONCLUSION: Maternal intake of very-long-chain n-3 PUFAs
      during pregnancy and lactation may be favorable for later mental development of
      children.

PMID- 12509594
TI  - Bronchiolitis management preferences and the influence of pulse oximetry and
      respiratory rate on the decision to admit.
AB  - OBJECTIVE: High incidence, rising admission rates, and relatively ineffective
      therapies make the management of bronchiolitis controversial. Since 1980, the
      rate of hospitalization for children with bronchiolitis has increased by nearly
      250%, whereas mortality rates for the disease have remained constant. It has been
      speculated that the increasing use of pulse oximetry has lowered the threshold
      for admission and may have contributed to the rise in bronchiolitis-related
      admissions. The objective of this study was to describe pediatric emergency
      medicine physicians' management preferences regarding infants with moderately
      severe bronchiolitis and to assess the influence of specific differences in
      oxygen saturation as measured by pulse oximetry (SpO2) and respiratory rate (RR)
      on the decision to admit. METHODS: Physicians who are members of the American
      Academy of Pediatrics Section of Emergency Medicine and living in the United
      States were randomized into 4 groups and mailed a survey that contained 1 of 4
      vignettes. Vignettes were identical except for given SpO2 values (94% or 92%) and
      RR (50/min or 65/min). Subjects were asked to answer questions regarding
      laboratory tests, treatment options, and the decision to admit for the patient in
      their vignette. RESULTS: We received completed surveys from 519 (64%) of the 812
      physicians contacted. Most respondents recommended use of bronchodilators (96%),
      nasal suction (82%), and supplemental oxygen (57%). Few respondents recommended
      decongestants (9%), steroids (8%), or antibiotics (2%). When asked to rank
      therapies, respondents gave nasal suction 182 number 1 votes; bronchodilators
      received 164. The decision to admit varied with SpO2 and RR. Forty-three percent
      of respondents who received a vignette featuring SpO2 of 94% and a RR of 50/min
      recommended admission for the infant in their vignette. Fifty-eight percent
      recommended admission when the vignette SpO2 was 94% and RR was 65/min (chi2 =
      5.021). Respondents who received a vignette with SpO2 of 92% were nearly twice as
      likely to recommend admission: 83% recommended admission when vignette RR was
      50/min, and 85% recommended admission when vignette RR was 65/min (chi2 = 0.126).
      CONCLUSIONS: When treating infants with moderately severe bronchiolitis,
      pediatricians who work in emergency departments frequently use bronchodilators
      and nasal suction, 2 practices for which supporting data are either conflicting
      (bronchodilators) or nonexistent (nasal suction). In addition, their decisions to
      admit differ markedly on the basis of only a 2% difference in SpO2. It is
      possible that increased reliance on pulse oximetry has contributed to the
      increase in bronchiolitis hospitalization rates seen during the past 2 decades.

PMID- 12509595
TI  - Height, weight, and growth in children born to mothers with HIV-1 infection in
      Europe.
AB  - OBJECTIVES: Little is known about the independent long-term effect on growth of
      exposure to maternal human immunodeficiency virus (HIV) infection. Growth
      patterns in uninfected children who are born to infected mothers have not been
      described in detail previously beyond early childhood, and patterns over age for
      infected and uninfected children have not been based on appropriate general
      population standards. In vertically HIV-infected children, poor growth has been
      suggested to be an early marker of infection or progression of disease. However,
      whether growth faltering is an independent HIV-related symptom or caused
      indirectly by other HIV clinical symptoms requires clarification. This
      information is needed to inform the debate on a possible effect of antiretroviral
      combination therapy on the height of infected children and would provide evidence
      for the use of specific interventions to improve height. The objective of this
      study was to describe growth (height and weight) patterns in infected and
      uninfected children who are born to HIV-infected mothers with respect to
      standards from a general population and to assess age-related differences in
      height and weight by infection status, allowing for birth weight, gestational
      age, gender, HIV-related clinical status, and antiretroviral therapy (ART).
      METHODS: Since 1987, children who were born to HIV-infected mothers in 11 centers
      in 8 European countries were enrolled at birth in the European Collaborative
      Study and followed prospectively according to a standard protocol. Height and
      weight were measured at every visit, scheduled at birth; 3 and 6 weeks; 3, 6, 9,
      12, 15, 18, and 24 months; and every 6 months thereafter. Serial measurements of
      height and weight from birth to 10 years of age of 1403 uninfected and 184
      infected children were assessed. We fitted linear mixed effects models allowing
      for variance changes over age and within-subject correlation using fractional
      polynomials and natural cubic splines. Growth patterns were compared with British
      1990 growth standards and by infection status. RESULTS: Of the 1587 children
      enrolled, 810 were male and 777 were female; 1403 were not infected (681 boys,
      722 girls), and 184 were infected (88 boys, 96 girls). Neither height nor weight
      was associated significantly with the main effects of HIV infection status at
      birth, but differences between infected and uninfected children increased with
      age. Uninfected children had normal growth patterns from early ages. Infected
      children were estimated to be significantly shorter and lighter than uninfected
      children with growth differences increasing with age. Differences in growth
      velocities between the infected and uninfected children increased after 2 years
      of age for height and after 4 years of age for weight and were more marked in the
      latter. Between 6 and 12 months, uninfected children grew an estimated 1.6%
      faster in height and 6.2% in weight than infected children; between ages 8 and 10
      years, these figures were 16% and 44%, respectively. By 10 years, uninfected
      children were on average an estimated 7 kg heavier and 7.5 cm taller than
      infected children. Growth in uninfected children who were born before 1994,
      before the widespread use of ART prophylaxis to reduce vertical transmission, did
      not substantially differ from that of children who were born after 1994. To
      investigate whether the growth differences between infected and uninfected
      children were associated with HIV disease progression, we analyzed growth of
      infected children using the Centers for Disease Control and Prevention (CDC)
      clinical classification, in 3 groups: no symptoms, mild or moderate symptoms (A
      and B), and severe symptoms (C or death). Infected children with mild or serious
      symptoms lagged behind asymptomatic children in both height and weight, and these
      differences increased with age. Infected children who were born before
      availability of ART, before 1988, were more likely to reach a weight below the
      third centile for age than children who were born after 1994 when effective HIV
      treatment was widely available. Of the 184 infected children, 67 had been weighed
      and/or measured at least once while on combination (> or = 2 drugs) ART.
      Reflecting the longitudinal nature of the European Collaborative Study and the
      changing availability of HIV treatment, most of these measurements took place
      after 7 years of age, and therefore analyzing the possible effect of combination
      therapy on growth is difficult. The z scores for height and weight gain improved
      substantially in several children who received combination therapy regardless of
      their CDC clinical classification. To increase available information, we pooled
      all measurements according to CDC clinical classification and presence of
      combination therapy at the time of the observation. Weight and height
      significantly improved for severely ill children after combination therapy.
      CONCLUSION: Using data from this large prospective European study, we
      investigated in comparison with general British standards growth patterns in the
      first 10 years of life of HIV-infected and uninfected children who were born to
      HIV-infected mothers. The duration of follow-up of uninfected as well as infected
      children makes this a unique data set. We allowed for repeated measurements for
      each child and the increase of variability in height and weight with age. Growth
      faltering may be related to the social environment, and our finding that
      uninfected children have normal growth, which is unaffected by exposure to
      maternal HIV infection, is consistent with observations that in Europe the HIV
      infected population is more like the general population and less
      socioeconomically disadvantaged than that in the United States. However, HIV
      infected children grew considerably slower, and differences between infected and
      uninfected children increased with age. Growth patterns in asymptomatic infected
      children were similar to those with only mild or moderate symptoms. However,
      compared with these 2 groups combined, severely ill children had poorer growth at
      all ages. Although limited by the small number of children who received
      combination therapy, severely ill children may benefit from such therapy in terms
      of improvements in weight and, to a smaller extent, in height. Growth faltering,
      particularly stunting, may adversely affect a child's quality of life, especially
      once they reach adolescence, and this should be taken into account when making
      decisions about starting and changing ART. Additional research will help to
      elucidate the relationship between combination therapy and improved growth, in
      particular regarding different regimens and the best timing of initiation for
      optimizing growth of infected children.

PMID- 12509596
TI  - US birth weight/gestational age-specific neonatal mortality: 1995-1997 rates for
      whites, hispanics, and blacks.
AB  - OBJECTIVE: In recent years, gains in neonatal survival have been most evident
      among very low birth weight, preterm, and low birth weight (LBW) infants. Most of
      the improvement in neonatal survival since the early 1980s seems to be the
      consequence of decreasing birth weight-specific mortality rates, which occurred
      during a period of increasing preterm and LBW rates. Although the decline in
      neonatal mortality has been widely publicized in the United States, research
      suggests that clinicians may still underestimate the chances of survival of an
      infant who is born too early or too small and may overestimate the eventuality of
      serious disability. So that clinicians may have current and needed ethnic- and
      race-specific estimates of the "chances" of early survival for newborn infants,
      we examined birth weight/gestational age-specific neonatal mortality rates for
      the 3 largest ethnic/racial groups in the United States: non-Hispanic whites,
      Hispanics, and non-Hispanic blacks. Marked racial variation in birth weight and
      gestational age-specific mortality has long been recognized, and growing concerns
      have been raised about ongoing and increasing racial disparities in pregnancy
      outcomes. Our purpose for this investigation was to provide an up-to-date
      national reference for birth weight/gestational age-specific neonatal mortality
      rates for use by clinicians in care decision making and discussions with parents.
      METHODS: The National Center for Health Statistics linked live birth-infant death
      cohort files for 1995-1997 were used for this study. Singleton live births to US
      resident mothers with a reported maternal ethnicity/race of non-Hispanic white,
      non-Hispanic black, or Hispanic (n = 10 610 715) were selected for analysis.
      Birth weight/gestational age-specific neonatal mortality rates were calculated
      using 250 g/2-week intervals for each ethnic/racial group. RESULTS: The overall
      neonatal mortality rates for whites, Hispanics, and blacks were 3.24, 3.45, and
      8.16 neonatal deaths per 1000 live births, and the proportion of births <28 weeks
      was 0.35%, 0.45%, and 1.39%, respectively. Newborns who weighed <1500 g comprised
      <2.5% of all births in each racial/ethnic group but accounted for >50% of
      neonatal deaths. For whites, Hispanics, and blacks, >50% of newborns 24 to 25
      weeks of gestational age survived. For most combinations of birth weights <3500 g
      and gestational ages of <37 weeks, the neonatal mortality rate was lowest among
      blacks, compared with whites or Hispanics. At these same gestational age/birth
      weight combinations, Hispanics have slightly lower mortality rates than whites.
      For combinations of birth weights >3500 g and gestational ages of 37 to 41 weeks,
      Hispanics had the lowest neonatal mortality rate. In these birth
      weight/gestational age combinations, where approximately two thirds of births
      occur, blacks had the highest neonatal mortality rate. CONCLUSIONS: Compared with
      earlier reports, these data suggest that a substantial improvement in birth
      weight/gestational age-specific neonatal mortality has occurred in the United
      States. Regardless of ethnicity/race, the risk of a neonatal death does not
      exceed 50% (the suggested definition for the limit of viability), except for
      birth weights below 500 g and gestational ages <24 weeks. Notwithstanding,
      ethnic/racial variations in neonatal mortality rates continue to persist, both in
      overall rates and within birth weight/gestational age categories. Blacks continue
      to have higher proportions for preterm and LBW births, compared with either
      whites or Hispanics. At the same time, blacks experience lower risks of neonatal
      mortality for preterm and LBW infants, while having higher risks of mortality
      among term, postterm, normal birth weight, and macrosomic births.

PMID- 12509597
TI  - Spiritual care needs of hospitalized children and their families: a national
      survey of pastoral care providers' perceptions.
AB  - OBJECTIVE: Although spirituality is viewed as a vital aspect of the illness
      experience by most Americans, little is known about this domain of pediatric
      health care. The objective of this study was to profile pastoral care providers'
      perceptions of the spiritual care needs of hospitalized children and their
      parents, barriers to better pastoral care, and quality of spiritual care in
      children's hospitals. METHODS: A cross-sectional mail survey was conducted of
      pastoral care providers at children's hospitals throughout the United States,
      with a 67% response rate from 115 institutions. RESULTS: Respondents estimated
      that, among patients they visited, 34% were chronically ill and 21% were clearly
      dying. Half or more of patients were thought to have spiritual care needs
      regarding feeling fearful or anxious, coping with pain or other physical
      symptoms, and regarding their relationship to their parents or the relationship
      between their parents. Among patients' parents, 60% to 80% were estimated to have
      felt fearful or anxious, had difficulty coping with their child's pain or other
      symptoms, sought more medical information about their child's illness, questioned
      why they and their child were going through this experience, asked about the
      meaning or purpose of suffering, and felt guilty. Respondents agreed on 3
      barriers to providing spiritual care: inadequate staffing of the pastoral care
      office, inadequate training of health care providers to detect patients'
      spiritual needs, and being called to visit with patients and families too late to
      provide all the care that could have been provided. Overall, respondents judged
      that their hospitals were providing 60% of what they deemed as ideal spiritual
      care. CONCLUSIONS: Pastoral care providers believe that the spiritual care needs
      of hospitalized children and their parents are diverse and extensive. With system
      level barriers cited as limiting the quality of spiritual care, considerable
      improvement may be possible.

PMID- 12509598
TI  - Slow blood sampling from an umbilical artery catheter prevents a decrease in
      cerebral oxygenation in the preterm newborn.
AB  - OBJECTIVE: Blood sampling from an umbilical artery catheter (UAC) placed in a
      high position (thoracal 6-9) has the potential to produce clinically significant
      changes in cerebral blood flow and, thereby, in cerebral oxygenation. This may
      contribute to cerebral impairment in preterm newborn infants. Therefore, we set
      up a study to determine the effects of different sampling speeds through a UAC on
      cerebral oxygenation in preterm infants. METHODS: Thirty pairs of measurements
      were conducted on 20 preterm infants (median gestational age: 30.14 weeks; median
      birth weight: 1170 g). For each infant, 2 blood samplings (both 2.3 mL, including
      flush volume) through the UAC in high position were taken at 2 different speeds
      (20 and 40 seconds) in alternating sequence. Cerebral oxygenation was measured
      noninvasively by near-infrared spectroscopy. Concentration changes in cerebral
      oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb), along with the
      tissue oxygenation index (TOI; O2Hb/[O2Hb + HHb] x 100), were recorded while
      blood was withdrawn and subsequently reinfused. RESULTS: A significant decrease
      in O2Hb and TOI occurred during blood sampling within 20 seconds (median
      DeltaO2Hb: -1.5 micromol/L; range: -4.1-2.3; median DeltaTOI: -0.6%; range: -6.3
      2.3), whereas HHb increased (median DeltaHHb: 0.4 micromol/L, range: -1.1-3.9).
      No significant change was found in O2Hb, HHb, and TOI when sampling time was
      extended to 40 seconds. CONCLUSION: Our results show that blood withdrawal over
      20 seconds from a UAC in high position significantly decreases cerebral O2Hb and
      TOI in preterm infants. Prolonging sampling time to 40 seconds can prevent this
      phenomenon.

PMID- 12509599
TI  - Low-dose aspirin in pregnancy: maternal and neonatal aspirin concentrations and
      neonatal prostanoid formation.
AB  - OBJECTIVE: To evaluate maternal and neonatal plasma concentrations of
      acetylsalicylic acid and salicylic acid and the neonatal endogenous prostanoid
      formation during low-dose aspirin prophylaxis (LDA; 100 mg daily) in pregnant
      women. METHODS: Concentrations of acetylsalicylic acid and salicylic acid in
      maternal plasma after at least 4 weeks of LDA (n = 14) and in umbilical cord
      plasma of newborns after maternal LDA (n = 7) were determined by gas
      chromatography-mass spectrometry. Platelet and renal formation of thromboxane A2
      and the formation of prostaglandin E2 and prostacyclin were evaluated in vivo by
      quantification of index metabolites in plasma and urine by gas chromatography
      mass spectrometry in neonates after maternal LDA (n = 14) and in a control group.
      RESULTS: In the pregnant women, acetylsalicylic acid and salicylic acid
      concentrations rapidly increased after ingestion of LDA. Acetylsalicylic acid was
      completely eliminated within 4 hours, whereas salicylic acid was detected with
      low concentrations at 18 and 21 hours after dosing. In the neonates,
      acetylsalicylic acid was not detected. Salicylic acid was detected in 1 infant
      only. Platelet thromboxane A2 formation in the newborn infants was significantly
      suppressed but recovered within 2 to 3 days after discontinuation of LDA. Renal
      thromboxane A2 formation and the formation of prostaglandin E2 and prostacyclin
      were not affected by LDA. CONCLUSION: In pregnant women who are treated with LDA,
      acetylsalicylic acid is not completely inactivated in the portal circulation but
      reaches the uteroplacental circulation and exerts antiplatelet effects in the
      fetus and newborn.

PMID- 12509600
TI  - Opisthotonic posturing with neuromuscular irritability attributable to 4
      aminopyridine ingestion by a healthy pediatric patient.
AB  - INTRODUCTION: 4-Aminopyridine (4-AP) is a potassium channel blocker used to
      increase muscle strength in the treatment of demyelinating diseases such as
      multiple sclerosis. We describe a case of ingestion by an 8-month-old child that
      resulted in severe but transient symptoms. CASE REPORT: An 8-month-old boy was
      found with greenish saliva, and a capsule with green 4-AP powder was missing. On
      arrival to an emergency department, he was jittery, tachycardic, and tachypneic.
      Activated charcoal, a cathartic, and midazolam (0.5 mg/kg) were administered
      before transfer to a tertiary pediatric hospital. On arrival, the infant remained
      tachycardic and tachypneic. His eyes deviated upward and he was noted to have 3+
      deep tendon reflexes bilaterally. He was administered 0.9% normal saline (20
      mL/kg) for a wide pulse pressure with low diastolic blood pressure. The patient
      developed dramatic opisthotonic posturing and vermiform tongue fasciculations.
      The symptoms responded well to repeated intravenous doses of benzodiazepines. In
      this case, we used 2 doses of lorazepam (0.05 mg/kg each). During opisthotonic
      posturing, an electroencephalogram performed in the intensive care unit revealed
      no evidence of seizure activity. Within 20 hours after admission, the patient
      became asymptomatic. CONCLUSION: This case is, to our knowledge, the first
      documented pediatric 4-AP ingestion. Clinical signs and symptoms are described as
      well as the response to therapy with benzodiazepines. The electroencephalogram
      performed while the patient was symptomatic was negative for seizures.

PMID- 12509601
TI  - Pyogenic liver abscess and Papillon-Lefevre syndrome: not a rare association.
AB  - Papillon-Lefevre syndrome is a rare, autosomal recessive disease comprising
      palmoplantar keratoderma and periodontitis. Pyogenic liver abscess is an
      increasingly recognized complication. We report a new case of this association
      and review the current literature.

PMID- 12509602
TI  - Classification and definition of disorders causing hypertonia in childhood.
AB  - OBJECTIVE: This report describes the consensus outcome of an interdisciplinary
      workshop that was held at the National Institutes of Health in April 2001. The
      purpose of the workshop and this article are to define the terms "spasticity,"
      "dystonia," and "rigidity" as they are used to describe clinical features of
      hypertonia in children. The definitions presented here are designed to allow
      differentiation of clinical features even when more than 1 is present
      simultaneously. METHODS: A consensus agreement was obtained on the best current
      definitions and their application in clinical situations. RESULTS: "Spasticity"
      is defined as hypertonia in which 1 or both of the following signs are present:
      1) resistance to externally imposed movement increases with increasing speed of
      stretch and varies with the direction of joint movement, and/or 2) resistance to
      externally imposed movement rises rapidly above a threshold speed or joint angle.
      "Dystonia" is defined as a movement disorder in which involuntary sustained or
      intermittent muscle contractions cause twisting and repetitive movements,
      abnormal postures, or both. "Rigidity" is defined as hypertonia in which all of
      the following are true: 1) the resistance to externally imposed joint movement is
      present at very low speeds of movement, does not depend on imposed speed, and
      does not exhibit a speed or angle threshold; 2) simultaneous co-contraction of
      agonists and antagonists may occur, and this is reflected in an immediate
      resistance to a reversal of the direction of movement about a joint; 3) the limb
      does not tend to return toward a particular fixed posture or extreme joint angle;
      and 4) voluntary activity in distant muscle groups does not lead to involuntary
      movements about the rigid joints, although rigidity may worsen. CONCLUSION: We
      have provided a set of definitions for the purpose of identifying different
      components of childhood hypertonia. We encourage the development of clinical
      rating scales that are based on these definitions, and we encourage research to
      relate the degree of hypertonia to the degree of functional ability, change over
      time, and societal participation in children with motor disorders.

PMID- 12509603
TI  - Children and adolescents with eating disorders: the state of the art.
AB  - BACKGROUND: Eating disorders in children and adolescents remain a serious cause
      of morbidity and mortality in children, adolescents, and young adults. The
      working knowledge of pathophysiology, recognition, and management of eating
      disorders continues to evolve as research in this field continues. OBJECTIVES:
      This article builds on previous background and position papers outlining issues
      relevant to the care of the adolescent patient with an eating disorder. METHODS:
      The eating disorder special interest group from the Society for Adolescent
      Medicine recognized the need to update the state of the art published guidelines
      for the care of the adolescent patient with an eating disorder. This article was
      a multidisciplinary, group effort to summarize the current knowledge of best
      practice in the field. RESULTS: This article summarizes newer findings on
      pathogenesis and etiology, prevention and screening, risk factors, nutritional
      issues, care from the primary care clinician's perspective, appropriate use of a
      multidisciplinary team, and issues of managed care and reimbursement.
      CONCLUSIONS: Primary prevention combined with early recognition and treatment
      helps decrease morbidity and mortality in adolescents with eating disorders.

PMID- 12509605
TI  - How to interpret radiological progression in randomized clinical trials?

PMID- 12509606
TI  - The effect of treatment on radiological progression in rheumatoid arthritis: a
      systematic review of randomized placebo-controlled trials.
AB  - OBJECTIVE: To undertake a systematic review of randomized placebo-controlled
      trials to assess and rank the efficacy of pharmacological interventions in
      preventing radiological progression of rheumatoid arthritis. METHODS: The two
      outcome measures were the weighted standardized mean difference and the odds of
      progression of X-ray scores pooled as close to 12 months as possible to minimize
      heterogeneity. RESULTS: A total of 38 trials were identified. Of these, 13 were
      excluded, leaving data on 3907 subjects. Infliximab, cyclosporin, sulphasalazine,
      leflunomide, methotrexate, parenteral gold, corticosteroids, auranofin and
      interleukin 1 receptor antagonist were statistically better than placebo in terms
      of change in erosion scores. All agents were equivalent statistically, with the
      exception of infliximab (which was superior to the last five agents). There were
      similar findings for the odds of progression, with the exception of auranofin
      (P=0.06) and the infliximab-methotrexate comparison (P=0.07). Other agents did
      not reach statistical significance in either outcome measure. With the exception
      of the antimalarials, the magnitude of the effect was consistent with the effect
      seen in short-term disease activity trials. CONCLUSION: There is published
      evidence which supports the efficacy of nine agents in decreasing radiological
      progression in rheumatoid arthritis.

PMID- 12509607
TI  - Down-modulation of chemokine receptor cartilage expression in inflammatory
      arthritis.
AB  - OBJECTIVE: To evaluate in vivo expression of chemokine receptors in cartilage
      tissue samples from healthy and diseased joints. METHODS: Presence and
      distribution of several chemokine receptors in cartilage samples from patients
      with osteoarthritis (OA) or inflammatory arthritis (IA) and from multi-organ
      donors were assessed by immunohistochemistry. The expression of messenger RNA
      (mRNA) for chemokine receptors was also analysed by reverse transcriptase
      polymerase chain reaction (RT-PCR). RESULTS: Normal and OA-affected cartilage
      showed a moderate to high expression of chemokine receptors, while staining of IA
      samples ranged from low to absent. Differences between OA and IA samples were
      present for all receptors but CCR2 and CXCR4. Moreover, mRNAs for CCR1, CCR5 and
      CXCR1 were found both in normal and pathological chondrocytes, suggesting that
      chemokine receptor down-modulation seen in IA samples could be a post
      transcriptional event. CONCLUSION: Data on normal and pathological chondrocytes
      underline the role of chemokines in cartilage homeostasis and suggest an
      imbalance towards catabolic processes in inflammatory conditions.

PMID- 12509608
TI  - Fibrin generated in the synovial fluid activates intimal cells from their apical
      surface: a sequential morphological study in antigen-induced arthritis.
AB  - OBJECTIVE: Fibrin deposits adhered to the synovial surface are typical of
      rheumatoid joints. Since fibrin appears to have a role in arthritis perpetuation
      our aim was to investigate how these deposits are formed and the consequences of
      their adhesion to the tissue. METHODS: The appearance of fibrin aggregates either
      free in the synovial fluid or attached to the membrane was studied in rabbits
      with antigen-induced arthritis by histological techniques at different time
      points from challenge. In the fixed synovial membranes areas of fibrin-bound
      synovium were evaluated by qualitative variables to obtain a sequential profile
      of morphological changes. RESULTS: Fibrin aggregates appeared from the initial
      stages of the disease in the synovial effusion. Later on, they were localized on
      the synovial surface and progressive changes were noted at the fibrin-tissue
      interface, ending with the invasion of the aggregates by synovial cells and their
      incorporation into the tissue. CONCLUSION: Fibrin aggregates generated inside the
      joint cavity may constitute a source of activation and acquisition of
      invasiveness of the synovial fibroblasts, a process to explore within the
      perpetuating mechanisms of rheumatoid arthritis.

PMID- 12509609
TI  - Calculated glomerular filtration rate is a useful screening tool to identify
      scleroderma patients with renal impairment.
AB  - OBJECTIVES: Although it only occurs in a minority of patients, renal involvement
      is a life-threatening complication of scleroderma (SSc). We have investigated the
      utility of two formulae to calculate glomerular filtration rate (GFR) in a
      population of SSc patients. METHODS: Twenty-six patients (20 female, 6 male,
      median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a
      retrospective comparison of measured and calculated GFR. GFR was measured using
      (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the
      Modification of Diet in Renal Disease (MDRD) were used to calculate GFR. RESULTS:
      Eighteen out of 19 patients analysed with a serum creatinine concentration less
      than the upper limit of the normal range had a measured GFR outside the normal
      range. Three patients with a normal creatinine concentration had a measured GFR
      <60 ml/min and in each of these the calculated GFR was also abnormal. All
      patients with a measured GFR <60 ml/min were identified using both the MDRD and
      the modified Cockcroft and Gault formula to calculate GFR. The greatest
      correlation between measured and calculated GFR was seen when the MDRD formula,
      which employs demographic and serum variables, was used in patients with body
      surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the
      Cockcroft and Gault formula to calculate creatinine clearance with a correction
      factor for GFR, the inclusion of patients taking Iloprost and the inclusion of
      patients with BSA <1.4 m(2) were all associated with a lower degree of
      correlation. CONCLUSION: Serum creatinine is a poor marker of renal function in
      SSc patients. Calculating GFR from demographic and serum variables is a simple
      technique to identify SSc patients who have abnormal renal function. The authors
      recommend the use of the MDRD formula.

PMID- 12509610
TI  - Polymyositis as a manifestation of chronic graft-versus-host disease.
AB  - OBJECTIVE: Chronic graft-versus-host disease (GVHD) after haematopoietic stem
      cell transplantation (HSCT) has similarities to some idiopathic autoimmune
      diseases, including polymyositis. To investigate the relationship between chronic
      GVHD and idiopathic myositis we conducted a detailed analysis of all cases of
      myositis occurring in a large series of HSCT patients. METHODS: We conducted a
      retrospective chart review of all cases of myositis that developed in 7161
      patients who underwent HSCT at the Fred Hutchinson Cancer Research Center between
      1969 and 1999. RESULTS: Among 1859 individuals who developed chronic GVHD, 12
      developed myositis. No patients developed myositis without chronic GVHD. Myositis
      was first identified between 7 and 55 months after transplantation. In
      histopathology, electromyography, laboratory values and response to
      immunosuppressive therapy, the cases resembled idiopathic polymyositis.
      Autoantibodies were found in eight cases. CONCLUSIONS: Myositis in the chronic
      GVHD population occurred with an incidence higher than expected by chance,
      suggesting that muscle may be a target tissue for chronic GVHD. Recent studies
      have implicated allogeneic cells persisting after maternal-fetal cell transfer in
      selected autoimmune diseases, including myositis. This report lends support to
      the possibility that both idiopathic myositis and chronic GVHD-related myositis
      could involve allo-autoimmune responses.

PMID- 12509611
TI  - Is thiopurine methyltransferase genetic polymorphism a major factor for
      withdrawal of azathioprine in rheumatoid arthritis patients?
AB  - OBJECTIVE: To determine whether the presence of thiopurine methyltransferase
      (TPMT) alleles associated with reduced or absent activity of thiopurine
      methyltransferase is a major factor for withdrawal of azathioprine (AZA) in
      rheumatoid arthritis (RA) patients. METHODS: The TPMT genotype, including the
      variable number of tandem repeats (VNTR) pattern in the 5' untranslated region,
      was analysed in 111 patients with long-standing RA. Azathioprine (AZA) therapy
      was used in 40 patients (36%) as a disease-modifying anti-rheumatic drug.
      RESULTS: Seven out of 111 RA patients (6.3%) were carriers of a mutant allele,
      TPMT3A (G(460)-->A, A(719)-->G) being the mutant allele observed most frequently.
      In the group of 40 AZA-treated patients, therapy was discontinued in six patients
      because of side-effects and in 26 patients because of lack of efficacy. Three
      patients presented moderate side-effects and were homozygous for the wild-type
      TPMT allele, whereas the remaining three patients, who developed gastrointestinal
      effects with severe nausea and vomiting, were TPMT3A carriers. CONCLUSION: In
      this observational study, the absence of response, probably due to the low-dose
      scheme used, was the major cause of AZA withdrawal in our series of RA patients.
      TPMT genotyping may allow the use of high doses of AZA in patients with normal
      TPMT alleles to improve the efficacy of this immunosuppressive drug. Our data
      support the relationship between gastrointestinal intolerance and thiopurine
      metabolic imbalance.

PMID- 12509612
TI  - Cost-effectiveness of low dose corticosteroids versus non-steroidal anti
      inflammatory drugs and COX-2 specific inhibitors in the long-term treatment of
      rheumatoid arthritis.
AB  - OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are used in nearly
      every patient with rheumatoid arthritis (RA) as part of a comprehensive
      management programme, but their use can be associated with side-effects. Low dose
      corticosteroid (<10 mg/day prednisone) in the treatment of RA is controversial.
      Although it is effective and possibly disease modifying, concerns exist about
      potential adverse events. We assessed costs and health effects of corticosteroids
      compared with NSAIDs and cyclo-oxgenase-2 (COX-2) inhibitors. METHODS: Markov
      (state transition) models were used to simulate a cohort of RA patients taking
      disease-modifying antirheumatic drugs and either corticosteroids or NSAIDs. The
      regimens were assumed to be equally effective for the control of RA. Data on
      incidence, costs and consequences of adverse events from corticosteroids and from
      NSAIDs were taken from the literature. Costs were measured in 1999 US dollars;
      health effects expressed as quality-adjusted life years (QALYs). Sensitivity
      analyses were performed including best-case scenarios (0.5x adverse event rate)
      and worst-case scenarios (1.5x adverse event rate). RESULTS: In the base-case
      analysis corticosteroids were superior to NSAIDs. The sensitivity analyses of
      adverse event rate, using best-case and worst-case scenarios, and age showed that
      the results were sensitive to each combination of adverse event rate and age. In
      contrast, the sensitivity analyses of costs and utilities were robust. Using
      misoprostol or omeprazole prophylaxis with NSAIDs would make corticosteroids cost
      effective. Compared with NSAIDs with COX-2 specific inhibition, corticosteroids
      were still cost-effective. CONCLUSION: Corticosteroids are more cost-effective
      than NSAIDs and COX-2 inhibitors in the long-term treatment of RA.

PMID- 12509613
TI  - Antibody-mediated stripping of CD4 from lymphocyte cell surface in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: Keliximab studies have provided evidence of the therapeutic potential
      of a non-depleting CD4 monoclonal antibody (mAb) in the treatment of rheumatoid
      arthritis (RA). Clenoliximab, an immunoglobulin G4 derivative of keliximab, has
      substantially reduced potential to deplete CD4 cells. In initial studies of
      clenoliximab, we investigated the hypothesis that the decrease in cell surface
      CD4 is the result of antibody-mediated stripping from the cell surface. METHODS:
      Patients received single or multiple intravenous infusions of clenoliximab as
      follows: 0.05, 0.2, 1, 5, 10 or 15 mg/kg (n=3-5/group); 150 or 350 mg weekly x 4;
      or 350 or 700 mg every other week x 2 (n=12/group). Blood was collected for up to
      16 weeks and pharmacokinetic and pharmacodynamic assessments were conducted using
      immunoassay and flow cytometry. RESULTS: CD4 count was largely unaffected by
      clenoliximab treatment. Dose-dependent CD4 coating, down-modulation and stripping
      were observed. Maximal down-modulation persisted for an increasing period as dose
      increased, while soluble CD4-clenoliximab complexes accumulated. The amount of
      CD4 in soluble complex was as much as 20 times the amount of cell-associated CD4.
      For the same total dose, administration of higher doses, less frequently,
      resulted in pharmacodynamic profiles similar to those of lower doses administered
      more frequently. CONCLUSION: Decrease in the density of CD4 on the T-lymphocyte
      surface is caused by antibody-mediated stripping.

PMID- 12509614
TI  - Decrease in serum nucleotide pyrophosphatase activity in ankylosing spondylitis.
AB  - OBJECTIVE: Ankylosing spondylitis (AS) is a prototype of a group of rheumatic
      diseases referred to as spondyloarthropathy. AS patients show marked ectopic
      ossification in the spine, occasionally resulting in so-called bamboo spine.
      Although a strong association with HLA-B27 has been reported, its aetiology
      remains undetermined. Another rheumatic disease, ossification of the posterior
      longitudinal ligament of the spine (OPLL), demonstrates ectopic ossification of
      the spinal ligaments very similar to that of AS. Recently, nucleotide
      pyrophosphatase (NPPS) was implicated in the aetiology of OPLL: an Npps mutation
      was found to cause OPLL in mice, and an association between a polymorphism of the
      human NPPS gene and OPLL was identified. The clinical similarities between AS and
      OPLL led us to hypothesize that NPPS may also be implicated in the aetiology of
      AS. To elucidate the role of NPPS in the pathogenesis of AS, we examined serum
      NPPS activity and the possible association of the NPPS gene with AS. METHODS:
      Forty-four Japanese patients with AS, 43 patients with OPLL, and age- and sex
      matched normal volunteers took part in this study. We determined serum NPPS
      activity using high-performance liquid chromatography and examined the
      association between AS and NPPS using single nucleotide polymorphisms (SNPs) of
      the NPPS gene. RESULTS: Serum NPPS activity in AS patients was significantly
      decreased compared with the controls (P < 0.0001). However, there was no
      association between AS and NPPS gene SNPs. CONCLUSION: NPPS is implicated in the
      pathogenesis of AS.

PMID- 12509615
TI  - The development and evaluation of a drug information leaflet for patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To develop and assess the effectiveness of a drug information leaflet
      (DIL) for D-penicillamine (DPA) and determine whether additional verbal
      information provides enhanced benefit. METHODS: Three preliminary studies were
      undertaken: a reading age study; the development of a DIL for DPA; and a DPA
      knowledge questionnaire. The primary study assessed the effect of the DIL on the
      knowledge of 30 patients at weeks 0 and 24 after commencing DPA. A follow-up
      study of 100 patients randomly assigned to receive the DIL alone (control group)
      or with additional verbal backup (experimental group) determined the effects of
      additional verbal information by comparison of DPA knowledge questionnaire scores
      at weeks 0 and 24. RESULTS: The reading study showed that 12% of the sample had
      difficulty reading and so the DPA DIL was designed to be easy to read using the
      Flesch Reading Index. An assessment of knowledge of DPA prior to reading the DIL
      resulted in scores ranging from 0 to 13 with a median of 2 (maximum possible 14).
      By week 24 the median score was 10 (range 6-14), which was significant at P <
      0.0001. The assessment of additional verbal backup showed that both the control
      group and the experimental group knew little about DPA on study entry, with a
      median score 2 in each group. On study exit, both groups knew significantly more
      (P < 0.001) about the drug; the control group scored 9 and the experimental group
      11 (not significantly different; P=0.109). CONCLUSIONS: A large minority of
      patients have poor reading skills, but when a DIL is designed to be easy to read
      patients gain significant amounts of knowledge from it. Providing additional
      verbal explanations did bring about increases in knowledge but these were not
      significant.

PMID- 12509616
TI  - Mortality and prognostic factors in Spanish patients with systemic sclerosis.
AB  - OBJECTIVE: To determine survival and mortality in a cohort of Spanish patients
      with scleroderma (systemic sclerosis, SSc) and to analyse whether survival is
      influenced by demographic, clinical or immunological variables or the extent of
      skin involvement. METHODS: The study included 79 patients diagnosed with SSc and
      taking part in a study to determine the extent of sclerosis, visceral involvement
      and immunological alterations. We studied the number of observed and expected
      deaths (the expected number being based on age- and sex-specific rates in the
      background population) and derived standardized mortality ratios with their 95%
      confidence intervals (CI). Cumulative survival after onset of the first symptom
      was estimated according to the Kaplan-Meier method. The Cox method was used to
      identify the prognostic factors. RESULTS: The mortality rate was 0.0249 deaths
      per person-year. Survival at 15 yr was 0.62 (95% CI 0.410-0.778). The
      standardized mortality ratio was 429.4% (95% CI 222-750). On crude analysis, lung
      involvement [forced vital capacity (FVC) <70%, pulmonary hypertension], SSc renal
      crisis, an active capillaroscopic pattern, pericardial effusion and age over 60
      yr at diagnosis were associated with shorter survival. On multivariate analysis,
      only age at diagnosis over 60 yr, FVC <70% and SSc renal crisis were independent
      prognostic factors. CONCLUSIONS: The mortality rate associated with SSc showed a
      four-fold increase compared with the background population. Lung involvement and
      sclerodermal renal crisis were found to be independently associated with reduced
      survival.

PMID- 12509617
TI  - Infrared spectroscopy: shedding light on synovitis in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: It is difficult to determine the extent of synovial involvement early
      in the course of rheumatoid arthritis. A spectroscopic technique was used to
      characterize the synovium of the small finger joints in both early and late
      rheumatoid arthritis. This synovium was also compared against normal joints.
      METHODS: Near-infrared spectroscopy assesses the absorption of near-infrared
      light by specific joints, giving a characteristic "fingerprint" of the properties
      of the underlying tissues. Triple measurements by infrared spectroscopy were
      taken at the bilateral second and third metacarpophalangeal joints. Multivariate
      analysis was applied. RESULTS: Analysis was able to demonstrate relationships
      between the specific sources of spectral variation and joint tenderness or
      swelling as well as radiographic damage. Further use of multivariate analysis
      allowed recognition of the spectral patterns seen in early disease vs late
      rheumatoid arthritis and correct classification of over 74% of the joints.
      CONCLUSIONS: The spectral regions where differences occurred were in the
      absorption bands related to tissue oxygenation status, allowing the provocative
      implication that this technique could be detecting ischaemic changes within the
      joint. Near-infrared spectroscopy may thus be able to provide us with some
      information about the biochemical changes associated with synovitis.

PMID- 12509618
TI  - Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid
      arthritis.
AB  - OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3
      (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with
      rheumatoid arthritis (RA). Previous negative reports of their value as predictors
      of joint damage may be due to the lack of a large longitudinal study of early RA
      patients. This study evaluated their use in assessing early untreated patients
      with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients
      with early untreated RA of less than 12 months duration and 20 normal controls
      had baseline serum samples tested with a double-antibody enzyme-linked
      immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen
      score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first
      12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1
      correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49,
      P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32,
      P<0.05) respectively. Analysis of the group of patients with a normal CRP at
      presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the
      presence of erosive disease during the first 12 months (r=0.52 and 0.65
      respectively, P<0.05). Logistic regression analysis, in the patients who were non
      erosive at presentation, showed that the strongest correlation with progression
      in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS:
      Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict
      functional and radiographic outcome in early untreated RA. They may have a
      particular value in predicting the progression of erosive disease in patients who
      are not erosive at presentation.

PMID- 12509619
TI  - The active metabolite of leflunomide, A77 1726, inhibits the production of
      prostaglandin E(2), matrix metalloproteinase 1 and interleukin 6 in human
      fibroblast-like synoviocytes.
AB  - OBJECTIVES: To investigate the effects of the active metabolite of leflunomide,
      A77 1726, on fibroblast-like synoviocytes. In rheumatoid arthritis (RA)
      synoviocytes participate in tissue destruction by producing metalloproteinases
      (MMP), prostaglandin E(2) (PGE(2)) and interleukin (IL) 6, which are involved in
      extracellular matrix degradation, resorption of the mineral phase and osteoclast
      mediated bone resorption. METHODS: Human synoviocytes were stimulated with IL
      1alpha or tumour necrosis factor alpha (TNF-alpha) in the presence of A77 1726.
      Culture supernatants were analysed for production of interstitial collagenase
      (MMP-1), tissue-inhibitor of metalloproteinases 1 (TIMP-1), PGE(2) and IL-6.
      Total RNA was isolated and analysed for steady-state levels of MMP-1,
      cyclooxygenase-2 (COX-2) and IL-6 mRNA. RESULTS: A77 1726 inhibited the
      production of PGE(2) in synoviocytes activated by TNF-alpha and IL-1alpha with
      median inhibitory concentrations (IC(50)) of 7 and 3 microM respectively. In
      contrast, MMP-1 and IL-6 production was inhibited at high A77 1726 concentrations
      (> 10 microM), whereas TIMP-1 was not affected. The inhibition of MMP-1 and IL-6
      production was due to the known inhibitory effect of A77 1726 on pyrimidine
      synthesis, as it was reversed by the addition of uridine. This did not apply to
      PGE(2) production, which was inhibited via direct action of A77 1726 on COX-2, as
      shown by the increasing amount of substrate (arachidonic acid) in the culture
      medium. CONCLUSION: This study shows that some of the beneficial effect of
      leflunomide in RA patients may be due to the inhibition of PGE(2), IL-6 and MMP-1
      production in synoviocytes. This effect, coupled with its multiple inhibitory
      effects on T lymphocyte functions, might account for the significant reduction in
      the rate of disease progression in RA patients treated with leflunomide.

PMID- 12509620
TI  - A controlled pilot study of the utility of mirror visual feedback in the
      treatment of complex regional pain syndrome (type 1).
AB  - BACKGROUND: We assessed mirror visual feedback (MVF) to test the hypothesis that
      incongruence between motor output and sensory input produces complex regional
      pain syndrome (CRPS) (type 1) pain. METHODS: Eight subjects (disease duration >
      or =3 weeks to < or =3 yr) were studied over 6 weeks with assessments including
      two controls (no device and viewing a non-reflective surface) and the
      intervention (MVF). Pain severity and vasomotor changes were recorded. RESULTS:
      The control stages had no analgesic effect. MVF in early CRPS (< or =8 weeks) had
      an immediate analgesic effect and in intermediate disease (< or =1 yr) led to a
      reduction in stiffness. At 6 weeks, normalization of function and thermal
      differences had occurred (early and intermediate disease). No change was found in
      chronic CRPS. CONCLUSIONS: In early CRPS (type 1), visual input from a moving,
      unaffected limb re-establishes the pain-free relationship between sensory
      feedback and motor execution. Trophic changes and a less plastic neural pathway
      preclude this in chronic disease.

PMID- 12509621
TI  - Superior effect of arthroscopic lavage compared with needle aspiration in the
      treatment of inflammatory arthritis of the knee.
AB  - OBJECTIVES: To compare the duration of symptom relief after arthroscopic lavage
      versus needle aspiration in gonarthritis. METHODS: A retrospective chart analysis
      was performed in 50 patients with non-septic inflammatory arthritis of the knee
      who underwent arthroscopic lavage because of relapsing or persisting arthritis
      after needle aspiration. The primary outcome measure was the time until
      symptomatic recurrence of knee synovitis. RESULTS: Needle aspiration was
      associated with a 3.0 times greater risk of recurrence of arthritis compared with
      arthroscopic lavage within 12 months (P<0.001, 95% confidence interval 2.1-4.4).
      Patients with longer disease duration and who had used more disease-modifying
      anti-rheumatic drugs (DMARDs) had a significantly lower risk of recurrence of
      arthritis compared with patients with shorter disease duration and a lower number
      of previous DMARDs (P=0.04 and 0.02 respectively). Corticosteroids augmented the
      effect of both interventions. CONCLUSIONS: Our results indicate that arthroscopic
      lavage is an effective therapeutic modality in the treatment of inflammatory
      arthritis of the knee refractory to joint aspiration, especially in patients with
      longstanding disease.

PMID- 12509622
TI  - Medically unexplained symptoms in patients referred to a specialist rheumatology
      service: prevalence and associations.
AB  - OBJECTIVES: To determine the prevalence of medically unexplained rheumatic
      symptoms amongst patients newly referred to a rheumatology out-patient service
      and to examine their relationship with pain, disability, socioeconomic factors
      and the presence of emotional disorders (anxiety, depression and panic). METHODS:
      A sample of newly referred consecutive patients to a hospital-based, regional
      rheumatology service was administered a questionnaire for assessment of emotional
      disorders, pain, health status and socioeconomic factors. Rheumatologists rated
      the degree to which patients' symptoms were explained by organic disease
      (organicity rating). RESULTS: Two hundred and fifty-six patients were eligible
      and 203 (79%) participated. The sample included 69% females and mean age was 50
      yr. Ninety-three (46%) had symptoms that were completely explained, 52 (26%)
      largely explained, 41 (20%) somewhat explained and 17 (8%) not at all explained
      by organic disease. Patients whose symptoms were of "low organicity" (somewhat or
      not at all explained) were more likely to be female [relative risk (RR) 1.8, 95%
      confidence interval (CI) 1.0-3.1], younger (mean age 44 vs 52 yr, P<0.001) and to
      report more somatic symptoms (median 2 vs 1, P=0.021). On univariate analysis
      they were more likely to be experiencing financial hardship (RR 1.7, 95% CI 1.1
      2.6) and work dissatisfaction (RR 1.6, 95% CI 1.0-2.4) and to live in rented
      housing (RR 1.8, 95% CI 1.2-2.8) or with dependent relatives (RR 1.6, 95% CI 1.0
      2.5). Logistic regression showed that female gender and living in rented housing
      were the significant independent predictors of low organicity. Organicity ratings
      were not associated with pain severity, disability, physical and mental health
      status or the presence of emotional disorders. CONCLUSIONS: Twenty-nine per cent
      of patients newly referred to rheumatology clinics had symptoms that were poorly
      explained by identifiable rheumatic disease. Having unexplained symptoms was
      associated with socioeconomic factors but not levels of pain, disability or
      emotional disorders.

PMID- 12509623
TI  - The inducible nitric oxide synthase promoter polymorphism does not confer
      susceptibility to systemic lupus erythematosus.
AB  - OBJECTIVE: There is increasing evidence that nitric oxide (NO) may be important
      in the pathogenesis of systemic lupus erythematosus (SLE). One possible
      explanation for the differences observed in NO production between SLE patients
      and controls is variation in the 5' promoter region of the NOS2 gene, which
      controls NOS2 transcription. We studied the possible contribution of (CCTTT)(n)
      microsatellite polymorphism in the NOS2 promoter region to susceptibility to SLE
      and the clinical outcome of the disease. METHODS: We analysed the distribution of
      the multiallelic (CCTTT)(n) repeat within the 5' upstream promoter region of the
      NOS2 gene, by a polymerase chain reaction-based method, in 117 SLE patients and
      199 healthy subjects from southern Spain. RESULTS: No statistically significant
      differences between SLE patients and healthy controls were observed with regard
      to the frequency of (CCTTT)(n) microsatellite repeats of any given length.
      Similarly, no associations were found with any of the clinical characteristics
      tested. CONCLUSION: We conclude that polymorphism in the NOS2 gene promoter does
      not play a relevant role in the pathogenesis of SLE in our population.

PMID- 12509624
TI  - Elevated plasma concentrations of nitric oxide, soluble thrombomodulin and
      soluble vascular cell adhesion molecule-1 in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate the correlations among plasma concentrations of nitric
      oxide (NO), soluble thrombomodulin (sTM) and vascular cell adhesion molecule
      (sVCAM-1), and whether these three molecules are associated with renal
      involvement in patients with systemic lupus erythematosus (SLE). METHODS: Plasma
      NO concentrations of 73 SLE patients (35 with renal disease, RSLE patients; 38
      without renal disease, SLE patients) and 28 age- and sex-matched healthy control
      subjects were measured by the non-enzymatic Griess assay, and sTM and sVCAM-1 by
      enzyme-linked immunosorbent assay. RESULTS: In RSLE patients, plasma nitrite
      concentrations were significantly higher than in control subjects (P=0.009) and
      correlated positively with plasma sTM, plasma creatinine and urea (all P<0.05).
      Plasma sTM and sVCAM-1 concentrations were significantly elevated in RSLE and SLE
      patients (both P<0.0001) compared with controls. Plasma sTM was significantly
      correlated with plasma sVCAM-1, and both were correlated with plasma creatinine
      and urea and the SLE Disease Activity Index (all P<0.05). CONCLUSION: Elevated
      plasma NO, sTM, and sVCAM-1 concentrations have significant intercorrelations and
      are strongly associated with renal involvement in SLE.

PMID- 12509625
TI  - Osteoprotegerin expression in synovial tissue from patients with rheumatoid
      arthritis, spondyloarthropathies and osteoarthritis and normal controls.
AB  - OBJECTIVES: To demonstrate the expression of osteoprotegerin (OPG) and receptor
      activator of nuclear factor kappaB ligand (RANKL) in synovial tissue from
      rheumatoid arthritis (RA) patients, establish the cell lineage expressing OPG and
      compare the expression of OPG in RA, spondyloarthropathies, osteoarthritis and
      normal synovial tissue. METHODS: Synovial biopsy specimens were obtained at
      arthroscopy from 16 RA and 12 spondyloarthropathy patients with active synovitis
      of a knee joint, six RA patients with no evidence of active synovitis, 10
      patients with osteoarthritis and 18 normal subjects. Immunohistological analysis
      was performed using monoclonal antibodies (mAb) to detect OPG and RANKL
      expression. In addition, dual immunohistochemical evaluation was performed with
      lineage-specific monoclonal antibodies (macrophages, fibroblasts and endothelial
      cells) and OPG to determine the cell lineages expressing OPG. The sections were
      evaluated by computer-assisted image analysis and semiquantitative analysis.
      RESULTS: Two patterns of OPG expression were seen, one exclusively in endothelial
      cells and one expressed predominantly in macrophages in the synovial lining
      layer. Both patterns of OPG staining could be blocked with excess recombinant
      OPG. Endothelial and synovial lining expression of OPG was seen in all synovial
      tissues except those from patients with active RA. In contrast, RANKL expression
      was seen predominantly in synovial tissue from patients with active disease,
      mainly in sublining regions, particularly within areas of lymphocyte
      infiltration. CONCLUSIONS: OPG expression on macrophage type synovial lining
      cells as well as endothelial cells is deficient in RA patients with active
      synovitis, in contrast to that seen in spondyloarthropathy patients with active
      synovitis. This deficiency in OPG expression in the inflamed joint of RA patients
      may be important in the development of radiologically defined joint erosions.

PMID- 12509626
TI  - Control perceptions in patients with rheumatoid arthritis: the impact of the
      medical consultation.
AB  - OBJECTIVE: To identify factors that patients perceive as influencing control in
      living with the symptoms of rheumatoid arthritis (RA). METHOD: A sample of 40
      patients with RA were recruited randomly from an out-patient population. The
      participants of the sample were interviewed in depth by one researcher to
      identify perceptions of control. They also completed two self-administered
      questionnaires, the Health Assessment Questionnaire and the Rheumatology Attitude
      Index. RESULTS: Four major categories were identified that positively influenced
      perceptions of control in patients living with the consequences of RA. These
      included: (i) the reduction of physical symptoms; (ii) social support matching
      perceived need; (iii) the provision of information; and (iv) the medical
      consultation. Components of the consultation included patient involvement,
      provision of information, feedback and reassurance, empathy and access to an
      expert. CONCLUSION: The categories identified can be influenced by health-care
      professionals in the management of the patient, and if the medical consultation
      is utilized to its full potential it can play a major role in enabling patients
      with RA to manage the daily symptoms of their condition.

PMID- 12509627
TI  - A randomized double-blind pilot study comparing Doloteffin and Vioxx in the
      treatment of low back pain.
AB  - OBJECTIVE: This randomized, double-dummy, double-blind pilot study of acutely
      exacerbated low back pain was aimed to inform a definitive comparison between
      Doloteffin, a proprietary extract of Harpagophytum, and rofecoxib, a selective
      inhibitor of cyclo-oxygenase-2 (COX-2). METHODS: Forty-four patients (phyto-anti
      inflammatory drug-PAID-group) received a daily dose of Doloteffin containing,
      inter alia, 60 mg of harpagoside for 6 weeks and 44 (non-steroidal anti
      inflammatory drug-NSAID-group) received 12.5 mg/day of rofecoxib. All were
      allowed rescue medication of up to 400 mg/day of tramadol. Several outcome
      measures were examined at various intervals to obtain estimates of effect size
      and variability that might be used to decide the most suitable principal outcome
      measure and corresponding numbers required for a definitive study. RESULTS: Forty
      three PAID and 36 NSAID patients completed the study. Ten PAID and 5 NSAID
      patients reported no pain without rescue medication for at least 5 days of the
      6th week of treatment. Eighteen PAID and 12 NSAID patients had more than a 50%
      reduction in the week's average of their pain scores between the 1st and 6th
      weeks. The mean percentage decrease from baseline in the pain component of the
      Arhus Index was 23 (S.D. 52) in PAID and 26 (S.D. 43) in NSAID. The corresponding
      measures for the overall Arhus Index were 11 (31) and 16 (24) and, for the Health
      Assessment Questionnaire, 7 (8) and 6 (7). Tramadol was used by 21 PAID patients
      and 13 NSAID patients. Fourteen patients in each group experienced 39 adverse
      effects, of which 28 (13 in PAID) were judged to some degree attributable to the
      study medications. CONCLUSION: Though no significant intergroup differences were
      demonstrable, large numbers will be needed to show equivalence.

PMID- 12509628
TI  - Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically
      diverse populations.
AB  - INTRODUCTION: IL-10 is an immunoregulatory cytokine which may modulate disease
      expression in rheumatoid arthritis (RA). The IL-10 gene is highly polymorphic
      with a number of single nucleotide polymorphisms in the promoter region and two
      microsatellite loci, IL10.R and IL10.G, 4 kb and 1.1 kb 5' of the transcription
      initiation site. It has been reported that allele 2 of the IL10.R microsatellite
      (IL10.R2) is associated with increased IL-10 secretion and IL10.R3 with reduced
      secretion. Subsequently, over-representation of IL10.R2 and under-representation
      of IL10.R3 in three independent RA groups has been reported. The aim of the
      current study is to determine whether there is an association between the IL10.R2
      allele and RA in two ethnically distinct populations. METHODS: IL10.R genotypes
      were determined by semi-automated DNA sequencing technology in 186 UK Caucasians
      and 138 South Africans of Zulu or Sotho origin, fulfilling the 1987 American
      College of Rheumatology (ACR) criteria for RA. The Caucasian patients had
      relatively severe disease and comprised 75 patients with RA vasculitis, 22 with
      Felty's syndrome and 89 who had undergone a joint replacement (hip or knee)
      within 15 years of the onset of disease. Allele frequencies were compared with
      296 Caucasians and/or 73 South Africans. RESULTS: The frequency of the IL10.R2
      allele was significantly greater in the South Africans (RA and controls) than in
      the Caucasians (0.78 vs 0.66, P=1 x 10(-6)), while the frequency of IL10.R3 was
      less common (0.16 vs 0.3, P=1 x 10(-8)). No differences were observed in either
      IL10.R2 or IL10.R3 frequencies between patients and controls in either
      population. CONCLUSIONS: We were unable to confirm any association between IL10.R
      alleles and RA in this study. However, significant differences were demonstrated
      in the frequency of IL10.R2 and IL10.R3 between the two ethnic groups. The
      relatively high frequency of IL10.R2 in the South African population (0.78) would
      have reduced the power to detect an association with RA.

PMID- 12509629
TI  - Autoantibodies to dsDNA cross-react with the arginine-glycine-rich domain of
      heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) and promote methylation of
      hnRNP A2.
AB  - OBJECTIVE: This study was designed to clarify the internalization of anti-DNA
      antibodies (anti-DNA) into living cells in the pathogenesis of systemic lupus
      erythematosus (SLE) using anti-DNA monoclonal antibodies (mAbs). METHODS: Anti
      DNA mAbs 9D7, 9D7D2, 9A4, 5E3F5, 12B3H2 and 6E11E3 were prepared by a standard
      hybridoma procedure to determine the interaction of anti-DNA with proteins in
      different types of cells. RESULTS: The anti-DNA mAbs reacted with two protein
      antigens (35 and 50 kDa) in the cells. The 35-kDa antigen was shown to have 100%
      homology with hnRNP A2. The arginine-glycine-rich domain in hnRNP A2 was found to
      be the reaction site, and the methylation of hnRNP A2 by PRMT1 (protein arginine
      methyltransferase 1) was increased by anti-DNA. Moreover, anti-DNA was
      demonstrated to bind and internalize into the cytoplasm and nucleus. CONCLUSION:
      Nuclear localizing anti-DNA may cross-react with hnRNP A2 to modulate the
      inflammatory responses and polarize immune reactions associated with SLE.

PMID- 12509630
TI  - Embryonic stem cells injected into the mouse knee joint form teratomas and
      subsequently destroy the joint.
AB  - OBJECTIVE: To determine whether the joint space is a suitable environment for
      embryonic stem (ES) cells to grow and form cartilage. METHOD: We transplanted ES
      cells into the knee joint and a subcutaneous space of mice with severe combined
      immunodeficiency. RESULTS: Teratomas formed in both areas. Those in the joints
      grew and destroyed the joints. The incidence of cartilage formation was the same
      in the knee joint and subcutaneous space, but the ratio of cartilage to teratoma
      was higher in the knee joint than in the subcutaneous space. The teratomas were
      proved to have been derived from the transplanted ES cells by detection of the
      neomycin-resistance gene that had been transfected into the ES cells.
      CONCLUSIONS: It is currently not possible to use ES cells to repair joint
      tissues. Further optimization of donor ES cells to differentiate as well as
      inhibit tumour growth may help to meet these challenges.

PMID- 12509631
TI  - Younger age of onset of gout in Taiwan.
AB  - OBJECTIVE: To study the clinical features of gout in the community and in medical
      centres, and to describe the recent changes in gout in Chinese patients. METHODS:
      We analysed retrospectively the clinical features of 1079 Chinese gout patients
      seen by a rheumatologist between 1993 and 2000. These included 558 patients from
      a private clinic and 521 patients from a medical centre. The data were compared
      with those in previous reports of large Caucasian and non-Caucasian series.
      RESULTS: The mean age of onset was 41.6 yr and the mean disease duration before
      first visit was 4.2 yr. For medical centre patients, the mean age of onset was
      43.0 yr and mean disease duration before the first visit was 4.8 yr. For private
      clinic patients, the mean age of onset was 40.2 yr and mean disease duration
      before the first visit was 3.6 yr. Young patients with gout, with onset before
      age 30, constituted 23.3 and 26.7% of the medical centre and private clinic
      patients respectively. Female patients constituted 10.6 and 5.6% respectively,
      the family history was positive in 27.1 and 28.7%, and urolithiasis occurred in
      11.5 and 10.9%. Tophi were found in 21.1% of medical centre and 12.7% of private
      clinic patients. The mean time from first gouty attack to visible tophi was 6.6
      yr in those who developed tophi. CONCLUSIONS: The age at onset of gout was much
      earlier than in previous reports. Twenty-five per cent of patients had their
      first gouty attack before age 30. The first attack frequently occurred between
      the third and fifth decades (68.2%) rather than between the fourth and sixth
      decades, as reported in previous papers. The incidence of gout in females had
      increased (8.0% of the patients were female) and the incidence of tophi was high
      (16.8%). Besides, our patients had more frequent gouty attacks and the interval
      from the first attack to visible tophi was shorter than in previous reports of
      the disease in Caucasians.

PMID- 12509632
TI  - Non-inherited maternal HLA alleles are associated with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is strongly associated with a series of HLA
      DRB1 alleles that encode a conserved sequence of amino acids ((70)Q/R K/R R A
      A(74)) in the DRbeta1 chain, known as the shared epitope (SE). However 30% of
      patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these
      alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy.
      We undertook a family study to investigate the role of NIMA in RA. METHODS: One
      hundred families, including the RA proband and both parents, were recruited. HLA
      DRB1 genotyping was performed using an allele-specific polymerase chain reaction
      by standard methods. The frequencies of NIMA and non-inherited paternal antigens
      (NIPA) were compared using contingency tables and a two-tailed P test. We then
      reviewed four previously published studies of NIMA in RA and conducted an
      analysis of the combined data RESULTS: We identified 36 families in which the
      proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was
      an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis
      with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers
      (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101
      fathers had a non-inherited SE allele (P=0.03). CONCLUSION: A role for HLA NIMA
      in RA is suggested by these results.

PMID- 12509633
TI  - Changes in rheumatology out-patient workload over 12 years in the South West of
      England.

PMID- 12509634
TI  - The first descriptions of therapeutic arthrocentesis: a historical note.
AB  - The existence of synovial fluid has been known since Hippocratic times. The
      abnormal accumulation of liquid inside the joints has been recognized as the
      proximal cause of rheumatic diseases since humoral theory was the dominant
      paradigm in Occidental medical culture. Although evacuating the excess of the
      abnormal humour was the target of all therapeutic measures taken during this era,
      no mention of arthrocentesis is found in Occidental medical texts until 1652. We
      present two earlier indications of arthrocentesis to treat abnormal accumulation
      of liquid inside the joints. One in the Codex Badianus, an Aztec manuscript
      written in the 16th century, and the other in the Tractado breve de medicina,
      published in Mexico in 1592.

PMID- 12509635
TI  - Two cases of atopic dermatitis associated with autoimmune abnormalities.

PMID- 12509636
TI  - Adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome.

PMID- 12509637
TI  - A rare but important cause for a raised serum creatine kinase concentration: two
      case reports and a literature review.

PMID- 12509638
TI  - Tumour necrosis factor inhibitors: maximizing patient safety.

PMID- 12509639
TI  - Use of patient age and anti-Ro/La antibody status to determine the probability of
      patients with systemic lupus erythematosus and sicca symptoms fulfilling criteria
      for secondary Sjogren's syndrome.

PMID- 12509640
TI  - Successful treatment of systemic sclerosis digital ulcers and pulmonary arterial
      hypertension with endothelin receptor antagonist bosentan.

PMID- 12509641
TI  - Life-threatening reversible bone marrow toxicity in a rheumatoid arthritis
      patient switched from leflunomide to infliximab.

PMID- 12509642
TI  - A comparison of patient information sheets for methotrexate.

PMID- 12509644
TI  - Research evidence and the individual patient.

PMID- 12509645
TI  - Itch: scratching more than the surface.
AB  - In origin, itch can be cutaneous ("pruritoceptive", e.g. dermatitis), neuropathic
      (e.g. multiple sclerosis), neurogenic (e.g. cholestasis), mixed (e.g. uraemia) or
      psychogenic. Although itch of cutaneous origin shares a common neural pathway
      with pain, the afferent C-fibres subserving this type of itch are a functionally
      distinct subset: they respond to histamine, acetylcholine and other pruritogens,
      but are insensitive to mechanical stimuli. Histamine is the main mediator for
      itch in insect bite reactions and in most forms of urticaria, and in these
      circumstances the itch responds well to H(1)-antihistamines. However, in most
      dermatoses and in systemic disease, low-sedative H(1)-antihistamines are
      ineffective. Opioid antagonists relieve itch caused by spinal opioids,
      cholestasis and, possibly, uraemia. Ondansetron relieves itch caused by spinal
      opioids (but not cholestasis and uraemia). Other drug treatments for itch include
      rifampicin, colestyramine and 17-alpha alkyl androgens (cholestasis), thalidomide
      (uraemia), cimetidine and corticosteroids (Hodgkin's lymphoma), paroxetine
      (paraneoplastic itch), aspirin and paroxetine (polycythaemia vera) and
      indometacin (some HIV+ patients). If the remedies specified fail, paroxetine and
      mirtazapine should be considered. Ultraviolet B therapy, particularly narrow-band
      UVB, may be superior to drug treatment for itch in uraemia.

PMID- 12509646
TI  - Diagnosis and management of vertebral artery stenosis.

PMID- 12509647
TI  - Effect of zincum gluconicum nasal gel on the duration and symptom severity of the
      common cold in otherwise healthy adults.
AB  - BACKGROUND: Previous studies suggest that zinc salts may be effective in treating
      the common cold. Since rhinovirus infections occur primarily in the nasal cavity,
      an attempt to arrest the infection at the portal of entry seems logical. AIM: To
      assess the ability of zinc nasal gel to shorten the duration and reduce the
      severity of the common cold in healthy adults. STUDY DESIGN: Randomized, double
      blind, placebo-controlled study. METHODS: Of 1087 patients screened by telephone,
      80 patients were enrolled, all presenting within 24-48 h of the onset of illness.
      They received one dose per nostril of a nasal gel spray containing either 33
      mmol/l zincum gluconicum, or an identical placebo four times daily until their
      symptoms resolved, for a maximum of 10 days. RESULTS: Median duration of cold
      symptoms in the zinc group was significantly shorter than in the placebo group
      (median [IQR] 4.3 days [2.5-5.5] vs. 6 days [5-8.5], p=0.002). Nasal drainage,
      nasal congestion, hoarseness, and sore throat were the symptoms most affected.
      Significant reduction of total symptom scores started from the second day of the
      study. Adverse effects (mainly nasal stinging) were similar in both groups.
      DISCUSSION: Zincum gluconicum nasal gel shortens duration and reduces symptom
      severity of the common cold in healthy adults, when started within 24-48 h of the
      onset of illness.

PMID- 12509648
TI  - Changes in seasonal deaths from myocardial infarction.
AB  - BACKGROUND: Cardiovascular disease is the major contributor to excess morbidity
      and mortality in winter. With the rise in temperatures through global warming,
      and the use of central heating and air conditioning, this seasonal variation may
      be declining. AIM: To study possible changes in seasonal variation in case
      fatality rates of myocardial infarction (MI), in men and women, over a 20-year
      period and compare this with possible environmental influences. DESIGN:
      Retrospective analysis of death certificate and climatological data. METHODS: We
      analysed all monthly death certificate data from Northern Ireland, for death
      caused by MI from 1979 through 1998 (n=68 683). Mortality data were standardized
      to a single reference group for the whole period. Seasonal variation in mortality
      and in environmental variables was described using the cosinor model. RESULTS: A
      total of 29 875 women and 38 808 men died from MI during the 20-year period. A
      significant decrease in mortality from MI was observed in both sexes, accompanied
      by a non-significant decline in the amplitude of the seasonal rhythm over the
      study period. Low temperature was associated with higher mortality rates from MI.
      DISCUSSION: We have documented an overall decline in cardiovascular mortality
      from 1979 to 1998, together with a small but non-significant decrease in seasonal
      variation. While improvements in medical care, lifestyle, housing and diet may
      have contributed to the observed decline in mortality rate, seasonal fluctuations
      remain a significant problem.

PMID- 12509649
TI  - Decreased salivary output in patients with Gaucher disease.
AB  - BACKGROUND: Gaucher disease, the most common sphingolipid storage disease,
      results in accumulation of glucocerebroside in macrophages or "Gaucher cells". In
      a preliminary screening of 109 patients with type I disease, when asked
      specifically about dry mouth, approximately one quarter claimed to suffer from
      this symptom. AIM: To ascertain whether decreased salivary output is a feature of
      Gaucher disease. DESIGN: Prospective case-control study. METHODS: Salivary output
      was measured in 65 adult patients and 65 healthy controls using the Saxon test
      with Hochberg's modification. RESULTS: Mean salivary output was 1.91+/-1.19 g/min
      in the patient group vs. 2.74+/-1.17 g/min in the control group (p<0.001). This
      difference was greater among males. These results were not improved in the
      patients receiving enzyme replacement therapy, which is effective in ameliorating
      most Gaucher-related signs and symptoms. DISCUSSION: Recent studies have
      implicated an association between sicca syndrome and viral hepatitis C infection,
      which may imply an immunological trigger for these findings, but in this specific
      cohort, only three patients were reactive for hepatitis C. Follow-up of patients,
      both untreated and receiving enzyme therapy, is needed to delineate the
      association with salivary hypofunction, and ascertain whether enzyme therapy may
      induce sicca symptoms.

PMID- 12509650
TI  - Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine
      receptors in ulcerative colitis.
AB  - BACKGROUND: Ulcerative colitis (UC) is a disease largely of non-smokers, in which
      nicotine is of therapeutic value. The mode of action is unknown, but may involve
      nicotinic acetylcholine receptors (nAChRs) in the bowel wall. AIM: To investigate
      the presence of nAChRs in rectal mucosa, and the effect of smoking and nicotine
      on their expression. DESIGN: Prospective case-control study. METHODS: In situ
      hybridization (ISH) and immunocytochemistry (ICC) were used to show alpha3 nAChRs
      in colonic mucosa. Rectal mucosa was examined from controls (n=55) and patients
      with inactive UC (n=62), both smokers and non-smokers, by ICC, using two
      antibodies to show the density and distribution of receptors in the mucosa. Non
      smokers with UC (n=43) were given transdermal nicotine or placebo patches for 6
      months, and rectal biopsies, taken before and after treatment, were examined by
      ICC to show nAChRs. RESULTS: In normal colon, ISH and ICC showed alpha3 subunit
      in a wide variety of cells, including mucosal epithelium. In rectal biopsies,
      neither smoking nor nicotine influenced the expression of alpha3 immunoreactivity
      in epithelium, either in controls or UC. However, controls had a significantly
      greater density of immunodetectable mucosal epithelium alpha3 subunit, compared
      with UC patients. DISCUSSION: The presence of nAChRs in colonic epithelium may be
      pertinent to the beneficial effect of nicotine in UC, but since neither smoking
      nor nicotine treatment is associated with any change in the expression of
      epithelial alpha3 nAChRs, the effect may be due to functional changes in the
      receptor. The decreased number of alpha3 nAChRs in UC compared with controls may
      be related to an increased cell turnover in UC.

PMID- 12509651
TI  - The prognostic value of the components of the Glasgow Coma Scale following acute
      stroke.
AB  - BACKGROUND: The Glasgow Coma Scale (GCS) is widely used in assessing level of
      consciousness. The GCS verbal component may be misleading in acute stroke: a
      focal neurological deficit leading to dysphasia could affect the score,
      independently of level of consciousness. AIM: To investigate the relationship, in
      all strokes and in dysphasic patients, between stroke outcome and total GCS (with
      and without the verbal score) and its components, to assess their relative
      values. STUDY DESIGN: Retrospective analysis following prospective data
      collection in an acute stroke unit and follow-up. METHODS: Outcomes studied were
      2-week mortality and 3-month recovery (survival, subject living at home). We used
      area under the receiver operating characteristic curve (AUC) to compare versions
      of the GCS and multivariate logistic regression to identify which subset of GCS
      components best predicted outcome. RESULTS: Of 1517 patients with acute stroke,
      1217 had complete clinical and follow-up data; 349 were dysphasic. Total GCS had
      greater AUC than the GCS without the verbal score, for mortality (all patients
      0.78 vs. 0.76, p=0.021; dysphasics 0.72 vs. 0.71, p=0.52) and recovery (all
      patients 0.71 vs. 0.67, p=0.0001; dysphasics 0.74 vs. 0.70, p=0.055). Verbal and
      eye scores independently provided prognostic information, for each patient group
      and outcome measure. CONCLUSIONS: The GCS contains valuable predictive
      information. Regardless of whether dysphasia is present, the verbal score should
      be assessed since it adds prognostic information to that from the eye component,
      and has greater value than the motor score.

PMID- 12509652
TI  - How are we looking after prostate cancer?

PMID- 12509653
TI  - Adrenal corticosteroids in Chinese herbal remedies.

PMID- 12509654
TI  - Stroke website and world stroke mailing list.

PMID- 12509655
TI  - Fishy business.

PMID- 12509656
TI  - All doctors are liars.

PMID- 12509657
TI  - Studying evidence-based processes, not practices.

PMID- 12509659
TI  - Highlights of the 2002 Institute on Psychiatric Services.

PMID- 12509660
TI  - Use of a behavioral health web site and service utilization.

PMID- 12509661
TI  - Strengthening the consumer voice in managed care: VI. Initial lessons from
      independent external review.

PMID- 12509662
TI  - Ambivalence codified: California's new outpatient commitment statute.

PMID- 12509663
TI  - Training child and adolescent psychiatrists for systems of care.

PMID- 12509664
TI  - The Support and Family Education (SAFE) program: mental health facts for
      families.
AB  - Although more than half of adults who have a serious and persistent mental
      illness live with their families (1), less than 10 percent of families of
      outpatients with schizophrenia receive support or education (2). Such services
      fail to be provided despite the fact that family participation in well-designed
      psychoeducational programs has been documented as reducing relapse and
      readmission rates, improving involvement and adherence to treatment (3,4), and
      producing positive outcomes for caregivers, including improved morale, better
      knowledge of mental illness, enhanced feelings of empowerment, and reduced worry
      and displeasure about their loved ones (5,6). Moreover, the vast majority of
      mental health providers believe that educating families about mental illness and
      its treatment is very important (7). Why, then, do so few clinicians commit the
      requisite time and energy to providing these effective and much appreciated
      services? There are four sources of obstacles to the adoption of a psychosocial
      treatment innovation such as family psychoeducation. The obstacles stem from the
      psychoeducational program itself (for example, its unfamiliarity and conflicts
      with the existing treatment ideology); the clinicians (lack of training,
      experience, and competence in functioning as "teachers" with families); the host
      agency or institution (countervailing priorities and lack of administrative
      support); and the process of dissemination (lack of knowledgeable consultants or
      enthusiastic "champions" or advocates for family psychoeducation and lack of user
      friendly curricula or program manuals). These obstacles can be overcome when
      practitioners and family members work together as stakeholders in the benefits
      that accrue from ongoing psychoeducation (8). In this month's column, Michelle
      Sherman, Ph.D., presents the family psychoeducation program she created at the
      Oklahoma City Veterans Affairs (VA) Medical Center. Dr. Sherman describes how she
      tailored the intervention to the VA population, thus generating the support not
      only of the clients and their families but also of her fellow clinicians and the
      VA administration. Her work demonstrates that when mental health clinicians
      devote time, energy, and expertise to supporting and educating caregivers,
      significant benefits emerge for both clients and their families.

PMID- 12509665
TI  - A four-year study of enhancing outpatient psychotherapy in managed care.
AB  - OBJECTIVES: This study was a first step in explicitly attempting to open, at
      least partially, the "black box" of specialty managed mental health care by
      examining qualitative as well as quantitative aspects of managed outpatient
      mental health treatment. The Goal Focus Treatment Planning and Outcomes (GFTPO)
      program was studied as an example of a relatively simple, patient-specific,
      structured educational intervention with a modest capacity to affect practice
      patterns and care over time among network clinicians. METHODS: Four years of data
      from an enhanced care management program (N=28,741) designed to facilitate
      focused, goal-oriented, accountable outpatient psychotherapy and appropriate use
      of medications were used to illustrate what was actually done in one large
      national managed behavioral health organization. Random samples of persons from
      seven matched pairs of GFTPO (N=17,752) and non-GFTPO (N=10,989) employer groups
      from 1995 to 1998 were studied in a quasi-experimental design. The effects of
      GFTPO were tested by analyzing samples compared on five measures of outpatient
      psychotherapy: errors in prescribing medication, continuity of therapists, early
      termination of treatment, likelihood of multiple treatment episodes, and the use
      and cost of services. RESULTS: The GFTPO sample showed a lower incidence of
      medication prescribing errors and therapist switching as well as shorter
      treatment episodes in the year after the start of outpatient treatment. No
      differences were observed in the likelihood of early termination or of having
      multiple treatment episodes. Cost savings did not appear to be at the expense of
      quality of care. CONCLUSIONS: It is possible to enhance the potential for
      measuring and influencing the quality of care in large organized systems.

PMID- 12509666
TI  - Two genealogies of supported housing and their implications for outcome
      assessment.
AB  - Drawing on ongoing fieldwork in New York City, the authors distinguish two
      "genealogies," or developmental traditions, of supported housing. "Housing as
      housing" originated in the mental health field to champion normalized, less
      structured alternatives to clinically managed residential programs. "Integrated
      housing development" traces its origins to the movement to combat homelessness by
      preserving and creating affordable housing. The authors detail the distinctive
      premises, guiding concerns, and developmental logic of each lineage, contrasting
      the consumer advocate focus of the first genealogy with the emphasis on housing
      supply of the second. As housing and service investment strategies, the two
      approaches run different risks, speak to distinctive constituencies, and play to
      specific strengths. The authors argue that any attempt to take the measure of
      their success or to assess their comparative value as social investments must go
      beyond client outcome and come to terms with discrepant notions of the social
      good that they represent.

PMID- 12509667
TI  - Combination antipsychotic therapy in clinical practice.
AB  - OBJECTIVE: Surveys have shown that antipsychotic drug combinations are frequently
      prescribed, yet few clinical studies have examined this practice. Experts have
      generally recommended antipsychotic combinations, especially those combining an
      atypical and a conventional antipsychotic, as a measure of last resort. A survey
      of prescribers was conducted to examine why combination antipsychotic therapy is
      being used in outpatient clinical practice. METHODS: Antipsychotic prescribing
      practices in the Department of Veterans Affairs Puget Sound Health System were
      reviewed for a six-month period during 1998-1999. Data on the use of atypical and
      conventional antipsychotics in combination were collected. RESULTS: A total of
      1,794 patients received prescriptions for at least one antipsychotic medication
      during the study period, of which 715 (40 percent) received an atypical agent.
      Ninety-three patients (13 percent) who were treated with an atypical
      antipsychotic received a prescription for combination antipsychotic therapy for
      at least 30 days. In cases in which both a conventional and an atypical agent
      were prescribed, the primary reason given for adding a conventional antipsychotic
      medication was to treat persistent positive symptoms. The primary reason an
      atypical agent was added to a conventional agent was to switch medications to the
      atypical agent; however, a significant number of patients became "stuck" on the
      combination. CONCLUSIONS: The results of this study support previous reports of
      the frequent use of combination antipsychotic therapy in clinical practice.
      Prospective controlled trials are needed to substantiate perceptions that
      combination antipsychotic therapy is clinically beneficial and to provide
      guidelines on when and for whom antipsychotic polypharmacy should be considered.

PMID- 12509668
TI  - Pathways into and through mental health services for children and adolescents.
AB  - OBJECTIVE: This study examined points of entry into the mental health service
      system for children and adolescents as well as patterns of movement through five
      service sectors: specialty mental health services, education, general medicine,
      juvenile justice, and child welfare. METHODS: The data were from the Great Smoky
      Mountains Study, a longitudinal epidemiologic study of mental health problems and
      service use among youths. The sample consisted of 1,420 youths who were nine, 11,
      or 13 years old at study entry. Each youth and a parent were interviewed at
      baseline and every year thereafter about the use of services for mental health
      problems over the three-year study period. RESULTS: Population estimates
      indicated that 54 percent of youths have used mental health services at some time
      during their lives. The education sector was the most common point of entry and
      provider of services across all age groups. The specialty mental health sector
      was the second most common point of entry for youths up to age 13 years, and
      juvenile justice was the second most common point of entry for youths between the
      ages of 14 and 16. Youths who entered the mental health system through the
      specialty mental health sector were the most likely to subsequently receive
      services from other sectors, and those who entered through the education sector
      were the least likely to do so. CONCLUSIONS: The education sector plays a central
      role as a point of entry into the mental health system. Interagency collaboration
      among three primary sectors-education, specialty mental health services, and
      general medicine-is critical to ensuring that youths who are in need of mental
      health care receive appropriate services.

PMID- 12509669
TI  - The New York-New York housing initiative and use of public shelters by persons
      with severe mental illness.
AB  - OBJECTIVE: The study examined changes in the use of shelters in New York City by
      mentally ill persons with a history of homelessness who received housing
      placements through the New York-New York (NY/NY) housing initiative between 1990
      and 1999 and the impact of the initiative on the overall demand for shelter beds
      in the city. METHODS: Computerized service records on housing, shelter use, and
      health care services were linked to create an integrated data set for 3,167
      persons who received NY/NY housing placements, which provided mental health
      services, and for a matched control group of persons with mental illness who used
      shelters but did not receive housing placements. Regression analyses were used to
      assess the relationships between shelter use and receipt of a placement.
      Differences in postplacement shelter use between NY/NY housing recipients and the
      matched control group were then examined at an individual level and a population
      level. RESULTS: Heavy users of the shelter system were more likely to be placed
      in NY/NY housing. In the two-year postplacement period, persons who received a
      NY/NY housing placement used, on average, 128.2 fewer shelter days than those in
      the control group. In 1996, the NY/NY housing initiative reduced the average
      nightly census in New York City shelters by an estimated 4.6 percent.
      CONCLUSIONS: Providing housing combined with mental health services is an
      effective approach to reducing shelter use among mentally ill persons who have a
      history of homelessness.

PMID- 12509670
TI  - Multiple psychotropic pharmacotherapy among child and adolescent enrollees in
      Connecticut Medicaid managed care.
AB  - OBJECTIVES: The authors sought to determine the prevalence, patterns, and
      demographic correlates of multiple psychotropic pharmacotherapy in a statewide
      sample of low-income children and adolescents in community-based clinical care.
      METHODS: The Medicaid managed care database of the Connecticut Department of
      Social Services was the source of linked encounter and pharmacy information for
      the one-year period ending June 30, 1999. Period prevalence was calculated for
      children and adolescents ranging in age from newborn through 18 years who had any
      psychotropic drug prescription claims during the study period. For each
      participant, multiple psychotropic pharmacotherapy was defined as having claims
      for prescriptions for medications in two or more different psychotropic drug
      classes during a seven-day period. Age, gender, race, and state custody status
      were examined across groups, and multiple psychotropic pharmacotherapy patterns
      were identified. RESULTS: Of the 196,505 youths in Medicaid managed care, 9,447
      received at least one psychotropic medication, yielding a period prevalence of
      4.8 percent. Among youths who received psychotropics, 13.6 percent had received
      multiple psychotropic pharmacotherapy. Multivariate logistic regression revealed
      that participants who received psychotropics, alone or in combination, were
      significantly more likely to be in state custody, male, and older than other
      participants and less likely to be African American or Hispanic. Stimulants,
      antidepressants, and mood stabilizers were the most commonly dispensed agents.
      The most common drug class combinations were an antidepressant plus an
      antipsychotic, a stimulant plus an antidepressant, and a stimulant plus an
      alpha(2) agonist. CONCLUSIONS: Our findings revealed sociodemographic differences
      in psychopharmacological care among young Medicaid managed care enrollees and the
      common occurrence of multiple psychotropic pharmacotherapy.

PMID- 12509671
TI  - Outcomes of homeless adults with mental illness in a housing program and in case
      management only.
AB  - OBJECTIVE: The effectiveness of two types of service programs in ameliorating
      homelessness among individuals with severe mental illness was compared. METHODS:
      Homeless persons with severe mental illness were recruited into the study on
      their entry into one of two types of homeless service programs. The first was a
      comprehensive housing program, in which consumers received guaranteed access to
      housing, housing support services, and case management. The second was a program
      of case management only, in which consumers received specialized case management
      services. In a quasi-experimental or nonrandom-assignment design, participants
      responded to instruments measuring housing status, mental health symptoms,
      substance use, physical health, and quality of life at baseline (program entry)
      and at six months and 12 months after entry. The baseline interview was completed
      by 152 participants and at least one of the two follow-up interviews by 108
      participants. High-, medium-, and low-impairment subgroups, based on psychiatric
      symptoms and degree of alcohol and illegal drug use, were formed by means of a
      propensity score subclassification. RESULTS: Persons with high psychiatric
      symptom severity and high substance use achieved better housing outcomes with the
      comprehensive housing program than with case management alone. However, persons
      with low and medium symptom severity and low levels of alcohol and drug use did
      just as well with case management alone. CONCLUSIONS: The results suggest that
      the effectiveness, and ultimately the cost, of homeless services can be improved
      by matching the type of service to the consumer's level of psychiatric impairment
      and substance use rather than by treating mentally ill homeless persons as a
      homogeneous group.

PMID- 12509672
TI  - Disability compensation seeking among veterans evaluated for posttraumatic stress
      disorder.
AB  - OBJECTIVE: This study sought to further examine the relationship between
      compensation-seeking status and reporting of symptoms among combat veterans who
      were evaluated for posttraumatic stress disorder (PTSD). METHODS: Archival data
      were drawn for 320 adult male combat veterans who were consecutively evaluated at
      a Department of Veterans Affairs (VA) PTSD outpatient clinic from 1995 to 1999.
      The veterans were compared on variables from their clinical evaluation, including
      diagnostic status and self-report measures such as the Minnesota Multiphasic
      Personality Inventory-2, which includes scales designed to detect feigned or
      exaggerated psychopathology. RESULTS: Compensation-seeking veterans reported
      significantly more distress across domains of psychopathology, even after the
      effects of income had been controlled for and despite an absence of differences
      in PTSD diagnoses between groups. However, compensation-seeking veterans also
      were much more likely to overreport or exaggerate their symptoms than were non
      compensation-seeking veterans. CONCLUSIONS: This study provided further evidence
      that VA disability compensation incentives influence the way some veterans report
      their symptoms when they are being evaluated for PTSD. These data suggest that
      current VA disability policies have problematic implications for the delivery of
      clinical care, evaluation of treatment outcome, and rehabilitation efforts within
      the VA.

PMID- 12509673
TI  - Racial differences in the diagnosis of dementia and in its effects on the use and
      costs of health care services.
AB  - OBJECTIVE: This study examined differences in the prevalence of dementia among
      Medicare beneficiaries by race and gender as well as racial differences in the
      effects of dementia on the use and costs of health care services. METHODS: Data
      from a 5 percent random sample of Medicare beneficiaries in the state of
      Tennessee who filed claims between 1991 and 1993 (N=33,680) were analyzed.
      Dementia was assessed on the basis of ICD-9 codes in the billing records of the
      Health Care Financing Administration (HCFA), along with information on gender,
      race, comorbid psychiatric conditions, use of health services, and the actual
      amounts paid by HCFA. Patients with dementia related to Alzheimer's disease were
      excluded. RESULTS: Diagnoses of dementia were significantly more prevalent among
      African-American beneficiaries than among white beneficiaries (5 percent compared
      with 3.9 percent). Persons with dementia had higher rates of health service use,
      particularly for inpatient care, and African-American persons with dementia had
      the highest levels of service use. Health care costs were also significantly
      higher for African Americans with a diagnosis of dementia. Among patients of
      either race, costs were substantially higher among those with comorbid
      psychiatric conditions. CONCLUSIONS: Racial differences in the prevalence of
      dementia are clearly evident. Race also plays a role in the effects of dementia
      on the use and costs of health services, with higher rates of expensive inpatient
      care among African Americans. Racial differences in both the prevalence and costs
      of dementia produce a considerable burden on the health care system. Addressing
      racial disparities in the prevalence of dementia would result in substantial cost
      savings.

PMID- 12509674
TI  - Differences between physical and behavioral health benefits in the health plans
      of at-risk drinkers.
AB  - OBJECTIVE: The goal of this study was to describe the physical and behavioral
      health benefits of a representative community-based sample of at-risk drinkers
      potentially in need of behavioral health services. METHODS: A screening
      instrument for at-risk drinking was administered by telephone to a random
      community sample of more than 12,000 adults. A telephone interview was conducted
      with the health plans of 294 at-risk drinkers who were insured and who consented
      to the release of their insurance records to collect information about supply
      side cost-containment strategies (for example, gatekeeping and restrictions on
      choice of provider), and demand-side cost-containment strategies (for example,
      deductibles, limits, coinsurance, and copayments). Information about health plan
      characteristics was successfully collected for 217 (72 percent) of the insured at
      risk drinkers, representing 113 different health plans and 206 different
      policies. RESULTS: Both provider choice restrictions and gatekeeping were more
      likely to be used for behavioral health care than for physical health care.
      Greater cost-sharing for mental health than for physical health was most often
      achieved by using additional limits (83 percent) and higher coinsurance (66
      percent) and less often achieved by using higher copayments (38 percent) and
      additional deductibles (13 percent). The greater cost-sharing for behavioral
      health amounted to a 30 percent ($42) difference in annual out-of-pocket costs
      for an average user of behavioral health services compared with full parity.
      CONCLUSIONS: The results provide information to advocacy groups and policy makers
      about how much equalization would have to occur in the insurance market before
      full parity could be achieved between physical health and behavioral health
      benefits for a population of individuals potentially in need of behavioral health
      services.

PMID- 12509675
TI  - Perceived coercion at hospital admission and adherence to mental health treatment
      after discharge.
AB  - The authors investigated whether mental health inpatients' perceptions of
      coercion were associated with later treatment adherence. Psychiatric inpatients
      receiving acute care at three sites were interviewed during their hospitalization
      and up to five times after discharge. Patients' perceptions of coercion were
      measured at admission. Adherence to medication and clinical treatment was
      measured every ten weeks for one year after discharge. Among the 825 patients who
      had a perceived coercion score and ten-week follow-up data and who reported that
      outpatient treatment was prescribed, perceived coercion scores were not
      associated with treatment adherence. The authors concluded that perceived
      coercion neither increases nor decreases psychiatric inpatients' medication
      adherence or use of treatment services after discharge.

PMID- 12509676
TI  - The humor group: more than a joke.

PMID- 12509677
TI  - Crisis intervention services in juvenile detention centers.

PMID- 12509679
TI  - The WHO draft manual on mental health legislation.

PMID- 12509678
TI  - The WHO draft manual on mental health legislation.

PMID- 12509682
TI  - Racial bias in the prescription atypical of antipsychotics?

PMID- 12509683
TI  - Use of a psychiatric service dog.

PMID- 12509684
TI  - "Cases" and voices: the changing agenda for doctors and their patients.

PMID- 12509685
TI  - Culyer, research governance, and all that.

PMID- 12509688
TI  - Critical review of unstable angina and non-ST elevation myocardial infarction.
AB  - Within the coronary vasculature the progression of a stable atherosclerotic
      plaque into a vulnerable and ultimately unstable lesion leads to a cascade of
      events culminating in the clinical presentation of unstable angina or acute
      myocardial infarction. In recent years studies have provided new insights in to
      the pathology and natural history, stimulating advances in diagnosis, treatment,
      and management. The review discusses the progress made including the role of
      inflammation, cardiac biomarkers, antiplatelet therapy, and percutaneous
      intervention. Current issues of debate and future directions are also addressed.

PMID- 12509687
TI  - A rational approach to uninvestigated dyspepsia in primary care: review of the
      literature.
AB  - In this paper the rationale and limitations of the four most important approach
      strategies to dyspepsia in primary care (empiric treatment, prompt endoscopy,
      "test-and-scope", and "test-and-treat") are analysed. It is concluded that in the
      absence of alarm symptoms, a "test-and-treat" approach is currently the most
      rational approach provided that three conditions are met: (1) a highly accurate
      test should be used, (2) the prevalence of Helicobacter pylori in the population
      should not be too low, and (3) an effective anti-H pylori regimen should be
      prescribed taking sufficient time to instruct and motivate the patient.

PMID- 12509689
TI  - Monitoring hormone replacement therapy by biochemical markers of bone metabolism
      in menopausal women.
AB  - Biochemical markers of bone metabolism are divided into two groups: formation and
      resorption markers. Bone turnover is a dynamic process, which increases in
      postmenopausal period. Hormone replacement therapy (HRT) can diminish this
      increased bone turnover. Biochemical markers reflect acute changes in bone
      metabolism. Therefore, they may be very useful for the prediction of subsequent
      bone mineral density changes after HRT in menopausal women. Both oral and
      transdermal routes of HRT are efficacious in decreasing the levels of biochemical
      markers. However, markers do not replace bone mineral density measurement.
      Collagen type I cross linked N-telopeptide, collagen type I cross linked C
      telopeptide, and osteocalcin are the most promising markers.

PMID- 12509690
TI  - Shaken baby syndrome.
AB  - Shaken baby syndrome is the most common cause of death or serious neurological
      injury resulting from child abuse. It is specific to infancy, when children have
      unique anatomic features. Subdural and retinal haemorrhages are markers of
      shaking injury. An American radiologist, John Caffey, coined the name whiplash
      shaken infant syndrome in 1974. It was, however, a British neurosurgeon,
      Guthkelch who first described shaking as the cause of subdural haemorrhage in
      infants. Impact was later thought to play a major part in the causation of brain
      damage. Recently improved neuropathology and imaging techniques have established
      the cause of brain injury as hypoxic ischaemic encephalopathy. Diffusion weighted
      magnetic resonance imaging is the most sensitive and specific method of
      confirming a shaking injury. Families of children with subdural haemorrhages
      should be thoroughly investigated by social welfare agencies.

PMID- 12509691
TI  - Management of motor neurone disease.
AB  - Motor neurone disease is a progressive neurodegenerative disorder leading to
      severe disability and death. It is clinically characterised by mixed upper and
      lower motor neurone involvement affecting bulbar, limb, and respiratory
      musculature. Recent guidelines have established diagnostic criteria and defined
      management of the condition. In a proportion of familial amyotrophic lateral
      sclerosis there is a mutation in the gene encoding the enzyme copper/zinc
      superoxide dismutase 1; this has allowed mutation screening and generated
      considerable laboratory based research. The diagnosis must be given with care and
      consideration and close follow up is essential. Management involves a
      multidisciplinary team based in the hospital and the community. Riluzole is the
      only drug shown to have a disease modifying effect and has been approved by the
      National Institute for Clinical Excellence. The essence of care is good
      symptomatic management, including nutritional support with percutaneous
      endoscopic gastrostomy and ventilatory care with non-invasive ventilation.
      Palliative care should be introduced before the terminal stages after careful
      discussion with the patient and carers. Knowledge of this condition has grown
      dramatically recently with a parallel improvement in treatment and ability to
      deal with the most troublesome problems.

PMID- 12509692
TI  - An algorithm for the investigation and management of patients with suspected deep
      venous thrombosis at a district general hospital.
AB  - The aim was to show that clinical assessment and serial Dopplers could be used to
      exclude deep venous thrombosis (DVT), and also that clinical assessment in
      combination with D-dimers could be used to exclude DVT. This was a prospective
      trial. Patients underwent clinical assessment, colour flow Doppler, and D-dimer
      measurement. Patients with an equivocal first Doppler and patients with a
      moderate/high pre-test clinical score had a repeat Doppler. Follow up information
      was obtained to see if further thromboembolism developed. Outcome measures
      included the reliability of the clinical assessment, Doppler, and D-dimer in
      excluding DVT. One hundred and ninety four patients were enrolled. The negative
      predictive value of a low medical pre-test score in excluding DVT was 92%. Eighty
      eight patients underwent D-dimer measurement. The negative predictive value of a
      D-dimer <400 units was 96%. The negative predictive value of a low clinical pre
      test score and D-dimer <400 units was 100%. The negative predictive value of a
      low clinical pre-test score and D-dimer <800 units was 97%. The negative
      predictive value of the combination of a low clinical pre-test score and D-dimer
      <400 units was 100%. Twenty three per cent of patients had a low clinical pre
      test score and D-dimer <400 units. Thus, a DVT could be excluded in 23% of
      referred patients. This information could be used to reduce Doppler requests by
      23%. No patient in whom clinical assessment and serial Dopplers had excluded a
      DVT suffered further thromboembolism on follow up. This study has thus shown that
      a low medical pre-test score and negative Doppler reliably exclude DVT; a low pre
      test score and negative D-dimer would reliably exclude DVT.

PMID- 12509693
TI  - Dorsalis pedis arterial pulse: palpation using a bony landmark.
AB  - INTRODUCTION: The unreliability of the pulse examination of the foot has
      primarily been due to variability of technique between examiners. Whereas the
      groove between the medial malleolus and the Achilles tendon more readily defines
      the location of the posterior tibial pulse, the location of the dorsalis pedis
      pulse remains vague. In this paper a novel method of locating the dorsalis pedis
      pulse by physical examination is described. METHODS: Forty one consecutive
      patients admitted to a general surgery service of a tertiary medical centre
      within a two month period were examined. Using the dorsal most prominence of the
      navicular bone as a landmark, the distance to the dorsalis pedis pulse in
      bilateral lower extremities was measured by palpation and compared to Doppler
      ultrasound. Measurements were confirmed by two separate examiners blinded to each
      others' results. RESULTS: The dorsalis pedis artery was palpable in 78% of
      extremities and present by Doppler ultrasound in 95%. The location of the left
      dorsalis pedis artery was a mean (SD) 9.8 (1.4) mm by palpation and 11.1 (2.1) mm
      by Doppler ultrasound from the dorsal most prominence of the navicular bone. The
      right dorsalis pedis artery was 10.4 (3.4) mm by palpation and 11.5 (0.7) mm from
      the dorsal most prominence of the navicular bone. No significant differences in
      location of the dorsalis pedis artery were observed bilaterally between Doppler
      ultrasound and palpation; No significant differences were observed comparing
      contralateral dorsalis pedis arteries nor any differences between the examiners'
      results. CONCLUSION: The dorsal most prominence of the navicular bone provides a
      bony landmark to readily locate the dorsalis pedis artery. Reliability of the
      examination may be increased as to the patency of the dorsalis pedis artery by
      using this dependable anatomic landmark.

PMID- 12509694
TI  - Guidelines, compliance, and effectiveness: a 12 months' audit in an acute
      district general healthcare trust on the two week rule for suspected colorectal
      cancer.
AB  - OBJECTIVES: The Department of Health had recently introduced guidelines so that
      all suspected colorectal cancer patients could be seen by a specialist within two
      weeks of referral by their general practitioners. The usefulness and practicality
      of such a decision had been questioned. The aims of this study were to measure
      the compliance to the guidelines and evaluate the effectiveness of such
      referrals. METHODS: All patients who were referred to the rapid access colorectal
      clinic between August 2000 and July 2001 were included. SETTINGS: Darlington
      Memorial Hospital and Bishop Auckland General Hospital, both under South Durham
      Health Care Trust, were considered for the study. MEASURES: Date of referral,
      referring practitioner, time of appointment, reasons for referral, and diagnosis.
      RESULTS: A total of 239 referrals were made; 96.2% of patients were given
      appointments within two weeks. Rectal bleed was the commonest (32%) cause for
      referral. Diverticular disease was the most frequent (29%) condition diagnosed.
      Altogether 97.4% of referrals were incomplete and 37.6% did not comply with the
      guidelines. Twenty one colorectal cancers (8.9%) were diagnosed. The early cancer
      detection rate was 4.6%. CONCLUSIONS: This audit showed that compliance to the
      guidelines was associated with a higher cancer detection rate. The majority of
      patients received appointments within two weeks. Contrary to some speculations,
      the number of referrals was not limitless. However a high number of referrals
      failed to adhere to the guidelines. The cancer (particularly early cancer)
      detection rate was disappointingly low. This does not reflect an efficient system
      of referral and potential benefits to patients remain questionable.

PMID- 12509695
TI  - Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour, with
      hypercalcaemic crisis, pre-eclampsia, and renal failure.
AB  - Severe hypercalcaemia during pregnancy is rare and most cases are secondary to
      hyperparathyroidism. This is the first report of a parathyroid hormone related
      protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with
      severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both
      the diagnosis and follow up of our patient and should be considered in the
      diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP
      concentration is a strong indicator of malignancy.

PMID- 12509696
TI  - Rectus sheath haematoma: a new set of diagnostic features.
AB  - Rectus muscle haematoma is a well documented clinical entity, but its diagnosis
      remains elusive. A haematoma within the rectus sheath produces a painful, tender
      swelling that can mimic an intraperitoneal mass with features of an acute
      abdomen. Two patients with rectus haematomas presenting after bouts of prolonged
      coughing are reported. In both cases, clinical features and ultrasound findings
      suggested the presence of intraperitoneal pathology. However, in both cases
      consistent findings in the history and examination pointed towards the diagnosis
      of a rectus haematoma. It is proposed that these simple clinical criteria are
      diagnostic of a rectus sheath haematoma, and can thereby avert an unnecessary
      laparotomy.

PMID- 12509697
TI  - New World leishmaniasis from Spain.
AB  - A 69 year old man living in Spain contracted mucocutaneous leishmaniasis
      involving the nose. The infecting organism was Leishmania infantum, which only
      rarely causes the New World form of the disease. The source of infection was
      probably a neighbour's dog. The patient began treatment with liposomal
      amphotericin B but died of pneumonia two months later.

PMID- 12509698
TI  - Renal involvement in an Anderson-Fabry heterozygote.

PMID- 12509699
TI  - A drowsy breathless man.

PMID- 12509700
TI  - A rare cause of backache in an adult male.

PMID- 12509703
TI  - Chronic unexplained fatigue.

PMID- 12509704
TI  - Use of adrenaline by junior doctors.

PMID- 12509705
TI  - Clinical decision-making: coping with uncertainty.

PMID- 12509706
TI  - Homocysteine and Buerger's disease.

PMID- 12509709
TI  - Cystic fibrosis carrier screening: issues in implementation.

PMID- 12509710
TI  - Research priorities for public health sciences in the postgenomic era.

PMID- 12509711
TI  - Lysosomal storage disorders: diagnostic dilemmas and prospects for therapy.
AB  - PURPOSE: The main purpose of this review is to address some concerns regarding
      the accurate and timely diagnosis of lysosomal storage disorders (LSD). METHODS:
      Using their experience in diagnosing LSD in more than 2500 individuals, the
      authors highlight several diagnostic difficulties and solutions and review the
      latest methods for early diagnosis and treatment. RESULTS: While "classic"
      patients can be accurately diagnosed using relatively simple methods in an
      experienced laboratory, atypical patients require more detailed studies. With a
      few exceptions, almost all LSD can be diagnosed in leukocytes or plasma. Methods
      for screening all newborns without a family history of a LSD have been proposed,
      but such screening may require a large amount of effort for little gain.
      CONCLUSIONS: With effective therapy becoming available for some LSD, early
      diagnosis is critically important. If the goal is to prevent serious
      complications related to the nervous and skeletal systems, earlier diagnosis is
      potentially advantageous. Accurate prognosis and assessing the need for
      aggressive therapy in newly diagnosed patients are problems that need further
      study.

PMID- 12509712
TI  - Diversity of mutations and distribution of single nucleotide polymorphic alleles
      in the human alpha-L-iduronidase (IDUA) gene.
AB  - PURPOSE: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder
      resulting from a deficiency of the lysosomal glycosidase, alpha-L-iduronidase
      (IDUA). Patients with MPS I present with variable clinical manifestations ranging
      from severe to mild. To facilitate studies of phenotype-genotype correlation, the
      authors performed molecular studies to detect mutations in MPS I patients and
      characterize single nucleotide polymorphism (SNP) in the gene. METHODS: Twenty
      two unrelated MPS I patients were subjects for mutation detection using reverse
      transcriptional polymerase chain reaction (RT-PCR) and genomic PCR sequencing.
      Polymorphism analyses were performed on controls by restriction enzyme assays of
      PCR amplicons flanking nine intragenic single nucleotide polymorphic alleles.
      RESULTS: Eleven different mutations including two common mutations (Q70X, W402X),
      five recurrent mutations (D315Y, P533R, R621X, R628X, S633L), and four novel
      mutations (R162I, G208D, 1352delG, 1952del25bp) were identified from MPS I
      patients. Multiple SNP alleles coexisting with the disease-causing mutations were
      detected. Allelic frequencies for nine SNP alleles including A8, A20, Q33H, L118,
      N181, A314, A361T, T388, and T410 were determined. CONCLUSIONS: The results
      provide further evidence for the mutational heterogeneity among MPS I patients
      and point out possible common haplotype structures in the gene.

PMID- 12509713
TI  - Cessation of enzyme replacement therapy in Gaucher disease.
AB  - PURPOSE: Enzyme replacement therapy (ERT) is a promising therapeutic intervention
      for lysosomal storage diseases. Posttranslationally engineered human beta
      glucocerebrosidase (Ceredase/Cerezyme) is commercially available and is the
      standard ERT for Type I Gaucher disease. Cessation of therapy is sometimes
      necessary for personal or financial reasons, but the consequences of
      discontinuation are unknown. This study reports results of discontinuing therapy
      in four patients with Type I Gaucher disease with different genotypes and varying
      degrees of clinical involvement. METHODS: Patient genotypes were as follows:
      N370S/L444P (Patients 1 and 2), K79N/K79N (Patient 3), and N370S/N370S (Patient
      4). All were evaluated before, during, and after withdrawal from ERT. Patients 1,
      2, and 3 were studied after reinstituting ERT. The following parameters were
      documented at 3- to 12-month intervals in all patients: hemoglobin, platelet
      count, angiotensin-converting enzyme, spleen volume, liver volume, femoral
      magnetic resonance imaging, bone density, and urinary pyridinium crosslinks.
      RESULTS: After cessation of therapy, Patients 1, 2, and 3 had more dramatic
      regression in hematological and visceral parameters than Patient 4 and required
      reinstitution of ERT within 2 years. All three patients recovered posttreatment
      status within 4 years of reinstituting ERT. Patient 4 remained stable 6 years
      after cessation of ERT. CONCLUSIONS: Regression of disease status in patients
      with Type I Gaucher disease after cessation of ERT conformed to the genotype
      phenotype relationships of disease onset. Careful monitoring and reinstitution of
      ERT enabled previously attained treatment status.

PMID- 12509714
TI  - Characterization of mutations in 22 females with X-linked dominant
      chondrodysplasia punctata (Happle syndrome).
AB  - PURPOSE: Human X-linked dominant chondrodysplasia punctata (CDPX2) or Happle
      syndrome is associated with mutations in the human emopamil binding protein
      (EBP), a delta8-delta7-sterol isomerase involved in cholesterol biosynthesis. The
      purpose of the current study was to determine the spectrum of EBP mutations in
      females with CDPX2 and the utility of biochemical screening for the disorder by
      analysis of plasma sterols. METHODS: Genomic sequencing of the coding exons of
      the human delta8-delta7-sterol isomerase gene was performed on DNA from 26
      females with suspected X-linked dominant chondrodysplasia punctata. Clinical data
      and sterol analyses were obtained for 24 and 23 of the patients, respectively.
      RESULTS: Mutations in the human EBP delta8-delta7-sterol isomerase gene were
      found in 22 (85%) of 26 females studied, including 20 (91%) of 22 patients who
      demonstrated an abnormal sterol profile. Thirteen of the mutations have not been
      reported previously. All of the females in whom mutations were found demonstrated
      typical skin manifestations of CDPX2, and all but one had a skeletal dysplasia.
      CONCLUSIONS: Plasma sterol analysis was a highly specific and sensitive indicator
      of the presence of an EBP mutation in females with suspected CDPX2, including a
      clinically unaffected mother of a sporadic case. No clear genotype/phenotype
      correlations were ascertained, probably because phenotypic expression is
      influenced substantially by the pattern of X-inactivation in an affected female.

PMID- 12509715
TI  - Asynchronous replication of biallelically expressed loci: a new phenomenon in
      Turner syndrome.
AB  - PURPOSE: Transcriptional activity of genes is related to their replication
      timing; alleles showing the common biallelic mode of expression replicate
      synchronously, whereas those with a monoallelic mode of expression replicate
      asynchronously. Here the level of synchronization in replication timing of
      alleles was determined in subjects with Turner syndrome. METHODS: Fluorescence in
      situ hybridization was used for three loci not linked to X chromosome, in
      lymphocytes derived from 12 controls, 3 individuals with Turner, and 4 with
      mosaic Turner syndrome. RESULTS: In cells derived from controls, each pair of
      alleles replicated synchronously; yet these same alleles replicated
      asynchronously in cells monosomic for X chromosome derived from Turner and mosaic
      Turner patients. When the level of 45,X was low in the mosaic samples, the
      replication pattern of the 46,XX cells was normal. However, in samples with a
      high level of mosaicism, a significantly increased asynchronous replication was
      detected in the 46,XX cells. CONCLUSION: An altered temporal replication control
      in Turner syndrome affecting the aneuploid and euploid cells is shown. This
      alteration may potentially be involved in the determination of the syndrome.

PMID- 12509716
TI  - Prenatal diagnosis from fetal urine in bladder outlet obstruction: success rates
      for traditional cytogenetic evaluation and interphase fluorescence in situ
      hybridization.
AB  - PURPOSE: To determine the optimal approach to the prenatal chromosome analysis of
      fetal urine from fetuses with bladder outlet obstruction. METHODS: Retrospective
      evaluation of traditional cytogenetic and interphase fluorescence in situ
      hybridization (FISH) analysis on fetal urine specimens from fetuses with bladder
      outlet obstruction. RESULTS: Traditional cytogenetic analysis was successful on
      71 (95%) of 75 samples, and FISH was informative on 20 (65%) of 31 specimens. The
      combination of traditional cytogenetic analysis and FISH yielded a 96% diagnostic
      success rate. The mean turnaround time was 8 days (range 5-14) for traditional
      cytogenetic analysis and 1.6 days (range 1.0-4.0) for FISH. Chromosome
      abnormalities were detected in 6 (7.9%) of 76 pregnancies. CONCLUSION:
      Traditional cytogenetic analysis achieves a high success rate (95%) and is
      superior to FISH for chromosome evaluation of fetal urine. However, FISH, when
      informative, can complement traditional cytogenetics as it will expeditiously
      rule out common trisomies in fetuses with bladder outlet obstruction.

PMID- 12509717
TI  - Diagnostic testing for Prader-Willi syndrome and Angelman syndrome: a cost
      comparison.
AB  - PURPOSE: Considering cost as a factor, the authors evaluated three approaches to
      the diagnostic testing of Prader-Willi syndrome (PWS) and Angelman syndrome (AS).
      METHODS: The approaches evaluated were (1) DNA methylation studies followed by
      fluorescence in situ hybridization (FISH) for any positive DNA result, (2) FISH
      analysis followed by DNA testing for any negative result, and (3) simultaneous
      DNA testing and FISH analysis. RESULTS: Of 136 samples submitted for chromosome
      analysis and DNA methylation analysis for PWS or AS, 114 had a normal chromosome
      analysis and methylation studies, 9 were positive for AS, 3 were positive for
      PWS, and 7 had an abnormal chromosome analysis, but not deletion 15q11.2-q13, and
      normal methylation studies. On the basis of these results, the authors compared
      the cost of each testing strategy. CONCLUSION: DNA methylation studies followed
      by confirmation with FISH for any positive result yields a significant cost
      savings compared with the other approaches.

PMID- 12509718
TI  - Incorporating the Contextual Assessment Approach to regimens used in genetic
      family studies.
AB  - PURPOSE: To develop a procedure that enhances enrollment and addresses ethical
      issues associated with participation in genetic family studies. METHODS: The
      Contextual Assessment Approach (CAA) was standardized to the recruitment
      procedures in the Family Investigation of Nephropathy and Diabetes (FIND) study
      at the University of Texas Health Science Center at San Antonio. Structured
      interviews with the CAA questionnaire (CAA-Q) were conducted with 50 low-income
      Mexican-American probands. The CAA allows systematic interpretation of health
      beliefs, family dynamics, and attitudes regarding participation in FIND. Data
      analyses included qualitative and quantitative methods. RESULTS: CAA analyses of
      probands' perspectives regarding relatives' enrollment in FIND facilitated
      recruiting 34 probands from whom 30 families were enrolled (family enrollment
      rate: 88%). CAA reduced recruitment efforts by 32% and avoided exerting undue
      pressure on unwilling participants to ensure voluntary participation. Remarkably,
      76% of the subjects were unaware of any risk associated with participation in
      genetic family studies. CONCLUSIONS: Administering the CAA-Q before enrolling
      subjects in FIND increased our enrollment rate by targeting efforts toward the
      willing subjects and addressing ethical issues associated with their
      participation.

PMID- 12509719
TI  - Cardiac phenotypes in chromosome 4q- syndrome with and without a deletion of the
      dHAND gene.
AB  - PURPOSE: Terminal deletions of chromosome 4q are commonly associated with
      cardiovascular malformations (CVMs). The dHAND gene (HAND2 heart and neural crest
      derivative express 2), a basic helix-loop-helix transcription factor expressed in
      the developing heart, maps to 4q33. A targeted deletion in mouse shows that dHAND
      plays an important role in heart development, suggesting that haploinsufficiency
      of in patients with 4q deletions may be causal for CVMs. The purpose of this
      study is to examine the possible association between dHAND haploinsufficiency
      with the CVMs that occur in patients with 4q terminal deletions. METHODS:
      Fluorescence in situ hybridization (FISH) was performed with a dHAND human
      genomic probe on five patients with terminal deletion at 4q33 or 4q34. RESULTS:
      Of the three patients with a deletion of the dHAND locus, two had CVM (both
      valvar pulmonic stenosis). Of the two patients without a deletion of the dHAND
      gene, one had a small atrial septal defect noted on autopsy. In one of the
      patients with breakpoint on chromosome 4 assigned to 4q34.2 by GTG-banding, FISH
      revealed deletion of the dHAND gene. CONCLUSION: The results suggest that cardiac
      phenotypes are very variable in patients with the terminal deletion of chromosome
      4q and that haploinsufficiency of the dHAND is not necessarily associated with
      CVMs. The correct cytogenetic interpretation of terminal chromosome deletions
      might be augmented by FISH.

PMID- 12509720
TI  - Translational genomics in medical genetics.

PMID- 12509721
TI  - President's message. Elements of success.

PMID- 12509722
TI  - "Just do the best you can".

PMID- 12509724
TI  - Workplace violence and chemical exposure: a 73-year-old CVA patient assaults
      nurses with a fire extinguisher.

PMID- 12509725
TI  - Delays in implementing admission orders for critical care patients associated
      with length of stay in emergency departments in six mid-Atlantic states.
AB  - INTRODUCTION: Every day many admitted patients wait in emergency departments for
      available beds or for a receiving nurse to accomplish a transfer to an inpatient
      bed. The purpose of this study was to examine critical care patients' length of
      stay and time held in the emergency department once admitted to determine if (1)
      holding critical care patients in emergency departments after admission was
      related to skilled nursing shortages and/or limitations in available resources
      and (2) admission orders or tests may have been overlooked during this time.
      Little or no literature exists on this topic. METHODS: A Likert scale survey
      designed to yield descriptive comparative correlational data was sent to
      directors of critical care and emergency service areas. RESULTS: Received
      responses totaled 109. There is a positive correlation between increased length
      of stay and delays in implementation of admission orders while in emergency
      departments and tests missed or delayed upon arrival at the critical care unit. A
      majority of respondents indicated that ED nursing staff had responsibility for
      critical care admitted patients and other patients. Few indicated a formal
      process or committee was in place to address this issue specific to critical care
      patients. Limitations included a convenience sample and variations in operations
      related to size, location, and culture. DISCUSSION: Further study is necessary to
      determine whether patients' length of stay in the hospital is increased because
      of delays in plans of care and if patient outcomes are ultimately affected.

PMID- 12509726
TI  - Stress and coping of Canadian rural nurses caring for trauma patients who are
      transferred out.
AB  - INTRODUCTION: The present study investigated acute stress and coping among rural
      nurses who work with transfer trauma patients. METHODS: Nineteen rural nurses
      ages 34 to 53 years participated in 4 focus groups. Each group was asked to
      identify a specific stressful situation involving transfer of trauma/accident
      patients and to share their experience of the situation. RESULTS: Stressful
      situations encountered included system problems (EG, lack of resources; time
      pressures), lack of communication, visual impact, and professional discord.
      Coping responses included efforts to alter the problem (problem-focused coping)
      and efforts to control emotions (emotion-focused coping). Social support coping
      was identified as the most helpful way of coping with trauma. DISCUSSION: Overall
      the findings suggest that rural nurses face unique stressors not identified in
      the nursing literature, which most often reflects urban settings.

PMID- 12509727
TI  - Developing a successful 16-week "transition ED nursing" program: one busy
      community hospital's experience.

PMID- 12509728
TI  - Terminally ill patients in the emergency department: a practical overview of end
      of-life issues.

PMID- 12509729
TI  - APC billing: an ED manager's primer.

PMID- 12509730
TI  - Acute medical crises masquerading as psychiatric illness.

PMID- 12509731
TI  - The DOG BITES program: documentation of growls and bites in the emergency
      setting.

PMID- 12509732
TI  - Knowledge assessment and preparation for the Certified Emergency Nurses
      examination.

PMID- 12509733
TI  - Miracle of the miners: the Quecreek rescue from an ED perspective.

PMID- 12509734
TI  - An informal discussion of emergency nurses' current clinical practice: what's new
      and what works.

PMID- 12509735
TI  - The threat of terrorism--can our emergency medical systems ever be prepared?

PMID- 12509737
TI  - Multidisciplinary mock trauma code: targeting drinking and driving in the high
      school population.

PMID- 12509741
TI  - The difference between teaching nursing students and registered nurses.

PMID- 12509742
TI  - Emergency nurse practitioners debut in New Zealand.

PMID- 12509743
TI  - Infant botulism in a 10-week-old male: a wolf in sheep's clothing.

PMID- 12509744
TI  - A program to present the realities of alcohol and drug use to fifth, sixth, and
      seventh graders.

PMID- 12509745
TI  - Shareholder activism and health policies.

PMID- 12509746
TI  - So you're going to precept a nursing student: one instructor's suggestions.

PMID- 12509747
TI  - Do SANE examinations satisfy the EMTALA requirement for "medical screening"?
      Sexual assault nurse examiners. Emergency Medical Treatment and Active Labor Act.

PMID- 12509748
TI  - A patient with transmediastinal gunshot wound.

PMID- 12509749
TI  - Protozomics: trypanosomatid parasite genetics comes of age.
AB  - Trypanosomatid protozoans cause important diseases of humans and their domestic
      livestock. Various molecular genetic tools are now allowing rapid progress in
      understanding many of the unique aspects of the molecular and cell biology of
      these organisms. Diploidy and the lack or difficulty of sexual crossing has been
      a challenge for forward genetics, but powerful selections and functional
      complementation have helped to overcome it in Leishmania. RNA interference has
      been adapted for forward genetics in trypanosomes, in which it is also a powerful
      tool for reverse genetics. Interestingly, the efficacy of different genetic tools
      has steered research into different aspects of the biology of these parasites.

PMID- 12509750
TI  - Sequencing the chimpanzee genome: insights into human evolution and disease.
AB  - Large-scale sequencing of the chimpanzee genome is now imminent. Beyond the
      inherent fascination of comparing the sequence of the human genome with that of
      our closest living relative, this project is likely to yield tangible scientific
      benefits in two areas. First, the discovery of functionally important mutations
      that are specific to the human lineage offers a new path towards medical
      benefits. Second, chimpanzee-human comparisons are likely to yield molecular
      insights into how new biological characteristics evolve--findings that might be
      relevant throughout the tree of life.

PMID- 12509751
TI  - Exploring plant genomes by RNA-induced gene silencing.
AB  - The nucleotide sequences of several animal, plant and bacterial genomes are now
      known, but the functions of many of the proteins that they are predicted to
      encode remain unclear. RNA interference is a gene-silencing technology that is
      being used successfully to investigate gene function in several organisms--for
      example, Caenorhabditis elegans. We discuss here that RNA-induced gene silencing
      approaches are also likely to be effective for investigating plant gene function
      in a high-throughput, genome-wide manner.

PMID- 12509752
TI  - The evolution of signalling pathways in animal development.
AB  - Despite the bewildering number of cell types and patterns found in the animal
      kingdom, only a few signalling pathways are required to generate them. Most cell
      cell interactions during embryonic development involve the Hedgehog, Wnt,
      transforming growth factor-beta, receptor tyrosine kinase, Notch, JAK/STAT and
      nuclear hormone pathways. Looking at how these pathways evolved might provide
      insights into how a few signalling pathways can generate so much cellular and
      morphological diversity during the development of individual organisms and the
      evolution of animal body plans.

PMID- 12509753
TI  - The evolutionary genomics of pathogen recombination.
AB  - A pressing problem in studying the evolution of microbial pathogens is to
      determine the extent to which these genomes recombine. This information is
      essential for locating pathogenicity loci by using association studies or
      population genetic approaches. Recombination also complicates the use of
      phylogenetic approaches to estimate evolutionary parameters such as selection
      pressures. Reliable methods that detect and estimate the rate of recombination
      are, therefore, vital. This article reviews the approaches that are available for
      detecting and estimating recombination in microbial pathogens and how they can be
      used to understand pathogen evolution and to identify medically relevant loci.

PMID- 12509754
TI  - Recommendations for introducing genetics services in developing countries.
AB  - Many concerned scientists believe that developments in the medical application of
      genomics will widen the gap between the developed and the developing world. We
      argue that most developing countries now urgently need to incorporate genetic
      approaches (including DNA diagnosis) into their health services, and that many
      are able to do so. DNA diagnosis is relatively inexpensive, helps to develop
      skills in molecular biology and provides a basis for developing national
      expertise in genomics.

PMID- 12509755
TI  - Richard Goldschmidt: hopeful monsters and other 'heresies'.
AB  - Richard Goldschmidt is remembered today as one of the most controversial
      biologists of the twentieth century. Although his work on sex determination and
      physiological genetics earned him accolades from his peers, his rejection of the
      classical gene and his unpopular theories about evolution significantly damaged
      his scientific reputation. This article reviews Goldschmidt's life and work, with
      an emphasis on his controversial views.

PMID- 12509756
TI  - Scientific and therapeutic advances in antiplatelet therapy.
AB  - Over the past decade, the platelet has emerged as a pivotal entity in
      cardiovascular diseases. Indeed, the 'preeminence of the platelet' has spawned a
      variety of drugs that have been shown in large-scale randomized trials to improve
      patient outcomes in acute coronary syndromes and percutaneous revascularization
      procedures. Although the platelet was initially viewed only as a bystander in
      haemostasis, it is now evident that the platelet is in fact a key mediator of
      thrombosis as well as of inflammation. New insights at the cellular and genomic
      levels will probably generate novel drugs to inhibit platelet function more
      effectively and safely than previously possible.

PMID- 12509757
TI  - The emerging field of nanotube biotechnology.
AB  - Nanoparticles are being developed for a host of biomedical and biotechnological
      applications, including drug delivery, enzyme immobilization and DNA
      transfection. Spherical nanoparticles are typically used for such applications,
      which reflects the fact that spheres are easier to make than other shapes. Micro-
      and nanotubes--structures that resemble tiny drinking straws--are alternatives
      that might offer advantages over spherical nanoparticles for some applications.
      This article discusses four approaches for making micro- and nanotubes, and
      reviews the current status of efforts to develop biomedical and biotechnological
      applications of these tubular structures.

PMID- 12509758
TI  - Knockouts model the 100 best-selling drugs--will they model the next 100?
AB  - The biopharmaceutical industry is currently faced with a tremendous number of
      potential drug targets identified through the sequencing of the human genome. The
      challenge ahead is to delineate those targets with the greatest value for
      therapeutic intervention. Here, we critically evaluate mouse-knockout technology
      for target discovery and validation. A retrospective evaluation of the knockout
      phenotypes for the targets of the 100 best-selling drugs indicates that these
      phenotypes correlate well with known drug efficacy, illuminating a productive
      path forward for discovering future drug targets. Prospective mining of the
      druggable genome is being catalysed by large-scale mouse knockout programs
      combined with phenotypic screens focused on identifying targets that modulate
      mammalian physiology in a therapeutically relevant manner.

PMID- 12509759
TI  - Therapeutic antibodies for human diseases at the dawn of the twenty-first
      century.
AB  - Antibodies are highly specific, naturally evolved molecules that recognize and
      eliminate pathogenic and disease antigens. The past 30 years of antibody research
      have hinted at the promise of new versatile therapeutic agents to fight cancer,
      autoimmune diseases and infection. Technology development and the testing of new
      generations of antibody reagents have altered our view of how they might be used
      for prophylactic and therapeutic purposes. The therapeutic antibodies of today
      are genetically engineered molecules that are designed to ensure high specificity
      and functionality. Some antibodies are loaded with toxic modules, whereas others
      are designed to function naturally, depending on the therapeutic application. In
      this review, we discuss various aspects of antibodies that are relevant to their
      use as as therapeutic agents.

PMID- 12509760
TI  - A guide to drug discovery: Target selection in drug discovery.
AB  - Target selection in drug discovery--defined here as the decision to focus on
      finding an agent with a particular biological action that is anticipated to have
      therapeutic utility--is influenced by a complex balance of scientific, medical
      and strategic considerations. In this article, we provide an introduction to the
      key issues in target selection and discuss the rationale for decision making.

PMID- 12509761
TI  - The common technical document: the changing face of the New Drug Application.
AB  - Drug approval is the goal of the long process of drug development. Once
      preclinical and clinical trial data have been collected, a New Drug Application
      must be submitted to the regulatory authority for approval. Although the
      requirements for this submission have similarities around the world, until now,
      the applications have been different. Regulatory authorities working under the
      umbrella of the International Conference on Harmonisation are hoping that the
      development of the Common Technical Document will soon harmonize the application
      procedure, and make this process simpler for applicants.

PMID- 12509762
TI  - The further evolution of biotech.
AB  - Born 20 years ago with the launch of recombinant insulin, the biotechnology
      industry is maturing, with several leading companies now rivalling traditional
      pharmaceutical companies in many ways. What might the next 20 years hold for
      biotech-based drug development?

PMID- 12509763
TI  - Targeting RAS signalling pathways in cancer therapy.
AB  - The RAS proteins control signalling pathways that are key regulators of several
      aspects of normal cell growth and malignant transformation. They are aberrant in
      most human tumours due to activating mutations in the RAS genes themselves or to
      alterations in upstream or downstream signalling components. Rational therapies
      that target the RAS pathways might inhibit tumour growth, survival and spread.
      Several of these new therapeutic agents are showing promise in the clinic and
      many more are being developed.

PMID- 12509764
TI  - The Fanconi anaemia/BRCA pathway.
AB  - Fanconi anaemia (FA) is a rare genetic cancer-susceptibility syndrome that is
      characterized by congenital abnormalities, bone-marrow failure and cellular
      sensitivity to DNA crosslinking agents. Seven FA-associated genes have recently
      been cloned, and their products were found to interact with well-known DNA-damage
      response proteins, including BRCA1, ATM and NBS1. The FA proteins could therefore
      be involved in the cell-cycle checkpoint and DNA-repair pathways. Recent studies
      implicate the FA proteins in the process of repairing chromosome defects that
      occur during homologous recombination, and disruption of the FA genes results in
      chromosome instability--a common feature of many human cancers.

PMID- 12509765
TI  - Targeting tumours with genetically enhanced T lymphocytes.
AB  - The genetic modification of T lymphocytes is an important approach to
      investigating normal T-cell biology and to increasing antitumour immunity. A
      number of genetic strategies aim to increase the recognition of tumour antigens,
      enhance antitumour activities and prevent T-cell malfunction. T cells can also be
      engineered to increase safety, as well as to express markers that can be tracked
      by non-invasive imaging technologies. Genetically modified T cells are therefore
      proving to be of great value for basic immunology and experimental immunotherapy.

PMID- 12509766
TI  - Validating survivin as a cancer therapeutic target.
AB  - Acquisition of the ability to evade cellular suicide, or apoptosis, is one of the
      master switches that contributes to cellular transformation and, ultimately, to
      invasive cancer. Much has been learned about the molecular organization of
      apoptotic pathways and their regulators, but the identification and validation of
      translational targets for apoptosis-based cancer therapy has posed a great
      challenge. Survivin is an attractive candidate for cancer therapy, so what is its
      potential applicability in the clinic?

PMID- 12509767
TI  - Metastasis suppressors alter the signal transduction of cancer cells.
AB  - Tumour metastasis is a significant contributor to death in cancer patients. Eight
      metastasis-suppressor genes that reduce the metastatic propensity of a cancer
      cell line in vivo without affecting its tumorigenicity have been identified.
      These affect important signal-transduction pathways, including mitogen-activated
      protein kinases, RHO, RAC and G-protein-coupled and tyrosine-kinase receptors. So
      how might we use this knowledge to improve the treatment of patients with cancer?

PMID- 12509768
TI  - Screening for lung cancer: in pursuit of pre-metastatic disease.
AB  - One reason for the high death rate of lung cancer is that tumours are not usually
      detected until the disease is at a late stage, at which point the cancer is non
      curable. Spiral computerized tomography is a highly sensitive imaging method that
      could be used to screen high-risk populations, such as current or former smokers,
      for early-stage tumours. Trials to validate this tool are just underway, but
      beyond the imaging tools, population-based care of pre-metastatic lung cancer
      requires considerable evolution in clinical management approaches. More sensitive
      imaging tools might also provide a window into earlier biology, enabling the
      molecular dynamics of lung cancer progression to be elucidated.

PMID- 12509770
TI  - What's taking so long?

PMID- 12509769
TI  - Tumour banks: well-guarded treasures in the interest of patients.
AB  - In order for the genomics revolution to change how we diagnose, categorize and
      treat cancer, scientists and clinicians must have access to tumour samples. There
      has therefore never been a better time to create banks of tumour tissue.
      Collecting and storing tumour samples and their associated data, however, creates
      numerous methodological, ethical, legal and technical problems. How can we leap
      these hurdles in a responsible manner and still make full use of the wealth of
      information that can be obtained from them?

PMID- 12509771
TI  - Somatic recombination redux.

PMID- 12509772
TI  - Quantitative epigenetics.

PMID- 12509773
TI  - Cre-constructing the heart.

PMID- 12509774
TI  - Cancer's deadly signature.

PMID- 12509776
TI  - Does mapping reveal correlation between gene expression and protein-protein
      interaction?

PMID- 12509778
TI  - Equal partnership to ensure that developing countries benefit from genomics.

PMID- 12509782
TI  - European Union considers banning animal testing for cosmetics.

PMID- 12509783
TI  - Protocol review. In case of investigator burnout...

PMID- 12509784
TI  - Skin ulceration in macaque.

PMID- 12509785
TI  - Biosecurity for animal facilities and associated laboratories.
AB  - Although working with human pathogens and zoonotic agents has always carried a
      certain degree of danger, current events have resulted in an increased focus on
      the subject, including new regulations. The authors discuss a number of risk
      assessment and management activities that animal research facilities should use
      to evaluate strengthen their current programs.

PMID- 12509786
TI  - Disinfectants in laboratory animal science: what are they and who says they work?

PMID- 12509787
TI  - Applying the "3 Rs": training course in surgical techniques.
AB  - As the use of surgical procedures in rodents becomes increasingly common in
      biomedical research, institutions face the challenge of ensuring that personnel
      are properly trained to perform these procedures. The author describes a
      microsurgery training course in use at Columbia University.

PMID- 12509788
TI  - Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene.
AB  - In 1978, Sohar et al. described a strikingly peculiar syndrome in two Israeli
      sisters. These young women responded to environmental temperatures of 18 degrees
      C-7 degrees C with profuse sweating on large segments on their back and chest.
      Both had additional abnormalities, including a high-arched palate, nasal voice,
      depressed nasal bridge, inability to fully extend their elbows, and
      kyphoscoliosis. We have observed this disorder in two Norwegian brothers. Genome
      wide screening in the two families, followed by saturation marker studies and
      linkage analysis, identified a 1.4-Mb homozygous candidate region on chromosome
      19p12. The maximum multipoint LOD score was 4.22. In both families, DNA
      sequencing of 25 genes within the candidate region identified potentially
      deleterious CRLF1 sequence variants that were not found in unaffected control
      individuals. Our findings confirm that the cold-induced sweating syndrome is an
      autosomal recessive disorder that is probably caused by impaired function of the
      CRLF1 gene, and they suggest important developmental functions for human CRLF1.

PMID- 12509789
TI  - Identification of I kappa BL as the second major histocompatibility complex
      linked susceptibility locus for rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a complex
      etiology in which environmental factors within a genetically susceptible host
      maneuver the innate and adaptive arms of the immune system toward recognition of
      autoantigens. This ultimately leads to joint destruction and clinical
      symptomatology. Despite the identification of a number of disease-susceptibility
      regions across the genome, RA's major genetic linkage remains with the major
      histocompatibility complex (MHC), which contains not only the key immune-response
      class I and class II genes but also a host of other loci, some with potential
      immunological relevance. Inside the MHC itself, the sole consistent RA
      association is that with HLA-DRB1, although this does not encode all MHC-related
      susceptibility. Indeed, in a set of Japanese patients with RA and a control
      group, we previously reported the presence of a second RA-susceptibility gene
      within the telomeric human leukocyte antigen (HLA) class III region. Using
      microsatellites, we narrowed the susceptibility region to 70 kb telomeric of the
      TNF cluster, known to harbor four expressed genes (I kappa BL, ATP6G, BAT1, and
      MICB). Here, using numerous single-nucleotide polymorphisms (SNPs) and
      insertion/deletion polymorphisms, we identify the second RA-susceptibility locus
      within the HLA region, as the T allele of SNP 96452 (T/A), in the promoter region
      (position -62) of the I kappa BL gene (P=.0062). This -62T/A SNP disrupts the
      putative binding motif for the transcriptional repressor, delta EF1, and hence
      may influence the transcription of I kappa BL, homologous to I kappa B alpha, the
      latter being a known inhibitor of NF kappa B, which is central to innate
      immunity. Therefore, the MHC may harbor RA genetic determinants affecting the
      innate and adaptive arms of the immune system.

PMID- 12509790
TI  - Anterior cranial base reconstruction using free tissue transfer: changing trends.
AB  - INTRODUCTION: A consecutive series of 135 patients undergoing resection for
      malignant tumors involving the anterior cranial base between 1976 and 1999 was
      reviewed. PATIENT AND METHODS: In the years from 1976-1991, free-tissue transfer
      was used in 5 of 76 or 6.6% of cases, whereas free-tissue reconstruction was used
      in 24 of 59 or 40% of cases in the years 1992-1999. Of those cases reconstructed
      with free-tissue transfer in 1976-1991, 60% (three of five) underwent a complex
      resection defined as involving dura, brain, or more than one major structure
      adjacent to skull base. Of those patients reconstructed with conventional
      (pericranial or pericranial/galeal) pedicled flaps in this time period, 35% (25
      of 71) underwent a complex resection. From 1992-1999, 75% (18 of 24) of patients
      reconstructed with free-tissue transfer received a complex resection, whereas
      only 6% (2 of 35) of patients reconstructed by other means received a complex
      resection. OUTCOMES: For those patients reconstructed by free-tissue transfer,
      there were no instances of flap loss. Comparison of these two time periods was
      notable for a similar patient composition in terms of age, histologic findings,
      and extent of resection. Major complication rates for patients who are
      reconstructed with free-tissue transfer for anterior cranial base resections
      (31%) are similar compared with patients who have been reconstructed with
      conventional pedicled flaps (35%). This was noted despite an increased extent and
      complexity of resection in those patients who underwent free-tissue transfer
      reconstruction (72%) compared with those patients reconstructed by more
      conventional means (26%) p <.001. CONCLUSION: In our institution, the use of
      vascularized, free-tissue transfer has replaced pedicled flaps as the preferred
      modality for reconstructing complex anterior cranial base defects involving
      resection of dura, brain, or multiple major structures adjacent to local skull
      base, including the orbit, palate, and other structures. Complication rates for
      patients reconstructed with free-tissue transfer techniques is similar to those
      patients reconstructed by conventional techniques, despite an increase in
      complexity of resection in this group.

PMID- 12509791
TI  - Elective treatment of the neck in squamous cell carcinoma of the larynx: clinical
      experience.
AB  - BACKGROUND: In head and neck cancer, the best prophylactic treatment for the N0
      neck is a subject of debate. Some authors propose lateral selective lymph node
      dissection (levels II-IV) on the basis of the probability of finding occult
      metastases in those lymph nodes. A more extensive procedure including Vth level
      is considered unnecessary because of the low incidence of metastases in the
      posterior triangle. METHODS: We retrospectively evaluated 346 N0 patients
      affected by laryngeal carcinoma and consecutively treated at the Department of
      Otorhinolaryngology of the Ospedale di Circolo, Varese, Italy. The patients
      underwent elective selective neck dissection (levels II-V) for a total of 602
      dissected heminecks. RESULT: Seventy heminecks (11.6%) were pN+, and in 10 of 70
      cases (14.3%) level V was involved; in 5 of 10 metastases were isolated.
      CONCLUSION: Our retrospective study confirms the probabilistic criteria of the
      incidence of occult metastasis by level in laryngeal cancer. On the basis of our
      data Vth level nodes, although very rarely, 10 of 604 (1.6%), are involved with
      laryngeal cancer. Our approach to routinely dissect Vth level nodes is discussed.

PMID- 12509792
TI  - Psychosocial adjustment in head and neck cancer: the impact of disfigurement,
      gender and social support.
AB  - BACKGROUND: The purpose of this study was to examine the psychosocial impact of
      disfigurement, gender, and social support after surgical treatment of head and
      neck cancer. METHOD: Eighty-two ambulatory head and neck cancer patients, 6
      months or more after treatment and free of active disease were assessed. Ratings
      of disfigurement were obtained using a valid and reliable 9-point scale developed
      for the study. Standardized measures of social support, depressive symptoms, well
      being, and life happiness were used. RESULTS: The sample as a whole displayed
      high levels of life happiness, low levels of depression, and positive feelings of
      well-being. Women demonstrated higher levels of depression and lower life
      happiness; subjects with greater disfigurement were more depressed. Social
      support seemed to buffer the impact of greater levels of disfigurement on well
      being for women but not for men. CONCLUSION: These results suggest that women
      with head and neck cancer who experience low social support and face disfiguring
      treatment are at greatest risk for psychosocial dysfunction.

PMID- 12509793
TI  - Arteria lusoria identified on preoperative CT and nonrecurrent inferior laryngeal
      nerve during thyroidectomy: a retrospective study.
AB  - BACKGROUND: To evaluate surgical identification of nonrecurrence of the inferior
      laryngeal nerve (NRILN) during thyroidectomy in patients with an aberrant
      subclavian artery (a. lusoria) as seen on CT. MATERIAL AND METHODS: The medical
      files of patients treated by thyroidectomy between January 1998-December 2000 (n
      = 583) were retrospectively reviewed for preoperative and postoperative mobility
      of the vocal cords and perioperative identification of NRILN. The available
      preoperative CT studies (n = 163) were reviewed for presence of a. lusoria.
      RESULTS: In five patients, the CT study revealed an a. lusoria (3.16%). In one of
      five of these patients, an NRILN was surgically detected; the overall detection
      rate of NRILN was 0.21%. In one of four patients with nonidentification of this
      nerve during surgery, immediate unilateral and permanent vocal cord paralysis
      were present after surgery. No permanent vocal cord paralysis occurred in any of
      the other patients. CONCLUSION: The identification of a. lusoria should alert the
      radiologist and surgeon that a NRILN is present, allowing an anticipating
      surgical technique, reducing the risk of neural injury.

PMID- 12509794
TI  - Phase 1 trial of combined chemotherapy and reirradiation for recurrent
      unresectable head and neck cancer.
AB  - BACKGROUND: The management of recurrent unresectable head and neck cancer remains
      a challenging problem. Based on the circadian rhythm concept, we sought to
      determine the maximum tolerated dose (MTD) of infusional 5-flourouracil (5-FU),
      hydroxyurea (HU), and reirradiation (RT). METHOD: Bolus 5-FU was escalated from
      300 mg/m(2)/d to a 10-hour infusion beginning at midnight, increased at 150
      mg/m(2)/d increments. HU, 1.5 g, remained constant. Chemotherapy was given on
      weeks 1 and 4. RT was given daily, 2.0 Gy per fraction on weeks 1 and 2 followed
      by a 1-week break, then hyperfractionated weeks 4 and 5, total dose 50 Gy. The
      goal was to deliver a continuous course of RT to 60 Gy after the MTD was
      determined with an additional week of chemotherapy. RESULTS: Six cohorts were
      treated to establish the 5-FU MTD of 900 mg/m(2)/d. The seventh cohort received
      continuous RT and 5-FU, 750 mg/m(2)/d, one dose level below the MTD. Two
      hematologic, three skin, and six mucosal >or= grade 3 toxicities were noted in 7
      of 16 patients. The median survival was 10.2 months and the 1-year survival was
      41%. The median survival for the entire group was 9.4 months, with a 1- and 2
      year survival of 39% and 15%, respectively. CONCLUSION: RT can be given in a
      continuous fashion with concurrent 5-FU and HU. Because radiation sensitization
      should be achievable at nontoxic doses of 5-FU, we recommend 600 mg/m(2)/d in
      phase a II setting.

PMID- 12509795
TI  - Different prognostic indices in 310 patients with tonsillar carcinomas.
AB  - BACKGROUND: Several modifications of the TNM system have been reported as better
      prognostic tools than the original classification in head and neck cancer, but
      none of these modifications has been tested in a large series of tonsillar
      carcinomas. These studies did not examine host and treatment factors as
      predictors in addition to TNM. METHODS: Three hundred and ten consecutively
      untreated patients with squamous cell carcinoma of the tonsillar region admitted
      to the Norwegian Radium Hospital and/or the National Hospital between 1960 and
      1996 were included. RESULTS: The five reported TN-based stage modifications were
      all highly significant predictors of survival. Four clinical variables indicating
      shorter disease-specific survival were identified: age > 60, male gender, total
      radiation dose < 70 Gy, and duration of radiotherapy > 50 days. CONCLUSIONS:
      Earlier reported TNM-based stage modifications are all very useful predictors of
      survival in tonsillar carcinomas. In addition, age, gender, total radiation dose,
      and duration of radiotherapy were important prognostic factors. We propose that
      both host and treatment factors should be tested carefully when building new
      prognostic indices in tonsillar carcinomas.

PMID- 12509796
TI  - Decreased salivary gland function in patients with autoimmune thyroiditis.
AB  - BACKGROUND/AIMS: It has been speculated that impaired salivary flow contributes
      to autoimmune thyroiditis (chronic thyroiditis, Hashimoto's thyroiditis). To test
      this hypothesis, salivary function was measured by quantitative salivary
      scintigraphy in autoimmune thyroiditis patients, as well as in age- and gender
      matched controls for comparison. METHODOLOGY: One hundred and twenty patients
      with an autoimmune thyroiditis history of more than 10 years each and 36 healthy
      controls were enrolled in the study. All the 120 autoimmune thyroiditis patients
      had good blood sugar control. None had autonomic neuropathy. These 120 autoimmune
      thyroiditis patients were separated into two subgroups: group 1, 60 patients with
      xerostomia; and group 2, 60 patients without xerostomia. After intravenous
      injection of 5 mCi Tc-99m pertechnetate, sequential images at 1 min/frame were
      acquired for 30 min. The first- and 15th-minute uptake ratios (UR) were
      calculated from the tracer uptakes in the four major salivary glands over the
      background regions of interest (ROIs). Saliva excretion was stimulated by 1
      tablet of 200 mg ascorbic acid given orally 15 min after injection of the tracer.
      Then, the maximal excretion ratios (ER) of the four major salivary glands after
      sialagogue stimulation were calculated. RESULTS: Impaired salivary function,
      represented by significantly decreased UR and ER values, in autoimmune
      thyroiditis patients with xerostomia was demonstrated in this study. In addition,
      there was a significantly higher prevalence of salivary gland dysfunction in
      group 1 patients than in group 2 patients. CONCLUSIONS: Significantly poorer
      salivary function was found in autoimmune thyroiditis patients with xerostomia
      compared with autoimmune thyroiditis patients without xerostomia and healthy
      controls by means of objective and quantitative salivary scintigraphy.

PMID- 12509797
TI  - The usefulness of fluorine 18-labelled deoxyglucose positron emission tomography
      in the investigation of patients with cervical lymphadenopathy from an unknown
      primary tumor.
AB  - BACKGROUND: The usefulness of fluorine 18-labelled deoxyglucose positron emission
      tomography (PET) in the detection of unknown primary tumor in patients seen with
      malignant cervical lymphadenopathy thought to arise from a head and neck primary
      differs in the published reports to date. To assess the role of PET in this
      scenario in our institution, an audit was performed. METHODS: The records of 21
      patients who met the clinical indication were reviewed. End points were the
      ability of PET to detect an unknown primary tumor and/or distant metastatic
      disease. RESULTS: In 8 of the 21 patients, PET detected a potential primary site,
      although none was unequivocally PET positive. One case was pathologically
      confirmed. In five patients the potential primary site identified on PET could
      not be confirmed: two had negative biopsies, and three had no clinical evolution
      in the PET-suspect area for at least 24 months after the initial study. In the
      remaining two patients, the potential primary site detected by PET was treated
      without biopsy. PET detected additional regional and/or distant disease that had
      not been previously documented in nine cases. CONCLUSIONS: PET did not add
      significantly to the detection of an occult primary tumor in patients who had
      already been comprehensively evaluated by clinical and radiologic investigations.
      It was of substantial benefit, however, in detecting unsuspected distant disease
      in patients with undifferentiated nodal histologic findings and helped in
      delineating regional disease in patients with N2 disease.

PMID- 12509798
TI  - A novel mutation in the SDHD gene in a family with inherited paragangliomas-
      implications of genetic diagnosis for follow up and treatment.
AB  - BACKGROUND: Early detection of paragangliomas (PGs) has been linked to low
      morbidity after surgical resection. Recent identification of causative genes
      (SDHB, SDHC, and SDHD) has made it possible to detect individuals at high risk
      for tumors. METHODS: We identified a three-generation family, with four
      individuals affected with PGs. Because pedigree analysis suggested maternal
      imprinting (the phenotype is present only if inherited through the paternal
      line), the SDHD gene (PGL1) was screened. RESULTS: A novel mutation that causes
      skipping of exon 3 was identified. Ten of the seventeen tested individuals
      carried the mutation. All six clinically unaffected individuals inherited the
      mutation from their mother. Five of them are men, with a 50% risk for affected
      progeny. CONCLUSIONS: To allow early treatment with low morbidity, genetic
      counseling is needed when familial paraganglioma is suspected. Asymptomatic
      carriers should be followed by cervical MRI. In addition, because
      pheochromocytomas may occur, catecholamine excretion can be performed. This
      screening should probably be proposed at 5 to 10 years of age.

PMID- 12509799
TI  - Chemoradiotherapy: emerging treatment improvement strategies.
AB  - BACKGROUND: The use of chemotherapeutic drugs in combination with radiotherapy
      has become a common strategy for the treatment of advanced cancer. Solid evidence
      exists showing that chemotherapy administered during the course of radiotherapy
      (concurrent chemoradiotherapy) increases both local tumor control and patient
      survival in a number of cancer sites, including head and neck cancer. These
      therapy improvements, however, have been achieved at the expense of considerable
      toxicity, which underscores the need for further improvements. METHODS: The
      current status of chemoradiotherapy clinical trials for head and neck cancer and
      research on the emerging treatment improvements were reviewed. A review of
      potential treatment improvement strategies focused on preclinical investigations
      on newer chemotherapeutic agents, notably taxanes and nucleoside analogues, as
      well as on molecular targets such as epidermal growth factor receptor (EGFR) or
      cyclooxygenase-2 (COX-2) enzyme. RESULTS: Concurrent, but not induction (drugs
      given before radiotherapy), chemoradiotherapy improves locoregional tumor control
      and survival benefit in head and neck carcinoma relative to radiotherapy alone.
      In comparison, both concurrent and induction chemoradiotherapy showed therapeutic
      advantage over radiotherapy alone in the treatment of lung cancer. These
      therapeutic improvements were achieved with standard chemotherapeutic drugs, most
      commonly cisplatin-based chemotherapy. Biologically, chemotherapy interacts with
      radiation through a number of mechanisms, including inhibition of cellular
      repair, cell cycle effects, and inhibition of tumor cell regeneration. Potential
      avenues emerged to further improve chemoradiotherapy. One of these involves the
      newer chemotherapeutic agents, taxanes and nucleoside analogues, which in
      preclinical studies exhibited strong tumor radiosensitization and therapeutic
      gain. The clinical benefit of these agents is currently under testing. Another
      approach for improvement of chemoradiotherapy consists of inhibiting molecules
      selectively or preferentially expressed on tumor cells, such as EGFR and COX-2,
      both shown to render cellular resistance to drugs or radiation. Agents that
      selectively inhibit these molecules are becoming available at a rapid rate, and
      many of them have been shown in preclinical testing to be highly effective in
      improving tumor radioresponse or chemoresponse without affecting normal tissues.
      CONCLUSIONS: Concurrent chemoradiotherapy, using standard chemotherapeutic
      agents, has emerged as an effective treatment for advanced cancer, but
      unfortunately at the expense of considerable increase in normal tissue toxicity.
      There are a number of potential emerging treatment strategies to further improve
      chemoradiotherapy. One consists of using newer chemotherapeutic drugs, which in
      preclinical studies are potent enhancers of tumor radioresponse. Another approach
      consists of targeting EGFR or COX-2 with selective inhibitors of these molecules.

PMID- 12509800
TI  - Combined modality treatment of Ewing's sarcoma of the maxilla.
AB  - BACKGROUND: Primary bone sarcomas arising in osseous structures of the head and
      neck are rare. These tumors are often incompletely resected and treated with
      radiotherapy for local control. METHODS: We report a case of a 9-year-old girl
      with a maxillary Ewing's sarcoma. This patient was successfully treated with
      neoadjuvant chemotherapy followed by surgical resection and prosthetic
      reconstruction of the primary site. The surgical approach that was used consisted
      of a subtotal maxillectomy by means of a facial degloving approach, sparing the
      orbital contents and the inferior orbital rim and orbital floor. RESULTS: This
      approach produced excellent cosmetic, functional, and oncologic outcome. The
      patient remains without evidence of disease recurrence more than 4 years after
      surgery. CONCLUSIONS: This case illustrates a novel surgical approach to the
      resection of a maxillary Ewing's sarcoma and highlights the need for a
      multidisciplinary team approach to the management of head and neck sarcomas in
      children.

PMID- 12509801
TI  - Peroxynitrite-induced oligodendrocyte toxicity is not dependent on poly(ADP
      ribose) polymerase activation.
AB  - Oligodendrocyte loss is a characteristic feature of several CNS disorders,
      including multiple sclerosis (MS) and spinal cord injury. However, the mechanisms
      responsible for oligodendrocyte destruction remain undefined. As recent studies
      have implicated peroxynitrite in the pathogenesis of both spinal cord injury and
      MS, we have examined whether peroxynitrite may mediate at least some of the
      oligodendrocyte damage and demyelination observed in these conditions. Primary
      rat oligodendrocytes were exposed to authentic peroxynitrite in vitro and
      assessed for cytotoxicity. Mitochondrial function, measured by the reduction of
      MTT to formazan, and mitochondrial membrane potential were used as indicators of
      cell viability. Cell death was quantitated by measuring either the release of
      lactate dehydrogenase from, or the uptake of propidium iodide into, damaged and
      dying cells. Peroxynitrite dose-dependently reduced the viability of primary
      oligodendrocytes and induced cell death. Furthermore, peroxynitrite significantly
      increased DNA strand breakage and the activity of poly(ADP-ribose) polymerase
      (PARP) in oligodendrocyte cultures. To identify whether PARP activation plays a
      role in peroxynitrite-induced oligodendrocyte toxicity, we examined the effects
      of the PARP inhibitors 3-aminobenzamide (3AB) and 5-iodo-6-amino-1,2-benzopyrone
      (INH(2)BP) on mitochondrial function and cell death in oligodendrocytes. The
      presence of 3AB and INH(2)BP did not protect oligodendrocytes from peroxynitrite
      induced cytotoxicity. However, both compounds significantly reduced PARP activity
      in these cells. Primary oligodendrocytes generated from PARP-deficient mice were
      also highly susceptible to peroxynitrite-induced cell death. Therefore, our
      results show that peroxynitrite exerts cytotoxic effects on oligodendrocytes in
      vitro independently of PARP activation.

PMID- 12509802
TI  - Early oligodendrocyte progenitor cells in the human fetal telencephalon.
AB  - Oligodendrocytes, the myelin-producing cells in the central nervous system,
      represent a large portion of the total number of cells in the human brain. Using
      cell-specific markers and antibodies to ventral homeodomain transcription
      factors, NKX2.1 and DLX2, we show here that a subpopulation of early
      oligodendrocyte progenitor cells (OPCs) in the human telencephalon may originate
      in the ganglionic eminence (GE). DLX2-labeled OPCs form a well-delineated stream
      of cells connecting the GE subventricular zone (SVZ) to the cortical intermediate
      zone through the anterior cortical SVZ. This population of cells is labeled by
      early OPCs markers, PDGFRalpha, Olig1, and NG2, and not with either neuronal,
      astrocyte, or late OPCs markers. Intriguingly, numerous CD68(+)
      microglia/macrophages, nestin(+) neural stem cells, and CD34(+) hematopoietic
      stem cells (HSCs) are also present in both the GE stream and the cortical SVZ.
      These cells could be colabeled with DLX2 as well as early OPCs markers. A
      separate subpopulation of early OPCs, present in the GE and cortical SVZ, did not
      express either DLX2 or CD68. These findings suggest that different subpopulations
      of early OPCs, characterized with different sets of transcription factors and
      cell-specific markers, are present in human forebrain. These subpopulations may
      have different origins; one may originate in the cortical SVZ, while others may
      come from the GE and/or outside the CNS as hematopoietic stem cells.

PMID- 12509803
TI  - Astrocytes selectively enhance N-type calcium current in hippocampal neurons.
AB  - Astrocytes influence neuronal development, synapse formation, and synaptic
      transmission, partly through affecting neuronal calcium signals. In order to
      elucidate the extent to which astrocytes modulate neuronal voltage-gated calcium
      currents, we performed a whole-cell patch clamp analysis of neurons in astrocyte
      deplete and astrocyte-enriched conditions. We demonstrate that hippocampal
      neurons in an astrocyte-enriched environment show augmentation of voltage-gated
      calcium current at 1-3 days in vitro. Further study in pairs of adjacent neurons
      showed that the augmentation in calcium current was dependent on direct contact
      with the astrocyte. Pharmacological analysis demonstrated the augmentation is
      selective for the N-type calcium current, although immunochemical labeling of the
      alpha1(B) subunit of the N-type calcium channel was unchanged. These findings
      show that astrocytes regulate neuronal voltage-gated calcium currents in a
      contact-dependent manner. The specificity of the effect for the N-type calcium
      current at early days in culture has special significance regarding the role of
      astrocytes in hippocampal synaptogenesis.

PMID- 12509804
TI  - Gabaergic signaling mediates the morphological organization of astrocytes in the
      adult rat forebrain.
AB  - Previous studies have provided evidence that the morphological organization of
      immature astrocytes is influenced by the inhibitory neuronal transmitter gamma
      amino-butyric acid (GABA). The present study was designed to determine whether
      the occurrence of differential organization of mature astrocytes throughout
      various regions of the adult brain is related to differential GABAergic
      signaling. For this we first used Western blotting and high-performance liquid
      chromatography to quantify the levels of the astrocytic protein glial fibrillary
      acidic protein (GFAP) and GABA, respectively, within the same tissue punches
      taken from different forebrain regions of the adult rat, as well as
      immunocytochemistry for GFAP, GABA, or glutamate decarboxylase to visualize the
      morphological organization of astrocytes and of GABAergic axons in these regions.
      These data indicate that GFAP and GABA contents are correlated throughout the
      different forebrain regions analyzed, and that the regions containing the highest
      densities in GABAergic terminals are those that contain astrocytes exhibiting the
      highest degree of stellation. Secondly, we chronically increased GABAergic
      signaling in vivo by the systemic administration of an inhibitor of GABA
      transaminase or by the intracerebroventricular infusion of muscimol, a potent
      agonist of GABA(A) receptors. Our data show that in both cases, the GFAP content
      of the different forebrain regions is significantly augmented, in close
      association with a marked increase in the number of astrocytic processes and with
      their degree of branching. Taken together, these data strongly suggest that
      GABAergic signaling mediates the morphological organization of astrocytes and
      their expression of GFAP in the adult brain.

PMID- 12509805
TI  - Cytokine-stimulated inducible nitric oxide synthase expression in astroglia: role
      of Erk mitogen-activated protein kinase and NF-kappaB.
AB  - Expression of inducible nitric oxide synthase (iNOS), which leads to the
      production of nitric oxide (NO), is stimulated by proinflammatory cytokines such
      as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Here
      we report on the roles of nuclear factor-kappaB (NF-kappaB) and mitogen-activated
      protein (MAP) kinases in IL-1beta/TNF-alpha-induced iNOS expression in adult rat
      astroglia. Cytokine-induced increases in nitrite accumulation (an index of NO
      production) and iNOS expression were attenuated by inhibition of NF-kappaB with
      pyrrolidine dithiocarbamate (PDTC). Similar attenuation of these cytokine-induced
      responses was produced by inhibition of MAP kinase (MEK), the immediate upstream
      activator of Erk, using PD098,059. Combined treatment of astroglia with PDTC and
      PD098,059 completely abolished the cytokine-induced increases in iNOS expression
      and nitrite accumulation. By contrast, the selective p38 kinase inhibitor
      SB203,580 amplified the effects of IL-1beta/TNF-alpha on nitrite accumulation. In
      accordance with these findings, IL-1beta- and TNF-alpha-induced a time-dependent
      increase in Erk1/Erk2 activation. This cytokine action was completely abolished
      by PD098,059 but was not altered by PDTC. Finally, IL-1beta and TNF-alpha induced
      degradation of NF-kappaB's bound inhibitory protein, IkappaB-alpha, leading to
      translocation of NF-kappaB into the nucleus. IkappaB-alpha expression was not
      restored to control levels by inhibition of MEK. Furthermore, inhibition of MEK
      with PD098,059 did not alter IL-1beta- and TNF-alpha-induced expression of active
      NF-kappaB. The results demonstrate that autonomous Erk and NF-kappaB pathways
      mediate cytokine-induced increases in iNOS expression in astroglia.

PMID- 12509806
TI  - Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with
      lypopolysaccharide.
AB  - Upon activation, brain microglial cells release proinflammatory mediators, such
      as TNFalpha, which may play an important role in eliciting neuroinflammatory
      processes causing brain damage. As cannabinoids have been reported to exert anti
      inflammatory and neuroprotective actions in the brain, we here examined the
      effect of both synthetic and endogenous cannabinoids on TNFalpha release elicited
      by bacterial endotoxin lypopolysaccharide (LPS) in cultured microglia. Exposure
      of primary cultures of rat cortical microglial cells to LPS significantly
      stimulated TNFalpha mRNA expression and release. The endogenous cannabinoids
      anandamide and 2-arachidonylglycerol (2-AG), as well as the synthetic
      cannabinoids (+)WIN 55,212-2, CP 55,940, and HU210, inhibited in a concentration
      dependent manner (1-10 microM) the LPS-induced TNFalpha release. Unlike the high
      affinity cannabinoid receptor agonist (+)WIN 55,212-2, the low-affinity
      stereoisomer (-)WIN 55,212-2 did not exert any significant inhibition on TNFalpha
      release. Given this stereoselectivity, the ability of (+)WIN 55,212-2 to inhibit
      LPS-induced TNFalpha release from microglia is most likely receptor-mediated. By
      RT-PCR we found that the two G(i/o) protein-coupled cannabinoid receptors (type 1
      and 2) are both expressed in microglial cultures. However, selective antagonists
      of type 1 (SR141716A and AM251) and type 2 (SR144528) cannabinoid receptors did
      not affect the effect of (+)WIN 55,212-2. Consistent with this finding is the
      observation that the ablative effect of (+)WIN 55,212-2 on LPS-evoked release of
      TNFalpha was not sensitive to the G(i/o) protein inactivator pertussis toxin. In
      addition, the cAMP elevating agents dibutyryl cAMP and forskolin both abolished
      LPS-induced TNFalpha release, thus rendering unlikely the possibility that (+)WIN
      55,212-2 could ablate TNFalpha release through the inhibition of adenylate
      cyclase via the G(i)-coupled cannabinoid receptors type 1 and 2. In summary, our
      data indicate that both synthetic and endogenous cannabinoids inhibit LPS-induced
      release of TNFalpha from microglial cells. By showing that such effect does not
      appear to be mediated by either CB receptor type 1 or 2, we provide evidence
      suggestive of the existence of yet unidentified cannabinoid receptor(s) in brain
      microglia.

PMID- 12509807
TI  - Astrocytic expression of the Alzheimer's disease beta-secretase (BACE1) is
      stimulus-dependent.
AB  - The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of
      beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta
      amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is
      neuronally expressed in the brains of humans and experimental animals such as
      mice and rats. In addition, we have recently shown that BACE1 protein is
      expressed by reactive astrocytes in close proximity to beta-amyloid plaques in
      the brains of aged transgenic Tg2576 mice that overexpress human amyloid
      precursor protein carrying the double mutation K670N-M671L. To address the
      question whether astrocytic BACE1 expression is an event specifically triggered
      by beta-amyloid plaques or whether glial cell activation by other mechanisms also
      induces BACE1 expression, we used six different experimental strategies to
      activate brain glial cells acutely or chronically. Brain sections were processed
      for the expression of BACE1 and glial markers by double immunofluorescence
      labeling and evaluated by confocal laser scanning microscopy. There was no
      detectable expression of BACE1 protein by activated microglial cells of the
      ameboid or ramified phenotype in any of the lesion paradigms studied. In
      contrast, BACE1 expression by reactive astrocytes was evident in chronic but not
      in acute models of gliosis. Additionally, we observed BACE1-immunoreactive
      astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice
      and Alzheimer's disease patients.

PMID- 12509808
TI  - Endothelin B receptors are expressed by astrocytes and regulate astrocyte
      hypertrophy in the normal and injured CNS.
AB  - The ability of mammalian central nervous system (CNS) neurons to survive and/or
      regenerate following injury is influenced by surrounding glial cells. To identify
      the factors that control glial cell function following CNS injury, we have
      focused on the endothelin B receptor (ET(B)R), which we show is expressed by the
      majority of astrocytes that are immunoreactive for glial acid fibrillary protein
      (GFAP) in both the normal and crushed rabbit optic nerve. Optic nerve crush
      induces a marked increase in ET(B)R and GFAP immunoreactivity (IR) without
      inducing a significant increase in the number of GFAP-IR astrocytes, suggesting
      that the crush-induced astrogliosis is due primarily to astrocyte hypertrophy. To
      define the role that endothelins play in driving this astrogliosis, artificial
      cerebrospinal fluid (CSF), ET-1 (an ET(A)R and ET(B)R agonist), or Bosentan (a
      mixed ET(A)R and ET(B)R antagonist) were infused via osmotic minipumps into
      noninjured and crushed optic nerves for 14 days. Infusion of ET-1 induced a
      hypertrophy of ET(B)R/GFAP-IR astrocytes in the normal optic nerve, with no
      additional hypertrophy in the crushed nerve, whereas infusion of Bosentan induced
      a significant decrease in the hypertrophy of ET(B)R/GFAP-IR astrocytes in the
      crushed but not in the normal optic nerve. These data suggest that
      pharmacological blockade of astrocyte ET(B)R receptors following CNS injury
      modulates glial scar formation and may provide a more permissive substrate for
      neuronal survival and regeneration.

PMID- 12509809
TI  - Suppression of activated microglia promotes survival and function of transplanted
      oligodendroglial progenitors.
AB  - To evaluate the functional consequence of microglial activation in vivo,
      oligodendroglial progenitors were transplanted into the spinal cord of Long Evans
      shaker, a myelin mutant rat in which myelin defects are associated with
      progressive microglial activation. Cells grafted into neonatal rats at the
      initiation of gliosis successfully myelinated axons. However, cells transplanted
      during peak microglial activation did not lead to myelination due to death of the
      grafted cells within 3 days after transplantation. Pretreatment of these animals
      with minocycline, a tetracycline derivative, resulted in cell survival and
      myelination by the grafted cells. In culture, minocycline did not affect the
      survival, proliferation, or differentiation of oligodendroglial progenitors.
      Hence, minocycline likely modulates the function of reactive glia in vivo to
      promote the survival and myelination of transplanted oligodendroglial
      progenitors.

PMID- 12509810
TI  - Sphingosine 1-phosphate induces the production of glial cell line-derived
      neurotrophic factor and cellular proliferation in astrocytes.
AB  - Sphingosine 1-phosphate (S1P) is a platelet-derived bioactive sphingolipid that
      evokes a variety of biological responses. To understand the role of S1P in the
      central nervous system, we have examined the effect of S1P on the production of
      glial cell line-derived neurotrophic factor (GDNF) and growth regulation of
      cortical astrocytes from rat embryo. Moreover, we examined the possibility that
      the expression of GDNF is regulated differently in cultured astrocytes from the
      stroke-prone spontaneously hypertensive rat (SHRSP) than in those from Wistar
      kyoto rats (WKY). The mRNA expression was quantitated by RT-PCR based on the
      fluorescent TaqMan methodology. A new instrument capable of measuring
      fluorescence in real time was used to quantify gene amplification in astrocytes.
      GDNF protein was investigated by enzyme-linked immunosorbent assay. S1P induced
      the expression of GDNF mRNA and the production of GDNF protein in a dose
      dependent manner in WKY astrocytes. Moreover, S1P increased cell numbers and
      induced the proliferation of astrocytes. In addition, the level of mRNA
      expression and protein production of GDNF was significantly lower in SHRSP than
      WKY astrocytes following exposure to S1P. These findings revealed that S1P
      augments GDNF protein production and cellular growth in astrocytes. Also, our
      results indicate that production in SHRSP astrocytes was attenuated in response
      to S1P compared with that observed in WKY. We conclude that S1P specifically
      triggers a cascade of events that regulate the production of GDNF and cell growth
      in astrocytes. Our results also suggest that the reduced expression of GDNF
      caused by S1P is a factor in the stroke proneness of SHRSP.

PMID- 12509811
TI  - Alzheimer's disease is associated with a selective increase in alpha7 nicotinic
      acetylcholine receptor immunoreactivity in astrocytes.
AB  - Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common forms of
      dementia in the elderly associated with cholinergic dysfunction, including
      reductions in nicotinic acetylcholine receptors (nAChRs). In AD, astrocytes are
      implicated in the formation of senile plaques, one of the core pathological
      features. Using immunohistochemistry, we have investigated astrocytic expression
      of the two major nicotinic receptor alpha subunits in the human hippocampus and
      entorhinal cortex. alpha7, but not alpha4, subunit immunoreactivity was
      associated with astrocytes. An increase in the proportion of astrocytes
      expressing alpha7 immunoreactivity was observed in AD compared with age-matched
      controls. A similar increase was not evident in DLB. Elevated alpha7 nAChRs on
      astrocytes in AD may contribute to alterations in calcium homeostasis and nitric
      oxide production, which in turn could affect beta-amyloid-mediated inflammatory
      processes in AD.

PMID- 12509813
TI  - High-resolution assessment of blood flow in murine RIF-1 tumors by monitoring
      uptake of H(2)(17)O with proton T(1rho)-weighted imaging.
AB  - Perfusion parameters, such as blood flow, are critical properties of tumors
      related to angiogenesis, drug delivery, radiosensitivity, bioenergetic status,
      and steady state levels of metabolites, such as lactate, that have been proposed
      as indices of tumor response to therapy. The existing MR methods for measuring
      tumor blood flow (TBF) have limitations related to sensitivity, spatial
      resolution, or dependence on other physiological properties such as vascular
      permeability. To address many of these difficulties, this study introduces the
      use of an (17)O-enriched tracer in conjunction with high-resolution, indirect MRI
      to measure TBF. To demonstrate the advantages of this technique, relative TBF was
      measured in subcutaneous RIF-1 tumors in C3H mice by monitoring the uptake of
      H(2) (17)O with a resolution of 0.16 x 0.31 x 3 mm in 13 sec. At this resolution,
      tumor heterogeneity with respect to blood flow is clearly visible. Measurement of
      the tracer arterial input function, which is necessary for determination of
      absolute blood flow, may be facilitated with improved temporal resolution.

PMID- 12509814
TI  - Determining and visualizing uncertainty in estimates of fiber orientation from
      diffusion tensor MRI.
AB  - Diffusion tensor MRI (DT-MRI) permits determination of the dominant orientation
      of structured tissue within an image voxel. This has led to the development of 2D
      graphical methods for representing fiber orientation and DT-MRI "tractography,"
      which aims to reconstruct the 3D trajectories of white matter fasciculi. Most
      contemporary fiber orientation mapping schemes and tractography algorithms employ
      the directional information contained in the eigenvectors of the diffusion tensor
      to approximate white matter fiber orientation. However, while the uncertainty
      associated with every estimate of an eigenvector has long been recognized, no
      attempts to quantify this uncertainty in vivo have been reported. Here, a method
      is proposed for determining confidence intervals in fiber orientation from real
      DT-MRI data using the bootstrap method. This is used to construct maps of the
      "cone of uncertainty," allowing simultaneous viewing of fiber orientation and its
      uncertainty, and to examine the relationship between orientation uncertainty and
      tissue anisotropy.

PMID- 12509815
TI  - Co-registration of acquired MR ventilation and perfusion images--validation in a
      porcine model.
AB  - Under controlled imaging conditions, functional, co-registered ventilation and
      perfusion images were obtained for quantitative MRI assessment of pulmonary
      function. Experiments were conducted on 25-35 kg Yorkshire pigs (N = 5) under
      ketamine/isoflurane anesthesia. Ventilation and perfusion MR images were obtained
      using laser polarized gas and gadolinium (Gd), respectively. The mutual
      information-based technique was used to quantify the initial misregistration
      between the acquired ventilation and perfusion images, to cope with different
      intensity characteristics. Means and standard deviations (SDs) of
      misregistrations for the five subjects, in terms of absolute translation and
      absolute rotations around each of the three coordinate axes, were computed to
      evaluate the hypothesis. For qualitative illustrations, plots of mutual
      information values under absolute translations and rotations around each of the
      three coordinate axes are presented. This preliminary study shows the feasibility
      of acquiring functional image data that are spatially co-registered. This method
      has potential applications in the quantitative assessment of regional alveolar
      ventilation and pulmonary perfusion ratio, in both normal and diseased lung.

PMID- 12509816
TI  - Parameterized evaluation of macromolecules and lipids in proton MR spectroscopy
      of brain diseases.
AB  - Short echo time (TE) proton MR spectra of the brain include signals of several
      metabolites as well as macromolecules. In various pathologies, such as brain
      tumors and multiple sclerosis (MS), the presence of mobile lipids or
      pathologically altered macromolecules may provide useful additional diagnostic
      information. A reliable quantitation of these resonances, however, is often not
      possible due to the lack of adequate prior knowledge. Furthermore, even if
      advanced fitting procedures are used, a reliable evaluation of metabolites in the
      presence of pathological lipids or macromolecules often fails if the latter are
      omitted in the spectral evaluation. In this study, a method is presented for the
      simultaneous evaluation of all visible components, including metabolites, lipids,
      and macromolecules, by the use of the fitting procedure LCModel. A standard basis
      set of brain metabolites was extended by inclusion of parameterized components
      for macromolecules and lipids that were derived from metabolite-nulled in vivo
      spectra of normal brain and high-grade gliomas, respectively. The improved
      spectral quantitation is demonstrated in glial brain tumors and MS lesions as
      well as in normal brain. It is pointed out that both macromolecules and lipids
      must be included to provide a proper spectral evaluation.

PMID- 12509817
TI  - Automated classification of short echo time in in vivo 1H brain tumor spectra: a
      multicenter study.
AB  - Automated pattern recognition techniques are needed to help radiologists
      categorize MRS data of brain tumors according to histological type and grade. A
      major question is whether a computer program "trained" on spectra from one
      hospital will be able to classify those from another, particularly if the
      acquisition protocol is different. A subset of 144 histopathologically validated
      brain tumor spectra in the INTERPRET database, obtained from three of the
      collaborating centers, was grouped into meningiomas, low-grade astrocytomas, and
      "aggressive tumors" (glioblastomas and metastases). Spectra from two centers
      formed the training set (94 spectra) while the third acted as the test set (50
      spectra). Linear discriminant analysis successfully classified 48/50 in the test
      set; the remaining two were atypical cases. When the training and test sets were
      combined, 133 of the 144 spectra were correctly classified using the leave-one
      out procedure. These spectra had been obtained using different sequences (STEAM
      and PRESS), different echo times (20, 30, 31, and 32 ms), different repetition
      times (1600 and 2000 ms), and different manufacturers' instruments (GE and
      Philips). Pattern recognition algorithms are less sensitive to acquisition
      parameters than had been expected.

PMID- 12509818
TI  - Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR
      spectroscopy.
AB  - Localized, water-suppressed (1)H-[(13)C]-NMR spectroscopy was used to detect
      (13)C-label accumulation in cerebral metabolites following the intravenous
      infusion of [1,6-(13)C(2)]-glucose (Glc). The (1)H-[(13)C]-NMR method, based on
      adiabatic RF pulses, 3D image-selected in vivo spectroscopy (ISIS) localization,
      and optimal shimming, yielded high-quality (1)H-[(13)C]-NMR spectra with optimal
      NMR sensitivity. As a result, the (13)C labeling of [4-(13)C]-glutamate (Glu) and
      [4-(13)C]-glutamine (Gln) could be detected from relatively small volumes (100
      microL) with a high temporal resolution. The formation of [n-(13)C]-Glu, [n
      (13)C]-Gln (n = 2 or 3), [2-(13)C]-aspartate (Asp), [3-(13)C]-Asp, [3-(13)C]
      alanine (Ala), and [3-(13)C]-lactate (Lac) was also observed to be reproducible.
      The (13)C-label incorporation curves of [4-(13)C]-Glu and [4-(13)C]-Gln provided
      direct information on metabolic pathways. Using a two-compartment metabolic
      model, the tricarboxylic acid (TCA) cycle flux was determined as 0.52 +/- 0.04
      micromol/min/g, while the glutamatergic neurotransmitter flux equaled 0.25 +/-
      0.05 micromol/min/g, in good correspondence with previously determined values.

PMID- 12509819
TI  - Comparison of the dependence of blood R2 and R2* on oxygen saturation at 1.5 and
      4.7 Tesla.
AB  - Gradient-echo (GRE) blood oxygen level-dependent (BOLD) effects have both intra-
      and extravascular contributions. To better understand the intravascular
      contribution in quantitative terms, the spin-echo (SE) and GRE transverse
      relaxation rates, R(2) and R(2)(*), of isolated blood were measured as a function
      of oxygenation in a perfusion system. Over the normal oxygenation saturation
      range of blood between veins, capillaries, and arteries, the difference between
      these rates, R'(2) = R(2)(*) - R(2), ranged from 1.5 to 2.1 Hz at 1.5 T and from
      26 to 36 Hz at 4.7 T. The blood data were used to calculate the expected
      intravascular BOLD effects for physiological oxygenation changes that are typical
      during visual activation. This modeling showed that intravascular DeltaR(2)(*) is
      caused mainly by R(2) relaxation changes, namely 85% and 78% at 1.5T and 4.7T,
      respectively. The simulations also show that at longer TEs (>70 ms), the
      intravascular contribution to the percentual BOLD change is smaller at high field
      than at low field, especially for GRE experiments. At shorter TE values, the
      opposite is the case. For pure parenchyma, the intravascular BOLD signal changes
      originate predominantly from venules for all TEs at low field and for short TEs
      at high field. At longer TEs at high field, the capillary contribution dominates.
      The possible influence of partial volume contributions with large vessels was
      also simulated, showing large (two- to threefold) increases in the total
      intravascular BOLD effect for both GRE and SE.

PMID- 12509820
TI  - Investigating the BOLD effect during infusion of Gd-DTPA using rapid T2* mapping.
AB  - This work aimed to investigate the effects of administering Gd-DTPA on the BOLD
      effect, and to determine the feasibility of using this approach to measure
      fractional changes in blood volume and blood oxygenation on neuronal activation
      during a visual paradigm. A linear relationship between cortical R(2)(*) and the
      intravascular concentration of Gd-DTPA was demonstrated. The change in R(2)(*) in
      the visual cortex on activation at 3 T (in the absence of Gd-DTPA) was found to
      be 1.38 +/- 0.31 s(-1) (N = 4). The fractional change in total blood volume
      during visual activation was calculated to be 28% +/- 7% (N = 4). The absolute
      increase in venous blood oxygenation on activation (DeltaY) was estimated to be
      21% +/- 4% (N = 4) (assuming HCT = 0.4, resting blood oxygenation = 60%, fraction
      of volume change that was venous = 36%, and the resting venous fraction of the
      blood volume = 70%). Simulations showed that the estimated change in venous blood
      oxygenation was sensitive to the assumed venous blood fraction, and that the
      estimated fractional change in blood oxygenation was insensitive to whether the
      change in blood volume occurred in the arterial or venous network.

PMID- 12509821
TI  - Comparison of quantitative shear wave MR-elastography with mechanical compression
      tests.
AB  - The mechanical properties of in vivo soft tissue are generally determined by
      palpation, ultrasound measurements (US), and magnetic resonance elastography
      (MRE). While it has been shown that US and MRE are capable of quantitatively
      measuring soft tissue elasticity, there is still some uncertainty about the
      reliability of quantitative MRE measurements. For this reason it was decided to
      determine in vitro how MRE measurements correspond with other quantitative
      methods of measuring characteristic elasticity values. This article presents the
      results of experiments with tissue-like agar-agar gel phantoms in which the
      wavelength of strain waves was measured by shear wave MR elastography and the
      resultant shear modulus was compared with results from mechanical compression
      tests with small gel specimens. The shear moduli of nine homogeneous gels with
      various agar-agar concentrations were investigated. The elasticity range of the
      gels covered the elasticity range of typical soft tissues. The systematic
      comparison between shear wave MRE and compression tests showed good agreement
      between the two measurement techniques.

PMID- 12509822
TI  - Measurement of regional lung function in rats using hyperpolarized 3helium
      dynamic MRI.
AB  - Dynamic regional lung function was investigated in rats using a radial
      acquisition cine (RA-CINE) pulse sequence together with hyperpolarized (HP) (3)He
      gas delivered by a constant flow ventilator. Based on regional differences in the
      behavior of inspired air, the lung was conceptually divided into two regions (the
      major airways and the peripheral airspace) for purposes of functional analysis.
      To measure regional function in the major airways, a large RF flip angle (24
      degrees) was applied to reduce (3)He magnetization in the peripheral airspace,
      and signal intensity (SI) was normalized with the projected airway diameter to
      estimate local airflow. Higher normalized signal intensity was observed in the
      left branch airway as compared to the right branch airway. To determine regional
      function in the peripheral airspace, a small RF flip angle (6 degrees) was used.
      Incremental increases of peripheral SI in successive lung images were consistent
      with the increase in lung volume. A new "skipping" scanning strategy using dummy
      frames allows a trade-off between the number of frames acquired for dynamic
      information, the RF flip angle, and the penetration depth of (3)He magnetization
      into the lung. This work provides a novel approach to simultaneously assess
      dynamic regional function and morphology.

PMID- 12509823
TI  - Feasibility of MR-guided focused ultrasound with real-time temperature mapping
      and continuous sonication for ablation of VX2 carcinoma in rabbit thigh.
AB  - The efficiency of MRI-guided focused ultrasound (FUS) hyperthermia with
      continuous sonication was investigated for the treatment of VX2 carcinoma
      implanted in rabbit thigh muscle. Six rabbits were treated with a single session
      of FUS when the tumor diameter exceeded 2 cm (10-21 days after implant). The FUS
      treatment method was based on a spiral trajectory of the focal point that allows
      continuous sonication under automatic, real-time MR guidance. The total heating
      time was approximately 1000 sec. Efficacy of treatment was evaluated twice a week
      based on clinical (weight) and MRI data. Treated animals were sacrificed 5 weeks
      after the heating procedure and histological analysis was performed. Tumor
      regression was observed in each treated animal. Complete ablation of tumor, with
      confirmation by histological analysis, was obtained in five of six treated cases.
      Tumor regrowth occurred in one animal. Thermal injury was limited to the targeted
      region in three cases, but ablation also reached some healthy muscle around the
      tumor in the other three cases. A good correlation was found between postmortem
      histological analysis and premortem MRI data. Efficacy of MR-controlled
      hyperthermia using FUS heating with spiral trajectories was demonstrated for
      successful local control of intramuscular VX2 tumor.

PMID- 12509824
TI  - Imaging of ischemia and infarction in blood-perfused pig hearts using 87Rb MRI.
AB  - 87Rb-MRI was used to measure Rb(+) uptake in blood-perfused pig hearts during
      complete occlusion (120 and 70 min) of the left anterior descending artery (LAD)
      and subsequent reperfusion (120 and 170 min). The Rb(+) uptake rate and maximal
      Rb image intensity during 120-min occlusion were significantly lower in the
      ischemic anterior left ventricular (LV) wall (0.35 +/- 0.14%/min and 26 +/- 4.7%)
      relative to those in the remote posterior LV wall (2.43 +/- 0.33%/min and 98 +/-
      10%). Reperfusion after 120 and 70 min of occlusion resulted in formation of
      damaged areas, which had 40 +/- 4 and 73 +/- 10% of the (87)Rb image intensity
      observed in the remote posterior wall. The infarct sizes determined
      histologically by triphenyltetrazolium chloride staining were 9.6 +/- 3.4 and 5.6
      +/- 4.6% of the total ventricular mass (LV + RV) in the 120- and 70-min occlusion
      groups, respectively. The sizes determined by MRI were 13.1 +/- 2 and 2.8 +/-
      4.3% of the total number of pixels, respectively. The Rb(+) uptake in the
      anterior wall during 120-min occlusion was somewhat lower than that previously
      observed in crystalloid-perfused hearts. It is concluded that blood does not
      interfere with the ability of (87)Rb MRI to detect ischemic and infarct areas.

PMID- 12509825
TI  - Correlation between BOLD-fMRI and EEG signal changes in response to visual
      stimulus frequency in humans.
AB  - The correlation between signals acquired using electroencephalography (EEG) and
      fMRI was investigated in humans during visual stimulation. Evoked potential EEG
      and BOLD fMRI data were acquired independently under similar conditions from
      eight subjects during stimulation by a checkerboard flashed at frequencies
      ranging from 2-12 Hz. The results indicate highly correlated changes in the
      strength of the EEG signal averaged over two occipital electrodes and the BOLD
      signal within the occipital lobe as a function of flash frequency for 7/8
      subjects (average linear correlation coefficient of 0.76). Both signals peaked at
      approximately 8 Hz. For one subject the correlation coefficient was 0.20; the EEG
      signal peaked at 6 Hz and the BOLD signal peaked at 10 Hz. Overall, the EEG and
      BOLD signals, each averaged over 40-sec stimulation periods, appear to be coupled
      linearly during visual stimulation by a flashing checkerboard.

PMID- 12509826
TI  - Performance of a new gadolinium-based intravascular contrast agent in free
      breathing inversion-recovery 3D coronary MRA.
AB  - In three-dimensional (3D) coronary magnetic resonance angiography (MRA), the in
      flow contrast between the coronary blood and the surrounding myocardium is
      attenuated as compared to thin-slab two-dimensional (2D) techniques. The
      application of a gadolinium (Gd)-based intravascular contrast agent may provide
      an additional source of signal and contrast by reducing T(1blood) and supporting
      the visualization of more distal or branching segments of the coronary arterial
      tree. In six healthy adults, the left coronary artery (LCA) system was imaged pre
      and postcontrast with a 0.075-mmol/kg bodyweight dose of the intravascular
      contrast agent B-22956. For imaging, an optimized free-breathing, navigator-gated
      and -corrected 3D inversion recovery (IR) sequence was used. For comparison,
      state-of-the-art baseline 3D coronary MRA with T(2) preparation for non-exogenous
      contrast enhancement was acquired. The combination of IR 3D coronary MRA,
      sophisticated navigator technology, and B-22956 allowed for an extensive
      visualization of the LCA system. Postcontrast, a significant increase in both the
      signal-to-noise ratio (SNR; 46%, P < 0.05) and contrast-to-noise ratio (CNR;
      160%, P < 0.01) was observed, while vessel sharpness of the left anterior
      descending (LAD) artery and the left coronary circumflex (LCX) were improved by
      20% (P < 0.05) and 18% (P < 0.05), respectively.

PMID- 12509827
TI  - Signal-to-noise ratio effects in quantitative cerebral perfusion using dynamic
      susceptibility contrast agents.
AB  - Theoretical and simulation evidence is presented in support of the idea that the
      optimal manner of determining blood flow from MR perfusion studies is not
      necessarily obtained by setting experimental conditions to maximize either the
      arterial input or the measured tissue concentration level for a particular echo
      time (TE). The noise power in the contrast concentration curve is associated with
      its peak because of the nonlinear relationship between the contrast concentration
      and MR signal intensity curves. The optimum signal-to-noise ratio (SNR), SNR(C),
      for a particular contrast concentration curve can be obtained when the
      experimental concentration level and TE are adjusted to produce an MR intensity
      curve whose signal loss is 63% of the precontrast MR signal intensity. It is
      demonstrated that the stability of the singular valued decomposition (SVD)
      deconvolution approach to determine blood flow parameters is increased when the
      tissue curve maximum signal loss is in the range of 40-80%. The accuracy and
      stability of the SVD-determined blood flow parameters are affected by deviations
      from these optimum conditions in a manner that depends on the mean transit time
      (MTT) associated with the residue function. It is recommended that the
      experimental TE value be set so that neither the tissue nor the arterial curves
      are placed a region of rapidly deteriorating SNR(C).

PMID- 12509828
TI  - Interventional MRA using actively visualized catheters, TrueFISP, and real-time
      image fusion.
AB  - An integrated system for performing interventional magnetic resonance angiography
      (MRA) with actively visualized instruments and real-time image fusion was
      implemented on a 1.5 T scanner. True fast imaging with steady precession
      (TrueFISP) imaging provided high acquisition speed paired with high signal-to
      noise ratio (SNR) and contrast-to-noise ratio (CNR) for the simultaneous
      visualization of active instruments and arterial morphology. The system enabled
      simultaneous image reconstruction and image postprocessing of multiple receiver
      channels, with subsequent image fusion display in real time. Optional interleaved
      image acquisition in two planes provided additional important information for
      biplanar instrument guidance. Various vascular interventions, including selective
      catheterization and subsequent selective MRA of the abdominal aorta, renal
      arteries, superior mesenteric artery (SMA), hepatic artery, and aortic arch, were
      performed on 10 pigs under MR guidance. In terms of instrument contrast, image
      acquisition, reconstruction, and fusion speed, the setup represents a powerful
      platform for performing interventional MRA procedures.

PMID- 12509829
TI  - Motion correction in MRI using an apparatus for dynamic angular position tracking
      (ADAPT).
AB  - Motion during MRI examinations is a serious problem that degrades the quality of
      the data (images) acquired. Motion can be corrected during the postprocessing of
      the data; however, this approach is suboptimal and is typically limited to in
      plane or translational motion. An apparatus for dynamic angular position tracking
      (ADAPT) for prospective angular motion correction has been developed. This
      application is capable of "tracking" the scanned region of interest by performing
      dynamic adjustments of orientation of the scanning plane. The operation of the
      apparatus is based on deuterium MR spectroscopy and does not rely on the use of
      magnetic field gradients. Orientation-sensitive deuterium quadrupolar interaction
      in a single crystal attached to a subject is used to monitor the angular position
      in magnetic fields. Measurements are performed with an independent spectrometer
      channel in the background of the MRI scans. This apparatus is very cost- and time
      efficient because it utilizes the hardware already available on many
      spectrometers and can be used in parallel with MRI scans. Potentially, rotations
      by a fraction of one degree can be easily corrected and the angular position
      information can be rapidly updated.

PMID- 12509830
TI  - Transmit SENSE.
AB  - The idea of using parallel imaging to shorten the acquisition time by the
      simultaneous use of multiple receive coils can be adapted for the parallel
      transmission of a spatially-selective multidimensional RF pulse. As in data
      acquisition, a multidimensional RF pulse follows a certain k-space trajectory.
      Shortening this trajectory shortens the pulse duration. The use of multiple
      transmit coils, each with its own time-dependent waveform and spatial
      sensitivity, can compensate for the missing parts of the excitation k-space. This
      results in a maintained spatial definition of the pulse profile, while its
      duration is reduced. This work introduces the concept of parallel transmission
      with arbitrarily shaped transmit coils (termed "Transmit SENSE"). Results of
      numerical studies demonstrate the theoretical feasibility of the approach. The
      experimental proof of principle is provided on a commercial MR scanner. The lack
      of multiple independent transmit channels was addressed by combining the
      excitation patterns from two separate subexperiments with different transmit
      setups. Shortening multidimensional RF pulses could be an interesting means of
      making 3D RF pulses feasible even for fast T(2)(*) relaxing species or strong
      main field inhomogeneities. Other applications might benefit from the ability of
      Transmit SENSE to improve the spatial resolution of the pulse profile while
      maintaining the transmit duration.

PMID- 12509831
TI  - Reduction of transient signal oscillations in true-FISP using a linear flip angle
      series magnetization preparation.
AB  - An electrocardiogram (ECG)-triggered, magnetization-prepared, segmented, 3D true
      fast imaging with steady-state precession (true-FISP) sequence with fat
      saturation was recently proposed for coronary artery imaging. A magnetization
      preparation scheme consisting of an alpha/2 radiofrequency (RF) pulse followed by
      20 constant flip angle dummy RF cycles was used to reduce signal oscillations in
      the approach to steady state. However, if large resonance offsets on the order of
      70-100 Hz are present, significant magnetization oscillations will still occur
      during data acquisition, which will result in image ghosting and blurring. The
      goal of this work was to validate that a linear flip angle (LFA) series can be
      used during magnetization preparation to reduce these image artifacts. Computer
      simulations, phantom studies, and coronary artery imaging in healthy volunteers
      were performed to compare this magnetization preparation scheme with that of an
      alpha/2 pulse followed by constant flip angle dummy RF cycles. The results
      demonstrated substantial reduction in the apparent image artifacts when using
      linearly increasing flip angles during magnetization preparation.

PMID- 12509832
TI  - Multiple-mouse MRI.
AB  - Several theoretical parallel-imaging approaches are evaluated that seek to
      improve the efficiency of an MRI experiment involving multiple small samples,
      such as mice. The best method for our mouse phenotyping application is chosen in
      terms of efficiency and ease of implementation, and the approach is demonstrated
      at 1.5 T on a clinical scanner with an array of four shielded birdcage coils with
      four parallel receivers. Electronic interactions between the receiver channels in
      the system are quantified and a novel sensitivity-encoding (SENSE)-like
      postprocessing method is described to remove the resulting image ghosts. In
      parallel imaging with a four-coil array, the time required for three-dimensional
      (3D) high-resolution imaging of four mice is reduced to one-fourth the time that
      it would take to image the mice sequentially.

PMID- 12509833
TI  - Does binding of Gd-DTPA to myocardial tissue contribute to late enhancement in a
      model of acute myocardial infarction?
AB  - The long-lasting signal enhancement by Gd-DTPA in areas of myocardial infarction
      has been conventionally explained by low perfusion and an enhanced Gd
      distribution volume. To test whether binding of Gd to myocardial constituents is
      an additional factor contributing to this effect, Gd-DTPA was allowed to
      equilibrate between homogenized porcine myocardial tissue and physiological
      saline. The relaxation rate (1/T(1)) of homogenate samples (n = 61) increased in
      proportion (r(2) = 0.98) to the Gd concentration (0.025-0.5 mM) of the
      surrounding medium, with no evidence for augmented uptake. The diffusion-limited
      uptake was only slightly more rapid than the subsequent Gd-release. The amount of
      Gd released was in line with all of the Gd-DTPA in the homogenate participating
      in water proton relaxation. The data from this acute myocardial infarction model
      do not support the notion that Gd-DTPA binding in the early stages of myocardial
      damage contributes to delayed enhancement.

PMID- 12509834
TI  - On- and off-resonance T(1rho) MRI in acute cerebral ischemia of the rat.
AB  - The ability of on-resonance T(1rho) (T(1rho)) and off-resonance T(1rho)
      (T(1rho)(off)) measurements to indicate acute cerebral ischemia in a rat model of
      transient middle cerebral artery (MCA) occlusion was investigated at 4.7 T.
      T(1rho) was determined with B(1) fields of 0.4, 0.8, and 1.6 G, and T(1rho)(off)
      with five offset frequencies ((Delta)omega) ranging from 0-7.5 kHz at B(1) of 0.4
      G, yielding effective B(1) (B(eff)) from 0.4 to 1.8 G. Diffusion, T(1), and T(2)
      were also quantified. Both T(1rho) and T(1rho)(off) acquired with (Delta)(o)< 2.5
      kHz showed positive contrast during the first hours of MCA occlusion in the
      ischemic tissue delineated by low diffusion. Interestingly, T(1rho)(off) contrast
      acquired with (Delta)omega > 2.5 kHz was clearly less sensitive to ischemic
      alterations, and developed with a delayed time course. This discrepancy is
      thought to be a consequence of the frequency dependency of cross-relaxation
      during irradiation with spin-lock pulses.

PMID- 12509835
TI  - Reduction of eddy-current-induced distortion in diffusion MRI using a twice
      refocused spin echo.
AB  - Image distortion due to field gradient eddy currents can create image artifacts
      in diffusion-weighted MR images. These images, acquired by measuring the
      attenuation of NMR signal due to directionally dependent diffusion, have recently
      been shown to be useful in the diagnosis and assessment of acute stroke and in
      mapping of tissue structure. This work presents an improvement on the spin-echo
      (SE) diffusion sequence that displays less distortion and consequently improves
      image quality. Adding a second refocusing pulse provides better image quality
      with less distortion at no cost in scanning efficiency or effectiveness, and
      allows more flexible diffusion gradient timing. By adjusting the timing of the
      diffusion gradients, eddy currents with a single exponential decay constant can
      be nulled, and eddy currents with similar decay constants can be greatly reduced.
      This new sequence is demonstrated in phantom measurements and in diffusion
      anisotropy images of normal human brain.

PMID- 12509836
TI  - Reconstruction after rotational motion.
AB  - Patient rotational motion during a scan causes the k-space sampling to be both
      irregular and undersampled. Conventional regridding requires an estimate of the
      sampling density at each measured point and is not strictly consistent with
      sampling theory. Here, a 2D problem is converted to a series of 1D regriddings by
      exact interpolation along the measured readouts. Each 1D regridding, expressed in
      matrix form, requires a matrix inversion to gain an exact solution. Undersampled
      regions make the matrix ill-conditioned but summing the matrix columns (without
      inversion) indicates the undersampled regions. The missing data could be
      reacquired, but in this study it is estimated using a Delaunay triangle-based
      linear interpolation on the original 2D data. The matrix conditioning is
      improved, leading to images with reduced artifacts compared to other regridding
      schemes. Furthermore, there is no requirement to estimate a density compensation
      function at each of the measured points.

PMID- 12509837
TI  - Triggered real-time MRI and cardiac applications.
AB  - Real-time interactive MRI is becoming the method of choice for many cardiac
      applications. One current limitation of real-time techniques is inaccurate slice
      registration during free-breathing. A simple "triggered real-time" imaging
      approach is proposed which enables the acquisition of synchronized and accurately
      registered real-time movie loops during short breathholds. Initial in vivo
      results demonstrate application to complete 4D ventricular function assessment
      and fully resolved flow imaging.

PMID- 12509838
TI  - Fast, automated, N-dimensional phase-unwrapping algorithm.
AB  - This work investigates the general problem of phase unwrapping for arbitrary N
      dimensional phase maps. A cost function-based approach is outlined that leads to
      an integer programming problem. To solve this problem, a best-pair-first region
      merging approach is adopted as the optimization method. The algorithm was
      implemented and tested with 3D MRI medical data for venogram studies, as well as
      for fMRI applications in EPI unwarping and rapid, automated shimming.

PMID- 12509841
TI  - Do calcium channel autoantibodies cause cerebellar ataxia with Lambert-Eaton
      syndrome?

PMID- 12509842
TI  - "Rebooting" the immune system with cyclophosphamide: taking risks for a "cure"?

PMID- 12509843
TI  - New perspectives on developing acute stroke therapy.
AB  - The development of additional acute stroke therapies to complement and supplement
      intravenous recombinant tissue-type plasminogen activator within the first 3
      hours after stroke onset remains an important and pressing need. Much has been
      learned about the presumed target of acute stroke therapy, the ischemic penumbra,
      and clinically available imaging modalities such as magnetic resonance imaging
      and computed tomography hold great promise for at least partially identifying
      this region of potentially salvageable ischemic tissue. Understanding the biology
      of ischemia-related cell injury has also evolved rapidly. New treatment
      approaches to improve outcome after focal brain ischemia will likely be derived
      by looking at naturally occurring adaptive mechanisms such as those related to
      ischemic preconditioning and hibernation. Many clinical trials previously
      performed with a variety of neuroprotective and thrombolytic drugs provide many
      lessons that will help to guide future acute stroke therapy trials and enhance
      the likelihood of success in future trials. Combining knowledge from these three
      areas provides optimism that additional acute stroke therapies can be developed
      to maximize beneficial functional outcome in the greatest proportion of acute
      stroke patients possible.

PMID- 12509844
TI  - Reduction of P/Q-type calcium channels in the postmortem cerebellum of
      paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome.
AB  - The aim of this study was to clarify whether autoimmunity against P/Q-type
      voltage-gated calcium channels (VGCCs) in the cerebellum was associated with the
      pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton
      myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three
      PCD-LEMS patients and six other disease patients including one with LEMS as the
      controls. We compared cerebellar P/Q-type VGCC in these patients and controls for
      the amount and ratio of autoantibody-channel complex using an 125I-omega
      conotoxin MVIIC-binding assay with Scatchard analysis, and their distribution
      using autoradiography. The quantity of cerebellar P/Q-type VGCC measured by
      Scatchard analysis were reduced in PCD-LEMS patients (63.0 +/- 7.0 fmol/mg, n =
      3), compared with the controls (297.8 +/- 38.9 fmol/mg, n = 6). The ratio of
      autoantibody-VGCC complexes to total P/Q-type VGCCs measured by
      immunoprecipitation assay were increased in PCD-LEMS patients. We analysed
      cerebellar specimens by autoradiography using (125)I-omega-conotoxin MVIIC, which
      specifically binds to P/Q-type VGCCs. In PCD-LEMS cerebellum, the toxin binding
      sites of P/Q-type VGCCs were markedly reduced compared with controls, especially
      in the molecular layer, which is the richest area of P/Q-type VGCCs in the normal
      cerebellum. This suggests that P/Q-type VGCCs of the cerebellar molecular layer
      is the immunological target in developing PCD-LEMS.

PMID- 12509845
TI  - Treatment of refractory myasthenia: "rebooting" with high-dose cyclophosphamide.
AB  - Patients with myasthenia gravis (MG) who do not respond to conventional
      immunotherapeutic agents, or cannot tolerate their side effects, are considered
      "refractory." Ablation of the immune system followed by bone marrow transplant
      has been shown to cure experimental MG in rats. It is now known that
      immunoablative treatment with high-dose cyclophosphamide does not damage
      hematopoietic "stem cells," permitting repopulation of the immune system without
      bone marrow transplant. Recent evidence indicates that this treatment can induce
      durable remissions in autoimmune diseases. We treated three myasthenic patients,
      for whom treatment with thymectomy, plasmapheresis, and conventional
      immunotherapeutic agents failed, by using high-dose cyclophosphamide (50mg/kg/day
      intravenously for 4 days) followed by granulocyte colony stimulating factor. All
      three patients tolerated the treatment well and have had marked improvement in
      myasthenic weakness, permitting reduction of immunosuppressive medication to
      minimal levels. Acetylcholine receptor (AChR) antibody levels decreased in two
      AChR antibody-positive patients, and anti-MuSK antibody levels decreased in one
      "AChR antibody-negative" patient. The patients have been followed for up to 3.5
      years, with no recurrence of symptoms. High-dose cyclophosphamide treatment
      appears to be an effective and safe treatment for selected patients with
      refractory MG. Further follow-up of these and additional patients will be needed
      to determine whether the benefit is durable.

PMID- 12509846
TI  - Primary progressive aphasia: PPA and the language network.
AB  - Primary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with
      deterioration of language functions but relative preservation of other cognitive
      domains for at least the first two years of disease. In this study, PPA patients
      with impaired word finding but intact comprehension of conversational speech and
      their matched control subjects were examined using voxel-based morphometry (VBM)
      and functional magnetic resonance imaging (fMRI). fMRI compared signal changes
      during phonological and semantic language tasks with those during a control task
      (matching letters). PPA patients showed longer reaction times and reduced
      accuracy versus controls on the language tasks, but no performance differences on
      the control task. VBM demonstrated reduced gray matter in left superior temporal
      and inferior parietal regions in the PPA group. However, these patients showed a
      normal pattern of activation within the classical language regions. In addition,
      PPA patients showed activations, not seen in normals, in fusiform gyrus,
      precentral gyrus, and intra-parietal sulcus. These activations were found to
      correlate negatively with measures of naming and task performance. The additional
      activations in PPA may therefore represent a compensatory spread of language
      related neural activity or a failure to suppress activity in areas normally
      inhibited during language tasks.

PMID- 12509847
TI  - Environmental enrichment reverses cognitive and molecular deficits induced by
      developmental lead exposure.
AB  - Long-term deficits in cognitive function are the principal effects of lead (Pb2+)
      exposure in children and can be modeled in experimental animals. Current
      therapeutic approaches in the treatment of childhood Pb2+ intoxication are not
      effective in reversing learning deficits once they have occurred. We report that
      environmental enrichment reverses long-term deficits in spatial learning produced
      by developmental Pb2+ exposure in rats. Enhanced learning performance of Pb2+
      exposed animals reared in an enriched environment was associated with recovery of
      deficits in N-methyl-D-aspartate receptor subunit 1 (NR1) mRNA and induction of
      brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of
      environmental enrichment on NR1 and BDNF gene expression was specific to Pb2+
      exposed animals and was present in the absence of changes in the NR2B subunit of
      the N-methyl-D-aspartate receptor, GluR1, alpha CamKII, or PSD-95 gene expression
      measured in the same animals. Our findings demonstrate that the learning
      impairments and NR1 subunit mRNA deficits resulting from developmental Pb2+
      exposure are reversible if the animals are provided with an enriched environment
      even after the exposure has occurred. We propose environmental enrichment as a
      basis for the treatment of childhood Pb2+ intoxication.

PMID- 12509848
TI  - FK506 is neuroprotective in a model of antiretroviral toxic neuropathy.
AB  - Antiretroviral toxic neuropathy is the most common neurological complication of
      human immunodeficiency virus infection. This painful neuropathy not only affects
      the quality of life of human immunodeficiency virus-infected patients but also
      severely limits viral suppression strategies. We have developed an in vitro model
      of this toxic neuropathy to better understand the mechanism of neurotoxicity and
      to test potential neuroprotective compounds. We show that among the
      dideoxynucleosides, ddC appears to be the most neurotoxic, followed by ddI and
      then d4T. This reflects their potency in causing neuropathy. AZT, which does not
      cause a peripheral neuropathy in patients, does not cause significant
      neurotoxicity in our model. Furthermore, in this model, we show that the
      immunophilin ligand FK506 but not cyclosporin A prevents the development of
      neurotoxicity by ddC, as judged by amelioration of ddC-induced "neuritic
      pruning," neuronal mitochondrial depolarization, and neuronal necrotic death.
      This finding suggests a calcineurin-independent mechanism of neuroprotection. As
      calcineurin inhibition underlies the immunosuppressive properties of these
      clinically used immunophilin ligands, this holds promise for the neuroprotective
      efficacy of nonimmunosuppressive analogs of FK506 in the prevention or treatment
      of antiretroviral toxic neuropathy.

PMID- 12509849
TI  - Head cooling with mild systemic hypothermia in anesthetized piglets is
      neuroprotective.
AB  - Hypothermia is potentially therapeutic in the management of neonatal hypoxic
      ischemic brain injury. However, not all studies have shown a neuroprotective
      effect. It is suggested that the stress of unsedated hypothermia may interfere
      with neuroprotection. We propose that selective head cooling (SHC) combined with
      mild total-body hypothermia during anesthesia enhances local neuroprotection
      while minimizing the occurrence of systemic side effects and stress associated
      with unsedated whole-body cooling. Our objective was to determine whether SHC
      combined with mild total-body hypothermia while anesthetized for a period of 24
      hours reduces cerebral damage in our piglet survival model of global hypoxia
      ischemia. Eighteen anesthetized piglets received a 45-minute global hypoxic
      ischemic insult. The pigs were randomized either to remain normothermic or to
      receive SHC. We found that the severity of the hypoxic-ischemic insult was
      similar in the SHC versus the normothermic group, and that the mean neurology
      scores at 30 and 48 hours and neuropathology scores were significantly better in
      the SHC group versus the normothermic group. We conclude that selective head
      cooling combined with mild systemic hypothermia and anesthesia is neuroprotective
      when started immediately after the insult in our piglet model of hypoxic-ischemic
      encephalopathy.

PMID- 12509850
TI  - Human lateral geniculate nucleus and visual cortex respond to screen flicker.
AB  - The first electrophysiological study of the human lateral geniculate nucleus
      (LGN), optic radiation, striate, and extrastriate visual areas is presented in
      the context of presurgical evaluation of three epileptic patients (Patients 1, 2,
      and 3). Visual-evoked potentials to pattern reversal and face presentation were
      recorded with depth intracranial electrodes implanted stereotactically. For
      Patient 1, electrode anatomical registration, structural magnetic resonance
      imaging, and electrophysiological responses confirmed the location of two
      contacts in the geniculate body and one in the optic radiation. The first
      responses peaked approximately 40 milliseconds in the LGN in Patient 1 and 60
      milliseconds in the V1/V2 complex in Patients 2 and 3. Moreover, steady state
      visual-evoked potentials evoked by the unperceived but commonly experienced video
      screen flicker were recorded in the LGN, optic radiation, and V1/V2 visual areas.
      This study provides topographic and temporal propagation characteristics of
      steady state visual-evoked potentials along human visual pathways. We discuss the
      possible relationship between the oscillating signal recorded in subcortical and
      cortical areas and the electroencephalogram abnormalities observed in patients
      suffering from photosensitive epilepsy, particularly video-game epilepsy. The
      consequences of high temporal frequency visual stimuli delivered by ubiquitous
      video screens on epilepsy, headaches, and eyestrain must be considered.

PMID- 12509851
TI  - Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer's
      disease: correlation with cognitive impairment.
AB  - alpha-1-Antichymotrypsin (ACT) is present in neuritic plaques in which it
      participates in the inflammatory cascade of Alzheimer's disease (AD). Reports of
      blood ACT levels in AD, and its usefulness as a disease biomarker, have been
      conflicting. In an effort to clarify this, we measured plasma ACT levels in 516
      white subjects including 359 subjects with probable or possible AD, 44 subjects
      with other late-life dementias, and 113 nondemented people. Subjects with
      systemic inflammatory diseases or who were taking antiinflammatory medications
      were excluded. All patients underwent extensive medical and detailed
      neuropsychological examinations at the time their blood was drawn. We found that
      plasma ACT levels were elevated in AD patients compared with the control group (p
      = 0.01) and were associated with severity of AD dementia; there was a negative
      association with the Mattis Dementia Rating Scale (a global measure of cognition)
      and a positive association with the Clinical Dementia Rating Scale (a global
      functional assessment). These relationships remained significant after
      controlling for demographic and genetic variables. When AD subjects were
      stratified into subgroups by dementia severity, matched by age, education, and
      gender, increased serum ACT correlated with Clinical Dementia Rating Scale (p =
      0.0041) or Mattis Dementia Rating Scale (p = 0.0031) scores. ACT measurements in
      cerebrospinal fluid from an additional 34 AD cases and 16 controls showed
      elevated levels (p = 0.02) in AD. There was a negative correlation (p = 0.037)
      between cerebrospinal fluid ACT levels and clinical severity as measured by the
      Mini-Mental State Examination. Our results demonstrate that peripheral ACT levels
      are elevated in AD, but not in dementias other than AD, and they increase with
      progression of AD dementia. Although not useful as a diagnostic biomarker, ACT
      may reflect disease severity and may be helpful as a within subject biomarker in
      interventions (particularly with antiinflammatory agents) directed at slowing or
      halting progression of disease.

PMID- 12509852
TI  - Correlation between extracellular glucose and seizure susceptibility in adult
      rats.
AB  - In adult diabetic patients, periods of hyperglycemia may be associated with
      exacerbation of focal seizures. Our objective was to determine in the adult rats
      the correlation between seizure susceptibility and extracellular glucose
      concentration in two models of seizures. Male rats were injected with two doses
      of streptozocin (40 mg/kg IP) on 2 consecutive days to induce diabetic
      hyperglycemia. Controls either received vehicle or were not injected. After 2
      weeks, blood glucose concentration was measured, and the rats were subjected to
      flurothyl seizure test. Another group of rats received glucose solution (20%, 5
      ml IP) 30 minutes before testing to induce nondiabetic hyperglycemia. Thresholds
      for flurothyl-induced clonic and tonic-clonic seizures were determined. Finally,
      in vitro epileptiform activity was induced in the entorhinal cortex-hippocampal
      slices from naive rats by perfusing with magnesium-free medium with various
      glucose concentrations. In additional slices, paired-pulse paradigm was
      determined in the perforant path. Susceptibility to clonic and tonic-clonic
      flurothyl-induced seizures positively correlated with blood glucose
      concentrations as the increased glucose concentration was associated with
      proconvulsant effects. Similarly, in the in vitro experiments, epileptiform
      activity was promoted by increased and suppressed by decreased glucose
      concentrations. Data indicate that, in the adult rats, high glucose
      concentrations are associated with proconvulsant effects.

PMID- 12509853
TI  - Motor cortex excitability in Alzheimer's disease: a transcranial magnetic
      stimulation study.
AB  - Motor deficits affect patients with Alzheimer's disease only at later stages.
      Recent studies demonstrate that the primary motor cortex is affected by neuronal
      degeneration accompanied by the formation of amyloid plaques and neurofibrillary
      tangles. It is conceivable that neuronal loss is compensated by reorganization of
      the neural circuitries occurring along the natural course of the disease, thereby
      maintaining motor performances in daily living. Cortical motor output to upper
      limbs was tested via motor-evoked potentials from forearm and hand muscles
      elicited by transcranial magnetic stimulation of motor cortex in 16 patients with
      mild Alzheimer's disease without motor deficits. Motor cortex excitability was
      increased, and the center of gravity of motor cortical output, as represented by
      excitable scalp sites, showed a frontal and medial shift, without correlated
      changes in the site of maximal excitability (hot-spot). This may indicate
      functional reorganization, possibly after the neuronal loss in motor areas.
      Hyperexcitability might be caused by a dysregulation of the intracortical
      GABAergic inhibitory circuitries and selective alteration of glutamatergic
      neurotransmission. Such findings suggest that motor cortex hyperexcitability and
      reorganization allows prolonged preservation of motor function during the
      clinical course of Alzheimer's disease.

PMID- 12509854
TI  - Mechanisms underlying PTEN regulation of vascular endothelial growth factor and
      angiogenesis.
AB  - Inactivation of the tumor suppressor gene PTEN and overexpression of VEGF are two
      of the most common events observed in high-grade malignant gliomas. The purpose
      of this study was to determine whether PTEN controls VEGF expression in gliomas
      under normoxic conditions. Transfer of PTEN to human glioma cells resulted in the
      transduction of a functional PTEN protein as evidenced by the upregulation of p27
      and modification of the phosphorylation status of Akt. Under normoxic conditions,
      enzyme-linked immunosorbent assay and Northern blot analyses showed
      downregulation of VEGF in PTEN-treated cells. Moreover, conditioned media from
      PTEN-treated glioma cells significantly diminished the ability of endothelial
      cells to grow and migrate. Western blot assays demonstrated that, in a normoxic
      environment, PTEN downregulates HIF-1 alpha. Finally, promoter activity assays
      showed that the VEGF promoter region containing the HIF-1alpha binding site is
      necessary and sufficient for PTEN-mediated downregulation of VEGF. Experiments
      with PI3-K inhibitors and kinase assays suggested that PI3-K is mediating the
      effect of PTEN on VEGF, and not the p42/p48 or p38 MAP kinases. These results
      indicate that restoration of PTEN function in gliomas may induce therapeutic
      effect by downregulating VEGF. Furthermore, this close functional relationship
      between PTEN and VEGF suggests that a better understanding of the transduction
      signal regulated by PTEN might enhance the knowledge of the cause and physiology
      of vascular and inflammatory diseases.

PMID- 12509855
TI  - Atypical focal MRI lesions in a case of juvenile Alexander's disease.
AB  - We present a juvenile case of Alexander's disease with atypical focal magnetic
      resonance imaging-detected lesions and elevated levels of lactate in
      cerebrospinal fluid. The diagnosis was based on the neuropathological finding of
      a diffuse accumulation of Rosenthal fibers within the brain and the spinal cord.
      The diagnosis was confirmed by detection of a mutation in exon 1 at nucleotide
      position 249 of glial fibrillary acidic protein cDNA, a finding previously
      reported in cases of infantile Alexander's disease.

PMID- 12509856
TI  - Cardiac energetics correlates to myocardial hypertrophy in Friedreich's ataxia.
AB  - Friedreich's ataxia is a neurodegenerative disease frequently associated with
      hypertrophic cardiomyopathy. We have determined mitochondrial ATP,
      phosphocreatine, and intracellular inorganic phosphate levels by 31P nuclear
      magnetic resonance spectroscopy in the heart of 11 Friedreich's ataxia patients
      and 11 healthy controls. For the first time, to our knowledge, we showed a
      significant correlation between the extent of myocardial energy deficiency and
      the degree of myocardial hypertrophy. When combining our results with previous
      works on Friedreich's ataxia, these novel findings suggest that energy metabolism
      is most likely the cause and hypertrophy the effect in Friedreich's ataxia.

PMID- 12509857
TI  - The MAZ protein is an autoantigen of Hodgkin's disease and paraneoplastic
      cerebellar dysfunction.
AB  - Probing a cerebellar expression library with TrAb sera from patients with
      Hodgkin's disease and paraneoplastic cerebellar degeneration resulted in the
      isolation of MAZ (myc-associated zinc-finger protein). Eleven of 19 TrAb sera and
      16 of 131 controls reacted with MAZ, indicating a significant, although not
      specific, association between Tr and MAZ immunities (p < 0.001). Interestingly, 9
      of 16 positive control patients also had cerebellar dysfunction. Purified MAZ
      antibodies reacted with Purkinje cells. In neuronal cells, MAZ interacts with DCC
      (Deleted in Colorectal Cancer product), the receptor for netrin-1, a neuronal
      survival factor. These findings suggest epitope spreading between the Tr antigen
      and the MAZ-DCC complex and offer a possible model of immune-mediated cerebellar
      disease.

PMID- 12509858
TI  - Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?
AB  - We identified two novel heteroplasmic mitochondrial DNA point mutations in the
      gene encoding the ND5 subunit of complex I: a 12770A-->G transition identified in
      a patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and
      stroke-like episodes) and a 13045A-->C transversion in a patient with a
      MELAS/Leber's hereditary optic neuropathy/Leigh's overlap syndrome. Biochemical
      analysis of muscle homogenates showed normal or very mildly reduced complex I
      activity. Histochemistry was normal. Our observations add to the evidence that
      mitochondrial ND5 protein coding gene mutations frequently associate with the
      MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS.

PMID- 12509859
TI  - A novel L266V mutation of the tau gene causes frontotemporal dementia with a
      unique tau pathology.
AB  - We report a novel mutation of tau (L266V missense mutation in exon 9) which may
      cause a type of familial frontotemporal dementia. The brain of a patient showed
      Pick body-like inclusions and unique tau-positive, argyrophilic astrocytes with
      stout filaments and naked, round, or irregular argyrophilic inclusions with
      deposits of both three-repeat and four-repeat tau. Recombinant tau with a L266V
      mutation showed a reduced ability to promote microtubule assembly, which may be
      the primary effect of the mutation.

PMID- 12509860
TI  - Meningioma presenting with Cushing's syndrome: an unusual clinical presentation.
AB  - We report a patient with a meningioma presenting with Cushing's syndrome, an
      unprecedented paraneoplastic presentation. Molecular studies, bioassay, and high
      performance liquid chromatography of tumor specimens demonstrated the synthesis
      and secretion of bioactive corticotropin-releasing hormone. To our knowledge,
      this appears to be the first report of a hormone-secreting meningioma and,
      further, the first clearly proven case of Cushing's syndrome due to ectopic
      corticotropin-releasing hormone secretion without concomitant corticotropin
      production.

PMID- 12509861
TI  - Peripheral nervous system complications of sickle cell disease.

PMID- 12509863
TI  - An ALS2 gene mutation causes hereditary spastic paraplegia in a Pakistani
      kindred.

PMID- 12509865
TI  - Headache as a presenting symptom in hereditary hemachromatosis [corrected].

PMID- 12509867
TI  - Small-scale pattern formation in a cortical area of the embryonic chicken
      telencephalon.
AB  - The parahippocampal area is a cortical region of the avian dorsomedial
      telencephalon. In the chicken embryo, it contains discrete clusters of cadherin-7
      positive cells, which are embedded in a cadherin-7-negative matrix. In the
      present work, the development and spatial distribution of these clusters is
      studied in whole-mount specimens. The clusters form a complex, coherent pattern
      of patches of variable size, spacing, and staining intensity. The pattern is
      especially prominent and regularly spaced in the rostral part of the caudolateral
      parahippocampal area. Here, it consists of stripes and connecting bridges with an
      average periodicity of approximately 0.3 mm. This pattern vaguely resembles some
      animal fur patterns and the ocular dominance domain of the mammalian visual
      cortex. The cadherin-7-positive patches also differ from their surrounding area
      by their cytoarchitecture and their increased acetylcholinesterase activity,
      suggesting that they represent functionally specialized subregions within the
      parahippocampal area. During development, the patchiness is first observed
      between 9 and 10 days of incubation and gradually becomes more prominent until 15
      days of incubation. Our results indicate that the patchy organization of cortical
      gray matter on a small scale of periodicity (below 1 mm), which is well studied
      in the mammalian neocortex, is also found in the avian telencephalon.

PMID- 12509868
TI  - Transient cochlear ischemia causes delayed cell death in the organ of Corti: an
      experimental study in gerbils.
AB  - To elucidate whether ischemia-reperfusion can cause delayed cell death in the
      cochlea, the effects of transient cochlear ischemia on hearing and on neuronal
      structures in the cochlea were studied in Mongolian gerbils. Ischemia was induced
      by bilaterally occluding the vertebral arteries for 5 minutes in gerbils, which
      lack posterior cerebral communicating arteries. In gerbils, the labyrinthine
      arteries are fed solely by the vertebral arteries. Occlusion of the vertebral
      arteries caused a remarkable increase in the threshold of compound action
      potentials (CAPs), which recovered over the following day. However, 7 days after
      the onset of reperfusion, the threshold began to increase again. Morphologic
      changes in the hair cell stereocilia were revealed by electron microscopy. The
      number of nuclear collapses was counted in cells stained for DNA and F-actin to
      evaluate the degree of cell death in the organ of Corti. Changes in spiral
      ganglion cell (SGC) neuron number were detected, whether or not progressive
      neuronal death occurred in the SGC. These studies showed that sporadic fusion of
      hair cells and the disappearance of hair cell stereocilia did not begin until 4
      days after ischemia. On subsequent days, the loss of hair cells, especially inner
      hair cells (IHCs), and the degeneration of SGC neurons became apparent. Ten days
      after ischemia, the mean percentage cell loss of IHCs was 6.4% in the basal turn,
      6.4% in the second turn, and 0.8% in the apical turn, respectively, and the
      number of SGC neurons had decreased to 89% of preischemic status. These results
      indicate that transient ischemia causes delayed hearing loss and cell death in
      the cochlea by day 7 after ischemia.

PMID- 12509869
TI  - Unique developmental patterns of GABAergic neurons in rat spinal cord.
AB  - Gamma-aminobutyric acid (GABA)ergic neurons have been postulated to compose an
      important component of local circuits in the adult spinal cord, yet their
      identity and axonal projections have not been well defined. We have found that,
      during early embryonic ages (E12-E16), both glutamic acid decarboxylase 65
      (GAD65) and GABA were expressed in cell bodies and growing axons, whereas at
      older ages (E17-P28), they were localized primarily in terminal-like structures.
      To determine whether these developmental changes in GAD65 and GABA were due to an
      intracellular shift in the distribution pattern of GAD proteins, we used a spinal
      cord slice model. Initial experiments demonstrated that the pattern of GABAergic
      neurons within organotypic cultures mimicked the expression pattern seen in
      embryos. Sixteen-day-old embryonic slices grown 1 day in vitro contained many
      GAD65- and GAD67-labeled somata, whereas those grown 4 days in vitro contained
      primarily terminal-like varicosities. When isolated E14-E16 slices were grown for
      4 days in vitro, the width of the GAD65-labeled ventral marginal zone decreased
      by 40-50%, a finding that suggests these GABAergic axons originated from sources
      both intrinsic and extrinsic to the slices. Finally, when axonal transport was
      blocked in vitro, the developmental subcellular localization of GAD65 and GAD67
      was reversed, so that GABAergic cell bodies were detected at all ages examined.
      These data indicate that an intracellular redistribution of both forms of GAD
      underlie the developmental changes observed in GABAergic spinal cord neurons.
      Taken together, our findings suggest a rapid translocation of GAD proteins from
      cell bodies to synaptic terminals following axonal outgrowth and synaptogenesis.

PMID- 12509870
TI  - Zonal organization of the vestibulocerebellum in pigeons (Columba livia): I.
      Climbing fiber input to the flocculus.
AB  - Previous studies in pigeons have shown that the neurons in the medial column of
      the inferior olive respond best to patterns of optic flow resulting from self
      rotation. With respect to the axis of rotation, there are two functional groups:
      rVA neurons prefer rotation about the vertical axis, whereas rH45 neurons respond
      best to rotation about an horizontal axis oriented at 45 degrees ipsilateral
      azimuth. The rVA and rH45 neurons are located in the caudal and rostral margins
      of the medial column, respectively. These olivary neurons project as climbing
      fibers to the contralateral flocculus. In this study, injections of anterograde
      tracers into the medial column were used to investigate the zonal organization of
      the climbing fiber input to the flocculus of pigeons. Iontophoretic injections of
      either cholera toxin subunit-B or biotinylated dextrin amine were made into the
      medial column of the inferior olive at locations responsive to rVA or rH45
      rotational optic flow. Anterogradely labeled climbing fibers in the flocculus
      showed a clear zonal organization. There were four parasagittal bands spanning
      both folia IXcd and X consisting of two rVA zones interdigitated with two rH45
      zones. These findings are compared with the zonal organization of the flocculus
      in mammalian species.

PMID- 12509871
TI  - Zonal organization of the vestibulocerebellum in pigeons (Columba livia): II.
      Projections of the rotation zones of the flocculus.
AB  - Previous neurophysiologic research in birds and mammals has shown that there are
      two types of Purkinje cells in the flocculus. The first type shows maximal
      modulation in response to rotational optokinetic stimulation about the vertical
      axis (rVA neurons). The second type shows maximal modulation in response to
      rotational optokinetic stimulation about a horizontal axis oriented 45 degrees to
      contralateral azimuth (rH45c neurons). In pigeons, the rVA and rH45c are
      organized into four alternating parasagittal zones. In this study we investigated
      the projections of Purkinje cells in the rVA and rH45c zones by using the
      anterograde tracers biotinylated dextran amine and cholera toxin subunit B. After
      iontophoretic injections of tracers into the rH45c zones, heavy anterograde
      labeling was found in the infracerebellar nucleus and the medial margin of the
      superior vestibular nucleus. Some labeling was also consistently observed in the
      lateral cerebellar nucleus and the dorsolateral vestibular nucleus. After
      injections into the rVA zones, heavy anterograde labeling was found in the medial
      and descending vestibular nuclei, the nucleus prepositus hypoglossi, and the
      central region of the superior vestibular nucleus. Less labeling was seen in the
      tangential nucleus, the dorsolateral vestibular nucleus, and the lateral
      vestibular nucleus, pars ventralis. These results are compared and contrasted
      with findings in mammalian species.

PMID- 12509872
TI  - Developmental relationship between cholinergic amacrine cell processes and
      ganglion cell dendrites of the mouse retina.
AB  - Ganglion cells of the mammalian retina undergo structural remodeling before their
      dendrites are confined to functionally distinct laminas within the inner
      plexiform layer. It has been proposed that cholinergic amacrine cells provide
      laminar cues that remodel ganglion cell dendrites, because their processes
      stratify before those of the ganglion cells. To address this possibility, it is
      necessary to know whether cholinergic cells contact all or only some classes of
      ganglion cells during development. We, therefore, used two-photon microscopy to
      simultaneously reconstruct the dendritic arbors of different classes of ganglion
      cells and terminal processes of cholinergic cells in neonatal mouse retina. We
      determined that, after birth, cholinergic cells contacted only a subset of
      ganglion cells. Large bistratified cells (LBCs), resembling direction selective
      ganglion cells in other species, had dendrites that fasciculated with the
      cholinergic plexuses. The LBCs received numerous presynaptic cholinergic contacts
      shortly after birth. In contrast, large monostratified cells (LMCs), ramifying
      outside the cholinergic plexuses at maturity, received few, if any, cholinergic
      contacts even at early stages when their dendrites overlapped with the
      cholinergic processes. These observations suggest that cholinergic cells provide
      laminar cues for only subsets of ganglion cells. They also indicate that the
      synaptic organization between amacrine and ganglion cells may be specified early
      in development.

PMID- 12509873
TI  - Identification of cholinoceptive glycinergic neurons in the mammalian retina.
AB  - The light-evoked release of acetylcholine (ACh) affects the responses of many
      retinal ganglion cells, in part via nicotinic acetylcholine receptors (nAChRs).
      nAChRs that contain beta2alpha3 neuronal nicotinic acetylcholine receptors have
      been identified and localized in the rabbit retina; these nAChRs are recognized
      by the monoclonal antibody mAb210. We have examined the expression of beta2alpha3
      nAChRs by glycinergic amacrine cells in the rabbit retina and have identified
      different subpopulations of nicotinic cholinoceptive glycinergic cells using
      double and triple immunohistochemistry with quantitative analysis. Here we
      demonstrate that about 70% of the cholinoceptive amacrine cells in rabbit retina
      are glycinergic cells. At least three nonoverlapping subpopulations of mAb210
      glycine-immunoreactive cells can be distinguished with antibodies against
      calretinin, calbindin, and gamma-aminobutyric acid (GABA)(A) receptors. The
      cholinergic cells in rabbit retina are thought to synapse only on other
      cholinergic cells and ganglion cells. Thus, the expression of beta2alpha3 nAChRs
      on diverse populations of glycinergic cells is puzzling. To explore this finding,
      the subcellular localization of beta2alpha3 was studied at the electron
      microscopic level. mAb210 immunoreactivity was localized on the dendrites of
      amacrines and ganglion cells throughout the inner plexiform layer, and much of
      the labeling was not associated with recognizable synapses. Thus, our findings
      indicate that ACh in the mammalian retina may modulate glycinergic circuits via
      extrasynaptic beta2alpha3 nAChRs.

PMID- 12509874
TI  - Neuron-specific age-related decreases in dopamine receptor subtype mRNAs.
AB  - Age-related decline in dopamine receptor levels has been observed in regional
      studies of animal and human brains; however, identifying specific cellular
      substrates and/or alterations in distinct neuronal populations remains elusive.
      To evaluate whether age-related decreases in dopamine receptor subtypes are
      associated with specific cell populations in the hippocampus and entorhinal
      cortex, antisense RNA amplification was combined with cDNA array analysis to
      examine effects of aging on D1-D5 dopamine receptor mRNA expression levels in
      hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells
      from post-mortem human brains (19-92 years). In CA1 pyramidal neurons,
      significant age-related decline was observed for dopamine receptor mRNAs (D1-D4,
      P < 0.001; D5, P < 0.05) but not for the cytoskeletal elements beta-actin, three
      repeat (3R) tau, and four-repeat (4R) tau. In contrast, no significant changes
      were observed in stellate cells across the same cohort. Thus, senescence may be a
      factor responsible for cell-specific decrements in dopamine receptor gene
      expression in one population of neurons within a circuit that is critical for
      learning and memory. Furthermore, these results support the hypothesis that
      alterations in dopaminergic function may also be related to behavioral
      abnormalities, such as psychosis, that occur with aging.

PMID- 12509875
TI  - Topography, cytoarchitecture, and cellular phenotypes of cortical areas that form
      the cingulo-parahippocampal isthmus and adjoining retrocalcarine areas in the
      monkey.
AB  - The monkey cingulo-parahippocampal isthmus was identified recently in the depths
      and lateral bank of the anterior calcarine fissure but was not characterized
      fully. Cytoarchitectonic and immunohistochemical results presented here reveal
      that the isthmus is composed of four cortical areas. These include the
      presubiculum of the isthmus (PrSi), parasubiculum of the isthmus (PaSi), area 29
      of the isthmus (area 29i) and area prostriata (Pro), which has anterior (Pro-a)
      and posterior (Pro-p) divisions. The PrSi, characterized by dense calbindin+
      (CB+) neuropil in layer III, merges with area 29i at approximately the middle
      portion of the isthmus; the latter lacking the CB+ neuropil. The PaSi,
      characterized by a cell-free lamina dissecans and light parvalbumin+ labeling, is
      observed in the ventral isthmus. The Pro, located posterior to area 29i and PaSi,
      and anterior to area 17, has an incipient layer IV, but the density of granule
      cells gradually increase toward area 17. Pro-a has an incipient layer IV,
      contains few SMI-32+ neurons, and adjoins area 30 dorsally. The latter also has
      an incipient layer IV but contains, in contrast, more SMI-32+ neurons. Pro-p has
      a clear but thin layer IV, contains a small number of SMI-32+ neurons, and
      adjoins both area 23 and area 18 dorsally and area 18 ventrally. Compared with
      Pro-p, area 23 contains many more SMI-32+ neurons, whereas area 18 contains far
      more SMI-32+ neurons. These findings reveal that the isthmus is a key cortical
      zone connecting both the cingulate and parahippocampal gyri, but also the limbic
      and visual cortices. Emphasizing the former only, which has been the tendency
      historically, underestimates the anatomic complexity of the isthmus, and likely,
      its functional correlates.

PMID- 12509876
TI  - Wewakazole, a novel cyclic dodecapeptide from a Papua New Guinea Lyngbya
      majuscula.
AB  - Phytochemical examination of a Papua New Guinea collection of Lyngbya majuscula
      resulted in the discovery of wewakazole (1), a novel cyclic dodecapeptide
      containing an unprecedented six five-membered heterocycles. Multiple NMR
      experiments and MS/MS data were required to assemble its planar structure because
      of its extensively signal-overlapped NMR spectra. In particular, a 1D HMBC was
      utilized to orient a three amino acid fragment that could not be placed by
      standard spectroscopic methods. [structure--see text]

PMID- 12509877
TI  - Application of aryloximes as solid-phase ketone linkers.
AB  - In both solution and the solid phase, a variety of ketone oxime anions have been
      treated with 4-substituted-2-fluorobenzonitriles to give the corresponding
      nucleophilic aromatic substitution aryloxime adducts. Under aqueous acidic
      conditions, these adducts underwent cyclization to give the corresponding
      ketones. Suzuki and amide coupling reactions were also successfully performed on
      two resin-bound oximes followed by subsequent cyclorelease to give ketone product
      in good yields and purities. [reaction--see text]

PMID- 12509878
TI  - Synthesis of new, pyrene-containing, metal-chelating lipids and sensing of cupric
      ions.
AB  - The syntheses of several saturated, pyrene-containing, metal-chelating lipids are
      described. These lipids are capable of strongly binding to transition metal ions
      employing the metal-chelating headgroup. The excimer-to-monomer ratio of the
      pyrene groups changes with addition of cupric ions to the liposomes. Three other
      transition metal ions (Zn(2+), Ni(2+), and Hg(2+)) did not cause any appreciable
      changes in the excimer-to-monomer ratio. [reaction--see text]

PMID- 12509879
TI  - Ring-opening metathesis phase-trafficking (ROMpt) synthesis: multistep synthesis
      on soluble ROM supports.
AB  - The use of ring-opening metathesis (ROM) oligomers as soluble supports for a
      multistep reaction sequence is described. A Mitsunobu reaction followed by an in
      situ ROMP-mediated phase-trafficking purification is utilized to generate soluble
      ROM oligomers that are isolated via precipitation with methanol. Once formed, the
      ROM oligomers serve as soluble supports for further solution-phase reactions,
      including a ring-closing metathesis. After each step, the support-bound products
      are isolated by precipitation with a suitable solvent. [reaction--see text]

PMID- 12509880
TI  - Free base meso-tetraaryl-morpholinochlorins and porpholactone from meso-tetraaryl
      2,3-dihydroxy-chlorin.
AB  - meso-Tetraaryl-2,3-dihydroxychlorins (1) were converted in one step to the novel
      free base macrocycles meso-tetraaryl-2,3-dialkoxy-2a-oxa-2a-homoporphyrins
      (morpholinochlorins, 3). Their bathochromically shifted chlorin-type UV-vis
      spectra indicate the presence of a nonplanar chromophore. The structure of meso
      tetratolyldiethoxymorpholinochlorin (3b), as determined by X-ray crystallography,
      was found to be largely planar, suggesting significant conformational flexibility
      of these macrocycles. Oxidation of diol 1 with MnO(4)(-) generates known
      porpholactone 4 in high yields. [reaction--see text]

PMID- 12509881
TI  - Sigma-antiaromaticity in cyclobutane, cubane, and other molecules with saturated
      four-membered rings.
AB  - Dissected nucleus-independent chemical shift (NICS) analyses of cycloalkanes and
      cage hydrocarbons reveal contrasting ring current effects, diatropic in three-
      and five-membered and paratropic in four-membered ring systems. The large
      shielding effects of the C-C bonds of the archetypal sigma-aromatic,
      cyclopropane, are magnified in tetrahedrane and related structures. The
      remarkable deshielding effect of the cyclobutane C-C(sigma) bonds is general:
      cubane and cages with four-membered rings are strongly deshielding (i.e., sigma
      antiaromatic).[structure--see text]

PMID- 12509882
TI  - Total synthesis of (-)-cassine.
AB  - The PdCl(2)-catalyzed cyclization of amino allylic alcohol 16 gave the cyclized
      product 17a with excellent diastereoselectivity. The versatility of compound 17a
      as the building block for synthesizing cis-2,6-disubstituted piperidine alkaloids
      has been demonstrated by a total synthesis of (-)-cassine (1). [reaction--see
      text]

PMID- 12509883
TI  - Pd-catalyzed allylic substitution using nucleophilic N-heterocyclic carbene as a
      ligand.
AB  - A nucleophilic N-heterocyclic carbene has been successfully used in a Pd(0)
      catalyzed allylic substitution for the first time. It was found that allylic
      substitution with a soft nucleophile using a Pd-carbene catalyst proceeds via
      retention of configuration, the stereochemical reaction pathway being the same as
      that of the reaction using a Pd-phosphine complex. [reaction--see text]

PMID- 12509884
TI  - 1,6-asymmetric induction in boron-mediated aldol reactions: application to a
      practical total synthesis of (+)-discodermolide.
AB  - By relying solely on substrate-based stereocontrol, a practical total synthesis
      of the microtubule-stabilizing anticancer agent (+)-discodermolide has been
      realized. This exploits a novel aldol bond construction with 1,6-stereoinduction
      from the boron enolate of (Z)-enone 3 in addition to aldehyde 2. The 1,3-diol 7
      is employed as a common building block for the C(1)-C(5), C(9)-C(16), and C(17)
      C(24) subunits. [reaction--see text]

PMID- 12509885
TI  - Palladium-catalyzed synthesis of carcinogenic polycyclic aromatic hydrocarbon
      epoxide-nucleoside adducts: the first amination of a chloro nucleoside.
AB  - Pd-catalyzed coupling of the axially constrained, less reactive benzo[a]pyrene
      bay-region amino benzoates, derived from the tetrahydro and diol epoxides, with C
      6 and C-2 halopurine deoxynucleosides offers an efficient approach to the
      synthesis of the corresponding nucleoside-epoxide adducts. Also reported are the
      first examples involving the coupling of a 6-chloropurine deoxynucleoside with
      these amines, a reaction that is difficult by direct halide displacement. Certain
      mechanistic aspects of this metal-catalyzed C-N bond formation are also
      discussed. [reaction--see text]

PMID- 12509886
TI  - Potassium superoxide as an alternative reagent for Winterfeldt oxidation of beta
      carbolines.
AB  - Potassium superoxide was examined as an alternative oxidation reagent for the
      Winterfeldt reaction. KO(2) was found to be superior to the original Winterfeldt
      protocol for base-sensitive substrates. [reaction--see text]

PMID- 12509887
TI  - Synthesis of biologically active dicarba analogues of the peptide hormone
      oxytocin using ring-closing metathesis.
AB  - Facile synthesis of cis and trans olefinic analogues of oxytocin 1 that have
      carbon in place of sulfur is achieved via ring-closing metathesis (RCM) on a
      resin-bound linear precursor peptide. Hydrogenation of the cis olefin, 3,
      proceeds selectively to generate the previously reported saturated derivative 5.
      Biological testing on rat uterus strips shows that cis compound 3 has an EC50
      value of 38 ng/mL (EC50 for oxytocin is 2.7 ng/mL) whereas 5 and trans olefin 4
      are less active. [reaction--see text]

PMID- 12509888
TI  - Lewis acid-catalyzed nucleophilic substitutions of propargylic and allylic silyl
      ethers with enol silyl ethers.
AB  - Nucleophilic reactions of various enol silyl ethers with carbocation species
      generated from propargyl silyl ethers by the action of a Lewis acid have been
      developed. The present method is highly useful for the introduction of allenic or
      enyne functionalities into the alpha-position of substituted ketones. [reaction-
      see text]

PMID- 12509889
TI  - Synthesis of homoallyl ethers via allylation of acetals in ionic liquids
      catalyzed by trimethylsilyl trifluoromethanesulfonate.
AB  - The chemoselective allylation of acetals using allyltrimethylsilane in ionic
      liquids is catalyzed by TMS triflate (5.0-20.0 mol %). The reaction proceeds
      smoothly at room temperature to afford the corresponding homoallyl ether in good
      yield. Since the ionic liquids are easily recovered and recycled, they are a
      useful alternative to dichloromethane, which is the commonly used solvent for
      allylations. [reaction--see text]

PMID- 12509890
TI  - A 4+3 cycloaddition approach to the synthesis of (+/-)-sterpurene.
AB  - A synthesis of the sesquiterpene sterpurene is presented. Key steps include a 4+3
      cycloaddition reaction and a quasi-Favorskii rearrangement. [reaction--see text]

PMID- 12509891
TI  - Palladium catalysts for aerobic oxidative kinetic resolution of secondary
      alcohols based on mechanistic insight.
AB  - The oxidative kinetic resolution of secondary alcohols has been accomplished
      using 1:1 complexes of PdCl(2) and N-heterocyclic carbenes. In these reactions,
      both achiral and chiral carbene ligands are used in conjunction with the chiral
      base (-)-sparteine. A general synthesis of 1:1 PdCl(2)-carbene complexes has been
      developed and is amenable to a wide range of carbene ligands. The potential of
      these complexes in aerobic oxidations is highlighted by the use of a chiral
      Pd(II) complex and the chiral base (-)-sparteine to enhance the kinetic
      resolution of a racemic alcohol. [reaction--see text]

PMID- 12509892
TI  - Concise and stereoselective synthesis of enamides and dienamides by a titanium
      mediated coupling method.
AB  - Ynamide-titanium alkoxide complexes underwent hydrolysis or addition to aldehydes
      and ketones to give single, stereodefined di- or trisubstituted enamides in good
      yields. Alternatively, coupling of a variety of alkyne-titanium alkoxide
      complexes with terminal ynamides generated amino-substituted
      titanacyclopentadienes, hydrolysis or aldehyde addition of which afforded
      stereodefined dienamides. [reaction--see text]

PMID- 12509893
TI  - Photochemical cleavage and release of carboxylic acids from alpha-keto amides.
AB  - Carboxylate groups incorporated at the position alpha to the keto carbonyl of
      alpha-keto amides 1 were photochemically cleaved in aqueous media to give
      carboxylic acids in 70-90% yields with quantum yields of 0.3. The cleavage
      coproducts were diastereomeric hemiacetals 2. Prompt release of acetate and gamma
      aminobutyrate (GABA) in buffer was observed by difference FT-IR spectroscopy upon
      355 nm laser flash photolysis. The time-constant for release of GABA was <30 ms.
      [reaction--see text]

PMID- 12509894
TI  - A general and expeditious one-pot synthesis of sulfoxides in high optical purity
      from norephedrine-derived sulfamidites.
AB  - A general and simple procedure for preparing any kind of enantiomerically
      enriched sulfoxide starting from norephedrine-derived N
      benzyloxycarbonylsulfamidite 3a is reported. After one-pot reaction of 3a with
      RMgX, HBF(4), and R'MgX, a variety of sulfoxides 6 are obtained in ee usually
      higher than 93% and isolated yields ranging between 50 and 78%. The obtained
      configuration is tunable by simply electing the order of the addition of the
      reagents. [reaction--see text]

PMID- 12509895
TI  - First synthesis of a beta(2)-homoamino acid by enantioselective catalysis.
AB  - The enantioselective conjugate addition of diethylzinc to the activated
      nitroolefin methyl 3-nitropropenoate is efficiently catalyzed by copper(I)
      complexes with BINOL-based enantiopure phosphoramidite ligands. The nitroolefin
      moiety acts as the predominant Michael acceptor, giving rise to the unambiguous
      formation of 2-alkyl-3-nitro-propanoates. Moderate to excellent
      enantioselectivities and high chemical yields are obtained. The product can
      easily be transformed into a beta(2)-homoamino acid. [reaction--see text]

PMID- 12509896
TI  - 2-Deoxy-2-iodo-beta-glucopyranosyl fluorides: mild and highly stereoselective
      glycosyl donors for the synthesis of 2-deoxy-beta-glycosides from beta-hydroxy
      ketones.
AB  - 2-Deoxy-2-iodo-beta-glucopyranosyl fluoride 14 is a highly stereoselective
      glucopyranosyl donor that may be activated under mild conditions. Application of
      this new glycosyl donor to the glycosidation reactions of a variety of acceptors
      including beta-hydroxy ketones affords beta-glycosides with high efficiency and
      stereoselectivity. [reaction--see text]

PMID- 12509897
TI  - Catalytic enantioselective epoxidation of homoallylic alcohols by chiral
      zirconium complexes.
AB  - Catalytic enantioselective epoxidation of homoallylic alcohols using Zr(Ot-Bu)(4)
      and tartrate ester (or tartramide) has been developed. In the Zr(Ot
      Bu)(4)/diisopropyl tartrate-catalyzed epoxidation, the reverse of the
      enantiofacial preference was observed, depending on the Zr/ligand ratios of 1:1
      or 1:2. [reaction--see text]

PMID- 12509898
TI  - Synthesis of the carbocyclic core of the cornexistins by ring-closing metathesis.
AB  - An advanced intermediate in the synthesis of the phytotoxins cornexistin and
      hydroxycornexistin has been synthesized. Sequential palladium-mediated sp(2)
      sp(3) fragment coupling and ring-closing diene metathesis have been used to
      construct the nine-membered carbocyclic core found in the natural products.
      [reaction--see text]

PMID- 12509899
TI  - Complete stereochemistry of tetrafibricin.
AB  - With use of the NMR databases in achiral and chiral solvents, the complete
      stereochemistry of tetrafibricin (1) has been elucidated without degradation of
      the carbon framework. [structure--see text]

PMID- 12509900
TI  - Asymmetric 1,4-addition of organosiloxanes to alpha,beta-unsaturated carbonyl
      compounds catalyzed by a chiral rhodium complex.
AB  - Highly enantioselective 1,4-addition of organosiloxanes to alpha,beta-unsaturated
      carbonyl compounds was found to be catalyzed by a chiral rhodium complex
      generated from [Rh(cod)(MeCN)(2)]BF(4) and (S)-BINAP. Both (E)- and (Z)-1-alkenyl
      groups as well as aryl groups can be introduced enantioselectively into the beta
      position of a variety of ketones, esters, and amides. [reaction--see text]

PMID- 12509901
TI  - [Association of estrogen receptor gene polymorphism with cerebral infarction, a
      case-control study].
AB  - OBJECTIVE: To explore the association between estrogen receptor (ER) gene PvuII
      and XbaI polymorphisms and cerebral infarction among Chinese Han people. METHODS:
      Samples of peripheral blood white cell were extracted among 234 patients with
      cerebral infarction, aged 63.9 +/- 10.3, and 259 controls without cerebrovascular
      disease, aged 59.2 +/- 9.2, all of Chinese Han nationality. PCR-RFLP and
      genotyping of ER PvuII and XbaI polymorphisms were performed. Multiple Logistic
      regression analysis was made to explore the risk factors for cerebral infarction.
      RESULTS: After adjustment for major confounders including age, gender, smoking,
      alcohol drinking, education, history of hypertension, diabetes mellitus, coronary
      artery disease and hyperlipoidemia, multiple Logistic regression analysis showed
      that: (1) The Pp genotype of ER PvuII polymorphism increased the risk of cerebral
      infarction significantly (OR = 1.97, 95% CI: 1.21 - 3.21); (2) The ER XbaI
      polymorphism was not in association with cerebral infarction significantly; (3)
      The PPXx/Ppxx genotypes increased the risk of cerebral infarction significantly
      (OR = 1.67, 2.52 and 2.18 respectively, P < 0.05) before or after all subjects
      were stratified by the history of hypertension or hyperlipoidemia; and (4) The
      positive interaction between the ER PvuII polymorphism and the presence of
      hypertension or diabetes or hyperlipoidemia could increase the risk of cerebral
      infarction significantly. CONCLUSION: ER gene may be one of the genetic candidate
      genes for cerebral infarction among Chinese Han population.

PMID- 12509902
TI  - [Change of serum soluble intercellular adhesion molecule and basic fibroblast
      growth factor in patients with acute cerebral infarction and its clinical
      significance].
AB  - OBJECTIVE: To explore the changes of the levels of soluble intercellular adhesion
      molecule-1 (sICAM-1) and basic fibroblast growth factor (bFGF) in serum of
      patients with acute cerebral infarction, and the effects of sICAM-1 and bFGF on
      cerebral infarction. METHODS: ELISA was used to detect the serum sICAM-1 and bFGF
      of 55 patients with acute cerebral infarction (within 2 days) as well as 32
      patients diagnosed as with other neurologic diseases (20 patients with sciatica
      and 12 with trigeminal neuralgia) and 30 healthy persons as controls. RESULTS:
      (1) Both serum sICAM-1 and bFGF in the infarction group were significantly higher
      [(766.2 +/- 178.8) micro g/L and (17.4 +/- 8.2) micro g/L respectively] than in
      other disease control group [(529.6 +/- 76.7) micro g/L and (8.3 +/- 2.8) micro
      g/L respectively] and normal control group [(520.7 +/- 115.9) micro g/L and (5.8
      +/- 2.7) micro g/L respectively] (P = 0.000). (2) Correlation analysis showed
      that there was a positive correlation between the level of serum sICAM-1 and bFGF
      (r = 0.471, P = 0.000), the level of sICAM-1 was also positively correlated with
      the number of leukocytes at acute stage (r = 0.285, P = 0.035), and a negative
      correlation between sICAM-1 and European stroke scale (r = -0.333, P = 0.013) was
      found. No significant correlation was observed between the level of sICAM-1 and
      the levels of serum cholesterol (r = -0.042, P = 0.758) or triglyceride (r =
      0.061, P = 0.675). (3) Blood pressure seemed to have no influence on the content
      of sICAM-1 and bFGF after cerebral infarction, while the level of serum bFGF with
      large infarct size was obviously higher at acute stage. CONCLUSION: The levels of
      sICAM-1 and bFGF increase significantly in the patients with acute cerebral
      infarction. sICAM-1 and bFGF mayin participate in the pathophysiologic process
      through inflammatory mechanism. The detection of serum sICAM-1 will be helpful in
      estimating the clinical severity and the determination of bFGF will be helpful in
      estimating the size of infarct lesion at acute stage of cerebral infarction.

PMID- 12509903
TI  - [Study on the origin of aberrant clones with chromosome abnormalities in MDS].
AB  - OBJECTIVE: To study the origin of aberrant clones with chromosome abnormalities
      in MDS. METHODS: Antibodies recognizing myeloid cells (CD33), B cells (CD19) and
      T cells (CD2) were used to sort bone marrow cells of ten MDS patients with
      chromosome abnormalities (trisomy 8 five cases, trisomy 8 accompanying trisomy 9
      one case, trisomy 8 accompanying 7p- one case, 20q- two cases, t (1; 7) one case)
      by Immuno-Magnetic Bead technique, then the positive cells for CD33, CD19 or CD2
      were detected respectively by interphase FISH using the centromeric probes for
      chromosomes 1, 7and 8, and the locus specific probe for 20q12. 200 to 300 cells
      were scored for each detection. RESULTS: FISH showed that trisomy 8, t (1; 7) and
      20q- all affected CD33 positive cells, but not CD2 positive cells in these ten
      MDS patients. Only in one MDS patient, 20q- affected the CD19 positive cells.
      CONCLUSION: Our data suggest that the chromosomal aberrations in MDS are mostly
      restricted to myeloid cell lineages, but B lymphocytes are involved in minor MDS
      implying that abnormal clone originated from a multipotent hematopoietic
      progenitor.

PMID- 12509904
TI  - [Application of bilateral internal mammary artery in coronary artery bypass
      grafting].
AB  - OBJECTIVE: To evaluate the effects of application of bilateral internal mammary
      artery grafts in coronary artery by pass grafting (CABG). METHODS: From Jan. 1998
      to Mar. 2001, 51 patients with coronary arteriosclerotic cardiopathy, all males,
      aged 36 - 65 (average 49.9 years), underwent coronary artery bypass grafting with
      bilateral internal mammary artery grafts. The pathologic change involved three
      branches of coronary artery in 48 cases and involved the left main trunk in 3
      cases. 37 patients had the history of myocardial infarction. Four cases were
      complicated by left ventricular aneurysm. 47 cases were operated upon on-pump and
      4 off-pump. Left ventricular aneurysmectomy was done in 4 patients and coronary
      endarterectomy in 1 patient. The patterns of anastomosis were as follows: right
      internal mammary artery (RIMA) to left anterior descending artery (LAD) and left
      internal mammary artery (LIMA) to obtuse marginal (OM) in 39 cases, LIMA to LAD
      and RIMA to right coronary artery (RCA) in 9 cases, and LIMA to LAD and RIMA to
      OM in 3 cases. Gastroepiploic artery and left radical artery were used in other
      bypass grafting. The average number of grafts used for each case was 3. RESULTS:
      There were 3 early operative deaths, with an early operative mortality rate of
      5.9%. One patient died of low output syndrome due to perioperative myocardial
      infection, 1 patient died of refractory arrhythmia, and 1 patient died of
      cerebral accident 40 days after operation. Intraaortic balloon pump was used in 4
      cases post-operatively. Mediastinal infection occurred in 2 patients. The
      patients were followed up for 2 to 39 months (average 15.5 months). During the
      follow-up, no angina pectoris occurred and ultrasonography showed that the
      bilateral internal mammary artery grafts were unobstructed in all patients.
      CONCLUSION: Bilateral internal mammary artery grafts can be applied effectively
      in CABG with a good short-term effect, especially for young patients.

PMID- 12509905
TI  - [Comparative study of three kinds of outflow tract reconstruction of hepatic
      veins in piggyback liver transplantation].
AB  - OBJECTIVE: To study the effects of 3 different operational patterns of piggyback
      liver transplantation (PBLT) used to reconstruct backflow of hepatic veins.
      METHODS: Sixty-three operations of PBLT were performed on 59 patients with
      terminal hepatic diseases after three operational patterns: EEAT [the
      suprahepatic inferior vena cava (sup-H-IVC) of donor is anstomosed with the
      plasticized hepatic vein of recipient end-to-end, also called standard PBLT,
      SPBLT] in 17 cases, ESAT (the sup-H-IVC of donor is anastomosed with the sup-H
      IVC of recipient end-to-side) in 12 cases, and SSAT [the retrohepatic IVC (RHIVC)
      of donor is anastomosed with the RHIVC of recipient side-to-side] in 32 cases,
      the latter two patterns being called ameliorative PBLT (APBLT) jointly. The
      effects were analyzed. RESULTS: Complications, such as backflow obstruction of
      hepatic vein and delayed recovery of liver function, were observed in the EEAT
      and ESAT groups, but not in the SSAT group. CONCLUSION: The SSAT pattern of PBLT
      is easy to perform and advantageous to avoid the technical maladies of the other
      2 patterns and postoperative complications, and provides assurance of recovery
      after operation.

PMID- 12509906
TI  - [Surgical management of laryngeal cancer and preservation of laryngeal function].
AB  - OBJECTIVE: To explore the surgical methods for laryngeal cancer and long-term
      effects of larygectomy. METHODS: 625 cases of laryngeal cancer at different
      stages, including 182 cases of supraglottic cancer, 429 cases of glottic cancer,
      and 14 cases of subglottic cancer, underwent operation of different kinds from
      1979 to 1999. Radiotherapy was given to those with poorly differentiated squamous
      carcinoma or with metastasis of cervical lymph nodes postoperatively. The effects
      of operation, especially that on the preservation of laryngeal function was
      analyzed. RESULTS: Partial laryngectomy was performed on 521 of the 625 cases
      (83.4%) and 203 of the 305 cases at stages III and IV (66.6%). The decannulation
      rate was 84.07% in the cases undergoing partial laryngectomy. The nasal feeding
      tube was removed and peroral feeding was recovered in all patients. All cases
      undergoing partial laryngectomy succeeded in phonation. The overall 3-year
      survival rate was 89.63% and the overall 5-year survival rate was 77.36%. For the
      cases with laryngeal cancer at stages III and IV, the 3-year survival rate among
      those undergoing partial laryngectomy was 84.9%, not significantly different from
      that among those cases undergoing total laryngectomy (87.7%, P > 0.05); the 5
      year survival rate was 66.6% among those undergoing partial laryngectomy and was
      69.7% among those undergoing totals laryngectomy (P > 0.05). CONCLUSION: The rate
      of partial laryngectomy is rather high in this group. It is possible to preserve
      the laryngeal function without compromising the remote survival rate. The
      prerequisite for the preservation of laryngeal function is to master and choose
      the proper renovation methods.

PMID- 12509907
TI  - [Tinnitus retraining therapy: a clinical control study of 117 patients].
AB  - OBJECTIVE: To investigate the clinical effects of tinnitus retraining therapy
      (TRT) on tinnitus. METHODS: 225 tinnitus patients were divided into two groups.
      117 patients in the TRT group were treated with TRT and drugs, and 108 patients
      in the control group were treated with only tinnitus masking and drugs. The TRT
      is consisted of four strategies: (1) tinnitus masking with low level and broad
      band noise; (2) deep relaxation of the whole body; (3) diversion of the attention
      to other things; and (4) psychological counseling and therapy. Drugs, such as
      vasodilator, neurotrophic drug, and sedative of the similar dose and duration of
      pharmacotherapy were administered to the 2 groups. Effect evaluation was
      conducted thrice 2, 6, and 12 months after the beginning of therapy to see if the
      tinnitus was attenuated or disappeared and if the patients' emotion, sleep, and
      work were disturbed by tinnitus. RESULTS: The relief rate was 17.09%, 82.05%, and
      88.03% in the TRT group 2, 6, and 12 months after respectively; and 2.78%,
      26.85%, and 41.6% in the control group 2, 6, and 12 months after respectively
      (chi(2) = 12.54, 69.30, and 63.64, all P < 0.01). CONCLUSION: TRT is effective in
      treatment of tinnitus.

PMID- 12509908
TI  - [Identification of new mutant sites and 894C deletion variant genotyping of HIV-1
      coreceptor CCR5 in indigenous Chinese populations].
AB  - OBJECTIVE: To investigate the new single nucleotide polymorphism (SNP) sites of
      HIV-1 coreceptor CCR5 gene and conduct genotyping of CCR5-894C deletion allele in
      Chinese populations. METHODS: The full length fragment of CCR5 gene coding region
      was amplified by PCR amplification and sequenced in 45 healthy subjects from Han
      ethnic group. The sequencing data was analyzed by using DNAstar software for
      identification of new SNP sites. Furthermore, the genotyping of CCR5-894C
      deletion variant was performed by PCR-RFLP assay in 627 indigenous Chinese
      individuals including HIV-1 carriers, HIV-1 high risk population of STDs or IDUs
      as well as normal contrast. RESULTS: Totally six SNPs and one cytosine base
      deletion at the 894 nucleotide of CCR5 gene coding region were found in forty
      five Chinese Han subjects. Four SNPs, i.e. 184A-->G, 503G-->T, 668G-->A, 999G-
      >T, cause alteration of corresponding amino acids in CCR5 protein and two SNPs
      are nonsense mutations. The 894C deletion mutation results in a frame shift
      mutation of CCR5 gene. Among the six SNPs identified, the three sites 184A-->G,
      503G-->T, 999G-->T were firstly reported only in Chinese people. The allelic
      frequencies of mutant 184G, 503T and 999T alleles were 1.1%, 21.1% and 10.0% in
      Han healthy subjects, respectively. PCR-RFLP assay showed the frequencies of CCR5
      894C deletion alleles are 1.11%, 0.53% and 0% for Chinese Han, Tibetan and
      Mongolian healthy individuals, respectively. There was not significant different
      of the frequencies of CCR5-894C deletion allele among HIV-1 high risk
      populations, HIV-1 carries and healthy subjects. CONCLUSION: The subjects from
      Chinese Han group has its own distinctive SNP sites in the HIV-1 coreceptor CCR5
      gene, three new SNPs (184A-->G, 503G-->T, 999G-->T) were firstly identified.
      Taking together, the significance and implication of these distinctive SNP sites
      and the 894C deletion mutation in the pathogenesis of HIV/AIDS disease need to be
      further studied.

PMID- 12509909
TI  - [The role of urotensin II gene in the genetic susceptibility to type 2 diabetes
      in Chinese population].
AB  - OBJECTIVE: To investigate the relationship between the polymorphism of site
      rs228648 in urotensin II gene and the genetic susceptibility to type 2 diabetes
      in Han people. METHODS: Genotyping was conducted to investigate the polymorphism
      of site rs228648 (G-A) in urotensin II gene among 166 unrelated type 2 diabetic
      subjects (case group 1), 87 probands from 87 families of type 2 diabetics (case
      group 2), and 121 non-diabetic normal controls (control group). RESULTS: 1) The
      frequency of "G" allele of site rs228648 was 62.3% and 75.3% in case group 1 and
      case group 2 respectively, significantly higher than that in the control group
      (50.4%, P = 0.004 and P < 0.001). 2) The frequency of G/G genotype of rs228648
      was 35% and 53% in case group 1 and case group 2 respectively, significantly
      higher than that in the control group (24%, P < 0.05 and P < 0.01). The odds
      ratio was 1.86, P = 0.041 in the case group 1 and 4.03, P < 0.001 in the case
      control 2 after adjustment by sex, age and BMI. CONCLUSION: Urotensin II gene may
      contribute to the genetic susceptibility to type 2 diabetes in Han population.

PMID- 12509910
TI  - [Extended-spectrum beta-lactamase in Klebsiella pneumoniae and Escherichia coli
      isolates].
AB  - OBJECTIVE: To investigate the prevalence, drug resistance, gene typing, and
      epidemicity of extended-spectrum beta-lactamases (ESBL) Klebsiella pneumoniae and
      Escherichia coli isolates. METHODS: 559 strains of K. pneumoniae and 427 strains
      of E.coli were isolated form Huanshan Hospital from 1 January to 31 December
      1999. The ESBL-producing strains were detected by double disc test and confirmed
      by minimal inhibitory concentration (MIC). The MIC of ESBL-producing strains was
      detected by agar dilution test. The beta-lactamase genes were detected by PCR.
      DNA fingerprinting was made by pulsed-field gel electrophoresis (PFGE). RESULTS:
      The incidence of ESBL-producing strains was 51% among the isolated K. pneumoniae
      (285/559) and 23.6% among the isolated E. coli (101/427), most of which were
      collected from the patients in the intensive care unit and neurosurgical ward.
      63.5% of the ESBL-producing K. pneumoniae strains were collected from sputum
      specimens, and 64.3% of the ESBL-producing E. coli strains were collected from
      the urine specimens. Most ESBL-producing strains were resistant to most beta
      lactam antibiotics, including the third-generation cephalosporins, and non- beta
      lactam antimicrobial drugs, such as fluoroquinolones, aminoglycosides,
      tetracycline, and chloramphenicol. Most of the ESBL-producing strains were
      susceptible to imipenam, cefmetazole, and beta-lactam antibiotic/clavulanic acid.
      TEM type beta-lactamase was the main type among those EBSL-producing strains,
      followed by SHV type and CTX-M type. Some ESBL-producing E. coli and most ESBL
      producing K. pneumoniae produced more than one type of beta-lactamase.
      CONCLUSION: ESBL-producing strains are common among hospital strains of E. coli
      and K. pneumoniae. Most of them are multidrug resistant. Prevalence and
      transmission of these strains exist in hospital.

PMID- 12509911
TI  - [Effect of IFN-gamma and TNF-alpha on hepatitis B virus posttranscriptional
      regulatory elements].
AB  - OBJECTIVE: To explore the effect of IFN-gamma and TNF-alpha on hepatitis B virus
      posttranscriptional regulatory elements. METHODS: The objective eukaryotic
      expression vectors were constructed by molecular cloning and PCR-based site
      directed mutagensis in vitro, and identification was performed using PCR and
      sequencing analysis. CAT assays were performed by using ELISA kit. RESULTS: The
      eukaryotic expression vectors containing HPRE segment and mutating point were
      constructed successfully as confirmed by sequencing analysis. The normalized CAT
      activity from recombinant pDM138 and control produced in transfected cells
      incubated in the absence of cytokine were 896 +/- 214 and 37 +/- 11 pg/ml,
      respectively. After incubation with IFN-gamma, TNF-alpha and IFN-gamma + TNF
      alpha, the normalized CAT activity from recombinant pDM138 produced in
      transfected cells were 324 +/- 57, 396 +/- 82 and 175 +/- 36 pg/ml, respectively
      (t = 5.19,4.39, 6.68, P < 0.01). The effect of IFN-gamma and TNF-alpha were dose
      dependent over a range of 0 to 1,000 U/ml. CONCLUSION: The expression of HBV gene
      may be regulated by IFN-gamma and TNF-alpha through inhibiting the function of
      HPRE.

PMID- 12509912
TI  - [Bystander effect mediated by herpes simplex virus-thymidine kinase/ganciclovir
      approach on prostatic cancer cells and its regulation].
AB  - OBJECTIVE: To estimate the bystander effect mediated by herpes simplex virus
      thymidine kanase/ganciclovir (HSV-TK/GCV) suicide gene therapy approach on PC-3m,
      a prostate cancer cell line, to explore the role of connexin (Cx) mediated gap
      junctional intercellular communication (GJIC) in the procedure of bystander
      effect of HSV-TK/GCV system and to investigate the modulation of apigenin, a Cx
      expression up-regulator on the connexin43 (Cx43) expression and GJIC of PC-3m
      cells. METHODS: PC-3m cells were cultured and PC-3m cells transfected with EBV
      based expression vector containing HSV-TK gene (TK(+) PC-3m cells) and TK(-) PC
      3m cells were mixed at the ratio of 1:9. GCV was added into the mixture. The
      bystander effect was evaluated by MTT assay. GJIC and HSV-TK/GCV induced
      bystander effect in several typical cell lines, such as NIH-3T3, Cos-7, and L-02
      cells, were determined by crape loading dye tracing (SLDT) and MTT assay
      respectively. Cx43 mRNA expression and inherent GJIC capacity of PC-3m cells were
      examined by RT-PCR and SLDT. TK(+) PC-3m cells and TK(-) cells were mixed and
      divided into 4 groups and added with GCV, apigenin, apigenin + GCV, and apigenin
      + GCV + 18-alpha-glycyrrhetinic acid (AGA) respectively. Then the killing rate on
      PC-3m cells was examined by MTT. RESULTS: After 72 h treatment of 100 micro mol/L
      GCV on the mixture of wild-type PC-3m cells and HSV-TK gene modified PC-3m cells,
      only 23.5% +/- 3.2% cells were killed. The magnitude of HSV-TK/GCV bystander
      effect were more powerful in NIH-3T3, Cos-7, and L-02 cells which manifested
      excellent GJIC than in ACHN and HeLa cells (P < 0.001). Expression of Cx43 mRNA
      was shown by RT-PCR, however, it is weaker than that in ACHN cells and normal
      prostate tissue. With the administration of apigenin, the expression of Cx43 mRNA
      and the GJIC function of PC-3m cells were increased by 2.2 times (P < 0.01) The
      enhancing effect of apigenin on GJIC function of PC-3m cells lasted 48 hours and
      could be inhibited by addition of AGA. Apigenin of the concentration of 10 micro
      mol/L could obviously improve the bystander effect of TK system on PC-3m cells (P
      < 0.001). The killing rate of GCV on the mixed PC-3m cells was 59.86% +/- 2.44%,
      and was only 25.34% +/- 2.89% with the addition of AGA. CONCLUSION: There is a
      positive correlation between the magnitude of bystander effect mediated by HSV
      TK/GCV approach and the potency of internal GJIC in the target cells. Down
      regulated Cx43 expression and disrupted inherent GJIC potential of PC-3m cells
      result in the poor magnitude of HSV-TK/GCV bystander effect. Chemical agent like
      apigenin up-modulates Cx43 expression and invokes GJIC capacity of PC-3m cells,
      thus enhancing the bystander effect and augmenting the efficacy of TK suicide
      therapy.

PMID- 12509913
TI  - [Regulation of lipopolysaccharide-induced inducible nitric oxide synthase gene
      expression by protein kinase C].
AB  - OBJECTIVE: To explore the molecular mechanism of inducible nitric oxide synthase
      (iNOS) gene expression induced by lipopolysaccharide (LPS) in monocytes or
      macrophages. METHODS: Luciferase report gene vector pGL2iNOSLuc driven by murine
      iNOS promoter region was constructed using gene recombination technique. RAW264.7
      cells were cultured and transfected with luciferase report gene vector
      pGL2iNOSLuc. Twenty four hours later, PKC inhibitor H-7, calcium channel blocker
      verapamil, was added into the culture. LPS or PKC activator PMA was added 2 hours
      later to stimulate the cells. The activity of beta-galactosidase and luciferase
      was examined and the relative luciferase activity, representing the iNOS
      transactivity, was calculated. Modified Griess method was used to measure the
      concentration of NO(2)(-)/NO(3)(-) in the culture so as to evaluate the effect of
      PKC inhibitor on NO production induced by LPS. RT-PCR was used to study the
      effect of LPS on iNOS gene expression in RAW264.7 cells. RESULTS: Thirty minutes
      after stimulation of RAW264.7 cells by LPS, the activity of PKC in cytomembrane
      increased and the activity of PKC in cytoplasm decreased significantly in
      comparison with the baseline levels (P < 0.01). The NO concentration was 30.1
      micro mol/L +/- 5.4 micro mol/L 12 hours after the stimulation of LPS on RAW264.7
      cells, and was much more higher 24 and 48 hours after, all significantly higher
      than before (all P < 0.01). The NO concentration in the supernatant with H-7 at
      any time point was significantly lower than those in corresponding samples
      without H-7 (all P < 0.01). After stimulation of LPS and PMA, the relative
      luciferase activity was 25.3 +/- 4.6, significantly higher than the baseline
      level (P < 0.01). H-7 and verapamil significantly inhibited the LPS-induced iNOS
      transactivity (both P < 0.01). iNOS mRNA expression was increased greatly, and H
      7 significantly inhibited this expression 12, 24, and 48 hours after LPS
      stimulation. CONCLUSION: In RAW264.7 cells, LPS stimulation increases
      intracellular calcium and activates PKC, thus inducing iNOS gene expression that
      contributes to the production of NO, which is an important signaling mechanism of
      NO production in septic shock.

PMID- 12509914
TI  - [Construction and characterization of bispecific single-chain antibody fragments
      SZ-2/SZ-21 against platelet glycoprotein Ib alpha and beta3].
AB  - OBJECTIVE: To generate bispecific single-chain Fv (bis-scFv) antibody fragment SZ
      2/SZ-21 against platelet glycoprotein (GP) Ib alpha and GP IIIa. METHODS: The SZ
      2/SZ-21 bispecific single-chain antibody expression vector pET22-21-L-2scFv was
      constructed by gene recombination technique with a interdomain linker fragment,
      SZ-21 single-chain antibody (anti- GP IIIa) gene and SZ-2 single-chain antibody
      (anti- GP Ib alpha) gene, identified by sequencing, and introduced into
      Escherichia coli strain BL21 (DE3) Plys. The bispecific protein accumulated in
      bacteria as insoluble inclusion bodies was harvested, denatured, refolded, and
      affinity-purified in vitro. SZ-2/SZ-21 bispecific single-chain antibody was added
      into platelet-rich plasma (PRP) and the binding of SZ-2/SZ-21 bispecific single
      chain antibody with platelets was examined by histochemistry and cytometry,
      ELISA, or Western blotting. Restocetin, ADP, or thrombin was added into PRP with
      SZ-2/SZ-21 bispecific single-chain antibody to observe the platelet aggregation.
      RESULTS: The expression vector pET22-21-L-2scFv was correctly constructed. Its
      recombinant protein was expressed mostly in the form of inclusion bodies, and the
      yield accounted for 14% of the total cell protein. The bispecific protein could
      bind to platelet. The platelet aggregation induced by restocetion, ADP, or
      thrombin in PRP with SZ-2/SZ-21 bispecific single-chain antibody was
      significantly reduced. CONCLUSION: An SZ-2/SZ-21 bispecific single-chain antibody
      against two target antigens in platelet was developed and characterized with the
      ability to inhibit platelet aggregation induced by restocetin, ADP, and thrombin.

PMID- 12509915
TI  - [Clinical phenotypes of hereditary nonpolyposis colorectal cancer in Chinese
      population].
AB  - OBJECTIVE: To investigate the clinical phenotypes of hereditary nonpolyposis
      colorectal cancer (HNPCC) in Chinese population. METHODS: Data of 34 HNPCC
      families diagnosed according to Armsterdam II Criteria and Japan Criteria,
      including age of diagnosis, site of cancer inclusive of abenteric cancer, history
      of synchronous and/or metachronous colorectal cancer, histopathology of tumor,
      clinical manifestations, and genealogy were collected and analyzed. RESULTS: Out
      of the 612 members aged over 18 of these 34 families 140 persons were diagnosed
      as HNPCC patients with 154 cancer foci, 93 males and 47 females. The median age
      of confirmed diagnosis of HNPCC was 45.3 years. 62.1% of them developed the
      cancer before the age of 50 and 87.1% of them developed the cancer before the age
      of 60. Out of the 154 primary cancer foci, 31 were extracolonic (20.1%),
      including synchronous and/or metachronous cancers, with gastric cancer accounting
      for 41.9% (13/31), and 123 were colonic cancers (79.9%). Out of the 116 cases of
      colorectal cancer, there were 77 cases of proximal colon cancer (66.4%) and 39
      cases of distal colon cancer (33.7%). There were 11 cases of synchronous and/or
      metachronous cancer (7.86%). The main clinical manifestations included
      hematochezia, anemia, abdominal mass, and abdominal pain. CONCLUSION: In
      comparison with the facts among Westerners, HNPCC occurred earlier; the
      proportions of proximal colon cancer, extracolonic cancer, and synchronous and/or
      metachronous cancers are larger; and gastric cancer accounts for a greater
      percentage among Chinese.

PMID- 12509916
TI  - [Loss of heterozygosity of tumor suppressor genes at chromosome 3p in
      transitional cell carcinoma of urinary bladder].
AB  - OBJECTIVE: To investigate the potential effects of three tumor suppressor genes
      located at chromosome 3p, FHIT, hMLH1 and VHL, in carcinogenesis of transitional
      cell carcinoma (TCC) of urinary bladder in Chinese. METHODS: PCR was used to
      examine the heterozygosity and loss of heterozygosity (LOH) of the 6
      microsatellite polymorphic markers inside of or flanking to the three genes tumor
      suppressor genes FHIT, hMLHi, and VHL in TCC tissues of 40 cases. RESULTS: The
      rates of heterozygosity and LOH were 55.0% (38/40) and 59.1% (22/38) for hMLH1
      gene. The rates of heterozygosity and LOH were 90.0% (36/40) and 47.2% (17/36).
      The rate of heterozygosity of the two microsatellite polymorphic markers in the
      intron of FHIT gene, D2S1234 and D3S1300, were 70% (28/40) and 67.5% (27/40), The
      LOH rates of D2S1234 and D3S1300 were 46.4% (13/28) and 37% (10/27) respectively.
      The rate that at least one the these 2 microsatellite polymorphic markers was
      heterozygote was 95.0% (38/40), the rate that LOH occurred for at least one of
      them was 57.8% (22/38). The heterozygosity rate of D3S1561 and D3S1612, two
      microsatellite polymorphic markers linked to hMLH1 gene, were 42.5% (17/40) and
      30% (12/40) respectively, the LOH rates for these two markers were 41.2% (7/17)
      and 75.0% (9/12) respectively, the rate that at least one of these two markers
      was heterozygote was 59.1% (13/22). The heterozygosity rate of D3S10368 and
      D3S1284, two microsatellite polymorphic markers linked to VHL gene, were 70%
      (28/40) and 47.5% (19/40) respectively, the LOH rates for these two markers were
      42.8% (12/28) and 42.1% (8/19) respectively, the rate that at least one of these
      two markers was heterozygote was 90.0% (36/40). High frequencies of LOH were
      found in tumor suppressor genes FHIT, hMLH1 and VH. Only the LOH of D3S1284 was
      positively correlated with the pathological staging of TCC of urinary bladder (P
      < 0.05). CONCLUSION: LOH in tumor suppressor genes FHIT, hMLH1 and VHL may play
      an important role in carcinogenesis of human urinary bladder, and may provide new
      approaches for early detection of TCC. Loss of VHK gene may be a late event of
      carcinogenesis of TCC.

PMID- 12509917
TI  - [Involvement of heparanase in human abdominal aortic aneurysm].
AB  - OBJECTIVE: To determine whether heparanase might participate the formation of
      abdominal aortic aneurysms (AAA) and explore a novel pathogenesis for it.
      METHODS: Total RNA was extracted from 20 tissue samples of human infrarenal
      abdominal aortic aneurysm (AAA) and 5 samples of normal aorta (NA), all resected
      in operation, and 5 samples of primary hepatocellular carcinoma. Northern blot
      was used to evaluate the expression of heparanase. Immunohistochemistry and
      computer-assisted image analysis were used to assess the expression of heparanase
      and its substrate heparan sulfate proteoglycan protein (HSGP) and microvessel
      hyperplasia. RESULTS: Semi-quantitative analysis showed that the expression of
      heparanase in AAA was significantly higher than that in normal abdominal aorta (P
      < 0.01), but equivalent to that in primary hepatocellular carcinoma (P > 0.05).
      However, the expression of HSPG was lowered in AAA and was significantly
      negatively correlated with the expression of heparanase and microvessel density.
      Both of heparanase and HSPG were mainly located in adventitia and intima of AAA
      walls. CONCLUSION: Heparanase participates in the structure damage and remodeling
      of abdominal aorta at matrix level, which contributes to AAA formation.

PMID- 12509918
TI  - [Diagnosis and treatment of glomus jugulare tumor].
AB  - OBJECTIVE: To investigate the clinical features, diagnosis, and treatment of
      glomus jugulare tumor. METHODS: The data of 37 patients of glomus jugulare tumor
      diagnosed by digital subtraction angiography (DSA) and/or operation and
      pathology, 14 males (37.8%) and 23 females (62.2%), with an average age of 37.2
      (3.5 approximately 66 years) and an average course of 4.3 years (1 month - 19
      years), were analyzed. RESULTS: The tumor was located in the left ear in 19
      cases, in the right ear in 17 cases, and in both ears in 1 case, totally 38 ears.
      The tumor was chromaffin in one case with hypertension. One case was complicated
      by ipsilateral carotid body tumor, and 2 cases were complicated by ipsilateral
      cholesteatoma. Thirty cases (81.1%) presented pulsatile tinnitus and hearing loss
      as the main symptoms. Thirteen cases (35.1%) were diagnosed as glomus jugulare
      tumor at the first visit, and 24 cases (64.9%) were diagnosed as other diseases
      with an average misdiagnosis period of 4.4 years. Eighteen tumors originated from
      typanum and 28 tumors from glomus jugulare. According the Fisch classification
      1981, the tumors in 11 ears were type A, in 7 ears were type B, in 7 ears type C,
      in 5 ears type D1, and in 8 ears type D2. All cases, except the one with
      bilateral lesions, underwent operation. The tumor was completely resected in 30
      cases. Postoperatively, facial paralysis was seen in 6 cases, dizziness,
      hoarseness, and subauricular necrosis was seen in one case respectively. Of the
      25 patients followed up with a mean follow-up time of 5.2 years (1.1 - 16.1
      years), 3 died of lung cancer, neuroblastoma, or extensive involvement of glomus
      jugulare tumor respectively, 19 survived without tumor, and 3 survived with the
      tumor. CONCLUSION: Glomus jugulare tumor is likely to involve surrounding
      important tissues, and to be misdiagnosed. Early surgical removal of the lesion
      is important.

PMID- 12509919
TI  - [Primary study of diaphragmatic electromyography in amyotrophic lateral sclerosis
      patients].
AB  - OBJECTIVE: To investigate the features and application of diaphragmatic
      electromyography (DEMG) in amyotrophic lateral sclerosis (ALS) patients. METHODS:
      We recorded the electromyography of 43 diaphragms from 43 ALS patients by
      inserting concentric needle electrode from intercostal space, when they held
      their breath, breathed smoothly and drew deep breath, and took electromyography
      of 22 healthy diaphragms as controls. The percentage of forced vital capacity
      (%FVC) was performed simultaneously in 28 ALS patients. RESULTS: All subjects
      showed no side-effect. The spontaneous activities could be found when ALS
      patients held their breath. During the period of their smooth breath, the
      duration of their diaphragmatic motor unit action potential (DMUAP) (12.1 ms +/-
      2.7 ms) was longer than those of controls, and the common logarithmic value of
      the amplitude (2.585 +/- 0.132) and the area (2.722 +/- 0.208) of DMUAP were
      larger than those of controls. The percentage of polyphasic (53%) and satellite
      potential (5%) was also increased in ALS patients. The duration (13.6 ms +/- 3.6
      ms) of the ALS patients with clinical dyspnoea was longer than that (11.6 ms +/-
      2.2 ms) of others without it. The spontaneous activities were correlated with
      clinical dyspnoea and %FVC. CONCLUSION: DEMG with needle electrode could evaluate
      the respiratory state of ALS patients at the level of electrophysiology. The
      duration and the spontaneous activity were its sensitive indexes.

PMID- 12509920
TI  - [Insulin-like growth factor-I and cognitive function in patients with obstructive
      sleep apnea syndrome].
AB  - OBJECTIVE: To explore the possible biochemical mechanism of cognitive impairment
      in patients with obstructive sleep apnea syndrome (OSAS). METHODS:
      Polysomnography was administered to thirty-six patients with OSAS and eighteen
      education and BMI-matched controls, all males aged 40 approximately 49 for 8.5
      hours at night. Early next morning blood was drawn and serum insulin-like growth
      factor-I (IGF-I) was determined by immunoradiometric assay. Then
      neuropsychological tests of visual regeneration, digital symbol, comprehensive
      memory and digital span were conducted. RESULTS: The quality of sleep in the
      patients with OSAS was significantly worse than that of the controls. The score
      of visual regeneration in the patients with OSAS was 8.4 +/- 2.7, significantly
      lower than that in control group (11.6 +/- 1.4, P < 0.01). The score of digital
      symbol in patients with OSAS was 36.92 +/- 8.31, significantly lower than that in
      the controls (47.8 +/- 6.8, P < 0.01). The serum IGF-I level of the patients with
      OSAS was: 127.2 +/- 87.0 ng/ml, significantly lower than that of the controls
      (194.03 ng/ml +/- 77.31 ng/ml, P < 0.05). The IGF-I level was significantly
      positively correlated with the scores of visual regeneration test (r = 0.381, P <
      0.05) and digital symbol test (r = 0.330, P < 0.05), lowest SaO(2) (r = 0.371, P
      < 0.05), mean SaO(2) (r = 0.333, P < 0.05) and REM sleep duration (r = 0.598, P <
      0.01). CONCLUSION: Decrease of serum IGF-I level may play a role in the cognitive
      impairment in patients with OSAS. Nocturnal hypoxemia and REM sleep deprivation
      may be the reason of the decrease of the serum IGF-I level in patients with OSAS.

PMID- 12509921
TI  - [T-lymphocyte immune in HIV-infected people and AIDS patients in China].
AB  - OBJECTIVE: To study the T-lymphocyte immune alterations and its clinical
      significance in HIV-infected persons and AIDS patients in China. METHODS:
      Peripheral blood samples were collected from 13 HIV-infected persons, 27 AIDS
      patients, and 51 healthy blood donors (controls) and then labeled with monoclonal
      antibodies. Flow cytometry was used to detect the count of CD4(+) T-lymphocytes,
      CD8(+) T-lymphocytes, and its different subsets including the naive cell subset
      (CD4(+) CD45RA(+) CD62L(+)), activated cell subsets (CD4(+) HLA-DR(+), CD8(+) HLA
      DR(+), CD8(+) CD38(+)), functional cell subsets (CD4(+) CD28(+)), and apoptotic
      cell subsets (CD4(+) CD95(+), CD8(+) CD95(+)). The plasma HIV loading was also
      detected. RESULTS: The CD4(+) cell count was (849 +/- 288) x 10(6)/L in the
      control group, significantly higher than that in HIV-infected person group [(437
      +/- 184) x 10(6)/L, P < 0.01], and that in AIDS patient group [(50 +/- 51) x
      10(6)/L, P < 0.01]. The CD8(+) cell count was (579 +/- 175) x 10(6)/L in the
      control group, significantly lower than that in HIV-infected person group [(1 031
      +/- 345) x 10(6)/L, P < 0.05], and not significantly different from that in AIDS
      patient group (535 +/- 338) x 10(6)/L, with a significant difference between the
      HIV-infected person group and AIDS patient group (P < 0.05). The percentage of
      CD4(+) CD45RA(+) CD62L(+) were 43.0% +/- 11.4% in the control group, not
      significantly different from that in HIV-infected person group (44.2% +/- 12.8%),
      but significantly higher than that in AIDS patient group (24.8% +/- 15.5%, P <
      0.05). The CD4(+) CD45RA(+) CD62L(+) cell count was (368 +/- 162) x 10(6)/L in
      the control group, significantly higher than those in HIV-infected person group
      [(185 +/- 134) x 10(6)/L] and in AIDS patient group [(18 +/- 20) x 10(6)/L, both
      P < 0.01] with a significant difference between the HIV-infected person group and
      AIDS patient group (P < 0.01). The percentage of CD4(+) CD28(+) was 93.1% +/-
      8.1% in the control group, significantly higher than those in HIV-infected person
      group (62.6% +/- 28.2%) and in AIDS patient group (56.9% +/- 26.4%) with a
      significant difference between any two groups (all P < 0.01). The percentages of
      CD4(+) HLA-DR(+), CD8(+) HLA-DR(+), and CD8(+) CD38(+) in the AIDS patient group
      were higher than those in the HIV-infected person group and control group with
      significant difference between any two groups (all P < 0.01). The percentages of
      CD4(+) CD95(+) and CD8(+) CD95(+) in the AIDS patient group were not
      significantly different from that in control group, but significantly higher than
      that in HIV-infected person group (P < 0.05). The plasma HIV loading was 3.74 +/-
      0.78 lg copies/ml in the HIV-infected person group and was 4.94 +/- 0.68 lg
      copies/ml in AIDS patient group (P < 0.05), and the count of CD4(+) cells and
      CD4(+) CD45RA(+) CD62L(+) cells were obviously negatively correlated with the
      plasma HIV loading (r = -0.796, r = -0.750, P < 0.01). CONCLUSION: The T
      lymphocyte immune dysfunction occurring in HIV-infected persons and AIDS patients
      in China involves not only the number, but also the function and activation of T
      lymphocytes. Synthetical analysis of the alterations of different T cell subsets
      reflects the immune deficiency and severity of disease more comprehensively than
      pure examination of the amounts of CD4(+) and CD8(+) cells.

PMID- 12509922
TI  - [Relation of pentanucleotide repeat polymorphism of apolipoprotein (a) gene to
      plasma lipoprotein (a) level among Chinese patients with myocardial infarction
      and cerebral infarction].
AB  - OBJECTIVE: Investigate the distribution and characteristics of 5'pentanucleotide
      TTTTA repeat (PNTR) polymorphism of apolipoprotein (a) [apo (a)] gene among
      Chinese patients with myocardial infarction (MI) and cerebral infarction, and its
      relationship to plasma lipoprotein (a) [Lp (a)] level. METHODS: DNA was extracted
      from the peripheral blood of 438 patients with myocardial infarction (MI,
      documented angiographically) and 218 controls, and 809 patients with cerebral
      infarction (documented by CT) and 1 817 controls. Plasma Lp (a) level was
      measured by ELISA. PNTR polymorphism of apo (a) gene was determined by polymerase
      chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis. RESULTS:
      Eight alleles and 29 genotypes in apo (a) PNTR were detected in the four groups.
      The frequency of (TTTTA)(4 - 7) allele in the cerebral infarction group was 7.0%,
      significantly higher than that in control group (5.4%, P < 0.05). The frequency
      of genotype (TTTTA)(5/8) in MI group was 13.2%, significantly higher than that in
      the control group (7.8%, P < 0.05). No significant difference was seen in other
      alleles and genotypes among different groups (all P > 0.05). The level of
      triglyceride (TG) in patients with MI was 5.13 mmol/L +/- 1.15 mmol/L,
      significantly higher than that in controls (4.90 mmol/L +/- 0.99 mmol/L, P <
      0.05). The level of TG in patients with cerebral infarction was 1.84 mmol/L +/-
      1.36 mmol/L, not significantly different from that in controls (1.83 mmol/L +/-
      1.51 mmol/L). The level of total cholesterol (TC) in patients with MI was 4.85
      mmol/L +/- 1.04 mmol/L, significantly lower than that in controls (4.97 mmol/L +/
      1.00 mmol/L, P < 0.001). The level of TC in patients with cerebral infarction
      was 1.97 +/- 1.11 mmol/L, not significantly different from that in controls (1.79
      mmol/L +/- 1.23 mmol/L). A negative correlation between the number of PNTR and Lp
      (a) level was observed in both MI group (P < 0.001) and cerebral infarction group
      (P < 0.01), and not in the control group. Small fragment repeat of apo (a) PNTR
      was correlated with cerebral infarction (OR = 1.4, 95% CI: 1.040 approximately
      1.910), not significantly with MI (P > 0.05). Multiple logistic regression
      analysis showed that individuals with plasma Lp (a) > 300 mg/L had higher risk of
      MI (OR = 2.4, 95% CI: 1.630 - 3.594), and a higher risk of cerebral infarction
      (OR = 1.6, 95% CI: 1.013 - 2.021) after adjustment for age, sex, SBP, DBP, BMI,
      smoking, TC, TG, HDL-C, LDL-C and Glu. CONCLUSION: Plasma Lp (a) is an
      independent risk factor for MI and cerebral infarction. PNTR of apo (a) gene was
      negatively correlated with Lp (a) levels both in MI group and cerebral infarction
      group. Association with PNTR genotype was only found in cerebral infarction, but
      not in MI.

PMID- 12509923
TI  - [Identification of mutations in the arginine vasopressin receptor 2 gene in
      congenital nephrogenic diabetes insipidus patients].
AB  - OBJECTIVE: To investigate the mutations of arginine vasopressin receptor 2
      (AVPR2) gene in congenital nephrogenic diabetes insipidus (NDI) patients.
      METHODS: Genomic DNA was extracted from the blood samples of 7 congenital NDI
      patients, all males, and 24 of their family members. The 6 fragments of AVPR2
      gene were amplified by PCR. The gene mutations were preliminarily screened by
      SSCP and further confirmed by DNA sequencing. RESULTS: 5 types of mutation and 8
      mutant sites of AVPR2 gene were found in 6 of the 7 patients. Two cases were
      found to have 2 different sites of mutation in the AVPR2 gene. In 4 cases new
      mutation sites not reported previously in the literature, i.e., g.469-493del 24,
      g.541insT, g.462delC and g.935T > C, were identified, resulting in the change of
      AVPR2 proteins, including A37-L44del (deletion mutation), A61G 190X (insertion
      frame-shift and nonsense mutation), P34R 36X (deletion frame-shift and nonsense
      mutation) and C192R (missense mutation). Among the 24 family members examined
      only one, a mother, was found to have an AVPR2 gene mutation with the same
      mutation site as the proband. CONCLUSION: Four novel mutation sites have been
      identified in the AVPR2 gene among the congenital NDI patients. PCR-SSCP and DNA
      sequencing can be used to preliminarily screen and diagnose gene mutation among
      congenital NDI patients.

PMID- 12509924
TI  - [Serum IgA(1) from patients with IgA nephropathy induces phosphorylation of
      extracellular signal-regulated kinase and proliferation of human mesangial
      cells].
AB  - OBJECTIVE: To study the effects of serum IgA(1) from patients with IgA
      nephropathy (IgAN) on the phosphorylation of extracellular signal-regulated
      kinase (ERK) and proliferation of human mesangial cells (HMC). METHODS: Serum was
      taken from 10 IgAN patients and 10 healthy persons. IgA(1) was isolated with
      jacalin column, and then heated to become aggregated form (aIgA(1)). Primary HMCs
      were cultured and the cells of third or fourth generation were used in the test.
      HMCs were incubated with aIgA(1) from IgAN patients or from healthy persons. To
      do blocking test 50 micro mol/L PD98059 was added into the culture of HMC of the
      3 groups while the HMCs were in the relatively stationary phase. The
      phosphorylation of ERK was evaluated by Western blot; cell cycle was examined by
      DNA fluorescence labeling and flow cytometry. HMC number was counted. RESULTS: 1)
      Both the aIgA(1) from patients with IgAN and that from healthy persons induced
      the phosphorylation of ERK, DNA synthesis and proliferation of HMC in a time
      dependent manner and with a similar trend, however, the effects of aIgA(1) from
      patients with IgAN were much stronger and longer. The incubation times for the
      maximum effect on phosphorylation of ERK were 15 minutes, 24 - 36 hours, and 48 -
      72 hours in the IgAN patient group, healthy person group, and the control group
      with a ratio of phosphorylated ERK/total ERK of 49.5% +/- 10.1%, 30.7% +/- 4.4%
      and 10.5% - 12% respectively (P < 0.05). 2) After 18-hour incubation, the
      percentages of cells at the stage S were 3.48% +/- 0.54%, 6.64% +/- 0.96%, and
      7.85% +/- 0.71% in the control group, healthy person group, and IgAN patient
      group. 24 hours after incubation, the percentages of cells at stage S-G(2)-M were
      9.4% +/- 1.86% in the control group, significantly lower than that in the healthy
      person group (14.5% +/- 0.7%, P < 0.05) and that of the patient group (17.2% +/-
      0.3%, significantly higher than the other 2 groups, P < 0.01 and P < 0.05). At
      the peak time, the cells at stage S-G(2)-M accounted for 33.0% +/- 0.3% and 30.7%
      +/- 0.7% in the patient group and healthy person group respectively (P < 0.05)
      with the HMC count of (57.8 +/- 2.5) x 10(4)/ml and (50 +/- 1.5) x 10(4)/ml (P <
      0.05) respectively. After 48, 72, and 96-hour incubation with aIgA(1) the HMC
      counts were (51.7 +/- 1.6) x 10(4)/ml, and (56.4 +/- 2.6) x 10(4)/ml, and (58.8
      +/- 1.8) x 10(4)/ml, and (65.8 +/- 2.9) x 10(4)/ml, (60.0 +/- 1.7) x 10(4)/ml and
      (66.8 +/- 2.0) x 10(4)/ml in the patient group with and without pre-incubation of
      PD98059 respectively (P < 0.05). However, the HMC count was not significantly
      changed in the healthy person group. Blocking of ERK with PD98059 could inhibit
      the effect of aIgA(1) from patients with IgAN on the proliferation of HMC but
      could not inhibit the effects of aIgA(1) from healthy controls. CONCLUSION:
      IgA(1) induces the phosphorylation of ERK, DNA synthesis and proliferation of
      HMC, and the effects of IgA(1) from patients with IgAN are stronger than that
      from healthy persons.

PMID- 12509925
TI  - [Synergetic effect of mitogen-activated protein kinase pathway on expression of
      tumor necrosis factor alpha gene in RAW 264.7 cells induced by
      lipopolysaccharide].
AB  - OBJECTIVE: To explore the molecular mechanism of the synergetic effect of mitogen
      activated protein kinase (MAPK) pathway on expression of tumor necrosis factor
      alpha (TFG-alpha) gene in murine monocyte (RAW264.7 cells) induced by
      lipopolysaccharide (LPS). METHODS: RAW264.7 cells were cultured, transfected with
      vectors with mutants of different constitutively active MAPK kinases, i. e., ERK,
      JNK, and p38, vectors with inactivated mutants of MAPK kinase, and murine TNF
      alpha driven report gene pGL2TNFLuc, and then stimulated by LPS. Protein kinase
      assay was used to analyze the activity of MAPKs. Western blotting was used to
      detect the amount of target proteins. RT-PCR was used to detect the influence of
      the MEK/REK inhibitor PD98059, JNK inhibitor SP600125, and p38 inhibitor SB203580
      on the expression of TNF-alpha gene induced by LPS. RESULTS: ERK1, JNK1, and p38
      MAPKs were transiently activated by LPS. After the vectors with activated MAPK
      mutants were co-transfected with murine TNF-alpha driven report gene pGL2TNFLuc
      into RAW264.7 cells, the transcription activity of TNF-alpha promoter was induced
      to different degrees. After the vectors with inactivated MAPK mutants were co
      transfected with murine TNF-alpha driven report gene pGL2TNFLuc into RAW264.7
      cells, the transcription activity of TNF-alpha promoter was inhibited.
      CONCLUSION: The transactivity of TNF-alpha promoter stimulated by LPS involves
      ERK, JNK, and p38 pathways. These three major MAPK pathways exert synergetic
      effects on the gene regulation of TNF-alpha expression.

PMID- 12509926
TI  - [Proliferation and location of Hantaan virus in gamasid mites and chigger mites,
      a molecular biological study].
AB  - OBJECTIVE: To study the proliferation and location of Hantaan virus (HV) in
      gamasid mites and chigger mites and the significance of gamasid mites and chigger
      mites as vectors of transmission of hemorrhagic fever with renal syndrome (HFRS).
      METHODS: Gamasid mites collected from the nests of wild rodents and chigger mites
      collected from the bodies of wild rodents and thick growth of grass in the field
      were raised. Two oligonucleotide primers were developed based on the gene
      fragments of cDNA of HV 76 - 118 strain to be used in RT-PCR. RNA was extracted
      from the suspension of the gamasid mites from the nests where rodents no HV had
      been found in whose lungs lived and from the unfed larvae of chigger mites, being
      formed groups of 5, 10, 30, or 50 individuals. RT-PCR was conducted to detect the
      HV-RNA in such suspension. The larvae, nymphs, and imagines of both kinds of
      mites were ground to make suspension at an interval of 20 days. Vero-E(6) cells
      were inoculated to measure the titer of 50% tissue culture infective dose
      (TCID(50))/ml of HV. Frozen sections of larvae, nymphs, and imagines of both
      kinds of mites were made. RT-PCR and in situ hybridization were conducted to
      detect the distribution of HV-positive particles. Monoclonal antigen technique
      was used to compare the antigenicity of the HV-RNA from the rodents, mites, and
      patients from the same epidemic areas. RESULTS: HV-RNA was detected in gamasid
      mites and chigger mites. Except in the larvae of chigger mites 60 days after
      collection, titers of HV were detected and increased gradually in mites at
      different stages of life cycle. HV-RNA positive particles were detected in the
      epithelial cells of midgut and ovary, with the signal denser and more numerous in
      nymphs than in larvae. The genotypes of HV from rodents, mites and patients in
      the same endemic areas were identical: HTN type virus. CONCLUSION: HV can be
      transmitted transstadially and proliferated in mites, gamasid mites and chigger
      mites play the role of vectors of transmission for HFRS.

PMID- 12509927
TI  - [Influence of escharectomy and skin grafting during early burn stage on acute
      phase response in severely burned rats and its significance].
AB  - OBJECTIVE: To investigate the influence of escharectomy and skin-grafting during
      early burn stage on the production of acute-phase reactants by the liver in
      severely burned rats. METHODS: Ninety-six Wistar rats were randomly divided into
      three groups: normal control group (C), escharectomy on postburn day (PBD) 1
      group (0) and escharectomy on PBD4 group (F). 30% III degrees (total body surface
      area full-thickness) burn injury was caused by immersing the back in boiling
      water for 10 seconds. Escharectomy and skin grafting with cryopreserved
      allogeneic skin were performed one day or 4 days after the burn injury. ON days
      1, 2, 4, 5 and 7 after burn injury blood was withdrawn from the abdominal aorta
      of 8 rats for each experimental group. The serum contents al-antitrypsin (AT), al
      acid glycoprotein (AGP), C-reactive protein (CRP), albumin (Alb), and transferrin
      (Trf) were measured by turbidimetry. RESULTS: Significant increase in
      concentrations of positive acute-phase reactant, CRP, AGP, and AT, was observed
      in group O and group F as compared with normal control, (P < 0.05), while the
      concentrations of negative acute-phase reactants, Alb and Trf, decreased markedly
      (P < 0.05). The serum concentrations of AT and AGP in group O began to decrease
      significantly on PBD 5 and PBD7 respectively in comparison with that of the group
      F (P < 0.05), however, they still maintained a rather higher levels on PBD7. The
      concentration of CRP in group O began to decrease on PBD4, and the values on
      PBD4, 5, and 7 were significantly lower than those of the group F (P < 0.05). The
      concentration of CRP in PBD1 group reached the normal level on PBD7, however, the
      concentration of CRP in group F kept increasing till PBD5, and remained
      significantly higher than that in group C (P < 0.05). The concentration of Alb in
      group O was significantly higher on PBD7 than that in group F (P < 0.05). The
      concentration of Trf in group O on PBD5 and PBD7 was significantly higher than
      those in group F (P < 0.05). CONCLUSION: Escharectomy and skin grafting during
      early burn stage attenuates acute-phase response after burn injury and are
      beneficial to the organism.

PMID- 12509928
TI  - [Safety of gene therapy within cochlea, experimental study with guinea pig].
AB  - OBJECTIVE: To observe the safety of inoculation of recombinant adenovirus with
      human neurotrophin-3 (Ad-NT3) into cochlea and its effect on hearing function.
      METHODS: Twenty healthy guinea pigs were randomly divided into two groups: ten
      animals were inoculated with Ad-NT3 into the perilymphatic space after a small
      hole was drilled in the bony wall near tympanic scala of the base turn, while the
      other ten were introduced with artificial perilymphatic fluid (APF) as controls.
      Auditory brainstem response (ABR) were recorded before, immediately after and
      seven days after the inoculation. Seven days after the surgery, the animals were
      killed. Frozen sections and colloidin sections of cochlea were made and observed
      under microscope. Immunohistochemistry was used to detect the expression of NT3
      protein in cochlea. RESULTS: The mean ABR threshold values were (35 +/- 3.7) dB
      SPL and (35 +/- 3.2) dB SPL before the inoculation, (40 +/- 2.5) dB SPL and (40
      +/- 3.0) dB SPL immediately after the inoculation, and (35 +/- 3.0) dB SPL and
      (35 +/- 3.0) dB SPL seven days after inoculation in the Ad-NT3 group and AFP
      group respectively (all P > 0.05). The ABR-III latency of 100dB SPL click was
      (2.812 +/- 0.087) ms and (2.824 +/- 0.121) ms before inoculation, (2.793 +/-
      0.093) ms and (2.796 +/- 0.095) ms immediately after inoculation, and (2.822 +/-
      0.102) ms and (2.834 +/- 0.135) ms seven days after inoculation in Ad-NT3 and AFP
      groups respectively (P > 0.05). No difference of ABR threshold and latency was
      observed at different time points in both groups. Ad-NT3 protein was expressed
      within each turn of the cochlea, including spiral limbus, spiral ligament and
      ganglion cells. The cochlear structure remained intact with no sign of infection
      or cell degeneration. CONCLUSION: Gene therapy by means of introduction of trace
      AdNT3 into the perilymphatic space through pore in tympanic scala is safe,
      causing no structure change or hearing loss.

PMID- 12509929
TI  - [Impact of islet alpha cell loss on insulin secretion].
AB  - OBJECTIVE: To investigate the impact of islet alpha cell loss on insulin
      secretion. METHODS: Human pancreatic tissues underwent over-digestion of
      collagenase. Digestion was terminated in half of the tissue suspension, and half
      of the suspension was put into solution of collagenase to undergo over-digestion
      so as to cause loss of islet alpha cells. The tissues of digested human pancreas
      and over-digested human pancreas were fixed and immunohistochemical staining was
      made to observe the loss of islet alpha cells. The contents of insulin and
      glucagon in solutions of normal human pancreas, human islet of pancreas with
      normal enzyme secretion, and over-digested human islet were measured by
      radioimmunoassay. The ratios of insulin/glucagon in these three solutions were
      calculated so as to analyze the loss of alpha cells. Different human pancreatic
      tissues were inoculated in 24-well plate. Glucose solutions of different
      concentrations were added into the suspensions. The concentration of insulin in
      the supernatant was measured after incubation. C57/BL Normal human pancreas and
      human pancreas with islet alpha cell loss were transplanted into the renal
      capsules of two groups of 5 C57/BL mice with experimental diabetes mellitus
      respectively. The blood insulin was measured for two days. On the 3(rd) day, the
      left kidneys of the mice were taken to undergo insulin/glucagon
      immunohistochemical staining to observe the loss of alpha cells. Human islets
      with alpha cell loss were transplanted into the renal capsules of another 10
      mice. Then 5 of them received injection of normal saline and the other 5 received
      glucagon for 7 days, then glucagon was injected into the mice of normal saline
      group, and vise versa. The blood sugar was measured every day. RESULTS: Glucagon
      immunohistochemistry showed alpha cell loss from islet periphery in over-digested
      human pancreas. The insulin/glucagons ratios were 100:2.34 and 100:2.05 in the
      normal pancreas and isolated normal islets respectively, and was 100:0.314 in the
      over-digested islets, showing a loss of > 80% of alpha cells. As compared with
      normal islets, glucose-induced insulin secretion was significantly decreased. The
      insulin concentration was 222.7 micro U/ml +/- 32.1 micro U/ml in the suspension
      of cultured normal pancreatic cells and was 124.6 micro U/ml +/- 12.6 micro U/ml
      in the supernatant of suspension of pancreatic islets with alpha cell loss (P <
      0.01). The average blood sugar was 8.9 micro U/ml +/- 1.98 micro U/ml in mice
      grafted with normal islets and was 21.3 micro U/ml +/- 2.2 micro U/ml in mice
      grafted with alpha cell deficient islets (P < 0.01). However, insulin secretion
      in islets with alpha cell loss was significantly improved by exogenous glucagon
      in vitro and in vivo. CONCLUSION: The function of insulin secretion in islets
      with alpha cell loss is significantly decreased. Insulin secretion of islets with
      alpha cell loss can be improved by exogenous glucagon.

PMID- 12509930
TI  - [Microarray study of vasculogenic mimicry in bi-directional differentiation
      malignant tumor].
AB  - OBJECTIVE: To explore if vasculogenic mimicry (VM) exists in bi-directional
      differentiation malignant tumor. METHODS: New sections were made from 158
      paraffin sections of bi-directional malignant tumors, including malignant
      melanoma (n = 60), synoviosarcoma (n = 39), rhabdomyosarcoma (n = 29), malignant
      mesothelioma (n = 26), and epithelioid sarcoma (n = 4). The representative points
      in the paraffin sections were labeled and two tissue microarrays were made, one
      including 60 cases of malignant melanoma, and the other including the other
      tumors. Immunohistochemical staining of platelet-endothelial cell adhesion
      molecule (CD31 antigen) and periodic acid Schiff (PAS) staining were conducted.
      Microscopy was made and the areas of vessel-like channels consisted of CD31
      antigen-positive tumor cells and of PAS positive material were calculated.
      RESULTS: PAS positive material or CD31 positive material were observed in these
      bi-directional tumor cells. In the tumors vessel-like channels could be found,
      made of PAS positive material lined with CD31 negative tumor cells and red blood
      cells inside the channel, or made of tumor cells with CD31 positive material. The
      area of the former vessel-like channels was significantly smaller than that of
      the latter (P < 0.01). VM was found in 16 of the 39 cases of the highly malignant
      synoviosarcoma and acinar type rhabdomyosarcoma, a ratio higher than that among
      the cases of synoviosarcoma and acinar type rhabdomyosarcoma with lower
      malignancy (5/29) (P < 0.05). CONCLUSION: VM exists in bi-directional
      differentiation malignant tumors.

PMID- 12509931
TI  - [Application of epiglottis in laryngeal reconstruction].
AB  - OBJECTIVE: To observe the application value of epiglottis in laryngeal
      reconstruction after partial laryngectomy. METHODS: The data of 168 patients, 25
      with supraglottic carcinoma (T1N0 2, T2N0 10, T2N1 1, T2N2 1, T3N0 7, T3N2 1,
      T4N0 2, and T4N2 1), 140 with glottic carcinoma (T1N0 36, T1N1 1, T2N0 52, T2N1
      1, T2N2 1, T3N0 40, T3N2 2, T4N0 6, and T4N2 1), and 3 with subglottic carcinoma
      (T3N0 1, and T4N0 2), who underwent partial laryngectomy from 1982 to 1999 were
      summarized. The choice of surgical procedure was decided on the pathology of the
      larynx. Epiglottis was used in larynx reconstruction. RESULTS: Out of the 168
      cases, 135 cases were decannulated with a decannulation rate of 80.36%, regained
      deglutation, recovered all laryngeal functions, and resumed normal diet. None
      presented complication of accidental aspiration. The 3-year and 5-year survival
      rates were 89.48% and 74.14% respectively. CONCLUSION: Epiglottis has many
      advantages in laryngeal reconstruction.

PMID- 12509932
TI  - [A pilot study of G-CSF mobilized allogeneic bone marrow cells plus peripheral
      blood stem cells transplantation for malignant hematological diseases].
AB  - OBJECTIVE: To study the feasibility and clinical outcome of granulocyte-colony
      stimulating factor (G-CSF) mobilized allogeneic bone marrow (G-BM) plus G-CSF
      mobilized peripheral blood stem cells (G-PBSC) transplantation for malignant
      hematological disease. METHODS: G-BM plus G-PBSC transplantation was conducted
      between siblings or between parent and child. G-CSF was injected hypodermically
      into 14 stem cell donors 5 micro g x kg(-1) x d(-1) for 4 approximately 6 days.
      On the 3rd day after beginning of G-CSF injection bone marrow blood was extracted
      from the posterior superior iliac spine of the donors; on the 4th day G-PBSCs
      were collected. The collected stem cells were transplanted immediately into the
      bodies of the 14 patients with hematological disease, including acute myelocytic
      leukemia, acute lymphocytic leukemia, multiple myeloma, myelodysplastic syndrome
      and severe aplastic anemia. The clinical outcomes, including the rate of
      engraftment, speed of engraftment, and the occurrence of acute graft versus host
      disease (aGVHD) and chronic graft versus host disease (cGVHD) were investigated.
      RESULTS: All patients got endurable engraftment. The median time of recovery of
      neutrophil count to >or= 1 x 10(9)/L was 14 days (range 12 approximately 18
      days). The median time to achieve a platelet count >or= 20 x 10(9)/L without
      transfusion was 13 days (range 11 approximately 65 days). Seven of the 14
      patients developed aGVHD, 4 being in the grade I and 3 being in grade II. Three
      of the evaluable 9 patients developed extensive chronic GVHD. Two patients died
      of relapsed leukemia. One patient received secondary PBSCT from hte same donor
      because of ill engraftment and developed grade IV GVHD and died. The other 11
      patients were still alive and event-free with a median follow-up duration of 455
      days (range 84 approximately 715 days). CONCLUSION: An effective treatment for
      malignant hematological disease, G-CSF mobilized allogeneic bone marrow plus
      peripheral blood stem cells transplantation provides rapid and sustained
      engraftment without increase in incidence of aGVHD and cGVHD.

PMID- 12509933
TI  - [Pemphigus patient with pulmonary fungal infection caused by Ochroconis
      gallopava: the first case report in China].
AB  - OBJECTIVE: To report a case of pemphigus complicated by pulmonary infection due
      to Ochroconis gallopava, the first such case in China. METHODS: A male pemphigus
      patient with pulmonary symptoms, aged 68, received a needle biopsy under CT scan.
      The materials obtained from the lung cavity were cultured on Sabouraud dextrose
      agar in four test tubes. RESULTS: Fungal colonies of the same characteristics
      grew on the slant of the 4 test tubes 3 days after culture. The colonies were
      brown-green with a downy surface. Diffuse red-brown pigment was seen in the
      reverse side of the culture medium. Microscopy revealed septate and clavate
      mycelia and two-celled conidia with the apical cell being wider than the basal
      cell. The fungus was identified as Ochroconis gallopava by Dr A.A. Padhye (CDC).
      Amphotericin B liposome was given at hte dose of 50 approximately 75
      approximately 100 mg/d for more than one month Then itraconazole was given for
      about one year. The cavity in the lung became smaller in diameter and the
      symptoms were ameliorated soon after pharmacotherapy. Examination about one year
      later showed fibrosis. CONCLUSION: Case of pulmonary fungal infection caused by
      Ochroconis gallopava has been reported for the first time in China. Amphotericin
      B liposome has good effect on infection of Ochroconis gallopava.

PMID- 12509934
TI  - [Human embryonic stem cell lines preliminarily established in China].
AB  - OBJECTIVE: To establish embryonic stem (ES) cell lines from human fertilized ovum
      in China. METHODS: Fourteen human oocytes obtained from a volunteer were cultured
      in Earlg's medium and fertilized in vitro. Four of the morulae formed from the
      fertilized ovi were frozen and five continued to develop into blastocysts. The
      pellucid zones of the 5 blastocysts were removed and their inner cell masses
      (ICM) were taken out and inoculated onto the feeder layer of mouse embryonic
      fibroblasts inactivated with mitomycin C. The cell clones formed from the three
      surviving ICM were selected and dispersed mechanically and the cells were
      inoculated onto new feeder layers to produce more cell clones. When multiple
      clones were produced, they were dissociated with dispase into smaller cell masses
      which were inoculated onto new feeder layer again for subculturing. During
      different periods of cell culture, alkaline phosphatase activity (AKP) staining,
      stem cell surface marker test, and karyotyping were conducted. The suspension of
      stem cells subcultured for 5 months were inoculated to the legs of severe
      combined immunodeficiency (SCID) mice subcutaneously to observe the teratoma
      formation. RESULTS: Out of the 9 fertilized oocytes, 5 developed into
      blastocysts. The ICM of three from the five blastocysts survived and developed
      into embronic stem cell lines, named CHE1, CHE2, and CHE3 respectively. These
      stem cells remained undifferentiated after subculturing for 7 months. The stem
      cell line CHE3 had been grown for 40 passages in vitro, CHE1 for 36 passages, and
      CHE2 for 32 passages. AKP staining was positive at the passages 5, 15, and 30 for
      the 3 cell lines. The surface markers of human stem cell, SSEA-4, SSEA-3, TRA-1
      60, and GCTM-2 were positive at passage 25, 30, 40 for CHE3, and at the passages
      21, 22 and 30 for CHE1 and CHE2. But all cell lines did not express SSEA-1, a
      marker for mouse ES cells. All cell lines stably retained a normal karyotype.
      After routine passage by 5 months, human ES cells from 3 cell lines were injected
      subcutaneously into SCID mice. Six weeks after inoculation of the 3 cell lines
      teratomas were formed in all mice. Histological examination revealed that they
      contained various tissues derived from all three embryonic germ layers.
      CONCLUSION: Human embryonic stem cell lines were successfully established in
      China.

PMID- 12509935
TI  - [Cell transplantation of 5-aza cytidine induced bone marrow stromal cells
      transfected by angiogenin gene ex vivo into infarcted myocardium, an experimental
      study].
AB  - OBJECTIVE: To investigate the effect of transfection of 5-aza cytidine (5-aza)
      induced BMSCs that were transfected with Ad. ANG ex vivo into infarcted
      myocardium. METHODS: Lewis rat BMSCs were cultured in vitro and incubated
      together with 5-aza (3 micro mol/l) for 24 hours, and the induced BMSCs were
      transfected with Ad. ANG with a infection multiple of 50. ELISA method was
      applied to assay the expression and secretion of ANG in the medium. Then such
      BMSCs expressing ANG were transplanted into the ischemic myocardium of 14 Lewis
      rats whose left descending branch of coronary artery had been ligated 4 weeks ago
      (Group I). Eight rats with infarcted myocardium were transplanted with such BMSCs
      too (group II). Another eight rats received only Ad. ANG injection (group III).
      Twelve rats receiving serum-free medium injection were used as controls (Group
      IV). Four weeks after the ligation of LDA (for group I) and 4 weeks after the
      beginning of experiment (for all groups), the parameters of heart function, such
      as ejection fraction (EF) and end-diastole volume of left heart (EDLV), were
      examined by echocardiography. Four weeks after the beginning of experiment, the
      rats were killed, and the survival and differentiation of transplanted BMSCs and
      angiogenesis were observed by immunohistochemistry and transmission electron
      micrography. RESULTS: One day after the beginning of experiment, the
      concentration of ANG in the supernatant of medium was 162 +/- 10 pg/ml,
      significantly higher than that in the supernatant of medium in control group (86
      +/- 5 pg/ml, P < 0.01). The concentration of ANG gradually increased and reached
      its peak at the 4th to 7th day; ANG could still be assayed 15 days later. 4 weeks
      after the transplantation, most of the 5-aza-induced BMSCs in group I and group
      II had differentiated into cardiomyogenic cells in the transplanted area. The EF
      value was 0.42 +/- 0.114 weeks after ligation of LAD, and was 0.69 +/- 0.034
      weeks after the transplantation in group I. The EF value was 0.46 +/- 0.06 at the
      beginning of experiment and was 0.64 +/- 0.144 weeks after the transplantation in
      group II. The improvement of EF in Group I was significantly than that in other 3
      groups (P < 0.05 or P < 0.01). The number of new vessels in group I was 36.3/high
      power field (HPF), significantly higher than those in the other three groups
      (10.5/HPF in Group II, 23.1/HPF in Group III, and 0.9/HPF in Group IV).
      CONCLUSION: Induced by 5-aza, BMSCs differentiate into cardiomyogenic cells in
      infracted myocardium. ANG-expressing BMSCs transplantation is one of the safe and
      beneficial new strategies for repairing damaged myocardium and enhancing
      angiogenesis in ischemic myocardium.

PMID- 12509936
TI  - [Site-directed mutagenesis of atrial natriuretic peptide gene and effect of the
      mutations on its diuretic activity in nephrotic rats].
AB  - OBJECTIVE: To prolong the half-life and enhance the biological activity of the
      human atrial natriuretic peptide (hANP), a peptide hormone, which is synthesized
      and released mainly by cardiac atrial myocytes and possesses potent natriuretic,
      diretic, and vasorelaxant properties. METHODS: The site-directed mutation
      technique based on polymerase chain reaction was performed to get the mutant of
      the human ANP gene (mhANP), and the retroviral expression vector, pLHY24, in
      which mhANP gene is under the transcriptional control of the human
      cytomegalovirus promoter, was constructed. The naked plasmid DNA of pLHY24 and
      positive control vector, pLHY19, in which the wild-type hNAP gene is in the same
      conditions as mhANP gene in pLHY24, and negative control vector, pLNCX without
      purpose gene, at a dose of 5 mg/kg body weight was injected intramuscularly into
      the rats with experimental renal disorder induced with adriamycin (ADR),
      respectively. RESULTS: DNA sequencing result proved that the respected mhANP gene
      with the point mutations of TTC(131)/Phe-->TCC/Ser and ATG(135)/Met-->ATA/Ile has
      been obtained. In comparison with negative control group (87 +/- 7.1 pg/ml), a
      single intramuscular injection of expression vector harboring mhANP or hANP gene
      resulted in an obvious increase in plasma level of mhANP (107 +/- 7.8 pg/ml, t =
      4.65, P < 0.01) or hANP (113 +/- 8.6 pg/ml, t = 5.71, P < 0.01) 5 days after
      injection. A significant elevation in the ratio of urine volume to body weight
      was occurred after both of mhANP gene and hANP gene delivery as compared with
      negative control and the effect lasted for more than 15 days. The diuretic
      activity of mhANP gene delivery was 1.6-, 2.0-, and 1.9-fold higher than that of
      hANP gene 5, 10, and 15 days after gene transfer, respectively. However, there
      were no statistical differences in the concentrations of K(+) and Na(+) in urine.
      CONCLUSIONS: Both of mhANP and hANP gene delivery into the rats with experimental
      nephropathy could improve their directic function obviously and the diuretic
      activity of the former is stronger than that of the latter significantly.

PMID- 12509937
TI  - [Advanced glycation end products inhibit production of nitric oxide by human
      endothelial cells through activation of the p38 signal pathway].
AB  - OBJECTIVE: To study the effect of advanced glycation end products (AGE) modified
      protein on nitric oxide (NO) production by human endothelial cells and the
      possible role of signal transduction pathway in this pathological procedure.
      METHODS: Human umbilical vein endothelial cells (HUVECs) and HUVEC-derived cell
      line (ECV304) were cultured in vitro with AGE modified human serum albumin (AGE
      HSA) or AGE modified bovine serum albumin (AGE-BSA) of the concentrations of
      12.5, 25, and 50 micro g/ml for 2, 4, 8, 12, and 24 hours. NO levels in the
      supernatant at each time point were determined by using Griess reagents. HUVECs
      and ECV304 cells incubated with HAS or BSA of the same concentrations were used
      as controls. The phosphorylation activity of cellular p38 mitogen-activated
      protein kinase (p38-MAPK) was analyzed by Western blot using a phospho-specific
      antibody after the cells were incubated with AGE-HAS or AGE-BSA of the
      concentration of 12.5, 25, 50, and 100 micro g/ml for 5, 15, 30, 60, and 120
      minutes. HUVECs were incubated with SB 203580, a specific inhibitor of p38, of
      the concentrations of 0.075, 0.15, and 0.3 micro mol/L for 4 hours, then the
      culture with SB 203580 was extracted. The endothelial cells were cleansed with
      RPMI 1640 culture and then were incubated with AGE-HAS or AGE-BSA for 8 hours.
      The No level in this supernatant was examined after the above-mentioned method.
      RESULTS: The NO level in the supernatant of culture of HUVECs incubated with AGE
      HAS or AGE-HAS for 2 hours were 92.2% +/- 10.1% and 94.1% +/- 12.5% of the
      controls respectively. The NO levels reached the lowest values, 72.4% +/- 7.14%
      and 68.3% +/- 10.9% of the values of the controls respectively after 8-hour
      incubation with AGE-HAS or AGE-HAS. AGE-HSA and AGE-BSA decreased the NO levels
      in the supernatant in a dose and time-dependant manner. The unmodified HSA and
      BSA did not influence the NO production by HUVECs or ECV304 cells. There was no
      difference in inhibition effect on NO production between AGE-HSA and AGE-BSA (P >
      0.05). There was no difference in response to AGE-HSA and AGE-BSA between HUVECs
      and ECV304 cells (P > 0.05). In the culture of HUVECs or of ECV304 cells
      incubated with AGE-HSA or AGE-BSA, the p38 phosphorylation activity was obviously
      enhanced 10 minutes after dose-dependently, reached its peak 30 minutes after,
      and returned to its basic level in 120 minutes. SB203580 of the concentration of
      0.3 micro mol/L completely abolished the inhibitive effect of AGE-albumin on NO
      production by endothelial cells. CONCLUSION: AGE modified protein inhibits the
      production of NO by human endothelial cells through activation of the p38 signal
      pathway. This AGE modification-induced pathobiological cascade may be involved in
      the pathogenesis of atherosclerosis seen in AGE-associated diseases.

PMID- 12509938
TI  - [Significance of p33(ING1b) and p53 gene expression in hepatocellular carcinoma].
AB  - OBJECTIVE: To explore the significance of p33(ING1b) protein expression and p53
      protein expression and investigate the mutation rate of ING1b gene in
      hepatocellular carcinoma (HCC). METHODS: Immunohistochemical method was employed
      to detect the expressions of p33(ING1b) and p53 proteins and the X antigen of
      hepatitis B virus (HBV) in 57 cases of HCC, 51 cases of surrounding non-tumor
      tissues surrounding HCC, and 12 cases of normal liver tissues; PCR-single strand
      conformation polymorphism (SSCP) was applied to reveal the mutation rates of two
      exons of ING1b gene in HCC. DNA fragments exhibiting abnormal shifting were
      cloned into PMD18-T vector and sequenced. RESULTS: The positive rates of
      p33(ING1b) protein and of p53 protein were 42.1% and 57.9% respectively among the
      57 cases of HCC. Both p33(ING1b) protein and p53 protein were positive in 19
      cases (33.3%) of HCC tissues, and they were distributed in the same areas, mostly
      in the nucleus. The expression of p33(ING1b) was significantly correlated with
      that of p53 protein (r = 0.783, P < 0.01). The matched surrounding non-tumor
      tissues and normal liver tissues all showed negative p53 staining, while weak
      positive expression of p33(ING1b) was observed in 13 cases out of the 51 non
      tumor tissues and 2 cases out of 12 normal liver tissues. Thirty-five cases, all
      with hepatocellular carcinoma, out of the 57 HCC cases showed positive HBV X
      protein (76.4%). The correlation of HBV infection with the expression of
      p33(ING1b) and p53 proteins was significant (P < 0.01). PCR-SSCP showed that the
      mutation rate of ING1b gene in HCC was 7.1% (2/28). CONCLUSION: The expression of
      p33(ING1b) protein is significantly related to the expression of p53 protein in
      hepatocellular carcinoma; The existence of p33(ING1b) may have some other p53
      independent pathway; Gene mutation was not the main reason that ING1b loses its
      tumor suppressing function in HCC. HBV infection has a close relationship with
      p33(ING1b) and p53 proteins expression.

PMID- 12509939
TI  - [Differentiation of rat bone marrow stromal cells into neuron induced by
      baicalin].
AB  - OBJECTIVE: To study the possibility that induced marrow stromal cells (MSCs) to
      neuron in vitro by baicalin, a kind of flavonoid isolated from an important
      medicinal plant Scutellariae Radix. METHODS: MSCs from adult SD rats were induced
      by baicalin in serum-free medium for 6 days. The expression of neuronal or glia
      specific markers and gene was evaluated by indirect immunofluorescence
      cytochemistry staining, Western blot, and reverse transcriptase-polymerase chain
      reaction (RT-PCR). The percentage of apoptotic cells at 6 days after baicalin
      treatment was measured by terminal deoxynucleotidyl transferase- mediated dUTP
      biotin nick end-labeling (TUNEL) assay. Moreover, differentiating cells that
      labeled by green fluorescent protein vector were transplanted to the striatum of
      adult SD rats after 6d of baicalin treatment. RESULTS: After induction for 6 d,
      MSCs displayed neuronal morphologies, such as pyramidal cell bodies and processes
      formed extensive networks. The undifferentiated cells did not exhibit a neuronal
      or glial phenotype. The differentiating cells expressed nestin, a marker of
      neural stem cells, at 6 h, and disappeared at 6 d. In contrast, expression of
      neuron-specific markers and gene was detectable at 6 d. And glia-specific markers
      and gene was not expressed. The percentage of apoptotic cells was 12.2% +/- 2.8%.
      In addition, fluorescently labeled cells were readily detected in the brain
      section after 14d of transplantation. CONCLUSION: Baicalin may induce adult rat
      MSCs to neuron in vitro. It is a useful vehicles for autotransplantation in both
      cell and gene therapy for a variety of diseases of the central nervous system.

PMID- 12509940
TI  - [Inhibition of tumor growth by a peptide fusion protein binding to vascular
      endothelial growth factor receptor Flt-1].
AB  - OBJECTIVE: Investigating the bio-activities of peptides selected from phage
      display peptide library with vascular endothelial growth factor receptor Flt-1.
      METHODS: Activities of DHFR-F56/F90 binding to human ubilial vein endothelial
      cells were detected by immunocytochemistry, and the activity of antiangiogenesis
      was determined with chick embryo chorioallantoric membrane (CAM) assay. Balb/c
      nude mice were used as model to detect the activity of DHFR-F56/F90 on inhibiting
      tumor growth, and immunohistochemistry was employed to determine the localization
      of the DHFR-F56/F90 in tumor. RESULTS: DHFR-F56/F90 can bind to HUVEC, and DHFR
      F56 inhibite angiogenesis in CAM. Meanwhile DHFR-F56 can bind with tumor cells,
      induce tumor necrosis and inhibit tumor growth in vivo. CONCLUSION: The peptide
      F56 is an effective antagonist of VEGF binding to Flt-1 and has a potent utility
      in antiangiogenesis and inhibiting tumor growth.

PMID- 12509941
TI  - [Activating protein-1 complex regulates oxidized low density lipoprotein-induced
      overproduction of rat TGF-beta1 at transcriptional level].
AB  - OBJECTIVE: To clarify whether the activating protein-1 (AP-1) is involved in the
      transcriptional regulation of expression of oxidized low density lipoprotein (Ox
      LDL) induced transforming growth factor (TGF)-beta(1) gene and further to
      investigate the possible signal transduction pathway in the cultured mesangial
      cells (MsCs). METHODS: Firstly, a deletion analysis of SD rat renal mesangial TGF
      beta(1) promoter (pRT)--luciferase reporter genes was adopted to identify the
      possible regulatory regions responding to Ox-LDL. With mutation of AP-1 binding
      site and addition of the c-Jun/AP-1 inhibitor curcumin, the changes of relative
      luciferase of pRT stimulated by Ox-LDL were assayed, respectively. Furthermore,
      the phosphorylation of p38MAPK was detected by Western blotting. Pre-treatment
      with the different specific kinase inhibitors, the activities of AP-1 induced by
      Ox-LDL were determined by electrophoretic mobility shift assay (EMSA). RESULTS:
      Relative luciferase activity showed two regions responding to stimulation by Ox
      LDL in rat TGF-beta(1) promoter: one positive regulatory region (-1 550 to -845)
      containing an accurate AP-1 binding site, and one negative (-629 to -422)
      regulatory region. Both mutation of AP-1 binding site and addition of curcumin
      markedly decrease of activity of TGF-beta(1) promoter. The phosphorylation, but
      not total protein, of p38MAPK was significantly enhanced by Ox-LDL stimulation.
      The inhibitor of PKC remarkably reduced the activity of AP-1 induced by Ox-LDL.
      Reversely, the activity of AP-1 didn't significantly change with the inhibitor of
      p38MAPK. CONCLUSION: In the cultured rat mesangial cells, the AP-1 complex
      regulates Ox-LDL induced-overproduction of TGF-beta(1) at the transcriptional
      level. Furthermore, the functional and structural results showed that Ox-LDL
      regulates rat TGF-beta(1) gene expression through AP-1 binding site and c-Jun/AP
      1 complex, it gives rise to the involvement of protein kinase C, but not p38MAPK,
      in Ox-LDL-induced TGF-beta(1) gene expression.

PMID- 12509942
TI  - [Anti-inflammatory effect of peroxisome proliferator-activated receptor-gamma
      incultured human mesangial cells].
AB  - OBJECTIVE: To investigate whether peroxisome proliferator-activator receptor
      gamma (PPARgamma) could retard the inflammatory challenge from human mesangial
      cells. METHODS: Based on the inflammatory mesangial cell model followed by IL
      1beta, the levels of IL-6 and TNF-gamma in the supernatants were measured by
      enzyme-linked immunosorbant assay (ELISA). PPARgamma protein expression of human
      mesangial cell lines (HMCL) lysate was detected with Western blot. PPARgamma, IL
      6 and TNF-gamma mRNA expression in HMCL lysate were measured by semi-quantitative
      RT-PCR assay. RESULTS: The levels of IL-6 and TNF-gamma in HMCL supernatants were
      dramatically increased when cultured HMCL were stimulated by IL-1beta (10 ng/ml).
      Protein and mRNA expressions of PPARgamma in IL-1beta challenge cells were
      significantly increased than observed in untreated cells. However, PPARgamma
      agonist troglitazone down-regulated mRNA and protein expression of PPARgamma from
      IL-1beta challenge HMCLs. PPARgamma agonists troglitazone, rosiglitazone, and 15
      deoxy-Delta(12, 14)-prosglandin J(2) significantly decreased the upexpression of
      TNF-alpha and IL-6 in HMCL supernatants stimulated by IL-1beta. Furthermore,
      troglitazone down-regulated TNF-alpha and IL-6 mRNA expression levels of HMCLs.
      CONCLUSION: These data suggest that PPARgamma play an important role in response
      to inflammatory stress in mesangial cells. PPARgamma may prove to be a
      pharmacological target in glomerulonephritis.

PMID- 12509943
TI  - [The expression of AmpC and extended-spectrum beta-lactamases among clinical
      isolates of enterobacter cloacae and its impact on antibiotics susceptibility].
AB  - OBJECTIVE: To investigate the expression of AmpC beta-lactamases and ESBL among
      clinical isolates of E. cloacae and its impact on antibiotic susceptibility.
      METHODS: Antibiotic susceptibility was determined by standard agar dilution
      procedures. beta-lactamases of the isolates with decreased susceptibilities to
      ceftazidime, cefotaxime, ceftriaxon or aztreonam were investigated by three
      dimensional extract tests, isoelectric focusing overlay technique, conjugation
      experiments and PCR. RESULTS: Among 106 E. cloacae isolates, 16.0% produced only
      high-level AmpC beta-lactamases, 10.4% produced only ESBL, 13.2% produced both
      high-level AmpC beta-lactamases and ESBL. 18 isolates (17.0%) carried CTX-M-type
      ESBL and 7 isolates (6.6%) carried SHV-type ESBL. All carbapenems showed high
      activity against E. cloacae strains (MIC90 <or= 2 micro g/ml). More than 70% of
      the isolates producing only high-level AmpC beta-lactamases were susceptible to
      cefepime, amikacin, gentamicin or ciprofloxacin. More than 60% of the isolates
      producing only ESBL were susceptible to piperacillin/tazobactam,
      cefoperazone/sulbactam, ciprofloxacin or amikacin. The susceptible rates of the
      isolates producing both high-level AmpC beta-lactamases and ESBL to tested
      antimicrobial agents other than carbapenems were all lower than 25%. CONCLUSION:
      CTX-M-type ESBL was prevalent among clinical isolates of E. cloacae. Resistance
      to expanded-spectrum cephalosporins in E. cloacae was mediated not only by AmpC
      beta-lactamases but also by ESBL. Expression of ESBL in high-level AmpC beta
      lactamases producing strains resulted in a significant rise in resistance level.

PMID- 12509944
TI  - What's new in the treatment of advanced prostate cancer?
AB  - Increased insight into the biology of prostate cancer and the emergence of new
      therapeutic strategies and chemotherapeutic agents has changed approaches in
      treating patients with advanced prostate cancer. After secondary hormonal
      manipulations, new approaches include: second-line hormonal therapy,
      chemotherapy, immunotherapy with granulocyte macrophage-colony stimulating factor
      (GM-CSF) therapy, dendritic cell therapy, gene vaccination therapy, inhibition
      and/or blockade of growth factor receptors or growth factor receptor pathways,
      inhibition of neo-angiogenesis and inhibition of invasion and metastases.

PMID- 12509945
TI  - New directions in testicular cancer; molecular determinants of oncogenesis and
      treatment success.
AB  - Metastatic testicular cancer is highly curable with conventional cytotoxic drugs.
      This is in contrast to most other metastatic solid tumours which can only be
      palliated with chemotherapy achieving only a modest impact on overall survival.
      If we could understand at the molecular level why chemotherapy is so effective in
      the treatment of testicular cancer, we may be better able to move other forms of
      metastatic cancer into the curable bracket. Most cytotoxic drugs appear to induce
      cell death by activating intracellular apoptotic mechanisms. Thus, the ability of
      a cancer to activate and execute such mechanisms in response to treatment is
      paramount in determining the effectiveness of chemotherapy. The basic study of
      cancer molecular biology is providing some insight into the proteins involved in
      this process and the ability to apply this information to actual human tumours is
      essential to rationalise clinical treatment failures at a molecular level.
      Testicular cancer provides an excellent model system in this analysis. Whereas
      there are large numbers of patients that are cured by chemotherapy, there are
      some whose cancers become resistant to treatment. An understanding of testicular
      cancer molecular biology may allow the identification of the genes regulating
      such a crucial behavioural switch. It may then be possible to manipulate specific
      signalling pathways to overcome drug resistance. This review focuses on recent
      developments in our understanding of the molecular biology of testicular cancer.
      A number of key players have been implicated including p53, pRb, cyclin D2, p INK
      proteins, c-kit and the bcl-2 family of proteins. The exact manner by which
      cellular transformation occurs has still not been established, but it is clear
      that many of the above proteins also have important roles in normal
      spermatogenesis. This is a developmental phase when the generation of genetic
      diversity is at a premium, but when selective apoptotic mechanisms are paramount.
      We discuss why this may be relevant to the behaviour of germ cell tumours and
      address possible reasons why they can become resistant to conventional therapy.

PMID- 12509946
TI  - Osteosarcoma over the age of forty.
AB  - The European Musculo Skeletal Oncology Society (EMSOS) has carried out a
      retrospective review of patients over the age of 40 years with osteosarcoma. 481
      patients from 12 centres or multicentric groups were included. 42 patients had
      osteosarcoma arising in Paget's disease, median survival was 9 months. Patients
      with axial or metastatic tumours also did badly whilst 41 patients with radiation
      induced osteosarcoma had a prognosis paralleling conventional osteosarcoma
      matched for patient age and site of the tumour. 238 patients had high grade non
      metastatic osteosarcoma and had a survival of 46% at 5 years. Older patients had
      less chemotherapy and fared worse. Osteosarcoma in the elderly is a curable
      condition and warrants intensive treatment with chemotherapy and surgical
      resection.

PMID- 12509947
TI  - Use of serum 5-S-CD and S-100B protein levels to monitor the clinical course of
      malignant melanoma.
AB  - 5-S-Cysteinyldopa (5-S-CD) is a precursor of pheomelanin. S-100B protein is a low
      molecular weight, acidic, calcium binding, cytoplasmic protein. In this study,
      the concentration changes of serum 5-S-CD and S-100B protein in melanomas of all
      stages were examined in parallel and patients were monitored during and after
      treatment. Serum samples were taken from 478 melanoma patients on 1924 occasions.
      Of these, 180 cases were regularly monitored. Concentrations of 5-S-CD were
      determined by high performance liquid chromatography (HPLC), S-100B protein by
      immunoluminometric assay. The mean/median concentrations of 5-S-CD and S-100B
      protein in Stage I, II and III patients and in the control group ranged around
      the normal level. In Stage IV patients, 58.4/50.6% sensitivity, 100% specificity
      and 100/86.6% positive predictive values were obtained concerning S-100B protein
      and 5-S-CD, respectively. Recurrence was observed in 57/180 of the regularly
      monitored patients in Stages I, II and III. In 10/57 (17.5%) of these patients
      suffering from any type of disease progression increases in both marker levels
      preceded the detection of metastasis by conventional methods. We can confirm that
      changes in both marker concentrations correlated with the stages of the patient.
      The markers are most sensitive in Stage IV patients and also have a high
      specificity in these patients. In Stage IV melanoma patients, 5-S-CD and S-100B
      protein levels are independent significant prognostic factors. In almost one
      fifth of patients both marker levels increased before the detection of metastatic
      disease with other appropriate, routinely scheduled investigations. This study
      suggests that serial serum marker measurements in the management and follow-up of
      melanoma patients should be examined further.

PMID- 12509948
TI  - Ultrasound-guided fine needle aspiration cytology of axillary lymph nodes in
      breast cancer patients. A preoperative staging procedure.
AB  - Currently, axillary lymph node dissection is increasingly being replaced by the
      sentinel node procedure. This method is time-consuming and the full
      immunohistochemical evaluation is usually only first known postoperatively. This
      study was designed to evaluate the accuracy of preoperative ultrasound-guided
      fine needle aspirations (FNAs) for the detection of non-palpable lymph node
      metastases in primary breast cancer patients. We evaluated the material of 183
      ultrasound-guided FNAs of non-palpable axillary lymph nodes of primary breast
      cancer patients. The cytological results were compared with the final
      histological diagnosis. Ultrasound-guided FNA detected metastases in 44% (37/85)
      of histologically node-positive patients, in 20% of the total patient population
      studied. These pecentages are likely to be higher when women with palpable nodes
      are included. Cytologically false-negative and false-positive nodes were seen in
      28 (15%) and three cases (1.6%), respectively. Interestingly 25% (n=7) of the
      false-negative nodes, revealed micrometastases on postoperative histology. The
      sensitivity was 57%, the specificity 96%. We conclude that ultrasound-guided FNA
      of the axillary lymph nodes is an effective procedure that should be included in
      the preoperative staging of all primary breast cancer patients. Whether lymph
      nodes are palpable or not, it will save considerable operating time by selecting
      those who need a complete axillary lymph node dissection at primary surgery and
      would save a significant number of sentinel lymph node dissections (SLNDs).

PMID- 12509949
TI  - Dynamic lymphoscintigraphy and image fusion of SPECT and pelvic CT-scans allow
      mapping of aberrant pelvic sentinel lymph nodes in malignant melanoma.
AB  - To date, there are no reliable criteria to identify those patients with melanoma
      infiltrated sentinel lymph nodes (SLNs) of the groin who might benefit from an
      extended lymphadenectomy, including the pelvic lymph nodes. We hypothesised that
      there are pelvic lymph nodes that receive lymph directly from the primary tumour,
      thus being at an increased risk for metastasis. In order to determine the
      frequency of radioactively labelled pelvic lymph nodes and the kinetics of their
      appearance, we introduce here a combination of dynamic lymphoscintigraphy, single
      photon emission computed tomography (SPECT) and image fusion of SPECT and pelvic
      Computed Tomography (CT)-scans. By dynamic lymphoscintigraphy and intraoperative
      gamma probe detection, superficially located inguinal SLNs (median 2 nodes) could
      be identified in all of the 51 patients included in this analysis. The
      histological search for micrometastases was positive in 16 patients (median
      Breslow thickness of the primary melanoma 2.5 mm). In 29 patients, SPECT and the
      image fusion technique were additionally performed. Radioactively labelled pelvic
      lymph nodes were detected in 20 individuals, 6 of them presenting aberrant pelvic
      SLNs that, on dynamic lymphoscintigraphy, had appeared simultaneously with the
      superficial SLN(s). Of the 6 patients in whom radioactive pelvic lymph nodes were
      excised together with the superficial SLN(s), only one had positive superficial
      SLNs. In this patient, the aberrant pelvic SLN proved to be tumour-positive. In 9
      patients, there was no radiotracer uptake in the pelvic lymph nodes at all. Image
      fusion of SPECT and pelvic CT-scans is an excellent tool to localise exactly the
      pelvic tumour-draining nodes. The significance of radioactively labelled pelvic
      lymph nodes for the probability of pelvic metastases should be analysed further.

PMID- 12509950
TI  - Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in
      patients with gastric cancer: possible role of a metastasis predictor.
AB  - The activation of coagulation, angiogenesis and inflammatory cytokines are
      considered to be related with tumour growth and metastasis. We investigated the
      plasma levels of platelet microparticles (PMP), vascular endothelial growth
      factor (VEGF), IL-6, and the chemokine RANTES in patients with gastric cancer
      (n=109) and in healthy controls (n=29). The plasma levels of PMP, IL-6 and RANTES
      were significantly higher in the patients than in the healthy controls, and
      plasma levels of PMP, VEGF, IL-6 and RANTES were significantly higher in patients
      with stage IV disease than those in patients with stage I or stage II/III. In
      terms of predicting distant metastasis, the sensitivities of PMP, VEGF, IL-6 and
      RANTES were 93.3%, 56.7%, 70.0% and 81.8%, respectively, and the corresponding
      specificities were 91.1%, 64.6%, 79.7% and 50.0%. Among these parameters, PMP had
      the highest diagnostic accuracy. Significant correlations were found between PMP,
      VEGF, IL-6 and RANTES. This study demonstrates that the plasma levels of PMP,
      VEGF, IL-6 and RANTES were markedly increased in patients with stage IV disease,
      and that these increased plasma levels of IL-6, RANTES, and especially PMP, might
      be useful for identifying metastatic gastric patients.

PMID- 12509951
TI  - A favourable pathological stage after neoadjuvant radiochemotherapy in patients
      with initially irresectable rectal cancer correlates with a favourable prognosis.
AB  - Initial treatments of locally advanced rectal cancers focus on local control, as
      local relapse of a rectal cancer is correlated with a high morbidity and
      mortality. We studied the effect of neoadjuvant radiochemotherapy on advanced
      rectal cancer patients in relation to downstaging, local relapse and survival.
      Post-treatment pathological staging, local relapse and survival were analysed in
      66 patients from a single institution. 43 patients had irresectable cancer as
      determined by laparatomy (n=42) or rectal examination (n=1). These 43 patients
      received 45-56 Gy preoperatively with 5-fluorouracil (5-FU) and leucovorin
      (350/20 mg/m(2)x5 day (d)) in weeks 1 and 5 during the radiation therapy. 23
      patients had primary resectable tumours with a T1-2 stage. Of the initially
      irresectable tumours 79% became macroscopically resectable, in 74% a R0 resection
      was performed. In 6 of 34 (18%) surgical specimens, no tumour was found (pT0), 7
      patients had small tumour remnants (pT1-2). In these pT0-2 tumours, no local
      relapses occurred (observation period of median 4.5 years, range 18-87 months).
      In the 21 patients with pT3-4 tumours 3 local relapses were seen. In the 23
      patients with primary resectable T1-2 tumours the relapse rate was 4%.
      Downstaging of an initially irresectable rectal tumour to pT2 or less results in
      a local relapse rate and overall survival that correspond with the rates in
      primary resectable cancer with the same T classification.

PMID- 12509952
TI  - Altered clearance of unbound paclitaxel in elderly patients with metastatic
      breast cancer.
AB  - The pharmacokinetic behaviour of anticancer drugs may be altered with aging due
      to (for example) differences in body composition and decreased hepatic and renal
      function. To address this issue for paclitaxel, we studied the pharmacokinetics
      of the drug in eight elderly women (>or=70 years) with metastatic breast cancer
      (median age (range), 77 years (70-84 years)) and a control group of 15 patients
      aged <70 years (median age (range), 54 years (22-69 years)). Paclitaxel was
      administered as a 1-h intravenous (i.v.) infusion at a dose of 80 (elderly) or
      100 mg/m(2) (<70 years), and serial blood samples were obtained at baseline, and
      up to 24 h after the end of infusion. Paclitaxel concentration-time profiles were
      fitted to a linear three-compartment model without any demonstration of saturable
      behaviour. The clearance of unbound paclitaxel was 124+/-35.0 (elderly) versus
      247+/-55.4 l/h/m(2) (<70 years) (P=0.002), and was inversely related to the
      patient's age (R(2)=0.857; P<0.00001). Total plasma clearance of the formulation
      vehicle Cremophor EL (CrEL) was 150+/-60.7 (elderly) versus 115+/-39.2 ml/h/m(2)
      (<70 years) (P=0.04). These data indicate an approximately 50% change in total
      body clearance of unbound paclitaxel and a concomitant significant increase in
      systemic exposure with age, most likely as a result of altered CrEL disposition.
      The clinical relevance of these observations with respect to toxicity profiles
      and antitumour efficacy requires further evaluation.

PMID- 12509953
TI  - No excess fatigue in young adult survivors of childhood cancer.
AB  - Clinical reports suggest that many survivors of childhood cancer experience
      fatigue as a long-term effect of their treatment. To investigate this issue
      further, we assessed the level of fatigue in young adult survivors of childhood
      cancer. We compared the results with a group of young adults with no history of
      cancer. The impact of demographic, medical and treatment factors and depressive
      symptoms on survivors' fatigue was studied. Participants were 416 long-term
      survivors of childhood cancer (age range 16-49 years, 48% of whom were female)
      who had completed treatment an average of 15 years previously and 1026 persons
      (age range 16-53 years, 55% female) with no history of cancer. All participants
      completed the Multidimensional Fatigue Inventory (MFI-20), a self-report
      instrument consisting of five scales (general fatigue, physical fatigue, mental
      fatigue, reduced activity, reduced motivation) and the Center for Epidemiologic
      Studies Depression Scale (CES-D). Small differences were found in the mean scores
      for the different dimensions of fatigue between the long-term survivors and
      controls (range effect sizes -0.34 to 0.34). Women experienced more fatigue than
      men. Logistic regression revealed that being female and unemployed were the only
      demographic characteristics explaining the various dimensions of fatigue. With
      regard to medical and treatment factors, diagnosis and severe late effects/health
      problems were associated with fatigue. Finally, depression was significantly
      associated with fatigue on all subscales. Our clinical practice suggests a
      difference in fatigue in young adult childhood cancer survivors and their peers.
      This could not be confirmed in this study using the MFI-20. The well known
      correlation between fatigue and depression was confirmed in our study. Further
      research is needed to clarify the undoubtedly complex somatic and psychological
      mechanisms responsible for the development, maintenance and treatment of fatigue
      in childhood cancer survivors.

PMID- 12509954
TI  - Long-term survival of women with breast cancer in New South Wales.
AB  - Several long-term studies of breast cancer survival have shown continued excess
      mortality from breast cancer up to 20-40 years following treatment. The purpose
      of this report was to investigate temporal trends in long-term survival from
      breast cancer in all New South Wales (NSW) women. Breast cancer cases incident in
      1972-1996 (54,228) were derived from the NSW Central Cancer Registry-a population
      based registry which began in 1972. All cases of breast cancer not known to be
      dead were matched against death records. The expected survival for NSW women was
      derived from published annual life tables. Relative survival analysis compared
      the survival of cancer cases with the age, sex and period matched mortality of
      the total population. Cases were considered alive at the end of 1996, except when
      known to be dead. Proportional hazards regression was employed to model survival
      on age, period and degree of spread at diagnosis. Survival at 5, 10, 15, 20 and
      25 years of follow-up was 76 per cent, 65 per cent, 60 per cent, 57 per cent and
      56 per cent. The annual hazard rate for excess mortality was 4.3 per cent in year
      1, maximal at 6.5 per cent in year 3, declining to 4.7 per cent in year 5, 2.7
      per cent in year 10, 1.4 per cent in year 15, 1.0 per cent for years 16-20, and
      0.4 per cent for years 20-25 of follow-up. Relative survival was highest in 40-49
      year-olds. Cases diagnosed most recently (1992-1996) had the highest survival,
      compared with cases diagnosed in previous periods. Five-year survival improved
      over time, especially from the late 1980s for women in the screening age group
      (50-69 years). Survival was highest for those with localised cancer at diagnosis:
      88.4 per cent, 79.1 per cent, 74.6 per cent, 72.7 per cent and 72.8 per cent at
      5, 10, 15, 20 and 25 years follow-up (excluding those aged >or=70 years). There
      was no significant difference between the survival of the breast cancer cases and
      the general population at 20-25 years follow-up. Degree of spread was less
      predictive of survival 5-20 years after diagnosis, compared with 0-5 years after
      diagnosis, and was not significant at 20-25 years of follow-up. Relative survival
      from breast cancer in NSW women continues to decrease to 25 years after
      diagnosis, but there is little excess mortality after 15 years follow-up,
      especially for those with localised cancer at diagnosis, and the minimal excess
      mortality at 20-25 years of follow-up is not statistically significant.

PMID- 12509955
TI  - Skin cancer and non-Hodgkin's lymphoma as second malignancies. markers of
      impaired immune function?
AB  - Successes in cancer therapy have led to increasing numbers of cancer survivors,
      who are at risk of developing second primary cancers. Therapy- or disease-induced
      suppression of the immune function may predispose cancer patients to a second
      malignancy. An excess of squamous cell skin cancers (SCC) and non-Hodgkin's
      lymphomas has been found in immunosuppressed patients. We used the nationwide
      Swedish Family-Cancer Database on 10.2 million individuals to calculate the risk
      of second primary skin cancers and non-Hodgkin's lymphomas following a previous
      malignancy. A total of 4301 second skin cancers and 1672 non-Hodgkin's lymphomas
      were identified. Standardised incidence ratios (SIR)s and 95% Confidence
      Intervals (CIs) were calculated and compared. Among 14 different sites for male
      or female first primary malignancies, 11 of these sites were followed by an
      increased risk of skin cancer (SIRs for males for risk of skin cancer as a second
      primary cancer: 14.1 for SCC; 9.7 for melanoma; 6.1 for leukaemia as the first
      site; SIRs for females for risk of skin cancer: 14.6 for SCC; 6.8 for larynx; 6.2
      for upper aerodigestive tract (UADT) as the first site). The risk of non
      Hodgkin's lymphoma was increased after 10 of 14 different male neoplasms and 12
      of 17 different female neoplasms. (SIRs for males for risk of non-Hodgkin's
      lymphoma as a second primary cancer: 6.4 for non-Hodgkin's lymphoma; 3.2 for
      leukaemias; 3.1 for multiple myeloma as the first site; SIRs for females for risk
      of non-Hodgkin's lymphoma as a second primary cancer: 12.5 for leukaemias; 7.0
      for Hodgkin's disease; 3.6 for UADT as the first site). The high, and after
      certain sites, very high risks of second skin cancer and non-Hodgkin's lymphoma
      suggest that immune suppression may be a contributory mechanism.

PMID- 12509956
TI  - Chemopreventive agents induce a senescence-like phenotype in rat mammary tumours.
AB  - Terminal replicative senescence (TRS) is a physiological process associated with
      terminal differentiation, shortening of the telomere, and lack of proliferative
      activity. Immortalised and tumour cells have lost their differentiation potential
      and the ability to develop a senescence phenotype. Recently, others and we [11]
      have observed that some antitumour agents and radiation induce a senescence-like
      phenotype (SLP) in human immortalized and tumour cell lines. The main purpose of
      this study was to identify senescence-like cells (SLC) in mammary tumours of rats
      and assess whether chemopreventive agents that have been used for the prevention
      and/or treatment of breast cancer can induce a SLP in tumour cells. Sprague
      Dawley rats with N-methyl-N-nitrosourea (MNU)-induced mammary tumours were
      randomised and treated with tamoxifen, vorozole, 4-(hydroxyphenyl)retinamide (4
      HPR), or 9-cis-retinoic acid (9cRA). The SLC in mammary tumours were identified
      and characterised by: (a) SA-beta-Gal staining method, which has been considered
      specific for human cells in TRS (b) staining for lipofuscin, which, although not
      specific, accumulates in the cytoplasm of cells in senescence; (c) lack of 5
      Bromodeoxyuridine (BrdU) labelling after continuous (7 days) infusion of BrdU via
      osmotic pumps; (d) 90 degrees side light scatter (9OLS) as evaluated by flow
      cytometry; and (e) decreased telomerase activity. We found that in control
      tumours, SA-beta-Gal-positive cells were rare (below 1.0%) among the tumour
      cells, stroma fibroblast, myoepithelial and endothelial cells. SA-beta-Gal
      positive cells increased significantly in the tumours treated with
      chemopreventive agents and this was associated with a lack of proliferative
      activity, increased cell granularity, lipofuscin accumulation, and decreased
      telomerase activity. Thus, in this study we provide for the first time evidence
      that cells in replicative senescence are present in mammary tumours of rats and
      that chemopreventive agents can suppress tumor growth by a novel cellular
      mechanism, inducing a SLP in the tumor cells.

PMID- 12509957
TI  - Defective mismatch-repair in patients with multiple primary tumours including
      colorectal cancer.
AB  - Individuals with an inherited predisposition to cancer development are at an
      increased risk of developing multiple tumours. Hereditary non-polyposis
      colorectal cancer (HNPCC) is one of the most common hereditary cancer syndromes
      and is estimated to account for approximately 2% of colorectal cancers. However,
      HNPCC individuals are at an increased risk of developing other tumour types such
      as cancers of the endometrium, urothelium and small intestine. We have utilised a
      population-based regional cancer registry to identify all patients with double
      primary colorectal cancers and at least one additional malignancy and
      characterised the tumour spectrum in this patient group. We subsequently selected
      those 47 individuals who had developed at least four malignancies, including two
      colorectal cancers, for studies of the tumour characteristics associated with
      HNPCC. In total, these individuals developed 209 tumours, 156 of which were
      successfully retrieved. Microsatellite instability (MSI), a phenomenon caused by
      defective mismatch-repair (MMR), was identified in 63/154 (41%) evaluable tumours
      with a MSI-high pattern in 59 and a MSI-low pattern in four tumours. All tumours
      were immunohistochemically stained for the MMR proteins MLH1 and MSH2, with loss
      of expression in 55/63 (87%) MSI tumours and in 2/89 (2%) microsatellite stable
      (MSS) tumours. This loss affected MLH1 in 24 tumours and MSH2 in 33 tumours. A
      concordant loss of expression for the same MMR protein in several tumours from
      the same individual, a pattern that strongly suggests an underlying germline MMR
      gene mutation, was found in 17/45 (38%) patients and affected MLH1 in 8 patients
      and MSH2 in 9 patients. We conclude that the development of multiple primary
      tumours, including synchronous or metachronous colorectal cancers, is associated
      with an increased frequency of MSI and loss of immunohistochemical expression of
      MLH1 and MSH2.

PMID- 12509958
TI  - The death associated protein (DAP) kinase homologue Dlk/ZIP kinase induces p19ARF
      and p53-independent apoptosis.
AB  - Dlk/ZIP kinase is one of five members of the death associated protein (DAP)
      kinase family. DAP kinase is able to induce apoptosis in a p19ARF/p53-dependent
      manner. We elucidated the potential role of the p19ARF/p53 pathway in Dlk/ZIP
      kinase-triggered cell death. Overexpression of a constitutively pro-apoptotic
      form of Dlk/ZIP kinase induced apoptosis in rat fibroblast cells which express
      wild-type p19ARF and p53. Cell death was characterised by apoptotic membrane
      blebbing, mitochondrial depolarisation, cytochrome c release and activation of
      caspase-3. However, Dlk/ZIP kinase-triggered cell death was also observed in
      p19ARF-deficient and p53-deficient mouse fibroblast cells. Quantitative analysis
      revealed that the status of p53 had no major influence on cellular susceptibility
      to Dlk/ZIP kinase-triggered cell death. Loss of p53 did not prevent Dlk/ZIP
      kinase-induced mitochondrial membrane depolarisation and release of cytochrome c.
      Furthermore, overexpression of Dlk/ZIP kinase did not lead to an increased
      expression of pro-apoptotic p53 target genes in either cell line. These data
      suggest that Dlk/ZIP kinase is able to trigger the mitochondrial apoptosis
      pathway independent of the p19ARF/p53 signalling pathway.

PMID- 12509959
TI  - In vivo expression of the whole HOX gene network in human breast cancer.
AB  - The HOX network contains 39 genes that act as transcriptional regulators and
      control crucial cellular functions during both embryonic development and adult
      life. Inside the network, this is achieved according to the rules of temporal and
      spatial co-linearity with 3' HOX genes acting on the anterior part of the body,
      central HOX genes on the thoracic part and lumbo-sacral HOX genes on the caudal
      region. We analysed HOX gene expression in normal breast tissue and in primary
      breast cancers by reverse-transcriptase-polymerase chain reaction (RT-PCR). 17
      out of 39 HOX genes were expressed in the normal breast tissue. The expression of
      thoracic HOX genes tended to be similar in normal and neoplastic breast tissues
      suggesting that these genes are involved in breast organogenesis. In contrast,
      cervical and lumbo-sacral HOX gene expression was altered in the primary breast
      cancers with respect to normal breast tissue. This supports their involvement in
      breast cancer evolution and suggests they could be targets for future cancer
      therapies.

PMID- 12509960
TI  - Second primary cancers in laryngeal cancer patients.

PMID- 12509961
TI  - Risk factors for ulcerative oral mucositis in cancer patients: unanswered
      questions.
AB  - A multitude of laboratory and clinical research studies of ulcerative oral
      mucositis induced by cytotoxic cancer therapies have been reported during the
      past decade. However, a comprehensive understanding of oral mucositis
      pathogenesis, together with a clear definition of risk factors for development
      and severity of the lesion, remain under investigation. The literature presents
      sometimes divergent data regarding these issues, which in turn restrict efforts
      to develop a unified approach for management of this morbid condition. The
      current review summarizes these controversies and highlights the need for
      strategies for stratification of patients enrolled in clinical trials, in
      relation to both pathophysiologic and associated risk factors.

PMID- 12509962
TI  - Current philosophy on the management of cancer of the base of the tongue.
AB  - Cancer of the base of the tongue is a challenging disease for the head and neck
      surgeon, radiation oncologist and medical oncologist. However, over the last 10
      15 years, improved treatment strategies have evolved which offer patients high
      probability of loco-regional control, survival, and good quality of life. The
      ability to offer patients good oncologic and functional outcomes serves as a
      paradigm for the successful application of multidisciplinary care, and the
      emphasis on quality of life in head and neck cancer treatment. This review
      provides an overview of the treatment options that exist, their advantages and
      disadvantages, and hopefully provides proper guidelines for the current
      management of this challenging disease.

PMID- 12509963
TI  - Squamous cell carcinoma of the oral cavity in patients aged 45 years and under: a
      descriptive analysis of 116 cases diagnosed in the South East of England from
      1990 to 1997.
AB  - BACKGROUND: there is, currently, much anecdotal and some epidemiological evidence
      for a rise in oral cancer rates amongst younger individuals, many of whom have
      had no exposure to traditional risk factors such as tobacco and heavy alcohol
      use, or at least not the exposure over decades usually associated with this
      disease. The probity of this assertion and the presence or absence of traditional
      risk factors needs further evidence. OBJECTIVES: this paper describes the
      demography and the exposure to potential risk factors amongst a cohort aged 45
      years and younger, diagnosed with squamous cell carcinoma of the oral cavity
      between 1990 and 1997 from the South East of England. MATERIALS AND METHODS:
      eligible patients registered with a cancer registry were included in this
      retrospective study. Information was accessed from the database and by a postal
      questionnaire survey. The self-completed questionnaire contained items about
      exposure to the following risk factors: tobacco; alcohol; diet; frequency of
      dental visits and familial cancer. RESULTS AND CONCLUSIONS: this is the largest
      UK epidemiological study so far to be undertaken on young subjects diagnosed with
      oral cancer. One-hundred and sixteen cases were recruited representing a response
      rate of 59%. Slightly over 90% of this cohort were classified as white European.
      A large proportion of cases (40%) were from social classes I & II suggesting
      either a true social class difference in young cases versus older oral cancer
      cases or a possible bias in responders or survivors. Risk factors of tobacco use
      and excessive alcohol consumption were present in the majority (75%) of patients.
      Significant differences in the pattern of alcohol consumption were found in
      female subjects, who were less likely to consume over the recommended amounts of
      alcohol compared with male subjects. Daily regular fresh fruit and vegetable
      consumption during the ten year period before cancer diagnosis was recorded to be
      low. There was a distinct subgroup of cases, 26% of the group, that showed
      little, if any, exposure to any major risk factors.

PMID- 12509964
TI  - Allelic imbalance at the DNA mismatch repair loci, hMSH2, hMLH1, hPMS1, hPMS2 and
      hMSH3, in squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the 10
      most frequently occurring cancers in the world. Defective mismatch repair, as
      exhibited by the phenomenon of microsatellite instability, has been observed in
      SCCHN although no reports of mismatch repair gene mutations or altered protein
      expression have been published. In a variety of microsatellite instability (MSI)
      positive cancers where mutations in the mismatch repair (MMR) genes were not
      observed, allelic imbalance at the loci of the MMR genes was prevalent.
      OBJECTIVE: To investigate whether allelic imbalance at the MMR genetic loci
      contributes to the development of SCCHN. MATERIALS AND METHODS: 35 matched
      normal/tumour SCCHN pairs were studied using 29 microsatellite markers located
      within and adjacent to six known DNA mismatch repair genes. In addition,
      mutational analysis and protein expression of hMSH2 and hMLH1 were investigated.
      RESULTS AND CONCLUSIONS: We demonstrated that 36 and 17% of the analysed SCCHN
      specimens exhibited allele imbalance at the hMLH1 and hMSH3 genetic loci,
      respectively. Allelic instability at these two loci was found to be correlated
      with the MSI status of the SCCHN tumours. Allelic instability was found to be
      uncommon at the other MMR gene loci analysed. One mutation was found in hMSH2 and
      none in hMLH1 in this series of tumours. 23 of 24 (96%) of the examined SCCHN
      tumours showed reduced expression of either hMSH2 or hMCH1 genes. Allelic
      instability in the MMR genes, hMLH1 and hMSH3, is proposed to be involved in the
      aetiology of SCCHN tumours.

PMID- 12509965
TI  - Cervical lymph node metastasis in oral cancer: the importance of even microscopic
      extracapsular spread.
AB  - The prognostic significance of extracapsular spread of cervical metastases in
      oral cancer is still controversial. To investigate the importance of extent of
      extracapsular spread; the relationship between extracapsular spread and both
      traditional measures of metastatic disease and clinical/histological features of
      the primary tumour, and to determine their relative prognostic significance. The
      survival of 173 patients undergoing radical surgery and simultaneous neck
      dissection for oral/oropharyngeal squamous cell carcinoma with histologically
      confirmed nodal metastasis and followed for 2.2-12.3 years is reported and
      related to pathological features. The most predictive clinical/histopathological
      features were determined by Cox regression modelling. The 3-year survival
      probability was similar for patients with macroscopic and only microscopic
      extracapsular spread (33 and 36%, respectively, compared with 72% for patients
      with intranodal metastasis). The Cox model showed the most predictive factor was
      extracapsular spread followed by status of resection margins. Extracapsular
      spread should be incorporated into pathological staging systems. Even microscopic
      extracapsular spread is of critical importance and must be sought especially in
      small-volume metastatic disease.

PMID- 12509966
TI  - Epidermal growth factor receptor expression in ameloblastoma.
AB  - Ameloblastoma is a locally aggressive tumor with possible lethal potential.
      Currently extensive surgery is the most acceptable treatment modality. AIM: To
      investigate the presence of EGFR in ameloblastoma in order to consider using
      newly developed anti-EGFR therapeutic agents in cases of unresectable tumors. The
      study consisted of 58 formalin-fixed, paraffin-embedded specimens of
      ameloblastoma that were immunohistochemically stained with a monoclonal anti-EGFR
      antibody (clone 31G7). Positive and negative controls determined specificity of
      the antibody. A staining score based on the staining intensity and the proportion
      of stained cells was established, ranging between 0 and 2. All specimens were
      EGFR positive; 8 (14%) exhibited the maximum score of 2 and 19 (33%) scored
      between 1 and 2. Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents
      could be considered to reduce the size of large tumors and to treat unresectable
      tumors that are in close proximity to vital structures.

PMID- 12509967
TI  - Concurrent chemoradiotherapy with new platinum compound nedaplatin in oral
      cancer.
AB  - Eleven patients with oral cancer were treated with the new platinum agent,
      nedaplatin, and 5-fluorouracil and simultaneous radiation therapy. The regimen
      was of 5 days' duration: 5-fluorouracil 400-500 mg/m(2) (days 1-5), nedaplatin 80
      90 mg/m(2) (day 4), and a total radiation dose of 8-10 Gy (days 1-5). Of the 11
      patients, 4 (36.4%) showed complete response and 5 (45.4%) showed partial
      response; the total response rate was 81.8%. Major side effects were hypochromia
      (27%), leukopenia (64%), granulocytopenia (55%), thrombocytopenia (36%), nausea
      and vomiting (82%), and mucositis (45%). Toxicity was grade 2 or less in most of
      the 11 patients. The results indicate that the regimen composed of combination
      chemotherapy with nedaplatin and radiation therapy is effective in the treatment
      of patients with squamous cell carcinoma of the oral region.

PMID- 12509968
TI  - Characterization of autofluorescence in oral squamous cell carcinoma.
AB  - This study was carried out to evaluate the clinical characteristics of
      autofluorescence in oral squamous cell carcinoma (SCC) and analyze the
      fluorescent substances using high-performance liquid chromatography (HPLC). Fifty
      of 55 oral SCCs (91%) emitted orange or red fluorescence, which was recorded by
      fluorescence photography. The intensity of the fluorescence significantly
      correlated with the T and N categories of the cancers, but did not show
      statistical difference for the types of clinical appearance and primary sites.
      Protoporphyrin and coproporphyrin were identified as the fluorescent substance in
      the SCC samples, and the elution patterns on HPLC revealed some porphyrin
      compounds as specific to oral cancer. These results suggest that the
      autofluorescence in oral SCC correlates with the progression of lesions, and that
      fluorescent substances such as protoporphyrin are produced in association with
      the cancerous tissue.

PMID- 12509969
TI  - Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a
      chemoresistance marker in human oral squamous cell carcinoma treated with
      cisplatin.
AB  - An important clinical problem in the treatment of oral squamous cell carcinoma is
      the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper
      transporting P-type adenosine triphosphate (ATP7B) has been reported to be
      associated with cisplatin resistance in vitro (Komatsu et al., Cancer Res 60,
      1312-1316,2000). However, the clinical significance of this transporter has not
      previously been addressed. Our aim of this study was to investigate if ATP7B is
      expressed in oral squamous cell carcinoma and whether its expression correlates
      with prognosis and reduced responsiveness to cisplatin treatment. Biopsy tissues
      were obtained from the tumors of 70 patients with oral SCC, and 51 patients
      received cisplatin-based preoperative chemotherapy. We performed
      immunohistochemical analysis of ATP7B using monoclonal antibody against ATP7B in
      51 oral SCC and adjacent neoplastic tissues. The significance of ATP7B in the
      prognosis of patients with oral SCC was also examined in the survival analysis of
      mortality follow-up data covering the period 1991 through 2000. We
      retrospectively examined the expression of ATP7B in primary oral SCC carcinoma
      and its association with chemotherapeutic effect. A variable degree of
      cytoplasmic staining of tumor cells was observed in 54.9% (28/51 cases) of the
      analyzed carcinomas. Patients with ATP7B-positive tumors had a significantly
      inferior response to chemotherapy compared with the patients with ATP7B-negative
      tumors (P = 0.03). The patients who received cisplatin-based chemotherapy with
      ATP7B-positive carcinomas had a significantly poorer overall survival than those
      with ATP7B-negative tumors (P = 0.015). These findings suggest that high levels
      of ATP7B expression in oral SCC are associated with unfavorable clinical outcome
      in patients with oral SCCs treated with cisplatin-based chemotherapy. ATP7B
      expression may be a preoperative indicator for a choice of cisplatin in some
      patients.

PMID- 12509970
TI  - Specific p53 mutations predict poor prognosis in oral squamous cell carcinoma.
AB  - In this study, we focused on p53 mutations in specific regions, including DNA
      binding surface regions, to clarify the correlation between mutations within the
      specific regions of p53 and clinical outcomes of patients with oral cancers. We
      analyzed p53 mutations in 121 fresh primary oral squamous cell carcinomas (SCCs)
      by polymerase chain reaction-single-strand conformation polymorphism or a yeast
      functional assay. p53 mutations were detected in 51/121 (42%) cases. Mutation of
      p53 was not associated with any clinicopathological parameters; however, tumors
      containing specific p53 mutations, e.g. DNA-binding surface regions (L2, L3 and
      the LSH motif) and conserved regions (II-V), had significantly poorer prognoses
      than tumors with mutations outside of those regions. Moreover, locoregional
      failure, lymph node metastasis and the occurrence of subsequent distant
      metastasis were also significantly associated with mutations within DNA-binding
      surface regions. These data indicate that specific mutations of p53 could be
      important prognostic factors in oral SCCs.

PMID- 12509971
TI  - Radiation response non-invasively imaged by [18F]FDG-PET predicts local tumor
      control and survival in advanced oral squamous cell carcinoma.
AB  - It is a major challenge to preoperatively identify patients who will profit from
      surgery of advanced oral cancer. In multimodality therapy, response to
      neoadjuvant radiation correlates to treatment success. Hence, for preoperative
      decisions, assessment of treatment response is required. Therefore, we analysed
      the prognostic significance of glucose metabolism after preoperative
      radiotherapy. [(18)F]FDG-PET investigations were performed for re-staging 35
      patients after neoadjuvant radiotherapy (36Gy) immediately prior to tumor
      resection. Emission and transmission measurements were obtained and SUV's were
      calculated for the sites of maximum [(18)F]FDG-uptake. Subpopulations of "low"
      (SUV < 4) and "high" (SUV > or = 4) glucose metabolism were compared by
      univariate and multivariate survival analysis. 3-years survival was 80% in the
      "low" SUV group and 43% in the "high" SUV group. Post-irradiation [(18)F]FDG
      uptake significantly predicts survival (P = 0.046) and local tumor control (P =
      0.0017). High [(18)F]FDG-uptake was associated with an increased hazard of death
      (P = 0.037) and especially of local progress (P = 0.011) even when radical
      resection was performed. Thus, [(18)F]FDG-PET non invasively identified patients
      with poor prognosis whose indication for radical surgery has to be considered
      with caution.

PMID- 12509972
TI  - Root surface areas in long-term survivors of childhood cancer.
AB  - Treatment regimes for childhood cancer are known to affect the root development
      in the long-term survivors (LTS) but the available the data is subjective in
      nature with very few quantitative data in the literature. This study aimed to
      quantify the root surface area (RSA) of mandibular teeth in LTS compared with
      controls and relate this to the treatment regime and also to the age at which the
      cancer was diagnosed. Panoramic radiographs were obtained from 69 LTS and an
      equal number of appropriately matched healthy controls. RSA were calculated using
      Computer Linked Image Analysis. RSA in the LTS were found to be significantly
      smaller as compared with controls. Also, RSA were the least in those LTS who had
      Total Body Irradiation followed by Bone Marrow Transplantation (TBI/BMT) compared
      with other treatment regimes, the difference being statistically significant for
      all teeth studied. There was no relationship between the RSA and the age at which
      the cancer was diagnosed. Smaller root areas have implications for the oral
      health of LTS, as bone loss around such teeth will compromise further their
      periodontal support thus jeopardising the long-term survival of the tooth.

PMID- 12509973
TI  - Hyperthermic photodynamic therapy combined with topical administration of OK-432
      in the mouse carcinoma.
AB  - This study investigated the combined effect of photodynamic therapy (PDT) using
      high power laser irradiation (HPL), which generates both a hyperthermic and a
      photodynamic effect, and OK-432 on NR-S1 mouse squamous cell carcinoma. The
      photosensitizer (haematoporphyrin oligomers 20 mg/kg BW) was injected to the mice
      intraperitoneally 48 h before laser irradiation. OK-432 was injected into the
      tumour 3 h prior to laser irradiation. The experimental protocols consisted of
      HPL-PDT with or without OK-432, low power laser PDT with or without OK-432, HPL
      alone and OK-432 alone, and a control group. The tumour necrotic area was
      determined, and tumour sizes were measured 3, 7 and 10 days after each protocol.
      The anti-tumour effect of HPL-PDT was enhanced by preadministration with OK-432.
      Treatment with OK-432 alone or hyperthermic HPL irradiation presented little anti
      tumour effect. HPL-PDT in combination with OK-432 topically administered 3 h
      before photo-irradiation is considered to be a promising therapeutic modality.

PMID- 12509974
TI  - Metastasising clear cell odontogenic carcinoma: a case report and review of the
      literature.
AB  - Primary odontogenic carcinomas are rare and examples which have metastasised are
      even more uncommon. We describe the first reported case of a clear cell
      odontogenic carcinoma which metastasised to distant bones, namely the 5th lumbar
      vertebra and hip, 3 years after initial diagnosis. The initial incisional biopsy
      was thought to represent a calcifying epithelial odontogenic tumour, but in the
      subsequent resection the tumour showed a prominent clear cell component admixed
      with squamous cells showing peripheral palisading, widespread infiltration and
      necrosis indicating a malignant neoplasm. Radiologically guided biopsy revealed a
      metastatic lesion in L5 vertebrae and left hip, confirmed by
      immunohistochemistry. The metastatic lesion had similar appearances to the first
      biopsy, and diagnosis was confirmed by comparison of histological features,
      immunohistochemistry and exclusion of a second primary lesion by clinical
      examination and imaging. The diagnosis of clear cell odontogenic carcinoma is a
      difficult one to make. The behaviour of these tumours is unpredictable. This case
      confirms that clear cell odontogenic carcinomas have the potential for distant
      metastasis and require long-term follow up.

PMID- 12509975
TI  - Microcystic adnexal carcinoma: an unusual cause of swelling and paraesthesia of
      the lower lip.
AB  - Microcystic adnexal carcinoma (MAC) is an uncommon, recently described, cutaneous
      adnexal malignant neoplasm, associated with significant morbidity as a
      consequence of its propensity for perineural invasion. The present report details
      the clinical and histological features of MAC in a young female presenting with
      lower labial swelling and paraesthesia.

PMID- 12509976
TI  - Oncocytic carcinoma arising in submandibular gland with immunohistochemical
      observations and review of the literature.
AB  - We report a case of oncocytic carcinoma arising in submandibular gland. The
      tumour occurred in the left submandibular gland of an 82-year-old Japanese man.
      Histologically, the tumour was mostly composed of large cells with eosinophilic
      granules in the cytoplasm and they were arranged in the solid sheets, islands
      with duct-like structure and cords. The tumour cells had aggressively invaded
      muscles and perineural tissues, and cervical lymphatic metastasis was frequently
      observed. Histochemically, the tumour cells were strongly positive for
      phosphotungstic acid-hematoxylin (PTAH) stain, and we diagnosed this malignant
      tumour as oncocytic carcinoma. Immunohistochemically, the tumour cells reacted
      positively for cytokeratin 7, 8, 19, epithelial membrane antigen (EMA), alpha-1
      antichymotrypsin and carcinoembryonic antigen (CEA), but negative for cytokeratin
      13, 14, smooth muscle actin (HHF35) and S-100 protein (S-100). Tumour was
      diagnosed as oncocytic carcinoma in submandibular gland. Its characteristics are
      discussed in term of its histopathological and immunohistochemical features.

PMID- 12509977
TI  - Many faces of odontogenic keratocyst.

PMID- 12509978
TI  - Expression and purification of biologically active IGF-binding proteins using the
      LCR/Mel expression system.
AB  - The anabolic effects and bioavailability of insulin-like growth factors I and II
      (IGF-I, IGF-II) are regulated in part by a family of IGF-binding proteins
      (IGFBPs). There are six known members of the IGFBP family, which share distinct
      structural characteristics and functional activities. To study the binding
      properties of these proteins, we have expressed recombinant IGFBP-3 and IGFBP-4
      using the LCR/Mel expression system. Using this system, we found that recombinant
      IGFBP-3 was secreted by Mel cells and had a glycosylation pattern similar to that
      of native IGFBP-3. Recombinant IGFBP-4 secreted from Mel cells had a molecular
      size identical to that of non-glycosylated native IGFBP-4. The binding kinetics
      of recombinant IGFBPs was measured using a solid-phase ligand-binding assay, an
      in vitro solution-binding assay, and a cellular proliferation assay. IGF-I bound
      with high affinity to recombinant IGFBP-3 and IGFBP-4 with K(D)s of <0.25 nmol.
      As reported for native IGFBPs, IGF-II bound with affinity higher than IGF-I to
      recombinant IGFBP-3 and IGFBP-4 (K(D) of <0.05 nmol). Recombinant IGFBP-3 and
      IGFBP-4 were found to inhibit the IGF-induced proliferation of an NIH3T3 cell
      line engineered to overexpress the IGF-I receptor. We have compared the binding
      kinetics of Mel cell-expressed IGFBPs with that of recombinant protein expressed
      in Escherichia coli and found them to be equivalent. Here, we show that the
      LCR/Mel expression system represents an effective route for expression of
      biologically active IGFBPs.

PMID- 12509979
TI  - Cloning, expression, purification, and crystallisation of HIV-2 reverse
      transcriptase.
AB  - A purification procedure is described for the isolation of recombinant HIV-2
      reverse transcriptase expressed in Escherichia coli. The p68 subunit is
      expressed, in the absence of induction, and use of a heparin-Sepharose column
      produces substantially pure protein. Concentration of the homodimeric p68 reverse
      transcriptase pool, followed by incubation at room temperature for several days,
      results in full conversion by E. coli proteases to the heterodimer (p68/p55).
      This extended incubation simplifies the purification process and improves the
      yield of heterodimeric reverse transcriptase, which shows a truncation of the
      smaller subunit to 427 residues. The protein is then purified further by
      hydroxyapatite and gel-filtration chromatography to homogeneity. The HIV-2 RT is
      active and has been used to produce crystals that diffract to beyond 3.0 A.

PMID- 12509980
TI  - Expression and purification of functional, recombinant Trypanosoma cruzi
      complement regulatory protein.
AB  - The complement regulatory protein (CRP) of Trypanosoma cruzi is a developmentally
      regulated glycosylphosphatidylinositol (GPI)-anchored membrane protein that
      protects the parasite from complement-mediated killing, and is an important
      virulence determinant of the microorganism. CRP binds human complement components
      C3b and C4b to restrict activation of the complement cascade. Here, we report
      production of functional, recombinant T. cruzi CRP in mammalian cells and a one
      step purification of the recombinant protein. Exchange of the crp DNA sequence
      encoding the carboxy-terminal GPI signal sequence with the corresponding sequence
      of decay accelerating factor (DAF) was necessary for recognition, cleavage, and
      addition of GPI in mammalian cells. CRP production was assessed in two mammalian
      cell lines with crp-daf gene expression driven by three different transcription
      control regions: Rous sarcoma virus long terminal repeat, cytomegalovirus (CMV)
      immediate early gene, and chicken beta-actin promoter/CMV enhancer. We present
      evidence that CRP produced in transfected Chinese hamster Ovary (CHO) cells was
      functional and protected the cells from complement-mediated lysis. To facilitate
      purification of the recombinant protein, a hexahistidyl tag was incorporated at
      3(') end of the cDNA upstream of the GPI anchor addition sequence. An additional
      histidine fusion construct was made that allowed for secretion and recovery of
      recombinant protein from culture supernatant fluid. Both membrane and secreted
      forms of the protein were purified in one step by nickel nitrilotriacetic acid.
      The production and purification of functionally active CRP in a non-infectious
      expression system will allow for structure and function studies aimed at
      identifying the active site(s) of this protein.

PMID- 12509981
TI  - Purification and diagnostic utility of a recombinant hepatitis E virus capsid
      protein expressed in insect larvae.
AB  - We report here the expression and purification of a truncated form of the
      hepatitis E virus ORF2 protein (ORF2delta111/deltaTM), from the fat bodies of
      Spodoptera litura larvae infected with a recombinant baculovirus. The purified
      protein migrated as a doublet of approximately 56 kDa on SDS-PAGE and was found
      to be glycosylated by staining with concanavalin A-linked horseradish peroxidase.
      The protein was used in a sensitive and specific enzyme-linked immunosorbent
      assay (ELISA) for the detection of antibodies to HEV. The results showed complete
      concordance with those obtained using a commercial kit for the detection of anti
      HEV antibodies. Antigen expression in the insect larvae system presents a rapid
      and low-cost method that obviates the need for expensive tissue culture scale-ups
      or special equipment.

PMID- 12509982
TI  - Expression and characterization of frog peptidylglycine alpha-hydroxylating
      monooxygenase.
AB  - We report here a recombinant Chinese hamster ovary cell system,which is able to
      stably express frog peptidylglycine alpha-hydroxylating monooxygenase (PHM, EC
      1.14.17.3), the first enzyme responsible for the formation of peptide C-terminal
      amide. This system excreted PHM mostly into the medium and almost no PHM activity
      was detected in the cell lysate. Three differentiation inducers were examined to
      determine whether or not they would enhance the PHM expression. Addition of 4mM
      sodium butyrate into the medium increased the expression of PHM activity about 4
      fold at 48 h after addition. Increases of about 2-fold were observed in the cases
      of sodium propionate or N,N(')-hexamethylene-bis-acetamide. Through a three-step
      purification procedure, we obtained 5mg purified PHM, which showed a single band
      at 40 kDa on SDS-PAGE, from 2-L of conventional monolayer culture medium. The
      reactions with three synthetic substrates, D-Tyr-Val-Gly, N-trinitrophenyl-D-Tyr
      Val-Gly (TNPYVG), and hippuric acid (HA), were characterized. Of these, TNPYVG
      was the most active substrate. The pH optima for TNPYVG and HA were pH 5-6, while
      that for D-Tyr-Val-Gly was pH 7.5. There is a possibility that the substrate N
      terminal structure may affect the interaction between the substrate and the
      enzyme catalytic site.

PMID- 12509983
TI  - Expression of a fully functional cd1 nitrite reductase from Pseudomonas
      aeruginosa in Pseudomonas stutzeri.
AB  - Nitrite reductases are redox enzymes catalysing the one electron reduction of
      nitrite to nitrogen monoxide (NO) within the bacterial denitrification process.
      We have cloned the gene for cd(1) nitrite reductase (Pa-nirS) from Pseudomonas
      aeruginosa into the NiRS(-) strain MK202 of Pseudomonas stutzeri and expressed
      the enzyme under denitrifying conditions. In the MK202 strain, denitrification is
      abolished by the disruption of the endogenous nitrite reductase gene; thus, cells
      can be grown only in the presence of oxygen. After complementation with Pa-nirS
      gene, cells supplemented with nitrate can be grown in the absence of oxygen. The
      presence of nitrite reductase was proven in vivo by the demonstration of NO
      production, showing that the enzyme was expressed in the active form, containing
      both heme c and d(1). A purification procedure for the recombinant PaNir has been
      developed, based on the P. aeruginosa purification protocol; spectroscopic
      analysis of the purified protein fully confirms the presence of the d(1) heme
      cofactor. Moreover, the functional characterisation of the recombinant NiR has
      been carried out by monitoring the production of NO by the purified NiR enzyme in
      the presence of nitrite by an NO electrode. The full recovery of the
      denitrification properties in the P. stutzeri MK202 strain by genetic
      complementation with Pa-NiR underlines the high homology between enzymes of
      nitrogen oxianion respiration. Our work provides an expression system for cd(1)
      nitrite reductase and its site-directed mutants in a non-pathogenic strain and is
      a starting point for the in vivo study of recombinant enzyme variants.

PMID- 12509984
TI  - Bacterial expression, purification, and in vitro N-myristoylation of fusion
      hepatitis B virus preS1 with the native-type N-terminus.
AB  - Very low-level expression of hepatitis B virus (HBV) preS1 with the native-type N
      terminus hampered the biochemical and functional studies on its myristoylation.
      In the present study, the fusion HBV preS1 with the native-type N-terminus and a
      His6-Tag fused to C-terminus (HBV preS1-HT) was highly expressed in Escherichia
      coli. This was due to an introduced mutation of the rare codon GGA found in the
      HBV preS1 to the codon preferred by E. coli, GGU. The protein was rapidly
      purified from bacterial lysate by Ni-IDA affinity chromatography. The
      experimental assays using 3H-labeled substrate demonstrate that the purified HBV
      preS1-HT can be effectively N-myristoylated by recombinant human protein N
      myristoyltransferase (NMT) in vitro.

PMID- 12509985
TI  - EGFP as a fusion partner for the expression and organic extraction of small
      polypeptides.
AB  - Green fluorescent protein (GFP) is widely used as an excellent reporter module of
      the fusion proteins. The unique structure of GFP allows isolation of the active
      fluorescent protein directly from the crude cellular sources by extraction with
      organic solvents. We demonstrated the stable expression of four short
      polypeptides fused to GFP in Escherichia coli cells, including antimicrobial
      cationic peptides, which normally kill bacteria. EGFP module protected fusion
      partners from the intracellular degradation and allowed the purification of the
      chimerical proteins by organic extraction. The nature of the polypeptide fused to
      GFP, as opposed to the order of GFP and the polypeptide modules in the fusion
      protein, influenced the efficiency of the described purification technique.

PMID- 12509986
TI  - Purification and characterization of catalytic domains of gelatinase A with or
      without fibronectin insert for high-throughput inhibitor screening.
AB  - Gelatinase A represents an attractive therapeutic target for cancer invasion and
      metastasis. In order to screen for gelatinase A inhibitors, we have cloned,
      overexpressed in a bacterial system, and purified the catalytic domain of human
      gelatinase A with (GaCDfn) or without (GaCD) fibronectin-like insert. GaCDfn and
      GaCD were purified to homogeneity and refolded in vitro. GaCDfn was refolded to a
      stable and active form in the presence of calcium and zinc ions. GaCD was
      refolded through direct dialysis against Tris-HCl (pH 7.5) buffer without calcium
      and zinc ions. GaCD is unstable in the presence of calcium and zinc ions. The
      enzymatic activities of GaCDfn and GaCD require calcium and zinc ions, but high
      concentration of zinc and calcium ions inhibited the activities. The GaCDfn and
      GaCD cleaved several synthetic substrates including a chromogenic thiopeptolide
      (TPL) and fluorogenic peptides with optimal activity around pH 7.5. Moreover,
      GaCDfn and GaCD cleave gelatin and collagen VII and display similar cleavage
      patterns on the gel, but the digestion rate of these protein substrates by GaCD
      is apparently slower than GaCDfn. EDTA, 1,10-phenanthroline, and reference
      inhibitors potently blocked GaCDfn and GaCD enzymatic activities. A set of 3596
      compounds from our center collection were screened by using GaCDfn and GaCD to
      cleave TPL. Further analysis by using MMP inhibitors indicated there is a
      correlation between IC(50) values on GaCDfn and GaCD. A few compounds with
      selectivity toward gelatinase A catalytic domain were identified for structure
      modification.

PMID- 12509987
TI  - Structural investigation of mutant Mycobacterium smegmatis arylamine N
      acetyltransferase: a model for a naturally occurring functional polymorphism in
      Mycobacterium tuberculosis arylamine N-acetyltransferase.
AB  - Arylamine N-acetyltransferase (NAT) acetylates the front-line anti-tuberculosis
      drug isoniazid (INH) and has been identified in Mycobacterium tuberculosis. A
      naturally occurring single nucleotide polymorphism (SNP) was recently found in
      the NAT gene in clinical isolates of M. tuberculosis. The nucleotide change from
      G-->A (619) produces an amino acid change Gly(207) Arg, which appears to reduce
      the activity of the NAT from M. tuberculosis (TBNAT). It has not been possible to
      generate sufficient soluble recombinant TBNAT for 3D structural studies.
      Therefore, Mycobacterium smegmatis NAT (SMNAT), which has 60% identity to TBNAT
      and has Gly at 207, was used as a model to investigate the possible structural
      effects of the G-->A 619 SNP. The mutant form of SMnat (SM207Rnat) was
      constructed by in vitro site-directed mutagenesis and was heterologously
      expressed with an N-terminal His tag in Escherichia coli, for comparison with the
      SMNAT. Both recombinant SMNATs were purified using Ni affinity chromatography and
      treated with thrombin to cleave the tag. Both proteins were produced with average
      yields of over 10 mg/L and were active. Substrate specificity and thermal
      stability of SM207RNAT were assessed and compared with the wild type SMNAT using
      kinetic assays and circular dichroism spectroscopy. SM207RNAT was crystallised
      and a data set of 2.00 A resolution was obtained. The SM207RNAT had different
      substrate specificities to the wild type protein and the 3D structures revealed
      that the Gly(207) Arg mutation caused slight changes in the orientation of
      His(203) in SMNAT.

PMID- 12509988
TI  - Expression and purification of recombinant immunotoxin--a fusion protein
      stabilizes a single-chain Fv (scFv) in denaturing condition.
AB  - Carcinoembryonic antigen (CEA) is expressed at greatly increased levels in nearly
      all human colorectal carcinomas. Anti-CEA antibodies have been proved to be
      useful for targeting several cancer types known to express CEA. A recombinant
      immunotoxin was constructed, in which the cell-binding domain of Pseudomonas
      exotoxin (PE) was replaced with the single-chain Fv (scFv) of anti-CEA monoclonal
      antibody for targeting to colorectal carcinomas. This single-chain immunotoxin
      was expressed in E. coli and purified under denaturing condition of 6M guanidine
      hydrochloride (GuHCl). It was found that the immunotoxin maintains a binding
      activity in denaturing condition of 6M GuHCl and the fused PE contributes to the
      stability of immunotoxin in such condition. Dialysis against PBS buffer after
      purification under 6M GuHCl keeps the binding activity of immunotoxin.

PMID- 12509989
TI  - DNA polymerase III of Enterococcus faecalis: expression and characterization of
      recombinant enzymes encoded by the polC and dnaE genes.
AB  - Enterococcus faecalis (Ef) dnaE and polC, the respective genes encoding the DNA
      replication-specific DNA polymerase III E and DNA polymerase III C, were cloned
      and engineered for expression in Escherichia coli as hexahistidine (his6)-tagged
      recombinant proteins. Each gene expressed a catalytically active DNA polymerase
      of the expected molecular weight. The recombinant polymerases were purified and
      each was characterized with respect to catalytic properties, inhibitor
      sensitivity, and recognition by specific antibody raised against the
      corresponding DNA polymerase III of the model Gram-positive (Gr(+)) organism,
      Bacillus subtilis (Bs). In conclusion, the properties of each Enterococcus
      polymerase enzymes were similar to those of the respective B. subtilis enzymes.

PMID- 12509990
TI  - Optimized bacterial expression of human apolipoprotein A-I.
AB  - Apolipoprotein A-I (apoA-I) serves critical functions in plasma lipoprotein
      metabolism as a structural component of high density lipoprotein, activator of
      lecithin:cholesterol acyltransferase, and acceptor of cellular cholesterol as
      part of the reverse cholesterol transport pathway. In an effort to facilitate
      structure:function studies of human apoA-I, we have optimized a plasmid vector
      for production of recombinant wild type (WT) and mutant apoA-I in bacteria. To
      facilitate mutagenesis studies, subcloning, and DNA manipulation, numerous silent
      mutations have been introduced into the apoA-I cDNA, generating 13 unique
      restriction endonuclease sites. The coding sequence for human apoA-I has been
      modified by the introduction of additional silent mutations that eliminate 18
      separate codons that employ tRNAs that are of low or moderate abundance in
      Escherichia coli. Yields of recombinant apoA-I achieved using the optimized cDNA
      were 100+/-20 mg/L bacterial culture, more than fivefold greater than yields
      routinely obtained with the original cDNA. Site-directed mutagenesis of the apoA
      I cDNA was performed to generate a Glu2Asp mutation in the N-terminal sequence of
      apoA-I. This modification, which creates an acid labile Asp-Pro peptide bond
      between amino acids 2 and 3, permits specific chemical cleavage of an N-terminal
      His-Tag fusion peptide used for rapid protein purification. The product protein's
      primary structure is identical to WT apoA-I in all other respects. Together,
      these changes in apoA-I cDNA and bacterial expression protocol significantly
      improve the yield of apoA-I protein without compromising the relative ease of
      purification.

PMID- 12509991
TI  - Expression, purification, and characterization of human tyrosyl-tRNA synthetase.
AB  - Human tyrosyl-tRNA synthetase is a homodimeric enzyme and each subunit is near 58
      KD. It catalyzes the aminoacylation of tRNA(Tyr) by L-tyrosine. The His(6)-tagged
      human TyrS gene was obtained by RT-PCR from total RNA of human lung giant-cell
      cancer strain 95 D. It was confirmed by sequencing and cloned into the expression
      vector pET-24 a (+) to yield pET-24 a (+)-HTyrRS, which was transfected into
      Escherichia coli BL21-CodonPlus-RIL. The induced-expression level of His(6)
      tagged human TyrRS was about 24% of total cell proteins under IPTG inducing. The
      recombinant protein was conveniently purified in a single step by metal (Ni(2+))
      chelate affinity chromatography. About 22.3mg purified enzyme could be obtained
      from 1L cell culture. The k(cat) value of His(6)-tagged human TyrRS in the second
      step of tRNA(Tyr) aminoacylation was 1.49 s(-1). The K(m) values of tyrosine and
      tRNA(Tyr) were 0.3 and 0.9 microM. Six His residues at the C terminus of human
      TyrRS have little effect on the activities of the enzyme compared with other
      eukaryotic TyrRSs.

PMID- 12509992
TI  - Inhibition of tobacco etch virus protease activity by detergents.
AB  - Affinity tags such as polyhistidine greatly facilitate recombinant protein
      production. The solubility of integral membrane proteins is maintained by the
      formation of protein-detergent complexes (PDCs), with detergent present at
      concentration above its critical micelle concentration (CMC). Removal of the
      affinity tag necessitates inclusion of an engineered protease cleavage site. A
      commonly utilized protease for tag removal is tobacco etch virus (TEV) protease.
      TEV is available in a recombinant form (rTEV) and frequently contains its own
      polyhistidine affinity tag for removal after use in enzymatic digestion.
      Proteolytic cleavage of the tagged domain is carried out by incubation of the
      protein with rTEV protease. We have observed that the efficiency of rTEV
      digestion decreases significantly in the presence of a variety of detergents
      utilized in purification, crystallization, and other biochemical studies of
      integral membrane proteins. This reduction in protease activity is suggestive of
      detergent-induced inhibition of rTEV. To test this hypothesis, we examined the
      effects of detergents upon the rTEV proteolytic digestion of a soluble fusion
      protein, alpha(1) platelet activating factor acetylhydrolase (PAFAHalpha(1)).
      Removal of a hexahistidine amino-terminal affinity tag has been characterized in
      the presence of 16 different detergents at concentrations above their respective
      CMCs. Our data indicate that half of the detergents tested reduce the activity of
      rTEV and that these detergents should be avoided or otherwise accounted for
      during rTEV digestion of recombinant integral membrane proteins.

PMID- 12509993
TI  - Design, preparation, and characterization of mixed dimers of inducible nitric
      oxide synthase oxygenase domains.
AB  - A limitation of site-directed mutagenesis of homodimeric proteins is that both
      subunits will carry the same mutation. We have devised a way to prepare mixed
      dimers, in which only one chain bears a desired mutation, or each chain can bear
      a different mutation. Using the inducible nitric oxide oxygenase domain as a
      model, our strategy focused on the co-expression of two differentially tagged
      versions of the oxygenase domain, with isolation of the desired mixed dimer in
      two chromatography steps. We evaluated expression vectors encoding polyhistidine
      (His(6)), cellulose binding domain, glutathione-S-transferase, and polyglutamate
      (Glu(7))-tagged versions of the oxygenase domain for satisfactory levels of
      soluble protein expression and for their ability to form mixed dimers. The
      combination of His(6)- and Glu(7)-tagged subunits was successful in both
      respects, and the mixed dimers could be separated from either form of homodimer
      by sequential immobilized metal affinity chromatography and anion exchange
      chromatography. The UV-Vis spectrum, substrate binding properties, and enzymatic
      activity were not altered in the mixed dimer wild-type (His(6)/Glu(7)) compared
      to the two homodimers (His(6)/His(6) and Glu(7)/Glu(7)). We then characterized a
      mixed dimer variant in which one chain contained an E371A substitution (which
      prevents binding of the substrate L-arginine) while the other subunit was left
      unaltered. This species binds L-arginine and has about one-half the activity of
      the wild-type homodimer. Mutants known to destabilize the iNOS dimer (E411A,
      D454A, and W188F) were also investigated; in these cases co-expression with the
      wild-type subunit did not lead to the formation of stable mixed dimers.

PMID- 12509994
TI  - Cloning, expression, and efficient purification in Escherichia coli of a
      halophilic nucleoside diphosphate kinase from the moderate halophile Halomonas
      sp. #593.
AB  - Most typical halophilic enzymes from extremely halophilic archaea require high
      concentrations of salt for their activity and stability. These enzymes are
      inactive in Escherichia coli unless refolded in the presence of salts in vitro.
      In this report, we describe cloning of the ndk gene of nucleoside diphosphate
      kinase from a moderately halophilic eubacterium and overexpression of the protein
      in E. coli as an N-terminal hexa-His fusion to facilitate its purification on Ni
      NTA affinity resin. We demonstrate evidence that the protein is properly folded
      and exhibits the same specific activity and stability as the native protein from
      Halomonas cells.

PMID- 12509995
TI  - Effects of codon usage versus putative 5'-mRNA structure on the expression of
      Fusarium solani cutinase in the Escherichia coli cytoplasm.
AB  - Matching the codon usage of recombinant genes to that of the expression host is a
      common strategy for increasing the expression of heterologous proteins in
      bacteria. However, while developing a cytoplasmic expression system for Fusarium
      solani cutinase in Escherichia coli, we found that altering codons to those
      preferred by E. coli led to significantly lower expression compared to the wild
      type fungal gene, despite the presence of several rare E. coli codons in the
      fungal sequence. On the other hand, expression in the E. coli periplasm using a
      bacterial PhoA leader sequence resulted in high levels of expression for both the
      E. coli optimized and wild-type constructs. Sequence swapping experiments as well
      as calculations of predicted mRNA secondary structure provided support for the
      hypothesis that differential cytoplasmic expression of the E. coli optimized
      versus wild-type cutinase genes is due to differences in 5(') mRNA secondary
      structures. In particular, our results indicate that increased stability of 5(')
      mRNA secondary structures in the E. coli optimized transcript prevents efficient
      translation initiation in the absence of the phoA leader sequence. These results
      underscore the idea that potential 5(') mRNA secondary structures should be
      considered along with codon usage when designing a synthetic gene for high level
      expression in E. coli.

PMID- 12509996
TI  - Expression, refolding, and activation of the catalytic domain of human blood
      coagulation factor XII.
AB  - Human blood coagulation factor XII (FXII; 80 kDa) contains a C-terminal serine
      protease zymogen domain, which becomes activated upon contacting a negative
      surface. Activated FXII (alphaFXIIa) brings about reciprocal activation of FXII
      and kallikrein that by further hydrolysis produces the free catalytic domain
      (betaFXIIa; 28 kDa). Increased levels of alphaFXIIa are associated with coronary
      heart disease, sepsis, and diabetes. Biophysical investigation of the structural
      basis of activation, substrate specificity, and regulation of FXII requires an
      efficient bacterial system for producing the wild-type and mutant recombinant
      proteins. Here, the cDNA of the zymogen domain of FXII (betaFXII) was cloned into
      the pET-28a(+) vector and the plasmid was transformed into Escherichia coli
      strain BL21 (DE3) and overexpressed. The multi-disulfide, recombinant protein,
      His(6)-betaFXII (rbetaFXII), expressed as an inclusion body, was purified by
      means of a Ni(2+)-charged resin. The matrix-bound rbetaFXII was subjected to
      refolding with the glutathione redox system and activated by the in vivo
      activator, kallikrein. The active form, rbetaFXIIa, obtained in milligram
      quantities, exhibited similar structural and comparable functional properties
      relative to human betaFXIIa, as indicated by circular dichroism spectroscopy and
      kinetics of substrate hydrolysis. Thermodynamics of enzyme:inhibitor complex
      formation, including the expected 1:1 stoichiometry, was determined for
      rbetaFXIIa by isothermal calorimetric titration with a specific recombinant
      protein inhibitor, Cucurbita maxima trypsin inhibitor-V (rCMTI-V; 7kDa).

PMID- 12509997
TI  - High yield expression and single-step purification of Toxoplasma gondii SAG1,
      GRA1, and GRA7 antigens in Escherichia coli.
AB  - This report describes a simple, highly efficient and reproducible method for
      obtaining large quantities of highly pure recombinant Toxoplasma gondii antigens,
      which can be used for diagnostic application. The obtained T. gondii SAG1, GRA1,
      and GRA7 antigens (as fusion proteins), expressed in Escherichia coli, contained
      polyhistidine tags at the N- and C-ends that allowed single-step isolation by
      metal-affinity chromatography on Ni(2+)-IDA-Sepharose columns. The
      immunoreactivity of the recombinant antigens was tested in an enzyme-linked
      immunosorbent assay (ELISA) format for potential application in the serodiagnosis
      of T. gondii infection.

PMID- 12509998
TI  - Cloning, overexpression, and purification of functional human purine nucleoside
      phosphorylase.
AB  - Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of the N
      ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency
      due to mutations in the gene encoding for human PNP causes T-cell deficiency as
      the major physiological defect. Inappropriate activation of T-cells has been
      implicated in several clinically relevant human conditions such as transplant
      tissue rejection, psoriasis, rheumatoid arthritis, lupus, and T-cell lymphomas.
      Human PNP is therefore a target for inhibitor development aiming at T-cell immune
      response modulation. In addition, bacterial PNP has been used as reactant in a
      fast and sensitive spectrophotometric method that allows both quantitation of
      inorganic phosphate (P(i)) and continuous assay of reactions that generate P(i)
      such as those catalyzed by ATPases and GTPases. Human PNP may therefore be an
      important biotechnological tool for P(i) detection. However, low expression of
      human PNP in bacterial hosts, protein purification protocols involving many
      steps, and low protein yields represent technical obstacles to be overcome if
      human PNP is to be used in either high-throughput drug screening or as a reagent
      in an affordable P(i) detection method. Here, we describe PCR amplification of
      human PNP from a liver cDNA library, cloning, expression in Escherichia coli
      host, purification, and activity measurement of homogeneous enzyme. Human PNP
      represented approximately 42% of total soluble cell proteins with no induction
      being necessary to express the target protein. Enzyme activity measurements
      demonstrated a 707-fold increase in specific activity of cloned human PNP as
      compared to control. Purification of cloned human PNP was achieved by a two-step
      purification protocol, yielding 48 mg homogeneous enzyme from 1L cell culture,
      with a specific activity value of 80 Umg(-1).

PMID- 12509999
TI  - Cloning, expression, and purification of His-tagged rat mevalonate kinase.
AB  - Mevalonate kinase catalyzes the phosphorylation of mevalonic acid to form
      mevalonate 5-phosphate, which plays a key role in regulating cholesterol
      biosynthesis in animal cells. Deficiency of mevalonate kinase activity in the
      human body has been linked to mevalonic aciduria and hyperimmunoglobulinemia
      D/periodic fever syndrome (HIDS). We cloned the gene of rat mevalonate kinase
      into a bacterial expression vector pLM1 with six continuous histidine codons
      attached to the 5(') of the gene. The cloned gene was overexpressed in
      Escherichia coli and the soluble protein was purified with a nickel HiTrap
      chelating metal affinity column in 90% yield to apparent homogeneity. The
      purified rat mevalonate kinase had a dimeric structure composed of identical
      subunits. Based on SDS-PAGE, the subunit was 42 kDa. The specific activity of the
      purified His-tagged rat mevalonate kinase was 32.7 micromol/min/mg and the
      optimal pH was found to be 7.0-8.0 in phosphate buffer. The Michaelis constant
      K(M) was 35 microM for (RS)-mevalonate and 953 microM for ATP, respectively. The
      V(max) was determined to be 38.7 micromol/min/mg. The overexpression of rat
      mevalonate kinase in E. coli and one-step purification of the highly active rat
      mevalonate kinase will facilitate further our investigation of this enzyme
      through site-directed mutagenesis and enzyme-catalyzed reactions with substrate
      analogs.

PMID- 12510000
TI  - Analysis of human alpha-thrombin by hydrophobic interaction high-performance
      liquid chromatography.
AB  - The major active form of human thrombin, alpha-thrombin, was analyzed by
      hydrophobic interaction high-performance liquid chromatography (HIC-HPLC). The
      chromatographic system included a polymeric phenyl column and elution was
      performed by a gradient, 2-0M sodium chloride (5-20 min). Total analysis time was
      30 min per injection. By this method, a good resolution between alpha-thrombin
      and the proteolytically modified thrombin forms, beta- and gamma-thrombin, was
      obtained. In addition, the thrombin preforms, prothrombin, prethrombin 1, and
      prethrombin 2, were also resolved from alpha-thrombin in the system. The results
      from the HIC method were compared to those obtained from non-reducing sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. By this high-resolution
      chromatographic method, the rapid analysis of purified alpha-thrombin is
      possible.

PMID- 12510001
TI  - Expression of recombinant Pseudomonas stutzeri di-heme cytochrome c4 by high-cell
      density fed-batch cultivation of Pseudomonas putida.
AB  - The gene of the di-heme protein cytochrome c(4) from Pseudomonas stutzeri was
      expressed in Pseudomonas putida. High-yield expression of the protein was
      achieved by high-cell-density fed-batch cultivation using an exponential glucose
      feeding strategy. The recombinant cytochrome c(4) protein was purified to
      apparent homogeneity and analyzed by electronic absorption spectroscopy, nanoflow
      electrospray ionization time-of-flight mass spectrometry, and electrochemistry.
      Cyclic voltammograms and UV-vis electronic absorption spectra were
      indistinguishable from the equivalent data of native P. stutzeri cytochrome c(4).
      Furthermore, the calculated and experimentally determined molecular masses of
      recombinant cytochrome c(4) were identical. Biochemical characterization of both
      wild-type and mutant derivatives of the protein will be greatly enhanced and
      facilitated by the described high-yield fermentation and rapid isolation
      procedure.

PMID- 12510002
TI  - Egg-matrix for large-scale single-step affinity purification of plant lectins
      with different carbohydrate specificities.
AB  - Hen eggs represent an easily available and inexpensive source of glycoproteins
      expressing a variety of sugars. Egg glycoproteins might therefore be exploited to
      purify by affinity chromatography carbohydrate-binding proteins (lectins) with
      different specificities. A method to generate an affinity matrix from hen eggs is
      described. The matrix was assayed for its ability to purify in a single step
      biologically active phytohemagglutinin, wheat germ agglutinin, lentil lectin, and
      peanut agglutinin. Milligrams of purified lectins per gram of matrix was
      obtained, with the only exception of peanut agglutinin that was not efficiently
      retained into the affinity column. Hen egg chromatography is a relatively simple,
      fast, and reproducible method to purify high amount of plant lectins.

PMID- 12510003
TI  - Expression, purification, crystallization, and preliminary X-ray analysis of
      recombinant human saposin B.
AB  - Saposin B (also known as cerebroside sulfate activator or CSAct) is a small non
      enzymatic glycoprotein required for the breakdown of cerebroside sulfates
      (sulfatides) in lysosomes. Saposin B contains three intramolecular disulfide
      bridges, exists as a dimer and is remarkably heat, protease, and pH stable. We
      have expressed the protein in a thioredoxin reductase deficient strain of
      Escherichia coli and purified the protein by heat treatment, followed by ion
      exchange, gel filtration, and hydrophobic interaction chromatographies. The
      protein is properly folded as judged by the observed disulfide bond topology, the
      hydrogen-deuterium exchange rate, and the level of stimulation of sulfatide
      hydrolysis by arylsulfatase A. Crystals of human saposin B were grown by vapor
      diffusion and diffract to a resolution of 2.2A. Despite obtaining only
      merohedrally twinned P3(1) native crystals, an untwined seleomethionine
      substituted crystal belonging to space group P3(1)21 was also grown. The three
      dimensional structure of saposin B protein will provide insights into how this 79
      amino acid protein is able to solubilize relatively large membrane-bound lipid
      ligands.

PMID- 12510004
TI  - The cryopreservation of spermatozoa of the burbot, Lota lota (Gadidae,
      Teleostei).
AB  - The cryopreservation of spermatozoa of a teleost fish, the burbot, Lota lota
      (Gadidae) was investigated. Cryopreserved semen had the highest motility rate
      (46.6+/-8.0%, fresh semen control 86.5+/-8.2%) and fertility (78.1+/-2.7% embryo
      survival in hatching stage, fresh semen control 82.2+/-2.9%) when 10% methanol,
      1.5% glucose and 7% hen egg yolk were used as cryoprotectants. Freezing was
      performed in 0.5-ml straws in the vapour of liquid nitrogen at 1cm above the
      level of liquid nitrogen and thawing in water at 25 degrees C for 20s. For
      optimal fertilization cryopreserved semen was first mixed with the eggs and then
      25 or 50 mmol/L NaCl solution (pH 8.5) was added at a ratio of 1:24 (semen:saline
      solution). Under these conditions fertilization ratios in the range of fresh
      semen control were obtained at minimal sperm to egg ratios of 1.7 x 10(6):1.
      Fertilization with cryopreserved semen had no influence on the embryonic
      development, as the ratio of embryos which stopped development and the ratio of
      embryonic malformations were similar to fresh semen.

PMID- 12510005
TI  - Defined media for vitrification, warming, and rehydration: effects on post-thaw
      protein synthesis and viability of in vitro derived ovine embryos.
AB  - The purpose of this study was to assess the viability (rates of re-expanding and
      hatching in vitro), of in vitro derived ovine blastocysts using vitrification and
      warming/rehydration media containing fetal calf serum (20% FCS) or polyvinyl
      alcohol (0.1% PVA), and the incorporation of labelled methionine in protein
      synthesised during the first 4h after cryopreservation. In experiment 1, after 60
      h culture in TCM-199 supplemented with 10% FCS, the hatching rates of blastocysts
      that had been vitrified, warmed, and rehydrated in media containing only PVA
      (p/p) were significantly (P<0.05) lower than those vitrified in medium containing
      PVA with warming and rehydration in medium containing FCS (p/s). Blastocysts that
      were vitrified in medium containing FCS and warmed and rehydrated in medium with
      PVA (s/p) had hatching rates that were significantly lower (P<0.01) than those
      vitrified, warmed, and rehydrated in media with only FCS (s/s). After warming,
      the number of dead cells in the p/p group was significantly (P<0.05) lower than
      in all other groups. In experiment 2, the [35S]methionine uptake by embryonic
      cells of the s/p group was significantly (P<0.01) higher than in other groups.
      The incorporation of labelled methionine into newly synthesised proteins was
      significantly lower in the p/p group (P<0.01) than in all other groups. No
      differences in the newly synthesised proteins were observed between groups. In
      conclusion, these results suggest that it is possible to replace serum with
      defined macromolecules in vitrification and warming/rehydration media for in
      vitro derived ovine blastocysts but this leads to a decrease in viability and a
      reduction in protein synthesis after warming.

PMID- 12510008
TI  - Heritability of cortisol levels: review and simultaneous analysis of twin
      studies.
AB  - Cortisol has a pivotal role in physical and mental health, but relatively few
      studies have paid attention to individual differences in cortisol levels and the
      etiology of these differences, in particular their possible genetic basis. In
      this article we review the existing literature on the heritability of cortisol
      levels. Most of the studies, which have been carried out in genetically
      informative samples, lack methodological consistency with regard to frequency and
      timing of sample collection. The circadian rhythm in cortisol levels was often
      not taken into account. A power analysis shows that none of these studies used
      adequate sample sizes to distinguish genetic from shared environmental influences
      as a cause for familial aggregation. Results of a simultaneous analysis of 5
      comparable twin studies suggest a heritability of 62%. Hence, we conclude that,
      to understand the contribution of genetic and (shared) environmental influences
      to variation in basal cortisol levels, future studies should be designed more
      rigorously with strict collection and sampling protocols, sufficient sample size
      and repeated measures across multiple days.

PMID- 12510009
TI  - Neuroactive steroids: mechanisms of action and neuropsychopharmacological
      properties.
AB  - Steroids influence neuronal function through binding to cognate intracellular
      receptors which may act as transcription factors in the regulation of gene
      expression. In addition, certain so-called neuroactive steroids modulate ligand
      gated ion channels via non-genomic mechanisms. Especially distinct 3alpha-reduced
      metabolites of progesterone and deoxycorticosterone are potent positive
      allosteric modulators of gamma-aminobutyric acid type A (GABA(A)) receptors.
      However, also classical steroid hormones such as 17beta-estradiol, testosterone
      and progesterone are neuroactive steroids because they may act as functional
      antagonists at the 5-hydroxytryptamine type 3 (5-HT(3)) receptor, a ligand-gated
      ion channel or distinct glutamate receptors. A structure-activity relationship
      for the actions of a variety of steroids at the 5-HT(3) receptor was elaborated
      that differed considerably from that known for GABA(A) receptors. Although a
      bindings site for steroids at GABA(A) receptors is still a matter of debate,
      meanwhile there is also evidence that steroids interact allosterically with
      ligand-gated ion channels at the receptor membrane interface. On the other hand,
      also 3alpha-reduced neuroactive steroids may regulate gene expression via the
      progesterone receptor after intracellular oxidation into 5alpha-pregnane
      steroids. Animal studies showed that progesterone is converted rapidly into
      GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity
      in a dose-dependent fashion in male Wistar rats. Moreover, progesterone and
      3alpha-reduced neuroactive steroids produce a benzodiazepine-like sleep EEG
      profile in rats and humans. During major depression, there is a disequilibrium of
      such 3alpha-reduced neuroactive steroids which is corrected by successful
      treatment with antidepressant drugs. Neuroactive steroids may further be involved
      in the treatment of depression and anxiety with antidepressants in patients
      during ethanol withdrawal. Studies in patients with panic disorder suggest that
      neuroactive steroids may also play a role in modulating human anxiety. Both the
      genomic and non-genomic effects of steroids in the brain may contribute to the
      pathophysiology of psychiatric disorders and the mechanisms of action of
      antidepressants. Neuroactive steroids affect a broad spectrum of behavioral
      functions through their unique molecular properties and may represent a new
      treatment strategy for neuropsychiatric disorders.

PMID- 12510010
TI  - Hypothalamic-pituitary adrenal response to cholecystokinin-B receptor agonism is
      resistant to cortisol feedback inhibition.
AB  - Intravenous injection of the cholecystokinin (CCK)-B receptor agonist,
      pentagastrin, produces robust, dose-dependent release of adrenocorticotropin
      (ACTH) and cortisol, supporting the hypothesis that CCK-B agonists
      pharmacologically activate the hypothalamic-pituitary-adrenal (HPA) axis. The
      mechanism of activation and its physiological relevance remain uncertain.
      Preliminary data suggest that the ACTH response to pentagastrin may be
      differentiated from the response to exogenous corticotropin releasing hormone
      (CRH) by its relative resistance to cortisol feedback inhibition. To more
      directly test the relationship between cortisol levels and ACTH response to
      pentagastrin, this study examined responses to pentagastrin (a) during a peak (8
      a.m.) and a nadir (4 p.m.) period of endogenous cortisol secretion and (b) when
      cortisol levels were artificially reduced to low levels by administration of
      metyrapone. ACTH responses to pentagastrin were identical in the morning and
      afternoon, despite substantial differences in basal cortisol levels. Suppression
      of cortisol with metyrapone had little impact on ACTH response to pentagastrin.
      These data support the hypothesis that CCK-B receptor mediated activation of the
      HPA axis is relatively resistant to cortisol feedback inhibition. This
      differentiates it from CRH-mediated activation and raises the possibility that
      CCK could contribute to acute activation of the HPA axis even in the face of
      elevated basal cortisol levels, such as those seen in chronic stress or some
      psychiatric disorders.

PMID- 12510011
TI  - Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic
      men? A randomized double-blind trial.
AB  - Epidemiological and clinical studies have suggested that powerful cholesterol
      lowering may have adverse effects on mood and psychological well-being.
      Inhibition of cholesterol biosynthesis by simvastatin (a hydroxymethyl glutaryl
      coenzyme A reductase inhibitor) may also reduce steroid hormone biosynthesis. To
      explore if mood changes are related with steroid hormone levels, we designed a
      randomized double-blind placebo-controlled crossover trial. The separate and
      combined effects of a Mediterranean-type diet intervention and treatment with
      simvastatin 20 mg/day PO for 12 weeks were studied in 120 hypercholesterolemic
      but otherwise healthy middle-aged men. Psychological functioning was assessed
      with questionnaires, and steroid hormone levels in blood were assayed
      radioimmunologically before and after the treatments. Simvastatin resulted in a
      statistically significant increase of depression and somatization without changes
      in the anxiety, hostility or aggression scores. Mood changes seemed to be
      unrelated with the statistically significant but clinically insignificant decline
      in serum testosterone levels and unrelated with the increase in serum
      dehydroepiandrosterone levels.

PMID- 12510012
TI  - Influence of time of day on hypothalamic monoaminergic activity in early
      pregnancy: effect of a previous reproductive experience.
AB  - Several dopamine-related neurochemical and behavioral responses are influenced by
      the time of day. The light-dark shift is a major zeitgeber for various
      functionally important hypothalamic monoaminergic systems. However, these
      influences are modulated by reproductive state and by reproductive experience
      (RE) in females. Early pregnancy in rodents generates diurnal and nocturnal
      prolactin surges that are reduced in intensity in a second pregnancy. Dopamine
      (DA) is a major inhibitory factor of prolactin synthesis and secretion. Other
      neurotransmitters such as serotonin (5HT) and norepinephrine (NE) can modulate
      prolactin secretion as well. Previous works have demonstrated that RE induces
      changes in central concentrations of both dopamine and serotonin. In addition, RE
      modulates the responses of both dopaminergic and serotoninergic nerve terminals.
      The present investigation was designed to examine the possible effects of RE on
      hypothalamic concentrations of DA, NE, 5HT and their major metabolites
      homovanillic acid (HVA), 3-4-dihydroxyphenyl acetic acid (DOPAC), 3-methoxy
      mandelic acid (VMA) and 5-hydroxyindole 3-acetic acid (5HIAA), respectively.
      These parameters were measured in pregnant rats during the light-dark shift and
      the prolactin surges. Primi- and multigravid rats were sacrificed on the 7th-8th
      day of pregnancy between 1700 and 1900 h (light-dark shift and diurnal prolactin
      surge) or 0200 and 0400 h (nocturnal prolactin surge), and hypothalamic
      concentrations of DA, NE and 5HT and their metabolites were measured by high
      performance liquid chromatography coupled to an electrochemical detector (HPLC
      ED). Trunk blood was collected and serum prolactin measured by radioimmunoassay.
      The prolactin surge was confirmed and multigravid rats showed significantly lower
      serum prolactin levels as compared to primigravid rats between 0200 and 0400 h.
      During the light-dark shift DA and NE concentrations increased while DOPAC/DA,
      HVA/DA and 5HIAA/5HT ratios decreased in multigravid rats compared to primigravid
      rats. Except for 5HIAA/5HT, these differences were not observed during the
      prolactin nocturnal surge. These results suggest that a previous reproductive
      experience induces central functional changes during pregnancy which are
      expressed differently according to the time of day.

PMID- 12510013
TI  - Body weight gain and diurnal differences of corticosterone changes in response to
      acute and chronic stress in rats.
AB  - Plasmatic levels of corticosterone display a circadian rhythm, with the higher
      values occurring during the dark phase in nocturnally feeding animals. Stressful
      situations induce a rise of corticosterone levels and this endocrine response to
      stress also presents circadian variations. The higher increase of corticosterone
      in response to stress occurs when the hormone is in its lower circadian level,
      and the minimum responses occurring at the peak. Since it has been shown that
      plasma hormones respond differently to different stressors, in the present study,
      we compared the acute and chronic effects of four different stressors: electric
      foot shocks (3 mA, 1/s, 5 min), immobilization during two hours or six hours, and
      immersion in cold water (15 degrees C) for 15 min. Stressors were applied, both
      acutely and chronically (during 4, 12 and 20 days) at the onset of the light
      phase as well as at the onset of the dark phase of the light/dark cycle. Body
      weight was assessed every day, and at the end of the manipulations plasmatic
      corticosterone levels were determined from the trunk blood. Adrenal and
      testicular weights were also assessed. Acute exposure to stressors increased
      plasmatic corticosterone levels significantly when the stressors were applied at
      the beginning of the light phase of the cycle. In the dark phase, only two hours
      of immobilization and immersion in cold water caused an increase in plasmatic
      corticosterone. With repeated exposure, electric foot shocks failed to induce
      significant changes in corticosterone levels in any phase of the light-dark
      cycle. Immobilization stress induced a significant rise in corticosterone levels
      only when the stressor was applied during the light phase. Immersion in cold
      water elicited a clear increase in plasmatic corticosterone levels in all the
      periods tested, regardless of the time of the cycle in which the stressor was
      applied. We did not observe a loss in body weight, but rather a smaller weight
      gain in stressed rats. Body weight gain was minimum in rats exposed to immersion
      and 6 hours of immobilization. Adrenal hypertrophy was observed in rats exposed
      to these same stressors. We conclude that: 1) the activation of the hypothalamus
      pituitary-adrenal axis by stress depends mainly on the characteristics of the
      stressor; 2) the response of this axis to stress also depends on the time of day
      in which the stressor is applied.

PMID- 12510014
TI  - Mutation research at ABCC/RERF: cytogenetic studies of atomic bomb exposed
      populations.

PMID- 12510015
TI  - Analysis of DNA and protein adducts of benzo[a]pyrene in human tissues using
      structure-specific methods.
AB  - We review studies which investigate the presence, using structure-specific
      analytical methods, of DNA or protein adducts of the carcinogen benzo[a]pyrene
      (BaP) in human tissues. The analytical methods include high performance liquid
      chromatography with fluorescence detection and gas chromatography-mass
      spectrometry. Although, for DNA detection these methods are somewhat less
      sensitive than non-specific techniques such as 32P-postlabeling and immunoassay,
      they have the distinct advantage of providing reliable structural information. In
      order to achieve adequate sensitivity, these methods often require the use of
      fairly large amounts of DNA (>100 microg) or protein (50-100mg). Most studies
      reviewed here measured tetraols released from DNA or protein by hydrolysis of
      adducts derived from (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene (BPDE), a major ultimate carcinogen of BaP. BPDE-DNA
      adducts were detected in 39% of 705 samples analyzed. BPDE-protein adducts were
      found in 59% of 772 samples. There was no single exposure situation that led to
      an overwhelming presence of detectable adducts. For example, BPDE-DNA adducts
      were detected in 45% of smokers, 33% of former smokers, 52% of non-smokers, 39%
      of occupationally exposed individuals, and 34% of environmentally exposed people.
      Adduct levels were influenced by polymorphisms in carcinogen metabolizing genes
      such as GSTM1, the presence of which was frequently protective. The relatively
      high occurrence of non-detectable adducts may result from low levels of BaP
      exposure and host factors such as genetic polymorphisms. Our analysis
      demonstrates that the presence of BaP adducts in human tissues cannot be assumed,
      even in situations where exposure to BaP is relatively high.

PMID- 12510016
TI  - Protein kinases and their involvement in the cellular responses to genotoxic
      stress.
AB  - Cells are constantly subjected to genotoxic stress, and much has been learned
      regarding their response to this type of stress during the past year. In general,
      the cellular genotoxic response can be thought to occur in three stages: (1)
      damage sensing; (2) activation of signal transduction pathways; (3) biological
      consequences and attenuation of the response. The biological consequences, in
      particular, include cell cycle arrest and cell death. Although our understanding
      of the molecular mechanisms underlying cellular genotoxic stress responses
      remains incomplete, many cellular components have been identified over the years,
      including a group of protein kinases that appears to play a major role. Various
      DNA-damaging agents can activate these protein kinases, triggering a protein
      phosphorylation cascade that leads to the activation of transcription factors,
      and altering gene expression. In this review, the involvement of protein kinases,
      particularly the mitogen-activated protein kinases (MAPKs), at different stages
      of the genotoxic response is discussed.

PMID- 12510017
TI  - Roles of DNA topoisomerases in chromosome segregation and mitosis.
AB  - DNA topoisomerases are highly specialized nuclear enzymes that perform
      topological changes in the DNA molecule in a very precise and unique fashion.
      Taking into account their fundamental roles in many events during DNA metabolism
      such as replication, transcription, recombination, condensation or segregation,
      it is no wonder that the last decade has witnessed an exponential interest on
      topoisomerases, mainly after the discovery of their potential role as targets in
      novel antitumor therapy. The difficulty of the lack of topoisomerase II mutants
      in higher eukaryotes has been partly overcome by the availability of drugs that
      act as either poisons or true catalytic inhibitors of the enzyme. These chemical
      tools have provided strong evidence that accurate performance of topoisomerase II
      is essential for chromosome segregation before anaphase, and this in turn
      constitutes a prerequisite for the development of normal mitosis. In the absence
      of cytokinesis, cells become polyploid or endoreduplicated.

PMID- 12510018
TI  - Coronary atherosclerosis and somatic mutations: an overview of the contributive
      factors for oxidative DNA damage.
AB  - Coronary artery disease (CAD) is a multifactorial process that appears to be
      caused by the interaction of environmental risk factors with multiple
      predisposing genes. Genetic research on CAD has traditionally focused on
      investigation aimed at identifying disease-susceptibility genes. Recent evidence
      suggests that somatically acquired DNA mutations may also contribute
      significantly to the pathogenesis of the disease, underlining the similarity
      between atherosclerotic and carcinogenic processes. The generation of oxidative
      stress has been emphasized as an important cause of DNA damage in
      atherosclerosis. This review highlights some of the major atherogenic risk
      factors as likely mediators in the oxidative modification of DNA. It also
      examines the hypothesis that an increase in oxidative stress may derive from
      "oxidatively" damaged mitochondria. Accordingly, further research in this field
      should be given high priority, since increased somatic DNA damage could be an
      important pathogenic factor and an additional prognostic predictor, as well as a
      potential target for therapeutic strategies in coronary artery disease.

PMID- 12510019
TI  - Effect of reactive cell density on net [2-14C]acetate uptake into rat brain:
      labeling of clusters containing GFAP+- and lectin+-immunoreactive cells.
AB  - Astrocytic proliferation is a hallmark of brain injury, but the biological
      functions and metabolic activities of reactive astrocytes in vivo are poorly
      understood. [2-14C]Acetate, which is preferentially transported into and,
      therefore, metabolized by astrocytes, was used to assess injury- and trophic
      factor-induced changes in astrocyte metabolic activity. Local rates of net [2
      14C]acetate uptake and glucose utilization (CMR(glc)), determined with
      [14C]deoxyglucose to assay overall metabolic activity of all brain cells, were
      assayed 7 days after a cannula placement; adjacent brain sections were
      immunostained to identify glial fibrillary acidic protein-positive (GFAP(+))
      astrocytes and microglia plus macrophages (lectin-positive cells). GFAP(+) cells
      were abundant in tissue surrounding the cannula compared to the contralateral
      hemisphere, whereas lectin(+) cells were restricted to the wound boundary.
      CMR(glc) fell 25% in regions enriched in reactive astrocytes compared to the
      homologous contralateral hemisphere, whereas [14C]acetate uptake increased
      slightly (6%) but statistically significantly; metabolism of both tracers in 13
      other brain structures was unchanged. Injection of basic fibroblast growth factor
      (b-FGF) into cerebral cortex or superior colliculus produced fiber-rich cell
      clusters containing both GFAP(+) and lectin(+) cells that had a 37% increase in
      [14C]acetate uptake; GFAP(+)-cell density rose in the nearby neuropil but the
      corresponding change in [14C]acetate uptake was small (6-8%). Sensory stimulation
      did not alter [14C]acetate uptake into the clusters. Thus, [14C]acetate uptake
      was relatively stable with respect to changes in the density of reactive
      astrocytes that are dispersed throughout the neuropil and to changes in cellular
      activity arising from sensory stimulation. In contrast, b-FGF-induced cell
      clusters that contain mixed cell types and numerous fibers accumulated higher
      levels of [14C]acetate, raising the possibility that increased uptake might be
      due to high numbers of activated astrocytes and, perhaps, acetate metabolism by
      other cell types.

PMID- 12510020
TI  - SM-31900, a novel NMDA receptor glycine-binding site antagonist, reduces infarct
      volume induced by permanent middle cerebral artery occlusion in spontaneously
      hypertensive rats.
AB  - The purpose of this study was to investigate the effect of (3S)-7-chloro-3-[2
      ((1R)-1-carboxyethoxy)-4-aminomethylphenyl]aminocarbonylmethyl-1,3,4,5
      tetrahydrobenz[c,d]indole-2-carboxylic acid hydrochloride (SM-31900), an
      antagonist with high selectivity and affinity for the NMDA receptor glycine
      binding site, on the cerebral infarct volume in a permanent middle cerebral
      artery occlusion (MCAo) model, which was constructed by electrocoagulation of a
      unilateral middle cerebral artery distal to the olfactory tract using
      spontaneously hypertensive rats (SHRs). To investigate the dose-response
      characteristics and the therapeutic time window of SM-31900 in this MCAo model,
      we conducted three experiments, in which the administration of SM-31900 was
      started 5min (experiment I), 30min (experiment II), or 60min (experiment III)
      after MCAo, respectively. In all the studies, SM-31900 was administered by
      intravenous bolus injection followed by continuous intravenous infusion to obtain
      a steady-state level of this compound in blood immediately after its
      administration. The treatment with SM-31900 was continued until 24h after MCAo,
      at which time the cerebral infarct volume was measured. In experiment I, SM-31900
      significantly reduced the infarct volume by 37% at a dosage of 0.38mg/kg bolus
      followed by 1.5mg/kg/h continuous infusion (0.38mg/kg+1.5mg/kg/h). In experiment
      II, the neuroprotective effect of SM-31900 was also significant, with a 25%
      reduction in infarct volume at a dosage of 0.38mg/kg+1.5mg/kg/h, and a 40%
      reduction at 1.5mg/kg+6.0mg/kg/h. Furthermore, even in experiment III, SM-31900
      exerted a significant neuroprotective effect, with a 20% reduction at
      1.5mg/kg+6.0mg/kg/h. These studies revealed that SM-31900 can exert a
      neuroprotective effect when it is administered up to at least 60min after the
      onset of ischemia in the MCAo model, an animal model of stroke, indicating that
      SM-31900 is a good candidate for treating acute brain ischemia.

PMID- 12510021
TI  - WR-2721 (amifostine, ethyol) prevents motor and morphological changes induced by
      neonatal X-irradiation.
AB  - Neonatal X-irradiation induces permanent abnormalities in cerebellar cortex
      cytoarchitecture and neurochemistry, as well as impairment in motor gait. The aim
      of the present work was to examine the potential protective properties of WR-2721
      (Amifostine, Ethyol), a free radical scavenger, against the above mentioned
      alterations by using a previously described neuroprotection assessment protocol.
      Pre-irradiation treatment with amifostine was effective in partially preventing
      the cerebellar morphological damage and the motor gait impairment induced by
      ionizing radiation. No changes in cerebellar noradrenaline (NA) levels were
      detected in amifostine-treated irradiated animals. These results suggest that it
      is possible to counteract radiation-induced damage in the cerebella and motor
      gait of neonatal rats through oxygen free radical scavenger administration prior
      to irradiation. The presence of the agent before the injury occurs, favors the
      efficacy of amifostine neuroprotective activity. Clinical implications of this
      model are related to the daily exposure of many people to different sources of
      radiation (accidental, diagnostical or therapeutical).

PMID- 12510022
TI  - Endogenous glutamate contributes to the maintenance of glutathione level under
      oxidative stress in isolated nerve terminals.
AB  - Exposure of isolated nerve terminals to hydrogen peroxide (25-500 microM) for 10
      min produced a partially reversible decrease in the total and reduced glutathione
      level. No release and resynthesis of glutathione by the oxidant was involved in
      this effect. Loss of reduced glutathione was associated with elimination of
      H(2)O(2), which was very quick with >70% of the oxidant eliminated within 5 min.
      Recovery of both total and reduced glutathione was pronounced after 10 min when
      the majority of H(2)O(2) was eliminated. Previously we have reported that
      glutamate metabolism under oxidative stress contributes to the operation of the
      Krebs cycle, thus to the production of NAD(P)H [J. Neurosci. 20 (2000) 8972]. In
      the present study we addressed whether metabolism of endogenous glutamate plays a
      role in the maintenance of glutathione level in nerve terminals. Glutamine and
      beta-hydroxybutyrate (5mM), alternative metabolites in synaptosomes, were able to
      decrease the loss of total and reduced glutathione induced by hydrogen peroxide.
      Metabolic consumption of glutamate was reduced at the same time. In addition an
      increased demand on the glutathione system by the catalase inhibitor
      aminotriazole augmented the metabolic consumption of glutamate. It is concluded
      that under oxidative stress glutamate metabolism contributes to the maintenance
      of glutathione level, thus to the antioxidant capacity of nerve terminals.

PMID- 12510023
TI  - Neurosteroid-induced hyperalgesia through a histamine release is inhibited by
      progesterone and p,p'-DDE, an endocrine disrupting chemical.
AB  - The intraplantar injection of dehydroepiandrosterone sulfate (DHEAS), a
      representative neurosteroid, showed hyperalgesia in the Hargreaves' thermal or
      automatic paw-pressure mechanical nociception test. The DHEAS-induced
      hyperalgesia was abolished by diphenhydramine (DPH), a H(1) histamine (His)
      receptor antagonist, as well as the hyperalgesia induced by His or compound
      48/80, a mast cell degranulating agent. The DHEAS-induced hyperalgesia was also
      blocked by progesterone (PROG), another type of neurosteroid and a putative
      neurosteroid receptor antagonist. Neither DPH nor PROG showed any changes in the
      thermal threshold. On the other hand, endocrine disrupting chemicals (EDCs) are
      known to disrupt reproductive system in wild-lives and humans through the
      disturbance of the endocrine homeostasis. In this study, the flexor responses
      induced by intraplantar injection of DHEAS were blocked by p,p'-DDE, an EDC as
      well as by PROG in the algogenics-induced nociceptive flexor responses test (ANF
      test) in mice. Similarly, p,p'-DDE blocked the DHEAS-induced hyperalgesia in
      Hargreaves' thermal nociception test. Besides the hyperalgesic actions, DHEAS
      increased vascular permeability as measured with Evans blue plasma extravasation.
      Consistent with behavioral studies, it was blocked by DPH, PROG, and p,p'-DDE.
      These results suggest that DHEAS has significant hyperalgesic and vasodilatory
      actions through histamine release, and these actions were reversible by PROG and
      an EDC.

PMID- 12510024
TI  - Effect of amphetamine and phencyclidine on DNA-binding activities of serum
      response and dyad symmetry elements.
AB  - Acute administration of D-amphetamine sulphate (AMPH) and (1-[1
      phenylcyclohexyl]piperidine hydrochloride) (phencyclidine; PCP) produces a
      characteristic spatio-temporal distribution of c-Fos protein in the brain. As
      transcriptional mechanisms underlying the induction of c-fos gene expression may
      be regulated in a stimulus-specific manner, we have analyzed the binding
      activities of serum response element (SRE), dyad symmetry element (DSE) and
      calcium response element (CRE), the major regulatory sites of the c-fos promoter.
      Electrophoretic mobility shift showed that SRE binding activity was increased for
      50-60%, 2-6h after AMPH, while treatment with PCP resulted in light decrease of
      SRE binding activity throughout the same time period. Co-administration of AMPH
      and PCP induced gradual increase of SRE binding activity, reaching maximum (86%)
      at 6h. Binding of nuclear proteins to DSE sequence was increased 1-2h after
      administration of AMPH (72-87%) and remained elevated till the end of the time
      window observed. PCP and AMPH/PCP caused different temporal profile of DSE
      binding with peak (40-54%) 4-6h after administration. In contrast, DNA-binding
      activity of the CRE sequences remained unchanged throughout the time period of 6h
      under all conditions. Finally, supershift analysis clearly demonstrated presence
      of SRF and c-Fos protein in the transcriptional complexes bound to SRE and DSE
      sequences irrespective to AMPH, PCP or combined treatment. These findings also
      showed that the presence of c-Fos protein in SRE and DSE nucleocomplex support
      the hypothesis concerning autoregulation of c-fos gene expression during
      psychostimulant action in vivo.

PMID- 12510025
TI  - Effect of trans-resveratrol on signal transduction pathways involved in
      paclitaxel-induced apoptosis in human neuroblastoma SH-SY5Y cells.
AB  - trans-Resveratrol (3,4',5-trihydroxystilbene) is able to significantly reduce
      paclitaxel-induced apoptosis in the human neuroblastoma (HN) SH-SY5Y cell line,
      acting on several cellular signaling pathways that are involved in paclitaxel
      induced apoptosis. trans-Resveratrol reverses phosphorylation of Bcl-2 induced by
      paclitaxel and concomitantly blocks Raf-1 phosphorylation, also observed after
      paclitaxel exposure, thus suggesting that Bcl-2 inactivation may be dependent on
      the activation of the Raf/Ras cascade. trans-Resveratrol also reverses the
      sustained phosphorylation of JNK/SAPK, which specifically occurs after paclitaxel
      exposure.Overall, our observations demonstrate that (a) the toxic action of
      paclitaxel on neuronal-like cells is not only related to the effect of the drug
      on tubulin, but also to its capacity to activate several intracellular pathways
      leading to inactivation of Bcl-2, thus causing cells to die by apoptosis, (b)
      trans-resveratrol significantly reduces paclitaxel-induced apoptosis by
      modulating the cellular signaling pathways which commit the cell to apoptosis.

PMID- 12510026
TI  - Dopaminergic neurons develop axonal projections to their target areas in
      organotypic co-cultures of the ventral mesencephalon and the striatum/prefrontal
      cortex.
AB  - Mesencephalic dopaminergic neurons are known to project to the prefrontal cortex
      (PFC) and the striatum (STR). Organotypic slice co-cultures of the ventral
      tegmental area/substantia nigra (VTA/SN)-complex and the PFC or STR,
      respectively, were used to analyze the cytoarchitectural organization of the
      VTA/SN-complex and the innervation pattern of the target slices by dopaminergic
      fibers. After 10-28 days of culturing immunocytochemistry with antibodies against
      tyrosine hydroxylase (TH) was performed. The VTA/SN-complex revealed in vitro an
      organization of TH-positive cells similar to those observed in rat brains of
      comparable age. TH-immunoreactive cells exhibited their typical morphology and
      formed long processes. No TH-immunolabeled elements were found in single cultures
      of PFC and STR. Tracing of VTA/SN fibers with biocytin as well as TH
      immunostaining showed numerous labeled fibers in the co-cultured slices.
      Extensive fiber crossing was observed in the co-cultures of the VTA/SN-complex
      and STR but only a sparse fiber bridge in the co-cultured slices of VTA/SN
      complex and PFC. The VTA/SN-complex-PFC system obviously retained several of its
      in vivo characteristics, e.g. the fiber network in the prefrontal cortical
      subareas. Our results demonstrate that TH-immunoreactive neurons develop their
      typical innervation pattern in slice co-cultures of VTA/SN-complex and PFC or
      STR, respectively. This in vitro approach may be useful for investigations of the
      dopaminergic function in the VTA/SN-prefrontal pathway.

PMID- 12510027
TI  - The field of child maltreatment enters its fifth decade.

PMID- 12510028
TI  - Social information processing in high-risk and physically abusive parents.

PMID- 12510029
TI  - Attributions, affect, and behavior in abuse-risk mothers: a laboratory study.
AB  - OBJECTIVE: There were two main aims: first, to assess parental attributions about
      child behavior in abuse-risk and nonclinic parents. Second, to assess how
      attributions predict affective and behavioral reactions to child behavior.
      METHOD: Internal-external attributions relating to the causes of child behavior
      were compared across mothers at-risk of child abuse (n = 40) and mothers who
      reported no significant parental or child conduct or behavior problems (n = 20).
      Mothers' attributions about the causes of the behavior of their own child and an
      unfamiliar child were recorded in response to the presentation of videotaped
      excerpts of the behavior. RESULTS: Results highlighted that compared with
      nonclinic mothers, abuse-risk mothers had a tendency to attribute positive child
      behavior to more external causes and negative child behavior to more internal
      causes. Differences were also found between parental cognitions about clearly
      positive, clearly naughty, and ambiguous child behavior. In the abuse-risk group,
      positive child behavior predicted coercive parenting when it elicited angry
      feelings in the mother; ambiguous and naughty child behavior led to coercive
      parenting through valence ratings of "deviant" and attributions of "internality."
      Analyses within the abuse-risk group showed that parental attributions are
      predictive of parental coerciveness for unfamiliar behavior. As behavior becomes
      more familiar, ratings of its valence and the affect it elicits override
      attributional activity. CONCLUSIONS: Parental attributions about the causes of
      child behavior differ according to the valence and familiarity of that behavior,
      and discriminate between parents at risk for child abuse. Further, attributions
      are predictive of the affective and behavioral responses the parent makes to the
      child's behavior for ambiguous or unfamiliar behavior. Evidence was found for the
      validity of using videotaped stimuli of the behavior of known and unknown
      children as a method of assessing parental attributions.

PMID- 12510030
TI  - To a safer place? Victims of sexual abuse by females and their disclosures to
      professionals.
AB  - OBJECTIVE: To explore the experiences of victims of female sex offenders with
      regard to disclosing sexual abuse to a professional, and importantly, the impact
      of professional responses on victims. METHOD: The data were derived from one-to
      one semi-structured interviews with 14 (7 males, 7 females) victims of child
      sexual abuse by female perpetrators. Victims ranged in age from 23 to 59 years
      and were recruited through professional referrals or through poster
      advertisements in counseling services. Participants responded to questions on
      their family background, experience(s) of sexual abuse, experience(s) disclosing
      the sexual abuse to a professional, and the impact of professional responses.
      RESULTS: The majority of victims reported sexual abuse by their mothers. The
      average age of onset of the sexual abuse was age 5, lasting, on average, 6 years.
      Five participants reported experiencing severe, moderate and mild sexual abuse,
      four reported experiencing both severe and mild sexual abuse and five reported
      experiencing moderate and mild sexual abuse. The findings underscore the
      significance of professional intervention in relation to victim disclosures of
      sexual abuse by females. Professional responses to disclosures, whether positive
      or negative, appeared to have a crucial impact on the well-being of victims.
      Supportive professional responses including the acknowledgment and validation of
      victims' experiences of sexual abuse appeared to mitigate the negative effects of
      the abuse. In contrast, unsupportive responses where professionals minimized, or
      disbelieved victims' allegations of sexual abuse appeared to exacerbate the
      negative effects of the sexual abuse, ultimately inciting secondary
      victimization. CONCLUSION: The study highlights the need for the development and
      implementation of professional training initiatives to sensitize professionals to
      the issue of female sex offending and the intervention needs of victims. Failure
      to do so could have negative consequences for victims sexually abused by females.

PMID- 12510031
TI  - Psychological correlates of physical abuse in Hong Kong Chinese adolescents.
AB  - OBJECTIVE: To understand the associations between adolescent family physical
      maltreatment and psychiatric morbidity or psychological problems. METHODS:
      questionnaire survey on 489 secondary school students in Form 2 from 10 schools
      in Hong Kong. Questions regarding three forms of family physical maltreatment
      were measured: corporal punishment within the past 6 months, beaten without any
      reason within the past 6 months, or ever been beaten to injury. MAIN RESULT:
      Corporal punishment was not associated with the psychological variables after
      Bonferroni adjustment was made. Those who experienced the two other forms of
      physical maltreatment had significant and strong associations with positive
      Achenbach CBCL outcome (OR from 3.26 to 3.27), drug abuse problems (OR from 2.60
      to 20.38), self-injurious behaviors (OR from 3.34 to 8.47) and poor perceived
      parental support. In addition, those who had ever been beaten to injury scored
      significantly lower in the "physical appearance" and "behavioral conduct"
      subscales of the Harter's Self-Perception Profile for Adolescents. CONCLUSIONS:
      In Hong Kong, some forms of family physical maltreatment (beaten for no reason
      and beaten to injury) were associated with a number of psychiatric/psychological
      problems. Further studies should be carried out to clarify whether the
      relationships are causal in nature.

PMID- 12510032
TI  - Improving data systems about juvenile victimization in the United States.
AB  - OBJECTIVE: To suggest improvements to 13 data sets and systems that collect
      information about juvenile victimization in United States. METHOD: The
      suggestions were gathered from a variety of sources, including data system users
      and administrators, as well as a special meeting convened on the topic by the
      National Consortium on Children, Families and the Law in Washington, DC (December
      2000). RESULTS: Key areas of improvement were identified for each of 13 US data
      systems and possible solutions were identified. CONCLUSIONS: This paper suggests
      three broad categories of improvements that apply to a number of data systems.
      First, data systems could expand the coverage of the systems to include more
      jurisdictions or other segments of the population. Second, in order to be more
      comprehensive and specific to child victimization, the systems need to create
      more specific data items, questions, or response categories. Finally, the data
      systems need to be modified to provide continuity and interrelationships among
      systems, either by using uniform definitions, or integrating data systems to
      facilitate the tracking of children across systems.

PMID- 12510033
TI  - Catch-up growth assessment in long-term physically neglected and emotionally
      abused preschool age male children.
AB  - OBJECTIVE: To assess the catch-up growth of long-term physically neglected and
      emotionally abused preschool male children who have entered foster residential
      care and remained 1 year after initial placement. METHOD: Longitudinal study over
      a 7-year period (1994-2001). So that a child was eligible for the study, three
      selection criteria were included: (1) aged between 24 and 48 months at the time
      of entry into residential facility, (2) having suffered both long-term (more than
      6 months) physically neglected and emotionally abused, and (3) having stayed in
      foster care for 1 year after initial placement. Weight, height, and head
      circumference were established upon entry and re-assessed 1 year after initial
      placement, calculating the annual growth velocity. Results were compared with
      normal regional longitudinal standards of reference (Z score). Student's t test
      was used to assess statistically significant differences. RESULTS: During the
      study period, 87 children aged between 24 and 48 months (54 male/33 female) were
      admitted to residential facility after having suffered both long-term physical
      neglect and emotional abuse. Nevertheless, only 20 children (23% of the total
      admissions) met the third selection criteria (having remained 1 year after
      initial placement). Of these children, all were males and at placement they were
      between the ages of 30 and 42 months, with an average age of 36 months (1.9 SD).
      At placement, the analyzed parameters were below the normal standards, showing a
      statistically significant difference for height (Z score = -1.29; p = .008) and
      weight (Z score = -.75; p = .038). The annual growth velocity for all parameters
      was above the normal standards showing a statistically significant difference for
      height (Z score = +1.43; p = .009). One year after initial placement, the
      significant differences for height (Z score = -.68; p = .102) and weight (Z score
      = -.31; p = .435) with respect to the normal standards disappeared, though still
      remained below, showing a significant catch-up growth for height (improvement
      height Z = +.61 SD). CONCLUSIONS: At placement, the both long-term physically
      neglected and emotionally abused preschool age male children showed a mild form
      of chronic malnutrition with growth failure. Growth failure was reversible after
      the first year of stay, which demonstrates that this delay in growth was
      secondary to nutritional and psychosocial factors. Placement in foster
      residential care was beneficial for the catch-up growth of these patients.

PMID- 12510034
TI  - Cultural norms versus state law in treating incest: a suggested model for Arab
      families.
AB  - OBJECTIVE: This article examines problems of intervention in sexual abuse cases
      among collective societies and offers a culturally sensitive model of
      intervention. METHOD: The manuscript is based on cross-cultural literature and
      clinical cases within the Palestinian community in Israel. RESULTS: Unlike
      Western societies in which the state takes responsibility for the needs of its
      citizens and has laws that aim to protect victims of sexual abuse and to punish
      the perpetrators, in many collective societies people live in interdependence
      with their families. The family, rather than the state, is the main provider and
      protector. Enforcing the laws against sexual perpetrators, typically, threatens
      the unity and reputation of the family, and therefore this option is rejected and
      the family turns against the victim. Instead of punishing the perpetrator,
      families often protect him and blame the victim for the resulting mess. The
      punishment of the abuser results in the re-victimization of the abused since the
      family possesses supreme authority. We suggest a culturally sensitive model of
      intervention that includes six stages: (1) verification of information, (2)
      mapping the family, (3) bonding with progressive forces, (4) a condemning,
      apologizing, and punishing ceremony, (5) treatment, and (6) follow-up.
      CONCLUSION: Culturally sensitive intervention that exploits the power of the
      family for the benefit of the victim of abuse before enforcing the law, may
      achieve the same legal objectives as state intervention, without threatening the
      reputation and the unity of the family, and may therefore save the victim from
      harm.

PMID- 12510035
TI  - Homicidal commotio cordis: the final blow in a battered infant.
AB  - OBJECTIVE: This report describes in detail the occurrence of inflicted commotio
      cordis (cardiac concussion) in a previously abused 7-week-old. Though inflicted
      commotio cordis has been reported in three toddlers, this is the first report in
      a young infant. METHOD: Following documentation of abuse in a living child, the
      case of a death of a prior sibling--previously regarded as natural--was re-opened
      for further investigation. Original autopsy materials were reviewed, and the body
      of the deceased child was exhumed. RESULTS: Exhumation and second autopsy
      documented more than 50 fractures in the deceased child. When re-interviewed, the
      children's father admitted to causing the injuries in both children, and gave a
      textbook description of commotio cordis as the mechanism of death in the fatal
      case. CONCLUSIONS: Commotio cordis is a rare event in which a fatal dysrhythmia-
      usually ventricular fibrillation--is precipitated by a blow to the precordial
      chest. Previous reports have indicated that homicidal commotio cordis can occur
      in small children. This report demonstrates that commotio cordis can occur even
      in the very young, previously abused infant.

PMID- 12510036
TI  - Hallervorden and history.

PMID- 12510037
TI  - A randomized, controlled trial of the use of pulmonary-artery catheters in high
      risk surgical patients.
AB  - BACKGROUND: Some observational studies suggest that the use of pulmonary-artery
      catheters to guide therapy is associated with increased mortality. METHODS: We
      performed a randomized trial comparing goal-directed therapy guided by a
      pulmonary-artery catheter with standard care without the use of a pulmonary
      artery catheter. The subjects were high-risk patients 60 years of age or older,
      with American Society of Anesthesiologists (ASA) class III or IV risk, who were
      scheduled for urgent or elective major surgery, followed by a stay in an
      intensive care unit. Outcomes were adjudicated by observers who were unaware of
      the treatment-group assignments. The primary outcome was in-hospital mortality
      from any cause. RESULTS: Of 3803 eligible patients, 1994 (52.4 percent) underwent
      randomization. The base-line characteristics of the two treatment groups were
      similar. A total of 77 of 997 patients who underwent surgery without the use of a
      pulmonary-artery catheter (7.7 percent) died in the hospital, as compared with 78
      of 997 patients in whom a pulmonary-artery catheter was used (7.8 percent)--a
      difference of 0.1 percentage point (95 percent confidence interval, -2.3 to 2.5).
      There was a higher rate of pulmonary embolism in the catheter group than in the
      standard-care group (8 events vs. 0 events, P=0.004). The survival rates at 6
      months among patients in the standard-care and catheter groups were 88.1 and 87.4
      percent, respectively (difference, -0.7 percentage point [95 percent confidence
      interval, -3.6 to 2.2]; negative survival differences favor standard care); at 12
      months, the rates were 83.9 and 83.0 percent, respectively (difference, -0.9
      percentage point [95 percent confidence interval, -4.3 to 2.4]). The median
      hospital stay was 10 days in each group. CONCLUSIONS: We found no benefit to
      therapy directed by pulmonary-artery catheter over standard care in elderly, high
      risk surgical patients requiring intensive care.

PMID- 12510038
TI  - A controlled trial of natalizumab for relapsing multiple sclerosis.
AB  - BACKGROUND: In patients with multiple sclerosis, inflammatory brain lesions
      appear to arise from autoimmune responses involving activated lymphocytes and
      monocytes. The glycoprotein alpha4 integrin is expressed on the surface of these
      cells and plays a critical part in their adhesion to the vascular endothelium and
      migration into the parenchyma. Natalizumab is an alpha4 integrin antagonist that
      reduced the development of brain lesions in experimental models and in a
      preliminary study of patients with multiple sclerosis. METHODS: In a randomized,
      double-blind trial, we randomly assigned a total of 213 patients with relapsing
      remitting or relapsing secondary progressive multiple sclerosis to receive 3 mg
      of intravenous natalizumab per kilogram of body weight (68 patients), 6 mg per
      kilogram (74 patients), or placebo (71 patients) every 28 days for 6 months. The
      primary end point was the number of new brain lesions on monthly gadolinium
      enhanced magnetic resonance imaging during the six-month treatment period.
      Clinical outcomes included relapses and self-reported well-being. RESULTS: There
      were marked reductions in the mean number of new lesions in both natalizumab
      groups: 9.6 per patient in the placebo group, as compared with 0.7 in the group
      given 3 mg of natalizumab per kilogram (P<0.001) and 1.1 in the group given 6 mg
      of natalizumab per kilogram (P<0.001). Twenty-seven patients in the placebo group
      had relapses, as compared with 13 in the group given 3 mg of natalizumab per
      kilogram (P=0.02) and 14 in the group given 6 mg of natalizumab per kilogram
      (P=0.02). The placebo group reported a slight worsening in well-being (a mean
      decrease of 1.38 mm on a 100-mm visual-analogue scale), whereas the natalizumab
      groups reported an improvement (mean increase of 9.49 mm in the group given 3 mg
      of natalizumab per kilogram and 6.21 mm in the group given 6 mg of natalizumab
      per kilogram). CONCLUSIONS: In a placebo-controlled trial, treatment with
      natalizumab led to fewer inflammatory brain lesions and fewer relapses over a six
      month period in patients with relapsing multiple sclerosis.

PMID- 12510039
TI  - Natalizumab for active Crohn's disease.
AB  - BACKGROUND: In chronic inflammatory conditions such as Crohn's disease, the
      migration of leukocytes from the circulation into the parenchyma and their
      activation within inflammatory sites are mediated in part by alpha4 integrins.
      METHODS: We conducted a double-blind, placebo-controlled trial of the alpha4
      integrin-specific humanized monoclonal antibody natalizumab in 248 patients with
      moderate-to-severe Crohn's disease. Patients were randomly assigned to receive
      one of four treatments: two infusions of placebo; one infusion of 3 mg of
      natalizumab per kilogram of body weight, followed by placebo; two infusions of 3
      mg of natalizumab per kilogram; or two infusions of 6 mg of natalizumab per
      kilogram. Infusions were given four weeks apart. Outcomes included changes in
      scores for the Crohn's Disease Activity Index (higher scores indicate more severe
      disease), the health-related quality of life, and C-reactive protein levels.
      RESULTS: The group given two infusions of 6 mg of natalizumab per kilogram did
      not have a significantly higher rate of clinical remission (defined by a score of
      less than 150 on the Crohn's Disease Activity Index) than the placebo group at
      week 6 (the prospectively defined primary end point in the efficacy analysis).
      However, both groups that received two infusions of natalizumab had higher
      remission rates than the placebo group at multiple time points. Natalizumab also
      produced a significant improvement in response rates (defined by a reduction of
      at least 70 points in the score on the Crohn's Disease Activity Index). The
      highest remission rate was 44 percent and the highest response rate was 71
      percent (at week 6 in the group given two infusions of 3 mg per kilogram).
      Overall, the two infusions of 6 mg of natalizumab per kilogram and of 3 mg per
      kilogram had similar effects. The quality of life improved in all natalizumab
      groups; C-reactive protein levels improved in groups receiving two infusions of
      natalizumab. The rates of adverse events were similar in all four groups.
      CONCLUSIONS: Treatment with the selective adhesion-molecule inhibitor natalizumab
      increased the rates of clinical remission and response, improved the quality of
      life and C-reactive protein levels, and was well tolerated in patients with
      active Crohn's disease.

PMID- 12510040
TI  - Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.
AB  - BACKGROUND: Hallervorden-Spatz syndrome is an autosomal recessive disorder
      characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many
      patients with this disease have mutations in the gene encoding pantothenate
      kinase 2 (PANK2); these patients are said to have pantothenate kinase-associated
      neurodegeneration. In this study, we compared the clinical and radiographic
      features of patients with Hallervorden-Spatz syndrome with and without mutations
      in PANK2. METHODS: One hundred twenty-three patients from 98 families with a
      diagnosis of Hallervorden-Spatz syndrome were classified on the basis of clinical
      assessment as having classic disease (characterized by early onset with rapid
      progression) or atypical disease (later onset with slow progression). Their
      genomic DNA was sequenced for PANK2 mutations. RESULTS: All patients with classic
      Hallervorden-Spatz syndrome and one third of those with atypical disease had
      PANK2 mutations. Whereas almost all mutations in patients with atypical disease
      led to amino acid changes, those in patients with classic disease more often
      resulted in predicted protein truncation. Patients with atypical disease who had
      PANK2 mutations were more likely to have prominent speech-related and psychiatric
      symptoms than patients with classic disease or mutation-negative patients with
      atypical disease. In all patients with pantothenate kinase-associated
      neurodegeneration, whether classic or atypical, T2-weighted magnetic resonance
      imaging (MRI) of the brain showed a specific pattern of hyperintensity within the
      hypointense medial globus pallidus. This pattern was not seen in any patients
      without mutations. CONCLUSIONS: PANK2 mutations are associated with all cases of
      classic Hallervorden-Spatz syndrome and one third of cases of atypical disease. A
      specific MRI pattern distinguishes patients with PANK2 mutations. Predicted
      levels of pantothenate kinase 2 protein correlate with the severity of disease.

PMID- 12510042
TI  - Clinical practice. Preventing falls in elderly persons.

PMID- 12510043
TI  - Population screening in the age of genomic medicine.

PMID- 12510044
TI  - Clinical problem-solving. Easy to see but hard to find.

PMID- 12510046
TI  - Progress in research on pulmonary-artery catheters.

PMID- 12510047
TI  - Alpha4 integrins as therapeutic targets in autoimmune disease.

PMID- 12510048
TI  - Cough and bronchial responsiveness in firefighters at the World Trade Center
      site.

PMID- 12510049
TI  - Exercise and the prevention of cardiovascular events in women.

PMID- 12510050
TI  - IgA nephropathy.

PMID- 12510051
TI  - Office-based treatment of opioid-dependent patients.

PMID- 12510052
TI  - Switching emergency contraception to over-the-counter status.

PMID- 12510053
TI  - Ancient clinical trials.

PMID- 12510054
TI  - Pulmonary alveolar microlithiasis revisited.

PMID- 12510055
TI  - Methemoglobinemia and topical pharyngeal anesthesia.

PMID- 12510056
TI  - Linezolid-induced lactic acidosis.

PMID- 12510057
TI  - Images in clinical medicine. Pulmonary-artery aneurysm.

PMID- 12510058
TI  - Insulin resistance of glycogen synthase mediated by o-linked N-acetylglucosamine.
AB  - We have investigated the mechanism by which high concentrations of glucose
      inhibit insulin stimulation of glycogen synthase. In NIH-3T3-L1 adipocytes
      cultured in low glucose (LG; 2.5 mm), the half-maximal activation concentration
      (A(0.5)) of glucose 6-phosphate was 162 +/- 15 microm. Exposure to either high
      glucose (HG; 20 mm) or glucosamine (GlcN; 10 mm) increased the A(0.5) to 558 +/-
      61 or 612 +/- 34 microm. Insulin treatment with LG reduced the A(0.5) to 96 +/-
      10 microm, but cells cultured with HG or GlcN were insulin-resistant (A(0.5) =
      287 +/- 27 or 561 +/- 77 microm). Insulin resistance was not explained by
      increased phosphorylation of synthase. In fact, culture with GlcN decreased
      phosphorylation to 61% of the levels seen in cells cultured in LG. Hexosamine
      flux and subsequent enzymatic protein O-glycosylation have been postulated to
      mediate nutrient sensing and insulin resistance. Glycogen synthase is modified by
      O-linked N-acetylglucosamine, and the level of glycosylation increased in cells
      treated with HG or GlcN. Treatment of synthase in vitro with protein phosphatase
      1 increased basal synthase activity from cells cultured in LG to 54% of total
      activity but was less effective with synthase from cells cultured in HG or GlcN,
      increasing basal activity to only 13 or 16%. After enzymatic removal of O-GlcNAc,
      however, subsequent digestion with phosphatase increased basal activity to over
      73% for LG, HG, and GlcN. We conclude that O-GlcNAc modification of glycogen
      synthase results in the retention of the enzyme in a glucose 6-phosphate
      dependent state and contributes to the reduced activation of the enzyme in
      insulin resistance.

PMID- 12510059
TI  - Modulation of insulin-stimulated degradation of human insulin receptor substrate
      1 by Serine 312 phosphorylation.
AB  - Ser/Thr phosphorylation of insulin receptor substrate-1 (IRS-1) is a negative
      regulator of insulin signaling. One potential mechanism for this is that Ser/Thr
      phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by
      the insulin receptor. An additional mechanism for modulating insulin signaling is
      via the down-regulation of IRS-1 protein levels. Insulin-induced degradation of
      IRS-1 has been well documented, both in cells as well as in patients with
      diabetes. Ser/Thr phosphorylation of IRS-1 correlates with IRS-1 degradation, yet
      the details of how this occurs are still unknown. In the present study we have
      examined the potential role of different signaling cascades in the insulin
      induced degradation of IRS-1. First, we found that inhibitors of the
      phosphatidylinositol 3-kinase and mammalian target of rapamycin block the
      degradation. Second, knockout cells lacking one of the key effectors of this
      cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in
      the insulin-stimulated degradation of IRS-1. Conversely, overexpression of this
      enzyme potentiated insulin-stimulated IRS-1 degradation. Third, concurrent with
      the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3
      kinase and mammalian target of rapamycin also blocked the insulin-stimulated
      increase in Ser(312) phosphorylation. Most important, an IRS-1 mutant in which
      Ser(312) was changed to alanine was found to be resistant to insulin-stimulated
      IRS-1 degradation. Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at
      10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet
      completely blocked insulin-stimulated c-Jun phosphorylation. Further, insulin
      stimulated c-Jun phosphorylation was not blocked by inhibitors of the
      phosphatidylinositol 3-kinase and mammalian target of rapamycin, indicating that
      c-Jun N-terminal kinase is unlikely to be the kinase phosphorylating IRS-1
      Ser(312) in response to insulin. In summary, our results indicate that the
      insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase
      pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1.

PMID- 12510060
TI  - Insulin secretory deficiency and glucose intolerance in Rab3A null mice.
AB  - Insulin secretory dysfunction of the pancreatic beta-cell in type-2 diabetes is
      thought to be due to defective nutrient sensing and/or deficiencies in the
      mechanism of insulin exocytosis. Previous studies have indicated that the GTP
      binding protein, Rab3A, plays a mechanistic role in insulin exocytosis. Here, we
      report that Rab3A(-/-) mice develop fasting hyperglycemia and upon a glucose
      challenge show significant glucose intolerance coupled to ablated first-phase
      insulin release and consequential insufficient insulin secretion in vivo, without
      insulin resistance. The in vivo insulin secretory response to arginine was
      similar in Rab3A(-/-) mice as Rab3A(+/+) control animals, indicating a phenotype
      reminiscent of insulin secretory dysfunction found in type-2 diabetes. However,
      when a second arginine dose was given 10 min after, there was a negligible
      insulin secretory response in Rab3A(-/-) mice, compared with that in Rab3A(+/+)
      animals, that was markedly increased above that to the first arginine stimulus.
      There was no difference in beta-cell mass or insulin production between Rab3A(-/
      ) and Rab3A(+/+) mice. However, in isolated islets, secretagogue-induced insulin
      release (by glucose, GLP-1, glyburide, or fatty acid) was approximately 60-70%
      lower in Rab3A(-/-) islets compared with Rab3A(+/+) controls. Nonetheless, there
      was a similar rate of glucose oxidation and glucose-induced rise in cytosolic
      [Ca(2+)](i) flux between Rab3A(-/-) and Rab3A(+/+) islet beta-cells, indicating
      the mechanistic role of Rab3A lies downstream of generating secondary signals
      that trigger insulin release, at the level of secretory granule transport and/or
      exocytosis. Thus, Rab3A plays an important in vivo role facilitating the
      efficiency of insulin exocytosis, most likely at the level of replenishing the
      ready releasable pool of beta-granules. Also, this study indicates, for the first
      time, that the in vivo insulin secretory dysfunction found in type-2 diabetes can
      lie solely at the level of defective insulin exocytosis.

PMID- 12510061
TI  - [Treatment of congenital clubfoot with the Ponseti method].
AB  - OBJECTIVES: This study aimed to present the author's early experience with the
      Ponseti technique in correcting clubfoot and to evaluate the need for aggressive
      surgery in the first year of life. METHODS: The study included 44 feet of 31
      patients (25 boys, 6 girls; mean age 3 months; range 4 days to 8 months) with
      idiopathic clubfoot deformities of grade II, III, or IV. Twenty-seven feet (19
      patients) had not received any treatment before. Twelve patients (17 feet) had
      had unsuccessful prior conservative treatment elsewhere. All patients had
      manipulation casting in accordance with the Ponseti technique, and percutaneous
      Achilles tenotomy was performed in the presence of persistent equinus.
      Maintenance of correction was obtained with the use of a foot abduction brace.
      The mean follow-up period was 18 months (range 6.5 to 40 months). RESULTS: Forty
      two feet (95%, 29 patients) were treated successfully using the Ponseti method.
      In terms of compliance with the foot abduction brace, a significant difference
      was noted between patients without previous treatment and those with deformities
      considered resistant to prior conservative treatment. The latter manifested more
      compliance with brace application. CONCLUSION: Ponseti method proved efficient in
      correcting idiopathic congenital clubfoot deformities irrespective of initial
      deformity grades, provided that the details of the technique are strictly adhered
      to. The results also suggest the role of brace application in order to avoid
      relapses along with the importance of increasing patients' compliance through
      family education and experienced orthotists.

PMID- 12510062
TI  - [Single-stage bilateral Pemberton's pericapsular osteotomy in bilateral
      developmental dysplasia of the hip].
AB  - OBJECTIVES: This study was designed to evaluate the results of single-stage
      bilateral Pemberton's pericapsular osteotomy with or without open reduction and
      to demonstrate its advantages over two separate consecutive interventions in
      bilateral developmental dysplasia of the hip (DDH). METHODS: This prospective
      study included 20 patients (14 girls, 6 boys; mean age 30 months; range 12 to 60
      months) with bilateral DDH, who underwent single-stage bilateral Pemberton's
      pericapsular osteotomy with (14 patients, group A1) or without (6 patients, group
      A2) open reduction. Twenty patients (16 girls, 4 boys; mean age 24 months; range
      13 to 47 months) with unilateral DDH, who underwent Pemberton's pericapsular
      osteotomy with (12 patients, group B1) or without (8 patients, group B2) open
      reduction were enrolled into the study as controls. Single- and two-stage
      procedures were compared with regard to improvement in the acetabular index,
      complications, mean duration of anesthesia, perioperative need for blood
      transfusion, length of hospital stay, initiation of walking, overall cost of
      antibiotic prophylaxis, and total hospital charge. RESULTS: There were no
      significant differences between A1 and B1, A2 and B2 groups with respect to mean
      age, gender, pre- and postoperative acetabular indices, and recovery times.
      However, duration of anesthesia, length of hospital stay, cost of antibiotic
      prophylaxis, and total hospital charges differed significantly. The amount of
      blood transfusion differed significantly only between groups A1 and B1. The
      length of hospital stay and cost of antibiotic prophylaxis in group A2 was twice
      as much as that of group B2. Increases in other parameters ranged between 22% to
      37%. No early or late complications were encountered. CONCLUSION: Single-stage
      bilateral Pemberton's pericapsular osteotomy in patients with bilateral DDH seems
      to have significant advantages over two separate consecutive interventions.
      However, increased risks of bilateral osteotomies require that sufficiently
      equipped and experienced anesthesiologic and surgical teams be available.

PMID- 12510063
TI  - [Treatment of residual obstetrical brachial plexus palsy with tendon transfer].
AB  - OBJECTIVES: We evaluated the results of the correction of adduction and internal
      rotation deformities of the shoulder associated with residual obstetrical
      brachial plexus palsy (OBPP) by the transfer of latissimus dorsi and teres major
      muscles to the rotator cuff. METHODS: In order to correct adduction and internal
      rotation deformities associated with residual OBPP, 10 patients (7 males, 3
      females; mean age 8.1 years; range 4 to 19 years) underwent transfer of the
      latissimus dorsi and teres major muscles to the rotator cuff and lengthening of
      the pectoralis major tendon with Z-plasty. The right and left extremities were
      affected in seven and three patients, respectively. Involvement of the C5-C6
      nerve roots was detected in four, and C5-C6-C7 nerve roots in six patients. In
      two patients with a positive Putti sign, axillary roentgenograms showed posterior
      subluxation of the humeral head, and magnetic resonance and computed tomography
      scans revealed type III glenohumeral deformity. Functional evaluations were made
      using a 5-point scoring system proposed by Mallet. The mean follow-up was 23.6
      months (range 5 to 42 months). RESULTS: Postoperatively, the mean abduction and
      external rotation were 134.5 degrees (range 95 degrees to 170 degrees ) and 70
      degrees (range 45 degrees to 90 degrees ), respectively. The mean global
      abduction score was 4, external rotation score was 4.2, and the scores assigned
      to the ability to move hand to the neck and mouth were 3.5. Of two patients with
      type III glenohumeral deformity, whose ages were four and 19 years, abduction and
      external rotation were 150 degrees and 45 degrees in the former, 135 degrees and
      70 degrees in the latter, respectively. CONCLUSION: The transfer of the
      latissimus dorsi and teres major tendons is a necessary procedure to restore
      external rotation and abduction functions of paralysed shoulders. Compared to
      other techniques employed, it offers obvious advantages in terms of ease and
      cost, as well.

PMID- 12510064
TI  - [Open reduction and intramedullary fixation through minimal incision with Ender
      nails in femoral fractures of children aged from 6 to 16 years].
AB  - OBJECTIVES: We evaluated functional and radiologic results of the treatment in
      patients aged 6 to 16 years, who underwent indirect reduction with Ender nails
      through minimal incisions for troublesome femoral fractures. METHODS: We treated
      femoral fractures of 20 children (3 girls, 17 boys; mean age 10 years; range 7 to
      15 years) by indirect reduction and relative stabilization with Ender nails
      through mini-incisions. Indications for intramedullary nailing were the presence
      of multiple fractures, accompanying head injuries, neurological or pathologic
      disorders. According to the Muller classification, there were two 32A1, three
      32A2, nine 32A3, three 32B1, and three 32B2 fractures. Secondary callus formation
      was monitored with follow-up serial x-ray examinations. Range of motion of the
      hips and knees, leg length discrepancy, and the femoral anteversion were examined
      clinically. The mean follow-up was 30.5 months (range 24 to 46 months). RESULTS:
      Surgery was performed after a mean of 4.5 days of admission. The mean hospital
      stay was 12 days. Full weight-bearing was achieved after a mean of 69 days (range
      45 to 98 days). Union was obtained in all patients without any complications.
      Ender nails were removed surgically after a mean of 10.3 months (range 6 to 16
      months). The femoral anteverison was more than 10 degrees in three patients. The
      mean leg length shortening was 0.35 cm (range 0 to 1 cm). CONCLUSION:
      Intramedullary nailing of femoral fractures with Ender nails through minimal
      incisions provides a safe and adequate stabilization in cases in which
      conservative treatment is likely to fail, and in multiple fractures, open
      fractures, coexistent head injuries, in mentally-retarded children, and in
      children aged from 6 to 16 years.

PMID- 12510065
TI  - [Evaluation of functional results following surgical treatment of supracondylar
      femoral fractures].
AB  - OBJECTIVES: We evaluated functional results of patients who underwent surgical
      treatment for supracondylar femoral fractures. METHODS: Functional results of
      surgical treatment for supracondylar femoral fractures were evaluated in 23
      patients (14 males, 9 females; mean age 34 years; range 14 to 64 years) with the
      use of the Neer and HSS (The Hospital for Special Surgery) scoring systems. The
      strength of the quadriceps muscle was measured using Cybex isokinetic testing.
      The mean follow-up was 52 months (range 13 to 160 months). RESULTS: The average
      HSS score was 93.8 (range 68 to 100) and the average Neer score was 90.1 (range
      55 to 100). The average losses of extension strength at 60 degrees /s and 180
      degrees /s were 27.30% and 22.13%, respectively. Statistically significant
      correlations were found between the losses of extension strength and the Neer and
      HSS scores (p<0.01). The results showed that the patient's age and sex, the
      length of time between trauma occurrence and surgery, immobilization period, and
      the presence of subjective pain complaints had no significant influence on the
      HSS and Neer scores and on Cybex isokinetic test results (p>0.05). CONCLUSION:
      Evaluation of the quadriceps muscle strength with the use of objective tests
      proved helpful in the determination of functional results of surgery following
      supracondylar femoral fractures.

PMID- 12510066
TI  - [Intramedullary nailing of adult femoral fractures].
AB  - OBJECTIVES: We evaluated the results of treatment of adult femoral fractures
      treated by intramedullary nails. METHODS: Sixty-two patients (15 females, 48
      males; mean age 29 years; range 16 to 62 years) with 64 femoral fractures were
      treated by intramedullary nailing. Eighty-three percent of the fractures was
      closed and 17% was open. According to the Winquist (W) classification, there were
      16 (25%) W0, 22 (34%) W1, nine (14%) W2, nine (14%) W3, and eight (13%) W4
      fractures. The mean duration between trauma and surgery was 18 days (range 4 to
      130 days), and the mean hospital stay was 25 days (range 11 to 142 days). Open
      and closed techniques were employed in 62 (97%) and two (3%) fractures,
      respectively. Nine fractures were unlocked; dynamic and static locking were
      performed in 39 and 16 fractures, respectively. In the open technique, secondary
      procedures involved grafting in 14 cases, cerclage in eight cases, grafting and
      cerclage in 10 cases, and grafting and screw fixation in one case. The results
      were assessed according to the criteria by Thoresen et al. The mean follow-up was
      28 months (range 7 to 62 months). RESULTS: Fifty-one patients (80%) had
      satisfactory, 13 patients (20%) had poor outcome. All proximal locking screws
      (n=20) were successfully inserted, whereas 23 (24%) of 95 distal screws missed
      the nail holes. Complications included superficial infection (n=3), osteomyelitis
      (n=4), trochanteric bursitis (n=1), irritation of the skin by the distal screws
      (n=4), heterotopic ossification (n=6), shortening more than 1 cm (n=8),
      rotational malalignment greater than 10 degrees (n=2), migration of the nail
      through the knee joint (n=2), drill breakage while preparing the distal holes
      (n=2), knee range of motion below 100 degrees (n=6), and delayed union (n=2).
      CONCLUSION: Intramedullary nailing should be the primary indication for stable
      and unstable femoral fractures.

PMID- 12510067
TI  - [Short-term results of treatment of humeral and tibial fractures with new
      inflatable intramedullary nails].
AB  - OBJECTIVES: We evaluated the effectiveness of a new inflatable intramedullary
      nail system in the treatment of tibial and humeral fractures. METHODS: The study
      included seven patients (4 men, 3 women; mean age 37.5 years; range 27 to 48
      years) whose humeral or tibial fractures were treated by new inflatable
      intramedullary nails. Five fractures were in the tibial diaphysis; three were
      humerus fractures. One patient had bilateral involvement. All tibial fractures
      and one humeral fracture were fresh, whereas two patients presented with delayed
      union. Treatment consisted of closed reduction and antegrade intramedullary
      nailing, with the addition of bone grafting in delayed unions. The patients were
      evaluated with regard to operation duration, healing periods, complications, and
      final clinical and radiologic findings. The mean follow-up period was 15.3 months
      (range 12 to 20 months). RESULTS: Operation time for both tibial and humeral
      fractures was less than that with other internal fixation techniques. The need
      for fluoroscopic monitoring decreased appreciably, as well. Healing times were
      similar to those of other intramedullary nailing systems. No complications
      occurred related to the use of the inflatable intramedullary nail system.
      CONCLUSION: The use of inflatable intramedullary nails may have significant
      implications in selected fractures, allowing easier stabilization of long bone
      fractures and saving valuable operation time.

PMID- 12510068
TI  - [Long-term functional results of adult intra-articular distal humeral fractures
      treated by open reduction and plate osteosynthesis].
AB  - OBJECTIVES: We assessed the long-term functional results of surgical treatment of
      distal intra-articular humeral fractures, together with the factors having
      influence on the outcome. METHODS: Thirty-four patients (25 males, 9 females;
      mean age 38 years; range 20 to 78 years) who were treated by open reduction and
      plate osteosynthesis were retrospectively evaluated. All fractures were type C
      according to the AO classification. Five patients had open fractures. Thirty
      three patients had surgery within the first two days after trauma. Posterior
      (n=19), lateral (n=13), and lateral and medial (n=2) incisions were used. Intra
      articular olecranon osteotomy was performed in 11 patients in whom a posterior
      incision was used. The mean follow-up period was 81.5 months (range 24 to 141
      months). Functional evaluation was made according to the criteria described by
      Jupiter et al. RESULTS: Postoperative complications included infection in four
      patients, nerve lesion in four patients, nonunion of the olecranon in one
      patient, and fixation failure in one patient. The mean elbow flexion was 115.1
      degrees, and the mean extension loss was 26.3 degrees. Four patients had severe
      pain and deformities. According to the criteria by Jupiter et al., the results
      were excellent in six (17.7%), good in 15 (44.1%), fair in nine (26.4%), and poor
      in four (11.8%) patients. The rate of excellent and good results were higher in
      closed fractures, in males, in patients at 20 to 40 years of age, in those
      undergoing posterior incisions and intra-articular olecranon osteotomy, and in
      patients in whom double-plate osteosynthesis was used. CONCLUSION: Our results
      suggest that age, gender, infection, preservation of neural function, successful
      rigid fixation, an anatomic restoration of the joint surface, and early
      rehabilitation are effective factors on the functional outcome.

PMID- 12510069
TI  - [Percutaneous extensor tenotomy in patients with lateral epicondylitis resistant
      to conservative treatment].
AB  - OBJECTIVES: We evaluated the results and advantages of percutaneous extensor
      tenotomy performed in patients with lateral epicondylitis resistant to
      conservative treatment. METHODS: Percutaneous extensor tenotomy was performed in
      nine patients (7 females, 2 males; mean age 44 years; range 32 to 54 years) with
      lateral epicondylitis unresponsive to conservative treatment. The mean duration
      of the complaints was 25 months (range 9 months to 4 years), during which a mean
      of 2.7 (range 2 to 4) local corticosteroid injections was administered. The
      patients were operated under local anesthesia in an outpatient setting. The
      procedure lasted approximately 4.5 minutes. The remaining portion of the tendon
      was removed by manipulation. The results were evaluated according to the criteria
      by Verhaar et al. The mean follow-up period was nine months (range 4 to 15
      months). RESULTS: The patients were able to use their affected arms after a mean
      of nine days (range 6 to 14 days). Hematoma that developed in the lateral
      epicondyle distally in two patients resolved spontaneously. All patients'
      complaints of pain decreased by more than 50% within six to eight weeks. The
      results were excellent or good in eight patients and fair in one patient. All
      patients but one were satisfied with the result of tenotomy. CONCLUSION:
      Percutaneous extensor tenotomy is a simple procedure; it can be performed under
      outpatient settings, and yields favorable results in patients with lateral
      epicondylitis resistant to conservative treatment.

PMID- 12510070
TI  - [Primary fixation of displaced carpal scaphoid fractures with the Herbert-Whipple
      screw].
AB  - OBJECTIVES: We evaluated the results of primary open reduction and internal
      fixation with the Herbert-Whipple screw in acute displaced carpal scaphoid
      fractures. METHODS: The study included 10 patients with acute displaced carpal
      scaphoid fractures and one patient with transscaphoid perilunate fracture
      dislocation. All the patients were males (mean age 34 years; range 23 to 44
      years) and underwent primary open reduction and internal fixation with the
      Herbert-Whipple screw. The fractures were in the right and left wrists in nine
      and two patients, respectively. The mean follow-up period was 30 months (range 13
      to 58 months). RESULTS: No early or late complications were encountered. All
      fractures healed in a mean of 11 weeks (range 9 to 15 weeks). All patients
      returned to their previous employment between four and 14 weeks postoperatively,
      being a mean of five weeks (range 4 to 7 weeks) for those employed in office-work
      and 10 weeks (range 9 to 14 weeks) for others. CONCLUSION: Primary open reduction
      and internal fixation with the Herbert-Whipple screw of acute displaced and
      unstable scaphoid fractures is an easy and reliable method leading to an
      uneventful union. Early operative intervention may avoid malunion, carpal
      instability, and radiocarpal osteoarthrosis that are often associated with closed
      treatment of these complex fractures.

PMID- 12510071
TI  - [Analysis of the causes of failure in carpal tunnel syndrome surgery and the
      results of reoperation].
AB  - OBJECTIVES: We investigated the causes of failure and ensuing problems and
      findings in patients with unrelieved or recurrent carpal tunnel syndrome (CTS)
      and evaluated the results of revision surgery. METHODS: The study included 26
      patients (21 women, 5 men; mean age 52 years; range 30 to 71 years) who underwent
      reoperation for unrelieved or recurrent symptoms following at least a year (range
      1 to 4 years) after the initial surgery. A total of 34 operations had been
      carried out in 31 hands. All patients were investigated clinically and
      electrophysiologically. The mean follow-up after reoperation was 19 months (range
      12 to 38 months). RESULTS: The diagnosis was confirmed in all patients by
      clinical and electrophysiologic studies. The primary operations had been
      performed using 11 transverse incisions, three incisions confined proximally to
      the wrist crease, 10 incisions without insufficient distal extension, and seven
      appropriate incisions. The transverse carpal ligament release was inadequate in
      23 hands; it had not been released in three hands at all. Excessive fibrous
      tissue developed in one patient, leading to complete bilateral median nerve
      compression. Bilateral and unilateral tenosynovitis resulting from rheumatoid
      arthritis and tuberculosis was detected in two patients, respectively. All
      patients underwent repeat open carpal tunnel release. Neurolysis and
      tenosynovectomy were performed in both hands of one patient and in one hand of
      two patients, respectively. Clinical results were excellent in 24 hands, good in
      six hands, and fair in one hand. CONCLUSION: Selection of appropriate incision
      and achievement of complete carpal tunnel release without any injury to the
      median nerve or its branches are of great importance with regard to postoperative
      results. Careful imaging studies of the carpal tunnel should be carried out
      especially in patients with unilateral involvement, presenting with an atypical
      age or occupation.

PMID- 12510072
TI  - [Neural axis abnormalities detected by preoperative magnetic resonance imaging in
      patients with type III idiopathic scoliosis].
AB  - OBJECTIVES: We investigated the presence of neural axis abnormalities by magnetic
      resonance imaging (MRI) in patients with clinically and radiologically confirmed
      absolute flexible thoracic curves (King-Moe type III). METHODS: Preoperative MRI
      scans of 84 patients (34 males, 50 females; mean age 14.1 years; range 11 to 17
      years) with adolescent idiopathic scoliosis and a flexible thoracic curve (King
      Moe type III) were prospectively evaluated to determine neural axis
      abnormalities. Clinical and radiologic indications for preoperative MRI
      examination were sought. All patients were treated with posterior fusion. All
      patients were intraoperatively monitored by means of motor evoked potentials by
      magnetic transcortical stimulation and somatosensory evoked potentials. The mean
      follow-up was 50.1 months (range 24 to 105 months). RESULTS: Neural axis
      abnormalities were detected in six patients (7.1%), including syringomyelia in
      five patients (5.9%) and diastometamyelia in one patient (1.2%). Of 84 patients,
      51 patients (60.7%) had a relatively decreased spinal cord diameter, and an
      increased epidural distance. No clinical or radiologic indicators were found for
      preoperative MRI examination. No neurologic deficits developed during operation
      and in the postoperative period. CONCLUSION: The detection of neural axis
      abnormalities implies the necessity of intraoperative neurologic monitoring to
      minimize the risks for neurologic deficits. Where this is not available,
      preoperative MRI seems to be an essential tool in the prevention of surgery
      associated neurologic risks.

PMID- 12510073
TI  - [Tibial plateau fracture following oblique osteotomy of the tibial tubercle: a
      case report].
AB  - Oblique osteotomy of the tibial tubercle is a preferred technique in
      patellofemoral disorders, resulting in a satisfactory clinical outcome. However,
      postoperative fractures of the proximal metaphysis of the tibia may often
      develop. An incomplete fracture of the lateral tibial plateau occurred in a 23
      year-old female patient following an oblique osteotomy of the tibial tubercle.
      There was no history of trauma. The patient had undergone two operations in the
      same knee due to patellar instability. She also had bilateral high congenital hip
      dislocation. The correct diagnosis could only be made by computed tomography.
      Complete union was obtained following six weeks of plaster cast fixation. Due to
      inherent biomechanical limitations, complications may arise following oblique
      osteotomy of the tibial tubercle even adequate care is given to the surgical
      technique.

PMID- 12510074
TI  - [Traumatic anterior dislocation of the hip associated with ipsilateral femoral
      neck fracture: a case report].
AB  - A thirty-nine-year-old female patient was brought to the emergency room following
      an automobile accident. Radiographic examination revealed a subcapital fracture
      of the left femur associated with anterior femoral head dislocation, and a
      contralateral comminuted femoral shaft fracture. Computed tomography showed that
      the acetabulum was empty, with the femoral head dislocated anteriorly close to
      the obturator foramen. Uncemented total hip arthroplasty and locked
      intramedullary nailing were performed on the left and right sides, respectively.
      Sixty-two months after surgery, she had no difficulty in performing daily
      activities.

PMID- 12510075
TI  - [Total hip arthroplasty and problems encountered in patients with high-riding
      developmental dysplasia of the hip].
AB  - OBJECTIVES: We evaluated total hip arthroplasty in patients with high-riding
      developmental dysplasia of the hip with regard to surgical method and
      modifications, problems encountered during surgery, and follow-up results.
      METHODS: A total of 42 hips (22 Crowe type III, 20 type IV) of 31 patients (29
      women, 2 men; mean age 45.7 years; range 26-70 years) who underwent total hip
      arthroplasty were clinically and radiologically evaluated. In all cases,
      cementless acetabular components were placed in the true acetabulum. Fifteen
      acetabula required structural autografts. Cementless stems were used on the
      femoral side. Proximal metaphyseal step-cut osteotomy was performed in patients
      with high-riding hips of more than 4 cm. The mean follow-up period was 54.7
      months (range 11 to 127 months). RESULTS: The mean Harris hip score increased
      from 37.6 preoperatively to 91.02 at the end of follow-up. No acetabular
      autograft resorption or non-union were observed. Non-union and delayed union in
      the femoral osteotomy site were encountered in two patients, respectively. Two
      components (1 acetabular, 1 femoral) were revised during the follow-up period.
      Two sciatic and two femoral temporary nerve palsies occurred. One patient
      developed superficial infection and was treated by debridement and antibiotics.
      Brooker type I heterotopic ossification was observed in seven patients.
      CONCLUSION: Total hip arthroplasty proved successful in high-riding developmental
      dysplasia of the hip.

PMID- 12510076
TI  - [Cemented total hip arthroplasty for severe dysplasia or congenital dislocation
      of the hip].
AB  - OBJECTIVES: We evaluated total hip arthroplasty and short-term results in the
      treatment of coxarthrosis due to neglected congenital dislocation or severe
      dysplasia of the hip. METHODS: Cemented total hip arthroplasty was performed in
      23 hips of 22 patients (2 men, 20 women; mean age 48.6 years; range 28 to 65
      years) with osteoarthrosis due to congenital dislocation or severe dysplasia of
      the hip. The acetabular component was placed at the level of the true acetabulum;
      four patients required augmentation with autogenous bone grafts due to severe
      acetabular deficiency. Femoral shortening osteotomy using a subtrochanteric step
      cut osteotomy was performed in seven patients with high-riding hips. Five
      patients underwent proximal femoral shortening after the trochanter major was
      osteotomized and distally advanced. All patients were evaluated with the use of
      the Merle d'Aubigne and Postel hip scores. Radiologic evaluations were made by
      preoperative and follow-up radiographs. The mean follow-up was 52.8 months (range
      30 to 108 months). RESULTS: According to the Merle d'Aubigne and Postel hip
      scores, the results were excellent in 17 hips (74%), good in four hips (18%),
      fair in one hip (4%), and poor in one hip (4%). One hip required revision because
      of nonunion of the acetabular graft. The femoral stem was fractured in one
      patient. Complications included temporary sciatic nerve palsy in one patient,
      deep venous thrombosis in one patient, early dislocation in one patient, and
      nonunion of the femur in one patient who underwent subtrochanteric step-cut
      osteotomy. CONCLUSION: Total hip arthroplasty for congenitally dislocated or
      severely dysplastic hips is more effective than other treatment methods. Long
      term results can be improved by the use of contemporary cementing techniques.

PMID- 12510077
TI  - [Is sufficient femoral head coverage obtained after Pemberton's pericapsular
      osteotomy? Evaluation by three-dimensional computed tomographic reconstruction].
AB  - OBJECTIVES: We evaluated femoral head coverage by three-dimensional computed
      tomographic reconstruction after Pemberton's pericapsular osteotomy with open
      reduction in cases with developmental dysplasia of the hip. METHODS: In a
      prospective design, routine radiographs of 15 consecutive patients were obtained
      and three-dimensional computed tomographic reconstruction was performed
      preoperatively and six months after surgery. The mean age at the time of surgery
      was 26 months (range 18 to 34 months). Twelve patients were girls and three were
      boys. RESULTS: The mean acetabular index was 38 degrees (range 33 degrees -52
      degrees ) preoperatively, and 19 degrees (range 16 degrees -23 degrees )
      postoperatively. Comparison between pre- and postoperative three-dimensional
      computed tomographic reconstruction images revealed increased acetabular
      adduction and extension, and decreased acetabular anteversion in all cases.
      Sufficient coverage of the femoral head was documented in all patients.
      CONCLUSION: Pemberton's pericapsular osteotomy provides successful results in
      appropriate cases, with sufficient coverage of the femoral head. However, if
      there is any doubt, utilization of three-dimensional computed tomographic
      reconstruction images may contribute to a more precise evaluation of the outcome.

PMID- 12510078
TI  - [Treatment of femoral shaft fractures with interlocking intramedullary nailing].
AB  - OBJECTIVES: Fractures of the femoral shaft are one of the most common fractures
      and may result in extensive disability, prolonged morbidity, or mortality unless
      appropriate treatment is applied. There are several treatment alternatives. In
      this study, we evaluated early results of interlocking intramedullary nailing in
      patients with femoral shaft fractures. METHODS: Femoral fractures of 42 patients
      (34 males, 8 females; mean age 32 years; range 16 to 67 years) were treated with
      interlocking intramedullary nailing. The mean follow-up was 14.4 months (range 8
      to 32 months). Radiologic and clinical results were evaluated. RESULTS: Union was
      obtained in all but one patient within a mean duration of 18.2 weeks. Discrepancy
      of leg length was measured as 10 mm in six patients, and 25 mm in one patient.
      One patient (2.38%) developed deep infection. Knee flexion was more than 120
      degrees in 95.23%. According to Thoresen's criteria, the results were excellent
      and good in 89% of patients. CONCLUSION: Interlocking intramedullary nailing
      proved an acceptable alternative in the treatment of femoral shaft fractures.

PMID- 12510079
TI  - [Intramedullary stabilization of pediatric diaphyseal femur fractures with
      elastic Ender nails].
AB  - OBJECTIVES: We evaluated the results of intramedullary stabilization of pediatric
      diaphyseal femur fractures with elastic Ender nails. METHODS: Twenty-six children
      (19 boys, 7 girls, mean age 8.9 years, range 5.9 to 12.3 years) were stabilized
      with flexible intramedullary Ender nails placed by the retrograde technique.
      Nineteen were isolated femoral fractures. The fractures occurred in the middle
      third (n=18), distal third (n=5), and proximal third (n=3) of the femur. The mean
      follow-up was 22.3 months (range 8 to 47 months). Radiologically, anteroposterior
      and lateral radiographs were evaluated. To determine leg length discrepancy, 25
      children had scanograms beyond 12 months. Clinically, the level of the hip and
      knee motion and walking patterns were evaluated. RESULTS: Union was achieved in
      all patients within a mean of 6.6 weeks (range 5 to 12 weeks). Twenty-four
      fractures healed with a normal anteroposterior alignment while two children had 5
      degrees varus and 7 degrees valgus, respectively. Lateral radiographs showed an
      anterior angulation of 7 degrees and a posterior angulation of 6 degrees in two
      patients, respectively. The femur length remained equal to that of the
      contralateral side in 19 patients (76%), whereas it exceeded by a mean of 7 mm in
      four, and shortened by a mean of 6 mm in two children. All patients but one had a
      symmetric walking pattern. All children but one had a normal range of hip and
      knee motion. No instances were observed concerning delayed union, infection,
      nonunion, rod fractures, growth arrest, injury to the femoral epiphysis, or
      refractures after rod removal. CONCLUSION: Intramedullary nailing with the use of
      elastic Ender nails provided effective fixation in the treatment of femoral shaft
      fractures in children 6 to 12 years of age.

PMID- 12510080
TI  - [Arthroscopic meniscal repair with the use of conventional suturing materials].
AB  - OBJECTIVES: We evaluated the mid-term clinical results of patients who underwent
      arthroscopic meniscal repair. METHODS: Sixty-one patients (43 males, 18 females;
      mean age 26.9 years; range 17 to 42 years) underwent meniscal repair using
      conventional suture techniques for unstable vertical longitudinal meniscal tears
      in the peripheral vascular zone, measuring more than 1 cm. All patients had an
      adequate follow-up. The involved side was right in 34 patients, and left in 27
      patients. The localization was medial in 36 tears, and lateral in 25 tears.
      Arthroscopic meniscal repair technique was inside-out in 47 cases, and outside-in
      in 14 cases. Associated lesions were anterior cruciate ligament tears in 24
      patients, and tibial plateau fractures in five patients, all of which were
      treated simultaneously. The patients were evaluated with the use of a modified
      Marshall knee scoring system. The mean follow-up was 44 months (range 12 to 72
      months). RESULTS: The results were excellent in 41 patients, good in 14 patients,
      fair in three patients, and poor in three patients. Limited range of motion seen
      in four knees postoperatively was successfully treated by arthroscopic release
      and an intense rehabilitation program. All patients returned to sports activities
      within a mean of six months. Second-look arthroscopy performed in 20 patients
      after a mean of six months postoperatively showed complete healing of the
      involved menisci in 17 patients. CONCLUSION: Meniscal tears occurring in the
      peripheral vascular zone without any injury to the meniscal body can be
      successfully repaired using conventional suture techniques.

PMID- 12510081
TI  - [Removal of the wadding from the wound in shotgun-pellet injuries].
AB  - OBJECTIVES: Most of the gunshot injuries are caused by low-velocity bullets and
      shotgun pellets, resulting in mild soft tissue damage. They are sometimes
      associated with vascular involvement and fractures depending on the angle of
      entry. Bullets and especially pellets usually lodge in soft tissues. For those
      that are not easily detected, surgical exploration is not recommended unless they
      are of vital localizations. However, the removal of wadding, which may incite a
      local inflammatory response and harbor bacterial contaminants, is strongly
      recommended. METHODS: Of forty-one patients with shotgun injuries, eight patients
      were found to bear waddings that required removal. RESULTS: Waddings made of cork
      and plastic were removed from one and seven patients, respectively. In addition
      to patients' histories and wound-related features, radiolucent plastic waddings
      were predicted by the presence of a cluster of pellets on radiographs. Fractures
      were encountered in the injured extremity in six patients. No infections
      developed related to the primary wound. CONCLUSION: Although it is often
      difficult to locate a lodged wadding in the body, its removal is necessary
      because it can incite a local inflammatory response and harbor bacterial
      contaminants.

PMID- 12510082
TI  - [The results of surgical treatment in ankle fractures].
AB  - OBJECTIVES: We evaluated the results of surgical treatment for ankle fractures
      and the factors that play a role in these results. METHODS: The study included 31
      patients (20 men, 11 women, mean age 38.2 years) who underwent surgical treatment
      for ankle fractures and had an adequate follow-up. According to the Lauge-Hansen
      classification, the mechanism of occurrence was supination-external rotation in
      13 (42%), pronation-external rotation in two (26%), pronation-abduction in four
      (13%), and supination-abduction in four patients (13%). In two patients (6%), the
      fractures could not be classified. Most of the fractures occurred with falling in
      winter months. The majority of fractures (55%) was of bimalleolar type. The mean
      follow-up was 26 months. RESULTS: Union was obtained in all fractures. According
      to the objective criteria, the results were good, moderate, and poor in 18 (58%),
      eight (26%), and five (16%) patients, respectively. Subjective evaluation yielded
      good, moderate, and poor results in 17 (55%), eight (26%), and six (19%)
      patients, respectively. The results were poor especially in pronation-external
      rotation and fracture-dislocation type fractures. Two patients (6%) developed
      degenerative arthritis. CONCLUSION: In our opinion, the best anatomical reduction
      may be achieved by surgical treatment of ankle fractures that present with a
      talar tilt, fibular shortening, and injury to the syndesmosis.

PMID- 12510083
TI  - [The effect of deep deltoid ligament release on dorsiflexion in congenital
      clubfoot treated with complete subtalar release].
AB  - OBJECTIVES: We evaluated the effect of releasing the posterior half of the deep
      branches of the deltoid ligament on dorsiflexion capacity of the ankle in
      congenital clubfoot treated with complete subtalar release (CSTR). METHODS: Fifty
      two feet of 35 patients with clubfeet were treated with CSTR. The patients were
      divided into two groups depending on the absence (group I) or presence (group II)
      of posterior deltoid ligament release. The groups consisted of 13 patients (21
      feet) and 22 patients (31 feet), respectively. The original Cincinnati incision
      was used in all cases. In addition to the classical CSTR, posterior half of the
      deep branches of the deltoid ligament was released in group II. Both groups
      received the same postoperative care. The mean postoperative follow-up period was
      55.5 months (range 36-77 months) in group I, and 24.7 months (range 10-37 months)
      in group II. The results were evaluated radiographically by measuring the talo
      tibial and calcaneal inclination angles. RESULTS: It was observed that the
      calcaneus remained in equinus in both groups. Although posterior deltoid ligament
      release appreciably increased the dorsiflexion perioperatively, this did not
      represent a statistically significant functional improvement in group II.
      CONCLUSION: Although the foot could be dorsiflexed and the talar dome observed
      posteriorly upon the release of the posterior half of the deep branches of the
      deltoid ligament, no beneficial clinical effect was observed because the tendo
      calcaneus could not be lengthened sufficiently.

PMID- 12510084
TI  - [The effect of percutaneous trigger finger release on normal anatomic structures
      and long-term results of the procedure].
AB  - OBJECTIVES: To evaluate the long-term results and possible complications of
      percutaneous release in the treatment of trigger finger. METHODS: We performed
      percutaneous pulley release with the use of a 16 gauge needle in 25 fingers of 22
      patients (16 females, 6 males; mean age 54 years; range 45 to 72 years). Open
      exploration was added to the procedure in 10 patients to determine the efficacy
      and safety of the technique. The mean follow-up was 24 months (range 18 to 35
      months). RESULTS: Triggering and pain were eliminated in all fingers
      postoperatively. Exploration showed that a complete anatomical release of the
      pulley was obtained in all fingers. Apart from some superficial abrasions, there
      were no tendinous injury or other complications. In one case, an unintentional
      skin incision occurred during manipulation of the needle. CONCLUSION: Due to low
      complication rates and ease of the procedure with a successful release,
      percutaneous technique proved an appropriate alternative in the treatment of
      trigger finger.

PMID- 12510085
TI  - [The results of open surgical release in carpal tunnel syndrome and evaluation of
      follow-up criteria].
AB  - OBJECTIVES: We evaluated the results of open surgical release in patients with
      carpal tunnel syndrome (CTS) and assessed the necessity of a clinical scoring
      system and electromyography (EMG) in the postoperative follow-up. METHODS: The
      study included 24 wrists of 15 patients (9 females, 6 males; mean age 49.2 years;
      range 23 to 70 years) in whom a diagnosis of CTS was made by clinical examination
      and EMG. The patients underwent open surgical release and were followed-up for a
      mean of 21.5 months (range 7 to 40 months), during which they were evaluated by
      the Boston scale (BS) for clinical scoring and EMG. Postoperative findings of BS
      and EMG were compared in terms of their utility during follow-up. RESULTS:
      Statistically significant differences were found between preoperative and follow
      up EMG values of motor distal latency, sensorial latency, combined motor muscle
      potential amplitudes, and sensorial latency amplitudes (p<0.05). Of twenty-four
      wrists, 16 (66.6%) showed improvement, and eight (33.3%) showed marked
      improvement. Similarly, preoperative and follow-up BS scores showed significant
      differences in favor of treatment results (p<0.05). The Boston scale scores and
      EMG results were found consistent in showing treatment outcome. CONCLUSION: Open
      surgical release of CTS provides favorable results that can be sufficiently
      evaluated by the clinical scoring system alone. Electromyographic studies do not
      seem to add extra benefits to the postoperative evaluation of patients with CTS.

PMID- 12510086
TI  - [A case of bilateral unicameral bone cyst of the calcaneus and surgical outcome].
AB  - Bilateral unicameral bone cysts of the calcaneus are extremely uncommon. A
      sixteen-year-old female presented with bilateral heel pain. Conventional
      radiographs and computed tomography showed cystic lesions and cameral cystic
      formation. Curettage and bone grafting were performed. The patient had no
      complaints in the postoperative 38th month. Radiologically, no recurrence was
      observed.

PMID- 12510087
TI  - [Injury to the spinal cord without any radiographic abnormality in a child].
AB  - Spinal cord injury without radiographic abnormalities (SCIWORA) is a diagnostic
      challenge most commonly encountered in pediatric patients. The unique
      hypermobility and ligamentous laxity of the pediatric bony cervical and thoracic
      spine may predispose to SCIWORA. A four-year-old girl was admitted for
      polytrauma. During monitorization deterioration in her neurological status was
      observed. Magnetic resonance imaging (MRI) showed an abnormal intensity in the
      spinal cord at the level of T11-L3, suggesting SCIWORA. We did not consider
      surgery and treated the patient with a conservative approach and rehabilitation
      program. The patient achieved a functional capacity sufficient to perform
      essential activities. A detailed neurologic examination should be undertaken
      particularly in polytrauma pediatric patients and MRI should be employed in
      suspected cases.

PMID- 12510088
TI  - [Total knee arthroplasty: a 4.5-year follow-up].
AB  - OBJECTIVES: To present the short- and mid-term follow-up results of primary total
      knee arthroplasty. METHODS: We performed a total of 97 cemented total knee
      replacements (47 right, 50 left) with posterior cruciate ligament retention in 66
      patients (60 women, 6 men). The mean age at the time of surgery was 65.2 years
      (range 29 to 82 years). Preoperative diagnoses were primary osteoarthrosis
      (n=60), rheumatoid arthritis (n=3), systemic lupus erythematosus (n=2), and post
      traumatic osteoarthritis (n=1). Thirty-one patients had bilateral knee
      replacements, of which 29 were performed at the same session. Pre- and
      postoperative clinical evaluations were made according to the clinical rating
      system of the Knee Society. Radiographic evaluations were made according to the
      Fairbank's criteria preoperatively, and to the total knee arthroplasty
      radiographic evaluation and scoring system of the Knee Society postoperatively.
      The mean follow-up was 4.5 years (range 24 to 98 months). RESULTS: Clinical
      results were good or excellent in 94.8 percent of patients. Complications
      encountered were deep infection in two patients, patellar dislocation in two
      patients, deep venous thrombosis in two patients, and patellar tendon rupture in
      one patient. The mean increases in knee and functional scores were 42.94 and
      39.87, respectively. Improvement in the mean postoperative knee flexion was 35.72
      degrees. The mean leg alignment was 6.3 degrees valgus. No components required
      revision because of aseptic loosening. CONCLUSION: Posterior cruciate ligament
      retaining implants were found to yield successful clinical and radiologic results
      during short- and mid-term follow-up period.

PMID- 12510089
TI  - [Normal values of several acetabular angles on hip radiographs obtained from
      individuals living in the Eskisehir region].
AB  - OBJECTIVES: To determine the normal values of several radiographic acetabular
      angles in individuals of Eskisehir region. METHODS: The acetabular index (AI)
      angle, acetabular angle (AA) of Sharp and the ACM angle were measured in 1162
      normal hips (n=581, 251 males, 330 females; mean age 33 years; range 5 to 75
      years). For AI angle, Hilgenreiner's line and the line connecting the lower end
      points of the sclerotic lines of the acetabular roofs were used for reference in
      subjects between five to 11 years with an open Y cartilage and in those with
      closed Y cartilage, respectively. AA and ACM angles were measured by the same
      method in all subjects. RESULTS: The mean AI angle between 5-11 years was 12.9+/
      4.5 degrees; the upper normal limit for the Hilgenreiner's AI angle was derived
      as 22 degrees. The mean AI angle above age 11 was 3.3+/-4.7 degrees and the upper
      normal limit for the AI angle defined by Tonnis after age 11 was found as 13
      degrees. Significant linear correlations were found between the AI angle and age
      for 5-11 years (p=0.002) and above 11 years (p=0.001), respectively. The mean AA
      angle was 39.2+/-4.6 degrees. There was a significant linear correlation between
      the AA angle and age (p=0.001). The upper limits for the AA angle in normal
      juvenile, adolescent, and adult hips were found as 52 degrees, 49 degrees, and 45
      degrees, respectively. The mean ACM angle was 41.9+/-3.3 degrees. A significant
      linear correlation was observed between the ACM angle and age (p=0.001). The
      upper limit for the ACM angle in normal hips was assessed as 49 degrees in all
      age groups. CONCLUSION: The authors of this study propose that the normal limits
      of acetabular angles obtained from our own population be used as reference values
      in interpreting standard radiographs of the hip.

PMID- 12510090
TI  - [The importance of predicted risk factors in developmental hip dysplasia: an
      ultrasonographic screening program].
AB  - OBJECTIVES: To evaluate the role of the risk factors in the diagnosis of
      developmental hip dysplasia (DDH) by ultrasonographic screening. METHODS: The
      hips of 327 newborns (151 females, 176 males) with identifiable risk factors
      including family history (n=20), congenital muscular torticollis (n=19),
      oligohydramniosis (n=2), breech presentation (n=51), multiple gestation (n=6),
      pes calcaneovalgus (n=74), clubfoot (n=152), and postural metatarsus adductus
      (n=3) were examined clinically on the first day of life and by ultrasonography
      within two weeks after birth. The hips were evaluated according to the Graf
      method. RESULTS: Clinical examination of 239 newborns were normal. Of these,
      sonographic abnormalities were found in 15 newborns (6.3%). On the other hand,
      out of 88 newborns who were found clinically abnormal, ultrasonography findings
      were normal in 24 cases (27%). According to the Graf method, of 654 hips, 550
      were type 1, 81 were type 2a, 15 were type 2c, five were type D, two were type
      3a, and one was type 4. Treatment was required for only 19 infants (5.8%), four
      of whom had been found normal on clinical examination. CONCLUSION: Our data
      suggest that risk factors are important for early diagnosis of DDH, and that, due
      to detection of abnormal ultrasonography findings among newborns who had been
      found normal on clinical examination, screening of all newborns with
      ultrasonography seems to be essential regardless of the presence of any risk
      factors.

PMID- 12510091
TI  - [Correction of deformities and length discrepancies of the forearm in children by
      distraction osteogenesis].
AB  - OBJECTIVES: To review the results of correction of deformities and length
      discrepancies of the forearm in children. METHODS: We evaluated the results of
      distraction osteogenesis in 10 forearms of nine patients with forearm shortening
      and/or deformity. The mean age at the time of surgery was 10.2 years (range 5 to
      16 years). Etiologies included congenital radioulnar synostosis and preaxial
      longitudinal deficiency of the forearm (n=1), congenital radioulnar synostosis
      and shortening of the forearm (n=1), multiple hereditary osteochondromas (n=1),
      distal radial physeal arrest (n=1), Madelung's deformity (n=2), bilateral
      congenital forearm shortening due to postaxial acrofacial dysostosis syndrome
      (n=1), and defect nonunion of the radius alone (n=1) and with the ulna (n=1) with
      shortening. Ilizarov type circular external fixators and monoplanar Orthofix
      fixators were used in seven and three patients, respectively. The mean follow-up
      was four years and four months (range 1 to 9 years). RESULTS: The mean length
      gain was 36.7 mm (range 25 to 60 mm), which meant a mean increase by 31.5% (range
      14% to 66%). A satisfactory functional and cosmetic improvement was achieved in
      all patients. Bone consolidation occurred in three to 13 months without a need
      for bone grafting. The most common complication was callus deformity seen after
      the removal of the fixator. CONCLUSION: Lengthening of the forearm results in
      improved upper extremity function, especially in activities requiring equal arm
      length as well as better cosmetic appearance if adequate soft tissue is
      preserved.

PMID- 12510092
TI  - [Simultaneous ipsilateral humerus and forearm fractures in children].
AB  - OBJECTIVES: To evaluate the results of treatment with early reduction and
      internal fixation for simultaneous ipsilateral distal humerus and forearm
      fractures in children. METHODS: The study included six patients (1 girl, 5 boys;
      mean age 11.5 years; range 9 to 13 years) who underwent treatment for ipsilateral
      humerus distal and forearm fractures. Reduction and fixation of fractures were
      performed percutaneously or by mini-open incisions. At the end of the follow-up
      period, patients were evaluated according to the Flynn's criteria. Radiologic and
      functional results on the involved side were compared with that of the normal.
      The mean follow-up period was 35 months (range 24 to 52 months). RESULTS:
      According to the Flynn's criteria, radiologic outcome was perfect in four
      patients (67%), and good in two (33%); functional results were perfect in three
      (50%), and good in three patients (50%). There were no significant differences
      between the two extremities with respect to elbow and wrist range of motion and
      radiologic parameters of the elbows. CONCLUSION: Early anatomic realignment of
      soft tissues and early active rehabilitation in simultaneous ipsilateral
      fractures of the distal humerus and forearm are significant factors for a
      satisfactory outcome. Treatment with early reduction and internal fixation with
      minimal soft tissue damage seems to be the method of choice in these fractures.

PMID- 12510093
TI  - [Plate fixation of closed femoral shaft fractures in adolescents].
AB  - OBJECTIVES: This study was designed to evaluate the results, advantages, and
      disadvantages of plate fixation of closed femoral shaft fractures in adolescents
      between the ages of 11 and 15 years. METHODS: The study included 35 adolescents
      (26 males, 9 females; mean age 13.4 years) who were treated by plate fixation for
      closed femoral shaft fractures and had an adequate follow-up. The fractures were
      bilateral in two patients, on the left in 17 patients (48%), and on the right in
      16 patients (45%). Traffic accidents were the most frequent etiology (57%).
      Nineteen patients presented with head injuries and/or multiple fractures. The
      mean follow-up was 34.9 months (range 22 to 156 months). RESULTS: All fractures
      healed in a mean of 10 weeks (range 6 to 16 weeks). No plate break or refractures
      occurred. Two patients had a loss of 20 degrees in knee flexion. Atrophy of the
      quadriceps muscle was observed in nine patients. Evaluations with the use of
      scanogram, orthorontgenogram, plain radiographs, and clinical examination showed
      an average overgrowth of 1.2 cm (range 0.4 to 1.6 cm). CONCLUSION: Despite some
      disadvantages, plate fixation seems to be an alternative method in the treatment
      of adolescent femoral fractures, enabling an anatomical reduction and stable
      internal fixation.

PMID- 12510094
TI  - [The results of plate fixation with the use of biological fixation principles and
      minimally invasive technique in femur fractures].
AB  - OBJECTIVES: We evaluated the clinical and radiologic results of patients treated
      by the minimally invasive technique and plate fixation in accordance with
      biological fixation principles for femoral fractures. METHODS: Biological
      fixation principles were used in the treatment of 24 patients (18 males, 6
      females; mean age 32 years; range 18 to 56 years) with femoral fractures.
      Fractures were reduced by indirect reduction and the plate was forwarded through
      distal and proximal incisions over the periosteum without the need for incisions
      on the fracture line. Fixation of the plates was performed with the use of screws
      from distal and proximal incisions. The patients were allowed partial and full
      weight-bearing in a mean of 3.6 and 5 months, respectively. By means of monthly
      clinical and radiologic examinations, union was assessed by callus formation in
      the fracture line and painless weight-bearing. In addition, leg length
      discrepancy, rotation, angulation deformities, and knee and hip range of motions
      were determined. The mean follow-up was 2 years and 7 months (range 16 months to
      4 years and 5 months). RESULTS: The mean union time was 4.6 months (range 4 to 11
      months). Except for one patient (4%) with delayed union, all patients achieved
      union. No infections occurred related to the fracture site. CONCLUSION:
      Successful clinical and radiologic results can be obtained by biological methods
      of fixation in diaphyseal femur fractures with multiple fragments, segment
      formation, in multi-trauma patients with high Injury Severity Score and
      compromised pulmonary function, and in those having subtrochanteric or
      supracondylar fractures associated with high complication rates.

PMID- 12510095
TI  - [The reliability of percutaneous osteotomy with the Gigli saw technique in the
      proximal tibia. A cadaveric study].
AB  - OBJECTIVES: To evaluate the reliability of percutaneous osteotomy with the use of
      a Gigli saw in the proximal tibia. METHODS: Forty-two attendants comprising of
      residents or consultants without any prior experience were assigned to 14
      cadaveric models to perform percutaneous osteotomy. The technique was first
      described by an experienced specialist and then illustrated on a cadaver
      specimen. Thereafter, the attendants performed osteotomy using a Gigli saw
      without any help by the instructors. Finally, exploration of the deep and
      superficial branches of the fibular nerve, posterior tibial nerve, posterior and
      anterior artery and vein was made with regard to any injury caused during
      osteotomy. RESULTS: There were ten incisional injuries in three specimens due to
      erroneous determination of the osteotomy level or incision. A mean of 3.5 cm
      (range 2.5 to 4.0 cm) incision length was observed in four specimens. No
      procedure-associated injuries to major nerves and vessels were documented except
      for those to the cutaneous branch of the superficial peroneal nerve in two
      specimens, and to the extensor hallucis longus muscle in one specimen. There was
      no incidence of incomplete osteotomy. CONCLUSION: Despite the lack of any prior
      experience with the osteotomy method with the Gigli saw on the part of the
      attendants, the full success in performing osteotomy confirms the reliability of
      the technique. Moreover, if this method is to be used by experienced surgeons,
      excellent results can be achieved without any injuries to cutaneous nerves and
      surrounding muscles.

PMID- 12510096
TI  - [The effect of continuous passive motion after repair of Achilles tendon
      ruptures: an experimental study in rabbits].
AB  - OBJECTIVES: The effect of continuous early passive motion on morphologic and
      histologic healing following repair of Achilles tendon rupture was evaluated in
      comparison with cast immobilization. METHODS: Achilles tendons of 20 adult
      rabbits were repaired with the use of modified Kessler technique after surgical
      transection. Throughout the postoperative six weeks, the rabbits were randomly
      assigned to cast immobilization (n=10) and to continuous early passive motion
      four hours a day (n=10). All the rabbits were sacrificed at the end of six weeks
      and their tendon tissues were removed for macroscopic and histologic
      examinations. RESULTS: On macroscopic evaluation, findings on adhesions at the
      operation site, periarticular atrophy, and the ROM of the ankle joint were found
      significantly more favorable with continuous early passive motion than those of
      the control group (p<0.001, p<0.05, and p<0.001, respectively). On histologic
      evaluation, regular collagen bundle alignment was 70% and 20% in the study and
      control groups, respectively (p<0.05), whereas findings on hyalinization and
      inflammatory infiltration were not significantly different. CONCLUSION: The
      utilization of continuous controlled passive motion following repair of Achilles
      tendon rupture was shown to have beneficial effects on tendon healing and ankle
      range of movement, without leading to eventual ruptures.

PMID- 12510097
TI  - [Comparison of autograft, coralline graft, and xenograft in promoting posterior
      spinal fusion].
AB  - OBJECTIVES: Bone grafting constitutes a vital component in many reconstructive
      orthopaedic surgical procedures. They are widely used in patients undergoing
      thoracolumbar spinal surgery. The three choices of bone are autograft, coralline
      graft, and xenograft. The purpose of this study was to evaluate the contribution
      of autograft, coralline graft, and xenograft to spinal fusion. METHODS: Thirty
      six New Zealand albino rabbits were divided into four groups of equal size.
      Decortication of posterior structures of the thoracal 10-12th vertebrae was
      performed in all rabbits. No graft material was used in group I (controls). The
      remaining three groups received autologous iliac crest bone graft, coralline
      graft, and xenograft dehydrated by solvents, respectively. The rabbits were
      sacrificed eight weeks postoperatively for manual, radiologic, histologic, and
      biomechanical evaluations. RESULTS: Manual and radiologic evaluations showed no
      fusion in the control group in which the lowest histologic and biomechanical
      scores were obtained. Manually and radiologically, fusion was found in 85.7% and
      in 78.5% with autologous iliac crest bone graft; in 61.1% and 61.1% with
      coralline graft, and in 55.5% and 50.0% with xenograft, respectively. CONCLUSION:
      Our data substantiates the use of coralline graft and xenograft as appropriate
      and efficient materials alternative to autografts in obtaining posterior spinal
      fusion.

PMID- 12510098
TI  - [Comparison of the effects of NG-monomethyl-L-arginine and indomethacin on
      tuberculous arthritis: an experimental study in rats].
AB  - OBJECTIVES: We evaluated therapeutic effects of NG-monomethyl-L-arginine (NMMA),
      a nitric-oxide synthase inhibitor, and indomethacin in a rat model of tuberculous
      arthritis. METHODS: Eighty male Wistar albino rats were randomly divided into
      five equal groups. In the first group (controls) normal saline solution was
      injected into the right knee joints of the rats. In the remaining groups,
      tuberculous arthritis was induced in the right knee joints of the rats via
      injection of 0.1 ml of a solution prepared from Mycobacterium tuberculosis
      strains. No treatment was given to the second group. The third and forth groups
      were assigned to receive oral indomethacin and intraperitoneal NMMA,
      respectively, while the fifth group received a combination thereof. The
      occurrence of arthritis was evaluated in four rats in each group on the 3rd, 7th,
      14th, and 21st days after induction of arthritis. The rats were then subjected to
      scintigraphic imaging with Tc99 and focal activity involvement was analysed. The
      ratio of joint to soft tissue was calculated quantitatively. Following sacrifice
      with ether anesthesia, nitrate/nitrite levels were measured via Griess reaction
      in the bone tissue adjoining the knee. The knee joints were histopathologically
      examined. RESULTS: The severity of arthritis in the NMMA group decreased by one
      point on the 14th day. On Day 21, arthritis score was zero in rats receiving a
      combination of indomethacin and NMMA. Scintigraphic examination revealed
      increased uptake activity on the 3rd and 7th days, whereas no uptake activity was
      seen on the 21st day in the group receiving both indomethacin and NMMA.
      Histopathologically, chronic inflammatory infiltration disappeared on Day 21 in
      rats receiving either NMMA alone or in combination with indomethacin. During the
      experiment, four rats in the second group and two rats in the third group died
      from sepsis. Nitrate measurements of the fifth group on Day 21 showed approximate
      values to those of the control group (p>0.05). CONCLUSION: The combined use of
      indomethacin and NMMA seems to be more efficacious in reducing negative effects
      of tuberculous arthritis on the joint.

PMID- 12510099
TI  - [The use of the cable-grip system in the treatment of winged scapula caused by
      post-traumatic combined nerve injury: a case report].
AB  - A twenty-three-year-old male patient developed winging of the scapula after a
      combined nerve injury following a gun-shot. Scapulothoracic arthrodesis was
      considered in order to relieve the patient's complaints. Stabilization of the
      scapulothoracic joint was performed using a hitherto undescribed method with the
      use of a cable-grip system (Doll-Miles Trochanter&Cable Grip System-Howmedica).
      After a seven-month follow-up, union was accomplished without any malposition;
      the patient's complaint of pain disappeared, shoulder imbalance was restored with
      an improvement in shoulder abduction from 70 degrees to 100 degrees and in
      flexion from 110 degrees to 160 degrees.

PMID- 12510100
TI  - [Repair of distal biceps brachii tendon rupture: a case report].
AB  - The rupture of the distal tendon of the biceps brachii muscle is a rarely
      encountered injury, causing flexion and supination losses. There are literature
      reports giving good results with the use of two-incision technique that fixes the
      distal biceps brachii tendon to the radial tuberosity. We used this technique in
      a 49-year-old male patient who had had left distal tendinous rupture of the
      biceps brachii muscle caused by lifting heavy weight. Functional evaluation at
      the end of 16 months with the use of the Cybex 350 test machine showed normal
      range of motions for flexion and extension in the left elbow. There was a 25
      percent loss of strength and 5 percent loss of endurance in flexion, and 11
      percent loss of endurance in pronation. No complications were observed and a very
      good functional result was achieved.

PMID- 12510101
TI  - [Lipofibromatous hamartoma of the median nerve].
AB  - Lipofibromatous hamartoma of the nerve is a very uncommon, congenital, benign,
      peripheral nerve tumor. It is mostly encountered in the extremities of young
      adults, involving the median nerve in the majority of cases. The nerve tissue is
      infiltrated by diffuse fibroadipose tissue which dissociates the fasciculi
      without invasion. Patients with lipofibromatous hamartoma of the median nerve
      usually present with symptoms of carpal tunnel syndrome, usually accompanied by
      marked macrodactyly. Lipofibromatous hamartoma of the median nerve was
      encountered in an 18-year-old female patient, involving the wrist, causing
      macrodactyly of the index finger, and resulting in symptoms of carpal tunnel
      syndrome. Median nerve release and partial excision of the adipose tissue along
      the mass were performed. Fourteen months postoperatively, the patient had no
      complaints and the mass decreased in size without any motor or sensory functional
      losses.

PMID- 12510102
TI  - [Traumatic femoral diaphyseal fracture and a bent intramedullary nail in a case
      with a completely healed femoral diaphyseal fracture].
AB  - Bending of a Kuntscher nail which had been used in the treatment of a prior
      femoral diaphyseal fracture was encountered in a 37-year-old male patient who was
      admitted to hospital for a deformity in his left thigh caused in a car accident.
      The nail was extracted and osteosynthesis was performed via an intramedullary
      locked nail. Union was obtained in the fourth postoperative month without any
      complications.

PMID- 12510103
TI  - [Arthroscopic-assisted mini-open rotator cuff repair].
AB  - OBJECTIVES: New alternatives have been developed in rotator cuff repair with
      advances in arthroscopic techniques. We evaluated retrospectively the results of
      our patients who underwent arthroscopic-assisted mini-open rotator cuff repair.
      METHODS: Arthroscopic subacromial decompression and mini-open repair were
      performed in 31 patients (8 males, 23 females; mean age 54.3 years; range 38 to
      71 years) with rotator cuff tear in which the tendon tear had not been
      excessively retracted (till glenoid) and the muscle had not undergone fatty
      degeneration. Patients below 40 years of age were considered for surgery, while
      those between 40 to 60 years were initially treated with a rehabilitation program
      to relieve pain and gain motion before surgery. Surgery was reserved until after
      failure with a three-month rehabilitation program in patients above 60 years.
      Evaluations were based on physical and radiographic examinations and Constant
      scores. The mean follow-up period was 24.4 months (range 12 to 37 months).
      RESULTS: Twenty-five patients (81%) achieved excellent or good results and six
      patients (19%) had satisfactory results. The mean Constant score was 84.6. One
      patient developed joint stiffness unresponsive to conservative treatment.
      Arthroscopic capsular release followed by a heavy exercise program enabled him to
      return to his former sports activity level within three months. CONCLUSION:
      Arthroscopic-assisted repair is a superior alternative in rotator cuff surgery in
      selected cases because it enables the shoulder surgeon to preserve deltoid
      attachment and to prepare the torn tendon for an easy repair. It may result in
      shortened hospital stay, decreased postoperative pain, and an accelerated
      rehabilitation.

PMID- 12510104
TI  - [Results of conservative treatment of displaced mid-clavicular fractures in
      adults].
AB  - OBJECTIVES: We evaluated the mid-term results of conservative treatment of mid
      clavicular fractures in adults. METHODS: Eighty-five patients (60 males, 25
      females; mean age 36 years; range 19-61 years) with mid-clavicular fractures were
      treated conservatively with a figure-of-eight bandage method. Radiographically,
      72 fractures were displaced and of two fragments, 13 were displaced and
      comminuted. Clinical and radiologic results were evaluated after a mean follow-up
      of 35 months (range 12 to 72 months). RESULTS: In 84 patients, union was achieved
      by conservative treatment. Only one patient required surgical treatment. Malunion
      occurred in seven patients. Clinically, the results were good in 68 (94.4%),
      moderate in three patients (4.1%), and poor in one patient (1.3%) in two-fragment
      fractures. Of comminuted fractures, the results were good in 10 (76.9%), and
      moderate in three patients (23.1%). No significant differences were found between
      the clinical results. CONCLUSION: Conservative treatment of displaced mid
      clavicular fractures provide union, making surgical treatment indicated only in a
      small number of patients with unsatisfactory results.

PMID- 12510105
TI  - [Results of excision of the radial head in comminuted fractures].
AB  - OBJECTIVES: To evaluate the results of radial head excision in the treatment of
      comminuted radial head fractures. METHODS: The study included 20 patients (14
      men, 6 women; mean age 34 years; range 21 to 55 years) who underwent radial head
      excision for comminuted, closed fractures. Sixteen patients had Mason type 3 and
      four patients had type 4 fractures. Surgery was performed at a mean of eight days
      after trauma (range 1 to 30 days). Patients were assessed with regard to whether
      they were able to return their former activities and work, and whether they had
      pain, limitation, loss of strength, and instability. The results were evaluated
      by the Radin and Riseborough's classification. The mean follow-up period was
      seven years (range 2 to 12 years). RESULTS: Sixteen patients (80%) re-gained
      their previous activities or work. Nine patients became asymptomatic. Five
      patients complained of loss of strength in the arm. Pain associated with weight
      bearing was observed in two patients in the wrist and elbow, respectively, and in
      both in two patients. Two patients had limitation of more than 30 degrees in at
      least one of extension, flexion, supination, or pronation. Five patients had
      mediolateral instability. The mean elbow flexion was 125 degrees (range 100 to
      140 degrees). Proximal migration of the radius was detected in five patients (1
      mm), two patients (3 mm), and in three patients (5 mm). According to the Radin
      and Riseboroughs classification, nine (45%), seven (35%), and four (20%) patients
      had good, fair, and poor results, respectively. CONCLUSION: Despite its relevance
      in elbow kinematics, our results seem to justify excision of the radial head in
      Mason type 3 comminuted radial head fractures where internal fixation presents
      severe difficulties.

PMID- 12510106
TI  - [Comparison between fixation with Herbert screws and Kirschner wires in the
      treatment of scaphoid pseudoarthrosis].
AB  - OBJECTIVES: To compare the treatment results of patients with scaphoid
      pseudoarthrosis, who were treated by autogenous cancellous bone grafting followed
      by fixation with Herbert screws or Kirschner wires. METHODS: The study included
      19 men (mean age 28 years, range 20 to 41 years) who were treated for scaphoid
      pseudoarthrosis and had a minimum follow-up of 12 months. Treatment was comprised
      of autogenous cancellous bone grafting and fixation with Herbert screws (n=10) or
      Kirschner wires (n=9). Fifteen right and four left hands were affected. The mean
      duration between the traumatic event and surgery was 20 months (range 3 to 72
      months). Fractures were localized in the proximal pole (n=4, 21%), waist (n=13,
      68%), and in the distal pole (n=2, 11%). The mean follow-up was 16 months for
      Herbert screws, and 21 months for Kirschner wires. RESULTS: None of the patients
      exhibited a loss in range of motion of 10 degrees or more. The mean time to union
      was six months (range 3 to 20 months) with Herbert screws and eight months (range
      4 to 22 months) with Kirschner wires. All patients had union with Kirschner
      wires, whereas non-union occurred in three patients with Herbert screws, two of
      whom had had proximal pole fractures. Radiologic outcome was significantly
      different between the two groups (p<0.01). CONCLUSION: Because of good
      vascularity and union potential, scaphoid pseudoarthrosis can be successfully
      treated by an appropriate surgical technique using autogenous cancellous grafting
      independent of fixation materials.

PMID- 12510107
TI  - [The role of magnetic resonance imaging in carpal tunnel syndrome. Correlation of
      clinical, electrodiagnostic, and intraoperative findings and staging].
AB  - OBJECTIVES: A prospective, single-blind study was planned to investigate the role
      of magnetic resonance imaging (MRI) in the diagnosis, treatment, and staging of
      carpal tunnel syndrome (CTS). METHODS: The study group was comprised of 43 hands
      of 25 patients (21 women, 4 men; mean age 56 years) with a clinical diagnosis of
      CTS. Fifteen patients (12 women, 3 men; mean age 51 years) with ganglions on the
      dorsal side of the wrist constituted the control group. Comparisons were made
      between MRI findings, clinical findings, electrodiagnostic test results, and
      intraoperative findings. RESULTS: Electrodiagnostic test results were positive in
      36 (84%) and negative in seven hands (16%). Magnetic resonance imaging revealed
      positive findings for CTS in all patients. A significant difference was found
      between the study and control groups in the carpal tunnel measurements at the
      level of the hook of the hamate (p<0.005). In addition, MRI showed space
      occupying lesions within the carpal tunnel in three patients, and a bilateral
      anomaly of the median nerve in one patient. CONCLUSION: It was found that MRI
      offered objective findings for the diagnosis, treatment, and staging of CTS,
      which were in good correlation with clinical findings, electrodiagnostic test
      results, and intraoperative observations. Moreover, it was helpful in the
      diagnosis when there had been discrepancy between clinical findings and
      electrodiagnostic test results.

PMID- 12510108
TI  - [Diagnostic arthroscopy and mini-open lateral retinacular release in the
      treatment of excessive lateral compression syndrome].
AB  - OBJECTIVES: We investigated the efficacy of diagnostic arthroscopy and mini-open
      lateral retinacular release in the treatment of excessive lateral compression
      syndrome. METHODS: Twenty patients (21 knees) with excessive lateral compression
      syndrome underwent diagnostic arthroscopy and longitudinal mini-open lateral
      retinacular release. The patients were comprised of four men and 16 women (mean
      age 48.6 years; range 21 to 60 years). The results were evaluated according to
      the Lysholm scoring system. Preoperative and postoperative congruence angles were
      compared on the tangential patella roentgenograms. Statistical analysis was made
      using the Wilcoxon signed rank test. The mean follow-up was 10.5 months (range 3
      to 18 months). RESULTS: The mean preoperative Lysholm score increased from 61.28
      (range 29 to 76) to 85.57 (range 59 to 99) postoperatively. Only two patients
      (9%) exhibited decreases in the postoperative Lysholm scores. The mean
      preoperative congruence angle was +14.94 degrees. In all but two patients, the
      congruence angle was within normal ranges, with a mean correction of 12.42
      degrees. None of the patients developed hemarthrosis postoperatively. Pain relief
      and functional recovery were achieved in 91% of patients. CONCLUSION: Lateral
      retinacular release and proper patellofemoral realignment may provide a
      successful outcome in patients presenting with anterior knee pain due to
      excessive lateral compression syndrome.

PMID- 12510109
TI  - [Surgical management of intraarticular calcaneus fractures].
AB  - OBJECTIVES: We evaluated the midterm results of surgical treatment for
      intraarticular calcaneal fractures. METHODS: This study included 19 feet of 14
      patients with intraarticular fractures of the calcaneus. Twelve patients were
      males and two were females (mean age 28.3 years; range 17 to 54 years). The
      fractures were bilateral in five patients. In one patient the contralateral foot
      was treated conservatively. Anteroposterior, lateral, and tangential radiographs
      and computed tomography (CT) scans were obtained in all patients preoperatively.
      According to the Sanders CT classification, there were 10 type II, five type III,
      and four type IV fractures. An extensile lateral incision was performed in all
      patients but one to provide an anatomic reduction with the use of Sherman plates,
      screws, and staples. The patients were followed-up by radiographs and CT. The
      results were evaluated using the Maryland Foot Score. The mean follow-up was 32.7
      months (range 24 to 43 months). RESULTS: Radiographs and CT scans obtained in the
      early postoperative period showed that a complete anatomic reduction was achieved
      in 13 feet. According to the Maryland Foot Score, the results were excellent in
      five, good in eight, fair in four, and poor in two feet. None of the patients
      required a subsequent operation due to surgery-associated causes. CONCLUSION: The
      success of surgical treatment of intraarticular calcaneal fractures depends only
      on the achievement of an anatomic reduction and on maintaining it with a stable
      osteosynthesis using appropriate strength hardware.

PMID- 12510110
TI  - [A treatment algorithm for developmental dysplasia of the hip for infants 0 to 18
      months of age and its prospective results].
AB  - OBJECTIVES: We evaluated the results of treatment in patients who were treated
      according to an algorithm established for developmental dysplasia of the hip
      (DDH) during the first 18 months of life. METHODS: We developed an algorithm for
      DDH to be used in infants at 0 to 18 months of age. Patients who did not respond
      to, or who did not have the indication for, the use of Pavlik harness were
      treated according to our algorithm and evaluated prospectively. Thirty-three hips
      (24 patients; 21 girls, 3 boys; mean age 7.4 months; range 2.5 to 18 months) were
      followed-up for a mean of 42 months (range 15 to 90 months). Ultrasonographic
      evaluation was performed using the Graf method. Avascular necrosis was evaluated
      according to the Kalamchi and MacEwen classification, and radiological results
      according to the Severin classification. RESULTS: The mean acetabular index
      angles before and after treatment were 37.3 degrees (range 20 degrees to 58
      degrees ) and 21.8 degrees (range 15 degrees to 30 degrees ), respectively.
      According to the Kalamchi and MacEwen classification, six hips (18.2%) had type
      I, three hips (9.1%) had type II, and one hip (3%) had type III avascular
      necrosis. According to the Severin criteria, 21 hips were considered in group I,
      10 in group II, and two hips in group III. Acetabular osteotomies were performed
      in four hips. All patients had full range of motion without any pain and limp.
      CONCLUSION: Successful clinical results obtained in the hips treated according to
      this algorithm for DDH may serve to justify its use as a standard algorithm in
      the treatment of infants at ages 0 to 18 months.

PMID- 12510111
TI  - [Treatment of childhood unstable radius distal methaphysis fractures with closed
      reduction and percutaneous Kirschner wires].
AB  - OBJECTIVES: We evaluated the results of treatment with closed reduction and
      percutaneous Kirschner wires in childhood unstable radius distal methaphysis
      fractures. METHODS: Forty-four fractures of radius distal methaphysis of 43
      children (33 boys, 10 girls; mean age 11.7 years; range 8.6 to 16 years) were
      treated with immediate closed reduction and percutaneous Kirschner wires.
      Fractures with more than 50% displacement were considered unstable. A
      satisfactory reduction was defined as the presence of 80% cortical contact on
      anteroposterior and lateral x-rays, an angulation of less than 20 degrees and 15
      degrees at ages below and over 10 years, respectively, and the absence of
      malrotation. Clinically, the range of motion of the elbow and wrist, forearm
      rotation, and grip strength were measured and compared with those of the other
      side in the 12th postoperative week. A restriction of 10 degrees or more in
      relation to the other side was regarded as failure. Radiologic indications of
      failure in the postoperative sixth week were residual angulations of more than 15
      degrees and 10 degrees at ages below and above 10 years, respectively, and
      malrotation. RESULTS: Forty-one patients (93.2%) achieved a successful outcome.
      Failure was encountered in three patients (6.8%). Two patients developed type 1
      pin tract infection, which resolved with antibiotic therapy and wound care.
      Patients returned to their normal activities in a mean of 10 weeks. CONCLUSION:
      Closed reduction and the use of percutaneous Kirschner wires proved to be the
      choice of treatment in unstable radius distal methaphysis fractures in children.

PMID- 12510112
TI  - [Evaluation of unilateral total hip arthroplasty by a quantitative analysis of
      gait].
AB  - OBJECTIVES: The purpose of this prospective study was to assess changes in gait
      parameters after unilateral total hip arthroplasty and to correlate these
      objective changes with the results of subjective analyses. METHODS: Thirty-eight
      patients (21 women, 17 men; mean age 61 years) with unilateral degenerative hip
      disease were evaluated in order to investigate preoperative and postoperative
      gait characteristics with the use of a gait evaluation mat (Gait Rite, USA). Each
      patient underwent at least two postoperative gait evaluations in the sixth and
      twelfth months, respectively. Gait evaluations were also made in a control group
      of 50 individuals without any neuromuscular and skeletal disease. Clinical
      evaluations were made using the Harris hip scoring system. RESULTS: All patients
      exhibited poor subjective evaluations preoperatively (Harris hip score <70).
      Compared to controls, patients had decreased step length and velocity, but
      increased stance, step, double support and swing times. Postoperatively, gait
      characteristics did not differ from those elicited prior to surgery in the first
      six months; however, patients attained near-normal velocity in the twelfth month.
      The recorded values for step length, step time, and double support time were
      similar to those of controls in both extremities. CONCLUSION: This study showed
      that total hip arthroplasty considerably improved the gait characteristics of
      patients with degenerative arthritis, and that this improvement could be measured
      and recorded quantitatively with the use of a walking band.

PMID- 12510113
TI  - [Mechanical strength of antibiotic-impregnated bone cement on Day 0 and Day 15: a
      biomechanical study with Surgical Simplex P and teicoplanin].
AB  - OBJECTIVES: To determine the maximum amount of a specific antibiotic added to 40
      g acrylic bone cement in terms of the effect on mechanical properties of the bone
      cement on Day 0 and after antibiotic release on Day 15. METHODS: In an
      experimental design, eight teicoplanin doses (0, 400 mg, 800 mg, 1200 mg, 1600
      mg, 2000 mg, 3200 mg and 4000 mg) were added to bone cement (Surgical Simplex P).
      Specimens were prepared using the third generation cementing technique to
      determine the compressive strength and four-point bending strength according to
      ASTM and ISO standards, respectively. For each concentration, 10 samples were
      prepared for Day 0 and Day 15. Mechanical tests were performed on Day 0 and after
      antibiotic leaching in water at 37 degrees C on Day 15. 0 mg specimens served as
      controls and mechanical strengths for each antibiotic concentration on Day 0 and
      Day 15 were compared. RESULTS: In compression tests, Day 0 samples showed no
      significant differences, whereas Day 15 samples starting with 800 mg exhibited
      significant decreases in compressive strength. However, the compressive strengths
      were above the minimum standard of 70 MPa set by ASTM at all concentrations and
      in all groups. Four-point bending tests demonstrated significant decreases in
      strength starting with 1200 mg in Day 0 samples, and with 400 mg in Day 15
      samples. Four-point bending strengths of 2000 mg, 3200 mg, and 4000 mg samples
      decreased below, or approximated closely the minimum standard of 50 MPa set by
      ISO on Day 15. CONCLUSION: Our results suggest that the maximum amount of
      teicoplanin dose to be safely added to 40 g of Surgical Simplex P is 1600 mg when
      third generation cement mixing and application techniques are employed.

PMID- 12510114
TI  - [Primary giant hydatid cyst in the thigh].
AB  - Human hydatid cyst is a zoonotic infection that usually attacks visceral organs.
      Primary soft tissue involvement is very rare, causing a diagnostic challenge.
      Primary soft tissue hydatid cyst was encountered in an 83-year-old man, which
      presented as a giant lesion in the posterior aspect of the right thigh, extending
      from the gluteal region proximally to the popliteal region distally. A
      multiloculated cystic mass was completely resected and histopathological
      examination confirmed the preoperative diagnosis. No local or systemic
      complications occurred postoperatively. The patient recovered fully at the end of
      postoperative 12 months.

PMID- 12510115
TI  - [A case of a ganglion cyst originating from the hip joint and surgical outcome].
AB  - Ganglion cysts are the most common soft tissue tumors of the hand, wrist, and
      foot. However, those originating from the hip joint are not so frequent. This
      case report presents a 36-year-old woman who complained of pain in the right
      groin. A diagnosis of atypical ganglion cyst of the hip was made and the lesion
      was surgically removed. The diagnosis was confirmed histopathologically. No
      complaints were observed after a follow-up period of 18 months.

PMID- 12510116
TI  - [Fibular transfer in a nine-week-old infant for complete congenital absence of
      the tibia].
AB  - The treatment of complete congenital absence of the tibia is controversial. The
      goal of the treatment is to construct a satisfactorily functioning knee joint,
      for which fibular transfer was described as an appropriate method. We performed
      reconstructive surgery using a modified Browns procedure in a nine-week-old boy
      with Jones type 1 congenital longitudinal deficiency of the tibia. In his final
      control at three years of age a good outcome was obtained according to the
      criteria by Epps et al. To our knowledge, this is the youngest patient to receive
      fibular transfer in the literature, to which we ascribed the satisfactory
      outcome.

PMID- 12510117
TI  - [Suprascapular nerve entrapment at the spinoglenoid notch secondary to a ganglion
      cyst].
AB  - Suprascapular neuropathy may occur as a result of traction, direct trauma,
      repetitive microtraumas, and extrinsic compression. A thirty-one-year-old man
      presented with non-traumatic complaints of right shoulder pain and stiffness.
      After exclusion of other causes associated with shoulder pain, a diagnosis of
      suprascapular nerve entrapment was considered. Electromyographic activity of the
      right shoulder was compared with that of the left side and involvement of the
      infraspinatus muscle was detected, with the supraspinatus muscle appearing
      normal. Magnetic resonance imaging revealed a ganglion cyst around the
      spinoglenoid notch. The patient underwent arthroscopic examination and open cyst
      excision. Arthroscopy did not show any labral tears. Pathological diagnosis was
      made as a cystic ganglion. On follow-up examinations, the patient's complaints
      disappeared and only minimal infraspinatus muscle atrophy was observed.
      Suprascapular nerve entrapment should be considered in the differential diagnosis
      of posterior shoulder pain.

PMID- 12510118
TI  - [Radiologic imaging modalities in foot and ankle disorders].

PMID- 12510119
TI  - [Ligament injuries of the ankle].

PMID- 12510120
TI  - [Soft tissue impingement syndromes of the ankle].

PMID- 12510121
TI  - [Osteochondral lesions of the talus].

PMID- 12510122
TI  - [Subtalar joint instability].

PMID- 12510123
TI  - [Achilles tendon diseases and its management].

PMID- 12510124
TI  - [Tarsal tunnel syndrome in sports].

PMID- 12510125
TI  - [Posterior tibial tendon dysfunction in athletes].

PMID- 12510126
TI  - [Heel pain in athletes].

PMID- 12510127
TI  - [Plantar fasciitis in athletes].

PMID- 12510128
TI  - [Morton's neuroma].

PMID- 12510129
TI  - [Comparison of four evaluation systems used for ankle injuries].
AB  - OBJECTIVES: Unlike the knee and shoulder, no widely accepted scoring system
      exists for the ankle joint. The aim of this study was to compare the results of
      diverse scoring systems used in ankle injuries. METHODS: We compared the results
      of four evaluation systems used for the ankle including those proposed by (i)
      Meislin et al. (ME), (ii) Martin et al. (MA), (iii) Kaikkonen and Kannus (KK) and
      (iv) a modified Bray's system (B). With the use of these evaluation systems we
      assessed the results of (i) 21 patients who underwent arthroscopic treatment for
      anterolateral impingement of the ankle, (ii) 17 patients who underwent surgical
      treatment for bimalleolar ankle fractures, and (iii) 22 patients receiving
      conservative treatment for grade 2-3 lateral ankle sprains. Statistical analyses
      were made using the chi-square test. RESULTS: The four scoring systems yielded
      similar results ranging from 23% to 33% in three groups, whereas conflicting
      results were obtained in the remaining cases (67% to 77%). The scores indicating
      poor outcomes were the highest with the ME and MA systems which included more
      subjective criteria. Similarly, the number of excellent results were
      significantly lower in these two systems than those of B and KK (p<0.001).
      CONCLUSION: Due to the high incidence of conflicting results between the scoring
      systems used, any particular patient may be rated as fair with one system and
      excellent with another. A standard ankle scoring system requires the inclusion of
      objective, subjective, and functional criteria, with each patient being evaluated
      according to individual activity levels as well.

PMID- 12510130
TI  - Electrocardiographic characteristics of ventricular arrhythmias arising from the
      aortic sinuses of valsalva: a case report and review of the literature.
AB  - We describe a patient with frequent, symptomatic, and drug-refractory premature
      ventricular contractions (PVCs) with a right bundle branch block, inferior axis
      morphology suggestive of a left ventricular outflow tract (LVOT) origin.
      Successful ablation of the PVCs was performed from the left coronary cusp of the
      aortic valve. We discuss our patient and review the literature regarding patients
      with ventricular arrhythmias arising from the coronary cusps, with special
      emphasis on the use of the electrocardiogram to aid localization of the focus.

PMID- 12510131
TI  - A streamlined "3-catheter" approach in the electrophysiological study and
      radiofrequency ablation of narrow complex tachycardia.
AB  - BACKGROUND: Electrophysiological study (EPS) followed by radiofrequency (RF)
      ablation has emerged as the treatment of choice for symptomatic narrow complex
      tachycardia (NCT), for which purpose, 5 catheters are typically used (4 for the
      initial EPS and an additional one for the subsequent RF ablation). We describe an
      alternative, streamlined approach using only 3 catheters [2 standard (diagnostic)
      and 1 deflectable, thermistor tip (mapping)] as the standard configuration for
      EPS and RF ablation in patients with NCT but no pre-excitation on ECG. METHODS
      AND RESULTS: Diagnosis was obtained in all 250 consecutive patients (mean age 45
      years, 174 females): atrio-ventricular nodal re-entrant tachycardia (AVNRT) in
      188 (75%), concealed accessory pathways (AP's) in 38 patients (15%), ectopic
      atrial tachycardia in 19 patients (8%), persistent junctional re-entrant
      tachycardia (PJRT) in 4 patients (2%) and atrial fibrillation in 1 patient. An
      additional diagnostic catheter was used for optimising atrial pacing in 3
      patients and for ventricular pacing in concealed right postero-septal AP's in
      another 3. An additional mapping catheter was used in 31 patients with concealed
      left-sided AP's, 2 with multiple AP's and 1 with PJRT. Three patients had
      complications (1 pulmonary embolism, 1 pericardial effusion and 1 atrio
      ventricular node block). Overall, the immediate success rate was 98% (224/229)
      with a recurrence rate of 4.4% (10/224), and the total success rate (with repeat
      RF ablation if necessary) was 99.2% (227/229) over a median follow-up period of
      31.4 months. The average cost saving was US$474 per procedure. Procedure duration
      (2.0 +/- 0.1 hours), fluoroscopy time (13 +/- 1 minutes) and the number of
      radiofrequency applications (5.4 +/- 0.3) also compared favourably with values
      reported in the literature for RF ablation of AVNRT. CONCLUSION: Compared to the
      conventional 5-catheter configuration for the combined EPS and RF ablation
      procedure in treatment of patients with NCT, the described 3-catheter
      configuration reduces cost, procedure duration and fluoroscopy time without
      compromising on success rate and safety. On these bases, we advocate its
      widespread adoption.

PMID- 12510132
TI  - Relationship between polarity of the flutter wave in the surface ECG and
      endocardial atrial activation sequence in patients with typical counterclockwise
      and clockwise atrial flutter.
AB  - BACKGROUND: The relation between ECG and activation patterns within atria in
      typical atrial flutter (AFL) patients (pts) has not been defined due to the lack
      of simultaneous multisite right and left atrial mapping. METHODS: In 13 pts with
      AFL, a Halo catheter was positioned along tricuspid annulus and multipolar
      catheters were placed in right atrial appendage, His bundle region, coronary
      sinus (CS), proximal portion of right pulmonary artery (Bachmann's bundle region,
      BB) and esophagus (Eso) to record right and left atrial activation
      simultaneously. RESULTS: In counterclockwise (CCW) AFL (11 pts), 9 showed
      negative flutter wave (F) and 2 positive F in the inferior leads. CCW/negative F;
      CS electrograms (EGs) were proximal to distal, Eso EGs were inferior to superior
      and BB activation was later than CS and Eso. positive F; BB activation was
      earlier than CS. Eso EGs were superior to inferior or simultaneous. In clockwise
      (CW) AFL (7 pts), 5 showed positive F and 2 negative F. CW/positive F; BB
      activation preceded Eso and CS. Eso EGs were superior to inferior. CS EGs were
      proximal to distal (1), middle to proximal, distal (3) or proximal, distal to
      middle (1). negative F; CS EGs were proximal to distal. CS activation was earlier
      than BB or CS and BB activation were simultaneous. Eso EGs were inferior to
      superior. CONCLUSION: Impulse conduction to the left atrial free wall through
      either lower or upper interatrial connection is a major determinant of ECG
      morphology in AFL.

PMID- 12510133
TI  - Recurrent atrial flutter and atrial fibrillation after catheter ablation of the
      cavotricuspid isthmus: a very long-term follow-up of 333 patients.
AB  - INTRODUCTION: Radiofrequency catheter ablation of the cavotricuspid isthmus is an
      effective therapy for typical atrial flutter (AFL), however, the long-term
      recurrence of AFL and early or late occurrence of atrial fibrillation (AF) are
      not well defined. This study investigated the long-term (up to 68 months) outcome
      of patients with typical AFL after catheter ablation of the cavotricuspid
      isthmus. METHODS: This study included 380 patients with typical AFL, who received
      linear ablation of the cavotricuspid isthmus. They were followed up at the
      outpatient clinic. A questionnaire was used to evaluate the symptoms suggestive
      of tachyarrhythmias, and 12-lead ECG, Holter monitoring and event recorders were
      used to confirm the diagnosis of tachyarrhythmias. RESULTS: At the end of study,
      47 patients lost follow-up, so that 333 patients were enrolled into final
      analysis. Ten (3%) patients had failed ablation of typical AFL. Univariate
      analysis showed that left atrial dimension was the only factor related to failed
      ablation. During the long-term follow-up period of 29 +/- 17 months (range 7 to
      68 months), 29 (9%) patients had recurrent AFL, including 15 with typical and 14
      with atypical AFL. Univariate and multivariate analyses showed that incomplete
      isthmus block and inducible atypical AFL were the independent predictors of
      recurrent typical and atypical AFL, respectively. One hundred and two (31%)
      patients developed AF, including 48 with early occurrence of AF (within 3 months
      after ablation), and 54 with late occurrence of AF (greater than 3 months).
      Univariate and multivariate analyses showed that prior history of AF and
      inducible AF were independent predictors of early occurrence of AF, and prior
      history of AF was the only independent predictor of late occurrence of AF.
      CONCLUSIONS: Linear ablation of the cavotricuspid isthmus is an effective therapy
      with low recurrence rate for patients with typical AFL. However, one-third
      patients had early or late occurrence of AF.

PMID- 12510134
TI  - Pulmonary vein bigeminy: electrophysiological characteristics and results of
      catheter ablation.
AB  - Pulmonary vein bigeminy is the pair of a second, late and ectopic pulmonary vein
      potential following atrial far-field activation and a first passive pulmonary
      vein potential during sinus rhythm. The aim of this study was to determine the
      electrophysiological characteristics of pulmonary vein bigeminy and to evaluate
      its relevance as a trigger for paroxysmal atrial fibrillation. METHODS AND
      RESULTS: Pulmonary vein bigeminy was recorded in 8 of 45 patients (18%) who
      underwent mapping of pulmonary veins for ablation of focal atrial fibrillation.
      The premature ectopic pulmonary vein potentials were conducted to the atria in 5
      patients and were not conducted (concealed bigeminy) in 3 patients. The coupling
      interval of the ectopic pulmonary vein potential to the preceding atrial signal
      during sinus rhythm was significantly longer in patients with conducted bigeminy
      (375 +/- 25 ms) than with concealed bigeminy (230 +/- 17 ms). The pulmonary vein
      bigeminy was driven by coronary sinus pacing with the pacing cycle length at
      lower stimulation rates and was suppressed by overdrive pacing. Coronary sinus
      pacing led to a separation of the first pulmonary vein potential from the atrial
      signal but the interval between the atrial signal and the second pulmonary vein
      potential remained unchanged. Focal ablation at the site of earliest ectopic
      pulmonary vein activity in 5 patients induced rapid repetitive firing before
      elimination of the pulmonary vein bigeminy. Ostial disconnection of the
      arrhythmogenic pulmonary vein in 3 patients was associated with elimination of
      the pulmonary vein bigeminy. During the follow-up of 9 +/- 5 months after
      ablation of the pulmonary vein bigeminy, 5 of the 8 patients (63%) were free of
      atrial fibrillation without antiarrhythmic medication. CONCLUSIONS: The response
      of pulmonary vein bigeminy to atrial pacing and ostial ablation suggests that
      pulmonary vein bigeminy depends on an intact electrophysiological breakthrough
      between the left atrium and the pulmonary vein. Ablation targeting the pulmonary
      vein bigeminy is a possible limited approach for this subgroup of patients with
      paroxysmal atrial fibrillation.

PMID- 12510135
TI  - Effect of radiofrequency catheter ablation of ventricular tachycardia on left
      ventricular function in patients with prior myocardial infarction.
AB  - INTRODUCTION: Successful RF ablation of VT late after MI can involve multiple
      applications and long lines of RF lesions. The impact on left ventricular
      function is potentially important, but not well defined. Quantitative
      echocardiography was used to determine the effect of radiofrequency (RF) ablation
      on left ventricular function in patients with ventricular tachycardia (VT) after
      myocardial infarction (MI). METHODS AND RESULTS: In 62 patients (55 men; age 67
      +/- 1.1 yr.) who underwent RF ablation for VT late after MI, left ventricular
      ejection fraction (LVEF) was quantified from digitized echocardiograms performed
      </=1 week before and <72 hours after ablation. Patients received a mean of 25.6
      +/- 2.2 (range of 3-98) RF lesions. The LVEF pre- and post-ablation did not
      differ for the group (pre-LVEF 29.8 +/- 11.9% vs. post-LVEF 29.5 +/- 11.2%, p =
      0.626), or for the 30 patients who received >25 RF lesions (Pre-LVEF 28.5 +/-
      11.1% vs. Post-LVEF 28.1 +/- 10.8%, p = 0.74) or for the 7 patients who received
      >40 RF lesions (Pre-LVEF 29.9 +/- 12.7% vs. Post-LVEF 29.2 +/- 6.2%, p = 0.84).
      Although LVEF did not change for the group, LVEF increased >5% in 12/62 (19.4%)
      pts and decreased >/=5% in 14/62 (22.5%) pts. Patients with a decrease in EF did
      not differ from the remaining patients with respect to age, gender, number of RF
      lesions, or use of a cooled RF catheter, but did have a better initial EF (38.8
      +/- 12.2% versus 27.2 +/- 10.6%, p = 0.001). CONCLUSION: Multiple RF ablation
      lesions confined to infarct regions do not measurably affect LV function, but a
      cautious approach, confining ablation lesions to areas of scar, as was attempted
      in this study, seems prudent.

PMID- 12510136
TI  - Left ventricular dysfunction is associated with prolonged average ventricular
      fibrillation cycle length in patients with implantable cardioverter
      defibrillators.
AB  - OBJECTIVES: In cellular studies, ventricular refractoriness (ERP) is prolonged in
      heart failure (CHF), but clinical evidence is lacking. The average ventricular
      fibrillation cycle length (VFCL) has been shown to correlate with local ERP. We
      hypothesized that the VFCL increases with left ventricular (LV) dysfunction.
      Therefore, we evaluated intracardiac VFCL recorded by implantable defibrillators
      (ICD) in patients with and without LV dysfunction. METHODS: We analyzed
      intracardiac VFCL recorded by sensing leads of Ventak MINI (Guidant) ICD in 49
      patients (35 men; age 54 +/- 13 years; 25 (51%) with coronary artery disease;
      mean LV ejection fraction (EF) 41 +/- 17%, range 76-10) from the European Ventak
      MINI Investigator Group. No patients were receiving antiarrhythmic drugs,
      including beta-blockers. Mean and median VFCL were obtained at predischarge
      testing during first charge time (4.5 +/- 2.7 s, range 1.4-11). RESULTS: Mean
      median VFCL was 186 +/- 21ms (range 150-230 ms). Patients with LVEF >/= 50% (n =
      14) had shorter median VFCL than patients with LVEF < 50% (n = 35), (171 +/- 14
      vs. 191 +/- 20 ms; p = 0.002). Median VFCL correlated with LVEF (r = -0.41; p =
      0.003) and age (r = 0.28, p = 0.04), but was not significantly associated with
      charge time and defibrillation threshold at implant. Similar results occurred
      with mean VFCL. In multiple linear regression and correlation models, only LVEF%
      was a significant predictor (p < 0.05 for all models) of median VFCL.
      CONCLUSIONS: LV dysfunction prolongs averaged VFCL in patients at risk for
      malignant ventricular arrhythmias who have implantable cardioverter
      defibrillators. This phenomenon might be related to alterations in the
      ventricular refractory period.

PMID- 12510137
TI  - Inappropriate shock delivery due to interference between a washing machine and an
      implantable cardioverter defibrillator.
AB  - Electromagnetic interference with implantable cardioverter defibrillators (ICD)
      can cause inappropriate delivery of therapies or temporary inhibition of ICD
      functions. The presented case describes electromagnetic interference between a
      washing machine and an ICD resulting in an inappropriate discharge of the device
      due to false detection of ventricular fibrillation.

PMID- 12510138
TI  - Trans-aortic His bundle ablation with permanent ventricular pacing via the
      coronary sinus in L-transposition of great arteries with classic Fontan
      procedure.
AB  - We report findings in a patient with 1-transposition of great arteries with
      single ventricle and classic Fontan procedure who required both His bundle
      ablation for palliation of refractory atrial tachycardia and placement of a
      transvenous dual-chamber atrio-ventricular permanent pacemaker for hemodynamic
      support. A method for retrograde trans-aortic His bundle ablation in this
      congenital anomaly and subsequent placement of permanent dual chamber pacemaker
      using the right atrium and coronary sinus as an access to the ventricle is
      described.

PMID- 12510139
TI  - Understanding medical practice: different outcomes of a pre-medical program.
AB  - This qualitative research study addresses the issue of how effective pre-medical
      programs are in preparing students for medical practice. Students nearing
      completion of a pre-medical program were interviewed and observed when consulting
      with patients in teaching hospitals, with the focus on how they understood and
      carried out medical practice. The study highlights significant differences in the
      outcome of the pre-medical program with respect to students' understanding of
      medical practice. Case studies are used to illustrate these differences. The
      results demonstrate that reaching a diagnosis and having a firm base in knowledge
      about symptoms and sicknesses are important to the students' understanding of
      medical practice. However, there are differences in the emphasis given to these
      issues and, more particularly, in the extent to which other aspects are taken
      into account. The students' understanding of medical practice range from
      something the doctor does to the patient's body to contributing to the person's
      health and life quality through cooperation and mutual respect. Implications for
      medical education arising from the study are addressed, underlining the need for
      a clear and explicit focus on developing students' understanding of medical
      practice throughout the pre-medical program.

PMID- 12510140
TI  - Interdisciplinary didactic instruction at academic health centers in the United
      States: attitudes and barriers.
AB  - Interdisciplinary care is a method of providing patient care through a team
      approach that incorporates the efforts of various health care providers. Studies
      show that this approach can improve patient care and decrease overall costs to
      the healthcare system. Despite the evidence for the benefits of interdisciplinary
      care, there are no well-defined models for training students during their
      didactic years to become members of an interdisciplinary team. This study
      utilized an investigator-developed questionnaire to determine the attitudes of
      administrators of professional schools in the USA toward interdisciplinary
      education, identified the perceived barriers to interdisciplinary education,
      examined the extent to which interdisciplinary education is occurring at academic
      health center campuses, and identified the courses that might best be taught in
      an interdisciplinary format. Administrators from medicine, nursing, and pharmacy
      hold positive attitudes toward interdisciplinary instruction. Respondents from
      nursing and pharmacy hold more favorable attitudes than their counterparts from
      medicine. Positive attitudes are seen more frequently among females than males,
      and among respondents from public single and multi-campuses than from private
      campuses. This study demonstrated that administrators espouse very positive
      attitudes toward interdisciplinary education, although they perceive the barriers
      to interdisciplinary education and the courses most suited for an
      interdisciplinary approach differently. More discussions among administrators of
      various disciplines may allow barriers to be overcome and allow development of
      interdisciplinary didactic courses that could test the hypothesis that these
      courses are more cost effective and more likely to foster interdisciplinary
      teamwork in the clinical setting.

PMID- 12510141
TI  - Predictive validity of the Medical College Admissions Test Writing Sample for the
      United States medical licensing examination steps 1 and 2.
AB  - Despite the amount of published research on the predictive validity of the
      Medical College Admissions Test (MCAT) taken as a whole, few published reports
      separate the individual predictive validity of the Writing Sample. The purpose of
      this study is to provide data on the predictive validity of the Writing Sample
      for the national licensing exam used in the United States. Subjects consisted of
      1992-1995 matriculants from a publicly owned medical school in the Southeastern
      United States. Independent variables were undergraduate grade point average, and
      four section scores on a required admissions test (Biological Sciences, Physical
      Sciences, Verbal Reasoning, and Writing Sample). The dependent variables were
      Steps 1 and 2 on the three step licensing examination. Steps 1 and 2 of the
      examination are taken during medical school. Multiple regression models
      calculated additional variance accounted for by the addition of the Writing
      Sample to a model containing grade point average and the other admissions test
      section scores. In multivariate analyses, when grade point average and all
      admissions test scores were considered as predictors of licensing exam scores,
      the Writing Sample variable did not add to the ability to predicting the Step 1
      or Step 2 scores. The results of this study suggest that the Writing Sample has
      limited predictive validity for assessing success on a national licensing exam.
      However, as others suggest, the value of the Writing Sample and other surrogates
      of communication probably lie in predicting performance in the clinical years of
      medical school and beyond. Additional work should include evaluating the
      predictive validity of the Writing Sample and other pre-medical school measures
      of communication with widely acceptable measures of performance in clinical
      settings, including physician-patient communication.

PMID- 12510142
TI  - Student perspectives on critical incidents in the tutorial group.
AB  - The aim of this study is to explore student's perceptions of incidents in
      tutorial groups and their perceptions of the tutor's role in these incidents.
      This study investigated the differences between three types of perceptions: the
      perceptions of the occurrence of critical incidents in tutorial groups, the
      perceptions of whether these incidents inhibit tutorial group functioning and the
      expectations students have of the role of the tutor with respect to these
      incidents. Variations in these student perceptions were also investigated for
      different training levels. The subjects consisted of a stratified random sample
      of 200 students from first, second, third and fourth year at the Medical School
      of the University of Maastricht. We used a questionnaire that consisted of a list
      of 36 statements and related descriptions of critical incidents in the tutorial
      group. Six potential success inhibitors (lack of elaboration, lack of
      interaction, unequal participation, lack of cohesion, difficult personalities and
      lack of motivation) were assumed to underlie the statements of the questionnaire.
      Students were asked to rate each incident on a five-point Likert scale for the
      three types of perceptions. The major finding of this study was that there are
      significant differences between the three types of student perceptions. We also
      found that there are significant differences between perceptions of students in
      each of the four academic years. We conclude that all potential success
      inhibitors play a role in explaining dysfunctional tutorial groups. Motivational
      influences seem to have a particularly strong impact on tutorial group function.

PMID- 12510143
TI  - Introducing professional educators into academic medicine: stories of exemplars.
AB  - This article describes an oral history project aimed at documenting the history
      and contributions of the innovation of hiring professional educators in medical
      schools to improve the education of medical students, residents, and fellows. Six
      professional educators who spent their careers in medical schools were chosen as
      Exemplars: Stephen Abrahamson, Ph.D.; Charles Dohner, Ph.D.; Arthur Elstein,
      Ph.D.; Hilliard Jason, M.D., Ph.D.; Christine McGuire, M.A.; and Frank Stritter,
      Ph.D. Pairs of senior professional educators currently working in medical schools
      interviewed the six Exemplars using a standardized protocol. Articles describing
      each Exemplar appear consecutively in this and subsequent issues of Advances in
      Health Professions Education. The series culminates with an article that presents
      the consensus conclusions of the series authors, based on the five study
      questions that guided the study and interview protocol.

PMID- 12510144
TI  - Stephen Abrahamson, PhD, ScD, educationist: a stranger in a kind of paradise.
AB  - This profile of Stephen Abrahamson, Ph.D., Sc.D., is the first of six profiles to
      appear as part of the Exemplar project focused of six retired medical educators
      who transformed the field of medical education. The exemplars, all graduate
      degree recipients in education were interviewed by six senior present-day medical
      educators using a common protocol designed to elicit career chronology and the
      significant contributions of educationists to medical education of Dr.
      Abrahamson's profile was based on an in-depth two-day interview, examination of a
      comprehensive list of his publications, the history of the Society of the
      Directors of Research in Medical Education, and unsolicited conversations with
      several of his colleagues. Dr. Abrahamson began his career teaching high school,
      later receiving a masters and doctorate degrees, in preparation for a career as a
      teacher-educator. Through collaboration with Dr. George Miller, Dr. Abrahamson
      began his career as an educationist in medicine - one who studies the education
      process and prepares others to become teachers - by teaching medical school
      faculty about the science of education. Dr. Abrahamson's career was devoted to
      applying his evidence-based education approach to the newly emerging profession
      of medical education. An examination of his career shows that he made four vital
      contributions to medical education - defining the educationist role, serving as a
      teaching/mentor/network builder/friend to medical educators, curriculum change
      agent and innovator at USC, and demonstrating and articulating the value of
      offices of medical education and research in medical education. More broadly, Dr.
      Abrahamson identified three major contributions made by educationists to the
      field of medical education: the application of education principles to
      instructional/assessment innovations (e.g., programmed patients), an evidence
      based approach to assessing education, and faculty development/teacher training.
      Based on his half-century of experience in medical education, Dr. Abrahamson
      outlined seven lessons for success as an educationist in medicine.

PMID- 12510145
TI  - Threats to the validity of locally developed multiple-choice tests in medical
      education: construct-irrelevant variance and construct underrepresentation.
AB  - Construct-irrelevant variance (CIV) - the erroneous inflation or deflation of
      test scores due to certain types of uncontrolled or systematic measurement error 
      and construct underrepresentation (CUR) - the under-sampling of the achievement
      domain - are discussed as threats to the meaningful interpretation of scores from
      objective tests developed for local medical education use. Several sources of CIV
      and CUR are discussed and remedies are suggested. Test score inflation or
      deflation, due to the systematic measurement error introduced by CIV, may result
      from poorly crafted test questions, insecure test questions and other types of
      test irregularities, testwiseness, guessing, and test item bias. Using
      indefensible passing standards can interact with test scores to produce CIV.
      Sources of content underrepresentation are associated with tests that are too
      short to support legitimate inferences to the domain and which are composed of
      trivial questions written at low-levels of the cognitive domain. "Teaching to the
      test" is another frequent contributor to CUR in examinations used in medical
      education. Most sources of CIV and CUR can be controlled or eliminated from the
      tests used at all levels of medical education, given proper training and support
      of the faculty who create these important examinations.

PMID- 12510146
TI  - Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and
      inhibition of neuronal regeneration.
AB  - ASY, also designated Nogo, RTN-X, or RTN4, is a reticulon family protein
      containing two transmembrane domains and a C-terminal double lysine endoplasmic
      reticulum (ER) retrieval motif. Three protein variants are synthesized from the
      cognate mRNAs produced by alternative splicing, and are expressed in almost all
      tissues, localizing predominantly in the ER. The ASY protein induces apoptosis in
      various cancer cells when overexpressed, whereas normal cells are relatively
      resistant to ASY-dependent apoptosis. Furthermore, transcription of this gene is
      suppressed in certain types of cancers, suggesting that ASY may act to suppress
      tumor development. Although the physiological function of this protein has not
      been well defined, Nogo-A protein, the large variant of ASY, has been shown to
      inhibit neuronal regeneration in the central nervous system. Therefore, the
      products of this gene may be multi-functional, regulating apoptosis, tumor
      development, and neuronal regeneration.

PMID- 12510147
TI  - Roles of the stress-induced gene IEX-1 in regulation of cell death and
      oncogenesis.
AB  - In response to changes in the external environment cells must initiate a
      coordinated program of gene expression for them to adapt. IEX-1 (immediate early
      response gene X-1) is precisely regulated by multiple transcription factors among
      which p53, NF-kappaB/rel, Sp1 and c-Myc play central roles, to ensure rapid and
      transient expression of IEX-1 in cells under a variety of stress conditions.
      Overexpression of IEX-1 renders some cells sensitive to apoptosis and accelerates
      cell cycle progression, but reduces proliferation of other cells, whereas
      disruption of IEX-1 expression is associated with decreases in both apoptosis and
      cell cycle progression. In sharp contrast to in vitro studies, in vivo
      constitutive expression of IEX-1 prevents activated T cells but not B cells from
      apoptosis, as shown using IEX-1-transgenic mice that target IEX-1 expression
      specifically to lymphocytes driven by the Emu enhancer. The animals developed a
      lupus-like disease and subsequently a high incidence of T cell lymphomas when
      they aged, due to insufficient apoptosis of T cells. These varied effects of IEX
      1 on cell death and cell cycle progression in a cell-context dependent fashion
      implicate that IEX-1 is involved in more than one signaling pathway,
      understanding of which will certainly improve our knowledge with respect to
      cancer biology, cell death and cell cycle regulation.

PMID- 12510148
TI  - Regulation of cell apoptosis by protein kinase c delta.
AB  - The isoforms of the PKC family are activated in response to mitogenic stimuli, to
      inflammatory stimuli, and to stress and play important roles in a variety of
      cellular functions including apoptosis. PKCdelta a member of the novel PKC
      subfamily, is actively involved in cell apoptosis in a stimulus and tissue
      specific manner; it both regulates the expression and function of apoptotic
      related proteins and is itself a target for caspases. Activation of PKCdelta by
      various apoptotic stimuli results in the translocation of PKCdelta to distinct
      cellular compartments such as mitochondria, golgi and nucleus, and the
      differential translocation contributes to its different effects. In addition,
      phosphorylation of PKCdelta on distinct tyrosine residues and its association
      with specific apoptotic related proteins such as c-Abl, DNA-PK, p73 and lamin B
      are pivotal to its function in cell apoptosis. Recent findings on these aspects
      of the PKCdelta cascades are the major focus of this review.

PMID- 12510149
TI  - BCL-2 in prostate cancer: a minireview.
AB  - Prostate cancer progression and the development of androgen-independent prostate
      cancer have been largely related to a number of genetic abnormality that affect
      not only the androgen receptor but also crucial molecules involved in the
      regulation of survival or apoptotic pathways. One of these molecules, the pro
      survival protein BCL-2, has been associated with the development of androgen
      independent prostate cancer due to its high levels of expression in androgen
      independent tumors in advanced stages of the pathology. The upregulation of BCL-2
      after androgen ablation in prostate carcinoma cell lines and in a castrated-male
      rat model further established a connection between BCL-2 expression and prostate
      cancer progression. This review focuses on the experimental evidence that
      associates BCL-2 expression with prostate carcinogenesis and cancer progression,
      and analyzes the evidence that links the phosphatidylinositol 3-kinase (PI 3
      kinase)/nuclear factor kappa B (NF-kappaB) survival pathway with the upregulation
      of BCL-2. The way in which hormone ablation influences this survival pathway and
      the potential application of novel therapeutic strategies to overcome this anti
      apoptotic mechanism is examined.

PMID- 12510150
TI  - CSE1L/CAS: its role in proliferation and apoptosis.
AB  - CAS/CSE1L is the human homologue of the yeast gene CSE1. It was first cloned
      while searching for genes that rendered breast cancer cells resistant towards
      toxin induced apoptosis. Since depletion of CSE1 leads to cell-cycle arrest, CAS
      is thought to be involved in proliferation. CAS functions in the mitotic spindle
      checkpoint. CAS is located on chromosome 20q13, a locus often amplified in
      cancers of various origin, e.g. colonic or breast cancer. Since genetic
      instability is a hallmark of cancer, amplification or over expression of the CAS
      gene might interfere with or override its role in the mitotic spindle checkpoint.
      CAS is also implicated in the nuclear to cytoplasmic reshuffling of importin
      alpha, which itself is necessary for the nuclear transport of several
      proliferation activating proteins, transcription factors, oncogene and tumor
      suppressor gene products such as p53 and BRCA1. Inhibition of MEK1 mediated
      phosphorylation has been shown to enhance paclitaxel (Taxol) induced apoptosis in
      breast, ovarian, and lung tumor cell lines in-vitro. Since CAS is also
      phosphorylated (activated) by MEK1, and since the anti-cancer drug Taxol alters
      the microtubule assembly and activates pro-apoptotic signaling pathways, altering
      the activity/phosphorylation status of CAS via MEK1 inhibition may present a
      potential strategy in experimental cancer therapy.

PMID- 12510151
TI  - Differential regulation of cell survival by CD40.
AB  - The CD40 cell surface receptor is required for normal function of the immune
      system and is a positive regulator of cell survival for normal B-lymphocytes.
      However, there is evidence to support both pro- and anti-apoptotic functions for
      CD40 in malignant B-cells and epithelial cancers. There is increasing interest in
      the potential of CD40 activating agents as novel therapies for cancer and it is
      essential to understand the differential response of malignant cells, to inform
      the design of trials. Here we review the current understanding of differential
      responses to CD40 activation and apoptosis controlling proteins regulated by CD40
      that might account for these effects.

PMID- 12510152
TI  - Apoptotic action of estrogen.
AB  - Estrogen as a mitogen stimulates cell proliferation and prevents cell death in
      many cell types. In patients, estrogen is known to stimulate breast and uterus
      cancer development. Ironically, high doses of estrogen can induce regression of
      hormone-dependent breast cancer in postmenopausal women. The comprehensive
      mechanism by which estrogen induces tumor recession in breast cancer is still
      unknown, but activation of the Fas/FasL pathways plays a key role in this
      process. Laboratory studies show that the apoptotic action of estrogen is the
      major factor leading to cell number decreases in several cell types. The effects
      of estrogen are estrogen-receptor dependent. In this mini review, we will focus
      on the latest findings regarding estrogen apoptotic effects in several cell
      models, including breast cancer cells, and summarize the possible mechanisms
      involved in these estrogen mediated processes. New potential implications for the
      pharmacological control of breast cancer with estrogen in post-menopausal women
      are also discussed.

PMID- 12510153
TI  - On the role of Hsp27 in regulating apoptosis.
AB  - Heat shock proteins (Hsps) comprise several different families of proteins that
      are induced in response to a wide variety of physiological and environmental
      insults. One such protein which is highly induced during the stress response is a
      27-kDa protein, termed Hsp27 whose expression is seen to correlate with increased
      survival in response to cytotoxic stimuli. It has been shown to prevent cell
      death by a wide variety of agents that cause apoptosis. Hsp27 is a molecular
      chaperone with an ability to interact with a large number of proteins. Recent
      evidence has shown that Hsp27 regulates apoptosis through an ability to interact
      with key components of the apoptotic signalling pathway, in particular, those
      involved in caspase activation and apoptosis. This article will review recent
      advances in the field and will address some of the potential mechanisms by which
      Hsp27 functions as an anti-apoptotic molecule.

PMID- 12510154
TI  - Upregulation of survivin by HIV-1 Vpr.
AB  - The human survivin gene belongs to the family of inhibitor of apoptosis proteins
      (IAP) and is involved in apoptosis inhibition and regulation of cell division.
      The survivin gene is the only member of the IAP family whose expression is known
      to be regulated through the cell cycle. Survivin expression reaches the highest
      levels during the G(2)/M transition and then is rapidly degraded during the G(1)
      phase. Here we report that the human immunodeficiency virus type 1 (HIV-1)
      upregulates Survivin expression via survivin promoter transactivation. Vpr, an
      HIV-1 accessory protein that induces cell cycle arrest in G(2)/M, is necessary
      and sufficient for this effect. Blocking Vpr-induced G(2)/M arrest leads to
      elimination of the survivin promoter transactivation by Vpr. Our results suggest
      that Survivin may be actively involved in regulating cell viability during HIV-1
      infection.

PMID- 12510155
TI  - Splenic lymphocytes of adult Xenopus respond differentially to PMA in vitro by
      either dying or dividing: significance for cancer resistance in this species.
AB  - Wild-type populations of amphibians, unlike mammalians, appear to be resistant to
      spontaneous and chemically induced neoplasms. Few true cancers have been reported
      for non-isogeneic members of Xenopus laevis, despite their widespread use in
      laboratories around the world. Injection of even the most powerful direct
      mammalian oncogens e.g. N-methyl N-nitrosourea, that depleted specific
      populations of T lymphocytes, did not induce cancer. Phorbol diesters, e.g. PMA,
      are mitogens and apoptogens in both amphibian, and mammalian immunocytes. In
      mammalian cells, regulation of the cell cycle and of apoptosis are often
      intimately linked, however, a disjunction in time between early apoptosis and
      later cell cycling, has been observed with PMA-treated Xenopus splenocytes. Thus,
      a particular difference between amphibians and mammals may be the requirement to
      enter the cell cycle before a progression to death by apoptosis. This hypothesis
      was tested here using dual staining flow cytometry. Xenopus laevis splenocytes
      were cultured for 8, 24 and 48 hours with phorbol 12-myristate 13-acetate (PMA),
      previously shown to be mitogenic and apoptotic with mature Xenopus lymphocytes.
      The cells were stained with FITC-conjugated Annexin V or with FITC-labeled
      deoxyuridine triphosphates (FITC-dUTP) to assay for the apoptotic markers
      phosphotidylserine or DNA strand breaks respectively. Phycoerythrin (PE)
      conjugated anti-human proliferating cell nuclear antigen (PE-PCNA) was used as a
      cell cycle marker that is present during the entire cell cycle. Propidium iodide
      (PI) binds DNA and was used to assay for late stage apoptosis, as well as to
      assess DNA content. Significantly higher levels of apoptosis develop rapidly in
      PMA-exposed splenocytes and are maintained at 24 hours, declining by 48 hours.
      Cells expressing PCNA or incorporating PI in excess of the normal genomic level
      were found by 48 hours following PMA exposure. The absence of any significant
      rise in a small (<5%) dual staining cell population indicates that the apoptotic
      cell population remained distinct from cells already in the cell cycle from the
      onset of PMA exposure. Thus, Xenopus splenocytes respond differentially to PMA.
      Those that undergo apoptosis rapidly were quiescent, non-cycling small
      lymphocytes. Moreover, the cells that eventually begin division, following PMA
      exposure, were unaffected by the early apoptosis and do not themselves die while
      in the cell cycle. The rapid apoptotic response of X. laevis cells to PMA may
      confer a natural cancer resistance in this species, as cells that fail to enter
      the cell cycle after exposure to cancer promoting reagents cannot express genetic
      destabilization that might have led to transformation.

PMID- 12510156
TI  - Oxidative stress-induced apoptosis in dividing fibroblasts involves activation of
      p38 MAP kinase and over-expression of Bax: resistance of quiescent cells to
      oxidative stress.
AB  - Oxidative stress has been postulated to be involved in aging and age-related
      degenerative diseases. Cell death as a result of oxidative stress plays an
      important role in the age related diseases. Using human diploid fibroblasts (HDF)
      as model to study the mechanism of cell death induced by oxidative stress, a
      condition was standardized to induce apoptosis in the early passage sub-confluent
      HDFs by a brief exposure of cells to 250 microM hydrogen peroxide. It was
      observed that p38 MAP kinase (MAPK) was activated soon after the treatment
      followed by over-expression of Bax protein in cells undergoing apoptosis. An
      interesting finding of the present study is that the confluent, quiescent HDFs
      were resistant to cell death under identical condition of oxidative stress. The
      contact-inhibited quiescent HDFs exhibited increased glutathione level following
      H(2)O(2)-treatment, did not activate p38 MAP kinase, or over-express Bax, and
      were resistant to cell death. These findings indicated that there was a
      correlation between the cell cycle and sensitivity to oxidative stress. This is
      the first report to our knowledge that describes a relationship between the
      quiescence state and anti-oxidative defense. Furthermore, our results also
      suggest that the p38MAPK activation-Bax expression pathway might be involved in
      apoptosis induced by oxidative stress.

PMID- 12510157
TI  - Cisplatin-induced pulse of germ cell apoptosis precedes long-term elevated
      apoptotic rates in C57/BL/6 mouse testis.
AB  - Chemotherapeutic doses of cisplatin impair spermatogenesis and ultimately cause
      azoospermia and infertility in some men. The mechanism by which cisplatin damages
      testicular germ cells is poorly understood. Cisplatin's impact is first detected
      hours after exposure in the formation of DNA cross-links followed by weeks of
      testicular damage. Here, we report in 11-week-old male mice an early and massive
      rise of germ cell apoptosis after a single intraperitoneal (i.p.) injection of
      either 5 or 10 mg/kg cisplatin. For the lower dose, a roughly 9-fold peak
      increase in the apoptotic index over the control level is observed at 36 h, and
      for the higher dose, a 24-fold rise is seen at 24 h. At these peak levels, the
      lower dose produced a higher ratio of apoptotic early spermatocytes to apoptotic
      spermatogonia than did the higher dose. In addition to this early wave of germ
      cell die-off, our data show that while the post-wave apoptotic rates for both
      dose regimes diminish, at 12 days the apoptotic rates appear significantly higher
      (5 mg/kg) than controls. In summary, our findings show two events set in motion
      by acute cisplatin exposure: (1) a previously unreported massive apoptotic die
      off of germ cells followed by (2) an elevated apoptotic rate possibly reflecting
      long-term or permanent damage to the seminiferous tubule.

PMID- 12510160
TI  - On the systematic position of Ophiosacculus Macy, 1935 (digenea:
      Lecithodendriidae), with the erection of the Ophiosacculinae n. subfam.
AB  - The phylogenetic relationships and systematic position of the digenean genus
      Ophiosacculus Macy, 1935 has been controversial and opinions of different authors
      on its systematic position and content are contradictory. Molecular analysis
      based on the partial sequences of the large subunit ribosomal DNA gene of the
      type and only valid species of the genus, Ophiosacculus mehelyi (Modlinger,
      1930), as well as previously published sequences of members of several families
      of Plagiorchiata (including the Allassogonoporidae, Lecithodendriidae and
      Pleurogenidae as potential relatives of Ophiosacculus) has shown that
      Ophiosacculus forms a clade with the typical representatives of the
      Lecithodendriidae from bats. Ophiosacculus is basal to the cluster containing
      Lecithodendrium, Prosthodendrium and Pycnoporus and has quite pronounced
      differences in the sequenced fragment compared to these genera. Based on the
      results of the molecular study, morphological characteristics of Ophiosacculus
      (in particular, possession of a seminal vesicle lying freely in parenchyma) and
      the fact that the type-specimen of Gyrabascus brevigastrus Macy, 1835 (type
      species of the monotypic genus Gyrabascus and type-genus of the subfamily
      Gyrabascinae) belongs to Allassogonoporus, a new subfamily, the Ophiosacculinae,
      with Ophiosacculus as the type-genus, is established within the
      Lecithodendriidae. Molecular study did not support a close phylogenetic
      relationship between Allassogonoporus and Ophiosacculus, although several authors
      previously allocated both these genera to the Allassogonoporidae. Morphological
      study revealed the position of the genital pore in O. mehelyi to be at the
      posterior margin of the ventral sucker. An amended diagnosis of Ophiosacculus and
      a diagnosis of Ophiosacculinae n. subfam. are given.

PMID- 12510161
TI  - Proleptus obtusus Dujardin, 1845 (Nematoda: Physalopteridae) from the puffadder
      shyshark Haploblepharus edwardsii (Scyliorhinidae) from off South Africa.
AB  - Specimens of the physalopterid nematode Proleptus obtusus Dujardin, 1845
      collected from the intestine of the puffadder shyshark Haploblepharus edwardsii
      (Voigt) off De Hoop Nature Reserve, Cape Province, South Africa, made possible
      the redescription this little-known species. The SEM study of the cephalic end
      revealed the presence of circumoral denticles and some oral structures (lateral
      transverse mounds on the inner surface of pseudolabia, dorsolateral and
      ventrolateral band-like formations or lamellae surrounding the buccal cavity) not
      previously reported for any species of Proleptus. The shape of the tip of the
      right spicule is considered to be the only reliable feature for differentiating
      P. obtusus from the closely related P. acutus Dujardin, 1845. The finding of the
      former in H. edwardsii represents a new host record.

PMID- 12510162
TI  - Cercaria sevillana n sp, a new cercaria (Digenea: Microphallidae) from Nassarius
      reticulatus (L) (Mollusca: Prosobranchia) in Portugal.
AB  - Cercaria sevillana n. sp. (Digenea: Microphallidae) was discovered infecting the
      gonads and digestive gland of the prosobranch Nassarius reticulatus (L.)
      (Nassariidae) collected from the Ria de Aveiro, Portugal. Cercariae were obtained
      by natural emission and were studied under a differential interference contrast
      microscope and scanning electron microscope (SEM). C. sevillana n. sp. is
      identical to the cercaria found by Dolgikh (1965) in the same mollusc host from
      the Black Sea, but erroneously named C. misenensis Palombi, 1940, which is a
      parasite of Cerithium rupestre Risso, 1826 (Cerithiidae). Cercaria sevillana n.
      sp. can be distinguished from C. misenensis by its tail being shorter than the
      cercarial body, as well as by differences in the pattern of penetration glands
      the size and shape of the stylet and excretory vesicle, and its behavioural
      pattern. An unusual structure of the tail of this new cercaria was observed by
      SEM; it is characterised by the presence of annular folded membranes arranged as
      overlapping flounces around its central axis. This resembles the traditional
      skirts of the women of Seville. Such a morphological feature of the tail has not
      been previously observed, but may be a feature of many microphallid cercariae.

PMID- 12510163
TI  - Nomimoscolex semenasae n sp (proteocephalidea: Monticelliidae), a cestode
      parasite of Diplomystes viedmensis (Pisces: Siluriformes) from the Patagonian
      region of Argentina.
AB  - Nomimoscolex semenasae n. sp. is described from the primitive fish Diplomystes
      viedmensis (Siluriformes) from the Patagonian region of Argentina. The new
      species is placed in Nomimoscolex because of the cortical position of the
      vitelline follicles, medullary position of the testes, ovary and uterus, and
      having a scolex with four uniloculate suckers. N. semenasae differs from all
      other species in the genus by the following combination of characters: (1.apical
      organ absent; (2). strobila acraspedote; (3). vagina anterior or posterior to
      cirrus-sac and lacking a sphincter; (4). testes in one irregular layer and in two
      fields connected anteriorly; (5). uterine stem cortical in immature proglottides,
      growing from cortical stem into medullary region in mature proglottides; (6).
      long uteroduct; and (7). presence of spiniform microtriches on all regions of the
      scolex, proliferation zone and immature proglottis. This is the first record of a
      proteocephalidean tapeworm in D. viedmensis and in the family Diplomystidae.

PMID- 12510164
TI  - The Buproridae Thorell, 1859, a family of ascidicolous copepods (Copepoda:
      Cyclopoida).
AB  - The adult female of Buprorus loveni Thorell, 1859, a cyclopoid copepod inhabiting
      the branchial cavities of solitary ascidians, is redescribed in detail from new
      material collected in Scandinavian waters and from the southern part of the North
      Atlantic off Mauritania. The antennal segmentation pattern exhibited by all seven
      subfamilies of the family Ascidicolidae Thorell, 1860 is compared. The
      segmentation of the Buprorinae is different from that of all other subfamilies
      within the ascidicolid series. It is concluded that the antenna of Buprorus is
      not an appropriate model for interpreting the segmentation of other ascidicolids
      because the Buprorinae is the only subfamily in which the first and second
      endopodal segments are primitively fused and the third is distinct. The
      Buproridae Thorell, 1859 is here treated as a separate family within the
      Cyclopoida.

PMID- 12510165
TI  - Redescription of Perezitrema bychowskyi (Caballero & Caballero, 1975) (Trematoda:
      Macroderoididae), with remarks on the systematic status of Perezitrema Barus &
      Moravec, 1996.
AB  - A description is given of Perezitrema bychowskyi (Caballero & Caballero, 1975)
      based on newly collected specimens from the intestine of the tropical gar
      Atractosteus tropicus Gill in the Pantalos de Centla Biological Reserve, State of
      Tabasco, southeastern Mexico, collected in April 2001, and on a re-examination of
      the type-specimens. In contrast to the original description, the excretory
      vesicle of P. bychowskyi was found to be elongate saccular and the intestinal
      caeca join near the posterior extremity and open via a common median anus. These
      features, and the presence of a cirrus-sac, were found, using differential
      interference contrast optics in the type-specimens of P. viguerasi Barus &
      Moravec, 1967, the type-species of the genus. This made possible a re-diagnosis
      of Perezitrema Barus & Moravec, 1967. Although P. bychowskyi is very similar to
      P. viguerasi and their conspecificity cannot be excluded, the poor condition of
      the type-specimens of the latter does not enable their detailed comparison and,
      consequently, both are considered independent species for the time being. P.
      lepisostei (Watson, 1976) is considered a junior synonym of P. bychowskyi.
      Perezitrema is provisionally placed in the plagiorchioid family Macroderoididae,
      even though some of its morphological features are similar to those of the
      lepocreadioid families Enenteridae and Lepocreadiidae.

PMID- 12510166
TI  - Cycle evolutif de Bucephalus anguillae Spakulova, Macko, Berrilli & Dezfuli, 2002
      (Digenea, Bucephalidae) parasite de Anguilla anguilla (L.).
AB  - The species of Bucephalus from the eel Anguilla anguilla of the north-eastern
      Tunisian lagoons was identified as B. anguillae which was recently described by
      Spakulova et al. (2002) from the Adriatic coast of Italy. In order to confirm
      that this eel digenean is distinct from B. polymorphus von Baer, 1827 present in
      other freshwater fishes, we investigated the life-cycle of this species. Surveys
      in the wild and experimental studies have shown that the life-cycle of B.
      anguillae is completed in brackish environments, with the lamellibranch Abra
      tenuis as the first intermediate host and the cyprinodontid fish Aphanius
      fasciatus as the second intermediate host. This life-cycle differs from that of
      B. polymorphus and can be considered as an additional argument for the
      distinction of these two morphologically similar species.

PMID- 12510167
TI  - A revision of Microbothriorhynchus Yamaguti, 1952 (Cestoda: Trypanorhyncha), with
      the redescription of M coelorhynchi Yamaguti, 1952 and the description of M
      reimeri n sp.
AB  - The genus Microbothriorhynchus Yamaguti, 1952 is revised. Plerocerci of M.
      coelorhynchi Yamaguti, 1952 from the body-cavity of Brotula barbata (Bloch &
      Schneider) off the Angolan coast are re-described, and M. reimeri n. sp. from the
      body-cavity of Helicolenus maculatus (Cuvier) and Caelorinchus parallelus
      (Gunther) from coastal waters off Mozambique is added to the genus. Both species
      are characterised in having an elongated, slightly craspedote scolex with small,
      collar-like bothridia, an elongate pars vaginalis and very long bulbs. The
      tentacular armature is heteroacanthous atypica, with eight principal hooks and
      intercalary hooks merging with a band of spiniform hooks on the external tentacle
      surface. The adult is unknown. Microbothriorhynchus is allocated to the
      Lacistorhynchidae Guiart, 1927, in having a blastocyst, two bothridia and a
      heteroacanthous atypica armature. Dasyrhynchus Pintner, 1928 and Pseudogrillotia
      Dollfus, 1969 are considered the most closely related genera, sharing characters
      such as the craspedote scolex, similar scolex proportions and hook patterns.
      Microbothriorhynchus appears to link the heteroacanthous atypica genera Grillotia
      Guiart, 1927 and Pseudogrillotia with the poeciloacanthous genus Dasyrhynchus.

PMID- 12510168
TI  - Thaumamermis zealandica n sp (Mermithidae: Nematoda) parasitising the intertidal
      marine amphipod Talorchestia quoyana (Talitridae: Amphipoda) in New Zealand, with
      a summary of mermithids infecting amphipods.
AB  - A new nematode, Thaumamermis zealandica n. sp. (Mermithidae; Nematoda), is
      described parasitising the intertidal marine amphipod Talorchestia quoyana Milne
      Edwards (Talitridae) from the coast of South Island, New Zealand. The new species
      is characterised by the degree of dimorphism of the spicules, the arrangement of
      the genital papillae, the shape and length of the vagina and the anteriorly
      placed amphids. This is the first known marine host of a member of the family
      Mermithidae. Published records of mermithid nematodes from amphipods are
      presented.

PMID- 12510171
TI  - Aging of myocardial collagen.
AB  - The objective of this article was to present a review of the collagen tissue of
      the heart muscle as a function of age. The myocardial collagen matrix consists of
      a network of fibrillar collagen which is intimately connected to the myocyte.
      Most collagen fibers reside in parallel with myocytes. These fibers may have a
      wavy, taut or coiled appearance. Fibrillar collagen types I and III are the major
      components of the myocardial collagen matrix. Collagen type I has been found to
      represent nearly 80% of the total collagen protein, while type III collagen is
      present in lower proportions (approximately 11%). Cardiac fibroblasts are the
      cellular source of fibrillar collagen, cardiac myocytes expressing only mRNA for
      type IV collagen. Collagens types I and III exhibit a high tensile strength which
      plays an important role in the behavior of the ventricle during the cardiac
      cycle. The collagen concentration and the intermolecular cross-linking of
      collagen increase with age. Measurements of collagen content in myocardial tissue
      suggest that it is the type I collagen fibers that increase in number and
      thickness in the aged. At the same time, electron microscopic observations have
      shown an increase in the number of collagen fibrils with a large diameter in the
      aging heart. The mechanism responsible for the myocardial fibrosis in the
      senescent myocardium is unclear. The collagen deposition in the myocardium could
      be due to the regulation of collagen biosynthesis at pre-translational levels. It
      is possible that the regulatory elements involved in this process are growth
      factors such as TGF-beta 1 and hormones and neurotransmitters. Details of
      regulatory mechanism that may come into play during aging may be elucidated by
      further investigations. The accumulation of collagen within the myocardium
      increases muscle stiffness. Myocardial function is affected by this process; this
      is usually reflected by incomplete relaxation during early diastolic filling, and
      presumably account for the decrease in early left ventricular diastolic
      compliance.

PMID- 12510172
TI  - Ageing and wound healing.
AB  - Cutaneous wound healing is a complex process encompassing a number of overlapping
      events including leukocyte recruitment, matrix deposition, epithelialization, and
      ultimately resolution of inflammation with the formation of a mature scar.
      Morbidity associated with age-related delayed wound healing imposes an enormous
      social and financial burden; unless improved wound care strategies are developed
      the projected relative and absolute increase in the elderly population will
      further exacerbate this problem. In recent years insight has been gained into the
      impact of ageing on cellular and tissue responses, resulting from impaired
      cytokine signal transduction, unchecked inflammation, an altered balance of
      protein synthesis and degradation, and subsequent downstream effects on the rate
      and quality of the wound healing response. Further understanding of the complex
      interaction between the ageing cell and its microenvironment is essential in
      order to develop focussed therapeutic strategies to improve healing in the
      elderly.

PMID- 12510173
TI  - Dark neurons in the ageing cerebellum: their mode of formation and effect of
      Maharishi Amrit Kalash.
AB  - Dark neurons are considered a manifestation of neuronal injury and although they
      cover various grades of damage their mode of formation is not yet clear. Age
      dependent alterations in a dark purkinje neuronal population of guinea pigs (10
      months and 32 months old) and rats (3 months, 6 months, 12 months, 15 months and
      28 months) were studied. Light microscopical and electron microscopical
      observations revealed a significant increase (P < 0.05) in the number of dark
      purkinje neurons with age in both the guinea pigs and rats. Extraction of lipids
      from the cerebellum sections before processing for histochemical reaction
      resulted in a reduction of the dark neuronal population. In an other set of
      experiments, significant age-dependent increase in the cathepsin-D activity and
      lipid peroxidation was documented in the guinea pig cerebellum. Treatment of
      guinea pigs with Maharishi Amrit Kalash (MAK) (500 mg/kg body wt/day, for two
      months) significantly inhibited (P < 0.05) the activity of cathepsin-D and lipid
      peroxidation, and decreased the number of dark neurons. These findings suggest
      that the number of dark neurons increases with age and MAK prevents the
      conversion of light to dark purkinje neurons due to its inhibitory effects on
      cathepsin-D activity and antioxidant properties. We suggest that the
      conformational changes in the normal protein structure due to higher proteolytic
      activity and peroxidation of lipid in the aging cerebellum endangers a redundant
      capability for various staining agents and the Osimic acid molecules to react
      with proteins, lipids and other molecules, leading to an intensified cyto- and
      karyoplasms electron density.

PMID- 12510174
TI  - Lack of hypergravity-associated longevity extension in Drosophila melanogaster
      flies overexpressing hsp70.
AB  - Previous studies have shown that Drosophila melanogaster males live longer if
      exposed to hypergravity at young age. Similarly, thermotolerance and climbing
      activity in old age are enhanced and it has been hypothesized that the 70 kDa
      inducible heat-shock protein (hsp70) may play a role in some of these effects. In
      this article, longevity, thermotolerance and climbing activity were studied in
      transgenic flies (OE+ strain) overexpressing hsp70 and in control flies harboring
      the transfection vector at the same chromosomal location but no extra-copies of
      the hsp70 gene (OE- strain). No positive effect from exposure to hypergravity at
      a young age was observed for longevity and climbing activity. Thermotolerance was
      increased by hypergravity but to the same extent in OE+ and OE- strains. Since no
      positive effect from hypergravity exposure or similar effects were observed in
      the two strains, it may be concluded that overexpression of hsp70 does not
      provide an advantage to flies subjected to a mild stress and that it may not be
      of any help during aging.

PMID- 12510175
TI  - Telomerase positive human diploid fibroblasts are resistant to replicative
      senescence but not premature senescence induced by chemical reagents.
AB  - Human diploid fibroblasts in tissue culture undergo replicative senescence after
      a finite number of divisions that is characterized by a permanent loss of their
      dividing potential. However, senescence-like phenotypes, including growth
      cessation, morphological changes, and appearance of senescence-associated beta
      galactosidae (SA-gal) activity, can be induced by treating early passage cells
      with C(6)-ceramide, H(2)O(2), LY294002, or trichostatin A. While there is
      convincing evidence that telomere shortening is causally related to replicative
      senescence, the role of telomere shortening in the chemical-induced premature
      senescence is unclear. Here we employed a normal human BJ cell strain and its
      telomerase-transfected counterpart, termed BJ-T cells, to examine whether active
      telomerase in BJ-T can block or delay the premature senescence induced by various
      chemicals and, if not, whether telomere shortening still occurs. We found that,
      although all four chemicals tested could induce growth arrest, and in some cases
      SA-gal activity, in both BJ and BJ-T cells, only H(2)O(2) clearly caused an
      irreversible loss of dividing potential. H(2)O(2) treatment did not inhibit the
      cellular telomerase activity, nor did it cause any appreciable telomere
      shortening in BJ-T cells. These results suggest that oxidative stress and other
      chemical reagents can target at sites unrelated to the telomere-associated
      clocking mechanism. Alternatively these chemicals may bypass the telomere length
      maintenance machinery and target at its downstream sites.

PMID- 12510176
TI  - A mathematical model that accounts for the effects of caloric restriction on body
      weight and longevity.
AB  - Several aspects of energy dynamics, such as energy expenditure and caloric
      intake, are known to affect the aging process. In this article we therefore model
      the aging process within a mathematical framework describing the energy dynamics
      of an organism. The resulting model comprises food intake, body growth and
      survival. The equation for the mortality rate accounts for food consumption and
      is suited to describe caloric restriction data. For non-growing animals, the
      expression for the mortality rate reduces to the well-known Gompertz equation. We
      successfully applied our model to growth and survival data on mice exposed to
      different food levels.

PMID- 12510177
TI  - Stereologic study of the sinoatrial node of rats -- age related changes.
AB  - Changes in the sinoatrial node represent the major mechanism of sudden death in
      humans, and because of the sparse knowledge about the effects of aging on this
      structure, light microscopic and quantitative studies of the sinoatrial node were
      undertaken. Twenty-one hearts were studied, seven rat hearts from each of the
      following age groups: three months of age, twelve months of age and eighteen
      months of age. In the stereologic study, the following parameters were studied:
      Vv([nc]) and Vv([interstitium]) % (the volume densities of the nodal cell and
      interstitium, determined by the point-counting method), and Nv([nc]) (1/mm(3))
      (the numerical density of the nodal cell, determined by the disector method). The
      mean volume of the nodal cell (V([nc])) (microm(3)) was also determined. The
      comparisons showed that in the oldest animals, the volume density of the nodal
      cells decreased, while the volume density of the interstitium increased. Although
      numerical density of the nodal cell per volume of sinus node decreased, the nodal
      cells displayed increased mean volume with age. In conclusion, the aging process
      implies changes in the cell and fiber content of the sinoatrial node.

PMID- 12510178
TI  - Upper limb motor function in hemiparesis: concurrent validity of the Arm Motor
      Ability test.
AB  - OBJECTIVE: To evaluate the concurrent validity of the Arm Motor Ability Test
      (AMAT) using the Fugl-Meyer Assessment (FMA) as the criterion measure of
      poststroke upper limb motor impairment. DESIGN: Upper limb motor impairment and
      arm ability of 30 chronic stroke survivors were assessed with the FMA and AMAT,
      respectively. Spearman's correlation coefficients were generated relating the
      components of FMA and AMAT. Scatterplots were generated to provide qualitative
      assessments of the relationship between FMA and AMAT. Bar graphs of FMA and AMAT
      normalized to their maximum scores were generated to compare the levels of motor
      status measured by each instrument. RESULTS: All components of AMAT correlated
      highly with FMA total (r = 0.92-0.94; P < 0.001). AMAT functional ability and
      AMAT quality of movement were linearly related with FMA total. However, AMAT time
      of performance exhibited significant ceiling and floor effects with respect to
      FMA. Normalized AMAT scores were generally lower than normalized FMA scores (P <
      0.001), with the greatest difference in scores observed in subjects with more
      severe motor impairments. CONCLUSION: This study demonstrates a high degree of
      concurrent criterion validity of the AMAT. However, AMAT tends to underestimate
      the arm motor status of those with more severe motor impairments.

PMID- 12510179
TI  - Why do older adults decide they are having difficulty with a task?
AB  - OBJECTIVE: Previous studies have identified risk factors for decline in physical
      function, but they have not examined specific reasons older adults report
      difficulty with mobility tasks. DESIGN: Community-dwelling people ( n = 160) aged
      59 yr and older in an observational cohort study were questioned to determine the
      most common cited reasons for self-reported difficulty in task performance.
      RESULTS: Mobility tasks were most often reported to be difficult (66%). The
      reasons cited for difficulty in low exercise tolerance tasks were task
      modification by method (33%) and rate (33%). For high exercise tolerance tasks,
      reasons cited included having to modify the rate of performing the task (20%) or
      the method (13%). Among those who reported difficulty with low exercise tolerance
      mobility tasks, >80% reported modification (odds ratio, 46.4 [95% confidence
      limits: 9.75, 220.51]) and 32% also report frequency change (odds ratio, 5.9 [95%
      confidence limits: 2.72, 12.85]) as the reason for perceiving difficulty. For
      those who reported difficulty performing high exercise tolerance-demanding tasks,
      >90% reported modification (odds ratio, 5.5 [95% confidence limits: 2.05, 14.88])
      and 61% also report frequency changes (odds ratio, 3.9 [95% confidence limits:
      1.93, 8.04]). CONCLUSION: The findings suggest that people are able to cite
      specific reasons for difficulty with mobility task performance, most commonly
      related to task modification.

PMID- 12510180
TI  - Functional magnetic resonance image finding of cortical activation by
      neuromuscular electrical stimulation on wrist extensor muscles.
AB  - OBJECTIVE: To investigate the effects that neuromuscular electrical stimulation
      on the wrist extensor muscles have on the cerebral cortex. DESIGN: A functional
      magnetic resonance imaging study was performed on eight normal volunteers. The
      activation task was the maximum wrist extension by neuromuscular electrical
      stimulation, applied through a two-channel electrical stimulator. Monophasic
      square-wave pulses were used. The activation maps were generated by the threshold
      test maps. The level of primary motor cortex and primary sensory cortex
      activations was estimated. RESULTS: Among the eight subjects, seven showed
      significant activation on contralateral primary sensorimotor cortex by
      neuromuscular electrical stimulation on the wrist extensor muscles. In these
      seven subjects, additional bilateral or contralateral supplementary motor area
      activations were also observed. The number of activated pixels on the primary
      sensory cortex was slightly greater than that on the primary motor cortex.
      CONCLUSION: Neuromuscular electrical stimulation, when applied to the peripheral
      muscles, seems to have a direct effect on the cerebral cortex.

PMID- 12510181
TI  - Clinical trial of acupuncture for patients with spinal cord injuries.
AB  - OBJECTIVE: To examine whether electrical acupuncture therapy through adhesive
      surface electrodes and concomitant auricular acupuncture therapy could improve
      the neurologic or functional recovery in acute traumatic spinal cord injury
      patients. DESIGN: A total of 100 acute traumatic spinal cord injury patients with
      American Spinal Injury Association (ASIA) impairment grading of A and B were
      recruited into this study. They were randomly divided into the acupuncture and
      control groups. In the acupuncture group, electrical acupuncture therapy via the
      adhesive surface electrodes were applied to the bilateral Hou Hsi (SI3) and Shen
      Mo (B62) acupoints. In auricular acupuncture, four acupoints related to the
      spinal cord were selected for stimulation at the antihelix, helix, and lower
      portion of the ear-back areas. Acupuncture therapy was initiated early in the
      emergency room setting or soon after spinal surgical intervention. Rehabilitation
      therapy was also provided to the patients during acupuncture therapy. In the
      control group, only rehabilitation therapy was provided to the patients.
      Neurologic and functional scores were assessed during the time of admission,
      hospital discharge, and 1-yr postinjury follow-up. RESULTS: There were
      significant improvements in neurologic (sensory and motor), functional, and FIM
      scores in the acupuncture group compared with the initial admission period when
      assessed during the time of hospital discharge and the 1-yr postinjury follow-up.
      A greater percentage of patients in the acupuncture group recovered to a higher
      ASIA impairment grading. CONCLUSION: The use of concomitant auricular and
      electrical acupuncture therapies, when implemented early in acute spinal cord
      injury, can contribute to significant neurologic and functional recoveries.

PMID- 12510182
TI  - Serologic examinations of hepatitis, cytomegalovirus, and rubella in patients
      with Bell's palsy.
AB  - OBJECTIVE: The aim of this retrospective case review was to investigate serologic
      evidence of cytomegalovirus, rubella virus, and hepatitis A, B, and C viruses in
      patients with Bell's palsy. DESIGN: A total of 24 patients with idiopathic facial
      paralysis, without a history of trauma, any evidence of a tumor on high
      resolution computed tomographic imaging, or any otologic disease, and 33 healthy
      individuals as a control group were included in this study. Facial paralysis of
      the patient was evaluated with the House-Brackmann grading scale. Specific
      immunoglobulin G and M titers were determined for cytomegalovirus, rubella,
      hepatitis A, hepatitis B, and hepatitis C by enzyme-linked immunosorbent assay.
      RESULTS: Serologic positivity for hepatitis B was found in 15 of 21 Bell's palsy
      patients, compared with 32.1% in the control group. The difference was
      statistically significant. There was no difference in the prevalence of serologic
      positivity for cytomegalovirus, hepatitis A, and rubella between the patient and
      control groups. In one Bell's palsy patient, serologic evidence of recent
      cytomegalovirus infection was indicated by changes in antibody titers between
      samples taken on presentation and on the 16th day. There was no serologic
      evidence of hepatitis C in either Bell's palsy patients or the control group.
      CONCLUSION: There seems to be an association between hepatitis B and idiopathic
      facial paralysis. In addition, cytomegalovirus might contribute to the
      development of Bell's palsy in some ceases with Bell's palsy. Further studies are
      required to confirm these data.

PMID- 12510183
TI  - Brief assessment of motor function: reliability and concurrent validity of the
      Gross Motor Scale.
AB  - OBJECTIVE: The Brief Assessment of Motor Function (BAMF) is a series of 10-point
      ordinal scales developed for rapid description of gross motor, fine motor, and
      oral motor performance. We examined interrater and intrarater reliability and
      concurrent validity of the BAMF Gross Motor Scale. DESIGN: This validation study
      included 48 children (age, 5 mo to 17 yr) with a wide range of gross motor
      capability. Ten children with varied diagnoses participated in the reliability
      study. For concurrent validity, the BAMF performance of 38 children with
      osteogenesis imperfecta was compared with scores on the Peabody Developmental
      Motor Scales, laboratory gait analysis, and manual muscle testing. RESULTS:
      Reliability values for intraclass correlations were 0.996 (interrater) and 1.00
      (intrarater). Significant relationships were identified between the BAMF and gait
      speed ( r = 0.68, P < 0.0001), stride length (r = 0.71, P < 0.0001), duration of
      double-limb support ( r = -0.40, P < 0.03), number of weak muscles (r = -0.74, P<
      0.0001), and the Peabody Developmental Motor Scales (r = 0.95, P < 0.0001).
      Number of weak muscles was the strongest predictor of BAMF score R2 = 0.5080, F =
      24.77, P < 0.0001). CONCLUSIONS: The BAMF demonstrates good reliability for
      children with a range of diagnoses and acceptable concurrent validity with gross
      motor development, muscle strength, and formal gait assessment in children with
      osteogenesis imperfecta.

PMID- 12510184
TI  - Postural control during sit-to stand and gait in stroke patients.
AB  - OBJECTIVE: To investigate the relationship of sit-to-stand and gait performance
      in hemiplegic stroke patients. DESIGN: A total of 40 chronic stroke patients with
      hemiplegia and 22 age-matched healthy subjects were included in this study. Data
      of a motion analysis system and three force platforms were collected in a
      rehabilitation unit of a medical center. RESULTS: Laboratory sit-to-stand
      measurement and gait analysis were evaluated in both groups via three AMTI
      (Advanced Mechanical Technology Inc.) force platforms and a Vicon 370 system (six
      high-resolution cameras and one AMTI force plate), respectively. The sit-to-stand
      and gait parameters of hemiplegic patients were correlated significantly,
      especially in rising speed and the maximal vertical force of both legs during
      rising. CONCLUSIONS: Hemiplegic stroke patients, who could stand up within 4.5
      sec or who had a maximal vertical force difference of less than 30% of body
      weight between both legs, had better gait performance than the others did.

PMID- 12510185
TI  - Hemorrhagic transformation in stroke patients.
AB  - OBJECTIVE: To identify the predictors of hemorrhagic transformation in stroke
      patients and to evaluate the impact of hemorrhagic transformation on
      rehabilitation outcome. DESIGN: The records of 203 hemiplegic patients
      hospitalized for rehabilitation after the acute phase of stroke were
      retrospectively analyzed. In 121 cases, the first computed tomographic scan and a
      repeat scan were compared to determine whether hemorrhagic transformation
      occurred. Correlations between the occurrence of hemorrhagic transformation and
      use of anticoagulants, antiaggregants, and antiedema drugs were evaluated.
      Admission and discharge FIM trade mark and Adapted Patient Evaluation Conference
      System scores were noted, and functional gain was calculated from these. These
      data were also analyzed for associations with hemorrhagic transformation.
      RESULTS: Hemorrhagic transformation was detected in 39 of the 121 cases. There
      was no significant difference in functional outcome between patients who did and
      did not show hemorrhagic transformation. Although not statistically significant,
      the use of antiedema drugs was found to increase the risk of hemorrhagic
      transformation, whereas the use of anticoagulants and antiaggregants had no
      influence. CONCLUSIONS: Hemorrhagic transformation of an ischemic lesion does not
      affect rehabilitation outcome in stroke survivors. The study results favor the
      use of anticoagulants and antiaggregants in the acute phase unless these drugs
      are contraindicated by the patient's condition. Still, prospective trials are
      needed to make definite conclusions.

PMID- 12510186
TI  - Use of somatosensory-evoked potentials and cognitive event-related potentials in
      predicting outcomes of patients with severe traumatic brain injury.
AB  - OBJECTIVE: This study was performed to evaluate the usefulness of somatosensory
      evoked potentials (SEPs) and cognitive event-related potentials (ERPs) in
      predicting functional outcomes of severe traumatic brain injury patients. DESIGN:
      Prospective study of 22 patients with severe traumatic brain injury. Demographic
      information, Glasgow Coma Scale, and electrophysiologic measurements were
      recorded. Functional outcomes, as quantified by the Glasgow Outcome Scale
      Extended, were obtained. RESULTS: Bilateral absence of median nerve SEP was
      strongly predictive of the worst functional outcome. The specificity and positive
      predictive value of absent SEP for predicting death or persistent vegetative
      state at 6 mo after traumatic brain injury were as high as 100%. If the
      definition of unfavorable outcome was expanded to include Glasgow Outcome Scale
      Extended 1-4, absence of ERP was equivalent to the absence of SEP in specificity
      and positive predictive value. On the other hand, normal ERPs showed higher
      sensitivity and negative predictive value for prognosticating the best outcomes
      compared with normal SEPs. If the definition of favorable outcome was expanded to
      include Glasgow Outcome Scale-Extended 5-8, ERP was still superior to SEP for
      prognosticating good outcome. Interestingly, the highest sensitivity and negative
      predictive value for favorable outcomes were associated with the presence of any
      discernible waveform. CONCLUSIONS: Although median nerve SEP continues to make
      reliable prediction of ominous outcome in severe traumatic brain injury, the
      addition of the speech-evoked ERPs may be helpful in predicting favorable
      outcomes. The strength of the latter test seems to complement the weakness of the
      former.

PMID- 12510187
TI  - Rehabilitation hospital staff knowledge and attitudes regarding pain.
AB  - No published studies exist that document pain-related knowledge, attitudes, or
      educational needs of clinical staff in a rehabilitation hospital; the purpose of
      this study was to obtain such information to aid in the development of an
      institutional pain care improvement project. A survey regarding knowledge and
      attitudes about pain and perceived areas of educational need was administered to
      all staff with inpatient care responsibilities. Results show that rehabilitation
      hospital staff hold generally progressive attitudes toward the treatment of pain
      but with a substantial degree of ambivalence about the use of opioids in the
      treatment of pain. Staff rate their own lack of education about pain management
      as one of the chief barriers to effective pain management, and a large percentage
      report feeling uncomfortable with various technical aspects of pain care. We
      discuss the implications of this survey for understanding and improving pain care
      in rehabilitation settings.

PMID- 12510188
TI  - "Young" lumbar spinal stenotic: review of 268 patients younger than 51 years.
AB  - Historically, most patients with the lumbar spinal stenosis have been older than
      66 yr when initially diagnosed; however, with a growing awareness of this entity,
      it is increasingly being identified at an earlier age. A 5-yr retrospective
      review of hospital records was initiated to determine the frequency of lumbar
      spinal stenosis in a population of patients of <51 yr of age. Of 2751 patients
      admitted with this diagnosis, 268 (9.8%) were <51 yr of age.

PMID- 12510189
TI  - Current implications of drug resistance in spinal cord injury.
AB  - A 54-yr-old man with C6 quadriplegia and a neurogenic bowel and bladder was
      evaluated for clearance of a urinary tract infection after treatment for
      organisms susceptible to the antibiotics used, and an organism resistant to all
      antibiotics on the panel grew on the initial follow-up urine culture. Multidrug
      resistant organisms present increasing challenges and risks in the management of
      the neurogenic bladder in patients with spinal cord injury. In an effort to
      control and reduce the impact and risk associated with these organisms,
      management methods of the neurogenic bladder and infection control policies
      should be adjusted according to guidelines from the Centers for Disease Control
      and related research; such policies could include surveillance for multidrug
      resistant organisms and isolation of patients who test positive for these
      organisms.

PMID- 12510190
TI  - Modified constraint-induced therapy and botulinum toxin A: a promising
      combination.
AB  - Modified constraint-induced therapy and chemodenervation with botulinum toxin A
      are each efficacious in managing stroke-induced motor disorders; however, the
      application of these two promising modalities in combination is yet to be
      examined. This case study describes a 44-yr-old man who experienced a right
      middle cerebral artery infarct 14 mo before participating in modified constraint
      induced therapy. After modified constraint-induced therapy completion, the
      patient exhibited substantial improvement in affected upper limb use and function
      but retained difficulty with finger extension secondary to hypertonicity and
      spasticity in the forearm flexor muscles. Selective chemodenervation of these
      muscles with botulinum toxin A greatly improved the patient's self-reported hand
      function and his scores using objective measures. The authors of this paper
      present this case to raise the idea of increasing treatment efficacy by combining
      these two modalities.

PMID- 12510191
TI  - Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitochondria and inhibits
      apoptosis.
AB  - The mitochondrial localization of the membrane proteins Bcl-2 and Bcl-x(L) is
      essential for their anti-apoptotic function. Here we show that mitochondrial
      FK506-binding protein 38 (FKBP38), unlike FKBP12, binds to and inhibits
      calcineurin in the absence of the immunosuppressant FK506, suggesting that FKBP38
      is an inherent inhibitor of this phosphatase. FKBP38 is associated with Bcl-2 and
      Bcl-x(L) in immunoprecipitation assays and colocalizes with these proteins in
      mitochondria; in addition, the expression of FKBP38 mutant proteins induces a
      marked redistribution of Bcl-2 and Bcl-x(L). Overexpression of FKBP38 blocks
      apoptosis, whereas functional inhibition of this protein by a dominant-negative
      mutant or by RNA interference promotes apoptosis. Thus, FKBP38 might function to
      inhibit apoptosis by anchoring Bcl-2 and Bcl-x(L) to mitochondria.

PMID- 12510192
TI  - Signalling and crosstalk of Rho GTPases in mediating axon guidance.
AB  - Axon extension during development of the nervous system is guided by many
      factors, but the signalling mechanisms responsible for triggering this extension
      remain mostly unknown. Here we have examined the role of Rho family small
      guanosine triphosphatases (GTPases) in mediating axon guidance by diffusible
      factors. Expression of either dominant-negative or constitutively active Cdc42 in
      cultured Xenopus laevis spinal neurons, at a concentration that does not
      substantially affect filopodial formation and neurite extension, abolishes the
      chemoattractive growth cone turning induced by a gradient of brain-derived
      neurotrophic factor that can activate Cdc42 and Rac in cultured neurons.
      Chemorepulsion induced by a gradient of lysophosphatidic acid is also abolished
      by the expression of dominant-negative RhoA. We also show that an asymmetry in
      Rho kinase or filopodial initiation across the growth cone is sufficient to
      trigger the turning response and that there is a crosstalk between the Cdc42 and
      RhoA pathways through their converging actions on the myosin activity essential
      for growth cone chemorepulsion.

PMID- 12510193
TI  - Interactions between the crumbs, lethal giant larvae and bazooka pathways in
      epithelial polarization.
AB  - Several protein complexes that are involved in epithelial apicobasal polarity
      have been identified. However, the mechanism by which these complexes interact to
      form an integrated polarized cell morphology remains unclear. Crumbs (Crb) and
      Lethal giant larvae (Lgl) are components of distinct complexes that regulate
      epithelial polarization in Drosophila melanogaster, but may not interact directly
      as they localize to the apical and basolateral membrane, respectively.
      Nevertheless, a genetic screen identifies marked functional interactions between
      crb and lgl. These interactions extend to other genes within the crb (stardust,
      sdt) and lgl (discs large, dlg; scribble, scrib) pathways. Our findings suggest
      that the crb and lgl pathways function competitively to define apical and
      basolateral surfaces. They also suggest that in the absence of lgl pathway
      activity, the crb pathway is not required to maintain epithelial polarity.
      Moreover, we show that crb and lgl cooperate in zonula adherens formation early
      in development. At later stages, epithelial cells in these mutants acquire normal
      polarity, indicating the presence of compensatory mechanisms. We find that
      bazooka (baz) functions redundantly with crb/sdt to support apical polarity at
      mid- to late-embryogenesis. Despite regaining cell polarity, however, epithelial
      cells in crb and lgl pathway mutants fail to re-establish normal overall tissue
      architecture, indicating that the timely acquisition of polarized cell structure
      is essential for normal tissue organization.

PMID- 12510194
TI  - Integrated activity of PDZ protein complexes regulates epithelial polarity.
AB  - Polarized cells contain numerous membrane domains, but it is unclear how the
      formation of these domains is coordinated to create a single integrated cell
      architecture. Genetic screens of Drosophila melanogaster embryos have identified
      three complexes, each containing one of the PDZ domain proteins--Stardust (Sdt),
      Bazooka (Baz) and Scribble (Scrib)--that control epithelial polarity and
      formation of zonula adherens. We find that these complexes can be ordered into a
      single regulatory hierarchy that is initiated by cell adhesion-dependent
      recruitment of the Baz complex to the zonula adherens. The Scrib complex
      represses apical identity along basolateral surfaces by antagonizing Baz
      initiated apical polarity. The Sdt-containing Crb complex is recruited apically
      by the Baz complex to counter antagonistic Scrib activity. Thus, a finely tuned
      balance between Scrib and Crb complex activity sets the limits of the apical and
      basolateral membrane domains and positions cell junctions. Our data suggest a
      model in which the maturation of epithelial cell polarity is driven by
      integration of the sequential activities of PDZ-based protein complexes.

PMID- 12510195
TI  - Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor
      protein pVHL.
AB  - Von Hippel-Lindau (VHL) tumour suppressor gene inactivation is linked to the
      development of haemangioblastomas in the central nervous system and retina, often
      in association with other tumours, such as clear-cell carcinomas of the kidney
      and phaeochromocytomas. Here we show that the VHL protein (pVHL) is a microtubule
      associated protein that can protect microtubules from depolymerization in vivo.
      Both the microtubule binding and stabilization functions of pVHL depend on amino
      acids 95-123 of pVHL, a mutational 'hot-spot' in VHL disease. From analysis of
      naturally occurring pVHL mutants, it seems that only point mutations such as
      pVHL(Y98H) and pVHL(Y112H) (that predispose to haemangioblastoma and
      phaeochromocytoma, but not to renal cell carcinoma) disrupt pVHL's microtubule
      stabilizing function. Our data identify a role for pVHL in the regulation of
      microtubule dynamics and potentially provide a link between this function of pVHL
      and the pathogenesis of haemangioblastoma and phaeochromocytoma in the context of
      VHL disease.

PMID- 12510196
TI  - Epsilon-tubulin is required for centriole duplication and microtubule
      organization.
AB  - Centrosomes nucleate microtubules and serve as poles of the mitotic spindle.
      Centrioles are a core component of centrosomes and duplicate once per cell cycle.
      We previously identified epsilon-tubulin as a new member of the tubulin
      superfamily that localizes asymmetrically to the two centrosomes after
      duplication. We show that recruitment of epsilon-tubulin to the new centrosome
      can only occur after exit from S phase and that epsilon-tubulin is associated
      with the sub-distal appendages of mature centrioles. Xenopus laevis epsilon
      tubulin was cloned and shown to be similar to human epsilon-tubulin in both
      sequence and localization. Depletion of epsilon-tubulin from Xenopus egg extracts
      blocks centriole duplication in S phase and formation of organized centrosome
      independent microtubule asters in M phase. We conclude that epsilon-tubulin is a
      component of the sub-distal appendages of the centriole, explaining its
      asymmetric localization to old and new centrosomes, and that epsilon-tubulin is
      required for centriole duplication and organization of the pericentriolar
      material.

PMID- 12510197
TI  - The Drosophila HOAP protein is required for telomere capping.
AB  - HOAP (HP1/ORC-associated protein) has recently been isolated from Drosophila
      melanogaster embryos as part of a cytoplasmic complex that contains
      heterochromatin protein 1 (HP1) and the origin recognition complex subunit 2
      (ORC2). Here, we show that caravaggio, a mutation in the HOAP-encoding gene,
      causes extensive telomere-telomere fusions in larval brain cells, indicating that
      HOAP is required for telomere capping. Our analyses indicate that HOAP is
      specifically enriched at mitotic chromosome telomeres, and strongly suggest that
      HP1 and HOAP form a telomere-capping complex that does not contain ORC2.

PMID- 12510198
TI  - Critical appraisal of effects of estrogen replacement therapy on symptoms of
      depressed mood.
AB  - That estrogen plays a role in the regulation of mood has been postulated since
      extracts of animal ovarian tissue were administered to oophorectomized women at
      the end of the last century to alleviate psychological symptoms thought to be
      related to the removal of the ovaries. The occurrence of depressive symptoms in
      the perimenopause is associated with a variety of factors. A previous history of
      either depression and/or premenstrual syndrome as well as cognitive factors
      explain most of the variance. There are no consistent findings of a correlation
      between any serum hormone level and severity or presence of mood symptoms.
      Neurobiological studies show, with regard to an antidepressant effect, promising
      effects of estradiol on serotonergic, noradrenergic, cholinergic, dopaminergic
      and GABAergic functions. Progestogens seem to oppose some of these effects. The
      role of adrenergic hormones and DHEA(S) is less clear. Most clinical trials
      showed a modest effect on symptoms of depression. However, the predominantly poor
      methodological quality does not allow generalisation and recommendations. A
      "tonic" effect on well-being in non- or mild depressed women should not be
      regarded as true antidepressant effect. Results yielded in studies of surgically
      menopausal women may not be applicable to women with natural menopause. There is
      a great potential for exploring various types, doses, and routes of
      administration of both antidepressants and sex hormones. With regard to the
      domino theory, future studies should also focus on the mediation of treatment
      effects through alleviation of vasomotor symptoms or sleep quality.

PMID- 12510199
TI  - Care in a mother-baby psychiatric unit: analysis of separation at discharge.
AB  - Joint psychiatric admission to a Mother-Baby Unit (MBU) enables a mother to
      obtain care for psychiatric disorders and simultaneously receive support in
      developing her identity as a mother. This care is meant to prevent attachment
      disorders and mother-baby separation. Outcome at discharge, however, may differ
      according to the mother's admission diagnosis. Demographic data, clinical
      features of parent and child, and clinical outcome of 92 consecutive admissions
      of mothers and their children to a MBU in Marseille were collected over a period
      of eight years (1991-1998). Separations occurred in 23% of the joint admissions.
      Women with acute postpartum psychoses and major depressive disorders had better
      outcomes than those with chronic psychoses: at discharge, the latter were more
      often separated from their children. In those cases, however, MBU admission
      provided time to arrange the best placement for the child. Outcome was less
      predictable for non-psychotic personality disorders and depended not only on the
      mother's disease but also on her family and social context.

PMID- 12510200
TI  - Sexual dysfunction in women: population based epidemiological study.
AB  - Sexual dysfunction is defined as a disturbance of the processes that characterise
      the sexual response cycle or as pain associated with sexual intercourse. The
      objective of this epidemiological study, conducted in a representative sample of
      the population of women aged 20 and older in Casablanca, Morocco, is to determine
      the prevalence of sexual dysfunction in women. Criteria of sexual dysfunction
      followed classification by DSM-IV. The mean age of the sample (n = 728) was 36.76
      +/- 12.67 years; 29% had no education, 78% pursued no professional activity; and
      58% were married. The main results were that 26.6% had sexual dysfunction always
      or often during the 6 months before the study. The most common finding was
      hypoactive sexual desire disorder, and age, financial dependency, number of
      children, and sexual harassment were positively associated. The prevalence of
      remaining disorders resembled that found in the literature. Even though these
      women were aware about their disorder and its negative impact on their lives,
      only 17% of them asked for help.

PMID- 12510201
TI  - Postpartum depression: prevalence and determinants in Lebanon.
AB  - This study assesses the prevalence and determinants of postpartum depression
      (PPD). 396 women delivering in Beirut and a rural area (Beka'a Valley) were
      interviewed 24 hours and 3-5 months after delivery. During the latter visit, they
      were screened using the Edinburgh postnatal depression scale. The overall
      prevalence of PPD was 21% but was significantly lower in Beirut than the Beka'a
      Valley (16% vs. 26%). Lack of social support and prenatal depression were
      significantly associated with PPD in both areas, whereas stressful life events,
      lifetime depression, vaginal delivery, little education, unemployment, and
      chronic health problems were significantly related to PPD in one of the areas.
      Prenatal depression and more than one chronic health problem increased
      significantly the risk of PPD. Caesarean section decreased the risk of PPD,
      particularly in Beirut but also in the Beka'a Valley. Caregivers should use pre-
      and postnatal assessments to identify and address women at risk of PPD.

PMID- 12510202
TI  - Possible influence of selection bias on gender differences in the risk of
      Alzheimer's disease.
AB  - For the observation of a higher risk of Alzheimer's disease (AD) in women, causes
      like a general longer life expectancy of women, a longer lifespan of women with
      AD, a later age at onset and a lower level of education compared with men have
      been discussed. However, methodological artefacts could also contribute to the
      observed gender difference. Data from a comprehensive family study was re
      evaluated, in which a gender difference in the risk of AD had been observed.
      Available relatives had been directly interviewed, information on unavailable
      ones was provided by thirds. A differential, gender specific participation led to
      the under-representation of older and demented men, creating a selection bias,
      that may be the cause for the observed gender difference in the risk of AD. Study
      methods must be taken into account when interpreting information on gender
      differences in the risk of AD.

PMID- 12510203
TI  - Screening women for postpartum depression at well baby visits: resistance
      encountered and recommendations.
AB  - OBJECTIVE: Postpartum major depression afflicts 10-15% of childbearing women and
      can have serious consequences. Unrecognized and therefore untreated episodes of
      postpartum major depression can predispose women to future depressive episodes,
      especially those related to other reproductive events. In the United States,
      women typically have one visit at six weeks postpartum with their obstetrician
      which is focused on physical recovery from delivery. Pediatricians typically see
      new mothers 4-6 times per year at well baby visits. Therefore, our objective is
      to test the utility of screening women for postpartum depression at each well
      baby visit over the course of the first postpartum year as compared with controls
      derived from clinical practice and chart review. METHOD: Subjects for this
      prospective study were recruited at their first well baby visit at the UCSD
      Primary Care Pediatric Clinic and interviewed by telephone. Subjects then were
      asked to complete the Edinburgh Postnatal Depression Scale (EPDS) and the Beck
      Depression Inventory (BDI) at intervals consistent with the timing of well baby
      visits. If scores on the EPDS or the BDI exceeded the thresholds (EPDS >or= 12
      and BDI >or= 10) then subjects were assessed further with the Structured Clinical
      Interview for the Diagnostic and Statistical Manual of Mental Disorder, Fourth
      Edition (SCID-DSM IV). If diagnosed with postpartum major depression, subjects
      were referred for appropriate treatment. RESULTS: Out of 160 study packets
      distributed, only 7 women volunteered for the study, despite endorsement and
      presentation of the study by their pediatricians. Of those participants, five
      scored above threshold values at some point in the interval studied. DISCUSSION:
      The difficulty in recruitment in this study highlights some of the problems
      encountered in clinical practice in terms of identifying and referring women with
      postpartum mental illnesses. We recommend further study be focused on how to
      attract potentially affected women while simultaneously addressing their fears of
      stigma. Since resistance also was encountered in other physicians, we recommend
      that educational efforts be aimed at increasing knowledge and awareness of
      postpartum mental illnesses in both the lay and professional spheres.

PMID- 12510204
TI  - Fertility and number of children in patients with Alzheimer's disease.
AB  - Oestrogen therapy has been suggested to have protective effects against
      Alzheimer's disease. The effects of natural exposure to oestrogen in cognitive
      disorders have rarely been studied. Assuming that nulliparous women have a higher
      exposure to natural oestrogen, it could be hypothesised that these women might
      have a lower risk of Alzheimer's disease than women who have had children. The
      fertility and number of children in 106 women with a diagnosis of Alzheimer's
      disease was examined and compared with that of 189 female subjects from two
      control groups with subjects without dementia. As additional control, the same
      comparisons were carried out for 40 male patients with Alzheimer's disease and
      105 male control subjects. In female subjects, having had children was found to
      be associated with a diagnosis of Alzheimer's disease. This was not the case in
      male subjects. The number of children did not seem to affect the risk of
      Alzheimer's disease, neither in female nor in male subjects. Natural exposure to
      oestrogen seems to reduce the risk of Alzheimer's disease in women.

PMID- 12510205
TI  - Affective disorders in the aftermath of miscarriage: a comprehensive review.
AB  - We review the research literature regarding affective symptomatology and
      disorders following miscarriage, with an emphasis on controlled studies and those
      that have been published since the last review article in 1996. The current
      review draws a sharp distinction between controlled and uncontrolled designs and
      clarifies the proper inferences that may be drawn from each, as only with an
      appropriate comparison group can it be determined whether the affective reactions
      following miscarriage are a specific consequence of the reproductive loss or of
      other life events common in women of reproductive age. In addition to providing
      an update of the literature on depression in the aftermath of miscarriage and
      associated risk factors, we also discuss reproductive loss in the context of
      attachment theory and grief, and present information on topics that were not
      covered extensively (or at all) by prior reviews, such as issues related to a
      pregnancy subsequent to miscarriage and the impact of miscarriage on the partners
      of miscarrying women. In the final section, treatment options relevant to
      miscarriage are presented.

PMID- 12510206
TI  - Hormonal and genetic influences on behavioral dispositions related to
      reproduction.
AB  - Success in elucidating neural and genetic mechanisms for a female-typical
      sociosexual behavior have encouraged new work on mechanisms for the underlying
      concepts, motivation and arousal. Evidence for global arousal is adduced, and
      brainstem pathways contributing to global arousal are under investigation.

PMID- 12510207
TI  - Sex-role orientation, marital status and mental health in working women.
AB  - The objectives of this study were to make a men-women comparison as to the
      effects of job stress and sex-role orientation on mental health and to determine
      if marital status modifies effects of job stress and sex-role orientation on
      mental health in women. Subjects were 644 men and 301 women who were working at
      two private companies and one national agency. Job contents, sex-role orientation
      and mental health were measured by the Job Content Questionnaire, the Bem Sex
      Role Inventory and the 30-item General Health Questionnaire, respectively. High
      job demands and femininity in men, masculinity in women predicted poor mental
      health. The best predictor of poor mental health was consciousness of being a
      woman in unmarried women, and stress outside the job in married women.

PMID- 12510208
TI  - Breaking bad news in obstetrics and gynecology: educational conference for
      resident physicians.
AB  - To educate the Obstetrics and Gynecology residents about how to conduct
      conversations about poor prognoses, a panel discussion was scheduled, with
      patient-educators teaching about their experiences receiving bad news. The
      resident physicians reported that this conference format was an effective method
      for teaching this content. The patient-educators appreciated assisting the
      physicians, were comfortable in the conference setting, and reported a
      willingness to return for conferences in the future.

PMID- 12510210
TI  - Oestrogens and schizophrenia--introduction.

PMID- 12510211
TI  - Antipsychotic drugs, menstrual regularity and osteoporosis risk.
AB  - This report summarizes the preliminary results of a study in progress, a survey
      of 200 women with schizophrenia in long-term treatment with antipsychotic
      medication. In the context of providing clinical service to these women (Seeman,
      1997; Seeman and Cohen, 1998), we have begun to investigate the possibility of an
      association among related factors: type of antipsychotic drug use, the presence
      of amenorrhea, hyperprolactinemia and risk for osteoporosis (Biller et al., 1992;
      Grinspoon et al., 1999; Halbreich and Palter, 1996; More et al., 2001; Peuskens,
      1997; Sowers et al., 1995).

PMID- 12510212
TI  - A clinical trial of adjunctive oestrogen treatment in women with schizophrenia.
AB  - A double-blind, 28-day, placebo-controlled study was conducted with three groups
      of women of child-bearing age (N = 12 in each group) who received standardised
      antipsychotic medication plus a) 50 microg transdermal estradiol or b) 100 microg
      transdermal estradiol or c) transdermal placebo. Preliminary analyses show that
      women receiving 100 microg of estradiol made greater improvements in the symptoms
      of schizophrenia than either the 50 microg estradiol or placebo groups. The
      addition of 100 microg adjunctive transdermal oestrogen significantly enhanced
      treatment responsivity of acute, severe psychotic symptoms in women with
      schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms
      via a multiplicity of possible actions (see accompanying articles in this issue)
      may prove clinically useful in the overall treatment of women with schizophrenia.

PMID- 12510213
TI  - Neuroprotective effects of estradiol-17beta: implications for psychiatric
      disorders.
AB  - Estradiol-17beta is the most potent female sex hormone. In addition to its role
      in the control of primary and secondary sexual characteristics, it also
      influences the development of the brain. Furthermore, estradiol-17beta possesses
      neuroprotective properties that are mediated via receptor action and also
      independently of receptors. Several processes that are regulated by estradiol
      17beta might influence the expression of Alzheimer's disease and schizophrenia.
      Differences between the sexes have been described in both disorders, and it has
      been suggested that these may be due to the action of oestrogens. Long-term
      oestrogen replacement has proved to be beneficial in the prevention and treatment
      of Alzheimer's disease and schizophrenia. The results, however, are
      controversial. Preliminary in vitro and in vivo findings, which are summarised in
      this review, encourage further studies with estradiol-17beta or its analogues as
      potential adjunctive interventions particularly in "negative syndrome"
      schizophrenia and in Alzheimer's disease.

PMID- 12510214
TI  - Oestrogen effects in schizophrenia and their potential therapeutic implications-
      review.
AB  - Increasing evidence from clinical as well as from epidemiological and basic
      research shows that oestrogens exert protective effects in schizophrenia. A brief
      overview of these protective effects will be provided, and potential therapeutic
      implications will be discussed. If these effects are confirmed, they could have
      important implications for prophylaxis and treatment. For instance, consideration
      would need to be given to oestrogen replacement in peri- and postmenopausal women
      with schizophrenia, adjunct oestrogen therapy in women with oestrogen deficiency
      syndromes, cycle-modulated neuroleptic therapy in women with frequent
      perimenstrual relapses, and/or emphasis on prolactin-sparing atypical
      neuroleptics in women with hypoestrogenism. Further research is urgently needed
      since there may be direct therapeutic benefits for women.

PMID- 12510215
TI  - Acute psychiatric admission and menstrual cycle phase in women with
      schizophrenia.
AB  - The clinical observation of a possible relation between the phases of the
      menstrual cycle and psychotic illness dates well back to the beginning of the
      nineteenth century. This relation is considered to provide further evidence for
      the protective effect of oestrogens in schizophrenic women and is summarised by
      the so-called oestrogen hypothesis. In addition, the hypoestrogenism hypothesis
      postulates a hypofunction of the gonads in women with schizophrenia with
      subsequent oestrogen deficiency syndrome. The aim of the present clinical study
      was to answer the question whether there is a perimenstrual increase in hospital
      admissions of women suffering from an exacerbation of schizophrenia. Two samples
      of premenopausal women with schizophrenia were investigated (sample 1: n = 115;
      sample 2: n = 170). In both samples there was a significant increase in
      admissions in the perimenstrual phase - three days before and three days after
      the first day of the menses (sample 1: P = 0.002, sample 2: P = 0.028, binomial
      test). 37.4% of the patients were admitted during the perimenstrual phase of the
      cycle in sample 1, 31.8% in sample 2. Regarding age, age at onset, and duration
      of illness, no difference was found between the group admitted to hospital during
      the perimenstrual phase versus the group admitted during the rest of the
      menstrual cycle in either of the samples. The results are discussed in relation
      to the possibly underlying physiological mechanisms.

PMID- 12510219
TI  - Burning issues in gastrointestinal endoscopy at the start of the new millennium
      [correction of millenium].

PMID- 12510220
TI  - Ulcers and gastritis.
AB  - This article reviews recently published literature regarding ulcers and
      gastritis. Although endoscopy is the most useful procedure for diagnosis in the
      upper gastrointestinal tract, complications do occur, and procedure-related costs
      are significant. The appropriate indication for endoscopy has recently been
      debated. Helicobacter pylori is known to be an important pathogen involved in
      gastric and duodenal inflammation. Peptic ulcer disease and severe gastric
      mucosal injury are caused by virulent strains, and many reports have focused on
      CagA. Follow-up studies on surveillance endoscopy in patients with peptic ulcer
      or gastritis report that patients with atrophic gastritis and intestinal
      metaplasia are at significantly higher risk for gastric cancer. H. pylori
      eradication sometimes causes gastroduodenal erosion and reflux esophagitis, and
      the mechanisms involved have been revealed. Proton-pump inhibitors are useful in
      the treatment of ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs),
      reflux esophagitis, and for preventing rebleeding after endoscopic hemostasis,
      but the effect of long-term acid suppression on the gastric mucosa is still a
      matter of debate. H. pylori infection and NSAID intake are both risk factors for
      peptic ulcer disease, and are important aspects in this field.

PMID- 12510221
TI  - Small-bowel endoscopy.
AB  - This review of the literature on endoscopy of the small bowel focuses on
      published reports, and does not include abstracts. The literature was reviewed
      for the period September 2001 to September 2002. MEDLINE was searched under the
      topics of "small-bowel endoscopy", "small bowel", "enteroscopy", "obscure
      bleeding", and "wireless endoscopy", and a hand search was also carried out of
      the major gastroenterology journals, along with a review of the tables of
      contents of all journals that could be identified as being related to
      gastroenterology or gastrointestinal endoscopy. Sonde small-bowel enteroscopy is
      no longer an option, and has been rightfully retired as an investigation tool for
      the small bowel. There is still a place for further evaluation of push
      enteroscopy, as evidenced by the 11 papers published since the last review of
      small-bowel endoscopy in 2002. In the field of intraoperative enteroscopy, only
      one series and a handful of case reports have appeared. By contrast, wireless
      capsule endoscopy of the small bowel has captured the imagination of
      gastroenterologists throughout the world. Up to 2003, there have not been many
      published papers concerning this new diagnostic modality, since patients with
      obscure gastrointestinal bleeding or suspected small-bowel disease are relatively
      scarce. Large numbers of abstracts concerning capsule endoscopy have been
      submitted for presentation at major gastroenterology and gastrointestinal
      endoscopy meetings over the past 2 years, and the enthusiasm for this new
      technique of small-bowel imaging has increased with reports of its successful
      application.

PMID- 12510222
TI  - Ulcers and nonvariceal bleeding.
AB  - Peptic ulcer remains the commonest and most significant cause of nonvariceal
      upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding is rising
      in elderly patients, particularly for duodenal ulcer. Patients presenting with
      upper gastrointestinal bleeding who have low Rockall scores are at low risk of
      rebleeding and death. These patients currently utilize considerable health-care
      resources, but could safely be managed at home. The Rockall score can be used to
      predict the risk of rebleeding and death following variceal bleeding, but for
      patients with ulcer bleeding, its ability to predict death is questioned. Acid
      suppression is effective in preventing rebleeding from peptic ulcer. Standard
      doses of intravenous omeprazole may be as effective as high-dose regimens. Oral
      omeprazole also reduces rebleeding following endoscopic therapy for peptic ulcer.
      Mallory-Weiss tears result in significant bleeding in 23 % of cases. Endoscopic
      therapy may only be required in cases in which active bleeding is present.
      Endoscopic therapy is effective and safe in patients with major peptic ulcer
      bleeding who are over 80 years old. For peptic ulcer, injection of larger volumes
      of epinephrine (adrenaline; mean 16.5 ml) are more effective than small volumes
      (mean 8 ml). Injection of normal saline alone is less effective than bipolar
      electrocoagulation. The addition of fibrin glue to epinephrine injection does not
      confer an additional benefit over epinephrine alone. Argon plasma coagulation can
      be used to treat a range of lesions in the gastrointestinal tract. It is also
      effective for treatment of bleeding ulcer, but is no better than established
      methods. Haemoclips may be useful in bleeding Mallory-Weiss tears, but their use
      is difficult in patients bleeding from peptic ulcer. The presence of a large
      ulcer and active bleeding at the time of endoscopy are independent predictors of
      failure of endoscopic therapy.

PMID- 12510223
TI  - Colon polyps and cancer.
AB  - A large number of studies published last year in peer-reviewed medical journals
      help to better define the advantages and limitations of the different options for
      colorectal cancer screening. Direct colonoscopy screening appears to have the
      greatest potential to markedly reduce both the incidence and mortality of
      colorectal cancer, but many obstacles limiting its widespread use in the general
      at-risk population still exist, and many questions remain incompletely answered.
      Recent studies stress the fact that finding and resecting advanced adenomatous
      polyps, and thereby preventing cancer, is becoming a primary objective of
      screening programs. Several papers also show the potential of emerging new
      methods of screening for specific markers in stool and for imaging the colon with
      computed-tomographic colonography (virtual colonoscopy). Other important
      publications highlighted in this review deal with the diagnosis of colorectal
      neoplasia, familial colorectal cancer, colorectal polyps and the adenoma
      carcinoma sequence, and new and novel methods of improving the efficiency and
      safety of colonoscopic polypectomy.

PMID- 12510224
TI  - Diagnosis of esophagogastric tumors.
AB  - It has been suggested that certain histological criteria may serve to indicate a
      good prognosis in patients with esophageal carcinoma. These include absence of
      subepithelial extension of the carcinoma cells, stage no higher than m2, and no
      neoplastic involvement near the resection margin. As endoscopic mucosal resection
      is becoming an accepted treatment option in this type of tumor, prognostic
      parameters of this type are of particular interest. By contrast, when metastases
      are detected in the celiac lymph nodes, it implies that the tumor is unresectable
      and that palliative treatment is required. Endoscopic ultrasound (EUS)-guided
      fine-needle aspiration has been found to be the most cost-effective option in
      this setting. Although autofluorescence endoscopy is being tested as a new
      technique for endoscopic diagnosis, its value is at present unclear. However,
      such developments may lead to improved diagnosis in the future, particularly in
      relation to the initial stages of carcinoma. For the moment, EUS is still the
      most widely accepted method for early diagnosis and staging. Esophageal squamous
      cell carcinoma appears to be commonly associated with head and neck cancer, but
      the cost-effectiveness of surveillance is a matter of controversy. With regard to
      Barrett's esophagus and adenocarcinoma, p53 staining in areas of low-grade
      dysplasia appears to be helpful for predicting progression to high-grade
      dysplasia. The prevalence of short-segment Barrett's esophagus increases with
      age, but the length of the segment does not increase with time; the length
      probably depends on individual conditions, not merely on elapsed time.
      Helicobacter pylori infection appears to be associated with intestinal metaplasia
      at the esophagogastric junction. However, the most recent data appear to suggest
      that this scenario (usually termed "carditis") may be different from intestinal
      metaplasia in the lower esophagus, related to acid reflux. A follow-up program
      might be able to detect Barrett's esophagus adenocarcinoma at earlier stages, but
      only a minority of Barrett's esophagus patients are likely to be detected before
      neoplasia has developed. Gastric cancer appears to develop in individuals with H.
      pylori infection, but not in uninfected persons. In addition, those with severe
      gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia may be
      at greater risk for gastric cancer. This again raises the question of H. pylori
      eradication in asymptomatic individuals with infection, and surveillance of
      patients with severe intestinal metaplasia. The most recent data appear to
      support the notion that healing of MALT lymphoma depends not only on H. pylori
      eradication and on the stage of the tumor, but also on individual factors
      (possibly immunology-related).

PMID- 12510225
TI  - Diagnostic laparoscopy.
AB  - Diagnostic laparoscopy is increasingly being used to aid decision-making in the
      treatment of serious diseases. The majority of papers on the topic published
      during the last year have been concerned with preoperative assessment of
      malignant diseases of the gastrointestinal tract, and have shown that laparoscopy
      alone--or, even better, in combination with laparoscopic ultrasonography--is able
      to identify metastatic disease and therefore to reduce significantly the risk of
      unnecessary laparotomies. New techniques such as the application of fluorescent
      dyes may improve these results even further. Surgeons are increasingly using
      diagnostic laparoscopy in patients with acute abdomen and abdominal trauma--a
      minimally invasive strategy that should also be supported by gastroenterologists.
      Close cooperation between surgeons and gastroenterologists can also be promoted
      by using laparoscopy in critically ill patients in intensive-care units when a
      decision needs to be taken on whether or not laparotomy should be performed. The
      technique of diagnostic laparoscopy is returning to widespread use after a period
      of decline.

PMID- 12510226
TI  - Therapeutic pancreatic endoscopy.
AB  - The role of endoscopic retrograde cholangiopancreatography (ERCP) in the
      management of pancreatic diseases is continuing to evolve. This article reviews
      recent publications spanning a wide range of topics related to therapeutic
      pancreatic endoscopy: Over the last 12 months, several case series have added to
      the literature on the short-term and long-term effectiveness of endoscopic
      therapy of pseudocysts, pancreatic abscesses and fistulas. Identification of a
      communication between pancreatic duct and a pseudocyst has been suggested to
      predict response to percutaneous drainage. The importance of identifying
      pancreatic leaks in patients with severe pancreatitis has been stressed. In
      addition, endotherapy has been reported to be effective in patients with
      idiopathic chronic pancreatitis. Endoscopic removal of pancreatic stones after
      extracorporeal lithotripsy has been shown to result in long-term improvement in
      clinical outcomes in patients with chronic calcific pancreatitis. Other
      interesting publications addressed new techniques and tricks to achieve access to
      the difficult pancreatic duct. Finally, no review of pancreatic endotherapy would
      be complete without a reminder--as recently stated by a National Institutes of
      Health consensus panel--that there is considerable need for higher-quality and
      controlled trials in this and other areas of interventional endoscopy.

PMID- 12510227
TI  - Minilaparoscopy in the diagnosis of cirrhosis: superiority in patients with Child
      Pugh A and macronodular disease.
AB  - BACKGROUND AND STUDY AIMS: The diagnosis of cirrhosis has prognostic and
      therapeutic implications, but early forms are difficult to diagnose. Laparoscopy
      with histology has been reported to be superior to histology alone, but is often
      considered to be too invasive. This study aimed to assess whether minilaparoscopy
      offers similarly high sensitivity coupled with only minor invasiveness. PATIENTS
      AND METHODS: Minilaparoscopy with biopsy was performed in 226 consecutive
      patients with chronic liver disease. Cirrhosis was diagnosed macroscopically
      primarily on the basis of nodularity in a nontumorous liver. A histological
      diagnosis using the modified Knodell score was made without knowledge of the
      macroscopic assessment. RESULTS: Biopsies from 22 patients were inadequate for
      histological assessment, and 16 of these were considered to be cirrhotic from
      macroscopic observation. Out of 204 liver biopsies, 94 (46 %) were
      macroscopically identified as cirrhotic; 68/204 (33 %) showed stage 5 or 6
      fibrosis (incomplete or complete cirrhosis). Histological understaging occurred
      mainly in patients who were otherwise diagnosed as having early Child-Pugh A
      cirrhosis, macroscopically incomplete cirrhosis and macronodular cirrhosis; 4/204
      (2 %) of patients with cirrhosis histologically were understaged macroscopically.
      CONCLUSIONS: Macroscopic evaluation during minilaparoscopy increases the
      sensitivity of detection of liver cirrhosis, compared with biopsy alone, by more
      than 30 %. Because of its minimal invasiveness, minilaparoscopy combined with
      biopsy is recommended as a superior method for the staging of chronic liver
      disease.

PMID- 12510228
TI  - Even young patients with no alarm symptoms should undergo endoscopy for earlier
      diagnosis of gastric cancer.
AB  - BACKGROUND AND STUDY AIMS: There has been a tendency in recent years to omit
      endoscopy in dyspeptic patients younger than 45 years with no so-called "alarm
      symptoms." This study was conducted to test whether this policy might lead to an
      increased rate of delayed diagnosis of gastric cancer, especially in a population
      with a high prevalence of the disease. PATIENTS AND METHODS: The study included
      860 patients (465 women, 395 men; median age 44) referred for the first time for
      upper gastrointestinal endoscopy because of suspected upper gastrointestinal
      pathology, to a secondary referral center between 1983 and 1993. Symptoms were
      assessed using a special questionnaire prior to endoscopy. The endoscopic
      diagnosis was always confirmed by histology. RESULTS: Gastric cancer was found in
      83 patients (12 early cancers, 71 advanced). Patients with cancer were
      predominantly male (68 %, compared with 44 % in the no-cancer group; P < 0.001),
      and significantly older (median age 56, 44 and 42 years for advanced, early
      cancer, and no cancer, respectively; P < 0.001). As many as 24 % of patients with
      cancer were aged under 45 years. Symptoms occurring more frequently in the
      gastric cancer group compared with the no-cancer group were weight loss (11 % vs.
      0.1 %; P < 0.001), gastrointestinal bleeding (18 % vs. 8 %; P < 0.001), anorexia
      (43 % vs. 25 %; P < 0.001), and fatigue (53 % vs. 30 %; P < 0.001). In 27 % of
      cancer patients none of the above symptoms was observed. No statistical
      difference was seen for pain, nausea, vomiting, and other symptoms. The mean
      symptom score (1 point for one symptom) was higher in patients with cancer
      compared with those without (3.1 vs. 2.4; P < 0.001). The duration score (1 to 4
      points for durations of less than 6, less than 12, less than 24, and more than 24
      months) was lower (1.3 vs. 1.8; P < 0.001) in cancer patients. In three-quarters
      of cancer patients the duration of symptoms was shorter than 6 months.
      CONCLUSIONS: Symptoms suggesting gastric cancer are gastrointestinal bleeding,
      weight loss, and to a lesser degree anorexia and fatigue. Gastric cancer patients
      show a greater intensity but shorter duration of symptoms than patients with no
      cancer. Age and alarm symptoms cannot determine the need for upper
      gastrointestinal endoscopy, at least in areas of high prevalence of gastric
      cancer.

PMID- 12510229
TI  - Open-access endoscopy: are age-based guidelines justified? An audit of experience
      of 1000 open-access endoscopies at a district general hospital.
AB  - BACKGROUND AND STUDY AIMS: Open-access endoscopy has been developed to meet the
      increasing demand for endoscopy, and guidelines have been produced for selecting
      suitable patients. This study was designed to assess the appropriateness of these
      guidelines in patients referred to open-access endoscopy services at a district
      general hospital. PATIENTS AND METHODS: A series of 1000 consecutive patients
      referred for open-access endoscopy was audited. The waiting time was 18 weeks and
      patients continued to take any acid-suppressing medication prescribed by their
      general practitioner. The endoscopy findings were compared in those who met and
      did not meet currently accepted guidelines. In addition the outcome for all
      patients in whom gastro-oesophageal malignancy was detected was reviewed.
      RESULTS: 301 patients (30.1 %) did not meet accepted guidelines for open-access
      endoscopy. No cases of malignancy would have been missed if the guidelines had
      been implemented. Gastro-oesophageal malignancy was detected in 17 patients, all
      of whom died. When malignancy was excluded, there were no statistically
      significant differences between the detection rates for pathology in the two
      groups. The commonest finding, in 32.3 % of patients, was of a normal endoscopic
      appearance. CONCLUSIONS: If current guidelines are applied, all cases of
      malignancy may be picked up, but identification of patients with curable disease
      is poor. Use of the guidelines did not select patients with other upper
      gastrointestinal disease, although many patients were receiving acid-suppression
      therapy at the time of their endoscopy. Implementation of test-and-treat
      strategies would result in a significant reduction in the workload of open-access
      endoscopy.

PMID- 12510230
TI  - Minilaparoscopy for early diagnosis of cirrhosis: is the endoscopist's eye better
      than the histopathologist's?

PMID- 12510231
TI  - Is age a good discriminator when deciding whether to perform gastroscopy?

PMID- 12510232
TI  - Metal stents for tumors of the distal esophagus and gastric cardia.

PMID- 12510233
TI  - A case of multicentric gastric carcinoids without hypergastrinemia.
AB  - We have encountered an unusual case of gastric carcinoid tumors. Gastroscopic
      examination of a 71-year-old male patient showed eight smooth protrusions at the
      greater curvature of the gastric body, some of which had central depressions.
      Endoscopic ultrasonography demonstrated that the largest tumor (2.6 cm in
      diameter) was located in the submucosal layer. The patient had a normal serum
      gastrin level and was negative for antiparietal cell antibody. The patient was
      also found to have a pituitary tumor, an adenomatous goiter, and bilateral
      Warthin's tumors of the parotid glands. Histological examination of the resected
      stomach identified 12 discrete carcinoid tumors. There was no evidence of
      atrophic gastritis or of endocrine cell micronests. No mutations of the MEN1 gene
      were found on genomic DNA analysis. Despite the multiplicity of carcinoid tumors,
      we diagnosed type 3 gastric carcinoid in this patient.

PMID- 12510234
TI  - Magnetic resonance-guided biliary drainage in a patient with malignant
      obstructive jaundice and thrombocytopenia.
AB  - In a patient suffering from malignant obstructive jaundice and thrombocytopenia,
      magnetic resonance imaging (MRI) was used to guide percutaneous transhepatic
      biliary drainage, to avoid blind puncture of the bile ducts using fluoroscopy.
      The first puncture approach was successful, and an MRI-visible guide wire and
      drainage catheter were inserted successfully within 35 min. The course after the
      intervention was uneventful, and the patient's fever and itching improved. MRI
      guidance facilitated optimal procedure planning and high puncture accuracy.

PMID- 12510235
TI  - Primary vs. secondary common bile duct stones: apples and oranges.

PMID- 12510237
TI  - Mesenteric perforation of an obstructing sigmoid colon tumor after endoluminal
      stent insertion.

PMID- 12510238
TI  - Double guide wire placement for endoscopic pancreaticobiliary procedures.

PMID- 12510239
TI  - Placement of a biliary catheter in the pancreatic duct to aid common bile duct
      cannulation.

PMID- 12510240
TI  - The new Soehendra stent retriever makes stent exchange much easier.

PMID- 12510241
TI  - Capsule endoscopy appearances of small-bowel tuberculosis.

PMID- 12510242
TI  - Watermelon stomach seen by wireless-capsule endoscopy.

PMID- 12510243
TI  - Multiple cystic duct stones causing choledochal obstruction.

PMID- 12510244
TI  - [Deliberate self-poisoning with paracetamol (acetaminophen): an analysis from
      1995 to 2002].
AB  - BACKGROUND AND OBJECTIVE: Paracetamol is frequently used in deliberate self
      poisoning resulting in a major risk for the patients due to its dose-dependent
      hepatotoxicity. In the present study the cases of intoxications consulting our
      Poison Center should be analysed illustrating recent results and trends. PATIENTS
      AND METHODS: From 38 065 patients (25 098 female, 12447 male, 520 sex unknown,
      average age 36.8 years) registered during the study period from 1.1.1995 until
      31.5.2002 4021 with paracetamol intoxication were analysed with respect to the
      ingested dose, concomitant substances, the degree of observed symptoms and the
      length of hospital stay. RESULTS: The use of paracetamol in deliberate self
      poisoning continuously increased during the study period from 8.9 % in the year
      1995 to 12.4 % in 2002. Paracetamol was mainly used from female patients and
      patients in the age group between 10 and 29 years. 88.6 % of cases were reported
      to the poison center within the first twelve hours after ingestion. Concomitantly
      non-steroidal antirheumatics (38.0 %), ethanol (20.6 %) and antibiotics (15.0 %)
      were ingested. Monointoxications as well as mixed intoxications with paracetamol
      caused severe intoxications and deaths less frequently as compared to the group
      of the remainder substances with the degree of symptoms tended to be dose
      dependent. In 73.7 % of cases the length of hospital stay did not exceed 3 days.
      CONCLUSIONS: In recent years, an increasing importance of paracetamol in
      deliberate self-poisoning was determined particularly concerning female and
      younger patients. The dose of paracetamol and the duration of exposition are
      crucial for prognosis. With an early antidote therapy hospitalization is usually
      observed for a few days only. A risk for complications are frequently used
      concomitant substances requiring a detailed registration.

PMID- 12510245
TI  - [Determinants in the careers of male and female physicians from the viewpoint of
      chief physicians].
AB  - BACKGROUND AND OBJECTIVE: Chief physicians play an important role for physicians'
      careers by providing advanced training and allocating time and research
      resources. This study examined which characteristics will help physicians to
      achieve a leadership position and how chief physicians conduct career promotion.
      SAMPLE AND METHODS: All 532 chief physicians in Switzerland's German speaking
      cantons with medical schools were approached with a questionnaire covering
      professional motivation and personal attributes of career-oriented physicians
      career-promoting personal and institutional factors, and type of career
      promotion. RESULTS: 207 chief physicians (189 men, 18 women; participation rate
      38.9 %;) participated. Respondents rated achievement motivation combined with
      professional interest and job enjoyment (intrinsic), and interest in advancement
      and social prestige (extrinsic motivation) as beneficial. Extraprofessional
      concerns such as family obligations and leisure interests were viewed as less
      important. Instrumental attributes were rated as advantageous. Expressive
      qualities were also seen as beneficial but less crucial. Ratings were independent
      of respondents' age, specialty, or type of workplace. The following personal
      factors were named: professional commitment, professional and social competence,
      goal orientation, endurance, and strength of character. The institutional factors
      referred to quality of training and teaching, a good work atmosphere, a
      transparent and flexible clinic structure. Career promotion was offered
      predominantly in the form of coaching, career planning, and support in job
      search. CONCLUSION: Career promotion should be more targeted and structured, e.
      g. be conducted in mentoring programmes, thus providing the prerequisites for a
      truly equal career promotion of female and male physicians.

PMID- 12510246
TI  - [Sudden cardiac death in a case of systemic sarcoidosis].
AB  - CLINICAL PRESENTATION: A 55-year-old woman required emergency medical care
      because of sudden weakness. On arrival of the emergency physician the patient
      presented with bradycardia with a normal rhythm. The blood pressure was not
      measurable. The patient complained of recurrent dizziness for a few months.
      Subsequently, the patient presented with an asystole and required reanimation and
      insertion of a temporary cardiac pacemaker. On admission at the hospital
      myocardial infarction was suspected. CLINICAL AND LABORATORY TESTS: At the time
      of admission the patient presented in cardiogenic shock. The ECG revealed a 3rd
      atrioventricular block with idioventricular rhythm. Echocardiography showed
      reduced left ventricular function with global hypokinesia of the myocardium.
      Coronary artery disease was excluded by angiography. To exclude acute pulmonary
      embolism a CT-scan of the thorax was performed, revealing enlarged lymph nodes in
      the mediastinum. TREATMENT AND RESPONSE TO THERAPY: Despite the administration of
      high-dose catecholamines and before a left atrial-to-femoral arterial assist
      device could be completely implanted the patient died of cardiogenic shock.
      AUTOPSY: Autopsy revealed non-caseating epitheloid granulomas in the enlarged
      mediastinal lymph nodes as well as in the lung parenchyma, myocardium and several
      other organs. CONCLUSION: The cardiac involvement of previously undiagnosed
      systemic sarcoidosis was the cause of sudden death. In case of ECG changes of
      unknown cause in persons without a history of structural cardiac disease
      sarcoidosis should be considered in the differential diagnosis.

PMID- 12510247
TI  - [Coronary angiography by magnetic resonance imaging and computed tomography].

PMID- 12510248
TI  - [Non-surgical therapy of iatrogenic false aneurysms].
AB  - SUMMARY: False aneurysms occur after 0.1 - 1.5 % of all diagnostic and up to 6 %
      of all therapeutic percutaneous interventions. Surgery used to be the treatment
      of choice in symptomatic patients. But two non-invasive measures of treatment
      gain more attention: ultrasound guided compression (UGC) and ultrasound guided
      thrombin injection (UGTI). UGC with compression times from 30 - 120 min is
      effective in 80 % of patients without anticoagulation. However, UGC is often
      painful and results in prolongation of in-hospital time. UGTI is effective in 95
      % of patients. Usually, 100 - 2000 U of thrombin are injected into the false
      aneurysm. UGTI is also effective in the presence of anticoagulation or
      antiplatelet therapy. UGTI is not indicated in patients with a large
      communication with the native vessel and in arterio-venous-fistulas. In patients
      with large haematomas, ongoing bleeding, damage of the native vessel, compression
      of arteries, veins or neurological deficits, or with infections, early surgical
      repair is still the treatment of choice.

PMID- 12510249
TI  - Treatment of arteriosclerosis.
AB  - Summary. Arteriosclerotic disease develops over the course of several decades.
      Currently, a number of therapies are at hand to effectively stop this process and
      avoid complications of arteriosclerosis. Among the non-pharmacologic options, a
      balanced diet and physical activity predominate. A modern dietary plan offers a
      variety of tasty servings rich in fresh fruit and vegetables, cereals, fish, and
      poly-unsaturated fatty acids. The value of regular physical activity is
      demonstrated by the finding that an increase in exercise capacity
      ("cardiorespiratory fitness") by only one metabolic equivalent already reduces
      cardiovascular risk by 20-25 %. Regarding pharmacologic therapy, convincing data
      are available for cholesterol synthase inhibitors ("statins"), some substances
      which influence the renin-angiotensin system (such as ramipril), and platelet
      aggregation inhibitors. Statins produce a 20 to 30 % reduction of cardiac death,
      myocardial infarction, and stroke. In patients with increased cardiovascular
      risk, the beneficial action of statins is also evident in subjects with low
      baseline cholesterol values. Apart from the cholesterol-lowering effects, anti
      inflammatory and other vasoprotective mechanisms are involved. The angiotensin
      converting enzyme inhibitor ramipril has demonstrated that even independent of
      blood-pressure lowering, cardiovascular events (cardiac death, myocardial
      infarction, stroke) are substantially reduced in high-risk patients. The effect
      is in the same order as that of statins. In patients with left-ventricular
      hypertrophy, the angiotensin-receptor antagonist losartan produces a notable
      reduction in stroke, independent of its blood-pressure lowering action. Finally,
      the platelet aggregation inhibitors aspirin and clopidogrel have proven benefit
      in secondary prevention and, in the case of aspirin, also in primary prevention
      in cardiovascular high-risk patients. The anti-arteriosclerotic properties of
      other substances are actively investigated, including calcium channel blockers,
      betablockers, and novel drug classes. From the medical point of view, a broader
      use of the well-proven and effective therapies of arteriosclerosis and its
      complications is clearly warranted.

PMID- 12510250
TI  - [Transmission of hepatitis B infection from the mother to the newborn].

PMID- 12510251
TI  - Reliability of different techniques to assess marginal defects of Class II
      restorations in retrieved primary molars: a visual-tactile, SEM, dye penetration
      and polarized light microscopy study.
AB  - The aims of the present article were to assess the reliability of different
      techniques to assess marginal defects in Class II restorations in retrieved
      primary molars, and to determine the degree of agreement between the various
      assessment modalities. The material evaluated was comprised of 18 exfoliated
      primary molars that had been restored 20 to 22 months previously with a resin
      modified glass ionomer (Vitremer--7 teeth), a hybridized composite resin (Z100 +
      Scotchbond Multipurpose--9 teeth), and amalgam (Dispersalloy--2 teeth). No
      significant differences could be observed between the groups. The majority of the
      restorations rated A at the buccal and lingual margins, but poor adaptation was
      disclosed at the cervical margin of the three types of restorations. SEM
      evaluation revealed that the highest percentage of defects was seen at the
      cervical margins with no statistically significant difference between the groups.
      No or minimal leakage was present at the occlusal margins and severe penetration
      of dye was seen at the cervical margins in all groups. Significantly less
      demineralization was seen adjacent to the Vitremer and Z100 restorations when
      compared to the Dispersalloy but no difference was found between the esthetic
      restorations. Except for the visual tactile examination, small marginal defects
      could be disclosed by the three assessment techniques (SEM, dye penetration, and
      polarized light microscopy). A good degree of agreement was observed between the
      three evaluation techniques.

PMID- 12510252
TI  - [Implant fracture: a complication of treatment with dental implants--review of
      the literature].
AB  - Dental implants are a functional and esthetic solution to partial and total
      edentulism. The initial success rate of this treatment modality is 90-95%. But,
      that treatment modality is not free of complications. One of the rare
      complications yet, with severe clinical results is fracture of dental implants.
      The current literature review presents the various causative factors that may
      lead to implant fracture. Implant failures may be sorted into groups by the
      timing of their appearance, or by the origin of failure. Fractures belong to the
      group of late complications, caused by a biomechanical overload. Overload may be
      caused by inappropriate seat of the superstructure, in-line arrangement of the
      implants, leverage, heavy occlusal forces (bruxing, clenching), location of the
      implant and the size of the implant or metal fatigue. Good clinical examinations
      and correct treatment plans may reduce the risk of implant fracture.

PMID- 12510253
TI  - [Gingival depigmentation for aesthetic purposes using erbium:YAG laser: rationale
      and technique].
AB  - Melanin, carotene and hemoglobin are the most common natural pigments
      contributing to the normal color of the gums. Although physiologic and ethnic
      melanin pigmentation is not a medical problem, complains about "black gums" are
      common. Gingival depigmentation has been carried out using surgical, chemical,
      electrosurgical and cryosurgical procedures. Recently, Laser Ablation has been
      recognized as one of the most effective, pleasant and reliable techniques.
      Effective depigmentation of the gingival requires removal of all or most of the
      melanocytes from the basal layer of the gingival epithelium. Using non-specific
      radiation means ablation of all the epithelial cell layers, as well as connective
      tissue rete pegs, leaving behind only remnants of the epithelial rete ridges.
      CO2, Nd:YAG and Erbium:YAG lasers, meeting most of these requirements and being
      available in the dental office, seems to be the lasers of choice for this
      procedure. Five patients (3 F; 2 M) who were referred to the TAUSDM for cosmetic
      therapy of "black gums" were treated using Erbium-YAG laser. The laser beam was
      set up at 850 mj/10 pulses per second producing peak power of 2.13 kwand peak
      power density of 30.43 kw/sq/cm. The beam was defocused to produce a 3 mm
      diameter circle, thus reducing the beam penetration while increasing the treated
      surface. Using the "brush" technique, 800-2,000 pulses were required per patient,
      with an average of 500-1,100 pulses per 1 sq.cm, depending on the thickness of
      the epithelium and the intensity of the pigmentation. Treatment required only
      topical anesthesia. Healing was uneventful and required no supportive therapy.
      Three months follow up has shown no repigmentation in any of the patients.
      Patients' evaluation analysis showed that the results were pleasing; no pain was
      experienced during lasing as well as during healing. Two patients were interupted
      by the lasing burning smell, which may be reduced or eliminated by operating a
      power suction during the procedure.

PMID- 12510254
TI  - [Medical treatment of central giant cell granuloma of the jaws].
AB  - Central giant cell granuloma (CGCG) is a benign intraosseous lesion of the jaws
      that is found predominantly in children and young adults. The lesion appears
      mostly in the mandible and presents as a unilocular or multilocular radiolucent
      defect. Although it is benign, it may be locally aggressive, causing extensive
      bone destruction, tooth displacement and root resorption. Two variants of the
      lesion, non-aggressive and aggressive, have been described. Traditionally, CGCG
      was treated surgically with aggressive curettage and peripheral ostectomy. The
      more aggressive type or recurrent lesions require wide resection, that lead to
      major defects in the jaws. This form of surgical treatment could be particularly
      disfiguring for a child or young adult. An alternative, non-surgical approach,
      was developed during the past several years. The present review describes several
      medical treatments available for CGCG that have been reported in the literature,
      such as corticosteroids, calcitonin and Interferon Alfa-2a. These alternatives
      are advantageous for large aggressive lesions in order to cure, or reduce the
      size of the lesion and thus minimize the need for extensive surgical resection
      that could result in functional and esthetic deficits.

PMID- 12510255
TI  - [Techniques for immediate restoration of teeth following root canal therapy].
AB  - It is incumbent upon the dentist to restore the form and function of
      endodontically treated teeth. Different approaches and materials are described in
      the literature for restoring the missing tooth structure, either with a cast post
      and core or immediately with a chair-side post and core system. This article
      briefly reviews the available data regarding the microbiological, prosthetic,
      mechanical, and periodontal aspects while emphasizing the immediate approach
      using amalgam, composite and glass ionomer materials. The factors affecting
      retention of the post are presented to guide the clinician in selecting a
      suitable post and core system in preserving optimal root structure to prevent
      root fracture. Two clinical cases are presented in which tooth structure was
      restored using two techniques: in one, a provisional acrylic resin shell was used
      to house a dowel coronal-radicular amalgam core material, the other used a copper
      band for a composite post and core system. Both cases emphasize the ease of
      production and the short chair-time in the stages of crown fabrication.

PMID- 12510256
TI  - Early childhood caries (ECC)/baby-bottle tooth decay--a reminder.

PMID- 12510257
TI  - Eliminating microgaps: the PerioSeal Implant System. Interview.

PMID- 12510258
TI  - Porous materials via nanocasting procedures: innovative materials and learning
      about soft-matter organization.
AB  - Nanocasting, the 3D-transformation of self-assembled organic nanostructures into
      hollow inorganic replicas under preservation of fine structural details has
      recently turned out to be a versatile tool, both for the synthesis of porous
      media with new pore topology as well as for the characterization of the assembled
      structures themselves. This review gives a review on recent work describing the
      potential and restrictions of nanocasting using surfactants, polymers, colloids
      as well as supramolecular tectons as porogens.

PMID- 12510259
TI  - Cascade energy transfer in a conformationally mobile multichromophoric dendrimer.
AB  - A conformationally flexible, generation-2,3 poly(aryl ether) dendrimer favors
      quantitative cascade fluorescence resonance energy transfer without the
      appearance of undesired chromophore self-quenching interactions such as excimer
      formation.

PMID- 12510260
TI  - Simple tricyclohexylphosphine-palladium complexes as efficient catalysts for the
      Stille coupling of deactivated aryl chlorides.
AB  - Simple, inexpensive tricyclohexylphosphine adducts of palladium show the highest
      activity yet observed in the Stille coupling of non-activated and deactivated
      aryl chlorides.

PMID- 12510261
TI  - Extremely high activity catalysts for the Suzuki coupling of aryl chlorides: the
      importance of catalyst longevity.
AB  - The incorporation of a new pi-acidic, orthometallated phosphite ligand into a
      palladium pre-catalyst gives considerably enhanced catalyst longevity and thus
      extremely high activity in the Suzuki coupling of deactivated, activated and
      sterically hindered aryl chloride substrates.

PMID- 12510262
TI  - Resorcin[6]arene as a building block for tubular crystalline state architectures.
AB  - A resorcin[6]arene with an r-trans-cis-trans-cis-trans configuration of the
      pendant ethyl groups forms tubular crystal structures.

PMID- 12510263
TI  - Early-late transition metal ferromagnetic coupling mediated by hydrogen bonding.
AB  - Hydrogen bonding between early and late transition metal complexes is proposed as
      a strategy to obtain ferromagnetic interactions based on a theoretical study
      using density functional calculations.

PMID- 12510264
TI  - Permselective monolayer membrane based on two-dimensional cross-linked
      polysiloxane LB films for hydrogen peroxide detecting glucose sensors.
AB  - Novel two-dimensional (2D) cross-linked polysiloxane LB films were prepared and
      applied for glucose sensing as H2O2-permselective films in order to block other
      electroactive interferences, such as L-ascorbic acid, L-cysteine, uric acid and
      acetaminophen; the 2D cross-linked polysiloxane monolayers were remarkably
      effective in eliminating interfering responses and had a rapid response for
      glucose, even though the films were only a monolayer thick.

PMID- 12510265
TI  - Synthesis and reactivity of the imidotungsten methyl cation [W(N2Npy)(NPh)Me]+:
      CO2 adds to the W=NPh bond and does not insert into the W-Me bond.
AB  - The imidotungsten dimethyl compound [W(N2Npy)(NPh)Me2] 2 reacts with BArF3 to
      form the cationic complex [W(N2Npy)(NPh)Me]+ 3+ [anion = [MeBArF3]-; ArF = C6F5;
      N2Npy = MeC(2C5H4N)(CH2NSiMe3)2] which undergoes methyl group exchange with added
      2, [Cp2ZrMe2] or ZnMe2; treatment of cation 3+ with CO2 or isocyanates leads to
      cycloaddition reactions at the W=NPh bond and not insertion into the W-Me bond,
      despite the latter product being the most thermodynamically favourable according
      to DFT calculations.

PMID- 12510266
TI  - Selenocysteine-mediated backbone cyclization of unprotected peptides followed by
      alkylation, oxidative elimination or reduction of the selenol.
AB  - An unprotected 16 residue peptide containing a C-terminal thioester and an N
      terminal selenocysteine residue efficiently cyclizes in the presence of
      thiophenol; subsequent reduction, elimination or alkylation of the selenol yields
      modified cyclic peptides with alanine, dehydroalanine or a non-natural amino acid
      at the site of ligation.

PMID- 12510267
TI  - Nitrogen extrusion from pyrazoline-substituted porphyrins and chlorins using long
      wavelength visible light.
AB  - Protoporphyrin reacts with diazomethane to give pyrazolines which at long
      wavelength (approximately 630 nm) extrude nitrogen to give the corresponding
      cyclopropyl derivatives.

PMID- 12510268
TI  - Synthesis of 13C-labelled, bicyclic mimetics of natural enediynes.
AB  - Using a versatile synthesis with 13CH3PPh3I and CH(3)13CO2Et as 13C sources, the
      first examples of nine-membered chromophores which have been differentially
      labelled with 13C in their carbocyclic enediyne cores are described.

PMID- 12510269
TI  - One-pot synthesis of tropinone by tandem (domino) ene-type reactions of acetone
      silyl enol ethers.
AB  - A synthetic approach for tropane alkaloids on the basis of tandem (domino) ene
      type reactions of acetone silyl enol ethers with iminium ions is shown to be
      triggered by intermolecular ene-type reactions followed by 6-(2,5) silatropic ene
      type cyclizations.

PMID- 12510270
TI  - Novel template effect for the preparation of [2]rotaxanes with functionalised
      centre pieces.
AB  - A novel anion-templated synthesis permits the preparation of [2]rotaxanes with a
      tetralactam wheel through which axles are threaded that are functionalised at
      their center pieces; the wheel protects these groups efficiently against
      modifications.

PMID- 12510271
TI  - Accelerating water exchange for GdIII chelates by steric compression around the
      water binding site.
AB  - The water exchange process was accelerated for nine-coordinate, monohydrated
      macrocyclic GdIII complexes by inducing steric compression around the water
      binding site; the increased steric crowding was achieved by replacing an ethylene
      bridge of DOTA4- by a propylene bridge; in addition to the optimal water exchange
      rate, the stability of [Gd(TRITA)(H2O)]- is sufficiently high to ensure safe
      medical use which makes it a potential synthon for the development of high
      relaxivity, macromolecular MRI contrast agents.

PMID- 12510272
TI  - New materials based on renewable resources: chemically modified expanded corn
      starches as catalysts for liquid phase organic reactions.
AB  - Catalytically active chemically modified expanded corn starches have been
      developed with site loadings and activities comparable or superior to traditional
      materials.

PMID- 12510273
TI  - cis-stereoselective nickel-catalyzed cyclization/alkylation and arylation
      reactions of allenyl-aldehydes and -ketones with organozinc reagents.
AB  - Highly stereoselective alkylative and arylative cyclization reactions of allenyl
      aldehydes and -ketones with organozinc reagents occur efficiently in the presence
      of catalytic Ni(COD)2 to afford cis-fused homoallylic cyclopentanols.

PMID- 12510274
TI  - Novel generation of an o-quinone methide from 2-(2'-cyclohexenyl)phenol by
      excited state intramolecular proton transfer and subsequent C-C fragmentation.
AB  - Formation of an o-quinone methide via C-C fragmentation of a zwitterion formed by
      intramolecular excited state proton transfer from an o-allylphenol derivative is
      reported for the first time.

PMID- 12510275
TI  - Cathodically activated nucleophilic aromatic substitution of hydrogen: a novel
      electrochemical mechanism.
AB  - Cathodically activated nucleophilic aromatic substitution of hydrogen (SNArH) is
      reported for the first time; the 1,3,5-trinitrobenzene radical anion reacts with
      the nucleophile N-methylformamide leading to high yields of the sigma H-complex
      radical anion; this intermediate can be easily oxidised electrochemically by
      means of a three-electron mechanism giving rise to the nucleophilic aromatic
      substitution product (NASH product) in good yield.

PMID- 12510276
TI  - A novel compound with an interpenetrating 2D network structure constructed by
      [Mo5P2O23] and Ni-4,4'-bipyridine components: its synthesis, characterization and
      magnetic behaviour.
AB  - A Novel compound (Hbpy)2[[(H2O)3Ni(bpy)0.5Ni(bpy)(H2O)4]2[Mo5P2O23]
      [Ni((bpy)0.5)2(H2O)2][Mo5P2O23]].8H2O 1 (bpy = 4,4'-bipyridine) with an
      interpenetrating 2D network structure was synthesized hydrothermally and
      characterized by elemental analyses, IR, X-ray single crystal structure analysis
      and temperature-dependent magnetic susceptibility.

PMID- 12510277
TI  - Synthesis and crystal structure of 2,3,12,13-tetraalkoxy-21, 23-dithiaporphyrins.
AB  - 21,23-Dithiaporphyrins with methoxy, butoxy, octyloxy and dodecyloxy substituents
      at beta-thiophene carbons were synthesised for the first time and the crystal
      structure of the butoxy derivative indicated that the substituents at the beta
      thiophene carbons induce more planarity in the porphyrin ring.

PMID- 12510278
TI  - A non-classical hydrogen bond in the molybdenum arene complex [eta 6
      C6H5C6H3(Ph)OH]Mo(PMe3)3: evidence that hydrogen bonding facilitates oxidative
      addition of the O-H bond.
AB  - Mo(PMe3)6 reacts with 2,6-Ph2C6H3OH to give the eta 6-arene complex [eta 6
      C6H5C6H3(Ph)OH]Mo(PMe3)3 which exhibits a non-classical Mo...H-OAr hydrogen bond;
      DFT calculations indicate that the hydrogen bonding interaction facilitates
      oxidative addition of the O-H bond to give [eta 6,eta 1-C6H5C6H3(Ph)O]Mo(PMe3)2H.

PMID- 12510279
TI  - A chromoreactand for the selective detection of HSO3- based on the reversible
      bisulfite addition reaction in polymer membranes.
AB  - A new chromoreactand for the reversible optical detection of bisulfite anion is
      presented with a sensitivity in the range from 0.1 to 10 mM while no absorbance
      changes are observed for anions such as sulfate, chloride, phosphate or
      hydroxide.

PMID- 12510280
TI  - Redox switchable NIR dye derived from ruthenium-dioxolene-porphyrin systems.
AB  - Newly synthesised Ru(bp)2(sq)(+)-derivatives, covalently linked to a porphyrin
      core, show very high epsilon values in the NIR region; which exhibit fast on/off
      switching depending on the redox state of the coordinated dioxolene
      functionality.

PMID- 12510281
TI  - Ratiometric direct detection of nitric oxide based on a novel signal-switching
      mechanism.
AB  - A novel fluorescent probe, which could be the first example of a ratiometric
      molecular probe for direct monitoring of NO production, has been developed using
      a 'spin-exchange' mechanism.

PMID- 12510282
TI  - A two-dimensional molecular network structure of trimesic acid prepared by
      adsorption-induced self-organization.
AB  - A two-dimensional molecular network of trimesic acid on Au(111) was visualized by
      in situ scanning tunneling microscopy with submolecular resolution. The
      supramolecular structures including an 'order to order' phase transition were
      constructed by precise potential-controlled adsorption based on adsorption
      induced self-organization.

PMID- 12510283
TI  - Synthesis of nopol over MCM-41 catalysts.
AB  - MCM-41 was found to be an active heterogeneous catalyst for the synthesis of
      nopol by the Prins condensation of beta-pinene and paraformaldehyde, but Sn-MCM
      41 in which Sn has been grafted on MCM-41 by chemical vapor deposition is far
      more active and combines high efficiency and recyclability.

PMID- 12510284
TI  - N-substituent effect on the cis-trans geometry of nine-membered lactams.
AB  - The cis-trans geometry of a nine-membered lactam significantly depends on the N
      substituents; N-acyl-1-aza-2-cyclononanones (1a-c) exist as cis form; in
      contrast, N-Z- 1-aza-2-cyclononanone (1d) exists as trans form both in the
      crystal and in solution.

PMID- 12510285
TI  - Detection of complementary hydrogen bond complexes in water by electrospray
      ionization-Fourier-transform ion cyclotron resonance mass spectrometry.
AB  - Complementary base paired complex formation of a thymidine-appended
      bolaamphiphile with adenosine derivatives was able to be detected with high
      resolution and high sensitivity in aqueous solutions by electrospray ionization
      Fourier-transform ion cyclotron resonance mass (ESI-FTICR MS) spectrometry.

PMID- 12510286
TI  - Simultaneous occupation of SI and SI' cation sites in dehydrated zeolite LSX.
AB  - Simultaneous occupation of adjacent SI (or SIa) and SI' sites is calculated to be
      favourable in dehydrated zeolite K-LSX (supporting the experimental work of
      Paillaud et al.), although such a configuration is unlikely in other dehydrated
      LSX zeolites.

PMID- 12510287
TI  - Cooperative sulfate binding by metal salt extractants containing 3
      dialkylaminomethylsalicylaldimine units.
AB  - The pH-dependence of simultaneous metal- and sulfate-loading of simple salen
      derivatives demonstrates the feasibility of their application as extractants for
      recovery of base metals from the leaching of sulfidic ores. The efficacy of the
      ligands depends on the templating of the sulfate binding site by the attendant
      metal ion.

PMID- 12510288
TI  - Two-point contact chiral distinction--a theoretical appraisal.
AB  - Ab initio calculations reveal chiral distinction in two-point contact CHFCIBr
      dimers, with chiral distinction energy of 1.5 kJ mol-1 between the SR and SS
      dimers fully optimized at the MP2/6-311++G** level.

PMID- 12510289
TI  - Synthesis of high purity single-walled carbon nanotubes in high yield.
AB  - A simple method for the synthesis of high purity single wall carbon nanotubes has
      been developed by using nickel formate as a precursor for the formation of nearly
      mono-dispersed nickel seed-nanoparticles as catalysts in the CVD growth process.

PMID- 12510290
TI  - Efficient and regioselective synthesis of functionalized pyrroles by
      cyclocondensation of 1,3-dicarbonyl dianions with alpha-azidoketones.
AB  - The cyclocondensation of 1,3-dicarbonyl dianions with alpha-azidoketones
      regioselectively afforded 2-alkylidenepyrrolidines which were transformed into
      functionalized pyrroles by treatment with acid.

PMID- 12510291
TI  - Preparation and regioselective reactions of novel gem-difluorinated vinyloxiranes
      with some organometallic reagents.
AB  - Hitherto unknown, relatively labile gem-difluorinated vinyloxiranes were prepared
      by difluoro-Wittig reactions with alpha,beta-epoxyketones; for these
      vinyloxiranes alkyl groups were delivered at the fluorine-attached terminal
      carbon atom in an SN2' manner by RLi, while Me3Al and MeMgBr-CuCl (3: 1)
      introduced the Me group at the allylic epoxy carbon with retention and inversion
      of the original stereochemistry, respectively.

PMID- 12510292
TI  - The first tridentate phosphine ligand combining planar, phosphorus and carbon
      chirality.
AB  - Two new diastereomerically pure tridentate phosphine ligands combining planar,
      phosphorus and carbon chirality have been conveniently synthesized via resolution
      of their phosphineoxide-diborane adducts and structurally characterized by X-ray
      analyses.

PMID- 12510293
TI  - Low-cost and facile synthesis of mesocellular carbon foams.
AB  - Mesocellular carbon foam composed of nanometer sized primary particles was
      synthesized using hydrothermally synthesized MSU-F silica as a template and
      poly(furfuryl alcohol) as a carbon source.

PMID- 12510294
TI  - Enzymatic synthesis of beta-mannosyl phosphates on solid support.
AB  - Synthetic bifunctional analogues 4a, b and 14 of dolichol phosphate 1 were
      attached to solid support and were shown to be substrates for Dol-P-Man synthase.

PMID- 12510295
TI  - Photocatalytic degradation of hexachlorocyclohexane (HCH) by TiO2-pillared
      fluorine mica.
AB  - A significant effect of clay host was observed on the photocatalytic activity of
      TiO2; TiO2-pillared fluorine mica exhibited two orders of magnitude higher
      activity than TiO2 and TiO2-pillared montmorillonite for the photocatalytic
      degradation of gamma-HCH.

PMID- 12510296
TI  - Use of gel-casting to prepare HPLC monolithic silica columns with uniform
      mesopores and tunable macrochannels.
AB  - Monolithic silica columns with defined mesopore and a tunable macropore structure
      were fabricated by the gel-casting of ordered mesoporous silica precursors.

PMID- 12510297
TI  - A novel organometallic columnar complex containing endohedral silver(I)
      ethynediyl binding and exterior silver(I)-aromatic interaction.
AB  - Unprecedented eta 3 pi-donor behavior of the benzyltrimethy-lammonium ion is
      observed in the polymeric silver(I) complex [(PhCH2NMe3)Ag7(C2)(CF3CO2)6]n that
      comprises a columnar backbone constructed from the fusion of Ag8 square
      antiprisms each enclosing an acetylide dianion.

PMID- 12510298
TI  - Enzymatic silicone oligomerization catalyzed by a lipid-coated lipase.
AB  - A lipid (1)-coated lipase can catalyze the oligomerization of
      diethoxydimethylsilane (DEDMS) in isooctane containing 2wt% water, where the
      polymerization occurs at the OH group of the coating lipid (1) in the enzyme
      cavity.

PMID- 12510299
TI  - G-quadruplex as a new class of structural entities for directing the formation of
      circular oligodeoxyribonucleotides.
AB  - It has been demonstrated for the first time that G-quadruplex is capable of
      acting as a template for directing the sequence-specific formation of certain
      circular oligodeoxyribonucleotides with high efficiency.

PMID- 12510300
TI  - Crystallographic characterization of isomer 2 of Er2@C82 and comparison with
      isomer 1 of Er2@C82.
AB  - The X-ray crystal structure of (Isomer 2 of Er2@C82). NiII(OEP).2(benzene) shows
      that the fullerene cage in Isomer 2 of Er2@C82 is the C3v isomer (82:8) and that
      the erbium ions are distributed over 23 interior sites with occupancies ranging
      from 0.25 to 0.03.

PMID- 12510301
TI  - Efficient synthesis of 3,4-ethylenedioxythiophenes (EDOT) by Mitsunobu reaction.
AB  - Using the Mitsunobu reaction as a key step, a general and efficient method for
      the synthesis of EDOT monomers has been developed. Novel substituted EDOTs and
      the first chiral derivatives were generated in high yields.

PMID- 12510302
TI  - Unprecedented host-induced intramolecular charge-transfer complex formation.
AB  - For the first time, host-induced intramolecular charge-transfer complex formation
      in a guest containing both an electron donor and an electron acceptor is
      demonstrated in the cucurbit[8]uril cavity, leading to unusual back-folding of
      the guest molecule.

PMID- 12510303
TI  - A highly active Fe(I) catalyst for radical polymerisation and taming the
      polymerisation with iodine.
AB  - A fast and controlled radical polymerisation of acrylates and acrylamides can be
      achieved with a combination of a highly active metal catalyst, Fe2Cp2(CO)4, and a
      mild radical scavenger, iodine, in the presence of an iodide initiator.

PMID- 12510304
TI  - Enantioselective epoxidation of olefins catalyzed by Mn (salen)/MCM-41
      synthesized with a new anchoring method.
AB  - New immobilization of the chiral Mn(salen) complex through the complexation of
      managanese by oxygen atoms of the phenoxyl groups grafted on the surface of MCM
      41 leads to a markedly higher ee than for the free complex.

PMID- 12510305
TI  - Molecular imprinting of bisphenol A and alkylphenols using amylose as a host
      matrix.
AB  - A novel molecularly imprinted polymer has been created by a radical
      polymerisation of acryloylamylose in the presence of a template.

PMID- 12510306
TI  - Dendritic effect in polymer-supported catalysis of the intramolecular Pauson
      Khand reaction.
AB  - A remarkable increase in catalytic activity and selectivity in the intramolecular
      Pauson-Khand reaction is observed for Co complexes, immobilised on second- and
      third-generation dendron-functionalized polystyrene, as compared with their
      analogues on non-dendronized support.

PMID- 12510307
TI  - Synthesis of hexagonal and cubic super-microporous niobium phosphates with anion
      exchange capacity and catalytic properties.
AB  - Super-microporous hexagonal niobium phosphate synthesized using neutral
      surfactant (S0I0 mechanism) and cubic structure with cationic surfactant (S+X
      I+); the hexagonal niobium phosphate possesses an excellent anion exchange
      capacity (6.3 mmol g-1) and high product selectivity towards 4-naphthaquinone
      (88.6%) in the oxidation of 1-naphthol in presence of aqueous H2O2.

PMID- 12510308
TI  - Oxazolines as chiral building blocks for imidazolium salts and N-heterocyclic
      carbene ligands.
AB  - Enantiomerically pure imidazolium triflates can be readily prepared from
      bioxazolines and oxazolineimines; deprotonation of imidazolium triflate 2 gives a
      chiral N-heterocyclic carbene that can act as a ligand in a catalytically active
      palladium complex.

PMID- 12510309
TI  - Solubility of cerium in LaCoO3-influence on catalytic activity.
AB  - The recent interest in the catalytic properties of lanthanum perovskites for
      methane combustion and three way catalysis has led to considerable debate as to
      their structure and defect chemistry. We have investigated the doping of LaCoO3
      with the tetravalent cerium cation using atomistic simulation techniques. We have
      compared three routes for cerium insertion and identified the favoured doping
      mechanism, which explain experimental observations relating to the effect of
      cerium on catalytic activity.

PMID- 12510310
TI  - A paradigm for biological sulfur transfers via persulfide groups: a persulfide
      disulfide-thiol cycle in 4-thiouridine biosynthesis.
AB  - In support of the key features of sulfur transfer in the proposed mechanisms of 4
      thiouridine generation, the enzyme ThiI can turn over only once in the absence of
      reductants of disulfide bonds, and Cys-456 of ThiI receives the sulfur
      transferred from the persulfide group of the sulfurtransferase IscS.

PMID- 12510311
TI  - Dialkyl aluminium amides: new reagents for the conversion of C=O into C=NR
      functionalities.
AB  - A new methodology for the preparation of alpha-diimines and beta-aminoenones has
      been devised and represents an alternative route to these and related nitrogenous
      ligands bearing highly electronegative substituents.

PMID- 12510312
TI  - Alternate stranded triplex formation of chimeric DNA composed of tandem alpha-
      and beta-anomeric strands.
AB  - A chimeric oligoDNA composed of a natural beta-anomeric oligonucleotide portion
      and an unnatural alpha-anomeric oligonucleotide portion forms an alternate
      stranded triplex possessing enhanced thermal stability compared to the triplexes
      composed of the parental oligomers.

PMID- 12510313
TI  - Preparation and electrochemical polymerization of new multifunctional
      pyrrolethiolate-stabilized gold and palladium nanoparticles.
AB  - New pyrrolylalkanethiolate-stabilized gold and palladium nanoparticles have been
      prepared: electrochemical polymerization of their metal nanoparticles and their
      TEMPO-derivatized metal nanoparticles gave the remarkably stable poly(pyrrole
      metal nanoparticle) films on metal electrodes.

PMID- 12510314
TI  - A novel 2-D interlinking zigzag-chain d-f mixed-metal coordination polymer
      generated from an organometallic ligand.
AB  - A flexible organometallic ligand, 1,1'-ferrocenedicarboxylic acid, was
      incorporated in the self-assembly of a d-f mixed-metal coordination polymer
      featuring a 2-D interlinking zigzag-chain network and bearing two kinds of
      bridging conformations.

PMID- 12510315
TI  - Steric hindrance to the solvation of melamines and consequences for non-covalent
      synthesis.
AB  - Steric hindrance to solvation disfavors structures like 1 synanti in which the
      melamine exposes to the solvent faces, such as tBu-H, for whom binding to the
      ring nitrogen is hindered but not blocked; steric hindrance to solvation lowers
      the barriers to rotation in solvents which bind the triazine nitrogens, therefore
      these solvents display the fastest rates for assembling/disassembling processes.

PMID- 12510316
TI  - Highly efficient synthesis of [3]- and [5]-rotaxanes consisting of crown ether
      and a sec-ammonium salt.
AB  - [3]- and [5]-rotaxanes consisting of crown ether and ammonium salts were
      synthesized in high yields by a tributylphosphine-catalyzed end-capping method
      which provides a simple and practical means of obtaining higher-order rotaxanes.

PMID- 12510317
TI  - Novel synthesis of porous carbons with tunable pore size by surfactant-templated
      sol-gel process and carbonisation.
AB  - Surfactant-templated sol-gel polymerisation was explored to synthesize the
      resorcinol-formaldehyde (RF) gels without supercritical drying step, which were
      further carbonised to obtain porous carbons of a tunable pore size.

PMID- 12510318
TI  - Sulfonamides as novel terminators of cationic cyclisations.
AB  - Trifluoromethanesulfonic (triflic) acid is an excellent catalyst for inducing
      overall 5-endo cyclisation of homoallylic sulfonamides [e.g. 4] to give
      pyrrolidines [e.g. 5]. In competitive experiments, pyrrolidines or
      homopiperidines are formed in preference to piperidines, even when the latter
      would be obtained by trapping a tertiary carbocation. Cationic cascades
      terminated by a sulfonamide group are viable for the efficient formation of
      polycyclic systems.

PMID- 12510319
TI  - Fluorine takes a hike: remarkable room-temperature rearrangement of the C1 isomer
      of C60F36 into the C3 isomer via a 1,3-fluorine shift.
AB  - In a toluene/CDCl3 solution at room temperature, the C1 isomer of C60F36
      rearranges into the C3 isomer over a period of four days, as a result of a unique
      1,3-shift of fluorine; this rare example of addend migration across a fullerene
      cage surface is accelerated by air.

PMID- 12510320
TI  - A new heterogeneous catalyst for the oxidative carbonylation of phenol to
      diphenyl carbonate.
AB  - Using layered double hydroxides as a support, both the palladium catalyst and the
      cobalt co-catalyst are heterogenised and proven to form an acceptable catalytic
      system for the heterogeneous oxidative carbonylation of phenol to diphenyl
      carbonate (DPC).

PMID- 12510321
TI  - Motexafin gadolinium reacts with ascorbate to produce reactive oxygen species.
AB  - Motexafin gadolinium (MGd) oxidizes ascorbate, in neutral buffer and in cell
      culture, forming reactive oxygen species and a coordination polymer with oxalate.

PMID- 12510322
TI  - Coordination structure of various ligands in crosslinked PVA to silver ions for
      facilitated olefin transport.
AB  - The most effective ligand among -OH, -O- and -CHO for facilitated olefin
      transport by silver ions in room temperature crosslinked poly(vinyl alcohol)
      membrane has been evaluated.

PMID- 12510323
TI  - A dithienylethene-tethered beta-cyclodextrin dimer as a photoswitchable host.
AB  - The binding of TSPP by a dithienylethene-tethered beta-cyclodextrin dimer can be
      altered reversibly by irradiation with light.

PMID- 12510324
TI  - Mechanical stability enhancement by pore size and connectivity control in
      colloidal crystals by layer-by-layer growth of oxide.
AB  - Control of the pore size and connectivity of micro-sphere colloidal crystal
      lattices has been achieved by a layer-by-layer growth of silica using atmospheric
      pressure room temperature chemical vapour deposition of silica, a method which
      largely increases the mechanical stability of the lattice without disrupting its
      long range order.

PMID- 12510325
TI  - Low-temperature catalytic decomposition of N2O on platinum and bismuth-modified
      platinum: identification of active sites.
AB  - Classification of the active surface sites of platinum catalysts responsible for
      low temperature N2O decomposition, in terms of steps, kinks and terraces, has
      been achieved by controlled addition of bismuth to as-received platinum/graphite
      catalysts.

PMID- 12510326
TI  - Detonation chemistry of a CHNO explosive: catalytic assembling of carbon
      nanotubes at low pressure and temperature state.
AB  - The detonation of a CHNO explosive was used for the first time to synthesize
      carbon nanotubes effectively at low pressure and temperature by introducing a
      cobalt catalyst and/or paraffin into the detonation system.

PMID- 12510327
TI  - Photoassisted NO reduction with NH3 over TiO2 photocatalyst.
AB  - Photoassisted selective catalytic reduction of NO with ammonia (photo-SCR) at low
      temperature over irradiated TiO2 in a flow reactor was confirmed to proceed
      efficiently and the adsorbed ammonia reacted with NO under irradiation of TiO2.

PMID- 12510329
TI  - 'My own blood back...': a paediatric autologous blood donation programme.

PMID- 12510330
TI  - Therapeutic restraint of children: it must always be justified.

PMID- 12510331
TI  - Parental management of over-the-counter medicines.
AB  - Parental decision making on the use of over-the-counter (OTC) medicines in
      managing their child's illness was examined in this study. Twenty five parents
      were interviewed following completion of their purchase in community pharmacies.
      The most common purchase was Calpol. Parents were generally unaware of potential
      side effects of the medicines they purchased, although they said they used
      product information leaflets as a source of information. Advice-seeking decisions
      were influenced by the severity of symptoms and the experience of the parent.
      Sixteen parents thought the medicines were costly and although children are
      entitled to medicines free on GP prescription, the parents in this study had
      chosen to purchase a medicine for reasons such as convenience accessibility,
      choice and confusion as to their entitlements. Factors such as socio-economic
      status, number and age of children, parental age and working families contribute
      to the complexities of how often and which types of over-the-counter medicines
      are bought for children. The possibility of OTC medicine use must be remembered
      and explored by healthcare professionals when children present for treatment.

PMID- 12510332
TI  - Food challenges: a review and audit.

PMID- 12510333
TI  - Managing change through audit: post-operative pain in ambulatory care.

PMID- 12510334
TI  - Paediatric pharmacological principles: an update. Part 2. Pharmacokinetics:
      absorption and distribution.

PMID- 12510335
TI  - [Clinical indicators for day hospital and day surgery managed
      otorhinolaryngologic and cervicofacial diseases. Update 2002].

PMID- 12510336
TI  - [Balance disorders in the elderly].
AB  - In the elderly patient, instability is a syndrome in which a loss of balance,
      during ambulation or while standing, can give rise to falls, with consequent
      disability and morbidity. Maintaining the correct static and dynamic balance is
      known to be the result of the synergetic functioning of different systems. In old
      age, however, the efficiency of these mechanisms is impaired because of the
      physiological process of aging, which affects all of the organs and systems of
      the human body. Besides that, different concomitant causes such as cardiovascular
      and dysmetabolic pathologies, chronic pharmacological therapies etc. contribute
      to the aging of our organism. The object of this study was to evaluate 40
      subjects, 21 males and 19 females, aged between 70 and 86, who were referred to
      us with craniofacial trauma consequent to a fall. Upon hospitalization, all of
      the patients were asked to fill in a questionnaire evaluating the incidence of
      the vertigo symptom as a possible cause of the falls. All of the subjects
      underwent the following clinicoinstrumental examinations: standard audiometric
      evaluation, vestibular tests, neurological and ophthalmic examination. Careful
      appraisal of the results obtained enabled us to conclude that balance disorders
      in the elderly patient are due to the synergetic action of three factors: aging,
      concomitant diseases and environmental factors. In conclusion, we can affirm that
      balance disorders giving rise to a fall in the elderly are attributable to the
      concomitance of different factors that determine a clinical state of imbalance,
      defined by some Authors with the term "presbivertigo". It follows that a suitable
      diagnostic protocol must be employed, comprising a detailed medical,
      pharmacological and functional history, a study both of the environmental
      conditions in which the patient lives and the modalities according to which the
      traumatic event occurred. It is, last of all, indispensable that steps be taken
      to improve these environmental conditions, such as choosing flooring materials,
      light fixtures, stairs, bathroom furnishings and suitable footwear promoting
      proper foot placement and support on the ground.

PMID- 12510337
TI  - [Computerized modification of Fukuda test].
AB  - OBJECTIVES: To study a new method to apply to Fukuda test in order to overcome
      the interpretational difficulty associated with a subjective evaluation of the
      exam. MATERIALS AND METHODS: During the exam, the patient wears a specially
      designed headpiece, with a band at the back fitted with a sensor accommodating
      both a gyroscope and a bi-axial accelerometer. When asked to step in place, he
      does so in the Romberg position, eyes closed, successively rotating his head to
      the right and to the left. RESULTS: On analyzing the data obtained through the
      laterality variable (right/left oscillation) and time variable, it resulted that
      the difference between the averages referring to the laterality variable of right
      handed and left-handed subjects was statistically significant (P = 0.001), while
      the difference between the averages of the time variable was not. CONCLUSIONS: To
      be able to propose an evaluation of the clinical validity of the test, further
      research must be carried out on pathological subjects, thus verifying the
      applicability of the method to the full.

PMID- 12510338
TI  - [Lymph node metastases in paranasal sinus carcinoma: prognostic value and
      treatment].
AB  - The purpose of this report is to assess, on the basis of a sizeable study, the
      prognostic value of lymph node metastases in paranasal sinus carcinoma and, in
      particular, in squamous cell carcinoma of the maxillary sinus. We have reviewed
      the charts of 601 cases of paranasal sinus carcinoma between 1970 and 1999. All
      of the patients were treated surgically, alone or associated with chemotherapy
      and/or radiotherapy. The maxillary sinus tumors numbered 379 (153 squamous cell
      carcinomas, 15 undifferentiated carcinomas, 94 adenoid cystic carcinomas, 19
      adenocarcinomas, 98 mesenchymal tumors and rare forms) and the ethmoidal tumors
      were 222 (117 adenocarcinomas, 27 squamous cell carcinomas, 16 adenoid cystic
      carcinomas, 13 undifferentiated carcinomas, 49 other histological forms). Lymph
      node metastases in ethmoidal tumors were rare, with the exception of
      undifferentiated carcinoma (46.1%). The percentages of metastatic squamous cell
      carcinoma of the maxillary sinus upon presentation were: T2 15.5%, T3 7%, and T4
      4%. All these patients underwent lymph node excision. The metastases successive
      to treatment of the primary tumor were: T2 16.9%, T3 8.8%, and T4 12%. 75% of
      these late metastases occurred contemporaneously with a recurrence of T and only
      5 (25%) constituted the single reawakening of disease; four of these patients
      underwent neck surgery and were cured operatively. One had fixed, inoperable
      metastases. The NED survival rate at least two years after T therapy in patients
      free from metastases was 50.4%, against 25% in those with initial or distant
      metastases (T2 72.9% vs. 30.4%, T3 37.5% vs. 22.2%, and T4 28.6% vs. 0%). In
      conclusion, squamous cell carcinomas of the maxillary sinus which have extended
      to the oral cavity (T2) show greater lymph node propagation than those of the
      superoposterior portion (T3-T4). The presence or successive appearance of lymph
      node metastases indicates elevated malignancy of the tumor, with a very negative
      prognosis. N, however, is rarely the cause of death for these patients.
      Prophylactic lymph node excision in N0 patients is therefore not indicated.

PMID- 12510339
TI  - [Surgical features on intraoral approach for the management of isolated zygomatic
      arch fractures].
AB  - The Authors report on their experience of 18 patients with isolated fractures of
      the zygomatic arch who were treated via intraoral approach. The procedures were
      performed between the 2nd and 8th post-trauma day and the results obtained were
      evaluated via post-operative CT scan and periodic follow-up visits for six
      months. In describing the surgical technique, the Authors recommend that the
      fracture be reduced with the patient's mouth open, in order to overcome the
      anatomical obstacle constituted by the coronoid process of the mandible and
      avoid, as far as possible, external approaches and osteosynthesis with screws or
      miniplates, which often give rise to unaesthetic results and localized pain. In
      conclusion, this approach is seen to be the method of choice in the treatment of
      isolated zygomatic arch fractures in that it is simple, effective and
      substantially free from complications.

PMID- 12510340
TI  - [Preliminary results in the use of polydimethylsiloxane textured elastomers
      (Bioplastique) in the treatment of leakage around tracheoesophageal voice
      prosthesis].
AB  - Leakage around the prosthesis is one of the worst problems afflicting patients
      fitted with tracheoesophageal (TE) voice prosthesis. Removing the prosthesis for
      a few days can reduce the size of the fistula, or the leakage may be eliminated
      simply by replacing the prosthesis. In cases that are refractory to such
      treatment, the perifistular injection of different types of autologous,
      heterologous or alloplastic substances has been proposed. A new kind of silicone,
      previously available abroad, has recently appeared on the Italian market as well;
      constituted by polydimethylsiloxane textured elastomers (Bioplastique) for soft
      tissue implants, it appears to guarantee excellent standards of long-term safety
      and stability. Three patients fitted with Provox2 tracheoesophageal voice
      protheses who had been experiencing leakage for about 4 months underwent
      Bioplastique implant procedures. The correction of the fistula size was easy to
      accomplish and well tolerated by the patients. There was no sign of inflammation,
      formation of granulomas or other pathological modifications, and the size of the
      fistula, together with its fluid-tightness, remained stable in time. From our
      point of view, the Bioplastique implant appears to provide valid and effective
      treatment of gaping TE fistulas.

PMID- 12510341
TI  - [Selective parathyroidectomy with unilateral cervical exploration for primary
      hyperparathyroidism].
AB  - Primary hyperparathyroidism (pHPT), is caused in over 90% of the cases by a
      single parathyroid adenoma. Preoperative diagnostic imaging techniques, in
      particular dual phase scintigraphy with SestaMIBI/TC99 and high frequency probe
      ecography, are able to pinpoint it 90% of the time. These are the two
      cornerstones of modern pHPT surgery, which has witnessed the passage from
      cervical exploration of all the most common parathyroid glandular sites to a more
      carefully targeted, restricted approach in the side of the neck where the adenoma
      is suspected to be. This is how selective parathyroidectomy with unilateral
      cervical exploration and, recently, mini-invasive parathyroidectomy, came into
      being. Between 1996 and 2001, in the Otolaryngology Department of S. Maria della
      Misericordia Hospital in Udine, 39 patients affected by pHPT, half of whom (49%)
      were asymptomatic, underwent selective parathyroidectomy with unilateral cervical
      exploration. The object of this paper was to evaluate the efficacy of this
      surgical technique by comparing the pre- and post-operative calcaemia and
      parathormone levels. The normalization of these parameters, and particularly of
      the latter, was considered indicative of successful treatment. All the
      postoperative calcaemia levels were normal, while elevated parathormone levels
      persisted in only 2 cases (5%). Our statistics showed a 95% efficacy for
      selective parathyroidectomy, a result that is comparable to the percentages
      described in the literature. There were, furthermore, no significant peri- or
      postoperative complications in any of the cases. These observations, together
      with the brief operating times required for the procedure (20-25 minutes on
      average) and the low cost of the material employed, enable us to conclude that
      selective parathyroidectomy with unilateral cervical exploration continues to
      hold its own as a valid option in the present scenario of surgical pHPT
      treatment, also in consideration of the fact that it does not present the rigid
      inclusion criteria characteristics of mini-invasive techniques.

PMID- 12510342
TI  - [Differential diagnosis in fibro-osseous lesions of facial bones: report of a
      case of ossifying fibroma and review of literature].
AB  - Ossifying fibroma is a relatively rare, benign neoplasm of non-odontogenic
      origin, affecting the facial bones, and prevalently localized in the mandible,
      but which can also appear in the maxilla, paranasal sinuses and peripheral bones.
      Its growth is generally very slow and it is usually asymptomatic, for which it
      often manages to reach a considerable size. An incidental diagnosis during
      orthopantography, on the other hand, is not infrequent. The diagnosis, which is
      fundamentally made by utilizing conventional x-rays and CT and NMR scans, may
      present several controversial aspects and is not to be disjointed from the
      clinical and anatomopathological aspects, for which close interdisciplinary
      collaboration is required in many cases. In effecting a differential diagnosis,
      the possibility of inflammatory lesions, other fibrous-osseous lesions (in
      particular, fibrous dysplasia) and benign or malignant neoplasms must be taken
      into consideration. The present work presents a case of ossifying fibroma of the
      maxilla that is emblematic in its clinical, radiological and histopathological
      aspects. It also discusses problems connected with classification and
      differential diagnosis, in particular with respect to fibrous dysplasia, which
      are important in determining the proper therapeutic approach.

PMID- 12510343
TI  - Plexus r+d fuses imagination and intellectual rigor with worldly, practical
      optimism.

PMID- 12510344
TI  - Sahel al-Hiyari sculpts space with strong geometry and modulated light.

PMID- 12510345
TI  - There is no north arrow in outer space.

PMID- 12510346
TI  - Vinyl by design: creating interior spaces that stand the test of time.
AB  - Managing design liability, avoiding risk and providing successful buildings are
      founded upon a conscious awareness of many important details. A key component of
      a designer's professionalism is understanding potential problems before they
      occur and proactively specifying the solutions to them. Familiarity with the
      inherent characteristics of any building material, along with the performance
      capabilities of specifiable products made with that material, aids in this
      process. Documenting the selection of a product in the project specifications
      should take this understanding into account. Knowing the important role of proper
      product installation--and, where necessary, calling upon the expertise of product
      manufacturers--should not be underestimated. Each part of the process has a major
      impact on whether the interior spaces delivered to a building owner provide
      lasting gratification, value, user satisfaction and recognition of the design
      professional's strategic importance to the project's overall success.

PMID- 12510347
TI  - [Etiology of rheumatoid arthritis in an animal model].

PMID- 12510348
TI  - [Novel autoantibodies and their target antigens in rheumatoid arthritis].
AB  - Recently identified autoantibodies in rheumatoid arthritis are targeting
      autoantigen molecules, such as calpastatin, a novel form of soluble gp130, and
      follistatin-related protein, that appear to play a role in protecting effects in
      joint inflammation. These autoantibodies inhibit the function of target molecules
      and may be involved in the pathogenic mechanisms by upregulating inflammation and
      joint destruction. Another autoantibody targets filaggrin, a citullurinated
      protein distributed in keratinated epithelia. Although the pathogenic effect of
      anti-filaggrin antibody is not elucidated, this autoantibody has a potentiality
      of a new diagnostic marker of RA because of its high sensitivity and specificity.

PMID- 12510349
TI  - [The molecular genetics of rheumatoid arthritis disease gene].
AB  - Rheumatoid arthritis(RA) is a chronic polyarthritis of unknown etiology affecting
      approximately 1% of the population worldwide. Previous studies have shown that
      the ratio of the risk for siblings of patients with the disease versus the
      prevalence of that disease in the general population (lambda s) is much greater
      in RA, suggesting that genetic factors may be involved in familial clustering.
      Using microsatellite marker analysis and sib-pair linkage study, we have
      identified three chromosome regions D1S214/253, D8S556 and DXS1232/984 as
      candidate loci for RA disease genes. In this article, we review the molecular
      genetic findings on the RA disease genes located respectively at each of the
      above chromosome regions. We show that the death receptor 3(DR3) gene, a Fas
      family member, containing nucleotide polymorphism is the candidate disease gene
      located at D1S214/253. We also identify the mutant forms of angiopoietin-1(Ang-1)
      and Dbl proto-oncogenes respectively as the candidate genes located at D8S556 and
      DXS1232/984. We surmise that these mutations are responsible for the impairment
      of apoptosis induction, angiogenesis and leukocyte function in the patients,
      which may predispose to autoimmunity.

PMID- 12510350
TI  - [Predictive factors of prognosis in rheumatoid arthritis].
AB  - Rheumatoid arthritis leads the patients to severe physical disability and the
      mortality is significantly worse than general population. To predict the
      prognosis at first visit in hospital is difficult but there are several factors
      influence on the prognosis; disease activity and it's duration, high titer of
      rheumatoid factor, male and vasculitis. The most important factor is disease
      activity and it's duration. Recent advance of the treatment of RA improve the
      prognosis of either disability or mortality. Adverse effects of drugs for RA may
      threaten the life but their use leads statistically significant improvement of
      mortality.

PMID- 12510351
TI  - [Gene therapy for rheumatoid arthritis].
AB  - Investigation of the pathogenesis of rheumatoid arthritis has led us to discover
      new candidate molecules as targets in RA therapeutic strategies. Gene therapy
      offers one of the best tools to deliver of such therapeutic molecules into the
      affected joints. In the past, many gene therapy trials preferred viral delivery
      methods to non-viral methods because of the difference in gene transfer
      efficiency. However, viral methods have many unresolved problems mainly related
      to safety. One example is immunogenicity of adenovirus vector. Efforts have been
      made to improve viral vectors for clinical application.

PMID- 12510352
TI  - [Cross-talk between immune and skeletal systems].
AB  - Bone destruction in rheumatoid arthritis is characterized as 'the defective
      control of bone metabolism by the immune system'. During the course of our study
      to investigate the mechanism of arthritic bone destruction, we have explored a
      new field called' osteo-immunology'. Here we summarize the regulation of the bone
      metabolism by signalling cross-talk between RANKL and IFNs, focusing on the T
      cell-mediated regulation of osteoclastogenesis by IFN-gamma. The better
      understanding of the interactions between bone and immune cells will provide
      further insights into the both fields.

PMID- 12510353
TI  - [Clinical evaluation of filtration leukocytapheresis(LCAP) in rheumatoid
      arthritis(RA)].
AB  - Filtration Leukocytapheresis(LCAP) is an alternative to thoracic duct drainage
      and LCAP using a centrifuge method with the advantages that it can be performed
      easily and inexpensively. Clinical trials revealed that LCAP is a safe and
      effective therapy for patients with drug-resistant rheumatoid arthritis(RA).
      Assessment of RA before and after LCAP showed a substantial and rapid improvement
      in tender joints counts, swollen joint counts, and patient's and physician's
      assessments. Careful analysis indicated that 64-80% of patients with RA showed >
      or = 20% improvement following LCAP therapy. Furthermore, we investigated the
      clinical evaluation of LCAP for RA over the 3 year-study period. Possible
      therapeutic mechanisms of LCAP on RA are summarized.

PMID- 12510354
TI  - [Cell transplantation therapy for the treatment of articular cartilage defect].
AB  - Articular cartilage destruction is a major problem in rheumatoid arthritis
      patients. However, there is no treatment that is widely accepted to
      regeneratively repair the lesion. When the joint cartilage is destructed
      progressively and activity of daily life is worsened, joint arthroplasty is the
      most common treatment to relieve joint pain though it has limited survivorship
      and sometimes severe complications. Recently in order to repair cartilage defect,
      new method with cell transplantation; autologous cultured chondrocyte
      transplantation has been put into clinical practice. And we also have reported
      autologous cultured-expanded bone marrow mesenchymal cell transplantation. These
      methods have possibility to repair cartilage defect with good quality
      histologically, biochemically and biomechanically.

PMID- 12510355
TI  - [New strategies for BMT].
AB  - Using various autoimmune-prone mice, we have previously shown that conventional
      allo BMT can be used to treat a range of autoimmune diseases. These findings have
      recently been confirmed even in humans. However, in humans, the success rate of
      BMT across major histocompatibility complex(MHC) barriers is lowered by graft
      versus-host disease(GvHD), graft rejection, and incomplete T-cell recovery. We
      have just established a new BMT method in which bone marrow cells(BMCs) are
      directly injected into the intra-bone marrow(IBM-BMT). We here show that 'IBM
      BMT' is the best strategy for allo BMT and also organ allografts to induce
      persistent tolerance.

PMID- 12510356
TI  - [Recent progress of radiology in rheumatoid arthritis: a role of magnetic
      resonance imaging].
AB  - Since MR imaging directly visualizes all articular components with excellent
      contrast resolution, it allows the joint to be viewed as a whole organ. An
      increasing aggressive therapeutic strategy has attracted growing attention to the
      potentials of MR imaging in the diagnosis, prognostication, and outcome measure
      of RA. The introduction of MR imaging into the diagnostic criteria for early RA
      contributes to more accurate diagnosis in patients suspected of having RA and
      thus allow an earlier decision to start proper medication. Quantification of
      inflammatory synovitis by MR imaging can assess treatment outcome in fewer
      subjects than with traditional measures. We believe MR imaging can be cost
      effectively incorporated in the treatment trial.

PMID- 12510357
TI  - [Usefulness of serum matrix metalloproteinase-3(MMP-3) level in the diagnosis of
      rheumatoid arthritis].
AB  - Matrix metalloproteinase-3 is abundantly expressed in active rheumatoid synovium,
      and serum level of MMP-3 is a useful marker not only for the diagnosis of
      rheumatoid arthritis but also for the evaluation of prognosis in the joint
      destruction. It should be noted, however, that serum MMP-3 may be increased in
      other inflammatory arthritis, thus its specificity for the diagnosis of early RA
      may not be high enough. Recent reports indicated that methotrexate or anti-TNF
      alpha therapy effectively suppressed the serum MMP-3 level during the course of
      the treatment, whereas corticosteroid didn't. Thus, suppression of serum MMP-3
      could explain the discrepancy in the inhibition of bony destruction in RA
      patients by the therapeutic strategy.

PMID- 12510358
TI  - [Methotrexate for the treatment of rheumatoid arthritis in Japan--much more still
      remains to be resolved].
AB  - Methotrexate(MTX) is an antifolic agent and has been widely used for RA since
      early 1980s. Since 1999 when MTX was approved as an antirheumatic drug in Japan,
      patients taking MTX has been increasing and about sixty thousands patients are
      estimated to be taking MTX for the treatment of RA. The highest efficacy relative
      to toxicity of MTX is supported by the highest retention rate among current
      DMARDs. Therefore, most of rheumatologist places MTX as a golden standard of
      DMARD. Recent RCT data in European and North American countries showed that ACR
      20 and 50 responses are ranging from 60 to 70% and from 40 to 50%, respectively.
      In these clinical trials, MTX was usually started at a dose of 7.5 mg weekly and
      then increased to 15-20 mg/week if the disease activity was still present since
      the clinical effect of MTX is related to the dose in the range 5 to 20 mg weekly.
      However, an upper limit of clinical dose of MTX (Rheumatrex) for RA is set to 8
      mg weekly and this is a major problem because the majority of patients with
      active RA need higher doses for the suppression of arthritis. This matter needs
      an immediate solution. If MTX would be used aggressively for the early
      suppression of RA, informed consent regarding MTX dose and side effects including
      their earlier signs should be obtained, especially when patients are taking more
      than 8 mg weekly.

PMID- 12510359
TI  - [Pharmacogenetics of disease modifying anti-rheumatic drugs].
AB  - There are large differences in the effectiveness of disease modifying anti
      rheumatic drugs(DMARD) from one person to the next. Adverse drug reactions caused
      by DMARD can also occur to some patients, but do not occur to others. One
      possible cause of the differences in the effectiveness and adverse drug reactions
      is genetic variation in how individuals metabolize drugs. The Human Genome
      Project heralds new opportunities for using information about genetic variation
      to predict responses to drug therapies, called pharmacogenetics. Based on
      pharmacogenetics, tailor-made drug therapy is going to be realized. Our recent
      studies revealed the relationship between genetic polymorphisms of drug
      metabolizing enzymes and the efficacy of methotrexate or sulfasalazine in
      patients with rheumatoid arthritis, suggesting pharmacogenetics is applicable to
      the treatment of rheumatoid arthritis.

PMID- 12510360
TI  - [Clinical implication of cyclosporin for rheumatoid arthritis].
AB  - Cyclosporin is a non-cytotoxic immunomodulating drug which inhibits NF-AT
      dependent IL-2 transcription in lymphocytes. Cyclosporin is, therefore,
      beneficial as a monotherapy or as a combined therapy with methotrexate for
      refractory rheumatoid arthritis (RA). We also document that cyclosporin recovers
      the low concentration of intracellular multidrugs in lymphocytes by competitively
      binding to P-glycoprotein, a product of multidrug resistance gene-1, in vitro.
      Thus, cyclosporin could be used for the reversal of multidrug resistance,
      experienced in patients with longterm treated RA.

PMID- 12510361
TI  - [Combination therapy of disease-modifying antirheumatic drugs(DMARDs) in
      rheumatoid arthritis].
AB  - The early suppression of disease activity during the first 2 years in rheumatoid
      arthritis (RA) has been reported to be exclusively important to prevent joint
      destruction and functional decline. Since single disease-modifying antirheumatic
      drugs(DMARDs) therapy is still disappointing, many rheumatologists today
      advocated a more aggressive approach using combinations of classic DMARDs. Many
      clinical trials on combination therapy have been reported and most studies of
      combination therapy focused on the efficacy of a treatment strategy. Therefore,
      the possible synergistic action of combination of drugs has not been
      demonstrated. Among combination of therapy of classical DMARDs, only few trials
      demonstrated the efficacy of combination therapy. The incidence of adverse
      effects among 341 RA patients was investigated by our department. The incidence
      of adverse effect in combination therapy revealed 36.4% which was not
      statistically different from that in monotherapy(33.6%, p = 0.41). The recent
      studies on combination therapy on classical DMARDs are not encouraging, however,
      the combination therapy for patients with early RA, drugs utilizing
      immunosuppressant, biologics and other newly developed drugs will still have a
      chance to expect a potent efficacy for RA.

PMID- 12510362
TI  - [Efficacy of leflunomide].
AB  - Leflunomide(Arava) is a novel immunomodulatory drug, the primary action of which
      is inhibition of de-novo pyrimidine synthesis by selective inhibition of dihydro
      orotate dehydrogenase. It has been shown that leflunomide is effective in
      treating active rheumatoid arthritis(RA) in a placebo-controlled phase II study.
      Subsequent multinational, randomized, controlled phase III clinical trials
      demonstrated that leflunomide is as effective and safe as methotrexate and
      sulfasalazine in treatment of RA. Frequently reported adverse effects included
      diarrhea, nausea and vomiting, skin rash, reversible alopecia, and transient
      lever enzyme elevations. However, accumulating concerns about its toxic effects,
      especially hepatotoxicity, have been raised recently. In addition,
      rheumatologists should be aware that leflunomide has a much longer half life than
      any other disease modifying antirheumatic drug.

PMID- 12510363
TI  - [Systemic corticosteroids in rheumatoid arthritis: to use or not to use?].
AB  - Systemic corticosteroids(steroids) were initially introduced after the dramatic
      efficacy in individual patients with rheumatoid arthritis(RA). Since the outcome
      of steroid therapy in RA turned to be awesome, steroids had been put at the apex
      of the therapeutic pyramid for a long time. However, most rheumatologists have
      subscribed steroids for the treatment of early active RA because they can provide
      rapid and significant clinical response. Moreover, recent several studies have
      shown that low dose(5 to 10 mg/day) of prednisolone retard joint destruction in a
      few years. However, the demonstrated negatives(opportunistic infections,
      osteoporosis, metabolic disorders, atherosclerotic vascular events etc.) of
      steroids may outweigh these advantages in the longterm clinical course of RA.

PMID- 12510364
TI  - [Recent development of selective cyclooxygenase-2 inhibitors].
AB  - Nonsteroidal anti-inflammatory drugs(NSAIDs) are clinically effective against the
      inflammatory symptoms of rheumatoid arthritis. Recent attention has been focused
      on selective cyclooxygenase(COX)-2 inhibitors, a type of NSAID that inhibits a
      subtype of COX. Because of the different actions of COX-1 and COX-2, selective
      COX-2 inhibitors were expected to reduce adverse reactions such as
      gastrointestinal disorders. Various clinical studies have confirmed that the
      efficacy of COX-2 inhibitors for RA is similar to that of conventional NSAIDs,
      but they cause fewer severe gastrointestinal disorders. The incidence of
      complications related to renal dysfunction, such as edema and hypertension, is
      not different. Patients using selective COX-2 inhibitors have recently been
      reported to show an increase in thrombotic complications such as myocardial
      infarction. Therefore, more data on adverse events should be collected in the
      future from large-scale clinical studies to further clarify the actual value of
      selective COX-2 inhibitors.

PMID- 12510365
TI  - [Infliximab in the treatment of rheumatoid arthritis].
AB  - Infliximab is a chimeric monoclonal antibody capable of neutralizing human TNF
      alpha. A number of clinical trials for the treatment of rheumatoid arthritis(RA)
      with infliximab indicated that TNF alpha blockade was effective and well
      tolerated with the excellent results occurring at 3 and 10 mg/kg in combination
      with methotrexate. Treatment of RA patients with the combination of infliximab
      and methotrexate also prevented radiographic evidence of progression of joint
      damage. If the clinical efficacy is sustained and the safety is confirmed over
      the long term, infliximab may become an essential agent of choice for the
      treatment of RA.

PMID- 12510366
TI  - [Adalimumab].
AB  - Recently, the anti-tumor necrosis factor(TNF)-alpha treatments for RA are
      successful in alleviating the discomforts associated with swollen, painful
      joints. Adalimumab(D2E7) is the first fully human anti-TNF-alpha monoclonal
      antibody(IgG1). Therefore, it has low immunogenicity and possibly greater
      therapeutic potential compared with other anti-TNF-alpha antibodies. This is
      administered subcutaneously at a dose of 1 mg/kg biweekly. The combined therapy
      with methotrexate(MTX) is efficacious to the patients who receive MTX alone and
      are insufficient to control symptoms of RA. The therapeutic effects become
      evident within 24 hours to one week after administration and reached maximum
      effect after one to two weeks. In adalimumab recipient, radiographic progression
      is also controlled and serum levels of matrix metalloproteinase-1(MMP-1) and MMP
      3 decrease. For patients with RA, the treatment of adalimumab will set a new
      standard for symptom control and joint protection.

PMID- 12510367
TI  - [Etanercept].
AB  - Etanercept is a protein comprised of the extracellular domains of two TNF
      receptors attached to a Fc portion of an IgG. Etanercept was approved for not
      only reducing signs and symptoms but inhibiting of structural damage in patients
      with active RA who had an inadequate response to one or more DMARDs. Moreover,
      combination therapy with methotrexate will be attractive for severely active
      patients. The proportion of patients who have discontinued therapy due to adverse
      events is approximately 4%. Etanercept has not raised the risk for serious
      infections(0.04/patient-year) as well as malignancies. There are sporadic case
      reports of aplastic anemia, demyelination, lupus-like conditions, which are not
      significant so far. Etanercept may contribute rheumatologists to manage patients
      with RA.

PMID- 12510368
TI  - [Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin
      1 receptor antagonist].
AB  - Anakinra, a recombinant human interleukin-1 receptor antagonist offers a new
      potent treatment for rheumatoid arthritis(RA). It is administered as a daily
      single subcutaneous injection. Recent randomized, double-blind, placebo
      controlled trials revealed that anakinra significantly reduces the signs and
      symptoms of RA, reduces joint destruction, and is safe and tolerated. It was also
      revealed that anakinra is more potent when used in combination with methotrexate.

PMID- 12510369
TI  - [A humanized anti-IL-6 receptor antibody(MRA) in RA therapy].
AB  - Hyperproduction of Interleukin-6(IL-6) is observed in the rheumatoid
      arthritis(RA) patients and serum level of IL-6 is closely related to disease
      activity. IL-6 is a pleiotropic cytokine and its hyperfunctions explain most of
      the clinical symptoms in RA. Since MRA is humanized antibody from a mouse anti
      human IL-6 receptor antibody, MRA can be administered repeatedly because of its
      low antigenesity to human. MRA inhibits IL-6 function by the blocking IL-6
      binding to IL-6 receptor, resulting the prevention of development on collagen
      inducing arthritis(CIA) in cynomolgus monkeys whose IL-6R is cross-reacted with
      MRA. These evidence suggest that MRA has anti-arthritic effects. Clinical trials
      of MRA for RA patients have already started, and MRA therapy is effective as well
      as anti-TNF alpha and anti-IL-1 therapies.

PMID- 12510370
TI  - [The rheumatoid vasculitis and malignant rheumatoid arthritis(MRA)].
AB  - The inflammatory process characteristic of rheumatoid arthritis is typically
      targeted to the synovial membrane. In a subset of patients, rheumatoid disease is
      complicated by an inflammatory destruction of blood vessels, rheumatoid
      vasculitis. Rheumatoid vasculitis has been understood to be the result of severe
      disease extending beyond the joint, possibly caused by immune complex deposition.
      However, in Japan malignant rheumatoid arthritis(MRA) is designated as rheumatoid
      arthritis with vasculitis. Rheumatoid arthritis patients can be separated into
      two groups: individuals with synovial disease and individuals with synovial plus
      extra-articular disease, MRA. The model is supported by immunogenetic analysis
      describing an accumulation of vasculitis patients with rheumatoid arthritis among
      HLA-DRB10401 homozygotes. Therapy depends upon the clinical manifestation of
      rheumatoid vasculitis. Then, MRA is usually treated with steroid, and steroid
      pulse therapy and immunosuppressants are useful for severe MRA.

PMID- 12510371
TI  - [Secondary amyloidosis in patients with rheumatoid arthritis(RA)].
AB  - The amyloidoses are a group of protein deposition diseases in which amyloid
      proteins composed of insoluble fibrils are deposited in various organs. Most
      cases of the secondary amyloidosis(AA amyloidosis) in which amyloid A(AA) protein
      is deposited followed by uncontrolled, long term RA(duration 7 to 10 years). It
      has been revealed that the multi-organ dysfunction associated with AA amyloidosis
      causes the deterioration of RA prognosis. Since the mechanism of amyloid protein
      deposition is still unknown, the diagnosis of AA amyloidosis is difficult and
      there is no fundamental therapy for it; there are only supportive therapies for
      the malfunction of involved organs.

PMID- 12510372
TI  - [Lung involvements of RA, diagnosis and treatment].
AB  - Various pleuro-pulmonary abnormalities and conditions are known to complicate
      rheumatoid arthritis. Some of them are asymptomatic, tend to ameliorate
      spontaneously(ex. pleuritis and rheumatoid nodule), others may cause serious
      conditions and often fatal(ex. interstitial pneumonia and constrictive
      bronchiolitis). Furthermore therapy-related lung complications and opportunistic
      infections may develop in RA patients. Clinicians must differentiate these
      conditions, using serological, physiologic, bacteriological, radiographic, and if
      necessary, invasive techniques including bronchoscopy and video-assisted
      thoracoscopic surgery. Therapy may vary according to the nature of these
      conditions. Appropriate anti-microbial agent must be given for infectious
      diseases. On the other hands immuno-suppressive therapy should be applied for
      interstitial pneumonia if the disease progress rapidly and threaten life. Anti-RA
      drugs should be withdrawn in case of drug-induced lung injury.

PMID- 12510373
TI  - [Timing of surgical treatment in the patients with rheumatoid arthritis].
AB  - Rheumatoid arthritis is a systemic and consumptive disease of unknown cause, and
      there is no specific therapy for the disease. Surgical treatment in one of the
      total management that can effectively relieve pain and improve function in
      patients with rheumatoid arthritis include synovectomy, joint arthroplasty,
      resection arthroplasty, osteotomy, fusion, and soft tissue arthroplasty. Four
      cases with rheumatoid arthritis treated with surgical procedures were
      demonstrated, and discussed on the timing of operative treatment in the patients.

PMID- 12510374
TI  - [Chronic rheumatoid arthritis and the long-term care insurance system in Japan].
AB  - The long-term care insurance system in Japan is the social support system for the
      elderly, mainly aged 65 or over, requiring long-term care and provides necessary
      welfare services and health and medical care services of the user's choice in a
      comprehensive and unified manner. On the other hand, chronic rheumatoid arthritis
      often causes various disturbance and needs of long-term care for daily life in
      accordance with the progression of the disease. This system shall be provided to
      patients aged 40 or over with chronic rheumatoid arthritis, after screened by the
      long-term care approval board. Combination with both services not covered by the
      long-term care insurance and the Government Action Plan for Persons with
      Disabilities, users shall be provided comprehensive and planned services.

PMID- 12510375
TI  - [Gas biology: how do the gases conduct protein function in vivo?].

PMID- 12510376
TI  - [Atomic force microscope: application to life science].

PMID- 12510377
TI  - [Post-transcriptional regulation of gene expression by GSPT family members].

PMID- 12510378
TI  - [Structure and function of a novel PP-1 specific inhibitor, tautomycetin].

PMID- 12510379
TI  - [Molecular mechanism of pexophagy].

PMID- 12510380
TI  - [A novel adaptor protein family regulating cytoskeletal organization and signal
      transduction--Vinexin, CAP/ponsin, ArgBP2].

PMID- 12510381
TI  - [Regulation of genome replication].

PMID- 12510382
TI  - [Development of rheumatoid arthritis and abnormal IgG galactosylation].

PMID- 12510383
TI  - [Development of novel synthetic organic reactions: synthesis of antitumor natural
      products and leading compounds for new pharmaceuticals].
AB  - Biologically active natural products with unique, highly complex molecular
      skeletons have been used as leading compounds for raw materials of new drugs. Due
      to the limitations of natural supply, highly efficient, large-scale syntheses and
      molecular design have been sought in drug discovery. For this purpose, we have
      focused on a synthetic strategy effective in developing novel reactions and
      reagents and found several useful regio- and stereospecific reactions,
      contributing to the synthesis of otherwise unattainable target molecules. The
      application of these reactions for the total synthesis of three types of potent
      cytotoxic natural products for the first time is described in this paper. The
      basic concept is first described. Then the total synthesis of anthracyclines,
      fredericamycin A, and discorhabdins is reported. Novel reactions using
      hypervalent iodine reagents under environmentally benign conditions are also
      described. The future prospects for this method are discussed.

PMID- 12510384
TI  - [Biopharmaceutical studies on molecular mechanisms of membrane transport].
AB  - By incorporating the transporter-mediated or receptor-mediated transport process
      in physiologically based pharmacokinetic models, we succeeded in the quantitative
      prediction of plasma and tissue concentrations of beta-lactam antibiotics,
      insulin, pentazocine, quinolone antibacterial agents, and inaperizone and
      digoxin. The author's research on transporter-mediated pharmacokinetics focuses
      on the molecular and functional characteristics of drug transporters such as
      oligopeptide transporter, monocarboxylic acid transporter, anion antiporter,
      organic anion transporters, organic cation/carnitine transporters (OCTNs), and
      the ATP-binding cassette transporters P-glycoprotein and MRP2. We have
      successfully demonstrated that these transporters play important roles in the
      influxes and/or effluxes of drugs in intestinal and renal epithelial cells,
      hepatocytes, and brain capillary endothelial cells that form the blood-brain
      barrier. In the systemic carnitine deficiency (SCD) phenotype mouse model,
      juvenile visceral steatosis (jvs) mouse, a mutation in the OCTN2 gene was found.
      Furthermore, several types of mutation in human SCD patients were found,
      demonstrating that OCTN2 is a physiologically important carnitine transporter.
      Interestingly, OCTNs transport carnitine in a sodium-dependent manner and various
      cationic drugs transport it in a sodium-independent manner. OCTNs are thought to
      be multifunctional transporters for the uptake of carnitine into tissue cells and
      for the elimination of intracellular organic cationic drugs.

PMID- 12510385
TI  - [Development of new chronopharmacotherapies based on biological rhythm].
AB  - The mammalian circadian pacemaker resides in the paired suprachiasmatic nuclei
      (SCN). Clock genes are the genes that control the circadian rhythms of physiology
      and behavior. The effectiveness and toxicity of many drugs vary depending on
      dosing time associated with 24-h rhythms of biochemical, physiological, and
      behavioral processes under the control of the circadian clock. However, many
      drugs are still administered without regard to the time of day. Identification of
      a rhythmic marker for selecting dosing time will lead to improved progress and
      diffusion of chronopharmacotherapy. The monitoring of rhythmic markers may be
      useful in choosing the most appropriate time of day for administration of drugs
      and may increase their therapeutic effects and/or reduce their side effects. On
      the other hand, several drugs can cause alterations in 24-h rhythms, leading to
      illness and altered homeostatic regulation. Here, we show the disruptive effect
      of interferon on the rhythm of locomotor activity, body temperature, and clock
      gene mRNA expression in the periphery and SCN. The alteration of the clock
      function, a new concept of adverse effects, can be overcome by devising a dosing
      schedule that minimizes adverse drug effects on clock function. Furthermore, to
      produce new rhythmicity by manipulating the conditions of living organs using
      rhythmic administration of altered feeding schedules or several drugs appears to
      lead to the new concept of chronopharmacotherapy. One approach to increasing the
      efficiency of pharmacotherapy is administering drugs at times during which they
      are best effective and/or tolerated.

PMID- 12510386
TI  - [Creation of functional recognition molecules for chemical modification of gene
      expression].
AB  - Artificial molecules that exhibit specific recognition of duplex DNA have
      attracted great interest because of their potential application in the
      manipulation of gene expression. Specific chemical reactions to the target base
      within the predetermined site would secure selective inhibition at either
      translation or transcription reactions. A more interesting application would be
      to alter the reacted base structure to induce a point mutation. In our study, we
      have focused our efforts on: 1) development of new cross-linking molecules with
      high efficiency as well as high selectivity; 2) establishment of a new molecular
      basis for the formation of nonnatural triplexes; and 3) synthetic approaches to
      the new minor groove binders. This paper summarizes our recent results using two
      new functional molecules: 2-amino-6-vinylpurine derivatives as new cross-linking
      agents; and W-shaped nucleic acid analogues as new recognition molecules for the
      formation of nonnatural-type triplexes.

PMID- 12510387
TI  - [Supramolecular chemistry of multinuclear zinc(II) complexes in aqueous
      solution].
AB  - We report novel supramolecular polyhedrons formed by three-dimensional self
      assembly of multinuclear zinc(II)-12-membered tetraamine (= cyclen = 1,4,7,10
      tetraazacyclododecane) complexes with potentially multidentate ligands such as
      cyanuric acid (CA) and trithiocyanuric acid (TCA) in aqueous solution. Two new
      supermolecular frameworks were isolated by self-assembly of a tris (Zn(2+)
      cyclen) (Zn3L1) with di-(CA2-) or tri-deprotonated cyanuric acid (CA3-) in
      aqueous solution. One was a very stable 2:3 complex of Zn3L1 and CA2- formed
      above pH6, which was stable in aqueous solution at neutral pH. The second was an
      unexpected supramolecular complex formed by 4:4 self-assembly of Zn3L1 and CA3-,
      which was isolated by allowing a 1:1 mixture of Zn3L1 and CA to stand in aqueous
      solution at pH 11.5. X-ray crystal analysis showed a highly symmetric 4:4
      assembly complex with a cuboctahedral exterior and an inner hollow, which was
      schematically represented as a truncated tetrahedron formed by binding four
      equilateral triangles and four scalene hexagons with each other through CA(3-)
      Zn2+ bonds. The 4:4 complex was found to be stable only in solid form or in DMSO
      solution and tends to revert to the 2:3 complex in the presence of H2O. This
      problem has been overcome by replacing CA with TCA, of which the thioimide
      functions possess lower pKa values than those of CA. TCA acted as a tridentate
      donor for three Zn3L1 at neutral pH to yield a similar type of 4:4 self
      assembling supercomplex, in which the deprotonated TCA3- in an aromatic 1,3,5
      triazine binds to Zn3L1 through Zn(2+)-S- (exocyclic) coordination bonds, and
      thus the 4:4 assembly is a chiral twisted cuboctahedron. More interestingly, this
      supramolecular capsule was found to be stabilized by encapsulation of various
      size-matched and hydrophobic guest molecules such as adamantane in the twisted
      truncated cavity. Finally, we succeeded in synthesizing new supramolecular
      trigonal prisms from linear multinuclear zinc complexes such as p-Zn2L2 and p,p
      Zn3L3 with TCA3- in aqueous solution at neutral pH, which are stabilized by
      Zn(2+)-S- or Zn(2+)-N- coordination bonds and hydrogen bonds in aqueous solution
      at neutral pH. Thus we discovered a new approach to the design of various
      supramolecular structures in aqueous solution.

PMID- 12510388
TI  - [Physiological significance of pituitary adenylate cyclase-activating polypeptide
      (PACAP) in the nervous system].
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been conserved
      remarkably during evolution and is widely expressed in the nervous system across
      phyla. PACAP has an amino acid sequence homology of 68% with that of vasoactive
      intestinal polypeptide (VIP) and of 37% with that of secretin, indicating that
      PACAP is a member of the VIP/glucagon/secretin superfamily. PACAP exerts its
      actions via three heptahelical G-protein-linked receptors: one PACAP-specific
      (PAC1) receptor and two receptors (VPAC1 and VPAC2) shared with VIP. PACAP
      stimulates several different signaling cascades in neurons, leading to the
      activation of adenylate cyclase, phospholipase C, and mitogen-activated protein
      kinase and mobilization of calcium. Although PACAP and VIP have no apparent
      homology with calcitonin and parathyroid hormone (PTH), PAC1, VPAC, secretin,
      glucagon, glucagon-like peptide 1, growth hormone-releasing hormone, calcitonin,
      and PTH/PTH-related peptide receptors are related to each other and constitute a
      subfamily of the G-protein-coupled receptors. Distribution analysis of PACAP and
      its receptors and pharmacological studies have elucidated its pleiotropic effects
      in the central and peripheral nervous systems. However, the relevance of the
      pharmacological PACAP effects to the actual physiological activities of
      endogenous PACAP has not been addressed, because potent and selective low
      molecular-weight PACAP antagonists have not yet been developed. To assess the
      function of PACAP in vivo, we have recently generated PAC1 receptor- and PACAP
      targeted mice, and provided evidence that PACAP plays a previously
      uncharacterized role in the regulation of psychomotor behaviors. In this review,
      we focus on the physiological and or pathophysiological roles mediated by PACAP
      in the nervous system.

PMID- 12510389
TI  - [Structures of peptides related to the inactivation gate on sodium channels].
AB  - The peptides related to inactivation of sodium channels were synthesized by the
      solid-phase method for the purpose of proposing a more precise concept than so
      far obtained for the inactivation and to determine the main factors that control
      inactivation. The three-dimensional structures of the peptides were determined
      using 1H-NMR spectroscopy. It was newly discovered that hydrogen bonding was
      formed between the amide proton of Ile in the IFM (IFM1488-1490) motif of the III
      IV linker and the hydroxyl oxygen atom of the side chain of Thr located adjacent
      to the IFM motif. This hydrogen bonding characterizes the structure around the
      IFM motif. By calculating the solvent-accessible surface area of the peptide
      corresponding to the III-IV linker, it was found that a hydrophobic cluster was
      formed. The hydrophobic cluster stabilizes the structure of the IFM motif.
      Moreover, the solvent-accessible surface area of the IFM motif correlated with
      the sustained currents of the incompletely inactivated sodium channels. The free
      energy of stabilization by hydrophobic interactions (delta G, -3.9 kcal mol-1),
      which is calculated from the solvent-accessible surface area for the IFM motif
      (195 A2), was in good agreement with that calculated for the equilibrium between
      the open and the inactivated states of the sodium channels (-4.1 kcal mol-1). The
      structure of the III-IV linker peptide in a phosphate buffer also formed a
      hydrophobic cluster, as well as in SDS micelles, although no hydrogen bonding was
      formed. This distinction results in the following conformational change in the
      IFM motif: in SDS micelles, the side chains of Ile and Phe in the IFM motif were
      directed to the hydrophobic cluster, whereas those in a phosphate buffer were
      directed opposite to the cluster and solvent exposed. The secondary structures of
      IIIS4-S5 and IVS4-S5, which are considered to form a receptor site, assumed alpha
      helical conformations around the N-terminal half of the sequences. The residue
      A1329 in MPD3, which is considered to interact with F1489 of the IFM motif, was
      found to locate within the alpha-helix. A hydrophobic cluster was formed on one
      side of the helix of MP-D4, which also plays an important role in the
      inactivation. A new concept for the process of fast inactivation is presented. In
      response to the voltage-dependent activation and the movement of the S4 segments,
      the two hydrophobic clusters due to the IVS4-S5 and the III-IV linker interact
      with each other. This interaction increases the hydrophobicity around the IFM
      motif. The increased hydrophobicity causes the conformational switching of the
      IF1488-1489 residues to allow F1489 to interact with A1329 of IIIS4-S5 and/or
      with N1662 in IVS4-S5. As a consequence of this process, the inactivation gate
      closes.

PMID- 12510390
TI  - [Chemo-pharmaceutical studies on the glycosphingolipid constituents from
      echinoderm, sea cucumbers, as the medicinal materials].
AB  - Glycosphingolipids (GSLs), together with glycopeptides, are typical constitutents
      of various cell membranes in a wide variety of organisms. In particular, it is
      known that GSLs have numerous physiological functions due to variations in the
      sugar chain, in spite of the very small quantity of constituents. Those are
      classified into cerebrosides, sulfatides, ceramide oligohexosides, globosides,
      and gangliosides based on the constituent sugars. Gangliosides, sialic acid
      containing GSLs, are especially enriched in the brain and nervous tissues and are
      involved in the regulation of many cellular events. Recently, a number of GSLs
      have been isolated from marine invertebrates such as echinoderms, poriferans, and
      mollusks. We have also been researching biologically active GSLs from echinoderms
      to elucidate the structure-function relationships of GSLs and to develop novel
      medicinal resources. This review summarizes the structures and biological
      activities of GSLs from sea cucumbers. This study showed that the characteristics
      of GSLs and structure-activity relationships had neuritogenic activity toward the
      rat pheochromocytoma cell line PC12. That is, most of the cerebroside
      constituents of the sea cucumber are same glucocerebrosides as in other animals,
      except for some constituents, while the ganglioside constituents were unique in
      that a sialic acid directly binds to the glucose of cerebroside, they are
      mutually connected in tandem, and some are located in the internal parts of the
      sugar chain. It also became apparent that sialic acid is indispensable for the
      neuritogenic activities.

PMID- 12510391
TI  - Pharmacoeconomic evaluation of anti-hyperlipidemic agent fenofibrate.
AB  - We evaluated the economic efficiency as well as the clinical effectiveness on
      serum lipid levels of a change in drug therapy from bezafibrate or a 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor to fenofibrate. Subjects
      were 26 outpatients suffering from type IIb or type IV hyperlipidemia who visited
      our hospital between October 2000 and January 2001. Medication doses, and serum
      lipid levels were recorded prior to the change to fenofibrate and at 6 months
      after the change. Medical costs were also calculated at the same time points. A
      significant reduction in medical costs of 14.9% was observed following the change
      to fenofibrate. Serum lipid levels were not significantly different, although an
      increase in low density lipoprotein-cholesterol (LDL-cholesterol) was observed in
      patients changing from the HMG-CoA reductase inhibitor. The actual drug costs
      were reduced by 21.8% in the bezafibrate to fenofibrate group and by 23.7% in the
      HMG-CoA reductase inhibitor to fenofibrate group. Although the drug costs of
      changing to fenofibrate decreased significantly, other costs remained almost
      unchanged.

PMID- 12510392
TI  - [Effect of admixture of betamethasone butyrate propionate ointment on
      preservative efficacy].
AB  - Twenty percent of dermatologists have experienced a separation of water or
      deterioration of topical corticosteroids mixed with commercially available
      ointments and/or creams. However, few investigations of this deterioration of
      admixtures have been reported. To assess the effects of preservatives in
      preventing microbial contamination of these admixtures, we attempted to
      investigate the concentration of preservative agents in admixtures and the
      microbial contamination of these admixtures with a topical corticosteroid
      ointment (Antebate). The concentration of parabens was reduced by half using an
      admixture of corticosteroid ointment with four types of moisturizing creams,
      Urepearl, Pastaronsoft, Hirudoid, and Hirudoidsoft. After a further 3 months, no
      decrease in parabens was seen. No microbial contamination was found in any
      admixture stored at room temperature for 1 week and touched two times daily with
      a finger. The concentration and ratio of the parabens in the aqueous phase and
      oil phase were entirely different in the admixtures before being centrifuged. The
      aqueous phase of the admixtures of the oil/water (O/W)-type emulsions of Urepearl
      and Hirudoid was not found to have microbial contamination immediately after
      being centrifuged. All aqueous phases stored at room temperature or in a
      refrigerator for 1 week and touched with a finger twice daily exhibited microbial
      contamination. These experiments demonstrated that O/W-type emulsions, in which
      the water easily separates from the bases, should be thoroughly mixed to prevent
      microbial contamination.

PMID- 12510393
TI  - [Neurological complication in 3 children with acute otitis media].
AB  - Three boys aged 6, 7 and 4 years, had experienced fever, vomiting, headache
      and/or an otorrhoea for about a week. Then the clinical picture of acute otitis
      media exacerbated by a thrombosis of a sigmoid sinus in the 4- and 6-year-old and
      by brain infarcts in the 7-year-old. Treatment consisted of antibiotics and the
      youngest two also underwent surgery. The 6-year-old made a good recovery, the 7
      year-old retained motor aphasia and hemiparalysis and the 4-year-old died.
      Although the incidence of acute otitis media complications has decreased since
      the widespread introduction of antibiotics, the complications are severe enough
      to warrant particular care in the treatment of these patients. The early
      recognition of a complicated acute otitis media and the immediate start of an
      appropriate therapy may lower the morbidity and mortality rates associated with
      this condition.

PMID- 12510394
TI  - [Publication of the results in all Dutch centers for in vitro fertilization: an
      important step towards an improvement in the effectiveness of the treatment].
AB  - For the first time, the results from all 13 in vitro fertilisation (IVF) centres
      in the Netherlands have been published in the scientific literature. The Dutch
      IVF system is unique in many respects, especially with regard to the limited
      number of high-volume centres, the widespread use of transport IVF and the
      complete coverage by health insurance companies. IVF is frequently applied,
      resulting in an amazing I IVF child out of every 60 children born in the
      Netherlands. The reported ongoing pregnancy rates per started IVF cycle (21%) are
      comparable with those in other European countries, but lower than in the United
      States. However, the number of embryos transferred is relatively low (a maximum
      of 2), resulting in a very low risk of higher order multiple pregnancies. Even
      twin pregnancies remain the most dangerous health issue associated with IVF. In
      order for IVF to move forward, a shift in paradigms is urgently required. The
      surrogate endpoint of 'pregnancies per treatment cycle' should be replaced by the
      alternative measure of 'healthy children born per started IVF treatment' in
      relation to patient discomfort, side effects, chances for (long-term) health
      risks, and costs.

PMID- 12510395
TI  - [Indications for in vitro fertilization: comparison of the Dutch guidelines with
      the published evidence].
AB  - The guideline 'Indications for in vitro fertilisation (IVF)' of the Dutch Society
      for Obstetrics and Gynaecology (Dutch acronym: NVOG) reports limited
      international evidence on this subject. A review of the published studies of
      effectiveness and cost-effectiveness shows that the possibilities to compare the
      studies and to translate the results to the diagnostic indications according to
      the Dutch guideline are indeed limited. This is due to differences in the study
      populations, different outcome measures and differences in the severity of the
      underlying pathology. The results of foreign cost-effectiveness studies cannot
      easily be generalised to the Dutch situation due to differences in the
      consumption of medical care, the policy as to indications and the price
      structure. For the indications inoperable tubal pathology and, to a lesser
      extent, severe male subfertility there is sufficient evidence-based support for
      the (cost-)effectiveness of IVF or intracytoplasmic sperm injection (ICSI) in
      comparison to waiting for spontaneous pregnancy to occur. There is insufficient
      current literature to support recommendations for the other causes of infertility
      as given in the Dutch guideline.

PMID- 12510396
TI  - [Thrombotic microangiopathy: thrombocytopenia and hemolytic anemia].
AB  - Thrombotic microangiopathy is an acute and severe syndrome characterised by a
      combination of thrombocytopenia, haemolytic anaemia with a negative direct
      antiglobulin test, and fragmentocytes in the blood smear. The condition can be
      idiopathic but can also be caused by various underlying diseases. The main causes
      are thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. By
      measuring the von Willebrand factor cleaving protease activity, it now appears
      possible to distinguish between the different causes of thrombotic
      microangiopathy, although the sensitivity and specificity of this measurement
      still need to be clarified. In patients with haemolytic uraemic syndrome without
      preceding diarrhoea, one should search for infectious foci outside the
      gastrointestinal tract, using a polymerase-chain reaction to detect the two
      different verotoxin genes where necessary. Plasmapheresis treatment has reduced
      the fatality rate amongst patients with thrombotic thrombocytopenic purpura from
      90% to 10-25%. Since patients benefit most from rapid institution of treatment,
      yet the diagnostics currently take several days, the recommendation in case of
      doubt regarding the original diagnosis is to apply initial plasma exchange
      therapy to all patients with thrombotic microangiopathy.

PMID- 12510397
TI  - [Sequential analysis in clinical and epidemiological research].
AB  - In clinical trials and epidemiological studies, interim analyses are usually
      performed for ethical or economical reasons, although efficiency aspects can also
      be a reason. The analysis is referred to as group-sequential analysis or
      continuous-sequential analysis, dependent on the number of interim analyses
      performed. Repeated testing of cumulative data requires an adjustment to the
      significance level or type I error alpha of a statistical test. On average a
      (group-)sequential analysis of a clinical or epidemiological study requires less
      patients than the analysis of a fixed-sample study.

PMID- 12510398
TI  - [Diagnostic image (117). A man with frequent blood transfusion and blister on his
      fingers. A form of porpheria cutanea tarda caused by excess iron].
AB  - A 70-year-old man with primary myelofibrosis was treated with hydroxycarbamide
      and blood transfusions. He developed porphyria cutanea tarda.

PMID- 12510399
TI  - [From gene to disease; genetic causes of hearing loss and visual impairment
      sometimes accompanied by vestibular problems (Usher syndrome)].
AB  - Usher syndrome is an autosomal recessively inherited disease, characterised by
      sensorineural hearing loss, tapetoretinal degeneration and in some cases
      vestibular problems. Based on the clinical heterogeneity, the disease can be
      classified into three clinical types (I, II and III), which have their own
      genetic subtypes (Usher 1A-Usher IG, Usher 2A-Usher 2C and Usher 3). The majority
      of the Usher type I cases are caused by mutations in the MYO7A gene (Usher 1B)
      while mutations in the USH2A gene (Usher 2A) are the cause of most cases of type
      II. Usher syndrome type III, caused by mutations in the USH3 gene, is frequently
      seen only in Finland.

PMID- 12510400
TI  - [Results of in vitro fertilization in the Netherlands, 1996-2000].
AB  - OBJECTIVE: To describe the annual results in all 13 Dutch in vitro fertilisation
      (IVF) centres in the period 1996-2000, and to look for possible differences
      between individual centres and years. DESIGN: Retrospective data collection,
      description and analysis. METHOD: The results collected on the website of the
      Dutch Society of Obstetrics and Gynaecology (Dutch acronym: NVOG; www.nvog.nl) in
      the period 1996-2000 were integrated and described, with special attention to
      possible differences between centres and years. RESULTS: In 1996-2000 (5 years),
      63,414 IVF or ICSI treatment cycles were started in the Netherlands, and 5,884
      transfers of cryopreserved embryos were performed. The number of treatment cycles
      increased over the years, particularly the number of ICSI cycles. The total
      number of ongoing pregnancies was 12,991 (20.5% per started cycle; 22.5% for ICSI
      and 18.3% for IVF). Particularly during the first 3 years, there was an increase
      in these percentages (IVF: from 16.4% (1996) to 19.2% (1998); ICSI: from 18.3%
      (1996) to 23.9% (1998)). There were differences between the centres in both the
      percentage of ongoing pregnancies per started IVF/ICSI cycle (range 13.7-25.1%)
      and the percentage ICSI (14-61%) and cryo-transfers per total number of treatment
      cycles (0-26%). It was estimated that, during this 5-year period, 1 out of every
      61 Dutch neonates resulted from IVF or ICSI. CONCLUSION: The pregnancy-rates
      after IVF and ICSI increased during the study period, and were comparable with
      the rates in other European countries. Some important data are still missing from
      the inventory, for example regarding the number of embryos per transfer, multiple
      pregnancies, live births, congenital malformations and complications.

PMID- 12510401
TI  - [The emotional burden of artificial insemination: increased anxiety and
      depression following an unsuccessful treatment].
AB  - OBJECTIVE: Determination of the emotional burden of the first IVF or ICSI
      treatment cycle, the effect of the treatment on the marital relationship, and the
      course of the treatment following a failed and a successful first attempt.
      DESIGN: Descriptive longitudinal study with repeated measures before and after
      the first treatment cycle. METHOD: 240 women and 219 men filled in questionnaires
      both before and after the first treatment cycle in the area of anxiety,
      depression, and the marital relationship (as measured with the 'Spielberger state
      trait anxiety inventory' (STAI), the 'Beck depression inventory for primary care'
      (BDI-PC) and the 'Maudsley marital questionnaire' (MMQ), respectively), as well
      as their plans for further treatment. RESULTS: After a first failed treatment
      cycle, both women and men showed an increase in depression, while women also
      showed increased anxiety. No differences were found between pre- and post
      treatment levels of anxiety and depression after a successful treatment. After
      the first failed cycle, almost 13% of the women showed clinically relevant forms
      of depression. There was an increase in dissatisfaction with the sexual
      relationship in both men and women regardless of the success of the treatment.
      Before the start of the first treatment cycle, 2% of the couples had no intention
      to undergo further treatment if the first cycle failed; none of these couples
      started a new cycle. Ultimately, 18% of the couples refrained from further
      treatment following a failed first treatment cycle. CONCLUSION: After a failed
      first treatment cycle the couples showed an increase in depression and one in
      eight women had a clinically relevant form of depression. More than one out of
      every 6 couples decided to refrain from further treatment after a failed first
      cycle.

PMID- 12510402
TI  - [Maternal complications of fetal hydrops].
AB  - Three women, aged 28, 27 and 25 years, two primigravidae and one woman who had
      given birth to a hydropic child previously, had four pregnancies with hydrops of
      the foetus and the placenta: two (in the same patient) due to foetal
      cardiomyopathy and two with foetal heart block. The patients developed severe
      oedema and preeclampsia. After the delivery they recovered well. Since the
      introduction of anti-D rhesus immunoprophylaxis, foetal hydrops has become less
      frequent. The resulting maternal complications (the maternal hydrops syndrome and
      enlarged polycystic ovaries) are therefore less well-known. Serious maternal
      complications occur in around 50% of cases of foetal hydrops. Careful monitoring
      of the maternal condition in cases of foetal hydrops is therefore warranted.

PMID- 12510403
TI  - [Methemoglobinemia due to ingestion of isobutyl nitrite ('poppers')].
AB  - Two male students, aged 20 and 21 years, developed central cyanosis shortly after
      drinking 5 ml of 'poppers' (isobutyl nitrite). They presented with
      methaemoglobinaemia and were hospitalised. After treatment with oxygen and
      intravenous fluids they could be discharged in good health the following day.
      Poppers are alkyl nitrites with vasdilative and oxidizing properties. They are
      used as party drugs (i.e. inhaled) because of their short-lived euphoric effect.
      Overdose can result in methaemoglobinaemia: the presence of oxidized haemoglobin
      which is unable to transport oxygen. Depending on the serum level of
      methaemoglobin this may result in central cyanosis, unconsciousness, coma and
      even death. Patients with high methaemoglobin levels should be treated with i.v.
      methylene blue.

PMID- 12510404
TI  - [Obstacles to the routine discussion with hospital patients of possible
      cardiopulmonary resuscitation].
AB  - Nowadays, cardiopulmonary resuscitation is not routinely discussed with all
      hospital patients, even though it should be for a number of reasons. First of
      all, every patient may suffer cardiac arrest, and the overall outcome of a
      subsequent attempt at resuscitation is difficult to predict. Besides, patients
      who do not wish to be resuscitated often do not tell that to the physician of
      their own accord. Patients should therefore be more actively informed and
      encouraged to express their own preferences. The routine discussion of possible
      resuscitation gives physicians the opportunity to discuss, determine and delimit
      the extent of the intended medical procedure. In the literature, communication
      problems in three different areas can be identified as a cause of the present
      situation. These are--for both physician and patient--inability, lack of insight
      and unwillingness to discuss resuscitation. Physicians should be aware of the
      identified communication problems and deal with them in a professional manner. An
      understanding of these problems forms the basis for a broader implementation of
      resuscitation discussions in hospitals.

PMID- 12510405
TI  - [The treatment of carpal tunnel syndrome].

PMID- 12510406
TI  - [Treatment of patients with a TIA or a stroke].

PMID- 12510407
TI  - [Treatment of patients with a TIA or a stroke].

PMID- 12510408
TI  - [Treatment of patients with a TIA or a stroke].

PMID- 12510409
TI  - [Treatment of patients with a TIA or a stroke].

PMID- 12510410
TI  - [The treatment of hypomagnesemia].

PMID- 12510411
TI  - [Karl Landsteiner (1868-1943) and the specificity of serological reactions, one
      hundred years ago and now].

PMID- 12510412
TI  - [Are leukotriene antagonists effective in bronchial asthma?].

PMID- 12510413
TI  - [Use of ursodeoxycholic acid combined with silymarin in the treatment of chronic
      ethyl-toxic hepatopathy].
AB  - 30 patients, affected by chronic ethylic hepatopathy, were treated with 450
      mg/daily of ursodeoxycholic acid (UDCA): after six months, a significant decrease
      of serum hepatic enzymes was noted. The addition of silymarin (400 mg/daily) to
      UDCA in other 30 patients, induced a further improvement of hepatic function.

PMID- 12510414
TI  - Higher blood pressure load (baric impact) in normotensives with endothelial
      dysfunction: a paraphysiological status of "pre-hypertension".
AB  - PURPOSE: The present study investigated the blood pressure (BP) load (L), namely
      Baric Impact (BI), in normotensives with and without endothelial dysfunction
      (ED). The aim was to detect baric differences supporting the thesis that the ED
      is associated with vasopressant effects that are responsible for a
      paraphysiological condition of higher BP (pre-hypertension) even in
      normotensives. MATERIALS AND METHODS: Thirty-eight normotensives were
      investigated in their endothelium-dependent vasomotricity by mean of the non
      invasive post-ischemic brachial artery vasodilation test. Additionally, their
      underwent a non-invasive ambulatory (A) BP monitoring (M) over the 24-h span in
      order to confirm that they were not hypertensive. The ABPM served also to compute
      the systolic (S) and diastolic (D) BI. RESULTS: The ED was detected in eight
      normotensives of the investigated group. These cases with ED were found to show a
      significantly higher SBI and DBI as compared to the normotensives without ED.
      CONCLUSIONS: The significant elevation of the SBI and DBI in normotensives with
      ED is an evidence convincing that a dysfunctional endothelium is responsible for
      vasopressant effects that cause a paraphysiological status of "pre-hypertension".

PMID- 12510415
TI  - [Effectiveness and safety of montelukast versus budesonide at various doses on
      bronchial reactivity in subjects with mild persistent asthma].
AB  - PURPOSE: Insufficient data exist to evaluate the comparative effects of inhaled
      corticosteroids versus leukotriene receptor antagonists on airway inflammation
      and remodelling. The aim of the study was to evaluate the effectiveness and
      safety of montelukast versus budesonide at different doses on bronchial
      reactivity in mild-asthmatic adult patients. PATIENTS AND METHODS: A total of 40
      patients were randomly assigned to a different treatment and divided in 2
      treatment groups (A, B) as follows: A-10 mg of montelukast daily; B-400 mg of
      budesonide twice a day. RESULTS: We studied 40 subjects (21 males, 19 females)
      divided in two groups of 20 subjects each: group A with mean age 25.16 +/- 7.68
      years, group B with mean age 26.18 +/- 6.15 years. After 16 weeks of treatment in
      the group A the PC20 (provocative concentration of methacholine which cause a
      fall of FEV1 > or = 20%) was 620.12 +/- 140.54 micrograms/mL significantly highly
      compared to basal value of 315.75 +/- 100.16 micrograms/mL (p < 0.02). In the
      group B the PC20 was 795.67 +/- 312.76 micrograms/mL significantly highly
      compared to basal value of 342.87 +/- 132.38 micrograms/mL (p < 0.001). We not
      found differences in FEV1, FVC e PEF before and after the treatment. CONCLUSIONS:
      Montelukast may be considered a valid alternative in the treatment of mild
      persistent asthma, both for the benefits on bronchial reactivity and for the
      great advantage of the once-daily dosage, which consistently improves the
      compliance with the chronic treatment of the disease.

PMID- 12510416
TI  - [Utility of endoscopic follow-up after resection of colorectal cancer].
AB  - PURPOSE: Patients resected for colorectal cancer are at increased risk for an
      anastomotic recurrence, for adenomatous polyps and for a metachronous cancer. A
      regular colonoscopic surveillance in these patients is justified for early
      detection and potential resection of anastomotic recurrences, new primary cancer
      and adenomatous polyps. PATIENTS AND METHODS: 322 patients were observed and
      resected for colorectal cancer between 1970 and 1988, with complete staging
      agreed to be included in a follow-up program (median follow-up: 105 months). To
      December 1993 all the patients were submitted to colonoscopy once yearly for the
      first 5 years and then every 2 years. RESULTS: Anastomotic recurrence was
      observed in 22 of the 253 patients who underwent resection for rectal or sigmoid
      adenocarcinoma (8.7%). Sixteen of these patients were submitted to a second
      curative resection with a median survival of 35 months; the median survival was 6
      months in the 6 patients who could not undergo this operation (p = 0.0018).
      Metachronous adenomas of the residual colon were found in 24 patients (7.4%) and
      metachronous cancers in 5 (1.5%) at Stage A, according to Dukes' classification.
      CONCLUSIONS: In patients resected for rectal or sigmoid carcinoma, a
      sigmoidoscopy should be performed every 6 months for the first 2 years for the
      early detection of anastomotic recurrences. In all cases, a colonoscopy should be
      performed every 5 years after surgery to detect metachronous lesions at early
      stage. Before surgery, a "clean colon" should always be established to detect
      possible synchronous lesions.

PMID- 12510417
TI  - [New risk factors of cardiovascular diseases].

PMID- 12510418
TI  - [Guidelines for the management of hypertensive crises and simple blood pressure
      rise. Literature review and clinical experience].
AB  - Hypertension is a common clinical problem in the Emergency Department. Beside
      homologated therapeutical approaches it is necessary in primis to consider the
      problem in a clinical context and in an appropriate nosographic scheme in order
      to provide a rational approach to the treatment. In this paper the authors review
      the nosographic and therapeutical approaches previously reported in literature
      and then state their proposals derived by their daily experience at the Emergency
      Department. In authors' opinion it is of primary importance to distinguish
      between hypertensive crises and simple blood pressure rise. For this end it seems
      useful to define four syndromic classes: A. Real Hypertensive Crises: 1
      Hypertensive Emergencies, 2-Hypertensive Urgencies. B. Simple Blood Pressure
      Rise: 1-Stable Uncomplicated Hypertension, 2-Transient Hypertension. According to
      this classification the majority of patients referring to Emergencies Departments
      for elevated blood pressure can be included in the last two classes. The authors
      suggest a step-by-step approach to the treatment beginning with benzodiazepines,
      loop diuretics, beta-blockers or clonidine or ACE inhibitors or calcium channel
      blockers; In an elevated percentage of cases benzodiazepines alone are effective
      in appropriately lowering blood pressure.

PMID- 12510419
TI  - [Preventive and therapeutic approach to tuberculosis in the general, and high
      risk populations].
AB  - Authors in the present contribute illustrate the tuberculosis disease in all
      aspects, the infection, the disease in active phase and in the resistant phase,
      the law, the prevention and the professional risk in exposed subject, and to
      consider the epidemiological aspect. Authors hope a coordinate approach between
      the different figure involved in the therapy and prevention of tuberculosis
      disease.

PMID- 12510420
TI  - [Bacterial vaginosis and pregnancy].
AB  - Premature rupture of membranes (PROM) occurs in approximately 5-10% of all
      pregnancies and is implicated in approximately one third of preterm births. PROM
      is associated with increased risks of perinatal as well as maternal morbidity and
      mortality at every gestational age. Much information suggest that the presence of
      bacterial vaginosis may be implicated in the occurrence of PROM and subsequent
      preterm delivery in significant numbers of pregnant women. We will briefly review
      clinical and pathophysiologic information linking bacterial vaginosis and PROM.

PMID- 12510421
TI  - [Esthesioneuroblastoma. Description of a case investigated with CT and MR].
AB  - Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a rare
      neuroendocrine tumor originating from the olfactory epithelium of the upper nasal
      cavity and representing < 3% of all tumors of the nasal cavities. This malignant
      tumor is characterized by a slow growth and local recurrencies and has a more
      favorable prognosis as compared with other more frequent forms of neuroblastomas
      originating from the suprarenal medulla and the sympathetic nervous system.
      Affected patients usually present with a history of progressive nasal
      obstruction, rhinorrhea, and severe epistaxis--sign of the conspicuous
      vascularity of this type of tumor. The combined use of CT and MR techniques
      allows the diagnostic suspicion of esthesioneuroblastoma and is of vital
      importance in the accurate staging of the disease and in the treatment planning.

PMID- 12510422
TI  - [Nutritional evaluation and diet therapy of patients with chronic liver disease].
AB  - Malnutrition is prevalent in patients with advanced chronic liver disease and may
      be associated with a worse prognosis. Treatments often include many dietary
      restrictions (regarding fluids, sodium and proteins), which may further limit
      energy intake in addition to other factors limiting food intake (e.g. anorexia,
      encefalopathy). Guidelines for an optimal diet therapy in patients with different
      liver diseases, above all in presence of encefalopathy, are briefly reported.

PMID- 12510423
TI  - [Diastolic cardiac insufficiency].

PMID- 12510424
TI  - [Dust on the soul].

PMID- 12510425
TI  - [Humor in nursing care. "This is not what we need just now..."].

PMID- 12510426
TI  - [Dehydration in the terminal phase. Allowing the process of dying to take its
      course].

PMID- 12510427
TI  - [The nursing process. The key in nursing care].

PMID- 12510428
TI  - [Basel drug treatment center. "An environment where I feel comfortable"].

PMID- 12510429
TI  - [Violence and helplessness].

PMID- 12510430
TI  - [Patient education for patients treated with anticoagulants. Nursing care, a
      relationship voyage].

PMID- 12510431
TI  - [Social construction of nursing care. Words in nursing care].

PMID- 12510435
TI  - Driven to serve.

PMID- 12510432
TI  - [Working conditions. Does the work endanger mental health of nursing?].

PMID- 12510436
TI  - My greatest fear.

PMID- 12510437
TI  - Clergy on call.

PMID- 12510438
TI  - Dying well. A father's lesson.

PMID- 12510439
TI  - Why not laugh?

PMID- 12510440
TI  - Co-pay or cover charge?

PMID- 12510441
TI  - Putting stock in the spiritual.

PMID- 12510442
TI  - Faith's impact on health. Implications for the practice of medicine.
AB  - The role of religiousness/spirituality (R/S) in health has been of growing
      interest in the medical literature in recent years. Studies have demonstrated
      enhanced health effects from religious prescriptions and proscriptions,
      religious/spiritual social support, and specific attitudes and behaviors linked
      to deep spiritual belief (e.g., compassionate view toward others and active
      religious surrender). This article reviews the recent literature on the role of
      R/S in health and offers suggestions on how physicians can explore whether their
      patient's R/S is a source of strength. Examples of simple questions that can be
      incorporated into a routine visit are presented. Physicians who ask about R/S
      issues may help patients recognize new ways of coping, new avenues for social
      support, and new sources of courage and hope.

PMID- 12510443
TI  - Peripartum cardiomyopathy. Insights from Haiti regarding a disease of unknown
      etiology.
AB  - Peripartum cardiomyopathy (PPCM) is a disease of unknown etiology characterized
      by the onset of left ventricular failure during the period of 1 month antepartum
      to 5 months postpartum. The PPCM Project at Hospital Albert Schweitzer (HAS) in
      Haiti has identified 78 cases of PPCM since February 1, 2000, representing an
      incidence of 1 case per 350 to 400 live births, which is severalfold the
      estimated incidence in the United States. The reasons for this high incidence in
      Haiti are unknown. Ongoing investigations have identified the presence of several
      anticardiac antibodies in many women at HAS who have PPCM, suggesting that PPCM
      is a unique form of dilated cardiomyopathy and supporting the hypothesis that
      PPCM has an autoimmune basis. Identification of a high-incidence area for PPCM
      presents a unique opportunity to make progress in defining potential risk
      factors, identifying high-risk mothers, detecting underlying etiologies, and
      discovering more effective new treatments of this often-fatal disease.

PMID- 12510444
TI  - Acute care for alcohol intoxication. Be prepared to consider clinical dilemmas.
AB  - The clinical assessment of an acutely intoxicated patient should be performed
      with meticulous care and include repetitive examinations to properly determine
      the patient's condition. Multiple factors, such as trauma and concomitant use of
      other drugs, can confuse the diagnostic picture and affect the choice of therapy.
      In this article, Dr Yost reviews the diagnostic considerations, appropriate
      treatment, and clinic discharge for the intoxicated patient.

PMID- 12510445
TI  - Alcohol use disorders in women. Screening methods and approaches to treatment.
AB  - Primary care physicians have a unique opportunity to educate women about alcohol
      use and to identify those with alcohol problems. Early identification and
      intervention can significantly limit the adverse consequences of alcohol abuse.
      To identify alcohol abuse and intervene most effectively, physicians need to
      recognize the differences in risk factors, presentation, and treatment relevant
      to women.

PMID- 12510446
TI  - Unraveling the mystery of rosacea. Keys to getting the red out.
AB  - Few medical disorders so clearly and publicly display our internal physiology as
      rosacea. Although the basic pathophysiologic aspects of this enigmatic disorder
      remain mysterious, our ability to improve and control it is increasing. In this
      article, Dr Landow describes the subtypes and variations of rosacea, discusses
      disease triggers, and emphasizes the importance of lifestyle modification in
      combination with pharmacologic therapy.

PMID- 12510447
TI  - Routine bone densitometry in elderly men?

PMID- 12510448
TI  - The many causes of headache. Migraine, vascular, drug-induced, and more.
AB  - Accurate diagnosis of headache can be challenging when the pain pattern and the
      source are not immediately recognized. The most common types of headache are
      primary (i.e., migraine, tension-type, and cluster). In addition, many secondary
      causes of head pain have been identified. Dr Levin reviews the major types of
      headache as categorized by the International Headache Society and provides a list
      of red flags that may signal a secondary headache.

PMID- 12510449
TI  - Atypical antipsychotics for acute agitation. New intramuscular options offer
      advantages.
AB  - Violent or threatening behavior is a common reason for a visit to the emergency
      department. Patients with aggressive behavior must first be assessed for the
      possibility of comorbid medical conditions, which can complicate management. The
      introduction of intramuscular preparations of atypical antipsychotics provides
      new treatment options for acute agitation. These agents appear to be fast-acting
      and well tolerated and do not induce the akathisia of the older neuroleptic
      agents. Short-term sedation with lorazepam remains a safe and effective choice
      for managing acute agitation, in particular when withdrawal from alcohol may be a
      precipitating factor. However, lorazepam does not address the psychotic symptoms
      that may be at the core of much of this behavior. The intramuscular preparations
      of the atypical antipsychotics will probably supplant the intramuscular
      formulations of the older neuroleptics, much in the same way that the oral forms
      of these agents have become the agents of choice in treating psychosis. In
      addition, development of depot preparations of atypical antipsychotics is
      progressing rapidly. These products may further revolutionize the emergency and
      postemergency care of psychotic patients.

PMID- 12510450
TI  - More than a hand infection. Pyoderma gangrenosum.

PMID- 12510451
TI  - Patient notes: pancreatitis.

PMID- 12510452
TI  - The role of esophagogastroduodenoscopy in the diagnosis and management of upper
      gastrointestinal disorders.
AB  - Esophagogastroduodenoscopy has revolutionized the clinical management of upper
      gastrointestinal diseases. Millions of EGDs are performed annually in the United
      States for many indications, such as gastrointestinal bleeding, abdominal pain,
      dysphagia, or surveillance of premalignant lesions. Esophagogastroduodenoscopy is
      very safe, with a low risk of serious complications such as perforation,
      cardiopulmonary arrest, or aspiration pneumonia. It is a highly sensitive and
      specific diagnostic test, especially when combined with endoscopic biopsy.
      Esophagogastroduodenoscopy is increasingly being used therapeutically to avoid
      surgery. New endoscopic technology such as endosonography, endoscopic sewing, and
      the endoscopic videocapsule will undoubtedly extend the frontiers and increase
      the indications for endoscopy.

PMID- 12510453
TI  - The role of sigmoidoscopy and colonoscopy in the diagnosis and management of
      lower gastrointestinal disorders: technique, indications, and contraindications.
AB  - Flexible sigmoidoscopy and colonoscopy have revolutionized the clinical
      management of colonic diseases. Colonoscopy has a broad range of indications,
      including evaluating lower GI symptoms such as lower GI bleeding, evaluating
      abnormal radiographic findings, and screening and surveillance for colon cancer.
      Colonoscopy is increasingly being used therapeutically. Patient evaluation,
      patient instructions, and colonic preparation before colonoscopy are essential
      for safe and efficient colonoscopy. Intravenous sedation reduces patient pain and
      anxiety during colonoscopy, but requires monitoring by pulse oximetry and
      automated measurements of vital signs. An experienced colonoscopist can complete
      colonoscopy in 90% or more of cases, using maneuvers to maintain the colonic
      lumen in view, straighten the colonoscope, and avoid looping during colonic
      intubation.

PMID- 12510454
TI  - The role of sigmoidoscopy and colonoscopy in the diagnosis and management of
      lower gastrointestinal disorders: endoscopic findings, therapy, and
      complications.
AB  - Flexible sigmoidoscopy and colonoscopy have revolutionized the clinical
      management of colonic diseases. Colonoscopy is a highly sensitive and specific
      test. Colonic diseases often produce characteristic colonoscopic findings, as
      well as characteristic histologic findings, as identified in colonoscopic biopsy
      or polypectomy specimens. Colonoscopy is relatively safe, with a low incidence of
      serious complications, such as colonic perforation, hemorrhage, cardiopulmonary
      arrest, or sepsis. Colonoscopy is becoming more important clinically because of
      more widespread use of screening colonoscopy for colon cancer, application of
      therapeutic colonoscopy, and exciting new technical improvements.

PMID- 12510455
TI  - Gastrointestinal endoscopic ultrasonography.
AB  - Although conventional endoscopy provides excellent visualization of
      gastrointestinal mucosa, it provides little information about intramural or
      nearby extramural lesions. The imaging of intraabdominal structures by
      conventional transabdominal ultrasound is degraded by ultrasound energy
      attenuation with distance. The provision of an ultrasound probe on a flexible
      gastrointestinal endoscope, to form an echoendoscope, provides excellent imaging
      of the gastrointestinal wall and of adjacent extramural structures. During the
      last two decades, endoscopic ultrasound, using an echoendoscope, has
      revolutionized the diagnosis and treatment of gastrointestinal diseases that
      affect the submucosa, deep bowel wall, and adjacent extramural structures. This
      article reviews the role of endoscopic ultrasound in the diagnosis and treatment
      of gastrointestinal disease, including standard and promising new applications,
      as well as standard and emerging new technology.

PMID- 12510456
TI  - Recent advances in the endoscopic diagnosis and therapy of upper
      gastrointestinal, small intestinal, and colonic bleeding.
AB  - Endoscopy has become the first and primary diagnostic and therapeutic modality in
      the management of patients with severe gastrointestinal bleeding. Panendoscopy,
      push enteroscopy, and colonoscopy provide the diagnostic, prognostic, and
      therapeutic elements to improve patient outcomes and to reduce morbidity and
      mortality from severe GI hemorrhage. Recent improvements in endoscopic hemostatic
      techniques and in imaging modalities using wireless capsule endoscopy suggest
      that diagnostic and therapeutic endoscopy will be even more important in
      determining patient outcomes in the future.

PMID- 12510457
TI  - Radiologic diagnosis and treatment of gastrointestinal hemorrhage and ischemia.
AB  - Major breakthroughs in catheter, guidewire, and other angiographic equipment
      currently allow interventional radiologists to diagnose massive life-threatening
      upper and lower GI hemorrhage and to stop the bleeding safely and effectively
      using superselective catheterization and microcoil embolization. Similarly, the
      interventional radiologist can treat acute intestinal ischemia safely and
      effectively with selective catheterization and papaverine administration and
      treat chronic mesenteric ischemia by percutaneous angioplasty and stent
      placement. A multidisciplinary approach, including the gastroenterologist,
      radiologist, and surgeon, is critical in managing GI bleeding and intestinal
      ischemia, particularly in patients at high risk or presenting as diagnostic
      dilemmas.

PMID- 12510458
TI  - Laparoscopic gastrointestinal surgery.
AB  - In the short time since LC was first performed in humans, minimal-access surgical
      techniques have been applied to the full spectrum of surgical therapy of
      gastrointestinal diseases. For many gastrointestinal diseases, [figure: see text]
      laparoscopy seems to offer advantages over traditional open surgery. The long
      term results of laparoscopic surgery for cancer await the results of prospective
      clinical trials currently underway and caution is urged when laparoscopic
      curative resection is performed. On the horizon are significant improvements in
      technology that should lead to further applications and advances in laparoscopic
      gastrointestinal surgery.

PMID- 12510459
TI  - Barrett's esophagus and esophageal adenocarcinoma: pathogenesis, diagnosis, and
      therapy.
AB  - Gastric juice that refluxes into the esophagus can injure esophageal squamous
      epithelium. When the injury heals through a metaplastic process in which an
      abnormal columnar epithelium replaces the injured squamous one, the resulting
      condition is called Barrett's esophagus. Gastroesophageal reflux disease and
      Barrett's esophagus are the most important risk factors for esophageal
      adenocarcinoma. This article examines such issues as the treatment, endoscopic
      surveillance, and chemoprevention of Barrett's esophagus. Also included are
      published guidelines and recommendations.

PMID- 12510460
TI  - Pathogenesis and therapy of gastric and duodenal ulcer disease.
AB  - Despite the decreasing frequency of Helicobacter pylori-induced peptic ulcers,
      peptic ulcer disease remains a major clinical problem partly because nonsteroidal
      anti-inflammatory drug ulcers have increased in frequency. The reduction in
      nonsteroidal anti-inflammatory drug ulcers by use of selective cyclooxygenase-2
      inhibitors will not eliminate the problem because of increased use of aspirin for
      cardiovascular prophylaxis. This article reviews current concepts of peptic ulcer
      pathogenesis and therapy according to ulcer etiology; discusses potential
      interactions between etiologies; and considers the therapy for H pylori infection
      including the effects of antimicrobial resistance, and the role of bismuth
      quadruple therapy or furazolidone salvage therapy.

PMID- 12510461
TI  - The molecular and genetic basis of colon cancer.
AB  - Remarkable progress has been accomplished in understanding the molecular basis of
      genetic colon cancer syndromes including FAP and HNPCC, and their variants; of
      sporadic colon cancer; and of the rare hamartomatous polyp syndromes. This
      molecular progress now has to be translated into clinical progress in molecular
      diagnosis, and in pharmacologic therapy for colonic polyps and cancers. It is
      hoped that such progress will impact on the frequency and mortality of this very
      common and frequently fatal cancer.

PMID- 12510462
TI  - Recent developments in inflammatory bowel disease.
AB  - The evolving medical armamentarium holds promise for more precise and effective
      therapies for IBD. The experience with anti-TNF therapy, particularly infliximab,
      illustrates the potential efficacy of therapies targeted at specific mediators or
      pathways involved in the pathogenesis. Advances in molecular technology have
      enabled the development of novel and potentially effective targeted therapies.
      Equally important is the increasing scientific understanding of the pathogenesis
      of IBD, which will likely improve the ability to stratify disease and to select
      therapies based on genotypic, immunologic, and phenotypic profiles in the future.

PMID- 12510464
TI  - The state of the Society.

PMID- 12510463
TI  - The irritable bowel syndrome.
AB  - Symptoms of IBS are very prevalent. One quarter of symptomatic individuals
      present for medical care because of symptom severity and psychologic factors. The
      pathogenesis of IBS is multifactorial, involving abnormalities in the gut, immune
      system, enteric sensory and motor nerves, and the CNS. IBS is diagnosed by
      symptomatology according to the Rome criteria and the absence of alarm findings
      suggestive of organic disease. Minimal testing is advocated to confirm the
      diagnosis in patients presenting with typical symptoms. Therapy is based on the
      dominant symptom (IBS subtype). Therapeutic options include dietary
      modifications, counseling, medications, and psychologic treatments. Novel
      therapies are being investigated to correct potentially pathogenetic peripheral
      and CNS abnormalities in IBS.

PMID- 12510465
TI  - Writing for publication.

PMID- 12510466
TI  - Brave new world.

PMID- 12510467
TI  - Searching for clinical significance in research results.

PMID- 12510468
TI  - Are somatostatin analogues (octreotide and lanreotide) effective in promoting
      healing of enterocutaneous fistulas?

PMID- 12510469
TI  - Risk factors associated with pressure ulcer development at a major western
      Australian teaching hospital from 1998 to 2000: secondary data analysis.
AB  - OBJECTIVE: The purpose of this study was to identify risk factors associated with
      the presence of pressure ulcer development in adult patients at an acute care
      teaching hospital. DESIGN: The database was established by combining the results
      from 3 annual cross-sectional pressure ulcer prevalence studies conducted between
      1998 and 2000. SETTING AND SAMPLE: The sample consisted of all medical and
      surgical patients who were inpatients on the day of the pressure ulcer surveys.
      The sample includes a total of 1394 patients. METHODS: This study undertook
      secondary data analysis with use of logistic regression and descriptive
      statistics. RESULTS: Overall pressure ulcer prevalence was calculated at 15.9%,
      with this figure decreasing slightly to 12.7% when pressure ulcers present on
      admission were excluded. Initial analysis identified several variables as
      significant risk factors for pressure ulcer development (age, Braden Scale risk
      category, and admission type and specialty). However, when entered into a final
      multivariate model, only 2 factors, age and Braden Scale risk category, were
      found to be significant. The odds ratio matrix revealed a consistent trend toward
      increasing odds ratios with increasing Braden Scale risk category within each age
      group. The magnitude of this trend was more pronounced in the younger age groups,
      highlighting the importance of undertaking Braden Scale assessments of younger
      patients, some of whom may be at greater risk of having a pressure ulcer develop
      than would otherwise be expected. CONCLUSION: Pressure ulcer prevalence in this
      acute care setting is high when compared with other Australian data. However,
      comparisons of pressure ulcer prevalence across studies are difficult to
      interpret because of different reporting methods. Although predictor variables
      for pressure ulcers have been identified in a number of studies, longitudinal
      studies are needed to identify the cause-and-effect relationships for potential
      predictor variables. In addition, more sophisticated statistical analyses such as
      the use of the odds ratio matrix may help guide further research into interaction
      effects between predictor variables and how these might affect the psychometric
      properties of risk assessment tools such as the Braden Scale. Pressure ulcer
      interventions should be targeted at the sacrum and heel, because these appear to
      be the most frequently observed locations for pressure ulcers.

PMID- 12510470
TI  - Comparison of interface pressures in the pediatric population among various
      support surfaces.
AB  - OBJECTIVE: The purpose of this study was to evaluate the interface pressures
      under the bony prominences of children on several support surfaces to evaluate
      benefit, in terms of the lowest interface pressures, and cost-effectiveness.
      DESIGN: A descriptive study design was used. SETTING/SUBJECTS: A convenience
      sample of 54 healthy children from the community ranging in age from infancy
      through 16 years was enrolled through advertisements in the hospital newsletter.
      The study was conducted in the General Clinical Research Center located within
      Texas Children's Hospital, Houston, Texas. INSTRUMENTS: The instrument used to
      measure the interface pressures was the Mini-Texas Interface Pressure Evaluator.
      METHODS: A comparison was done to evaluate interface pressures under the occiput
      for infants to children younger than 6 years of age and under the occiput,
      coccyx, and heel for 6- to 18-year-olds. Five surface combinations were used for
      measurements: a standard hospital bed or crib mattress; mattress with Delta foam
      overlay; a mattress with a Gel-E-Donut pillow; a mattress with a Delta foam
      overlay plus Gel-E-Donut pillow; and an Efica low-air-loss bed. RESULTS: The
      standard hospital mattress yielded the highest interface pressures. The Delta
      Foam overlay alone or in combination with the Gel-E-Donut pillow produced the
      lowest occipital pressures in all age groups. The Delta foam overlay produced
      comparable pressures to the Efica low-air-loss bed when measuring the coccyx and
      heel interface pressures. CONCLUSIONS: The Delta Foam overlay alone or in
      combination with the Gel-E-Donut pillow is a cost-effective and therapeutic
      choice for pressure reduction as demonstrated in this study of healthy children.

PMID- 12510471
TI  - Effectiveness of prompted voiding in treating urinary incontinence in cognitively
      impaired homebound older adults.
AB  - OBJECTIVE: The objective of this study was to examine the short-term
      effectiveness of prompted voiding (PV) in cognitively impaired homebound older
      adults. DESIGN: This was a prospective, controlled exploratory study with a cross
      over design where usual care controls crossed-over to the intervention following
      an 8-week observation period. SETTING: Adults aged 60 years and older with
      urinary incontinence and who met Center for Medicare and Medicaid Services
      criteria for being homebound were referred to the study by home care nurses from
      2 large Medicare-approved home health agencies in a large metropolitan county in
      southwestern Pennsylvania. Nineteen cognitively impaired older adults were
      randomly assigned to either the PV intervention or a usual care attention control
      group. MEASURES: Measures used included structured continence and medical
      histories. Older American Research and Service Physical and Instrumental
      Activities of Daily Living scales, Folstein Mini Mental State Examination, Clock
      Drawing Test, Geriatric Depression Scale, Performance-Based Toileting Assessment,
      bladder diaries, and physical examination. RESULTS: Nineteen subjects were
      randomly assigned to a PV (n = 9) or delayed attention-control group (n = 10).
      Treatment subjects with complete pretreatment and posttreatment data (n = 6)
      experienced a mean 60% reduction in daytime incontinent episodes compared with a
      mean 37% reduction among control subjects (n = 10). Following the control phase,
      subjects crossed over to the treatment protocol. A total of 15 subjects completed
      the PV protocol. Among all subjects completing the treatment protocol, there was
      a 22% reduction in daytime incontinent episodes compared with true baseline
      (immediately following the control phase for those crossing over from the control
      group). CONCLUSIONS: The PV intervention resulted in clinically significant
      reductions in urinary incontinence for many of the participants, which may be
      achievable for many cognitively impaired homebound older adults.

PMID- 12510472
TI  - Two case studies of Marjolin's ulcers in patients referred for management of
      chronic pressure ulcers.
AB  - The term "Marjolin's ulcer" is often used to describe the formation of neoplastic
      changes in the scar tissue of chronic ulcers. This type of carcinoma is most
      often seen in postburn scars, but it may be seen in many types of chronic wound
      scars. The most common cell type is squamous cell carcinoma. Squamous cell
      carcinomas resulting from Marjolin's ulcers have a much greater tendency to
      metastasize than squamous cell carcinomas arising from other causes, which makes
      early diagnosis imperative. The 2 case studies in this article describe
      Marjolin's ulcers occurring in chronic pressure ulcers, which should alert the
      clinician to the possibility of malignancy in any long-standing wound with an
      atypical presentation.

PMID- 12510473
TI  - The periapical space--a dynamic interface.
AB  - The ultimate aim of endodontic treatment is to encourage the healing of apical
      periodontitis, or to prevent it from occurring if it was not present prior to
      treatment. Apical periodontitis is a general term used to describe an
      inflammatory response to irritation caused by the contents of a root canal system
      and it has several distinct forms. The most common is a granuloma but this can
      develop into other disease entities such as an abscess, a periapical pocket cyst
      or a true cyst, all of which present as radiolucencies. However, periapical
      radiolucencies may also be caused by extra-radicular infections, foreign body
      reactions and periapical scars, or they may be due to other tumours and cysts
      that have not originated from pulp disease. Practitioners must recognise and
      understand the different pathological entities and the dynamic interactions that
      occur in the periapical tissues in order to correctly diagnose and treat these
      conditions.

PMID- 12510474
TI  - Pulpal heat changes with newly developed resin photopolymerisation systems.
AB  - Composite resin is a widely-used direct tooth coloured restorative material.
      Photoactivation of the polymerisation reaction can be achieved by visible blue
      light from a range of light sources, including halogen lamps, metal halide lamps,
      plasma arc lamps, and Light Emitting Diode (LED) lights. Concerns have been
      raised that curing lights may induce a temperature rise that could be detrimental
      to the vitality of the dental pulp during the act of photoactivation. The present
      study examined heat changes associated with standardised class V restorations on
      the buccal surface of extracted premolar teeth, using a curing time of 40
      seconds. The independent effects of type of light source, resin shade, and
      remaining tooth thickness were assessed using a matrix experimental design. When
      a conventional halogen lamp, a metal halide lamp and two different LED lights
      were compared, it was found that both LED lamps elicited minimal thermal changes
      at the level of the dental pulp, whereas the halogen lamp induced greater
      changes, and the metal halide lamp caused the greatest thermal insult of all the
      light sources. These thermal changes were influenced by resin shade, with
      different patterns for LED versus halogen or halide sources. Thermal stress
      reduced as the remaining thickness of tooth structure between the pulp and the
      cavity floor increased. From these results, it is concluded that LED lights
      produce the least thermal insult during photopolymerisation of composite resins.

PMID- 12510475
TI  - Discuss that the coronal seal is more important than the apical seal for
      endodontic success.
AB  - One of the main principles for successful root canal treatment is the prevention
      of microorganisms and toxins from the oral flora penetrating through the root
      canal system into the periapical tissues (1). This is achieved by obturating the
      root canal system completely, including the coronal and apical ends. Inadequate
      obturation of the root canal system has been found to be the most frequent cause
      of failure after endodontic treatment (2). A number of studies have indicated
      that leakage, whether from a coronal or apical direction, adversely affects the
      success of root canal treatment (3-7). The significance of the coronal seal has
      been increasingly recognized in the dental literature (4, 5, 8, 9) and in more
      recent times, it has been suggested that apical leakage may not be the most
      important factor leading to the failure of endodontic treatment--but that coronal
      leakage is far more likely to be the major determinant of clinical success or
      failure (10). This paper will discuss aspects of: endodontic success and failure;
      the use of leakage studies to assess the quality of the seal; the significance of
      both apical and coronal leakage; followed by a review of the literature.

PMID- 12510476
TI  - The smallpox scenario.

PMID- 12510477
TI  - Sweet as candy, deadly as cigarettes. Teens are flocking to a hip form of smokes.
      There are hidden dangers.

PMID- 12510478
TI  - Cruising for trouble. Don't blame the ocean liners. You can get this stomach bug
      almost anywhere.

PMID- 12510479
TI  - Mammograms for your heart?

PMID- 12510480
TI  - The 'mature worker' glut.

PMID- 12510481
TI  - A plague on the plains.

PMID- 12510482
TI  - Becoming a secret santa.

PMID- 12510483
TI  - A cardinal offense.

PMID- 12510484
TI  - The wound is not healed.

PMID- 12510485
TI  - The end of rule by law. Burned by the scandal of predator priests, Boston's
      Cardinal steps down. His church's problems go on.

PMID- 12510486
TI  - The beluga blues. America's craving for salty, sexy caviar has pushed an ancient
      sea creature to the brink of extinction.

PMID- 12510487
TI  - Why let the dogs out? These vets come to you. House-call and mobile veterinarians
      are reducing stress for pets and owners.

PMID- 12510488
TI  - A smallpox shot? The vaccine works but carries real risks. How to tell if you
      should take it.

PMID- 12510489
TI  - Smallpox shots: make them mandatory. When it comes to epidemic diseases, you
      don't get to decide. The state decides.

PMID- 12510490
TI  - A fall from grace.

PMID- 12510491
TI  - The smallpox conundrum.

PMID- 12510492
TI  - Exercise rights--and wrongs.

PMID- 12510493
TI  - Giving hospitals public report cards.

PMID- 12510494
TI  - Sound and fury. Whale deaths blamed on sonar have triggered a heated debate about
      man-made noise in the sea.

PMID- 12510495
TI  - A humanoid in the manger.

PMID- 12510496
TI  - Marketing to persons with SCI and other disabilities: an untapped population.

PMID- 12510497
TI  - The right to die--ethical dilemmas in persons with spinal cord injury.
AB  - The right to die can be a controversial topic, and health care workers in the
      rehabilitation setting may find themselves in the center of this heated debate.
      This article presents a case study of a patient with tetraplegia, Daniel, and his
      choices regarding life and death. The case study will be examined through the use
      of ethical principles as well as from a legal standpoint. Social, cultural, and
      economic issues are also discussed. Guidelines for possible resolution to the
      conflict are offered.

PMID- 12510498
TI  - Providing SCI education during changing times.
AB  - The educational role of the spinal cord injury (SCI) nurse has changed with the
      ongoing developments in health care. Current statistics show that length of stay
      during both acute care and rehabilitation has shortened dramatically. This fact,
      along with new formats for locating and obtaining educational materials, are a
      few of the challenges that SCI nurses face in providing essential SCI education.
      The Rehabilitation Research and Training Center on Secondary Conditions of SCI,
      and the Model SCI Care Center at the University of Alabama at Birmingham, produce
      a number of accessible and affordable SCI educational materials. These materials
      are available through various electronic formats, including the Internet, e-mail,
      and fax. SCI nurses can use these resources to provide individuals the
      information needed to handle their long-term health care needs following their
      injuries.

PMID- 12510499
TI  - Everybody poops.

PMID- 12510500
TI  - Needle safety technology.

PMID- 12510501
TI  - Data abstraction: designing the tools, recruiting and training the data
      abstractors.
AB  - Data abstraction is very exacting work requiring that data abstractors have both
      knowledge and experience of phenomena being studied. Quality of the data and
      efficiency of the data abstractors are dependent upon the content and design of
      the data abstraction tools. Taking the time to recruit and train qualified data
      abstractors and to develop effective data abstraction tools will result in data
      that not only answers the research question, but also withstands the most
      rigorous critique.

PMID- 12510502
TI  - Converging values: matures, boomers, xers, and nexters in the health care
      workforce.
AB  - The successful leader will try several strategies to bridge the generational gap
      and use the expertise of each cohort group to facilitate patient care. The
      energy, technoliteracy, and commitment to a balance between work and personal
      time by the Generation X and Nexters will complement the wisdom and nursing
      experience of the Mature and Baby Boomer generations. Time must be taken to
      understand the differences between the generations. Recognizing differences and
      appreciating the expertise that everyone brings to the workplace will create an
      environment that embraces generational diversity. Celebrating individual
      differences comes from taking time to learn about coworkers and will enhance a
      healthy work environment.

PMID- 12510503
TI  - Current spasticity management in children with spinal cord injury.

PMID- 12510504
TI  - The graying of nurses and aging in America: a conundrum.

PMID- 12510505
TI  - The nursing shortage: it's already a bumpy ride.

PMID- 12510506
TI  - Aging and spinal cord injury: medical, functional, and psychosocial changes.
AB  - Fifty years ago, people who had a spinal cord injury had very limited life
      expectancies. Today, these individuals can expect to live into their 60s, 70s,
      and beyond. Advances in rehabilitation, technology, surgery, and medicines have
      been chiefly responsible for this change. Recent research in both Europe and the
      United States now indicates that as these people age, they often develop medical
      and functional problems that are not as common in their nondisabled peers until
      much later in life. The importance of these "premature" age-related problems has
      led the National Institute on Disability and Rehabilitation Research to fund the
      Rehabilitation Research and Training Center (RRTC) on Aging With a Spinal Cord
      Injury at Rancho Los Amigos National Rehabilitation Center in Downey, California.
      This article summarizes some of the important findings from this RRTC and from
      other sources.

PMID- 12510507
TI  - An assessment tool for the older person with spinal cord injury.
AB  - Normal aging changes intensify the chronic problems that are experienced by
      individuals with spinal cord injury (SCI). These changes place them at greater
      risk for developing vital systems failure and functional impairments, which if
      unrecognized, may lead to institutionalization or death. Understanding the
      trajectory of aging, and its impact on structure and function, is paramount in
      caring for individuals with SCI. Moreover, trends in health care toward
      capitation, managed care systems, and shifts to outpatient care portend a
      delivery system with more limited resources and greater restrictions (Lubitz,
      Greenberg, Gorina, Wartzman, & Gibson, 2001; National Institute of Aging, 2000).
      These trends potentially compromise health care access, quality, and cost for at
      risk populations, especially for individuals aging with an SCI. Therefore, it
      behooves SCI nurses to develop a comprehensive approach to assess individuals who
      have chronic and debilitating injuries such as SCI. More importantly, assessing
      these individuals will require SCI nurses to adapt current tools that will aid in
      this endeavor and perhaps create new ones that will reflect the magnitude of SCI
      presentations and care. Employing the nursing process, SCI nurses will need to
      gather data from a myriad of sources. The first important step is establishing a
      baseline. Using a functional health pattern tool (FHPT) developed by Gordon
      (1987), and adapted from the North American Nursing Diagnosis Association (1987),
      is one such method of constructing a database and formulating diagnoses (Gordon,
      1994). The FHPT provides a holistic view of individuals and families in any
      practice setting and it can be easily adapted to specialty areas within nursing.
      Therefore its application to both SCI and aging is fitting (Popkess-Vawter,
      1997). These authors adapted the FHPT format to create a tool that will make it
      more reflective of changes that occur in individuals who have SCI and are aging.

PMID- 12510508
TI  - Teaching for life: integrating aging into the rehabilitation education program.
AB  - As the population with spinal cord injury (SCI) steadily ages, nurses find it
      more and more challenging to prevent secondary complications. SCI, an already
      complex topic, is made more so with the addition of the aging process. Aging need
      not be a negative occurrence, but can be viewed as a path in life that requires
      careful navigation along the way. Nurses need to incorporate the concepts of
      wellness and disease prevention education into the initial rehabilitation program
      to better prepare patients for a long and healthy life. This article briefly
      describes respiratory and genitourinary complications associated with aging with
      an SCI and some specific teaching strategies for prevention and management of
      these two complications.

PMID- 12510509
TI  - Making SCI history one year at a time.

PMID- 12510510
TI  - A clinical evaluation of ceiling lifts: lifting and transfer technology for the
      future.

PMID- 12510511
TI  - Increasing your response rate for mail survey data collection.

PMID- 12510512
TI  - Managing stress: an essential of leadership.

PMID- 12510513
TI  - Autonomic dysreflexia in pediatric spinal cord injury.

PMID- 12510514
TI  - The winding road of infertility: the successful path to parenthood with an SCI.

PMID- 12510515
TI  - Strategies for innovative energy-based nursing practice: the Healing Touch
      program.
AB  - The purpose of this article is to share professional knowledge, practice, and
      educational opportunities related to energy-based nursing in order to broaden and
      improve the delivery of health care services. The holistic, theory-based approach
      places a patient's perceived needs first, and cares for the human body as well as
      the spirit. Energy medicine is an intricate part of the patient's expectation for
      health care. Watson's transpersonal-caring-healing model is explored (Watson,
      1999). This model expands the view of the person to one that embodies energy that
      is comprised of spirit, a universal mind, and consciousness. The North American
      Nurses Diagnosis Association (NANDA) recognizes energy therapy as an intervention
      representing a specific theory: human energy field theory (HEFT). This therapy is
      related to the approved nursing diagnosis of energy field disturbance 1.8 (NANDA,
      1995/1996). Healing touch (HT) is an energy-based therapeutic approach to healing
      that emphasizes caring for the whole person based on the HEFT. It is used in the
      nursing profession to influence changes in the human energy system; HT affects
      physical, emotional, mental, and spiritual health. The nursing process is evident
      throughout the curriculum. Nurse researchers report positive patients outcomes.
      The holistic nursing concept of energetic healing returns nurse professionals to
      the essence of nursing. Spinal cord injury (SCI) nurses will benefit by
      increasing their knowledge and awareness of energy therapy to increase patient
      satisfaction and improve outcomes for persons with SCI.

PMID- 12510516
TI  - Pain during spinal cord injury rehabilitation: client perspectives and staff
      attitudes.
AB  - Pain after spinal cord injury (SCI) is well documented in the literature.
      Effective treatment for pain after SCI remains elusive and treatment protocols
      have not been well researched. Staff on a 32-bed SCI rehabilitation unit designed
      and implemented a descriptive research study to improve pain management outcomes.
      An interdisciplinary plan to improve pain management practices was developed as a
      result of the study. Guidelines of the American Academy of Pain Medicine and the
      American Pain Society (1997) and the Agency for Healthcare Policy and Research
      (1992 [now called Agency for Healthcare Research and Quality]) provided the
      framework for the interdisciplinary management of pain.

PMID- 12510517
TI  - Planting a vision firmly in the ground.

PMID- 12510518
TI  - Ethical considerations in nursing research.

PMID- 12510519
TI  - Men in nursing: a different voice and a different brain.

PMID- 12510520
TI  - Animal-assisted therapy: a modality of treatment for the patient with spinal cord
      injury.

PMID- 12510522
TI  - [Central sterilization clinical nurse. Interview by Eric Charles].

PMID- 12510523
TI  - [And if we revisit the evolution of the profession...].

PMID- 12510524
TI  - [Economic impact of the physician/nurse substitution in community health care
      sector].

PMID- 12510525
TI  - [Professional evolution of nurses].

PMID- 12510526
TI  - ["We must accept the idea of a future shortage of physicians"].

PMID- 12510527
TI  - [Developing a compliance consultation for HIV/AIDS treatments. From theory to
      practice].

PMID- 12510528
TI  - [Diabetes and cardiovascular disease: a key role for the state diploma nurses].

PMID- 12510529
TI  - [Nursing care and gastrointestinal stomas].

PMID- 12510530
TI  - [Management of pain: documentation in the nursing record].

PMID- 12510531
TI  - [Clowns in hospitals or the wonderful story of a successful collaboration].

PMID- 12510532
TI  - [Esthetic surgical procedures].

PMID- 12510533
TI  - [Extended release oxycodone. An oral opioid analgesic for cancer patients with
      chronic pain].

PMID- 12510534
TI  - [Diabetic diet for children].

PMID- 12510535
TI  - [Causes of decubitus ulcers].

PMID- 12510536
TI  - How to stay stuck in the wrong career.
AB  - Everyone knows a story about a talented business person who has lost his passion
      for work, or a person who ditched a 20-year career to pursue something completely
      different and is the happier for it. "Am I doing what is right for me, or should
      I change direction?" is one of the most pressing questions for today's midcareer
      professional. A true change of direction is hard to swing. Many academics and
      career counselors contend that the problem lies in basic human behavior: We fear
      change and don't want to make sacrifices. But author Herminia Ibarra suggests
      another explanation. People most often fail, she says, because they take the
      wrong approach to finding new careers. Indeed, the conventional wisdom on how to
      change careers is a prescription for how to stay put. Most of us have heard that
      the key to a successful career change is figuring out what we want to do next,
      then acting on that knowledge. But change actually happens the other way around.
      Doing comes first, knowing second, because changing careers means redefining our
      working identity--our sense of self in our professional roles, what we convey
      about ourselves to others and, ultimately, how we live our working lives. Who we
      are and what we do are tightly connected, the result of years of action. And to
      change that connection, we must first resort to action--exactly what the
      conventional wisdom cautions us against. Many successful career changers use a
      test-and-learn model of change, putting their possible identities into practice
      and then working and crafting them until the identities are sufficiently grounded
      in experience to guide more decisive steps. To make a break with the past, we
      must venture into the unknown.

PMID- 12510537
TI  - What's a business for?
AB  - In the wake of the recent corporate scandals, it's time to reconsider the
      assumptions underlying American-style stock-market capitalism. That heady
      doctrine--in which the market is king, success is measured in terms of
      shareholder value, and profits are an end in themselves--enraptured America for a
      generation, spread to Britain during the 1980s, and recently began to gain
      acceptance in Continental Europe. But now, many wonder if the American model is
      corrupt. The American scandals are not just a matter of dubious personal ethics
      or of rogue companies fudging the odd billion. And the cure for the problems will
      not come solely from tougher regulations. We must also ask more fundamental
      questions: Whom and what is a business for? And are traditional ownership and
      governance structures suited to the knowledge economy? According to corporate
      law, a company's financiers are its owners, and employees are treated as property
      and recorded as costs. But while that may have been true in the early days of
      industry, it does not reflect today's reality. Now a company's assets are
      increasingly found in the employees who contribute their time and talents rather
      than in the stockholders who temporarily contribute their money. The language and
      measures of business must be reversed. In a knowledge economy, a good business is
      a community with a purpose, not a piece of property. If, like many European
      companies, a business considers itself a wealth-creating community consisting of
      members who have certain rights, those members will be more likely to treat one
      another as valued partners and take responsibility for telling the truth. Such a
      community can also help repair the image of business by insisting that its
      purpose is not just to make a profit but to make a profit in order to do
      something better.

PMID- 12510538
TI  - The competitive advantage of corporate philanthropy.
AB  - When it comes to philanthropy, executives increasingly see themselves as caught
      between critics demanding ever higher levels of "corporate social responsibility"
      and investors applying pressure to maximize short-term profits. In response, many
      companies have sought to make their giving more strategic, but what passes for
      strategic philanthropy is almost never truly strategic, and often isn't
      particularly effective as philanthropy. Increasingly, philanthropy is used as a
      form of public relations or advertising, promoting a company's image through high
      profile sponsorships. But there is a more truly strategic way to think about
      philanthropy. Corporations can use their charitable efforts to improve their
      competitive context--the quality of the business environment in the locations
      where they operate. Using philanthropy to enhance competitive context aligns
      social and economic goals and improves a company's long-term business prospects.
      Addressing context enables a company to not only give money but also leverage its
      capabilities and relationships in support of charitable causes. The produces
      social benefits far exceeding those provided by individual donors, foundations,
      or even governments. Taking this new direction requires fundamental changes in
      the way companies approach their contribution programs. For example,
      philanthropic investments can improve education and local quality of life in ways
      that will benefit the company. Such investments can also improve the company's
      competitiveness by contributing to expanding the local market and helping to
      reduce corruption in the local business environment. Adopting a context-focused
      approach goes against the grain of current philanthropic practice, and it
      requires a far more disciplined approach than is prevalent today. But it can make
      a company's philanthropic activities far more effective.

PMID- 12510539
TI  - Holes at the top. Why CEO firings backfire.
AB  - When a company does well, its CEO is showered with money and adulation. When it
      does poorly, the CEO gets the blame--and the boot. For better or worse, investors
      now view chief executives as the primary determinant of corporate performance.
      But the reality is that most companies perform no better after they dismiss their
      CEOs than they did in the years leading up to the dismissals. Worse, the
      organizational disruption created by a rushed firing can leave a company with
      deep and lasting scars. Far from being a silver bullet, the replacement of a CEO
      often amounts to little more than a self-inflicted wound. The blame for such poor
      results, the author argues, lies squarely with boards of directors. Boards often
      lack the strategic understanding of the business necessary to give due diligence
      to choosing a replacement CEO. Concern over restoring investor confidence quickly
      -rather than doing what's right for the company--drives the selection process.
      And all too often, companies continue to be dogged by the same old problems after
      the new CEOs come on board. But a good board can make a CEO replacement pay off
      if its members first develop a better understanding of the business context,
      worry less about pleasing the investment community and more about a replacement's
      strategic fit, and take an active role in overseeing the new CEO and the
      performance and direction of the company. In the long run, such approaches are
      likely to foster stability at the helm--making it less likely a company will have
      to fire its CEO in the first place.

PMID- 12510540
TI  - The young and the clueless.
AB  - It's natural to promote your best and brightest, especially when you think they
      may leave for greener pastures if you don't continually offer them new challenges
      and rewards. But promoting smart, ambitious young managers too quickly often robs
      them of the chance to develop the emotional competencies that come with time and
      experience--competencies like the ability to negotiate with peers, regulate
      emotions in times of crisis, and win support for change. Indeed, at some point in
      a manager's career--usually at the vice president level--raw talent and ambition
      become less important than the ability to influence and persuade, and that's the
      point at which the emotionally immature manager will lose his effectiveness. This
      article argues that delaying a promotion can sometimes be the best thing a senior
      executive can do for a junior manager. The inexperienced manager who is given
      time to develop his emotional competencies may be better prepared for the
      interpersonal demands of top-level leadership. The authors recommend that senior
      executives employ these strategies to help boost their proteges' people skills:
      sharpen the 360-degree feedback process, give managers cross-functional
      assignments to improve their negotiation skills, make the development of
      emotional competencies mandatory, make emotional competencies a performance
      measure, and encourage managers to develop informal learning partnerships with
      peers and mentors. Delaying a promotion can be difficult given the steadfast
      ambitions of many junior executives and the hectic pace of organizational life.
      It may mean going against the norm of promoting people almost exclusively on
      smarts and business results. It may also mean contending with the disappointment
      of an esteemed subordinate. But taking the time to build people's emotional
      competencies isn't an extravagance; it's critical to developing effective
      leaders.

PMID- 12510541
TI  - Expensing options solves nothing.
AB  - The use of stock options for executive compensation has become a lightning rod
      for public anger, and it's easy to see why. Many top executives grew hugely rich
      on the back of the gains they made on their options, profits they've been able to
      keep even as the value they were supposed to create disappeared. The supposed
      scam works like this: Current accounting regulations let companies ignore the
      cost of option grants on their income statements, so they can award valuable
      option packages without affecting reported earnings. Not charging the cost of the
      grants supposedly leads to overstated earnings, which purportedly translate into
      unrealistically high share prices, permitting top executives to realize big gains
      when they exercise their options. If an accounting anomaly is the problem, then
      the solution seems obvious: Write off executive share options against the current
      year's revenues. The trouble is, Sahlman writes, expensing option grants won't
      give us a more accurate view of earnings, won't add any information not already
      included in the financial statements, and won't even lead to equal treatment of
      different forms of executive pay. Far worse, expensing evades the real issue,
      which is whether compensation (options and other-wise) does what it's supposed to
      do--namely, help a company recruit, retain, and provide the right people with
      appropriate performance incentives. Any performance-based compensation system has
      the potential to encourage cheating. Only ethical management, sensible
      governance, adequate internal control systems, and comprehensive disclosure will
      save the investor from disaster. If, Sahlman warns, we pass laws that require the
      expensing of options, thinking that's fixed the fundamental flaws in corporate
      America's accounting, we will have missed a golden opportunity to focus on the
      much more extensive defects in the present system.

PMID- 12510542
TI  - Crisis communication. Lessons from 9/11.
AB  - The sheer enormity of last year's terrorist attacks on the World Trade Center and
      the Pentagon gave new meaning to the term "crisis management." Suddenly,
      companies near Ground Zero, as well as those more than a thousand miles away,
      needed a plan. Because the disasters disrupted established channels not only
      between businesses and customers but between businesses and employees, internal
      crisis-communications strategies that could be quickly implemented became a key
      responsibility of top management. Without these strategies, employees' trauma and
      confusion might have immobilized their firms and set their customers adrift. In
      this article, executives from a range of industries talk about how their
      companies, including Morgan Stanley, Oppenheimer Funds, American Airlines,
      Verizon, the New York Times, Dell, and Starbucks, went about restoring operations
      and morale. From his interviews with these individuals, author and management
      professor Paul Argenti was able to distill a number of lessons, each of which, he
      says, may "serve as guideposts for any company facing a crisis that undermines
      its employees' composure, confidence, or concentration." His advice to senior
      executives includes: Maintain high levels of visibility, so that employees are
      certain of top management's command of the situation and concern; establish
      contingency communication channels and work sites; strive to keep employees
      focused on the business itself, because a sense of usefulness enhances morale and
      good morale enhances usefulness; and ensure that employees have absorbed the
      firm's values, which will guide them as they cope with the unpredictable. The
      most forward-thinking leaders realize that managing a crisis-communications
      program requires the same dedication and resources they give to other dimensions
      of their business. More important, they realize that their employees always come
      first.

PMID- 12510543
TI  - Why entrepreneurs don't scale.
AB  - It's well known that many executives who excel at starting businesses or projects
      fizzle out--in other words, they fail to "scale"--as their ventures grow. But the
      reasons have remained fuzzy. In this article, leadership coach John Hamm
      identifies four management tendencies that work for small-company or business
      unit leaders but become Achilles' heels as those individuals try to run larger
      organizations. The first tendency is loyalty to comrades. In entrepreneurial
      mode, you need to lead as though you're in charge of a combat unit on the wrong
      side of enemy lines. But blind loyalty can become a liability in managing a
      complex organization. The second tendency, task orientation, is critical in
      driving toward a big product launch, but excessive attention to detail can cause
      a large organization to lose sight of its long-term goals. The third tendency,
      single-mindedness, is important in a visionary unleashing a revolutionary product
      or service on the world but can limit the company's potential as it grows. And
      the fourth tendency, working in isolation, is fine for the brilliant scientist
      focused on an ingenious idea. But it's disastrous for a leader whose expanding
      organization increasingly relies on many other people. Leaders who scale deal
      honestly with problems and quickly weed out nonperformers. They see past
      distractions and establish strategic priorities. They learn how to deal
      effectively with diverse employees, customers, and external constituencies. And,
      most important, they make the company's continuing health and welfare their top
      concern.

PMID- 12510544
TI  - Prostanoids in the treatment of intermittent claudication--a meta-analysis.
AB  - BACKGROUND: Numerous studies have established the efficacy of prostanoids in PAD
      stages III and IV, but the role of prostanoids as an alternative or additive
      treatment in patients suffering from PAD II is less clear. To resolve this
      uncertainty we performed a meta-analysis of all randomised controlled studies
      analysing effects of prostanoids in patients suffering from intermittent
      claudication. METHODS: 96 studies have been screened by computerised searches of
      MEDLINE and EMBASE. Relevant studies were pooled in Cochrane's Review-manager
      4.1. RESULTS: 19 studies were included for further analysis. Five studies could
      not be pooled for analysing walking distances, because standard deviations were
      not stated. Eight studies compared effects of any prostanoid i.v. vs. placebo. In
      total 557 patients (281/276) were included for analysis of painfree--walking
      distance (PFWD) and 519 patients (262/257) for analysis of maximum walking
      distance (MWD). Prostanoids compared to placebo significantly improved mean PFWD
      by 28% (7%-49%, P = 0.008) and mean MWD by 30% (11%-50%, P = 0.002). At least one
      adverse reaction was reported from 39.6% of the patients treated with
      prostacyclin and its analogues and from 13.7% of the patients treated with
      prostaglandin E1. CONCLUSION: Patients suffering from intermittent claudication
      benefit from administration of prostaglandin E1 by a significant improvement of
      their walking capacity.

PMID- 12510545
TI  - [The role of perforating vein dissection in the treatment concept of venous
      ulcers--myths and evidence].
AB  - Crural ulcers represent the most serious form of chronic venous incompetence
      (CVI). According to duplex studies superficial venous incompetence predominate in
      this stage of the disease, but combined refluxes of superficial and deep veins
      are also common. Despite a positive correlation between the number of incompetent
      perforators and the stage of CVI isolated incompetence of perforating veins in
      venous ulcers are rarely found. Additionally, only a minority of incompetent
      perforators depict larger reflux volumes. Therefore, doubts about a causal role
      of perforators incompetence in ulcer genesis are justified. According to
      phlebodynamometric studies the risk of crural ulcer development increases with
      the degree of hemodynamic compromise. Ulcer healing can only be achieved after
      complete normalization of ambulatory venous hypertension. In case of superficial
      refluxes and concomitant incompetence of perforating veins exclusion of the
      superficial component is sufficient to achieve this goal. Incompetent perforators
      normalize their function consecutively. In contrast, venous hypertension persists
      after exclusion of superficial refluxes in case of incompetent perforators and
      irreversible damage of the deep venous system. Surgical therapy studies exactly
      reflect the results of these hemodynamic examinations. Therefore, the role of
      endoscopic subfascial perforator dissection (ESPD) in the treatment of venous
      ulcers remains unclear. Future therapy studies should take into account that the
      definite role of ESPD in ulcer healing can only be examined without additional
      treatment of refluxes in the saphena system. Additionally, all study patients
      should be classified according to the CEAP nomenclature and Hach's classification
      of chronic compartment syndrome. Methodological differences in technique and
      extent of ESPD have also to be taken into account.

PMID- 12510546
TI  - Functional analysis of retinal vessel diameter reaction to artificially raised
      intraocular pressure in glaucoma patients with and without dorzolamide therapy.
AB  - BACKGROUND: Examination of the influence of dorzolamide on the autoregulation of
      retinal vessel diameter in glaucoma patients. PATIENTS AND METHODS: Eleven
      patients with primary open angle glaucoma (age 60 +/- 11) without medication and
      four weeks after starting therapy with dorzolamid eye drops three times daily
      were examined in the study. Short-time rise of intraocular pressure (IOP) was
      obtained via suction-cup. Functional reaction of the diameter of a segment of a
      retinal artery and corresponding vein were assessed by retinal vessel analyzer.
      RESULTS: Dorzolamid lowered the IOP from 23.3 +/- 1.3 to 17.6 +/- 2.2 mmHg (p =
      0.004). Therapy did not influence the absolute diameter of retinal vessels
      regarding maximal dilatation caused by the pressure rising provocation. In eyes
      with treatment the diameter decreased faster to baseline values (arteries 100
      sec, veins 220 sec) compared to those without treatment (arteries 350 sec, veins
      480 sec). CONCLUSION: Dorzolamid might possibly be able to accelerate
      autoregulation of retinal vessels in response to short term artificial IOP
      increase.

PMID- 12510547
TI  - Magnetic resonance phase contrast velocity measurement for non-invasive follow up
      after percutaneous transluminal angioplasty.
AB  - BACKGROUND: The aim of this study was to evaluate magnetic resonance phase
      contrast velocimetry (MRVL) as a non-invasive follow up tool to assess restenosis
      after percutaneous transluminal angioplasty (PTA). PATIENTS AND METHODS: We
      prospectively investigated 51 consecutive patients who underwent PTA of the
      femoropopliteal region. MRVL was conducted prior, one day, six weeks, twelve
      weeks and 24 weeks after PTA using a circular polarized extremity coil and a
      gradient echo sequence (TR/TE 600/6 ms, flip angel 30 degrees, slice thickness 10
      mm). Hemodynamic data, derived from the MR phase contrast sequence, allowed to
      calculate the degree of area stenosis of the lesion treated with PTA. These data
      were correlated with clinical hemodynamic parameters (ankle-brachial index and
      walking distance). RESULTS: The mean grade of area stenosis was 69% +/- 27%
      before PTA, 30% +/- 20% one day, 29% +/- 23% six weeks, 39% +/- 17% twelve weeks
      and 42% +/- 18% 24 weeks after PTA and correlated well with clinical data and the
      post angioplasty clinical course of the patients. CONCLUSIONS: Follow up
      measurements using MRVL are suitable to assess restenosis after PTA and allow
      quantifying the grade of recurrent stenosis as well as the hemodynamic
      consequences.

PMID- 12510548
TI  - getABI: German epidemiological trial on ankle brachial index for elderly patients
      in family practice to dedect peripheral arterial disease, significant marker for
      high mortality.
AB  - BACKGROUND: Peripheral arterial occlusive disease (PAD) is a common, but widely
      underestimated disease associated with a high morbidity and mortality risk. PAD
      can be regarded as an indicator for a generalized atherothrombosis. In view of
      the scarcity of appropriate representative data from Germany, we set up a large
      scale epidemiological prospective observational study. PATIENTS AND METHODS: The
      primary objectives of the study comprise the estimation of the actual prevalence
      of PAD in unselected elderly patients, the determination of the risk factor
      profile of these patients, the incidence of the disease, as well as the relative
      risk of death due to any cause or cardiovascular, cerebrovascular or vascular
      events, respectively, of PAD patients compared to those without PAD, in
      representative primary health care settings. In addition, awareness of the
      problem of the disease PAD and its implications on the part of the treating
      physicians is determined by a Physician Awareness Questionnaire. RESULTS: After
      having been trained by 34 centers of excellence (angiologists), 344 general
      practitioners have recruited 6880 patients aged 65 years or older and will follow
      them up over 3 years. Key examinations include bilateral Doppler sonographic
      measurements and determination of the ankle brachial index (ABI) under
      standardized conditions during rest and exercise, laboratory evaluations at
      baseline including homocysteine, physical examinations, and the WHO Rose
      questionnaire. The study is purely observational and no interventions are planned
      or stipulated. CONCLUSIONS: The getABI cohort is an important contribution to the
      widely neglected research area in general practice in Germany. Data from research
      in general practice represent the foundation for medical decision making in the
      sense of evidence based medicine.

PMID- 12510549
TI  - Peripheral arterial disease in diabetes mellitus type 1 and type 2: are there
      different risk factors?
AB  - BACKGROUND: Diabetic patients have increased prevalence of peripheral arterial
      disease (PAD). It is not clearly shown whether the prognostic factors are
      identical in relation to the type of diabetes. This study was done to compare the
      associations of PAD with risk factors and with micro- and macrovascular
      complications of inpatients with type 1 and type 2 diabetes. METHODS: In a
      retrospective cross-sectional study 1087 patients with type 1 diabetes and 1060
      patients with type 2 diabetes were examined. PAD was diagnosed when ankle
      brachial-pressure-index (ABI) was < 1.0. In cases with incompressible arteries
      (mediasclerosis) pulse wave forms were analyzed. Multivariate logistic regression
      analysis was applied to evaluate the impact of different variables on PAD risk,
      after adjusting for different variables separately. RESULTS: In both types of
      diabetes (type 1 vs. type 2) PAD risk (odds ratio; OR) was increased in the
      presence of coronary heart disease (OR 9.3 vs. 3.5), diabetic nephropathy (OR 3.0
      vs. 2.8), neuropathy (OR 7.9 vs. 1.8), foot ulceration (OR 8.9 vs. 5.5),
      increased daily insulin requirement > 0.6 mu/kg b.w. (OR 5.2 vs. 2.9), diabetes
      duration of 20-29 years (OR 28.9) and > 30 years (OR 51.1) in type 1 diabetes,
      and diabetes duration of 10-19 years (OR 3.8) and > 20 years (OR 4.3) in type 2
      diabetes. In type 2 diabetes, PAD risk was associated with microalbuminuria (OR
      2.1), macroalbuminuria (OR 3.3), background retinopathy (OR 1.9), proliferative
      retinopathy (OR 2.8), increased triglycerides (TG) (OR 1.7) and decreased HDL
      cholesterol (HDL-C > 0.90 mmol/l: OR 0.49). CONCLUSIONS: PAD risk factors and
      micro- and macrovascular comorbidity are very similar in type 1 and type 2
      diabetes.

PMID- 12510550
TI  - Value of transesophageal echocardiography, esophago-gastroduodenoscopy and
      retinoscopy prior to intra-arterial fibrinolytic therapy in patients with
      peripheral arterial disease.
AB  - BACKGROUND: We prospectively investigated the need for esophagogastroduodenoscopy
      (EGD), transesophageal echocardiography (TEE) and retinoscopy for pre
      interventional screening in patients with peripheral arterial occlusive disease
      (PAD) prior to intraarterial fibrinolytic therapy. PATIENTS AND METHODS: 212
      consecutive patients suffering from PAD (164 male and 48 female, mean age: 64 +/-
      11 years, 161 patients stage II of Fontaine's classification, 10 patients at
      stage III and 41 patients at stage IV) referred for interventional treatment were
      included. 173 EGDs, 169 TEEs and 188 retinoscopies were performed within one week
      prior to fibrinolysis. 114 patients had all three examinations. RESULTS:
      Pathologic findings were detected in 56 (49%) of the 114 patients: 23 erosions,
      12 ulcers, 2 esophagites, 1 gastric carcinomata, 3 intracardiac thrombi, 5 aortic
      thrombi, 11 diabetic and 5 hypertensive retinopathies and 1 with retinal
      aneurysms. 30 patients (25%) received fibrinolytic therapy, despite a
      contraindication: The one patient with ventricular thrombus was treated as an
      ultimate therapy, and amputation was prevented. Two patients showing plaques
      covered by large thrombi in the descending thoracic aorta were treated because
      cranial embolism should not occur. Four diabetic patients with multilevel
      disease, severe claudication and prior retinal bleeding were treated.
      Fibrinolytic therapy was started on 23 patients after complete healing of the
      mucosal lesions. CONCLUSION: TEE revealed potential sources of embolization in 4%
      of the patients and is justified to reduce the individual risk. Retinoscopy
      should be done in patients with diabetes mellitus and hypertension, and if prior
      bleeding is present fibrinolysis should be done only if other treatment-regimes
      are not available.

PMID- 12510551
TI  - Thrombophlebitis associated with intravenous injection anaesthetics: influence of
      arm positioning.
AB  - BACKGROUND: Thrombophlebitis (TP) is a frequent complication of the intravenous
      application of injection anaesthetics. We investigated the influence of different
      arm positions on the incidence of such a complication in patients undergoing
      shoulder arthroscopy. PATIENTS AND METHODS: This prospective, randomised study
      was done in 86 consecutive major shoulder arthroscopies. In order to evaluate the
      influence of different arm positions, the arm not operated on was positioned
      either cranial (n = 31) or caudal (n = 55) to the level of the right atrium. The
      number of TP in the 5 days following the arthroscopy was detected clinically and
      proven by ultrasound studies. RESULTS: 8 TP occurred in the group of patients
      with caudal arm positioning and none in the other group. Statistically, the
      incidence of TP was not associated with the weight or the height of the patients
      nor with the duration of the anaesthesia or the doses of anaesthetics used in
      each patient (p < 0.05). CONCLUSION: An elevated position of the arm used for
      anaesthesia during shoulder arthroscopy is suggested in order to prevent TP.

PMID- 12510552
TI  - Predictors of mortality in patients undergoing surgery for ruptured aortic
      aneurysm.
AB  - BACKGROUND: A study was designed to determine significant variables that could be
      used to predict survival in patients with ruptured abdominal aortic aneurysm.
      PATIENTS AND METHODS: Data of 106 unselected consecutive patients with ruptured
      abdominal aortic aneurysm undergoing operation between 1989 and 1998 were
      identified from a prospective hospital-based registry. A total of 32 variables
      were analyzed including demographic characteristics, vascular risk factors,
      coexisting conditions, preoperative findings, intraoperative variables, and
      postoperative complications. Preoperative and intraoperative variables related to
      vital status (alive, death) in the univariate analysis were subjected to stepwise
      linear regression analysis to determine whether a combination of variables would
      predict death. Of 99 evaluable patients, 48 died (mortality rate 48.5%). RESULTS:
      At univariate analysis, age, serum creatinine, hemoglobin, electrocardiographic
      ischemia, loss of consciousness on admission, preoperative shock, supra-renal
      rupture, and transfusion requirements were significantly associated with 30-day
      operative mortality. Postoperative complications except sepsis, mesenteric
      ischemia, and neurologic events were significantly associated with mortality.
      Electrocardiographic ischemia, shock, and supra-renal rupture appeared to be
      independent predictors of mortality in the multivariate analysis. The cumulative
      effect of 0, 1, and > or = 2 risk factors on mortality was 29%, 39%, and 90%,
      respectively. CONCLUSIONS: Electrocardiographic ischemia, preoperative shock, and
      supra-renal rupture were predictors of death in patients with ruptured abdominal
      aortic aneurysm.

PMID- 12510553
TI  - Epithelioid angiosarcoma of the aorta.
AB  - Primary malignant tumors of the aorta are extremely rare. Review of the
      literature indicates that there are nearly 100 recorded cases of primary
      malignant tumors of the aorta. The purpose of this article is to present an
      additional case of the primary malignant tumors of the aorta which initially has
      been misinterpretated as atherosclerosic disease. This aortic tumor was of
      endothelial origin and immunohistochemical studies classified the tumor as an
      epithelioid angiosarcoma. The treatment resulted in an abdominal aortic repair.
      MRI of the spine revealed multifocal metastatic disease of the axial skeleton and
      a subsequent chemotherapy was performed. The patient died 17 months after the
      initial diagnosis.

PMID- 12510554
TI  - Digital arterial occlusive disease and parvovirus B19 infection.
AB  - We report a case of a 37-year-old white woman, who presented with digital
      arterial occlusions associated with parvovirus B19 infection. Two other member of
      the family presented acute febrile illness, polyarthralgia (husband), and
      erythema infectiosum (son) during the same month. This new report gives weight to
      the concept that acute human parvovirus infection could become part of the
      differential diagnosis of acute digital occlusive arteriopathy.

PMID- 12510555
TI  - Recurrent isolated calf muscle thrombosis due to a venous aneurysm of the soleal
      muscle veins.
AB  - A rare case of venous aneurysm involving the soleal muscle vein in an 18-year-old
      woman is presented. The patients showed three episodes of ultrasonographically
      proven calf muscle thrombosis within 2 years. After a short course of low
      molecular-weight heparin at a therapeutic dosage, complete thrombus
      recanalization was achieved. To prevent further thrombotic episodes, surgery
      including ligation and resection of the aneurysm was performed. At the 3-month
      follow-up study the patient had completely recovered.

PMID- 12510556
TI  - Local treatment of dry gangrene.

PMID- 12510557
TI  - [Aneurysms from the viewpoint of medical history].
AB  - The history of arterial aneurysms dates back to the old Egypts, Byzantines and
      Greeks. Vesal 1557 and Harvey 1628 introduced the disease into modern medicine.
      They diagnosed a pulsating tumor intra vitam and confirmed the aneurysm at
      autopsy. Further corner stones during the 18th and beginning of the 19th century
      were the monographs of Lancisi and Scarpa, the latter beautifully illustrated.
      The first effectful therapy was external compression, the second ligature of the
      artery proximal to the aneurysm, which was pioneered by John Hunter in 1785.
      Endoaneurysmoraphy (Matas) and wrapping by cellophane were performed, before
      diagnostic ultrasound and bypass surgery became routine procedures and improved
      dramatically the survival of the patients. The diagnostic and therapeutic
      problems in the middle of the 20th century are illustrated by the fate of two
      prominent patients, Albert Einstein and Thomas Mann, who died both of a ruptured
      aneurysm in 1955.

PMID- 12510558
TI  - Haunted by Enron's ghost. National Century Financial Enterprises files for
      Chapter 11, leaving a string of broken healthcare chains and hospitals.
AB  - Some are calling it the Enron of the healthcare industry. Ryder trucks hauled
      possible evidence from embattled financier National Century Financial Enterprises
      during an FBI raid. NCFE filed for Chapter 11 bankruptcy protection last week,
      sending ripples through the industry and contributing to the bankruptcies of a
      string of national healthcare chains and at least six hospitals.

PMID- 12510559
TI  - Panel offers ways to ease burdens of compliance.

PMID- 12510560
TI  - Ailing system. IOM report, new policies to spur healthcare reform.

PMID- 12510561
TI  - Calling off the wedding. Long-planned merger falls through in New York.

PMID- 12510562
TI  - Verify, but please, only once. Physician credentialing is important, but too many
      are doing too much of it.

PMID- 12510563
TI  - Web survey. October results: 'Is healthcare a scary experience?'.

PMID- 12510564
TI  - Access denied. Mayo Clinic is a believer in using biometrics to protect medical
      data, but technological flaws shut doctors out, shut system down.

PMID- 12510565
TI  - Eyeing a new solution. Next generation of scanners offers security advances.

PMID- 12510566
TI  - Straight talk: new approaches in healthcare. Are you in denial over your denials?
      Enhance your revenues with denial management.
AB  - Most health systems lose between 3% and 5% of net revenues as a result of payment
      denials from insurance companies. But it doesn't have to be that way. In the
      eighth installment of Straight Talk, we talk about the steps necessary to recover
      lost revenue through a denial-management program, which involves an investment in
      information technology and a commitment to business-process change. Denial
      management isn't just the responsibility of the employees in patient financial
      services--it's everyone's responsibility at the hospital. Modern Healthcare and
      PricewaterhouseCoopers present Straight Talk. The session on denial management
      was held at Modern Healthcare's Chicago headquarters on November 6, 2002. Charles
      S. Lauer, Publisher of Modern Healthcare, was the moderator.

PMID- 12510567
TI  - Placing a bet on biotech.

PMID- 12510568
TI  - New Jersey Medicine's story of the year 2002. The professional liability
      insurance crisis.

PMID- 12510569
TI  - Contraindicated antiretroviral drug combinations.

PMID- 12510570
TI  - Birth defects surveillance.
AB  - Birth defects are identified at the time of delivery in approximately one out of
      thirty-three babies. Birth defect surveillance has become a very important public
      health tool for tracking rates and trends in the prevalence of these
      abnormalities and is useful in establishing risk factors and potential
      etiologies.

PMID- 12510571
TI  - Syringe exchange proposal.

PMID- 12510572
TI  - Assessing and treating depressed Latino patients in primary care.
AB  - There are an increasing number of monolingual Spanish-speaking patients in New
      Jersey. This paper addresses the essential issues in recognizing and treating
      depression in Latino patients in a primary care setting.

PMID- 12510573
TI  - Does someone have to die?

PMID- 12510574
TI  - Malpractice losses in obstetrics.

PMID- 12510575
TI  - Why nurses leave their profession.

PMID- 12510576
TI  - Heavy metals in dredged sediment-derived soils along the rivers Scheldt and Leie:
      geographical distribution, bioavailability and ecosystem effects.

PMID- 12510577
TI  - Use of steady state oxygen profiles to estimate degradation rates of a diesel
      contamination in a loamy sand soil.

PMID- 12510578
TI  - Participatory agro-ecological characterisation in Syria.

PMID- 12510579
TI  - Computational fluid dynamics in wastewater treatment.

PMID- 12510580
TI  - Data-based mechanistic modelling of the fast dynamic plant response to sudden
      changes in microclimate.

PMID- 12510581
TI  - Temperature and pressure inactivation of tomato pectinases: a kinetic study.

PMID- 12510582
TI  - Angiotensin-I Converting Enzyme (ACE) inhibitory peptides derived from pea and
      whey protein.

PMID- 12510583
TI  - Multiple alignment of sequences and structures.

PMID- 12510584
TI  - The Rhizobium etli calcium-binding protein alsymin has calmodulin-like
      properties.

PMID- 12510585
TI  - Relationship between intra- and extracellular dextran dextrinase from
      Gluconobacter oxydans ATCC 11894.

PMID- 12510586
TI  - [Comparative genetics and evolutionary morphology of symbiosis formed by plants
      with nitrogen-fixing microbes and endomycorrhizal fungi].
AB  - Results of comparative morphological and genetic analyses are described for two
      major plant-microbe endosymbioses: N2-fixing nodules (with rhizobia or
      actinomycetes Frankia) and arbuscular mycorrhiza (with Glomales fungi).
      Development from the primordia formed de novo in root tissues is common for all
      known types of N2-fixing nodules. However, their structure varies greatly with
      respect to: (i) tissue topology (location of vascular bundles is peripheral in
      legumes but central in non-legumes); (ii) position of nodule primordium (inner or
      outer cortex in legumes, whereas pericycle in non-legumes); (iii) stability of
      apical meristem (persistent in the indeterminate nodules, transient in the
      determinate ones). In addition, legumes vary in ability to form compartments
      harboring endosymbiotic rhizobia that can be located intercellularly (infection
      threads) and intracellularly (symbiosomes). Using pea (Pisum sativum) symbiotic
      mutants, the nodule developmental program is dissected into a range of spatially
      and temporarily differentiated steps composing four sub-programs (development of
      endosymbiotic compartments; nodule histogenesis; autoregulation of nodulation;
      bacteroid differentiation). The developmental mutations are suggested in some
      cases to reverse the endosymbiotic system into the morphologically simpler forms
      some of which may correspond to the ancestral stages of nodule evolution.
      Origination of legume-rhizobial and actinorhizal symbioses is suggested to be
      based on a set of preadaptations many of which had been evolved in angiosperms
      during coevolution with arbuscular mycorrhizal fungi (e.g. inter- and
      intracellular maintenance of symbionts, their control via defence-like reactions
      and recognition of chitin-like molecules). Analysis of parallel morphological
      variation in symbiotic mutants and wild-growing legume species enables us to
      reconstruct the major stages of evolution for N2-fixing symbioses. This evolution
      proceeded to a sufficient degree independently from the basic physiological
      function of nodules (symbiotic N2-fixation) and possibly a recruiting of plant
      genes that initially fulfilled various "non-symbiotic" functions into the genetic
      networks monitoring plant-microbe interactions.

PMID- 12510587
TI  - [Principles and methods of geometric morphometrics].
AB  - The basic concepts, notions and methods of geometric morphometrics (GM) are
      considered. This approach implies multivariate analysis of landmark coordinates
      located following certain rules on the surface of a morphological object. The aim
      of GM is to reveal differences between morphological objects by their shapes as
      such, the "size factor" being excluded. The GM is based on the concept of
      Kendall's space (KS) defined as a hypersphere with points distributed on its
      surface. These points are the shapes defined as aligned landmark configurations.
      KS is a non-Euclidian space, its metrics called Procrustes is defined by landmark
      configuration of a reference shape relative to which other shapes are aligned and
      compared. The differences among shapes are measured as Procrustes distances
      between respective points. For the linear methods of multivariate statistics to
      be applied to comparison of shapes, the respective points are projected onto the
      tangent plane (tangent space), the tangent point being defined by the reference.
      There are two principal methods of shape comparisons in GM: the Procrustes
      superimposition (a version of the least squares analysis) and thin-plate spline
      analysis. In the first case, Procrustes residuals are the outcome shape variables
      which remain after isometric alignment of the shapes being compared. Their
      summation over all landmarks yields Procrustes distances among these shapes. The
      Procrustes distances can be used in multivariate analyses just as the Euclidian
      distances. In the second case, the shapes are fitted to the references by
      stretching/compressing and shearing until complete identity of their landmark
      configurations. Eigenvectors of resulting bending energy matrix are defined as
      new shape variables, principal warps which yield another shape space with the
      origin defined by the reference. Projections of the shapes being compared onto
      principal warps yield partial warps, and their covariance matrix decomposition
      into eigenvectors yields relative warps which are similar to principal components
      (in particular, they are mutually orthogonal). Both partial and relative warps
      can be used in many multivariate statistic analyses as quantitative shape
      variables. Results of thin-plate spline analysis can be represented graphically
      by transformation grid which displays type, amount and localization of the shape
      differences. Basis rules of sample composition and landmark positioning to be
      used in GM are considered. At present, rigid (with minimal degrees of freedom) 2D
      morphological objects are most suitable for GM applications. It is important to
      recognize three type of real landmarks, and additionally semi-landmarks and
      "virtual" landmarks. Some procedures of thin-plate spline analysis are considered
      exemplified by some study cases, as well as applications of some standard
      multivariate methods to GM results. They make it possible to evaluate correlation
      between different shapes, as well as between a shape and some non-shape variables
      (linear measurements etc); to evaluate the differences among organisms by shape
      of a morphological structure; to identify landmarks which most accounted for both
      correlation and differences between the shapes. An annotated list of most popular
      softwares for GM is provided.

PMID- 12510588
TI  - [Modeling of swarm formation as a consequence of autotaxis].
AB  - The simple model of school and swarm formation is proposed within the frameworks
      of Eulerian space models (reaction-diffusion-advection system). Assuming that the
      schooling and the processes of birth-and-death act on different time scales, we
      have excluded the local kinetics of species (the reaction term) from the model.
      The spatial dynamics of animals is circumscribed by scalar field of density and
      vector field of velocity. The basis of animal aggregation in space is the ability
      of animals to move in certain direction, i.e. taxis. As an example of swarming
      strategy the behavior of midges is taken: we presume that individuals accelerate
      towards higher swarm density but change direction when the density exceeded some
      maximum. In other words, acceleration of movement is assumed to be proportional
      (with density-dependent coefficient of proportionality) to the gradient of
      species density. This statement poses the equation for species velocity. Thus,
      our model adds the differential equation for velocity of autotaxis to the
      standard advection-diffusion model. The linear analysis of 1D problem with zero
      flux boundary conditions has showed that homogeneous nonzero equilibrium looses
      its stability when the movement rate of animals (coefficient of proportionality
      in velocity equation) overpasses some bifurcation value. The numerical
      experiments have confirmed analytical results, displaying stationary spatially
      heterogeneous solution (standing waves) for the detected supercritical value of
      the movement rate.

PMID- 12510589
TI  - [The vegetation adventivisation through perspective of modern ecological ideas].
AB  - Results of study of vegetation adventivisation (increase in proportion of
      invasive species) correspond to the theory of present ecology that denies general
      universal laws. Diverse features of invasive species play different role under
      various ecological conditions and at various time and space scale. The
      invasibility of communities under various conditions is determined by combination
      of different biotic and abiotic factors though it is obvious that most of
      invasive species are characterized with the high seed production, well developed
      vegetative propagation, windblown pollination, high plasticity and effective use
      of resources, low consumption by herbivores. The definition of an "ideal invasive
      species" or an "ideal invasible community" is impossible. The regularities of
      vegetation adventivisation can be observed clearly only at very large scale.

PMID- 12510590
TI  - [The structure and dynamics of woodreed Calamagrostis canescens population: a
      modelling approach].
AB  - A scale of ontogenetic states has been developed for woodreed Calamagrostis
      canescens, a perennial species dominating the grass layer of fell forest areas.
      The population structure is considered as a set of age-stage groups of
      individuals differing both in the ontogenetic stage and the chronological age
      measured in years. to describe the dynamics through years a special kind of
      matrix formalism has been proposed which is reducible neither to the classic
      Leslie matrix for an age-structured population, nor to the well-known Lefkovitch
      matrix for a stage-structured one, and which does not suffer from excessiveness
      of the "two-dimensional" representation for the structure implying the projection
      matrix of a block pattern. It has been shown however that the protection matrix
      corresponding to C. canescens life-history graph embodies the canonical features
      of matrix formalism for structured population dynamics, such as the exponential
      population growth or decline, the convergence to a stable equilibrium structure,
      the calculable indicator of growth/decline/equilibrium (i.e., a measure of the
      population reproductive potential) as well as possibility to determine the
      relative reproductive value of each group. On the other hand, "left-sidedness of
      the age spectrum", a property that is often observed in real populations and is
      inherent in Leslie models of growing populations, may fail in the age-stage
      structured model. The aggregation of age-stage groups into the age classes is
      possible only under special strict relationship among the age-stage-specific
      vital rates of the population. The both circumstances serve a methodical
      indication that an additional dimension such as the stages, for example, ought to
      be introduced into the age structure of the model population.

PMID- 12510591
TI  - Presentations by youth to Auckland emergency departments following a suicide
      attempt.
AB  - The objective of this study was to describe the population of European youth (15
      24 years) presenting to emergency departments (EDs) at one of the three Auckland
      public hospitals following attempted suicide; and to identify factors associated
      with presentations to EDs by these youth. A 1-year medical record review was
      undertaken. A total of 212 presentations (196 individuals) occurred during the
      surveillance; alcohol was present for 29%. Attempts involving alcohol were more
      likely to occur at weekends (P < 0.01); involve cutting and piercing (P < 0.05);
      be undertaken by employed people (P < 0.05), and be undertaken by those not
      residing with family (P < 0.01). Two groups of particular concern were
      identified: those who involved alcohol in their attempt; and those who
      represented during the study period following multiple suicide attempts. These
      findings have implications for immediate care within an ED setting, and long-term
      follow-up healthcare options for distressed young people.

PMID- 12510592
TI  - Psychiatric and social outcomes of a rural district general hospital in the
      1990s.
AB  - This study investigates the psychiatric and social outcomes of treatment by the
      psychiatric unit of a district general hospital in a semirural region of
      Australia. The study is a naturalistic investigation of a routine clinical
      service, and utilizes a longitudinal panel design. Repeat interviews at
      admission, 1 month and 1 year later were conducted with all consenting
      respondents (n = 57) with a diagnosis of schizophrenia, bipolar disorder or
      related condition, as well as with their nominated relatives. Patients showed
      significant improvements on clinical measures (P < 0.001) and a high rate of
      continuation of medication. Most measures of social functioning showed
      improvement although few were statistically significant. Patients and relative
      satisfaction was high. Relative worry showed significant improvement in the first
      month (P < 0.05). There was a high rate of readmission (31 patients) and mean
      days in hospital were also high at 43 days. These results suggest that basic
      district general hospital care, operating under both budgetary restrictions and
      the difficulties associated with recruiting staff can nonetheless provide a
      credible service. However, the results fall short of what research tells us can
      be achieved when services are adequately funded and more specifically targeted to
      meet patient needs.

PMID- 12510593
TI  - Advanced 'prescribing' of nurses' emergency holding powers under New Zealand
      mental health legislation.
AB  - Since the mid-19th century doctors have exercised almost exclusive control in
      health professionals' decisions concerning compulsory assessment and treatment of
      the mentally ill. This control has the potential to compromise the legitimate
      professional practice of other mental health professionals. A new approach to
      mental health legislation has seen the involvement of a range of health
      professionals in legislated mental health roles, including the power of
      registered nurses to detain patients in hospital under Section 111 of the New
      Zealand Mental Health (Compulsory Assessment and Treatment) Act (1992). Under
      this Section a nurse who believes that a voluntary patient meets the legal
      criteria of the Act can independently detain the patient for a period of up to 6
      hours, pending further assessment by a medical practitioner. However, anecdotal
      evidence and a clinical audit undertaken by the authors suggest some doctors
      'prescribe' Section 111 at the time of admission. This practice instructs nurses
      to initiate Section 111 if particular voluntary patients choose to leave
      hospital. This study outlines practice issues resulting from 'prescribing'
      Section 111; provides a legal critique of medical practitioners' involvement in
      this practice; and makes recommendations for guidelines toward a more
      constructive use of Section 111.

PMID- 12510594
TI  - Is depression normal in human beings? A critique of the evolutionary perspective.
AB  - To the evolutionary biologist human beings at every stage of their development
      represent 'compromises' in their continual adaptation to their changing
      environments. Using a neo-Darwinian perspective, evolutionary psychiatrists such
      as Randolph Nesse (Professor of Psychiatry at the University of Michigan) argue
      that while natural selection does not shape disease itself, it does shape human
      traits and therefore vulnerability to disease. Accordingly, for him, depression
      is a human emotion which may represent a surviving positive response and is
      therefore not always pathological. This critique examines Nesse's principal
      arguments and reveals a number of weaknesses in those arguments. The article
      concludes with a review of the therapeutic and preventive implications of his
      evolutionary perspective on depressive states as well as some implications for
      mental health nurses.

PMID- 12510595
TI  - Transformative change of self: the unique focus of (adolescent) mental health
      nursing?
AB  - In mental health nursing, inadequate nursing practice research has resulted in a
      deficit of knowledge concerning the nurse-client relationship; an area seen as
      the heart of practice. In turn, the specialty has experienced difficulty in
      identifying its unique domain of practice. Findings from a hermeneutic study into
      adolescent mental health nursing explicated its practice knowledge. These
      findings include: (i) 'engaging in therapeutic relationships'; (ii) 'guiding the
      potential for change'; and (iii) 'facilitating positive outcomes'. A higher order
      finding was named 'fostering a functional self'. These findings are discussed.
      Findings point to the nature, purpose and processes of the nurse-client
      relationship, and to outcomes from that relationship. It is suggested they also
      represent a beginning understanding of the specialty's unique contribution to
      nursing; that mental health nursing fosters transformative change of self.

PMID- 12510596
TI  - Experience, knowledge and attitudes of mental health staff regarding clients with
      a borderline personality disorder.
AB  - A survey of mental health staff experience, knowledge and attitudes regarding the
      management of clients with a diagnosis of borderline personality disorder (BPD)
      aimed to obtain baseline data to provide direction for developing planned
      education and determining staff willingness to participate in such training. A 23
      item questionnaire was developed and posted to mental health staff in a public
      Area Mental Health Service in New South Wales (n = 516). A total of 229 staff
      completed the questionnaire. Most staff (85%) reported having contact with
      clients who have a diagnosis of BPD at least once a month or more frequently,
      with 32% of respondents reporting daily contact. Eighty per cent of respondents
      found dealing with clients who have a BPD to be moderate to very difficult; 84%
      of staff felt that dealing with this client group was more difficult than dealing
      with other client groups. Most staff (82%) believed that, as mental health
      professionals, they had a role in the assessment, management and referral of
      clients with BPD, as well as in educating and providing information. Staff
      readily identified resources which would be helpful to them when working with
      such clients. It was encouraging to see that the majority of staff (95%)
      indicated their willingness to gain further education and training in the
      management of these clients. Although many staff believed they were knowledgeable
      about and confident in managing these clients, most staff also indicated
      difficulties posed by these clients and perceived a need for further education
      and training in this area.

PMID- 12510597
TI  - The validity and reliability of the measurement of the concept 'expressed
      emotion' in the family members and nurses of Hong Kong patients with
      schizophrenia.
AB  - This study aimed to test the validity and reliability of three measures of
      expressed emotion in a sample of family members and nurses of Hong Kong Chinese
      people with schizophrenia. Little research has been done in Hong Kong in relation
      to family expressed emotion (EE) and schizophrenia so the present study set out
      to pilot some measures that could become reliable and valid measures for future
      clinical studies. The Adjective Check List (ACL) and the Family Attitude Scale
      (FAS) were compared to EE ratings obtained after a brief interview. The ratings
      were made based on the conceptual framework of the Camberwell Family Interview,
      which includes the dimensions of criticism, hostility and emotional over
      involvement. Twenty-one family members and their primary nurses participated in
      the study which revealed that 13 of the family members and 10 of the primary
      nurses were rated as high EE, either in terms of criticism, emotional over
      involvement or both, based on the interview. The differences in the mean FAS
      scores between the high EE groups and the low EE group was large but not
      statistically significant, and there was a significant correlation between the
      FAS and the brief interview. The ACL revealed some interesting results in terms
      of the way relatives and nurses see themselves responding to the person with
      schizophrenia and vice versa. Recommendations for future studies and family
      education strategies are made.

PMID- 12510600
TI  - Dental profession is under attack.

PMID- 12510598
TI  - Ethical practice guidelines: an evaluation.
AB  - Ethical practice guidelines (EPGs) were developed for use in Central Sydney Area
      Mental Health Service to guide contemporary mental health nursing practice and
      serve as a resource for clinical mental health nurses in relation to their
      professional conduct and practice. This survey of mental health nurses aimed to
      ascertain feedback on the application of the EPGs in the clinical arena. Nurses
      from the Central Sydney Area Mental Health Service (n = 350) were asked to
      complete a 15-item survey developed by the authors. A total of 121 nurses
      completed the survey. Findings from the survey reveal that the information
      provided in the EPGs is useful (91%) and the EPGs provide sufficient guidance for
      practice (94%). Most respondents (96%) reported feeling confident dealing with
      ethical practice situations and 75% indicated interest in further education and
      training in this domain. Findings from this survey support the need to explore
      avenues to facilitate education, discussion and reflective practice in relation
      to ethical mental health nursing practice.

PMID- 12510601
TI  - Member defends dental schools, students, board exam.

PMID- 12510602
TI  - Testing your diagnostic skills(#65). Case No.1. Drug-induced pigmentation.

PMID- 12510603
TI  - Select proper germicides for clinical tasks.

PMID- 12510604
TI  - Ergo-centric ultrasound.

PMID- 12510605
TI  - The new age of healthcare.

PMID- 12510606
TI  - A fantastic journey: 3D cardiac ultrasound goes live.
AB  - With a recent product introduction, live 3D echo is now clinically practical. It
      is already beginning to have a profound impact on the way we care for patients at
      The University of Chicago Medical Center. In the past, dynamic cardiac 3D
      rendered images were possible by sequentially acquiring 2D images and then using
      a workstation to input 2D images for Cartesian coordinate conversion and volume
      rendering. Outside research settings, this time-consuming process proved
      cumbersome and was simply impractical. Now that these technical and practical
      issues have been addressed, real-time 3D cardiac sonography has great potential
      to impact both patient care and throughput in a number of ways, including better
      pre- and post-surgical planning, improved measurement of heart function,
      decreased exam times, and enhanced communication between clinicians and their
      patients. With real-time 3D cardiac ultrasound images, clinicians will be able to
      better quantify size, shape and function of the heart. However, the most
      important contribution of real-time 3D sonography in cardiology may be
      improvement in locating abnormalities for surgical planning. The new technology
      will also provide important information regarding surgical outcomes. A great
      benefit to obtaining more diagnostic information and higher diagnostic confidence
      from real-time 3D cardiac ultrasound images is that it could lead to more rapid
      exam times and the reduction of patient wait times. Being able to see the whole
      heart makes examinations more simple and rapid, benefitting the staff and
      patient. The utility of this technology is unusually broad, as it is able to move
      beyond diagnostics into a key role in therapeutic procedures. As with any new
      technology, there will be a learning curve to understanding 3D imaging. Though
      the matrix transducer is somewhat larger than a standard 2D probe, the ergonomics
      are quite similar. The interface of the ultrasound unit is also very user
      friendly. Because real-time 3D cardiac ultrasound involves looking at the heart
      as if you are holding it in your hands, with the additional ability to turn it
      any way you want, we expect that the transition from 2D to 3D will be easily
      achieved.

PMID- 12510607
TI  - PACS support: the radiology approach.
AB  - In 1999, Rex Healthcare, a 394-bed facility located in Raleigh, N.C., faced a
      growing problem. The radiology department was performing a total of 130,000
      procedures a year, running out of space to store the film, and having trouble
      managing the file room. While the IT department was focused on the Y2K scare,
      radiology forged ahead with a plan to implement PACS on its own at Rex Hospital.
      Rex had installed a mini-PACS system for ultrasound in 1996, but there was no
      internal support for the system's hardware or software. Being the first in the
      area to implement PACS, Rex wasn't able to recruit anyone locally to support the
      system, so they decided to take two areas that PACS had a great impact on and use
      their own people. The director of radiology asked the RIS analyst and the Film
      Library manager, both of whom were registered technologists, to implement and
      support the PAC system. The key to PACS support is not computer knowledge,
      although it helps. The key is to understand the radiology department as a whole
      and the workflow from within, which makes it hard to fully support from an IT
      perspective. The current PACS team at Rex is composed of a PACS analyst, system
      support specialist and an electronic imaging center manager. When we went live
      with PACS, it was obvious that not all of the existing file room personnel would
      make the technology leap, which they realized themselves. We didn't push anybody
      out, but we did raise the bar of expectations. By redefining job descriptions and
      having the EITs (electronic imaging technologists) become more involved,
      increased respect was quite evident among the hospital staff. The clerks that
      once only hung and filed films are now troubleshooting CD burners, teaching
      physicians the PACS, and filming necessary exams. The final key to success is to
      take ownership of your system. By taking ownership, I mean that a PACS team
      should be established to do troubleshooting and first-line support, know the
      servers and application, and feel comfortable performing daily checks and tasks.
      Being an advanced radiology PACS site in our area, we have become an important
      facility for site visits. We take site visits very seriously, and have composed a
      package that includes information about the hospital, network/modality diagrams,
      EIT job descriptions, PACS information and various time studies that we have
      completed since going firmless. An administrator with a vision and strong support
      from within will get a PACS up and running, but ongoing upkeep requires a team
      that is dedicated to the success of the project. By taking ownership of the
      system and following the keys to success, a department has the ability to
      reengineer radiology workflow not just in the hospital, but in the community as
      well.

PMID- 12510608
TI  - Micromanagement--a costly management style.
AB  - Micromanagement can be advantageous in certain short-term situations, such as
      while training new employees, increasing productivity of underperforming
      employees, controlling high-risk issues, and when there can be no question of who
      is in charge. However, the costs associated with long-term micromanagement can be
      exorbitant. Symptoms such as low employee morale, high staff turnover, reduction
      of productivity and patient dissatisfaction can be associated with
      micromanagement. The negative impacts are so intense that it is labeled among the
      top three reasons employees resign. Ultimately, micromanagement leads to
      decreased growth potential in a department. Managers who put too much emphasis on
      daily operational details can miss the broader picture and fail to plan for
      departmental expansion. Eventually, many micromanagers find themselves at
      considerable risk of burnout. Changing behavior associated with micromanagement
      can be a lengthy and difficult process. As with most problems, the first step is
      to realize that there is behavior that needs to be changed and to understand how
      it negatively impacts the department. Conducting a self-assessment of one's
      leadership style can be advantageous in this process. The true task is to find a
      balance between effectively performing daily obligations and strategically
      planning for the future. This task typically involves proper delegation of
      duties, and that in itself is a difficult challenge. Proper delegation of tasks
      may be the primary key to combating micromanaging behavior, however, some other
      suggestions include: 1. Develop a vision of what the department will look like in
      the future. 2. Hire people with the right skills for the job. 3. Develop a policy
      and procedures manual. 4. Develop solid lines of communication between managers
      and subordinates. 5. Expect some employee errors. Mistakes are an important
      process in the learning experience and should be viewed as a training expense.
      Employees who are allowed to be self-directed will be motivated to be more
      productive. Staffing issues such as low morale and high turnover will decrease;
      patient satisfaction will increase simultaneously.

PMID- 12510609
TI  - The staffing shortage: AHRA responds.
AB  - The AHRA Board of Directors formed a Long-Term Staffing Task Force to study the
      question, "Should AHRA become involved in the resolution(s) of the current
      staffing crisis, and if so how?" Because the background information that could be
      gathered was extensive, the Task Force used the following four questions to guide
      its activity: SENSITIVITY TO MEMBERS' VIEWS: What do we know about the needs,
      wants and preferences of our members, prospective members and customers relevant
      to a decision to become involved in activities to resolve the staffing crisis?
      FORESIGHT ABOUT FUTURE ENVIRONMENT: What do we know about the current and
      evolving dynamics of our profession relevant to a decision to become involved in
      activities to resolve the staffing crisis? INSIGHT INTO THE ORGANIZATION: What do
      we know about the strategic position and internal capacity of our organization
      relevant to a decision to become involved in activities to resolve the staffing
      crisis? CONSIDERATION OF OUR CHOICES: What are the ethical implications of our
      choices relevant to a decision to become involved in activities to resolve the
      staffing crisis? After considerable investigation and discussion, the Task Force
      made the following recommendations to the Board: RAISE AWARENESS OF OUR
      PROFESSION: Expand the number of radiologic technologists in the workforce by
      increasing the diversity of our students and by changing the traditional method
      in which we educate students (i.e., full-time, day clinical education). Create a
      quality monitor useful to the majority of radiology leaders to begin to
      systematically document the shortage. Support limited licensure and/or create a
      defined position of "staff extender" for radiologic technology.

PMID- 12510610
TI  - 2003 coding update.

PMID- 12510611
TI  - Multislice CT service--cost versus revenue.

PMID- 12510612
TI  - 2002 medical imaging time capsule.

PMID- 12510613
TI  - New codes you need to know.

PMID- 12510614
TI  - Keep tabs on who sees what.

PMID- 12510615
TI  - What's the Washington outlook now?

PMID- 12510616
TI  - Expense survey: what it costs to practice today.

PMID- 12510617
TI  - How I got through to Kari's mother.

PMID- 12510618
TI  - Malpractice premiums; soaring again.

PMID- 12510619
TI  - Why I had to pay my patients' lab bills.

PMID- 12510620
TI  - Does tort reform protect groups, too?

PMID- 12510621
TI  - 8 ways to get more done.

PMID- 12510622
TI  - Experience is the best doctor, too.

PMID- 12510623
TI  - Jerry Brown, MD. Bodyguards, land mines, and medicine.

PMID- 12510624
TI  - 150 best financial advisers for doctors.

PMID- 12510625
TI  - When another doctor messes up.

PMID- 12510626
TI  - Boardroom disclosure. In light of recent corporate scandals, AHA board execs
      debate whether they should serve on the boards of for-profit companies.
AB  - Corporate integrity is the topic du jour, and now it has emerged among the
      leadership of the American Hospital Association, where a divide exists over
      whether AHA board executives should serve concurrently on the boards of for
      profit firms selling goods to hospitals. Fred Brown (left), AHA chairman in 1999,
      is one of several former AHA chair officers who served on the boards of privately
      held firms during their tenures.

PMID- 12510627
TI  - Spending spree catches up with Doctors Community.

PMID- 12510628
TI  - Room for improvement. Report: access to hospice, palliative care 'mediocre'.

PMID- 12510629
TI  - A blurry picture. Mammography, though marred by controversy, is still the most
      valued tool for detecting breast cancer. But a continuing shortage of
      radiologists takes some luster off the gold standard.

PMID- 12510630
TI  - The European Federation of Psychiatric Trainees (EFPT)--an integral part of the
      European harmonisation of psychiatric education and practise.
AB  - The European Federation of Psychiatric Trainees (EFPT) is the umbrella
      organisation for national European psychiatric trainees' organisations. It
      primarily aims at advancing and harmonising the quality of psychiatric education
      and practise. As a permanent observer member of the European Board of Psychiatry
      and the European Board of Child and Adolescent Psychiatry, the EEPT actively
      participates both in the development of educational guidelines and in the
      evaluation of psychiatric training institutions in Europe. Through its annually
      held European Forum for all Psychiatric Trainees the EEPT provides a unique
      opportunity for the exchange of training-related experiences and opinions on
      current developments in psychiatry. This is the first comprehensive overview of
      the history, goals, and political work of the EEPT, depicting its evolution from
      an informal meeting of psychiatric trainees to a recognised organisation
      representing over 10,000 young psychiatrists throughout Europe.

PMID- 12510631
TI  - Treatment interruption consequences unknown.

PMID- 12510632
TI  - To treat or not to treat...when that is the question.

PMID- 12510633
TI  - Fatigue may be sign of anemia.

PMID- 12510634
TI  - Adherence matters. Therapeutic drug monitoring (TDM) may detect drug failure.

PMID- 12510635
TI  - New diarrhea treatment available for sale as dietary supplement.

PMID- 12510636
TI  - Eye on the finish line. The art of running a healthy marathon.

PMID- 12510637
TI  - Your benefits & you. GR: how to spell relief.

PMID- 12510639
TI  - Funerals, prayers and hope mark Worlds AIDS Day as disease spreads.

PMID- 12510638
TI  - Immigration. Assistance gets tougher.

PMID- 12510640
TI  - Report says South leads U.S. in new HIV infections, AIDS.

PMID- 12510641
TI  - Testing. HIV misdiagnosis 'unfortunate', but not intentional.

PMID- 12510642
TI  - Canadian High Court upholds Glaxo Wellcome AZT patent.

PMID- 12510643
TI  - Private sector crucial for improving global health.

PMID- 12510644
TI  - Tracking shows effort fails to halt spread of AIDS.

PMID- 12510645
TI  - UNAIDS indicates progress on global HIV/AIDS status in 2002.

PMID- 12510646
TI  - New York told to stop arresting needle exchange recipients.

PMID- 12510647
TI  - Needle exchange. Roe ruling results in dismissal of other possession cases.

PMID- 12510648
TI  - Massachusetts court upholds statewide needle possession.

PMID- 12510649
TI  - Disclosure. Patient allowed to sue doctor for revealing HIV status.

PMID- 12510650
TI  - HIV vaccine development company faces bankruptcy.

PMID- 12510651
TI  - Web site launched to educate public about immunization.

PMID- 12510652
TI  - Busted! Fugitive felons and the long arm of the Social Security Administration.

PMID- 12510654
TI  - Positive Living 1992:2002. Retrospective.

PMID- 12510653
TI  - Will power.

PMID- 12510655
TI  - Triple PI therapy--perhaps more is not better.

PMID- 12510656
TI  - Resistance: a shifting paradigm.

PMID- 12510657
TI  - Longitudinal studies of the role of NRTIs in fat loss.

PMID- 12510658
TI  - All-cause mortality rates in HIV-infected patients with coronary artery disease.

PMID- 12510659
TI  - Antiretroviral rounds. "Doc, I've been making mistakes".

PMID- 12510660
TI  - A dearth of groundbreaking data at 14th international conclave of HIV medical
      community.

PMID- 12510661
TI  - One step ahead of us. XIV International AIDS Conference, July 7-12, 2002 -
      Barcelona.

PMID- 12510662
TI  - GALEN in action.

PMID- 12510663
TI  - Parental exposure to organic solvents and reduced birth weight.
AB  - The authors investigated the association of birth weight with maternal and
      paternal exposure to organic solvents in 1,222 couples employed in a large
      petrochemical corporation in Beijing, China, during the period between 1994 and
      1998. A trained interviewer assessed parental exposures to organic solvents. The
      authors used generalized additive models to examine the association between birth
      weight and parental exposure to organic solvents. After the authors adjusted for
      potential confounders, maternal exposure to solvents was significantly associated
      with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and
      reduced birth weights of female babies and of younger mothers' babies were
      statistically significant. Maternal exposure to organic solvents was associated
      with reduced birth weight in this population, but paternal exposure to organic
      solvents was not similarly associated.

PMID- 12510664
TI  - Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic
      criteria.
AB  - Epidemiologic studies have helped to define the prevalence and incidence of PM,
      DM, and IBM and have highlighted differences in risk between men and women and in
      the age at onset for the different forms of myositis. Additionally, these studies
      have shown that there is a substantially higher risk of PM and DM in certain
      racial groups which is likely to be genetically determined. These differences are
      all likely to be fundamental in terms of the pathogenesis of these diseases but,
      as yet, their full significance remains uncertain. They do, however, suggest that
      the interplay between genetic and environmental initiating factors is different
      in the three disorders. Additional population-based studies in homogeneous racial
      groups, in parallel with studies of susceptibility genes for autoimmune disease,
      such as those encoding the MHC and inflammatory cytokines, are needed to throw
      further light on the role of genetic factors in the pathogenesis of the IIMs
      [47]. Because of the paucity of epidemiologic data on IBM, further studies are
      required to determine the degree of variation in prevalence in different
      populations and racial groups, as well as the consistency of the male association
      and age spectrum of manifestations of the disease. The particularly strong
      association with DR3 in this form of IIM [48] clearly points to the importance of
      genetic factors in pathogenesis, but further studies of DR3-associated genes in
      the MHC and of other candidate genes are needed to define more precisely the
      genes that convey susceptibility to the disease in different racial groups.
      Epidemiologic studies also have the potential to identify environmental factors
      that may play a part in disease initiation in genetically susceptible
      individuals. Seasonal patterns of disease onset have been reported, particularly
      in patients with DM [49-51] as well as seasonal variation in the frequency of
      relapses [52], pointing to the probable involvement of intercurrent infections,
      ultraviolet light exposure, or other environmental factors in disease initiation
      and reactivation. Further prospective studies are required to determine the
      contribution of environmental exposures and how they interact with genetic
      susceptibility factors to lead to myositis. One of the major limitations of a
      number of the previous epidemiologic studies is the lack of precision in the
      diagnostic criteria used and the classification of cases of IIM. The Bohan and
      Peter criteria [1] which were used in most studies after 1975, were introduced
      before IBM was recognized as an entity distinct from PM; most of the published
      incidence and prevalence figures for PM are therefore likely to be inaccurate.
      Multicentered, interdisciplinary, prospective studies, incorporating
      comprehensive clinical, laboratory, and pathologic information, are needed to
      develop and validate better diagnostic and classification criteria and to
      determine the true prevalence and incidence of the many forms of IIM.

PMID- 12510665
TI  - Medicare program; revisions to payment policies under the physician fee schedule
      for calendar year 2003 and inclusion of registered nurses in the personnel
      provision of the critical access hospital emergency services requirement for
      frontier areas and remote locations. Final rule with comment period.
AB  - This final rule with comment period refines the resource-based practice expense
      relative value units (RVUs) and makes other changes to Medicare Part B payment
      policy. In addition, as required by statute, we are announcing the physician fee
      schedule update for CY 2003. The update to the physician fee schedule occurs as a
      result of a calculation methodology specified by law. That law required the
      Department to set annual updates based in part on estimates of several factors.
      Although subsequent after-the-fact data indicate that actual increases were
      different to some degree from earlier estimates, the law does not permit those
      estimates to be revised. A subsequent law required estimates to be revised for FY
      2000 and beyond. Although we have exhaustively examined opportunities for a
      different interpretation of law that would allow us to correct the flaw in the
      formula administratively, current law does not permit such an interpretation.
      Accordingly, without Congressional action to address the current legal framework,
      the Department is compelled to announce herein a physician fee schedule update
      for CY 2003 of -4.4 percent. Because the Department would adopt a change in the
      formula that determines the physician update if the law permitted it, we have
      examined how proper adjustments to past data could result in a positive update.
      The Department believes that revisions of estimates used to establish the
      sustainable growth rates (SGR) for fiscal years (FY) 1998 and 1999 and Medicare
      volume performance standards (MVPS) for 1990-1996 would, under present
      calculations, result in a positive update. The Department intends to work closely
      with Congress to develop legislation that could permit a positive update, and
      hopes that such legislation can be passed before the negative update takes
      effect. Because the Department wishes to change the update promptly in the event
      that Congress provides the Department legal authority to do so, we are requesting
      comments regarding how physician fee schedule rates could and should be
      recalculated prospectively in the event that Congress provides the Department
      with legal authority to revise estimates used to establish the sustainable growth
      rates (SGR) and for 1998 and 1999 and the NVPS for 1990-1996. The other policy
      changes concern: the pricing of the technical component for positron emission
      tomography (PET) scans, Medicare qualifications for clinical nurse specialists, a
      process to add or delete services to the definition of telehealth, the definition
      for ZZZ global periods, global period for surface radiation, and an endoscopic
      base for urology codes. In addition, this rule updates the codes subject to
      physician self-referral prohibitions. We are expanding the definition of a
      screening fecal-occult blood test and are modifying our regulations to expand
      coverage for additional colorectal cancer screening tests through our national
      coverage determination process. We also make revisions to the sustainable growth
      rate, the anesthesia conversion factor, and the work values for some
      gastroenterologic services. We are making these changes to ensure that our
      payment systems are updated to reflect changes in medical practice and the
      relative value of services. This final rule also clarifies the enrollment of
      physical and occupational therapists as therapists in private practice and
      clarifies the policy regarding services and supplies incident to a physician's
      professional services. In addition, this final rule discusses physical and
      occupational therapy payment caps and makes technical changes to the definition
      of outpatient rehabilitation services. In addition, we are finalizing the
      calendar year (CY) 2002 interim RVUs and are issuing interim RVUs for new and
      revised procedure codes for calendar year (CY) 2003. As required by the statute,
      we are announcing that the physician fee schedule update for CY 2003 is -4.4
      percent, the initial estimate of the sustainable growth rate for CY 2003 is 7.6
      percent, and the conversion factor for CY 2003 is $34.5920. This final rule will
      also allow registered nurses (RNs) to provide emergency care in certain critical
      access hospitals (CAHs) in frontier areas (an area with fewer than six residents
      per square mile) or remote locations (locations designated in a State's rural
      health plan that we have approved.) This policy applies if the State, following
      consultation with the State Boards of Medicine and Nursing, and in accordance
      with State law, requests that RNs be included, along with a doctor of medicine or
      osteopathy, a physician's assistant, or a nurse practitioner with training or
      experience in emergency care, as personnel authorized to provide emergency
      services in CAHs in frontier areas or remote locations.

PMID- 12510666
TI  - Acrylamide and N-methylolacrylamide poisoning in a herd of Charolais crossbreed
      cattle.
AB  - Seven beef cattle from a herd accidentally exposed to acrylamide and N
      methylolacrylamide while grazing were observed for eight months. They showed
      clinical signs of impaired nerve function, mainly in the hindlegs, with varying
      degrees of weakness and ataxia. The animals were irritable, nervous and
      hypersensitive to touch. Both pupils of the most badly affected animal were
      dilated and it had poor pupillary light responses; it also showed signs of axonal
      neuropathy. Selected haematological and clinical chemistry variables were normal.
      The severity of the neurological signs was correlated with the concentrations of
      haemoglobin adducts of acrylamides. The animals recovered substantially after
      their exposure. The gestations of four of the animals which were in calf
      proceeded normally.

PMID- 12510667
TI  - Ontogeny of hematopoiesis: examining the emergence of hematopoietic cells in the
      vertebrate embryo.
AB  - Hematopoietic stem cells (HSCs) are responsible for generating all the lineages
      of the blood. During vertebrate development, waves of hematopoietic activity can
      be found in distinct anatomical sites, and they contribute to both embryonic and
      adult hematopoiesis. The origin of the HSCs that ultimately give rise to all the
      adult blood lineages has been a controversial issue in the field of
      hematopoiesis. Studies of amniotes have linked HSC activity to the aorta-gonad
      mesonephros (AGM) region, whereas others suggest that the yolk sac is the true
      source of HSCs. This review describes both primitive and definitive hematopoiesis
      in mice, humans, chicks, frogs, and zebrafish and examines the current debate
      over the embryonic origins of HSCs.

PMID- 12510668
TI  - [Unstable angina and acute myocardial infarction: main recent trials].

PMID- 12510671
TI  - Proceedings of the Contrast Media Research Symposium. Woodstock, Vermont, USA.
      September 12-17, 1999.

PMID- 12510669
TI  - [Congestive heart failure and acute myocardial infarction: latest  trials with
      beta-blocking agents].

PMID- 12510672
TI  - Abstracts of papers presented at the International Symposium on Current
      Developments in Drug Discovery for Tuberculosis. January 14-17, 2002.

PMID- 12510673
TI  - [63rd National Congress of the SIMLII. Sorrento, Italy, 10 November 2000.
      Proceedings and abstracts].

PMID- 12510674
TI  - Abstracts of the essay programs of the 56th annual meeting of the American
      Academy of Oral and Maxillofacial Pathology.

PMID- 12510675
TI  - Faculty matters. Thomas J. Doyle.

PMID- 12510676
TI  - Abstracts from the 3rd International Conference on Nearfield Optical Analysis.
      Sao Paulo, Brazil. June 25-26, 2002.

PMID- 12510677
TI  - Kitchen technologies and mealtime rituals: interpreting the food axis at American
      summer camps, 1890-1950.

PMID- 12510678
TI  - Medicine in a world gone mad: Stanislaw Lem's novel Hospital of the
      transfiguration.

PMID- 12510679
TI  - Proceedings of the 7th International Colic Research Symposium. Mancester, July
      2002.

PMID- 12510680
TI  - The triumph of self: the butterfly takes flight.

PMID- 12510681
TI  - Racial bias in health care, still economy-based. [Review of: Byrd, WB and
      Clayton, LA. An American health dilemma: a medical history of African-Americans
      and the problem of race, beginnings to 1900. New York: Routledge, 2000].

PMID- 12510682
TI  - [Varicella prevention in Italy: vaccination strategies. Proceedings of a
      conference. Rome, Italy, February 22, 2002].

PMID- 12510683
TI  - American Statistical Association Conference on Radiation and Health. Deerfield
      Beach, Florida, USA. June 23-26, 2002. Abstracts.

PMID- 12510684
TI  - The thin line between nurse and patient. [Review of: Davis, C. I knew a woman:
      the experience of the female body. New York: Random House, 2001].

PMID- 12510685
TI  - Quest for patients' trust only just begun.

PMID- 12510686
TI  - [The right meaning of the right word].

PMID- 12510687
TI  - Weakness with co-morbid psychopathology: feeding and rest, 1880.

PMID- 12510688
TI  - A pile of rocks.

PMID- 12510689
TI  - Cough and bronchial responsiveness in firefighters at the World Trade Center
      site.

PMID- 12510690
TI  - With humor and determination, a 9/11 survivor heals.

PMID- 12510691
TI  - Low dose acetylsalicylic acid in prevention of pregnancy-induced hypertension and
      intrauterine growth retardation in women with bilateral uterine artery notches.

PMID- 12510692
TI  - IgA nephropathy.

PMID- 12510693
TI  - IgA nephropathy.

PMID- 12510694
TI  - Improvement in papilledema and visual loss after endovascular stent   placement
      in dural sinus thrombosis.
AB  - OBJECTIVE: To report two cases of cerebral venous sinus thrombosis with
      papilledema and visual loss that improved after endovascular stent placement.
      MATERIALS AND METHODS: Retrospective case series from a tertiary ophthalmic
      center. RESULTS: Two cases of venous sinus occlusion treated with angioplasty and
      stenting are described. Both cases experienced improvement in optic disc edema
      and visual function following the procedures. CONCLUSION: Endovascular stent
      placement may relieve increased intracranial pressure and papilledema caused by
      cerebral sinus thrombosis and may prevent further visual loss.

PMID- 12510695
TI  - On the road to California.

PMID- 12510696
TI  - There are good reasons for selecting panoramic radiography to replace the
      intraoral full-mouth series.

PMID- 12510697
TI  - Only fully trained oral medicine clinicians should use cytobrush.

PMID- 12510699
TI  - [Studies on "Ishin shoden" Edited by Dosan Manase (1507-1594): the introduction
      of Satsusho Benchi and the process of its establishment].
AB  - Sanki Tashiro and Dosan Manase are known for their role as founders of the Gosei
      ha school in Japan. Observing that Japanese medicine had not been based on a
      clear theory, they introduced into Japan the satsusho benchi practiced in Chinese
      medicine during the Jin and Yuan dynasties. The basis of this system was to
      examine the patient's condition, then determine the treatment accordingly. Dosan
      Manase in particular employed the satsusho benchi, writing out a new prescription
      each time treatment was required, without reference to existing prescriptions. In
      this study, we carried out an investigation into the "Ishin shoden"edited by
      Dosan Manase, which reveals the process by which Dosan established the new
      satusho benchi system of medicine within the framework of traditional Japanese
      medicine. In the early stages of the process, Dosan prepared prescriptions based
      on existing iou-tou prescriptions, modifying these by adding or removing
      medicines. Then, in the middle period, he prepared prescriptions based on toso
      tou prescriptions, designed on the basis of the kun shin sa shi or Junchen Zuoshi
      theory, again modifying these by adding or removing medicines. In the final stage
      of the process, Dosan ceased this practice of adding or removing medicines from a
      basic prescription, adopting instead the satusho benchi system of writing out a
      new prescription for every treatment. In addition, we consider the reasons why
      the satusho benchi system was not employed by Dosan's successors, and discuss the
      effects of this.

PMID- 12510700
TI  - Current Readings in Nuclear Medicine.

PMID- 12510701
TI  - Leveling the health delivery field.

PMID- 12510702
TI  - Incidence and risk factors for cardiovascular disease in African Americans with
      diabetes: the Atherosclerosis Risk in Communities (ARIC) study.
AB  - To determine the incidence rate of cardiovascular disease (CVD) and its
      association with conventional and less well-established risk factors in African
      Americans with diabetes, we studied 741 African Americans aged 45 to 64 years
      with diabetes, in the Atherosclerosis Risk in Communities (ARIC) study. Risk
      factors were measured from 1987 to 1989, and incident CVD (n = 143 coronary heart
      disease (CHD) or stroke events) was ascertained through 1998. The crude incidence
      rate (per 1000 person-years) of CVD was 22.5 (11.9 for CHD and 12.0 for stroke).
      After multivariate adjustments, total cholesterol, prevalent hypertension and
      current smoking were significantly and positively associated with incident CVD
      among these African Americans with diabetes. Among the non-conventional risk
      factors, serum creatinine, factor VIII, von Willebrand factor, and white blood
      cell count were positively and serum albumin negatively and independently
      associated with CVD incidence. Adjusted relative risks for highest versus lowest
      tertiles of these risk factors ranged from 1.77 to 2.13. This study confirms that
      the major risk factors (hypercholesterolemia, hypertension and smoking) are
      important determinants of CVD in African Americans with diabetes. In addition,
      several blood markers of hemostasis or inflammatory response and elevated serum
      creatinine also proved to be CVD risk factors in African Americans with diabetes.

PMID- 12510703
TI  - A review of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and
      accounts for more physician visits and hospital days than any other cardiac
      rhythm disturbance. Atrial filbrillation is incresing in frequency as the
      population ages, and therefore, a knowledge of the clinical spectrum and
      available treatment regimen is essential. Here, we review the pathophysiology,
      clinical presentation, and current status of management. Experience is being
      rapidly accumulated in all of the areas discussed in the management of this
      important clinical entity.

PMID- 12510704
TI  - An assessment of obesity among African-American women in an inner city primary
      care clinic.
AB  - Despite multiple patient assessments and interventions, obesity continues to
      cause significant morbidity and mortality nationwide. This study assesses the
      prevalence of obesity and weight control practices among middle-aged African
      American women. In 1995, 307 women 30 years of age and older were consecutively
      selected in a non-random fashion from three clinic sites located within a public
      university hospital that served largely indigent, inner city African-American
      populations. Interviewers surveyed the respondents using the Centers for Disease
      Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS). The
      prevailing demographic profile of patients in the clinic was middle-aged,
      indigent, ill, and of low educational attainment. Over 35% of individuals were
      classified as being overweight (BMI 25 to 29.9 kg/m2) and 45% were classified as
      being obese (BMI > or = 30 kg/m2). Therefore, more than 80% of individuals in
      this study were either overweight or obese, with BMI exceeding 25 kg/m2. Of the
      overweight and obese African-American women in this study, only 40% were
      attempting current weight loss practices, and weight loss attempts varied
      directly with body mass index. Although 80% of women attempted weight loss by
      restricting caloric intake, only 50% were also using physical activity as part of
      their regime. African-American women in this population have a higher prevalence
      of obesity and encounter great difficulty losing weight. Counselors should
      emphasize the value and ease of adopting a moderate regimen of physical activity
      and not just reducing caloric intake when advising African-American women and
      their peer network.

PMID- 12510705
TI  - Psychosocial burden of sickle cell disease on caregivers in a Nigerian setting.
AB  - In Nigeria, with a high prevalence of sickle cell disease (SCD), families bear
      most of the burden of care for patients with this chronically disabling illness,
      because there are no national social welfare provisions. To assess the severity
      of indices of psychosocial burden among relatives of 24 SCD patients in crisis,
      in comparison with relatives of 57 SCD patients in stable condition. Cross
      sectional study, using a burden instrument and Goldberg's General Health
      Questionnaire. Objective burden indices were significantly higher for SCD in
      crisis. The financial burden of SCD in crisis was significantly higher than the
      burden of disruption of family routines. 57.9% of all caregivers experienced
      little or no difficulty coping with SCD. Relatives with higher educational and
      occupational attainments (compared with those with lower attainments) experienced
      significantly lesser financial burden, disruption of family routines, and
      psychological distress. Compared with a similar study of cancer patients,
      relatives of patients in SCD crisis perceived similar financial, family routine
      burdens and psychological distress scores. Compared with US and UK reports, our
      caregivers were predominantly married and reflected the national range of
      socioeconomic groups. Global rating of burden was significantly predicted by
      disruption of family routines and higher age of caregivers. The psychosocial
      burden of SCD can be significantly reduced by controlling the frequency and
      duration of crises, as well as providing adequate information and socioeconomic
      support to families. Hematology staff should be sensitive to the psychosocial
      dimensions of SCD.

PMID- 12510706
TI  - Chronic obstructive pulmonary disease in OAUTHC Ile-Ife: a ten-year review of
      hospital mortality.
AB  - Chronic obstructive pulmonary disease (COPD) is a spectrum of chronic lung
      disease. The prevalence and incidence of COPD is on the increase globally with an
      attendant increase in morbidity and mortality. There is a lack of data on the
      prevalence and incidence of chronic obstructive pulmonary disease COPD in
      developing countries, which is what prompted this study. We reviewed mortality
      due to COPD in order to identify risk factors for death and possible preventive
      measures. Out of 161 admissions during the review period-1990 to 1999-there were
      41 deaths, accounting for a mortality rate of 25.46%. The highest mortality
      occurred in the sixth and seventh decades of life with a male to female ratio of
      3:1. Chest infections, cor pulmonale, and respiratory failure were the most
      common complications. Extremes of age, lower socio-economic group, smoking (>10
      packs per year), and respiratory tract infection were the most commonly
      identified risk factors for death. Attention should be paid to preventive
      measures to halt the development and progression of the disease. This offers the
      best hope of minimizing mortality.

PMID- 12510707
TI  - Pharmacy assistance programs in a community health center setting.
AB  - Prescription drug costs represent the fastest growing item in health care and are
      a driving force in rapidly increasing health care costs. Community health centers
      serve an indigent population with limited access to pharmaceuticals.
      Pharmaceutical companies sponsor patient assistance programs. These pharmacy
      assistance programs can be developed to facilitate the provision of needed
      pharmaceuticals to this vulnerable population. La Casa de Buena Salud is a rural
      community health center in eastern New Mexico, which has provided access to a
      substantial amount of pharmaceuticals to indigent patients through patient
      assistance programs. Cost savings potential are considerable for a community
      health center and for patients when a pharmacy assistance program is organized
      efficiently and employed systematically. Secondary benefits are derived from the
      entire medical community. While some community health centers currently make
      effective use of pharmaceutical company-sponsored pharmacy assistance programs, a
      comprehensive, long-term approach at a national level may be required.

PMID- 12510708
TI  - Style watch: attitudes toward the attire of African-American medical students,
      residents, and early career physicians.

PMID- 12510709
TI  - Massive life-threatening lower gastrointestinal hemorrhage following hemorrhoidal
      rubber band ligation.
AB  - Hemorrhoids are common, and a significant proportion of patients who have
      hemorrhoids experience symptoms such as bleeding, pain and itching. Endoscopic
      hemorrhoidal ligation is a safe and effective technique indicated for the
      treatment of grade 1 to 3 hemorrhoids, with a high success and low complication
      rate. Complications, when they occur, are minor and may include painful
      thrombosed prolapsed hemorrhoids, slippage of bands, minor rectal bleeding and
      chronic longitudinal ulcer. Rare, potentially life-threatening complications are
      massive hemorrhage and pelvic sepsis. A case of massive, life-threatening lower
      gastrointestinal hemorrhage following endoscopic hemorrhoidal rubber-band
      ligation is presented. Our patient ingested aspirin intermittently following the
      procedure. In a study documenting complications after hemorrhoidal band ligation,
      two of three individuals requiring transfusion for massive hemorrhage were taking
      aspirin on a regular basis. The risk of massive hemorrhage after hemorrhoidal
      rubber band ligation is probably increased by ingestion of nonsteroidal anti
      inflammatory drugs. It may be wise to withhold such drugs soon after the
      procedure, if feasible.

PMID- 12510710
TI  - JNMA article helps doctors treat diabetic patients.

PMID- 12510711
TI  - To the healers (and to their patients who have the right to be healed).

PMID- 12510712
TI  - The protective effects of melatonin, vitamin E and octreotide on retinal edema
      during ischemia-reperfusion in the guinea pig retina.
AB  - PURPOSE: The purpose of this study is to provide evidence that free radical
      damage is a component of retinal ischemia-reperfusion (I/R) injury, and to
      determine whether melatonin, vitamin E and octreotide can protect retina from
      this injury. METHODS: The right eyes of 50 male guinea pigs weighing 500-600 g
      were used. The animals were randomly assigned to group 1 (control), group 2
      (I/R), group 3 (melatonin + I/R), group 4 (vitamin E + I/R) and group 5
      (octreotide + I/R). Groups 3, 4 and 5 received four subcutaneous injections at
      six-hour intervals for total dosage of 10 mg/kg melatonin, 150 mg/kg vitamin E
      and 22 microg/kg octreotide respectively. The first dose of each substance was
      administered 5 minutes before retinal ischemia. Retinal ischemia was induced for
      1.5 hours, then followed by reperfusion for 24 hours. Infections of all three
      substances were repeated at 6, 12 and 18 hours during reperfusion. The animals
      were killed at 24 hours of reperfusion. Sagittal sections of 4 microm were cut
      and stained with hematoxylin and eosin for light microscopic evaluation. The
      average thickness (edema) of the inner plexiform layer for each eye was measured
      in sagittal sections near the optic nerve and expressed in microns. RESULTS: The
      efficacy of each compound had the following relationships: melatonin>vitamin
      E>octreotide in preventing retinal damage by ischemia-reperfusion. The mean
      thickness of the inner plexiform layer was 13.3 +/- 0.8 microm, 25.9 +/- 2. 0
      microm, 20.0 +/- 0. 7 microm, 21.6 +/- 0.7 microm, 23.9 +/- 0.8 microm
      respectively in the control, I/R, I/R plus melatonin, I/R plus vitamin E and I/R
      plus octreotide groups. The thickness of the inner plexiform layer in group 1
      (control) was significantly less than the other groups (p<0.001). The inner
      plexiform layer was thicker in the I/R group than with I/R plus melatonin, I/R
      plus vitamin E and I/R plus octreotide (all p < 0.01). The inner plexiform layer
      was thicker in the I/R plus octreotide group than the I/R plus vitamin E and I.R
      plus melatonin groups both (p < 0.05). Compared to the I/R plus melatonin group,
      the inner plexiform layer was significantly thicker in the I/R plus vitamin E
      group (p < 0. 05). CONCLUSIONS: This study demonstrates a protective effect of
      melatonin, vitamin E and octreotide on the retina during retinal ischemia
      reperfusion injury.

PMID- 12510713
TI  - Expression of Sox9 and type IIA procollagen during ocular development and aging
      in transgenic Del1 mice with a mutation in the type II collagen gene.
AB  - PURPOSE: To study the expression and distribution of transcription factor Sox9
      and type IIA procollagen in the developing and aging eyes of normal and
      transgenic Dell mice carrying pro(alpha)1(II) collagen transgenes with a short
      deletion mutation, which cause ocular abnormalities in this mouse line. METHODS:
      The eyes of Del1 mice were studied on embryonic days E14.5, E16.5 and E18.5, and
      at the ages of 4 and nine months, using their nontransgenic littermates as
      controls. Sox9 and pro(alpha)1(IIA) collagen were detected by RNase protection
      assay and immunohistochemistry. RESULTS: RNase protection assay revealed Sox9
      transcripts in the eyes of Del1 and control mice during development and aging.
      The mRNA for type IIA procollagen had a similar temporal expression pattern. On
      embryonic days E14.5, E16.5 and E18.5, Sox9 was located by immunohistochemistry
      in the nuclei and type IIA procollagen in the extracellular space of the
      developing retina. During growth and aging, the ocular expression of Sox9 mRNA
      and the immunohistochemical reaction for Sox9 antibody diminished, concomitant
      with the reduction in type II procollagen mRNA. However, at the age of nine
      months, levels of Sox9 and type IIA procollagen mRNAs were higher in the
      degenerating eyes of Del1 and control mice. CONCLUSIONS: The similarities in the
      temporo-spatial distribution of Sox9 and type IIA procollagen suggest that this
      transcription factor is involved in the activation of type II collagen expression
      in the eye, as has been demonstrated in prechondrogenic mesenchyme and immature
      cartilage. The increased production of Sox9 and type IIA procollagen in the aging
      retina and vitreous is analogous to degenerating articular cartilage where
      attempted tissue repair has also been observed.

PMID- 12510714
TI  - Response of retinal blood flow to CO2-breathing in humans.
AB  - PURPOSE: To investigate the effect of systemic hypercapnia on retinal
      hemodynamics in humans. METHODS: We studied the effect of breathing a mixture of
      normal air with 5% CO2 for 13 minutes in ten healthy young male volunteers, using
      the Zeiss retinal vessel analyzer for continuous measurement of retinal vessel
      diameter and the blue-field entoptic technique to quantify retinal white blood
      cell flux. In eight other subjects the effect of hypercapnia was measured with
      the Zeiss retinal vessel analyzer and by laser Doppler velocimetry to establish
      retinal blood flow velocity. RESULTS: Retinal arterial and venous vessel
      diameters increased by a maximum of 4.2% and 3.2%, respectively. Peak effect was
      observed after 3 minutes of breathing the mixture of normal air with 5% CO2.
      During hypercapnia red blood cell velocity increased 11.7% and, accordingly,
      retinal blood flow increased 19.1%. White blood cell density and velocity rose
      significantly during hypercapnia, resulting in an increase in white blood cell
      flux (19.2%). CONCLUSIONS: Our data indicate that CO2 induces vasodilation in
      retinal arteries and retinal veins. Retinal blood flow and perimacular white
      blood cell flux increased to the same extent in subjects breathing a mixture of
      normal air with 5% CO2.

PMID- 12510715
TI  - Optical coherence tomography (OCT) angiomatous prolifieration (RAP) in retinal.
AB  - PURPOSE: To verify the utility of optical coherence tomography (OCT) for
      diagnosing retinal angiomatous proliferations (RAP) in patients with exudative
      age-related macular degeneration (AMD). METHODS: Multiple cross-sections were
      taken with OCT from 41 eyes of 39 consecutive patients with AMD and RAP. The
      presence and the location of the angiomatous complexes had already been
      documented by fluorescein angiography (FA) and high-speed confocal indocyanine
      green videoangiography (ICGA). RESULTS: RAP was detectable by OCT scans in all 41
      eyes, appearing as a focal hyper-reflecting area in the neuroretinal layers; it
      was frequently located close to the inner surface of the retinal pigment
      epithelium (29 eyes [70. 7%]). All eyes had either no or only a low-reflecting
      OCTsignal surrounding the RAP, caused by serous intraretinal edema. Only 13 eyes
      (31.7%), however, had large serous retinal detachment (SRD). OCT detected pigment
      epithelium detachment in 31 eyes (75.6%), but none had underlying choroidal
      neovascularization. CONCLUSIONS: OCT findings confirm the intraretinal
      localization of the RAP which are always associated with impressive exudative
      phenomena. OCT is therefore a useful diagnostic tool, adding information to FA
      and high-speed ICGA.

PMID- 12510716
TI  - Optical coherence tomography (OCT) and angiography in patients with angioid
      streaks.
AB  - PURPOSE: To investigate the retinal and choroidal features of angioid streak by
      fluorescein angiography (FA), indocyanine green angiography (ICG-A) and optical
      coherence tomography (OCT). METHODS: We analysed 46 eyes of 23 patients with
      angioid streaks examined at our retina section between March 1998 and June 2000.
      Their mean age was 42.8 years (26-61 years). After a routine ophthalmological
      examination, OCT and simultaneous fluorescein and indocyanine green angiography
      (FA/ICG-A) were done. Color fundus photographs were also taken. RESULTS: A peau
      d'orange appearance and angioid streaks were more numerous and apparent with ICG
      A than FA. In two eyes (4.3%), some streaks that were well visualized on FA were
      not visible on ICG-A. Twenty eyes (43.5%) had macular complications and 26
      (56.5%) were normal. Occult choroidal neovascularization (CNV) was diagnosed by
      ICG-A. Nine eyes had occult, and 11 had classic CNV Ruptures of Bruch's membrane
      were hypofluorescent in 20 (43.5%) and hyperfluorescent in 26 eyes (56.5%). Optic
      disc drusen were detected in both eyes of one patient (4.3%). Localized
      hyperreflectivity was thought to be due to calcium deposits. CONCLUSIONS: Angioid
      streaks were visualized more clearly and in larger numbers by ICG-A than FA.
      However, in some cases streaks that were funduscopically and fluorescein
      angiographically visible could not be seen by ICG-A. Occult CNV was detected by
      ICG-A. Some mottled areas were seen and more clearly visualized by ICG-A. Calcium
      deposits were observed as localized areas of hyperreflectivity on OCT. These
      findings indicate that fluorescein angiography, ICG-A and optical coherence
      tomography all provide supportive information for each other and can be used for
      either diagnosis or follow-up of those patients.

PMID- 12510717
TI  - Macular thickness measured by optical coherence tomography (OCT) in diabetic
      patients.
AB  - PURPOSE: 1) To compare macular thickness (MT) by optical coherence tomography
      (OCT) in diabetics and controls; 2) to assess the relationship between MT and
      stage of diabetic retinopathy (DR) and macular edema (ME); 3) to quantify MT
      changes after laser treatment for ME. METHODS: One-hundred and thirty-seven
      patients with diabetes mellitus (216 eyes) were admitted to the study and
      examined by stereo-color fundus photos, retinal fluorangiography and OCT. DR was
      classified as: 1) no DR (46 eyes: 21.3%); 2) background DR (66 eyes: 30.6%); 3)
      pre-proliferative DR (50 eyes: 23.1%); 4) proliferative DR (54 eyes: 25%). The
      study group was then divided into three ME groups: 1) no edema (65 eyes: 30.1%);
      2) not clinically significant ME (no CSME) (45 eyes: 20.8%); 3) clinically
      significant macular edema (CSME) (106 eyes: 49.1%). Three-month follow-up
      tomograms were taken to evaluate eyes laser-treated only for ME. The control
      group consisted of 50 eyes of 50 non-diabetic, age- and sex-matched subjects.
      RESULTS: MT was 369.3 +/- 163.2 microm in diabetics and 161.9 +/- 12.9 microm in
      controls (p < 0.001). In the four DR groups it was: 1) 211.0 +/- 37.6 microm; 2)
      370.8 +/- 159.6 microm; 3) 419.1 +/- 138.2 microm; 4) 456.1 +/- 162.0 microm
      (p<0.001). In the three ME groups, MT was: 1)227.8 +/- 53.4 microm; 2) 321.8 +/-
      124.2 microm; 3) 476.2 +/-146.6 microm (p < 0.001). In the 52 eyes treated with
      laser photocoagulation of the posterior pole only and with a follow-up > 3
      months, MT before and after treatment was 468.2 +/- 83. 17 microm and 372.1 +/-
      120.63 microm. CONCLUSIONS: MT was greater in diabetics than controls and tended
      to increase with DR and ME severity. OCT is a sensitive technique for detecting
      early diabetic macular abnormalities and quantifying their reduction after laser
      treatment.

PMID- 12510718
TI  - Hyperhomocysteinemia and retinal vascular occlusive disease.
AB  - PURPOSE: Elevated plasma homocysteine is an independent risk factor for
      thrombosis and vascular disease. This prospective study compared plasma total
      homocysteine levels in patients with retinal vascular occlusive disease and in
      matched healthy controls. METHODS: We measured plasma total homocysteine in 56
      consecutive patients with recently diagnosed retinal vascular occlusive disease:
      36 had central retinal vein occlusion, 12 branch retinal vein occlusion, and 8
      retinal artery occlusion, and compared them with 59 age- and sex-matched healthy
      controls. Homocysteine levels were determined by high-performance liquid
      chromatography with electrochemical detection. Hyperhomocysteinemia was defined
      as a plasma homocysteine level above the 95th percentile in the control group
      (13.6 micromol/L). RESULTS: Mean plasma total homocysteine levels were
      significantly higher in patients than controls (16.1 +/- 8.3 vs. 8.96 +/- 5.6
      micromol/L p < 0.001). Mean homocysteine levels were significantly higher in the
      retinal vein occlusion and retinal artery occlusion groups than the control group
      (15.3 +/- 8.2 and 20.95 +/- 6.9 vs 8.96 +/- 5.6 micromol/L, p < 0.001). Estimates
      of the relative risk indicated that the risk of hyperhomocysteinemia was
      significantly higher in patients with retinal vascular occlusive disease than
      controls. Hyperhomocysteinemia was present in 37 (66.1%) of the 56 patients with
      retinal vascular occlusive disease but only 2 (3.4%) controls (odds ratio [OR]
      47.5, 95% confidence interval [CI] 9.8-149.9). Hyperhomocysteinemia was present
      in 29 (60.4%) of the patients with retinal vein occlusion (OR 43.5, 95% CI 8.77
      141.93) and in 6 (75%) patients with retinal artery occlusion (OR 85.5, 95% CI
      7.49-1,173.1). CONCLUSIONS: High plasma homocysteine is a risk factor for retinal
      vascular occlusive disease so it may be useful to measure homocysteine in the
      management of these patients. A randomized, controlled trial is required to study
      the effect of lowering with homocysteine folic acid and other B vitamins on the
      risk of recurrent vascular occlusion in the same eye or its development in the
      fellow eye.

PMID- 12510719
TI  - Selective photocoagulation in Coats' disease: ten-year follow-up.
AB  - PURPOSE: The diagnostic hallmark of Coats' disease is development of "light bulb"
      telangiectasis in the retinal periphery, leading to posterior pole intraretinal
      and subretinal exudation. Even after complete obliteration of all abnormal
      vessels and resorption of all exudates, follow-up examinations are mandatory for
      several years. METHODS: We retrospectively analyzed the charts, pictures and/or
      fluorescein angiographies of a series of 32 consecutive patients, in which the
      diagnosis of Coats' disease was made. All patients underwent selective
      photocoagulation of the telangiectasis using a yellow-dye laser. Efficacy of
      treatment was monitored with drawings and/or fluorescein angiographies. RESULTS:
      All our patients had unilateral disease, with macular involvement and exudative
      retinal detachment. Visual acuity improved in one patient, decreased from light
      perception to blindness in another, and was unchanged in the remainder.
      CONCLUSIONS: This is the first report of anatomical benefits from treatment with
      a yellow-dye laser (i.e., selective photocoagulation without cryotherapy or
      drainage) despite the presence of a severe form of Coats' disease. Our young
      Coats' patients responded quickly to treatment. With successful obliteration of
      the abnormal vasculature, exudates began to absorb in about 4 to 8 weeks
      although, in some cases, 10 to 12 months were needed to obtain resolution of the
      exudative detachment. Poor visual outcome of 20/100 or worse was common. In
      Coats' patients, the key issue is continuous control and long-term follow-up.

PMID- 12510720
TI  - Retinopathy of prematurity and other ocular problems in premature infants
      weighing less than 1500 g at birth.
AB  - PURPOSE: To estimate the incidence of retinopathy of prematurity and other ocular
      problems in a population of preterm infants. METHODS: This retrospective study
      included all infants with gestational age (GA) <32 weeks and birth weight (BW)
      <1500 g cared for in the neonatal intensive care unit (NICU) over a period of
      nine years (1992-2000). Ophthalmological examination was started the 4th week of
      life and included refractive examination, examination of the cornea and
      funduscopy under mydriasis. An ocular motility test was done after the 2nd month.
      RESULTS: The study included 194 infants. Stage I and II retinopathy occurred in
      51 infants but regressed spontaneously. Five of the 194 (2.5%) had to undergo
      cryopexy. Optic disc atrophy was observed in association with peri
      intraventricular hemorrhage (PIIVH) (grade IV) in seven infants. Fifteen infants
      (7.7%) had retinal hemorrhages which were absorbed by three months of age. Almost
      20% of the study infants developed high refractive errors and 13.4% strabismus.
      CONCLUSIONS: Not only retinopathy of prematurity, but other serious ocular
      problems were observed in this population of preterm infants. The role of PIIVH
      III-IV in the pathogenesis of certain ocular problems needs further elucidation.

PMID- 12510721
TI  - Our experience with perfluorohexyloctane (F6H8) as a temporary endotamponade in
      vitreoretinal surgery.
AB  - PURPOSE: To evaluate the use of F6H8 as a temporary endotamponade for complicated
      and special cases of retinal detachment instead of silicone oil. METHODS: We have
      used F6H8 with 14 patients since February 1999. Eight suffered from
      rhegmatogenous retinal detachment (RRD) with multiple tears located inferiorly.
      Three presented inferior traction retinal detachment (TRD) under silicone oil,
      two suffered from ocular trauma with inferior TRD, and one had idiopathic macular
      hole. The substance was introduced into the eye after pars plana vitrectomy and
      membrane peeling if needed, and we tried to introduce as much as possible.
      RESULTS: With F6H8 the retina was easily reattached in all cases, like with
      perfluorocarbon liquids. The postoperative view was very good. F6H8 was removed
      in all cases after 3-8 weeks. Anatomical success was achieved in 12 out of 14
      eyes. Two eyes presented severe PVR. F6H8 entered the anterior chamber in 4
      cases, but no corneal complications occurred. In one case there was a marked IOP
      rise due to an anterior block, treated with superior iridotomy. In two cases
      retinal detachment (RD) occurred in the upper part and was treated with
      additional surgery, F6H8 removal and silicone oil injection. CONCLUSIONS: F6H8
      seems to be a promising tamponade agent for special cases of RD.

PMID- 12510722
TI  - Outcomes of surgical (pars plicata and limbal lensectomy, vitrectomy) and non
      surgical management of persistent fetal vasculature (PFV): an analysis of 54
      eyes.
AB  - PURPOSE: To identify clinical characteristics associated with outcomes of
      treatment for persistent fetal vasculature (PFV based on a modified
      classification. METHODS: In this noncomparative case series, 54 eyes of 47
      consecutive patients with PFV managed from 1981 until 1998 at a tertiary eye
      hospital were reviewed. Pars plicata lensectomy and vitrectomy was performed in
      34 eyes and translimbal lensectomy and vitrectomy in five. Fifteen eyes were
      managed non-surgically. The following outcomes were measured: 1) "Visual
      improvement", defined as at least one Zipf's category improvement of best
      corrected final vision as compared with initial visual acuity, provided that
      final vision of CSUM (central, steady, unmaintained) equal to 20/100-20/30 was
      obtained. 2) "Cosmetic acceptability", defined as the absence of the following:
      small orbit, externally small appearing eye with microcornea and hypotony, eye
      deviation more than 35 prism diopters without strabismus surgery and corneal
      opacity. RESULTS: Six eyes were inoperable. In 10 out of 33 operated eyes (30.3%)
      improvement of vision was obtained including four eyes with an anterior form and
      six eyes with a combined form of PFV. In univariate analysis, factors such as
      anterior form of PFV surgery in the combined form and having a normal retina, had
      a weak association with a higher chance of visual improvement. In multivariate
      regression analysis the likelihood of unacceptable cosmetic appearance was higher
      in females than males (OR = 10.5), and in bilateral cases (OR = 7.9). Offspring
      of consanguineous marriages had more severe forms of PFV. CONCLUSIONS: Although
      visual potential is limited in PFV some eyes with an anterior or combined form
      and normal retina achieved improvement of visual acuity after surgery. However,
      statistically no single factor except sex and bilateral PFV (for cosmetic
      unacceptability) reliably predicted the results of treatment. Therapy should be
      individualized based on clinical findings. Genetic studies in offspring of
      consanguineous marriages with PFV may prove informative.

PMID- 12510723
TI  - Perfluorohexyloctane endotamponade for treatment of subfoveal hemorrhage.
AB  - PURPOSE: To report on the use of perfluorohexyloctane as a heavy liquid to
      temporarily tamponade the fovea for the prevention of recurrent massive subfoveal
      hemorrhage in patients with exudative age-related macular degeneration (ARMD).
      METHODS: The case series comprised seven patients with acute massive subfoveal
      hemorrhage due to exudative ARMD. The patients underwent pars plana vitrectomy,
      drainage of the subretinal blood, and foveal endotamponade with
      perfluorohexyloctane. The perfluorohexyloctane was removed 80.4 +/- 38.1 days
      (median 98 days; range 22-118 days) after the primary surgery in a second pars
      plana intervention. RESULTS: In six patients (85.7%) the subretinal hemorrhage
      removed during the first pars plana vitrectomy did not recur after removal of
      perfluorohexyloctane. In the seventh, however, a subretinal hemorrhage re
      developed five days after release of perfluorohexyloctane. No large epiretinal
      membranes were observed. In six eyes (85.7%), the retina remained attached after
      removal of perfluorohexyloctane but in one eye proliferative vitreoretinopathy
      developed, with central retinal detachment. After the first pars plana
      vitrectomy, visual acuity increased slightly but not significantly (p = 0.25),
      from 0.03 +/- 0.03 to 0.05 +/- 0.07. Intraocular pressure rose from 15.0 +/- 1.9
      mm Hg to 24.9 +/- 16.9 mm Hg. After a follow-up of 69.7 +/- 121.0 days after
      removal of the perfluorohexyloctane, final visual acuity was 0.02 +/- 0.04.
      CONCLUSIONS: Perfluorohexyloctane may be a useful additional tool for preventing
      the recurrence of subfoveal re-bleeding in exudative ARMD.

PMID- 12510724
TI  - Ladies with Leber's hereditary optic neuropathy: an atypical disease.
AB  - PURPOSE: Leber's Hereditary Optic Neuropathy (LHON) is considered to be a disease
      predominantly affecting young males. The risk of women becoming symptomatic if
      they are carriers of a primary mutation is 1/5 of that in males. The disease
      however appears to behave differently in women in some instances. We describe
      three cases of ladies with LHON and discuss the importance of making the
      diagnosis. CASE REPORTS: A 28-year-old female presented with blurring of vision
      in her left eye with bilateral small hyperemic discs and telangiectatic vessels
      adjacent to them. DNA analysis confirmed the 11778 mutation and the second eye
      remains unaffected 10 years later. The second case was 49 years old and presented
      with bilateral visual loss developing over 3 months. She had no family history of
      visual loss but had a past history of Wolf Parkinson White syndrome and 3460
      mutation was confirmed. The last case was diagnosed with multiple sclerosis at
      age 24 and went on to develop visual loss with poor recovery. DNA analysis
      demonstrated the 11778 mutation and confirmed LHON. CONCLUSIONS: All three cases,
      although not unique, posed considerable diagnostic difficulties over a long
      period of time. The authors have highlighted important associations of the
      disease and stress the importance of making the diagnosis in women. They are at
      increased risk of having affected children, unlike the affected males, especially
      if they are affected themselves and may wish to seek further genetic advice.

PMID- 12510725
TI  - Retinal vein occlusion in lymphomatoid papulosis.
AB  - PURPOSE: To describe an unusual patient who presented with hemi-retinal vein
      occlusion and lymphomatoid papulosis (LyP). METHODS: Clinicopathological case
      study. RESULTS: A 42 year old female patient presented with blurring of vision in
      her left eye and a nodular eruption of the skin involving arms, face and torso.
      She also complained of a non-itchy, blotchy rash on the arms, face and torso
      lasting for period of three months. Ocular examination showed a left superior
      hemi-retinal vein occlusion. The nodules resolved spontaneously over a period of
      two-three weeks leaving a faint scar. Hematological and systemic evaluation for
      auto-immune disorders, hypercoagulability, systemic malignancy and lymphoma were
      negative. A biopsy of the skin nodule was performed which showed infiltration of
      lymphoid blast cells which were CD30 positive. Based on the clinicopathological
      features a diagnosis of lymphomatoid papulosis (LyP) was made. CONCLUSIONS:
      Clinical and pathological features of this patient may suggest the retinal vein
      occlusion may be secondary to LyP.

PMID- 12510726
TI  - Ipsilateral orbital cavernous hemangioma and choroidal hemangioma.
AB  - PURPOSE: A unique case of simultaneous ipsilateral choroidal and orbital
      hemangiomas is described. METHODS: A 71-year-old man was found to have a left
      orbital intraconal mass while being worked up for intractable headache. He also
      had a left juxtapapillary choroidal hemangioma which did not cause any leakage to
      macular area. RESULTS: The left intraconal tumor was removed by medial
      transconjunctival orbitotomy. Histopathological examination revealed cavernous
      hemangioma. The ipsilateral choroidal hemangioma was managed by observation only.
      During 15 months of follow-up, there has been no growth or accumulation of
      subretinal fluid. CONCLUSIONS: The occurrence of orbital cavernous and choroidal
      hemangiomas on the same side suggests common pathogenic derangement acting on two
      different sites.

PMID- 12510727
TI  - Retinochoroidal mass: a presenting feature of metastatic oat cell carcinoma of
      lung.
AB  - Ocular metastasis from lung carcinoma is a well recognised phenomenon. Rarely
      metastasis can be the presenting feature with no evidence of any systemic
      malignancy. We present a case of retinochoroidal mass in a patient who was
      subsequently diagnosed as having small cell carcinoma of the lung.

PMID- 12510728
TI  - Management of scleral rupture during retinal detachment surgery: a case report.
AB  - PURPOSE: Rupture of the sclera occurring during retinal detachment surgery is
      generally associated with unfavourable anatomic and visual outcomes. Re-operation
      after a failed scleral buckle procedure and pre-existing scleral thinning are
      considered the main risk factors for scleral rupture. CASE REPORT: We describe
      the management and the favourable outcome of a case of scleral rupture in a 71
      year-old woman during re-operation for retinal detachment. CONCLUSIONS: We
      managed this case of scleral rupture in accordance with current indications
      concerning the anatomical recovery, by scleral suture and patch graft, restoring
      IOP by gas tamponade. The positive outcome was partly related to the prompt
      closure of the retinal hole which led to reattachment, and partly to favourable
      events such as the moderate intensity of vitreous hemorrhage and the lack of any
      more serious intraoperative and postoperative complications.

PMID- 12510729
TI  - New findings in the Parry-Romberg syndrome: a case report.
AB  - PURPOSE: To describe further findings in the Parry-Romberg syndrome that might
      contribute towards a better understanding of the disease. DESIGN: Case report.
      METHODS: The clinical history of a patient with the Parry-Romberg syndrome was
      studied, and fluorangiography and echography were carried out. RESULTS: Clinical
      observation revealed classic hemifacial atrophy; fluorescein angiography showed
      telangiectasis, light staining of the retina, and leakage from the largest
      telangiectasis and the optic disc vessels; echography showed shrinkage of the
      eyeball and thinning of the extraocular muscles. CONCLUSIONS: Enophthalmos in
      this disease is caused not only by progressive fat atrophy but also by shrinkage
      of the eyeball and thinning of the extraocular muscles; the shrinkage of the
      eyeball helps explain the presence of choroidal and retinal folding and
      hyperopia, confirming the primary involvement of connective tissue in this
      disease.

PMID- 12510730
TI  - A cell-based bar code reader for high-throughput screening of ion channel-ligand
      interactions.
AB  - This paper presents a microfluidics-patch clamp platform for performing high
      throughput screening and rapid characterization of weak-affinity ion channel
      ligand interactions. This platform integrates a microfluidic chip consisting of
      multiple channels entering an open volume with standard patch clamp equipment.
      The microfluidic chip is placed on a motorized scanning stage and the method
      relies on the ability to scan rapidly, on the order of milliseconds, a patch
      clamped cell across discrete zones of different solutions created in the open
      volume. Under ideal conditions, this method has the capacity to obtain
      kinetically resolved patch clamp measurements and dose-response curves of up to
      10(3) ligand solutions in a single day.

PMID- 12510731
TI  - Autonomous microfluidic capillary system.
AB  - The transport of minute amounts of liquids using microfluidic systems has opened
      avenues for higher throughput and parallelization of miniaturized bio/chemical
      processes combined with a great economy of reagents. In this report, we present a
      microfluidic capillary system (CS) that autonomously transports aliquots of
      different liquids in sequence: liquids pipetted into the service port of the CS
      flow unidirectionally through the various sections of the CS, which comprises a
      15-pL reaction chamber, into the capillary pump. A CS can thus be operated by
      simply delivering the different samples to its service port. The liquid transport
      concept presented here is advantageous because the pumping and valving functions
      are integrated into the device by means of capillary phenomena, and it therefore
      does not require any external power supply or control device. Thus, arrays of CSs
      can easily be formed by cloning a functional CS. Alternatively, the flow of
      liquids in CSs can also be interactively tuned if desired by (i) forcing the
      evaporating of liquid out of the capillary pumps and (ii) by contacting a
      secondary, removable capillary pump to the embedded ones. We illustrate the
      possibilities of CSs by conducting a surface immunoassay for a cardiac marker,
      within 25 min, on an area of 100 x 100 microm2, using 16 sequential filling
      steps.

PMID- 12510732
TI  - Miniature cylindrical ion trap mass spectrometer.
AB  - A miniature cylindrical ion trap mass spectrometer is described, and preliminary
      data are presented. Functionality and performance of laboratory-scale instruments
      have been maintained to the extent possible in this battery-operated mass
      spectrometer. Capabilities include tandem mass spectrometry experiments. Custom
      designed electronic components include the RF scanning and amplification system,
      data acquisition components, and lens power supplies, as well as a custom
      software application. Direct leak and membrane introduction inlet systems are
      used for sample introduction. A mass/charge range of approximately 250 Th with
      unit mass resolution has been demonstrated.

PMID- 12510733
TI  - Analytical performance of a miniature cylindrical ion trap mass spectrometer.
AB  - The analytical performance of a fieldable cylindrical ion trap (CIT)-based
      miniature mass spectrometer is described. A detailed description of the
      instrument itself is to be found in the immediately preceding paper (Patterson,
      G. E.; Guymon, A. J.; Riter, L S.; Everly, M.; Griep-Raming, J.; Laughlin, B. C.;
      Ouyang, Z.; Cooks, R. G., Miniature Cylindrical Ion Trap Mass Spectrometer, Anal.
      Chem. 2002, 24, 6145-6153). Applications employing the MS/MS and MSn capabilities
      of the miniature instrument and analytical performance criteria are given here.
      The limit of detection for methyl salicylate, introduced as the pure vapor, is
      estimated as 1 pg. The resolution, R = m/delta m, where delta m, measured as full
      width at half-maximum, is estimated as 100. Monitoring of organic compounds in
      air is performed using a permeation membrane introduction device coupled to the
      mass spectrometer. Water monitoring is performed using an external membrane
      introduction mass spectrometry (MIMS) system, with acetophenone and toluene
      serving as model compounds. Data are given for chemical warfare agent simulants,
      methyl salicylate, and dimethyl methyl phosphonate (DMMP) in air. On-line
      detection of menthol vapor emitted from a cough drop is reported. Methyl
      salicylate in air gives a recognizable mass spectrum at 400 ppb in the ambient
      system, while use of a heated membrane brings the detection limit down to 10 ppb.

PMID- 12510734
TI  - DNA damage detection technique applying time-resolved fluorescence measurements.
AB  - A novel DNA damage detection technique based on the characteristic fluorescence
      lifetimes exhibited by Pico-Green-single-stranded DNA and -double-stranded DNA
      complexes is employed to establish the damage produced on DNA isolated from sheep
      white blood cells following gamma radiation. This technique, which incorporates
      key concepts such as alkaline unwinding buffers and higher unwinding rates of
      damaged DNA compared to undamaged DNA, allows for the differentiation of DNA
      damage resulting from doses of gamma radiation in the 0-100-Gy range, with the
      potential of analyzing samples consisting of as little as 10(4) cells.
      Experiments were carried out using commercial DNA sources as well as DNA isolated
      from sheep white blood cells, suggesting its potential for use with isolated DNA
      from virtually any eukaryotic cell.

PMID- 12510735
TI  - Nanochannels on a fused-silica microchip and liquid properties investigation by
      time-resolved fluorescence measurements.
AB  - We have fabricated nanometer-sized channels, demonstrated a technique for the
      introduction of liquid into the channels, and carried out time-resolved
      fluorescence measurements of aqueous solutions. In this study, 330-nm- and 850-nm
      sized channels were fabricated on fused-silica substrates by fast atom beam
      etching and hydrofluoric acid bonding methods. A liquid introduction method
      utilizing capillary action was demonstrated. The liquid introduction was observed
      under an optical microscope, and the liquid velocity during the introduction was
      analyzed by surface energy and macroscale hydrodynamics. The liquid velocity due
      to capillary action in the nanometer-sized channel seemed more than four times
      slower than the estimation. Then, aqueous solutions of rhodamine 6G (R6G),
      sulforhodamine 101 (SR101), and rhodamine B (RB) in the channels were measured by
      time-resolved fluorescence spectroscopy; spectra of the same solution in a 250
      microm-sized channel were also measured as a reference for the macrospace.
      Although the fluorescence spectra in the 330-nm-, 850-nm- and 250-microm-sized
      channels agreed with one another, the fluorescent decays in the nanometer-sized
      channels were faster for R6G and SR101 and slower for RB than the respective
      decays in the 250-microm-sized channels. The results suggested the solutions had
      lower dielectric constants and higher viscosities in the nanometer-sized
      channels.

PMID- 12510736
TI  - Multianalyte pin-printed biosensor arrays based on protein-doped xerogels.
AB  - We report the first biosensor arrays based on pin printing protein-doped
      xerogels. The individual biosensor elements are on the order of 100 microm in
      diameter. Arrays are formed (1) onto a planar substrate that is excited by an
      external source (laser) or (2) directly on the face of a light-emitting diode. We
      illustrate the potential of our approach by fabricating, testing, and
      characterizing four types of pin-printed biosensor arrays (PPBSA) for the
      simultaneous detection of glucose and O2. The analytically reliable operating
      ranges for the PPBSAs are 0.1-10 mM for glucose and 0.1-100% for O2. The PPBSAs
      exhibit short- and long-term reproducibilities of no worse than 4 and 8%,
      respectively. The overall array-to-array response reproducibilities are < or =
      12%. These results demonstrate for the first time the combination sol-gel
      processing and pin printing methods as a way to rapidly form ensembles of
      integrated, reusable, and stable biosensor arrays for simultaneous multianalyte
      detection.

PMID- 12510737
TI  - Internal energy of ions generated by matrix-assisted laser desorption/ionization.
AB  - To provide an objective measure of the correlation between the internal energy
      content of ions generated by matrix-assisted laser desorption/ionization (MALDI)
      and the matrix properties, a series of well-characterized benzyl-substituted
      benzylpyridinium salts were used as thermometer molecules (TMs). To determine the
      internal energy variations of analyte ions, the survival yields of TM molecular
      ions were measured in three different matrixes, alpha-cyano-4-hydroxycinnamic
      acid (CHCA), 3,5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid, SA), and 2,5
      dihydroxybenzoic acid (DHB). Statistical analysis of extensive survival yield
      data indicated that there were discernible differences among the studied
      matrixes. The experimental survival yields of the TM ions were used to calculate
      the unimolecular decomposition rate coefficient. Corresponding theoretical
      reaction rate coefficients were calculated based on the Rice-Ramsperger-Kassel
      Marcus (RRKM) theory for different internal energies of the TMs. The internal
      energies of the ions were obtained by projecting the experimental rate
      coefficient values onto the theoretical curves obtained by the RRKM calculations.
      Molecular ions of the analytes showed decreasing survival yields and consequently
      increasing internal energies in the three matrixes in the following order: CHCA,
      SA, and DHB with "cold", "intermediate", and "hot" characteristics, respectively.
      Qualitatively, this could be interpreted as a significant departure from earlier
      observations suggesting an opposite trend. The classification as hot and cold
      matrixes should be further qualified by accounting for the influence of laser
      pulse energy and the nature of the analyte. Higher laser pulse energy led to an
      elevated level of energy transferred to the analyte, which in turn resulted in a
      diminished survival yield of the analyte molecular ion. It is quite possible that
      the assignment of hot and cold reverses as the analyte or the laser energy
      changes. These findings can help predict the outcome of postsource decay
      experiments and clarify the concept of hot and cold matrixes in MALDI mass
      spectrometry.

PMID- 12510738
TI  - Analysis of microbial mixtures by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - Many different laboratories are currently developing mass-spectrometric
      techniques to analyze and identify microorganisms. However, minimal work has been
      done with mixtures of bacteria. To demonstrate that microbial mixtures could be
      analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS), mixed bacterial cultures were analyzed in a double-blind fashion. Nine
      different bacterial species currently in our MALDI-MS fingerprint library were
      used to generate 50 different simulated mixed bacterial cultures similar to that
      done for an initial blind study previously reported (Jarman, K. H.; Cebula, S.
      T.; Saenz, A. J.; Petersen, C. E.; Valentine, N. B.; Kingsley, M. T.; Wahl, K. L.
      Anal. Chem. 2000, 72, 1217-1223). The samples were analyzed by MALDI-MS with
      automated data extraction and analysis algorithms developed in our laboratory.
      The components present in the sample were identified correctly to the species
      level in all but one of the samples. However, correctly eliminating closely
      related organisms was challenging for the current algorithms, especially in
      differentiating Serratia marcescens, Escherichia coli, and Yersinia
      enterocolitica, which have some similarities in their MALDI-MS fingerprints.
      Efforts to improve the specificity of the algorithms are in progress.

PMID- 12510739
TI  - Sample depletion of the matrix-assisted laser desorption process monitored using
      radionuclide detection.
AB  - To investigate analyte consumption during the laser desorption process, matrix
      assisted laser desorption/ionization mass spectrometry (MALDI MS) is combined
      with radionuclide detection. Radionuclide detection provides highly sensitive and
      quantitative information on the amount of radiolabeled analytes in a MALDI MS
      sample spot. 14C-Labeled cytochrome c is deposited with 2,5-dihydroxybenzoic acid
      in 10-nL volume spots. By comparing radioactivity levels of the labeled
      cytochrome c both before and after spectral acquisition, the reduction in labeled
      analyte molecules on the target allows monitoring of the moles of desorbed
      sample. Through a depletion study on this sample, the amount of analyte consumed
      for MALDI time-of-flight spectral acquisition and the average number of molecules
      desorbed per laser ablation are determined. When [14C]-cytochrome c is no longer
      detected by MALDI MS, approximately 70% of the original analyte remains in the
      sample spots. Redissolving the spots produced further desorption, indicating that
      the analyte before dissolution was in a physical environment that did not
      facilitate the desorption process. As a technique with a response that does not
      depend on the environment of the analyte, radionuclide detection allows
      characterization of mass-limited sampling methods to better understand the MALDI
      process.

PMID- 12510740
TI  - Finite element simulation of pinched pressure-driven flow injection in
      microchannels.
AB  - A pinched pressure-driven flow injection on a microchip is numerically simulated
      in order to optimize the relative values of the operational parameters. The
      geometry studied is a two-dimensional rectangular channel featuring a cross
      junction with a large depth-over-width ratio. The hydrodynamic and convection
      diffusion equations are solved for the two steps of the process: first, the
      sample solution is pinched into the transversal channel (injection channel), and
      then it is injected into the longitudinal one (separation channel), where the
      time evolution of the concentration is analyzed for different types of the
      detectors. Electroosmotic flow calculations have also been performed and have
      shown a good agreement with literature. The results for pressure-driven flow
      point out that the shape of the detection signal is strongly dependent on the
      velocity in the separation channel and on the position of the detection probes.
      The so-called double-humped peak, caused by the parabolic flow profile at high
      driving flow rate is analyzed. A tight pinch greatly decreases the amount of
      injected sample and, consequently, the signal sensitivity without increasing its
      quality. A proper pullback of the sample during the separation process can
      decrease the tailing due to the sample leakage from the injection channel.
      Although a high sample pullback causes a considerable decrease in the signal
      sensitivity, it also greatly enhances the peak resolution. Finally, it is shown
      that a wider injection channel with high sample pullback ensures an improved
      signal sensitivity with good resolution.

PMID- 12510741
TI  - Thin-layer chromatography and electrospray mass spectrometry coupled using a
      surface sampling probe.
AB  - A combined surface sampling probe/electrospray emitter was used for the direct
      readout of thin-layer chromatography plates by electrospray mass spectrometry.
      The technique was demonstrated with reversed-phase C18 plates using a three-dye
      mixture composed of methylene blue, crystal violet, and rhodamine 6G for positive
      ion mode detection and a separate dye mixture containing fluorescein, naphthol
      blue black, and fast green FCF for negative ion mode detection. Acquisition of
      mass spectra of components of individual bands on the plate was shown by manual
      stepping to and sampling from specific locations within the bands. Computer
      controlled scanning of development lanes on the plate was illustrated by using
      multiple ion monitoring in both positive and negative ion modes. Commercial TLC
      plates were used and no post-separation processing other than drying of the
      plates was required prior to mass spectrometric analysis. Readout resolution, the
      limits of scan speed, detection levels, TLC phase, and eluting solvents were
      investigated and discussed.

PMID- 12510742
TI  - Pressure-assisted capillary electrophoresis electrospray ionization mass
      spectrometry for analysis of multivalent anions.
AB  - We describe a method, based on pressure-assisted capillary electrophoresis
      coupled to electrospray ionization mass spectrometry (PACE/ESI-MS), that allows
      the simultaneous and quantitative analysis of multivalent anions, such as citrate
      isomers, nucleotides, nicotinamide-adenine dinucleotides, and flavin adenine
      dinucleotide, and coenzyme A (CoA) compounds. Key to the analysis was using a
      noncharged polymer, poly(dimethylsiloxane), coated to the inner surface of the
      capillary to prevent anionic species from adsorbing onto the capillary wall. It
      was also necessary to drive a constant liquid flow toward the MS by applying air
      pressure to the inlet capillary during electrophoresis to maintain a conductive
      liquid junction between the capillary and the electrospray needle. Although
      theoretical plates were inferior to those obtained by CE/ESI-MS using a cationic
      polymer-coated capillary, the PACE/ESI-MS method improved reproducibility and
      sensitivity of these anions. Eighteen anions were separated by PACE and
      selectively detected by a quadrupole mass spectrometer with a sheath-flow
      electrospray ionization interface. The relative standard deviations (n = 6) of
      the method were better than 0.6% for migration times and between 1.4% and 6.2%
      for peak areas. The detection limits for these species were between 0.4 and 3.7
      micromol/L with pressure injection of 50 mbar for 30 s (30 nL), that is, mass
      detection limits calculated in the range from 12 to 110 fmol at a signal-to-noise
      ratio of 3. The utility of the method was demonstrated by analysis of citrate
      isomers, nucleotides, dinucleotides, and CoA compounds extracted from Bacillus
      subtilis cells.

PMID- 12510743
TI  - Analysis of bromotryptophan and hydroxyproline modifications by high-resolution,
      high-accuracy precursor ion scanning utilizing fragment ions with mass-deficient
      mass tags.
AB  - Protein modifications are often detected by precursor ion scanning. When
      quadrupole TOF mass spectrometers are used for precursor ion scanning with high
      resolution, high-accuracy fragment ion selection, "reporter" ions are required to
      have a unique mass within +/-0.04 Da or less instead of +/-0.5 Da on triple
      quadrupole mass spectrometers, the traditional instrument used for precursor ion
      scanning. Thus, characteristic fragment ions can be utilized even if other
      fragment ions have the same nominal mass as long as the characteristic fragment
      ions are slightly mass deficient as compared to the other fragments, i.e., when
      they have an inherent mass-deficient mass tag. Here, the immonium ions of
      bromotryptophan and hydroxyproline are described as two fragment ions
      characteristic for tryptophan-brominated and proline-hydroxylated peptides,
      respectively. The "reporter" ion of trytophan-brominated peptides is highly mass
      deficient due to the presence of bromine, thereby allowing the selective
      detection of these species and the distinction from other dipeptidic a-, b-, and
      y-fragment ions by high-resolution, high-accuracy precursor ion scanning. This
      strategy also enables the differentiation between precursors giving rise to the
      oxygen-containing immonium ion of hydroxyproline and precursors of the immonium
      ions of near-ubiquitous leucine/isoleucine. Both immonium ions have the same
      nominal mass of 86 Da, but the exact masses differ by less than 0.04 Da. High
      resolution, high-accuracy precursor ion scanning enabled the identification of
      proline-hydroxylated and tryptophan-brominated species and the directed analysis
      of species carrying these modifications in a highly complex Conus textile
      conotoxin mixture. This lead to the characterization of one novel C. textile
      conotoxin containing a bromotryptophan residue and one novel C. textile conotoxin
      carrying two hydroxyproline residues.

PMID- 12510744
TI  - A quadrupole ion trap mass spectrometer with three independent ion sources for
      the study of gas-phase ion/ion reactions.
AB  - An instrument for the study of gas-phase ion/ion reactions in which three
      independent sources of ions, namely, two electrospray ionization sources and one
      atmospheric sampling glow discharge ionization source, are interfaced to a
      quadrupole ion trap mass analyzer is described. This instrument expands the scope
      of gas-phase ion/ion reaction studies by allowing for manipulation of the charge
      states of multiply charged reactant and product ions. Examples are provided
      involving the formation of protein-protein complexes in the gas phase. Complexes
      with charge states that cannot be formed from reactant ion charge states present
      in the normal electrospray charge state distributions can be formed in the new
      apparatus. Strategies that rely on both reactant ion charge state manipulation
      and product ion charge state manipulation are demonstrated. In addition,
      simplification of product ion spectra generated from dissociation of complexes
      formed via ion/ion reactions can be effected by using the discharge source to
      reduce the charge state of the product ions to primarily 1+.

PMID- 12510745
TI  - Retention of carbon and alteration of expected 13C-tracer enrichments by
      silylated derivatives using continuous-flow combustion-isotope ratio mass
      spectrometry.
AB  - Continuous-flow inlets from oxidation reactors are commonly used systems for
      biological sample introduction into isotope ratio mass spectrometers (IRMS) to
      measure 13C enrichment above natural abundance. Because the samples must be
      volatile enough to pass through a gas chromatograph, silylated derivatization
      reactions are commonly used to modify biological molecules to add the necessary
      volatility. Addition of a tert-butyldimethylsilyl (TBDMS) group is a common
      derivatization approach. However, we have found that samples do not produce the
      expected increment in measured 13C abundance as the TBDMS derivatives. We have
      made measurements of 13C enrichment of leucine and glutamate standards of known
      13C enrichment using derivatives without silicon (N-acetyl n-propyl ester), with
      silicon (TBDMS), and an intermediate case. The measurements of 13C in amino acids
      derivatized without silicon were as expected. The 13C enrichment measurements
      using the TBDMS derivative were higher than expected but could be corrected to
      produce the expected 13C enrichment measurement by IRMS if one carbon was removed
      per silicon. We postulate that the silicon in the derivative forms silicon
      carbide compounds in the heated cupric oxide reactor, rather than forming silicon
      dioxide. Doing so reduces the amount of CO2 formed from the carbon in the sample.
      Silylated derivatives retain carbon with the silicon and must be used carefully
      and with correction factors to measure 13C enrichments by continuous-flow IRMS.

PMID- 12510746
TI  - End-group analysis of blue light-emitting polymers using matrix-assisted laser
      desorption/ ionization time-of-flight mass spectrometry.
AB  - An analytical method based on matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS) has been applied to provide information
      on the structure of a copolymer, e.g., repeat unit and end group. Seven
      conjugated polymers, which have been demonstrated as the active component in blue
      light-emitting diodes, were synthesized through Suzuki polycondensation reaction
      in the presence of Pd(PPh3)4 catalyst. Their molecular weights were obtained
      using gel permeation chromatography analysis. MALDI-TOF MS was used to
      investigate the structure information in detail. The proposed end-group
      structures were confirmed by the identity between the observed and the simulated
      isotopic distribution of each polymer. The results demonstrate that these
      synthetic polymers possess various end groups and even contain macrocycles. The
      catalyst Pd(PPh3)4 was found to introduce phenyl end groups via aryl-aryl
      exchange between the catalytic palladium intermediate and the triphenylphosphine
      ligand. All these results are based on the analysis of the mass spectrum data,
      which suggests that MALDI-TOF MS is an extraordinarily strong tool in synthetic
      polymer structure analysis.

PMID- 12510747
TI  - Multiple open-channel electroosmotic pumping system for microfluidic sample
      handling.
AB  - The development of a novel, fully integrated, miniaturized pumping system for
      generation of pressure-driven flow in microfluidic platforms is described. The
      micropump, based on electroosmotic pumping principles, has a multiple open
      channel configuration consisting of hundreds of parallel, small-diameter
      microchannels. Specifically, pumps with microchannels of 1-6 microm in depth, 4
      50 mm in length, and an overall area of a few square millimeters, were
      constructed. Flow rates of 10-400 nL/min were generated in electric-field-free
      regions in a stable, reproducible and controllable manner. In addition, eluent
      gradients were created by simultaneously using two pumps. Pressures up to 80 psi
      were produced with the present pump configurations. The pump can be easily
      interfaced with other operational elements of a micrototal analysis system (micro
      TAS) device with multiplexing capabilities. A new microfluidic valving system was
      also briefly evaluated in conjunction with these pumps. The micropump was
      utilized to deliver peptide samples for electrospray ionization-mass
      spectrometric (ESI-MS) detection.

PMID- 12510748
TI  - Monte Carlo model of nonlinear chromatography: correspondence between the
      microscopic stochastic model and the macroscopic Thomas kinetic model.
AB  - The Monte Carlo model of chromatography is a description of the chromatographic
      process from a molecular (microscopic) point of view and it is intrinsically
      based on the stochastic theory of chromatography originally proposed by Giddings
      and Eyring. The program was previously validated at infinite dilution (i.e., in
      linear conditions) by some of the authors of the present paper. In this work, it
      has been further validated under nonlinear conditions. The correspondence between
      the Monte Carlo model and the well-known Thomas kinetic model (macroscopic
      model), for which closed-form solutions are available, is demonstrated by
      comparing Monte Carlo simulations, performed at different loading factors, with
      the numerical solutions of the Thomas model calculated under the same conditions.
      In all the cases investigated, the agreement between Monte Carlo simulations and
      Thomas model results is very satisfactory. Additionally, the exact correspondence
      between the Thomas kinetic model and Giddings model, when near-infinite dilution
      conditions are approached, has been demonstrated by calculating the limit of the
      Thomas model when the loading factor goes to zero. The model was also validated
      under limit conditions, corresponding to cases of very slow adsorption-desorption
      kinetics or very short columns. Different hypotheses about the statistical
      distributions of the random variables "residence time spent by the molecule in
      mobile and stationary phase' are investigated with the aim to explain their
      effect on the peak shape and on the efficiency of the separation.

PMID- 12510749
TI  - Chemiluminescence determination of chlorinated volatile organic compounds by
      conversion on nanometer TiO2.
AB  - A novel method based on conversion of chlorinated volatile organic compounds
      (CVOCs) to chlorine using a new type of column packed with nanometer TiO2 coupled
      with chemiluminescence (CL) has been developed for determination of them in
      workplace air. CVOCs are converted to chlorine by nanometer TiO2 at 220 degrees
      C. The Cl2 that is produced is selectively enriched on the column and
      subsequently released from the column at 600 degrees C. The Cl2 that is released
      is determined using a postcolumn CL detector. The CL intensity was linear with
      CCl4 in the range of 0.1-380 ppm, and the detection limit was 40 ppb (S/N = 3).
      Higher sensitivity could be acquired by using a larger volume of enrichment A
      similar procedure could be used for the determination of other CVOCs. CL
      intensities of CH2Cl2, CHCl3, and CCl4 at the same concentration increased in the
      order CH2Cl2 < CHCl3 < CCl4. The method has been successfully applied to the
      determination of CCl4 in workplace air, where 0.15-150 ppm CCl4 would be
      detected. The possible mechanism for the long lifetime of the column packed with
      nanometer TiO2 was tested using Raman spectrometer, X-ray powder diffraction,
      transmission electron microscopy and X-ray photoelectron spectroscopy. The
      results showed that the column packed with nanometer TiO2 could be operated in
      the reversible mode for determination of CVOCs under the present conditions. The
      method would be potentially applied to the analysis of other chlorinated
      compounds in environment, such as persistent organic pollutants.

PMID- 12510750
TI  - Sample preparation for quantitation of tritium by accelerator mass spectrometry.
AB  - The capability to prepare samples accurately and reproducibly for analysis of
      tritium (3H) content by accelerator mass spectrometry (AMS) greatly facilitates
      isotopic tracer studies in which attomole levels of 3H can be measured in
      milligram-sized samples. A method has been developed to convert the hydrogen of
      organic samples to a solid, titanium hydride, which can be analyzed by AMS. Using
      a two-step process, the sample is first oxidized to carbon dioxide and water. In
      the second step, the water is transferred within a heated manifold into a quartz
      tube, reduced to hydrogen gas using zinc, and reacted with titanium powder. The
      3H/1H ratio of the titanium hydride is measured by AMS and normalized to
      standards whose ratios were determined by decay counting to calculate the amount
      of 3H in the original sample. Water, organic compounds, and biological samples
      with 3H activities measured by liquid scintillation counting were utilized to
      develop and validate the method. The 3H/1H ratios were quantified in samples that
      spanned 5 orders of magnitude, from 10(-10) to 10(-15), with a detection limit of
      3.0 x 10(-15), which is equivalent to 0.02 dpm tritium/mg of material. Samples
      smaller than 2 mg were analyzed following addition of 2 mg of a tritium-free
      hydrogen carrier. Preparation of organic standards containing both 14C and 3H in
      2-mg organic samples demonstrated that this sample preparation methodology can
      also be applied to quantify both of these isotopes from a single sample.

PMID- 12510751
TI  - Evaporation and discharge dynamics of highly charged droplets of heptane, octane,
      and p-xylene generated by electrospray ionization.
AB  - We report studies of the evaporation and discharge dynamics of highly charged
      droplets generated by electrospray ionization from n-heptane, n-octane, and p
      xylene doped with Stadis-450, a conductivity-enhancing agent. A phase Doppler
      anemometer (PDA) characterizes individual droplets moving through the uniform
      electric field within an ion mobility cell according to size, velocity, and
      charge. Repeated reversal of the electric field allows multiple PDA measurements
      on selected droplets with diameters ranging from 3 to 60 microm and up to 10(7)
      elementary positive charges. This "ping-pong" technique provides individual
      droplet histories from which we determine the dynamics of solvent evaporation and
      charge loss. On average, n-heptane discharges at 101% of the Rayleigh limit of
      charge, while n-octane and p-xylene droplets discharge at 87% and 89% of their
      respective limits. Discharge events release an average of 19% of the charge in n
      heptane and 17% of the charge in both n-octane and p-xylene. Within the limits of
      the measurements, no detectable change in droplet diameter accompanies observed
      discharge events, indicating the loss of a relatively small fraction of the total
      volume. We compare these results to previous experiments, theoretical models for
      droplet evaporation and discharge, and predictions from the Rayleigh model. We
      report both Stadis-450 and triethylamine mass spectra in octane and discuss
      issues regarding the use of hydrocarbon solvents in electrospray mass
      spectrometry.

PMID- 12510752
TI  - Immunoaffinity purification and characterization of 4-hydroxy-2-nonenal- and
      malondialdehyde-modified peptides by electrospray ionization tandem mass
      spectrometry.
AB  - Two methods based on specific immunoaffinity enrichment followed by electrospray
      ionization (ESI) mass spectrometry (MS) have been developed for the specific
      analysis of 4-hydroxy-2-nonenal (HNE)- and malondialdehyde (MDA)-modified
      proteins (Michael and Schiff base adducts, respectively). Anti-HNE antibodies
      were immobilized on CNBr-activated sepharose, and the immunosorbent produced was
      used for the enrichment of HNE-adducted peptides originating from a model peptide
      modification and a tryptic digest of modified apomyoglobin. A further
      immunosorbent was produced by anti-dinitrophenyl immobilization and assayed for
      selective extraction of peptides modified with HNE and MDA that were initially
      converted to their respective hydrazones. Subsequent analysis and
      characterization of the different purified fractions by ESI-MS (MS/MS) revealed
      that the two immunosorbents enable efficient and specific enrichment of the
      carbonyl adducted proteins. This approach lowers substantially the detection
      limit of such modifications and, thus, enables better assessment and
      characterization of carbonyl modifications in biological and food systems.

PMID- 12510753
TI  - Effect of signal interference from dosing excipients on pharmacokinetic screening
      of drug candidates by liquid chromatography/mass spectrometry.
AB  - The effect of dosing vehicle excipients such as PEG400, propylene glycol, Tween
      80, and hydroxypropyl-beta-cyclodextrin on the accuracy of LC/MS measurements
      used in pharmacokinetic studies is examined. Using PEG400 as a probe compound,
      the concentration-time profile of the excipient in plasma from rats dosed both
      orally and intravenously is determined. These excipient plasma concentrations can
      result in a 2-5-fold increase in calculated plasma clearance values when the
      excipient interferes with the quantitation of the dosed compound. This can result
      in false rejection of a compound in a drug discovery screen. Several plasma
      purification methods and enhanced chromatographic selectivity are examined as
      ways to minimize or avoid excipient effects, particularly for very polar
      compounds. The combination of efficient sample purification and selective
      chromatography provides an effective way to diminish the significant interference
      effects of PEG400 and Tween 80. When appropriate, using negative ion mode MS or
      changing a dosing vehicle excipient, such as substituting propylene glycol for
      PEG400, provides an alternative approach for eliminating signal interference. The
      mechanism of excipient-related signal interference is discussed in relation to
      both competition of gas-phase proton-transfer reactions and high viscosity of
      dosing excipients.

PMID- 12510754
TI  - Poisson and multinomial mixture models for multivariate SIMS image segmentation.
AB  - Multivariate statistical methods have been advocated for analysis of spectral
      images, such as those obtained with imaging time-of-flight secondary ion mass
      spectrometry (TOF-SIMS). TOF-SIMS images using total secondary ion counts or
      secondary ion counts at individual masses often fail to reveal all salient
      chemical patterns on the surface. Multivariate methods simultaneously analyze
      peak intensities at all masses. We propose multivariate methods based on Poisson
      and multinomial mixture models to segment SIMS images into chemically homogeneous
      regions. The Poisson mixture model is derived from the assumption that secondary
      ion counts at any mass in a chemically homogeneous region vary according to the
      Poisson distribution. The multinomial model is derived as a standardized Poisson
      mixture model, which is analogous to standardizing the data by dividing by total
      secondary ion counts. The methods are adapted for contextual image segmentation,
      allowing for spatial correlation of neighboring pixels. The methods are applied
      to 52 mass units of a SIMS image with known chemical components. The spectral
      profile and relative prevalence for each chemical phase are obtained from
      estimates of model parameters.

PMID- 12510755
TI  - An absorption-based surface plasmon resonance sensor applied to sodium ion
      sensing based on an ion-selective optode membrane.
AB  - A surface plasmon resonance (SPR) sodium ion sensor using an ion optode membrane
      film was experimentally and theoretically described based on an absorption-based
      SPR principle proposed in our previous article (Kurihara, K; Suzuki, K. AnaL
      Chem. 2002, 74, 696-701). The sodium ion concentrations from 10(-6) to 10(-1)
      have been successfully determined not only by the resonance angle diagnosis of
      the SPR curve but also by the minimum reflectance one. The ion optode film was
      plasticized poly(vinyl chloride) including a neutral sodium ionophore, a pH
      sensitive cationic dye, and an anionic additive. Its optical absorption intensity
      changed with the sodium ion concentrations. The SPR ion sensor physically
      measured the complex refractive index caused by the absorption in the ion optode
      film. We have exhaustively investigated the experimental response behavior of the
      SPR curve relative to the sodium ion concentrations by comparison with
      numerically simulated SPR curves using a three-layer Fresnel equation including
      experimental values for the sodium ion optode membrane film. As predicted by the
      absorption-based SPR principle, the SPR curve behavior of the SPR ion sensors
      depended on two factors: one was the relation between the excitation frequency of
      the light source and the absorption maximum frequency in the ion optode film
      while the other was the gold metallic thickness in the Kretchmann configuration.
      The concept and practical theory of an absorption-based SPR sensor not only have
      been proved by the experimental results of the SPR sodium ion sensor but also
      have successfully allowed flexible ion sensing in an SPR sensor, which would be
      very difficult without the absorption mechanism in the ion optode film.

PMID- 12510756
TI  - Dynamics of single-protein molecules at a liquid/solid interface: implications in
      capillary electrophoresis and chromatography.
AB  - The behavior of individual molecules of R-phycoerythrin (RPE) was monitored by
      fluorescence imaging at various pHs and ionic strengths within the evanescent
      field layer (EFL) at a water/fused-silica interface. Above the isoelectric point
      (pI), the individual protein molecules moved between exposures with random
      motion. As the pH approached the pI of the protein, the RPE molecules were
      partially adsorbed onto the fused-silica surface. The residence time and the
      number of molecules within the EFL also increased near the pI. Below the pI, the
      protein molecules were completely and permanently adsorbed onto the surface.
      However, the observed number of distinct molecule spots was decreased somewhat
      because of aggregation. At a given buffer condition, plots of residence times and
      molecule numbers exhibit asymmetry nearly identical to the corresponding elution
      peaks of the proteins in capillary electrophoresis and capillary liquid
      chromatography. These results provide insights into the fundamental interactions
      for the adsorption/desorption of proteins at the liquid/solid interface.

PMID- 12510757
TI  - Scanning electrochemical microscopy of living cells. 4. Mechanistic study of
      charge transfer reactions in human breast cells.
AB  - Scanning electrochemical microscopy (SECM) has recently been employed for probing
      the redox properties of individual mammalian cells. It was shown that
      intracellular redox activity can be probed noninvasively by measuring the rate of
      mediator regeneration by the cell. Depending on the properties of the mediator
      species (e.g., formal potential, ionic charge, and hydrophobicity), different
      steps can limit the rate of the mediator regeneration reaction. This paper
      describes the evaluation of several factors that determine the rates of different
      steps of the process. These include intracellular concentration of redox centers,
      mixed redox potential inside the cell, and the rate of membrane permeation by
      mediator species. The kinetic analysis has been carried out to clarify the
      origins of different rates of the overall charge-transfer reaction in different
      cell types and with different redox mediators. The results can be used to
      facilitate differentiation between different types of cells, for example, normal
      and metastatic breast cells, on the basis of differences in redox responses.

PMID- 12510758
TI  - Electrochemical and Raman studies of the biointeraction between Escherichia coli
      and mannose in polydiacetylene derivative supported on the self-assembled
      monolayers of octadecanethiol on a gold electrode.
AB  - Here, we describe a new method to study the biointeraction between Escherichia
      coli and mannose by using supramolecular assemblies composed of polydiacetylene
      supported on the self-assembled monolayer of octadecanethiol on a gold electrode.
      These prepared bilayer materials simply are an excellent protosystem to study a
      range of important sensor-related issues. The experimental results from UV-vis
      spectroscopy, resonance Raman spectroscopy, and electrochemistry confirm that the
      specific interactions between E. coli and mannose can cause conformational
      changes of the polydiacetylene backbone rather than simple nonspecific
      adsorption. Moreover, the direct electrochemical detection by polydiacetylene
      supramolecular assemblies not only opens a new path for the use of these
      membranes in the area of biosensor development but also offers new possibilities
      for diagnostic applications and screening for binding ligands.

PMID- 12510759
TI  - Fabrication of submicrometer-sized gold electrodes of controlled geometry for
      scanning electrochemical-atomic force microscopy.
AB  - A method for fabricating submicrometer-sized gold electrodes of conical or
      spherical geometry is described. By generating an electric arc between an etched
      gold microwire and a tungsten counter electrode, the very end of the gold
      microwire can be melted and given an overall spherical or conical shape a few
      hundred nanometers in size. The whole wire is subsequently insulated via the
      cathodic deposition of electrophoretic paint. By applying a high-voltage pulse to
      the microwire, the film covering its very end can then be selectively removed,
      thus exposing a submicrometer-sized electrode surface of predefined geometry. The
      selective exposure of the preformed end of the microwire is demonstrated by
      cyclic voltammetry, scanning electron microscopy, and metal electrodeposition
      experiments. The electrophoretic paint coating provides a low-capacitance, robust
      insulating film allowing exploration of a very wide potential window in aqueous
      solution. The submicrometer-sized electrodes can easily be turned into probes
      suitable for combined scanning electrochemical-atomic force microscopy by bending
      and flattening the gold microwire so that the tip is borne by a flexible enough
      arm. The good agreement between theoretical and experimental scanning
      electrochemical microscopy approach curves thus obtained confirms that only the
      very end of the tip, of predefined geometry, is exposed to the solution.

PMID- 12510760
TI  - Electrochemical flow injection analysis study of ion partitioning at high surface
      area carbon fiber electrodes.
AB  - Charge-selective electrochemistry was previously shown to occur at high surface
      area carbon fibers that were produced by fracturing the outer periphery with
      anodic current or positive potential. The cyclic voltammetric behavior of
      electroactive species observed at these fibers exhibited a distinct pH dependence
      related to the protonation/deprotonation of oxygen-containing functional groups
      at the surface of the carbon fiber. In this paper, electrochemical flow injection
      analysis (EC-FIA) is used to probe ion partitioning in to and out of the interior
      microstructure of the treated carbon fiber, for both electroactive and
      electroinactive species. It was found that the extent of partitioning was the
      result of both ion charge and hydrated ionic radius, in addition to the level of
      fracture. It was further observed that the direction of movement for an injected
      ionic species could be controlled relative to the ion concentration, the pH of
      the carrier solution, or both. EC-FIA allowed the simultaneous observation of
      current due to ion movement and that due to electron transfer to a redox-active
      species. The results presented are consistent with a model in which fixed
      negatively charged sites in the interior of fractured fibers govern ion
      partitioning with positively charged ions in the carrier solution, with
      counterions located in the interior "free" volume.

PMID- 12510761
TI  - Indirect measurement of nitric oxide production by monitoring nitrate and nitrite
      using microchip electrophoresis with electrochemical detection.
AB  - An indirect method for monitoring nitric oxide (NO) by determining nitrate and
      nitrite using microchip capillary electrophoresis (CE) with electrochemical (EC)
      detection has been developed. This method combines determination of nitrite by
      direct amperometric detection following a microchip-based CE separation and
      conversion of nitrate to nitrite by chemical reduction using Cu-coated Cd
      granules. The amount of nitrate is quantified by calculating the difference in
      the amount of nitrite in the sample before and after the reduction of nitrate.
      Optimization of the separation, injection, detection, and reduction reaction
      conditions, as well as studies involving integration of the reduction reaction
      onto the microchip, are described. It was found that nitrite can be separated and
      detected in approximately 45 s by microchip CEEC. The reduction reaction was
      successfully integrated on-chip and carried out in approximately 1 min following
      activation of the Cd granules. The usefulness of this device was demonstrated by
      monitoring the amount of nitrate and nitrite produced from 3
      morpholinosydnonimine, a NO-releasing compound.

PMID- 12510762
TI  - High-voltage capacitively coupled contactless conductivity detection for
      microchip capillary electrophoresis.
AB  - Contactless conductivity detection was carried out on a planar electrophoresis
      device by capacitive coupling using an ac excitation voltage of 500 V(p-p) and a
      frequency of 100 kHz. It was possible to carry out detection in this way through
      a cover plate of 1 mm thickness. Better sensitivity is obtained, however, by
      placing the electrodes into troughs that allow tighter coupling to the separation
      channel. The 3 x S/N detection limits are 0.49, 0.41, and 0.35 microM for the
      small inorganic ions K+, Na+, and Mg2+. The detection of heavy metals is
      demonstrated with the example of Mn2+, Zn2+, and Cr3+ with detection limits of
      2.1, 2.8, and 6.8 microM, respectively. The universal nature of the method is
      further illustrated by the detection of citric and lactic acids, which are of
      interest in food and beverage analysis, and detection of three antiinflammatory
      nonsteroid drugs, 4-acetamidophenol, ibuprofen, and salicylic acid, as examples
      of species of pharmaceutical interest.

PMID- 12510763
TI  - Thin films of block copolymer blends for enhanced performance of acoustic wave
      based chemical sensors.
AB  - The performance of quartz crystal oscillator-based volatile organic compound
      (VOC) sensors has been enhanced by using coatings made from poly(styrene-block
      ethylene-co-butylene-block-styrene) block copolymers blended with resins and
      homopolymers. Enhanced performance is characterized by a wider operational
      temperature range (-10 to +50 degrees C) over which the sensors displayed,
      concurrently, an analyte sensitivity of >0.2 Hz/ppm toluene, minimal energy loss
      (resistance <120 ohms), and response times of <20 min (time required to reach 90%
      of full response). Atomic force microscopy images are consistent with a process
      in which the additive associates with the polystyrene portions of the microphase
      separated block copolymer. This association reinforces the rigidity of the
      polystyrene network while allowing the rapid uptake of VOCs by the softer
      polyethylene/butylene phase.

PMID- 12510764
TI  - Microfluidic actuation using electrochemically generated bubbles.
AB  - Bubble-based actuation in microfluidic applications is attractive owing to
      elementary microfabrication requirements. In the present study, the mechanical
      and chemical characteristics of electrochemically generated bubble valves were
      studied. By generating electrochemical bubbles as valves directly inside the
      channel, valves could be closed and opened in milliseconds. Whereas bubble
      inflation (or valve closing) rate increases with applied voltage, small
      microfluidic dimensions accelerate bubble deflation rates. It is found that
      bubbles need not collapse fully to restore full flow, and the channel opens when
      its hydraulic resistance equals that between the bubble and the wall--a process
      requiring only milliseconds. Since only picomoles of salt are needed to generate
      bubbles, pH gradients that are invariably associated with electrochemical
      reactions were readily suppressed by using a small amount of buffer, as
      visualized by a pH-sensitive fluorescent dye. A range of common laboratory
      reagents and electrolytes in varying concentrations, including weak to strong
      acids and bases, as well as nonaqueous/aqueous mixtures were successfully tested.
      Using such bubble valves, an eight-way multiplexer was fabricated and tested.

PMID- 12510765
TI  - Xanthamide fluorescent dyes.
AB  - Two derivatives of fluorescein, termed "xanthamides," were prepared from
      fluorescein, an inexpensive dye. Relative to fluorescein, which contains a 6
      phenolic OH and a 2'-carboxyl, the first derivative (5) contains a carboxymethyl
      ether at the 6-position and a secondary amide of dimethylamine at the 2'
      position. The second derivative (8) contains a corresponding 6-methyl ether and a
      secondary amide of isonipecotic acid at the 2'-position. Thus, both derivatives
      contain a single carboxyl group, making them monofunctional. Especially 8 is much
      more photostable (about 10 times) than either fluorescein or BODIPY FL dye when
      exposed to ordinary light (tungsten light bulb). When tested for relative
      response in a capillary electrophoresis instrument fitted with an argon ion laser
      detector (488 nm) and a broad band emission filter, 8 was found to be 4-fold less
      bright than fluorescein. Both xanthamides, consistent with prior literature on 6
      O-alkylated fluorescein, exhibit relatively pH-independent fluorescence (pH 4-10
      was tested here). Because they possess two absorbance maximums, the xanthamides
      can be excited over a broader wavelength range than fluorescein or BODIPY. These
      collective properties of the xanthamides will make them advantageous over
      fluorescein and BODIPY dyes for some applications.

PMID- 12510766
TI  - Fourier transform infrared analysis of gas composition in low-volume light bulbs.
AB  - Fourier transform infrared spectroscopy has been used for in situ analysis of
      HBr, CH3Br, and CO within light bulbs at different stages of burning time. The
      interference fringes originated in the quartz walls of the bulbs have been
      eliminated by different methods. The NIPALS procedure yielded higher S/N ratio
      than the fringe-elimination method applied. The CO and HBr showed time-dependent
      concentration changes during the burning period. The maximum CO concentration
      (approximately 6 ppm) was detected after 30-50 s of burning time, and then it
      practically burned out after 5 h. The HBr concentration increased in the first 3
      min of burning, and then its concentration stabilized at a 10-15 ppm level. After
      5 s of illumination, the CH3Br concentration became undetectable.

PMID- 12510767
TI  - Direct isolation of purines and pyrimidines from nucleic acids using sublimation.
AB  - A sublimation technique was developed to isolate purines and pyrimidines directly
      from lambda-deoxyribonucleic acid (lambda-DNA) and Escherichia coli cells. The
      sublimation of adenine, cytosine, guanine, and thymine from lambda-DNA was tested
      under reduced pressure (approximately 0.5 Torr) at temperatures of >150 degrees
      C. With the exception of guanine, approximately 60-75% of each base was sublimed
      directly from the lambda-DNA and recovered on a coldfinger of the sublimation
      apparatus after heating to 450 degrees C. Several nucleobases including adenine,
      cytosine, thymine, and uracil were also recovered from E. coli bacteria after
      heating the cells to the same temperature, although some thermal decomposition of
      the bases also occurred. These results demonstrate the feasibility of using
      sublimation to isolate purines and pyrimidines from native E. coli DNA and RNA
      without any chemical treatment of the cells.

PMID- 12510768
TI  - Gains in sensitivity with a device that mixes microarray hybridization solution
      in a 25-microm-thick chamber.
AB  - A microarray hybridization system that allows mixing in volumes comparable to
      those used by glass coverslips is presented. This system is composed of a
      disposable flexible lid that binds to 1 in. x 3 in. glass slides via an adhesive
      gasket, forming a uniform 25-microm-thick hybridization chamber. This chamber
      rests on a base unit for temperature control. The lid contains two air-driven
      bladders that continuously mix the hybridization fluid. Mixing enhances
      sensitivity from a typical microarray experiment 2-3-fold. Mixing is particularly
      effective at high spotted probe and low labeled target concentrations and
      overcoming local target depletion that occurs when homologous probes are spotted
      in close proximity. Mixing appears to be compatible with most hybridization
      conditions; however, mix versus no-mix control experiments should be performed.
      Also covered are a number of microfluidic issues related to manufacturing,
      filling, mixing, and packaging.

PMID- 12510769
TI  - 4-Nitro-7-piperazino-2,1,3-benzoxadiazole as a reagent for monitoring of airborne
      isocyanates by liquid chromatography.
AB  - 4-Nitro-7-piperazino-2,1,3-benzoxadiazole (NBDPZ) is presented as a new reagent
      for the determination of mono- and diisocyanates in air samples. NBDPZ readily
      reacts with the airborne analytes, thus yielding the corresponding urea
      derivatives, which are subsequently separated by means of reversed-phase liquid
      chromatography. On a phenyl-modified stationary phase, excellent baseline
      separation for numerous mono- and diisocyanate derivatives is obtained. Both
      diode array and fluorescence detection are performed with limits of detection of
      11-35 and 5-9 nmol/L for the individual derivatives, respectively. In contrast to
      established derivatizing agents for the analysis of isocyanates, NBDPZ provides
      for increased selectivity due to the favorable detection wavelengths in the
      visible range (UV/visible, absorption maximums approximately 480 nm;
      fluorescence, excitation maximums approximately 470 nm, emission maximums
      approximately 535 nm). In addition, the high molar absorptivities of the reagent
      and the derivatives provide excellent sensitivity that is superior to most
      literature-known methods. Finally, air sampling methods comprising both the use
      of impingers and test tubes are developed and successfully applied to the
      determination of isocyanates in gaseous samples. Excellent recovery reaching
      values of >90% is observed for each of the two techniques investigated.

PMID- 12510770
TI  - Feasibility of formation of hot ions in electrospray.
AB  - Internal energy changes during the electrospray process have been studied. Our
      results suggest that, contrary to conventional wisdom, ions that are quite hot
      are formed in electrospray, even without acceleration in the cone-skimmer region.
      The main role of the curtain gas seems to be not to break up existing clusters
      but, rather, to cool down the nascent ions and to prevent cluster formation by
      shielding them from solvent vapors.

PMID- 12510771
TI  - Comment on "Determination of total sulfur at microgram-per-gram levels in
      geological materials by oxidation of sulfur into sulfate with in situ generation
      of bromine using isotope dilution high resolution ICP MS".

PMID- 12510772
TI  - Identification of an alternatively spliced RNA for the Ras suppressor RSU-1 in
      human gliomas.
AB  - Previous studies demonstrated that the Ras suppressor, RSU-1, localizes to human
      chromosome 10p13, a region frequently deleted in high grade gliomas, and that RSU
      1 expression inhibited the tumorigenesis of a glioblastoma cell line. We have now
      examined RNA from human glial tumors for RSU-1 expression by RT-PCR using primers
      for the 5' and 3' ends of the RSU-1 open reading frame. Analysis of the amplified
      RSU-1 cDNA demonstrated that in addition to the entire 858 bp RSU-1 open reading
      frame, a shorter 725 bp RSU-1 fragment was amplified as well. Sequencing of this
      product revealed that it encoded a RSU-1 cDNA product which was missing a single
      133 bp internal exon. This exon-deleted product was found in 30% of the high
      grade gliomas studied and 2/3 oligodendrogliomas, but not in other CNS tumors,
      bladder or colon tumors or normal tissue. The exon-deleted RSU-1 product was
      infrequently detected in RNA from human tumor cell lines. Expression of an HA
      tagged form of the deleted RSU-1 protein in transfected Cos 1 cells revealed that
      the protein was unstable, with a half life of less than 1 h, in contrast to the
      full length HA-tagged Rsu-1 protein which was stable for more than 4 h. These
      results suggest that the alternative splicing of the RSU-1 RNA to produce the
      exon-deleted form constitutes a mechanism for reduction or loss of functional Rsu
      1. Because the expression of Rsu-1 can inhibit malignant growth of glioblastoma
      cells, the depletion of Rsu-1, via the production of the alternatively spliced
      form of RSU-1, may inhibit growth regulation in tumors.

PMID- 12510773
TI  - cDNA array analysis of SPARC-modulated changes in glioma gene expression.
AB  - We have demonstrated that secreted protein acidic and rich in cysteine (SPARC) is
      highly expressed in human gliomas and it promotes glioma invasion and delays
      tumor growth in vitro and in vivo. cDNA array analyses were performed to
      determine whether SPARC, which interacts at the cell surface, has an impact on
      intracellular signaling and downstream gene expression changes, which might
      account for some of its effects on invasion and growth. Using a doxycycline (dox)
      controlled gene expression system, two cDNA array analyses were performed using a
      parental U87T2 clone (-SPARC) transfected with the dox-controlled transactivator
      and a U87T2 parental-derived SPARC-transfected clone, A2b2 (+SPARC). Array
      analysis performed between the parental and the SPARC-transfected clone (-dox)
      identified 13 upregulated genes and 14 downregulated genes. With the exception of
      PAI-1 and MMP2, the identified genes are novel with respect to SPARC's mechanism
      of action. Array analysis performed using the SPARC-transfected clone ( +/- dox)
      identified 2 types of gene regulation; one reversible upon SPARC suppression, the
      other irreversible. Two of the SPARC-induced genes, BIGH3 (irreversible by dox)
      and PAI-1 (reversible by dox) were further studied in additional SPARC
      transfected clones, human astrocytoma tissues, and human glioma cell lines by RT
      PCR and Northern blot analyses. The results indicate that: (1) the array results
      were validated, (2) the dox regulation was validated, and (3) the differential
      expression identified by the array analyses was present between normal brain and
      in human astrocytoma tissues and cell lines. Therefore, we conclude that these
      cDNA array analyses provide candidate genes involved in SPARC-mediated effects on
      glioma cell cycle progression, signaling, and migration, and that SPARC may
      induce reversible and irreversible gene expression changes. Further investigation
      of these candidates may shed insights into SPARC's role in glioma cell
      proliferation and invasion, and potential use as a therapeutic target.

PMID- 12510774
TI  - Results of three-dimensional stereotactically-guided radiotherapy in recurrent
      medulloblastoma.
AB  - PURPOSE: To evaluate survival rates and side effects after stereotactically
      guided radiotherapy (SRT) in patients with recurrent medulloblastoma of the
      brain. METHODS AND MATERIALS: Between 1992 and 2000, 20 patients with 29
      radiological manifestations were treated with fractionated SRT (n = 21) or
      radiosurgery (n = 8). Median age was 16 years with 6 patients < or = 14 years.
      All patients had prior cranio-spinal radiotherapy plus boost to the posterior
      fossa with a total dose of 54 Gy. Time to recurrence was 33 months mean. Eighteen
      of the 29 lesions were located within the boost volume. Chemotherapy was given
      according to current international study protocols (HIT) in all patients. Mean
      total dose for re-irradiation was 24 Gy for fractionated stereotactically-guided
      radiotherapy, and 15 Gy for radiosurgery. Mean follow-up was 88.5 months.
      RESULTS: Overall local control was 89.7%. Thirteen recurrences showed partial or
      complete response in CT/MR-imaging, 13 showed stable disease. Local tumor
      progression was seen 5 months mean after radiotherapy in three cases. A
      multifocal intracranial progression was seen in 9 patients, 5 patients developed
      additional spinal metastases. Thirteen patients died with disseminated cranio
      spinal progression, after 72.6 months median. No late toxicity > CTC II(o)
      especially no brain radionecrosis was seen after radiotherapy. CONCLUSION: SRT is
      effective and safe in the treatment of recurrent medulloblastoma to improve local
      control without evident side effects. The main problem remains the control of
      subclinical cranio-spinal dissemination.

PMID- 12510775
TI  - Correlation of clinical and biological parameters with peritumoral edema in
      meningioma.
AB  - Peritumoral edema (PTE) in meningioma occurs variably and can adversely affect
      the clinical course. Moreover, the etiology of PTE in meningioma is not well
      documented. To examine possible correlations with PTE, the authors investigated
      the clinical parameters and the expressions of vascular endothelial growth factor
      (VEGF), matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) in 20
      meningiomas. The estimation of tumor volume (V(T)) and edema volume (V(E)) was
      done using Osiris software with magnetic resonance images and the edema index
      (EI) was calculated. The expression of VEGF, MMP, and TIMP were estimated in all
      20 meningiomas by immunohistochemical staining, Western blotting, zymography, and
      laser densitometry. Tumor location was closely related with PTE. Meningiomas of
      the frontal lobe or the frontotemporal base had large PTEs, whereas those of the
      occipitoparietal lobe, posterior fossa or petroclivus were small. The level of
      VEGF expression bore correlation with the extent of PTE but not with histologic
      malignancy. MMP-2 and -9 were detected in 100% of meningiomas by zymography. The
      levels of MMP-9 were significantly elevated in moderate to severe edema (EI >
      1.0) group (p < 0.05) whereas those of MMP-2 were elevated in minimal to mild
      edema (EI < 1.0) group. TIMP-1 and -2 were detected in 19 (95%) and 12 (60%) of
      meningiomas respectively and their presence had no significant correlations
      statistically with PTE between two groups (p = 0.190 and 0.089, respectively).
      Meningiomas with severe PTE expressed high levels of VEGF and MMP-9 and low
      levels of MMP-2. The expressions of MMP-2, -9, and TIMPs as well as VEGF in
      meningioma suggests that they are strongly related with the presence of PTE in
      meiningiomas, and that they might play the important role in the formation of PTE
      in meningiomas.

PMID- 12510776
TI  - Medulloblastoma in adults: a series from Brazil.
AB  - We retrospectively reviewed 15 adult patients (11 males, median age 34 years;
      range 23-48) who had been treated and followed in our Institution since 1991 from
      the time of diagnosis until death or last follow-up in December 2001. Headache
      was the most frequent symptom (93%). The tumor was hemispheric in 11 patients.
      Complete resection was achieved in eight. CSF in 12 patients and craniospinal MRI
      in 6 did not show metastatic disease. Two patients refused adjuvant treatment and
      died with progressive disease. Thirteen patients received adjuvant craniospinal
      radiotherapy and 11 systemic chemotherapy. After initial treatment only 2 of the
      13 patients relapsed in the posterior fossa. Recurrence was probably related to
      sub-optimal radiotherapy planning: inadequate low dose in the posterior fossa
      (37.5 Gy) and long delay in initiating treatment. Two of the 13 patients that
      received adjuvant treatment died: one from meningitis, and one from recurrent
      disease. Eleven patients remained alive, and disease-free with Karnofsky
      performance status ranging 80-100. The median overall survival was not reached
      after a median follow-up of 5.6 years (range 0.7-10.8 years). Estimated 1-, 5-
      and 10-year overall survival rates were 86.7%, 72.7%, and 72.7%, respectively.
      Adult medulloblastoma was predominant in males and the majority of patients had
      hemispheric tumors. Long-term survival was not uncommon. Although chemotherapy
      may be useful and well tolerated, radiotherapy remains the mainstay adjuvant
      treatment as suggested by our two recurrences associated with a delay or
      inadequate dose.

PMID- 12510777
TI  - Intracranial ependymomas in adult patients: analyses of prognostic factors.
AB  - OBJECTIVE: The goal of our study is to identify significant prognostic factors
      for a series of intracranial ependymomas in an adult population. Age, location,
      histology, preoperative clinical status, extent of resection and radiotherapy
      were examined. METHODS: Our series includes 34 patients. Ten tumors were located
      in the brain parenchyma, 5 in the lateral ventricle, 8 in the third and 11 in the
      fourth ventricle. Seventeen ependymomas were grades 2 and 17 were anaplastic.
      Surgical resection was gross-total in 27 patients and partial in 7. RESULTS: At a
      mean follow-up of 9 years (+/- 1 year) 16 patients died and, among the 18
      survivors 14 are in complete remission and 4 present a local recurrence. The 5-
      and 10-year overall survival rates were respectively 62% and 43%. The 5- and 10
      year progression-free survivals were 47% and 43%. Univariate analysis revealed
      that location in the brain parenchyma and anaplasia are the only statistically
      significant predictors of poor outcome. CONCLUSION: We can make out three groups
      of patients from our series: the first encompasses patients operated on for an
      intraparenchymal tumor, in all our cases an anaplastic ependymoma, with a 5-year
      rate of tumor-related deaths of 100%. The second group includes fourth ventricle
      ependymomas, which are mostly grade 2 tumors. They display a 10-year survival
      rate of 90%. Last group entails lateral and third ventricle ependymomas, of both
      low and high grade, with a 10-year survival rate of 60% for lateral ventricle and
      35% for third ventricle tumors.

PMID- 12510778
TI  - Prolonged infusional topotecan and accelerated hyperfractionated 3d-conformal
      radiation in patients with newly diagnosed glioblastoma--a phase I study.
AB  - PURPOSE: Topotecan has demonstrated exceptional central nervous system
      penetration as well as radiosensitizing properties in glioblastoma xenografts
      [Chastagner et al., Int J Radiat Oncol Biol Phy 50: 777-782, 2001]. This phase I
      trial was performed to determine the maximum tolerated dose and the recommended
      dose of topotecan continuous infusion administered together with concomitant
      radiotherapy in patients with glioblastoma. PATIENTS AND METHODS: A total of 20
      patients were treated in this trial. Twenty one day topotecan continuous infusion
      was escalated from 0.3 mg/m2/d in increments of 0.1 mg/m2/d and cohorts of 3-6
      patients until maximum tolerated dose was reached; Three-dimensional (3d)
      conformal radiotherapy was applied concurrently twice daily with a fraction size
      of 1.75 Gy up to 57.75 Gy total dose. Three additional cycles of maintenance
      topotecan chemotherapy were scheduled. RESULTS: Fifty-three courses were
      performed in 5 dose levels (0.3 mg/m2/d: 12 cycles, 0.4 mg/m2/d: 6 cycles, 0.5
      mg/m2/d: 10 cycles, 0.6 mg/m2/d: 6 cycles, 0.7 mg/m2/d: 19 cycles). Maximum
      tolerated dose was reached at dose level 5 (0.7 mg/m2/d), because 3/7 patients
      suffered from dose limiting toxicity. These were febrile sinusitis, bacterial
      sepsis and grade 4 thrombocytopenia. Neutropenia of grade 4 was encountered in 2
      cycles (0.5 and 0.7 mg/m2/d). Response data were available in 17 patients, 3 of
      which (18%) achieved partial remission, 12 (71%) stable disease throughout the
      observation period and 2 (11%) progressive disease. CONCLUSION: The recommended
      dose for further trials will be 0.6 mg/m2/d topotecan administered as 21 days
      continuous infusion in combination with accelerated 3d conformal radiation.

PMID- 12510779
TI  - Rock climbers' self-perceptions of first aid, safety, and rescue skills.
AB  - OBJECTIVE: Rock climbing is a challenging and demanding sport that requires
      specialized equipment and training. One significant area of training involves
      being familiar with first aid and rescue skills. This study reports climbers'
      self-perceptions of their first aid, safety, and rescue skill competencies.
      Actual technical skills were not measured. METHODS: Data were collected through a
      World Wide Web (WWW)-based questionnaire administered over a 15-month period. The
      questionnaire requested information on respondents' climbing history, first aid
      training, personal safety practices, and partner and self-rescue skills. RESULTS:
      Two hundred forty-one climbers completed the Web-based survey. Findings showed
      that the majority of climbers reported receiving some form of first aid training,
      were attentive to personal safety practices, and perceived themselves to be
      confident in partner and self-rescue techniques. CONCLUSIONS: On the basis of the
      results obtained in this study, it appears that training and specialized skills
      are considered by rock climbers to be important components of managing risk.

PMID- 12510780
TI  - Skiing, snowboarding, and sledding injuries in a northwestern state.
AB  - OBJECTIVE: Winter sports continue to be a popular form of recreation, but few
      studies have focused on serious injuries. The objectives of this study were to
      evaluate the major morbidity associated with downhill skiing, snowboarding, and
      sledding and to determine the incidence of serious injuries sustained while
      downhill skiing and snowboarding. METHODS: State trauma registry data from the
      1992-93 through 1998-99 ski seasons on all snow sports participants transported
      to tertiary trauma hospitals in Oregon were analyzed. RESULTS: Of 132 patients,
      80% were male and 20% were female, with a mean age of 30.4 +/- 15.6 for skiers,
      24.1 +/- 10.5 for snowboarders, and 18.8 +/- 11.9 for sledders. The mean Injury
      Severity Score was 12.3 +/- 7.6 for skiers, 10.3 +/- 7.4 for snowboarders, and
      12.8 +/- 8.5 for sledders. Head injuries accounted for 55% of sledding injuries
      and 39% of all injuries. Skiers and snowboarders were less likely to have head
      injuries than sledders (odds ratio [OR] = 0.45; 95% CI, 0.21 to 0.98). A higher
      proportion of injuries sustained by snowboarders were due to falls from heights
      (29%) compared with injuries sustained by skiers or sledders (OR = 4.8; 95% CI,
      1.6 to 13.7). Sledders were more likely to be injured during collisions than were
      skiers or snowboarders (OR = 16.7; 95% CI, 5.8 to 47.6). The incidence of serious
      skiing and snowboarding injuries was 6.4 injuries per million visits. There were
      4 deaths (3%), 1 each from snowboarding and skiing (head injuries) and 2 from
      sledding (1 from head and 1 from head and thoracic injuries). CONCLUSIONS:
      Serious snow sports injuries are rare but potentially debilitating. Head injuries
      account for the majority of deaths and functional impairment.

PMID- 12510781
TI  - An outbreak of blastomycosis on a United States Indian reservation.

PMID- 12510782
TI  - Evaluation of the System O2 Inc portable nonpressurized oxygen delivery system.
AB  - OBJECTIVE: To evaluate the performance of the System O2 portable non-pressurized
      delivery system (SysO2). This device produces oxygen through chemical reaction
      and might have utility for emergency/field use. METHODS: Performance was
      evaluated with 10 unmanned trials conducted under standard laboratory conditions.
      Measures included oxygen flow (mean and peak), total oxygen yield, and system
      weight-indexed yield. RESULTS: Oxygen flow peaked at 5.74 +/- 0.28 L x min(-1)
      (mean +/- SD) at 16.9 +/- 1.5 minutes before rapidly falling to zero. Mean flow
      was 2.98 +/- 1.52 L x min(-1) with a total yield of 62.9 +/- 6.6 L. Mean oxygen
      fraction was 0.96 +/- 0.15. The weight per unit of oxygen is substantially higher
      than for commercially available pressurized cylinders; e.g., 47.7 vs. 10.2 g x L(
      1) for the small 246 L M9 cylinder. CONCLUSIONS: Given the limited flow rate and
      supply duration, we believe the SysO2 system does not offer significant advantage
      over the available pressurized oxygen systems as a source for emergency oxygen.

PMID- 12510783
TI  - Tetanus after white-lipped green pit viper (Trimeresurus albolabris) bite.

PMID- 12510784
TI  - Clinical images. Cold stress.

PMID- 12510785
TI  - A model for wilderness medicine education in a family practice residency.

PMID- 12510786
TI  - Black widow spider envenomation in a 36-year-old man.

PMID- 12510787
TI  - A historical reference for snowboarding injuries.

PMID- 12510788
TI  - The metabolic syndrome, type 2 diabetes, and cardiovascular disease:
      understanding the role of insulin resistance.
AB  - The most common and clinically important complication in adults with diabetes is
      cardiovascular disease (CVD), which includes coronary heart disease, peripheral
      vascular disease, and stroke. Both type 2 diabetes and the insulin resistance
      syndrome are associated with a marked increase in the risk for CVD. The metabolic
      syndrome and the closely related insulin resistance syndrome have recently been
      recognized as important disorders, each being associated with an increase in CVD
      risk even in the absence of glucose intolerance. Given the significant public
      health burden of CVD, risk reduction has emerged as a significant clinical
      challenge for most practitioners. Diabetes and the insulin resistance syndrome
      are closely related disorders, with insulin resistance being more than a key
      pathogenic defect in type 2 diabetes. Even in the absence of glucose intolerance,
      these 2 disorders are both associated with a number of distinct pathologic
      findings, including hypertension, atherogenic dyslipidemia, a prothrombotic
      environment, and significant vascular and hemodynamic abnormalities that result
      from endothelial cell dysfunction. Insulin resistance is now recognized to be
      closely associated with the development of each of these risk factors. This
      article uses a case-based approach to discuss the unique features of insulin
      resistance and type 2 diabetes considered to be key contributors to CVD risk. A
      systematic approach to both evaluation and management is proposed, with priority
      given to therapies of demonstrated clinical benefit. Because of its critical and
      central role in the development of many CVD risk factors, targeted treatment of
      insulin resistance will also be discussed as such therapy may prove to be a
      critical component of care in years to come.

PMID- 12510789
TI  - Insight into some of the signaling pathways triggered by a lipid immunomodulator.
AB  - The use of non specific immunomodulatory agents takes an important place in the
      aspecific host response to invading microorganisms. In this context,
      antimicrobial properties of royal jelly have been ascribed to organic acids
      (mainly 10 hydroxy-2-decenoic acid or 10-HDA) and proteins. We synthesized a
      derivative of 10-HDA, the 1-(2-methoxyethoxymethyl)2,3-(10-hydroxy2-decenoyl)(E)
      glycerol referred as diHDA-glycerol which was previously found to protect mice
      against virulent Salmonella typhimurium challenge through more adequate immune
      regulations. This study was conducted to further investigate some of the
      signaling pathways followed by diHDA-glycerol in cell transduction. Members of NF
      kappaB transcription factors are key regulators of many cytokines acting on
      immunity and they control genes involved in responses to numerous signals such as
      bacterial products. Therefore, we investigated some parameters acting on NF
      kappaB translocation in U937 cells after diHDA-glycerol treatment. Due to the
      chemical structure of the molecule we also investigated the sphingomyelinase
      pathway. Our results showed that diHDA-glycerol induced a rapid NF-kappaB
      translocation as a consequence of IkappaB-alpha proteolysis. An intracellular
      production of reactive oxygen species (ROS) may also account for NF-kappaB
      activation, without de novo protein synthesis. DiHDA-glycerol induced a strong
      activation of neutral sphingomyelinase, suggesting an important role of
      sphingolipids in the regulatory responses induced by diHDA-glycerol.

PMID- 12510790
TI  - Comparative study and effects of macrophage colony-stimulating factor (M-CSF)
      administration on NK1.1+ cells in mouse spleen and bone marrow.
AB  - We conducted a comparative study of NK1.1+ cells in spleen and bone marrow and
      the effects of administration of M-CSF on them. Administration of M-CSF to mice
      increased the number of NK1.1+ cells in spleen but not in bone marrow. The NK1.1+
      cells in spleen (Spl-NK1.1) and bone marrow (BM-NK1.1) were purified by magnetic
      cell sorter. Their cell surface markers and functions were then examined. The
      percentage of Mac-1 antigen-positive cells (and F4/80 antigen-positive cells) was
      higher among BM-NK1.1 than Spl-NK1.1. Moreover, the administration of M-CSF
      increased the number of Mac-1 and F4/80 antigen-positive cells in both Spl-Nk1.1
      and BM-NK1.1. The functions (cytolytic activity and IFN-gamma production) of Spl
      NK1.1 and BM-NK1.1 were the same and were enhanced by the administration of M
      CSF. But Spl-NK1.1 produced more IFN-gamma than BM-NK1.1 when M-CSF was
      administered. BM-NK1.1 showed a greater proliferative response to IL-2 than Spl
      NK1.1. Administration of M-CSF augmented this response. BM-NK1.1 proliferated in
      response to IL-4 and IL-15, but Spl-NK1.1 responded only slightly. However,
      administration of M-CSF stimulated Spl-NK1.1 to respond to these cytokines. Both
      Spl-NK1.1 and BM-NK1.1 showed only a weak response to M-CSF in vitro. But the
      expression of c-fms antigen (M-CSFR) increased after the M-CSF injections in
      vivo. These results suggested that there are phenotypical and functional
      differences between Spl-NK1.1 and BM-NK1.1. The administration of M-CSF led to an
      accumulation of NK1.1+ cells which were mobilized from bone marrow in spleen.

PMID- 12510791
TI  - Helicobacter pylori organisms induce expression of activation and apoptotic
      surface markers on human lymphocytes and AGS cells: a cytofluorimetric
      evaluation.
AB  - Human peripheral blood mononuclear cells (PBMCs) were treated with Helicobacter
      pylori (Hp) organisms alone or with Hp-stimulated AGS cells (a gastric
      adenocarcinoma cell line). Hp organisms were able per se to increase the
      percentage of CD8 +/- CD95 +/- cells, while number of CD25+ cells and HLA-DR
      molecule expression increased following pretreatment with Hp-stimulated AGS
      cells. A comparison was made with a test system in which PBMCs were stimulated
      with Escherichia coli (Ec) organisms and colo-cells (a colon carcinoma cell
      line). In this case, CD95+ cells and CD25+ cells increased when the combination
      Ec organisms/colo-cells was present in the culture. On the other hand, Hp
      bacteria in combination with colo-cells were not able to induce activation and/or
      apoptotic surface markers on PBMCs, while Ec-stimulated AGS cells increased the
      expression of CD95 on PBMC. Finally, the direct interaction of AGS cells with Hp
      was able to induce higher expression of CD95 on gastric epithelial cells than Hp
      stimulated PBMCs. Taken together, these data support the interplay between
      bacteria and epithelial cells in the course of Hp-mediated gastropathy.

PMID- 12510792
TI  - Inhibitory effect of mast cell-mediated acute and chronic allergic reactions by
      Dodutang.
AB  - Dodutang has been used for treatment of various allergic inflammation diseases in
      Korea. However, it is still unclear how Dodutang prevents these diseases in
      experimental animal models. Mast cells play an important roles in allergic and
      other inflammatory reactions by producing a spectrum of powerful mediators
      including preformed and de novo synthesized cytokines. In this study, we
      investigated the effect of Dodutang on mast cell-mediated allergic and
      inflammatory reactions. Dodutang (0.001-5 g/L) significantly inhibited the
      histamine release from rat peritoneal mast cells activated by compound 48/80.
      Dodutang (0.001-5 g/kg) dose-dependantly inhibited the passive cutaneous
      anaphylaxis reaction activated by anti-dinitrophenyl (DNP) IgE in a rat model,
      especially, by 78.96% at the concentration of 5 g/kg. In addition, Dodutang
      potently inhibited the secretion of tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta in phorbol 12-myristate 13-acetate plus calcium ionophore
      A23187-stimulated human mast cells. However, IL-6 secretion was enhanced at the
      same conditions. Dodutang also inhibited the main inflammatory cytokine TNF-alpha
      protein expression in human mast cells. These results provide evidences that
      Dodutang may be beneficial in the treatment of acute and chronic allergic
      diseases.

PMID- 12510793
TI  - Radioprotective efficacy and acute toxicity of 5-androstenediol after
      subcutaneous or oral administration in mice.
AB  - We previously showed that one subcutaneous (sc) injection of 5-androstene
      3beta,17beta-diol (AED) stimulated the innate immune system in mice and prevented
      mortality due to hemopoietic suppression after whole-body ionizing irradiation
      with gamma rays. In the present study, we tested whether there was any
      significant toxicity in mice that might hinder development of this steroid for
      human use. There were no indications of toxicity in chemical analyses of serum
      after sc doses as high as 4000 mg/kg. At this dose, 2 of 54 mice died when given
      AED alone. When 4800 mg/kg was given orally, no deaths resulted. The only adverse
      findings attributed to AED administration were 1) a moderate elevation of
      granulocytes in abdominal organs and fat after sc injections of 320 mg/kg; and 2)
      occasional wasting of skin over the injection site in female B6D2F1 but not male
      C3H/HeN mice. Significant weight loss (6%) was observed after sc injections of
      320 mg/kg but not 160 or 80 mg/kg. When male C3H/HeN mice were injected sc with
      AED at doses of 0-200 mg/kg 24 h before whole body gamma-irradiation (9 Gy), a
      significant improvement in survival was observed at doses as low as 5 mg/kg. Oral
      administration of AED produced significant survival enhancement at a dose of 1600
      mg/kg. We conclude that the radioprotective efficacy of AED is accompanied by low
      toxicity.

PMID- 12510794
TI  - Immunomodulatory effect of glutoxim on some activities of isolated human
      neutrophils and in whole blood.
AB  - Activity of Glutoxim, a sulfur-containing hexapeptide with immunomodulating
      effect on lymphocytes, was studied on human neutrophils. Commercial available
      agent containing the substance, Glutoxim, was used. At the doses of 1, 3, 6 or
      100 microg/mL the drug stimulated the superoxide anion and hypochlorous acid
      generation in resting neutrophils but inhibited them in cells stimulated with
      zymosan or PMA. The only inhibiting effect was observed on nitric oxide
      production in LPS-stimulated RAW 264.7 cells. The drug also influenced neutrophil
      chemotaxis showing chemoattractant activity on cells and inhibiting fMLP-induced
      chemotaxis. These effects on neutrophils confirm and extend range of Glutoxim
      immunomodulating abilities.

PMID- 12510795
TI  - Alterations of neutrophil functions in foundry and pottery workers.
AB  - To assess the immune competence of workers occupationally exposed to mainly
      silica, neutrophil functions such as the chemotactic and oxidative burst activity
      in foundry and pottery workers were evaluated. The chemotactic activity was
      examined in 22 foundry and 10 pottery workers and oxidative burst activity of
      neutrophils were determined in 22 foundry and 6 pottery workers. Healthy subjects
      of comparable age, sex, and smoking habits and with no history of silica exposure
      were used as the control groups. Chemotaxis was carried out in Boyden chambers
      using Zymosan activated serum as chemotactic stimulus. Oxidative burst activity
      was measured using nitroblue tetrazolium (NBT) dye reduction test. Both
      neutrophil functions were significantly reduced in silica-exposed foundry and
      pottery workers (p < 0.001) compared to controls suggesting that human chronic
      exposure mainly to silica and other chemicals originated from foundry and pottery
      settings may diminish neutrophil functions in humans.

PMID- 12510796
TI  - Hemopoiesis-stimulating effects and enhanced survival of irradiated mice after
      peroral or intraperitoneal administration of ultrafiltered pig leukocyte extract
      (UPLE, IMUNOR).
AB  - Ultrafiltered pig leukocyte extract (UPLE, IMUNOR, ImunomedicA, Usti nad Labem,
      Czech Republic) administered perorally (p.o.) or intraperitoneally (i.p.)
      enhanced recovery of the pool of granulocyte-macrophage hemopoietic progenitor
      cells (GM-CFC) in the bone marrow of normal or sublethally irradiated mice and
      increased survival of mice exposed to a lethal radiation dose. In experiments in
      vitro, sera of mice treated with UPLE p.o. or i.p. induced GM-CFC colony
      formation in cultures of normal mouse bone marrow cells, i.e., produced colony
      stimulating activity (CSA). UPLE alone did not induce GM-CFC colony growth, i.e.,
      had no CSA. When UPLE alone or sera of mice administered UPLE p.o. or i.p. were
      added to bone marrow cultures containing suboptimal concentration of recombinant
      mouse interleukin-3 (rmIL-3), both UPLE and the sera increased the counts of GM
      CFC colonies in comparison with cultures containing only rmIL-3, i.e., produced
      co-stimulating activity (CoSA). Based on the findings obtained in vitro, it can
      be hypothesized that the described CSA and CoSA of UPLE may play a role also
      under in vivo conditions; enhancement of the recovery of hemopoiesis suppressed
      by ionizing radiation may be due to co-operation of the stimulatory effects of
      UPLE with the action of cytokines endogenously produced in irradiated tissues.

PMID- 12510797
TI  - Fish immunology. I. Binding and engulfment of Candida albicans by erythrocytes of
      rainbow trout (Salmo gairdneri Richardson).
AB  - The role of fish erythrocytes (FE) as phagocytic cells has poorly been
      investigated, until now. Here, we have focussed our attention on the interplay
      between rainbow trout (Salmo gairdneri Richardson) erythrocytes and Candida
      albicans (CA). At the same time, the intervention of autologous head kidney
      macrophages (MO) in the CA processing by FE has been studied. Data show that CA
      particles bind to FE, which, in turn, are able to engulf but not kill them. In
      the presence of MO, a decrease of FE with bound CA occurs and, in some
      microscopic images, FE form rosettes with MO. Phagocytosis of CA is higher in
      rosetting MO than in non-rosetting ones. According to our findings, it appears
      that FE represent a reservoir of engulfed CA and rosetting is an efficacious
      phenomenon of presentation of pathogens to MO, where an effective clearance of
      them can take place.

PMID- 12510798
TI  - Fish immunology. II. Morphologycal and cytochemical characterization and
      phagocytic activities of head kidney macrophages from rainbow trout (Salmo
      gairdneri Richardson).
AB  - In Salmo gairdneri Richardson trouts, a comparison was made between macrophages
      (MO) derived from head kidney and peripheral blood monocytes. Morphologically and
      cytochemically no differences were observed between these two types of
      mononucleated cells. On the other hand, in parallel studies the ability of trout
      erythrocytes to engulf Candida albicans (CA) was evaluated and compared to the MO
      phagocytosis. In erythrocytes, engulfment is preceded by binding to CA and cell
      membrane invagination, while this was not the case for MO. Finally, MO stimulated
      with lipopolysaccharides (LPS) did not modify their phagocytic capacities, thus
      suggesting a lack of LPS receptors or a tolerance to LPS.

PMID- 12510799
TI  - Costs and strategies in minority recruitment for osteoporosis research.
AB  - To meet expectations for the participation of minority populations in research,
      we committed to enroll 140 minority subjects in addition to a random sample of
      Olmsted County, Minnesota residents (90% white) for a study of risk factors for
      age-related bone loss and fractures. We successfully enrolled 597 additional
      minority subjects but encountered specific problems with respect to
      identification of potential subjects, recruitment, obtaining informed consent,
      transportation to the study site, and collecting study data. These problems were
      resolved by observing the tenets of outreach to a diverse study population,
      namely (1) understand the target population; (2) establish explicit recruitment
      goals; (3) agree on research plans between study staff and minority communities;
      (4) continuously evaluate the recruitment process; and (5) maintain lines of
      communication. Success depended especially on the recruitment of cultural
      advisors from the different ethnic groups. These special efforts increased the
      recruitment cost substantially; the total expense of $122,000 for recruiting 550
      Asian, Hispanic, and Somali subjects was almost 5-fold higher than the $26,000
      required to recruit 699 mostly white study subjects from the population who were
      contacted by mail. Although it is not impossible to recruit minority subjects,
      investigators (and grant reviewers) should recognize that significant resources
      are required to gain access to ethnic communities for research. These results
      should contribute to more realistic budgets for recruiting minority subjects into
      clinical research studies.

PMID- 12510800
TI  - The effect of teriparatide [human parathyroid hormone (1-34)] therapy on bone
      density in men with osteoporosis.
AB  - Teriparatide [rhPTH(1-34)] increases bone mineral density and reduces the risk of
      vertebral fracture in women. We randomized 437 men with spine or hip bone mineral
      density more than 2 SD below the young adult male mean to daily injections of
      placebo, teriparatide 20 microg, or teriparatide 40 microg. All subjects also
      received supplemental calcium and vitamin D. The study was stopped after a median
      duration of 11 months because of a finding of osteosarcomas in rats in routine
      toxicology studies. Biochemical markers of bone formation increased early in the
      course of therapy and were followed by increases in indices of osteoclastic
      activity. Spine bone mineral density was greater than in placebo subjects after 3
      months of teriparatide therapy, and by the end of therapy it was increased by
      5.9% (20 microg) and 9.0% (40 microg) above baseline (p < 0.001 vs. placebo for
      both comparisons). Femoral neck bone mineral density increased 1.5% (20 microg; p
      = 0.029) and 2.9% (40 microg; p < 0.001), and whole body bone mineral content
      increased 0.6% (20 microg; p = 0.021) and 0.9% (40 microg;p = 0.005) above
      baseline in the teriparatide subjects. There was no change in radial bone mineral
      density in the teriparatide groups. Bone mineral density responses to
      teriparatide were similar regardless of gonadal status, age, baseline bone
      mineral density, body mass index, smoking, or alcohol intake. Subjects
      experienced expected changes in mineral metabolism. Adverse events were similar
      in the placebo and 20-microg groups, but more frequent in the 40-microg group.
      This study shows that teriparatide treatment results in an increase in bone
      mineral density and is a potentially useful therapy for osteoporosis in men.

PMID- 12510801
TI  - The skeletal response to teriparatide is largely independent of age, initial bone
      mineral density, and prevalent vertebral fractures in postmenopausal women with
      osteoporosis.
AB  - In a recent study of women with postmenopausal osteoporosis, treatment with
      teriparatide for a median of 19 months increased bone mineral density and
      decreased the risk of vertebral and nonvertebral fractures. Using the same
      cohort, the current study evaluated the relationship between these therapeutic
      effects and the patient's baseline age, vertebral bone mineral density, and
      prevalent vertebral fractures. In women over 65 years of age, treatment resulted
      in a greater increase in vertebral bone mineral density than in younger women
      (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the
      relative risk reduction for vertebral fractures (treatment-by-age interaction, p
      = 0.558). In women receiving placebo (with calcium and vitamin D), there was an
      inverse relationship between baseline vertebral bone mineral density and
      vertebral fracture risk. When compared across bone mineral density tertiles, the
      effects of teriparatide on the relative risk for developing new vertebral
      fractures and increase in vertebral bone mineral density did not differ
      significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment
      significantly decreased vertebral fracture risk in patients with a vertebral bone
      mineral density T score of less than -33 or a score between -2.1 and -3.3 (p <
      0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture
      risk in the group with a T score greater than -2.1 (p = 0.115). Placebo-treated
      women with two or more prevalent vertebral fractures had a significantly greater
      risk of developing new vertebral fractures than women with zero or one prevalent
      vertebral fracture (p < 0.001). When compared within prevalent vertebral fracture
      subgroups, the effects of teriparatide on the relative risk for developing new
      vertebral fractures were similar. The results of this study indicate that
      teriparatide offers clinical benefit to patients across a broad range of age and
      disease severity.

PMID- 12510802
TI  - The dynamic mobility of vertebral compression fractures.
AB  - We have observed that some osteoporotic vertebral compression fractures (VCFs)
      are mobile. The purpose of this report was to document the existence of dynamic
      fracture mobility, estimate the frequency of dynamic mobility in patients
      referred for vertebroplasty, define the magnitude and nature of dynamic mobility,
      and consider the implications of the dynamic mobility of osteoporotic VCFs. This
      was a prospective radiographic analysis of 41 consecutive patients with 65 VCFs
      who underwent vertebroplasty. Preoperative standing lateral radiographs of the
      fractured vertebrae were compared with supine cross-table lateral radiographs to
      determine the presence or absence of dynamic mobility. Postoperative standing
      lateral radiographs were evaluated to document fracture mobility and assess final
      vertebral height restoration. Radiographs were manually digitized to calculate
      vertebral body morphometrics. Dynamic fracture mobility was demonstrated in 44%
      of patients (35% of treated vertebrae) who underwent vertebroplasty.
      Postoperatively, in mobile fractures, average anterior vertebral height increased
      106% compared with initial fracture height (absolute increase, 8.41 +/- 0.4 mm).
      Mean lateral vertebral area increased from 48% to 80% of normal, and kyphotic
      angle decreased 40%. Mobile fractures dominated at the thoracolumbar junction.
      Intravertebral clefts were defined and identified in every mobile fracture and
      were absent from every nonmobile (fixed) fracture. This radiographic series
      documents the previously unrecognized occurrence of dynamic fracture mobility in
      many osteoporotic VCFs. Fracture mobility can be substantial and clinically
      significant. Any intervention that claims vertebral height restoration must
      control for the occurrence of dynamic fracture mobility.

PMID- 12510803
TI  - Ca2+ signaling mediated by IP3-dependent Ca2+ releasing and store-operated Ca2+
      channels in rat odontoblasts.
AB  - In the phospholipase-C (PLC) signaling system, Ca2+ is mobilized from
      intracellular Ca2+ stores by an action of inositol 1,4,5-trisphosphate (IP3). The
      depletion of IP3-sensitive Ca2+ stores activates a store-operated Ca2+ entry
      (SOCE). However, no direct evidence has been obtained about these signaling
      pathways in odontoblasts. In this study, we investigate the characteristics of
      the SOCE and IP3-mediated Ca2+ mobilizations in rat odontoblasts using fura-2
      microfluorometry and a nystatin-perforated patch-clamp technique. In the absence
      of extracellular Ca2+ ([Ca2+]o), thapsigargin (TG) evoked a transient rise in
      intracellular Ca2+ concentration ([Ca2+]i). After TG treatment to deplete the
      store, the subsequent application of Ca2+ resulted in a rapid rise in [Ca2+]i
      caused by SOCE. In the absence of TG treatment, no SOCE was evoked. The Ca2+
      influx was dependent on [Ca2+]o (KD = 1.29 mM) and was blocked by an IP3 receptor
      inhibitor, 2-aminoethoxydiphenyl borate (2-APB), as well as La3+ in a
      concentration-dependent manner (IC50 = 26 microM). In TG-treated cells, an
      elevation of [Ca2+]o from 0 to 2.5 mM elicited an inwardly rectifying current at
      hyperpolarizing potentials with a positive reversal potential. The currents were
      selective for Ca2+ over the other divalent cations (Ca2+ > Ba2+ > Sr2+ >> Mn2+).
      In the absence of [Ca2+]o, carbachol, bradykinin, and 2-methylthioadenosine
      5'triphosphate activated Ca2+ release from the store; these were inhibited by 2
      APB. These results indicate that odontoblasts possessed Ca2+ signaling pathways
      through the activation of store-operated Ca2+ channels by the depletion of
      intracellular Ca2+ stores and through the IP3-induced Ca2+ release activated by
      PLC-coupled receptors.

PMID- 12510804
TI  - Nitric oxide promotes infectious bone resorption by enhancing cytokine-stimulated
      interstitial collagenase synthesis in osteoblasts.
AB  - This experiment was undertaken to determine the role of macrophage-derived nitric
      oxide (NO) in mediating lipopolysaccharide (LPS)-induced bone resorption by using
      an in vitro co-culture system and an in vivo model of infectious bone resorption.
      Our results demonstrated that LPS stimulated the expression of inducible nitric
      oxide synthase (iNOS) and tumor necrosis factor (TNF)-a mRNAs and nitrite
      synthesis in the J774 mouse macrophage cell line but not in the UMR-106 (rat) and
      MC3T3-E1 (mouse) osteoblast cell lines. Conditioned media (CM) from LPS
      stimulated J774 triggered only low to moderate levels of iNOS mRNAs in MC3T3-E1
      and a trivial effect in UMR-106. On the other hand, CM induced matrix
      metalloproteinase-1 (MMP-1) gene expression in both osteoblast cell lines. The
      NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) did not alter this effect in
      MC3T3-E1 and UMR-106, whereas TNF-a antibody diminished the CM-induced MMP-1 gene
      expression in both cell lines. Interestingly, SNAP, a NO donor, although by
      itself is not a MMP-1 stimulator for UMR-106, augmented the TNF-alpha-stimulated
      MMP-1 mRNA production in UMR-106. In a J774/UMR-106 co-culture system, LPS
      stimulated significant MMP-1 gene expression in UMR-106, and this upregulation
      was abolished by L-NMMA and TNF-alpha antibodies. Immunohistochemical analysis in
      a rat model of infectious bone resorption (periapical lesion) showed co
      distributions of iNOS+ macrophages and MMP-1+ osteoblasts around the osteolytic
      areas. Administration of L-NMMA markedly reduced the extent of bone loss and the
      percentage of MMP-1-synthesizing osteoblasts. These data suggest that NO derived
      from macrophages after LPS stimulation may enhance bone loss by augmenting the
      cytokine-induced MMP-1 production in osteoblasts.

PMID- 12510805
TI  - Induction of human osteoprogenitor chemotaxis, proliferation, differentiation,
      and bone formation by osteoblast stimulating factor-1/pleiotrophin:
      osteoconductive biomimetic scaffolds for tissue engineering.
AB  - The process of bone growth, regeneration, and remodeling is mediated, in part, by
      the immediate cell-matrix environment. Osteoblast stimulating factor-1 (OSF-1),
      more commonly known as pleiotrophin (PTN), is an extracellular matrix-associated
      protein, present in matrices, which act as targets for the deposition of new
      bone. However, the actions of PTN on human bone progenitor cells remain unknown.
      We examined the effects of PTN on primary human bone marrow stromal cells
      chemotaxis, differentiation, and colony formation (colony forming unit
      fibroblastic) in vitro, and in particular, growth and differentiation on three
      dimensional biodegradable porous scaffolds adsorbed with PTN in vivo. Primary
      human bone marrow cells were cultured on tissue culture plastic or poly(DL-lactic
      acid-co-glycolic acid) (PLGA; 75:25) porous scaffolds with or without addition of
      recombinant human PTN (1 pg-50 ng/ml) in basal and osteogenic conditions.
      Negligible cellular growth was observed on PLGA scaffold alone, generated using a
      super-critical fluid mixing method. PTN (50 microg/ml) was chemotactic to human
      osteoprogenitors and stimulated total colony formation, alkaline phosphatase
      positive colony formation, and alkaline phosphatase-specific activity at
      concentrations as low as 10 pg/ml compared with control cultures. The effects
      were time-dependent. On three-dimensional scaffolds adsorbed with PTN, alkaline
      phosphatase activity, type I collagen formation, and synthesis of cbfa-1,
      osteocalcin, and PTN were observed by immunocytochemistry and PTN expression by
      in situ hybridization. PTN-adsorbed constructs showed morphologic evidence of new
      bone matrix and cartilage formation after subcutaneous implantation as well as
      within diffusion chambers implanted into athymic mice. In summary, PTN has the
      ability to promote adhesion, migration, expansion, and differentiation of human
      osteoprogenitor cells, and these results indicate the potential to develop
      protocols for de novo bone formation for skeletal repair that exploit cell-matrix
      interactions.

PMID- 12510806
TI  - A short pulse of mechanical force induces gene expression and growth in MC3T3-E1
      osteoblasts via an ERK 1/2 pathway.
AB  - Physiological mechanical loading is crucial for maintenance of bone integrity and
      architecture. We have calculated the strain caused by gravity stress on
      osteoblasts and found that 4-30g corresponds to physiological levels of 40-300
      microstrain. Short-term gravity loading (15 minutes) induced a 15-fold increase
      in expression of growth-related immediate early gene c-fos, a 5-fold increase in
      egr-1, and a 3-fold increase in autocrine bFGF. The non-growth-related genes EP
      1, TGF-beta, and 18s were unaffected by gravity loading. Short-term physiological
      loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation
      in a dose-dependent manner with maximum phosphorylation saturating at mechanical
      loading levels of 12g (p < 0.001) with no effect on total ERK. The
      phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical
      force. g-Loading did not activate P38 MAPK or c-jun N-terminal kinase (JNK).
      Additionally, a gravity pulse resulted in the localization of phosphorylated ERK
      1/2 to the nucleus; this did not occur in unloaded cells. The induction of c-fos
      was inhibited 74% by the MEK1/2 inhibitor U0126 (p < 0.001) but was not affected
      by MEK1 or p38 MAPK-specific inhibitors. The long-term consequence of a single 15
      minute gravity pulse was a 64% increase in cell growth (p < 0.001). U0126
      significantly inhibited gravity-induced growth by 50% (p < 0.001). These studies
      suggest that short periods of physiological mechanical stress induce immediate
      early gene expression and growth in MC3T3-E1 osteoblasts primarily through an ERK
      1/2-mediated pathway.

PMID- 12510807
TI  - Ascorbic acid induces collagenase-1 in human periodontal ligament cells but not
      in MC3T3-E1 osteoblast-like cells: potential association between collagenase
      expression and changes in alkaline phosphatase phenotype.
AB  - Ascorbic acid (AA) enhances osteoblastic differentiation by increasing collagen
      accumulation, which in turn, results in increased alkaline phosphatase (AP)
      expression in some osteogenic cells. However, in other cells, including human
      periodontal ligament (PDL) cells, additional osteoinductive agents are required
      for this response. To understand the potential basis for the maintenance of the
      AP phenotype of PDL cells exposed to AA, we examined the modulation of the tissue
      degrading matrix metalloproteinases (MMPs) and their inhibitors by AA in short
      term cell cultures. Early passage PDL cells in serum-free medium were exposed to
      AA for 5 days. The samples were analyzed for MMPs and their inhibitors, the
      tissue inhibitors of metalloproteinases (TIMPs), AP, collagen I(alpha1), and
      osteocalcin. We found that AA dose-dependently increased the expression of
      collagenase-1, and minimally TIMP-1, but not stromelysin-1 or TIMP-2.
      Additionally, AA caused substantial increases in levels of type I collagen. AA
      was unable to increase AP activity or osteocalcin messenger RNA in PDL cells.
      However, the cells retained the ability to show a significantly greater AP
      expression in high- versus low-density cultures, and increased osteocalcin as
      well as AP levels when cultured in the presence of dexamethasone. Moreover, in
      cells exposed to dexamethasone, increases in AP and osteocalcin were accompanied
      by a repression of collagenase-1 expression. In contrast to PDL cells, AA did not
      induce collagenase but produced a significant increase in AP expression in MC3T3
      E1 cells. These findings provide the first evidence that AA, by modulating both
      collagen and collagenase-1 expression in PDL cells, most likely contributes to a
      net matrix remodeling response in these cells. Furthermore, the relationship
      between changes in collagenase expression and alterations in AP activity in PDL
      and MC3T3-E1 cells suggests a potential role for collagenase in modulating the AP
      phenotype of cells with osteoblastic potential.

PMID- 12510808
TI  - Alendronate interacts with the inhibitory effect of 1,25(OH)2D3 on parathyroid
      hormone-related protein expression in human osteoblastic cells.
AB  - The bisphosphonate alendronate is a potent inhibitor of bone resorption by its
      direct action on osteoclasts. In addition, there is some data suggesting that
      alendronate could also inhibit bone resorption indirectly by interacting with
      osteoblasts. Parathyroid hormone-related protein (PTHrP) produced by osteoblasts
      and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] are regulators of bone remodeling,
      which have interrelated actions in these cells. In this study, we assessed
      whether alendronate can affect PTHrP expression in the presence or absence of
      1,25(OH)2D3 in human primary osteoblastic (hOB) cells from trabecular bone. Cell
      total RNA was isolated, and semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR) was carried out using human PTHrP-specific primers. PTHrP
      in the hOB cell-conditioned medium was analyzed by a specific immunoradiometric
      assay. We found that PTHrP mRNA and secreted PTHrP were maximally inhibited by
      10(-8) - 10(-6) M of 1,25(OH)2D3 treatment within 8-72 h in hOB cells.
      Alendronate (10(-14) - 10(-8) M) modified neither PTHrP mRNA nor PTHrP secretion,
      although it consistently abrogated the decrease in PTHrP production induced by
      1,25(OH)2D3 in these cells. On the other hand, alendronate within the same dose
      range did not affect either the vitamin D receptor (VDR) mRNA or osteocalcin
      secretion, with or without 1,25(OH)2D3, in hOB cells. The inhibitory effect of
      alendronate on the 1,25(OH)2D3-induced decrease in PTHrP in these cells was
      mimicked by the calcium ionophore A23187 (5 x 10-6 M), while it was eliminated by
      5 x 10(-5) M of nifedipine. Furthermore, although alendronate alone failed to
      affect [Ca2+]i in these cells, it stimulated [Ca2+]i after pretreatment of hOB
      cells with 10(-8) M of 1,25(OH)2D3, an effect that was abolished by 5 x 10(-5) M
      of nifedipine. These results show that alendronate disrupts the modulatory effect
      of 1,25(OH)2D3 on PTHrP production in hOB cells. Our findings indicate that an
      increase in calcium influx appears to be involved in the mechanism mediating this
      effect of alendronate.

PMID- 12510809
TI  - The ability of statins to inhibit bone resorption is directly related to their
      inhibitory effect on HMG-CoA reductase activity.
AB  - Statins, which are inhibitors of 3-hydroxy-3-glutaryl-coenzyme A (HMG-CoA)
      reductase, decrease the hepatic biosynthesis of cholesterol by blocking the
      mevalonate pathway. Nitrogen-containing bisphosphonate drugs also inhibit the
      mevalonate pathway, preventing the production of the isoprenoids, which
      consequently results in the inhibition of osteoclast formation and osteoclast
      function. Therefore, we hypothesized that statins could affect bone metabolism in
      vivo through effects on osteoclastic bone resorption. In vitro, cerivastatin
      inhibited the parathyroid hormone (PTH)-stimulated bone resorption. Using a panel
      of 40 statin analogs, which showed variable effects on HMG-CoA reductase
      activity, we found that the ability of compounds to inhibit bone resorption is
      directly related to HMG-CoA reductase activity. However, in the thyro
      parathyrodectomy (TPTX) model for bone resorption in the rat in vivo,
      cerivastatin did not prevent experimentally induced increases in bone resorption.
      The lack of effect of cerivastatin in this model is not related to a limited
      penetration of the target tissue (bone marrow), because a significant effect on
      HMG-CoA reductase activity was demonstrated in the total rat bone marrow cell
      extracts of rats posttreatment in vivo. Furthermore, cerivastatin inhibited
      protein prenylation in osteoclasts isolated from the rabbit bone marrow of
      rabbits after treatment in vivo. In contrast to other studies, none of the
      statins tested showed anabolic effects in parietal bone explant cultures. Taken
      together, we conclude that statins inhibit bone resorption in vitro, which
      correlates directly with the potency of the compounds for inhibition of HMG-CoA
      reductase activity. However, cerivastatin does not affect bone resorption in the
      rat TPTX model in vivo.

PMID- 12510810
TI  - In vitro demonstration of cell-to-cell interaction in growth plate cartilage
      using chondrocytes established from p53-/- mice.
AB  - Three clonal cell lines (MMR14, MMR17, and MMR32) were established from the
      costal cartilage derived from p53-/- mice. Expression profiles of cartilage
      related molecules in MMR14 and MMR17 were compatible with those in cells of the
      hypertrophic zone. Prolonged in vitro culture induced the expression of
      calcification-related genes in both cell lines, but calcified nodules were
      observed only in MMR14. The expression profile of cartilage-related molecules in
      MMR32 was compatible with that of cells in the perichondrium, with high
      expression levels of decorin, bone morphogenetic protein-3, and parathyroid
      hormone-related peptide (PTHrP). When MMR14 was co-cultured with an equal amount
      of MMR32 without direct contact, the nodule formation was completely inhibited,
      whereas no such inhibition was observed when MMR14 was co-cultured with MMR17,
      indicating that soluble factors produced by MMR32 were responsible for the
      inhibition. Blocking the effects of PTHrP by either antagonizing peptide or
      neutralizing antibody against PTHrP failed to rescue the inhibitory effects of
      MMR32, and no increase of the cyclic adenosine monophosphate production in MMR14
      was observed when co-cultured with MMR32, suggesting that soluble factors other
      than PTHrP produced by MMR32 were responsible for the inhibition of terminal
      differentiation of hypertrophic chondrocytes. This report is the first to show
      cell-to-cell interaction in the growth plate using cell lines, which will be
      useful material to investigate the regulatory mechanism of chondrocyte
      differentiation.

PMID- 12510811
TI  - Reduction of osteoclasts in a critical embryonic period is essential for
      inhibition of mouse tooth eruption.
AB  - Alveolar bone resorption by osteoclasts is essential for tooth eruption.
      Osteoclast-deficient Csfm(op) homozygous (op/op) mice, which lack functional
      macrophage colony-stimulating factor (M-CSF), suffer from osteopetrosis and
      completely lack tooth eruption. Although osteoclasts appear, and osteopetrosis is
      cured with age in op/op mice, tooth eruption is never seen. This fact suggests
      that there is a critical period when osteoclasts are required for tooth eruption.
      In this study, to detect the critical period, we administered an antagonistic
      antibody directed against c-Fms, a receptor for M-CSF, to inbred C57BL/6 mice for
      various periods. Administration of this antibody decreased tartrate-resistant
      acid phosphatase-positive (TRAP) osteoclasts, and incisor eruption was completely
      inhibited by continual administration of this antibody from embryonic day 15.5
      (E15.5) until postnatal day 12.5 (D12.5). A 1-day delay of this administration
      abolished the inhibition of incisor eruption. The number of TRAP-positive
      osteoclasts was significantly reduced between E16.5 and E18.5 in the mice treated
      with antibody from E15.5 compared with those treated from E16.5. These results
      indicate that this period, during which the number of osteoclasts decreases
      significantly, is critical for inhibiting incisor eruption in C57BL/6 mice.

PMID- 12510812
TI  - Orientation of mineral crystallites and mineral density during skeletal
      development in mice deficient in tissue nonspecific alkaline phosphatase.
AB  - Tissue nonspecific alkaline phosphatase (TNALP) is thought to play an important
      role in mineralization processes, although its exact working mechanism is not
      known. In the present investigation we have studied mineral crystal
      characteristics in the developing skeleton of TNALP-deficient mice. Null mutants
      (n = 7) and their wild-type littermates (n = 7) were bred and killed between 8
      and 22 days after birth. Skeletal tissues were processed to assess mineral
      characteristics (small angle X-ray scattering, quantitative backscattered
      electron imaging), and to analyze bone by light microscopy and immunolabeling.
      The results showed a reduced longitudinal growth and a strongly delayed
      epiphyseal ossification in the null mutants. This was accompanied by disturbances
      in mineralization pattern, in that crystallites were not orderly aligned with
      respect to the longitudinal axis of the cortical bone. Among the null mutants, a
      great variability in the mineralization parameters was noticed. Also,
      immunolabeling of osteopontin (OPN) revealed an abnormal distribution pattern of
      the protein within the bone matrix. Whereas in the wild-type animals OPN was
      predominantly observed in cement and reversal lines, in the null mutants, OPN was
      also randomly dispersed throughout the nonmineralized matrix, with focal
      densities. In contrast, the distribution pattern of osteocalcin (OC) was
      comparable in both types of animals. It is concluded that ablation of TNALP
      results not only in hypomineralization of the skeleton, but also in a severe
      disorder of the mineral crystal alignment pattern in the corticalis of growing
      long bone in association with a disordered matrix architecture, presumably as a
      result of impaired bone remodeling and maturation.

PMID- 12510813
TI  - Intravenous neridronate in adults with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a heritable disease of connective tissue,
      characterized by increased bone fragility. Bisphosphonates currently seems to be
      the most promising therapy, at least in children. We tested IV neridronate, an
      amino-bisphosphonate structurally similar to alendronate and pamidronate in
      adults with OI. Twenty-three men and 23 premenopausal women with OI were
      randomized to either iv neridronate (100 mg infused intravenously for 30 minutes
      every 3 months) or no treatment with a ratio of 2 to 1. Control patients were
      given the same bisphosphonate therapy at the end of the first year. Clinical
      evaluation included bone densitometry measurements using dual energy X-ray
      absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and
      radiographs of the spine taken at baseline and after 12 and 24 months of follow
      up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/-
      3.9%, respectively, within the first 12 months of treatment, whereas small
      insignificant changes were observed in the control group. During the second year
      of follow-up, additional 3.91% and 1.49% increases were observed at the spine and
      hip, respectively. Markers of skeletal turnover significantly fell during
      neridronate treatment. Fracture incidence during neridronate treatment was
      significantly lower than before therapy and compared with controls. Neridronate
      iv infusions, administered quarterly, significantly increase bone mineral density
      and lowered the risk of clinical fracture in adults with OI. Bisphosphonate
      therapy seems to provide clinical benefits, not only to children with OI, but
      also to adult patients.

PMID- 12510814
TI  - Hadju-Cheney syndrome: response to therapy with bisphosphonates in two patients.
AB  - Hadju-Cheney syndrome is characterized by short stature, distinctive facies, and
      a slowly progressive skeletal dysplasia including acro-osteolysis. Autosomal
      dominant inheritance is typical, but the genetic defect and molecular
      pathogenesis of the syndrome are unknown. Osteoporosis with atraumatic fracture
      is a frequent finding, and previous studies have documented biochemical and
      morphometric evidence of high bone turnover. Here, we report the clinical details
      and response to therapy with bisphosphonates in two patients (mother and son)
      with Hadju-Cheney syndrome and postulate that osteoclast-mediated bone resorption
      is important in the generalized osteoporosis commonly associated with this
      condition.

PMID- 12510815
TI  - A novel immunoassay for the determination of tartrate-resistant acid phosphatase
      5b from rat serum.
AB  - Osteoclasts secrete tartrate-resistant acid phosphatase 5b (TRACP 5b) into the
      circulation. We have developed an immunoassay for the determination of rat TRACP
      5b activity. Intra-assay variation of the immunoassay was 4.5%, interassay
      variation was 3.8%, dilution linearity was 104.6 +/- 7.6%, and recovery of
      recombinant rat TRACP was 99.1 +/- 5.8%. We studied serum TRACP 5b as a marker of
      bone resorption using orchidectomized (ORC) rats as a model for osteoporosis and
      age-matched sham-operated rats as controls in a 6-month study. After the
      operation, trabecular bone mineral density decreased significantly more in the
      ORC group than in the sham group, whereas cortical bone mineral density increased
      similarly in both groups. Serum TRACP 5b activity was significantly elevated
      within the first week after ORC, returned to the control level in the third week,
      and was not increased above the sham level at any of the later time points. At 6
      months, trabecular bone volume was 80% lower in ORC rats than in controls.
      Osteoclast number per trabecular bone perimeter was slightly increased, but the
      absolute number of osteoclasts in trabecular bone was significantly decreased.
      These results suggest that absolute bone resorption is increased within the first
      week after ORC. Later, it is decreased because there is less bone to be resorbed.
      However, relative bone resorption (compared with the amount of remaining bone) is
      still increased, leading to further bone loss. We conclude that serum TRACP 5b is
      a useful marker for monitoring changes in the bone resorption rate in rat ORC
      model.

PMID- 12510816
TI  - Tower climbing exercise started 3 months after ovariectomy recovers bone strength
      of the femur and lumbar vertebrae in aged osteopenic rats.
AB  - To determine both the preventive and recovery effects of tower climbing exercise
      on mass, strength, and local turnover of bone in ovariectomized (OVX) rats, we
      carried out two experiments. In experiment I, 60 Sprague-Dawley rats, 12 months
      of age, were assigned to four groups: a Baseline Control, Sham-Operated
      Sedentary, OVX-Sedentary and OVX-Exercise rats. Rats voluntarily climbed a 200-cm
      tower to drink water from a bottle set at the top. At 3 months, OVX elevated both
      the femoral cortex and lumbar trabecular turnover, leading to a reduction in bone
      mass and strength. However, in OVX-Exercise rats, those values were maintained at
      the same level as in the Sham-Sedentary rats. Thus, the climbing exercise,
      started after 3 days of OVX, prevented OVX-induced cortical and trabecular bone
      loss by depressing turnover elevation. After confirming the preventive effect, we
      evaluated the recovery effect of exercise. In experiment II, 90 Sprague-Dawley
      rats, 12 months of age, were assigned to six groups: a Baseline control, two
      groups of Sham-Operated Sedentary and OVX-Sedentary, and OVX-Exercise rats. The
      exercise started 3 months after the OVX operation. At 3 months, OVX increased the
      trabecular bone formation rate and osteoclast surface, leading to a decrease in
      compressive strength. In the midfemur, the cross-sectional area, moment of
      inertia, and bending load values decreased. At 6 months, in the OVX-Exercise
      rats, the parameters of breaking load in both the lumbar and midfemur, lumbar
      bone mass, and the total cross-sectional area recovered to the same levels as
      those in the Sham-Sedentary rats. However, the cortical bone area did not
      recover. Periosteal bone formation increased, while endosteal bone formation
      decreased. These results showed that the climbing exercise had both a preventive
      and recovery effect on bone strength in OVX rats. In the mid-femur, effects on
      bone formation were site-specific, and the cross-sectional morphology was
      improved without an increase in cortical bone area, supporting cortical drift by
      mechanical stimulation.

PMID- 12510817
TI  - The structural and hormonal basis of sex differences in peak appendicular bone
      strength in rats.
AB  - To identify the structural and hormonal basis for the lower incidence of
      fractures in males than females, sex differences in femoral mid-shaft geometry
      and breaking strength were studied in growth hormone (GH)-replete and -deficient
      male and female rats. Sexual dimorphism appeared during growth. Cortical
      thickening occurred almost entirely by acquisition of bone on the outer
      (periosteal) surface in males and mainly on the inner (endocortical) surface in
      females. By 8 months of age, males had 22% greater bone width and 33% greater
      breaking strength than females. Gonadectomy (Gx) at 6 weeks reduced sex
      differences in bone width to 7% and strength to 21% by halving periosteal bone
      formation in males and doubling it in females. Gx had no net effect on the
      endocortical surface in males but abolished endocortical bone acquisition in
      females. GH deficiency halved periosteal bone formation and had no net effect on
      the endocortical surface in males, but abolished bone acquisition on both
      surfaces in females, leaving males with 17% greater bone width and 44% greater
      breaking strength than females. Sex hormone deficiency produces greater bone
      fragility in males than females by removing a stimulator of periosteal growth in
      males and removing an inhibitor of periosteal growth in females. GH deficiency
      produces less bone fragility in males than females because males retain androgen
      dependent periosteal bone formation while bone acquisition on both surfaces is
      abolished in females. Thus, periosteal growth is independently and additively
      stimulated by androgens and GH in males, inhibited by estrogen, and stimulated by
      GH in females. The hormonal regulation of bone surfaces establishes the amount
      and spatial distribution of bone and so the sexual dimorphism in its strength.

PMID- 12510818
TI  - Regional specificity of exercise and calcium during skeletal growth in girls: a
      randomized controlled trial.
AB  - Combining exercise with calcium supplementation may produce additive or
      multiplicative effects at loaded sites; thus, we conducted a single blind,
      prospective, randomized controlled study in pre- and early-pubertal girls to test
      the following hypotheses. (1) At the loaded sites, exercise and calcium will
      produce greater benefits than exercise or calcium alone. (2) At non-loaded sites,
      exercise will have no benefit, whereas calcium with or without exercise will
      increase bone mass over that in exercise alone or no intervention. Sixty-six
      girls aged 8.8 +/- 0.1 years were randomly assigned to one of four study groups:
      moderate-impact exercise with or without calcium or low-impact exercise with or
      without calcium. All participants exercised for 20 minutes, three times a week
      and received Ca-fortified (434 +/- 19 mg/day) or non-fortified foods for 8.5
      months. Analysis of covariance (ANCOVA) was used to determine interaction and
      main effects for exercise and calcium on bone mass after adjusting for baseline
      bone mineral content and growth in limb lengths. An exercise-calcium interaction
      was detected at the femur (7.1%, p < 0.05). In contrast, there was no exercise
      calcium interaction detected at the tibia-fibula; however, there was a main
      effect of exercise: bone mineral content increased 3% more in the exercise than
      non-exercise groups (p < 0.05). Bone mineral content increased 2-4% more in the
      calcium-supplemented groups than the non-supplemented groups at the humerus
      (12.0% vs. 9.8%, respectively, p < 0.09) and radius-ulna (12.6% vs. 8.6%,
      respectively, p < 0.01). In conclusion, greater gains in bone mass at loaded
      sites may be achieved when short bouts of moderate exercise are combined with
      increased dietary calcium, the former conferring region-specific effects and the
      latter producing generalized effects.

PMID- 12510819
TI  - Osteosarcoma of bone in apatient with primary hyperparathyroidism: a case report.
AB  - A 69-year-old woman was diagnosed with a malignant tumor of the right proximal
      femur. She had primary hyperparathyroidism and chronic elevation of parathyroid
      hormone levels (PTH > 1,000 pg/ml). She underwent resection of the bone lesion;
      histological analysis showed a high-grade fibroblastic osteosarcoma. In addition,
      she underwent curative resection of a large left superior parathyroid adenoma. To
      our knowledge, this is the third reported clinical case of osteosarcoma arising
      in association with hyperparathyroidism.

PMID- 12510820
TI  - Effect of pregnancy on bone mineral density and biochemical markers of bone
      turnover in a patient with juvenile idiopathic osteoporosis.
AB  - Juvenile idiopathic osteoporosis (JIO) is rare, presenting with vertebral
      fractures in the immediate prepubertal years; however, recovery is normally
      observed. We report the case of a 19-year-old pregnant woman previously diagnosed
      with JIO. She experienced three vertebral fractures in the third trimester of
      pregnancy. She delivered by caesarean section at 38 weeks gestation. Spinal bone
      mineral density decreased by 25%, hip bone mineral density by 10%, and forearm
      bone mineral density by 3% during pregnancy. Bone resorption markers, free
      pyridinoline and deoxypyridinoline (fPYD and fDPD), were elevated at baseline and
      markedly increased during pregnancy (fPYD/fDPD at 0, 10, 15, 20, and 28 weeks and
      immediately postpartum: 36.2/11.5, 52.9/15.8, 54.3/13.3, 51.1/13.3, 90/21.8, and
      95.6/22.7 nmol/mmol creatinine, respectively) The bone formation marker, bone
      specific alkaline phosphatase (BSAP), was within the reference range at baseline
      and increased in the third trimester. (BSAP at 0, 10, 15, 20, and 28 weeks and
      immediately postpartum: 20.5, 18.3, 17.7, 19.8, 26.9, and 30.0 U/liter,
      respectively). Parathyroid hormone (PTH) was measured by two methods to assess
      the possible effect of PTH fragments. PTH(1-84) (Roche) showed little change
      during the pregnancy, whereas the Nichols assay [(1-84) and(7-84) PTH fragment],
      revealed increases paralleling the changes in bone resorption. This young woman's
      bone turnover showed an exaggerated response to pregnancy, with bone resorption
      predominating over formation. PTH fragments may have partially mediated this
      effect.

PMID- 12510821
TI  - Highly sweet compounds of plant origin.
AB  - The demand for new alternative "low calorie" sweeteners for dietetic and diabetic
      purposes has increased worldwide. Although the currently developed and
      commercially used highly sweet sucrose substitutes are mostly synthetic
      compounds, the search for such compounds from natural sources is continuing. As
      of mid-2002, over 100 plant-derived sweet compounds of 20 major structural types
      had been reported, and were isolated from more than 25 different families of
      green plants. Several of these highly sweet natural products are marketed as
      sweeteners or flavoring agents in some countries as pure compounds, compound
      mixtures, or refined extracts. These highly sweet natural substances are reviewed
      herein.

PMID- 12510822
TI  - Biological significance of essential fatty acids/prostanoids/lipoxygenase-derived
      monohydroxy fatty acids in the skin.
AB  - The skin displays a highly active metabolism of polyunsaturated fatty acids
      (PUFA). Dietary deficiency of linoleic acid (LA), an 18-carbon (n-6) PUFA,
      results in characteristic scaly skin disorder and excessive epidermal water loss.
      Although arachidonic acid (AA), a 20-carbon (n-6) PUFA, is metabolized via
      cyclooxygenase pathway into predominantly prostaglandin E2 (PGE2) and PGF2alpha,
      the metabolism of AA via the 15-lipoxygenase (15-LOX) pathway, which is very
      active in skin epidermis and catalyzes the transformation of AA into
      predominantly 15S-hydroxyeicosatetraenoic acid (15S-HETE). Additionally, the 15
      LOX also metabolizes the 18-carbon LA into 13S-hydroxyoctadecadienoic acid (13S
      HODE), respectively. Interestingly, 15-LOX catalyzes the transformation of dihomo
      gamma-linolenic acid (DGLA), derived from dietary gamma-linolenic acid, to 15S
      hydroxyeicosatrienoic acid (15S-HETrE). These monohydroxy fatty acids are
      incorporated into the membrane inositol phospholipids which undergo hydrolytic
      cleavage to yield substituted-diacylglycerols such as 13S-HODE-DAG from 13S-HODE
      and 15S-HETrE-DAG from 15S-HETrE. These substituted-monohydroxy fatty acids
      seemingly exert anti-inflammatory/antiproliferative effects via the modulation of
      selective protein kinase C as well as on the upstream/down-stream nuclear MAP
      kinase/AP-1/apoptotic signaling events.

PMID- 12510823
TI  - Chemistry and biology of Ras farnesyltransferase.
AB  - Mutated forms of ras are found in many human tumors and the rate of incidence is
      significantly higher in colon and pancreatic cancers. The protein product from
      the ras oncogene is a small G-protein, p21(ras) (Ras) that is known to play a key
      role in the signal transduction cascade and cell differentiation and
      proliferation. Mutated Ras is unable to regulate itself and remains constantly
      activated, leading to uncontrolled cell growth. The function of Ras in signal
      transduction requires its location near the growth factor receptor at the cell
      membrane. However, Ras does not have a transmembrane domain. Ras requires
      farnesylation to increase its hydrophobicity and subsequent plasma membrane
      association for its transforming activity. This key post-translational
      modification is catalyzed by the enzyme Ras famesyltransferase (FTase), which
      transfers a famesyl group from farnesylpyrophosphate to the C-terminal cysteine
      of the Ras protein. The requirement has focused attention on FTase as a target
      for therapeutic intervention. Selective inhibition of FTase will prevent Ras
      protein from association with the plasma membrane, leading to a disruption of
      oncogenic Ras function.

PMID- 12510824
TI  - Airway mucus: its components and function.
AB  - The airway surface liquid (ASL), often referred to as mucus, is a thin layer of
      fluid covering the luminal surface of the airway. The major function of mucus is
      to protect the lung through mucociliary clearance against foreign particles and
      chemicals entering the lung. The mucus is comprised of water, ions, and various
      kinds of macromolecules some of which possess the protective functions such as
      anti-microbial, anti-protease, and anti-oxidant activity. Mucus glycoproteins or
      mucins are mainly responsible for the viscoelastic property of mucus, which is
      crucial for the effective mucociliary clearance. There are at least eight mucin
      genes identified in the human airways, which will potentially generate various
      kinds of mucin molecules. At present, neither the exact structures of mucin
      proteins nor their regulation are understood although it seems likely that
      different types of mucins are involved in different functions and might also be
      associated with certain airway diseases. The fact that mucins are tightly
      associated with various macromolecules present in ASL seems to suggest that the
      defensive role of ASL is determined not only by these individual components but
      rather by a combination of these components. Collectively, mucins in ASL may be
      compared to aircraft carriers carrying various types of weapons in defense of
      airbome enemies.

PMID- 12510825
TI  - Novel benzoylurea derivatives as potential antitumor agents; synthesis,
      activities and structure-activity relationships.
AB  - A series of pyrazoloxyphenyl benzoyl urea derivatives was designed and
      synthesized for cytotoxic evaluation as potential antitumor agents. The synthetic
      compounds were evaluated for in vitro cytotoxicity against five human tumor cell
      lines, including A-549, SKOV-3, SK-MEL-2, XF-498 and HCT-15. Among others,
      compound 11 exhibited 50-100 times greater antitumor activities than the
      commercial product, Cisplatin.

PMID- 12510826
TI  - Total synthesis of a norneolignan from Ratanhia radix.
AB  - The total synthesis of a norneolignan isolated from Ratanhia, 5-(3-hydroxypropyl)
      2-(2-methoxy-4'-hydroxyphenyl)benzofuran (8), is described. The key steps contain
      the one-pot reaction for a 2-arylbenzofuran 6 from methyl 3-(4
      hydroxyphenyl)propionate with 2-chloro-2-methylthio-(2'-methoxy-4'
      acetoxy)acetophenone (5) in the presence of ZnCl2, and reductive desulfurization
      of the resulting product 6.

PMID- 12510827
TI  - Synthesis and antiviral activity of novel exomethylene cyclopropyl pyrimidine
      nucleosides.
AB  - A series of novel exomethylene cyclopropyl nucleosides have been synthesized
      starting from Feist's acid. Classical nucleophilic substitution conditions
      (K2CO3, 18-crown-6) of the tosylate 2 as well as Mitsunobu reaction (DEAD, PPh3)
      of alcohol 1 with pyrimidine bases afforded a series of novel cyclopropyl
      nucleosides. Compound 4b displayed moderate anti-HBV activity without any
      cytotoxicity up to 100 microM.

PMID- 12510828
TI  - Synthesis and antifungal activity of 6,7-bis-[S-(aryl)thio]-5,8-quinolinediones.
AB  - 6,7-Bis-[S-(aryl)thio]-5,8-quinolinediones 4 and 5 were synthesized by the
      substitution of 6,7-dichloro-5,8-quinolinediones with appropriate arylthiols.
      Their antifungal activity were tested in vitro for their growth inhibitory
      activities against pathogenic fungi in comparison with flucytosine. The
      antifungal activities were significantly improved by S-(aryl)thio moieties of the
      compounds 4 and 5. The all tested compounds 4 and 5 showed generally good
      activities against C. albicans and A. niger ranging from 0.8 to 25 microg/ml.
      Among them, compounds 4d-4h and 5a-5c exhibited also good activities against C.
      krusei and C. tropicalis. The activities of compounds 4j and 4l were comparable
      to those of flucytosine against all tested fungi.

PMID- 12510829
TI  - Efficient macrocyclization for cyclicpeptide using solid-phase reaction.
AB  - Cyclicpeptides are important targets in peptide synthesis because of their
      interesting biological properties. Constraining highly flexible linear peptides
      by cyclization is one of the mostly widely used approaches to define the
      bioactive conformation of peptides. Cyclic peptides often have increased receptor
      affinity and metabolic stability over their linear counterparts. We carried out
      virtual screening experiment via docking in order to understand the interaction
      between HLE-Human Leukocyte Elastase and ligand peptide and to identify the
      sequence that can be a target in various ligand peptides. We made cyclic peptides
      as a target base on Met-Ile-Phe sequence having affinity for ligand and receptor
      active site docking. There are three ways to cyclize certain sequences of amino
      acids such as Met-Ile-Phe-Gly-Ile. First is head-to-tail cyclization method,
      linking between N-terminal and C-terminal. Second method utilizes amino acid side
      chain such as thiol functional group in Cys, making a thioether bond. The last
      one includes an application of resin-substituted amino acids in solid phase
      reaction. Among the three methods, solid phase reaction showed the greatest
      yield. Macrocyclization of Fmoc-Met-Ile-Phe-Gly-Ile-OBn after cleavage of Fmoc
      protection in solution phase was carried out to give macrocyclic compound 5 in
      about 7% yield. In the contrast with solution phase reaction, solid phase
      reaction for macrocyclization of Met-Ile-Phe-Gly-Ile-Asp-Tentagel in normal
      concentrated condition gave macrocyclic compound 7 in more than 35% yield.

PMID- 12510830
TI  - Flexible docking of an acetoxyethoxymethyl derivative of thiosemicarbazone into
      three different species of dihydrofolate reductase.
AB  - Dihydrofolate reductases (DHFR) of human, Candida albicans and E coli were docked
      with their original ligands of X-ray crystal complex using QXP (Quick eXPlore), a
      docking program. Conditions to reproduce the crystal structures within the root
      mean square deviation (rmsd) of 2.00 A were established. Applying these
      conditions, binding modes and species-specificities of a novel antibacterial
      compound, N4-(2-acetoxyethoxymethyl)-2-acetylpyridine thiosemicarbazone (AATSC),
      were studied. As the results, the docking program reproduced the crystal
      structures with average rmsd of six ligands as 0.91 A ranging from 0.49 to 1.45
      A. The interactions including the numbers of hydrogen bonds and hydrophobic
      interactions were the same as the crystal structures and superposition of the
      crystal and docked structures almost coincided with each other. For AATSC, the
      results demonstrated that it could bind to either the substrate or coenzyme sites
      of DHFR in all three species with different degrees of affinity. It confirms the
      experimentally determined kinetic behavior of uncompetitive inhibition against
      either the inhibitor or the coenzyme. The docked AATSC overlapped well with the
      original ligands and major interactions were consistent with the ones in the
      crystal complexes. The information generated from this work should be useful for
      future development of antibacterial and antifungal agents.

PMID- 12510831
TI  - Inhibitory effect of corynoline isolated from the aerial parts of Corydalis
      incisa on the acetylcholinesterase.
AB  - In the course of screening Korean natural products for acetylcholinesterase
      (AChE) inhibitory activity, it was found that a methanolic extract of the aerial
      parts of Corydalis incisa (Papaveraceae) showed significant inhibitory effects on
      AChE. Corynoline isolated from this plant inhibited AChE activity in a dose
      dependent manner, and the IC50 value of corynoline was 30.6 microM. The AChE
      inhibitory activity of corynoline was reversible and noncompetitive.

PMID- 12510832
TI  - Structure of three new terpenoids, spiciformisins a and b, and monocyclosqualene,
      isolated from the herbs of Ligularia fischeri var. spiciformis and cytotoxicity.
AB  - The diethylether fraction from the leaves extract of Ligularia fischeri var.
      spiciformis (Compositae) was subjected to silica gel column chromatography and
      yielded three new terpenoids named spiciformisin a (1), spiciformisin b (3), and
      monocyclosqualene (2). Acyclic diterpenes, spiciformisin a and -b, were
      established as 3,7,11,15-tetramethyl-1,3(20)-hexadecadiene and 3,7,11,15
      tetramethyl-1,3,6,10,14-hexadecapentaene (IUPAC), respectively. A monocyclic
      triterpene, monocyclosqualene, were determined as [3,8,12,16,16-pentamethyl
      (3,7,11,15-hexadecatetraenyl)]-3,3,5-trimethyl-1-cyclohexene. The structures were
      determined on the basis of NMR and MS analysis. Spiciformicin b showed potent
      cytotoxicity (IC50, <9.7 microg/ml against HL-60) in contrast to no cytotoxicity
      (IC50, >200 microg/ml against HL-60 cells) of spiciformicin a with a cis
      conjugated dienyl diexomethylene.

PMID- 12510833
TI  - Constituents of the fruits and leaves of Euodia daniellii.
AB  - Four flavonoid glycosides, flavaprin (7), evodioside B (8), vitexin (11), and
      hesperidin (12), as well as the coumarins bergapten (1), xanthotoxin (2), and
      isopimpinellin (3), the lignan simplexoside (10), the steroids beta-sitosterol
      (4) and daucosterol (5), the limonoids isolimonexic acid (6) and limonin (9), and
      uracil (13) and myo-inositol (14) have been isolated from Euodia daniellii. The
      structures of these compounds were established from spectral data. Among the
      isolates, bergapten showed cyclooxygenase-2 inhibitory activity with an IC50
      value of 6.2 microg/ml. Flavonoids isolated from this plant exhibited no
      cytotoxic activity against the human tumor cell lines, A549, SKOV-3, SKMEL-2,
      XF498, and HCT15.

PMID- 12510834
TI  - A new lupane-triterpene glycoside from the leaves of Acanthopanax gracilistylus.
AB  - A new and two known lupane-triterpene glycosides were isolated from the hot MeOH
      fraction of the leaves of Acanthopanax gracilistylus W. W. Smith. Based on the
      physical properties and spectroscopic data, their chemical structures were
      determined as acankoreoside A (1), acankoreoside D (2), and 3alpha-hydroxy-lup-23
      al-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (3), respectively. To our best
      knowledge, compound 3 appears to be novel, which was named as wujiapioside A.

PMID- 12510835
TI  - Four new acetylated ginsenosides from processed ginseng (sun ginseng).
AB  - Four new acetylated ginsenosides were isolated from the processed ginseng (SG,
      sun ginseng). Their structures were determined to be 3beta,12beta-dihydroxydammar
      20(22),24-diene-3-O-beta-D-glucopyranosyl(1-->2)-beta-D-6"-O
      acetylglucopyranoside; 3beta,12beta-dihydroxydammar-20(21), 24-diene-3-O-beta-D
      glucopyranosyl(1-->2)-beta-D-6"-O-acetylglucopyranoside; 3beta, 6alpha, 12beta
      trihydroxydammar-20(22),24-diene-beta-O-beta-D-6'-O-acetylglucopyranoside and
      3beta,6a,12beta-trihydroxydammar-20(21),24-diene-6-O-beta-D-6'-O
      acetylglucopyranoside based on spectroscopic evidences. The compounds were named
      ginsenoside Rs4, Rs5, Rs6 and Rs7, respectively.

PMID- 12510836
TI  - Tissue factor inhibitory flavonoids from the fruits of Chaenomeles sinensis.
AB  - Tissue factor (TF, tissue thromboplastin or coagulation factor III) accelerates
      the blood clotting, activating both the intrinsic and the extrinsic pathways to
      serve as a cofactor. In order to isolate TF inhibitors from the fruits of
      Chaenomeles sinensis, an activity-guided purification utilizing a bio-assay
      method of prothrombin time prolongation, was carried out to yield five active
      flavoniods such as hovetrichoside C (1) (IC50 = 14.0 microg), luteolin-7-O-beta-D
      glucuronide (3) (IC50 = 31.9 microg), hyperin (4) (IC50 = 20.8 microg),
      avicularin (6) (IC50 = 54.8 microg) and quercitrin (10) (IC50 = 135.7 microg),
      along with other inactive compounds such as (+/-)-(2E,4E-O-beta-D-glucopyranosyl
      4'-hydroxy-beta-ionylideneacetic acid ester (2), genistein-7-O-beta-D
      glucopyranoside (5), luteolin-3'-methoxy-4'-O-beta-D-glucopyranoside (7),
      luteolin-7-O-beta-D-glucuronide methyl ester (8), tricetin-3'-methoxy-4'-O-beta-D
      glucopyranoside (selagin-4'-O-beta-D-glucopyranoside) (9), (-)-epicatechin (11),
      luteolin-4'-O-beta-D-glucopyranoside (12) and apigenin-7-O-beta-D-glucuronide
      methyl ester (13). The structures of the isolated compounds were elucidated
      through spectral analysis. Among them, compounds 1 to 9,12 and 13 were isolated
      for the first time from the fruits of this plant and the compound 9 is a new
      flavonoid.

PMID- 12510837
TI  - Cytotoxic ergosterols from Paecilomyces sp. J300.
AB  - Seven ergosterol derivatives (1-7) were isolated from silkworm larvae infected
      with Paecilomyces sp. J300. On the basis of spectroscopic means, their structures
      have been elucidated as 3beta,5alpha-dihydroxy-ergosta-7,22-diene (1),
      5alpha,6alpha-epoxy-(22E,24R)-ergosta-8(14), 22-diene-3beta, 7alpha-diol (2),
      5alpha,6alpha-epoxy-(22E,24R)-ergosta-8,22-diene-3beta,7alpha-diol (3), ergosta
      4,6,8(14),22-tetraene-3-one (4), ergosterol (5), ergosterol endoperoxide (6),
      3beta,5alpha-dihydroxy-6beta-methoxyergosta-7,22-diene (7). Compounds 3-7 showed
      moderate cytotoxicity against five tumor cells.

PMID- 12510838
TI  - Acetylcholinesterase inhibitors from the roots of Angelica dahurica.
AB  - In the course of finding Korean natural products for acetylcholinesterase (AChE)
      inhibitory activity, we found that a methanolic extract of the roots of Angelica
      dahurica showed significant inhibitory effects on AChE. Bioassay-guided
      fractionation of the methanolic extract resulted in the isolation of three
      furanocoumarins, isoimperatorin (1), imperatorin (2) and oxypeucedanin (3), as
      active principles. These compounds inhibited AChE activity in a dose-dependent
      manner, and the IC50 values of compounds 1-3 were 74.6, 63.7 and 89.1 microM,
      respectively.

PMID- 12510839
TI  - Antimicrobial activity and chemical composition of some essential oils.
AB  - In this study the composition and antimicrobial properties of essential oils
      obtained from Origanum onites, Mentha piperita, Juniperus exalsa, Chrysanthemum
      indicum, Lavandula hybrida, Rosa damascena, Echinophora tenuifolia, Foeniculum
      vulgare were examined. To evaluate the in vitro antibacterial activities of these
      eight aromatic extracts; their in vitro antimicrobial activities were determined
      by disk diffusion testing, according to the NCCLS criteria. Escherichia coli
      (ATTC 25922), Staphylococcus aureus (ATCC 25923) and Pseudomonas aeruginosa (ATTC
      27853 were used as standard test bacterial strains. Origanum onites recorded
      antimicrobial activity against all test bacteria, and was strongest against
      Staphylococcus aureus. For Rosa damascena, Mentha piperita and Lavandula hybrida
      antimicrobial activity was recorded only to Staphylococcus aureus. Juniperus
      exalsa, and Chrysanthemum indicum exhibited antibacterial activities against both
      Staphylococcus aureus and Escherichia coli. We also examined the in vitro
      antimicrobial activities of some components of the essential oils and found some
      components with antimicrobial activity.

PMID- 12510840
TI  - In vitro antioxidant activity of some selected Prunus species in Korea.
AB  - In the course of the investigations of natural antioxidants, we examined the
      antioxidant activities of the methanol (MeOH) extracts of some selected Prunus
      species, including P buergeriana, P davidiana, P padus, P pendula for. ascendens,
      P. sargentii, P. serrulata var. spontanea and P. yedoensis by three methods as
      represented by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, total ROS
      (reactive oxygen species) and the peroxynitrite (ONOO-) scavenging activity
      tests. We also evaluated the activities of the organic solvent-soluble fractions,
      including the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (n-BuOH)
      fractions and the water (H2O) layer of P serrulata var. spontanea leaves. By
      means of bioassay-directed fractionation, we isolated eleven known flavonoids (1
      11) from the EtOAc soluble fraction of the MeOH extract of the Prunus serrulata
      var. spontanea leaves, exhibiting strong antioxidant activity and characterized
      as prunetin (1), genistein (2), quercetin (3), prunetin 4'-O-beta-glucopyranoside
      (4), kaempferol 3-O-alpha-arabinofuranoside (5), prunetin 5-O-beta
      glucopyranoside (6), kaempferol 3-O-beta-xylopyranoside (7), genistin (8),
      kaempferol 3-O-beta-glucopyranoside (9), quercetin 3-O-beta-glucopyranoside (10)
      and kaempferol 3-O-beta-xylopyranosyl-(1-->2)-beta-glucopyranoside (11).
      Compounds 3 and 10 showed good activities in all tested model systems. Compounds
      2 and 8 showed scavenging activities in the DPPH and ONOO- tests, while compounds
      5, 7, 9 and 11 were active in the ONOO- and ROS tests. On the other hand,
      compounds 1, 4 and 6 did not show any activities in the tested model systems.

PMID- 12510841
TI  - Mechanism of erectogenic effect of the selective phosphodiesterase type 5
      inhibitor, DA-8159.
AB  - DA-8159, a new Phosphodiesterase (PDE) 5 inhibitor, has exhibited potent
      erectogenic potential in a penile erection test in rats and anesthetized dogs. In
      this study, we investigated the mechanism of its erectogenic activity by
      measuring the activity of DA-8159 against a various PDE isozymes and assessing
      cGMP and cAMP formation in a rabbit corpus cavernosum in vitro. DA-8159 inhibited
      the PDE 5 activity in rabbit and human platelets, which the IC50 was 5.84 +/-
      1.70 nM and 8.25 +/- 2.90 nM, respectively. The IC50 of DA-8159 on PDE 1, PDE 2,
      PDE 3 and PDE 6 were 870+/- 57.4 nM, 101 +/- 15 microM, 52.0 +/- 3.53 microM and
      53.3 +/- 2.47 nM, respectively. This suggests that DA-8159 is a potent, highly
      selective, competitive inhibitor of PDE 5-catalyzed cGMP hydrolysis. The rates of
      cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the
      cGMP concentration (5-100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8
      nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA
      8159. DA-8159 increased the apparent Km value for cGMP hydrolysis but had no
      effect on the apparent Vmax, indicating a competitive mode of inhibition. DA-8159
      increased the cGMP concentrations in the rabbit corpus cavernosum dose
      dependently. In the presence of sodium nitroprusside (SNP), DA-8159 significantly
      stimulated the accumulation of cGMP when compared to the control level. This
      indicated that the enhancement of a penile erection by DA-8159 involved the
      relaxation of the cavernosal smooth muscle by NO-stimulated cGMP accumulation. In
      conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis
      and the enhancement of a penile erection by DA-8159 is mediated by the relaxation
      of the cavernosal smooth muscle by the NO-stimulated cGMP accumulation.

PMID- 12510842
TI  - LB30057 inhibits platelet aggregation and vascular relaxation induced by
      thrombin.
AB  - Previous study showed that an amidrazonophenylalanine derivative, LB30057, which
      has high water solubility, inhibited the catalytic activity of thrombin potently
      by interaction with the active site of thrombin. In the current investigation, we
      examined whether LB30057 inhibited platelet aggregation and vascular relaxation
      induced by thrombin. Treatment with LB30057 to platelet-rich plasma (PRP)
      isolated from human blood resulted in a concentration-dependent inhibition of
      thrombin-induced aggregation. Values for IC50 and IC100 were 54 +/- 4 nM and 96
      +/- 3 nM, respectively. This inhibition was agonist (thrombin) specific, since
      IC50 values for collagen and ADP were much greater than those for thrombin. In
      addition, concentration-dependent inhibitory effects were observed on the
      serotonin secretion induced by thrombin in PRP. Consistent with these findings,
      thrombin-induced increase in cytosolic calcium levels was inhibited in a
      concentration-dependent manner. When LB30057 was treated with aortic rings
      isolated from rats, LB30057 resulted in a concentration-dependent inhibition of
      thrombin-induced vascular relaxation. All these results suggest that LB30057 is a
      potent inhibitor of platelet aggregation and blood vessel relaxation induced by
      thrombin.

PMID- 12510843
TI  - Melanogenesis inhibitory activities of diarylheptanoids from Alnus hirsuta Turcz
      in B16 mouse melanoma cell.
AB  - Four diarylheptanoids, (5R-1,7-bis (3,4-dihydroxyphenyl)-heptane-5-O-beta-D
      glucoside (1), (5R) 1,7-bis (3,4-dihydroxyphenyl)-heptane-5-ol (2), oregonin (3),
      hirsutanonol (4), were isolated from the bark of Alnus hirsuta Turcz and its
      inhibitory effects on melanogenesis by measuring the melanin level and tyrosinase
      activity in B16 melanoma cell were examined. Melanin level and tyrosinase
      activity were reduced to 75 to 85% by addition of diarylheptanoids to incubation
      medium of the melanoma cell. On the other hand, melanin level and tyrosinase
      activity were reduced to 13 to 43% by the addition of diarylheptanoids to
      incubation medium of the melanoma cell treated with melanogenesis stimulator,
      alpha-MSH and forskolin. These melanogenesis inhibitory effects were
      significantly different compared with control.

PMID- 12510844
TI  - Pharmacological activities of a new glycosaminoglycan, acharan sulfate isolated
      from the giant African snail Achatina fulica.
AB  - Acharan sulfate (AS) is a glycosaminoglycan (GAG) prepared from the giant African
      snail, Achatina fulica. In this study, some biological activities of AS were
      evaluated on the basis of structural similarities to heparin/heparan sulfate and
      the biological functions of GAGs. We demonstrated that it exhibited strong
      immunostimulating activities as measured by carbon clearance test in mice and in
      vivo phagocytosis. It also exhibited a significant hypoglycemic activity in
      epinephrine (EP)-induced hyperglycemia as well as antifatigue effects by weight
      loaded forced swimming test. And it showed hypolipidemic activities in
      cholesterol-rich mixture induced hyperlipidemia in rats. The above results
      indicate that AS has diverse biological activities and suggest therapeutically
      important target molecules.

PMID- 12510845
TI  - Activation of murine macrophage cell line RAW 264.7 by Korean propolis.
AB  - Monocytes and macrophages play a major role in defense mechanism of the host
      response to tumor, in part through the secretion of several potent products and
      macrophage cytokines. Monocytes and tissue macrophages produce at least two
      groups of protein mediators of inflammation, interleukin 1 (IL-1) and tumor
      necrosis factor (TNF). Recent studies emphasizes that TNF and IL-1 modulate the
      inflammatory function of endothelial cells, leukocytes, and fibroblasts. In this
      study, our work is directed toward studying the in vitro effects of Korean
      propolis on the ability to induce cellular and secretory responses in murine
      macrophage cell line, RAW 264.7. It was found that Water Extract of Korean
      Propolis (WEP) could activate macrophages by producing cytokines. The production
      of the macrophage cytokines, IL-1 and TNF-alpha, by RAW 264.7 treated with WEP
      was examined from 2.5 microg/ml up to 25 microg/ml with dose dependent manner.
      Nitric oxide (NO) production was also increased when cells were exposed to
      combination of LPS and WEP from 2.5 microg/ml up to 25 microg/ml. At high dose of
      WEP (50 to 100 microg/ml) used to prescribe for anti-inflammatory and analgesic
      medicine showed inhibition of NO production in LPS-stimulated macrophage. Besides
      cytokine production, NO release, surface molecule expression and cell morphologic
      antigen expression were increased in response to the stimulation by WEP. These
      results suggested WEP may function through macrophage activation.

PMID- 12510846
TI  - In vitro bioassay for transforming growth factor-beta using XTT method.
AB  - Research in the cytokine field has grown exponentially in recent years, and the
      validity of such studies relies heavily on the appropriate measurement of levels
      of cytokines in various biological samples. Transforming growth factor (TGF)
      beta, a hormonally active polypeptide found in normal and transformed tissue, is
      a potent regulator of cell growth and differentiation. The most widely used
      bioassay for TGF-beta is the inhibition of the proliferation of mink lung
      epithelial cells. Though detection of [3H]thymidine incorporation is more
      sensitive than the MTT assay, it presents some disadvantages due to the safety
      and disposal problems associated with radioisotopes. In this study, we attempted
      to ascertain the experimental conditions which could be used for measuring the in
      vitro biological activity of TGF-beta in a safer and more sensitive way compared
      with the currently available methods. We compared the commonly used method, the
      MTT assay, to the XTT assay using different parameters including cell number,
      incubation time and the wave length used for detecting the product. We examined
      the anti-proliferative activities of TGF-beta in three different cell lines: Mv-1
      Lu mink lung epithelial cells, MCF10A human breast epithelial cells and H-ras
      transformed MCF10A cells. Herein, we present an experimental protocol which
      provides the most sensitive method of quantifying the biological activity of TGF
      beta, with a detection limit of as low as 10 pg/ml: Mv-1-Lu or H-ras MCF10 A
      cells (1 x 10(5)/well) were incubated with TGF-beta at 37 degrees C in a
      humidified CO2 incubator for 24 hr followed by XTT treatment and determination of
      absorbance at 450 or 490 nm. Our results may contribute to the establishment of
      an in vitro bioassay system, which could be used for the satisfactory
      quantitation of TGF-beta.

PMID- 12510847
TI  - Comparative study of the endotoxemia and endotoxin tolerance on the production of
      Th cytokines and macrophage interleukin-6: differential regulation of
      indomethacin.
AB  - Endotoxin tolerance reduces the capacity of monocytes to produce proinflammatory
      cytokines, results in cellular immune paralysis, and down-regulates the
      production of helper T (Th)1 type cytokines with a shift toward a Th2 cytokine
      response. Prostaglandin (PG)E2 in the immune system also results in macrophage
      inactivation and the suppression of Th1 activation and the enhancement of Th2
      activation. However, the inhibitory effects of PGE2 on the altered polarization
      of the Th cell and macrophage interleukin (IL)-6 production characterized in part
      by cellular immune paralysis in a state of endotoxin tolerance is unclear. This
      study was undertaken, using indomethacin, to investigate the role of endogenous
      PGE2 on the Th cytokines and macrophage IL-6 production in a state of endotoxin
      tolerance compared to those with endotoxemia mice, wherein, in this latter case,
      the increased production of proinflammatory cytokines and PGE2 is exhibited.
      Endotoxemia was induced by injection of lipopolysaccharide (LPS; 10 mg/kg in
      saline) ip. once in BALB/c mice, and endotoxin tolerance was induced by
      pretreatment with LPS (1 mg/kg in saline) injected i.p. daily for two consecutive
      days and then with LPS 10 mg/kg on day 4. Splenocytes or macrophages were
      obtained from endotoxemia and endotoxin tolerance models pretreated with
      indomethacin, and then cytokine production was induced by Con A-stimulated
      splenocytes for the Th cytokine assays and LPS-stimulated macrophages for the IL
      6 assay. Our results showed that endotoxemia led to significantly reduced IL-2
      and IL-4 production, to significantly increased IL-6 production, whereas
      interferon (IFN)-gamma production was not affected. Indomethacin in the case of
      endotoxemia markedly attenuated IFN-gamma and IL-6 production and didnt reverse
      IL-2 and IL-4 production. Endotoxin tolerance resulted in the significantly
      reduced production of IL-2 and IFN-gamma and the significantly increased
      production of IL-4 and IL-6. Indomethacin in endotoxin tolerance greatly
      augmented IL-2 production, significantly decreased IL-4 production, and slightly
      attenuated IL-6 production. These findings indicate that endogenous PGE2 may
      mediate the suppressed Th1 type immune response, with a shift toward a Th2
      cytokine response in a state of endotoxin tolerance, whereas endotoxemia may be
      regulated differentially. Also, endogenous PGE2 may mediate macrophage IL-6
      production in the case of endotoxemia to a greater extent than in the case of
      endotoxin tolerance.

PMID- 12510848
TI  - Long-term administration of Sopungsungi-won (SP) prevents diabetic nephropathy in
      Zucker diabetic fatty rats.
AB  - We investigated the long term effects of Sopungsungi-won (SP), a Korean
      traditional formula used for senile constipation and diabetes mellitus, on the
      development of diabetic nephropathy (DN) in Zucker diabetic fatty (ZDF) rats. ZDF
      rats were fed regular laboratory chow mixed with SP or rosiglitazone (RSG) for an
      8-week period. Kidney hypertrophy was developed with increasing plasma glucose
      level, and glomerular hypertrophy was improved by 22% and 45% in SP- and RSG
      treated rats, respectively. Urinary glucose and albumin excretions were also
      significantly lower in SP-treated rats than in ZDF control rats. Activation of
      the mitogen-activated protein kinase (MAPK)-transforming growth factor beta1 (TGF
      beta1)-fibronectin pathway in kidney, responsible for glomerular dysfunction, was
      markedly blunted by SP treatment in a dose dependent manner. Our findings, for
      the first time, provide strong evidence that long-term administration of SP
      formula prevents the development and progression of DN in ZDF rats. Human trials
      are needed to confirm these experimental results.

PMID- 12510849
TI  - Sopungsungi-won (SP) prevents the onset of hyperglycemia and hyperlipidemia in
      Zucker diabetic fatty rats.
AB  - Sopungsungi-won (SP) is a known formula for senile constipation and diabetes
      mellitus, based on traditional Korean medicine. The preventive effect of SP on
      the development of overt diabetes in Zucker diabetic fatty (ZDF) rats was
      evaluated. When administered orally through a diet for 8 weeks, diabetic
      conditions such as hyperglycemia, polydipsia and hypertriglyceridemia were all
      ameliorated in SP-treated rats. In parallel with the onset and progression of
      hyperglycemia in the ZDF control rats; there was a marked decline in plasma
      insulin concentrations from 26.1 microU/ml, at age 7 weeks, to 14.8 microU/ml at
      age 15 weeks. In the SP-treated rats, however, the plasma insulin concentrations
      did not decline, and SP at a dose of 5 g/kg significantly increased the insulin
      levels to 31.9 microU/ml. Early normalization of plasma insulin and a retained
      ability to subsequently increase plasma insulin were indicative of a pancreatic
      beta cell protective action by the SP formula. In addition, expressions of an
      insulin-responsive gene and corresponding protein, glucose transporter 4 (GLUT4),
      in skeletal muscle, were also determined in SP- and rosiglitazone-treated ZDF
      rats. mRNA and protein levels of GLUT4 in SP-treated rats were upregulated in a
      dose dependent manner. Furthermore, when ZDF rats were treated with 2 g/kg of the
      SP formula, the activity of glucose-6-phosphatase was decreased by 49%, whereas
      the activity of glucokinase was increased by 196%, compared to the ZDF control
      rats. Taken together, these data provide evidence that the SP formula markedly
      lowered the plasma glucose levels, probably through an effect not only on
      improvement of insulin action, but through a combined stimulation of glycolysis
      and an inhibition of gluconeogenesis in the liver, and also suggest the validity
      of SP's clinical use in the treatment of type 2 diabetes mellitus following
      further toxicological investigation.

PMID- 12510850
TI  - Influence of cytisine on catecholamine release in isolated perfused rat adrenal
      glands.
AB  - The aim of the present study was to determine the characteristics of cytisine on
      the secretion of catecholamines (CA) in isolated perfused rat adrenal glands, and
      to clarify its mechanism of action. The release of CA evoked by the continuous
      infusion of cytisine (1.5 x 10(-5) M) was time-dependently reduced from 15 min
      following the initiation of cytisine infusion. Furthermore, upon the repeated
      injection of cytisine (5 x 10(-5) M), at 30 min intervals into an adrenal vein,
      the secretion of CA was rapidly decreased following the second injection.
      Tachyphylaxis to the release of CA was observed by the repeated administration of
      cytisine. The cytisine-induced secretion of CA was markedly inhibited by
      pretreatment with chlorisondamine, nicardipine, TMB-8, and the perfusion of Ca2+
      free Krebs solution, while it was not affected by pirenzepine or diphenhydramine.
      Moreover, the secretion of CA evoked by ACh was time-dependently inhibited by the
      prior perfusion of cytisine (5 x 10(-6) M). Taken together, these experimental
      data suggest that cytisine causes secretion of catecholamines from the perfused
      rat adrenal glands in a calcium-dependent fashion through the activation of
      neuronal nicotinic ACh receptors located in adrenomedullary chromaffin cells. It
      also seems that the cytisine-evoked release of catecholamine is not relevant to
      the activation of cholinergic M1-muscarinic or histaminergic receptors.

PMID- 12510851
TI  - Trolox C ameliorates hepatic drug metabolizing dysfunction after
      ischemia/reperfusion.
AB  - The present study was done to determine the effect of trolox C, a hydrophilic
      analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome
      P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats
      were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were
      treated intravenously with trolox C (2.5 mg/kg) or vehide (PBS, pH 7.4), 5 min
      before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels
      were markedly increased after I/R. This increase was significantly suppressed by
      trolox C. Cytochrome P-450 content was decreased after I/R but was restored by
      trolox C. There were no significant differences in ethoxyresorufin O-dealkylase
      (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the
      experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was
      decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R.
      Both these changes were prevented by trolox C. Our findings suggest that trolox C
      reduces hepatocellular damage as indicated by abnormalities in microsomal drug
      metabolizing function during I/R, and that this protection is, in part, caused by
      decreased lipid peroxidation.

PMID- 12510852
TI  - Evaluation of the immune response following exposure of mice to bisphenol A:
      induction of Th1 cytokine and prolactin by BPA exposure in the mouse spleen
      cells.
AB  - Bisphenol A [2, 2 bis (4-hydoxyphenyl) propane; BPA] is a widely used endocrine
      disruptors and has estrogenic activities. Although interests on biological effect
      of BPA are rising, evidences of its effect on immune system are lacking. We
      investigated that the effect of BPA on immune parameters to postulate the
      mechanism, and BPA interruptions between neuroendocrine and immune system. BPA
      was administrated to mice by p.o. (as a drinking water) dose on 0.015, 1.5 and 30
      mg/ml for 4 weeks. The BPA treatment did not result in any change in body weight,
      spleen weight and distribution of lymphocyte subpopulation collected from spleen.
      BPA induced prolactin production in spleen, and exposure of BPA increased the
      activity of splenocyte proliferation in response to Con A (p<0.001). The
      production of a strong Th-1 type cytokine (IFN-gamma) was induced while Th-2 type
      (IL-4) was suppressed by BPA treatment. These were consistent with RT-PCR results
      of transcription factor GATA-3 and IRF-1. These findings suggested that
      stimulation of prolactin production by estrogenic effects of BPA would affect
      cytokine profiles, and lead to imbalanced cellular immune response. In addition,
      we could speculate that prolactin and cytokine is important mediator involved in
      network between neuroendocrine and immune system by BPA.

PMID- 12510853
TI  - Immunoactivation of lectin-conjugated praecoxin A on IL-6, IL-12 expression.
AB  - Lectin-conjugated praecoxin A is a compound, which is combined Wheat Germ
      Agglutinin (WGA) Lectin with praecoxin A and also known to have an anti-tumor
      activity. In our lab, in order to investigate its immune reaction other than the
      anti-tumor activity ever known, we examined cytokines such as IL-6 and IL-12
      through their mRNA expressions, which are generally secreted by macrophage both
      in vivo and in vitro. To analyze, we used RT-PCR for total RNAs of macrophages.
      As a result, we obtained that both in vitro and in vivo, lectin-conjugated
      praecoxin A showed an interesting increase on IL-6 and IL-12 even though it may
      be little hard to say the conjugated form is absolutely more effective than that
      of lectin or praecoxin A alone for immune response activities. Those results
      suggest that the conjugated form may give an additional opportunity in a future
      therapeutic use over its immuno activation properties.

PMID- 12510854
TI  - Colon delivery of prednisolone based on chitosan coated polysaccharide tablets.
AB  - Colon drug delivery is advantageous in the treatment of colonic disease and oral
      delivery of drugs unstable or suceptible to enzymatic degradation in upper GI
      tract. In this study, multilayer coated system that is resistant to gastric and
      small intestinal conditions but can be easily degraded by colonic bacterial
      enzymes was designed to achieve effective colon delivery of prednisolone.
      Variously coated tablets containing prednisolone were fabricated using chitosan
      and cellulose acetate phthalate (CAP) as coating materials. Release aspects of
      prednisolone in simulated gastrointestinal fluid and rat colonic extracts (CERM)
      were investigated. Also, colonic bacterial degradation study of chitosan was
      performed in CERM. From these results, a three layer (CAP/Chitosan/CAP) coated
      system exhibited gastric and small intestinal resistance to the release of
      prednisolone in vitro most effectively. The rapid increase of prednisolone in
      CERM was revealed as due to the degradation of the chitosan membrane by bacterial
      enzymes. The designed system could be used potentially used as a carrier for
      colon delivery of prednisolone by regulating drug release in stomach and the
      small intestine.

PMID- 12510855
TI  - Hepatobiliary excretion of tributylmethylamonium in rats with lipopolysaccharide
      induced acute inflammation.
AB  - The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats
      during acute inflammation (Al) was investigated. Al was induced by an
      intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the
      start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as
      a model OC since it is largely excreted into bile, and is neither metabolized nor
      binds to proteins in the body. When TBuMA was administered intravenously to Al
      rats at a dose of 6.6 micromole/kg, the AUC was increased, while biliary
      excretion (i.e., cumulative amount and apparent clearance) was decreased compared
      to normal rats. When TBuMA was administered intravenously to Al rats at a
      constant rate (i.e., a bolus injection at a dose of 1.5 micromole/kg followed by
      a constant infusion at a rate of 1.5 micromole/kg/hr for 165 min), steady-state
      concentrations of plasma and liver concentrations of TBuMA were increased
      significantly, while in vivo hepatic uptake (amount) and canalicular excretion
      (clearance) were decreased. These results are consistent with a hypothesis in
      which both the sinusoidal uptake of TBuMA into hepatocytes via the OCT1 and the
      canalicular excretion of the compound from hepatocytes via the P-gp are decreased
      by LPS-induced Al.

PMID- 12510856
TI  - Pharmacokinetics of paclitaxel in rabbits with carbon tetrachloride-induced
      hepatic failure.
AB  - The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits
      with carbon tetrachloride-induced hepatic failure. The area under the plasma
      concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased
      in severe carbon tetrachloride-induced hepatic failure rabbits (1,364.54 +/-
      382.07 ng/ml x hr) compared to that of normal rabbits (567.52 +/- 141.88 ng/ml x
      hr), but not significantly in moderate carbon tetrachloride-induced hepatic
      failure rabbits (803.1 +/- 208.81 ng/ml x hr). The volume of distribution (Vd)
      (6.25 +/- 1.56 L) and the elimination rate constant(beta) (0.09 +/- 0.025 hr(-1))
      of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were
      significantly (p<0.05) decreased compared to those of normal rabbits (11.65 +/-
      2.91 L, 0.12 +/- 0.030 hr(-1)), but not significantly in moderate carbon
      tetrachloride-induced hepatic failure rabbits (9.46 +/- 2.37 L, 0.10 +/- 0.026
      hr'). Total body clearance (CLt) of paclitaxel in severe carbon tetrachloride
      induced hepatic failure rabbits (0.733 +/- 0.183 L/hr/kg) was significantly
      (p<0.01) decreased compared to that of normal rabbits (1.762 +/- 0.440 L/hr/kg),
      but not significantly in moderate carbon tetrachloride-induced hepatic failure
      rabbits (1.245 +/- 0.311 L/hr/kg). The half-life(t 1/2) of paclitaxel in severe
      carbon tetrachloride-induced hepatic failure rabbits (7.71 +/- 2.16 hr) was
      significantly (p<0.05) increased compared to that of normal rabbits (5.75 +/-
      1.44 hr), but not significantly in moderate carbon tetrachloride-induced hepatic
      failure rabbits (6.77 +/- 1.76 hr). This results could be due to inhibition of
      paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially
      metabolized in liver. The findings suggest that the dosage regimen of paclitaxel
      should be adjusted when the drug would be administered in patients with liver
      disorder in a clinical situation.

PMID- 12510857
TI  - Small intestinal transit does not adequately represent postoperative paralytic
      ileus in rats.
AB  - Small intestinal transit (SIT) has often been regarded as an index of
      pathophysiological state of postoperative ileus (PI) in rats. The reliability of
      SIT as an index of PI was examined in the present study. PI was induced via
      abdominal surgery (i.e., laparotomy with evisceration and manipulation) in rats.
      For one group of PI-induced rats, SIT of a charcoal test meal was measured. When
      necessary, the physical state (i.e., severity and site of distension) of the
      gastrointestinal (GI) tract in each rat was visually examined. For another group
      of PI-induced rats, abdominal X-ray radiographs were obtained after introducing
      the barium sulfate suspension. The abdomen was then opened and the physical state
      of the GI tract was visually examined. The SIT was decreased in most of the PI
      induced rats, and the GI distension was observed, with substantial intersubject
      variations, in all of the PI-induced rats. However, no linear relationship was
      evident between the SIT and the severity of GI distension (e.g., at 20 h after PI
      induction). Instead, the severity and site of GI distension could be monitored by
      the X-ray radiology. Therefore, the use of SIT as an index of Pi should be
      substantially limited.

PMID- 12510858
TI  - Effect of nitric oxide on the sinusoidal uptake of organic cations and anions by
      isolated hepatocytes.
AB  - The issue of whether or not the presence NOx (NO and oxidized metabolites) in the
      hepatocytes at pathological levels affects the functional activity of transport
      systems within the sinusoidal membrane was investigated. For this purpose, the
      effect of the pretreatment of isolated hepatocytes with sodium nitroprusside
      (SNP), a spontaneous NO donor, on the sinusoidal uptake of tributylmethylammonium
      (TBuMA) and triethylmethyl ammonium (TEMA), representative substrates of the
      organic cation transporter (OCT), and taurocholate, a representative substrate of
      the Na+/taurocholate cotransporting polypeptide (NTCP), was measured. The uptake
      of TBuMA and TEMA was not affected by the pretreatment, as demonstrated by the
      nearly identical kinetic parameters for the uptake (i.e., Vmax, Km and
      CL(linear)). The uptake of mannitol into hepatocytes was not affected,
      demonstrating that the membrane integrity remained constant, irregardless of the
      SNP pretreatment. On the contrary, the uptake of taurocholate was significantly
      inhibited by the pretreatment, resulting in a significant decrease in Vmax, thus
      providing a clear demonstration that NOx preferentially affects the function of
      NTCP rather than OCT on the sinusoidal membrane. A direct interaction between NOx
      and NTCP or a decrease in Na+/K+ ATPase activity as the result of SNP
      pretreatment might be responsible for this selective effect of NOx.

PMID- 12510859
TI  - Fluidising effect of resorcylidene aminoguanidine on sarcolemmal membranes in
      streptozotocin-diabetic rats: blunted adaptation of diabetic myocardium to Ca2+
      overload.
AB  - The "remodelling" of cardiac sarcolemma in diabetes is believed to underlie the
      reduced sensitivity of diabetic hearts due to their overload with extracellular
      calcium. Along with a non-enzymatic glycosylation and the free radical-derived
      glycoxidation of sarcolemmal proteins there is ongoing reduction in cardiomyocyte
      membrane fluidity, the modulator of cardiac sarcolemmal functioning.
      Aminoguanidine derivatives, that inhibit glycation and glycoxidation, might
      suppress myocardium "remodelling" occurring in diabetic heart. To verify this
      hypothesis, we studied physical parameters of cardiac sarcolemma from the
      streptozotocin-induced diabetic rats (45 mg.kg(-1) i.m.) treated with
      resorcylidene aminoguanidine (RAG, 4 or 8 mg.kg(-1) i.m.). The treatment with RAG
      not only completely abolished protein glycation and a generation of free oxygen
      species (p < 0.001) in treated diabetic animals, but also considerably attenuated
      the decrease in sarcolemmal membrane fluidity (p < 0.001). In diabetic animals
      the "normalization" of the sarcolemmal membrane fluidity was accompanied by the
      vastly increased susceptibility of diabetic hearts to be overload with external
      calcium. We concluded that the decreased fluidity of the sarcolemmal membrane,
      apparently linked to the excessive glycation of sarcolemmal membrane proteins,
      might be intimately connected with the adaptation mechanism(s) that are likely to
      develop in diabetic heart to protect it against the overload with external
      calcium.

PMID- 12510860
TI  - Effect of cerebral ventricles perfusion with morphiceptin and Met-enkephalin on
      trigemino-hypoglossal reflex in rats.
AB  - Opioids administered by intracerebroventricular injections produce analgesic
      responses in rats. The present study was undertaken to investigate the effects of
      a highly selective mu-opioid receptor ligand morphiceptin on trigemino
      hypoglossal reflex in rats. The analgesic effect of morphiceptin was compared
      with another opioid peptide, Met-enkephalin. With the experimental settings used
      in this study, we have demonstrated that both morphiceptin and Met-enkephalin
      show significant dose-dependent analgesic effects after i.c.v. administration in
      rats as assayed by trigemino-hypoglossal reflex test. The antinociceptive
      response to Met-enkephalin was short lasting and was observed 10 to 15 min after
      i.c.v. perfusion. Morphiceptin had a relatively longer duration of
      antinociceptive action, the effect was observed 20-50 min after i.c.v. perfusion.
      Neither morphiceptin nor Met-enkephalin produced antinociception after peripheral
      injections. The results of the present study indicate that both tested peptides
      act at mu-opioid receptors situated in the central nervous system. They also
      suggest that mu-opioid receptors present in the central nervous system are an
      important element of the trigemino-hypoglossal reflex arc. For that reason
      selective mu-opioid receptor ligands, like morphiceptin, inhibit the reflex more
      significantly.

PMID- 12510861
TI  - Effects of thapsigargin on stimulation frequency--dependent changes in
      mitochondrial calcium in rat cardiac myocytes.
AB  - We investigated in the single myocytes of rat heart the effect of blocking of ATP
      ase of sarcoplasmic reticulum (SR) on mitochondrial Ca2+ uptake and release.
      Mitochondrial Ca2+ content was investigated as Mn(2+) - resistant fluorescence of
      Indo 1 - AM loaded into cells. SR ATP-ase was blocked with 10(-6) M thapsigargin
      (Tg). Tg blocked almost completely stimulation -dependent mitochondrial Ca2+
      uptake and slowed down its release despite that the maximal cytosolic Ca2+
      concentration was not decreased. We propose that mitochondrial stimulation 
      dependent Ca2+ uptake is greatly enhanced by [Ca2+] built by SR in microdomains
      adjacent to these organelle.

PMID- 12510862
TI  - The role of reactive oxygen species in action of nitric oxide-donors on stress
      induced gastric mucosal lesions.
AB  - The experimental model of acute gastritis such as water immersion restraint (WRS)
      stress-induced gastric injury is useful tool in examination of pathomechanism of
      acute gastritis. Nitric oxide (NO) plays an important role in the maintenance of
      gastric barrier, however, the interaction between reactive oxygen species (ROS)
      and NO on gastric mucosal integrity has been little studied. The purpose of our
      present study was to explain the participation of ROS in healing of WRS-induced
      gastric lesions accelerated by NO. Experiments were carrying out on 120 male
      Wistar rats. To assess gastric blood flow (GBF) laser Doppler flowmeter was used
      and the number of gastric lesions was counted in each stomach. The colorimetric
      assays were used to determine gastric tissue level of malondialdehyde (MDA) and 4
      hydroxynonenal (4-HNE), the products of lipid peroxidation by ROS, as well as
      superoxide dismutase (SOD) activity, the enzyme scavanger of ROS. We demonstrated
      that 3.5 h of WRS resulted in appearance of acute gastric lesions accompanied by
      a significant decrease of GBF. Biological effects of ROS were estimated by
      measuring tissue levels of MDA and 4-HNE, as well as the SOD activity. It was
      demonstrated that 3.5 h of WRS led to significant increase of mucosal levels of
      MDA and 4-HNE, and it was accompanied by a decrease of SOD activity. Pretreatment
      with NO-donors (SIN-1, SNAP, nitroglycerin, NO-ASA) resulted in reduction in
      gastric lesion number, increment of GBF, decrease of MDA and 4-HNE tissue level
      and increase of SOD activity. Suppression of ROS plays an important role in the
      action of NO-donors on healing of acute gastric lesions induced by 3.5 h of WRS.
      NO-donors caused an attenuation of lipid peroxidation as documented by a decrease
      of MDA and 4-HNE levels and enhancement of antioxidative properties as evidenced
      by an increase of SOD activity.

PMID- 12510863
TI  - Influence of leptin administration on the course of acute ischemic pancreatitis.
AB  - Leptin is involved in the regulation of food intake and previous studies have
      shown that leptin affects the inflammatory response in various tissues. The
      objective of this study was to examine the influence of leptin administration on
      the development and the course of acute ischemic pancreatitis. Acute pancreatitis
      was induced by limitation of pancreatic blood flow by clamping of inferior
      splenic artery for 30 min, followed by reperfusion. Leptin was administered three
      times daily at the dose 10 or 50 microg/kg. Animals were sacrificed 1, 3, 5, 10
      and 21 days after removal of vascular clips. Administration of leptin reduced
      development of pancreatic damage and accelerated pancreatic regeneration what was
      manifested by the improvement of pancreatic histology, the decrease in serum
      lipase and amylase activity, and the reduction in serum interleukin-1beta
      concentration. Also, treatment with leptin caused the increase in the pancreatic
      blood flow and pancreatic DNA synthesis. Leptin administration was without effect
      on serum interleukin-10 concentration. Leptin at the dose 50 microg/kg was more
      effective than 10 microg/kg. We conclude that leptin reduces the pancreatic
      damage in the course of ischemic pancreatitis and accelerates the pancreatic
      tissue repair. The beneficial effects of leptin appear to be dependent on the
      improvement of pancreatic blood flow, the increase in pancreatic cell growth, and
      the limitation of pro-inflammatory interleukin-1beta release.

PMID- 12510864
TI  - Role of endogenous melatonin and its MT2 receptor in the modulation of caerulein
      induced pancreatitis in the rat.
AB  - The present study investigated the involvement of endogenous melatonin in the
      prevention of pancreatic damage provoked by caerulein-induced pancreatitis (CIP)
      by using the luzindole, the antagonist of melatonin MT2 receptors. CIP was
      produced by subcutaneous infusion of caerulein to conscious rats (25 microg/kg).
      Luzindole (1, 2 or 4 mg/kg) was given as an intraperitoneal bolus injection 30
      min prior to the start of CIP. Lipid peroxidation products, malondialdehyde (MDA)
      and 4-hydroxynonenal (4-HNE) were measured in the pancreas by LPO-584 commercial
      kit. CIP was confirmed by histological examination and manifested by significant
      increases of plasma activities of amylase, lipase and tumor necrosis factor alpha
      (TNFalpha) (by 500%, 1000% and 600%, respectively) comparing to the control
      values. This was accompanied by a 40% limitation in pancreatic blood flow (PBF)
      and by 200% increase of MDA+4-HNE in the pancreas of CIP rats. Administration of
      luzindole to the CIP rats reduced PBF, aggravated the histological manifestations
      of pancreatitis, resulted in the significant augmentation of pancreatic MDA + 4
      HNE content, and produced the marked increases of plasma levels of lipase,
      amylase and TNFalpha, comparing to the values observes in the rats with CIP
      alone. These results suggest that endogenous melatonin through its receptor MT2
      plays an important role in the attenuation of pancreatic damage produced by
      overstimulation with caerulein.

PMID- 12510865
TI  - MyHC II content in the vastus lateralis m. quadricipitis femoris is positively
      correlated with the magnitude of the non-linear increase in the VO2 / power
      output relationship in humans.
AB  - In this study we have examined the relationship between the content of different
      isoforms of MyHC in the vastus lateralis m. quadricipitis femoris and the VO2 /
      power output relationship during incremental cycling exercise. Twenty-one male
      subjects: aged 24.0 +/- 2.5 years, body mass 73.0 +/- 7.2 kg, height 179 +/- 5
      cm, BMI 22.78 +/- 1.84 kg x m(-2), VO2(max) 3697 +/- 390 ml x min(-1), 50.9 +/-
      5.2 ml x kg(-1) x min(-1), participated in this experiment. The subjects
      performed an incremental exercise test until exhaustion. The exercise test
      started at power output of 30 W, followed by an increase amounting to 30 W every
      3 minutes. The pedalling rate was maintained at 60 rev x min(-1). Gas exchange
      variables were measured continuously using breath-by-breath system Oxycon Jaeger.
      At the end of each step blood samples were taken for lactate concentration.
      Muscle biopsy samples taken from the vastus lateralis m. quadricipitis femoris,
      using the Bergstrom needle, were analysed for the content of different MyHC (I,
      IIa, IIx) using SDS-PAGE and Western blotting. The pre-exercise VO2, as a mean
      value of six-minute measurements, expressed both in ml x min(-1), and in ml x kg(
      1) x min(-1), was positively correlated with the content of MyHC II in the vastus
      lateralis (p < 0.01). We have also found that the pre-exercise values of VO2 in
      the group of subjects with a high proportion of MyHC II (59.9 +/- 11.2 %) were
      significantly higher (p < 0.02, when VO2 was expressed in ml x min(-1), and p <
      0.01 when VO2 was expressed in ml x kg(-1) x min(-1)) than in the group with low
      content of MyHC II (27.5 +/- 6.0 %) in the vastus lateralis. Moreover, we have
      found a significant negative correlation (r = -0.562, p < 0.01) between the slope
      in the VO2/PO relationship below the lactate threshold (LT) and the content of
      MyHC IIa in the vastus lateralis. The most interesting finding of our study was
      that the magnitude of the non-linear increase in the VO2 / power output
      relationship present above the LT was positively correlated ( r = 0.510, p <
      0.02) with the content of MyHC II in the vastus lateralis. Our results show, that
      there is no simple relationship between the content of different types of MyHC in
      the vastus lateralis and the oxygen cost of work during incremental exercise
      test. Individuals with a high content of MyHC II in the vastus lateralis m.
      quadricipitisfemoris consume more oxygen in the pre-exercise conditions than
      subjects with a low content of MyHC II in their muscles. Subjects with a high
      content of MyHC II require a smaller increase in VO2 for maintaining a linear
      increase in power output up to the lactate threshold (lower slope in this
      relationship), but after exceeding the LT, they consume more oxygen above that
      expected from the linear relationship below the LT, than the subjects with a low
      content of MyHC II in their muscles. Therefore, non-linear increase in the VO2 /
      power output relationship, present above the LT, is more pronounced in subjects
      with a higher content of MyHC II in the vastus lateralis m. quadricipitis
      femoris.

PMID- 12510866
TI  - Neurokinin A and the neurohypophysial response to melatonin: in vitro studies.
AB  - The aim of this study was to investigate a possible role of neurokinin A (a
      member of a family of peptides known as tachykinins) in the pineal
      neurohypophysial interrelationship. The effect of neurokinin A (NKA) alone or in
      the presence of pineal hormone - melatonin on basal and K(+)-stimulated
      vasopressin and oxytocin secretion from the hypothalamo-neurohypophysial system
      was studied in vitro. The present results show that NKA stimulated basal
      vasopressin and oxytocin release from the isolated hypothalamo-neurohypophysial
      system, when used at the concentration of 10(-7) M/L. Melatonin diminished basal
      release of the neurohypophysial hormones; it also significantly inhibited the NKA
      stimulated secretion of vasopressin and oxytocin. Lower concentrations of NKA did
      not affect the neurohypophysial hormones basal release, however, when melatonin
      was added to the medium enriched with NKA at the concentration of 10(-9) M/L, the
      vasopressin secretion from the hypothalamo-neurohypophysial explants was
      decreased significantly. The K(+)-evoked release of neurohypophysial hormones was
      not further modified by either NKA or melatonin. The present results confirm
      previous reports as to the inhibitory effect of melatonin on both vasopressin and
      oxytocin secretion from the hypothalamo-neurohypophysial complex in vitro.
      However, under present experimental conditions, the contribution of NKA in the
      mechanisms of pineal-neurohypophysial interrelationships has not been
      demonstrated.

PMID- 12510867
TI  - The role of GABA(A) receptors in the neural systems of the ventromedial
      infundibular region of the hypothalamus in the control of gonadotropin release
      during the luteal phase in ewes.
AB  - To examine the role of GABA(A) receptor mediating systems in the control of
      gonadotropin-releasing hormone (GnRH) release from the ventromedial-infundibular
      region (VEN/NI) in ewes during luteal phase, the extracellular concentrations of
      GnRH, beta-endorphin, noradrenaline (NE), dopamine (DA), and their metabolites:
      MHPG and DOPAC were quantified by local stimulation or blockade of GABA(A)
      receptors with muscimol or bicuculline, respectively. Stimulation of GABA(A)
      receptors in the VEN/NI did not affect GnRH, beta-endorphin release or
      catecholaminergic system activity. Blockade of GABA(A) receptors decreased beta
      endorphinergic and dopaminergic activity, and lowered the extracellular
      concentration of MHPG. It did not affect GnRH release or luteinizing hormone (LH)
      secretion. It is suggested that progesterone-induced GABAergic activity during
      the luteal phase may desensitize GABA(A) receptors to muscimol. Lack of changes
      in GnRH/LH secretion with concomitant depressed beta-endorphinergic activity
      corroborated the conclusion that beta-endorphin does not inhibit GnRH release
      from the VEN/NI during the luteal phase. The physiological significance of
      changes in the catecholaminergic system activity under GABA(A) receptor blockade
      in the control of GnRH secretion awaits to be established.

PMID- 12510868
TI  - Involvement of prostaglandins in the nicotine-induced pituitary-adrenocortical
      response during social stress.
AB  - The present study examined the functional selectivity of nicotine for nicotinic
      acetylcholine receptors in the stimulation of the hypothalamic-pituitary-adrenal
      (HPA) axis, the effect of social crowding stress on HPA response to nicotine and
      the involvement of prostaglandins synthesized by constitutive cyclooxygenase (COX
      1) and inducible cyclooxygenase (COX-2) in the nicotine-induced HPA response in
      rats crowded (24 per a box instead 7) for 7 days. Nicotine (2.5-5.0 mg/kg i.p.)
      significantly increased plasma ACTH and corticosterone levels measured 1 h after
      administration. Mecamylamine (50 mg i.c.v.), a selective nicotinic receptor
      antagonist, atropine (0.1 mg/kg i.p.) a non-selective cholinergic receptor
      antagonist, or COX inhibitors were injected 15 min prior to nicotine and the rats
      were decapitated 1 h after the last injection. Mecamylamine abolished the
      nicotine-induced ACTH response and significantly diminished corticosterone
      response. Atropine did not alter ACTH response and modestly diminished
      corticosterone response to nicotine. Crowding stress significantly impaired the
      nicotine-evoked ACTH and corticosterone secretion. Pretreatment with piroxicam
      (0.2-2.0 mg/kg), a COX-1 inhibitor, considerably diminished the nicotine-induced
      ACTH and corticosterone secretion in control and crowded rats. Compound NS-398
      (0.2-5.0 mg/kg), a selective COX-2 blocker, did not markedly alter the nicotine
      induced hormones secretion in either control or stressed rats. Indomethacin (2
      mg/kg), a non-selective COX inhibitor diminished significantly, but to a lesser
      extent than piroxicam, the nicotine-stimulated ACTH and corticosterone response.
      These results indicate that systemic nicotine stimulates the HPA axis selectively
      via nicotinic acetylcholine receptors. Chronic social stress significantly
      impairs the nicotine stimulated ACTH and corticosterone secretion.
      Prostaglandins, generated by COX-1- but not by COX-2- isoenzyme, are of crucial
      significance in the nicotine-induced ACTH and corticosterone secretion in both
      control and stressed rats.

PMID- 12510869
TI  - Influence of several convulsants on the protective activity of a non-competitive
      AMPA/kainate antagonist, LY 300164, and lamotrigine against maximal electroshock
      in mice.
AB  - Aminophylline (50-100 mg/kg) and strychnine (0.125-0.5 mg/kg) significantly
      raised the ED50 values of LY 300164 against maximal electroshock in mice, from 4
      to 8 mg/kg (aminophylline 100 mg/kg) and from 3.6 to 11.5 mg/kg (strychnine 0.5
      mg/kg). Also, aminophylline (25-50 mg/kg) and strychnine (0.125-0.25 mg/kg)
      increased the ED50 value of lamotrigine in this test, for instance from 5.5 to
      8.0 mg/kg (aminophylline 50 mg/kg) and from 5.2 to 8.9 mg/kg (strychnine 0.25
      mg/kg). Moreover, the ED50S values of aminophylline and strychnine for the
      reduction of the anticonvulsant effect of LY 300164 (7 mg/kg, the dose equal to
      its ED97 value against maximal electroshock) were 79.9 and 0.2 mg/kg,
      respectively. The respective ED50 values for the inhibition of the antiseizure
      action of lamotrigine were 40.9 and 0.2 mg/kg. Neither bicuculline nor picrotoxin
      affected the protective action of LY 300164 or lamotrigine. Strychnine
      significantly lowered the plasma concentrations of LY 300164 and this my point to
      a pharmacokinetic mechanism of the observed interaction. Aminophylline did not
      affect the plasma concentrations of the studied anticonvulsant drugs and
      strychnine - that of lamotrigine, so a pharmacokinetic interaction does not seem
      probable. The present results indicate that the potential of aminophylline and
      strychnine to attenuate the anticonvulsant activity of conventional
      antiepileptics is extended to LY 300164 and lamotrigine.

PMID- 12510870
TI  - Distribution of endogenous retinoids, retinoid binding proteins (RBP, CRABPI) and
      nuclear retinoid X receptor beta (RXRbeta) in the porcine embryo.
AB  - Retinoids are important signalling molecules in the development of limbs and in
      the determination of the anterior-posterior orientation of the embryo. The
      present study examined the content and distribution of retinoic acid, retinol and
      retinyl esters in porcine embryos during early gestation (gestation days 22-30)
      macroscopically and microscopically by its autofluorescence and by HPLC.
      Macroscopically, the yellowish-greenish autofluorescence characteristic of
      vitamin A was observed in tissues affected by morphogenesis, such as the limbs,
      in a spatial and temporal manner. Changes in the intensity of autofluorescence in
      the limbs paralleled changes in the concentration of retinoids in these
      structures. In the limbs and the body, retinol, retinyl palmitate, and all-trans
      retinoic acid but neither the isomers of all-trans retinoic acid nor other
      retinoid metabolites were detected. In addition, the distribution of specific
      retinoid-binding proteins was investigated; these are involved in vitamin A
      transport, metabolism and signal transduction. Immunoreactive retinol-binding
      protein as well as cellular retinoic acid binding protein type I were only
      localised in the mesonephros, while the retinoid X receptor beta was widely
      distributed in most of the tissues and organs of the embryo throughout the time
      period investigated. The combination of autofluorescence and HPLC analysis
      allowed for the first time to attribute the yellowish-greenish autofluorescence
      in specific regions of the embryo to vitamin A, and offers a method to study the
      local cellular distribution of retinol and/or retinyl esters as well as their
      concentrations in embryonic tissues.

PMID- 12510871
TI  - Influence of the load of nylon capsules on their passage through the digestive
      tract and specific gravity.
AB  - The passage and specific gravity of nylon capsules were evaluated in five trials.
      In individual trials, different lactating cows were fed the same diet consisting
      of maize silage, alfalfa hay and concentrate. In each trial the different feeds
      (or no feed) were used to fill the capsules. The capsules were made of nylon
      cloth (42 microm pore size, 10 mm external diameter). The different weights of
      the load (L1-L5) were obtained using a combination of 2 and 3 mm stainless steel
      balls. The highest recovery of the capsules was obtained with the L3 and L4 loads
      (91.4 and 92.3%, resp.). After 14 hours of incubation in the rumen, the
      calculated values of functional specific gravity of the capsules ranged from 0.92
      to 2.05 g x cm(-3). It was concluded that L3 (one 2 mm and one 3 mm ball) was the
      suitable weight of the load.

PMID- 12510872
TI  - Influence of lipoic acid on lipid metabolism and beta-adrenergic response to
      intravenous or oral administration of clenbuterol in broiler chickens.
AB  - The effects of lipoic acid (LA) on muscle growth, metabolic response and hepatic
      respiration in broilers treated with or without clenbuterol (CLE) were examined.
      In 4-week-old chickens, dietary LA administration (100 mg x kg(-1)) enhanced the
      beta-adrenergic response of plasma nonesterified fatty acid with an intravenous
      injection of CLE (50 microg x kg(-1), estimated from the response area for 120
      min (-7,860 vs. 874 micromol x L(-1) min in control and LA-treated groups,
      respectively; P < 0.05). When chickens received long-term oral administration of
      CLE (0.25 mg x kg(-1)) for 30 d, LA interfered with the repartitioning action of
      CLE, decreased abdominal fat weight (P < 0.05) and increased protein
      concentration of the breast muscle (P < 0.05), in 7-week-old chickens. In
      addition, the LA supplementation alone increased both plasma nonesterified fatty
      acid (P < 0.05) and triacylglycerol (P < 0.05), whereas these effects were not
      associated with CLE administration. These findings suggest that the dietary LA
      level used stimulates rapid lipolytic response of plasma nonesterified fatty acid
      to CLE injection and fatty acid turnover between adipose tissue and the liver,
      but does not facilitate the repartitioning action of CLE during long-term
      treatment in broilers.

PMID- 12510873
TI  - Neural differentiation of mouse embryonic stem cells grown in monolayer.
AB  - To drive neural differentiation of mouse embryonic stem (ES) cells, various
      culture protocols have been previously developed that all require the formation
      of embryoid bodies, usually combined with a treatment by all-trans retinoic acid
      (aRA). Here, we investigated whether or not neural differentiation can also occur
      in a simplified monolayer culture. Mouse ES cells were plated in serum-containing
      DMEM media with and without aRA and grown under these conditions for 2 days.
      Then, the cells were transferred to fresh serum-containing DMEM media and/or to
      serum-free DMEM/F12 media supplemented with a mixture of insulin, transferrin,
      selenium, and fibronectin (ITSF) for further culture. The changes in cell
      morphology and in the expression of selected molecular markers were monitored.
      Generally, in contrast to all the others, the protocol consisting of a 2-day
      culture in serum-containing DMEM followed by continuous exposure to the ITSF
      supplement in DMEM/F12 drove a vast majority of ES cells to generate phenotypic
      signs of neural lineage. Altogether, neural differentiation can be achieved in
      vitro without the step involving the formation of embryoid bodies as well as the
      treatment by aRA.

PMID- 12510874
TI  - The influence of estradiol and progesterone on the concentrations of uterine
      oxytocin receptors and plasma PGFM in response to oxytocin in ovariectomized
      gilts.
AB  - Peripubertal gilts (n = 25) were treated with corn oil (CO) or ovarian steroids,
      one month following an ovariectomy. The first day of treatment was assigned as
      the first day of the experiment. The gilts received: Group (Gr) I (n = 4)--CO (2
      mL x day(-1) from 1st to 12th day), Gr II (n = 4) and Gr III (n = 4)-
      progesterone (P4; 10 to 100 mg x day(-1) from 1st to 12th day), Gr IV (n = 5)-
      estradiol benzoate (EB; 400 microg x day(-1) from 1st to 3rd day), Gr V (n = 4)
      and Gr VI (n = 4)--EB + P4 (EB 400 microg x day(-1) from 1st to 3rd day, 20
      microg x day(-1) at 6th and 9th day, 50 microg at 12th day plus P4 10 to 100 mg
      from 4th to 15th day). All gilts were injected with oxytocin (OT; 20 IU; i.v.) on
      the following days of the experiment: 13th (Gr I and Gr II), 15th (Gr III and Gr
      IV), 16th (Gr V) and 18th (Gr VI). Concentrations of the PGF2alpha metabolite-
      PGFM were determined in blood samples, collected from 30 min before to 120 min
      after OT injection. Baseline PGFM concentrations (30 min before OT) differed
      among treatment groups and were the highest in Gr V and Gr VI (P < 0.01 vs. other
      groups). The magnitude of the PGFM response to OT increased only in four of the
      five gilts of Gr IV and in three of the four gilts of Gr VI, and it was higher (P
      = 0.009) in Gr VI than in Gr IV. In the remaining groups, PGFM concentrations did
      not increase above the baseline in response to OT. The day after OT injection,
      oxytocin receptors (OTR) were found in the uterine tissues of all animals
      studied. The lowest OTR concentrations were in Gr I--75.5 +/- 11.2 fmol x mg
      protein(-1) and the highest in Gr IV--712.9 +/- 86.7 fmol x mg protein(-1); (P <
      0.05 vs. other groups). The values of K of OTR differed among groups (P < 0.001)
      and ranged from 1.62 +/- 0.44 nM in Gr I to 12. 08 +/- 1.9 nM in Gr VI. A
      positive correlation (r = 0.54; P < 0.01) between plasma E2 and uterine OTR
      concentrations was observed. In conclusion, E2 and P4 are involved in both PGF2
      synthesis/secretion and OTR formation, however, full PGF response to OT does not
      develop before puberty. Estrogens are evident stimulators of uterine OTR
      synthesis ingilts.

PMID- 12510875
TI  - Small intestine growth and morphometry in piglets weaned at 7 days of age.
      effects of level of energy intake.
AB  - Two trials involving a total of 56 pigs were conducted to examine the effects of
      weaning at 7 d of age (trial 1) and of energy intake level and length of post
      weaning underfeeding period (trial 2) on small intestinal (SI) development and
      morphometry. At 3 d after weaning, weight of the SI and mucosa (g/kg body weight)
      and villous height along SI were reduced by 20, 36 and 41%, respectively,
      compared to the day of weaning. Intestinal morphometrical changes are dependent
      on SI site and days post-weaning. Villous atrophy on d 3 and recovery on d 14
      post-weaning were greater and occurred earlier in the proximal than in the medial
      and distal SI. Villous height was dependent on the level of energy intake which
      explains 56% of the variations in proximal SI villous height in weaned pigs and
      73% when data of the sow-reared pigs were included in the analysis. Moreover,
      after 4 d of refeeding, underfed piglets showed similar villous characteristics
      to piglets fed a continuously high feeding level after weaning stressing that
      capacities of intestinal restoration were not affected by the length of the post
      weaning underfeeding period. Overall, the present results suggest a spatial and
      temporal effect of weaning on villous atrophy and recovery, and that the level of
      energy intake is a major factor accounting for the post-weaning villous height.

PMID- 12510876
TI  - Regulation of IGF-I and porcine oviductal secretory protein (pOSP) secretion into
      the pig oviduct in the peri-ovulatory period, and effects of previous nutrition.
AB  - The mechanisms regulating oviduct function were investigated. In Experiment 1,
      porcine oviductal secretory protein (pOSP) mRNA, and pOSP and insulin-like growth
      factor (IGF-I) in oviductal flushings, decreased through the peri-ovulatory
      period. In Experiment 2, higher plasma steroids in oviductal veins, ipsilateral
      (INT), rather than contralateral (OVX), to the remaining ovary in unilaterally
      ovariectomized gilts, were associated with higher pOSP in INT oviductal
      flushings. In Experiment 3, oviduct function was assessed as part of a
      collaborative study in cyclic gilts. Feed restriction in the late, compared to
      the early, luteal phase reduced estradiol concentrations in oviductal plasma,
      pOSP mRNA in oviductal tissue, and IGF-I concentrations and pOSP abundance in
      oviduct flushings. Previous insulin treatment differentially affected oviduct
      function. These data provide the first direct evidence for effects of previous
      feed restriction and insulin treatment on the oviduct environment in the peri
      ovulatory period, which may contribute to nutritional effects on embryonic
      survival.

PMID- 12510877
TI  - Effect of calf suckling on oxytocin, prolactin, growth hormone and milk yield in
      crossbred Gir x Holstein cows during milking.
AB  - This study evaluated the effect of different milking managements on oxytocin,
      prolactin and growth hormone release in Gir x Holstein cows. Six cows were
      suckled by their calves, before and after milking (SM group); another six cows
      were submitted to exclusive milking (M group). High OT levels were observed
      during suckling of the SM group, however both groups had similar levels of OT
      during milking. The SM group presented PRL levels significantly higher than the M
      group, however only during suckling. For GH levels, the SM group showed higher
      levels than the M group, however this difference was significant only during the
      first suckling, cleaning of the teats and at the beginning of machine milking.
      Despite these results, SM cows produced more milk (milking plus suckling) than M
      cows, however milk obtained by milking was similar for both groups.

PMID- 12510878
TI  - Plasma levels of cortisol and oxytocin, and uterine activity after cervical
      artificial insemination in the ewe.
AB  - The objective was to compare in the ewe the effects of easy and difficult
      procedures for artificial insemination (AI) (as related to rapid or poor
      accessibility of the cervix, respectively) on plasma cortisol (CORT) and oxytocin
      (OT), and uterine motility. All AI were simulated using a catheter empty of semen
      to study genital and environmental stimuli only. In experiment 1, 40 ewes were
      sampled after Al, and whether it was an easy or difficult procedure was reported
      for each animal. While CORT concentrations rose to a similar amount in all ewes,
      whatever the Al procedure, a significant OT response occurred after a difficult
      procedure only (n = 18) (17.4 +/- 1.7 versus 12.7 +/- 0.7 pg x mL(-1) before Al,
      p < 0.05). In experiment 2, uterine activity was monitored in 4 ewes using an
      implantable telemetric transmitter equipped with an intrauterine pressure
      catheter. An increased uterine activity occurred during 2 +/- 1 min after an easy
      Al (n = 5), whereas the evoked activity lasted for 15 +/- 4 min after a difficult
      Al (p < 0.001, n = 7). A similar long-lasting response occurred after OT
      administration (100 mIU, i.v.). We concluded that the increase in uterine
      motility after a difficult Al resulted from a reflex release of OT, and not to a
      "stress" effect.

PMID- 12510879
TI  - Discriminant and quantitative PLS analysis of competitive CYP2C9 inhibitors
      versus non-inhibitors using alignment independent GRIND descriptors.
AB  - This study describes the use of alignment-independent descriptors for obtaining
      qualitative and quantitative predictions of the competitive inhibition of CYP2C9
      on a serie of highly structurally diverse compounds. This was accomplished by
      calculating alignment independent descriptors in ALMOND. These GRid INdependent
      Descriptors (GRIND) represent the most important GRID-interactions as a function
      of the distance instead of the actual position of each grid-point. The
      experimental data was determined under uniform conditions. The inhibitor data set
      consists of 35 structurally diverse competitive stereospecific inhibitors of the
      cytochrome P450 2C9 and the non -inhibitor data set of 46 compounds. In a PLS
      discriminant analysis 21 inhibitors and 21 non-inhibitors (1 and 0 as activities)
      were analyzed using the ALMOND program obtaining a model with an r2 of 0.74 and a
      cross-validation value (q2) of 0.64. The model was externally validated with 39
      compounds (14 inhibitors/25 non-inhibitors). 74% of the compounds were correctly
      predicted and an additional 13% was assigned to a borderline cluster. Thereafter,
      a model for quantitative predictions was generated by a PLS analysis of the GRIND
      descriptors using the experimental Ki-value for 21 of the competitive inhibitors
      (r2 = 0.77, q2 = 0.60). The model was externally validated using 12 compounds and
      predicted 11 out of 12 of the Ki-values within 0.5 log units. The discriminant
      model will be useful in screening for CYP2C9 inhibitors from large compound
      collections. The 3D-QSAR model will be used during lead optimization to avoid
      chemistry that result in inhibition of CYP2C9.

PMID- 12510880
TI  - A validation study on the practical use of automated de novo design.
AB  - The de novo design program Skelgen has been used to design inhibitor structures
      for four targets of pharmaceutical interest. The designed structures are compared
      to modeled binding modes of known inhibitors (i) visually and (ii) by means of a
      novel similarity measure considering the size and spatial proximity of the
      maximum common substructure of two small molecules. It is shown that the Skelgen
      algorithm generates representatives of many inhibitor classes within a very short
      time and that the new similarity measure is useful for comparing and clustering
      designed structures. The results demonstrate the necessity of properly defining
      search constraints in practical applications of de novo design.

PMID- 12510881
TI  - De novo ligand design with explicit water molecules: an application to bacterial
      neuraminidase.
AB  - Most computer-aided drug design methods ignore the presence of
      crystallographically-determined water molecules in the binding site of a target
      protein. In this paper, our de novo ligand design methods are applied to the X
      ray crystal structure of bacterial neuraminidase in the presence of some selected
      water molecules. We have found that, for this particular protein, the complete
      removal of all bound water molecules leads to difficulties in generating any
      potential ligands if the unsatisfied hydrogen-bonding sitepoints left by removing
      these water molecules are to be satisfied by a ligand. As more of the
      crystallographically determined water molecules are allowed in the binding site,
      it becomes much easier to generate ligands in larger numbers and with wider
      chemical diversity. This example shows that, in some cases, bound water molecules
      can be more accessible for hydrogen bonding to an incoming ligand than the actual
      protein binding sitepoints associated with them. From the point of view of de
      novo ligand design, water molecules can thus act as versatile amphiprotic
      hydrogen-bonding sitepoints and reduce the conformational constraints of a
      particular binding site.

PMID- 12510882
TI  - Theoretical descriptors for the quantitative rationalisation of plastocyanin
      mutant functional propertiess.
AB  - A quantitative rationalisation of the effect of specific amino acids on the
      recognition process and redox characteristics of plastocyanin towards cytochrome
      f, as determined by point mutation experiments, has been attempted in this study.
      To achieve this goal we derived theoretical descriptors directly from the three
      dimensional structure of the plastocyanin mutants, in the same manner as it is
      usually done for small drug-like molecules. The protein descriptors computed can
      be related to: (a) the electrostatic and dipole-dipole interactions, effective at
      long distance; (b) polar interactions whose features are encoded by charged
      partial surface area descriptors; (c) the propensity of the surface residues to
      form hydrogen bonding interactions; and (d) dispersion and repulsive
      interactions. Moreover, an estimation of mutation-dependent variation of redox
      potential observed has been obtained by electrostatic free energy calculations.
      The quantitative structure-activity relationship (QSAR) models offer structural
      interpretation of the point mutation experiment responses and can be of help in
      the design of new protein engineering experiments.

PMID- 12510883
TI  - A homology-based model of the human 5-HT2A receptor derived from an in silico
      activated G-protein coupled receptor.
AB  - A homology-based model of the 5-HT2A receptor was produced utilizing an activated
      form of the bovine rhodopsin (Rh) crystal structure. In silico activation of the
      Rh structure was accomplished by isomerization of the 11-cis-retinal (1)
      chromophore, followed by constrained molecular dynamics to relax the resultant
      high energy structure. The activated form of Rh was then used as a structural
      template for development of a human 5-HT2A receptor model. Both the 5-HT2A
      receptor and Rh are members of the G-protein coupled receptor (GPCR) super
      family. The resulting homology model of the receptor was then used for docking
      studies of compounds representing a cross-section of structural classes that
      activate the 5-HT2A receptor, including ergolines, tryptamines, and amphetamines.
      The ligand/receptor complexes that ensued were refined and the final binding
      orientations were observed to be compatible with much of the data acquired
      through both diversified ligand design and site directed mutagenesis.

PMID- 12510884
TI  - Maximum common subgraph isomorphism algorithms for the matching of chemical
      structures.
AB  - The maximum common subgraph (MCS) problem has become increasingly important in
      those aspects of chemoinformatics that involve the matching of 2D or 3D chemical
      structures. This paper provides a classification and a review of the many MCS
      algorithms, both exact and approximate, that have been described in the
      literature, and makes recommendations regarding their applicability to typical
      chemoinformatics tasks.

PMID- 12510885
TI  - Development and validation of a simulation model for blowfly strike of sheep.
AB  - A comprehensive simulation model for sheep blowfly strike due to Lucilia sericata
      (Meigen) (Diptera: Calliphoridae), which builds on previously published versions
      but also incorporates important new empirical data, is used to explain patterns
      of lamb and ewe strike recorded on 370 farms in south-west, south-east and
      central England and Wales. The model is able to explain a significant percentage
      of the variance in lamb strike incidence in all four regions, and ewe strike in
      three of the four regions. The model is able to predict the start of seasonal
      blowfly strike within one week in three of the four regions for both ewes and
      lambs, and within 3 weeks in the fourth region. It is concluded that the accuracy
      of the model will allow it to be used to assess the likely efficacy of new
      control techniques and the effects of changes in existing husbandry practices on
      strike incidence. The model could also be used to give sheep farmers advance
      warning of approaching strike problems. However, the ability to forecast future
      strike patterns is dependent on the accuracy of the weather projections; the more
      long-term the forecast, the more approximate the prediction is likely to be. When
      applied on a regional basis, model forecasts indicate expected average patterns
      of strike incidence and may not therefore be appropriate for individual farmers
      whose husbandry practices differ substantially from the average.

PMID- 12510886
TI  - Stream-bank shade and larval distribution of the Philippine malaria vector
      Anopheles flavirostris.
AB  - The principal malaria vector in the Philippines, Anopheles flavirostris (Ludlow)
      (Diptera: Culicidae), is regarded as 'shade-loving' for its breeding sites, i.e.
      larval habitats. This long-standing belief, based on circumstantial observations
      rather than ecological analysis, has guided larval control methods such as
      'stream-clearing' or the removal of riparian vegetation, to reduce the local
      abundance of An. flavirostris. We measured the distribution and abundance of An.
      flavirostris larvae in relation to canopy vegetation cover along a stream in
      Quezon Province, the Philippines. Estimates of canopy openness and light
      measurements were obtained by an approximation method that used simplified
      assumptions about the sun, and by hemispherical photographs analysed using the
      program HEMIPHOT. The location of larvae, shade and other landscape features was
      incorporated into a geographical information system (GIS) analysis. Early larval
      instars of An. flavirostris were found to be clustered and more often present in
      shadier sites, whereas abundance was higher in sunnier sites. For later instars,
      distribution was more evenly dispersed and only weakly related to shade. The best
      predictor of late-instar larvae was the density of early instars. Distribution
      and abundance of larvae were related over time (24 days). This pattern indicates
      favoured areas for oviposition and adult emergence, and may be predictable.
      Canopy measurements by the approximation method correlated better with larval
      abundance than hemispherical photography, being economical and practical for
      field use. Whereas shade or shade-related factors apparently have effects on
      larval distribution of An. flavirostris, they do not explain it completely. Until
      more is known about the bionomics of this vector and the efficacy and
      environmental effects of stream-clearing, we recommend caution in the use of this
      larval control method.

PMID- 12510887
TI  - Domestic scorpion control with pyrethroid insecticides in Mexico.
AB  - Scorpion stings cause more morbidity in Mexico than any other country, leading to
      about 100 deaths annually. In 1999, the State of Morelos reported nine deaths
      among 30663 cases of scorpion sting. To replace lindane used for scorpion
      control, field trials of pyrethroid pesticides were undertaken in Morelos during
      1998-2000 at the village of Chalcatzingo (population initially with 2760
      inhabitants and 530 houses). Pre-intervention surveys detected scorpions
      (Scorpiones: Buthidae) of two species in the majority of houses: Centruroides
      limpidus limpidus Karsch outnumbering Vaejovis mexicanus smithi Koch. Scorpion
      prevalence was assessed, pre- and post-spray, directly by searching (40
      min/house) and by householder reports of sightings inside houses. Pre
      intervention perceptions of scorpion abundance were similar for all areas, with
      sightings in 12-18% of houses, whereas daytime searches detected more
      infestations in eastern parts of the village (prevalence 17% indoors, 22%
      outdoors) than in other sectors (9% indoors, 14% outdoors). Pyrethroids were
      evaluated as residual treatments in separate sectors of Chalcatzingo, with almost
      complete coverage indoors and peridomestically, using the following four
      formulations: bifenthrin 10% wettable powder (WP) applied at 50mg a.i./m2,
      cyfluthrin 10% WP (Solfac 10 WP) at 44-55 mg a.i./m2, deltamethrin 2.5%
      suspension concentrate (Biothrin 25 SC) at 11 mg a.i./m2 and 5% WP (K-Othrine 50
      WP) at 35 mg a.i./m2. Phase 1 compared bifenthrin 10 WP, Solfac 10 WP and
      Biothrin 25 SC sprayed in December 1998; phase 2 compared Solfac 10 WP and K
      Othrine 50 WP sprayed in June and again in December 2000, with follow-up surveys
      of scorpions one month post-spray and subsequently. Scorpion prevalence was
      reduced by 64-77% peridomestically one month post-spray and by 83, 46 and 15% in
      houses sprayed with cyfluthrin WP, bifenthrin WP or deltamethrin SC,
      respectively. Householder reports of sighting scorpions indoors were 33-85% below
      pre-intervention levels. Cumulative effects of the three spray-rounds over 3
      years reduced scorpion prevalence by approximately 60% in the deltamethrin WP re
      sprayed area and by approximately 90% in the cyfluthrin WP re-sprayed area.
      Householder sightings also fell by 67 and 28% in the cyfluthrin and delta-methrin
      re-sprayed areas, respectively. Operational efficacy of these products against
      scorpions at the dosages applied was ranked as cyfluthrin WP > bifenthrin WP >
      deltamethrin SC > WP. Reported cases of scorpion sting intoxication fell by 17%
      during this study after having risen by approximately 40% over four previous
      years.

PMID- 12510888
TI  - Spatial pattern of abundance of the mosquito, Ochlerotatus albifasciatus, in
      relation to habitat characteristics.
AB  - Ochlerotatus albifasciatus (Macquart) (Diptera: Culicidae) is the main vector of
      the western equine encephalomyelitis (WEE) virus and potentially of other
      arboviruses in Argentina. Surges of adult population abundance during the rainy
      season are a nuisance, affecting milk and beef production. Larvae develop in
      short periods in shallow temporary ground pools on fresh or brackish water.
      Although adults seem to disperse long distances from larval habitats, little is
      known about their habitat preferences. This work studied factors affecting the
      spatial pattern of adult Oc. albifasciatus abundance. Adult mosquitoes were
      collected using CDC miniature light traps baited with CO2 at 28 sites located to
      the south of Mar Chiquita Lagoon, from November 1997 to April 1998. Each site was
      typified according to its predominating vegetation cover, potential breeding site
      occurrence, land slope and cattle density. The spatial and temporal patterns of
      abundance suggested that Oc. albifasciatus prefers prairies and natural
      grasslands subject to periodic flooding vs. woodland and farm land. A
      discriminant function based on the proximity to potential larval habitats,
      distance to woodland and land slope accurately classified 95% of the data
      categorized as having an average high (>500 mosquitoes) or low (<500 mosquitoes)
      abundance, and was validated using six sites located away from the study area. An
      analysis of the temporal variation of mosquito abundance highlighted the
      influence of the dynamics of the larval habitats on adult mosquito abundance.

PMID- 12510889
TI  - A comparison of the vector competence of the biting midges, Culicoides (Avaritia)
      bolitinos and C. (A.) imicola, for the Bryanston serotype of equine encephalosis
      virus.
AB  - Equine encephalosis virus (EEV) is widespread and prevalent in southern Africa.
      In this study, the oral susceptibility of Culicoides (Avaritia) imicola Kieffer
      (Diptera: Ceratopogonidae) to EEV was confirmed. In addition, C. (A.) bolitinos
      Meiswinkel, collected in the high-lying eastern Free State, South Africa, was
      systemically infected with the Bryanston serotype of EEV after feeding through a
      membrane on artificially infected equine blood containing 4.7 log10 PFU/mL of
      EEV. The mean infectivity of Bryanston virus in C. bolitinos increased from 1.2
      log10 PFU/midge, in midges assayed for virus immediately after feeding on the
      blood-virus mixture, to 3.1 log10 PFU/midge in midges assayed after 10 days'
      incubation at 23.5 degrees C. Elevated virus infectivity titres, found in
      individual infected C. bolitinos, suggested that this Culicoides species is a
      vector of EEV. This bovine dung-breeding Culicoides species may play an important
      role in transmitting EEV in the cooler parts of southern Africa, where it can be
      the most abundant Culicoides species collected near livestock. In the present
      study the prevalence of infection obtained for C. bolitinos (2.2%) with the
      Bryanston serotype of EEV was significantly lower than that of C. imicola
      (18.4%). After incubation, the Bryanston serotype of EEV was also isolated from
      one of 110 C. onderstepoortensis Fiedler assayed. However, the virus titre in
      this midge was 1.2 log10 PFU/midge, which is not different from the titre that
      would be expected immediately after feeding on the blood-virus mixture.
      Culicoides species that survived the incubation period and that were negative for
      the presence of Bryanston virus were C. magnus Colaco (96), C. bedfordi Ingram &
      Macfie (95) and C. pycnostictus Ingram & Macfie (45).

PMID- 12510890
TI  - Structure and function of the gnathosoma of the mange mite, Psoroptes ovis.
AB  - Mites of the genus Psoroptes (Acari: Psoroptidae) are obligate, non-burrowing,
      astigmatid ectoparasites of mammals. A detailed understanding of the morphology
      of the gnathosoma is an important step towards elucidation of the feeding
      behaviour of this mite and, hence, the pathology of psoroptic mange. Scanning and
      transmission electron microscopy were used to examine Psoroptes ovis (Hering)
      (syn. P. cuniculi). The gnathosoma is composed of an infracapitulum (hypostome),
      which forms the floor of an extended U-shaped pre-oral trough, bounded by
      laterally compressed palps and enclosing paired chelicerae. Distally, each palp
      terminates in a flap-like process and four tapered terminal sensillae. The floor
      of the infracapitulum is interrupted along its length by a dorsally projecting
      ridge. At the distal end of the infracapitulum are paired, grooved pseudorutellae
      and, between them, paired, ungrooved lateral lips. Between the lateral lips is a
      grooved, elongate labium. Medially, a pair of finger-like projections emanates
      from the paraxial walls of the palps and project anteriorly. Each chelicera is
      made up of fixed and mobile digits, with a cheliceral membranous fold
      articulating the two. The distal ends of both digits are chelated. For much of
      its length, the mobile cheliceral digit appears to lie within a fold formed by
      the infracapitular ridge, thereby creating a central channel between the
      chelicerae. It is suggested that this arrangement of elements may facilitate a
      two-way flow of liquid, where saliva flows down a central salivary canal and
      spills out onto the host's skin over the labium at the point where the chelated
      tips of the chelicerae meet and abrade the skin. Liquid food may move along the
      grooves of the pseudorutellae and then be sucked up a food canal formed by the
      paraxial walls of the palps and the outer wall of the chelicerae.

PMID- 12510891
TI  - Completion of the sequence of the nuclear ribosomal DNA subunit of Simulium
      sanctipauli, with descriptions of the 18S, 28S genes and the IGS.
AB  - We describe the IGS-ETS, 18S and 28S ribosomal gene sequences of Simulium
      sanctipauli Vajime & Dunbar, a member of the S. damnosum Theobald (Diptera:
      Simuliidae) complex of blackflies (Diptera: Simuliidae). These regions, together
      with the ITS-1, ITS-2 and 5.8S rDNA presented elsewhere (accession number
      U36206), constitute the composite sequence of the entire rDNA unit, making S.
      sanctipauli the second dipteran species of medical importance for which the
      entire rDNA has been sequenced. Despite the lack of sequence identity, the IGS of
      S. sanctipauli showed some structural similarities to other Diptera, i.e. the
      mosquito Aedes albopictus Skuse (Culicidae), the fruitfly Drosophila melanogaster
      Meigen (Drosophilidae) and the tsetse Glossina (Glossinidae). Two blocks of
      tandemly repeated subunits were present in the IGS of S. sanctipauli and, unlike
      other species of Diptera, they contained no duplications of promoter-like
      sequences. However, two promoter-like sequences were identified in the unique DNA
      stretches of the IGS by their sequence similarity to the promoter of Aedes
      aegypti L. (Diptera: Culicidae). The observed sequence variation can be
      explained, as in the case of Drosophila spp., by the occurrence of slippage-like
      and point mutation processes, with unequal crossing-over homogenizing (to a
      certain extent) the region throughout the gene family and blackfly population.
      The 18S and 28S rDNA genes show more intraspecific variability within the
      expansion segments than in the core regions. This is also the case in the
      interspecific comparison of these genes from S. sanctipauli with those of
      Simulium vittatum, Ae. albopictus and D. melanogaster. This pattern is typical of
      many eukaryotes and likely to be the result of a more relaxed functional
      selection in the expansion segments than on the core regions. The A + T content
      of the S. sanctipauli genes is high and similar to those of other Diptera. This
      could be the result of a change in the mutation pressure towards AT in the
      Diptera lineage.

PMID- 12510892
TI  - Assessment of rDNA IGS as a molecular marker in the Simulium damnosum complex.
AB  - For five cytospecies of the Simulium damnosum Theobald complex of blackflies
      (Diptera: Simuliidae) from West Africa, both ends of the intergenic spacer region
      (IGS) of the rDNA have been sequenced with the aim of developing specific
      molecular markers. No specific differences in these two regions were detected
      between Simulium sanctipauli V. & D., Simulium sirbanum V. & D., Simulium
      soubrense V. & D., Simulium squamosum Enderlein and Simulium yahense V. & D.,
      except in the number of A subrepeats at the 5' end of the IGS (two in S.
      squamosum and four or five in the others) and in position 310 of the 3' end (a C
      in S. squamosum and a G in the others). However, genetic distances within and
      between species overlapped. These DNA sequences had no strong phylogenetic
      signal, and the trees obtained were mostly unresolved. Although most sequences
      from S. squamosum clustered together, a few of them were more similar to those in
      other cytospecies. These results could be explained either by hybridization with
      genetic introgression or by ancestral polymorphism and recent speciation.

PMID- 12510893
TI  - Insecticide-treated plastic tarpaulins for control of malaria vectors in refugee
      camps.
AB  - Spraying of canvas tents with residual pyrethroid insecticide is an established
      method of malaria vector control in tented refugee camps. In recent years,
      plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian
      shelter material for displaced populations in complex emergencies. Advances in
      technology enable polythene sheeting to be impregnated with pyrethroid during
      manufacture. The efficacy of such material against mosquitoes when erected as
      shelters under typical refugee camp conditions is unknown. Tests were undertaken
      with free-flying mosquitoes on entomological study platforms in an Afghan refugee
      camp to compare the insecticidal efficacy of plastic tarpaulin sprayed with
      deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin impregnated
      with deltamethrin (initially > or = 30 mg/m2) during manufacture, and a tent made
      from the factory impregnated tarpaulin material. Preliminary tests done in the
      laboratory with Anopheles stephensi Liston (Diptera: Culicidae) showed that 1-min
      exposure to factory-impregnated tarpaulins would give 100% mortality even after
      outdoor weathering in a temperate climate for 12 weeks. Outdoor platform tests
      with the erected materials (baited with human subjects) produced mosquito
      mortality rates between 86-100% for sprayed or factory-impregnated tarpaulins and
      tents (average approximately 40 anophelines and approximately 200 culicines/per
      platform/night), whereas control mortality (with untreated tarpaulin) was no more
      than 5%. Fewer than 20% of mosquitoes blood-fed on human subjects under either
      insecticide-treated or non-treated shelters. The tarpaulin shelter was a poor
      barrier to host-seeking mosquitoes and treatment with insecticide did not reduce
      the proportion blood-feeding. Even so, the deployment of insecticide-impregnated
      tarpaulins in refugee camps, if used by the majority of refugees, has the
      potential to control malaria by killing high proportions of mosquitoes and so
      reducing the average life expectancy of vectors (greatly reducing vectorial
      capacity), rather than by directly protecting refugees from mosquito bites. Mass
      coverage with deltamethrin-sprayed or impregnated tarpaulins or tents has strong
      potential for preventing malaria in displaced populations affected by conflict.

PMID- 12510894
TI  - Transmission dynamics of lymphatic filariasis: density-dependence in the uptake
      of Wuchereria bancrofti microfilariae by vector mosquitoes.
AB  - Gaining a better understanding of parasite infection dynamics in the vector
      mosquito (Diptera: Culicidae) population is central to improving knowledge
      regarding the transmission, persistence and hence control of lymphatic
      filariasis. Here, we use data on mosquito feeding experiments collated from the
      published literature to examine the available evidence regarding the functional
      form of the first component of this parasite-vector relationship for Wuchereria
      bancrofti (Filarioidea: Onchocercidae) causing Bancroftian filariasis, i.e. the
      rate of microfilariae (mf) uptake from the blood of infected humans by the
      feeding mosquito vector. Using a simple logarithmic regression model for
      describing the observed relationships between the mean numbers of mf ingested per
      mosquito and parasite load in humans in each study, and a linear mixed-effects
      meta-analytical framework for synthesizing the observed regressions across
      studies, we show here for the first time clear evidence for the existence of
      density-dependence in this process for all the three major filariasis
      transmitting mosquito vectors. An important finding of this study is that this
      regulation of mf uptake also varies significantly between the vector genera,
      being weakest in Culex, comparatively stronger in Aedes and most severe and
      occurring at significantly lower human mf loads in Anopheles mosquitoes. The
      analysis of the corresponding mf uptake prevalence data has further highlighted
      how density-dependence in mf uptake may influence the observed distributions of
      mf in vector populations. These results show that whereas strong regulation of mf
      uptake, especially when it leads to saturation in uptake at low human parasite
      intensities, can lead to static distributions of mf per mosquito with host
      parasite intensity, a weaker regulation of mf ingestion can give rise to changes
      in both mean mf loads and in the frequency distribution of parasites/mosquito
      with increasing human parasite intensity. These findings highlight the importance
      of considering local vector infection dynamics when attempting to predict the
      impacts of community-based filariasis control. They also emphasize the value of
      developing and applying robust meta-analytic methods for estimating functional
      relationships regarding parasitic infection from population ecological data.

PMID- 12510895
TI  - Isoenzyme variation in Aedes aegypti correlated with Dirofilaria immitis
      infectability.
AB  - From the Vero Beach strain of the mosquito Aedes (Stegomyia) aegypti (L.)
      (Diptera: Culicidae), substrains were selected for susceptibility (SS) and
      refractoriness (RR) to the dog heartworm Dirofilaria immitis (Leidy)
      (Filarioidea: Onchocercidae). These two lines and their reciprocal F1 hybrids
      were analysed for genetic variation at 14 enzyme loci, using polyacrylamide gel
      electrophoresis. Six of the enzyme loci showed variation (sample size 48
      alleles/locus/line). Three of these were monomorphic in the refractory line but
      polymorphic in the susceptible, i.e. aconitase hydratase (Acoh), isocitrate
      dehydrogenase-1 (Idh-1) and phosphoglucomutase (Pgm). The other three loci,
      glucose-6-phosphate isomerase (Gpi), hexokinase-1 (Hk-1) and isocitrate
      dehydrogenase-2 (Idh-2), were polymorphic in both SS and RR lines and their
      hybrids. At two loci (Hk-1, Pgm) three alleles were detected, whereas the other
      polymorphic loci had only two alleles. For Hk-1, the most frequent allele was Hk
      1(80) (0.563) in refractory and Hk-1(100) in the susceptible (0.521) and F1
      hybrids. For Pgm the most frequent alleles were Pgm125 in the susceptible line
      (0.646) and Pgm100 in the F1 hybrids (0.563 and 0.604) and refractory line
      (1.000). The mean observed heterozygosity (Ho), the mean Hardy-Weinberg expected
      heterozygosity (He) and the mean number of alleles per locus in the refractory
      line were lower, but not significantly so, than in the susceptible line and their
      reciprocal F1 hybrids; the proportion of polymorphic loci was significantly lower
      in the refractory than in the susceptible line and their F1 hybrids. Within both
      lines all polymorphisms were in Hardy-Weinberg equilibrium, whereas significant
      departures from predicted frequencies were observed in SS x RR hybrids at four
      polymorphic loci (Acoh, Gpi, Hk-1, Pgm) and at three polymorphic loci (Acoh, Hk
      1, Pgm) in RR x SS hybrids. The average Nei's and modified Rogers' genetic
      distances between the lines were 0.024 and 0.139, respectively. These
      electrophoretic data show that the refractory line (putatively lacking fi allele)
      can be distinguished from the susceptible line (fi/fi) and their hybrids
      (heterozygous fi) by isozyme marker frequencies, but it remains to be seen
      whether this difference is causal or chance linkage. In any case, this model
      system of Ae. aegypti/D. immitis provides opportunities to better understand and
      manipulate the molecular biology of filariasis transmission.

PMID- 12510896
TI  - Distribution and phenology of ixodid ticks in southern Zambia.
AB  - Distribution data for epidemiologically important ticks (Acari: Ixodidae) in the
      Southern Province of Zambia, one of the main cattle areas of the country, are
      presented. Boophilus microplus (Canestrini) was not recorded in southern Zambia,
      whereas Boophilus decoloratus (Koch) is present throughout the area. New
      distribution patterns for less economically important ixodid ticks are also
      discussed. Southern Zambia is a transition zone because it is the most northern
      area in Africa where mixed Rhipicephalus appendiculatus Neumann and Rhipicephalus
      zambeziensis Walker, Norval & Corwin populations were reported. Although a second
      generation of adult R. appendiculatus/R. zamnbeziensis was encountered,
      simulations indicated that this phenomenon is very rare in southern Zambia,
      mainly because of the colder temperatures during the early dry season and lower
      rainfall. These simulations were supported by a development trial under
      experimental conditions. Tick body size measurements showed that southern Zambian
      ticks are larger than eastern Zambian R. appendiculatus. It is hypothesized that
      body size is related to diapausing intensity in this species. The epidemiological
      consequences are that a different approach to control Theileria parva (Theiler)
      (Piroplasmida: Theileriidae) and other tick-borne diseases is needed in southern
      Zambia, compared to the one adopted in eastern Zambia.

PMID- 12510897
TI  - Dermatitis in humans associated with the mites Pyemotes tritici, Dermanyssus
      gallinae, Ornithonyssus bacoti and Androlaelaps casalis in Israel.
AB  - Multiple erythematous papules accompanied by severe pruritus were observed in
      humans bitten by the mites (Acari) Pyemotes tritici (Newport) (Pyemotidae),
      Dermanyssus gallinae (De Geer) (Dermanyssidae), Ornithonyssus bacoti Hirst
      (Macronyssidae) and Androlaelaps casalis (Berlese) (Laelapidae). Eight case
      histories are presented and the impact of these species on human health is
      discussed.

PMID- 12510898
TI  - Consumption of flea faeces and eggs by larvae of the cat flea, Ctenocephalides
      felis.
AB  - The effects of the consumption of flea faeces and non-viable eggs on larval
      development in the cat flea Ctenocephalides felis (Bouche) (Siphonaptera:
      Pulicidae) were investigated. Only 13.3% of larvae developed into adults when fed
      a diet of male or female flea faeces alone; however, 90% of larvae developed into
      adults when fed on flea faeces supplemented with non-viable flea eggs. When fed
      with non-viable eggs alone, larvae did not develop into adults. Nevertheless, non
      viable eggs may provide critical supplemental nutrients, lacking in flea faeces
      and required for larval development. None of the larvae fed on flea faeces or non
      viable eggs alone formed a cocoon. A diet of flea faeces alone significantly
      extended the second as well as third larval stadia compared to larvae fed on
      diets containing non-viable eggs. It is suggested that the cannibalism of fertile
      eggs may limit population growth in the cat flea.

PMID- 12510899
TI  - Pyrethroid resistance in tropical bedbugs, Cimex hemipterus, associated with use
      of treated bednets.
AB  - When Tanzanian villages were provided with pyrethroid-treated bednets, bedbugs
      (Cimicidae) disappeared; however, after about 6 years they have re-appeared in
      these villages. Using a newly devised test-kit, susceptibility tests of bedbugs
      Cimex hemipterus (Fabricius) from five of these villages showed that there is
      resistance to permethrin and alphacypermethrin in bedbugs from each of the
      villages, in contrast to those from five villages without treated nets.
      Circumstantial evidence indicates that bedbug resistance to pyrethroid
      insecticides may evolve more readily in villages with incomplete coverage rates
      of treated bednets, allowing bedbug infestations to become re-established.
      Bedbugs have not returned to a village where nearly all the beds have been
      provided with pyrethroid-treated bednets for 14 years.

PMID- 12510900
TI  - In situ hybridization to the Rdl locus on polytene chromosome 3L of Anopheles
      stephensi.
AB  - We are interested in generating a Y-autosome translocation of the Resistance to
      dieldrin (Rdl) locus in the malaria vector mosquito Anopheles stephensi Liston
      (Diptera: Culicidae), for use in sterile insect release. To ensure stability of
      the system, a recombination suppressing inversion can also be induced which
      encompasses the Rdl locus. As a first step, here we report the cloning of
      fragments of the Rdl gene from both An. stephensi and An. gambiae Giles using
      degenerate primers in the polymerase chain reaction. These fragments encode the
      second membrane-spanning region of the gamma-aminobutyric acid receptor and show
      high levels of both nucleotide and predicted amino acid identity to other Rdl
      like receptors. They confirm that, as in all other arthropod species examined,
      dieldrin resistance in An. stephensi is associated with replacement of
      alanine302, in this case with a serine. In situ hybridization of the Rdl probe to
      polytene chromosomes of An. stephensi localizes the gene to the left arm of
      chromosome 3 (3L) in region 45C. Rdl localization will enable us to identify
      chromosomal rearrangements encompassing the Rdl locus and help anchor the genome
      sequence of An. gambiae to the polytene map.

PMID- 12510901
TI  - Isoenzyme differentiation of Aedes aegypti populations in French Guiana.
AB  - Population genetics of peri-domestic Aedes aegypti (Diptera: Culicidae), vector
      of dengue and yellow fever, were investigated by gel electrophoresis of 10 enzyme
      loci in 14 samples of mosquito larvae collected in 1997-1998 from localities
      separated by distances of 3-275 km in French Guiana. Genetic differentiation
      between geographical populations was generally high (mean FST = +0.111, P < 10(
      5)) even among seven sites <30 km apart (FST = +0.137, P < 0.05), but not
      positively correlated with distance. Thus, Ae. aegypti comprises a mosaic of
      genetically differentiated populations in French Guiana. This may be attributed
      to reinvasion from diverse origins through repeated founder events after this
      vector species was eliminated during the 1940s to 1960s.

PMID- 12510902
TI  - Simultaneous identification of species and molecular forms of the Anopheles
      gambiae complex by PCR-RFLP.
AB  - For differential identification of sibling species in the Anopheles gambiae Giles
      complex (Diptera: Culicidae), including simultaneous separation of M and S
      molecular forms within An. gambiae Giles sensu stricto, we describe a PCR-RFLP
      method. This procedure is more efficient, faster and cheaper than those used
      before, so is recommended for large-scale processing of field-collected larval
      and adult specimens to be identified in malaria vector studies.

PMID- 12510903
TI  - Long QT syndrome and anaesthesia.
AB  - The long QT syndrome is a disorder of myocardial electrical conduction that
      leaves the heart vulnerable to the ventricular tachydysrhythmia torsade de
      pointes. Clinically, this results in syncope or sudden death. The long QT
      syndrome may be congenital, if caused by abnormal myocardial potassium or sodium
      ion channels, or acquired, if due to drugs, electrolyte abnormalities or
      metabolic conditions. Triggers for the development of torsade de pointes include
      both anaesthesia and surgery. Some anaesthetic agents prolong the QT interval.
      The condition is reviewed and suggestions are made for the anaesthetic management
      of affected patients.

PMID- 12510904
TI  - Oxygen transport and myocardial function after the administration of albumin 5%,
      hydroxyethylstarch 6% and succinylated gelatine 4% to rabbits.
AB  - BACKGROUND AND OBJECTIVE: The effects of administering albumin 5%,
      hydroxyethylstarch 6% and succinylated gelatine 4% on oxygen transport and left
      ventricular function were prospectively investigated in different experimental
      conditions: baseline, fluid load, after 10 min of myocardial ischaemia and after
      reperfusion. METHODS: Twenty-seven rabbits received at random one of three
      colloids in escalating boluses over 10-15 min to achieve left ventricular end
      diastolic pressures (LVEDP) between 8 and 10mmHg. A branch of the left anterior
      descending coronary artery was then temporarily occluded by a ligature and
      released after 10 min. Myocardial function was assessed using left ventricular
      pressure recordings and dimension data obtained from ultrasound crystals inserted
      onto the ventricular wall. Blood was sampled for the determination of oxygen
      delivery and consumption, the oxygen extraction ratio, acid-base status, and
      glucose and lactate concentrations. RESULTS: Administration of the colloids
      similarly increased oxygen delivery and improved left ventricular function in all
      groups. Peak rate of pressure development (dP/dt(max)) and oxygen delivery were
      reduced during ischaemia and reperfusion. The decrease in dP/dt(max) was more
      pronounced in the hydroxyethylstarch group. CONCLUSIONS: Administration of
      albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% had similar
      effects on oxygen delivery and myocardial function. After ischaemia and during
      reperfusion, the decrease in myocardial function was most pronounced with
      hydroxyethylstarch 6%.

PMID- 12510905
TI  - Preload and haemodynamic assessment during liver transplantation: a comparison
      between the pulmonary artery catheter and transpulmonary indicator dilution
      techniques.
AB  - BACKGROUND AND OBJECTIVE: Liver transplantation is characterized by several
      changes in intravascular blood volume due to vasodilatation based on neurohumoral
      mediators, intraoperative bleeding and anaesthesia technique effects. Today, with
      the transpulmonary indicator dilution technique, cardiac index (CIart) can be
      evaluated and preload assessed in terms of the intrathoracic blood volume index
      (ITBVI). The aim was to analyse in patients undergoing liver transplantation two
      preload variables, pulmonary artery occlusion pressure (PAOP) and ITBVI with
      respect to cardiac index (CIpa) and stroke volume index (SVIpa), the correlation
      between ITBVI and PAOP, and secondary the relationship between the changes
      (delta) of ITBVI and PAOP and the changes of CIpa and SVIpa, and the
      relationships between deltaITBVI and deltaPAOP. The reproducibility and precision
      of all CIart and CIpa measurements were also evaluated. METHODS: A prospective
      study was performed in 60 patients monitored with a pulmonary artery catheter and
      with the PiCCO system. The variables were evaluated with a linear regression
      model. RESULTS: Linear regression analysis between ITBVI-CIpa and ITBVI-SVIpa
      were r2 = 0.47 (P < 0.0001) and r2 = 0.55 (P < 0.0001) respectively, while PAOP
      poorly correlated to CIpa (r2 = 0.02), SVIpa (r2 = 0.015) and ITBVI (r2 = 0.002).
      Only changes in ITBVI were correlated with changes in CIpa (delta1, r2 = 0.37;
      delta2, r2 = 0.32), and SVIpa (delta1, r2 = 0.60; delta2, r2 = 0.47). The mean
      bias between CIart and CIpa was 0.13 L min(-1) m(-2) (2 SD = 1.04L min(-1) m(-2))
      (r2 = 0.86, P < 0.0001). CONCLUSIONS: In comparison with PAOP, ITBVI seems a more
      reliable indicator of cardiac preload in patients undergoing liver
      transplantation.

PMID- 12510906
TI  - Haemodynamic and splanchnic organ blood-flow responses to hypotension induced by
      the calcitonin gene-related peptide and sodium nitroprusside in dogs.
AB  - BACKGROUND AND OBJECTIVE: To elucidate the effects of various degrees of
      hypotension induced by the calcitonin gene-related peptide (CGRP) on the
      splanchnic circulation, we investigated the renal and hepatic blood flow during
      hypotension induced by either the calcitonin gene-related peptide or sodium
      nitroprusside in the isoflurane-anaesthetized dog. METHODS: Anaesthesia was
      maintained with 1.3% isoflurane in oxygen. After the baseline period, mean
      arterial pressure was reduced to 60 mmHg in the CGRP60 and nitroprusside groups,
      and to 50 mmHg in the CGRP50 group. The splanchnic organ blood flow was measured
      by hydrogen clearance. RESULTS: The cardiac index in the CGRP60 group increased
      (P < 0.01), but in the CGRP50 group it decreased (P < 0.01), and in the
      nitroprusside group it remained unchanged during hypotension. Mean pulmonary
      artery and pulmonary capillary wedge pressures in the CGRP60 group remained
      unchanged, but in the CGRP50 and nitroprusside groups they decreased (P < 0.01)
      during hypotension. Cardiac contractility in the CGRP60 group remained unchanged,
      whereas in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) during
      hypotension. Renal blood flow in the CGRP60 group was relatively well maintained
      but in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) throughout
      the observation. Hepatic blood flow in all three groups was reduced (P < 0.01)
      during hypotension. The reductions in hepatic blood flow between the Calcitonin
      gene-related peptide groups were associated with a dose-dependent decrease in
      mean arterial pressure. CONCLUSIONS: The results suggest that calcitonin gene
      related peptide acts as an arteriolar vasodilator at low doses but as a
      vasodilator of the arteriolar and venous systems at higher doses, and that
      profound hypotension induced by the calcitonin gene-related peptide may impair
      splanchnic circulation.

PMID- 12510907
TI  - Neuromuscular effects of rapacuronium on the diaphragm and skeletal muscles in
      anaesthetized patients using cervical magnetic stimulation for stimulating the
      phrenic nerves.
AB  - BACKGROUND AND OBJECTIVE: Non-depolarizing neuromuscular blocking agents have a
      shorter duration of action on the diaphragm than on skeletal muscles. It was to
      be tested if this also held true for rapacuronium, a short-acting, amidosteroid
      non-depolarizing neuromuscular blocker, lately withdrawn from the market, using a
      novel technique for stimulating the diaphragm and assessing its function.
      METHODS: Anaesthesia was induced with propofol 2 mg kg(-1) and remifentanil 1
      microg kg(-1), and the trachea was intubated after topical anaesthesia.
      Rapacuronium was given at a dose of 1.5 mg kg(-1). The diaphragm was stimulated
      by cervical magnetic stimulation of the phrenic nerves (2 Tesla, single coil) and
      airway pressure responses were measured at the endotracheal tube connector. The
      neuromuscular effects at the adductor pollicis and orbicularis oculi muscles were
      measured by acceleromyography. RESULTS: Fifteen males and five females (ASA I and
      II; 27 +/- 8 yr; 73 +/- 13kg; mean +/- SD) were recruited. Median maximal
      relaxation was less (P < 0.01) for the diaphragm (89%) than for the adductor
      pollicis or orbicularis oculi muscles (each 100%). The time to 25% recovery was
      shorter for the diaphragm than for adductor pollicis or orbicularis oculi (7.5 +/
      3.1 versus 14.1 +/- 3.7 and 15.1 +/- 3.5 min, respectively, P < 0.01). Recovery
      from 25 to 75% was identical for the diaphragm and adductor pollicis (9.4 +/- 2.9
      versus 9.1 +/- 3.5 min), but longer for orbicularis oculi (13.4 +/- 4.2 min, P <
      0.01). The median recovery time to TOF0.8 was shorter for the diaphragm (23.9
      min) than for the adductor pollicis or orbicularis oculi muscles (31.5 and 28.4
      min, respectively; P < 0.05). CONCLUSIONS: As with other non-depolarizing muscle
      relaxants, the duration of the clinical effect of rapacuronium was shorter for
      the diaphragm than for skeletal muscle. The recovery index was identical for the
      diaphragm and adductor pollicis.

PMID- 12510908
TI  - Fate of abstracts from the Paris 1995 European Society of Anaesthesiologists
      meeting.
AB  - BACKGROUND AND OBJECTIVE: To assess the publication rate of full papers presented
      as abstracts at the 1995 meeting of the European Society of Anaesthesiologists,
      and to assess factors that might predict subsequent full publication. METHODS:
      All abstracts presented at the meeting and published in the British Journal of
      Anaesthesia (Suppl 1, 1995) were included. To verify subsequent full publication,
      a MEDLINE search was performed and validated. We studied the average time from
      the meeting to publication, the first author's country, the subspeciality, the
      publishing journal of the full report, the type of presentation (oral or poster),
      the object of investigation, and the quality of research design and of
      statistical reporting in the abstract. RESULTS: Of 472 meeting abstracts, 199
      (42.2%) were eventually published. The average (+/- SD) delay between meeting and
      publication was 16.8 (15.6) months (range 24-60 months). Most papers (79.4%) had
      been published within 3 yr of the meeting. Circulation, pharmacology and
      intensive care papers had the highest rates of publication. Sixty-three journals
      attracted papers, with the British Journal of Anaesthesia publishing most (n =
      29). No difference in subsequent publication was found between oral and poster
      presentations. Randomized trials and animal research were more likely to be
      published. The number of authors or their positions differed between the abstract
      and the full publication in 145 cases (72.9%); the first author was changed in 43
      cases. CONCLUSIONS: Less than half of the abstracts accepted at the 1995 European
      Society of Anesthesiologists' meeting were subsequently published in journals
      indexed by MEDLINE in the 3 yr following the meeting. Many changes in authorship
      occurred between the abstract and the full publication. The study architecture
      and the object of investigation predicted full publication.

PMID- 12510909
TI  - Is traditional fasting policy changing? Results of a Swiss survey on current
      practice.

PMID- 12510910
TI  - General anaesthesia for a child with Rubinstein-Taybi syndrome.

PMID- 12510911
TI  - Anaesthesia for open-heart surgery in a patient with Weaver's syndrome.

PMID- 12510912
TI  - Effects of thiamylal, sevoflurane and isoflurane on the cortically recorded
      somatosensory evoked potentials.

PMID- 12510913
TI  - Evaluation of phase-shifting approaches for a point-diffraction interferometer
      with the mutual coherence function.
AB  - The estimation accuracy of a point-diffraction interferometer is examined with
      two phase-shifting schemes: spatial and temporal. Under the assumption of plane-
      or spherical-wave propagation through isotropic turbulence that can be accurately
      represented as a series of thin phase screens, results that are valid for any
      scintillation regime are obtained by use of the invariance with a propagation of
      the mutual coherence function. It is established that the estimation accuracy of
      the spatial phase-shifting point-diffraction interferometer is invariant with
      scintillation. Upper and lower bounds on the perfor mance of the temporal phase
      shifting point-diffraction interferometer are developed. Wave optical simulation
      results are presented that validate the analytic predictions for the two phase
      shifting schemes. The results and techniques presented can be used to assess the
      appropriate phase-shifting scheme given finite resources, such as a limited
      number of pixels in a detector array or a restricted detector frame rate.

PMID- 12510914
TI  - Effectiveness of simultaneous independent realizations at low carrier-to-noise
      ratio to improve heterodyne Doppler lidar performance. I. Experimental results.
AB  - A 1.55-microm continuous-wave heterodyne Doppler lidar (HDL) with three receiver
      detector units is used to validate experimentally the findings presented in the
      Guerit et al. companion paper [Appl. Opt. 41, 2232 (2002)] on the effectiveness
      of independent realizations to improve HDL performance (velocity or power
      estimates or both) at a low carrier-to-noise ratio (CNR). In fact, noise has a
      detrimental effect on the accumulation techniques, so in the Guerit et al.
      companion paper, the chances of getting "heavy" speckles in HDL signal from many
      receiver-detector units on a single- or several-shot basis are investigated
      theoretically and numerically with the Zrnic HDL model. The experimental results
      enable us to conclude there is a very good agreement (better than 95%) between
      the performance computed from actual HDL data and from the theoretical
      prediction.

PMID- 12510915
TI  - Spatial filtering efficiency of monostatic biaxial lidar: analysis and
      applications.
AB  - Results of lidar modeling based on spatial-angular filtering efficiency criteria
      are presented. Their analysis shows that the low spatial-angular filtering
      efficiency of traditional visible and near-infrared systems is an important cause
      of low signal/background-radiation ratio (SBR) at the photodetector input The low
      SBR may be responsible for considerable measurement errors and ensuing the low
      accuracy of the retrieval of atmospheric optical parameters. As shown, the most
      effective protection against sky background radiation for groundbased biaxial
      lidars is the modifying of their angular field according to a spatial-angular
      filtering efficiency criterion. Some effective approaches to achieve a high
      filtering efficiency for the receiving system optimization are discussed.

PMID- 12510916
TI  - Optical and physical properties of stratospheric aerosols from balloon
      measurements in the visible and near-infrared domains. 1. Analysis of aerosol
      extinction spectra from the AMON and SALOMON balloonborne spectrometers.
AB  - Aerosol extinction coefficients have been derived in the 375-700-nm spectral
      domain from measurement in the stratosphere since 1992, at night, at mid- and
      high latitudes from 15 to 40 km, by two balloonborne spectrometers, Absorption
      par les Minoritaires Ozone et NO(chi) (AMON) and Spectroscopie d'Absorption
      Lunaire pour l'Observation des Minoritaires Ozone et NO(chi) (SALOMON). Log
      normal size distributions associated with the Mie-computed extinction spectra
      that best fit the measurements permit calculation of integrated properties of the
      distributions. Although measured extinction spectra that correspond to background
      aerosols can be reproduced by the Mie scattering model by use of monomodal log
      normal size distributions, each flight reveals some large discrepancies between
      measurement and theory at several altitudes. The agreement between measured and
      Mie-calculated extinction spectra is significantly improved by use of bimodal log
      normal distributions. Nevertheless, neither monomodal nor bimodal distributions
      permit correct reproduction of some of the measured extinction shapes, especially
      for the 26 February 1997 AMON flight, which exhibited spectral behavior
      attributed to particles from a polar stratospheric cloud event.

PMID- 12510917
TI  - Optical and physical properties of stratospheric aerosols from balloon
      measurements in the visible and near-infrared domains. II. Comparison of
      extinction, reflectance, polarization, and counting measurements.
AB  - The physical properties of stratospheric aerosols can be retrieved from optical
      measurements involving extinction, radiance, polarization, and counting. We
      present here the results of measurements from the balloonborne instruments AMON,
      SALOMON, and RADIBAL, and from the French Laboratoire de Meteorologie Dynamique
      and the University of Wyoming balloonborne particle counters. A cross comparison
      of the measurements was made for observations of background aerosols conducted
      during the polar winters of February 1997 and January-February 2000 for various
      altitudes from 13 to 19 km. On the one band, the effective radius and the total
      amount of background aerosols derived from the various sets of data are similar
      and are in agreement with pre-Pinatubo values. On the other hand, strong
      discrepancies occur in the shapes of the bimodal size distributions obtained from
      analysis of the raw measurement of the various instruments. It seems then that
      the log-normal assumption cannot fully reproduce the size distribution of
      background aerosols. The effect ofthe presence of particular aerosols on the
      measurements is discussed, and a new strategy for observations is proposed.

PMID- 12510918
TI  - Redesign and improved performance of the tropospheric ozone lidar at the Jet
      Propulsion Laboratory Table Mountain Facility.
AB  - Improvements to the tropospheric ozone lidar at the Jet Propulsion Laboratory
      Table Mountain Facility for measurements of ozone profiles in the troposphere and
      lower stratosphere, between approximately 5-and 20-km altitude, are described.
      The changes were primarily related to the receiver optical subsystems and the
      data-acquisition system. The original 40-cm Cassegrain telescope was replaced
      with a faster (f/3) 91-cm Newtonian mirror. In the focal plane of this mirror,
      the lidar signal is divided into two parts by use of two separate optical fibers
      as field stops corresponding to different but neighboring 0.6-mrad fields of
      view. We then separate the two received wavelengths by aligning each transmitted
      beam to one of the fibers. In addition, two 50-mm telescopes are used for the
      collection of near-range returns. The four optical signals are brought to a
      chopper wheel for independent signal selection in the time and range domain. For
      each channel, an interference filter is used for skylight rejection and
      additional cross-talk prevention. The signals are detected with miniature
      photomultiplier tubes and input to a fast photon-counting system. The goals of
      these modifications were to increase the spatial and temporal resolution of the
      lidar, to extend the altitude range covered, to improve the quality of the raw
      data, and to enable regular and routine operation of the system for long-term
      measurements.

PMID- 12510919
TI  - High-energy, all-solid-state, ultraviolet laser power-amplifier module design and
      its output-energy scaling principle.
AB  - We demonstrate that a coaxially pumped, large-aperture ultraviolet power
      amplifier module with solid-state tunable laser medium Ce(3+):LiCaAlF6 has 98-mJ,
      290-nm, and 3-ns output pulses with a sufficient extraction efficiency of 25%.
      The detailed information of design parameters, including the gain-coefficient
      dependence on pump condition, is successfully accumulated for further energy
      scaling for a terawatt-class ultraviolet chirped pulse amplification laser system
      or a high-pulse-energy laser system.

PMID- 12510920
TI  - Investigation of thermal and optical properties of distributed Bragg reflectors
      by photothermal deflection spectroscopy.
AB  - We present the study of thermal and optical properties of 15.5 pair of
      GaAlAsSb/AlAsSb layers deposited upon a GaSb substrate by photothermal deflection
      spectroscopy. This stacking of layers constitutes a distributed Bragg mirror.

PMID- 12510921
TI  - Automatic output-beam-collimating configuration for high-average-power multirod
      resonator-amplifier systems.
AB  - A novel configuration for a multirod solid-state laser system is proposed. We
      stabilize the thermal-lens-dependent variation in the output-beam parameters by
      extracting the laser beam from the collimating point of periodic beam
      propagation. The performance is confirmed with a 100-W class diode-pumped Nd:YAG
      laser-amplifier system to demonstrate tenfold stabilization of the output-beam
      diameter.

PMID- 12510922
TI  - Quasi-continuous-wave birefringence-compensated single- and double-rod Nd:YAG
      lasers.
AB  - Compensation of thermally induced birefringence directed toward compensation of
      depolarization and bifocusing in laser rods is treated with simple beam transfer
      matrices. When we apply a 90-deg polarization-rotating element to a resonator,
      the radial and the tangential eigensolutions of the resonator change
      significantly. The effect of this alteration on the resonator's stability is
      investigated in detail. The outcome is used to design a single- and double-rod
      resonator resulting in 53 W with an M2 approximately 1.5 and 182 W of output
      power with an M2 approximately 1.2, respectively.

PMID- 12510923
TI  - Demonstration of a 1-W injection-locked continuous-wave titanium:sapphire laser.
AB  - We report on a 1-W injection-locked cw titanium:sapphire ring laser at 846 nm.
      Single-frequency operation requires only a few milliwatts of injected power. This
      relatively simple and inexpensive system can be used for watt-level single
      frequency lasers across most of the titanium:sapphire gain region. A brief review
      of injection-locking theory is given, and conclusions based on this theory
      indicate ways to improve the performance of the system.

PMID- 12510924
TI  - Optical power flow in plastic-clad silica fibers.
AB  - Using the time-independent power-flow equation, we have examined the mode
      coupling caused by intrinsic perturbation effects of step-index plastic clad
      silica fiber carrying more than 10(5) modes. Result show that the equilibrium
      mode distribution for this fiber is achieved at a length of approximate 550 m,
      which is longer than reported previously. While this coupling length is much
      longer than that of plastic optical fibers, it is sorter than that of all-glass
      fibers.

PMID- 12510925
TI  - Minimization of acquisition time in short-range free-space optical communication.
AB  - We consider short-range (1-3-km) free-space optical communication between moving
      parties when covertness is the overriding system performance requirement. To
      maximize covertness, it is critical to minimize the time required for the
      acquisition phase, during which the party initiating contact must conduct a broad
      field scan and so risks revealing his position. Assuming an elliptical Gaussian
      beam profile, we show how to optimize the beam divergence angles, scan speed, and
      design of the raster scan pattern so as to minimize acquisition time. In this
      optimization, several constraints are considered, including signal-to-noise
      ratio, required for accurate bearing detection and reliable decoding; limited
      receiver bandwidth; limited scanner speed; and beam divergence as limited by the
      scanner mirror dimensions. The effects of atmospheric turbulence are also
      discussed.

PMID- 12510926
TI  - Metal-covered photonic bandgap multilayer for infrared hollow waveguides.
AB  - Infrared hollow waveguides utilizing a dielectric multilayer are examined by use
      of a photonic bandgap theory. It is shown that, in the waveguide consisting of
      quarter-wave film stack, the act of covering the dielectric films with a metal
      layer is effective in the reduction of the number of film layers. To verify the
      effect of this design, we fabricated a prototype waveguide with three dielectric
      layers of SiO2/Ta2O5/SiO2 and a silver layer by using a liquid-phase coating
      technique. From the loss spectrum of the fabricated waveguide, it is confirmed
      that, as designed, the waveguide shows wideband low-loss property at the
      wavelength of Nd:YAG laser light 1.06 microm.

PMID- 12510927
TI  - Monitoring and multiplexing technique for interferometric fiber optic sensors
      with a linearly chirped Er:fiber laser.
AB  - The monitoring of interferometer fiber optic sensors using a laser that is
      scanned over a wide frequency range is investigated. The interrogation technique
      is based on the principle that if the light-source frequency varies linearly with
      time, the optical signal reflected or transmitted is intensity modulated at a
      frequency that is proportional to the optical path difference (OPD) in the
      interferometer. Fourier components in the detected optical output signal then
      correspond to the OPDs of any interferometers that have contributed to this
      modulation. The temporal position of a peak in the power spectrum of this signal
      is proportional to the OPD of the interferometer that is responsible for that
      peak. A fine tuning of the OPD value is determined from the phase of the
      corresponding Fourier component. Experimentally, an Er:fiber laser scanned over a
      48-nm range centered at 1540 nm was used to monitor intrinsic fiber Fabry-Perot
      interferometers (FFPIs). Variations in the laser scan rate were compensated with
      the optical signal modulated by a reference FFPI held at a constant temperature.
      The OPD measurement resolution was 3.6 nm, and the dynamic range was 1.3 x 10(7).
      The temperature was measured from 20 degrees C to 610 degrees C with a 0.02
      degrees C resolution, and multiplexing of three of the sensors arranged in series
      was demonstrated.

PMID- 12510928
TI  - Image transfer through cirrus clouds. II. Wave-front segmentation and imaging.
AB  - A hybrid technique to simulate the imaging of space-based objects through cirrus
      clouds is presented. The method makes use of standard Huygens-Fresnel propagation
      beyond the cloud boundary and a novel vector trace approach within the cloud. At
      the top of the cloud, the wave front is divided into an array of input gradient
      vectors, which are in turn transmitted through the cloud model by use of the
      Coherent Illumination Ray Trace and Imaging Software for Cirrus. At the bottom of
      the cloud, the output vector distribution is used to reconstruct a wave front
      that continues propagating to the ground receiver. Images of the object as seen
      through cirrus clouds with different optical depths are compared with a
      diffraction-limited image. Turbulence effects from the atmospheric propagation
      are not included.

PMID- 12510929
TI  - Two-step K(+)-Na+ and Ag(+)-Na+ ion-exchanged glass waveguides for C-band
      applications.
AB  - A two-step K(+)-Na+ and Ag(+)-Na+ ion-exchange technique is introduced to
      fabricate single-mode channel waveguides in BK7 glass for the telecom-wavelength
      region. The dependencies of insertion loss, polarization-dependent loss (PDL),
      end bending loss of curved waveguides on channel width, diffusion time, and
      annealing time are investigated. Results show that postannealing is a required
      process for improving waveguide properties and an optimal annealing time exists.
      Although relatively narrow mask openings are used in most one-step ion-exchange
      processes, a wider channel width, to as wide as 10 microm, is preferred for this
      two-step method. The minimum coupling loss to/from single-mode fiber and the
      propagation loss is found to be 0.4 dB and 0.3 dB/cm, respectively. For 5-cm-long
      waveguides the PDL is less than 0.1 dB. For the S-bend structure the cosine curve
      exhibit apparently a lower bending loss than the double-arc curve.

PMID- 12510930
TI  - Thermally induced nonlinear optical effects in an isotropic liquid crystal at
      10.6 microm.
AB  - We investigate thermally induced nonlinear optical effects on a CO2 laser beam
      that passes through an isotropic liquid crystal film. We evaluate the thermal
      nonlinear coefficient of the refractive index at a wavelength of 10.6 microm by
      means of a thermographic technique combined with an optical method based upon the
      measurement of the self-defocusing effect caused by the heating of the liquid
      crystal induced by the laser beam. The novelty of our work is the application of
      thermography in order to measure the temperature field on the liquid crystal film
      caused by the partial absorption of the laser radiation by the liquid crystal.
      These measurements provide a precise evaluation of the thermal diffusion lengthof
      the liquid crystal under investigation. Moreover, thermography results in a
      straightforward experimental technique that can be used to investigate the
      thermal properties of a wide class of other fluids.

PMID- 12510931
TI  - Enhanced optical limiting and nonlinear absorption properties of azoarene
      appended phosphorus (V) tetratolylporphyrins.
AB  - Optical limiting performance, third-order nonlinearity chi(3), and nonlinear
      absorption properties have been investigated in a new class of azoarene
      phosphorus (V) porphyrins with charge transfer (CT) states. The introduction of
      axial azoarene groups into the phosphorus porphyrin structure is found to reduce
      the limiting threshold by a factor of 2 and lead to a rise in the second
      hyperpolarizability by 1 order of magnitude in the picosecond time regime and by
      2 orders of magnitude in the nanosecond regime. The experimental data show
      reverse saturation of absorption in the nanosecond time regime and a saturation
      of the nonlinear absorption above a fluence of 0.5 J/cm2 in the picosecond
      regime. The presence of the CT state reduces saturation of excited-state
      absorption (ESA) in the S1 --> Sn transition through the S1 --> CT transition.
      Faster CT --> T1 transition increases the ESA from T1 --> Tn states in the
      nanosecond regime. A self-consistent theoretical analysis based on rate equations
      is used to estimate the high-lying excited-state lifetimes and absorption cross
      sections from the experimental results.

PMID- 12510932
TI  - Brewster's angle attenuator for terahertz pulses.
AB  - A variable attenuator for terahertz (THz) pulses is developed on the basis of the
      change in reflectivity of lithium niobate wafers with incident angle in a
      Brewster configuration. We can vary the THz field transmission from 22% to 54%, a
      change of a factor of 2.5, while preserving the shape of the THz pulse spectrum.
      Changes in the THz spectrum are shown to be much smaller when the Brewster
      attenuator is used than when either the near-infrared pump power or the bias
      voltage on a THz photoconductive antenna is varied. The Brewster attenuator
      should prove especially useful for varying THz field strength in nonlinear
      optical studies that use broadband THz pulses.

PMID- 12510933
TI  - Optimal design method of a low-loss broadband Y branch with a multimode waveguide
      section.
AB  - An optimal design method for a low broadband silica-on-silicon Y branc is
      considered. A multimode waveguide section, which was used earlier to reduce the
      excess loss, is designed optimally when the light distribution at the end of the
      multimode waveguide section is matched to the profile of the symmetric supermode
      for the structure of the two branching waveguides. An optimization method that
      combines the genetic algorithm and a gradient-based search method is used to
      obtain the optimal geometrical parameters for the multimode waveguide section as
      well as the widths for the input and branching waveguides.

PMID- 12510934
TI  - Organic microcavity light-emitting diodes with metal mirrors: dependence of the
      emission wavelength on the viewing angle.
AB  - Organic microcavity light-emitting diodes typically exhibit a blueshift of the
      emitting wavelength with increasing viewing angle. We have modeled the shift of
      the resonance wavelength for several metal mirrors. Eight metals (Al, Ag, Cr, Ti,
      Au, Ni, Pt, and Cu) have been considered top or bottom mirrors, depending on
      their work functions. The model fully take into account the dependence of
      thephase change that occurs on reflection on angle and wavelength for both s and
      p polarization, as well as on dispersion in the organic layers. Different
      contribution to the emission wavelength shift are discussed. The influence of the
      thickness of the bottom mirror and of the choice and thickness of the organic
      materials inside the cavity has been investigated. Based on the results obtained,
      guidelines for a choice of materials to reduce blueshift are given.

PMID- 12510935
TI  - Combined Raman lidar for the measurement of atmospheric temperature, water vapor,
      particle extinction coefficient, and particle backscatter coefficient.
AB  - The lidar of the Radio Science Center for Space and Atmosphere (RASC; Kyoto,
      Japan) make use of two pure rotational Raman (MR) signals for both the
      measurement of the atmospheric temperature profile and the derivation of a
      temperature-independent Raman reference signal. The latter technique is new and
      leads to significant smaller measurement uncertainties compared with the commonly
      used vibrational Raman lidar technique. For the measurement of temperature,
      particle extinction coefficient, particle backscatter coefficient, and humidity
      simultaneously, only four lidar signal are needed the elastic Cabannes
      backscatter signal, two RR signals, and the vibrational Raman water vapor signal.
      The RASC lidar provides RR signals of unprecedented intensity. Although only 25%
      of the RR signal intensities can be used with the present data-acquisition
      electronics, the 1-s -statistical uncertainty of nighttime temperature
      measurements is lower than for previous systems and is < 1K up to 11-km height
      for, e.g., a resolution of 500 m and 9 min. In addition, RR measurements in
      daytime also have become feasible.

PMID- 12510936
TI  - Correction to the plant canopy gap-size analysis theory used by the Tracing
      Radiation and Architecture of Canopies instrument.
AB  - A plant canopy gap-size analyzer, the Tracing Radiation and Architecture of
      Canopies (TRAC), developed by Chen and Cihlar [Appl Opt. 34, 6211(1995)] and
      commercialized and by 3rd Wave Engineering (Nepean, Canada), has been used around
      the world to quantify the fraction of photosynthetically activeradiation absorbed
      by plant canopies, the leaf area index (LAI), and canopy architectural
      parameters. The TRAC is walked under a canopy along transects to measure
      sunflecks that are converted into a gap-size distribution. A numerical gap
      removal technique is performed to remove gaps that are not theoretically possible
      in a random canopy. The resulting reduced gap-size distribution is used to
      quantify the heterogeneity of the canopy and to improve LAI measurements. It is
      explicitly shown here that the original derivation of the clumping index was
      missing a normalization factor. For a very clumped canopy with a large gap
      faction, the resulting LAI can be more than 100% smaller than previously
      estimated. A test case is used to demonstrate that the new clumping index
      derivation allows a more accurate change of LAI to be measured.

PMID- 12510937
TI  - Three-dimensional imaging laser radar with a photon-counting avalanche photodiode
      array and microchip laser.
AB  - We have developed a threedimensional imaging laser radar featuring 3-cm range
      resolution and single-photon sensitivity. This prototype direct-detection laser
      radar employs compact, all-solid-state technology for the laser and detector
      array. The source is a Nd:YAG microchip laser that is diode pumped, passively Q
      switched, and frequency doubled. The detector is a gated, passively quenched, two
      dimensional array of silicon avalanche photodiodes operating in Geigermode. After
      describing the system in detail, we present a three-dimensional image, derive
      performance characteristics, and discuss our plans for future imaging three
      dimensional laser radars.

PMID- 12510938
TI  - Optical modeling and measurements of a coccolithophore bloom.
AB  - Blooms of the phytoplankton coccolithophorid Emiliania huxleyi can cause
      significant changes to both the inherent and the apparent optical properties
      within an oceanic column. Measurements made within such a bloom off the
      southwestern coast of England during July 1999 are reported. The multiple
      scattering properties of the bloom prevented accurate retrieval of absorption (a)
      and attenuation (c) coefficients with a WETLabs ac-9. Upwelling radiance
      measurements were similarly affected by the bloom, which caused the sensors to
      saturate. An optical model has been developed that gives close agreement with the
      in situ optics when it is used as input to the Hydrolight radiative-transfer
      model.

PMID- 12510939
TI  - Coherent laser radar at 3.6 microm.
AB  - Coherent laser radar systems in the mid-IR wavelength region can have advantages
      in low-altitude environment because they are less sensitive to scattering,
      turbulence, and humidity, which can affect shorter- or longer-wavelength system.
      We describe a coherent laser radar at 3.6 microm based on a single-frequency
      optical parametric oscillator and demonstrate the system over short ranges
      outdoors. The system was used to make micro-Doppler measurements from idling
      trucks that were processed to give surface vibration spectra.

PMID- 12510940
TI  - Radiation force on a nonlinear microsphere by a tightly focused Gaussian beam.
AB  - We determine the characteristics of the radiation force that is exerted on a
      nonresonant nonlinear (Kerr-effect) rigid microsphere by a strongly focused
      Gaussian beam when diffraction and interference effects are significant (sphere
      radius a < or = illumination wavelength lambda). The average force is calculated
      from the surface integral of the energy-momentum tensor consisting of incident,
      scattered, and internal electromagnetic field vectors, which are expressed as
      multipole spherical-wave expansions. The refractive index of a Kerr microsphere
      is proportional to the internal field intensity, which is computed iteratively by
      the Rytov approximation (residual error of solution, 10(-30). The expansion
      coefficients for the field vectors are calculated from the approximated index
      value. Compared with that obtained in a dielectric (linear) microsphere in the
      same illumination conditions, we find that the force magnitude on the Kerr
      microsphere is larger and increases more rapidly with both a and the numerical
      aperture of the focusing objective. It also increases nonlinearly with the beam
      power unlike that of a linear sphere. The Kerr nonlinearity also leads to
      possible reversals of the force direction. The proposed technique is applicable
      to other types of weak optical nonlinearity.

PMID- 12510941
TI  - Analysis and observation, on an atomic resonance, of the frequency shift due to
      the length modulation of an optical cavity.
AB  - The frequency shift of the light owing to a cavity length modulation has been
      observed with the spectroscopy of the 1S-3S two-photon transition in hydrogen.
      The excitation of this transition occurs at a wavelength of 205 nm. One produces
      this radiation by frequency doubling a 410-nm radiation in an enhancement ring
      cavity. The length modulation of this cavity induces frequency shifts and a
      splitting of the observed 1S-3S line. We obtain a good agreement between the
      experiment and the theoretical analysis.

PMID- 12510942
TI  - The twists of fate--the role of chance--the joy of life.

PMID- 12510943
TI  - Is daily mvi required in patients receiving parenteral nutrition?
AB  - Between November 1996 and January 1999 there was a nationwide shortage of
      intravenous multivitamins (MVI) in the US. We investigated whether patients who
      received parenteral nutrition (PN) with MVI three times per week instead of daily
      developed clinical manifestations of vitamin deficiency during that period. Five
      patients were enrolled in the study All received home PN as their sole source of
      nutrition for at least six months. None of these patients showed clinical
      manifestations of vitamin deficiency. In addition, compared to daily MVI
      administration, supplementation with MVI three times per week saved $1,000 per
      patient per year. This preliminary study raises the question of how much MVI is
      needed to prevent vitamin deficiency. Using MVI three days a week instead of
      daily would substantially reduce the cost of treatment and might reduce the risk
      of infections for these patients.

PMID- 12510944
TI  - Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and
      flu symptoms and sore throat pain.
AB  - This double-blind randomised study compared the tolerability of ibuprofen (up to
      1.2 g daily), aspirin and paracetamol (both up to 3 g daily) for up to seven
      days, in patients with mild to moderate pain resulting from cold/flu symptoms or
      sore throat (CF/ST) (n = 2,815). The main outcome was the rate of significant
      adverse events (SGAE). Rates of SGAE for ibuprofen, aspirin and paracetamol were
      respectively 12.0%, 15.7% and 12.3%. Ibuprofen was significantly better tolerated
      than aspirin (p = 0.02) and had comparable tolerability with paracetamol. The
      latter was also true for total digestive system events and for abdominal pain and
      dyspepsia. In conclusion, in patients with CF/ST, ibuprofen used at over-the
      counter doses is as well tolerated as paracetamol and much better tolerated than
      aspirin.

PMID- 12510945
TI  - Shock waves do more than just crush stones: extracorporeal shock wave therapy in
      plantar fasciitis.
AB  - Heel pain is a common orthopaedic problem, The cause of this clinical entity
      remains an enigma. The overall prognosis is good, however, and the symptoms
      generally settle well with time. There appears to be little evidence of the
      effectiveness of local steroid injections and dorsiflexion night splints.
      Extracorporeal shock wave therapy (ECSW) has been used in orthopaedics since the
      1980s. With this, a new tool has become available for the treatment of plantar
      fasciitis, achillis tendinitis, shoulder pain and tendinosis of the elbow. In our
      pilot study we found good results with the use of ECSW therapy in resistant
      plantar fasciitis. Additional controlled studies are required to define the
      precise role of this new modality in the treatment of chronic plantar fasciitis.

PMID- 12510946
TI  - Twelve-year experience in the investigation and treatment of paragangliomas.
AB  - We report a 12-year laboratory experience in the diagnosis of 37 patients with
      phaeochromocytoma, one with malignant paraganglioma and one with
      ganglioneuroblastoma. Surgery was performed in eight different hospitals, which
      underlines the difficulty of ensuring uniformity of investigations. Of the 37
      with phaeochromocytoma, 15 were in the right adrenal gland, 12 were on the left,
      seven were bilateral and three were extra adrenal. Twenty-three were male and 15
      were female; the median age was 36 years. Four of five patients with von Hippel
      Lindau disease had bilateral adrenal tumours and four had neurofibromatosis. None
      had multiple endocrine neoplasia. Using essential hypertensive patients as a
      reference population, diagnostic sensitivity was 80% for noradrenaline, 54.4% for
      adrenaline, 19.1% for dopamine, 93.3% for total normetanephrine, 33.3% for total
      metanephrine, 78.7% for 3-methoxy-4-hydroxymandelic acid (HMMA) and 23.5% for
      homovanillic acid (HVA). However, if each patient's results were taken as a
      package, the sensitivities were 100% for noradrenaline, 63.6% for adrenaline,
      30.3% for dopamine and 89% for HMMA. Seven recent patients had gene analysis.
      There were six (15.4%) deaths due directly or indirectly to the paraganglioma.
      Postoperative blood pressures were normal in 74%. The decrement in catecholamine
      values post-surgery is shown. Urinary noradrenaline values fell by a mean of
      94.5% and the use of urinary noradrenaline as a tumour marker is also
      demonstrated.

PMID- 12510947
TI  - Management of hyperthyroidism in Trinidad and Tobago.
AB  - A questionnaire study of current practices regarding the investigation and
      treatment of hyperthyroidism was undertaken in Trinidad and Tobago between
      December 1999 and March 2000. The study evaluated the choice of laboratory tests
      requested and the therapeutic choices for a standard patient with
      hyperthyroidism. In addition, clinical scenarios based upon variations of the
      standard case (by altering age, gender, goitre size and duration of disease) were
      also tested. Two hundred and ninety-six questionnaires were sent; 134 (45%) were
      returned, of which four were excluded for incomplete data. Ninety five per cent
      of respondents requested biochemical confirmation but the range of tests varied
      widely. Thyroid scintigraphy was requested by 36% and thyroid ultrasound by 35%.
      Medical treatment (75%) with antithyroid drugs was the most popular choice for
      treatment of the standard patient. This did not change significantly if the
      patient was male. On the other hand, radioiodine (62%) was more popular in the
      treatment of chronic/relapsing hyperthyroidism (p < 0.005). In the elderly,
      medical management was still the most popular choice (57%) but the choice of
      radioiodine therapy was significantly increased compared with that in the
      standard patient (36% vs 19%) (p<0.005). In a young female with a large goitre
      and chronic disease, surgical intervention (61%) was the treatment of choice,
      especially among surgeons and general practitioners; radioiodine was chosen by
      28% of respondents (mostly internists). There is need for clear guidelines in
      investigating thyroid disease but therapeutic choices are well informed and
      consistent with accepted practice elsewhere. In particular there is a fairly
      liberal attitude towards radioiodine use in hyperthyroidism.

PMID- 12510948
TI  - 19. Male breast cancer: aetiology, genetics and clinical management.
AB  - Male breast cancer (MBC) is a rare disease with an older average age of
      presentation than in women. Predisposing factors include increased exposure to
      oestrogen and being a carrier of a BRCA2 mutation. Most MBC is ductal and the
      majority are oestrogen receptor positive. Modified radical mastectomy is the
      treatment of choice for local disease and adjuvant radio-, hormonal and
      chemotherapy should all be considered. Stage for stage, the prognosis for MBC is
      similar to that for female breast cancer. Despite a wealth of small retrospective
      studies on MBC, its rarity means there is a lack of prospective randomised
      controlled treatment trials, which needs to be addressed if significant advances
      are to be made in the treatment of this unusual and challenging disease.

PMID- 12510949
TI  - 20. Oral contraceptives, hormone replacement therapy and breast cancer.
AB  - Both oral contraceptives (OCs) and hormone replacement therapy (HRT) are widely
      used by healthy women, so that any increase in breast cancer has to be considered
      in relation to the avoidance of either pregnancy or menopausal symptoms. Use of
      OCs for more than four years before first full term pregnancy leads to a small
      but significant increase in risk of breast cancer (6.5 extra cases per 10,000
      women aged 20-29) that persists for 10 years after cessation. Risk is not
      amplified by a positive family history and OC-induced breast cancers are more
      likely to be localised to the breast. For those taking HRT there is an increased
      relative risk of breast cancer of 2.3% per year, similar to the increase in risk
      for each extra year spent in a premenopausal state. The increase in risk
      disappears five years after cessation. HRT does not lead to any increase in risk
      of dying of breast cancer. Some breast cancer patients can safely take HRT, and
      it is possible that some formulations may reduce the subsequent risk of relapse.

PMID- 12510950
TI  - High density lipoprotein: guardian of the vascular system?
AB  - The role of low-density lipoprotein in the development of coronary heart disease
      (CHD) is well recognised. There is also growing evidence that high-density
      lipoprotein cholesterol (HDL-C) is a powerful inverse predictor for premature CHD
      and that maintaining a high HDL-C level may guard against atherosclerosis.
      Patients with low HDL-C levels often also have central obesity, insulin
      resistance and other features of the metabolic syndrome. This syndrome is both
      increasingly common and strongly implicated in the growing worldwide epidemic of
      type 2 diabetes. HDL-C may be increased by lifestyle changes, e.g. weight loss,
      physical activity and smoking cessation. Pharmacological agents such as fibrates,
      niacin and statins have also been shown significantly to elevate HDL-C. Although
      current guidelines are beginning to recognise the protective role of HDL-C level
      in preventing coronary events, HDL-C should be adopted soon as a target for
      intervention in its own right.

PMID- 12510951
TI  - Matching the standards of clinical trial evidence with application in practice.
AB  - A high standard of proof of efficacy and safety is required in clinical trials.
      This standard requires careful translation into practice, combining an evidence
      based approach with clinical experience and judgment to maximise patient benefits
      and minimise harms. The tendency to extend application of new treatments to
      patient groups other than those for whom reliable data exist should be avoided.
      Equally, extrapolation of the data to agents of the same class untested for
      particular indications should not occur. If the considerable potential benefits
      of modern cardiovascular therapeutics are to be maximised and harms avoided,
      clinicians should observe these principles carefully as new treatments become
      accessible and are applied.

PMID- 12510952
TI  - The physiology and emerging roles of antidiuretic hormone.
AB  - The antidiuretic hormone (ADH) vasopressin is a simple peptide hormone with a
      number of complex, essential physiological actions. It is becoming clear that
      this hormone is developing an important therapeutic role in a number of different
      conditions. These include vasodilatory shock due to sepsis or cardiac surgery,
      cardiac arrest, and prolonged/excessive bleeding caused by, for example, variceal
      haemorrhage. This article reviews the physiology of ADH relevant to these actions
      and scrutinises the evidence for its therapeutic applications.

PMID- 12510953
TI  - From adrenaline to formoterol: advances in beta-agonist therapy in the treatment
      of asthma.
AB  - Long-acting beta2-agonists (formoterol and salmeterol) represent the latest
      advance in a series of improvements in beta-agonist asthma therapy since the
      introduction of isoprenaline. Traditional inhaled short-acting beta2-agonists
      (salbutamol and terbutaline) provide rapid as-needed symptom relief and short
      term prophylactic protection against bronchoconstriction induced by exercise or
      other stimuli. Where symptoms are not adequately controlled by corticosteroids
      alone, inhaled selective long-acting beta2-agonists are used additionally for
      maintenance. Salmeterol and formoterol are well tolerated, provide effective long
      term symptom control and reduce the incidence of exacerbations; any development
      of tolerance or masking of underlying inflammation with continual use does not
      appear to be clinically relevant. Formoterol is both rapid acting (as fast as
      salbutamol) and long acting (similar to salmeterol). Increasing clinical evidence
      suggests that inhaled formoterol is a convenient and well-tolerated treatment
      that is effective both for regular maintenance and as-needed relief of symptoms.

PMID- 12510954
TI  - Rivastigmine in patients with Alzheimer's disease and concurrent hypertension.
AB  - Rivastigmine has demonstrated significant benefits in patients with mild to
      moderate Alzheimer's disease (AD). We aimed to confirm whether rivastigmine was
      effective in patients with or without concurrent vascular risk factors (VRF), as
      previously suggested. We chose to stratify the 725 patients involved in an
      international dose-ranging study according to the presence of arterial
      hypertension (a marker of VRF) at baseline. Efficacy in each subgroup was
      assessed using the ADAS-cog, a measure of cognitive performance, the Progressive
      Deterioration Scale (PDS) and the Clinician's Interview-Based Impression of
      Change (CIBIC) with caregiver input. Patients receiving rivastigmine 6-12 mg/day
      showed better outcomes on the ADAS-cog than those receiving placebo, in both the
      hypertensive and non-hypertensive subgroups. Hypertensive patients receiving
      rivastigmine 6-12 mg/day also showed improvement over those receiving 1-4 mg/day
      (p = 0.023). Rivastigmine 6-12 mg/day also provided better outcomes than placebo
      on the PDS in the hypertensive (p = 0.031) and non-hypertensive (p = 0.035)
      subgroups. All patients receiving rivastigmine 6-12 mg/day had superior CIBIC
      plus scores than those receiving placebo. There was a trend for lower incidences
      of nausea and vomiting in rivastigmine-treated patients with hypertension than in
      those without hypertension. No cardiac adverse events or drug-drug interactions
      were reported. Our data support the hypothesis that rivastigmine provides
      benefits to patients with or without hypertension, and contribute to the evidence
      that particular benefits may be observed in those with vascular risk factors.

PMID- 12510955
TI  - Symbicort Turbuhaler: a new concept in asthma management.
AB  - Symbicort is a novel asthma product containing both budesonide and formoterol in
      a single inhaler, Turbuhaler. Budesonide is a corticosteroid that treats
      underlying airway inflammation in asthma; formoterol is a rapid- and long-acting
      beta2-agonist that prevents and reverses airway obstruction. Budesonide and
      formoterol therefore have complementary effects, treating two different
      components of asthma. Clinical studies have shown that Symbicort is more
      effective in the treatment of asthma than double-dose corticosteroid, and
      clinical experience to date indicates that Symbicort is at least as effective and
      well tolerated as budesonide and formoterol given in separate inhalers. Symbicort
      has a fast onset of effect, which may help patients feel more in control of their
      condition and improve adherence to their medication, and a long duration of
      effect that allows twice-daily or even once-daily dosing during periods of good
      control. More convenient treatment represents another important benefit for
      patients with asthma, as ease of use can also result in improved adherence,
      leading to better disease control.

PMID- 12510956
TI  - A hyaluronan preparation (500-730 kDa) in the treatment of osteoarthritis: a
      review of clinical trials with Hyalgan.
AB  - The purpose of this paper is to review the intra-articular treatment of
      osteoarthritis (OA) of the knee with the hyaluronan preparation 500-730 kDa
      (Hyalgan). Reviewing the results of 24 clinical trials, it can be concluded that
      3-5 weekly injections of Hyalgan significantly improve the pain and functional
      status of patients with OA. Although the onset of improvement is delayed by 3-4
      weeks, the effect can last at least six months and up to one year after treatment
      cessation. The benefits of Hyalgan compared with intra-articular corticosteroids
      are also addressed. The potential for Hyalgan to have a structure-modifying
      action by retarding stuctural progression in OA of the knee is considered.
      However, further studies of Hyalgan in OA in other joints, and in damaged joints
      in rheumatoid arthritis, are needed.

PMID- 12510957
TI  - Upper airway obstruction resulting from an antiemetic.
AB  - Stridor and stertor can both be the cause of medical and surgical emergencies.
      The management of these conditions is largely dependent upon the underlying
      aetiology. This case report describes dystonia following prochlorperazine
      resulting in stridor and stertor.

PMID- 12510958
TI  - Double dislocation of the proximal and distal interphalangeal joints of the
      little finger.
AB  - A 32-year-old amateur goalkeeper sustained simultaneous dislocation of the
      proximal and distal interphalangeal joints following a hyperextension injury.
      This was reduced under a digital nerve block. Neighbour finger strapping and
      early mobilisation achieved a full range of movements at both joints when
      reviewed three weeks after the initial injury.

PMID- 12510959
TI  - Folk remedies still in use: a case of soft palate and uvular oedema due to
      Ecbalium elaterium.
AB  - A case of soft palate and uvular oedema due to nasal administration of juice
      produced from the fruit of the plant Ecbalium elaterium, widely known as
      squirting cucumber, is presented. The patient recovered after administration of
      subcutaneous adrenaline and methylprednisolone. Cucurbitacins have been
      implicated in the past as toxic constituents of plants from the Cucurbitaceae
      family. Either an allergic reaction or a direct toxic effect of the constituents
      is responsible for the occurrence. A few similar cases have been reported, mostly
      in eastern Mediterranean countries.

PMID- 12510960
TI  - Twin reversed arterial perfusion (TRAP) syndrome.
AB  - Twin reversed arterial perfusion (TRAP) syndrome is an extremely rare
      manifestation of feto-fetal transfusion syndrome. This condition is seen in
      monozygotic twin pregnancies, where the affected twin is perfused retrogradely by
      the healthy twin. The affected twin presents with bizarre malformations such as
      acardia and acephalus. We present such a case, which was diagnosed prenatally.
      The pregnancy progressed uneventfully to term.

PMID- 12510961
TI  - Escape mechanisms in tumor immunity: an update.
AB  - Evidence that tumors are immunogenic continues to accumulate. Although they
      frequently do express antigens in a form recognizable by the host immune system,
      tumors commonly "escape" the immune response. Tumors may therefore progress by
      evolving variants that can evade immune responses or by developing other
      strategies to avoid immune control. The purpose of this review is to consider the
      current status of knowledge concerning these different tumor-escape strategies,
      in the form of an update of previous publications in this journal.

PMID- 12510962
TI  - Arsenic-mediated cellular signal transduction, transcription factor activation,
      and aberrant gene expression: implications in carcinogenesis.
AB  - Arsenic is a common environmental and occupational pollutant and a well-known
      human carcinogen that causes cancers in many human organs. The exact molecular
      mechanisms of arsenic carcinogenesis, however, are not well understood. It is
      generally acknowledged that arsenic does not act via a classic genotoxic or
      mutagenic mechanism, because it is not a direct mutagen. On the other hand, a
      growing amount of evidence has shown that arsenic shares many properties with
      tumor promoters by inducing intracellular signal transduction, activating
      transcription factors, and changing the expression of genes that are involved in
      promoting cell growth, proliferation, and malignant transformation. It is
      postulated that arsenic-induced mitogen-activated protein kinases (MAPKs) signal
      transduction, which leads to activation of transcription factors such as
      activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB) (which in turn
      alter gene expression), is associated with the carcinogenicity of arsenic. In
      this article, we review the recent findings in arsenic-induced MAPKs, AP-1 and NF
      kappaB activation, and aberrant gene expression; their implications in arsenic
      carcinogenesis are discussed. The elucidation of arsenic-induced signal
      transduction pathways that lead to aberrant gene expression involved in the
      arsenic-triggered malignant transformation could help to identify novel molecular
      targets for the treatment of human cancers resulting from arsenic exposure.

PMID- 12510963
TI  - Role of neutrophil apoptosis in vanadium-induced pulmonary inflammation in mice.
AB  - Pulmonary exposure to airborne vanadium and vanadium-containing compounds is
      associated with acute pulmonary inflammation, characterized by a rapid influx of
      neutrophilic polymorphonuclear leukocytes with a peak response at 6 hours and
      resolution by 3 days. We hypothesized that neutrophil apoptosis is involved in
      the resolution of vanadium-induced lung inflammation. To test this hypothesis,
      mice were exposed to inspired vanadium or saline control and the bronchoalveolar
      lavage (BAL) cells were examined at various times for apoptosis using terminal
      deoxyribonucleotidyl transferase-mediated nick end labeling (TUNEL). Control mice
      showed only resident alveolar macrophages in the BAL with no evidence of
      apoptosis. In contrast, vanadium-treated mice showed clear apoptosis of BAL
      cells, which were predominantly neutrophils. The number of apoptotic cells
      gradually increased and reached a maximal level by 24 hours with subsequent
      decline. After 24 hours, when the vanadium-induced lung inflammation was in the
      resolution phase, we observed an increased number of alveolar macrophages in BAL
      and the engulfment of apoptotic bodies by these macrophages. At 72 hours, the
      total number of neutrophils in BAL fell to the baseline level, and the number of
      apoptotic cells was reduced. Clearance of the apoptotic product was demonstrated
      by the presence of apoptotic bodies in the cytoplasm of alveolar macrophages. We
      conclude that apoptosis of neutrophils and clearance by alveolar macrophages are
      important mechanisms in the resolution of vanadium-induced lung inflammation.

PMID- 12510964
TI  - Gastro-oesophageal cancer: facts, myths and surgical folk lore.
AB  - The prognosis of patients with gastric and oesophageal cancers remains poor but
      increased knowledge of the factors involved in carcinogenesis and a better
      understanding of the disease process has led to strategies to improve outcomes.
      These are discussed under the following headings: (1) Prevention of the disease,
      (2) early detection of tumours, (3) treatment selection and (4) treatment. The
      likely impact of developments in each of these areas is considered in relation to
      population-based data from the Scottish Audit of Gastro-Oesophageal Cancer
      (SAGOC). Although there are a number of novel developments in the management of
      gastric and oesophageal cancer it is only by the conduct of controlled trials
      that the value of these will be determined. More immediate improvements in
      patient care may be derived from rationalisation of existing resources to ensure
      that all patients benefit from early diagnosis, the appropriate selection and
      delivery of treatment. One model of care, which may ensure this is the
      development of managed clinical networks, would maintain the involvement of all
      units in the management and treatment of upper GI cancers to a level that is
      possible with the facilities available. At the same time the patients requiring
      more specialised treatment would benefit from established referral networks

PMID- 12510965
TI  - Iatrogenic splenic injury.
AB  - BACKGROUND: Iatrogenic injury to the spleen is a recognised complication of
      abdominal surgery but the extent of the problem is often under-estimated. This
      may be due to failure to report splenic injury on the operation note or
      inaccurate recording of the indication for splenectomy. In this review article we
      have tried to estimate the incidence of iatrogenic splenic injury during
      abdominal surgery, the morbidity and mortality associated with splenic injury and
      the risk factors for injury to the spleen. We have also identified the common
      types and mechanisms of injury to the spleen and have made suggestions as to how
      splenic injury can be avoided and, when it occurs, how it should be managed.
      METHODS: A Medline literature search was performed to identify articles relating
      to "incidental splenectomy", "iatrogenic splenic injury", "iatrogenic
      splenectomy" and "splenectomy as a complication of common abdominal procedures".
      The relevant articles from the reference lists were also obtained. RESULTS: Up to
      40% of all splenectomies are performed for iatrogenic injury. The risk of splenic
      injury is highest during left hemicolectomy (1-8%), open anti-reflux procedures
      (3-20%), left nephrectomy (4-13%) and during exposure and reconstruction of the
      proximal abdominal aorta and its branches (21-60%). Splenic injury results in
      prolonged operating time, increased blood loss and longer hospital stay. It is
      also associated with a two to ten-fold increase in infection rate and up to a
      doubling of morbidity rates. Mortality is also reported to be higher in patients
      undergoing splenectomy for iatrogenic injury. The risk of injury to the spleen is
      higher in patients who have previously undergone abdominal surgery, in the
      elderly and in obese patients. A transperitoneal approach significantly increases
      the risk of splenic injury during left nephrectomy compared with an
      extraperitoneal approach and the risk is even higher if the indication for
      surgery is malignancy. Excessive traction, injudicious use of retractors and
      direct trauma are the commonest mechanisms of injury. CONCLUSIONS: The incidence
      of iatrogenic splenic injury is underestimated because of poor documentation.
      Splenic injury during abdominal surgery can be reduced by achieving good exposure
      and adequate visualisation, avoiding undue traction and by early careful division
      of splenic ligaments and adhesions. When the spleen is injured splenic
      preservation is desirable and often feasible, but this should not be at the
      expense of excessive blood loss

PMID- 12510966
TI  - Asymptomatic gallstones in the laparoscopic era.
AB  - Recent introduction of new treatment options has significantly altered the
      approach towards gallstone management. There is now general agreement that
      cholecystectomy is the treatment of choice for symptomatic gallstones.
      Controversy, however, exists as to the management of asymptomatic gallstones. The
      ready availability of abdominal ultrasonography for the investigation of a wide
      range of abdominal symptoms has resulted in the increased diagnosis of
      asymptomatic gallstones. Management of such accidentally discovered gallstones
      poses a dilemma as conclusive evidence of the benefits of cholecystectomy is
      lacking. This is further complicated by the fact that the majority of
      asymptomatic gallstones remain so and patients rarely experience symptoms or
      complications. Furthermore, cholecystectomy is associated with a low but
      recognised morbidity. Recent introduction of laparoscopic cholecystectomy as the
      treatment of choice of symptomatic gallstones has further complicated the issue
      of asymptomatic gallstone management. This article reviews the current management
      of asymptomatic gallstones in the era of laparoscopic cholecystectomy

PMID- 12510967
TI  - Cellular transplantation: new horizons in the surgical management of heart
      failure.
AB  - End-stage heart failure results from the irreversible destruction of
      cardiomyocytes, which do not have the capacity to regenerate. Transplantation of
      myogenic cells into the damaged myocardium is an emerging therapeutic alternative
      in the management of this major public health problem. Experimental and clinical
      data suggest that cellular transplantation could improve ventricular function in
      ischaemic or dilated cardiomyopathies. Implantation of allogeneic and autologous
      cell types has been applied to induce cardiac myogenesis and, recently, other
      cell types have been tested for the induction of myocardial angiogenesis. The
      results of cellular transplantation are encouraging although the role of
      therapeutic angiogenesis remains to be clarified and the full potential of
      cellular transplantation to be determined

PMID- 12510968
TI  - Clinical and functional results of open operative repair for Achilles tendon
      rupture in a non-specialist surgical unit.
AB  - We followed up 25 patients (average age 47.9 years, range 22 to 77) after open
      repair of their Achilles tendon rupture. All had been operated on by a single
      general surgeon using an end-to-end reabsorbable suture, and immobilised in a
      plaster of Paris cast for six weeks. All patients had been discharged from follow
      up by 18 weeks from the operation. At an average of 3.4 years (range six months
      to 9.25 years), 18 had "excellent", six (24%) "good" and one (4%) "satisfactory"
      results. All but one patient were able to walk on tiptoes, and 20 of the 22
      patients examined directly walked without a limp. Ultrasonography showed the
      injured tendons to be on average 2.3 times thicker in the antero-posterior
      diameter and 1.7 times thicker in the transverse diameter. In the hands of a
      single non-specialist but fully trained general surgeon, this management regimen
      produced full return to pre-operative activities in the majority of patients, and
      a low rate of local complications. The macroscopic and ultrasonographic
      appearance of the operated tendon remained abnormal, but this was not associated
      with any overt clinical disturbance

PMID- 12510969
TI  - Penile metastasis: an unusual presentation of metastatic colonic cancer.
AB  - We report here an interesting presentation of a primary colonic carcinoma in a
      urological setting. A previously unknown case of colonic carcinoma presented with
      a lesion in the glans penis which was later diagnosed as a secondary deposit from
      colonic cancer. Penile involvement has been implicated as a metastatic site in
      several tumours. Although uncommon, this presentation is not unknown. A
      literature review of this unusual presentation has been performed and is
      summarised in the article

PMID- 12510970
TI  - A novel idea for the treatment of fistula-in-ano.

PMID- 12510971
TI  - The Dundee protocol for investigation of haematuria.

PMID- 12510972
TI  - Haematuria investigation based on a standard protocol: emphasis on the diagnosis
      of urological malignancy.

PMID- 12510973
TI  - Ghrelin: endocrine and non-endocrine actions.
AB  - Ghrelin, a 28-amino acid acylated peptide produced predominantly by the stomach,
      displays strong growth hormone (GH)-releasing activity via the hypothalamus
      pituitary GH secretagogue (GHS) receptors that are specific for synthetic GHSs.
      Ghrelin's discovery changed our understanding of GH regulation. Evidence
      indicates that ghrelin also acts on other central and peripheral receptors and
      has other actions, including stimulation of lactotroph and corticotroph
      secretion; effects on gastroenteropancreatic functions; and orexigenic,
      metabolic, cardiovascular, and antiproliferative effects. When GHSs were
      developed more than 20 years ago as synthetic molecules, it was suggested that
      orally active GHSs might serve as alternatives to recombinant human GH for the
      treatment of GH deficiency. This proved not to be the case, however, and their
      utility as anabolic anti-aging agents to restore the GH-insulin-like growth
      factor-I axis during somatopause remains unclear. There is today, however, the
      possibility that GHS analogues could become candidate drugs for the treatment of
      conditions unrelated to disorders of GH secretion.

PMID- 12510974
TI  - Catch-up growth: definition, mechanisms, and models.
AB  - Catch-up growth is characterized by height velocity above the limits of normal
      for age for at least 1 year after a transient period of growth inhibition; it can
      be complete or incomplete. Although catch-up growth can be expressed in terms of
      height velocity, the change in height standard deviation score is more
      appropriate. Catch-up growth is difficult to distinguish from the pubertal growth
      spurt. The increased growth rate following intrauterine growth retardation is
      usually called catch-up growth, although it does not meet all the criteria. It is
      not possible to know whether catch-up growth is complete for an individual child,
      but if final height is within the target range, it can be considered that catch
      up growth has probably been complete. In groups of patients, complete catch-up
      growth is expected to result in a mean final height close to the mean target
      height. Increased growth velocity due to growth hormone (GH) therapy is
      accurately called catch-up growth in children with GH deficiency but should be
      called growth enhancement in children with other disorders. Two hypotheses have
      been proposed to explain the mechanism of catch-up growth: the neuroendocrine
      hypothesis, for which no persuasive experimental data have been produced, and the
      growth plate hypothesis, which cannot explain the increased growth rate observed
      in human catch-up growth.

PMID- 12510975
TI  - Early spontaneous catch-up growth.
AB  - We explored factors related to early catch-up growth in healthy children in
      Goteborg, Sweden. Most (82.9%) infants born small for gestational age (SGA)
      showed catch-up growth during their first 6 months, and 94.3% reached a final
      height within the normal range. At 6 months, 21 SGA children remained short and
      45 non-SGA babies fell below the -2 SDS cutoff in height. Of these 66 short
      infants, 10 (15.2%) remained short into adulthood and 56 showed spontaneous catch
      up growth. Fetal growth should be defined by body size at 6 months of age rather
      than at birth because most SGA infants catch up before 6 months, and furthermore,
      fetal growth regulatory mechanisms, such as insulin-like growth factor-I and -II,
      are the primary growth-promoting factors until 6 months of age.

PMID- 12510976
TI  - Catch-up growth: new lessons for the clinician.
AB  - In 1963, Prader, Tanner, and von Harnack published a landmark article describing
      catch-up growth in children after illness or starvation. That same year, Tanner
      proposed a theory about catch-up growth based on a central regulatory principle
      that is 'informed' about an organism's height by means of a humoral factor. This
      led to the assumption that, when dissociation between a central age-appropriate
      set point for body size and actual body size occurs, an efferent signal is
      transmitted to growth tissue to stimulate growth that corresponds to age
      appropriate body size. Catch-up growth has been observed in a wide range of
      endocrinological, nutritional, medical, and emotional disturbances, and the
      underlying causes are complex and not always well understood. Recently, catch-up
      growth in four situations has attracted the attention of endocrinologists, as
      these situations provide useful lessons for the clinician: hypothyroidism, growth
      hormone deficiency, intrauterine growth retardation, and adoption of children
      born in developing countries and raised in Western societies.

PMID- 12510977
TI  - Growth without growth hormone.
AB  - A functioning growth hormone (GH)-insulin-like growth factor (IGF)-I axis is
      ordinarily essential for normal growth. In several physiological and
      pathophysiological conditions, however, growth without GH has been described. GH
      deficient newborns can have a length within the normal range, which suggests that
      other growth factors dominate longitudinal gain during gestation. Obese children
      grow at a normal rate despite their low serum GH levels and reduced response to
      pharmacological stimulation tests. Children with hypopituitarism secondary to
      craniopharyngioma resection may continue to grow and may even show growth rate
      acceleration if their weight increases significantly. Several possible mechanisms
      might underlie the growth stimulation in obese children, such as elevated levels
      of insulin and reduced levels of IGF binding protein-1. Recently, elevated leptin
      levels in obese children were found to affect the bone growth center, and it may
      be that leptin also participates in the growth without GH observed in obesity,
      especially after craniopharyngioma removal. Sex hormones stimulate growth in
      children with a normal GH-IGF-I axis. In the absence of GH, the sex hormones
      stimulate growth through a direct GH-independent effect on the bone growth
      centers. Leptin, insulin, and sex hormones locally activate the IGF system in the
      epiphyseal growth plate (EGP). Other, undiscovered hormones and growth factors
      may harbor the ability to directly influence the growth processes in the EGP.

PMID- 12510978
TI  - A growth prediction model for short children born small for gestational age.

PMID- 12510979
TI  - Development of a consensus statement on management of short children born small
      for gestational age.

PMID- 12510980
TI  - Effects of long-term GH treatment on insulin sensitivity and glucose tolerance.

PMID- 12510981
TI  - Imprinting disorders: non-Mendelian mechanisms affecting growth.
AB  - Most autosomal genes are expressed from both maternal and paternal alleles.
      However, imprinted genes are an example of non-Mendelian genetics, in which only
      one member of the gene pair is expressed and expression is determined by the
      parent of origin. Imprinted genes may account for 0.1-1% of all mammalian genes.
      At least 50 imprinted genes have been identified in humans, and imprinted genes
      frequently cluster under the control of an imprinting center. Many imprinted
      genes contribute to growth, either as growth factors, such as insulin-like growth
      factors (IGF2 in Beckwith-Wiedemann syndrome), or as growth inhibitors, such as
      the GRB10 gene in Russell-Silver syndrome. Imprinted genes have evolved over time
      in mammals to fine-tune the growth of the fetus. Paternally expressed genes
      generally enhance growth, whereas maternally expressed genes appear to suppress
      growth. In addition, normal and abnormal genomic imprinting and loss of
      heterozygosity contribute to a wide range of malignancies. A common process for
      controlling gene activity is methylation, which can be changed during male or
      female gametogenesis. Examples of classic human disorders related to genomic
      imprinting are Beckwith-Wiedemann syndrome (chromosome 11), Prader-Willi/Angelman
      syndromes (chromosome 15), Russell-Silver syndrome (chromosome 7), and Albright
      hereditary osteodystrophy (chromosome 20). Several of these disorders are
      discussed and illustrated.

PMID- 12510982
TI  - SHOX haploinsufficiency and its modifying factors.
AB  - SHOX (short stature homeobox-containing gene) is the first gene that has been
      shown to be relevant to the development of specific features in Turner's
      syndrome. This article reviews clinical findings in patients with SHOX
      haploinsufficiency caused by intragenic mutations, pseudoautosomal submicroscopic
      deletions, and cytogenetically recognizable Xp deletions. SHOX haploinsufficiency
      can result in not only short stature but also Turner skeletal features, such as
      cubitus valgus, short metacarpals, Madelung deformity, Leri-Weill
      dyschondrosteosis, high arched palate, and short neck. Rare Turner skeletal
      features such as Madelung deformity and Leri-Weill dyschondrosteosis are
      primarily facilitated by the bone-maturing effect of gonadal estrogens. Common
      Turner skeletal features such as short metacarpals, cubitus valgus, and various
      craniofacial and cervical skeletal stigmata are largely caused by a compressive
      effect of distended lymphatics and lymphedema on the developing skeletal tissues.

PMID- 12510983
TI  - The definition of the Y chromosome growth-control gene (GCY) critical region:
      relevance of terminal and interstitial deletions.
AB  - Deletions of the long arm of the Y chromosome are often associated with short
      stature and infertility. Initial mapping assignments to narrow down the
      localization of the Y chromosome growth-control gene, GCY, were based on
      molecular analysis of patients carrying a 46,XYq- karyotype as defined by classic
      karyotyping. Two non-overlapping critical regions for GCY were defined. To
      determine whether one or both of these regions contained GCY, adult patients with
      monocentric Yq- chromosomes were reinvestigated in detail. Fluorescence in situ
      hybridization (FISH) analysis showed that all patients previously defined as
      having a pure 46,XYq- karyotype were in fact mosaics, with cells containing an
      idic(Y) or ring(Y) chromosome in association with 45,X cells. This excluded
      patients with terminal deletions as reliable subjects of study to locate the
      stature gene on Yq. In contrast, detailed molecular deletion analysis of patients
      who had interstitial deletions of the long arm of the Y chromosome pointed
      unequivocally to a single region next to the centromere that had a possible
      impact on growth. No functional gene has been identified in this region.

PMID- 12510984
TI  - New GH-1 gene mutations: expanding the spectrum of causes of isolated growth
      hormone deficiency.
AB  - Estimates of the frequency of growth hormone deficiency (GHD) range from 1:4,000
      to 1:10,000. Most cases are sporadic and presumed to be secondary to one of a
      wide variety of causes. However, in families with consanguinity, or when a second
      case occurs in the same family, a genetic cause may be suspected. Four distinct
      familial types of isolated GHD (IGHD) have been well differentiated on the basis
      of inheritance, hormonal deficiencies, and molecular analyses. Two forms are
      inherited autosomal recessively (IGHD type IA and IB); one is inherited autosomal
      dominantly (IGHD type II); and one is inherited in an X-linked manner. This
      review focuses on the secretory pathway of GH and the possible mechanisms causing
      IGHD type II. In IGHD type II, the apparently same phenotype results from several
      distinct GH-1 gene alterations leading to different blockades within the
      secretory pathway. This type of IGHD, in addition to some other specific GH-1
      gene mutations, provides the most important opportunity for shedding light on
      cellular biological mechanisms beyond its description at the DNA/RNA level.

PMID- 12510985
TI  - Development and function of the human fetal adrenal cortex.
AB  - The development and function of the primate adrenal cortex are characterized by
      rapid growth, high steroidogenic activity, and a particular morphological
      appearance. The fetal adrenal glands grow rapidly and exponentially and at term
      are similar in weight to adult adrenals. From birth to 1 year their mass is
      reduced as they undergo a process of differentiation. Growth then remains slow
      until age 7 years. Thereafter, growth accelerates and the adrenals reach adult
      weight by the end of puberty. In the first trimester of gestation, fetal adrenal
      growth is thought to be independent of adrenocorticotropic hormone (ACTH), but
      after 15 weeks, ACTH is absolutely required for normal morphological and
      functional development. Other factors of fetal and/or placental origin, acting
      independently of or in conjunction with ACTH, are also required. Basic fibroblast
      growth factor, epidermal growth factor/transforming growth factor beta, and
      insulin-like growth factor (IGF)-I and -II, all acting in an autocrine and/or
      paracrine fashion, have been postulated to stimulate fetal adrenal cell
      proliferation. Corticotropin-releasing hormone may also play an important role in
      primate fetal adrenal function, primarily at the end of gestation. Finally, the
      estrogens are also important in the development of the pituitary-adrenal axis in
      primates.

PMID- 12510986
TI  - Advances in the understanding of the genetic basis of adrenal insufficiency.
AB  - Primary adrenal failure in a pediatric population most frequently results from
      autoimmune destruction of the gland. Recent discoveries regarding the genetic
      factors underlying this and other inherited causes of adrenocortical failure
      provide valuable insights into the molecular basis of adrenal development and
      function. Among these are the clinical syndromes resulting from defects in DAX-1
      and SF-1 and the functional defects caused by mutations in the ACTH receptor and
      the StAR protein. Adrenoleukodystrophy and the triple A syndrome result from the
      degenerative effects induced by failure of very long chain fatty acid metabolism
      in the former case and the unknown effects of a novel protein that is mutated in
      the latter case. This review summarizes these recent findings and briefly
      describes the possible pathogenetic mechanisms that they reveal.

PMID- 12510987
TI  - Congenital adrenal hyperplasia: phenotype and genotype.
AB  - Congenital adrenal hyperplasia (CAH) is a monogenic autosomal recessive condition
      manifested as a heterogeneous phenotype and caused by mutations in the CYP21 gene
      on chromosome 6p21.3. More than 50 mutations have been described, of which about
      10 types account for >90% of affected alleles. Concordance between genotype and
      phenotype is sufficiently robust to be of significant value in the diagnosis and
      management of the adrenal disorder. Knowledge of the genotype is essential in
      planning a strategy for prenatal treatment and useful in resolving diagnostic
      dilemmas in newborn screening programs, identifying nonclassic CAH in
      hyperandrogenic women with elevated 17-hydroxyprogesterone levels, and studying
      the role of 21-hydroxylase deficiency in adrenal 'incidentalomas'. CYP21
      genotyping is also valuable in defining the requirement for glucocorticoid and
      mineralocorticoid replacement from infancy to adulthood. More detailed gene
      sequencing of the noncoding as well as the coding regions, together with analysis
      of other genes involved in steroid hormone production and action, will
      potentially be a significant step toward the goal of tailoring treatment to each
      individual.

PMID- 12510988
TI  - Effects of glucocorticoids on the skeleton.
AB  - Glucocorticoids have profound effects on mineral metabolism and skeletal cell
      function, and an excess can lead to the development of short stature and
      osteoporosis. The most significant actions of glucocorticoids are on chondrocytes
      and bone-forming cells, where they act, directly and indirectly, and regulate the
      local synthesis of insulin-like growth factor-I.

PMID- 12510989
TI  - Metabolic effects of stopping growth hormone: body composition and energy
      expenditure.
AB  - Discontinuation of growth hormone (GH) treatment at the end of childhood growth
      in individuals with GH deficiency has been shown to be associated with markedly
      increasing fat mass and decreasing metabolic rate. The association of these
      findings with increased abdominal fat and adverse changes in lipid biochemistry
      suggests that without longer-term GH therapy into adult life, these individuals
      will be at increased risk for cardiovascular morbidity and mortality. However,
      the evidence that these adverse events do not arise in those shown to be GH
      sufficient on retesting emphasizes the principle that all individuals who
      received GH therapy for childhood-onset GH deficiency require careful re
      evaluation of their GH secretion when growth is completed.

PMID- 12510990
TI  - Skeletal consequences of discontinuation of growth hormone at final height.
AB  - In light of the well-described adult growth-hormone (GH) deficiency syndrome, the
      traditional clinical practice of discontinuation of GH therapy in GH-deficient
      adolescent patients at completion of linear growth requires re-evaluation. Peak
      bone mass, an important determinant of the subsequent risk of osteoporosis
      related fracture in later life, occurs several years after the completion of
      linear growth. Given that GH has important anabolic actions on bone,
      discontinuation of GH therapy at the completion of linear growth may have adverse
      consequences for the attainment of peak bone mass in adolescent GH-deficient
      patients. This paper discusses the role of GH in the attainment of peak bone mass
      and some of the accumulating evidence that cessation of GH at final height may
      compromise bone mineral accretion in GH-deficient adolescent patients.

PMID- 12510991
TI  - Continuation of growth hormone therapy versus placebo in transition-phase
      patients with growth hormone deficiency: impact on body composition, insulin
      sensitivity, and thyroid function.
AB  - In a placebo-controlled, parallel study of 18 patients with a mean age of 20
      years who had confirmed growth hormone (GH) deficiency, we evaluated body
      composition, insulin sensitivity, and glucose turnover at baseline (when all were
      receiving GH replacement); after 12 months of continued GH therapy or placebo;
      and after a 12-month open phase of GH therapy. In the placebo group, insulin
      sensitivity and fat mass increased and lipid oxidation decreased, whereas glucose
      oxidation increased (p <0.05). During the open phase, insulin sensitivity
      decreased in the former placebo group although body fat decreased and fat-free
      mass increased. Throughout the study, most hormonal and metabolic parameters
      remained unchanged in those receiving continued GH therapy. These results
      indicate that: 1-year discontinuation of GH therapy induces fat accumulation in
      GH-deficient adolescents without compromising insulin sensitivity; the beneficial
      effects of continued GH treatment on body composition do not fully counterbalance
      its direct insulin antagonistic effects; and GH replacement has favorable effects
      on iodothyronine metabolism and quality of life.

PMID- 12510992
TI  - Transitioning patients with childhood-onset growth hormone deficiency to
      treatment in adulthood.
AB  - The transition through adolescence into adult life is fraught with physical,
      psychological, and social issues, even for the individual without underlying
      medical conditions. For the patient with childhood-onset growth hormone
      deficiency, this transition represents a critical phase, as an increasing body of
      evidence supports the concept that growth hormone treatment should be continued
      throughout adult life. Major issues include the need for confirmation of the
      diagnosis of growth hormone deficiency, the appropriate dosage of growth hormone
      during the transitional phase, dose titration during treatment, monitoring of
      therapeutic benefit and potential adverse effects, and optimization of
      compliance.

PMID- 12510993
TI  - Detection of insulin resistance and its treatment in adolescents with polycystic
      ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) appears to be a lifelong disorder. The stigmata
      of insulin resistance, including obesity and premature adrenarche, may be early
      forms of its presentation. Girls with premature pubarche, characterized by
      elevated dehydroepiandrosterone levels and hyperinsulinemia, are at high risk for
      developing the full PCOS phenotype, including ovarian hyperandrogenism and
      chronic anovulation. Because PCOS is associated with a 40% prevalence of abnormal
      glucose tolerance, every adolescent patient should be evaluated regularly for
      glucose intolerance with a 2-hour oral glucose tolerance test and for lipid
      abnormalities with a fasting lipid profile. The role of insulin-sensitizing
      medications such as metformin in adolescents with PCOS is unclear; short-term
      studies suggest that these agents improve circulating androgens and ovulatory
      frequency. Primary prevention of diabetes mellitus and cardiovascular disease by
      lifestyle modification, including regular exercise and a balanced diet, is
      particularly important in adolescents, who have the opportunity to establish
      healthy habits before entering adulthood. The findings of diabetes prevention
      trials suggest that these interventions may be more efficacious than
      pharmacological therapy.

PMID- 12510994
TI  - Eating disorders in females: genetics, pathophysiology, and treatment.
AB  - The eating disorders anorexia nervosa and bulimia nervosa are best conceptualized
      as syndromes and are classified on the basis of the clusters of symptoms they
      present. According to the multidimensional model, eating disorders begin with
      dieting, which is propelled into a full-blown disorder by antecedent conditions
      of biological vulnerability and genetics, premorbid psychological
      characteristics, family interactions, and social climate. The medical
      abnormalities present in individuals with eating disorders are due to starvation
      conditions and purging behaviors and will resolve with nutritional rehabilitation
      and the cessation of purging. Comorbid psychiatric conditions such as affective
      disorders, anxiety disorders, substance abuse, and personality disorders are
      frequently present. For anorexia nervosa, the most effective strategy is
      multidimensional treatment, consisting of nutritional rehabilitation, medical
      attention, individual cognitive psychotherapy, and family counseling or therapy
      if the patient is younger than age 18 years. For bulimia nervosa, the treatment
      of choice is cognitive-behavioral therapy with directions in a manual for
      therapists. A second choice for treatment is an antidepressant, beginning with
      fluoxetine.

PMID- 12510995
TI  - Nature or nurture: determinants of peak bone mass in females.
AB  - Peak bone strength depends on bone mass, bone size (geometry), and bone material
      properties. Most studies to date have focused on bone mass as assessed with the
      use of dual-energy X-ray absorptiometry, with bone mineral content (BMC) and bone
      mineral density (BMD) being best described. Peak BMC accrual follows by 6 months
      the growth spurt of adolescent females, and there is good evidence for tracking
      of BMD during puberty, indicating genetic influence. The search for genes
      involved in the regulation of peak bone strength has revealed inconsistent
      findings. Weight-bearing exercise during the peripubertal years enhances BMD and
      bone geometry of the axial skeleton, but calcium intake is not predictive of peak
      BMD. Estrogen plays a critical role in the accrual of BMC, and nutrition is an
      important factor in both bone size and BMC.

PMID- 12510996
TI  - Structural hypothalamic defects.

PMID- 12510997
TI  - Defects of pituitary development.

PMID- 12510998
TI  - Molecular mechanisms responsible for combined pituitary hormone deficiency.

PMID- 12510999
TI  - Human growth hormone I gene expression is influenced in a complex haplotype
      dependent fashion by polymorphic variation in both the proximal promoter and the
      locus control region.

PMID- 12511000
TI  - GHRH receptor defects.

PMID- 12511001
TI  - Mutations of the GH gene.

PMID- 12511002
TI  - Syndromes of growth hormone bioinactivity.

PMID- 12511003
TI  - SHOX defects in idiopathic short stature.

PMID- 12511004
TI  - NESTEGG: aims and strategies. Northern European Study of Genes in Growth.

PMID- 12511005
TI  - Physiology of normal growth hormone receptor function.

PMID- 12511006
TI  - Molecular modeling of growth hormone receptor mutations.

PMID- 12511007
TI  - Phenotypic variability in growth hormone insensitivity.

PMID- 12511008
TI  - Growth hormone signal transduction and possible defects in children.

PMID- 12511009
TI  - IGF generation in short stature.

PMID- 12511010
TI  - Molecular physiology of IGF-I expression.

PMID- 12511011
TI  - Gene association studies in small for gestational age infants.

PMID- 12511012
TI  - Pathways.

PMID- 12511013
TI  - How do I score thee? Let me count the ways. Or some different methods of
      categorizing Rorschach responses.
AB  - The controversy over the merit of Exner's (1986) Comprehensive System (CS) has
      unfortunately led to a confusion of the CS with all methods of scoring responses
      to inkblots. Six other widely used Rorschach scoring methods and representative
      examples of the research they have generated are described. Objective tests of
      personality ask participants to acknowledge explicit motives, whereas projective
      tests sample implicit needs participants may not recognize. Projective methods
      provide unique means of studying personality dynamics. The CS, whatever its
      merits and limitations, is but 1 of a number of systems of categorizing Rorschach
      responses.

PMID- 12511014
TI  - Origin and history of the earliest Thematic Apperception Test pictures.
AB  - I present the origin and history of the "Series A" pictures of the Thematic
      Apperception Test (TAT; Murray, 1943/1971). The TAT and its pictures evolved
      during the 1930s and early 1940s. The Series A pictures were probably never a
      distinct, fixed set of cards as the name seems to imply. The pictures used were
      in a constant state of flux with additions, deletions, and modifications common.
      In this article I describe the origins of the test and catalog its earliest
      pictures. It is hoped that familiarity with the test's development will increase
      appreciation for the efforts of the test's originators and add perspective and
      depth to one's awareness of the stimuli used.

PMID- 12511015
TI  - Interpersonal personality measures show circumplex structure based on new
      psychometric criteria.
AB  - The importance of the interpersonal circle in organizing the interpersonal domain
      is complemented by its empirical relations with broader personality taxonomies
      and with more specific personality variables. Yet circumplex structure in
      interpersonal measures has often been investigated using the "eyeball test"
      rather than using circumplex criteria of known effectiveness. Simulations (Acton,
      1999) showed the effectiveness of 5 exploratory criteria (3 entirely new) that
      assess the properties of equal spacing, constant radius, and no preferred
      rotation. Along with Browne's (1992) criterion, these were applied to the
      Interpersonal Checklist (ICL; LaForge & Suczek, 1955; N = 763), Interpersonal
      Adjective Scales (IAS; Wiggins, 1979; Ns = 716 and 187), Revised IAS (IAS-R;
      Wiggins, Trapnell, & Phillips, 1988; N = 474), Inventory of Interpersonal
      Problems Circumplex Scales (IIP-C; Alden, Wiggins, & Pincus, 1990; Ns = 616 and
      1,381), and Inventory of Interpersonal Goals (IIG; Horowitz, Dryer, &
      Krasnoperova, 1997; N = 318). In corroboration of interpersonal theory, all
      showed circumplex structure.

PMID- 12511016
TI  - The core of loneliness: lack of pleasurable engagement--more so than painful
      disconnection--predicts social impairment, depression onset, and recovery from
      depressive disorders among adolescents.
AB  - Following past work, we proposed that loneliness possesses a bidimensional
      structure, with dimensions corresponding to lack of pleasurable engagement and
      painful disconnection. Moreover, we hypothesized that the distinction between
      lack of pleasurable engagement and painful disconnection would emerge in
      confirmatory factor analyses, in the pattern of relations of each facet to social
      impairment, in differential risk for the development of depressive disorders, and
      in differential rates of recovery from depressive disorders. Data from the Oregon
      Adolescent Depression Project were used to address these issues. Adolescents from
      high schools in urban and rural Oregon completed interviews and questionnaires on
      psychiatric status, loneliness, social functioning, and so forth, at one point in
      time and then again at a second session approximately a year later. Consistent
      with predictions, we found that the proposed bidimensional structure of
      loneliness represented a good fit to the covariance structure of loneliness
      items; the relation of lack of pleasurable engagement to social impairment
      exceeded that between painful disconnection and social impairment; and lack of
      pleasurable engagement, but not painful disconnection, was significantly related
      (in the expected directions) to onset of and recovery from depressive disorders.
      We discuss theoretical and clinical implications.

PMID- 12511017
TI  - Measuring Chinese psychological well-being with Western developed instruments.
AB  - We explored the possibility of applying 4 psychological scales developed and
      commonly used in the West to Chinese culture. The participants, 273 Chinese and
      302 Americans, completed measures of self-esteem (Self-Esteem Scale; Rosenberg,
      1965), depression (Center for Epidemiologic Studies-Depression Scale; Radloff,
      1977), social support (Multidimensional Scale of Perceived Social Support; Zimet,
      Dahlem, Zimet, & Farley, 1988), and suicidal ideation (Scale for Suicide
      Ideation; Beck, Kovacs, & Weissman, 1979). All scales were found to be reliable
      and valid cross culturally. Comparative analyses suggest that gender differences
      on all 4 scales are smaller among the Chinese than the Americans. Americans were
      more likely to score higher on the socially desirable scales (self-esteem and
      social support) and lower on the socially undesirable scale (suicidal ideation).
      However, no cultural differences were found in this study on the measure of
      depression. Results suggest that, with a few considerations or potential
      modifications, the current measures could be used in Chinese culture.

PMID- 12511018
TI  - The Positive and Negative Suicide Ideation (PANSI) inventory: psychometric
      evaluation with adolescent psychiatric inpatient samples.
AB  - In this study, we evaluated the factor structure of the Positive and Negative
      Suicide Ideation (PANSI) Inventory (Osman, Gutierrez, Kopper, Barrios, & Chiros,
      1998) using confirmatory factor analysis (CFA). The PANSI assesses the frequency
      of negative risk and protective factors that are related to suicidal behavior.
      Participants (n = 195) were adolescent psychiatric inpatients, ages 14 to 17
      years, in the CFA. Results of the CFA supported the fit for the 2-factor oblique
      model as the best fitting model. The internal consistency reliability estimates
      of the 2 subscales, the PANSI-Negative (alpha = .96) and the PANSI-Positive
      (alpha = .89) were high. Scores on the PANSI scales differentiated between
      suicide attempters and controls and those at severe risk for suicide and
      controls. Correlational analyses provide strong support for the concurrent
      validity of the scales. The results of the logistic regression analyses provide
      support for the use of this new inventory as a risk measure of suicide-related
      behaviors: Scores on the PANSI scales (n = 54) also showed satisfactory evidence
      for test-retest reliability over a 2-week period.

PMID- 12511019
TI  - The Infrequency-Posttraumatic Stress Disorder scale (Fptsd) for the MMPI-2:
      development and initial validation with veterans presenting with combat-related
      PTSD.
AB  - Researchers have identified difficulties associated with the use of traditional
      Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom,
      Graham, Tellegen, & Kaemmer, 1989) validity scales with survivors of traumatic
      events. A new scale, the Infrequency-Posttraumatic Stress Disorder scale (Fptsd),
      was created from MMPI-2 items that were infrequently endorsed by 940 male combat
      veterans presenting for treatment at the posttraumatic stress disorder (PTSD)
      clinics of 2 Veterans Affairs Medical Centers. A variety of statistical methods
      were implemented that preliminarily established Fptsd's validity with a
      validation sample of 323 additional PTSD-diagnosed combat veterans. Results
      indicate that, relative to previously established validity and overreporting
      scales (F, Fb, and Fp), Fptsd was significantly less related to psychopathology
      and distress and better at discriminating simulated from genuinely reported PTSD.
      Clinical implications are discussed concerning the use of Fptsd to assess
      disability-seeking veterans suspected of overreporting PTSD symptoms.

PMID- 12511020
TI  - Construct validity of the Life Orientation Test.
AB  - The Life Orientation Test (LOT; Scheier & Carver, 1985) is a common measure of
      optimism. Previous studies of the convergent and discriminant (vis-a-vis
      neuroticism) validity of the LOT have relied solely on questionnaires. Our Study
      1 was a multitrait, multimethod investigation of the LOT incorporating Gottschalk
      and Gleser's (1969) method of content analysis of speech samples as a
      nonquestionnaire assessment method. The LOT did not correlate significantly with
      the Gottschalk Hope Scale (Gottschalk, 1974) derived from speech samples. Study 2
      was an initial attempt to determine the nature of the differences between these
      alternate measures of optimism. In particular, it was hypothesized and found that
      the LOT was more fakable than the Hope Scale. Participants who received special
      instructions to "fake good" scored significantly higher on the LOT than did
      control participants who received no special instructions. Faking instructions
      did not significantly affect scores on the Hope Scale.

PMID- 12511021
TI  - Diagnostic accuracy and factor structure of the AAS and APS scales of the MMPI-2.
AB  - Receiver operating characteristics analysis and sensitivity analysis were used to
      compare the diagnostic accuracy of the Addiction Acknowledgement Scale (AAS;
      Weed, Butcher, McKenna, & Ben-Porath, 1992) and Addiction Potential Scale (APS;
      Weed et al., 1992) of the Minnesota Multiphasic Personality Inventory-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) to that of the MacAndrew Alcoholism
      Scale-Revised (Butcher et al, 1989), the CAGE (Mayfield, McLeod, & Hall, 1974),
      and Svanum's scale (Svanum & McGrew, 1995) in a sample of 338 university
      students. The AAS was the most accurate of these 5 scales at identifying current
      alcohol dependence (as measured by a structured diagnostic interview) and appears
      to offer considerable promise as an alcohol screening instrument. In contrast,
      the APS performed the most poorly of the 5 scales being evaluated, yielding
      results that would be of minimal clinical utility. Factor analysis yielded a 2
      factor solution for the AAS (Acknowledgement of Alcohol/Drug Problems; Positive
      Alcohol Expectancies) and a 4-factor solution for the APS (Satisfaction with
      Self; Cynicism/Pessimism; Impulsivity; Risk-Taking).

PMID- 12511022
TI  - Substance or style? An investigation of the NEO-PI-R validity scales.
AB  - The Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992b) has been
      criticized for the absence of validity scales designed to detect response
      distortion. Recently, validity scales were developed from the items of the NEO-PI
      R (Schinka, Kinder, & Kremer, 1997) and several studies have used a variety of
      methods to test their use. However, it is controversial whether these scales are
      measuring something that is substantive (such as psychopathology or its absence)
      or stylistic (which might be effortful distortion or less conscious processes
      such as lack of insight). In this study, we used a multimethod-multitrait
      approach to examine the validity of these scales in a clinical sample of 668
      participants diagnosed with personality disorders or major depression. Using
      various indicators of both stylistic and substantive variance, confirmatory
      factor analyses (CFA) suggested that these validity scales measure something that
      may be conceptually distinct from, yet highly related to, substantive variance in
      responding.

PMID- 12511023
TI  - GIGANTEA and SPINDLY genes linked to the clock pathway that controls circadian
      characteristics of transpiration in Arabidopsis.
AB  - Several "clock" genes that regulate the circadian system in Arabidopsis thaliana
      have been identified. The GIGANTEA (GI) gene has been shown to participate in the
      circadian system that is linked to overt rhythms in gene expression, leaf
      movements, hypocotyl elongation, and photoperiodic control of flowering in
      Arabidopsis. During continuous light (LL), circadian expression patterns in gi-2
      mutants show reduced amplitudes and altered period lengths when compared with
      controls. Rhythms in stomatal function, such as transpiration, have been shown to
      be endogenous and persist in constant lighting conditions. In order to test for a
      physiologic variable that might be affected by the circadian clock via the GI
      gene, we compared circadian characteristics of transpiration between three
      Arabidopsis mutants (gi-2, spy-4, spy-4/gi-2) and wild-type (WT) controls in
      synchronized (LD for 2.5d) and free-running (LL for 3d) conditions. Each genotype
      showed a significant circadian rhythm in LD at p < 0.001, with acrophases located
      near the middle of the daily 14h L-span, with average amplitudes for WT: 18.9%,
      gi-2: 16.1%, spy-4: 7.7%, and spy-4/gi-2: 5.3%. On the first day in LL, the
      circadian amplitude was dramatically reduced to 3.1% for gi-2 compared with WT
      (11.9%), while amplitudes for spy-4 (6.9%) and spy-4/gi-2 (5.7%) were not
      significantly changed from LD. The amplitude for gi-2 remained low during days 2
      (4.2%) and 3 (2.1%) in LL, while it slowly dampened for the WT (8.6 and 6.6%).
      The amplitudes for spy-4 (6.6%) and spy-4/gi-2 (5.6%) on day 2 in LL were
      indistinguishable from the LD span, but finally dampened on day 3 in LL (1.9 and
      2.3%, respectively). These data suggest that transpiration is a physiologic
      variable controlled by a circadian system that involves both the GI and SPY
      proteins.

PMID- 12511024
TI  - The period gene of the German cockroach and its novel linking power between
      vertebrate and invertebrate.
AB  - Circadian clock protein PERIOD (PER) is essential for the endogenous clockworks
      in diverse lineages within Metazoa, but the protein sequences, the clock protein
      interactions, and the photic responses are variant and different between
      vertebrate and invertebrate PER homologs. Here we identified the German cockroach
      PER homologs and found it could bridge the huge phylogenetic gap and make
      possible a more precise protein sequence comparison between vertebrate and
      invertebrate PER homologs. Seven blocks of conserved regions (c1-c7) interspersed
      within PER proteins were defined, and two new significant homologies were found
      in the upstream portion of c3 region and in the c7 region, respectively. In
      addition, we found all dipteran insects PER homologs lack the c7 region and its
      following amino acid residues. Our results not only reveal the homology and
      divergence, but also imply the constraint and plasticity of divergent PER
      proteins during the course of evolution. These findings lay a solid foundation
      for understanding the general and divergent properties of circadian clockworks in
      diverse lineages within Metazoa.

PMID- 12511025
TI  - Temperature dependent eclosion rhythmicity in the high altitude Himalayan strains
      of Drosophila ananassae.
AB  - The circadian pacemaker controlling the eclosion rhythm of the high altitude
      Himalayan strains of Drosophila ananassae captured at Badrinath (5123 m) required
      ambient temperature at 21 degrees C for the entrainment and free-running
      processes. At this temperature, their eclosion rhythms entrained to 12h light,
      12h dark (LD 12:12) cycles and free-ran when transferred from constant light (LL)
      to constant darkness (DD) or upon transfer to constant temperature at 21 degrees
      C following entrainment to temperature cycles in DD. These strains, however, were
      arrhythmic at 13 or 17 degrees C under identical experimental conditions.
      Eclosion medians always occurred in the thermophase of temperature cycles whether
      they were imposed in LL or DD; or whether the thermophase coincided with the
      photophase or scotophase of the concurrent LD 12:12 cycles. The temperature
      dependent rhythmicity in the Himalayan strains of D. ananassae is a rare
      phenotypic plasticity that might have been acquired through natural selection by
      accentuating the coupling sensing mechanism of the pacemaker to temperature,
      while simultaneously suppressing the effects of light on the pacemaker.

PMID- 12511026
TI  - The hamster clock phase-response curve from summerlike light:dark cycles and its
      role in daily and seasonal timekeeping.
AB  - We address the subject of entrainment of the hamster clock by the day:night cycle
      in summer when the sun sets after 6 PM and rises before 6 AM (nights < 12 h).
      Summer day:night cycles were simulated by 6 light:dark (LD) cycles with D < 12 h
      (summerlike, SLD) ranging from SLD 12.5 h:11.5 h (D, 6:15 PM-5:45 AM) to 18 h:6 h
      (D, 9 PM-3 AM). These are the near limiting SLDs for constant PM timing
      (entrainment) of behavioral estrus and wheel running in hamsters. The onset of
      estrus was observed every 4 d in the same hamsters as a phase marker of their 24
      h clock. On the day before an experimental estrus, preceded and followed by
      control onsets, a dark period was imposed to cover a putative 6 PM-6 AM light
      sensitive period (LSP). This was scanned with a light pulse (and periodic 5 sec
      bell alarms) lasting 5-240 min. Shifts in onset of estrus on the next day were
      plotted vs. the end of the light pulse for PM times ("dusk") and its onset for AM
      times ("dawn"). The resulting phase shifts from the six SLDs were similar,
      permitting their combination into a single phase-response curve (PRC) of 1605
      shifts. This SLD composite PRC rose at 10:15 PM, peaked at 2 AM (81 min advanced
      shift), fell linearly to 5:55 AM, and then abruptly to normal at 6 AM (no shift).
      Peak shift was unaffected by light pulse duration or intensity, or hamster age.
      The SLD composite PRC lacked the 6 PM-9 PM curve of delayed shifts present in
      reported PRCs from LD 12 h:12 h and DD. However, a two-pulse experiment showed
      that all light from 6 PM to L-off was needed to block (balance) the advancing
      action of a 5 min morning light pulse, thereby maintaining entrainment. A working
      hypothesis to explain daily entrainment and seasonal fertility in the golden
      hamster is illustrated. A nomenclature for labeling the phases of the hamster
      clock (circadian time) is proposed.

PMID- 12511027
TI  - Rats made cirrhotic by chronic CCl4 treatment still exhibit anticipatory activity
      to a restricted feeding schedule.
AB  - Food entrainment of clock genes in the liver suggests that this organ may
      underlie a food entrained oscillator (FEO), which manifests under restricted
      feeding schedule (RFS). In order to test the importance of a functional liver for
      the expression of FEO, chronic CCl4-treated cirrhotic rats and oil-treated
      controls were entrained to RFS and drinking behavior was continuously monitored.
      After 20 d of free-running conditions, food access was restricted to 2 h,
      followed by a refeeding-fasting protocol to test persistence of anticipatory
      drinking. Present data show no differences between groups for the onset and
      intensity of anticipation during RFS. After RFS, however, cirrhotic rats
      exhibited a significantly longer free-running period and a delay and lower
      intensity of the persistence of activity under fasting conditions. Histology
      confirmed injury of the liver chronically treated with CCl4. Present data
      indicate that a dysfunctional liver due to chronic CCl4 does not prevent animals
      from exhibiting anticipatory activity but may promote metabolic derangement of
      the clock mechanisms of the suprachiasmatic nucleus and the FEO.

PMID- 12511028
TI  - Right- and left-brain hemisphere. Rhythm in reaction time to light signals is
      task-load-dependent: age, gender, and handgrip strength rhythm comparisons.
AB  - In healthy mature subjects simple reaction time (SRT) to a single light signal
      (an easy task) is associated with a prominent rhythm with tau = 24 h of dominant
      (DH) as well as nondominant (NDH) hand performance, while three-choice reaction
      time (CRT), a complex task, is associated with tau = 24 h of the DH but tau < 24
      h of the NDH. The aims of the study were to assess the influence of age and
      gender on the difference in tau of the NDH and DH, as it relates to the
      corresponding cortical hemisphere of the brain, in comparison to the rhythm in
      handgrip strength. Healthy subjects, 9 (5 M and 4 F) adolescents 10-16 yr of age
      and 15 (8 M and 7 F) adults 18-67 yr of age, active between 08:00 +/- 1 h and
      23:00 +/- 1:30 h and free of alcohol, tobacco, and drug consumption volunteered.
      Data were gathered longitudinally at home and work 4-7 times daily for 11-20 d.
      At each test time the following variables were assessed: grip strength of both
      hands (Dynamometer: Colin-Gentile, Paris, France); single reaction time to a
      yellow signal (SRT); and CRT to randomized yellow, red, or green signal series
      with varying instruction from test to test (Psycholog-24: Biophyderm, France).
      Rhythms in the performance in SRT, CRT, and handgrip strength of both DH and NDH
      were explored. The sleep-wake rhythm was assessed by sleep-logs, and in a subset
      of 14 subjects it was also assessed by wrist actigraphy (Mini-Motionlogger: AMI,
      Ardsley NY). Exploration of the prominent period tau of time series was achieved
      by a special power spectra analysis for unequally spaced data. Cosinor analysis
      was used to quantify the rhythm amplitude A and rhythm-adjusted mean M of the
      power spectral analysis determined trial tau. A 24h sleep-wake rhythm was
      detected in almost all cases. In adults, a prominent tau of 24 h characterized
      the performance of the easy task by both the DH and NDH. In adults a prominent
      tau of 24 h was also detected in the complex CRT task performed by the DH, but
      for the NDH the tau was < 24 h. This phenomenon was not gender-related but was
      age-related since it was seldom observed in adolescent subjects. Hand-side
      differences in the grip strength rhythms in the same individuals were detected,
      the tau being ultradian rather than circadian in adolescent subjects while in
      mature subjects the tau frequently differed from that of the rhythm in CRT. These
      findings further support the hypothesis that functional biological clocks exist
      in both the left and right hemispheres of the human cortex.

PMID- 12511029
TI  - Circadian rhythms of oviposition and feeding activity in Japanese quail: effects
      of cyclic administration of melatonin.
AB  - The aim of these experiments was to test the effect of a cyclic administration of
      melatonin, by mimicking the daily rhythm of hormone levels, on the circadian
      organization of two distinct functions in quail: oviposition and feeding
      activity. Laying and feeding rhythms under photoperiodic conditions and constant
      darkness (DD) were investigated. Under DD, where the two rhythms were free
      running, a daily rhythm of melatonin was administered. In LD 14 h:10 h, two
      different individual profiles of laying were established, with stable females
      laying at the same time each day and delayed females laying progressively later
      each day. For feeding activity, all birds were clearly synchronized to the
      photoperiodic cycle. In DD, the laying birds showed a free-running rhythm of
      oviposition with a period longer than 24 h for both profiles but the delayed
      profile females had a longer period than stable profile females. In comparison,
      the free-running period of feeding rhythm of the same birds was shorter than 24
      h. A cyclic administration of melatonin had no effect on laying rhythm, which
      continued to free-run in DD, whereas feeding activity was synchronized as soon as
      the first cycle of melatonin was administered. From these results, it seems that
      two different circadian systems drive each of the two types of behavior
      separately. Melatonin could be the main synchronizer for the temporal control of
      feeding behavior, but it does not play a part in the control of oviposition in
      Japanese quail.

PMID- 12511030
TI  - Pharmacological blockage of serotonin biosynthesis and circadian changes in
      oxaliplatin toxicity in rats.
AB  - This study investigates if the serotoninergic system plays a role in chronotoxic
      effects of the anticancer agent oxaliplatin (l-OHP). Four groups of female rats
      (120 in total) synchronized with light-dark (12 h:12 h) were treated with: (i)
      saline, (ii) para-chlorophenylalanine (pCPA, an inhibitor of serotonin
      biosynthesis: 300 mg/kg/d, i.p. for two consecutive days), (iii) l-OHP (23 mg/kg,
      i.v.) at three different dosing times, or (iv) both pCPA and l-OHP. The results
      show pCPA (ii) obliterates the circadian rhythm in plasma ACTH but not in
      corticosterone or leukocytes, and (iii) l-OHP exerts circadian time-dependent
      toxic effects (body weight loss, leukopenia, and intestinal lesions) with
      greatest toxicity coinciding with treatment at the end of the nocturnal activity
      span (P < 0.05). In rats whose serotonin biosynthesis was blocked (iv), the
      circadian rhythms in the toxic effects of l-OHP and in ACTH were obliterated,
      while the rhythms in corticosterone and leukocytes persisted.

PMID- 12511031
TI  - Circadian rhythms during cycling exercise and finger-tapping task.
AB  - The aim of this study was to follow the circadian fluctuation of the spontaneous
      pedal rate and the motor spontaneous tempo (MST) in a sample of highly trained
      cyclists. Ten subjects performed five test sessions at various times of day.
      During each test session, subjects were required to perform (i) a finger-tapping
      task, in order to set the MST and (ii) a submaximal exercise on a cycle ergometer
      for 15 min at 50% of their Wmax. For this exercise, pedal rate was freely chosen.
      Spontaneous pedal rate and heart rate (HR) were measured continuously. The
      results demonstrated a circadian variation for mean oral temperature, HR, and
      MST. Under submaximal exercise conditions, HR showed no significant time-of-day
      influence although spontaneous pedal rate changed significantly throughout the
      day. Circadian rhythm of oral temperature and pedal rate were strongly
      correlated. Moreover, a significant positive correlation was found between MST
      and pedal rate. Both parameters may be controlled by a common brain oscillator.
      MST, rest HR, and pedal rate changes follow the rhythm of internal temperature,
      which is considered to be the major marker in chronobiology, therefore, if there
      is a relation between MST and pedal rate, we cannot rule out partial dependence
      of both parameters on body temperature.

PMID- 12511032
TI  - Mood and the circadian system: investigation of a circadian component in positive
      affect.
AB  - The aim of this study was to test if the pattern of human mood variation across
      the day is consistent with the hypothesis that self-reports of positive affect
      (PA) have a circadian component, and self-reports of negative affect (NA) do not.
      Data were collected under two protocols: normal ambulatory conditions of activity
      and rest and during a 27 h constant routine (CR) procedure. Mood data were
      collected every 3 h during the wake span of the ambulatory protocol and hourly
      during the 27 h CR. In both protocols, rectal temperature data were continuously
      recorded. In the ambulatory protocol, activity data were also collected to enable
      estimation of the unmasked (purified) temperature rhythm. Participants were 14
      healthy females aged 18-25 yr in the follicular phase of the menstrual cycle.
      Under both protocols, PA exhibited significant 24 h temporal variation [CR: F(23,
      161) = 2.12, p < 0.01; ambulatory: F(5,55) = 2.44, p < 0.05] with a significant
      sinusoidal component [CR: F(2, 21) = 7.51, p < 0.01; ambulatory: F(2,3) = 20.49,
      p < .05] of the same form as the circadian temperature rhythm. In contrast, NA
      exhibited an increasing linear trend over time under the ambulatory protocol
      [F(1, 11) = 5.74, p < 0.05] but nonsignificant temporal variation under the CR
      protocol. The findings support the hypothesis of a circadian component in PA
      variation.

PMID- 12511033
TI  - Aging and the circadian rhythm of melatonin: a cross-sectional study of Chinese
      subjects 30-110 yr of age.
AB  - Although previous reports indicate that nocturnal plasma melatonin secretion
      declines with age, some recent findings do not support this point. In the present
      cross-sectional study, we documented serum melatonin concentrations at two time
      points, 02:00 and 08:00 h, in 144 persons aged 30-110 yr and found a significant
      age-related decline. It began around the age of 60 and reached a very
      significantly lower level in subjects in their 70s and over 80 yr of age (P <
      0.01, when compared with age <60 yr). Nocturnal melatonin levels were higher
      among (post-menopausal only) women than men overall (P < 0.05). In the older age
      groups, nocturnal melatonin levels did not differ between healthy controls and
      subjects with high blood pressure or ischemic heart disease. To further check
      these results, we also assessed the circadian pattern of serum melatonin in four
      subgroups of healthy men, aged 30-39, 40-49, 50-59, and 60-69 yr: blood samples
      were taken at 2 h intervals from 08:00 to 22:00 h and hourly from 22:00 to 08:00
      h. Our results showed generally similar circadian melatonin patterns that peaked
      at night with very low levels during the daytime. No significant difference was
      found among the three younger groups, but nocturnal melatonin levels were
      significantly lower in the men in their 60s.

PMID- 12511034
TI  - The tolerance-hyperbaric test: a chronobiologic approach for improved diagnosis
      of hypertension.
AB  - Blood pressure (BP) displays predictable large-amplitude circadian variability.
      Thus, the identification and the proper definition of hypertension are highly
      ambiguous when based on single time-unspecified measurements. One way to deal
      with such variability in the diagnosis of hypertension is to replace the commonly
      used constant limits of BP by a time-specified reference interval based on the
      normal circadian BP rhythm assessed by ambulatory BP monitoring (ABPM). A proper
      reference limit can be constructed, for instance, as a tolerance interval
      computed for every specific time interval throughout the 24 h. Once such a
      threshold (given by the upper limit of the tolerance interval) is constructed, a
      hyperbaric index (HBI) can be computed by numerical integration of the total area
      of any given patient's BP profile above threshold. The HBI plus the duration of
      excess within the 24h day serves as nonparametric endpoints for assessing
      hypertension. Both retrospective and prospective evaluation of this tolerance
      hyperbaric test validate its high sensitivity and specificity in the diagnosis of
      hypertension. We describe the theory of the HBI as well as a newly created
      dedicated software program that automatically derives the tolerance intervals
      from a reference database of normotensive subjects and calculates the HBI and
      other potentially valuable parameters based on data obtained by ABPM. The
      establishment of time-qualified tolerance limits and the assessment of the extent
      and timing of BP elevation represents a valuable tool for the more accurate
      diagnosis of hypertension as well as means of gauging response to treatment.

PMID- 12511035
TI  - A history of ultraviolet photobiology for humans, animals and microorganisms.

PMID- 12511036
TI  - Introduction to the symposium-in-print: photoisomerization pathways, torsional
      relaxation and the hula twists.
AB  - A review of recent literature on volume-conserving cis-trans photoisomerization
      reaction mechanism, including hula twist, is presented. Differences between
      substrates trapped in amorphous solids and chromophores that are protein bound
      are discussed.

PMID- 12511037
TI  - Mechanistic pathways for the photoisomerization reaction of the anchored,
      tethered chromophore of the photoactive yellow protein and its mutants.
AB  - We show by way of physical organic reasoning that the currently known
      photochemical results of the chromophore of photoactive yellow protein (PYP) are
      consistent with that expected of a least volume-demanding process for an
      anchored, tethered chromophore. The primary photoreaction, interestingly, does
      not appear to involve a hula-twist process. However, the latter might be involved
      during subsequent transition of dark intermediates. Absorption data of
      intermediates obtained from a microsecond time-resolved spectroscopic study of
      three PYP mutants (E46Q, T50V and R52Q) are consistent with the above analyses.

PMID- 12511038
TI  - Hula-twist within the confinement of molecular crystals.
AB  - E/Z-photoisomerizations within molecular crystals are varied. Existing cases are
      summarized. They require crystal lattices that allow for long-range molecular
      movements in the nontopotactic solid-state mechanism. Reactivity and
      directionality can be foreseen on the basis of the crystal packing. The reacting
      crystal changes continuously by phase rebuilding, phase transformation and
      disintegration. Two possibilities for the chemical mechanism exist: (1) highly
      space-demanding (cooperative) double-bond rotations; and (2) space-conserving
      hula-twist (HT) motions while the substituents move within their planes and only
      one C-H unit undergoes out-of-plane translocation. If internal rotation cannot be
      reasonably modeled within the crystal lattice, HT remains the only choice, as in
      the case of trans-1,2-dibenzoylethene. Direct experimental proof is still lacking
      because the differences in the conformational outcome could not be assessed in
      the studied examples. Density functional theory calculations of cis-1,2
      dibenzoylethene revealed very low differences in energy content of the helical (s
      cis, s-cis)- and the almost orthogonal (s-cis, s-trans)-cis-conformers. The
      almost orthogonal (s-cis, s-trans)-cis-conformer that is found in the pure
      crystal is very similar to the calculated counterpart. It is suggested that more
      favorable initial conformers might be obtained by proper vinylic substitution.
      The stereochemical outcome of highly space-demanding thermal vinylic-bond
      rotations followed by cyclizations of conjugated bisallenes to give bismethylene
      cyclobutenes excludes the alternative HT mechanism (double-bond isomerization) in
      the present cases. But space-conserving HT might be a mechanistic alternative in
      less-substituted cases under photoexcitation. The stereochemical consequences are
      discussed.

PMID- 12511039
TI  - Photoisomerization of stilbene dendrimers: the need for a volume-conserving
      isomerization mechanisms.
AB  - Highly branched stilbene dendrimers were synthesized and their photochemical
      behavior was studied. Even the stilbene dendrimer with molecular weight over 6500
      underwent trans-cis isomerization in the excited singlet state within the
      lifetime of 10 ns. The photoisomerization of C=C double bond of stilbene
      dendrimers in the excited state may proceed by a volume-conserving novel
      mechanism such as hula-twist rather than conventional 180 degrees rotation around
      the C=C double bond based on fluorescence and isomerization experiments.

PMID- 12511040
TI  - Constraints of opsin structure on the ligand-binding site: studies with ring
      fused retinals.
AB  - Ring-fused retinal analogs were designed to examine the hula-twist mode of the
      photoisomerization of the 9-cis retinylidene chromophore. Two 9-cis retinal
      analogs, the C11-C13 five-membered ring-fused and the C12-C14 five-membered ring
      fused retinal derivatives, formed the pigments with opsin. The C11-C13 ring-fused
      analog was isomerized to a relaxed all-trans chromophore (lambda(max) > 400 nm)
      at even -269 degrees C and the Schiff base was kept protonated at 0 degrees C.
      The C12-C14 ring-fused analog was converted photochemically to a bathorhodopsin
      like chromophore (lambda(max) = 583 nm) at -196 degrees C, which was further
      converted to the deprotonated Schiff base at 0 degrees C. The model-building
      study suggested that the analogs do not form pigments in the retinal-binding site
      of rhodopsin but form pigments with opsin structures, which have larger binding
      space generated by the movement of transmembrane helices. The molecular dynamics
      simulation of the isomerization of the analog chromophores provided a twisted C11
      C12 double bond for the C12-C14 ring-fused analog and all relaxed double bonds
      with a highly twisted C10-C11 bond for the C11-C13 ring-fused analog. The
      structural model of the C11-C13 ring-fused analog chromophore showed a
      characteristic flip of the cyclohexenyl moiety toward transmembrane segments 3
      and 4. The structural models suggested that hula twist is a primary process for
      the photoisomerization of the analog chromophores.

PMID- 12511041
TI  - H-vinyl conical intersections for dienes: a mechanism for the photochemical hula
      twists.
AB  - The potential role of "H-vinyl" conical intersections in a photochemical process
      known as the hula twist has been evaluated. The H-vinyl conical intersections of
      butadiene are explored with complete active space self-consistent field
      calculations, and proposals about the geometries involved in the hula-twist
      mechanism are discussed and contrasted with the conventional one-bond flip
      mechanism of cis-trans isomerization.

PMID- 12511042
TI  - Structure of the conical intersections driving the cis-trans photoisomerization
      of conjugated molecules.
AB  - High-level ab initio calculations show that the singlet photochemical cis-trans
      isomerization of organic molecules under isolated conditions can occur according
      to two distinct mechanisms. These mechanisms are characterized by the different
      structures of the conical intersection funnels controlling photoproduct
      formation. In nonpolar (e.g. hydrocarbon) polyenes the lowest-lying funnel
      corresponds to a (CH)3 kink with both double and adjacent single bonds twisted,
      which may initiate hula-twist (HT) isomerization. On the other hand, in polar
      conjugated systems such as protonated Schiff bases (PSB) the funnel shows a
      structure with just one twisted double bond. The ground-state relaxation paths
      departing from the funnels indicate that the HT motion may take place in nonpolar
      conjugated systems but also that the single-bond twist may be turned back,
      whereas in free conjugated polar molecules such as PSB a one-bond flip mechanism
      dominates from the beginning. The available experimental evidence either supports
      these predictions or is at least consistent with them.

PMID- 12511043
TI  - The low-temperature photochemistry of s-cis acyclic 1,3-dienes.
AB  - In this article we have examined the very low-temperature photochemistry of three
      acyclic 1,3-dienes. We have used high-temperature deposition techniques combined
      with matrix isolation to create samples enriched with the thermally meta-stable s
      cis form. This technique has allowed us to examine the separate photochemistry of
      the s-cis and s-trans conformers. Our results suggest the presence and the
      absence of barriers on the excited-state surface. In particular, we have found
      that the electrocyclic closure and s-cis-s-trans photochemical isomerization
      stops at 15 K for 2,3-dimethyl-1,3-butadiene-d10. The closure occurs at higher
      temperatures in solution but is slowed by a deuterium isotope effect. The s-trans
      conformer of EE-2,4-hexadiene shows almost no photoreactivity in a matrix under
      254 nm irradiation, but the s-cis conformer is rapidly converted to ZE-2,4
      hexadiene (ZE-HXD). The photoreactivity of ZE-HXD is similar in that there is a
      relatively quick conversion of the s-cis conformer under these conditions, with
      only a very slow conversion of the s-trans to photoproducts.

PMID- 12511044
TI  - Ultraviolet-B-induced inactivation of human OGG1, the repair enzyme for removal
      of 8-oxoguanine in DNA.
AB  - The OGG1 proteins are DNA N-glycosylases-apurinic-apyrimidinic lyases that are
      responsible for the removal of 8-oxo-7,8-dihydroguanine (8-oxoG) base in DNA. The
      human enzyme (hOGG1) is a monomer of 345 amino acids containing 10 buried
      tryptophan (Trp) residues that are very sensitive to UVB irradiation. The
      photolysis quantum yield of these Trp residues is about 0.3 and 0.1 in argon- and
      air-saturated solutions, respectively. Matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry shows that several cleavage sites are
      identical under aerobic and anaerobic photolysis of Trp residues; one of them
      includes the active site. Western blots and polyacrylamide gel electrophoresis
      indicate that fragments of high molecular size are also formed. In addition to
      common photochemical paths with argon-saturated solutions, specific reactions
      occur in air-saturated solutions of hOGG1. The photolysis rate is inhibited by
      more than 50% on binding of hOGG1 to a 34mer oligonucleotide containing a single
      8-oxoG-C base pair. Binding to the oligonucleotide with 8-oxoG-C induced a 20%
      quenching of the hOGG1 fluorescence, suggesting interaction of nucleic acid bases
      with the Trp residue(s) responsible for the photolysis. Using 2,6-diamino-4
      hydroxy-5-N-methylformamidopyrimidine (Me-FapyG) and 8-oxoG as substrates, it is
      shown that protein photolysis induces photoinactivation of the DNA N-glycosylase
      activities. The excision of 8-oxoG is more affected than that of Me-FapyG at the
      same dose of UVB irradiation under both air and argon conditions. Besides the
      role of Trp residues, the possible involvement of Cys 253 in the
      photoinactivation process of hOGG1 is discussed.

PMID- 12511045
TI  - Photochemically catalyzed reaction of ochratoxin A with D- and L-cysteine.
AB  - The photolysis (>300 nm) of ochratoxin A (OTA, N-[[(3R)-5-chloro-8-hydroxy-3
      methyl-1-oxo-7-isochromanyl]carbonyl]-3-phenyl-L-alanine, 1) in the presence of
      excess (2 and 12 molar equiv) cysteine (CySH) has been investigated and found to
      yield sulfur adducts 5 and 6 that are characterized by liquid chromatography-mass
      spectrometry and 1H-NMR spectroscopy. The adduct 5 was ascribed to the Michael
      addition conjugate resulting from covalent attachment of CySH to the ochratoxin
      quinone (4) generated by photooxidation of OTA. This species was also formed by
      photolysis of a synthetic sample of the hydroquinone of OTA (ochratoxin
      hydroquinone, 3) in the presence of 12 equiv L-CySH. The conjugate 5 derived from
      photolysis of 3 with L-CySH was used for 1H-NMR analysis. The sulfur adduct 6 was
      the major species detected from covalent attachment of CySH to photoactivated
      OTA, and it resulted from direct displacement of the OTA Cl atom by CySH. The
      implications of the cysteinyl adducts to the in vivo toxicity of OTA are
      discussed, with particular emphasis given to conjugate 5, as products from the
      photooxidative pathway may be of relevance to the nephrotoxic properties of OTA.

PMID- 12511046
TI  - Dietary, but not topical, alpha-linolenic acid suppresses UVB-induced skin injury
      in hairless mice when compared with linoleic acids.
AB  - Peroxidizability of fatty acids in the air is roughly proportional to the number
      of double bonds, but in vivo peroxidation proceeds in a more complex manner.
      Here, we compared the effects of dietary and topically applied oils enriched with
      linoleic acid (LA, 18:2n-6) or alpha-linolenic acid (ALA, 18:3n-3) on UV-induced
      skin injury in a strain of hairless mice. The UVB-induced erythema score was
      significantly lower in mice with topically applied creams containing LA and ALA
      than in mice with the basal cream; no significant increase in the score was
      detected in the ALA group compared with the LA group. However, dietary ALA
      inhibited the increase in erythema score after UVB irradiation compared with LA.
      The peroxidizability index of the skin total lipids was significantly higher, but
      UVB-induced prostaglandin E2 (PGE2) production was significantly lower in the
      group fed an ALA-rich diet compared with the group fed an LA-rich diet. The
      levels of thiobarbituric acid-reactive substances, estimated in the presence of
      butylated hydroxytoluene in the assay mixture, were not affected by UVB treatment
      or by the dietary fatty acids, but the severity of the skin lesion was associated
      with PGE2 levels. These results indicate that the type of fatty acids, n-6 or n
      3, is critical for the suppression of UVB-induced skin lesion when the skin fatty
      acids are modified by dietary manipulation. Anti-inflammatory activity of dietary
      flaxseed oil with relatively high ALA and low LA contents was demonstrated in UVB
      irradiated hairless mice.

PMID- 12511047
TI  - Ultraviolet emission spectra of sunbeds.
AB  - It is well known that UV radiation contributes to the development of skin cancer.
      Exposure to solar radiation is predominantly responsible for the high incidence
      rate of skin cancer, but there are also indications that sunbeds are involved.
      The aim of the present investigation was to determine the UV emission spectra of
      sunbeds. It included the most common sunbed models, which cover more than 50% of
      the Swiss market. The UV emission spectra of sunbeds have special characteristics
      and are different from the sun spectrum, which can be seen in high-resolution
      spectral measurements. Sunbed emission spectra are similar to the sun spectrum in
      the UVB (280-320 nm) range but reach values 10 to 15 times higher in the UVA (320
      400 nm) range. An average erythema-effective irradiance of 0.33 W/m2 was
      determined for sunbeds. This corresponds to a UV index of 13, which is
      significantly higher than the UV index of 8.5 of the high summer sun at noon at
      intermediate latitudes. The measurements were spread over the whole effective
      area of the sunbeds, and an inhomogeneous distribution of the irradiances with
      variations of up to 30% from the average value was found.

PMID- 12511048
TI  - UV dose measurements of photosensitive dermatosis patients by polycrystalline GaN
      based portable self-data-acquisition UV monitors.
AB  - We have developed a UV monitor with polycrystalline (poly-) gallium nitride (GaN)
      UV sensors and evaluated its performance from the viewpoint of its effectiveness
      for use with photosensitive dermatosis patients. The poly-GaN UV sensor is
      sensitive to UV light from 280 to 410 nm even without optical filters. The UV
      monitor is a portable self-data-acquisition instrument with a minimum detection
      level (defined as average UV intensity over 290 to 400 nm) of 2 microW/cm2 and
      can store UV dose data for 128 days. It allows easy measurement of four orders of
      magnitude of ambient UV intensity and dose from indoor light to direct solar
      radiation in summer. Trial use of the UV monitor by five xeroderma pigmentosum
      patients started in June 2000 and was carried out for 1 year. It was demonstrated
      that the UV monitor was useful in improving their quality of life.

PMID- 12511049
TI  - Squaraine dyes for photodynamic therapy: study of their cytotoxicity and
      genotoxicity in bacteria and mammalian cells.
AB  - Halogenated squaraine dyes are characterized by long wavelength absorption (>600
      nm) and high triplet yields and therefore represent new types of photosensitizers
      that could be useful for photodynamic therapy. We have analyzed the cytotoxicity
      and genotoxicity of the bromo derivative 1, the iodo derivative 2 and the
      corresponding nonhalogenated dye 3 in the absence and presence of visible light.
      At concentrations of 1-2 microM, 1 and 2 reduced the cloning efficiency of AS52
      Chinese hamster ovary cells to less than 1% under conditions that were well
      tolerated in the dark. Similarly, the proliferation of L5178Y mouse lymphoma
      cells was inhibited by photoexcited 1 and 2 with high selectivity. The squaraine
      3 was much less efficient. Both 1 and 2 induced only few mutations in the gpt
      locus of the AS52 cells in the presence of light and were not mutagenic in the
      dark. No mutagenicity with and without irradiation was observed in Salmonella
      typhimurium TA100 and TA2638. However, both 1 and 2 plus light increased the
      frequency of micronuclei in AS52 cells. The results indicate that halogenated
      squaraines exhibit photobiological properties in vitro that are favorable for
      photodynamic therapeutical applications.

PMID- 12511050
TI  - A comparison of protoporphyrin IX and protoporphyrin IX dimethyl ester as a
      photosensitizer in poorly differentiated human nasopharyngeal carcinoma cells.
AB  - Protoporphyrin IX dimethyl ester (PME), a dimethyl esterification of
      protoporphyrin IX (PpIX), exhibits higher intracellular uptake into NPC/CNE2
      cells, a poorly differentiated human nasopharyngeal carcinoma, than does PpIX.
      Phototoxicity studies reveal PME to be a more potent photosensitizer than is
      PpIX, at the early and late incubation time points. Correlating phototoxicity
      with subcellular localization indicates that PME is a more potent photosensitizer
      when its primary target of photodamage is mitochondria. Also, additional
      targeting of lysosome enhances phototoxicity.

PMID- 12511051
TI  - A beam-splitting device for use with fiber-coupled laser light sources for
      photodynamic therapy.
AB  - A device that divides light into eight, four or two beams of equivalent power
      with only minor total power loss was designed, built and tested. The apparatus
      accepts light from a 200 microm diameter, 0.16 numerical aperture, silica-silica
      multimode optical fiber connected to one of several laser light sources for
      photodynamic therapy (PDT) of cancer. The incorporation of a variable iris
      diaphragm into the optical couplers allows the power of the beams to be
      independently set. Each of the beams can be coupled to a 400 or 600 microm
      diameter optical fiber to deliver the therapeutic light to the patient. This
      device is used in our institute for PDT of patients with either numerous small
      malignant tumors or single tumors with large surface area.

PMID- 12511052
TI  - Internalization of aggregated photosensitizers by tumor cells: subcellular time
      resolved fluorescence spectroscopy on derivatives of pyropheophorbide-a ethers
      and chlorin e6 under femtosecond one- and two-photon excitations.
AB  - Amphiphilic sensitizers self-associate in aqueous environments and form
      aggregated species that exhibit no or only negligible photodynamic activity.
      However, amphiphilic photosensitizers number among the most potent agents of
      photodynamic therapy. The processes by which these sensitizers are internalized
      into tumor cells have yet to be fully elucidated and thus remain the subject of
      debate. In this study the uptake of photosensitizer aggregates into tumor cells
      was examined directly using subcellular time-resolved fluorescence spectroscopy
      with a high temporal resolution (20-30 ps) and high sensitivity (time-correlated
      single-photon counting). The investigations were performed on selected
      sensitizers that exhibit short fluorescence decay times (< 50 ps) in aggregated
      form. Derivatives of pyropheophorbide-a ether and chlorin e6 with varying
      lipophilicity were used for the study. The characteristic fluorescence decay
      times and spectroscopic features of the sensitizer aggregates measured in aqueous
      solution also could be observed in A431 human endothelial carcinoma cells
      administered with these photosensitizers. This shows that tumor cells can
      internalize sensitizers in aggregated form. Uptake of aggregates and their
      monomerization inside cells were demonstrated directly for the first time by
      means of fluorescence lifetime imaging with a high temporal resolution.
      Internalization of the aggregates seems to be endocytosis mediated. The degree of
      their monomerization in tumor cells is strongly influenced by the lipophilicity
      of the compounds.

PMID- 12511053
TI  - Glucose is required to maintain high ATP-levels for the energy-utilizing steps
      during PDT-induced apoptosis.
AB  - Photodynamic therapy (PDT) may trigger apoptosis or necrosis in cancer cells.
      Several steps in the induction and execution of apoptosis require high amounts of
      adenosine-5'-triphosphate (ATP). Because the mitochondrial membrane potential
      (delta psi) decreases early in apoptosis, we raised the question about the
      mechanisms of maintaining a sufficiently high ATP level. We therefore monitored
      delta psi and the intracellular ATP level of apoptotic human epidermoid carcinoma
      cells (A431) after photodynamic treatment with aluminum (III) phthalocyanine
      tetrasulfonate. A maximum of caspase-3-like activity and nuclear fragmentation
      was found at fluences of about 4 J cm(-2). Under these conditions apoptotic cells
      reduced delta psi rapidly, while the ATP level remained high for 4-6 h after
      treatment for cells supplied with glucose. To analyze the contribution of
      glycolysis to the energy supply during apoptosis, experiments were carried out
      with cells deprived of glucose. These cells showed a rapid drop of ATP content
      and neither caspase activation nor nuclear fragmentation could be detected. We
      conclude that the use of glucose as a source of ATP is obligatory for the
      execution of PDT-induced apoptosis.

PMID- 12511054
TI  - Motivational intervention as applied to systems change: the case of dual
      diagnosis.
AB  - The concept of motivational interviewing is based on helping individual clients
      build and sustain a commitment to reach and carry out a decision to change. In
      this paper, the motivational interviewing model is applied to systems change.
      Different stages of involvement and readiness to change are identified within
      systems which closely resemble those found in individuals. When applied to a
      system, we call this process "Motivational Intervention." In this paper, the
      motivational intervention model is applied to a psychiatric system of health care
      delivery where large numbers of psychiatric patients are found to also have
      substance use-related problems. Several Italian health districts invited the
      authors to present a series of lectures and workshops in order to facilitate the
      incorporation of substance user treatment into existing psychiatric services.
      Using the motivational intervention model to determine where the system was in
      the process of change, we then identified the tasks necessary to facilitate
      further change.

PMID- 12511055
TI  - The association of tobacco smoking and depression in adolescence: evidence from
      the United States.
AB  - INTRODUCTION: We examine a suspected causal association between tobacco smoking
      and depression. Using data from the National Household Survey on Drug Abuse
      (NHSDA), we explore variation in depression severity among current and former
      smokers compared to nonsmokers. We focus on the association between time since
      last smoke in former smokers and depression severity, to examine whether the
      level of tobacco-depression relationship might vary in a time-dependent fashion.
      METHODS: Our cross-sectional data come from three public use files of the U.S.
      National Household Survey on Drug Abuse (NHSDA), collected with different
      respondents each year from 1994 to 1996, for participants 12-17 years old (N =
      13,827). Ordinal logistic regression is used to assess the association between
      severity of depression and cigarette smoking among former and current smokers.
      RESULTS: Current smokers had the highest odds for depression, followed by former
      smokers, then nonsmokers. Females had higher odds of depression compared to
      males. The odds of depression varied in subgroups of former smokers. Odds of
      depression were lower with more elapsed time since last smoke. DISCUSSION: We add
      new evidence on depression in association with tobacco smoking. Teens who quit
      smoking may reduce their odds of depressed mood, but more research is needed
      before a definite causal path can be established.

PMID- 12511056
TI  - Drug user treatment referrals and entry among participants of a needle exchange
      program.
AB  - OBJECTIVE: To compare characteristics of needle exchange program (NEP)
      participants who requested methadone treatment to those who did not, compare
      participants who subsequently enrolled into treatment to those who did not
      enroll, and suggest possible barriers to treatment among NEP participants.
      METHODS AND MATERIALS: Between 8/94 and 2/97, data pertaining to demographics and
      drug use were collected from Baltimore NEP participants upon registration.
      Participants were made aware that referrals to off-site methadone maintenance
      were available upon request. Odds ratios and multiple logistic regression models
      were used to compare those who requested treatment to those who did not and those
      who entered treatment to those who did not enter. RESULTS: Among 2659 NEP
      participants, 86% were African-American, 28% were female, 9% were employed, and
      the median age was 38 years. Requesting a drug user treatment referral was
      associated with female gender [Adjusted Odds Ratio (AOR) = 2.02], age > 38 years
      (AOR = 1.96), use of speedballs during the past 6 months (AOR = 3.38), and age >
      20 years at time of first injection (AOR = 1.59). Among 139 individuals who
      requested treatment, males were twice as likely as females to enter treatment (OR
      = 2.45). In an open-ended survey, health insurance (p = .02) and not living with
      children (p = .01) were associated with drug user treatment entry. CONCLUSIONS:
      Even though female NEP participants were more likely to request methadone
      treatment, they were less likely than males to enter treatment. Although NEPs can
      be a bridge to drug user treatment, these data suggest that barriers to utilizing
      treatment referrals are important issues to resolve, especially for women who use
      community needle exchange programs.

PMID- 12511057
TI  - Alcoholic liver disease (ALD): a new domain for prevention efforts.
AB  - Alcoholic liver disease (ALD) is a leading cause of death; yet relatively little
      has been written about it in the health behavior research literature. This paper
      will describe ALD, what factors predict ALD including findings from analyses of
      the 1998 state of California and Los Angeles County hospital discharge data, and
      possible means of preventing this disease. It is hoped that new interest among
      health behavior researchers and practitioners will be stimulated.

PMID- 12511058
TI  - Drug users and HIV-combination therapy (HAART): factors which impede or
      facilitate adherence.
AB  - The current highly active antiretroviral therapy (HAART), i.e., triple
      combination treatment including a protease inhibitor, allows for long-term
      suppression of HIV-replication. The intake guidelines, however, are very strict
      and, like many other HIV positive patients, drug users have problems in achieving
      good therapy compliance. As a result, the effectiveness of the medication therapy
      is seriously jeopardized. This qualitative study, involving in-depth interviews
      with 27 "hard drug" users in Amsterdam, seeks to provide better insights into the
      extent of adherence to HAART. In addition, factors that impede or facilitate
      adherence have been listed in order to develop and improve strategies. The study
      shows that almost half of the "hard drug" users interviewed do not adhere to the
      therapy. A large number of determinants for adherence were identified at the
      level of medication, the individual, and the environment. Many of these
      determinants can be influenced, which means that they can provide clues for the
      effective implementation of measures that may enhance effectiveness of treatment.

PMID- 12511059
TI  - Treating cocaine-using methadone patients: predictors of outcomes in a
      psychosocial clinical trial.
AB  - Cocaine-using methadone patients in two clinics were assigned to 8 months of
      enhanced methadone treatment-primarily cognitive-behavioral therapy (CBT) for
      cocaine use-while similar patients in two "sibling" clinics were assigned to
      standard methadone treatment during 1995-1998. Cocaine use declined significantly
      from baseline to 4- and 12-month follow-ups. Patients receiving CBT rated the
      quality of their counseling relationship higher and obtained more supportive
      services than those receiving standard treatment. However, study treatment
      condition itself was not associated with outcome. Baseline measures associated
      with poorer outcomes across both treatment conditions were: currently enrolled in
      methadone treatment (in contrast to being newly enrolled), higher cocaine use
      frequency, greater cocaine use associated problem recognition, and an ambivalent
      attitude toward methadone. The results are consistent with some previous clinical
      trials showing that psychosocial treatments of different intensities result in
      similar declines in cocaine use. The findings indicate that methadone maintenance
      treatment can help dually-addicted patients reduce their cocaine use.

PMID- 12511061
TI  - Bioinformatics and economics.

PMID- 12511060
TI  - Alcohol consumption in a southern European region (Galicia, Spain).
AB  - Galicia is a distinct region and an autonomous community of Spain with its own
      cultural identity. Two-thirds of the 2.7 million inhabitants live in the rural,
      reservoir of the traditional culture. Alcohol use is deeply rooted in Galician
      culture, and its abuse constitutes an important public health problem.
      OBJECTIVES: To analyze changes in alcohol consumption in the Galician adult
      population during the two last decades and its sociodemographic correlates,
      focusing on rural versus urban differences. METHODS: The principal source of
      epidemiological information is the Galicia Study of Mental Health of Adult
      Population, the first household survey representative of the Galician population,
      in which a sample of 2510 people from the population aged 16 years and older were
      asked about alcohol consumption in 1985. Data from subsequent surveys are also
      summarized and interpreted in terms of the sociocultural evolution of Galician
      society. RESULTS: The per capita annual rate of alcohol consumption in Galicia
      was 11,167cc pure alcohol, 40% higher than the national average. Personal and
      social characteristics associated with high alcohol consumption included: males
      in their thirties and young females, farmers, and low socioeconomic status. The
      traditional rural model of drinking in which alcohol is perceived as a daily
      nourishment still predominates. However, an urban consumer model is quickly
      growing, especially among young women.

PMID- 12511062
TI  - BioMOBY: an open source biological web services proposal.
AB  - BioMOBY is an Open Source research project which aims to generate an architecture
      for the discovery and distribution of biological data through web services; data
      and services are decentralised, but the availability of these resources, and the
      instructions for interacting with them, are registered in a central location
      called MOBY Central. BioMOBY adds to the web services paradigm, as exemplified by
      Universal Data Discovery and Integration (UDDI), by having an object-driven
      registry query system with object and service ontologies. This allows users to
      traverse expansive and disparate data sets where each possible next step is
      presented based on the data object currently in-hand. Moreover, a path from the
      current data object to a desired final data object could be automatically
      discovered using the registry. Native BioMOBY objects are lightweight XML, and
      make up both the query and the response of a simple object access protocol (SOAP)
      transaction.

PMID- 12511063
TI  - Phase4: automatic evaluation of database search methods.
AB  - It has become standard to evaluate newly devised database search methods in terms
      of sensitivity and selectivity and to compare them with existing methods. This
      involves the construction of a suitable evaluation scenario, the execution of the
      methods, the assessment of their performances, and the presentation of the
      results. Each of these four phases and their smooth connection usually imposes
      formidable work. To relieve the evaluator of this burden, a system has been
      designed with which evaluations can be effected rapidly. It is implemented in the
      programming language Python whose object-oriented features are used to offer a
      great flexibility in changing the evaluation design. A graphical user interface
      is provided which offers the usual amenities such as radio- and checkbuttons or
      file browsing facilities.

PMID- 12511064
TI  - Bioinformatics training in the USA.
AB  - This paper provides an overview of the history and funding of bioinformatics
      training in the USA, and summarises some of the challenges and key features
      associated with bioinformatics training programmes at PhD level. The paper
      includes compilations of current PhD bioinformatics training programmes and
      sources of funding.

PMID- 12511065
TI  - Predicting protein subcellular localisation from amino acid sequence information.
AB  - Predicting the subcellular localisation of proteins is an important part of the
      elucidation of their functions and interactions. Here, the amino acid sequence
      motifs that direct proteins to their proper subcellular compartment are surveyed,
      different methods for localisation prediction are discussed, and some benchmarks
      for the more commonly used predictors are presented.

PMID- 12511066
TI  - Global computing for bioinformatics.
AB  - Global computing, the collaboration of idle PCs via the Internet in a SETI@home
      style, emerges as a new way of massive parallel multiprocessing with potentially
      enormous CPU power. Its relations to the broader, fast-moving field of Grid
      computing are discussed without attempting a review of the latter. This review
      (i) includes a short table of milestones in global computing history, (ii) lists
      opportunities global computing offers for bioinformatics, (iii) describes the
      structure of problems well suited for such an approach, (iv) analyses the anatomy
      of successful projects and (v) points to existing software frameworks. Finally,
      an evaluation of the various costs shows that global computing indeed has merit,
      if the problem to be solved is already coded appropriately and a suitable global
      computing framework can be found. Then, either significant amounts of computing
      power can be recruited from the general public, or--if employed in an enterprise
      wide Intranet for security reasons--idle desktop PCs can substitute for an
      expensive dedicated cluster.

PMID- 12511067
TI  - Technologies for integrating biological data.
AB  - The process of building a new database relevant to some field of study in
      biomedicine involves transforming, integrating and cleansing multiple data
      sources, as well as adding new material and annotations. This paper reviews some
      of the requirements of a general solution to this data integration problem.
      Several representative technologies and approaches to data integration in
      biomedicine are surveyed. Then some interesting features that separate the more
      general data integration technologies from the more specialised ones are
      highlighted.

PMID- 12511068
TI  - Pise: software for building bioinformatics webs.
AB  - Pise is interface construction software for bioinformatics applications that run
      by command-line operations. It creates common, easy-to-use interfaces to these
      applications for the Web, or other uses. It is adaptable to new bioinformatics
      tools, and offers program chaining, Unix system batch and other controls, making
      it an attractive method for building and using your own bioinformatics web
      services.

PMID- 12511069
TI  - Protein 3D structural data--where it is, and why we need it.

PMID- 12511072
TI  - Co-expression of murine opsins facilitates identifying the site of cone
      adaptation.
AB  - Murine cones contain two opsins in the same cone, one ultraviolet (UV) and the
      other middle-wavelength sensitive (M). A long-wavelength flash only affecting M
      opsin suppresses the cone electroretinogram (ERG) produced by light absorption of
      UV-cone opsin raising the hypothesis that activation of M-cone opsin suppresses
      UV-cone opsin responses in the same cone. Here we show that pharmacologic
      blockade of synaptic transmission in the superfused murine retina, which
      eliminates interaction from second-order neurons, fails to prevent suppression of
      the UV-opsin driven pathway by long-wavelength stimuli. This proves that the
      antagonism must be occurring in the same cone, co-expressing both opsins. Our
      results show that UV-opsin suppression successively ceases in presence of the M
      opsin activating background light, which implies that cone light adaptation is
      controlled at the opsin stage, before activation of transducin. It also reveals
      the time course of a transient desensitization of cones due to post-opsin factors
      in the transduction cascade.

PMID- 12511073
TI  - Photoreceptor inner segments in monkey and human retina: mitochondrial density,
      optics, and regional variation.
AB  - The present work quantifies aspects of photoreceptor structure related to
      mitochondria, inner segment dimensions, and optical properties, as a basis for
      furthering our understanding of rod and cone function. Electron-microscopic
      analyses were performed on the retina of one stumptail macaque (Macaca arctoides)
      to obtain stereological measurements of ellipsoid mitochondrial density, and
      sizes and shapes of outer and inner segments. In addition, the distribution of
      mitochondria and the optical properties of human foveal cones were examined with
      electron microscopy and Nomarski differential interference contrast (NDIC)
      imaging. Mitochondria comprised 74-85% of cone ellipsoids and 54-66% of rod
      ellipsoids in macaque. Ellipsoid volume increased with eccentricity by 2.4-fold
      for rods and more than 6-fold for cones over eccentricities to 12.75 mm, while
      the volume of the outer segment supported by the ellipsoid was essentially
      constant for both rods and cones. Per unit volume of outer segment, cones
      contained ten times as much mitochondria as rods. In human fovea, as in the rest
      of the retina, most cone mitochondria were located in the distal inner segment.
      In the foveal center, however, there are also mitochondria in the myoid, as well
      as in the outer fiber, proximal to the external limiting membrane (ELM). Analyses
      of the optical aperture of human foveal cones, the point at which their
      refractive index clearly differs from the extrareceptoral space, showed that it
      correlated well with the location of mitochondria, except in the foveal center,
      where the aperture appeared proximal to the ELM. While mitochondria have an
      important metabolic function, we suggest that the striking differences between
      rods and cones in mitochondrial content are unlikely to be determined by
      metabolic demand alone. The numerous cone mitochondria may enhance the waveguide
      properties of cones, particularly in the periphery.

PMID- 12511074
TI  - Responses in extrastriate cortex to optic flow during simulated turns.
AB  - An observer locomoting along a straight path sees a pattern of optic flow in
      which images move approximately radially outward from his heading point. If the
      observer turns, the optic flow field changes markedly because each object's image
      now has a component of horizontal motion added to its "optic flow" motion. We
      tested the responses of 326 cells in the cat's extrastriate area LS (lateral
      suprasylvian visual area) to movies simulating the optic flow seen during
      locomotion in a straight line, and during various simulated turns to the left and
      right. About 60% of 326 cells tested responded to optic flow simulating turns. Of
      most interest was a subset of cells, 15% of the total, that had "turn-selective"
      responses. They responded significantly better to turns in a particular direction
      (usually to the contralateral side) than to turns in the opposite direction or to
      optic flow simulating straight-ahead locomotion. For each cell, we generated a
      display of fronto-parallel motion with a direction and speed that matched the
      image motion in the preferred turn movie, as seen at the receptive-field center.
      Most turn-selective cells responded significantly better to their preferred turn
      movie than to this fronto-parallel stimulus. We examined the role of cells'
      selectivity for stimulus direction, speed, and acceleration in determining cell
      preference for particular turns. Direction preference played some role for most
      cells, but about a third of the cells preferred turn movies that did not reflect
      their direction selectivity. Other factors, including the presence of opposing
      motion, only rarely appeared to determine cell preferences for particular turn
      movies.

PMID- 12511075
TI  - Contrast adaptation: paradoxical effects when the temporal frequencies of
      adaptation and test differ.
AB  - Previous studies of human contrast adaptation employing visually evoked
      potentials (VEP) have revealed contradictory results, namely, either a reduction
      or an enhancement in VEP amplitude. In a cross-adaptation experiment, we explored
      the possibility that differences in the temporal frequency of adapting and test
      patterns played a role. Phase-reversing checkerboard stimuli [1-deg check size,
      temporal frequency 8.5 or 17 reversals per second (rps)] served as adaptation and
      test pattern with contrasts of 0 or 97%. In 13 subjects, we recorded both retinal
      (PERG) and cortical (VEP) steady-state responses simultaneously. In a balanced
      block design, all four combinations of the temporal adaptation and test
      frequencies were employed. Contrast adaptation reduced the PERG amplitude by
      about 20% in every temporal condition (P < 0.001). The VEP amplitude was strongly
      affected by adaptation, but the effect differed in magnitude and sign depending
      on condition: With identical adaptation and test frequency, amplitude was reduced
      by 15% (P = 0.07) at 8.5 rps and by 38% at 17 rps (P < 0.05). Adapting at 8.5 rps
      and testing at 17 rps had a tiny (14%) insignificant effect, whereas adapting at
      17 rps and testing at 8.5 rps revealed an amplitude enhancement of 27% (P <
      0.05). These strong temporal cross-adaptation effects (in the VEP, but not in the
      PERG) suggest that the adaptable cortical mechanisms (gain control) can be
      narrowly tuned in their temporal properties. A sizable adaptation effect can even
      change its sign when varying the temporal frequency by a factor of two. This
      finding resolves contradictions between previous VEP adaptation studies and
      reconciles them with psychophysical findings.

PMID- 12511076
TI  - Rabbit retinal ganglion cell responses mediated by alpha-bungarotoxin-sensitive
      nicotinic acetylcholine receptors.
AB  - The responses of many ganglion cells in the rabbit retina are mediated, at least
      in part, by acetylcholine (ACh) acting on neuronal nicotinic acetylcholine
      receptors (nAChRs). nAChRs are comprised of alpha and beta subunits; three beta
      subunits and nine alpha subunits of nAChRs have been identified and these
      subunits can combine to form a large number of functionally distinct nAChR
      subtypes. We examined the effects of cholinergic agents on the light-evoked
      responses of ganglion cells to determine which nAChR subtypes mediate the effects
      of ACh. Extracellular recordings of retinal ganglion cells were made in intact
      everted eyecup preparations and nicotinic agonists and antagonists were added to
      the superfusate. While several ganglion cell classes exhibited methyllycaconitine
      (MLA) sensitivity, the directionally selective (DS) ganglion cells were most
      sensitive; exposure to 30 nanomolar MLA, a concentration reportedly too low to
      affect alphaBgt-insensitive nAChRs, suppressed the stimulus-evoked responses of
      DS cells without eliminating directional selectivity. Epibatidine, which at low
      concentrations is an agonist selective for alphaBgt-insensitive nAChRs,
      stimulated firing of various cell types including DS ganglion cells at low
      nanomolar concentrations. The effects of the various agents tested persisted
      under cobalt-induced synaptic blockade. The low nanomolar MLA and epibatidine
      sensitivity of DS cells suggests that DS ganglion cells express both alphaBgt
      sensitive and alphaBgt-insensitive nAChRs. Other ganglion cell types appear to
      express only alphaBgt-sensitive nAChRs but not alphaBgt-insensitive nAChRs.

PMID- 12511077
TI  - The spatial extent over which neurons in macaque striate cortex pool visual
      signals.
AB  - We recorded activity of single units in macaque monkey primary visual cortex (V1)
      to define the retinotopic extent of the visual inputs that drive or modulate V1
      neuron responses in parafoveal and peripheral (calcarine) cortex. We used high
      contrast drifting grating stimuli to define the extent of the area over which
      responses summate and the extent of the receptive-field surround. We found
      responses of most V1 cells to summate over 1 deg, with a suppressive surround
      typically twice that in diameter, though for some cells (even in parafoveal V1)
      surrounds exceeded 13 deg in diameter. Surprisingly, we found no significant
      laminar differences in these dimensions or in the strength of surround
      suppression. We found that surround suppression in most cells arises from both
      the ends and sides of the receptive field. Our measures indicate that the
      strongest modulatory input arises from regions immediately adjacent to the
      excitatory summation area. These physiological measures suggest that the high
      contrast summation field of V1 neurons can be accounted for by the sum of lateral
      geniculate nucleus (LGN) inputs offered to the local cortical column, with
      monosynaptic lateral connections within area V1 adding the larger dimensions of
      the low-contrast summation field and the near surround. Neither of these inputs
      suffice to explain the largest surrounds, which most likely derive from feedback
      from extrastriate visual areas.

PMID- 12511078
TI  - Expression and distribution of ionotropic glutamate receptor subunits on parasol
      ganglion cells in the primate retina.
AB  - The response properties of postreceptoral sensory neurones are determined by the
      properties of their input neurones, by intrinsic membrane properties, and by the
      properties of neurotransmitter receptors on the soma and dendritic tree. We
      previously showed that inhibitory neurotransmitter (GABA(A) and glycine)
      receptors on a well-characterised sensory neurone, the parasol ganglion cell in
      the primate retina, are segregated towards the distal part of the dendritic tree.
      Here we studied the distribution of excitatory ionotropic glutamate receptor
      subunits on the dendrites of parasol cells in the retina of a New World monkey,
      the marmoset, Callithrix jacchus. Individual ganglion cells were intracellularly
      injected in an in vitro retinal wholemount preparation. Ionotropic glutamate
      receptor subunits. including AMPA (GluR1-4), kainate (GluR6/7), NMDA (NR1C2')
      subunits, and the orphan receptors delta1 and delta2 were visualized with
      immunocytochemical methods. Immunoreactive puncta that colocalized with the
      dendrites of ganglion cells were analyzed using standard and/or confocal light
      microscopy. Colocalized puncta were present on parasol dendrites for all subunits
      studied, but their density was much lower (approximately 1/5) than previously
      reported for inhibitory (GABA and glycine) receptors. Segregation of the
      glutamate receptor clusters (GluR1, GluR6/7 subunits) to the peripheral dendrites
      was less marked than that shown for GABA and glycine receptor clusters. No sign
      of segregation of colocalized puncta to the peripheral part of the dendritic
      field was seen with antibodies to the GluR2, GluR2/3, GluR4, delta1/2, or NR1C2'
      subunits. The results suggest that although there is diverse expression of
      glutamate receptor subtypes, the glutamatergic synapses form only a small
      proportion of the total synaptic input to primate ganglion cells. They further
      suggest that the processes which control distribution of excitatory and
      inhibitory synapses on the dendritic field of ganglion cells are, at least to
      some extent, independent.

PMID- 12511079
TI  - Visual pigments and dichroism of anchovy cones: a model system for polarization
      detection.
AB  - The retinas of anchovies have two unique photoreceptor types: "bifid" and "long"
      cones (Fineran & Nicol, 1976). The outer segments of these cells contain multiple
      layers of membranes (lamellae) oriented longitudinally (axially). This
      orientation is distinct from that in all other vertebrate rods and cones, where
      the lamellae are stacked transversely with their planes perpendicular to the
      incident light path. Although the common arrangement provides optimal absorption
      for normally incident light rays, it is also insensitive to the rays' direction
      of vibration (i.e. their polarization). In contrast, the two mutually
      perpendicular sets of axially oriented lamellae segregated into bifid and long
      cones could function as the principal analyzers for linearly polarized light, as
      previously hypothesized (Fineran & Nicol, 1976, 1978). Here, we report on a
      microspectrophotometric study that shows (1) the presence of two spectrally
      distinct visual pigments in the three photoreceptor types of the bay anchovy
      retina; these are typical vertebrate pigments in that they bleach, when exposed
      to light, and have absorption spectra like all other vitamin A1-based visual
      pigments; (2) that the rods and cones exhibit dichroic absorption of light in
      accordance with their lamellar orientation, and (3) that the two cone types of
      the retina contain a spectrally indistinguishable pigment with peak absorbance
      (lambda(max)) around 540 nm, while the rods contain a rhodopsin-like pigment with
      lambda(max) near 500 nm. Compared to other vertebrates, anchovies are remarkable
      for using a monochromatic cone system with unusual specializations supportive of
      a polarization detection system.

PMID- 12511080
TI  - Fixational ocular motor control is plastic despite visual deprivation.
AB  - The aim of this study was to assess the plasticity of human voluntary fixational
      eye movement control in relation to visual experience/chronic visual deprivation.
      Twelve blind adults participated (self-reported vision < or = light perception in
      each eye; age range = 23-56 years; visual experience range = 0-28 years;
      blindness duration range = 6-55 years). Infrared-based recordings of horizontal
      eye movements were made before, during, and immediately after three 30-s periods
      of auditory ocular motor feedback, while participants were instructed to look
      straight ahead and keep their eyes as steady as possible. Percent change in
      horizontal displacement of the eye during and after feedback was compared with
      the no-feedback baseline. Eleven of the 12 individuals demonstrated feedback
      mediated increase in eye stability, which improved as a function of visual
      experience. Improved eye stability was inversely related to duration of
      blindness. Clearly, blind adults can use nonvisual external feedback to stabilize
      gaze. Thus, the fixational subsystem can exhibit improved voluntary control
      despite chronic visual deprivation. Possible cortical and subcortical mechanisms
      are discussed.

PMID- 12511081
TI  - Large-scale morophological survey of rat retinal ganglion cells.
AB  - Ganglion cells in an isolated wholemount preparation of the rat retina were
      labeled using the "DiOlistic" labeling method (Gan et al., 2000) and were
      classified according to their morphological properties. Tungsten particles coated
      with a lipophilic dye (DiI) were propelled into the wholemount 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 types based on their
      soma size, dendritic-field size, branching pattern, and level of stratification.
      Broadly monostratified cells were classified into three types: 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 soma,
      medium-to-large dendritic field). Bistratified cells were classified as RG(D).
      Several subtypes were identified within each ganglion cell group. A number of new
      subtypes were discovered and added into the existing catalog, among them were two
      types of bistratified cells. This study therefore represents the most complete
      morphological classification of rat retinal ganglion cells available to date.

PMID- 12511082
TI  - Effects of the destruction of starburst-cholinergic amacrine cells by the toxin
      AF64A on rabbit retinal directional selectivity.
AB  - The effects of intraocular injections of ethylcholine mustard aziridinium ion
      (AF64A), an irreversible inhibitor of choline uptake, on the rabbit retina were
      assessed electrophysiologically, pharmacologically, anatomically, and
      behaviorally. Survival times from 1 day to 30 days were investigated. After 24 h,
      the shortest time tested, the directional selectivity of On-Off responding
      ganglion cells having the characteristic morphology of On-Off directionally
      selective directionally selective (DS) ganglion cells, as revealed by
      intracellular dye injection, was significantly reduced, both by an apparent
      decrease of preferred direction responses and an increase in responses to null
      direction movement. No toxin-mediated changes in the dendritic trees of these
      cells were noted. Cells in AF64A-affected retinas having the DS morphology did
      not respond significantly to GABAergic or cholinergic agents such as picrotoxin
      and eserine, but did respond to nicotine. Recordings from a small random sample
      of other ganglion cell classes in the same retinas yielded no obvious changes in
      response properties. The direct effects on starburst (cholinergic) amacrine
      cells, which were identified by intraocular injection of the fluorescent dye DAPI
      with the AF64A, were investigated by intracellular injections of Lucifer yellow,
      and by immunohistochemical staining with antibodies to choline acetyltransferase
      (ChAT). Although starburst amacrine cell somas survived the AF64A treatment for
      at least several days, the dendrites could not be visualized by fluorescent dye
      injection in affected retinas due to dye leakage of the injected fluorescent dye
      from either the soma or proximal dendritic region. ChAT staining revealed a
      sequence in which ChAT-positive cells were undetectable first in the inner
      nuclear layer, and then in the ganglion cell layer. Cholinergic amacrine cells in
      the central retina were also affected before those in the periphery. The
      electrophysiological changes observed typically preceded the loss of ChAT
      activity. Behavioral tests for optokinetic nystagmus responses also revealed a
      lack of such responses in the affected eyes.

PMID- 12511083
TI  - Organization of reciprocal connections between the perigeniculate nucleus and
      dorsal lateral geniculate nucleus in the cat: a transneuronal transport study.
AB  - Cells of the cat's perigeniculate nucleus (PGN), part of the visual sector of the
      thalamic reticular nucleus (TRN), provide GABAergic inhibition to the A and A1
      layers of the dorsal lateral geniculate nucleus (LGNd) and, therefore, may
      control information flow from the retina to the cortex. Previous
      electrophysiological experiments suggested that the PGN may be subdivided on the
      basis of ocular dominance thus reflecting the afferent and efferent projections
      with lamina A and A1 of the LGNd. The present study utilized the ability of wheat
      germ agglutinin-horseradish peroxidase (WGA-HRP) to be transported
      transneuronally following intraocular injections in four cats to examine whether
      there is any anatomical evidence for eye specific layers within the PGN. Sections
      were processed with tetramethylbenzidine. Light WGA-HRP transneuronal labeling of
      LGNd collaterals and somata were seen in the PGN and very light labeling (but not
      somata) was seen in the TRN. Neither the cells of the PGN projecting to the LGNd
      nor the LGNd relay collaterals within the PGN were clearly organized into
      nonoverlapping laminae related to the eye specific layers of the LGNd. However,
      parts of the PGN immediately adjacent to the LGNd appear devoid of connections
      with lamina A1 thus creating a thin monocular segment for the contralateral eye.

PMID- 12511084
TI  - APB differentially affects the cone contributions to the zebrafish ERG.
AB  - APB (DL-2-amino-4-phosphonobutyric acid) has been found to affect the retinal
      processing of many vertebrate species as evidenced by the suppression of the b
      wave component of the electroretinogram (ERG). The present study examined the
      effects of APB on the cone contributions to the ERG response of adult zebrafish
      (Danio rerio). ERG responses were obtained from light-adapted adult zebrafish
      following intravitreal injection of either saline alone or saline with various
      concentrations of APB ranging from 10 microm to 500 microM. Visual stimuli were
      200-ms flashes of various wavelengths and irradiances. Spectral sensitivity
      functions were calculated from the irradiance versus response amplitude functions
      of the a-, b-, and d-wave components of the ERG response. Saline had no effects
      on the ERG response. However, APB had differential effects on the sensitivity of
      the b- and d-wave components. The effects of APB on the b-wave component were
      most apparent in the ultraviolet and short-wavelength portions (320-440 nm) of
      the spectral sensitivity function, although the b-wave was not completely
      eliminated at these wavelengths. APB-treated subjects were found to possess the
      same cone mechanisms (L-M and M-S) in the middle- and long-wavelength areas of
      the spectrum as saline injected subjects, although absolute sensitivity was lower
      for the APB-injected subjects. Spectral sensitivity based on the d-wave response
      was affected by APB but only in the short-wavelength region. All results appear
      to be independent of the APB dose. These results support the notion that
      glutamate receptors play a specific role in zebrafish visual processing. In
      addition, the effects of APB support recent anatomical evidence that the
      zebrafish retina may possess different types of glutamate receptors.

PMID- 12511085
TI  - Cholecystokinin-like immunoreactive amacrine cells in the rat retina.
AB  - High levels of endogenous cholecystokinin (CCK) are present in the rat retina
      (Eskay & Beinfeld, 1982), but the cellular localization and physiological actions
      of CCK in the rat retina are uncertain. The goals of this study were to
      characterize the cells containing CCK, identify cell types that interact with CCK
      cells, and investigate the effects of CCK on rod bipolar cells. Rat retinas were
      labeled with antibody to gastrin-CCK (gCCK) using standard immunofluorescence
      techniques. Patch-clamp methods were used to record from dissociated rod bipolar
      cells from rats and mice. Gastrin-CCK immunoreactive (-IR) axons were evenly
      distributed throughout the retina in stratum 5 of the inner plexiform layer of
      the rat retina. However, the gCCK-IR somata were only detected in the ganglion
      cell layer in the peripheral retina. The gCCK-IR cells contained glutamate
      decarboxylase, and some of them also contained immunoreactive substance P.
      Labeled axons contacted PKC-IR rod bipolar cells, and recoverin-IR ON-cone
      bipolar cells. CCK-octapeptide inhibits GABA(C) but not GABA(A) mediated currents
      in dissociated rod bipolar cells.

PMID- 12511086
TI  - An albino-like decussation error in the optic chiasm revealed by anomalous ocular
      dominance columns.
AB  - We report a unique anomaly in the ocular dominance column pattern of a single,
      normally pigmented macaque monkey. The column pattern contained large monocular
      areas inserted between the normal columns and the dorsal V1 border. These
      monocular regions received transneuronal input from the contralateral eye,
      indicating that a small population of temporal ganglion cells erroneously
      decussated at the optic chiasm. Projection of the column pattern back onto the
      visual field showed that the monocular wedges represented a approximately 5-deg
      sector of ipsilateral field. This corresponded to the extent of naso-temporal
      overlap of ganglion cells in the normal retina, suggesting an error in axon
      guidance affecting cells close to the vertical midline of the retina. The
      consequences of the crossing error in this animal were threefold: it produced an
      anomalous monocular zone near the V1 border, the vertical meridian was not
      represented at the V1 border, and points near the vertical meridian were
      represented twice in the brain, once in each hemisphere.

PMID- 12511087
TI  - Transgenic expression of a GFP-rhodopsin COOH-terminal fusion protein in
      zebrafish rod photoreceptors.
AB  - To facilitate the identification and characterization of mutations affecting the
      retina and photoreceptors in the zebrafish, a transgene expressing green
      fluorescent protein (GFP) fused to the C-terminal 44 amino acids of Xenopus
      rhodopsin (Tam et al., 2000) under the control of the 1.3-kb proximal Xenopus
      opsin promoter was inserted into the zebrafish genome. GFP expression was easily
      observed in a ventral patch of retinal cells at 4 days postfertilization (dpf).
      Between 45-50% of the progeny from the F1, F2, and F3 generations expressed the
      transgene, consistent with a single integration event following microinjection.
      Immunohistochemical analysis demonstrated that GFP is expressed exclusively in
      rod photoreceptors and not in the UV, blue, or red/green double cones.
      Furthermore, GFP is localized to the rod outer segments with little to no
      fluorescence in the rod inner segments, rod cell bodies, or rod synapse regions,
      indicating proper targeting and transport of the GFP fusion protein. Application
      of exogenous retinoic acid (RA) increased the number of GFP-expressing cells
      throughout the retina, and possibly the level of expressed rhodopsin. When bred
      to a zebrafish rod degeneration mutant, fewer GFP-expressing rods were seen in
      living mutants as compared to wild-type siblings. This transgenic line will
      facilitate the search for recessive and dominant mutations affecting rod
      photoreceptor development and survival as well as proper rhodopsin expression,
      targeting, and transport.

PMID- 12511088
TI  - Supramolecular interaction between water-soluble calix[4]arene and ATP--the
      catalysis of calix[4]arene for hydrolysis of ATP.
AB  - The catalysis effect of water-soluble calix[4]arene C[4] (calix[4]arene
      5,11,17,23-tetrasulfonate) on hydrolysis of ATP in aqueous solution was studied
      by HPLC. Using laser photolysis and pulse radiolysis, the supramolecular
      interaction between water-soluble calix[4]arene and ATP was investigated.

PMID- 12511089
TI  - Vibrational analysis of substituted phenols: part I. Vibrational spectra, normal
      coordinate analysis and transferability of force constants of some formyl-,
      methoxy-, formylmethoxy-, methyl- and halogeno-phenols.
AB  - The Raman (including FT-Raman) and Fourier transform infrared (FTIR) spectra of
      1,3-dihydroxybenzene, 1,4-dihydroxybenzene, 2-hydroxybenzaldehyde, 2-hydroxy-3
      methoxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 1,2-dihydroxy-3
      methoxybenzene, 2,5-dihydroxytoluene, 2,6-dihydroxytoluene, pentachlorophenol and
      pentabromophenol were measured. Raman polarisation measurements were made
      wherever possible. A normal coordinate treatment was carried out for both the in
      plane and out-of-plane vibrations of these molecules using a 123-parameter
      modified valence force field. An overlay least-squares technique was employed to
      refine the force constants using 347 frequencies of 10 molecules. The reliability
      of these force constants was tested by making a zero-order calculation for 10
      related molecules. Unambiguous vibrational assignments of all the fundamentals
      were made using the potential energy distributions and eigenvectors.

PMID- 12511090
TI  - Optical properties of Er3+ ions doped in oxyfluoroborate glass.
AB  - In this paper the Stark components of 4S(3/2), 2H(11/2) and 4I(15/2) levels of
      Er3+ ion doped in oxyfluoroborate glass have been resolved using laser excitation
      and fluorescence measurements. The lifetime of 4S(3/2) level as a function of
      Er3+ concentration in the glass host has also been measured. Concentration
      quenching due to interaction among rare earth ions and the mechanism responsible
      for the same has been elucidated. The Judd-Ofelt analysis of the absorption
      spectrum has also been carried out.

PMID- 12511091
TI  - Resonance double light scattering method for the determination of proteins with
      morin-CTMAB.
AB  - A new determination method of proteins with the limit of determination at
      nanogram levels is proposed by using a common spectrofluorimeter to detect
      intensity of resonance double line scattering (RDLS). Proteins including bovine
      serum albumin (BSA), human serum albumin (HSA) can combine with morin and
      cetyltrimethylammonium briomide (CTMAB) in the pH range 7.0-8.0 and produce
      enhanced RDLS signal at lambda(ex)/lambda(em) 305.0/610.0 nm. Optimization
      conditions for the morin-protein-CTMAB interaction were tested. In the studied
      system, BSA/CTMAB/morin = 1:2:3. The association constant of morin with BSA is
      5.2 x 10(4). Under the optimum conditions, the linear range is 7.5 x 10(-8)-1.0 x
      10(-5) g/ml for BSA, 2.5 x 10(-8)-5.0 x 10(-6) g/ml for HSA. The detection limits
      (S/N = 3) are 66.0 ng/ml for BSA and 23.0 ng/ml for HSA, respectively. Four
      synthetic samples were analyzed satisfactorily.

PMID- 12511092
TI  - Infrared spectra of new Re(III) complexes with thiourea derivatives.
AB  - Complexes of the type [Re(III)L6]X3, with L = thiourea, N-methylthiourea, N
      ethylthiourea or N,N'-dimethytlthiourea and X = Cl- or PF6-, were prepared as
      suitable precursors for the synthesis of new rhenium complexes potentially useful
      in nuclear medicine. The infrared (IR) spectra of these complexes were recorded
      and analyzed and a general vibrational pattern for Re(III) complexes with
      thiourea derivatives could be established. Approximate assignments for N
      allylthiourea and N-ethylthiourea are also proposed for the first time. The
      synthesis of the new complex [Re(III)(N-allylthiourea)6](PF6)3 is also reported,
      and information about its structural characteristics was obtained comparing its
      IR spectrum with those of the other complexes of the investigated series.

PMID- 12511093
TI  - Photoacoustic spectra and modes of vibration of TNT and RDX at CO2 laser
      wavelengths.
AB  - IR spectra in the 'Finger Print' spectral range has great importance in
      qualitative and quantitative analysis of explosives like trinitrotoluene (TNT)
      and cyclotrimethyltrinitramine (RDX). Highly resolved IR bands of these compounds
      have been recorded in the 9.6 and 10.6 microm regions of CO2 laser. TNT and RDX
      are large molecules each having 21 atoms and it is very difficult to assign the
      modes of vibrations by comparison with those in other molecules making the
      vibrational assignments of observed bands a difficult task. The ab initio quantum
      chemical calculation is used for determining the molecular geometries and modes
      of vibration of these molecules with a view to assign their normal modes in the
      high resolution vibrational photoacoustic spectra. These assignments are very
      reliable in view of the good agreement between the observed and calculated
      frequencies of deuterated TNT.

PMID- 12511094
TI  - Synthesis, structure, electronic and vibrational spectra of 9-(Diethylamino)
      benzo(a)phenoxazin-7-ium-5-N-methacrylamide.
AB  - The electronic and vibrational spectra of 9-(Diethylamino)-benzo(a)phenoxazin-7
      ium-5-N-methacrylamide (Nile Blue-5-N-methacrylamide) are measured, and the
      results are compared with the theoretical values obtained by quantum chemical
      calculations. The geometry, electronic transitions, charge distribution, and the
      IR normal modes of this new dye and of its precursor Nile Blue have been computed
      by using Density Functional Theory (DFT) method with the functional B3LYP and the
      6-31G(d) Gaussian basis set. The molecular properties of the two dyes, predicted
      and observed, are very similar in the electronic ground state. In the excited
      state, however, the longer lifetime and larger fluorescence quantum yield of the
      Nile Blue-5-methacrylamide is ascribed to an inhibition of the twisted
      intramolecular charge transfer (TICT) process, when the NH2 is substituted by the
      methacrylamide in the 5-position of the aromatic extended ring of the dye. The
      change in charge density of the N atom in 5-position, as well as the difference
      in dipole moment and ionization potential of the two dyes molecules, explain the
      attenuation of TICT process. The vibration spectra of both dyes are simulated
      properly by using the DFT method.

PMID- 12511095
TI  - Study on the spectroelectrochemical properties of S-benzyl-N-(ferrocenyl-1-methyl
      metylidene)-dithio-carbazate nickel (II) complex.
AB  - Mechanism of electron transfer of a bridge biferrocene complex, Ni(LSB)2, derived
      from the Schiff base ligand, HLSB, S-benzyl-N-(ferrocenyl-1-methyl-metylidene)
      dithio-carbazate Ni(LSB)2, during redox processes is illuminated by in-situ
      Fourier transform infrared (FTIR) spectroelectrochemistry. The results indicated
      that two consecutive one-electron steps were involved which gives the
      corresponding mono- and di-ferricenium cations, respectively. This complex
      exhibits moderately strong degree of electronic communication between the two
      ferrocene moieties, taking place through the skeleton chain of the ligand due to
      an extensive electron delocalization in the molecule. Possible pathways of
      electron transfer of Ni(LSB)2 during the redox processes are postulated.

PMID- 12511096
TI  - A study of the resonance nonlinear scattering of silver atomic clusters.
AB  - The Ag cluster in solution has been prepared by a microwave high-pressure
      procedure. There is a maximum resonance Rayleigh scattering (RRS) peak at 425 nm
      (7.06 x 10(14) Hz) and a smaller RRS peak at 850 nm (1/2 x 7.06 x 10(14) Hz) by
      synchronous scattering at lambda(ex) = lambda(em). It is a nonlinear optical
      medium. When scattering the emission wavelength (lambda(em)) as the excited
      wavelength (lambda(ex)) at 425 nm (7.06 x 10(14) Hz), a maximum RRS peak was
      observed at 425 nm (7.06 x 10(14) Hz). A 1/2 fraction scattering peak at 850 nm
      (1/2 x 7.06 x 10(14) Hz) was also investigated. When lambda(ex) is at 850 nm
      (3.53 x 10(14) Hz), a frequency-doubling scattering peak at 425 nm is observed,
      and a RRS peak is displayed at 850 nm (3.53 x 10(14) Hz). When the lambda(ex) is
      two times longer than the maximum RRS wavelength (the strongest wavelength of
      pump band lambda(pb)) of an atomic cluster, a nonlinear scattering frequency
      doubling peak (lambda(pb)) exhibits at half of the lambda(ex), which is stronger
      than the RRS peak. This phenomenon is defined as pump effect.

PMID- 12511097
TI  - Vibrational spectra and structure of benzil and its 18O- and d10-labelled
      derivatives: a quantum chemical and experimental study.
AB  - Geometry and vibrational spectroscopic data of benzil-d0 benzil-d10 and benzil
      18O calculated at various levels of theory (RHF/6-31G*, B3LYP/6-31G*, BLYP/6
      31G*) are reported. The theoretical results are discussed mainly in terms of the
      comparisons with infrared (4000-100 cm(-1)) and Raman (4000-50 cm(-1)) spectral
      data. The calculated isotopic frequency shifts, induced by the 18O- and d10
      labeling, are in a good agreement with the measured values. A complete
      vibrational assignment was made with the help of ab initio force field
      calculations. The data thus obtained were used for reassigning some vibrational
      frequencies. The results of the optimized molecular structure obtained on the
      basis of RHF and the DFT calculations are presented and compared with the
      experimental X-ray diffraction for the benzil-d0 single crystal. It turns out
      that the best structural parameters are predicted by the B3LYP/6-31G* method.

PMID- 12511098
TI  - The anomalous solvent effect in the vibrational spectrum of 2,3-diphenyl
      cycloprop-2-enone: an experimental and theoretical investigation.
AB  - 2,3-Diphenyl-cycloprop-2-enone (DPC) was investigated aiming to understand the
      origins of the anomalous solvatochromism in its vibrational spectrum. Its Raman
      and IR spectra in several solvents were obtained revealing that the v(C=C) mode
      is much more sensitive to the solvent than the v(C=O) mode. Hartree-Fock and
      density functional theory calculations were undertaken for obtaining the
      structure and the vibrational spectra of DPC and 2,3-dimethylcycloprop-2-enone
      (DMC), revealing that both in terms of structure as well as of vibrational
      spectrum, DPC and DMC are very similar. Such results indicated that DMC could be
      used as a model system to simulate the solvent effect in DPC, what was done using
      three different methods: the first takes into account the dielectric effect via
      the self-consistent reaction field (SCRF); the second is the supermolecular
      approach that considers explicity the formation of solute-solvent clusters and
      the third is a combined approach, SCRF + supermolecule. The anomalous
      solvatochromism in the vibrational spectrum of DPC can be understood on basis of
      the significant participation of the v(C=O) mode in the one assigned to the
      v(C=C) vibration, as well as by the presence of a Fermi resonance involving the
      former. In addition, the v(C=O) mode involves a significant participation of the
      (C-C) mode (C(cyclopropene)-C(phenyl)) and the two interatomic distances, C=O and
      C-C, show opposite trends with increasing solvent polarity. Summing up, the
      anomalous solvatochromic effect of DPC can be understood by the complex
      composition of its v(C=O) mode that, in addition, is affected by the presence of
      a Fermi resonance.

PMID- 12511099
TI  - Hyper-Rayleigh scattering (HRS) spectroscopy applied to nanoparticulate TiO2.
AB  - We have probed the photophysics of nanoparticulate TiO2 using hyper-Rayleigh
      scattering (HRS) spectroscopy. We find that despite its Wurtzite structure, the
      anatase particles we prepared are only weakly hyperpolarizable, which suggests
      that second harmonic generation may couple transitions which are: (a) only weakly
      allowed, i.e. indirect; or (b) associated with states, probably surface states,
      of low density. Addition of a carboxy-functional spectral sensitizing dye further
      quenches second harmonic generation. We hypothesize that the dye competes
      efficiently with hyperpolarizable surface states for capture of photoholes. We
      also found that HRS could be used to follow formation of these
      photocatalyticallly active nanoparticles by acid-catalyzed oxopolymerization of
      Ti(O1Pr)4. The polymerization is a pseudo-first order process consistent with
      occurrence of an S(N)1 reaction at Ti(IV) in the rate determining step.

PMID- 12511100
TI  - FT-infrared band analysis and temperature programmed dessorption for the Y, L and
      ferrierite zeolites.
AB  - With the aim to qualifying and quantifying the acidity of the Y, L and ferrierite
      zeolites, an infrared band analysis of pyridine adsorption and programmed
      temperature dessorption measurements were carried out to a set of nine samples of
      the Y, L and ferrierite zeolites. The infrared spectra before and after the
      pyridine adsorption process had revealed that the ferrierite zeolite shows,
      almost in the totality, Bronsted acid sites. The Y and L zeolites present, also,
      significative concentrations of Bronsted and Lewis acid sites. These facts allow
      to conclude that zeolite ferrierite is the strongest acid zeolite among these
      three types.

PMID- 12511101
TI  - Thermal and kinetic studies on solid complexes of 2-(2-benzimidazolylazo)-4
      acetamidophenol with some transition metals.
AB  - The preparation and characterization of 2-(2-benzimidazolylazo)-4-acetamidophenol
      (BIAAP) complexes are reported. Different physico-chemical methods like IR,
      Magnetic, solid reflectance spectra and molar conductance, were used to
      investigate the structure of BIAAP complexes. In particular, the thermal
      decomposition of Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes of
      BIAAP is studied in nitrogen atmosphere. All the complexes do not contain
      coordinated water molecules but contain (2-4) water molecules of crystallization.
      The water molecules were removed in a single step. The complexes of Co(II) and
      Ni(II) ions exhibited a phase transition and the decomposition or combustion of
      BIAAP occurred in the second and subsequent steps. The final decomposition
      products were identified by mass spectrometry as the corresponding metal oxides
      or carbonate. The activation thermodynamic parameters, such as, energy of
      activation, enthalpy, entropy and free energy change of the complexes were
      evaluated and the stabilities of the thermal decomposition of the complexes are
      discussed. From the kinetic point of view, it is found that the thermal stability
      of the complexes follows the order Ni(II) > Cu(II) > Zn(II) > Fe(III) > Co(II) >
      Cd(II).

PMID- 12511102
TI  - Investigations of the g factors and hyperfine structure parameters for Er3+ ion
      in zircon-type compounds.
AB  - The electron paramagnetic resonance (EPR) g factors g(parallel), g(perpendicular)
      and hyperfine structure parameters A(parallel), A(perpendicular) of the
      tetragonal Er3+ centers in zircon-type compounds YXO4 (X = As, P, V), ScVO4 and
      RSiO4 (R = Zr, Hf, Th) are calculated from the perturbation formulas of EPR
      parameters for 4f11 ion in tetragonal symmetry. In these formulas, the second
      order perturbation contributions are included in addition to the first-order
      perturbation contributions considered in the previous papers. The crystal-field
      parameters used in the calculations are obtained by analyzing the optical
      spectral data from the superposition model. Although the superposition model
      intrinsic parameters An(R0) used in this paper for Er3+ in various zircon-type
      compounds are not as scattered as those in the previous paper, the calculated
      results of both the optical spectra and EPR parameters show better agreement than
      those in the previous paper with the observed values, suggesting that the above
      calculation method and parameters are more reasonable. The contributions of the
      second-order perturbation terms to EPR parameters are also discussed.

PMID- 12511103
TI  - Raman spectra of (NH4)3ZnCl4NO3 and (ND4)3ZnCl4NO3 between 295 and 60 K.
AB  - Raman spectra from polycrystalline samples of (NH4)3ZnCl4NO3 and (ND4)3ZnCl4NO3
      have been studied in the temperature range 60-295 K. Internal modes of both
      nitrate and tetrachlorozincate ions show expected band narrowing and
      intensification at lower temperature but no significant changes in frequency. Two
      bands in the lattice region of both compounds, assigned to nitrate ion libration
      and rocking, show linear increases in frequency with lowering temperature. The
      intensity of the libration mode shows a linear decrease with lowering
      temperature, but the intensity of the rocking mode is relatively insensitive to
      temperature change. Ammonium ion bands show greater structure at low temperature,
      suggesting differentiation between the two crystallographically distinct types of
      cation. The observed spectral changes are interpreted on the basis of increasing
      ordering and effectiveness of hydrogen bonds between ammonium ions and nitrate
      ions at low temperatures. The Raman spectra give no evidence of discontinuous
      changes in frequency or intensity, which would signal temperature-dependent
      transitions of the crystal structure. Unlike the related single-anion compounds
      NH4NO3 and (NH4)2ZnCl4, the room-temperature structure of (NH4)3ZnCl4NO3 and
      (ND4)3ZnCl4NO3 appears to persist at least to 60 K, being stabilized by
      increasingly ordered hydrogen bonding.

PMID- 12511104
TI  - Proteins at air-water interfaces studied using external reflection circular
      dichroism.
AB  - In this report we describe the first attempts to record external reflection
      circular dichroism (ERCD) spectra of beta-lactoglobulin solutions. It is shown
      that the accumulated proteins at and near the air-water interface can be detected
      using ERCD and that the signals obtained contain information on the
      conformational properties and concentration of the proteins residing at the
      interface. The local protein concentration and its conformation are in full
      agreement with previous observations using external reflection infrared
      spectroscopy. The ERCD signals are dominated by linear dichroism (LD) due to non
      ideal behavior of the instrumental optics, but can be explained for using the
      theoretical description of chiral reflection. This allows the analysis of ERCD
      spectra of protein solutions. The measured ERCD signals are described accurately
      in the region between 190 and 220 nm, but poor resemblance is obtained at higher
      wavelengths. We are however confident that improvement of experimental conditions
      and theoretical description will allow that in the near future, external
      reflection circular dichroism (CD) can be a valuable tool that complements the
      application of external reflection infrared spectroscopy to study interfacial
      systems.

PMID- 12511105
TI  - Vibrational analysis of substituted phenols: part II. Transferability of valence
      force constants.
AB  - A zero-order normal coordinate analysis was made for the in-plane and out-of
      plane vibrations of 2,6-dimethylphenol, 2,3-dimethylphenol, 3,5-dimethylphenol,
      2,6-dichloro-4-nitrophenol, 2,4-dichloro-6-nitrophenol, 3-chloro-4-hydroxy-5
      methoxybenzaldehyde, 3-bromo-4-hydroxy-5-methoxybenzaldehyde and 3-iodo-4-hydroxy
      5-methoxybenzaldehyde and for the in-plane vibrations of 2-amino-4-nitrophenol by
      transferring the force constants obtained beforehand. The transferability of the
      force constants was demonstrated by the good agreement between the observed and
      calculated frequencies. On the basis of calculated potential energy distributions
      and eigenvectors, several assignments suggested by earlier workers have been
      revised.

PMID- 12511106
TI  - Interaction of cyanine dyes with nucleic acids: XXVI. Intercalation of the
      trimethine cyanine dye cyan 2 into double-stranded DNA: study by spectral
      luminescence methods.
AB  - The interaction between double-stranded (ds) DNA and the cyanine dye Cyan 2 has
      been studied with spectral luminescence methods. Binding constant values have
      been determined by fluorescence titration and dye distribution in the two-phase
      system ethyl acetate-water (3.6 x 10(4) and 1.5 x 10(4) M(-1), respectively).
      Cyan 2 exhibits a small specificity for guanine-cytosine (GC) sequences in total
      DNA and synthetic polydeoxynucleotides poly(dA/dT) and poly(dGdC/dGdC). The DNA
      complexes with Cyan 2 are stable at high-ionic strength solution when NaCl is
      added. The dye molecule complexed with DNA is apparently shielded from the
      anionic quencher--iodide ion. The negative linear dichroism of the visible
      absorption band of aligned Cyan 2-DNA complexes indicates that the bound dye lies
      almost perpendicularly to the DNA helix axis. The linear dichroism of the
      absorption band at 260 nm suggests a considerable change in the DNA B-form. The
      results are consistent with an intercalative binding interaction between Cyan 2
      and ds DNA.

PMID- 12511107
TI  - Inhibitory activity of minor polyphenolic and nonpolyphenolic constituents of
      olive oil against in vitro low-density lipoprotein oxidation.
AB  - The minor polyphenolic and nonpolyphenolic constituents of olive oil were
      examined, in various doses, against copper ion-induced low-density lipoprotein
      (LDL) oxidation and were found, in optimal doses (final concentration, 10 microM
      or 20 microM), to have remarkable biological activity, contributing to that
      previously reported for the major phenolic compounds. The main phytosterols, beta
      sitosterol, campesterol, and stigmasterol, were found to have 43.8%, 37.3%, and
      33.4% LDL mean protection (MP) activity, respectively, while free cholesterol
      exhibited 43.2% MP. The triterpenoid derivative compounds, ursolic acid, uvaol,
      and oleanolic acid, had similar MP activities of 50.5%, 46.8%, and 46.0%,
      respectively. Tocopherol (Toc) isomers exhibited an increasing effect in the
      following order: alpha-Toc (33.6%) < beta-Toc (36.1%) < gamma-Toc (42.9%) < delta
      Toc (46.0%). The flavonoid polyphenols, quercetin, luteolin, and rutin, exhibited
      the highest activities--46.8%, 49.5%, and 53.7% MP, respectively, comparable to
      the 49.0% MP activity found for oleuropein. These findings indicate the relative
      independence of LDL protection activity in regard to structural differences among
      the involved compounds. A relation to the Mediterranean diet is also
      demonstrated.

PMID- 12511108
TI  - Antioxidant capability and efficacy of Mega-H silica hydride, an antioxidant
      dietary supplement, by in vitro cellular analysis using photosensitization and
      fluorescence detection.
AB  - Treatment of Chinese hamster ovary and mouse hybridoma cells with Mega-H brand
      silica hydride, a marketed antioxidant, after photosensitization with singlet
      oxygen and hydroxyl/superoxide reactive oxygen species through the use of rose
      bengal diacetate and malachite green resulted in an effective method of reducing
      free radical activity by more than 96% against singlet oxygen species and more
      than 86% for hydroxyl and superoxide free radicals with the dosage recommended by
      the manufacturer. The analysis used a combinational spectrafluorometric technique
      to determine cell viability and cytotoxicity through the mechanism of
      intracellular esterase activity and plasma membrane integrity. Photosensitized
      controls not treated with silica hydride showed less than 1% viability under the
      same conditions. The reduction of the introduced free radicals and singlet oxygen
      species and the consequent high levels of cell viability may be the result of
      effective and efficient antioxidant and radical scavenging properties of silica
      hydride.

PMID- 12511109
TI  - Effect of cocoa flavanols and their related oligomers on the secretion of
      interleukin-5 in peripheral blood mononuclear cells.
AB  - We previously showed that flavanols and their related oligomers (FLO) isolated
      from cocoa can have immunomodulatory effects on production of the cytokines
      interleukin-1beta (IL-1beta), IL-2, and IL-4. In the present study, we examined
      whether selected FLO fractions isolated from cocoa (monomer through decamer)
      modulate IL-5 protein secretion from resting and phytohemagglutinin (PHA)
      stimulated peripheral blood mononuclear cells (PBMC). Although FLO fractions were
      unstimulatory for IL-5 secretion in resting cells, PHA-induced IL-5 release from
      PBMC was markedly affected by certain FLO fractions. The monomeric and small
      oligomeric (dimer and trimer) fractions enhanced PHA stimulation by 50%, 54%, and
      43%, respectively. In contrast, the larger oligomeric fractions (hexamer through
      decamer) inhibited IL-5 release in the range of 18% to 39%; the tetramer and
      pentamer showed intermediate effects. The increment in IL-5 suggests that FLO may
      preferentially stimulate immunoglobulin A. We suggest that in the oral cavity
      this could result in reduction in the risk for dental caries and periodontal
      disease. This work offers additional data for consideration of the health
      benefits of dietary FLO from a variety of foods, including those benefits
      associated specifically with consumption of some cocoas and chocolates.

PMID- 12511110
TI  - Tagatose, the new GRAS sweetener and health product.
AB  - Tagatose, a low-calorie, full-bulk natural sugar, has just attained GRAS
      (Generally Recognized As Safe) status under U.S. Food and Drug Administration
      (FDA) regulations, thereby permitting its use as a sweetener in foods and
      beverages. This paper presents all current aspects of tagatose with respect to
      demonstrated food and beverage applications and the potential health and medical
      benefits of this unique substance. Summarized studies are referenced to detailed
      peer-reviewed papers. The safety studies followed the recommendations in the FDA
      "Red Book." Results were submitted to an Expert Panel for determination of GRAS
      status under FDA regulation. Small phase 2 clinical trials showed tagatose to be
      effective in treating type 2 diabetes. The results, buttressed by the references
      cited, support the efficacy of the various applications disclosed for tagatose.
      Tagatose has been found to be safe and efficacious for use as a low-calorie, full
      bulk sweetener in a wide variety of foods, beverages, health foods, and dietary
      supplements. It fills broad, heretofore unmet needs for a low-calorie sweetener
      in products in which the bulk of sugar is important, such as chocolates, chewing
      gum, cakes, ice cream, and frosted cereals. Its synergism with high-intensity
      sweeteners also makes it useful in sodas. Various health and medical benefits are
      indicated, including the treatment of type 2 diabetes, hyperglycemia, anemia, and
      hemophilia and the improvement of fetal development.

PMID- 12511111
TI  - Effects of chard (Beta vulgaris L. var. cicla) extract on oxidative injury in the
      aorta and heart of streptozotocin-diabetic rats.
AB  - In diabetes mellitus, increased free radical formation raises the incidence of
      atherosclerosis and cardiovascular diseases. Regardless of the type of diabetes,
      the objective of the therapy is to achieve normoglycemia and to prevent or delay
      the complications. Chard (Beta vulgaris L. var. cicla) is used as a hypoglycemic
      agent by diabetic patients in Turkey. The aim of this study was to investigate
      the effect of feeding chard on diabetes-induced free radical-mediated injury in
      rat aorta and heart tissues. Female Swiss albino rats were randomly divided into
      four groups: control, diabetic, chard, and diabetic + chard. Rats were subjected
      to intraperitoneal streptozotocin (STZ, 65 mg/kg) to induce diabetes. Chard
      extract (2 g/kg) was given for 28 days beginning on the 14th day of the study.
      Aorta and heart tissue lipid peroxidation and glutathione levels as well as blood
      glucose levels were determined. The results of the present study indicate that
      lipid peroxidation was increased and glutathione levels were decreased in both
      aorta and heart tissue of the diabetic rats. However, treatment with chard
      extract reversed the effects of diabetes on blood glucose and tissue lipid
      peroxidation and glutathione levels.

PMID- 12511112
TI  - Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male
      rats.
AB  - This work describes the potential usefulness of bioflavonoids for countering the
      deleterious effects of aging on male sexuality in 2-year-old rats. A flavone
      chrysin from Passiflora caerulea Linn. and a benzoflavone moiety (BZF) recently
      isolated from Passiflora incarnata Linn. were administered to 2-year-old male
      rats for a period of 30 days. After cessation of these treatments, there was a
      significant improvement in overall sexual functions in the rats given
      bioflavonoids, compared with control rats. The rats receiving chrysin (1 mg/kg)
      and BZF (10 mg/kg) exhibited increased libido when they were allowed to interact
      with nonestrous female rats. Additionally, both treated groups had increased
      sperm count, greater fertilization potential, and greater litter size when they
      were allowed to interact with proven proestrous female rats of a similar strain.
      BZF was more potent than chrysin as an antiaromatase agent and exhibited better
      effects on the sexual system of the 2-year-old male rats. Plant flavonoids have
      great potential for clinical and therapeutic applications against the
      physiological and biochemical effects of aging.

PMID- 12511113
TI  - Fluvastatin reduced major adverse cardiac outcomes after first percutaneous
      coronary intervention.

PMID- 12511114
TI  - Simvastatin reduced mortality and vascular events in high-risk patients.

PMID- 12511115
TI  - Antioxidant vitamins did not reduce death, vascular events, or cancer in high
      risk patients.

PMID- 12511116
TI  - Review: beta-blockers increase fatigue and sexual dysfunction but not depression
      after myocardial infarction.

PMID- 12511117
TI  - Review: Sildenafil improves erectile dysfunction and is well tolerated.

PMID- 12511118
TI  - Estrogen plus progestin was not effective for long-term secondary prevention of
      coronary heart disease in postmenopausal women.

PMID- 12511119
TI  - Long-term estrogen plus progestin increased venous thromboembolism and biliary
      tract surgery in postmenopausal women.

PMID- 12511120
TI  - Biphasic waveform shocks were effective and efficient for cardioversion of atrial
      fibrillation.

PMID- 12511121
TI  - Coumadin alone or aspirin plus coumadin reduced coronary events and death after
      acute myocardial infarction or unstable angina.

PMID- 12511122
TI  - Oral vitamin K reversed warfarin-associated coagulopathy faster than subcutaneous
      vitamin K.

PMID- 12511123
TI  - Lansoprazole reduced recurrence of ulcer complications in long-term use of low
      dose aspirin.

PMID- 12511124
TI  - Review: angiotensin II receptor antagonists prevent headache in patients with
      mild-to-moderate hypertension.

PMID- 12511126
TI  - Review: several drugs are efficacious for symptomatic treatment of Parkinson
      disease.

PMID- 12511125
TI  - Involving patients with type 2 diabetes, hypertension, and hyperlipidemia in
      disease management improved outcomes.

PMID- 12511127
TI  - Review: flumazenil leads to clinical and electroencephalographic improvement in
      hepatic encephalopathy in patients with cirrhosis.

PMID- 12511128
TI  - Noninvasive Helicobacter pylori testing was as effective as endoscopy for
      managing dyspepsia.

PMID- 12511129
TI  - Helicobacter pylori eradication improved dyspepsia symptoms.

PMID- 12511130
TI  - Review: inhaled corticosteroids reduce hospital admissions in acute asthma.

PMID- 12511132
TI  - Hylan G-F 20 was safe and effective in knee osteoarthritis and had a relatively
      low cost-utility ratio.

PMID- 12511131
TI  - Etanercept was effective and safe for ankylosing spondylitis.

PMID- 12511133
TI  - Review: S-adenosylmethionine treats osteoarthritis as effectively as nonsteroidal
      anti-inflammatory drugs with fewer adverse effects.

PMID- 12511134
TI  - Botulinum toxin A injections improved wrist and finger spasticity after stroke.

PMID- 12511135
TI  - BNP levels had high sensitivity but moderate specificity for detecting congestive
      heart failure in the emergency department.

PMID- 12511136
TI  - Review: ELISA D-dimer is sensitive but not specific in diagnosing pulmonary
      embolism in an ambulatory clinical setting.

PMID- 12511137
TI  - The Memory Impairment Screen more accurately screened for Alzheimer disease than
      the 3-word memory test in older adults.

PMID- 12511138
TI  - Review: Beta-blockers increase fatigue and sexual dysfunction but not depression
      after myocardial infarction.

PMID- 12511139
TI  - Practice corner: taking evidence in hand.

PMID- 12511142
TI  - Mayo Clinic general surgery training legacy.

PMID- 12511143
TI  - Hypertonic saline infusion for pulmonary injury due to ischemia-reperfusion.
AB  - HYPOTHESIS: Inhibition of neutrophil-endothelial cell interactions by hypertonic
      saline (HTS) may confer protection against organ injury in states of immunologic
      disarray. This study tested the hypothesis that infusion of HTS modulates the
      development of end-organ injury in a model of lower-torso ischemia-reperfusion
      injury. DESIGN: Ischemia-reperfusion injury was induced in 30 male Sprague-Dawley
      rats by infrarenal aortic cross-clamp for 30 minutes, followed by reperfusion for
      2 hours. At 0 and 60 minutes of reperfusion, intravenous HTS (7.5% sodium
      chloride, 4 mL/kg) was administered to 6 rats each, and another 12 received
      either 4 or 30 mL/kg of isotonic sodium chloride solution. Six rats received HTS,
      4 mL/kg, before ischemia. At 2 hours, we assessed liver function, pulmonary
      injury, neutrophil infiltration (myeloperoxidase activity), endothelial
      permeability (bronchoalveolar lavage and wet-dry weight ratios), and
      proinflammatory cytokine levels (tumor necrosis factor alpha and interleukin 6).
      RESULTS: Infusion with HTS before or after ischemia significantly reduced end
      organ injury. Histopathologic pulmonary injury scores were markedly attenuated in
      the HTS group (5.82 +/- 1.3) and the HTS pretreated group (4.91 +/- 1.6) compared
      with the isotonic sodium chloride solution groups (8.54 +/- 1.1) (P =.04).
      Pulmonary neutrophil sequestration (2.07 +/- 0.23) and increased endothelial
      permeability (4.68 +/- 0.44) were manifest in animals resuscitated with isotonic
      sodium chloride solution compared with HTS treatment (1.54 +/- 0.19 [P =.04] and
      2.06 +/- 0.26 [P =.02]) and pretreatment (1.18 +/- 0.12 [P =.04] and 1.25 +/-
      0.07 [P =.002]). In addition, a significant reduction in serum tumor necrosis
      factor alpha (P =.04) and interleukin 6 (P =.048) levels was observed, whereas
      HTS resuscitation attenuated the upsurge in aspartate transaminase (P =.03) and
      alanine transaminase levels (P =.047). CONCLUSIONS: Resuscitation with HTS
      attenuates the pulmonary edema and tissue injury due to lower-torso ischemia
      reperfusion and maintains a more benign immunologic profile.

PMID- 12511144
TI  - Isolated limb perfusion: distinct tourniquet and tumor necrosis factor effects on
      the early hemodynamic response.
AB  - HYPOTHESIS: Recent evidence indicates that tumor response rates after isolated
      limb perfusion (ILP) are improved when tumor necrosis factor (TNF) is added to
      the locoregional perfusion of high doses of chemotherapy. Other factors, related
      to the patient or the ILP procedure, may interfere with the specific role of TNF
      in the early hemodynamic response after ILP with TNF and high-dose chemotherapy.
      DESIGN: Case-control study. SETTING: Tertiary care university hospital. PATIENTS:
      Thirty-eight patients with a locoregionally advanced tumor of a limb treated by
      ILP with TNF and high-dose chemotherapy (TNF group) were compared with 31 similar
      patients treated by ILP with high-dose chemotherapy alone (non-TNF group).
      INTERVENTIONS: Swan-Ganz catheter hemodynamic recordings, patients' treatment
      data collection, and TNF and interleukin 6 plasma level measurements at regular
      intervals during the first 36 hours following ILP. MAIN OUTCOME MEASURES:
      Hemodynamic profile and total fluid and catecholamine administration. RESULTS: In
      the TNF group, significant changes were observed (P<.006): the mean arterial
      pressure and the systemic vascular resistance index decreased, and the
      temperature, heart rate, and cardiac index increased. These hemodynamic
      alterations started when the ILP tourniquet was released (ie, when or shortly
      after the systemic TNF levels were the highest). The minimal mean arterial
      pressure, the minimal systemic vascular resistance index, the maximal cardiac
      index, the intensive care unit stay, and the interleukin 6 maximal systemic
      levels were significantly (P<.001 for all) correlated to the log(10) of the
      systemic TNF level. In the non-TNF group, only a brief decrease in the blood
      pressure following tourniquet release and an increase in the temperature and in
      the heart rate were statistically significant (P<.006). Despite significantly
      more fluid and catecholamine administration in the TNF group, the mean arterial
      pressure and the systemic vascular resistance index were significantly (P<.001)
      lower than in the non-TNF group. CONCLUSIONS: Release of the tourniquet induces a
      blood pressure decrease that lasts less than 1 hour in the absence of TNF and
      that is distinct from the septic shock-like hemodynamic profile following TNF
      administration. The systemic TNF levels are correlated to this hemodynamic
      response, which can be observed even at low TNF levels.

PMID- 12511145
TI  - Factors predicting survival after intraperitoneal hyperthermic chemotherapy with
      mitomycin C after cytoreductive surgery for patients with peritoneal
      carcinomatosis.
AB  - HYPOTHESIS: Certain clinicopathologic factors predict improved survival after
      cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for
      peritoneal carcinomatosis. DESIGN: Prospective clinical trial. SETTING: Surgical
      oncology service at a university academic hospital. PATIENTS: A population of 109
      consecutive patients with peritoneal carcinomatosis treated between December 1991
      and November 1997. INTERVENTION: All patients underwent resection of gross
      disease followed by 2-hour intraoperative perfusion of mitomycin C (20-40 mg)
      into the peritoneal cavity at a temperature of 40.5 degrees C. MAIN OUTCOME
      MEASURES: Clinicopathologic factors that independently predicted improved overall
      survival rates. RESULTS: Overall survival at 1 and 3 years was 61% and 33%,
      respectively. With median follow-up of 52 months, median overall survival was 16
      months. Four factors were significant independent predictors of improved survival
      by multivariate analysis: nonadenocarcinoma histologic features (P =.001), the
      appendix as a primary site (P =.003), the absence of hepatic parenchymal
      metastases (P =.01), and complete resection of all gross disease (R1/0 resection)
      (P<.001). Patients with an R1/0 resection vs an incomplete resection of gross
      disease (R2 resection) had 3-year overall survival of 68% vs 21% (P<.001).
      CONCLUSIONS: Patients with peritoneal carcinomatosis have a uniformly poor
      prognosis. However, in select patients, the natural history of this disease
      condition may be altered by using the multimodality approach of cytoreductive
      surgery and intraperitoneal hyperthermic chemotherapy. These results require
      confirmation in prospective randomized studies.

PMID- 12511146
TI  - Decrease of collagen deposition in wound repair in type 1 diabetes independent of
      glycemic control.
AB  - HYPOTHESIS: Type 1 and type 2 diabetes mellitus and glycemic control influence
      wound healing in humans. DESIGN: Experimental study using a human wound-healing
      model. SETTING: Collaboration among a multidisciplinary wound-healing department,
      department of medicine, and research laboratories. PATIENTS, CONTROL SUBJECTS,
      AND METHODS: In 34 patients with type 1 (insulin-dependent) and 25 with type 2
      (non-insulin-dependent) diabetes and 5 nondiabetic control subjects matched with
      the type 2 diabetic patients, wound-healing capacity was determined as
      subcutaneous accumulation of collagen measured as hydroxyproline. Two expanded
      polytetrafluoroethylene tubes were implanted and removed 10 days later. The
      hydroxyproline level was determined by means of high-performance liquid
      chromatography; the collagenase activity, by using a radiolabeled collagen
      substrate. Proliferation of fibroblasts cultured from the wounds was studied in
      patient groups. RESULTS: The deposition of hydroxyproline decreased by 40% (P
      =.03) in type 1 compared with type 2 diabetes (median, 0.70 vs 1.16 nmol/mg;
      interquartile range, 0.48-1.04 vs 0.56-1.63 nmol/mg), which in turn did not
      differ significantly from that of controls (median, 1.35 nmol/mg; interquartile
      range, 0.72-1.88 nmol/mg). The decreased collagen deposition in type 1 diabetes
      was not caused by increased collagenase activity. The deposition of
      hydroxyproline did not correlate significantly (r(s) = 0.07; P =.63) with
      glycosylated hemoglobin levels in either diabetic group. Fibroblast growth was
      also decreased in type 1 compared with type 2 diabetic patients and controls.
      CONCLUSIONS: Collagen deposition in acute wounds is impaired in type 1 diabetes,
      possibly due to a decreased fibroblast proliferation. In type 2 diabetes,
      collagen deposition is normal. Glycemic control does not influence collagen
      deposition in acute wound repair in type 1 or in type 2 diabetes mellitus.

PMID- 12511147
TI  - Postoperative complication rates after hepatic resection in Maryland hospitals.
AB  - HYPOTHESIS: High-volume centers provide superior quality care and therefore have
      a lower incidence of postoperative complications. DESIGN: Observational statewide
      administrative database. SETTING: State of Maryland, nonfederal acute-care
      hospital (n = 52), performing liver resection (n = 35). PATIENTS: All patients
      discharged after undergoing hepatic resection from 1994 to 1998 (N = 569). MAIN
      OUTCOME MEASURES: Two sequential analyses using multiple logistic regression of
      in-hospital mortality were performed to determine the relative importance of
      preoperative case-mix and postoperative complications. RESULTS: The overall in
      hospital mortality rate was 4.8% and was significantly lower in high-volume
      hospitals (2.8%) than in low-volume hospitals (10.2%) (P<.001). After adjusting
      for case-mix in the multivariate analysis, low hospital volume was associated
      with a 3-fold increase in mortality (odds ratio, 3.1; 95% confidence interval
      [CI], 1.2-7.6; P =.02). Having surgery at a low-volume hospital was associated
      with increased rates of several postoperative complications: reintubation
      (relative risk [RR], 2.5; 95% CI, 1.8-3.4), pulmonary failure (RR, 2.3; 95% CI,
      1.6-3.5), pneumonia (RR, 0.35; 95% CI, 1.0-5.6), acute renal failure (RR, 2.0;
      95% CI, 1.1-3.7), acute myocardial infarction (RR, 2.6; 95% CI, 1.2-5.9), and
      aspiration (RR, 1.4; 95% CI, 0.9-2.0). When considering all other factors using
      statistical methods, hospital volume was no longer associated with mortality.
      CONCLUSIONS: Patients who undergo hepatic resection at low-volume hospitals are
      at a higher risk of postoperative complications and death than those who have the
      same operation at high-volume hospitals. The empirical difference between
      outcomes at high- and low-volume hospitals seems to be due to a variation in
      postoperative complications.

PMID- 12511148
TI  - Patient outcomes in academic medical centers: influence of fellowship programs
      and in-house on-call attending surgeon.
AB  - BACKGROUND: There are very few data on characteristics or policies that improve
      patient outcomes in academic medical institutions. We were interested in 2 such
      policies or characteristics that are commonly implemented in academic centers: an
      in-house on-call attending physician policy and the existence of postgraduate
      medical education. HYPOTHESIS: An in-house attending surgeon on-call policy and
      the presence of trauma and critical care fellowship programs improve outcomes of
      critically injured patients. DESIGN: Multicenter cohort study. Two cohorts were
      analyzed: blunt trauma (n = 601; mortality, 16.0%) and penetrating abdominal
      trauma (n = 503; mortality, 7.5%). SETTING: Thirty-one academic level I trauma
      centers, 10 (32.3%) with in-house on-call policy and 11 (35.5%) with fellowship
      programs. MAIN OUTCOME MEASURES: Mortality, hospital length of stay, and
      intensive care unit length of stay. RESULTS: In-house on-call surgeon policy had
      no impact on mortality or length of hospital or intensive care unit stay for
      either the blunt or penetrating trauma cohort. However, the presence of
      fellowship programs was associated with a significant decrease in blunt trauma
      mortality (odds ratio, 0.4; 95% confidence interval [CI], 0.1-0.8) and a decrease
      in length of intensive care unit stay (mean difference, 4.7 days; 95% CI, 0.6-8.8
      days) and hospital stay (mean difference, 3.2 days; 95% CI, 0.6-5.9 days). There
      were no significant effects of fellowship programs on penetrating trauma
      outcomes. CONCLUSIONS: An in-house on-call attending surgeon policy is not
      associated with improved outcomes. In contrast, presence of a trauma and surgical
      critical care fellowship program, a potential surrogate marker for an institution
      that is committed to this specialty interest, is associated with improved
      outcomes for critically injured patients. An investment in advanced postgraduate
      medical education has potential benefits in patient care and outcomes.

PMID- 12511150
TI  - Axillary dissection is not required for all patients with breast cancer and
      positive sentinel nodes.
AB  - HYPOTHESIS: Sentinel node (SN) biopsy for breast cancer enhances staging
      sensitivity, often demonstrating only micrometastases (<2 mm) or isolated,
      keratin-positive cells. When SN metastasis is present, the value of additional
      axillary dissection is unclear and not all patients benefit from axillary lymph
      node dissection (ALND). DESIGN: Prospective cohort study, median 32-month follow
      up. SETTING: Multidisciplinary breast cancer centers. PATIENTS: Forty-six women
      having SN metastases diagnosed between May 1, 1996, and September 1, 2001, who
      refused ALND or were recommended to omit ALND owing to serious comorbid
      conditions. INTERVENTIONS: Isosulfan blue dye-directed SN biopsy. Axillary lymph
      node dissection was not performed. Standard breast irradiation was given.
      Adjuvant systemic therapy was provided as determined by an oncologist. Interval
      clinical evaluation was performed. MAIN OUTCOME MEASURE: Axillary and systemic
      failure rates. RESULTS: Mean patient age was 61.6 years (age range, 36-92 years).
      Mean tumor size was 1.65 cm (range, 0.4-5.5 cm). Thirty-five (76%) of 46 tumors
      were ductal carcinomas and 39 (87%) of 45 were estrogen receptor-positive. A mean
      of 2.6 SNs were identified (median, 2; range, 1-7). Thirty-nine patients (85%)
      had a single positive SN; the remaining 7 patients (15%) had 2 positive SNs.
      Seven patients (15%) had macrometastases (>2 mm); 16 (35%) had micrometastases
      (<2 mm); and 23 (50%) had cellular metastases. Only 16 positive SNs (35%) were
      seen on hematoxylin-eosin staining, while 30 SNs (65%) had positive
      immunohistochemical staining. There have been no axillary recurrences. One
      patient (2%) developed distant metastases during follow-up (range, 4-61 months).
      CONCLUSIONS: Patients with SN metastases who did not have ALND had a low
      incidence of regional failure. To confirm this observation, we suggest that
      patients with SN metastases are ideal candidates for trials evaluating the
      necessity of ALND.

PMID- 12511151
TI  - Presentation of Degos syndrome as acute small-bowel perforation.
AB  - Malignant atrophic papulosis is an uncommon vasculopathy affecting multiple
      systems and frequently associated with a poor prognosis. We describe a 56-year
      old patient with this rare disorder whose death was the result of intestinal
      involvement. Clinical diagnostic features of malignant atrophic papulosis as well
      as the main therapeutic approaches suggested in the literature are presented
      herein.

PMID- 12511152
TI  - Trials and tribulations: current challenges in conducting clinical trials.
AB  - Randomized controlled trials are the gold standard for the evaluation of new
      therapies and surgical procedures and as such require strict attention to study
      design and statistical analysis. There are, however, multiple challenges in
      conducting a well-designed clinical trial. This article describes the
      difficulties encountered at a single institution participating in a multicenter
      drug study and reviews the challenges involved in developing a high-quality
      randomized controlled study.

PMID- 12511153
TI  - High isotope counts and sentinel node positivity in patients with melanoma.
AB  - BACKGROUND: Radioisotope mapping is an essential technical component of sentinel
      lymph node (SLN) biopsy, and most authors define success by an arbitrary
      threshold SLN-background ratio. HYPOTHESIS: Few studies have examined the degree
      to which the relative level of SLN counts correlates with the presence of
      metastasis. Having removed the SLN with the highest counts, there are no data
      suggesting how far the surgeon should persist in removing additional SLNs that
      contain much lower levels of isotope. METHODS: We performed 134 SLN biopsy
      procedures in 132 patients with melanoma. Successful isotope localization was
      defined using an SLN/"hottest" SLN ratio; we defined an SLN as any node
      containing counts at least 10% of that of the hottest SLN. RESULTS: Of 83
      patients with more than 1 SLN site identified, 21 (25%) had SLNs that contained
      metastasis. In 17 (81%) of these cases, the SLN with the highest countcontained
      tumor, but in 4 (19%) it was benign. Among these 4 patients, the counts of the
      hottest benign SLNs exceeded those of SLNs positive for metastasis on
      histological examination by a ratio of at least 10:1, and the counts of the
      positive SLNs were less than 4:1 of those of the background counts or the
      presence of blue dye failed to identify the positive SLN. No optimum ratio of
      SLN/SLN or SLN/background counts identified the positive SLN in all cases.
      CONCLUSIONS: Although the SLN with the highest counts contained metastasis in 81%
      of patients with malignant melanoma and multiple SLNs, neither a relatively high
      isotope count nor the presence of blue dye consistently predicted SLN positivity.
      For maximum accuracy, SLN biopsy requires the removal of all nodes containing
      isotope regardless of the relative magnitude of counts and the concurrent use of
      blue dye to salvage those procedures in which isotope mapping fails.

PMID- 12511155
TI  - The spectrum of pneumatosis intestinalis.
AB  - HYPOTHESIS: A review of the spectrum of illness associated with pneumatosis
      intestinalis enables us to identify the probable causes of, the best diagnostic
      approaches to, and the most appropriate treatments for this condition. DATA
      SOURCES: A review of all published material in the English language regarding
      pneumatosis intestinalis was conducted using the PubMed and MEDLINE databases.
      Any relevant work referenced in those articles and not previously found or
      published before the limit of the search engine was also retrieved and reviewed.
      STUDY SELECTION: There were no exclusion criteria for published information
      relevant to the topic. All of the studies cited in the present review make a
      point that contributes to the portrayal of this condition. In circumstances in
      which the same point was made in several different studies, not all were cited
      herein. DATA EXTRACTION: All published material on pneumatosis intestinalis was
      considered. Information was extracted for preferentially selected ideas and
      theories supported in multiple studies. DATA SYNTHESIS: The collected information
      was organized by theory. CONCLUSIONS: Mucosal integrity, intraluminal pressure,
      bacterial flora, and intraluminal gas all interact in the formation of
      pneumatosis intestinalis. Radiography and computed tomography are the best
      diagnostic tests. Nonoperative management should be pursued in most patients, and
      underlying illnesses should be treated. When acute complications appear, such as
      perforation, peritonitis, and necrotic bowel, surgery is indicated.

PMID- 12511156
TI  - Laparoscopic vs conventional ileocolectomy for primary Crohn disease.
AB  - HYPOTHESIS: Laparoscopic ileocolectomy can reduce the length of hospital stay and
      hospital charges compared with conventional surgery in the treatment of primary
      Crohn disease. DESIGN: Nonrandomized, comparative, retrospective analysis of a
      prospective database. SETTING: University hospital tertiary care center for
      inflammatory bowel disease. PATIENTS: Forty patients, 20 in the laparoscopic
      group (group A) and 20 in the conventional group (group B). INTERVENTION: From
      July 1, 1996, to June 30, 2001, we collected data on the following demographic
      clinical end points: age, sex, duration of disease, preoperative medical
      treatment, previous abdominal surgery, procedure performed, conversions to open
      surgery, operating time, number of trocars used, size of incision, blood loss,
      time to resolution of ileus, time to starting solid food diet, duration of
      hospital stay, hospital charges, morbidity, and mortality. MAIN OUTCOME MEASURES:
      Surgical results, length of hospital stay, hospital charges, and recurrences.
      RESULTS: The mean age of the patients was 34.7 years (range, 20-68 years) in
      group A vs 40.0 years (range, 18-75 years) in group B. The male-female ratio was
      1:2 in group A vs 1:1 in group B. The morbidity was 5% in group B. There was no
      mortality. Operating time was longer in group A (mean, 145.0 minutes; range, 45
      270 minutes) compared with group B (mean, 133.5 minutes; range, 98-177 minutes)
      (P =.36). Blood loss was significantly higher in group B (mean, 265.5 mL; range,
      100-400 mL) compared with group A (77.2 mL; range, 25-350 mL) (P<.001). Also, the
      size of the incision was significantly longer in group B (mean, 13.5 cm; range, 8
      18 cm) compared with group A (mean, 5.5 cm; range, 3-12 cm) (P<.001). Bowel
      function returned more quickly in the laparoscopic group vs the conventional
      group in terms of return of bowel movements (1.70 vs 2.63 days) (P<.001) and
      resumption of a regular diet (1.35 vs 2.73 days) (P<.001). The mean length of
      stay was significantly shorter in the laparoscopic group (4.25 days) vs the
      conventional group (8.25 days) (P<.001). The mean hospital charges were US $9614
      in group A vs US $17 079 in group B (P<.05). The mean follow-up was 17.2 months
      in group A (range, 2.3-59.9 months) vs 18.7 months in group B (range, 1.0-37.5
      months). CONCLUSIONS: Laparoscopic-assisted ileocolectomy for primary Crohn
      disease of the terminal ileum and/or cecum is safe and successful in most cases.
      Laparoscopic surgery for Crohn disease should be considered as the preferred
      operative approach for primary resections.

PMID- 12511157
TI  - Adenocarcinoma of the third and fourth portions of the duodenum: results of
      surgical treatment.
AB  - HYPOTHESIS: To verify the adequacy of duodenal segmentectomy after intestinal
      derotation in the treatment of primary adenocarcinoma of the third and fourth
      portions of the duodenum. DESIGN: A retrospective review of the surgical
      management of patients who underwent derotation of the third and fourth portions
      of the duodenum was undertaken to determine long-term outcome. SETTING:
      Departments of surgery in 3 university hospitals. PATIENTS: Between January 1,
      1980, and December 31, 2000, 47 patients with primary adenocarcinoma of the third
      and fourth portions of the duodenum were surgically treated at 3 different
      institutions. MAIN OUTCOME MEASURES: Details of primary surgery were abstracted
      from clinical records of the original hospital referral. Postoperative clinical
      course and long-term outcome were evaluated by a review of the hospital records
      and follow-up. RESULTS: The results of a barium swallow test series was positive
      in 38 cases (80.8%) and esophagogastroduodenoscopy was primarily diagnostic in 30
      patients (63.8%). In all cases duodenal segmentectomy was attempted. Twenty-two
      patients underwent palliative gastrojejunal bypass and in 9 patients
      pancreaticoduodenectomy was performed. In 16 cases duodenal segmentectomy was
      performed after intestinal derotation. Anastomoses were performed manually in all
      cases. Fifteen of the resected patients died of recurrent disease. A median (SD)
      disease-free survival of 36 (23.6) months (range, 6-85 months) was observed. The
      median (SD) overall survival was 37.5 (23.9) months (range, 11-85 months), the
      overall 5-year survival rate was 23% (11 patients), and the actuarial 5-year
      survival rate was 51% (24 patients). CONCLUSIONS: Duodenal segmentectomy
      associated with intestinal derotation was shown to be a straightforward, safe
      procedure for the treatment of the primary adenocarcinoma of the third and fourth
      portions of the duodenum. This surgical procedure should be preferred to
      pancreaticoduodenectomy because it is associated with negligible rates of
      morbidity and mortality, while allowing for satisfactory margin clearance and
      adequate lymphadenectomy.

PMID- 12511158
TI  - Hepatic resection for combined hepatocellular and cholangiocarcinoma.
AB  - HYPOTHESIS: Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC)
      is an uncommon form of primary liver cancer with features of hepatocellular and
      biliary epithelial differentiation. The clinical significance of this disease
      entity is poorly understood. The aim of the present study was to determine the
      operative and survival outcomes of patients with HCC-CC who underwent hepatic
      resection. DESIGN: Retrospective study. SETTING: Tertiary referral center.
      PATIENTS: The study comprised 12 patients (aged 28-72 years) with HCC-CC (HCC-CC
      group) who underwent hepatic resection between January 1, 1991, and December 31,
      2000. The diagnosis was based on a combination of histological,
      immunohistochemical, and, if necessary, electron microscopic examinations of the
      resected specimen. MAIN OUTCOME MEASURES: Clinicopathological data and operative
      and survival outcomes of the HCC-CC group were compared with those of 476
      patients with HCC (HCC group) and 25 patients with intrahepatic CC (CC group) who
      underwent hepatic resection during the study period. RESULTS: Ten patients (83%)
      in the HCC-CC group underwent major hepatic resection. The operative morbidity
      and mortality were 17% (2 of 12 patients) and 0%, respectively. The
      clinicopathological variables of the HCC-CC group resembled those of the HCC
      group more closely than those of the CC group. The incidence of positive
      hepatitis B serologic test results in the HCC-CC group (7 [58%] of 12 patients)
      was intermediate between that of the HCC group (392 [82%] of 476 patients) and
      that of the CC group (5 [20%] of 25 patients) (P<.001). Underlying chronic liver
      disease was significantly less common in the CC group (5 [20%] of 25 patients)
      than in either the HCC-CC group (9 [75%] of 12 patients) or the HCC group (421
      [88%] of 476 patients) (P<.001). After hepatic resection, the median disease-free
      survival of the HCC-CC, HCC, and CC groups was 10, 18, and 24 months,
      respectively (P =.44). The overall median survival was shortest in the HCC-CC
      group (17 months) and was not significantly different from that of the CC group
      (26 months) (P =.38), but was significantly worse than that of the HCC group (52
      months) (P =.02). CONCLUSIONS: Although the clinicopathological variables of
      patients with HCC-CC were most similar to those of patients with HCC, patients
      with HCC-CC had a significantly worse survival outcome after hepatic resection
      when compared with patients with HCC. Further studies on postoperative adjuvant
      therapy and multimodality treatment for recurrent disease are required to prolong
      the survival of these patients.

PMID- 12511159
TI  - Breast cancer in pregnancy: a literature review.
AB  - HYPOTHESIS: Breast cancer in pregnancy will increase as more women postpone
      childbearing until later in life. OBJECTIVE: To review the literature on
      diagnosis, staging, treatment, and prognosis. DESIGN AND METHODS: Articles were
      obtained from MEDLINE (1966-present) using the keywords breast, cancer,
      carcinoma, and pregnancy. Additional articles were sought using the references of
      those obtained. A total of 171 articles were found, 125 in English. More than 100
      were reviewed, including 7 prospective and 40 retrospective studies, 6 case
      reports, and at least 47 review articles on various aspects of pregnancy and
      cancer. Data extraction was performed by 1 reviewer. RESULTS: Diagnostic delays
      are shorter than in the past but remain common. Mammography has a high false
      negative rate during pregnancy. Biopsy or needle aspiration are needed for
      diagnosis and cannot be postponed until after delivery. Pregnancy-associated
      cancers tend to occur at a later stage and be estrogen receptor-negative.
      However, they carry a similar prognosis to other breast cancers when matched for
      stage and age. Although modified radical mastectomy is the traditional treatment,
      breast-conserving therapy is increasingly common. Therapeutic radiation is
      contraindicated, but chemotherapy is relatively safe after the first trimester.
      Tamoxifen should be avoided in the first trimester and possibly beyond.
      CONCLUSIONS: Physicians should perform a thorough breast examination at the first
      prenatal visit and maintain a high index of suspicion for cancer. Patients who
      wish to continue their pregnancies have a growing array of treatment options.

PMID- 12511161
TI  - Hepatic resection for bilobar hepatocellular carcinoma: is it justified?
AB  - HYPOTHESIS: Patients with bilobar stage IVa hepatocellular carcinoma (HCC) are
      generally considered unsuitable for hepatic resection. Recent data suggest that
      palliative hepatic resection in selected patients with advanced HCC may result in
      a favorable survival outcome. The aim of the present study was to evaluate the
      operative outcome and survival benefits of hepatic resection for patients with
      bilobar HCC. DESIGN: Retrospective study. SETTING: Tertiary referral center.
      PATIENTS: The study comprised 78 patients who were diagnosed as having unilobar
      HCC and considered initially suitable candidates for curative hepatic resection
      on preoperative investigations from 1989 to 2000. Bilobar disease with discrete
      tumor nodules in the contralateral lobe was diagnosed in these patients on
      laparoscopy (44 patients) or laparotomy (34 patients) with the help of
      intraoperative ultrasonography. Fifteen patients (19%) underwent palliative
      hepatic resection (group A), and hepatic resection was not performed in the
      remaining 63 patients (81%) (group B). MAIN OUTCOME MEASURES: The
      clinicopathologic data and operative and survival outcomes of both groups of
      patients were compared. RESULTS: The clinicopathologic parameters were comparable
      in both groups of patients. In group A, 12 patients (80%) underwent major hepatic
      resection, and the mean +/- SEM size of the resected tumors was 8.3 +/- 0.9 cm.
      The operative morbidity and mortality were 20% and 0%, respectively. Treatment
      for tumors in the contralateral lobe included wedge excision (5 patients),
      alcohol injection (5 patients), cryotherapy (2 patients), and transarterial oily
      chemoembolization (3 patients). In group B, treatment for HCC included
      transarterial oily chemoembolization (42 patients), systemic chemotherapy (3
      patients), transarterial oily chemoembolization and systemic chemotherapy (5
      patients), cryotherapy (2 patients), tamoxifen (3 patients), and no treatment (8
      patients). The median survival of patients in group A was 19.5 months, with 4
      patients surviving for more than 3 years. The survival in group A was
      significantly better than in group B (median = 7.1 months; P =.008). On
      multivariate analysis, hepatic resection and preoperative serum alpha-fetoprotein
      level were the 2 independent factors that significantly affected patient
      survival. CONCLUSIONS: Hepatic resection for HCC in patients with stage IVa
      bilobar disease results in a better survival outcome than nonresectional
      therapies. It should be considered in selected patients with low operative risks
      and satisfactory liver function.

PMID- 12511162
TI  - Surgery in Panama.

PMID- 12511163
TI  - Image of the month. Perform surgical graduated dilatation of stenotic carotid
      artery.

PMID- 12511164
TI  - The clinical and economic correlates of nonspecific abdominal pain mismanaged by
      appendectomy.

PMID- 12511166
TI  - Zenker diverticulum.

PMID- 12511168
TI  - Positron emission tomography of regional brain metabolic responses to a
      serotonergic challenge and lethality of suicide attempts in major depression.
AB  - BACKGROUND: Lower serotonergic activity correlates with high-lethality suicide
      attempts in major depression. Postmortem studies of serotonin receptors in
      suicides localize changes to the ventral prefrontal cortex (PFC). We studied
      serotonergic response in ventral PFC in depressed patients surviving a high
      lethality suicide attempt. METHODS: Depressed patients with a history of a high
      lethality suicide attempt (n = 16) were compared with those with low-lethality
      attempts (n = 9) for level of depression, suicidal intent and ideation,
      impulsivity, aggression, and neuropsychological test performance. Subjects were
      scanned while medication free after a single-blind placebo and after fenfluramine
      hydrochloride administration on a second day. Brain responses were measured by
      positron emission tomography imaging of fludeoxyglucose F 18 and serial prolactin
      levels. Scans were compared by means of statistical parametric mapping.
      Correlations of changes in relative regional cerebral uptake (rCMRglu) with
      clinical and neuropsychological measures were assessed. RESULTS: Depressed high
      lethality suicide attempters had lower rCMRglu in ventral, medial, and lateral
      PFC compared with low-lethality attempters. This difference was more pronounced
      after fenfluramine administration. Lower ventromedial PFC activity was associated
      with lower lifetime impulsivity, higher suicidal intent (planning), and higher
      lethality suicide attempts. Higher verbal fluency was positively correlated with
      rCMRglu in the same regions. CONCLUSIONS: Prefrontal localized hypofunction and
      impaired serotonergic responsivity are proportional to the lethality of the
      suicide attempt and may mediate the effects of suicide intent and impulsivity on
      lethality. Positron emission tomographic neuroreceptor studies are needed to
      determine whether postmortem serotonin receptor findings are also present in vivo
      and contribute to the abnormal rCMRglu responses.

PMID- 12511169
TI  - Mineralocorticoid receptor function in major depression.
AB  - BACKGROUND: Negative feedback regulation of the hypothalamic-pituitary-adrenal
      axis occurs through a dual-receptor system of mineralocorticoid receptors (MR)
      and glucocorticoid receptors (GR). Their affinity for cortisol and their
      distribution in the brain differ. Studies using an MR antagonist have
      demonstrated that MR is active throughout the circadian rhythm. Because major
      depression is accompanied by increased glucocorticoid secretion and insensitivity
      to glucocorticoid feedback, and because glucocorticoids are capable of down
      regulating MR and GR, we expected that major depression would be accompanied by
      decreased MR activity. METHODS: To test this hypothesis, we administered
      spironolactone, an MR antagonist, to individuals with major depression and
      matched control subjects and assessed levels of corticotropin and cortisol
      secretion in response to this acute challenge. Studies were conducted in the
      morning, the time of peak activation of the hypothalamic-pituitary-adrenal axis.
      All patients were currently depressed and free of all medications. All controls
      were free of all psychiatric diagnoses and of all medications. RESULTS:
      Spironolactone treatment resulted in a significant increase in cortisol secretion
      levels in both groups. Depressed patients demonstrated higher cortisol secretion
      levels than control subjects. In addition, depressed patients demonstrated a
      different pattern of increase in cortisol secretion levels after spironolactone
      administration. Furthermore, a significant effect of spironolactone treatment on
      corticotropin secretion levels can be observed in depressed patients, whereas
      controls show no such effect. CONCLUSIONS: Despite high baseline cortisol levels,
      patients with major depression show high functional activity of the MR system.
      Paired with the body of evidence regarding decreased sensitivity to GR agonists,
      these data suggest an imbalance in the MR/GR ratio. The balance of MR and GR is
      known to affect brain serotonin systems and may play an etiologic role in
      serotonin receptor changes observed in patients with major depression.

PMID- 12511170
TI  - Depression and its influence on reproductive endocrine and menstrual cycle
      markers associated with perimenopause: the Harvard Study of Moods and Cycles.
AB  - BACKGROUND: Few studies have determined the impact of a lifetime history of major
      depression on an early transition to menopause. METHODS: Reproductive and
      psychiatric interviews and early follicular-phase blood specimens were obtained
      at study enrollment and every 6 months during 36 months of follow-up from 332
      women with and 644 women without a history of major depression, 36 to 45 years of
      age. We used menstrual cycle markers to determine inception of perimenopause,
      defined as time from study enrollment to a follow-up interview with: (1) 7-day or
      more change in menstrual cycle length; (2) a change in menstrual flow amount or
      duration; or (3) amenorrhea lasting at least 3 months. RESULTS: Women with a
      history of depression had 1.2 times the rate of perimenopause of women with no
      such history (95% confidence interval, 0.9-1.6). Compared with nondepressed
      women, depressed women with more pronounced depressive symptoms at study
      enrollment (Hamilton Rating Scale for Depression scores >8) had twice the risk of
      an earlier perimenopausal transition. Among the women with greater depressive
      symptoms (Hamilton scores >8), those who also reported use of antidepressants had
      nearly 3 times the risk of an earlier perimenopausal transition (hazard ratio,
      2.7; 95% confidence interval, 1.5-4.8) of nondepressed women. Women with a
      lifetime history of depression also had higher follicle-stimulating hormone and
      luteinizing hormone levels and lower estradiol levels at study enrollment and
      during the follow-up period after adjustment for covariates. CONCLUSION: A
      lifetime history of major depression may be associated with an early decline in
      ovarian function.

PMID- 12511171
TI  - Using chronic pain to predict depressive morbidity in the general population.
AB  - BACKGROUND: Pain syndrome is thought to play a role in depression. This study
      assesses the prevalence of chronic (>or= 6 months' duration) painful physical
      conditions (CPPCs) (joint/articular, limb, or back pain, headaches, or
      gastrointestinal diseases) and their relationship with major depressive disorder.
      METHODS: We conducted a cross-sectional telephone survey of a random sample of 18
      980 subjects from 15 to 100 years old representative of the general populations
      of the United Kingdom, Germany, Italy, Portugal, and Spain. Answers provided
      during telephone interviews using the Sleep-EVAL system were the main outcome
      measure. Interviews included questions about mental disorders and medical
      conditions. Data on painful physical conditions were obtained through questions
      about medical treatment, consultations, and/or hospitalizations for medical
      conditions and a list of 42 diseases. RESULTS: Of all subjects interviewed, 17.1%
      reported having at least 1 CPPC (95% confidence interval [CI], 16.5%-17.6%). At
      least 1 depressive symptom (sadness, depression, hopelessness, loss of interest,
      or lack of pleasure) was present in 16.5% of subjects (95% CI, 16.0%-17.1%);
      27.6% of these subjects had at least 1 CPPC. Major depressive disorder was
      diagnosed in 4.0% of subjects; 43.4% of these subjects had at least 1 CPPC, which
      was 4 times more often than in subjects without major depressive disorder (odds
      ratio [OR], 4.0; 95% CI, 3.5-4.7). In a logistic regression model, CPPC was
      strongly associated with major depressive disorder (OR: CPPC alone, 3.6; CPPC +
      nonpainful medical condition, 5.2); 24-hour presence of pain made an independent
      contribution to major depressive disorder diagnosis (OR, 1.6). CONCLUSIONS: The
      presence of CPPCs increases the duration of depressive mood. Patients seeking
      consultation for a CPPC should be systematically evaluated for depression.

PMID- 12511172
TI  - Transcranial magnetic stimulation of left temporoparietal cortex and medication
      resistant auditory hallucinations.
AB  - BACKGROUND: Neuroimaging studies suggest that auditory hallucinations (AHs) of
      speech arise, at least in part, from activation of brain areas underlying speech
      perception. One-hertz repetitive transcranial magnetic stimulation (rTMS)
      produces sustained reductions in cortical activation. Recent results of 4-day
      administration of 1-Hz rTMS to left temporoparietal cortex were superior to those
      of sham stimulation in reducing AHs. We sought to determine if a more extended
      trial of rTMS could significantly reduce AHs that were resistant to antipsychotic
      medication. METHODS: Twenty-four patients with schizophrenia or schizoaffective
      disorder and medication-resistant AHs were randomly allocated to receive rTMS or
      sham stimulation for 9 days at 90% of motor threshold. Patients receiving sham
      stimulation were subsequently offered an open-label trial of rTMS.
      Neuropsychological assessments were administered at baseline and during and
      following each arm of the trial. RESULTS: Auditory hallucinations were robustly
      improved with rTMS relative to sham stimulation. Frequency and attentional
      salience were the 2 aspects of hallucinatory experience that showed greatest
      improvement. Duration of putative treatment effects ranged widely, with 52% of
      patients maintaining improvement for at least 15 weeks. Repetitive transcranial
      magnetic stimulation was well tolerated, without evidence of neuropsychological
      impairment. CONCLUSIONS: These data suggest that the mechanism of AHs involves
      activation of the left temporoparietal cortex. One-hertz rTMS deserves additional
      study as a possible treatment for this syndrome.

PMID- 12511173
TI  - A specific deficit in context processing in the unaffected siblings of patients
      with schizophrenia.
AB  - BACKGROUND: Understanding the biological basis of complex, heritable illnesses
      such as schizophrenia is facilitated by sensitive and functionally specific
      measures of intermediate processes. Context processing is a theoretically
      motivated construct associated with executive function. Impairments in this
      process have been associated with dysfunction of the prefrontal cortex. In the
      present study, we evaluated whether a specific deficit in context processing
      could be associated with the unexpressed genetic liability to schizophrenia.
      METHODS: Twenty-four patients with schizophrenia, 24 unaffected siblings and 36
      control subjects completed a version of the AX task with (1) a condition that
      required context processing and (2) an expectancy condition in which intact
      context processing could lead to errors. RESULTS: Patients and unaffected
      siblings performed relatively worse in the context processing condition, whereas
      controls performed relatively worse in the expectancy condition. A double
      dissociation between siblings and controls (F = 9.5, P<.005) constituted strong
      evidence of a specific deficit in context processing associated with a familial
      or genetic liability to schizophrenia. Preliminary evidence of high diagnostic
      efficiency was also noted (specificity, 38%; and sensitivity, 100%). CONCLUSIONS:
      Context processing deficits have been associated with dorsolateral prefrontal
      cortex dysfunctions in schizophrenia. Such a dysfunction may occur even when
      genetic liability to schizophrenia is unexpressed clinically. The present method
      of demonstrating a double dissociation may be a useful approach to exploring
      endophenotypes related to specific cognitive and neural processes that can be
      measured in ways sensitive to subtle group differences.

PMID- 12511174
TI  - Regional specificity in the neuropathologic substrates of schizophrenia: a
      morphometric analysis of Broca's area 44 and area 9.
AB  - BACKGROUND: Numerous recent studies of postmortem schizophrenic brains have
      reported the presence of structural abnormalities in the dorsolateral prefrontal
      cortex (dlPFC) that are consistent with a reduction of neuropil. Ventrolateral
      prefrontal areas have been studied less extensively, and therefore it is not
      clear whether these cortices exhibit pathologic abnormalities of the same type
      and magnitude. Because thought disturbances in schizophrenic patients involve
      language processing, we have performed a morphometric analysis of Broca's area in
      the ventral frontal lobe. METHODS: Neuronal and glial density and somal size were
      assessed via stereologic cell counting in postmortem samples of Broca's area 44
      in 9 schizophrenic patients and 14 normal controls. Cell density was reexamined
      in dorsolateral prefrontal area 9 as an internal control. RESULTS: We did not
      detect abnormalities in overall or laminar neuronal density, glial density,
      cortical thickness, or somal size in area 44 of schizophrenic patients. In
      contrast, neuronal density in area 9 exhibited a 12% increase in the
      schizophrenic cohort, replicating previous findings. In addition, there was a
      significant effect of disease on laminar neuronal density in area 9, with
      neuronal density tending to be higher (7%-29%) in all layers. CONCLUSIONS: The
      absence of significant cytoarchitectonic abnormalities in Broca's area in the
      same brains in which the dlPFC exhibited an increase in neuronal density suggests
      that the neuropil deficit is a regionally specific pathologic finding in
      schizophrenia and indicates that the dlPFC is a particularly vulnerable target of
      the disease process.

PMID- 12511176
TI  - Comparing and combining naltrexone and acamprosate in relapse prevention of
      alcoholism: a double-blind, placebo-controlled study.
AB  - BACKGROUND: Naltrexone and acamprosate have been shown to be effective in relapse
      prevention of alcoholism via different pharmacologic mechanisms. Since it remains
      uncertain whether both substances are equally efficient and whether a combination
      of both drugs potentiates the efficacy, we conducted the first published
      controlled study comparing and combining both compounds. METHODS: After
      detoxification, 160 patients with alcoholism participated in a randomized, double
      blind, placebo-controlled protocol. Patients received naltrexone, acamprosate,
      naltrexone plus acamprosate, or placebo for 12 weeks. Patients were assessed
      weekly by interview, self-report, questionnaires, and laboratory screening. Time
      to first drink, time to relapse, and the cumulative abstinence time were the
      primary outcome measures. RESULTS: Naltrexone, acamprosate, and the combined
      medication were significantly more effective than placebo. Comparing the course
      of nonrelapse rates between naltrexone and acamprosate, the naltrexone group
      showed a tendency for a better outcome regarding time to first drink and time to
      relapse. The combined medication was most effective with significantly lower
      relapse rates than placebo and acamprosate but not naltrexone. CONCLUSIONS: The
      results of this study support the efficacy of pharmacotherapeutic strategies in
      the relapse prevention of alcoholism. Naltrexone and acamprosate, especially in
      combination, considerably enhance the potential of relapse prevention.

PMID- 12511175
TI  - Clozapine treatment for suicidality in schizophrenia: International Suicide
      Prevention Trial (InterSePT).
AB  - BACKGROUND: Approximately 50% of patients with schizophrenia or schizoaffective
      disorder attempt suicide, and approximately 10% die of suicide. Study results
      suggest that clozapine therapy significantly reduces suicidal behavior in these
      patients. METHODS: A multicenter, randomized, international, 2-year study
      comparing the risk for suicidal behavior in patients treated with clozapine vs
      olanzapine was conducted in 980 patients with schizophrenia or schizoaffective
      disorder, 26.8% of whom were refractory to previous treatment, who were
      considered at high risk for suicide because of previous suicide attempts or
      current suicidal ideation. To equalize clinical contact across treatments, all
      patients were seen weekly for 6 months and then biweekly for 18 months.
      Subsequent to randomization, unmasked clinicians at each site could make any
      interventions necessary to prevent the occurrence of suicide attempts. Suicidal
      behavior was assessed at each visit. Primary end points included suicide attempts
      (including those that led to death), hospitalizations to prevent suicide, and a
      rating of "much worsening of suicidality" from baseline. Masked raters, including
      an independent suicide monitoring board, determined when end point criteria were
      achieved. RESULTS: Suicidal behavior was significantly less in patients treated
      with clozapine vs olanzapine (hazard ratio, 0.76; 95% confidence interval, 0.58
      0.97; P =.03). Fewer clozapine-treated patients attempted suicide (34 vs 55; P
      =.03), required hospitalizations (82 vs 107; P =.05) or rescue interventions (118
      vs 155; P =.01) to prevent suicide, or required concomitant treatment with
      antidepressants (221 vs 258; P =.01) or anxiolytics or soporifics (301 vs 331; P
      =.03). Overall, few of these high-risk patients died of suicide during the study
      (5 clozapine vs 3 olanzapine-treated patients; P =.73). CONCLUSIONS: Clozapine
      therapy demonstrated superiority to olanzapine therapy in preventing suicide
      attempts in patients with schizophrenia and schizoaffective disorder at high risk
      for suicide. Use of clozapine in this population should lead to a significant
      reduction in suicidal behavior.

PMID- 12511177
TI  - Malignant melanoma: effects of a brief, structured psychiatric intervention on
      survival and recurrence at 10-year follow-up.
AB  - BACKGROUND: The influence of psychiatric intervention on cancer outcome remains a
      topic of considerable debate. We previously reported the survival benefits for 68
      patients with malignant melanoma 5 to 6 years following their participation in a
      structured psychiatric group intervention. In this article, we report the effects
      of the intervention on disease outcome in these same patients at the 10-year
      follow-up. METHODS: In this univariate analysis, the survival and recurrence
      distributions for the intervention and control groups were estimated using the
      Kaplan-Meier method, and were tested for equality by the log-rank test. The
      multivariate analysis used the Cox proportional hazards regression model with the
      following prognostic factors: age, sex, Breslow depth, tumor site, and treatment
      status (ie, intervention group vs control group). RESULTS: When analyzed as
      single covariates, differences between the intervention and control groups were
      not significant for outcome at the 10-year follow-up. However, being male and
      having a greater Breslow depth were predictive of poorer outcome. Analysis of
      multiple covariates also revealed that sex and Breslow depth were significant for
      recurrence and survival. In addition, participation in the intervention was
      significant for survival. After adjusting for sex and Breslow depth,
      participation in the intervention remained significant for survival. CONCLUSIONS:
      These findings suggest that the survival benefit of the intervention has weakened
      since the 5- to 6-year follow-up; however, it has not entirely disappeared. At
      the 10-year follow-up, participation in the intervention remained predictive of
      survival when statistically controlling for the effects of other known prognostic
      indicators. Despite the potential health benefits, we do not propose that
      psychiatric intervention be used in lieu of standard medical care, but as one of
      its integral components.

PMID- 12511178
TI  - Fluoride plus aluminum: useful tools in laboratory investigations, but messengers
      of false information.
AB  - Aluminofluoride complexes (AlF(x)) form spontaneously in aqueous solutions
      containing fluoride and traces of aluminum ions and appear to act as phosphate
      analogs. These complexes have become widely utilized in laboratory investigations
      of various guanine nucleotide-binding proteins. Reflecting on many laboratory
      studies, a new mechanism of fluoride and aluminum action on the cellular level is
      being suggested. The long-term synergistic effects of these ions in living
      environment and their hidden danger for human health are not yet fully
      recognized.

PMID- 12511179
TI  - Short-term NO synthase inhibition and the ATP affinity of cardiac Na,K-ATPase.
AB  - It was previously shown that 4 hours lasting inhibition of nitric oxide synthesis
      by administration of an L-arginine analogue, the A(G)-nitro-L-arginine methyl
      ester (L-NAME) changed the affinity of the Na-binding site of Na,K-ATPase thus
      resulting in elevation of enzyme activity especially at higher concentrations of
      sodium. Using the same experimental model, we focused our attention in the
      present study to the question of binding of ATP to the enzyme molecule in the
      left ventricle (LV), ventricular septum (S) and the right ventricle (RV) of the
      dog heart. Activation of the enzyme by increasing concentrations of ATP revealed
      a significant increase of the Vmax only in septum (by 38 %). The K(M) increased
      significantly in septum (by 40 %) and in left ventricle (by 56 %) indicating an
      altered sensitivity of the ATP-binding site of Na,K-ATPase in the hearts of NO
      deficient animals. The alterations of Na,K-ATPase in its ability to bind and
      hydrolyze ATP are localized to the tissue surrounding the cavity of the left
      ventricle.

PMID- 12511180
TI  - Role of nNOS in regulation of renal function in hypertensive Ren-2 transgenic
      rats.
AB  - The present study was performed to evaluate the role of neuronal nitric oxide
      synthase (nNOS)-derived nitric oxide (NO) during the developmental phase of
      hypertension in transgenic rats harboring the mouse Ren-2 renin gene (TGR). The
      first aim of the present study was to examine nNOS mRNA expression in the renal
      cortex and to assess the renal functional responses to intrarenal nNOS inhibition
      by S-methyl-L-thiocitrulline (L-SMTC) in heterozygous TGR and in age-matched
      transgene-negative Hannover Sprague-Dawley rats (HanSD). The second aim was to
      evaluate the role of the renal sympathetic nerves in mediating the renal
      functional responses to intrarenal nNOS inhibition. Thus, we also evaluated the
      effects of intrarenal L-SMTC administration in acutely denervated TGR and HanSD.
      Expression of nNOS mRNA in the renal cortex was significantly increased in TGR
      compared with HanSD. Intrarenal administration of L-SMTC decreased the glomerular
      filtration rate (GFR), renal plasma flow (RPF) and sodium excretion and increased
      renal vascular resistance (RVR) in HanSD. In contrast, intrarenal inhibition of
      nNOS by L-SMTC did not alter GFR, RPF or RVR and elicited a marked increase in
      sodium excretion in TGR. This effect of intrarenal L-SMTC was not observed in
      acutely denervated TGR. These results suggest that during the developmental phase
      of hypertension TGR exhibit an impaired renal vascular responsiveness to nNOS
      derived NO or an impaired ability to release NO by nNOS despite enhanced
      expression of nNOS mRNA in the renal cortex. In addition, the data indicate that
      nNOS-derived NO increases tubular sodium reabsorption in TGR and that the renal
      nerves play an important modulatory role in this process.

PMID- 12511181
TI  - Effect of different cycling frequencies during incremental exercise on the venous
      plasma potassium concentration in humans.
AB  - The effect of different muscle shortening velocity was studied during cycling at
      a pedalling rate of 60 and 120 rev.min(-1) on the [K+]v in humans. Twenty-one
      healthy young men aged 22.5+/-2.2 years, body mass 72.7+/-6.4 kg, VO2 max 3.720+/
      0.426 l. min(-1), performed an incremental exercise test until exhaustion. The
      power output increased by 30 W every 3 min, using an electrically controlled
      ergometer Ergoline 800 S (see Zoladz et al. J. Physiol. 488: 211-217, 1995). The
      test was performed twice: once at a cycling frequency of 60 rev.min(-1) (test A)
      and a few days later at a frequency of 120 rev. min(-1) (test B). At rest and at
      the end of each step (i.e. the last 15 s) antecubital venous blood samples for
      [K+]p were taken. Gas exchange variables were measured continuously (breath-by
      breath) using Oxycon Champion Jaeger. The pre-exercise [K+]v in both tests was
      not significantly different amounting to 4.24+/-0.36 mmol.l(-1) in test A, and
      4.37+/-0.45 mmol.l(-1) in test B. However, the [K+]p during cycling at 120 rev.
      min(-1) was significantly higher (p<0.001, ANOVA for repeated measurements) at
      each power output when compared to cycling at 60 rev.min(-1). The maximal power
      output reached 293+/-31 W in test A which was significantly higher (p<0.001) than
      in test B, which amounted to 223+/-40 W. The VO2max values in both tests reached
      3.720+/-0.426 l. min(-1) vs 3.777+/-0.514 l. min(-1). These values were not
      significantly different. When the [K+]v was measured during incremental cycling
      exercise, a linear increase in [K+]v was observed in both tests. However, a
      significant (p<0.05) upward shift in the [K+]v and a % VO2max relationship was
      detected during cycling at 120 rev.min(-1). The [K+]v measured at the VO2max
      level in tests A and B amounted to 6.00+/-0.47 mmol.l-1 vs 6.04+/-0.41 mmol.l-1,
      respectively. This difference was not significant. It may thus be concluded that:
      a) generation of the same external mechanical power output during cycling at a
      pedalling rate of 120 rev.min(-1) causes significantly higher [K+]v changes than
      when cycling at 60 rev.min(-1), b) the increase of venous plasma potassium
      concentration during dynamic incremental exercise is linearly related to the
      metabolic cost of work expressed by the percentage of VO2max (increase as
      reported previously by Vollestad et al. J. Physiol. 475: 359-368, 1994), c) there
      is a tendency towards upward up shift in the [K+]v and % VO2max relation during
      cycling at 120 rev.min(-1) when compared to cycling at 60 rev.min(-1).

PMID- 12511182
TI  - Insulin-like growth factor binding protein-3 in patients with liver cirrhosis.
AB  - Aim of the study was to evaluate serum levels of insulin-like growth factor
      binding protein-3 in patients with liver cirrhosis and to compare serum IGFBP-3
      levels with other liver function tests. Fifty-one patients with liver cirrhosis
      were selected for our study. We measured IGFBP-3 (1.67+/-1.06 mg/l, mean+/-SD),
      albumin (32+/-8 g/l), prealbumin (0.22+/-0.14 g/l), AST (2.29+/-2.38 microkat/l),
      ALT (2.11+/-4.83 microkat/l) and cholinesterase (mean 78.6+/-45.2 microkat/l) in
      the serum. There was a significant positive correlation of serum IGFBP-3 with
      serum albumin and serum cholinesterase. The correlation coefficient was much
      lower between serum IGFBP-3 and serum prealbumin. There was no significant
      correlation between serum AST, ALT and IGFBP-3. Serum IGFBP-3 proves to be a
      better marker for the hepatic synthetic capacity than serum albumin or
      cholinesterase.

PMID- 12511183
TI  - Hyperinsulinemia and oxidative stress.
AB  - The aim of the study was to compare the effect of short-term hyperglycemia and
      short-term hyperinsulinemia on parameters of oxidative stress in Wistar rats.
      Twenty male rats (aged 3 months, average weight 325 g) were tested by
      hyperinsulinemic clamp (100 IU/l) at two different glycemia levels (6 and 12
      mmol/l). Further 20 rats were used as a control group infused with normal saline
      (instead of insulin) and 30 % glucose simultaneously. Measured parameters of
      oxidative stress were malondialdehyd (MDA), reduced glutathion (GSH) and total
      antioxidant capacity (AOC). AOC remained unchanged during hyperglycemia and
      hyperinsulinemia. Malondialdehyde (as a marker of lipid peroxidation) decreased
      significantly (p<0.05) during the euglycemic hyperinsulinemic clamp, and
      increased significantly during isolated hyperglycemia without hyperinsulinemia.
      Reduced glutathion decreased significantly (p<0.05) during hyperglycemia without
      hyperinsulinemia. These results suggest that the short-term exogenous
      hyperinsulinemia reduced the production of reactive oxygen species (ROS) during
      hyperglycemia in an animal model compared with the control group.

PMID- 12511184
TI  - Advanced glycation end-products and advanced oxidation protein products in
      patients with diabetes mellitus.
AB  - Accelerated glycoxidation takes part in the development of diabetic
      complications. We determined advanced glycation end-products (AGEs) and advanced
      oxidation protein products (AOPP) in the sera of 52 patients with diabetes
      mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their
      relationship to the compensation of the disease. AGEs were estimated
      spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro
      photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11+/-1.15 x
      10(3) AU/g vs controls 4.08+/-0.71 x 10(3) AU/g, p<0.001, vs DM1 4.14+/-0.86 x
      10(3) AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated
      significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50+/
      75.15 micromol/l vs healthy subjects 79.80+/-23.72 micromol/l, p<0.001, vs DM1
      97.50+/-30.91 micromol/l, p<0.005, DM1 vs controls p<0.05). There was a tight
      correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47
      (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1
      only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight
      but not significant differences in AGEs and AOPP levels were observed in patients
      with or without diabetic complications. Oxidative stress is increased in both
      types of DM, more in Type 2 where it contributes to the formation of
      glycoxidation products.

PMID- 12511185
TI  - Does magnesium dysbalance participate in the development of insulin resistance in
      early stages of renal disease?
AB  - We investigated the potential role of magnesium (Mg) dysbalance in the
      pathogenesis of insulin resistance (IR) in patients with mildly-to-moderately
      decreased renal function (creatinine: 142.8+/-11.0 mmol/l). The data were
      compared to those of 8 age- and sex-matched healthy controls (CTRL). The standard
      oral glucose tolerance test (oGTT) was performed in 61 patients. Twenty-two
      patients were classified as IR according to their values on fasting and after
      load immunoreactive insulin concentrations. Serum and total erythrocyte Mg
      (tErMg) (atomic absorption spectro-photometry) and free erythrocyte Mg (fErMg)
      concentrations ((31) P NMR spectroscopy) were determined prior to and two hours
      after the glucose load. Ten out of 39 insulin-sensitive (IS) patients, but only
      one out of 22 insulin-resistant (IR) patients, had a low basal fErMg
      concentration (<162.2 micromol/l, chi2, p<0.01). IR patients had higher serum Mg,
      total erythrocyte Mg and bound erythrocyte Mg (bErMg) concentrations (both before
      and after glucose load) when compared with the IS group. Both groups responded to
      the glucose load with a significant decrease in serum Mg concentration (within
      the normal range), while the IR group also exhibited a decline in tErMg and
      bErMg. The mean sum of insulin needed to metabolize the same glucose load
      correlated positively with tErMg (r=0.545, p<0.01) and bErMg (r=0.560, p<0.01) in
      the IR patients. It is concluded that, at an early stage of renal dysfunction, IR
      is not associated with the decline in free erythrocyte Mg concentration, but the
      magnesium handling in red blood cells is altered.

PMID- 12511186
TI  - Detection of antiendothelial cell antibodies in patients with connective tissue
      diseases by flow cytometry and their relation to endothelial cell activation.
AB  - Antiendothelial cell antibodies (AECA) have been detected by flow cytometry
      analysis in 23 out of 80 patients with connective tissue diseases. Ten out of 19
      serum samples from patients with systemic lupus erythematosus (SLE) were
      positive. These antibodies were not detectable in healthy donors. We examined the
      capacity of serum samples to induce endothelial cell activation by modulating
      cell adhesion molecule expression on human umbilical vein endothelial cells. We
      found that sera from both AECA-positive and AECA-negative patient groups induced
      a significantly higher expression of E-selectin compared to healthy controls
      (P<0.05). There were no differences in the ICAM-1 on VCAM-1 expression. Our data
      suggest that increased E-selectin expression in activated endothelium in patients
      with various connective tissue disorders is not related to the production of
      AECA.

PMID- 12511187
TI  - Biliary decompression reduces the susceptibility to ethanol-induced ulcer in
      jaundiced rats.
AB  - We investigated the gastric response to an ulcerogenic irritant and the change in
      gastric functions in an experimental rat model of obstructive jaundice, with or
      without biliary drainage. After biliary obstruction for 14 days, rats with
      ligated bile duct (BDL) were randomly divided into three groups: BDL group
      without biliary drainage, BDL followed by choledochoduodenostomy (CD) or a
      choledochovesical fistula (CVF). The gastric functions were evaluated 2 weeks
      after the surgery. Gastric damage, induced by orogastric administration of
      ethanol, was evaluated 30 min later using a lesion index and microscopic scoring
      was then performed on fixed stomachs. Basal gastric acid secretion was measured
      by the pyloric ligation method. The lesion index and maximum lesion depth did not
      differ in the BDL and sham groups, while they were significantly reduced in the
      CD group. Gastric acid output and secretory volume were reduced in the BDL group
      compared to the sham group, while these reductions were abolished in the CD
      group. Afferent denervation with capsaicin further reduced the ulcer index in the
      later group. Our data suggest that gastric mucosal susceptibility to injury is
      dependent on the normal flow of bile into the duodenal lumen, which appears to be
      a requirement for adaptive gastric cytoprotection.

PMID- 12511188
TI  - Hematopoiesis-stimulating and anti-tumor effects of repeated administration of
      diclofenac in mice with transplanted fibrosarcoma cells.
AB  - Positive effects of repeated administration of diclofenac, an inhibitor of
      prostaglandin synthesis, in terms of prevention of tumor development and
      stimulation of hematopoiesis have been observed in C3H mice transplanted
      subcutaneously with G:5:113 fibrosarcoma cells. Fourteen-day treatment with
      diclofenac (3.75 microg/kg/day) started from day 5 after tumor cell
      transplantation. Measurements of tumors and hematological examinations were
      performed on day 30. The results strongly suggest the possibility that inhibitors
      of prostaglandin synthesis (non-steroidal anti-inflammatory drugs) may be used in
      oncological practice where the observed effects are highly desirable.

PMID- 12511189
TI  - Variability of mammary carcinogenesis induction in female Sprague-Dawley and
      Wistar:Han rats: the effect of season and age.
AB  - It is important to determine and clarify the variability of mammary
      carcinogenesis induction in animal experimental studies particularly in
      connection with chemoprevention projects. The circannual seasonal rhythms of
      hormone levels or various parameters within the immune system may involve factors
      participating in mammary gland carcinogenesis. In our study, 19 experiments were
      conducted and all of them lasted for about 25 weeks after chemical carcinogen
      administration (DMBA or NMU) under standard laboratory conditions. Females of two
      rat strains - a medium susceptible Sprague-Dawley strain and a very low
      susceptible Wistar:Han were used. We observed not only the effect of seasonal
      changes but also the effect of age after single or repeated carcinogen
      administration. The seasonal dependence of mammary carcinogenesis with higher
      tumor incidence during long days in comparison with winter short days has been
      demonstrated in Sprague-Dawley rats. In experiments on the Wistar:Han strain,
      certain features of seasonal character were recorded, although the very low
      susceptibility of this strain to mammary carcinogenesis might have influenced the
      results. A limited period of carcinogen administration in early puberty around
      postnatal days 43-46 (higher susceptibility), when compared to the period after
      postnatal day 50, is the factor significantly increasing incidence and frequency
      of mammary carcinogenesis in the Sprague-Dawley strain. Our results indicate the
      need to consider the effect of season and age of animals at the time of
      carcinogen administration on rat mammary carcinogenesis induction. However, the
      application of the results obtained in one strain of experimental animals may
      only lead to misleading conclusions.

PMID- 12511190
TI  - Modulation of the phototoxic effect of hypericin in human leukemia CEM cell line
      by N-ethylmaleimide, amiloride and omeprazole.
AB  - Hypericin is a photosensitizing plant pigment from Hypericum perforatum with
      multiple modes of light-induced biological activities due to production of
      singlet oxygen and/or excited-state proton transfer with consequent pH drop in
      the hypericin environment. In the present work, we studied the effects of three
      inhibitors of crucial mechanisms responsible for intracellular pH (pHi)
      regulation on hypericin phototoxicity: N-ethylmaleimide (NEM), an inhibitor of H+
      ATPase, 5'-(N,N-dimethyl)-amiloride (DMA), an inhibitor of Na+/H+ exchanger, and
      omeprazole (OME), an inhibitor of H+K+-ATPase. Our experiments show that the
      effect of hypericin at 1 x 10(-5) and 1 x 10(-6) mol x l(-1) was significantly
      potentiated by NEM (1 x 10(-7)-1 x 10(--9) mol x l(-1)) and DMA (1 x 10(-6) and 1
      x 10(-7) mol x l(-1)) in leukemic CEM cell line. On the other hand, OME had no
      significant effect on hypericin cytotoxicity. Our results support the hypothesis
      that the excited-state proton transfer and the consequent acidification of
      hypericin environment could play a role in the biological activity of hypericin.

PMID- 12511191
TI  - The New Scientist and primate research: the strange case of Dr Jekyll and Mr
      Hyde?

PMID- 12511192
TI  - Reduction, refinement and replacement: putting the immune system to work.
AB  - Many chemicals are known to be, or have been implicated as, contact allergens,
      and allergic contact dermatitis is an important occupational and environmental
      health issue. It is the responsibility of toxicologists to identify those
      chemicals that have the potential to induce skin sensitisation, and to assess the
      conditions under which there will exist a risk to human health. This article
      describes progress that has been made in the development of new approaches to the
      toxicological evaluation of skin sensitisation, and the benefits to animal
      welfare that such developments have already produced, and are likely to produce
      in the future. In this context, the local lymph node assay is described with
      regard to hazard identification and risk assessment, and possible strategies for
      the development of in vitro approaches to safety assessment are discussed.

PMID- 12511193
TI  - Comments on the report of the House of Lords Select Committee on Animals in
      Scientific Procedures.
AB  - This commentary comprises our responses to each of the seven conclusions and
      twenty-four recommendations made in the report of the House of Lords Select
      Committee on Animals in Scientific Procedures, published in July 2002.

PMID- 12511194
TI  - Mutations of penicillin acylase residue B71 extend substrate specificity by
      decreasing steric constraints for substrate binding.
AB  - Two mutant forms of penicillin acylase from Escherichia coli strains, selected
      using directed evolution for the ability to use glutaryl-L-leucine for growth
      [Forney, Wong and Ferber (1989) Appl. Environ. Microbiol. 55, 2550-2555], are
      changed within one codon, replacing the B-chain residue Phe(B71) with either Cys
      or Leu. Increases of up to a factor of ten in k (cat)/ K (m) values for
      substrates possessing a phenylacetyl leaving group are consistent with a decrease
      in K (s). Values of k (cat)/ K (m) for glutaryl-L-leucine are increased at least
      100-fold. A decrease in k (cat)/ K (m) for the Cys(B71) mutant with increased pH
      is consistent with binding of the uncharged glutaryl group. The mutant proteins
      are more resistant to urea denaturation monitored by protein fluorescence, to
      inactivation in the presence of substrate either in the presence of urea or at
      high pH, and to heat inactivation. The crystal structure of the Leu(B71) mutant
      protein, solved to 2 A resolution, shows a flip of the side chain of Phe(B256)
      into the periphery of the catalytic centre, associated with loss of the pi
      stacking interactions between Phe(B256) and Phe(B71). Molecular modelling
      demonstrates that glutaryl-L-leucine may bind with the uncharged glutaryl group
      in the S(1) subsite of either the wild-type or the Leu(B71) mutant but with
      greater potential freedom of rotation of the substrate leucine moiety in the
      complex with the mutant protein. This implies a smaller decrease in the
      conformational entropy of the substrate on binding to the mutant proteins and
      consequently greater catalytic activity.

PMID- 12511195
TI  - Help-seeking behaviors of blacks and whites dying from coronary heart disease.
AB  - OBJECTIVES: This study sought to determine whether blacks and whites with life
      threatening cardiac events differ in likelihood of help seeking, types of help
      sought, or likelihood of reaching the hospital before death. DESIGN: Death
      certificates were used to identify all coronary heart disease-related deaths
      occurring in 1988-89 among 45- to 74-year-old, black and white, non
      institutionalized residents of three contiguous inner-city districts in Boston,
      Massachusetts, USA. An informant was interviewed about the decedent's health
      status, access to care and pre-mortal help-seeking behaviors. RESULTS: Among the
      232 decedents analyzed, there were no racial differences in the likelihood of
      help seeking. Among those who sought help, there were no racial differences in
      the likelihood of reaching the hospital. However, blacks were more likely than
      whites to engage in two specific help-seeking behaviors: calling the 911
      emergency system, and trying to reach an emergency room. CONCLUSION: In an area
      where blacks and whites were similar with respect to socioeconomic status and
      access to care, race did not affect the likelihood of help seeking or the
      likelihood of succeeding in reaching the hospital before death.

PMID- 12511196
TI  - Organ donation and transplantation: ethnic differences in knowledge and opinions
      among urban high school students.
AB  - PURPOSE: To assess knowledge and opinions about the process of human organ
      donation and transplantation among American teenagers. METHODS: A culturally
      sensitive 35-item self-administered survey assessing knowledge, opinions, and
      family discussion about organ donation and transplantation was conducted with 247
      students in 13 separate classrooms encompassing three urban high schools in the
      same city. RESULTS: More than 50% of the students did not know the correct
      answers to 13 of the 16 questions on factual knowledge. The sources of
      information about organ donation and transplantation among students were
      primarily television and school. African-Americans and Asian-Americans were
      significantly less likely to want to become organ donors when compared to non
      African-Americans and non-Asian-Americans, respectively. Asian-Americans were
      significantly less likely to have discussed the matter with family members.
      CONCLUSIONS: Accurate, up-to-date, culturally sensitive youth-oriented health
      education that emphasizes family discussions about organ donation and
      transplantation is needed.

PMID- 12511197
TI  - Rural and urban South African women's awareness of cancers of the breast and
      cervix.
AB  - OBJECTIVE: The investigation sought to establish the awareness of breast and
      cervical cancers among women of African descent, in both rural and urban areas,
      especially considering the oppression and deprivation experienced by this group.
      DESIGN: Two groups of randomly selected women in a rural (n = 70) and urban (n =
      70) area were interviewed using a structured questionnaire assessing their
      knowledge and attitudes regarding breast and cervical cancer and screening
      options. RESULTS: The age range of the sample was 21-59 years with a mean of
      35.23 years. Almost one-fifth of the women had not heard of these cancers, and
      almost half were unaware of the breast self-examination technique. Over one-third
      did not know about tests for breast cancer and more than half were unaware of
      tests for cervical cancer. Generally lower awareness levels were found in older
      and rural women who were also significantly more inclined to consult traditional
      healers (than doctors) about lumps in their breast or abnormal cervical bleeding.
      CONCLUSION: The findings are of great concern and represent a significant
      challenge in post-apartheid South Africa. The need for vigorous health promotion
      programmes cannot be sufficiently emphasised, especially in view of the benefits
      of early detection and treatment. There also needs to be particular focus on
      rural women, considering the inadequate health care resources in their
      communities and the socio-economic hardships facing them. Women in these
      communities must be empowered with knowledge about their health and illness
      prevention options.

PMID- 12511198
TI  - Knowledge of stroke risk, signs of stroke, and the need for stroke education
      among children with sickle cell disease and their caregivers.
AB  - OBJECTIVES: This study assessed stroke knowledge and the need for stroke
      education among children with sickle cell disease (SCD) and their caregivers.
      METHODS: A cross-sectional study was conducted and includes: (1) structured
      interviews of 44 children with SCD and their 50 caregivers, and (2) a self
      administered survey completed by medical directors of 22 SCD centers. The
      participants were interviewed regarding stroke knowledge and stroke educational
      materials. RESULTS: Among the caregivers, only 34% named stroke as a complication
      associated with SCD, 36% were aware that their children were at higher risk, and
      46% were not able to identify any warning signs of stroke. Only 11% of the
      children could accurately describe a stroke. Although 82% of the medical
      directors provided stroke information to caregivers, only 50% provided stroke
      educational materials to children. Caregivers and children were interested in
      receiving information about stroke. The preferred format for the educational
      material was a pamphlet for adults and a video for the children. CONCLUSIONS:
      Children with SCD, caregivers, and healthcare providers need and desire
      educational materials about stroke. Educational materials to improve knowledge
      about stroke may be an important strategy to increase completion of stroke
      screening tests.

PMID- 12511199
TI  - Controlled delivery system for norethindrone based on biodegradable poly
      alpha,beta-(hydroxyalkyl)-DL-aspartamide.
AB  - The article describes the preparation of poly-(hydroxyalkyl)-DL-aspartamide
      (PHAA) by a (ring) opening reaction by hydroxyalkylamino; norethindrone (NET), as
      a model drug, was coupled to the polymers via hydroxyalkylamino spacers. PHAA and
      NETPHAA conjugates were characterized by FTIR, DSC, x-ray,(13)C NMR, and scanning
      electron microscopy and their structure were confirmed. The biocompatibility of
      PHAA was tested. The study showed that PHAA was a hydrophilic, nontoxic in vivo,
      nonantigenic material and had good biocompatibility as a drug carrier. The effect
      on drug release from the polymer of length of side chain, initial drug loading,
      and particle size of the polymer drug were investigated in tris-HCl buffer
      solution (pH 7.4, t = 37 degrees C). In vivo release in rabbits also was
      performed for 120 days. The experiment indicated that the concentration of NET in
      rabbits can be 1-2 microg/ml serum after 1 month; 10% of NET had been released
      from the polymer.

PMID- 12511200
TI  - Floating-bioadhesive microspheres containing acetohydroxamic acid for clearance
      of Helicobacter pylori.
AB  - A new strategy based on gastric retention is proposed for the treatment of
      Helicobacter pylori. (H. pylori). A synergism between a floating and a
      bioadhesive system has been explored. Floating microspheres containing the
      antiurease drug acetohydroxamic acid (AHA) were prepared by a novel quasi
      emulsion solvent diffusion method. The microballons were characterized for size
      distribution, morphology, drug content, drug release, and in vitro floating
      property. The microballons were coated with 2% w/v solution of polycarbophil by
      the air suspension coating method. The bioadhesive property of the microspheres
      was investigated by the detachment force measurement method. In vitro growth
      inhibition studies were performed in isolated H. pylori culture. The results
      suggest that AHA-loaded floating microspheres are superior as potent urease
      inhibitors whereas urease plays an important role in the colonization of H.
      pylori. We suggest that an oral dosage containing floating-bioadhesive
      microspheres may form a useful drug delivery system for the treatment of H.
      pylori.

PMID- 12511201
TI  - Polymer controlled drug delivery system for growth hormone.
AB  - The use of biomaterials as vehicles for pharmacological agents, hormones, and
      growth factors is at times the best treatment for controlled local
      administration. Our study was designed to evaluate the in vitro biocompatibility
      and potential clinical use of a new polymer, hydroxyethyl methacrylate-vinyl
      pirrolidone. Human fibroblasts were incubated in the presence of the polymer
      and/or growth hormone, and evaluation was made of both the rate of polymer and
      hormone degradation and the proliferative effect on the fibroblast population.
      Results indicate that this polymer is biodegradable and lacks toxicity toward
      these cells. The hormone was slowly released, as suggested by enhanced cell
      proliferation.

PMID- 12511202
TI  - Transdermal delivery of nicardipine: an approach to in vitro permeation
      enhancement.
AB  - Nicardipine hydrochloride (NC-HCl), a calcium channel blocker for the treatment
      of chronic stable angina and hypertension, seems to be a potential therapeutic
      transdermal system candidate, mainly due to its low dose, short half-life, and
      high first-pass metabolism. The objective of the present study was to evaluate
      its flux and elucidate mechanistic effects of formulation components on
      transdermal permeation of the drug through the skin. Solubility of NC-HCl in
      different solvent systems was determined using a validated HPLC method. The
      solubility of drug in various solvent systems was found to be in decreasing order
      as propylene glycol (PG)/oleic acid (OA)/dimethyl isosorbide (DMI) (80:10:10 v/v)
      > PG > PG/OA (90:10 v/v) > polyethylene glycol 300 > ethanol/PG (70:30 w/w) >
      transcutol > dimethyl isosorbide (DMI) > ethanol > water and buffer 4.7 > 2
      propanol. Propylene glycol was then selected as the main vehicle in the
      development of a transdermal product. As a preliminary step to develop a
      transdermal delivery system, vehicle effect on the percutaneous absorption of NC
      HCl was determined using the excised skin of a hairless guinea pig. Vehicles
      investigated included pure solvents alone and their selected blends, chosen based
      on the solubility results. In vitro permeation data were collected at 37 degrees
      C, using Franz diffusion cells. The skin permeation was then evaluated by
      measuring the steady state permeation rate (flux) of NC-HCl, lag time, and the
      permeability constant. The results showed that no individual solvent was capable
      of promoting NC-HCl penetration. Permeation profiles of the drug through hairless
      guinea pig skin using saturated solutions of drug were constructed. Among the
      systems studied, the ternary mixture of PG/OA/DMI and binary mixture of PG/OA
      showed excellent flux. The flux value of the ternary system was nearly three
      times higher than the corresponding values obtained for the binary solvent. A
      similar trend also was observed for the permeation constant, while the values of
      lag time were reversed. The ternary mixture was then selected as a potential
      absorption enhancement vehicle for the transdermal delivery of drug. In general,
      higher fluxes were observed through hairless guinea pig skin as compared with the
      human stratum corneum. Based on the results obtained from the release study of NC
      HCl from saturated solutions of the drug, a novel lecithin organogel
      (microemulsion-based gel) composed of soybean lecithin, propylene glycol, oleic
      acid, dimethyl isosorbide, and isopropyl myristate was developed as a possible
      matrix for transdermal delivery of NC-HCl. In vitro percutaneous penetration
      studies from this newly developed gel system through giunea pig skin and human
      stratum corneum revealed that the organogel system has skin-enhancing potential
      and could be a promising matrix for the transdermal delivery of nicardipine.
      Furthermore, higher permeation rates were observed when nicardipine free base was
      incorporated into the gel matrix instead of hydrochloride salt.

PMID- 12511203
TI  - Effective treatment of bladder tumor-bearing mice by direct delivery of bleomycin
      using electrochemotherapy.
AB  - We investigated the cytotoxicity on the combination of bleomycin (BLM) with
      electric pulses against transplanted bladder tumors in nude mice. Loading with
      high-voltage electric pulse after injection of BLM was associated with a decrease
      in tumor size; tumor size became smaller and disappeared 8 days after the
      treatment. Such complete regression was achieved with one treatment using BLM of
      one-tenth the lethal dose (LD(50)) combined with electric pulses. On day 20,
      regrowth was observed at a much slower rate than at lower concentrations of BLM.
      Pathological examinations of the tumor tissues after treatment revealed
      disruption of the nucleus in the exposed tissues on day 2. Furthermore, a
      decrease in number of the stained nuclei and cytoplasmic lysis were observed on
      day 4. These results showed that electric pulses was an effective tool to deliver
      drugs into bladder tumor cells and an effective treatment method for bladder
      tumors.

PMID- 12511204
TI  - Sequestration and ultrasound-induced release of doxorubicin from stabilized
      Pluronic P105 micelles.
AB  - Controlled drug delivery from micelles requires that the micelles remain stable
      when diluted below their critical micelle concentration, such as upon injection
      into blood. A cross-linked, interpenetrating network of N,N-diethylacrylamide
      (NNDEA) was polymerized in the core of Pluronic P105 micelles to stabilize
      temporarily the micelles at concentrations below the critical micellar
      concentration of free P105. The stabilized Pluronic micelles (called Plurogels)
      were able to sequester the drug doxorubicin (Dox) and protect HL-60 cells from
      the drug at concentrations where non-stabilized Pluronic provided no protection.
      The protection lasted approximately 12 hr, which is similar to the half-life of
      the particles. Application of low-frequency ultrasound resulted in a synergistic
      killing effect with Dox and low concentrations of either Pluronic P105 or
      stabilized Plurogels, most probably due to release of Dox and permeabilization of
      the cell membrane.

PMID- 12511205
TI  - In vitro permeation screening of a new formulation of thiocolchicoside containing
      various enhancers.
AB  - Thiocolchicoside, a muscle relaxant agent with anti-inflammatory and analgesic
      actions, also is used topically for the treatment of muscular spasms and for
      rheumatologic, orthopedic, and traumatologic disorders. In this study,
      thiocolchicoside was formulated to use as foam to avoid contact with the
      afflicted area during the spreading phase. To enhance drug penetration, various
      enhancers were added to the base formulation. The tested enhancers were
      ethoxyethylendiglycol (Transcutol), highly purified phosphatidylcholine (Lipoid
      S20), capsaicin, propylene glycol dipelargonate (DPPG), and glycolysed
      ethoxylated glycerides (Labrafil M1944 CS). The transdermal absorption of the
      tested formulations containing enhancers, in comparison with base formulation,
      was evaluated in vitro through rat skin using standard Franz diffusion cells.
      Base formulation was found to have a higher permeation profile than the simple
      aqueous and hydroalcoholic solutions of the drug, meaning that the base
      formulation by itself enhances the drug permeation. Among the tested
      formulations, only the formulation containing DPPG/ethanol was found to be
      statistically different, showing an enhancement factor of 3.58. In the same
      experimental session, Muscoril ointment, the commercially available
      pharmaceutical product containing the same thiocolchicoside concentration
      (0.25%), also was tested. The formulation containing DPPG/ethanol showed a 4.86
      times increase of permeability constant in comparison with Muscoril ointment. The
      formulation containing DPPG/ethanol as an enhancer could be a good candidate for
      a new topical foam, considering its good characteristics of permeability and
      compliance.

PMID- 12511208
TI  - The efficacy of a psychosocial intervention for HIV/AIDS caregiving dyads and
      individual caregivers: a controlled treatment outcome study.
AB  - The present study examined the comparative efficacy of intervening at the
      caregiver/care-recipient dyadic level, versus the individual caregiver level, for
      caregivers and their care-recipients with HIV/AIDS. Participants were randomly
      assigned to a Dyad Intervention (DI), a Caregiver Intervention (CI) or Wait List
      Control group (WLC), and assessed by interview and self-administered scales
      immediately before treatment and eight weeks later. Participants in the
      intervention groups also completed a four-month follow-up assessment. Dependent
      variables included global distress, social adjustment, dyadic adjustment,
      subjective health status, HIV/AIDS knowledge and target problem ratings. Results
      showed that caregivers in the DI group showed greater improvement from pre- to
      post-treatment on global distress, dyadic adjustment and target problems than the
      CI and WLC caregivers. The CI and DI caregivers showed greater improvement than
      the WLC group on all dependent variables except social adjustment. Care
      recipients in the DI group improved significantly from pre- to post-treatment on
      dyadic adjustment, social adjustment, knowledge, subjective health status and
      Target Problem 1, whereas the CI and WLC care-recipients failed to improve on any
      of these measures. The treatment gains made by the DI caregivers and care
      recipients on most dependent variables were maintained at a four-month follow-up.
      Findings support a reciprocal determinism approach to the process of dyadic
      adjustment and suggest that intervening at the caregiver/care-recipient level may
      produce better outcomes for both the caregiver and care-recipient than
      intervening at the individual caregiver level.

PMID- 12511209
TI  - Self-care management for neuropathy in HIV disease.
AB  - Peripheral neuropathy is the most common neurological complication in HIV and is
      often associated with antiretroviral therapy. As part of a larger study on self
      care for symptoms in HIV disease, this study analyzed the prevalence and
      characteristics of peripheral neuropathy in HIV disease, the self-care
      strategies, and sources of information for self-care utilized by the sample. A
      convenience sample of 422 respondents was recruited from an Internet web-based
      site developed by the University of California, San Francisco International
      HIV/AIDS Research Network and from five geographic data collection sites (Boston,
      New York City, San Francisco and Paterson in the USA, and Oslo, Norway). Results
      of the study indicated that respondents with peripheral neuropathy identified 77
      self-care behaviours including complementary therapies, use of medications,
      exercise and rest and/or elevation of extremities. Sources of information
      included health care providers, informal networks and media sources.

PMID- 12511210
TI  - Improving the accessibility of condoms in South Africa: the role of informal
      distribution.
AB  - Lack of access to condoms presents a fundamental barrier to HIV prevention across
      most of sub-Saharan Africa. One strategy to enhance the accessibility of condoms
      is to promote their informal distribution outside of health facilities through
      existing social networks. To investigate the prevalence and practices of informal
      condom distribution, we administered a questionnaire to individuals procuring
      condoms at 12 public health facilities in four regions of South Africa. Of the
      554 individuals interviewed, 269 (48%) reported either giving or receiving
      condoms informally in the month before the study. In multivariate analysis,
      reporting informal condom distribution was associated with increased education,
      male gender, multiple sex partners and recent condom use. The specific practices
      involved in giving or receiving condoms differed between males and females, with
      women more likely to involve family members and men more likely to involve
      friends. These results indicate that informal condom distribution is surprisingly
      common among individuals procuring public sector condoms in South Africa, and
      begin to suggest the gendered nature of informal condom distribution networks.
      While these findings require confirmation in other populations, the practices of
      informal condom distribution described here provide an excellent opportunity for
      enhancing condom accessibility and delivering other interventions for HIV
      prevention.

PMID- 12511211
TI  - Ineffective use of condoms among young women in managed care.
AB  - Condoms must be used effectively in order to prevent pregnancy and the spread of
      HIV/STD. This study investigated two types of ineffective condom use, delayed
      condom use (initiated after penetration has occurred) and condom slippage and/or
      breakage. We estimated prevalence and identified predictors of ineffective condom
      use among young women at risk of STDs. The study used baseline survey data from a
      randomized trial of women 18-24 years old at two managed care sites; 779
      participants who were recent condom users were included in this analysis. Forty
      four per cent of the sample reported delayed condom use in the past three months
      and 19% reported condom slippage and/or breakage. In multivariate logistic
      regression, younger age, primary partner, lack of partner support, multiple
      recent sexual partners and using condoms for contraception were positively
      associated with delayed condom use. Correlates of condom slippage and/or breakage
      were non-white race/ethnicity and history of any STD. Greater frequency of condom
      use independently predicted both outcomes. Ineffective condom use was common in
      this sample of experienced condom users and predictors were different for each
      outcome. HIV/STD prevention interventions must address more specific aspects of
      condom use than have previously been their focus, especially when condom use is
      already high.

PMID- 12511212
TI  - Relationship power, condom use and HIV risk among women in the USA.
AB  - Women's ability to negotiate safer sexual practices, particularly condom use, is
      a vital component of HIV/STD prevention strategies. Gender-based power imbalances
      may constrain women's negotiation ability, yet few empirical studies have tested
      the hypothesis that sexual relationship power constitutes a key factor in condom
      use negotiation. In this investigation, a new measure - the Sexual Relationship
      Power Scale (SRPS) - was applied. Data were collected from 388, mostly Latina,
      women at an urban community health centre in Massachusetts. Women with high
      levels of relationship power were five times as likely as women with low levels
      to report consistent condom use, after controlling for sociodemographic and
      psychosocial variables (p < 0.05). Population attributable risk estimates
      indicate that 52% of the lack of consistent condom use among women can be
      attributed to low sexual relationship power. The strong association between the
      Sexual Relationship Power Scale and consistent condom use supports the hypothesis
      that relationship power plays a key role in safer sex decision making. These
      findings underscore the importance of including the issue of relationship power
      in the design and implementation of programmes that promote sexual and
      reproductive health, as well as research investigating condom use and HIV risk.

PMID- 12511213
TI  - Sex partner support, drug use and sex risk among HIV-negative non-injecting
      heroin users.
AB  - HIV prevention efforts among drug users have incorporated social support to
      reinforce risk reduction. We examine the extent to which sex partner
      characteristics, including partner support, influence HIV sex risk practices
      among a little studied population of non-injecting heroin users, 257 of whom were
      recruited in New York City between 1996 and 2001. The sample was
      racially/ethnically diverse (26% African American, 43% Latino, 31% white or other
      ethnicity) and 65% male. Three-quarters reported having unprotected intercourse
      within 30 days; 27% had sex with partners at known risk of being HIV infected.
      There were no gender differences in terms of sex or drug use practices; however,
      gender differences in sex partner characteristics were apparent. Men were
      significantly less likely than women to have partners who used drugs (OR = 0.5,
      95% CI = 0.3, 0.9), receive support from their partners (OR = 0.5, 95% CI = 0.3,
      0.8), use heroin with their partners (OR = 0.5, 95% CI = 0.3, 0.8) and have
      partners at known risk of being HIV infected (OR = 0.4, 95% CI = 0.2, 0.7). For
      men, increased sex risk was independently associated with sex partner support,
      and for women, increased sex risk was independently associated with having used
      heroin with sex partners. Social support may have detrimental, as well as
      beneficial, consequences on HIV risk.

PMID- 12511214
TI  - Sexual and drug-using practices of HIV-positive men who frequent public and
      commercial sex environments.
AB  - An ethnically diverse sample (69.7% men of colour) of HIV-seropositive MSM from
      the New York City and San Francisco metropolitan areas were recruited from a
      variety of social settings. While only 27.0% of the participants were recruited
      from PSEs (public sex environments where men 'cruise' for potential sex partners,
      such as parks) and CSEs (commercial sex environments where an admission is paid
      for entrance, such as bathhouses and sex clubs), 49.6% reported attending PSEs
      and 40.7% reported attending CSEs. Only a minority of participants from the full
      sample reported sexual behaviours that would have placed a partner at highest
      risk for HIV seroconversion. However, differences between those who frequented
      CSEs and those who did not emerged on several psychosocial factors (sexual
      sensation seeking, depression, perceived responsibility towards protecting sexual
      partners from HIV infection), sexual risk behaviours (unprotected oral and anal
      sex) and types of recreational drugs used. Fewer differences were found between
      those who frequented PSEs and those who did not.

PMID- 12511215
TI  - Improving safer sex measures through the inclusion of relationship and partner
      characteristics.
AB  - This article describes the development of a safer sex algorithm, which considers
      the characteristics of a woman's relationship and the HIV risk profile of herself
      and her primary partner. A sample of 306 low-income, predominantly African
      American women was recruited to participate in a study of the effectiveness of a
      sexual health seminar. These women were interviewed three times, at one month
      prior to seminar administration, three months after the seminar and again nine
      months after the seminar. Data from these women indicate that using an algorithm
      that considers the probability of HIV transmission between partners decreases the
      measured prevalence of unsafe sex in this population by about 17% and lowers the
      estimate of the average number of unsafe incidents by about four incidents in
      three months. The algorithm results in measures with adequate levels of temporal
      stability, which are similar to the more commonly used measure, vaginal or anal
      intercourse without a condom.

PMID- 12511216
TI  - Rearrest: does HIV serostatus make a difference?
AB  - Correctional facilities have become collection and containment centres for HIV
      seropositive individuals. This is due to factors that affect incarceration in
      general: past criminal behaviour, age and crime type. In addition, the sex trade
      industry, intravenous drug use and community instability are likely factors
      affecting this particular population. The objective of this study was to
      determine whether HIV-positive offenders have higher rates of rearrest than HIV
      negative offenders. A sample of HIV-positive offenders (n = 57) were seen for
      mental health evaluation at the King County Correctional Facility (KCCF) in
      Seattle Washington. They were compared to a historical sample (n = 254) of HIV
      negative individuals also from the KCCF. After three months, 50% of both samples
      had been rearrested. Using the log rank test in Kaplan-Meier survival analysis,
      statistical difference in the relative risk of rearrest occurred for the HIV
      positive group (logrank = 0.03). Statistical adjustment for mental illness, age,
      race, ethnicity, substance abuse history and past criminal history did not affect
      rearrest significantly. Nonetheless, HIV-positive individuals who presented with
      mental health needs appeared to be significantly more vulnerable to rearrest
      after the first three months of release into the community.

PMID- 12511217
TI  - Investigating the psychosocial impact of anti-HIV combination therapies.
AB  - Developments in anti-HIV medication have meant that people with HIV/AIDS are now
      living longer, with some authors arguing that HIV should now be defined as a
      manageable rather than terminal illness. However uncertainty about the long-term
      efficacy of such treatments remains. This research aimed to examine the
      psychosocial impact of the new treatments and to explore whether, and in what
      ways, they affect psychological wellbeing. Clients were also asked about their
      use of services and whether they thought services should be changing in response
      to new pharmacological treatments. A semi-structured interview schedule was
      developed to elicit the views of six service users. From multiple readings of the
      qualitative data generated, prominent themes were identified suggesting that
      participants had ambivalent feelings about taking antiretroviral combination
      therapy and that being well with HIV raised a number of difficult issues. Four
      main themes were revealed: (1) disruptions in daily living: antiretrovirals as
      intrusions to life, (2) the tablets as a visible marker for HIV infection, (3)
      tempered optimism and increasing horizons, (4) an uncertain and fragile future:
      life without benefits and services. The results were discussed in terms of
      limitations of the current study and suggestions for further research.

PMID- 12511218
TI  - Introduction of voluntary counselling and rapid testing for HIV in rural South
      Africa: from theory to practice.
AB  - Expanding access to voluntary counselling and testing (VCT) for HIV is an
      important first step in the development of a comprehensive package of HIV
      services. This article describes the introduction of VCT among five primary
      health care (PHC) facilities in a rural South African setting, alongside a
      multidimensional impact assessment as part of a national pilot programme. A
      baseline review of services demonstrated low levels of VCT, which were
      predominantly hospital-based. Twenty health workers in five PHC facilities were
      trained to provide VCT using rapid-testing assays. The feasibility of VCT
      introduction and its overall acceptability to clients and providers were
      evaluated using clinic testing registers, semi-structured interviews with
      counsellors and mock client encounters. One year after its introduction, a major
      increase in the quantity of HIV testing, the proportion of clients who receive
      their results, and the proportion who present voluntarily was observed. The
      majority of those presenting were women, and 20-40 year olds predominated. There
      was a high level of acceptance among health workers, and the quality of VCT was
      rated very good in mock client encounters. This work demonstrates one effective
      model for improving access to VCT through existing primary health care services
      in a rural South African context.

PMID- 12511223
TI  - Lyon genetically hypertensive rats: an animal model of "low renin hypertension".
AB  - This paper reviews the data which demonstrate that Lyon genetically hypertensive
      (LH) rats exhibit a low renin form of hypertension. Since when compared to
      normotensive controls, LH rats exhibit a low renin release and are salt
      sensitive. Despite this, the blockade of the renin-angiotensin system normalizes
      the blood pressure level and the regional blood flows in LH rats. Such a
      discrepancy between the compulsory presence of angiotensin II for the
      hypertension to develop and the low level of renin release seen in LH rats led to
      two hypotheses: 1) the existence of an early, short lasting increase of renin
      release which would be sufficient for the occurrence of a stable hypertension; 2)
      an hypersensitivity to the effects of angiotensin II. The study of the long-term
      effects of early short lasting blockades of the renin-angiotensin system allowed
      to exclude the first hypothesis. Concerning a hypersensitivity to the effects of
      angiotensin II, it was found to exist in the preglomerular vessels of LH rats.
      This increased response of renal vessels to angiotensin II may well explain the
      low renin form of hypertension of our model and therefore represents an important
      field for further research.

PMID- 12511224
TI  - Recent advances in traditional plant drugs and orchids.
AB  - The main objective of this paper is to review recent advances in plant drug
      research and developments in orchid study, in an attempt to provide useful
      references for plant drug studies. Plants have been used as medicine for
      millennia. Out of estimated 250 000 to 350 000 plant species identified so far,
      about 35 000 are used worldwide for medicinal purposes. It has been confirmed by
      WHO that herbal medicines serve the health needs of about 80 percent of the
      world's population; especially for millions of people in the vast rural areas of
      developing countries. Meanwhile, consumers in developed countries are becoming
      disillusioned with modern healthcare and are seeking alternatives. The recent
      resurgence of plant remedies results from several factors: 1) the effectiveness
      of plant medicines; 2) the side effect of most modern drugs; and 3) the
      development of science and technology. It has been estimated that in the mid
      1990s over 200 companies and research organizations worldwide are screening plant
      and animal compounds for medicinal properties. Actually, several important drugs
      used in modern medicine have come from medicinal plant studies, eg,
      taxol/paclitaxel, vinblastine, vincristine, topotecan, irinotecan, etoposide,
      teniposide, etc. As for drugs derived from orchids, some novel discoveries, both
      in phytochemical and pharmacological properties, were reported by some
      universities. However, studies on plants are very limited. Only about a third of
      the million or so species of higher plants have been identified and named by
      scientists. Of those named, only a tiny fraction has been studied. Nowadays the
      linking of the indigenous knowledge of medicinal plants to modern research
      activities provides a new approach, which makes the rate of discovery of drugs
      much more effective than with random collection.

PMID- 12511225
TI  - Ion-channels in human sperm membrane and contraceptive mechanisms of male
      antifertility compounds derived from Chinese traditional medicine.
AB  - Ion channel plays a key role in maturation, capacitation and acrosome reaction of
      sperm. However, as it is difficult to record channel currents from a mature
      mammal sperm directly by patch-clamp technique, there were no basic data on the
      types and properties of the channels in human sperm until the method
      reconstituting the channels into bilayer was used. By reconstituting the channel
      proteins isolated from sperm membrane into phospholipid-forming bilayer, we have
      characterized several kinds of Ca2+-, Na+-, K+-, and Cl--permeable channels with
      different conductance and properties in human sperm membrane. To study the
      channels in spermatogenic cells is another approach to understand the ion
      channels in mature sperm. The cell is used as a model to analyze the effects of
      male antifertility agents on Ca2+-channel. To date, several male contraceptives
      derived from Chinese traditional medicine have been attached worldwide interest,
      a lot of compounds have been purified from them, and the antifertility effects of
      some compounds were demonstrated. We studied the effects of gossypol and several
      compounds isolated from Tripterygium wilffordii on Ca2+ channel in mouse
      spermatogenic cells and found that each of them inhibited the channel and sperm
      acrosome reaction at a proximate concentration, suggesting that the inhibition of
      Ca2+ channels may be one mechanism of the antifertility effects of these
      contraceptives.

PMID- 12511226
TI  - Calcium-dependent synergistic interaction of platelet activating factor and
      epinephrine in human platelet aggregation.
AB  - AIM: To investigate the mechanism (s) involved in the synergistic interaction of
      platelet activating factor (PAF) and epinephrine. METHODS: Blood was obtained
      from healthy human subjects reported to be free of medications for at least two
      weeks before sampling. Aggregation was monitored at 37 oC using Dual-channel Lumi
      aggregometer. The resulting aggregation was recorded for 5 min by the measurement
      of light transmission as a function of time. RESULTS: Platelet aggregation
      mediated by subthreshold concentrations of PAF (5-8 nmol/L) plus epinephrine (0.5
      2 micromol/L) was inhibited by ?2-receptor blocker, yohimbine, and PAF receptor
      antagonist WEB 2086. This synergism was inhibited by calcium channel blockers,
      verapamil and diltiazem. In addition, platelet aggregation by co-addition of PAF
      and epinephrine was also inhibited by very low concentrations of phospholipase C
      (PLC) inhibitor (U73122; IC50=0.2 micromol/L), the MAP kinase inhibitor, PD 98059
      (IC50=3 micromol/L), and cyclooxygenase (COX-1) inhibitors including indomethacin
      (IC50=0.25 micromol/L), flurbiprofen (IC50=0.7 micromol/L), and piroxicam (IC50=7
      micromol/L). However, COX-2 inhibitors, nimesulide (IC50=26 micromol/L), NS-398
      (IC50=7 micromol/L), and etodolac (IC50=15 micromol/L) were also effective in
      inhibiting the aggregation. The inhibitors of protein kinase C (chelerythrine)
      and tyrosine kinase (genistien), and phosphatidylinositol 3-kinase inhibitor
      (wortmannin) had no significant effect on platelet aggregation induced by PAF and
      epinephrine. CONCLUSION: The synergistic effect of PAF and epinephrine on human
      platelet aggregation is receptor-mediated and involves the activation of
      PLC/Ca2+, COX and MAP kinase signalling pathways.

PMID- 12511227
TI  - Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic
      arrhythmia in isolated rat heart.
AB  - AIM: To observe the effects of endothelin receptor subtype A (ETA) and B (ETB)
      antagonists on acute ischemic arrhythmia in isolated rat heart, and to determine
      whether endogenous endothelin (ET) was implicated in the pathophysiological
      process of arrhythmia induced by acute myocardial ischemia. METHODS: Fifty-three
      SD male rats were randomized into 8 groups. Heart was isolated and perfused in
      Langendorff mode and acute ischemia model was established by ligation of the left
      anterior descending (LAD) coronary artery. The effects of ETA receptor antagonist
      PD156707 and ETB receptor antagonist IRL1038 on arrhythmia, heart function, the
      myocardial activity of superoxide dismutase (SOD), and the content of
      melondialdehyde (MDA) during the acute 60-min ischemic phase were analyzed.
      RESULTS: Pretreatment with PD156707 (20-500 nmol/L) dose-dependently improved the
      ischemic isolated heart function, enhanced SOD activity and decreased MDA content
      in the ischemic myocardium, and suppressed the acute ischemic arrhythmia.
      Conversely pretreatment with IRL1038 did not change the heart function, SOD
      activity, MDA content, and the acute ischemic arrhythmia significantly as
      compared with the occlusion control. CONCLUSION: ETA receptor antagonist
      effectively improved heart function, enhanced anti-oxidative function of the
      myocardium and reduced arrhythmia during the acute ischemic phase in isolated rat
      hearts, while ETB receptor antagonist did not exert protective effects,
      suggesting that endogenous ET-1, acting through ETA receptor, may be one of the
      factors implicated in arrhythmia and impairment to heart function during the
      acute ischemic phase.

PMID- 12511228
TI  - Effect of ghrelin on septic shock in rats.
AB  - AIM: To study the role of ghrelin in the late stage of septic shock in rats.
      METHODS: The rat model of septic shock was made by caecal ligation and
      perforation. At the time of operation ghrelin 10 nmol/kg was infused through
      femoral vein followed by a sc injection at 8 h after operation. Hemodynamic
      parameters including heart rate (HR), mean arterial blood pressure (MABP),
      LVdp/dtmax, and left ventricular end-diastolic pressure (LVEDP) in survival rats
      were measured at 18 h after surgery. Plasma glucose and lactate concentrations,
      plasma ghrelin level and myocardial ATP content were assayed. The mortality rate
      in rats with septic shock was also observed. RESULTS: Compared to that of septic
      shock group, MABP of rats in ghrelin-treated group increased by 33 % (P <0.01).
      The values of +LVdp/dtmax and -LVdp/dtmax increased by 27 % and 33 %,
      respectively (P <0.01), but LVEDP decreased by 33 % (P < 0.01). The plasma
      glucose concentration and myocardial ATP content increased by 53 % and 22 %,
      respectively, but plasma lactate concentration decreased by 40 % in ghrelin
      treated rats (P < 0.01). The plasma ghrelin level in rats with septic shock was
      51 % higher than that of rats in sham group, and was negatively correlated with
      MABP and blood glucose concentration (r=-0.721 and -0.811, respectively, P
      <0.01). The mortality rates were 47 % (9/19) in rats with septic shock and 25 %
      (3/12) in rats of ghrelin-treated group, respectively. CONCLUSION: Treatment with
      ghrelin could correct partly the abnormalities of hemodynamics and metabolic
      disturbance in septic shock of rats.

PMID- 12511229
TI  - Hypoglycemic activity of ginseng glycopeptide.
AB  - AIM: To study the hypoglycemic activity of ginseng glycopeptide (GGP). METHODS:
      Normal mice or rabbits and alloxan or streptozotocin-induced hyperglycemic rats
      or mice were used in the study. Blood glucose and liver glycogen levels of the
      experimental animals during the trial period were analyzed by spectrophotometry
      with O-toluidine and iodine reagents, respectively. RESULTS: Significant
      decreases in blood glucose and liver glycogen levels were induced in a dose
      dependent manner after administration of GGP 50, 100, or 200 mg/kg injected ip or
      sc to normal mice and injected im 30 or 60 mg/kg to normal rabbits. The
      hypoglycemic activity of GGP lasted for about 16 h, and were examined in both
      normal animals and hyperglycemic animals. CONCLUSION: GGP injection induced the
      pronounced decreases in blood glucose and liver glycogen levels in both normal
      and hyperglycemic animals.

PMID- 12511230
TI  - Metformin modulates insulin post-receptor signaling transduction in chronically
      insulin-treated Hep G2 cells.
AB  - AIM: To study the effect of chronic insulin treatment on insulin post-receptor
      signaling transduction and whether the effects of metformin are transmitted
      throughout the cascade of insulin signaling intermediates in a human hepatoma
      cell line (Hep G2). METHODS: Hep G2 cells were incubated in serum free media
      containing either insulin 100 nmol/L or insulin 100 nmol/L plus different
      concentrations (0.01-10 mmol/L) of metformin for 16 h and then were stimulated
      with insulin 100 nmol/L for 1 min. RESULTS: Chronic treatment of insulin 100
      nmol/L induced a significant reduction in the phosphorylation and protein
      expression of IR?, IRS1 and IRS2, which therefore resulted in a downregulation of
      association of PI3K with IRS. Therapeutic concentrations (0.01-0.1 mmol/L) of
      metformin prevented the changes induced by chronic insulin treatment in these
      post-receptor components of insulin signaling pathway. Tyrosine phosphorylation
      of IR?, IRS1, and IRS2 was increased by 2.7 fold (P < 0.01), 6.8 fold (P < 0.01),
      and 2.3 fold (P <0.01) of chronically insulin-treated cells alone, respectively,
      after metformin 0.1 mmol/L was added. The association of p85 with IRS1 and IRS2
      was also increased from 34 % to 86 % (P <0.01) and from 30 % to 92 % (P <0.01),
      respectively. In contrast, metformin in pharmacological concentration (1-10
      mmol/L) further inhibited tyrosine phosphorylation of IR?, IRS1, IRS2 and the
      interaction of PI3K with IRS. The association of IRS1 with p85 was further
      decreased by 58 % (P >0.05) and of IRS2 by 30 % (P <0.05). CONCLUSION: Chronic
      insulin exposure of Hep G2 cells induces the downregulation of insulin signal
      transduction via PI3K pathway. The effect of metformin on insulin signaling
      transduction represent a primary mechanism of metformin action in insulin
      resistant state.

PMID- 12511231
TI  - Hypoglycemic mechanism of ginseng glycopeptide.
AB  - AIM: To study the hypoglycemic mechanism of ginseng glycopeptide (GGP). METHODS:
      After administration of GGP, the levels of insulin, lactate dehydrogenase (LDH),
      lactic acid (LC), and oxygen consumption, as well as blood glucose (BG) and liver
      glycogen (LG) were measured. Based on these measurement results, the effects of
      GGP on insulin secretion and anaerobic/aerobic glycolysis were evaluated.
      Adenylate cyclase (AC) activity and cAMP level were measured to study the effects
      of GGP on BG and LG metabolism and to determine whether the effects were through
      second transmitting message system. Propranolol (beta-receptor antagonist) and
      phentolamine (alpha-receptor antagonist) were used to investigate whether
      hypoglycemic activity of GGP was through beta- or alpha-adrenoceptor. [3H]DHA
      (antagonist of beta-adrenoceptor) was used to determine GGP binding affinity to
      beta-adrenoceptor. Citrate synthetase (CTS), succinate dehydrogenase (SDH),
      malate dehydrogenase (MDH), and cytochrome oxidase (CCO) activities were measured
      to explore GGP effects on aerobic glycolysis in liver mitochondria. Phosphorylase
      (PP) activity was measured to study GGP effects on liver glycogen metabolism.
      RESULTS: cAMP content and AC activity were increased when BG and LG contents in
      liver of mice decreased. The decrease in liver glycogen induced by GGP was
      inhibited by pretreatment with propranolol. Radioligand receptor assay showed
      that GGP was competing in vitro with [3H]DHA to bind to beta-adrenoceptor of duck
      erythrocyte membrane, and IC50 of GGP was 63 nmol/L. GGP inhibited LDH activity
      at an appropriate dosage, at which contents of BG and LG could be effectively
      lowered. GGP also stimulated activities of SDH, MDH, CCO, CTS, and PP.
      CONCLUSION: The hypoglycemic activity of GGP may be attributed to the enhancement
      of aerobic glycolysis through stimulation of beta-adrenoceptor and increase of
      various rate-limiting enzyme activities related to tricarboxylic acid cycle.

PMID- 12511232
TI  - Mechanisms of irbesartan in prevention of renal lesion in streptozotocin-induced
      diabetic rats.
AB  - AIM: To investigate the mechanisms of angiotensin II receptor antagonist
      irbesartan (Irb) in prevention of renal lesion in streptozotocin (STZ)-induced
      diabetic rats. METHODS: Sprague-Dawley (SD) rats were randomly divided into three
      groups: normal control (group N), diabetic nephropathy (group DN), and diabetic
      nephropathy treated with Irb (group DNI). Diabetes was induced by injection of
      STZ ip after rats had received uninephrectomy. Blood glucose (BG), body weight
      (BW), urinary albumin excretion (Ualb), and 24-h proteinuria (24hUpro) were
      observed in the rats at week 4, 8, and 12, respectively. Creatinine clearance
      (Ccr), the kidney weight (KW), profile of kidney hypertrophy (KW/BW), renal
      tissue protein contents (RTP), glomerular area (AG), glomerular volume (VG), and
      width of glomerular basement membrane (GBM) were determined after the rats were
      sacrificed at week 12. Renal expression of connective tissue growth factor (CTGF)
      and transforming growth factor-beta1 (TGF-beta1) were determined by
      immunohistochemistry. RESULTS: There was no significant difference in BG between
      group DN and DNI (P >0.05). Irb prevented the increasing of Ualb excretion, 24
      hUpro, and Ccr in diabetic rats ( P < 0.01). Furthermore, Irb markedly inhibited
      the increasing of KW, KW/BW, RTP, AG, and VG shown in diabetic rats (P <0.05, P
      <0.01, respectively). Irb prevented the thickening of GBM and immunostaining of
      CTGF (P <0.01). The extent of CTGF expression was positively correlated with the
      glomerular immunostaining for TGF-beta1 and size of VG (P <0.01). CONCLUSION: Irb
      exerts an early renal protective role to diabetic nephropathy, possibly through
      inhibition of renal hypertrophy and expression of CTGF.

PMID- 12511233
TI  - Quantitative determination of omapatrilat and its metabolites in human plasma by
      HPLC coupled with tandem mass spectrometry.
AB  - AIM: To develop a sensitive and specific analytical method for the quantitative
      determination of omapatrilat (BMS-186716) and its metabolites (BMS-196087,
      225308, 198433, and 253653) in human plasma. METHODS: Methyl acrylate (MA) was
      selected to react with BMS-186716, 196087, and 253653 to protect the free
      sulfhydryl groups. High pressure liquid chromatography-tandem mass spectrometry
      (HPLC-MS/MS) was used to detect the analytes. RESULTS: The method was validated
      over the concentration range of 0.2-250 microg/L for BMS-186716, 0.5-250 microg/L
      for BMS-196087, 1-250 microg/L for BMS-225308, 2-250 microg/L for BMS-198433, and
      10-2500 microg/L for BMS-253653. The limit of quantitation was in turn 0.2, 0.5,
      1, 2, and 10 microg/L, respectively. The extraction recovery was on average 60.5
      %, 88.6 %, 76.3 %, 71.2 %, and 26.6 %, respectively. Inter- and intra-day
      precision of quality control samples (QC) was all within 15 % and accuracy was
      within 85 %--115 %. The analytes in human plasma were found to be stable after
      three cycles of freeze-thaw and for at least 6 h at room temperature (25 oC). No
      significant change was found in reconstituted reagent after 24 h at room
      temperature and results of long-term stability showed all the analytes in human
      plasma were stable for at least 3 months at -30 oC freezing condition.
      CONCLUSION: This method is rapid, sensitive and specific for the pharmacokinetics
      study of omapatrilat and its metabolites.

PMID- 12511234
TI  - Stereoselectivity in trans-tramadol metabolism and trans-O-demethyltramadol
      formation in rat liver microsomes.
AB  - AIM: To study the stereoselectivity in trans-tramadol [(+/-)-trans-T] metabolism
      and trans-O-demethyltramadol (M1) formation. METHODS: (+)-, (-)-, Or (+/-)-trans
      T was separately incubated with rat liver microsomes in vitro. The concentrations
      of (+/-)-trans-T and M1 enantiomers were determined by high performance capillary
      electrophoresis (HPCE). RESULTS: When each enantiomer of (+/-)-trans-T was
      incubated with rat liver microsomes, the metabolic rate of (+)-trans-T was lower
      than that of (-)-trans-T. The kinetics of (+)-, (-)-M1 formation was found to fit
      the single-enzyme Michaelis-Menten model. The Vmax and CLint of (+)-M1 formation
      were lower than those of (-)-M1 formation. When (+/-)-trans-T was used as the
      substrate, the metabolic rates of (+)-, (-)-trans-T, and the formation rates of
      (+)-M1, (-)-M1 decreased to different extents. Dextromethorphan (Dex),
      propafenone (Pro), and fluoxetine (Flu) could inhibit both the metabolism of (+/
      )-trans-T enantiomers and the formation of M1 enantiomers. Pro and Flu were shown
      to enhance the stereoselectivity in both (+/-)-trans-T metabolism and M1
      formation, and Dex could only enhance that in M1 formation. CONCLUSION: (+/-)
      Trans-T metabolism and M1 formation were stereoselective, (-)-trans-T being
      preferentially metabolized and (-)-M1 being preferentially formed. There was
      interaction in metabolism between (+/-)-trans-T enantiomers. Dex, Pro, and Flu
      had different effects on the stereoselectivity.

PMID- 12511235
TI  - Antisense Sp1 oligodeoxynucleotide decreases telomerase activity by inhibiting
      hTERT mRNA expression in Jurkat T cells.
AB  - AIM: To study the effects of transcriptional factor Sp1 antisense
      oligodeoxynucleotide (ODN) on telomerase activity and human telomerase reverse
      transcriptase (hTERT) expression. METHODS: Antisense oligodeoxynucleotide (ODN)
      was designed to inhibit Sp1 expression and transferred to Jurkat T cells by
      lipofectamin. Telomerase PCR-ELISA was used to detect telomerase activity. RT-PCR
      analysis was used to assess the mRNA expression of Sp1 and hTERT, and Western
      blot was used to analyze the levels of Sp1 protein. RESULTS: Treatment of Jurkat
      T cells with Sp1 antisense ODN (1 micromol/L) dramatically reduced Sp1 mRNA and
      protein levels. The inhibition rate was 44.8 % (P <0.05) and 57 % (P <0.01),
      respectively. Following the transcriptional factor Sp1 functionally altering,
      hTERT mRNA expression were suppressed with a 43.7 % inhibition rate (P <0.01). A
      dose-dependent inhibition of telomerase activity by antisense Sp1 ODN was also
      discovered. From 0.25 to 2.0 micromol/L, telomerase activity was reduced from
      27.1 % to 64.6 %. CONCLUSION: Antisense Sp1 ODN decreases telomerase activity by
      inhibiting hTERT mRNA expression in Jurkat T cells.

PMID- 12511299
TI  - Enhanced photo- and antioxidative protection, and hydrogen peroxide accumulation
      in drought-stressed Cistus clusii and Cistus albidus plants.
AB  - Mechanisms of drought stress resistance were studied in Cistus clusii Dunal and
      Cistus albidus L., two native Mediterranean shrubs that can withstand severe
      summer drought. While water deficit, solar radiation and temperature increased
      from winter to summer in the field, C. clusii and C. albidus reduced leaf area,
      increased root mass per leaf area, and showed diurnal changes in stomatal
      conductance to minimize water loss. In both species, the consequent reductions in
      CO2 assimilation were accompanied by reduced efficiency of photosystem II
      photochemistry, and protection against stress was afforded by enhanced de
      epoxidation of violaxanthin in the xanthophyll cycle and increases in alpha
      tocopherol and beta-carotene. In addition, hydrogen peroxide (H2O2) accumulation
      was observed in mesophyll cell walls of both species during the first stages of
      drought, although no accumulation of H2O2 was observed in chloroplasts or other
      organelles during the study. Despite these common responses, C. albidus and C.
      clusii differed in the extent of photo- and antioxidative protection. In response
      to drought, C. clusii showed a higher de-epoxidation state of the xanthophyll
      cycle and higher alpha-tocopherol and beta-carotene concentrations than C.
      albidus. We conclude that several structural and biochemical mechanisms underlie
      stress resistance in C. clusii and C. albidus, and are indicative of the
      different degrees of stress resistance of these shrubs.

PMID- 12511300
TI  - Sapwood development in Pinus radiata trees grown for three years at ambient and
      elevated carbon dioxide partial pressures.
AB  - Clonal trees of Pinus radiata D. Don were grown in open-top chambers at a field
      site in New Zealand for 3 years at ambient (37 Pa) or elevated (65 Pa) carbon
      dioxide (CO2) partial pressure. Nitrogen (N) was supplied to half of the trees in
      each CO2 treatment, at 15 g N m-2 in the first year and 60 g N m-2 in the
      subsequent 2 years (high-N treatment). Trees in the low-N treatment were not
      supplied with N but received the same amount of other nutrients as trees in the
      high-N treatment. In the first year, stem basal area increased more in trees
      growing at elevated CO2 partial pressure and high-N supply than in control trees,
      suggesting a positive interaction between these resources. However, the relative
      rate of growth became the same across trees in all treatments after 450 days,
      resulting in trees growing at elevated CO2 partial pressure and high-N supply
      having larger basal areas than trees in the other treatments. Sapwood N content
      per unit dry mass was consistently about 0.09% in all treatments, indicating that
      N status was not suppressed by elevated CO2 partial pressure. Thus, during the
      first year of growth, an elevated CO2 partial pressure enhanced carbon (C) and N
      storage in woody stems, but there was no further stimulus to C and N deposition
      after the first year. The chemical composition of sapwood was unaffected by
      elevated CO2 partial pressure, indicating that no additional C was sequestered
      through lignification. However, independent of the treatments, early wood was 13%
      richer in lignin than late wood. Elevated CO2 partial pressure decreased the
      proportion of sapwood occupied by the lumina of tracheids by up to 12%,
      indicating increased sapwood density in response to CO2 enrichment. This effect
      was probably a result of thicker tracheid walls rather than narrower lumina.

PMID- 12511301
TI  - Chlorophyll content in eucalypt vegetation at the leaf and canopy scales as
      derived from high resolution spectral data.
AB  - The physiological status of forest canopy foliage is influenced by a range of
      factors that affect leaf pigment content and function. Recently, several indices
      have been developed from remotely sensed data that attempt to provide robust
      estimates of leaf chlorophyll content. These indices have been developed from
      either hand-held spectroradiometer spectra or high spectral resolution (or
      hyperspectral) imagery. We determined if two previously published indices (Datt
      1999), which were specifically developed to predict chlorophyll content in
      eucalypt vegetation by remote sensing at the leaf scale, can be extrapolated
      accurately to the canopy. We derived the two indices from hand-held
      spectroradiometer data of eucalypt leaves exhibiting a range of insect damage
      symptoms. We also derived the indices from spectra obtained from high spectral
      and spatial resolution Compact Airborne Spectrographic Imager 2 (CASI-2) imagery
      to determine if reasonable estimates at a scale of < 1 m can be achieved. One of
      the indices (R 850/R 710 index, where R is reflectance) derived from hand-held
      spectroradiometer data showed a moderate correlation with relative leaf
      chlorophyll content (r = 0.59, P < 0.05) for all dominant eucalypt species in the
      study area. The R (850)/R (710) index derived from CASI-2 imagery yielded
      slightly lower correlations over the entire data set (r = 0.42, P < 0.05), but
      correlations for individual species were high (r = 0.77, P < 0.05). A scaling
      analysis indicated that the R (850)/R (710) index was strongly affected by soil
      and water cover types when pixels were mixed, but appeared to be invariant to
      changes in proportions of understory, which may limit its application.

PMID- 12511302
TI  - Ecophysiology of seedlings of three Mediterranean pine species in contrasting
      light regimes.
AB  - Seasonal dynamics of net photosynthesis (Anet) in 2-year-old seedlings of Pinus
      brutia Ten., Pinus pinea L. and Pinus pinaster Ait. were investigated. Seedlings
      were grown in the field in two light regimes: sun (ambient light) and shade (25%
      of photosynthetically active radiation (PAR)). Repeated measures analyses over a
      12-month period showed that Anet varied significantly among species and from
      season to season. Maximum Anet in sun-acclimated seedlings was low in winter (yet
      remained positive) and peaked during summer. Maximum Anet was observed in June in
      P. pinea (12 micromol m-2 s-1), July in P. pinaster (23 micromol m-2 s-1) and
      August in P. brutia (20 micromol m-2 s-1). Photosynthetic light response curves
      saturated at a PAR of 200-300 micromol m-2 s-1 in winter and in shade-acclimated
      seedlings in summer. Net photosynthesis in sun-acclimated seedlings did not
      saturate at PAR up to 1900 micromol m-2 s-1 in P. brutia and P. pinaster. Minimum
      air temperature of the preceding night was apparently one of the main factors
      controlling Anet during the day. In shade-acclimated seedlings, photosynthetic
      rates were reduced by 50% in P. brutia and P. pinaster and by 20% in P. pinea
      compared with those in sun-acclimated seedlings. Stomatal conductance was
      generally lower in shaded seedlings than in seedlings grown in the sun, except on
      days with a high vapor pressure deficit. Total chlorophyll concentration per unit
      leaf area, specific leaf area (SLA) and height significantly increased in P.
      pinea in response to shade, but not in P. pinaster or P. brutia. In response to
      shade, P. brutia showed a significant increase in total chlorophyll concentration
      but not SLA. Photosynthetic and growth data indicate that P. pinaster and P.
      brutia are more light-demanding than P. pinea.

PMID- 12511303
TI  - Xylem vulnerability to cavitation in Pseudotsuga menziesii and Pinus ponderosa
      from contrasting habitats.
AB  - In the Rocky Mountains, ponderosa pine (Pinus ponderosa (ssp.) ponderosa Dougl.
      ex P. Laws. & C. Laws) often co-occurs with Douglas-fir (Pseudotsuga menziesii
      var. glauca (Mayr) Franco). Despite previous reports showing higher shoot
      vulnerability to water-stress-induced cavitation in ponderosa pine, this species
      extends into drier habitats than Douglas-fir. We examined: (1) whether roots and
      shoots of ponderosa pine in riparian and slope habitats are more vulnerable to
      water-stress-induced cavitation than those of Douglas-fir; (2) whether species
      specific differences in vulnerability translate into differences in specific
      conductivity in the field; and (3) whether the ability of ponderosa pine to
      extend into drier sites is a result of (a) greater plasticity in hydraulic
      properties or (b) functional or structural adjustments. Roots and shoots of
      ponderosa pine were significantly more vulnerable to water-stress-induced
      cavitation (overall mean cavitation pressure, Psi(50%) +/- SE = -3.11 +/- 0.32
      MPa for shoots and -0.99 +/- 0.16 MPa for roots) than those of Douglas-fir
      (Psi(50%) +/- SE = -4.83 +/- 0.40 MPa for shoots and -2.12 +/- 0.35 MPa for
      roots). However, shoot specific conductivity did not differ between species in
      the field. For both species, roots were more vulnerable to cavitation than
      shoots. Overall, changes in vulnerability from riparian to slope habitats were
      small for both species. Greater declines in stomatal conductance as the summer
      proceeded, combined with higher allocation to sapwood and greater sapwood water
      storage, appeared to contribute to the ability of ponderosa pine to thrive in dry
      habitats despite relatively high vulnerability to water-stress-induced
      cavitation.

PMID- 12511304
TI  - Responses of Prunus ferganensis, Prunus persica and two interspecific hybrids to
      moderate drought stress.
AB  - Prunus ferganensis (Kost. & Riab) Kov. & Kost, a close relative of cultivated
      peach (Prunus persica (L.) Batsch.), is native to arid regions of central Asia. A
      distinguishing feature of P. ferganensis is its prominent, elongated, unbranched
      pattern of leaf venation. To determine whether the long-vein trait could be used
      as a marker in breeding for drought tolerance, we investigated the association
      between this trait and the leaf morphological and physiological parameters
      related to drought response in P. ferganensis, P. persica and two interspecific
      hybrids, one with the long-vein trait (BY94P7585) and one without (BY94P7589).
      The four genotypes were grafted onto "Guardian" peach rootstock and half of the
      plants were assigned to a drought treatment in which irrigation was limited to 25
      50% of the evapotranspiration (ET) rate measured in the remaining well-watered
      plants, which were irrigated to runoff daily. The drought treatment reduced
      photosynthesis and leaf conductance by 49-83% and reduced total leaf area per
      plant by 17-24%, but generally did not affect mid-morning leaf water potential.
      Leaf gas exchange did not differ among genotypes in either treatment. Sorbitol
      accumulated in mature leaves in response to drought, but neither its amount nor
      its metabolism varied systematically with climatic adaptation among genotypes.
      Accumulation of transport sugars was highest in P. ferganensis, indicating that
      growth reduction may represent an important strategy for coping with drought in
      this species. Prunus ferganensis and the hybrids had higher ET than P. persica,
      and seemed to use water opportunistically, maintaining high gas exchange rates
      and consequently high ET when water was available, and avoiding low water
      potentials through stomatal closure as soil water declined. Leaf size (cm(2)
      leaf(-1)) and specific leaf area (cm(2) g(-1) dry mass) were lower in P.
      ferganensis and the hybrids than in P. persica. We conclude that the long-vein
      trait is not a reliable marker for drought tolerance, but leaf traits of P.
      ferganensis such as size and specific leaf area may be useful in P. persica
      breeding programs targeting drought tolerance.

PMID- 12511305
TI  - Variations in transpiration rate and leaf cell turgor maintenance in saplings of
      deciduous broad-leaved tree species common in cool temperate forests in Japan.
AB  - To clarify mechanisms underlying variation in transpiration rate among deciduous
      broad-leaved tree species, we measured diurnal changes in stomatal conductance
      (gs) and leaf water potential, and calculated the maximum transpiration rate
      (Emax), leaf-specific hydraulic conductance (K(s-l)) and difference between the
      soil water potential and the daily minimum leaf water potential (Psis -
      Psi(l,min)). Pressure-volume (P-V) measurements were made on leaves. Saplings of
      eight broad-leaved tree species that are common in Japanese cool temperate
      forests were studied. Maximum transpiration rate varied significantly among
      species. There was a statistically significant difference in Psis - Psi(l,min),
      but not in K(s-l). Species with large Emax also had large Psis - Psi(l,min) and
      gs. The results of the P-V analyses showed that species with a large Psis -
      Psi(l,min) maintained turgor even at low leaf water potentials. The similar daily
      minimum leaf pressure potentials (Psip) across all eight species indicate that
      Psip values below this minimum are critical. Based on these results, we suggest
      that the leaf cell capacity for turgor maintenance strongly affects Psis -
      Psi(l,min) and consequently Emax via stomatal regulation.

PMID- 12511306
TI  - Shoot growth patterns in saplings of Cleyera japonica in relation to light and
      architectural position.
AB  - To gain further insight into crown development, the influences of shoot
      architectural position (branch order) and light environment on patterns of shoot
      growth of Cleyera japonica Thunberg (Theaceae) were investigated. Annual shoot
      length and light environment were positively correlated within same-order
      branches. Shoot length differed significantly among branch orders: shoot length
      was greater for the lower-order branches when light environments were comparable.
      Lower-order branches lengthened to a certain extent even if light availability
      was relatively low, whereas higher-order branches did not grow vigorously even
      when light availability was relatively high. Within same-order branches,
      branching was independent of the light environment of the shoot. Sylleptic shoot
      production differed significantly among branch orders, with most sylleptic shoots
      being produced on second-order branches. It is concluded that both light
      condition and architectural position of shoots must be considered when examining
      the mechanisms underlying crown development.

PMID- 12511307
TI  - Modulations of signal transduction pathways during sepsis and the effects of
      insulin and mifepristone.
AB  - OBJECTIVES: The phosphorylation states and the inferred activation of specific
      members of the mitogen-activated protein kinase (MAPK) pathways (p42/44, p38, and
      SAPK/JNK) were quantitated in the livers of rats by Western blot analysis during
      the progression of sepsis. In addition, the authors examined the effects of
      insulin and mifepristone (RU-486) administration on these signal transduction
      pathways during sepsis. METHODS: Sepsis was brought about by the cecal ligation
      and puncture (CLP) method. The control group underwent sham operation. One
      experimental group was injected with insulin (0.5 U/kg, IV); prior to the CLP or
      sham procedure, the second group was injected with RU-486, a glucocorticoid
      antagonist (mifepristone, 20 mg/kg, IP), and the third group was injected with
      saline (control). RESULTS: The activities of SAPK/JNK were unaltered throughout
      the course of sepsis, while those of p42/44 MAPK increased four-fold after 24
      hours of sepsis. The activation of p38 MAPK was also increased after 0.5 and 1.5
      hours of sepsis, but returned to normal during late sepsis (24 hours). Rats that
      had received RU-486 before CLP showed no change in p42/44 MAPK compared with the
      untreated group, but the drug appeared to suppress the activation after 24 hours
      post-CLP. SAPK/JNK activation, on the other hand, was slightly enhanced by RU-486
      pretreatment after 1.5 and 24 hours of CLP compared with the untreated CLP and
      the treated sham-operated rats. Insulin, given preoperatively, had no effect on
      the activation of SAPK/JNK, although p42/44 MAPK pathways were activated by the
      hormone at 0.5 hours and 1.5 hours post-CLP only, but not in the sham-operated
      controls or at 24 hours post-CLP. The p38 MAPK activation seen after 0.5 and 1.5
      hours of CLP was suppressed by RU-486. Insulin pretreatment appears to suppress
      the phosphorylation of p38 in both the CLP and sham-operated groups. CONCLUSIONS:
      The data suggest that sepsis induces two phases of MAPK activation, an early
      phase in which p38 is active, followed by a second, more pronounced phase of
      p42/44 MAPK activation that occurs only late in sepsis. Hormonal administration
      results suggest that RU-486 suppresses the activation of p38 seen in early
      sepsis, and the activation of p42/44 MAPK seen in late sepsis.

PMID- 12511308
TI  - Left ventricular function after monophasic and biphasic waveform defibrillation:
      the impact of cardiopulmonary resuscitation time on contractile indices.
AB  - Previous work has suggested that low-energy biphasic waveform defibrillation
      (BWD) is followed by less post-resuscitation left ventricular (LV) dysfunction
      when compared with higher-energy monophasic waveform defibrillation (MWD). To the
      best of the authors' knowledge, the effect of cardiopulmonary resuscitation (CPR)
      duration and total ischemia time on LV function after countershock, controlling
      for waveform type, has not been evaluated. OBJECTIVE: To determine the effect of
      CPR duration on LV function after MWD and BWD. METHODS: VF was electrically
      induced in anesthetized and instrumented swine. After 5 minutes of VF, the
      animals were randomized to MWD (n = 22) or one of two BWDs (n = 46). If
      countershock terminated VF but was followed by a nonperfusing rhythm,
      conventional manual CPR without drug therapy was performed until restoration of
      spontaneous circulation (ROSC), defined as a systolic arterial pressure >60 mm Hg
      for 10 minutes without vasopressor support. Systolic LV pressure (LVP), LV dP/dt
      (first derivative of pressure measured over time), and cardiac output (CO) were
      measured at intervals for 60 minutes postresuscitation. CPR times (times to ROSC)
      and hemodynamic variables for the three groups were compared. Multivariable
      linear regression was performed to assess the contribution of defibrillation
      waveform, total joules, and CPR time on LVP, LV dP/dt, and CO at 15, 30, and 60
      minutes postresuscitation. RESULTS: When analyzed as groups, significant
      differences in median number of shocks to terminate VF, total joules, or CPR time
      were not observed between waveform groups. Regression analysis demonstrated that
      increasing CPR time was associated with a significant effect on indices of LV
      function at 15 and 30 minutes postresuscitation. Global LV function was not
      influenced by waveform type or total joules. CONCLUSIONS: Adjustment for CPR
      time, a determinant of total myocardial ischemia time, is necessary when
      defibrillation waveforms are compared for their effect on postresuscitation
      cardiac function and short-term outcome.

PMID- 12511310
TI  - Intramuscular versus oral dexamethasone for the treatment of moderate-to-severe
      croup: a randomized, double-blind trial.
AB  - Glucocorticoids are an effective treatment for croup, although the most
      beneficial route of administration remains unclear. Recent studies have concluded
      that both intramuscular dexamethasone and oral dexamethasone are effective
      treatments, but there are few data directly comparing the two for moderate-to
      severe croup. OBJECTIVES: The authors' primary objective was to determine whether
      there is a difference in proportion of children with resolution of symptoms
      attributable to croup at 24 hours, when treated with oral or intramuscular
      dexamethasone. Secondarily, the authors sought to estimate whether there is a
      difference in proportion of children with resolution of symptoms attributable to
      croup at 10 days and to estimate the interval to complete resolution of symptoms
      between these two routes. METHODS: The authors performed a prospective,
      randomized, double-blind trial involving children aged 3-84 months with moderate
      to-severe croup, presenting to a suburban teaching emergency department (ED).
      Patients were eligible for enrollment if they had inspiratory stridor or a barky
      cough and a croup score of 2 or greater after 10-15 minutes of cool mist therapy.
      The patients were randomized to one of two intervention groups. In both groups,
      the parents were not present in the treatment room during study drug
      administration. One group received 0.6 mg/kg of intramuscular dexamethasone and
      an oral placebo, while the other group received 0.6 mg/kg of oral dexamethasone
      and direct pressure on their thigh with the hub of a syringe. A nurse placed a
      Band-Aid on the site of the real or mock injection. Parents were contacted by
      telephone approximately 1 and 10 days after the index visit to ask about their
      child's symptoms using a standardized questionnaire. Data were analyzed using an
      intention-to-treat approach. RESULTS: Of 126 patients eligible, 96 were
      recruited, with complete follow-up on 95. The groups were similar in all baseline
      characteristics, treatments received in the ED, and disposition. At 24 hours and
      10 days after the visit, there were no statistical differences between the groups
      for the proportion with stridor, expiratory sounds, barky cough, sleep pattern,
      the degree of improvement, or the proportion with complete resolution of symptoms
      at one day. CONCLUSIONS: No statistical differences for any parameters were
      observed between intramuscular and oral dexamethasone treatments for children
      with moderate-to-severe croup at 24 hours or at any time the week after
      treatment. The durations of symptoms were similar between the treatment groups.

PMID- 12511311
TI  - A randomized, clinical trial comparing oral celecoxib 200 mg, celecoxib 400 mg,
      and ibuprofen 600 mg for acute pain.
AB  - OBJECTIVE: Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used to
      treat pain. The objective of this study was to compare the efficacies of
      celecoxib and ibuprofen for the treatment of acute pain. The null hypothesis was
      that no difference between celecoxib and ibuprofen exists. METHODS: The study was
      a prospective, randomized, double-blind, controlled clinical trial. After
      consent, patients rated their pain on a 100-mm visual analog scale (VAS) and
      categorical intensity pain scale. Patients were then randomized to receive 200-mg
      or 400-mg celecoxib or 600-mg ibuprofen (all orally). Patients were contacted 5
      hours after receiving study medication when a second VAS score was recorded,
      along with categorical pain intensity, pain relief score, side effects, and
      number of rescue medications taken. The main outcome measures were change in
      visual analog pain and categorical pain intensity scores, and pain relief scores,
      at five hours. RESULTS: One hundred ten patients were evaluated and 105 were
      enrolled. Thirty-four received celecoxib 200 mg, 32 received celecoxib 400 mg,
      and 39 received ibuprofen 600 mg. Ninety-one were available for the five-hour VAS
      and 88 for the five-hour categorical pain intensity and pain relief analysis: The
      two patients who were unable to read a VAS were excluded, and two enrolled
      patients withdrew prior to medication. One patient was excluded because his
      injury was a fracture, and therefore did not meet the inclusion criteria. There
      was no statistical difference among the treatment groups in age, time from injury
      to medication, initial VAS score, percent lost to follow-up, or treatment with
      adjunctive therapy. There was no statistical difference in change of VAS among
      the groups at five hours: ibuprofen 600 mg (-23.8 mm [95% CI = -31.56 mm to -16.1
      mm] [n = 32]), celecoxib 200 mg (-16.1 mm [95% CI = -24.3 mm to -7.98 mm] [n =
      31]), and celecoxib 400 mg (-12.4 mm [95% CI = -23.1 mm to -1.8 mm] [n = 30]) (p
      = 0.16). There was no significant difference between the groups, at five hours,
      in change of categorical pain intensity (p = 0.11) or pain relief scores (p =
      0.059), though the pain relief scale approached significance favoring ibuprofen.
      CONCLUSIONS: No significant difference exists among emergency department (ED)
      patients treated for acute pain, at five hours, with celecoxib 200 mg, celecoxib
      400 mg, or ibuprofen 600 mg, though the power of the study to detect a change was
      low, 36%. However, the magnitude of pain relief for celecoxib, coupled with the
      cost of the medication, questions its use in the immediate ED setting.

PMID- 12511312
TI  - A randomized, controlled double-blind trial of usual-dose versus high-dose
      albuterol via continuous nebulization in patients with acute bronchospasm.
AB  - OBJECTIVE: Continuous nebulization is becoming more popular in the management of
      acute bronchospasm in the emergency department (ED). Controversy still exists as
      to the optimal dose of albuterol for such exacerbations. The present study
      hypothesis was that there is no difference between continuous nebulization of
      albuterol at 7.5 mg/hr (usual dose) and 15 mg/hr (high dose) in peak flow
      improvement up to three hours. METHODS: This was a randomized, controlled, double
      blind trial, set in an urban county teaching ED. One hundred twenty-seven
      patients with acute bronchospasm and an initial peak flow (PF) less than 75%
      predicted were enrolled. Patients were randomized to usual-dose (UD) or high-dose
      (HD) groups along with a standard treatment protocol. Primary end-points were
      analyzed using repeated-measures analysis of variance (ANOVA), and 95% confidence
      intervals (95% CIs) are given for such variables. RESULTS: Sixty-seven patients
      were randomized to the HD albuterol group, and 63 completed the study. Sixty
      patients were randomized to the UD group, and 55 completed the study. Repeated
      measures ANOVA found no difference in systolic blood pressure, diastolic blood
      pressure, pulse, respiratory rate, Borg dyspnea scale score, and peak flow over
      time between the groups. The mean (+/-SD) peak flow improvement at one hour was
      UD 51 (+/-49) L/min vs. HD 45 (+/-50) L/min, mean difference 6.8 L/min (95% CI = 
      11 to 24.9 L/min). Adjusting for baseline, the percentage increase in peak flow
      at one hour was UD 44% (+/-60%) vs. HD 30% (+/-40%), mean difference 14% (95% CI
      = -4.4% to 32.4%). Time to disposition showed a mean of 188 (+/-129) minutes for
      UD and 230 (+/-183) minutes for HD, mean difference 42 minutes (95% CI = -170 to
      101 min). One patient in the HD group was intubated. Admission rate was UD 70.9%
      vs. HD 65%, mean difference 5.9% (95% CI = -10.9% to 22.7%). CONCLUSIONS: In
      treating acute, moderately-severe bronchospastic ED patients with peak flow less
      than 75% of predicted with albuterol by continuous nebulization, 15 mg/hr appears
      to offer no advantage over 7.5 mg/hr in peak flow improvement or length of stay
      in the ED.

PMID- 12511313
TI  - The status of bedside ultrasonography training in emergency medicine residency
      programs.
AB  - Bedside ultrasonography (BU) is rapidly being incorporated into emergency
      medicine (EM) training programs and clinical practice. In the past decade,
      several organizations in EM have issued position statements on the use of this
      technology. Program training content is currently driven by the recently
      published "Model of the Clinical Practice of Emergency Medicine," which includes
      BU as a necessary skill. OBJECTIVE: The authors sought to determine the current
      status of BU training in EM residency programs. METHODS: A survey was mailed in
      early 2001 to all 122 Accreditation Council for Graduate Medical Education
      (ACGME)-accredited EM residency programs. The survey instrument asked whether BU
      was currently being taught, how much didactic and hands-on training time was
      incorporated into the curriculum, and what specialty representation was present
      in the faculty instructors. In addition, questions concerning the type of tests
      performed, the number considered necessary for competency, the role of BU in
      clinical decision making, and the type of quality assurance program were included
      in the survey. RESULTS: A total of 96 out of 122 surveys were completed (response
      rate of 79%). Ninety-one EM programs (95% of respondents) reported they teach BU,
      either clinically and/or didactically, as part of their formal residency
      curriculum. Eighty-one (89%) respondents reported their residency program or
      primary hospital emergency department (ED) had a dedicated ultrasound machine. BU
      was performed most commonly for the following: the FAST scan (focused abdominal
      sonography for trauma, 79/87%); cardiac examination (for tamponade, pulseless
      electrical activity, etc., 65/71%); transabdominal (for intrauterine pregnancy,
      ectopic pregnancy, etc., 58/64%); and transvaginal (for intrauterine pregnancy,
      ectopic pregnancy, etc., 45/49%). One to ten hours of lecture on BU was provided
      in 43%, and one to ten hours of hands-on clinical instruction was provided in 48%
      of the EM programs. Emergency physicians were identified as the faculty most
      commonly involved in teaching BU to EM residents (86/95%). Sixty-one (69%)
      programs reported that EM faculty and/or residents made clinical decisions and
      patient dispositions based on the ED BU interpretation alone. Fourteen (19%)
      programs reported that no formal quality assurance program was in place.
      CONCLUSIONS: The majority of ACGME-accredited EM residency programs currently
      incorporate BU training as part of their curriculum. The majority of BU
      instruction is done by EM faculty. The most commonly performed BU study is the
      FAST scan. The didactic component and clinical time devoted to BU instruction are
      variable between programs. Further standardization of training requirements
      between programs may promote increasing standardization of BU in future EM
      practice.

PMID- 12511314
TI  - Marijuana use and prior injury among injured problem drinkers.
AB  - OBJECTIVES: The purpose of this paper is to better understand marijuana use among
      injured problem drinkers in the emergency department (ED). The specific
      objectives are: 1) to assess the prevalence of marijuana use; 2) to identify
      factors associated with marijuana use; 3) to determine whether prior injury is
      associated with marijuana use; and 4) to determine whether marijuana-using
      problem drinkers want to change behaviors. METHODS: The authors conducted a post
      hoc analysis on data obtained prospectively. Subjects had injury and problem
      drinking: either measurable alcohol level (blood alcohol concentration, BAC),
      report of drinking, or an Alcohol Use Disorders Identification Test (AUDIT) score
      of > or =8. The study was conducted on weekend nights; 3,776 injured ED patients
      were screened, 383 refused, 578 were enrolled, and 433 had complete data.
      RESULTS: Of the 433 subjects, 48.3% reported using marijuana in the three months
      prior. Marijuana-using problem drinkers had more hazardous drinking, higher AUDIT
      scores (14.0 vs. 11.4, p < 0.001), and higher risk-taking scores (12.4 vs. 10.1,
      p < 0.001). More used other drugs (69.7% vs. 30.3%, p < 0.001). In regression
      analyses, marijuana use remained an independent predictor of prior injury (OR =
      2.16, 95% CI = 1.25 to 3.75), particularly prior alcohol-related (OR = 2.26, 95%
      CI = 1.45 to 3.53) and motor-vehicle-related (OR = 1.69, 95% CI = 1.03 to 2.79)
      injury. Readiness-to-change scores were similar (4.14 vs. 4.22, p = 0.21) between
      users and nonusers. CONCLUSIONS: Marijuana use among injured problem drinkers is
      prevalent. Their risk of prior injury is increased. Counseling for alcohol and
      injury should address marijuana use.

PMID- 12511315
TI  - Predictors of emergency medical services utilization by elders.
AB  - OBJECTIVE: Elders (age > or = 65 years) frequently use emergency medical services
      (EMS) for care. Understanding reasons for EMS use by elders may allow better
      management of EMS demand. To the best of the authors' knowledge, no studies have
      identified patient characteristics associated with EMS use by elders. This study
      aimed to identify patient attributes associated with elder EMS users. METHODS:
      This was a prospective cohort study of non-institutionalized elders presenting to
      an urban university hospital emergency department. Nine hundred thirty elder
      patients completed the survey. The authors asked patients about access to care,
      health beliefs, and reasons for requesting EMS assistance. Univariate and
      logistic regression were used to identify predictors of EMS use. RESULTS: The
      sample had a mean age of 76 years; 37% were male; 79% were African American.
      Thirty percent arrived via EMS. Sixty-five percent of those transported and 46%
      of those not transported by EMS were admitted to the hospital (p < 0.001).
      Reported reasons for using EMS transport included immobility (33%), illness
      (22%), request by others (21%), instruction from health care providers (10%), and
      lack of transportation (10%). Logistic regression identified symptom onset within
      four hours of seeking care (OR = 3.1), age > or = 85 years (OR = 1.63), increased
      deficiencies in activities of daily living (OR = 1.40 per deficiency), worse
      physical functioning (OR = 1.14/10 points), and worse social functioning (OR =
      1.06/10 points) as factors associated with EMS use. CONCLUSIONS: Elders report
      using EMS because of immobility, perceived medical needs, or requests by others.
      Similarly, the presence of acute illness symptoms, older age, and poor social and
      physical function, rather than health beliefs, predict EMS use among elders.
      These factors must be considered when managing the demand for EMS services.

PMID- 12511316
TI  - Some thoughts regarding gender issues in the mentoring of future academicians.

PMID- 12511318
TI  - Need for brief interventions for marijuana and alcohol use related to injuries.

PMID- 12511319
TI  - Ethics seminars: health care proxies and suicidal patients.
AB  - Advance directives, health care proxies, and living wills are forms of advance
      planning that permit patients to make decisions regarding their health care and
      are used when the patient becomes incapacitated. The ethics of allowing these
      forms of advance planning are questioned when the patient has attempted suicide.
      The authors present an ethical analysis of a case of an elder patient who
      overdosed on sustained-release diltiazem and had a health care proxy who wanted
      all treatments stopped.

PMID- 12511320
TI  - Patient safety: a curriculum for teaching patient safety in emergency medicine.
AB  - The last decade has witnessed a growing awareness of medical error and the
      inadequacies of our health care delivery systems. The Harvard Practice Study and
      subsequent Institute of Medicine Reports brought national attention to long
      overlooked problems with health care quality and patient safety. The Committee on
      Quality of Health Care in America challenged professional societies to develop
      curriculums on patient safety and adopt patient safety teaching into their
      training and certification requirements. The Patient Safety Task Force of the
      Society for Academic Emergency Medicine (SAEM) was charged with that mission. The
      curriculum presented here offers an approach to teaching patient safety in
      emergency medicine.

PMID- 12511321
TI  - Emergency department services for patients with alcohol problems: research
      directions.
AB  - This report summarizes recommendations on research directions developed from the
      conference "Alcohol Problems among Emergency Department Patients: Research on
      Identification and Intervention." The conference was developed in order to
      evaluate the existing state of the art research on emergency department
      interventions for alcohol problems, and offer further recommendations for
      research.

PMID- 12511322
TI  - Does soccer headgear attenuate the impact when heading a soccer ball?
AB  - There is increasing concern that repetitive blows to the head, such as those from
      heading a soccer ball, can cause measurable cognitive impairment. Reducing
      acceleration of impact could reduce neurologic sequelae. OBJECTIVE: To measure
      the effectiveness of four different types of soccer headgear in reducing the
      acceleration of impact. METHODS: A standard magnesium headform was instrumented
      with a triaxial accelerometer. A soccer ball was propelled at the headform at
      three different speeds known to occur in soccer play: 9, 12, and 15 m/sec (20,
      26, and 34 mph). The main outcome was the peak acceleration of the headform
      associated with these impacts with and without protective headgear. RESULTS: Peak
      accelerations were found in a range from 144 m/s(2) to 289 m/s(2) (14.67-29.5 G,
      G = 9.81 m/s(2)). Using multivariate analysis of variance (MANOVA) methods to
      compare the headbands and controls, there was no significant difference in the
      measured accelerations at the center of gravity with or without headgear (p =
      0.50). However, the interaction term of headbands, pressure, and speed was
      significant at F = 5.51 and p = 0.00001. Using contrasts within conditions, some
      headbands were found to cause a decrease in peak acceleration at the highest
      speed and pressure. CONCLUSIONS: Currently available headgear for soccer heading
      shows little ability to attenuate impact during simulated soccer heading.
      However, statistically significant decreases are present at the highest speeds
      and pressures tested, suggesting the headbands may play a role in decreasing
      impact for more forceful blows.

PMID- 12511323
TI  - Emergency bedside ultrasound to detect pneumothorax.
AB  - A relatively new application of emergency ultrasound is its use in the diagnosis
      of pneumothorax. In patients with major trauma, early detection and treatment of
      pneumothorax are vital. Chest radiography in these patients is limited to
      anteroposterior (AP) supine films, in which radiographic features of pneumothorax
      may be quite subtle. Hence, rapid and accurate bedside ultrasonography can
      expedite resuscitation. Sonographic features of pneumothorax have been identified
      in a number of studies. The technique involves identification of the pleural line
      and observation for features such as "lung sliding" and comet-tail artifacts,
      which are absent in pneumothorax. Based on a review of the literature, the author
      describes these features and discusses the utility of emergency ultrasound in
      detecting pneumothorax.

PMID- 12511324
TI  - Unsupported "Efficacy" claims of gamma hydroxybutyrate (GHB).

PMID- 12511325
TI  - A novel approach to resident evaluation and the core competencies.

PMID- 12511327
TI  - Evidence-based recommendations for neovascular glaucoma.

PMID- 12511329
TI  - Evidence-based recommendations for neovascular glaucoma.

PMID- 12511330
TI  - Complications of lacrimal plug implantation.

PMID- 12511331
TI  - Complications of lacrimal plug implantation.

PMID- 12511334
TI  - Brimonidine and latanoprost as adjunctive therapy.

PMID- 12511337
TI  - NTG history.

PMID- 12511338
TI  - Three tough acts to follow and the watch changes. Now, what?

PMID- 12511339
TI  - Do you speak ocular tumor?

PMID- 12511340
TI  - Indocyanine green angiography in chorioretinal diseases: indications and
      interpretation: an evidence-based update.
AB  - TOPIC/PURPOSE: To assess the clinical usefulness and relevance of indocyanine
      green angiography (ICG) in the investigation of chorioretinal disorders and
      assess specifically in what conditions it may add useful information to that
      obtained using standard fluorescein angiography. CLINICAL RELEVANCE: Many
      publications on ICG have appeared in recent years touting its use in
      ophthalmology. These publications have led to increasing use of this technique
      and to its application in numerous retinal diseases in which the fluorescein
      angiographic findings have been thoroughly described. METHODS/LITERATURE
      REVIEWED: During this systematic literature review, we identified and reviewed a
      total of 376 articles, from among which we selected 92 that we considered most
      relevant to our purpose of evaluating published evidence as to the efficacy of
      ICG. We excluded many articles with weak study designs and those that simply
      duplicated previously published information. Our literature search used PubMed
      and was confined to articles in English or that included an English abstract.
      RESULTS: Our systematic review suggests that ICG has relatively few specific
      indications for use as justified by previously published peer-reviewed studies.
      In keeping with the requirements for this Journal's evidence-based articles, we
      have divided our clinical recommendations for the use of ICG into three
      categories: (A) strongly recommended and supported by strong evidence; (B)
      recommended with moderately strong supporting evidence; (C) not recommended at
      present because supported only by anecdotal or group consensus evidence. We
      highly recommended ICG for (1) identification of polypoidal choroidal
      vasculopathy, (2) occult choroidal neovascularization, (3) neovascularization
      associated with pigment epithelial detachments, and (4) recurrent choroidal
      neovascular membranes. These are all conditions in which ICG contributes to the
      identification of lesions that may be treatable. We recommend ICG with some
      enthusiasm for identifying feeder vessels in age-related macular degeneration,
      choroidal neovascular membranes, chronic central serous retinopathy, multiple
      evanescent white dot syndrome, vasculitis, acute multifocal placoid pigment
      epitheliopathy, Vogt-Koyanagi-Harada syndrome, macular lesions associated with
      angioid streaks, and birdshot retinopathy. In all these conditions, ICG may help
      establish a diagnosis and provide some useful guidance for therapy. At present,
      we do not recommend ICG for scleritis and posterior scleritis, drusen
      differentiation, Behcet's disease, or sarcoidosis, because it has not been
      demonstrated to add useful clinical information. CONCLUSIONS: ICG, although now a
      well established technique, has clear advantage over fluorescein angiography in
      relatively few chorioretinal disorders. It has, however, contributed to the
      understanding of pathologic processes in many ocular diseases. As yet, no
      published randomized controlled clinical trials show any benefit to the use of
      ICG in the management of any specific ocular disease.

PMID- 12511342
TI  - Early age-related maculopathy in the cardiovascular health study.
AB  - OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and
      its relation to atherosclerosis, lipids, hypertension, and inflammatory factors
      in a population studied for cardiovascular disease risk factors and outcomes.
      DESIGN: Population-based cohort study. PARTICIPANTS: A biracial population of
      2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living
      in four US counties (Allegheny County, Pennsylvania; Forsyth County, North
      Carolina; Sacramento County, California; and Washington County, Maryland) were
      examined during the interval from 1997 to 1998. METHODS: Drusen and other lesions
      typical of ARM were identified by examining a 45 degrees color fundus photograph
      of one eye of each participant and classified by means of a modification of the
      Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Early
      ARM. RESULTS: Early ARM was present in 15.5% and late ARM in 1.3% of the cohort.
      The overall prevalence of any ARM was lower in blacks (9.1%) compared with whites
      (18.2%). While controlling for age, race, gender, and total calories consumed in
      the diet, factors associated with ARM were cerebral white matter disease as
      detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95% confidence
      interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per
      10 mg/dl increase 0.95; 95% CI, 0.91, 0.98, P = 0.02). There were no associations
      between hypertension, blood pressure, common carotid artery plaque, or any
      systemic inflammatory factors studied and early ARM. CONCLUSIONS: This population
      based study documents the higher prevalence of ARM in whites compared with
      blacks. Although an association was found between signs of white matter disease
      and early ARM, there was no evidence of an association of ARM with either
      hypertension or inflammatory factors.

PMID- 12511343
TI  - Five-year cumulative incidence and progression of epiretinal membranes: the Blue
      Mountains Eye Study.
AB  - PURPOSE: To describe the 5-year cumulative incidence and change in epiretinal
      membranes in a defined older Australian population. DESIGN: Population-based
      cohort study. PARTICIPANTS: Three thousand six hundred fifty-four persons 49
      years of age or older, living in the Blue Mountains area, west of Sydney,
      Australia, participated in the baseline survey during 1992 to 1994. The cohort
      was reexamined after 5 years in 1997 to 1999. Excluding persons (543) who died
      since the baseline, 75% of survivors (n = 2335) attended the follow-up
      examination. METHODS: All participants underwent a detailed eye examination,
      including stereo retinal photography. Epiretinal membranes were diagnosed from
      grading of baseline and 5-year retinal photographs. MAIN OUTCOME MEASURES:
      Epiretinal membranes were classified as either preretinal macular fibrosis (PMF),
      with retinal folds, or as a less severe form, termed cellophane macular reflex
      (CMR), without retinal folds. The incidence of epiretinal membranes was
      determined if either lesion was found in eyes with no preexisting epiretinal
      membrane at baseline. Progression was defined if the area of involvement
      increased by more than 25%, regression if it decreased by more than 25%, and
      stable if it changed by less than 25%. RESULTS: Epiretinal membranes developed in
      the first eye of 108 of 2030 participants who had no sign of this condition in
      either eye at baseline, 5.3%, 95% confidence interval (CI) 4.4 to 6.4. Five-year
      cumulative incidence rates for PMF and CMR were 1.5% and 3.8%, respectively. Of
      those participants with epiretinal membranes in one eye at baseline, 18 of 133
      (13.5%) developed this sign in their second eye after 5 years. New epiretinal
      membranes (mostly CMR) occurred in 15 of 165 subjects (9.1%; CI, 5.2-14.6) who
      had undergone cataract surgery since the Blue Mountains Eye Study I. This rate
      was significantly higher than in the nonsurgical group, 92 of 1861 (4.9%; CI, 4.0
      6.0) of whom developed epiretinal membranes. Progression from CMR to PMF was
      observed in 17 of 183 eyes (9.3%). Existing epiretinal membranes progressed,
      regressed, or remained stable in 28.6%, 25.7%, and 38.8% of eyes, respectively.
      CONCLUSIONS: This study has documented the 5-year cumulative incidence and the
      natural history of epiretinal membranes in an older population.

PMID- 12511344
TI  - Five-year change in visual acuity and incidence of visual impairment: the Blue
      Mountains Eye Study.
AB  - PURPOSE: To describe the 5-year change in visual acuity and the incidence of
      visual impairment in a population-based cohort. DESIGN: Population-based
      epidemiologic study. PARTICIPANTS: Of the 3654 participants of the Blue Mountains
      Eye Study (BMES I) baseline examination (aged 49 years+ during 1992-1994), 2335
      were reexamined during the 5-year follow-up examinations from 1997 to 1999 (BMES
      II), and 543 persons had died since BMES I. METHODS: Visual acuity was measured
      using a logarithm of the minimum angle of resolution chart in both eyes
      separately before and after standardized refraction. Pupils were dilated and a
      detailed examination was performed. MAIN OUTCOME MEASURES: Visual impairment,
      after best refractive correction, was defined as any (visual acuity </=20/40;
      </=41 letters) and severe (visual acuity </=20/200; 0-5 letters) in keeping with
      the Beaver Dam Eye Study. Incident binocular visual impairment was defined as
      visual acuity </=20/40 in both eyes at follow-up, where visual acuity was >20/40
      in both eyes at baseline. Incident binocular severe visual impairment was defined
      as visual acuity </=20/200 in both eyes at follow-up, where visual acuity was
      >20/200 in both eyes at baseline. The incidence for three other levels of visual
      impairment is also given: <20/40, <20/70, and <20/200. Monocular visual
      impairment was defined as impairment in one eye only at follow-up, where both
      eyes were unimpaired at baseline. Incident doubling and halving of the visual
      angle were calculated. RESULTS: Incidence rates for visual impairment increased
      significantly with age. Any incident impairment </=20/40 occurred binocularly in
      41 persons (1.9%) and monocularly in 150 persons (7.1%). Severe incident
      impairment </=20/200 occurred binocularly in 3 persons (0.1%) and monocularly in
      44 persons (2.1%). Incident impairment <20/40 occurred binocularly in 37 persons
      (1.7%) and monocularly in 134 persons (6.3%). Impairment <20/70 occurred
      binocularly in 15 persons (0.7%) and monocularly in 84 persons (3.8%). Impairment
      <20/200 occurred binocularly in 3 persons (0.1%) and monocularly in 44 persons
      (1.9%). Women consistently had a higher incidence of visual impairment than men,
      although this was often not statistically significant after adjusting for age.
      Increasing age was a strong predictor of visual impairment. CONCLUSIONS: This
      study has documented the 5-year incidence and causes of visual impairment in an
      older Australian population.

PMID- 12511345
TI  - Influence of short-term antioxidant supplementation on macular function in age
      related maculopathy: a pilot study including electrophysiologic assessment.
AB  - PURPOSE: To evaluate the influence of short-term antioxidant supplementation on
      retinal function in age-related maculopathy (ARM) patients by recording focal
      electroretinograms (FERGs). DESIGN: Nonrandomized, comparative clinical trial.
      PARTICIPANTS: Thirty patients with early ARM and visual acuity >/=20/30, divided
      into two groups, similar for age and disease severity: antioxidant group (ARM-A,
      n = 17) and no treatment group (ARM-NT, n = 13). Eight age-matched normal
      subjects divided into antioxidant (N-A, n = 4) or no treatment (N-NT, n = 4)
      groups. METHODS: ARM-A patients and N-A patients had oral supplementation of
      lutein, 15 mg; vitamin E, 20 mg; and nicotinamide, 18 mg, daily for 180 days,
      whereas ARM-NT patients and N-NT patients had no dietary supplementation during
      the same period. Eight of the 17 ARM-A patients took supplementation for an
      additional 180-day period. In all patients and normal subjects, FERG assessment
      was performed at the study entry (baseline) and after 180 days. Further testing
      was performed at 360 days for the eight ARM-A patients taking supplements and for
      one ARM-A patient who had discontinued supplementation after 180 days. FERGs were
      recorded in response to a 41-Hz sinusoidally modulated uniform field (93.5%
      modulation depth) presented to the macular region (18 degrees ) on a light
      adapting background. In a subgroup of patients (11 ARM-A and 5 ARM-NT), whose
      responses had suitable signal-to-noise ratios, FERGs were also recorded at
      different stimulus modulation depths between 8.25% and 93.5%. MAIN OUTCOME AND
      MEASURES: Amplitude (in micro V) and phase (in degrees) of the FERG fundamental
      harmonic component. FERG modulation thresholds, estimated from the value of log
      modulation depth yielding a criterion response. RESULTS: At 180 days, FERGs of
      ARM-A patients and N-A patients were increased in amplitude (mean change, 0.11
      and 0.15 log micro V, respectively, P </= 0.01) compared with baseline values,
      whereas no significant changes in FERG amplitudes of ARM-NT patients and N-NT
      patients were found (mean change, -0.004 and -0.023 log micro V, respectively).
      In all groups no changes in the FERG phase were found. FERG modulation thresholds
      decreased with respect to baseline values (mean change, -0.36 log units, P <
      0.01) in ARM-A patients, whereas no significant change (mean change, 0.07 log
      units) in ARM-NT patients was seen. At 360 days, FERGs of ARM-A patients taking
      supplementation were still increased in amplitude with respect to baseline (P <
      0.05) but did not differ from those recorded at 180 days. In the patient who had
      discontinued supplementation, FERG amplitude decreased from the 180 days value,
      approaching that recorded at baseline. CONCLUSIONS: Although this study provides
      no evidence for the long-term benefit of antioxidants in ARM, the results suggest
      that increasing the level of retinal antioxidants might influence macular
      function early in the disease process, as well as in normal aging.

PMID- 12511347
TI  - Macular pucker removal with and without internal limiting membrane peeling: pilot
      study.
AB  - OBJECTIVE: To investigate results of macular pucker surgery with and without
      internal limiting membrane (ILM) peeling. DESIGN: Retrospective noncomparative
      interventional case series. PARTICIPANTS: Forty-four consecutive patients
      underwent pars plana vitrectomy to remove an idiopathic macular pucker by two
      surgeons from June 1999 to July 2000. INTERVENTION: During the vitrectomy, one
      surgeon removed only the macular epiretinal membrane (24 patients), whereas the
      other surgeon removed the macular epiretinal membrane and then performed an
      additional ILM peeling (20 patients). MAIN OUTCOME MEASURES: Visual acuity and
      recurrence of macular pucker. RESULTS: Twenty-four (55%) patients underwent pars
      plana vitrectomy without ILM peeling, and 20 patients (45%) underwent pars plana
      vitrectomy with ILM peeling. Visual acuity improved or was unchanged in 79% of
      operated eyes without ILM peeling and 100% of operated eyes with ILM peeling (P =
      0.01). Visual acuity improved 5 or more lines in 25% of operated eyes without ILM
      peeling and 30% of operated eyes with ILM peeling. At the final visit, 21% of
      eyes without ILM peeling at the initial surgery showed postoperative recurrent
      macular pucker or persistent contraction to the ILM, whereas none of the eyes
      with ILM peeling had evidence of this. CONCLUSIONS: This pilot study provides
      evidence that peeling of the ILM during macular pucker surgery may not have
      deleterious effects.

PMID- 12511348
TI  - Scotoma size and reading speed in patients with subfoveal occult choroidal
      neovascularization in age-related macular degeneration.
AB  - PURPOSE: To investigate the correlation between reading speed and scotoma size in
      patients with subfoveal occult with no classic choroidal neovascularization (CNV)
      in age-related macular degeneration (AMD) participating at 2 of 28 centers in the
      Verteporfin in Photodynamic Therapy trial. DESIGN: Prospective, observational
      case series. PARTICIPANTS: Twenty-two eyes of 22 patients with occult with no
      classic CNV in AMD. METHODS: Patients' reading speed was examined using a German
      language reading test (Radner Lesetest). Scotoma size was measured using the
      microperimetry program 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. MAIN
      OUTCOME MEASURES: Reading acuity, reading speed, size of absolute (AS) and
      relative scotoma (RS). RESULTS: There was a significant correlation between the
      size of AS and reading speed (r = -0.48, P = 0.023), as well as AS and reading
      acuity (r = 0.52, P = 0.013). No correlation was seen between RS and reading
      speed or reading capacity. CONCLUSION: The size of absolute scotoma correlated
      significantly with reading capacity and reading speed and may influence these
      measures.

PMID- 12511349
TI  - Posterior chorioretinal atrophy and vitreous phenotype in a family with Stickler
      syndrome from a mutation in the COL2A1 gene.
AB  - PURPOSE: To report posterior chorioretinal atrophy (PCRA) and correlate the
      vitreous phenotype with inheritance of the disease mutation in a family with
      vitreoretinal dystrophy. DESIGN: Prospective observational case series. METHODS:
      Twenty-four members of a family with 14 affected individuals were examined, and
      genetic linkage analysis was performed at the COL2A1, COL11A1, and Wagner disease
      loci. The vitreous phenotype was prospectively graded as optically empty with
      retrolenticular membrane, fibrillar, or normal. Ocular ultrasonography and
      optical coherence tomography (OCT) were performed on selected individuals to
      study the vitreous structure and vitreoretinal interface. RESULTS: The 6-year-old
      proband had PCRA and optically empty vitreous without systemic features,
      suggestive of Wagner disease. The family history was negative for systemic
      disease, except for one cousin with cleft palate. However, when examined,
      clinical features of the 14 affected subjects included 5 with small chin, 4 with
      at least submucosal cleft palate, and 9 with a myopic refractive error greater
      than 5 diopters. Lens opacity or previous cataract extraction was found in 13
      family members. All affected individuals in whom the vitreous could be examined
      had an optically empty vitreous with retrolental membrane. Posterior
      chorioretinal atrophy was found in eight of the affected subjects. The finding
      was not limited to highly myopic subjects, nor did all the high myopes have PCRA.
      Ultrasonography and OCT revealed vitreous adherent to the retina, but without
      apparent retinal distortion or edema of the macula. Significant linkage was
      established to the COL2A1 locus; the other loci were excluded. A single
      nucleotide insertion mutation (c.2012 2013insC) was identified in exon 34,
      leading to a downstream premature stop codon in the COL2A1 gene. CONCLUSIONS:
      Although posterior chorioretinal atrophy and vitreoretinal degeneration have been
      classically associated with Wagner disease, we demonstrate its presence in a
      family with typical Stickler syndrome. On the basis of clinical,
      ultrasonographic, and OCT studies, the etiology of PCRA in this family does not
      seem to be attributable to vitreomacular traction or myopia. The vitreous
      findings in this large family confirm reports that mutations in the COL2A1 gene
      lead to the optically empty vitreous with retrolenticular membrane phenotype.

PMID- 12511350
TI  - Comparison of external dacryocystorhinostomy with nonlaser endonasal
      dacryocystorhinostomy.
AB  - OBJECTIVE: We compared outcomes after dacryocystorhinostomies (DCRs) performed by
      the traditional external approach (EX-DCR) or by a nonlaser, nonendoscopic
      endonasal approach (EN-DCR). DESIGN: Retrospective, nonrandomized, comparative
      interventional case series. PARTICIPANTS: A total of 354 consecutive cases of DCR
      were reviewed in 349 patients performed by one surgeon over a 4-year period with
      a minimum 1 year of follow-up using either EX-DCR or EN-DCR. Only patients with
      primary nasolacrimal duct obstruction and no eyelid, lacrimal sac, or canalicular
      pathology were included. INTERVENTION: A total of 153 EX-DCR and 201 EN-DCR
      patients were identified. EX-DCR was performed under sterile conditions, and EN
      DCR was performed with a clean setup. Silicone stents were placed for 3 months.
      MAIN OUTCOME MEASURES: Patency of the lacrimal system as assessed by history and
      irrigation. Outcomes were graded as full success, partial success, or failure.
      Operative durations and postoperative complications were recorded from hospital
      charts. RESULTS: There was no significant difference in age or gender
      distribution between the two groups. The mean operative duration was 34.3 minutes
      for EX-DCR and 18.5 minutes for EN-DCR (P < 0.0001, t test). Full success was
      achieved in 90.2% of EX-DCRs and 89.1% of EN-DCRs. Partial success was recorded
      in 2.0% of EX-DCRs and 4.0% of EN-DCRs. The failure rate was 7.8% for EX-DCR and
      7.0% for EN-DCR. There was no statistical significance between these outcomes
      with a two-sample test for equality of proportions with continuity correction (P
      = 0.914, power = 80% for alpha = 0.05 to detect a decreased success rate of 12%).
      Eleven of the failed cases in each group underwent revision EN-DCR surgery, with
      90.9% success in each group. Epistaxis requiring perioperative nasal packing
      occurred in 7 (4.6%) EX-DCR patients and 11 (5.5%) EN-DCR patients. Wound
      complications in EX-DCR included bruising in four patients, localized infections
      in two patients, and punctal eversion in six patients. In EN-DCR, inadvertent
      incision of the periorbita occurred in five patients. One patient reported
      transient diplopia after the medial rectus was inadvertently pulled during an EN
      DCR. Five patients had an EX-DCR on one side and an EN-DCR on the other side. All
      five reported retrospectively that they preferred the endonasal approach.
      CONCLUSIONS: The EN-DCR approach is more rapid than the traditional external
      approach, has an equivalent surgical success rate, and was preferred by patients
      who had alternative techniques performed on opposite sides.

PMID- 12511351
TI  - Loss of tear duct-associated lymphoid tissue in association with the scarring of
      symptomatic dacryostenosis.
AB  - OBJECTIVE: To determine whether organized mucosa-associated lymphoid tissue
      (MALT) is a normal component of the human efferent tear ducts or is acquired in
      reaction to chronic inflammation. DESIGN: Nonrandomized comparative (cadaver
      controlled) study with histopathologic correlations. MATERIALS: Tissue specimens
      from nasolacrimal ducts of 38 patients undergoing endonasal dacryocystorhinostomy
      in postinflammatory dacryostenosis with signs of chronic inflammation were
      analyzed using histologic examination and immunohistochemical studies. Only
      tissue specimens revealing proliferative sclerotic forms of chronic fibrosis were
      chosen for the study. Eighty specimens from the lacrimal systems of body donors
      served as controls. TESTING: Tissue specimens from each lacrimal system were
      prepared and processed with paraffin, sectioned, stained using different
      histologic methods with an array of specific antibodies, and examined by light
      microscopy. MAIN OUTCOME PARAMETERS: The distribution of intraepithelial and
      subepithelial defense cells was analyzed to identify plasma cells, secretory
      immunoglobulins, lymphocytes, dendritic cells, and organized mucosa-associated
      lymphoid tissue. RESULTS: The presence of secretory immunoglobulin A was
      demonstrated in subepithelial plasma cells and in the cytoplasm of apical
      epithelial cells in both chronically inflamed and healthy lacrimal systems. In
      more than one third of cases from body donors, but in only a few biopsy specimens
      from patients, organized lymphoid tissue was found with the cytomorphologic and
      immunophenotypical features of MALT. All other cases showed a diffuse infiltrate
      of defense cells within the lamina propria. CONCLUSIONS: The development of tear
      duct-associated lymphoid tissue (TALT) is a common feature that is often found in
      symptomatically normal nasolacrimal ducts. Because TALT seems to be lost
      associated with the scarring of symptomatic dacryostenosis, it is unlikely that
      the presence per se of TALT leads to scarring. Future studies are needed to
      explain the development of TALT.

PMID- 12511352
TI  - Amniotic membrane transplantation for reconstruction of the conjunctival
      fornices.
AB  - PURPOSE: To describe the clinical outcome of amniotic membrane transplantation
      (AMT) for fornix reconstruction in a variety of ocular surface disorders. DESIGN:
      Noncomparative interventional case series. PARTICIPANTS: Seventeen eyes in 15
      patients with symblepharon. Four eyes had ocular-cicatricial pemphigoid, two eyes
      had symblepharon after pterygium excision, four eyes had chemical or mechanical
      trauma, two eyes had strabismus surgery, two eyes (one patient) had Stevens
      Johnson syndrome, one eye had toxic epidermal necrolysis, and two eyes (one
      patient) had chronic allergic conjunctivitis. INTERVENTION: The subconjunctival
      scar tissue was dissected from the episclera, and the freed conjunctival flap was
      recessed to the fornix. A layer of amniotic membrane (AM) was applied to cover
      the exposed episclera. The fornical edge of the membrane was anchored with
      sutures passing through the full thickness of the lid. MAIN OUTCOME MEASURES: A
      deep conjunctival fornix, lack of motility restriction. RESULTS: The mean follow
      up period was 37 +/- 24 months (range, 9-84 months). Complete fornix
      reconstruction was demonstrated in 12 of 17 eyes (70.6%), whereas 2 eyes had a
      partial success, and 3 eyes (3 patients) had recurrence of symblepharon with
      restricted motility. In eyes that demonstrated partial success or failure, the
      underlying etiology was either an autoimmune disorder or a recurrent pterygium.
      The most successful outcome was observed in eyes with symblepharon associated
      with trauma. CONCLUSIONS: AMT is an effective method of fornix reconstruction for
      the repair of symblepharon in a variety of ocular surface disorders. Future
      modifications, including an epithelial cellular component on the AM (conjunctival
      autograft or ex vivo expanded epithelial stem cells) may improve the outcome of
      this surgical procedure.

PMID- 12511353
TI  - Pleomorphic lipoma of the orbit: a case series and review of literature.
AB  - OBJECTIVE: Pleomorphic lipomas are rare benign tumors that can resemble a variety
      of malignant soft tissue tumors on histologic examination. Six cases of patients
      with orbital pleomorphic lipoma, one of which was proven to be bilateral, are
      presented. DESIGN: Retrospective, noncomparative, interventional case series with
      clinicopathologic correlation. METHODS: Clinical and histologic review of 6
      patients with pleomorphic lipomas of the orbit and histologic review of fat from
      22 exenteration specimens and 20 other orbital procedures. MAIN OUTCOME MEASURES:
      Evidence of histologic abnormalities in histologic specimens. RESULTS:
      Pleomorphic spindle cells and multinucleated cells with nuclei arranged in a
      floret-like pattern were present in 7 specimens from 6 patients presenting with a
      clinical diagnosis of orbital fat prolapse, but there were no similar cell types
      present in the adipose tissue of 22 exenteration or 20 other orbital specimens.
      CONCLUSION: Pleomorphic lipoma may arise in the orbit, presenting as what was
      hitherto considered to be age-related epibulbar prolapse of orbital fat.

PMID- 12511354
TI  - Pupil light reflex in normal and diseased eyes: diagnosis of visual dysfunction
      using waveform partitioning.
AB  - OBJECTIVE: To evaluate changes in pupil size (corresponding to neuronal firing)
      within different time windows of the pupil light reflex in patients and normal
      subjects to understand which segments of the pupil waveform are best able to
      differentiate normal from abnormal subjects. DESIGN: Comparative, observational
      case series. PARTICIPANTS: Forty-nine normal subjects and 25 patients with known
      unilateral or asymmetric visual field damage were tested. METHODS: A dual-channel
      infrared pupillograph was used to simultaneously record the right and left pupil
      diameters at a rate of 60 Hz. Each eye was stimulated alternately (30 degrees
      full-field, 200 milliseconds duration every 3 seconds) over 10 different stimulus
      intensities. The recorded waveform of the pupil light reflex was subdivided into
      six time windows based on landmarks corresponding to contraction onset, maximum
      contraction velocity, peak contraction, and maximum dilation velocity to assess
      which portion was most affected by disease. MAIN OUTCOME MEASURES: The linear
      correlation between pupil contractions elicited by right versus left full-field
      stimulation at different light intensities provided diagnostic parameters (slope,
      intercept, and correlation coefficient R(2)) that were useful for differentiating
      normal subjects from patients and for categorizing disease. Sensitivity and
      specificity of the time windows were evaluated with receiver-operator curve
      analysis. RESULTS: The diagnosis of asymmetric disease was greatest at time
      windows that included pupil contraction but not dilation. When the contraction
      phase was subdivided into an early phase and into a late phase, the late phase
      was the most diagnostic compared with the entire phase of contraction amplitude
      (onset to peak contraction). CONCLUSIONS: By use of a range of light intensity,
      the change in pupil size measured between the time at which maximum contraction
      velocity occurs and the time to peak contraction provided the best response
      parameter for objective diagnosis of asymmetric disease of the anterior visual
      pathway. The waveform of the pupil light reflex may be an expression of the
      firing of retinal ganglion cells. Therefore, understanding which segment of the
      pupil light reflex provides maximal diagnostic power may give insight into how
      disease affects the pattern of neuronal firing rate.

PMID- 12511355
TI  - Ophthalmologic involvement in the syndrome of headache, neurologic deficits, and
      cerebrospinal fluid lymphocytosis.
AB  - PURPOSE: To emphasize that papilledema and other ophthalmic manifestations may
      occur in the syndrome of headache, neurologic deficits, and cerebrospinal fluid
      lymphocytosis (HaNDL). DESIGN: Two interventional case reports. METHODS: Two
      patients were seen with ophthalmologic findings, including decreased vision,
      papilledema, sixth nerve palsy, and a variety of neurologic deficits. Each
      underwent cerebrospinal fluid analysis and intracranial pressure measurement by
      spinal tap and neuroimaging studies to confirm the diagnosis of HaNDL. RESULTS:
      Both patients received acetazolamide to lower intracranial pressure. The first
      patient had complete resolution of signs and symptoms. The second, who was also
      given systemic corticosteroids, was left with diminished visual acuity in the
      right eye with nasal visual field loss and optic atrophy. CONCLUSIONS: The
      diagnosis of HaNDL is one of exclusion, which must be made in conjunction with a
      neurologist. HaNDL may be accompanied by elevated intracranial pressure and
      papilledema. As in other disorders causing papilledema, these patients may have
      permanent visual sequelae. Recognition by the ophthalmologist of this rarely
      reported syndrome will facilitate prompt patient diagnosis and treatment.

PMID- 12511356
TI  - Amniotic membrane transplantation with conjunctival autograft for recurrent
      pterygium.
AB  - OBJECTIVE: To study the effect of amniotic membrane transplantation (AMT)
      combined with either limbal autograft transplantation (LAT) or conjunctival
      autograft transplantation (CAT) in recurrent pterygium. DESIGN: Retrospective,
      noncomparative, interventional case series. PARTICIPANTS: Twenty-seven eyes of 27
      patients with recurrent pterygium. The mean number of prior surgeries was 3.1
      (range, 1-10). Fifteen eyes each had restriction of ocular movement and
      symblepharon before surgery. INTERVENTION: Patients were treated by AMT with
      either LAT (n = 15) or CAT (n = 12). MAIN OUTCOME MEASURES: Recurrence of
      pterygium, improvement in ocular movement, and symblepharon formation. RESULTS:
      Twenty-three (85.2%) of 27 eyes showed no recurrence with a mean observation
      period of 67.0 weeks. Fourteen eyes (93.3%) each showed improvement in ocular
      movement restriction and symblepharon after AMT. In four eyes that developed
      recurrence, three had LAT and one had CAT combined with AMT, suggesting that
      there was no difference in surgical outcome between LAT and CAT. CONCLUSIONS: AMT
      with CAT is a safe and effective method for recurrent pterygium, especially that
      associated with ocular movement restriction and symblepharon. Considering the
      potential adverse effects associated with limbal excision, AMT plus CAT may be
      preferred over AMT plus LAT.

PMID- 12511357
TI  - Management of aniridic keratopathy with keratolimbal allograft: a limbal stem
      cell transplantation technique.
AB  - OBJECTIVE: Aniridic keratopathy is a major cause of vision loss in patients with
      aniridia. Penetrating keratoplasty has been proven ineffective for the long-term
      treatment of this disorder because it does not address the stem cell deficiency
      that is the primary etiologic factor. We evaluated the role of keratolimbal
      allograft (KLAL), a stem cell transplantation technique, for the treatment of
      patients with aniridic keratopathy. DESIGN: Retrospective noncomparative
      interventional case series. PARTICIPANTS: Thirty-one eyes of 23 patients with
      aniridic keratopathy. INTERVENTION: KLAL. MAIN OUTCOME MEASURES: Ocular surface
      stability, visual acuity, and success of subsequent penetrating or lamellar
      keratoplasty. RESULTS: Thirty-one eyes of 23 patients were treated with KLAL and
      followed up for 12 to 117 months (mean, 35.7 months). Twenty-three eyes (74.2%)
      achieved a stable ocular surface. Overall, the mean visual acuity improved from
      20/1000 to 20/165. Twenty eyes (64.5%) underwent subsequent penetrating
      keratoplasty. Fourteen corneal transplant grafts (70.0%) were successful, and six
      (30.0%) failed. Nineteen (90.5%) of 21 eyes receiving systemic immunosuppression
      obtained a stable ocular surface, whereas only 4 (40.0%) of 10 eyes not receiving
      systemic immunosuppression achieved ocular surface stability (P < 0.01).
      CONCLUSIONS: KLAL is effective in treating aniridic keratopathy. Patients
      receiving systemic immunosuppression have a greater likelihood of achieving
      ocular surface stability and improved visual acuity compared with those who
      receive only topical immunosuppression.

PMID- 12511358
TI  - Atopy: a patient-specific risk factor for diffuse lamellar keratitis.
AB  - OBJECTIVE: To identify whether atopy is a patient-specific risk factor for the
      development of diffuse lamellar keratitis (DLK) after laser in situ
      keratomileusis (LASIK). DESIGN: Retrospective survey study. PARTICIPANTS: Three
      hundred sixty consecutive patients who underwent same-day bilateral myopic
      astigmatic primary LASIK procedures during March 1, 2000, through July 31, 2000.
      METHODS: We collected data for 360 consecutive patients undergoing LASIK during a
      4-month period. On preoperative medical history questionnaires, patients self
      identified whether they were atopic. All patients also indicated whether they
      were taking antiallergy medications or were untreated for allergy. MAIN OUTCOME
      MEASURES: The incidence of DLK after LASIK surgery. RESULTS: The risk of DLK in
      untreated atopic patients was much greater than the risk of DLK among nonatopics
      (odds ratio, 5.85; 95% confidence interval, 2.89-11.85; P = 0.001). However, the
      risk of DLK among atopic patients taking an oral systemic nonsedating histamine
      receptor 1 antagonist and among nonatopic patients did not differ significantly
      (odds ratio, 0.54; 95% confidence interval, 0.12-2.46; P = 0.43). CONCLUSIONS:
      Atopy is a patient-specific risk factor for the development of DLK after primary
      bilateral LASIK for either myopia or myopic astigmatism. Atopic individuals
      benefit from preoperative treatment to minimize the incidence of DLK and the
      potential for visual loss.

PMID- 12511359
TI  - Trends in contact lens-associated microbial keratitis in Southern India.
AB  - OBJECTIVE: To review the microbiologic profile, clinical course, treatment, and
      outcome in patients with contact lens-associated microbial keratitis in the
      setting of a tertiary eye care center in a developing country in the Tropics.
      DESIGN: Retrospective noncomparative case series selected from an ongoing
      prospective series. PARTICIPANTS: Twenty-eight subjects examined in the contact
      lens clinic of L. V. Prasad Eye Institute, Hyderabad, south India, between
      February 1991 and September 2000, who presented with corneal stromal infiltrate
      on slit-lamp examination, were included in the study. INTERVENTION: All patients
      underwent standard diagnostic microbiologic evaluation and smear and culture
      guided topical antimicrobial therapy. Penetrating keratoplasty was performed in
      some patients. MAIN OUTCOME MEASURES: Culture results and clinical response to
      antimicrobial therapy. RESULTS: Twenty eight (0.11%) of 23,889 contact lens
      wearing patients presented with laboratory-proven infectious keratitis; this
      constituted 0.56% of 4967 corneal ulcer patients seen during the same period.
      Most (15/28) of the patients wore soft contact lenses on a daily basis. Rigid gas
      permeable lenses were worn by six patients, therapeutic bandage contact lenses by
      four, and Silsoft lenses by four. Laboratory results showed bacterial infections
      in 25 patients (89.2%); Pseudomonas was the most common organism (13/25; 52%).
      Acanthamoeba, herpes simplex virus, and Aspergillus niger were isolated in one
      case each. Laboratory-based medical therapy led to the healing of ulcers in 24
      (85.7%) of 28 patients, whereas 4 patients required penetrating keratoplasty.
      Most of the organisms were sensitive to antibiotics. CONCLUSIONS: Contact lens
      associated microbial keratitis is rare in southern India. Soft contact lens wear
      is the most common risk factor; Pseudomonas keratitis is the predominant
      causative agent. Fungal, viral, and Acanthamoeba keratitis are rare. The
      offending bacteria are usually sensitive to antibiotics, and the treatment
      outcome with medical therapy is good.

PMID- 12511360
TI  - Lidocaine 2% gel versus lidocaine 4% unpreserved drops for topical anesthesia in
      cataract surgery: a randomized controlled trial.
AB  - OBJECTIVE: To compare intracameral levels and clinical efficacy of lidocaine 2%
      gel with lidocaine 4% unpreserved drops. DESIGN: Double-blind, randomized, one
      surgeon, controlled trial. PARTICIPANTS: One hundred seven consecutive cataract
      cases eligible for topical anesthesia. INTERVENTION: Patients were randomly
      assigned to receive 20 mg of lidocaine either as lidocaine 2% gel (1 ml) or as
      lidocaine 4% unpreserved eyedrops (0.5 ml) before clear corneal
      phacoemulsification. MAIN OUTCOME MEASURES: Aqueous samples were taken to measure
      lidocaine intraocular levels. Intraoperative pain was quantified a few minutes
      after surgery using a 0 to 10 visual analog scale. SECONDARY OUTCOME MEASURES:
      Patients were asked to grade the degree to which they were bothered by tissue
      manipulation. The surgeon graded patients' cooperation. The anesthesiologist
      recorded any increase in pulse or blood pressure and the need for supplemental
      topical anesthesia or intravenous sedation. Duration of surgery and
      intraoperative complications were also recorded. RESULTS: In the gel group
      intracameral lidocaine levels were significantly higher (P < 0.001) and patient
      reported intraoperative pain scores were significantly lower (P = 0.026).
      Patients in the gel group were bothered by tissue manipulation to a lesser extent
      (P = 0.028), and their cooperation was better (P = 0.002). Increases in blood
      pressure were more frequent in the eyedrops group. Supplemental anesthesia was
      required in two cases (3.70%) in the gel group versus eight cases in the eyedrops
      group (15.09%). No correlation between intracameral lidocaine levels and
      intraoperative pain scores was found (r = -0.026, P = 0.789). CONCLUSIONS: If
      administered by means of gel, the same amount of lidocaine gives significantly
      higher intracameral levels of lidocaine, better analgesia, better patient
      cooperation, and less need for intraoperative supplemental anesthesia. Lower pain
      scores do not correlate with intracameral lidocaine levels.

PMID- 12511361
TI  - Toric phakic intraocular lens: European multicenter study.
AB  - OBJECTIVE: To evaluate safety, efficacy, predictability, stability,
      complications, and patient satisfaction after implantation of Artisan toric
      phakic intraocular lenses (TPIOLs) for the correction of myopia or hyperopia with
      astigmatism. DESIGN: Prospective, nonrandomized, comparative (self-controlled)
      multicenter trial. PARTICIPANTS: Seventy eyes of 53 patients (mean, 35 years;
      range, 22-59 years) with preoperative spherical equivalent between +6.50 and 
      21.25 diopters (D) and cylinder between 1.50 and 7.25 D. METHODS: Seventy eyes
      underwent implantation of a TPIOL with an optical zone of 5.0 mm (Artisan,
      Ophtec, Groningen, The Netherlands). The dioptric power of the intraocular lens
      was calculated by considering refraction, keratometry, and anterior chamber
      depth. The follow-up was 6 months in all cases. Lenses were available in powers
      ranging from +12.0 D to -23.5 D (spherical equivalent) in 0.5-D increments, with
      additional cylinder from 1.0 D to 7.0 D, also in 0.5-D increments. MAIN OUTCOME
      MEASURES: The main parameters assessed were best spectacle-corrected visual
      acuity (BSCVA), uncorrected visual acuity (UCVA), refraction, endothelial cell
      count (ECC), intraocular pressure, slit-lamp biomicroscopy, indirect
      ophthalmoscopy, subjective complaints, and patient satisfaction. RESULTS: Eyes
      were divided into group A, myopia (n = 48), with an average preoperative
      spherical equivalent of -8.90 +/- 4.52 D, and group B, hyperopia (n = 22), with
      an average preoperative spherical equivalent of +3.25 +/- 1.98 D. No eyes in
      either group experienced a loss in BSCVA, and 46 eyes gained 1 or more lines of
      their preoperative BSCVA. In 62 eyes (88.6%), UCVA was 20/40 or better. There was
      a significant reduction in spherical errors and astigmatism in all cases after
      surgery. All eyes of both groups were within +/-1.00 D of target refraction, and
      51 eyes (72.9%) were within +/-0.50 D of target refraction. There was a 4.5% mean
      total loss of ECC during the first 6 months. No serious complications were
      observed. Overall patient satisfaction was very high. CONCLUSIONS: Six-month
      clinical trial results demonstrate that implantation of the Artisan TPIOL safely,
      predictably, and effectively reduced or eliminated high ametropia and astigmatism
      with one procedure. The refractive effect was stable at 6 months after surgery.

PMID- 12511362
TI  - Ultrasound biomicroscopy examination of posterior chamber phakic intraocular lens
      position.
AB  - OBJECTIVE: To better elucidate the in vivo position of the Collamer posterior
      chamber phakic intraocular lens (PCPIOL) and its relationship to the iris and the
      crystalline lens and to analyze possible variations over time. DESIGN:
      Prospective observational case series. PARTICIPANTS: Eighteen eyes of nine
      patients were included. INTERVENTION: A Staar Collamer implantable PCPIOL was
      implanted for the correction of high myopia. MAIN OUTCOME MEASURES: The eyes were
      studied with a 50-MHz ultrasound biomicroscopy UBM 840. The exact PCPIOL position
      and the distances between it and the crystalline lens were measured at 3, 6, and
      12 months after surgery. RESULTS: There were no intraoperative complications. In
      13 eyes (72.22%), contact between the PCPIOL and the crystalline lens was found
      at some time during follow-up. In 3 eyes (16.6%), central contact could be
      demonstrated. We also observed that the contact zone and its extension can vary
      over time. In 2 eyes, rotation of the lens was observed. CONCLUSIONS: We found
      contact between the PCPIOL and the crystalline lens in a high percentage of
      cases. There was also mobility of the lens in the posterior chamber, especially
      in the anteroposterior plane, and, as a consequence, both the contact zone and
      its extension would vary over time.

PMID- 12511363
TI  - Penetrating needle injury of the eye causing cataract in children.
AB  - PURPOSE: To review the presentation, management, and outcome of children with
      cataract caused by ocular needle penetration. DESIGN: Retrospective,
      noncomparative interventional case series. PARTICIPANTS: Forty-two children with
      cataract caused by ocular needle penetration. INTERVENTION: Cataract surgery.
      MAIN OUTCOME MEASURES: Best-corrected postoperative visual acuity. RESULTS:
      Injuries were unintentional and occurred during unsupervised play. The type of
      needle involved was hypodermic in 24 cases, sewing in 7, and undetermined in 11.
      Endophthalmitis developed in 14 cases and retinal detachment in 6.
      Endophthalmitis occurred in 12 cases (50%) of hypodermic needle injury but in no
      case of sewing needle injury. With a mean postoperative follow-up of 2.3 years,
      the best-corrected visual acuity was 20/40 or better in 19 cases, 20/50 to 20/80
      in 7, 20/100 to counting fingers in 6, light perception in 1, no light perception
      in 6, and undetermined in 3. Eyes with endophthalmitis and/or retinal detachment
      had a worse visual prognosis. CONCLUSIONS: Ocular penetration causing cataract
      occurred in children during unsupervised play with inadequately stored or
      disposed of hypodermic or sewing needles. Endophthalmitis occurred frequently in
      injuries caused by hypodermic needles but not in those caused by sewing needles.
      Visual outcome after management was good in approximately half of the cases
      especially if endophthalmitis or retinal detachment did not develop.

PMID- 12511365
TI  - Reliability of nerve fiber layer thickness measurements using optical coherence
      tomography in normal and glaucomatous eyes.
AB  - OBJECTIVE: To evaluate the reliability of nerve fiber layer (NFL) thickness
      measurements by optical coherence tomography (OCT) in normal and glaucomatous
      eyes. DESIGN: Prospective, comparative, observational case series and instrument
      validation study. PARTICIPANTS: Twenty-four glaucomatous patients were compared
      with 24 gender- and age-matched normal subjects. METHODS: Each individual
      underwent OCT measurements of NFL thickness. Five repetitions of a series of
      scans on five separate occasions within a 0.5-month period were performed. Each
      eye was scanned at three different nerve head programs (1.5 radius [R], R = 1.73
      mm, 2.0 R). For each option (1.5 R, R = 1.73 mm, and 2.0R) and region (superior,
      inferior, temporal, nasal, and overall mean), variance components and intraclass
      correlation coefficients were determined using repeated measures regression. In
      these models, NFL thickness, as measured by OCT, was assumed to have three
      variance components: intersubject, intervisit (within-subject between-dates), and
      intravisit (within-subject within-date). The intraclass correlation coefficient
      (intersubject variance/total variance) was used as a measure of reliability. MAIN
      OUTCOME MEASURES: Measurements of NFL thickness using OCT were performed.
      RESULTS: Reliability values, as measured by intraclass correlation coefficients,
      resulted as follows: 1.5 R, 0.54/0.52 (normal/glaucoma); R = 1.73 mm, 0.50/0.50;
      2.0 R, 0.49/0.50. CONCLUSIONS: Our results indicate that the recent commercially
      available OCT provides reliable NFL thickness measurements in both healthy and
      glaucomatous eyes with each circle radius tested. The greatest amount of
      variability can be attributed to intersubject differences.

PMID- 12511364
TI  - Optical coherence tomography measurement of macular and nerve fiber layer
      thickness in normal and glaucomatous human eyes.
AB  - PURPOSE: To evaluate the hypothesis that macular thickness correlates with the
      diagnosis of glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: We studied
      367 subjects (534 eyes), including 166 eyes of 109 normal subjects, 83 eyes of 58
      glaucoma suspects, 196 eyes of 132 early glaucoma patients, and 89 eyes of 68
      advanced glaucoma patients. METHODS: We used optical coherence tomography (OCT)
      to measure macular and nerve fiber layer (NFL) thickness and to analyze their
      correlation with each other and with glaucoma status. We used both the commercial
      and prototype OCT units and evaluated correspondence between measurements
      performed on the same eyes on the same days. MAIN OUTCOME MEASURE: Macular and
      NFL thickness as measured by OCT. RESULTS: All NFL parameters both in prototype
      and commercial OCT units were statistically significantly different comparing
      normal subjects and either early or advanced glaucoma (P < 0.001). Inner ring,
      outer ring, and mean macular thickness both in prototype and commercial OCT
      devices were found to be significantly different between normal subjects and
      advanced glaucomatous eyes (P < 0.001). The outer ring was the only macular
      parameter that could significantly differentiate between normal and early
      glaucoma with either the prototype or commercial OCT unit (P = 0.003, P = 0.008,
      respectively). The area under the receiver operator characteristic (AROC) curves
      comparing mean NFL thickness between normal and advanced glaucomatous eyes was
      1.00 for both the prototype and commercial OCT devices for eyes scanned on both
      machines on the same day. The AROC comparing mean macular thickness in normal and
      advanced glaucomatous eyes scanned on both machines on the same day was 0.88 for
      the prototype OCT device and 0.80 for the commercial OCT. CONCLUSIONS: Both
      macular and NFL thickness as measured by OCT showed statistically significant
      correlations with glaucoma, although NFL thickness showed a stronger association
      than macular thickness. There was good correspondence between findings using both
      the prototype and commercial OCT units. Macular and NFL thickness measurements
      made with OCT may have usefulness in the clinical assessment of glaucoma.

PMID- 12511366
TI  - Misleading statistical calculations in far-advanced glaucomatous visual field
      loss.
AB  - OBJECTIVE: In this study, the capability of statistical analysis indices to
      characterize static automated visual fields (VFs) accurately in cases of far
      advanced glaucoma was assessed. DESIGN: Retrospective observational case series.
      PARTICIPANTS: Sixteen eyes of 15 patients with end-stage glaucoma and evidence of
      collapse of VF statistical analysis indices were included in the study. METHODS:
      End-stage glaucoma was defined as vertical cup-to-disc ratio of 0.9 or more, mean
      deviation less than -24 dB and with only a central or temporal island remaining
      in the VF gray scale. Collapse of statistical indices was defined as any of the
      following: pattern deviation probability plot without a single VF location
      showing P < 0.5%; corrected pattern standard deviation (CPSD) and pattern
      standard deviation (PSD) probability less than 5% or within normal limits (WNL);
      short-term fluctuation (SF) probability WNL; glaucoma hemifield test (GHT) not
      outside normal limits (ONL); or presence of a low patient reliability comment
      triggered by 40% or more false-negative (FN) responses. MAIN OUTCOME MEASURES:
      Visual field statistical indices. RESULTS: Of the 16 VFs showing misleading
      statistical calculations, 9 of 16 eyes had a normal pattern deviation probability
      plot. The PSD, SF, and CPSD parameters were normal or barely outside the normal
      range in 4 of 16, 10 of 16, and 5 of 16 eyes, respectively. The GHT was ONL in 7
      of 13 eyes, borderline with generalized reduction of sensitivity (GRS) in three
      eyes, and only GRS in two additional eyes. Low patient reliability was triggered
      because of an FN score of 40% or more in 10 of 16 eyes. CONCLUSIONS: Statistical
      indices are crucial for the interpretation of automated static VFs. However, in
      end-stage glaucomatous VF loss, both summary statistical indices and reliability
      indices may not detect abnormality, thus misleading the casual observer.

PMID- 12511367
TI  - Changes in optic nerve head blood flow after therapeutic intraocular pressure
      reduction in glaucoma patients and ocular hypertensives.
AB  - PURPOSE: To detect and quantify changes in optic nerve head (ONH) and
      peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF) in
      open-angle glaucoma (OAG) and ocular hypertension (OHT) after therapeutic
      intraocular pressure (IOP) reduction. DESIGN: Prospective, nonrandomized, self
      controlled trial. PARTICIPANTS: Twenty patients with OAG and 20 patients with OHT
      with clinical indications for therapeutic IOP reduction were prospectively
      enrolled. INTERVENTION: IOP reduction was achieved by medical, laser, or surgical
      therapy. All patients had IOP reductions more than 20% and a minimum of 4 weeks
      follow-up. MAIN OUTCOME MEASURES: Blood flow measurements were performed by SLDF
      analysis software (version 3.3) using Heidelberg Retina Flowmeter images.
      Statistical evaluations were performed on both groups using a two-tailed
      distribution paired t test. RESULTS: Twenty patients with OAG had a mean IOP
      reduction of 37% after treatment. In these patients, mean (+/- standard
      deviation) rim blood flow increased by 67% (from 158 +/- 79 arbitrary units to
      264 +/- 127 arbitrary units, P = 0.001), whereas mean temporal peripapillary
      retinal flow decreased by 7.4% (P = 0.24), and mean nasal peripapillary retinal
      flow increased by 0.3% (P = 0.96). Twenty OHT patients had a mean IOP reduction
      of 33% after treatment. In contrast to the OAG group, neither the mean rim blood
      flow (7.5% increase from 277 +/- 158 arbitrary units to 298 +/- 140 arbitrary
      units, P = 0.41) nor the mean temporal (P = 0.35) or nasal (P = 0.88)
      peripapillary retinal flow changed significantly. CONCLUSIONS: For a similar
      percentage of IOP reduction, OAG patients had a statistically significant
      improvement of blood flow in the neuroretinal rim of the ONH, whereas OHT
      patients did not demonstrate such a change. Peripapillary retinal blood flow,
      expected to be affected less in glaucoma, remained stable in both groups. In
      addition to indicating a response to therapy in OAG patients, the reported
      changes in rim perfusion suggest that ONH autoregulation may be defective in OAG
      while intact in OHT.

PMID- 12511368
TI  - Refractive errors, intraocular pressure, and glaucoma in a white population.
AB  - OBJECTIVE: To examine the relation of refractive errors to glaucoma and
      intraocular pressure (IOP) in a defined white population. DESIGN: Population
      based cross-sectional and follow-up study. PARTICIPANTS: Persons aged 43 to 86
      years living in Beaver Dam, Wisconsin (n = 4926). METHODS: All participants
      received a standardized assessment of refraction, IOP, and glaucoma at baseline
      (1988-1990), with IOP remeasured 5 years later (1993-1995). Refraction was
      defined at baseline as follows: myopia as spherical equivalent of -1.00 diopters
      (D) or less, emmetropia as -0.75 to +0.75 D, and hyperopia as +1.00 D or more.
      MAIN OUTCOME MEASURES: Relation of baseline refraction to prevalent glaucoma
      (defined from IOP, optic disc, and visual field criteria) and incident ocular
      hypertension (defined as IOP more than 21 mmHg at the 5-year examination in eyes
      with IOP of 21 mmHg or less at baseline). RESULTS: A myopic refraction was
      correlated with increasing IOP at baseline (P < 0.001). After controlling for age
      and gender, persons with myopia were 60% more likely to have prevalent glaucoma
      than those with emmetropia (odds ratio [OR], 1.6; 95% confidence interval [CI],
      1.1, 2.3). In contrast, controlling for age, gender, and baseline IOP, persons
      with hyperopia were 40% more likely to have incident ocular hypertension than
      those who were emmetropic at baseline (OR, 1.4; 95% CI, 1.0, 2.0). Myopia was not
      related to incident ocular hypertension. CONCLUSIONS: In these population-based
      data, there was a cross-sectional association of myopia with higher IOP and
      prevalent glaucoma. Similar associations have been found in previous studies.
      Hyperopia may be associated with 5-year risk of ocular hypertension, a finding
      that needs further investigation.

PMID- 12511370
TI  - Sunscreen use and malignant melanoma risk: the jury is still out.

PMID- 12511371
TI  - Eugenics and public health.

PMID- 12511373
TI  - Optimal SES indicators cannot be prescribed across all outcomes.

PMID- 12511375
TI  - Quality, affordable health care for all Americans.

PMID- 12511376
TI  - Why "Rekindling Reform?".

PMID- 12511377
TI  - Universal health insurance in the United States: reflections on the past, the
      present, and the future.

PMID- 12511378
TI  - Health care reform: lessons from Canada.
AB  - Although Canadian health care seems to be perennially in crisis, access, quality,
      and satisfaction in Canada are relatively high, and spending is relatively well
      controlled. The Canadian model is built on a recognition of the limits of markets
      in distributing medically necessary care. Current issues in financing and
      delivering health care in Canada deserve attention. Key dilemmas include
      intergovernmental disputes between the federal and provincial levels of
      government and determining how to organize care, what to pay for
      (comprehensiveness), and what incentive structures to put in place for payment.
      Lessons for the United States include the importance of universal coverage, the
      advantages of a single payer, and the fact that systems can be organized on a
      subnational basis.

PMID- 12511379
TI  - Universal health care: lessons from the British experience.
AB  - Britain's National Health Service (NHS) was established in the wake of World War
      II amid a broad consensus that health care should be made available to all. Yet
      the British only barely succeeded in overcoming professional opposition to form
      the NHS out of the prewar mixture of limited national insurance, various
      voluntary insurance schemes, charity care, and public health services. Success
      stemmed from extraordinary leadership, a parliamentary system of government that
      gives the winning party great control, and a willingness to make major
      concessions to key stakeholders. As one of the basic models emulated worldwide,
      the NHS-in both its original form and its current restructuring-offers a number
      of relevant lessons for health reform in the United States.

PMID- 12511380
TI  - The health care system under French national health insurance: lessons for health
      reform in the United States.
AB  - The French health system combines universal coverage with a public-private mix of
      hospital and ambulatory care and a higher volume of service provision than in the
      United States. Although the system is far from perfect, its indicators of health
      status and consumer satisfaction are high; its expenditures, as a share of gross
      domestic product, are far lower than in the United States; and patients have an
      extraordinary degree of choice among providers. Lessons for the United States
      include the importance of government's role in providing a statutory framework
      for universal health insurance; recognition that piecemeal reform can broaden a
      partial program (like Medicare) to cover, eventually, the entire population; and
      understanding that universal coverage can be achieved without excluding private
      insurers from the supplementary insurance market.

PMID- 12511381
TI  - Insights from health care in Germany.
AB  - German Statutory Health Insurance (national health insurance) has remained
      relatively intact over the past century, even in the face of governmental change
      and recent reforms. The overall story of German national health insurance is one
      of political compromise and successful implementation of communitarian values.
      Several key lessons from the German experience can be applied to the American
      health care system.

PMID- 12511382
TI  - Health reform in Brazil: lessons to consider.
AB  - US analysts and decisionmakers interested in comparative health policy typically
      turn to European perspectives, but Brazil-notwithstanding its far smaller gross
      domestic product and lower per capita health expenditures and technological
      investments-offers an example with surprising relevance to the US health policy
      context. Not only is Brazil comparable to the United States in size,
      racial/ethnic and geographic diversity, federal system of government, and
      problems of social inequality. Within the health system the incremental nature of
      reforms, the large role of the private sector, the multitiered patchwork of
      coverage, and the historically large population excluded from health insurance
      coverage resonate with health policy challenges and developments in the United
      States.

PMID- 12511383
TI  - Health care reform in South Korea: success or failure?
AB  - South Korea is one of the world's most rapidly industrializing countries. Along
      with industrialization has come universal health insurance. Within the span of 12
      years, South Korea went from private voluntary health insurance to government
      mandated universal coverage. Since 1997, with the intervention of the
      International Monetary Fund, Korean national health insurance (NHI) has
      experienced deficits and disruption. However, there are lessons to be drawn for
      the United States from the Korean NHI experience.

PMID- 12511384
TI  - Comparing health systems in four countries: lessons for the United States.
AB  - The Rekindling Reform initiative examined the health systems of 4 countries:
      Canada, France, Germany, and Great Britain (United Kingdom). From the 4 country
      reports published in this issue of the American Journal of Public Health, 10
      crosscutting themes emerge: (1) coverage, (2) funding, (3) costs, (4) providers,
      (5) integration, (6) markets, (7) analysis, (8) supply, (9) satisfaction, and
      (10) leadership. Lessons for the United States are presented under each point.

PMID- 12511385
TI  - Medical care for all the people. 1944.

PMID- 12511386
TI  - Henry E. Sigerist: medical historian and social visionary.

PMID- 12511387
TI  - Lessons for (and from) America.
AB  - Drawing lessons from international experience for health care reform in the
      United States requires striking a difficult balance between historical
      determinism and free will, between cynical pessimism and naive optimism. The key
      to this puzzle may lie in a paradox: the United States is the most successful
      exporter of public health policy ideas and instruments yet has failed to build an
      effective health care system. General ideas (like notions about the role of
      competition) and microinstruments (like diagnosis-related groups) travel better
      than do health care systems. Ideas can be adapted to local circumstances, and
      instruments may easily fit into preexisting systems. Importing systems from
      countries with different histories and institutions would require a tectonic
      shift in the American political landscape.

PMID- 12511388
TI  - Policy without politics: the limits of social engineering.
AB  - The extent of coverage provided by a country's health services is directly
      related to the level of development of that country's democratic process (and its
      power relations). The United States is the only developed country whose
      government does not guarantee access to health care for its citizens. It is also
      the developed country with the least representative and most insufficient
      democratic institutions, owing to the constitutional framework of the political
      system, the privatization of the electoral process, and the enormous power of
      corporate interests in both the media and the political process. As international
      experience shows, without a strong labor-based movement willing to be radical in
      its protests, a universal health care program will never be accepted by the US
      establishment.

PMID- 12511389
TI  - What other programs can teach us: increasing participation in health insurance
      programs.
AB  - Many uninsured Americans are already eligible for free or low-cost public
      coverage through Medicaid or Children's Health Insurance Program (CHIP) but do
      not "take up" that coverage. However, several other public programs, such as food
      stamps and unemployment insurance, also have less-than-complete take-up rates,
      and take-up rates vary considerably among programs. This article examines the
      take-up literature across a variety of programs to learn what effects
      nonfinancial features, such as administrative complexity, have on take-up. We
      find that making benefit receipt automatic is the most effective means of
      ensuring high take-up, while there is little evidence that stigma is important.

PMID- 12511390
TI  - Health care reform and social movements in the United States.
AB  - Because of the importance of grassroots social movements, or "change from below,"
      in the history of US reform, the relationship between social movements and
      demands for universal health care is a critical one. National health reform
      campaigns in the 20th century were initiated and run by elites more concerned
      with defending against attacks from interest groups than with popular
      mobilization, and grassroots reformers in the labor, civil rights, feminist, and
      AIDS activist movements have concentrated more on immediate and incremental
      changes than on transforming the health care system itself. However, grassroots
      health care demands have also contained the seeds of a wider critique of the
      American health care system, leading some movements to adopt calls for universal
      coverage.

PMID- 12511391
TI  - Struggles for national health reform in the United States.

PMID- 12511392
TI  - Rekindling reform--how goes business?
AB  - Employers were a major cause of the failure of President Clinton's Health
      Security bill. This did not have to be so. The substantive and political factors
      that caused employers to turn against the Clinton Plan could prove instructive in
      the next reform effort. The unwillingness of employers who do provide benefits to
      engage seriously in the struggle over health care reform contributes to
      maintaining the status quo that penalizes them while rewarding employers who fail
      to provide coverage. The lessons that can be learned from the Clinton Plan
      debate, if heeded by both employers and health reform advocates, raise hope that
      key elements of the business community can play a positive role in the next
      comprehensive health reform effort.

PMID- 12511393
TI  - Labor rekindles reform.
AB  - The health care crisis is back. There is intensifying sentiment across the
      country that universal coverage is our only way out. The labor movement has used
      historically such opportunities for change to win health benefits at the
      bargaining table and strengthen the social safety net. Eighty years of
      incremental victories and many failed attempts at major health reform have taught
      labor a crucial lesson: we must build a powerful grassroots movement to drive our
      effort to achieve universal coverage, or it is doomed to be corrupted by those
      wedded to the status quo. Now is the right time for reform.

PMID- 12511394
TI  - APHA policies on universal health care: health for a few or health for all?
AB  - The American Public Health Association (APHA) has long advocated the development
      of a system of universal health care for all US residents. APHA has adopted
      several policies on this topic that stress the financing of the system of
      universal health care under a single-payer mechanism. However, this approach has
      never been adopted by US policymakers. The need for universal health coverage in
      the United States is growing more acute, and failure to provide such coverage
      threatens the health status of the public. I propose an alternative approach to
      the single-payer system that is based on incremental extension of existing
      coverage mechanisms, accompanied by fundamental reform of the health care
      delivery system. This approach is in keeping with the traditional methods of
      policy development in the United States, and I urge APHA to assume leadership in
      advocating it.

PMID- 12511395
TI  - National health insurance or incremental reform: aim high, or at our feet?
AB  - Single-payer national health insurance could cover the uninsured and upgrade
      coverage for most Americans without increasing costs; savings on insurance
      overhead and other bureaucracy would fully offset the costs of improved care. In
      contrast, proposed incremental reforms are projected to cover a fraction of the
      uninsured, at great cost. Moreover, even these projections are suspect; reforms
      of the past quarter century have not stemmed the erosion of coverage. Despite
      incrementalists' claims of pragmatism, they have proven unable to shepherd
      meaningful reform through the political system. While national health insurance
      is often dismissed as ultra left by the policy community, it is dead center in
      public opinion. Polls have consistently shown that at least 40%, and perhaps 60%,
      of Americans favor such reform.

PMID- 12511396
TI  - Affordable health insurance for all is possible by means of a pragmatic approach.
AB  - America can attain affordable health insurance coverage for all by using a
      pragmatic approach. Such an effort must accommodate the realities of the American
      health care system and resist the temptation to propose radical restructuring.
      The congressional strategy for universal health care described here was developed
      by the American College of Physicians-American Society of Internal Medicine. It
      builds on the strengths of the current pluralistic system by combining the
      benefits of public health plans such as Medicaid and the State Children's Health
      Insurance Program with a more competitive and affordable private insurance
      market. The health care system has reached a crisis point. Allowing the status
      quo to continue courts certain disaster.

PMID- 12511397
TI  - Universal coverage and public health: new state studies.
AB  - Recent evaluations of the California Health Service Plan (CHSP) confirmed that
      financing health care through a single government payer can provide universal
      coverage-while saving significantly on health care spending-to a degree
      unparalleled by alternative approaches. Public ownership of the delivery system
      can further provide authority and accountability for critical reforms that
      improve the population's health and quality of care, including coordination of
      the delivery system. The federal government's State Planning Grant Program
      provides states with funding to develop plans to cover their uninsured
      populations. California created a Health Care Options Project that requested
      proposals that could expand coverage and contracted with a financial modeler and
      a qualitative analyst to evaluate the resulting plans. The CHSP was one of 9
      plans evaluated through this process.

PMID- 12511398
TI  - The movement for universal health insurance: finding common ground.
AB  - Before 1971, all proposals for universal health insurance were based on private
      sector financing and administration. After 1971, universal health insurance plans
      relying on the private sector complicated efforts of the universal health
      insurance movement. To forge as broad a movement for universal health insurance
      as possible, it may be worthwhile for universal health insurance advocates of
      different persuasions to seek common ground on the basis of a set of goals for a
      new health care system. The goals can serve as a measuring stick to determine
      which health insurance plans are worthy of support.

PMID- 12511399
TI  - Rekindling reform: principles and goals.
AB  - Members of the Rekindling Reform Steering Committee collaborated over a period of
      several months in early 2002 to develop a set of principles and goals to help
      guide and define the group's efforts for comprehensive health care reform in the
      United States. The next step is to circulate this document to the sponsoring
      organizations for their approval. This document is, then, a work in progress,
      subject to revision as the process of discussion and review continues. These
      principles provide a sense of the lessons members of the Rekindling Reform
      Steering Committee have learned from their study of other countries' universal
      health care systems, and how those lessons have informed their thinking about the
      nature of the health care reform needed in United States.

PMID- 12511400
TI  - A joint urban planning and public health framework: contributions to health
      impact assessment.
AB  - A joint urban planning and public health perspective is articulated here for use,
      in health impact assessment. Absent a blueprint for a coherent and supportive
      structure on which to test our thinking, we are bound to fall flat. Such a
      perspective is made necessary by the sheer number of people living in cities
      throughout the world, the need for explicit attention to land use and
      transportation systems as determinants of population health, and the dearth of
      useful indicators of the built environment for monitoring progress. If explicit
      attention is not paid to the overarching goals of equality and democracy, they
      have little if any chance of being realized in projects, programs, and policies
      that shape the built environment and therefore the public's health.

PMID- 12511401
TI  - Is social capital the key to inequalities in health?
AB  - There has been vigorous debate between the "social capital" and "neomaterialist"
      interpretations of the epidemiological evidence regarding socioeconomic
      determinants of health. We argue that levels of income inequality, social
      capital, and health in a community may all be consequences of more macrolevel
      social and economic processes that influence health across the life course. We
      discuss the many reasons for the prominence of social capital theory, and the
      potential drawbacks to making social capital a major focus of social policy.
      Intervening in communities to increase their levels of social capital may be
      ineffective, create resentment, and overload community resources, and to take
      such an approach may be to "blame the victim" at the community level while
      ignoring the health effects of macrolevel social and economic policies.

PMID- 12511402
TI  - Intermittent lack of health insurance coverage and use of preventive services.
AB  - OBJECTIVES: This study examined the association between intermittent lack of
      health insurance coverage and use of preventive health services. METHODS:
      Analyses focused on longitudinal data on insurance status and preventive service
      use among a national sample of US adults who participated in the Health and
      Retirement Study. RESULTS: Findings showed that, among individuals who obtain
      insurance coverage after histories of intermittent coverage, relatively long
      periods may be necessary to reestablish clinically appropriate care patterns.
      Increasing periods of noncoverage led to successively lower rates of use of most
      preventive services. CONCLUSIONS: Intermittent lack of insurance coverage-even
      across a relatively long period-results in less use of preventive services.
      Studies that examine only current insurance status may underestimate the
      population at risk from being uninsured.

PMID- 12511403
TI  - Vulnerability and the patient-practitioner relationship: the roles of gatekeeping
      and primary care performance.
AB  - OBJECTIVES: We examined whether patients' perceptions of their relationships with
      primary care practitioners (PCPs) vary by vulnerability status and assessed the
      extent to which gatekeeping arrangements and primary care performance moderate
      potential disparities. METHODS: We used the nationally representative 1996-1997
      Community Tracking Study Household Survey as our data source. RESULTS: Whites
      reported better patient-practitioner relationships than minorities. Requirements
      that patients select a PCP and obtain referral authorization neither reduced nor
      exacerbated racial disparities in the patient-practitioner relationship. On the
      other hand, access to and continuity with a PCP substantively reduced
      disparities, especially for the most vulnerable group. CONCLUSIONS: Enhancing
      primary care performance may reduce some of the barriers to care experienced by
      vulnerable populations, thereby improving patients' relationships with their
      PCPs.

PMID- 12511404
TI  - Child participation in WIC: Medicaid costs and use of health care services.
AB  - OBJECTIVES: We used data from birth certificates, Medicaid, and the Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC) to examine
      the relationship of child participation in WIC to Medicaid costs and use of
      health care services in North Carolina. METHODS: We linked Medicaid enrollment,
      Medicaid paid claims, and WIC participation files to birth certificates for
      children born in North Carolina in 1992. We used multiple regression analysis to
      estimate the effects of WIC participation on the use of health care services and
      Medicaid costs. RESULTS: Medicaid-enrolled children participating in the WIC
      program showed greater use of all types of health care services compared with
      Medicaid-enrolled children who were not WIC participants. CONCLUSIONS: The health
      care needs of low-income children who participate in WIC may be better met than
      those of low-income children not participating in WIC.

PMID- 12511405
TI  - Molecular heterogeneity in MCL defined by the use of specific VH genes and the
      frequency of somatic mutations.
AB  - This study explores whether the presence of somatic mutations or a biased use of
      IgV(H) genes were associated with the clinical features in a series of 96
      patients with mantle cell lymphoma (MCL). The cases were studied by seminested
      polymerase chain reaction using primers from the FR1 and J(H) regions. There was
      an unexpectedly high frequency of somatic mutations, with 29 of 103 sequences
      showing more than 2% of mutations. Biased usage of specific V(H) segments was
      also found; the most widely used genes in this series were V(H)3-21 (10 cases),
      V(H)3-23 (9 cases), V(H)4-34 (11 cases), and V(H)4-59 (9 cases). V(H) mutation
      frequency, taking into account different thresholds, did not distinguish
      different overall survival probabilities. Nevertheless, a more frequent use of
      V(H)3-21 or V(H)4-59 (8 of 18) was observed in the group of long-term survivors
      (18 cases > 5 years; P <.01). None of these long-term survivors presented the
      V(H)3-23 gene rearrangement. As in other lymphoproliferative disorders, the
      expression of CD38 or p53 or both was associated with a poorer survival
      probability. This nonrandom usage of IgV(H) segments suggests that specific
      antigens may play a pathogenically relevant role in the genesis or progression of
      subsets of MCL cases and may help in distinguishing a significant group of MCL
      long-term survivors.

PMID- 12511406
TI  - Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients:
      gains of the chromosomal segment 3q26q29 as an adverse risk factor.
AB  - Fanconi anemia (FA) is a condition that induces susceptibility to bone marrow
      failure, myelodysplastic syndrome (MDS), and leukemia. We report on a high
      incidence of expanding clonal aberrations with partial trisomies and tetrasomies
      of chromosome 3q in bone marrow cells of 18 of 53 FA patients analyzed, detected
      by conventional and molecular cytogenetics. To determine the clinical relevance
      of these findings, we compared the cytogenetic data, the morphologic features of
      the bone marrow, and the clinical course of these patients with those of 35 FA
      patients without clonal aberrations of 3q. The 2 groups did not differ
      significantly with respect to age, sex, or complementation group. There was a
      significant survival advantage of patients without abnormalities of chromosome
      3q. Even more pronounced was the risk assessment of patients with gains of 3q
      material with respect to the development of morphologic MDS and acute myeloid
      leukemia (AML). Thus, our data from 18 patients with 3q aberrations reveal that
      gains of 3q are strongly associated with a poor prognosis and represent an
      adverse risk factor in FA.

PMID- 12511407
TI  - Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic
      stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1.
AB  - Complement has recently been implicated in developmental pathways and
      noninflammatory processes. The expression of various complement components and
      receptors has been shown in a wide range of circulating myeloid and lymphoid
      cells, but their role in normal hematopoiesis and stem cell homing has not yet
      been investigated. We report that normal human CD34(+) cells and lineage
      differentiated hematopoietic progenitors express the complement anaphylatoxin C3a
      receptor (C3aR) and respond to C3a. Moreover, C3a, but not the biologically
      inactive desArg-C3a, induces calcium flux in these cells. Furthermore, we found
      that C3 is secreted by bone marrow stroma and that, although C3a does not
      influence directly the proliferation/survival of hematopoietic progenitors, it
      (1) potentiates the stromal cell-derived factor 1 (SDF-1)-dependent chemotaxis of
      human CD34(+) cells and lineage-committed myeloid, erythroid, and megakaryocytic
      progenitors; (2) primes SDF-1-dependent trans-Matrigel migration; and (3)
      stimulates matrix metalloproteinase-9 secretion and very late antigen 4 (VLA-4)
      mediated adhesion to vascular cell adhesion molecule 1 (VCAM-1). Furthermore, we
      found that murine Sca-1(+) cells primed by C3a engrafted faster in lethally
      irradiated animals. These results indicate that normal human hematopoietic stem
      and progenitor cells express functional C3aR and that the C3aR-C3a axis
      sensitizes the responses of these cells to SDF-1 and thus may be involved in
      promoting their homing into the bone marrow via cross talk with the SDF-CXC
      chemokine receptor-4 (CXCR4) signaling axis. C3a is the first positive regulator
      of this axis to be identified.

PMID- 12511408
TI  - Prenatal diagnosis for congenital afibrinogenemia caused by a novel nonsense
      mutation in the FGB gene in a Palestinian family.
AB  - Congenital afibrinogenemia is a rare autosomal recessive disorder characterized
      by the complete absence of detectable fibrinogen. We previously identified the
      first causative mutations for this disease, homozygous deletions of approximately
      11 kb of the fibrinogen alpha chain gene (FGA). Subsequent analyses revealed that
      most afibrinogenemia alleles are truncating mutations of FGA, although mutations
      in all 3 fibrinogen genes, FGG, FGA and FGB have been identified. In this study,
      we performed the first prenatal diagnosis for afibrinogenemia. The causative
      mutation in a Palestinian family was a novel nonsense mutation in the FGB gene,
      Trp467Stop (W467X). Expression of the Trp467Stop mutant FGB cDNA in combination
      with wild-type FGA and FGG cDNAs showed that fibrinogen molecules containing the
      mutant beta chain are not secreted into the media. The fetus was found to be
      heterozygous for the Trp467Stop mutation by direct sequencing and by linkage
      analysis, a result that was confirmed in the newborn by intermediate fibrinogen
      levels.

PMID- 12511409
TI  - Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for
      plasmacytoid dendritic cells in adaptive immunity.
AB  - Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immune
      responses by producing type I interferons (IFNs) upon exposure to enveloped
      viruses. However, their role in adaptive immune responses, such as the initiation
      of antiviral T-cell responses, is not known. In this study, we examined
      interactions between blood pDCs and influenza virus with special attention to the
      capacity of pDCs to activate influenza-specific T cells. pDCs were compared with
      CD11c(+) DCs, the most potent antigen-presenting cells (APCs), for their capacity
      to activate T-cell responses. We found that like CD11c(+) DCs, pDCs mature
      following exposure to influenza virus, express CCR7, and produce proinflammatory
      chemokines, but differ in that they produce type I IFN and are resistant to the
      cytopathic effect of the infection. After influenza virus exposure, both DC types
      exhibited an equivalent efficiency to expand anti-influenza virus cytotoxic T
      lymphocytes (CTLs) and T helper 1 (TH1) CD4(+) T cells. Our results pinpoint a
      new role of pDCs in the induction of antiviral T-cell responses and suggest that
      these DCs play a prominent role in the adaptive immune response against viruses.

PMID- 12511410
TI  - Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation.
AB  - Interleukin-25 (IL-25) is a recently described T helper 2 (T(H)2) cell-derived
      cytokine that belongs to the IL-17 family and induces the production of IL-4, IL
      5, and IL-13 from an unidentified non-T-cell population. Here, we show that mast
      cells are also potent IL-25-producing cells. When bone marrow-derived mast cells
      were stimulated by immunoglobulin E cross-linking, IL-25 mRNA was induced within
      30 minutes in a calcineurin-dependent manner, and the levels of IL-25 mRNA were
      comparable with those of activated T(H)2 cells. Production of IL-25 by mast cells
      was also detected at protein levels by immunoblotting. These results suggest that
      mast cells may enhance T(H)2-type immune response by producing IL-25.

PMID- 12511411
TI  - Modified myeloid dendritic cells act as regulatory dendritic cells to induce
      anergic and regulatory T cells.
AB  - To exploit a novel strategy to regulate T cell-mediated immunity, we established
      human and murine modified dendritic cells (DCs) with potent immunoregulatory
      properties (designed as regulatory DCs), which displayed moderately high
      expression levels of major histocompatibility complex (MHC) molecules and
      extremely low levels of costimulatory molecules compared with their normal
      counterparts. Unlike human normal DCs, which caused the activation of allogeneic
      CD4(+) and CD8(+) T cells, human regulatory DCs not only induced their anergic
      state but also generated CD4(+) or CD8(+) regulatory T (Tr) cells from their
      respective naive subsets in vitro. Although murine normal DCs activated human
      xenoreactive T cells in vitro, murine regulatory DCs induced their
      hyporesponsiveness. Furthermore, transplantation of the primed human T cells with
      murine normal DCs into severe combined immunodeficient (SCID) mice enhanced the
      lethality caused by xenogeneic graft-versus-host disease (XGVHD), whereas
      transplantation of the primed human T cells with murine regulatory DCs impaired
      their ability to cause XGVHD. In addition, a single injection of murine
      regulatory DCs following xenogeneic or allogeneic transplantation protected the
      recipients from the lethality caused by XGVHD as well as allogeneic acute GVHD.
      Thus, the modulation of T cell-mediated immunity by regulatory DCs provides a
      novel therapeutic approach for immunopathogenic diseases.

PMID- 12511412
TI  - Anti-CD22 ligand-blocking antibody HB22.7 has independent lymphomacidal
      properties and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma
      xenografts.
AB  - CD22 is a membrane glycophosphoprotein found on nearly all healthy B-lymphocytes
      and most B-cell lymphomas. Recent in vitro studies have identified several anti
      CD22 monoclonal antibodies (mAbs) that block the interaction of CD22 with its
      ligand. One of these mAbs, HB22.7, has been shown to effectively induce apoptosis
      in several B-cell lymphoma cell lines. Lymphoma xenograft studies with Raji
      xenograft mice were used to assess the toxicity and efficacy of HB22.7 alone and
      with combined modality immunotherapy (CMIT) with yttrium (90)Y-DOTA-peptide-Lym-1
      radioimmunotherapy (RIT). The effect of the sequence of these agents on the
      combined treatment was assessed by administering HB22.7 24 hours before,
      simultaneously with, or 24 hours after RIT. Within the groups treated with RIT
      alone or with RIT and HB22.7 (CMIT), the reduction in tumor volume was the
      greatest when HB22.7 was administered simultaneously with and 24 hours after RIT,
      and in the RIT treatment groups, this translated into the greatest overall
      response and survival, respectively. Overall survival rates at the end of the 84
      day CMIT trial were 67% and 50% in the groups treated with HB22.7 simultaneously
      and 24 hours after RIT, respectively. This compared favorably with the untreated
      and the RIT alone groups, which had survival rates of 38% and 43% at the end of
      the trial. Surprisingly, when compared with untreated controls and all other
      treatment groups, the greatest cure and overall survival rates were observed in
      the group treated with HB22.7 alone, with 47% cured and 76% surviving at the end
      of the 84-day trial. RIT clearance was not affected by treatment with HB22.7.
      When compared with RIT alone, there was no significant additional hematologic
      (white blood cell, red blood cell, or platelet count) toxicity when HB22.7 was
      added to RIT. Nonhematologic toxicity (assessed as change in body weight) was
      also unchanged when HB22.7 was added to RIT. Thus the anti-CD22 ligand-blocking
      antibody HB22.7 has independent lymphomacidal properties and augments the
      efficacy of (90)Y-DOTA-peptide-Lym-1 in lymphoma xenografts without significant
      toxicity.

PMID- 12511413
TI  - Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress
      differentiation into osteoclasts but not into macrophages.
AB  - Histone deacetylase (HDAC) inhibitors are emerging as a new class of anticancer
      therapeutic agents and have been demonstrated to induce differentiation in some
      myeloid leukemia cell lines. In this study, we show that HDAC inhibitors have a
      novel action on osteoclast differentiation. The effect of 2 HDAC inhibitors,
      trichostatin A (TSA) and sodium butyrate (NaB), on osteoclastogenesis was
      investigated using rat and mouse bone marrow cultures and a murine macrophage
      cell line RAW264. Both TSA and NaB inhibited the formation of preosteoclast-like
      cells (POCs) and multinucleated osteoclast-like cells (MNCs) in rat bone marrow
      culture. By reverse transcription-polymerase chain reaction analysis, TSA reduced
      osteoclast-specific mRNA expression of cathepsin K and calcitonin receptor (CTR).
      In contrast, TSA and NaB did not affect the formation of bone marrow macrophages
      (BMMs) induced by macrophage colony-stimulating factor as examined by nonspecific
      esterase staining. Fluorescence-activated cell sorting analysis showed that TSA
      did not affect the surface expression of macrophage markers for CD11b and F4/80
      of BMMs. TSA and NaB also inhibited osteoclast formation and osteoclast-specific
      mRNA expression in RAW264 cells stimulated with receptor activator of nuclear
      factor-kappa B (NF-kappa B) ligand (RANKL). Transient transfection assay revealed
      that TSA and NaB dose dependently reduced the sRANKL-stimulated or tumor necrosis
      factor alpha (TNF-alpha)-stimulated transactivation of NF-kappa B-dependent
      reporter genes. The treatment of RAW264 cells with TSA and NaB inhibited TNF
      alpha-induced nuclear translocation of NF-kappa B and sRANKL-induced activation
      of p38 mitogen-activated protein kinase (MAPK) signals. These data suggest that
      both TSA and NaB exert their inhibitory effects by modulating osteoclast-specific
      signals and that HDAC activity regulates the process of osteoclastogenesis.

PMID- 12511414
TI  - Gains of 2p involving the REL locus correlate with nuclear c-Rel protein
      accumulation in neoplastic cells of classical Hodgkin lymphoma.
AB  - Structural aberrations of the short arm of chromosome 2, mostly resulting in
      gains of 2p13 approximately 16, have recently been described as being highly
      recurrent in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma
      (cHL). As these gains consistently lead to increased copy numbers of the REL
      oncogene locus, we investigated the expression of the c-Rel protein in a series
      of 30 cHL cases with known genomic REL status as determined by comparative
      genomic hybridization and interphase cytogenetics. Expression of the c-Rel
      protein was investigated in 26 biopsies by immunohistochemistry. Distinct
      patterns were observed in HRS cells with no staining, cytoplasmic, and/or nuclear
      staining for c-Rel. All 13 samples with additional copies of the REL locus
      displayed nuclear staining for c-Rel, while 13 cHL samples lacking chromosome 2
      (2p) gains displayed a significantly lower proportion or complete absence of HRS
      cells with nuclear c-Rel expression. Detailed analysis using combined
      immunophenotyping and interphase cytogenetics of individual HRS cells
      demonstrated that REL gains correlated with the presence of nuclear c-Rel
      staining. Additionally, in 2 cHL samples with translocation breakpoints in 2p13
      approximately 16, nuclear staining of c-Rel was observed; in one of them the
      staining pattern was indicative of a truncated c-Rel protein. The correlation
      between structural aberrations involving the REL locus and nuclear c-Rel
      accumulation in HRS cells qualifies REL as a target gene of the frequent gains in
      2p in cHL. The data suggest that REL aberrations are a genetic mechanism
      contributing to constitutive nuclear factor (NF)-kappa B/Rel activation in cHL.

PMID- 12511415
TI  - Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic
      cell transplantation.
AB  - Interactions between killer immunoglobulin-like receptors (KIRs) and human
      leukocyte antigen (HLA) class I ligands influence development of natural killer
      (NK) cell repertoire and response to infection, cancer, and allogeneic tissue. As
      KIRs and HLA class I molecules are highly polymorphic, clinical allogeneic
      hematopoietic cell transplantation is predicted to frequently involve KIR
      mismatch, and thus to provide a unique system for study of human NK cell receptor
      repertoire development. Eighteen leukemia patients undergoing HLA-matched
      transplantation and their donors were analyzed for KIR genotype. Ten of 13 HLA
      identical donor-patient pairs were KIR mismatched and 3 were matched; all HLA
      matched unrelated pairs were KIR mismatched. Reconstitution of recipient NK cell
      repertoire following transplantation was examined using flow cytometry and
      monoclonal antibodies specific for KIR and CD94:NKG2A. These data form 3 groups.
      Six to 9 months after transplantation, 8 patients (group 1) reconstituted an NK
      cell repertoire resembling that of their donor, and for KIR-mismatched
      transplants, distinct from the recipient before transplantation. In the first
      year after transplantation, 5 patients (group 2) exhibited a generally depressed
      frequency of KIR-expressing NK cells and concomitant high frequency of CD94:NKG2A
      expression. By 3 years after transplantation, the frequency of KIR-expressing NK
      cells had increased to donor values, in the 3 patients from group 2 analyzed for
      this period. The remaining 5 patients experienced severe clinical complications
      following transplantation and displayed unique features in their NK cell receptor
      reconstitution. These results demonstrate that a majority of HLA-matched
      hematopoietic cell transplantations involve KIR mismatch and reveal differences
      in NK cell repertoire having potential impact for immune responsiveness and
      transplantation outcome.

PMID- 12511416
TI  - Acceleration of idiopathic pneumonia syndrome (IPS) in the absence of donor MIP-1
      alpha (CCL3) after allogeneic BMT in mice.
AB  - Idiopathic pneumonia syndrome (IPS) is a significant cause of morbidity and
      mortality after bone marrow transplantation (BMT) in humans. We developed a
      murine IPS model in which lethal pre-BMT conditioning and allogeneic T cells
      results in the recruitment of host monocytes and then donor T cells into the lung
      by day 7 after BMT, concomitant with development of severe lung dysfunction. We
      reported the T cell-dependent production of the T cell-attracting chemokine
      macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the lungs of such
      recipient mice. We reasoned that MIP-1 alpha might be a critical mediator of IPS.
      Lethally conditioned mice received transplants of major histocompatibility
      complex-disparate marrow and either wild-type (MIP-1 alpha(+/+)) or knockout (MIP
      1 alpha(-/-)) spleen cells. Recipients of MIP-1 alpha(-/-) cells exhibited
      accelerated mortality and a decrease in specific compliance that appeared earlier
      than in recipients of MIP-1 alpha(+/+) cells. Donor CD4(+) and CD8(+) T cell
      expansion was increased in the spleens of recipients of MIP-1 alpha(-/-) cells.
      Lungs of recipients of MIP-1 alpha(-/-) cells had earlier recruitment of both T
      cell subsets by day 3 after BMT, concomitant with the influx of cells expressing
      the cytolysins granzymes A and B. Monocyte recruitment was not altered. Levels of
      inflammatory cytokines were not increased and levels of T cell-attracting
      chemokines were decreased. The level of the anti-inflammatory cytokine
      interleukin 13 (IL-13) was lower in the serum and lungs of recipients of MIP-1
      alpha(-/-) cells, indicating a skewing toward a more inflammatory T helper cell
      type 1 (Th1) cytokine milieu. Donor-derived MIP-1 alpha may play a role in
      allogeneic-induced IPS by limiting aggressive expansion of CD4(+) and CD8(+) T
      cells.

PMID- 12511417
TI  - Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin
      lymphomas.
AB  - Activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM),
      class switch recombination (CSR), and immunoglobulin gene conversion in B
      lymphocytes. Here we report for the first time the expression of AID in healthy
      human B-lymphocytes and in B-cell non-Hodgkin lymphomas (B-NHL). AID mRNA
      expression in humans is restricted to the CD19(+)CD38(+)IgD(-) germinal center
      cells, namely the CD19(+)CD38(+)CD44(-) centroblasts. After in vitro stimulation
      of naive human B cells by CD40-L and IL-4, AID mRNA is strongly induced for only
      48 hours. In a survey of human B-NHL AID was found to be constitutively expressed
      in follicular lymphoma and in diffuse large B-cell lymphoma but to be absent in B
      precursor lymphoblastic leukemia, in mantle cell lymphoma, and in plasma cell
      myeloma. In B-cell chronic lymphatic leukemia, in immunocytoma, and in extranodal
      marginal zone B-cell lymphoma of MALT, AID mRNA was expressed only in some
      samples. In follicular lymphoma and diffuse large B-cell lymphoma, the expression
      of AID mRNA was coincident with the presence of SHM in the variable region exons
      of the immunoglobulin heavy-chain gene. In human B-NHL, the AID mRNA is spliced
      into 4 different variants but does not contain point mutations. Thus AID, which
      is highly regulated during healthy B-cell development, is constitutively
      expressed in human germinal center B-NHL and in subsets of nongerminal center B
      NHL. This constitutive expression of AID may promote illegitimate DNA
      recombinations and somatic mutations in B-NHL.

PMID- 12511418
TI  - Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone
      analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart
      cells.
AB  - Although iron chelation therapy with deferoxamine (DFO) results in improved life
      expectancy of patients with thalassemia, compliance with parenteral DFO treatment
      is unsatisfactory, underlining the need for alternative drugs and innovative ways
      of drug administration. We examined the chelating potential of pyridoxal
      isonicotinoyl hydrazone (PIH) analogs, alone or in combination with DFO, using
      hypertransfused rats with labeled hepatocellular iron stores and cultured iron
      loaded rat heart cells. Our in vivo studies using 2 representative PIH analogs,
      108-o and 109-o, have shown that PIH analogs given orally are 2.6 to 2.8 times
      more effective in mobilizing hepatocellular iron in rats, on a weight-per-weight
      basis, than parenteral DFO administered intraperitoneally. The combined effect of
      DFO and 108-o on hepatocellular iron excretion was additive, and response at a
      dose range of 25 to 200 mg/kg was linear. In vitro studies in heart cells showed
      that DFO was more effective in heart cell iron mobilization than all PIH analogs
      studied. Response to joint chelation with DFO and PIH analogs was similar to an
      increase in the equivalent molar dose of DFO alone, rather than the sum of the
      separate effects of the PIH analog and DFO. This finding was most likely the
      result of iron transfer from PIH analogs to DFO, a conclusion supported directly
      by iron-shuttle experiments using fluorescent DFO. These findings provide a
      rationale for the combined, simultaneous use of iron-chelating drugs and may have
      useful, practical implications for designing novel strategies of iron chelation
      therapy.

PMID- 12511419
TI  - Side effects of retroviral gene transfer into hematopoietic stem cells.
AB  - Recent conceptual and technical improvements have resulted in clinically
      meaningful levels of gene transfer into repopulating hematopoietic stem cells. At
      the same time, evidence is accumulating that gene therapy may induce several
      kinds of unexpected side effects, based on preclinical and clinical data. To
      assess the therapeutic potential of genetic interventions in hematopoietic cells,
      it will be important to derive a classification of side effects, to obtain
      insights into their underlying mechanisms, and to use rigorous statistical
      approaches in comparing data. We here review side effects related to target cell
      manipulation; vector production; transgene insertion and expression; selection
      procedures for transgenic cells; and immune surveillance. We also address some
      inherent differences between hematopoiesis in the most commonly used animal
      model, the laboratory mouse, and in humans. It is our intention to emphasize the
      need for a critical and hypothesis-driven analysis of "transgene toxicology," in
      order to improve safety, efficiency, and prognosis for the yet small but
      expanding group of patients that could benefit from gene therapy.

PMID- 12511420
TI  - Nonmalignant late effects after allogeneic stem cell transplantation.

PMID- 12511421
TI  - Rosmarinic acid inhibits Ca2+-dependent pathways of T-cell antigen receptor
      mediated signaling by inhibiting the PLC-gamma 1 and Itk activity.
AB  - Rosmarinic acid (RosA) is a hydroxylated compound frequently found in herbal
      plants and is mostly responsible for anti-inflammatory and antioxidative
      activity. Previously, we observed that RosA inhibited T-cell antigen receptor
      (TCR)- induced interleukin 2 (IL-2) expression and subsequent T-cell
      proliferation in vitro. In this study, we investigated in detail inhibitory
      mechanism of RosA on TCR signaling, which ultimately activates IL-2 promoter by
      activating transcription factors, such as nuclear factor of activated T cells (NF
      AT) and activating protein-1 (AP-1). Interestingly, RosA inhibited NF-AT
      activation but not AP-1, suggesting that RosA inhibits Ca(2+)-dependent signaling
      pathways only. Signaling events upstream of NF-AT activation, such as the
      generation of inositol 1,4,5-triphosphate and Ca(2+) mobilization, and tyrosine
      phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) were strongly inhibited
      by RosA. Tyrosine phosphorylation of PLC-gamma 1 is largely dependent on 3 kinds
      of protein tyrosine kinases (PTKs), ie, Lck, ZAP-70, and Itk. We found that RosA
      efficiently inhibited TCR-induced tyrosine phosphorylation and subsequent
      activation of Itk but did not inhibit Lck or ZAP-70. ZAP-70-dependent signaling
      pathways such as the tyrosine phosphorylation of LAT and SLP-76 and
      serine/threonine phosphorylation of mitogen-activated protein kinases (MAPKs)
      were intact in the presence of RosA, confirming that RosA suppresses TCR
      signaling in a ZAP-70-independent manner. Therefore, we conclude that RosA
      inhibits TCR signaling leading to Ca(2+) mobilization and NF-AT activation by
      blocking membrane-proximal events, specifically, the tyrosine phosphorylation of
      inducible T cells kinase (Itk) and PLC-gamma 1.

PMID- 12511422
TI  - BCR/ABL alters the function of NK cells and the acquisition of killer
      immunoglobulin-like receptors (KIRs).
AB  - Natural killer (NK) cells decrease in function during chronic myelogenous
      leukemia (CML) progression from chronic phase to blast crisis, and they can
      become BCR/ABL(+) late in the disease course. To study this altered function,
      NK92 cells were transduced with the BCR/ABL oncogene. In contrast to the parental
      cells, which died when deprived of interleukin 2 (IL-2), p210(+) NK92 cells
      proliferated and survived indefinitely in the absence of IL-2. BCR/ABL also
      decreased the natural cytotoxicity of NK92 cells against K562 targets, without
      affecting IL-2, interferon gamma (IFN-gamma), or tumor necrosis factor alpha (TNF
      alpha) production. Although the ABL-specific tyrosine kinase inhibitor imatinib
      mesylate (STI-571) had no effect on parental NK92 cells, it markedly decreased
      the growth and survival of IL-2-independent p210(+) NK92 cells. In contrast to
      the parental cell line, serial analysis of p210(+) NK92 cells detected small
      populations that clonally expressed one or more killer immunoglobulin-like
      receptors (KIRs). Unlike the decreased natural cytotoxicity, the function of the
      activating CD158j receptor remained intact. Southern blotting and hybridization
      with an enhanced green fluorescence protein (eGFP) probe showed that KIR(-) and
      KIR(+) NK92 cells were all derived from the same clone, suggesting that KIR
      acquisition remains dynamic at the maturational stage represented by the NK92
      cell line. When tested in primary CD56(+bright) NK cells, p210 induced partial IL
      2-independent growth and increased KIR expression similar to findings in NK92
      cells. This is the first study to show that BCR/ABL, well known for its effects
      on the myeloid lineage, can alter the function of lymphoid cells, which may be
      associated with the defect in innate immunity associated with CML progression.

PMID- 12511423
TI  - Specific transgene expression in human and mouse CD4+ cells using lentiviral
      vectors with regulatory sequences from the CD4 gene.
AB  - Achieving cell-specific expression of a therapeutic transgene by gene transfer
      vectors represents a major goal for gene therapy. To achieve specific expression
      of a transgene in CD4(+) cells, we have generated lentiviral vectors expressing
      the enhanced green fluorescent protein (eGFP) reporter gene under the control of
      regulatory sequences derived from the CD4 gene--a minimal promoter and the
      proximal enhancer, with or without the silencer. Both lentiviral vectors could be
      produced at high titers (more than 10(7) infectious particles per milliliter) and
      were used to transduce healthy murine hematopoietic stem cells (HSCs). On
      reconstitution of RAG-2-deficient mice with transduced HSCs, the specific vectors
      were efficiently expressed in T cells, minimally expressed in B cells, and not
      expressed in immature cells of the bone marrow. Addition of the CD4 gene
      silencing element in the vector regulatory sequences led to further restriction
      of eGFP expression into CD4(+) T cells in reconstituted mice and in ex vivo
      transduced human T cells. Non-T CD4(+) dendritic and macrophage cells derived
      from human CD34(+) cells in vitro expressed the transgene of the specific
      vectors, albeit at lower levels than CD4(+) T cells. Altogether, we have
      generated lentiviral vectors that allow specific targeting of transgene
      expression to CD4(+) cells after differentiation of transduced mice HSCs and
      human mature T cells. Ultimately, these vectors may prove useful for in situ
      injections for in vivo gene therapy of HIV infection or genetic
      immunodeficiencies.

PMID- 12511424
TI  - Missense mutation and defective function of ATM in a childhood acute leukemia
      patient with MLL gene rearrangement.
AB  - The possible involvement of germline mutation of the ataxia telangiectasia
      mutated (ATM) gene in childhood acute leukemia with mixed lineage leukemia (MLL)
      gene rearrangement (MLL(+)) was investigated. Of the 7 patients studied, 1 showed
      a germline missense ATM mutation (8921C>T; Pro2974Leu), located in the
      phosphatidylinositol-3 (PI-3) kinase domain. In reconstitution assays, the ATM
      mutant 8921T could only partially rescue the radiosensitive phenotype of AT
      fibroblasts, and in an in vitro kinase assay, it showed a defective
      phosphorylation of p53-Ser15. Furthermore, the introduction of 8921T in U2OS
      cells, characterized by a normal ATM/p53 signal transduction, caused a
      significant reduction of in vivo p53-Ser15 phosphorylation, suggesting a dominant
      negative effect of the mutant ATM over the wild-type protein. Our finding in this
      patient suggests that altered function of ATM plays some pathogenic roles in the
      development of MLL(+) leukemia.

PMID- 12511425
TI  - Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct
      intracellular granule mobilization toward ingested microbial pathogens.
AB  - Elevated levels of mitogen-activated protein kinase/extracellular regulatory
      kinase (MAPK/ERK) activity are frequently found in some cancer cells. In efforts
      to reduce tumor growth, attempts have been made to develop cancer therapeutic
      agents targeting the MAPK. Here, by use of biologic, biochemical, and gene
      manipulation methods in human polymorphonuclear neutrophils (PMNs), we have
      identified a key pathway important in normal cell function involving MAPK/ERK in
      PMNs for growth inhibition of Candida albicans. Contact with C albicans triggered
      MAPK/ERK activation in PMNs within 5 minutes, and blocking of MAPK/ERK
      activation, either by the pharmacologic reagent PD098059 or by dominant-negative
      MAPK kinase (MEK) expression via vaccinia viral delivery, suppressed
      antimicrobial activity. Rac and Cdc42, but not Ras or Rho, were responsible for
      this MAPK/ERK activation. Expression of dominant-negative Rac (N17Rac) or Cdc42
      (N17Cdc42) eliminated not only C albicans- mediated ERK phosphorylation but also
      phagocytosis and granule migration toward the ingested microbes, whereas dominant
      negative Ras (N17Ras) and Rho (N19Rho) did not. PAK1 (p21-activated kinase 1)
      activation is induced by C albicans, suggesting that PAK1 may also be involved in
      the Rac1 activation of MAPK/ERK. We conclude from these data that Rac/Cdc42
      dependent activation of MAPK/ERK is a critical event in the immediate phagocytic
      response of PMNs to microbial challenge. Therefore, use of MAPK pharmacologic
      inhibitors for the treatment of cancer may result in the interruption of normal
      neutrophil function. A balance between therapeutic outcome and undesirable side
      effects must be attained to achieve successful and safe anticancer therapy.

PMID- 12511426
TI  - Peripheral O2 chemoreceptors mediate humoral catecholamine secretion from fish
      chromaffin cells.
AB  - This study addressed the hypothesis that the secretion of catecholamines from
      trout (Oncorhynchus mykiss) chromaffin cells, during hypoxia, is triggered by
      stimulation of O(2) chemoreceptors located within the gills. Sodium cyanide was
      administered into the inspired water (external cyanide) or injected into the gill
      circulation (internal cyanide) to pharmacologically stimulate external (water
      sensing) or internal (blood sensing) O(2) chemoreceptors, respectively. Both of
      these treatments caused an elevation of circulating catecholamine levels. The
      response to external, but not internal, cyanide was abolished by removal of the
      first gill arch. Hypoxia produced an increase in circulating catecholamine levels
      that was unaffected by removal of the first gill arch or by denervation of the
      pseudobranch. Cyanide and hypoxia both caused the well-documented
      cardiorespiratory reflexes normally observed in this species. This study
      demonstrates, for the first time, that gill O(2) chemoreceptors can initiate the
      reflex that leads to catecholamine release from the chromaffin cells and that
      stimulation of internally oriented O(2) receptors on all gill arches appears to
      be the physiologically important mechanism for initiating release.

PMID- 12511427
TI  - Intracranial renin alters gustatory neural responses in the nucleus of the
      solitary tract of rats.
AB  - Activation of the renin-angiotensin system in the brain is considered important
      in the arousal and expression of sodium appetite. To clarify the effects of
      directly activating this hormonal cascade, taste neurons in the nucleus of the
      solitary tract of rats were tested with a battery of sapid stimuli after
      intracerebroventricular injection of renin or its vehicle. The rats were
      chronically prepared but lightly anesthetized during the recording procedure.
      Eighty-five taste neurons were tested: 46 after renin injections and 39 after
      vehicle. Neural activity was counted for 5.0-s periods without stimulation
      (spontaneous) and during stimulation with water and sapid chemicals. The averaged
      responses to each of the standard stimuli (0.1 M NaCl, 0.3 M sucrose, 0.01 M
      citric acid, and 0.01 M quinine hydrochloride) did not differ significantly
      between the two conditions. When the rats were tested with a concentration range
      of NaCl, however, after renin the average responses to the hypertonic 0.3 and 1.0
      M stimuli were reduced to 74 and 70%, respectively, compared with those after
      vehicle injections. A similar tendency was evident for the subsample of neurons
      that responded best to NaCl, but the effect was smaller. These data are
      consistent with, but not as dramatic as, those reported after dietary-induced
      sodium appetite.

PMID- 12511428
TI  - Coronary flow-induced inotropism is modulated by binding of dextrans to the
      endothelial luminal surface.
AB  - In isolated perfused guinea pig hearts, coronary flow causes a positive inotropic
      effect [positive coronary flow-induced effect (+CFIE)] that could be altered by
      dextrans (Dx) in the coronary perfusion solution. To test this possibility, Dx of
      20, 40, 70, and 500 kDa were infused and found to modulate +CFIE; however, when
      Dx infusion was terminated, the effect persisted, i.e., was
      irreversible/nonwashable, suggesting that Dx may bind to luminal endothelial
      lectinic structures. This hypothesis was tested when Dx [with fluorescent traces
      (D*)] bound to the vessel wall was hydrolyzed by dextranase infusion and washout
      of D* fragments completely reverted the +CFIE, and it was found that bound D* to
      be displaced by free Dx required concentrations 50-100 times that used during
      binding. In addition, dose-response curves for Dx on +CFIE show that the higher
      the Dx molecular mass, the lesser the concentration required to have an effect.
      Because a large Dx molecule has a greater number polymeric glucose branches, it
      can bind to a larger number of endothelial lectinic sites, requiring a lower
      concentration to affect +CFIE. Our results suggest that luminal endothelial
      lectinic structures are part of the flow-sensing assembly.

PMID- 12511429
TI  - Role of endothelial Ca2+ stores in the regulation of hydraulic conductivity of
      Rana microvessels in vivo.
AB  - Vascular permeability is regulated by endothelial cytosolic Ca(2+) concentration
      ([Ca(2+)](i)). To determine whether vascular permeability is dependent on
      extracellular Ca(2+) influx or release of Ca(2+) from stores, hydraulic
      conductivity (L(p)) was measured in single perfused frog mesenteric microvessels
      in the presence and absence of Ca(2+) influx and store depletion. Prevention of
      Ca(2+) reuptake into stores by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)
      inhibition increased L(p) in the absence of extracellular Ca(2+) influx. L(p) was
      further increased when Ca(2+) influx was restored. Depletion of the Ca(2+) stores
      with ionomycin and SERCA inhibition increased L(p) in the presence and the
      absence of extracellular Ca(2+) influx. However, store depletion in itself did
      not significantly increase L(p) in the absence of active Ca(2+) release from
      stores into the cytoplasm. There was a significant positive correlation between
      baseline permeability and the magnitude of the responses to both Ca(2+) store
      release and Ca(2+) influx, indicating that the Ca(2+) regulating properties of
      the endothelial cells may regulate the baseline L(p). To investigate the role of
      Ca(2+) stores in regulation of L(p), the relationship between SERCA inhibition
      and store release was studied. The magnitude of the L(p) increase during SERCA
      inhibition significantly and inversely correlated with that during store release
      by Ca(2+) ionophore, implying that the degree of store depletion regulates the
      size of the increase on L(p). These data show that microvascular permeability in
      vivo can be increased by agents that release Ca(2+) from stores in the absence of
      Ca(2+) influx. They also show that capacitative Ca(2+) entry results in increased
      L(p) and that the size of the permeability increase can be regulated by the
      degree of Ca(2+) release.

PMID- 12511430
TI  - Increased nitric oxide production following chronic hypoxia contributes to
      attenuated systemic vasoconstriction.
AB  - Attenuated vasoconstrictor reactivity following chronic hypoxia (CH) is
      associated with endothelium-dependent vascular smooth muscle (VSM) cell
      hyperpolarization and diminished intracellular [Ca(2+)]. We tested the hypothesis
      that increased production of nitric oxide (NO) after CH contributes to blunted
      vasoconstrictor responsiveness. We found that basal NO production of mesenteric
      arteries from CH rats (barometric pressure = 380 Torr; 48 h) was greater than
      that of controls (barometric pressure = 630 Torr). In addition, studies employing
      pressurized mesenteric arteries (100-200 microM ID) abluminally loaded with the
      Ca(2+) indicator fura 2-AM demonstrated that although NO synthase (NOS)
      inhibition normalized agonist-induced vasoconstrictor responses between groups,
      VSM cell [Ca(2+)] in vessels from CH rats remained diminished compared with
      controls. To determine whether elevated NO production following CH results from
      increased NOS protein levels, we performed Western blots for NOS isoforms by
      using mesenteric arteries from control and CH rats. Endothelial NOS levels did
      not differ between groups, and other NOS isoforms were not detected in these
      samples. Selective endothelial loading of fura 2-AM was employed to test the
      hypothesis that elevated endothelial cell [Ca(2+)] following CH accounts for
      enhanced NOS activity. These experiments demonstrated greater endothelial cell
      [Ca(2+)] in mesenteric arteries isolated from CH rats compared with controls. We
      conclude that enhanced production of NO resulting from elevated endothelial cell
      [Ca(2+)] contributes to attenuated reactivity following CH by decreasing VSM cell
      Ca(2+) sensitivity.

PMID- 12511431
TI  - Breast self examination.

PMID- 12511432
TI  - Using clinical databases in practice.

PMID- 12511433
TI  - Reporting diagnostic tests.

PMID- 12511434
TI  - Contraindications to the use of metformin.

PMID- 12511435
TI  - Evidence based policy making.

PMID- 12511437
TI  - Family finds hospital willing to give experimental CJD treatment.

PMID- 12511439
TI  - US blocks deal on cheap drugs.

PMID- 12511444
TI  - Health care is among the most corrupt services in India.

PMID- 12511446
TI  - "Free" medical publishing venture gets under way.

PMID- 12511447
TI  - EU sets standards for safe blood products.

PMID- 12511448
TI  - German hospital curtails services because of deficit.

PMID- 12511452
TI  - Analgesic effect of breast feeding in term neonates: randomised controlled trial.
AB  - OBJECTIVES: To investigate whether breast feeding is effective for pain relief
      during venepuncture in term neonates and compare any effect with that of oral
      glucose combined with a pacifier. DESIGN: Randomised controlled trial.
      PARTICIPANTS: 180 term newborn infants undergoing venepuncture; 45 in each group.
      INTERVENTIONS: During venepuncture infants were either breast fed (group 1), held
      in their mother's arms without breast feeding (group 2), given 1 ml of sterile
      water as placebo (group 3), or given 1 ml of 30% glucose followed by pacifier
      (group 4). Video recordings of the procedure were assessed by two observers
      blinded to the purpose of the study. MAIN OUTCOME MEASURES: Pain related
      behaviours evaluated with two acute pain rating scales: the Douleur Aigue Nouveau
      ne scale (range 0 to 10) and the premature infant pain profile scale (range 0 to
      18). RESULTS: Median pain scores (interquartile range) for breast feeding, held
      in mother's arms, placebo, and 30% glucose plus pacifier groups were 1 (0-3), 10
      (8.5-10), 10 (7.5-10), and 3 (0-5) with the Douleur Aigue Nouveau-ne scale and
      4.5 (2.25-8), 13 (10.5-15), 12 (9-13), and 4 (1-6) with the premature infant pain
      profile scale. Analysis of variance showed significantly different median pain
      scores (P<0.0001) among the groups. There were significant reductions in both
      scores for the breast feeding and glucose plus pacifier groups compared with the
      other two groups (P<0.0001, two tailed Mann-Whitney U tests between groups). The
      difference in Douleur Aigue Nouveau-ne scores between breast feeding and glucose
      plus pacifier groups was not significant (P=0.16). CONCLUSIONS: Breast feeding
      effectively reduces response to pain during minor invasive procedure in term
      neonates.

PMID- 12511453
TI  - Sexual behaviour of adolescents in Nigeria: cross sectional survey of secondary
      school students.
AB  - OBJECTIVES: To determine whether family structure (polygamous or monogamous) is
      associated with sexual activity among school students in Nigeria. DESIGN: Cross
      sectional school survey with a two stage, clustered sampling design.
      PARTICIPANTS: 4218 students aged 12-21 years attending 39 schools in Plateau
      state, Nigeria. Responses from 2705 students were included in the analysis. MAIN
      OUTCOME MEASURE: Report of ever having had sexual intercourse. Variables of
      interest included sexual history, age, sex, religion, family polygamy,
      educational level of parents, having a dead parent, and sense of connectedness to
      parents and school. RESULTS: Overall 909 students (34%) reported ever having had
      sexual intercourse, and 1119 (41%) reported a polygamous family structure. Sexual
      activity was more common among students from polygamous families (42% of
      students) than monogamous families (28%) (chi2=64.23; P<0.0001). Variables
      independently associated with sexual activity were male sex (adjusted odds ratio
      2.52 (95% confidence interval 2.05 to 3.12)), older age (1.62 (1.24 to 2.14)),
      lower sense of connectedness with parents (1.87 (1.48 to 2.38)), having a dead
      parent (1.59 (1.27 to 2.00)), family polygamy (1.58 (1.29 to 1.92)), lower sense
      of connectedness with school (1.25 (1.09 to 1.44)), and lower educational level
      of parents (1.14 (1.05 to 1.24)). Multistep logistic regression analysis showed
      that the effect of polygamy on sexual activity was reduced by 27% by whether
      students were married and 22% by a history of forced sex. CONCLUSIONS: Secondary
      school students in Nigeria from a polygamous family structure are more likely to
      have engaged in sexual activity than students from a monogamous family structure.
      This effect is partly explained by a higher likelihood of marriage during
      adolescence and forced sex. Students' sense of connectedness to their parents and
      school, regardless of family structure, decreases the likelihood of sexual
      activity, and fostering this sense may help reduce risky sexual behaviour among
      Nigerian youth.

PMID- 12511454
TI  - Parental diabetes and birth weight of offspring: intergenerational cohort study.

PMID- 12511455
TI  - Incidence of coronary heart disease in a health authority in London: review of a
      community register.

PMID- 12511456
TI  - Syncope, driving recommendations, and clinical reality: survey of patients.

PMID- 12511457
TI  - National survey of job satisfaction and retirement intentions among general
      practitioners in England.
AB  - OBJECTIVES: To measure general practitioners' intentions to quit direct patient
      care, to assess changes between 1998 and 2000, and to investigate associated
      factors, notably job satisfaction. DESIGN: Analysis of national postal surveys
      conducted in 1998 and 2001. SETTING: England. PARTICIPANTS: 1949 general
      practitioner principals, of whom 790 were surveyed in 1998 and 1159 in 2001. MAIN
      OUTCOME MEASURES: Overall job satisfaction and likelihood of leaving direct
      patient care in the next five years. RESULTS: The proportion of doctors intending
      to quit direct patient care in the next five years rose from 14% in 1998 to 22%
      in 2001. In both years, the main factors associated with an increased likelihood
      of quitting were older age and ethnic minority status. Higher job satisfaction
      and having children younger than 18 years were associated with a reduced
      likelihood of quitting. There were no significant differences in regression
      coefficients between 1998 and 2001, suggesting that the effect of factors
      influencing intentions to quit remained stable over time. The rise in intentions
      to quit was due mainly to a reduction in job satisfaction (1998 mean 4.64, 2001
      mean 3.96) together with a slight increase in the proportion of doctors from
      ethnic minorities and in the mean age of doctors. Doctors' personal and practice
      characteristics explained little of the variation in job satisfaction within or
      between years. CONCLUSIONS: Job satisfaction is an important factor underlying
      intention to quit, and attention to this aspect of doctors' working lives may
      help to increase the supply of general practitioners.

PMID- 12511458
TI  - How to evaluate and improve the quality and credibility of an outcomes database:
      validation and feedback study on the UK Cardiac Surgery Experience.
AB  - OBJECTIVES: To assess the quality and completeness of a database of clinical
      outcomes after cardiac surgery and to determine whether a process of validation,
      monitoring, and feedback could improve the quality of the database. DESIGN:
      Stratified sampling of retrospective data followed by prospective re-sampling of
      database after intervention of monitoring, validation, and feedback. SETTING: Ten
      tertiary care cardiac surgery centres in the United Kingdom. INTERVENTION:
      Validation of data derived from a stratified sample of case notes (recording of
      deaths cross checked with mortuary records), monitoring of completeness and
      accuracy of data entry, feedback to local data managers and lead surgeons. MAIN
      OUTCOME MEASURES: Average percentage missing data, average kappa coefficient, and
      reliability score by centre for 17 variables required for assignment of risk
      scores. Actual minus risk adjusted mortality in each centre. RESULTS: The
      database was incomplete, with a mean (SE) of 24.96% (0.09%) of essential data
      elements missing, whereas only 1.18% (0.06%) were missing in the patient records
      (P<0.0001). Intervention was associated with (a) significantly less missing data
      (9.33% (0.08%) P<0.0001); (b) marginal improvement in reliability of data and
      mean (SE) overall centre reliability score (0.53 (0.15) v 0.44 (0.17)); and (c)
      improved accuracy of assigned Parsonnet risk scores (kappa 0.84 v 0.70).
      Mortality scores (actual minus risk adjusted mortality) for all participating
      centres fell within two standard deviations of the mean score. CONCLUSION: A
      short period of independent validation, monitoring, and feedback improved the
      quality of an outcomes database and improved the process of risk adjustment, but
      with substantial room for further improvement. Wider application of this approach
      should increase the credibility of similar databases before their public release.

PMID- 12511459
TI  - A web-based system for individualised survival estimation in breast cancer.

PMID- 12511460
TI  - Care of the dying patient: the last hours or days of life.

PMID- 12511461
TI  - Danger of salt substitutes that contain potassium in patients with renal failure.

PMID- 12511462
TI  - Antithrombotic therapy in special circumstances. I--pregnancy and cancer.

PMID- 12511463
TI  - Towards complete and accurate reporting of studies of diagnostic accuracy: the
      STARD initiative.
AB  - OBJECTIVE: To improve the accuracy and completeness of reporting of studies of
      diagnostic accuracy, to allow readers to assess the potential for bias in a
      study, and to evaluate a study's generalisability. METHODS: The Standards for
      Reporting of Diagnostic Accuracy (STARD) steering committee searched the
      literature to identify publications on the appropriate conduct and reporting of
      diagnostic studies and extracted potential items into an extensive list.
      Researchers, editors, and members of professional organisations shortened this
      list during a two day consensus meeting, with the goal of developing a checklist
      and a generic flow diagram for studies of diagnostic accuracy. RESULTS: The
      search for published guidelines about diagnostic research yielded 33 previously
      published checklists, from which we extracted a list of 75 potential items. At
      the consensus meeting, participants shortened the list to a 25 item checklist, by
      using evidence, whenever available. A prototype of a flow diagram provides
      information about the method of patient recruitment, the order of test execution,
      and the numbers of patients undergoing the test under evaluation and the
      reference standard, or both. CONCLUSIONS: Evaluation of research depends on
      complete and accurate reporting. If medical journals adopt the STARD checklist
      and flow diagram, the quality of reporting of studies of diagnostic accuracy
      should improve to the advantage of clinicians, researchers, reviewers, journals,
      and the public.

PMID- 12511464
TI  - The making of a disease: female sexual dysfunction.

PMID- 12511465
TI  - Trainees' attitudes to shift work depend on grade and specialty.

PMID- 12511466
TI  - Delayed discharge and hospital congestion. One nettle to be grasped is
      discharging patients against their or their families' wishes . . .

PMID- 12511467
TI  - Emergency pyramid is inverting already.

PMID- 12511468
TI  - Managing acute appendicitis. Technology at expense of clinical evaluation will
      diminish quality of care.

PMID- 12511469
TI  - Preventing and treating eclamptic seizures. Will magnesium sulphate for pre
      eclampsia really help?

PMID- 12511470
TI  - Alcohol handrubs v soap. Finnish experience shows that alcohol rubs are good for
      hands.

PMID- 12511471
TI  - Sustaining medical education is difficult in poor countries.

PMID- 12511472
TI  - Outdated drugs may be useful.

PMID- 12511473
TI  - Alosetron for irritable bowel syndrome. Senior vice president of GlaxoSmithKline
      responds.

PMID- 12511474
TI  - Preventing stroke with ramipril--authors' reply.

PMID- 12511475
TI  - More travel advice and fewer vaccinations are needed.

PMID- 12511476
TI  - Screening populations at low risk carries high risks.

PMID- 12511477
TI  - Embryo selection for complex traits is impracticable.

PMID- 12511478
TI  - Surgical training in the developing world.

PMID- 12511479
TI  - Practising medicine in a multicultural society.

PMID- 12511480
TI  - Just who are tomorrow's doctors?

PMID- 12511481
TI  - Running an induction course.

PMID- 12511482
TI  - Just toothpicks and logic: how some labs succeed at solving complex problems.

PMID- 12511483
TI  - CelI, a noncellulosomal family 9 enzyme from Clostridium thermocellum, is a
      processive endoglucanase that degrades crystalline cellulose.
AB  - The family 9 cellulase gene celI of Clostridium thermocellum, was previously
      cloned, expressed, and characterized (G. P. Hazlewood, K. Davidson, J. I. Laurie,
      N. S. Huskisson, and H. J. Gilbert, J. Gen. Microbiol. 139:307-316, 1993). We
      have recloned and sequenced the entire celI gene and found that the published
      sequence contained a 53-bp deletion that generated a frameshift mutation,
      resulting in a truncated and modified C-terminal segment of the protein. The
      enzymatic properties of the wild-type protein were characterized and found to
      conform to those of other family 9 glycoside hydrolases with a so-called theme B
      architecture, where the catalytic module is fused to a family 3c carbohydrate
      binding module (CBM3c); CelI also contains a C-terminal CBM3b. The intact
      recombinant CelI exhibited high levels of activity on all cellulosic substrates
      tested, with pH and temperature optima of 5.5 and 70 degrees C, respectively,
      using carboxymethylcellulose as a substrate. Native CelI was capable of
      solubilizing filter paper, and the distribution of reducing sugar between the
      soluble and insoluble fractions suggests that the enzyme acts as a processive
      cellulase. A truncated form of the enzyme, lacking the C terminal CBM3b, failed
      to bind to crystalline cellulose and displayed reduced activity toward insoluble
      substrates. A truncated form of the enzyme, in which both the cellulose-binding
      CBM3b and the fused CBM3c were removed, failed to exhibit significant levels of
      activity on any of the substrates examined. This study underscores the general
      nature of this type of enzymatic theme, whereby the fused CBM3c plays a critical
      accessory role for the family 9 catalytic domain and changes its character to
      facilitate processive cleavage of recalcitrant cellulose substrates.

PMID- 12511484
TI  - Characterization of benzoyl coenzyme A biosynthesis genes in the enterocin
      producing bacterium "Streptomyces maritimus".
AB  - The novel benzoyl coenzyme A (benzoyl-CoA) biosynthesis pathway in "Streptomyces
      maritimus" was investigated through a series of target-directed mutations. Genes
      involved in benzoyl-CoA formation were disrupted through single-crossover
      homologous recombination, and the resulting mutants were analyzed for their
      ability to biosynthesize the benzoyl-CoA-primed polyketide antibiotic enterocin.
      Inactivation of the unique phenylalanine ammonia-lyase-encoding gene encP was
      previously shown to be absolutely required for benzoyl-CoA formation in "S.
      maritimus". The fatty acid beta-oxidation-related genes encH, -I, and -J, on the
      other hand, are necessary but not required. In each case, the yield of benzoyl
      CoA-primed enterocin dropped below wild-type levels. We attribute the reduced
      benzoyl-CoA formation in these specific mutants to functional substitution and
      cross-talk between the products of genes encH, -I, and -J and the enzyme
      homologues of primary metabolism. Disruption of the benzoate-CoA ligase encN gene
      did not perturb enterocin production, however, demonstrating that encN is
      extraneous and that benzoic acid is not a pathway intermediate. EncN rather
      serves as a substitute pathway for utilizing exogenous benzoic acid. These
      experiments provide further support that benzoyl-CoA is formed in a novel
      bacterial pathway that resembles the eukaryotic assembly of benzoyl-CoA from
      phenylalanine via a beta-oxidative path.

PMID- 12511485
TI  - Biochemical characterization of a mutationally altered protein translocase:
      proton motive force stimulation of the initiation phase of translocation.
AB  - Protein translocation across the Escherichia coli plasma membrane is facilitated
      by concerted actions of the SecYEG integral membrane complex and the SecA ATPase.
      A secY mutation (secY39) affects Arg357, an evolutionarily conserved and
      functionally important residue, and impairs the translocation function in vivo
      and in vitro. In this study, we used the "superactive" mutant forms of SecA,
      which suppress the SecY39 deficiency, to characterize the mutationally altered
      SecY39EG translocase. It was found that SecY39-mediated preprotein translocation
      exhibited absolute dependence on the proton motive force. The proton motive force
      dependent step proved to lie before signal peptide cleavage. We suggest that the
      proton motive force assists in the initiation phase of protein translocation.

PMID- 12511486
TI  - Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity
      islet by RlrA.
AB  - The proper temporal expression of virulence genes during infection is crucial to
      the infectious life cycle of microbial pathogens, particularly in pathogens that
      encounter a multitude of environments in eukaryotic hosts. Streptococcus
      pneumoniae normally colonizes the nasopharynges of healthy adults but can cause a
      range of diseases at a variety of host sites. Transcriptional regulators that are
      essential for full virulence of S. pneumoniae in different animal models have
      been identified. One such regulator, rlrA, is required for colonization of the
      nasopharynx and lung infection but is dispensable for systemic infection.
      Previous work has shown that rlrA lies in a 12-kb pathogenicity islet,
      divergently opposed to three putative sortase-anchored surface proteins and three
      sortase enzymes. In addition to rlrA, one of the putative surface proteins and
      one of the sortases have also been shown to be essential for lung infection. In
      this work, we demonstrate that RlrA is a positive regulator of all seven genes in
      the rlrA pathogenicity islet, with transcriptional activation occurring at four
      different promoters in the islet with AT-rich sequences. These promoters direct
      the expression of rlrA itself, the three sortases, rrgA, and rrgBC. These data
      are consistent with the model whereby the rlrA pathogenicity islet acts in an
      autonomous manner to alter the bacterial surface components that interact with
      the pulmonary and nasopharyngeal environments.

PMID- 12511487
TI  - Features of Rhodobacter sphaeroides CcmFH.
AB  - In this study, the in vivo function and properties of two cytochrome c maturation
      proteins, CcmF and CcmH from Rhodobacter sphaeroides, were analyzed. Strains
      lacking CcmH or both CcmF and CcmH are unable to grow under anaerobic conditions
      where c-type cytochromes are required, demonstrating their critical role in the
      assembly of these electron carriers. Consistent with this observation, strains
      lacking both CcmF and CcmH are deficient in c-type cytochromes when assayed under
      permissive growth conditions. In contrast, under permissive growth conditions,
      strains lacking only CcmH contain several soluble and membrane-bound c-type
      cytochromes, albeit at reduced levels, suggesting that this bacterium has a CcmH
      independent route for their maturation. In addition, the function of CcmH that is
      needed to support anaerobic growth can be replaced by adding cysteine or cystine
      to growth media. The ability of exogenous thiol compounds to replace CcmH
      provides the first physiological evidence for a role of this protein in thiol
      chemistry during c-type cytochrome maturation. The properties of R. sphaeroides
      cells containing translational fusions between CcmF and CcmH and either
      Escherichia coli alkaline phosphatase or beta-galactosidase suggest that they are
      each integral cytoplasmic membrane proteins with their presumed catalytic domains
      facing the periplasm. Analysis of CcmH shows that it is synthesized as a higher
      molecular-weight precursor protein with an N-terminal signal sequence.

PMID- 12511488
TI  - Salmonella enterica serovar typhimurium rdoA is growth phase regulated and
      involved in relaying Cpx-induced signals.
AB  - The disulfide oxidoreductase, DsbA, mediates disulfide bond formation in proteins
      as they enter or pass through the periplasm of gram-negative bacteria. Although
      DsbA function has been well characterized, less is known about the factors that
      control its expression. Previous studies with Escherichia coli demonstrated that
      dsbA is part of a two-gene operon that includes an uncharacterized, upstream
      gene, yihE, that is positively regulated via the Cpx stress response pathway. To
      clarify the role of the yihE homologue on dsbA expression in Salmonella enterica
      serovar Typhimurium, the effect of this gene (termed rdoA) on the regulation of
      dsbA expression was investigated. Transcriptional assays assessing rdoA promoter
      activity showed growth phase-dependent expression with maximal activity in
      stationary phase. Significant quantities of rdoA and dsbA transcripts exist in
      serovar Typhimurium, but only extremely low levels of rdoA-dsbA cotranscript were
      detected. Activation of the Cpx system in serovar Typhimurium increased synthesis
      of both rdoA- and dsbA-specific transcripts but did not significantly alter the
      levels of detectable cotranscript. These results indicate that Cpx-mediated
      induction of dsbA transcription in serovar Typhimurium does not occur through an
      rdoA-dsbA cotranscript. A deletion of the rdoA coding region was constructed to
      definitively test the relevance of the rdoA-dsbA cotranscript to dsbA expression.
      The absence of RdoA affects DsbA expression levels when the Cpx system is
      activated, and providing rdoA in trans complements this phenotype, supporting the
      hypothesis that a bicistronic mechanism is not involved in serovar Typhimurium
      dsbA regulation. The rdoA null strain was also shown to be altered in flagellar
      phase variation. First it was found that induction of the Cpx stress response
      pathway switched flagellar synthesis to primarily phase 2 flagellin, and this
      effect was then found to be abrogated in the rdoA null strain, suggesting the
      involvement of RdoA in mediating Cpx-related signaling.

PMID- 12511489
TI  - Expression of spoT in Borrelia burgdorferi during serum starvation.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted by the
      tick Ixodes scapularis. A 2.9-kb fragment containing a putative spoT gene was
      isolated from B. burgdorferi genomic DNA by PCR amplification and cloned into a
      pBAD24 vector. The cloned gene complemented Escherichia coli mutant strain
      CF1693, which contains deletions of both the relA and spoT genes. The spoT gene
      in E. coli encodes a bifunctional enzyme capable of synthesizing and degrading
      (p)ppGpp, which mediates the stringent response during carbon source starvation.
      B. burgdorferi has been reported to have a stress response to serum starvation.
      Thin-layer chromatography was used to detect (p)ppGpp extracted from
      H(3)(32)PO(4)-labeled B. burgdorferi cells starved for serum in RPMI. B.
      burgdorferi spoT gene expression was characterized during fatty acid starvation.
      Northern analysis of spoT revealed detectable message at 2.5 min of starvation in
      RPMI. Expression of spoT during serum starvation increased approximately 6-fold
      during the 30 min that starvation conditions were maintained. Further, expression
      of spoT decreased when serum was added to serum-starved cells. Reverse
      transcriptase PCR (RT-PCR) was used to detect spoT mRNA from approximately 10(6)
      cells starved for serum in RPMI for 2.5 to 30 min or incubated in tick saliva for
      15 min. Northern blot analysis suggests that spoT transcript was approximately
      900 nucleotides in length. RT-PCR amplification of the transcript using several
      sets of primers confirmed this finding. Additionally, a truncated clone
      containing only the first 950 bp of the 2,001-bp spoT open reading frame was able
      to complement E. coli CF1693. The data suggest that B. burgdorferi exhibits a
      stringent response to serum starvation and during incubation in tick saliva.

PMID- 12511490
TI  - Genetic analysis of the AdnA regulon in Pseudomonas fluorescens: nonessential
      role of flagella in adhesion to sand and biofilm formation.
AB  - AdnA is a transcription factor in Pseudomonas fluorescens that affects flagellar
      synthesis, biofilm formation, and sand adhesion. To identify the AdnA regulon, we
      used a promoterless Tn5-lacZ element to study the phenotypes of insertion mutants
      in the presence and absence of AdnA. Of 12,000 insertions, we identified seven
      different putative open reading frames (ORFs) activated by AdnA (named aba for
      activated by AdnA). aba120 and aba177 showed homology to flgC and flgI,
      components of the basal body of the flagella in Pseudomonas aeruginosa. Two other
      insertions, aba18 and aba51, disrupted genes affecting chemotaxis. The mutant
      loci aba160 (possibly affecting lipopolysaccharide synthesis) and aba175 (unknown
      function) led to loss of flagella. The mutant bearing aba203 became motile when
      complemented with adnA, but the mutated gene showed no similarity to known genes.
      Curiously, aba18, aba51, aba160, and aba203 mutants formed biofilms even in the
      absence of AdnA, suppressing the phenotype of the adnA deletion mutant. The
      combined findings suggest that flagella are nonessential for sand attachment or
      biofilm formation. Sequence and promoter analyses indicate that AdnA affects at
      least 23 ORFs either directly or by polar effects. These results support the
      concept that AdnA regulates cell processes other than those directly related to
      flagellar synthesis and define a broader cadre of genes in P. fluorescens than
      that described so far for its homolog, FleQ, in P. aeruginosa.

PMID- 12511491
TI  - Bioenergetic properties of the thermoalkaliphilic Bacillus sp. strain TA2.A1.
AB  - The thermoalkaliphilic Bacillus sp. strain TA2.A1 was able to grow in pH
      controlled batch culture containing a nonfermentable growth substrate from pH 7.5
      to 10.0 with no significant change in its specific growth rate, demonstrating
      that this bacterium is a facultative alkaliphile. Growth at pH 10.0 was sensitive
      to the protonophore carbonyl cyanide m-chlorophenylhydrazone, suggesting that a
      proton motive force (Deltap) generated via aerobic respiration was an obligate
      requirement for growth of strain TA2.A1. Strain TA2.A1 exhibited intracellular pH
      homeostasis as the external pH increased from 7.5 to 10.0; however, the maximum
      DeltapH generated over this pH range was only 1.1 units at an external pH of 9.5.
      The membrane potential (Deltapsi) was maintained between -114 mV and -150 mV, and
      little significant change was observed over the pH range for growth. In contrast,
      the Deltap declined from -164 mV at pH 7.5 to approximately -78 mV at pH 10.0. An
      inwardly directed sodium motive force (DeltapNa(+)) of -100 mV at pH 10.0
      indicated that cellular processes (i.e., solute transport) dependent on a sodium
      gradient would not be affected by the adverse Deltap. The phosphorylation
      potential of strain TA2.A1 was maintained between -300 mV and -418 mV, and the
      calculated H(+)/ATP stoichiometry of the ATP synthase increased from 2.0 at pH
      7.5 to 5.7 at pH 10.0. Based on these data, vigorous growth of strain TA2.A1
      correlated well with the DeltapNa(+), phosphorylation potential, and the ATP/ADP
      ratio, but not with Deltap. This communication represents the first report on the
      bioenergetics of an extremely thermoalkaliphilic aerobic bacterium.

PMID- 12511492
TI  - Regulation of the Bacillus subtilis heat shock gene htpG is under positive
      control.
AB  - The heat shock genes of Bacillus subtilis are assigned to four classes on the
      basis of their regulation mechanisms. While classes I and III are negatively
      controlled by two different transcriptional repressors, class II is regulated by
      the alternative sigma factor sigma(B). All heat shock genes with unidentified
      regulatory mechanisms, among them htpG, constitute class IV. Here, we show that
      expression of htpG is under positive control. We identified a DNA sequence
      (GAAAAGG) located downstream of the sigma(A)-dependent promoter of htpG. The heat
      inducibility of the promoter could be destroyed by inversion, nucleotide
      replacements, or removal of this DNA sequence. Fusion of this sequence to the
      vegetative lepA promoter conferred heat inducibility. Furthermore, we were able
      to show that the heat induction factor is dependent on the absolute temperature
      rather than the temperature increment and that nonnative proteins within the
      cytoplasm fail to induce htpG.

PMID- 12511493
TI  - Combinatorial redesign of the DNA binding specificity of a prokaryotic helix-turn
      helix repressor.
AB  - Redesign of the bacteriophage 434 Cro repressor was accomplished by using an in
      vivo genetic screening system to identify new variants that specifically bound
      previously unrecognized DNA sequences. Site-directed, combinatorial mutagenesis
      of the 434 Cro helix-turn-helix (HTH) motif generated libraries of new variants
      which were screened for binding to new target sequences. Multiple mutations of
      434 Cro that functionally converted wild-type (wt) 434 Cro DNA binding-sequence
      specificity to that of a lambda bacteriophage-specific repressor were identified.
      The libraries contained variations within the HTH sequence at only three
      positions. In vivo and in vitro analysis of several of the identified 434 Cro
      variants showed that the relatively few changes in the recognition helix of the
      HTH motif of 434 Cro resulted in specific and tight binding of the target DNA
      sequences. For the best 434 Cro variant identified, an apparent K(d) for lambda
      O(R)3 of 1 nM was observed. In competition experiments, this Cro variant was
      observed to be highly selective. We conclude that functional 434 Cro repressor
      variants with new DNA binding specificities can be generated from wt 434 Cro by
      mutating just the recognition helix. Important characteristics of the screening
      system responsible for the successful identifications are discussed. Application
      of the techniques presented here may allow the identification of DNA binding
      protein variants that functionally affect DNA regulatory sequences important in
      disease and industrial and biotechnological processes.

PMID- 12511494
TI  - Targeted disruption of the alpha-amylase gene in the hyperthermophilic archaeon
      Sulfolobus solfataricus.
AB  - Sulfolobus solfataricus secretes an acid-resistant alpha-amylase (amyA) during
      growth on starch as the sole carbon and energy source. Synthesis of this activity
      is subject to catabolite repression. To better understand alpha-amylase function
      and regulation, the structural gene was identified and disrupted and the
      resulting mutant was characterized. Internal alpha-amylase peptide sequences
      obtained by tandem mass spectroscopy were used to identify the amyA coding
      sequence. Anti-alpha-amylase antibodies raised against the purified protein
      immunoprecipitated secreted alpha-amylase activity and verified the enzymatic
      identity of the sequenced protein. A new gene replacement method was used to
      disrupt the amyA coding sequence by insertion of a modified allele of the S.
      solfataricus lacS gene. PCR and DNA sequence analysis were used to characterize
      the altered amyA locus in the recombinant strain. The amyA::lacS mutant lost the
      ability to grow on starch, glycogen, or pullulan as sole carbon and energy
      sources. During growth on a non-catabolite-repressing carbon source with added
      starch, the mutant produced no detectable secreted amylase activity as determined
      by enzyme assay, plate assay, or Western blot analysis. These results clarify the
      biological role of the alpha-amylase and provide additional methods for the
      directed genetic manipulation of the S. solfataricus genome.

PMID- 12511495
TI  - Identification of secretion determinants of the Bordetella pertussis BrkA
      autotransporter.
AB  - The autotransporters comprise a functionally diverse family of gram-negative
      proteins that mediate their own export across the bacterial outer membrane. They
      consist of an amino-terminal passenger region called the "alpha-domain" and the
      structural hallmark of the autotransporter family, a carboxy-terminal transporter
      region usually referred to as the "beta-domain." The passenger region can be
      quite diverse and constitutes the effector functions of these proteins, whereas
      the C-terminal region is conserved and is responsible for translocating the
      passenger moiety across the outer membrane. BrkA is the 103-kDa autotransporter
      protein in Bordetella pertussis that is cleaved to yield a 73-kDa N-terminal
      alpha-domain and a 30-kDa C-terminal beta-domain. We have previously shown that a
      recombinant form of the beta-domain of BrkA is capable of forming channels in
      artificial membranes. Here, we define two additional secretion determinants of
      BrkA. N-terminal sequencing of the 73-kDa BrkA passenger from B. pertussis and
      Escherichia coli revealed that BrkA has a 42-amino-acid signal peptide. In
      addition, deletion analysis of BrkA identified a 31- to 39-amino-acid region
      found immediately upstream of the beta-domain that was essential for surface
      expression. This 31- to 39-amino-acid linker region, together with the beta
      domain, defines the minimal BrkA translocation unit. The linker region may also
      serve to anchor the BrkA passenger to the bacterial surface.

PMID- 12511496
TI  - Characterization of a novel intracellular endopeptidase of the alpha/beta
      hydrolase family from Streptomyces coelicolor A3(2).
AB  - In a proteasome-lacking mutant of Streptomyces coelicolor A3(2), an intracellular
      enzyme with chymotrypsin-like activity, absent from the wild type, was detected.
      Complementation that restored proteasome function did not suppress expression of
      the endopeptidase. Since the enzyme was not found in two other S. coelicolor
      proteasome mutants, its expression probably resulted from a secondary mutation
      arisen in the proteasome mutant. Purification of the endopeptidase revealed its
      identity to SCO7095, a putative hydrolase encoded by the S. coelicolor A3(2)
      genome with no known homologue. Based on the prediction of a Ser-Asp-His
      catalytic triad and an alpha/beta hydrolase fold, SCO7095 was assigned to
      peptidase clan SC. N-terminally His-tagged SCO7095 was efficiently expressed in
      Escherichia coli cells and purified for further characterization. Although
      SCO7095 is distantly related to several proline iminopeptidases, including
      Thermoplasma acidophilum tricorn-interacting F1, no aminopeptidase activity was
      detected. On synthetic substrates, the monomeric enzyme exhibited not only
      chymotrypsin-like activity but also thrombin-like activity.

PMID- 12511497
TI  - Characterization of a cellulase containing a family 30 carbohydrate-binding
      module (CBM) derived from Clostridium thermocellum CelJ: importance of the CBM to
      cellulose hydrolysis.
AB  - Clostridium thermocellum CelJ is a modular enzyme containing a family 30
      carbohydrate-binding module (CBM) and a family 9 catalytic module at its N
      terminal moiety. To investigate the functions of the CBM and the catalytic
      module, truncated derivatives of CelJ were constructed and characterized.
      Isothermal titration calorimetric studies showed that the association constants
      (K(a)) of the CBM polypeptide (CBM30) for the binding of cellopentaose and
      cellohexaose were 1.2 x 10(4) and 6.4 x 10(4) M(-1), respectively, and that the
      binding of CBM30 to these ligands is enthalpically driven. Qualitative analyses
      showed that CBM30 had strong affinity for cellulose and beta-1,3-1,4-mixed glucan
      such as barley beta-glucan and lichenan. Analyses of the hydrolytic action of the
      enzyme comprising the CBM and the catalytic module showed that the enzyme is a
      processive endoglucanse with strong activity towards carboxymethylcellulose,
      barley beta-glucan and lichenan. By contrast, the catalytic module polypeptide
      devoid of the CBM showed negligible activity toward these substrates. These
      observations suggest that the CBM is extremely important not only because it
      mediates the binding of the enzyme to the substrates but also because it
      participates in the catalytic function of the enzyme or contributes to
      maintaining the correct tertiary structure of the family 9 catalytic module for
      expressing enzyme activity.

PMID- 12511498
TI  - Convergent evolution of Amadori opine catabolic systems in plasmids of
      Agrobacterium tumefaciens.
AB  - Deoxyfructosyl glutamine (DFG, referred to elsewhere as dfg) is a naturally
      occurring Amadori compound found in rotting fruits and vegetables. DFG also is an
      opine and is found in tumors induced by chrysopine-type strains of Agrobacterium
      tumefaciens. Such strains catabolize this opine via a pathway coded for by their
      plasmids. NT1, a derivative of the nopaline-type A. tumefaciens strain C58
      lacking pTiC58, can utilize DFG as the sole carbon source. Genes for utilization
      of DFG were mapped to the 543-kb accessory plasmid pAtC58. Two cosmid clones of
      pAtC58 allowed UIA5, a plasmid-free derivative of C58, harboring pSa-C that
      expresses MocC (mannopine [MOP] oxidoreductase that oxidizes MOP to DFG), to grow
      by using MOP as the sole carbon source. Genetic analysis of subclones indicated
      that the genes for utilization of DFG are located in a 6.2-kb BglII (Bg2) region
      adjacent to repABC-type genes probably responsible for the replication of pAtC58.
      This region contains five open reading frames organized into at least two
      transcriptional soc (santhopine catabolism) groups: socR and socABCD. Nucleotide
      sequence analysis and analyses of transposon-insertion mutations in the region
      showed that SocR negatively regulates the expression of socR itself and socABCD.
      SocA and SocB are responsible for transport of DFG and MOP. SocA is a homolog of
      known periplasmic amino acid binding proteins. The N-terminal half of SocB is a
      homolog of the transmembrane transporter proteins for several amino acids, and
      the C-terminal half is a homolog of the transporter-associated ATP-binding
      proteins. SocC and SocD could be responsible for the enzymatic degradation of
      DFG, being homologs of sugar oxidoreductases and an amadoriase from
      Corynebacterium sp., respectively. The protein products of socABCD are not
      related at the amino acid sequence level to those of the moc and mot genes of Ti
      plasmids responsible for utilization of DFG and MOP, indicating that these two
      sets of genes and their catabolic pathways have evolved convergently from
      independent origins.

PMID- 12511499
TI  - Transcription of the Salmonella invasion gene activator, hilA, requires HilD
      activation in the absence of negative regulators.
AB  - Salmonella enterica serovar Typhimurium causes human gastroenteritis and a
      systemic typhoid-like infection in mice. Infection is initiated by entry of the
      bacteria into intestinal epithelial cells and is mediated by a type III secretion
      system that is encoded by genes in Salmonella pathogenicity island 1. The
      expression of invasion genes is tightly regulated by environmental conditions
      such as oxygen and osmolarity, as well as by many bacterial factors. The hilA
      gene encodes an OmpR/ToxR family transcriptional regulator that activates the
      expression of invasion genes in response to both environmental and genetic
      regulatory factors. HilD is an AraC/XylS regulator that has been postulated to
      act as a derepressor of hilA expression that promotes transcription by
      interfering with repressor binding at the hilA promoter. Our research group has
      identified four genes (hilE, hha, pag, and ams) that negatively affect hilA
      transcription. Since the postulated function of HilD at the hilA promoter is to
      counteract the effects of repressors, we examined this model by measuring
      hilA::Tn5lacZY expression in strains containing negative regulator mutations in
      the presence or absence of functional HilD. Single negative regulator mutations
      caused significant derepression of hilA expression, and two or more negative
      regulator mutations led to very high level expression of hilA. However, in all
      strains tested, the absence of hilD resulted in low-level expression of hilA,
      suggesting that HilD is required for activation of hilA expression, whether or
      not negative regulators are present. We also observed that deletion of the HilD
      binding sites in the chromosomal hilA promoter severely decreased hilA
      expression. In addition, we found that a single point mutation at leucine 289 in
      the C-terminal domain of the alpha subunit of RNA polymerase leads to very low
      levels of hilA::Tn5lacZY expression, suggesting that HilD activates transcription
      of hilA by contacting and recruiting RNA polymerase to the hilA promoter.

PMID- 12511500
TI  - FlhD/FlhC is a regulator of anaerobic respiration and the Entner-Doudoroff
      pathway through induction of the methyl-accepting chemotaxis protein Aer.
AB  - The regulation by two transcriptional activators of flagellar expression (FlhD
      and FlhC) and the chemotaxis methyl-accepting protein Aer was studied with glass
      slide DNA microarrays. An flhD::Kan insertion and an aer deletion were
      independently introduced into two Escherichia coli K-12 strains, and the effects
      upon gene regulation were investigated. Altogether, the flhD::Kan insertion
      altered the expression of 29 operons of known function. Among them was Aer, which
      in turn regulated a subset of these operons, namely, the ones involved in
      anaerobic respiration and the Entner-Doudoroff pathway. In addition, FlhD/FlhC
      repressed enzymes involved in aerobic respiration and regulated many other
      metabolic enzymes and transporters in an Aer-independent manner. Expression of 12
      genes of uncharacterized function was also affected. FlhD increased gltBD,
      gcvTHP, and ompT expression. The regulation of half of these genes was
      subsequently confirmed with reporter gene fusions, enzyme assays, and real-time
      PCR. Growth phenotypes of flhD and flhC mutants were determined with Phenotype
      MicroArrays and correlated with gene expression.

PMID- 12511501
TI  - Different evolutionary constraints on chemotaxis proteins CheW and CheY revealed
      by heterologous expression studies and protein sequence analysis.
AB  - CheW and CheY are single-domain proteins from a signal transduction pathway that
      transmits information from transmembrane receptors to flagellar motors in
      bacterial chemotaxis. In various bacterial and archaeal species, the cheW and
      cheY genes are usually encoded within homologous chemotaxis operons. We examined
      evolutionary changes in these two proteins from distantly related proteobacterial
      species, Escherichia coli and Azospirillum brasilense. We analyzed the functions
      of divergent CheW and CheY proteins from A. brasilense by heterologous expression
      in E. coli wild-type and mutant strains. Both proteins were able to specifically
      inhibit chemotaxis of a wild-type E. coli strain; however, only CheW from A.
      brasilense was able to restore signal transduction in a corresponding mutant of
      E. coli. Detailed protein sequence analysis of CheW and CheY homologs from the
      two species revealed substantial differences in the types of amino acid
      substitutions in the two proteins. Multiple, but conservative, substitutions were
      found in CheW homologs. No severe mismatches were found between the CheW homologs
      in positions that are known to be structurally or functionally important.
      Substitutions in CheY homologs were found to be less conservative and occurred in
      positions that are critical for interactions with other components of the signal
      transduction pathway. Our findings suggest that proteins from the same cellular
      pathway encoded by genes from the same operon have different evolutionary
      constraints on their structures that reflect differences in their functions.

PMID- 12511502
TI  - Genomic comparison of Salmonella enterica serovars and Salmonella bongori by use
      of an S. enterica serovar typhimurium DNA microarray.
AB  - The genus Salmonella consists of over 2,200 serovars that differ in their host
      range and ability to cause disease despite their close genetic relatedness. The
      genetic factors that influence each serovar's level of host adaptation, how they
      evolved or were acquired, their influence on the evolution of each serovar, and
      the phylogenic relationships between the serovars are of great interest as they
      provide insight into the mechanisms behind these differences in host range and
      disease progression. We have used an Salmonella enterica serovar Typhimurium
      spotted DNA microarray to perform genomic hybridizations of various serovars and
      strains of both S. enterica (subspecies I and IIIa) and Salmonella bongori to
      gain insight into the genetic organization of the serovars. Our results are
      generally consistent with previously published DNA association and multilocus
      enzyme electrophoresis data. Our findings also reveal novel information. We
      observe a more distant relationship of serovar Arizona (subspecies IIIa) from the
      subspecies I serovars than previously measured. We also observe variability in
      the Arizona SPI-2 pathogenicity island, indicating that it has evolved in a
      manner distinct from the other serovars. In addition, we identify shared genetic
      features of S. enterica serovars Typhi, Paratyphi A, and Sendai that parallel
      their unique ability to cause enteric fever in humans. Therefore, whereas the
      taxonomic organization of Salmonella into serogroups provides a good first
      approximation of genetic relatedness, we show that it does not account for
      genomic changes that contribute to a serovar's degree of host adaptation.

PMID- 12511503
TI  - Microcystin biosynthesis in planktothrix: genes, evolution, and manipulation.
AB  - Microcystins represent an extraordinarily large family of cyclic heptapeptide
      toxins that are nonribosomally synthesized by various cyanobacteria. Microcystins
      specifically inhibit the eukaryotic protein phosphatases 1 and 2A. Their
      outstanding variability makes them particularly useful for studies on the
      evolution of structure-function relationships in peptide synthetases and their
      genes. Analyses of microcystin synthetase genes provide valuable clues for the
      potential and limits of combinatorial biosynthesis. We have sequenced and
      analyzed 55.6 kb of the potential microcystin synthetase gene (mcy) cluster from
      the filamentous cyanobacterium Planktothrix agardhii CYA 126. The cluster
      contains genes for peptide synthetases (mcyABC), polyketide synthases (PKSs;
      mcyD), chimeric enzymes composed of peptide synthetase and PKS modules (mcyEG), a
      putative thioesterase (mcyT), a putative ABC transporter (mcyH), and a putative
      peptide-modifying enzyme (mcyJ). The gene content and arrangement and the
      sequence of specific domains in the gene products differ from those of the mcy
      cluster in Microcystis, a unicellular cyanobacterium. The data suggest an
      evolution of mcy clusters from, rather than to, genes for nodularin (a related
      pentapeptide) biosynthesis. Our data do not support the idea of horizontal gene
      transfer of complete mcy gene clusters between the genera. We have established a
      protocol for stable genetic transformation of Planktothrix, a genus that is
      characterized by multicellular filaments exhibiting continuous motility. Targeted
      mutation of mcyJ revealed its function as a gene coding for a O
      methyltransferase. The mutant cells produce a novel microcystin variant
      exhibiting reduced inhibitory activity toward protein phosphatases.

PMID- 12511504
TI  - TmRNA is required for correct timing of DNA replication in Caulobacter
      crescentus.
AB  - SsrA, or tmRNA, is a small RNA that interacts with selected translating ribosomes
      to target the nascent polypeptides for degradation. Here we report that SsrA
      activity is required for normal timing of the G(1)-to-S transition in Caulobacter
      crescentus. A deletion of the ssrA gene, or of the gene encoding SmpB, a protein
      required for SsrA activity, results in a specific delay in the cell cycle during
      the G(1)-to-S transition. The ssrA deletion phenotype is not due to accumulation
      of stalled ribosomes, because the deletion is not complemented by a mutated
      version of SsrA that releases ribosomes but does not target proteins for
      degradation. Degradation of the CtrA response regulator normally coincides with
      initiation of DNA replication, but in strains lacking SsrA activity there is a 40
      min delay between the degradation of CtrA and replication initiation. This
      uncoupling of initiation of replication from CtrA degradation indicates that
      there is an SsrA-dependent pathway required for correct timing of DNA
      replication.

PMID- 12511505
TI  - Functional and mutational analysis of conjugative transfer region 2 (Tra2) from
      the IncHI1 plasmid R27.
AB  - The transfer 2 region (Tra2) of the conjugative plasmid drR27 (derepressed R27)
      was analyzed by PSI-BLAST, insertional mutagenesis, genetic complementation, and
      an H-pilus assay. Tra2 contains 11 mating-pair formation (Mpf) genes that are
      essential for conjugative transfer, 9 of which are essential for H-pilus
      production (trhA, -L, -E, -K, -B, -V, -C, -P, and -W). TrhK has similarity to
      secretin proteins, suggesting a mechanism by which DNA could traverse the outer
      membrane of donors. The remaining two Mpf genes, trhU and trhN, play an auxiliary
      role in H-pilus synthesis and are proposed to be involved in DNA transfer and
      mating-pair stabilization, respectively. Conjugative transfer abilities were
      restored for each mutant when complemented with the corresponding transfer gene.
      In addition to the essential Mpf genes, three genes, trhO, trhZ, and htdA,
      modulate R27 transfer frequency. Disruption of trhO and trhZ severely reduced the
      transfer frequencies of drR27, whereas disruption of htdA greatly increased the
      transfer frequency of wild-type R27 to drR27 levels. A comparison of the
      essential transfer genes encoded by the Tra2 and Tra1 (T. D. Lawley, M. W.
      Gilmour, J. E. Gunton, L. J. Standeven, and D. E. Taylor, J. Bacteriol. 184:2173
      2183, 2002) of R27 to other transfer systems illustrates that the R27 conjugative
      transfer system is a chimera composed of IncF-like and IncP-like transfer
      systems. Furthermore, the Mpf/type IV secretion systems encoded by IncH and IncF
      transfer systems are distinct from that of the IncP transfer system. The
      phenotypic and ecological significance of these observations is discussed.

PMID- 12511506
TI  - Accumulation of S-adenosyl-L-methionine enhances production of actinorhodin but
      inhibits sporulation in Streptomyces lividans TK23.
AB  - S-Adenosyl-L-methionine synthetase (SAM-s) catalyzes the biosynthesis of SAM from
      ATP and L-methionine. Despite extensive research with many organisms, its role in
      Streptomyces sp. remains unclear. In the present study, the putative SAM-s gene
      was isolated from a spectinomycin producer, Streptomyces spectabilis. The
      purified protein from the transformed Escherichia coli with the isolated gene
      synthesized SAM from L-methionine and ATP in vitro, strongly indicating that the
      isolated gene indeed encoded the SAM-s protein. The overexpression of the SAM-s
      gene in Streptomyces lividans TK23 inhibited sporulation and aerial mycelium
      formation but enhanced the production of actinorhodin in both agar plates and
      liquid media. Surprisingly, the overexpressed SAM was proven by Northern analysis
      to increase the production of actinorhodin through the induction of actII-ORF4, a
      transcription activator of actinorhodin biosynthetic gene clusters. In addition,
      we found that a certain level of intracellular SAM is critical for the induction
      of antibiotic biosynthetic genes, since the control strain harboring only the
      plasmid DNA did not show any induction of actII-ORF4 until it reached a certain
      level of SAM in the cell. From these results, we concluded that the SAM plays
      important roles as an intracellular factor in both cellular differentiation and
      antibiotic production in Streptomyces sp.

PMID- 12511507
TI  - Enhanced expression of S-adenosylmethionine synthetase causes overproduction of
      actinorhodin in Streptomyces coelicolor A3(2).
AB  - We found that a 46-kDa protein is highly expressed in an actinorhodin
      overproducing Streptomyces coelicolor A3(2) mutant (KO-179), which exhibited a
      low-level resistance to streptomycin. The protein was identified as S
      adenosylmethionine (SAM) synthetase, which is a product of the metK gene. Enzyme
      assay revealed that SAM synthetase activity in strain KO-179 was 5- to 10-fold
      higher than in wild-type cells. The elevation of SAM synthetase activity was
      found to be associated with an increase in the level of intracellular SAM. RNase
      protection assay revealed that the metK gene was transcribed from two distinct
      promoters (p1 and p2) and that enhanced expression of the MetK protein in the
      mutant strain KO-179 was attributed to elevated transcription from metKp2.
      Strikingly, the introduction of a high-copy-number plasmid containing the metK
      gene into wild-type cells resulted in a precocious hyperproduction of
      actinorhodin. Furthermore, the addition of SAM to the culture medium induced Act
      biosynthesis in wild-type cells. Overexpression of metK stimulated the expression
      of the pathway-specific regulatory gene actII-ORF4, as demonstrated by the RNase
      protection assay. The addition of SAM also caused hyperproduction of streptomycin
      in Streptomyces griseus. These findings implicate the significant involvement of
      intracellular SAM in initiating the onset of secondary metabolism in
      STREPTOMYCES:

PMID- 12511508
TI  - Global regulation of Staphylococcus aureus genes by Rot.
AB  - Staphylococcus aureus produces a wide array of cell surface and extracellular
      proteins involved in virulence. Expression of these virulence factors is tightly
      controlled by numerous regulatory loci, including agr, sar, sigB, sae, and arl,
      as well as by a number of proteins with homology to SarA. Rot (repressor of
      toxins), a SarA homologue, was previously identified in a library of transposon
      induced mutants created in an agr-negative strain by screening for restored
      protease and alpha-toxin. To date, all of the SarA homologues have been shown to
      act as global regulators of virulence genes. Therefore, we investigated the
      extent of transcriptional regulation of staphylococcal genes by Rot. We compared
      the transcriptional profile of a rot agr double mutant to that of its agr
      parental strain by using custom-made Affymetrix GeneChips. Our findings indicate
      that Rot is not only a repressor but a global regulator with both positive and
      negative effects on the expression of S. aureus genes. Our data also indicate
      that Rot and agr have opposing effects on select target genes. These results
      provide further insight into the role of Rot in the regulatory cascade of S.
      aureus virulence gene expression.

PMID- 12511509
TI  - Transcriptional analysis of the sfa determinant revealing mmRNA processing events
      in the biogenesis of S fimbriae in pathogenic Escherichia coli.
AB  - Among the virulence factors present in pathogenic extraintestinal Escherichia
      coli strains, expression of fimbrial adhesins is necessary for attachment to the
      host tissues and subsequent colonization. Occurrence of the sfa determinant
      coding for the S fimbriae is widespread among the uropathogens and meningitis
      isolates. The sfa operon consists of nine genes. In the biogenesis of S fimbriae,
      the proteins encoded by the sfa genes are presumably required in a specific
      stoichiometry. In the present work we studied how differential expression of the
      sfa operon genes occurs. Our findings indicate that a number of
      endoribonucleolytic cleavages occur in the mRNA from the sfa operon, and we
      detected the presence of different distinct transcriptional products, including
      sfaBA, sfaA, sfaADE, and sfaGSH. The sfaGSH transcript represents the three
      distal genes of the sfa operon, which code for the minor subunits of the S
      fimbriae. Analysis of the proteins in S fimbriae suggested that expression of the
      sfaGSH transcript provides equimolar amounts of the minor subunits. Furthermore,
      we showed that in the generation of the major sfaA transcript, the processing
      included RNase E endoribonuceolytic cleavage of the precursor sfaBA transcript.
      We suggest that posttranscriptional mRNA processing events result in differential
      gene expression important to achieve the stoichiometry necessary for fimbrial
      adhesin biogenesis.

PMID- 12511510
TI  - Escherichia coli cells with increased levels of DnaA and deficient in
      recombinational repair have decreased viability.
AB  - The dnaA operon of Escherichia coli contains the genes dnaA, dnaN, and recF
      encoding DnaA, beta clamp of DNA polymerase III holoenzyme, and RecF. When the
      DnaA concentration is raised, an increase in the number of DNA replication
      initiation events but a reduction in replication fork velocity occurs. Because
      DnaA is autoregulated, these results might be due to the inhibition of dnaN and
      recF expression. To test this, we examined the effects of increasing the
      intracellular concentrations of DnaA, beta clamp, and RecF, together and
      separately, on initiation, the rate of fork movement, and cell viability. The
      increased expression of one or more of the dnaA operon proteins had detrimental
      effects on the cell, except in the case of RecF expression. A shorter C period
      was not observed with increased expression of the beta clamp; in fact, many
      chromosomes did not complete replication in runout experiments. Increased
      expression of DnaA alone resulted in stalled replication forks, filamentation,
      and a decrease in viability. When the three proteins of the dnaA operon were
      simultaneously overexpressed, highly filamentous cells were observed (>50 micro
      m) with extremely low viability and, in runout experiments, most chromosomes had
      not completed replication. The possibility that recombinational repair was
      responsible for the survival of cells overexpressing DnaA was tested by using
      mutants in different recombinational repair pathways. The absence of RecA, RecB,
      RecC, or the proteins in the RuvABC complex caused an additional approximately
      100-fold drop in viability in cells with increased levels of DnaA, indicating a
      requirement for recombinational repair in these cells.

PMID- 12511511
TI  - Development of methicillin resistance in clinical isolates of Staphylococcus
      sciuri by transcriptional activation of the mecA homologue native to s.
AB  - The beta-lactam resistance gene mecA was acquired by Staphylococcus aureus from
      an extraspecies source. The search for the possible origin of this gene has led
      to the identification of a close structural homologue of mecA as a native gene in
      the animal species Staphylococcus sciuri. Surprisingly, the overwhelming majority
      of S. sciuri isolates were fully susceptible to beta-lactam antibiotics in spite
      of the ubiquitous presence of the mecA homologue in the bacteria. We now describe
      two unusual S. sciuri strains isolated from humans-SS-37 and SS-41-that showed
      resistance to methicillin associated with high rates of transcription of the mecA
      homologue and production of a protein resembling penicillin binding protein 2a,
      the gene product of S. aureus mecA. In strain SS-37 increased transcription of
      the mecA homologue was related to insertion of an IS256 element upstream of the
      structural gene, and strain SS-41 had single nucleotide alterations in the
      promoter region of the mecA homologue which appear to be related to up-regulation
      of the rate of transcription. A third methicillin-resistant human isolate of S.
      sciuri that carries both the native mecA homologue and a methicillin-resistant S.
      aureus (MRSA) type mecA, strain K3, was now shown to be unstable in the absence
      of drug selection, causing the segregation of antibiotic-susceptible cells
      accompanied by the loss of the MRSA type mecA. These observations illustrate the
      remarkable variety of strategies available to bacteria for acquiring mechanisms
      of drug resistance in the in vivo environment.

PMID- 12511512
TI  - A cka-gfp transcriptional fusion reveals that the colicin K activity gene is
      induced in only 3 percent of the population.
AB  - In prokaryotes, only a few examples of differential gene expression in cell
      populations have been described. Colicin production in natural populations of
      Escherichia coli, while providing a competitive advantage in the natural habitat,
      also leads to lysis of the toxin-producing cell. Colicin K synthesis has been
      found to be induced due to an increase in ppGpp (I. Kuhar, J. P. van Putten, D.
      Zgur-Bertok, W. Gaastra, and B. J. Jordi, Mol. Microbiol. 41:207-216). Using two
      transcriptional fusions, cka-gfp and cki-gfp, we show that at the single-cell
      level, the colicin K activity gene cka is expressed in only 3% of the bacterial
      population upon induction by nutrient starvation. In contrast, the immunity gene
      cki is expressed in the large majority of the cells. Expression of the cka-gfp
      fusion in a lexA-defective strain and in a relA spoT mutant strain indicates that
      differential expression of cka is established primarily at the level of
      transcription.

PMID- 12511513
TI  - Formation of an F' plasmid by recombination between imperfectly repeated
      chromosomal Rep sequences: a closer look at an old friend (F'(128) pro lac).
AB  - Plasmid F'(128) was formed by an exchange between chromosomal Rep sequences that
      placed lac near dinB between many pairs of Rep sequences. Plasmid F'(128) is
      critical for selection-enhanced lac reversion (adaptive mutation), which requires
      prior lac amplification. The structure of F'(128) supports the idea that
      amplification is initiated by Rep-Rep recombination and that general mutagenesis
      requires coamplification of dinB (error-prone polymerase) with lac.

PMID- 12511514
TI  - Flagella and Motility in Actinobacillus pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae has been considered nonmotile and nonflagellate.
      In this work, it is demonstrated that A. pleuropneumoniae produces flagella
      composed of a 65-kDa protein with an N-terminal amino acid sequence that shows
      100% identity with those of Escherichia coli, Salmonella, and Shigella
      flagellins. The DNA sequence obtained through PCR of the fliC gene in A.
      pleuropneumoniae showed considerable identity (93%) in its 5' and 3' ends with
      the DNA sequences of corresponding genes in E. coli, Salmonella enterica, and
      Shigella spp. The motility of A. pleuropneumoniae was observed in tryptic soy or
      brain heart infusion soft agar media, and it is influenced by temperature.
      Flagella and motility may be involved in the survival and pathogenesis of A.
      pleuropneumoniae in pigs.

PMID- 12511515
TI  - Novel methylotrophy genes of Methylobacterium extorquens AM1 identified by using
      transposon mutagenesis including a putative dihydromethanopterin reductase.
AB  - Ten novel methylotrophy genes of the facultative methylotroph Methylobacterium
      extorquens AM1 were identified from a transposon mutagenesis screen. One of these
      genes encodes a product having identity with dihydrofolate reductase (DHFR). This
      mutant has a C(1)-defective and methanol-sensitive phenotype that has previously
      only been observed for strains defective in tetrahydromethanopterin (H(4)MPT)
      dependent formaldehyde oxidation. These results suggest that this gene, dmrA, may
      encode dihydromethanopterin reductase, an activity analogous to that of DHFR that
      is required for the final step of H(4)MPT biosynthesis.

PMID- 12511516
TI  - Experimental verification of a sequence-based prediction: F(1)F(0)-type ATPase of
      Vibrio cholerae transports protons, not Na(+) ions.
AB  - The membrane energetics of the intestinal pathogen Vibrio cholerae involves both
      H(+) and Na(+) as coupling ions. The sequence of the c subunit of V. cholerae
      F(0)F(1) ATPase suggested that this enzyme is H(+) specific, in contrast to the
      results of previous studies on the Na(+)-dependent ATP synthesis in closely
      related Vibrio spp. Measurements of the pH gradient and membrane potential in
      membrane vesicles isolated from wild-type and DeltaatpE mutant V. cholerae show
      that the F(1)F(0) ATPase of V. cholerae is an H(+), not Na(+), pump, confirming
      the bioinformatics assignments that were based on the Na(+)-binding model of S.
      Rahlfs and V. Muller (FEBS Lett. 404:269-271, 1999). Application of this model to
      the AtpE sequences from other bacteria and archaea indicates that Na(+)-specific
      F(1)F(0) ATPases are present in a number of important bacterial pathogens.

PMID- 12511517
TI  - Identification of MpaA, an amidase in Escherichia coli that hydrolyzes the gamma
      D-glutamyl-meso-diaminopimelate bond in murein peptides.
AB  - MpaA amidase was identified in Escherichia coli by its amino acid sequence
      homology with the ENP1 endopeptidase from Bacillus sphaericus. The enzymatic
      activity of MpaA, i.e., hydrolysis of the gamma-D-glutamyl-diaminopimelic acid
      bond in the murein tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelic acid,
      was demonstrated in the cell extract of a strain expressing mpaA from a multicopy
      plasmid. An mpaA mpl (murein peptide ligase) double mutant accumulated large
      amounts of murein tripeptide in its cytoplasm, consistent with the premise that
      MpaA degrades the tripeptide if its recycling via the peptidoglycan biosynthetic
      pathway is blocked.

PMID- 12511518
TI  - ClpP of Streptococcus salivarius is a novel member of the dually regulated class
      of stress response genes in gram-positive bacteria.
AB  - Nucleotide sequence analysis of the Streptococcus salivarius clpP locus revealed
      potential binding sites for both the CtsR and HrcA repressors. Dual regulation by
      HrcA and CtsR was demonstrated by using Bacillus subtilis as a heterologous host,
      and CtsR was shown to bind directly to the clpP promoter sequence. This is the
      first example of a clpP gene under the control of HrcA.

PMID- 12511519
TI  - Isolation of a negative control mutant of the nitrogen assimilation control
      protein, NAC, in Klebsiella aerogenes.
AB  - A negative control mutant of the nitrogen assimilation control protein, NAC, has
      been isolated. Mutants with the leucine at position 111 changed to a
      nonhydrophobic residue activate transcription from hut and ure promoters, but
      fail to repress gdhA expression. This failure does not result from failure to
      bind to either of the two sites required for gdhA repression, but the binding at
      those sites is altered in the mutant. It appears that the NAC negative control
      mutants fail to form the complex structures (probably tetramers) formed by wild
      type NAC at the gdhA promoter.

PMID- 12511520
TI  - Polar targeting of DivIVA in Bacillus subtilis is not directly dependent on FtsZ
      or PBP 2B.
AB  - DivIVA is involved in Bacillus subtilis cell division and is located at the cell
      poles. Previous experiments suggested that the cell division proteins FtsZ and
      PBP 2B are required for polar targeting of DivIVA. By using outgrowing spores, we
      show that DivIVA accumulates at the cell poles independent of the presence of
      FtsZ or PBP 2B.

PMID- 12511522
TI  - Gene expression profiling in hypertension research: a critical perspective.
AB  - Recent advances in molecular biology and technology have made it possible to
      monitor the expression levels of virtually all genes simultaneously. As the tools
      for gene expression profiling have become more widely available, the number of
      investigators applying this technology in hypertension research, as in other
      fields of biomedical research, has grown rapidly. At the same time, numerous
      articles have been published that discuss the technical aspects of gene profiling
      and its promise for advancing research on the pathogenesis and treatment of
      multiple clinical disorders. However, much of the research carried out with gene
      expression profiling has been of a correlational or descriptive nature, and the
      true value of this technology is unclear. Despite the initial wave of enthusiasm
      for gene expression profiling, its actual utility for studying multifactorial
      disorders like hypertension remains to be established. In this review, we offer a
      critical perspective on the use of gene expression profiling in hypertension
      research and discuss some emerging strategies for taking this technology beyond
      the limits of correlational and descriptive studies.

PMID- 12511523
TI  - Angiotensinogen gene haplotype and hypertension: interaction with ACE gene I
      allele.
AB  - There are many reports demonstrating the association of renin-angiotensin system
      gene polymorphisms with hypertension in different populations. In the present
      study, we used haplotype analyses of the angiotensinogen gene with a new
      permutation-based hypothesis testing method to determine the association between
      multilocus angiotensinogen gene polymorphisms and hypertension in a relatively
      homogeneous Taiwanese population. We also genotyped angiotensin-converting enzyme
      gene insertion/deletion polymorphism and angiotensin II type 1-receptor gene
      A1166C polymorphism to detect epistatic gene-gene interactions. There were 408
      patients with hypertension (hypertensives) and 286 controls. The angiotensinogen
      gene haplotype frequencies were significantly different between hypertensives and
      controls, and this finding was only present in subjects with angiotensin
      converting enzyme gene II genotypes when the analysis was stratified by genotype
      of this polymorphism. In addition, the angiotensinogen gene haplotype structure
      of hypertensives was more heterogeneous than that of controls. Our results showed
      that angiotensinogen gene haplotypes were associated with hypertension and might
      act synergistically with I allele of the angiotensin-converting enzyme gene.

PMID- 12511524
TI  - TA repeat variation, Npr1 expression, and blood pressure: impact of the Ace
      locus.
AB  - The activity of the atrial natriuretic peptide receptor (Npr1) is altered in
      spontaneously hypertensive rats (SHR) in relation to its mRNA levels, suggesting
      abnormal transcriptional control in hypertension. A single-stranded
      conformational polymorphism caused by a repetitive dinucleotide segment of 10 TA
      in BN-Lx and of 40 TA in SHR was localized at position -943 relative to the
      transcription start site of the Npr1 gene, downstream of a putative cGMP
      regulatory region, and was the only sequence difference noted between the two
      strains. Transient transfections of -1520 to -920 Npr1 promoter-SV40-luciferase
      fusion vector showed that the construct from BN-Lx stimulated the SV40 promoter,
      whereas that from SHR slightly inhibited it. In contrast to the BN-Lx construct,
      the activity of the SHR fragment was refractory to downregulation by atrial
      natriuretic peptide. Genotype-phenotype correlation studies in recombinant inbred
      strains (RIS) derived from BN-Lx and SHR crosses revealed significant
      correlations of the TA repeat with basal guanylyl cyclase activity and Npr1 mRNA
      levels. The correlations were heightened by a locus on chromosome 10 containing
      the Ace gene. The highest basal guanylyl cyclase activity and Npr1 mRNA values
      were found in RIS with both genes (Npr1/Ace) of BN genotypes, whereas the lowest
      were recorded in RIS, with the SHR genotypes at both loci. This was inversely
      correlated with diastolic blood pressure in these strains. In conclusion, the
      longer TA repeat unit in the promoter of Npr1 of SHR, in tandem with a putative
      cGMP responsive element, regulates the transcription of the Npr1 gene with
      consequences on diastolic blood pressure.

PMID- 12511525
TI  - Angiotensinogen 235T allele "dosage" is associated with blood pressure
      phenotypes.
AB  - The genetic mechanisms underlying interindividual blood pressure variation among
      humans may reflect, at least in part, clustering of functional gene variants
      belonging to complex blood pressure control systems. In this study, we
      investigated the association of specific functional gene variants of the renin
      angiotensin system, ACE (I/D) and angiotensinogen (M/T) genes, with blood
      pressure phenotypes (systolic, mean, diastolic, and pulse pressure), in an
      ethnically mixed urban population in Brazil. Individuals (n=1421) were randomly
      selected from the general population of the Vitoria City Metropolitan area.
      Neither gender, age, smoking status, total cholesterol, triglycerides, HDL
      cholesterol, LDL-cholesterol, VLDL-cholesterol, or diabetes was associated with
      ACE or AGT polymorphism in univariate analysis. No association was found between
      ACE variants and blood pressure phenotypes. However, a statistically significant
      association was revealed between the AGT 235T variant and all blood pressure
      phenotypes, consistent with an additive/codominant mode of action even after
      adjustment for age and gender (P<0.01). Genotypic analysis contemplating both ACE
      and AGT variants in the same model did not show any significant interaction
      between both genetic polymorphisms. In addition, the AGT 235T allele was
      significantly associated with hypertension in a recessive model, which remained
      as an independent risk factor for hypertension even after adjustment for age,
      gender, and ethnicity (OR, 1.33; 95% CI, 1.04 to 1.70). Taken together, these
      data indicate a linear relation between AGT 235T allele number ("dosage") and
      blood pressure in an ethnically mixed urban population and confirmed its role as
      an independent risk factor for hypertension for men and women when in
      homozygosity.

PMID- 12511526
TI  - Angiotensin II receptor blockade: is there truly a benefit of adding an ACE
      inhibitor?
AB  - We assessed the blockade of the renin-angiotensin system (RAS) achieved with 2
      angiotensin (Ang) antagonists given either alone at different doses or with an
      ACE inhibitor. First, 20 normotensive subjects were randomly assigned to 100 mg
      OD losartan (LOS) or 80 mg OD telmisartan (TEL) for 1 week; during another week,
      the same doses of LOS and TEL were combined with 20 mg OD lisinopril. Then, 10
      subjects were randomly assigned to 200 mg OD LOS and 160 mg OD TEL for 1 week and
      100 mg BID LOS and 80 mg BID TEL during the second week. Blockade of the RAS was
      evaluated with the inhibition of the pressor effect of exogenous Ang I, an ex
      vivo receptor assay, and the changes in plasma Ang II. Trough blood pressure
      response to Ang I was blocked by 35+/-16% (mean+/-SD) with 100 mg OD LOS and by
      36+/-13% with 80 mg OD TEL. When combined with lisinopril, blockade was 76+/-7%
      with LOS and 79+/-9% with TEL. With 200 mg OD LOS, trough blockade was 54+/-14%,
      but with 100 mg BID it increased to 77+/-8% (P<0.01). Telmisartan (160 mg OD and
      80 mg BID) produced a comparable effect. Thus, at their maximal recommended
      doses, neither LOS nor TEL blocks the RAS for 24 hours; hence, the addition of an
      ACE inhibitor provides an additional blockade. A 24-hour blockade can be achieved
      with an angiotensin antagonist alone, provided higher doses or a BID regimen is
      used.

PMID- 12511527
TI  - Tissue-specific response to interstitial angiotensin II in humans.
AB  - Angiotensin II is synthesized locally in various tissues; however, the role of
      interstitial angiotensin II in the regulation of regional metabolism and tissue
      perfusion is not clear. We characterized the effect of interstially applied
      angiotensin II in skeletal muscle and subcutaneous adipose tissue of young,
      normal-weight, healthy subjects by using the microdialysis technique.
      Furthermore, we tested the hypothesis that the effect of interstitial angiotensin
      II is modulated by nitric oxide. Tissues were perfused with 0.01, 0.1, and 1
      micro mol/L angiotensin II in the presence of the L- or D-isomer of N(G)-nitro
      arginine-methyl ester (L- or D-NAME), the effective and noneffective isomer,
      respectively, for blocking nitric oxide synthase. Dialysate ethanol, glycerol,
      glucose, lactate, and pyruvate concentrations were measured to assess changes in
      blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively.
      Baseline blood flow and dialysate concentrations of the metabolites were similar
      with L- and D-NAME in both tissues. Blood flow and dialysate glucose and lactate
      did not change significantly in both tissues during perfusion with angiotensin
      II. Dialysate glycerol dose-dependently increased in adipose tissue (P<0.0438)
      but decreased in muscle (P<0.007). In muscle, dialysate pyruvate increased
      (P<0.0002), whereas lactate/pyruvate ratio decreased (P<0.001), both dose
      dependently. All effects were similar with L- and D-NAME and could be reversed by
      nitroprusside. We conclude that in contrast to the profound hemodynamic effect of
      intravascular angiotensin II, interstitial angiotensin II has a minimal acute
      effect on blood flow in both tissues. However, interstitial angiotensin II
      modulates lipid and carbohydrate metabolism in a tissue specific fashion. Thus,
      the physiology of interstitial angiotensin II cannot be predicted from
      intravascular studies.

PMID- 12511528
TI  - Urinary angiotensinogen as an indicator of intrarenal Angiotensin status in
      hypertension.
AB  - Angiotensin II (AngII) infusions augment renal angiotensinogen mRNA and protein
      and urinary angiotensinogen excretion (U(AGT)). Further experiments were
      performed in 4 groups of rats: normal salt diet with sham operation, NS+Sham,
      n=6; NS with AngII infusion at 40 ng/min via osmotic minipump, NS+AngII(40), n=9;
      NS with AngII infusion at 80 ng/min, NS+AngII(80), n=9; high-salt diet with
      deoxycorticosterone acetate salt pellet (100 mg), HS+DOCA, n=4. These experiments
      sought to determine whether enhanced U(AGT) is specifically associated with
      increased kidney AngII levels or is a nonspecific consequence of the
      hypertension. Systolic BP (SBP) was significantly increased to 131+/-2 and 162+/
      2 mm Hg at day 11 in NS+AngII(40) and NS+AngII(80), respectively, compared with
      NS+Sham (110+/-1). Regression analysis demonstrated a positive relationship
      (R=0.49) between SBP and U(AGT) for NS+Sham (1.1+/-0.3 nmol AngI/d), NS+AngII(40)
      (2.5+/-0.9), and NS+AngII(80) (5.5+/-1.5). U(AGT) was also highly correlated
      (R=0.70) with kidney AngII content for NS+Sham (49+/-6 fmol/g), NS+AngII(40)
      (215+/-49), and NS+AngII(80) (347+/-47); but not with plasma AngII (R=0.12).
      HS+DOCA rats also exhibited increased SBP to 134+/-1 mm Hg, but U(AGT) (1.4+/-0.4
      nmol AngI/d) and intrarenal AngII content (13+/-2 fmol/g) were not increased
      despite the hypertension. Infused human angiotensinogen could not be detected in
      urine of sham-operated or AngII-infused rats (n=4 each). These data demonstrate
      that U(AGT) increases in AngII-dependent hypertension in a dose- and time
      dependent manner, but not in hypertension elicited by HS+DOCA. The results
      support the hypothesis that AngII-dependent hypertension results in elevated
      intrarenal AngII and angiotensinogen levels, reflected by increased U(AGT), which
      does not occur in an AngII-independent hypertensive model.

PMID- 12511529
TI  - Cerebral arteriolar structure in mice overexpressing human renin and
      angiotensinogen.
AB  - We examined the hypothesis that the renin-angiotensin system plays an important
      role in vascular remodeling (defined as reduced external diameter) during chronic
      hypertension. We measured pressure, diameter, and cross-sectional area of the
      vessel wall in maximally dilated cerebral arterioles in transgenic mice that
      overexpress both human renin and human angiotensinogen and in spontaneously
      hypertensive mice, a model of chronic hypertension that is thought to develop
      independently of the renin-angiotensin system. Systemic arterial pressure under
      conscious conditions was increased by similar amounts in transgenically
      hypertensive mice (153+/-6 versus 117+/-4 mm Hg in controls; mean+/-SE, P<0.05)
      and spontaneously hypertensive mice (148+/-5 versus 112+/-5 mm Hg; P<0.05). The
      external diameter of maximally dilated cerebral arterioles was reduced in
      transgenically hypertensive mice (52+/-2 versus 66+/-3 micro m; P<0.05), but not
      in spontaneously hypertensive mice (58+/-4 versus 60+/-4 micro m; P>0.05). The
      cross-sectional area of the vessel wall was increased in both transgenically
      hypertensive mice (504+/-53 versus 379+/-37 microm2; P<0.05) and spontaneously
      hypertensive mice (488+/-40 versus 328+/-38 microm2; P<0.05). During maximal
      dilatation, the stress-strain curves in cerebral arterioles of transgenically
      hypertensive mice and spontaneously hypertensive mice were shifted to the right
      of the curves in corresponding controls, an indication that arteriolar
      distensibility was increased in the transgenically and spontaneously hypertensive
      groups. Thus, cerebral arterioles undergo remodeling and hypertrophy in
      transgenically hypertensive mice, but only hypertrophy in spontaneously
      hypertensive mice. These findings support the hypothesis that the renin
      angiotensin system is an important determinant of vascular remodeling during
      chronic hypertension.

PMID- 12511530
TI  - Modulation of angiotensin II responses in sympathetic neurons by cytosolic
      calcium.
AB  - Both stimulatory and suppressive responses of the sympathetic nervous system to
      angiotensin II (AII) have been reported in intact animals. To elucidate possible
      cellular mechanisms, we studied AII-induced changes in cytosolic Ca2+ ([Ca2+]i)
      in primary cultures of rat stellate ganglion neurons. Two different patterns of
      [Ca2+]i responses to AII were observed: dose-dependent increases in [Ca2+]i in
      cells with intrinsically low baseline [Ca2+]i (n=64) and dose-dependent
      suppression of [Ca2+]i in neurons with intrinsically higher baseline [Ca2+]i
      (n=46). Individual neurons could express both response patterns to AII. In
      neurons with low basal [Ca2+]i, superfusion with Ca2+ ionophore (ionomycin)
      increased [Ca2+]i and reversed the initial AII-induced stimulatory pattern. L
      type Ca2+ channel antagonism (nifedipine) in neurons with high baseline [Ca2+]i
      lowered [Ca2+]i and reversed the initial AII-induced suppressive response. Both
      stimulatory and suppressive responses were abolished by AT1 receptor antagonism
      (losartan). AII-induced stimulatory responses were blocked by IP3 receptor
      antagonism (2-APB) and by thapsigargin. AII-induced suppression of neuronal
      [Ca2+]i was blunted when Na-Ca exchange was impaired. We conclude that [Ca2+]i
      acts as a switch for AII-mediated stimulatory and suppressive responses in
      individual sympathetic neurons. AT1 receptor-mediated neuronal stimulation and
      suppression may allow local homeostatic adaptation to meet complex systemic
      needs.

PMID- 12511531
TI  - Effectiveness of aldosterone blockade in patients with diabetic nephropathy.
AB  - It has been reported that continuous ACE inhibitor therapy does not necessarily
      produce a maintained decrease in plasma aldosterone levels, which may remain high
      or increase eventually during long-term use (aldosterone escape). We have
      examined the role of aldosterone escape in 45 patients with type 2 diabetes and
      early nephropathy treated with an ACE inhibitor for 40 weeks. With treatment,
      there was a 40% reduction in average urinary albumin excretion, although urinary
      albumin excretion in patients with aldosterone escape (18 patients) was
      significantly higher than that in patients without escape (27 patients). In the
      18 patients with escape, spironolactone (25 mg/d) was added to ACE inhibitor
      treatment in 13. After a 24-week study period, urinary albumin excretion and left
      ventricular mass index were significantly reduced without blood pressure change.
      In conclusion, the present study demonstrates that aldosterone escape is observed
      in 40% of patients with type 2 diabetes with early nephropathy despite the use of
      ACE inhibitors. Our study suggests the possibility that aldosterone blockade may
      represent optimal therapy for patients with early diabetic nephropathy who show
      aldosterone escape during ACE inhibitor treatment and who no longer show maximal
      antiproteinuric effects of ACE inhibition. Additional, larger, prospectively
      randomized, double-blind studies will be needed before adaptation of this
      strategy.

PMID- 12511532
TI  - Maternal and paternal influences on left ventricular mass of offspring.
AB  - Significant intrafamilial correlations of left ventricular mass exist in first
      degree relatives. However, the specific maternal and paternal influences on left
      ventricular mass of offspring remain unknown. We therefore evaluated familial
      aggregation of left ventricular mass by type of familial relation in two European
      populations. A random sample of 159 nuclear families (250 parents and 321
      offspring) was investigated in Cracow, Poland, and Novosibirsk, Russia. The mean
      age of parents and offspring was 51.4 years and 25.1 years, respectively. Two
      dimensionally guided M-mode echocardiography was performed, and left ventricular
      mass was calculated. As a measure of concordance, we computed correlation
      coefficients for left ventricular mass between first-degree relatives and between
      spouse pairs. After adjustment for center, gender, age, height, body weight,
      systolic blood pressure, antihypertensive treatment, smoking, alcohol intake, and
      physical activity, the intrafamilial correlations for left ventricular mass were
      0.06 (P=0.57) in 91 spouse-spouse pairs, 0.14 (P=0.002) in 500 parent-offspring
      pairs, and 0.32 (P<0.001) in 179 sib-sib pairs. Across the four parent-offspring
      relations, the intrafamilial correlations of left ventricular mass differed. The
      mother-son (n=140, r=0.27, P<0.001) and mother-daughter (n=161, r=0.28, P<0.001)
      correlations were significant, whereas the father-son (n=101, r=0.04, P=0.69) and
      father-daughter (n=98, r=-0.09, P=0.38) correlations were not different from
      zero. Overall, the mother-offspring correlation coefficient was significantly
      higher than the father-offspring correlation (r=0.28 versus r=-0.04; P=0.005).
      Thus, maternal factors appear to have more impact on left ventricular mass of
      offspring than do paternal influences. Further studies are required to elucidate
      the genetic, epigenetic, and ecogenetic mechanisms underlying these divergent
      parent-offspring correlations.

PMID- 12511533
TI  - Echocardiographic wall motion abnormalities in hypertensive patients with
      electrocardiographic left ventricular hypertrophy: the LIFE Study.
AB  - There is limited information on correlates of left ventricular wall motion (WM)
      abnormalities in ambulatory patients with hypertension and ECG left ventricular
      hypertrophy by Cornell voltage-duration product and/or Sokolow-Lyon voltage
      criteria. Therefore, we assessed the prevalence and the correlates of
      echocardiographic global and segmental left ventricular WM abnormalities in 942
      hypertensive patients with hypertrophy enrolled in the Losartan Intervention For
      End-point reduction in hypertension (LIFE) echo substudy. Patients were separated
      into groups of those with normal WM or those with segmental or global WM
      abnormalities. Segmental and global WM abnormalities were mostly of mild degree
      and were detected in 7% and 6% of the study sample. Compared with subjects with
      normal motion, those with WM abnormalities were mostly men and had higher
      prevalences of self-reported coronary heart disease, ECG signs of myocardial
      infarction, ST-strain pattern, and higher Cornell voltage-duration product, echo
      left ventricular mass, and albuminuria, but lower total and high-density
      lipoprotein cholesterol. Blood pressure was similar among groups. No significant
      differences were found between patients with global or segmental WM
      abnormalities. Only half of patients with WM abnormalities had a history or ECG
      signs of coronary heart disease. Independent correlates of WM abnormalities were
      higher albuminuria and Cornell voltage-duration product, male gender, and echo
      left ventricular hypertrophy, but lower cholesterol. In a subanalysis restricted
      to patients with WM abnormalities, those with evident cardiovascular disease had
      a higher prevalence of ST-strain pattern than those with subclinical WM
      abnormalities, but other clinical, ECG, or echocardiographic parameters were
      indistinguishable between the 2 groups. Thus, in hypertensives with ECG left
      ventricular hypertrophy, WM abnormalities, mostly of mild degree, occurred in one
      eighth of the patients and were associated with male gender, left ventricular
      hypertrophy, and albuminuria. No significant differences were found between
      patients with global or segmental wall motion abnormalities.

PMID- 12511534
TI  - Myocardial fatty acid metabolism: independent predictor of left ventricular mass
      in hypertensive heart disease.
AB  - The expression of myocardial fatty acid beta-oxidation enzymes is downregulated
      at the gene transcriptional level in animal models of left ventricular
      hypertrophy and of heart failure. Humans with idiopathic dilated cardiomyopathy
      have decreased myocardial fatty acid oxidation. The extent to which molecular
      mechanisms, such as a reduction in myocardial fatty acid oxidation, regulate the
      cardiac hypertrophic response in humans in vivo is unknown. Positron emission
      tomography was used to measure myocardial blood flow, oxygen consumption, fatty
      acid utilization, and oxidation in two groups of patients: (1) hypertensive left
      ventricular hypertrophy (n=19; left ventricular mass, 211+/-39 g; left
      ventricular ejection fraction, 67+/-4%) and (2) left ventricular dysfunction
      (n=9; left ventricular mass, 210+/-36 g; left ventricular ejection fraction, 31+/
      10%); these were compared with a normal control group (n=36; left ventricular
      mass, 139+/-25 g; left ventricular ejection fraction, 66+/-6%). Left ventricular
      mass showed significant correlation with gender, diastolic and systolic blood
      pressure, myocardial fatty acid uptake, utilization and oxidation, myocardial
      blood flow, body mass index, and left ventricular ejection fraction (all P<0.02).
      Independent predictors of increased left ventricular mass were male gender
      (r=0.38, P<0.001), myocardial fatty acid oxidation (r=-0.24, P<0.018), systolic
      blood pressure (r=0.41, P<0.001), and left ventricular ejection fraction (r=
      0.29, P=0.005). Thus, myocardial fatty acid metabolism is an independent
      predictor of left ventricular mass in hypertension and in left ventricular
      dysfunction. The extent to which reduced myocardial fatty acid metabolism affects
      cardiovascular morbidity and mortality and whether pharmacologic modulation
      results in improved outcomes remains to be determined.

PMID- 12511535
TI  - Hepatocyte growth factor and left ventricular geometry in end-stage renal
      disease.
AB  - Hepatocyte growth factor is a pleiotropic cytokine with cardioprotective
      properties. Its serum concentration is markedly raised in end-stage renal
      disease. This study assessed the relation of hepatocyte growth factor (HGF) with
      left ventricular mass and geometry in end-stage renal disease. Serum HGF
      measurements and echocardiographic studies were performed in 185 patients
      receiving hemodialysis. Patients with serum HGF above the median (1.85 ng/mL) had
      more frequent cardiovascular complications. This cytokine was directly related to
      mean left ventricular wall thickness (r=0.23, P=0.002) and relative wall
      thickness (r=0.25, P=0.0001); a multivariate analysis showed that this relation
      was independent of other risk factors. Accordingly, the prevalence of left
      ventricular concentric geometry (either concentric left ventricular hypertrophy
      or remodeling) was much higher (n=49, 53%) among patients with HGF values above
      the median that in those with values < or =1.85 ng/mL (n=31, 34%). Furthermore,
      the risk for left ventricular concentric geometry was higher in patients with HGF
      values above the median (odds ratio, 2.57; 95% CI, 1.33 to 4.98; P=0.005), and
      multiple logistic regression analysis confirmed that this association was
      independent of other risk factors. In patients receiving hemodialysis, elevated
      serum HGF is associated with concentric left ventricular geometry. This is
      consistent with reports that link this cytokine to arterial remodeling and
      survival in patients with end-stage renal disease and suggests that it is part of
      a counterregulatory response aimed at attenuating cardiovascular damage in this
      high-risk population.

PMID- 12511536
TI  - Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat
      hearts.
AB  - Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it
      also has effects on contractility. The interaction of endothelin-1 and the Frank
      Starling response is unknown. The present study aimed to characterize the role of
      endothelin-1 in the regulation of the Frank-Starling response, one of the major
      mechanisms regulating cardiac contractile force, in both normal and hypertrophied
      hearts. Nontransgenic rat hearts and hypertrophic hearts of hypertensive double
      transgenic rats harboring human angiotensinogen and renin genes were studied in a
      Langendorff isolated heart setup with a liquid-filled balloon inside the left
      ventricle used to measure contractile parameters. The rats were studied at
      compensated phase, before showing any signs of heart failure. Compensated
      hypertrophy in double transgenic rat hearts resulted in improved contractility at
      a given level of preload when compared with nontransgenic rat hearts. Hearts of
      both rat lines showed preserved Frank-Starling responses, that is, increased
      contractile function in response to increased end-diastolic pressure. The mixed
      endothelin A/B receptor antagonist bosentan attenuated the Frank-Starling
      response by 53% (P<0.01) in the double transgenic hearts but not in nontransgenic
      hearts. The diastolic parameters remained unaffected. The left ventricles of the
      double transgenic rat hearts showed an 82% higher level of endothelin type A
      receptor mRNA and a 25% higher level of immunoreactive endothelin-1 compared with
      nontransgenic rat hearts. The type 1 angiotensin II receptor antagonist CV-11974
      had no significant effect on contractile function in response to load in either
      strain. These results show that endogenous endothelin-1 contributes to the Frank
      Starling response in hypertrophied rat hearts by affecting systolic performance.

PMID- 12511537
TI  - Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits
      fibrosis.
AB  - We have previously demonstrated that stimulation of the angiotensin (Ang) II type
      2 receptor in vascular smooth muscle cells caused bradykinin production by
      activating kininogenase in transgenic mice. The aim of this study was to
      determine whether overexpression of AT2 receptors in cardiomyocytes attenuates
      Ang II-induced cardiomyocyte hypertrophy or interstitial fibrosis through a
      kinin/nitric oxide (NO)-dependent mechanism in mice. Ang II (1.4 mg/kg per day)
      or vehicle was subcutaneously infused into transgenic mice and wild-type mice for
      14 days. The amount of cardiac AT2 receptor relative to AT1 receptor in
      transgenic mice was 22% to 37%. Ang II caused similar elevations in systolic
      blood pressure (by approximately 45 mm Hg) in transgenic mice and wild-type mice.
      Myocyte hypertrophy assessed by an increase in myocyte cross-sectional area, left
      ventricular mass, and atrial natriuretic peptide mRNA levels were similar in
      transgenic and wild-type mice. Ang II induced prominent perivascular fibrosis of
      the intramuscular coronary arteries, the extent of which was significantly less
      in transgenic mice than in wild-type mice. Inhibition of perivascular fibrosis in
      transgenic mice was abolished by cotreatment with HOE140, a bradykinin B2
      receptor antagonist, or L-NAME, an inhibitor of NO synthase. Cardiac kininogenase
      activity was markedly increased (approximately 2.6-fold, P<0.001) after Ang II
      infusion in transgenic mice but not in wild-type mice. Immunohistochemistry
      indicated that both bradykinin B2 receptors and endothelial NO synthase were
      expressed in the vascular endothelium, whereas only B2 receptors were present in
      fibroblasts. These results suggest that stimulation of AT2 receptors present in
      cardiomyocytes attenuates perivascular fibrosis by a kinin/NO-dependent
      mechanism. However, the effect on the development of cardiomyocyte hypertrophy
      was not detected in this experimental setting.

PMID- 12511538
TI  - Asymmetry of renal blood flow in patients with moderate to severe hypertension.
AB  - It is generally assumed that renal blood flow is symmetric in the absence of
      renal artery stenosis. The aim of the present study was to evaluate whether this
      is really the case. From a group of consecutive hypertensive patients who had
      undergone renal angiography, we selected those with patent renal arteries. In all
      of them selective renal blood flow (RBF) measurements (133Xenon washout
      technique) had been performed with blood sampling from aorta and both renal veins
      (n=148). Asymmetry of RBF, defined as > or =25% difference in RBF between left
      and right kidney, was present in 51% of the patients. Subjects with and without
      asymmetry did not differ in age, body mass index, blood pressure, creatinine
      clearance, renal volume, or activity of the renin-angiotensin system. The
      presence of asymmetry coincided with an increased rate of false-positive results
      on renal scintigraphy. Preliminary data suggest that there may be a relation
      between asymmetry and renal sympathetic nerve activity. This study demonstrates
      that asymmetry of RBF is a frequent finding in essential hypertension, which may
      confound the results of diagnostic tests for renal artery stenosis. Furthermore,
      the present results underscore the importance of studying the function of both
      kidneys separately, because it cannot be assumed that they are functionally
      equal.

PMID- 12511539
TI  - Phase-contrast magnetic resonance flow quantification in renal arteries:
      comparison with 133Xenon washout measurements.
AB  - To assess the accuracy of 2D phase-contrast magnetic resonance (2D PC MR) renal
      artery flow measurements, data obtained with this technique were compared with
      those acquired with the 133Xenon-washout procedure. In addition, the 2D PC MR
      flow data were related to functional renal information as derived from selective
      arterial and venous renin sampling. In 53 patients suspected of having
      renovascular hypertension, MR angiography of the renal arteries was performed,
      followed by a 3-step angiographic procedure: (1) selective venous and arterial
      renin sampling; (2) assessment of the renal blood flow by means of the 133Xenon
      washout technique, and (3) conventional renal angiography. After initial
      assessment, 71 kidneys were left for analysis. The overall prevalence of
      renovascular disease > or =50% stenosis was 18%. Mean renal blood flow as
      assessed with the 2D PC MR technique showed a significant correlation with the
      133Xenon washout flow measurements, with a Pearson correlation coefficient of
      0.69 (2-tailed; P<0.01). PC MR blood flow measurements correlated poorly with the
      presence and/or severity of renovascular disease on conventional angiography
      (r=0.1, P=0.36). Likewise, no statistically significant correlation with either
      renal venous renin levels or the renin ratio could be identified. Measurement of
      renal artery blood flow with the use of a 2D PC MR technique is technically
      feasible. However, the mean renal artery blood flow correlates poorly with either
      the presence of renovascular disease on angiography or with renin levels. Further
      improvement of this technique is necessary before it can be applied on a larger
      scale.

PMID- 12511540
TI  - Does brain natriuretic peptide have a direct renal effect in human hypertensives?
AB  - Systemic infusion of brain natriuretic peptide (BNP) stimulates natriuresis and
      diuresis but has variable effects on the renal vasculature. In this study, we
      investigated whether BNP has any direct effects on the kidney in hypertensive
      patients. Three stepwise increasing doses of BNP (60, 120, and 180 pmol/min) or
      placebo were infused into the renal artery of 26 hypertensive patients. Renal
      blood flow was determined with the 133Xenon washout technique. Before and after
      infusion of BNP, arterial and venous blood samples were taken for cGMP, renin,
      and creatinine concentration. Intra-arterial blood pressure and heart rate were
      monitored continuously. Intrarenal BNP infusion did not induce significant
      changes in renal blood flow despite increases in circulating levels of cGMP. The
      latter, however, was not associated with changes in the cGMP gradient across the
      kidney. In addition, we did not find any BNP-related changes in the secretion of
      active renin and in creatinine extraction. At the highest dose, heart rate
      increased after BNP infusion without a change in mean intra-arterial blood
      pressure. In conclusion, this study suggests that at least in hypertensive
      subjects, BNP has no direct intrarenal hemodynamic effects and that the rise in
      circulating cGMP without changes in net renal extraction of this second messenger
      is related to a primary extrarenal target of BNP.

PMID- 12511541
TI  - G protein beta3 gene variant, vascular function, and insulin sensitivity in type
      2 diabetes.
AB  - A common polymorphism (825 C/T) in exon 10 of the GNB3 gene, that encodes for the
      beta-3 subunit, has been associated with different degrees of activation of
      heterotrimeric guanine nucleotide binding proteins (G proteins). Many hormones
      and neurotransmitters use specific receptors that interact noncovalently with G
      proteins in the transmembrane signaling process. Among them, insulin uses an
      inhibitory G protein-sensitive mechanism that is involved in metabolic and
      vascular events, leading to enhanced glucose transport and vasodilation. We
      hypothesized differences in peripheral and vascular insulin sensitivity according
      to GNB3 gene polymorphism in type 2 diabetic patients. To address this issue, we
      used an intervention-optimization protocol to examine whether diabetic patients
      with the variant show a different response in terms of insulin-sensitivity.
      Interindividual differences in baseline insulin sensitivity and vascular
      dysfunction (vasodilatory response to glyceryl trinitrate) were not attributable
      to this polymorphism of the GNB3 gene. However, in contrast to normal
      homozygotes, insulin sensitivity (S(I)) significantly improved (P=0.01) in
      carriers of the 825T variant. Parallel to these findings, stimulated C-peptide
      tended to decrease, and the response to glyceryl trinitrate significantly
      improved (P=0.004) among 825T carriers. Body mass index, systolic and diastolic
      blood pressure, heart rate, or serum lipid levels did not significantly change in
      either group. Our findings suggest an effect of GNB3 gene polymorphism on
      important phenotypic variations in type 2 diabetes mellitus. The GNB3 gene
      polymorphism might be an example of pharmacogenetics, with the underlying
      etiological genetic defect altering the response to treatment.

PMID- 12511542
TI  - Greater age-related reductions in central arterial compliance in resistance
      trained men.
AB  - Reductions in the compliance of central arteries exert a number of adverse
      effects on systemic cardiovascular function and disease risk. Using the cross
      sectional study design, we determined the relation between chronic resistance
      training and carotid arterial compliance. A total of 62 healthy normotensive men,
      20 to 39 years of age (young) and 40 to 60 years of age (middle-aged), who were
      either sedentary or resistance-trained, were studied. In both activity groups,
      carotid arterial compliance (simultaneous ultrasound and applanation tonometry)
      was lower (P<0.05) in the middle-aged compared with the young men. There was no
      significant difference between young sedentary and resistance-trained men. In the
      middle-aged group, carotid arterial compliance in the resistance-trained men was
      approximately 30% lower (P<0.01) than their sedentary peers. Femoral artery
      compliance and arm pulse wave velocity (measures of peripheral artery stiffness)
      were not different among any groups. Left ventricular hypertrophy index
      (echocardiography) was greater (P<0.05) in resistance-trained compared with
      sedentary men and was associated with carotid arterial compliance (r=-0.35;
      P<0.01). We concluded that (1) resistance training is associated with the smaller
      central arterial compliance in healthy middle-aged men; (2) age-related
      reductions in arterial compliance was greater in resistance-trained men than in
      sedentary men; and (3) the lower arterial compliance in the resistance-trained
      men is associated with left ventricular hypertrophy. In marked contrast to the
      beneficial effect of regular aerobic exercise, the present findings are not
      consistent with the idea that resistance training exerts beneficial influences on
      arterial wall buffering functions.

PMID- 12511543
TI  - Specific potentiation of endothelium-dependent contractions in SHR by
      tetrahydrobiopterin.
AB  - This study was designed to determine the effect of pteridines, R- and S
      tetrahydrobiopterin, sepiapterin, and dihydrobiopterin on endothelium-dependent
      contractions to acetylcholine in isolated aortas from spontaneously hypertensive
      rat and normotensive Wistar-Kyoto rat. The noncumulative addition of redox-active
      pteridines R- and S-tetrahydrobiopterin (but not the oxidized analogues
      sepiapterin and dihydrobiopterin) produced a concentration-dependent transient
      contraction in isolated aortic rings from both normotensive and hypertensive
      rats. R- and S-tetrahydrobiopterin (but not sepiapterin or dihydrobiopterin)
      potentiated the endothelium-dependent contractions to acetylcholine but only in
      aortas from hypertensive rats and in the presence of N(G)-nitro-L-arginine. In
      these aortas, the generation of oxygen-derived free radicals by the combination
      of xanthine plus xanthine oxidase also potentiated the endothelium-dependent
      contractions to acetylcholine. The presence of R-tetrahydrobiopterin did not
      alter the characteristics of the endothelium-dependent contractions because they
      were inhibited by valeryl salicylate, an inhibitor of cyclooxygenase-1, by
      S18886, a TP-receptor antagonist or by Tiron, a cell permeable superoxide anion
      scavenger. However, the contractions to acetylcholine, which are unaffected by
      the combination of superoxide dismutase and catalase, become significantly
      inhibited by these two scavengers in the presence of R-tetrahydrobiopterin. In
      the presence of N(G)-nitro-L-arginine, R-tetrahydrobiopterin did not affect the
      contractions to phenylephrine, U 46619, or to oxygen-derived free radicals
      generated by xanthine plus xanthine oxidase. These results indicate that the
      production of superoxide by the autoxidation of tetrahydrobiopterin selectively
      enhances endothelium-dependent contractions in the spontaneously hypertensive rat
      when nitric oxide synthase is inhibited.

PMID- 12511544
TI  - A diffusible substance(s) mediates endothelium-dependent contractions in the
      aorta of SHR.
AB  - A modified bioassay system was designed to demonstrate the diffusible nature of
      endothelium-derived contracting factor(s) released by acetylcholine in the aorta
      of spontaneously hypertensive rat. In "sandwich"-like layered preparation,
      isometric tension was recorded from a bioassay strip (without endothelium) in the
      presence of N(G)-nitro-L-arginine and tetrahydrobiopterin to selectively
      potentiate endothelium-dependent contractions. A donor strip (with or without
      endothelium) was stitched on the bioassay tissue so that it did not directly
      contribute to the recorded contractions. Acetylcholine induced contractions that
      occurred only when the donor strip was with endothelium. Superoxide dismutase did
      not affect but catalase and the combination of superoxide dismutase plus catalase
      significantly decreased the endothelium-dependent contraction. The contractions
      in the layered preparations were abolished when the donor strip with endothelium
      was treated previously with valeryl salicylate, an irreversible cyclooxygenase-1
      inhibitor, but remained unaffected when the bioassay strip was treated with the
      compound. Previous treatment of the bioassay strip alone with S 18886 abolished
      the contractile response, whereas treatment of the donor strip with endothelium
      by the selective TP receptor antagonist only produced a moderate inhibition.
      These results indicate that in the aorta of spontaneously hypertensive rats,
      endothelium-dependent contractions to acetylcholine involve a diffusible
      substance(s) released by the endothelium. The production of this contracting
      factor(s) requires the activation of endothelial cyclooxygenase-1, and its action
      the activation of TP receptors on the vascular smooth muscle cells.

PMID- 12511545
TI  - Heme oxygenase inhibitor restores arteriolar nitric oxide function in dahl rats.
AB  - Vascular tissues express heme oxygenase (HO), which metabolizes heme to form
      carbon monoxide (CO). CO relaxes vascular smooth muscle but inhibits nitric oxide
      (NO) formation. Decreased NO synthesis may contribute to salt-induced
      hypertension in Dahl salt-sensitive (DS) rats. The current study examines the
      hypothesis that elevated levels of endogenous CO contribute to NO dysfunction in
      salt-induced hypertensive DS rats. Male DS rats were placed on high-salt (8%
      NaCl, HS) or low-salt (0.3% NaCl, LS) diets for 4 weeks. With respect to the LS
      group, the HS group's blood pressure and carboxyhemoglobin levels were elevated,
      and abdominal aortas showed 6-fold higher HO-1 protein levels. Experiments used
      isolated pressurized first-order gracilis muscle arterioles superfused with
      oxygenated modified Krebs buffer. An inhibitor of NO synthase, Nomega-nitro-L
      arginine methyl ester (L-NAME), caused concentration-dependent vasoconstriction
      in both groups, with attenuated responses in HS arterioles. HS arterioles also
      showed attenuated vasodilatory responses to an endothelium-dependent vasodilator,
      acetylcholine. Acute pretreatment with an inhibitor of HO, chromium
      mesoporphyrin, enhanced vascular responses to L-NAME and acetylcholine in both
      groups but abolished the differences between HS and LS arterioles. These data
      show that HO-1 protein levels and CO production are increased in HS rats.
      Arteriolar responses to L-NAME and acetylcholine are impaired in HS rats compared
      with LS animals, and this difference can be abolished by an inhibitor of
      endogenous CO production. These results suggest that elevated levels of
      endogenous CO contribute to arteriolar NO dysfunction in DS rats with salt
      induced hypertension.

PMID- 12511546
TI  - Enhancement of ischemia-induced angiogenesis by eNOS overexpression.
AB  - It remains undetermined whether continuous endothelial nitric oxide (NO)
      overexpression exerts angiogenic action. We surgically induced hindlimb ischemia
      in transgenic mice overexpressing endothelial NO synthase in the endothelium
      (eNOS-Tg) and studied neocapillary formation, ischemia-induced vascular
      endothelial growth factor (VEGF) expression, cGMP accumulation, and Akt/PKB
      signaling. Laser Doppler imaging revealed a markedly increased recovery of blood
      perfusion in ischemic limbs of eNOS-Tg mice (44% increase) compared with that in
      wild-type mice. Angiography showed a marked increase in basal and ischemia
      induced collateral vessel formation in eNOS-Tg mice. Basal capillary densities
      and tissue cGMP levels were increased in eNOS-Tg mice (1.8-fold and 1.6-fold
      versus wild-type mice, respectively). Ischemia-induced neocapillary formation and
      cGMP accumulation were markedly increased in eNOS-Tg mice (3.6-fold and 4.1-fold
      versus preischemia levels, respectively), whereas those in wild-type mice were
      much less (1.8-fold and 1.5-fold, respectively). Basal and time-dependent VEGF
      expression in ischemic muscles did not differ between eNOS-Tg and wild-type mice.
      Basal and VEGF-mediated Akt phosphorylation in aortas was similar between eNOS-Tg
      and wild-type mice. Aortic basal eNOS expression was increased 3.3-fold, and VEGF
      mediated eNOS phosphorylation was markedly induced in aortas of eNOS-Tg compared
      with preischemia levels (4.2-fold), whereas much smaller changes were observed in
      wild-type mice (1.8-fold increase). Our study demonstrates that overexpression of
      eNOS protein causes a marked increase in neocapillary formation in response to
      tissue ischemia without affecting ischemia-induced VEGF expression or VEGF
      mediated Akt phosphorylation.

PMID- 12511547
TI  - Association of endothelin-1 gene variant with hypertension.
AB  - Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial
      and smooth muscle cells. Many lines of biological evidence suggest that the ET-1
      gene is a candidate gene for hypertension. Moreover, recent association studies
      suggested that a G/T polymorphism with an amino acid substitution (Lys/Asn) at
      codon 198 in exon 5 of the ET-1 gene interacts with body mass index (BMI) in
      association with blood pressure. They suggested that T carriers are more
      sensitive to weight gain than GG homozygotes in association with blood pressure.
      However, association studies are often irreproducible, and the first study often
      suggests a stronger genetic effect than is found by subsequent studies. We
      therefore assessed the interaction in 2 large Japanese populations. The present
      study showed a nonsignificant but similar trend to the results of previous
      reports. Moreover, in line with previous reports, this study revealed a
      significant interaction between the ET-1 K198N (G/T) polymorphism and BMI in
      association with hypertension in our populations (P=0.027). The interaction was
      significant, even after adjustment for gender and age (P=0.045) and for all
      confounding factors (P=0.044). T carriers were more sensitive to weight gain than
      GG homozygotes in association with hypertension. Considering the combined impact
      of obesity and hypertension on the development of cardiovascular and
      cerebrovascular disorders, T allele carriers might represent elective targets for
      therapy to lower their body weight.

PMID- 12511548
TI  - Gender-linked hypertension in offspring of lard-fed pregnant rats.
AB  - Epidemiological studies suggest an association between maternal nutrition and
      offspring cardiovascular disease. We previously demonstrated endothelial
      dysfunction and abnormal aortic fatty acid composition in adult female offspring
      of rats fed animal lard during pregnancy. We have now further investigated this
      model. Female Sprague-Dawley rats were fed a control breeding diet (5.3% fat) or
      a diet rich in lard (25.7% fat) 10 days before and throughout pregnancy and
      lactation. Male and female offspring were implanted with radiotelemeters for
      recording of blood pressure, heart rate, and activity at 80, 180, and 360 days of
      age. Reactivity to acetylcholine and to nitric oxide were assessed in isolated
      small mesenteric arteries from 80- and 180-day-old littermates. Systolic blood
      pressure (awake phase) was raised in female offspring (180 days: offspring of
      control, 130.7+/-1.6 mm Hg, n=5, versus offspring of lard-fed, 138.1+/-2.9, n=5,
      P=0.029; 360 days: offspring of control, 129.7+/-3.7 mm Hg, n=6, versus offspring
      of lard-fed, 142.1+/-3.2, n=6, P=0.005). Diastolic blood pressure was also raised
      at 180 days (offspring of control, 87.6+/-1.0 mm Hg, n=5, versus offspring of
      lard-fed, 94.7+/-2.6, n=5, P=0.011). Blood pressure was not raised in male
      offspring. Endothelium-dependent relaxation to acetylcholine was blunted in male
      and female offspring of lard-fed dams (80 and 180 days). Feeding a diet rich in
      lard to pregnant rats leads to gender-related cardiovascular dysfunction in
      normally fed offspring.

PMID- 12511549
TI  - Alteration of lipids, G proteins, and PKC in cell membranes of elderly
      hypertensives.
AB  - In this study, we quantified the levels of lipids and signaling proteins in
      erythrocyte membranes from elderly normotensive and hypertensive subjects. In
      hypertensive subjects, the cholesterol/phospholipid ratio increased significantly
      in erythrocyte membranes, owing to the reduction of phospholipid levels
      concomitant with a rise in the levels of cholesterol. In addition, differences
      were also found in the amount of fatty acids in both phospholipid and cholesterol
      esters. Erythrocyte membranes from hypertensive subjects contained higher levels
      of monounsaturated and lower levels of polyunsaturated fatty acids. On the other
      hand, signaling proteins such as G proteins and protein kinase C have been
      implicated in the control of blood pressure. Previous studies have shown that the
      cellular localization and the activity of these proteins are modulated by the
      type and the abundance of membrane lipids. For this reason, we assessed the
      levels of these signaling molecules in the membrane. We found that the levels of
      membrane-associated (active/preactive) G proteins (Galpha(i), Galpha(o), and
      Gbeta) and protein kinase C were significantly reduced in hypertensive subjects.
      We believe that these alterations could be related to the etiopathology of
      hypertension in elderly subjects or alternatively may correspond to adaptive
      compensatory mechanisms.

PMID- 12511550
TI  - Effect of smoking on arterial stiffness and pulse pressure amplification.
AB  - The brachial artery pressure waveform is abnormal in smokers, but the effect of
      smoking on the aortic pressure waveform in both smokers and nonsmokers,
      particularly in the younger population, is unknown. We compared the acute and
      chronic effects of smoking on large-artery properties in 185 healthy young
      smokers and nonsmokers (mean+/-SD, 22+/-5 years). We matched 41 chronic smokers
      for age, height, weight, and gender with 116 nonsmokers. The augmentation index,
      a measure of arterial wave reflection in the aorta, was measured by applanation
      tonometry (Sphygmocor). We also compared augmentation index, aortic pulse wave
      velocity (Complior), and blood pressure in 28 subjects (11 chronic smokers)
      before and for 15 minutes after smoking 1 cigarette (nicotine content, 1.2 mg).
      Although brachial blood pressure was not different, the aortic systolic blood
      pressure (101+/-8 versus 97+/-9 mm Hg) and augmentation index (0.7+/-13 versus 
      5.7+/-14) were higher (P<0.01) in chronic smokers than in nonsmokers, whereas
      aortic-brachial pulse pressure amplification was reduced (13.7+/-8 versus 17.7+/
      5 mm Hg, P<0.01). These effects were seen in both male and female subjects.
      Acutely in both groups, smoking significantly increased (P<0.01) both brachial
      and aortic blood pressure, augmentation index, and pulse wave velocity. No
      changes were seen after sham smoking. This study shows an acute increase in
      arterial stiffness after smoking 1 cigarette in chronic smokers and nonsmokers.
      Higher aortic systolic blood pressure and greater arterial stiffness, in part due
      to reduced pulse pressure amplification and increased arterial wave reflection,
      suggest that the adverse hemodynamic effects have hitherto been underestimated in
      young chronic smokers.

PMID- 12511551
TI  - Role of protein kinase CK2 phosphorylation in the molecular chaperone activity of
      nucleolar protein b23.
AB  - Protein B23 is a multifunctional nucleolar protein whose molecular chaperone
      activity is proposed to play role in ribosome assembly. Previous studies
      (Szebeni, A., and Olson, M. O. J. (1999) Protein Sci. 8, 905-912) showed that
      protein B23 has several characteristics typical of molecular chaperones,
      including anti-aggregation activity, promoting the renaturation of denatured
      proteins, and preferential binding to denatured substrates. However, until now
      there has been no proposed mechanism for release of a bound substrate. Protein
      B23 can be phosphorylated by protein kinase CK2 (CK2) in a segment required for
      chaperone activity. The presence of bound substrate enhanced the rate of CK2
      phosphorylation of protein B23 by 2-3-fold, and this enhancement was dependent on
      a nonpolar region in its N-terminal end. Formation of a complex between B23 and
      chaperone test substrates (rhodanese or citrate synthase) was inhibited by CK2
      phosphorylation. Furthermore, CK2 phosphorylation of a previously formed B23
      substrate complex promoted its dissociation. The dissociation of complexes
      between B23 and the human immunodeficiency virus-Rev protein required both CK2
      phosphorylation and competition with a Rev nuclear localization signal peptide,
      suggesting that Rev binds B23 at two separate sites. These studies suggest that
      unlike many molecular chaperones, which directly hydrolyze ATP, substrate release
      by protein B23 is dependent on its phosphorylation by CK2.

PMID- 12511552
TI  - Solution structure and dynamics of a calcium binding epidermal growth factor-like
      domain pair from the neonatal region of human fibrillin-1.
AB  - Fibrillin-1 is a mosaic protein mainly composed of 43 calcium binding epidermal
      growth factor-like (cbEGF) domains arranged as multiple, tandem repeats.
      Mutations within the fibrillin-1 gene cause Marfan syndrome (MFS), a heritable
      disease of connective tissue. More than 60% of MFS-causing mutations identified
      are localized to cbEGFs, emphasizing that the native properties of these domains
      are critical for fibrillin-1 function. The cbEGF12-13 domain pair is within the
      longest run of cbEGFs, and many mutations that cluster in this region are
      associated with severe, neonatal MFS. The NMR solution structure of Ca(2+)-loaded
      cbEGF12-13 exhibits a near-linear, rod-like arrangement of domains. This
      observation supports the hypothesis that all fibrillin-1 (cb)EGF-cbEGF pairs,
      characterized by a single interdomain linker residue, possess this rod-like
      structure. The domain arrangement of cbEGF12-13 is stabilized by additional
      interdomain packing interactions to those observed for cbEGF32-33, which may help
      to explain the previously reported higher calcium binding affinity of cbEGF13.
      Based on this structure, a model of cbEGF11-15 that encompasses all known
      neonatal MFS missense mutations has highlighted a potential binding region.
      Backbone dynamics data confirm the extended structure of cbEGF12-13 and lend
      support to the hypothesis that a correlation exists between backbone flexibility
      and cbEGF domain calcium affinity. These results provide important insight into
      the potential consequences of MFS-associated mutations for the assembly and
      biomechanical properties of connective tissue microfibrils.

PMID- 12511553
TI  - Fibrates down-regulate hepatic scavenger receptor class B type I protein
      expression in mice.
AB  - Fibrates are normolipidemic drugs used in atherogenic dyslipidemia because of
      their ability to raise high density lipoprotein (HDL) and decrease triglyceride
      levels. They exert multiple effects on lipid metabolism by activating the
      peroxisome proliferator-activated receptor-alpha (PPAR-alpha), which controls the
      transcriptional regulation of genes involved in hepatic fatty acid, cholesterol,
      and lipoprotein metabolism. The hepatic expression of the scavenger receptor
      class B type I (SR-BI) plays a critical role in lipoprotein metabolism, mainly
      due to its ability to mediate selective cholesterol uptake. Because fibrates and
      PPAR-alpha agonists up-regulate SR-BI expression in human and murine macrophages,
      we tested whether fibrates raised a similar regulatory response on hepatic SR-BI
      expression in mice. Surprisingly, fibrate treatment suppressed SR-BI protein
      expression in the liver without changing steady state SR-BI mRNA levels.
      Decreased hepatic SR-BI protein expression correlated with enlarged HDL particle
      size. This effect was concomitant with down-regulation of CLAMP, a putative SR-BI
      stabilizing protein found in the hepatic plasma membrane, which was also not
      associated to changes in CLAMP mRNA levels. The post-transcriptional regulatory
      effect of fibrates over hepatic SR-BI protein levels was dependent on PPAR-alpha
      expression, because it was absent in PPAR-alpha-deficient mice. Restoring hepatic
      SR-BI expression in fibrate-treated mice by recombinant adenoviral gene transfer
      abolished fibrate-mediated HDL particle size enlargement. This study describes a
      novel effect of fibrates on hepatic SR-BI expression providing an alternative
      mechanism by which this drug family modulates HDL metabolism in vivo.

PMID- 12511554
TI  - Src family kinases are involved in the differential signaling from two splice
      forms of c-Kit.
AB  - In both mice and humans alternate splicing results in isoforms of c-Kit
      characterized by the presence or the absence of a tetrapeptide sequence, GNNK, in
      the juxtamembrane region of the extracellular domain. Dramatic differences in the
      kinetics and magnitude of activation of the intrinsic tyrosine kinase activity of
      c-Kit between the GNNK- and GNNK+ isoforms has previously been shown. Here we
      report the analysis of downstream targets of receptor signaling, which revealed
      that the signaling was differentially regulated in the two splice forms. The
      kinetics of phosphorylation of Shc, previously demonstrated to be phosphorylated
      by Src downstream of c-Kit, was stronger and more rapid in the GNNK- form,
      whereas it showed slower kinetics in the GNNK+ form. Inhibition of Src family
      kinases with the specific Src family kinase inhibitor SU6656 altered the kinetics
      of activation of the GNNK- form of c-Kit so that it resembled that of the GNNK+
      form. In cells expressing the GNNK- form, SCF was rapidly degraded, whereas in
      cells expressing the GNNK+ form only showed a very slow rate of degradation of
      SCF. In the GNNK+ form the Src inhibitor SU6656 only had a weak effect on
      degradation, whereas in the GNNK- form it dramatically inhibited degradation. In
      summary, the two splice forms show, despite only a four-amino acid sequence
      difference, remarkable differences in their signaling capabilities.

PMID- 12511555
TI  - Interaction of the plasma membrane Ca2+ pump 4b/CI with the Ca2+/calmodulin
      dependent membrane-associated kinase CASK.
AB  - Spatial and temporal regulation of intracellular Ca(2+) is a key event in many
      signaling pathways. Plasma membrane Ca(2+)-ATPases (PMCAs) are major regulators
      of Ca(2+) homeostasis and bind to PDZ (PSD-95/Dlg/ZO-1) domains via their C
      termini. Various membrane-associated guanylate kinase family members have been
      identified as interaction partners of PMCAs. In particular, SAP90/PSD95,
      PSD93/chapsyn-110, SAP97, and SAP102 all bind to the C-terminal tails of PMCA "b"
      splice variants. Additionally, it has been demonstrated that PMCA4b interacts
      with neuronal nitric-oxide synthase and that isoform 2b interacts with Na(+)/H(+)
      exchanger regulatory factor 2, both via a PDZ domain. CASK (calcium/calmodulin
      dependent serine protein kinase) contains a calmodulin-dependent protein kinase
      like domain followed by PDZ, SH3, and guanylate kinase-like domains. In adult
      brain CASK is located at neuronal synapses and interacts with various proteins,
      e.g. neurexin and Veli/LIN-7. In kidney it is localized to renal epithelia.
      Surprisingly, interaction with the Tbr-1 transcription factor, nuclear transport,
      binding to DNA T-elements (in a complex with Tbr-1), and transcriptional
      competence has been shown. Here we show that the C terminus of PMCA4b binds to
      CASK and that both proteins co-precipitate from brain and kidney tissue lysates.
      Immunofluorescence staining revealed co-expression of PMCA, CASK, and calbindin-d
      28K in distal tubuli of rat kidney sections. To test if physical interaction of
      both proteins results in functional consequences we constructed a T-element
      dependent reporter vector and investigated luciferase activity in HEK293 lysates,
      previously co-transfected with PMCA4b expression and control vectors. Expression
      of wild-type PMCA resulted in an 80% decrease in T-element-dependent
      transcriptional activity, whereas co-expression of a point-mutated PMCA, with
      nearly eliminated Ca(2+) pumping activity, had only a small influence on
      regulation of transcriptional activity. These results provide evidence of a new
      direct Ca(2+)-dependent link from the plasma membrane to the nucleus.

PMID- 12511556
TI  - Cyclooxygenase-2 inhibits tumor necrosis factor alpha-mediated apoptosis in renal
      glomerular mesangial cells.
AB  - Renal mesangial cell apoptosis is a crucial repair mechanism in glomerular
      nephritis (GN). These cells express receptors to tumor necrosis factor alpha
      (TNFalpha), a cytokine with proapoptotic properties implicated in the resolution
      of GN. Progression to proliferative GN is accompanied by cyclooxygenase-mediated
      formation of prostaglandins and inefficient apoptosis of mesangial cells. The
      aims of this study were to quantify TNFalpha-mediated apoptosis in renal
      mesangial cells and to determine whether expression of the inducible form of
      cyclooxygenase, cylooxygenase-2 (COX-2), inhibits this apoptosis. By 24 h
      significant levels of apoptosis were induced by TNFalpha (100 ng/ml) or etoposide
      control (100 microm), as shown by phosphatidylserine externalization, caspase-3
      activation, development of a sub-G(0)/G(1) region, and distinct chromatin
      condensation. Using adenoviral-mediated delivery of the COX-2 gene (AdCOX-2)
      apoptotic features were prevented from appearing in AdCOX-2 cells treated with
      TNFalpha, whereas etoposide-treated AdCOX-2 cells were not protected.
      Furthermore, COX-2 expression, induced by the vasoconstrictor peptide ET-1 or the
      cytokine interleukin-1beta also inhibited TNFalpha-mediated but not etoposide
      mediated apoptosis, to an extent, similar to adenoviral COX-2 infection.
      Selective COX-2 inhibition by NS-398 restored TNFalpha-mediated apoptosis.
      Prostaglandin (PG) E(2) and PGI(2) were shown to be the major prostaglandin
      metabolites in AdCOX-2 cells. The addition of PGE(2) and PGI(2) protected against
      TNFalpha-mediated apoptosis. These results demonstrate COX-2 anti-apoptotic
      activity via a death receptor route and suggest that selective COX-2 inhibition
      may augment TNFalpha apoptosis in chronic inflammatory conditions.

PMID- 12511557
TI  - The tuberin-hamartin complex negatively regulates beta-catenin signaling
      activity.
AB  - Tuberous sclerosis complex (TSC) is characterized by the formation of hamartomas
      in multiple organs resulting from mutations in the TSC1 or TSC2 gene. Their
      protein products, hamartin and tuberin, respectively, form a functional complex
      that affects cell growth, differentiation, and proliferation. Several lines of
      evidence, including renal tumors derived from TSC2+/- animals, suggest that the
      loss or inhibition of tuberin is associated with up-regulation of cyclin D1. As
      cyclin D1 can be regulated through the canonical Wnt/beta-catenin signaling
      pathway, we hypothesize that the cell proliferative effects of hamartin and
      tuberin are partly mediated through beta-catenin. In this study, total beta
      catenin protein levels were found to be elevated in the TSC2-related renal
      tumors. Ectopic expression of hamartin and wild-type tuberin, but not mutant
      tuberin, reduced beta-catenin steady-state levels and its half-life. The TSC1
      TSC2 complex also inhibited Wnt-1 stimulated Tcf/LEF luciferase reporter
      activity. This inhibition was eliminated by constitutively active beta-catenin
      but not by Disheveled, suggesting that hamartin and tuberin function at the level
      of the beta-catenin degradation complex. Indeed, hamartin and tuberin co
      immunoprecipitated with glycogen synthase kinase 3 beta and Axin, components of
      this complex in a Wnt-1-dependent manner. Our data suggest that hamartin and
      tuberin negatively regulate beta-catenin stability and activity by participating
      in the beta-catenin degradation complex.

PMID- 12511558
TI  - A synergy control motif within the attenuator domain of CCAAT/enhancer-binding
      protein alpha inhibits transcriptional synergy through its PIASy-enhanced
      modification by SUMO-1 or SUMO-3.
AB  - One of the most common forms of functional interaction among transcription
      factors is the more than additive effect at promoters harboring multiple copies
      of a response element. The mechanisms that enable or control synergy at such
      compound response elements are poorly understood. We recently defined a common
      motif within the negative regulatory regions of multiple factors that operates by
      regulating their transcriptional synergy. We have identified such a synergy
      control (SC) motif embedded within the "attenuator domain" of CCAAT/enhancer
      binding protein alpha (C/EBPalpha), a key regulator of energy homeostasis and
      cellular differentiation. A Lys(159) --> Arg substitution within the SC motif
      does not alter C/EBPalpha activity from a single site but leads to enhanced
      transactivation from synthetic or natural compound response elements. The
      sequence of SC motifs overlaps with the recently defined consensus SUMO
      modification site, and we find that the SC motif is the major site of both SUMO-1
      and SUMO-3 modification in C/EBPalpha. Furthermore, the disruption of SC motif
      function is accompanied by loss of SUMO but not ubiquitin modification.
      C/EBPalpha interacts directly with the E2 SUMO-conjugating enzyme Ubc9 and can be
      SUMOylated in vitro using purified recombinant components. Notably, we find that
      PIASy has E3-like activity and enhances both SUMO-1 and SUMO-3 modification of
      C/EBPalpha in vivo and in vitro. Our results indicate that SUMO modification of
      SC motifs provides a means to rapidly control higher order interactions among
      transcription factors and suggests that SUMOylation may be a general mechanism to
      limit transcriptional synergy.

PMID- 12511559
TI  - High density lipoprotein-induced endothelial nitric-oxide synthase activation is
      mediated by Akt and MAP kinases.
AB  - High density lipoprotein (HDL) activates endothelial nitric-oxide synthase
      (eNOS), leading to increased production of the antiatherogenic molecule NO. A
      variety of stimuli regulate eNOS activity through signaling pathways involving
      Akt kinase and/or mitogen-activated protein (MAP) kinase. In the present study,
      we investigated the role of kinase cascades in HDL-induced eNOS stimulation in
      cultured endothelial cells and COS M6 cells transfected with eNOS and the HDL
      receptor, scavenger receptor B-I. HDL (10-50 microg/ml, 20 min) caused eNOS
      phosphorylation at Ser-1179, and dominant negative Akt inhibited both HDL
      mediated phosphorylation and activation of the enzyme. Phosphoinositide 3-kinase
      (PI3 kinase) inhibition or dominant negative PI3 kinase also blocked the
      phosphorylation and activation of eNOS by HDL. Studies with genistein and PP2
      showed that the nonreceptor tyrosine kinase, Src, is an upstream stimulator of
      the PI3 kinase-Akt pathway in this paradigm. In addition, HDL activated MAP
      kinase through PI3 kinase, and mitogen-activated protein kinase/extracellular
      signal-regulated kinase kinase inhibition fully attenuated eNOS stimulation by
      HDL without affecting Akt or eNOS Ser-1179 phosphorylation. Conversely, dominant
      negative Akt did not alter HDL-induced MAP kinase activation. These results
      indicate that HDL stimulates eNOS through common upstream, Src-mediated
      signaling, which leads to parallel activation of Akt and MAP kinases and their
      resultant independent modulation of the enzyme.

PMID- 12511560
TI  - Beta 1,4-galactosyltransferase (beta 4GalT)-IV is specific for GlcNAc 6-O
      sulfate. Beta 4GalT-IV acts on keratan sulfate-related glycans and a precursor
      glycan of 6-sulfosialyl-Lewis X.
AB  - The Galbeta1-->4(SO(3)(-)-->6)GlcNAc moiety is present in various N-linked and O
      linked glycans including keratan sulfate and 6-sulfosialyl-Lewis X, an L-selectin
      ligand. We previously found beta1,4-galactosyltransferase (beta4GalT) activity in
      human colonic mucosa, which prefers GlcNAc 6-O-sulfate (6SGN) as an acceptor to
      non-substituted GlcNAc (Seko, A., Hara-Kuge, S., Nagata, K., Yonezawa, S., and
      Yamashita, K. (1998) FEBS Lett. 440, 307-310). To identify the gene for this
      enzyme, we purified the enzyme from porcine colonic mucosa. The purified enzyme
      had the characteristic requirement of basic lipids for catalytic activity.
      Analysis of the partial amino acid sequence of the enzyme revealed that the
      purified beta4GalT has a similar sequence to human beta4GalT-IV. To confirm this
      result, we prepared cDNA for each of the seven beta4GalTs cloned to date and
      examined substrate specificities using the membrane fractions derived from
      beta4GalT-transfected COS-7 cells. When using several N-linked and O-linked
      glycans with or without 6SGN residues as acceptor substrates, only beta4GalT-IV
      efficiently recognized 6SGN, keratan sulfate-related oligosaccharides, and
      Galbeta1-->3(SO(3)(-)-->6GlcNAcbeta1-->6) GalNAcalpha1-O-pNP, a precursor for 6
      sulfosialyl-Lewis X. These results suggested that beta4GalT-IV is a 6SGN-specific
      beta4GalT and may be involved in the biosynthesis of various glycoproteins
      carrying a 6-O-sulfated N-acetyllactosamine moiety.

PMID- 12511561
TI  - The Set2 histone methyltransferase functions through the phosphorylated carboxyl
      terminal domain of RNA polymerase II.
AB  - The histone methyltransferase Set2, which specifically methylates lysine 36 of
      histone H3, has been shown to repress transcription upon tethering to a
      heterologous promoter. However, the mechanism of targeting and the consequence of
      Set2-dependent methylation have yet to be demonstrated. We sought to identify the
      protein components associated with Set2 to gain some insights into the in vivo
      function of this protein. Mass spectrometry analysis of the Set2 complex,
      purified using a tandem affinity method, revealed that RNA polymerase II (pol II)
      is associated with Set2. Immunoblotting and immunoprecipitation using antibodies
      against subunits of pol II confirmed that the phosphorylated form of pol II is
      indeed an integral part of the Set2 complex. Gst-Set2 preferentially binds to CTD
      synthetic peptides phosphorylated at serine 2, and to a lesser extent, serine 5
      phosphorylated peptides, but has no affinity for unphosphorylated CTD, suggesting
      that Set2 associates with the elongating form of the pol II. Furthermore, we show
      that set2Delta ppr2Delta double mutants (PPR2 encodes TFIIS, a transcription
      elongation factor) are synthetically hypersensitive to 6-azauracil, and that
      deletions in the CTD reduce in vivo levels of H3 lysine 36 methylation.
      Collectively, these results suggest that Set2 is involved in regulating
      transcription elongation through its direct contact with pol II.

PMID- 12511562
TI  - Bidirectional silencing and DNA methylation-sensitive methylation-spreading
      properties of the Kcnq1 imprinting control region map to the same regions.
AB  - The mechanisms underlying the phenomenon of genomic imprinting are poorly
      understood. Accumulating evidence suggests that imprinting control regions (ICR)
      associated with the imprinted genes play an important role in creation of
      imprinted expression domains by propagating parent-of-origin-specific epigenetic
      modifications. We have recently documented that the Kcnq1 ICR unidirectionally
      blocks enhancer-promoter communications in a methylation-dependent manner in Hep
      3B and Jurkat cell lines. In this report we show that the Kcnq1 ICR harbors
      bidirectional silencing and methylation-sensitive methylation-spreading
      properties in a lineage-specific manner. We fine map both of these functions to
      two critical regions, and loss of one these regions results in loss of silencing
      as well as methylation spreading. The cell type-specific functions of the Kcnq1
      ICR suggest binding of cell type-specific factors to various cis elements within
      the ICR. Fine mapping of the silencing and methylation-spreading functions to the
      same regions explains the fact that the silencing factors associated with this
      region primarily repress the neighboring genes and that methylation occurs as a
      consequence of silencing.

PMID- 12511563
TI  - A novel fluorescent toxin to detect and investigate Kv1.3 channel up-regulation
      in chronically activated T lymphocytes.
AB  - T lymphocytes with unusually high expression of the voltage-gated Kv1.3 channel
      (Kv1.3(high) cells) have been implicated in the pathogenesis of experimental
      autoimmune encephalomyelitis, an animal model for multiple sclerosis. We have
      developed a fluoresceinated analog of ShK (ShK-F6CA), the most potent known
      inhibitor of Kv1.3, for detection of Kv1.3(high) cells by flow cytometry. ShK
      F6CA blocked Kv1.3 at picomolar concentrations with a Hill coefficient of 1 and
      exhibited >80-fold specificity for Kv1.3 over Kv1.1 and other K(V) channels. In
      flow cytometry experiments, ShK-F6CA specifically stained Kv1.3-expressing cells
      with a detection limit of approximately 600 channels per cell. Rat and human T
      cells that had been repeatedly stimulated 7-10 times with antigen were readily
      distinguished on the basis of their high levels of Kv1.3 channels (>600
      channels/cell) and ShK-F6CA staining from resting T cells or cells that had
      undergone 1-3 rounds of activation. Functional Kv1.3 expression levels increased
      substantially in a myelin-specific rat T cell line following myelin antigen
      stimulation, peaking at 15-20 h and then declining to baseline over the next 7
      days, in parallel with the acquisition and loss of encephalitogenicity. Both
      calcium- and protein kinase C-dependent pathways were required for the antigen
      induced Kv1.3 up-regulation. ShK-F6CA might be useful for rapid and quantitative
      detection of Kv1.3(high) expressing cells in normal and diseased tissues, and to
      visualize the distribution of functional channels in intact cells.

PMID- 12511564
TI  - Ca2+-induced conformational transition in the inhibitory and regulatory regions
      of cardiac troponin I.
AB  - Cardiac muscle activation is initiated by the binding of Ca(2+) to the single N
      domain regulatory site of cardiac muscle troponin C (cTnC). Ca(2+) binding causes
      structural changes between cTnC and two critical regions of cardiac muscle
      troponin I (cTnI): the regulatory region (cTnI-R, residues 150-165) and the
      inhibitory region (cTnI-I, residues130-149). These changes are associated with a
      decreased cTnI affinity for actin and a heightened affinity for cTnC. Using
      Forster resonance energy transfer, we have measured three intra-cTnI distances in
      the deactivated (Mg(2+)-saturated) and Ca(2+)-activated (Ca(2+)-saturated) states
      in reconstituted binary (cTnC-cTnI) and ternary (cTnC-cTnI-cTnT) troponin
      complexes. Distance A (spanning cTnI-R) was unaltered by Ca(2+). Distances B
      (spanning both cTnI-R and cTnI-I) and C (from a residue flanking cTnI-I to a
      residue in the center of cTnI-R) exhibited Ca(2+)-induced increases of >8 A.
      These results compliment our previous determination of the distance between
      residues flanking cTnI-I alone. Together, the data suggest that Ca(2+) activation
      causes residues within cTnI-I to switch from a beta-turn/coil to an extended
      quasi-alpha-helical conformation as the actin-contacts are broken, whereas cTnI-R
      remains alpha-helical in both Mg(2+)- and Ca(2+)-saturated states. We have used
      the data to construct a structural model of the cTnI inhibitory and regulatory
      regions in the Mg(2+)- and Ca(2+)-saturated states.

PMID- 12511565
TI  - The NFY transcription factor inhibits von Willebrand factor promoter activation
      in non-endothelial cells through recruitment of histone deacetylases.
AB  - Human von Willebrand factor (VWF) gene sequences +155 to +247 contain cis-acting
      elements that contribute toward endothelial specific activation of the VWF
      promoter. Analyses of this region demonstrated the presence of a GATA-binding
      site that is necessary for the promoter activation in endothelial cells. We have
      reported recently the presence of a novel NFY-binding sequence in this region
      that does not conform to the consensus NFY-binding sequence CCAAT. NFY was shown
      to function as a repressor of the VWF promoter through interaction with this
      novel binding site. Here we report that the NFY interacts with histone
      deacetylases (HDACs) in a cell type-specific manner and recruits them to the VWF
      promoter to inhibit the promoter activity in non-endothelial cells. Analyses of
      the acetylation status of histones in the chromatin region containing the VWF
      promoter sequences demonstrated that these sequences are associated with
      acetylated histone H4 specifically in endothelial cells. It was also demonstrated
      that HDACs are specifically recruited to the same chromatin region in non
      endothelial cells. We also demonstrated that GATA6 is the GATA family member that
      interacts with the VWF promoter and that GATA6 is associated with NFY
      specifically in non-endothelial cells. We propose that NFY recruits HDACs to the
      VWF promoter, which may result in deacetylation of GATA6 as well as of histones
      in non-endothelial cells, thus leading to promoter inactivation. In endothelial
      cells, however, association of HDACs, NFY, and GATA6 is interrupted potentially
      through endothelial cell-specific signaling/mechanism, thus favoring the balance
      toward acetylation and activation of the VWF promoter.

PMID- 12511566
TI  - Staphylococcus aureus gyrase-quinolone-DNA ternary complexes fail to arrest
      replication fork progression in vitro. Effects of salt on the DNA binding mode
      and the catalytic activity of S. aureus gyrase.
AB  - Type II topoisomerases bind to DNA at the catalytic domain across the DNA gate.
      DNA gyrases also bind to DNA at the non-homologous C-terminal domain of the GyrA
      subunit, which causes the wrapping of DNA about itself. This unique mode of DNA
      binding allows gyrases to introduce the negative supercoils into DNA molecules.
      We have investigated the biochemical characteristics of Staphylococcus aureus (S.
      aureus) gyrase. S. aureus gyrase is known to require high concentrations of
      potassium glutamate (K-Glu) for its supercoiling activity. However, high
      concentrations of K-Glu are not required for its relaxation and decatenation
      activities. This is due to the requirement of high concentrations of K-Glu for S.
      aureus gyrase-mediated wrapping of DNA. These results suggest that S. aureus
      gyrase can bind to DNA at the catalytic domain independent of K-Glu
      concentration, but high concentrations of K-Glu are required for the binding of
      the C-terminal domain of GyrA to DNA and the wrapping of DNA. Thus, salt
      modulates the DNA binding mode and the catalytic activity of S. aureus gyrase.
      Quinolone drugs can stimulate the formation of covalent S. aureus gyrase-DNA
      complexes, but high concentrations of K-Glu inhibit the formation of S. aureus
      gyrase-quinolone-DNA ternary complexes. In the absence of K-Glu, ternary
      complexes formed with S. aureus gyrase cannot arrest replication fork progression
      in vitro, demonstrating that the formation of a wrapped ternary complex is
      required for replication fork arrest by a S. aureus gyrase-quinolone-DNA ternary
      complex.

PMID- 12511567
TI  - A novel ubiquitin fusion system bypasses the mitochondria and generates
      biologically active Smac/DIABLO.
AB  - Smac/DIABLO is a mitochondrial protein that is proteolytically processed and
      released during apoptosis along with cytochrome c and other proapoptotic factors.
      Once in the cytosol, Smac protein binds to inhibitors of apoptosis (IAP) proteins
      and disrupts the ability of the IAPs to inhibit caspases 3, 7, and 9. The
      requirement for mitochondrial processing and release has complicated efforts to
      delineate the effect of Smac overexpression and IAP inhibition on cell death
      processes. In this report, we document a novel expression system using ubiquitin
      fusions to express mature, biologically active Smac in the cytosol of transfected
      cells. Processing of the ubiquitin-Smac fusions is rapid and complete and
      generates mature Smac protein initiating correctly with the Ala-Val-Pro-Ile
      tetrapeptide sequence that is required for proper function. The biological
      activity of this exogenous protein was demonstrated by its interaction with X
      linked IAP, one of the most potent of the IAPs. The presence of mature Smac was
      not sufficient to trigger apoptosis of healthy cells. However, cells with excess
      Smac protein were greatly sensitized to apoptotic triggers such as etoposide
      exposure. Cancer cells typically display deregulated apoptotic pathways,
      including Bcl2 overexpression, thereby suppressing the release of cytochrome c
      and Smac. The ability to circumvent the requirement for mitochondrial processing
      and release is critical to developing Smac as a possible gene therapy payload in
      cancer chemosensitization.

PMID- 12511568
TI  - Ceramide increases oxidative damage due to inhibition of catalase by caspase-3
      dependent proteolysis in HL-60 cell apoptosis.
AB  - We investigated through which mechanisms ceramide increased oxidative damage to
      induce leukemia HL-60 cell apoptosis. When 5 microm N-acetylsphingosine (C(2)
      ceramide) or 20 microm H(2)O(2) alone induced little increase of reactive oxygen
      species (ROS) generation as judged by the 2'-7'-dichlorofluorescin diacetate
      method, 20 microm H(2)O(2) enhanced oxidative damage as judged by ROS
      accumulation, and thiobarbituric acid-reactive substance production after
      pretreatment with 5 microm C(2)-ceramide at least for 12 h. The treatment with a
      catalase inhibitor, 3-amino-1h-1,2,4-triazole, increased oxidative damage and
      apoptosis induced by H(2)O(2), and in contrast, purified catalase inhibited the
      enhancement of oxidative damage by H(2)O(2) in ceramide-pretreated cells,
      suggesting that the oxidative effect of ceramide is involved in catalase
      regulation. Indeed, C(2)-ceramide inhibited the activity of immunoprecipitated
      catalase and decreased the levels of catalase protein in a time-dependent manner.
      Moreover, acetyl-Asp-Met-Gln-Asp-aldehyde, which dominantly inhibited caspase-3
      and blocked the increase of oxidative damage and apoptosis due to C(2)-ceramide
      induced catalase depletion at protein and activity levels. In vitro, active and
      purified caspase-3, but not caspase-6, -8, and -9, inhibited catalase activity
      and induced the proteolysis of catalase protein whereas these in vitro effects of
      caspase-3 were blocked by acetyl-Asp-Met-Gln-Asp-aldehyde. Taken together, it is
      suggested that H(2)O(2) enhances apoptosis in ceramide-pretreated cells, because
      ceramide increases oxidative damage by inhibition of ROS scavenging ability
      through caspase-3-dependent proteolysis of catalase.

PMID- 12511569
TI  - E-cadherin negatively regulates CD44-hyaluronan interaction and CD44-mediated
      tumor invasion and branching morphogenesis.
AB  - CD44 is a principal cell-surface receptor for hyaluronan (HA). Up-regulation of
      CD44 is often associated with morphogenesis and tumor invasion. On the contrary,
      reduction of cell-cell adhesion due to down-regulation of E-cadherin is
      associated with the invasive and metastatic phenotype of carcinomas. In our
      current study, we investigated the functional relationship between CD44 and E
      cadherin. We established an inverse correlation between CD44 and E-cadherin
      indicating that the cells expressing higher levels of E-cadherin display weaker
      binding affinity between CD44 and HA. By using TA3 murine mammary carcinoma (TA3)
      cells, which display CD44-dependent HA binding, branching morphogenesis, and
      invasion, we demonstrated an inverse functional relationship between CD44 and E
      cadherin by transfecting exogenous E-cadherin into the cells. Our results showed
      that increased expression of E-cadherin in TA3 cells, but not ICAM-1, weakens the
      binding between CD44 and HA and blocks spreading of the cells on HA substratum
      and CD44-mediated branching morphogenesis and tumor cell invasion. The results
      reported here demonstrated for the first time that E-cadherin negatively
      regulated CD44-HA interaction and CD44 function and suggested that balanced
      function of CD44 and E-cadherin may be essential for normal epithelial cell
      functions, and imbalanced up-regulation of CD44 function and/or down-regulation
      of E-cadherin function likely contributes to tumor progression.

PMID- 12511570
TI  - Identification and characterization of three Drosophila melanogaster
      glucuronyltransferases responsible for the synthesis of the conserved
      glycosaminoglycan-protein linkage region of proteoglycans. Two novel homologs
      exhibit broad specificity toward oligosaccharides from proteoglycans,
      glycoproteins, and glycosphingolipids.
AB  - The Drosophila melanogaster genome contains three putative glucuronyltransferases
      homologous to human GlcAT-I and GlcAT-P. These enzymes are predicted to be
      beta1,3-glucuronyltransferases involved in the synthesis of the glycosaminoglycan
      (GAG)-protein linkage region of proteoglycans and the HNK-1 carbohydrate epitope
      of glycoproteins, respectively. The genes encode active enzymes, which we have
      designated DmGlcAT-I, DmGlcAT-BSI, and DmGlcAT-BSII (where BS stands for "broad
      specificity"). Protein A-tagged truncated soluble forms of all three enzymes
      efficiently transfer GlcUA from UDP-GlcUA to the linkage region trisaccharide
      Galbeta1-3Galbeta1-4Xyl. Strikingly, DmGlcAT-I has specificity for Galbeta1
      3Galbeta1-4Xyl, whereas DmGlcAT-BSI and DmGlcAT-BSII act on a wide array of
      substrates with non-reducing terminal beta1,3- and beta1,4-linked Gal residues.
      Their highest activities are obtained with asialoorosomucoid with a terminal
      Galbeta1-4GlcNAc sequence, indicating their possible involvement in the synthesis
      of the HNK-1 epitope in addition to the GAG-protein linkage region. Galbeta1
      3GlcNAc and Galbeta1-3GalNAc, disaccharide structures widely found in N- and O
      glycans of glycoproteins and glycolipids, also serve as acceptors for DmGlcAT-BSI
      and -BSII. Transcripts of all three enzymes are ubiquitously expressed throughout
      the developmental stages and in adult tissues of Drosophila. Thus, all three
      glucuronyltransferases are likely involved in the synthesis of the GAG-protein
      linkage region in Drosophila, and DmGlcAT-BSI and -BSII appear to be involved in
      various GlcUA transfer reactions for the synthesis of proteoglycans,
      glycoproteins, and glycolipids. This activity distinguishes these
      glucuronyltransferases from their mammalian homologs GlcAT-P and GlcAT-D (or -S).
      Sequence alignment of the Drosophila glucuronyltransferases with homologs in
      human, rat, and Caenorhabditis elegans demonstrates the conservation of a
      majority of the critical amino acid residues in the active sites of the three
      Drosophila enzymes.

PMID- 12511571
TI  - Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in
      human cells.
AB  - Heme oxygenase 1 (HO-1) catalyzes heme breakdown, eventually releasing iron,
      carbon monoxide, and bilirubin IXalpha. HO-1 is induced by its substrate heme and
      various environmental factors, which represents a protective response against
      oxidative stresses. Here we show that hypoxia represses HO-1 expression in three
      human cell types but induces it in rat, bovine, and monkey cells, indicating the
      inter-species difference in the hypoxic regulation of HO-1 expression. The
      hypoxia-mediated repression of HO-1 expression is consistently associated with
      the induction of Bach1, a heme-regulated transcriptional repressor, in human
      cells. Bach1 is a basic leucine zipper protein, forming a heterodimer with a
      small Maf protein. Expression of HO-1 was also reduced in human cells when
      exposed to interferon-gamma or an iron chelator desferrioxamine, each of which
      induced Bach1 expression. In contrast, induction of HO-1 expression by CoCl(2) is
      associated with reduced expression of Bach1 mRNA. Thus, expression of HO-1 and
      Bach1 is inversely regulated. We have identified a Maf recognition element in the
      human HO-1 gene that is required for repression of a reporter gene by hypoxia and
      targeted by Bach1. Therefore, Bach1 functions as a hypoxia-inducible repressor
      for the HO-1 gene, thereby contributing to fine-tuning of oxygen homeostasis in
      human cells.

PMID- 12511572
TI  - Co-overexpression of Escherichia coli RNA polymerase subunits allows isolation
      and analysis of mutant enzymes lacking lineage-specific sequence insertions.
AB  - The study of mutant enzymes can reveal important details about the fundamental
      mechanism and regulation of RNA polymerase, the central enzyme of gene
      expression. However, such studies are complicated by the multisubunit structure
      of RNA polymerase and by its indispensability for cell growth. Previously, mutant
      RNA polymerases have been produced by in vitro assembly from isolated subunits or
      by in vivo assembly upon overexpression of a single mutant subunit. Both
      approaches can fail if the mutant subunit is toxic or incorrectly folded. Here we
      describe an alternative strategy, co-overexpression and in vivo assembly of RNA
      polymerase subunits, and apply this method to characterize the role of sequence
      insertions present in the Escherichia coli enzyme. We find that co-overexpression
      of its subunits allows assembly of an RNA polymerase lacking a 188-amino acid
      insertion in the beta' subunit. Based on experiments with this and other mutant
      E. coli enzymes with precisely excised sequence insertions, we report that the
      beta' sequence insertion and, to a lesser extent, an N-terminal beta sequence
      insertion confer characteristic stability to the open initiation complex,
      frequency of abortive initiation, and pausing during transcript elongation
      relative to RNA polymerases, such as that from Bacillus subtilis, that lack the
      sequence insertions.

PMID- 12511573
TI  - Skp1 and the F-box protein Pof6 are essential for cell separation in fission
      yeast.
AB  - Here we report functional characterization of the essential fission yeast Skp1
      homologue. We have created a conditional allele of skp1 (skp1-3f) mimicking the
      mutation in the budding yeast skp1-3 allele. Although budding yeast skp1-3
      arrests at the G(1)/S transition, skp1-3f cells progress through S phase and
      instead display two distinct phenotypes. A fraction of the skp1-3f cells arrest
      in mitosis with high Cdc2 activity. Other skp1-3f cells as well as the skp1
      deleted cells accumulate abnormal thick septa leading to defects in cell
      separation. Subsequent identification of 16 fission yeast F-box proteins led to
      identification of the product of pof6 (for pombe F-box) as a Skp1-associated
      protein. Interestingly, cells deleted for the essential pof6 gene display a
      similar cell separation defect noted in skp1 mutants, and Pof6 localizes to septa
      and cell tips. Purification of Pof6 demonstrates association of Skp1, whereas the
      Pcu1 cullin was absent from the complex. These findings reveal an essential non
      Skp1-Cdc53/Cullin-F-box protein function for the fission yeast Skp1 homologue and
      the F-box protein Pof6 in cell separation.

PMID- 12511574
TI  - Histone acetylation and activation of cAMP-response element-binding protein
      regulate transcriptional activation of MKP-M in lipopolysaccharide-stimulated
      macrophages.
AB  - MKP-M is a dual specificity phosphatase that preferentially inactivates JNK. mkp
      M gene expression is rapidly induced by lipopolysaccharide (LPS) stimulation in
      macrophages and is involved in the negative regulation of LPS-mediated JNK
      activation and tumor necrosis factor-alpha secretion. To reveal the
      transcriptional regulation of the mkp-M gene, we isolated the mouse mkp-M gene
      and mapped its transcriptional start site. Luciferase reporter plasmids
      containing 5'-upstream regions of the mkp-M gene were stably transfected into
      RAW264.7 cells. The assays using these cells revealed that the promoter region
      between -252 and -135 is required for mkp-M promoter activation. Sequencing
      analysis revealed E box and CREB-responsive elements in this region, and
      electromobility shift assays and mutagenesis confirmed that both of these
      elements are essential for LPS responsiveness of the mkp-M gene. We also utilized
      chromatin immunoprecipitation assay and found that LPS stimulation caused
      acetylation of histone H3 and H4 at mkp-M promoter in RAW264.7 cells. Consistent
      with this, a histone deacetylase inhibitor, trichostatin A, increased endogenous
      mkp-M gene transcription. Finally, DNase I hypersensitivity site mapping revealed
      the inducible hypersensitivity site after LPS stimulation around the location of
      the E box and CREB-responsive elements. Altogether, our data indicated that the
      activation of mkp-M gene transcription in macrophages by LPS is associated with
      histone acetylation and chromatin remodeling.

PMID- 12511575
TI  - Crystal structure of ATP phosphoribosyltransferase from Mycobacterium
      tuberculosis.
AB  - The N-1-(5'-phosphoribosyl)-ATP transferase catalyzes the first step of the
      histidine biosynthetic pathway and is regulated by a feedback mechanism by the
      product histidine. The crystal structures of the N-1-(5'-phosphoribosyl)-ATP
      transferase from Mycobacterium tuberculosis in complex with inhibitor histidine
      and AMP has been determined to 1.8 A resolution and without ligands to 2.7 A
      resolution. The active enzyme exists primarily as a dimer, and the histidine
      inhibited form is a hexamer. The structure represents a new fold for a
      phosphoribosyltransferase, consisting of three continuous domains. The inhibitor
      AMP binds in the active site cavity formed between the two catalytic domains. A
      model for the mechanism of allosteric inhibition has been derived from
      conformational differences between the AMP:His-bound and apo structures.

PMID- 12511576
TI  - Interactions between Na,K-ATPase alpha-subunit ATP-binding domains.
AB  - The reaction mechanism of the Na,K-ATPase is thought to involve a number of
      ligand-induced conformational changes. The specific amino acid residues
      responsible for binding many of the important ligands have been identified;
      however, details of the specific conformational changes produced by ligand
      binding are largely undescribed. The experiments described in this paper begin to
      identify interactions between domains of the Na,K-ATPase alpha-subunit that
      depend on the presence of particular ligands. The major cytoplasmic loop (between
      TM4 and TM5), which we have previously shown contains the ATP-binding domain, was
      overexpressed in bacteria either with a His(6) tag or as a fusion protein with
      glutathione S-transferase. We have observed that these polypeptides associate in
      the presence of MgATP. Incubation with [gamma-(32)P]ATP under conditions that
      result in phosphorylation of the full-length Na,K-ATPase did not result in (32)P
      incorporation into either the His(6) tag or glutathione S-transferase fusion
      proteins. The MgATP-induced association was strongly inhibited by prior
      modification of the fusion proteins with fluorescein isothiocyanate or by
      simultaneous incubation with 10 microm eosin, indicating that the effect of MgATP
      is due to interactions within the nucleotide-binding domain. These data are
      consistent with Na,K-ATPase associating within cells via interactions in the
      nucleotide-binding domains. Although any functional significance of these
      associations for ion transport remains unresolved, they may play a role in cell
      function and in modulating interactions between the Na,K-ATPase and other
      proteins.

PMID- 12511577
TI  - Activity-stability relationships in extremophilic enzymes.
AB  - Psychrophilic, mesophilic, and thermophilic alpha-amylases have been studied as
      regards their conformational stability, heat inactivation, irreversible
      unfolding, activation parameters of the reaction, properties of the enzyme in
      complex with a transition state analog, and structural permeability. These data
      allowed us to propose an energy landscape for a family of extremophilic enzymes
      based on the folding funnel model, integrating the main differences in
      conformational energy, cooperativity of protein unfolding, and temperature
      dependence of the activity. In particular, the shape of the funnel bottom, which
      depicts the stability of the native state ensemble, also accounts for the
      thermodynamic parameters of activation that characterize these extremophilic
      enzymes, therefore providing a rational basis for stability-activity
      relationships in protein adaptation to extreme temperatures.

PMID- 12511578
TI  - Identification of Uhp1, a ubiquitinated histone-like protein, as a
      target/mediator of Rhp6 in mating-type silencing in fission yeast.
AB  - Mating-type silencing in Schizosaccharomyces pombe is brought about by
      cooperative interactions between cis-acting DNA sequences flanking mat2P and
      mat3M and the trans-acting factors, namely Swi6, Clr1-Clr4, Clr6, and Rik1. In
      addition, DNA repair gene rhp6, which plays a role in post-replication DNA repair
      and ubiquitination of proteins including histones, is also involved in silencing,
      albeit in a unique way; its effect on silencing and chromatin structure of the
      donor loci is dependent on their switching competence. Earlier, we hypothesized
      the existence of a mediator of Rhp6 that plays a role in reestablishment of the
      chromatin structure coincidentally with DNA replication associated with mating
      type switching. Here we report the identification of a 22-kDa protein as an in
      vivo target and mediator of Rhp6 in mating-type silencing. The level of this
      protein is greatly elevated in sng1-1/rhp6(-) mutant and rhp6Delta as compared
      with wild type strain. Both the deletion and overexpression of the gene encoding
      this protein elicit switching-dependent loss of silencing. Furthermore, the 22
      kDa protein undergoes Rhp6-dependent multiubiquitination and associates with mat2
      locus during S phase in wild type cells. Interestingly, it contains a histone
      fold motif similar to that of histone H2A, and like histone H2A, it interacts
      strongly with histone H2B in vitro. These results indicate that the 22-kDa
      protein, renamed as the ubiquitinated histone-like protein Uhp1, is an in vivo
      target/mediator of Rhp6 in silencing. Thus, regulation of association of Uhp1
      with chromatin and ubiquitination followed by degradation may play a role in
      reestablishment of inactive chromatin structure at the silent mating-type loci.

PMID- 12511579
TI  - Neurodegeneration: what is it and where are we?

PMID- 12511580
TI  - Alzheimer disease therapy: can the amyloid cascade be halted?

PMID- 12511581
TI  - New weapons against inflammation: dual inhibitors of phospholipase A2 and
      transglutaminase.

PMID- 12511582
TI  - Disabling multiple integrins from the inside out.

PMID- 12511583
TI  - PARticipation in inflammation.

PMID- 12511584
TI  - Machinations of the marrow.

PMID- 12511585
TI  - Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor
      expression in the pathogenesis of lung cancer.

PMID- 12511586
TI  - Essential role for proteinase-activated receptor-2 in arthritis.
AB  - Using physiological, pharmacological, and gene disruption approaches, we
      demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in
      mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic
      inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice,
      being reduced by more than fourfold compared with wild-type mice, with virtually
      no histological evidence of joint damage. Mice heterozygous for PAR-2 gene
      disruption showed an intermediate phenotype. PAR-2 expression, normally limited
      to endothelial cells in small arterioles, was substantially upregulated 2 weeks
      after induction of inflammation, both in synovium and in other periarticular
      tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular
      injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint
      swelling and synovial hyperemia. Given the absence of the chronic inflammatory
      response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR
      2 in mediating chronic inflammation, thereby identifying a novel and important
      therapeutic target for the management of chronic inflammatory diseases such as
      rheumatoid arthritis.

PMID- 12511587
TI  - Inhibition of skin tumor growth and angiogenesis in vivo by activation of
      cannabinoid receptors.
AB  - Nonmelanoma skin cancer is one of the most common malignancies in humans.
      Different therapeutic strategies for the treatment of these tumors are currently
      being investigated. Given the growth-inhibiting effects of cannabinoids on
      gliomas and the wide tissue distribution of the two subtypes of cannabinoid
      receptors (CB(1) and CB(2)), we studied the potential utility of these compounds
      in anti-skin tumor therapy. Here we show that the CB(1) and the CB(2) receptor
      are expressed in normal skin and skin tumors of mice and humans. In cell culture
      experiments pharmacological activation of cannabinoid receptors induced the
      apoptotic death of tumorigenic epidermal cells, whereas the viability of
      nontransformed epidermal cells remained unaffected. Local administration of the
      mixed CB(1)/CB(2) agonist WIN-55,212-2 or the selective CB(2) agonist JWH-133
      induced a considerable growth inhibition of malignant tumors generated by
      inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors
      showed an increased number of apoptotic cells. This was accompanied by impairment
      of tumor vascularization, as determined by altered blood vessel morphology and
      decreased expression of proangiogenic factors (VEGF, placental growth factor, and
      angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid
      treated tumors. These results support a new therapeutic approach for the
      treatment of skin tumors.

PMID- 12511588
TI  - A novel form of integrin dysfunction involving beta1, beta2, and beta3 integrins.
AB  - The adhesion receptors known as integrins perform key functions for hematopoietic
      cells. The platelet integrin alphaIIbbeta3 is critical in hemostasis, and the
      beta1 and beta2 integrins on leukocytes have many roles in cell-mediated
      immunity. Mutations in the beta2 subunit lead to integrin nonexpression and to an
      immune deficiency, leukocyte adhesion deficiency-1. Mutations in either the alpha
      or beta subunit of alphaIIbbeta3 usually lead to integrin nonexpression and a
      bleeding tendency termed Glanzmann thrombasthenia. Here we describe a unique
      patient with clinical features of both Glanzmann thrombasthenia and leukocyte
      adhesion deficiency-1. The patient has normal expression of beta1, beta2, and
      beta3 integrins, but all are dysfunctional. The key findings are that "inside
      out" signaling pathways leading to integrin activation are defective and that
      this is associated with abnormal integrin clustering. The integrins themselves
      are intact and capable of function following extracellular stimulation. T cell
      motility is normal, as are the expression levels and electrophoretic
      characteristics of all cytoskeletal and signaling proteins tested, except PKC
      alpha, which has enhanced expression in the patient's cells. To our knowledge,
      this is the first description of a dysfunction affecting three classes of
      integrins. We propose that it is caused by a lesion in an intracellular factor or
      signaling pathway essential for integrin activation in hematopoietic cells and
      results in lack of regulation of clustering, an essential component of integrin
      mediated adhesion.

PMID- 12511589
TI  - A novel streptococcal surface protease promotes virulence, resistance to
      opsonophagocytosis, and cleavage of human fibrinogen.
AB  - Group B streptococcus (GBS) is an important human pathogen. In this study, we
      sought to identify mechanisms that may protect GBS from host defenses in addition
      to its capsular polysaccharide. A gene encoding a cell-surface-associated protein
      (cspA) was characterized from a highly virulent type III GBS isolate, COH1. Its
      sequence indicated that it is a subtilisin-like extracellular serine protease
      homologous to streptococcal C5a peptidases and caseinases of lactic acid
      bacteria. The wild-type strain cleaved the alpha chain of human fibrinogen,
      whereas a cspA mutant, TOH121, was unable to cleave fibrinogen. We observed
      aggregated material when COH1 was incubated with fibrinogen but not when the
      mutant strain was treated similarly. This suggested that the product(s) of
      fibrinogen cleavage have strong adhesive properties and may be similar to fibrin.
      The cspA gene was present among representative clinical isolates from all nine
      capsular serotypes, as revealed by Southern blotting. A cspA(-) mutant was ten
      times less virulent in a neonatal rat sepsis model of GBS infections, as measured
      by LD(50) analysis. In addition, the cspA(-) mutant was significantly more
      sensitive than the wild-type strain to opsonophagocytic killing by human
      neutrophils in vitro. Taken together, the results suggest that cleavage of
      fibrinogen by CspA may increase the lethality of GBS infection, potentially by
      protecting the bacterium from opsonophagocytic killing.

PMID- 12511590
TI  - Distinct progenitor populations in skeletal muscle are bone marrow derived and
      exhibit different cell fates during vascular regeneration.
AB  - Vascular progenitors were previously isolated from blood and bone marrow; herein,
      we define the presence, phenotype, potential, and origin of vascular progenitors
      resident within adult skeletal muscle. Two distinct populations of cells were
      simultaneously isolated from hindlimb muscle: the side population (SP) of highly
      purified hematopoietic stem cells and non-SP cells, which do not reconstitute
      blood. Muscle SP cells were found to be derived from, and replenished by, bone
      marrow SP cells; however, within the muscle environment, they were phenotypically
      distinct from marrow SP cells. Non-SP cells were also derived from marrow stem
      cells and contained progenitors with a mesenchymal phenotype. Muscle SP and non
      SP cells were isolated from Rosa26 mice and directly injected into injured muscle
      of genetically matched recipients. SP cells engrafted into endothelium during
      vascular regeneration, and non-SP cells engrafted into smooth muscle. Thus,
      distinct populations of vascular progenitors are resident within skeletal muscle,
      are derived from bone marrow, and exhibit different cell fates during injury
      induced vascular regeneration.

PMID- 12511591
TI  - Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype
      of normal human airway epithelial cells.
AB  - Tobacco-related diseases such as lung cancer cause over 4.2 million deaths
      annually, with approximately 400,000 deaths per year occurring in the US.
      Genotoxic effects of tobacco components have been described, but effects on
      signaling pathways in normal cells have not been described. Here, we show
      activation of the serine/threonine kinase Akt in nonimmortalized human airway
      epithelial cells in vitro by two components of cigarette smoke, nicotine and the
      tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
      Activation of Akt by nicotine or NNK occurred within minutes at concentrations
      achievable by smokers and depended upon alpha(3)-/alpha(4)-containing or alpha(7)
      containing nicotinic acetylcholine receptors, respectively. Activated Akt
      increased phosphorylation of downstream substrates such as GSK-3, p70(S6K), 4EBP
      1, and FKHR. Treatment with nicotine or NNK attenuated apoptosis caused by
      etoposide, ultraviolet irradiation, or hydrogen peroxide and partially induced a
      transformed phenotype manifest as loss of contact inhibition and loss of
      dependence on exogenous growth factors or adherence to ECM. In vivo, active Akt
      was detected in airway epithelial cells and lung tumors from NNK-treated A/J
      mice, and in human lung cancers derived from smokers. Redundant Akt activation by
      nicotine and NNK could contribute to tobacco-related carcinogenesis by regulating
      two processes critical for tumorigenesis, cell growth and apoptosis.

PMID- 12511592
TI  - The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body
      insulin sensitivity.
AB  - AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and
      lipid metabolism. To better understand the physiological role of AMPK, we
      generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene
      was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed
      period and during an oral glucose challenge associated with low insulin plasma
      levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L
      arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice
      have reduced insulin-stimulated whole-body glucose utilization and muscle
      glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic
      clamp technique. Surprisingly, both parameters were not altered in mice
      expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore,
      glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These
      data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates
      insulin action. Concordantly, we found an increased daily urinary catecholamine
      excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic
      nervous system that could explain both the impaired insulin secretion and insulin
      sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic
      subunit is important for whole-body insulin action in vivo, probably through
      modulation of sympathetic nervous activity.

PMID- 12511593
TI  - A PEST sequence in ABCA1 regulates degradation by calpain protease and
      stabilization of ABCA1 by apoA-I.
AB  - Cholesterol-loaded macrophage foam cells are a central component of
      atherosclerotic lesions. ABCA1, the defective molecule in Tangier disease,
      mediates the efflux of phospholipids and cholesterol from cells to apoA-I,
      reversing foam cell formation. In ABCA1, we identified a sequence rich in
      proline, glutamic acid, serine, and threonine (PEST sequence) that enhances the
      degradation of ABCA1 by calpain protease and thereby controls the cell surface
      concentration and cholesterol efflux activity of ABCA1. In an apparent positive
      feedback loop, apoA-I binds ABCA1, promotes lipid efflux, inhibits calpain
      degradation, and leads to increased levels of ABCA1. ApoA-I infusion also
      increases ABCA1 in vivo. These studies reveal a novel mode of regulation of ABCA1
      by PEST sequence-mediated calpain proteolysis that appears to be reversed by
      apolipoprotein-mediated phospholipid efflux. Inhibition of ABCA1 degradation by
      calpain could represent a novel therapeutic approach to increasing macrophage
      cholesterol efflux and decreasing atherosclerosis.

PMID- 12511594
TI  - src homology 2 domain-containing tyrosine phosphatase SHP-1 controls the
      development of allergic airway inflammation.
AB  - Th2 cells are generated from naive CD4 T cells upon T cell receptor (TCR)
      recognition of antigen and IL-4 stimulation and play crucial roles in humoral
      immunity against infectious microorganisms and the pathogenesis of allergic and
      autoimmune diseases. A tyrosine phosphatase, SHP-1, that contains src homology 2
      (SH2) domains is recognized as a negative regulator for various intracellular
      signaling molecules, including those downstream of the TCR and the IL-4 receptor.
      Here we assessed the role of SHP-1 in Th1/Th2 cell differentiation and in the
      development of Th2-dependent allergic airway inflammation by using a natural SHP
      1 mutant, the motheaten mouse. CD4 T cells appear to develop normally in the
      heterozygous motheaten (me/+) thymus even though they express decreased amounts
      of SHP-1 (about one-third the level of wild-type thymus). The me/+ naive splenic
      CD4 T cells showed enhanced activation by IL-4 receptor-mediated signaling but
      only marginal enhancement of TCR-mediated signaling. Interestingly, the
      generation of Th2 cells was increased and specific cytokine production of mast
      cells was enhanced in me/+ mice. In an OVA-induced allergic airway inflammation
      model, eosinophilic inflammation, mucus hyperproduction, and airway
      hyperresponsiveness were enhanced in me/+ mice. Thus, SHP-1 may have a role as a
      negative regulator in the development of allergic responses, such as allergic
      asthma.

PMID- 12511595
TI  - Novel transglutaminase inhibitors reverse the inflammation of allergic
      conjunctivitis.
AB  - Steroidal anti-inflammatory drugs induce proteins that inhibit phospholipase A(2)
      (PLA(2)), including uteroglobin and lipocortin-1 (annexin I). Uteroglobin and
      lipocortin-1 retain several conserved sequences. Based on these sequences,
      several nonapeptides (antiflammins) were synthesized. These nonapeptides were
      shown to have anti-inflammatory effects in vitro and in vivo, possibly by
      inhibiting PLA(2). Subsequent research showed that PLA(2) is activated by
      transglutaminase 2 (TGase 2). We hypothesize here that TGase 2 inhibitors may
      increase the anti-inflammatory efficacy of inhibiting PLA(2) activity. To test
      this theory, we constructed recombinant peptides containing sequences from pro
      elafin (for inhibition of TGase 2), and from lipocortin-1, lipocortin-5, and
      uteroglobin (for inhibition of PLA(2)). The recombinant peptides, which had dual
      inhibitory effects on purified TGase 2 and PLA(2), reversed the inflammation of
      allergic conjunctivitis to ragweed in a guinea pig model. The present work
      suggests that novel recombinant peptides may be safe and effective agents for the
      treatment of various inflammatory diseases.

PMID- 12511596
TI  - Massive hepatic apoptosis associated with TGF-beta1 activation after Fas ligand
      treatment of IGF binding protein-1-deficient mice.
AB  - Acute liver failure caused by viral hepatitis or toxic damage involves both
      apoptotic and necrotic pathways. IGF binding protein-1 (IGFBP-1), a hepatocyte
      derived secreted protein, is required for normal liver regeneration. To determine
      whether IGFBP-1 could prevent liver injury that entails direct stimulation of
      hepatocyte apoptosis, IGFBP-1(-/-) mice, IGFBP-1(+/+) mice, and mice pretreated
      with Ab's against IGFBP-1 were treated with a normally sublethal dose of Fas
      agonist. IGFBP-1 deficiency was associated with massive hepatocyte apoptosis and
      caspase activation within 3 hours of Fas agonist treatment, which could be
      corrected by pretreatment with IGFBP-1. IGFBP-1-deficient livers had enhanced
      signaling via the integrin receptor at early times (0.5 to 1 hour) after Fas
      agonist treatment accompanied by elevated activated matrix metalloproteinase-9
      (MMP-9), a known target of fibronectin signaling and activator of TGF-beta.
      Within 3 hours of Fas agonist treatment, elevated expression of active TGF-beta1,
      a hepatocyte apoptogen, was observed in IGFBP-1-deficient livers that correlated
      with the appearance of the apoptotic process. Both MMP-9 and TGF-beta1 expression
      were suppressed by IGFBP-1 treatment, supporting their role in the apoptotic
      process. IGFBP-1(-/-) mice also displayed increased injury in a toxic hepatic
      injury model caused by CCl(4). These findings indicate that IGFBP-1 functions as
      a critical hepatic survival factor in the liver by reducing the level of
      proapoptotic signals.

PMID- 12511597
TI  - Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts
      with DAZ (Deleted in AZoospermia) and DAZ-like proteins.
AB  - Early in development, a part of the embryo is set aside to become the germ cell
      lineage that will ultimately differentiate to form sperm and eggs and transmit
      genetic information to the next generation. Men with deletions encompassing the Y
      chromosome DAZ genes have few or no germ cells but are otherwise healthy,
      indicating they harbor specific defects in formation or maintenance of germ
      cells. A DAZ homolog, DAZL (DAZ-Like), is found in diverse organisms, including
      humans and is required for germ cell development in males and/or females. We
      identified proteins that interact with DAZ proteins to better understand their
      function in human germ cells. Here, we show that PUM2, a human homolog of
      Pumilio, a protein required to maintain germ line stem cells in Drosophila and
      Caenorhabditis elegans, forms a stable complex with DAZ through the same
      functional domain required for RNA binding, protein-protein interactions and
      rescue of Pumilio mutations in flies. We also show that PUM2 is expressed
      predominantly in human embryonic stem cells and germ cells and colocalizes with
      DAZ and DAZL in germ cells. These data implicate PUM2 as a component of conserved
      cellular machinery that may be required for germ cell development.

PMID- 12511598
TI  - Ku is required for telomeric C-rich strand maintenance but not for end-to-end
      chromosome fusions in Arabidopsis.
AB  - Telomere dysfunction arising from mutations in telomerase or in telomere capping
      proteins leads to end-to-end chromosome fusions. Paradoxically, the Ku7080
      heterodimer, essential for nonhomologous end-joining double-strand break repair,
      is also found at telomeres, and in mammals it is required to prevent telomere
      fusion. Previously, we showed that inactivation of Ku70 in Arabidopsis results in
      telomere lengthening. Here, we have demonstrated that this telomere elongation is
      telomerase dependent. Further, we found that the terminal 3' G overhang was
      significantly extended in ku70 mutants and in plants deficient in both Ku70 and
      the catalytic subunit of telomerase (TERT), implying that Ku is needed for proper
      maintenance of the telomeric C-rich strand. Consistent with inefficient C-strand
      maintenance, telomere shortening was accelerated in ku70 tert double mutants, and
      the onset of a terminal sterile phenotype was reached two to three times faster
      than in tert single mutants. Unexpectedly, abundant anaphase bridges were found
      in terminal plants harboring critically shortened telomeres, indicating that Ku
      is not required for the formation of end-to-end chromosome fusions in telomerase
      deficient Arabidopsis. Together, these findings define Ku70 as a gene in higher
      eukaryotes required for maintenance of the telomeric C-rich strand and underscore
      the complexity and diversity of molecular interactions at telomeres.

PMID- 12511599
TI  - Induction of neural crest in Xenopus by transcription factor AP2alpha.
AB  - We report experiments with Xenopus laevis, using both intact embryos and
      ectodermal explants, showing that the transcription factor AP2alpha is positively
      regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this
      activation is an essential step in the induction of neural crest (NC). Ectopic
      expression of AP2alpha is sufficient to activate high-level expression of NC
      specific genes such as Slug and Sox9, which can occur as isolated domains within
      the neural plate as well as by expansion of endogenous NC territories. AP2alpha
      also has the property of inducing NC in isolated ectoderm in which Wnt signaling
      is provided but BMP signaling is minimized by overexpression of chordin. Like
      other NC regulatory factors, activation of AP2alpha requires some attenuation of
      endogenous BMP signaling; however, this process occurs at a lower threshold for
      AP2alpha. Furthermore, AP2alpha expression domains are larger than for other NC
      factors. Loss-of-function experiments with antisense AP2alpha morpholino
      oligonucleotides result in severe reduction in the NC territory. These results
      support a central role for AP2alpha in NC induction. We propose a model in which
      AP2alpha expression, along with inactivation of NC inhibitory factors such as
      Dlx3, establish a feedback loop comprising AP2alpha, Sox9, and Slug, leading to
      and maintaining NC specification.

PMID- 12511600
TI  - Extensive and specific responses of a eukaryote to bacterial quorum-sensing
      signals.
AB  - Many bacteria use N-acyl homoserine lactone (AHL) signals to coordinate the
      behavior of individual cells in a local population. The successful infection of
      eukaryotic hosts by bacteria seems to depend particularly on such AHL-mediated
      "quorum-sensing" regulation. We have used proteome analysis to show that a
      eukaryotic host, the model legume Medicago truncatula, is able to detect
      nanomolar to micromolar concentrations of bacterial AHLs from both symbiotic
      (Sinorhizobium meliloti) and pathogenic (Pseudomonas aeruginosa) bacteria, and
      that it responds in a global manner by significant changes in the accumulation of
      over 150 proteins, 99 of which have been identified by peptide mass
      fingerprinting. The accumulation of specific proteins and isoforms depended on
      AHL structure, concentration, and time of exposure. AHLs were also found to
      induce tissue-specific activation of beta-glucuronidase (GUS) reporter fusions to
      an auxin-responsive and three chalcone synthase promoters, consistent with AHL
      induced changes in the accumulation of auxin-responsive and flavonoid synthesis
      proteins. In addition, exposure to AHLs was found to induce changes in the
      secretion of compounds by the plants that mimic quorum-sensing signals and thus
      have the potential to disrupt quorum sensing in associated bacteria. Our results
      indicate that eukaryotes have an extensive range of functional responses to AHLs
      that may play important roles in the beneficial or pathogenic outcomes of
      eukaryote-prokaryote interactions.

PMID- 12511601
TI  - Transactivation functions of the N-terminal domains of nuclear hormone receptors:
      protein folding and coactivator interactions.
AB  - The N-terminal domains (NTDs) of many members of the nuclear hormone receptor
      (NHR) family contain potent transcription-activating functions (AFs). Knowledge
      of the mechanisms of action of the NTD AFs has lagged, compared with that
      concerning other important domains of the NHRs. In part, this is because the NTD
      AFs appear to be unfolded when expressed as recombinant proteins. Recent studies
      have begun to shed light on the structure and function of the NTD AFs.
      Recombinant NTD AFs can be made to fold by application of certain osmolytes or
      when expressed in conjunction with a DNA-binding domain by binding that DNA
      binding domain to a DNA response element. The sequence of the DNA binding site
      may affect the functional state of the AFs domain. If properly folded, NTD AFs
      can bind certain cofactors and primary transcription factors. Through these,
      and/or by direct interactions, the NTD AFs may interact with the AF2 domain in
      the ligand binding, carboxy-terminal portion of the NHRs. We propose models for
      the folding of the NTD AFs and their protein-protein interactions.

PMID- 12511603
TI  - A central role for Ets-2 in the transcriptional regulation and cyclic adenosine
      5'-monophosphate responsiveness of the human chorionic gonadotropin-beta subunit
      gene.
AB  - Ets-2 has an important role in controlling the differentiation of the placenta.
      Here we show by truncation and mutational analysis that two closely spaced Ets-2
      binding sites in the proximal promoter of the human chorionic gonadotropin beta5
      (hCGbeta5) gene constitute a major enhancer for hCGbeta gene expression in JAr
      and JEG-3 human choriocarcinoma cells and in mouse NIH3T3 cells. Contrary to a
      previous report, we also demonstrate that the ability of Ets-2 to enhance
      transcription is subject to control by the Ras/MAPK pathway, although this
      relationship is less easily demonstrable in JAr and JEG-3 choriocarcinoma cells
      than in the 3T3 cells because the former already possess a fully activated MAPK
      pathway and contain Ets-2 phosphorylated at threonine residue at T72.
      Coexpression of Ets-2 and activated Ras in 3T3 cells led to activation of
      MAPK/ERK kinase 1/2, phosphorylation of Ets-2 at T72, and an approximately 120
      fold up-regulation of reporter gene expression from a short (-175) hCGbeta
      promoter. Fold activation in JAr and JEG-3 cells was rather less (20- to 30
      fold), but basal activity was much higher. These effects on promoter activity
      were largely reversed in presence of the MAPK inhibitor PD98059, which prevents
      ERK1/2 activation, and partially reversed by mutating T72 on Ets-2. We finally
      show that the ability of 8-bromoadenosine-cAMP to stimulate hCGbeta promoter
      activity in JAr and JEG-3 cells occurs with a short promoter lacking the upstream
      elements previously considered to be essential for cAMP activation of the gene
      and, through mutational analysis, confirm that the major cAMP effects on the
      hCGbeta promoter are mediated through the proximal Ets-2 enhancer. The data are
      consistent with the hypothesis that Ets-2 has a general and possibly essential
      role in controlling the activity of genes associated with trophectoderm
      differentiation.

PMID- 12511604
TI  - Trapping and characterization of novel retinoid response elements.
AB  - Retinoids, such as retinoic acid (RA), play a critical role in normal vertebrate
      development and physiology. However, embryonic exposure to excess retinoids also
      causes severe malformations. Retinoids bind RA receptors and retinoid X
      receptors, thus activating a plethora of genes. Separating the genes induced
      directly by retinoid-bound receptors from those induced subsequently by other
      transcription factors is difficult. The loose consensus defining known RA
      responsive elements (RAREs) further complicates this effort. We developed a yeast
      based system to trap functional RAREs in the mouse genome. Several of the clones
      contain RAREs near RA-induced genes. Mammalian reporter gene analyses and EMSAs
      showed that these are bona fide RAREs. This functional genomics approach should
      identify RA-regulated genes that initiate critical signaling cascades in cells.

PMID- 12511605
TI  - Transcriptional analysis of the orphan nuclear receptor constitutive androstane
      receptor (NR1I3) gene promoter: identification of a distal glucocorticoid
      response element.
AB  - The constitutive androstane receptor (CAR, NR1I3) transcriptionally activates
      cytochrome P450 2B6, 2C9, and 3A4 when activated by xenobiotics, such as
      phenobarbital. Information on the human CAR promoter was obtained by searching
      the NCBI human genome database. A contig (NT026945) corresponding to a fragment
      of chromosome 1q21 was found to contain the complete CAR gene. These data were
      confirmed using chromosomal in situ hybridization. Both primer extension and 5'
      rapid amplification of the cDNA end PCR analysis were carried out to determine
      the transcriptional start site of human CAR, which was found to be 32 nucleotides
      downstream of a potential TATA box (CATAAAA). In addition, we found that the 5'
      untranslated region of CAR mRNA is 110 nucleotides shorter than previously
      reported. Using genomic PCR, we amplified and cloned approximately 4.9 kb (
      4711/+144) of the CAR gene promoter. The activity of this promoter was measured
      by transient transfection. Deletion analysis suggested the presence of a
      glucocorticoid responsive element in its distal region (-4477/-4410). From
      cotransfection experiments, mutagenesis, and gel shift assays, we identified a
      glucocorticoid response element at -4447/-4432 that was recognized and
      transactivated by the human glucocorticoid receptor. Finally, using the chromatin
      immunoprecipitation assay, we demonstrated that the glucocorticoid receptor binds
      to the distal region of CAR promoter in cultured hepatocytes only in the presence
      of dexamethasone. Identification of this functional element provides a rational
      mechanistic basis for CAR induction by glucocorticoids. CAR appears to be a
      primary glucocorticoid receptor-response gene.

PMID- 12511606
TI  - Estrogens activate bone morphogenetic protein-2 gene transcription in mouse
      mesenchymal stem cells.
AB  - Estrogens exert their physiological effects on target tissues by interacting with
      the estrogen receptors, ERalpha and ERbeta. Estrogen replacement is one the most
      common and effective strategies used to prevent osteoporosis in postmenopausal
      women. Whereas it was thought that estrogens work exclusively by inhibiting bone
      resorption, our previous results show that 17beta-estradiol (E2) increases mouse
      bone morphogenetic protein (BMP)-2 mRNA, suggesting that estrogens may also
      enhance bone formation. In this study, we used quantitative real-time RT-PCR
      analysis to demonstrate that estrogens increase BMP-2 mRNA in mouse mesenchymal
      stem cells. The selective ER modulators, tamoxifen, raloxifene, and ICI-182,780
      (ICI), failed to enhance BMP-2 mRNA, whereas ICI inhibited E2 stimulation of
      expression. To investigate if estrogens increase BMP-2 expression by
      transcriptional mechanisms and if the response is mediated by ERalpha and/or
      ERbeta, we studied the effects of estrogens on BMP-2 promoter activity in
      transient transfected C3H10T1/2 cells. E2 produced a dose-dependent induction of
      the mouse -2712 BMP-2 promoter activity in cells cotransfected with ERalpha and
      ERbeta. At a dose of 10 nM E2, ERalpha induced mouse BMP-2 promoter activity 9
      fold, whereas a 3-fold increase was observed in cells cotransfected with ERbeta.
      Tamoxifen and raloxifene were weak activators of the mouse BMP-2 promoter via
      ERalpha, but not via ERbeta. ICI blocked the activation of BMP-2 promoter
      activity by E2 acting via both ERalpha and ERbeta, indicating that mouse BMP-2
      promoter activation is ER dependent. In contrast to E2 and selective ER
      modulators, the phytoestrogen, genistein was more effective at activating the
      mouse BMP-2 promoter with ERbeta, compared with ERalpha. Using a deletion series
      of the BMP-2 promoter, we determined that AP-1 or Sp1 sites are not required for
      E2 activation. A mutation in a sequence at -415 to -402 (5'-GGGCCActcTGACCC-3')
      that resembles the classical estrogen-responsive element abolished the activation
      of the BMP-2 promoter in response to E2. Our studies demonstrate that E2
      activation of mouse BMP-2 gene transcription requires ERalpha or ERbeta acting
      via a variant estrogen-responsive element binding site in the promoter, with
      ERalpha being the more efficacious regulator. Estrogenic compounds may enhance
      bone formation by increasing the transcription of the BMP-2 gene.

PMID- 12511607
TI  - A novel estrogen receptor alpha-associated protein, template-activating factor
      Ibeta, inhibits acetylation and transactivation.
AB  - Estrogen receptor-alpha (ERalpha) functions as a ligand-activated transcription
      factor that alters expression of estrogen-responsive genes in target cells.
      Numerous regulatory proteins interact with ERalpha to influence estrogen-mediated
      transactivation. We have identified a novel coregulatory protein, template
      activating factor-Ibeta (TAF-Ibeta), which binds to ERalpha in vitro when the
      receptor is not complexed with an estrogen response element. The central region
      of TAF-Ibeta interacts with both the DNA-binding domain and the carboxy-terminal
      region of ERalpha. Coimmunoprecipitation experiments demonstrate that TAF-Ibeta
      is associated with the unoccupied, but not the estrogen-occupied, ERalpha in MCF
      7 breast cancer cells. Overexpression of TAF-Ibeta inhibits ERalpha-mediated
      transcription in a dose- dependent manner. TAF-Ibeta represses p300-mediated
      acetylation of histones and ERalpha in vitro and decreases ERalpha acetylation in
      vivo. TAF-Ibeta also binds to other nuclear receptor superfamily members and
      represses thyroid hormone receptor beta- induced transcription in transient
      transfection assays. Taken together, these data provide evidence that TAF-Ibeta
      regulates transcription of estrogen- responsive genes by modulating acetylation
      of histones and ERalpha and that the effects of TAF-Ibeta extend to other nuclear
      receptor superfamily members as well.

PMID- 12511608
TI  - Hormone-dependent repression of the E2F-1 gene by thyroid hormone receptors.
AB  - Thyroid hormone induces differentiation of many different tissues in mammals,
      birds, and amphibians. The different tissues all differentiate from proliferating
      precursor cells, and the normal cell cycle is suspended while cells undergo
      differentiation. We have investigated how thyroid hormone affects the expression
      of the E2F-1 protein, a key transcription factor that controls G1- to S-phase
      transition. We show that during thyroid hormone-induced differentiation of
      embryonic carcinoma cells and of oligodendrocyte precursor cells, the levels of
      E2F-1 mRNA and E2F-1 protein decrease. This is caused by the thyroid hormone
      receptor (TR) regulating the transcription of the E2F-1 gene. The TR binds
      directly to a negative thyroid hormone response element, called the Z-element, in
      the E2F-1 promoter. When bound, the TR activates transcription in the absence of
      ligand but represses transcription in the presence of ligand. In addition,
      liganded TR represses transcription of the S-phase-specific DNA polymerase alpha,
      thymidine kinase, and dihydropholate reductase genes. These results suggest that
      thyroid hormone-induced withdrawal from the cell cycle takes place through the
      repression of S-phase genes. We suggest that this is an initial and crucial step
      in thyroid hormone-induced differentiation of precursor cells.

PMID- 12511609
TI  - Somatostatin receptor subtype 5 regulates insulin secretion and glucose
      homeostasis.
AB  - Somatostatin (SRIF) regulates pancreatic insulin and glucagon secretion. In the
      present study we describe the generation of SRIF receptor subtype 5 knockout
      (sst(5) KO) mice to examine the role of SRIF receptor subtypes (sst) in
      regulating insulin secretion and glucose homeostasis. Mice deficient in sst(5)
      were viable, fertile, appeared healthy, and displayed no obvious phenotypic
      abnormalities. Pancreatic islets isolated from sst(5) KO mice displayed increased
      total insulin content as compared with islets obtained from wild-type (WT) mice.
      Somatostatin-28 (SRIF-28) and the sst(5)/sst(1)-selective agonist compound 5/1
      potently inhibited glucose-stimulated insulin secretion from WT islets. SRIF-28
      inhibited insulin secretion from sst(5) KO islets with 16-fold less potency while
      the maximal effect of compound 5/1 was markedly diminished when compared with its
      effects in WT islets. sst(5) KO mice exhibited decreased blood glucose and plasma
      insulin levels and increased leptin and glucagon concentrations compared with WT
      mice. Furthermore, sst(5) KO mice displayed decreased susceptibility to high fat
      diet-induced insulin resistance. The results of these studies suggest sst(5)
      mediates SRIF inhibition of pancreatic insulin secretion and contributes to the
      regulation of glucose homeostasis and insulin sensitivity. Our findings suggest a
      potential beneficial role of sst(5) antagonists for alleviating metabolic
      abnormalities associated with obesity and insulin resistance.

PMID- 12511610
TI  - Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced
      corepressor release exhibit decreased stability in the N-terminal ligand-binding
      domain.
AB  - Resistance to thyroid hormone (RTH) syndrome is associated with mutations in the
      human thyroid hormone receptor-beta (hTRbeta), many of which show marked
      reduction in hormone binding. Here, we investigated the structural consequences
      of two RTH mutants (A234T and R243Q), residing in the flexible N-terminal portion
      of the ligand binding domain (LBD), which exhibit modestly reduced hormone
      binding with impaired release of corepressor. X-ray crystallography analyses
      revealed that these two RTH mutants modulate the position of this flexible region
      by either altering the movement of helix 1 (A234T) or disrupting a salt bridge
      (R243Q). The subsequent increased flexibility and mobility in regions after the
      two sites of mutation coincided with a disorganized LBD. Consistent with this
      finding, the ability of these mutant N-terminal regions (234-260) to recruit the
      remaining LBD was decreased in a ligand-dependent helix assembly assay.
      Collectively, these data suggest that structural information imparted by the
      flexible segment in the N-terminal LBD is critical for overall stability of the
      LBD. Thus, these structural analyses provide mechanistic insight into the
      etiology of RTH disease in human TRbeta mutants that exhibit hormone binding with
      decreased ligand-dependent corepressor release.

PMID- 12511611
TI  - A nonsteroidal glucocorticoid receptor antagonist.
AB  - Selective intracellular receptor antagonists are used clinically to ameliorate
      hormone-dependent disease states. Patients with Cushing's syndrome have high
      levels of the glucocorticoid, cortisol, and suffer significant consequences from
      this overexposure. High levels of this hormone are also implicated in
      exacerbating diabetes and the stress response. Selectively inhibiting this
      hormone may have clinical benefit in these disease states. To this end, we have
      identified the first selective, nonsteroidal glucocorticoid receptor (GR)
      antagonist. This compound is characterized by a tri-aryl methane core chemical
      structure. This GR-specific antagonist binds with nanomolar affinity to the GR
      and has no detectable binding affinity for the highly related receptors for
      mineralocorticoids, androgens, estrogens, and progestins. We demonstrate that
      this antagonist inhibits glucocorticoid-mediated transcriptional regulation. This
      compound binds competitively with steroids, likely occupying a similar site
      within the ligand-binding domain. Once bound, however, the compound fails to
      induce critical conformational changes in the receptor necessary for agonist
      activity.

PMID- 12511612
TI  - Role of the promyelocytic leukemia body in the dynamic interaction between the
      androgen receptor and steroid receptor coactivator-1 in living cells.
AB  - The dynamic interaction between the androgen receptor (AR) and steroid receptor
      coactivator-1 (SRC-1) was explored in living cells expressing chimeric forms of
      the receptor and the coactivator containing two spectral variants of jellyfish
      fluorescent protein. Laser scanning confocal imaging of transfected cells
      expressing fluorescently labeled SRC-1 revealed that in an unsynchronized cell
      population, the coactivator is distributed in approximately 40% cells as nuclear
      bodies of 0.2-1.0 microm in diameter. Immunostaining of cyan fluorescent protein
      labeled SRC-1 (CFP-SRC1)-expressing cells with antibody to promyelocytic leukemia
      (PML) protein showed significant overlap of the CFP fluorescence with the
      antibody stain. Cotransfection of cells with a plasmid expressing the CFP
      conjugate of Sp100 (another marker protein for the PML nuclear body) also showed
      colocalization of the yellow fluorescent protein (YFP)-SRC1 containing nuclear
      foci with the PML bodies in living cells. Analysis of the three-dimensional
      structure revealed that the PML bodies are round to elliptical in shape with
      multiple satellite bodies on their surface. Some of these satellite bodies
      contain the SRC-1. Activation and nuclear import of CFP-AR by the agonistic
      ligand 5alpha-dihydrotestosterone, but not by the antagonist casodex, transferred
      YFP-SRC1 from the PML bodies to an interlacing filamentous structure. In a single
      living cell, agonist-activated AR caused a time-dependent movement of YFP-SRC1
      from the PML bodies to this filamentous structure. Additionally, coexpression of
      a constitutively active mutant of AR (AR-deltaligand binding domain) also
      displaced YFP-SRC1 from the PML bodies to this intranuclear filamentous
      structure. The fluorescence recovery after photobleaching approach was used to
      examine changes in the kinetics of movement of YFP-SRC1 during its mobilization
      from the PML bodies to the intranuclear filamentous structure by the agonist
      activated AR. Results of the relative half-times (t(1/2)) of replacement of YFP
      SRC1 within the photobleached region of a single PML body from its surrounding
      nuclear space supported the conclusion that SRC-1 is actively transported from
      the PML bodies to the intranuclear filamentous structure by the ligand-activated
      AR. This observation also suggests an interaction between AR and SRC-1 before its
      binding to the target gene. The PML bodies have been implicated as a cross-road
      for multiple regulatory pathways that control cell proliferation, cellular
      senescence, and apoptosis. Our present results along with other recent reports
      expand the role of this subnuclear structure to include the regulation of steroid
      hormone action.

PMID- 12511614
TI  - No circadian rhythms in testis: Period1 expression is clock independent and
      developmentally regulated in the mouse.
AB  - Spermatogenesis is a process whereby haploid spermatozoa differentiate through
      meiosis from precursor stem cells. We examined the expression of circadian clock
      genes in the testis, to assess clock control over the timing of different
      developmental events. Clock genes are known to oscillate with circadian
      rhythmicity in the central clock structure, the suprachiasmatic nucleus of the
      hypothalamus, but also in peripheral tissues. Here we show that Per1 gene
      expression in the testis is constant over a 24-h period and that the Per1
      transcript is expressed at a level higher than the peak values of the Per1
      oscillations observed for other tissues. Bmal1, another clock gene whose
      expression oscillates in other tissues, also shows constant expression levels in
      the testis. In addition, the levels and phosphorylation state of the PER1 protein
      are not oscillating at all times of day. Strikingly, Per1 is restricted primarily
      to step 7 to 10 spermatids and thus appears to be developmentally regulated. The
      expression of the Clock transcript is also developmentally regulated, but it is
      found principally in spermatogonia and spermatocytes up until the time of the
      first meiotic division. Per1 expression is not altered in testes from Clock
      mutant mice, suggesting that CLOCK does not activate Per1 in male germ cells, in
      contrast to what it does in other mouse tissues. Taken together, our observations
      suggest that the testis, in contrast to all other peripheral tissues, lacks a
      functioning circadian clock.

PMID- 12511615
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 12511617
TI  - Happy new year.

PMID- 12511618
TI  - Intellectual property. Universities ask Supreme Court to reverse patent ruling.

PMID- 12511619
TI  - U.S. Congress. New Senate leader no stranger to science policy.

PMID- 12511620
TI  - Animal behavior. Orangutans, like chimps, heed the cultural call of the
      collective.

PMID- 12511621
TI  - Japan. Science fares well in a tight budget.

PMID- 12511622
TI  - Human subjects. Crossing a frontier: research on the dead.

PMID- 12511623
TI  - China. With help from overseas Chinese, a Western-style institute takes shape.

PMID- 12511624
TI  - Scientific misconduct. More of Bell Labs physicist's papers retracted.

PMID- 12511625
TI  - German science. Stem cell project wins final approval.

PMID- 12511626
TI  - Developmental biology. Newborn neurons search for meaning.

PMID- 12511627
TI  - Mantle dynamics. Plumes from the core lost and found.

PMID- 12511628
TI  - Physics. Researchers race to put the quantum into mechanics.

PMID- 12511629
TI  - Climate change. Consensus on ecological impacts remains elusive.

PMID- 12511630
TI  - Microbicides. Raising new barriers against HIV infection.

PMID- 12511631
TI  - Perceptions of science. Beyond the visible--microscopy, nature, and art.

PMID- 12511632
TI  - Ecology. Why gobies are like Hobbits.

PMID- 12511633
TI  - Astrophysics. When a white dwarf explodes.

PMID- 12511634
TI  - Neuroscience. To see is to attend.

PMID- 12511635
TI  - Ecology. Social slime molds meet their match.

PMID- 12511636
TI  - Glaciology. An ice sheet remembers.

PMID- 12511638
TI  - The Milky Way's restless swarms of stars.

PMID- 12511639
TI  - Breaking up is easy to do.

PMID- 12511640
TI  - Outside sources frame a galactic puzzle.

PMID- 12511641
TI  - Age estimates of globular clusters in the Milky Way: constraints on cosmology.
AB  - Recent observations of stellar globular clusters in the Milky Way Galaxy,
      combined with revised ranges of parameters in stellar evolution codes and new
      estimates of the earliest epoch of globular cluster formation, result in a 95%
      confidence level lower limit on the age of the Universe of 11.2 billion years.
      This age is inconsistent with the expansion age for a flat Universe for the
      currently allowed range of the Hubble constant, unless the cosmic equation of
      state is dominated by a component that violates the strong energy condition. This
      means that the three fundamental observables in cosmology-the age of the
      Universe, the distance-redshift relation, and the geometry of the Universe-now
      independently support the case for a dark energy-dominated Universe.

PMID- 12511642
TI  - Genesis of the heaviest elements in the Milky Way Galaxy.
AB  - We review the origin and evolution of the heavy elements, those with atomic
      numbers greater than 30, in the early history of the Milky Way. There is a large
      star-to-star bulk scatter in the concentrations of heavy elements with respect to
      the lighter metals, which suggests an early chemically unmixed and inhomogeneous
      Galaxy. The relative abundance patterns among the heavy elements are often very
      different from the solar system mix, revealing the characteristics of the first
      element donors in the Galaxy. Abundance comparisons among several halo stars show
      that the heaviest neutron-capture elements (including barium and heavier) are
      consistent with a scaled solar system rapid neutron-capture abundance
      distribution, whereas the lighter such elements do not conform to the solar
      pattern. The stellar abundances indicate an increasing contribution from the slow
      neutron-capture process (s-process) at higher metallicities in the Galaxy. The
      detection of thorium in halo and globular cluster stars offers a promising,
      independent age-dating technique that can put lower limits on the age of the
      Galaxy.

PMID- 12511643
TI  - Synthesis of serotonin by a second tryptophan hydroxylase isoform.

PMID- 12511644
TI  - Neuronal activity in the lateral intraparietal area and spatial attention.
AB  - Although the parietal cortex has been implicated in the neural processes
      underlying visual attention, the nature of its contribution is not well
      understood. We tracked attention in the monkey and correlated the activity of
      neurons in the lateral intraparietal area (LIP) with the monkey's attentional
      performance. The ensemble activity in LIP across the entire visual field
      describes the spatial and temporal dynamics of a monkey's attention. Activity
      subtending a single location in the visual field describes the attentional
      priority at that area but does not predict that the monkey will actually attend
      to or make an eye movement to that location.

PMID- 12511645
TI  - Dependence of upper critical field and pairing strength on doping in cuprates.
AB  - We have determined the upper critical field Hc2 as a function of hole
      concentration in bismuth-based cuprates by measuring the voltage induced by
      vortex flow in a driving temperature gradient (the Nernst effect), in magnetic
      fields up to 45 tesla. We found that Hc2 decreased steeply as doping increased,
      in both single and bilayer cuprates. This relationship implies that the Cooper
      pairing potential displays a trend opposite to that of the superfluid density
      versus doping. The coherence length of the pairs xi(0) closely tracks the gap
      measured by photoemission. We discuss implications for understanding the doping
      dependence of the critical temperature Tc0.

PMID- 12511646
TI  - Three-dimensional mapping of dislocation avalanches: clustering and space/time
      coupling.
AB  - There is growing evidence for the complex, intermittent, and heterogeneous
      character of plastic flow. Here we report a three-dimensional mapping of
      dislocation avalanches during creep deformation of an ice crystal, from a
      multiple-transducers acoustic emission analysis. Correlation analysis shows that
      dislocation avalanches are spatially clustered according to a fractal pattern and
      that the closer in time two avalanches are, the larger the probability is that
      they will be closer in space. Such a space/time coupling may contribute to the
      self-organization of the avalanches into a clustered pattern.

PMID- 12511647
TI  - Phengite-based chronology of K- and Ba-rich fluid flow in two paleosubduction
      zones.
AB  - Subduction recycles aqueous fluids from slab and sediment to the mantle.
      Subduction zones are long-lived, but time scales for fluid-rock interaction
      within subduction complexes are uncertain. Large-ion lithophile elements
      (potassium and barium) were added to eclogite (subducted basalt) during high
      pressure/temperature metamorphism via phengite crystallization from subduction
      zone fluids. Phengite grains from eclogite blocks and their metasomatic selvages
      yielded 40Ar/39Ar ages across grains and between samples that indicate 25 and 60
      million years of fluid-rock interaction in the Samana Complex, Dominican
      Republic, and the Franciscan Complex, California, respectively.

PMID- 12511648
TI  - Holocene deglaciation of Marie Byrd Land, West Antarctica.
AB  - Surface exposure ages of glacial deposits in the Ford Ranges of western Marie
      Byrd Land indicate continuous thinning of the West Antarctic Ice Sheet by more
      than 700 meters near the coast throughout the past 10,000 years. Deglaciation
      lagged the disappearance of ice sheets in the Northern Hemisphere by thousands of
      years and may still be under way. These results provide further evidence that
      parts of the West Antarctic Ice Sheet are on a long-term trajectory of decline.
      West Antarctic melting contributed water to the oceans in the late Holocene and
      may continue to do so in the future.

PMID- 12511649
TI  - Orangutan cultures and the evolution of material culture.
AB  - Geographic variation in some aspects of chimpanzee behavior has been interpreted
      as evidence for culture. Here we document similar geographic variation in
      orangutan behaviors. Moreover, as expected under a cultural interpretation, we
      find a correlation between geographic distance and cultural difference, a
      correlation between the abundance of opportunities for social learning and the
      size of the local cultural repertoire, and no effect of habitat on the content of
      culture. Hence, great-ape cultures exist, and may have done so for at least 14
      million years.

PMID- 12511650
TI  - Single-gene greenbeard effects in the social amoeba Dictyostelium discoideum.
AB  - Selection can favor reproductive altruism if an altruism allele aids copies of
      itself by helping relatives. The alternative "greenbeard" mechanism, in which an
      allele directly recognizes and aids copies of itself in others, is generally
      thought to be too complex for a single gene to carry out. The csA gene in
      Dictyostelium discoideum acts as a single-gene greenbeard. When wild-type cells
      are mixed with csA-knockout cells, the wild type is more altruistic, but is also
      able preferentially to direct the benefits to other wild-type cells. Both
      properties derive directly from homophilic cell adhesion of the protein encoded
      by csA.

PMID- 12511651
TI  - Genetic evidence for local retention of pelagic larvae in a Caribbean reef fish.
AB  - The pelagic larvae of many marine organisms can potentially disperse across
      hundreds of kilometers, but whether oceanographic or behavioral mechanisms can
      constrain dispersal over periods sufficient for the evolution of genetic
      differentiation remains unclear. Here, we concurrently examine larval duration
      and genetic population differentiation in a cleaner goby, Elacatinus evelynae, a
      member of the most species-rich genus of Caribbean reef fishes. Despite evidence
      for extended pelagic duration (21 days), populations of E. evelynae show strong
      genetic differentiation: among color forms (1.36 to 3.04% divergent at
      mitochondrial cytochrome b) and among island populations within color forms
      (Phi(ST) up to 70%). These results suggest that marine populations can remain
      demographically closed for thousands of generations despite extended larval
      duration, and that recognition cues such as color may promote speciation when
      geographic barriers are transient or weak.

PMID- 12511652
TI  - Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by
      prolactin.
AB  - Neurogenesis occurs in the olfactory system of the adult brain throughout life,
      in both invertebrates and vertebrates, but its physiological regulation is not
      understood. We show that the production of neuronal progenitors is stimulated in
      the forebrain subventricular zone of female mice during pregnancy and that this
      effect is mediated by the hormone prolactin. The progenitors then migrate to
      produce new olfactory interneurons, a process likely to be important for maternal
      behavior, because olfactory discrimination is critical for recognition and
      rearing of offspring. Neurogenesis occurs even in females that mate with sterile
      males. These findings imply that forebrain olfactory neurogenesis may contribute
      to adaptive behaviors in mating and pregnancy.

PMID- 12511653
TI  - Fluids from aging ocean crust that support microbial life.
AB  - Little is known about the potential for life in the vast, low-temperature (<100
      degrees C) reservoir of fluids within mid-ocean ridge flank and ocean basin
      crust. Recently, an overpressured 300-meter-deep borehole was fitted with an
      experimental seal (CORK) delivering crustal fluids to the sea floor for discrete
      and large-volume sampling and characterization. Results demonstrate that the 65
      degrees C fluids from 3.5-million-year-old ocean crust support microbial growth.
      Ribosomal RNA gene sequence data indicate the presence of diverse Bacteria and
      Archaea, including gene clones of varying degrees of relatedness to known nitrate
      reducers (with ammonia production), thermophilic sulfate reducers, and
      thermophilic fermentative heterotrophs, all consistent with fluid chemistry.

PMID- 12511654
TI  - Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms.
AB  - How scaffold proteins control information flow in signaling pathways is poorly
      understood: Do they simply tether components, or do they precisely orient and
      activate them? We found that the yeast mitogen-activated protein (MAP) kinase
      scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous
      protein interactions could functionally replace native kinase recruitment
      interactions, indicating that simple tethering is largely sufficient for scaffold
      mediated signaling. Moreover, by engineering a scaffold that tethers a unique
      kinase set, we could create a synthetic MAP kinase pathway with non-natural input
      output properties. These findings demonstrate that scaffolds are highly flexible
      organizing factors that can facilitate pathway evolution and engineering.

PMID- 12511655
TI  - Extracting work from a single heat bath via vanishing quantum coherence.
AB  - We present here a quantum Carnot engine in which the atoms in the heat bath are
      given a small bit of quantum coherence. The induced quantum coherence becomes
      vanishingly small in the high-temperature limit at which we operate and the heat
      bath is essentially thermal. However, the phase phi, associated with the atomic
      coherence, provides a new control parameter that can be varied to increase the
      temperature of the radiation field and to extract work from a single heat bath.
      The deep physics behind the second law of thermodynamics is not violated;
      nevertheless, the quantum Carnot engine has certain features that are not
      possible in a classical engine.

PMID- 12511656
TI  - Paucity of genes on the Drosophila X chromosome showing male-biased expression.
AB  - Sex chromosomes are primary determinants of sexual dimorphism in many organisms.
      These chromosomes are thought to arise via the divergence of an ancestral
      autosome pair and are almost certainly influenced by differing selection in males
      and females. Exploring how sex chromosomes differ from autosomes is highly
      amenable to genomic analysis. We examined global gene expression in Drosophila
      melanogaster and report a dramatic underrepresentation of X-chromosome genes
      showing high relative expression in males. Using comparative genomics, we find
      that these same X-chromosome genes are exceptionally poorly conserved in the
      mosquito Anopheles gambiae. These data indicate that the X chromosome is a
      disfavored location for genes selectively expressed in males.

PMID- 12511657
TI  - Radiology 2003--the constancy of change.

PMID- 12511660
TI  - Authors of journal articles and educational materials will have an image license
      from RSNA. Radiological Society of North America.

PMID- 12511661
TI  - Peggy J. Fritzsche, MD, President Radiological Society of North America, 2003.

PMID- 12511662
TI  - Probability in radiology.
AB  - In this article, a summary of the basic rules of probability using examples of
      their application in radiology is presented. Those rules describe how
      probabilities may be combined to obtain the chance of "success" with either of
      two diagnostic or therapeutic procedures or with both. They define independence
      and relate it to the conditional probability. They describe the relationship
      (Bayes rule) between sensitivity, specificity, and prevalence on the one hand and
      the positive and negative predictive values on the other. Finally, the two
      distributions most commonly encountered in statistical models of radiologic data
      are presented: the binomial and normal distributions.

PMID- 12511663
TI  - Researcher contributions and fulfillment of ICMJE authorship criteria: analysis
      of author contribution lists in research articles with multiple authors published
      in radiology. International Committee of Medical Journal Editors.
AB  - PURPOSE: To determine the number of researchers who fulfill the International
      Committee of Medical Journal Editors (ICMJE) authorship criteria and to evaluate
      individual contributions. MATERIALS AND METHODS: The author contribution lists of
      Radiology articles published between 1998 and 2000 with at least three authors
      were reviewed. The fulfillment of ICMJE criteria for authorship and the
      contribution percentage were assessed according to each researcher's position in
      the byline and nationality (American vs international), number of researchers per
      article, and year of publication. RESULTS: Sixty-eight percent of researchers
      fulfilled the ICMJE authorship criteria. Position in the byline indicated a
      significant difference in fulfillment (P <.001): 98.9% and 85.3% for the first
      and second authors, respectively, and 52.8% and 66.5% for the middle and last
      authors, respectively. American researchers had a higher percentage (78%) of
      fulfillment than did international researchers (57%) (P <.001). Fulfillment
      decreased as the number of authors per article increased (P <.001), although
      there was no significant change throughout 1998-2000. The mean contribution
      percentages decreased greatly from first to second to last to middle authors.
      American researchers had a significantly larger mean contribution percentage than
      did international researchers. Of the total 6,686 researchers, 2,316 (35%)
      contributed to one or two categories. This rate was higher for middle and
      international authors. CONCLUSION: The 68% fulfillment of criteria for authorship
      was closely related to the large number of researchers contributing to one
      category or to categories belonging to the same ICMJE criterion.

PMID- 12511664
TI  - Towards complete and accurate reporting of studies of diagnostic accuracy: The
      STARD Initiative.
AB  - OBJECTIVE: To improve the accuracy and completeness of reporting of studies of
      diagnostic accuracy, to allow readers to assess the potential for bias in the
      study and to evaluate its generalisability. METHODS: The Standards for Reporting
      of Diagnostic Accuracy (STARD) steering group searched the literature to identify
      publications on the appropriate conduct and reporting of diagnostic studies and
      extracted potential items into an extensive list. Researchers, editors, and
      members of professional organisations shortened this list during a two-day
      consensus meeting with the goal of developing a checklist and a generic flow
      diagram for studies of diagnostic accuracy. RESULTS: The search for published
      guidelines regarding diagnostic research yielded 33 previously published
      checklists, from which we extracted a list of 75 potential items. At the
      consensus meeting, participants shortened the list to a 25-item checklist, using
      evidence, whenever available. A prototypical flow diagram provides information
      about the method of patient recruitment, the order of test execution and the
      numbers of patients undergoing the test under evaluation, the reference standard
      or both. CONCLUSIONS: Evaluation of research depends on complete and accurate
      reporting. If medical journals adopt the checklist and the flow diagram, the
      quality of reporting of studies of diagnostic accuracy should improve to the
      advantage of the clinicians, researchers, reviewers, journals, and the public.

PMID- 12511665
TI  - Why do some people succeed where others fail? Implications for education.

PMID- 12511666
TI  - Hereditary renal cancers.
AB  - Hereditary renal cancer syndromes can lead to multiple bilateral kidney tumors
      that occur at a younger age than do nonhereditary renal cancers. Imaging plays an
      important role in the diagnosis and management of these syndromes. During the
      past decade, several new hereditary renal syndromes have been discovered but are
      not yet widely known. Whereas previously, the list of hereditary renal cancers in
      adults included von Hippel-Lindau disease and a rare form of chromosomal
      translocation, the list now includes the following syndromes: tuberous sclerosis,
      hereditary papillary renal cancer, Birt-Hogg-Dube syndrome, hereditary leiomyoma
      renal cell carcinoma, familial renal oncocytoma, hereditary nonpolyposis colon
      cancer, and medullary carcinoma of the kidney. In addition, a number of newly
      described but poorly understood syndromes are under investigation. Even at this
      early stage, it is clear that elucidation of the underlying genetic mutations
      that cause hereditary renal cancer syndromes will have profound implications for
      understanding the origins of nonhereditary renal tumors. These studies will
      likely culminate in a better understanding of the causes of renal cancer, its
      prevention, and, ultimately, its cure.

PMID- 12511667
TI  - Calcification in cystic renal masses: is it important in diagnosis?
AB  - PURPOSE: To determine whether the presence of calcifications in cystic renal
      masses is important in diagnosis and to suggest an approach to the management of
      calcified cystic renal masses. MATERIALS AND METHODS: Eighty-one cystic renal
      masses containing calcification in a wall or septum were evaluated by means of
      review of computed tomographic (CT) images (n = 81), follow-up CT images (n =
      28), and results of pathologic examination (n = 40) by the authors in consensus.
      Images were evaluated for lesion size, amount and morphology of calcification,
      and any association of calcification with soft-tissue structures. Lesions were
      categorized according to the Bosniak cyst classification system; the amount of
      calcification was determined with a subjective grading system. Progression of
      calcification was qualitatively determined with available follow-up CT scans.
      RESULTS: Twenty-one lesions were Bosniak category II (benign) and showed small
      amounts and thin strands of calcification. Nineteen lesions containing more
      extensive calcification but no enhancing tissue were category IIF. Follow-up CT
      results available for 16 of these lesions (average follow-up length, 5 years 8
      months) showed no substantial change. The three remaining lesions were proved
      benign at surgery. Twenty-five lesions were category III; surgical intervention
      was performed in 21 of these (benign, n = 12; malignant, n = 9). Sixteen lesions
      that contained obvious areas of enhancing soft tissue were category IV and proved
      malignant at surgery. CONCLUSION: Calcification in a cystic renal mass is not as
      important in diagnosis as is the presence of associated enhancing soft-tissue
      elements. This information should enable a reasonable approach to the management
      of calcium-containing renal cystic lesions.

PMID- 12511668
TI  - Living renal donors: optimizing the imaging strategy--decision- and cost
      effectiveness analysis.
AB  - PURPOSE: To determine the most cost-effective strategy for preoperative imaging
      performed in potential living renal donors. MATERIALS AND METHODS: In a decision
      analytic model, the societal cost-effectiveness of digital subtraction
      angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography,
      contrast material-enhanced spiral computed tomographic (CT) angiography, and
      combinations of these imaging techniques was evaluated. Outcome measures included
      lifetime cost, quality-adjusted life-years (QALYs), and incremental cost
      effectiveness ratios. A base-case analysis was performed with a 40-year-old
      female donor and a 40-year-old female recipient. RESULTS: For the donor, MR
      angiography (24.05 QALYs and 9,000 dollars) dominated all strategies except for
      MR angiography with CT angiography, which had an incremental ratio of 245,000
      dollars per QALY. For the recipient, DSA and DSA with MR angiography yielded
      similar results (10.46 QALYs and 179,000 dollars) and dominated all other
      strategies. When results for donor and recipient were combined, DSA dominated all
      other strategies (34.51 QALYs and 188,000 dollars). If DSA was associated with a
      99% specificity or less for detection of renal disease, MR angiography with CT
      angiography was superior (34.47 QALYs and 190,000 dollars). CONCLUSION: For
      preoperative imaging in a potential renal donor, DSA is the most cost-effective
      strategy if it has a specificity greater than 99% for detection of renal disease;
      otherwise, MR angiography with CT angiography is the most cost-effective
      strategy.

PMID- 12511669
TI  - Transportable versus fixed platform CT scanners: comparison of costs.
AB  - PURPOSE: To compare the aggregate hospital technical costs of a transportable
      computed tomographic (CT) scanner used to image patients in an intensive care
      unit with those of a fixed platform CT scanner in the radiology department.
      MATERIALS AND METHODS: Direct fixed costs (ie, machine and service contract
      costs) and direct variable costs (ie, personnel costs) were calculated. Indirect
      costs, including space costs and departmental overhead, were calculated. Total
      costs were calculated as the sum of indirect, direct fixed, and direct variable
      costs. Personnel costs were calculated from time-motion analyses involving 95
      patients who underwent brain CT with either a transportable (n = 51) or a fixed
      platform (n = 44) CT scanner. Costs per examination were calculated by using both
      low- and high-examination-volume models and compared with use of the Wilcoxon
      rank sum test. RESULTS: The total cost per examination for the transportable
      scanner ranged from 108.98 dollars to 167.20 dollars for the high- and low-volume
      models. Total cost per examination for the fixed platform scanner ranged from
      75.24 dollars to 112.39 dollars for the high- and low-volume models. For the
      transportable scanner, direct fixed, variable, and overhead costs were 87.05
      dollars, 70.73 dollars, and 9.42 dollars per examination, respectively, with the
      low-volume model. The corresponding costs for the fixed platform scanner were
      46.66 dollars, 55.69 dollars, and 10.04 dollars, respectively. CONCLUSION: The
      technical cost of using an in-hospital transportable CT scanner is higher than
      that of using a fixed platform scanner.

PMID- 12511670
TI  - The whirl sign.

PMID- 12511671
TI  - Evaluation of liver diffusion isotropy and characterization of focal hepatic
      lesions with two single-shot echo-planar MR imaging sequences: prospective study
      in 66 patients.
AB  - PURPOSE: To (a) evaluate liver diffusion isotropy, (b) compare two diffusion
      weighted magnetic resonance (MR) imaging sequences for the characterization of
      focal hepatic lesions by using two or four b values, and (c) determine an
      apparent diffusion coefficient (ADC) threshold value to differentiate benign from
      malignant lesions. MATERIALS AND METHODS: Sixty-six patients were examined with
      two single-shot echo-planar diffusion-weighted MR sequences. In the first
      sequence, liver diffusion isotropy was evaluated by using diffusion gradients in
      three directions with two b values. In the second sequence, a unidirectional
      diffusion gradient was used with four b values. ADCs were measured in 43 patients
      with 52 focal hepatic lesions more than 1 cm in diameter and in 23 patients with
      14 normal and nine cirrhotic livers and were compared by using nonparametric
      tests. RESULTS: Diffusion in the liver parenchyma was isotropic. ADCs of focal
      hepatic lesions were significantly different between sequences (P <.01). The mean
      (+/- SD) ADCs in the first sequence were 0.94 x 10(-3) mm(2)/sec +/- 0.60 for
      metastases, 1.33 x 10(-3) mm(2)/sec +/- 0.13 for HCCs, 1.75 x 10(-3) mm(2)/sec +/
      0.46 for benign hepatocellular lesions, 2.95 x 10(-3) mm(2)/sec +/- 0.67 for
      hemangiomas, and 3.63 x 10(-3) mm(2)/sec +/- 0.56 for cysts. There was a
      significant difference between benign (2.45 x 10(-3) mm(2)/sec +/- 0.96,
      isotropic value) and malignant (1.08 x 10(-3) mm(2)/sec +/- 0.50) lesions (P <.01
      for both sequences). CONCLUSION: Diffusion-weighted MR imaging can help
      differentiate benign from malignant hepatic lesions. The use of two b values in
      one direction could be sufficient for the design of MR sequences in the liver.

PMID- 12511672
TI  - Preoperative depiction of hepatocellular carcinoma: ferumoxides-enhanced MR
      imaging versus triple-phase helical CT.
AB  - PURPOSE: To compare ferumoxides-enhanced magnetic resonance (MR) imaging with
      triple-phase helical computed tomography (CT) for the preoperative depiction of
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy consecutive
      patients with a total of 79 HCC nodules underwent ferumoxides-enhanced MR imaging
      and triple-phase helical CT before surgery. The diagnosis of HCC was established
      by means of pathologic examination after surgical resection in all patients. MR
      images obtained with all sequences and triple-phase helical CT images were
      reviewed independently by three radiologists on a segment-by-segment basis.
      Accuracy for diagnosis of HCC was assessed by applying receiver operating
      characteristic (ROC) analysis to observations of 78 hepatic segments with at
      least one HCC nodule and 70 segments without HCC. RESULTS: The diagnostic
      accuracy of findings at ferumoxides-enhanced MR imaging (with mean area-under-the
      ROC-curve [A(z)] values for the three observers of 0.986, 0.979, and 0.980) was
      significantly higher (P <.001) than that of findings at triple-phase helical CT
      (with mean A(z) values for the three observers of 0.945, 0.948, and 0.964). The
      mean sensitivity of MR imaging (95%, 222 of 234 segments) was also significantly
      higher than that of triple-phase helical CT (88%, 205 of 234 segments) (P =.001,
      McNemar test). The mean specificity was 97% (261 of 270 segments) for MR imaging
      and 98% (264 of 270 segments) for CT, but this difference was not significant (P
      =.754, McNemar test). CONCLUSION: Ferumoxides-enhanced MR imaging is superior to
      triple-phase helical CT for the preoperative depiction of HCC.

PMID- 12511673
TI  - Segmental misty mesentery: analysis of CT features and primary causes.
AB  - PURPOSE: To review the computed tomographic (CT) features of segmental misty
      mesentery (SMM) in 29 patients and assess the primary causes of this CT finding.
      MATERIALS AND METHODS: The authors analyzed the medical records and CT features
      of SMM in 29 patients. CT images were evaluated for the site, thickness, and
      vascular changes of the involved mesentery; bowel wall changes; lymphadenopathy;
      and the fat ring sign. The primary cause of SMM in five patients was determined
      at histopathologic examination, that in three patients was determined at surgical
      observation of the mesentery, and that in nine patients was determined on the
      basis of follow-up CT and clinical data. The primary cause of SMM in 12 patients
      was unknown. RESULTS: Twenty-five of the 29 patients had various underlying
      diseases. Fourteen (48%) patients had a malignancy: 11 had intraabdominal cancer
      and three had extraabdominal cancer. Jejunal mesentery was more commonly involved
      than was ileal mesentery (P <.05). The mean thickness of the SMM was 4.0 cm.
      Mesenteric vessels were dilated in 27 patients (93%): 19 with venous dilatation
      and eight with either arterial dilatation only or both arterial and venous
      dilatation. At CT, seven (24%) patients had a thickened bowel wall; nine (31%)
      patients, lymphadenopathy; and two (7%) patients, the fat ring sign. The primary
      cause of SMM was edema in eight, malignant neoplasm in four, inflammation and/or
      fibrosis in five, and idiopathic in 12 patients. CONCLUSION: At CT, SMM appears
      as a result of malignant neoplasms, inflammation, or vascular disorders.

PMID- 12511674
TI  - Ovoid shape of the vermiform appendix: a criterion to exclude acute appendicitis-
      evaluation with US.
AB  - PURPOSE: To investigate whether the shape of the appendix in transverse section
      may be considered an ultrasonographic (US) criterion to exclude or confirm acute
      appendicitis. MATERIALS AND METHODS: The shapes of appendices of 100 control
      subjects, of 174 patients with clinical suspicion of acute appendicitis but
      without acute appendicitis, and of 108 patients with acute appendicitis were
      prospectively evaluated with US. Definite diagnoses in patients with clinical
      suspicion of acute appendicitis were established and confirmed either with
      surgery and histologic examination in 161 patients or with clinical follow-up in
      121 patients. Statistical measures such as sensitivity, specificity, positive and
      negative predictive values, and accuracy were assessed for the appendiceal shape
      as a diagnostic US criterion for acute appendicitis. RESULTS: An at least partly
      round appendix indicated acute appendicitis with a sensitivity of 100%;
      specificity of 37%; positive and negative predictive values of 50% and 100%,
      respectively; and accuracy of 61%. In 67 of 174 patients with clinical suspicion
      of acute appendicitis but without acute appendicitis, the partly ovoid
      appendiceal shape aided in the exclusion of acute appendicitis, since it
      indicated a normal appendix with a probability of 86%. In 65 of 174 patients with
      clinical suspicion of acute appendicitis but without acute appendicitis, the
      ovoid shape over the entire appendiceal length excluded acute appendicitis with
      confidence. CONCLUSION: The shape of the appendix in transverse section is a
      useful US criterion, since an ovoid shape over the entire appendiceal length
      reliably rules out acute appendicitis.

PMID- 12511675
TI  - US as a primary diagnostic tool in relation to negative appendectomy: six years
      experience.
AB  - PURPOSE: To evaluate the effect of ultrasonography (US) on the rate of
      appendectomy after false-positive diagnosis of acute appendicitis (negative
      appendectomy). MATERIALS AND METHODS: Data were analyzed in 736 pediatric
      patients (mean age, 13.2 years) who had undergone appendectomy between 1995 and
      2000. Histologic data were compared in patients who underwent US with those who
      did not undergo imaging prior to surgery. US was performed by a radiologist or a
      pediatric surgeon or both. RESULTS: A total of 643 (87.4%) of the 736 pediatric
      patients underwent preoperative US, and 93 (12.6%) of the 736 did not undergo
      preoperative US. Of the 736 patients, 97 (13.2%) underwent negative appendectomy.
      Thirty-four (36.6%) of the 93 patients who underwent appendectomy with no
      preoperative US and 63 (9.8%) of the 643 patients who underwent preoperative US
      underwent negative appendectomy. There was a significant association between US
      and positive appendectomy (P <.001). CONCLUSION: US in pediatric patients
      suspected of having appendicitis can significantly lower the negative
      appendectomy rate.

PMID- 12511676
TI  - Orthotopic liver transplants in children: change in hepatic venous Doppler wave
      pattern as an indicator of acute rejection.
AB  - PURPOSE: To determine whether a change in hepatic venous flow pattern can be seen
      during hepatic graft rejection and if it is reversible with treatment. MATERIALS
      AND METHODS: Thirty-nine children received 42 liver allografts during a 10-year
      span. Doppler ultrasonographic (US) recordings of hepatic venous wave patterns
      were reviewed. Nine children (ten grafts) with continuously monophasic flow were
      not included in the study. Changes from triphasic to monophasic flow were
      recorded and correlated with clinical findings in all 30 patients and biopsy
      findings in 25. Biopsy results were compared with US data recorded within 24
      hours of biopsy. Standard statistical tests were conducted to assess value of
      Doppler US in diagnosis of graft rejection. Significance was assessed with chi(2)
      statistics. RESULTS: Of 113 Doppler US recordings in 30 children, 74 showed an
      episode of change in flow from triphasic to monophasic in 27 patients; biopsy
      correlation existed for 39 episodes. Thirty-five episodes were due to acute graft
      rejection (true-positive results). Thirty-nine episodes were due to a variety of
      pathologic causes (determined with biopsy results for 12 and by clinical means
      for 27) (false-positive results). Thirty-six assessments were true-negative (US
      and biopsy results negative for rejection); three were false-negative. When US
      results were evaluated against clinical and biopsy data, analysis revealed that
      change to monophasic flow predicted rejection with sensitivity of 92% (35 of 38)
      and specificity of 48% (36 of 75). Negative predictive value of evidence of
      persistent triphasic flow was 92% (36 of 39). In the subgroup of US findings with
      biopsy correlation, specificity increased from 48% (36 of 75) to 75% (36 of 48).
      It was zero (0 of 27) for the group with clinical correlation only. CONCLUSION:
      Change of hepatic venous flow pattern from triphasic to monophasic is sensitive
      but nonspecific for detection of graft rejection. Evidence of persistent
      triphasic flow helps eliminate the possibility of graft rejection with a high
      negative predictive value.

PMID- 12511678
TI  - Case 54: Fournier gangrene.

PMID- 12511679
TI  - Occurrence of new vertebral body fracture after percutaneous vertebroplasty in
      patients with osteoporosis.
AB  - PURPOSE: To investigate the prevalence and findings of vertebral body compression
      fractures adjacent to those previously treated with percutaneous vertebroplasty.
      MATERIALS AND METHODS: The findings in 177 patients treated with percutaneous
      vertebroplasty for more than 2 years were reviewed retrospectively. The following
      parameters were reviewed: primary diagnosis, patient age and sex, date of
      treatment with vertebroplasty, vertebral level(s) treated, pedicular approach,
      and amount of polymethylmethacrylate injected per vertebral body. Patients with
      acute compression fractures secondary to osteoporosis were selected. RESULTS: Of
      177 patients treated with percutaneous vertebroplasty, 22 (12.4%) developed a
      total of 36 new vertebral body fractures following treatment. Of the 36 newly
      documented fractures, 24 (67%) involved vertebrae adjacent to the previously
      treated vertebral level(s), whereas 12 (33%) involved the collapse of nonadjacent
      vertebrae. In addition, 24 (67%) of the 36 new vertebral fractures occurred
      within 30 days after treatment of the initial fracture(s). CONCLUSION: A
      substantial number of patients with osteoporosis develop new fractures after
      undergoing percutaneous vertebroplasty; two-thirds of these new fractures occur
      in vertebrae adjacent to those previously treated.

PMID- 12511680
TI  - Osteoid osteoma: elevation of cardiac and respiratory rates at biopsy needle
      entry into tumor in 10 patients.
AB  - PURPOSE: To evaluate changes in cardiac and respiratory rates in a consecutive
      series of patients who underwent percutaneous treatment for lesions presumed to
      be osteoid osteoma in whom general anesthesia was established. MATERIALS AND
      METHODS: Changes in cardiac and respiratory rates were evaluated after
      establishment of stable general anesthesia in 14 patients who underwent needle
      biopsy and radio-frequency treatment. Cardiac and respiratory rates were recorded
      at penetration of skin, muscle, periosteum, cortex, and tumor. Treatment was
      performed before the biopsy report was available. RESULTS: Biopsy results
      revealed osteoid osteoma in 10 patients, chondroblastoma in one, and a herniation
      pit in one. Results in the two remaining patients were nondiagnostic and were
      excluded. Puncture of skin, muscle, and periosteum caused no detectable change.
      However, in the 10 patients with biopsy-proved osteoid osteoma, puncture of the
      tumor caused the mean cardiac rate to increase an average of 26 beats per minute
      (40%) to 91 (range, 62-114; P <.001) and the mean respiratory rate to increase an
      average of 12 breaths per minute (50%) to a mean of 37 (range, 25-52; P <.001).
      These changes occurred within seconds of tumor puncture and were often the first
      indication to the surgeon that the tumor had been entered. In the two patients
      with other diagnoses at biopsy, no such change was apparent. CONCLUSION: Mean
      cardiac and respiratory rates increase significantly at needle puncture of
      osteoid osteoma.

PMID- 12511681
TI  - First-pass MR imaging in the assessment of perfusion impairment in patients with
      hypertrophic cardiomyopathy and the Asp175Asn mutation of the alpha-tropomyosin
      gene.
AB  - PURPOSE: To assess first-pass magnetic resonance (MR) imaging in the evaluation
      of perfusion impairment in a genetically homogeneous population of patients with
      hypertrophic cardiomyopathy (HCM) and the Asp175Asn mutation of the alpha
      tropomyosin gene and to evaluate the association between hypertrophy and
      perfusion. MATERIALS AND METHODS: Rest-stress first-pass MR imaging with
      gadopentetate dimeglumine was performed in 17 patients with HCM and the Asp175Asn
      substitution in the alpha-tropomyosin gene and in five control subjects. Global
      and segmental first-pass reserve index (FPR) measurements were derived from
      signal intensity versus time curves. Left ventricular (LV) wall thickness and LV
      mass index were measured on cine MR images. The Mann-Whitney test was used to
      evaluate the difference in FPR between the patient group and the control group.
      The Spearman correlation was used to evaluate the association between LV
      hypertrophy and FPR. RESULTS: Global FPR was significantly lower in the patients
      with HCM than in the control subjects (1.12 +/- 0.35 vs 1.80 +/- 0.58, P =.015).
      In patients with HCM, maximal LV wall thickness and LV mass index correlated
      negatively with global FPR (r = -0.723, P =.001 and r = -0.598, P =.011,
      respectively). At the regional level, segmental FPR correlated inversely with LV
      wall thickness (r = -0.389; P <.001) in patients with HCM. CONCLUSION: First-pass
      MR imaging facilitates global and regional evaluation of perfusion impairment in
      patients with HCM. The severity of perfusion impairment is associated with the
      degree of LV hypertrophy.

PMID- 12511682
TI  - Acute myocardial infarction: myocardial viability assessment in patients early
      thereafter comparison of contrast-enhanced MR imaging with resting (201)Tl SPECT.
      Single photon emission computed tomography.
AB  - PURPOSE: To compare contrast material-enhanced magnetic resonance (MR) imaging
      with resting thallium 201 ((201)Tl) single photon emission computed tomography
      (SPECT) for predicting myocardial viability in patients early after acute
      myocardial infarction. MATERIALS AND METHODS: Inversion-recovery contrast
      enhanced MR images and resting (201)Tl SPECT images were obtained in 22 patients
      after acute myocardial infarction. The (201)Tl SPECT images were obtained 4.3
      days +/- 0.2 (standard error) after the onset of myocardial infarction. Contrast
      enhanced MR imaging was performed 7.9 days +/- 1.6 after (201)Tl SPECT.
      Transmural extent of hyperenhancement on contrast-enhanced MR images and regional
      (201)Tl activity were quantitatively analyzed with a 12-segment model. Regional
      wall thickening on follow-up cine MR images obtained 67 days +/- 17 after
      contrast-enhanced MR imaging was used as an index for myocardial viability.
      Statistical analyses were performed with the chi(2) and two-tailed Student t
      tests. RESULTS: Both contrast-enhanced MR and resting (201)Tl SPECT images showed
      significant correlations with regional wall thickening on follow-up cine MR
      images. The sensitivity, specificity, and accuracy of contrast-enhanced MR
      imaging in the prediction of viable myocardium were significantly higher than
      those of resting (201)Tl SPECT (98.0% vs 90.3%, P <.01; 75.0% vs 54.4%, P <.05;
      and 92.0% vs 81.1%, P <.001, respectively). CONCLUSION: Delayed contrast-enhanced
      MR imaging can help predict myocardial viability as seen on follow-up cine MR
      images after acute myocardial infarction, with significantly improved
      sensitivity, specificity, and accuracy in comparison with those of resting
      (201)Tl SPECT.

PMID- 12511683
TI  - Radiation exposure during cardiac CT: effective doses at multi-detector row CT
      and electron-beam CT.
AB  - PURPOSE: To measure the effective radiation doses delivered at electron-beam
      computed tomography (CT) and multi-detector row spiral CT of coronary arteries
      and to compare these doses with those delivered at catheter coronary angiography.
      MATERIALS AND METHODS: An anthropomorphic phantom equipped with 66
      thermoluminescent dosimeters was imaged at cardiac CT. Four protocols for
      unenhanced coronary artery calcium scoring were simulated: one with electron-beam
      CT and three with multi-detector row CT. Four similar protocols for coronary CT
      angiography were simulated. All multi-detector row spiral CT protocols were
      performed with retrospective electrocardiographic triggering. Biplane catheter
      coronary angiography also was simulated. Radiation doses to organs were measured,
      and effective doses were calculated according to guidelines published in
      International Commission on Radiological Protection Publication 60. RESULTS:
      Coronary artery calcium scoring with electron-beam CT yielded effective radiation
      doses of 1.0 and 1.3 mSv for male and female patients, respectively. The
      radiation doses at calcium scoring with multi-detector row CT were 1.5-5.2 mSv
      for male patients and 1.8-6.2 mSv for female patients. Electron-beam CT coronary
      angiography yielded effective doses of 1.5 and 2.0 mSv for male and female
      patients, respectively. The highest effective doses were delivered at multi
      detector row CT angiography: 6.7-10.9 mSv for male patients and 8.1-13.0 mSv for
      female patients. Catheter coronary angiography yielded effective doses of 2.1 and
      2.5 mSv for male and female patients, respectively. CONCLUSION: Higher radiation
      doses are delivered at multi-detector row cardiac CT compared with the doses
      delivered at electron-beam CT and catheter coronary angiography.

PMID- 12511684
TI  - Diagnostic accuracy of digital mammography in patients with dense breasts who
      underwent problem-solving mammography: effects of image processing and lesion
      type.
AB  - PURPOSE: To determine effects of lesion type (calcification vs mass) and image
      processing on radiologist's performance for area under the receiver operating
      characteristic curve (AUC), sensitivity, and specificity for detection of masses
      and calcifications with digital mammography in women with mammographically dense
      breasts. MATERIALS AND METHODS: This study included 201 women who underwent
      digital mammography at seven U.S. and Canadian medical centers. Three image
      processing algorithms were applied to the digital images, which were acquired
      with Fischer, General Electric, and Lorad digital mammography units. Eighteen
      readers participated in the reader study (six readers per algorithm). Baseline
      values for reader performance with screen-film mammograms were obtained through
      the additional interpretation of 179 screen-film mammograms. A repeated-measures
      analysis of covariance allowing unequal slopes was used in each of the nine
      analyses (AUC, sensitivity, and specificity for each of three machines).
      Bonferroni correction was used. RESULTS: Although lesion type did not affect the
      AUC or sensitivity for Fischer digital images, it did affect specificity (P
      =.0004). For the General Electric digital images, AUC, sensitivity, and
      specificity were not affected by lesion type. For Lorad digital images, the
      results strongly suggested that lesion type affected AUC and sensitivity (P
      <.0001). None of the three image-processing methods tested affected the AUC,
      sensitivity, or specificity for the Fischer, General Electric, or Lorad digital
      images. CONCLUSION: Findings in this study indicate that radiologist's
      interpretation accuracy in interpreting digital mammograms depends on lesion
      type. Interpretation accuracy was not influenced by the image-processing method.

PMID- 12511685
TI  - Infraspinatus muscle atrophy: implications?
AB  - PURPOSE: To evaluate associated findings in patients who exhibited atrophy of
      infraspinatus muscle at magnetic resonance (MR) examination of their shoulders to
      clarify implications of this abnormality. MATERIALS AND METHODS: With an
      electronic database search, cases of advanced infraspinatus muscle atrophy in
      patients who underwent MR imaging during a 1-year period for evaluation of
      shoulder pain or dysfunction were identified. The analysis was restricted to
      cases interpreted by one reader who applied a standardized method of reporting.
      Associated MR imaging findings in these cases were tabulated. RESULTS: Advanced
      infraspinatus muscle atrophy was encountered in 51 (4.3%) of 1,191 MR
      examinations of the shoulder. Tears of the infraspinatus tendon were present in
      only 27 (53%) of 51 cases. In 46 (90%) of 51 cases, a full-thickness tear was
      present in the anterior portion of the rotator cuff. In 10 (20%) of 51 cases with
      infraspinatus muscle atrophy, cuff muscle atrophy was confined to the
      infraspinatus muscle. Cuff muscle atrophy was isolated to the infraspinatus
      muscle in four (17%) of 24 cases in which atrophy of the infraspinatus muscle was
      present despite an intact tendon. In none of the 51 cases was there a mass in the
      suprascapular or sphenoglenoid notch. CONCLUSION: Infraspinatus muscle atrophy
      typically occurs with tendon tears in the anterior aspect of the rotator cuff.
      Concomitant atrophy in the supraspinatus muscle often is present, but
      infraspinatus muscle atrophy can occur in isolation, and this finding does not
      imply that the infraspinatus tendon is ruptured.

PMID- 12511686
TI  - Articular cartilage lesions of the glenohumeral joint: diagnostic effectiveness
      of MR arthrography and prevalence in patients with subacromial impingement
      syndrome.
AB  - PURPOSE: To determine the prevalence of articular cartilage lesions in patients
      with subacromial impingement syndrome and to assess the diagnostic effectiveness
      of magnetic resonance (MR) arthrography in detecting such cartilage
      abnormalities. MATERIALS AND METHODS: MR arthrographic images obtained in 52
      consecutive patients (mean age, 45.8 years; age range, 17-73 years; 26 male and
      26 female patients) were retrospectively evaluated for glenohumeral cartilage
      lesions. Two experienced musculoskeletal radiologists who were blinded to the
      arthroscopy report independently analyzed the articular cartilage. Humeral and
      glenoidal cartilage were assessed separately. The lesions were graded as either
      subtle or marked. Arthroscopic findings were the standard of reference.
      Sensitivity, specificity, accuracy, and interobserver agreement were calculated.
      RESULTS: At arthroscopy, humeral cartilage lesions were found in 15 patients
      (frequency, 29%). Four lesions were subtle, and 11 were marked. Cartilage lesions
      of the glenoid were less frequent (eight patients; frequency, 15%): Three were
      subtle, and five were marked. For reader 1 and reader 2, respectively,
      sensitivity of MR arthrography for humeral cartilage lesions was 53% and 100%,
      specificity was 87% and 51%, and accuracy was 77% and 65%; sensitivity for
      glenoidal cartilage lesions was 75% and 75%, specificity was 66% and 63%, and
      accuracy was 67% and 65%. Interobserver agreement for the grading of cartilage
      lesions with MR arthrography was fair (humeral lesions, kappa = 0.20; glenoidal
      lesions, kappa = 0.27). CONCLUSION: Glenohumeral cartilage lesions are found in
      up to one third of patients referred for MR arthrography for subacromial
      impingement syndrome. The performance of MR arthrography in the detection of
      glenohumeral cartilage lesions is moderate.

PMID- 12511687
TI  - Extrinsic carpal ligaments: normal MR arthrographic appearance in cadavers.
AB  - PURPOSE: To describe the normal magnetic resonance (MR) arthrographic anatomy of
      the major carpal ligaments (excluding scapholunate and lunotriquetral ligaments)
      and their osseous attachments by using standard imaging planes. MATERIALS AND
      METHODS: MR images of 22 wrists derived from fresh human cadaveric hands were
      obtained after tricompartmental arthrography. The MR arthrographic appearance of
      the carpal ligaments and their bone attachments were analyzed and correlated to
      those seen on anatomic sections. Two readers determined in consensus which was
      the best plane to observe the course and attachment sites for each ligament. They
      further analyzed the size and sites of attachment of these ligaments in two
      orthogonal planes chosen for optimal viewing. RESULTS: Each ligament was well
      seen as a hypointense linear structure with MR arthrography. The
      radioscaphocapitate, radiolunotriquetral, radioscapholunate, dorsal
      radiotriquetral, palmar scaphotriquetral, and dorsal scaphotriquetral ligaments
      were best evaluated in the transverse plane. The palmar and dorsal ulnotriquetral
      and ulnolunate ligaments were best visualized in the sagittal plane. The radial
      collateral ligament was best analyzed in the coronal plane. The attachment sites
      of all ligaments were best analyzed either in the transverse or sagittal planes.
      CONCLUSION: MR arthrography allows visualization of the carpal ligaments.
      Detailed knowledge of the normal appearance of these ligaments can serve as a
      baseline for future studies in which MR arthrography is used to characterize
      wrist instability.

PMID- 12511688
TI  - Screening for cerebral metastases with FDG PET in patients undergoing whole-body
      staging of non-central nervous system malignancy.
AB  - PURPOSE: To compare fluorine 18 fluorodeoxyglucose (FDG) positron emission
      tomography (PET) with the current standard, magnetic resonance (MR) imaging, to
      determine the sensitivity and specificity of FDG PET for detection of cerebral
      metastases and to determine the factors that may affect lesion conspicuity.
      MATERIALS AND METHODS: Forty patients underwent brain PET and contrast material
      enhanced brain MR imaging, with a maximum of 30 days between examinations. PET
      and MR images were each retrospectively reviewed by two independent readers who
      were blinded to the clinical history and results of the other technique. Presence
      of metastatic disease was recorded for each modality. Sensitivity and specificity
      of FDG PET were determined with MR imaging as the standard. Statistical analysis
      was performed with the Fisher exact test and the logistic regression model.
      RESULTS: Sixteen patients had cerebral metastases at MR imaging, and in 12 of
      these, PET scans were interpreted as showing metastatic disease (in four, scans
      were false-negative). Twenty-four patients had no cerebral metastases at MR
      imaging, and 20 of these had PET scans interpreted as normal (in four, scans were
      false-positive). For identification of patients with cerebral metastases, FDG PET
      had a sensitivity of 75% (12 of 16) and a specificity of 83% (20 of 24). Thirty
      eight metastatic lesions were seen at MR imaging; 23 (61%) of these were
      identified at PET. Size was a statistically significant factor that influenced
      lesion detection at PET (P <.001). CONCLUSION: Only 61% of metastatic lesions in
      the brain were identified at PET. In particular, detection of small lesions was
      difficult.

PMID- 12511689
TI  - Correlation of functional MR imaging activation data with simple reaction times.
AB  - PURPOSE: To determine the relationship between subject reaction times (RTs) and
      activation volume in the brain during visuomotor functional magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Twenty-four subjects performed a simple RT
      task during single-event functional MR imaging, and RTs were recorded. The six
      subjects with the fastest RTs were designated the fast RT group, and the six
      subjects with the slowest RTs were designated the slow RT group. The data were
      processed with noncorrected height threshold (P <.001) for individual comparisons
      and corrected height threshold (P <.05) for group comparisons (t tests). The
      activation volumes in both occipital lobes, the left sensorimotor cortex, and the
      supplemental motor cortices were compared for the two groups. RESULTS: The mean
      RT +/- SD was 342 msec +/- 20.15 for the fast RT group and 475 msec +/- 36.17 for
      the slow RT group (P <.0001). More voxels of activation were seen in the fast RT
      group than in the slow RT group in the occipital lobes, left sensorimotor
      cortices, and supplemental motor cortices on individual and group maps. This
      difference was statistically significant in the left sensorimotor (P =.03) and
      left visual (P =.05) cortices. In the right visual cortex, a trend toward more
      activation in the fast RT group was noted (P =.15). There was a negative
      correlation between RTs and activation volume in the left sensorimotor cortex (P
      =.048). CONCLUSION: There was a greater activation volume in motor and visual
      cortices in the fast RT group than in the slow RT group.

PMID- 12511690
TI  - Evidence of neuronal injury outside the medial temporal lobe in temporal lobe
      epilepsy: N-acetylaspartate concentration reductions detected with multisection
      proton MR spectroscopic imaging--initial experience.
AB  - PURPOSE: To determine whether magnetic resonance (MR) spectroscopic imaging
      reveals metabolic changes, especially decreased N-acetylaspartate (NAA)
      concentrations outside the medial temporal lobe in patients with mesial temporal
      lobe epilepsy (TLE), consistent with neuropathologic findings of extratemporal
      neuronal impairment. MATERIALS AND METHODS: Eleven patients with mesial TLE and
      13 control subjects were examined with multisection MR spectroscopic imaging.
      Three MR spectroscopic imaging sections were acquired. Thirteen brain regions in
      each hemisphere and the midbrain were analyzed in each patient, and the NAA to
      creatine-phosphocreatine (Cr) plus choline-containing compounds (Ch) (NAA/[Cr +
      Ch]) ratios were determined. In addition, hemispheric and whole-brain values were
      calculated and statistically analyzed. RESULTS: The NAA/(Cr + Ch) ratio in the
      ipsilateral hippocampus was significantly reduced, compared with that in the
      contralateral hippocampus (P <.002) and compared with that in control subjects (P
      <.03), confirming findings in previous studies. In patients, whole-brain NAA/(Cr
      + Ch) ratio outside the hippocampus was significantly lower than that in control
      subjects (P <.002). For the ipsilateral hemisphere in patients, NAA/(Cr + Ch)
      ratio was significantly lower than that in control subjects (P <.0002).
      Comparisons between individual brain regions revealed trends toward lower NAA/(Cr
      + Ch) ratios in many areas of the ipsilateral and, to a lesser extent, the
      contralateral hemisphere outside the hippocampus and temporal lobe, suggesting
      diffuse impairment. CONCLUSION: Results suggest that repeated seizure activity
      damages neurons outside of the seizure focus.

PMID- 12511691
TI  - Intracranial venous system: gadolinium-enhanced three-dimensional MR venography
      with auto-triggered elliptic centric-ordered sequence--initial experience.
AB  - PURPOSE: To evaluate gadolinium-enhanced three-dimensional auto-triggered
      elliptic centric-ordered (ATECO) magnetic resonance (MR) venography for imaging
      of the intracranial venous system. MATERIALS AND METHODS: ATECO MR venography was
      performed in 23 patients, eight of whom also underwent two-dimensional time-of
      flight (TOF) MR venography for imaging of the intracranial venous system.
      Seventeen predefined venous structures were evaluated on all venograms by two
      neuroradiologists. Visualization of venous structures was defined as completely
      visible (including clearly pathologic), partially visible, or not visible.
      Readers were also asked to compare the visibility of these predefined structures
      on ATECO and TOF MR venograms, where available. RESULTS: Of the 23 patients, six
      had dural venous sinus disease. Of the remaining 17 healthy patients, five
      underwent both ATECO and TOF MR venography and 12 underwent ATECO MR venography
      alone. On ATECO MR venograms obtained in the healthy patients, visibility of the
      17 predefined venous structures was complete in 92% (531 of 578) of evaluations.
      For the five normal TOF MR venograms, the rate of complete visibility of the same
      venous structures was 61% (104 of 170). The rate of complete visibility of the
      large dural venous sinuses was 99% for ATECO MR venograms and 75% for TOF MR
      venograms. CONCLUSION: ATECO MR venography provides high-quality images of the
      intracranial venous anatomy and was superior to TOF MR venography for consistent
      complete visibility of venous structures.

PMID- 12511692
TI  - Craniofacial duplication (diprosopus): CT, MR imaging, and MR angiography
      findings case report.
AB  - Diprosopus is one of the rarest malformations in humans. In addition to the
      facial structures, the cerebral frontal lobes were duplicated in this case. Three
      pairs of anterior cerebral arteries were detected, and the rostral parts of the
      superior sagittal sinus were duplicated. Computed tomography, magnetic resonance
      (MR) imaging, and MR angiography allowed study of the degree of duplicative
      changes in diprosopus, especially for planning cosmetic correction.

PMID- 12511693
TI  - Steady-state blood volume measurements in experimental tumors with different
      angiogenic burdens a study in mice.
AB  - PURPOSE: To experimentally validate the effectiveness of magnetic resonance (MR)
      imaging enhanced with long-circulating iron oxide for measurement of vascular
      volume fractions (VVFs) as indicators of angiogenesis in different experimental
      tumor models. MATERIALS AND METHODS: Tumors with differing degrees of
      angiogenesis-9L rodent gliosarcoma, DU4475 human mammary adenocarcinoma, HT1080
      human fibrosarcoma, and EOMA hemangioendothelioma--were implanted in nude mice.
      Tumoral VVFs were measured at submillimeter voxel resolutions by using 1.5-T MR
      imaging. A technetium-labeled intravascular radiotracer was injected into a
      subset of the animals to validate the MR imaging measurements. Microvessel
      density and vascular endothelial growth factor (VEGF) also were measured.
      Statistical analysis was performed with analysis of variance. RESULTS: High
      resolution multisection MR maps of tumor blood volume were obtained in all tumor
      models. Mean tumoral VVF differed significantly among the different tumors: 2.1%
      +/- 0.3 (standard error of mean) for 9L gliosarcoma, 3.1% +/- 0.4 for DU4475
      mammary adenocarcinoma, 5.5% +/- 0.8 for HT1080 fibrosarcoma, and 6.6% +/- 0.9
      for EOMA hemangioendothelioma (P <.01). There was a strong correlation between
      the MR imaging and radiotracer measurements. There was considerable intra- and
      intertumoral heterogeneity among the VVFs. MR imaging measurements were in
      accordance with conventional measurements of angiogenesis, such as microvessel
      density count and VEGF. CONCLUSION: Measurements of tumoral VVF at high
      resolution MR imaging with long-circulating iron oxide are feasible and correlate
      with angiogenic burden in experimental tumor models.

PMID- 12511694
TI  - Chest radiography: optimization of X-ray spectrum for cesium iodide-amorphous
      silicon flat-panel detector.
AB  - PURPOSE: To ascertain the optimum x-ray spectrum for chest radiography with a
      cesium iodide-amorphous silicon flat-panel detector. MATERIALS AND METHODS: End
      points for optimization included the ratio of tissue contrast to bone contrast
      and a figure of merit (FOM) equal to the square of the signal-to-noise ratio of
      tissue divided by incident exposure to the patient. Studies were conducted with
      both computer spectrum modeling and experimental measurement in narrow-beam and
      full-field exposure conditions for four tissue thicknesses (8-32 cm). Three
      parameters that affect spectra were considered: the atomic number (Z) of filter
      material (Z = 13, 26, 29, 42, 50, 56, 64, 74, and 82), kilovoltage (from 50 to
      150 kVp), and filter thickness (from 0.25 to 2.00 half-value layer [HVL]).
      RESULTS: Computer modeling and narrow-beam experimental data showed similar
      trends for the full range of parameters evaluated. Spectrum model results showed
      that copper filtration at 120 kVp or more was optimum for FOM. The ratio of
      contrasts showed a trend to be higher with higher kilovoltage and only a minor
      variation with filter material. Full-field experimental results, which reflect
      the added contribution of x-ray scatter, differed in magnitude but not trends
      from the narrow-beam data in all cases except the ratio of contrasts in the
      mediastinum. CONCLUSION: The best performance overall, including both FOM and
      ratio of contrasts, was at 120 kVp with 1-HVL copper filtration (0.2 mm). With
      this beam spectrum and an increase in tube output (ie, milliampere seconds) of
      about 50%, a chest radiograph can be obtained with image quality approximately
      equal to that with a conventional spectrum but with about 25% less patient
      exposure.

PMID- 12511695
TI  - Detection of pulmonary metastases with multi-detector row CT scans of 5-mm
      nominal section thickness: autopsy lung study.
AB  - PURPOSE: To determine the effect of changing pitch and collimation on depiction
      of pulmonary metastases on scans of 5-mm section thickness obtained with multi
      detector row computed tomography (CT) compared with those obtained with single
      detector row CT. MATERIALS AND METHODS: In five autopsy lungs, 1,013 metastatic
      0.5-30.0-mm nodules were detected at helical CT with 1-mm collimation and
      histopathologically diagnosed as metastases. Each nodule was numbered, and its
      localization was recorded as the standard for subsequent studies. Four types of
      scans of 5-mm section thickness were obtained with multi-detector row CT and four
      sets of helical pitch and table speed, respectively, as follows: set A, 3:1 and
      7.5 mm per rotation; set B, 6:1 and 15 mm per rotation; set C, 6:1 and 30 mm per
      rotation; set D, conventional and 5-mm interval. Conventional helical CT scans
      (set E) were obtained with 5-mm collimation at single-detector row CT. Two
      independent observers evaluated the five sets of CT scans. RESULTS: Acquisition
      times for sets A-D, respectively, were 1.9, 3.8, 7.5, and 1.5 times faster than
      they were for set E. The mean numbers of detected nodules were 671 (66%) in set
      A, 661 (65%) in set B, 678 (67%) in set C, 654 (65%) in set D, and 656 (65%) in
      set E; there was no significant difference in the number of detected nodules
      among the five sets (P =.997, McNemar test and Bonferroni equation). CONCLUSION:
      Regardless of varying pitch or detector collimation, multi- and single-detector
      row CT scans obtained with 5-mm section thickness have almost the same ability to
      depict pulmonary metastases and are equivalent.

PMID- 12511696
TI  - Missed non-small cell lung cancer: radiographic findings of potentially
      resectable lesions evident only in retrospect.
AB  - PURPOSE: To assess for change in the 1990s in the failure of detection at chest
      radiography of potentially resectable non-small cell lung cancer (NSCLC) lesions
      compared with experience in the previous decade. MATERIALS AND METHODS: From 1993
      to 2001, an observational cohort was identified that consisted of 40 instances of
      NSCLC evident retrospectively at chest radiography but undetected by a
      radiologist at a time when the cancer was potentially resectable for cure. Sizes
      and locations of the tumors were assessed. Pearson chi(2) testing was performed
      to compare the sex distribution of lung cancer in the present series with
      population data for the sex distribution of lung cancer in the United States
      during the present study. RESULTS: Twenty-five (62%) undetected NSCLCs were in
      men and 15 (38%) were in women, yielding a ratio not significantly different from
      that for the sex distribution of NSCLC according to national data (chi(2) = 0.22,
      P =.64). Median patient age was 62 years (range, 37-87 years). Median diameter of
      the missed cancers was 1.9 cm. Missed cancers were most commonly located in the
      upper lobes (right, 45%; left, 28%; total, 72%), especially in the apical and
      posterior segments/subsegments (60% of all the missed cancers). A clavicle
      obscured 22% of the missed cancers. Eighty-five percent of the missed cancers
      were in peripheral locations. CONCLUSION: Potentially resectable NSCLC lesions
      missed at chest radiography were characterized by predominantly peripheral (85%)
      and upper lobe (72%) locations and by apical and posterior segmental/subsegmental
      locations in an upper lobe (60%). Distribution by sex of the missed cancers was
      comparable to national data for NSCLC. The missed cancers had a median diameter
      of 1.9 cm.

PMID- 12511697
TI  - Lung morphology: fast MR imaging assessment with a volumetric interpolated breath
      hold technique: initial experience with patients.
AB  - PURPOSE: To prospectively evaluate the clinical feasibility of magnetic resonance
      (MR) imaging of the lungs with fast volumetric interpolated three-dimensional
      (3D) gradient-recalled-echo (GRE) sequences and to compare this examination with
      standard computed tomography (CT) in patients with lung abnormalities. MATERIALS
      AND METHODS: Twenty-five patients with different lung abnormalities were examined
      with 3D GRE MR imaging. The small pulmonary nodules in seven, TNM stage of large
      intrapulmonary tumors in eight, and benign bronchial disease in five patients
      were evaluated. MR imaging-based diagnoses were compared with diagnoses made at
      CT and at discharge from the hospital. Contingency tables and the McNemar test
      were used to evaluate the significance of differences between MR imaging- and CT
      based diagnoses. RESULTS: The MR imaging- and CT-based diagnoses were identical
      in 24 of 25 patients. In the remaining patient, clinical findings confirmed the
      accuracy of the MR imaging finding of pleural empyema. Ten of 15 solid pulmonary
      nodules smaller than 10 mm in diameter were detected at MR imaging (P >.1). Tumor
      stages at MR imaging and CT were identical, but lymph node stages at the two
      examinations differed in two of eight patients owing to overestimation of lymph
      node size at MR imaging (P >.2). In the five patients with bronchiectasis, MR
      imaging depicted 26 of 33 affected lung segments; differences between MR imaging
      and CT findings of bronchial dilatation (P >.05) and bronchial wall thickening (P
      >.2) were not significant. Peribronchial fibrosis was overestimated at MR imaging
      owing to image artifacts (P <.05). CONCLUSION: Study results confirmed the
      feasibility of fast breath-hold 3D GRE MR imaging of the lung.

PMID- 12511698
TI  - Artificial thorax for MR imaging studies in porcine heart-lung preparations.
AB  - A double-walled magnetic resonance (MR) imaging-compatible container with a
      flexible diaphragm was designed to hold freshly excised porcine heart-lung
      preparations. The saline contents simulate MR signal of an actual chest wall.
      Continuous evacuation keeps the lung inflated. A variety of experiments with
      different imaging modalities, including angiography, under close to in vivo
      conditions are feasible. Access to bronchial system and lung vessels allows for
      various studies.

PMID- 12511699
TI  - Lung micronodules: automated method for detection at thin-section CT--initial
      experience.
AB  - An automated system was developed for detecting lung micronodules on thin-section
      computed tomographic images and was applied to data from 15 subjects with 77 lung
      nodules. The automated system, without user interaction, achieved a sensitivity
      of 100% for nodules (>3 mm in diameter) and 70% for micronodules (<or=3 mm). With
      the same images, a radiologist detected nodules and micronodules with
      sensitivities of 91% and 51%, respectively, without system input. With assistance
      from the automated system, these sensitivities increased to 95% and 74%,
      respectively. Preliminary results indicate that the automated system considerably
      improved the radiologist's performance in micronodule detection.

PMID- 12511700
TI  - Coronary artery: quantitative evaluation of normal diameter determined with
      electron-beam CT compared with cine coronary angiography initial experience.
AB  - Eight male heart transplant recipients underwent contrast material-enhanced
      electron-beam computed tomographic angiography. Coronary artery diameters
      measured with fixed thresholds and adaptive line density profile (LDP) methods
      were calculated relative to findings at quantitative coronary angiography.
      Variation with fixed-threshold methods was significantly greater than that with
      LDP methods because of variations in vessel enhancement. Thus, more accurate
      measurements of vessel diameter were obtained with LDP methods.

PMID- 12511701
TI  - Two- and three-dimensional MR coronary angiography with intraarterial injections
      of contrast agent in dogs: a feasibility study.
AB  - Magnetic resonance (MR) images of coronary arteries were acquired with an
      inversion recovery-prepared technique after intraarterial injection of contrast
      material in five dogs. Real-time two-dimensional projection images were obtained
      with a temporal resolution of 3 frames per second. Three-dimensional
      electrocardiographically triggered high-spatial-resolution images were obtained
      with a fraction of the contrast agent required for intravenous injections.
      Background tissues were adequately suppressed in all images. On the basis of this
      experimental data, the optimal contrast agent concentration for two-dimensional
      real-time projection imaging was 6%. This preliminary work shows that contrast
      material-enhanced MR angiography with intraarterial injections is feasible with
      the proposed techniques.

PMID- 12511702
TI  - Tetralogy of Fallot: postoperative delayed recovery of left ventricular stroke
      volume after physical exercise assessment with fast MR imaging.
AB  - In six asymptomatic patients with corrected tetralogy of Fallot and nine healthy
      control subjects, the authors assessed left ventricular (LV) function during
      recovery from supine bicycle exercise by performing fast magnetic resonance (MR)
      flow mapping in the ascending aorta. Abnormal recovery of LV function after
      exercise was observed in the patients. MR flow mapping allows assessment of
      cardiac recovery after exercise.

PMID- 12511703
TI  - MR imaging in the assessment of staging of neuroblastoma.

PMID- 12511704
TI  - Should we replace bone scintigraphy plus CT with MR imaging for staging of
      neuroblastoma?

PMID- 12511705
TI  - H MR spectroscopy in the evaluation of the severity of chronic liver disease.

PMID- 12511706
TI  - CT characterization of adrenal masses.

PMID- 12511707
TI  - Usefulness of multiplanar reconstructions in evaluation of carotid CT
      angiography.

PMID- 12511710
TI  - British Thoracic Society guidelines on respiratory aspects of fitness for diving.

PMID- 12511712
TI  - Comparison of atopic cough with cough variant asthma: is atopic cough a precursor
      of asthma?
AB  - BACKGROUND: We have described a group of patients who present with isolated
      chronic bronchodilator resistant non-productive cough with an atopic
      constitution, eosinophilic tracheobronchitis, and airway cough receptor
      hypersensitivity without bronchial hyperresponsiveness, which we have termed
      "atopic cough". Although cough variant asthma (in which the cough responds to
      bronchodilators) is recognised as a precursor of typical asthma, it is not known
      whether atopic cough is also a precursor of asthma. METHODS: Eighty two patients
      with atopic cough were retrospectively examined for onset of typical asthma and
      compared with 55 patients with cough variant asthma (20 untreated patients and 35
      treated with long term inhaled beclomethasone dipropionate (BDP), 218-467 micro
      g/day). The median follow up period for patients with atopic cough and cough
      variant asthma was 4.8 (1-11.5) years and 3.7 (1-12.4) years, respectively.
      RESULTS: Onset of typical asthma occurred in only one of the patients with atopic
      cough. In patients with cough variant asthma, typical asthma developed in two of
      35 patients taking BDP and six of 20 untreated patients (difference 24.3%, 95% CI
      2.8 to 45.8, p<0.02). CONCLUSIONS: These findings suggest that cough variant
      asthma is a precursor of typical asthma but that atopic cough is not. Treatment
      with inhaled steroids may prevent the transformation of cough variant asthma into
      typical asthma.

PMID- 12511713
TI  - Cough receptor sensitivity to capsaicin does not change after allergen
      bronchoprovocation in allergic asthma.
AB  - BACKGROUND: The relationship between cough receptor sensitivity and eosinophilic
      inflammation of the airway in patients with asthma remains unclear. METHODS:
      Eighteen patients with asthma sensitised to house dust mite (HDM) were enrolled
      in a randomised parallel group study. Patients with asthma whose main symptom was
      cough were not enrolled in the study. Half the patients were randomly assigned to
      inhale saline and the other half to inhale HDM allergen. Cough receptor
      sensitivity to capsaicin, airway responsiveness to histamine, and sputum
      eosinophils analysed with hypertonic saline inhalation were investigated before
      and 24 hours after saline or HDM allergen bronchoprovocation. RESULTS: Patients
      inhaling saline showed no significant changes in sputum eosinophils (from 7.87%
      (95% confidence interval (CI) 5.08 to 12.19) to 8.60% (95% CI 3.03 to 14.18);
      p=0.97), airway responsiveness to histamine (from 726.68 micro g/ml (95% CI
      251.90 to 2096.36) to 773.01 micro g/ml (95% CI 251.36 to 2377.23); p=0.96), or
      capsaicin sensitivity (from 7.23 micro M (95% CI 2.45 to 21.31) to 7.24 micro M
      (95% CI 2.46 to 21.31); p=0.96). Early asthmatic response was induced in all
      patients, and late asthmatic response was observed in six of nine patients
      inhaling HDM allergen. Although there were significant increases in sputum
      eosinophils (from 9.83% (95% CI 6.78 to 14.27) to 21.00% (95% CI 13.85 to 28.15);
      p<0.01) and airway responsiveness to histamine (from 784.16 micro g/ml (95% CI
      318.24 to 1932.24) to 377.81 micro g/ml (95% CI 118.43 to 1205.24); p<0.05) 24
      hours after HDM allergen inhalation compared with baseline levels, capsaicin
      sensitivity did not change significantly (from 5.75 micro M (95% CI 1.91 to
      17.30) to 6.20 micro M (95% CI 2.21 to 17.38); p=0.77). CONCLUSIONS: These
      findings suggest that cough receptor sensitivity to capsaicin is not associated
      with eosinophilic inflammation of the airway in patients with allergic asthma
      whose main symptoms are wheezing and dyspnoea but not cough.

PMID- 12511714
TI  - Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of
      activated intraepithelial T cells (CD69+ CD103+).
AB  - BACKGROUND: T cells of intraepithelial phenotype have previously been detected in
      bronchoalveolar lavage (BAL) fluid in a range of lung diseases; these cells
      express the adhesion molecule alpha(E)beta(7) integrin, CD103, the ligand for
      epithelial cell E-cadherin. In subjects with asthma CD4+ lymphocytes are the
      predominant T cell subtype found in bronchial biopsy specimens and in BAL fluid,
      whereas CD8+ lymphocytes have been shown to predominate in subjects with chronic
      obstructive pulmonary disease (COPD). The aim of this study was to analyse the
      expression of CD103, activation markers (CD25 and CD69), and chemokine receptors
      (CXCR3, CCR5 and CCR3) on CD4+ and CD8+ lymphocytes from sputum and peripheral
      blood of subjects with asthma, COPD, and healthy controls. METHODS: T cell
      surface markers were assessed by immunofluorescence labelling and flow cytometry
      of gated lymphocytes among CD45+ leucocytes in sputum cell suspensions. RESULTS:
      Sputum lymphocytes expressed higher levels of CD103 and CD69 than blood
      lymphocytes in all subject groups, with CD103 expressed at higher levels on CD8+
      than on CD4+ cells. There were no detectable differences in numbers of CD4+ and
      CD8+ T cells between subjects with asthma, COPD and controls. The percentage of
      sputum lymphocytes expressing CXCR3 was lower in subjects with asthma or COPD
      than in healthy controls; CCR3 was not detectable on sputum or blood lymphocytes.
      CONCLUSIONS: Sputum T lymphocytes are predominantly of activated intraepithelial
      phenotype (CD103+ CD69+), and normal numbers of CD4+ and CD8+ T cell populations
      are found in the sputum of patients with asthma and COPD.

PMID- 12511716
TI  - Self-management of asthma in general practice, asthma control and quality of
      life: a randomised controlled trial.
AB  - BACKGROUND: A study was undertaken to determine the effectiveness of asthma self
      management in general practice. METHODS: Nineteen general practices were randomly
      allocated to usual care (UC) or self-management (SM). Asthma patients were
      included after confirmation of the GP diagnosis. Follow up was 2 years. Patients
      kept diary cards and visited the lung function laboratory every 6 months.
      Outcomes were number of successfully treated weeks, limited activity days, asthma
      specific quality of life, forced expiratory volume in 1 second (FEV(1)), FEV(1)
      reversibility, concentration of histamine provoking a fall in FEV(1) of 20% or
      more (PC(20) histamine), and amount of inhaled steroids. RESULTS: A total of 214
      patients were included in the study (104 UC/110 SM; one third of the total asthma
      population in general practice); 62% were female. The mean percentage of
      successfully treated weeks per patient in the UC group was 72% (74/103 weeks)
      compared with 78% (81/105 weeks) in the SM group (p=0.003). The mean number of
      limited activity days was 1.2 (95% CI 0.5 to 1.9) in the SM group and 3.9 (95% CI
      2.5 to 5.4) in the UC group. The estimated increase in asthma quality of life
      score was 0.10 points per visit in the UC group and 0.21 points per visit in the
      SM group (p=0.055). FEV(1), FEV(1) reversibility, and PC(20) histamine did not
      change. There was a saving of 217 puffs of inhaled steroid per patient in favour
      of the SM group (p<0.05). CONCLUSION: Self-management lowers the burden of
      illness as perceived by patients with asthma and is at least as effective as the
      treatment usually provided in Dutch primary care. Self-management is a safe basis
      for intermittent treatment with inhaled corticosteroids.

PMID- 12511718
TI  - Respiratory viruses in exacerbations of chronic obstructive pulmonary disease
      requiring hospitalisation: a case-control study.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AE
      COPD) are a common cause of hospital admission. Many exacerbations are believed
      to be due to upper and/or lower respiratory tract viral infections, but the
      incidence of these infections in patients with COPD is still undetermined.
      METHODS: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3,
      and picornaviruses were detected by nested reverse transcription polymerase chain
      reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens
      (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE
      COPD and 42 patients with stable COPD admitted for other medical reasons were
      studied. RESULTS: Respiratory viruses were found more often in sputum and nasal
      lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD
      (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%),
      influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed
      separately, this difference was seen in induced sputum (exacerbation 40/85 (47%)
      v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage
      (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD,
      fever was more frequent in those in whom viruses were detected (12/48, 25%) than
      in those in whom viruses were not detected (2/37, 5%, p=0.03). CONCLUSION: Viral
      respiratory pathogens are found more often in respiratory specimens of
      hospitalised patients with AE-COPD than in control patients. Induced sputum
      detects respiratory viruses more frequently than nasal lavage in these patients.
      These data indicate that nasal lavage probably has no additional diagnostic value
      to induced sputum in cross-sectional studies on hospitalised patients with AE
      COPD and that the role of viral infection in these patients is still
      underestimated.

PMID- 12511719
TI  - Inhaled short acting beta agonist use in COPD and the risk of acute myocardial
      infarction.
AB  - BACKGROUND: A recent study found that short acting beta agonists used in the
      treatment of asthma and chronic obstructive pulmonary disease (COPD) may increase
      the risk of acute myocardial infarction. We investigated this hypothesis in
      patients with COPD already at high risk of cardiac disease. METHODS: The
      Saskatchewan Health Services databases were used to form a population based
      cohort of all patients newly diagnosed with COPD over the age of 55 years
      identified between 1980 and 1997. All subjects were followed up until 1999,
      death, or the first occurrence of acute myocardial infarction. Those with a first
      acute myocardial infarction, fatal or non-fatal, were matched on calendar time
      and age with cohort members. RESULTS: The cohort consisted of 12 090 subjects
      including 1127 cases with fatal or non-fatal acute myocardial infarction. The
      adjusted rate ratio for current use of inhaled beta agonists was 1.12 (95%
      confidence interval (CI) 0.95 to 1.33), and for first time use it was 1.02 (95%
      CI 0.52 to 2.00). There was also no significant increase in risk when the
      analysis was restricted to subjects with cardiac risk factors such as
      hypertension and diabetes, or to subjects not having been prescribed beta blocker
      medications. CONCLUSION: Short acting inhaled beta agonist use among patients
      with COPD does not appear to increase the risk of fatal or non-fatal acute
      myocardial infarction.

PMID- 12511720
TI  - Prospective use of serial questionnaires to evaluate the therapeutic efficacy of
      18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung
      cancer.
AB  - BACKGROUND: A study was undertaken to study the effect of (18)F
      fluorodeoxyglucose (FDG) positron emission tomography (PET) on the diagnosis and
      management of clinically problematic patients with suspected non-small cell lung
      cancer (NSCLC). METHODS: A prospective before-after study was performed in a
      cohort of all 164 patients (university/community settings) referred for PET
      between August 1997 and July 1999. PET was restricted to cases where non-invasive
      tests had failed to solve clinical problems. The impact on diagnostic
      understanding and management was assessed using questionnaires (intended
      treatment without PET, actual treatment choice after PET, post hoc clinical
      assessment). RESULTS: Diagnostic problems especially pertained to unclear
      radiological findings (n=112; 63%), mediastinal staging (n=36; 20%), and distant
      staging issues (n=16; 9%). PET findings were validated by reviewing medical
      records. PET had a positive influence on diagnostic understanding in 84%.
      Improved diagnostic understanding solely based on PET was reported in 26%.
      According to referring physicians, PET resulted in beneficial change of treatment
      in 50%. Cancelled surgery was the most frequent change in treatment after PET
      (35%). CONCLUSION: FDG PET applied as "add on" technology in patients with these
      clinical problems appears to be a clinically useful tool, directly improving
      treatment choice in 25% of patients. The value of increased confidence induced by
      PET scanning requires further evaluation.

PMID- 12511721
TI  - High serum concentrations of surfactant protein A in usual interstitial pneumonia
      compared with non-specific interstitial pneumonia.
AB  - BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by
      surgical lung biopsy is important for clinical decision making. There is a need,
      however, to use serum markers for differentiating usual interstitial pneumonia
      (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX),
      and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation
      of activity of ILD. We have investigated the usefulness of these proteins as
      markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of
      the above five markers were measured in 57 patients with various forms of ILD (19
      with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with
      bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis),
      eight patients with the control disease (diffuse panbronchiolitis (DPB)), and
      nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in
      patients with UIP and NSIP were significantly higher than in healthy volunteers.
      In particular, the serum levels of SP-A in patients with UIP were significantly
      higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95%
      confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients
      with UIP were significantly lower than in patients with NSIP (p=0.01, mean
      difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum
      SP-A levels may be clinically useful as a biomarker to differentiate between UIP
      and NSIP.

PMID- 12511723
TI  - Can diaphragmatic contractility be assessed by airway twitch pressure in
      mechanically ventilated patients?
AB  - BACKGROUND: In critically ill patients inspiratory muscle function may be
      assessed by measurements of maximal inspiratory airway pressure and the response
      of twitch transdiaphragmatic pressure (Pdi tw) to bilateral phrenic nerve
      stimulation. The first is limited by its total dependence on patient cooperation.
      Although the second approach is independent of patient volition, it is
      impractical because it requires oesophageal and gastric balloons. Because airway
      pressure is easily and non-invasively recorded in patients with artificial
      airways, we hypothesised that twitch airway pressure (Paw tw) reliably predicts
      Pdi tw and twitch oesophageal pressure (Poes tw) in mechanically ventilated
      patients. METHODS: Thirteen mechanically ventilated patients recovering from an
      episode of acute respiratory failure received phrenic nerve stimulation at end
      exhalation. The rapid occlusion technique was used to record respiratory system
      mechanics. RESULTS: Stimulations were well tolerated. Mean (SE) Paw tw at end
      exhalation was -8.2 (1.2) cm H(2)O and Poes tw and Pdi tw were -7.3 (1.1) and
      10.4 (1.8) cm H(2)O, respectively. Stimulations produced a good correlation
      between Paw tw and Pdi tw (p<0.001), although the limits of agreement were wide.
      The results were similar for Poes tw. No relationship was found between the Paw
      tw/Poes tw ratio and respiratory system compliance or airway resistance. Paw tw
      reproducibility was excellent (mean coefficient of variation 6%, range 3-9%).
      CONCLUSIONS: Despite a good correlation between Paw tw and Poes tw, Paw tw did
      not reliably predict Poes tw or Pdi tw in mechanically ventilated patients.
      Nevertheless, the excellent reproducibility of Paw tw suggests that it may be a
      useful means of monitoring inspiratory muscle contractility in the routine care
      of mechanically ventilated patients.

PMID- 12511724
TI  - Reduced interferon-gamma release in patients recovered from Legionnaires'
      disease.
AB  - BACKGROUND: Legionella pneumophila, a Gram negative intracellular pathogen,
      causes Legionnaires' disease (LD). Interferon (IFN)-gamma is important for host
      defence against L pneumophila so reduced IFN-gamma production capacity and/or
      responsiveness might render humans more susceptible to infection with L
      pneumophila. METHODS: Seventy seven patients who suffered from LD after a point
      source outbreak one year earlier participated in the study. Whole blood was
      incubated with non-specific stimuli (lipopolysaccharide (LPS) or interleukin (IL)
      12) or specific stimuli (viable or heat killed L pneumophila) to evaluate IFN
      gamma production, and with IFN-gamma to evaluate IFN-gamma responsiveness.
      Expression of complement receptor 3 on monocytes was determined by flow
      cytometry. Thirty seven companions who were also exposed but had not developed LD
      served as controls. RESULTS: Patients released less IFN-gamma than controls in
      response to stimulation with LPS (mean (SE) 393 (58) pg/ml v 914 (178) pg/ml;
      p=0.001) and IL-12 (96 (14) pg/ml v 177 (41) pg/ml; p=0.058). IFN-gamma
      responsiveness, measured by release of IFN-gamma inducible protein (IP)-10,
      tumour necrosis factor alpha, IL-12 production capacity, and monocyte expression
      of complement receptor 3, did not differ between patients and controls. IFN-gamma
      release after stimulation with LPS and IP-10 release after stimulation with IFN
      gamma were weakly associated with severity of LD in the former patient group
      (rho=-0.3, p=0.011 and rho=-0.3, p=0.037, respectively). CONCLUSION: These
      results suggest that impaired IFN-gamma production may contribute to
      susceptibility to L pneumophila infection.

PMID- 12511725
TI  - Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels
      in bronchiectatic patients with and without primary ciliary dyskinesia.
AB  - BACKGROUND: Primary ciliary dyskinesia (PCD) is associated with chronic airway
      inflammation resulting in bronchiectasis. METHODS: The levels of exhaled nitric
      oxide (eNO), carbon monoxide (eCO) and nasal NO (nNO) from bronchiectatic
      patients with PCD (n=14) were compared with those from patients with non-PCD
      bronchiectasis without (n=31) and with cystic fibrosis (CF) (n=20) and from
      normal subjects (n=37) to assess the clinical usefulness of these measurements in
      discriminating between PCD and other causes of bronchiectasis. RESULTS: Exhaled
      NO levels were lower in patients with PCD than in patients with non-PCD non-CF
      bronchiectasis or healthy subjects (median (range) 2.1 (1.3-3.5) ppb v 8.7 (4.5
      26.0) ppb, p<0.001; 6.7 (2.6-11.9) ppb, p<0.001, respectively) but not lower than
      bronchiectatic patients with CF (3.0 (1.5-7.5) ppb, p>0.05). Nasal levels of nNO
      were significantly lower in PCD patients than in any other subjects (PCD: 54.5
      (5.0-269) ppb, non-PCD bronchiectasis without CF: 680 (310-1000) ppb, non-PCD
      bronchiectasis with CF: 343 (30-997) ppb, control: 663 (322-1343) ppb). In
      contrast, eCO levels were higher in all patient groups than in control subjects
      (PCD: 4.5 (3.0-24.0) ppm, p<0.01, other bronchiectasis without CF: 5.0 (3.0-15.0)
      ppm, p<0.001; CF: 5.3 (2.0-23.0) ppm, p<0.001 v 3.0 (0.5-5.0) ppm). Low values in
      both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD
      patients from other bronchiectatic patients with a specificity of 98% and a
      positive predictive value of 92%. CONCLUSION: The simultaneous measurement of eNO
      and nNO is a useful screening tool for PCD.

PMID- 12511727
TI  - Chronic obstructive pulmonary disease . 6: The aetiology of exacerbations of
      chronic obstructive pulmonary disease.
AB  - Exacerbations of COPD are thought to be caused by interactions between host
      factors, bacteria, viruses, and changes in air quality to produce increased
      inflammation in the lower airway. The evidence for this and the potential
      mechanisms by which they result in the characteristic symptoms of exacerbations
      is reviewed. A better understanding of the causes and processes is needed for the
      appropriate use of existing treatments and the development of new ones. Future
      studies need to define populations clearly, stratify for known confounding
      factors, and should aim to identify clinical correlates so that clinical practice
      can be modified appropriately.

PMID- 12511729
TI  - Catamenial haemoptysis and clomiphene citrate therapy.
AB  - Case reports of catamenial haemoptysis are uncommon. We report the first case of
      thoracic endometriosis associated with clomiphene citrate therapy and previously
      unpublished endobronchial and angiographic findings.

PMID- 12511728
TI  - The pulmonary physician in critical care . 12: Acute severe asthma in the
      intensive care unit.
AB  - Most deaths from acute asthma occur outside hospital, but the at-risk patient may
      be recognised on the basis of prior ICU admission and asthma medication history.
      Patients who fail to improve significantly in the emergency department should be
      admitted to an HDU or ICU for observation, monitoring, and treatment. Hypoxia,
      dehydration, acidosis, and hypokalaemia render the severe acute asthmatic patient
      vulnerable to cardiac dysrrhythmia and cardiorespiratory arrest. Mechanical
      ventilation may be required for a small proportion of patients for whom it may be
      life saving. Aggressive bronchodilator (continuous nebulised beta agonist) and
      anti-inflammatory therapy must continue throughout the period of mechanical
      ventilation. Recognised complications of mechanical ventilation include
      hypotension, barotrauma, and nosocomial pneumonia. Low ventilator respiratory
      rates, long expiratory times, and small tidal volumes help to prevent
      hyperinflation. Volatile anaesthetic agents may produce bronchodilation in
      patients resistant to beta agonists. Fatalities in acute asthmatics admitted to
      HDU/ICU are rare.

PMID- 12511730
TI  - Guidelines on prevention of venous thromboembolism during long haul flights.

PMID- 12511731
TI  - DOT for all patients with smear-positive pulmonary TB in London?

PMID- 12511732
TI  - Endotoxin: does it have a role in prevention of lung cancer.

PMID- 12511733
TI  - Urokinase in the treatment of childhood empyema.

PMID- 12511734
TI  - High incidence of cystic fibrosis in children born in Italy to Albanian
      immigrants.

PMID- 12511735
TI  - Familial hypercholesterolemia: stroke and the broader perspective.

PMID- 12511736
TI  - Stages and thresholds of hemodynamic failure.

PMID- 12511737
TI  - Why nondominant hand movements cause bilateral cortical activation in emission
      imaging.

PMID- 12511738
TI  - Beneficial effect of albumin therapy attributable to alpha1-acid glycoprotein?

PMID- 12511739
TI  - Does admission body temperature predict mortality after acute stroke?

PMID- 12511740
TI  - The ICH score: predicting mortality and functional outcome in an Asian
      population.

PMID- 12511741
TI  - Re: Telephone intervention with family caregivers of stroke survivors after
      rehabilitation.

PMID- 12511742
TI  - Converting enzyme inhibitor or AT1-receptor blocker for decreasing long-term
      mortality in patients with stroke history and renal dysfunction?

PMID- 12511743
TI  - Stroke in black South African HIV-positive patients: a prospective analysis.
AB  - BACKGROUND AND PURPOSE: Stroke associated with HIV infection is poorly
      characterized. In this study we analyze the association in a black African
      population. METHODS: The clinical, laboratory, and radiological characteristics
      of 35 hospital-based black South African, heterosexual, HIV-infected patients who
      did not abuse intravenous drugs and presented with strokes were prospectively
      studied. The patients were antiretroviral therapy naive. Patients with other
      intracranial space-occupying lesions were excluded from the study. RESULTS: The
      age range was 20 to 61 years (mean, 32.1 years). There were 21 female and 14 male
      patients, with a female to male ratio of 1.5:1. Cerebral infarction occurred in
      33 patients (94%) and intracerebral hemorrhage in 2 patients (6%). Underlying
      causes were identified in 30 of the 35 patients (86%) and included
      coagulopathies, meningitis, cardioembolism, and hypertension. The most common
      coagulopathy was protein S deficiency. No cause was found in 5 patients (14%).
      CONCLUSIONS: The results are similar to data from studies on young black African
      stroke patients who are HIV negative.

PMID- 12511744
TI  - Incidence and outcome of multiple intracranial aneurysms in a defined population.
AB  - BACKGROUND AND PURPOSE: Proportions of patients with single and multiple
      aneurysms among patients suffering from subarachnoid hemorrhage (SAH) are not
      well established. We evaluated these proportions and the differences in outcome
      between SAH patients with a single aneurysm and those with multiple aneurysms in
      a defined population. METHODS: Between 1989 and 1998, 2037 patients (age, 20 to
      89 years) with ruptured intracranial aneurysm were treated in 11 hospitals in
      Nagasaki Prefecture. Multiple aneurysms were found in 361 of these patients. Age-
      and sex-specific incidences of ruptured aneurysm per 100 000 people were
      calculated. RESULTS: For both single and multiple aneurysms, the incidences were
      significantly higher in women than in men 60 to 69 and 70 to 79 years of age. In
      every age category except 80 to 89 years, the frequency of multiple aneurysms was
      higher in women than in men. The overall frequency of multiple aneurysms was
      20.2% in women, which was significantly higher than the 12.4% in men (P<0.0001).
      In patients 70 to 89 years of age, outcome was significantly worse (in terms of
      surgical complications) in patients with multiple aneurysms (12.1%) than in
      patients with a single aneurysm (6.0%). CONCLUSIONS: Among all patients with SAH,
      women >or =50 years of age outnumber other age and sex categories. Female sex
      itself is also associated with an increased rate of multiple aneurysms among SAH
      patients. Among the elderly > or =70 years of age, prognosis is less favorable
      for SAH patients with multiple aneurysms than for those with a single aneurysm.

PMID- 12511745
TI  - Risk of fatal stroke in patients with treated familial hypercholesterolemia: a
      prospective registry study.
AB  - BACKGROUND AND PURPOSE: Although it is recognized that in heterozygous familial
      hypercholesterolemia, large extracranial carotid vessels are affected by
      atherosclerosis, the risk of fatal stroke after treatment with cholesterol
      lowering therapy remains uncertain. The goal of this study was to determine the
      risk of fatal stroke in patients with treated familial hypercholesterolemia.
      METHODS: A cohort of 1405 men and 1466 women with definite or possible
      heterozygous familial hypercholesterolemia was recruited from 21 outpatient lipid
      clinics in the United Kingdom. Patients were followed up prospectively from 1980
      to 1998 for 22 992 person-years for a median duration of 7.9 years (interquartile
      range, 4.9 to 12.0 years). The mortality rate was calculated, and the
      standardized mortality ratio for men and women 20 to 79 years of age was derived
      from the ratio of the observed deaths to the number expected in the general
      population of England and Wales (standardized mortality ratio=100 for the
      standard population). RESULTS: A total of 169 deaths occurred; 9 (5.3%) were a
      result of stroke. The mortality rate from stroke was 0.39 per 1000 person-years
      (95% confidence interval, 0.18 to 0.74), and the standardized mortality ratio for
      fatal stroke was nonsignificantly lower than in the general population (79; 95%
      CI, 36 to 150). CONCLUSIONS: The results suggest that patients with treated
      familial hypercholesterolemia are not at increased risk of fatal stroke. However,
      the possibility cannot be excluded that untreated individuals are at increased
      risk, which would be consistent with the evidence that familial
      hypercholesterolemia is a panvascular disease.

PMID- 12511746
TI  - Inherited thrombophilic disorders in young adults with ischemic stroke and patent
      foramen ovale.
AB  - BACKGROUND AND PURPOSE: The pathogenic link between patent foramen ovale (PFO)
      and stroke remains unknown in most cases. We investigated the association between
      inherited thrombophilic disorders and PFO-related strokes in a series of young
      adults in the setting of a case-control study. METHODS: We investigated 125
      consecutive subjects (age, 34.7+/-7.3 years) with ischemic stroke and 149 age-
      and sex-matched control subjects. PFO was assessed in all patients with
      transcranial Doppler sonography with intravenous injection of agitated saline
      according to a standardized protocol. Genetic analyses for the factor V
      (FV)(G1691A) mutation, the prothrombin (PT)(G20210A) variant, and the TT677
      genotype of methylenetetrahydrofolate reductase (MTHFR) were performed in all
      subjects. RESULTS: A pathogenic role of PFO was presumed in 36 patients (PFO+).
      Interatrial right-to-left shunt either was not detected or was considered
      unrelated to stroke occurrence in the remaining 89 patients (PFO-). The
      PT(G20210A) variant was more frequent in the PFO+ group compared with control
      subjects and the PFO- group (PFO+ versus control subjects, 11% versus 2%; 95% CI,
      0.04 to 0.94; PFO+ versus PFO-, 11% versus 1.1%; 95% CI, 1.09 to 109; P=0.047). A
      similar distribution was observed for subjects carrying either the PT(G20210A)
      variant or the FV(G1691A) mutation (PFO+ versus control subjects, 19.4% versus
      5.3%; 95% CI, 0.08 to 0.75; PFO+ versus PFO-, 19.4% versus 3.3%; 95% CI, 1.45 to
      26.1; P=0.021). Combined thrombophilic defects were observed in 3 subjects of the
      PFO+ group, in 2 control subjects (8.3% versus 1.3%; 95% CI, 0.01 to 0.66;
      P=0.015), and in 0 subjects in the PFO- group. A trend toward a difference in the
      frequency of the FV(G1691A) mutation between PFO+ and control subjects was found
      after bivariate analysis (11% versus 3.3%; P=0.068) but not after multinomial
      logistic regression analysis. No significant association was found in the
      distribution of the TT MTHFR genotype in the 3 groups. CONCLUSIONS: In young
      adults, the PT(G20210A) variant and, to a lesser extent, the FV(G1691A) mutation
      may represent risk factors for PFO-related cerebral infarcts. A role of systemic
      thrombophilic disorders in the pathogenesis of this specific subtype of stroke
      may be hypothesized.

PMID- 12511747
TI  - Autoregulatory response and CO2 reactivity of the basilar artery.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler has been extensively used to measure
      cerebrovascular control mechanisms, including autoregulation in humans and in
      patients with cerebrovascular diseases. There have been sufficient reports on the
      measurement of normal autoregulatory response (AR) and CO2 reactivity (CR) of the
      middle cerebral artery (MCA) but few reports of these indices for the basilar
      artery (BA). We measured AR and CR in the BA in healthy volunteers to determine
      normal values and compared them with simultaneous measurements made in the MCA.
      METHODS: Sixteen normal subjects were enrolled. Time-averaged mean velocities of
      maximum blood flow in the BA and MCA were continuously and simultaneously
      monitored by using transcranial Doppler along with continuous measurement of mean
      arterial blood pressure (MABP). Values were obtained during rest, alterations of
      end-tidal PaCO2 (ETCO2), and acute decrease and recovery of MABP. AR was
      evaluated by using the thigh cuff method and graded by the standard dynamic
      autoregulatory index (ARI), with values between 0 and 9. CR was measured as
      percentage change in time-averaged mean velocity per mm Hg ETCO2. RESULTS: The
      mean age of 16 subjects was 27.38+/-8.50 years. Average baseline values for MABP
      and ETCO2 were 82.29+/-7.10 and 42.75+/-3.77 mm Hg, respectively. Mean ARI was
      4.62+/-1.26 for the BA and was 4.77+/-1.23 for the MCA (n=15) (P=0.598). Average
      CR was 2.54+/-0.39%/mm Hg ETCO2 for the BA and 2.51+/-0.29%/mm Hg ETCO2 for the
      MCA (n=16) (P=0.686). CONCLUSIONS: Our study demonstrates that ARI and CR values
      for the BA are similar to those for the MCA.

PMID- 12511748
TI  - Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Matrix metalloproteinase-9 (MMP-9) activity has been
      associated with hemorrhagic transformation (HT) in experimental models of
      cerebral ischemia. Our aim was to investigate the relationship between MMP-9
      concentrations in blood within 24 hours of stroke onset and subsequent HT of
      cerebral infarction. METHODS: We studied 250 patients with a hemispheric ischemic
      stroke of 7.8+/-4.5 hours' duration. Early CT signs of cerebral infarction were
      evaluated on admission. The HT and infarct volume were analyzed from the CT
      performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked
      immunosorbent assay in blood samples obtained on admission. RESULTS: HT was
      observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14
      (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received
      anticoagulants before the second CT scan. Systolic and diastolic blood pressures,
      body temperature, frequency of early CT signs of ischemia (92% versus 22%), and
      treatment with anticoagulants (79% versus 37%) were significantly higher in the
      group with HT (P<0.001). Mean infarct volume was 126+/-60 cm(3) in the HT group
      and 90+/-68 cm3 in the group without HT (P=0.003). Median (quartiles) plasma MMP
      9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93]
      ng/mL, P<0.001), even in the 24 patients seen within 3 hours of symptom onset
      (P=0.014). MMP-9 levels > or =140 ng/mL had a positive and negative predictive
      value of HT of 61% and 97%, respectively. MMP-9 > or =140 ng/mL was associated
      with HT (odds ratio, 12; 95% confidence interval, 3 to 51; P<0.001) after
      adjustment for potential confounders and final infarct volume. CONCLUSIONS: High
      plasma MMP-9 concentration in the acute phase of a cerebral infarct is an
      independent biochemical predictor of HT in all stroke subtypes.

PMID- 12511749
TI  - Periodontal disease, tooth loss, and incidence of ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Periodontal and other infections have been suggested as
      potential risk factors for stroke. This study evaluates periodontal disease and
      tooth loss as risk factors for ischemic stroke. METHODS: The study population
      consisted of 41 380 men who were free of cardiovascular disease and diabetes at
      baseline. Periodontal disease history was assessed by mailed validated
      questionnaires. During 12 years of follow-up, stroke incidence was assessed and
      subclassified by use of medical history, medical records, and imaging reports.
      Hazard ratios (HRs) were adjusted for age, amount smoked, obesity, alcohol,
      exercise, family history of cardiovascular disease, multivitamin use, vitamin E
      use, profession, baseline reported hypertension, and hypercholesterolemia. Sex
      and socioeconomic status were inherently controlled for by restriction.
      Confounding variables were updated in the analyses for each 2-year follow-up
      interval. RESULTS: We documented 349 ischemic stroke cases during the follow-up
      period. Men who had < or =24 teeth at baseline were at a higher risk of stroke
      compared to men with > or =25 teeth (HR=1.57; 95% CI, 1.24 to 1.98). There was
      little evidence of an increased risk with recent tooth loss during follow-up. A
      modest association was seen between baseline periodontal disease history and
      ischemic stroke (HR=1.33; 95% CI, 1.03 to 1.70). Addition of dietary factors to
      the model changed the HR only slightly. CONCLUSIONS: Our results suggest that
      periodontal disease and fewer teeth may be associated with increased risk of
      ischemic stroke.

PMID- 12511750
TI  - Relation between serum albumin and carotid atherosclerosis: the NHLBI Family
      Heart Study.
AB  - BACKGROUND AND PURPOSE: Lower concentrations of albumin have been positively
      related to coronary disease. The aim of this project was to assess the
      association between serum albumin and carotid atherosclerosis. METHODS: B-mode
      ultrasound was used to assess carotid plaques and intima-media thickness (IMT)
      among white subjects from 592 randomly ascertained families in the National
      Heart, Lung, and Blood Institute Family Heart Study. Logistic regression was used
      to estimate prevalence odds ratios of any carotid plaques. RESULTS: Of the 2072
      persons studied, 47% were men. Higher serum albumin was associated with younger
      age, lower body mass index, and lower prevalence of hypertension and coronary
      disease. Lower serum albumin levels were not associated with an increased odds of
      carotid plaques. From the lowest to the highest quartile of albumin, multivariate
      adjusted odds ratios for the prevalence of any carotid plaques were 1.05 (95% CI,
      0.59 to 1.86), 1.34 (95% CI, 0.78 to 2.32), 1.03 (95% CI, 0.52 to 1.86), and 1.0
      (reference), respectively, in men and 0.71 (95% CI, 0.40 to 1.26), 0.76 (95% CI,
      0.42 to 1.36), 0.79 (95% CI, 0.46 to 1.36), and 1.0, respectively, in women.
      Similarly, in a linear regression model adjusted for demographic, lifestyle, and
      metabolic factors, serum albumin was not associated with carotid IMT. When the
      first 3 were compared with the highest quartile of serum albumin, regression
      coefficients for internal carotid IMT were 0.06458 (SE, 0.06408), 0.07205 (SE,
      0.05469), and 0.000773 (SE, 0.05687), respectively, for men and -0.01795 (SE,
      0.05085), -0.08501 (SE, 0.04800), and 0.009528 (SE, 0.04622), respectively, for
      women. CONCLUSIONS: Our data suggest that lower serum albumin levels are not
      associated with an increased odds of prevalent carotid atherosclerosis in either
      men or women.

PMID- 12511751
TI  - Early-onset carotid atherosclerosis is associated with increased intima-media
      thickness and elevated serum levels of inflammatory markers.
AB  - BACKGROUND AND PURPOSE: Several factors have been held responsible for the
      development of atherosclerosis. To avoid the masking effect of age, we evaluated
      correlates of carotid atherosclerosis in patients <55 years of age. METHODS:
      Plasma lipids, oxidative resistance of low-density lipoprotein, homocysteine,
      inflammatory markers, plasma viscosity, and red cell deformability were measured
      in fasting blood samples of 100 subjects: 45 patients with >30% stenosis of the
      internal carotid artery, 20 patients with carotid occlusion, and 35 control
      subjects. Stenosis and intima-media thickness (IMT) of the carotid artery were
      evaluated by duplex ultrasound. RESULTS: White blood cell (WBC) count, plasma
      fibrinogen, C-reactive protein (CRP), and lipoprotein(a) levels were
      significantly higher in patients than in control subjects, and patients had
      increased IMT (P<0.01 for all comparisons). There was a tendency for higher
      homocysteine levels in patients. Smokers had higher WBC, fibrinogen, and CRP
      levels. After the effect of smoking was controlled for, WBC count, natural
      logarithmic transform of homocysteine, and online-measured IMT remained
      significantly higher in patients than in control subjects. WBC, fibrinogen, and
      CRP levels were highest in the highest IMT quartile (P=0.012, P=0.007, and
      P=0.036, respectively). CONCLUSIONS: Inflammatory markers and homocysteine have a
      more important role than lipid factors in early-onset carotid atherosclerosis. We
      cannot recommend the measurement of low-density lipoprotein peroxidation as a
      routine screening test to identify high-risk patients for early-onset carotid
      atherosclerosis. The confounding effect of smoking on inflammatory markers should
      be considered in studies on atherosclerosis.

PMID- 12511752
TI  - Temporal relationship between apparent diffusion coefficient and absolute
      measurements of cerebral blood flow in acute stroke patients.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) has been established as
      a marker of acute ischemic brain injury. We sought to determine the relationship
      between cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) and to
      explore whether the elapsed time between MRI acquisition and symptom onset alters
      this relation in acute stroke patients. METHODS: Sixteen acute stroke patients
      were studied with DWI and perfusion-weighted imaging, from which ADC and CBF were
      calculated. ADC values were normalized (nADC) to the contralateral, nonischemic
      hemisphere and then correlated pixel by pixel with CBF within a region of
      interest defined by abnormal transit time. To explore potential temporal effects
      on the relationship between CBF and nADC, patients were divided into 2 groups
      based on the duration between symptom onset and MR imaging for data analysis:
      group A, 2 to 4 hours (n=8), and group B, 4.5 to 6.5 hours (n=8). RESULTS: nADC
      was plotted against CBF for each pixel in all 16 subjects, and a composite
      relationship was derived. After a gradual decline, an abrupt drop in nADC
      occurred below a CBF threshold value of 21 mL x min(-1) x 100 g(-1). When
      subjects were divided into early and late imaging groups, the group of patients
      imaged earlier (group A) had a lower threshold (15 mL x min(-1) x 100 g(-1)) than
      the group imaged later (group B, 24 mL x min(-1) x 100 g(-1)). CONCLUSIONS: Our
      results demonstrate that a relationship between nADC and CBF exists in the
      ischemic brain and that ADC values alone may provide useful information in
      predicting perfusion status. However, this relationship may change with elapsing
      time between stroke onset and imaging.

PMID- 12511753
TI  - Diagnostic accuracy of stroke referrals from primary care, emergency room
      physicians, and ambulance staff using the face arm speech test.
AB  - BACKGROUND AND PURPOSE: Timely referral of appropriate patients to acute stroke
      units is necessary for effective provision of skilled care. We compared the
      characteristics of referrals with suspected stroke to an academic acute stroke
      unit via 3 primary referral routes: ambulance paramedics using a rapid ambulance
      protocol and stroke recognition instrument, the Face Arm Speech Test; primary
      care doctors (PCDs); and emergency room (ER) referrals. METHODS: Patient
      characteristics, final diagnosis, and admission delay were recorded in all
      suspected acute stroke referrals in a 6-month period. RESULTS: Four hundred
      eighty-seven patients (356 strokes/transient ischemic attacks) were admitted by
      the 3 routes: 178 by ambulance, 216 by PCDs, and 93 through the ER. The
      proportion of nonstrokes admitted by each route was similar (23%, 29%, and 29%,
      respectively). Ambulance paramedics' stroke diagnosis was correct in 144 of 183
      (79%) stroke patients who initially presented to them. Thirty-nine of 66
      strokes/transient ischemic attacks referred via ER were taken there following
      initial ambulance assessment. Compared with PCDs, paramedics referred more total
      anterior circulation (39% versus 14%, P<0.0001) and fewer lacunar strokes (14%
      versus 31%, P<0.001) and admitted more patients (46% versus 12%, P<0.01) within 3
      hours of symptom onset. The most common nonstroke conditions were seizures,
      infections and confusion, cardiovascular collapse, and cerebral tumors.
      Paramedics admitted more patients with seizures. CONCLUSIONS: Misdiagnosis of
      stroke is common in the ER and by PCDs. Paramedics using the Face Arm Speech Test
      achieved high levels of detection and diagnostic accuracy of stroke.

PMID- 12511754
TI  - Contrast burst depletion imaging (CODIM): a new imaging procedure and analysis
      method for semiquantitative ultrasonic perfusion imaging.
AB  - BACKGROUND AND PURPOSE: Established methods of ultrasonic perfusion imaging using
      a bolus application of echo contrast agent provide only qualitative data because
      of various physical phenomena. This study was intended to investigate whether a
      new ultrasound perfusion imaging method termed contrast burst depletion imaging
      (CODIM) may provide semiquantitative measures of parenchymal perfusion
      independent of examination depth and acoustic energy distribution. METHODS: In a
      system with a constant concentration of contrast agent, analyzing the decrease in
      image intensity that occurs with microbubble-destructive imaging modes yields
      parameters that are considered to correlate with tissue perfusion. This method
      was first evaluated with a perfusion model that showed that the main resulting
      parameter "perfusion coefficient" (PC) is a monotonic nonlinear function of flow
      velocity. Seventeen human volunteers were then scanned according to this method
      with the use of 2 different contrast agents. Results were correlated with those
      from perfusion-weighted MRI examinations. RESULTS: The PC did not show
      significant differences in gray matter areas (ranging from 1.466x10(-2) x s(-1)
      to 1.641x10(-2) x s(-1)) of the brain despite different insonation depths (eg,
      ipsilateral and contralateral thalamus). In contrast, white matter exhibited
      significantly lower perfusion values in both imaging modes (PC: 0.604x10(-2) x s(
      1) to 0.745x10(-2) x s(-1); P<0.05). CONCLUSIONS: CODIM is a promising new tool
      of imaging parenchymal (brain) perfusion in healthy persons. The method provides
      semiquantitative and depth-independent perfusion parameters and in this way
      overcomes the limitations of the perfusion methods using a bolus kinetic. Further
      investigations must be done to evaluate the potential of the method in patients
      with perfusion deficits.

PMID- 12511755
TI  - Adaptive noninvasive assessment of intracranial pressure and cerebral
      autoregulation.
AB  - BACKGROUND AND PURPOSE: A mathematical model has previously been introduced to
      estimate noninvasively intracranial pressure (nICP). In the present multicenter
      study, we investigated the ability of model to adapt to the state of cerebral
      autoregulation (SCA). This modification was intended to improve the quality of
      nICP estimation and noninvasive assessment of pressure reactivity of the
      cerebrovascular system. METHODS: We studied 145 patients after severe head
      injuries or stroke. All patients had direct ICP, arterial blood pressure (ABP),
      and transcranial Doppler middle cerebral artery blood flow velocity (FV)
      monitored. The SCA was assessed by moving correlation (Mx index) of cerebral
      perfusion pressure (CPP=ABP-ICP) and cerebral blood flow velocity and correlation
      of ABP and ICP (PRx index). nICP was calculated from ABP and FV waveforms. When
      nICP was used instead of ICP, the SCA was continuously estimated, and the model
      was dynamically adapted to the SCA. RESULTS: High and moderate correlations
      between invasively (Mx, PRx) and noninvasively (nMx, nPRx) estimated
      autoregulation indexes were observed (Mx: R=0.90, P<0.001; PRx: R=0.62, P<0.001).
      Values of Mx and nMx indicated contradictory SCA in 4 of 167 evaluated
      recordings; values of PRx and nPRx were contradictory in 27 recordings. When the
      model was adapted to the SCA, the mean error of ICP estimation decreased
      significantly (P<0.005). CONCLUSIONS: Continuous adaptation of the model to SCA
      improves the accuracy of noninvasive estimation of ICP and ICP dynamics. The same
      model provides a noninvasive and continuous assessment of SCA.

PMID- 12511756
TI  - Angiographic dilatation and branch extension of the anterior choroidal and
      posterior communicating arteries are predictors of hemorrhage in adult moyamoya
      patients.
AB  - BACKGROUND AND PURPOSE: The cause of intracranial bleeding in moyamoya disease
      patients is still unknown. To identify factors that contribute to bleeding, we
      assessed the angiographic findings of moyamoya disease patients. METHODS: We
      examined angiograms obtained from 107 moyamoya patients; 70 manifested ischemic
      and 37 had hemorrhagic lesions. Patients with intracerebral aneurysms or both
      hemorrhagic and ischemic lesions in the same cerebral hemisphere were not
      included. Patients were divided into those <20 years of age (n=47) and those > or
      =20 years of age (n=60). The right and left hemispheres in each patient were
      individually classified as hemorrhagic, ischemic, or asymptomatic. Each
      hemisphere was assessed for dilatation and branch extension of the anterior
      choroidal artery (AChA) and posterior communicating artery (P-CoM) and for the
      degree of proliferation of basal moyamoya vessels. These data were then
      statistically analyzed for correlation with intracranial bleeding events.
      RESULTS: The degree of proliferation of basal moyamoya vessels was not
      statistically correlated with hemorrhagic events. On the other hand, there was a
      correlation between hemorrhage and dilatation and abnormal branching of the AChA.
      In 27 of 37 hemorrhagic hemispheres (73.0%), this artery was dilated, and its
      abnormal branches served as collateral supply vessels to other regions. This
      phenomenon was observed in 4 of 5 hemorrhagic hemispheres from young patients; it
      was noted in fewer than one third of ischemic and asymptomatic hemispheres from
      this age group. Similarly, 71.9% of hemorrhagic hemispheres from adult patients
      manifested AChA dilatation and branching, and the difference between hemorrhagic
      hemispheres and those that were ischemic or asymptomatic was statistically
      significant (P<0.01). Although the incidence of dilatation and abnormal branching
      of the P-CoM was relatively low in hemorrhagic hemispheres from adult patients
      (18.8%), it was significantly higher than in the ischemic and asymptomatic
      hemispheres from this age group. Using dilatation and abnormal branching of the
      AChA and/or P-CoM as assessment criteria, we obtained high specificity (86.4%)
      and sensitivity (84.4%) for hemorrhagic events in adult moyamoya patients.
      CONCLUSIONS: In adult moyamoya patients, dilatation and abnormal branching of the
      AChA and/or P-CoM are strong predictors of hemorrhagic events.

PMID- 12511757
TI  - Risk factors for aneurysmal subarachnoid hemorrhage in Aomori, Japan.
AB  - BACKGROUND AND PURPOSE: Japan is known to have an incidence of aneurysmal
      subarachnoid hemorrhage (SAH) as high as that in Finland, where SAH is especially
      common. However, the risk factors for SAH in Japan are unknown. The purpose of
      this study was to identify the risk factors and then examine their possible roles
      in cases of SAH in Japan. METHODS: Case-control data were collected in the Aomori
      prefecture between June 2000 and May 2001 and in the Shimokita area between 1989
      and 1998. A history of hypertension, cigarette smoking, alcohol consumption,
      hypercholesterolemia, and diabetes mellitus were examined as possible risk
      factors for SAH by using stepwise logistic regression analysis. RESULTS: Stepwise
      logistic regression analysis showed that a history of hypertension and current
      smoking increased the risk of SAH and that a history of hypercholesterolemia
      decreased the risk of SAH. Alcohol consumption and a history of diabetes mellitus
      were excluded from the model, because their log-likelihood ratios were not
      significant. The adjusted odds ratios, obtained by forcing matching factors, were
      2.29 for a history of hypertension (95% CI, 1.66 to 3.16), 3.12 for current
      smoking (95% CI, 2.05 to 4.77), and 0.41 for a history of hypercholesterolemia
      (95% CI, 0.24 to 0.71). The prevalence of hypertension in control subjects was
      27% in men and 31% in women, whereas the prevalence of cigarette smoking in
      control subjects was 46% in men and 9% in women. CONCLUSIONS: Hypertension and
      cigarette smoking seem to be independent risk factors for SAH in Japan. The high
      prevalence of hypertension in both sexes and the high prevalence of cigarette
      smoking in men in the general population might contribute to the high incidence
      of SAH in Japan.

PMID- 12511758
TI  - Admitting acute ischemic stroke patients to a stroke care monitoring unit versus
      a conventional stroke unit: a randomized pilot study.
AB  - BACKGROUND AND PURPOSE: Pathophysiological considerations and observational
      studies indicate that elevated body temperature, hypoxia, hypotension, and
      cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain
      damage and worsen outcome. METHODS: Both units were organized with the same
      standard care and multidisciplinary approach to nursing and rehabilitation. A
      blinded observer assessed functional outcome at 3 months with the modified Rankin
      scale (mRS) and Barthel Index (BI). End points were (1) poor outcome, defined as
      either mRS > or =4 or BI <60 or the need for institutional care and (2)
      mortality. RESULTS: Fifty-four patients meeting the inclusion criteria were
      randomized. The groups were well matched for baseline characteristics, stroke
      subtype, stroke severity, vascular risk factors, and prognostic factors. Poor
      outcome was seen in 7 (25.9%) patients in the SCMU group and in 13 (48.1%) in the
      SU group (P=0.16). Mortality was lower in the SCMU group than in the SU group (1
      [3.7%] vs 7 [25.9%]; odds ratio, 0.11 [95% CI, 0.02 to 0.96], P=0.05).
      CONCLUSIONS: This pilot study suggests that admission of acute stroke patients to
      an SCMU may reduce mortality and poor outcome. A larger trial is required to
      confirm these findings.

PMID- 12511759
TI  - Determination of lipid profiles and use of statins in patients with ischemic
      stroke or transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Statins reduce the risk of myocardial infarction and
      stroke in patients with vascular disease. Inappropriate serum lipid determination
      and underuse of statins have been documented in patients with coronary artery
      disease. Evaluation of hyperlipidemia and treatment with statins in patients with
      recent ischemic cerebrovascular events have not yet been investigated. METHODS:
      We determined the frequency of total cholesterol (TC) and low-density lipoprotein
      cholesterol measurements and the use of statins in a multicenter prospective
      cohort study of 1743 patients with acute ischemic stroke or transient ischemic
      attack (TIA). Using multivariate logistic regression analysis, we determined the
      influence of several clinical variables on lipid measurements and the
      prescription of statins at hospital discharge. RESULTS: TC was measured in 90%
      and low-density lipoprotein cholesterol was measured in 48% of the patients.
      Differences between the centers accounted for most of the observed variability in
      a multivariate model. Statin prescription also varied widely between the centers.
      The prescription of a statin at discharge was most strongly associated with
      statin intake before the event and with increasing TC levels; elderly patients
      received statins less often. Coronary artery disease, peripheral artery disease,
      and other manifestations of atherosclerosis were not independently associated
      with the use of statins; 68% of the patients with manifest atherosclerosis and TC
      levels >200 mg/dL were discharged without a statin. CONCLUSIONS: The
      determination of serum lipid profiles varies widely between different centers.
      Statins are highly underused in patients with recent ischemic stroke or TIA,
      particularly in those in whom statins are indicated according to existing
      recommendations (eg, patients with additional coronary artery disease and
      hypercholesterolemia). Currently, international guidelines concerning the use of
      statins are not adequately implemented in clinical practice in patients with
      stroke or TIA.

PMID- 12511760
TI  - Cognitive behavioral psychotherapy for depression following stroke: a randomized
      controlled trial.
AB  - BACKGROUND AND PURPOSE: There is inconclusive evidence of the effectiveness of
      psychological interventions for depression after stroke. We report the results
      from a randomized controlled trial of cognitive behavioral therapy (CBT).
      METHODS: Stroke patients admitted to hospital were invited to complete mood
      questionnaires 1, 3 and 6 months after stroke. Patients who were depressed were
      invited to take part in a trial and randomly allocated to receive CBT (n=39), an
      attention placebo intervention (n= 43), or standard care (n=41). Outcome
      assessments were undertaken at 3 and 6 months after recruitment, on the Beck
      Depression Inventory, Wakefield Depression Inventory, Extended Activities of
      Daily Living scale, London Handicap Scale, and a rating of satisfaction with
      care. RESULTS: There were no significant differences between the groups in
      patients' mood, independence in instrumental activities of daily living,
      handicap, or satisfaction with care. CONCLUSIONS: CBT in the treatment of
      depression following stroke was found to be ineffective in this study. However,
      because of the small sample size, method of recruitment, and selection criteria,
      further randomized trials are required.

PMID- 12511761
TI  - Evaluation of a stroke family support organiser: a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: There is inconclusive evidence of the effectiveness of
      the Stroke Family Support Organiser (FSO) service. We report the results from a
      randomized controlled trial of the service. METHODS: Stroke patients admitted to
      hospital and their informal caregivers were randomly allocated to receive the FSO
      service (n=126) or standard care (n=124). Outcome assessments were undertaken 4
      and 9 months after recruitment with the General Health Questionnaire 12, Carer
      Strain Index, Barthel Index, Extended Activities of Daily Living scale, and a
      specially designed questionnaire to determine knowledge of stroke and
      satisfaction with services. RESULTS: There were no significant differences
      between groups in patients' mood and independence in personal or instrumental
      activities of daily living or caregivers' mood, strain, or independence. Patients
      in the intervention group were significantly more knowledgeable about whom to
      contact for stroke information, reducing the risk of stroke, practical help,
      community services, and emotional support. Patients in the intervention group
      were also significantly more satisfied with the stroke information received.
      Caregivers in the intervention group were significantly more knowledgeable about
      whom to contact for information on stroke, reducing the risk of stroke, community
      services, and emotional support. Caregivers in the intervention group were also
      significantly more satisfied with stroke information. CONCLUSIONS: The FSO
      service had no significant effect on mood, independence in activities of daily
      living, or reduction in caregiver strain, but it did increase knowledge of stroke
      and satisfaction with that knowledge. The results may not be representative of
      all FSO services, and the sample was small relative to the heterogeneity of the
      participants. However, results suggest that the policies and training procedures
      of FSOs need to be evaluated to ensure that a cost-effective service is being
      provided to stroke patients and their caregivers.

PMID- 12511762
TI  - Poor outcome after first-ever stroke: predictors for death, dependency, and
      recurrent stroke within the first year.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to define predictors of
      poor outcome after a first-ever stroke. We studied risk factors and stroke
      severity at baseline in relationship to death, dependency, and stroke recurrence
      within a year after the event. METHODS: The study included a community-based
      cohort of first-ever stroke patients. Subarachnoid hemorrhage was not included.
      All patients (n=377) were subjected to investigations regarding risk factors.
      Stroke severity was evaluated with the National Institutes of Health Stroke
      Scale, and dependency was defined according to the modified Rankin Scale.
      Multivariate regression models were used to analyze predictors of survival,
      dependency, and stroke recurrence. The following independent variables were used:
      age, sex, cohabitation status, cigarette smoking, dementia, hypertension,
      ischemic heart disease, heart failure, atrial fibrillation, diabetes mellitus,
      transitory ischemic attack, peripheral atherosclerosis, and stroke severity.
      RESULTS: The 1-year mortality was 33%. After 1 year, 37% of the survivors were
      dependent; 9% of survivors had a recurrent stroke within a year. Dementia, age,
      stroke severity, and atrial fibrillation were associated with death within a
      year. Dependency was associated with age, stroke severity, and heart failure.
      Stroke recurrence was predicted by age and dementia. CONCLUSIONS: In addition to
      age and stroke severity, heart diseases and dementia before the stroke seem to
      have an impact on mortality and recurrence after 1 year. Finding and, when
      possible, treating these prestroke conditions may affect stroke morbidity and
      mortality favorably.

PMID- 12511763
TI  - Performance of a statistical model to predict stroke outcome in the context of a
      large, simple, randomized, controlled trial of feeding.
AB  - BACKGROUND AND PURPOSE: Statistical models to predict the outcome of stroke
      patients have several uses. Their utility depends on their predictive accuracy in
      patients other than those on whom they were developed (ie, external validity). We
      sought to test the external validity of some recently described models in
      patients enrolled in the FOOD (Feed Or Ordinary Diet) trial: a large randomized
      trial evaluating feeding policies in patients with stroke. METHODS: The
      predictive variables were collected during a telephone call to randomize the
      patient a median of 5 days after stroke onset. Patients were followed up 6 months
      later to establish their survival, functional status, and residence. Charts were
      plotted to demonstrate the discrimination and calibration of the models. RESULTS:
      The models performed well in the first 2955 patients enrolled and followed up in
      the FOOD trial. The area under the receiver operating characteristic curves
      varied between 0.78 and 0.81 (with 0.5 indicating no discrimination and 1.0
      indicating perfect discrimination). The discrimination was marginally better for
      patients enrolled within the first day of stroke than later. The models tended to
      provide rather pessimistic predictions in all groups except those predicted to
      have a high likelihood of surviving free of dependency. CONCLUSIONS: As one might
      predict, the discriminatory power in the selected cohort of trial patients was
      marginally less good than in previously studied unselected cohorts used to test
      their external validity. These models provide a well-tested tool for
      stratification in trials, comparing outcomes in different cohorts and examining
      the additional predictive power of novel factors.

PMID- 12511764
TI  - Utility of the NIH Stroke Scale as a predictor of hospital disposition.
AB  - BACKGROUND AND PURPOSE: Early identification of stroke patients in need of
      rehabilitation or long-term nursing facility (NF) care may promote more efficient
      use of health care resources and lead to better outcomes. The NIH Stroke Scale
      (NIHSS) is an attractive candidate predictor of disposition because it is widely
      used, is easily learned, and can be performed rapidly on admission. METHODS: We
      present a retrospective study of stroke patients admitted within 24 hours of
      symptom onset to a university hospital from March through June 2000. Medical
      records were reviewed for demographic information, stroke type, prestroke living
      arrangement and independence, initial NIHSS, and medical complications during
      hospitalization. RESULTS: Among 94 patients evaluated during the study period,
      59% were discharged home, 30% to rehabilitation, and 11% to NF. In multivariate
      analyses, disposition was associated only with initial NIHSS. For each 1-point
      increase in NIHSS, the likelihood of going home was significantly reduced (odds
      ratio, 0.79; 95% CI, 0.70 to 0.89, P<0.001). Categorization of NIHSS was also
      predictive of disposition, with NIHSS < or =5 being most strongly associated with
      discharge home, NIHSS 6 to 13 with rehabilitation, and NIHSS >13 with NF
      (P<0.001). Although no other baseline characteristics predicted disposition,
      major medical complications during hospitalization tended to reduce the odds of
      going home (odds ratio, 0.30; 95% CI, 0.08 to 1.0, P=0.07). CONCLUSION: The NIHSS
      predicts postacute care disposition among stroke patients. Predicting disposition
      on the first day of admission may facilitate the time-consuming and costly
      process of securing a bed at rehabilitation or NF, and perhaps decrease
      unnecessary length of stay in acute care settings.

PMID- 12511765
TI  - Poststroke depression: an 18-month follow-up.
AB  - BACKGROUND AND PURPOSE: This prospective study was designed to examine the
      course, associates, and predictors of depressive symptoms during the first 18
      months after stroke. METHODS: A total of 100 patients were followed up for 18
      months after stroke. Depressive symptoms were assessed at 2 weeks and 2, 6, 12,
      and 18 months after stroke with the Beck Depression Inventory and the Hamilton
      Rating Scale for Depression, and diagnoses were performed using criteria outlined
      in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition
      Revised. Stroke severity was assessed with the Scandinavian Stroke Scale and
      cognitive functions with a comprehensive neuropsychological battery. Patients
      participated in a randomized clinical trial of antidepressive medication.
      RESULTS: In all, 54% of patients felt at least mildly depressive at some time
      during the follow-up; 46% of those who were depressive during the first 2 months
      were also depressive at 12 and/or 18 months. Only 12% of patients were depressive
      for the first time at 12 or 18 months. The male sex was associated with a more
      negative change in depressive symptoms during the follow-up. Older age was
      associated with depressive symptoms during the first 2 months, stroke severity
      from 6 to 12 months, and the male sex at 18 months. Depressive symptoms were
      unrelated to the lesion location. CONCLUSIONS: Depressive symptoms are frequent
      and they often have a chronic course. Depression is associated with stroke
      severity and functional impairment, and with the male sex at 18 months. Attention
      should be focused on the long-term prognosis of mood disturbances and adaptation.

PMID- 12511766
TI  - New-onset fecal incontinence after stroke: prevalence, natural history, risk
      factors, and impact.
AB  - BACKGROUND AND PURPOSE: Fecal incontinence (FI) is a common complication after
      stroke, yet epidemiological research into this distressing condition is limited.
      The purpose of this study was to describe the prevalence, natural history,
      associations, and impact of new-onset FI after stroke. METHODS: Stroke patients
      in the community-based South London Stroke Register (January 1995 to 2000)
      without preexisting FI were characterized regarding bowel continence at 7 to 10
      days, 3 months, and 1 and 3 years after stroke. FI was defined as any degree of
      bowel leakage. RESULTS: Prevalence of poststroke FI was 30% (7 to 10 days), 11%
      (3 months), 11% (1 year), and 15% (3 years). One third of patients with FI at 3
      months were continent by 1 year; conversely, 63% incontinent at 1 year had been
      continent at 3 months. Characteristics of 91 patients with FI and 755 without FI
      at 3 months were compared using multiple logistic regression. Acute stroke
      associations of neglect (adjusted odds ratio [OR], 1.9; 95% CI, 1.0 to 3.5) and
      initial urinary incontinence (OR, 6.2; 95% CI, 3.2 to 11.9) were no longer
      significant after adjustment for clinical factors at 3 months. Final independent
      associations were anticholinergic drug use (OR, 3.1; 95% CI, 1.1 to 10.2) and
      needing help with toilet use (OR, 3.5; 95% CI, 1.4 to 17.3). FI at 3 months
      increased the risk of long-term placement (28% vs 6%) and death within 1 year
      (20% vs 8%). CONCLUSIONS: New-onset FI in stroke survivors is common but may be
      transient. Modifiable risk factors for FI 3 months after stroke are constipating
      drug use and difficulty with toilet access, raising implications for developing
      treatment and prevention strategies.

PMID- 12511767
TI  - Establishing data elements for the Paul Coverdell National Acute Stroke Registry:
      Part 1: proceedings of an expert panel.
AB  - BACKGROUND AND PURPOSE: Stroke is the third-leading cause of death and a leading
      cause of disability in adults in the United States. In recent years, leaders in
      the stroke care community identified a national registry as a critical tool to
      monitor the practice of evidence-based medicine for acute stroke patients and to
      target areas for continuous quality of care improvements. An expert panel was
      convened by the Centers for Disease Control and Prevention to recommend a
      standard list of data elements to be considered during development of prototypes
      of the Paul Coverdell National Acute Stroke Registry. METHODS: A
      multidisciplinary panel of representatives of the Brain Attack Coalition,
      professional associations, nonprofit stroke organizations, and federal health
      agencies convened in February 2001 to recommend key data elements. Agreement was
      reached among all participants before an element was added to the list. RESULTS:
      The recommended elements included patient-level data to track the process of
      delivering stroke care from symptom onset through transport to the hospital,
      emergency department diagnostic evaluation, use of thrombolytic therapy when
      indicated, other aspects of acute care, referral to rehabilitation services, and
      90-day follow-up. Hospital-level measures pertaining to stroke center guidelines
      were also recommended to augment patient-level data. CONCLUSIONS: Routine
      monitoring of the suggested parameters could promote community awareness
      campaigns, support quality improvement interventions for stroke care and stroke
      prevention in each state, and guide professional education in hospital and
      emergency system settings. Such efforts would reduce disability and death among
      stroke patients.

PMID- 12511768
TI  - HMG-CoA reductase inhibitor has protective effects against stroke events in
      stroke-prone spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Recent clinical studies suggest that 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert
      protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia
      model produced by occlusion of the middle cerebral artery, statins were shown to
      reduce infarct size. However, the effect of statins on hypertension-based stroke
      is unknown. The purpose of this study is to clarify the effect of a statin on
      stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both
      cerebral hemorrhage and infarction occur. METHODS: We treated SHR-SP chronically
      from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle. The
      physiological parameters, the incidence of stroke-associated symptoms, and
      mortality were assessed. RESULTS: At 14 weeks of age, the incidence (13+/-3%
      versus 37+/-8%; P<0.01) and the size of stroke (1.6+/-0.2 versus 2.2+/-0.1
      arbitrary units; P<0.01) were significantly decreased by cerivastatin, although
      blood pressure and plasma cholesterol levels were not different. Moreover, stroke
      associated symptoms and early mortality of SHR-SP were markedly reduced in the
      statin-treated group (mortality at the age of 15 weeks: 15% versus 50%; P<0.05).
      Statin treatment significantly reduced superoxide production from nonstroke
      parenchyma of brain and infiltration of inflammatory cells to the stroke lesions.
      CONCLUSIONS: Our data show that a high dose of statin exerts protection against
      hypertension-based stroke and ameliorates the disease severity via inhibition of
      superoxide production and modulation of inflammation in brain.

PMID- 12511769
TI  - Ischemic preconditioning in the hippocampus of a knockout mouse lacking SUR1
      based K(ATP) channels.
AB  - BACKGROUND AND PURPOSE: ATP-sensitive K+ (K(ATP)) channels have been implicated
      in the mechanism of neuronal ischemic preconditioning. To evaluate the role of
      neuronal/beta-cell-type K(ATP) channels, SUR1 null (Sur1KO) mice lacking
      (K(IR)6.x/SUR1)(4) K(ATP) channels were subjected to a preconditioning protocol
      with the use of double carotid occlusion. METHODS: Wild-type C57BL/6 and Sur1KO
      mice were subjected to a double carotid block for 40 minutes with or without a 20
      minute preconditioning block. After a 10-day reperfusion period, damage was
      assessed histologically in the hippocampal CA1, CA2, and CA3 areas and in the
      dentate gyrus. The neuroprotective effects of intracerebroventricular injections
      of diazoxide, which selectively affects mitochondria versus opening SUR1-type
      K(ATP) channels, and 5-hydroxydecanoate, a selective blocker of mitoK(ATP)
      channels, were evaluated with the same protocol. RESULTS: Neurons in the CA1
      region of both Sur1KO and wild-type animals subjected to a 20-minute ischemic
      insult were protected equally from neuronal damage produced by a subsequent 40
      minute ischemic period. Pretreatment with diazoxide protected both Sur1KO and
      wild-type neurons, while 5-hydroxydecanoate augmented neurodegeneration in both
      strains of animals when administered before a 20-minute bout of ischemia.
      CONCLUSIONS: SUR1-based K(ATP) channels are not obligatory for neuronal
      preconditioning or augmentation of neurodegeneration by 5-hydroxydecanoate.

PMID- 12511770
TI  - CP-465,022, a selective noncompetitive AMPA receptor antagonist, blocks AMPA
      receptors but is not neuroprotective in vivo.
AB  - BACKGROUND AND PURPOSE: Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptor inhibition has been hypothesized to provide neuroprotective
      efficacy after cerebral ischemia on the basis of the activity in experimental
      ischemia models of a variety of compounds with varying selectivity for AMPA over
      other glutamate receptor subtypes. CP-465,022 is a new, potent, and selective
      noncompetitive AMPA receptor antagonist. The present study investigated the
      ability of this compound to reduce neuronal loss after experimental cerebral
      ischemia to probe the neuroprotective potential of AMPA receptor inhibition.
      METHODS: To demonstrate that CP-465,022 gains access to the brain, the effects of
      systemic administration of CP-465,022 were investigated on AMPA receptor-mediated
      electrophysiological responses in hippocampus and on chemically induced seizures
      in rats. The compound was then investigated for neuroprotective efficacy in rat
      global and focal ischemia models at doses demonstrated to be maximally effective
      in the electrophysiology and seizure models. RESULTS: CP-465,022 potently and
      efficaciously inhibited AMPA receptor-mediated hippocampal synaptic transmission
      and the induction of seizures. However, at comparable doses, CP-465,022 failed to
      prevent CA1 neuron loss after brief global ischemia or to reduce infarct volume
      after temporary middle cerebral artery occlusion. CONCLUSIONS: Given the high
      selectivity of CP-465,022 for AMPA over kainate and N-methyl-D-aspartate subtypes
      of glutamate receptors, the lack of neuroprotective efficacy of the compound
      calls into question the neuroprotective efficacy of AMPA receptor inhibition
      after ischemia.

PMID- 12511771
TI  - Differential regulation of thrombospondin-1 and thrombospondin-2 after focal
      cerebral ischemia/reperfusion.
AB  - BACKGROUND AND PURPOSE: Angiogenesis occurs after cerebral ischemia, and the
      extent of angiogenesis has been correlated with survival in stroke patients.
      However, postischemic angiogenesis is short-lived and may be completely
      terminated within a few weeks after ischemic insult. The molecular mechanism
      underlying the dissolution of postischemic angiogenic processes is poorly
      understood. Although the expression of angiogenic genes has been studied in
      ischemic stroke models, the activation of angiostatic genes after cerebral
      ischemia has not been investigated. Thrombospondin (TSP)-1 and TSP-2 are
      naturally occurring angiostatic factors, which inhibit angiogenesis in vivo. The
      aim of the present study was to explore the expression of TSP-1 and TSP-2 in
      relation to the evolution of angiogenic process in a focal ischemia model in
      rats. METHODS: Rats underwent cortical ischemia in the middle cerebral artery
      territory for 60 minutes and reperfusion for up to 2 weeks. Northern and Western
      blot analysis were used to study the temporal profile of TSP-1 and TSP-2
      expression at the mRNA and protein level, respectively. In situ hybridization and
      immunohistochemical studies were used to examine the spatial expression patterns.
      Double immunostaining was applied to define the cellular origins of TSP-1 and TSP
      2. RESULTS: A biphasic expression of TSP-1 was noted after ischemia, peaking at 1
      and 72 hours. Endothelial cells in the leptomeninges were the only source of the
      first TSP-1 peak, whereas endothelial, glial, neuronal, and macrophage cells
      contributed to the second peak of TSP-1 expression. TSP-2 expression occurred
      much later and in a monophasic manner, peaking 2 weeks after ischemia. TSP-2
      immunoreactivity was observed in endothelial, neuronal, and macrophage, but not
      glial, cells. TSP-1 was expressed before the peak of angiogenesis, whereas robust
      TSP-2 expression occurred at the peak of angiogenesis and continued into the
      period when angiogenesis had completely resolved. CONCLUSIONS: Robust expression
      of TSP-1 and TSP-2, 2 major angiostatic factors, was noted in the ischemic brain
      with different temporal expression profiles from different cellular origins. The
      expression of these angiostatic factors, especially TSP-2, likely contributes to
      the spontaneous resolution of postischemic angiogenesis. Further studies are
      needed to explore the molecular mechanisms that regulate the balance of
      angiogenic and angiostatic factors in the ischemic brain.

PMID- 12511772
TI  - In vitro measurement of fluid-induced wall shear stress in unruptured cerebral
      aneurysms harboring blebs.
AB  - BACKGROUND AND PURPOSE: Little attention has been focused on the role of fluid
      induced wall shear stress in fully developed cerebral aneurysms. The purpose of
      this study is to evaluate the alternation and distribution of wall shear stress
      over 1 cardiac cycle in patients' aneurysms. METHODS: A middle cerebral artery
      aneurysm and a basilar tip aneurysm with localized outpouching (blebs) in their
      domes were selected for this study. With the use of a stereo lithography machine,
      geometrically realistic aneurysm models were created on the basis of 3
      dimensional CT angiograms. In vitro shearing velocity measurement was conducted
      with the use of laser-Doppler velocimetry at multiple points on the aneurysmal
      wall to calculate the value of wall shear stress. The wall shear stress was
      documented at multiple points in the aneurysm inflow zone, dome, and outflow
      zone. RESULTS: Distribution of wall shear stress was not uniform in the aneurysm
      walls, and particular regions were exposed to relatively high wall shear stress.
      The wall shear stress changed dynamically throughout 1 cardiac cycle at the point
      where a high value of wall shear stress was noted. The blebs of both aneurysms
      were exposed to high wall shear stress. Unlike previous reports in which an ideal
      spherical aneurysm model was used, the aneurysm inflow zone was not exposed to
      high shear stress. CONCLUSIONS: In vitro aneurysm models based on the patients'
      angiograms allowed us to conduct a more realistic evaluation of wall shear stress
      in the aneurysms harboring blebs. These results provide us with further
      indications of the correlation of wall shear stress with the natural history of
      cerebral aneurysms.

PMID- 12511773
TI  - Cerebral hypoperfusion and delayed hippocampal response after induction of adult
      kaolin hydrocephalus.
AB  - BACKGROUND AND PURPOSE: In chronic hydrocephalus, a role for tissue hypoxia
      resulting from cerebrovascular compression is suggested. The purpose of this
      study was to evaluate whether changes in cerebral blood flow (CBF) in the time
      course of adult kaolin-induced hydrocephalus correlated with immunohistochemical
      neuronal responses. METHODS: In 46 adult Sprague-Dawley rats, kaolin
      hydrocephalus was induced and immunostaining of neurofilament protein (NF68),
      synaptophysin (SYN38), and neuronal nitric oxide synthase (NOS) was performed at
      2 (short term), 4 (intermediate term), and 6 and 8 (long term) weeks. Local CBF
      was measured quantitatively by [14C]iodoantipyrine ([14C]IAP) autoradiography in
      the short-term stage and in both long-term stages. RESULTS: At 2 weeks, neuronal
      NOS immunoreactivity was globally increased in cortical areas and within the
      hippocampus. Four weeks after hydrocephalus induction, a reactive increase of
      SYN38 and NF68 immunoreactivity in the periventricular cortex was seen. At 6 and
      8 weeks, when the ventricular size was decreasing, immunohistochemical changes in
      the hippocampus became most evident. A maintained toxic NOS reactivity in the CA1
      subfield was accompanied by a loss of NF68 staining. In the CA3 subfield,
      however, focal increases in NF68 and SYN38 immunoreactivity were found. Cortical
      and hippocampal blood flow showed prolonged decreases of 25% to 55% compared with
      control animals. At 8 weeks, control levels were reached. CONCLUSIONS: The
      observed temporary CBF decrease appears to correlate with an early global
      neuronal ischemic response. In addition, it may also account for the delayed
      selective response of ischemia-vulnerable structures, eg, hippocampus, in chronic
      adult kaolin-induced hydrocephalus.

PMID- 12511774
TI  - Predicting outcome in ischemic stroke: external validation of predictive risk
      models.
AB  - BACKGROUND: Six multivariable models predicting 3-month outcome of acute ischemic
      stroke have been developed and internally validated previously. The purpose of
      this study was to externally validate the previous models in an independent data
      set. SUMMARY OF REPORT: We predicted outcomes for 299 patients with ischemic
      stroke who received placebo in the National Institute of Neurological Disorders
      and Stroke rt-PA trial. The model equations used 6 acute clinical variables and
      head CT infarct volume at 1 week as independent variables and 3-month National
      Institutes of Health Stroke Scale, Barthel Index, and Glasgow Outcome Scale as
      dependent variables. Previously developed model equations were used to forecast
      excellent and devastating outcome for subjects in the placebo tissue plasminogen
      activator data set. Area under the receiver operator characteristic curve was
      used to measure discrimination, and calibration charts were used to measure
      calibration. The validation data set patients were more severely ill (National
      Institutes of Health Stroke Scale and infarct volume) than the model development
      subjects. Area under the receiver operator characteristic curves demonstrated
      remarkably little degradation in the validation data set and ranged from 0.75 to
      0.89. Calibration curves showed fair to good calibration. CONCLUSIONS: Our models
      have demonstrated excellent discrimination and acceptable calibration in an
      external data set. Development and validation of improved models using variables
      that are all available acutely are necessary.

PMID- 12511775
TI  - Yield of screening for CADASIL mutations in lacunar stroke and leukoaraiosis.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy subcortical
      infarcts and leukoencephalopathy (CADASIL) is a monogenic disorder typified by
      early onset lacunar strokes, subcortical dementia, psychiatric disturbances, and
      migraine. Mutations in the Notch3 gene are responsible. Atypical phenotypes have
      been recognized, and the disease is probably underdiagnosed in the wider stroke
      population. Therefore, we determined the yield of screening for Notch3 mutations
      in lacunar stroke with or without leukoaraiosis. METHODS: Two hundred eighteen
      consecutive patients were studied. All had brain and carotid imaging. Polymerase
      chain reaction-single-stranded conformational polymorphism analysis was used to
      screen exons 3, 4, 5, and 6 of the Notch3 gene for mutations and polymorphisms.
      RESULTS: A single mutation in exon 4 (C697T) was identified in a young patient,
      giving an overall carrier frequency of 0.05% (95% CI, 0.0 to 2.0). For patients
      with onset of lacunar stroke at < or =65 years and leukoaraiosis, the yield was
      2.0% (95% CI, 0.4 to 10.9). CONCLUSIONS: Notch3 mutations are rare in patients
      with typical strokes due to cerebral small-vessel disease. In the absence of
      classic features suggestive of CADASIL, screening for Notch3 mutations has a low
      yield.

PMID- 12511776
TI  - Reperfusion differentially induces caspase-3 activation in ischemic core and
      penumbra after stroke in immature brain.
AB  - BACKGROUND AND PURPOSE: Different strategies for neuroprotection of neonatal
      stroke may be required because the developing brain responds differently to
      hypoxia-ischemia than the mature brain. This study was designed to determine the
      role of caspase-dependent injury in the pathophysiology of pure focal cerebral
      ischemia in the immature brain. METHODS: Postnatal day 7 rats were subjected to
      permanent or transient middle cerebral artery (MCA) occlusion. Diffusion-weighted
      MRI was used during occlusion to noninvasively map the evolving ischemic core.
      The time course of caspase-3 activation in ischemic brain tissue was determined
      with the use of an Asp-Glu-Val-Asp-aminomethylcoumarin cleavage assay. The
      anatomy of caspase-3 activation in the ischemic core and penumbra was mapped
      immunohistochemically with an anti-activated caspase-3 antibody in coronal
      sections that matched the imaging planes on diffusion-weighted MRI. RESULTS: A
      marked increase in caspase-3 activity occurred within 24 hours of reperfusion
      after transient MCA occlusion. In contrast, caspase-3 activity remained
      significantly lower within 24 hours of permanent MCA occlusion. Cells with
      activated caspase-3 were prominent in the penumbra beginning at 3 hours after
      reperfusion, while a more delayed but marked caspase-3 activation was observed in
      the ischemic core by 24 hours after reperfusion. CONCLUSIONS: In the neonate,
      caspase-3 activation is likely to contribute substantially to cell death not only
      in the penumbra but also in the core after ischemia with reperfusion.
      Furthermore, persistent perfusion deficits result in less caspase-3 activation
      and appear to favor caspase-independent injury.

PMID- 12511777
TI  - Adventures in the pathophysiology of brain ischemia: penumbra, gene expression,
      neuroprotection: the 2002 Thomas Willis Lecture.
AB  - BACKGROUND: The pathophysiology of cerebral ischemia is well studied in small
      animal models, which offer reproducibility and control of confounding variables
      factors essential to hypothesis-testing. This presentation first highlights
      insights into the ischemic penumbra enabled by a multimodal experimental
      approach; second, discusses gene expression in ischemia; and third, confronts the
      challenges of neuroprotectant therapy. SUMMARY OF REVIEW: The ischemic penumbra:
      Transient (2-hour) middle cerebral artery suture-occlusion in anesthetized rats
      gives rise to highly consistent neurological and histopathological sequelae.
      Autoradiographic local cerebral blood flow (LCBF) studies at 2 hours of occlusion
      define the penumbra as a region of intermediate CBF depression (20% to 40% of
      control) surrounding the densely ischemic core (5% to 20% of control) and
      constituting one half of the entire lesion. Local glucose metabolic rate in the
      acute penumbra is not reduced despite the critical CBF reduction, so that the
      penumbral metabolism/blood flow ratio is markedly elevated. In contrast,
      following 1 hour of recirculation, glucose metabolism throughout the previously
      ischemic hemisphere has become markedly depressed, and the metabolism/flow ratio
      has pseudonormalized. By correlating these data with histopathology using
      multimodal image analysis, the probability of infarction is shown to be highly
      determined by the degree of antecedent CBF reduction. These animal data agree
      strikingly with published results in patients with acute stroke studied by
      positron emission tomography. This remarkable correspondence belies the assertion
      that data from lower species may not be relevant to human stroke. Gene
      expression: Perfusion gradients also determine differential patterns of gene
      expression in ischemia. This can be demonstrated by correlating in situ
      hybridization autoradiographs for gene expression with autoradiographic LCBF data
      and histological infarct maps derived from replicate series. In other studies,
      DNA microarray technology is used to screen for thousands of expressed genes. In
      the 2-hour middle cerebral artery occlusion model with 3-hour recirculation, we
      have identified 28 known ischemia-hypoxia response genes that are upregulated and
      6 that are downregulated, together with 35 upregulated and 41 downregulated genes
      newly connected with ischemia. These findings underscore the enormous complexity
      of ischemic biology and suggest possible novel mechanisms for future exploration.
      NEUROPROTECTION: A desirable neuroprotectant would, in theory, antagonize
      multiple injury mechanisms. We have explored 2 such therapies of particular
      promise. Mild brain hypothermia (32 degrees C target temperature, for 5 hours) is
      highly neuroprotective even when initiated at the onset of recirculation. Another
      highly protective agent is human albumin, administered in doses of 1.25 to 2.5
      g/kg--a therapy that reduces infarct volume in this ischemia model by 60% to 65%,
      markedly diminishes brain swelling, and has a therapeutic window extending to 4
      hours. CONCLUSION: The careful study of rodent ischemia models can yield
      valuable, clinically relevant insights into the pathophysiology of ischemic
      stroke.

PMID- 12511778
TI  - Ultra-early hemostatic therapy for intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) causes higher morbidity and mortality
      than other forms of stroke and has no proven effective treatment. Hematoma volume
      is a powerful predictor of outcome after ICH. SUMMARY OF REVIEW: Historically,
      ICH bleeding was considered to be a monophasic event that stopped quickly as a
      result of clotting and tamponade by surrounding brain tissue. More recently,
      prospective and retrospective CT-based studies have demonstrated that hematoma
      growth occurs in up to 38% of patients initially scanned within 3 hours of onset
      and in 16% scanned between 3 and 6 hours, even in the absence of coagulopathy.
      Progressive bleeding of this type has been associated with contrast extravasation
      on CT angiography and poor outcome after early (<4 hours) surgical clot
      evacuation. On the basis of these observations, it is plausible that ultra-early
      hemostatic therapy given in the emergency setting might reduce ICH volume in some
      patients and improve outcome. Among candidate agents for this indication, the
      most promising is recombinant activated factor VIIa, which promotes local
      hemostasis at sites of vascular injury in both coagulopathic and normal patients.
      CONCLUSIONS: Ultra-early hemostatic therapy, given within 3 to 4 hours of onset,
      may potentially arrest ongoing bleeding and minimize hematoma growth after ICH.
      Given the current lack of effective therapy for ICH, clinical trials testing this
      treatment approach are justified.

PMID- 12511779
TI  - Resolved: Heparin may be useful in selected patients with brain ischemia.

PMID- 12511780
TI  - Full heparin anticoagulation should not be used in acute ischemic stroke.

PMID- 12511781
TI  - Heparin in stroke: not for most, but the controversy lingers.

PMID- 12511782
TI  - Oral anticoagulants versus antiplatelet therapy for preventing further vascular
      events after transient ischemic attack or minor stroke of presumed arterial
      origin.

PMID- 12511783
TI  - Introductory overview: X-ray absorption spectroscopy and structural genomics.
AB  - A special Issue of the Journal is presented, dedicated to biological applications
      of X-ray absorption spectroscopy (BioXAS) and examining the role of this
      technique in post-genomic biology. The Issue confirms that BioXAS has come of age
      and it can be expected to make a significant contribution in the structural
      genomics effort on metalloproteins, which are estimated to make up about 30% of
      proteins coded by genomes.

PMID- 12511784
TI  - A structural genomics initiative on yeast proteins.
AB  - A canonical structural genomics programme is being conducted at the Paris-Sud
      campus area on baker's yeast proteins. Experimental strategies, first results and
      identified bottlenecks are presented. The actual or potential contributions to
      the structural genomics of several experimental structure-determination methods
      are discussed.

PMID- 12511785
TI  - Marriage of XAFS and crystallography for structure-function studies of
      metalloproteins.
AB  - Metalloproteins constitute a significant proportion of all known genomes. In this
      Article it is shown that the marriage of two synchrotron-radiation-based
      structural techniques, namely high-resolution crystallography and XAFS, can yield
      unprecedented levels of structural information that is directly relevant to the
      mechanism/function of these important macromolecules.

PMID- 12511786
TI  - Experimental aspects of biological X-ray absorption spectroscopy.
AB  - Spectroscopic techniques, like X-ray absorption spectroscopy, will provide
      important input for integrated biological projects in genomics and proteomics.
      This contribution summarizes technical requirements and typical set-ups for both
      simple and complex biological XAS experiments. An overview on different
      strategies for sample preparation is discussed in detail. Present and future
      BioXAS spectrometers are presented to help potential users in locating the
      spectrometer required for their biological application.

PMID- 12511787
TI  - An overview of the CCP4 project in protein crystallography: an example of a
      collaborative project.
AB  - The Collaborative Computational Project Number 4 (CCP4) was established in 1979
      to promote collaboration between UK groups writing software for protein
      crystallography. CCP4 now distributes a large software suite and is active in
      developing new software. Equally importantly, CCP4 provides a focus for the whole
      protein crystallography community via meetings, workshops, email lists and
      various publications. In this Article, an overview is given of CCP4 activities
      and their administration. The emphasis is on generic features of the
      collaboration rather than details specific to protein crystallography. The CCP4
      model has inspired similar developments in NMR, and it is hoped that the
      biological XAS community may pursue similar collaboration.

PMID- 12511788
TI  - X-ray absorption spectroscopy: state-of-the-art analysis.
AB  - State-of-the-art techniques for analysing X-ray absorption spectra are reviewed,
      with an eye to biological applications. Recent attempts to perform full spectral
      fitting of the XANES energy region and beyond for the purpose of structural
      analysis have met with encouraging success. The present paper analyses the
      theoretical motivations behind this success and indicates routes for future
      improvements. The theoretical background is not entirely new, although the point
      of view is, and some sections and appendices present material that the Authors
      believe has never been published before. The aim of this paper is to provide a
      theoretical analysis that is as self-contained as possible.

PMID- 12511789
TI  - New developments in the theory and interpretation of X-ray spectra based on fast
      parallel calculations.
AB  - There has been dramatic progress over the past decade both in theory and in ab
      initio calculations of X-ray absorption fine structure. Significant progress has
      also been made in understanding X-ray absorption near-edge structure (XANES).
      This contribution briefly reviews the developments in this field leading up to
      the current state. One of the key advances has been the development of several ab
      initio codes such as FEFF, which permit an interpretation of the spectra in terms
      of geometrical and electronic properties of a material. Despite this progress,
      XANES calculations have remained challenging both to compute and to interpret.
      However, recent advances based on parallel Lanczos multiple-scattering algorithms
      have led to speed increases of typically two orders of magnitude, making fast
      calculations practicable. Improvements in the interpretation of near-edge
      structure have also been made. It is suggested that these developments can be
      advantageous in structural biology, e.g. in post-genomics studies of
      metalloproteins.

PMID- 12511790
TI  - Local structure in molecular complexes probed by multiple-scattering XAS.
AB  - The GNXAS (n-body distribution function X-ray absorption spectroscopy) method for
      multiple-scattering (MS) data analysis of EXAFS (extended X-ray absorption fine
      structure) data and the results recently obtained on molecular complexes relevant
      to biological matter are briefly reviewed and discussed. Practical MS
      calculations for important molecular fragments like Fe-O-O and Fe-C-N-Cu are
      presented in detail showing the potential of the techniques for measuring bond
      angle distributions. The optimal conditions for obtaining accurate structural
      refinements using EXAFS measurements and modern data-analysis schemes are
      discussed as well as the current perspectives in the exploitation of the
      technique.

PMID- 12511791
TI  - The MXAN procedure: a new method for analysing the XANES spectra of
      metalloproteins to obtain structural quantitative information.
AB  - The first quantitative analyses are reported of the Fe K-edge polarized X-ray
      absorption near-edge structure (XANES) of a single crystal of the iron protein
      carbonmonoxy-myoglobin (MbCO) and of its cryogenic photoproduct Mb*CO. The CO-Fe
      heme local structure has been determined using a novel fitting procedure, named
      MXAN, which is able to fit the XANES part (from the edge to about 200 eV) of
      experimental X-ray absorption data. This method is based on the comparison
      between the experimental spectrum and several theoretical spectra that are
      generated by changing the relevant geometrical parameters of the site around the
      absorbing atom. The theoretical spectra are derived in the framework of the full
      multiple-scattering approach. The MXAN procedure is able to recover information
      about the symmetry and atomic distances, and the solution is found to be
      independent of the starting conditions. The extracted local structure of Mb*CO
      includes an Fe-CO distance of 3.08 (7) A, with a tilting angle between the heme
      normal and the Fe-C vector of 37 (7) degrees and a bending angle between the Fe-C
      vector and the C-O bond of 31 (5) degrees

PMID- 12511792
TI  - Calculating X-ray absorption near-edge structure at very low energy.
AB  - The measurement and calculation of X-ray absorption near-edge structure at very
      low energy can provide important information about a metallic center in
      biological compounds. A rapid overview of the biological applications of this
      technique is given, then a new method of calculating the spectra is presented.
      This technique, based on the use of the finite-difference method to solve the
      Schrodinger equation, is especially precise and potentially applicable to
      metalloproteins. Examples of its use on an oxide and an organic compound
      illustrate the kind of spectroscopic information that can be obtained.

PMID- 12511793
TI  - Simulating the XANES of metalloenzymes - a case study.
AB  - The analysis of XANES patterns is very indicative for screening samples. Powerful
      X-ray absorption spectroscopy data-analysis programs can simulate these patterns.
      Here, a case study on two structural motifs is presented: a non-heme Fe site (2
      His-1-carboxylate motif) and the metallo beta-lactamase dinuclear Zn site.
      Simulations of the edge shapes for different structural models will be compared
      with experimental results, pointing out limitations and challenges. The influence
      of single neighbouring atoms in the first and second shell on the resulting XANES
      pattern is discussed. Insights into catalytic mechanisms and the requirements for
      future theory development are addressed.

PMID- 12511794
TI  - XAS of dilute biological samples.
AB  - The experimental setup of beamline ID26 at ESRF (Grenoble) has been successfully
      exploited to obtain high-quality XAS (X-ray absorption spectroscopy) data from a
      biological sample where the metal concentration is about 100 micro M. The sample
      consists of the adenosine monophosphate deaminase (AMPD) histidine proline rich
      glycoprotein (HPRG) complex that contains 3-4 Zn(II) ions per dimer of
      approximately 320 kDa molecular weight. The experiment shows that third
      generation X-ray sources equipped with insertion devices and appropriate optics
      and detectors allow the investigation of complex biological systems where the
      metal concentration is intrinsically low. The availability of such experimental
      setups makes possible a completely new set of experiments in biological XAS.

PMID- 12511795
TI  - XAFS studies of nitrogenase: the MoFe and VFe proteins and the use of
      crystallographic coordinates in three-dimensional EXAFS data analysis.
AB  - This paper reports a three-dimensional EXAFS refinement of the Mo coordination
      sphere of the FeMoco cluster of the dithionite-reduced MoFe protein from
      Klebsiella pneumoniae nitrogenase (Kp1) using the 1.6 A-resolution
      crystallographic coordinates. At this resolution, the positions of the heavy (Fe
      and S) atoms of the cluster are well determined and there is excellent agreement
      between the crystallographic and EXAFS models. However, the lighter homocitrate
      and histidine ligands are poorly determined in the crystal structure, and it is
      shown that the application of EXAFS-derived distance restraints during the early
      stages of crystallographic refinement provides a means of substantially improving
      (by approximately 0.1 A) the final crystallographic model. The consistency of the
      EXAFS analysis with the crystallographic information in this case justifies
      applications of EXAFS to cases where protein crystal structures are absent. Thus,
      the VFe protein of V-nitrogenase has been shown by EXAFS to possess a V-atom site
      catalytically similar to the well characterized MoFe-nitrogenases, with V
      replacing Mo.

PMID- 12511796
TI  - X-ray absorption spectroscopy to watch catalysis by metalloenzymes: status and
      perspectives discussed for the water-splitting manganese complex of
      photosynthesis.
AB  - Understanding structure-function relations is one of the main interests in the
      molecular biosciences. X-ray absorption spectroscopy of biological samples
      (BioXAS) has gained the status of a useful tool for characterization of the
      structure of protein-bound metal centers with respect to the electronic structure
      (oxidation states, orbital occupancies) and atomic structure (arrangement of
      ligand atoms). Owing to progress in the performance characteristics of
      synchrotron radiation sources and of experimental stations dedicated to the study
      of (ultra-dilute) biological samples, it is now possible to carry out new types
      of BioXAS experiments, which have been impracticable in the past. Of particular
      interest are approaches to follow biological catalysis at metal sites by
      characterization of functionally relevant structural changes. In this Article,
      the first steps towards the use of BioXAS to 'watch' biological catalysis are
      reviewed for the water-splitting reactions occurring at the manganese complex of
      photosynthesis. The following aspects are considered: the role of BioXAS in life
      sciences; methodological aspects of BioXAS; catalysis at the Mn complex of
      photosynthesis; combination of EXAFS and crystallographic information; the freeze
      quench technique to capture semi-stable states; time-resolved BioXAS using a
      freeze-quench approach; room-temperature experiments and 'real-time' BioXAS;
      tasks and perspectives.

PMID- 12511797
TI  - X-ray absorption spectroscopic studies of zinc in the N-terminal domain of HIV-2
      integrase and model compounds.
AB  - X-ray absorption spectroscopy (XAS), including extended X-ray absorption fine
      structure (EXAFS) and X-ray absorption near-edge structure (XANES) analysis, has
      been carried out at the Zn K edge of the N-terminal part of the integrase protein
      of the human immunodeficiency virus, type 2 (HIV-2), and of some zinc
      coordination compounds. In the presence of excess beta-mercaptoethanol, which was
      present in the NMR structure elucidation of the protein [Eijkelenboom et al.
      (1997), Curr. Biol. 7, 739-746; (2000), J. Biomol. NMR, 18, 119-28], the protein
      spectrum was nearly identical to that recorded in its absence. Comparison of the
      XANES of the protein with that of model compounds and literature data permits the
      conclusion that the Zn ion is four-coordinated. The major shell of the EXAFS
      provides evidence for a mixed (N or O as well as S) coordination sphere, while
      the minor shells indicate imidazole coordination. Our approach to the analysis of
      the EXAFS, including quantification of the imidazole by multiple scattering
      simulations with EXCURV92, was validated on the model compounds. An important
      result is that with multiple scattering simulations using restraints on the
      parameters of the imidazole rings the number of imidazoles and their orientation
      could be determined. The integrase spectra can be fitted with two sulfur ligands
      at 2.26 A (Debye-Waller-type factor 0.009 A(2)) and two imidazole ligands with
      the N atoms at 1.99 A (Debye-Waller-type factor 0.005 A(2)). The XAS-derived
      geometry is fully consistent with that found in the NMR structure determination
      and, allowing for the Volume contraction due to the temperature difference
      between the experiments, justifies the restraints applied in the structure
      calculation (Zn-S and Zn-N distances of 2.3 A and 2.0 A, respectively).

PMID- 12511798
TI  - X-ray absorption spectroscopy of low-molar-mass metallic complexes in pharmacy.
AB  - X-ray absorption spectroscopy provides valuable information on metallic
      speciation and so has a wide range of applications in bioinorganic systems. In
      this paper, low-molar-mass metallic complexes as used in pharmaceutical science
      are focused on. The results of structural studies on metal-based drugs applied as
      disease treatments, nutritional supplements or tools for diagnostic methods are
      presented. Then metal speciation (spatial and chemical distribution) in
      biological samples through micro-XANES imaging experiments are dealt with.
      Problems arising from the analysis of noisy data collected from these diluted
      samples are discussed.

PMID- 12511802
TI  - Brief Intervention in Hazardous Drinking: An Important Adjunct to Medical School
      ATOD Curriculum.
AB  - Most medical school alcohol, tobacco and other drug (ATOD) curricula emphasize
      the diagnosis and treatment of alcohol abuse and dependence, even though a
      significant amount of alcohol-related morbidity and mortality is associated with
      the hazardous use of alcohol. An increased emphasis on screening for hazardous
      drinking and the use of early intervention has been shown to be effective in
      reducing heavy drinking in the primary care setting. This paper describes a
      family medicine clerkship seminar on clinical preventive medicine that focuses on
      tobacco and alcohol use. Results indicate that students learn that brief
      intervention counseling can influence patient behavior and plan to continue to
      use it in future patient encounters. However, the low number of students electing
      to intervene in hazardous drinking suggests that more curricular time is needed
      to overcome student resistance to addressing the alcohol use patterns of their
      patients.

PMID- 12511803
TI  - Substance Abuse in Hawaii: Perspectives of Key Local Human Service Organizations.
AB  - Available evidence suggests that substance abuse in Hawaii is a substantial
      problem. The three major objectives of this study were to determine qualitatively
      Hawaii's human service organizations' perspective regarding (1) the magnitude of
      the statewide substance abuse problem, (2) the unmet needs of the state's
      substance abuse treatment system, and (3) the features of the problem unique to
      Hawaii's many ethnic and other subgroups. The study targeted those human service
      organizations most burdened by the substance abuse problem. Respondents from 55
      human service organizations were interviewed using a series of 21 open-ended
      questions. Respondents perceived the magnitude of the Hawaii substance abuse
      problem to be at least comparable to that of the mainland United States. Although
      most respondents viewed the problem using a medical model, the problem was
      generally thought to be exacerbated by a community context in which substance
      abuse is accepted, excused, or denied. Increasing use of crystal methamphetamine
      and heroin were cited as the most worrisome trends. Systems issues identified
      were unstable funding, insufficient detoxification services, and limited
      availability of residential treatment and supportive services following
      treatment, such as housing and aftercare. Service delivery problems frequently
      associated with rural areas were identified, such as transportation, staff
      development, outreach, and difficulty providing a full range of services,
      particularly on neighbor islands. Cultural alienation, exacerbated by the state's
      prevailing multiculturalism, was thought to contribute to the substance abuse
      problem among all ethnic groups, but especially among Native Hawaiians. Cultural
      factors were thought to have a major impact on seeking care and subsequent
      acceptance of such care. Further study is needed to understand better the content
      of care, therapeutic elements, and efficacy of culturally specific treatment and
      prevention programs. To initiate change, concerted efforts are needed to inform
      Hawaii residents about the statewide substance abuse problem and local treatment
      system needs. Future studies should compare human service organization
      perceptions to those of individuals abusing substances and using these services.

PMID- 12511804
TI  - Reducing Bias in Observational Research on Alcohol Withdrawal Syndrome.
AB  - Observational methods are often used to study alcohol withdrawal syndrome.
      Observational cohorts and case-control studies are useful in research on
      prognosis and in situations where ethical concerns might prevent the use of
      clinical trial designs. In addition, case-control studies are appropriate for
      studying the rare but serious complications of alcohol withdrawal syndrome.
      Despite their appeal and suitability, these methods are subject to a number of
      biases that can render their results suspect. Susceptibility, diagnostic
      suspicion, and exposure suspicion bias are among the important biases to consider
      in observational studies on alcohol withdrawal syndrome. Strategies for reducing
      these biases include the creation of inception cohorts, the use of operational
      definitions, and blinding. Increased attention to these strategies should help
      clinicians and researchers improve the practice of caring for patients with
      alcohol withdrawal syndrome.

PMID- 12511805
TI  - Aftercare Compliance: Perceptions of People with Dual Diagnoses.
AB  - This descriptive study was designed to learn, from the perspective of dually
      diagnosed inpatients, what factors affect their maintenance of an aftercare
      program. Ten audio-recorded focus groups were conducted using a structured
      interview schedule; additionally, patients participated in structured brief
      individual interviews, and their medical records were reviewed for demographic
      data and chief complaints on admission. Despite the numerous obstacles
      encountered by this population intrapersonally, interpersonally, environmentally,
      and socially, participants were able to provide (a) specific information to
      increase the understanding of compliance from their perspective and (b)
      recommendations for health care professionals to facilitate adherence to
      aftercare treatment plans.

PMID- 12511806
TI  - Predictors of Attrition from an Outpatient Chemical Dependency Program.
AB  - This study investigated differences between completers and noncompleters of an
      intensive outpatient substance abuse treatment program to identify key predictors
      of attrition. Participants (n = 138) completed a comprehensive intake/assessment
      package that included the Addiction Severity Index as a precursor to
      participation in the program. Discriminant function analyses (DFA) suggested that
      ASI composite scores and severity ratings were not useful predictors. However,
      analysis of individual items was useful in identifying "red flags" as predictors
      for treatment attrition. The subsequent DFA identified the following variables as
      significant predictors: Hispanic ethnicity, absence of a professional skill,
      shorter time since last hospitalization, cocaine or cannabis use in the last 30
      days, total number of family members with drug problems, presence of emotional
      abuse in last 30 days, concern with family problems, and number of family group
      meetings that family members attended. These red flags can serve the important
      function of providing clinicians with enough information to intervene early with
      patients at risk for treatment dropout.

PMID- 12511807
TI  - Temperament Style and Substance Abuse Characteristics.
AB  - The relationship of temperament to different patterns and types of alcohol abuse
      has received much attention over the last decade in order to provide clues to
      matching patients optimally to treatment strategies. The purpose of this study
      was to examine the relationship of temperament with a number of relevant
      substance abuse characteristics in a substance abusing population. One hundred
      forty-five male veterans were interviewed on their lifetime use of substances and
      on their psychiatric symptoms, problems associated with use, context, and family
      history of substance abuse. Subjects filled out the TPQ and the MPQ, which were
      subjected to factor analysis and revealed four factors: (1) Negative
      Affectivity/Impulsivity, (2) Positive Affectivity/Sociability, (3)
      Persistence/Achievement, and (4) Constraint. There was partial support for the
      hypotheses. Impulsivity was negatively correlated with age of onset and
      positively correlated with substance-related problems and a family history of
      substance abuse. Subjects with a history of depression scored significantly lower
      on the Positive Affectivity/Sociability factor than those who had not experienced
      a significant depression. Individuals who used alone scored lower on this factor
      than those who used in social contexts. The temperament factors of
      Persistence/Achievement and Constraint were, for the most part, unrelated to
      substance abuse.

PMID- 12511808
TI  - The Natural History of Smoking Cessation Among Medical Patients in a Smoke-Free
      Hospital.
AB  - Our purpose was to determine the frequency and predictors of quitting smoking
      among patients hospitalized on the medical services of a smoke-free hospital. All
      smokers admitted to the medical services of a single university teaching hospital
      were eligible and 129 patients were enrolled. A questionnaire detailing
      demographic information, stages of change, smoking behavior while hospitalized,
      and intention to remain abstinent on discharge was administered. The primary
      discharge diagnosis was obtained from the medical record. Patients were followed
      at 3- and 6-month intervals for continuous abstinence, with expired carbon
      monoxide confirmation at 6 months. A total of 7% of smoking patients receiving
      usual medical care were continuously abstinent at 6 months. Of those who
      relapsed, 45% did so by the time of discharge, 18% within the first week, 20%
      between 1 week and 3 months, and 10% between 3 and 6 months after discharge. All
      patients who were abstinent at 6 months had been admitted for coronary artery
      disease (CAD). Nine of the 38 patients with CAD were abstinent, versus none of 93
      with another diagnosis (p <.001). Smokers admitted to a smoke-free hospital had a
      high rate of relapse, especially early after discharge. Patients admitted for CAD
      had a greater likelihood of successfully quitting. Designing hospital-based
      smoking cessation interventions with a focus on early relapse prevention may help
      improve smoking cessation rates.

PMID- 12511809
TI  - Stage of Change as a Predictor of Abstinence Among Alcohol-Dependent Subjects in
      Pharmacotherapy Trials.
AB  - In order to evaluate the stages of change model as a predictor of abstinence
      among alcoholics, we examined abstinence rates at the end of treatment and at a 6
      month posttreatment follow-up in 113 alcohol-dependent subjects participating in
      two 12-week, placebo-controlled pharmacotherapy trials. Hierarchical logistic
      regression was used to examine the predictive validity of stages of change
      variables. At the end of treatment and at follow-up, individuals with a higher
      predisposition toward action were more likely to be abstinent. Subjects who
      received an active medication (buspirone or fluoxetine) were more likely also to
      remain abstinent during the 6-month posttreatment follow-up. Scores on measures
      of precontemplation, contemplation, and maintenance failed to predict abstinence
      either at the end of treatment or at follow-up. Although none of the stages of
      change measures were associated with treatment completion, married or cohabiting
      individuals were more likely to complete treatment. Despite that scores on the
      precontemplation, contemplation, and maintenance subscales were not associated
      with abstinence, a measure of readiness for action contributed significantly to
      the prediction model.

PMID- 12511810
TI  - Differences in Perimenstrual Symptoms Between Cocaine-Abusing and Non-Cocaine
      Abusing Women.
AB  - Cocaine abuse among women has become a major health problem in the United States,
      yet there is little information in the literature concerning the effects of this
      form of substance abuse on a woman's reproductive system. This study of 65 women
      in residential treatment for cocaine abuse and 65 non-cocaine-abusing women was
      undertaken to determine if there are differences in frequency or severity of
      perimenstrual symptoms between these two groups of women. Data were collected by
      questionnaire and included demographics, a substance use history, and the
      Menstrual Distress Questionnaire developed by Moos. Findings suggested that there
      are statistically significant differences in frequency and severity of
      perimenstrual symptoms between the two groups of women.

PMID- 12511811
TI  - Drugnet: A Pilot Study of Adult Recreational Drug Use via the WWW.
AB  - This study was intended (1) to explore the potential of using the World Wide Web
      (WWW) of the Internet to sample hidden populations and (2) to collect exploratory
      data on the hidden population of nonabusive, recreational users of illicit drugs.
      The survey modules were designed to assess demographics and lifestyle, drug
      experiences (including absence of DSM-IV criteria for abuse or dependence), legal
      history (drug-related arrests, etc.), and mental health as measured by the
      General Well-Being Schedule (GWBS). The survey was completed by 276 persons, aged
      18 to 62, with a mean age of 32.34. The sample was predominantly white (93%),
      male (78%), college educated (75%), and employed full-time (76%). The WWW is a
      useful tool for reaching hidden populations but is likely to impose a bias toward
      male, better educated, and more computer-involved samples on the respondents
      reached. This survey further documents the existence of a nonclinical population
      of drug users which is generally healthy, well-adjusted, and productive.

PMID- 12511812
TI  - The Effect of Postdetoxification Drug-Free Residential Living on Birth Outcome in
      the Pregnant Drug Abuser.
AB  - The birth outcome for pregnant drug abusers is complicated by polydrug use,
      neonatal withdrawal symptoms, and low birth weight. To improve birth outcome, in
      hospital detoxification and stabilization from drug use followed by drug-free
      residential living with prenatal care were provided for patients committed to
      cessation of illicit drug use. Pregnant heroin or cocaine abusers with
      significant drug use were eligible for the study. The birth outcome for the 30
      term singletons born to the mothers in the program was statistically compared
      with respect to low birth weight, mean birth weight and length of stay in the
      nursery to that for 44 term singleton infants of a similar group of drug-abusing
      ambulatory pregnant women in our aftercare clinic, not in the residential
      program. Twenty percent of 152 patients evaluated were found suitable for
      admission to the program. Numerical data for term singletons were as follows:
      weights (g +/- SD), 3218 +/- 596 (30) vs control 2806 +/- 317 (44); low birth
      weights; 1/30 vs control 12/44; and length of stay in the nursery (days +/- SD),
      3 +/- 0.5 (30) vs control 5.5 +/- 2.5 (44). For the pregnant drug abuser
      committed to cessation of drug use, detoxification followed by drug free living
      leads to a statistically significant improvement in birth outcome.

PMID- 12511813
TI  - Change in Alcohol Effect and Self-Efficacy Expectancies During Addiction
      Treatment.
AB  - Alcohol effect expectancies and situational self-efficacy are important factors
      in addiction relapse. The extent to which these cognitive factors change during
      alcohol treatment and the relations between change in these two domains may
      facilitate our understanding of the transition out of addictive lifestyles. To
      evaluate such change, 101 male and female participants in an abstinence focused
      inpatient alcohol and drug treatment program completed measures of alcohol effect
      expectancies (AEQ) and self-efficacy (SCQ) during the first and fourth (final)
      week of inpatient treatment. Analyses confirmed our predictions that alcohol
      effect expectancies and self-efficacy were inversely correlated at the beginning
      of treatment, and that both alcohol expectancies and self-efficacy changed
      significantly during the four-week treatment program. Larger decreases in alcohol
      effect expectancies were evident for individuals who entered treatment with less
      confidence in their ability to resist drinking compared to those with more
      confidence in potential drinking situations. Results suggest that both
      expectancies and self-efficacy are useful factors to target in alcohol treatment.

PMID- 12511814
TI  - Schizophrenic Patients and Cocaine Use: Antecedents to Hospitalization and Course
      of Treatment.
AB  - This study was designed to assess whether cocaine abuse was associated with a
      different set of antecedents and course for hospitalized schizophrenic patients.
      Forty-three cocaine-using and 27 non-cocaine-using patients with schizophrenia
      admitted to a dual diagnosis unit were compared with regard to antecedents to
      hospitalization such as prior treatment episodes, reliance on drugs for pleasure
      and tension reduction, and criminal history as well as course of hospital
      treatment. Cocaine-using patients were more likely to have had a history of prior
      inpatient drug treatment and to rely on drugs to a greater extent for tension
      reduction and pleasure. There was a trend for cocaine users to have a history of
      arrests for violent crimes. Although cocaine-using patients exhibited lower
      levels of global distress during the first week of hospitalization, they were no
      different from their counterparts who abused nonpsychostimulant drugs with regard
      to outcome of hospital treatment. These findings suggest that the lifetime course
      of illness among schizophrenic patients presenting for hospitalization who abuse
      cocaine may be characterized by episodes of repeated inpatient drug treatment and
      impaired impulse control. More rigorous discharge planning and aftercare program
      monitoring in the community as well as stress management interventions directed
      to tension reduction are therefore warranted.

PMID- 12511815
TI  - Reliability of Form 90D: An Instrument for Quantifying Drug Use.
AB  - Clients just entering treatment for nonalcohol primary drug use were asked to
      report on their frequency of drug use at two times 2 days apart. Test-retest
      correlations for the lifetime use of drugs were fair to excellent, and those for
      drug use in the last 90 days, although variable, were generally very good. For
      lifetime use, correlations were highest for opiates and stimulants and lowest for
      inhalants, whereas for the recent period correlations were highest for opiates
      and lowest for stimulants. Correlations were uniformly high for measures of
      general life functioning. Initial validity assessments with urine drug screen
      results as criterion were good, with no false negative errors in four of six drug
      use categories. Overall Form 90D appears to be a reasonably reliable and valid
      interview instrument for measuring drug use occurrence and frequency for both
      lifetime and recent use. Care is warranted in assessing classes of drugs that are
      used less frequently.

PMID- 12511816
TI  - Comparison of Three Methods to Assess Binge Consumption: One-Week Retrospective
      Drinking Diary, AUDIT, and Quantity/Frequency.
AB  - Binge consumption contributes substantially to the occurrence of alcohol-related
      harm. Despite its importance, binge drinking is not well defined in the
      literature. The present study examines the proportions of respondents identified
      as binge drinkers by three separate measures: a 1-week retrospective drinking
      diary (RD), the Alcohol Use Disorders Identification Test (AUDIT), and a
      quantity/frequency (QF) question. Overall, AUDIT detected the highest proportion
      of binge drinkers, followed by QF and RD. There was also good agreement between
      QF and RD, as well as QF and AUDIT. Ultimately, the measure of choice should be
      that which provides information most appropriate to the purposes of each study.

PMID- 12511817
TI  - Integrating Substance Abuse Content into Social Work Courses: Effects of
      Intensive Faculty Training.
AB  - An evaluation was conducted in a graduate school of social work to assess the
      integration of substance abuse content into basic and advanced courses by
      instructors with and without specialized substance abuse training. Students in
      these courses completed questionnaires that asked about the amount, type, and
      usefulness of substance abuse content presented during the semester. Instructors
      with and without specialized substance abuse training completed questionnaires
      that examined their perceptions of the amount, type, and usefulness of the
      substance abuse content they had taught. Results showed that (1) faculty with
      specialized substance abuse training were more likely than faculty without such
      training to integrate substance abuse content; (2) courses taught by trained
      faculty received higher ratings from students on the quality of the content; (3)
      both groups of faculty (trained and untrained) perceived that more substance
      abuse content had been taught than their students perceived; and (4) neither
      faculty nor students perceived that too much substance abuse content had been
      taught. This approach could be useful to social work programs and other
      disciplines interested in measuring the effects of changes in course content.

PMID- 12511818
TI  - Perinatal Substance Abuse Education: A Review of Existing Curricula.
AB  - The magnitude of the substance abuse problem in this country requires that health
      care professionals be appropriately and adequately trained to recognize and care
      for substance abusing patients, yet didactic and clinical curricular content on
      the topic remains limited for most of them. Efforts have been made over the past
      25 years to develop faculty who have expertise in alcohol, tobacco, and other
      drug abuse and who can provide leadership in curricular development. Through
      these efforts, pockets of faculty expertise developed in nursing, medicine,
      social work, and psychology programs around the country. In addition, a number of
      printed substance abuse curricula were developed. The purpose of this article is
      to address issues regarding the substance abuse information needed by health
      professionals and to review the available educationial curricula, especially as
      they relate to perinatal substance abuse. Discussion of methods to update
      information as substance abuse knowledge expands is also included.

PMID- 12511819
TI  - A Pilot Project: Continuing Education for Pharmacists on Substance Abuse
      Prevention.
AB  - The American Association of Colleges of Pharmacy advocates that pharmacists can
      have a significant impact on substance abuse prevention provided they receive
      adequate training. Continuing education programs are needed to enable practicing
      pharmacists to augment their limited education. This paper examines the process
      the Society of Teachers of Family Medicine (STFM) used to develop a pilot
      continuing education program for pharmacists. With limited literature and a small
      number of pharmacy teaching about substance abuse, input on topics and training
      methods was obtained from a convenience sample of practicing pharmacists to
      enhance the information from the pharmacist faculty regarded as content experts.
      Results of this pilot study revealed lack of agreement between faculty and
      practicing pharmacists regarding the prioritizing of content and educational
      methods. Consequently, input must be obtained from targeted audiences instead of
      relying solely on the advice of identified academic content experts when
      designing continuing educational programs. Other professions should consider this
      process when designing continuing education programs. Pharmacists are poised to
      play an important role in the prevention of substance abuse problems, but they
      need continuing education about substance abuse.

PMID- 12511820
TI  - Evaluation of a Grief Group for Women in Residential Substance Abuse Treatment.
AB  - Most women in substance abuse treatment have experienced significant losses. This
      preliminary study examined the effectiveness of a therapy group addressing grief
      and loss among women enrolled in a gender-specific residential substance abuse
      treatment program. The intervention group consisted of 24 grief group
      participants and the comparison group consisted of 31 nonparticipants.
      Qualitative analysis revealed a pattern: participants identified traumatic loss,
      moved to emotional loss and abandonment by their own mothers, then focused on
      their own children. Data obtained at induction and at exit or follow-up were used
      for quantitative analysis. Length of stay, self-esteem, depression, mood, and
      parenting attitudes were assessed using standardized instruments. Women who
      participated in the grief group remained in treatment longer. While both groups
      were depressed and had low self-esteem at induction, the self-esteem of
      nonparticipants was significantly lower than that of participants. Both groups
      improved over time on mood, depression, and parenting. At exit or follow-up,
      participants had higher self-esteem. Based on these findings, we hypothesized
      that higher self-esteem at induction made it possible for women to participate in
      and benefit from the grief group, thus contributing to length of stay. To test
      this hypothesis we conducted regression analyses which found that, individually,
      group status (participation) and self-esteem explained 11% of the variance in
      length of stay. However, since the number of women with available data varied for
      group status and self-esteem, group status was a significant predictor of length
      of stay and self-esteem showed only a trend toward significance. These findings
      support our hypothesis. The women's pattern of disclosure and the hypotheses
      drawn from the results of this preliminary analysis will be examined further in
      an evaluation of a series of groups focused on loss and grief.

PMID- 12511821
TI  - A Treatment Algorithm for Attention Deficit Hyperactivity Disorder in Cocaine
      Dependent Adults: A One-Year Private Practice Study with Long-Acting Stimulants,
      Fluoxetine, and Bupropion.
AB  - A subgroup of adults in private treatment for cocaine dependence in remission
      reported a therapeutic effect from cocaine during the initial phases of cocaine
      addiction and, also, met DSM-IV criteria for ADHD. We report evidence that study
      subjects probably medicated their ADHD symptoms with cocaine and describe a 1
      year treatment algorithm featuring long-acting stimulants that was effective in
      the management of their ADHD and cocaine dependence. Nineteen stable patients in
      full remission from all substance dependence were entered into an open label,
      prospective, treatment trial for ADHD. The treatment schedule consisted of the
      progressive introduction-and discontinuation of ineffective medication-of each of
      several medications in the following order: fluoxetine, bupropion, pemoline,
      sustained-release methylphenidate, dextroamphetamine spansules, and
      methamphetamine gradumets. Treatment of ADHD was successful. Several treatment
      regimens, especially those including long-acting stimulants, alone or in
      combination with other agents, were highly effective. All but 1 of the 19
      subjects had a fully effective response for at least 1 full year. Mean UTAH scale
      scores were 7.4 before any medications were administered and 1.6 at the end of
      the study. Treatment proved successful in suppressing ADHD symptoms, with minimal
      cocaine slips or side effects.

PMID- 12511822
TI  - The Effects of Salty and Nonsalty Food on Peak Breath Alcohol Concentration and
      Divided Attention Task Performance in Women.
AB  - There is recent evidence that gender-based patterns of alcohol consumption are
      becoming less dissimilar and that, per capita, women are consuming more alcohol
      than ever before. Therefore, a better understanding of the acute effects of
      moderate alcohol consumption in women is essential to establishing reliable
      health and safety educational information. To address one component of health and
      safety information, we sought to determine if peak breath alcohol concentrations
      (BAC) could be manipulated by varying the amount of sodium our women participants
      ingested in a test meal. We also measured the association between BAC and the
      participant's performance on a divided attention (DA) task. The 12 participants
      were trained to use a computer-generated DA task and subsequently participated in
      all of four experimental conditions. During each experimental session the
      participant consumed a placebo drink or a drink containing 0.6 g/kg ethanol and a
      220-kcal portion of salted or unsalted pretzels. She then performed four 15-min
      trials of the DA task, after which the BAC was measured and recorded. Reaction
      times and mean tracking error were recorded for each DA trial. Experimental
      sessions took place at the same time on days 7, 8, 9, and 10 of the participant's
      menstrual cycle. The BAC was significantly higher in the ethanol plus sodium
      condition than in the ethanol with no sodium condition. Reaction times and
      tracking tasks were impaired in all ethanol conditions. Scores on the DA tasks
      obtained from the high-sodium group did not differ significantly from those of
      the low-sodium group. When health care personnel provide drug education for women
      clients, the possible BAC-elevating effects of consuming high-sodium foods while
      drinking alcoholic beverages should be discussed.

PMID- 12511823
TI  - Drinking Patterns and Problems: A Comparison of Primary Care with the Emergency
      Room.
AB  - A comparison is made of drinking patterns and problems of probability samples of
      noninjured patients drawn from the emergency room (ER) (n = 974) versus primary
      care clinics (n = 767) in the same metropolitan community. Those in the primary
      care sample were significantly less likely to report heavier drinking,
      consequences of drinking, alcohol dependence, and ever having treatment for an
      alcohol problem, controlling for demographic differences between the two sites.
      The data suggest that while primary care settings remain an important site for
      early identification and intervention for problem drinking, the ER may hold more
      potential for targeting prevention efforts in an era of reduced resources.

PMID- 12511824
TI  - Changes Over One Semester in Drinking Game Playing and Alcohol Use and Problems
      in a College Student Sample.
AB  - One-hundred ninety-five alcohol-using college students completed a questionnaire
      in early September, at the beginning of the fall semester, then completed a
      follow-up questionnaire in mid-November, near the end of the semester. The
      questionnaires included items on levels of alcohol use, the Eysenck I.7 measure
      of impulsiveness and venturesomeness, alcohol expectancies, perceived norms for
      alcohol use, reasons for drinking, and aspects of drinking game playing. As
      predicted, those students who were 18 years of age and younger, nearly all of
      them 1st-year students, significantly increased their levels of alcohol use
      during their first semester in college. While increases in reasons for drinking
      were significantly predictive of increased alcohol use and problems in first-year
      and older students, increases in expectancies of alcohol effects and in
      frequencies of drinking game playing were significantly predictive of increases
      in alcohol use and problems only for first-year students. The present results
      provide further evidence of the importance of drinking games in the socialization
      of college students into problematic alcohol use.

PMID- 12511825
TI  - Baseline Differences in Social Support Among Treatment-Seeking Alcoholics With
      and Without Social Phobia.
AB  - Differences on demographics and seven measures of social support between matched,
      treatment-seeking alcoholics with and without social phobia (SP and NSP groups,
      respectively) were examined. The groups did not differ on most demographic
      variables, although the SP group (n = 397) had a lower occupational status and
      had fewer years of education (both p's <.01) than the NSP group (n = 397). On
      social support measures, the SP group had less perceived social support from
      friends and had a lower performance on the social behavior role scale than the
      NSP group (both p's <.001). The two groups were unexpectedly more similar than
      different on the measures of interest in this study; however, the differences
      identified are meaningful for treatment planning. It is important to ascertain
      the quantity and sources of social support which are available to these clients
      in order to maximize positive treatment outcomes.

PMID- 12511826
TI  - Current Status of Professional Training in the Addictions.
AB  - Addictions training curricula within traditional graduate and postgraduate
      programs of professional disciplines lag behind those devoted to other disorders.
      After presenting a brief historical overview of addictions training in the United
      States, this paper focuses on current addictions training practices for each of
      the major health care professions, highlighting both recent advancements as well
      as shortcomings, particularly with respect to the ability to disseminate recent
      empirically tested addiction treatments. New psychosocial and pharmacotherapies
      for addictive disorders are then discussed which would be better disseminated
      within training programs with enhanced addictions training components. The paper
      concludes with a discussion of and recommendations for enhancing substance abuse
      training and knowledge dissemination.

PMID- 12511827
TI  - Markers for Patients with Alcohol Problems in an Outpatient General Medicine
      Clinic.
AB  - Our purpose was to determine the correlation among alcohol problems, certain
      health habits, and hypertension in a general internal medicine outpatient
      setting. Two-hundred eighty-seven patients who were undergoing complete
      examinations in a general internal medicine department of a large multispecialty
      clinic were asked to participate in a "lifestyle survey" interview, which
      included questions regarding social history, gastrointestinal complaints,
      anxiety/depression, sexual dysfunction, and the Alcohol Use Disorders
      Identification Test (AUDIT). Charts were screened for documentation of alcohol
      problems and the presence of hypertension. Correlations between alcohol problems
      (defined as an AUDIT score >/=8) and the presence of hypertension were made using
      chi-square tests for categorical variables and the t test for continuous
      variables. Of the 287 patients contacted, 12 refused, 3 were ineligible, and 29
      had incomplete data precluding analysis, yielding a total of 233 patients (81%)
      who were included in the analysis. Sixty percent were female, 76% were white, and
      the mean age was 53 years. The overall prevalence of alcohol problems was 7.3%
      and less than one-quarter of those patients had chart documentation of an alcohol
      problem. Thirty percent of those patients had a diagnosis of hypertension. No
      statistically significant correlation between a positive AUDIT and hypertension
      was found. Failure to use seat belts (P = 0.020), history of smoking (P < 0.001),
      alcohol use within 24 hr of the office visit (P < 0.001), and self-reported
      family history of alcoholism (P = 0.012) were significantly more likely in
      patients with active alcohol problems. There was no difference in somatic
      complaints between patients with and patients without alcohol problems. We
      identified certain health behaviors which served as markers for patients with
      active alcohol problems in an outpatient setting. Physician diagnosis of alcohol
      problems (sensitivity of 24% in this study) may be improved with attention to
      such markers. Despite the known relationship of excess alcohol use and elevations
      in blood pressure, we found no statistically significant correlation between
      these variables in our study. Symptomatic concerns of the patient appear to be
      too nonspecific to distinguish patients with and without alcohol problems.

PMID- 12511828
TI  - Cocaine Addiction: Neurobiology and Related Current Research in Pharmacotherapy.
AB  - In this article, recent research studies in the field of cocaine addiction are
      reviewed, with an eye toward emergent options for treatment innovation.
      Particular attention is paid to the neurobiology and specific neurotransmitter
      and receptor mechanisms involved in cocaine abuse, dependence, and other unique
      phenomena of addiction such as sensitization, craving, compulsive drug use, and
      withdrawal. The vicissitudes in the dopamine theory of brain reward mechanisms,
      dopaminergic effects of cocaine, and emerging roles of GABA, serotonin,
      glutamate, and nitric oxide in cocaine addiction and its sequelae are discussed.
      Neuroanatomic findings elicited with imaging studies using PET and functional MRI
      are summarized. These findings support the role of specific brain regions within
      the dopaminergic system such as the ventral tegmentum and nucleus accumbens in
      the induction of the cocaine "high" and craving, respectively. Research
      approaches to the problem of developing effective pharmacotherapeutic options to
      render cocaine ineffective and modalities under study, such as dopamine uptake
      inhibitors and immunotherapy, are also discussed in the context of a variety of
      practical problems faced by these experimental therapies. Pharmacotherapeutic
      strategies and new directions in this research, such as the adaptive changes of
      the opioid system in cocaine addiction, are reviewed. Potential areas for further
      study are brought forth for further debate and possible clinical evaluation.

PMID- 12511829
TI  - Treating Adolescents with Substance Use Disorders: An Overview of Practice Issues
      and Treatment Outcome.
AB  - The knowledge base and research gaps of the adolescent drug abuse treatment field
      are discussed. In addition to summarizing several challenges faced by clinicians
      treating drug-abusing adolescents, traditional and emerging treatment strategies
      are described. The treatment outcome literature is seen as having several
      weaknesses, including that most studies are limited to descriptive designs. The
      author suggests that the most important research priority for the field is to
      address meaningfully the issue of which treatment approaches work best for which
      types of adolescent drug abusers.

PMID- 12511830
TI  - A Comparison of Medical Symptoms Reported by Cocaine-, Opiate-, and Alcohol
      Dependent Patients.
AB  - Substance abuse is frequently associated with adverse medical consequences. The
      differences in medical symptoms reported by 101 alcohol-, 113 cocaine-, and 107
      opiate-dependent individuals receiving outpatient treatment were studied using a
      134-item questionnaire (MILCOM). Data analysis revealed interesting and
      unexpected findings, with cocaine patients reporting the fewest total symptoms
      among the three groups. Moreover, cocaine patients reported significantly fewer
      CNS and musculoskeletal symptoms compared to both alcohol and opiate patients and
      significantly fewer GI and urinary symptoms than the alcohol but not the opiate
      patients. In addition, there were sex- and race-related differences in the
      pattern of symptoms reported. Women reported significantly more CVS, mood,
      nose/throat, CNS, skin, and GI symptoms than men. Similarly, Caucasians reported
      significantly more mood, CNS, nose/throat, head/neck, musculoskeletal, and GI
      symptoms than African-Americans. The study highlights the influence of drug of
      choice, gender, and race on medical needs of substance-abusing persons.

PMID- 12511831
TI  - Coping Strategies of Alcoholic Women.
AB  - Recent efforts have increased research on alcoholic women. Few studies have
      examined the coping mechanisms characteristic of alcoholic women relative to
      their nonalcoholic controls. Conforming to DSM-IV criteria for alcohol
      dependence, 159 alcoholic women stratified by race (black and white) and age (20
      29, 30-39, and 40-49 years) were compared to 150 nonalcoholic women from a
      variety of public and private inpatient and outpatient treatment facilities
      regarding the types of coping strategies used. Alcoholic women were significantly
      more likely to favor maladaptive styles of coping, while nonalcoholic women
      employed significantly more problem-solving and emotion-based coping strategies.
      Neither race nor age differences significantly influenced the types of coping
      utilized by these women. The profile of coping strategies utilized by the
      alcoholic group is consistent with a poor quality of life and compounding of
      problems.

PMID- 12511832
TI  - The Use of Required Treatment for Substance Abusers.
AB  - Studies show that typically less than 10% of alcohol and other drug abusers
      voluntarily enter treatment for their substance abuse, and once in treatment,
      drop out rates are high. One controversial way to get clients into, and to
      participate in, treatment is the use of legally encouraged or required treatment.
      Grounded in the parents patriae doctrine of state protection, the primary
      rationale for required treatment is that some substance abusers require external
      pressure to enter and remain in treatment. The history of required treatment for
      alcohol and other substance abuse, the primary issues surrounding its use, the
      use of required treatment in the criminal justice system, the primary treatment
      models for alcohol and other substance abuse, ways to increase internal and
      external motivation for treatment, and therapist and treatment personnel
      responsibilities in using required treatment are discussed.

PMID- 12511833
TI  - Test-Retest Reliability of the Computerized CIDI (CIDI-Auto): Substance Abuse
      Modules.
AB  - This paper discusses the reliability of the Alcohol and Substance Abuse modules
      of the CIDI-Auto in two countries, Australia and Puerto Rico, and two languages,
      English and Spanish. CIDI-Auto is a computer-assisted version of the CIDI.
      Reliability estimates for DSM/ICD are presented at the diagnostic and symptom
      level. In total, 286 subjects, ages 17-60 years, who had at least 12 drinks of
      alcohol in their lifetime participated in the study. Adequate to good test-retest
      reliability estimates were obtained, with no major differences by nosology, site,
      substance, or time. Harmful use/abuse showed lower kappas than dependence.
      Reliability estimates for dependence ranged from 0.70 to 0.95. For harmful use,
      kappa's ranged from 0.45 to 0.66. The findings are encouraging; CIDI-Auto
      produces reliable classification across two settings and in two languages with an
      instrument that has good coverage of different manifestations of the illness.

PMID- 12511834
TI  - [DepiSCAN: a new method to evaluate lung cancer screening].

PMID- 12511835
TI  - [Screening for bronchial carcinoma].
AB  - Bronchial carcinoma is the principal cause of cancer death. Unlike cancers of the
      breast and colon that are already the subject of screening programmes, proof has
      not yet been provided that screening for bronchial carcinoma is of value in terms
      of reduction in mortality. Technological improvements and the advent of low dose
      spiral CT scanning has lead to a recent renewal of interest in this subject. The
      first preliminary studies seem to indicate that 2/3 of bronchial carcinomas
      discovered by CT scanning are detected at an early stage. Other data suggest a
      possible improvement in survival of tumours discovered by screening. Nevertheless
      it is necessary to demonstrate that screening improves the survival of patients
      with bronchial carcinoma. The present consensus does not advocate mass screening
      by CT scanning but that high risk subjects should voluntarily participate in
      randomised controlled trials which alone will confirm or refute the validity of
      this approach.

PMID- 12511836
TI  - [Management strategy of pulmonary nodules].
AB  - Today pulmonary nodules are commonly detected by spiral CT but their evaluation
      and management remain a difficult task. The traditional approach, based on the
      principles of decision analysis, relies on estimating the probability of
      malignancy from risks factors assessed by history and morphological
      characteristics on chest radiographs and CT examinations. Use of non-invasive
      techniques such as PET and contrast-enhanced CT may decrease the number of
      invasive procedures performed to obtain an histological diagnosis. A precise
      evaluation of nodule growth can be obtained from recent improvements in CT
      technology and may shorten the follow-up. The goal of this review, based on the
      consensus obtained in a multidisciplinary group, is to emphasize the recent
      advances on the topic and to propose guidelines.

PMID- 12511837
TI  - [Vesicoureteric reflux and functional voiding dysfunction in children].
AB  - PURPOSE: To analyze the efficacy of the different treatments of vesicoureteric
      reflux (VUR) associated with reflex bladder sphincter dyssynergia (RBSD).
      PATIENTS AND METHODS: The medical records of 33 children (28 girls) aged 4 to 12
      years presenting reflex bladder sphincter dyssynergia and vesicoureteric reflux
      have been reviewed. The most common clinical symptom was urinary tract infection.
      Voiding dysfunction included: dysuria, urinary leak, enuresia, urgency,
      constipation. In most cases, vesicoureteric reflux was low grade (grade 1, n=9;
      grade 2, n=18; grade 3, n=6) and bilateral (n=18). Three types of treatments have
      been utilized: reimplantation, reeducation, medical treatment (diet, antibio
      prophylaxis, anti-cholinergics). RESULTS: Eleven children (2 with a solitary
      kidney) underwent early reimplantation which was effective on vesicoureteric
      reflux but 6 of them had post-operative voiding dysfunction and 5 had a new
      episode of urinary infection. Six had reeducation first then they underwent
      reimplantation. Sixteen children had an exclusive medical treatment (13 with
      reeducation). In 9 children vesicoureteric reflux disappeared (one child still
      complains of voiding dysfunction). In 7, voiding dysfunction improved but
      vesicoureteric reflux is still present. CONCLUSION: The management of
      vesicoureteric reflux associated with reflex bladder sphincter dyssynergia is
      complex. Surgery should certainly not be the initial treatment. However, it can
      remain useful if one wishes to get complete resolution of reflux.

PMID- 12511838
TI  - [Bitemporal lobe dysfonction in infantile autism: positron emission tomography
      study].
AB  - PURPOSE: Childhood autism is a severe developmental disorder that impairs the
      acquisition of some of the most important skills in human life. Progress in
      understanding the neural basis of childhood autism requires clear and reliable
      data indicating specific neuroanatomical or neurophysiological abnormalities. The
      purpose of the present study was to research localized brain dysfunction in
      autistic children using functional brain imaging. PATIENTS AND METHODS: Regional
      cerebral blood flow (rCBF) was measured with positron emission tomography (PET)
      in 21 primary autistic children and 10 age-matched non autistic children.
      RESULTS: A statistical parametric analysis of rCBF images revealed significant
      bilateral temporal hypoperfusion in the associative auditory cortex (superior
      temporal gyrus) and in the multimodal cortex (superior temporal sulcus) in the
      autistic group (p<0.001). In addition, temporal hypoperfusion was detected
      individually in 77% of autistic children. CONCLUSION: These findings provide
      robust evidence of well localized functional abnormalities in autistic children
      located in the superior temporal lobe. Such localized abnormalities were not
      detected with the low resolution PET camera,. This study suggests that high
      resolution PET camera combined with statistical parametric mapping is useful to
      understand developmental disorders.

PMID- 12511839
TI  - [Value of factor analysis in a wall motion study: preliminary application in the
      detection of left ventricular segmental contraction ischemic disorders by
      echocardiography].
AB  - PURPOSE: Factor Analysis of Medical Image Sequences (FAMIS) was tested to study
      the regional wall motion of the left ventricle at echocardiography. MATERIALS AND
      METHODS: FAMIS analyzed the time signal curves of each pixel. One flat curve and
      one curve describing the contraction-relaxation of the left ventricle were first
      estimated. The contributions of the curve of each pixel to the two previous
      curves were computed, yielding two "factor images". The spatial distribution of
      positive and negative coefficients of the second factor image was analyzed. The
      evaluation was carried out on 222 segments (20 patients, 18 parasternal short
      axis views, 17 apical four-chamber views, and 15 apical two-chamber views). A
      first echocardiographer reviewed the factor images and the reading was compared
      to the conventional reading of the cine-loops by two other echocardiographers.
      Each segment was scored as normal, hypokinetic, akinetic, or dyskinetic. RESULTS:
      On normal segments, the positive coefficients of the second factor image were on
      the inner side, the negative coefficients were on the outer side. Dyskinesis
      yields the opposite pattern. Hypokinesis and akinesis give intermediate images.
      An absolute concordance was obtained on 71.2% of all segments between the two
      types of reading. Larger discrepancies were found for akinetic and hypokinetic
      segments. CONCLUSION: FAMIS is a promising tool to study regional wall motion of
      the left ventricle.

PMID- 12511840
TI  - [MRI sequences in the detection of cavernous angiomas].
AB  - We prospectively evaluated 30 patients with CNS cavernous angioma with a high
      field (1.5T) magnetic resonance imager. In all patients the MRI protocol
      included: gradient echo T1*-weighted imaging, spin echo T2*-weighted imaging and
      gradient echo T2*-weighted imaging. We evaluated each case for the number of
      lesions detected on each sequence. Gradient echo T2*-weighted imaging with a long
      TE (TE: 35ms) was the most sensitive sequence for the detection of cavernous
      angiomas allowing detection of small lesions that were not identified on the
      other sequences.

PMID- 12511841
TI  - [Persistent sciatic artery: findings using spiral-CT].
AB  - Persistent sciatic artery (PSA), a rare anatomical anomaly, results from lack of
      regression of the embryonic dorsal axial artery combined with a poorly developed
      superficial femoral artery. The authors report the case of a 68-year old man
      presenting with subacute ischemia of the right lower limb. Arteriography showed
      complete bilateral persistent sciatic arteries. CT scan with 3D reconstructions
      was helpful to demonstrate the PSA descending along the back of the thigh and to
      exclude an aneurysmal complication.

PMID- 12511842
TI  - [Superficial siderosis of the central nervous system: a case report].
AB  - Superficial siderosis of the central nervous system is secondary to chronic
      subarachnoid bleeding. However, the underlying etiology is not always detected.
      Superficial siderosis can be diagnosed at MRI by the presence of a hypointense
      rim along the brain surface on gradient echo T2W images. The authors report a
      case of superficial cerebral siderosis where the underlying etiology remained
      undiagnosed in spite of extensive neuroradiological work up.

PMID- 12511843
TI  - [Value of MRI in the diagnosis of unilateral optic nerve aplasia: a case report].
AB  - Optic nerve aplasia is a rare congenital anomaly consisting of complete absence
      of the optic disc and nerve, ganglion cells and nerve fibers, and retinal blood
      vessels. Optic nerve aplasia may be associated or not with anomalies of the eye
      ball, and may be unilateral or more rarely bilateral, the latter sometimes
      associated with major central nervous system anomalies. We report the MRI
      appearance of a case of unilateral optic nerve aplasia associated with
      microphthalmos. Coronal T2 weighted and 3D T1 weighted images disclosed the
      absence of the 3 portions of the optic nerve. This observation shows the
      usefulness of systematic MRI in case of microphthalmos associated with suggestive
      anomalies of the fundus.

PMID- 12511844
TI  - [Polyarthritic manifestations revealing Stickler syndrome].
AB  - Stickler syndrome, also called hereditary arthro-ophthalmopathy is a dominant
      disorder, with poly-epiphyseal dysplasia resulting in early osteoarthritis. It
      usually includes bilateral myopia, that changes little during the follow up
      period, but can lead to retinal detachment. Children with Stickler syndrome can
      show facial dysmorphism that may improve with age, but severe anomalies may exist
      such as Pierre Robin sequence. Our case, a woman, 20-year-old, presents chronic
      polyarthritis which is an unusual feature of this disease. The diagnosis of
      Stickler's syndrome is based on polyepiphyseal dysplasia in skeletal radiography
      and bilateral myopia. Otherwise, this patient has no facial dysmorphism.

PMID- 12511845
TI  - [Quid? Lipoid pneumonia].

PMID- 12511846
TI  - Growth hormone regulated gene expression.
AB  - Growth hormone (GH) regulated gene expression contributes to many of the effects
      of GH on cellular metabolism, growth and differentiation. Study of model systems
      has revealed several mechanisms by which GH regulates gene expression. Regulation
      of expression of the proto-oncogene c-fos involves STAT-, MAPK, and PI-3K
      mediated changes in transcripton factors. STAT 5 plays important roles in
      regulation of spi 2.1 expression and in the sexually dimorphic expression of some
      liver genes. GH-regulated STAT 5 has also been implicated in regulation of other
      physiologically important genes, including those encoding components of the IGF-I
      axis and insulin. Together, these studies provide insight into GH signaling
      mechanisms and diverse physiological roles of GH.

PMID- 12511847
TI  - Structure and regulation of the growth hormone secretagogue receptor.
AB  - Synthetic growth hormone secretagogues (GHS) stimulate growth hormone release
      through binding to a recently cloned specific growth hormone secretagogue
      receptor (GHS-R). Ghrelin, the endogenous ligand of this receptor, is part of a
      new endocrine pathway controlling GH secretion. However, the major physiological
      function of the ghrelin/GHS-R system may be related to the control of energy
      homeostasis. The GHS-R belongs to the family of G-protein coupled receptors. Two
      different receptor variants type 1a and 1b have been described which differ in
      their carboxyl-terminal amino acids. Both types are encoded by a single gene of
      approximately 4.3 kb in length through different processing. The promoter region
      of the human GHS-R was recently characterized. Analysis of the GHS-R may lead to
      new insights into the control of GH secretion and additional physiological roles
      of ghrelin. This review will summarize data regarding the structure of the GHS-R
      gene and the protein encoded, reports investigating the expression and control of
      the GHS-R in various tissues, and studies of the underlying transcriptional
      mechanisms.

PMID- 12511848
TI  - [Ghrelin and GH secretion].
AB  - Ghrelin is an acylated peptide recently isolated from rat and human stomach that
      potently stimulates GH release in vivo and in vitro in rats and humans. Ghrelin
      specifically activates the receptor for the growth hormone secretagogues (GHS)
      and it has been proposed that it may be the endogenous ligand mimicked by these
      synthetic compounds. Ghrelin is primarily produced in endocrine cells of the
      stomach, and to a lesser extent, in other peripheral tissues, including the
      pituitary. Although ghrelin is the most potent GH-secretagogue so far identified,
      its circulating levels do not correlate with those of GH either in physiological
      and pathological conditions. Because of these and many other observations, it may
      be postulated that ghrelin is not physiologically involved in the regulation of
      growth hormone secretion. Nonetheless, ghrelin may serve as a very useful model
      for the development of more potent synthetic GHS, which may be therapeutically
      useful for the treatment of human GH deficiency.

PMID- 12511849
TI  - Growth hormone binding protein. The soluble growth hormone receptor.
AB  - The high affinity growth hormone binding protein (GHBP), the soluble ectodomain
      of the growth hormone receptor (GHR), is an integral part of the growth hormone
      (GH)-insulin-like growth factor axis. Depending on the species, it is either a
      cleavage product of the GHR or a splice variant of the Ghr gene. GHR
      cleavage/GHBP shedding is effected by TACE (TNF-alpha converting enzyme), a
      metalloproteinase of the ADAM family, and possibly related enzymes. The GHBP
      modulates GH action through both inhibitory and enhancing mechanisms. Because of
      its complex in vivo effects, the biological role of the GHBP is still
      incompletely understood. The main clinical application of GHBP measurements is in
      the diagnosis of genetic growth hormone insensitivity (Laron syndrome).

PMID- 12511850
TI  - Growth hormone-releasing hormone and pituitary somatotrope proliferation.
AB  - Growth hormone-releasing hormone (GHRH) is a hypothalamic hormone that is
      essential for normal expansion of the somatotrope lineage during pituitary
      development. Decreased GHRH secretion and/or action leads to impairment of this
      process and somatotrope hypoplasia in both humans and experimental animals.
      Excessive GHRH secretion and/or action result in dysregulated somatotrope
      proliferation, leading to hyperplasia and neoplastic transformation. Our
      understanding of the molecular and morphologic bases for these effects from both
      animal and clinical studies has greatly increased during the past decade.
      However, many features of the cellular pathways remain to be defined, including
      the interaction of other genes in the multistep process of somatotrope
      tumorigenesis.

PMID- 12511851
TI  - Growth hormone receptor antagonists.
AB  - Growth hormone (GH) has profound effects on vertebrate growth and cellular
      differentiation in diverse tissue types. Sexually dimorphic levels of circulating
      GH vary during development and throughout the lifespan. The synthesis and
      secretion of GH by the pituitary gland are precisely controlled. Abnormal levels
      are pathological; hyposecretion in children results in dwarfism while
      hypersecretion results in acromegaly. This review provides an overview of GH and
      the GH/insulin-like growth factor (IGF-1) axis and highlights a GH receptor
      antagonist (i.e. Somavert(R), pegvisomant). This antagonist competes with
      endogenous GH for the receptor and results in suppression of serum insulin-like
      growth factor (IGF-1). Pegvisomant is important for the treatment of acromegaly
      and may have therapeutic implications for certain types of cancer and end organ
      damage due to diabetes.

PMID- 12511852
TI  - A transgenic model to determine the physiological role of liver-derived insulin
      like growth factor I.
AB  - Insulin-like growth factor-I (IGF-I) has important growth promoting and metabolic
      effects and is expressed in virtually every tissue of the body. The highest
      expression is found in the liver but the physiological role of liver-derived IGF
      I is unknown. It has been difficult to separate the endocrine effects of liver
      derived IGF-I from the autocrine/paracrine effects of locally produced IGF-I in
      peripheral tissues. Therefore, we have developed a mouse model with a liver
      specific inducible deletion of the IGF-I gene. The liver-IGF-I deficient mouse
      have dramatically reduced (>80%) serum IGF-I levels, demonstrating that the major
      part of serum IGF-I is liver-derived. Surprisingly, liver-IGF-I deficient mice
      demonstrate a normal appendicular skeletal growth up to at least 12 months of age
      despite the dramatic decrease in circulating IGF-I levels, indicating that liver
      derived IGF-I is not required for appendicular skeletal growth. However, the
      adult axial skeletal growth is clearly reduced in the liver-IGF-I deficient mice.
      Furthermore, the amount of cortical bone is reduced due to decreased radial
      growth of the cortical bone while the amount of trabecular bone is unchanged in
      the liver-IGF-I deficient mice. The decreased levels of circulating IGF-I are
      associated with increased serum levels of growth hormone (GH), indicating a role
      for liver-derived IGF-I in the negative feedback regulation of GH secretion.
      Measurements of factors regulating GH-secretion in the pituitary and in the
      hypothalamus revealed an increased expression of growth hormone releasing hormone
      (GHRH) and growth hormone secretagogue (GHS) receptors in the pituitary of liver
      IGF-I deficient mice. This in turn results in an increased sensitivity to
      systemically administered GHRH and GHS, demonstrating that the regulatory action
      of liver-derived IGF-I on GH secretion is at the pituitary rather than at the
      hypothalamic level. The liver is an important metabolic organ and liver-IGF-I
      deficient mice are markedly hyperinsulinemic and yet normoglycemic, consistent
      with an adequately compensated insulin resistance. Interestingly, liver-IGF-I
      deficient mice display a reduced age-dependent fat mass accumulation compared
      with control mice. In conclusion, liver-derived IGF-I is important for
      carbohydrate- and lipid-metabolism and for the regulation of GH-secretion at the
      pituitary level. Furthermore, it regulates adult axial skeletal growth and
      cortical radial growth while it is not required for appendicular skeletal growth.

PMID- 12511854
TI  - Issues in the management of bacterial sinusitis.
AB  - Office visits for acute bacterial rhinosinusitis (ABRS) have increased steadily
      in the past 2 decades, and ABRS accounted for 0.4% of ambulatory diagnoses in
      1995, ranking as the fifth most common diagnosis for which an antibiotic is
      prescribed. ABRS typically begins as a viral respiratory tract infection, but
      bacterial growth is demonstrated in 60% of adults with upper respiratory tract
      infection symptoms of at least 10 days duration. Important factors to consider
      when selecting an antibiotic regimen for ABRS include: severity of disease, rate
      of disease progression, earlier antibiotic treatment, regional resistance rates,
      and, in children, an age <5 years and attendance in day care centers. The most
      prevalent causative pathogens of sinusitis are Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis. Antimicrobial agent use is
      under significant scrutiny in this era of emerging bacterial resistance, and
      antibiotic treatment for sinusitis should include consideration of drug
      pharmacodynamics. Several agents, once considered first-line therapies, can no
      longer be considered dependable in this role. Rather, newer antibiotics may be
      called on to provide efficacy and forestall additional antimicrobial resistance
      among respiratory tract pathogens.

PMID- 12511855
TI  - Pharmacodynamic considerations for the selection of oral cephalosporins in the
      treatment of rhinosinusitis.
AB  - The elimination of an infection occurs when the antibiotic reaches the site of
      the pathogen in adequate concentrations for an appropriate length of time. To
      predict whether an antibiotic will achieve this goal, one must have a familiarity
      with pharmacodynamic concepts that integrate the drug's microbiological activity,
      its pharmacokinetic properties, and its mode of bacterial killing. For the
      cephalosporins, it is the time or duration that the concentrations in serum or
      interstitial fluid remain above their mean inhibitory concentration for the
      pathogen that best correlates with clinical outcomes. The application of this
      pharmacodynamic profile can assist in the decision process to distinguish one
      oral cephalosporin from another and, therefore, provides an opportunity for
      maximizing the probability of good clinical outcomes while minimizing the
      potential for the selection of resistance.

PMID- 12511856
TI  - Activity of oral beta-lactam antimicrobial agents versus respiratory tract
      isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
      catarrhalis in the era of antibiotic resistance.
AB  - The management of outpatient respiratory tract infections with oral beta-lactam
      antimicrobial agents has been complicated by the emergence of beta-lactamase
      producing strains of Haemophilus influenzae and Moraxella catarrhalis and
      isolates of Streptococcus pneumoniae that express varying levels of beta-lactam
      resistance because of altered penicillin-binding proteins. There is no question
      that all 3 of these important respiratory tract pathogens have changed
      conspicuously in the context of decreased activity of beta-lactam antimicrobial
      agents. The question arises, what does this change mean from a clinical
      perspective? In this review, the in vitro activity of various oral beta-lactam
      antimicrobial agents versus contemporary isolates of H influenzae, M catarrhalis,
      and S pneumoniae will be compared. The approach that is used in defining
      organisms as being susceptible or resistant to beta-lactam antimicrobial agents
      will be elucidated. Finally, an effort will be made to assess the ramifications
      of beta-lactam resistance for therapeutic efficacy in patients with respiratory
      tract infections caused by these 3 bacteria. We conclude that, notwithstanding
      diminished beta-lactam activity for many clinical isolates of H influenzae, M
      catarrhalis, and S pneumoniae, certain agents remain effective in treating
      outpatient respiratory tract infections.

PMID- 12511857
TI  - Management update of acute bacterial rhinosinusitis and the use of cefdinir.
AB  - The pathogenesis, bacteriology, diagnosis, and antimicrobial treatment of acute
      bacterial rhinosinusitis (ABRS) is reviewed. Most cases of ABRS arise as
      complications of the rhinosinusitis of colds and other acute viral respiratory
      infections. Nose blowing during colds may be a risk factor for ABRS by propelling
      bacteria-laden nasal fluid into the sinus cavity. The bacterial causes of ABRS
      continue to be S pneumoniae. H influenzae, other streptococcal species, M
      catarrhalis, anaerobes, and S aureus. Clinical diagnosis of ABRS is based on
      obtaining a history of a cold or influenza-like illness that is no better or
      worse after >/=7 days. A 10-day course of treatment with an antimicrobial
      effective against resistant S pneumoniae and H influenzae is recommended. A
      clinical trial was reviewed in which cefdinir was effective in treating ABRS.

PMID- 12511858
TI  - Plasma membrane monoamine transporters: structure, regulation and function.

PMID- 12511859
TI  - Non-spatially lateralized mechanisms in hemispatial neglect.

PMID- 12511860
TI  - Mapping brain asymmetry.

PMID- 12511861
TI  - Unfolding the role of protein misfolding in neurodegenerative diseases.

PMID- 12511862
TI  - Neuroprotective gene therapy against acute neurological insults.

PMID- 12511863
TI  - Viewing the brain through the master hand of Ramon y Cajal.

PMID- 12511864
TI  - The contribution of Santiago Ramon y Cajal to functional neuroscience.

PMID- 12511865
TI  - Border-cell migration: the race is on.
AB  - The conversion of stationary epithelial cells into migratory, invasive cells is
      important for normal embryonic development and tumour metastasis. Border-cell
      migration in the ovary of Drosophila melanogaster has emerged as a simple,
      genetically tractable model for studying this process. Three distinct signals,
      which are also upregulated in cancer, control border-cell migration, so
      identifying further genes that are involved in border-cell migration could
      provide new insights into tumour invasion.

PMID- 12511866
TI  - Replicating by the clock.
AB  - The eukaryotic genome is divided into well-defined DNA regions that are
      programmed to replicate at different times during S phase. Active genes are
      generally associated with early replication, whereas inactive genes replicate
      late. This expression pattern might be facilitated by the differential
      restructuring of chromatin at the time of replication in early or late S phase.

PMID- 12511867
TI  - CD44: from adhesion molecules to signalling regulators.
AB  - Cell-adhesion molecules, once believed to function primarily in tethering cells
      to extracellular ligands, are now recognized as having broader functions in
      cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new
      aspects to these roles by participating in signal-transduction processes--not
      only by establishing specific transmembrane complexes, but also by organizing
      signalling cascades through association with the actin cytoskeleton. CD44 and its
      associated partner proteins monitor changes in the extracellular matrix that
      influence cell growth, survival and differentiation.

PMID- 12511868
TI  - Nongenomic actions of steroid hormones.
AB  - Steroid hormones modulate many physiological processes. The effects of steroids
      that are mediated by the modulation of gene expression are known to occur with a
      time lag of hours or even days. Research that has been carried out mainly in the
      past decade has identified other responses to steroids that are much more rapid
      and take place in seconds or minutes. These responses follow nongenomic pathways,
      and they are not rare.

PMID- 12511869
TI  - Entry of viruses through the epithelial barrier: pathogenic trickery.
AB  - Mucosal surfaces--such as the lining of the gut or the reproductive tract--are
      the main point of entry for viruses into the body. As such, almost all viruses
      interact with epithelial cells, and make use of the normal epithelial signalling
      and trafficking pathways of the host cell. In addition to protein receptors,
      carbohydrate chains of proteoglycans and epithelial-membrane glycosphingolipids
      have emerged as a new class of receptors for viral attachment to the host cell.

PMID- 12511870
TI  - The sarcoplasmic reticulum: its discovery and rediscovery.
AB  - In 1902, Emilio Veratti made the most accurate description, by light microscopy,
      of a reticular structure in the sarcoplasm. However, this structure was almost
      lost to man's knowledge for more than 50 years and was rediscovered during the
      1960s, following the introduction of electron microscopy. Since then,
      biochemistry, electron microscopy and electrophysiology have unravelled the
      crucial role of the sarcoplasmic reticulum in the control of muscle contraction.

PMID- 12511871
TI  - Is proteomics heading in the wrong direction?
AB  - Proteomics is now considered to be one of the most important 'post-genome'
      approaches to help us understand gene function. In fact, several genomics
      companies have launched large-scale proteomics projects, and have started to
      annotate the entire human proteome. The 'holistic view' painted by a human
      proteome project is seductive, but is it realistic?

PMID- 12511872
TI  - Intracellular pathways of CD1 antigen presentation.
AB  - Each of the human CD1 proteins takes a different route through secretory and
      endocytic compartments before finally arriving at the cell surface, where these
      proteins present glycolipid antigens to T cells. Recent studies have shown that
      adaptor-protein complexes and CD1-associated chaperones control not only CD1
      trafficking, but also the development and activation of CD1-restricted T cells.
      This indicates that CD1 proteins, similar to MHC class I and II molecules,
      selectively acquire certain antigens in distinct cellular subcompartments. Here,
      we summarize evidence supporting the hypothesis that CD1 proteins use separate,
      but parallel, pathways to survey endosomal compartments differentially for lipid
      antigens.

PMID- 12511873
TI  - Alternative activation of macrophages.
AB  - The classical pathway of interferon-gamma-dependent activation of macrophages by
      T helper 1 (T(H)1)-type responses is a well-established feature of cellular
      immunity to infection with intracellular pathogens, such as Mycobacterium
      tuberculosis and HIV. The concept of an alternative pathway of macrophage
      activation by the T(H)2-type cytokines interleukin-4 (IL-4) and IL-13 has gained
      credence in the past decade, to account for a distinctive macrophage phenotype
      that is consistent with a different role in humoral immunity and repair. In this
      review, I assess the evidence in favour of alternative macrophage activation in
      the light of macrophage heterogeneity, and define its limits and relevance to a
      range of immune and inflammatory conditions.

PMID- 12511874
TI  - Viral mimicry of cytokines, chemokines and their receptors.
AB  - Viruses have evolved elegant mechanisms to evade detection and destruction by the
      host immune system. One of the evasion strategies that have been adopted by large
      DNA viruses is to encode homologues of cytokines, chemokines and their receptors-
      molecules that have a crucial role in control of the immune response. Viruses
      have captured host genes or evolved genes to target specific immune pathways, and
      so viral genomes can be regarded as repositories of important information about
      immune processes, offering us a viral view of the host immune system. The study
      of viral immunomodulatory proteins might help us to uncover new human genes that
      control immunity, and their characterization will increase our understanding of
      not only viral pathogenesis, but also normal immune mechanisms. Moreover, viral
      proteins indicate strategies of immune modulation that might have therapeutic
      potential.

PMID- 12511875
TI  - Hepatic T cells and liver tolerance.
AB  - The T-cell biology of the liver is unlike that of any other organ. The local
      lymphocyte population is enriched in natural killer (NK) and NKT cells, which
      might have crucial roles in the recruitment of circulating T cells. A large
      macrophage population and the efficient trafficking of dendritic cells from
      sinusoidal blood to lymph promote antigen trapping and T-cell priming, but the
      local presentation of antigen causes T-cell inactivation, tolerance and
      apoptosis. These local mechanisms might result from the need to maintain
      immunological silence to harmless antigenic material in food. The overall bias of
      intrahepatic T-cell responses towards tolerance might account for the survival of
      liver allografts and for the persistence of some liver pathogens.

PMID- 12511876
TI  - Intestinal IgA synthesis: regulation of front-line body defences.
AB  - Immunoglobulin A is the most abundant immunoglobulin isotype in mucosal
      secretions. In this review, we summarize recent advances in our understanding of
      the sites, mechanisms and functions of intestinal IgA synthesis in mice. On the
      basis of these recent findings, we propose an updated model for the induction and
      regulation of IgA responses in the gut. In addition, we discuss new insights into
      the role of IgA in the maintenance of gut homeostasis and into the reciprocal
      interactions between gut B cells and the bacterial flora.

PMID- 12511877
TI  - The autoantibody repertoire: searching for order.
AB  - The spontaneously occurring autoantibodies that are associated with human
      diseases bear the hallmarks of a typical immune response. The repertoire of
      autoantibodies is surprisingly limited, however, and is the same in both humans
      and mice. Neither molecular mimicry nor immune dysregulation accounts for this
      unexpectedly narrow focus of specificities. Experimental data on the properties
      of the target autoantigens--such as their structure, catabolism, exposure to the
      immune system after cell death and recently described immunostimulatory effects
      on immature dendritic cells--indicate that these properties, in conjunction with
      the tissue microenvironment, help to select the autoantibody repertoire.

PMID- 12511878
TI  - A road less travelled: large animal models in immunological research.
AB  - The main advances in immunology have been forged or underpinned by animal
      experiments. However, animal research now focuses excessively on one laboratory
      species, and there is too much redundant repetition and too few transfers from
      basic discovery to successful clinical application. These features can be
      improved markedly by placing more emphasis on biological relevance when
      evaluating animal models and by taking greater advantage of the unique
      experimental opportunities that are offered by large animals.

PMID- 12511880
TI  - Cell biology in the Antarctic: studying life in the freezer.
AB  - Many classical biologists working in Antarctica have 'gone molecular' to study
      the physiological basis for life on or below the ice. Investigating the
      remarkable adaptations of specific cells, organelles and molecules to this
      extreme environment can provide new perspectives on the processes studied in
      conventional experimental organisms.

PMID- 12511881
TI  - New insights into an enigmatic tumour suppressor.

PMID- 12511882
TI  - Defying death: showing Bcl-2 the way home.

PMID- 12511884
TI  - A genetic hierarchy controlling cell polarity.

PMID- 12511887
TI  - Eukaryotic cells and microbial pathogens: a familiar couple take centre stage.
AB  - The interaction of a microbial pathogen with its host is a highly dynamic process
      shaped by evolution. Understanding cellular responses to microbial products is
      essential for a complete understanding of virulence. Similarly, studies aimed at
      determining how a particular virulence factor functions have helped unravel
      molecular mechanisms that govern eukaryotic cellular events. These two seemingly
      diverse areas were brought together on the beautiful Spanish Costa Brava in a
      recent meeting (October 13-17, 2002) sponsored by European Research Conferences
      (EURESCO) and the European Molecular Biology Organization (EMBO).

PMID- 12511891
TI  - It's a gas.

PMID- 12511892
TI  - Happier, hornier, hairier.

PMID- 12511893
TI  - Puzzling industry response to ProdiGene fiasco.

PMID- 12511894
TI  - Antisoma-Roche deal--a new kind of buyout?

PMID- 12511895
TI  - Hyseq-Variagenics merger signals end of the line.

PMID- 12511896
TI  - New products highlight ambiguity of orphan drug law.

PMID- 12511897
TI  - Europe angers US with strict GM labeling.

PMID- 12511899
TI  - The sigmoidal curve of cancer.

PMID- 12511900
TI  - Cytokines--strategic weapons in germ warfare?

PMID- 12511903
TI  - Decoding the literature on genetic variation.

PMID- 12511904
TI  - The master mammal.

PMID- 12511905
TI  - Quantum dots finally come of age.

PMID- 12511906
TI  - Human therapeutic proteins from silkworms.

PMID- 12511907
TI  - Antibody jabs for plant enzymes.

PMID- 12511908
TI  - Harnessing immunity for cancer marker discovery.

PMID- 12511910
TI  - Enzo Biochem v. Gen-Probe: complying with the written description requirement
      under US patent law.

PMID- 12511911
TI  - Recent patents in nucleic acid synthesis and sequencing.

PMID- 12511915
TI  - Managing your compensation expectations in today's environment.

PMID- 12511916
TI  - Nature in 2003.

PMID- 12511917
TI  - Overseas abuse of China's development.

PMID- 12511918
TI  - Petition calls for clampdown on absentee Chinese researchers.

PMID- 12511919
TI  - Human cloning claim sparks fear of Senate backlash.

PMID- 12511920
TI  - Law sends laboratories into pathogen panic.

PMID- 12511921
TI  - Biotech critic tries to sew up research on chimaeras.

PMID- 12511922
TI  - Bleak outlook for universities as state budget deficits bite.

PMID- 12511923
TI  - Joint European plan will tackle Africa's killer diseases.

PMID- 12511926
TI  - A window on the inner Earth.

PMID- 12511925
TI  - The law of the jungle.

PMID- 12511927
TI  - Academics are teachers and colleagues too.

PMID- 12511928
TI  - Malaria--there could be a third way.

PMID- 12511929
TI  - Scientific research and the human condition.

PMID- 12511930
TI  - 1903 and all that.

PMID- 12511935
TI  - Protein knots: A tangled problem.

PMID- 12511936
TI  - Animal behaviour: The lobster navigators.

PMID- 12511937
TI  - Quantum computing: Putting it into practice.

PMID- 12511938
TI  - Neurobiology: The importance of depression.

PMID- 12511939
TI  - Planetary science: Sodium at Io.

PMID- 12511941
TI  - Condensed-matter physics: Two bodies are better than one.

PMID- 12511940
TI  - Molecular evolution: Duplication, duplication.

PMID- 12511943
TI  - Obituary: Arthur T. Winfree (1942-2002).

PMID- 12511944
TI  - Biomechanics: A catapult action for rapid limb protraction.

PMID- 12511945
TI  - Outer planets: Origins of atmospheric zonal winds.

PMID- 12511946
TI  - A globally coherent fingerprint of climate change impacts across natural systems.
AB  - Causal attribution of recent biological trends to climate change is complicated
      because non-climatic influences dominate local, short-term biological changes.
      Any underlying signal from climate change is likely to be revealed by analyses
      that seek systematic trends across diverse species and geographic regions;
      however, debates within the Intergovernmental Panel on Climate Change (IPCC)
      reveal several definitions of a 'systematic trend'. Here, we explore these
      differences, apply diverse analyses to more than 1,700 species, and show that
      recent biological trends match climate change predictions. Global meta-analyses
      documented significant range shifts averaging 6.1 km per decade towards the poles
      (or metres per decade upward), and significant mean advancement of spring events
      by 2.3 days per decade. We define a diagnostic fingerprint of temporal and
      spatial 'sign-switching' responses uniquely predicted by twentieth century
      climate trends. Among appropriate long-term/large-scale/multi-species data sets,
      this diagnostic fingerprint was found for 279 species. This suite of analyses
      generates 'very high confidence' (as laid down by the IPCC) that climate change
      is already affecting living systems.

PMID- 12511947
TI  - Wave-like properties of solar supergranulation.
AB  - Supergranulation on the surface of the Sun is a pattern of horizontal outflows,
      outlined by a network of small magnetic features, with a distinct scale of 30
      million metres and an apparent lifetime of one day. It is generally believed that
      supergranulation corresponds to a preferred 'cellular' scale of thermal
      convection; rising magnetic fields are dragged by the outflows and concentrated
      into 'ropes' at the 'cell' boundaries. But as the convection zone is highly
      turbulent and stratified, numerical modelling has proved to be difficult and the
      dynamics remain poorly understood. Moreover, there is as yet no explanation for
      the observation that the pattern appears to rotate faster around the Sun than the
      magnetic features. Here we report observations showing that supergranulation
      undergoes oscillations and supports waves with periods of 6-9 days. The waves are
      predominantly prograde, which explains the apparent super-rotation of the
      pattern. The rotation of the plasma through which the pattern propagates is
      consistent with the motion of the magnetic network.

PMID- 12511948
TI  - Volcanically emitted sodium chloride as a source for Io's neutral clouds and
      plasma torus.
AB  - The atmosphere of Jupiter's satellite Io is extremely tenuous, time variable and
      spatially heterogeneous. Only a few molecules--SO2, SO and S2--have previously
      been identified as constituents of this atmosphere, and possible sources include
      frost sublimation, surface sputtering and active volcanism. Io has been known for
      almost 30 years to be surrounded by a cloud of Na, which requires an as yet
      unidentified atmospheric source of sodium. Sodium chloride has been recently
      proposed as an important atmospheric constituent, based on the detection of
      chlorine in Io's plasma torus and models of Io's volcanic gases. Here we report
      the detection of NaCl in Io's atmosphere; it constitutes only approximately 0.3%
      when averaged over the entire disk, but is probably restricted to smaller regions
      than SO2 because of its rapid photolysis and surface condensation. Although the
      inferred abundance of NaCl in volcanic gases is lower than predicted, those
      volcanic emissions provide an important source of Na and Cl in Io's neutral
      clouds and plasma torus.

PMID- 12511949
TI  - Implementation of the Deutsch-Jozsa algorithm on an ion-trap quantum computer.
AB  - Determining classically whether a coin is fair (head on one side, tail on the
      other) or fake (heads or tails on both sides) requires an examination of each
      side. However, the analogous quantum procedure (the Deutsch-Jozsa algorithm)
      requires just one examination step. The Deutsch-Jozsa algorithm has been realized
      experimentally using bulk nuclear magnetic resonance techniques, employing
      nuclear spins as quantum bits (qubits). In contrast, the ion trap processor
      utilises motional and electronic quantum states of individual atoms as qubits,
      and in principle is easier to scale to many qubits. Experimental advances in the
      latter area include the realization of a two-qubit quantum gate, the entanglement
      of four ions, quantum state engineering and entanglement-enhanced phase
      estimation. Here we exploit techniques developed for nuclear magnetic resonance
      to implement the Deutsch-Jozsa algorithm on an ion-trap quantum processor, using
      as qubits the electronic and motional states of a single calcium ion. Our ion
      based implementation of a full quantum algorithm serves to demonstrate
      experimental procedures with the quality and precision required for complex
      computations, confirming the potential of trapped ions for quantum computation.

PMID- 12511950
TI  - Quasi-phase-matched generation of coherent extreme-ultraviolet light.
AB  - High-harmonic generation is a well-known method of producing coherent extreme
      ultraviolet (EUV) light, with photon energies up to about 0.5 keV (refs 1, 2).
      This is achieved by focusing a femtosecond laser into a gas, and high harmonics
      of the fundamental laser frequency are radiated in the forward direction.
      However, although this process can generate high-energy photons, efficient high
      harmonic generation has been demonstrated only for photon energies of the order
      50-100 eV (ref. 5). Ionization of the gas prevents the laser and the EUV light
      from propagating at the same speed, which severely limits the conversion
      efficiency. Here we report a technique to overcome this problem, and demonstrate
      quasi-phase-matched frequency conversion of laser light into EUV. Using a
      modulated hollow-core waveguide to periodically vary the intensity of the laser
      light driving the conversion, we efficiently generate EUV light even in the
      presence of substantial ionization. The use of a modulated fibre shifts the
      energy spectrum of the high-harmonic light to significantly higher photon
      energies than would otherwise be possible. We expect that this technique could
      form the basis of coherent EUV sources for advanced lithography and high
      resolution imaging applications. In future work, it might also be possible to
      generate isolated attosecond pulses.

PMID- 12511951
TI  - Electroluminescent device with reversible switching between red and green
      emission.
AB  - Research on new materials for organic electroluminescence has recently focused
      strongly on phosphorescent emitters, with the aim of increasing the emission
      efficiency and stability. Here we report the fabrication of a simple
      electroluminescent device, based on a semiconducting polymer combined with a
      phosphorescent complex, that shows fully reversible voltage-dependent switching
      between green and red light emission. The active material is made of a
      polyphenylenevinylene (PPV) derivative molecularly doped with a homogeneously
      dispersed dinuclear ruthenium complex, which fulfils the dual roles of triplet
      emitter and electron transfer mediator. At forward bias (+4 V), the excited state
      of the ruthenium compound is populated, and the characteristic red emission of
      the complex is observed. On reversing the bias (-4 V), the lowest excited singlet
      state of the polymer host is populated, with subsequent emission of green light.
      The mechanism for the formation of the excited state of the PPV derivative
      involves the ruthenium dinuclear complex in a stepwise electron transfer process
      that finally leads to efficient charge recombination reaction on the polymer.

PMID- 12511952
TI  - Fingerprints of global warming on wild animals and plants.
AB  - Over the past 100 years, the global average temperature has increased by
      approximately 0.6 degrees C and is projected to continue to rise at a rapid rate.
      Although species have responded to climatic changes throughout their evolutionary
      history, a primary concern for wild species and their ecosystems is this rapid
      rate of change. We gathered information on species and global warming from 143
      studies for our meta-analyses. These analyses reveal a consistent temperature
      related shift, or 'fingerprint', in species ranging from molluscs to mammals and
      from grasses to trees. Indeed, more than 80% of the species that show changes are
      shifting in the direction expected on the basis of known physiological
      constraints of species. Consequently, the balance of evidence from these studies
      strongly suggests that a significant impact of global warming is already
      discernible in animal and plant populations. The synergism of rapid temperature
      rise and other stresses, in particular habitat destruction, could easily disrupt
      the connectedness among species and lead to a reformulation of species
      communities, reflecting differential changes in species, and to numerous
      extirpations and possibly extinctions.

PMID- 12511953
TI  - True navigation and magnetic maps in spiny lobsters.
AB  - Animals are capable of true navigation if, after displacement to a location where
      they have never been, they can determine their position relative to a goal
      without relying on familiar surroundings, cues that emanate from the destination,
      or information collected during the outward journey. So far, only a few animals,
      all vertebrates, have been shown to possess true navigation. Those few
      invertebrates that have been carefully studied return to target areas using path
      integration, landmark recognition, compass orientation and other mechanisms that
      cannot compensate for displacements into unfamiliar territory. Here we report,
      however, that the spiny lobster Panulirus argus oriented reliably towards a
      capture site when displaced 12-37 km to unfamiliar locations, even when deprived
      of all known orientation cues en route. Little is known about how lobsters and
      other animals determine position during true navigation. To test the hypothesis
      that lobsters derive positional information from the Earth's magnetic field,
      lobsters were exposed to fields replicating those that exist at specific
      locations in their environment. Lobsters tested in a field north of the capture
      site oriented themselves southwards, whereas those tested in a field south of the
      capture site oriented themselves northwards. These results imply that true
      navigation in spiny lobsters, and perhaps in other animals, is based on a
      magnetic map sense.

PMID- 12511954
TI  - Role of duplicate genes in genetic robustness against null mutations.
AB  - Deleting a gene in an organism often has little phenotypic effect, owing to two
      mechanisms of compensation. The first is the existence of duplicate genes: that
      is, the loss of function in one copy can be compensated by the other copy or
      copies. The second mechanism of compensation stems from alternative metabolic
      pathways, regulatory networks, and so on. The relative importance of the two
      mechanisms has not been investigated except for a limited study, which suggested
      that the role of duplicate genes in compensation is negligible. The availability
      of fitness data for a nearly complete set of single-gene-deletion mutants of the
      Saccharomyces cerevisiae genome has enabled us to carry out a genome-wide
      evaluation of the role of duplicate genes in genetic robustness against null
      mutations. Here we show that there is a significantly higher probability of
      functional compensation for a duplicate gene than for a singleton, a high
      correlation between the frequency of compensation and the sequence similarity of
      two duplicates, and a higher probability of a severe fitness effect when the
      duplicate copy that is more highly expressed is deleted. We estimate that in S.
      cerevisiae at least a quarter of those gene deletions that have no phenotype are
      compensated by duplicate genes.

PMID- 12511955
TI  - Synaptic depression in the localization of sound.
AB  - Short-term synaptic plasticity, which is common in the central nervous system,
      may contribute to the signal processing functions of both temporal integration
      and coincidence detection. For temporal integrators, whose output firng rate
      depends on a running average of recent synaptic inputs, plasticity modulates
      input synaptic strength and thus may directly control signalling gain and the
      function of neural networks. But the firing probability of an ideal coincidence
      detector would depend on the temporal coincidence of events rather than on the
      average frequency of synaptic events. Here we have examined a specific case of
      how synaptic plasticity can affect temporal coincidence detection, by
      experimentally characterizing synaptic depression at the synapse between neurons
      in the nucleus magnocellularis and coincidence detection neurons in the nucleus
      laminaris in the chick auditory brainstem. We combine an empirical description of
      this depression with a biophysical model of signalling in the nucleus laminaris.
      The resulting model predicts that synaptic depression provides an adaptive
      mechanism for preserving interaural time-delay information (a proxy for the
      location of sound in space) despite the confounding effects of sound-intensity
      related information. This mechanism may help nucleus laminaris neurons to pass
      specific sound localization information to higher processing centres.

PMID- 12511956
TI  - Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking
      behaviour.
AB  - Cocaine addiction is thought to involve persistent neurobiological changes that
      facilitate relapse to drug use despite efforts to abstain. But the propensity for
      relapse may be reduced by extinction training--a form of inhibitory learning that
      progressively reduces cocaine-seeking behaviour in the absence of cocaine reward.
      Here we show that extinction training during withdrawal from chronic cocaine self
      administration induces experience-dependent increases in the GluR1 and GluR2/3
      subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)
      glutamate receptors in the nucleus accumbens shell, a brain region that is
      critically involved in cocaine reward. Increases in the GluR1 subunit are
      positively associated with the level of extinction achieved during training,
      suggesting that GluR1 may promote extinction of cocaine seeking. Indeed, viral
      mediated overexpression of both GluR1 and GluR2 in nucleus accumbens shell
      neurons facilitates extinction of cocaine- but not sucrose-seeking responses. A
      single extinction training session, when conducted during GluR subunit
      overexpression, attenuates stress-induced relapse to cocaine seeking even after
      GluR overexpression declines. Our findings indicate that extinction-induced
      plasticity in AMPA receptors may facilitate control over cocaine seeking by
      restoring glutamatergic tone in the nucleus accumbens, and may reduce the
      propensity for relapse under stressful situations in prolonged abstinence.

PMID- 12511957
TI  - Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic
      HDL endocytosis.
AB  - The effect of high-density lipoprotein (HDL) in protecting against
      atherosclerosis is usually attributed to its role in 'reverse cholesterol
      transport'. In this process, HDL particles mediate the efflux and the transport
      of cholesterol from peripheral cells to the liver for further metabolism and bile
      excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners
      in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for
      apolipoprotein A-I (apoA-I) was previously identified on the surface of
      hepatocytes. Here we show that this receptor is identical to the beta-chain of
      ATP synthase, a principal protein complex of the mitochondrial inner membrane.
      Different experimental approaches confirm this ectopic localization of components
      of the ATP synthase complex and the presence of ATP hydrolase activity at the
      hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis
      of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly
      on the generation of ADP. We confirm this effect on endocytosis in perfused rat
      liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound
      ATP synthase has a previously unsuspected role in modulating the concentrations
      of extracellular ADP and is regulated by a principal plasma apolipoprotein.

PMID- 12511958
TI  - Chloroplast to nucleus communication triggered by accumulation of Mg
      protoporphyrinIX.
AB  - Plant cells coordinately regulate the expression of nuclear and plastid genes
      that encode components of the photosynthetic apparatus. Nuclear genes that
      regulate chloroplast development and chloroplast gene expression provide part of
      this coordinate control. There is evidence that information also flows in the
      opposite direction, from chloroplasts to the nucleus. Until now, at least three
      different signalling pathways have been identified that originate in the plastid
      and control nuclear gene expression but the molecular nature of these signals has
      remained unknown. Here we show that the tetrapyrrole intermediate Mg
      protoporphyrin (Mg-ProtoIX) acts as a signalling molecule in one of the
      signalling pathways between the chloroplast and nucleus. Accumulation of Mg
      ProtoIX is both necessary and sufficient to regulate the expression of many
      nuclear genes encoding chloroplastic proteins associated with photosynthesis.

PMID- 12511959
TI  - Moesin functions antagonistically to the Rho pathway to maintain epithelial
      integrity.
AB  - Two prominent characteristics of epithelial cells, apical-basal polarity and a
      highly ordered cytoskeleton, depend on the existence of precisely localized
      protein complexes associated with the apical plasma membrane, and on a separate
      machinery that regulates the spatial order of actin assembly. ERM (ezrin,
      radixin, moesin) proteins have been proposed to link transmembrane proteins to
      the actin cytoskeleton in the apical domain, suggesting a structural role in
      epithelial cells, and they have been implicated in signalling pathways. Here, we
      show that the sole Drosophila ERM protein Moesin functions to promote cortical
      actin assembly and apical-basal polarity. As a result, cells lacking Moesin lose
      epithelial characteristics and adopt invasive migratory behaviour. Our data
      demonstrate that Moesin facilitates epithelial morphology not by providing an
      essential structural function, but rather by antagonizing activity of the small
      GTPase Rho. Thus, Moesin functions in maintaining epithelial integrity by
      regulating cell-signalling events that affect actin organization and polarity.
      Furthermore, our results show that there is negative feedback between ERM
      activation and activity of the Rho pathway.

PMID- 12511960
TI  - A cryo-electron microscopic study of ribosome-bound termination factor RF2.
AB  - Protein synthesis takes place on the ribosome, where genetic information carried
      by messenger RNA is translated into a sequence of amino acids. This process is
      terminated when a stop codon moves into the ribosomal decoding centre (DC) and is
      recognized by a class-1 release factor (RF). RFs have a conserved GGQ amino-acid
      motif, which is crucial for peptide release and is believed to interact directly
      with the peptidyl-transferase centre (PTC) of the 50S ribosomal subunit. Another
      conserved motif of RFs (SPF in RF2) has been proposed to interact directly with
      stop codons in the DC of the 30S subunit. The distance between the DC and PTC is
      approximately 73 A. However, in the X-ray structure of RF2, SPF and GGQ are only
      23 A apart, indicating that they cannot be at DC and PTC simultaneously. Here we
      show that RF2 is in an open conformation when bound to the ribosome, allowing GGQ
      to reach the PTC while still allowing SPF-stop-codon interaction. The results
      indicate new interpretations of accuracy in termination, and have implications
      for how the presence of a stop codon in the DC is signalled to PTC.

PMID- 12511961
TI  - Structure of the Escherichia coli ribosomal termination complex with release
      factor 2.
AB  - Termination of protein synthesis occurs when the messenger RNA presents a stop
      codon in the ribosomal aminoacyl (A) site. Class I release factor proteins (RF1
      or RF2) are believed to recognize stop codons via tripeptide motifs, leading to
      release of the completed polypeptide chain from its covalent attachment to
      transfer RNA in the ribosomal peptidyl (P) site. Class I RFs possess a conserved
      GGQ amino-acid motif that is thought to be involved directly in protein-transfer
      RNA bond hydrolysis. Crystal structures of bacterial and eukaryotic class I RFs
      have been determined, but the mechanism of stop codon recognition and peptidyl
      tRNA hydrolysis remains unclear. Here we present the structure of the Escherichia
      coli ribosome in a post-termination complex with RF2, obtained by single-particle
      cryo-electron microscopy (cryo-EM). Fitting the known 70S and RF2 structures into
      the electron density map reveals that RF2 adopts a different conformation on the
      ribosome when compared with the crystal structure of the isolated protein. The
      amino-terminal helical domain of RF2 contacts the factor-binding site of the
      ribosome, the 'SPF' loop of the protein is situated close to the mRNA, and the
      GGQ-containing domain of RF2 interacts with the peptidyl-transferase centre
      (PTC). By connecting the ribosomal decoding centre with the PTC, RF2 functionally
      mimics a tRNA molecule in the A site. Translational termination in eukaryotes is
      likely to be based on a similar mechanism.

PMID- 12511964
TI  - Out in the cold.

PMID- 12511965
TI  - Electric interactions at the lipid membrane surface.
AB  - This work presents the results of an experimental study and of computer
      simulations concerning electric interactions in the surface layer of egg yolk
      lecithin (EYL) liposome membranes. The surface layer is formed by EYL polar
      heads, which possess features of electric dipoles, and positive charged polar
      heads belonging to admixtures of quaternary ammonium salts (AS). The results of
      the experimental study are in good agreement with the ones of the computer
      simulations. It was found that fluidity of the membranes, at a given
      concentration of AS, obtains the extremal (minimal) value. Similarly, the binding
      energy of the dipoles-positive charges system behaves like that in computer
      simulations. Moreover, the locations of the fluidity extremum and those of the
      binding energy depend on the charge of the AS polar heads as well as on the
      degree of electric interactions screening by the environment. At a certain
      optimal value of the screening coefficient, the energy of the system is the
      lowest (the most negative) and together with the rise in AS charge, the minimum
      of the energy moves towards its higher concentrations.

PMID- 12511966
TI  - Computer simulation studies on the significance of lipid polar head charge.
AB  - Ripple phase modelling was achievable by taking into consideration the dipole
      structure of the polar heads of model membrane molecules. Computer simulations
      enabled the selective analysis of a model membrane. Considering only the
      hydrophobic part of the lipid membrane, the gel-fluid transition stage can be
      obtained in such a simulation. Assuming an additional degree of freedom, the
      entire molecule can move along the normal to the membrane surface projected from
      two C-C bonds. The amounts of shifted lipids were 17% and 33% at temperatures of
      300 K (gel) and 330 K (fluid), respectively. Taking into account only polar head
      interactions in media of different ionic strength I, dielectric constant epsilon,
      and an effective charge and temperature, we could observe the same behaviour of
      the examined system independently of the values of I and ( when the charge was
      reduced to q/2. The amount of shifted heads at 300 K decreases sharply with the
      reduced charge value, with an accompanying increase in the number of "standing"
      polar heads. Summing up, it can be stated that hydrocarbon lipid chains exhibit a
      greater tendency to displacement in the fluid state than in the gel state.
      However, the polar heads behave in the opposite way: there are more displaced
      heads at 300 K than at 330 K. Thus, the overall analysis of the interactions
      between the molecules of the model membrane should enable us to find model
      parameters suitable for studying the lipid membrane at a wide range of
      temperatures. Finally, an electrostatic profile close to the membrane surface
      could be estimated in different membrane states. This should be useful in
      membrane-biologically active compound interaction analysis.

PMID- 12511967
TI  - Mechanistic approach to membrane mass transport processes (mini review).
AB  - Since the physical interpretation of practical Kedem-Katchalsky equations is not
      clear, we consider an alternative, mechanistic approach to membrane transport
      generated by osmotic and hydraulic pressure. We study a porous membrane with
      randomly distributed pore sizes (radii). We postulate that the reflection
      coefficient (sigma(p)) of a single pore may equal 1 or 0 only. From this
      postulate we derive new (mechanistic) transport equations. Their advantage is in
      clear physical interpretation.

PMID- 12511968
TI  - Alterations in cell nuclei during apoptosis.
AB  - Apoptosis is a genetically programmed phenomenon that aids in maintaining
      homeostasis in multicellular organisms. The characteristic morphological features
      of apoptosis are highly conservative and are dependent on the cell type and the
      apoptotic inducer. The nuclear events occurring during apoptosis include changes
      at the molecular level (i.e. DNA cleavage, modifications of nuclear polypeptides,
      and proteolysis of several proteins important for cell maintenance), and,
      consequently, alterations at the morphological level (i.e. chromatin
      condensation, nuclear shrinkage, DNA fragmentation and apoptotic body formation).
      These events are still not fully understood. It is very probable that a
      progressive decrease in pH could also be an essential factor for the induction of
      nuclease and protease activities, and an important element of the optimal
      conditions for their function. This review details the current state of knowledge
      on apoptotic nuclear events, with particular focus on the proteins involved in
      the execution of apoptosis in cell nuclei, and on the differences in substrate
      cleavage profiles for different types of cell undergoing cell death.

PMID- 12511969
TI  - The nuclear lamins and the nuclear envelope.
AB  - The cell nucleus is separated from the rest of the cell by the nuclear envelope.
      The nuclear envelope, nuclear envelope proteins and nuclear lamina organise the
      structure of the entire nucleus and the chromatin via a myriad of interactions.
      These interactions are dynamic, change with the change (progress) of the cell
      cycle, with cell differentiation and with changes in cell physiology.

PMID- 12511970
TI  - The isoform- and location-dependence of the functioning of the plasma membrane
      calcium pump.
AB  - The plasma membrane is a specialised multi-component structure with inter- and
      intracellular signalling functions. Ca2+ plays a crucial role in cellular
      physiology, and an ATP-driven plasma membrane calcium pump (PMCA) plays the
      greatest role in the maintenance of a low free Ca2+ concentration in the
      cytoplasm. The enzyme is coded by four separate genes (PMCA 1-4), and, due to
      alternative splicing, more than 20 variants can exist. PMCA 1 and 4 isoforms are
      present in almost all tissues, whereas PMCA 2 and 3 are found in more specialised
      cell types. The variants differ primarily in their regulatory regions, thus the
      modulation of calcium pump activity strongly depends on the isoform and the
      membrane composition. The unique function of PMCA isoforms was confirmed using
      the practical experimental models - a rat pheochromocytoma cell line, a human
      neuroblastoma cell line, or, more recently, knockout mice. In addition, based on
      the finding that PMCA could interact with several specific signaling proteins, it
      was concluded that its location in defined sites of the cell membrane could be a
      prerequisite for efficient intercellular communication.

PMID- 12511971
TI  - The role of focal adhesion kinase in the emigration of cells from confluent
      cultures.
AB  - We studied the effect of the modification of focal adhesion kinase (FAK) on the
      growth, migration and adhesion of C3H 10T1/2 cells. Cells transfected with
      plasmid coding for antisense FAK displayed a low level of FAK protein.
      Interestingly, the transfected cells achieved a higher saturation density at
      confluence, and displayed reduced adhesion and enhanced emigration from a
      confluent layer of cells when stimulated with fibronectin. In conclusion, it can
      be postulated that FAK plays an important role in the mechanism of contact
      inhibition.

PMID- 12511972
TI  - Effect of intramuscular application of selected neuropeptides on morphology of
      muscle.
AB  - The aim of the study was to examine a morphological picture of guinea pig
      skeletal muscles injected with neuropeptide Y (NPY), substance P (SP) or
      vasoactive intestinal peptide (VIP), to evaluate the influence of a single
      injection of the mentioned neuropeptides (NPS) on muscle morphology and mast
      cell, T lymphocyte and macrophage chemotaxis. There were different degrees of
      muscle fibre injuries as well as different intensities and compositions of
      infiltrations inside the muscle after the introduction of the NPS. The observed
      changes did not disappear, but increased after 24 hours, comparing to the 3-hour
      post-injection changes, suggesting that NPS are proinflammatory rather than
      antiinflammatory factors in skeletal muscles. The local, particularly delayed
      action of NPS in vivo requires further studies.

PMID- 12511973
TI  - Reactive oxygen species upregulate expression of PAI-1 in endothelial cells.
AB  - Second messengers involved in the signal transduction pathway leading to
      induction of the plasminogen activator inhibitor (PAI-1) have not yet been well
      characterized. This study focuses on the mechanisms of regulation of PAI-1
      expression by reactive oxygen species (ROS) in human endothelial cells.
      Inhibition of the tumor necrosis factor alpha (TNFalpha?-induced expression of
      PAI-1 by antioxidant N-acetyl-L-cysteine (NAC) indicated redox-sensitive
      mechanisms involved in the signaling pathway. Because TNFalpha induces PAI-1
      production in endothelial cells, and NAC attenuated this response, we attempted
      to investigate the possible involvement of ROS in the activation of PAI-1 by
      TNFalpha. Upregulation of PAI-1 expression in endothelial cells by the
      stimulation with TNFalpha (50 ng/ml) or H2O2 (10-200 micro M), observed by
      measurement of the antigen and mRNA levels, was reversed in the presence of NAC
      (20mM). The stimulatory effect of ROS was detected also at the level of the PAI-1
      promoter in endothelial cells transfected with plasmid p800 LUC containing a PAI
      1 promoter fragment (+71 to -800). The PAI-1 promoter activity was increased in
      the presence of ROS, and was suppressed by up to 75% in the presence of
      antioxidants. On the basis of this study we can conclude that reactive oxygen
      species play an important role in a cytokine-induced activation of PAI-1
      expression, and may act as a signal transduction messenger.

PMID- 12511974
TI  - Dynamin: characteristics, mechanism of action and function.
AB  - Dynamin - a member of the GTP-ase protein family - is essential for many
      intracellular membrane trafficking events in multiple endocytic processes. The
      unique biochemical features of dynamin - especially its propensity to assemble -
      enable severing the nascent vesicles from the membrane. The mechanism of
      dynamin's action is still a subject of debate - whether it functions as a
      mechanochemical enzyme or a regulatory GTPase. The GTPase domain of dynamin
      contains three GTP-binding motifs. This domain is very conservative across the
      species, including that recently cloned by us in the unicellular eukaryote
      Paramecium. Dynamin interacts with a number of partners such as endophilin and
      proteins involved in coordination of endocytosis with motor molecules. A growing
      body of evidence indicates that dynamin and dynamin-related proteins are involved
      both in pathology and protection against human diseases. The most interesting are
      dynamin-like Mx proteins exhibiting antiviral activity.

PMID- 12511975
TI  - Thioridazine induces erythrocyte stomatocytosis due to interactions with
      negatively charged lipids.
AB  - Despite the fact that thioridazine is used clinically as a neuroleptic drug,
      little is known about the molecular mechanisms underlying its biological effects,
      in particular about its interactions with membranes. In the present work we
      investigate the influence of thioridazine on model and cell membranes, using
      calorimetry, DPH fluorescence polarization measurements, studies of haemolysis
      and scanning electron microscopy. The experiments show that thioridazine
      interacts with lipid bilayers and intercalates into bilayer structure. We found
      that erythrocyte stomatocytosis induced by the drug might be related to
      preferential interaction of thioridazine with charged lipids.

PMID- 12511976
TI  - The interaction of tryptophan and ANS with PAMAM dendrimers.
AB  - Dendrimers are globular, hyperbranched polymers possessing a high concentration
      of surface functional groups and internal cavities. These unique features make
      them very useful in many biomedical applications, especially as carrier
      molecules. In this study, the interaction of tryptophan and 1-anilinonaphthalene
      8-sulfonic acid with three types of polyamidoamine dendrimers was examined. It
      was observed that the type of dendrimer surface group has a strong impact on the
      interactions between the dendrimers and fluorescent molecules.

PMID- 12511977
TI  - The influence of membrane lipid metabolites on lymphocyte potassium channel
      activity.
AB  - In the present study, the whole-cell patch-clamp technique was applied to
      elucidate modulatory effects of high-density lipoproteins (HDL), sphingosine
      (SPH), sphingosine-1-phosphate (SPP), lysophosphatidic acid (LPA) and sphingosyl-
      phosphorylcholine (SPC) on the activity of Kv1.3 channels in human T lymphocytes
      (TL). Obtained data provide evidence that application of SPC at micromolar
      concentrations shifts the channel activation midpoint by about 20 mV towards
      positive membrane potentials. This effect occurs in a concentration-dependent
      manner and is saturated at SPC concentrations higher than 10 micro M. The shift
      of channel activation midpoint is accompanied by a pronounced slowing of the
      activation kinetics. The modulatory effect of SPC is clearly voltage-dependent,
      being most potent at -20 mV and least potent at +60 mV. The steady-state
      inactivation curve is also shifted by about 20 mV towards positive membrane
      potentials. The kinetics of channel inactivation and deactivation (closure)
      remain unaffected upon SPC treatment. In contrast, application of HDL (250 micro
      g/ml), SPH (50 and 100 micro M), SPP (10 micro M) and LPA (10 and 36 micro M)
      does not exert any modulatory effect on the channel activity. The effect of SPC
      on Kv1.3 channel gating resembles the effect exerted by extracellular zinc at the
      concentration of 10 micro M. It is concluded that the effect of SPC is specific
      and may be due to the presence of a choline residue in SPC molecules. The
      possible mechanism and the physiological significance of this modulatory effect
      on Kv1.3 channels are discussed.

PMID- 12511978
TI  - The effects of growth regulators on somaclonal variation in rye (Secale cereale
      L.) and selection of somaclonal variants with increased agronomic traits.
AB  - The aim of this research was to characterize somaclonal variation in populations
      derived from embryos cultured on two types of induction medium (supplemented with
      either 2,4-D or dicamba), as well as to select and characterize several
      somaclonal lines. The sexual progenies of 40 R(0)regenerants - A somaclones
      (derived on the medium with 2,4-D) and B somaclones (derived on the medium with
      dicamba) - were analysed according to the following traits: plant height, total
      number of tillers, number of productive tillers, spike length, number of
      spikelets per spike, spike compactness, number of normally developed grains per
      spike, weight of grains per spike, and the weight of 1000 grains. The results for
      twenty-two R(1)plants surpassed the variability range for the control. The
      transmission of positive changes to the next generation was proved in the case of
      8 originally chosen R(1) plants: 7 plants selected from the A somaclones and one
      plant from the B somaclones. Five out of the eight created somaclonal lines
      proved to be stable somaclonal variants. The absolute rate of the efficiency of
      positive somaclonal changes was calculated as 0.64%.

PMID- 12511979
TI  - Lysosomotropic N,N- dimethyl alpha-aminoacid N-alkyl esters and their quaternary
      ammonium salts as plasma membrane and mitochondrial ATPases inhibitors.
AB  - A set of n-alkyl esters of N,N-dimethylglycine (DMG-n) and their methobromides
      (DMGM-n) was synthesized, and their activities on yeast Saccharomyces cerevisiae
      were compared. The compounds differ in the number of carbon atoms in the
      aliphatic chain. Aminoesters with 12 carbon atoms appeared to be most active.
      Unlike quaternary ammonium salts previously tested, the activities of the
      compounds were not pH-dependent; the minimal inhibitory concentrations (MIC) were
      identical at pH 8 and at pH 6. In contrast to quaternary ammonium salts,
      aminoesters showed similar effects on respiratory sufficient (rho+) and
      respiratory deficient (rho0) mutants. When tested on glucose stimulated proton
      extrusion, aminoesters applied at MIC increased external pH. Aminoesters
      inhibited the plasma membrane H+-ATPase, whereas they were less inhibitory on the
      mitochondrial ATPase. In order to further compare the aminoesters and their
      corresponding quaternary ammonium salts, derivatives of N,N-dimethylalanine (DMAL
      n and DMALM-n, respectively) were synthesized. The quaternary ammonium salts
      appeared to have a higher inhibitory potency than aminoesters, especially at pH
      8, and alanine derivatives inhibited growth at a lower concentration than glycine
      derivatives. Both alanine derivatives of the aminoester and the quaternary
      ammonium salt inhibited the plasma membrane H+- ATPase at lower concentrations
      than glycine derivatives, but the alanine aminoester was without a detectable
      effect on the mitochondrial ATPase.

PMID- 12511980
TI  - The adjuvant activity of lactoferrin in the generation of DTH to ovalbumin can be
      inhibited by bovine serum albumin bearing alpha-D-mannopyranosyl residues.
AB  - Lactoferrin (LF) is an iron-binding glycoprotein present in the cytoplasmic
      granules of neutrophils and in external secretions of mammals. Although the
      biological role of human and bovine lactoferrin has been extensively studied,
      there is still uncertainty as to the nature and function of lactoferrin
      receptors. We recently determined that methyl-alpha-D-mannopyranoside given
      intraperitoneally (i.p.) could suppress the adjuvant activity of LF in the
      generation of delayed-type hypersensitivity (DTH) to ovalbumin (OVA). We
      concluded that the lactoferrin effects in DTH are mediated by carbohydrate
      recognizing receptors like the mannose receptor (MR). This study indicates that
      subcutaneous (s.c.) administration of very small doses of the Man-bovine serum
      albumin (Man-BSA) complex, together with a sensitizing dose of the antigen, gives
      the same effects as i.p. administration of methyl-alpha-D-mannopyranoside. The
      latter is also a blocker of MR, although of a much lower affinity to the receptor
      than Man-BSA. The blocking of the adjuvant effect of LF by the Man-BSA complex
      (when given together with the sensitising dose of antigen) suggests that the
      function of antigen-presenting cells in the skin (presumably immature dendritic
      cells expressing MR) is inhibited. The results of our study indicate that a
      receptor with an affinity for mannose is essential for the mediation of adjuvant
      lactoferrin function in the generation of DTH.

PMID- 12511981
TI  - The role of cell wall in plant embryogenesis.
AB  - This review presents recent data about cell wall involvement in plant
      embryogenesis. During plant development, the cell wall is subjected to precise
      regulation. During this process a bidirectional information exchange between the
      cell wall and the protoplast is observed. The cell wall also mediates in the cell
      cell (apoplastic) and cell to cell (symplastic) information flow. Especially some
      products derived from the hydrolysis of specific cell wall compounds can act as
      short distance signal transduction molecules during the development.
      Oligosaccharins are a group of such products. Their activity and sources focused
      the researchers' attention on the biochemical composition of the cell wall and
      the activity of some cell wall enzymes. The dramatic influence on the embryo body
      shape has also the cell wall synthesis machinery, including vesicular secretion
      pathways. Moreover, the interplay between the turgor pressure and counteracting
      cell walls and neighbouring cells (in higher organisms) creates the specific
      mechanical forces influencing the development of the whole plant. We conclude
      that discovering factors which can influence cell wall physiology and
      architecture is crucial for a better understanding of plant embryogenesis. In
      this review we summarize some recent experimental data reporting plant cell wall
      involvement in embryogenesis, putting special emphasis on somatic embryogenesis.

PMID- 12511982
TI  - Natriuretic peptides reduce plasminogen activator inhibitor-1 expression in human
      endothelial cells.
AB  - Plasma concentrations of natriuretic peptides increase in some pathological
      conditions, but very little is known about the effect of these vasodilator
      peptides on the regulation of the blood coagulation system. The fundamental role
      in the regulation of fibrinolysis is played by plasminogen activator inhibitor
      type 1 (PAI-1). Recent studies demonstrate that natriuretic peptides can modulate
      PAI-1 expression in bovine aortic smooth muscle cells and rat aortic endothelial
      cells. In this report, we tested the effect of natriuretic peptides on PAI-1
      expression in the human endothelial cell line (EA.hy 926). For this purpose, we
      treated the cell cultures with ANP, BNP and CNP, and modulation of PAI-1
      synthesis was evaluated. We compared the effect of natriuretic peptides on
      synthesis and release of PAI-1 in unstimulated cells, and after activation with
      tumour necrosis factor alpha (TNFalpha). Natriuretic peptides abolished TNFalpha 
      induced upregulation of PAI-1 expression at both the PAI-1 mRNA and the antigen
      levels. The inhibitory efficiency was higher in the case of CNP when compared to
      that produced by ANP and BNP, particularly when TNFalpha-stimulated cells were
      used. We observed an inhibition of stimulatory effect of TNFalpha on PAI-1
      expression also at the level of the PAI-1 promoter in cells transfected with a
      PAI-1 promoter fragment (+71 to -800). The PAI-1 promoter activity was markedly
      inhibited by C-type natriuretic peptide, already at a very low (0.001 micro M)
      concentration of the peptide.

PMID- 12511983
TI  - Role of membranotropic effects of glucocorticoids in the realization of their
      pharmacological activity.

PMID- 12511984
TI  - Cycloheximide prevents inhibition of expression of immediate early gene c-fos in
      paraventricular nuclei of rat hypothalamus produced by delta sleep-inducing
      peptide.
AB  - We studied expression of the immediate early gene c-fos in hypothalamic
      paraventricular nuclei in rats with different prognostic resistance to emotional
      stress receiving delta-sleep-inducing peptide after intracerebroventricular
      administration of cycloheximide. Delta-sleep-inducing peptide inhibited
      expression of the c-fos gene in rats receiving intracerebroventricular injection
      of physiological saline. Pretreatment with the protein synthesis blocker
      cycloheximide abolished changes produced by delta-sleep-inducing peptide.

PMID- 12511985
TI  - Ultrastructural changes in myocardium of hypertensive rats treated with
      nifedipine.
AB  - Spontaneously hypertensive rats (SHR) with high systolic pressure received
      calcium antagonist nifedipine in medium therapeutic doses for 2 weeks. Electron
      microscopy of the myocardium revealed considerable changes in the sarcoplasmic
      reticulum manifested in dramatic dilation of tubules, destruction of membranes,
      and appearance of amorphous matter of medium electron density in tubules in
      animals treated with nifedipine. Since sarcoplasmic reticulum plays an important
      role in calcium-dependent excitation-contraction coupling, the observed
      structural changes can underlie the negative inotropic effect of long-term
      nifedipine therapy.

PMID- 12511986
TI  - Mechanisms of changes in the hemoglobin profile during acute adaptation to
      extreme conditions.
AB  - We studied changes in rat hemoglobin isoforms during acute adaptation to various
      hypoxic conditions. Erythrocytes were heterogeneous in the content of various
      hemoglobin isoforms. Changes in the hemoglobin profile during hypoxia are related
      to variations in the ratio between populations of erythrocytes differing in the
      content of individual hemoglobin isoforms.

PMID- 12511987
TI  - Changes in phospholipid composition of synaptic membranes in medulla oblongata
      and frontal lobes of the cerebral hemispheres in cats with hemorrhagic shock.
AB  - We studied phospholipid composition of brain synaptic membranes isolated from
      cats with severe hemorrhagic shock. Changes in the medulla oblongata were most
      pronounced and manifested in decreased content of phosphatidylcholine. Changes in
      the phospholipid composition of synaptic membranes in the frontal lobes included
      an increase in phosphatidylinositol content and reduced content of
      phosphatidylserine. Accumulation of phosphatidylethanolamine in synaptic
      membranes was found in both the medulla oblongata and frontal lobes. These data
      help to understand the mechanisms underlying exhaustion of compensatory reserves
      in brain cells during severe hemorrhagic shock.

PMID- 12511988
TI  - Effect of Maksar on antioxidant system in rats with type IIa alimentary
      hyperlipoproteinemia.
AB  - The development of type IIa alimentary hyperlipoproteinemia in rats was
      accompanied by changes in activity of glutathione-dependent enzymes, exhaustion
      of the reserves of antioxidant vitamins in the liver and blood, and
      intensification of lipid peroxidation. The hepatoprotective preparation Maksar
      obtained from far-eastern plants Maachia amurensis and containing natural
      biological antioxidants normalized blood lipid composition, corrected liver
      lipidosis, and improved the antioxidant defense system.

PMID- 12511989
TI  - Effect of capsaicin on dynamics of neutrophil functional activity in Wistar rat
      venous blood.
AB  - Capsaicin in neurotoxic dose produced phasic changes in functional activity of
      sensory neuropeptides and venous blood neutrophils of Wistar rats. At the early
      terms after capsaicin injections, the sensitivity of neutrophils to bacterial
      stimuli decreased against the background of neuropeptide release from the sensory
      terminals. After 2 weeks, activity of neutrophils assessed by NBT-test increased
      against the background of depletion of neuropeptide stores, while total
      antioxidant activity of venous plasma decreased. On day 21 of capsaicin
      treatment, when the content of neuropeptides returned to the baseline level,
      functional activity of neutrophils decreased and plasma antioxidant activity
      returned to the control level.

PMID- 12511990
TI  - Expression of beta-Secretase mRNA in the brain of rats with immunohistochemical
      destruction of basal forebrain cholinergic system.
AB  - We studied properties of cloned BACE mRNA (beta-site of the enzyme cleaving
      amyloid precursor protein) and evaluated the possibility of using this clone for
      identification and/or prediction of neurodegenerative disorders associated with
      cholinergic deficiency. Wistar rats subjected to immunohistochemical destruction
      of the basal forebrain cholinergic system were used as the experimental model.
      Nonradioactive in situ hybridization and immunohistochemical visualization of the
      astroglia revealed strong hybridization signal of BACE mRNA in neurons of the
      cortex, hippocampus, and thalamus. Astrocytes remained unstained.
      Immunohistochemical destruction of the basal forebrain produced no significant
      changes in the distribution of BACE mRNA.

PMID- 12511991
TI  - Changes in lymph microcirculation during pathological stress.
AB  - Stress caused by immobilization and acoustic stimulation produces considerable
      changes in lymph microcirculation. These changes manifested in dilation of
      microvessels, enhanced phasic contractile activity and its abnormal pattern,
      accelerated lymph flow, and recruitment of new lymphangions in drainage
      functions.

PMID- 12511992
TI  - Effects of lipid peroxidation on structure of human plasma lipoproteins (magnetic
      resonance spectroscopy).
AB  - Magnetic resonance spectroscopy revealed structural modifications of human plasma
      lipoproteins during peroxidation induced by copper sulfate in vitro. Decreased
      molecular mobility of fatty acid chains in lipoprotein lipids was demonstrated.

PMID- 12511993
TI  - Effect of bioresonance therapy on antioxidant system in lymphocytes in patients
      with rheumatoid arthritis.
AB  - We measured activities of superoxide dismutase, catalase, and glutathione
      peroxidase and content of nonprotein thiol groups (reduced glutathione) in blood
      lymphocytes from patients with rheumatoid arthritis before and during
      bioresonance therapy. The state of the antioxidant system in lymphocyte from
      patients receiving standard pharmacotherapy was characterized by activation of
      the key antioxidant enzymes and decreased content of thiol groups. Bioresonance
      therapy increased the content of thiol groups and normalized activities of
      superoxide dismutase and glutathione peroxidase. However, catalase activity
      remained above the control. Changes in the lymphocyte antioxidant system indicate
      that bioresonance therapy activates nonspecific protective mechanisms in patients
      with rheumatoid arthritis.

PMID- 12511994
TI  - Activity of phospholipase A2 with different localization in liposomes.
AB  - Damages to liposomal membranes resulted from intensification of lipid
      peroxidation with iron ions in the presence of ascorbate or treatment with the
      membrane disintegrator tetrachloromethane led to activation of phospholipase A2,
      which depended on the enzyme localization in liposomes. Activity of phospholipase
      A2 located on the inner liposome surface increased less significantly compared to
      the enzyme bound to the outer surface.

PMID- 12511995
TI  - Biokinetics of transdermal 3-hydroxyphenazepam.
AB  - The kinetics of labeled 3-hydroxyphenazepam (active phenazepam metabolite) after
      its intravenous and transdermal administration was studied. Biphasic kinetic of
      drug distribution in the organism was revealed; pharmacokinetic parameters and
      biological availability (1.32  0.12 for the plasma and 1.21 0.10 for the brain)
      were determined on the basis of total radioactivity of the plasma and brain.

PMID- 12511997
TI  - Effect of vitamin therapy on sensitivity of peripheral blood lymphocytes to
      clastogenic effect of mutagens in vitro.
AB  - Spontaneous and in vitro induced (with 0.01 and 0.1 mg/ml dioxidine and 0.1 and
      1.0 U/ml bleomycin) chromosome aberrations were counted in cultured peripheral
      blood cells from 11 donors before and after 2-week therapy with a vitamin
      complex. The complex contained the major vitamins in doses not surpassing the
      recommended daily doses. Vitamins had no effect on spontaneous mutations, but
      increased cell resistance to clastogenic effects of dioxidine in a concentration
      of 0.1, but not 0.01 mg/ml. Cell sensitivity to bleomycin notably increased after
      vitamin therapy in some donors and decreased in others, the mean parameters in
      the group remained virtually unchanged.

PMID- 12511996
TI  - Effect of panangin on activity of messengers systems in hypertrophied rat
      myocardium.
AB  - The balance between the two major second messenger systems in hypertrophied
      myocardium was studied in rats receiving panangin for 16 days. Panangin producing
      stimulating and polarizing effects on cardiomyocyte membrane improved
      electrophysiological characteristics of hypertrophied myocardium (electrical
      stability, duration of supernormal excitability period, and action potential),
      activated the phosphoinositide exchange, and inhibited the adenylate cyclase
      system. The panangin-induced change in membrane potentials was accompanied by a
      pronounced inositol response, i.e. a decrease in the content of membrane
      polyphosphoinositides (phosphatidylinositol-4-phosphate and phosphatidylinositol
      4,5-biphosphate) in the brain. It was concluded that function of ion channels
      depends on activity of phosphoinositide- and adenylate cyclase second messengers
      systems.

PMID- 12511998
TI  - Halonal is a phenobarbital inductor of the monooxygenase system.
AB  - Experiments on rats demonstrated induction of the hepatic monooxygenase system
      with halonal. The effects of halonal and phenobarbital on the contents of
      cytochrome P-450 and its isoform P-450b+e and on the rate of substrate metabolism
      were similar. This suggests that enzyme-inducing activity of halonal is
      determined by the effect of its major metabolite. It cannot be excluded that
      halonal molecules possess intrinsic enzyme-inducing activity.

PMID- 12511999
TI  - Possible involvement of neurokinin receptors in CNS and neuromuscular synapse in
      the realization of the effects of CAPAH and substance P.
AB  - Nootropic non-anticholinesterase organophosphorus preparation CAPAH and substance
      P produced similar and dose-dependent effects on the amplitude and temporal
      parameters of miniature endplate potentials in mammalian neuromuscular synapse.
      Neurokinin receptor antagonist Win-51.708 abolished the effects of these agents.
      In behavioral experiments substance P moderated the mnemotropic and
      antidepressant effects of CAPAH. It was assumed that neurokinin receptors are the
      targets of CAPAH and substance P in CNS and neuromuscular synapse.

PMID- 12512000
TI  - Efficiency of enzyme-inducing agents in rats with intrahepatic cholestasis.
AB  - Inductors of the monooxygenase system benzonal, halonal, and halodif prevented
      the development of intrahepatic cholestasis induced by a-naphthylisothiocyanate
      and stimulated detoxifying function of the liver in rats. These agents increased
      the content of microsomal protein and cytochrome P-450 and accelerated metabolism
      of types I and II substrates. This was accompanied by a decrease of serum
      concentrations of total and free bilirubin and activity of liver-specific
      enzymes. Phenobarbital did not prevent the development of hepatocyte cytolysis.

PMID- 12512001
TI  - Modulation of orientation and exploratory behavior of (CBAxC57Bl/6)F1 mice by
      immunocompetent cells.
AB  - The present investigation develops a previously published concept on integration
      of the immune, endocrine, and nervous systems in a universal structural and
      functional block (IMEN system). Splenocytes from donor (CBAxC57Bl/6)F1 mice
      characterized by specific behavior in the open field test modified the behavior
      of syngeneic recipient mice after intravenous infusion.

PMID- 12512002
TI  - Adhesion of Staphylococcus aureus to implants with different physicochemical
      characteristics.
AB  - Adhesion of pathogenic Staphylococcus aureus (strain 209) to BT1-0 titanium disks
      (12 mm in diameter) with different coatings and noncoated was studied in vitro by
      photocolorimetry. Transparency of bacterial suspension in normal saline was
      evaluated after 2-h culturing with the implants at 37 degrees C. The decrease of
      S. aureus content in the suspension due to its adsorption on implants was
      negligible and increased by 0.9-5.5% in comparison with the control (adhesion to
      glass). When the specimens were placed into bacterial suspension, the density of
      staphylococcal adsorption on the surface considerably increased (by 9-53%) in
      comparison with the control, which attested to active participation of the
      implants in bacterial adsorption. The degree of bacterial adhesion to the
      implants decreased in the following order: disk with calcium phosphate ceramic
      coating-disk with calcium phosphate X-ray amorphous coating-disk without coating
      disk with cermet coating. The adhesion of Staphylococcus is a stochastic process
      depending on the sum of implant characteristics, in particular, on the phase
      composition of the coating, electric conductivity, and Ca/P ionic ratio. The
      authors conclude that the formation of antibacterial properties of coating by
      saturating them with antibiotics or impregnation with metals, specifically silver
      ion implantation, is justified, because it reduces the postimplantation infection
      risk.

PMID- 12512003
TI  - Effect of configuration of muramyl dipeptide glycoside bond and structure of
      glycoside aglycon on their capacity to stimulate production of interleukin-1 and
      tumor necrosis factor by macrophages.
AB  - Effects of 11 original glycoside derivatives of muramyl dipeptide on the
      production of interleukin-1 and tumor necrosis factor by mouse peritoneal
      macrophages were studied. The relationship between macrophage activation
      evaluated by induction of these cytokines and configuration of glycoside bond and
      aglycon structure of MDP was revealed.

PMID- 12512004
TI  - Tick-borne typhus fever of northern Asia: some characteristics of the
      pathogenesis.
AB  - Morphological changes in the viscera of albino mice were studied over the course
      of North Asia typhus fever. In general, the microcirculatory bed in the studied
      organs (brain, liver, spleen, peritoneum, and testicle) corresponded to
      angioparalytical capillary and venular hyperemia. Macrophagic reaction
      (proliferation of stellate macrophages) transformed into granulomatous reaction
      in the course of the experiment. Macrophagic reaction of the spleen was
      characterized by blurred follicular pattern. In the testes a tendency to the loss
      of normal spermatogenesis was observed.

PMID- 12512005
TI  - Effect of hyperlipidemia on functional activity of peritoneal macrophages in CBA
      and C57Bl/6 mice.
AB  - The effect of experimental hyperlipidemia on functional activity of macrophages
      was studied in CBA and C57Bl/6 mice resistant and sensitive to the formation of
      aorta lesions, respectively. Two-month atherogenic diet increased the content of
      cholesterol in the serum and cells of peritoneal exudate in mice of both strains.
      In parallel, production of nitrites and 5'-nucleotidase activity in peritoneal
      macrophages increased, while parameters of phagocytosis, pinocytosis, and NBT
      test remained unchanged. Changes in the state of macrophages can be explained by
      increased cholesterol content. The absence of differences in functional activity
      of macrophages in CBA and C57Bl/6 mice indicates that the observed shifts are
      insignificant for the development of fatty streaks in the aorta.

PMID- 12512006
TI  - Cardioprotective effect of energostim during occlusion of coronary artery.
AB  - Experiments on dogs showed that energostim, a directly acting antihypoxant,
      injected 15 min after occlusion of the upper one-third of the left descending
      branch of the interventricular coronary artery produced a pronounced
      cardioprotective effect. The effect was confirmed by electron microscopy
      (evaluation the necrotic focus), biochemical tests of the heart and blood, and
      changes in intracardiac hemodynamics (recovery of systolic and diastolic
      functions). The cardioprotective effect of energostim greatly surpasses that of
      routine therapy applied during acute myocardium infarction.

PMID- 12512007
TI  - Detection of Campylobacter jejuni in healthy monkeys and monkeys with enteric
      infections by PCR.
AB  - Campylobacter were detected by PCR in feces of monkeys of different species
      (clinically healthy, with diarrhea, and dead from acute enteric infections). High
      prevalence of these bacteria in monkeys was revealed. The incidence of C. jejuni
      DNA in monkeys with acute enteric infections was higher than in healthy animals
      (69.6 and 51.3%, respectively). The highest percentage (92.3) of positive results
      was observed in Macaca mulatta with enteric diseases and in macaque dead of these
      diseases. The presence of C. jejuni in monkeys with diarrhea and the absence of
      pathogenic enterobacteria (Shigella, Salmonella, Yersinia) in feces probably
      attest to etiological relationship of acute enteric infections with
      Campylobacter.

PMID- 12512008
TI  - Biosynthetic reactions and ultrastructure of urothelial cells in chronic cystitis
      and cystopathies.
AB  - A new form of morphogenesis of pathological process, cystopathy, was
      distinguished on the basis endoscopy data and morphofunctional analysis of the
      urinary bladder in chronic cystitis. Cystopathy is characterized by predominance
      of diffuse degeneration and atrophy of the urothelium, stromal sclerosis, absence
      of inflammatory cell infiltration, and inhibition of biosynthetic reactions in
      urothelial cells (compared to chronic cystitis). Cystopathy results from
      regeneratory and plastic failure. Instability of the bladder epithelium can be a
      morphological marker of oncological risk.

PMID- 12512009
TI  - Immunohistochemical, molecular, and pathomorphological study of liver biopsy
      specimens during chronic hepatitis C.
AB  - We carried out a comparative study of replication markers of hepatitis C virus
      (HCV RNA) in some biological substrates and NS3-antigen in liver biopsy
      specimens. It was found that 82% liver specimens contained RNA HCV, in 44% cases
      HCV RNA was present in the serum, mononuclear blood cells, and liver. The
      presence of NS3-antigen in hepatocytes can be considered as a structural marker
      of HCV replication, which is confirmed by positive correlation with the results
      of PCR for viral RNA in tissue specimens. In most cases the presence of HCV
      replication markers did not correlate with activity of the infectious process
      assessed by biochemical and histological tests.

PMID- 12512010
TI  - In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract
      of Capparis spinosa L buds.
AB  - The aim of the present study was to evaluate the in vitro antioxidant and in vivo
      photoprotective activities of a lyophilized extract of Capparis spinosa L. (LECS)
      obtained by methanolic extraction from the flowering buds of this plant. For the
      in vitro experiments, LECS was tested employing three different models: (a).
      bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test); (b).
      peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2
      amidinopropane) hydrochloride, of mixed dipalmitoylphosphatidylcholine/linoleic
      acid unilamellar vesicles (LUVs) (LP-LUV test); and (c). UV-induced peroxidation
      of phosphatidylcholine multilamellar vesicles (UV-IP test). The in vivo
      antioxidant/radical scavenger activity was assessed by determining the ability of
      topically applied LECS to reduce UVB-induced skin erythema in healthy human
      volunteers. From the results obtained in in vitro and in vivo tests, LECS showed
      a significant antioxidant effect. Furthermore, by chromatographic fractionation
      and spectroscopic methods, we identified the major constituents of LECS, and
      particularly some flavonols (kaempferol and quercetin derivatives) and
      hydroxycinnamic acids (caffeic acid, ferulic acid, p-cumaric acid, and cinnamic
      acid).

PMID- 12512011
TI  - Labile proteins accumulated in damaged hair upon permanent waving and bleaching
      treatments.
AB  - We previously found that certain hair proteins were soluble by means of a partial
      extraction method. In this study, we demonstrate that the amount of soluble
      proteins internally formed in permed and bleached hair, labile proteins, is a
      useful index for hair damage assessment. Compared to tensile property changes,
      this index rose in widely dynamic ranges as the time of either permanent waving
      or bleaching treatments increased. The amount of labile proteins was much larger
      than that of proteins eluted into perming and bleaching lotions. However, the
      labile proteins showed electrophoretic profiles similar to those of the eluted
      proteins. These results suggest that a portion of the stable proteins in normal
      hair was transformed into labile proteins upon permanent waving and bleaching
      treatments. Consequently, permed and bleached hair tends to release the resultant
      labile proteins.

PMID- 12512012
TI  - Mechanical analysis of elasticity and flexibility of virgin and polymer-treated
      hair fiber assemblies.
AB  - The elasticity and flexibility of virgin and polymer-treated hair fiber
      assemblies were investigated by employing straight hair tresses or hair shaped
      into omega loops. Polymer treatment was accomplished by saturating fibers with
      polymeric solutions, resulting in a deposition of 10-90 mg of polymer per gram of
      hair. The mechanical testing procedure consisted of subjecting omega-loop-shaped
      hair or straight hair tresses to multiple bending deformations at 25% strain in a
      texture analyzer. A total of ten deformations were typically carried out, and
      elasticity or flexibility parameters were evaluated from data such as (a). the
      force at 8% deformation, i.e., within the elastic region of bending deformation
      for hair shaped into an omega loop, (b). maximum force in the first (F(1)) and
      tenth (F(10)) deformation cycles, (c). elastic modulus in the first (E(1)) and
      tenth (E(10)) deformation cycles, and (d). the change in hair sample dimensions
      between the first (H(1)) and tenth (H(10)) deformation cycles. Parameters such as
      stiffness ratio (1), F(10)/F(1), E(10)/E(1), and H(10)/H(1) were employed to
      characterize hair tress rigidity, flexibility or resistance to breakage, and
      plasticity. Untreated hair was found to be almost perfectly elastic and flexible
      at 50% RH, evident by the linear dependence of force vs deformation. Flexibility
      parameters F(10)/F(1), E(10)/E(1), and H(10)/H(1) were in the range of 0.95 to
      1.0 at low humidity, while the parameters F(10)/F(1) and E(10)/E(1) and were 10%
      lower at 90% RH. Examination of polymer-modified hair allowed for classification
      of treatments into categories termed brittle, quite flexible and nonplastic,
      flexible and plastic, very flexible and very plastic, and very flexible and
      nonplastic. Poly(vinyl pyrrolidone) is shown as an example of a quite flexible
      and nonplastic material, with its flexibility and stiffness dependent upon its
      molecular weight. The effect of plasticizers on polymer behavior is also
      discussed.

PMID- 12512013
TI  - The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model
      active ingredient.
AB  - Phospholipids or liposomes are recognized to have skin permeation enhancing
      ability, although their mechanisms are still controversial. The aim of this study
      was to establish a method of increasing the skin permeation of active
      ingredients, using phosphatidylcholine as a permeation enhancer. Caffeine was
      used as a model active ingredient and in vitro skin penetration experiments were
      performed using Franz-type diffusion cells to determine the amount of absorbed
      caffeine. Lipid vesicles were prepared by the microfluidization process. The
      encapsulation efficiency of caffeine was found to be very low due to the
      instability of the liposome structure and the water solubility of caffeine.
      However, the amount of absorbed caffeine was nearly independent of the
      encapsulation efficiency and the vesicle size, but increased with the increase of
      phosphatidylcholine concentration. These results indicated that
      phosphatidylcholine could act as a penetration enhancer, irrespective of its
      presence in vesicular form or solubilized form.

PMID- 12512014
TI  - Stability and release of topical tranexamic acid liposome formulations.
AB  - Tranexamic acid (TA) has been claimed to have whitening effects. The effects of
      TA contents (5% and 10%) and charges on the stability and release of TA entrapped
      in hydrogenated soya phosphatidylcholine/cholesterol/charged lipid [dicetyl
      phosphate (-) or stearylamine (+)] liposomes at molar ratios of 7:2:1(-) and
      7:2:1 (+) were investigated. The TA contents were determined
      spectrophotometrically at 415 nm, following derivatization with 2,4,6
      trinitrobenzosulfonic acid. Stability and leakage of TA from liposomes were
      characterized at 4 degrees, 30 degrees and 45 degrees C for 90 days. The leakage
      rates of TA in negative liposomes were lower than those in positive liposomes.
      The TA in all liposome formulations was relatively stable, as > 90% of total drug
      remained after up to two months. The release of TA from liposomes was examined
      using vertical Franz diffusion cells at 37 degrees C for 24 h. The release rates
      of TA from all liposome formulations were approximately 3 times lower than those
      from solutions. Charges appeared to affect the physical stability, leakage, and
      shelf life of TA in liposomes, whereas TA concentrations seemed to affect the
      release of TA. The 7:2:1 (10% TA,-) liposome was the best formulation, due to its
      small size, low leakage, high stability, and prolonged and sustained release
      profile.

PMID- 12512015
TI  - Influence of internal structure of hair fiber on hair appearance. II.
      Consideration of the visual perception mechanism of hair appearance.
AB  - The optical properties of hair fibers were studied, focusing on the reflections
      (highlights) from both the front and the back surfaces of the fiber in
      consideration and on the effect these have on the perceptions of hair appearance.
      The two reflections are distinguished from each other by sight, because only the
      back surface reflection is colored by melanin granules and/or dyestuffs inside
      the fiber. When we observe a flat plate as a model for hair without a cuticle
      structure, the visual angle between the two light loci correlates with the
      thickness of the model plate and gives an impression of depth. In the case of
      hair with a cuticle angle, the visual angle is maintained even when the fiber
      thickness is reduced. This visual angle causes an overestimation of the thickness
      and enhances the impression of depth. The visual angle changes dramatically with
      a curl curvature change of the hair tress, meaning that the impression of depth
      is also dynamically changed by a small change in hairstyle. The dynamic change in
      the impression of depth probably causes a vibrant impression. The following are
      required for beautiful hair appearance along with an impression of depth and
      vibrancy: (a). Internal structure without light scattering origins is essential
      to observe vivid colored highlights from the back surface. (b). Well-ordered
      cuticles are essential to get intensive double highlights from the front and back
      surfaces. (c). A properly curved hairstyle is essential to obtaining a more
      vibrant impression.

PMID- 12512020
TI  - HIPAA privacy guidelines effective in April.

PMID- 12512021
TI  - The "organification" of functional GI disorders: implications for research.

PMID- 12512022
TI  - Lieberkuhn of the crypts of Lieberkuhn.

PMID- 12512023
TI  - Image of the month: giant fibrovascular polyp.

PMID- 12512024
TI  - The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel
      disease: a retrospective cohort study.
AB  - BACKGROUND & AIMS: 6-mercaptopurine/azathioprine is effective in IBD patients.
      However, data regarding toxicity associated with pregnancy are lacking, raising
      both patients' and physicians' concerns and sometimes resulting in elective
      abortion. METHODS: To evaluate potential toxicity of 6-mercaptopurine (6-MP), we
      reviewed the records of 485 patients who had received the drug. We contacted 462,
      of whom 155 had conceived at least 1 pregnancy after developing IBD. Pregnancies
      were analyzed as to whether the patient had taken 6-MP before, or at the time of,
      conception. These were compared with IBD patients who had their pregnancies
      before taking 6-MP. We collected data on live births, spontaneous abortions,
      prematurity, abortions secondary to birth defects, major and minor congenital
      birth defects, infections, and neoplasia. Outcomes were analyzed comparing
      pregnancies from men and women who had taken or were currently taking 6-MP to
      controls. RESULTS: There was no statistical difference in conception failures
      (defined as a spontaneous abortion), abortion secondary to a birth defect, major
      congenital malformations, neoplasia, or increased infections among male or female
      patients taking 6-MP compared with controls (RR = 0.85 [0.47-1.55], P = 0.59).
      CONCLUSIONS: 6-MP use before or at conception or during pregnancy appears to be
      safe. Discontinuation of the drug before and during pregnancy is not indicated.

PMID- 12512025
TI  - The prostaglandin E2 receptor-1 (EP-1) mediates acid-induced visceral pain
      hypersensitivity in humans.
AB  - BACKGROUND & AIMS: Central sensitization, an activity-dependent increase in
      spinal cord neuronal excitability, has been shown to contribute to esophageal
      pain hypersensitivity. Prostaglandin E2 (PGE(2)) is a mediator in both peripheral
      and central sensitization, in part via the prostaglandin E2 receptor-1 (EP-1),
      and may be a potential target for treating visceral pain. The purpose of this
      study was to determine whether acid-induced pain hypersensitivity within the non
      acid-exposed esophagus (secondary hyperalgesia) is mediated by PGE(2) activation
      of the EP-1 receptor. METHODS: Twelve healthy male subjects participated in a
      randomized, placebo-controlled crossover study. Upper esophageal pain thresholds
      (PTs) to electrical stimulation were determined, and either the EP-1 antagonist
      ZD6416 or a placebo was orally administered. One-hour after dosing, acid or
      saline (0.15 mol/L) was infused into the lower esophagus for 30 minutes. Upper
      esophageal PT was monitored for 120 minutes after infusion. RESULTS: Except in 1
      subject (who was excluded), the pH in the upper esophagus remained above 5
      throughout all studies. In 8 subjects, ZD6416 attenuated the reduction in PT in
      the upper esophagus normally induced by acid infusion into the lower esophagus
      (area under curve [AUC]: -11.9 +/- 2.5 and 6.4 +/- 6.7 for placebo and ZD6416,
      respectively; P < 0.01). After saline infusion, the effects of ZD6416 and placebo
      were similar (AUC: 9.9 +/- 6 and 4.1 +/- 2, respectively; P = 0.8). Three
      subjects had no reduction in PT to acid infusion with placebo and were excluded
      at post hoc analysis. CONCLUSIONS: The attenuation of secondary esophageal
      hyperalgesia by ZD6416 suggests that PGE(2), via the EP-1 receptor, contributes
      to human visceral pain hypersensitivity.

PMID- 12512026
TI  - Association between the C3435T MDR1 gene polymorphism and susceptibility for
      ulcerative colitis.
AB  - BACKGROUND & AIMS: The human multidrug resistance 1 (MDR1) gene product P
      glycoprotein is highly expressed in intestinal epithelial cells, where it
      constitutes a barrier against xenobiotics. The finding that mdr1a knockout mice
      develop a form of colitis that is similar to ulcerative colitis, which can be
      prevented by antibiotics, indicates a barrier function for P-glycoprotein against
      the invasion of bacteria or toxins. Because the MDR1 single nucleotide
      polymorphism C3435T is associated with lower intestinal P-glycoprotein
      expression, we tested whether this polymorphism predisposes to development of
      ulcerative colitis. METHODS: Allele frequencies and genotype distributions of the
      C3435T single nucleotide polymorphism were investigated in 149 patients with
      ulcerative colitis, 126 patients with Crohn's disease, and sex-matched healthy
      controls. RESULTS: Significantly increased frequencies of the 3435T allele and
      the 3435TT genotype were observed in patients with ulcerative colitis compared
      with controls (3435T: P = 0.049; odds ratio, 1.4; 95% confidence interval, 1.02
      1.94; 3435TT: P = 0.045; odds ratio, 2.03; 95% confidence interval, 1.04-3.95).
      In contrast, frequencies of the T allele and the TT genotype were the same in
      patients with Crohn's disease as in controls (P = 0.66 and P = 0.59,
      respectively). In comparison to 998 non-sex-matched controls, the effect for the
      TT genotype in ulcerative colitis patients was more pronounced (P = 0.0055; odds
      ratio, 2.1). CONCLUSIONS: The higher frequency of the 3435TT genotype in patients
      with ulcerative colitis corroborates the findings from the mdr1a knockout mice.
      The results support the notion that P-glycoprotein plays a major role in the
      defense against intestinal bacteria or toxins. Impairment of barrier function in
      3435TT subjects could render this genotype more susceptible to the development of
      ulcerative colitis.

PMID- 12512027
TI  - Intestinal glucose transport: evidence for a membrane traffic-based pathway in
      humans.
AB  - BACKGROUND & AIMS: The presence of glucose transporter 2 (GLUT2) molecules in the
      basolateral membrane of enterocytes has long been considered to be of major
      importance for intestinal glucose absorption. The aim of this study was to
      reevaluate the role of GLUT2 in a patient with congenital GLUT2 deficiency
      (Fanconi-Bickel syndrome, FBS). METHODS: Oral mono- and disaccharide tolerance
      tests including gaschromatographic determination of breath hydrogen
      concentrations were performed in an FBS patient. For comparison, a patient with a
      microsomal carbohydrate transport defect, glucose-6-phosphate translocase 1
      (G6PT1) deficiency, and a control individual were investigated. RESULTS: No
      increase in breath hydrogen concentration was found in the GLUT2-deficient
      patient after a glucose load. In G6PT1 deficiency, basal hydrogen concentrations
      were repeatedly found to be elevated. CONCLUSIONS: From the fact that a GLUT2
      deficient patient does not show any impairment of intestinal monosaccharide
      transport measurable by the hydrogen breath test, we conclude that mechanisms
      other than facilitative glucose transport by GLUT2 must be involved in the
      transport of monosaccharides at the basolateral membrane of enterocytes. When
      relating this observation to the high intestinal expression of human hexokinase,
      G6PT1, and glucose-6-phosphatase and to our results of oral carbohydrate
      tolerance tests in a G6PT1-deficient patient, there is evidence that a microsomal
      membrane traffic-based transport pathway, as recently suggested for GLUT2
      deficient animals, also plays a major role in transcellular monosaccharide
      transport of the human intestine.

PMID- 12512028
TI  - Appendectomy is followed by increased risk of Crohn's disease.
AB  - BACKGROUND & AIMS: Appendectomy is associated with a low risk of subsequent
      ulcerative colitis. This study analyzes the risk of Crohn's disease after
      appendectomy. METHODS: We followed-up 212,218 patients with appendectomy before
      age 50 years and a cohort of matched controls, identified from the Swedish
      Inpatient Register and the nationwide Census, for any subsequent diagnosis of
      Crohn's disease. RESULTS: An increased risk of Crohn's disease was found for more
      than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence
      interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18)
      after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric
      lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After
      nonperforated appendicitis, there was an increased risk among women but not among
      men (incidence rate ratio 1.37; 95% CI, 1.03-1.85, respectively, 0.89, 95% CI,
      0.64-1.24). Patients operated on before age 10 years had a low risk (incidence
      rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of
      perforated appendicitis had a worse prognosis. CONCLUSIONS: Appendectomy is
      associated with an increased risk of Crohn's disease that is dependent on the
      patient's sex, age, and the diagnosis at operation. The pattern of associations
      suggests a biologic cause.

PMID- 12512029
TI  - Protective association of aspirin/NSAIDs and esophageal cancer: a systematic
      review and meta-analysis.
AB  - BACKGROUND & AIMS: Esophageal carcinomas have high fatality rates, making
      chemoprevention agents desirable. We performed a systematic review with meta
      analysis of observational studies evaluating the association of
      aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and esophageal cancer.
      METHODS: We evaluated the MEDLINE, BIOSIS, and Web of Science electronic
      databases (1980-2001); manually reviewed the literature; and consulted with
      experts. Studies were included if they: (1) evaluated exposure to NSAIDs,
      aspirin, or both; (2) evaluated esophageal cancer; and (3) reported relative
      risks or odds ratios or provided data for their calculation. Data were
      independently abstracted by 2 investigators. The primary and sensitivity analyses
      used both fixed and random-effects models. RESULTS: Nine studies (2 cohort, 7
      case control) containing 1813 cancer cases were identified. All primary summary
      estimates were homogeneous. Statistical pooling showed a protective association
      between any use of aspirin/NSAID and esophageal cancer (odds ratio [OR] = 0.57;
      95% confidence interval [CI], 0.47-0.71). Both intermittent (OR = 0.82; CI, 0.67
      0.99) and frequent medication use were protective (OR = 0.54; CI, 0.43-0.67),
      with greater protection with more frequent use. Stratified by medication type,
      aspirin use was protective (OR = 0.5; CI, 0.38-0.66), and NSAIDs had a borderline
      protective association (OR = 0.75; CI, 0.54-1.0). Any use was protective against
      both esophageal adenocarcinoma (OR = 0.67; CI, 0.51-0.87) and squamous cell
      carcinoma (OR = 0.58; CI, 0.43-0.78). CONCLUSIONS: Pooled results support a
      protective association between aspirin and NSAIDs and esophageal cancer (of both
      histological types) and provide evidence for a dose effect. These findings
      support evaluating these agents in clinical trials of high-risk patients.

PMID- 12512030
TI  - Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival
      factors in colorectal adenocarcinomas.
AB  - BACKGROUND & AIMS: The effects of leukotriene (LT) D(4) on intestinal epithelial
      cells govern events that are involved in cell survival and colon cancer, notably
      increased expression of cyclooxygenase (COX)-2 and enhanced production of
      prostaglandin E(2). We investigated possible correlations between distribution of
      the recently described LTD(4) receptor CysLT(1)R and factors previously shown to
      be up-regulated by LTD(4) as well as clinicopathologic traits. METHODS:
      Immunohistochemistry and in situ hybridization were performed on tissue arrays,
      which were made using colorectal cancer samples from 84 patients. RESULTS:
      CysLT(1)R was significantly correlated to COX-2, 5-lipoxygenase, and Bcl-x(L).
      Male subjects more often exhibited high levels of this receptor relative to
      female subjects, and Dukes' B patients with elevated CysLT(1)R expression showed
      markedly poorer survival than those with low-level expression. Furthermore, this
      was paralleled by an increased viability of CysLT(1)R-overexpressing cells in a
      colon cancer cell line. CONCLUSIONS: Our results further implicate the
      involvement of LTs in colorectal carcinoma. Based on our present and earlier
      findings, we propose that LT/CysLT(1)R signaling facilitates survival of colon
      cancer cells, which may affect disease outcome. Like COX-2, LTs are accessible
      targets for pharmacologic treatment.

PMID- 12512031
TI  - Determinants of the association of overweight with elevated serum alanine
      aminotransferase activity in the United States.
AB  - BACKGROUND & AIMS: In the absence of other causes, overweight and obesity
      increase the risk of liver disease. We examined whether central adiposity and
      metabolic markers explain the association of body mass index (BMI as kg/m(2))
      with abnormal serum alanine aminotransferase (ALT) activity in a national,
      population-based study. METHODS: Adult participants (5724) in the third U.S.
      National Health and Nutrition Examination Survey (1988-1994) underwent
      anthropometric measures and phlebotomy after an overnight fast. Participants with
      excessive alcohol consumption, hepatitis B, hepatitis C, iron overload, or known
      diabetes were excluded. RESULTS: Elevated ALT levels were found in 2.8% of the
      population. In univariate analysis, factors associated with elevated ALT levels
      (P < 0.05) included younger age, male sex, Mexican-American ethnicity, and higher
      BMI, waist-to-hip circumference ratio (WHR), and fasting serum leptin,
      triglyceride, insulin, and glucose concentrations. The proportion of elevated ALT
      activity due to overweight and obesity (BMI > or =25 kg/m(2)) was 65%. In
      multivariate logistic regression analysis, control for WHR, demographic factors,
      and glucose concentration diminished but did not eliminate the association of
      higher BMI with elevated ALT activity. After adding leptin and insulin
      concentrations, abnormal ALT activity was most strongly associated with higher
      WHR (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.12-1.56) and leptin
      (OR, 1.12; 95% CI, 1.01-1.24) and insulin (OR, 1.27; 95% CI, 1.01-1.60)
      concentrations, whereas BMI was not independently related. CONCLUSIONS: In this
      large, national, population-based study, central adiposity, hyperleptinemia, and
      hyperinsulinemia were the major determinants of the association of overweight
      with elevated serum ALT activity.

PMID- 12512032
TI  - A prospective study characterizing full-length hepatitis B virus genomes during
      acute exacerbation.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) evolves rapidly in patients with
      chronic hepatitis B, and HBV variation may trigger acute exacerbation. To study
      this relationship, we investigated full-length viral sequences before, during,
      and after exacerbation. METHODS: We prospectively studied 14 patients with
      exacerbation of hepatitis B, either spontaneously (n = 4) or after receiving
      various medical interventions (n = 10), and measured their serum alanine
      aminotransferase (ALT) and HBV DNA levels monthly. Full-length HBV genomes at
      baseline, at the peak of serum viral load, at ALT peak, and after ALT peak were
      obtained by polymerase chain reaction, sequenced, and compared. Replication
      activities of serial HBV variants were assayed by in vitro transfection. RESULTS:
      Serum viral load was increased in all exacerbations. Viral peak preceded ALT peak
      in 13 (93%) of the 14 patients. At virologic peak, 12 patients (86%) harbored
      viral genome identical to the corresponding baseline genome. At and after ALT
      peak, 9 (64%) and 7 (50%) of the viral genomes remained identical to baseline,
      respectively. Mean nucleotide change per genome was 0.2 at virologic peak but
      increased to 4.4 and 8.1 at and after ALT peak, respectively. The replication
      potential of the viral variant that emerged during or after exacerbation was
      equivalent to that at baseline. CONCLUSIONS: Most exacerbations were preceded by
      an upsurge of serum HBV identical to the preexisting HBV strain. After
      exacerbation, about half of the patients were repopulated by a different viral
      variant, which was likely a result of immune selection.

PMID- 12512033
TI  - Model for end-stage liver disease (MELD) and allocation of donor livers.
AB  - BACKGROUND & AIMS: A consensus has been reached that liver donor allocation
      should be based primarily on liver disease severity and that waiting time should
      not be a major determining factor. Our aim was to assess the capability of the
      Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver
      recipients according to their severity of liver disease and mortality risk on the
      OPTN liver waiting list. METHODS: The MELD model predicts liver disease severity
      based on serum creatinine, serum total bilirubin, and INR and has been shown to
      be useful in predicting mortality in patients with compensated and decompensated
      cirrhosis. In this study, we prospectively applied the MELD score to estimate 3
      month mortality to 3437 adult liver transplant candidates with chronic liver
      disease who were added to the OPTN waiting list at 2A or 2B status between
      November, 1999, and December, 2001. RESULTS: In this study cohort with chronic
      liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list
      mortality increased directly in proportion to the listing MELD score. Patients
      having a MELD score <9 experienced a 1.9% mortality, whereas patients having a
      MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3
      month mortality as the end point, the area under the receiver operating
      characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the
      Child-Turcotte-Pugh (CTP) score (P < 0.001). CONCLUSIONS: These data suggest that
      the MELD score is able to accurately predict 3-month mortality among patients
      with chronic liver disease on the liver waiting list and can be applied for
      allocation of donor livers.

PMID- 12512034
TI  - Progression of fibrosis in chronic hepatitis C.
AB  - BACKGROUND & AIMS: Fibrosis is the hallmark of hepatic cirrhosis, worsening of
      which is probably the best surrogate marker for progression of chronic liver
      disease. We evaluated a large cohort of patients with chronic hepatitis C (CHC)
      using liver histology to assess the rate and predictors of progression of
      fibrosis. METHODS: The cohort consisted of 123 patients with CHC who underwent 2
      liver biopsies 4-212 months (mean, 44 months) apart without intervening
      treatment. Liver histology was graded using the histology activity index (score,
      0-18) and fibrosis staged using a scoring system of 0 (no fibrosis) to 6
      (cirrhosis). RESULTS: Among 123 patients, 48 (39%) showed progression in fibrosis
      scores, 46 (37%) showed no change, and 29 (24%) showed improvement. Of those with
      worsening fibrosis, 75% had a 1-point increase and 25% a 2-point or greater
      increase in scores, and 9% showed progression to cirrhosis. The overall rate of
      progression was 0.12 fibrosis units per year, a rate that predicts progression to
      cirrhosis in 50 years if progression was linear. The rate of fibrosis progression
      was variable, and it was higher among older patients, those with higher serum
      alanine and aspartate aminotransferase levels, and those with the most extensive
      periportal necrosis on initial liver biopsy. CONCLUSIONS: The best predictors of
      fibrosis progression in CHC are the extent of serum aminotransferase elevations
      and the degree of hepatocellular necrosis and inflammation on liver biopsy. These
      findings support the recommendation that patients with normal aminotransferase
      levels and mild liver histology can safely defer treatment.

PMID- 12512035
TI  - Histological outcome during long-term lamivudine therapy.
AB  - BACKGROUND & AIMS: One year of lamivudine for chronic hepatitis B results in
      histologic improvement. We aimed to assess the histological impact of longer-term
      treatment. METHODS: Sets of 3 liver biopsies, from 63 patients before and after 1
      year of randomized lamivudine treatment and after 2 years of further open-label
      treatment, were assigned Histologic Activity Index scores under code. RESULTS: At
      the end of year 1, 36/63 (57%) showed > or =2 point improvement and 24/63 (38%)
      no change in necroinflammatory activity; after 2 additional years of lamivudine,
      38/63 (60%) remained stable and 12/63 (19%) continued to improve. Worsening
      occurred in similar proportions of patients with and without YMDD (tyrosine,
      methionine, aspartate, aspartate) variants. After all 3 years of lamivudine
      treatment, 35/63 (56%) of patients showed improvement, 21/63 (33%) no change, and
      7/63 (11%) worsening. Those without, compared with those with, YMDD variants were
      more likely to improve (17/22 [77%] vs. 18/41 [44%]) and less likely to
      deteriorate (1/22 [5%] vs. 6/41 [15%]). Patients with YMDD variants for >2 years
      were least likely to improve (8/22 [36%]). Bridging fibrosis improved by > or =1
      level in 12/19 (63%), and cirrhosis improved (score of 4 to < or =3) in 8/11
      (73%). Only 1/52 [2%]) showed progression to cirrhosis, and 3/34 (9%) showed
      progression to bridging fibrosis (all with YMDD variants). CONCLUSIONS: Three
      years of lamivudine therapy reduces necroinflammatory activity and reverses
      fibrosis (including cirrhosis) in most patients. The emergence of YMDD variants
      blunts histologic responses; therefore, extended-duration YMDD variants may
      require additional therapies to maintain the histological benefit of treatment.

PMID- 12512036
TI  - Regulation of intestinal nuclear factor-kappaB activity and E-selectin expression
      during sepsis: a role for peroxynitrite.
AB  - BACKGROUND & AIMS: During sepsis, the production of both nitric oxide and
      superoxide are increased. Furthermore, NO and O(2)(-) may interact to produce
      peroxynitrite. The major aim of the present study was to assess the relative
      roles of NO, O(2)(-), and ONOO- in the regulation of nuclear factor kappaB (NF
      kappaB) activity and subsequent E-selectin expression during the early stages of
      sepsis. METHODS: Mice were administered 5 microg lipopolysaccharide (LPS)
      intraperitoneally, and NF-kappaB activity and E-selectin expression in the small
      intestine were assessed 3 hours later. RESULTS: In wild-type mice, increased
      levels of NF-kappaB in nuclear extracts were noted. By contrast, in both
      inducible nitric oxide synthase-deficient and transgenic Cu/Zn superoxide
      dismutase-overexpressing mice, NF-kappaB mobilization to the nucleus was
      diminished. Pretreatment with a ONOO- decomposition catalyst (5,10,15,20
      tetrakis[4-sulfonatophenyl]porphyrinato iron [III] [FeTPPS]) resulted in a
      diminished impact of LPS on NF-kappaB activation. LPS increased vascular E
      selectin expression in wild-type mice. E-selectin expression was diminished in
      inducible nitric oxide synthase-deficient mice after LPS challenge, but E
      selectin expression remained elevated in both Cu/Zn superoxide dismutase
      transgenic mice and wild-type mice pretreated with FeTPPS. CONCLUSIONS: Our
      observations suggest that NO, O(2)(-), and ONOO- production are all important
      mediators in the induction of NF-kappaB activity during endotoxemia and that, in
      vivo, E-selectin expression on endothelium may not always be associated with
      whole-organ NF-kappaB activation.

PMID- 12512037
TI  - Localization of orexin-1 receptors to vagal afferent neurons in the rat and
      humans.
AB  - BACKGROUND & AIMS: Orexin-A and -B are brain-gut peptides that stimulate food
      intake via orexin-R1 and -R2 receptors. Cholecystokinin (CCK) inhibits food
      intake via CCK(A) receptors expressed on vagal afferent neurons. The purpose of
      the study was to determine whether vagal afferent neurons express OX-R1 and OX-R2
      and whether orexin-A inhibits responses to CCK. METHODS: OX-R1 and -R2 expression
      by rat and human nodose ganglia was examined by reverse-transcriptase polymerase
      chain reaction (RT-PCR). Receptor localization was determined by
      immunohistochemistry. Responses of rat jejunal afferent fibers were examined by
      electrophysiology. RESULTS: Both rat and human nodose ganglia expressed OX-R1 as
      detected by RT-PCR, and humans also expressed OX-R2. The identity of the products
      was confirmed by sequencing. Immunohistochemistry indicated expression of OX-R1
      in both species in neurons that also expressed CCK(A) and leptin receptors. In
      human ganglia there was also expression in glial cells that was absent in rats.
      Orexin-A had no effect on the resting discharge of afferent nerve fibers but
      inhibited responses to CCK. CONCLUSIONS: OX-R1 and CCK(A) receptors are expressed
      by human and rat vagal afferent neurons. Orexin inhibits responses to CCK
      suggesting a role in modulation of gut to brain signaling.

PMID- 12512038
TI  - Crohn's disease-associated NOD2 variants share a signaling defect in response to
      lipopolysaccharide and peptidoglycan.
AB  - BACKGROUND & AIMS: The NOD2 variants R702W, G908R, and L1007fsinsC are strongly
      associated with Crohn's disease (CD) in both European and American populations,
      but whether this susceptibility extends to all ethnic groups remains unknown.
      Except for the L1007fsinsC mutation, which produces a truncated NOD2 protein, the
      functional activity of the major CD-associated variants G908R and R702W is
      unknown. METHODS: Individuals were genotyped for R702W, G908R, and L1007fsinsC.
      The ability of G908R, R702W, and L1007fsinsC variants in the presence and absence
      of P268S to confer responsiveness to lipopolysaccharide (LPS) and peptidoglycan
      (PGN) was determined in HEK293T kidney cells. RESULTS: G908R and L1007fsinsC, but
      not R702W, were associated with disease susceptibility in Ashkenazi Jews.
      Ashkenazi Jews with CD had significantly higher allele frequency carriage of
      G908R and lower carriage of R702W compared with non-Jewish whites with CD.
      Functional studies revealed that the G908R, R702W, and L1007fsinsC variants in
      the presence and absence of P268S are defective in their ability to respond to
      bacterial LPS and PGN, whereas P268S alone exhibited wild-type activity.
      CONCLUSIONS: R702W is not associated with susceptibility to CD in Ashkenazi Jews.
      The G908R, R702W, and L1007fsinsC variants share a common signaling defect in
      response to bacterial components, providing evidence for a unifying molecular
      mechanism whereby NOD2 mutations contribute to disease susceptibility.

PMID- 12512039
TI  - Liver fibrosis: insights into migration of hepatic stellate cells in response to
      extracellular matrix and growth factors.
AB  - BACKGROUND & AIMS: In liver fibrosis, alterations within the space of Disse
      microenvironment occur and facilitate further progression of chronic liver
      disease. The normal basement membrane-like matrix present within the space of
      Disse converts to a matrix rich in fibril-forming collagens during fibrosis.
      METHODS: To further understand the pathogenesis of liver fibrosis, we modified an
      in vitro Boyden chamber system to partially mimic in vivo conditions of hepatic
      stellate cells (HSCs) during health and disease. RESULTS: Stimulation of HSCs
      with platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)
      beta1, and/or epithelial growth factor (EGF) resulted in an increase in their
      migratory capacity and up-regulated matrix metalloproteinase (MMP)-2 activity.
      Migration induced by PDGF-BB was associated with increased proliferation, whereas
      TGF-beta1/EGF-induced migration was proliferation independent. COL-3, an
      inhibitor of MMP-2 and MMP-9, inhibited migration of HSCs induced by direct
      activation of PDGF-BB or TGF-beta1 but had no effect on migration induced by
      chemotactic stimuli without direct contact, suggesting 2 distinct MMP-dependent
      and MMP-independent mechanisms of PDGF-BB- or TGF-beta1-induced migration.
      Additionally, we show that type I collagen by itself induced migration of HSCs.
      Migration induced by PDGF-BB, TGF-beta1, and collagen I could be inhibited by
      alpha(1)- and/or alpha(2)-integrin blocking antibodies, collectively suggesting
      an integrin-dependent, MMP-2-mediated migration of HSCs. CONCLUSIONS: Basement
      membrane matrix integrity, composition, and cell-matrix interactions play an
      important role in anchoring HSCs and preventing them from spreading within the
      space of Disse and potentially elsewhere in the liver. Additionally, our data
      provide strong evidence for MMPs in regulation of HSCs migration.

PMID- 12512040
TI  - Induction of hepatic ABC transporter expression is part of the PPARalpha-mediated
      fasting response in the mouse.
AB  - BACKGROUND & AIMS: Fatty acids are natural ligands of the peroxisome proliferator
      activated receptor alpha (PPARalpha). Synthetic ligands of this nuclear receptor,
      i.e., fibrates, induce the hepatic expression of the multidrug resistance 2 gene
      (Mdr2), encoding the canalicular phospholipid translocator, and affect
      hepatobiliary lipid transport. We tested whether fasting-associated fatty acid
      release from adipose tissues alters hepatic transporter expression and bile
      formation in a PPARalpha-dependent manner. METHODS: A 24-hour fasting/48-hour
      refeeding schedule was used in wild-type and Pparalpha((-/-)) mice. Expression of
      genes involved in the control of bile formation was determined and related to
      secretion rates of biliary components. RESULTS: Expression of Pparalpha,
      farnesoid X receptor, and liver X receptor alpha genes encoding nuclear receptors
      that control hepatic bile salt and sterol metabolism was induced on fasting in
      wild-type mice only. The expression of Mdr2 was 5-fold increased in fasted wild
      type mice and increased only marginally in Pparalpha((-/-)) mice, and it
      normalized on refeeding. Mdr2 protein levels and maximal biliary phospholipid
      secretion rates were clearly increased in fasted wild-type mice. Hepatic
      expression of the liver X receptor target genes ATP binding cassette transporter
      a1 (Abca1), Abcg5, and Abcg8, implicated in hepatobiliary cholesterol transport,
      was induced in fasted wild-type mice only. However, the maximal biliary
      cholesterol secretion rate was reduced by approximately 50%. CONCLUSIONS:
      Induction of Mdr2 expression and function is part of the PPARalpha-mediated
      fasting response in mice. Fasting also induces expression of the putative
      hepatobiliary cholesterol transport genes Abca1, Abcg5, and Abcg8, but,
      nonetheless, maximal biliary cholesterol excretion is decreased after fasting.

PMID- 12512041
TI  - New method of delivering gene-altered Kupffer cells to rat liver: studies in an
      ischemia-reperfusion model.
AB  - BACKGROUND & AIMS: Kupffer cells play a major role in the pathogenesis of several
      diseases. They release physiologically active substances that often lead to
      localized tissue injury. Therefore, the aim of this study was to establish a
      model to protect the liver through supplementation of Kupffer cells that have
      been transduced by recombinant adenovirus. METHODS: Optimal conditions for
      intravenous injection in rats were established using carbon-labeled Kupffer
      cells. Adenoviral-transduced Kupffer cells encoding the Cu/Zn-SOD gene (Ad.SOD1)
      or beta-galactosidase reporter gene (Ad.LacZ) were transplanted into recipient
      rats. Twenty-four hours after transplantation, 70% hepatic ischemia-reperfusion
      was used to induce hepatic oxidative stress, and liver injury was determined 8 or
      24 hours later. RESULTS: In initial experiments, 10%-20% of the injected carbon
      labeled cells were localized in the host liver after 24 hours, representing
      approximately 1% of the total population of Kupffer cells. Pretreatment of the
      recipient with a single dose of cyclosporin A maximized Kupffer cell reseeding up
      to 4%-10% of the total Kupffer cell population, suggesting that efficiency is
      limited by host immune response. Moreover, reseeded Kupffer cells were retained
      in host livers for up to 14 days after transplant. In livers of animals injected
      with Kupffer cells transduced with Ad.LacZ, transgene expression was observed,
      indicating Kupffer cell functional integrity. Injection of Kupffer cells
      transduced with Ad.SOD1 significantly blunted the increase in serum transaminases
      and liver injury because of ischemia-reperfusion compared with controls.
      CONCLUSIONS: This novel approach allows delivery of transduced Kupffer cells in
      rats, which can be used as an investigative tool as well as a therapeutic
      strategy against inflammatory liver diseases.

PMID- 12512042
TI  - Peroxisome proliferator-activated receptor-beta signaling contributes to enhanced
      proliferation of hepatic stellate cells.
AB  - BACKGROUND & AIMS: The peroxisome proliferator-activated nuclear receptors (PPAR
      alpha, PPAR-beta, and PPAR-gamma), which modulate the expression of genes
      involved in energy homeostasis, cell cycle, and immune function, may play a role
      in hepatic stellate cell activation. Previous studies focused on the decreased
      expression of PPAR-gamma in hepatic stellate cell activation but did not
      investigate the expression and role of the PPAR-alpha and -beta isotypes. The aim
      of this study was to evaluate the expression of the different PPARs during
      hepatic stellate cell activation in vitro and in situ and to analyze possible
      factors that might contribute to their expression. In a second part of the study,
      the effect of a PPAR-beta agonist on acute liver injury was evaluated. METHODS:
      The effects of PPAR isotype-specific ligands on hepatic stellate cell transition
      were evaluated by bromodeoxyuridine incorporation, gel shifts,
      immunoprecipitation, and use of antisense PPAR-beta RNA-expressing adenoviruses.
      Tumor necrosis factor alpha-induced PPAR-beta phosphorylation and expression was
      evaluated by metabolic labeling and by using specific P38 inhibitors. RESULTS:
      Hepatic stellate cells constitutively express high levels of PPAR-beta, which
      become further induced during culture activation and in vivo fibrogenesis. No
      significant expression of PPAR-alpha or -gamma was found. Stimulation of the P38
      mitogen-activated protein kinase pathway modulated the expression of PPAR-beta.
      Transcriptional activation of PPAR-beta by L165041 enhanced hepatic stellate cell
      proliferation. Treatment of rats with a single bolus of CCl(4) in combination
      with L165041 further enhanced the expression of fibrotic markers. CONCLUSIONS:
      PPAR-beta is an important signal-transducing factor contributing to hepatic
      stellate cell proliferation during acute and chronic liver inflammation.

PMID- 12512043
TI  - Beta-catenin antisense studies in embryonic liver cultures: role in
      proliferation, apoptosis, and lineage specification.
AB  - BACKGROUND & AIMS: Wnt/beta-catenin pathway activation occurs during liver growth
      in hepatoblastomas, hepatocellular cancers, and liver regeneration. The aim of
      this study was to investigate the role of beta-catenin, a key component of the
      Wnt pathway, in liver development as well as its normal distribution in
      developing liver. METHODS: Embryonic liver cultures and beta-catenin antisense
      phosphorodiamidate morpholino oligomer (PMO) were used to elucidate the role of
      beta-catenin in liver development. Livers from embryos at 10 days of gestational
      development were cultured in the presence of antisense or control PMO for 72
      hours and analyzed. RESULTS: Beta-catenin shows stage-specific localization and
      distinct distribution compared with known markers in developing liver. A
      substantial decrease in beta-catenin protein was evident in the organs cultured
      in the presence of antisense. Beta-catenin inhibition decreased cell
      proliferation and increased apoptosis in these organ cultures. Presence of
      antisense resulted in loss of CK19 immunoreactivity of the bipotential stem
      cells. Beta-catenin inhibition also promoted c-kit immunoreactivity of the
      hepatocytes. CONCLUSIONS: We conclude that the PMO antisense to beta-catenin
      effectively inhibits synthesis of its protein. Beta-catenin modulates cell
      proliferation and apoptosis in developing liver. It may play a significant role
      in early biliary lineage commitment of the bipotential stem cells and also seems
      to be important in hepatocyte maturation.

PMID- 12512044
TI  - Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene
      mutation and effect of bile acid therapy.
AB  - BACKGROUND & AIMS: Inborn errors of bile acid metabolism may present as neonatal
      cholestasis and fat-soluble vitamin malabsorption or as late onset chronic liver
      disease. Our aim was to fully characterize a defect in bile acid synthesis in a 2
      week-old African-American girl presenting with coagulopathy, vitamin D and E
      deficiencies, and mild cholestasis and in her sibling, whose liver had been used
      for orthotopic liver transplantation (OLT). METHODS: Bile acids were measured by
      mass spectrometry in urine, bile, serum, and feces of the patient and in urine
      from the unrelated recipient. RESULTS: Liver biopsy specimens showed neonatal
      hepatitis with giant cell transformation and hepatocyte necrosis; peroxisomes
      were reduced in number. High concentrations of (25R)3alpha,7alpha,12alpha
      trihydroxy-5beta-cholestanoic acid in the urine, bile, and serum established a
      pattern similar to that of Zellweger syndrome and identical to the Alligator
      mississippiensis. Serum phytanic acid was normal, whereas pristanic acid was
      markedly elevated. Biochemical, MRI, and neurologic findings were inconsistent
      with a generalized defect of peroxisomal function and were unique. Analysis of
      the urine from the recipient of the deceased sibling's liver confirmed the same
      bile acid synthetic defect. A deficiency in 2-methylacyl-CoA racemase, which is
      essential for conversion of (25R)THCA to its 25S-isomer, the substrate to
      initiate peroxisomal beta-oxidation to primary bile acids, was confirmed by DNA
      analysis revealing a missense mutation (S52P) in the gene encoding this enzyme.
      Long-term treatment with cholic acid normalized liver enzymes and prevented
      progression of symptoms. CONCLUSIONS: This genetic defect further highlights bile
      acid synthetic defects as a cause of neonatal cholestasis.

PMID- 12512045
TI  - American Gastroenterological Association medical position statement: Diagnosis
      and care of patients with anal fissure.

PMID- 12512046
TI  - AGA technical review on the diagnosis and care of patients with anal fissure.

PMID- 12512047
TI  - NSAIDs and esophageal cancer: ready for trials but not yet broad clinical
      application.

PMID- 12512048
TI  - Defining nonalcoholic fatty liver disease: implications for epidemiologic
      studies.

PMID- 12512049
TI  - MELD: the answer or just more questions?

PMID- 12512050
TI  - Biliary lipid secretion, membrane pumps, and the metabolic response to fasting:
      distinct PPAR-ts of a common regulatory pathway.

PMID- 12512051
TI  - Virtual colonography--a step forward?

PMID- 12512052
TI  - Insights into milk protein allergy: microenvironment matters.

PMID- 12512054
TI  - Understanding the course.

PMID- 12512056
TI  - Transcription factors and cholangiocyte development.

PMID- 12512060
TI  - JC virus and human colon carcinoma: an intriguing and inconclusive association.

PMID- 12512062
TI  - WNT-inducible signaling pathway protein 3, WISP-3, is mutated in microsatellite
      unstable gastrointestinal carcinomas but not in endometrial carcinomas.

PMID- 12512063
TI  - Bile acids and esophageal cancer.

PMID- 12512064
TI  - NOD2 insertion mutation in a Cretan Crohn's disease population.

PMID- 12512066
TI  - The "innocent colon" and K-ras mutation--guilty by (ACF) association?

PMID- 12512072
TI  - Exploring protein-protein interactions with phage display.
AB  - Protein-protein interactions mediate essentially all biological processes. A
      detailed understanding of these interactions is thus a major goal of modern
      biological chemistry. In recent years, genome sequencing efforts have revealed
      tens of thousands of novel genes, but the benefits of genome sequences will only
      be realized if these data can be translated to the level of protein function.
      While genome databases offer tremendous opportunities to expand our knowledge of
      protein-protein interactions, they also present formidable challenges to
      traditional protein chemistry methods. Indeed, it has become apparent that
      efficient analysis of proteins on a proteome-wide scale will require the use of
      rapid combinatorial approaches. In this regard, phage display is an established
      combinatorial technology that is likely to play an even greater role in the
      future of biology. This article reviews recent applications of phage display to
      the analysis of protein-protein interactions. With combinatorial mutagenesis
      strategies, it is now possible to rapidly map the binding energetics at protein
      protein interfaces through statistical analysis of phage-displayed protein
      libraries. In addition, naive phage-displayed peptide libraries can be used to
      obtain small peptide ligands to essentially any protein of interest, and in many
      cases, these binding peptides act as antagonists or even agonists of natural
      protein functions. These methods are accelerating the pace of research by
      enabling the study of complex protein-protein interactions with simple molecular
      biology methods. With further optimization and automation, it may soon be
      possible to study hundreds of different proteins in parallel with efforts
      comparable to those currently expended on the analysis of individual proteins.

PMID- 12512073
TI  - Total enantioselective synthesis and in vivo biological evaluation of a novel
      fluorescent BODIPY alpha-galactosylceramide.
AB  - Natural killer T (NKT) cells are a distinct subset of mature lymphocytes endowed
      with features of activated and regulatory T cells. alpha-Galactosylceramides
      (alpha-GalCers), the synthetic prototype of which is KRN7000, are the only
      natural reagents recognised by the T-cell receptor of NKT cells. The alpha-GalCer
      activated NKT cells promptly release IFN gamma and IL-4 (IFN=interferon;
      IL=interleukin) and undergo apoptotic death within hours. In mice, activated NKT
      cells are responsible for antitumour activity and protection against autoimmune
      diseases. KRN7000 can thus be considered as the root of a family of novel
      immunoregulatory drugs. To get insights into the in vivo behaviour of alpha
      galactosylceramides, an original fluorescent derivative has been prepared by
      following a convergent synthetic scheme. This strategy allows the introduction of
      different acyl chains, carbohydrate residues and various labels in the final
      steps of the synthesis. The fluorescent BODIPY probe derived from a versatile
      glycolipid precursor is as active as KRN7000 for inducing apoptosis of liver NKT
      cells. Fluorescence was detected in peritoneal macrophages and splenic antigen
      presenting cells, in Kupffer-like cells in the liver, but not in lymphocytes.

PMID- 12512074
TI  - Assembly of designed oligonucleotides as an efficient method for gene
      recombination: a new tool in directed evolution.
AB  - A new and practical method for gene recombination with formation of libraries of
      mutant genes is presented. The method is based on the assembly of appropriately
      prepared oligonucleotides whose design is guided by sequence information. High
      recombination frequency with formation of full-length products is achieved by
      controlled overlapping of the designed oligomers. This process (ADO) minimizes
      self-hybridization of parental genes, which constitutes a significant advantage
      over conventional family shuffling as used in the directed evolution of
      functional enzymes. ADO was applied to the recombination of two lipase family
      genes from Bacillus subtilis (LipA and LipB). In a library of 3000 lipase
      variants created by this method, several were found that display increased
      enantioselectivity in a model reaction involving the hydrolysis of a meso
      diacetate.

PMID- 12512075
TI  - Solution structure and stability of tryptophan-containing nucleopeptide duplexes.
AB  - Covalently linked peptide-oligonucleotide hybrids were used as models for
      studying tryptophan-DNA interactions. The structure and stability of several
      hybrids in which peptides and oligonucleotides are linked through a
      phosphodiester bond between the hydroxy group of a homoserine (Hse) side chain
      and the 3'-end of the oligonucleotide, have been studied by both NMR and CD
      spectroscopy and by restrained molecular dynamics methods. The three-dimensional
      solution structure of the complex between Ac-Lys-Trp-Lys-Hse(p3'dGCATCG)-Ala-OH
      (p=phosphate, Ac=acetyl) and its complementary strand 5'dCGTAGC has been
      determined from a set of 276 experimental NOE distances and 33 dihedral angle
      constraints. The oligonucleotide structure is a well-defined duplex that belongs
      to the B-form family of DNA structures. The covalently linked peptide adopts a
      folded structure in which the tryptophan side chain stacks against the 3'
      terminal guanine moiety, which forms a cap at the end of the duplex. This
      stacking interaction, which resembles other tryptophan-nucleobase interactions
      observed in some protein-DNA complexes, is not observed in the single-stranded
      form of Ac-Lys-Trp-Lys-Hse(p3'dGCATCG)-Ala-OH, where the peptide chain is
      completely disordered. A comparison with the pure DNA duplex, d(5'GCTACG3')
      (5'CGTAGC3'), indicates that the interaction between the peptide and the DNA
      contributes to the stability of the nucleopeptide duplex. The different
      contributions that stabilize this complex have been evaluated by studying other
      nucleopeptide compounds with related sequences.

PMID- 12512076
TI  - Design of a composite ethidium-netropsin-anilinoacridine molecule for DNA
      recognition.
AB  - Control of gene expression is a cherished goal of cancer chemotherapy. Small
      ligand molecules able to bind tightly to DNA in a well-defined configuration are
      being actively searched for. With this goal in mind, we have designed and
      synthesized the trifunctional molecule R-132, which combines a bispyrrole
      skeleton for minor groove DNA recognition and two different chromophores,
      anilinoacridine and ethidium. The affinity and mode of binding of R-132 to DNA
      were studied by a combination of complementary biochemical and biophysical
      techniques, which included absorption and fluorescence spectroscopy and circular
      and linear dichroism. A surface plasmon resonance biosensor analysis was also
      performed to quantify the kinetic parameters of the drug-DNA interaction process.
      Altogether, the results demonstrate that the three moieties of the hybrid
      molecule are engaged in the interaction process, thus validating the rational
      design strategy. At the biological level, R-132 stabilizes topoisomerase-II-DNA
      covalent complexes and displays potent cytotoxic activities, which are
      attributable to its DNA-binding properties. R-132 easily enters and accumulates
      in cell nuclei, as evidenced by confocal microscopy. R-132 therefore provides a
      novel lead compound for the design of gene-targeted anticancer agents.

PMID- 12512077
TI  - Synthesis and biological activity of a platinum(II) 6-phenyl-2,2'-bipyridine
      complex and its dimeric analogue.
AB  - We have synthesized (pyridyl)-(6-phenyl-2,2'-bipyridine)platinum(II)
      hexafluorophosphate (1) and its corresponding dimer, micro-N,N'-bis(isonicotinyl)
      1,6-hexanediamino bis-[6-phenyl-2,2'-bipyridine-platinum(II)] dichloride (2). The
      DNA binding constants of 1 and 2 at 20 degrees C were determined by absorption
      titration to be 2.25 x 10(4) M(-1) and 3.07 x 10(6) M(-1), respectively. Compound
      1 showed an AT preference, while 2 had no base preference. The binding site sizes
      of 2 for [poly(dA-dT)](2), calf thymus DNA (ctDNA), and [poly(dG-dC)](2), as
      determined by fluorescence titration, were 6.6, 4.0, and 2.8 bp, respectively.
      Compound 2 probably bound to [poly(dA-dT)](2) through bisintercalation, and to
      [poly(dG-dC)](2) by monointercalation. Binding of DNA by both complexes is
      favorable, since the binding free energies of 1 and 2 were estimated to be -5.8
      and -8.7 kcal mol(-1), respectively. The results of viscosity measurements and
      gel mobility shift assay demonstrated that binding of 1 and 2 caused DNA
      lengthening. The cytotoxicities of the complexes in various human cancer cell
      lines were determined by MTT assay. Complex 2 exhibited cytotoxicity comparable
      to that of cisplatin, and was more toxic than 1 by an order of magnitude.

PMID- 12512078
TI  - Synthesis and biological evaluation of pyrazolylnaphthoquinones as new potential
      antiprotozoal and cytotoxic agents.
AB  - The importance of American trypanosomiasis (Chagas' disease) in human pathology
      is widely known. The prognosis of this disease is poor and the choice of
      effective medicines limited, thus study of new drugs is absolutely necessary. In
      this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic
      naphthoquinones bearing 3-aminopyrazole rings, were evaluated on Trypanosoma
      cruzi, the etiological agent of Chagas' disease. These activities were compared
      with those of three 5-aminoisoxazole analogues. In addition, since these
      compounds belong to a family of antiprotozoal and cytotoxic/antitumor agents, the
      activities of all six against Plasmodium falciparum, Trypanosoma brucei
      rhodesiense, and murine L-6 cells were also investigated. In the biological
      tests, five of the compounds showed significant in vitro trypanocidal activities
      against T. cruzi, with activities similar to that of benznidazole. Two of the 5
      aminoisoxazole analogues also showed good activities, in one case highly
      selective, against the K1 and NF54 strains of P. falciparum (IC(50)<0.12 microg
      mL(-1)). Three of the compounds were cytotoxic to murine L-6 cells (IC(50)=0.21
      0.50 microg mL(-1)). The results suggested that the three
      pyrazolylnaphthoquinones and one of the 5-aminoisoxazole analogues could be
      starting points for lead optimization programs against T. cruzi and P.
      falciparum, respectively.

PMID- 12512079
TI  - Conformational features of human melanin-concentrating hormone: an NMR and
      computational analysis.
AB  - The conformational features of human melanin-concentrating hormone (hMCH) [Asp1
      Phe2-Asp3-Met4-Leu5-Arg6-cyclo(S[bond]S)(Cys7-Met8-Leu9-Gly10-Arg11-Val12-Tyr13
      Arg14-Pro15-Cys16)-Trp17-Gln18-Val19], in water and in a CD(3)CN/H(2)O (1:1 v/v)
      mixture at 298 K, have been determined by NMR spectroscopy followed by simulated
      annealing and molecular dynamics analyses to identify conformer populations.
      Backbone clustering analysis of NMR-spectroscopy-derived structures in the 7-16
      peptide region led to the identification of a single representative structure in
      each solvent. Both root mean square deviation clustering and secondary structure
      analysis of the final conformers in both solvents show substantial convergence of
      most conformers into a single fold in the 4-17 region, with a limited variability
      around Gly10 and Tyr13 on going from CD(3)CN/H(2)O to pure water. The main
      feature deduced from the analysis of secondary structures is the occurrence of an
      N-terminal alpha helix of variable length, which spans an overall residue range
      of 2-9. A comparative analysis in the two solvents highlights that these
      structures are substantially different from that reported in the literature for
      the cyclic MCH(5-14) subunit of salmon MCH, which was used to perform a molecular
      characterization of the MCH/receptor complex. Our conformational data call for a
      critical revision of the proposed MCH/receptor complex model.

PMID- 12512080
TI  - Optimization of electrochemical and peroxide-driven oxidation of styrene with
      ultrathin polyion films containing cytochrome P450cam and myoglobin.
AB  - The catalytic and electrochemical properties of myoglobin and cytochrome
      P450(cam) in films constructed with alternate polyion layers were optimized with
      respect to film thickness, polyion type, and pH. Electrochemical and hydrogen
      peroxide driven epoxidation of styrene catalyzed by the proteins was used as the
      test reaction. Ionic synthetic organic polymers such as poly(styrene sulfonate),
      as opposed to SiO(2) nanoparticles or DNA, supported the best catalytic and
      electrochemical performance. Charge transport involving the iron heme proteins
      was achieved over 40-320 nm depending on the polyion material and is likely to
      involve electron hopping facilitated by extensive interlayer mixing. However,
      very thin films (ca. 12-25 nm) gave the largest turnover rates for the catalytic
      epoxidation of styrene, and thicker films were subject to reactant transport
      limitations. Classical bell-shaped activity/pH profiles and turnover rates
      similar to those obtained in solution suggest that films grown layer-by-layer are
      applicable to turnover rate studies of enzymes for organic oxidations. Major
      advantages include enhanced enzyme stability and the tiny amount of protein
      required.

PMID- 12512081
TI  - Novel trifluoromethyl ketones as potent gastric lipase inhibitors.
AB  - Novel inhibitors of human digestive lipases, lipophilic trifluoromethyl ketones,
      were developed. These analogues of the natural triacylglycerol substrates of
      lipases were designed to contain the carbonyl group of the trifluoromethyl ketone
      functionality in place of the carbonyl group of the scissile ester bond at the sn
      1 position. The ester bond at the sn-3 position was replaced by an ether bond,
      while the secondary hydroxy group was either esterified or etherified. The
      inhibitors were prepared starting from solketal. The inhibition of human
      pancreatic and gastric lipases by the trifluoromethyl ketones was studied by the
      monolayer technique. 5,5,5-Trifluoro-1-(dodecyloxymethyl)-4-oxopentyl decanoate
      is the best synthetic inhibitor of human gastric lipase ever reported (inhibition
      constant alpha(50)=0.003).

PMID- 12512082
TI  - Evaluation of lipopolysaccharide aggregation by light scattering spectroscopy.
AB  - Lipopolysaccharides (LPS) are cell wall components of Gram-negative bacteria.
      These molecules behave as bacterial endotoxins and their release into the
      bloodstream is a determinant of the development of a wide range of pathologies.
      These amphipathic molecules can self-aggregate into supramolecular structures
      with different shapes and sizes. The formation of these structures occurs when
      the LPS concentration is higher than the apparent critical micelle concentration
      (CMC(a)). Light scattering spectroscopy (both static and dynamic) was used to
      directly characterize the aggregation process of LPS from Escherichia coli
      serotype 026:B6. The results point to a CMC(a) value of 14 microg mL(-1) and the
      existence of premicelle LPS oligomers below this concentration. Both structures
      were characterized in terms of molecular weight (5.5 x 10(6) and 16 x 10(6) g
      mol(-1) below and above the CMC(a), respectively), interaction with the aqueous
      environment, gyration radius (56 and 105 nm), hydrodynamic radius, (60 and 95 nm)
      and geometry of the supramolecular structures (nearly spherical). Our data
      indicates that future in vitro experiments should be carried out both below and
      above the CMC(a). The search for drugs that interact with the aggregates, and
      thus change the CMC(a) and condition LPS interactions in the bloodstream, could
      be a new way to prevent certain bacterial-endotoxin-related pathologies.

PMID- 12512083
TI  - Analysis of protein tyrosine kinase inhibitors in recombinant yeast lacking the
      ERG6 gene.
AB  - Studies of small-molecule-protein interactions in yeast can be hindered by the
      limited permeability of yeast to small molecules. This diminished permeability is
      thought to be related to the unique sterol composition of fungal membranes, which
      are enriched in the steroid ergosterol. We report the construction of the novel
      Saccharomyces cerevisiae yeast strain DCY250, which is compatible with yeast two
      hybrid-based systems and bears a targeted disruption of the ERG6 gene to ablate
      ergosterol biosynthesis and enhance permeability to small molecules. The small
      molecule inhibitors of protein tyrosine kinases (PTKs) PP1, PP2, herbimycin A,
      and staurosporine were investigated with yeast tribrid systems that detect the
      activity of the PTKs v-Abl and v-Src. These tribrid systems function by
      expression of the PTK, a B42 activation domain fused to the phosphotyrosine
      binding Grb2 SH2 domain, a DNA-bound LexA-GFP-(AAYANAA)(4) universal PTK
      substrate, and a lacZ reporter gene. Yeast genetic systems that lack functional
      ERG6 were found to be as much as 20-fold more sensitive to small-molecule
      inhibitors of PTKs than systems with ERG6, and these deficient systems may
      provide a useful platform for the discovery and analysis of small-molecule
      protein interactions.

PMID- 12512084
TI  - Urdamycin L: a novel metabolic shunt product that provides evidence for the role
      of the urdM gene in the urdamycin A biosynthetic pathway of Streptomyces fradiae
      TU 2717.

PMID- 12512085
TI  - Site-specific cleavage of the HIV-1 TAR RNA by a hydroxysalen-copper(III)
      complex.

PMID- 12512086
TI  - The biosynthesis of indolocarbazoles in a heterologous E. coli host.

PMID- 12512088
TI  - Is the atmospheric pressure chemical ionisation and collisionally induced
      methanol loss from protonated dehydroamino acids a retrosynthetic process?
AB  - Unsaturated 5(4H)-oxazolones lead, by methanolysis, to the corresponding
      dehydroamino acid derivatives. Interestingly, under atmospheric pressure chemical
      ionisation (APCI) conditions, the latter give rise, aside from abundant [M+H](+)
      ions, to [MHbondCH(3)OH](+) species, formally corresponding to the protonated
      oxazolones employed for their synthesis. Retrosynthetic processes have often been
      described as energetically favoured decompositions of odd-electron molecular ions
      but never invoked in APCI-activated fragmentations. To investigate this possible
      retrosynthetic process, occurring also under collisional conditions, some
      experiments on the deuterated analogues have been undertaken. The breakdown
      curves of [M+H](+) of oxazolones and [MHbondCH(3)OH](+) of the dehydroamino acid
      derivatives are superimposable, proving their structural identity and giving
      experimental evidence of the occurrence of a real retrosynthetic process from
      even-electron protonated molecules.

PMID- 12512089
TI  - Metal ion complexes in the structural analysis of phospholipids by electrospray
      ionization tandem mass spectrometry.
AB  - The effects of metal cationization on collisionally activated dissociation (CAD)
      of phospholipids were investigated by electrospray ionization with quadrupole ion
      trap tandem mass spectrometry. The metal ions include Li(+), Na(+), K(+), Sr(2+),
      Ba(2+), and the first transition series. CAD of the transition metal ion-bound
      lipid complexes gave significant yields of product ions that identify the
      positions of the two fatty acyl substituents on the glycerophospholipid backbone.
      The cobalt(II) ion, which has a single naturally occurring isotope, was expected
      to be a better cationization reagent as it produces simpler mass spectra than
      other transition metal ions. CAD of the cobalt(II) ion complexes of
      glycerophosphoethanolamines, glycerophosphoglycerols and glycerophosphoserines
      yielded product ions that revealed information regarding both the lipid classes
      and the regiospecific positions of the two fatty acyl substituents.

PMID- 12512090
TI  - Study of the attachment of Na+ on glucose and on some of its methylated
      derivatives.
AB  - The mechanism of attachment of Na(+) on glucose, methyl-alpha-D-glucose, methyl
      beta-D-glucose, 3-O-methylglucose, tetra-O-methylglucose, and also on galactose
      and methyl-beta-D-galactose, was studied. For this we measured the ion yields for
      the complex [sugar-Na(+)] formed by ionisation by matrix-assisted laser
      desorption/ionisation (MALDI) and ionspray. These data were compared with the
      relative volatilities and hydrophobicities of the sugars, measured by evaporative
      light scattering and reversed-phase liquid chromatography, respectively. Some
      formation enthalpies for the complexes [sugar-Na(+)], starting from the sugar and
      the cation, were obtained by ab initio calculations. No simple correlations could
      be observed between the ion yields and the parameters studied, so that the
      cationisation mechanism of the sugars remains unclear.

PMID- 12512091
TI  - An improved liquid chromatography/tandem mass spectrometry method for the
      determination of 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA samples using
      immunoaffinity column purification.
AB  - The analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents an
      important biomarker of oxidative stress. A sensitive method for the detection of
      8-oxodG in DNA samples has been developed that utilizes immunoaffinity column
      purification of 8-oxodG followed by liquid chromatography/mass spectrometry/mass
      spectrometry (LC/MS/MS) multiple reaction monitoring (MRM) mode analysis. An
      internal standard of stable-isotopically labelled 8-oxodG containing [(15)N(5)]
      was added prior to the enzymatic digestion of DNA to deoxynucleosides, which was
      then subjected to immunoaffinity column purification followed by microbore
      positive ion LC/MS/MS MRM. The 8-oxo-7,8-dihydroguanine (8-oxoG) base product ion
      at m/z 168 was monitored following cleavage of the glycosidic bond of the 8-oxodG
      [M+H](+) ion at m/z 284. Similar determinations were made for [(15)N(5)]8-oxodG
      by monitoring the [(15)N(5)]8-oxoG base product ion at m/z 173 formed from the
      [M+H](+) ion at m/z 289. The introduction of the immunoaffinity column
      purification step into the method represents a significant improvement for the
      accurate determination of 8-oxodG since all artefactual peaks that are observed
      following the direct injection of digested DNA onto the LC/MS/MS system are
      removed. The identity of these artefactual peaks has been confirmed to be 2'
      deoxyguanosine (dG), thymidine (dT) and 2'-deoxyadenosine (dA). The presence of
      these artefactual peaks in MRM mode analysis can be explained as a consequence of
      a concentration effect due to their considerably higher relative abundance in DNA
      compared to 8-oxodG. The highest signal intensity was observed for the
      artefactual peak for dA due to the fact that the adenine base formed an adduct
      with methanol, which is a constituent of the mobile phase. The resulting [M+H](+)
      ion at m/z 284 (dA m/z 252 + CH(3)OH m/z 32) gave rise to a product ion at m/z
      168 following the loss of deoxyribose in MRM mode analysis. Control calf thymus
      DNA was digested to deoxynucleosides and unmodfied deoxynucleosides were removed
      by immunoaffinity column purification; the enriched 8-oxodG was determined by
      LC/MS/MS MRM. The level of 8-oxodG in control calf thymus DNA was determined to
      be 28.8 +/- 1.2 8-oxodG per 10(6) unmodified nucleotides (n = 5) using 5 microg
      of digested DNA. The limit of detection of the microbore LC/MS/MS MRM for 8-oxodG
      was determined to be 25 fmol on-column with a signal-to-noise ratio of 3.5.

PMID- 12512092
TI  - Quantitative analysis of clindamycin in human plasma by liquid
      chromatography/electrospray ionisation tandem mass spectrometry using d1-N
      ethylclindamycin as internal standard.
AB  - A new method for the quantitative analysis of clindamycin in human plasma by
      liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI
      MS/MS) is presented. Recently published methods possess a disadvantage because of
      their use of internal standards with extraction and ionisation properties
      different from those of clindamycin. To avoid these problems, d(1)-N
      ethylclindamycin was synthesised for use as internal standard by N-demethylation
      and subsequent d(1)-N-ethylation. Plasma sample preparation was done by an easy
      and rapid liquid-liquid extraction using ethyl acetate. The method was validated
      in the expected concentration range for a pharmacokinetic study. Calibration
      graphs were linear within the range 0.05-3.2 microg/mL plasma. Intra-day
      precision was between 0.90% (2.8 microg/mL) and 3.25% (0.05 microg/mL), inter-day
      variability was found to be between 1.33% (0.7 microg/mL) and 2.60% (0.05
      microg/mL). Inter-day accuracy showed deviations between 0.4% (0.05 microg/mL)
      and -4.8% (0.2 microg/mL). The method is simple and robust, and has been applied
      to the batch analysis of clindamycin during a pharmacokinetic study.

PMID- 12512093
TI  - Classification of green coffee beans by differences in protein composition
      obtained by matrix-assisted laser desorption/ionization mass spectrometry.
AB  - It is well known that proteins and peptides play an important role in the flavour
      of roasted coffee, but little is reported in the literature about their
      characterization. In view of the potential of matrix-assisted laser
      desorption/ionization mass spectrometry in the analysis of proteins in complex
      mixtures, two varieties of coffee green beans, Arabicas and Robustas, were
      analyzed by this technique, in order to obtain fingerprints of their native
      proteins. Differences were observed between Arabicas and Robustas green beans,
      and cluster analysis allows differentiation of samples of the same variety from
      different plantations.

PMID- 12512094
TI  - Fragmentation study of salinomycin and monensin A antibiotics using electrospray
      quadrupole time-of-flight mass spectrometry.
AB  - The fragmentation pathways of two selected ionophore antibiotics, salinomycin and
      monensin A, were studied using electrospray (ES) orthogonal acceleration
      quadrupole time-of-flight mass spectrometry in positive-ion mode. The identity of
      fragment ions was determined by accurate-mass measurements. In ES mass spectra,
      ion signals of relatively high intensity were observed for [M+Na](+) and [M
      H+2Na](+) for each antibiotic. Each of the ion species [M+Na](+) and [M-H+2Na](+)
      for salinomycin and [M-H+2Na](+) for monensin A were isolated in turn and
      subjected to fragmentation. In the fragmentation of [M+Na](+) and [M-H+2Na](+)
      from salinomycin, only Cbond;C single bond cleavage and dehydration were
      observed. Product ion mass spectra obtained from [M-H+2Na](+) of monensin A
      showed that ether ring opening, Cbond;C single bond cleavage and dehydration
      fragmentations had occurred. Fragment ions containing two sodium atoms were
      observed in the product ion mass spectrum of [M-H+2Na](+) from salinomycin, but
      not from monensin A. Both type A (containing the terminal carboxyl group) and
      type F (containing the terminal hydroxyl group) fragment ions were observed in
      the product ion mass spectra of sodium adduct ions of salinomycin and monensin A.

PMID- 12512095
TI  - A top down approach to protein structural studies using chemical cross-linking
      and Fourier transform mass spectrometry.
AB  - Mass spectrometric analysis of wild-type proteins that have been covalently
      modified by bifunctional cross-linking reagents and then digested proteolytically
      can be used to obtain low-resolution distance constraints, which can be useful
      for protein structure determination. Limitations of this approach include time
      consuming separation steps, such as the separation of internally cross-linked
      protein monomers from covalent dimers, and a susceptibility to artifacts due to
      low levels of natural and man-made peptide modifications that can be mistaken for
      cross-linked species. The results presented here show that when a crude cross
      linked protein mixture is injected into an electrospray ionization Fourier
      transform mass spectrometry (ESI-FTMS) instrument, the cross-link positions can
      be localized by fragmentation and mass spectrometry on the 'gas-phase purified'
      singly internally cross-linked monomer. Our results show that reaction of
      ubiquitin with the homobifunctional lysine-lysine cross-linking reagent
      dissuccinimidyl suberate (DSS) resulted in two cross-links consistent with the
      known ubiquitin tertiary structure (K6-K11 and K48-K63). Because no protein or
      peptide chemistry steps are needed, other than the initial cross-linking, this
      new top down approach appears well suited for high-throughput experiments with
      multiple cross-linkers and reaction conditions. Published in 2002 by John Wiley &
      Sons, Ltd.

PMID- 12512096
TI  - Performance of an ultra-low elution-volume 96-well plate: drug discovery and
      development applications.
AB  - Recently, sample preparation has been considered to be the major cause of
      bottlenecks during high-throughput analysis. With the assistance of robotic
      liquid handlers and the 96-well plate format, more samples can be prepared for
      subsequent liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis.
      Protein precipitation is still widely used despite potential loss of sensitivity
      or variable results due to ion suppression. The use of solid-phase extraction
      (SPE) clearly gives superior results but may not be as cost effective as protein
      precipitation due to the labor and material costs associated with the process.
      Here, a novel 96-well SPE plate is described that was designed to minimize the
      elution volume required for quantitative elution of analytes. The plate is packed
      with 2 mg of a high-capacity SPE sorbent that allows loading of up to 750 microL
      of plasma, while the novel design permits elution with as little as 25 microL.
      Therefore, the plate offers up to a 15-fold increase in sample concentration. The
      evaporation and reconstitution step that is typically required in SPE is avoided
      due to the concentrating ability of the plate. Examples of applications in drug
      discovery/development are shown and results are compared to protein
      precipitation. Excellent sensitivity and linearity are demonstrated.

PMID- 12512097
TI  - Analysis of isomeric long-chain hydroxy fatty acids by tandem mass spectrometry:
      application to the diagnosis of long-chain 3-hydroxyacyl CoA dehydrogenase
      deficiency.
AB  - Acetyl trimethylaminoethyl ester iodide derivatives have been used to selectively
      analyze isomeric long-chain hydroxy fatty acids by electrospray ionization tandem
      mass spectrometry (ESI-MS/MS). The binary derivatives of 2-, 3-, 12- and 16
      hydroxypalmitic acids afford remarkably different product ion spectra. Further
      discrimination between isomers is possible by acylating with pivaloyl chloride. 2
      and omega-Hydroxy long-chain fatty acids form pivaloyl esters in quantitative
      yield whereas other secondary alcohols only partially react. Cotton-based filter
      paper used for blood collection contains substantial amounts of esterified long
      chain hydroxy fatty acids. From the product ion spectra of the acetyl
      trimethylaminoethyl esters the hydroxydocosanoic and -tetracosanoic acids are
      >90% omega-hydroxy. All remaining saturated and unsaturated hydroxy acids are
      >90% 2-hydroxy acids. A method for the quantification of free 3-hydroxypalmitic
      acid in plasma by ESI-MS/MS for the diagnosis of long-chain 3-hydroxyacyl CoA
      dehydrogenase deficiency (LCHAD) is described. Median plasma concentrations of
      0.43 micromol/L (control, n = 22) and 12.2 micromol/L (LCHAD, n = 3) were
      obtained from 5 microL plasma samples.

PMID- 12512098
TI  - The relationship of the ischial tuberosity to the weight-bearing point in
      conventional above-knee prostheses.

PMID- 12512099
TI  - A contribution to the investigation by light and electron microscope of
      Langerhans islets of the carp (Cyprinus carpio L.).

PMID- 12512100
TI  - Cellular proliferation in the central nervous system of chick embryos. V. The
      influence of the extent of the peripheral innervation field.

PMID- 12512101
TI  - A contribution to the ultrastructure of the nucleus ventromedialis hypothalami in
      the cat.

PMID- 12512102
TI  - Chick embryo with two hypophyses and several other malformations on the head.

PMID- 12512103
TI  - A contribution to the problem of histogenesis of the esophageal epithelium in
      mammals.

PMID- 12512104
TI  - A methodical contribution to the study of parafollicular cells of the thyroid.

PMID- 12512105
TI  - Positive one-stage carbon replica of surface of biological suspensions.

PMID- 12512106
TI  - Cytology of tubal epithelium. II. On the question of clear cells.

PMID- 12512107
TI  - Morphology of nerve cells and fibers of a sewer rat in hypothermy. I. Nerve cells
      and fibers of the spinal cord.

PMID- 12512108
TI  - Fixing of small specimens cleared in methylsalicylate for photographing by means
      of stereomicroscope.

PMID- 12512109
TI  - Secretory manifestations of the glomus cell.

PMID- 12512110
TI  - The finding of three differently reacting types of cell nuclei in cell cultures
      using one method.

PMID- 12512111
TI  - A cinemicrographic observation of bi-nucleated HeLa cells formation.

PMID- 12512112
TI  - The ultrastructure of the epithelium of the human trachea and large bronchi.

PMID- 12512114
TI  - Contribution to the use of methacrylate in the investigation of the vascular
      architecture.

PMID- 12512113
TI  - Todaro's tendon in the heart. II. Todaro's tendon in human hearts affected by
      certain developmental anomalies.

PMID- 12512115
TI  - Sensory corpuscles in the upper lip of some artiodactyla.

PMID- 12512116
TI  - The ultrastructure of the epithelium of the respiratory bronchioles of the cat.

PMID- 12512117
TI  - Tissue shifts in the end and tail bud of the chick embryo.

PMID- 12512118
TI  - [Proton MR spectroscopy (1H-MRS): clinical usefulness for MR diagnosis of central
      nervous system].

PMID- 12512119
TI  - [Three-dimensional CT angiography of central nervous system].
AB  - Three-dimensional CT angiography (3 D-CTA) has become a modality of choice for
      the evaluation of the lesions and diseases of central nervous system. Further
      enhancement of diagnostic capability has been achieved by the development and
      introduction of multislice CT, which enabled us to obtain true isotrophic
      volumetric data. Most proven application of 3 D-CTA in CNS is the diagnosis and
      management of cerebral aneurysms. It can be used as an alternative to
      conventional angiography in most of cases. Other promising applications of 3 D
      CTA are, pre-surgical evaluation of arteriovenous malformations, diagnosis of
      ischemic diseases, and evaluation of neck artery.

PMID- 12512120
TI  - [CT perfusion: basic principles and clinical application].

PMID- 12512121
TI  - [Newly developed techniques for brain function imaging using SPECT].

PMID- 12512122
TI  - [Measurement of brain function by positron emission tomography: from mapping to
      synaptic function].

PMID- 12512123
TI  - [Neurosonologic examination].

PMID- 12512124
TI  - [Clinical study of percutaneous endoscopic gastrostomy in neurosurgery].
AB  - We investigated the efficacy of percutaneous endoscopic gastrostomy (PEG) in
      neurosurgery. PEG was applied 94 feeding patients using One-Step Button. The mean
      age was 70.8 +/- 15.4 years old, and the mean duration between the onset of
      swallowing disturbance and PEG was 3 months. Minor complication associated with
      PEG was 8 cases (8.5%), which treated conservatively. Body weight, BMI, and
      biochemical data were increased one month after PEG, so nutrition was improved.
      Aspiration pneumonia was improved in 9/18 patients. Fourteen patients got oral
      intake, and PEG was extracted in 10 patients. PEG was evaluated to be superior to
      transnasal feeding with regard to simplicity, efficacy, improvement of good
      nutrition or aspiration pneumonia, and rehabilitation.

PMID- 12512125
TI  - [A case of spontaneous intracranial hypotension without any history of positional
      headache].
AB  - A 52-year-old woman was admitted to our hospital with sudden diplopia, right
      ophthalmalgia, and occipital pain. The nature of her headache was continuous, and
      changing her position provided no relief. Three weeks before her admission, she
      experienced continuous cough and rhinorrhea during a few days. On admission, her
      neurological examination revealed right abducens paralysis, and right lateral
      gaze aggravated diplopia. Brain magnetic resonance imaging scan demonstrated
      diffuse pachymeningeal enhancement by gadolinium. Radioisotope cisternography
      showed a leak of cerebrospinal fluid from near the third lumbar vertebra. The
      first lumbar puncture revealed an initial pressure of 0 mm H2O. She was given a
      diagnosis of spontaneous intracranial hypotension due to a leak of the
      cerebrospinal fluid. During her hospitalization, she complained of vertigo and
      nausea. We found horizontal gaze nystagmus to left side and sensorineural
      deafness in her left ear, which improved in a few days. After treatment by a
      lumbar epidural continuous infusion of saline and a lumbar epidural blood patch,
      her headache and abnormal MRI findings had improved. The continuous cough before
      her admission may be the cause of the leak of cerebrospinal fluid. We had
      difficulty in diagnosis only by the history and clinical examination, because she
      had no history of orthostatic headache.

PMID- 12512126
TI  - [A case of retrobulbar optic neuritis associated with Sjogren syndrome which
      remitted spontaneously].
AB  - A 21-year-old woman came to the department of ophthalmology because of decreased
      visual acuity detected at the driving license center. MRI revealed T 1 iso-, T 2
      hyper-intense, and Gd-enhanced lesion in the left optic nerve adjacent to the
      optic chiasma. No autoantibodies indicating systemic lupus erythematosus, Sjogren
      syndrome, or anti-phospholipid syndrome were elevated except for antinuclear
      antibody. There were no cerebral and spinal lesions on MRI. Neither oligoclonal
      IgG band nor myelin basic protein was found in the cerebrospinal fluid. Although
      she did not complain of dry mouth, secretion of the saliva was decreased. Biopsy
      of the minor salivary gland showed sialadenitis with infiltration of mononuclear
      cells, suggesting subclinical Sjogren syndrome. Visual acuity and MRI findings
      were remitted spontaneously. This case is distinguished from multiple sclerosis
      and vasculitis or ischemic mechanism(s) associated with autoantibodies might play
      a role in the development of the disease.

PMID- 12512127
TI  - [Hypoplasia of internal carotid artery at cervical portion associated with
      neurofibromatosis type I].
AB  - Congenital absence of the internal carotid artery (ICA) is a rare anomaly and
      aplasia/hypoplasia of the ICA associated with other congenital malformations is
      uncommon, too. We report a very rare case of hypoplastic carotid canal due to
      hypoplastic ICA at cervical portion associated with neurofibromatosis type I (NF
      I). A 22-year-old male with NF I was admitted to our hospital for transient
      weakness of the left upper and lower limbs. Computed tomography (CT) of the brain
      demonstrated no abnormal findings. But bone target CT and three dimensional
      computed tomography (3 D-CT) showed a hypoplasia of right carotid canal. Cerebral
      angiography revealed that the right ICA was hypoplastic at its cervical portion
      and occluded at the carotid canal. Rest single photon emission computed
      tomography (SPECT) demonstrated normal cerebral perfusion, and SPECT with
      acetazolamide demonstrated showed cerebral perfusion reserve of both hemispheres,
      too. So he was treated conservatively at the present time. Careful follow up
      should be performed for such patients, because they are very rare cases and the
      natural history of them is unknown, too.

PMID- 12512128
TI  - [A case of focal epilepsy associated with focal cortical dysplasia and crossed
      cerebellar diaschisis].
AB  - We here reported a 24-year-old woman who presented complex partial seizure from
      15 years of age. Her brain MRI showed the right perirolandic focal cortical
      dysplasia (FCD) corresponding to the orofacial division of the primary sensori
      motor area. On SPECT (Tc-99 mECD) study, hypoperfusion was demonstrated at the
      FCD, the right pons and the left cerebellum (crossed cerebellar diaschisis
      (CCD)). Magnetoencephalography disclosed the current source of the focal spikes
      was localized on the FCD. To our knowledge, no previous report of a case
      associated with FCD and CCD was found. We speculated the pathomechanism of the
      CCD might be related to the persistent epileptogenic firing which inhibited the
      cerebellar metabolism transsynaptically through cortico (FCD)-ponto-cerebellar
      pathway.

PMID- 12512129
TI  - [A case of heterotopic gray matter incidentally diagnosed before epileptic
      seizure].

PMID- 12512130
TI  - [Enlargement of pituitary gland with spontaneous intracranial hypotension].

PMID- 12512131
TI  - [Stress management in hospitals].
AB  - Job stress in employees in hospitals has been recognized as a key issue in the
      workplace. In this paper, characteristics of job stress in the medical
      profession, especially in doctors and nurses, and the effectiveness of stress
      management are overviewed. The important points in stress management in hospitals
      are summarized as follows: 1) improvement of work environment, 2) assurance of
      participation and autonomy, 3) education or training to reduce job stress (ex.
      coping behavior, self-care, relaxation), 4) career development, 5) total support
      among medical professions. Some reports have demonstrated that the establishment
      of constant meetings is an effective method of reducing job stress and improving
      mental health in the medical profession, but few prospective intervention studies
      have been carried out. Further research is necessary to evaluate the
      effectiveness of stress reduction and to develop effective intervention programs
      for medical professions in hospitals.

PMID- 12512132
TI  - [The present state and forthcoming problems in the work of occupational health
      physicians engaged in the workplace].
AB  - The authors conducted a survey in July 2001 to examine the present state and
      forthcoming problems facing occupational health physicians (OHPs). The
      establishments investigated were those which employed 1,000 or more workers and
      had consulted us for the employment of OHPs. The number of establishments chosen
      was 1,658. A questionnaire was sent to the division chiefs responsible for the
      health management of the establishments, and those who supervised the OHPs
      engaged in the establishments were asked to complete the questionnaire. The
      questionnaire included items about the attributes of the perspective
      establishments, the work of OHPs and the personnel management system for the
      OHPs. Four hundred and forty-seven establishments (27.0%) out a total of 1,658
      returned eligible responses for further analysis, and the major results were as
      follows: First, 79.2% of the manufacturing establishments which responded
      comprised those which employed 1,000 or more workers, even though the percentage
      of companies which employ 1,000 or more workers throughout Japan is 62.5%. The
      percentage of the establishments which employed full time OHPs was 64.2% in
      secondary industries (mining, constructing and manufacturing), and higher than
      the 40.8% in tertiary industries (other than farming, forestry, fishing and
      secondary industries). Second, although OHPs properly coped with the obligatory
      issues regulated by the related laws, the OHPs who routinely consulted with
      workers about their work-related health problems were few (36.7%). Third, despite
      the low percentage of the establishments (23.5%) which had recognized OHPs' work
      to be part of enterprise management, the budget of the health care section was
      kept unchanged (55.0%). And, in 49.0% of the establishments, the nomination of
      OHPs was recognized to be necessary irrespective of the presence of the related
      laws, and OHPs were expected to cope with the work-related health problems of
      workers (62.9%). On the other hand, the personnel management system for OHPs was
      insufficient, and the performance rating for OHPs' activity was prepared for only
      50.3% of the establishments. In addition, when the subjects were confined to
      regular OHPs, they were allowed to attend internal training courses for regular
      employees in only 25.0% of the establishments. Taking the above into account, the
      activity of OHPs has to be developed more in tertiary industries. OHPs may also
      be asked to positively cope with workers' work-related health problems.
      Simultaneously, the personnel management system for OHPs has to be arranged
      properly.

PMID- 12512133
TI  - [An example of psychometric validation of a mental health questionnaire used at a
      work place].
AB  - Most companies utilize original questionnaires developed by the health-care staff
      to evaluate their workers' mental health status. To build effective strategies,
      it is crucial to use proper measures validated psychometrically. We demonstrated
      the process to evaluate the reliability and validity of the original health
      questionnaire developed by the health-care team of an industrial company. We used
      the Beck Depression Inventory-II, and the Job Content Questionnaire as the gold
      standards for external validation. Out of 21 items in the original health
      questionnaire, 9 items significantly correlated with depression. From the results
      of a factor analysis, the 9 items composed 2 independent components out of 5
      factors. A subscale which consisted of the 9 items from the original
      questionnaire was proposed as a screening tool to detect depression, but no items
      of the original questionnaire correlate with the Support subscale nor the Job
      Control subscales of the JCQ. Just one item correlated with the Job Demand
      subscale of the JCQ. Additional information should be added to the original
      questionnaire to evaluate Job Stress based on the Karsek's Job Demand-Control
      Support model.

PMID- 12512134
TI  - [Investigation of the health condition of the "shukko" person in a certain
      Japanese company].
AB  - The influence of the "shukko" (temporary transfer) work system on health was
      examined. "Shukko" is a Japanese individual work system. The life-time employment
      system was general in Japan. "Shukko" work system was devised to reduce the
      number of personnel in Japan. "Shukko" personnel belong to their present company
      but they must do the work of another company. Generally, the disadvantages of
      "shukko". Personnel are greater than in former "shukko" The subjects are 483
      office workers in a certain industrial company. 143 workers work in a subsidiary
      of this company (Age: 42.2 +/- 5.5) (strategic shukko group), 30 workers work in
      the other company, having resigned their administrative post in the head office
      (55.6 +/- 2.1) (Demotion by the manager shukko group), and 310 workers work in
      the head office of this company (41.8 +/- 5.2) (head office working group). The
      medical examination results (degree of obesity, systolic blood pressure (SBP),
      GPT, GGTP, total cholesterol, triglyceride (TG), fasting blood sugar (FBS), uric
      acid (UA), electrocardiography (ECG), and gastrography were compared by mean of
      multiple regression analysis. In the "Demotion by the manager shukko" group, the
      average age and SBP were higher than in the other groups. (p < 0.0001). The
      "strategic shukko" group was compared with the "head office working" group. There
      is no significant difference in average age. The average SBP (p < 0.001) and FBS
      (p < 0.0001) of the "head office working" group was significantly higher than
      those of the "strategic shukko" group. ECG findings were more serious in the
      "Demotion by the manager shukko" group than in the other groups (p < 0.0001).
      There is a significant correlation between SBP and "degree of obesity, FBS and
      UA" (p < 0.0001). There is significant correlation between FBS and "GGTP, SBP,
      UA, GPT and TG" (p < 0.0001). And there is significant correlation between ECG
      findings and "working form and SBP" (p < 0.05). The prevention and early
      diagnosis of geriatric diseases is important for the "Demotion by the manager
      shukko" group, and their average age is older than that of the other groups. A
      problem with the head office working group is obesity. In this group it is
      important to take into consideration life related diseases. The workers complaint
      a lot in the "strategic shukko" group, but there are no abnormal findings. We
      think that their complaints are due to their mental stress. In this group
      measuring mental stress is important.

PMID- 12512135
TI  - Distribution of cathepsin D granules in normal and pathologic conditions in human
      prostate.
AB  - Although cathepsin D has been implicated in prostate cancer invasion and
      metastasis, the distribution of this enzyme in normal human prostate is unknown.
      We investigated immunohistochemically the distribution of cathepsin D granules in
      normal prostatic tissues with or without androgen ablation. We also examined the
      cancer tissues after androgen ablation and the hyperplastic tissues. Changes in
      the distribution pattern of the larger cathepsin D-positive granules (apoptotic
      bodies) were observed in the normal prostate as well as in the normal tissue of
      the anti-androgen-treated cancer specimens. While the apoptotic bodies were
      denser in the proximal duct of the normal adult prostate, they were more abundant
      in the normal peripheral acini of the anti-androgen-treated cases. There were few
      apoptotic bodies in the adenoma tissues, but many in the hormonally treated
      cancer tissues. These results showed that the distribution pattern and density of
      cathepsin D granules well reflected the status of the human prostatic cells in
      relation to age, hormonal environment and hyperplastic or neoplastic change.

PMID- 12512136
TI  - [A fact-finding inquiry on urinary management of the elderly in home care].
AB  - A fact-finding inquiry was made on elderly people in home care, in order to
      investigate urinary management. A questionnaire survey was performed on 2,322
      elderly people (1,023 male and 1,299 female) cared at home by 40 home nursing
      stations in Aichi prefecture. The survey focused on the urinary management and
      the practical problems at home. The number of the elderly managed by an
      indwelling catheter was 225 (9.7%) and 1,301 (56.0%) of the elderly wore diapers.
      The rates of the people managed by an indwelling catheter or diapers widely
      varied among the home nursing stations. In 25.3% of the people managed by an
      indwelling catheter, the catheter was used because of urinary incontinence, which
      should not normally be indicated. Diapers were unnecessarily used in 23.9% of
      people mainly for a protective purpose. The majority of the people whose voiding
      dysfunction was managed either by an indwelling Foley catheter or diapers had had
      this treatment started before discharge from hospital. Only 5.8% of the elderly
      wearing diapers received consultation from medical specialists. Intermittent
      catheterization was performed in 36 people (1.6%), and in 23 (63.9%) the
      catheterization was carried out by the care givers. We conclude that the urinary
      management in the elderly cared at home is insufficient and that standardization
      of the urinary management and creation of a network of care givers, nurses,
      general physicians, medical specialists and government representatives should be
      urgently needed to improve the quality in urinary management in the elderly.

PMID- 12512137
TI  - [Skin necrosis of the penis due to strangulation to which mesh skin grafting was
      performed: a case report].
AB  - A 79-year-old man visited our hospital for strangulation of the penis. There was
      local infection and necrosis on the penile skin. After debridement of the
      necrotic tissue and conservative therapy, we performed mesh skin grafting. Skin
      epithelialization was good after operation.

PMID- 12512138
TI  - [Erectile dysfunction arising from polyarteritis nodosa: a case report].
AB  - A 30-year-old male was referred to our department during the examination and
      treatment for hypertension, because he had not achieved complete erection since
      the age of 26 years. After detailed examination, he was diagnosed to be suffering
      from nodal polyarteritis. Since erectile dysfunction persisted, the patient was
      hospitalized to investigate the cause of erectile dysfunction. Measurement of the
      penile brachial index (PBI) and cavernous infusion of papaverine hydrochloride
      strongly suggested the presence of arterial erectile dysfunction. Internal
      pudendal angiography revealed multiple microaneurysms in the bilateral internal
      pudendal arteries, suggesting that nodal polyarteritis caused arterial erectile
      dysfunction.

PMID- 12512139
TI  - [A case of adrenal cortical carcinoma].
AB  - We report a case of left adrenocortical carcinoma in a 23-year-old man. His chief
      complaints were spike fever attack and general malaise. Imaging examination
      revealed a heterogeneously enhanced mass at the site of the left adrenal gland.
      Non-functional adrenocortical carcinoma was suspected from hormonal studies. The
      mass was removed together with the left kidney because of severe adhesion to the
      renal pedicle. The histopathological findings showed adrenocortical carcinoma
      (pT3N0M0). Three months after surgery, local recurrence appeared and the tumor
      grew larger rapidly. Spike fever attack reappeared. No distant metastasis was
      detected. Two courses of systemic chemotherapy with o, p'-DDD, VP-16, adriamycin
      and cisplatinum were performed. Computed tomography after the chemotherapy showed
      progression. Although o, p'-DDD was administered continuously, the patient died
      of cancerous cachexia 8 months after the surgery. Autopsy could not be done.

PMID- 12512140
TI  - [Pathogenesis of chronic renal allograft dysfunction].
AB  - The pathogenesis of chronic renal allograft dysfunction was reviewed. Chronic
      rejection/chronic renal allograft nephropathy is the most prevalent cause of
      renal graft loss after the first year post-transplant. Both immunologic and non
      immunologic factors play key roles in the pathogenesis of chronic allograft
      nephropathy. Acute rejection episodes are the most prevalent risk factor for
      chronic rejection. Many risk factors for chronic allograft nephropathy have been
      identified, such as glomerular hyper-filtration, delayed graft function, repeated
      acute rejection, systemic hypertension and hyperlipidemia. However, the precise
      pathogenesis of chronic allograft nephropathy remains obscure. The differential
      diagnosis of immunologically mediated chronic rejection and chronic allograft
      dysfunction caused by non-immunologic factors is usually impossible using
      clinical parameters. The histopathologic findings of chronic allograft
      nephropathy are progressive interstitial fibrosis with tubular atrophy and
      thickening of vascular intima, and these findings are non-specific. Therefore,
      the term chronic allograft nephropathy may be clinically preferable to chronic
      rejection to describe the gradual decline in graft function. The most effective
      way to prevent chronic allograft dysfunction is to avoid any kind of graft damage
      via immunologic or non-immunologic pathway.

PMID- 12512141
TI  - [Chronic allograft nephropathy: its diagnosis and treatment].
AB  - The process of chronic allograft nephropathy (CAN) is primarily concerned with
      disparity in major histocompatibility. However, changes similar to CAN have been
      seen in human kidney transplants between identical twins, as well as in rat
      kidney isografts. Such changes cannot be explained by antigen-dependent factors;
      antigen-independent factors are likely to be involved in the onset of CAN. A CAN
      type picture also was seen in a rat single kidney model subjected to ischemic
      injury, indicating the importance of ischemia in the process of CAN. In the
      present study, CAN was accelerated by renal ablation in a rat kidney transplant
      model with reduced nephron number. Conversely, recipients with increased renal
      mass bearing two allografts, did not show any signs of CAN. These observations
      suggested that a non-allogenic factor such as ischemia and insufficient nephron
      number is critical in the development of CAN, and thus the etiology of CAN is
      hypothesized as follows. Many factors such as ischemic injury, acute rejection or
      infection reduce the functioning nephron number, which causes hyperfiltration in
      remaining nephrons leading to glomerulosclerosis. This in turn, further reduces
      the functioning nephron number. These progressive events may reinforce further
      the stimulus of hyperfiltration, thereby establishing a self-sustaining vicious
      cycle. Any factor preventing the reduction of functioning nephron number, can be
      a candidate for treatment. Herein, we showed that treatment with hepatocyte
      growth factor (HGF), a renotropic factor, in the initial disease stage prevented
      further development of CAN.

PMID- 12512142
TI  - [Immunological factors for chronic rejection and the methods for the prevention
      of chronic allograft nephropathy].
AB  - For the prevention of the immunological chronic rejection, HLA-DRB1 allele
      matching, enough immunosuppression in the induction phase and pathological
      diagnosis by non-episode and protocol biopsy are the effective methods. For the
      prevention of the non-immunological chronic rejection, treatments for
      hypertension, hyperlipidemia and hyperfiltration are the effective treatments.

PMID- 12512143
TI  - [Effect of acute rejection episode on occurrence of chronic rejection after
      kidney transplantation].
AB  - Chronic rejection is the most prevalent cause of renal transplant failure in the
      late post-transplant period. The clinical significance of acute rejection
      episodes on occurrence of chronic rejection is controversial. We analyzed 503
      cases of the first renal transplantation maintained by calcinurine inhibitor for
      the correlation of acute rejection and clinical chronic rejection. The later the
      first episode of acute rejection occurred, the shorter was the half-life of
      graft. The acute rejection occurring within 3 post-transplant months worsens long
      term graft survival if the peak creatinine level exceeds 2 mg/dl. Multivariate
      analysis by the Cox proportional hazard model for factors affecting cadaver graft
      loss by chronic rejection, revealed that the risk factor of acute early rejection
      was lower than those of donor age and post-transplant hypertension.

PMID- 12512144
TI  - [Non-immunological risk factors associated with chronic allograft nephropathy
      following kidney transplantation].
AB  - Although the precise mechanisms are unclear, not only alloantigen-dependent but
      also antigen-independent factors are generally thought to influence the
      development of chronic allograft nephropathy (CAN). Among the non-immunological
      determinants, there are various factors related with donor, recipient and graft
      procurement. As donor factors, age and cause of death were demonstrated to be
      significantly independent in long-term graft survival of cadaveric kidney
      transplantation. Grafts from aged donors and from donors with athelosclerosis
      showed poor prognosis on graft survival. Regarding recipient factors,
      cardiovascular complications, as hypertension and hyperlipidemia, were
      responsible for graft as well as patient survival. In addition, CMV infection and
      drug nephrotoxicity were also shown to affect graft survival. For procurement
      factors, warm ischemia was determined to possess the strongest impact on long
      term graft survival in our series of kidney transplant using grafts from non
      heart beating donors (NHBDs). Delayed graft function, which correlated well with
      length of warm ischemia, also influenced long-term graft survival. These results
      proved that the supply of viable donor nephrons and the physiologic demands of
      the recipient are important determinants of long-term graft survival. So far
      there seems to be neither definitive nor specific treatment for CAN. It is
      basically essential to avoid graft damage before transplant and keep recipients
      from risk factors after transplant as much as possible. To improve long-term
      graft survival in cadaveric kidney transplantation, recipient selection is
      greatly important in terms of not only immunological compatibility but also body
      to nephron mass imbalance and ischemic time, which might cause fatal damage to
      grafts before engraftment.

PMID- 12512145
TI  - [Non-immunologic factor: immunosuppressive drug-induced nephrotoxicity].
AB  - Immunosuppressant-induced nephrotoxicity contributes to kidney graft loss in the
      long-term as one of the non-immunologic factors. We previously reported that
      correction of cyclosporine A (CsA)-induced hypomagnesemia reduced chronic CsA
      nephrotoxicity. This study was conducted to elucidate the mechanism of the
      beneficial effects of magnesium (Mg) on CsA nephrotoxicity and examine the role
      of the renin-angiotensin system in this mechanism. We particularly focused on CsA
      induced interstitial mononuclear cell infiltration. CsA (15 mg/kg/day, s.c.) was
      administered daily to rats maintained on low sodium diets for 7, 14 and 28 days.
      The inhibitory effects of Mg supplementation and those of angiotensin converting
      enzyme inhibitor (ACEI) were compared for renal function, renal histology,
      mononuclear cell infiltration and gene expression profile. CsA lowered creatinine
      clearance and developed characteristic tubulointerstitial fibrosis that were
      mostly evident at day 28. CsA-induced impairment of renal function was
      ameliorated by Mg supplementation but not by ACEI. Monocyte/macrophage
      infiltration preceded the renal fibrosis and increased progressively with the
      duration of CsA administration. CsA markedly upregulated the expression of
      chemoattractant proteins, osteopontin and monocyte chemoattractant protein-1,
      concomitantly. These changes were markedly attenuated by Mg but only slightly by
      ACEI. CsA also promoted expression of fibrogenic molecules and extracellular
      matrices that were markedly attenuated by Mg but only slightly by ACEI.
      Similarly, CsA-induced tubulointestitial fibrosis was almost completely abolished
      by Mg supplementation but only partially attenuated by ACEI. These results
      suggested that Mg supplementation abolished CsA-induced precedent inflammatory
      cell influx possibly via inhibition of expression of chemoattractants and
      consequently suppressed tubulointerstitial fibrosis. In this beneficial
      mechanism, factors independent of renin-angiotensin system seem to be mainly
      involved.

PMID- 12512146
TI  - [Mechanisms of prostate cancer recurrence].
AB  - Androgen-deprivation therapy is often the first choice of several therapeutic
      procedures for advanced prostate cancer. However, despite an initial response to
      androgen-deprivation therapy, the cancer eventually progresses from an androgen
      dependent to an androgen-independent phenotype. Molecular mechanism of
      development to androgen-independence and recurrence during androgen-deprivation
      therapy remain unclear. The observation that heterogeneity of AR expression in
      prostate cancer correlates with malignancy suggests that androgen responsiveness
      plays an important key role in the progression of prostate cancer. Therefore, it
      is very important to consider the role of AR and mechanisms of relapse when we
      treat androgen-independent prostate cancer.

PMID- 12512148
TI  - [Clinicopathological significance of neoadjuvant hormonal therapy prior to
      radical prostatectomy: whole section analysis].
AB  - We investigated whether the histopathological effect (cell viability) of
      neoadjuvant hormonal treatment before radical prostatectomy for clinically
      localized prostate cancer is involved in the biochemical outcome, i.e., androgen
      independency. Non-randomized prospective trial was carried out between September
      1996 and April 2001 involving the patients with clinical stage T1-3 prostate
      cancer, including 62 who underwent radical prostatectomy after receiving
      neoadjuvant hormonal treatment for an average of 6.3 months and 76 who underwent
      radical prostectomy only. All resected specimens were histopathologically
      diagnosed by whole section analysis. The patients receiving neoadjuvant hormonal
      treatment were categorized into 4 groups according to the histological change in
      the resected prostate. There were 8 patients in G0 (all viable cells), 11
      patients in G1 (more than 50% viable cells), 26 patients G2 (more than 50% non
      viable cells) and 17 patients in G3 (no cancer cells). No difference in the
      patient background (prostate specific antigen, stage, Gleason score, positive
      core Nr, duration of neoadjuvant therapy) was observed in any group, except for
      the duration of (p < 0.05). Multivariate hazards analyses revealed that only the
      duration of neoadjuvant hormonal treatment was independently associated with
      excellent responders with grade 3 histological effect. Neoadjuvant hormonal
      therapy prior to radical operation resulted in various histopathological changes
      in the prostate, but it is not clear whether the histological effects of hormonal
      treatment might be involved in the outcome. A longer follow-up randomized
      prospective trial is necessary.

PMID- 12512149
TI  - [Laminectomy for spinal cord compression occurring in hormone refractory prostate
      cancer].
AB  - In many cases of advanced prostate cancer, bone metastasis frequently occurs.
      Androgen deprivation therapy is very effective for these cases, but this therapy
      would result in failure, and symptomatic metastasis would develop. Approximately
      eighty percent of cases with bone metastasis showed epidural metastasis. When
      these lesions enlarge, spinal cord compression (SCC) occurs in five to ten
      percent of cases. Many urologist would choose an adequate modality for this
      problem, based on the prognosis and/or general status of each patient. In this
      article we overview laminectomy for SCC and present our experience.

PMID- 12512147
TI  - [Hormonal chemotherapy for hormone-refractory prostate cancer].
AB  - To our knowledge, no standard chemotherapy for patients with hormone-refractory
      prostate cancer (HRPC) has been established. Since most patients with HRPC are
      elderly and have bone metastasis, cytotoxic chemotherapy causes them to be at
      high risk for myelosuppression. Therefore, chemotherapeutic agents with low
      toxicity and good compliance should be elected. We conducted three regimens for
      HRPC on an outpatient basis. Eligibility criteria were defined as serial rising
      PSA values on 3 or more occasions at least 2 weeks apart or radiological new or
      extensive lesions under hormonal therapy. The first regimen is comprised of
      cyclophosphamide (CPM), 100 mg/day, UFT, 400 mg/day, and estramustine phosphate
      (EMP), 560 mg/day in two daily fractions. The second regimen is comprised of an
      oral administration of dexamethasone (DEX) (0.5-2 mg/day). The third regimen is
      comprised of DEX, 1 mg/day, cyclophosphamide, 100 mg/day and UFT, 400 mg/day in
      two daily fractions. Post-therapy prostate-specific antigen (PSA) level in serum,
      objective response on bone scan or measurable disease, and symptomatic response
      on bone pain were assessed. All regimens showed clinical efficacy with mild
      toxicity. Indications and limitations of these regimens are discussed. Further,
      the combination trials of taxane and EMP in patients with HRPC are reviewed.

PMID- 12512151
TI  - Pharmacy and health care.

PMID- 12512150
TI  - [Gene therapy for prostate cancer].
AB  - The substantial advances made in recent years in the molecular biology of
      malignant urological tumors and the associated progressive analysis of these
      conditions at a molecular level have spurred research aimed at gene-based
      treatment. In the field of prostate cancer, while there have been many ground
      breaking studies particularly in the United States, none has yet led to a
      revolutionary treatment for recurrent prostate cancer. Gene-based treatment is
      being applied seriously in clinical settings, especially in the United States,
      but so far without significant effect. Many researchers worldwide are devoting
      energy to the development of effective vectors. By adjusting the promoter, which
      has the function of directing the vector, we have developed organ-specific
      vectors for the treatment of prostate cancer. In the present study, which
      targeted prostate cancer with bone metastasis, we developed a suicide-gene
      therapy using an adenovirus vector with an organ-specific osteocalcin promoter.
      Clinical trials of this vector have already been conducted at the University of
      Virginia in the United States and have so far confirmed the safety of the
      therapy. In the present paper we present the results of this gene-therapy
      research from the basic to the clinical phase alongside an outline of related
      research at our institution. Gene therapy for cancer is now being targeted not
      only against the primary tumor but systemic cancers including distant metastases;
      systemic administration of adenovirus vectors with organ-specific promoters may
      become one of the most promising systemic anti-tumor therapies of the next
      generation.

PMID- 12512152
TI  - Lichenoid eruption associated with cinnarizine use.

PMID- 12512153
TI  - Data collection methods for analyzing the quality of the dispensing in
      pharmacies.
AB  - OBJECTIVE: To review and discuss the advantages and limitations of the different
      data collection methods for analyzing the dispensing quality in community
      pharmacies. METHODS: A bibliographic search was carried out in MEDLINE (1980
      2000). Articles with Medical Subject Heading (Mesh) "pharmacies" written in
      English and Spanish that evaluated the quality of dispensing (structure, process
      or outcome) were selected. RESULTS: Various data collection methods were
      observed. To analyze the quality of the structure, questionnaires and pharmacist
      interviews were used. To analyze the quality of the process, self-completed
      records, external observers and simulated clients were used. For analyzing the
      quality of the outcome, questionnaires, client interviews, and biologic samples
      were collected. CONCLUSIONS: The analysis of quality of structure can be useful
      as a first approach, however, this method may lack sensitivity. On the other
      hand, the analysis of outcome may be excessively complex and difficult to use,
      except for experimental or observational studies with large resources. Therefore,
      an analysis of the quality of the process is the best option. Methods utilizing
      external observers and simulated clients may best conjugate both internal and
      external validity.

PMID- 12512154
TI  - Community pharmacists' perspectives on pharmaceutical care implementation in New
      Zealand.
AB  - OBJECTIVE: There were three objectives to this study: to establish New Zealand
      community pharmacists' level of understanding of the pharmaceutical care process,
      to determine their attitudes to the concept of pharmaceutical care; and to
      determine the barriers to commencing pharmaceutical care practice. Comparisons
      were made between proprietors (pharmacy owners) and employees, males and females,
      and younger and older pharmacists. METHOD: The research tool was a questionnaire
      instrument, encompassing a total of 67 questions designed to determine community
      pharmacists' understanding, attitudes and appreciation of the opportunities and
      barriers inherent in the pharmaceutical care process. A total of 490 pharmacists
      representing 286 proprietors and 204 employees randomly selected from the
      Pharmaceutical Society register were sent a questionnaire. RESULTS: The total
      responses numbered 377, which was a 76.9% overall response rate. Over 60% of the
      pharmacists surveyed had a correct understanding of pharmaceutical care.
      Approximately the same percentage felt the future of pharmacy would depend on the
      provision of services other than dispensing. Insufficient time, as a barrier to
      implementation, was identified by 87% of respondents, and an absence of a
      reimbursement system by a further 82%. Lack of: therapeutic knowledge; clinical
      problem solving skills; finance; appropriate space, patient demand; access to
      patient medical records, and data on the value of PC were identified as major
      barriers by over 50% of all respondents. There were significant differences in
      response to a number of issues recorded by males and females, proprietors and
      employees, and pharmacists above and below the mean sample age of 45 years.
      CONCLUSION: This study found that the community pharmacy environment in New
      Zealand had a high level of understanding of the pharmaceutical care process, but
      identified some significant barriers to implementation.

PMID- 12512155
TI  - Pharmacoeconomic evaluation of a patient education letter aimed at reducing long
      term prescribing of benzodiazepines.
AB  - OBJECTIVE: To determine the economic implications of sending an educational
      letter to patients, aimed at reducing long-term BDZ prescribing. METHOD: Letters
      were sent to 242 patients from 2 general medical practices. BDZ usage and costs
      were compared in the years before and after intervention using numbers of defined
      daily dosages (DDDs) prescribed. The cost of intervention implementation was
      estimated using pharmacist, GP and administrative staff time, plus postage costs.
      MAIN OUTCOME MEASURES: Number of BDZ DDDs prescribed during the 12-month periods
      before and after intervention. The cost implications of intervention. RESULTS:
      Mean patient age was 67 years, 75% were female and the mean duration of BDZ usage
      was 19 years. A mean of 337 benzodiazepine DDDs per patient were prescribed
      during the baseline year. Overall BDZ usage at baseline was increasing by 13%.
      After receiving the letter, 31% of patients discussed BDZ usage with their GP and
      10% had their drug or strength changed. During the year after intervention, a
      significant reduction of 17% in benzodiazepine usage was observed compared to
      baseline; 5% of patients ordered no more benzodiazepine prescriptions after
      receiving the letter. Mean BDZ costs reduced by 1.20 Pounds per patient after
      intervention. The cost of intervention implementation was 5.54 Pounds per
      patient, giving a net cost of 4.34 Pounds per patient, or 86.80 Pounds to obtain
      one BDZ discontinuation. CONCLUSION: This intervention is effective, simple, and
      inexpensive. Its minimal cost could be justified given the morbidity associated
      with the long-term prescribing of benzodiazepines, particularly in the elderly.

PMID- 12512156
TI  - The validation of an existing method of scoring the severity of medication
      administration errors for use in Germany.
AB  - OBJECTIVE: The aim of this study was to assess the validity and reliability of an
      existing method of scoring the severity of medication administration errors,
      developed in the United Kingdom (UK), for use in Germany. METHOD: 10 doctors, 10
      nurses, and 10 pharmacists from German hospitals were asked to score the
      potential clinical significance of 49 cases of medication administration errors
      on a visual analogue scale. MAIN OUTCOME MEASURE: Generalisability theory was
      used to determine the minimum number of judges required to obtain a reliable mean
      score, Validity was assessed by comparing the mean scores given by the judges to
      the known outcome of the errors for a subset of the cases. German results were
      compared to original UK data. RESULTS: The scores of 27 judges could be used
      (nine from each profession). At least three health professionals, one from each
      profession, were required to achieve a generalisability coefficient of 0.86,
      indicating acceptable reliability. The mean scores were found to be valid
      indicators of the potential severity of the errors German scores were
      significantly below UK scores for the same cases. CONCLUSION: The mean score
      calculated from scores given by one doctor, one nurse and one pharmacist from the
      population of German health professionals was a valid and reliable measure of the
      potential clinical significance of medication administration errors. That German
      health professionals see cases as less dangerous than their UK counterparts is
      worthy of further investigation.

PMID- 12512157
TI  - A qualitative study of the difficulties of smoking cessation; health care
      professionals' and smokers' points of view.
AB  - OBJECTIVE: To obtain a deeper understanding of smokers feelings and to establish
      co-operative networking groups, the opinions about smoking cessation of health
      care professionals and smokers were studied. DESIGN: Focus group discussions were
      held in order to gain ideas and tools to be used in smoking cessation work, in
      particular in network groups. Two focus group discussion for health care
      professionals (n = 7) and one focus group discussion for ex-smokers/smokers (n =
      3) were held. RESULTS: The study suggests that problems exist in smoking
      cessation work among health care professionals. The main issues among the health
      care professionals were lack of motivation and consistency of approach.
      Information concerning the health risk related to smoking no longer reaches
      people. New ways of health promotion are desired. Smokers feel that lack of
      positive support and nicotine dependence are the main problems in their attempts
      to quit. CONCLUSIONS: Society and smokers have the same goal: smoking cessation.
      However, both parties do not seem to agree on ways of achieving this goal. A
      local network among health care professionals could motivate and give rise to new
      methods of smoking cessation counselling. Positive support and nicotine
      replacement therapy could significantly improve smokers success rates. Trained
      personnel have better opportunities for meeting smokers and that is why cessation
      should be part of the core curriculum and basic training for health care
      professionals.

PMID- 12512158
TI  - Intravenous and oral antibiotics in respiratory tract infection: an international
      observational study of hospital practice.
AB  - BACKGROUND: Hospitalised patients with respiratory tract infections (RTI)
      frequently receive intravenous (i.v.) antibiotics followed by a short course of
      oral treatment. OBJECTIVES: To observe antibiotic use in hospitals in Germany,
      Spain, France, Italy and the UK and the reasons for choosing the i.v. route and
      switching to oral treatment. METHODS: Research pharmacists sought the opinions of
      physicians and senior nurses in the completion of a semi-structured questionnaire
      on the treatment of RTI with i.v. antibiotics. Questions focussed on
      antimicrobials of choice, reasons for choosing i.v., reasons for changing to oral
      administration, and duration of treatment. RESULTS: This study recruited 796
      patients with RTI, usually pneumonia. Prescribing patterns varied widely between
      the five hospitals. Accepted clinical criteria were only commonly cited in
      Germany, Spain and the UK as reasons for choosing the i.v. route at the beginning
      of the study. These were more commonly cited at the time of switch, although
      other criteria such as improved condition, were other significant reasons. The
      mean duration of i.v. treatment ranged from 4 days in the UK to 10 days in Italy,
      where most patients received the full course of treatment by the i.v. route.
      Unlike the other hospitals studied, the few patients in Italy who were switched
      to another form of treatment were as likely to receive intramuscular as oral
      administration (13% and 11%, respectively). CONCLUSIONS: The practice of and
      reasons for prescribing i.v. antibiotics varied in the hospitals studied.
      Objective clinical criteria were inconsistently cited as reasons for
      administering i.v. antibiotics and in general these reasons were unrelated to
      those given for the switch from i.v. to oral administration. In order for
      guidelines for switching from i.v. to oral antimicrobials to be routinely
      employed, explicit physiological criteria need to be recorded in a routine
      fashion. Closer co-operation between pharmacists and physicians may help in
      developing and implementing guidelines at a local level.

PMID- 12512159
TI  - Assessing occupational and environmental exposures that cause lung disease.
AB  - The approach to hazard identification and exposure characterization presented in
      this article will help physicians assess the likelihood that their patients with
      respiratory illness have relevant exposures in their work, home, or other
      environments. The clinician will identify potentially important exposures and
      s/he will develop an estimate of the level, duration, and frequency of exposure.
      With experience, such histories provide information critical to the recognition
      of occupational and environmental lung disease. Successful identification of such
      exposures provides an opportunity to halt, and even reverse, lung disease that
      can otherwise become chronic and progressive.

PMID- 12512160
TI  - Acute inhalation injury.
AB  - Recent events have underscored the importance of proper diagnosis and management
      of patients with inhalation injury. Clinicians who care for individuals who have
      sustained inhalation damage to their respiratory tract need to take a careful
      exposure history and be alert to possibilities of delayed effects and clinical
      deterioration. Although supportive care and prevention remain the cornerstone of
      current approaches to this condition, better understanding of the mechanisms of
      cellular injury and repair may lead to improved treatments in the future.

PMID- 12512161
TI  - Occupational upper airway disease.
AB  - The upper airway plays a critical role in filtering and conditioning air for the
      lungs. It provides the first line of warning and defense against microbials,
      allergens, and toxic inhalants. Current evidence suggests that the upper airway
      is susceptible to many of the pathogenic processes that the agents cause in the
      lower respiratory tract. Work-related rhinosinusitis or vocal cord dysfunction
      should prompt physicians and employers to identify the injurious agent(s) and
      formulate strategies to eliminate or reduce such exposures. Improving the work
      environment will prevent the development of new cases and the worsening of
      symptoms in existing cases.

PMID- 12512162
TI  - Occupational airways diseases from chronic low-level exposures to irritants.
AB  - Short-term, high-level exposures to dusts, gases, mists, fumes, and smoke that
      are irritating to the respiratory tract are capable of inducing asthma, the so
      called reactive airways dysfunction syndrome. Such exposures, however, do not
      occur frequently; chronic or recurrent exposures to lower levels of irritants are
      much more common. This article reviews the evidence that supports the concept
      that low-level exposures to respiratory tract irritants can contribute to the
      development of chronic obstructive pulmonary disease and asthma.

PMID- 12512163
TI  - Environmental tobacco smoke and adult asthma.
AB  - The long-term health consequences of ETS exposure have been established over the
      past two decades. Consistent epidemiologic evidence links ETS exposure with
      serious chronic health effects, including lung cancer and cardiovascular disease
      [1, 48, 49]. In this article, the evidence suggests a causal relationship between
      ETS exposure and new-onset asthma and asthma exacerbation among adults. Despite
      the growing knowledge of ETS-related health effects, smoking is still permitted
      in many public locations and workplaces [50, 51]. Because asthma is a visible
      condition among the general public, the evidence that links ETS exposure with
      adverse asthma health outcomes should provide policymakers with additional
      impetus for regulating public smoking and creating smoke-free public
      environments.

PMID- 12512164
TI  - Update on the health effects of outdoor air pollution.
AB  - The number of studies conducted on the health effects of air pollution has
      increased exponentially. Important methodological advances include the
      application of novel observational study designs, in particular the multi-city
      design, and the development and application of airborne particle concentrators
      for use in experimental human exposure studies and toxicological studies.
      Experimental data are validating and providing insight into some surprising
      observational findings.

PMID- 12512165
TI  - Pulmonary manifestations of intentionally released chemical and biological
      agents.
AB  - Recent events have underscored the importance of knowledge and understanding of
      biological and chemical agents that are intentionally released on civilian
      populations. Preparedness of the medical community to recognize and manage the
      resulting clinical syndromes will be a major determinant in the outcome of such
      attack, or a community's 'prognosis' for survival. The biological and chemical
      agents that have been weaponized produce diseases and toxidromes that are not
      commonly seen by clinicians in most parts of the United States. Patients or
      clusters of patients who present with febrile syndromes that are unusual for the
      geographic or seasonal setting should trigger notification of public health
      authorities and the use of state or national reference lab systems for augmented
      diagnostic support. In many cases, early, empiric therapy, administered before
      definitive diagnosis, is required for survival. The basic principles in the
      management of exposure to chemical agents include containment, prevention of
      secondary exposure, rapid decontamination, implementation of supportive and
      symptomatic care, and specific antidotes as indicated and available.

PMID- 12512166
TI  - Agricultural lung disease.
AB  - Agricultural work is associated with high rates of injury, disability, and
      illness. Agricultural workers are at increased risk for a variety of illnesses
      including respiratory disorders, dermatologic conditions, and cancer. The
      recognition of ODTS led to increased understanding of acute illness in farmers
      and grain workers. Previously, many cases of acute illness were probably
      erroneously called farmer's lung. The same agents that are responsible for ODTS
      are responsible for the high prevalence of bronchitis in certain agricultural
      workers. The recent description of the innate immune system is very exciting
      because it will lead to increased understanding of the pathogenesis of organic
      dust induced disorders.

PMID- 12512167
TI  - Update on respiratory disease from coal mine and silica dust.
AB  - Coal mine and silica dust cause significant respiratory disease in spite of
      modern dust control regulations. Susceptible individuals in exposed populations
      may develop fibrosing lung disease, obstructive airways disease, including
      chronic bronchitis and emphysema, or lung cancer. A careful occupational history
      that elicits exposure to respiratory hazards is the cornerstone of an accurate
      diagnosis. Treatment involves removal from exposure, supportive care, pulmonary
      rehabilitation, and when disabling disease is present, assistance obtaining
      compensation.

PMID- 12512168
TI  - Pulmonary impairment and disability.
AB  - Respiratory disorders, including occupational and environmental lung diseases,
      are prevalent. Physicians are frequently called upon to determine impairment and
      aid in the assessment of disability caused by these conditions, either as the
      treating physician or as an independent medical examiner. In this article we
      reviewed the role of physicians in determining the presence and severity of
      pulmonary disorders. A comprehensive clinical assessment and appropriate
      standardized tests, to objectively characterize the severity of impairment, are
      the key elements of the evaluation. This assessment may also include the
      physician's opinion regarding causative factors. Finally, disability
      determination is made by nonclinicians, through administrative means, based on
      the degree of impairment and a review of circumstances specific to the
      individual. Knowledge of these components of disability evaluation will help
      physicians to better serve their patients and supply appropriate data to the
      adjudicating system.

PMID- 12512169
TI  - An overview of United States law.
AB  - A broad array of legal concerns affects everyday practice in medicine. Through an
      understanding of the basic tenets of the law, providers may be able to better
      understand the risks, obligations, and rights associated with the law. Further,
      this understanding may assist them in more effective patient advocacy in their
      practices.

PMID- 12512170
TI  - Medical malpractice: a review of issues for providers.
AB  - The worlds of law and medicine meet in some very interesting and very important
      ways. Together, lawyers and physicians tackle such subjects as cloning, right to
      die, surrogate parenthood, and embryo preservation and implantation, to name a
      few. The most personal and painful nexus for physicians comes when a physician is
      sued and must then deal with the legal system as a defendant. The world of
      plaintiffs, experts, legal doctrines, state and federal law, and judicial
      application of law to the facts of the case can be intimidating. It is hoped that
      this overview has allowed the hematology-oncology practitioner to become more
      familiar with the theories and procedures involved in medical negligence actions.
      The physician, when comfortable with the basics, may better tolerate the apparent
      idiosyncrasies of the system and even may be able to protect him or herself from
      becoming involved in a lawsuit ab initio.

PMID- 12512171
TI  - Risk creation, loss of chance, and legal liability.
AB  - One can now only speculate as to the future of the law regarding risk creation
      and loss of chance. Freed from the moorings of the traditional rules in medical
      malpractice cases, courts are adopting a variety of approaches to this problem in
      a manner that approaches the idiosyncratic--the law is whatever it happens to be
      on any given day, in any given jurisdiction. Regrettably, until such time as
      uniform guiding principles are established, it appears that the laws governing
      the interaction between risk, causation, and liability will remain in a state of
      flux.

PMID- 12512172
TI  - Informed consent: issues for providers.
AB  - Although obtaining informed consent is an important part of the
      hematologist/oncologist's practice, understanding the legal consequences can
      assist the practitioner to understand why it is necessary to disclose as much
      information as he or she does. By following the standard of care used in the
      state of practice, the physician can decrease the risk of being sued by patients
      for lack of informed consent, thus fulfilling his or her legal and ethical duties
      by providing the patient with all the information necessary to make an informed
      decision.

PMID- 12512173
TI  - Advance directives and life-sustaining treatment: a legal primer.
AB  - Advanced directives are a natural extension of a patient's right to self
      determination of what actions will be taken upon his or her body. As such,
      instructional advanced directives such as living wills and DNR orders represent
      important patient preferences that must be adhered to in the health care context.
      In addition, health care proxies provide the patient with an authority for
      decision making in the event of incapacity. Overall, advanced directives provide
      health care providers, patients, and patient families with control over the kinds
      of care they do and do not desire at the end of life. Understanding the legal
      status of these instruments will provide the physician with another tool to
      advocate effectively for the patient.

PMID- 12512174
TI  - Definitions and implications of death.
AB  - Understanding the legal definition of whole-brain death is imperative for
      hematologists and oncologists who deal with end-of-life patients on a regular
      basis. At present, only whole-brain death in which there is no function of the
      upper brain or brain stem is legally recognized as legal death. Those advocating
      expansion of the current definition of death to encompass patients with higher
      brain death and brain-absent anencephalic infants cite increasing the organ pool
      and decreasing unnecessary treatment and costs as benefits. Those advocating a
      more narrow definition of death typically fear being misdiagnosed or prefer the
      traditional cardiopulmonary definition for personal and religious reasons. As
      medical technology advances, offering new hope to both the critically injured
      patients who might be potential donors and to those patients in need of donated
      organs, the definition of death will continue to be a topic of passionate debate.

PMID- 12512175
TI  - Alternatives to litigation for health care conflicts and claims: alternative
      dispute resolution in medicine.
AB  - Health care has undergone radical changes, and it may be predicted that further
      changes are in the offing as the burdens and the benefits of the newer
      configurations become known. Change in any system stresses it, creating
      opportunities for conflict as people and organizations adjust to new realities
      and encounter changed expectations. The opportunities for conflict in health care
      (and legal conflict with it), therefore, have been and will continue to be a
      measurable part of health care's daily life. Many of these conflicts can be
      managed through one or another of the several forms of ADR. Some ADR procedures
      are most productive when used as alternatives to impending litigation. Others may
      be employed when litigation is not likely but when the persistence of conflict,
      such as that within a newly structured provider organization, would otherwise
      take its toll on the productivity of the organization and those who work within
      it. The challenge in using ADR for any of these problems is similar to what
      physicians understand as differential diagnosis. A good therapy applied to the
      wrong case yields a bad result. The world of ADR has matured to the point at
      which the salient features of both cases and procedures are well-enough
      understood to allow for low-risk and high-benefit applications. This is
      particularly true for disputes involving allegations of medical error, where the
      indicators of efficacy are very positive and the risks to safety are comfortably
      low. Mediation in particular, but mediation of the interest-based style rather
      than the settlement conference style, deserves fuller consideration and broader
      use.

PMID- 12512176
TI  - Medical information, confidentiality, and privacy.
AB  - State laws and accreditation requirements dictate the form, ownership, and
      substance of medical records, as well as requirements for storage, access, and
      confidentiality. There are limited exceptions to these requirements but they are
      highly circumscribed. Federal law also outlines requirements to ensure the
      privacy of patient-identifiable information. Thus, providers must be aware of
      these rules both to protect patient information from being abused and to
      understand the affirmative obligations they have so as to avoid the significant
      penalties associated with breach of these provisions.

PMID- 12512177
TI  - Regulating hematology/oncology research involving human participants.
AB  - The conduct of hematology/oncology research, particularly clinical trials
      involving human participants, is an extensively regulated enterprise.
      Professionals in the specialty of hematology/oncology have important stakes in
      the success of biomedical research endeavors. Knowledge about and compliance
      strategies regarding the pertinent regulatory parameters are essential for
      avoiding negative legal repercussions for involved professionals. At the same
      time, there is a need to be aware of and actively resist the danger that strong
      [legal] protectionism might inadvertently result in undermining physician
      investigators' sense of personal moral responsibility in the conduct of human
      experiments. For all the limitations of that virtue in the protection of human
      subjects, it is surely not one that we would want medical scientists to be
      without [47]. Members of the potential participant pool, financial sponsors, and
      the general public must be convinced that everyone involved in the research
      enterprise is committed to operating within acceptable legal and ethical
      boundaries if the atmosphere of confidence and trust that is indispensable to the
      continued process and progress of investigation aimed at extending and improving
      quality of life for all of us in the future is to continue and flourish [48].

PMID- 12512178
TI  - Patient safety and health policy: a history and review.
AB  - Policy initiatives on many fronts have converged to improve patient safety. A
      major tension that characterizes this process is the attempt to achieve a balance
      between learning and control in complex systems with technical, social, and
      organizational components. Efforts to improve learning are marked by better
      information flow, discovery, flexibility in thinking, embracing of failures as
      learning opportunities, and core incentives to promote voluntary participation of
      all stakeholders in the process. Efforts to improve accountability are
      traditionally marked by public disclosure, meeting of certain widely disseminated
      standards, availability of performance measures, exposure to legal liability, and
      compliance with mandated directives (statutes, regulations, accreditation
      requirements). In some sense, these directions are mutually exclusive. Although a
      more collaborative regulatory-improvement model would be helpful in creating an
      industrywide safety culture, it is likely that learning and accountability
      functions will follow separate tracks. An exception would be policy that
      stimulates organizations to comply with regulation by showing how well and by
      what methods they are learning and how others can profit from these experiences.
      Any approach to improving patient safety should, at a minimum, include a
      nonpunitive in-depth mechanism for reporting incidents, postincident evaluations
      for identification of system changes to prevent subsequent occurrences, and state
      guaranteed legislative protection from discovery for all aspects of information
      gathered to improve patient safety. Nonpunitive approaches have yielded useful
      results in other industries [43]. State and federal courts, state licensing
      boards, and accrediting bodies such as JCAHO all function to maintain
      accountability and standards; however, the very fear of existing legal liability
      or its misapplication are the greatest hurdles to pioneering patient-safety
      efforts. The health care system needs to transform the existing culture of blame
      and punishment that suppresses information about errors and adverse events into a
      culture of safety that focuses on openness and information sharing to improve
      health care and prevent adverse outcomes. Education and leadership will be most
      important to creating and sustaining a strong safety culture and arguably the
      most important defense against preventable harms. Safety culture cannot be
      legislated, just as the old adage states that it is easier to pull rather than
      push a piece of spaghetti. Given the imbalances and inefficiencies of market
      forces in health care, perverse incentives that have strengthened resistance to
      change, and secrecy when it comes to adverse event information, however, it is
      likely that policy initiatives will continue to play an important role in the
      transformation of the industry to more highly reliable, safer levels of care.

PMID- 12512179
TI  - Pain management and liability issues.
AB  - Pain management is evolving as critics clamor for improvement in patient care.
      Progress, however, is surprisingly slow, the result of continued uncertainty by
      providers as to appropriate opioid use, fear of criminal prosecution, and lack of
      institutional attention to pain management. Progress, however, is also evident,
      with accreditors paying more attention to pain management, the implementation of
      team approaches in some hospitals, and the recognition by physicians and other
      providers that pain, just as any clinical problem, needs to be treated in an
      effective manner.

PMID- 12512180
TI  - E-health and e-medicine.
AB  - The world of e-health and e-medicine offer hematologists and oncologists
      wonderful opportunities to enhance and expand their practices and to offer
      patients the opportunity to gain access to information and specialty care never
      before available. Legal and political challenges abound, however, concerning the
      practice and financing of e-health and e-medicine. Financing and reimbursement
      for e-medicine are limited, licensure laws are structured in a way that inhibits
      telemedicine's widespread growth, public protection efforts are sluggish and
      spotty at best, and there are tremendous areas of uncertainty about such issues
      as malpractice exposure, patients' rights, and proper practices concerning
      physician-patient e-mail. It is impossible to predict what health care delivery
      will look like even a decade from now (and some would argue it would be a fool's
      errand to attempt to do so) [56]; however, despite all of these obstacles,
      physicians should continue to explore innovative ways to integrate computer
      technology and the Internet into medical practice.

PMID- 12512181
TI  - The rules of fraud and abuse.
AB  - It appears that the government is taking a no-holds-barred type approach to
      combating fraud and abuse of government programs by enacting new and by expanding
      existing statutes designed for this purpose. It is clear now, more than ever,
      that due to the abuse suffered by federal health care programs, the government,
      by and through its respective agencies, is using every resource available to
      track, identify, and prosecute those who defraud and attempt to defraud these
      programs. It is therefore imperative that hospitals and health care professionals
      take the necessary precautions to ensure that inadvertent violations of these
      statutes do not occur.

PMID- 12512182
TI  - Mucosal candidiasis.
AB  - This article examines the ecology and epidemiology of gastrointestinal
      candidiasis, esophageal candidiasis, chronic mucocutaneous candidiasis, urinary
      tract candidiasis, and vulvovaginal candidiasis. Such issues as pathogenesis and
      host defenses, clinical manifestations, diagnosis, and treatment are discussed.

PMID- 12512183
TI  - Deeply invasive candidiasis.
AB  - The incidence of invasive candidiasis is on the rise because of increasing
      numbers of immunocompromised hosts and more invasive medical technology. Recovery
      of Candida spp from several body sites in a critically ill or immunocompromised
      patient should raise the question of disseminated disease. Although
      identification to the species level and antifungal susceptibility testing should
      guide therapy, at this time amphotericin B preparations are the usual initial
      therapy for severe life-threatening disease. Azole therapy has an expanding body
      of evidence that proves it is as effective as and safer than amphotericin B
      therapy. Some forms of candidiasis (e.g., those with ocular, bone, or heart
      involvement) require a combined medical and surgical approach.

PMID- 12512184
TI  - Cryptococcosis.
AB  - Cryptococcus neoformans has risen to a worldwide highly recognizable major
      opportunistic pathogen with deadly consequences. It has become a model fungus to
      study a variety of paradigms in the host-fungus relationships. Genomic studies
      are advancing knowledge on its evolution and dissecting its virulence composite.
      Studies designed to understand host immunology to this fungus are leading to
      development of active and passive prevention and therapeutic strategies. This
      article collates and analyzes both new and old knowledge about the pathogen to
      help frame the meaning of human cryptococcosis as it starts to evolve in the new
      millennium.

PMID- 12512185
TI  - Aspergillosis. Pathogenesis, clinical manifestations, and therapy.
AB  - Diseases caused by Aspergillus species are increasing in importance, especially
      among immunocompromised hosts. Clinical manifestations are variable, ranging from
      allergic to invasive disease, largely depending on the status of the host's
      immune system. This article focuses on the pathogenesis and clinical
      manifestations of diseases caused by Aspergillus species, with more detailed
      discussion on therapy of the most morbid manifestation, invasive aspergillosis.

PMID- 12512186
TI  - Zygomycosis.
AB  - Zygomycosis, an uncommon but frequently fatal mycosis caused by fungi of the
      class Zygomycetes, develops most commonly as an opportunistic disease. Successful
      therapy involves a combined approach based on early diagnosis, prompt institution
      of medical therapy, and extensive surgical debridement of all devitalized tissue.
      Given the rarity of this condition, novel therapeutic strategies have been
      limited and only tested on an individual basis. The use of high-dose lipid
      formulations of amphotericin B, prompt reversal of the underlying predisposing
      condition, and hyperbaric oxygen are the most common strategies that have shown
      potential value in the treatment of zygomycosis.

PMID- 12512187
TI  - Emerging and less common fungal pathogens.
AB  - Less common and emerging fungal pathogens are often resistant to conventional
      antifungal therapy and may cause severe morbidity and mortality in
      immunocompromised hosts. Some Scedosporium species may be completely resistant to
      antifungal therapy. Hyaline septated filamentous fungi, such as Fusarium species,
      Acremonium species, Paecilomyces species, and Trichoderma species, are
      increasingly reported as causing invasive mycoses refractory to amphotericin B
      therapy. Dematiaceous septated filamentous fungi, such as Bipolaris species may
      cause pneumonia, sinusitis, and CNS infections that are unresponsive to current
      medical interventions. Trichosporon spp are resistant to the fungicidal effects
      of amphotericin B. An increasing number of different members of the class
      Zygomycetes are reported as causing lethal infections, despite aggressive medical
      and surgical interventions. Infections due to these and other less common and
      emergent fungal pathogens will likely continue to develop in the settings of
      selective anti-fungal pressure, permissive environmental conditions, and an
      expanding population of immunocompromised hosts.

PMID- 12512188
TI  - Fungal infections in nontransplant patients with hematologic malignancies.
AB  - Fungal infections are a major cause of morbidity and mortality in patients with
      hematologic malignancies. Candida and Aspergillus species are the most important
      opportunistic fungal pathogens in this patient population. Dimorphic fungi can
      cause serious infection in immunocompetent persons, but infection is more likely
      to be disseminated in patients with compromised cell-mediated immunity.
      Cryptococcus neoformans and Pneumosystis carinii typically cause infections in
      persons with severe T-cell suppression. The frequency of rare pathogenic fungi
      commonly resistant to amphotericin B has significantly increased over the past 20
      years among patients with hematologic malignancies. Examples of such emerging
      pathogens include Trichosporon, Fusarium, and Scedosporium species, and dark
      walled molds. This article reviews the epidemiology, clinical manifestations,
      diagnostic evaluation, and treatment of the major fungal pathogens in
      nontransplant patients with hematologic malignancies.

PMID- 12512189
TI  - [The PIPET or Patient Individual Plate Easy Test].
AB  - The fresh outbreak of allergies and especially that increasingly early for food
      or even for new pneumallergens (sensitization already in utero) pushes us to test
      increasingly various and many allergens in children. The insufficiency of
      compliance of certain children to allergic skin tests encouraged us to seek new
      diagnostic methods. In our office we developed a new method of diagnosis by
      multipuncture, individualized and easily adaptable to each child. It is about a
      fast and reproductible prick-test which avoids stains and smudges due to the
      application of drops directly on the skin. It makes it possible to initially
      place easily all the tests on a plate (PIPET or Patient Individual Plate Easy
      Test) then on the skin by a multipuncture method. The tests can even already be
      prepared in the days which precede, provided that the plates are put in the
      fridge, with the name of the patient and the allergens used, for memory. It is
      about a rigorous test, reliable and careful, easy to carry out even in the most
      difficult children.

PMID- 12512190
TI  - Candida and allergy.
AB  - The role of Candida species in allergic diseases is briefly reviewed pointing out
      the more common forms of cutaneous and respiratory allergy where Candida can be
      implied, the current laboratory diagnostic methods and the possible effectiveness
      of Candida immunotherapy in selected patients.

PMID- 12512191
TI  - Optimal management of atopic dermatitis in infancy.
AB  - The necessity to optimise the management of atopic dermatitis of infants needs
      knowledge of three components: increase of prevalence, extreme frequency of food
      allergy and increase in the frequency of the syndrome of multiple allergies, that
      frequently develops into asthmatic disease. Management of DA in infancy (first
      year of life) is based on the global strategy of understanding the physiological
      Th2 polarisation at birth, that does not allow a re-equilibration of the Th1-Th2
      balance that progresses in the first six months of life (in normal infants)
      making in this period a window of opportunity for sensitizations. Prevention in
      high-risk children (familial history of atopy) covers the non-exposure to in door
      pollutants (tobacco and volatile organic compounds), breast-feeding or a
      hypoallergenic formula for a hydrolysate of pork and soya proteins or better an
      extensive hydrolysate of casein. Four situations require moving to an amino acid
      substitute: failure to thrive, severe atopic dermatitis, a syndrome of multiple
      food allergies, allergy to hydrolysates. Reintroduction of foods should be
      considered with the least delay so as to induce digestive tolerance. It should
      take into account the clinical development, the intensity of the sensitisation
      and eventually depend on a realistic test of introduction. Management of DA
      searches for recovery of generalized eczema, failure to immediate improvement of
      quality of life prevention of immediate complications (local sepsis) acceleration
      of return to food tolerance. Prevention of ulterior development of asthma by
      immediately introducing measures to diminish respiratory exposure to allergens
      and tobacco is hoped for.

PMID- 12512192
TI  - [Systemic urticaria induced by hops].
AB  - The authors report a patient who presented 4 times a systemic urticaria with
      arthralgias and fever treated by corticosteroids with efficacy. Wild hop (Humulus
      lupulus) was finally proved to be the causal factor. H.L. belongs to the
      cannabinaceas family. Hop dermatitis in hop workers population is the main widely
      described clinical manifestation. Rhinitis, conjunctivitis, asthma are rare as
      soon as contact urticaria. IgE-anti Hop induced allergies are described in the
      literature. However, in some cases of reactions to hop the mechanisms are
      uncertain: toxicity--possible role of lupuline--or immunoallergic processus with
      immunocomplexes (IC) (with increased IC in serum) and systemic urticaria such as
      in our observation.

PMID- 12512193
TI  - [Inhaled corticoids and systemic secondary effects: controversies].
AB  - Studies that compare the systemic impact of inhaled corticosteroids (CI) abound
      in the literature often with contradictory results. Most of the studies report
      secondary biological effects in the suprarenal function without clinical effect
      due to taking high doses of inhaled corticosteroids. Surveillance of the
      secondary effects on bone is difficult to demonstrate. Finally, speed for
      recognition in asthmatic children during the first year of treatment is slowed
      down but the level at adult age is not affected. The variability of these results
      is associated with the former taking of corticosteroids by the general route.
      Administration of corticosteroids by the systemic route, therefore makes
      difficult the evaluation of secondary effects due only taking inhaled
      corticosteroids.

PMID- 12512194
TI  - The controversy over breast cancer screening.

PMID- 12512195
TI  - Development of a database of clinical guidelines.

PMID- 12512196
TI  - Managing side effects of radiotherapy in head and neck cancer.
AB  - Curative radiotherapy for head and neck cancer causes very significant side
      effects. In addition to their considerable impact on the patient's quality of
      life, these effects can prejudice treatment outcome. This review looks at the
      management of the adverse effects of radiotherapy for head and neck cancer.

PMID- 12512197
TI  - Penile cancer: an overview.
AB  - Carcinoma of the penis affects 1 in 100,000 men per year in most developed
      countries. It accounts for less than 1% of adult malignancies in Europe and the
      USA. Survival is excellent if diagnosed early, but most men present up to 1 year
      after the initial lesion is noted. Unfortunately the treatment of metastatic
      disease is still disappointing.

PMID- 12512198
TI  - Management of skeletal metastases.
AB  - Bone is a frequent site of tumour metastasis and is the third most common site of
      metastatic carcinoma. With advances in the use of immunotherapy, hormonal
      manipulation, chemotherapy and radiation for the palliation of patients with
      metastatic bone disease, significant improvements in survival, wellbeing and
      overall quality of life have been achieved.

PMID- 12512199
TI  - The abdominal radiograph: a pictorial review.
AB  - The plain abdominal radiograph is one of the most frequently requested X-ray
      examinations by junior surgical and accident and emergency staff. Interpretation
      is often difficult, but this review outlines normal appearances, suggests a
      strategy for evaluation, and covers the common pathological appearances seen in
      hospital practice.

PMID- 12512200
TI  - Smart handles and red flags in neurological diagnosis.
AB  - Eliciting a full history and undertaking a complete neurological examination is
      time consuming. Knowledge of diagnostic short cuts (smart handles) and caveats
      (red flags) can speed up this process but care is needed as many tips given here
      have not been validated scientifically.

PMID- 12512201
TI  - Noonan syndrome: a brief overview.
AB  - Noonan syndrome is a relatively common dysmorphic syndrome. The typical features
      include short stature, cardiovascular abnormalities and a characteristic facies.
      Children with Noonan syndrome have a considerable number of potential health
      problems, which are highlighted in this article. However, most individuals with
      this condition live a normal life.

PMID- 12512202
TI  - Formal, structured teaching in postgraduate training: a learner-centred
      educational programme.
AB  - Medical education focuses on a learner-centred approach, but postgraduate
      training programmes have struggled to embrace this practice. In the West Midlands
      Deanery, a 2-year rolling postgraduate educational programme in obstetrics and
      gynaecology has been developed to equip trainees with the knowledge, skills and
      attitudes necessary to promote self-directed learning, via independent learning,
      interactive large-group presentations and small-group, peer-led activities.

PMID- 12512203
TI  - Pelvic fractures.

PMID- 12512204
TI  - Amiodarone-induced thyrotoxicosis.

PMID- 12512205
TI  - Lowering lipids in eye disease.

PMID- 12512206
TI  - An endocrine potpourri.

PMID- 12512207
TI  - A right atrial mass: thrombus, tumour or other?

PMID- 12512208
TI  - Foxglove poisoning.

PMID- 12512209
TI  - Should we use inhaled nitric oxide in acute respiratory distress syndrome?

PMID- 12512210
TI  - Sex differences and analgesics.

PMID- 12512211
TI  - Epidemiology of analgesic use: a gender perspective.
AB  - BACKGROUND AND OBJECTIVE: Women consistently report significantly more frequent
      analgesic use in epidemiological studies. The aim of this study was to analyse
      the influence of medical and non-medical factors on the difference in use of
      analgesics between women and men from a population perspective. METHODS: Cross
      sectional survey. Postal questionnaires were sent to a random sample of the
      general population in the country of Uppland, Sweden (5404 answered the
      questionnaire, response rate: 68%). RESULTS: 34.8% of the women and 21.4% of the
      men had used analgesics during the two week recall period (Odds Ratio = 1.96).
      Social structure, social status, marital status, educational level, economic
      situation, lifestyle, attitudes toward drugs, medication knowledge and self-care
      orientation were of minor importance for the difference in use between women and
      men. Difference in prevalence of various types of pain and ache and the degree of
      pain experienced were the most influential factors affecting the difference in
      use. However, when all factors were analysed there remained a substantial
      difference in use between women and men (OR = 1.39, CI (95%) 1.20 to 1.60).
      CONCLUSIONS: In the population, women use analgesics much more frequently than
      men. Consequently women may be at greater risk for adverse effects and
      dependency. Some of the gender difference is explained by the greater frequency
      of pain conditions among women, but a significant difference in use still remains
      to be explained.

PMID- 12512213
TI  - Failure mode and effects analysis in health care.

PMID- 12512212
TI  - Sex differences in analgesic responses: evidence from experimental pain models.
AB  - BACKGROUND AND OBJECTIVE: Sex-related influences on the experience of pain have
      received considerable empirical attention. Women are at greater risk for several
      forms of clinical pain and exhibit greater perceptual responses to experimental
      pain. In recent years, investigators have turned their attention to the influence
      of sex-related factors on analgesic responses. The purpose of this review is to
      examine the literature on sex differences in analgesic responses, emphasizing
      findings from experimental studies. METHODS: First, important methodological
      issues in laboratory pain research are presented, and sex differences in
      responses to experimentally-induced pain are briefly addressed. Next, previous
      data from non-human animal research and human experimental and clinical research
      related to sex differences in analgesia are discussed. Also, preliminary results
      are presented from an ongoing study in our laboratory examining analgesic
      responses in women and men. RESULTS AND CONCLUSIONS: Both previous research and
      preliminary findings from our laboratory suggests that opioids produce greater
      analgesic responses in women than men. Potential mechanisms underlying sex
      differences in analgesia are proposed, and important directions for future
      research are suggested.

PMID- 12512214
TI  - Implementation approach approved for long-term care accreditation option.

PMID- 12512215
TI  - Bed rail-related entrapment deaths.

PMID- 12512216
TI  - Penny dreadfuls.

PMID- 12512217
TI  - Long-term care. No grey areas.
AB  - The government policy on the future of long-term care is unclear. The debate has
      been narrowly focused on home closures and users' interests have been
      marginalised. The government's U-turn on care standards in July sent out worrying
      messages about whose interests are being protected. The NHS may have a role in
      providing capital investment for new developments. Experience in Scandinavia
      suggests more intense home support could lessen reliance on residential services.

PMID- 12512218
TI  - Long-term care. Unknown quantities.
AB  - A small study of nursing home owners, managers, residents and relatives found
      effective management depended on strong leadership skills, high bed occupancy,
      enthusiastic staff and low staff turnover. Funding problems were a key issue for
      homes, creating massive insecurity for residents, relatives and staff. There was
      a feeling that nursing homes could be used more effectively by the NHS, but there
      were concerns about capacity and competence. The viability of homes would be
      improved by annual block booking by the NHS. This would also facilitate the
      development of intermediate care. A national development programme for nursing
      home managers is needed.

PMID- 12512219
TI  - Can 401(k) accumulations generate significant income for future retirees?
AB  - This Issue Brief develops a model that project the proportion of an individual's
      preretirement income that might be replaced by 401(k) plan accumulations at
      retirement, under several different projected scenarios. The 401(k) participant
      behaviors in the model are based on the year-end 2000 database collected by the
      Employee Benefit Research Institute (EBRI) and the Investment Company Institute
      (ICI) in their collaborative effort known as the EBRI/ICI Participant-Directed
      Retirement Plan Data Collection Project. The most significant factor affecting
      projected replacement rates at retirement is having access to a 401(k) plan.
      Projected replacement rates from 401(k) accumulations at retirement are reduced
      significantly when participants are not offered a 401(k) plan in all portions of
      their careers. Most 401(k) participants tend to have contributions in any given
      year. Thus, projecting that participants always have contributions (their own
      and/or employer contributions) every year raises projected replacement rates, but
      not by much compared with the importance of being offered a plan to begin with.
      The model simulations show that participant activities such as taking loans,
      taking preretirement withdrawals, or cashing out account balances at job change
      reduce projected 401(k) accumulations and thus replacement rates at age 65.
      Because loans are forecast to be paid back to the account in full, their effect
      on replacement rates at retirement in the model is the smallest. Even if equity
      returns in the future are projected to replicate the worst 50-year segment in the
      Standard & Poor's (S&P) 500 history (1929 to 1978), 401(k) accumulations are
      still projected to replace significant proportions of projected preretirement
      income. Another projection scenario forecasts participants experiencing a
      simulated three-year bear market (negative equity returns) either early in their
      careers, near the middle of their careers, or at the end of their careers.
      Forecasts of the effects of bear markets on 401(k) balances show that a bear
      market in equities is projected to have the largest effect the closer it occurs
      to age 65 (retirement), even though older participants typically have diversified
      their portfolios away from equities. A three-year bear market for those early in
      their careers would reduce median replacement rates from 401(k) accumulations by
      an estimated 2.9-3.7 percentage points, compared with 13.4-17.7 percentage points
      for those immediately before retirement. Similarly, a simulated three-year bull
      market (positive equity returns) is projected to have a larger positive effect on
      projected account balances and replacement rates the closer it occurs to
      retirement.

PMID- 12512220
TI  - Happy birthday MPH (Master of Public Health): it's time for the party--a reality
      check and a cure.

PMID- 12512221
TI  - Origins and early development of the case-control study: Part 1, Early evolution.
AB  - This paper traces the origins and early development of the case-control study,
      focusing on its evolution in the 19th and early 20th century. As with other forms
      of clinical investigation, the case-control study emerged from practices that
      originally belonged to the realm of patient care. This form of disease
      investigation can be viewed as the knitting together of medical concepts
      (caseness, disease etiology, and a focus on the individual)--and medical
      procedures (anamnesis, grouping of cases into series; and comparisons of the
      diseased and the healthy)--that are of ancient origin, but which were seldom
      brought together until the 20th century. The analytic form of the case-control
      study can be found in 19th century medical literature, but did not appear to be
      viewed as a special or distinct methodology. A number of clinical investigations,
      and several sociological studies, in the first half of this century can be
      described as case-control studies, the most fully developed of which was Janet
      Lane-Claypon's 1926 study of breast cancer.

PMID- 12512222
TI  - Repeated self-reported injuries and substance use among young adolescents: the
      case of Switzerland.
AB  - OBJECTIVES: The prevalence of repeated self-reported injuries among adolescents
      between 12 and 15 years of age and the association with the use of alcohol,
      drugs, and intense sporting activity are described. METHODS: A Swiss national
      representative sample of 7196 adolescents completed a questionnaire in 1998. They
      were asked about their use of alcohol and drugs and whether they had suffered
      injuries requiring medical attention in the preceding 12 months. "Repeated
      injuries" were defined as three or more reported injuries. RESULTS: 46.8% males
      and 43.8% females reported one or more injury in the previous 12 months. Ten
      percent of the males and 8.6% of the females reported repeated injuries. Regular
      use of alcohol (odds ratio (OR): 1.55, confidence interval (CI): 1.23-1.96),
      drunkenness (OR: 1.73, CI: 1.34-2.22) use of illegal drugs (for 14 and 15 year
      olds, OR: 1.84, CI: 1.05-3.23) and intense sporting activity (OR: 1.59, CI: 1.31
      1.93) were risk factors for repeated injuries whilst gender was not (OR: 0.99,
      CI: 0.81-1.20). CONCLUSIONS: The occurrence of repeated injuries is frequent
      among adolescents, and is associated with use of alcohol, illegal drugs, and
      intense sporting activity.

PMID- 12512223
TI  - Brief scales for measurement of functional social support and psychological
      resources in French-speaking adults.
AB  - OBJECTIVES: Psychological resources and social support are important determinants
      of health, but brief and validated scales measuring these dimensions in French
      are lacking. METHODS: Instruments measuring self-esteem and mastery, and
      affective and confident social support were administered by mail to 1257
      university students. Factor analysis, internal consistency statistics, and
      correlations with related variables were used to derive abbreviated scales and
      confirm their validity. RESULTS: Factor analysis and item reduction yielded four
      brief scales: mastery (4 items), self-esteem (4 items), affective social support
      (2 items), and problem-solving social support (4 items). All four scales had few
      missing items and adequate internal consistency (Cronbach's alpha > 0.70). All
      scores were associated with self-reported general health, and with visits to
      mental health specialists. Scores of self-esteem and mastery were also associated
      with physician visits (inversely), and confidence in finishing studies and
      finding a job. Scores of affective and confident social support correlated with
      the intensity of social activities and the number of people the respondent could
      count on. CONCLUSIONS: The abbreviated scales retained adequate psychometric
      properties and may be usefully applied in health research among similar French
      speaking populations.

PMID- 12512224
TI  - [The use of medical services and the utilization rate in screening programs in
      relation to social class: results of a representative survey in Bavaria].
AB  - OBJECTIVES: This article aims to analyse utilisation of medical services and
      screening programmes in relation to social class. METHODS: 2051 adults in Bavaria
      were interviewed using computer-assisted telephone interview (CATI) in 1999/2000.
      Social class was established from the income-adjusted Winkler social category
      index. Data were standardised by age and sex. If social class differences were
      found, separate analyses for education and income effects were conducted.
      RESULTS: Higher education was found to be associated with visits to specialist
      and vaccinations. The purchase of over-the-counter medication was related to
      higher education and family income. Frequency of HIV-tests was higher in higher
      social classes but not related to higher education or better financial situation.
      Utilisation rates for screening programmes for various types of cancer were
      similar in all social classes. CONCLUSIONS: The results show that social class
      differences in health behaviour in Bavaria prevail. Positive health behaviour is
      often associated with higher education. Compared to earlier findings social class
      effects on the utilisation of cancer screening appears less pronounced.
      Preventive measures seem to have reached all social classes to a similar degree.

PMID- 12512225
TI  - [Behavior of sunbed users in Switzerland].
AB  - OBJECTIVES: A constant rise in the number of skin cancer cases has been observed
      during the last few years. An important reason for this trend is that exposure of
      the population to UV radiation is higher. Although natural UV radiation is the
      major source, exposure due to use of sunbeds must be considered from the point of
      view of prevention. METHODS: 151 sunbed users in Bern and Basel were questioned
      on their reasons for visiting a solarium, their behaviour when using a sunbed and
      their awareness of risks resulting from UV radiation. RESULTS: It was shown that
      young women are the most frequent sunbed users. Also, sunbeds are often used
      regularly, not only for cosmetic reasons but also from a desire for relaxing and
      well-being in the warmth and light. Although most of the persons questioned were
      aware of certain health risks resulting from UV radiation, this knowledge hardly
      influenced their behaviour. Thus, more than half the people questioned use
      sunbeds longer and more often than advised by international recommendations.
      CONCLUSIONS: In view of a continuing increase in the number of skin cancer cases
      the improvement of preventive strategies for sunbed users is of major importance.
      Another urgent requirement is informing the public and increasing the general
      awareness of possible adverse health effects caused by UV radiation.

PMID- 12512226
TI  - [Prevalence of dementia in the City of Zurich].
AB  - OBJECTIVES: The purpose of the study was to estimate the prevalence rate of
      dementia (PRD) in relation to age, gender, and ApoE-genotype. METHODS: The random
      sample consisted of 465 subjects aged 65 and more. The interview was conducted by
      means of the Canberra Interview for the Elderly. The genotyping of ApoE has been
      performed by a combination of the polymerase chain reaction and a gel
      electrophoresis separation. RESULTS: The overall PRD amounted to 10.1% (95% CI
      6.8-13.3%) and was higher among females (12.2%) than among males (4.9%). The
      gender difference was of borderline statistical significance (OR 2.17; 95% CI
      0.97-4.84 adjusted for age, education level). PRD rose significantly with age. In
      contrast, the possession of one copy of ApoE-epsilon 4-allele was not associated
      with a higher risk of having dementia (OR 1.48; 95% CI 0.60-3.63 adjusted for
      age, gender, education level). CONCLUSIONS: These results are consistent with the
      finding from other authors.

PMID- 12512227
TI  - Changes in anthropometric measures in men and women across the life-span:
      findings from the InCHIANTI study.
AB  - OBJECTIVES: To describe the age distribution of anthropometric parameters in a
      population-based sample of older persons. METHODS: Cross-sectional survey of a
      population-based sample of persons over a wide age-range living in the Chianti
      area, Italy, between 1998 to 2000. Total cohort: 1453 men and women, of whom 424
      younger than 65 and 1029 aged 65 years or older. Participation rate: 69.4% in <
      65 yrs and 91.6% in > or = 65 yrs. Analytical cohort: anthropometric measures
      were available for 1266 subjects. RESULTS: Height and weight declined with
      increasing age in both sexes. In men, Body mass index (BMI) increased with age up
      to age 45-54 and then it declined. In women, it reached its maximum at age 65-74
      and remained higher than in men in each corresponding age group above 65 years of
      age. Waist-to-hip ratio (WHR) progressively increased in men up to age 55-64 and
      then slightly declined. In women WHR steadily increased over the entire age
      range. CONCLUSIONS: Height and weight decline with age, regardless to differences
      in body size attributable to secular trend. In both sexes, important fat
      redistribution occurs between 45 and 54 years and in older women the increase in
      WHR mostly reflects a reduction of fat deposits in the hips. This information may
      be relevant for a correct interpretation of changes in WHR in older persons.
      However, these findings were obtained in a cross-sectional study and should be
      verified in a longitudinal perspective.

PMID- 12512228
TI  - Key steps in planning a survey.

PMID- 12512229
TI  - Oral eicosapentaenoic acid for acute colonic graft-versus-host disease after bone
      marrow transplantation.
AB  - We investigated whether pretreatment with eicosapentaenoic acid, an inhibitor of
      leukotriene (LT) B4, could ameliorate acute colonic graft-versus-host disease
      (GVHD) after bone marrow transplantation (BMT). Seventeen patients undergoing
      unrelated BMT were divided into two groups, with eight patients receiving
      eicosapentaenoic acid and nine not receiving it. The grade of GVHD after
      transplantation was compared with that estimated from the pretransplantation LTB4
      level. The levels of LTB4 and several cytokines were also monitored. The actual
      grade of GVHD was lower than that estimated from LTB4 levels in three of the
      eight patients from the treated group, and there was a significant difference
      between the treated and untreated groups (p < 0.05, chi 2 test). The levels of
      LTB4, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma)
      were all significantly lower in the treated group (p < 0.05, Student's t-test).
      These findings suggest that eicosapentaenoic acid may ameliorate acute colonic
      GVHD when administered from before BMT.

PMID- 12512230
TI  - Calcium dobesilate ameliorates lung injury following lower limb
      ischemia/reperfusion.
AB  - We examined the effects of calcium dobesilate on ameliorating the lung damage
      following ischemia-reperfusion injury in skeletal muscle of rats. A well known
      antioxidant, dimethyl sulfoxide, was also tested for comparison. The study
      included three groups: normal saline, dimethyl sulfoxide and calcium dobesilate.
      Plasma bicarbonate, creatine kinase, lactate dehydrogenase, thiobarbituric acid
      reactive substances (TBARS), as well as muscle and lung tissue TBARS levels were
      measured. Lung tissue samples were taken for histological examination. The
      dimethyl sulfoxide group showed significant amelioration of plasma (p = 0.004),
      skeletal muscle (p = 0.006) and lung TBARS (p = 0.004) levels, compared with
      controls. Calcium dobesilate-treated rats showed significantly low level muscle
      (p = 0.025) and lung TBARS (p = 0.004), compared with the control group. The
      extent of lung injury according to the histological findings was less in the
      dimethyl sulfoxide (p = 0.004) and calcium dobesilate (p = 0.003) groups. These
      observations indicated that calcium dobesilate acted effectively in the
      prevention of lung damage following ischemia-reperfusion injury in the rat
      skeletal muscle.

PMID- 12512231
TI  - Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils.
AB  - The effects of zafirlukast, a cysteinyl-leukotriene receptor antagonist, on the
      generation of the reactive oxygen species (ROS) released during respiratory
      bursts of human polymorphonuclear neutrophils (PMNs) is still unknown. The aim of
      this study was to investigate the ability of zafirlukast to interfere with the
      respiratory burst of PMNs. Respiratory burst responses of PMNs were investigated
      by luminol-amplified chemiluminescence (LACL) using particulate (Candida albicans
      and zymosan) and soluble stimulants [N-formyl-methionylleucyl-phenylalanine
      (fMLP) and phorbol 12 myristate 13 acetate (PMA)]. When incubated with PMNs for
      10 min at concentrations ranging from 5 x 10(-9) M to 5 x 10(-6) M, zafirlukast
      did not significantly affect the respiratory bursts of PMNs induced by either the
      particulate or soluble stimuli. However, after incubation for 60 min, it did
      reduce the respiratory bursts of PMNs in a concentration-related fashion when the
      PMNs were stimulated with fMLP, and at a concentration of 5 x 10(-6) M when the
      stimulus was PMA. No significant effects were seen when the PMNs were challenged
      with particulate stimuli. Zafirlukast is able to interfere with the activation of
      the PMNs respiratory burst induced by soluble stimulants. The different behavior
      determined by different times of contact and different stimuli opens the way to
      interpretations concerning the antioxidant effect of zafirlukast.

PMID- 12512232
TI  - The SH-metabolite I of erdosteine, a mucolytic drug, enhances the inhibitory
      effect of salbutamol on the respiratory burst of neutrophils.
AB  - Reactive oxygen species (ROS) are a common denominator of airway inflammation
      associated with chronic obstructive pulmonary disease (COPD) and asthma, as well
      as with less frequent lung diseases such as idiopathic pulmonary fibrosis (IPF),
      acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF). The most
      frequently administered drugs used to treat these diseases are bronchodilators,
      antioxidant/antiphlogistic agents and mucoactive drugs. The metabolization of the
      mucoactive drug erdosteine produces an active metabolite (Met I) with a reducing
      SH group. In addition to its mucolytic action, Met I also has useful antioxidant
      activity. The various activities of beta 2-agonists include their ability to
      reduce the respiratory burst of neutrophils and the subsequent release of ROS.
      beta 2-Agonists and mucoactive drugs may be administered to the same patients
      during the treatment of lung diseases. The aim of this study was to investigate
      the ability of Met I to potentiate the activity of salbutamol in inhibiting the
      in vitro respiratory burst of neutrophils by means of chemiluminescence. The
      combination of Met I 5 and 10 micrograms/ml with salbutamol 10(-5), 10(-6) and
      10(-7) M led to a significant reduction in respiratory bursts when the
      neutrophils were stimulated with the soluble stimulant N-formyl-methionylleucyl
      phenylalanine (fMLP). The combinations of the two drugs that reduced the
      respiratory bursts when a particulate stimulus (Candida albicans) was used were
      those containing 10(-5) M of salbutamol. The reasons for this different behavior
      remain unclear and raise questions about the specific roles, sites and mechanisms
      of action of the different types of stimulation undergone by the respiratory
      airways.

PMID- 12512233
TI  - Can losartan improve cardiac performance during the treadmill exercise test in
      hypertensive subjects?
AB  - Systolic blood pressure (SBP) normally increases during exercise. This increase
      is frequently exaggerated in hypertensive individuals. The aim of our study was
      to evaluate the antihypertensive effects of losartan at peak exercise and on
      cardiac performance during the treadmill test in individuals with essential
      hypertension. Forty subjects with a mean age of 44.2 +/- 12.4 years and with mild
      to-moderate essential hypertension were enrolled. After a 14-day washout period,
      all selected subjects were given a treadmill exercise test using the modified
      Bruce protocol for exercise. The test was performed at the end of the washout
      period (step 0), again after 1 month (step 1), after 3 months (step 2) and after
      6 months (step 3) of losartan administration (50 mg/daily per oral). Heart rate,
      SBP and diastolic blood pressure (DBP) were measured at rest and at maximal
      exercise. Exercise duration and double product were also recorded. In all
      patients who completed the study, a significant reduction from baseline in SBP at
      rest was found at 3 and 6 months (p < 0.05). No significant reduction from
      baseline in SBP at peak exercise was observed. No significant changes from
      baseline were found in double product, DBP, heart rate or exercise time. The
      results of our study suggest that losartan is effective in reducing blood
      pressure only at rest but is unable to improve exercise BP response or cardiac
      performance in subjects with mild-to-moderate essential hypertension.

PMID- 12512234
TI  - Fluconazole in the treatment of pediatric tinea capitis caused by Microsporum
      canis.
AB  - Fluconazole has been shown to be effective in the treatment of fungal scalp
      infections in children; however, there is limited experience of its use in
      Microsporum scalp infections. We studied 11 children with tinea capitis caused by
      Microsporum canis who received oral fluconazole at a dose of 5-7.5 mg/kg/day for
      6 weeks. Mycological cure was observed in two of the 11 patients at week 4 from
      the start of therapy, in four patients at week 8 and in three patients at week
      16. One of the remaining patients had positive mycology at week 8, but was
      unavailable for further evaluation. Fluconazole was effective in treating
      pediatric tinea capitis caused by Microsporum canis and was well tolerated.
      Clinical and mycological response was achieved in some patients weeks after the
      cessation of the administration of fluconazole.

PMID- 12512235
TI  - Various Streptococcus species isolated from infectious skin diseases.
AB  - An evaluation was carried out of the types of Streptococcus spp. (excluding
      Streptococcus pyogenes) isolated from infectious skin diseases, and their
      susceptibilities to eight antimicrobial drugs of the Streptococcus spp. isolated.
      The types of diseases were also evaluated. A total of 29 Streptococcus spp. were
      identified and Streptococcus agalactiae was the most common. Streptococcus spp.
      were found to be susceptible to the eight antimicrobials used except gentamicin;
      susceptibility to gentamicin varied according to species. Susceptibility to beta
      lactams was 100% and this drug should be considered the antimicrobial of choice
      in Streptococcus spp. treatment.

PMID- 12512236
TI  - Risk management in therapeutics: when the patient becomes the last line of
      defense.

PMID- 12512237
TI  - Drug safety withdrawals: who is responsible for notifying patients?

PMID- 12512238
TI  - High rates of adverse effects and patient unawareness of withdrawn lipid-lowering
      drug combination in a public hospital clinic.
AB  - PURPOSE: Examine use, patient awareness and outcomes of concurrent cerivastatin
      and gemfibrozil in a public hospital clinic system 2 weeks following cerivastatin
      withdrawal. METHODS: Electronic pharmacy records for cerivastatin prescriptions
      for 1 year preceding withdrawal were downloaded and linked to gemfibrozil
      prescriptions. Patients with concurrent prescriptions were surveyed for current
      use, awareness of withdrawal/warnings, adverse effects and creatine phosphokinase
      (CK) results. RESULTS: From August 2000 to August 2001, 29,377 prescriptions for
      cerivastatin were dispensed for 10,780 unique patients; 211 (2%) also received
      gemfibrozil. Prescription time frames for the two drugs overlapped for 67
      patients. Interview of 47 patients revealed 35 actually taking both. 18/35
      (51.4%) were still taking both drugs 2 weeks after market-withdrawal of
      cerivastatin. Only 7/46 (21.2%) had 'heard the news' about withdrawal. 19/46
      (41.3%) described muscle-related symptoms; nine reported severe symptoms. Only 13
      (28.3%) had CK monitoring. 5/8 symptomatic patients monitored had CK values > 200
      U/L. (> 1000 U/L in two cases.) CONCLUSIONS: Despite escalating labeled warnings,
      nearly 2% of patients prescribed cerivastatin received gemfibrozil prescriptions,
      1/3 concurrently. Most were still taking this combination 2 weeks after
      cerivastatin withdrawal and unaware of publicized warnings. Nearly half
      experienced muscle-related symptoms. More reliable methods for preventing
      prescription/dispensing of interacting medications and alerting patients about
      drug recalls are warranted.

PMID- 12512239
TI  - Spontaneous reporting of adverse drug reactions by nurses.
AB  - BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) remains one of
      the most effective methods to detect new and serious drug reactions. However, it
      is well known that there is a high degree of under-reporting. OBJECTIVE: This
      study was carried out as an attempt to improve and increase the reporting of ADRs
      by investigating the utility of nurses reporting in addition to physicians, as
      usual. METHODS: During a 12-month study period, nurses working at two departments
      of geriatric medicine in northern Sweden received special instruction regarding
      drugs and ADRs, ADR reporting and special aspects of ADRs in elderly people. The
      reports from the nurses were scrutinized concerning the seriousness of the
      reaction, reported drugs and type of reaction (type A or B). All nurses working
      at the two departments (117) were eligible to report but in practice only those
      attending the teaching sessions did so. A comparison with historical reporting
      and with reporting from other geriatric departments in Sweden was also carried
      out. At the end of the study all participating nurses received a questionnaire
      aimed at investigating their attitudes towards ADR reporting. RESULTS: After the
      12-month study period 18 ADR reports involving 22 reactions had been received.
      Seven of these were assessed as serious reactions. All of the reactions were of
      type A. In comparison, during the corresponding time period from the study
      clinics during the preceding year, only two reports were registered. During the
      study period only 15 reports were registered from the other 50 geriatric
      departments in Sweden. CONCLUSION: Even though the total number of ADR reports
      was small, our data indicate a substantial increase in the reporting rate. This
      indicates that instructed and interested nurses could play an important role in
      detecting and reporting suspected ADRs.

PMID- 12512240
TI  - Pharmacoepidemiologic implications of erroneous varicella vaccinations in
      pregnancy through confusion with Varicella zoster immune globulin.
AB  - A series of case reports to the varicella vaccine Pregnancy Registry described
      inadvertent administrations during pregnancy of this live virus product instead
      of the intended Varicella zoster immune globulin. Cases continued to accrue
      despite an early publication about the pattern. The persistent problem warrants
      specific educational efforts to prevent further repetitions. It also has more
      general implications for medical product safety surveillance. First, this
      problem's original detection depended on the Pregnancy Registry's open-ended
      collection of information about pregnancy exposures. It could have escaped
      recognition through surveillance limited to pre specified potential risks. This
      need for unrestricted reporting and human vigilance to sift through case stories
      has particular relevance for efforts to re-think methods to monitor gestational
      drug exposures. In addition, the problem's persistence despite initial publicity
      suggests that diligent surveillance may require continued follow-up of identified
      safety issues. Periodic reassessments of selected preventable problems might
      strengthen efforts to minimize product risks.

PMID- 12512241
TI  - Adverse events in users of sertraline: results from an observational study in
      psychiatric practice in The Netherlands.
AB  - PURPOSE: To evaluate the safety profile of sertraline versus other Selective
      Serotonin Reuptake Inhibitors (SSRIs) directly following the introduction of
      sertraline to the Dutch market. METHODS: In a prospective follow-up study, 109
      psychiatrists included patients with a new episode of treatment with sertraline
      and an equal number of patients starting treatment with other SSRIs. All Adverse
      Events (AEs) during follow-up were recorded by the psychiatrists for the duration
      of SSRI treatment until discontinuation or until at least 12 months. RESULTS: A
      total of 1251 patients were included in the study of which 659 used sertraline
      and 592 used other SSRIs (paroxetine, fluoxetine or fluvoxamine). The most
      frequently reported events in sertraline users and users of other SSRIs were
      nausea (160 (24.3%) sertraline patients versus 160 (27.0%) patients using other
      SSRIs), headache (127 (19.3%) sertraline patients versus 101 (17.1%) patients
      using other SSRIs), diarrhoea (94 (14.0%) sertraline patients versus 40 patients
      using other SSRIs (6.8%, p < 0.05)), sweating (88 (13.4%) sertraline patients
      versus 69 (11.7%) patients using other SSRIs) and dizziness (75 (11.4%)
      sertraline patients versus 70 (11.8%) patients using other SSRIs). A total of 121
      patients reported 134 different unlabelled AEs of which 10 were reported by more
      than 1% of the population. CONCLUSIONS: In this study we found that almost three
      out of four patients reported an adverse event. When comparing with other SSRIs
      and the literature, we found a similar distribution of the most frequently
      reported adverse events in patients using sertraline. However, in this
      observational study we found over 100 different unlabelled adverse events.

PMID- 12512242
TI  - Misclassification of current benzodiazepine exposure by use of a single baseline
      measurement and its effects upon studies of injuries.
AB  - PURPOSE: Measurement of drug exposure is a major methodologic challenge for
      pharmacoepidemiologic studies of acute effects of medications taken
      intermittently. If the effect is plausible only during periods of active drug
      use, daily (or even more frequent) exposure measurement is optimal.
      Benzodiazepines, episodically used hypnotics and anxiolytics, impair psychomotor
      function and some epidemiologic studies have reported users have increased risk
      of unintentional injuries. However, several prospective cohort studies of this
      question defined benzodiazepine exposure status from a single baseline
      measurement, and these have not consistently reported increased risk. We used
      data from an historical cohort study to demonstrate the extent of
      misclassification potentially induced by this practice. METHODS: The cohort
      consisted of 2510 Tennessee nursing home residents 65 years of age or older
      identified in a prior study of antidepressants and falls. Both baseline users
      (any in 7 days preceding start of follow-up) and current use (use on a given day
      of follow-up) of benzodiazepines were determined from facility medication
      administration records, which record information on drugs given to the resident
      each day. Falls were ascertained from nursing home incident reports and medical
      records. The effect of benzodiazepine exposure for each ascertainment method was
      estimated from incidence rate ratios adjusted for multiple fall risk factors by
      Poisson regression. RESULTS: The 666 baseline benzodiazepine users had current
      use on 44.6% (95% CI, 40.2-49.2%) of follow-up person-days; baseline non-users
      had current use for 3.7% of days (2.8-4.7%). Misclassification increased with
      length of follow-up and with quintile of fall risk. The adjusted fall incidence
      rate ratios for the baseline user and current use definitions were 1.02 (95% CI,
      0.95-1.10) and 1.44 (1.33-1.56), respectively. CONCLUSION: These findings
      strongly suggest that to avoid potentially serious misclassification, studies of
      the acute effects of benzodiazepines and other drugs taken intermittently need to
      track exposure on a day-by-day basis.

PMID- 12512243
TI  - Patterns and perceptions of complementary and alternative medicine (CAM) among
      leukaemia patients visiting haematology clinic of a north Indian tertiary care
      hospital.
AB  - PURPOSE: The use of complementary and alternative medicine (CAM) in cancer
      treatments is widespread with substantial number of patients deserting
      conventional cancer therapies in favour of unproven methods. The present study
      aimed at discovering the prevalence of use of CAM cancer therapies in leukaemia
      patients visiting haematology clinic of a north Indian tertiary care hospital.
      METHODS: 533 consecutive leukaemia patients were interviewed. Information was
      gathered about patients' demographics, types of CAM taken, sequence of seeking
      CAM and conventional medicine, sources of recommendation, reasons of opting for
      CAM, and areas of satisfaction and dissatisfaction associated with the use of
      CAM. Patients were also asked if they had informed their doctor about CAM use.
      RESULTS: Prevalence of CAM use in leukaemia patients was found to be 56.6%.
      Ayurveda was the most commonly used CAM (33%). Most of the patients sought
      conventional medicine first, followed by CAM therapies. Fifty-two percent of the
      patients opted for CAM hoping for a miracle cure and 51% were dissatisfied with
      these therapies. Family members and neighbours constituted major source of
      recommendation of CAM therapy. Only 3.8% of the patients had informed their
      doctors about CAM use. CONCLUSION: A sizeable percentage of patients receiving
      conventional treatment for leukaemia also use CAM therapies. Clinicians should
      not underestimate the value of hopeful attitude in their management of leukaemia
      patients and ought to be conversant with popular forms of CAM cancer therapies.

PMID- 12512244
TI  - A survey of physician efficacy requirements to plan clinical trials.
AB  - PURPOSE: Eliciting physician efficacy requirements for utilizing medical
      treatments can be a useful means of helping plan a clinical trial. Efficacy
      requirements were studied for female stress urinary incontinence, where an
      experimental treatment (collagen injection) was compared to the standard therapy
      (surgery). METHODS: A self-administered questionnaire was sent to 223 North
      American urologists, gynecologists, and urogynecologists. An interviewer also
      administered a similar questionnaire to 20 other clinician-specialists. RESULTS:
      The response rate for the self-administered questionnaire was 48.4% (108/223).
      All 20 clinician-specialists who were approached for an interview consented. On
      average, respondents to the self-administered questionnaire indicated they would
      consider using collagen as the first line treatment if the absolute reduction in
      efficacy of collagen versus surgery was no larger than 23%. The corresponding
      result for the interview-questionnaire was 22%. Efficacy was measured as patient
      satisfaction with treatment. In the opinion of the physicians, surgery would
      remain the standard therapy if the reduction was greater than 34% (self
      administered questionnaire), or 37% (interviewer-administered questionnaire).
      CONCLUSIONS: The elicitation of physician efficacy requirements provides an idea
      of the treatment effect that would be needed for a clinical trial to have an
      impact on medical practice. These requirements can be used to calculate a
      relevant sample size.

PMID- 12512245
TI  - Frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and
      aspirin in US women.
AB  - PURPOSE: To determine the frequency of use of the three main classes of over-the
      counter analgesics: acetaminophen, non-steroidal anti-inflammatory drugs, and
      aspirin in two large US female cohorts. METHODS: We conducted a cross-sectional
      study of the frequency of analgesic use and the characteristics of users in
      female participants in the Nurses Health Study I (n = 86,985) and the Nurses
      Health Study II (n = 93,002) who were between the ages of 33 and 77 years.
      Information on frequency of current analgesic use was assessed by mailed
      questionnaire. RESULTS: All three classes of analgesics were used frequently. For
      example, acetaminophen was used > or = 1 day/week by more than 20% of women.
      NSAIDs were used > or = 1 day/week by 42% of women aged 51 years or younger, and
      aspirin was used > or = 6 days/week by 25% women over age 51 years. The frequency
      of use of the individual analgesics varied by age (p < 0.001). In addition, women
      in the highest category of use of any of the analgesics tended to have a higher
      body mass index, were more likely to have hypertension and diabetes, and were
      more likely to be current smokers. CONCLUSIONS: Analgesic use is very common
      among US women. Physicians should be cognizant of the frequency of use of the
      various over-the-counter analgesics in their female patient population.

PMID- 12512246
TI  - An approximate Bayesian risk-analysis for the gastro-intestinal safety of
      ibuprofen.
AB  - PURPOSE: Although several studies on ibuprofen and its gastro-intestinal (GI)
      risk have been reported, the dose-response relationship was not clear due to the
      lack of information regarding high-dose exposure. Analysis using Bayesian methods
      is appropriate whenever data are sparse, although such methods are not easily
      implemented. METHODS: A retrospective cohort study to assess this dose-response
      relationship was carried out using a record linkage database. A Bayesian risk
      analysis was conducted using the Bayesian bootstrap approximation. Risks of GI
      events at different dose levels were compared using the posterior distributions
      and the number of events predicted to occur in the future was estimated. Risk
      factors such as age, gender and co-morbidity were adjusted for in the analysis.
      This approximation was compared with the full Bayesian approach using the usual
      but more computer-intensive tool of Markov Chain Monte Carlo simulation. RESULTS:
      There were 1, 5 and 10 complicated GI events during exposure to high, medium and
      low dose ibuprofen with 0.2, 1.8 and 7.0 thousand person-years (PY) exposure,
      respectively. After adjusting for other risk factors the relative risks of high
      versus low and medium versus low doses were 6.3 (95% CI = 0.21, 24.17) and 2.5
      (95% CI = 0.71, 5.85), respectively. Using the approximate Bayesian method
      prediction of the number of events in a population of females aged 50-59 with no
      previous medical problems with 1000 PY drug exposure showed that the estimated
      probability of having more than five events was 0.048 for the medium-dose group
      and 0.14 for the high-dose group. CONCLUSIONS: High dose ibuprofen appears to
      have a considerably greater risk of having a larger number of adverse GI events
      than a medium dose. The approximate Bayesian bootstrap method was demonstrated to
      be a robust and easily implemented alternative to the full Bayesian approach to
      risk analysis whenever data are sparse.

PMID- 12512247
TI  - Characteristics of diarrhoea in 10,008 users of lansoprazole in daily practice:
      which co-factors contribute?
AB  - PURPOSE: Diarrhoea is one of the most frequently reported adverse events during
      proton pump inhibitor use in any setting. Because of the limited available
      information, this study was set up with the aim of assessing the incidence and
      characteristics of diarrhoea and to investigate possible associated co-factors in
      proton pump inhibitor users in daily practice. METHODS: Data were used from a
      prospective, observational study in which 10,008 lansprazole users were followed
      over time (1994-1998). The study was designed according to the SAMM guidelines. A
      nested case-control design was used to compare proton pump inhibitor users
      reporting diarrhoea with those reporting no diarrhoea. RESULTS: The frequency of
      diarrhoea was 3.7% and the incidence density 10.7 per 1000 patients months of
      proton pump inhibitor use. The diarrhoea was most commonly loose and occurred on
      average 4.4 times per day. The analysis of co-factors revealed that patients with
      concomitant use of oral antibiotics and patients reporting neurological and/or
      dermatological adverse events, were at risk of developing diarrhoea during proton
      pomp inhibitor use. CONCLUSIONS: In conclusion, diarrhoea was as frequently
      reported in our study as in clinical trials and observational data of
      lansoprazole users. We found the concomitant use of oral antibiotics and the
      reporting of certain other adverse events to be associated with the reporting of
      diarrhoea during lansoprazole use. Although a relationship with the proton pump
      inhibitor intake seemed very plausible, we recommend that use of concomitant
      medicines as a cause of diarrhoea must be taken into consideration in
      lansoprazole users.

PMID- 12512248
TI  - Use of ICD-9 coding as a proxy for stage of disease in lung cancer.
AB  - OBJECTIVE: To determine the validity of using ICD-9-CM codes indicating
      metastases as a proxy to classify lung cancer patients by stage of disease.
      RESEARCH DESIGN: This retrospective database analysis used diagnosis codes to
      classify subjects to either localized or advanced-stage disease and then compared
      this classification to the tumor registry staging, which was considered as the
      'gold standard.' SUBJECTS AND MEASURES: Study subjects included all lung cancer
      patients treated at our academic institution during 1996-1997, who were also
      members of a large insurance company. Data were derived from inpatient cancer
      related claims linked with our institution's tumor registry data. Advanced-stage
      disease (stages II to IV) was defined by claims indicating lymph node involvement
      or metastases (ICD-9 codes 196-199.1). The tumor registry stagings of the disease
      for these patients were clustered into two groupings, stages 0-I (localized) and
      stages II-IV (advanced). RESULTS: Tumor registry entries were identified for
      66/77 (85.7%) patients. A total of 19 out of 22 local disease patients
      (sensitivity of 86.4%) and 30 out of 44 advanced disease patients (sensitivity of
      68.2%) were classified correctly by ICD-9 code. A total of 19 out of 33 patients
      with local disease codes (PPV of 57.6%) and 30 out of 33 patients with advanced
      disease codes (PPV = 90.9%) were properly identified. CONCLUSIONS: For a
      population of lung cancer patients in an academic institution who were under a
      private insurance plan, the ICD-9 coding was associated with a sensitivity and
      positive predictive values that were consistent with previously reported
      estimates using Medicare-SEER data. The use of such data to classify patients to
      disease stages should be executed with caution as under-reporting might exist.
      Continued attention to discharge abstracting will be needed to improve the
      validity of this technique.

PMID- 12512249
TI  - Budesonide-treated asthmatic adolescents attain target height: a population-based
      follow-up study from Sweden.
AB  - PURPOSE: To examine final height in relation to target height in asthmatic
      patients with and without glucocorticoid treatment while growing up compared with
      healthy individuals. METHODS: In 1990 and 1993, questionnaires were distributed
      to all individuals born in 1974 and 1977 in the counties of Jamtland and
      Gastrikland in Sweden. All individuals reporting use of anti-asthmatic drugs or
      symptoms indicating possible obstructive airway disease, and a sample of healthy
      volunteers were invited to a clinical examination. RESULTS: Overall, 356
      asthmatic patients and 384 healthy individuals were identified. In 1998-1999, all
      subjects were invited to a follow-up study and final height was analysed in
      relation to target height in 152 asthmatic patients and 131 healthy individuals.
      It was found that both men and women achieved a higher mean final height than the
      calculated mean target height. There were no significant differences between
      controls and asthma patients treated either with or without glucocorticoids. Most
      of the patients treated with glucocorticoids started their therapy during
      adolescence and 92% had used inhaled budesonide. There was no trend towards a
      decrease in final height in relation to target height when inhaled budesonide
      treatment was initiated prior to adolescence or with lifelong cumulative dose of
      inhaled budesonide. CONCLUSIONS: Asthmatic adolescents treated with inhaled
      budesonide achieve normal final height in relation to their target height.

PMID- 12512251
TI  - Pharmacoepidemiology and drug safety.

PMID- 12512250
TI  - New approaches to analysing prescription data and to transfer
      pharmacoepidemiological and evidence-based reports to prescribers.

PMID- 12512252
TI  - Investigations on rhizoplane Actinobacteria communities of papyrus (Cyperus
      papyrus) from an Egyptian wetland.
AB  - Wetlands have important global ecological functions, which include carbon storage
      and water interception. Wetland contributes to the maintenance of regional and
      global biodiversity. Though many important wetland ecological functions are based
      on microbial metabolism, we have scanty knowledge on microbial diversity in
      wetlands. Plant rhizoplane habitats are considered to harbor highly diverse
      bacterial communities. Most of the floating mats on river Nile are dominated by
      papyrus (Cyperus papyrus). Papyrus root samples were collected from a floating
      mat at the "Gold Island" inside the Nile River at Cairo, Egypt in February 1996
      and May 1997 in order to investigate the rhizoplane actinobacteria communities.
      The root-tip regions were cut off, repeatedly washed, macerated and plated. Using
      the plate-count technique with three actinobacteria media, an average of 2.1 x
      10(4) CFUg-1 root actinobacteria were obtained. All actinobacteria colonies were
      isolated, purified and investigated by classical and molecular methods. In the
      papyrus rhizoplane Streptomyces anulatus, Micromonospora sp., Rhodococcus luteus,
      Verrucosispora gifhornensis and Aureobacterium liquefaciens dominated, moreover
      Actinoplanes utahensis, and Str. diastaticus were also present. The physiological
      traits of the members of dominant groups revealed that these bacteria might be
      active in the rhizoplane and can be present there is their vegetative forms.

PMID- 12512253
TI  - Serotypes, virulence factors, antibiotic sensitivity, beta-lactamase activity and
      plasmid analysis of Salmonella from children with diarrhea in Tripoli (Libya).
AB  - A total of 21 Salmonella strains isolated in Libya (16 from children with
      diarrhea and 5 from healthy controls) were serotyped and studied for their cell
      invasive ability, production of cytotoxin, antibiotic susceptibility, beta
      lactamase activity and plasmid profiles. Eight different serotypes of Salmonella
      were identified: 6 S. saintpaul, 4 S. wien (1 from control), 2 S. newport, 2 S.
      muenchen (1 from control), 2 S. typhimurium (1 from control), 2 S. hadar (1 from
      control), 2 S. reading (1 from control), 1 S. kottbus. Twenty (95%) were positive
      in the invasiveness assay using HeLa cells, and all (100%) were negative for
      cytotoxin production in HT29 cells. More than 40% were resistant to ampicillin,
      cefalexin, cefamandole, cefoperazone, chloramphenicol, gentamicin, mezlocillin
      and trimethoprimsulphamethoxazole and 100% were susceptible to the new
      quinolones. Most (67%) of the strains harbored plasmids and 43% produced beta
      lactamase. A strong association was observed between the presence of more than
      one plasmid, beta-lactamase activity, and multiple-resistance to antimicrobial
      agents and serotypes S. saintpaul and S. wien. Curing experiments with acridine
      orange showed that 2 plasmids (33 and 1.4 megadaltons) might be responsible for
      the resistance to chloramphenicol and gentamicin. The present study demonstrated
      that multiple-resistant salmonellae are widespread in Libya and the resistance is
      mainly plasmid mediated.

PMID- 12512254
TI  - Bioconversion of poultry wastes. I--Factors influencing the assay and
      productivity of crude uricase by three uricolytic filamentous fungi.
AB  - The optimum temperature for biomass yield and uricase production by uricolytic
      fungi, Aspergillus terreus, A. flavus and Trichoderma sp. was at 30 degrees C.
      The time required for maximum production of uricase and biomass yield was 4 days
      for two Aspergillus species and 6 days for Trichoderma sp. The optimum pH was at
      6.4 for A. terreus and pH 6.6 for A. flavus and Trichoderma sp. The maximum
      fungal biomass yield was achieved in medium supplemented with 4% poultry waste.
      The best carbon sources for the production of uricase and mycelia yield were
      glycerol, sucrose and maltose by A. terreus, A. flavus and Trichoderma sp.,
      respectively. Uric acid was found to be the best nitrogen source for production
      and activity of uricase by the three tested fungi. The addition of some vitamins
      to the culture media increased the maximum biomass yield of all the isolates,
      although no significantly increased uricase production was found.

PMID- 12512255
TI  - Specific recognition of the replication origins of the kinetoplast DNA.

PMID- 12512256
TI  - Isolation and characterization of two types of actinophages infecting
      Streptomyces scabies MR13.
AB  - Two types of actinophages, phi S and phi L, were isolated from soil samples by
      using Streptomyces scabies MR13, a potato scab pathogen, as an indicator strain.
      The phages were partially characterized according to their physicochemical
      properties, plaques and particles morphology and their host-range. The host-range
      of these phages was narrow for phi S and wide for phi L. The adsorption rate
      constants of the phi S and phi L were 3.44 x 10(-9) and 3.18 x 10(-9) ml/min, and
      their burst sizes were 1.61 and 3.75 virions, respectively. One-step growth
      indicated that phi S and phi L have a latent period of 30 min followed by a rise
      period of 30 min. The temperate character of these phages was tested in other
      isolates of Streptomyces. Four of the phages (phi SS3, phi SS12, phi SS13 and phi
      SS17) were identified as temperate phages, since they were able to lysogenize
      SS3, SS12, SS13 and SS17. phi SS3, phi SS12 and phi SS13 were homoimmune, and
      they were heteroimmune with respect to phi SS17. The restriction barriers of
      lysogenic isolates (SS12, SS13 and SS17) interfered with the blockage of plaques
      formation by phages (phi SS12, phi SS13 or phi SS17) propagated on them, about
      75% of lysogenic isolates had restriction systems. The exposure of the lysogenic
      isolates (SS12, SS13 and SS17) to UV-irradiation prevented the possible
      restriction barriers of these isolates, and these barriers could be overcome.

PMID- 12512257
TI  - From yeast genetics to biotechnology.
AB  - Roots of classical yeast genetics go back to the early work of Lindegreen in the
      1930s, who studied thallism, sporulation and inheritance of wine yeast strains
      belonging to S. cerevisiae. Consequent mutation and hybridization of
      heterothallic S. cerevisae strains resulted in the discovery of life cycle and
      mating type system, as well as construction of the genetic map. Elaboration of
      induced mutation and controlled hybridization of yeast strains opened up new
      possibilities for the genetic analysis of technologically important properties
      and for the production of improved industrial strains, but a big drawback was the
      widely different genetic properties of laboratory and industrial yeast strains.
      Genetic analysis and mapping of industrial strains were generally hindered
      because of homothallism, poor sporulation and/or low spore viability of brewing
      and wine yeast strains [1, 2]. In spite of this, there are a few examples of the
      application of sexual hybridization in the study of genetic control of important
      technological properties, e.g. sugar utilization, flocculation and flavor
      production in brewing yeast strains [3] or in the improvement of ethanol
      producing S. cerevisiae strains [4]. Rare mating and application of karyogamy
      deficient (kar-) mutants also proved useful in strain improvement [5]. Importance
      of yeasts in biotechnology is enormous. This includes food and beverage
      fermentation processes where a wide range of yeast species are playing role, but
      S. cerevisiae is undoubtedly the most important species among them. New
      biotechnology is aiming to improve these technologies, but besides this, a
      completely new area of yeast utilization has been emerged, especially in the
      pharmaceutical and medical areas. Without decreasing the importance of S.
      cerevisiae, numerous other yeast species, e.g. Kluyveromyces lactis, Hansenula
      polymorpha, Pichia pastoris, Schizosaccharomyces pombe and Yarrowia lipolytica
      have gained increasing potentialities in the modern fermentation biotechnology
      [6]. Developments in yeast genetics, biochemistry, physiology and process
      engineering provided bases of rapid development in modern biotechnology, but
      elaboration of the recombinant DNA technique is far the most important milestone
      in this field. Other molecular genetic techniques, as molecular genotyping of
      yeast strains proved also very beneficial in yeast fermentation technologies,
      because dynamics of both the natural and inoculated yeast biota could be followed
      by these versatile DNA-based techniques.

PMID- 12512258
TI  - Engineering of polyketide synthases: how close are we to the reality?

PMID- 12512259
TI  - To the hundredth anniversary of the death of Moriz Kaposi (1837-1902).

PMID- 12512260
TI  - Anatomy and physiology of the upper airway.
AB  - Normal respiration involves a highly detailed neurophysiologic process that
      results in the exchange of inspired and expired air through various anatomic
      structures. An understanding of these structures is important to the clinician
      involved in maintaining or reestablishing the normal airway. The following
      anatomic discussion focuses on the features crucial for the establishment and
      maintenance of a tracheal airway.

PMID- 12512261
TI  - Pediatric upper airway and congenital anomalies.
AB  - Understanding the differences between the infant upper airway and the adult upper
      airway is important in properly managing the infant and pediatric airway. Proper
      history and physical examination and selection of the appropriate endotracheal
      tubes, LMAs, and laryngoscopes are key to managing the normal infant and
      pediatric airway. The difficult infant and pediatric airway requires planning,
      preparation, and teamwork. The LMA, the light wand, and fiberoptic bronchoscope
      are important tools for managing the difficult pediatric airway. Congenital
      syndromes associated with difficult airways pose a unique set of challenges.
      Postoperative problems include postextubation croup and obstructive sleep apnea.
      Extubating the infant or child with a difficult airway should be orchestrated as
      carefully as intubating the infant or child with a difficult airway.

PMID- 12512262
TI  - Upper airway diseases and airway management: a synopsis.
AB  - This article summarizes some of the more important upper airway conditions likely
      to affect airway management. A number of upper airway conditions may present
      difficult challenges to the anesthesiologist. For instance, infected airway
      structures may lead to partial airway obstruction, stridor, or even complete
      airway obstruction. Partial airway obstruction may be mild, as in snoring or
      nasal congestion, or may be more severe, perhaps requiring the use of airway
      adjuncts, such as a nasopharyngeal airway. Complete airway obstruction is usually
      managed by prompt intubation, but surgical airways are sometimes needed as a last
      resort.

PMID- 12512263
TI  - Obstructive sleep apnea in the adult obese patient: implications for airway
      management.
AB  - Adult obese patients with suspected or sleep test confirmed OSA present a
      formidable challenge throughout the perioperative period. Life-threatening
      problems can arise with respect to tracheal intubation, tracheal extubation, and
      providing satisfactory postoperative analgesia. Tracheal intubation and
      extubation decisions in obese patients with either a presumptive and/or sleep
      study diagnosis of OSA must be made within the context that there may be excess
      pharyngeal tissue that cannot be visualized by routine examination, and the
      literature indicates an increased risk of intubation difficulty. Regional
      anesthesia for postoperative pain control is desirable (although such management
      is not necessary or possible for many of these patients). If opioids are used for
      the extubated postoperative patient, then one must keep in mind an increased risk
      of pharyngeal collapse and consider the need for continuous visual and electronic
      monitoring. The exact management of each sleep apnea patient with regard to
      intubation, extubation, and pain control requires judgment and is a function of
      many anesthesia, medical, and surgical considerations.

PMID- 12512264
TI  - Approaches to managing the upper airway.
AB  - Anesthesiologists traditionally approach airway management and maintenance of a
      patent airway through translaryngeal techniques. Most of the techniques and
      devices routinely used in clinical practice (orotracheal intubation, nasotracheal
      intubation, laryngeal mask airway, Combitube, fiberoptic intubation, and so
      forth) maintain airway patency by way of manipulation of components of the upper
      airway. Successful maintenance of a patient airway involves a detailed
      understanding of the interaction of each device or technique with the structures
      of the upper airway. The goals of this article are to review the skills
      commensurate with successful recognition of airway problems and management of the
      patient with a known or suspected difficult airway.

PMID- 12512265
TI  - Facemask, nasal, and oral airway devices.
AB  - Although this article merely glances the surface of some of the more fundamental
      aspects of managing the simple airway, one can see that an exhaustive discussion
      would require much more space than allotted herein. Although the author has
      attempted to reflect in a more clinically relevant tone in text, the best and
      most effective way to learn and remember such techniques is to perform them
      together with an experienced clinician. Attention to detail, subtleties, and
      nuances of the basic airway techniques, along with a willingness to refine this
      lost art of airway management, will re-solidify the foundation of excellent
      anesthesia and airway management.

PMID- 12512266
TI  - Using the laryngeal mask airway to manage the difficult airway.
AB  - Before 1990, the choice of an airway device essentially was limited to the
      facemask or the endotracheal tube. Since then, a number of novel supraglottic
      airway devices have been developed. The laryngeal mask airway (LMA) was
      introduced to the United States in 1991 after 3 years of use in the United
      Kingdom and other countries. Today the LMA has a clearly established role as an
      airway device in the elective setting when neither the procedure nor the patient
      require tracheal intubation. Perhaps more importantly, the LMA also has proved
      extremely useful in managing the difficult airway. This article reviews the use
      of the various LMA devices to manage the difficult upper airway.

PMID- 12512267
TI  - The ProSeal laryngeal mask airway.
AB  - The ProSeal LMA is a major advance over the Classic LMA because of the following
      reasons: it allows ventilation at much higher airway pressures; it protects the
      lungs from aspiration and the stomach from gastric insufflation; it facilitates
      passage of a gastric tube and monitoring devices into the esophagus; it can be
      inserted like the Classic or Intubating LMA; it has its own built-in bite block;
      malposition is detected more readily; and, through use of techniques such as gum
      elastic bougie-guided insertion, correct positioning is almost guaranteed. The
      ProSeal can be considered a replacement device for the Classic LMA, but the
      Flexible LMA is still preferable for most intraoral procedures, and the
      Intubating LMA is still preferable whenever intubation is required. Limitations
      are that it is slightly more difficult to insert and requires more careful
      thought to use optimally.

PMID- 12512268
TI  - The Esophageal-Tracheal Combitube.
AB  - The ETC is an easily inserted, double-lumen/double-balloon supraglottic airway
      device. The major indication of the ETC is as a back-up device for airway
      management. It is an excellent option for rescue ventilation in both in- and out
      of-the-hospital environments and in situations of difficult ventilation and
      intubation. It is useful especially in patients with massive airway bleeding or
      limited access to the airway and in patients in whom neck movement is
      contraindicated. Continued airway management with an ETC that has been placed is
      a reasonable option in many cases. Having thus secured the airway, it may not be
      necessary to abort the anesthetic or to continue with further airway management
      efforts. In order to avoid serious trauma to the esophagus or airway, redesigning
      the ETC using a softer material for the tube is advisable.

PMID- 12512269
TI  - Special devices and techniques.
AB  - Management of the difficult airway remains one of the most challenging tasks for
      anesthesia care providers. Most airway problems can be solved with relatively
      simple devices and techniques, but clinical judgment borne of experience is
      crucial to their application. As with any intubation technique, practice and
      routine use improve performance and may reduce the likelihood of complications.
      Each airway device has unique properties that may be advantageous in certain
      situations, yet limiting in others. Specific airway management techniques are
      greatly influenced by individual disease and anatomy, and successful management
      may require combinations of devices and techniques.

PMID- 12512270
TI  - Fiberoptic airway management.
AB  - Despite many recent innovations in equipment for difficult airway management, it
      remains the leading cause of the most devastating adverse outcomes in anesthesia.
      Fiberoptic airway management is among the most versatile of techniques for
      difficult airway management. It requires a greater degree of skill than most
      other techniques, however. Training, practice, and adherence to a few basic
      principles are required. It is most frequently used when difficult airway
      management is predicted but also may be appropriate when unforeseen difficulty
      arises. It cannot be too strongly emphasized, however, that this technique takes
      time and should be entertained only if the anesthesia care provider is able to
      maintain adequate oxygenation and ventilation until the airway is secured.

PMID- 12512271
TI  - Traumatic complications of intubation and other airway management procedures.
AB  - Complications arising from intubation and other airway management procedures can
      have significant morbidity and mortality risks. With the increasing
      interventional techniques employed by the anesthesiologist to acquire and
      maintain an airway, there is a potential for increasing airway injury. Awareness
      of the potential "difficult" airway and employing the appropriate techniques to
      maximize airway visualization can minimize the risk of these complications.

PMID- 12512272
TI  - [Specific features of monitoring the characteristics of digital X-ray diagnostic
      systems].
AB  - The paper analyzes the specific features of monitoring the basic characteristics
      of formation of images in the digital X-ray diagnostic systems and considers the
      potentialities of transfer from traditional expert assessments to more objective
      and precise experimentally calculated methods.

PMID- 12512273
TI  - [Optimization of dynamic fuzziness and enhancement of image quality of an URI/230
      Amethyst digital image intensifier].
AB  - In X-ray diagnostic units, digital image intensifiers with a SSD matrix have
      recently been used instead of vacuum vidicons. Along with the well-known
      advantage of SSD matrixes, they fail to reach the capacities of vidicons in
      transmitting movable images. The authors consider that the way out of this
      situation is to use recursive filters and arithmetic logic devices. The
      automatically used filters are particularly original.

PMID- 12512274
TI  - [Increasing the anode characteristics of sharp-focused Coolidge X-ray tubes by
      changing from a high to a low vacuum].
AB  - The anode characteristics of up-to-date sharp-focused Coolidge X-ray tubes are
      analyzed. The reason for differences in the real anode characteristics from
      theoretical ones has been found to be a higher tube gas pressure than that
      accepted. There is evidence that there are new third-class X-tubes--electronic
      tubes with compensation for negative volumetric charge of electrons with positive
      gas ions.

PMID- 12512275
TI  - [Green-sensitive X-ray systems and specific features of working with them].
AB  - Green-sensitive intensifying screens and the similar X-ray films permit a drastic
      reduction in a dosage load on a patient and an increase in the sharpness of an
      image. Therefore there is a quest for introducing the above systems in Russian
      practice. The paper presents the relative characteristics of the systems
      ([symbol: see text]3) developed in the country and recommendations on their
      practical use: to increase anode voltage and to decrease exposure.

PMID- 12512276
TI  - [Quality control of X-ray screen-film sets in light of introduction of an
      international system of standards].
AB  - The up-to-date international standard ISO 9236-1 for control of X-ray screen-film
      sets is somewhat different from the Russian GOST 27048-86. The author's
      experimental findings have shown that the sensitivity of the sets, measured by
      the Russian procedure, is about 60 times higher than the international one and
      the mean gradient is 10-15% greater. It is best to apply the international
      standard to ensure the unity of measurements.

PMID- 12512277
TI  - [Layout for the control of the radiation and electrical characteristics of UKREKH
      X-ray apparatus].
AB  - The paper presents data on an [symbol: see text]KPEX X-ray apparatus and its
      diagram, outlines the operation of the device.

PMID- 12512278
TI  - [The ID-03 X-ray dosimeter for monitoring the radiation parameters of X-ray
      equipment in roentgenography].
AB  - The paper presents an [symbol: see text]-03 X-ray dosimeter designed by the
      Research Institute of Introscopy, Spektr Moscow Research-and-Production
      Association, for monitoring the radiation parameters of X-ray plants at
      roentgenography. A Si(Li)-based semiconductor detector with the p-i-n structure
      is used as a detector of X-ray radiation. The technical data of the dosimeter are
      given.

PMID- 12512279
TI  - [A portable miniature IMD-01 X-ray dosimeter for monitoring the dose power in
      radiodiagnosis].
AB  - The paper presents a portable miniature [symbol: see text]-01 X-ray dosimeter
      designed by the Research Institute of Introscopy, Spektr Moscow Research-and
      Production Association, for monitoring the power of a dose during X-ray
      diagnosis. The device ensures the monitoring of the power of a dose at the input
      of X-ray detectors of diagnostic apparatuses and, with the use of special
      methods, makes it possible to control the state of the protection devices of X
      ray diagnostic apparatuses. An ionization chamber is used as a detector of X-ray
      radiation. The technical data of the dosimeter are given.

PMID- 12512280
TI  - [Approximate methods for calculation of the likelihood of radiation
      complications. The generalized PKLQ method (GPKLQM)].
AB  - Search for rational schedules of radiation therapy for malignant tumors is a
      topical problem of modern radiology. It cannot be solved without prognostic
      estimates of radiation affecting tumor and normal organs and tissues. The aim of
      the study was to develop mathematical models to be used for approximate
      evaluation of radiation affecting a tumor focus and normal organs and tissues.
      This paper provides a theoretical rationale for the generalized PKLQ (GPKLQ)
      method for a random count of tumor tissue radio-resistant cells, which is based
      on the view of the effective count of radio-sensitive cells (the effective volume
      of a damage focus).

PMID- 12512281
TI  - [Russian X-ray diagnostic equipment at the exhibition "Public Health-2001"].
AB  - The basic characteristics of Russian equipment displayed at the Exhibition Public
      Health-2001 are given. Emphasis is laid on X-ray and fluorographic equipment.

PMID- 12512282
TI  - [Development of equipment for bone densitometry].
AB  - The paper reviews the development of osteodensitometric equipment. The
      comparative characteristics of techniques for densitometry are presented. Their
      advantages and disadvantages are assessed.

PMID- 12512283
TI  - [Roentgenological materials on the Russian market].
AB  - The paper outlines the qualitative parameters of radiographic medical films and
      methods of their evaluation by Russian and foreign experts. A classification of
      their films is presented. The Russian methods and equipment for film examination
      do not satisfy the objective testing of up-to-date radiographic materials.

PMID- 12512284
TI  - [Russian technical mammography equipment].
AB  - The paper presents data suggesting that there is a rise in breast cancer
      mortality rates and those on the state of technical provision of therapeutical
      and-prophylactic institutions with mammographic equipment in Russia, which allows
      recognition of early forms of this disease. Data on a Mammo-MT apparatus
      manufactured by the closed joint-stock company Meditsinskiye Tekhnologii Ltd.
      (Medical Technologies Ltd.) are given.

PMID- 12512285
TI  - [The closed joint-stock company "Amiko" (X-ray equipment)].
AB  - The paper presents data on the closed joint-stock company AMIKO: basic lines of
      its activities, history, manufactured and designed products.

PMID- 12512286
TI  - Primary immunodeficiencies caused by defects of cytokines and cytokine receptors.

PMID- 12512287
TI  - Intracellular detection of T-cell cytokines. Differentiation of TH1 and TH2
      cells.

PMID- 12512288
TI  - Analysis of cytokine profiles in human skin.

PMID- 12512289
TI  - Intracytoplasmic detection of proinflammatory cytokines and chemokines in
      monocytes by flow cytometry.

PMID- 12512290
TI  - Flow-cytometric immune function methodology for human peripheral blood dendritic
      cells.

PMID- 12512291
TI  - Evaluation of the frequency of virus-specific CD8+ T cells by cytokine flow
      cytometry.

PMID- 12512292
TI  - Detection of common cytokine and colony stimulating factor gene polymorphisms.

PMID- 12512293
TI  - Apoptosis induction by TRAIL.

PMID- 12512294
TI  - Angiogenic cytokines. Quantitative and functional analysis.

PMID- 12512295
TI  - Experimental strategies for combined suicide and immune cancer gene therapy. An
      overview.

PMID- 12512296
TI  - Gene therapy with plasmids encoding cytokine- or cytokine receptor--IgG chimeric
      proteins.

PMID- 12512297
TI  - Interferon-beta gene therapy for the treatment of arthritis.

PMID- 12512298
TI  - Gene gun-based in vivo gene transfer. Application to DNA vaccination.

PMID- 12512299
TI  - Purification of the eucaryotic heat-shock proteins Hsp70 and gp96.

PMID- 12512300
TI  - Genetic engineering of a recombinant fusion protein possessing an antitumor
      antibody fragment and a TNF-alpha moiety.

PMID- 12512301
TI  - Genetic engineering of dendritic cells by adenovirus-mediated TNF-alpha gene
      transfer.

PMID- 12512302
TI  - Retroviral transfer of T-cell receptor genes into human peripheral blood
      lymphocytes.

PMID- 12512303
TI  - Gene transfer to articular chondrocytes with recombinant adenovirus.

PMID- 12512304
TI  - Gene therapy of X-linked severe combined immunodeficiency.

PMID- 12512305
TI  - Gene transfer for generation of tumor and leukemia vaccines.

PMID- 12512306
TI  - Cytokine gene delivery into the central nervous system using intrathecally
      injected nonreplicative viral vectors.

PMID- 12512307
TI  - In vitro regulation of colony stimulating factor-mediated hematopoiesis in
      healthy individuals and patients with different types of myeloproliferative
      disease.

PMID- 12512308
TI  - In vitro generation of dendritic cells from cord blood CD34+ hematopoietic
      progenitors cells.

PMID- 12512309
TI  - Generation of transgenic T cells from human CD34+ cord blood cells.

PMID- 12512310
TI  - Ex vivo expansion of umbilical cord blood cells on feeder layers.

PMID- 12512311
TI  - Ex vivo production of cord blood CD34+ derived myeloid precursors after serum
      free static culture.

PMID- 12512312
TI  - Ex vivo expansion of hematopoietic stem cells.

PMID- 12512313
TI  - Large-scale ex vivo expansion of human megakaryocytes for clinical use.

PMID- 12512314
TI  - Cytokine-mediated expansion of human NOD-SCID-repopulating cells.

PMID- 12512315
TI  - Differentiation of human antigen-presenting dendritic cells from CD34+
      hematopoietic stem cells in vitro.

PMID- 12512316
TI  - Dendritic cell development from mobilized peripheral blood CD34+ cells.

PMID- 12512317
TI  - In vitro maturation of dendritic cells from blood progenitors.

PMID- 12512318
TI  - Generation of human type 1- and type 2-polarized dendritic cells from peripheral
      blood.

PMID- 12512319
TI  - Preparation of human dendritic cells for tumor vaccination.

PMID- 12512320
TI  - Generation of leukemic dendritic cells from patients with acute myeloid leukemia.

PMID- 12512321
TI  - Introduction to confocal microscopy.

PMID- 12512322
TI  - Direct-view high-speed confocal scanner: the CSU-10.

PMID- 12512323
TI  - Introduction to multiphoton excitation imaging for the biological sciences.

PMID- 12512324
TI  - Confocal microscopy: important considerations for accurate imaging.

PMID- 12512325
TI  - Multicolor laser scanning confocal immunofluorescence microscopy: practical
      application and limitations.

PMID- 12512326
TI  - Practical aspects of objective lens selection for confocal and multiphoton
      digital imaging techniques.

PMID- 12512327
TI  - Resolution of subcellular detail in thick tissue sections: immunohistochemical
      preparation and fluorescence confocal microscopy.

PMID- 12512328
TI  - Confocal fluorescence microscopy for Tetrahymena thermophila.

PMID- 12512329
TI  - Confocal imaging of Drosophila embryos.

PMID- 12512330
TI  - Confocal fluorescence microscopy of the cytoskeleton of amphibian oocytes and
      embryos.

PMID- 12512331
TI  - Confocal fluorescence microscopy measurements of pH and calcium in living cells.

PMID- 12512332
TI  - Confocal and nonlinear optical imaging of potentiometric dyes.

PMID- 12512333
TI  - Measurement of intracellular Ca2+ concentration.

PMID- 12512334
TI  - Running and setting up a confocal microscope core facility.
AB  - Confocal shared resource facilities are not only useful, but the way to go! With
      the equipment and its maintenance costing more and more each year, and the
      technology growing and expanding all the time, it is difficult, if not
      impossible, for individual researchers to keep pace. However, core facilities can
      offer the latest equipment and services for the newest techniques only when they
      are maintained properly and supported by researchers. Policies for the
      encouragement of core facilities are important considerations in the budgets of
      university departments. Researchers should be offered incentives to use core
      facilities rather than purchase their own instruments, equipment which often is
      neglected within just a couple of years. Core facility managers are trained and
      skilled operators of these highly technical pieces of equipment and are prepared
      to keep your facilities in the best possible condition--for the best possible
      results.

PMID- 12512335
TI  - Mitochondrial DNA structure and function.

PMID- 12512336
TI  - Oxidative phosphorylation: structure, function, and intermediary metabolism.

PMID- 12512337
TI  - Import of mitochondrial proteins.

PMID- 12512338
TI  - Mitochondrial disorders of the nervous system: clinical, biochemical, and
      molecular genetic features.

PMID- 12512339
TI  - Friedreich's ataxia.

PMID- 12512340
TI  - Wilson disease.

PMID- 12512341
TI  - Hereditary spastic paraplegia.

PMID- 12512342
TI  - Cytochrome c oxidase deficiency.

PMID- 12512343
TI  - Toxin-induced mitochondrial dysfunction.

PMID- 12512344
TI  - Parkinson's disease.

PMID- 12512345
TI  - Huntington's disease: the mystery unfolds?

PMID- 12512346
TI  - Mitochondria in Alzheimer's disease.

PMID- 12512347
TI  - Contributions of mitochondrial alterations, resulting from bad genes and a
      hostile environment, to the pathogenesis of Alzheimer's disease.

PMID- 12512348
TI  - Mitochondria and amyotrophic lateral sclerosis.

PMID- 12512349
TI  - Models of mitochondrial disease.

PMID- 12512350
TI  - Defects of beta-oxidation including carnitine deficiency.

PMID- 12512351
TI  - The mitochondrial theory of aging: involvement of mitochondrial DNA damage and
      repair.

PMID- 12512352
TI  - PCR detection of microbial pathogens. Introduction.

PMID- 12512353
TI  - Specificity and performance of diagnostic PCR assays.

PMID- 12512354
TI  - Pre-PCR processing of samples.

PMID- 12512355
TI  - Critical aspects of standardization of PCR.

PMID- 12512356
TI  - PCR technology and applications to zoonotic food-borne bacterial pathogens.

PMID- 12512357
TI  - Detection, identification, and subtyping of Actinobacillus pleuropneumoniae.

PMID- 12512358
TI  - Identification and differentiation of Brucella abortus field and vaccine strains
      by BaSS-PCR.

PMID- 12512359
TI  - Isolation of Campylobacter and identification by PCR.

PMID- 12512360
TI  - Detection and differentiation of  Chlamydiae by nested PCR.

PMID- 12512361
TI  - Detection of toxigenic clostridia.

PMID- 12512362
TI  - PCR-based detection of Coxiella burnetii from clinical samples.

PMID- 12512363
TI  - Detection and subtyping of Shiga toxin-producing Escherichia coli (STEC).

PMID- 12512364
TI  - Detection of Listeria monocytogenes using a PCR/DNA probe assay.

PMID- 12512365
TI  - Detection of Leptospira interrogans.

PMID- 12512366
TI  - Detection of pathogenic mycobacteria of veterinary importance.

PMID- 12512367
TI  - Multiplex PCR of avian pathogenic mycoplasmas.

PMID- 12512368
TI  - Detection and differentiation of ruminant mycoplasmas.

PMID- 12512369
TI  - Detection of Mycoplasma hyponeumoniae from clinical samples and air.

PMID- 12512370
TI  - PCR-detection of Hemophilus paragallinarum, Hemophilus somnus, Mannheimia
      (Pasteurella) hemolytica, Mannheimia spp., Pasteurella trehalosi, and Pasteurella
      multocida.

PMID- 12512371
TI  - Detection of Salmonella spp.

PMID- 12512372
TI  - Detection of Toxoplasma gondii.

PMID- 12512373
TI  - PCR-derived methods for the identification of Trichinella parasites from animal
      and human samples.

PMID- 12512374
TI  - Detection of pathogenic Yersinia enterocolitica by a swab enrichment PCR
      procedure.

PMID- 12512375
TI  - Cutaneous lesions.
AB  - Although not a substitute for histologic examination, lumps, bumps, and lesions
      of the skin and subcutis readily lend themselves to cytologic examination via
      FNB, fine-needle nonaspiration biopsy, imprinting, or scraping of lesions. These
      techniques are used to obtain cells that can be examined by a clinical
      pathologist or cytologist to provide a diagnosis, decide a course of therapy, or
      offer a prognosis. Although histologic and cytologic examinations do not always
      agree, many times there is excellent correlation between the two disciplines.
      There are few patients with cutaneous lesions that would not benefit from
      cytologic examination of their lesion.

PMID- 12512376
TI  - Lymph node cytology.
AB  - Lymph node cytology is quick, easy, and rewarding. Cytologic samples of
      peripheral and/or internal lymph nodes may be collected by fine-needle aspiration
      biopsy (FNAB) or nonaspiration fine-needle biopsy techniques. In addition,
      imprints or scrapings may be made from lymph nodes that have been surgically
      removed or at necropsy. Lymph node cytology is an excellent way to evaluate a
      lymphadenopathy whether it is a single node enlarged, multiple nodes enlarged, or
      a generalized lymphadenopathy. If multiple lymph nodes are enlarged, more than
      one should be sampled. A lymph node away from the mouth or any site of
      inflammation should be aspirated as well as any lymph node close to a site of
      inflammation. Generally, if no lymph nodes are enlarged, lymph node cytology is
      not helpful.

PMID- 12512377
TI  - Bronchoalveolar lavage.
AB  - Bronchoalveolar lavage is a valuable diagnostic technique when appropriate
      patient selection is made, which includes diseases that involve the pulmonary
      parenchyma and patients that can safely undergo general anesthesia.
      Bronchoalveolar lavage cytology has the potential to provide a definitive
      diagnosis or additional diagnostic information with a less invasive procedure
      than lung aspiration or thoracotomy. Limitations of accuracy in cell counts and
      negative findings are considerations when interpreting bronchoalveolar lavage
      fluid results.

PMID- 12512378
TI  - Abdominal, thoracic, and pericardial effusions.
AB  - The laboratory evaluation of abdominal, thoracic, and pericardial effusions is a
      useful diagnostic tool for the assessment of disease states that result in fluid
      accumulation. Although the numeric values pertaining to cell count and protein
      content are important, the microscopic evaluation is a critical aspect of the
      diagnostic procedure; not only does it allow complete classification of the fluid
      but it allows identification of specific cell types or microorganisms that might
      be responsible for the fluid accumulation. These findings should always be
      interpreted in conjunction with the history, signalment, physical findings, and
      other diagnostic aids in making a definitive diagnosis.

PMID- 12512379
TI  - Renal cytology.
AB  - FNA of renal tissue is a rapid and noninvasive diagnostic tool that can be
      optimized by a thorough understanding of renal diseases, anatomy, and the
      ultrasonographic appearance of lesions likely to exfoliate for cytology.
      Signalment, history, and ancillary laboratory tests can narrow the list of
      differential diagnoses and help to determine whether cytologic evaluation will be
      sufficient or whether tissue architecture is needed for a definitive diagnosis.
      Renal cytology is particularly useful for the diagnosis of inflammation and
      neoplasia, including abscesses, FIP, mycotic infections, lymphoma, carcinoma, and
      metastatic neoplasia.

PMID- 12512380
TI  - Cytology of the spleen.
AB  - Fine-needle aspiration of the spleen is a useful method for evaluation of
      reactive, inflammatory, and neoplastic disorders, particularly those that involve
      the hematopoietic system. Interpretation of splenic aspirates is enhanced by
      concurrent evaluation of blood and other hemic tissues.

PMID- 12512381
TI  - Laboratory evaluation and interpretation of synovial fluid.
AB  - Canine and feline joint disease can be a primary disorder limited to joints or a
      manifestation of multisystemic disease. Collection and analysis of joint fluid
      provides valuable information for the diagnosis, prognosis, and treatment of
      diseases that affect the joint space. The cytologic recognition of the cellular
      components and infectious agents in synovial fluid categorizes the cell response
      and differentiates inflammatory and noninflammatory joint disorders. This
      information is supported by the cell counts, protein content, mucin clot test,
      bacterial culture, and serologic tests for infectious or immune-mediated disease.
      These results are integrated with the clinical history, physical examination,
      radiographic findings, and ancillary test results to arrive at a diagnosis and
      treatment plan.

PMID- 12512382
TI  - Epithelial growth factor receptor interacting agents.
AB  - The data reviewed here have further established the promise of anti-EGFR-targeted
      therapies. This statement is supported by the evidence of antitumor activity of
      the TK inhibitors ZD1839 and OSI-774 against several tumor types and by the
      ability of the monoclonal antibody IMC-C225 to reverse clinical chemotherapy
      resistance. These results are further supported by an emerging number of
      compounds, monoclonal antibodies, and TK inhibitors directed at the EGFR that are
      in clinical development (see Fig. 2, Table 1). Among the TK inhibitors, these
      compounds can be further categorized by their receptor specificity and
      reversibility of binding. In the case of anti-EGFR monoclonal antibodies,
      compounds in clinical development include chimeric, humanized, and bispecific
      antibodies. The fundamental observation is that these compounds have shown
      activity in several tumor types, including NSCL cancer, prostate carcinoma,
      colorectal carcinoma, ovarian carcinoma, renal cell carcinoma, and head and neck
      cancers. These findings observed with different agents and in different tumor
      types validate EGFR as a target for cancer therapy. The results of ongoing
      studies with these agents in diverse indications and tumor types may establish
      the role of these promising therapies to our current cancer treatments.

PMID- 12512383
TI  - Inhibitors of the ras oncogene as therapeutic targets.
AB  - Advances in our understanding of the molecular pathways and genetic mutations
      that control tumor cell proliferation and metastasis present an opportunity to
      develop novel, mechanism-based therapeutic strategies. Ras mutations are the most
      frequently activated oncogenes in human tumors, with over 30% expressing ras
      mutations. Molecular dissection of the signaling pathway and the mechanisms of
      ras anchorage, post-translational modification, and downstream effector signaling
      of ras now under intensive investigation will help us to design additional
      methods for ras-directed therapy in an effort to reach an optimal treatment for
      human tumors that will most likely comprise a combination of modalities targeted
      at the different underlying genetic defects. The successes and limitations of ras
      targeted therapies must be viewed in light of the increasing understanding of the
      complexity of the ras-signaling pathway. Only now are we beginning to discover
      the many functions of this integrated pathway, such as the differences between
      the actions of various ras isoforms that may affect our choice of therapeutic
      approach. Many of these Ras therapeutic targets have shown success in preclinical
      studies, and some have shown efficacy in clinical trials with minimal toxicities.
      Compounds that block ras-transforming activity without affecting normal ras
      function seem more attractive for the future development of ras-targeted therapy.
      FTIs may partially fulfill such requirements. Based on their specific, novel, and
      mechanism-based action; minimal toxicity; and encouraging responses in clinical
      trials, the development of Ras therapeutic targets as single agents or in
      combination with conventional chemotherapy and radiotherapy should be pursued.

PMID- 12512384
TI  - Targeting intracellular signal transduction. A new paradigm for a brave new world
      of molecularly targeted therapeutics.
AB  - Significant advances in the field of molecular biology over the past decade have
      led to a new era in cancer therapeutics, with an explosion of rationally designed
      therapeutic strategies directed against selective molecular targets. The complex
      array of aberrant signal transduction proteins involved in carcinogenesis has
      been the focus of target-based anticancer agents. Inhibitors of intracellular
      signal transduction represent a unique approach in that they inhibit critical
      downstream regulatory proteins, which are vital to the process of cellular
      communication. Although these agents are in early-phase evaluations, the
      preliminary data suggest that they are well tolerated and capable of target
      inhibition in surrogate and tumor tissue. Although the primary therapeutic
      benefit of these agents is expected to be decreased tumor growth, evidence
      suggests that objective tumor responses may also be achieved. There are many
      unresolved questions pertaining to the development of this class of compounds,
      including selection of optimal dose and schedule, determination of relevant
      endpoints, methods for target validation, and strategies for combination with
      cytotoxic agents. However, despite the numerous unresolved issues, the emergence
      of this class of compounds has resulted in an undeniable impact on the present
      and future of cancer therapeutics.

PMID- 12512385
TI  - Clinical development of mammalian target of rapamycin inhibitors.
AB  - Rapamycin and CCI-779 have significant in vitro and in vivo anti-proliferative
      activity against a broad range of human tumor cell lines, justifying the clinical
      evaluation of this class of agent in cancer patients. Preliminary results from
      phase I studies of CCI-779 suggest that the agent is well tolerated and has anti
      tumor activity. The challenge to investigators is to efficiently determine what
      role this class of agent will play in the treatment of cancer patients.

PMID- 12512386
TI  - Targeting the molecular pathophysiology of gastrointestinal stromal tumors with
      imatinib. Mechanisms, successes, and challenges to rational drug development.
AB  - The development of imatinib as molecularly targeted therapy for GIST represents
      an important case study of rational drug development. It is a paradigm of how the
      molecular understanding of a cancer has resulted in a new effective therapy that
      targets the critical pathway upon which the GIST cells were dependent: the
      uncontrollably active KIT signaling pathway. Unresectable or metastatic GISTs
      have traditionally exhibited a rapid and fatal clinical course, with no evidence
      of benefit from any standard cytotoxic chemotherapy. The identification of KIT
      activation as a critical factor in the pathogenesis of GIST led to the search for
      a new type of therapeutic compound to serve as a KIT inhibitor and to interfere
      with the constitutive phosphorylation of the KIT kinase in GIST cells.
      Clarification of the molecular genetic pathophysiology of GIST and the role of
      KIT activation in this disease, therefore, has not only enabled improved
      diagnosis and differentiation of GIST from other mesenchymal neoplasms but has
      also been key in identifying new targeted strategies for therapeutic
      intervention. The improved understanding of the molecular pathophysiology of
      GIST, a disease that was previously untreatable with any available systemic
      therapy, has led to the development of imatinib, a well-tolerated agent that can
      inhibit the dysregulated KIT signaling pathways in GIST. Imatinib represents the
      first (and currently the only) effective systemic therapy for patients with
      unresectable GIST. Imatinib therapy can induce objective responses and
      stabilization of disease and can provide clinical benefit in the majority of GIST
      patients treated with the drug. Other strategies are beginning to be explored,
      such as the use of imatinib earlier the in course of GIST (e.g., as adjuvant
      therapy after definitive surgical resection of early-stage disease). Integration
      of signal transduction inhibitors into the armamentarium of cancer therapeutics
      will undoubtedly continue based on this important paradigm of GIST.

PMID- 12512387
TI  - Angiogenesis as a target for cancer therapy.
AB  - Antiangiogenic drugs are unique for having highly specific targets while carrying
      the potential to be effective against a wide variety of tumors. Moreover, some of
      the major limitations of cytotoxic therapies likely will be avoided by this
      entirely new class of anticancer weapons. After the realization of the potential
      advantages of antiangiogenic therapy, the field of angiogenesis research is
      growing exponentially. Still, there is much to learn about the machinery that
      tumors use to recruit new blood vessels, and the results of the clinical trials
      will show the best way to apply that knowledge for cancer therapy.

PMID- 12512388
TI  - Inhibitors of the vascular endothelial growth factor receptor.
AB  - The inhibitors of VEGF-mediated signaling continue to wind their way through
      extensive preclinical and clinical development paths. Whereas the first phase III
      trial did not meet its endpoints, one hopes that the others will. As we learn
      more about the VEGF pathways in the laboratory and the clinic, we can interpret
      with greater certainty what role these drugs or their successors will have in the
      treatment of human cancers.

PMID- 12512389
TI  - Development of matrix metalloproteinase inhibitors in cancer therapy.
AB  - The matrix metalloproteinases represent an attractive target for cancer
      treatment, and a number of matrix metalloproteinase inhibitors are undergoing
      clinical trials. The results of these studies will establish whether any of these
      compounds are therapeutically useful. Independent of the conclusions from the
      first generation of studies, the field of matrix metalloproteinase inhibitors
      remains attractive for creative and innovative research. In the future, the
      development of novel, less toxic, and more effective matrix metalloproteinase
      inhibitors, and the combination of conventional agents with these novel
      anticancer agents will constitute the main focus of research efforts.

PMID- 12512390
TI  - Cyclin-dependent kinases as new targets for the prevention and treatment of
      cancer.
AB  - Based on the frequent aberration in cell cycle regulatory pathways in human
      cancer by cdk hyperactivation, novel ATP competitive cdk inhibitors are being
      developed. The first two tested in clinical trials, flavopiridol and UCN-01,
      showed promising results with evidence of antitumor activity and plasma
      concentrations sufficient to inhibit cdk-related functions. Best schedule to be
      administered, combination with standard chemotherapeutic agents, best tumor types
      to be targeted, and demonstration of cdk modulation from tumor samples from
      patients in these trials are important questions that need to be answered to
      advance these agents to the clinic.

PMID- 12512391
TI  - Regulators of apoptosis as anticancer targets.
AB  - For the majority of patients with advance malignancies, current therapies are
      noncurative. Developing therapeutic agents that enhance the apoptotic effects and
      hence antitumor potential of currently available chemotherapy agents represents a
      rationale investigative strategy. Several chemotherapeutic agents including
      antimicrotubule agents and all-trans-retinoic acid utilize these pathways to
      mediate tumor cell killing. With specific agents such as oblimersan sodium in
      randomized "pivotal" studies, and agents targeting the TRAIL receptor-family
      recently entering early clinical study, cautious optimism is warranted.

PMID- 12512392
TI  - Heat shock protein and proteasome targeting agents.
AB  - Proteasome inhibitors such as PS-341 are novel agents with great potential as
      anticancer drugs. In early clinical studies, PS-341 was tolerated well with
      promising evidence of antitumor activity in diseases such as multiple myeloma.
      Studies also are ongoing in solid tumors, as single agent therapy and in
      combination with standard agents such as carboplatin. Although more research is
      needed to clarify the precise spectrum of antitumor activity of proteasome
      inhibitors, this novel approach to targeting human malignancies is highly
      promising.

PMID- 12512393
TI  - Clinical trial designs for targeted agents.
AB  - With an increasing number of targeted agents available for testing, clinical
      trials must be rationally designed based on sound knowledge of the molecular
      mechanisms linking target and disease, fortified by strong preclinical data
      demonstrating how this relationship is modified by the targeted agent. Patients
      and resources are precious and should be expended judiciously on clinical trials
      that are well planned. Although traditional trial designs and endpoints may not
      be adequate for developing contemporary targeted drugs, transiting directly from
      phase I to phase III testing should be avoided except in distinct circumstances.
      Increased research efforts should be spent on the prospective evaluation and
      validation of novel biologic endpoints and innovative clinical designs, such that
      promising targeted agents can be effectively developed to benefit the care of
      cancer patients.

PMID- 12512394
TI  - Asperger syndrome.

PMID- 12512395
TI  - Asperger syndrome: diagnosis and external validity.
AB  - This article provides an overview of the history and clinical features of
      Asperger syndrome and considers guidelines for clinical assessment and treatment.
      A review of issues related to external validity is provided that points out the
      limitations of current research and lists several potentially beneficial areas of
      investigation into the nosologic status of the condition. It concludes with a
      discussion of the unequivocal need of individuals with severe social disabilities
      for comprehensive and adequate educational services and other treatments,
      regardless of the fact that the validity and usefulness of this specific
      diagnostic concept is far from resolved.

PMID- 12512396
TI  - Epidemiologic data on Asperger disorder.
AB  - In 1944, Asperger described a syndrome that was subsequently given his name,
      although there is evidence from earlier European literature that clinical
      descriptions matching this disorder were available in the 1920s. Asperger's work
      was largely ignored until the seminal article by Wing, however, which led to a
      resurgence of interest in this diagnostic concept. Asperger disorder (AD) was
      only introduced as a separate diagnostic category in the latest revisions of ICD
      10 and DSM-IV. Epidemiologic research on this disorder has only started in recent
      years and therefore data are still scarce on the prevalence of this syndrome.
      This article reviews available epidemiologic surveys that have shed light on the
      prevalence of AD.

PMID- 12512397
TI  - Strategies for pharmacologic treatment of high functioning autism and Asperger
      syndrome.
AB  - The treatment of complex, polymorphous disorders like HFA/AS always brings a
      particular challenge to pharmacotherapy. Additionally, the specific
      characteristics presented by HFA/AS introduce unique complications to patient
      care and place unusual demands on a clinician's skill and experience. To provide
      safe and effective treatment, the clinician must understand the core features of
      the disorder and the manifestations of the condition in his or her patient.
      Furthermore, a thorough understanding of the family, school, and community
      resources and limitations is necessary. Once an assessment has been made,
      focusing on target symptoms provides a crucial framework for care. Knowing
      manifestations of symptoms and characterizing their distribution and behavior in
      that patient is most important. For patients with HFA/AS it is particularly
      essential to coordinate behavioral and pharmacologic objectives. The target
      symptoms should be tracked carefully and placed into a priority system that is
      based on the risks and disability they create for the patient. The skill of
      pharmacotherapy also means setting out realistic expectations, keeping track of
      the larger systems of care at school and home, and collaboration with parents and
      care providers. There is an expanding range and pace of biologic and intervention
      research into HFA/AS. The genetic work has produced exciting leads that are
      likely to be helpful to future generations [82-84], but the task of clinicians is
      to tend to today's patients. As we discover more about the complex neural
      circuitry subserving repetitive behaviors, reward systems, and social cognition,
      there are good reasons to believe our treatments will become more sophisticated
      and specific. Psychopharmacology is also moving to design medications that target
      more specific populations of receptor and brain functions. This is likely to
      produce medicines that have fewer side effects, are more effective, and are more
      symptom-specific. Pharmacotherapy is not the ultimate treatment for HFA/AS but it
      has a definite place. Medication can be a critical element in a comprehensive
      treatment plan. There is a wider range of medications with more specific biologic
      effects than ever before. For patients with HFA/AS these newer agents are safer
      and less disruptive. When paired with clinicians who are becoming more skilled at
      recognizing and managing symptoms, patients have a greater opportunity to reach
      their potential and lead pleasurable lives.

PMID- 12512398
TI  - Outcome research in Asperger syndrome and autism.
AB  - This article presents findings from the outcome literature on autism, Asperger
      syndrome (AS), and related disorders. The discussion of outcome principally
      focuses on life adaptation, but also considers outcome in AS in relationship to
      other diagnostic groups and across time. The current research in this area is
      neither substantial nor systematic. Thus, in this examination of the literature,
      the goal is to highlight salient findings, but also to put forward questions that
      might direct meaningful research in this area for the future and to consider
      implications for treatment.

PMID- 12512399
TI  - Frameworks for behavioral interventions.
AB  - This article examines two frameworks for behavioral interventions, namely the
      developmental stages in friendship skills with remedial strategies for each
      stage, and modifications to Cognitive Behavior Therapy to accommodate the unusual
      profile of cognitive skills of people with Asperger disorder.

PMID- 12512400
TI  - Promoting social communication in high functioning individuals with autistic
      spectrum disorders.
AB  - This article reviews a range of social communication interventions that have been
      developed for students with autism at the preschool, school age, and adolescent
      level. Adult-mediated and peer-mediated methods that use highly structured, child
      centered, and hybrid methods are examined. Programs that provide information on
      generalization and maintenance are identified. A set of recommendations for
      programs that would seem to be most appropriate for students with Asperger
      syndrome is presented.

PMID- 12512401
TI  - Social skills interventions for the autism spectrum: essential ingredients and a
      model curriculum.
AB  - This article outlines the ingredients the authors feel are critical to making
      social skills interventions successful for children with autism spectrum
      disorders. The authors described basic principles for teaching social skills that
      capitalize on the strengths of such children, while specifically addressing their
      deficits. The authors applied these widely used principles to group social skills
      intervention. In particular, social skills groups for children with ASD need to
      break down complex social behaviors into concrete steps and rules that can be
      memorized and practiced in a variety of settings. Abstract concepts must be made
      concrete through a variety of visual, tangible, "hands-on" activities that make
      socialization fun. Visual structure and predictable routines are essential. Also
      critical to the success of social skills intervention are instruction and
      activities that provide necessary support for the language abilities of the
      participants. A variety of learning opportunities must be used to teach the goals
      and skills most relevant to children with ASD. These skills must be integrated as
      intervention progresses. Furthermore, interactions that require the children to
      focus on peers create a positive social group culture. Within this culture and
      environment, self-awareness and positive self-esteem can be fostered. A behavior
      plan that specifies individual goals for group members and a specific system for
      delivering rewards should be included. Other important ingredients include
      generalization, which is encouraged through community outings, skill practice in
      more naturalistic settings, and collaboration with parents and teachers to work
      on skills outside the group intervention. Weekly therapy does little to change
      basic deficits of ASD unless there is daily practice and reinforcement of the
      skills being learned in more natural situations. The authors hope that outlining
      these principles and specific techniques will encourage more clinicians to offer
      social skills groups and thus increase their availability around the nation and
      world. Continued research and treatment for social skills is necessary to provide
      much needed empiric evidence to determine effectiveness of such interventions.

PMID- 12512402
TI  - Behavioral forms of stress management for individuals with Asperger syndrome.
AB  - Although many children and youth with AS exhibit anxiety that may lead to
      challenging behaviors, stress and subsequent behaviors should be viewed as an
      integral part of the disorder [36]. As such, it is important to understand the
      cycle of behaviors to prevent seemingly minor events from escalating. Although
      understanding the cycle of tantrums, rage, and meltdowns is important, behavior
      changes will not occur unless the function of the behavior is understood and the
      student is provided instruction and support in using (1) strategies that increase
      social understanding and problem solving, (2) techniques that facilitate self
      understanding, and (3) methods of self-calming. Because little research exists on
      the cycle of behaviors exhibited by students with AS and interventions
      appropriate at each stage, a systematic program of research is required to
      identify which techniques are most appropriate for children and youth, the
      context in which they can be used, and methods to ensure that individuals with AS
      generalize these skills to home, school, and community.

PMID- 12512403
TI  - The challenge of adolescents and adults with Asperger syndrome.
AB  - Despite the rapid growth of interest in Asperger disorder in children, there
      continues to be a lack of awareness of the diagnosis and its implications for
      adolescents and adults. The reasons for this lack of awareness lie in the history
      of the disorder and in the historical development of mental health services.
      Because, as Santayana wrote, "Those who cannot remember the past are condemned to
      repeat it," this article reprises some of the history given elsewhere in this
      issue, but in a highly partial way, to bring out what the author believes to be
      the historically grounded prejudices that are the first challenge to anyone
      wanting to help adolescents and adults with Asperger syndrome.

PMID- 12512404
TI  - Viscosupplementation for the arthritic ankle.
AB  - HA is, in large part, responsible for the viscoelastic properties of synovial
      fluid that are critical to normal joint function. In OA, the concentration and
      molecular weight of HA are diminished. The intra-articular injection of exogenous
      HA preparations, termed viscosupplementation, has been shown to be safe and
      efficacious for use in the treatment of OA of the knee. There seem to be many
      mechanisms of action in addition to the transient restoration of joint fluid
      viscoelastic properties. These include anti-inflammatory, anabolic, analgesic,
      chondroprotective, and anticatabolic effects. Anecdotal use in OA of the ankle
      has been encouraging, but larger scale, controlled studies need to be performed.
      In addition, long-term investigations will better define the duration of
      effectiveness that viscosupplementation provides and whether it is a cost
      effective modality.

PMID- 12512405
TI  - Absorbable implants in fracture management.
AB  - The use of absorbable implants has been studied extensively in the clinic and the
      laboratory. The limitations of absorbable implants are now well-known and include
      a finite life span and strength profile, the possible development of an
      inflammatory response, and their limitation to use in fractures that do not
      require traditional compression techniques. Advantages of these implants include
      the lack of necessity for removal at a later date, which has cost savings
      potential, their ease of use, and their strength, which may be sufficient for
      healing in certain situations. The most likely scenarios for the use of these
      implants in fracture management of the foot and ankle include syndesmotic
      disruptions, dislocations about the midfoot, and fractures of the medial
      malleolus.

PMID- 12512406
TI  - Treatment of tendon disorders. Is there a role for corticosteroid injection?
AB  - Tendon injuries and other tendon disorders are a source of major concern in
      competitive and recreational athletes and in many working conditions requiring
      repetitive movements. The exact etiology, pathophysiology, and healing mechanisms
      of the various tendon complaints are, however, only partly known and even origin
      of pain in the chronic tendon disorders is unknown. Thus, the treatment
      strategies recommended for tendon complaints vary considerably and the given
      treatment is frequently based on empirical evidence only. Corticosteroid
      injections are one of the most commonly used treatments for chronic tendon
      disorders. Despite their popularity, the biologic basis of their effect and the
      systematic evidence for their benefits are largely lacking. In addition to
      suppressing inflammation, the effects of local corticosteroid injections could be
      mediated through their effect on the connective tissue and adhesions between the
      tendon and the surrounding peritendinous tissues by inhibiting the production of
      collagen, other extracellular matrix molecules, and granulation tissue in these
      sites. Also, if the pain in tendinopathy is a result of stimulation of
      nociceptors by chemicals released by the damaged, degenerated tendon,
      corticosteroids might mediate their effect thorough alterations in the release of
      these noxious chemicals, the behavior of these receptors, or both. Achilles
      tendinopathy, rotator-cuff tendinopathy, tennis elbow, and trigger finger are
      among the most frequent tendon problems. There is good evidence, however,
      strongly supporting the use of local corticosteroid injections in the trigger
      finger only. This can be to the result of either a true lack of the effect or
      just a lack of good trials in the other complaints. Intimidation with adverse
      effects of peritendinous corticosteroid injections is based on case reports only
      rather than convincing data from controlled clinical studies. In light of the
      animal studies, corticosteroid injection into tendon substance should be avoided,
      although the true incidence of side effects after local corticosteroid
      injection(s) for tendon disorders is unknown. Also, the relevance of the steroid
      used, the tissue affected, the extent of the tendon problem, the duration of the
      symptoms, the phase of healing at the time of injections, and the postinjection
      events remain undetermined. Although a complete tendon rupture with loading after
      steroid injection has been reported, no reliable proof exists of the deleterious
      effects of peritendinous injections; conclusions in literature are based mainly
      on uncontrolled case reports that fail under scientific scrutiny, whereas
      scientifically rigorous studies have not been performed. An acute tendon disorder
      often responds favorably to early intervention with conservative treatment
      modalities. Local corticosteroid injections gives good short-term results in
      prolonged or subacute cases that do not respond to the conventional conservative
      treatments. Although corticosteroid injections are one of the most commonly used
      treatment modalities for chronic tendon disorders, there is an obvious lack of
      good trials defining the indications for and efficacy of such injections, and
      subsequently, many of the recommendations for the use of local corticosteroid
      injections do not rely on sound scientific basis. Thus, there is an obvious need
      for high-quality basic science studies and controlled clinical trials in
      examining the effects corticosteroids on various tendon disorders.

PMID- 12512407
TI  - Joint distraction as an alternative for the treatment of osteoarthritis.
AB  - Irrespective of underlying mechanisms, the long-term efficacy of joint
      distraction in the treatment of severe ankle osteoarthritis at young age
      validates the concept of joint distraction in the treatment of osteoarthritis.
      Therefore, joint distraction in the case of severe ankle osteoarthritis may be a
      treatment of choice. This opens the possibility to study joint distraction as a
      treatment for other joints. Because knee osteoarthritis is much more common, it
      is a much greater social and economic problem. Beneficial effects of joint
      distraction in the case of ankle osteoarthritis, and specifically in the
      treatment of more common forms of osteoarthritis such as severe knee and hip
      osteoarthritis, may therefore have a great impact, especially in view of the
      increasing age of our population.

PMID- 12512408
TI  - Syndesmosis injuries in athletes.
AB  - The key to syndesmosis injuries is early recognition of the injury pattern and
      appropriate treatment. The clinician must be wary of the ankle sprain that is
      slow to heal. Radiographic criteria should be examined closely when considering
      the diagnosis; if surgery is warranted, attention to the health of the soft
      tissue envelope is key. Late repairs or reconstructions never have as favorable
      an outcome as the properly repaired acute injury. Postoperative rehabilitation
      should be monitored closely and care should be taken to avoid early return to
      activity that could result in reinjury or damage to the surgical repair or
      reconstruction.

PMID- 12512409
TI  - Syndesmosis injuries: acute, chronic, new techniques for failed management.
AB  - A syndesmotic injury occurs through tearing, rupture, or bony avulsion of the
      syndesmotic ligament complex. The syndesmotic ligament complex consists of the
      anterior tibiofibular, the posterior tibiofibular, the transverse tibiofibular
      and the interosseous ligaments. Without these ligamentous restraints the distal
      tibiofibular joint (DTFJ) widens and can result in an asymmetric ankle mortise.
      Many cadaveric studies have been performed to evaluate the force required and
      amount of DTFJ displacement with progressive sectioning of the syndesmotic
      ligaments.

PMID- 12512410
TI  - Thermal-assisted capsular modification for functional ankle instability.
AB  - Chronic symptoms following lateral ankle sprain occasionally requires surgical
      intervention. Many options are available including thermal assisted capsular
      modification. The authors review the history of thermal modification of tissues,
      the indication for use in the ankle and report their experience with a
      consecutive case series over a one year period.

PMID- 12512411
TI  - Subtalar instability. Etiology, diagnosis, and management.
AB  - Subtalar instability is an evolving disorder that seems to cause a portion of
      chronic hindfoot instability. It can be seen as an isolated problem, or more
      commonly, in combination with ankle instability. There seems to be many injury
      mechanisms, most of which seem to involve supination of the hindfoot, and all
      seem to attenuate the lateral ligaments of the ankle and subtalar joints. As the
      condition progresses, and additional sprains occur as a result of the alteration
      in subtalar joint mechanics, the remaining ligaments become attenuated. There are
      many methods described to diagnose subtalar instability, but no conclusive test
      has been devised. Thus, the diagnosis must be inferred from an accurate history,
      physical examination, conferring radiographic studies, and failure of
      nonoperative management (often, for ankle instability). As with other hindfoot
      injuries, many patients improve with conservative measures. These measures are
      early (ice and immobilization) and late (bracing and proprioceptive training).
      When patients do not improve or cannot tolerate bracing, recent studies have
      shown there is a role for ligamentous reconstruction. Most procedures attempt to
      recreate the lateral ligament structures, including the calcaneofibular, the
      cervical, and the interosseous talocalcaneal ligaments, which seem to have the
      best stabilizing effect on the hindfoot. With the advent of newer procedures and
      more aggressive surgical management, there may be a role for early anatomic
      repair and rehabilitation.

PMID- 12512412
TI  - Surgical repair of acute Achilles tendon rupture using a "mini-open" technique.
AB  - For active patients, surgery is usually the preferred treatment for an acute
      Achilles tendon rupture. Classical open techniques require a long tendon
      exposure, which can result in damage to its blood supply and gliding structures.
      Adhesions may form, which impair the final functional result. Closed surgical
      techniques do not allow for a perfect adaptation of the tendon stumps and have a
      higher rate of rerupture. The "mini-open" technique has advantages over both of
      these techniques. Percutaneously introduced threads prevent adhesions along the
      tendon. The rupture is exposed through a minimal incision and is carefully
      sutured with fine threads to allow a direct healing process without the formation
      of intermediate scar tissue. The minimally invasive approach and the introduction
      of percutaneous threads considerably reduce the time spent in surgery. An
      aggressive rehabilitation program can be initiated 1 week after surgery and
      allows good early functional results.

PMID- 12512413
TI  - Osteoarticular grafts in the treatment of OCD of the talus: mosaicplasty versus
      autologous chondrocyte transplantation.
AB  - Further advancements in articular cartilage transplantation require an
      understanding of the anatomy, physiology, biomaterials, biology, and cartilage
      engineering that are fundamental for better results in joint arthroplasty and
      cartilage repair. Currently, efforts to induce healing and regeneration of
      cartilage are being directed toward enhancing the natural potential of cartilage
      to replace the damaged tissue with cells that can generate cartilage.
      Mosaicplasty and ACT are carried out in the same way, have similar therapeutic
      indications, and have been demonstrated capable of reconstructing hyaline
      cartilage with similar clinical results. ACT is the most recent technique and, in
      the authors' opinion, is preferable in that it is less invasive at the donor site
      and gives better histologic results because of the reconstruction of a continuous
      cartilage sheath compared with that achieved by mosaicplasty. Furthermore, with
      this technique, it is possible to forecast the possibility of improvement owing
      to further technical and biologic advancements. The authors are currently
      experimenting with the use of adhesive patches with substitution of the
      periosteum, resulting in less morbidity. The use of growth factors and new tissue
      engineering techniques in the future would simplify the methodology, rendering it
      less invasive and more effective.

PMID- 12512414
TI  - Approach alternatives for treatment of osteochondral lesions of the talus.
AB  - Osteochondral lesions of the talus are common injuries, especially in the
      athletic population. Although multiple etiologies exist, lateral lesions have a
      higher incidence of association with a specific traumatic event. It has been
      postulated that lateral lesions are produced when the anterolateral aspect of the
      talar dome impacts the fibula on application of an inversion or dorsiflexion
      stress to the ankle [2]. There is general agreement that surgery should be
      performed only in symptomatic cases, as osteochondral lesions of the talar dome
      show little tendency to progression and do not seem to lead to osteoarthritis
      [10,42]. Appropriate preoperative imaging is extremely important. Standard
      radiographs of the ankle supplemented with lateral plantar flexion and
      dorsiflexion views and CT or Mr imaging can be helpful in evaluating the size,
      depth, and exact location of the lesion. This information is essential in
      planning the appropriate surgical procedure. Although many stage I and II lesions
      respond well to conservative therapy and a period of immobilization, some higher
      grade lesions (stage III and IV) eventually require surgical intervention. Most
      lesions can be approached arthroscopically. Many arthroscopic procedures have
      been shown to be successful, including debridement with abrasion chondroplasty,
      subchondral drilling, and microfracture [18-20]. But certain larger or refractory
      lesions may require an open approach to the ankle joint to restore the articular
      cartilage. Most lateral lesions have an anterior location and are easily
      accessible through a standard anterolateral approach. Most medial lesions are
      located on the posterior talar dome, and a medial malleolar osteotomy is usually
      required. Osteotomies, in particular of the medial malleolus, should be
      approached carefully. The possible complications of nonunion and malunion can
      lead to progressive arthritis of the ankle joint.

PMID- 12512415
TI  - Adolescent osteochondral lesion of the talus. Ankle arthroscopy in pediatric
      patients.
AB  - Osteochondral lesions of the talus can be difficult to diagnose and can result in
      a significant functional limitation in young, active patients. New imaging
      modalities have improved the diagnosis and staging of these lesions. In general,
      nonoperative treatment results in poorer outcomes compared with operative
      treatment, and arthroscopic treatment has results similar to open treatment.
      Although the literature is limited, the treatment of adolescents results in
      outcomes similar to the adult population.

PMID- 12512416
TI  - [Progress in the study on tissue culture of Dendrobium].

PMID- 12512417
TI  - [Evaluation on antiendotoxic action and antiviral action in vitro of tetraploid
      Isatis indigotica].
AB  - OBJECTIVE: To evaluate the pharmacological effect of tetraploid Isatis indigotica
      Fort. METHODS: Comparing these actions of tetraploid I. indigotica with those of
      the diploid parent. RESULTS: These actions of tetraploid I. indigotica were
      obviously stronger than those of the diploid parent. The pharmacological effect
      of leaves was greater than that of roots with identical ploidy. CONCLUSION:
      Tetraploid I. indigotica is a new line of better quality, deserving to be
      exploited and utilized on a large scale.

PMID- 12512418
TI  - [Distinguish of the original fungi of the Chinese traditional medicine, hongqu
      with gas chromatography fuzzy clustering analytical method].
AB  - OBJECTIVE: To establish a gas chromatography fuzzy clustering analytical method
      for classifying of origin fungi of the Chinese traditional medicine, Hongqu.
      METHODS: The volatile and nonvolatile components of 7 ordinary species of
      Monascus including M. aurantiacus Lee, etc. were analyzed by capillary gas
      chromatog raphy using FID: Inlet temperature 280 degrees C, detector temperature
      280 degrees C, temperature program 130 degrees C, 5 min-->10 degrees C.min-1-
      >200 degrees C, 10 min. RESULTS: In the peak number and contents of volatile and
      nonvolatile components of Monascus exist obviously differences through which
      Monascus can be distinguished easily by the main fingerprint peaks within 20
      minutes. CONCLUSION: The capillary gas chromatography fuzzy clustering analytical
      method is useful to the identification of Monascus fungi.

PMID- 12512419
TI  - [Pharmacognostical identification of antelope horn(Cornu Saigae Tataricae) and
      its adulterants].
AB  - OBJECTIVE: To provide appropriate information and scientific basis for
      identifying antelope horn (Saiga tatarica) contained in traditional Chinese
      patent medicines, and formulate relevant quality criteria through experiments.
      METHOD: Conducting comparative identification of macroscopic and microscopic
      characteristics of antelope horn(Saige tatarica) and its adulterants (Procapra
      gutturosa, Pantholops hodgsoni, Ovis ammon and Capra hircus) and giving a
      comparative table and an indented key to the main characteristics. RESULT AND
      CONCLUSION: There are remarkable differences between the authentic product and
      adulterants in both macroscopic and microscopic characteristics.

PMID- 12512420
TI  - [Isolation and biological activity of mycorrhizal fungi from Dendrobium candidum
      and D. nobile].
AB  - OBJECTIVE: To isolate the mycorrhizal fungi from the roots of wild Dendribium
      candidum and D. nobile collected from Yunnan and Sichuan provinces and determine
      their biological activities. METHOD: The isolation was completed using solidified
      potato dextrose agar (PDA, Difco) of plates and the biological activities were
      tested by means of symbiotic germination of fungus-seedlings. RESULTS: 25 Species
      of mycorrhizal fungi were obtained and most of them belong to Basidiomycotina and
      Deuteromycotina. The preliminary biological activity test has shown that of these
      fungi 5 species help promote the seed germination of D. candidun, 7 species can
      establish the symbiotical relationship with seedlings of D. candium and D.
      nobile, and 3 species can stimulate the growth of seedlings of the two medicinal
      plants. CONCLUSION: Isolation and screening of fungi helpful to the growth and
      development of Dendrobium is important in the production of the herb.

PMID- 12512421
TI  - [Effect of gradient magnetic field on growth of stem pearls of Dioscorea opposita
      during seedling stage].
AB  - OBJECTIVE: To probe into the bioeffect of gradient magnetic field on the growth
      and development of medicinal plants. METHODS: Gradient magnetic field with
      transmission belt was applied to treat the stem pearis of Dioscorea opposita
      before sowing and an evaluation of the pearl growth during the seedling stage was
      made. RESULT: Treated with twice gradient magnetic field, the stem pearls grew
      the best in the seedling stage. Compared with the control, the rate of emergence
      increased by 38.60%, root number increased by 8%, and the average root length
      increased by 2.62 cm. By F Test, the average root length was F = 19.98, F0.05 =
      6.94 and F0.01 = 18.00. CONCLUSION: Proper magnetic field intensities can promote
      the growth of medicinal plants.

PMID- 12512422
TI  - [Studies on chemical constituents of Erythrina arborescens Roxb].
AB  - OBJECTIVE: To study the chemical constitutes in Erythrina arborescens. METHOD:
      Various chromatographic techniques were used to isolate and purify the
      constituents. The structures were elucidated by spectral analysis and chemical
      evidence. RESULT: Six compounds were isolated from the plant and identified as
      alpinumisoflavone, wighteone, daidzein, genistein, vittadinoside and
      stigmasterol. CONCLUSION: All these compounds were isolated from the plant for
      the first time.

PMID- 12512423
TI  - [Chemical constituents from Eremurus chinensis Fedtsch].
AB  - OBJECTIVE: To investigate the chemical constituents from the herb Eremurus
      chinensis. METHOD: The chemical constituents were extracted with solvent and
      separated with column chromatography. RESULT: The structures were identified as
      chrysophanol 8-Me ether, aloesaponol III, daucosterol and beta-sitosterol.
      CONCLUSION: These compounds were separated from genus Eremurus first time.

PMID- 12512424
TI  - [Determination of furostanol saponins in Bulbus Allii Macroste].
AB  - OBJECTIVE: To establish an Ehrlich reaction-colorimetry method for determining
      furostanol saponins in Bulbus Allii Macroste. METHOD: Based on the coloration
      reaction between furostanol saponins and p-dimethylaminobenzaldehyde, the UV
      detection wavelength used was 515 nm, and the optimum conditions were selected on
      homogeneous design principle. RESULT: The standard curve of macrostemonoside G
      was linear in the concentration range of 0.1975-0.9880 mg.ml-1. The average
      recovery was 97.7% (RSD = 3.65%). CONCLUSION: The method is rapid, accurate and
      easy to operate.

PMID- 12512425
TI  - [A study on quality standard for herba cistanches].
AB  - OBJECTIVE: To establish the quality standard for Herba Cistanches. METHOD: A
      qualitative identification method by TLC was established for five kinds of active
      components(acteoside, echinacoside, cistanoside A, betaine and mannitol) and RP
      HPLC was used to quantify the acteoside contents. RESULTS: Qualitative and
      quantitative analyses were carried out for fourteen kinds of Herba Cistanches and
      eleven kinds of Yinpian. This method is accurate, reliable and of good
      separability and reproducibility. CONCLUSION: This method can be applied as
      standard for the quality control of cistanche deserticola.

PMID- 12512426
TI  - [Recovery effect of cardiomyopeptidin fractions and fraction addition on cardiac
      muscle cells in rats damaged by adriamycin].
AB  - OBJECTIVE: To investigate the recovery effect of cardiomyopeptidin fractions and
      fraction addition on the cardiac muscle cells in rats damaged by adriamycin.
      METHODS: Observing the activity of the succinic dehydrogenase which is at
      mitochondrion in the cells damaged by adriamycin with MTT. RESULTS: Five
      fractions have all promoted the activating effect of the enzyme, the action of PI
      being higher than the others. Fraction addition has also promoted the activating
      effect of the enzyme, but without additive effect. CONCLUSION: The recovery
      effect of cardimyopeptidin depends on the interplay among the fractions.

PMID- 12512427
TI  - [Effect of motherwort herb on the myoelectric activity of uterus in rats].
AB  - OBJECTIVE: To investigate the effect of motherwort herb on the myoelectric
      activity of uterus in rats. METHOD: A pair of bipolar Ag-AgCl electrode was
      implanted on the serosal surface of the uterus in rats, motherwort herb was
      injected intra-abdominal cavity in rats in dose of 0.1 ml, 0.2 ml and 0.4 ml
      respectively, and the changes of uterine myoelectric activity were observed.
      RESULT: Motherwort herb significantly increased the frequency and average
      amplitude of uterus slow waves of in rats. The frequency and maximum amplitude of
      single waves also obviously increased. The time course of outbreak waves was
      prolonged, the series intervals were reduced and the maximum amplitude in each
      outbreak was increased. CONCLUSION: The exciting effect of motherwort herb on the
      uterine smooth muscle may have something to do with the alteration of the ion
      concentration in relation to myoelectric activity, resulting in the increase of
      myoelectric activity of pacesetter cells as well as in the acceleration of
      depolarization of spike activity.

PMID- 12512428
TI  - [Studies on senility retarding effect of qiangshengye liquid].
AB  - OBJECTIVE: To observe the effect of Qiangshengye liquid on senility retarding in
      rats. METHODS: The liquid was orally administrated to rats at doses of 3.3 g.kg-1
      and 6.6 g.kg-1, and after Twenty-one days the activity of superoxide dismutase
      (SOD) in red blood cells and lipid peroxide(LPO) in plasma and in liver were
      examined respectively by spectrophotometry. Fluorescence polarization was used to
      evaluate the fluidity of erythrocyte membrane. In addition the anti-fatigue
      effect of the liquid in mice was detected. RESULTS: The liquid can significantly
      increase the activity of SOD(P < 0.05) in red blood cells and decrease the
      contents of LPO in plasma (P < 0.05) and in liver(P < 0.01). The fluidity of
      erythrocyte membrane was also improved (P < 0.05). CONCLUSION: Qiangshengye
      liquid can antagonize lipid peroxidation and therefore may be used for anti
      fatigue and senility retarding purposes.

PMID- 12512429
TI  - [Influence of monkshood root-peony root combination on inflamation-induced agents
      and free radicals].
AB  - OBJECTIVE: To find out the effect of monkshood root and peony root on
      inflammation-induced agents and free radicals when used separately and in
      combination. METHOD: Two drugs were made into decoctions separately and in
      combination, i.p., qd, for 7 d, red blood cell SOD and serum LPO were analysed
      and the anti-inflammatory actions were observed. RESULTS: In an experimental rat
      model with inflamed paw edema induced by carrageenin or formaldehyde and in a
      mouse model with ear swelling induced by xylene, the anti-inflammatory effect
      appeared stronger when the two drugs were used in combination, especially in
      comparison with the use of monkshood root alone. The exudation of blood
      capillaries and the contents of inflammation medium PGE2 were lowered; The
      activity of SOD extracted from rat or mouse red blood cells was enhanced, and the
      serum LPO, which was high in level when monkshood root was used alone, could be
      declined when the two drugs were used in combination. CONCLUSION: The drug
      combination is more effective in inhibiting inflammation and scavenging free
      radicals.

PMID- 12512430
TI  - [A review of development of pharmacognosy].
AB  - OBJECTIVE: To Review the development of pharmacognosy in China. METHODS: Based on
      relevant materials. RESULTS: The characteristics of the development of
      pharmacognosy in China have been summarized. CONCLUSION: With the passage of
      time, the science of pharmacognosy will take up a new scientific connotation and
      enter a new developing stage which may be called "The Period of Natural
      Pharmacognosy".

PMID- 12512431
TI  - [Resources distribution and pharamacognostic identification of Centella asiatica
      (L.) urban produced in China].
AB  - OBJECTIVE: To investigate the resources distribution and morphological histology
      of Centella asiatica distributed in China, and offer evidences for exploiting the
      plant resources and drafting the quality standards. METHOD: Sample collection,
      document investigation and microscopic section observation. RESULT: A table of
      resources distribution was worked out, the medicinal properties and the
      microscopic characteristics of the stem, leaf and stipe were described.
      CONCLUSION: This study supports the viewpoint of Urban and can be used as a
      reference for the quality standard of Centella asiation.

PMID- 12512432
TI  - [X-ray diffraction Fourier pattern analysis of natural caculus bovis].
AB  - OBJECTIVE: To set up a method for analyzing and distinguishing all the chemical
      components in natural Caoulus Bovis. METHOD: Powder X-ray diffraction analyses
      was used to analyze four samples of natural Caculus Bovis, and the X-ray
      diffraction Fourier pattern was obtained for distinguishing natural Caculus
      Bovis. RESULT AND CONCLUSION: The method can be used for distinguishing animal
      medicinal materials.

PMID- 12512433
TI  - [Comparison of ITS sequences between wild ginseng DNA and garden ginseng DNA].
AB  - OBJECTIVE: To compare the genetic differences between wild ginseng and garden
      ginseng (Panax ginseng). METHOD: The sequences of ITS1 and ITS2 of wild ginsengs
      were determined on LKB DNA sequencing station through Si-liver Sequence DNA
      Sequencing System. The sequencies were aligned with DNA SIS software. RESULTS AND
      CONCLUSION: The ITS1 and ITS2 of Panax were 220-221 and 222-224 bases in length
      respectively. In Panax ginsehg, the seqences of ITS1 were very stable, but ITS2
      were changeable. The ITS2 sequences of No. 87 and No. 110 of the wild ginseng
      collected from Fusong Heilongjiang (China) were exactly the same as those of No.
      U41680(Jun Wen) and No. U41682(Jun Wen) of garden ginseng collected from
      Heilongjiang Province (China) and Korea respectively, but different from those of
      No. U41681(Jun Wen) from Hubei Province (China) in three bases (447, 449, 450)
      The result implies that the cultivated ginsengs may have been introduced from two
      different populations of the wild ginseng.

PMID- 12512434
TI  - [Chemical weed control of medicinal plant Bupleurum falcatum L].
AB  - OBJECTIVE: To select low-residue herbicide for cultivation of Bupleurum falcatum.
      METHOD: Probing the effect of various kinds of herbicide on the budding, growth
      and yield of B. falcatum both in laboratory and in the fields. RESULT AND
      CONCLUSION: Haloxyfop acts slightly on the growth of B. falcarum, but effectively
      kills weeds of many kinds. Butralin is a good herbicide for Gramineae.

PMID- 12512435
TI  - [Determination of major components in liuyingwan pills by supercritical fluid
      extraction(SFE)].
AB  - OBJECTIVE: On the basis of SFE and CGC to establish a method for the qualitative
      and quantitative analysis of major components in Liuyingwan pills. METHOD:
      Orthogonal design and variance analysis were used to optimize the four variables
      (temperature, pressure, volume of modifier and static extraction time) of SFE,
      and the quantification was completed by CGC. RESULT: The optimized conditions are
      as follows: pressure 48.2 MPa, temperature 60 degrees C, 0.2 ml ethyl acetate as
      modifier and static extraction 10 min. The recoveries of borneol and eugenol are
      101.93% (RSD 1.56%) and 98.43% (RSD 2.26%) respectively. CONCLUSION: Compared
      with conventional methods, SFE is rapid, convenient and accurate in determining
      borneol and eugenol.

PMID- 12512436
TI  - [Studies on the flavonol glycosides from the seeds of Vaccaria segetalis].
AB  - OBJECTIVE: To study the chemical constituents of the seeds of Vaccaria segetalis.
      METHOD: Chromatography and spectral analysis were used to isolate the
      constituents and elucidate their structure. RESULT: Three compounds were isolated
      from alcohol extract of the seeds of V. segetalis, and identified as apigenin-6-C
      arabinosylglucoside(1), apigenin-6-C-glucosylglucoside(2), vaccarin(3).
      CONCLUSION: Compound 1 and 2 were isolated from the seeds of this plant for the
      first time.

PMID- 12512437
TI  - [Studies on chemical constituents of Peucedanum medium Dunn var. garcile Dunn ex
      Shan at Sheh].
AB  - OBJECTIVE: To study the chemical constitutents in Peucedanum medium var. gracile
      distributed in Guangxi. METHOD: Chromatography and spectral analysis were used to
      isolated and elucidate the constituents. RESULT: Eight compounds were isolated
      from the root of P. medium var. gracile and elucidated as isoimperatorin,
      phellopterin, bergapten, oxypeucedanin hydrate, byakangelicin beta-sitosterol,
      hamaudol and mannitol. CONCLUSION: Seven compounds were obtained from this plant
      for the first time.

PMID- 12512438
TI  - [Studies on chemical components of Gentiana tizuensis Franch. (I)].
AB  - OBJECTIVE: To study the chemical components of Gentiana tizuensis distributed in
      Qinghai Province. METHOD: Chromatography and spectral analyses were used to
      isolate the constituents and elucidate their structure. RESULT: Four compounds
      were isolated and identified as uvaol, L-(+)-l-O-methyl-myo-inositol, ursolic
      acid,beta-sitosterol. CONCLUSION: All these components were obtained from the
      plant for the first time.

PMID- 12512439
TI  - [Determination of protocatechuic acid in Blumea riparia (Bl.) DC. by RP-HPLC].
AB  - OBJECTIVE: To determine the content of protocatechuic acid in Blumea riparia by
      RP-HPLC. METHOD: mu-Bondapak C18 column was used, mobile phase consisted of
      methanol-water-glacial acetic acid(19:80:1) and detection was performed at UV 260
      nm. RESULT: The standard curve was linear in the range of 3.31-41.8 micrograms.ml
      1. The correlation coefficient was 0.9999. The average recovery rate and RSD were
      98.05% and 1.94% (n = 6) respectively. CONCLUSION: The method provides scientific
      indexes for quality control of riparia.

PMID- 12512440
TI  - [Ocimun oil analysis by GC].
AB  - OBJECTIVE: To establish GC methods for determining eugenol in Ocimun oil. METHOD:
      The determination was effected by GC method, using Chromosorb WAW with 10% PEG
      20M as the stationary phase and column temperature at 200 degrees C. RESULT: The
      calibration curve was linear within the range of 2-10 mg.ml-1 of eugenol. The
      average recovery and relative standard deviation were 101.24% and 0.79%
      respectively. CONCLUSION: The method is simple, accurate, sensitive and free from
      outside interference.

PMID- 12512441
TI  - [Effect of extract from overground part of Tripterygium wilfordii Hook. f. on
      Masugi nephritis in rabbits].
AB  - OBJECTIVE: To observe the effect of extract from overground part of Trpterygium
      wilfordii on Masugi nephritis in rabbits. METHOD: Masugi nephritis was made by
      giving i.v. the rabbit an injection of sheep antirabbit serum. RESULT: The
      extract could effectively inhibit the increase of uric protein, serum BUN,
      creatinine and glomerulus cells in rabbits. CONCLUSION: The extract from
      overground part of Tripterygium wilfordii has better curative effect on Masugi
      nephritis in rabbits.

PMID- 12512442
TI  - [A pharmacological study on suppository for anti-prostatis].
AB  - OBJECTIVE: To approach the pharmacological mechanism of the suppository for anti
      prostatis (SAP). METHOD: Investigating the inflammation of prostate in rat models
      with bacterial and nonbacterial prostatis induced by colonbacillus and "Xiao Zhi
      Ling", as well as the change of rheology in the rat model with acute blood
      stasis. Several tests on anti-inflammation, analgesia and bacteriostasis were
      conducted. RESULT AND CONCLUSION: SAP could restrain the inflammation of prostate
      and resume its secretion obviously. It is very effective for anti-inflammation,
      analgesia and bacteriostasis, and also helps improve the change of theology in
      rats with blood stasis.

PMID- 12512443
TI  - [Contents of general flavonoides in Epimedium acuminatum Franch. and its
      differently-processed products].
AB  - OBJECTIVE: Determining and comparing the contents of general flavonoides in four
      kinds of differently-processed products of Epimedium acuminatum. METHOD:
      Determining the contents by ultraviolet spectrophotometry. RESULT: The contents
      were found in the following seguence: unprocessed product, clearly-fried product,
      alcohol-broiled product, salt-broiled product, sheep-fat-broiled product. The
      average recovery rate was 96.01%, with a 0.74% RSD(n = 5). CONCLUSION: Heating
      causes the contents of general flavonoides in the processed products to decrease.
      These processed products are still often used in clinical treatment, for the
      reason that the adjuvant features certain coordinating and promoting functions.
      The study is to be pursued further.

PMID- 12512444
TI  - [Identification of turtle shell, tortoise plastron and their counterfeit
      products].
AB  - OBJECTIVE: To identify the commercial Chinese medicines turtle shell and tortoise
      plastron. METHOD: Morphological identification and differential thermal analysis
      (DTA). RESULT: 2 kinds of counterfeit turtle shell and 3 kinds of counterfeit
      tortoise plastron were found, and their morphological and DTA identification
      features were proposed. CONCLUSION: Sea turtle shells presently on the market are
      sham commodities of turtle shell, which derive from Lissemys punctata and
      Pelochelys bibroni indigenous to south Asia, while plastrons of Ocadia sinensis,
      Chelonia mydas and Lepidochelys olivacea are counterfeit products of tortoise
      plastron. Turtle shells, tortoise plastrons and their counterfeit products may be
      exactly distinguished by morphological and DTA features.

PMID- 12512445
TI  - [Studies on separation and identification of Rhizoma coptidis brugs based on
      microemulsion thin-layer chromatography].
AB  - OBJECTIVE: To investigate the use of microemulsion TLC for the separation and
      identification of Rhizoma Coptidis drugs. METHOD: Thirteen Rhizoma Coptidis drugs
      were separated and identified with six kinds of SDS/n-C4H9OH/n-C7H16/H2O
      microemulsions as mobile phase on polyamide film. Effects of microemulsions on
      separation were investigated. RESULTS: The best mobile phase was the O/W
      microemulsion(containing 75% water). Compared with general mobile phases, the
      separation and detection could be improved and the test conditions were more
      tolerant. CONCLUSION: This new method is simple, accurate and efficient for the
      separation and identification of Rhizoma Coptidis drugs.

PMID- 12512446
TI  - [Effect of storage methods on breaking seed dormancy of Trollius chinensis Bge].
AB  - OBJECTIVE: Exploring the best seed storage method for Trollius chinensis. METHOD:
      Different temperatures were applied to the seed storage in wet sand and dry sand,
      and the embryo-endosperm ratio and germination rate were inspected. RESULT: The
      dormancy of T. chinensis seeds could only be broken in lower temperatures. The
      newly collected seeds set out to germinate after 75 days of storage at 5-6
      degrees C when the embryo-endosperm ratio reached 47%, and the time of seed
      germination varied with the length of storage time before low-temperature
      treatment. CONCLUSION: The best storage method for the seed of T. chinensis is
      keeping it in dry for 6-8 months with an additional 1 month of low-temperature
      treatment to follow.

PMID- 12512447
TI  - [Effects of culture conditions on callus growth and taxol formation of Taxus
      yunnanensis Cheng et L.K.Fu].
AB  - OBJECTIVE: To seek culture conditions suitable for the callus growth and taxol
      formation of Taxus yunnanensis. METHOD: Determining the growth index and taxol
      content in the callus cultured under different illumination conditions or on
      different media. RESULTS AND CONCLUSION: Darkness, the combination of 0.1 mg.L
      1BAP and 2,4-D 1.0 mg.L-1, and B5, DCR or 6,7-V basal medium were favorable for
      the callus growth and taxol formation of Taxus yunnanensis; high NO3-
      concentration in the medium promoted callus growth, and high NH4+ concentration
      greatly inhibited callus growth, but dramatically increased taxol content.

PMID- 12512448
TI  - [Studies permeation of puerarin and its phospholipid complex through mouse skin
      in vitro].
AB  - OBJECTIVE: To investigate the skin permeation of puerarin and its phospholipid
      complex and compare the differences between their permeation rates and cumulative
      permeation amounts. METHOD: Performing a test of permeation through the mouse
      skin in vitro in an improved Franz diffusion cell. RESULT: The cumulative
      permeation amount of phospholipid complex was higher than that of puerarin in the
      first hour and then increased slowly, meanwhile the permeation rate of puerarin
      rose higher than that of the complex. CONCLUSION: Phospholipid complex of
      puerarin can permeate through the mouse skin rapidly up to a certain amount in a
      short time, then begins to release drug slowly and lastingly.

PMID- 12512449
TI  - [Studies on flavonoids from leave of Eucommia ulmoides Oliv].
AB  - OBJECTIVE: To separate the constituents from Eucommia ulmoides. METHOD: The
      constituents were separated by the repeated chromatography and identified by
      spectral methods. RESULT: The seven compounds were obtained, which were
      kaempferol(1), quercetin(2), astragalin(3), hirsutin(4), rutin(5), 3,4
      dihydrobenzonic acid(6), ethyl glucopyranoside(7). CONCLUSION: Compounds 3-7 were
      obtained from leaves of E. ulmoides for the first time.

PMID- 12512450
TI  - [Studies on chemical constitutents in seeds of Allium tuberosum Rottl].
AB  - OBJECTIVE: To study the chemical constituents in the seed of Allium tuberosum.
      METHOD: Chromatography and spectral analysis were used to isolate the
      constituents and elucidate their structures. RESULT: Five compounds were isolated
      from the alcohol extracts of the seeds and identified as nicotianoside C, (22S)
      cholest-5-ene-1 beta, 3 beta, 16 beta, 22-tetrol-1-O-alpha-L-rhamnopyranosyl-16-O
      beta-D-glucopyranoside, daucosterol, adenosine and thymidine. CONCLUSION: All the
      compounds were isolated from the seed of this plant for the first time.

PMID- 12512451
TI  - [Extraction and separation of antitumor components from Ganoderma lucidum (Leyss.
      ex Fr.) Karst].
AB  - OBJECTIVE: To examine the variation of alcohol extraction rates of Ganoderma
      lucidum spores with different rates of wall-wrack, and analyze the antitumor
      components of alcohol extract by chromatography. METHOD: The G. lucidum spores
      were soaked and extracted with absolute alcohol. The alcohol extract was
      chromatographed on a silica gel column and HPLC in proper order, and the
      antitumor activity of every eluted fraction was represented by its cytotoxicity
      towards Hela cells. RESULT: Extraction rates 5%, 25% and 33% corresponded to wall
      wrack rates 0%, 60%-80% and 99% respectively. The alcohol extract from spores
      with the highest wall-wrack rate was chromatographed on a silica gel column,
      eluting successfully with CHCl3, EtOAc and CH3OH in order. The CHCl3 fraction had
      not any antitumor activity, while this activity of CH3OH fraction was 34 times
      greater than that of EtOAc fraction. HPLC analysis found out that two
      mixtures(II1 and II3) possess significant antitumor activity in vitro.
      CONCLUSION: The weight of alcohol extract from spores with wall-wrack was far
      greater than that of spores without. The antitumor components of G. lucidum
      spores could be analyzed with methanol-water on a reverse HPLC.

PMID- 12512452
TI  - [Flavonoids from Shuteria pampaninianna Hand.-Mazz].
AB  - OBJECTIVE: To investigate the chemical constituents of the herbs of Shuteria
      pampaninianna. METHOD: Using polyamide columine chromatography and NMR spectra to
      isolate pure flavonods and determine their structures. RESULT: Two flavonoids
      have been isolated from whole plant of S. pampaninianna and identified as
      myricetin(1) and ampelopsin(2) respectively. CONCLUSION: Both 1 and 2 were
      obtained from this plant for the first time.

PMID- 12512453
TI  - [Chemical constituents from Speranskia tuberculata (Bge.) Baill].
AB  - OBJECTIVE: To investigate the chemical constituents from the herb Speranskia
      tuberculata. METHOD: The chemical constituents were extracted with solvent and
      separated with column chromatography. The structures were elucidated by spectral
      analysis. RESULT: Two compounds were isolated from the plant and identified as 18
      hydroxy(-)-manool and beta-sitosterol. CONCLUSION: Both were separated from this
      plant first time.

PMID- 12512454
TI  - [An experimental study on inhibitory effect of xinjierkang granules on virus
      myocarditis].
AB  - OBJECTIVE: To investigate the inhibitory effect of Xinjierkang(XJEK) granules on
      virus myocarditis. METHODS: Using a model mouse of virus myocarditis induced by
      coxsackie virus B3m (CVB3m) and mouse toxic myocarditis induced by adriamycin, a
      model of arrhythmia induced by BaCl2 and CHCl3, a model of inflammation caused by
      egg white and agar, along with a dynamic test of cardiac blood flow and an
      inhibitory test of CVB3m in vitro. RESULTS: XJEK granules are efficacious in
      inhibiting CVB3m both in vitro and in vivo, protecting and curing virus
      myocarditis and toxic myocarditis in mice, reducing mouse death rate, serum level
      of LDH, AST and CK, titer of neutralizing antibodies, virus concentration of
      heart, and improving the abnormal ECG, pathological and ultrastructural damage of
      myocadium. The granules are also good for anti-inflammation, anti-myocardial
      ischemia, anti-arrhythmia, as well as for strengthening myocardiac contraction
      and increasing the serum IgG level. CONCLUSION: Xinjerkang granules possess an
      inhibitory effect on virus myocarditis and toxic myocarditis.

PMID- 12512455
TI  - [A pharmacodynamic research on chromone glucosides of fangfeng].
AB  - OBJECTIVE: To investigate the pharmacological activity of prim-O
      glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol con tained in
      Fangfeng. METHODS: Analgesic, antipyretic and antiinflammatory effects were
      assessed using the models of yeast-induced rat fever, acetic acidinduced
      peritoneal pain thermalpain, and dimethylbenzol-induced mouse ear edema. RESULTS:
      Prim-O-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol could
      reduce the body temperature of rats in a model of yeast-induced fever. Both
      components could decrease the spasm action induced by peritoneal injection of
      acetic acid, increase the pain-threshold in a thermal-pain model, relieve the
      mouse ear edema caused by dimethybenzol and significantly inhibit ADP-induced
      platelet aggregation. CONCLUSION: Prim-O-glucosylcimifugin and 4'-O-beta-D
      glucosyl-5-O-methylvisamminol have significant analgesic, antipyretic, anti
      inflammatory and anti-platelet aggregation actions.

PMID- 12512456
TI  - [Effects of components isolated from Astragalus membranaceus Bunge on cardiac
      function injured by myocardial ischemia reperfusion in rats].
AB  - OBJECTIVE: To investigate the effects of components isolated from Astragalus
      membranaceus on myocardial ischemia reperfusion injury. METHODS: The myocardial
      ischemia reperfusion injury model was created by the left anterior descending
      coronary artery occlusion from the oracotouated rats, and the total saponins,
      total flavonids and astragaloside i.v. isolated from A. membranaceus on
      hemodynamics during acute myocardial ischemia, Na(+)-K(+)-ATPase activity, cAMP
      and malondialdehyede (MDA) contents in the ischemic myocardium were observed.
      RESULTS: The total saponins, total flavonids and astragaloside i.v. attenuated
      the declines of the amplitudes of LVSP and +/- LVdp/dtmax in rat heart injured by
      ischemia reperfusion in vivo, and decreased Na(+)-K(+)-ATPase activity in the
      ischemic myocardium. Otherwise, the total saponins increased the cAMP content and
      the total flavonids decreased the level of MDA production in the ischemic
      myocardium. CONCLUSION: The effects of different components isolated from A.
      membranaceus on protecting the cardiac function in the process of ischemia
      reperfusion may be related to the mechanism of improving energy metabolism,
      scavenging the oxygen free radicals and inhibiting the production of free
      radicals in the ischemic myocardium.

PMID- 12512457
TI  - [Action of fengsuidan granules on experimental anti-oral ulcer].
AB  - OBJECTIVE: To explore the anti-oral ulcer action, anti-inflammatory and analgesic
      effect of Fengsuidan Granules(FSDG). METHODS: FSDG(0.5, 5.0, 10.0 g.kg-1) were
      administered to experimental animals. The oral ulcer in experimental animals was
      effected by means of white staphylococcus (sc) and carbolic acid (buming).
      RESULTS: Such as acetic acid body turning, hot-plate, auricle inflammation by
      dimethylbenzene and foot swelling by egg white were used. CONCLUSION: Following
      certain regularities of dose-effect relationship, FSDG has anti-oral ulcer
      effect, helps reduce and heal the ulcer and works efficaciously in analgesic and
      anti-inflammatory cases.

PMID- 12512458
TI  - [Observation of cell ultrastructuse in suppurative otitis media treated with
      bosneol and application].
AB  - OBJECTIVE: To explore the pharmacological action and optimal concentration of
      borneol in treating suppurative otitis media. METHOD: Aspergillus niger separated
      from the secretion in external auditory canal of the patient and the fungus
      strains kept in the laboratory were used to determine the minimum fungus
      inhibiting concentration (MIC) and minimum fungus killing concentration (MFC) of
      borne. The change of cell ultrastructure after borneol taking effect was observed
      under electron microscope. RESULT: Borneol MIC and MFC turned out to be 5% and
      10% respectively. The cell wall of Aspergillus niger became thicker and blurred
      with vacuoles. In the cytoplasm various materials were found deep dyed and
      agglutinated with many fat drops. The electron density increased and the ridge
      arrangement was in disorder. Some organelles were destroyed, and many areas of
      electron blank appeared. Some cells became warped and deformed and lost their
      original structure. CONCLUSION: Borneol can destroy the structure of fungus
      cells, make fungus dissolve and dieout and thus features a fungus inhibiting and
      killing function. The optimal inhibiting concentration is 5% and killing
      concentration 10%.

PMID- 12512459
TI  - Knowledge for improvement: who will lead the learning?
AB  - If we wish to improve the results of a system, what is needed to help health
      professionals learn about the redesign of that system? To create learning
      experiences that will attract good health professionals, a special blend of
      practical insight and critical thinking is required. To enjoy good standing in
      the academy, these leaders must be able to design, conduct, and disseminate
      knowledge-building activities subject to peer review. This is the story of the
      development of the United States Veteran's Health Administration Quality Scholars
      Program from those who designed and formed it to prepare health professional
      teachers and academics.

PMID- 12512460
TI  - A curriculum for training quality scholars to improve the health and health care
      of veterans and the community at large.
AB  - In 1998, the Veterans Health Administration invested in the creation of the
      Veterans Administration National Quality Scholars Fellowship Program (VAQS) to
      train physicians in new ways to improve the quality of health care. We describe
      the curriculum for this program and the lessons learned from our experience to
      date. The VAQS Fellowship program has developed a core improvement curriculum to
      train postresidency physicians in the scholarship, research, and teaching of the
      improvement of health care. The curriculum covers seven domains of knowledge
      related to improvement: health care as a process; variation and measurement;
      customer/beneficiary knowledge; leading, following, and making changes in health
      care; collaboration; social context and accountability; and developing new,
      locally useful knowledge. We combine specific knowledge about the improvement of
      health care with the use of adult learning strategies, interactive video, and
      development of learner competencies. Our program provides insights for medical
      education to better prepare physicians to participate in and lead the improvement
      of health care.

PMID- 12512461
TI  - Finding the target: getting started with quality of care and health services
      research.
AB  - Choosing a research project and career goal requires planning. This article
      provides advice for the junior investigator on choosing a career path in health
      services research or quality improvement, developing and focusing project ideas,
      and assessing the merit of these choices. By providing specific strategies and
      examples, the authors highlight the importance of conceptual vision, an
      inquisitive perspective, and scientific rigor in both project and career
      development.

PMID- 12512462
TI  - Improving the effectiveness of physician participation in local quality
      improvement efforts.
AB  - The authors present five success factors for medical students, residents, and
      fellows to consider when engaged in quality improvement projects: (1) add value,
      not work; (2) start small and build; (3) move quickly; (4) adapt, innovate, and
      collaborate; (5) produce understandable results. Using examples from the Veterans
      Affairs National Quality Scholars Fellowship Program, they describe how these
      factors were used successfully. While not the only steps to take, these critical
      success factors proved helpful in defining the problem to be addressed, engaging
      leadership, and anticipating the resolution of conflict.

PMID- 12512463
TI  - Anthrax attacks and practice patterns: a learning opportunity for health care
      systems.
AB  - Sudden and unexpected events directly influencing clinical practice patterns are
      uncommon. After the first report of bioterrorism-related anthrax, the authors
      studied retrospectively 13 months of anthrax-related antibiotic prescription
      rates for Veterans Affairs outpatients in one urban area where no cases of
      anthrax were reported. During the 26 days after the first anthrax report, the
      rate of acute respiratory illnesses treated with fluoroquinolones was 62.8 per
      10,000 outpatient visits, an increase of 41 percent over the rate of 44.4
      observed approximately one year earlier (p = 0.058). Acute sociopolitical events
      such as bioterrorist attacks present a unique opportunity to investigate changes
      in health care.

PMID- 12512464
TI  - Applying the theory of constraints in health care: Part 1--The philosophy.
AB  - The imperative to improve both technical and service quality while simultaneously
      reducing costs is quite clear. The Theory of Constraints (TOC) is an emerging
      philosophy that rests on two assumptions: (1) systems thinking and (2) if a
      constraint "is anything that limits a system from achieving higher performance
      versus its goal," then every system must have at least one (and at most no more
      than a few) constraints or limiting factors. A constraint is neither good nor bad
      in itself. Rather, it just is. In fact, recognition of the existence of
      constraints represents an excellent opportunity for improvement because it allows
      one to focus ones efforts in the most productive area--identifying and managing
      the constraints. This is accomplished by using the five focusing steps of TOC:
      (1) identify the system's constraint; (2) decide how to exploit it; (3)
      subordinate/synchronize everything else to the above decisions; (4) elevate the
      system's constraint; and (5) if the constraint has shifted in the above steps, go
      back to step 1. Do not allow inertia to become the system's constraint. TOC also
      refers to a series of tools termed "thinking processes" and the sequence in which
      they are used.

PMID- 12512465
TI  - Baldrige-based quality awards: Veterans Health Administration's 3-year
      experience.
AB  - This article describes the Veterans Health Administration's (VHA's) 3-year
      experience with an internal, Baldrige-based quality award. The authors examined
      scores for Veterans Integrated Service Networks (VISNs), which received site
      visits, variation in year-to-year survey outcomes for repeat applicants, and
      variation in survey team reports for a VISN with multiple surveys. Individual
      VISNs that applied in multiple years had mixed results. Variation in feedback
      reports was not significant. Although some VISNs increased their scores over
      time, there was not measurable, systemwide improvement. Three years may be too
      short a time to significantly affect Baldrige scores in an organization as large
      as VHA.

PMID- 12512466
TI  - Quality improvement as an investment.
AB  - Health care organizations are experiencing increasing internal and external
      pressures to improve the quality of care that they provide. However, there is not
      a framework that can be used to help understand the value of quality improvement
      projects and to prioritize competing projects. By understanding the current
      processes, costs and outcomes of care, enumerating the costs and benefits of
      change, anticipating the timing of the costs and benefits, and performing a
      financial analysis, quality improvement efforts can be evaluated as investments.
      Only by understanding and adapting to the financial environments in which health
      care organizations operate can continuous quality improvement in health care
      succeed.

PMID- 12512467
TI  - Exploring the academic context for quality improvement: a scientific discipline
      in need of a career path.
AB  - Physician training typically occurs in an academic context. We examine whether
      improvement should be a central element in academe--specifically medical school.
      We observe that quality improvement meets the criteria for a discipline, but that
      there are many obstacles to career development in this field. Whether the
      research agenda of quality improvement can be accomplished within centers or
      institutes or whether this discipline needs its own department to ensure the
      nurturing of new faculty is still an open question. What is not open is the
      necessity for a career path in this discipline to exist and flourish.

PMID- 12512468
TI  - The VA National Quality Scholars Fellowship Program: current status, future
      directions.
AB  - The National Quality Scholars Fellowship Program has been highly successful in
      recruiting excellent fellows for training in process improvement and quality
      principles. Opportunities for improvement include improved communication with
      facility personnel and closer alignment with local improvement needs.
      Retention/recruitment of these skilled physicians and creation of a network of
      trained Veterans Affairs (VA) physicians are newly articulated goals.

PMID- 12512469
TI  - [Vasculo-renal disease].
AB  - The kidney as an apo-exocrine organ has two important functions: the control of
      homeostasis and arterial blood pressure. Any pathological disorders witch alters
      the renal blood flow results in two consequences: renovascular hypertension and
      renal insufficiency. Renal revascularization looks for with priority the
      improvement of renal function; the good response and control of hypertension
      shall come after. The goals of this paper is to actualize the sophisticated
      diagnostic methods (Angiography, Eco-Doppler, AngioCT, AngioMR, Angioscopy; and
      the use of contrast potential-mediums), functionality tests (RN and MR with
      Captopril) and management (Percutaneous transluminal angioplasty, simple or
      covered Stents, Embolizations, Occlusive balloons, Fibrinolysis and Trombus
      Aspiration; direct Arterial Surgery and renal Autotransplantation) of different
      renovascular diseases. (Blunt renal injuries, Stenosis, Aneurysms. A-V fistuls,
      Acute Occlusions or arterial and venous, Thrombosis. Nutcraker Syndrome). The
      possibility of the presence of an inverse venous Fraley's Syndrome is presented
      and discussed. CONCLUSIONS: A controversy of the last technical methods are
      established and discussed and a Guideline is recommended for each renal vascular
      disease.

PMID- 12512470
TI  - Pro-GnRH processing.

PMID- 12512471
TI  - Smallpox vaccination--update. 1981.

PMID- 12512472
TI  - Need for recovery in the working population: description and associations with
      fatigue and psychological distress.
AB  - This study examined the concept of need for recovery, that is the need to
      recuperate from work-induced fatigue, experienced after a day of work. The study
      explored the relationship between need for recovery from work, prolonged fatigue,
      and psychological distress in the working population. A cross-sectional study was
      carried out. Data of the Maastricht Cohort Study on fatigue at work were used (n
      = 12,095). Some degree of need for recovery was found in nearly all employees.
      Need for recovery from work was associated with demographic, work-related, and
      health factors. Principal Components Analysis revealed obvious separation between
      need for recovery items and both fatigue items and psychological distress items,
      supporting the notion that need for recovery, fatigue, and psychological distress
      represent different underlying concepts. Although need for recovery, fatigue, and
      psychological distress were frequently comorbid, they also clearly occurred as
      separate entities.

PMID- 12512473
TI  - Nurses, nurses, nurses.  You can't live without them!

PMID- 12512478
TI  - How to use electrical stimulation for wound healing.

PMID- 12512483
TI  - Spotlight on orthopedic nursing.

PMID- 12512484
TI  - Administering medication through a gastrostomy tube.

PMID- 12512485
TI  - How strictly should a patient with C. difficile be isolated?

PMID- 12512493
TI  - Understanding brain death criteria.

PMID- 12512494
TI  - Keeping pulmonary tuberculosis at bay.

PMID- 12512495
TI  - What to do when a temporary pacemaker malfunctions.

PMID- 12512496
TI  - Loaded questions.

PMID- 12512497
TI  - How to treat a migraine.

PMID- 12512500
TI  - When bed isn't a safe haven.

PMID- 12512501
TI  - Myths and facts...about whooping cough.

PMID- 12512502
TI  - Learning about tai chi chuan. Feeling stressed? Give this quiet exercise a try.

PMID- 12512503
TI  - 2001 Distinguished Service Award of the IEEE Ultrasonics, Ferroelectrics, and
      Frequency Control Society. Arthur Ballato. Institute of Electrical and Electronic
      Engineers.

PMID- 12512504
TI  - The effects of IgM-enriched immunoglobulin preparations in patients with severe
      sepsis: another point of view.

PMID- 12512505
TI  - The limitations of observational studies on the treatment of severe sepsis.

PMID- 12512507
TI  - In the middle of the beginning.

PMID- 12512506
TI  - The case of six honest serving men and "hypercuriosis".

PMID- 12512508
TI  - Bibliography.

PMID- 12512509
TI  - Chernobyl: an overlooked aspect?

PMID- 12512510
TI  - Another look at water and ice.

PMID- 12512511
TI  - Smart crows win out.

PMID- 12512512
TI  - HIV-1 subtype C reverse transcriptase and protease genotypes in Zimbabwean
      patients failing antiretroviral therapy.
AB  - HIV-1 drug resistance mutations have been identified and characterized mostly in
      subtype B HIV-1 infection. The extent to which antiretroviral drugs select for
      drug resistance mutations in non-subtype B HIV-1 is not known. We obtained HIV-1
      reverse transcriptase (RT) and protease sequences from 21 Zimbabwean patients
      failing antiretroviral drug therapy. We compared these sequences with 56
      published RT and protease subtype C sequences from untreated patients, 990 RT and
      1140 protease subtype B sequences from treated patients, and 340 RT and 907
      protease subtype B sequences from untreated patients and identified four mutation
      categories of subtype C HIV-1. Seventeen of the 21 patients (81%) had known drug
      resistance mutations. Mutations at 15 RT and 11 protease positions were more
      common in subtype C isolates than in subtype B isolates. HIV-1 subtype C-infected
      individuals receiving antiretroviral therapy develop many of the known subtype B
      drug resistance mutations. Comparison of subtype C RT and protease sequences with
      a large database of subtype B sequences identified subtype C-specific
      polymorphisms and candidate drug resistance mutations.

PMID- 12512514
TI  - Ongoing clinical trials.

PMID- 12512513
TI  - Phylogenetic and phenotypic analysis of HIV type 1 env gp120 in cases of subtype
      C mother-to-child transmission.
AB  - Human immunodeficiency virus type 1 (HIV-1) subtype C constitutes a majority of
      the newly transmitted cases of HIV-1 in many developing countries. There is
      growing evidence suggesting that subtype C viruses may display characteristics
      that make them distinct from subtype B and other subtypes, and such differences
      may affect its transmission and pathogenesis in infected individuals. In this
      study, HIV-1 sequences from the C2-V4 region of the envelope gene were analyzed
      from four infected mother-infant pairs (MIPs) after perinatal transmission in
      Zambia. We found that all viral isolates from four Zambian MIPs were of the
      subtype C HIV-1 subgroup. All tested isolates were macrophage tropic and did not
      infect any tested T cell lines or form syncytia in vitro. In addition, the
      isolates appear to use exclusively the CCR5 coreceptor. Phylogenetic analyses
      clearly indicated two contrasting phylogenetic transmission patterns for the four
      MIPs analyzed in the present study. Three cases displayed a pattern of selective
      transmission of a single or a few variants, and one case was found to transmit
      multiple maternal HIV-1 variants to her infant. The differences in the mode and
      timing of transmission may account for the observed transmission pattern among
      four MIPs.

PMID- 12512515
TI  - Failed ulnar head resection: prevention and treatment.
AB  - Distal ulnar head resections may cause a painful impingement of the distal ulnar
      stump against the radius during loaded forearm rotation. Different soft-tissue
      procedures have been suggested to solve this difficult problem, but none has
      demonstrated clear superiority over the others. The introduction of a variety of
      ulnar head and total radio-ulnar joint prostheses has provided a new method of
      addressing this problem, but there is presently no evidence that these implants
      produce long-lasting results. This paper critically reviews these different
      options, and emphasizes techniques which may help to minimize the risk of
      complications when excision of the ulnar head is unavoidable.

PMID- 12512516
TI  - Retrospective clinical studies.

PMID- 12512517
TI  - The individual health insurance market: researchers, policy makers seek common
      ground on tax credits for the uninsured.
AB  - As policy makers in Washington consider the use of tax credits to encourage
      uninsured Americans to buy health insurance, researchers and policy experts
      debated the merits of the individual health insurance market at a conference
      sponsored by the Center for Studying Health System Change (HSC) and Health
      Affairs. One presenter estimated that the individual market "works acceptably
      well for about 80 percent of potential buyers" but is unlikely to help the
      remaining 20 percent, who suffer from the worst health. Another presenter argued
      that the individual market "is not a good place to target substantial new
      resources aimed at lowering the number of uninsured persons." A proposal that
      intrigued many conference attendees is to have the federal government serve as a
      reinsurer of the individual market "by assuming responsibility for most of the
      costs of people in the highest 2 percent to 3 percent of the national spending
      distribution."

PMID- 12512518
TI  - SCHIP, Medicaid expansions lead to shifts in children's coverage.
AB  - Recent expansions of the State Children's Health Insurance Program (SCHIP) and
      Medicaid have led to significant shifts in insurance coverage for children. New
      findings from the Center for Studying Health System Change (HSC) show that the
      proportion of low-income children who were uninsured dropped from 20.1 percent in
      1997 to 16.1 percent in 2001, a result of significant increases in public program
      coverage. The net effect of these gains in coverage was limited, however, by a
      decline in private insurance coverage (from 47% in 1997 to 42.3% in 2001). The
      drop in private insurance was due, in part, to substitution of public for private
      insurance coverage.

PMID- 12512519
TI  - Environmental biotechnology.

PMID- 12512520
TI  - 2003 buyer's guide.

PMID- 12512521
TI  - [Spatial orientation of the vestibulo-ocular reflex].

PMID- 12512522
TI  - [Development of the aortic baroreflex under conditions of microgravity].

PMID- 12512523
TI  - [Autonomic neuroplasticity in weightlessness].

PMID- 12512524
TI  - [The effects of space environment on differentiation and mutation frequency in
      Dictyostelium discoideum].

PMID- 12512525
TI  - [Comparison of the effects of accelerated heavy ions and X-rays on the
      development of rat brain].

PMID- 12512526
TI  - [Study of DNA damages and repair in human cultured fibroblasts irradiated with
      carbon-ion beam].

PMID- 12512527
TI  - [Effect of gravity on the induction of somatic mutations by radiation in
      Drosophila].

PMID- 12512528
TI  - [Effect of a microgravity environment on Escherichia coli cells damaged by carbon
      ion beams during the Shuttle/Mir Mission no. 6].

PMID- 12512529
TI  - [Space experiments on mini closed ecosystem--results from three flights--(1)
      water, organic compounds, carbon isotopic ratio].

PMID- 12512530
TI  - [Space experiments on mini closed ecosystem--results from three flights--(2)
      microorganisms and plant].

PMID- 12512531
TI  - [Space experiments on mini closed ecosystem--results from three flights--(3)
      animals].

PMID- 12512532
TI  - [Mini ecosystem summary of three flight experiment (4) performance of digital
      video camcorder implemented for mini ecosystem on space station Mir].

PMID- 12512533
TI  - [The effects of space radiation on DNA damage and mutation in plasmid DNA, E.
      coli and human DNA for long-term flight in MIR].

PMID- 12512534
TI  - [MIR experiment for radiation biology effect: rpsL mutation induction in B.
      subtilis spore].

PMID- 12512535
TI  - [Effect of the Mir space flight on induction of the rpsL mutation in the yeast
      Saccharomyces cerevisiae].

PMID- 12512536
TI  - [Rheological properties of the aortic wall of the premature rat bred in space].

PMID- 12512537
TI  - [The effects of microgravity on repair activity of DNA ligase for DNA damage].

PMID- 12512538
TI  - [The effects of microgravity on induced mutation in E. coli and yeast].

PMID- 12512539
TI  - [Postural control of upside-down catfish under the microgravity produced by
      parabolic flight].

PMID- 12512540
TI  - [Response of amphibians to the parabolic aircraft flight].

PMID- 12512541
TI  - [Analysis of a mutant Medaka fish ha--ground and parabolic experiments].

PMID- 12512542
TI  - [Production of the fish better suited for microgravity--ground and parabolic
      experiments].

PMID- 12512543
TI  - [Behavior of Medaka fish and pond skaters together with a large air bubble under
      microgravity].

PMID- 12512544
TI  - [Mechanical environment during parabolic flight of MU-300 jet plane].

PMID- 12512545
TI  - [Gravitaxis of Paramecium: testing the hypotheses by free-fall experiments].

PMID- 12512546
TI  - [Influences of microgravity on protein crystal growth].

PMID- 12512547
TI  - [Inhibition of growth of azuki bean seedlings by hypergravity].

PMID- 12512548
TI  - [Development and operation of cultured cell experiment with TR-IA sounding
      rocket].

PMID- 12512549
TI  - [In relation to ethical issues of the physician's profession, the Hippocratic
      Oath is always quoted].

PMID- 12512550
TI  - Data and information quality strategic plan.
AB  - The Environmental Protection Agency's Strategic Plan was developed in response to
      internal and external concerns about the integrity, consistency, and accuracy of
      EPA's environmental data. This document explains why a Strategic Plan is needed
      and the methodology used in its development, cites Agency models of excellence,
      and presents the six recommendations of EPA's Data and Information Quality
      Strategic Plan.

PMID- 12512551
TI  - Control by quality: proposition of a typology.
AB  - The application of Quality tools and methods in industrial management has always
      had a fundamental impact on the control of production. It influences the behavior
      of the actors concerned, while introducing the necessary notions and
      formalizations, especially for production systems with little or no automation,
      which constitute a large part of the industrial activity. Several quality
      approaches are applied in the workshop and are implemented at the level of the
      control. In this paper, the authors present a typology of the various approaches
      that have successively influenced control, such as statistical process control,
      quality assurance, and continuous improvement. First the authors present a
      parallel between production control and quality organizational structure. They
      note the duality between control, which is aimed at increasing productivity, and
      quality, which aims to satisfy the needs of the customer. They also note the
      hierarchical organizational structure of these two systems of management with, at
      each level, the notion of a feedback loop. This notion is fundamental to any kind
      of decision making. The paper is organized around the operational, tactical, and
      strategic levels, by describing for each level the main methods and tools for
      control by quality. The overview of these tools and methods starts at the
      operational level, with the Statistical Process Control, the Taguchi technique,
      and the "six sigma" approach. On the tactical level, we find a quality system
      approach, with a documented description of the procedures introduced in the firm.
      The management system can refer here to Quality Assurance, Total Productive
      Maintenance, or Management by Total Quality. The formalization through procedures
      of the rules of decision governing the process control enhances the validity of
      these rules. This leads to the enhancement of their reliability and to their
      consolidation. All this counterbalances the human, intrinsically fluctuating,
      behavior of the control operators. Strategic control by quality is then detailed,
      and the two main approaches, the continuous improvement approach and the
      proactive improvement approach, are introduced. Finally, the authors observe that
      at each of the three levels, the continuous process improvement, which is a
      component of Total Quality, becomes an essential preoccupation for the control.
      Ultimately, the recursive utilization of the Deming cycle remains the best
      practice for the control by quality.

PMID- 12512552
TI  - Antioxidant parameters of horses according to age, sex, breed and environment.
AB  - Antioxidant defences interact to form an integrated system. There is no
      comprehensive and uniform view on issues concerning the antioxidant status in
      horses. Therefore, the aim of the present study was to estimate antioxidant
      parameters in horses of different age, sex and breed as well as environment and
      relationship between different antioxidants. Parameters of selected antioxidants
      including superoxide dismutase (SOD), glutathione peroxidase (GSH-px), total
      antioxidant status (TAS), ceruloplasmin (CP), bilirubin, uric acid, zinc, copper
      and selenium were determined in blood of 80 clinically healthy horses.
      Antioxidant parameters significantly varied between horses form different
      environments or different breed and sex. Age of horses had no significant effect
      on antioxidant parameters. Significant correlation coefficients were observed
      between enzymatic and nonenzimatic antioxidants. The nature of the relationship
      between the antioxidant system in horses with respect to environmental factors is
      rather complex and to date only a part of system is known.

PMID- 12512553
TI  - Studies on histogenesis of mixed tumours of the mammary gland in bitches.
AB  - The aim of the study was the immunohistochemical assessment of the reactivity of
      mixed tumours in bitches with special regard to myoepithelial cells and
      cartilage. The materials for study were 20 mixed tumours collected during surgery
      or autopsy. Paraffin-embedded sections were routinely stained with hematoxylin
      and eosin and HID method was also used. Immunohistochemical assays were made
      using the AB-Complex method with the use of monoclonal antibodies against:
      cytokeratin MNF-116, cytokeratin 19, vimentin, actin and S-100 protein. On the
      basis of the reactions, 5 types of myoepithelial origin cells transformed during
      the formation of cartilage cells were diagnosed.

PMID- 12512554
TI  - Investigation on the inhibition of Campylobacter jejuni growth with the
      applications of some preservatives, medicines, herbs and herb preparations.
AB  - The aim of this study was to determine the influence of chosen preservatives,
      medicines, herbs and herb preparations on 39 Campylobacter jejuni strains, which
      were isolated from fresh poultry carcasses. De-Nol and ventrisol were used in the
      original concentration. Propolis, propolan, artecholin and aukalen were of
      pharmacies origin. The rest of substances examined were 10% water solutions. Out
      of 11 substances examined, potassium sorbate, sodium benzoate, De-Nol and
      ventrisol exerted the strongest inhibitory action on Campylobacter jejuni.

PMID- 12512555
TI  - Toxoplasma gondii infection of cats in epizootiological and clinical aspects.
AB  - A total of 200 cats from a south-western region of Poland were tested for
      antibodies to T. gondii. 105 (52.5%) examined cats were seropositive for T.
      gondii. Positive results were found in 16 (50%) out of 30 homeless cats, 33 (55%)
      out of 60 cats kept in shelters, and 56 (51.85%) out of 108 pet cats visiting
      outpatients clinics. 70 of pet cats stayed indoor and never left house, the
      others (38 cats) lived at house, but frequently abided outdoor. The
      seroprevalence in the last group was higher than in cats kept indoor, in shelters
      or homeless cats, however the differences were not statistically significant.
      Among the cats kept exclusively indoor the statistically significant difference
      in seropositivity was noted between the cats fed raw meat (69.23%) and the ones
      eating only commercial feed or cooked meat (19.35%), chi2 = 17.24, P < 001. Males
      were more frequently infected than females, but the differences were not
      statistically significant. In cats over 5 years old the percentage of positive
      results was significantly higher than in the younger ones. The ranges of antibody
      titres measured by LAT (latex agglutination test) were in agreement with ranges
      estimated by IFAT (indirect fluorescent antibody test). The LAT titres over 1980
      IU/ml and IF IgG titres over 1:4000 were found only in cats, in which clinical
      toxoplasmosis was confirmed.

PMID- 12512556
TI  - The influence of feeding and maintenance system on occurrence of Toxoplasma
      gondii infections in dogs.
AB  - Serum samples of 113 dogs visiting "outpatient clinics", 52 dogs kept in shelters
      and 35 animals from a military dog training centre were examined for Toxoplasma
      gondii specific antibodies using a latex agglutination test. Significant
      differences in seroprevalences were found between dogs from the training centre
      (8.6% of positive results) and the other populations examined (40.7% of positive
      seroreagents in animals visiting outpatient clinics and 44.2% in the group from
      shelters, respectively). Among clinic patients, dogs fed raw meat were
      significantly more frequently seropositive (65.2%) than those eating only
      commercial dry feed or cooked meat (25.7%). No statistically significant
      differences were noted in males compared to females and in pure breed dogs
      compared to crossbreed dogs. The antibodies were usually found in low titres
      under 60 IU/ml (69.6% of positive results). High titres (120-480 IU/ml) were
      detected in 2 of 3 dogs with clinical toxoplasmosis. In these dogs IFAT T. gondii
      specific IgM were detected and a favourable response to antiprotozoal treatment
      was observed. All the dogs with medium and high titres were given raw meat. Age
      and the presence of cats did not seem to have any influence on T. gondii
      seroprevalence. Neospora caninum specific antibodies in low titres ranging from
      1:20-1:320 were found in 7 (9.7%) of 72 T. gondii positive seroreagents.

PMID- 12512557
TI  - Modulation of murine macrophages and T lymphocytes by lysozyme dimer.
AB  - The effects of lysozyme dimer (2 and 20 microg/kg) administered i.p. once and
      four times to mice on the phagocytic and killing ability of peritoneal
      macrophages, interleukin-1 (IL-1) production by murine macrophages stimulated in
      vitro with lipopolisaccharide of E. coli and expression of thymocyte, splenocyte
      and mesenteric lymphonode cell CD3+, CD4+ and CD8+ markers were studied. It was
      found that lysozyme dimer administered once or four times at doses of 2 microg/kg
      and 20 microg/kg augments the phagocytic and killing activity of peritoneal
      macrophages. The strongest stimulating effect was noted after four injections of
      lysozyme dimer at a dose of 20 microg/kg. Moreover, lysozyme dimer is able to
      modulate the production of IL-1 by murine macrophages stimulated in vitro with
      LPS. Exposure to four doses of lysozyme dimer (20 microg/kg) enhances the
      synthesis and release of IL-1, but this drug administered once (2 microg/kg and
      20 microg/kg) or four times (2 microg/kg) decreases IL-1 production by peritoneal
      macrophages. It was also found that administration of lysozyme dimer at a dose of
      20 microg/kg, irrespective of the number of doses applied, increases the
      percentage of CD4+ thymocytes and splenocytes. Moreover, exposure to four doses
      of lysozyme dimer (2 and 20 microg/kg) increases the percentage of CD4+ and CD8+
      mesenteric lymphonode cells.

PMID- 12512558
TI  - Modulatory effects of calf thymus extract on the subset of T lymphocytes in
      Trichinella spiralis-infected mice.
AB  - The immunotropic properties of calf thymus extract (TFX-Jelfa) is connected with
      the mimic action of the thymus to modulate the differentiation, maturation and
      function of prothymocytes and mature thymus dependent (T) cells. The studies were
      carried out on CFW male mice aged 3 months. The animals were infected per os with
      200 larvae of Trichinella spiralis. TFX-Jelfa was administered i.p. at a dose of
      10 mg/kg seven times at 24 hour intervals prior to infection. The percentage of
      CD4+ and CD8+ in suspension of splenocytes and mesenteric lymphonode cells by
      flow cytometry using monoclonal antibodies coupled with fluorescein
      isothiocyanate (FITC) or phycoerythrin (PE) were determined. At the same time,
      cryostat preparations, made from jejunum and muscle samples, were examined by the
      direct immunofluorescence method using FITC-labeled antibody to mouse CD4+ and
      CD8+. It has been found that infection with T. spiralis in mice decreases the
      percentage of CD8+ splenocytes, while the percentage of CD8+ mesenteric
      lymphonode cells does not change. However, in infected mice the percentage of
      CD4+ spleen cells and mesenteric lymphonode cells is increased. It has been also
      found that during the course of infection an increase in the number of CD8+ and
      CD4+ cells in the basal lamina propria of the intestines was observed. In
      infected mice, CD4+ lymphocytes were visible in the inflammatory infiltrates of
      the muscle tissue on the 14th day, whereas CD8+ lymphocytes were first observed a
      week later. Pretreatment with TFX does not change the inhibitory effect of
      infection on the percentage of CD8+ splenocytes, but potentiates the percentage
      of CD4+ spleen cells and mesenteric lymphonode cells increased by infection.
      Furthermore, administration of TFX prior to infection also potentiates the
      stimulatory effect of T. spiralis on the number of CD8+ and CD4+ in the basal
      lamina propria of the jejunum, and on the number of CD8+ cells in the
      inflammatory infiltrates of the muscle tissue.

PMID- 12512559
TI  - Transfer of maternal passive immunity to kids in goat herd.
AB  - The efficiency of tranfer of maternal immunity and its infuence on the kids'
      health was observed in a herd in which kids (n=20) had whole contact with the dam
      (n=13). The factors associated with dam, kid and human, which influence the
      efficiency of passive transfer were observed. It was estimated that the single
      born kids reached higher serum gamma-globulin level (mean 23.14 g/dm3) than twin
      kids (mean 18.2 g/dm3) (p < 0.05). The gamma-globulin level was the highest in
      single-born kids at 48 h, and in twin kids in 24 h of life. The IgG class
      antibodies to herd-homologous strains of Pasteurella multocida and Escherichia
      coli were estimated using ELISA in sera, colostrum and milk whey samples of dams
      and sera of kids. It was found that maternal antibodies specific to these two
      facultative pathogens decreased in kids sera rapidly and the self humoral immune
      response occurred within the period of observation. Two kids delivered by goats
      with lowest hierarchic position in the herd showed failure of passive transfer,
      and died at the 10th and 12th weeks of life due to chronic infections induced by
      both above mentioned bacterial strains.

PMID- 12512560
TI  - Immunohistochemical study of the otic ganglion in the pig.
AB  - The presence of choline acetyltransferase (ChAT), vesicular acetylcholine
      transporter (VAChT), neuropeptide Y (NPY), vasoactive intestinal polypeptide
      (VIP), somatostatin (SOM), galanin (GAL), substance P (SP) and calcitonin gene
      related peptide (CGRP) was studied in neurons and nerve fibers of the porcine
      otic ganglion. ChAT-positive neurons were very numerous while VAChT-positive
      nerve cells were moderate in number. The number of neurons containing NPY and VIP
      was lower and those containing SOM, GAL, SP or CGRP were observed as scarce, or
      single nerve cells. The above mentioned substances (except SOM) were present in
      nerve fibers of the ganglion. ChAT- and VAChT-positive nerve fibers were
      numerous, while the number of nerve terminals containing NPY, VIP and SP was
      lower. GAL- and CGRP-positive nerve fibers were scarce.

PMID- 12512561
TI  - Role of transition metals ion and reactive oxygen species in biological oxidation
      in cattle (part 1).
AB  - Technological advances in last decades of XX centuries were well utilised in the
      studies of biological oxidation processes. Biological oxidation can lead to the
      oxidative stress and subsequently to the cell damage of animal organisms leading
      to many diseases. Free radical processes taking place in cattle under
      pathological conditions. Metal ions are often responsible for the damage of
      biological systems. Fenton and the Fenton like reactions can play the central
      role in the oxidative stress. Transition metal ions and their complexes catalyse
      Fenton and the Fenton like reactions.

PMID- 12512562
TI  - The most important causes for quantitative and qualitative losses during breeding
      and turnover before slaughtering of farm animals.
AB  - The present review article deals with the current knowledge on the most important
      reasons of quantitative and qualitative losses during breeding and turnover
      before slaughtering of farm animals. At present, the profitability of every
      economic activity of people is an indispensable necessity. As regards farm
      animals there are many factors, seemingly banal ones, that determine the final
      economical effect and satisfaction of such activity. Many essential errors are
      made by producers as a result of ignorance or not complying with the basic needs
      of their behaviour. The turnover only deepens these neglects. The most essential
      limitations of these quantitative and qualitative losses are the proper selection
      and joining of the animals as well as an exact knowledge and complying with their
      natural behaviour. Such activity decreases animal stress, improves a proper
      welfare and consequently increases economical effects considerably.

PMID- 12512563
TI  - Ascarid nematodes in domestic and wild terrestrial mammals.
AB  - The biology of the ascarid nematodes has been discussed in the context of their
      important economic role in farm animals, pet animals and zoo animals with special
      attention to carnivores and primates. In farm animals, infection with the most
      common roundworm of horses (Parascaris equorum) and swine (Ascaris suum) depend
      on many factors such as environmental conditions (larval development in the egg
      and egg survival), age of the host, breed, husbandry system, hygiene and
      treatment schedule. The monoxenic ascarids Toxocara canis and T. cati are the
      most important nematodes in carnivorous animals (dogs, cats, foxes) and
      carnivores in the zoo. In the period of March 2000 till March 2001, 57.1% of
      examined representatives of Felidae, Ursidae and Canidae in the Zoological Garden
      of Wroclaw were found to be infected with ascarids (T. canis, T. cati, Toxascaris
      leonina). The prevalence of T. canis in the Canidae was 66.7%, of T. cati in the
      Felidae was 14.3%, while 57.1% of the Felidae carried T. leonina infection.
      Ascaris lumbricoides, a typical parasite of primates, was found in some gorillas,
      chimpanzees and orang-utans during parasitological survey.

PMID- 12512564
TI  - Global situation of foot-and-mouth disease (FMD)--a short review.
AB  - This article reviews the actual world FMD situation. In 2000, fifty nine
      countries officially reported outbreaks of FMD. The disease occurred in Europe
      (Greece), Asia (Russia, Mongolia, Bangladesh, Cambodia, China, Japan, Laos,
      Nepal, Pakistan, Philippines, Republic of Korea, Taiwan, Thailand, Vietnam, Iran,
      Iraq, Turkey, in Caucasian region--Georgia, Azerbaijan and Armenia as well as in
      Kazakhstan, Kyrgyzstan, Turkmenistan and Tajikistan), Africa (Egypt, Kenya,
      Mauritania, South Africa, Tanzania, Uganda, Malawi, Namibia, Zambia and Zimbabwe)
      and in South America (Brazil, Colombia, Uruguay, Bolivia, Peru, Ecuador and
      Venezuela). In 2001, FMD was still spreading throughout the endemic regions and
      appeared in some of the west European countries--Great Britain, The Netherlands,
      France and Ireland. In South America, FMD occurred in Argentina, Uruguay, Brazil
      and Colombia. In Asia the FMD spread in Turkey, Iran, Afghanistan, Georgia,
      Azerbaijan, Mongolia, Kuwait, Bahrain, Yemen, Qatar, United Arab Emirates, Oman,
      Iran, Bhutan, Nepal, Malaysia, Philippines, Thailand and Taiwan. The FMD
      situation in Africa was unclear, but probably most countries in West, East and
      South Africa were affected. The most recent data of the OIE from May 2002
      confirmed FMD outbreaks in population of pigs in Republic of Korea.

PMID- 12512565
TI  - Mapping of quantitative trait loci for body weight at three, six, and nine weeks
      of age in a broiler layer cross.
AB  - An F2 chicken population was established from a cross of a broiler sire-line and
      an egg laying (White Leghorn) line. There were two males and two females from
      both lines in the base population. The F1 progeny consisted of 8 males and 32
      females. Over 500 F2 offspring from five hatches were reared to slaughter at a
      live weight of 2 kg at 9 wk of age. Body weights at 3, 6, and 9 wk were recorded.
      The DNA was extracted from blood samples, and genotypes for 101 microsatellite
      markers were determined. Data of 466 individuals from 30 families were available
      for analysis. Interval mapping QTL analyses were carried out. The QTL significant
      at the genome wide level that affected body weight at two ages were identified on
      chromosomes 1, 2, 4, 7, and 8 and a QTL on Chromosome 13 influenced body weight
      at all three ages. Genetic effects were generally additive, and the broiler
      allele increased body weight in all cases. The effects for significant individual
      QTL accounted for between 0.2 and 1.0 phenotypic standard deviations and the sum
      of the additive effects accounted for approximately 0.75 of the line difference
      in body weight at 6 wk of age. The largest single additive effect was on
      chromosome 4, and the effect of substituting one copy of the gene was an increase
      in weight of 249 g. Interactions of the QTL with sex or family were unimportant.
      There was no evidence for imprinting or of two or more QTL at the same location
      for any of the traits.

PMID- 12512566
TI  - Comparison of three nonlinear and spline regression models for describing chicken
      growth curves.
AB  - This study compared three non-linear growth models (Richards, Gompertz, and
      logistic) and the spline linear regression model using BW measurements from an
      unselected, randombred chicken population. Based on the goodness of fit criteria,
      the nonlinear models (NLM) fitted the data better than the spline regression
      model. The four-parameter Richards model was expected to have the best overall
      fit; however, because the shape parameter predicted was close to 1.0, which
      corresponded with the Gompertz curve, there were no differences between the
      Richards and Gompertz models for the data used. The growth parameters predicted
      with the logistic model were different from those predicted by the Richards and
      Gompertz models. It was concluded that growth parameters predicted with different
      models with fixed inflection points are not directly comparable. The spline
      linear regression model is a compound function consisting of a series of linear
      models. It can be used to compartmentalize growth into segments and also
      substitute as an alternative to asymptotic models when the data are truncated
      before the asymptote is attained. The relationship between the growth trajectory
      (m) and carcass composition measurements were also investigated. Carcass yields
      among the different growth trajectories (m) were similar within sexes. However,
      the proportions of the major breast muscle and abdominal fat differed according
      to the m a bird followed.

PMID- 12512567
TI  - Twelve new turkey microsatellite loci.
AB  - Microsatellite loci continue to be important tools in genetic analysis of
      populations and experimental families. Twelve new microsatellite sequences for
      the turkey were obtained from a small insert M13 library. Polymorphism at these
      new loci was examined in both domestic and wild birds. Seven of 12 loci were
      polymorphic in domestic turkeys, whereas 10 loci were polymorphic in our sample
      of wild birds.

PMID- 12512568
TI  - Effect of physical feed restriction during rearing on Large White turkey breeder
      hens: 3. Body and carcass composition.
AB  - Large White turkey breeder hens were used to evaluate the effect of three
      different levels of physical feed restriction on subsequent body and carcass
      composition. The four feed treatments were 1) ad libitum fed throughout the study
      (CC), 2) feed restricted from 16 to 24 wk (CR), 3) feed restricted from 3 to 16
      wk (RC), and 4) feed restricted from 3 to 24 wk (RR). Feed restriction was
      implemented so that RC and RR hens achieved a 45% reduction in BW compared to CC
      hens at 16 wk. From 16 to 24 wk, feed was allotted to RR and CR hens to maintain
      a slight increase in BW. At the completion of each restriction period, hens were
      gradually returned to ad libitum feeding. At 30 wk, hens were photostimulated for
      a 20-wk summer season egg production cycle. Restricted fed hens had increased
      moisture levels at 16 and 30 wk and decreased fat levels at 16, 30, 39, and 54 wk
      (P < or = 0.05). Absolute and relative weights of the pectoralis major muscle
      were greater in hens fed ad libitum through 43 wk (P < or = 0.05). There were no
      differences in the number of maturing yellow follicles due to treatment. However,
      restricted fed hens had higher peak egg production during early lay but decreased
      subsequent and cumulative egg production. Changes in egg production were
      associated with changes in breast muscle weight. Prolactin levels were greater in
      hens in-production compared to hens out-of-production; however, there were no
      differences due to feed treatment. In conclusion, further research on
      quantitative feed-restriction programs, which result in body weight reductions as
      described in this study, should address specific physiological and nutritional
      requirements and not be implemented as general programs.

PMID- 12512569
TI  - Sequential feeding can increase activity and improve gait score in meat-type
      chickens.
AB  - This study investigated the short- and long-term effects of sequential feeding by
      alternating low-and high-lysine diets during the day on growth, gait score (GS),
      and behavior in broilers. From Days 2 to 12, 6 pens of 10 birds were assigned to
      control treatment and fed a standard normal lysine diet (NL) (ME = 3,250 kcal/kg,
      CP = 23%, Lys = 1.19%) and six pens of 10 birds were assigned to the sequential
      treatment and fed a low-lysine diet (LL) (Lys = 0.85%) for half of the day and NL
      for the other half of the day. From Days 13 to 21, all groups were fed NL, and
      from Days 21 to 42, they were fed a grower diet. Sequential (S) chicks were
      lighter than Control chicks at Days 13 (304 +/- 6 vs. 378 +/- 7 g) and 42 (2,588
      +/- 31 vs. 2,714 +/- 10 g) and had better leg condition at Day 42 (mean GS = 1.6
      +/- 0.1 vs. 2.1 +/- 0.1, P < or = 0.05). During a day of S feeding, S birds ate
      less and wasted more LL than NL. Sequential birds spent less time standing and
      more time lying idle when fed LL than when fed NL. Sequential birds spent more
      time eating than Control birds, and they gradually increased the number of pecks
      in the litter during a sequential feeding day. The results suggest a major effect
      of food composition on behavior. Sequential feeding could be a means of
      decreasing leg problems in broilers.

PMID- 12512570
TI  - Effects of the tricothecene mycotoxin diacetoxyscirpenol on egg production of
      broiler breeders.
AB  - Three experiments were conducted to determine the effects of 4,15
      diacetoxyscirpenol (DAS) on egg quality and egg production of broiler breeders.
      In Experiment 1, feed containing 0, 1.25, 2.5, or 5.0 mg DAS/ kg was fed from 67
      to 69 wk of age followed by a 3-wk recovery period on a slat-litter floor. In
      Experiment 2, individually caged broiler breeder females were studied from 23 to
      31 wk of age. The basal diet containing 0, 5, 10, or 20 mg DAS/kg was fed from 25
      to 27 wk of age. In Experiment 3, individually caged broiler breeder hens were
      studied from 23 to 32 wk of age. DAS was fed at levels of 0 (basal), 5, 10, and
      20 mg DAS/kg for 2 wk beginning at Week 24, followed by the basal breeder diet
      for 7 wk. Egg production was not affected by levels of up to 5 mg DAS/kg in the
      older hens of Experiment 1. When fed from 25 to 27 wk of age in Experiment 2, DAS
      decreased egg production at the 20 mg/kg level only. When fed from 24 to 25 wk of
      age in Experiment 3, DAS had no significant effect on egg production or egg
      quality. Short-term consumption of DAS at levels that might naturally occur
      appears to have little effect on broiler breeder egg production.

PMID- 12512571
TI  - The localization and uptake of in ovo injected soluble and particulate substances
      in the chicken.
AB  - The localization of in ovo injected substances in the chicken was investigated.
      We determined that localization is dependent on the nature of substances and the
      time of in ovo injection. In ovo injections with soluble bromodeoxyuridin (BrdU),
      particulate colloidal carbon, 40 nm fluorescent microspheres, and live Infectious
      Bursal Disease Virus (IBDV) were performed with a 25-mm (1-in) needle at Days 16
      and 18 of incubation (DI-16 and DI-18, respectively). Localization of injected
      substances was determined in several organs using immunocytochemical methods. At
      DI-16, approximately 50% of the substances were detected in the organs;
      therefore, the localization of substances was not consistent. At DI-18, the
      substances were injected into the amnion. The substances entered the embryo by
      the mouth and were ingested into the intestinal and respiratory tract. All
      substances reached the lungs of the embryo via the trachea and the bronchi and
      were absorbed by the gas exchange tissue. In addition, the substances were
      absorbed by the bursa. Particulate colloidal carbon and microspheres remained in
      the organs where they were taken up initially for the rest of time of the
      experiment. Live IBDV, however, was distributed to other organs of the embryo.
      Soluble BrdU was found in all investigated organs of the embryo in high amounts.
      These results demonstrate that in ovo injection at DI-18 is an effective route to
      introduce substances into the chicken embryo, whereby the characteristics of the
      substance determine its final localization.

PMID- 12512572
TI  - Hatchery and transportation factors associated with early poult mortality in
      commercial turkey flocks.
AB  - A prospective ecologic study, using routinely collected data from commercial
      turkey companies, was done of 312 turkey flocks placed over a 1-yr period. The
      objective was to identify hatchery- and transportation-associated risk factors
      for poult mortality in the first 14 d after placement using statistical models.
      Logistic regression was used to determine the effects of hatchery-and
      transportation-related factors on odds of mortality for hen and tom flocks
      separately. Hatchery and transportation-related risk factors for hen flock
      mortality included truck, truck temperature, and number of poults dead on arrival
      at the farm. Hatchery and transportation-related risk factors for tom flock
      mortality included desnooding, truck, truck temperature, shipping time, and
      weather conditions at placement.

PMID- 12512573
TI  - Biochemical and immunological changes in chickens experiencing pulmonary
      hypertension syndrome caused by Enterococcus faecalis.
AB  - Recent studies have proven that Enterococcus faecalis (1.5 x 10(7) live bacteria
      from a tryptic broth culture given s.c. or intra-abdominally (IA) to 5-wk-old
      broilers) caused pulmonary hypertension syndrome (PHS) in 97% of the birds within
      48 h. Definitive diagnosis of PHS was made at necropsy by observing a cavity on
      the surface of the right ventricular wall and by increased ratio of left
      ventricular weight to total ventricular weight. A nonlethal method of diagnosing
      PHS would enhance the study of PHS and alert production poultrymen to the onset
      of ascites (waterbelly), which is the cuLminating event of PHS. In the present
      study, serum hemoglobin, glucose, protein, cholesterol, aspartate amino
      transferase (AST) and creatine kinase-MB (myocardial in origin) enzymes,
      differential leukocyte numbers, and specific antibody levels against Ent.
      faecalis were evaluated as nonlethal diagnostic indicators of PHS. Decreases in
      serum protein and cholesterol of 3 and 10%, respectively, plus increases in
      percentages of basophils and monocytes of 18 and 40%, respectively, appear to
      indicate that PHS has been initiated. An agglutinating antibody, specific against
      Ent. faecalis, but not against other closely related bacteria, has been
      developed. Presence of this antibody in a bird means that the bird has previously
      encountered Ent. faecalis. Thus, this antibody may become a diagnostic for PHS in
      fast-growing chickens.

PMID- 12512574
TI  - Single-strand conformation polymorphism (SSCP) assays for major
      histocompatibility complex B genotyping in chickens.
AB  - We have developed a DNA-based method for defining MHC B system genotypes in
      chickens. Genotyping by this method requires neither prior determination of
      allele-specific differences in nucleotide sequence nor the preparation of
      haplotype-specific alloantisera. Allelic differences at chicken B-F (class I) and
      B-L (class II) loci are detected in PCR single-strand conformation polymorphism
      (SSCP) assays. PCR primer pairs were designed to hybridize specifically with
      conserved sequences surrounding hypervariable regions within the two class I and
      two class I loci of the B-complex and used to generate DNA fragments that are
      heat- and formamide-denatured and then analyzed on nondenaturing polyacrylamide
      gels. PCR primer pairs were tested for the capacity to produce SSCP patterns
      allowing the seven B haplotypes in the MHC B congenic lines, and seven B
      haplotypes known to be segregating in two commercial broiler breeder lines to be
      distinguished. Primer pairs were further evaluated for their capacity to reveal
      the segregation of B haplotypes in a fully pedigreed family and in a closed
      population. Concordance was found between SSCP patterns and previously assigned
      MHC types. B-F and B-L SSCP patterns segregated in linkage as expected for these
      closely linked loci. We conclude that this method is valuable for defining MHC B
      haplotypes and for detecting potential recombinant haplotypes especially when
      used in combination with B-G (class IV) typing by restriction fragment pattern.

PMID- 12512575
TI  - Addition of enzyme to starter and grower diets for ducks.
AB  - The growth performance and nutrient utilization responses of White Pekin ducks to
      a commercial enzyme preparation were investigated. The enzyme contained 4,000
      units amylase, 12,000 units protease, and 1,600 units xylanase per gram. Twelve
      pens of 10 ducks were fed diets based on corn and soybean meal and wheat
      middlings. The diets contained the enzyme mixture at 0, 0.375, or 0.5 g/kg in a
      growth study for 42 d. At the end of growth study, four ducks from each of eight
      pens per diet were retained and continued their respective diets containing 2.5 g
      Cr2O3/kg for 7 d. Intestinal content was sampled to determine ileal
      digestibilities of energy, nitrogen, and amino acids. One duck from each pen was
      selected at the end of the growth study and was fitted with retainer rings around
      the vent for the attachment of an excreta collection apparatus; these ducks were
      maintained on their respective diets containing 2.5 g Cr2O3/ kg to determine
      dietary nitrogen, amino acids, and energy retention. Results from the performance
      study showed a 6 to 8% increase (P < 0.05) in BW gain for birds fed diets
      containing the enzyme. There was also an enzyme-related improvement in feed
      efficiency (P < 0.05) over the 42-d study. Ileal nitrogen digestibility was
      highest (P < 0.05) for ducks fed diets containing the enzyme preparation at 0.5
      g/kg, but ileal digestibility of energy was not affected by enzyme
      supplementation of diets. Apparent nitrogen retention was greater (P < 0.05) in
      ducks that received enzyme at 0.5 g/kg diet than in ducks fed diets without the
      enzyme. Energy retention (AME and AMEn) of diets was not affected by the addition
      of enzyme to diets. Excreta amino acid digestibilities were found to be
      consistently higher than ileal estimates. The mean ileal amino acid digestibility
      coefficients in diets with enzyme at 0, 0.375, and 0.5 g/kg were 86.94, 88.82,
      and 88.87%, respectively. The addition of enzyme improved (P < 0.05) ileal amino
      acid digestibility and apparent amino acid retention. The study indicates that
      dietary enzyme supplementation improved growth performance, nitrogen, and amino
      acid retention of White Pekin ducks.

PMID- 12512576
TI  - Influence of whole barley and grit on live performance and health of turkey toms.
AB  - Live performance to 96 d was compared for 1,584 turkey toms reared on diets
      containing four levels of whole barley and two levels of insoluble grit (0 or 9
      g/bird per wk). Nutrient specifications for all diets were similar. The six
      dietary treatments were 1) 0% whole barley plus grit, 2) Treatment 1 minus grit,
      3) grit plus 5% whole barley at 0 d increasing to 35% by 19 d, 4) grit plus 5%
      whole barley at 0 d increasing to 50% by 19 d, 5) Treatment 4 minus grit, and 6)
      grit plus 5% whole barley at 19 d increasing to 50% by 40 d. The concentrate
      blended with the whole barley was fed as crumbles or pellets. Nutrients were not
      diluted. Compared to the control treatments, feeding 35% or more whole barley
      temporarily reduced weight gain and increased feed:gain prior to 68 d. Cumulative
      weight gain was reduced in Treatments 3 and 5 compared to treatments in which no
      barley was fed. Cumulative feed:gain was increased in Treatment 5 compared to
      Treatments 2 and 3. Total mortality and leg and skeletal problems were reduced in
      treatments where whole grain slowed early growth rate. Feeding grit had no effect
      on the live performance of birds fed similar levels of whole barley. In
      treatments in which whole barley was introduced at 0 d, gizzard pH was decreased
      at 18 d, and gizzard weight was increased at 32 d. Jejunal viscosity was
      unaffected by dietary treatment.

PMID- 12512577
TI  - Effects of dietary garlic on cholesterol metabolism in laying hens.
AB  - Experiments were conducted to evaluate the potential for dietary garlic to
      influence egg yolk cholesterol concentrations and overall performance in
      different layer strains. Thirty-six, 28-wk-old, Hisex Brown,Isa Brown, Lohmann,
      Starcross, Babcock, and Starcross-579 strains (six hens per strain) were fed
      diets supplemented with 0 (control), 2, 4, 6, 8, or 10% sun-dried garlic paste
      for 6 wk. There were no differences (P > 0.05) among diets or strains in egg
      weight, egg mass, feed consumption, feed efficiency, and BW gain as averaged over
      6 wk. Yolk weight, however, responded quadratically with increasing levels of
      dietary garlic and differed among strains (P < 0.05). Egg production and yolk
      weights were significantly higher in the Babcock strain in comparison with other
      strains. Serum and egg yolk cholesterol concentrations decreased linearly (P <
      0.05) with increasing levels of dietary garlic. Serum and egg yolk cholesterol
      concentrations also differed among different strains (P < 0.05). It was concluded
      that garlic paste in the diets of laying hens reduced serum and yolk cholesterol
      concentrations. It was also concluded that dietary garlic paste had no adverse
      effects on layer performance.

PMID- 12512578
TI  - Lysine need of heavy broiler males applying the ideal protein concept.
AB  - An experiment was conducted to measure the response of broiler males to dietary
      lysine progressing from 0.75 to 1.15% between 42 and 56 d of age. Chicks (Ross x
      Ross 308) were placed in floor pens (30 pens having 35 chicks each) of an open
      sided house and provided common feeds to 42 d of age. From 42 to 56 d, a corn
      soybean meal diet (18% CP and 3,250 kcal/kg ME) having total lysine at 0.75% was
      supplemented with additions of 0.10% until 1.15%. All other essential amino adds
      were "ideally" balanced to one another within the limits of practicality assuming
      0.85% total lysine. Birds had continuous access to feed, water, and light. Live
      performance during experimentation was particularly favorable. Weight gain
      between 42 and 56 d of age was similar among birds receiving all levels of
      lysine, while feed conversion was optimized at 0.85%. Depot fat removed from the
      abdominal cavity, yield of the resultant chilled carcass, and the amount of
      fillet (pectoralis major) cone deboned from the breast were unaltered by dietary
      lysine level. However, yield of tenders (pectoralis minor) decreased as
      supplemental lysine increased, whereas the incidence of myopathy (green muscle
      disease) increased. The lysine requirement of 0.85% as advocated by NRC (1994)
      for broilers between 42 and 56 d of age is in agreement with present results and
      may have been predisposed by its favorability of balance with all other essential
      amino adds.

PMID- 12512579
TI  - Re-evaluation of the isoleucine requirement of the commercial layer.
AB  - An experiment was conducted with Hy-Line W36 hens to re-evaluate their Ile
      requirements from a corn-soybean meal diet. Eight experimental diets were fed
      with Ile levels of 0.60, 0.57, 0.54, 0.51, 0.48, 0.45, 0.42, and 0.39%.
      Supplemental amino acids (AA) were added to ensure that ILe was the first
      limiting AA. Increasing levels of Ile above 0.51% significantly increased egg
      production (EP), egg weight (EW), and egg mass (EM). Egg production, EW, and EM
      decreased each time the Ile content of the diet was decreased. Feed consumption
      (FC) and energy intake were not significantly decreased until the diet contained
      0.45% Ile, and, at this time, BW was significantly reduced. Broken-line
      regression indicated a daily Ile requirement of 449.8, 497.0, and 469.0 mg/d for
      EP, EW, and EM, respectively, which indicated a requirement of 9.30 mg Ile/g EM.

PMID- 12512580
TI  - Accumulation of alpha-tocopherol in eggs enriched with omega3 and omega6
      polyunsaturated fatty acids.
AB  - The objective of the present study was to evaluate the pattern of accumulation of
      alpha-tocopherol (alpha-Toc) in egg as a response to dietary supplementation with
      200 mg/kg diet of alpha-tocopheryl acetate (alpha-TA) and whether the inclusion
      of dietary oils with different fatty acid (FA) composition affected this
      parameter. Forty hens were randomly distributed into two treatments resulting
      from the supplementation of a basal diet containing 200 mg/kg alpha-TA with
      either 5% linseed oil (LO) or sunflower oil (SO). alpha-Tocopherol concentration
      of eggs was measured at 0, 4, 9, 14, 19, and 50 d after inclusion of the
      experimental diets. Results show that alpha-Toc concentration in the egg
      increased after the 4th d of feeding, reaching its maximum level at 14 d (168
      microg/g egg), after which it decreased 10 to 12% until 19 d, obtaining similar
      values at 50 d (145 microg/g egg). No differences were observed between dietary
      oils in the deposition pattern of alpha-Toc in the egg.

PMID- 12512581
TI  - Isolation and unique composition of purified head plasma membrane from rooster
      sperm.
AB  - The structure, composition, and function of membranes from organelles of
      mammalian spermatozoa differ from each other and from the sperm's plasma
      membrane. Avian sperm studies have suffered from the lack of a technique to
      isolate these various membranes, which the current study now provides. Nitrogen
      cavitation and differential centrifugation separated head plasma membranes (HPM)
      of rooster sperm from sperm debris, acrosomal membranes, and mitochondrial
      membranes and characterized these membranes enzymatically and microscopically.
      The HPM was enriched in acid phosphatase (marker enzyme for HPM; 1,814.81 +/-
      470.43 micromol phosphate released/microg protein vs. 868.53 +/- 75.55 for whole
      semen; a 202.5 +/- 37.8% enrichment, mean +/- SE, P < 0.001), with less (P <
      0.001) mitochondrial and acrosomal enzyme activity. The mitochondrial fraction
      had 515.1 +/- 167.6% more succinate dehydrogenase activity (marker for
      mitochondria, P < 0.001) and the acrosomal fraction had 315.4 +/- 61.2% more
      acetylglucosaminidase activity (marker for acrosome, P < 0.0001) than whole
      semen. Thin layer and gas chromatography showed that HPM lipids had more (P <
      0.05) sphingomyelin and phosphatidylserine, and less phosphatidylcholine and
      phosphatidylethanolamine than did the sperm body membranes (SBM). Overall, HPM
      had less polyunsaturated fatty acids than SBM (36.8 +/- 3.4 vs. 44.5 +/- 1.7% of
      total phospholipids, P < 0.05). HPM had slightly more n3 (3.2 +/- 0.5 vs. 1.3 +/-
      0.2%, P < 0.01) but much less n6 (33.6 +/- 3.3 vs. 43.3 +/- 1.9%, P < 0.01),
      specifically less C22:4n6. Future study of avian sperm will be able to reliably
      characterize the structure-function relationships of specific sperm membranes.

PMID- 12512582
TI  - Effects of F-strain Mycoplasma gallisepticum inoculation at twelve weeks of age
      on digestive and reproductive organ characteristics of commercial egg laying
      hens.
AB  - Experimental inoculation with the F-strain of Mycoplasma gallisepticum (FMG)
      between 8 and 18 wk of age is known to affect reproductive performance in
      commercial layers. Therefore, two trials were conducted to determine if changes
      in digestive and reproductive organ characteristics also occur in commercial
      laying hens infected with FMG at 12 wk of age. In Trial 1, liver weight, liver
      lipid and moisture contents, ovary weight, ovarian follicular hierarchy, and the
      weights, lengths, and histologies of the infundibulum, magnum, isthmus, uterus,
      and vagina were determined. In Trial 2, fatty liver hemorrhagic syndrome (FLHS)
      incidence and the weights, lengths, and histologies of the duodenum, jejunum, and
      ileum were determined in addition to the parameters examined in Trial 1. In both
      trials, the average number of mature (diameter > or = 12 mm) ovarian follicles
      was lower in FMG-inoculated hens in comparison to controls. Also, magnum/oviduct
      (cm/cm) length was reduced in treated birds. In Trial 2, isthmus/BW and
      isthmus/oviduct (g/ g) weight were decreased at 46 wk of age, and vagina/ BW and
      vagina/oviduct (g/g) weight were decreased at both 20 and 36 wk of age due to FMG
      treatment. In Trial 2, FMG treatment resulted in a 50% increase in the number of
      FLHS birds. Furthermore, treatment caused a decrease at 20 wk of age and an
      increase at 44 wk of age in liver moisture content. However, the intestinal
      characteristics examined were not affected by FMG inoculation. Altered liver,
      ovarian, and reproductive organ characteristics were associated with FMG
      infection in commercial layers. More specifically, FMG inoculation at 12 wk
      resulted in a higher incidence of FLHS, ovarian follicular regression, and
      decreased isthmal and vaginal proportions of the reproductive tract. These data
      clearly demonstrate that alterations in performance and egg characteristics of
      layers inoculated with FMG at 12 wk of age are related to mutual functional
      disturbances in the liver, ovary, and oviduct without concomitant intestinal
      changes.

PMID- 12512583
TI  - Elevated body temperature directly contributes to heat stress infertility of
      broiler breeder males.
AB  - Alterations in the male reproductive tract, sperm, or both may be responsible for
      heat stress infertility of broiler breeder males. The present study was conducted
      to determine the direct effects of hyperthermia during heat stress on sperm
      viability, the spermquality index (SQI), and seminal plasma ion concentrations by
      incubation of semen in vitro at and above normal body temperature. Thirty-seven
      Cobb males were divided into the upper (best group = B) and lower (poor group =
      P) 50% of the population according to their SQI. Semen characteristics and
      seminal plasma ion concentrations (Ca++, Na+, K+, and Cl-) for B and P males were
      evaluated at two temperature treatments (41.5 and 42.5 C) and four incubation
      times (0, 30, 60, and 90 min). The results revealed that sperm viability and the
      SQI were decreased by increasing incubation temperature and duration of exposure.
      Seminal plasma ion concentrations were not affected by semen incubation
      temperature; however, plasma Ca++ concentration in the P-SQI group was higher
      than that of the B-SQI group. Seminal plasma K+ concentration increased in both
      SQI groups over time. In conclusion, it is apparent that changes in semen
      characteristics due to elevated body temperature alone contribute to heat stress
      infertility of broiler breeders.

PMID- 12512584
TI  - Effect of melatonin supplementation on the ontogeny of immunity in the Large
      White turkey poult.
AB  - An experiment was performed to determine the effect of melatonin supplementation
      on the ontogeny of immunity in the Large White turkey poult. Melatonin (50
      microg/mL) or diluent only (control) was administered via the drinking water from
      hatch to 28 d of age. The cutaneous basophil hypersensitivity (CBH) reaction to
      phytohemagglutinin (PHA-P) and primary antibody responses to Chukar red blood
      cells (CRBC) were determined at five intervals; 0, 1, 7, 14, and 21 d posthatch.
      At each of these times, including 28 d posthatch, 10 poults were killed and
      lymphoid organ and body weights were determined. Melatonin administration
      accelerated (P < or = 0.05) the development of cell-mediated (PHA-P-induced CBH
      reaction) and humoral (CRBC-induced antibody titer) immune responses, and these
      responses were elevated above controls through 21 d posthatch. The bursal weight,
      but not thymus or spleen, was elevated in melatonin treated poults as compared to
      controls. Body weights were increased in melatonin treated poults as compared to
      controls. These data suggest that posthatch melatonin supplementation is
      beneficial to neonatal immune parameters and growth responses of Large White
      turkey poults.

PMID- 12512585
TI  - Role of seminal plasma in heat stress infertility of broiler breeder males.
AB  - The present research was undertaken to determine the role of seminal plasma in
      heat stress (HS) infertility. Males were exposed to HS at 32 C or maintained at
      21 C as controls. Centrifugation and reconstitution of semen samples created four
      final treatments: control sperm + control plasma (CsCp), control sperm + HS
      plasma (CsHp), HS sperm + HS plasma (HsHp), and HS sperm + control plasma (HsCp).
      Semen samples with HS males' seminal plasma had lower sperm quality index values
      than those containing plasma from control males. Seminal plasma from HS males
      diminished fertility of control sperm, and control seminal plasma did not improve
      fertility of HS sperm. Therefore, regardless of seminal plasma source, HS sperm
      had a lower fertilization rate than control sperm. Also, seminal plasma from
      semen samples with HS sperm (HsHp and HsCp) contained lower Ca, Na+ and Cl-
      concentrations than seminal plasma from semen samples with control sperm (CSCp
      and CsHp). When HS seminal plasma was mixed with control sperm, plasma ion
      concentrations increased, indicating an efflux of ions from the control sperm to
      the HS seminal plasma. On the other hand, when control seminal plasma was mixed
      with HS sperm, plasma ion concentrations decreased, indicating an influx of ions
      from the control seminal plasma to the HS sperm. Therefore, control sperm appear
      to have higher intracellular ion concentrations than the sperm from HS males. In
      conclusion, high temperatures might decrease male fertility by decreasing seminal
      plasma and intracellular ion concentrations.

PMID- 12512586
TI  - Texture and microstructure properties of frozen chicken breasts pretreated with
      salt and phosphate solutions.
AB  - This study investigated the effects of 10% NaCl, trisodium phosphate (TSP),
      sodium tripolyphosphate (STPP), and tetrapotassium pyrophosphate (TKPP)
      treatments on textural and microstructural properties of chicken breasts during
      10 mo of frozen storage at -20 C. Fresh chicken breasts were treated for 10 min
      with 10% NaCl and various phosphate solutions, including TSP, STPP, and TKPP, and
      stored in a -20 C freezer for 10 mo. Frozen chicken breasts were completely
      thawed at 4 C and oven-baked at 177 C for 20 min. Shear force, drip loss, and
      cooking loss were measured. In addition, ice crystal formation and structure
      changes of frozen chicken breasts during storage were evaluated using
      transmission electron microscopy (TEM). Treating chicken breasts with 10% TSP and
      STPP solution significantly reduced drip and cooking losses as well as minimized
      ice crystal formation and freeze-induced shrinkage of myofibrils. No significant
      texture toughening was observed in frozen chicken breasts regardless of
      treatments. These results suggest that the perceived quality losses of frozen
      chicken breast were not associated with texture toughening. The water-binding
      ability of chicken meat was the most important factor in maintaining the quality
      of chicken breast during extended frozen storage, which can be accomplished by
      treating chicken breasts with 10% TSP and STPP solutions before frozen storage.

PMID- 12512587
TI  - Color of uncooked and cooked broiler leg quarters associated with chilling
      temperature and holding time.
AB  - Discoloration of raw or cooked tissue can occur from cell disruptions and blood
      migration caused by slow or variable chilling rates. Color parameters established
      by the Commission International D'Eclairage for measuring lightness, redness, and
      yellowness (L*, a*, and b* respectively) were determined on two groups (A and B)
      of uncooked and cooked leg quarters chilled at +4, 0, -3, -12, or -18 C. At Day
      7, group A was evaluated for color, and group B was moved to -18 C for seven
      additional days and then evaluated. Group B represented cooling, freezing,
      thawing, and cooking steps. Color was measured on surfaces of thawed, uncooked
      parts (UCS), on surfaces of cooked parts (CS) 75 or 85 C internal temperature),
      and on cooked meat (CM) adjacent to the femur. UCS samples at -3 C were
      significantly redder (a* = 8.91) than -18 C samples (a* = 5.04). The A-CS a*
      values showed a significant interaction between chill temperature storage and
      internal temperature (IT). Samples at 75 C IT had higher a* values (redder). CM
      samples held at +4 and 0 C were significantly lighter (higher L* values). A
      significant interaction effect occurred for CM a* values due to storage chill
      temperature and IT. Generally, 75 C IT samples were redder (higher a* values).
      UCS and CS color was not influenced by chilling at +4 to -18 C for 7 d and then
      at -18 C for 7 d. CM was affected by a combination of chill temperature history
      and IT.

PMID- 12512588
TI  - Micellar casein gelation at high sucrose content.
AB  - This article investigates the effect of sucrose addition on the formation of
      casein gels by acidification and/or renneting of pure micellar casein. Gelation
      kinetics and gel properties were followed by rheological methods, and microscopy
      and syneresis measurements were used to obtain a more complete characterization
      of the structures formed. Sucrose content has been identified as a key parameter
      for controlling the kinetics of aggregation and the strength of the final gels.
      Results have shown that the effect of sucrose on gelation can vary such that
      effects can be completely reversed depending on the gelation route used. During
      acid gelation, addition of up to 30% (wt/wt) sucrose causes gels to form more
      rapidly and at higher pH values, and to have higher viscoelastic moduli and a
      more homogeneous microstructure than those without sucrose. By contrast, gels
      formed by renneting in the presence of sucrose are weaker and have longer
      gelation times. It is proposed that sucrose reduces solvent quality and causes
      the collapse of the "hairy" kappa-casein brush on the surface of the casein
      micelles. This may explain why sucrose increases the possibility of gel formation
      during acidification and reduces the degree of kappa-casein hydrolysis during
      renneting.

PMID- 12512589
TI  - Effect of wild strains of Lactococcus lactis on the volatile profile and the
      sensory characteristics of ewes' raw milk cheese.
AB  - The production of volatile compounds by wild strains of Lactococcus lactis used
      as starter cultures and their effect on the sensory characteristics of ewes' raw
      milk cheese were investigated. Sixteen vats of cheese were manufactured and
      ripened for 120 d in two experiments, each of them duplicated. In the first
      experiment, milk was inoculated with different ratios of four wild Lactococcus
      lactis strains, two producing and two not producing branched-chain volatile
      compounds, and in the second experiment with different ratios of a commercial
      starter culture and the two strains producing branched-chain volatile compounds.
      Cheese pH, proteolysis, and aminopeptidase activity increased when the strains
      producing branched-chain volatile compounds were inoculated at a higher rate.
      Fifty volatile compounds were identified in cheeses using a purge and trap system
      coupled to a gas chromatography-mass spectrometry apparatus. The relative
      abundances of 30 volatile compounds (8 alcohols, 5 aldehydes, 3 ketones, 12
      esters, 1 sulfur compound, and 1 benzenic compound) were influenced by starter
      culture composition. 2-Methylpropanol, 3-methylbutanol, isobutyl acetate, isoamyl
      acetate, ethyl butyrate, isobutyl butyrate, and isoamyl butyrate were always more
      abundant in the cheeses made with a higher level of L. lactis strains producing
      branched-chain volatile compounds. Flavor intensity was enhanced by a high level
      of L. lactis strains producing branched-chain volatile compounds in the first
      experiment, in which four wild L. lactis strains were used as starter culture,
      but not in the second experiment, in which a combination of two wild L. lactis
      strains and the commercial starter culture were used. Flavor quality, as judged
      by trained panelists, was impaired in both experiments by a high level of L.
      lactis strains producing branched-chain volatile compounds.

PMID- 12512590
TI  - Estimation and fortification of vitamin D3 in pasteurized process cheese.
AB  - The objective of this study was to develop methods for the estimation and
      fortification of vitamin D3 in pasteurized Process cheese. Vitamin D3 was
      estimated using alkaline saponification at 70 degrees C for 30 min, followed by
      extraction with petroleum ether:diethyl ether (90:10 vol/vol) and HPLC. The
      retention time for vitamin D3 was approximately 9 min. A standard curve with a
      correlation coefficient of 0.972 was prepared for quantification of vitamin D3 in
      unknown samples. In the second phase of the study, pasteurized Process cheeses
      fortified with commercial water- or fat-dispersible forms of vitamin D3 at a
      level of 100 IU per serving (28 g) were manufactured. There was no loss of
      vitamin D3 during Process cheese manufacture, and the vitamin was uniformly
      distributed. No losses of the vitamin occurred during storage of the fortified
      cheeses over a 9-mo period at 21 to 29 degrees C and 4 to 6 degrees C. There was
      an approximately 25 to 30% loss of the vitamin when cheeses were heated for 5 min
      in an oven maintained at 232 degrees C. Added vitamin D3 did not impart any off
      flavors to the Process cheeses as determined by sensory analysis. There were no
      differences between the water- and fat-dispersible forms of the vitamin in the
      parameters measured in fortified cheeses.

PMID- 12512591
TI  - Cholesterol removal from media by lactococci.
AB  - Elevated serum cholesterol in humans is generally a risk factor correlated with
      the development of coronary heart disease. It has been reported that a culture of
      Lactobacillus acidophilus actively taking up cholesterol from a laboratory medium
      would function in vivo to exert a hypocholesterolemic effect. In the present
      study, seven strains of the genus Lactococcus were examined for their ability to
      remove cholesterol from laboratory media during growth. All strains of lactococci
      tested could remove cholesterol from media without degrading cholesterol. The
      amount of cholesterol removed was strain specific. Among them, Lc. Lactis subsp.
      lactis biovar diacetylactis N7 could remove as much cholesterol as L. acidophilus
      ATCC 43121, which had a beneficial influence on serum cholesterol levels in pigs.
      The manner of cholesterol removal by strain N7 corresponded to the manner of its
      growth. The growth of strain N7 (growth yield and growth efficiency) was
      enhanced. The fatty acid composition of the cells of strain N7 was altered by
      removing cholesterol from the media. The ability to remove cholesterol was also
      observed in the heat-killed cells of strain N7. However, the amount of
      cholesterol removed by the cells during growth was significantly higher than that
      removed by the heat-killed cells. Thus, strain N7 has the ability to remove
      cholesterol from media independently of whether cells are viable. These results
      indicate that administration of strain N7 in vivo may well be promising on the
      hypocholesterolemic effect.

PMID- 12512592
TI  - Production of an exopolysaccharide-containing whey protein concentrate by
      fermentation of whey.
AB  - Using whey as a fermentation medium presents the opportunity to create value
      added products. Conditions were developed to partially hydrolyze whey proteins
      and then ferment partially hydrolyzed whey with Lactobacillus delbrueckii ssp.
      bulgaricus RR (RR; an EPS-producing bacterium). In preliminary experiments,
      pasteurized Cheddar cheese whey was treated with Flavourzyme to partially
      hydrolyze the protein (2 to 13% hydrolyzed). Fermentation (2 L, 38 degrees C, pH
      5.0) with RR resulted in EPS levels ranging from 95 to 110 mg of EPS per liter of
      hydrolyzed whey. There were no significant differences in the amount of EPS
      produced during fermentations of whey hydrolyzed to varying degrees. Since a high
      level of hydrolysis was not necessary for increased EPS production, a low level
      of hydrolysis (2 to 4%) was selected for future work. In scale up experiments,
      whey was separated and pasteurized, then treated with Flavourzyme to hydrolyze 2
      to 4% of the protein. Following protease inactivation, 60 L of partially
      hydrolyzed whey was fermented at 38 degrees C and pH 5.0. After fermentation, the
      broth was pasteurized, and bacterial cells were removed using a Sharples
      continuous centrifuge. The whey was then ultrafiltered and diafiltered to remove
      lactose and salts, freeze-dried, and milled to a powder. Unfermented hydrolyzed
      and unhydrolyzed whey controls were processed in the same manner. The EPS-WPC
      ingredients contained approximately 72% protein and 6% EPS, but they exhibited
      low protein solubility (65%, pH 7.0; 58%, pH 3.0).

PMID- 12512593
TI  - Effect of pasteurization on survival of Mycobacterium paratuberculosis in milk.
AB  - Mycobacterium paratuberculosis (Mptb) is the causative agent of Johne's disease
      of ruminant animals including cattle, goats, and sheep. It has been suggested
      that this organism is associated with Crohn's disease in humans, and milk is a
      potential source of human exposure to this organism. A total of 18, including 7
      regular batch and 11 high temperature short time (HTST) pasteurization
      experiments, were conducted in this study. Raw milk or ultra-high temperature
      pasteurized milk samples were spiked at levels of 10(3), 10(5), and 10(7) cfu of
      Mptb/ml. Escherichia coli and Mycobacterium bovis BCG strains at 10(7) cfu/ml
      were used as controls. Pasteurization experiments were conducted using time and
      temperature standards specified in the Canadian National Dairy Code: regular
      batch pasteurization method: 63 degrees C for 30 min, and HTST method: 72 degrees
      C for 15 s. The death curve of this organism was assessed at 63 degrees C. No
      survivors were detected after 15 min. Each spiked sample was cultured in
      Middlebrook 7H9 culture broth and Middlebrook 7H11 agar slants. Samples selected
      from 15 experiments were also subjected to BACTEC culture procedure. Survival of
      Mptb was confirmed by IS900-based PCR of colonies recovered on slants. No
      survivors were detected from any of the slants or broths corresponding to the
      seven regular batch pasteurization trials. Mptb survivors were detected in two of
      the 11 HTST experiments. One was by both slant and broth culture for the sample
      spiked to 10(7) cfu/ml of Mptb, while the other was detected by BACTEC for the
      sample spiked to 10(5) cfu/ml. These results indicate that Mptb may survive HTST
      pasteurization when present at > or = 10(5) cfu/ml in milk. A total of 710 retail
      milk samples collected from retail store and dairy plants in southwest Ontario
      were tested by nested IS900 PCR for the presence of Mptb. Fifteen percent of
      these samples (n = 110) were positive. However, no survivors were isolated from
      the broth and agar cultures of 44 PCR positive and 200 PCR negative retail milk
      samples. The lack of recovery of live Mptb from the retail milk samples tested
      may be due to either the absence of live Mptb in the retail milk samples tested
      or the presence of low number of viable Mptb which were undetected by the culture
      method used in this study.

PMID- 12512594
TI  - Stress responses during milking; comparing conventional and automatic milking in
      primiparous dairy cows.
AB  - A comparative study was performed to evaluate the differences in behavioral and
      physiological stress responses during milking between cows that were milked by an
      automated milking system (AM-cows) and cows that were milked in a conventional
      tandem parlor (TM-cows). In a randomized design, 36 primiparous Holstein-Friesian
      dairy cows were observed and blood sampled (1-min intervals) individually during
      milking. AM-cows spent less time standing with their heads outside the feeding
      trough than TM-cows and had a lower heart rate. In addition, AM-cows had lower
      maximum plasma adrenaline and noradrenaline concentrations during milking. No
      differences were found in the number of steps. After tactile stimulation of the
      teats either by hand or by the cleaning brush, mean oxytocin concentrations did
      not differ. In AM-cows, however, elevated oxytocin levels were prolonged at the
      end of milking. Averaged over the first five blood samples, AM-cows tended to
      have higher plasma cortisol concentrations than TM-cows, but median fecal
      concentrations of the cortisol metabolite dioxoandrostane were comparable.
      Maximum quarter milk flow, maximum udder milk flow and residual milk as a
      percentage of the total milk volume was comparable. From this study it is
      concluded that behavioral and physiological responses, both in automatically and
      in conventionally milked cows, were relatively low and were typical for cows
      being milked. We therefore conclude that, as far as the welfare of the dairy cow
      during milking is concerned, automatic milking and conventional milking are
      equally acceptable.

PMID- 12512595
TI  - Physiological responses in thermal stressed Jersey cows subjected to different
      management strategies.
AB  - The effects of cooling and recombinant bovine somatotropin (rbST) on milk yield,
      reproductive performance, and health of Jersey cattle during summer thermal
      stress were measured for 2 yr. Cows were assigned to one of two groups based upon
      days in milk (DIM), parity, and genetic index. Year 1 and year 2 control cows (n
      = 143, n = 183, respectively) were housed in a pen with only shades. Cooled
      treatment cows each year (n = 142, n = 180) were housed with a spray and fan
      system for evaporative cooling. Cows were assigned at various days postpartum,
      not before d 63, coincident with commencement of rbST injections. One half of
      cows in each group received rbST on d 63 postpartum. Cows were assigned to the
      shade trial ranging from d 63 to 190. Cooled versus noncooled DIM were similar at
      the start of the trial. Trials began on July 1, 1999, and July 1, 2000, and
      concluded on September 30, 1999, and September 25, 2000. The ANOVA of daily milk
      weight data was conducted utilizing a 2 x 2 factorial design with cooling and
      rbST treatments as main effects. Cooling in combination with rbST increased milk
      yield compared with no cooling and no rbST for 1999 and 2000 (25.5 versus 21.8
      kg/d, and 23.7 versus 20.5 kg/d, respectively). In general, cooling improved
      health and reproductive performance.

PMID- 12512596
TI  - Factors influencing fertility of Holstein dairy cows: a multivariate description.
AB  - Eighty-two multiparous cows of high and low genetic merit were fed one of two
      isonitrogenous (19.3% crude protein), isoenergetic (11.3 MJ of metabolizable
      energy) diets that differed in ratio of rumen-undegradable protein to rumen
      degradable protein. Factors that influenced reproductive performance were
      investigated using logistic regression and survival analysis. Significant
      associations were identified between reproductive performance and indicators
      associated with nutrient balance. Cows with higher dry matter intake were more
      likely to show signs of estrus at first ovulation and to become pregnant by d 150
      of lactation. Increased ratio of plasma glucose to 3-hydroxybutyrate was
      associated with a greater probability of estrous expression at first ovulation.
      Concentrations of plasma cholesterol were positively associated with expression
      of estrus at first ovulation, interval from calving to conception, and likelihood
      of conception and pregnancy. Greater concentrations of nonesterified fatty acids
      in plasma were associated with a lower probability of conception by d 150 of
      lactation. Increased yield of fat-corrected milk during early lactation was
      negatively associated with expression of estrus at first ovulation and
      probability of pregnancy by d 150 of lactation. Cows of high genetic merit were
      less likely to show signs of estrus at first ovulation. Cows fed the high rumen
      degradable-protein diet that also lost more body weight during early lactation
      were less likely to conceive at first service and to have a prolonged interval
      from calving to conception. Continued selection for increased production of milk
      and a more negative nutrient balance during early lactation may reduce
      reproductive performance particularly for cows fed high concentrations of rumen
      degradable protein.

PMID- 12512597
TI  - Extending the postpartum anovulatory period in dairy cattle with estradiol
      cypionate.
AB  - Estradiol cypionate (ECP), a long-acting estrogen, has been used therapeutically
      in early postpartum (PP) dairy cows. In experiment 1, effects of ECP on
      circulating reproductive hormones, cyclicity, and ovarian function in early PP
      dairy cows were investigated. Lactating Holsteins received 10 mg of ECP (ECP; n =
      17) or placebo (CON; n = 16) on d 7 PP. Serum and ultrasound data were acquired
      from 5 to 90 d of lactation. Compared to CON, ECP cows had greater serum
      estradiol for 10 d and lower serum FSH for 15 d posttreatment. After ECP, the
      appearance of follicles > or = 10 mm and time to first ovulation were delayed.
      Nevertheless, by 90 d PP, normal estrous cycles were found in only 50% of CON
      versus 88% of ECP cows. Primiparous, but not multiparous, cows receiving ECP had
      higher milk yields. Experiment 2 investigated effects of ECP on reproduction and
      milk production on a commercial dairy. Cows were blocked by parity and randomized
      to three treatments: 0 (n = 85), 4 (n = 85), or 10 (n = 86) mg of ECP on d 5 to 8
      PP. Data included cycling status (two ultrasound examinations at 30 to 33 d PP
      and 7 d later), individual reproduction records, and daily milk yields from 10 to
      90 d PP. In primiparous cows, ECP had no significant effects on ovulatory status
      or milk yields. By 40 d PP, a greater percentage of multiparous cows receiving 10
      mg of ECP remained anovulatory compared with those receiving 0 or 4 mg. Milk
      yields were highest for multiparous cows receiving 4 mg of ECP, intermediate for
      the 10-mg dose, and lowest for controls. Lower conception was observed in
      multiparous cows receiving 4 mg of ECP. In summary, ECP delayed time to first
      ovulation particularly in multiparous cows, an effect associated with observed
      inhibition of circulating FSH. Milk yield responses to ECP were inconsistent
      within parity groups across the two experiments.

PMID- 12512598
TI  - The efficacy of intramammary tilmicosin at drying-off, and other risk factors for
      the prevention of new intramammary infections during the dry period.
AB  - The objective of this study was to compare the efficacy of an intramammary
      infusion, containing tilmicosin phosphate, to an infusion of a negative control
      intramammary placebo for preventing new intramammary infections (IMI) during the
      dry period. Cows were enrolled from 24 dairy herds from three geographical
      regions of Canada. Data from 248 cows and 938 bacteriologically negative quarters
      at drying-off are summarized. Overall, the rate of new IMI during the dry period
      was 16.7% of quarters. The new infection rates for quarters that received
      intramammary tilmicosin compared with the intramammary placebo were 14.4 and
      19.4%, respectively. The majority of new IMI was caused by coagulase-negative
      staphylococci (49%) and environmental streptococcal organisms (26.8%). The
      probability for quarters to develop new IMI in the dry period was significantly
      increased when cows had higher milk production before drying-off (P = 0.04), when
      cows had longer dry periods (P = 0.02), and when dry cows were housed in tie
      stall barns (P = 0.002). Higher parity cows and those that had a linear score
      somatic cell count (SCC) above 4 on the last DHI test were also at increased risk
      for new IMI (P < 0.10). Administration of intramammary tilmicosin appears to be
      an efficacious therapy for prevention of new IMI; however, there is currently no
      approved intramammary formulation of this product available. Use of blanket dry
      cow antibiotic therapy compared to selective dry cow therapy, as well as the
      importance of identifying risk factors and managing the environment of dry cows
      are discussed.

PMID- 12512599
TI  - Effects of BST on oviductal and uterine genes encoding components of the IGF
      system in lactating dairy cows.
AB  - Lactating Holstein cows, averaging 80 d in milk, were used to examine effects of
      exogenous bovine somatotropin (bST) on oviductal and uterine genes encoding
      components of the insulin-like growth factor (IGF) system. About 12 h before
      expected ovulation in an Ovsynch protocol, cows were assigned randomly to receive
      bST (500 mg; n = 11) or serve as untreated controls (n = 10). Cows that ovulated
      (n = 9 bST, 8 control) were divided within treatment to be sacrificed on d 3 or 7
      postovulation. Samples of oviductal and intercaruncular endometrial tissue from
      oviducts and uterine horns ipsilateral to the corpus luteum (CL) were collected
      and immediately frozen at -80 degrees C for subsequent mRNA analyses. Northern
      blots revealed mRNAs for IGF-II, IGF-binding protein-2 (IGFBP-2), and IGFBP-3 in
      all oviductal and endometrial tissues. Significant amounts of IGF-I and growth
      hormone receptor-1A (GHR-1A) mRNAs were detected in uteri but not in oviducts.
      The bST treatment had no effect on amount of IGF-I mRNA transcript in uterine
      endometrium. The mRNA encoding IGF-II was induced by bST in oviducts collected on
      both d 3 and 7 but was down-regulated in endometrium on d 7. Transcript of IGFBP
      2 mRNA was greater in endometrial than oviductal tissues and did not differ
      between treatments. Both oviductal and endometrial IGFBP-3 mRNA concentrations
      increased between d 3 and 7 postovulation, with a tendency for greater
      endometrial IGFBP-3 mRNA in bST-treated cows on d 7. On d 7, concentrations of
      endometrial GHR-1A mRNA were 30% lower in bST-treated cows. Results indicate
      complex and tissue-specific regulation of the uterine IGF system components by
      exogenous bST. Some of those biological responses to bST may be important in
      early development of bovine embryos.

PMID- 12512600
TI  - Blood and milk neutrophil chemiluminescence and viability in primiparous and
      pluriparous dairy cows during late pregnancy, around parturition and early
      lactation.
AB  - Extensive studies have shown the polymorphonuclear leukocytes (PMN) dysfunction
      inextricably links to parturition. To investigate the effect of parity on PMN
      function, phorbol 12-myristate 13-acetate (PMA) stimulated luminol-amplified
      chemiluminescence (CL) and viability of blood and milk PMN were investigated in
      primiparous and pluriparous dairy cows during periparturient period. The CL
      kinetics of blood and milk PMN and hematological profiles were also assessed.
      Milk PMN CL was always lower than blood PMN CL. Blood and milk PMN CL and milk
      PMN viability were significantly higher in primiparous cows throughout the study.
      Blood PMN CL in pluriparous cows showed a sharper decrease. Both in pluriparous
      and in primiparous cows, minimal blood PMN CL appeared at periparturient day
      (PPD) 2. After PPD 7, blood PMN CL recovery rate was faster in primiparous cows.
      Milk PMN CL was minimal at PPD 2 in both groups. Whereas no changes were observed
      in blood PMN viability, the viability of milk PMN in primiparous cows was
      substantially higher than in pluriparous cows. The number of circulating
      eosinophils and immature neutrophils was substantially higher in primiparous cows
      throughout the study. The CL kinetics of blood PMN at PPD -2 and 2 and of milk
      PMN at PPD 2 exhibited different responses to PMA, with higher intensity and
      durability, peaking and subsiding more slowly in primiparous dairy cows. The
      pronounced reduction in PMN CL and viability in milk PMN of pluriparous cows may
      be involved in the underlying mechanisms that make these animals more susceptible
      to periparturient infectious diseases.

PMID- 12512601
TI  - Evidence for a local effect of leptin in bovine mammary gland.
AB  - On average, high-energy diets promoting body growth rates above 1 kg/d before
      puberty impair mammary development by 15 to 20% in cattle. We hypothesized that
      leptin, a protein produced by adipocytes, mediates the inhibitory effect of high
      energy diets on mammary development. Therefore, our objectives were to determine
      the effect of leptin on mammary epithelial cell proliferation, and the
      distribution of mRNA for two leptin receptor isoforms in prepubertal bovine
      mammary glands and other peripheral tissues. Addition of leptin to culture media
      containing either 5 ng/ml of insulin-like growth factor-I (IGF-I) or 1% fetal
      bovine serum decreased DNA synthesis of a bovine mammary epithelial cell line
      (MAC-T) in a dose-dependent manner. The minimal doses of leptin that decreased
      IGF-I- and fetal bovine serum-stimulated cell proliferation were 64 and 1 ng/ml,
      respectively. In addition, we determined that MAC-T cells and isolated bovine
      mammary epithelial cells express the long form of leptin receptor (Ob-Rb) mRNA.
      Ob-Rb mRNA was detected in all bovine tissues examined. In contrast with reports
      on other species, mRNA expression of the short form of leptin receptor (Ob-Ra)
      was detected only in bovine liver, pituitary body, and spleen. These results
      support the concept that leptin mediates the inhibitory effect of high-energy
      diets on mammary development.

PMID- 12512602
TI  - Responses to tail docking in calves and heifers.
AB  - The primary objective of this study was to determine the behavioral and
      physiological effects of tail banding and atrophy using rubber rings 2 to 4 mo
      before first parturition in dairy heifers either with or without the use of
      epidural anesthesia. The secondary objective was to determine behavioral
      responses to tail banding using rubber rings in calves 7 to 42 d of age.
      Preparturient heifers (n = 24) were randomly assigned to one of four treatment
      groups: 1) tails were cleaned and handled; 2) tails were cleaned, handled, and an
      elastrator band was applied to the tail; 3) an epidural was administered 15 min
      before cleaning and handling; and 4) an epidural was administered 15 min before
      application of an elastrator band. Behavioral observations and physiological
      responses were collected for 6 wk. Additionally, behavioral responses to tail
      banding were recorded for 10 d on Holstein heifer calves that were 1 to 6 wk of
      age (n = 40). No significant differences in behavior were observed among
      treatment groups of preparturient heifers at any time during the 6-wk observation
      period. Preweaned calves that were 21 to 42 d of age demonstrated significantly
      more restlessness after application of tail bands compared to younger calves or
      control calves of the same age. Plasma cortisol values of preparturient heifers
      remained within limits previously described for nonstressed animals and no
      significant differences were detected among groups. Hematological values remained
      within the reference values for cattle, and there were no significant differences
      between groups except for relatively more eosinophils in the heifers that
      received epidurals. No significant differences in heart rate or body temperature
      were detected among groups.

PMID- 12512603
TI  - Effect of copper source and level on the rate and extent of copper repletion in
      Holstein heifers.
AB  - The objective of this study was to evaluate the rate and extent of Cu repletion
      in Holstein heifers using two Cu sources (organic and inorganic) at two levels
      (15 and 30 mg/kg). An additional repletion treatment included a Cu oxide bolus.
      Heifers (n = 50) were individually fed a total mixed ration fortified with S and
      Mo at 0.40%, and 15 mg/kg of dry matter of the total diet, respectively. After
      111 d of depletion, heifers were stratified by liver Cu concentration and
      randomly allotted to one of five repletion treatments. Four treatments consisted
      of feed sources of Cu (feed-Cu), 1) CuSO4 at 15 mg/kg; 2) CuSO4 at 30 mg/kg; 3)
      Availa-Cu at 15 mg/kg; and 4) Availa-Cu at 30 mg/kg. Availa-Cu is an organic Cu
      source that produces a Cu-amino acid complex. A fifth treatment, consisting of an
      intraruminal bolus (IB), provided a single dose of 25 g of CuO needles. Repletion
      treatments were delivered in the same total mixed ration without supplemental S
      and Mo. Copper status was assessed in blood and liver samples collected on 14-d
      intervals for 70 d. Irrespective of treatment, all heifers increased in body
      weight during the repletion period. Liver Cu increased in each feed-Cu treatment
      over time. Heifers treated with an IB reached a peak in liver Cu concentration
      (165.5 mg/kg) on d 28. Mean liver Cu concentrations were higher in heifers
      receiving 30 mg/kg of Cu compared with heifers receiving 15 mg/kg of Cu. Red
      blood cell superoxide dismutase (SOD) activity was higher (P < 0.001) in heifers
      receiving CuSO4 than Availa-Cu (0.98 vs 0.87 U). Also, SOD activity was higher
      when heifers were supplemented with 30 vs 15 mg/kg Cu (0.98 vs 0.87 U). Heifers
      receiving the Cu IB had higher SOD activity than heifers receiving feed-Cu
      sources (1.03 vs 0.92 U). Plasma ceruloplasmin concentration was higher (P <
      0.001) in IB-treated heifers vs. other treatments. No differences in plasma
      ceruloplasmin were detected for feed-Cu source or level. These results indicate
      that all Cu sources evaluated in this study elevated Cu status of depleted
      heifers, particularly when provided at higher dietary levels.

PMID- 12512604
TI  - Effects of a subacute ruminal acidosis model on the diet selection of dairy cows.
AB  - Two experiments were conducted to study the effects of a subacute ruminal
      acidosis (SARA) model on diet choice in dairy cows. In the first experiment, 25%
      of the ad libitum dry matter intake (DMI) of the total mixed ration (TMR) was
      replaced with wheat-barley pellets (WBP, 50% ground wheat, 50% ground barley).
      Rumen pH was measured continuously via in-dwelling probes in 4 mid to late
      lactation cows. This diet change reduced rumen pH by 0.14 +/- 0.02 pH units (mean
      +/- SE) and increased time below pH 6.0, from 319 +/- 36 min(-1) to 641 +/- 36
      min(-1). Hence, the nutritional model successfully induced SARA. The second
      experiment determined if inducing SARA increases the feed preference for long
      alfalfa hay compared with alfalfa pellets. The 2 wk of inducing SARA were
      separated by 1 control wk. Four cows on either SARA and control diets were given
      a choice of 2 feeds, 2 times per d, for 30 min. The preference ratios (PR =
      Amount of Hay consumed/Amount of Hay + Pellets consumed) for alfalfa hay during
      two SARA weeks was greater (0.85 +/- 0.03) compared with the control week (0.60
      +/- 0.03). In SARA weeks, average rumen pH was 0.23 +/- 0.03 units lower, and
      time below pH 6.0 and 5.6 was higher compared to control. These results suggest
      that when given a choice of feeds, dairy cows alter their diet selection to
      attempt to attenuate SARA.

PMID- 12512605
TI  - Estimation of energy balance at the individual and herd level using blood and
      milk traits in high-yielding dairy cows.
AB  - This study aimed to estimate individual and herd-level energy balance (EB) using
      blood and milk traits in 90 multiparous high-yielding Holstein cows, held on a
      research farm, from wk 1 to 10 postpartum (p.p.) and to investigate the precision
      of prediction with successively decreased data sets simulating smaller herd sizes
      and with pooled samples. Dry matter intake, milk yield, and BW were measured
      daily from parturition through wk 10 p.p. Milk composition was determined 4 times
      per week, and milk acetone was measured weekly. Blood samples for the
      determination of metabolites, hormones, electrolytes, and enzyme activities were
      taken weekly from wk 1 to 10 p.p. between 0730 and 0900. Body condition scores
      and ultrasonic measurements of backfat thickness and fat depth in the pelvic area
      were evaluated in wk 1, 4, and 8 p.p. Concentrations of glucose, cholesterol,
      urea, insulin, insulin-like growth factor-1, triiodothyronine, and thyroxine (T4)
      in blood plasma and of lactose and urea in milk were positively correlated with
      EB, whereas concentrations of nonesterified fatty acids (NEFA), creatinine,
      albumin, beta-hydroxybutyrate, and growth hormone and enzyme activities in blood,
      and concentrations of fat, protein, fat:lactose ratio, and acetone in milk were
      negatively correlated with EB. Leptin concentration was not correlated to EB over
      the first 10 wk p.p. To estimate EB linear mixed-effects, models were developed
      by backward selection procedures. The most informative traits for estimation of
      EB were the fat:lactose ratio in milk and NEFA and T4 concentrations in blood.
      The precision of estimation of EB in individual cows was low. Using blood in
      addition to milk traits did not result in higher precision of estimation of herd
      level EB, and decreasing sample sizes considerably lowered the precision of EB
      prediction. Estimation of overall mean herd-level EB over the first 10 wk p.p.
      using pooled samples was precise even with small sample sizes, but does not
      consider the level of EB in particular weeks. In conclusion, estimation of herd
      level EB at individual weeks using milk traits only has practical implication
      with herd sizes of > or = 100 cows if calving is highly seasonal and of or = 400
      cows if calving is uniformly distributed. Using blood in addition to milk traits
      does not improve precision of estimation of herd-level EB, regardless of sample
      size.

PMID- 12512606
TI  - Effect of a direct-fed fibrolytic enzyme formulation on nutrient intake,
      partitioning, and excretion in early and late lactation Holstein cows.
AB  - The effect of a fibrolytic enzyme formulation on N and P intake, partitioning,
      and excretion was evaluated in dairy cows in early and late lactation. Twelve
      lactating Holstein cows (6 early lactation, 6 late lactation) were fed diets with
      or without the enzyme formulation in a switchback design with three, 4-wk
      periods. Diets for the early lactation group contained 45% forage, and late
      lactation diets contained 61% forage. Cows fed diets containing the enzyme
      formulation gained more weight than those on the control diet; this weight gain
      with enzyme addition was greater in early lactation cows than in late lactation
      cows. The main effect of enzyme treatment did not significantly affect apparent
      digestibility or excretion of N and P, or retention of these nutrients in body
      tissue. Interactions observed between the effects of group (stage of lactation)
      and treatment indicated differences in the nature of the milk yield and manure
      excretion responses to enzyme treatment between early and late lactation cows.
      These interactions were due to numerical increases in milk yield, feces
      excretion, and N excretion in early lactation cows fed diets containing the
      enzyme formulation compared to control, and slight decreases in these measures in
      late lactation cows with enzyme addition. Cows fed diets containing a direct-fed
      fibrolytic enzyme formulation had increased body weight gain, but the effect of
      addition of the enzyme formulation on milk yield and manure nutrient excretion
      differed for early and late lactation cows.

PMID- 12512607
TI  - Effect of protein source on amino acid supply, milk production, and metabolism of
      plasma nutrients in dairy cows fed grass silage.
AB  - This study conducted according to a 4 x 4 Latin square with 28 d periods and four
      ruminally cannulated Finnish Ayrshire cows investigated the effect of protein
      supplements differing in amino acid (AA) profile and rumen undegradable protein
      content on postruminal AA supply and milk production. Mammary metabolism of
      plasma AA and other nutrients were also studied. The basal diet (Control; 13.4%
      crude protein) consisted of grass silage and barley in a ratio of 55:45 on a dry
      matter basis. The other three isonitrogenous diets (17.0% crude protein) were
      control + fishmeal (FM), control + soybean meal (SBM), and control + corn gluten
      meal (CGM). The protein supplements replaced portions of dry matter of the
      control diet maintaining the silage to barley ratio constant for all diets. Dry
      matter intake was limited to 95% of the preexperimental ad libitum intake and was
      similar (mean 19.8 kg/d dry matter) across the diets. Protein supplements
      increased milk, lactose, and protein yields but did not affect yields of energy
      corrected milk or milk fat. Milk protein yield response was numerically lowest
      for diet SBM. Protein supplements increased milk protein concentration but
      decreased milk fat and lactose concentrations. Microbial protein synthesis and
      rumen fermentation parameters were similar across the diets, except for an
      increased rumen ammonia concentration for diets supplemented with protein feeds.
      Protein supplements increased N intake, ruminal organic matter and N, and total
      tract organic matter, N, and neutral detergent fiber digestibilities. Protein
      supplements also increased N and AA flows into the omasum, with SBM giving the
      lowest and CGM the highest flows. This was associated with an unchanged microbial
      N flow and a higher undegraded dietary N flow. The omasal flows of individual AA
      reflected differences in total N flow and AA profile of the experimental diets.
      Differences in AA flows did not always reflect plasma AA concentrations. The
      results indicated that AA supply of dairy cows fed a grass silage-cereal diet can
      be manipulated using protein supplements differing in ruminal protein
      degradability and AA profile. Lower milk production response to SBM than that to
      FM and CGM appeared to be related mainly to lower N and AA supplies arising from
      a high ruminal protein degradability of SBM. Histidine appeared to be the first
      limiting AA for milk protein synthesis on the control diet. Mammary gland may
      regulate AA uptake according to requirements.

PMID- 12512608
TI  - Feed intake patterns, growth performance, and metabolic and endocrine traits in
      calves fed unlimited amounts of colostrum and milk by automate, starting in the
      neonatal period.
AB  - Feed intake, growth performance, and metabolic and endocrine traits were studied
      in male calves fed unlimited (GrAL; n = 7) amounts of colostrum for 3 d after
      birth and mature milk up to d 28 and were compared with calves fed commonly
      recommended amounts of colostrum and milk (GrRS; n = 7). Calves were fed by
      automates, and software was available to continuously register the time points
      and amounts of ingested feed up to 11 d of age. Body weight was measured on d 1,
      4, 7, 14, 21, and 28, and blood samples were taken on d 1, 2, 3, 7, 14, 21, and
      28 to measure several metabolites and hormones. Feed intake of calves fed GrAL
      increased from d 1 to 4, then remained stable and was always higher than for
      calves fed GrRS. Total visits (visits with and without milk intake) were higher
      for GrRS than GrAL, but visits with milk intake were comparable between groups
      and meal sizes per visit with milk intake were greater in GrAL than in GrRS. Body
      weight gain was greater in GrAL than in GrRS in wk 1, but not later. There were
      significant group differences in plasma concentrations of albumin (GrRS > GrAL),
      nonesterified fatty acids (GrRS > GrAL), cholesterol (GrRS > GrAL; d 28), insulin
      (GrAL > GrRS), and cortisol (GrRS > GrAL), but not of immunoglobin G, urea,
      glucose, triglycerides, growth hormone, and glucagon. In conclusion, calves fed
      ad libitum were capable of ingesting very large amounts of colostrum and milk,
      even during wk 1 of life, accompanied by a greater body weight gain in GrAL in
      the first week, whereas in GrRS, the high number of visits without feed intake
      indicate that these calves reached no repletion. Compared with calves provided
      restricted amounts of feed, calves with free access to colostrum and milk were
      characterized by reduced plasma concentrations of nonesterified fatty acids and
      by a transiently enhanced insulin and reduced cortisol status.

PMID- 12512609
TI  - Metaanalysis of input/output kinetics in lactating dairy cows.
AB  - The kinetics of dry matter intake, raw milk yield, milk fat yield, and body
      weight of 140 treatment groups of cows reported in 37 articles published between
      1959 and 1999 were collected in a database. The majority of these experiments
      were performed with Holstein-Friesian cows (primiparous: n = 51, multiparous: n =
      89). Animals were fed with forages and concentrates, offered separately (n = 98)
      or as a total mixed ration (n = 42). Empty body weight was calculated assuming
      that an increase of 1 kg in dry matter intake corresponded to an increase of 4 kg
      in gastrointestinal tract content. Each kinetic, denoted Y, was fitted with the
      model proposed by Grossman (1999) for raw milk yield. This model allowed the
      partitioning of the kinetic into three stages (early, middle, and late stages of
      lactation), each characterized by its own linear tendency. Kinetics were
      therefore summarized with parameter estimates of the model: the plateau value of
      Y in middle stage, the slopes of Y in early and late stages, and the weeks of
      start and end of the middle stage. The following additional variables were also
      calculated: the total increase of Y in early stage, the extrapolated value of Y
      at calving, and the persistency of Y defined as the duration of the middle stage.
      Variability of these parameters for each kinetic across treatment groups was
      examined through mixed models including the year of publication as covariate,
      parity as a fixed between-group factor, and trial as a random factor.
      Correlations between parameters within a Y-kinetic and between different Y
      kinetics were calculated by parity group and feed allocation system. Finally we
      propose predictive models which emphasized (1) the effect of empty body weight at
      calving on the depletion of empty body weight in early lactation, (2) the
      incidence of the kinetic of dry matter intake on the kinetic of raw milk yield in
      middle and late stages of lactation, and (3) the relationships between the
      kinetics of raw milk yield and milk fat yield in middle and late stages of
      lactation.

PMID- 12512610
TI  - Prediction of ammonia emission from dairy barns using feed characteristics part
      1: Relation between feed characteristics and urinary urea concentration.
AB  - Urinary urea concentration is an important predictor of NH3 emission from dairy
      barns. To reduce urinary urea concentration, accurate and precise prediction of
      urea concentration for different feeding regimes is a prerequisite. The objective
      of this research, therefore, was to predict urinary urea concentration of a cow
      using feed characteristics. To compute urinary urea concentration of a cow, we
      predicted: urine volume; urinary N excretion, using a regression or a mechanistic
      model; and the relationship between urinary urea concentration and urinary N
      concentration, which was derived from experimental data. Model results were
      validated using experimental data. Cows were fed one of nine diets, which was a
      combination of one of three rumen-degradable protein balances, and one of three
      roughage compositions. Each diet was repeated once. Measured parameters included
      herd, diet, and urine characteristics. Observed urinary urea concentration can be
      predicted with reasonable accuracy from existing models to predict urine volume
      and urinary N excretion using feed characteristics. The regression model
      predicted N excretion slightly better than the mechanistic model. In addition,
      input parameters required for the regression model are recorded at each dairy
      farm in The Netherlands. This regression model, therefore, can be used by animal
      nutritionists and producers to determine diets that result in a reduced NH3
      emission.

PMID- 12512611
TI  - Prediction of ammonia emission from dairy barns using feed characteristics part
      II: Relation between urinary urea concentration and ammonia emission.
AB  - Emission of NH3 from dairy barns can be reduced substantially by changing the
      cows' diet. Emission of NH3 is reduced most effectively when dietary changes
      result in a reduction of urinary urea concentration. The objective of this
      research was to predict NH3 emission from dairy barns for various diets, using
      feed characteristics, and climate, barn, and slurry related parameters. Model
      results were validated using experimental data. Cows were fed one of nine diets,
      which was a combination of three rumen degradable protein balances and one of
      three roughage compositions. Each diet was repeated once. Measured parameters
      included herd, diet, urine, slurry, barn and climate characteristics, and
      emission of NH3 from the barn. For a wide range of diets and barn conditions,
      observed NH3 emission from a dairy barn can be predicted accurately using a
      combination of existing nutrition-emission models. Accuracy of prediction
      improved considerably, however, when observed emissions during four diet
      treatments were omitted due to suspected technical failure of the emission
      measurement equipment. Results also show that NH3 emissions in common practical
      situations will range from about 3.3 to 16.3 kg per cow per 190 d. To reduce NH3
      emission in practice, farmers should maximize the diet's grass content, and at
      the same time, minimize its rumen degradable protein balance level. Currently,
      however, farmers need additional information to compose such a low-emission diet,
      which should fulfill also the intestine digestible protein and net energy
      lactation requirements of a cow.

PMID- 12512612
TI  - Effects of gossypol from cottonseed on hematological responses and plasma alpha
      tocopherol concentration of dairy cows.
AB  - The effects of feeding whole cottonseed (WCS) and bovine somatotropin (bST)
      administration on hematological responses and plasma alpha-tocopherol
      concentrations of lactating dairy cattle were examined. After parturition, multi
      and primiparous Holstein cows (n = 159) were assigned randomly to a 2 x 2
      factorial arrangement of treatments consisting of (0 or 15% WCS and 0 or 208 mg
      of bST injected every 2 wk starting within 7 d after calving. Blood samples were
      collected from a subset group of 64 cows at 14, 28, 42, and 56 d postpartum.
      Blood was collected from all cows (n = 159) at 75, 96 and 120 d postpartum. Blood
      samples were analyzed for alpha-tocopherol and total and (+)- and (-)-gossypol in
      plasma. Erythrocyte osmotic fragility, hemoglobin and hematocrit also were
      determined in blood. The mean concentrations of alpha-Tocopherol, total, and (+)-
      and (-)-gossypol were higher in cows fed WCS regardless of bST administration and
      plateaued by d 75 postpartum. Hematocrit and hemoglobin concentrations were not
      affected by treatments. Erythrocyte osmotic fragility was higher in cows fed WCS,
      but the increase was attenuated when bST was injected (diet x bST interaction).
      No clinical signs of gossypol toxicity were observed in the cows consuming the
      WCS.

PMID- 12512613
TI  - A pelleted combination of raw soyhulls and condensed corn steep liquor for
      lactating dairy cows.
AB  - An experiment was conducted to evaluate the effect of a pelleted combination of
      raw soyhulls and condensed corn steep liquor on performance and plasma
      metabolites when fed to replace a portion of the grain and forage in diets for
      lactating dairy cows. The raw soybean hull-corn steep liquor pellet (SHSL)
      contained 24.2% crude protein, 8.7% rumen undegradable protein, 28.9% acid
      detergent fiber, 36.7% neutral detergent fiber, and 2.5% ether extract (% of dry
      matter, [DM]). Eighteen multiparous Holstein cows were assigned to one of three
      diets in a replicated 3 x 3 Latin square design with 28-d periods. Cows were
      blocked by pretreatment body weight and energy-corrected milk (ECM) and assigned
      to control, SHSL (20.7% of diet DM), or pelleted raw soybean hulls ([PSH] 14.3%
      of diet DM). The SHSL product replaced 6.2% alfalfa hay, 3.7% corn silage, 6.6%
      corn, and 3.3% soybean meal (SBM), and 1.7% expeller SBM replaced solvent SBM in
      order to maintain dietary levels of rumen undegradable protein. PSH replaced 6.2%
      alfalfa hay, 3.7% corn silage, and 5.1% corn. Diet crude protein (%) and energy
      density (Mcal/kg NEL) were 16.6 and 1.64, 16.3 and 1.65, 17.1 and 1.63 for
      control, SHSL, and PSH, respectively. Cows fed PSH consumed more DM than cows fed
      control, with the intake of cows fed SHSL being intermediate. SHSL and PSH
      increased ECM, milk protein, and solids-notfat and showed higher concentrations
      of milk and plasma urea N and total alpha-amino N in plasma than the control
      diet. Furthermore, feeding SHSL tended to improve the ratio of ECM to DM intake.
      There was no effect of diet on concentrations of total essential and nonessential
      amino acids in plasma. These production data suggest SHSL can replace a portion
      of the forage, grain, and SBM in diets for lactating dairy cows without
      decreasing lactational performance.

PMID- 12512614
TI  - Effects of cultivars on ensiling characteristics, chemical composition, and
      ruminal degradability of pea silage.
AB  - A study was conducted to determine the effects of cultivar on ensiling
      characteristics, chemical composition and ruminal nutrient degradability of pea
      (Pisum sativum L.) silage. The cultivars evaluated were Lenca (L), Carneval (C),
      and Delta (D). Peas were field-grown and forage was harvested and ensiled in mini
      silos for 0, 2, 4, 8, 16, and 70 d. The ensiled forage of all cultivars went
      through a rapid fermentation with a sharp reduction in pH during the first 2 days
      of ensiling. Extensive proteolysis took place between 0 and 2 d as indicated by a
      reduction in true protein and neutral detergent insoluble protein (NDICP) and an
      increase in nonprotein nitrogen. Chemical analysis of the 70 d silage showed that
      cultivar L contained higher neutral detergent fiber (NDF) and acid detergent
      fiber and lower starch levels than C and D. Crude protein was highest for C
      (20.5% DM), intermediate for D (19.0% DM) and lowest for L (17.9% DM).
      Distribution of protein fractions showed that L contains lower soluble protein
      and higher NDICP levels than the other two pea cultivars. However, no difference
      in acid detergent insoluble protein levels was observed between the three
      cultivars. Results of the in situ incubation experiment indicated that L had
      lower ruminal DM (69.2 vs 74.0%) and CP (84.1 vs 90.6%) degradabilities than C or
      D. However, ruminal degradability of NDF was similar among the three cultivars
      (average of 32.9%). It was concluded that chemical composition and ruminal
      nutrient degradability of pea silage are significantly influenced by cultivars.

PMID- 12512615
TI  - The proportion of the diet to which fibrolytic enzymes are added affects nutrient
      digestion by lactating dairy cows.
AB  - Eight lactating Holstein cows, four with ruminal cannulas, were used in a
      duplicated 4 x 4 Latin square design to investigate a fibrolytic enzyme product
      characterized by xylanase and cellulase activities (Promote N.E.T. Agribrands
      International, St. Louis, MO). The diet consisted of concentrate containing
      rolled barley and supplement, barley silage and alfalfa haylage (55% to 45% DM
      basis, forage to concentrate ratio) and differed in enzyme application: 1)
      control, 2) enzyme applied to concentrate (45% of TMR), 3) enzyme applied to
      supplement (4% of TMR), and 4) enzyme applied to premix (0.2% of TMR). All diets
      that were supplemented with the enzyme product delivered about 1.0 grams per cow
      per day. Digestibility of OM, NDF and ADF in the total tract was increased in
      comparison to the control when enzymes were added to the entire concentrate.
      Enzyme treatments that were applied to a smaller portion of the diet showed only
      numerical increases in digestibility over the control. However, there was an
      increase in microbial N synthesis for cows fed enzymes added to the premix. The
      effects of enzyme supplementation on milk production and composition were not
      statistically significant, but cows receiving the enzyme product added to the
      concentrate had a numerically higher FCM compared to the control cows. These
      results indicate that enzyme supplementation increases total tract digestibility
      of organic matter and fiber. The proportion of the diet to which the enzyme is
      applied must be maximized to ensure a beneficial response.

PMID- 12512616
TI  - Animal and dietary factors affecting feed intake during the prefresh transition
      period in Holsteins.
AB  - Parity, body condition score (BCS), and dry matter intake (DMI) data of 699
      Holsteins fed 49 different diets during the final 3 wk of gestation (prefresh
      transition period) were compiled from 16 experiments conducted at eight
      universities. The objectives of this study were to determine the effects of
      animal and dietary factors on DMI and to elucidate interactions between animal
      and dietary factors and among dietary factors on DMI during the prefresh
      transition period. Animal factors examined were parity and BCS, whereas dietary
      factors examined were rumen undegradable protein (RUP), rumen degradable protein
      (RDP), neutral detergent fiber (NDF), and ether extract (EE). DMI decreased 32%
      during the final 3 wk of gestation, and 89% of that decline occurred during the
      final week of gestation. Day of gestation, animal factors, and dietary factors
      accounted for 56.1, 19.7, and 24.2% of explained variation in DMI, respectively,
      and R2 of this linear multivariable model was 0.18. Cows had higher DMI than
      heifers. DMI decreased linearly as BCS, RUP, and NDF increased, decreased
      quadratically as EE increased, and increased quadratically as RDP increased.
      Moreover, the magnitude of DMI depression as animals approached parturition was
      affected by characteristics of animals and dietary nutrient composition. There
      were significant parity x EE, BCS x NDF, RUP x NDF, RDP x NDF, NDF x EE, and RUP
      x EE interactions on DMI. In conclusion, parity, BCS, and concentrations of
      organic macronutrients in diets affected DMI during the prefresh transition
      period, and the magnitude of DMI depression as animals approached parturition.

PMID- 12512617
TI  - Sulfur and chlorine play a non-acid base role in periparturient calcium
      homeostasis.
AB  - The increased risk of periparturient hypocalcaemia through offering high-K feeds
      in the precalving period has been reported previously. Two experiments
      (experiment 1 and 2) investigated the effect of KCl fertilizer on pasture mineral
      concentration, the dietary cation-anion difference (DCAD), and the subsequent
      effect of this on periparturient plasma and urine mineral status. Experiment 2
      examined the effect of precalving Mg source (MgO, MgSO4, and MgCl2) and
      postcalving Ca supplementation on the concentration of Ca and Mg in plasma and
      urine. Unexpectedly, pasture DCAD increased (P = 0.06) from 434 to 535 mEq/kg DM
      in experiment 1 as pasture K concentration decreased from 4.2 to 3.5%, primarily
      because of a corresponding and greater decrease in pasture Cl concentration (from
      1.9 to 1.3%). Plasma Ca or Mg concentrations were not affected by pasture K
      concentration. A linear decline (P < 0.10) in urine Mg suggested a decline in Mg
      absorption as pasture K increased. In experiment 2, pasture DCAD decreased (P <
      0.05) linearly from 403 to 350 mEq/kg DM as pasture K concentration decreased
      from 3.8 to 3.3%. However, precalving urine pH was not affected by the declining
      DCAD. Postcalving plasma Ca concentration was affected by precalving Mg source
      with MgSO4 > MgCl2 > MgO. Differences in acid-base balance do not explain the
      difference between Mg salts. These results indicate that precalving dietary S and
      Cl concentration plays an important role in Ca homeostasis, in addition to its
      role in acid-base balance. Supplementation with Ca postcalving increased plasma
      Ca concentration for 2 d postcalving. Milk production was not affected.

PMID- 12512618
TI  - Effects of a monensin controlled-release capsule or premix on attenuation of
      subacute ruminal acidosis in dairy cows.
AB  - The effects of monensin, administered either as a controlled release capsule
      (CRC) or a premix, on attenuating grain-induced subacute ruminal acidosis (SARA)
      and on ruminal fermentation characteristics in Holstein cows receiving a total
      mixed ration were investigated in two experiments. In both experiments, six
      multiparous, rumen-fistulated Holstein cows were used in a two-treatment, two
      period crossover design with 6-wk periods. In Experiment 1, treatments were
      either a monensin CRC or a placebo CRC. In Experiment 2, treatments were either a
      monensin premix or a placebo premix. In both experiments, at the beginning of wk
      4 SARA was induced in experimental cows for a 10-d period with a grain challenge
      model, and ruminal pH was measured continuously using indwelling pH probes. The
      administration of monensin either as a CRC or a premix had no effect on ruminal
      pH characteristics. Neither monensin CRC nor premix had an effect on ruminal
      volatile fatty acid concentrations, but reduced the acetate:propionate ratio.
      Monensin premix-treated cows were observed to have increased milk yield, largely
      as a result of a higher dry matter intake in monensin-treated cows compared to
      control cows. Milk fat content and yield were lower in monensin-treated cows
      compared to placebo-treated cows during SARA. In conclusion, there is no evidence
      that monensin was efficacious in raising ruminal pH during SARA under the
      conditions employed in this study.

PMID- 12512619
TI  - Effects of feeding diets based on silage from corn hybrids that differed in
      concentration and in vitro digestibility of neutral detergent fiber to dairy
      cows.
AB  - A dual-purpose hybrid and a hybrid selected for high neutral detergent fiber
      (NDF) concentration were harvested as corn silage. The dual-purpose silage (DPCS)
      had 42% NDF and 35.4% in vitro (30 h) NDF digestibility and the high fiber silage
      (HFCS) had 49% NDF and 40.1% in vitro NDF digestibility. Two diets (dry matter
      basis) had 45% DPCS or HFCS and 46% corn grain-based concentrate (dietary NDF was
      29 and 32%, respectively), a third diet had 33% HFCS and 58% corn-based
      concentrate (27% dietary NDF), and a fourth diet had 33% DPCS and 58% concentrate
      that contained soybean hulls (32% dietary NDF). All diets contained 9% alfalfa
      silage. Diets were fed to eight midlactation Holstein cows in a 4 x 4 Latin
      square with 28 d periods. No differences among treatments were observed for milk
      yield (34.1 kg/d), dry matter intake (23.7 kg/d), and yield and concentration of
      milk protein. Cows fed the diet with 33% HFCS tended to have lower milk fat
      percentage than cows fed the 45% DPCS diet. Total digestible nutrients (measured
      using total collection) tended to be lower for the 33% DPCS diet than for the 45%
      DPCS diet. In vivo digestibility of NDF tended to be lower for the 33% HFCS diet
      than the 45% DPCS diet, but digestibility of starch in the two diets with HFCS
      was higher than the 45% DPCS diet. The lack of any substantial differences in
      responses suggest that the HFCS was equal to the DPCS when fed at 45% of the diet
      dry matter (53.5% total forage). When HFCS replaced DPCS so that NDF was similar
      between diets, milk fat percentage was reduced and ruminal propionate was
      increased. Increasing dietary NDF by adding soybean hulls to a diet based on DPCS
      reduced digestibility of dry matter, organic matter, and protein, and resulted in
      lower energy balance than the 45% DPCS diet.

PMID- 12512620
TI  - Reduced levels of total leukocytes and neutrophils in Norwegian cattle selected
      for decreased mastitis incidence.
AB  - Two groups of Norwegian Cattle showing significant genetic differences in
      clinical mastitis susceptibility were examined for hematological changes at three
      stages of lactation. Blood samples were taken from 91 healthy Norwegian Cattle
      cows and heifers belonging either to a high protein yield group or to a low
      clinical mastitis group and analyzed for hematological properties and serum
      cortisol levels at three stages of lactation. All animals were free of
      intramammary infections at the time of sampling. All cows had increased total
      white blood cells, neutrophils, and neutrophil/lymphocyte ratio as parturition
      approached, with peak levels at parturition. Cows selected for low clinical
      mastitis had lower levels of total white blood cells and neutrophils compared
      with cows selected for high protein yield throughout all three periods. The
      difference was significant prepartum. Cows from the low clinical mastitis group
      also had lower neutrophil/lymphocyte ratios and lower serum cortisol levels than
      those in the high protein yield group. A significant positive correlation was
      found between cortisol and total white blood cells and neutrophils, respectively.
      We conclude that selection for lower mastitis incidence in the low clinical
      mastitis group is associated with a significant decrease in total white blood
      cells and neutrophils in blood prepartum. Results from the present study, and the
      genetic difference in mastitis incidence observed in the groups, indicates that
      increased leukocyte mobilization at certain stages of lactation may be associated
      with increased susceptibility to mastitis.

PMID- 12512621
TI  - Short communication: Identification and characterization of multiple splicing
      forms of bovine prochymosin mRNA.
AB  - Bovine prochymosin (bPC) is an inactive precursor of the milk clotting enzyme
      chymosin (EC 3.4.23.4), that is present in the abomasum of suckling calves. We
      investigated the pattern of bPC mRNA expression in the calf stomach tissues by RT
      PCR assay and sequence analysis of cloned RT-PCR products. We identified multiple
      isoforms appearing due to alternative splicing of bPC mRNA. Alternative mRNA
      forms were generated by skipping one to four full exons within the bPC gene.
      Various splicing events resulted in seven bPC transcripts, which are 99, 114,
      213, 237, 336, 351 and 450 nucleotides shorter compared to full-length mRNA.
      Analysis of amino acid sequences deduced from alternatively spliced mRNA
      sequences showed no amino acid transversions and no protein reading frame shift
      for any splice forms.

PMID- 12512622
TI  - Genetic relationships between lifetime profit and type traits in Spanish Holstein
      cows.
AB  - Genetic parameters and relationships were estimated for profit and type traits
      for Spanish Holstein cows. In this study, 46,316 cows with official production
      and type data from Navarra and Basque autonomous regions of Spain were used to
      calculate profit per cow and year of productive life. Data from 239 Basque
      Autonomous Region herds in year 1995 were considered to obtain average prices
      system for yield, meat, feeding, and housing costs. An average cow had a net
      profit of 78.56 euros per year of productive life, with 7334 kg of milk, 3.85
      lactations and 28.0 mo of age at first calving. Heritability of profit was 0.25.
      Genetic correlations between profit and almost all conformation traits were low
      to moderate, from 0.12 for leg side view to 0.37 for suspensory ligament while
      stature, body depth, and udder depth had close to zero correlations with profit.
      Significant quadratic relationships were found between breeding values for profit
      and feet and legs, foot angle, fore-udder attachment, rear-udder height and udder
      depth. The most influential type trait on profit adjusted for production was feet
      and legs. Animals with negative breeding values for legs were not less profitable
      than another with zero value, but positive values increased profit per cow and
      year with a quadratic and positive relationship. Other traits affecting profit
      out of production and longevity, such as fertility and mastitis, should be
      considered in future studies.

PMID- 12512623
TI  - Evaluating sire selection practices using lifetime net income functions.
AB  - Dairy farmers do not take full advantage of opportunities available for genetic
      improvement through use of artificial insemination, perhaps because economic
      advantages of good sire selection may not be fully recognized or understood. This
      study was undertaken to document differences between use of AI and non-AI bulls
      and to develop prediction equations to compare lifetime economic merit of future
      progeny from alternative sire selection policies. We describe the use of two
      methods of measuring lifetime economic merit, with and without adjustment for
      opportunity cost of a postponed replacement. Comparison of lifetime relative net
      income adjusted for opportunity cost on groups of cows sired by different kinds
      of bulls showed that daughters of proven AI bulls generated $148 and $120 more
      lifetime net income under fluid and manufactured milk market conditions than
      daughters of non-AI bulls. Daughters of proven AI bulls produced $60 more than
      daughters of AI young sires in progeny testing programs at the time of daughter
      conception. We developed prediction equations from combinations of genetic
      evaluations for production, productive life, SCS, and linear type traits on sires
      to predict lifetime relative net income of progeny produced from alternative sire
      selection strategies. Prediction equations explained 14 to 18% of variation in
      relative net income (not adjusted for opportunity cost), but herd and year of
      first freshening accounted for considerably more variation than did genetic
      evaluations on the sire of the cow. Finally, two independent data sets were used
      to develop and test predictions of lifetime relative net income adjusted for
      opportunity cost using genetic evaluations based on the eight traits included in
      the Merit indexes for the sire of each cow. Prediction equations from odd
      numbered herds were used to predict lifetime economic merit in even numbered
      herds and vice versa. Coefficients of determination ranged from 0.088 to 0.103
      and averaged 0.004 higher than prediction equations with Net or Fluid Merit.
      Accuracy of predictions showed that Net and Fluid Merit were robust and useful
      indexes that accurately identified bulls whose daughters generated highest
      lifetime economic merit.

PMID- 12512624
TI  - Detection of pleiotropic effects of quantitative trait loci in outbred
      populations using regression analysis.
AB  - In this paper a method is presented to determine pleiotropic quantitative trait
      loci (QTL) or closely linked QTL in an outbred population. The method is based on
      results from single-trait analyses for different traits and is derived for a
      granddaughter design. The covariance between estimated contrasts of grandsires
      obtained in single-trait regression analysis is computed. When there is no
      pleiotropic QTL, the covariance between contrasts depends on the heritabilities
      of the traits involved, the polygenic and environmental correlation between the
      traits, the phenotypic standard deviations, the number of sires per grandsire,
      and the number of daughters per sire. A pleiotropic QTL results in a covariance
      that deviates from this expected covariance. The deviation depends on the size of
      the effects on both traits and on the fraction of grandsires heterozygous for the
      QTL. When analyzing experimental data, the expected covariance and the confidence
      interval for the expected covariance can be determined by permutation of the
      data. A covariance outside the confidence interval suggests the presence of a
      pleiotropic QTL or a closely linked QTL. The method is verified by simulation and
      illustrated by analyzing an experimental data set on chromosome 6 in dairy
      cattle.

PMID- 12512625
TI  - Characterization of the DGAT1 gene in the New Zealand dairy population.
AB  - Recently, DGAT1 was identified as the gene that underlies the QTL for bovine milk
      production on chromosome 14. This study investigated the effect of the reported
      polymorphism in three dairy breeds in New Zealand. Statistically significant
      results were identified for milk fat, milk protein, and volume for Jersey and
      Holstein-Friesian breeds, and only milk volume for Ayrshires. The average allele
      substitution effects were 2 to 3 kg of protein and 120 to 130 l milk for both the
      Jersey and Holstein-Friesian breeds. For milk fat, the average allele
      substitution effect was 6 kg for Holstein-Friesians and 3 kg for Jerseys. In all
      breeds, where the polymorphism increased milk fat yield, it decreased milk
      protein yield and milk volume.

PMID- 12512626
TI  - Producer breeding objectives and optimal sire selection.
AB  - Information from an online survey of dairy producers was used to determine how
      important producers perceived three different objectives in the breeding problem.
      The objectives were: maximizing expected net merit of the progeny, minimizing the
      expected progeny inbreeding coefficient, and minimizing semen expenditure.
      Producers were asked to rank the three objectives and then to weight the
      importance of each objective relative to the others. This information was then
      used to determine weights to be used in a multiple-objective integer program
      designed to select individual mates for a herd of 76 Jersey cows with known
      genetic background and cow net merit. The results of the multiple-objective
      models show that rank and relative importance of producer objectives can affect
      the portfolio of sires selected. Producers whose primary objective was to
      maximize expected net merit had a range of average expected progeny net merit of
      $306 to $310, but the level of expected progeny inbreeding was from 6.99 to
      10.45%, with a semen cost per conception of $35 to $41. For producers who
      selected minimizing progeny inbreeding as the primary goal in their breeding
      programs, the range of inbreeding was from 6.11 to 6.60%, with lower net merit
      range of $274 to $301 and semen expenditure of $30 to $37 per conception. One
      producer selected minimizing semen cost as the primary objective. For that
      producer's portfolio, the semen cost was $27 per conception and net merit was
      $288, with a progeny inbreeding coefficient of 10.68%. The results of this
      research suggest that producer information and goals have a substantial impact on
      the portfolio of sires selected by that producer to attain these goals.

PMID- 12512627
TI  - Effect of milking frequency on DHI performance measures.
AB  - Increasing production by increasing milking frequency (MF) is a management option
      available to dairy producers. This study examined effects of MF and interactions
      with region and herd size on measures of herd performance. Dairy Herd Improvement
      (DHI) Holstein herd summary records (n = 10,754, 10,550, and 10,438) for the
      years 1998, 1999, and 2000 were classified by MF: two times a day (2X) milking vs
      three times a day (3X); herd size: small (< 250 cows) and large (> or = 250
      cows); and region: North and South. Percentage of herds milking 3X by year were
      7.0, 6.7, and 7.1. Rolling herd average milk production was 16, 16, and 15%
      higher for herds milking 3X than herds milking 2X for the respective years. Herds
      milking 3X in the North region outproduced herds milking 3X in the South region.
      Milk fat and protein percentages were lower for herds milking 3X during all 3 yr.
      Differences in energy-corrected milk production between herds milking 3X and
      herds milking 2X were 14.5, 13.4, and 13.4% during the respective 3 yr as a
      result of lower component percentages for herds milking 3X. Herds milking 3X had
      more days open and higher actual calving intervals than herds milking 2X.
      Services per pregnancy for herds breeding primarily by artificial insemination
      were higher for herds milking 3X than for herds milking 2X. Somatic cell scores
      and weighted somatic cell counts were lower for herds milking 3X than herds
      milking 2X. Herds milking 3X had a higher percentage of somatic cell scores in
      the low range (0 to 3) and a lower percentage in the high range (7 to 9). Mean
      percentages of cows entering and leaving the herd were higher for herds milking
      3X during all 3 yr.

PMID- 12512628
TI  - Day and night seasonal temperature differences for a naturally ventilated
      freestall barn with different stocking densities.
AB  - Temperature data were collected during three 28-d periods. Cold-season one-side
      occupied (CSOO), warm-season two-sides-occupied (WSTO), and cold-season two-sides
      occupied (CSTO) were used to determine day and night freestall barn temperature
      differences between north-side and south-side, east-end and west-end, and inside
      to outside of a naturally ventilated, curtain sided, noninsulated barn. Five
      sensors measured temperature every 15 min for 28-d periods beginning November 30,
      2000, July 9, 2001, and December 23, 2001. Stocking densities were 90 to 100% for
      CSOO south-side and 0% for CSOO north-side; 92 to 108% for WSTO south-side and 46
      to 74% for WSTO north-side; and 102 to 116% for CSTO south-side and 64 to 86% for
      CSTO north-side. Mean day temperatures (MDT) and mean night temperatures (MNT)
      were different for all within barn comparisons. Inside and outside MDT were
      different for cold-season periods. MDT differences between inside and outside
      were CSTO (6.27 degrees F) > CSOO (5.64 degrees F) > WSTO (-0.03 degrees F). MNT
      differences between inside and outside were CSTO (7.14 degrees F) > CSOO (5.76
      degrees F) > WSTO (1.32 degrees F). Absence of animals on one side of the barn
      during cold seasons decreased the average temperature difference between inside
      and outside approximately 1 degree F (day 0.63 degrees F, night 1.38 degrees F).
      South-side MDT and MNT were higher than the north-side for CSOO. MDT differences
      between north-side and south-side were CSOO (-2.71 degrees F) > CSTO (-1.22
      degrees F) > WSTO (-0.36 degrees F). MNT differences between north-side and south
      side were CSOO (-2.46 degrees F) > CSTO (-1.06 degrees F) > WSTO (-0.49 degrees
      F). The average temperature difference for the unoccupied side during cold
      seasons was almost 1.5 degrees F lower throughout the day than the fully stocked
      side (day 1.49 degrees F, night 1.40 degrees F). Stocking density was thought to
      be the major cause of differences between north-side and south-side. East-end and
      west-end mean temperatures were not different across seasons, therefore, future
      barn-temperature research with barns of similar characteristics may require only
      one sensor per side.

PMID- 12512629
TI  - Test for measuring the stretchability of melted cheese.
AB  - A test for measuring the stretchability of cheese was developed by adapting a
      texture-profile analyzer to pull strands of cheese upwards from a reservoir of
      melted cheese. Seven different cheeses were analyzed using the Utah State
      University stretch test. The cheeses were also analyzed for apparent viscosity
      with a helical viscometer, for meltability using a tube melt test, and for
      stretch using the pizza-fork test. Cheese was placed into a stainless steel cup
      and tempered in a water bath at 60, 70, 80, or 90 degrees C for 30 min before
      analysis. The cup was then placed in a water-jacketed holder mounted on the base
      of the instrument. A three-pronged hook-shaped probe was lowered into the melted
      cheese and then pulled vertically until all cheese strands broke or 30 cm was
      reached. This produced a stretch profile as the probe was lifted through the
      reservoir of melted cheese and then pulled strands of cheese upwards. Three
      parameters were defined to characterize the stretchability of the cheese. The
      maximum load, obtained as the probe was lifted through the cheese, was defined as
      melt strength (F(M)). The distance to which cheese strands were lifted was
      defined as stretch length (SL). The load exerted on the probe as the strands of
      cheese were being stretched was defined as stretch quality (SQ). There was a
      correlation between F(M) and apparent viscosity. There was also some correlation
      between SL measured by the fork test and SL when the cheese was tested at 90
      degrees C, but no correlation occurred at lower temperatures.

PMID- 12512630
TI  - Laryngology: what are the new frontiers?

PMID- 12512631
TI  - Perceived pitch of synthesized voice with alternate cycles.
AB  - Both in normal speech voice and in some types of pathological voice, adjacent
      vocal cycles may alternate in amplitude or period, or both. When this occurs, the
      determination of voice fundamental frequency (defined as number of vocal cycles
      per second) becomes difficult. The present study attempts to address this issue
      by investigating how human listeners perceive the pitch of alternate cycles. As
      stimuli, vowels /a/ and /i/ were synthesized with fundamental frequencies at 140
      Hz and 220 Hz, and the effect of alternate cycles was simulated with both
      amplitude- and frequency-modulation of the glottal volume velocity waveform.
      Subjects were asked to judge the pitch of the modulated vowels in reference to
      vowels without modulation. The results showed that (a) perceived pitch became
      lower as the amount of modulation increased, and the effect seems to be more
      dramatic than would be predicted by existing hypotheses, (b) perceived pitch
      differed across vowels, fundamental frequencies, and modulation types, that is,
      amplitude versus frequency modulation, and (c) the prediction of perceived pitch
      was best made in the frequency domain in terms of subharmonic-to-harmonic ratio.
      These findings provide useful information on how we should assess the pitch of
      alternate cycles. They may also be helpful in developing more robust pitch
      determination algorithms.

PMID- 12512632
TI  - Normative voice range profiles of untrained boys and girls.
AB  - Normative voice range profiles (VRPs) are calculated for a group of untrained
      boys and girls between 6 and 11 years based on 35 and 39 recordings,
      respectively. All individuals had healthy voices. These normative VRPs contain
      95% prediction intervals (PI) for both frequency and intensity. They are based on
      a series of mathematical transformations of the original individual VRPs in order
      to maintain in the normative VRPs the typical oval VRP shape including the dip
      between modal and falsetto register. The presented normative VRPs are directly
      applicable in the clinical practice of otolaryngologists and speech-language
      pathologists.

PMID- 12512633
TI  - Speaking fundamental frequency in monozygotic and dizygotic twins.
AB  - The speaking fundamental frequency (SFF) and the intraindividual variation of the
      SFF during the reading of a Dutch standard text were measured in 30 female
      monozygotic twins (MT) and 30 dizygotic twins (DT), aged 15-29 years. A control
      group was created that consisted of 30 nonrelated paired individuals of equal
      age. Studying the intrapair correlation coefficients it seemed that the SFF was
      similar to a greater degree in MT and to a lesser degree in DT, while there was
      no correlation at all in nonrelated peers. These results are compatible with a
      genetic basis for the SFF. On the other hand, the intraindividual variation of
      the SFF was highly similar in MT and in DT (but not in nonrelated peers), so that
      for this parameter it was not possible to discern the influences of genetic
      disposition and shared environment.

PMID- 12512634
TI  - Source characteristics of aged voice assessed from long-term average spectra.
AB  - This study is the first to investigate age-related changes in the source
      characteristics of dynamic speech using long-term average spectral analysis
      (LTAS). A total of 80 speakers divided equally by age and gender participated.
      All participants were healthy, active community members. From the first paragraph
      of the Rainbow Passage, spectral energy measurements were completed for all
      speakers at 50 frequency levels across the LTAS. In comparison with young women,
      elderly women demonstrated: (1) significantly higher spectral amplitude levels at
      the frequencies of 320, 6080, 6240, 6400, 6560, and 6720 Hz; (2) significantly
      lower levels at the frequencies of 3040 and 3200 Hz; and (3) a tendency toward
      higher levels at 160 Hz. These findings suggest that both young and elderly women
      demonstrate spectral features associated with breathy voice quality, while
      differing in the specific spectral regions in which breathiness is indicated.
      Elderly men demonstrated significantly higher spectral amplitude levels than
      young men at 160 Hz, as well as significantly lower levels at 1600 Hz. Findings
      for men provide acoustic support for previous laryngoscopic findings of an age
      related increase in the incidence of glottal gaps.

PMID- 12512635
TI  - Harmonics-to-noise ratio: an index of vocal aging.
AB  - Distinguishing between vocal changes that occur with normal aging and those that
      are associated with disease is an important goal of research in voice. Several
      acoustic measures have been used in an attempt to illuminate the integrity of the
      vocal mechanism, including harmonics-to-noise ratio (HNR), jitter, and
      fundamental frequency (F0). HNR is a measure that quantifies the amount of
      additive noise in the voice signal; jitter reflects the periodicity of vocal fold
      vibration. In this study, measures of HNR, jitter and F0 were used to compare
      vocal function in three groups of normally speaking women: young adults, middle
      aged adults, and elderly adults. Significant differences in HNR emerged between
      the elderly women and the other two groups. F0 differences were also apparent
      between the elderly group and the two younger groups; there were no significant
      differences in jitter between the three groups. HNRwas found to be a more
      sensitive index of vocal function than jitter. The significant lowering of HNR
      evident in t he elderly speakers may be attributable in part to medications taken
      by the majority of these elderly subjects.

PMID- 12512636
TI  - Airway considerations for professional singers--a survey of expert opinion.
AB  - The objective of this study was to survey physician experts in voice
      disorders/treatment to establish consensus guidelines for translaryngeal
      intubation (TLI) and tracheotomy when treating professional singers or other
      voice professionals. A written survey was sent to all physician members of the
      Voice Foundation seeking opinions/recommendations about route of TLI, duration of
      TLI before tracheotomy, size of endotracheal and tracheotomy tubes, and special
      interventions during patient care as these might differ between professional
      singers and nonsingers. Fifty-five percent of the physicians responded, of whom
      73% classified their experience in voice care as "extensive." A strong consensus
      (76%) favored a smaller endotracheal tube for singers (6-7 mm I.D. for males and
      6.0 mm I.D. for females) via the oral (46%) versus nasal (36%) route.
      Intubation/extubation by the most expert/experienced personnel was emphasized so
      as to minimize direct trauma to the larynx. While intubated, strong
      recommendations were made to suppress gastric acid production and to minimize
      motion of the endotracheal tube, including patient sedation. Preferences for an
      early tracheotomy (6 days) versus their usual time (10 days) were approximately
      equal (44% vs. 50%, respectively) and most respondents (69%) recommended the same
      size tracheotomy tube (8.0 mm I.D. for males and 6.0 mm I.D. for females) for
      singers and nonsingers. Post extubation/decannulation care emphasized voice rest,
      retraining, continued gastric acid suppression, and the possibility of direct
      laryngoscopy to assess post-TLI or tracheotomy injuries.

PMID- 12512637
TI  - Expiratory muscle training increases pressure support in high school band
      students.
AB  - An experiment to increase expiratory muscle strength for instrumentalists, using
      a high-intensity, low-repetition expiratory training method, was conducted with
      40 healthy high school band players. Subjects trained five days per week for 2
      weeks using four sets of six training breaths for a total of 24 training breaths
      with a spring-loaded pressure relief valve that provided an adjustable threshold.
      The training valve pressure was set at 75% of the subject's measured maximum
      expiratory pressure (up to 80 cm H2O). Results demonstrated that high-intensity,
      low-repetition expiratory exercises significantly increased expiratory pressure
      generating capacity in these subjects and the degree of the training effect was
      similar regardless of the instrument the band member played. The training effect
      occurred within 2 weeks of initiating expiratory muscle training. Thus, this
      simple method of expiratory-specific strength training is effective and efficient
      for increasing expiratory pressure support in high school band students and has
      possibilities of a respiratory support device for many high pressure generating
      purposes. The potential mechanisms of the training effect are discussed.

PMID- 12512638
TI  - The ChatterVox portable voice amplifier: a means to vibration dose reduction?
AB  - By speaking loudly for extended periods, teachers are vulnerable to laryngeal and
      voice changes associated with vocal fold "vibration overdose." Voice clinicians
      frequently recommend voice amplification ostensibly designed to reduce vibration
      dose and improve voice. However, there are few data regarding the degree of vocal
      loudness attenuation achieved by specific amplification devices. The purpose of
      this investigation was to examine the effectiveness of the ChatterVox Portable
      Voice Amplification System (Siemens Hearing Instruments) for reducing the sound
      pressure level (SPL) of a speaker's voice during a simulated classroom lecture.
      Ten participants were instructed to continuously read one of two phonetically
      balanced passages while amplified and unamplified. Voice intensity measurements
      were obtained at three inches from the mouth (i.e., mouth level) and at the back
      of a classroom in both amplified and unamplified conditions. When amplified with
      the ChatterVox, speakers experienced an average decrease in vocal intensity at
      mouth-level of 6.03 dB SPL (p < 0.002). Furthermore, an average increase of 2.55
      dB SPL (p < 0.038) at the back of the classroom was observed. Collectively, these
      results indicate that the ChatterVox amplification device reduced the speaker's
      vocal intensity level at the microphone, while it augmented the voice heard at
      the back of the classroom. By inference, this degree of vocal attenuation at
      mouth level should contribute to a desirable reduction in vibration dose, thus
      lowering the risk of vibration overdose.

PMID- 12512639
TI  - Acoustic analyses of developmental changes and emotional expression in the
      preverbal vocalizations of infants.
AB  - The nonverbal vocal utterances of seven normally hearing infants were studied
      within their first year of life with respect to age- and emotion-related changes.
      Supported by a multiparametric acoustic analysis it was possible to distinguish
      one inspiratory and eleven expiratory call types. Most of the call types appeared
      within the first two months; some emerged in the majority of infants not until
      the 5th ("laugh") or 7th month ("babble"). Age-related changes in acoustic
      structure were found in only 4 call types ("discomfort cry," "short discomfort
      cry," "wail," "moan"). The acoustic changes were characterized mainly by an
      increase in harmonic-to-noise ratio and homogeneity of the call, a decrease in
      frequency range and a downward shift of acoustic energy from higher to lower
      frequencies. Emotion-related differences were found in the acoustic structure of
      single call types as well as in the frequency of occurrence of different call
      types. A change from positive to negative emotional state was accompanied by an
      increase in call duration, frequency range, and peak frequency (frequency with
      the highest amplitude within the power spectrum). Negative emotions, in addition,
      were characterized by a significantly higher rate of "crying," "hic" and
      "ingressive vocalizations" than positive emotions, while positive emotions showed
      a significantly higher rate of "babble," "laugh," and "raspberry."

PMID- 12512640
TI  - Changes in children's voices: the effect of cognitive cues.
AB  - Variation in duration and frequency during two readings of each of four sentences
      by 15 normal 9- and 10-year-old children were compared. Instructions to the
      children included overt cues designed specifically to elicit durational and
      frequency changes. Children demonstrated increased sentence variability in their
      voices when they were cued. Specific key words in the four sentences were also
      analyzed and results indicated that semantic content in addition to parameter
      specific cognitive cues provided a significant effect. The male 9 and 10-year-old
      subjects showed less variability in "no cue" readings than the females, but
      showed a greater increase in voice change during the "cognitive cue" readings.
      Implications for theory and practice are discussed.

PMID- 12512641
TI  - Psychogenic voice disorders in performers: a psychodynamic model.
AB  - Psychogenic voice disorders are not infrequently encountered in the busy voice
      clinic. A clinician-friendly psychodynamic model and a multidisciplinary
      management approach are presented which have proven helpful for our voice team
      and our patients. In essence the formulation revolves around an "event"
      occurring, which may be either organic or psychological in nature. The ensuing
      dysphonia then leads to emotional consequences which in turn have physical
      consequences on the vocal tract. The situation can become reinforcing and illness
      behaviors develop. Elucidating this event/process to the patient improves the
      likelihood of a successful long-term outcome. The diagnostic and management roles
      of the various team members are discussed.

PMID- 12512642
TI  - Nonorganic habitual dysphonia and autonomic dysfunction.
AB  - The present study was designed to test the hypothesis that there is a relation
      between nonorganic habitual dysphonia and subjective experience of dysfunction of
      the autonomic nervous system (neurovegetative lability). Eighty-three patients
      (65 women and 18 men) with a nonorganic voice disorder and a matched control
      group answered a questionnaire of 46 questions. One question replicated in
      different terms and six nonrelevant questions point out that the inquiry forms
      were answered in a consistent way. It appears that female patients in all age
      categories with a nonorganic habitual dysphonia report significantly more
      autonomic symptoms and complaints than healthy controls. This hypothesis cannot
      be confirmed for the male subgroup.

PMID- 12512643
TI  - Laryngeal herpes: a case report.
AB  - Herpetic laryngitis is a rare inflammatory disease caused by herpes simplex or
      herpes zoster virus. The propensity for spreading along peripheral nerves and
      within the central nervous system, with frank herpetic meningoencephalitis, is a
      rare complication. We present one case of herpetic laryngitis by reactivation of
      varicella zoster, with central nervous system spreading, and discuss the relevant
      literature on the pathophysiology, diagnosis, evaluation, and management of this
      disease.

PMID- 12512644
TI  - The prevalence of hypopharynx findings associated with gastroesophageal reflux in
      normal volunteers.
AB  - Routine laryngeal examination of patients with otolaryngologic complaints often
      reveals findings thought to result from gastroesophageal reflux. The direct
      association between these mucosal findings and uncontrolled reflux is not well
      established. To begin exploring the specificity of tissue signs, 105 normal,
      healthy, adult volunteers were examined by routine video fiber-optic endoscopy
      for the presence of findings attributed to reflux disease. Medical conditions,
      lifestyle factors, and ENT complaints were surveyed to reveal potential airway
      irritants, while the study design attempted to eliminate silent reflux. The
      majority of subjects (86%) had findings associated with reflux and certain signs
      reached a prevalence of 70%. Prevalence was not affected by ENT complaint,
      smoking, alcohol, or asthma. Intraexaminer and interexaminer agreement
      information is provided. The traditional attribution of hypopharynx irritation
      signs to reflux is challenged; the need for improved diagnostic specificity is
      highlighted.

PMID- 12512645
TI  - Effects of tonsillectomy on speech spectrum.
AB  - Changes in the speech spectrum of vowels and consonants before and after
      tonsillectomy were investigated to find out the impact of the operation on speech
      quality. Speech recordings obtained from patients were analyzed using the Kay
      Elemetrics, Multi-Dimensional Voice Processing (MDVP Advanced) software.
      Examination of the time-course changes after the operation revealed that certain
      speech parameters changed. These changes were mainly F3 (formant center
      frequency) and B3 (formant bandwidth) for the vowel /o/ and a slight decrease in
      B1 and B2 for the vowel /a/. The noise-to-harmonic ratio (NHR) also decreased
      slightly, suggesting less nasalized vowels. It was also observed that the
      fricative, glottal consonant /h/ has been affected. The larger the tonsil had
      been, the more changes were seen in the speech spectrum. The changes in the
      speech characteristics (except F3 and B3 for the vowel /o/) tended to recover,
      suggesting an involvement of auditory feedback and/or replacement of a new soft
      tissue with the tonsils. Although the changes were minimal and, therefore, have
      little effect on the extracted acoustic parameters, they cannot be disregarded
      for those relying on their voice for professional reasons, that is, singers,
      professional speakers, and so forth.

PMID- 12512646
TI  - Multifocal tracheal chondromata.
AB  - Chondromata of the trachea occur rarely. There are only 10 prior case reports in
      the literature, all of which have been of unifocal chondromata. We present the
      first case report, to our knowledge, of multifocal tracheal chondromata in a
      patient with laryngopharyngeal reflux. Evaluation, diagnosis, and management are
      discussed.

PMID- 12512647
TI  - What is nonablative photorejuvenation of human skin?
AB  - Nonablative photorejuvenation has become an integral procedure in the emerging
      discipline of laser dermatologic surgery. The objective is to confine
      selectively, without any epidermal damage, thermal injury to the papillary, and
      upper reticular dermis leading to fibroblast activation and synthesis of new
      collagen and extracellular matrix material. The procedure results in minimal
      patient morbidity, no interference with lifestyle, and a low risk of
      complications, while providing a satisfying degree of rhytides reduction.
      Multiple devices have been studied and marketed for nonablative photorejuvenation
      of human skin. However, currently, nonablative photorejuvenation should not be
      considered an alternative to laser skin resurfacing. The skin surface is not
      removed or modified. What really occurs may be more accurately referred to as
      dermal "remodeling" or "toning" as a wound healing response is initiated and
      collagen regenerated. The narrow "therapeutic window" of laser-induced dermal
      heating and epidermal cooling must still be optimized so that effective
      treatments can be obtained routinely. Clinical verification of effective
      treatment parameters (irradiation wavelength, pulse structure, radiant exposure,
      cooling time) will be obtained through further human studies. Most importantly,
      understanding the relationship between the degree of dermal thermal injury and
      synthesis of new collagen and extracellular matrix material will be fundamental
      to predicting the clinical efficacy and limitations of nonablative
      photorejuvenation.

PMID- 12512648
TI  - Biophysics of nonablative dermal remodeling.
AB  - This article explores the physics of nonablative skin remodeling as well as the
      histologic sequelae. Although there have been several studies of nonablative skin
      remodeling, the exact mechanisms of action and thus the optimum device-specific
      parameters are not yet known. The article is divided into a discussion of the
      physics of laser-tissue interactions, followed by a review of the types of
      devices used for nonablative skin remodeling, and the histologic findings that
      follow treatment.

PMID- 12512649
TI  - Quantitative evaluation of nonablative laser technology.
AB  - A new method for treating facial rhytides and acne scars with nonablative laser
      and light source techniques has recently been introduced. Given the inherent
      limitations of photographic and clinical evaluation to assess subtle changes in
      rhytides and surface topography, new noninvasive, objective instruments were used
      to accurately assess the outcome of these procedures. This study measures and
      objectively quantifies facial skin by using 2 novel, noninvasive measuring
      systems after 3 to 5 treatment sessions with the 1,064 nm QS Nd:YAG laser in
      patients with photodamage and acne scarring. One system measures the skin surface
      topography and the other characterizes the biomechanical properties of the skin.
      Patients undergoing facial rejuvenation procedures were analyzed before and after
      therapy with a 32 x 32 mm in vivo three-dimensional microtopography imaging
      system (PRIMOS, GFM, Teltow, Germany). The imaging system projects light on to a
      specific surface of the skin with a Digital Micromirror Device (DMD; Texas
      Instruments, Irving, TX) and records the image with a CCD camera. Skin Surface
      microtopography is reconstructed using temporal phase shift algorithms to
      generate three-dimensional images. Measurements were taken at baseline, at
      various times during the treatment protocol, and then at 3 and 6 month follow-up
      visits. Silicone skin replicas (FLEXICO, Herts, England) were also made before
      and after the laser treatment protocol for comparison to in vivo acquisition.
      Skin stiffness and compliance were measured with the BTC-2000 (BTC 2000, S.R.L.I.
      Inc. Nashville, TN). This instrument measures the response of the skin during
      dynamic stress created by suction. An infrared targeting laser measures the
      vertical displacement of the skin during the cycle. Pressure and deformation are
      graphically displayed on the monitor and embedded biomechanical algorithms
      determine the aforementioned parameters based on the average of 3 repetitive
      cycles. Four sites on the face were analyzed and compared including the right and
      left cheek and the right and left forehead. Measurements were taken at baseline
      and then at 1-, 3- and 6-month follow-up visits. Skin roughness decreased 11%
      from baseline in the patient with photodamaged skin, while the patients with acne
      scarring showed a 33% improvement from baseline after 3 treatment sessions. Six
      months after the fifth treatment session, a 26% improvement in skin smoothness
      was documented in the patients with photodamaged skin, while a 61% improvement
      was recorded in the subject with acne scarring. Biomechanical analysis of the
      skin showed a 23% decrease in skin stiffness and a 30% increase in skin
      compliance at the 6-month follow-up in the patients with photodamage.
      Alternatively, the patient with acne scarring showed a 50% increase in skin
      stiffness, and a 30% decrease in skin compliance at the 6-month follow-up. Three
      dimensional in vivo optical skin imaging provided a rapid and quantitative
      assessment of surface topography and facial fine lines after multiple treatment
      sessions with a 1064-nm QS Nd:YAG laser, correlating with clinical and subjective
      responses. Biomechanical analysis provided technical understanding of structural
      changes in photodamaged skin and acne scarring following nonablative laser
      treatment. Future applications of these devices may include comparison of
      nonablative laser technology, optimization of treatment regimens, and objective
      evaluation of other aesthetic procedures performed by dermatologists.

PMID- 12512650
TI  - Are all infrared lasers equally effective in skin rejuvenation.
AB  - In an attempt to limit the prolonged postoperative healing associated with
      ablative laser skin resurfacing and in response to growing public interest in
      less invasive treatment modalities, nonablative laser and light source technology
      was developed. Over the past few years, several clinical and histologic research
      studies have been conducted to determine the relative efficacy of these
      nonablative systems. These systems stimulate dermal collagen remodeling using
      wavelengths and concomitant tissue cooling that limit injury to the epidermis,
      thereby minimizing or eliminating postoperative sequelae. While nonablative
      lasers do not supersede already established ablative laser technologies, they
      supplement the treatment armamentarium, making a wider range of treatment options
      available and enhancing the ability to correlate the needs of individual patients
      more closely with the specific advantages offered by a particular modality.

PMID- 12512651
TI  - Intense pulsed-light photorejuvenation.
AB  - Intense pulsed light photorejuvenation represents a novel mode of treatment of
      photodamaged skin. A broad-spectrum flashlamp (500-1200 nm) targets chromophores
      reversing pigmentation, vascular and pilosebaceous aberrations. Both cytokine
      mediated as well as thermally induced deep dermal remodeling may be achieved
      using the varied polychromatic wavelengths associated with this technology.
      Inflammatory dermatosis such as rosacea may also be addressed as well. A
      structural approach to non-ablative rejuvenation utilizing intense pulsed light
      is associated with high patient satisfaction and minimal adverse sequelae.

PMID- 12512652
TI  - Combination visible and infrared lasers for skin rejuvenation.
AB  - Noninvasive techniques for skin rejuvenation are quickly being established as a
      new standard in the treatment of mild rhytides and overall skin toning. Multiple
      laser wavelengths and modalities have been tried for this procedure with varying
      degrees of success. These lasers include 532 nm, 585 nm, 1064 nm, 1320 nm, 1450
      nm, and 1540 nm wavelengths. This study evaluates a combination technique by
      using a long-pulsed 532 nm potassium titanyl phosphate (KTP) laser and a long
      pulsed 1064 nm Neodynium:yttrium aluminum garnet (Nd:YAG) laser, both separately
      and combined, for noninvasive photorejuvenation and skin toning/collagen
      enhancement, and establishes efficacy and degree of success. A total of 150
      patients were treated with the long-pulsed KTP 532 nm (Aura; Laserscope, San
      Jose, CA) and long-pulsed Nd:YAG 1064 nm (Lyra; Laserscope) lasers both
      separately and combined. Patients included skin types I through V. The fluences
      varied between 7 and 15 J/cm2 at 7 to 20 ms pulse duration with a 2-mm handpiece,
      and 6 to 15 J/cm2 and 30 to 50 ms with a 4-mm handpiece for KTP. The Nd:YAG
      fluences were set at 24 to 30 J/cm2 for a 10-mm handpiece and 30 J/cm2 for a
      SmartScan Plus scanner (Laserscope, San Jose, CA). These energies were delivered
      at 30 to 65 ms pulse durations. All patients were treated at least 3 times and at
      most 6 times at monthly intervals, and were observed for up to 18 months after
      the last treatment. All 150 patients exhibited a mild to moderate degree of
      improvement in the appearance of rhytides, moderate degree of improvement in skin
      toning and texture, and great improvement in the reduction of redness and
      pigmentation. The KTP used alone was superior to the Nd:YAG laser in terms of
      results. The KTP and Nd:YAG laser combination was superior to either laser used
      alone.

PMID- 12512653
TI  - Are we ready? Thinking about the unthinkable.

PMID- 12512654
TI  - Standing up for dentistry.

PMID- 12512655
TI  - Chronic facial pain.

PMID- 12512656
TI  - Hormone replacement.

PMID- 12512657
TI  - Trigeminal nerve injuries.

PMID- 12512658
TI  - Have you experienced problems obtaining liability insurance?

PMID- 12512659
TI  - Use of HIV postexposure prophylaxis by dental health care personnel: an overview
      and updated recommendations.
AB  - BACKGROUND: The authors conducted a study on the use of postexposure prophylaxis,
      or PEP, for exposure to human immunodeficiency virus, or HIV, among dental health
      care personnel, or DHCP, enrolled in a surveillance system established by the
      Centers for Disease Control and Prevention, or CDC. They also discuss updated
      U.S. Public Health Service, or USPHS, recommendations for managing occupational
      exposures to HIV, as well as considerations for dentistry. METHODS: The authors
      analyzed occupational exposures reported by DHCP to the CDC to describe
      characteristics of the exposure (for example, type and severity), the source
      patient's HIV status and use of PEP. RESULTS: From June 1995 through August 2001,
      DHCP reported 208 exposures--199 percutaneous injuries, six mucous membrane
      exposures and three skin exposures--to the CDC. One-third of these percutaneous
      injuries were caused by small-bore hollow syringe needles, and most (66 percent)
      were moderate in depth. Nearly half the devices involved (46 percent) were
      visibly bloody at the time of injury. Per the criteria described in USPHS
      guidelines, one-half of the injuries were categorized as "less severe." Twenty
      four (13 percent) known source patients were HIV-positive; 14 had symptomatic HIV
      infection or a high viral load. In this study, three in four DHCP exposed to an
      HIV-positive source warranted a three-drug PEP regimen. Twenty-nine (24 percent)
      DHCP exposed to a source patient who subsequently was found to be HIV-negative
      took PEP; six took PEP for five to 29 days. No exposures resulted in HIV
      infection. CONCLUSIONS: Findings of this study are consistent with earlier
      reports indicating that the risk of HIV transmission in dental settings is low.
      Strategies such as rapid HIV testing of source patients and follow-up counseling
      may reduce unnecessary use of PEP. CLINICAL IMPLICATIONS: Dental practices should
      develop comprehensive, written programs for preventing and managing occupational
      exposures to blood.

PMID- 12512660
TI  - Updated USPHS guidelines for managing occupational exposures to HBV, HCV, and HIV
      and considerations for dentistry.

PMID- 12512661
TI  - Management of occupational blood exposures.

PMID- 12512662
TI  - Human mineralized bone in extraction sites before implant placement: preliminary
      results.
AB  - BACKGROUND: Bone loss after tooth extraction may prevent dental implant
      placement. Human mineralized bone grafts can be used to restore bone volume and
      allow for tooth replacement with dental implants. METHODS: The authors grafted 22
      sites in 18 patients with human mineralized bone after tooth extraction. They
      allowed molar sites 16 weeks for graft healing, placed the implants and restored
      them with a final crown after a four-month integration period. Single-rooted
      maxillary sites received implants and immediate placement of provisional crowns
      or underwent a delayed two-stage restoration approach. The authors used
      radiographs and clinical examinations to evaluate the results. RESULTS: All of
      the sites were restored successfully with a single-tooth implant restoration.
      Periapical radiographs indicated that the crestal bone levels were limited to the
      first thread of the implants or slightly coronal to the first thread of the
      implant. Clinical evaluation indicated excellent gingival health around the
      provisional and final restorations, without obvious gingival migration.
      CONCLUSIONS: The use of human mineralized bone may have significant potential to
      reconstruct missing bone resulting from tooth extraction and to preserve bone
      after tooth extraction. In addition, healed bone graft sites seem to be able to
      support immediate placement of a provisional crown and implant restorations.
      CLINICAL IMPLICATIONS: Patients who are having teeth extracted may become
      candidates for implant restorations when the sites are appropriately grafted to
      preserve and reconstruct bone volume, thus allowing for more options for
      reconstructing the missing tooth site.

PMID- 12512663
TI  - The air turbine and hearing loss: are dentists at risk?
AB  - BACKGROUND: Damage to the dentist's hearing because of the popularity of the air
      turbine has been the subject of many articles, but no conclusive proof has been
      given that the turbine is a health factor. OVERVIEW: The author provides a
      historical review of the literature regarding hearing loss among dentists.
      CONCLUSIONS: In light of the inconclusive results of the literature review, the
      author recommends that further studies be conducted.

PMID- 12512664
TI  - Early treatment of incipient carious lesions: a two-year clinical evaluation.
AB  - BACKGROUND: The purpose of this study was to quantify conservation of tooth
      structure and evaluate the efficacy of early treatment of questionable carious
      lesions in pits and fissures of posterior teeth using air abrasion followed by
      placement of preventive resin restorations. METHODS: Ninety-three patients with
      223 questionably carious teeth, mainly with darkly stained pits and fissures,
      were recruited from general dentistry clinics. After baseline evaluation, each
      tooth was randomly assigned to either an early treatment or control group. The
      authors used air abrasion to investigate the pits and fissures of teeth in the
      early treatment group. The teeth were sealed and restored with a flowable resin
      based composite. All teeth in both groups were examined at six-month intervals to
      clinically evaluate the quality of the restorations and the caries status of the
      control teeth. RESULTS: After two years, two of the 113 restorations in the early
      treatment group required further treatment because of penetrating stain at a
      margin. In the control group, 14 teeth required treatment because of caries. The
      mean weight of the impression material--a surrogate measure of volume of removed
      tooth structure--in preparations that extended into dentin in the early treatment
      group was 0.0260 grams compared with 0.0281 g in the control group. There was no
      statistically significant difference between the impression weights (P = .390).
      CONCLUSION: After two years of a proposed five-year study, the authors concluded
      that conservation of tooth structure was not substantiated by early treatment.
      CLINICAL IMPLICATIONS: Treating questionable carious lesions early may not
      conserve tooth structure.

PMID- 12512665
TI  - Injection pain of bupivacaine with epinephrine vs. prilocaine plain.
AB  - BACKGROUND: Prilocaine plain has been described in the literature as causing less
      pain on injection than bupivacaine with epinephrine, possibly because of the
      higher pH of the prilocaine anesthetic solution. METHODS: In a double-blind study
      design, 681 consecutive patients in a general dental practice received maxillary
      buccal infiltration, posterior palatal infiltration or inferior alveolar block
      injections, administered under clinical conditions by one of two dentists.
      Immediately after injection, patients rated the pain from each injection on a six
      point scale. The pain response was analyzed according to treating dentist,
      location of injection, patient's sex and anesthetic administered. RESULTS: The
      reported pain on injection of bupivacaine with epinephrine was significantly
      greater than that of prilocaine plain. Patients reported no significant
      difference in pain at different injection locations, except that palatal
      injections caused significantly more reported pain than did anterior maxillary
      infiltration, posterior maxillary infiltration or inferior alveolar block
      injections. CONCLUSIONS: Under clinical conditions, the injection of bupivacaine
      with epinephrine causes significantly more perceived pain than does the injection
      of prilocaine plain. Clinical Implications. Bupivacaine with epinephrine and
      prilocaine plain have certain advantages and disadvantages that should be
      considered before choosing an anesthetic for a dental procedure. A disadvantage
      of bupivacaine with epinephrine is that it produces more perceived pain than does
      prilocaine plain.

PMID- 12512666
TI  - The effect of electrical dental equipment on a vagus nerve stimulator's function.
AB  - BACKGROUND: Dental patients who have epilepsy with pharmacologically refractory
      seizures may be treated with an implanted pulse generator that electrically
      stimulates the left vagus nerve. The pulse generator functions like a cardiac
      pacemaker. Some electrical dental devices have been shown to cause
      electromagnetic interference with the function of cardiac pacemakers. The
      potential effect of similar dental equipment on vagus nerve stimulators is
      unknown. METHODS: Common electrical dental devices were operated at maximum power
      settings in close proximity to a representative vagus nerve stimulator. The
      author assessed any interference of the dental devices with the nerve stimulator
      function by observing oscilloscope tracings. RESULTS: Under the conditions of
      this evaluation, none of the dental devices tested altered the function of the
      vagus nerve stimulator. CONCLUSIONS: Some commonly used electrical dental devices
      may be used in close proximity to patients who have implanted vagus nerve
      stimulators without adverse effects on the nerve stimulator function. CLINICAL
      IMPLICATIONS: Dentists and dental hygienists may encounter patients with
      implanted vagus nerve stimulators, and they need to be cognizant of developments
      in the treatment of epilepsy. Under the conditions of this study, use of common
      dental electrical devices did not alter the function of a vagus nerve stimulator.
      The findings of this study, however, should not be generalized to all types of
      electrical dental or medical devices, as a recent report indicates that treatment
      with diathermy devices is contraindicated for patients with implanted nerve
      stimulators.

PMID- 12512667
TI  - Time-saving record keeping.

PMID- 12512668
TI  - Providing dental care for special patients: tips for the general dentist.
AB  - BACKGROUND: Nearly 20 percent of the U.S. population has some type of disability,
      with approximately 12 percent of the population considered to have severe
      disabilities. The provision of dental care to such patients requires
      consideration beyond routine approaches. OVERVIEW: This article discusses
      techniques, such as establishing a relaxing treatment environment, that can be
      used to accommodate special-needs patients in the general dental practice. It
      provides background information on the current special-needs population in the
      United States, and it describes the oral care approaches used in a residential
      care facility vs. a general dental practice. The article concludes with tips for
      integrating this special patient population into a general dental practice.
      CONCLUSIONS AND PRACTICE IMPLICATIONS: As the U.S. population with special needs
      increases, more general dentists are likely to find that such patients require
      their services. While the prospect of accommodating the needs of patients with
      disabilities may seem daunting initially, such treatment actually can be
      incorporated into a general dental practice easily. The practitioner treating
      patients with disabilities likely will find that he or she needs special
      equipment less than compassion and tolerance.

PMID- 12512669
TI  - Oral health status of rural adults in the United States.
AB  - BACKGROUND: Many sociodemographic indicators of oral health disparity in the
      United States have been documented. Rural residence, however, has not been
      researched thoroughly, though it has been considered to be a potential indicator
      of disparity. The authors conducted this study to present information on the
      effects of rural residence on oral health in the United States. METHODS: The
      authors conducted their analyses using data from adults aged 18 to 64 years from
      the 1995, 1997 and 1998 National Health Interview Surveys and the Third National
      Health and Nutritional Examination Survey, 1988-94. The authors present national
      estimates for various oral health status indicators including dental insurance
      coverage, unmet care needs, frequency of dental visits, caries experience and
      prevalence of edentulism by rural/urban residence. RESULTS: The authors found
      that adults living in rural areas were more likely to report having unmet dental
      care needs and were less likely to have had a dental visit in the past year
      compared with adults living in urban areas. The prevalence of edentulism among
      rural adults was 16.3 percent-almost twice that of urban adults. Caries
      experience also was more likely to be greater among adults residing in rural
      areas. CONCLUSIONS: Oral health disparities exist among U.S. adults living in
      rural and urban areas. Compared with urban residents, rural residents were less
      likely to report a dental visit in the past year and were more likely to be
      edentulous. PRACTICE IMPLICATIONS: By understanding the rural/urban differences
      in adult oral health status, practitioners, policy-makers and rural health
      advocates will have better information to use to promote activities that better
      meet the needs of rural adults in the United States.

PMID- 12512670
TI  - Oral care for patients with bulimia.
AB  - Various conditions cause rapid and debilitating erosion of teeth. One of the most
      common is bulimia, or the binge-purge syndrome. Dentists frequently encounter
      patients who have this problem. The dentist should confirm the possibility of
      bulimia, refer the patient to a competent eating-disorder clinic, counsel the
      patient about her or his condition and restore the patient's mouth to a state of
      health and esthetic acceptability. Dental treatment of such patients will vary
      depending on the severity of the erosion.

PMID- 12512671
TI  - HIPAA privacy regulations: new requirements for protecting patients' health
      information. Health Insurance Portability and Accountability Act.

PMID- 12512672
TI  - Panoramic and cephalometric extraoral dental radiograph systems.
AB  - The basic unit is the Orthopantomograph OP100, which is a computer-controlled
      extraoral imaging system capable of producing panoramic radiographs using either
      film or digital technology. This unit has automatic exposure control, automatic
      spine compensation, a patented V-shaped X-ray beam and a built-in quality
      assurance program. The OP100 is available with cephalometrics (the OC100 model),
      linear tomography (the Ortho Trans model), identification film marking (the Ortho
      ID model) and imaging software (the Ortho Zone and Ortho TMJ models). The
      addition of a cephalometric arm to the Orthopantomograph makes the unit an
      Orthoceph. The image receptor sizes are as follows: Panorama OP100: cassette 15 x
      30 centimeters; Cephalometric image receptor OC100: 24 x 30 cm, 18 x 24 cm, 8 x
      10 inches; Panoramic image receptor OP100D: CCD camera, image pixel size 90 x 90
      micrometers; Cephalometric image receptor OC100D: CCD camera, image pixel size 90
      x 90 microm.

PMID- 12512673
TI  - Panoramic imaging.

PMID- 12512674
TI  - For the dental patient... Eating habits that can harm teeth.

PMID- 12512675
TI  - From the Balint method toward profession-related supervision.
AB  - This paper focuses on Michael Balint's special application of psychoanalysis,
      originally conceived as a training of doctors. Then the attempt is made to
      discover indirectly, since Balint never described his method in context, what he
      thought mattered in terms of method. Besides Balint's own contributions, those of
      his own staff are also consulted as well as the cultural background of the
      Tavistock Clinic and the Tavistock Institute. Then the further developments of
      the Balint method in the German-speaking world are presented. At the center are
      the special features of the method: (a) the atmosphere, (b) the narrator's
      contribution, (c) listening and reactions of the members of the group, (d) the
      unconscious enactments in transference and countertransference and the mirror
      phenomena, respectively. Furthermore, the respective central points of reference
      are discussed from the viewpoint of communication science: (a) case, (b) group,
      and (c) institution. In conclusion and based on these foundations, the
      characteristics of the application of the Balint method in the form of a
      particular profession-related supervision are presented.

PMID- 12512676
TI  - The Balint movement worldwide: present state and future outlook: a brief history
      of Balint around the world.
AB  - Michael and Enid Balint began running seminars for GPs (family physicians) in
      London in the late 1950s. Balint groups were soon started in other countries
      leading to the formation of the International Balint Federation. This paper
      describes the activities of the Federation and surveys the health and strength of
      the Balint movement in different parts of the world. While formal Balint training
      seems unlikely to become part of the official curriculum in more than a few
      countries, Balint's ideas will continue to be influential.

PMID- 12512677
TI  - Understanding the dynamics of the patient-physician relationship: balancing the
      fiduciary and stewardship roles of physicians.
AB  - There has been growing concern about the effects on the patient-physician
      relationship of the increasing demands on physicians to balance their fiduciary
      and stewardship responsibilities, what has been called "double agency." Various
      authors have proposed ways to restore patient centeredness to the patient
      physician interaction. We have previously discussed the need to establish a
      patient-physician alliance to achieve this aim and to facilitate achieving this
      balance in mutual understanding. In this essay, we examine six concepts derived
      by Michael Balint from research seminars with primary care physicians. These six
      concepts are (a) the basic fault; (b) the physician's apostolic function; (c) the
      mutual investment company; (d) the drug "doctor"; (e) the deeper diagnosis; and
      (f) the conspiracy of anonymity. We believe these six concepts describe basic
      forces that shape the patient-physician relationship and allow for the
      development of an alliance between patients and physicians that can help preserve
      the essentials of the relationship.

PMID- 12512678
TI  - Three testimonies about meeting Michael Balint and his ideas.

PMID- 12512679
TI  - Excerpts of the correspondence of Michael and Alice balint with Olga, Ladislas,
      and Judith Dormandi.

PMID- 12512680
TI  - An interview with Michael Balint.

PMID- 12512682
TI  - To treat or not to treat? That is the question.

PMID- 12512683
TI  - Asymptomatic corneal staining associated with the use of balafilcon silicone
      hydrogel contact lenses disinfected with a polyaminopropyl biguanide-preserved
      care regimen.
AB  - PURPOSE: To compare subjective symptoms and signs in a group of individuals who
      wear silicone-hydrogel lenses on a daily wear basis while they sequentially used
      two differing care regimens. METHODS: Fifty adapted soft-lens wearers were fitted
      with a silicone-hydrogel lens material (PureVision, Bausch & Lomb). The lenses
      were worn on a daily wear basis for two consecutive 1-month periods, during which
      the subjects used either a Polyquad (polyquaternium-1) -based system or a
      polyaminopropyl biguanide (PHMB) -based system, using a double-masked,
      randomized, crossover experimental design. RESULTS: Significant levels of
      relatively asymptomatic corneal staining were observed when subjects used the
      PHMB-based system, with 37% of subjects demonstrating a level of staining
      consistent with a classical solution-based toxicity reaction. Only 2% of the
      subjects exhibited such staining when using the Polyquad-based system. These
      results were significantly different (p < 0.001). Significant symptoms were not
      correlated with the degree of staining, with no differences in lens comfort or
      overall preference being reported between the regimens (p = NS). The only
      statistically significant difference in symptoms related to minor differences in
      stinging after lens insertion being reported, with the Polyquad-based system
      demonstrating less stinging (p < 0.008). CONCLUSIONS: Practitioners who fit
      silicone-hydrogel contact lenses on a daily wear basis should be wary of the
      potential for certain PHMB-containing multipurpose care systems to invoke corneal
      staining. Switching to non-PHMB based regimens will eliminate this complication
      in most instances.

PMID- 12512684
TI  - Assessments of corneal endothelial cell density in growing children and its
      relationship to horizontal corneal diameter.
AB  - BACKGROUND: Few studies have been published of corneal endothelial cell density
      (ECD) in children, especially in relation to the age and corneal size of the
      individuals. The possible effect of corneal enlargement on the endothelium was
      studied, and the results were objectively reviewed in relation to literature
      reports on corneal diameter and age. METHODS: ECD was assessed in 119 children
      aged 5 to 15 years after endothelial photography with a noncontact specular
      microscope (Topcon SP-1000 or SP-2000P), followed by manual digitization of cell
      overlays. The horizontal corneal diameter, as the visible iris diameter, was
      measured to 0.5-mm accuracy. RESULTS: The mean +/- SD value for ECD, calculated
      using all individual cell area values, was 3542 +/- 510 cells/mm2 (range, 2576 to
      5316), whereas it was 3246 +/- 416 cells/mm2 (range, 2404 to 4817) if the mean
      cell area value from each image was used to calculate ECD. The mean horizontal
      corneal diameter was 11.48 +/- 0.58 mm (+/- SD). The corneal diameter was not
      obviously age-related for this group, but there were clear trends for younger
      children to have higher ECD values than older children (p2, depending on the
      method for calculating ECD. CONCLUSIONS: ECD values were found to be
      significantly correlated to corneal diameter in children aged 5 to 15 years, and
      this factor should be considered in comparative studies.

PMID- 12512685
TI  - Stereoacuity at distance and near.
AB  - PURPOSE: Because previous studies have reported conflicting evidence, we examined
      a possible difference in stereoacuity between distance and near, in particular
      using a random-dot display. We compared distance and near stereoacuities using
      identical presentation formats at the two distances. METHODS: Twelve young adults
      with low, stable refractive errors and apparently normal binocular vision
      participated. Stereoacuity was determined with a Mentor B-VAT II using Random Dot
      E (BVRDE) and Contour Circles (BVC) stereograms presented on a standard monitor
      (25 x 19.3 cm) at 518 cm (distance-habitual) and a small monitor (2.0 x 1.4 cm)
      at 40 cm (near-habitual). To examine whether accommodation-convergence influenced
      stereoacuity, testing at 40 cm was repeated with the addition of +2.50 DS lenses
      and base-in prisms (near-compensated) that created the same accommodation and
      convergence demands as for distance-habitual viewing. RESULTS: The two
      stereotests produced similar findings. Stereoacuity was not significantly
      different for distance-habitual and near-habitual viewing of the BVRDE (p = 0.43)
      and BVC (p = 0.79) stereotests. Near-compensated stereoacuity was worse than near
      habitual (BVRDE, p = 0.005; BVC, p = 0.004) and distance-habitual (BVRDE, p =
      0.05; BVC, p = 0.003) for both stereotests. Because near stereoacuity with yoked
      prisms (control condition) was the same as without prism (near-habitual), prism
      induced optical distortions cannot account for the difference. CONCLUSIONS:
      Stereoacuity was not different at distance and near under normal viewing
      conditions. The conflict between subject knowledge of target proximity and the
      optically-induced relaxation of accommodation and convergence, or an inaccurate
      accommodative-convergence response, might have caused poor near-compensated
      stereoacuity.

PMID- 12512686
TI  - Evaluating relative accommodations in general binocular dysfunctions.
AB  - PURPOSE: To examine the relationship between relative accommodation and general
      binocular disorders and to establish their importance in the diagnosis of these
      anomalies. METHODS: We analyzed data of negative relative accommodation (NRA) and
      positive relative accommodation (PRA) in 69 patients with nonstrabismic binocular
      anomalies. RESULTS: Statistical analysis showed that low values of NRA and PRA
      were not associated with any particular disorder. High values of PRA (> or = 3.50
      D) were related to the disorders associated with accommodative excess, whereas
      high values of NRA (> or = 2.50 D) were not related to accommodative excess.
      Statistical differences suggested that a high value of PRA could distinguish
      between anomalies. Sensitivity analysis revealed that high PRA was the most
      sensitive sign in patients with convergence insufficiency combined with
      accommodative excess (0.89) and one of the most sensitive signs for subjects with
      accommodative excess (0.72) and for those with convergence excess combined with
      accommodative excess (0.70). CONCLUSIONS: Anomalous results of NRA were not
      clearly associated with any dysfunction. High values of PRA were related to
      disorders associated with accommodative excess, so the sign of a high value of
      PRA should be considered as one of the diagnostic signs of these anomalies.

PMID- 12512687
TI  - The dependency of logMAR visual acuity measurements on chart design and scoring
      rule.
AB  - BACKGROUND: Visual acuity, increasingly measured using a logarithm of the minimum
      angle of resolution (logMAR) chart, is the "gold standard" by which the outcomes
      of the vast majority of clinical trials or interventions are judged. To allow
      comparison of results across studies, it is important that different charts
      provide equivalent results. METHODS: In a first experiment, we compared corrected
      visual acuity measurements from four different logMAR charts (Bailey-Lovie,
      ETDRS, Regan, and Waterloo). In a second experiment we compared unaided visual
      acuity scored using a psychometric function with the more clinical by-letter
      scoring. RESULTS: Experiment 1 showed significantly better visual acuity using
      the Regan chart compared with the other three charts, and further investigation
      suggested that this could be due to the font type used. Repeatability data from
      experiment 2 indicated that no extra repeatability was gained when using
      psychometric methods compared with the far simpler and quicker by-letter scoring.
      CONCLUSIONS: When comparing findings between studies, the type of chart and the
      scoring method used may have a significant effect on the results obtained and
      should therefore be taken into consideration. Also, the additional time and
      effort demanded for determining a psychometric function for single readings of
      the Regan visual acuity chart is not rewarded with improved repeatability.

PMID- 12512688
TI  - Nitric oxide as a unique signaling molecule in the vascular system: a historical
      overview.
AB  - In retrospect, basic research in the fields of NO and cyclic GMP during the past
      two decades appears to have followed a logical course beginning with the findings
      that NO and cyclic GMP are vascular smooth muscle relaxants, that nitroglycerin
      relaxes smooth muscle by metabolism to NO, progressing to the discovery that
      mammalian cells synthesize NO, and finally the revelation that NO is a
      neurotransmitter mediating vasodilation in specialized vascular beds. A great
      deal of basic and clinical research on the physiological and pathophysiological
      roles of NO in cardiovascular function has been conducted since the discovery
      that EDRF is NO. The new knowledge on NO should enable investigators in this
      field to develop novel and more effective therapeutic strategies for the
      prevention, diagnosis and treatment of numerous cardiovascular disorders. Since
      NO elicits a protective and beneficial action in many disease states, novel NO
      donor drugs for clinical use should prove to be very effective drugs for the
      treatment of essential hypertension, stroke, coronary artery disease, vascular
      complications of diabetes, impotency and other disorders involving the vascular
      system.

PMID- 12512689
TI  - Mechanisms of superoxide production in human blood vessels: relationship to
      endothelial dysfunction, clinical and genetic risk factors.
AB  - Common vascular disease states including diabetes, hypertension and
      atherosclerosis are associated with endothelial dysfunction, characterised by
      reduced bioactivity of nitric oxide (NO). Loss of the vasculoprotective effects
      of NO contributes to disease progression, but the mechanisms underlying
      endothelial dysfunction remain unclear. Increased superoxide production in animal
      models of vascular disease contributes to reduced NO bioavailability, endothelial
      dysfunction and oxidative stress. In human blood vessels, the NAD(P)H oxidase
      system is the principal source of superoxide, and is functionally related to
      clinical risk factors and systemic endothelial dysfunction. Furthermore, the
      C242T polymorphism in the NAD(P)H oxidase p22phox subunit is associated with
      significantly reduced superoxide production in patients carrying the 242T allele,
      suggesting a role for genetic variation in modulating vascular superoxide
      production. In vessels from patients with diabetes mellitus, endothelial
      dysfunction, NAD(P)H oxidase activity and protein subunits are significantly
      increased compared with matched non-diabetic vessels. Furthermore, the vascular
      endothelium in diabetic vessels is a net source of superoxide rather than NO
      production, due to dysfunction of endothelial NO synthase (eNOS). This deficit is
      dependent on the eNOS cofactor, tetrahydrobiopterin, and is in part mediated by
      protein kinase C signalling. These studies suggest an important role for both the
      NAD(P)H oxidases and endothelial NOS in the increased vascular superoxide
      production and endothelial dysfunction in human vascular disease states.

PMID- 12512690
TI  - The eicosanoid factor: a determinant of individuality of nephron segments.
AB  - BACKGROUND: Nephron function is segmented, each segment has characteristic
      transport mechanisms and individual eicosanoid profiles. The transport function
      of the medullary thick ascending limb of Henle's loop (mTAL) establishes the
      osmolar gradient upon which extra cellular fluid volume (ECFV) conservation
      depends. The overriding importance of the mTAL to regulation of ECFV is evident
      in the diuretic-natriuretic potency of furosemide-like agents which target the
      mTAL. RESULTS: The mTAL has been shown to be heavily invested with cytochrome
      P450 monooxygenases (CYP), chiefly omega/omega-1 hydroxylase activity, that
      generate 19- and 20-hydroxyeicosatetraenoic acid (HETEs). However, displacement
      of omega hydroxylase by an inducible cyclooxygenase mechanism (COX-2) can be
      effected by several interventions: long-term infusion of angiotensin II (ANG II),
      adrenalectomy and elevated extracellular Ca2+ concentrations. This switching
      mechanism (CYP > COX-2) has been shown to be dependent on activation of tumor
      necrosis factor alpha (TNFalpha) by ANG II. It represents a long-term adaptive
      mechanism of the mTAL with production of PGE2 whereas in the short-term, ANG 11
      increases 20-HETE synthesis by the mTAL. The effect of Ca2+ on mTAL eicosanoid
      related mechanisms provides an explanation for the natriuretic response to
      hypercalcemia and diminished ability to concentrate urine. CONCLUSION: The
      expression of COX-2 in the TAL has been linked to activation of the renin
      angiotensin system, glucocorticoid deficiency and hypercalcemia, all of which
      operate through a mechanism in which production of TNFalpha by the TAL is
      pivotal.

PMID- 12512691
TI  - Angiotensin-(1-7): an active member of the renin-angiotensin system.
AB  - Angiotensin-(1-7) [Ang-(1-7)] is an active member of renin-angiotensin system
      (RAS). It counterbalances vasoconstriction, mitogenic, arrhythmogenic and
      prothrombotic actions of Ang II. Inducing natiuresis and diuresis opposes also
      the water and sodium retention produced by Ang II. Till now the specific receptor
      side for Ang-(1-7) has been not cloned, but the current data strongly suggest
      that an interaction (cross-talk) between angiotensin receptors may play a role in
      the effects of Ang-(1-7).

PMID- 12512692
TI  - A novel, potent and selective inhibitor of the activity of inducible nitric oxide
      synthase (GW274150) reduces the organ injury in hemorrhagic shock.
AB  - An enhanced formation of nitric oxide (NO) by the inducible NO synthase (iNOS)
      may contribute to the pathophysiology of hemorrhagic shock. This study
      investigates the effect of a novel, potent and selective inhibitor of iNOS
      activity (GW274150) on the circulatory failure and the organ injury and
      dysfunction associated with hemorrhagic shock in the anesthetised rat. Hemorrhage
      (sufficient to lower mean arterial blood pressure to 45 mmHg for 90 min) and
      subsequent resuscitation with shed blood resulted (within 4 h after
      resuscitation) in a delayed fall in blood pressure, renal and liver injury and
      dysfunction as well as the pancreatic injury. Pre-treatment of rats with GW274150
      (5 mg/kg at 30 min prior to the onset of hemorrhage) attenuated the renal
      dysfunction as well as the liver and pancreatic injury caused by hemorrhage and
      resuscitation. Interestingly, GW274150 did not reduce the delayed fall in blood
      pressure associated with hemorrhagic shock. We propose that an enhanced formation
      of NO from iNOS contributes to the organ injury and dysfunction in hemorrhagic
      shock, and that highly selective inhibitors of iNOS activity, such as GW274150,
      may represent a novel therapeutic approach for the therapy of hemorrhagic shock.

PMID- 12512693
TI  - Flavonoids and nitric oxide synthase.
AB  - Induction of NOS-2 in macrophages and smooth muscles within vascular wall with
      concomittant suppression of endothelial NOS-3 activity is considered to be a
      hallmark of vascular inflammation that triggers atherogenesis. Accordingly, drugs
      designed to reverse these changes should not only support vaning function of NOS
      3 but also suppress proinflammatory NO production by NOS-2. It means that using
      selective inhibitors of induction of NOS-2 (they spare ex definitione
      constitutive activity of NOS-3) is a more rational approach than using
      "selective" inhibitors of activity of previously induced NOS-2. First of all,
      those drugs are never sufficiently selective. In our work we tried to identify
      inhibitors of NOS-2 induction within the group of flavonoids, known stimulators
      of NOS-3 with putative antiatherogenic effects. Representatives of four main
      groups of flavonoids: flavonols (kaempferol, quercetin, rutin), flavones
      (apigenin, primuletin), flavanols (catechine) and flavanones (hesperetin,
      hesperidin, naringenin) were tried on NOS-2 induction and activity in the in
      vitro model of LPS-treated macrophages (cell line J774.2). While none of these
      compounds inhibited activity of NOS-2, all with unexpectedly scattered potencies
      inhibited induction of NOS-2 protein in LPS-treated J774.2 cells, as evidenced by
      Western blotting technique. Subsequently, RT-PCR and Northern blotting methods
      revealed that so far the most potent compounds, kaempferol and apigenin, at
      micromolar concentrations did inhibit NOS-2 induction at the level of NOS-2 gene
      transcription. We conclude that some of flavonoids are potent inhibitors of NOS-2
      induction. At the same time they may increase endothelial NOS-3 activity. Could
      these flavonoids become natural parents of future drugs, which will be used for
      reversal of inflammatory component of atherothrombosis?

PMID- 12512694
TI  - Cerivastatin potentiates nitric oxide release and enos expression through
      inhibition of isoprenoids synthesis.
AB  - Endothelium dysfunction, which is often defined as a decrease in NO
      bioavailability, is one of the earliest manifestations of endothelium-impaired
      function disorders, including atherosclerosis. Although improvement in NO
      bioavailability has been attributed to the lowering of serum cholesterol levels,
      recent studies suggest that HMG-CoA reductase inhibitors, statins, may have
      direct effects on NO bioavailability by little known mechanisms that are
      independent of serum cholesterol levels. The long-term effect of cerivastatin on
      NO release from endothelial cells was determined by using highly sensitive
      electrochemical microsensors and was correlated with endothelial NO synthase
      (eNOS) levels. To explore whether changes in isoprenoid synthesis affect NO
      bioavailability and eNOS expression, human endothelial cells were treated with
      cerivastatin, L-mevalonate (MVA; 1.5 mmol/L), geranylgeranylpyrophosphate (GGPP;
      1 mg/mL) and farnesylpyrophosphate (FPP; 1 mg/mL). Cerivastatin increased
      spontaneous (by 53% +/- 6) and an eNOS-stimulated NO release (by 41 +/- 6% for
      calcium ionophore and by 47 +/- 5% acetylcholine) as well as eNOS expression (by
      118 +/- 6%) in the same concentration-range. Cerivastatin-dependent increase in
      both NO release and eNOS expression was revealed after approximately 4 h of
      exposure reaching the maximum after approximately 10 h. Co-treatment with MVA or
      GGPP, but not FPP or LDL, reversed the effects of cerivastatin. These findings
      indicate that the long-term effect of cerivastatin resulting in enhanced NO
      bioavailabilty in endothelial cell is, at least in part, due to up-regulation of
      eNOS by blocking isoprenoids synthesis.

PMID- 12512695
TI  - Vascular effects of COX inhibition and AT1 receptor blockade in transgenic rats
      harboring mouse renin-2 gene.
AB  - Ang II-induced endothelial dysfunction is associated with perivascular
      inflammation and increased superoxide production in the vascular wall. The
      present study examined the role of cyclo-oxygenase (COX)-synthetized eicosanoids
      in the pathogenesis of Ang II-induced endothelial dysfunction in transgenic rats
      harboring mouse renin-2 gene (mREN2 rats). Five-to-six-week-old, heterozygous
      mREN2 rats received the following drug regimens for 8 weeks: 1) vehicle, 2) cyclo
      oxygenase-2 (COX-2) inhibitor (MF-tricyclic [3-(3,4-difluorophenyl)-4-(4
      (methylsulfonyl) phenyl)-2(5H)-furanone], 14 mg/kg p.o.), 3) COX-1/COX-2
      inhibitor (sulindac, 14 mg/kg p.o.), 4) angiotensin II receptor antagonist
      (losartan 40 mg/kg p.o.). Normotensive Sprague Dawley (SD) rats served as
      controls. In vitro vascular responses of the descending aorta and renal artery
      were studied using organ bath system. mREN2 rats developed pronounced
      hypertension which was associated with impaired endothelium-dependent and
      endothelium-independent vascular relaxations in the aorta. In contrast, the
      relaxation responses of the renal arteries remained largely unchanged in mREN2
      rats. Urinary NO, excretion, a marker of total body NO generation, was also
      decreased in mREN2 rats. Neither non-selective COX inhibitor sulindac nor COX-2
      selective MF-tricyclic were capable of preventing Ang II-induced hypertension or
      endothelial dysfunction in mREN2 rats, whereas ATi receptor antagonist losartan
      completely normalized blood pressure, vascular relaxation responses as well as
      urinary NOx excretion. Our findings indicate that NO synthesis and/or
      bioavailability as well as the sensitivity of arterial smooth muscle cells to NO
      are decreased in mREN2 rats. The present study also demonstrated that COX does
      not play a central role in the pathogenesis of Ang II-induced endothelial
      dysfunction in mREN2 rats.

PMID- 12512696
TI  - No-dependent vasodilation induced by nebivolol in coronary circulation is not
      mediated by beta-adrenoceptors or by 5 HT1A-receptors.
AB  - Nebivolol is a unique beta1-adrenoceptor antagonist which possesses peripheral
      vasodilator properties dependent on endothelial NO. Nebivolol-induced release of
      NO was attributed to its L stereoisomer and to its ability to stimulate
      endothelial beta2, beta3 adrenoceptors or 5-HT1A receptors. Here, in the isolated
      guinea pig heart we analysed coronary vasodilator potency of L- and D-nebivolol
      and a possible role of beta2, beta3 adrenoceptors and 5-HT1A receptors in
      nebivolol-induced vasodilation. Surprisingly, we found that not only L-nebivolol
      (3-30 x 10(-6) M) but also D-nebivolol (3-30 x 10(-6) M) induced coronary
      vasodilation, and both responses were inhibited by L-NAME (10(-4) M). In contrast
      with the stereoisomers of nebivolol, atenolol at the equimolar concentrations did
      induce slight vasoconstriction. The nonselective beta1/beta2-adrenoceptor
      antagonist--nadolol (10(-5) M), the selective beta3-adrenoceptor antagonist--L
      748337 (10(-6) M) and the 5 HT1A receptor antagonist--NAN 190 (5 x 10(-6) M),
      none of them inhibited coronary vasodilation induced by D- and L-nebivolol. In
      summary, in the isolated guinea pig heart both D- and L-nebivolol act as coronary
      vasodilators. Coronary vasodilation induced by stereoisomers of nebivolol is
      mediated by endothelium-derived NO and does not depend on beta2, beta3
      adrenoceptors or 5 HT1A receptors.

PMID- 12512697
TI  - Synthesis and thrombolytic activity of new thienopyrimidinone derivatives.
AB  - It has been observed that ticlopidine and clopidogrel show, apart from their
      delayed antiplatelet properties, an immediate and transient thrombolytic action
      related to the ability of these thienopyridines to stimulate the secretory
      function of vascular endothelium. With the objective to construct new molecules
      with identical thrombolytic potency but at a higher level, we carried out
      different structural modifications in the thienopyridine chemical molecule to
      conclude that the presence of a second N atom in the pyridine cycle (yielding
      pyrimidine moiety) and the presence of an additional cycle fused to the thienyl
      ring would lead to enhanced thrombolytic effects. Here we report the six-step
      synthesis of a series of new benzothienopyrimidinone derivatives characterized by
      this searched for potent thrombolytic activity. The pharmacological assay used
      anaesthetised Wistar rats with extracorporal circulation in which arterial blood
      superfused thrombi adhering to a strip of collagen. Weight of thrombi was
      continuously monitored. Six compounds of the series were much more potent
      thrombolytic agents than their thienopyridine references: the effective
      thrombolytic dose that produced 30% of maximum thrombolysis (ED30) was at a range
      of 8 to 170 microg kg(-1) as compared with ED30 values of 16000 to 20000 microg
      kg(-1) for clopidogrel and ticlopidine respectively. Especially with the most
      active compound, this difference in the threshold thrombolytic dose, giving an
      intensity of action higher by three orders of magnitude, was accompanied by a
      lengthening of the response. Apart from that these compounds have shown to be
      synthetic thrombolytics, they certainly deserve further studying.

PMID- 12512698
TI  - Misoprostol as agonist of IP2 receptor.
AB  - Fourteen patients with peripheral vascular disease received 200 microg of
      misoprostol 3 times a day during one month. The therapy with misoprostol caused
      clinical and biochemical improvement in all 14 patients. An elongation of pain
      free and maximum walking distance, shortening of pain duration and increase in
      arterial blood flow in both calves were observed. At the same time an activation
      of the fibrinolytic system, rise in the platelet aggregate ratio and increase in
      cAMP levels were noticed. It is suggested that misoprostol in human being caused
      rather activation of IP2 receptor.

PMID- 12512699
TI  - Interleukin 1beta induces functional prostaglandin E synthase in cultured human
      umbilical vein endothelial cells.
AB  - Prostaglandin endoperoxide H2 (PGH2) is generated from arachidonic acid by either
      constitutive (COX-1) or inducible (COX-2) cyclooxygenases. In arterial wall PGH2
      is converted by PGI2 synthase (PGI-S) to prostacyclin (PGI2), and in platelets by
      thromboxane synthase (TX-S) to thromboxane (TXA2). Other prostanoids as PGD2,
      PGF2alpha, or PGE2 were believed to arise non-enzymatically from PGH2. Only
      recently, human prostaglandin E synthase (PGE-S) has been identified and cloned
      as a membrane bound, microsomal, glutathione-dependent inducible enzyme. Here we
      demonstrated that interleukin 1beta (IL-1beta) is an inducer of COX-2 and PGE-S
      in human umbilical vein endothelial cells (HUVEC). Functional expression of PGE-S
      was measured at the level of specific mRNA by semi-quantitative RT-PCR, PGE-S
      protein was detected by Western blot in HUVEC, while PGE2 was measured by
      immunoassay in the supernatant. Actinomycin D, a classical transcription
      inhibitor, was used to prove that indeed IL-1beta induced the functional PGE-S
      enzyme. PGE2 generation in HUVEC was inhibited by indomethacin, acetaminophen and
      dexamethasone. In conclusion, we found that in cultured endothelial cells IL
      1beta induced as evidenced by the appearance of its transcript and its functional
      enzyme. The induction of endothelial PGE-S and COX-2 appeared to be and their
      transcripts were induced as fast as one might expect from immediate early genes.
      It means that IL-1beta-triggered-PGE2 biosynthesis in endothelial cells is
      probably regulated by induction of both COX-2 and PGE-S. This is way we
      hypothesise the existence of at least two distinct pools of COX-2: the first
      selectively coupled to PGE-S and the second one that is coupled to PGI-S yielding
      the main endothelial product--PGI2.

PMID- 12512700
TI  - Endothelial secretogogues and deformability of erythrocytes.
AB  - Many diseases of the heart and circulatory system have been linked with both
      dysfunction of vascular endothelium and insufficient deformability of
      erythrocytes. Using shear stress laser diffractometry we investigated whether
      deformability of erythrocytes would be regulated endogenously by generation of
      two endothelial secretogogues: prostacyclin and nitric oxide. Experiments were
      performed in rats ex vivo and with whole blood or isolated erythrocytes in vitro.
      Iloprost--a stable analogue of prostacyclin (10 microg/kg i.v.) and SIN-1 (NO
      donor) at a dose of 2 mg/kg/min i.v induced a significant improvement of
      deformability of erythrocytes ex vivo. Improvements of deformability by these two
      compounds were also evident in vitro when they were applied at a range of
      concentrations of 1 microM and 3 microM, respectively. Cyclooxygenase
      (indomethacin 20 mg.kg i.v.) and nitric oxide synthase (L-NAME 10 mg/kg i.v.)
      inhibitors while worsening deformability ex vivo, they did not affect (3 mM and
      10 microM, respectively) rheological functions of erythrocytes in vitro.
      Aggravating effects of these inhibitors on erythrocyte deformability ex vivo were
      reversed by prostacyclin and nitric oxide supplemented exogenously. Aspirin at a
      low (1 mg/kg i.v.) and high dose (50 mg/kg i.v.), contrary to indomethacin and L
      NAME, aggravated erythrocyte deformability either ex vivo or in vitro. It is
      concluded that autocrine function of vascular endothelium plays an important role
      in regulation of rheology of red blood cells in flowing blood. The mechanism of
      this phenomenon is unclear but some possible explanations are discussed. In
      addition, in our experiments aspirin revealed unique erythrocyte damaging
      properties, possibly independent of inhibition of cyclooxygenase, but related to
      a direct protein acetylation.

PMID- 12512701
TI  - The role of G protein beta subunits in the release of ATP from human
      erythrocytes.
AB  - Previously, we demonstrated that adenosine triphosphate (ATP) is released from
      human erythrocytes in response to mechanical deformation and that this release
      requires activation of a signal-transduction pathway involving adenylyl cyclase
      and the heterotrimeric G protein, Gs. Here we investigate the role of
      heterotrimeric G proteins of the Gi subtype in the release of ATP from human
      erythrocytes. In addition, we determined the profile of heterotrimeric G protein
      beta subunits present in these erythrocyte membranes. The activity of Gi was
      stimulated by incubation of erythrocytes (20% hematocrit) with mastoparin (10
      microM). ATP release was measured using the luciferin/luciferase assay.
      Heterotrimeric G protein beta subunits present in erythrocyte membranes were
      resolved using gel electrophoresis and subunit specific antibodies. Incubation of
      human erythrocytes with mastoparan (an activator of Gi/o) resulted in a 4.1 +/-
      0.6-fold increase in ATP present in the medium (P<0.01). Human erythrocyte
      membranes stain positively for beta subunit types 1, 2, 3 and 4, all of which
      been reported to activate of some isoforms of adenylyl cyclase. Activation of the
      heterotrimeric G protein, Gi, results in ATP release from erythrocytes. This
      effect is may be related to the activity of beta subunits associated with this G
      protein in the human erythrocyte.

PMID- 12512702
TI  - In vitro studies of activation of phagocytic cells by bioactive peptides.
AB  - The effect of formyl chemotactic peptide (fCTP, fMet-Leu-Phe), beta-amyloid
      peptides (beta-AP, 1-42, 1-16 and 25-35), and bradykinin (BK) on functional
      activity of phagocytic cells has been investigated. Wheat germ agglutinin (WGA)
      was also used as a model membrane binding agent of polypeptide nature. Murine
      monocyte-macrophage cell line J774.2 and normal human blood polymorphonuclear
      (PMN) cells were used as target phagocytic cells. Their activity was
      quantitatively estimated by measuring phagocytosis of killed yeast cells. Beta-AP
      (1-41) maximally stimulated phagocytosis at 0.1 microg/ml, BK--at 1.0 microg/ml,
      and fCTP--at 2.0 microg/ml. Beta-AP (1-16) and beta-AP (25-35) were inactive in
      used test-systems. Phagocytosis-inducing activity of beta-AP (1-42) and BK
      reached maximal levels in 2 h and decreased after 4-6 h of incubation.
      Phagocytosis numbers were compared with the indicators of phagocytic cell
      activation, such as absorption of neutral red dye, glucose utilization,
      production of super-oxide anion (NBT-test) and nitrite accumulation (indicator of
      NO production). NBT-test, which may be related to the killing ability of
      phagocytic cells towards the ingested objects, was positive only in stimulated
      PMN leukocytes, while the nitrite accumulation was detected only in stimulated
      macrophages. Nitrite accumulation in macrophages was markedly induced by
      lipopolysaccharide and to a lower extent by 0.5 microg/ml beta-AP (1-42). In high
      dose (5.0 microg/ml) beta-AP suppressed nitrite accumulation in macrophages
      stimulated by lipopolysaccharide. Other studied peptides were inactive in
      inducing nitrite accumulation. Transforming growth factor type beta suppressed
      phagocytic activity of PMN cells activated by beta-AP or WGA. The anti
      inflammatory drugs (indomethacin and L-lysine aescinate) inhibited beta-AP (1-42)
      induced phagocytosis. The interrelations between the regulatory pathways of BK,
      beta-AP and fCTP are discussed.

PMID- 12512703
TI  - Paradoxical augmentation of bradykinin-induced vasodilatation by
      xanthine/xanthine oxidase-derived free radicals in isolated guinea pig heart.
AB  - Increased generation of reactive oxygen species contribute to endothelial
      dysfunction in atherosclerosis, hypertension and heart failure. Recently, it was
      suggested that bursts of superoxide anions may inactivate endothelial surface
      bound enzymes such as angiotensin converting enzyme (ACE). Here, we tested
      effects of xanthine/xanthine oxidase-derived superoxide anions on vascular
      responses and ACE activity in the isolated guinea pig heart. We analysed effects
      of intracoronary infusion of low concentration of xanthine oxidase (10 mU/ml) in
      the presence of xanthine (0,5 mM) (X/XO) on bradykinin, other endothelium
      dependent and independent vasodilators (acetylcholine, ADP, SNAP), as well as
      vasoconstrictor responses to angiotensin I and angiotensin II. Surprisingly, X/XO
      significantly augmented coronary response to bradykinin without an effect on
      responses to ADP, acetylcholine, SNAP, angiotensin I and angiotensin II. In
      contrast, inhibition of ACE by perindoprilate (100 nM) resulted in augmentation
      of bradykinin-induced vasodilatation as well as diminution of angiotensin I
      evoked vasoconstriction without an influence on other responses. In summary, in
      the isolated guinea pig heart, X/XO-derived free radicals selectively augmented
      coronary vasodilator response to bradykinin, which cannot be explained by X/XO
      induced derangement of ACE. The mechanism of this paradoxical phenomenon, which
      might represent a defensive response of the coronary circulation to oxidative
      stress requires further investigations.

PMID- 12512704
TI  - Saline containing phosphatidylcholine liposomes possess the ability to restore
      endothelial function damaged resulting from gamma-irradiation.
AB  - The protective action of passive saline filled ("empty") phosphatidylcholine
      liposomes (PCL) on endothelial function was examined in thoracic aortas obtained
      from gamma irradiated (6 Gy) Chinchilla rabbits, and then verified in experiments
      on non-anesthetized and anesthetized rats. Acetylcholine (ACh)-induced vascular
      relaxant responses in isolated vascular tissues rats were used as the test of
      endothelial integrity and its functional ability. It was shown that when added to
      the bath solution (100 microg/ml), PCL effectively restored endothelium-dependent
      ACh relaxations of isolated vascular rings damaged resulting from gamma
      irradiation but had no effect on endothelium-independent vascular responses to
      therapeutic nitric oxide (NO) donors. The liposomes were also without protective
      effect when injected to the rabbits intraperitoneally (30 mg/kg) 1 hour before
      irradiation. In contrast, PCL, being injected at the same dose 1 hour after
      radiation impact, promote normalization of both endothelium-dependent vascular
      responses to ACh and nitric oxide (NO) donors. PCL restored also the sensitivity
      of vascular tissues to authentic NO (aqueous NO solution) that was surprisingly
      increased after irradiation, and normalized relationship between ACh-stimulated
      NO release and relaxant response amplitudes in irradiated aortas. Experiments on
      non-anesthetized and anesthetized rats demonstrated that irradiation led to
      significant elevation in the level of arterial blood pressure without any changes
      in cardiac contractility. PCL administration (25 mg/kg, i.v.) effectively
      normalized an increased arterial blood pressure in irradiated animals. In
      conclusion, it appears that PCL due to its ability to normalize NO-dependent
      vascular tone control mechanisms might be worthwhile therapeutic approach in case
      of ionizing irradiation accident. These result support the concept that the
      depression of endothelium-dependent vascular responses after irradiation may be
      result of decreased NO bioavailability due to its conversion to less potent
      vasodilators during irradiation-induced oxidative attack.

PMID- 12512705
TI  - Ultrastructural alterations of endothelium covering advanced atherosclerotic
      plaque in human carotid artery visualised by scanning electron microscope.
AB  - Human atherosclerotic plaque morphology at its various stages was extensively
      documented using light microscopy. However, much less is known of the
      ultrastructure of the human atherosclerotic plaque, in particular of
      ultrastructure of endothelial cells in atherosclerosis. Here, we analysed
      alterations of endothelial cells covering advanced atherosclerotic plaque in
      carotid artery using scanning electron microscope. Examination was performed on
      specimens from atherosclerotic lesions of the interior carotid artery, collected
      from 8 patients who had undergone endarterectomy. We found wide spectrum of
      pathological alterations of the luminal surface of atherosclerotic plaque. In
      dominant part of the vessel, endothelial layer was preserved but displayed
      pronounced irregularities in endothelial architecture including appearance of
      cuboidal cells. Some endothelial cells were covered by numerous microvilli and/or
      contained "craters" disrupting continuous surface of the endothelium. Platelets
      and leukocytes adhering to endothelium were frequently observed. There were also
      areas of the vessel lumen with endothelial denudation, in which the
      subendothelial surface containing fibrin proteins and collagen fibrils were
      visible. Interestingly, signs of proliferation of endothelial cells tending to
      cover the partially denuded vessel were observed. In summary, in scanning
      electron microscope, preserved endothelial cells of advanced atherosclerotic
      plaque displayed pronounced pathology; whether any of these changes represent the
      ultrastructural correlate of endothelial dysfunction remains to be established.

PMID- 12512706
TI  - History by history statistical estimators in the BEAM code system.
AB  - A history by history method for estimating uncertainties has been implemented in
      the BEAMnrc and DOSXYznrc codes replacing the method of statistical batches. This
      method groups scored quantities (e.g., dose) by primary history. When phase-space
      sources are used, this method groups incident particles according to the primary
      histories that generated them. This necessitated adding markers (negative energy)
      to phase-space files to indicate the first particle generated by a new primary
      history. The new method greatly reduces the uncertainty in the uncertainty
      estimate. The new method eliminates one dimension (which kept the results for
      each batch) from all scoring arrays, resulting in memory requirement being
      decreased by a factor of 2. Correlations between particles in phase-space sources
      are taken into account. The only correlations with any significant impact on
      uncertainty are those introduced by particle recycling. Failure to account for
      these correlations can result in a significant underestimate of the uncertainty.
      The previous method of accounting for correlations due to recycling by placing
      all recycled particles in the same batch did work. Neither the new method nor the
      batch method take into account correlations between incident particles when a
      phase-space source is restarted so one must avoid restarts.

PMID- 12512707
TI  - A personal-computer-based method to obtain "star-shots" of mechanical and optical
      isocenters for gantry rotation of linear accelerators.
AB  - This work describes a method to obtain "star-shots" of the mechanical and optical
      isocenters of linear accelerators, similar to the star-shots of radiation
      isocenters normally obtained using films. In this method a digital camera is
      connected to a personal computer so that multiply exposed images can be taken at
      a fixed camera position. A mechanical pointer or a wire aligned along the optical
      axis can then be imaged by the camera. Multiple exposures at varying gantry
      angles are then superimposed on a digital image which can be analyzed by the
      computer to give a high-resolution star-shot. The method provides a convenient
      way for a linear accelerator quality assurance procedure.

PMID- 12512708
TI  - Experimental determination of beam quality conversion factors k(Q) in clinical
      photon beams using ferrous sulphate (Fricke) dosimetry.
AB  - The implementation of protocols based on absorbed dose to water standards
      requires beam quality conversion factors, k(Q). Calculated values of k(Q) are
      available for ionization chambers used for reference dosimetry. Ideally, k(Q)
      should be experimentally determined at the same beam qualities as that of the
      user. In this work we measure k(Q) factors in clinical photon beams and compare
      them with calculated and measured values. Beam quality conversion factors are
      determined for clinical photon beams of nominal energies 4 MV, 6 MV, 15 MV, and
      25 MV, for commonly used cylindrical ionization chambers. Twelve chambers of
      eight different types are used. For three of them, no experimental data have
      previously been available. The experimental procedure is based on measurements
      with ionization chambers and Fricke dosimetry in the reference beam (60Co gamma
      radiation) and in clinical linear accelerator beams. The k(Q) values determined
      in this work generally agree within 0.5% with previously reported experimental
      values both when %dd(10)x and TPR2010 are used for beam quality specification.
      The agreement with calculated data is generally within 0.5%, except for the 15 MV
      beam. For this beam the measured values are usually between 0.5% and 1% lower
      than the data taken from the TG-51 protocol or the TRS-398 code of practice. For
      three NE2571 chambers and three NE2581 chambers, the maximum observed deviation
      of individual k(Q) values is 0.2% and 0.4%, respectively.

PMID- 12512709
TI  - Checking monitor unit calculations using coordinate transformations to calculate
      off-axis distances in the collimator frame of reference.
AB  - An important part of treatment-planning QA is to check Monitor Units (MUs)
      calculated by treatment-planning programs. This is generally straightforward,
      unless the central axis is blocked. One way to check MUs in this case is to
      select a reference point in the open portion of the field and use the off-axis
      distance (OAD), as well as other relevant data, to verify the dose. If wedges are
      employed in the treatment, the OAD must be specified in the collimator frame-of
      reference because one must know where the calculation point is with respect to
      the wedge to calculate the dose correctly. The purpose of this paper is to
      describe a method of calculating the OAD in the collimator frame-of-reference
      using the system of coordinate transformations described by Siddon

PMID- 12512710
TI  - A CdZnTe slot-scanned detector for digital mammography.
AB  - A new high-resolution detector has been developed for use in a slot-scanned
      digital mammography system. The detector is a hybrid device that consists of a
      CCD operating in time-delay integration mode that is bonded to a 150-microm-thick
      CdZnTe photoconductor array. The CCD was designed with a detector element pitch
      of 50 microm. Two devices were evaluated with differing crystalline quality.
      Incomplete charge collection was a source of reduction in DQE. This occurs in
      both devices due to characteristically low mobility-lifetime products for CdZnTe,
      with the greatest losses demonstrated by the multicrystalline sample. The
      mobility-lifetime products for the multicrystalline device were found to be 2.4 x
      10(-4) and 4.0 x 10(-7) cm2/V for electrons and holes, respectively. The device
      constructed with higher quality single crystal CdZnTe demonstrated mobility
      lifetime products of 1.0 x 10(-4) and 4.4 x 10(-6) cm2/V for electrons and holes.
      The MTF and DQE for the device were measured at several exposures and results
      were compared to predictions from a linear systems model of signal and noise
      propagation. The MTF at a spatial frequency of 10 mm(-1) exceeded 0.18 and 0.56
      along the scan and slot directions, respectively. Scanning motion and CCD design
      limited the resolution along the scan direction. For an x-ray beam from a
      tungsten target tube with 40 microm molybdenum filtration operated at 26 kV, the
      single crystal device demonstrated a DQE(0) of 0.70 +/- 0.02 at 7.1 x 10(-6) C/kg
      (27 mR) exposure to the detector, despite its relatively poor charge collection
      efficiency.

PMID- 12512711
TI  - Modification of prostate implants based on postimplant treatment margin
      assessment.
AB  - PURPOSE: To quantify the extent of additional source placement needed to perfect
      an implant after execution by standard techniques, assuming that uniform 5 mm
      treatment margins (TMs) is the criteria for perfection. MATERIALS AND METHODS:
      Ten consecutive, unselected patients treated with 1-125 brachytherapy were
      studied. Source placement is planned just inside or outside of the prostatic
      margin, to achieve a minimum 5 mm TM and a central dose of 150%-200% of the
      prescription dose. The preimplant prostate volumes ranged from 24 to 85 cc
      (median: 35 cc). The number of sources implanted ranged from 48 to 102 (median:
      63). Axial CT images were acquired within 2 h postoperatively for postimplant
      dosimetry. After completion of standard dosimetric calculations, the TMs were
      measured and tabulated at 45 degrees intervals around the prostate periphery at
      0.0, 1.0, 2.0, and 3.0 cm planes. Sources were then added to the periphery to
      bring the TMs to a minimum of 5 mm at each measured TM, resulting in a modified
      implant. All margin modifications were done manually, without the aid of
      automated software. RESULTS: Patients' original (unmodified) D90s ranged from
      111% to 154%, with a median of 116%. The original V100s ranged from 94% to 99%,
      with a median of 96%. No patient required placement of additional sources to meet
      a minimum D90 of 90% or a minimum V100 of 80%. In contrast, patients required
      from 7 to 17 additional sources (median: 11) to achieve minimum 5 mm TMs around
      the entire prostatic periphery. Additional sources equaled from 12% to 24% of the
      initial number of sources placed (median: 17%). By adding sufficient peripheral
      sources to bring the TMs to a minimum 5 mm, patients' average V100 increased from
      96% to 100%, and the average D90 increased from 124% to 160% of prescription
      dose. In the course of achieving a minimum 5 mm TM, the average treatment margin
      for all patients combined increased from 5.5 to 9.9 mm. The number of sources
      needed to bring the TMs to a minimum 5 mm was loosely correlated with the
      preimplant prostate volume and the change in prostate volume from implant-related
      swelling. Adding sufficient sources to achieve minimum 5 mm TMs increased the
      prostate volume receiving greater than 200% of the prescription dose (V200) from
      39% to 58%, and increased the average urethral point dose (2.00 cm inferior to
      the bladder) from 154% to 171% of the 144 Gy prescription isodose. CONCLUSIONS:
      Minimum 5 mm TMs are not uniformly achieved with current implant techniques. It
      seems that doing so, even in experienced hands, will require a reappraisal of our
      implant techniques, or the addition of intraoperative dosimetric analysis with
      the capacity to substantially modify the implant with extra sources.

PMID- 12512712
TI  - Particle in cell simulation of laser-accelerated proton beams for radiation
      therapy.
AB  - In this article we present the results of particle in cell (PIC) simulations of
      laser plasma interaction for proton acceleration for radiation therapy
      treatments. We show that under optimal interaction conditions protons can be
      accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The
      proton acceleration is due to the dragging Coulomb force arising from charge
      separation induced by the ponderomotive pressure (light pressure) of high
      intensity laser. The proton energy and phase space distribution functions
      obtained from the PIC simulations are used in the calculations of dose
      distributions using the GEANT Monte Carlo simulation code. Because of the broad
      energy and angular spectra of the protons, a compact particle selection and beam
      collimation system will be needed to generate small beams of polyenergetic
      protons for intensity modulated proton therapy.

PMID- 12512713
TI  - Photoacoustic tomography of biological tissues with high cross-section
      resolution: reconstruction and experiment.
AB  - A modified back-projection approach deduced from an exact reconstruction solution
      was applied to our photoacoustic tomography of the optical absorption in
      biological tissues. Pulses from a Ti:sapphire laser (4.7 ns FWHM at 789.2 nm)
      were employed to generate a distribution of photoacoustic sources in a sample.
      The sources were detected by a wide-band nonfocused ultrasonic transducer at
      different positions around the imaging cross section perpendicular to the axis of
      the laser irradiation. Reconstructed images of phantoms made from chicken breast
      tissue agreed well with the structures of the samples. The resolution in the
      imaging cross section was experimentally demonstrated to be better than 60 microm
      when a 10 MHz transducer (140% bandwidth at -60 dB) was employed, which was
      nearly diffraction limited by the detectable photoacoustic waves of the highest
      frequency.

PMID- 12512714
TI  - Using multiple-electrode impedance measurements to monitor cryosurgery.
AB  - We outfitted cryoprobes with electrodes and used them in conjunction with a
      multiple channel electrical impedance tomography (EIT) system to record data
      during freezing experiments in a shallow saline tank. We made measurements using
      electrodes mounted on the probes and the tank's periphery. Reconstructed images
      based on both sets of electrodes indicate a significant improvement in the
      appearance of the ice ball over using tank electrodes alone. The size of the ice
      balls was varied by deliberately altering the cooling rate. We found a positive
      correlation between the measured size of the ice ball and the sizes of isocontour
      lines in the reconstructed impedance maps. Similarly, the shape of the ice balls
      was altered by circulating the saline about the probe. Two-dimensional
      reconstructed impedance contours indicated a deformation in agreement with the
      shape of the ice ball during the experiments. These findings suggest that using
      multielectrode impedance sensing may constitute a means for monitoring
      cryosurgery.

PMID- 12512715
TI  - A technique of intensity-modulated radiosurgery (IMRS) for spinal tumors.
AB  - This study is to demonstrate the feasibility of spinal radiosurgery using an
      image-guided intensity-modulated radiosurgical (IMRS) procedure. A dedicated
      Novalis shaped beam surgery unit equipped with a built-in micro-multileaf
      collimator (mMLC) with a single 6 MV photon beam was used. Each patient was
      simulated in the supine position using an AcQsim CT simulator with infrared
      sensitive markers for localization. A variety of different treatment plans were
      developed, but the most common plan was the use of seven coplanar intensity
      modulated beams to minimize radiation to critical organs such as the spinal cord
      and kidneys. An automatic localization device based on infrared and video cameras
      was used to guide the initial patient setup. Two keV x-ray imaging systems were
      used to identify potential deviations from the planned isocenter. A total of 25
      patients with spinal tumors have been treated using this procedure with a single
      prescription dose ranging from 6 to 12 Gy. The final verification images
      indicated that the average isocenter deviation from the planned isocenter was
      within 2 mm. The phantom verification of isocenter doses indicated that the
      average deviation of measured isocenter doses from the planned isocenter doses
      for all patients treated with intensity-modulated beams was less than 2%. Film
      dose measurement in a phantom study demonstrated good agreement of above 50%
      isodose lines between the planned and measured results. Preliminary experience
      shows that precision delivery of high dose radiation could be administered to the
      planned target volume while the dose to the critical organs is kept within
      tolerable limits.

PMID- 12512716
TI  - Treatment planning for the layer-stacking irradiation system for three
      dimensional conformal heavy-ion radiotherapy.
AB  - We have upgraded a heavy-ion radiotherapy treatment-planning system to adapt for
      the layer-stacking irradiation method, which is to conform a variable spread-out
      Bragg peak to a target volume by means of dynamic control of the conventional
      beam-modifying devices. The biophysical model, the beam-setup logic, and the dose
      calculation algorithm implemented for the layer-stacking method are described and
      the expected clinical usability is discussed. The layer-stacking method was
      integrated in perfect accordance with the ongoing conventional treatments so that
      the established protocols, which are the clinically optimized dose fractionation
      schemes, will still be valid. On the other hand, a simulation study indicated a
      substantial improvement of dose distribution with the layer-stacking method
      though the significance may depend on the size, shape, and location of the tumor.
      The completed treatment system will provide an option for improved conformal
      radiotherapy without interfering with the conventional method and we expect a
      gradual expansion of the clinical cases applicable to the layer-stacking method.

PMID- 12512717
TI  - Performance evaluation of a pinhole SPECT system for myocardial perfusion imaging
      of mice.
AB  - The increasing use of transgenic mice as models of human physiology and disease
      has motivated the development of dedicated in vivo imaging systems for anatomic
      and functional characterization of mice as an adjunct to or a replacement for
      established ex vivo techniques. We have developed a pinhole single photon
      emission computed tomography (SPECT) system for high resolution imaging of mice
      with cardiovascular imaging as the primary application. In this work, we
      characterize the system performance through phantom studies. The spatial
      resolution and sensitivity were measured from images of a line source and point
      source, respectively, and were reported for a range of object-to-pinhole
      distances and pinhole diameters. Tomographic images of a uniform cylindrical
      phantom, Defrise phantom, and grid phantom were used to characterize the image
      uniformity and spatial linearity. The uniform phantom image did not contain any
      ring or reconstruction artifacts, but blurring in the axial direction was evident
      in the Defrise phantom images. The grid phantom images demonstrated excellent
      spatial linearity. A novel phantom modeling perfusion of the left ventricle of a
      mouse was designed and built with perfusion defects of varying sizes to evaluate
      the system performance for myocardial perfusion imaging of mice. The defect
      volumes were measured from the pinhole SPECT images and correlated to the actual
      defect volumes calculated according to geometric formulas. Linear regression
      analysis produced a correlation coefficient of r = 0.995 (p < 0.001),
      demonstrating the feasibility for measurement of perfusion defect size in mice
      using pinhole SPECT. We have performed phantom studies to characterize the
      spatial resolution, sensitivity, image uniformity, and spatial linearity of the
      pinhole SPECT system. Measurement of the perfusion defect size is a valuable
      phenotypic assessment and will be useful for hypothesis testing in murine models
      of cardiovascular disease.

PMID- 12512718
TI  - Energy response simulation of 4pi gamma ionization chambers using Monte Carlo
      technique.
AB  - The energy response of 4pi gamma re-entrant well-pressurized ionization chambers
      was calculated using the MCNP4B Monte Carlo computer code. Two different chambers
      were simulated-one filled with argon and the other with nitrogen gases at 2 MPa
      pressure. The MCNP4B results were in good agreement with the experimental
      measurements and the EGS4 Monte Carlo theoretical results. Energy response
      formulas for both chambers were obtained with respect to the 1.173 MeV gamma
      energy line of 60Co. Detailed energy response in the low energy region was
      facilitated by proper curve fitting of the simulation results. The MCNP4B code
      was also used to examine the effect of the axial displacement of the standard
      gamma source in the chamber well. The highest chamber response occurs when the
      source is located at the center position of the well and it decreases with
      increasing distance from the center. The effect of the source axial position
      displacement on the chamber energy response is noticeable at medium and high
      energy photon energies.

PMID- 12512719
TI  - Predicting film dose to aid in cassette placement for radiation therapy portal
      verification film images.
AB  - EC film has improved portal localization images with better contrast and improved
      distinction of bony structures and air-tissue interfaces. A cassette with slower
      speed screens was used with EC film to image the treatment portal during the
      entire course of treatment (verification) instead of taking separate films after
      treatment. Measurements of film density vs source to film distance (SFD) were
      made using 15 and 25 cm thick water phantoms with both 6 and 18 MV photons from I
      to 40 cm past the phantom. A characteristic (H & D) curve was measured in air to
      compare dose to film density. Results show the reduction in radiation between
      patient and cassette more closely follows an "inverse cube law" rather than an
      inverse square law. Formulas to calculate radiation exposure to the film, and the
      desired SFD were based on patient tumor dose, calculation of the exit dose, and
      the inverse cube relationship. A table of exposure techniques based on the SFD
      for a given tumor dose was evaluated and compared to conventional techniques.
      Although the film has a high contrast, there is enough latitude that excellent
      films can be achieved using a fixed SFD based simply on the tumor dose and beam
      energy. Patient diameter has a smaller effect. The benefits of imaging portal
      films during the entire treatment are more reliability in the accuracy of the
      portal image, ability to detect patient motion, and reduction in the time it
      takes to take portal images.

PMID- 12512720
TI  - A quality management program in intravascular brachytherapy.
AB  - While simple, intravascular brachytherapy (IVB) presents a considerable potential
      for harm to the patient. The medical physicist maintains the responsibility to
      minimize the likelihood of operational problems or dosimetric errors. The
      principals for safe operation remain the same as with any radiotherapy treatment:
      to deliver the correct dose, to the correct location, safety. To develop an
      effective and comprehensive quality management (QM) program for IVB, a physicist
      should utilize proven risk assessment techniques rather than simply thinking of
      things to check, and follow guidances such as ISO9001:2000. The proposed QM
      program includes the following: Procedures designed to assure the safety of the
      patient. Identification of the patient; tests of the integrity and patency for
      the delivery catheter, operation of the source train, and patency of the catheter
      in the treatment position; a check for recovery preparations; and verification of
      source recovery. Procedures to assure positional accuracy of the treatment:
      Verification of the positioning the catheter in the artery and of the sources in
      the catheter. Procedures to assure dosimetry accuracy: Acceptance testing of the
      device, including verification of the source strength and uniformity, and of the
      treatment duration tables; verification of the treatment prescription and
      duration for each patient; and control measures that minimize the likelihood of
      errors removing the source at the correct time.

PMID- 12512721
TI  - Maximum likelihood fitting of FROC curves under an initial-detection-and
      candidate-analysis model.
AB  - We have developed a model for FROC curve fitting that relates the observer's FROC
      performance not to the ROC performance that would be obtained if the observer's
      responses were scored on a per image basis, but rather to a hypothesized ROC
      performance that the observer would obtain in the task of classifying a set of
      "candidate detections" as positive or negative. We adopt the assumptions of the
      Bunch FROC model, namely that the observer's detections are all mutually
      independent, as well as assumptions qualitatively similar to, but different in
      nature from, those made by Chakraborty in his AFROC scoring methodology. Under
      the assumptions of our model, we show that the observer's FROC performance is a
      linearly scaled version of the candidate analysis ROC curve, where the scaling
      factors are just given by the FROC operating point coordinates for detecting
      initial candidates. Further, we show that the likelihood function of the model
      parameters given observational data takes on a simple form, and we develop a
      maximum likelihood method for fitting a FROC curve to this data. FROC and AFROC
      curves are produced for computer vision observer datasets and compared with the
      results of the AFROC scoring method. Although developed primarily with computer
      vision schemes in mind, we hope that the methodology presented here will prove
      worthy of further study in other applications as well.

PMID- 12512722
TI  - Artifacts associated with implementation of the Grangeat formula.
AB  - To compensate for image artifacts introduced in approximate cone-beam
      reconstruction, exact cone-beam reconstruction algorithms are being developed for
      medical x-ray CT. Although the exact cone-beam approach is theoretically error
      free, it is subject to image artifacts due to the discrete nature of numerical
      implementation. We report a study on image artifacts associated with the Grangeat
      algorithm as applied to a circular scanning locus. Three types of artifacts are
      found, which are thorn, wrinkle, and V-shaped artifacts. The thorn pattern is
      created by inappropriate extrapolation into the shadow zone in the radon domain.
      If the shadow zone is filled in with continuous data, the thorn artifacts along
      the boundary of the shadow zone can be removed. The wrinkle appearance arises if
      interpolated first derivatives of the radon data are not smooth between adjacent
      detector planes. In particular, the nearest-neighbor interpolation method should
      not be used. If the number of projections is not small, the bilinear
      interpolation method is effective to suppress the wrinkle artifacts. The V-shaped
      artifacts on the meridian plane come from the line integrations through the
      transition zones where derivative data change abruptly. Two remedies are to
      increase the sampling rate and suppress data noise.

PMID- 12512723
TI  - Optimum momentum transfer arguments for x-ray forward scatter imaging.
AB  - In our research program we have shown through modeling, related numerical
      calculations, and experimental measurements that there exists a potential use of
      scattered radiation for medical x-ray imaging. Each incident photon of wavelength
      lambda which scatters at a small angle theta with respect to its initial
      direction of travel has a change in momentum characterized by the photon momentum
      transfer argument x = lambda(-1) sin(theta/2). In this work, we show that in
      order to maximize the signal-to-noise ratio (SNR) obtained with scattered x rays,
      one must detect photons with specific x values. Using a photon counting detector
      to distinguish 2-cm-thick polymethyl methacrylate and nylon targets situated
      within a 15-cm-diam spherical water phantom with an 80 kV beam yields
      experimentally SNR/square root(K(air)c) = 12.8 +/- 0.2 (mJ/kg)(-1/2) when using
      the photons between x = 0.5 and 0.7 nm(-1). Here K(air)c is the air collision
      kerma and the average momentum transfer argument, x, is calculated by weighting x
      by the incident photon fluence distribution. The model predicts a value of
      SNR/square root(K(air)c) = 12.9 (mJ/kg)(-1/2). If we choose to form the signal
      with the range in x extended to be from 0.5 to 1.0 nm(-1) then, despite the
      detection of more scattered photons, experimentally SNR/square root(K(air)c)
      decreases by 38% to 7.9 +/- 0.3 (mJ/kg)(-1/2). The model predicts a value of 9.46
      (mJ/kg)(-1/2). Results for energy integrating detectors are in general similar to
      those for photon counters, but there exist cases where a significant decrease in
      SNR can occur. For example, for measurements in air with the two plastics at
      theta = 3 degrees the SNR for an energy integrator was found to be 52% that of a
      photon counter. Numerical calculations predict that the effects of spectral blur
      can be significant when a narrow angular range is used for detection. Preliminary
      numerical predictions for breast tissues suggest a potential use of x-ray scatter
      in the field of mammography.

PMID- 12512724
TI  - Optimization of a 90Sr/90Y radiation source train stepping for intravascular
      brachytherapy.
AB  - A steepest-descent gradient algorithm is developed to optimize the stepping of a
      90Sr/90Y radiation source train (RST) for intravascular brachytherapy (IVB). The
      objective function is to deliver a uniform dose in a coronary target vessel and
      minimize the dose in adjacent normal vessel tissue at the proximal and distal
      edges of the coronary target vessel. Based on the target length and number of
      dwell points (number of steps), the algorithm modulates the dwell times and
      corresponding dwell positions that optimize the weighted addition of staggered
      EGS4 Monte Carlo (MC) calculated dose distribution from a single RST. Stepping
      treatment plans are generated for target vessel lengths of 3.0, 3.3, and 3.8 cm.
      For both the unoptimized and optimized plans, the dose heterogeneity in the
      target vessel wall, and length of nontarget vessel receiving 3 Gy, is assessed to
      compare plans. Optimization results show a 14% dose uniformity within the target
      is achievable for all vessel lengths. Further, the dose in the adjacent normal
      tissue is lower in the optimized plans than the unoptimized plans. The work
      presented in this paper provides a model to address the finite length of RST in
      IVB treatments. While the results presented are specific to the 90Sr/90Y RST, the
      methods should apply to other finite length RSTs.

PMID- 12512725
TI  - Isotopic labeling with short-lived radionuclides represents the future for
      clinical PET imaging. For the proposition.

PMID- 12512727
TI  - Verification of multileaf collimator leaf positions using an electronic portal
      imaging device.
AB  - An automated method is presented for determining individual leaf positions of the
      Siemens dual focus multileaf collimator (MLC) using the Siemens BEAMVIEW(PLUS)
      electronic portal imaging device (EPID). Leaf positions are computed with an
      error of 0.6 mm at one standard deviation (sigma) using separate computations of
      pixel dimensions, image distortion, and radiation center. The pixel dimensions
      are calculated by superimposing the film image of a graticule with the
      corresponding EPID image. A spatial correction is used to compensate for the
      optical distortions of the EPID, reducing the mean distortion from 3.5 pixels
      (uncorrected) per localized x-ray marker to 2 pixels (1 mm) for a rigid rotation
      and 1 pixel for a third degree polynomial warp. A correction for a nonuniform
      dosimetric response across the field of view of the EPID images is not necessary
      due to the sharp intensity gradients across leaf edges. The radiation center,
      calculated from the average of the geometric centers of a square field at 0
      degrees and 180 degrees collimator angles, is independent of graticule placement
      error. Its measured location on the EPID image was stable to within 1 pixel based
      on 3 weeks of repeated extensions/retractions of the EPID. The MLC leaf positions
      determined from the EPID images agreed to within a pixel of the corresponding
      values measured using film and ionization chamber. Several edge detection
      algorithms were tested: contour, Sobel, Roberts, Prewitt, Laplace, morphological,
      and Canny. These agreed with each other to within < or = 1.2 pixels for the in
      air EPID images. Using a test pattern, individual MLC leaves were found to be
      typically within 1 mm of the corresponding record-and-verify values, with a
      maximum difference of 1.8 mm, and standard deviations of <0.3 mm in the daily
      reproducibility. This method presents a fast, automatic, and accurate alternative
      to using film or a light field for the verification and calibration of the MLC.

PMID- 12512728
TI  - Cone-beam CT with megavoltage beams and an amorphous silicon electronic portal
      imaging device: potential for verification of radiotherapy of lung cancer.
AB  - We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous
      silicon electronic portal imaging device (EPID) as a tool for patient position
      verification and tumor/organ motion studies in radiation treatment of lung
      tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The
      acquisition is automatic and requires 7 minutes for 100 projections; it can be
      synchronized with respiratory gating. From these images, volumetric
      reconstruction is accomplished with a filtered backprojection in the cone-beam
      geometry. Several important prereconstruction image corrections, such as detector
      sag, must be applied. Tests with a contrast phantom indicate that differences in
      electron density of 2% can be detected with 100 projections, 200 cGy total dose.
      The contrast-to-noise ratio improves as the number of projections is increased.
      With 50 projections (100 cGy), high contrast objects are visible, and as few as
      25 projections yield images with discernible features. We identify a technique of
      acquiring projection images with conformal beam apertures, shaped by a multileaf
      collimator, to reduce the dose to surrounding normal tissue. Tests of this
      technique on an anthropomorphic phantom demonstrate that a gross tumor volume in
      the lung can be accurately localized in three dimensions with scans using 88
      monitor units. As such, conformal megavoltage cone-beam CT can provide three
      dimensional imaging of lung tumors and may be used, for example, in verifying
      respiratory gated treatments.

PMID- 12512729
TI  - Contrast enhancement in dense breast images using the modulation transfer
      function.
AB  - This work proposes a method aimed at enhancing the contrast in dense breast
      images in mammography. It includes a new preprocessing technique, which uses
      information on the modulation transfer function (MTF) of the mammographic system
      in the whole radiation field. The method is applied to improve the efficiency of
      a computer-aided diagnosis (CAD) scheme. Seventy-five regions of interest (ROIs)
      from dense mammograms were acquired in two pieces of equipment (a CGR Senographe
      500t and a Philips Mammodiagnost) and were digitized in a Lumiscan 50 laser
      scanner. A computational procedure determines the effective focal spot size in
      each region of interest from the measured focal spot in the center for a given
      mammographic equipment. Using computational simulation the MTF is then calculated
      for each field region. A procedure that enlarges the high-frequency portion of
      this function is applied and a convolution between the resulting new function and
      the original image is performed. Both original and enhanced images were submitted
      to a processing procedure for detecting clustered microcalcifications in order to
      compare the performance for dense breast images. ROIs were divided into four
      groups, two for each piece of equipment-one with clustered microcalcifications
      and another without microcalcifications. Our results show that in about 10% of
      the enhanced images more signals were detected when compared to the results for
      the original dense breast images. This is important because the usual processing
      techniques used in CAD schemes present poor results when applied to dense breast
      images. Since the MTF method is a well-recognized tool in the evaluation of
      radiographic systems, this new technique could be used to associate quality
      assurance procedures with the processing schemes employed in CAD for mammography.

PMID- 12512730
TI  - Smoothing intensity-modulated treatment delivery under hardware constraints.
AB  - A method is developed to smooth intensity-modulated beam delivery while
      considering hardware constraints. The method uses matrix algebra to model MLC
      leaf motion and hardware constraints such as interleaf digitization,
      synchronization requirements, and intersegment field abutment to deliver
      intensity modulated beam sequences. It was implemented and demonstrated for
      simulated and clinical intensity modulated cases. The simulated cases included
      intensity distributions from 3 x 3 to 30 x 30 in dimension with 1,000 intensity
      levels. The clinical examples included four treatments sites: prostate, head and
      neck, lung, and esophagus cancers. In particular, we studied the relationships
      between the intensity levels, segment numbers and their influence on the dose
      volume histograms of the inversely optimized IMRT treatment plans. It was found
      that a significant reduction in the leaf segment numbers was achieved by applying
      the smoothing approach. The effects were found to be more significant for the
      unconstrained delivery than for the constrained delivery. The effects were also
      found to be more sensitive for the complex intensity distributions such as the
      head-and-neck cases than for the less complex ones such as the prostate cases.
      These results demonstrated the feasibility of maintaining inversely optimized
      treatment plans under acceptable tolerance levels while smoothing IMRT treatments
      with hardware constraints.

PMID- 12512731
TI  - The water equivalence of solid materials used for dosimetry with small proton
      beams.
AB  - Various solid materials are used instead of water for absolute dosimetry with
      small proton beams. This may result in a dose measurement different to that in
      water, even when the range of protons in the phantom material is considered
      correctly. This dose difference is caused by the diverse cross sections for
      inelastic nuclear scattering in water and in the phantom materials respectively.
      To estimate the magnitude of this effect, flux and dose measurements with a 177
      MeV proton pencil beam having a width of 0.6 cm (FWHM) were performed. The proton
      flux and the deposited dose in the beam path were determined behind water,
      lucite, polyethylene, teflon, and aluminum of diverse thicknesses. The number of
      out-scattered protons due to inelastic nuclear scattering was determined for
      water and the different materials. The ratios of the number of scattered protons
      in the materials relative to that in water were found to be 1.20 for lucite, 1.16
      for polyethylene, 1.22 for teflon, and 1.03 for aluminum. The difference between
      the deposited dose in water and in the phantom materials taken in the center of
      the proton pencil beam, was estimated from the flux measurements, always taking
      the different ranges of protons in the materials into account. The estimated dose
      difference relative to water in 15 cm water equivalent thickness was -2.3% for
      lucite, -1.7% for polyethylene, -2.5% for teflon, and -0.4% for aluminum. The
      dose deviation was verified by a measurement using an ionization chamber. It
      should be noted that the dose error is larger when the effective point of
      measurement in the material is deeper or when the energy is higher.

PMID- 12512732
TI  - A Monte Carlo based phase space model for quality assurance of intensity
      modulated radiotherapy incorporating leaf specific characteristics.
AB  - Dose calculations for intensity modulated radiation therapy (IMRT) require an
      accurate description of the radiation field defined by the multileaf collimator.
      A previously developed Monte Carlo phase space model has been modified to provide
      accurate dose verification for IMRT treatments on a Novalis linear accelerator.
      We have incorporated into the model the effects of the multileaf collimator
      geometry, including leaf transmission, interleaf leakage, the rounded leaf tips
      and the effects of leaf sequencing, as well as the beam divergence and energy
      variation across the field. The modified source model was benchmarked against
      standard depth dose and profile measurements, and the agreement between the
      calculation and measurement is within the AAPM Task Group No. 53 criteria for all
      benchmark fields used. Film dosimetry was used to evaluate the model for IMRT
      sequences and plans, and the ability of the model to account for leaf sequencing
      effects is also demonstrated.

PMID- 12512733
TI  - RFA:CA-03-002: network for translational research: optical imaging.

PMID- 12512734
TI  - Comment on "Mathematical morphology in computerized analysis of angiograms in age
      related macular degeneration".

PMID- 12512735
TI  - Comments on "On the role of intensity-modulated radiation therapy in radiation
      oncology".

PMID- 12512736
TI  - Update on aspirin in the treatment and prevention of cardiovascular disease.
AB  - Antiplatelet therapy, most notably aspirin, has been well documented to reduce
      risks of subsequent cardiovascular disease (CVD) in secondary prevention, acute
      myocardial infarction (MI), acute occlusive stroke, as well as in primary
      prevention. In secondary prevention, the most recent Antithrombotic Trialists'
      Collaboration reviewed 194 published randomized trials of antiplatelet therapy,
      mostly aspirin, involving more than 212 000 patients (ie, 135 000 using
      antiplatelet therapy or control and 77 000 using different antiplatelet
      regimens). In a very wide range of patients who have survived a prior occlusive
      vascular event-including MI, transient ischemic attacks, occlusive stroke,
      unstable and stable angina, percutaneous coronary interventions, and coronary
      artery bypass graft-aspirin prevents about 25% of serious vascular events. Among
      patients suffering acute Ml or acute occlusive stroke, aspirin begun promptly and
      continued long-term reduces risks of subsequent MI, stroke, and vascular death.
      In acute coronary syndromes, clopidogrel added to aspirin further reduces the
      risk of important vascular events, but not mortality, and causes more side
      effects, especially bleeding. For patients undergoing percutaneous coronary
      interventions, the addition of a short-term infusion of a glycoprotein IIb/IIIa
      receptor antagonist to aspirin prevents additional vascular events during the
      early in-hospital period but also increases the risk of major bleeding. Ongoing
      research is investigating other combinations of different antiplatelet drugs. In
      all these high-risk patients, there is a small excess of major bleeding among
      those assigned at random to aspirin, which is far outweighed by the magnitude of
      benefits on CVD. During an acute MI, after a loading dose of 160 mg to 325 mg
      aspirin, daily doses ranging from 75 to 150 mg daily are as effective as higher
      doses. For long-term treatment, the effects of doses < 75 mg daily are less
      certain. Although side effects are dose-related, especially in doses > 325 mg
      daily, no antiplatelet regimen is more effective than aspirin for long-term use.
      In primary prevention, 5 randomized trials have been published involving more
      than 60 000 apparently healthy men and women. Persons randomized to receive
      aspirin in these trials had significant reductions in risk of a first MI (32%)
      and important vascular events (15%). Since the numbers of strokes and vascular
      deaths were insufficient to distinguish between the benefits found in secondary
      prevention and no effect, use of aspirin in primary prevention should be weighed
      in light of the cardiovascular risk profile, the side effects of the drug, and
      its clear benefit in reducing risk of a first MI. Aspirin should be an adjunct,
      not an alternative, to managing other cardiovascular risk factors. Recently, the
      US Preventive Services Task Force and the American Heart Association recommended
      aspirin use for all men and women whose 10-year risks are > 6% and > or = 10%,
      respectively. In all these patient categories, including secondary prevention,
      acute MI and acute occlusive stroke, as well as primary prevention, increased and
      appropriate use of aspirin will prevent large numbers of premature deaths and
      MIs.

PMID- 12512737
TI  - Gastrointestinal safety of low-dose aspirin.
AB  - The cardioprotective benefits of aspirin support the use of low-dose regimens for
      primary and secondary prevention of cardiovascular disease. However, these
      cardioprotective benefits must often be balanced against the well-documented
      gastrointestinal (GI) effects of aspirin. Recent research suggests that the GI
      effects of aspirin may be dose-dependent; however, even low-dose aspirin can
      cause significant GI sequelae. Similarly, the use of nonaspirin nonsteroidal
      antiinflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 inhibitors, has
      also been shown to increase the risk of GI effects, and the concomitant use of
      aspirin and nonaspirin NSAIDs can significantly increase the risk of GI
      ulceration and bleeding. Therefore, clinicians should use the lowest effective
      dose of aspirin (ie, 75 to 150 mg/day) that affords cardiovascular benefits
      without increasing the risk of GI effects. Low-dose aspirin therapy can
      complicate the concurrent use of analgesics. When an analgesic is needed in
      addition to aspirin, concomitant use of aspirin and nonaspirin NSAIDs or COX-2
      inhibitors should be used with caution, or with concomitant gastroprotective
      agents, to minimize the risk of GI complications. In contrast, because
      acetaminophen does not cause GI irritation, it should therefore be considered
      when an analgesic is needed.

PMID- 12512738
TI  - Increased expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured
      endothelial cells exposed to serum from type 1 diabetic patients: no effects of
      high glucose concentrations.
AB  - Activation of the arterial endothelium may play an important role in the
      development of an atherosclerosis-prone vascular wall in diabetes. The induction
      of the adhesion molecules VCAM-1 and E-selectin on activated endothelial cells is
      crucial in monocyte recruitment during the atherogenic process. In the present
      study, we investigated whether sera from type 1 diabetic patients and non
      diabetic persons are capable of inducing expression of VCAM-1 and E-selectin in
      human endothelial cells cultured in vitro. First, it was found that the addition
      of serum from non-diabetics to the cultures resulted in expression of adhesion
      molecules above basal level and also increased the cellular response to the
      cytokine tumor necrosis factor-alpha (TNF-alpha), a strong inducer of both
      adhesion molecules. Moreover, it was found that, on average, sera from 17
      diabetic males induced a higher expression of VCAM-1 in the endothelial cells
      after 6 h of incubation than samples from 20 non-diabetic age-matched males (p <
      0.05). No difference between the diabetic and non-diabetic group was seen in the
      expression of E-selectin. Likewise, no differences were observed between the
      effects of the sera to induce TNF-alpha responsivity. A series of experiments
      showed that alterations in the glucose concentrations of the growth medium (5.5
      13.5 mmol/L) did not change the cellular content of either VCAM-1 or E-selectin
      before and after TNF-alpha treatment. In conclusion, it has been shown that sera
      from diabetic patients contain component(s), capable of inducing VCAM-1
      expression in endothelial cells independent of hyperglycemia. Augmented induction
      of endothelial VCAM-1 expression by circulating factor(s) may play a role in the
      development of atherosclerosis in diabetes.

PMID- 12512739
TI  - Effect of bupivacaine application on cholinesterase activities, total protein-
      and albumin concentration in serum and cerebrospinal fluid.
AB  - The rationale of this study was to determine whether Bupivacaine used for spinal
      anesthesia alters the specific secretory activity of nerve cells and/or the
      function of the blood/cerebrospinal fluid barrier. Four groups were assessed: (1)
      patients undergoing spinal anesthesia using Bupivacaine for lower limb surgery,
      (2) spinal Bupivacaine anesthesia without subsequent surgery, (3) local facet
      joint infiltration using Bupivacaine, and (4) general anesthesia for lower limb
      surgery without Bupivacaine application. Cholinesterase activities, total protein
      and albumin concentrations in serum as well as in cerebrospinal fluid were
      significantly decreased after surgical intervention under spinal Bupivacaine
      anesthesia but remained unchanged following spinal Bupivacaine application
      without surgery. No significant correlation was found between Bupivacaine dosage
      and parameter alteration. There was no influence of intrathecal Bupivacaine
      application on the albumin ratio cerebrospinal fluid/serum, nor was there any
      significant alteration of total protein- or albumin concentrations and
      butyrylcholinesterase activity in the serum as a result of local injection of
      Bupivacaine to facet joints. These serum parameters were reduced after surgery
      under general anesthesia. Alterations of serum- and cerebrospinal fluid
      parameters investigated after surgery are not related to Bupivacaine application
      but to effects linked to operative treatment, i.e. suppressed secretory cell
      activity or protein depletion owing to blood loss. We conclude that the secretory
      function of cholinesterase-releasing nerve cells is not affected by spinal
      application of Bupivacaine. The blood/cerebrospinal fluid barrier remains intact.

PMID- 12512740
TI  - Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in dialysis
      patients, renal transplant recipients and healthy controls.
AB  - It has been suggested that infection with Chlamydia pneumoniae plays a role in
      the development and maintenance of atherosclerosis based on differences in the
      prevalence of antibodies against Chlamydia pneumoniae in patients with and
      without atherosclerotic lesions and on the presence of bacteria in
      atherosclerotic lesions. It is well known that patients undergoing chronic
      dialysis treatment and renal transplant recipients have a considerably increased
      risk of cardiovascular disease. In this study it is hypothesized that patients
      with these conditions have a higher prevalence of Chlamydia pneumoniae DNA in the
      white cells of the peripheral blood. Blood samples from 196 dialysis patients,
      114 renal transplant recipients and 342 healthy controls were analysed with an in
      house nested polymerase chain reaction (nPCR) and tested for the presence of
      Chlamydia pneumoniae DNA. The prevalence of Chlamydia pneumoniae DNA was
      significantly higher in dialysis patients (16.3%) than in healthy controls (8.5%,
      p < 0.01), whereas no significant difference was found between the prevalence in
      renal transplant recipients (9.6%) and healthy controls. The prevalence was not
      related to gender or age in either group, and it was the same in diabetics and
      non-diabetics. Dialysis patients have a higher prevalence of Chlamydia pneumoniae
      DNA than healthy controls. The lower prevalence of Chlamydia pneumoniae DNA in
      renal transplant recipients than in dialysis patients may be due to selection of
      dialysis patients with few or no cardiovascular complications for renal
      transplantation. Our results are consistent with the hypothesis that Chlamydia
      pneumoniae is associated with the pathogenesis of atherosclerosis.

PMID- 12512741
TI  - Biological variation of retinoids in man.
AB  - This investigation was undertaken to assess biological variation, especially the
      within-subject variations of all-trans retinoic acid, 13-cis retinoic acid and
      retinol in human serum. Diurnal variation and variation over a week, a month and
      a year were studied in 11 males (aged 21-54 years) and 17 females (aged 22-63
      years), all subjectively healthy. We found no diurnal variation with the
      exception of all-trans retinoic acid, which had maximal concentrations at noon
      irrespective of food intake. Seasonal variations were marginal. Both all-trans
      and 13-cis retinoic acids had fairly high within-subject (13.1%, and 12.6%,
      respectively) and between-subject coefficients of variation (15.9% and 21.0%,
      respectively), while the within-subject CV of retinol was less (5.6%, with a
      between-subject CV of 21.1%). Thus, the indices of individuality were < 1 for all
      retinoids. The critical differences between two consecutive samples were < 40%
      for the retinoic acids and < 20% for retinol. Women had higher all-trans retinoic
      acid concentrations in serum (5.1 nmol/L vs. 4.5 nmol/L), lower 13-cis retinoic
      acid concentrations (4.5 nmol/L vs. 5.5 nmol/L) and lower retinol concentrations
      in serum (2.1 micromol/L vs. 2.5 micromol/L) than men. Thus, samples for retinoid
      determinations should be drawn in the morning and evaluated using separate gender
      reference intervals.

PMID- 12512742
TI  - Daily reduction in C-reactive protein values, symptoms, signs and temperature in
      group-A streptococcal pharyngitis treated with antibiotics.
AB  - C-reactive protein (CRP) value is usually elevated in patients with group A
      streptococcal (GAS) pharyngitis. The aim of this study was to describe the daily
      changes in CRP value after start of antibiotic treatment and to compare these
      changes with commonly used outcome measures in GAS pharyngitis. Eleven adult
      patients with sore throat and confirmed GAS infection were examined daily by
      specially trained medical students who registered symptoms and signs, performed a
      CRP test (NycoCard) and measured body temperature. At baseline, the mean CRP
      value was 100.3 mg/L (SD 80.9). The mean reduction after one day was 34.1% (SD
      15.3), after two days 60.1% (SD 14.1) and after three days 75.3% (SD 12.5).
      Corresponding reductions were found for sign and symptom scores and temperature,
      but the standard deviations for these measures were much larger. The CRP value
      was significantly associated with both the symptom score and the number of days
      after start of treatment (p < 0.01), but not with the sign score and body
      temperature, as shown by multiple regression analysis for repeated measurements.
      The CRP test seems to be a valid test for monitoring the clinical course in GAS
      pharyngitis.

PMID- 12512743
TI  - HFE mutations and hemochromatosis in Danish patients admitted for HFE genotyping.
AB  - Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to
      diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate
      the efficiency with which different hospitals and general practitioners select
      patients for HH genotype and to determine the distribution of HFE mutations in
      such patients. Nine hundred unrelated patients from Danish hospitals and general
      practitioners (group A) and 69 consecutive patients from a specialized liver unit
      (group B) were examined for HFE substitutions using multiplex real-time
      polymerase chain reaction. In group A we found 13.0% (0%) C282Y homozygotes, 5.8%
      (2.6%) H63D/C282Y compound heterozygotes and 1.9% (3.1%) S65C heterozygotes. The
      values for 420 Danish blood donors are shown in parentheses. The distribution of
      genotypes in group B was similar to that of the blood donors. Serum ferritin,
      transferrin iron saturation and pathological data were collected from 38 randomly
      selected C282Y homozygotes, 36 H63D/C282Y compound heterozygotes, 19 H63D
      heterozygotes, 17 S65C heterozygotes and 144 wild-types. All of the C282Y
      homozygotes and 28% of the compound heterozygotes were diagnosed as HH patients.
      There was no evidence of HH in the H63D homozygotes or S65C heterozygotes.
      Moreover, 7 wild-type patients, 2 C282Y heterozygote patients and one H63D
      heterozygote patient fulfilled the criteria for HH. The significant enrichment of
      HH among associated genotype samples submitted for HFE testing indicates that the
      clinical selection is generally adequate. However, the study showed substantial
      deviation in the selection efficiency among the various hospitals and general
      practitioners.

PMID- 12512744
TI  - Post-occlusive reactive hyperemia in single nutritive capillaries of the nail
      fold: methodological considerations.
AB  - Endothelial function at the arterial level has been extensively assessed by a non
      invasive method using flow-mediated dilatation (FMD) of the brachial artery.
      Early disturbances have been found in patient groups prone to later development
      of manifest macrovascular atherosclerosis. A possible non-invasive means of
      studying blood-flow regulation and function at the microcirculatory level is
      through videophotometric capillaroscopy. The most stable variable in such an
      investigation is the time-to-peak (TtP) flow after a brief arterial occlusion.
      The short-term reproducibility of such assessments is excellent but the
      coefficient of variation (CV) in long-term studies is reported to be in the order
      of slightly less than 20%. The aim of the present methodological study was to
      evaluate different sources of variations in such microcirculatory assessments in
      order to be able to propose design recommendations that minimize the number of
      patients and recordings needed to achieve sufficient statistical power in
      longitudinal studies. We used a symmetric design with 144 recordings of TtP after
      a one-minute arterial occlusion in healthy volunteers. We did six occlusions each
      time in the capillaries of two fingers on each occasion, and repeated the
      procedure three times with an interval of at least one week between each
      investigation. All recordings were analyzed off-line using a cross-correlation
      technique with the Capiflow system. Each analysis was performed at least three
      times, giving a total of slightly less than 500 assessments. In our material (n =
      10) TtP had a mean of 6.3 s (95% confidence interval 5.2-7.4). The correlation
      between repeated measurements in a single capillary during a single session was r
      > 0.91 (CV 6%). The between-finger CV was 8% (r = 0.84). The CV of measurements
      between different days was about 20% when single measurements were compared.
      However, the CV decreased to less than 13% when the mean of at least two time-to
      peak assessments on each occasion was used. In conclusion, the methodological
      error including day-to-day variation could be minimized using the mean of at
      least two repeated assessments of post-occlusive hyperemia at each time point in
      a longitudinal study. This finding should be taken into consideration in the
      design of future longitudinal studies.

PMID- 12512745
TI  - Influence of training habits on exercise-induced changes in plasma atrial and
      brain natriuretic peptide and urinary excretion of aquaporin-2 in healthy man.
AB  - The purpose of this study was to quantify the influence of training habits on the
      changes in plasma atrial natriuretic peptide (ANP), plasma brain natriuretic
      peptide (BNP) and urine aquaporin-2 (u-AQP2) during exercise by studying trained
      and untrained healthy subjects. Eleven trained subjects (7 males, 4 females) and
      10 untrained subjects (8 males, 2 females) performed a maximal aerobic exercise
      test. ANP and BNP were determined every 3 min and at maximum exercise by
      radioimmunoassay (RIA), and u-AQP2 was determined before and after the exercise
      test by RIA. The absolute increase in ANP during exercise was higher in the
      trained subjects (trained subjects: 5.6 pmol/L; untrained subjects: 2.4 pmol/L, p
      < 0.05) and was positively correlated to ANP at rest (p < 0.03). The maximum
      absolute increase in BNP during exercise was the same in the two groups (trained
      subjects: 0.5 pmol/L; untrained subjects: 0.6 pmol/L, NS) and tended to correlate
      positively with resting BNP in the trained subjects (p = 0.07). Exercise did not
      change u-AQP2 excretion in either trained subjects (rest: 372 ng/mmol creatinine;
      exercise: 314 ng/mmol creatinine, NS) or untrained subjects (rest: 263 ng/mmol
      creatinine; exercise: 338 ng/mmol creatinine, NS). The absolute increase in ANP
      during exercise was higher in trained subjects than in untrained subjects and was
      positively correlated to ANP at rest. This might reflect the normal
      cardiovascular adaptation to exercise. The increase in BNP during exercise was
      unrelated to training habits. Training habits did not affect the u-AQP2 excretion
      during exercise.

PMID- 12512746
TI  - Serum and plasma as alternative sample types in analysis of cardiac markers in
      the clinical routine.
AB  - There is an increasing demand for the results of cardiac markers (troponin I or
      T, creatine kinase MB mass and myoglobin) to be made available promptly after
      sample-taking. In order to shorten the turnaround time, the possibility of using
      EDTA- or heparin-plasma instead of serum was investigated. The study population
      comprised 391 patients with acute chest pain. Four different instruments and
      systems routinely used in Finland giving quantitative results were studied for
      the assays of creatine kinase isoenzyme MB mass, myoglobin, and troponin I or
      troponin T. In addition to serum samples, heparin-plasma seems to be useful for
      all three assays using the Access and Immulite systems, while EDTA-plasma seems
      to be useful for all three assays with the Access and Elecsys systems. For the
      AxSYM assays, serum samples seem to be the best alternative. In conclusion, it is
      possible to use a single EDTA- or heparin-plasma sample for Access, Elecsys and
      Immulite analysers, and thereby to shorten the turnaround time. In this way the
      quantitative analyses from plasma can be performed 30 min after taking the
      sample.

PMID- 12512747
TI  - Variability of the biological variation.
AB  - A great diversity among within-subject and between-subject biological variation
      data is shown from previously published works. Consequently, most of the proposed
      applications of biological variation to set metrological goals or requirements
      should be revisited.

PMID- 12512748
TI  - Live donor renal transplantation: extending the boundaries.

PMID- 12512749
TI  - Live donor renal transplantation in Australia 1964-1999: an evolving practice.
AB  - BACKGROUND: Australia has a low cadaver organ donor (CD) rate by international
      standards, leading to the increasing use of live donor (LD) renal grafts. AIMS:
      To review the Australian experience with LD transplants from 1964 to 1999.
      METHODS: Data were obtained from the Australian and New Zealand Dialysis and
      Transplant Registry. Survival was assessed by the Kaplan-Meier method. RESULTS: A
      total of 1584 LD and 10 252 CD transplants was performed between 1964 and 1999.
      While the CD rate dropped over the last decade, the LD rate increased,
      maintaining the overall transplantation rate. Only 3.6% of grafts before 1980
      were LD, increasing to 28.4% during 1995-1999. Patient and graft survival of LD
      grafts was superior to CD grafts. Most LD grafts were from live related donors
      (LRD), most commonly parents or siblings. The number of transplants from live
      unrelated donors (LURD) has risen (1980-1989, n = 6; 1990-1999, n = 143),
      primarily due to more spousal donation, with no difference in survival between
      LRD and LURD groups. Grafts from older donors (> 50 years of age) increased, with
      no graft survival difference between donors < 50 years and donors > 50 years. LD
      transplants performed prior to commencement of dialysis increased, with survival
      similar to grafts performed after dialysis. CONCLUSION: The pattern of renal
      transplantation in Australia has changed, with increasing numbers of LD
      transplants, growing use of unrelated and older donors, and more transplants
      before dialysis commences. Long-term patient and graft survival advantages have
      been maintained, supporting the growing use of live donors to expand the donor
      pool.

PMID- 12512750
TI  - Clinical features of Fabry's disease in Australian patients.
AB  - BACKGROUND: Anticipating the prospect of specific treatment, we studied a large
      group of Australians with Fabry's disease. AIMS: We aimed to: (i) document the
      clinical features of Fabry's disease in Australian patients, (ii) test the
      hypothesis that clinical features vary with specific mutation and blood group and
      (iii) assess small-fibre peripheral nerve function. METHODS: A questionnaire was
      forwarded to all Australian patients known to us. Patients were invited to attend
      for clinical, renal cardiac, ophthalmological and neurological assessment.
      RESULTS: Sixty-seven patients (29 men and 38 women) from 18 families
      participated. Diagnosis in index cases was delayed by > or = 10 years in nearly
      all families. Common clinical features are: (i) episodic acroparaesthesia (100%
      of hemizygotes; 53% of heterozygotes), (ii) anhydrosis (93%; 1%), (iii)
      characteristic rash (93%; 13%), (iv) renal disease (69%; 21%), (v) ischaemic
      heart disease (28%; 26%), (vi) palpitations (62%; 29%), (vii) mitral valve
      murmurs (37%; 23%) and (viii) premature cerebrovascular disease (31%; 5%).
      Ophthalmic findings of cornea verticillata (96%; 76%) and anterior cataract (48%;
      14%) were common. Findings were variable within and between families. In women,
      anhydrosis reliably predicts the presence of significant Fabry's renal disease.
      Small nerve fibre testing using quantitative sensory testing was clearly abnormal
      in 95% of male patients, and in those female patients with paraesthesiae.
      CONCLUSIONS: Symptoms of anhydrosis, acroparaesthesiae, rash and renal disease
      suggest diagnosis of Fabry's. Women are commonly symptomatic, and the advent of
      therapy highlights the practical advantage of earlier diagnosis.

PMID- 12512751
TI  - Evaluation of health-care worker vaccination in a tertiary Australian hospital.
AB  - BACKGROUND: Maintaining a complete vaccination status for health-care workers
      (HCWs) is important to minimize morbidity among staff and patients. Despite
      recommendations from public-health authorities to support this process, not all
      hospitals have adequate policy and practice in place. AIMS: To independently
      assess the implementation and impact of a new policy aimed at improving HCW
      vaccination coverage in a tertiary Victorian hospital. METHODS: Two cross
      sectional surveys were conducted by telephone in July and October 2000 for a
      random sample of HCWs, before and after the introduction of the policy. These
      surveys examined knowledge, attitudes and practices surrounding vaccination and
      self-reported vaccination status. Policy implementation was assessed by
      ascertaining completion of compulsory vaccination status forms and attendance at
      suggested appointments to review vaccination status. RESULTS: Only 19% of 269
      HCWs reported a complete vaccination status at baseline. Most (76%) had not heard
      of or seen vaccination guidelines and 39% kept written vaccination records. This
      was despite a belief in the importance of vaccination (94%) and a willingness to
      update if necessary (96%). At follow up there was no improvement in any outcome.
      Only 11/26 (42%) newly employed HCWs surveyed received and returned compulsory
      vaccination status forms. Of the few HCWs who attended recommended vaccination
      appointments, all received vaccinations. CONCLUSIONS: HCW vaccination coverage
      and knowledge of vaccination requirements were poor. Although attending a
      physician to discuss vaccination status did result in vaccination, few HCWs made
      such an appointment. While policy development is an important first step towards
      improving vaccination coverage, effective implementation requires ongoing
      evaluation, adequate resources and HCW education.

PMID- 12512752
TI  - Why do we need clinical practice improvement? A consumer perspective.

PMID- 12512753
TI  - Prevention of myocardial infarction.
AB  - Despite the rapid advances that have been made in the treatment of coronary
      artery disease, myocardial infarction remains the major cause of death in the
      developed world and a growing problem for developing countries. To address this
      growing problem, a strategy aimed at prevention of events in high-risk
      individuals is required. This involves assessment of cardiovascular risk followed
      by risk reduction. At present there is no perfect technique available for risk
      prediction, although computed tomography and magnetic resonance imaging scanning,
      along with serum markers of inflammation, offer the greatest potential. The
      applicability of these techniques at present is also limited by cost and
      accessibility. Risk reduction is possible through lifestyle changes and drug
      therapy, and effective risk assessment is essential in selecting those most
      likely to benefit from these interventions.

PMID- 12512754
TI  - Clinical and experimental uses of umbilical cord blood.
AB  - Umbilical cord blood (UCB) has been used successfully as an alternative source of
      haemopoietic stem cells (HSC) in allogeneic stem-cell transplantation for the
      treatment of acquired and genetic diseases. Advantages of using UCB include: (i)
      no risk to the donor, (ii) no donor attrition, (iii) minimal risk of viral
      transmission and (iv) immediate availability. Early results have highlighted
      differences in engraftment rates and toxicity between UCB and other sources of
      HSC. These differences relate to the low cell dose in UCB and also to the
      intrinsic properties of UCB. In this article, the clinical outcome of UCB
      transplantation (UCBT) will be reviewed with a discussion of the biological
      characteristics of UCB that may account for some of the clinical outcomes. To
      overcome the limitations of low cell dose, novel approaches such as ex vivo
      expansion of HSC are being actively explored, and this will be summarized in the
      present study. Finally, the success of UCBT has led to the establishment of
      dedicated UCB banks worldwide and the regulatory issues surrounding this will be
      briefly discussed.

PMID- 12512755
TI  - Variability in administration of 5-fluorouracil and folinic acid in standard
      treatment regimens for advanced colorectal cancer.

PMID- 12512756
TI  - Giant left main coronary artery aneurysm: an unusual cause of acute myocardial
      infarction.

PMID- 12512757
TI  - Renin-angiotensin system inhibition: how much is too much of a good thing?
AB  - Inhibitors of the renin-angiotensin system (RAS) are valuable therapeutic agents
      for a wide range of clinical conditions. Increasingly, consideration is being
      given to the combination of angiotensin-converting enzyme (ACE) inhibitors and
      angiotensin-II receptor (AR) antagonists to obtain more complete inhibition of
      the RAS than can be achieved by either agent alone. Beta-blockers also inhibit
      the RAS by inhibiting renin secretion. Whereas the combination of an ACE
      inhibitor and AR antagonist represents dual RAS inhibition, the combination of
      both of these agents with beta-blocker therapy represents triple RAS inhibition.
      Animal studies indicate that complete blockade of the RAS produces adverse
      effects. Moreover, post-hoc analysis of the recent Valsartan Heart Failure Trial
      study suggests that the combination of ACE inhibitor and AR antagonist therapies
      may have an adverse effect in heart failure when combined with beta-blocker
      therapy. There is therefore a need for caution in the combination of ACE
      inhibition and AR antagonism, particularly in patients receiving beta-blockers,
      until the impact of this strategy is evaluated.

PMID- 12512758
TI  - Prolonged survival in a patient with an occult primary small-cell lung cancer and
      a solitary brain metastasis at diagnosis.

PMID- 12512759
TI  - Primary alveolar hypoventilation and response to the respiratory stimulant
      almitrine.

PMID- 12512760
TI  - Acute pancreatitis: a rare complication of celecoxib.

PMID- 12512761
TI  - Treatment of acquired haemophilia.

PMID- 12512762
TI  - Pregnancy and women's lives in the twenty-first century: the United States Safe
      Motherhood movement.

PMID- 12512763
TI  - Safe motherhood in the United States: challenges for surveillance.
AB  - OBJECTIVES: Maternal mortality ratios in the United States are higher than those
      of many other industrialized nations. Moreover, these ratios have not changed in
      the past 20 years, and large racial disparities persist in measures of both
      maternal mortality and morbidity. In an affluent developed country, maternal
      deaths should serve as rare sentinel events, highlighting opportunities for
      prevention and reduction of morbidities. However, existing surveillance efforts
      are poorly developed, and pregnancy-related deaths and illnesses tend to be
      underreported. To formulate recommendations for improved surveillance, the
      authors reviewed existing data on maternal health. METHODS: This review examines
      the scope and quality of existing information and the strengths and limitations
      of definitions of maternal mortality and morbidity used in data collection and
      reporting. RESULTS: This review suggests numerous gaps in surveillance of U.S.
      maternal health. Psychological as well as physical morbidity, and the presence
      and adequacy of appropriate treatment, should be ascertained. Quality of
      pregnancy-related care at the clinical and community levels, and the impact on
      mortality and morbidity, must be assessed. Collection of morbidity data outside
      of health care delivery sites is also essential. Trade-offs between nationally
      representative and other less comprehensive data sources, such as sentinel
      clinics, large healthcare organizations, and public healthcare financing systems,
      should be considered. CONCLUSION: Maternal health remains an important frontier
      for U.S. public health surveillance efforts. Improved surveillance offers
      opportunities for reducing pregnancy-related mortality and gaining a better
      understanding of the relationship between maternal morbidity and mortality.

PMID- 12512764
TI  - Surveillance in a time of changing health care practices: estimating ectopic
      pregnancy incidence in the United States.
AB  - OBJECTIVES: Ectopic pregnancy is a common condition with significant health
      consequences; complications are a major cause of maternal mortality in the United
      States. Accurate ascertainment of the number of ectopic pregnancies occurring in
      the United States has been dramatically affected by changing medical practices,
      causing estimates based on hospital data to be falsely low. This study was
      performed to identify nationally representative data on ectopic pregnancies and
      determine overlap of these data, to calculate the annual weighted number of
      ectopic pregnancies and confidence intervals for these estimates, and to
      determine barriers to estimation of ectopic pregnancy incidence. METHODS: To
      assess whether a national estimate of the incidence of ectopic pregnancy could be
      calculated, we analyzed 1992-99 data from the six nationally representative data
      sets that include information on ectopic pregnancy. We examined relevant data in
      each data set and assessed whether any combination of data sets could be used to
      estimate ectopic pregnancy incidence. We calculated weighted estimates and 95%
      confidence intervals for hospitalizations, outpatient surgeries, outpatient
      medical procedures, and physician visits for and self-reports of ectopic
      pregnancy. RESULTS: Small sample sizes severely limited calculation of estimates
      of ectopic pregnancy. Data needed for assessing multiple counting was not
      available consistently. The likelihood of multiple counting of cases was
      substantial when data set counts were combined. CONCLUSIONS: A reliable incidence
      rate for ectopic pregnancy in the United States could not be estimated from
      existing nationally representative data sources. Major advances in diagnosis and
      treatment of ectopic pregnancy have affected surveillance in two ways: inpatient
      hospital treatment of ectopic pregnancy has decreased, and multiple health care
      visits for a single ectopic pregnancy have increased. Alternate means of
      surveillance are needed to improve understanding of risk factors and trends for
      ectopic pregnancy, and we recommend examination of the databases of public and
      private insurance systems and managed care systems. Similar alternate means of
      surveillance may be needed for other health conditions with comparable changes in
      management of care.

PMID- 12512765
TI  - Socioeconomic and racial/ethnic disparities in unintended pregnancy among
      postpartum women in California.
AB  - OBJECTIVE: We examined social disparities in unintended pregnancy among
      postpartum women to better understand 1) the role of socioeconomic factors in
      racial/ethnic disparities and 2) factors that might explain both socioeconomic
      and racial/ethnic disparities in the risk for unintended pregnancy among women
      who give birth. METHODS: We used 1999 and 2000 data from a statewide
      representative mail and telephone survey of postpartum women in California (N =
      7044). We examined associations between unintended pregnancy and race/ethnicity
      (African American, Asian or Pacific Islander, U.S.-born Latina, foreign-born
      Latina, European or Middle Eastern), three socioeconomic factors (poverty status,
      maternal education, paternal education), and several potential explanatory
      factors. RESULTS: Overall, racial/ethnic disparities in unintended pregnancy were
      reduced by the three socioeconomic factors individually and collectively (e.g.,
      reducing higher unadjusted odds for African Americans from 3.4 to 1.9);
      additional adjustment for marital status age, parity, insurance, language, abuse,
      sense of control, and interaction between marital status and race/ethnicity (each
      independently associated with unintended pregnancy) reduced the socioeconomic
      disparities (e.g., reducing odds for the poorest women from 4.1 to 2.3). Although
      reduced, significant racial/ethnic and socioeconomic disparities remained after
      adjustment, but generally only among married women. Results for Latinas appeared
      to vary by nativity, with foreign-born Latinas being at lower odds and U.S.-born
      Latinas being at higher odds of unintended pregnancy. CONCLUSIONS: Racial/ethnic
      disparities in unintended pregnancy are partly explained by the socioeconomic
      factors we measured. Several additional factors were identified that suggest
      possible directions for policies and programs to help reduce social disparities
      in unintended pregnancy among childbearing women.

PMID- 12512766
TI  - Correlates of self-reports of being very depressed in the months after delivery:
      results from the Pregnancy Risk Assessment Monitoring System.
AB  - OBJECTIVE: This study identified correlates of self-reports of being very
      depressed in the months after delivery in a population-based sample of women.
      METHODS: We analyzed data on 14,609 recent mothers from the Centers for Disease
      Control and Prevention's (CDC) Pregnancy Risk Assessment Monitoring System
      (PRAMS). The sample included mothers who delivered a live birth in Colorado, New
      York State, and North Carolina from 1996 (New York only) to 1999. We assessed
      risk factors for self-reports of being very depressed in the months after
      delivery using logistic regression. RESULTS: Overall, 5.9% (95% CI = 5.3, 6.4) of
      new mothers reported being very depressed in the months after delivery. Women who
      reported that their pregnancy was a "very hard time" or "one of the worst times
      of my life" had the highest prevalence of reporting being very depressed in the
      months after delivery (24.9%, 95% CI = 21.3, 28.5) and, when all risk factors
      were adjusted for simultaneously, were 4.6 times (95% CI = 3.1, 6.3) more likely
      to report being very depressed in the months after delivery than other women.
      Other significant risk factors for self-reports of being very depressed in the
      months after delivery included experiencing partner-associated stress (OR = 1.9,
      95% CI = 1.5, 2.5), physical abuse during pregnancy (OR = 1.6, 95% CI = 1.1,
      2.4), and not breast-feeding (OR = 1.4, 95% CI = 1.1, 1.8). CONCLUSIONS: The
      highest prevalence for self-reports of being very depressed in the months after
      delivery was in women who reported that their pregnancy was a "very hard time" or
      "one of the worst times of my life." Clinicians need to be aware of the needs of
      some women for mental health services both during and after pregnancy.

PMID- 12512767
TI  - Insulin and the "thrifty" woman: the influence of insulin during pregnancy on
      gestational weight gain and postpartum weight retention.
AB  - OBJECTIVES: To test Neel's hypothesis among pregnant women: a high maternal
      insulin concentration in early pregnancy increases the risk of weight gain,
      overweight, and obesity among nondiabetic, low-income gravidas of racial and
      ethnic minority groups from Camden, New Jersey. METHODS: Fasting insulin was
      obtained from 461 gravidas at entry to prenatal care. Insulin quartile was
      related to rate of gestational weight gain and excess weight gain during
      pregnancy (> or = 90th percentile) and to retained weight and excess weight
      retention at 4-6 weeks postpartum (> or = 90th percentile). The relationship
      between excess retained weight and excessive insulin increase (> or = 90th
      percentile) was also examined. RESULTS: Compared with gravidas with an insulin
      concentration in the lowest three quartiles, gravidas with the highest insulin
      quartile had a significantly higher rate of gestational weight gain (nonobese
      women only) and average weight retained postpartum (all women). Compared with an
      insulin concentration in the lowest three quartiles, the highest insulin quartile
      was associated with a 2.05-fold (95% confidence interval [CI] = 1.07-3.93) risk
      of an excessive rate of gestational weight gain and a 3.58-fold (95% CI = 1.87
      6.84) risk of excess weight retained postpartum. Excess weight retained
      postpartum was linked to a 2.63-fold (95% CI = 1.00-6.89) risk of an excessive
      increase in insulin concentration postpartum. CONCLUSIONS: Our results support
      Neel's hypothesis and suggest that a high maternal insulin concentration is
      associated with increased gestational weight gain and increased weight retention
      postpartum. High insulin concentration may contribute to pregnancy-related
      changes in weight and thus may be linked to maternal overweight and obesity
      postpartum as well as to future risk of gestational and Type 2 diabetes mellitus.

PMID- 12512768
TI  - Evaluation of maternal death surveillance: a community process.
AB  - The Mississippi State Department of Health found that the Centers for Disease
      Control and Prevention guidelines for evaluating surveillance systems could be
      used as a community approach in changing a maternal mortality surveillance
      system. This experience caused us to think more broadly about maternal mortality,
      challenge the guideline process, and ultimately embark on a new surveillance
      system. System changes included ensuring dissemination of findings, increasing
      number and type of stakeholders, including nonmedical factors, heightening
      awareness of maternal mortality, promoting timely reviews, reviewing our
      regulatory authority, adding field staff notification about maternal deaths,
      expanding the definition of maternal death, and combining surveillance systems
      all of which leads to improved maternal mortality surveillance in Mississippi.

PMID- 12512769
TI  - Safe motherhood: values, purpose, and possibility.

PMID- 12512770
TI  - Non-permanent proteins in membranes: when proteins come as visitors (Review).
AB  - The present review introduces the concept of 'non-permanent membrane proteins',
      to encompass the wide variety of proteins that are not found in a stable membrane
      bound form under physiological conditions, yet they interact with the membrane at
      some stage of their specific course of action. Non-permanent membrane proteins
      can be codified by the cell's own genome, or else they may arise from a foreign
      genome. Non-permanent membrane proteins can be classified, according to the
      reversibility of the membrane interaction, into those with reversible and
      irreversible (very long-lived) membrane contacts. According to the nature
      (strength) of the interaction, non-permanent membrane proteins may be divided
      into those that interact weakly with the membrane, in an extrinsic-like form, and
      those that interact strongly with the membrane. The latter can in turn be
      classified into those that cause and those that do not cause covalent
      modification of the lipids, the latter behaving, after interacting with the
      membrane, in the way of the conventional intrinsic proteins. Multiple examples
      are provided for the different groups of non-permanent membrane proteins, and a
      more detailed description is given of three of them, representative of different
      groups, namely TrwD from plasmid R388, E. coli alpha-haemolysin and B. cereus
      sphingomyelinase.

PMID- 12512771
TI  - Interaction of membrane-spanning proteins with peripheral and lipid-anchored
      membrane proteins: perspectives from protein-lipid interactions (Review).
AB  - Studies of lipid-protein interactions in double-reconstituted systems involving
      both integral and peripheral or lipid-anchored proteins are reviewed. Membranes
      of dimyristoyl phosphatidylglycerol containing either myelin proteolipid protein
      or cytochrome c oxidase were studied. The partner peripheral proteins bound to
      these membranes were myelin basic protein or cytochrome c, respectively. In
      addition, the interactions between the myelin proteolipid protein and avidin that
      was membrane-anchored by binding to N-biotinyl phosphatidylethanolamine were
      studied in dimyristoyl phosphatidylcholine membranes. Steric exclusion plays a
      significant role when sizes of the peripheral protein and transmembrane domain of
      the integral protein are comparable. Even so, the effects on avidin-linked lipids
      are different from those induced by myelin basic protein on freely diffusible
      lipids, both interacting with the myelin proteolipid protein. Both the former and
      the cytochrome c/cytochrome oxidase couple evidence a propagation of lipid
      perturbation out from the intramembrane protein interface that could be a basis
      for formation of microdomains.

PMID- 12512772
TI  - Internal water molecules of archaeal rhodopsins (Review).
AB  - Archaeal rhodopsins possess retinal molecule as their chromophores, and their
      light-energy and light-signal conversions are triggered by all-trans to 13-cis
      isomerization of the retinal chromophore. Relaxation through structural changes
      of protein then leads to functional processes, light-driven ion pump or
      transducer activation. Internal water molecules were considered to play an
      important role in the functional processes of archaeal rhodopsins, although
      limited information has been obtained about the structure and function of
      internal water molecules. Recent progress in Fourier-transform infrared (FTIR)
      spectroscopy and X-ray crystallography provided new information of water
      molecules inside archaeal rhodopsins. This article reviews studies on internal
      water molecules of archaeal rhodopsins by means of low-temperature FTIR
      spectroscopy.

PMID- 12512773
TI  - Direct studies of ligand-receptor interactions and ion channel blocking (Review).
AB  - Small molecules can activate membrane bound receptors to elicit cellular
      responses and approximately 80% of all such responses are mediated through
      membranes. Solid state nuclear magnetic resonance (NMR) methods have been
      developed for the resolution of specifically labelled ligands, designed to report
      back structural, dynamic and electronic details of the ligand whilst at its site
      of action. In particular, ion channel blockers, drugs, inhibitors, prosthetic
      groups and solutes have been studied when at their target site in functionally
      competent membranes. A blocker of the channel in the anion transporter of
      erythrocytes (AE1) has been studied to show that considerable motional freedom
      within the channel site occurs. The activating agonist of the ligand gated ion
      channel, the nicotinic acetylcholine receptor, is constrained at its site of
      action and binds through a cation-pi interaction as revealed in the NMR spectra.
      The footprint for the inhibitor binding site of the digitalis receptor, the
      Na(+)/K(+)-ATPase has been resolved as well as the molecular conformation of
      digitalis showing a bent structure whilst at its site of action. For the gastric
      proton pump, however, a planar conformation is observed for a reversible
      substituted imidazopyridine. In all cases not only the structure, but also some
      indications about the electronic interactions of ligand and target have been
      resolved using these approaches.

PMID- 12512774
TI  - Lipid matters: nicotinic acetylcholine receptor-lipid interactions (Review).
AB  - Ligand-gated ion channels mediate fast intercellular communication in response to
      endogenous neurotransmitters. The nicotinic acetylcholine receptor (AChR) is the
      archetype molecule in the superfamily of these membrane proteins. Early electron
      spin resonance studies led to the discovery of a lipid fraction in direct contact
      with the AChR, with rotational dynamics 50-fold slower than those of the bulk
      lipids. This AChR-vicinal lipid region has since been postulated to be a possible
      site of lipid modulation of receptor function. The polarity and molecular
      dynamics of solvent dipoles-mainly water-of AChR-vicinal lipids in the membrane
      have been studied with Laurdan extrinsic fluorescence, and Forster-type resonance
      energy transfer (FRET) was introduced to characterize the receptor-associated
      lipid microenvironment. FRET enabled one to discriminate between the bulk lipid
      and the AChR-vicinal lipid. The latter is in a liquid-ordered phase and exhibits
      a higher degree of order than the bulk bilayer lipid. Changes in FRET efficiency
      induced by fatty acids, phospholipids and cholesterol also led to the
      identification of discrete sites for these lipids on the AChR protein. After
      delineating the topography of the AChR membrane-embedded domains with
      fluorescence methods, sites for steroids are being explored with site-directed
      mutagenesis and patch-clamp recording. Pyrene-labelled Cys residues in alphaM1,
      alphaM4, gammaM1 and gammaM4 transmembrane regions were found to lie in a shallow
      position. For M4 segments, this is in agreement with a canonical linear alpha
      helix; for M1, it is necessary to postulate a substantial amount of non-helical
      structure, and/or of kinks, to rationalize the shallow location of Cys residues.
      Mutations of Thr422, a residue close to the extracellular-facing membrane
      hemilayer in alphaM4, affect the steroid modulation of AChR function, suggesting
      its involvement in steroid-AChR interactions.

PMID- 12512775
TI  - Mechanisms of block of muscle type CLC chloride channels (Review).
AB  - CLC proteins are a nine-member gene family of Cl- channels that have diverse
      roles in the plasma membrane and in intracellular organelles. The recent
      structure determination of bacterial CLC homologues by Dutzler et al. was a
      breakthrough for the structure-function analysis of CLC channels. This review
      describes the mechanisms of inhibition of muscle type CLC channels by two classes
      of small organic substances: 9-anthracene carboxylic acid (9AC) and p
      chlorophenoxy propionic acid (CPP). Both substances block muscle type CLC
      channels (CLC-0 and CLC-1) from the intracellular side. For CPP, one could show
      that it inhibits the individual protopores of the double-barrelled channel. A
      major difference between the two types of blockers is the extremely slow binding-
      and unbinding-kinetics of 9AC (time scale of min), compared to that of CPP block
      (time scale of s), while the general mechanism of block seems to be quite
      similar. In the case of the chiral CPP only the S(-) enantiomer is effective.
      Both substances exhibit a strongly voltage-dependent block with strong inhibition
      at negative voltages and relief of block at depolarizing potentials at which the
      channels tend to open maximally. A quantitative kinetic model was developed for
      the CPP block of CLC-0 in which the closed state has a much larger affinity for
      CPP than the open state and opening of drug-bound channels is greatly slowed
      compared to drug-free channels. First experiments with mutated CLC-0 channels and
      with derivatives of CPP strongly support the pore localization of the CPP binding
      site. This work provides the basis for the use of these small organic substances
      as tools to investigate the pharmacological properties of mammalian CLC channels
      guided by the crystallographic structure of bacterial CLC homologues. They might
      also turn out to be useful to obtain information about the intricate coupling of
      gating and permeation that characterizes CLC channels.

PMID- 12512776
TI  - Calcium channels involved in neurotransmitter release at adult, neonatal and P/Q
      type deficient neuromuscular junctions (Review).
AB  - Different types of voltage-dependent calcium channels (VDCCs) have been
      recognized based on their molecular structure as well as their pharmacological
      and biophysical properties. One of these, the P/Q type, is the main channel
      involved in nerve evoked neurotransmitter release at neuromuscular junctions
      (NMJs) and many central nervous system synapses. However, under particular
      experimental or biological conditions, other channels can be involved. L-type
      VDCC presence at the NMJ has been demonstrated by the contribution to the
      perineural calcium currents (Ica) at adult mice Bapta-loaded NMJs. This is
      probably a result of a reduction in Ca(2+) inactivation. The L-type current was
      not coupled to neurotransmitter release, but became coupled, as demonstrated by
      the release of acetylcholine, after the inhibition of serine/threonine protein
      phosphatases with okadaic acid (OA). Thus, under these conditions, L-type
      channels were unmasked at Bapta- but not at Egta-loaded NMJs. This suggests that
      the speed, not the capacity, of the calcium chelator was decisive in preventing
      Ca(2+)-inactivation and facilitating the contribution to neurotransmitter
      release. At neonatal rat NMJs, N-type VDCCs were involved early during
      development whereas P/Q-type VDCCs play a main role at all stages of development.
      Furthermore, P/Q-type VDCCs were more efficiently coupled to neurotransmitter
      release than N-type VDCCs. This difference could be accounted for by a
      differential location of these channels at the release site. Neuromuscular
      transmission in P/Q-type calcium channel knock out ataxic mice jointly depends on
      both N-type and R-type channels and shows several altered properties including
      low quantal content. Thus, calcium channels may be recruited to mediate
      neurotransmitter release with a functional hierarchy where the P/Q channel seems
      to be the channel most suited to mediate exocytosis at NMJs.

PMID- 12512777
TI  - Thermogenesis and energy expenditure: control of heat production by the Ca(2+)
      ATPase of fast and slow muscle.
AB  - This report measured the amount of heat released during Ca(2+) transport and ATP
      hydrolysis by vesicles derived from the sarcoplasmic reticulum of rabbit slow
      (SM) and fast (FM) muscle. During ATP hydrolysis, part of the chemical energy
      released is used to translocate Ca(2+) through the membrane (work) and part is
      dissipated as heat. The amount of heat produced during catalysis increases after
      formation of the Ca(2+) gradient across the vesicle membrane. In the absence of
      gradient (leaky vesicles), the heat produced per mol of ATP cleaved by SM and FM
      vesicles was the same and varied between 7.7-9.1 kcal. In the presence of the
      gradient the heat produced by SM and FM vesicles differed, 13.4 kcal/mol and 23.0
      kcal/mol ATP cleaved, respectively. After formation of the gradient, part of the
      ATPase activity was not coupled to Ca(2+) transport. The difference of heat
      produced by FM and SM vesicles during ATP hydrolysis was related to the rate of
      uncoupled ATPase activity. When extended to the living cell, the data described
      indicate that the amount of heat produced by the Ca(2+)-ATPase of SM muscle is 36
      times smaller than that produced by the FM. Thyroid hormone 3,5,3'-triiodo L
      thyronine (T3) regulate both thermogenesis and the transcription of the
      sarcoplasmic reticulum Ca(2+)-ATPase isoforms found in SM and FM. The findings
      described in this report raise the possibility that one of the mechanisms of
      thermogenesis control may be related to the regulation of Ca(2+)-ATPase isoforms
      expression by T3.

PMID- 12512778
TI  - Mandibular outline assessment in three groups of orthodontic patients.
AB  - The feasibility of using computer-based parameters for quantifying mandibular
      asymmetry was investigated. Four methods of calculating asymmetry were used,
      based on the digitized facial photographs of three groups of patients: those with
      no observable asymmetry, a group with mild asymmetry, and a group presenting for
      orthognathic surgery. Three of the methods involved right/left difference ratios,
      namely, area, perimeter length, and compactness. The fourth, moment ratio (centre
      of area), was expressed as a percentage. Repeatability of both photography and
      digitization proved satisfactory, the standard deviation of the differences
      between repeated photographs being 0.016 and 0.014 for area and compactness
      ratios, respectively. Area, perimeter, and compactness successfully discriminated
      between the three groups. For area, median ratios (deviations from 1.00) for the
      'normal', 'mild asymmetry', and 'surgical' groups were 0.015, 0.030, and 0.078,
      respectively. Those patients in the surgical group for whom asymmetry correction
      had been the main reason for surgery recorded higher asymmetry scores than the
      other subjects in that group. Moment ratio did not adequately distinguish between
      the three groups. Better repeatability for digitization was found when a baseline
      involving the ear insertions was used, than either the outer or inner canthi of
      the eyes. The potential uses of this approach are presented in relation to
      clinically relevant mild asymmetry, as well as auditing the outcome of surgical
      correction.

PMID- 12512779
TI  - Sagittal occlusal relationships and asymmetry in prematurely born children.
AB  - The aim of this investigation was to examine the effect of pre-term birth on
      sagittal occlusal relationships. The subjects were 328 prematurely born white and
      black children and 1804 control children who participated in the cross-sectional
      study of the Collaborative Perinatal Project (USA) in the early 1960s and 1970s.
      Dental examinations, including dental casts and photographs, were performed at
      the age of 6-12 years. The sagittal occlusion of the permanent molars and the
      canine relationship was recorded by examining and measuring the hard stone casts.
      The pre-term and comparison groups were divided by sex and race. A significantly
      greater prevalence of pre-normal canine relationships was found in the pre-term
      group than in the controls (P < 0.001). The incidence of a bilateral symmetrical
      canine relationship was 60.3 per cent in both the pre-term and control groups,
      but in the pre-term group the girls had better symmetry than the boys. Asymmetry
      occurred significantly more often on the left side (P < 0.001), especially in the
      control boys, but this was not so clear in the pre-term group. The prevalence of
      mesial molar occlusion was greater in the pre-term group. These results suggest
      that premature birth and the consequent exceptional adaptation from intra- to
      extra-uterine nutrition may influence dental occlusal development. This
      emphasizes the importance of early functional activity and differences in
      masticatory muscle activity and the largely unknown phenomenon of early catch-up
      growth. Individual differences in neonatal factors, in the need for intubation
      and other medical care are also of importance. Pre-term birth may also interfere
      with the development of symmetry and lateralization.

PMID- 12512780
TI  - Effective temporomandibular joint growth and chin position changes: Activator
      versus Herbst treatment. A cephalometric roentgenographic study.
AB  - In 138 successfully treated Class II division 1 patients (40 Activator and 98
      Herbst) effective temporomandibular joint (TMJ) growth changes (a summation of
      condylar remodelling, glenoid fossa remodelling, and condylar position changes
      within the fossa), and their influence on the position of the chin and the
      rotation of the mandible were analysed retrospectively. Lateral head films in
      habitual occlusion from before and after an average treatment period of 2.6 years
      for the Activator patients and 0.6 years for the Herbst patients were evaluated.
      Two different treatment changes were assessed: (1) overall growth changes and (2)
      treatment effects (overall growth changes minus age-related normal growth values:
      Bolton Standards). The comparison between the Activator and the Herbst group
      revealed larger effective TMJ and chin changes during Activator therapy due to
      the longer observation period (2.6 years versus 0.6 years). The treatment effects
      showed marked group differences for both the amount and direction of effective
      TMJ changes. The changes were vertical and slightly anterior in the Activator
      group, and predominantly posterior in the Herbst group. Concerning the chin
      changes, the treatment effects for the Herbst group exceeded those for the
      Activator group in both directions, caudally and anteriorly. The Activator group
      showed an anterior rotation and the Herbst group a slight posterior rotation of
      the mandible. The present investigation revealed that the effective TMJ and chin
      changes were increased by both Activator and Herbst treatment. However, the
      Herbst appliance renders more favourable sagittally orientated treatment effects
      in a much shorter period of time compared with the Activator.

PMID- 12512781
TI  - Moulding of the generate to control open bite during mandibular distraction
      osteogenesis.
AB  - Distraction osteogenesis of the craniofacial skeleton has become a widely
      accepted, safe, and effective means of craniofacial reconstructive surgery.
      Despite excellent results in general, there are still some uncertainties related
      to the procedure, such as development of an anterior open bite (AOB) during
      mandibular distraction. The aim of this study was to examine whether 'moulding of
      the generate', i.e. use of intermaxillary elastics during the active distraction
      phase is possible to close the mandibular plane angle and open bite. Three
      subjects, 13- and 15-year-old males and a 7-year-old female, underwent mandibular
      linear and angular bilateral distraction osteogenesis with moulding of the
      generate. Lateral cephalograms were obtained before the introduction of elastics
      and following distraction, once the activation was stopped and the patients were
      ready for the consolidation phase. Conventional cephalometric measurements were
      used to assess possible changes in the mandibular plane angle and incisor
      position. Three different anchorage systems (dental, orthopaedic, and skeletal)
      were used for placement of the intermaxillary elastics. Cephalometric examination
      showed that the mandibular plane angle was decreased during active distraction
      osteogenesis with the introduction of elastics and angulation of the distraction
      device. Depending on the type of elastic anchorage system, smaller or greater
      amounts of extrusion of the incisors were noted. Moulding of the generate during
      active distraction can be performed to reduce the mandibular plane angle and open
      bite. To prevent unwanted dentoalveolar changes from occurring during elastic
      traction, skeletal rather than dental fixation of the elastics is recommended.
      Intrusive mechanics may be incorporated into the orthodontic appliances to
      balance extrusive force by the moulding elastics.

PMID- 12512782
TI  - Cleft type and Angle's classification of malocclusion in Korean cleft patients.
AB  - This study was performed to investigate the contributing factors, such as cleft
      type, side of cleft, patient's age, and gender, associated with Angle's
      classification of malocclusion in Korean cleft patients. The records of 250 cleft
      patients (175 males, 75 females) who attended the Department of Orthodontics,
      Seoul National University Dental Hospital between 1988 and 1999 were examined.
      The percentages of subjects with cleft lip (CL), cleft lip and alveolus (CLA),
      cleft palate (CP), and cleft lip and palate (CLP) were 7.6, 19.2, 9.6, and 63.6,
      respectively. The overall distributions of unilateral and bilateral clefts were
      76 and 24 per cent, respectively. The overall percentages of Class I, II, and III
      malocclusions were 18.5, 8.8, and 72.7. The frequency of Class III malocclusions
      was most prevalent in all age groups. Bivariate analysis showed that whilst
      gender was not significant, the type of cleft significantly influenced the
      development of a Class III malocclusion (P < 0.01). Using logistic regression
      analysis, subjects in the CP (P < 0.05) and CLP groups (P < 0.01) were 3.9 and
      5.5 times more likely to have a Class III malocclusion than those in the CL
      group. There was, however, no statistical difference in the prevalence of a Class
      III malocclusion between the CL and the CLA groups (P > 0.05). When the degree of
      cleft involvement in the palate increased, so did the predominance of a Class III
      malocclusion.

PMID- 12512783
TI  - The reproducibility of cephalometric measurements: a comparison of analogue and
      digital methods.
AB  - The aim of this study was to compare the reproducibility of longitudinal
      cephalometric measurements between analogue and digital methods using two
      different resolutions. Cephalometric radiographs of 20 patients were selected at
      the start (T1) and end (T2) of treatment: 24 cephalometric variables were
      calculated at T1 and T2, and their increments (T2 - T1) were also evaluated. All
      measurements were performed twice by two observers. Quality of methods [analogue,
      digital: 300 and 600 dots per inch (DPI) resolution] was evaluated by comparing
      the reliability coefficients and the total error between the digital and analogue
      methods. The inter-observer agreement was good. The 300 DPI was comparable to the
      analogue method. The reproducibility for the variables was comparable, but
      mandibular incisor increments tended to show better results with the 300 DPI
      method, whereas skeletal jaw relationship increments were not reliable with
      either method. Maxillary incisor increments, however, were reliable with both
      methods. The 300 and 600 DPI resolutions were found to be comparable. Scanning of
      cephalometric radiographs at a resolution of 300 DPI is sufficient for clinical
      purposes and comparable to analogue cephalometrics. However, all methods were
      found to be poor in assessing skeletal jaw relationships longitudinally.

PMID- 12512784
TI  - The effect of maceration on the dental arches and the transverse cranial
      dimensions: a study on the pig.
AB  - The dimensional change of the dental arches and the transverse cranial dimensions
      were studied in the pig to gain information on cranial post mortem changes and
      thus improve the possibilities of comparison between modern and skeletal samples.
      Dental arch dimensions were registered in 17 pigs within 30 minutes after they
      had been killed. The following day, the skulls were registered on lateral and
      axial radiographs. The animals were prepared, and storage and preparation
      included freezing and treatment in hot water. The water temperature did not
      exceed 65 degrees C. After this process, the skulls were again registered on
      lateral and axial radiographs. The skulls were then allowed to dry for 2 weeks
      and the direct measurements were repeated. The dimensions showed shrinkage of
      between 0 and 3.3 per cent. The mandible showed a greater change transversally in
      the posterior region than the cranium, which may have been due to its shape. The
      more deviant values for dimensional change were probably due to technical errors
      and the shrinkage may be expected to vary from 0.3 to 1.7 per cent, with greater
      values occurring in the posterior transverse parts of the mandible. A
      differential shrinkage in the maxilla could not be excluded and the values varied
      between 0.3 and 1.9 per cent. The results indicate that the crania in skeletal
      samples can be expected to be 0.3-1.7 per cent smaller than in vivo.

PMID- 12512785
TI  - Occlusal interferences in orthodontic patients before and after treatment, and in
      subjects with minor orthodontic treatment need.
AB  - Different opinions have been expressed concerning the effect of orthodontic
      treatment on mandibular function. One factor discussed is occlusal interferences.
      The aim of this study was to establish the prevalence of occlusal interferences
      in 210 orthodontic patients before (mean age 12 years 8 months) and after (mean
      age 16 years 10 months) treatment and to compare them with subjects with minor
      orthodontic treatment need. The results showed a decrease in retruded contact
      position/intercuspal position (RCP/ICP) interferences in all morphological
      deviations, age, and gender groups. The prevalence of mediotrusion interferences
      decreased in some types of malocclusions whilst in others there was no change.
      One reason for this is that treatment was started when the majority of the
      patients had no second or third molars erupted. At the final registration, the
      second molars were erupted in all patients, and the third molars were erupted in
      approximately 25 per cent. Mediotrusion interferences were more consistent with
      basal morphological deviations, for example, Class III relationships and anterior
      open bite were more consistent in the same person, and more difficult to
      eliminate than RCP/ICP interferences. RCP/ICP interferences, often caused by
      dental deviation in position, size, and shape, were easier to correct. Optimal
      orthodontic treatment, if necessary, including selective grinding, will decrease
      the prevalence of occlusal interferences.

PMID- 12512786
TI  - Polymerization with a micro-xenon light of a resin-modified glass ionomer: a
      shear bond strength study 15 minutes after bonding.
AB  - The purpose of this study was to evaluate the initial shear bond strength (15
      minutes after bonding) of a resin-modified glass ionomer (RMGIC, Fuji Ortho LC)
      cured with two different light-curing units: a conventional visible light
      (Ortholux XT) and a microxenon light (Aurys). Seventy-five freshly extracted
      bovine permanent mandibular incisors were randomly assigned to one of five
      groups; each group consisted of 15 specimens. Group A (Transbond XT) and group B
      (Fuji Ortho LC) were exposed to the visible light for 20 and 40 seconds,
      respectively, and used as controls. The remaining three groups (C, D, and E) were
      bonded with Fuji Ortho LC and cured with Aurys for 10, 5, and 2 seconds,
      respectively. All samples were tested in a shear mode on an Instron universal
      testing machine 15 minutes after bonding. The shear bond strength of the control
      group bonded with Transbond XT was significantly higher (P = 0.000) than those of
      all the other groups tested. Regarding Fuji Ortho LC, no statistically
      significant differences were found between the bond strength of the control group
      cured with Ortholux XT, and those of the groups cured with Aurys for 2, 5, and 10
      seconds. The present findings indicate that, compared with visible light-curing,
      the micro-xenon light enables the clinician to significantly reduce the curing
      time of RMGICs, without affecting their initial shear bond strengths.

PMID- 12512787
TI  - Uvulo-glosso-pharyngeal dimensions in subjects with beta-thalassaemia major.
AB  - The purpose of this study was to investigate cephalometrically the uvulo-glosso
      pharyngeal dimensions in subjects with beta-thalassaemia major. The subjects were
      15 thalassaemic patients (eight males, seven females) with a mean age of 14.13 +/
      1.06 years. The variables measured on the lateral cephalograms were tongue
      height and length, soft palate length and thickness, superior, middle and
      inferior pharyngeal airway space, and hyoid bone position. The thalassaemic group
      was compared with a normal control group matched for sex and age using a t-test.
      The results showed that thalassaemic patients had a smaller tongue size (length P
      < 0.05, height P < 0.001), shorter soft palate (P < 0.001), smaller upper (P <
      0.001) and middle (P < 0.05) pharyngeal airway spaces, and a shorter vertical
      pharyngeal length (P < 0.05). The hyoid bone in thalassaemic patients was closer
      to the mandibular plane (P < 0.001).

PMID- 12512788
TI  - The reliable measurement of radial pulse characteristics.
AB  - The use of the radial pulse as a diagnostic tool is an integral part of the
      Traditional Chinese Medicine (TCM) patient evaluation. In spite of its long
      history of use, there is little systematic information available to support the
      many claims about the relationship between pulse qualities and physiological
      condition contained in the ancient Chinese texts and echoed in modern pulse
      terminology. This study reports the development of a reliable means of measuring
      and recording pulse characteristics. This was achieved by reporting on the
      physical sensations that are detected under the fingertips when the radial pulse
      is palpated, rather than attempting to translate these into the complex and
      typically ambiguously defined TCM pulse qualities. The study involved development
      of a standardised pulse taking procedure and development of concrete operational
      definitions for each of the characteristics of the pulse being measured. The
      inter-rater reliability of the pulse taking procedure and operational definitions
      was assessed by determining agreement levels between two independent pulse
      assessors for each characteristic. Inter-rater agreement averaged 80% between the
      two assessors in both the initial data collection (66 subjects) and in a
      replication collection (30 subjects) completed two months later. Demonstrating
      reliability of the procedure represents an essential first step for examining the
      validity of TCM pulse diagnosis assumptions.

PMID- 12512789
TI  - The reliable measurement of radial pulse: gender differences in pulse profiles.
AB  - This study was undertaken to determine whether healthy adults exhibited
      characteristic pulse profiles. Pulse characteristics measured for 83 women and 65
      men included presence at the Traditional Chinese Medicine (TCM) locations (Cun,
      Guan, Chi); and depth (superficial, middle, deep), overall pulse force, relative
      pulse force, pulse width and pulse rhythm. Most subjects had similar values for
      many of the characteristics investigated including relative pulse force at the
      three traditional palpation locations (Cun, Guan and Chi), pulse width and pulse
      rhythm. There were some significant gender differences. The pulse was present
      beyond Chi in 90% of males compared with 56% of females. Female pulses tended to
      be less forceful compared with males. However, with the exception of overall
      force, there was little support for TCM assumptions of gender differences in
      pulse such as in left/right balance. There was some support for the use of the
      TCM palpation locations Cun, Guan and Chi to discriminate between pulses since
      there was significant differences in manifestations of some pulse characteristics
      among these locations.

PMID- 12512790
TI  - Validating a new non-penetrating sham acupuncture device: two randomised
      controlled trials.
AB  - For clinical trials of acupuncture, it would be desirable to have a sham
      procedure that is indistinguishable from the real treatment, yet inactive. A sham
      needle has been designed which telescopes instead of penetrating the skin. The
      Park Sham Device involves an improved method of supporting the sham needle and
      requires validation. The objective of these studies was to test whether the sham
      procedure using the new device was 1) indistinguishable from the same procedure
      using real needles in acupuncture naive subjects, and 2) inactive, where the
      specific needle sensation (de qi) is taken as a surrogate measure of activity.
      The studies were designed as subject and assessor blind, randomised controlled
      trials. Study 1) included 58 patients enrolled in a clinical trial of acupuncture
      for acute stroke. Study 2) included 63 healthy, acupuncture naive, adult
      volunteers. The interventions used were real or sham acupuncture using the Park
      Sham Device. Study 1) was set in a district general hospital, and study 2) in a
      university laboratory. The outcome measure in study 1) was the form of treatment
      that patients believed they had received. In study 2) the outcome measure was
      experience of de qi, as judged by three acupuncture experts. No patient in either
      group(study 1) believed he or she had been treated with the sham needle. In 40
      volunteers (study 2) for whom experts achieved consensus, the relative risk of
      experiencing de qi with real acupuncture to that with sham acupuncture was 15.38
      (95% CI 2.26 to 104.86). The inter-rater reliability of all 13 experts (study 2),
      calculated from their judgements on 10 subjects selected by randomisation, was
      0.52 (95% CI 0.19 to 0.61). In conclusion, the results suggest that the procedure
      using the new device is indistinguishable from the same procedure using real
      needles in acupuncture naive subjects, and is inactive, where the specific needle
      sensation (de qi) is taken as a surrogate measure of activity. It is therefore a
      valid control for acupuncture trials. The findings also lend support to the
      existence of de qi, a major concept underlying traditional Chinese acupuncture.

PMID- 12512791
TI  - Randomised controlled trial comparing the effectiveness of electroacupuncture and
      TENS for low back pain: a preliminary study for a pragmatic trial.
AB  - The objective of this study was to compare the effectiveness of
      electroacupuncture and TENS for low back pain when the electroacupuncture is
      applied in a clinically realistic manner. The study was designed as an evaluator
      blinded randomised controlled trial (RCT). The study was performed at the Tsukuba
      College of Technology Clinic in Japan. Twenty subjects, who suffered from low
      back pain (LBP) without sciatica, were recruited, using leaflets in Tsukuba city.
      Subjects were allocated to either an electroacupuncture (EA) group (10 patients)
      or a transcutaneous electrical nerve stimulation (TENS) group (10 patients). The
      procedure for EA was in accordance with standard practice at our clinic. The main
      outcome measures were a pain relief scale (100 mm visual analogue scale: VAS) and
      a LBP score recommended by the Japanese Orthopaedic Association (JOA Score). Mean
      VAS value during the 2-weeks experimental period of the EA group was
      significantly smaller than that of the TENS group (65 mm vs 86 mm; 95% CI, 4.126 
      37.953). JOA Score in the EA group improved significantly while that in the TENS
      group showed no change. Although some placebo effect may be included, EA appeared
      more useful than TENS in the short-term effect on low back pain. We suggest that
      more realistic acupuncture interventions based on standard practice should be
      employed in pragmatic RCTs.

PMID- 12512792
TI  - Acupuncture for tennis elbow: an E-mail consensus study to define a standardised
      treatment in a GPs' surgery.
AB  - Acupuncture is a possible alternative treatment for tennis elbow in general
      practice. Rigorous investigation of its effectiveness is needed by means of a
      randomised controlled trial. Before undertaking a trial, a consensus is required
      on the best treatment protocol. Therefore, a modified Delphi Process was
      undertaken by e-mail, consisting in three iterative rounds. Fourteen acupuncture
      trainers initially reported details of their normal treatment that were then
      incorporated into a treatment plan. This was circulated once for further
      suggestions and finally for agreement. Consensus was achieved from all 14
      participants who responded to the third round.

PMID- 12512793
TI  - Neurogenic pruritus: an unrecognised problem? A retrospective case series of
      treatment by acupuncture.
AB  - Intractable localised segmental pruritus without a rash has been reported over
      the years under various titles depending on the area of the body affected.
      Notalgia paresthetica and brachioradial pruritus are the two terms used for what
      is believed to be a form of neuropathy. The clinical observations reported here
      suggest that other localised cases of pruritus exist that share common clinical
      features, and the term neurogenic pruritus is suggested to encompass these under
      one clinical condition. Acupuncture has been used to treat skin conditions, of
      which pruritus is one symptom. This retrospective study looked at the symptomatic
      relief of neurogenic pruritus in 16 patients using acupuncture. In 12 cases the
      affected dermatomes of the body were innervated by cervical spinal nerves, seven
      innervated by dorsal spinal nerves and four innervated by the lumbar spinal
      nerves. Seven patients had areas affected by two different regions of the spine.
      Restricted neck or back movements were noted in patients as were areas of
      paravertebral spasm or tenderness of the muscles. Total resolution of symptoms as
      judged by VAS occurred in 75% of patients. Relapse occurred in 37% of patients
      within 1-12 months following treatment. Acupuncture appeared to be effective in
      alleviating the distressing symptom of itching in patients presenting with
      neurogenic pruritus.

PMID- 12512794
TI  - Acupuncture treatment of pain dysfunction syndrome after dental extraction.
AB  - A successful treatment with acupuncture of a patient with Pain Dysfunction
      Syndrome is presented. The patient developed restricted mouth opening after
      removal of a third molar in the lower jaw. Despite orthodox treatment no
      improvement was noticed after three months, and his general practitioner was
      contacted. After two acupuncture sessions the patient felt normal and the jaw
      movement was within the normal range. A follow-up four weeks after the first
      treatment showed a further increase in the jaw movement. If restricted movement
      in the temporomandibular joint occurs after operative procedures in the mouth,
      acupuncture should be considered at an early stage.

PMID- 12512795
TI  - Acupuncture used in the management of pain due to arthropathy in a patient with
      haemophilia.
AB  - A case report is presented of a haemophilia patient, with pains due to
      arthropathy, being successfully treated with acupuncture. Acupuncture may have
      something to offer this type of patient in terms of pain management and reduction
      of strong analgesics. Treatment should be performed only by practitioners with
      special training in acupuncture, and close co-operation with a haemophilia clinic
      is necessary.

PMID- 12512796
TI  - Relevant animal model of human lymphoblastic leukaemia/lymphoma--spontaneous T
      cell lymphomas in an inbred Sprague-Dawley rat strain (SD/Cub).
AB  - More than a decade of experimental work in an inbred subline of Sprague-Dawley
      rats having high incidence of spontaneous T-cell lymphoma/leukaemia is reviewed.
      Longitudinal follow-up of biological characteristics (growth, survival,
      haematology) of both multiple cases of primary disease and s.c. passaged
      lymphomas as well as comparative immunophenotypic and karyotypic studies are
      concluded. In these T-cell lymphomas (mostly CD4 positive), arising on the same
      genetic background of the inbred SD strain, the aberrations involving chromosome
      11 have been recognized as a typical non-random cytogenetic marker. This unique
      rat model of lymphoblastic lymphomas/leukaemias, relevant to human pathology,
      seems to be very suitable for testing different anticancer therapeutic
      strategies, as it is documented by results of a number of various protocols
      conducted in our laboratory.

PMID- 12512797
TI  - Analysis of transcription of plant 7SL RNA gene variants in HeLa in vitro
      transcription system.
AB  - We have performed an analysis of transcription of hop 7SL RNA genes in
      heterologous human extract from HeLa cells. Several variants of the Hl7SL-1 gene
      with a truncated or mutated 5' non-transcribed part revealed a crucial importance
      of TATA box for transcription. The USE element was found important but
      dispensable for transcription. Transcription of mutants in the A-like box and
      experiments with hop 7SL RNA pseudogenes E44 and G32 revealed the importance of
      internal elements. The A-like box and possibly CG doublet at position +15/+16
      described by Bredow et al. (1990a) are according to our results indispensable for
      in vitro transcription of plant 7SL RNA genes in human extract.

PMID- 12512798
TI  - Role of a capacitation-related protein on some sperm functional parameters.
AB  - In previous studies a series of Mabs against boar capacitated sperm have been
      produced. One of these Mabs--4B12--was found to recognize a surface membrane
      associated protein located in the acrosome portion of the spermatozoa that became
      accessible to antibody after capacitation. In biological experiments it was shown
      that Mab 4B12 significantly inhibited boar sperm-porcine ZP binding. In attempts
      to investigate the mechanisms by which Mab 4B12 affected sperm-ZP binding, the
      role of the cognate protein on some functional parameters such as sperm motility
      and ability of the capacitated spermatozoa to undergo AR was studied.
      Experimental models of premature AR and AR physiologically induced with ZP were
      applied to study the effect of Mab 4B12 on boar sperm AR using PSA staining to
      estimate the acrosome-reacted state of spermatozoa. Sperm motility
      characteristics were determined by the time-exposure photokinesigraphic method.
      The results obtained in the present study, together with previously established
      inhibition of sperm-ZP binding by Mab 4B12, documented the participation of the
      4B12 protein in primary sperm-ZP binding. The protein is not connected with sperm
      motility and secondary sperm-ZP binding.

PMID- 12512799
TI  - Rosiglitazone improves insulin resistance, lipid profile and promotes adiposity
      in a genetic model of metabolic syndrome X.
AB  - RSG is a member of the TZD group of drugs widely used in treatment of type 2
      diabetes. The underlying mechanism of TZD action in insulin-sensitive tissues is
      not fully understood. In this study we show that 14-day RSG administration in a
      new rodent model of metabolic syndrome X, polydactylous rat strain (PD/Cub),
      substantially improves its lipid profile (serum TGs 4.20 +/- 0.23 vs 2.34 +/-
      0.14 mmol/l, P < 0.0001; FFA 0.46 +/- 0.05 vs 0.33 +/- 0.02 mmol/l, P = 0.017),
      diminishes the liver TG depots (15.76 +/- 0.60 vs 8.44 +/- 0.55 micromol/g, P <
      0.0001), serum insulin concentrations (1.10 +/- 0.08 vs 0.63 +/- 0.02 nmol/l, P <
      0.0001) and promotes visceral adiposity (adiposity index 1.28 +/- 0.03 vs 1.85 +/
      0.07, P < 0.0001). No changes were observed in serum or liver concentrations of
      cholesterol. Concomitantly, both basal and insulin-stimulated glycogen synthesis
      in red-fibre type muscle (m. soleus) was enhanced, as well as glucose uptake into
      adipose tissue. However, glucose oxidation in soleus (basal and insulin
      stimulated) remained unchanged. In consent with previously published data we
      suggest the current pharmacogenetic study as a further proof of substantial
      influence of genetic background on the physiological outcome of TZD therapy.

PMID- 12512800
TI  - Freezing and thawing of murine bone marrow-derived dendritic cells does not alter
      their immunophenotype and antigen presentation characteristics.
AB  - The aim of this paper was to assess whether the BMDC after freezing and thawing
      are capable to retain the immunophenotype and antigen-presenting capacity. BMDC
      were generated from bone marrow precursor cells as described previously by
      culturing the cells in medium containing GM-CSF and IL-4. Afterwards, the cells
      were harvested, counted and used for phenotyping and priming of syngeneic spleen
      cells. For cryopreservation, the BMDC were frozen in the presence of 10% of
      dimethylsulphoxide (DMSO) and 90% foetal calf serum. Forty to fifty percent of
      both samples, frozen/thawed as well as fresh BMDC, exhibited characteristic DC
      morphology, and the DC obtained from the frozen/thawed samples expressed a
      similar level of MHC class I-, MHC class II-, CD80-, CD86-, CD11c-, CD11b-, CD54-
      and CD205-molecule as fresh DC. To examine the in vitro priming effect of
      cryopreserved BMDC on syngeneic non-adherent murine C57BL/6 (B6) spleen cells,
      the BMDC were thawed, pulsed with the lysate prepared from HPV 16-associated
      tumour MK16 and used for 3H-thymidine assay. The findings of the experiments
      indicate that fresh as well as cryopreserved murine BMDC preparations pulsed with
      tumour lysate were efficient to prime the mitogenic activity of syngeneic non
      adherent splenocytes. Taken together, the results suggest that frozen/thawed BMDC
      are morphologically, phenotypically and functionally comparable with fresh BMDC
      and can be used for construction of dendritic cell-based tumour vaccines.

PMID- 12512801
TI  - DicodonUse: the programme for dicodon bias visualization in prokaryotes.
AB  - The DicodonUse programme is aimed at a fast and simple assessment of genes
      present in prokaryotic nucleotide sequences. It identifies open reading frames
      that are not genes, and it distinguishes the genes that inherently belong to the
      genome in question from the genes that were inserted into the genome in the
      course of evolution. The programme is based on frequencies of dicodons used by
      the organism.

PMID- 12512802
TI  - Recognition of antigenic components of Fasciola gigantica and their use in
      immunodiagnosis.
AB  - Antigenicity of the tegumental extract, excretory-secretory products and the
      whole somatic extract of Fasciola gigantica were evaluated to detect the most
      sensitive and specific antigen out of them that could be used as an immuno
      diagnostic tool. Scanning electron microscopic study was carried out to have a
      full picture about the tegumental structure. The immunohistochemical staining
      technique was done using the indirect immunoperoxidase method on F. gigantica
      sections before and after removal of the tegument to recognize the most antigenic
      parts by using patients sera. Counter immunoelectrophoresis was carried out by
      using sera from patients with fascioliasis (positive control), patients with
      schistosomiasis and healthy individuals (control group). In addition, antibody
      response against the three types of antigens was detected as ELISA absorbance
      readings. The results revealed that antigens of F. gigantica that cause antibody
      formation in hosts are those generated and released mainly from the tegument.
      They were the most sensitive and specific.

PMID- 12512803
TI  - Effect of the iron chelator deferoxamine on Trichomonas vaginalis in vitro.
AB  - The effect of 10 microMol, 15 microMol, 30 microMol, and 60 microMol
      concentrations of deferoxamine (DFO), a clinically approved iron chelator, was
      determined on viability and multiplication of Trichomonas vaginalis grown in TYM
      axenic culture medium at 24 hours interval. DFO killed all T. vaginalis isolates
      with a minimum lethal concentration of 30 microMol after 48 hours culture
      incubation with the drug. A potent and persistent inhibitory effect of DFO on the
      parasite viability and multiplication was recorded throughout the study till its
      end, in a drug concentration and time exposure-dependent manner. Furthermore, the
      present work studied the proteinase activity of T. vaginalis grown for 48 hours
      in DFO inoculated TYM medium, and recorded a significant decrease by all drug
      concentrations applied in the work. Different possible mechanisms of action of
      DFO against T. vaginalis and its possible use for treatment of trichomoniasis are
      discussed.

PMID- 12512804
TI  - The ultrastructural study of microgametogenesis of Eimeria scinci Phisalix 1923
      (Apicomplexa: Eimeriidae) infecting the sandfish lizard, Scincus mitranus
      Anderson 1871 in Saudi Arabia.
AB  - The ultrastructure of microgametogenesis of Eimeria scinci Phisalix 1923 was
      described for the first time in the gall bladder epithelium of experimentally
      infected sandfish lizards, Scincus milranus Anderson 1871 from Al-Baha region in
      Saudi Arabia. Recorded sequence of events started as sexually differentiated
      second generation merozoites transformed into microgamonts, where most of the
      apicomplexan organelles have been disappeared gradually. Microgamonts were
      recognizable by the presence of peripherally arranged nuclei and the presence of
      one or two centrioles between each nucleus and the limiting membrane of the
      gamont. Early microgamonts were surrounded by a very narrow parasitophorous
      vacuoles, which widened during development and contained a few intravacuolar
      folds and tubules. Differentiation of microgametes began by elevations of the
      limiting membrane appeared above the centrioles and the segregation of nuclear
      content into a dense osmiophilic portion and an electron-pale one. A gradual
      protrusion of the dense portion of the nucleus and the developing flagella into
      the parasitophorous vacuole was proceeded. Fully developed microgametes become
      detached and occupied the parasitophorous vacuole along with the residual body of
      the mother microgamont. Each microgamete had at least two flagella; an anterior
      perforatorium; a dense elongate nucleus and an anteriorly located tubular
      mitochondrion. The (9x2+2) pattern of flagella was detected in transverse
      sections.

PMID- 12512805
TI  - A preliminary pilot survey on head lice, pediculosis in Sharkia Governorate and
      treatment of lice with natural plant extracts.
AB  - Twelve different representative areas in Sharkia Governorate were surveyed for
      head lice, Pediculus humanus capitis. The pre-valence was investigated among 120
      houses containing 2,448 individual, with different age, sex and socioeconomic
      status. Examination was done by naked eye aided with hand-lens. A total of 137
      individuals were infested. Infestation rates were higher in the rural areas with
      low socioeconomic levels, concrete houses with over-crowded family members.
      Children had significantly higher infestation rates than adults. Males had lower
      infestation rates than females. However, the hair length and permanent hair
      washing were the factors accounted for both age and sex difference in prevalence
      of pediculosis. Head lice infestations were found all over the year, but
      increased in summer and spring. One hundred infested patients (90 females and 10
      males) with different aged and hair length were treated with tour mixed cream
      from plants Lawsonia alba L. (Henna). Trigonella faemum-gracanum (Fenugreek),
      Hibiscus cannabinus (Hibiscus) and Artemisia cina (Wormseed). The head lice
      completely disappeared within a week among those patients treated by henna mixed
      with aqueous extract of sheah (100%) or mixed with helba (75%) or with karkada
      (50%).

PMID- 12512806
TI  - The red fox, Vulpes v. aegyptiaca, a new host of leishmania major in Sinai
      Peninsula.
AB  - A leishmanial isolate was obtained from the ear of one red fox or Nile fox
      (Vulpes v. aegyptiaca) out of eight from North Sinai Governorate. The isolate was
      typed by the enzymatic variant profiles of the four enzymes, GPI, G6PD. 6PGD and
      PGM against the three Old World reference strains, L. major, L. tropica and L.
      donovani and proved to be Leishmania major. This is the second time that L. major
      has been shown to occur in canine hosts. The list of the mammalian hosts of L.
      major was reviewed and discussed.

PMID- 12512807
TI  - Bacterial-parasite interaction between Salmonella and each of Fasciola gigantica
      and Trichinella spiralis.
AB  - The possibility of bacterial-parasite interaction between Salmonella typhimurium
      and the surface of each of Fasciola gigantica metacercariae and Trichinella
      spiralis larvae was investigated in vitro. Two studies were carried out. In the
      first, S. typhimurium were incubated in vitro with the metacercariae of F.
      gigantica. In the second, S. typhimurium was incubated with larvae of T.
      spiralis. The interactions of S. typhimurium with each of F. gigantica
      metacercariae and T. spiralis larvae were studied by scanning electron microscope
      (SEM). In the first study, numerous bacilli were found adhered to the
      metacercariae surface. In the second study, no S. typhimurium was observed on the
      wall of T. spiralis larvae. The results indicated that only F. gigantica
      metacercariae act as a carrier for S. typhimurium with the possibility of
      occurrence of mixed infections with both organisms. So, both fascioliasis and
      salmonellosis must be treated concomitantly.

PMID- 12512808
TI  - Antibody profile, interferon-gamma and nutritional status in cryptosporidial
      infection among school children.
AB  - Cryptosporidium parvum is more common in children than in adults. The host
      responses that induce protective immunity against Cryptosporidium is poorly
      understood. The present work studied the antibody profile, interferon gamma (IFN
      gamma) serum level and nutritional status among infected school children, aged
      eleven years in a rural school in Abis 8 village. Fecal examination showed
      nineteen cases only infected with Cryptosporidium and ten children free from
      parasites (controls). The IgA, IgG and IgM serum levels in infected cases were
      within normal level, without significant differences as compared to controls. The
      IgE serum level was significantly high in infected children. The cytokine IFN
      gamma was significantly lower in the infected cases as compared to controls.
      Malnutrition was diagnostic among infected children. It was concluded that
      malnutrition is the important finding related to Cryptosporidium infection.
      Malnutrition decreased IFN-gamma the recognized factor in protection from
      infection and elevated serum IgE level.

PMID- 12512809
TI  - A woman and her son with abnormal complicated anthrponotic cutaneous
      leishmaniasis.
AB  - Anthroponotic cutaneous leishmaniasis (ACL.) is known to cause single, self
      healing and uncomplicated lesion mainly on the face. This paper presents a son
      and his mother with positive leishmaniasis IHAT (1/128 and 1/1924 respectively).
      The two isolates by enzymatic electrophoresis characterization proved to be
      Leishmania tropica that causes ACL. The son had two large ulcerative ACL on his
      left hand. The mother had a large ulceration and progressive erosion of the soft
      tissue (the right cheek and right eye) and the cartilage of the nose disfiguring
      and debilitating her face. The histpathological examination of the biopsy
      material obtained from the mother but not the material from her son, showed
      typical pathological picture of the basal cell carcinoma. No doubt, there are
      progressive changes in the pathogenesis of L. tropica and that it is one of the
      predisposing factor of the skin cell carcinoma.

PMID- 12512810
TI  - Biological studies on the snail intermediate hosts of schistosomiasis with a
      special emphasis on using larval echinostomes as biocontrol agent against larval
      schistosomes and snails.
AB  - The present investigation deals with the infectivity of the two snail
      intermediate hosts of schistosomiasis, Biomphalaria alexandrina and Bulinus
      truncatus collected from nine drains in Sharkia Governorate, Egypt. The rate of
      infection among the snails was general low being 0% in many drains. Regarding B.
      alexandrina, the rate of infection ranged from 4-16%, and in B. truncatus ranged
      from 4-8%. Infection with larval echinostomes was dominant over larval
      schistosomes in the two snail vectors. The distribution of larval schistosomes
      was restricted to the hepatopancreas of the two snail vectors, while larval
      echinostomes were distributed in head, foot, kidney, haemocoelic cavity,
      hepatopancreas...etc. The predation of larval schistosomes by larval echinostomes
      and the severe histopathological effects induced by larval ecbinostomes strongly
      enhances using them as biocontrol agent. The physico-chemical parameters and
      pollution condition in the drains seem to have no effect on the process of snails
      infectivity. It is concluded that larval echinostomes can resist the polluting
      conditions in the drain. The two snail vectors exhibit very minimal or rare host
      response against larval echinostomes. Probably, the toxicants and pollutants in
      the drain may act as stressor that makes the snails much more susceptible to
      infection by larval trematodes.

PMID- 12512811
TI  - Pathogenicity of two entomopathogenic hyphomycetes, Beauveria bassiana and
      Metarhizium anisopliae, to the housefly Musca domestica L.
AB  - The pathogenicity of three isolates of Metarhizium anisopliae and two isolates
      Beauveria bassiana originating from different insect species and localities was
      tested against housefly larvae. Only one isolate of M. anisopliae (Ma23) and the
      two isolates of B. bassiana (Bb2, Bb108) significantly (P<0.05) reduced the
      percentage of emerging adults. At the highest tested concentration 10(7)
      spores/ml. the reduction in the percentage of adult emergence was 93.8%. 61.3%
      and 49% for Bb2. Ma23 and Bb108. respectively. Based on the IC50 values Bb2 was
      the most virulent isolate followed by Ma23 and Bb108, (1.13. 1.7 and 4 x 10(6).
      respectively). The ability of adult flies to pick up conidiospores from
      contaminated media as well as the possibility of isolate recycling through
      cadavers of fungus-killed adults were also investigated. Adults were able to pick
      up conidiospores from the contaminated media. All contaminated adult cadavers
      subsequently sporulated when placed under high relative humidity conditions. When
      adult flies were exposed to mycotised cadavers 12. 75 and 76% of the adults
      exposed to Bb2, Ma23 and Bb108, respectively sporulated under high relative
      humidity conditions.

PMID- 12512812
TI  - Eucalyptus globulus (camphor oil) in the treatment of human demodicidosis.
AB  - Demodex folliculorum (Follicular or Demodicid mite) is a zoonotic obligatory
      parasite with clinical manifestations range from normal infestation to
      complicated ones. Treatment of human facial demodicidosis with freshly prepared
      camphor oil with or without glycerol dilutions gave complete cure with
      concentrations of 100%, 75%. and 50%. Incomplete cure but marked drop in
      infestation density was achieved with diluted camphor oil at concentrations of 25
      20%. Camphor oil application proved to be safe with no side effects.

PMID- 12512813
TI  - Some field and laboratory studies on Rattus rattus subspecies and Rattus
      norvegicus in two Egyptian governorates of different ecological characters.
AB  - Both Damietta and Qualyobia governorates were examined for the seasonal
      activities of Rattus species and subspecies and their natural infection with
      Trypanosoma lewisi. The common domestic rodents identified were Rattus r.
      alexandrinus, R. r. frugivorus and Rattus norvegicus. They were common all the
      year round except in winter for R. norvegicus in Damietta. Gravid females of the
      three rodent species, were identified in Damietta in summer, in addition to
      Autumn for R. norvegicus only. In Qualyobia, gravid females of the three rodent
      species, were identified in spring, in addition to autumn for R. norvegicus only.
      The heaviest rodent in weight, was R. norvegicus, in summer (Damietta), and in
      spring (Qualyobia). The three rodent species were naturally infected with T.
      lewisi. The whole results were discussed on the light of the work done before,
      with reference to the feasible time to apply rodenticides.

PMID- 12512814
TI  - Upgrading of Kato-Katz technique for diagnosis of S. mansoni infection in rural
      Egypt.
AB  - Processing of the same stool samples was done using standard Kato-Katz (KK)
      technique with 41.7 mg of stools and one of the three modifications. These
      included KK technique using a higher concentration of glycerin (one and quarter,
      usual one) for preparation, or another stain (negrosin-eosin), with a specified
      formula, instead of the standard malachite green, or processing a smaller volume
      of stools (20mg). The results showed that, using cumulative infection rate from
      the two comparable tests as the reference, KK with higher concentration of
      glycerin was more sensitive than standard KK (sensitivities 77.6% and 61.2%.
      respectively). Using negrosin-eosin stain showed higher sensitivity (75.0%) in
      relation to standard KK technique (70.8%). Kato-Katz with higher concentration of
      glycerin showed the same sensitivity as KK with negrosin-eosin stain (85.7%) in
      relation to others. All comparisons showed statistically insignificant
      differences ((P>0.5). Using 20 mg of stools showed very low sensitivity in
      relation to standard KK technique (57.9% & 100.0% respectively). The statistical
      difference was highly significant. All specificities were 100%. Other screening
      indices showed the same trend of sensitivities. Degree of microscope clarity was
      optimal with higher concentration of glycerin. Negrosin-eosin showed better
      visualization of ova than the standard KK. All modifications took only an hour
      after processing to be examined. KK technique used with any of these
      modifications, is simple, inexpensive. use of either a higher concentration of
      glycerin or negrosin-eosin stain and recommended for both field studies and
      primary health care settings.

PMID- 12512815
TI  - Molluscicidal effect of fungicide, herbicide and plant extract on some biological
      and physiological parameters of Biomphalaria alexandrina.
AB  - In was found that the exposure of B. alexandrina to LC25 of fungicide
      (Isoprothiolane), herbicide (Anilofos) and plant extract (Euphorbia lactea) led
      to highly significantly elevated in the number of abnormal egg masses laid by
      treated snails in comparison with the control ones. The LC25 caused reduction in
      infection rate of B. alexandrina. It caused reduction in number of cercariae per
      snail during the patent period and reduction in the period of cercarial shedding.
      The results obtained showed that adenosine triphosphatase (ATPase) activity of
      tissue of snails was significantly increased in response to tested substances.
      The activity level of lactate dehydrogenase (LDH). pyruvate kinase (PK) and
      phosphoenolpyruvate carboxy kinase (PEPCK) was significantly reduced in response
      to treatment. This reduction does not reflect on both D. lactate and pyruvate
      concentrations.

PMID- 12512816
TI  - Effect of two herbicides on some biological and biochemical parameters of
      Biomphalaria alexandrina.
AB  - The herbicides, Butachlor and Fluazifop-p-butyl were evaluated against B.
      alexandrina and their infection with S. mansoni, as well as against the miracidia
      and cercariae. The tested herbicides reduced the survival and infection rates of
      B. alexandrina by 28% and 35.71% for Butachlor and 50% and 64% for Fluazifop-p
      butyl, respectively. These herbicides significantly reduced the production and
      duration of cercairal shedding per infected snails. The mortality rates of
      miracidia and cercariae were elevated gradually by increasing the sub-lethal
      concentrations of herbicides being 63% and 62%, respectively, after 6 hours of
      exposure to 6.5 ppm of Butachlor. The protein, glycogen and lipid contents in the
      snail Soft tissues were significantly reduced. There was a significant elevation
      in the levels of acid and alkaline phosphatases in haemolymph of snails exposed
      to Butachlor, 0.05 and 0.48 u/mg protein, respectively.

PMID- 12512817
TI  - Bancroftian filariasis: clinical parasitologic and serologic evaluation after 4
      years applying two antifilarial regimens.
AB  - In August 1 997, 124 individuals out ot 1,110 were selected as being seropositive
      for circulating filarial antigen OG4C3 (CFA). Ten healthy children proven
      negative for CFA were used as controls. The patients were classified into: G1 28
      patients; 20 asymptomatic microfilaraemic and 8 symptomatic amicrofilaraemic
      (AMF), G2 80 patients, 22 asymptomatic MF, 48 asymptomatic AMF and 10 symptomatic
      AMF and G3 16 asymptomatic AMF. G1 was treated by single annual dose of diethyl
      carbamazine (DEC) (6mg/kg), G2 by single annual dose of albendazole 400 mg and
      DEC 6mg/kg and G3 untreated. Four years later (2001), patients Were re-evaluated.
      Microfilaraemia prevalence in MF patients was lowered to 20% (G1) and 9.1% (G2).
      Antigenaemia prevalence was lowered to 46.4%, 17.5% and 87.5% in the three groups
      respectively. The disease became manifested among the asymptomatic in 5% (G1) and
      10% (G2), but 25% (G3). The four years lowered the prevalence of microfilaraemia,
      but it was not sufficient for its elimination from the blood. So, a program to
      eliminate filariasis should be extended beyond this period to achieve no
      transmission and minimizes newly cases.

PMID- 12512818
TI  - Enzymatic changes and cytotoxic effects of Metarhizium anisopliae fungal extracts
      on the Egyptian cotton leaf worm Spodoptera littoralis (SL 96) cell line.
AB  - The extra-and intra-cellular extracts of two Metarhizium anisopliae isolates:
      Ma23 and MR3, were introduced to a cell line of Spodoptera littoralis. The cell
      line (Sl96) was established in the Entomovirology centre from S. littoralis
      ovaries. MR3 extracellular fluid-treated culture had an increase in the Acid
      phosphatase (AcP) level as compared either to the untreated cell line or to the
      fungal extract alone. Moreover, the enzymatic tests showed that alpha and beta
      glucosidases have been detected only after the treatment with extracellular fluid
      of MR3. The elevation of AcP level that appeared after the treatment of MR3
      coincided with a conspicuous decrease of about one third of the initial number
      (96 x 10(3)) of the Sl96 cell. vacuolization and lysis of some cells. Deformation
      of the cells and shrinkage of cell membrane have been observed in the case of
      Ma23 treatments. Crystal formation was restricted to the treatment of MR3
      extracellular extract. The results are discussed in the light of the possibility
      that the cytotoxic effects and enzymatic changes are attributed to the virulence
      of the fungal isolates.

PMID- 12512819
TI  - Sarcosaprophagous flies in Suez province, Egypt. I--Seasonal distribution and sex
      ratio.
AB  - Seasonal field studies on 4 bait traps (Fish, Bovine-lung, Grapes and Molasses)
      were conducted in El-Arbaeen fish-market, El-Arbaeen district, Suez governorate
      Egypt in 1999 and 2000 to describe the pattern and sex-ratio of sarcosaprophagous
      flies. The presence of sarcosaprophagous flies (Calliphoridae, Muscidae and
      Sarcophagidae) revealed that Chrysomya megacephala (Fabricius), Lucilia cuprina
      (Wiedemann) and Musca domestica (Linnaeus) were the most dominant flies. Almost
      equal number of male and female flies of C. megacephala, L. cuprina and M.
      domestica trapped on baits of grapes and molasses, possibly represent real
      proportion of male and female population of these flies. The number of female
      flies recorded on fish and bovine-lung baits was significantly higher than those
      recorded on grapes and molasses. As row fish and bovine-lung are important
      breeding media for flies, they may have attracted a larger number of female flies
      for ovary maturation and oviposition.

PMID- 12512820
TI  - Studies on helminthes infecting some local fishes in Kuwait.
AB  - A total of 37 silver pomfret (Pampus argenteus), 67 greasy grouper (Epinephelus
      tauvina), 52 red snapper (Lutjanus coccineus), and 56 silver croaker (Otolithes
      argenteus) were examined during the period form October 2001 to September 2002
      for the purpose of studying the helminth parasites including Monogenea, Digenea,
      Cestoda, Nematoda and Acanthocephala. All examined fishes were free from any
      species of Cestoda, Trematoda or Acanthocephala. Only P. argenteus and L.
      coccineus were infected with Nematoda. The relationships between the helminthic
      infection rates and the environmental factors were studied.

PMID- 12512821
TI  - Anthelminthic efficacy of traditional herbs on Ascaris lumbricoides.
AB  - The ascaricidal efficacy of six commonly used traditional herbs. Artemesia
      santonica, Inula helenium, Cassia abutnsifolla, Albizzia lebbek, Acacia
      auriculoformis and oil of Apium graveolens, was tested in vitro against the eggs
      and larvae of Ascaris lumbricoides. Aqueous extracts of 1% Artemesia and 5% of
      Albizzia and Inula were effective in killing both the infective larvae ill less
      than 40 days and eggs in 20 days. The results showed that Artemesia, Albizzia and
      to less extent Inula were promising antihelmintics against Ascaris lumbricoides.
      Extracts of the other tested herbs were less or no value.

PMID- 12512822
TI  - Ant allergy in Benha District Qualyobia Governorate, Egypt.
AB  - Individuals from the suburb of Benha City and some adjacent villages were
      presented with various degrees of skin allergy. In addition, chiildren who spend
      the night (sleep) on the floor suffered generalized lymphadenopathy, with or
      without fever. The patients were successfully treated with carbolic acid (1:25).
      Besides, oral anti-histamine (H1) and systemic antibiotics were indicated in the
      complicated cases. In the concrete houses of the patients, a huge number of the
      large ants (mainly Catagliphus bicolar) were found moving here and there,
      particularly in animal house included indoors. Spreading or burning dried leaves
      of camphor tree proved to an effective repellent for the ants. Discussion focused
      on the medical importance of ants.

PMID- 12512823
TI  - Vascular endothelial growth factor level in chronic liver diseases.
AB  - Ninety individuals (76 males and 14 females) were classified into four groups. G1
      (Control) included 20 healthy individuals. G2 (Chronic hepatitis) included 20
      patients, G3 (Liver cirrhosis group) included 30 patients, and G4 (HCC) included
      20 patients with HCC. All groups were subjected to clinical examination,
      abdominal ultrasonography, complete blood picture, HCV antibodies, HBs Ag, and
      function tests (total and direct bilirubin, total plasma proteins and albumin,
      prothrombin time and concentration, and liver enzymes AST, ALT and ALP). Patients
      of G3 & 4 were classified according to Child-Pugh classification into A. B and C.
      Upper endoscopic examination was done for 36/50 patients with chronic hepatitis
      or HCC. Circulating VEGF levels were determined by ELISA. There was a
      statistically high significant levels of circulating VEGF in G1, 2 & 3 than in
      the controls. A statistically significant higher level of circulating VEGF in G4
      than in G3 & G4, and a statistically negative significant between VEGF levels and
      platelet count in G2. No significant correlation between VEGF and the grade of
      esophageal varices in G3 & G4. and no significant correlation between VEGF and
      upper GIT bleeding or spider naevi (vascular skin changes) in G2. A statistically
      significant was in correlation between VEGF and degree of hepatic dysfunction.

PMID- 12512824
TI  - A scanning electron microscopy study of Musca domestica larvae.
AB  - The micro-morphology of the house fly, Musca domestica larvae was studied by
      scanning electron microscopy (SEM). The ultra-structure of the mouth-hooks, oral
      ridges, spinulation of body segments and posterior spiracles, was photographed
      and described.

PMID- 12512825
TI  - IgG isotypes in schistosomiasis patients before and after praziquantel.
AB  - This work evaluated circulating anti-SWAP IgG1 and IgG4 in patients with active
      S. mansoni infection before and after PZQ and its correlation to clinical,
      laboratory and sonographic data. The main complaints was abdominal discomfort,
      pain, tensmus and bleeding per rectum, which progressive decreased after PZQ. The
      anti-SWAP IgGI and IgG4 were significantly higher in patients than controls. A
      progressive significant decrease in the level of circulating anti-SWAP IgG1 after
      treatment, a decrease of IgG4 three months after treatment and a decrease in the
      egg count after therapy. But, no significant difference in IgG1 or IgG4 was
      noticed between male and female patients before and after treatment. No
      significant difference in IgGI or IgG4 in patients having GIT manifestation and
      organomegalic patients and/or asymptomatic patient. No significant difference in
      lgG1 or IgG4 between patients with grade (o), graele (I) and grade (II)
      periportal fibrosis. The sensitivity of ELISA IgGI was 73.3% and specificity was
      80% while ELISA IgG4 was 80%. Enlarged liver and/or spleen, periportal fibrosis,
      and dilated P.V detected by ultrasonography were more among patients than
      controls. There was no significant difference in hematological parameters and
      liver function tests between patients and control groups. So, ELISA is sensitive
      and specific for IgG1 and IgG4. Anti-SWAP IgG1 and IgG4 is useful means in
      diagnosis and cure, as well as significant reduction of anti-SWAP IgG1 and IgG4
      after treatment. Anti-SWAP IgG1 and IgG4 are parameter for evaluating cure.
      Follow up of anti-schistosomal IgG1 and IgG4 is useful for assessment of
      treatment

PMID- 12512826
TI  - The pattern of cryptosporidiosis in experimentally immune deficient albino rats.
AB  - Thirty clean laboratory bred male albino rats were divided into two groups. G1,
      twenty rats received corticosteroids (SC. injection of 1.5 mg dexamethasone,
      twice per week) for eight weeks for immuno-suppression, while G2, ten rats served
      as controls. Both groups were separately caged under controlled laboratory
      observation and given normal diet. After the 8th week, both groups were allowed
      to acquire Cryptosporidium parvum infection by feeding on infective source.
      Another week more, all animals were subjected to stool examination and were then
      sacrificed. Rats of G1 showed oocysts in 13/16, but none in rats of G2. Scrapping
      of the intestinal mucosa from both rats of G1 and G2 were prepared for
      microscopic examination, after stained in modified Kinyoun acid-fast (light
      microscope), and Auramine (fluorescent microscope). Cryptosporidium oocysts were
      demonstrated in 13/16 (81.3%) of G1 and 3/10 (30%) of G2. So, cryptosporidiosis
      as an opportunistic parasite threats in immune deficiency.

PMID- 12512827
TI  - Identification of some monogenetic treamatodes from some Arabian Gulf fish in
      Saudi Arabia.
AB  - Examination of 90 Epinephelus chlorostigma and 50 Lethrinus nebulosus reaveled
      that 99% of the former harboured monogenea belonging to two species. (1)
      Megalocotyloides epinepheli Bychowsky and Nagibina, 1976 (Encolyllabe), 1-6 worm
      per fish, from buccal cavity, attached to lower pharyngeal plate between teeth.
      (2) Pseudorhabdosynochus epinepheli Yamaguti, 1938 (Diplectanum), over 100 worms
      per fish from the gills. On the other hand 4% of L. nebulosus harboured another
      two species of monogenea (1). Polylabris angifer Hussey, 1986, 1-2 worms per fish
      from the gills. (2). Polylabris sp. only one worm from the gills. As far as it
      can be concluded. this is a new locality and new hosts of the four species of
      worms.

PMID- 12512828
TI  - Efficacy of azithromycin, praziquantel and mirazid in treatment of
      cryptosporidiosis in school children.
AB  - The study was conducted at a primary school in Abis 8 village. 88 children aged
      eleven years consented to participate in the present study. After fecal
      examination, 43 (48.8%) cases were found infected with Cryptosporidium. The mean
      oocysts number per high power field (HPF) ranged from (1.6-48 oocysts/HPF).
      Azitbromycin, praziquantel (PZQ) and mirazid were given to 13, 16 and 14 infected
      children respectively. Three weeks after treatment, azithromycin and praziquantel
      gave cure rates of 91% and 56.2% respectively with a percent reduction of oocysts
      in stools of 99% for azithromycin and 71.5% for PZQ. Mirazid was not effective.
      All the three drugs were well tolerated. It was concluded that azithromycin is
      highly effective in the treatment of children with cryptosporidiosis: PZQ
      decreases the infection rate and intensity.

PMID- 12512829
TI  - Low avidity IgG antibodies in diagnosis of recent human schistosomiasis.
AB  - One hundred thirty school children from a schistosomiasis endemic area in Sharkia
      Governorate, were selected on parasitological findings. Seventy persons were
      negative on the first screen and turned positive after 3 months of the screening
      (recently infected). Stool examination, ELISA (IgG & IgM), low avid IgG, and
      circulating antigens were performed for all patients and controls. ELISA detected
      IgM in all cases. IgG and circulating antigens in 90% of schistosomiasis
      patients. Low avidity IgG were detected in 85.71% of recent cases. The
      specificity of ELISA appeared to be >99%. The IgM/IgG ratio was >1 in patients
      with recent infection. The percentage of fall of O.D. readings of IgG after
      addition of 6 molar urea was high among cases with recent infection. Low avid lgG
      appears to be good and valuable in diagnosis of recent schistosomiasis in man.

PMID- 12512830
TI  - Effect of schistosoma mansoni egg deposition on multiple low doses streptozotocin
      induced insulin dependent diabetes.
AB  - To explore the role of Schistosoma mansoni infection in the prevention of
      autoimmune mediated insulin dependant diabetes mellitus, we examined the effects
      of multiple low doses of the pancreatic islets beta cell toxin, streptozotocin
      (STZ) 40mg/kg body weight i.p., given 8 weeks post infection, period of S.
      mansoni egg deposition, on S. mansoni infected C57BL/6J mice, in comparison to
      non-infected STZ given group. Mice treated with STZ (G III) became gradually
      hyperglycemic reaching highest level on days 17 post STZ with mean blood glucose
      level of 334.9 +/- 14.9 vs 130.3 +/- 9.2 mg/dl in control group (G IV). S.
      mansoni infection (G II) significantly reduced the elevation in blood glucose
      levels from days 7 post STZ onwards reaching 224mg/dl +/- 12.7 on days 17 (P <
      .0.001). Morphologic examination of pancreas on day 21 post STZ, revealed that
      the non-infected STZ (G III) given mice had significantly smaller mean islets
      area (5,060.51 mu2 +/- 1,567.28) and significantly fewer mean number of beta
      cells/islets (76.23 +/- 19.18) than the infected STZ given group (G II) which had
      mean islets area (9,305. 3l mu2 +/- 3,277.59) and 116.75 +/- 27.27 beta
      cells/islets. Pancreatic tissue revealed also focal degeneration in the cells of
      islets of Langrhans in the non-infected STZ given mice (G III), in comparison, to
      the infected STZ given group (G II). which had much less evident cells
      degeneration. These findings revealed that S. mansoni egg deposition which leads
      to a shift from Th1 (IFN-gamma mainly) to Th2 (IL4, IL5, IL10 and TGF-beta
      cytokine profiles causes down-regulation of the Th1 cell mediated autoimmune
      insulin dependant diabetes mellitus (IDDM). On the other hand, S. mansoni eggs
      excretions were significantly lower in the infected STZ given group (G II) than
      the infected group (G I). This finding may be the result of impaired maturation
      of egg in diabetic mice. It is concluded that the modulation of immune response
      in S. mansoni infected mice with S. mansoni egg deposition, can suppress the
      autoimmune type 1 insulin dependant diabetes mellitus induced by multiple low
      doses streptozotocin.

PMID- 12512831
TI  - Hepatitis C virus and Culex pipiens complex.

PMID- 12512832
TI  - Monoclonal antibody therapy for B-cell lymphoma.
AB  - Treatment strategies and outcomes for patients with non-Hodgkin's lymphoma (NHL)
      are undergoing rapid and important evolution. We have recently witnessed the
      advent of novel targeted therapies, such as gene therapies, active
      immunotherapies, antisense therapies, new small molecules and biologicals, and
      monoclonal antibodies (MoAbs). The first MoAb approved for the treatment of
      cancer, rituximab, was approved in 1997 and has been rapidly incorporated into
      treatment regimens for NHL. In a randomized trial in combination with CHOP
      chemotherapy (cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone),
      rituximab showed superiority to CHOP for patients with diffuse large cell NHL
      (DLCL).The rituximab + CHOP combination has become the gold standard for
      frontline therapy for DLCL and has shown significant activity in the management
      of follicular NHL. In February 2002, the first radioimmunotherapeutic agent for
      the treatment of cancer, ibritumomab tiuxetan (Zevalin), was approved.
      Ibritumomab tiuxetan, an yttrium-labeled antibody used in conjunction with
      rituximab, has significant activity in follicular and transformed NHL. Use of
      rituximab has proved that antibodies are safe and active even as single agents.
      The results have helped dispel the negativity and biases resulting from many
      years of disappointing results in this important area of research. Results with
      rituximab have opened the doors to continued research and have provided the
      impetus necessary for renewed enthusiasm and optimism in continuing the search
      for curative regimens for patients with NHL.

PMID- 12512833
TI  - Combination of chemotherapy and monoclonal antibodies for the treatment of
      lymphoma.
AB  - Monoclonal antibodies (MoAbs) have transformed the treatment of lymphomas. The
      first reports of studies using MoAbs appeared 8 years ago, and current therapy
      for lymphoma patients usually includes treatment with MoAbs once or several times
      during the course of their disease. This review covers the use of MoAbs in
      combination with chemotherapy for the treatment of patients with lymphoma.
      Rituximab, an unconjugated anti-CD20 chimeric antibody, is certainly the most
      widely used MoAb, but the use of other unconjugated or radiolabeled MoAbs is
      increasing quickly. MoAbs are effective if used alone, but the duration of
      effectiveness is limited. Therefore, when MoAbs are used in curative treatment,
      they are combined with chemotherapy. There are randomized studies demonstrating
      the benefit of adding MoAbs to the treatment regimen of patients with diffuse
      large B-cell lymphoma, but results of ongoing studies regarding the benefit in
      other lymphomas have not been reported. Many questions must be answered before
      the best setting for MoAbs in the treatment of lymphoma patients can be
      determined.

PMID- 12512834
TI  - Development of radioimmunotherapy for the treatment of non-Hodgkin's lymphoma.
AB  - The goal of radioimmunotherapy (RIT) is to target radiation to tumor tissue with
      radiolabeled monoclonal antibodies while limiting toxicity to normal cells.
      Radionuclide emission properties and the chemical stability of
      radioimmunoconjugates are important factors that contribute to the effectiveness
      of RIT. A 1994 review of early clinical trials with RIT in treating non-Hodgkin's
      lymphoma (NHL) reported a 40% response rate with nonmyeloablative doses of
      yttrium 90 (90Y) or iodine 131 (131I) antibodies. Of the radiolabeled antibodies
      currently in pivotal trials or approved by the US Food and Drug Administration,
      those targeted to the CD20 antigen have produced the highest response rates.
      Response rates for ibritumomab tiuxetan, the recently approved RIT for NHL,
      ranged from 74% in rituximab-refractory patients to 80% in the pivotal trial. The
      iodine-labeled anti-B1 antibody has been evaluated in previously treated and
      previously untreated patients with NHL. In the pivotal trial, previously treated
      patients achieved a response rate of 65%, whereas previously untreated patients
      had a 97% response rate. Radiolabeled anti-HLA DR has been evaluated in NHL
      patients and has demonstrated a 53% response rate. Murine antibody LL2, which
      recognizes the CD22 antigen, has been radiolabeled with 90Y and 131I, with
      response rates ranging from 15% to 33%. The development of radioimmunotherapy has
      led to meaningful advances in the treatment of B-cell NHL.

PMID- 12512835
TI  - Monoclonal antibody therapy for B-cell lymphoma: clinical trials of an anti-CD20
      monoclonal antibody for B-cell lymphoma in Japan.
AB  - Twelve patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (B-NHL) were
      enrolled in a phase I study of rituximab; 4 received rituximab 250 mg/m2 and 8
      received rituximab 375 mg/m2 once weekly for 4 weeks. Grade 1 or 2 infusion
      related toxicity was observed. Of the 11 eligible patients, 2 achieved complete
      responses and 5 achieved partial responses. The elimination half-life (T1/2) of
      rituximab was 445 +/- 361 hours, and serum rituximab levels were detectable at 3
      months. Thereafter, 90 relapse patients with indolent B-NHL or mantle cell
      lymphoma (MCL) were enrolled in a phase II study and treated with rituximab at
      375 mg/m2 per infusion in 4 weekly infusions. Sixteen patients were ineligible in
      protocol compatible analyses. The overall response rates (ORR) in indolent B-NHL
      and MCL were 61% (37 of 61 patients) and 46% (6 of 13 patients), respectively.
      Factors affecting response and progression-free survival (PFS) were analyzed for
      77 patients whose histopathology was centrally confirmed as indolent B-NHL or
      MCL. The ORR in patients receiving 1 prior chemotherapy regimen was higher than
      the ORR in those receiving > or = 2 regimens (P < .05). The median PFS was
      shorter in MCL patients, in those with extranodal disease, and in those receiving
      > or = 2 prior chemotherapy regimens (P < .01). The PFS of patients with higher
      serum rituximab levels (> or = 70 microg/mL) immediately before the third
      infusion was longer than that of other patients (P < .01). Several pretreatment
      factors and serum rituximab levels are useful for predicting the efficacy of
      rituximab monotherapy. Rituximab re-treatment was well tolerated in 13 patients
      with no grade 3 or 4 nonhematological toxicities. A partial response was observed
      in 5 patients (38%), and the median PFS after re-treatment was 5.1 months. In
      conclusion, rituximab is a highly effective agent in relapsed indolent and
      aggressive B-NHL and MCL and has acceptable toxicities.

PMID- 12512836
TI  - The control of expression of the alpha-globin gene cluster.
AB  - The alpha-globin gene cluster is located at the very tip of the short arm of
      chromosome 16. It produces the alpha-like globins, which is combined with the
      beta-like globins to form hemoglobin, and its mutants cause alpha-thalassemia,
      which is one of the most common genetic diseases. Its expression shows a tissue
      and developmental stage specificity that is balanced with that of the beta-globin
      gene cluster. In this article, we summarize the research on the control of
      expression of the alpha-globin gene cluster, mainly with respect to the alpha
      major regulatory element (alpha-MRE): HS-40, the tissue-specific and
      developmental control of its expression, and its chromosomal environment. In
      summary, the alpha-globin gene cluster is expressed in an open chromosomal
      environment; HS-40, the 5'-flanking sequence, the transcribed region, and the 3'
      flanking sequence interact to fully regulate its expression.

PMID- 12512837
TI  - Constitutive activation of c-kit by the juxtamembrane but not the catalytic
      domain mutations is inhibited selectively by tyrosine kinase inhibitors STI571
      and AG1296.
AB  - The c-kit receptor tyrosine kinase (KIT) is constitutively activated by 2 types
      of naturally occurring mutations, the Val559-->Gly (G559) mutation in the
      juxtamembrane domain and the Asp814-->Val (V814) mutation in the catalytic
      domain. We evaluated the effects of the tyrosine kinase inhibitors STI571 and
      AG1296 on BaF3 cells expressing wild-type KIT (KIT(WT)) or activating mutants of
      KIT (KIT(G559) and KIT(V814)) in the presence or absence of the KIT ligand, stem
      cell factor (SCF). Both STI571 and AG1296 inhibited SCF-dependent activation of
      KIT(WT) and SCF-independent activation of KIT(G559) more efficiently, whereas SCF
      independent activation of KIT(V814) was scarcely affected. Furthermore, both
      inhibitors inhibited SCF-dependent growth of BaF3-KIT(WT) cells and, with higher
      potencies, SCF-independent growth of BaF3-KIT(G559) cells through the induction
      of apoptosis. In contrast, the inhibitors had little or no effect on SCF
      independent growth of BaF3-KIT(V814) cells or on IL-3-dependent growth of BaF3
      Mock cells. These results suggested that both inhibitors may be effective
      therapeutic agents for oncogenic KIT with the juxtamembrane domain mutation, but
      not with the catalytic domain mutation, and that the activation mechanism of the
      catalytic domain mutant KIT is complex and entirely different from that of the
      wild-type KIT or the juxtamembrane domain mutant KIT.

PMID- 12512838
TI  - Intensified daunorubicin in induction therapy and autologous peripheral blood
      stem cell transplantation in postremission therapy (Double-7 protocol) for adult
      acute myeloid leukemia.
AB  - To investigate whether an intensified dose of daunorubicin (DNR) in induction
      therapy and autologous peripheral blood stem cell transplantation (PBSCT) in the
      postremission period are effective treatments, we used a Double-7 protocol to
      treat adult patients with de novo acute myeloid leukemia (excluding M0 and M3).
      Induction therapy consisted of 40 mg/m2 of DNR intravenous drip infusion for 7
      days and 200 mg/m2 of ara-C by continuous infusion for 7 days (7 + 7 DC regimen).
      Patients who achieved complete remission (CR) were given high-dose chemotherapy
      with autologous PBSCT in postremission therapy. Of the 22 assessable patients, 16
      attained CR (73%). Disease-free survival (DFS) and overall survival (OS) at 3
      years were 61.2% and 48.1%, respectively. Nine of the CR patients underwent PBSCT
      without therapy-related mortality. Patients in a favorable cytogenetic group (n =
      7) attained 100% CR and long-term survival (71.4% DFS and 85.7% OS at 3 years).
      Thus, intensified DNR administration of 280 mg/m2 (40 mg/m2 per day for 7 days)
      in induction therapy for adult patients younger than 60 years of age might be
      optimal or at least comparable with the new anthracyclines such as idarubicin. In
      addition, autologous PBSCT in postremission therapy might improve DFS and OS, at
      least for patients in a favorable cytogenetic group, such as those with a t(8;21)
      abnormality.

PMID- 12512839
TI  - Plasma leptin and leptin receptor expression in childhood acute lymphoblastic
      leukemia.
AB  - Recently, leptin has been shown to play a regulatory role for differentiation
      within the myeloid and erythroid cell lineage, whereas results of its regulatory
      effects on lymphocytes and related tumor cells have been contradictory. To
      investigate whether leptin plays a role in acute lymphoblastic leukemia (ALL), we
      investigated the levels of leptin in plasma with enzyme-linked immunosorbent
      assays and the expression of the leptin receptor on malignant lymphoblasts with
      reverse transcriptase polymerase chain reaction (RT-PCR). At diagnosis, the
      leptin levels of bone marrow-derived plasma in children with ALL were found to be
      significantly lower than the levels of healthy control subjects (0.92 +/- 0.79
      ng/mL versus 3.01 +/- 2.27 ng/mL, respectively). Notably, at complete hematologic
      remission (at day 33 of chemotherapy), leptin levels had normalized to 2.6 +/-
      2.4 ng/mL. To elucidate the underlying mechanism of this phenomenon, we analyzed
      the expression of the leptin receptor on the mononuclear cell populations of the
      patients. RT-PCR analysis revealed gene expression rates of 33% at diagnosis
      versus 71% at remission, compared with 100% for healthy control subjects. Results
      of immunohistochemical staining supported these findings by showing that the
      tumor clones themselves do not express the leptin receptor. Finally, some
      hypotheses that might explain the decrease of leptin levels in the presence of
      the tumor clone are discussed.

PMID- 12512840
TI  - No V(H) somatic hypermutation was detected in B-cells of a patient with
      macroglobulinemia due to splenic marginal zone lymphoma.
AB  - B-cell diseases are classified on the basis of the normal differentiation stages.
      We report here a case of a patient with a long history of leukocytosis,
      splenomegaly without lymphadenopathy, and hyperviscosity symptoms. Clinically,
      the patient's diagnosis was leukemic Waldenstrom macroglobulinemia. Chromosomal
      analysis revealed translocation t(2;7)(p11;q22) along with disease progression.
      Death occurred from pulmonary infection at 46 months after the initial
      presentation. At autopsy, malignant lymphocytes were found in the marginal areas
      of the spleen with spreading to the bone marrow and the liver. The histologic
      findings were consistent with splenic marginal zone lymphoma. We examined the
      sequences of the immunoglobulin V(H) gene in cells from the initial peripheral
      blood and from the spleen at autopsy and found that the sequences were identical
      and had no somatic hypermutation. Macroglobulinemia can occur in various B-cell
      disorders, including splenic marginal zone lymphoma, even with the transformation
      of unmutated B-lymphocytes.

PMID- 12512841
TI  - Absence of clinical prognostic value of vascular endothelial growth factor and
      microvessel density in multiple myeloma.
AB  - Vascular endothelial growth factor (VEGF) is considered a potent stimulator of
      angiogenesis. In multiple myeloma (MM), it has been reported that bone marrow
      angiogenesis parallels tumor progression and correlates with a poor prognosis. To
      investigate the role of angiogenesis in MM, we investigated VEGF expression and
      microvessel density (MVD) in the bone marrow of 75 MM patients by
      immunohistochemical methods. VEGF expression was observed in 87.3% (62 of 71) of
      patients. MVD was 69.42 +/- 9.67 (mean +/- SE) compared with the normal control
      values of 26.81 +/- 2.85. MVD values were 73.98 +/- 11.27 and 36.04 +/- 6.99 in
      the VEGF-positive and VEGF-negative groups, respectively. The MVD of patients in
      the VEGF-positive group was significantly higher than in the VEGF-negative group
      (P = .045). However, there were no significant differences in various clinical
      parameters, such as age, sex, hemoglobin, platelet count, serum levels of
      albumin, calcium, creatinine, and beta2-microglobulin, and bone marrow plasma
      cell percentage, between the VEGF-positive and VEGF-negative groups. Multivariate
      analysis revealed that age, hemoglobin, platelet count, serum levels of albumin
      and creatinine, and bone marrow plasma cell percentage were correlated with
      overall survival, whereas VEGF expression or MVD was not. In conclusion, our
      results suggest that VEGF is highly expressed and that MVD is increased in MM,
      indicating that angiogenesis may play a role in MM. Although MVD in the bone
      marrow of the VEGF-positive group is significantly higher compared with the VEGF
      negative group (P = .045), VEGF is not correlated with overall survival. Further
      studies that include other angiogenic factors are needed to determine the
      functional role of angiogenesis in MM.

PMID- 12512842
TI  - Comparison of microvessel density before and after peripheral blood stem cell
      transplantation in multiple myeloma patients and its clinical implications:
      multicenter trial.
AB  - Bone marrow angiogenesis has been reported to increase in several hematologic
      malignant diseases, including multiple myeloma. Because high-dose chemotherapy
      combined with autologous stem cell transplantation (SCT) improves the response
      rate, event-free survival, and overall survival in patients with multiple myeloma
      (MM), we studied the changes in bone marrow microvessel density (MVD) in 21
      patients who underwent high-dose chemotherapy combined with autologous SCT to
      determine whether there was persistently increased angiogenesis at the time of
      response. Bone marrow biopsy specimens were obtained before and after SCT for
      each patient and immunostained with anti-CD34 antibodies for the identification
      of microvascular endothelial cells. The mean value of MVD in 21 MM patients at
      initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P
      = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0
      +/- 12.5 after achievement of response with SCT, and there was a statistically
      significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased
      MVD after SCT, and 5 patients were found to have a greater than 50% decrease in
      MVD after SCT. However, there was no difference in overall survival between the
      patient group with decreased MVD after SCT and that without decreased MVD (P =
      .9370). These results suggest that angiogenesis plays an important role in MM. In
      addition, the persistence of MVD at the time of response indicates continuous
      stimulus of microvessels by minimal residual disease even after SCT.

PMID- 12512843
TI  - Atypical presentations of thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) usually presents in a fulminant fashion
      with marked hematologic abnormalities often associated with fever and neurologic
      and renal abnormalities. Two cases of TTP are reported in which neurologic
      deficits were initially the dominant findings, followed weeks later by the
      pronounced hematologic manifestations. Young patients with unexplained neurologic
      findings, even if there is only minimal anemia or thrombocytopenia, should be
      monitored for subsequent manifestations of TTP so that treatment may be
      instituted promptly.

PMID- 12512844
TI  - Intensive plasma IgG removal therapy for severe thrombotic thrombocytopenic
      purpura.

PMID- 12512845
TI  - Acute bacterial sinusitis in adults: management in the primary care setting.
AB  - Sinus disease is inherently associated with viral upper respiratory tract
      infections and occurs in 90% of individuals with the common cold. Acute bacterial
      sinusitis occurs in 0.5 to 2% of these individuals. Although the diagnosis of
      acute bacterial sinusitis is usually based on physical findings, no one sign or
      symptom is either sensitive or specific for sinusitis. The predictive power can
      be significantly improved when all signs and symptoms are combined into a
      clinical impression. Imaging studies have not been shown to be cost effective in
      the initial assessment and treatment of patients in the primary care setting.
      Simple plain films may be indicated to resolve the diagnosis in patients with an
      equivocal history or to follow patients admitted to hospital with severe sinus
      disease. The initial management of acute sinusitis should be directed toward the
      relief of symptoms with a 7-day course of decongestants and mucoevacuents. For
      patients who fail to improve with symptomatic treatment, a 10-day course of
      amoxicillin is recommended. Second line antibiotics should be initiated if
      improvement is not seen within 72 to 96 hours.

PMID- 12512846
TI  - Evaluation of an HIV/AIDS prevention intervention targeting Latino gay men and
      men who have sex with men in Puerto Rico.
AB  - This article presents the evaluation of an HIV prevention model and intervention
      targeting Latino gay males and men who have sex with men in Puerto Rico. Based on
      the health belief model in combination with concepts of self-efficacy, cognitive
      theory, and community development, a series of workshops were developed to
      enhance safer sex behavior among participants. A total of 587 men recruited by
      availability in gay meeting places and through peer referral participated in the
      intervention between 1992 and 1995. Participants engaged in a 3-hour small group
      meeting and four 3-hour workshops as part of the intervention. Pretests and
      posttests were administered to measure knowledge, attitudes, and behaviors
      related to HIV infection; a risk index was calculated to measure the level of
      behavior risk for HIV infection. Participants demonstrated lower risk indexes
      after the intervention. This model represents a culturally competent and relevant
      intervention for similar communities.

PMID- 12512847
TI  - Ethnic and gay community attachments and sexual risk behaviors among urban Latino
      young men who have sex with men.
AB  - Culturally relevant prevention programs are required to reduce HIV risk exposure
      of Latino young men who have sex with men (YMSM). As part of Hermanos Jovenes,
      465 Latino YMSM were surveyed at community venues of New York City outside the
      gay-identified area of lower Manhattan. We examined factors that influence ethnic
      and gay community attachments; the association between community attachments and
      social support in sexual matters; and the relationship between levels of
      attachment, social support in sexual matters, and sexual risk behaviors. Sixty
      eight percent felt closely connected to their ethnic community; about 34% were
      highly attached to both neighborhood and New York City gay communities. Greater
      social support in sexual matters was associated with ethnic and gay community
      attachments. Latino YMSM connected to their ethnic community were about 40% less
      likely to report recent unprotected anal intercourse (UAI) with a male partner,
      and 60% less likely to have engaged in UAI during the last sexual contact with a
      nonmain male partner. Gay community attachment was not significantly related to
      risk behaviors. Findings point to the importance of ethnic ties and involving
      ethnic community organizations in HIV prevention efforts.

PMID- 12512848
TI  - Unprotected sex and associated risk factors among young Asian and Pacific
      Islander men who have sex with men.
AB  - Young Asian and Pacific Islander (API) men who have sex with men (MSM) are at
      high risk for HIV, but little is known about their risk behavior. We examined the
      patterns and predictors of unprotected anal intercourse among 253 API MSM aged 15
      25 recruited from gay-identified venues in Seattle, Washington, and San Diego,
      California, from May to August 1999. Overall, 33% reported unprotected anal
      intercourse in the past 3 months. Multivariate analyses found that unprotected
      anal intercourse was associated with self-identifying as gay or bisexual, having
      multiple sexual partners, having sex with a steady partner, having been tested
      for HIV, and not perceiving peer norms supportive of safer sex. Young API MSM
      engage in unprotected sex at high rates. There is an urgent need to help these
      men reduce sexual risk behavior by implementing HIV prevention programs that
      address the issue of self-accepting sexual orientation, the potential problem
      with using HIV testing as a risk reduction strategy, the possible risk of HIV
      transmission in steady relationships and multiple sexual partnerships, and the
      importance of establishing safer sex practices as peer norms.

PMID- 12512849
TI  - Being high and taking sexual risks: findings from a multisite survey of urban
      young men who have sex with men.
AB  - Adolescent and young adult males who have sex with men (MSM) remain at high risk
      of HIV infection. Many sexual risk factors have been identified, yet the role of
      substance use remains controversial. We assess the extent to which urban young
      MSM report being "high" on drugs or alcohol during sex and the association
      between being "high" and unprotected anal intercourse (UAI). During summer 2000,
      3,075 MSM aged 15-25 years completed a 20-minute interview for the Community
      Intervention Trial for Youth Project. Participants were asked about their last
      sexual contact with main and nonmain partners, including whether they were "high
      on drugs or alcohol." 18.6% of MSM with a main partner reported being high during
      their last sexual encounter; 25.0% reported UAI. Among men with a nonmain
      partner, 29.3% reported being high, and 12.3% reported UAI. Being high was
      associated with unprotected receptive anal intercourse with nonmain partners
      (odds ratio = 1.66, p = .02). HIV prevention should include messages about the
      potential dangers of drinking and drug use in situations where sexual encounters
      with nonmain partners may occur.

PMID- 12512850
TI  - Social influence, AIDS/STD knowledge, and condom use among male clients of female
      sex workers in Bali.
AB  - The importance of social networks is increasingly being recognized in research on
      HIV risk behaviors. The objective of this article is to examine the association
      of AIDS and sexually transmitted disease (STD) knowledge, perceived
      susceptibility to HIV/STD infection, condom beliefs, demographic variables, and
      peer influence on the condom use of clients of Indonesian sex workers. Data for
      the study are drawn from the Bali STD/AIDS study conducted from 1997 to 1999 in
      Bali, Indonesia. During the project 2,026 men were selected for interviews in low
      price brothels. Statistical methods included multivariate regression models.
      Results of the study showed that younger men, men who have resided in Bali for at
      least a year, and more educated men were more likely to use condoms. Furthermore,
      men with stronger AIDS and STD knowledge and condom beliefs were more likely to
      use condoms. Men whose friends knew that they visited sex workers were less
      likely to use condoms. However, men who reported that their friends used condoms
      with sex workers and that their friends encouraged them to use condoms with sex
      workers were more likely to use condoms with sex workers. Implications for
      prevention of HIV infection are discussed.

PMID- 12512851
TI  - Increasing condom use by undermining perceived invulnerability to HIV.
AB  - An intervention to increase condom use by undermining perceptions of
      invulnerability to HIV was tested in a sample of 128 college students.
      Participants were randomly assigned to the invulnerability undermined (IU)
      condition or a demand characteristic control (DCC) condition. The IU condition
      used tasks that highlighted past failures to protect oneself and the failure of
      illusory protection strategies. Participants in the DCC condition watched a video
      on protecting oneself from HIV. Participants in the IU condition, relative to
      those in the DCC group, had lower perceptions of invulnerability to HIV and
      higher intentions to use condoms on the immediate postintervention measures; they
      reported more condom use at the 3-month follow-up. Contrary to prediction,
      perceptions of invulnerability did not mediate the effects of the intervention on
      condom use intentions or condom use. The advantage of indirect methods of
      reducing denial of vulnerability is discussed.

PMID- 12512853
TI  - PM speech: 'science matters.'.

PMID- 12512852
TI  - Action control and situational risks in the prevention of HIV and STIs:
      individual, dyadic, and social influences on consistent condom use in a
      university population.
AB  - The aim of this study was to gain an understanding of consistent condom use. We
      took the perspective that condom use involves the ability to handle situational
      risks influenced at multiple levels, including the individual, dyadic, and
      social. The hypothesis was that action control, as measured by self-regulation,
      implementation intentions, and self-efficacy, was the primary determinant. The
      study was conducted at part of a community-based intervention at a major
      university (36,000 students). Data was collected using a validated questionnaire
      mailed to a random sample of students (n = 493, response rate = 71.5%).
      Statistical analysis included logistic regression models that successively
      included background, individual, dyadic, and social variables. In the final
      model, consistent condom use was higher among students with strong implementation
      intentions, high self-regulation and positive peer norms. The results contribute
      new knowledge on action control in predicting sexual risk behaviors and lends
      support to the conceptualization and analysis of HIV/sexually transmitted
      infection prevention at multiple levels of influence.

PMID- 12512854
TI  - Dispatches from the last frontier of molecular and cell biology: biosynthesis of
      polysaccharides and proteoglycans of the cell surface and extracellular matrix.

PMID- 12512855
TI  - Heparin and heparan sulfate biosynthesis.
AB  - Heparan sulfate is one of the most informationally rich biopolymers in Nature.
      Its simple sugar backbone is variously modified to different degrees depending on
      the cellular conditions. Thus, it matures to have an enormously complicated
      structure, which most likely exhibits a considerable number of unique overlapping
      sequences with peculiar sulfation profiles. Such sequences are recognized by
      specific complementary proteins, which form a huge group of "heparin-binding
      proteins," and the sugar sequences in turn support unique functions of the
      respective proteins through specific interactions. The heparan sulfate sequences
      are not directly encoded by genes, but are created by elaborate biosynthetic
      mechanisms, which ensure the generation of these indispensable sequences. In
      heparan sulfate biosynthesis, the tetrasaccharide sequence (GlcA-Gal-Gal-Xyl-),
      designated the protein linkage region, is first assembled on a specific Ser
      residue at the glycosaminoglycan attachment site of a core protein. A heparan
      sulfate chain is then polymerized on this fragment by alternate additions of
      GlcNAc and GlcA through the actions of glycosyltransferases with overlapping
      specificities encoded by the tumor suppressor EXT family genes. Then follow
      various modifications by N-deacetylation and N-sulfation of glucosamine, C5
      epimerization of GlcA and multiple O-sulfations of the component sugars. Recent
      studies have achieved purification of several, and molecular cloning of most, of
      the enzymes responsible for these reactions. Some of these enzymes are
      bifunctional. The availability of cDNA probes has facilitated elucidation of the
      crystal structures for two of the biosynthetic enzymes, demonstration of their
      intracellular location, and their occurrence in complexes to achieve rapid and
      efficient synthesis of complex sugar sequences. Genomic structure and transcript
      analysis have shown the existence of multiple isoforms for most of the
      sulfotransferases. Many aspects of the heparan sulfate biosynthetic scheme are
      shared by the structural analog heparin, which is synthesized in mast cells and
      some other mammalian cells and is several-fold higher degree of polymerization
      and more extensive modification than heparan sulfate.

PMID- 12512856
TI  - Biosynthesis of chondroitin/dermatan sulfate.
AB  - Chondroitin sulfate and dermatan sulfate are synthesized as galactosaminoglycan
      polymers containing N-acetylgalactosmine alternating with glucuronic acid. The
      sugar residues are sulfated to varying degrees and positions depending upon the
      tissue sources and varying conditions of formation. Epimerization of any of the
      glucuronic acid residues to iduronic acid at the polymer level constitutes the
      formation of dermatan sulfate. Chondroitin/dermatan glycosaminoglycans are
      covalently attached by a common tetrasaccharide sequence to the serine residues
      of core proteins while they are adherent to the inner surface of endoplasmic
      reticulum/Golgi vesicles. Addition of the first sugar residue, xylose, to core
      proteins begins in the endoplasmic reticulum, followed by the addition of two
      galactose residues by two distinct glycosyl transferases in the early cis/medial
      regions of the Golgi. The linkage tetrasaccharide is completed in the
      medial/trans Golgi by the addition of the first glucuronic acid residue, followed
      by transfer of N-acetylgalactosamine to initiate the formation of a
      galactosaminoglycan rather than a glucosaminoglycan. This specific N
      acetylgalactosaminyl transferase is different from the chondroitin synthase
      involved in generation of the repeating disaccharide units to form the
      chondroitin polymer. Sulfation of the chondroitin polymer by specific
      sulfotransferases occurs as the polymer is being formed. All the enzymes in the
      pathway for synthesis have been cloned, with the exception of the glucuronyl to
      iduronyl epimerase involved in the formation of dermatan residues.

PMID- 12512857
TI  - Keratan sulfate biosynthesis.
AB  - Keratan sulfate was originally identified as the major glycosaminoglycan of
      cornea but is now known to modify at least a dozen different proteins in a wide
      variety of tissues. Despite a large body of research documenting keratan sulfate
      structure, and an increasing interest in the biological functions of keratan
      sulfate, until recently little was known of the specific enzymes involved in
      keratan sulfate biosynthesis or of the molecular mechanisms that control keratan
      sulfate expression. In the last 2 years, however, marked progress has been
      achieved in identification of genes involved in keratan sulfate biosynthesis and
      in development of experimental conditions to study keratan sulfate secretion and
      control in vitro. This review summarizes current understanding of keratan sulfate
      structure and recent developments in understanding keratan sulfate biosynthesis.

PMID- 12512858
TI  - Mammalian hyaluronan synthases.
AB  - Three mammalian hyaluronan (HA) synthase genes, HAS1, HAS2, and HAS3, have been
      cloned and expressed, allowing the mechanisms for regulation of HA biosynthesis
      and function to be studied. The hyaluronan synthase (HAS) isoforms differ in
      kinetic characteristics and product size. The expression of each HAS isoform is
      controlled in a different fashion when mammalian cells are stimulated by various
      cytokines and the expression patterns are both spatially and temporally regulated
      during embryonic development. The existence of three different HAS isoforms with
      different characteristics implies that the broad range of biological and
      physiological roles performed by HA are regulated by controlling the activities
      and expression of the HAS isoforms. This review focuses on recent findings on the
      regulatory mechanisms for controlling HA biosynthesis and provides new insights
      into the enzymic basis for the functional regulation of HA.

PMID- 12512859
TI  - Functional characteristics and catalytic mechanisms of the bacterial hyaluronan
      synthases.
AB  - The first gene for a glycosaminoglycan synthase to be cloned was the hyaluronan
      (HA) synthase from S. pyogenes, which we reported in 1993. Since then, at least
      20 bacterial, viral, or eukaryotic HA synthase gene or cDNA sequences and two
      bacterial chondroitin synthase genes have been reported. During the last decade a
      great deal has been elucidated about the structure, function, and mechanisms of
      action of the bacterial HA synthases, which are the focus of this review. Very
      rapid progress has been made in elucidating the mechanism of HA synthesis by the
      HA synthase from Pasteurella multocida. Although little of this information is
      applicable to understanding the mechanism of action of streptococcal HA
      synthases, good progress has also been made in understanding how these latter
      enzymes work.

PMID- 12512860
TI  - Phenomenological perspectives on the folding of beta/alpha-barrel domains through
      the modular formation and assembly of smaller structural elements.
AB  - The beta/alpha-barrel motif was once considered to be a single protein domain. In
      recent years, however, it has been shown to consist of smaller substructures
      displaying the ability to fold autonomously. Here we review the current status of
      experimental findings concerning the motif's folding behavior in the light of
      what is currently known about (a) the relative rates of formation of helices and
      sheets in proteins, in general, and (b) the peculiarities of topology and
      architecture of the motif, in particular, to develop a detailed phenomenological
      understanding of how beta/alpha-barrels might form through the modular folding
      and assembly of substructures.

PMID- 12512861
TI  - May monomeric proteins be allosterically controlled?

PMID- 12512862
TI  - How I became a biochemist.

PMID- 12512863
TI  - Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox
      reactions, and methods for their quantification.
AB  - Reactive oxygen species (ROS) and other radicals are involved in a variety of
      biological phenomena, such as mutation, carcinogenesis, degenerative and other
      diseases, inflammation, aging, and development. ROS are well recognized for
      playing a dual role as deleterious and beneficial species. The objectives of this
      review are to describe oxidative stress phenomena, terminology, definitions, and
      basic chemical characteristics of the species involved; examine the biological
      targets susceptible to oxidation and the defense mechanisms of the organism
      against these reactive metabolites; and analyze methodologies, including
      immunohistochemical markers, used in toxicological pathology in the visualization
      of oxidative stress phenomena. Direct detection of ROS and other free radicals is
      difficult, because these molecules are short-lived and highly reactive in a
      nonspecific manner. Ongoing oxidative damage is, thus, generally analyzed by
      measurement of secondary products including derivatives of amino acids, nuclei
      acids, and lipid peroxidation. Attention has been focused on electrochemical
      methods based on voltammetry measurements for evaluating the total reducing power
      of biological fluids and tissues. This approach can function as a tool to assess
      the antioxidant-reducing profile of a biological site and follow changes in
      pathological situations. This review thus includes different topics essential for
      understanding oxidative stress phenomena and provides tools for those intending
      to conduct study and research in this field.

PMID- 12512864
TI  - Diet and kidney diseases in rats.
AB  - Diet-associated kidney diseases of rats includes nephropathy in both sexes and
      nephrocalcinosis in females. High protein content of diets appears to be the
      major cause for severe nephropathy and changing the source of protein to one such
      as soy protein, restricting caloric intake, or modifying the diet to decrease
      protein consumption could decrease the severity of nephropathy. The NTP-2000 diet
      with lower protein content than most diets decreases the severity of nephropathy
      and increases the survival of Fischer 344 rats without substantial changes in
      growth patterns and body weights. Nephrocalcinosis, characterized by
      mineralization of renal tubules at the corticomedullary junction, has been
      reported in young and adult female rats of most strains and stocks suggesting a
      major contribution of female sex hormones to the development of this lesion.
      Calcium (Ca), phosphorous (P), magnesium (Mg), and chloride (Cl) imbalances,
      especially a Ca:P ratio of less than 1.0 in diet, are considered to be associated
      with this lesion. Most commercial diets commonly used for toxicology studies have
      a Ca:P molar ratio of less than 1.0. Increasing the Ca:P molar ratio to more than
      1.0 and closer to 1.3 in the AIN-93 purified diet and NTP-2000 nonpurified diet
      prevents the development of this lesion. Genetics will predispose rats to some
      diseases and environmental factors will influence the severity of these diseases.
      Diet is one of the most important environmental factors. Diets balanced for
      nutrients without excesses could markedly improve the health of rats used in
      chronic studies leading to substantial increases in survival and thereby
      accomplish the objective of chronic toxicity and carcinogenicity studies.

PMID- 12512865
TI  - Characteristics of the spectrum of proliferative lesions observed in the kidney
      and urinary bladder of Fischer 344 rats and B6C3F1 mice.
AB  - Many rodent renal and bladder carcinogens rely upon epigenetic mechanisms of
      carcinogenesis; such mechanisms are likely to influence the spectrum of urinary
      tract tumors observed in control and treated animals. This is reflected in
      several features of chemically induced rodent urinary tract neoplasms, including
      a low overall tumor incidence, an increased prevalence of urinary tract tumors in
      rats compared to mice and males compared to females, the tendency for epithelial
      tumors to predominate over nonepithelial types, and demonstrated links to chronic
      progressive nephropathy and urolithiasis. Such tendencies are also characteristic
      of spontaneous urinary tract tumors in rodents. Data to support these
      observations can be derived from large historical databases such as the
      Toxicology Data Management System, maintained by National Toxicology Program.

PMID- 12512866
TI  - Comparative pathology of proliferative lesions of the urinary bladder.
AB  - Bladder neoplasia in humans consists of 2 diseases, a low-grade papillary tumor
      that does not invade or metastasize, and a high-grade lesion that usually invades
      and metastasizes. Bladder carcinogenesis in rats is most like the low-grade,
      papillary tumor, although it eventually does progress and invade. In the mouse,
      models are available that mimic each of these disease processes. Preneoplastic
      lesions in humans and rodents include various types of hyperplasia, proliferative
      cystitis, and dysplasia. These preneoplastic and neoplastic lesions arise
      throughout the urothelium, from the renal pelvis to the urethra, although most
      commonly in the bladder. Rarely, benign and malignant mesenchymal lesions occur
      in rats and mice, with a unique submucosal mesenchymal lesion present in some
      strains of mice. In addition, eosinophilic and clear inclusions in the
      superficial layer of urothelium in mice, which do not appear to be associated
      with toxicity or carcinogenesis, have been reported. An approach to evaluation of
      carcinogenic mechanisms involved in the urothelium is presented. It focuses on
      distinguishing between DNA reactive carcinogens vs those that act by increasing
      cell proliferation. Although rodent models do not precisely mimic the human
      disease, they have provided useful models for furthering our understanding of the
      carcinogenic process in the urothelium as it pertains to human diseases.

PMID- 12512867
TI  - Renal papillary necrosis.
AB  - Renal papillary necrosis (RPN) is a significant problem in human beings,
      especially in England and in Australia where it has been reported to account for
      15% to 20% of patients needing renal transplants. Many compounds, including
      aspirin, phenacetin, phenylbutazone, indomethacin, mefenamic acid, flufenamic
      acid, fenoprofin, naproxen, and ibuprofen have been linked to renal papillary
      necrosis in human beings. Although the exact mechanism of RPN is unknown, there
      are several theories that have good scientific evidence behind them. Study of RPN
      in animals as models for the disease in human beings is limited by several
      factors, including anatomical differences between human beings and most animal
      species as well as technical difficulties in studying the renal papilla.

PMID- 12512868
TI  - Use of the spontaneous Tsc2 knockout (Eker) rat model of hereditary renal cell
      carcinoma for the study of renal carcinogens.
AB  - The kidney is a frequent site for chemically induced cancers in rodents and among
      the 10 most frequent sites for cancer in human patients. Renal cell carcinoma
      (RCC) is the most frequent upper urinary tract cancer in humans and accounts for
      80-85% of malignant renal tumors. Hereditary RCC occurs in Eker rats that are
      heterozygous for an insertion mutation in the Tsc2 tumor suppressor gene. The
      germline mutation renders heterozygous mutants highly susceptible to renal
      carcinogens. The utility of this model in studying potential renal carcinogens is
      due to an ordered progression of proliferative renal lesions that can be
      identified and counted microscopically. The quantitative nature of the model
      allows for the production of statistically powerful data to understand the
      relative degree and potency of chemical effects and allow analysis of genetic
      alterations that may be chemical specific.

PMID- 12512869
TI  - The effect of chronic progressive nephropathy on the incidence of renal tubule
      cell neoplasms in control male F344 rats.
AB  - Chronic progressive nephropathy (CPN) is the most frequently diagnosed lesion in
      the rat kidney. It has many components including degeneration and regeneration of
      renal tubule (RT) epithelium, glomerular lesions and interstitial inflammation
      and fibrosis. The incidence and severity of CPN is strain, age, and sex dependent
      and may be altered by a number of factors including exposure to xenobiotics. In
      National Toxicology Program (NTP) 2-year bioassays, xenobiotic-associated
      increased severity (exacerbation) of CPN often occurs in association with a
      marginal increased incidence of renal tubule cell neoplasms (RTCN). The
      relationship between CPN and RTCN development has not been definitively
      determined. The present study evaluated the association between severity of CPN
      and the occurrence of RTCN in control male F344 rats. A slight but statistically
      significant increase in CPN severity was present in those animals with RTCN
      compared to aged-matched controls without RTCN. Although these data suggest there
      is a positive correlation between CPN and RTCN, cause and effect were not
      determined. This marginal association suggests that the number of RTCNs that may
      develop secondary to chemically exacerbated nephropathy would be few.

PMID- 12512870
TI  - A 13-week subchronic intravaginal toxicity study of the novel broad-spectrum anti
      HIV and spermicidal agent, N-[2-(1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]
      thiourea (PHI-346) in mice.
AB  - The nonnucleoside inhibitor (NNI) of HIV-1 reverse transcriptase, PHI-346 (N-[2
      (1-cyclohexenyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea), is a dual-function
      spermicidal agent with potent anti-HIV activity against drug-sensitive as well as
      drug-resistant HIV-1 strains with genotypic and phenotypic NNI resistance. PHI
      346 was formulated via a lipophilic gel-microemulsion for intravaginal use as a
      potential dual-function microbicide. To evaluate the toxicity potential of short
      term intravaginal exposure to PHI-346, groups of 15 female B6C3F1 and CD-1 mice
      were exposed intravaginally to a gel-microemulsion containing 0, 0.5, 1.0, or
      2.0% PHI-346, 5 days per week for 13 consecutive weeks. On a molar basis, these
      concentrations of PHI-346 are 350 to 1,400-times higher than its spermicidal EC50
      and nearly 5 x 10(6) to 2 x 10(7) times higher than its in vitro anti-HIV IC50.
      After 13 weeks of intravaginal treatment, B6C3F1 mice were evaluated for
      survival, body weight gain, absolute and relative organ weights. Blood was
      analyzed for hematology and clinical chemistry profiles. Microscopic examination
      was performed on hematoxylin and eosin-stained tissue sections from each study
      animal. Placebo control and PHI-346 dosed female CD-1 mice were mated with
      untreated males in order to evaluate if PHI-346 has any deleterious effects on
      the reproductive performance. There were no treatment-related mortalities. Mean
      body weight gain during the dosing period was not reduced by PHI-346 treatment.
      The hemogram or blood chemistry profiles revealed lack of systemic toxicity
      following daily intravaginal instillation of PHI-346 for 13 weeks. No clinically
      significant changes in absolute and relative organ weights were noted in PHI-346
      dose groups. Extensive histopathological examination of tissues revealed no
      treatment-related abnormalities in any of the three PHI-346 dose groups. Repeated
      intravaginal exposure of CD-1 mice to increasing concentrations of PHI-346 for 13
      weeks had no adverse effect on their subsequent reproductive capability,
      perinatal outcome, growth, and development of offspring. Collectively, these
      findings demonstrate that repetitive intravaginal administration of PHI-346 at
      concentrations as high as 1,400-times its spermicidal EC50 and 2 x 10(7) times
      its in vitro anti-HIV IC50 was not associated with local or systemic toxicity and
      did not adversely affect the reproductive performance in mice. PHI-346 may be
      useful as an active ingredient of a safe vaginal microbicide for prevention of
      the sexual transmission of multidrug-resistant HIV-1.

PMID- 12512871
TI  - Toxicity and carcinogenicity studies of chlorpromazine hydrochloride and p
      cresidine in the p53 heterozygous mouse model.
AB  - The carcinogenic potential of chlorpromazine hydrochloride, a psychotropic agent,
      was assessed in the p53 heterozygous mouse assay. In a 4-week dose range finding
      study in p53 wild-type mice, doses of 20,40, 60, and 80 mg/kg were poorly
      tolerated because of mortality secondary to the severe sedative and hypotensive
      effects of chlorpromazine. Based on 40% mortality at a dose of 20 mg/kg in the
      dose-range finding study, a high dose of 10 mg/kg was chosen for the 26-week
      carcinogenicity study in p53 heterozygous mice. Doses of 2.5, 5, and 10 mg/kg
      chlorpromazine hydrochloride were well tolerated in the 26-week study. The
      administration of chlorpromazine hydrochloride at dose levels up to and including
      10 mg/kg to p53 heterozygous and wild-type mice did not result in a dose-related
      increase in tumor incidence or in the type of tumors seen in comparison to
      controls. Findings related to the administration of chlorpromazine in the 26-week
      study were limited to minimal uterine and ovarian atrophy in p53 wild-type mice
      dosed with 10 mg/kg chlorpromazine hydrochloride. However, p53 heterozygous mice
      administered 400 mg/kg p-cresidine, a genotoxic carcinogen commonly used as a
      positive control for this model, developed urinary bladder tumors. Administration
      of p-cresidine also resulted in a regenerative anemia, splenic and hepatic
      hemosiderosis, renal findings, and ovarian and uterine atrophy. This study
      demonstrated that chlorpromazine hydrochloride, at the doses tolerated, was not
      carcinogenic in the p53 heterozygous mouse assay.

PMID- 12512872
TI  - FasL deficiency enhances the development of tumors in p53+/- mice.
AB  - In the multistep process of tumor development, several events occur to transform
      cells from normal to malignant. Although p53 is one of the most commonly mutated
      genes in a wide variety of tumors, how other genes interact with p53 to transform
      cells is only just beginning to be understood. To study the effects of the
      interaction of the Fas system with p53 in tumor progression and development, mice
      with a targeted disruption of the p53 tumor supressor gene and a mutation in Fas
      ligand were bred. Organ weights, life expectancy, and tumor and tissue histology
      were assessed. Although spleen weights were drastically increased in FasL -/- p53
      -/- mice, the FasL deficiency had no effect on life expectancy or the tumor
      spectrum of homozygous p53-deficient mice. The FasL deficiency reduced the median
      time to death from 12.1 months in FasL +/+ p53 +/- mice to 9.6 months in FasL -/-
      p53 +/- mice, and led to a shift in tumor spectrum from predominantly sarcomas
      (63%) when FasL was present to a large number of lymphomas (76%) in FasL -/- p53
      +/- mice. Given the reduced life span and increased incidence of lymphoma in FasL
      -/- p53 +/- mice, these mice could be useful in carcinogenicity testing,
      particularly for understanding mechanisms of compounds that are nongenotoxic.

PMID- 12512873
TI  - An autopsy case of minamata disease (methylmercury poisoning)--pathological
      viewpoints of peripheral nerves.
AB  - The outbreak of methylmercury poisoning in the geographic areas around Minamata
      Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on
      earlier reports and extensive pathological studies on autopsied cases at the
      Kumamoto University School of Medicine, destructive lesions in the anterior
      portion of the calcarine cortex and depletion predominantly of granular cells in
      the cerebellar cortex came to be recognized as the hallmark and diagnostic
      yardstick of methylmercury poisoning in humans. As the number of autopsy cases of
      Minamata disease increased, it became apparent that the cerebral lesion was not
      restricted to the calcarine cortex but was relatively widespread. Less severe
      lesions, believed to be responsible for the motor symptoms of Minamata patients,
      were often found in the precentral, postcentral, and lateral temporal cortices.
      These patients also frequently presented with signs of sensory neuropathy
      affecting the distal extremities. Because of few sufficiently comprehensive
      studies, peripheral nerve degeneration has not been universally accepted as a
      cause of the sensory disturbances in Minamata patients. The present paper
      describes both biopsy and autopsy findings of the peripheral nerves in a male
      fisherman who died at the age of 64 years and showed the characteristic central
      nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with
      electron microscopy performed 1 month prior to his death showed endoneurial
      fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural
      nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of
      Bungner's bands. The spinal cord showed Wallerian degeneration of the fasciculus
      gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia.
      These findings support the contention that there is peripheral nerve degeneration
      in Minamata patients due to toxic injury from methylmercury.

PMID- 12512874
TI  - Methylmercury poisoning in common marmosets--MRI findings and peripheral nerve
      lesions.
AB  - Common marmosets were used as model animals for methylmercury (MeHg) poisoning.
      Six marmosets were given MeHg of 5 ppm Hg in drinking water. The animals were
      divided into 3 groups of 2 each. The first group was examined for acute
      symptomatic MeHg poisoning. They were given MeHg for 70 and 90 days,
      respectively, to manifest severe symptoms. The second group was sacrificed after
      38 days of MeHg exposure, when they had acute-subclinical MeHg poisoning. The
      third group of animals was exposed for 21 days, and then observed for 2.5 years
      without MeHg exposure. One of them showed typical symptoms of MeHg poisoning
      after MeHg exposure had ended, but the other one showed only slight symptoms
      without ataxia. This experiment demonstrated that MeHg causes pathological
      changes in neural tissues including the peripheral nerves in common marmosets.
      Furthermore, common marmosets were found to show MeHg-induced pathological
      changes similar to those in humans in the cerebrum and cerebellum.

PMID- 12512875
TI  - Suggested Standard Operating Procedures (SOPs) for the preparation of electron
      microscopy samples for toxicology/pathology studies in a GLP environment.
AB  - We provide a set of Standard Operating Procedures (SOPs) for preparing samples
      for electron microscopic evaluation that allow storage of samples in the primary
      fixative for at least 17 years without noticeable degradation, do not compromise
      the ability to prepare the same samples for standard light microscopic
      evaluation, and provide tips for orientation of samples that may be necessary for
      evaluation. Guidelines for proper sample size, buffer composition, and fluid
      concentrations during processing are given. The impact of these procedures on
      specimen quality, ability to produce truly comparable samples for drug
      development studies, and ways to minimize time spent by technicians preparing
      these samples during necropsies is evaluated. Although many laboratories
      routinely employ most of these techniques, this compilation will facilitate the
      simultaneous light and electron microscopic preparation by the pathologist of
      comparable specimens that can be stored long-term at 4 degrees C in McDowell's
      and Trump's 4F:1G fixative (4F:1G).

PMID- 12512876
TI  - Epithelial-induced intrapulpal denticles in B6C3F1 mice.
AB  - Multiple intrapulpal denticles were observed in maxillary incisors of control and
      treated B6C3F1 mice used in a chronic inhalation study. Histologically, the
      denticles originated from multiple small budlike projections emanating from the
      epithelial sheath, immediately adjacent to the pulp chamber. The denticles were
      round to ovoid in shape with a central cavity surrounded by tubular dentin.
      Immature denticles contained epithelial cells within the central cavity, whereas
      mature denticles were either devoid of cells or contained cell fragments. A layer
      of columnar odontoblasts surrounded the outer surface of each denticle. Denticles
      advanced in a coronal direction as the incisors grew. With continued incisor
      growth, some denticles impacted the tooth wall and were associated with defects
      in dentinogenesis, altered tooth shape, and microfractures. Some denticles became
      partly or entirely incorporated into the dentin of the tooth. Intrapulpal
      denticle formation may represent a previously unidentified alteration that could
      contribute to the development of dental dysplasia in mice by interfering with
      normal tooth development and predisposing affected teeth to malformation and
      biomechanical failure with fracture.

PMID- 12512877
TI  - Isolated hemoperfused slaughterhouse livers as a valid model to study
      hepatotoxicity.
AB  - Different models of isolated and perfused livers and precision cut liver slices
      have been developed for studies on liver toxicology the past years. As most of
      these models were limited by nonphysiologic settings, a new model of normothermic
      hemoperfused isolated porcine slaughterhouse livers to examine hepatotoxicity was
      established encompassing the advantages of slaughterhouse organs to reduce animal
      experiments and autologous blood as an optimal perfusate. As model compound, the
      analgesic substance diclofenac was used and the effects of this drug on organ
      function parameters were compared to an untreated control group. Using an amount
      of 2,000 ml, the organs were perfused over 180 minutes, metabolically controlled
      via a dialysis and oxygenation system and various hematological and hepatic
      parameters were examined. In contrast to the untreated control organs,
      significant differences were found in the diclofenac group for parameters such as
      lactate, creatinine, ALT, bicarbonate, or bile flow. In summary, the presently
      established model of isolated hemoperfused slaughterhouse livers displays a
      useful new approach to assess hepatotoxicity of different substances on the organ
      level. As a major economic advantage in comparison to setups using laboratory
      animals, the new model can be run with blood and organs obtained from
      slaughterhouse animals.

PMID- 12512878
TI  - Comments on Foster, P., and McIntyre, B. (2002). Endocrine active agents:
      implications of adverse and non-adverse changes. Toxicol Pathol 30(1): 59-65.

PMID- 12512879
TI  - Variation in oral volatile sulphur compound formation.
AB  - It has been suggested that the level of orally produced volatile sulphur
      compounds (VSCs) can be of use when monitoring oral malodour or in determining
      patients at risk of periodontal disease in longitudinal studies. It is not known,
      however, to what extent the level of VSC in mouth air is a stable, individual
      characteristic over time. AIM: The hypothesis to be tested was that the level of
      VSC in mouth air is an individual trait that is stable over time. METHODS: Two
      groups of dental students participated in the study (n = 30 and n = 11). The
      amount of available substrate for VSC formation was standardized by rinses with 6
      mM aqueous solutions of cysteine (pH 7.2). Part 1 used a Haliineter to measure
      'morning breath' and response to cysteine rinses. Part 2 measured response to
      cysteine rinsing using a gas chromatograph. Repeated measurements provided
      information concerning the longitudinal intra-individual variations in level of
      oral VSC formation. RESULTS: Both groups showed large intra-individual variations
      in oral VSC. The differences were enhanced by cysteine rinses. CONCLUSION: The
      hypothesis was not supported. Oral VSC levels cannot be taken as diagnostic
      criteria in a normal population because of marked intra-individual variations
      over time.

PMID- 12512880
TI  - Reasons for replacement and the age of failed restorations in posterior teeth of
      young Finnish adults.
AB  - Using dentist characteristics, our aim was to evaluate the reasons for
      replacements of fillings, the age of failed restorations in the posterior teeth
      of young adults, and replacement rates. Altogether 205 patient records from the
      Public Oral Health Service of the City of Vantaa, Finland were evaluated. Patient
      age was restricted to between 25 and 30 years and type of tooth to posterior
      teeth only (third molars excluded). Information collected from the records
      included the patient's date of birth, latest DMFS and DMF, and the code for
      background data on the dentist. Details of each filled premolar and molar
      included the restorative material, location, and surface coverage of filling(s).
      The age of replacement of filling in premolar(s) or molar(s) was screened
      retrospectively from patient records. The total number of filled premolars and
      molars was 1873, with 1969 fillings. Forty percent of the patients had undergone
      replacement of filling in premolar(s) or molar(s). In all, 140 replacements had
      been made, accounting for 6.9% of amalgam fillings and 8.5% of tooth-colored
      fillings. Secondary caries, along with fractures, overhangs, and marginal
      discrepancy, was the most common reason for replacement. The mean age of failed
      amalgam fillings was 8.9 years (SD 5.2) and of failed tooth-colored fillings 2.4
      years (SD 1.6). In the public sector, female dentists form the majority and their
      replacement rate for amalgam fillings was twice that of male dentists (7.6% vs
      3.2%; P = 0.01).

PMID- 12512881
TI  - Assessments of oral health care in dependent older persons in nursing facilities.
AB  - The number of dependent elderly with natural teeth is increasing dramatically. If
      these elderly persons do not receive proper oral health care, severe oral
      problems are likely to result. In conjunction with an oral health care education
      program for the staff of nursing facilities, oral health status was assessed and
      semi-structured interviews performed with residents and their relatives about
      oral health care. The assessments were made at baseline and at an 18-month follow
      up. The project was conducted as a longitudinal, controlled study with an
      intervention and a control group. The aim of the study was to evaluate
      differences between the intervention and control group after oral health care
      intervention. At follow-up, it was shown that the intervention group had
      established more dental contacts. However, the results also indicated that the
      residents were not concerned about their oral health. Nursing staff therefore
      have to be responsible for oral health care if improved care for residents is to
      be realized.

PMID- 12512882
TI  - Is tooth agenesis related to brainstem anomalies in myelomeningocele patients
      with Chiari II malformations?
AB  - Defects in the prenatal development of the brainstem can result in cranial nerve
      deficiencies. As the development of tooth germ is dependent on n. trigeminus,
      which originates from the brainstem, the hypothesis underlying this study was
      that anomalies of the brainstem would lead to an increased prevalence of tooth
      agenesis. Twenty-three patients (13 F and 10 M, age range 6-37 years) were
      studied, all with myclomeningocele and brainstem anomalies (Chiari II). They were
      examined retrospectively from the data in journals and dental radiographs and
      compared to available data on the prevalence of tooth agenesis in the Swedish
      population. Our hypothesis was rejected, since there was insignificant difference
      in the frequency of agenesis in our material (8.7%) compared with that of the
      Swedish population (7.4%).

PMID- 12512883
TI  - Mandibular movement capacity in 19-year-olds with and without articulatory speech
      disorders.
AB  - Associations between articulatory speech disorders and mandibular movement
      capacity, as well as between malocclusions and jaw movements, were examined in
      two groups of adolescents, i.e. 52 individuals with and 45 without
      misarticulations of speech. The mean age of the whole sample was 19.2 years.
      Articulatory speech disorders and functioning of the speech articulators were
      diagnosed by a phoniatrician. Mandibular movement capacity, malocclusions,
      occlusal interferences, and signs of temporomandibular dysfunction were recorded
      by an orthodontist. Multiple regression analyses showed that subjects with
      articulatory speech disorders were likely to have smaller opening capacity than
      subjects with a correct speech articulation. Excessive overjet, lateral cross
      bite, and a tendency to anterior open bite were associated with large movements
      of the jaw. These results suggest that in young adulthood mandibular movement
      capacity seems to vary depending on occlusion and is related to misarticulations
      of speech.

PMID- 12512884
TI  - Number of teeth, body mass index, and dental anxiety in middle-aged Swedish
      women.
AB  - Risk factors for poor dental health include obesity, low socio-economic status,
      poor dietary habits, and dental anxiety. The aim of this study was to explore the
      complex relation between body mass index (BMI) and number of teeth in middle-aged
      women taking education, dietary intake patterns, dental care utilization, and
      dental anxiety into account. Three groups of women (37-60 years): reference women
      (group I, BMI 23.8 +/- 3.1 kg/m2), obese women (group II, BMI 35.0 +/- 2.6
      kg/m2), and severely obese women (group III, BMI 41.0 +/- 3.4 kg/m2) were
      included. Questionnaires were used to assess education, smoking, number of teeth,
      dental care utilization, dental anxiety, dietary intake, and meal patterns. Age,
      education, and smoking habits did not differ significantly between groups.
      However, there were significant global differences in number of teeth (27.2 +/-
      3.4, 23.0 +/- 9.2, 24.7 +/- 5.9) and reported daily energy intake (9756 +/- 3363
      kJ, 10344 +/- 3850 kJ, 11970 +/- 3786 kJ in groups I, II, and m, respectively).
      In a multiple regression model, a lower number of teeth was independently
      associated with higher age, higher BMI, lower education, irregular dental care,
      high dental anxiety, higher energy intake, and lower iron intake. These variables
      explained 25% of the variation in number of teeth. In conclusion, BMI is an
      independent predictor of number of teeth in middle-aged women when socio
      economic, dietary, and psychological factors are taken into account.

PMID- 12512885
TI  - Social and behavioral correlates of oral quality of life studied among university
      students in Tanzania.
AB  - This study applies an abbreviated version of the Oral Impacts on Daily
      Performances (OIDP) and the Life Satisfaction scale to oral-health-related
      quality of life (OHRQOL) and quality of life (QOL) among Tanzanian university
      students. The following questions were addressed: Are social and behavioral
      status associated with overall OIDP frequency scores? Do social and behavioral
      variables contribute to the explainable variance of the OIDP frequency scores
      beyond the effect of clinical indicators of oral disorders? Do OIDP frequency
      scores influence general QOL as measured by the Life Satisfaction scale? A two
      wave cross-sectional study was conducted during the summer of 1999, involving 19
      45-year-old students at the University of Dar es Salaam. One-thousand-one-hundred
      and-twenty-three students completed self-administered questionnaires and 228
      respondents were re-examined clinically after 4 weeks. The rates of tooth decay
      and tooth loss were 34% and 37%, respectively. Medical-non-medical status (OR =
      2.7) self-perceived health status (OR = 2.7), and sugar avoidance (OR = 2.2)
      varied systematically with OIDP scores in multivariate analyses. Tooth decay and
      tooth loss alone contributed 10% to the explainable variance in the OIDP scores.
      Entering social and behavioral variables increased the explainable variance to
      19%. Finally, life-satisfaction scores varied systematically and positively with
      the OIDP frequency scores in bi- and multivariate analyses. This study gives some
      indications that the social and behavioral contexts of Tanzanian university
      students are important in shaping their responses to oral disorders.

PMID- 12512886
TI  - Occlusal caries detection and quantification by DIAGNOdent and Electronic Caries
      Monitor: in vitro comparison.
AB  - The Electronic Caries Monitor (ECM) and the recently introduced laser-based KaVo
      DIAGNOdent have been developed as clinical diagnostic aids in the detection and
      quantification of occlusal carious lesions. The aim of this in vitro study was to
      compare their reproducibility and validity. The ability of DIAGNOdent to retrieve
      sites of occlusal carious lesions without reference to photographs or drawings
      from previous assessments was also tested. The material comprised 87 premolar
      teeth: the occlusal surfaces were sound or exhibited non-cavity carious lesions
      of varying severity. All were photographed and measured by DIAGNOdent and ECM on
      2 occasions, 2 weeks apart. The teeth were then sectioned into 300 microm thick
      slices. Two observers independently classified the sections according to the
      histopathology, into 5 categories, ranging from sound to dentinal caries in the
      inner part of the dentin. Statistical analysis comprised intra-class correlation
      coefficients (ICC) to test reproducibility and regression analysis of validity.
      Sensitivity and specificity were also calculated for detection of D3 lesions for
      both devices. DIAGNOdent recorded maximum readings at identical sites on both
      occasions in 89% of the teeth. The ICC for readings on 2 separate occasions was
      0.97 for DIAGNOdent and 0.71 for ECM. The correlations with histology were r =
      0.93 and 0.83, for DIAGNOdent and ECM, respectively. For detection of D3 lesions,
      the sensitivity and specificity were 0.8 and 1 for DIAGNOdent and 0.75 and 0.88
      for ECM. In this in vitro study, DIAGNOdent was superior to ECM for occlusal
      caries detection.

PMID- 12512887
TI  - Maximal bite force and its associations with spinal posture and craniofacial
      morphology in young adults.
AB  - Maximal bite force (MBF) and its associations with craniofacial morphology and
      spinal posture were studied in a group of young adults (46 M and 38 F) aged 21 to
      23 years. MBF was recorded in molar and incisal regions. Sagittal spinal posture
      was measured by spinal pantography and trunk asymmetry at thoracic and lumbar
      levels by a forward-bending test. Craniofacial variables and posture of the
      cervical spine were examined from lateral cephalograms taken in a natural head
      position. No statistically significant correlations existed between MBF and
      spinal posture, but significant correlations did exist between MBF and
      craniofacial variables, especially in women.

PMID- 12512888
TI  - Effect of a novel ceramic filling material on plaque formation and marginal
      gingiva.
AB  - The aim of this clinical investigation was to evaluate a novel ceramic (CF)
      filling material (DoxaDent) compared to resin composite (RC) and enamel in regard
      to plaque formation and gingival inflammation. The CF material is inorganic, non
      metallic, and contains calcium aluminate, silicate, and water. To make intra
      individual comparisons possible, each participant had at least one set of three
      test surfaces: two Class V restorations with subgingival cervical margins (one of
      the novel CF material and one of a hybrid RC) and one non-filled enamel surface
      (E). The amounts of plaque, gingival crevicular fluid, and clinical signs of
      gingival inflammation were intra-individually compared in 20 sets of the three
      test surfaces. In a cross-sectional study (CSS), the effect of oral hygiene on
      plaque formation and gingivitis around the surfaces was evaluated. In a following
      10-day experimental gingivitis study (EGS), plaque formation and the induction of
      gingivitis during refrain from oral hygiene was compared. In the CSS, no
      significant differences were found between the surfaces in terms of amount of
      plaque and degree of gingival inflammation. At the end of the EGS the restorative
      materials showed a significantly higher amount of plaque (CF versus E, P = 0.014;
      RC versus E, P = 0.034), but no significant differences were found in degree of
      gingival inflammation. In condusion, the ceramic filling material was comparable
      to RC regarding plaque formation and gingival inflammation with customary oral
      hygiene. With neglected oral hygiene, significantly less plaque growth and a non
      significant tendency toward lower amounts of gingival crevicular fluid were
      observed on enamel surfaces.

PMID- 12512889
TI  - Accuracy of fine-needle aspiration biopsy for Warthin's tumours.
AB  - BACKGROUND: Although the overall accuracy of fine-needle aspiration biopsy (FNAB)
      for salivary gland neoplasms has been well established, definitive results for
      Warthin's tumour (WT) are lacking. For most salivary gland tumours, surgery is
      recommended because of progressive enlargement and the risk of malignant
      transformation. This behaviour is unusual with WT, and surgery is usually
      advocated for pathologic confirmation. A highly accurate diagnosis of WT by FNAB
      may justify conservative management for the asymptomatic patient. However, if the
      reliability of this diagnostic procedure is questionable, there should be little
      hesitation in recommending parotidectomy. METHODS: A retrospective study design
      was used to evaluate the accuracy of FNAB for parotid WTs. All consecutive
      parotid FNABs and parotidectomy specimens from 1992 to 2000 were reviewed, and
      cases suggestive of WT were identified. The fine-needle cytology and
      histopathology results were then correlated. The true-positive, false-positive,
      and false-negative rates were tabulated to determine the sensitivity and positive
      predictive value (PPV) of FNAB for WT. RESULTS: A total of 41 patients were
      included in the study. Of these, 33 patients had FNABs suggestive or diagnostic
      of WT that were confirmed following parotidectomy (true positives = 33). In 4
      patients, the FNAB incorrectly suggested WT, with the surgical histopathology
      confirming different diagnoses (false positives = 4) (3 acinic cell carcinomas
      and 1 pleomorphic adenoma). Four patients had surgically confirmed WTs with FNABs
      suggestive of other diagnoses (false negatives = 4) (1 cystic squamous cell
      carcinoma, 1 simple cyst, 1 "inflammatory process," and 1 "negative for malignant
      cells"). The sensitivity and PPV were 89.2% and 89.2%, respectively. CONCLUSION:
      Although the sensitivity and PPV in this study are high, the false-positive rate
      is clinically significant given the type of lesions missed. Three acinic cell
      carcinomas and one pleomorphic adenoma were misdiagnosed as WT on FNAB. One must
      be cautious in recommending conservative management for parotid tumours even when
      a WT is suggested by FNAB.

PMID- 12512890
TI  - Control of bleeding in endoscopic sinus surgery: use of a novel gelatin-based
      hemostatic agent.
AB  - OBJECTIVE: To determine whether FloSeal Matrix Hemostatic Sealant is a safe and
      effective means of controlling bleeding post-endoscopic sinus surgery (ESS) and
      to assess postoperative healing. DESIGN: Prospective clinical study. SETTING:
      University of Toronto. METHODS: Eighteen patients with FloSeal placed on a total
      of 30 operative sites post-ESS. Time to cessation of bleeding was assessed
      intraoperatively. Patients had the operative sites assessed at 30 days
      postoperatively. MAIN OUTCOME MEASURES: Effectiveness of FloSeal in controlling
      bleeding and aiding in healing of the operative site. RESULTS: FloSeal adequately
      controls postoperative bleeding in patients post-ESS. Healing was also not
      adversely affected. CONCLUSIONS: FloSeal is a safe and effective treatment for
      controlling blood loss after EES. It may also provide support to the middle
      meatus as well as improve healing of the operative site compared with the use of
      traditional nasal packing. However, randomized clinical trials are needed to
      further evaluate this.

PMID- 12512891
TI  - Mucosal wave asymmetries in the clinical voice laboratory.
AB  - OBJECTIVE: Anecdotally, it has been observed that in some healthy middle-aged
      men, who have neither vocal complaints nor known vocal pathology, asymmetries of
      the mucosal wave exist when examined videostroboscopically. This may cause
      concern on the part of the otolaryngologist, who might consider mucosal wave
      asymmetries to be a forewarning of subclinical pathology and subject the patient
      to unnecessary, expensive, and anxiety-provoking investigations or interventions.
      The purpose of this study is to establish the presence of mucosal wave
      asymmetries in a healthy, asymptomatic subpopulation. Acoustic spectral analysis
      is also used to determine if the presence of subharmonics might be associated.
      STUDY DESIGN: A prospective, cohort study design was used. The population was
      randomly selected, healthy, asymptomatic, nonsmoking men aged 35 to 50 years.
      Each subject completed acoustic spectral analysis and a medical questionnaire,
      followed by videostroboscopic laryngeal examination. RESULTS: Thirty-seven
      percent of the subjects exhibited mucosal wave variations at stroboscopy,
      characterized as periodic lateral phase asymmetries. There was no association
      with the acoustic spectral parameters chosen. CONCLUSION: Mucosal wave
      asymmetries may be a variance of normal. The 37% found here is expected to be
      very significant. Mucosal wave asymmetries are likely to be far more common in
      the general population than previously believed. There have been few normative
      data published for variations of the mucosal wave specifically for epidemiologic
      purposes. These results establish a starting point and justification for the
      normative population studies under way at our institution. Clinically, in the
      absence of such data, otolaryngologists may overinterpret videostroboscopic
      findings, leading to unnecessary investigations or interventions.

PMID- 12512892
TI  - Overview of the radiology, histology, and bone morphogenetic protein expression
      during distraction osteogenesis of the mandible.
AB  - INTRODUCTION: Distraction osteogenesis (DO) is a form of in vivo tissue
      engineering during which an osteotomy and controlled distraction are used to
      lengthen bone. The molecular signals that govern distraction-induced bone
      formation have not been fully elucidated. Specifically, the role of bone
      morphogenetic proteins (BMPs) in DO of the mandible remains unclear. OBJECTIVE:
      To characterize the radiologic and histologic evolution of newly formed bone
      during DO of the mandible and to relate these changes to the expression of BMPs.
      METHODS: Fourteen skeletally mature male rabbits were used. A distractor device
      was surgically applied to one side of the mandible following osteotomy. After 1
      week (latency period), distraction was started at a rate of 0.25 mm every 12
      hours for 3 weeks (distraction period) and was followed by a 3-week consolidation
      period. Two animals were sacrificed each week after surgery (weeks 1 to 7). The
      mandible was resected and the new bone assessed by radiography and histology. The
      expression of BMPs was also analyzed using immunohistochemistry. RESULTS: There
      was radiographic and histologic evidence of bone formation during the distraction
      period. By week 6, there was mature woven bone within the distraction zone. Bone
      morphogenetic proteins 2 and 4 were strongly expressed in osteoblasts during
      distraction and in chondrocytes during consolidation. The expression of BMP-7 was
      relatively minor. CONCLUSION: The temporal and spatial pattern of BMP expression
      suggests that these proteins are important mediators of mandibular DO.
      Understanding the expression of BMPs may facilitate the use of recombinant
      proteins to enhance the rate and quality of bone generation during craniofacial
      DO.

PMID- 12512893
TI  - Randomized evaluation of the audiologic outcome of ventilation tube insertion for
      middle ear effusion in patients with nasopharyngeal carcinoma.
AB  - OBJECTIVE: Complications after ventilation tube insertion for middle ear effusion
      in patients with nasopharyngeal carcinoma are frequent. This may compromise the
      overall benefit obtained from the procedure. This study evaluates the hearing
      improvement after tube insertion compared with observation alone to see if the
      benefits of the procedure outweigh its potential complications. DESIGN:
      Prospective randomized controlled trial. SETTING: Full clinical and emergency
      otolaryngologic services hospital in an academic institution. METHODS: Patients
      with nasopharyngeal carcinoma and middle ear effusion were randomized for
      preradiotherapy ventilation tube insertion or observation. Audiologic assessment
      with a pure-tone audiogram was performed before the procedure, after ventilation
      tube insertion, and at fixed intervals after irradiation. Audiologic outcome was
      compared between the two groups. MAIN OUTCOME MEASURE: Air-conduction threshold
      and air-bone gap on a pure-tone audiogram at different intervals after
      radiotherapy. RESULTS: There was no significant difference in hearing threshold
      changes between the two groups for up to 4 years. Both groups had air-bone gap
      improvement following radiotherapy and the improvement was not significantly
      different between the two groups. The proportion of patients with closure of the
      air-bone gap on follow-up was not different between the two groups. CONCLUSIONS:
      Ventilation tube insertion before radiotherapy did not offer additional hearing
      benefit when compared with observation alone. The procedure had no deleterious
      effect on hearing for up to 4 years.

PMID- 12512894
TI  - Experimentally induced rhinosinusitis in rabbits.
AB  - OBJECTIVE: The purpose of this study was to develop an experimental
      rhinosinusitis model by using bacteria-added absorbable material for temporary
      ostial obstruction. METHOD: Absorbable gelatin sponge was inserted between the
      endoturbinals and the ostium of the sinus. In the first group, the effects of
      surgical procedure and Gelfoam on ostial mucosa were examined macroscopically. In
      the second group Gelfoam was moistened with Staphylococcus aureus (ATCC 25923).
      The sinuses of rabbits were examined by coronal com puted tomography before each
      surgical procedure and sacrifice. The animals were sacrificed at the first,
      second, fourth eighth, and tenth weeks. Histologic and microbiologic examinations
      were performed. RESULTS: In the first group, fibrotic bands and adhesions were
      observed between the ostium of the maxillary sinus and the endoturbinals in the
      first and second week. In the second group, a thick purulent discharge that
      invariably filled the sinuses of the inoculated side was seen after the first
      week of induction, and opacity, which was determined radiologically, did not
      disappear until the end of the study. CONCLUSION: In this study, an experimental
      rhinosinusitis model was accomplished. It is currently believed that obstruction
      of the ostium with mucosal edema, polyps, or tumour leads to maxillary sinusitis.
      In this model, the pathogenesis of human sinusitis was imitated by temporary
      occlusion of the ostium with bacteria-added Gelfoam. This model can be used in
      further studies to explore the role of the ostium in the pathogenesis of
      sinusitis.

PMID- 12512895
TI  - Value of minor salivary gland biopsy in diagnosing Sjogren's syndrome.
AB  - OBJECTIVE: Minor salivary gland biopsy is suggested for diagnosing Sjogren's
      syndrome in patients with clinical signs of sicca syndrome. This biopsy is mainly
      examined on the basis of the semiquantitative morphologic criteria without taking
      into account the detection of characteristic myoepithelial sialadenitis (MESA).
      DESIGN: The role of minor salivary gland biopsy in the diagnosis of Sjogren's
      syndrome as a possible detection method for MESA was examined in a retrospective
      study. METHODS: Minor salivary gland biopsies were obtained from 32 patients
      between 1986 and 1996. Twenty-two patients fulfilled the criteria for primary and
      10 patients for secondary Sjogren's syndrome based on the catalogue of the
      European Study Group on Diagnostic Criteria for Sjogren's Syndrome. The
      histopathologic assessment was based on the histomorphologic MESA criteria, that
      is, parenchymatrophy, interstitial lymphocytic cell infiltration, and
      myoepithelial cell islands. RESULTS: The histopathologic assessment revealed
      normal minor salivary glands in 37.5% of the cases and chronic sialadenitis in
      59.4% of the patients. Only one female patient (3.1%) had changes characteristic
      of MESA. CONCLUSION: Minor salivary gland biospy is therefore an unsuitable
      method for detecting MESA if the pathomorphologic correlative of MESA is used to
      confirm the diagnosis of Sjogren's syndrome.

PMID- 12512896
TI  - Cochlear delivery of fibroblast growth factor 1 and its effects on apoptosis and
      cell cycling in noise-exposed guinea pig ears.
AB  - OBJECTIVES: Acidic fibroblast growth factor 1 (FGF-1) is a mitogen and
      antiapoptotic factor synthesized by cochlear neurons and transported to the organ
      of Corti. The objectives of this investigation were threefold: (1) to develop an
      animal model to study the cochlear effects of intratympanic delivery of FGF-1;
      (2) to determine the distribution, in the mature mammalian cochlea, of FGF-1 and
      the receptor, FGFR3, to which it binds with high affinity; and (3) to examine the
      effect of exogenous FGF-1 on cochlear apoptotic and cell-cycling markers in noise
      and non-noise-exposed guinea pigs ears. METHODS: Fifteen adult Hartley guinea
      pigs were divided into three groups. Group 1 animals (n = 5) underwent direct
      placement of FGF-1 in phosphate buffered saline (PBS) (20 pg/mL) soaked Gelfoam
      pledgets to the right round window membrane. Phosphate buffered saline-soaked
      Gelfoam pledgets were placed on the left round window membrane as a control. In
      group 2 animals (n = 5), surgical placement of either FGF-1 or PBS was followed
      by exposure to 120 dB of white noise for 2 hours. Group 3 animals (n = 5) were
      subjected to identical noise conditions prior to undergoing round window
      application of either FGF-1 or PBS. All groups were allowed to recover in a noise
      controlled environment for 12 hours following surgery. Anti-FGF-1-stained Western
      blots and optical densitometry analyses were used to quantitate passage of FGF-1
      into cochlear perilymph. Standard in situ immunohistochemical techniques were
      used to stain each cochlea for FGF-1 and FGFR3, apoptotic markers p53 and p21,
      Bcl-2, and the cell-cycling marker proliferating cell nuclear antigen (PCNA).
      Tissue sections were subjected to the terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end-labelling technique (TUNEL) for
      apoptosis. RESULTS: Western blot and optical densitometry analyses of cochlear
      perilymph showed increased concentrations of FGF-1 in 10 of 14 experimental
      cochleas. Cochlear perilymph FGF-1 was consistently bound to heparan sulphate
      proteoglycan (HSPG). Immunoreactivity of both FGF-1 and FGFR3 was observed in
      spiral ganglion neurons, inner and outer hair cells, pillar cells, and Dieter and
      Hensen's cells. Specific FGF-1 immunostaining to the distal portion of the pars
      pectinata of the basilar membrane was noted in noise-exposed animals only. Bcl-2
      and PCNA immunostaining was not detected in any group. There was no significant
      nuclear immunoreactivity to proapoptotic markers, p53 and p21, in any group.
      Semiquantitative analysis of TUNEL staining in block sections of all cochleas
      demonstrated a 340% increase in nuclear immunoreactivity of noise-exposed outer
      hair cells and organ of Corti cells. There was no difference between FGF-1
      treated and control ears subjected to TUNEL staining. CONCLUSIONS: Exogenous FGF
      1 crosses the round window membrane and is bound to HSPG in cochlear perilymph.
      The specific immunoreactivity of the pars pectinata to FGF-1 may represent a
      unique reservoir for cochlear FGF-1 in noise-exposed ears of the guinea pig.
      Noise induces apoptosis of organ of Corti cells as demonstrated with the TUNEL
      technique. PCNA, Bcl-2, p53, and p21 in noise-exposed and non-noise-exposed
      guinea pig cochleas are not affected by exogenous FGF-1. Noise-induced hair cell
      apoptosis appears to be independent of the p53 pathway. Lack of immunoreactivity
      to Bcl-2 supports the concept that the apoptotic mechanism is likely to involve C
      Jun-N-terminal kinase- or caspase-dependent pathways. Exogenous FGF-1 does not
      alter apoptosis or cell cycling in the mature guinea pig cochlea within 12 hours
      of acute acoustic trauma.

PMID- 12512897
TI  - New parameter of hemoglobin status as an indicator of efficacy of preoperative
      angioembolization in extracranial hypervascular tumours.
AB  - BACKGROUND: Routinely, the standard for measuring the success of preoperative
      embolization procedure as an adjunct in the management of head and neck vascular
      tumours has been to evaluate the amount of blood loss, duration of surgery, and
      intraoperative neurovascular injuries. OBJECTIVE: We hypothesized that the rate
      of change in the preoperative hemoglobin status would more accurately and
      objectively reflect the effectiveness of the embolization technique. MATERIALS
      AND METHODS: Twenty-six patients with extracranial vascular tumours were divided
      into two groups (A and B) of 13. Group A patients had preoperative embolization
      and group B patients directly underwent surgery. The difference between the
      preoperative and postoperative hemoglobin levels and the percentage rate of
      change of hemoglobin status were calculated. RESULTS: The percentage rate of
      change of preoperative to postoperative hemoglobin is less in group A (9.43%)
      when compared with group B (18.27%). The ratio of preoperative to postoperative
      hemoglobin in the two groups is also statistically significant (1:1.9).
      CONCLUSIONS: The percentage rate of change of preoperative to postoperative
      hemoglobin and the ratio of preoperative to postoperative hemoglobin are more
      accurate and objective parameters for assessment of success of preoperative
      embolizations rather than other variables such as intraoperative blood loss or
      duration of surgery.

PMID- 12512898
TI  - Minnesota Multiphasic Personality Inventory profile of patients with subjective
      tinnitus.
AB  - Subjective tinnitus is frequently seen in the general population. We investigated
      the personality traits in tinnitus and nontinnitus groups, both of which were
      nonpsychiatric. In this study, we evaluated 28 patients with subjective tinnitus
      and 28 subjects for a control group. In the analysis of psychiatric status,
      Minnesota Multiphasic Personality Inventory (MMPI) profiles were used.
      Psychasthenia was found to be higher in tinnitus patients of both sexes, whereas
      Hypochondriasis, Hysteria, Masculinity/Feminity, Psychasthenia, Schizophrenia,
      and Social Introversion scores were higher in females with tinnitus. In our
      research, it is thought that the experience of tinnitus may cause the
      psychological disturbance.

PMID- 12512899
TI  - Endoscopic repair of a nasal septal perforation.
AB  - The repair of septal perforations represents a challenging problem, with numerous
      techniques existing to address the defect. The use of sinonasal endoscopy
      represents a novel approach to solving this problem. By using the endoscope,
      excellent visualization and exposure can be achieved without excessive
      dissection. In addition, the use of the camera and monitor allows for excellent
      teaching capabilities.

PMID- 12512900
TI  - Myxoid liposarcoma of the tongue.

PMID- 12512901
TI  - Idiopathic pachymeningitis: a nonspecific relapsing inflammatory intracranial
      lesion presenting as multiple cranial nerve palsies.

PMID- 12512902
TI  - Epstein-Barr virus-mild acquired immune deficiency syndrome (EBV-MAIDS) in
      postsurgical sinusitis.
AB  - BACKGROUND: Functional endoscopic sinus surgery has remarkably improved the
      treatment of chronic rhinosinusitis patients. Computed tomography, endoscopic
      optical instrumentation, powered microdebriders, and computer-assisted surgery
      have surmounted the technical problems of obstructive sinusitis care. Most
      experienced practitioners achieve reported success rates of 85-95% among their
      surgical patients. However, the 5-15% refractory patients reported by all
      rhinologic surgeons leave an exasperating and perplexing group who, despite
      appropriate mechanical corrections, continue to experience debilitating
      rhinosinusitis episodes requiring repeated oral, nebulized, or intravenous
      antibiotics, and in some cases, antifungal therapy. METHODS: Recent studies have
      indicated that host immune response mechanisms may be altered in the paranasal
      sinus tissues of sinusitis patients. After years of observation, it was felt that
      these difficult patients may suffer from a common thread of significant partial
      immunocompromise. Drawing on military experience of treating immunoimmature
      populations prone to Epstein-Barr virus (EBV) infectious mononucleosis and the
      consequent postmononucleosis syndrome, it was sought to screen disabled
      refractory postsurgical sinusitis patients for this factor and treat them with
      long-standing military protocols for the immunoimmature populations dispatched to
      third-world combat conditions. RESULTS: Treatment of Epstein-Barr Virus-Mild
      Acquired Immune Deficiency Syndrome consisted of periodic intramuscular serum
      immune globulin injections (immunomodulator therapy), after obtaining their
      thorough written informed consent, which produced substantial and sustainable
      improvement in patient's quality of life. CONCLUSION: Detection of mild-to
      moderate acquired immune deficiency among postsurgical rhinosinusitis patients
      can lead to successful treatment and an improved quality of life.

PMID- 12512903
TI  - Yamik sinus catheter in the topical treatment of patients with acute
      rhinosinusitis after previous sinus surgery.
AB  - BACKGROUND: The Yamik sinus catheter was designed as a new device for the topical
      treatment of rhinosinusitis. It creates intermittent positive and negative
      intranasal pressure after sealing the ipsilateral nostril and choana with two
      inflatable cuffs. Affecting the nasal cavity and all paranasal sinuses of one
      side at a time, it is used to evacuate mucous and secretions as well as and to
      introduce antiseptic, antibacterial, or antifungal solutions. METHODS: This study
      was designed to evaluate the effectiveness of the Yamik catheter in cases of
      acute purulent rhinosinusitis in patients who previously underwent endonasal
      sinus surgery for chronic rhinosinusitis. Twenty patients were treated at
      repeated visits to the outpatient clinic of our institution. At each visit, their
      clinical symptoms as well as findings on anterior rhinoscopy, nasal endoscopy,
      and A-mode ultrasound were evaluated. RESULTS: Acute disease resolved completely
      within 10 days of treatment in 17 of the 20 patients. Two patients discontinued
      treatment after repeated visits, showing only mild improvement. One patient felt
      uncomfortable during the application of the Yamik catheter and did not continue
      after the initial treatment. CONCLUSION: Our results suggest that the Yamik
      catheter may be a helpful device in the topical treatment of acute rhinosinusitis
      and it appears possibly helpful in patients who suffer from episodes of acute
      purulent infection after previous sinus surgery.

PMID- 12512904
TI  - A retrospective analysis of treatment outcomes and time to relapse after
      intensive medical treatment for chronic sinusitis.
AB  - BACKGROUND: Despite the high prevalence of chronic sinusitis, there are few
      published studies assessing its response to medical treatment. We analyzed,
      retrospectively, 40 patients seen in our center who were treated for chronic
      sinusitis with a protocol of intensive medical therapy. Both symptomatic and
      radiographic improvements were assessed as well as factors associated with early
      relapse. METHODS: Intensive medical treatment consisted of 1 month of
      antibiotics, a short course of oral steroids, and adjunctive therapy (e.g., nasal
      irrigations plus intranasal steroids). After intensive medical therapy,
      adjunctive medical therapy was continued. A sinus computed tomography was
      performed at baseline and 6-8 weeks later and scored for extent of disease. Pre-
      and posttreatment symptom scores also were assessed. Time to relapse was defined
      as the time interval after antibiotic treatment at which a recurrence of symptoms
      necessitated reinstitution of antibiotics and/or oral steroids. RESULTS: Thirty
      six of the 40 patients improved either symptomatically, radiographically, or both
      following the medical regimen. Twenty-six patients had sustained symptomatic
      benefit beyond 8 weeks after initial treatment. A statistically significant
      correlation was found between the change in pre- to posttreatment symptom scores
      and computed tomography scores. Using a log-rank test to compare rates of
      sinusitis relapse, nasal polyposis and a history of sinus surgery were
      significantly associated with earlier relapse (p = 0.006 and 0.018,
      respectively). In contrast, atopy, asthma, and persistent obstruction of the
      ostiomeatal unit were not associated with early relapse. CONCLUSION: Intensive
      medical treatment resulted in symptomatic and radiographic improvement in chronic
      sinusitis, and the majority of patients remained free of a relapse for >8 weeks.
      A history of nasal polyposis or previous sinus surgery was associated with
      earlier relapse of sinusitis symptoms. In contrast, the presence of atopy, a
      history of asthma, or persistent OMU obstruction was not associated with earlier
      relapse. Although long-term benefits have not been established, a prospective
      study of treatment outcomes from intensive medical treatment appears to be
      warranted.

PMID- 12512905
TI  - Significance of eosinophilia in chronic rhinosinusitis.
AB  - BACKGROUND: The purpose of this study was to investigate the impact of serum
      eosinophilia in the prognosis of chronic rhinosinusitis (CRS). Eosinophils are
      now considered to play a major role in the pathogenesis of CRS. To date, no study
      has evaluated the clinical course of patients with CRS and serum eosinophilia.
      METHODS: A retrospective chart review of 620 patients who underwent endoscopic
      sinus surgery, (ESS) for CRS was performed. Thirty-one patients (5%) had elevated
      serum eosinophil counts and served as the study group. Patient charts of the
      study group and 34 (5%) controls with normal serum eosinophil counts were
      reviewed for comorbid diseases including asthma, polyps, and allergic fungal
      sinusitis. The number of ESSs performed and the postoperative recurrence of
      multiple sinus infections and need for antibiotics, systemic steroids, and
      antifungal agents were compared. RESULTS: A higher proportion of patients with
      serum eosinophilia had a history of asthma, polyp disease, and allergic fungal
      sinusitis. Postoperatively, the study group had a statistically significant
      difference (p < 0.05) as compared with controls with respect to postoperative
      recurrent sinus infections (94% versus 32%) and polyp disease (35% versus 3%).
      Statistical difference between study and control groups was also found with
      respect to the postoperative need for antifungal agents (23% versus 3%), multiple
      courses of antibiotics (84% versus 32%), and revision ESS (84% versus 24%).
      Although not statistically significant, a higher proportion of the study group
      required systemic steroids. CONCLUSIONS: CRS patients with serum eosinophilia
      have a worse prognosis when compared with controls. Patients with eosinophilia
      should be counseled appropriately, and the physician should be aware of the
      chronicity of disease.

PMID- 12512906
TI  - Bacterial colonization of nasal steroid inhalers in chronic rhinosinusitis.
AB  - BACKGROUND: The aim of this study was to determine if nasal steroid inhalers
      harbor bacteria. METHODS: Nasal steroid inhalers were randomly selected from an
      adult patient population with chronic rhinosinusitis. Swab cultures of the tip of
      the nasal inhaler were obtained and submitted for microbiological analysis.
      Contemporaneous control cultures were obtained from freshly opened nasal steroid
      inhalers. Comparisons were conducted between bacterial recovery rates and types
      of organisms recovered from the patient and control groups. RESULTS: Among 31
      nasal inhalers in use, 14 inhalers (45%) were found to harbor bacteria. The most
      common organisms were coagulase negative Staphylococci (11 inhalers) followed by
      oral flora (2 inhalers) and bacillus species (1 inhaler). None of the 10 control
      cultures were found to harbor bacteria. Nasal steroid inhalers in use were more
      likely to have bacterial colonization than new inhalers (p = 0.008, chi-square).
      CONCLUSIONS: Nasal steroid inhalers may harbor pathogenic bacteria. Therefore,
      they may serve as a vehicle for subsequent reinfection.

PMID- 12512907
TI  - Allergic rhinitis and atopy in 18-year-old students.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence of allergic
      rhinitis and atopy in adolescents and whether air pollution in their schools
      contributed to allergic sensitization. METHODS: Analyses were performed in 1992
      1994 on 511 18-year-old students at four schools and on the indoor air and floor
      dust of their classrooms. The students underwent skin-prick tests (SPTs) and a
      nasal lavage and answered a computer-based questionnaire containing questions on
      allergy and nasal symptoms. RESULTS: Atopy, defined as at least one positive SPT
      response, was found among 37% of the students, with no difference between
      students of the four schools, regardless of whether the data were adjusted for
      gender, hereditary disposition to allergy, and smoking habits. The number of
      students who had positive SPT and reported nasal symptoms when exposed to
      possible allergens, which were found among 35%, did not differ between the
      schools. No correlation was found between the prevalence of atopic individuals
      and the levels of different indoor air pollutants in the schools. CONCLUSION: The
      prevalence of allergic rhinitis among adolescents is very high and suggests that
      it is, at least at the time of our study and in comparison with other studies,
      still increasing. Our results indicate that the indoor air and floor dust at the
      schools of the students do not contribute to allergic sensitization.

PMID- 12512908
TI  - Suppression of the Th2 pathway by suplatast tosilate in patients with perennial
      nasal allergies.
AB  - BACKGROUND: Suplatast tosilate (IPD-1151T), a selective Th2 cytokine inhibitor
      that suppresses the production of interleukin (IL)-4 and IL-5 in vitro or in
      animal models has been proved clinically effective for allergic rhinitis (AR).
      The aim of this study was to investigate changes in the Th2 pathway in human
      nasal mucosa after medication with IPD-1151T. Twelve patients were treated with
      IPD-1151T. METHODS: Twelve healthy volunteers served as normal controls. The
      following parameters were evaluated: (i) subjective nasal clinical symptoms, (ii)
      percentages of inflammatory cells (EG2, CD4, and CD8) by immunocytological
      staining, and (iii) levels of cytokines (IL-4, IL-5, IL-13, regulated on
      activation, normal T-cell expressed, and secreted [RANTES], and interferon [IFN]
      gamma) by enzyme-linked immunosorbent assay. RESULTS: Nasal symptom scores
      significantly decreased after treatment. With respect to cell infiltration, a
      significant decrease was observed in the percentage of inflammatory cells (EG2
      and CD4) and CD4/CD8 ratio. The levels of cytokines (IL-4, IL-5, IL-13, and IFN
      gamma) and the IL-5/IFN-gamma ratio were significantly decreased, and the IL
      4/IFN-gamma ratio became not significantly different from that in normal
      subjects. In contrast, RANTES did not change significantly. The percentage of
      reduction in IL-5 correlated with that in eosinophil infiltration, whereas that
      in RANTES did not. CONCLUSION: These results suggest that IPD-1151T can reduce
      the Th2 pathway.

PMID- 12512909
TI  - Complications of hydroxyapatite use for transnasal closure of cerebrospinal fluid
      leaks.
AB  - BACKGROUND: Hydroxyapatite cement (HAC) was first introduced in the 1980s as a
      new method for bone replacement. However, it has not been recommended for use in
      areas exposed to air. Despite this, surgeries have been performed using HAC to
      close nasal/sinus cerebrospinal fluid (CSF) leaks or in the treatment of
      encephaloceles. METHODS: This study retrospectively documented four patients in
      whom HAC was used for closure of ethmoid and sphenoid sinus CSF leaks. RESULTS:
      This study showed that exposed hydroxyapatite could be extremely problematic
      resulting in scarring, chronic granulation, infection, and prolonged healing.
      Oftentimes, revision surgery was necessary to help control the reaction to
      hydroxyapatite. CONCLUSION: Because of the frequent complications occurring with
      use of hydroxyapatite in the paranasal sinuses, its use should be limited to
      selected individuals in whom difficulty in achieving closure of the CFS leak
      could be anticipated and in whom adequate tissue coverage could be provided.

PMID- 12512910
TI  - The human vomeronasal organ: part IV. Incidence, topography, endoscopy, and
      ultrastructure of the nasopalatine recess, nasopalatine fossa, and vomeronasal
      organ.
AB  - BACKGROUND: Previous reports on the human vomeronasal organ (VNO) have been
      inconsistent. Observations of fossae on the nasal septum have been reported as
      the VNO. METHODS: Adult human subjects (210) and cadavers (31) were examined
      using rigid nasal endoscopy, serial histology, and biopsy ultrastructure (5).
      RESULTS: The nasopalatine fossa (NPF) and the nasopalatine recess (NPR) are
      discrete, but variable, structures located adjacent to the VNO region. The NPF is
      not a vomeronasal pit. A septal mucosal pit could hide the vomeronasal duct
      opening. The VNO is a submucosal structure located 2-8 mm superior to the NPR and
      cannot be positively identified either macroscopically or endoscopically.
      CONCLUSION: The VNO has long been mistaken for the NPF and septal mucosal pits.
      We show that serial histology is the correct method for identifying the VNO.

PMID- 12512911
TI  - Analysis of the adult chronic rhinosinusitis working definition.

PMID- 12512912
TI  - Dendritic cells highly quoted on immunotherapy stock market.

PMID- 12512914
TI  - Dendritic cell vaccines in the treatment of multiple myeloma: advances and
      limitations.
AB  - Dendritic cells (DCs) are antigen-presenting cells that play a key role in the
      induction of cytotoxic T-lymphocytes. Adjuvant immunotherapy with antigen-loaded
      DCs represents an attractive anticancer strategy for multiple myeloma (MM).
      Autologous DCs loaded with idiotypic protein or other myeloma-associated antigen
      have been used in several clinical trials. Preclinical and first clinical
      experience have provided valuable insights in the mechanisms of cellular
      immunity, but few, if any, patients with MM benefited from such vaccination.
      Taken together, the data suggest that antitumor T-cell responses fail in MM
      because of a deregulated cytokine network, downregulation of costimulatory
      surface receptor expression, and changes in T-cell repertoire, enabling tumor
      cells to escape immune effectors by preventing the antitumor immune response. We
      discuss current clinical protocols for DC-based immunotherapy in MM and review
      some strategies that may increase the efficacy of DC vaccines.

PMID- 12512913
TI  - Gene-modified dendritic cells for immunotherapy against cancer.
AB  - Dendritic cells (DCs) are described as professional antigen-presenting cells
      because of their superior T-cell stimulatory capacity. For this reason, attention
      is being focused on using DCs for clinical applications to treat cancer patients.
      Although preclinical studies are promising, the majority of clinical studies with
      DCs have not fulfilled the expectations, yet. The field of DC biology has
      progressed rapidly over the past years, leading to several options for the
      improvement of vaccination. Among the different parameters to investigate, this
      review focuses on the efficiency and biological and functional consequences of
      different gene transfer methods into different subsets of human DCs. Another
      important consideration for DC-based vaccination is the elucidation of the role
      of maturation and apoptosis during DC differentiation.

PMID- 12512915
TI  - Use of melphalan, thalidomide, and dexamethasone in treatment of refractory and
      relapsed multiple myeloma.
AB  - Twenty-one patients with relapsed and refractory Durie-Salmon stage III multiple
      myeloma who had either failed at least three previous regimens or presented with
      poor performance status, neutropenia, or thrombocytopenia were treated with up to
      four cycles of combination melphalan (50 mg intravenously), thalidomide (titrated
      to target of 400 mg orally daily), and dexamethasone (40 mg/day orally on d 1 to
      4) every 4-6 wk. Maintenance treatment consisting of daily thalidomide and
      monthly dexamethasone was continued until disease progression. Although generally
      tolerated, combination melphalan/thalidomide/dexamethasone produced grade 4
      neutropenia and thrombocytopenia in 52% and 38% of patients, respectively. Grade
      3 nonhematologic toxicities included fatigue (14% of patients),
      neuropathy/paresthesia (5%), and nausea (5%). Four patients died while on
      therapy: two from neutropenic complications and two from progressive disease.
      Melphalan/ thalidomide/dexamethasone was highly active in this poor prognosis
      population: Serum monoclonal protein reductions > or = 25% occurred in 14 (70%)
      of 20 evaluable patients, including 1 patient with a complete response and 2
      (13%) patients with reductions of 96%. Median progression-free-survival was 270 d
      (range: 73 to > 787 d) and median overall survival was 382 d. Median progression
      free survival (> 420 d) has not been reached among patients responding to
      melphalan/thalidomide/dexamethasone. These results show that
      melphalan/thalidomide/dexamethasone therapy is active and generally tolerated in
      heavily pretreated multiple myeloma patients whose prognosis is otherwise poor.

PMID- 12512916
TI  - Oral ftorafur plus intramuscular thiotepa as adjuvant chemotherapy in patients
      with breast cancer.
AB  - In this study, we evaluated the safety and efficacy of a combination of oral
      ftorafur administered together with intramuscular thiotepa as adjuvant
      chemotherapy for "early" breast cancer patients. A total of 30 patients with
      operated breast cancer were treated with 500 mg/m2 oral ftorafur for 10
      consecutive days plus 20 mg/m2 intramuscular (im) administered thiotepa on d 1
      and 8 every 28 d adjuvant chemotherapy. Eleven patients were premenopausal and 19
      were postmenopausal, with a median age of 53 yr. The total number of cycles
      delivered was 259 (median: 10 cycles per patient). Toxicity was low and usually
      consisted of leukopenia WHO grade I-II (14%) and neutropenia grade I-II (6%).
      Gastrointestinal toxicity was minimal. The 5-yr disease-free survival and overall
      survival were 55% and 84%, respectively. Relapse occurred as bone metastases
      (50%), local recurrence (25%), and liver (17%) and brain (8%) metastases. Our
      preliminary data showed that oral ftorafur and im thiotepa is a well-tolerated
      regimen and could be a useful alternative to the intravenous parenteral route as
      adjuvant treatment for early breast cancer. Randomized trials are needed to
      assess the possible advantage of this regimen over intravenous schedules.

PMID- 12512917
TI  - Predictive value of clinical features at initial presentation in pancreatic
      adenocarcinoma: a series of 308 cases.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in both men and
      women with a mortality incidence ratio of 0.99. In an effort to describe the role
      of clinical features at initial presentation, we conducted a retrospective
      observational study in patients with a biopsy-proven diagnosis of adenocarcinoma
      of the pancreas. Between 1986 and 2001, 308 patients (160 males, 148 females)
      were diagnosed with pancreatic adenocarcinoma. The mean age at diagnosis was 70.1
      yr (range: 34-96 yr). The mean survival was 7.6 mo (range: 0-97 mo). Statistical
      analysis was performed using log-rank tests and analysis of variance. As
      expected, age at diagnosis was a significant factor affecting survival, with
      older patients doing relatively poorly (p < 0.05). Patients with a good
      performance status performed significantly better than those with a poor
      performance status (p < 0.01). In addition, the presence of the tumor in the head
      of the pancreas was a predictor for improved survival (p < 0.01). Although
      smoking increased the chances of detection at an earlier age, neither diabetes
      mellitus nor a positive smoking history had a statistically significant effect on
      the survival. Pancreatic adenocarcinoma is a disease of the elderly associated
      with a poorer outcome. Knowledge of possible clinical predictors of survival may
      lead to better patient counseling regarding prognosis.

PMID- 12512918
TI  - Clinical significance of nm23 expression and chromosome 17 numerical aberrations
      in primary gastric cancer.
AB  - The metastasis suppressor gene nm23 located on chromosome 17 might be one of the
      targets in deletions of chromosome 17. In this study, we analyzed the expression
      of nm23 and chromosome 17 aberrations in gastric cancer and assessed their
      clinicopathological and prognostic significance. In 103 gastric cancer patients,
      we examined nm23 expression by immunohistochemistry and detected chromosome 17
      aberrations by fluorescence in situ hybridization. There was a significant
      difference in the expression of nm23 among differentiated histologic types (well
      > moderately > poorly) (p < 0.01). Negative expression of nm23 correlated with
      depth of invasion (p < 0.01), lymph node metastasis (p < 0.05), lymphatic
      invasion (p < 0.05), venous invasion (p < 0.05), poor prognosis (p < 0.05), and
      chromosome 17 loss (p < 0.05). Chromosome 17 aberrations broadly correlated with
      clinicopathological variables and were associated with poor prognosis (p < 0.05).
      Univariate analyses identified nm23 (p < 0.05), chromosome 17 aberrations (p <
      0.05), tumor size (p < 0.01), depth of invasion (p < 0.0001), lymph node
      metastasis (P < 0.001), hepatic metastasis (p < 0.01), peritoneal dissemination
      (p < 0.01), and lymphatic invasion (p < 0.01) as significant prognostic factors.
      Multivariate analysis showed that expression of nm23 and chromosome 17
      aberrations were not independent prognostic indicators. Our results indicate that
      negative expression of nm23 and chromosome 17 numerical aberrations correlate
      with tumor progression and poor prognosis but are not independent prognostic
      indicators.

PMID- 12512919
TI  - Biological and clinical significance of clonogenic assays in patients with
      myelodysplastic syndromes.
AB  - Biological and clinical significance of growth pattern of hematopoietic
      progenitors were investigated in 117 patients with primary myelodysplastic
      syndromes (MDSs) at referral. Abnormal (i.e., "leukemic" or absent) growth of GM
      colonies (CFU-GM) and GM clusters was found in 47% of patients with "advanced"
      MDS (RAEB, RAEB-t, and CMML) and in 15% of "low-risk" (RA/RARS) patients. In
      vitro erythropoiesis was decreased in most of the patients, with significantly
      lower number of BFU-E in "advanced" MDS than in RA/RARS patients. Megakaryocyte
      progenitors (CFU-MK) were very low or absent in almost all the patients,
      regardless of the FAB type. Significant correlation was demonstrated between the
      number of BFU-E and hemoglobin concentration and between number of CFU-MK and
      platelet count. Growth capacity of GM progenitors appears to be in proportion to
      "myeloproliferative" capacity of the malignant clone. T-cell depletion had no
      influence on growth capacity of hematopoietic progenitors, nor did colony growth
      respond in a dose-dependent manner to different concentrations of LCM. Growth
      capacity of MDS hematopoietic progenitors was independent of Bournemouth score,
      of the presence and type of cytogenetic abnormality, and of the expression of
      CD95 and caspase-3 antigens on bone marrow cells. However, in patients with
      "abnormal" growth of GM progenitors, CD34 antigen expression was significantly
      higher than in patients with "normal" growth. "Abnormal" GM growth was found to
      be independently predictive regarding the survival and the risk for AML
      development. In contrast, the prognostic value of erythroid and megakaryocyte
      cultures was found to be limited.

PMID- 12512920
TI  - Pharmacokinetics of oxaliplatin in humans.
AB  - Oxaliplatin is a novel platinum complex used for the treatment of metastatic
      colorectal carcinoma. The pharmacokinetics of the free fraction of oxaliplatin in
      blood were evaluated in 10 patients given 85 mg/m2 of oxaliplatin using an
      infusion time of 2 h. Blood samples were collected during and after the infusion
      and immediately placed on ice. The samples were ultrafiltrated centripetally and
      the concentration of oxaliplatin in the ultrafiltrate was determined by liquid
      chromatography in combination with postcolumn derivatization. The in vitro
      degradation rate was determined in blood from the patients taken immediately
      before drug administration. The maximal blood concentration (C(max)) and terminal
      half-life (t1/2) were 1.44 +/- 0.20 (SD) microg/mL and 14.1 min (range: 10.2
      24.5), respectively. The area under the blood concentration time curve (AUC),
      clearance (CL), and distribution volume (V(ss)) were (means +/- SD) 161 +/- 22
      microg min/mL, 32.1 +/- 4.2 L/h/m2, and 0.26 +/- 0.06 L/kg, respectively. There
      was a significant correlation between the clearance of oxaliplatin in the
      patients and the degradation rate in whole blood (r = 0.746; p = 0.017).
      Oxaliplatin has a short elimination half-life, which is in a sharp contrast to
      previously reported elimination half-lives obtained by analysis of the platinum
      content in plasma and ultrafiltrate. The correlation between in vivo and in vitro
      data suggests that the degradation in whole blood plays a role for the
      elimination of the drug.

PMID- 12512921
TI  - A study of bacteremia in febrile neutropenic patients at a tertiary-care hospital
      with special reference to anaerobes.
AB  - Patients with hematological malignancies who are receiving chemotherapy suffer
      prolonged periods of neutropenia, which leads to a greater risk of infection and
      mortality. A prospective study was conduced to determine the incidence of
      bacteremia in patients of hematological malignancies over a 2-yr period. A total
      of 119 episodes of febrile neutropenia occurred among 96 consecutive patients, of
      which 35 episodes were associated with bacteremia. Forty-four percent of the
      isolated bacteria were Gram-positive aerobes and 46% were Gram-negative aerobes.
      Staphylococcus aureus, Enterococcus spp., and Escherichia coli were the most
      common isolates. Gram-negative bacteremia was associated with a higher mortality.
      Anaerobes accounted for 4.4% of all isolates. The episodes of anaerobic
      bacteremia were polymicrobial and had a fatal outcome. A high incidence of
      antimicrobial resistance among aerobic and anaerobic bacteria was also recorded.
      Compared to previous years, a shift from a predominating Gram-negative to a Gram
      positive etiology was noted. The initial empiric antibiotic regimens should be
      based on a local knowledge of the most common causative microorganisms, their
      sensitivity pattern, and the outcome of bacteremia.

PMID- 12512922
TI  - Pancreatic metastasis and extrahepatic biliary obstruction in squamous cell lung
      carcinoma.
AB  - Primary lung cancer frequently metastasizes to distant organs. The pancreas is a
      relatively infrequent site of metastasis. As a result, extrahepatic bile duct
      obstruction (EHBDO) resulting from pancreatic metastasis from lung cancer is
      extremely rare and occurs mostly with small-cell lung cancer (SCLC). We report an
      unusual case in which a patient presented with jaundice and, after extensive
      workup, was diagnosed with squamous cell carcinoma of the lung with metastasis to
      the pancreas causing EHBDO. He underwent endoscopic retrograde
      cholangiopancreatography (ERCP) and the obstruction was relieved with a stent
      placement. The patient was treated with combination chemotherapy (carboplatin and
      paclitaxel) with a good clinical and radiographic response.

PMID- 12512923
TI  - Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody)
      treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic
      leukemia.
AB  - Alemtuzumab (Campath-1H) is a humanized CD52 monoclonal antibody that targets
      normal as well as malignant B- and T-lymphocytes. Alemtuzumab has significant
      antitumor activity in chronic lymphocytic leukemia (B-CLL) but also induces
      immunosuppression. We describe a case of fatal adenovirus infection in a heavily
      pretreated patient with fludarabine-refractory B-CLL receiving alemtuzumab
      therapy, drawing attention to the fact that also viruses other than
      cytomegalovirus (CMV) and herpes simplex (HSV) need to be considered in B-CLL
      patients with fever of unknown origin while on alemtuzumab treatment.

PMID- 12512924
TI  - Laparoscopic excision of large ovarian cysts.
AB  - OBJECTIVE: The aim of this study was to check the ability of operative
      laparoscopy to help in the management of large ovarian cysts that may reach above
      the level of the umbilicus. MATERIAL AND METHODS: Fifteen cases of large ovarian
      cysts reaching above the level of the umbilicus were chosen. Clinical and
      ultrasonic diagnosis denied any signs of malignancy. Pneumoperitoneum and a 5 mm
      trocar were inserted safely in the left midclavicular line below the ninth costal
      margin. This trocar allowed us to inspect the peritoneal cavity thoroughly.
      Another 5 mm trocar was inserted suprapubically in the contralateral side of the
      cyst and better inspection of the cyst and peritoneal cavity was then done. In
      the case of an apparently benign cyst, aspiration of the cyst fluid was done
      after puncturing its wall, then the cyst was removed as usual. RESULTS: In all of
      these cases, there was no laparoconversion and no other complications were
      recorded. Nine cases were mucinous and six were serous cystadenomas. The mean
      operation time was 53.66 +/- 14.7 min. CONCLUSION: Laparoscopic excision of large
      ovarian cysts is possible, and safe in suitable conditions, with immediate
      laparoconversion at hand at any time.

PMID- 12512925
TI  - Minimal stimulation protocol for use with intrauterine insemination in the
      treatment of infertility.
AB  - OBJECTIVE: To determine whether minimal stimulation with clomiphene and one
      injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy
      rates comparable with those in a conventional full hMG stimulation protocol for
      infertile patients undergoing intrauterine insemination (IUI). METHODS: A
      prospective study was carried out at the Infertility Clinic of a teaching
      institute and tertiary care referral center in Chandigarh, India. Two hundred
      couples with either unexplained infertility or ovulatory dysfunction cases who
      ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian
      stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate,
      medication and monitoring cost were compared between minimal and conventional
      stimulation protocols. RESULTS: There was no difference in the couples of the two
      stimulation protocols regarding their age, duration and type of infertility as
      well as cause of infertility. Number of ampoules of hMG and monitoring costs were
      significantly higher in the full hMG stimulation cases whereas pregnancy rate was
      comparable in both protocols. CONCLUSION: Minimal stimulation appears to be an
      effective protocol in cases of unexplained infertility undergoing intrauterine
      insemination. Reduced cost and minimal monitoring is appealing to patients and
      the clinician.

PMID- 12512926
TI  - Venous thromboembolic diseases associated with uterine myomas diagnosed before
      hysterectomy: a report of two cases.
AB  - Large uterine myomas (compressed veins in the pelvis), and the resulting impaired
      blood flow have been associated with deep vein thrombosis and pulmonary embolism.
      Careful detection of the preoperatively formed thrombi and strict perioperative
      management, such as in the following cases we report, may reduce lethal pulmonary
      embolism and may positively affect patient prognosis.

PMID- 12512927
TI  - Glucose screening test results in first and early third trimester of pregnancy:
      is there any correlation?
AB  - OBJECTIVE: This study aims to find correlation between glucose screening test
      (GST) results done in the first trimester and again in the early third trimester
      of pregnancy. METHODS: Analysis of the records of 458 cases of pregnant women
      (non-diabetic in early pregnancy as detected by glucose screening test and
      glucose tolerance test) between 22 and 35 years of age with a body mass index of
      less than 25 kg/m2 was done. These women underwent GST in the first trimester
      (GST-1) and again in the early third trimester (GST-2). When the GST-2 was 140
      mg% or above, a standard '3 hour glucose tolerance test' was done (GT TEST) with
      100 g of glucose. The GST was done by measuring the plasma glucose level 1 hour
      after taking 50 g of glucose, irrespective of food intake. RESULTS: A substantial
      correlation between the two groups of measurements was found. Based on the
      available data, a GST-1 value of 99 mg% or less was seldom associated with GST-2
      value of 140 mg% or more (GT TEST was positive in none). It was observed that
      100% of cases with GST-1 value of 140 mg% or more had GST-2 of 140 mg% or more.
      Out of those having GST-2 value of 140 mg% or more, 72% had GT TEST positive. In
      the intermediate group (i.e. those patients having GST-1 value of 100 mg%-139
      mg%), 51.7% had GST-2 values of 140 mg% or more. Out of these 51.7% cases, only
      23% cases turned out to be GT TEST positive. The correlation coefficients (CC)
      worked out to be 0.38 (substantial correlation for 0.20 < CC < 0.70). CONCLUSION:
      From the observations stated above, it is concluded that for women with GST-1 of
      99 mg% or less, a GST-2 is not necessary. For those having GST-1 of 140 mg% or
      more, a GT TEST is absolutely necessary instead of repeating the screening test
      again in the third trimester. But it is in the intermediate group (i.e. with GST
      1 value of 100 mg%-139 mg%) where the glucose screening test should be repeated
      in the early third trimester and GT TEST as and when necessary.

PMID- 12512928
TI  - A comparison of 100 microg oral misoprostol every 3 hours and 6 hours for labor
      induction: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy and safety of 100 microg oral misoprostol for
      induction of labor between the regimen of 3 hour and 6 hour interval
      administration. METHODS: Singleton pregnancies indicated for induction of labor
      between 34 and 42 weeks of gestation in the condition of unfavorable cervix
      (Bishop score < or = 4) and no contraindication for prostaglandins therapy were
      recruited into the study. All pregnant women were randomly assigned to receive
      100 microg oral misoprostol every 3 hours or 6 hours until the cervix was
      favorable for amniotomy, spontaneous rupture of membranes or active labor
      occurred. RESULTS: The mean time interval from induction to vaginal delivery was
      significantly shorter in the 3 hour interval group, compared with the 6 hour
      interval group (13.82 +/- 6.98h and 17.66 +/- 7.48h, P = 0.0019). There was no
      significant difference between the groups with regard to mode of delivery,
      analgesic requirement, maternal complication and neonatal outcome. CONCLUSIONS:
      100 microg oral misoprostol every 3 hours is more effective for labor induction
      than every 6 hours but there was no difference in mode of delivery, analgesic
      requirement, maternal complications and neonatal outcome. A dose of 100 microg
      misoprostol orally every 3 hours seems to be the optimum regimen and the new
      option for labor induction. However, further study should be performed.

PMID- 12512929
TI  - Mass treatment with nevirapine to prevent mother-to-child transmission of
      HIV/AIDS in sub-Saharan African countries.
AB  - OBJECTIVE: In 2001, an estimated 800000 children were newly infected with HIV,
      almost all through mother-to-child transmission (MCTC), and 90% of these children
      were born in Africa. In such resource-poor settings, cheaper and more easily
      administered antiretroviral drugs should be available for use. Mass treatment of
      an intrapartum and neonatal single dose of nevirapine regimen has been suggested
      as an effective strategy to prevent MCTC, yet this strategy has never been
      conducted in clinical trials. By discussing the advantages and disadvantages of
      it, we analyze the possibility of implementing this regimen. METHODS: We reviewed
      public health strategies to prevent MCTC in resource-poor settings, and discuss
      whether or not mass treatment of an intrapartum and neonatal single dose of
      nevirapine regimen can be recommended as one therapy in sub-Saharan Africa due to
      its simplicity of distribution and use, long-term efficacy, and cost
      effectiveness. RESULT: Recent studies in Uganda showed the high efficacy and cost
      effectiveness of a single dose of nevirapine only to HIV/AIDS-positive pregnant
      women. The characteristics of nevirapine also meet the requirements of mass
      treatment. Mass treatment of nevirapine would increase access to antiretroviral
      drugs among pregnant women because they can access nevirapine without volunteer
      counseling and testing, which 31% of pregnant women in developing countries
      refused to accept due to the fear of stigmatization. No serious adverse effects
      or drug resistance to this regimen were reported through the studies in Uganda.
      CONCLUSION: Mass treatment of a single-dose nevirapine can be recommended as one
      alternative therapy, and further research is recommended to obtain more
      information about the efficacy, side-effects, drug resistance, and compliance of
      this strategy.

PMID- 12512930
TI  - Cerebral blood flow distribution and hypoxic-ischemic brain damage in newborn
      rats.
AB  - OBJECTIVE: Our purpose was to assess the cerebral blood flow distribution and
      resulting grade of hypoxicischemic brain damage in newborn rats. METHODS: Seven
      day-old Wistar rats (n = 75) underwent left common carotid artery ligation
      followed by 2 hours hypoxia (8% oxygen in nitrogen) at 33 degrees C. The control
      animals were exposed to hypoxia without ligation (n = 8). Colored microspheres of
      15 microm in diameter were administered into the left cardiac ventricle
      percutaneously at the end of hypoxia. They were killed 24 hours after induced
      injury. Brain sections 2 mm in thickness were removed for microtubule-associated
      protein 2 (MAP-2) staining, and remaining parts were separated into left and
      right hemispheres for counting the microspheres. The blood flow distribution to
      the ligated side was expressed as the difference from the non-ligated control
      side. Severity of MAP-2 disappearance was ranked as normal, mild or severe.
      RESULTS: In the control rats, there was no loss of MAP-2 staining. The blood flow
      equally distributed into both cerebral hemispheres. The cerebral blood flow
      distribution on the side of carotid artery ligation decreased by 44.7 +/- 21.9%
      in the mildly damaged group and 65.8 +/- 16.8% in the severely damaged group.
      CONCLUSION: The greater the percentage difference of blood flow distribution from
      the non-ligated side, the more severe the brain damage.

PMID- 12512931
TI  - Juana Maria Pasquini: a role model for young neurochemists.

PMID- 12512932
TI  - Participation of women in neurochemistry societies.
AB  - Women have made important scientific contributions to the field of
      neurochemistry, and they have also been leaders in neurochemical societies
      throughout the world. Here I discuss women's involvement and leadership in six
      neurochemistry societies: American Society for Neurochemistry, Argentine Society
      for Neurochemistry, International Society for Neurochemistry, European Society
      for Neurochemistry, Japanese Society for Neurochemistry, and Asian-Pacific
      Society for Neurochemistry. The number of women who have been active in these
      societies and the level of their activity vary considerably. Neurochemical
      societies in the Western hemisphere, i.e., the American and the Argentine Society
      for Neurochemistry, have much greater numbers of women who have held office, been
      on council, or engaged in other leadership activities than in the rest of the
      world. The limited participation of women in the Japanese Neurochemistry Society
      relates to Japanese cultural views and was not unexpected. However, the
      relatively few women leaders in the International Society for Neurochemistry was
      a surprise. The European Society had a somewhat better record of female
      participation than did the International Society. The reasons for these
      differences are partly cultural, but factors related to when each society was
      formed, how it is organized, and how elections are structured undoubtedly play a
      role. Further analysis of these observations would be of interest from a
      sociological and a women's studies point of view.

PMID- 12512933
TI  - Myelin proteolipid protein-induced aggregation of lipid vesicles: efficacy of the
      various molecular species.
AB  - The different molecular species that form the myelin proteolipid protein family
      were isolated by size-exclusion and ion-exchange chromatography in organic
      solvents and their adhesive properties were tested using a vesicle aggregation
      assay. Addition of the major proteolipid (PLP) to phosphatidylcholine-cholesterol
      vesicles caused their clustering as determined by increase in O.D.(450 nm) and by
      transmission electron microscopy. A small fraction of the aggregated vesicles
      underwent fusion as determined by resonance energy transfer experiments. Vesicle
      aggregation by PLP, but not the dissociation of the aggregates, was influenced by
      pH suggesting that electrostatic interactions are important only during cluster
      formation. Cleavage of disulfide bonds and methylation of carboxyl groups in PLP
      greatly reduced the aggregating activity, indicating that the process is
      dependent on the protein's conformation. Unexpectedly, the proteolipid DM-20 was
      also effective at inducing the clustering of neutral lipid vesicles. In contrast,
      three protein fractions comprising the naturally-occurring PLP fragments 1
      107/112, 113/125-276 and 129/131-276, bearing different net charges, displayed a
      much lower activity. In addition, trypsin digestion of PLP resulted in a
      progressive decrease in the protein's ability to induce vesicle aggregation which
      coincided with the disappearance of the full-length molecule. Together, these
      results suggest that even large PLP fragments cannot fulfill the adhesive
      function of the intact protein.

PMID- 12512934
TI  - The structure and function of myelin: from inert membrane to perfusion pump.
AB  - The goal of this overview is to propose a novel structure/function model of
      central nervous system myelin. Although myelin is known to be a compact
      multilamellar structure that wraps around axons, the biologic role this structure
      plays in the nervous system remains an enigma. One means of ascertaining myelin's
      biologic role is by analyzing its structure. The recent discovery of tight
      junctions in myelin may be the key that unlocks the mysterious black box of
      myelin structure/function. Tight junctions in other cell types are invariably
      adjacent to adherens junctions, with both of these junctional plaques playing
      critical roles in paracellular barrier function, i.e., adhesion of cell
      membranes, signal transduction, and fluid movement between cells via aqueous
      pores and channels. The application of current knowledge about junctional plaques
      to myelin is an original concept. This knowledge, taken together with evidence
      from studies of normal and pathologic myelin, supports the possibility that a
      primary function of junctional plaques in myelin is to perfuse the periaxonal
      space.

PMID- 12512935
TI  - P0 and myelin basic protein-like immunoreactivities following ligation of the
      sciatic nerve in the rat.
AB  - In this work we analyzed variations in the expression of MBPs and P0 in ligated
      sciatic nerves of young and adult rats at 3, 7, and 14 days postligation (PL), by
      immunohistochemistry and SDS-PAGE of isolated myelin. A protein redistribution
      was seen in the distal stump of ligated nerves with the appearance of
      immunoreactive clusters. Using the KS400 image analyzer, immunostained area
      values were obtained from the different nerves dissected. In adult rats, there
      was an increase of the immunostained area for MBP from 3 to 7 days PL, coincident
      with a reorganization of the marker in clusters, followed by a marked decrease at
      14 days. P0 immunolabeling gave similar results without, however, a decrease of
      the immunostained area at the longer survival time tested. Young animals showed
      an acceleration in the process of protein redistribution and digestion within
      ligated nerves, which followed a similar pattern as that of adult animals.
      Analysis by electrophoresis showed a marked decrease in P0 and MBP at 7 days PL
      in young rats and 14 days PL in adult rats. The functional significance of
      protein clustering within myelin in injured nerves deserves further analysis.

PMID- 12512936
TI  - Myosin light chain kinase inhibitors induce retraction of mature oligodendrocyte
      processes.
AB  - Mature oligodendrocytes emit numerous myelinating processes. Force generating
      molecules are required for process outgrowth and spreading. We have analyzed the
      effect of the myosin II light chain kinase inhibitors ML-7 and ML-9 in cultured
      oligodendrocytes. Both drugs affect oligodendrocyte cell shape, provoking a
      retraction of high order processes. Our results suggest that the adhesion of the
      myelinating processes to the substrate depends on MLC phosphorylation, thus
      likely implicating myosin IIA.

PMID- 12512938
TI  - Myelin P0: new knowledge and new roles.
AB  - Protein zero (P0) is an integral transmembrane glycoprotein that serves as the
      major protein component of peripheral nerve myelin and is a member of the
      immunoglobulin (IgG) gene superfamily. As a cell adhesion molecule, P0 mediates
      homophilic adhesive interactions between Schwann cell plasma membranes and is a
      key structural constituent of both the major dense line and intraperiod line of
      compact myelin. Both the extracellular and cytoplasmic domains contribute to
      these interactions and evidence indicates that the post-translational
      modifications of the molecule, including glycosylation, acylation and
      phosphorylation, play an important modulatory role in adhesion and likely in the
      proper trafficking of P0 from the endoplasmic reticulum to the plasma membrane as
      well. Structural and genetic studies indicate that mutations in P0 producing
      human demyelinating diseases probably do so by perturbing or preventing
      homophilic interactions during myelination, or by producing cellular toxicity or
      an unstable myelin sheath. A variety of transcription factors, growth factors and
      neurosteroids both directly and indirectly influence P0 gene expression during
      maturation of the myelinating Schwann cell. Besides its structural function in
      myelin, P0 may have roles in the delivery of other Schwann cell proteins to their
      proper location, especially at or near nodes of Ranvier, and in neuronal-glial
      interactions.

PMID- 12512937
TI  - Myelin biogenesis: vesicle transport in oligodendrocytes.
AB  - Intracellular trafficking of membranes plays an essential role in the biogenesis
      and maintenance of myelin. The requisite proteins and lipids are transported from
      their sites of synthesis to myelin via vesicles. Vesicle transport is tightly
      coordinated with synthesis of lipids and proteins. To maintain the structural and
      functional organization of oligodendrocytes it is essential synchronize the
      various pathways of vesicle transport and to coordinate vesicle transport with
      reorganization of cytoskeleton. The systems that regulate the targeting of
      protein to myelin by vesicle transport are now being described. Here we review
      the current knowledge of these systems including those involved in (a) protein
      folding, (b) protein sorting and formation of carrier vesicles, (c) vesicle
      transport along elements of the cytoskeleton, and (d) vesicle targeting/fusion.

PMID- 12512939
TI  - Hyperglycemia triggers abnormal signaling and proliferative responses in Schwann
      cells.
AB  - Peripheral neuropathy is a serious diabetic complication. Delayed nerve
      regeneration in diabetic animal models suggests abnormalities in
      proliferation/differentiation of Schwann cells (SC). We recently reported that
      endothelins (ETs) regulate proliferation and phenotype in primary and
      immortalized SC (iSC). We now investigated changes in the effects of ETs on SC
      proliferation and signaling in nerve segments from streptozotocin-induced
      diabetic rats and in iSC exposed to high glucose. Cultured explants from diabetic
      rats displayed a delay in the time-course of [3H]-thymidine incorporation as well
      as enhanced sensitivity to endothelin-1 (ET-1) or insulin. iSC cultured in high
      (25 mM) glucose-containing media also exhibited higher [3H]-thymidine
      incorporation, along with an enhanced activation of p38 mitogen-activated protein
      kinase and phospholipase C in response to ET-1 or platelet-derived growth factor
      as compared to controls (5.5 mM glucose). These studies support an extra-vascular
      role of ETs in peripheral nerves and SC. The increased sensitivity to ET-1 in
      nerves and iSC exposed to high glucose may contribute to abnormal SC
      proliferation characterizing diabetic neuropathy.

PMID- 12512940
TI  - Overexpression of the 3'-untranslated region of myelin proteolipid protein mRNA
      leads to reduced expression of endogenous proteolipid mRNA.
AB  - The current studies focus on what mechanisms regulate the concentration of PLP
      mRNA in cells. The PLP mRNA is very stable and these studies suggest that its
      stability is regulated by a trans-acting factor specific to oligodendrocytes. In
      order to test whether the 3'untranslated region (3'UTR) of the PLP mRNA might
      regulate PLP RNA stability, C6 cells were transfected with cDNAs that expressed
      either luciferase or luciferase fused to the 3'UTR of PLP. Although transgene
      expression was low, in cells transfected with the PLP 3'UTR, there was a
      significant decrease in the endogenous PLP mRNA. These cells showed a distinct
      change in morphology and in adhesion properties. Thus, there may be a role for
      plp gene products in cell adhesion, which was downregulated in these cells, or an
      unknown function may be encoded by the PLP 3'UTR. Transgenic mice that
      overexpress enhanced green fluorescent protein fused to the PLP 3'UTR under
      control of PLP regulatory sequences were tested for the expression of the
      endogenous PLP mRNA. Three of four lines of transgenic mice had decreased
      endogenous PLP mRNA, relative to their non-transgenic littermates; the EGFP-PLP
      3'UTR mouse line that expressed the highest level of transgene mRNA had a 54%
      reduction in PLP mRNA. We hypothesize that the PLP mRNA is regulated by elements
      in the 3'UTR and stabilizing proteins specific to oligodendrocytes, and that in
      cells that overexpress the PLP 3'UTR, these stabilizing proteins may be
      insufficient to maintain the normal level of the endogenous PLP mRNA.

PMID- 12512941
TI  - Induction of oligodendrocyte fate during the formation of the vertebrate neural
      tube.
AB  - The development of the central nervous system (CNS) comprises a series of
      inductive and transforming events that includes rostro-caudal and dorso-ventral
      patterning, neuroglial specification and extensive cell migration. The patterning
      of the neural tube is also characterized by the transcription of specific genes,
      which encode for morphogens and transcription factors essential for cell fate
      specification. The generation of oligodendrocytes, the myelin forming glial cells
      in the CNS, appears to be restricted to specific domains localized in the ventral
      neuroepithelium. Signaling mediated by sonic hedgehog (Shh) seems to command the
      early phase of the specification of uncommitted neural stem cells into the
      oligodendroglial lineage. Once generated, oligodendrocyte progenitors have to
      follow a developmental program that involves changes in cell morphology,
      migratory capacity and sensitivity to extracellular trophic factors before
      becoming mature myelinating cells. This minireview aims to discuss molecular
      aspects of the early induction of oligodendroglial fate during the formation of
      the CNS.

PMID- 12512942
TI  - Pathways that control cortical F-actin dynamics during secretion.
AB  - Chromaffin cells possess a mesh of filamentous actin underneath the plasma
      membrane which acts as a barrier to the chromaffin vesicles access to exocytotic
      sites. Disassembly of cortical F-actin in response to stimulation allows the
      movement of vesicles from the reserve pool to the release-ready vesicle pool and,
      therefore, to exocytotic sites. The dynamics of cortical F-actin is controlled by
      two mechanisms: a) stimulation-induced Ca2+ entry and scinderin activation and b)
      protein kinase C (PKC) activation and MARCKS phosphorylation as demonstrated here
      by experiments with recombinant proteins, antisense olygodeoxynucleotides and
      vector mediated transient expressions. Under physiological conditions (i.e.,
      cholinergic receptor stimulation followed by Ca2+ entry), mechanism (a) is the
      most important for the control of cortical F-actin network whereas when Ca2+ is
      released from intracellular stores (i.e., histamine stimulation) cortical F-actin
      is regulated mainly by mechanism b.

PMID- 12512943
TI  - The degradation of amyloid beta as a therapeutic strategy in Alzheimer's disease
      and cerebrovascular amyloidoses.
AB  - The deposition of 4-kDa amyloid beta peptide in the brain is a prominent feature
      of several human diseases. Such process is heterogeneous in terms of causative
      factors, biochemical phenotype, localization and clinical manifestations. Amyloid
      beta accumulates in the neuropil or within the walls of cerebral vessels, and
      associates with dementia or stroke, both hereditary and sporadic. Amyloid beta is
      normally released by cells as soluble monomeric-dimeric species yet, under
      pathological conditions, it self-aggregates as soluble oligomers or insoluble
      fibrils that may be toxic to neurons and vascular cells. Lowering amyloid beta
      levels may be achieved by inhibiting its generation from the amyloid beta
      precursor protein or by promoting its clearance by transport or degradation. We
      will summarize recent findings on brain proteases capable of degrading amyloid
      beta with a special focus on those enzymes for which there is genetic, transgenic
      or biochemical evidence suggesting that they may participate in the proteolysis
      of amyloid beta in vivo. We will also put in perspective their possible
      utilization as therapeutic agents in amyloid beta diseases.

PMID- 12512944
TI  - Apoptosis in Schwann cell cultures is closely interrelated with the activity of
      the ubiquitin-proteasome proteolytic pathway.
AB  - Although the participation of the ubiquitin-dependent pathway and of the
      proteasome in apoptosis has been proposed, its role in this process is not yet
      clearly defined. In previous studies, we have shown that in the central nervous
      system of the rat, programmed cell death and the ubiquitin-dependent proteolytic
      pathway are closely related to each other and that different types of neurons and
      of glial cells, shown different types of correlation between the two phenomena.
      In this work, we have used lactacystin, a highly specific inhibitor of the
      proteasome, to explore in Schwann cell cultures the relationship between the
      activity of the Ub-dependent pathway and apoptosis. Apoptosis was explored
      analyzing changes in nuclear morphology, using the Annexin V assay and by flow
      cytometry. Activity of caspase-3 was also measured. Changes in the levels of
      ubiquitin-protein conjugates and of the ubiquitin activating enzymes, E1, as well
      as expression of proteins that instruct the cells to apoptosis (p53, NFkappaB
      IkappaB, Bcl2), or that participate in the control and regulation of the cell
      cycle, were also examined. Our results indicate that the decrease in the activity
      of the proteasome induced by lactacystin in Schwann cells, induces apoptotic cell
      death through changes in the concentration of certain key proteins that are
      involved in the apoptosis-signaling pathways.

PMID- 12512945
TI  - GD3 expression in CHO-K1 cells increases growth rate, induces morphological
      changes, and affects cell-substrate interactions.
AB  - We have generated a panel of CHO-K1 cell clones with different glycolipid
      compositions by stable transfection of appropriate glycosyltransferases and
      studied the morphological and growth phenotype of a clone stably expressing Sial
      T2. Compared with the GM3 expressing parental cells, Sial-T2 transfectants show
      low expression of GM3 and neo expression of GD3 and GT3. These cells show about
      60% reduction of the mean cell area, and about 2-fold increase of the mean colony
      area and growth rate. Cells over expressing Sial-T2 showed a flattened
      appearance, and with time in culture they detached from the substrate leaving
      adhered material that was GD3 immunoreactive. No apoptotic or proteome
      differences could be detected in the Sial-T2 transfectants. Thus, increased
      expression of GD3 and GT3 influence parameters of growth and social behavior of
      CHO-K1 cells. However, the molecular and cellular basis underlying these
      influences requires further investigation.

PMID- 12512946
TI  - Demonstration of pyruvate recycling in primary cultures of neocortical astrocytes
      but not in neurons.
AB  - Pyruvate recycling was studied in primary cultures of mouse cerebrocortical
      astrocytes, GABAergic cerebrocortical interneurons, and co-cultures consisting of
      both cell types by measuring production of [4-(13)C]glutamate from [3
      (13)C]glutamate by aid of nuclear magnetic resonance spectroscopy. This change in
      the position of the label can only occur by entry of [3-(13)C]glutamate into the
      tricarboxylic acid (TCA) cycle, conversion of labeled alpha-ketoglutarate to
      malate or oxaloacetate, malic enzyme-mediated decarboxylation of malate to
      pyruvate or phosphoenolpyruvate carboxykinase-mediated conversion of oxaloacetate
      to phosphoenolpyruvate and subsequent hydrolysis of the latter to pyruvate, and
      introduction of the labeled pyruvate into the TCA cycle, i.e., after exit of the
      carbon skeleton of pyruvate from the TCA cycle followed by re-entry of the same
      pyruvate molecules via acetyl CoA. In agreement with earlier observations,
      pyruvate recycling was demonstrated in astrocytes, indicating the ability of
      these cells to undertake complete oxidative degradation of glutamate. The
      recycled [4-(13)C]glutamate was not further converted to glutamine, showing
      compartmentation of astrocytic metabolism. Thus, absence of recycling into
      glutamine in the brain in vivo cannot be taken as indication that pyruvate
      recycling is absent in astrocytes. No recycling could be demonstrated in the
      cerebrocortical neurons. This is consistent with a previously demonstrated lack
      of incorporation of label from glutamate into lactate, and it also indicates that
      mitochondrial malic enzyme is not operational. Nor was there any indication of
      pyruvate recycling in the co-cultures. Although this may partly be due to more
      rapid depletion of glutamate in the co-cultures, this observation at the very
      least indicates that pyruvate recycling is not up-regulated in the neuronal
      astrocytic co-cultures.

PMID- 12512947
TI  - Induction of apoptosis in cerebellar granule cells by 2,4-dichlorophenoxyacetic
      acid.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) and derivatives are herbicides widely used
      in Argentina and other parts of the world. Exposure to 2,4-D, its ester and salt
      formulations, have been associated with a range of adverse health effects in
      humans and different animal species, from embryotoxicity and teratogenicity to
      neurotoxicity. In this work, we demonstrate that after 24 hs of treatment with 1
      and 2 mM 2,4-D there is an induction of apoptosis in cerebellar granule cells
      (CGC) in culture. However, with 2 mM 2,4-D one population of CGC developed
      features of apoptosis while another appeared to die by necrosis. This process is
      associated with an increase in caspase-3 activity after 12 hs of treatment with
      the herbicide, which is preceded by cytochrome c release from the mitochondria.
      Treatment of CGC with 2,4-D appears to induce apoptosis by a direct effect on
      mitochondria producing cytochrome c release and consequently activation of
      caspase-3, being mitochondrial damage sufficient for triggering the events that
      may cause apoptosis.

PMID- 12512948
TI  - Higher order chromatin degradation: implications for neurodegeneration.
AB  - Higher order chromatin degradation (HOCD) is a hallmark of programmed cell death.
      HOCD is mediated by enzymatic digestion of the DNA backbone at matrix attachment
      regions, and ultimately results in the excision of chromatin loops and their
      oligomers from chromosomes. We have recently demonstrated that hydrogen peroxide
      (H2O2), the major mediator of oxidative stress, rapidly induces HOCD. This
      demonstration allowed us to characterize several kinetic features of HOCD.
      Moreover, H2O2-induced HOCD provides a mechanistic link between oxidative stress
      and the pathology of neurodegeneration. Thus, in acute neurodegenerative
      conditions, which feature severe oxidative stress, H2O2-induced HOCD efficiently
      dismantles the genome, and thus, irreversibly commits cells to death. In chronic
      neurodegenerative conditions, which feature sublethal but perennial oxidative
      stress, cells undergo only a partial fragmentation of the genome via H2O2-induced
      HOCD. If unrepaired of improperly repaired, such a partial fragmentation leads to
      the generation and accumulation of somatic mutations that are likely to play the
      key role in delayed degeneration and death of neural cells.

PMID- 12512949
TI  - Cloning of rat olfactory bulb tubulin tyrosine ligase cDNA: a dominant negative
      mutant and an antisense cDNA increase the proliferation rate of cells in culture.
AB  - In this paper we describe the cloning of rat olfactory bulb tubulin tyrosine
      ligase (TTL) cDNA, and investigate the physiological role of TTL in cultured CHO
      K1 cells. Comparison of the deduced amino acid sequence of rat TTL cDNA with
      those of bovine and pig showed approximately 90% of identity. Transient
      transfection of CHO-K1 cells with a dominant negative mutant of TTL that contains
      the binding site to the substrate (tubulin) but not the catalytic domain,
      significantly decreased the endogenous TTL activity as determined in vitro.
      Similar results were obtained using a construction encoding for the antisense
      sequence of TTL. The reduction in TTL activity is not accompanied by a decrease
      in the tyrosination levels of microtubules, as judged by immunofluorescence
      analysis. Strikingly, the number of cells in the plates transfected with the
      mutant TTL or the antisense TTL cDNA was, after 72 h of culture, two and three
      times higher, respectively, than the number of cells in the control plates. These
      results support the hypothesis that TTL may play a role in the regulation of the
      cell cycle in living cells.

PMID- 12512950
TI  - Alternative splicing in the brain of mice and rats generates transferrin
      transcripts lacking, as in humans, the signal peptide sequence.
AB  - Transferrin (Tf), the iron-transport protein of vertebrate serum, is mainly
      synthesized in hepatocytes but is also found in other cell-types including
      oligodendrocytes. Our laboratory has characterized in a human oligodendrial cell
      line the presence of a new Tf transcript containing an alternative exon 1b
      replacing the classical exon 1 and conducting to the elimination of the signal
      peptide sequence. In this manuscript, we show by RT-PCR and 5'-RACE experiments
      that alternative transcripts also exist in mouse and rat and are found in brain
      mRNA preparations. Mouse alternative first exon is homologous to human exon 1b
      while rat Tf gene was found to use a new first exon named 1c. In all species, the
      alternative transcript does not contain the signal peptide sequence and possibly
      encode for a Tf protein devoid of signal peptide showing that this phenomenon is
      not restricted to human gene. We also present genomic sequence data from the
      previously unknown 5' genomic rat region, which allowed the alignment of the
      alternative exons 1 in the three species.

PMID- 12512951
TI  - Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP
      induction in the medial vestibular nuclei.
AB  - LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing
      phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final
      reactions for the synthesis of PAF. Their activities, assayed in the homogenate
      of rat brain stem slices and under their optimal conditions, increased 5 min
      after high frequency stimulation of vestibular afferents, inducing LTP in the
      medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing
      phosphocholinetransferase, was not affected. Sixty minutes from the induction of
      LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher
      with respect to 5 min test stimulated control. We used AP-5 to verify whether
      this increase was strictly dependent upon LTP induction, which requires NMDA
      receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF
      synthesizing phosphocholinetransferase activities increased, but they were
      reduced after high frequency stimulation under AP-5. In conclusion, we have
      demonstrated that the activities of PAF-synthesizing enzymes are activated soon
      after the induction of LTP and that this effect is linked to the activation of
      NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP,
      might be due to glutamate enhancement but, in neurons showing LTP and under
      normal conditions, the activation of potentiation mechanisms is critical for the
      enhancement of enzyme activities.

PMID- 12512953
TI  - Molecular mechanisms of memory retrieval.
AB  - Memory retrieval is a fundamental component or stage of memory processing. In
      fact, retrieval is the only possible measure of memory. The ability to recall
      past events is a major determinant of survival strategies in all species and is
      of paramount importance in determining our uniqueness as individuals. Most
      biological studies of memory using brain lesion and/or gene manipulation
      techniques cannot distinguish between effects on the molecular mechanisms of the
      encoding or consolidation of memories and those responsible for their retrieval
      from storage. Here we examine recent findings indicating the major molecular
      steps involved in memory retrieval in selected brain regions of the mammalian
      brain. Together the findings strongly suggest that memory formation and retrieval
      may share some molecular mechanisms in the hippocampus and that retrieval
      initiates extinction requiring activation of several signaling cascades and
      protein synthesis.

PMID- 12512952
TI  - Circadian phototransduction and the regulation of biological rhythms.
AB  - The vertebrate circadian system that controls most biological rhythms is composed
      of multiple oscillators with varied hierarchies and complex levels of
      organization and interaction. The retina plays a key role in the regulation of
      daily rhythms and light is the main synchronizer of the circadian system. To
      date, the identity of photoreceptors/photopigments responsible for the
      entrainment of biological rhythms is still uncertain; however, it is known that
      phototransduction must occur in the eye because light entrainment is lost with
      eye removal. The retina is also rhythmic in physiological and metabolic
      activities as well as in gene expression. Retinal oscillators may act like clocks
      to induce changes in the visual system according to the phase of the day by
      predicting environmental changes. These oscillatory and photoreceptive capacities
      are likely to converge all together on selected retinal cells. The aim of this
      overview is to present the current knowledge of retinal physiology in relation to
      the circadian timing system.

PMID- 12512954
TI  - The oxidant defense system in human neuroblastoma IMR-32 cells predifferentiation
      and postdifferentiation to neuronal phenotypes.
AB  - Differentiated neurons were investigated for their susceptibility to oxidative
      damage based on variations in the oxidant defense system occurring during
      differentiation. The main antioxidant enzymes and substances in human
      neuroblastoma (IMR-32) cells were evaluated pre- and postdifferentiation to a
      neuronal phenotype. The activity of CuZn superoxide dismutase (CuZnSOD) and Mn
      superoxide dismutase (MnSOD) and the concentration of CuZnSOD were higher, but
      the activity and concentration of catalase were lower after differentiation.
      Differentiated cells had higher activity of glutathione peroxidase (GPx), lower
      concentration of total glutathione, a higher ratio of oxidised/reduced
      glutathione and lower activity of glucose-6-phosphate dehydrogenase than
      undifferentiated cells. We conclude that differentiated neuronal cells may be
      highly susceptible to oxidant-mediated damage based on the relative activities of
      the main antioxidant enzymes and on a limited capacity to synthesise and/or
      recycle glutathione.

PMID- 12512955
TI  - Differential effects of three inhibitors of glycosphingolipid biosynthesis on
      neuronal differentiation of embryonal carcinoma stem cells.
AB  - Gangliosides have been implicated in having important roles in neural
      development. It has been shown that disruption of ganglioside biosynthesis
      inhibits neurite outgrowth. However, many contradictory results have been
      reported. The inconsistency of these reports may result from the differential use
      of neuronal cell lines and inhibitors for ganglioside biosynthesis. In order to
      clarify the inconsistency in these studies, we utilized an in vitro neuronal
      differentiation model using an embryonic caricinoma (EC) stem cell line to
      elucidate the relationship between ganglioside expression and neural development.
      These cells were exposed to three different inhibitors of glucosylceramide
      synthase, the first enzyme committed for the biosynthesis of most of the brain
      gangliosides. All three inhibitors, D-threo-1-phenyl-2-decanoylamino-3-morphlino
      1-propanol (D-PDMP), D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol
      (D-PPPP), and N-butydeoxynojirimycin (NB-DNJ) can inhibit greater than 90% of
      ganglioside biosynthesis at certain concentrations, respectively. D-PDMP
      significantly slowed down cellular proliferation in undifferentiated P19 EC
      cells, inhibited neurite outgrowth, and eventually caused cell death in
      differentiated cells. However, no retardation in cell growth, neuronal
      differentiation, and neurite outgrowth was observed in cultures treated with D
      PPPP or NB-DNJ despite the depletion of gangliosides. These results indicate that
      the effect of D-PDMP on cellular proliferation, neurite outgrowth, and survival
      of differentiated cells is independent of the inhibition of ganglioside
      biosynthesis.

PMID- 12512956
TI  - Age-associated changes in central nervous system glycerolipid composition and
      metabolism.
AB  - In this review, changes in brain lipid composition and metabolism due to aging
      are outlined. The most striking changes in cerebral cortex and cerebellum lipid
      composition involve an increase in acidic phospholipid synthesis. The most
      important changes with respect to fatty acyl composition involve a decreased
      content in polyunsaturated fatty acids (20:4n-6, 22:4n-6, 22:6n-3) and an
      increased content in monounsaturated fatty acids (18:1n-9 and 20:1n-9), mainly in
      ethanolamine and serineglycerophospholipids. Changes in the activity of the
      enzymes modifying the phospholipid headgroup occur during aging. Serine
      incorporation into phosphatidylserine through base-exchange reactions and
      phosphatidylcholine synthesis through phosphatidylethanolamine methylation
      increases in the aged brain. Phosphatidate phosphohydrolase and phospholipase D
      activities are also altered in the aged brain thus producing changes in the lipid
      second messengers diacylglycerol and phosphatidic acid.

PMID- 12512957
TI  - Long-term effects of prenatal stress on dopamine and glutamate receptors in adult
      rat brain.
AB  - Prenatal stress greatly influences the ability of an individual to manage
      stressful events in adulthood. Such vulnerability may result from abnormalities
      in the development and integration of forebrain dopaminergic and glutamatergic
      projections during the prenatal period. In this study, we assessed the effects of
      prenatal stress on the expression of selective dopamine and glutamate receptor
      subtypes in the adult offsprings of rats subjected to repeated restraint stress
      during the last week of pregnancy. Dopamine D2-like receptors increased in dorsal
      frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA1 region and
      core region of nucleus accumbens (NAc) of prenatally stressed rats compared to
      control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal
      CA1, medial caudate-putamen, as well as in shell and core regions of NAc. Group
      III metabotropic glutamate receptors increased in MPC and DFC of prenatally
      stressed rats, but remained unchanged in all other regions examined. These
      results indicate that stress suffered during the gestational period has long
      lasting effects that extend into the adulthood of prenatally stressed offsprings.
      Changes in dopamine and glutamate receptor subtype levels in different forebrain
      regions of adult rats suggest that the development and formation of the
      corticostriatal and corticolimbic pathways may be permanently altered as a result
      of stress suffered prenatally. Maldevelopment of these pathways may provide a
      neurobiological substrate for the development of schizophrenia and other
      idiopathic psychotic disorders.

PMID- 12512958
TI  - Expression of the p75 TNF receptor is linked to TNF-induced NFkappaB
      translocation and oxyradical neutralization in glial cells.
AB  - Tumor necrosis factor (TNF)-family cytokines induce reactive oxygen species (ROS)
      that injure vulnerable populations of brain cells. Among glia, oligodendrocytes
      are particularly susceptible to TNF-induced ROS whereas microglia are protected.
      We previously found that oligodendrocytes in vitro predominantly express the p55
      type-1 TNF receptor, while microglial cells express both type-1 and p75 type-2
      receptors. We hypothesized that differential TNF receptor expression and
      attendant signaling underlies the relative vulnerability of oligodendrocytes,
      versus microglia, to TNF-induced injury. To test this hypothesis, purified
      cultures of glial cells were incubated 0-48 hr with TNFalpha or lymphotoxin
      alpha, following which levels of ROS, glutathione (GSH), nuclear factor kappa-B
      (NFkappaB) translocation, and anti-oxidant proteins and activity were measured.
      48 hr exposure to TNF increased ROS levels 28% and decreased GSH levels 17% in
      oligodendrocytes, but decreased levels ROS levels 24% and increased GSH levels
      112% increase in microglia. Thirty to 180 min exposure to TNF increased NFkappaB
      nuclear translocation to a greater extent and for a longer time in microglia
      versus oligodendrocytes, and this was followed 24-48 hr later with 3- to 13-fold
      increases in microglia manganese superoxide dismutase protein levels and 6-fold
      increases in enzyme activity. Collectively, these data suggest that signals
      transduced through the p75 receptor activate anti-oxidant mechanisms that protect
      microglia from TNF-induced injury. Lacking such signals, oligodendrocytes are
      considerably more vulnerable to the injurious effects of TNF.

PMID- 12512959
TI  - Effects of muscarinic toxins MT1 and MT2 from green mamba on different muscarinic
      cholinoceptors.
AB  - MT1 and MT2, polypeptides from green mamba venom, known to bind to muscarinic
      cholinoceptors, behave like muscarinic agonists in an inhibitory avoidance task
      in rats. We have further characterised their functional effects using different
      preparations. MT1 and MT2 behaved like relatively selective muscarinic M1
      receptor agonists in rabbit vas deferens, but their effects were not reversed by
      washing or prevented by muscarinic antagonists, although allosteric modulators
      altered responses to MT1. Radioligand binding experiments indicated that both
      toxins irreversibly inhibited [3H]N-methylscopolamine binding to cloned
      muscarinic M1 and M4 receptors, and reduced binding to M5 subtype with lower
      affinity, while they reversibly inhibited the binding of [3H]prazosin to rat
      cerebral cortex and vas deferens, with 20 fold lower affinity. High
      concentrations of MT1 reversibly blocked responses of vas deferens to
      noradrenaline. MT1 and MT2 appear to irreversibly activate muscarinic M1
      receptors at a site distinct from the classical one, and to have affinity for
      some alpha-adrenoceptors.

PMID- 12512960
TI  - Neurotensin effect on Na+, K+-ATPase is CNS area- and membrane-dependent and
      involves high affinity NT1 receptor.
AB  - We have previously shown that peptide neurotensin inhibits cerebral cortex
      synaptosomal membrane Na+, K+-ATPase, an effect fully prevented by blockade of
      neurotensin NT1 receptor by antagonist SR 48692. The work was extended to analyze
      neurotensin effect on Na+, K+-ATPase activity present in other synaptosomal
      membranes and in CNS myelin and mitochondrial fractions. Results indicated that,
      besides inhibiting cerebral cortex synaptosomal membrane Na+, K+-ATPase,
      neurotensin likewise decreased enzyme activity in homologous striatal membranes
      as well as in a commercial preparation obtained from porcine cerebral cortex.
      However, the peptide failed to alter either Na+, K+-ATPase activity in cerebellar
      synaptosomal and myelin membranes or ATPase activity in mitochondrial
      preparations. Whenever an effect was recorded with the peptide, it was blocked by
      antagonist SR 48692, indicating the involvement of the high affinity neurotensin
      receptor (NT1), as well as supporting the contention that, through inhibition of
      ion transport at synaptic membrane level, neurotensin plays a regulatory role in
      neurotransmission.

PMID- 12512961
TI  - Search for alpha4 and alpha7 nicotinic acetylcholine receptor markers in a
      pedigree of benign familial infantile convulsions (BFIC).
AB  - In this study we investigate the possible involvement of the recently reported
      locus for benign familial infantile convulsions (BFIC) in human chromosome 19 and
      that of the neuronal acetylcholine receptor alpha4 (CHRNA4) and alpha7 (CHRNA7)
      subunits in a family with at least twelve clinically diagnosed cases of BFIC. Six
      polymorphic microsatellite markers covering the BFIC locus on chromosomal region
      19q, one marker for CHRNA4 (chromosome 20) and two for CHRNA7 (chromosome 15)
      were used for the screening. The two-point lod score analysis showed no evidence
      of BFIC phenotype on chromosome 19. Similarly, when markers for chromosome 20
      (CHRNA4 intron1, Amplimer: CHRNA4. PCR.1) and chromosome 15 (D15S165 and
      D15S1010) were used, score analysis showed no indication of linkage. The most
      likely interpretation of these results is that BFIC is a genetically
      heterogeneous form of epilepsy.

PMID- 12512962
TI  - Late radiation morbidity in a patient with carcinoma of the cervix.
AB  - The Grand Round was held at the Christie Hospital on the 26 November 2001. It
      followed a talk by Professor Kate Vallis of the Princess Margaret Hospital in
      Toronto on, "A functional genomics approach to understanding normal issue
      response and ionizing radiation".

PMID- 12512963
TI  - The effect of smoking on tumour oxygenation and treatment outcome in cervical
      cancer.
AB  - AIM: Tumour hypoxia is associated with an increased risk of cervical tumour
      recurrence and death. Because smoking is a modifiable behaviour, it is important
      to establish the importance of smoking as a prognostic factor. We hypothesized
      that there is an association between smoking and tumour hypoxia, and that smoking
      adversely affects radiation response and survival. METHODS: A smoking history was
      obtained from 100 of 115 patients with cervical cancer entered into a prospective
      study of tumour oxygenation. Eighty-seven of these had clinically evident disease
      and radiation therapy alone was the planned treatment. Patients who smoked within
      2 weeks of commencing radiation therapy were considered smokers, and the amount
      that they smoked was recorded in packs per day. Patients who had never smoked or
      quit at least 2 weeks prior to radiation therapy were considered non-smokers.
      Tumour oxygenation was determined using the Eppendorf polarographic oxygen
      electrode and tumour oxygenation is represented by the hypoxic proportion HP5 (%
      of pO2 measurements <5 mmHg). RESULTS: There was no significant association
      between smoking and tumour hypoxia (P=0.3), haemoglobin (P=0.6) nor tumour size
      (P=0.1). Progression-free survival at 3 years was 56% for non-smokers and 44% for
      smokers (P=0.23). In both univariate and multivariate analysis, neither smoking
      status nor amount smoked were significant predictors of progression-free survival
      or local control. CONCLUSIONS: There was no significant association between
      smoking and tumour hypoxia, treatment response or survival in this study of
      patients with cervix cancer.

PMID- 12512964
TI  - Carcinoma cervix with metastasis to deltoid muscle.
AB  - Skeletal muscles are rare metastatic sites despite their rich blood supply and
      the fact that the muscular mass of the body accounts for a large percentage of
      the total body weight. They account for less than 1% of all malignant metastases
      of haematogenous origin. Menard and Parache, Ann Med Interne Paris 1991;142:423
      428. Skeletal muscle metastasis in cervical cancer have been infrequently
      reported. In this case report, we detail a case of cervical cancer who developed
      a painful swelling of the right shoulder which on investigation, was found to be
      skeletal muscle metastases.

PMID- 12512965
TI  - High-dose epirubicin and cisplatin in locally advanced undifferentiated
      nasopharyngeal carcinoma.
AB  - AIM: Undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive tumour;
      a randomized study evaluating neoadjuvant chemotherapy with
      bleomycin/epidoxorubicin/cisplatin (BEC) in addition to conventional radiotherapy
      has resulted in a better disease-free survival in the chemotherapy arm. The
      bleomycin infusion in the BEC regimen has necessitated hospitalization for the
      infusion, and resulted in serious pulmonary toxicity. This study has aimed to
      omit the bleomycin, and test the efficacy and toxicity of cisplatin (C) and a
      higher dose of epidoxorubicin (EPI) in patients with locally advanced UNPC.
      METHODS: Seventy-one patients with locally advanced UNPC were treated with three
      cycles of C 100 mg/m2 day 1, and EPI 100 mg/m2 day 1 every 3 weeks followed by
      conventional radiotherapy of 70 Gy. RESULTS: Neoadjuvant chemotherapy was well
      tolerated. There was only 1-week delay in 14.3% of the patients and no dose
      modification. Grade III-IV neutropenia occurred in 18.9% of the cycles: none of
      the patients developed neutropenic fever. No patient progressed during
      chemotherapy, the complete response rate was 26.8% (95% CI = 16.9-38.6) and the
      partial response rate was 59.1% (95% CI = 46.8-70.7) for an objective response
      rate of 85.9% (95% CI = 75.6-93.0) at the end of the three cycles of
      chemotherapy. After the completion of radiotherapy, the complete response rate
      increased to 81.7% (95% CI = 70.7-89.9) and the objective response increased to
      91.5% (95% CI = 82.5-96.8). The median disease-free interval and the median
      survival have not been reached. The 5-year disease-free and overall survival
      rates are 53.0% (95% CI = 43.7-62.0) and 57.2% (95% CI = 48.3-65.2),
      respectively. CONCLUSION: Neoadjuvant C and EPI, easily administered in the
      outpatient setting, is an effective and well-tolerated regimen in the treatment
      of locally advanced UNPC.

PMID- 12512966
TI  - Effect of deprivation on survival of patients with head and neck cancer: a study
      of 20,131 cases.
AB  - There is increasing evidence that, for many cancers, the survival of
      socioeconomically deprived patients is worse compared with those who are more
      affluent. This study provides additional evidence that this is true for patients
      with head and neck cancers. However, the detrimental effects of deprivation were
      not found to be lifelong, and in this study, were confined to the first 12-18
      months after diagnosis. After this there were no significant deprivation
      associated effects on subsequent survival. The reasons for the initial increased
      mortality in the deprived are not clear but may be related to more advanced
      stage, more biologically aggressive cancers, greater co-morbidity or worse
      treatment.

PMID- 12512967
TI  - Treatment of conjunctival lymphomas by beta-ray brachytherapy using a strontium
      90-yttrium-90 applicator.
AB  - We reviewed the outcome of the 10 patients (13 eyes) with localized, biopsy
      proven, low-grade lymphoma of the conjunctiva treated at our Department between
      1988 and 1997. All patients were treated by beta-ray brachytherapy using a
      bidirectional 90Sr-90Y ophthalmic applicator (Applicator SIA 2, Amersham plc).
      Total doses, prescribed at the surface of the applicator, varied between 40 Gy
      and 80 Gy. With a median follow-up of 78 months (range: 14 to 146 months), seven
      patients remained with no evidence of relapse (67.5% 10 year disease free
      survival). Local control was achieved in 10 out of 13 eyes (76.9%). Two of the
      three local relapses were marginal. One of these three patients also developed a
      metachronous lymphoma in the contralateral conjunctiva. These three patients
      underwent a second course of brachytherapy with 90Sr/90Y and remained free of
      second relapse 109, 68 and 33 months after salvage therapy. No cases of systemic
      relapse were observed. Late (LENT-SOMA) complications were of grade 2 in five
      eyes, of grade 3 in one eye and of grade 4 in one eye. Late complications of
      grade 2 or higher were observed in one out of five patients (20%) treated with
      doses lower or equal to 50 Gy and in six out of eight patients (75%) treated with
      doses higher than 50 Gy (P=0.086). Our data indicates that beta-ray brachytherapy
      was ultimately able to control most conjunctival lymphomas but carried a risk of
      late complications and marginal relapses that was possibly higher than the rates
      reported for other radiotherapy techniques.

PMID- 12512968
TI  - Gastric irradiation for low-grade MALT lymphoma of the stomach: report of two
      cases and review of the literature.
AB  - We report the case history of two patients treated with primary gastric
      irradiation for localized low-grade mucosa-associated lymphoid tissue (MALT)
      lymphoma of the stomach that failed to respond to anti-Helicobacter pylori
      antibiotics. One patient refused gastrectomy and the other was considered unfit
      for surgery. Both patients obtained a biopsy-confirmed complete response and are
      well and disease free after a median follow-up time of 28 months. A review of the
      literature on the treatment options for this condition has been undertaken.
      Gastric irradiation is an effective and safe alternative to gastrectomy in the
      treatment of low-grade MALT lymphoma of the stomach with the added advantage of
      organ preservation.

PMID- 12512969
TI  - Cervical neuropathy following mantle radiotherapy.
AB  - The majority of newly diagnosed patients with Hodgkin's lymphoma are expected to
      survive because of effective therapies established during the last 40 years. Long
      term observations from large populations of treated patients have disclosed a
      variety of late effects of the disease and its therapy that have contributed
      morbidity and excess mortality to Hodgkin's lymphoma survivors. As such
      complications have been recognized treatment approaches have been modified. Here
      we report a case of cervical neuropathy secondary to mantle radiotherapy, a
      complication not previously reported in the literature.

PMID- 12512970
TI  - Don't wait for a sensory level--listen to the symptoms: a prospective audit of
      the delays in diagnosis of malignant cord compression.
AB  - AIM: To report details concerning symptoms (especially pain) preceding the
      development of malignant cord compression (MCC); delays between onset/reporting
      of symptoms and confirmed diagnosis of MCC; accuracy of investigations carried
      out. METHODS: A prospective observational study examined the diagnosis,
      management and outcome of 319 patients diagnosed with MCC at three Scottish
      cancer centres between January 1998-April 1999. The process was considered from
      the perspectives of the patient, the GP and the hospital doctor. RESULTS: At
      diagnosis, most patients (82%) were either unable to walk or only able to do so
      with help. Pain was reported by nearly all patients interviewed (94%) and had
      been present for approximately 3 months (median=90 days). It was severe in 84% of
      cases, with the distribution and characteristics of nerve root pain in 79%. The
      site of pain did not correspond to the site of compression. Where reported,
      weakness and/or sensory problems had been noticed by the patient for some time
      before diagnosis (median intervals 20 and 12 days, respectively). Most patients
      reported early symptoms to their General Practitioner (GP) and diagnosis was
      established, following referral and investigation, approximately 2 months
      (median=66 days) later. CONCLUSION: Patients who develop spinal metastases are at
      risk of irreversible spinal cord damage. Weakness and sensory abnormalities are
      reported late and identified even later, despite patients having reported pain
      for a considerable time. Patients with cancer who describe severe back or spinal
      nerve root pain need urgent assessment on the basis of their symptoms, as signs
      may occur too late. Plain films and bone scans requested for patients in this
      audit predicted accurately the level of compression in only 21% and 19% of cases,
      respectively. The only accurate investigation to establish the presence and site
      of a compressive lesion is magnetic resonance imaging (MRI). A referral guideline
      based on suspicious symptoms in addition to suspicious signs is suggested.

PMID- 12512971
TI  - Management of spinal cord and cauda equina compression secondary to epidural
      metastatic disease in adults with malignant germ cell tumours.
AB  - AIM: To review the management and clinical outcome of 10 patients, presenting to
      a single centre with symptoms and signs of spinal cord or cauda equina
      compression secondary to epidural metastatic disease from a testicular germ cell
      cancer. METHODS: Clinical data regarding presenting history, physical
      examination, staging investigations, treatment and clinical outcome were
      retrospectively obtained from patient records. RESULTS: Eight patients exhibited
      neurological deficits at the time of initial presentation of germ cell cancer or
      as a first manifestation of relapse following dog leg irradiation. Four of these
      cases were managed with chemotherapy alone, with excellent neurological recovery,
      whilst four underwent decompressive laminectomy--in three cases prior to referral
      and in one case after commencing chemotherapy. Five of the eight patients
      relapsed. Four required further chemotherapy (high dose in two cases). The
      remaining patient underwent thoracic surgery, with resection of teratoma
      differentiated. Six of the eight patients are currently alive and disease free.
      Two patients had chemorefractory disease and died, though one was treated in the
      pre-cisplatin era. Two patients presented with cord compression as a feature of
      disease relapse following chemotherapy, and were managed with radiotherapy alone
      in an attempt to achieve local disease control and limit neurological
      dysfunction. However, both subsequently died with progressive disease.
      CONCLUSION: Epidural spinal cord or cauda equina compression is a rare
      complication of metastatic germ cell cancer, which can be successfully managed in
      chemo-naive patients with good neurological outcome.

PMID- 12512972
TI  - Chlorambucil and acute intermittent porphyria.
AB  - A 54-year-old women with quiescent acute intermittent porphyria (AIP) developed
      low-grade non-Hodgkin's lymphoma. She was successfully treated with chlorambucil
      without any significant rise in urinary proto-porphyrins. The case is described
      and a review of chemotherapy use in AIP is presented.

PMID- 12512973
TI  - Coeliac disease following high-dose chemotherapy.
AB  - This report describes an interesting case of severe diarrhoea following high-dose
      chemotherapy for non-Hodgkin's lymphoma. This caused significant morbidity and
      resolved on a gluten-free diet.

PMID- 12512974
TI  - Pasteurella multocida infection in a post-chemotherapy neutropenic host following
      cat exposure.
AB  - We report a case of Pasteurella multocida infection in a neutropenic patient.
      History of contact with animals is important, particularly in patients who
      present with localized cellulitis and neutropenic fever. Clinical features and
      treatment of the disease are discussed.

PMID- 12512975
TI  - Spinal cord compression as a complication of metastic epithelial ovarian cancer.

PMID- 12512976
TI  - Surgery or radiotherapy for bladder cancer?

PMID- 12512977
TI  - Choice of chemotherapy regimen for advanced colorectal cancer.

PMID- 12512978
TI  - Optimal therapy of primary ocular lymphoma.

PMID- 12512979
TI  - An introduction to quality of life assessment in oncology: the value of measuring
      patient-reported outcomes.
AB  - This article provides an introduction to the concepts of quality of life (QOL)
      research, including the documented uses and benefits of patient-reported
      outcomes. Health-related QOL data have been useful in clinical care studies,
      clinical trials, and cost-effectiveness studies. In the area of cancer treatment,
      such health-related QOL data have been influential on treatment decisions and
      cancer care. In addition, this article addresses the challenges resulting from
      more frequent use of patient-reported outcomes by researchers and physicians. In
      particular, the impact of the response-shift phenomenon is examined, as well as
      the time pressure, clinical constraints, and suboptimal communication skills that
      may hinder the transfer of information from patient to physician and/or
      researcher.

PMID- 12512980
TI  - Quality of life and symptom measures in oncology: an overview.
AB  - Improving quality of life (QOL) in oncology patients is an important therapeutic
      goal, and most treatment decisions are heavily influenced by their effect on QOL.
      Although measuring QOL has been a significant challenge because of a lack of
      consensus on the definition of QOL, research in this field has advanced rapidly.
      Numerous instruments now exist for measuring QOL and symptom burden, ranging from
      general health status measures to considerably more focused symptom measures. QOL
      measures have been routinely incorporated in clinical trials, and their use in
      clinical settings is strongly encouraged because their value in cancer patient
      management is now established. These measures also have a potential impact in the
      managed care environment because they provide information on patient satisfaction
      and quality of care provided. This article clarifies the definition of QOL,
      provides a brief overview of several useful measurement instruments, and
      addresses some common concerns encountered in measuring QOL in cancer patients.
      In addition, potential uses of such measures are explored and their value in
      various settings, including managed care, is highlighted.

PMID- 12512981
TI  - Quality of life measurements: a soft outcome--or is it?
AB  - In oncology research, quality of life (QOL) has been identified as the second
      most important outcome, with survival being the most important. The integration
      of QOL assessments into clinical practice and research presents some unique
      challenges. QOL outcomes are sometimes perceived to be soft, as opposed to the
      type of outcomes that provide hard end points or factual data and can be easily
      defined quantitatively. The softness of QOL outcomes relative to survival and
      tumor response is cited as a particular barrier to implementation and
      interpretation of results. This article reviews the importance of QOL to clinical
      practice, discusses the perceived softness of QOL, and compares the roles of
      symptoms and QOL scores as they relate to disease progression and tumor response.
      Providing sound QOL data to healthcare professionals and patients is essential to
      enable truly informed decision-making.

PMID- 12512982
TI  - The role of patient-reported outcomes in evaluating the quality of oncology care.
AB  - The science of oncology care is rapidly developing, resulting in considerable
      variation in treatment patterns and disparity in the quality of care. Efforts are
      under way to evaluate and improve the quality of oncology care, because the goals
      of care have progressed beyond reducing morbidity and mortality to include
      maximizing functional and cognitive status, improving health-related quality of
      life, and preserving productivity. Traditional indicators of quality of care were
      based on survival outcomes or the processes of care. Although these remain
      important, they are inadequate for evaluating the multidimensional goals of care.
      Although not commonly included, patient-reported outcomes (PROs) would enhance
      the evaluation of the quality of care by including a patient perspective. A model
      for measuring quality of care that incorporates outcomes, structures, and
      processes of care as well as patient characteristics is proposed. Methodology
      including PROs that are valid, reliable, sensitive, and feasible, as well as
      rigorous risk adjustment methods, is critical to quality of care studies that
      appropriately inform decision makers.

PMID- 12512983
TI  - New developments in oral care technology.

PMID- 12512984
TI  - Comparative clinical trials and the changing marketplace for oral care:
      innovation, evidence and implications.
AB  - The development of a trayless bleaching system (Crest Whitestrips) and a novel
      battery-powered toothbrush (Crest SpinBrush) has fueled growth in the bleaching
      and power toothbrush markets. Beyond offering convenient, low-cost options for
      patients, the effectiveness of each product is supported by a robust clinical
      program. New comparative research involving these products expands evidence on
      the clinical meaningfulness of the benefits of this whitening system and powered
      toothbrush for patient care.

PMID- 12512985
TI  - Objective and subjective whitening response of two self-directed bleaching
      systems.
AB  - PURPOSE: To evaluate objective and subjective whitening responses of two marketed
      vital bleaching systems under intended use conditions. MATERIALSA ND METHODS: The
      randomized clinical trial evaluated 50 adults who received either a combination
      system with a 3% hydrogen peroxide bleaching gel, pre-formed dual arch tray,
      dentifrice and oral rinse (Rapid White), or 6% hydrogen peroxide whitening strips
      (Crest Whitestrips). Efficacy was assessed objectively from L*a*b* tooth color at
      Days 7 & 14, while subjective, first-person whitening perception was measured by
      questionnaire. A cumulative multinomial probability model was generated to
      predict subjective responses from objectively measured tooth color. RESULTS: At
      end-of-treatment, adjusted mean deltab* was -2.05 +/- 0.158 for the whitening
      strip group compared to -0.69 +/- 0.141 for the combination group, with these
      groups differing significantly (P < 0.0001). This response held across every
      color parameter and time point in this study. Relative to the combination system,
      subjects in the whitening strip group rated that product significantly (P < 0.01)
      more favorably with respect to the amount of whiteness improvement, as well as
      whitening satisfaction and overall impression. These subjective responses were
      correlated with objective changes in tooth color measured during treatment. When
      the deltab* effect was included in a cumulative multinomial probability model,
      deltaL*, deltaa*, and treatment were non-significant predictors. Odds ratios
      demonstrate that a subject had 3.3 times (1/0.3003 = 3.33) greater odds of
      selecting a higher whiteness rating when the value of deltab* was decreased by
      1.0 unit (less yellowness). Similar results were noted for whitening satisfaction
      and overall impression of treatment.

PMID- 12512986
TI  - Vital bleaching with two at-home professional systems.
AB  - PURPOSE: To compare the whitening effectiveness of two professional vital
      bleaching systems in a randomized clinical trial. MATERIALS AND METHODS:
      Balancing for baseline color, 6 9 adult volunteers were randomized to either a
      whitening strip containing 6.5% hydrogen peroxide (Professional Crest
      Whitestrips) or a custom tray-based system using both hydrogen and carbamide
      peroxide (Nite White Excel2). Total contact time was 21 hours for the strip
      system and 28 hours for the 10% carbamide peroxide equivalent tray system.
      Whitening response was measured objectively as L*a*b* from digital images of the
      maxillary anterior teeth. RESULTS: Both treatments resulted in significant (P <
      0.01) improvements in yellowness (deltab*), brightness (deltaL*) and overall
      color (deltaE*). For between group comparisons, strip subjects had a
      statistically significant or directionally favorable whitening response relative
      to the tray system at intermediary time points, while at the end-of-treatment,
      the strip group had highly statistically significant (P < or = 0.005), superior
      whitening response for all color parameters measured in the study. Both
      treatments were generally well tolerated, with 35-40% of the subjects in each
      group reporting minor tooth sensitivity or gingival irritation.

PMID- 12512987
TI  - Comparative response of whitening strips to a low peroxide and potassium nitrate
      bleaching gel.
AB  - PURPOSE: To evaluate the clinical response of a low peroxide concentration
      bleaching system with a desensitizing agent relative to a marketed control.
      MATERIALS AND METHODS: After balancing for baseline color and age, 34 healthy
      adult volunteers were randomized to one of two marketed bleaching systems, 5%
      carbamide peroxide bleaching gel + potassium nitrate in a custom tray (Colgate
      Platinum Gentle Plus) or 6.0% hydrogen peroxide bleaching strips (Crest
      Whitestrips). Daily contact time was 6-8 hours for the tray system compared to 1
      hour for the strip system, following manufacturers' instructions. Whitening was
      measured objectively using digital image analysis to assess L*a*b* after 7 days,
      while tolerability was assessed through interview and examination. RESULTS: The
      predominantly female (85%) and non-smoking (91%) study population ranged from 20
      47 years of age. Both treatments yielded a statistically significant (P < 0.001)
      whitening benefit with respect to reduction in yellowness (Ab*) and improvements
      in other color endpoints (deltaL*, deltaE*, and a new parameter, deltaW*)
      compared to baseline. The strip group experienced greater color improvement on
      average for all color parameters in the study. After 7 days treatment, the
      adjusted mean deltab* was -1.24 in the strip group and -0.65 in the tray group,
      with these groups differing significantly (P = 0.04). Tooth sensitivity was
      reported by 13% of subjects using the hydrogen peroxide strips, compared to 22%
      of subjects using the carbamiide peroxide potassium nitrate tray system. No
      subjects discontinued treatment early due to an adverse event.

PMID- 12512988
TI  - Dental plaque removal with two battery-powered toothbrushes.
AB  - PURPOSE: To compare the plaque removal efficacy of a positive control power
      toothbrush (Colgate Actibrush) to an experimental power toothbrush (Crest
      SpinBrush) following a single use. MATERIALS AND METHODS: This study was a
      randomized, controlled, examiner-blind, 4-period crossover design which examined
      plaque removal with the two toothbrushes following a single use in 39 completed
      subjects. Plaque was scored before and after brushing using the Turesky
      Modification of the Quigley-Hein Index. RESULTS: Baseline plaque scores averaged
      2.18 and 2.16 for the experimental toothbrush and control toothbrush treatment
      groups, respectively. With respect to all surfaces examined, the experimental
      toothbrush delivered an adjusted (via analysis of covariance) mean difference
      between baseline and post-brushing plaque scores of 0.66 while the control
      toothbrush delivered an adjusted mean difference of 0.43. This represents an
      increase of 55% plaque removal relative to the control power toothbrush. The
      difference between brushes was statistically significant (P < 0.001). With
      respect to buccal and lingual surfaces, the experimental toothbrush delivered
      very consistent results relative to the control toothbrush. The differences
      between brushes were also statistically significant (P < 0.001).

PMID- 12512989
TI  - Plaque removal efficacy of a battery-operated power toothbrush compared to two
      control manual toothbrushes in single use studies.
AB  - PURPOSE: Recently, a power toothbrush (Crest SpinBrush) has been reported to
      remove plaque more effectively than a manual toothbrush (Colgate Navigator). The
      objective of these studies was to compare the plaque removal efficacy of two
      control manual toothbrushes (Colgate Wave and Colgate Plus) to an experimental
      power toothbrush (Crest SpinBrush). The Colgate Plus has an ordinary flat bristle
      trim design, while the Colgate Wave has an advanced design multilevel bristle
      trim for greater interproximal penetration. MATERIALS AND METHODS: Each of these
      two studies were randomized, controlled, examiner-blind, 4-period crossover
      designs which examined plaque removal with the experimental toothbrush relative
      to a control manual toothbrush following a single use in 37 and 35 subjects,
      respectively. Plaque was scored before and after brushing using the Turesky
      Modification of the Quigley-Hein Index. RESULTS: In the first study, average
      baseline plaque scores were 2.88 and 2.89 for the experimental toothbrush and
      advanced designed manual control toothbrush (Colgate Wave) treatment groups,
      respectively. With respect to all surfaces examined, the experimental toothbrush
      delivered an adjusted (via analysis of covariance) mean difference between
      baseline and post-brushing plaque scores of 0.70 while the control toothbrush
      delivered an adjusted mean difference of 0.59. The difference between the brushes
      was statistically significant (P < 0.001). The experimental toothbrush removed,
      on average, 19.9% more plaque than the control toothbrush. In the second study,
      baseline plaque scores averaged 3.07 and 3.04 for the experimental toothbrush and
      ordinary flat trim manual control toothbrush (Colgate Plus) treatment groups,
      respectively. With respect to all surfaces examined, the experimental toothbrush
      delivered an adjusted (via analysis of covariance) mean difference between
      baseline and post-brushing plaque scores of 0.87 while the control toothbrush
      delivered an adjusted mean difference of 0.62. The difference between brushes was
      statistically significant (P < 0.001). The experimental toothbrush removed, on
      average, 40.0% more plaque than the control toothbrush.

PMID- 12512990
TI  - Dental plaque removal efficacy of a battery-powered toothbrush vs. a control
      Japanese manual toothbrush.
AB  - PURPOSE: Recently, a new powered toothbrush has been marketed with a design that
      fundamentally differs from other marketed powered toothbrushes, in that it
      incorporates a round oscillating head, in conjunction with fixed bristles. The
      objective of this study was to compare the plaque removal efficacy of a control
      manual toothbrush (Lion Dentor Systema) to this experimental powered toothbrush
      (Crest SpinBrush) following a single use. MATERIALS AND METHODS: This study was a
      randomized, controlled, examiner-blind, 4-period crossover design which examined
      plaque removal with the two toothbrushes following a single use in 36 subjects.
      Plaque was scored before and after brushing using the Turesky Modification of the
      Quigley-Hein Index. RESULTS: Baseline plaque scores were 2.90 for the
      experimental toothbrush and 2.95 for the control toothbrush treatment groups.
      With respect to all surfaces examined, the experimental toothbrush delivered an
      adjusted (via analysis of covariance) mean difference between baseline and post
      brushing plaque scores of 0.70 while the control toothbrush delivered an adjusted
      mean difference of 0.54. The difference between treatment groups was
      statistically significant (P < 0.001). The experimental toothbrush removed, on
      average, 29.6% more plaque than the control toothbrush. With respect to buccal
      surfaces, the experimental toothbrush delivered an adjusted mean difference
      between baseline and post-brushing plaque scores of 1.09 while the control
      toothbrush delivered an adjusted mean difference of 0.90. This difference between
      treatment groups was also statistically significant (P = 0.001) and represents,
      on average, 21.1% more plaque removal with the experimental toothbrush. Results
      on lingual surfaces also demonstrated statistically significantly (P< 0.001)
      greater plaque removal for the experimental toothbrush with an average of 83.3%
      more plaque removal.

PMID- 12512991
TI  - N-acetylcysteine reduced the effect of ethanol on antioxidant system in rat
      plasma and brain tissue.
AB  - Chronic ethanol administration is able to induce an oxidative stress in the
      central nervous system. N-Acetylcysteine (NAC) has antioxidant properties; as a
      sulphydryl donor, it contributes to the regeneration of glutathione and it acts
      through a direct reaction with hydroxyl radicals. In this study we investigated a
      possible beneficial effect of NAC on some of the free radical related parameters.
      Twenty four male Wistar rats were divided in to three groups and were given
      ethanol (Group 1), ethanol and NAC (Group 2) and isocaloric dextrose (Group 3).
      Ethanol and NAC were given intragastrically at doses of 6 g/kg/day and 1
      g/kg/day, respectively. Our results show that chronic ethanol intake elicits
      statistically significant increase in MDA and NO levels and decrease in SOD and
      GSH levels in both plasma and brain (p < 0.001). GPx levels decreased in
      erythrocytes (p < 0.001). CAT activity showed significant decrease only in brain
      samples (p < 0.001). NAC administration effectively restores the above results to
      nearly normal levels. Therefore we suggest that reactive free radicals are, at
      least partly, involved in the ethanol-induced injury of brain cells and NAC
      mitigate the toxic effects of ethanol on the oxidant-antioxidant system of rat
      plasma and brain.

PMID- 12512992
TI  - Dobutamine induced dynamic left ventricular outflow tract obstruction in patients
      with hypertrophic nonobstructive cardiomyopathy.
AB  - Some patients with hypertrophic nonobstructive cardiomyopathy (HNCM) suffer
      symptoms resembling those in obstructive type despite no left ventricular outflow
      tract (LVOT) gradient could be detected on resting echocardiography. To
      investigate the value of dobutamine stress echocardiography (DSE) in determining
      the dynamic left ventricular (LV) obstruction of patients with HNCM. The study
      was conducted on 31 patients who were diagnosed HNCM on resting echocardiography
      and 9 healthy person as a control group. Intraventricular flow acceleration of >
      3 m/sec on DSE was accepted as dynamic LVOT obstruction. Group 1 and 2 included
      patients without and with dynamic LVOT obstruction, respectively. The occurrence
      of chest pain and dyspnea seen during DSE was more frequent in group 2 than group
      1 and control group. The frequency of SAM was significantly higher (p < 0.05) and
      the septal angle was significantly lower (p < 0.001) in Group 2. The presence of
      SAM significantly correlated with the peak gradient (r = 0.61, p < 0.001). The
      septal angle had significant negative correlations with the peak gradient (r = 
      0.77, p < 0.001) reached at DSE. The relative risk for peak gradient was highest
      when septal angle was < or = 100 degrees, with a sensitivity of 93%, specificity
      of 80%, positive predictive value of 82%, negative predictive value of 92%, and
      predictive accuracy of 87%. DSE is a reliable tool for the diagnosis of dynamic
      LV obstruction in patients with HNCM. The presence of SAM together with a low
      septal angle is highly predictive for the presence of a dynamic LVOT obstruction
      detected by DSE.

PMID- 12512993
TI  - Application of mutation analysis for the previously uncertain cases of adult
      onset type II citrullinemia (CTLN2) and their clinical profiles.
AB  - Type II citrullinemia (CTLN2) is characterized by a deficiency of
      argininosuccinate synthetase (ASS) in the liver. Mutation analysis of the
      SLC25A13 gene, which is responsible for CTLN2, provides a rapid and accurate
      diagnosis. We describe clinical, biochemical and histologic features of two
      patients, whose diagnosis was finally made by mutation analysis. They initially
      presented with symptoms related to hyperammonemia at 16 to 22 years of age. A
      patient had shown mental retardation and growth failure from early childhood.
      Laboratory findings including amino acids, were characteristic, such as elevated
      citrulline, arginine, and lysine concentrations, but definitive diagnosis had not
      been made. The patients died of liver cirrhosis and hepatoma at 31 and 34 years
      old, respectively. Fatty change in the hepatocytes was commonly observed in the
      autopsied specimens. ASS activity was decreased in the liver of both patients,
      and a concomitant decrease of arginase activity was found in one case.
      Investigation for the SLC25A13 mutation revealed that one patient was homozygous
      for IVS11 + 1G>A, and the other was compound heterozygote (851del4/S225X).
      Comparison of genetic, enzymatic and biochemical data among various cases of
      CTLN2 will be essential to understand the real nature of the disease.

PMID- 12512994
TI  - The effect of folic acid, vitamin B6 and vitamin B12 on the homocysteine levels
      in rabbits fed by methionine-enriched diets.
AB  - Atherosclerosis is an important cause of cardiovascular morbidity and mortality
      in recent years. Hyperhomocysteinemia is recognized as an independent risk factor
      for premature atherosclerosis and venous thrombosis. It is suggested that
      administration of folic acid, vitamin B6 and vitamin B12 may decrease
      homocysteine levels. In our study, we induced hyperhomocysteinemia in rabbits by
      giving methionine and studied the effects of folic acid, vitamin B6 and vitamin
      B12 on homocysteine levels. A total of 40 (20 female, 20 male New Zealand
      rabbits) were divided into four groups, each consisting of 10 rabbits. Methionine
      (100 mg/kg/day), methionine (100 mg/kg/day) plus vitamin B6 (30 mg/kg/day),
      methionine (100 mg/kg/day) plus vitamin B12 (80 mg/kg/day) and methionine (100
      mg/kg/day) plus folic acid (20 mg/kg/day) were given to the first, second, third
      and forth groups respectively. These rabbits were followed up for two months. We
      studied homocysteine levels on the 0, 20th, 40th and 60th days in all groups. In
      rabbits we induced hyperhomocysteinemia by giving methionine for 2 months. The
      decreases of homocysteine levels in the forth group were significant with respect
      to the second and third groups. Folic acid supplementation clearly resulted in a
      reduction of plasma homocysteine levels, whereas vitamin B12 was little effective
      and vitamin B6 failed to show an effect. We conclude that even folic acid
      treatment alone may be sufficient for decreasing negative effects of
      homocysteine.

PMID- 12512995
TI  - Post-endsystolic active shortening in the non-ischemic region impairs left
      ventricular pressure fall in acute ischemic heart.
AB  - To investigate the relation between the impairment of isovolumic relaxation and
      the regional wall motion in acute ischemia, the left ventricular pressure fall
      and regional myocardial motion were examined in the relaxation phase in dogs
      during both acute coronary artery occlusion (n = 12) and a regional coronary flow
      reduction (n = 6). Fifteen to 40 seconds after complete coronary artery occlusion
      or in the stable state after a regional coronary flow reduction by 70 to 90% of
      the control state, a shortening of the non-ischemic region at the early
      isovolumic relaxation phase (the post-endsystolic shortening) appeared, combined
      with lengthening of the ischemic region. In these situations, the logarithmic
      plots of the left ventricular pressure fall was composed of two components (time
      constant of early part [Ta] and at latter part [Tb]). Ta was greater than Tb
      (64.3 +/- 13.8 milliseconds vs. 36.6 +/- 10.4 milliseconds at 15 seconds after
      coronary occlusion, p < 0.01; 67.6 +/- 22.9 milliseconds vs. 45.1 +/- 17.5
      milliseconds at flow reduction, p < 0.01) and the time constant at control (p <
      0.01). These findings suggested that post-endsystolic shortening in the non
      ischemic region played a role in a the non-uniformity of the left ventricular
      contraction and contributed to the impairment of the left ventricular pressure
      fall in acute regional ischemia, especially in early isovolumic relaxation.

PMID- 12512996
TI  - A novel stop codon mutation (X465Y) in the argininosuccinate lyase gene in a
      patient with argininosuccinic aciduria.
AB  - Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is a rare autosomal
      recessive disorder affecting the urea cycle. The cardinal symptom in the neonatal
      form is progressive hyperammonemia, which is often life-threatening. However,
      clinical symptoms in the late onset form are quite heterogeneous. As well as
      measurement of ASL activity, analysis of the ASL gene is necessary to clarify the
      genetic basis of various phenotypes. We report a patient with late onset
      argininosuccinate lyase deficiency (ASLD) who had hepatomegaly and mildly
      increased level of ammonia. By mutation analysis of the mRNA and genomic DNA from
      the patient's leukocytes, we identified a novel missense mutation 1395G>C in the
      homozygous state, which results in the exchange of a stop codon to tyrosine at
      amino acid position 465 (X465Y). This unique mutation causes an elongation of
      fifty amino acids in the C-terminal region of the ASL protein, and is likely
      related to a milder phenotype compared with previously reported mutations. In
      addition, this is the first report on mutation analysis in a Japanese ASLD
      patient.

PMID- 12512997
TI  - Sulfite is generated from PAPS by activated neutrophils.
AB  - We previously reported that neutrophils produce sulfite in response to
      stimulation with lipopolysaccharide, and sulfite production is dependent on
      inorganic sulfate contained in culture media. Microorganisms such as yeast
      assimilate sulfate, during which process sulfite is generated by reduction of 3'
      phosphoadenosine 5'-phosphosulfate (PAPS), an activated sulfate donor. However,
      little is known about how sulfite is produced in mammalian cells. In the current
      study, we demonstrated that chlorate, a specific inhibitor for PAPS synthesis,
      significantly suppressed production of sulfite by activated neutrophils obtained
      from rat peritoneal cavity that had been injected with glycogen to induce
      inflammation. Addition of excess amounts of PAPS could partially overcome the
      inhibitory effect of chlorate. Moreover, sulfite production from PAPS was clearly
      demonstrated in the cytosolic fraction of activated neutrophils. These findings
      strongly suggest that sulfite is generated, at least in part, from PAPS by
      activated neutrophils.

PMID- 12512998
TI  - A case of lymphoepithelioma-like carcinoma arising from the palatine tonsil.
AB  - Lymphoepithelioma is the designation that has been given to describe
      undifferentiated squamous cell carcinoma variants of nasopharyngeal neoplasms
      (World Health Organization type 3), and a strong association with Epstein-Barr
      virus (EBV) infection has been established. Outside the nasopharynx,
      lymphoepithelioma-like carcinomas (LEC) are exceedingly rare in other head and
      neck lesions. This report features a rare case of LEC of the palatine tonsil
      occurring in a 60-year-old Japanese man who presented with a three-month history
      of a neck mass. The surface of tonsils were smooth, not ulcerated
      macroscopically, and the ipsilateral tonsil showed only slight enlargement on
      radiological findings. Diagnosis of lymphoepithelioma was finally made based on
      the pathological review of the tonsillectomy specimens, preceded by a cervical
      lymph node biopsy. The patient was treated with irradiation and adjuvant
      chemotherapy. RNA in situ hybridization as well as polymerase chain reaction
      (PCR) techniques, and serological testing did not demonstrate an association with
      EBV infection. The clinical presentation, pathological features and association
      with EBV are described with a review of the literature.

PMID- 12512999
TI  - Dental practice patterns add to oral health disparity.

PMID- 12513000
TI  - Dentists famous in other fields.
AB  - The profession of dentistry has long attracted individuals who were often multi
      talented, achieving fame in fields other than dentistry, such as literature,
      business, sports, and politics. Several have been justly rewarded with worldwide
      recognition. Many of these outstanding individuals continued to practice their
      profession while carrying on their avocation, while others decided to devote
      their entire time to the pursuit of these interests. Nevertheless, many in the
      dental profession are unaware of their colleagues who have achieved fame in other
      fields. Only a very few of these outstanding dentists are discussed in this
      article.

PMID- 12513001
TI  - Debt and practice profiles of beginning dental practitioners.
AB  - Escalating student debt for dental education has led some to speculate that
      beginning practitioners may undertake procedures that are beyond their competence
      in an effort to augment practice income. This hypothesis was tested directLy
      using a data set containing self-reports of practice profiles across a wide range
      of procedures and debt for education, practice, and personal purposes.
      Respondents were 113 individuals who had graduated from a private dental school
      from 1986 to 1997. Conservative dental practice was measured by comparing
      frequency of commonly and uncommonly performed procedures in the group as a whole
      against the profile for each respondent. There was no association between
      educationaL debt and propensity to engage in unconventional procedures. Older
      dentists and those who felt more competent at the time of graduation were less
      conservative. Amount of practice debt was a better predictor of unconventional
      practice than was educational debt.

PMID- 12513002
TI  - George Franklin Grant, DMD: renaissance man.
AB  - While George Franklin Grant may be known as the second African American dental
      graduate and the inventor of the golf tee, it is not generally known that he was
      one of the pioneers in cleft palate and speech therapy, a longtime faculty member
      of Harvard University's dental school, and the founder of the Harvard
      Odontological Society.

PMID- 12513003
TI  - Dumbing down of America.

PMID- 12513004
TI  - The changing face of research ethics.

PMID- 12513005
TI  - Anti-tumour necrosis factor therapy for severe inflammatory arthritis: two years
      of experience in Northern Ireland.
AB  - Etanercept and infliximab are novel biological agents targeted against tumour
      necrosis factor alpha (TNFalpha), a key cytokine in the pathogenesis of
      rheumatoid arthritis (RA). We report the results of their use over a two year
      period in 94 patients with severe inflammatory arthritis. Eighty-eight adults
      with active inflammatory arthritis (82 with RA), unresponsive to all conventional
      treatment, received biological therapy in one of five specialist centres in
      Northern Ireland. 69 adult patients (78%) had a good response to treatment, four
      a partial response, and seven no response. The results of treatment could not be
      assessed in eight patients because they had only recently commenced therapy. Four
      patients had a mild allergic reaction to treatment but one patient developed
      fulminant lung fibrosis which may have been due to drug therapy and eventually
      proved fatal. There were four cases of major infection requiring hospitalisation.
      Two patients responded to treatment, but one succumbed to bacterial pneumonia,
      and another to bacterial meningitis. Six children with juvenile idiopathic
      arthritis (JIA) received etanercept. Four achieved a good response, one a partial
      response, and one no response to treatment. This study shows that the impressive
      response to anti-TNF therapies extends beyond the realm of clinical trials to
      everyday clinical practice. These agents represent a major advance in the
      treatment of severe inflammatory arthritis but they should be used with caution,
      particularly in the elderly and in patients who are predisposed to infection.

PMID- 12513006
TI  - Management of symptomatic liver cysts.
AB  - Non-parasitic liver cysts are seen in up to 5% of the population. They become
      symptomatic when they are large and can cause pain, nausea, vomiting, early
      satiety and obstructive jaundice. Treatment modalities include percutaneous
      drainage, open deroofing, hepatic resection and lately, laparoscopic deroofing.
      We assessed our management of eleven symptomatic patients over the last five
      years between May 1996 and August 2001. Two of these had mild symptoms and were
      kept under review. The remaining nine were treated surgically. Of these, eight
      were treated by laparotomy and open deroofing with argon laser coagulation of the
      cut edges while one was treated with left hepatic resection. Three of these had
      been previously treated with laparoscopic deroofing at other hospitals and had
      been referred after having developed recurrent symptomatic cysts. Two patients
      developed post-operative complications--bile leakage that resolved with
      conservative management. The patients were followed up for a median period of
      twelve months ranging from 3-62 months. One patient died of liver failure 12
      months after surgery. There was no symptomatic recurrence. We conclude that open
      cyst deroofing gives marked symptomatic relief with a very low complication rate.
      In today's era of laparoscopic surgery, it has a definite role in the management
      of symptomatic liver cysts, more so in recurrent cysts following laparoscopic
      treatment.

PMID- 12513007
TI  - Treating Ulster's rural poor: the county infirmaries of Armagh and Down 1766
      1851.
AB  - This paper considers the role of county infirmaries in providing health care for
      the inhabitants of two counties in south-east Ulster. It traces the establishment
      and management of these institutions from their beginnings shortly after the
      passing of the Infirmaries Act (1765) to the middle of the nineteenth century.
      From the available evidence, the accommodation, staff, patient numbers and diet
      of the infirmaries are considered and an assessment of their efficacy in offering
      a valuable service to their communities is discussed.

PMID- 12513008
TI  - Transduodenal excision of ampullary tumours.
AB  - The commonly recommended treatment for ampullary tumours--pancreaticoduodenectomy
      results in significant morbidity and mortality. This study is a retrospective
      evaluation of the procedure of transduodenal local excision of ampullary tumours.
      Demographics, symptoms, histological findings and outcomes were retrospectively
      analysed in 15 patients. Survival analysis was done by the method of Kaplan-Meier
      and log-rank test. The median age was 68 years (range 54-78). Endoscopic biopsy
      was accurate in only 41% of cases. CT scan demonstrated a mass in 50% cases.
      Definitive histology reported 4 adenomas, 2 carcinomas-in-situ and 9
      adenocarcinomas. Median hospital stay was 13 days. There was no operative
      mortality. Mean duration of follow-up was 31 months (range 7-70 months). The
      procedure appears curative for adenomas and in-situ carcinoma. Overall 3 year
      actuarial survival for ampullary tumours is 65% while that for moderately
      differentiated carcinomas is 50%. Pre-operative investigations provide inadequate
      histological information. Wide local excision is a safe operation with low
      morbidity and good survival in carefully selected cases. However, the role of
      local excision for carcinoma appears to be palliative rather than curative.

PMID- 12513009
TI  - Gall bladder cancer--radical surgery, the key role to improve outcome.

PMID- 12513010
TI  - Milk alkali syndrome.

PMID- 12513011
TI  - Coeliac disease presenting with colonic lymphoma.

PMID- 12513012
TI  - Intestinal obstruction following blunt abdominal trauma.

PMID- 12513013
TI  - "Bird fancier's mouth", an unusual case of obstructive sialadenitis.

PMID- 12513014
TI  - Perforation of the sigmoid colon secondary to localised amyloidosis.

PMID- 12513015
TI  - Histoplasmosis as a presentation of human immunodeficiency virus infection.

PMID- 12513016
TI  - The Chinese drinking problem: a review of the literature and its implication in a
      cross-cultural study.
AB  - Alcoholism as a problem has never been widely understood in Chinese society. The
      rarity of alcoholism in Chinese society may be due to marked sensitivity to
      alcohol, associated with high levels of acetaldehyde, in this population. In
      addition, sociocultural reasons such as alcoholic beverages generally being
      consumed only at parties and during mealtimes, strong social sanctions against
      drunkards and drunken behavior, and the presence of a strong Confucian moral
      ethic, have accounted for the drinking behavior of Chinese individuals. However,
      there is evidence that alcohol consumption and the prevalence of alcoholism have
      skyrocketed in the past 40 years in Taiwan. Social and cultural changes may be
      expected to affect the incidence and prevalence of alcoholism and other mental
      disorders in terms of changes in a traditional culture, and social integration
      disintegration. Differences in methodology for case identification, and the fact
      that Chinese alcoholic patients do not seek psychiatric treatment primarily for
      drinking problems, are also considered to account for some of the discrepancy
      between the actual rate and the lower identified rate of alcoholism. It can also
      be speculated that the low rate of alcoholism in psychiatric settings depends
      largely on the attitudes of patients, their families, and the general public
      towards drinking problems. Hence, this paper will review the theories and compare
      epidemiologic data about drinking problems in Chinese individuals, and then point
      to areas for future research.

PMID- 12513017
TI  - Paraoxonase activities in Minnan and Hakka.
AB  - Three phenotypes of paraoxonase (PON) have been found in population studies. The
      B type gene frequency varies among different populations. The Singaporean Chinese
      gene frequency is trimodal. The gene frequency of British Chinese populations was
      neither bimodal nor trimodal. We conducted a study to determine the frequency
      distribution of PON in the Minnan and Hakka populations. We collected blood
      samples and questionnaires from Minnan and Hakka subjects from Nantou County,
      Taiwan, excluding those with PON confounding factors. The blood samples were then
      examined for PON-non-NaCl (PON without salt stimulation), PON-NaCl (PON with salt
      stimulation) and arylesterase activities. We compared median differences in age,
      sex, PON-non-NaCl, PON-NaCl, arylesterase, and PON-NaCl/arylesterase between
      Minnan and Hakka populations using chi-square and rank analysis of variance
      (ANOVA), adjusted for age. There were 258 Minnan and 67 Hakka subjects without
      confounding factors. None of the frequency distributions for PON-non-NaCl, PON
      NaCl, or PON-NaCl/arylesterase was clearly bimodal or trimodal. Hakka were older
      and had increased PON-non-NaCl, PON-NaCl, and PON-NaCl/arylesterase when compared
      with Minnan, but only age and PON-non-NaCl were significantly different. Hakka
      and Minnan may have more heterozygous AB phenotype for PON, which might explain
      why the frequency distribution is not trimodal or bimodal. Marriage among Minnan,
      Hakka, Aborigines, and other Mainland Chinese in Taiwan may be responsible for
      difficulty in differentiating gene frequencies among subpopulations by PON
      phenotype. Nonetheless, the Hakka appeared to have greater PON activity than the
      Minnan. Subpopulation in itself may be a factor for higher PON activity among the
      Hakka after controlling for confounding factors.

PMID- 12513018
TI  - A preliminary study on the health promotion outcomes of high-risk hypertensive
      freshmen.
AB  - This preliminary study identified the outcomes of a health promotion program
      encompassing health education (2 hours) and case management for 4 weeks applied
      to high-risk hypertensive freshmen (systolic blood pressure, > or = 160 mmHg, or
      diastolic blood pressure > or = 100 mmHg) at a university located in Southern
      Taiwan. Twenty-two freshmen participated and data were collected at baseline and
      4 weeks later, after the program. Outcome indicators included biologic (blood
      pressure, body weight and body fat composition) and healthy lifestyle
      characteristics (assessed using the Health Promotion Lifestyle Profile [HPLP] and
      case management documentation). The Wilcoxon signed rank test showed that
      systolic blood pressure, body weight, and four subscales of the HPLP, health
      responsibility, interpersonal support, nutrition, and exercise, had improved
      significantly. This program could be used as a reference to refine further health
      promotion programs in the university.

PMID- 12513019
TI  - Lamotrigine-related skin rashes in adults.
AB  - Skin rash is a common adverse effect of lamotrigine (LTG) in both add-on and
      monotherapy trials and is also the most common adverse event causing LTG
      withdrawal. From our series of 254 prospectively registered adult patients
      treated with LTG at a dosage of 25-100 mg/ day, the incidence of allergic and non
      allergic skin reactions was 5.1% (13/254) and 1.9% (5/254), respectively.
      Meanwhile, the rate of allergic skin rashes causing LTG withdrawal was 3.9%
      (10/254). Co-medication with valproic acid (9.1%) resulted in a higher risk than
      co-medication with enzyme-inducing antiepileptic medications (2.8%). Moreover,
      another risk factor was higher initiation and relatively rapid dosage escalation.
      Among the 13 patients with allergic skin reaction, skin rash appeared during the
      initiation phase in 12 patients. All the allergic skin lesions were mild, except
      one presenting with Stevens-Johnson syndrome (0.4%). The patient was an 85-year
      old female treated with LTG monotherapy. Three of 13 patients with allergic skin
      responses were maintained on LTG with concomitant use of anti-allergic
      medications, and their rashes gradually disappeared. Another three patients
      agreed on rechallenge with LTG with a smaller dose of no more than 12.5 mg/day
      after the disappearance of their skin rashes and there was no recurrence of
      allergic reaction. In conclusion, the incidence and risk factors of LTG-related
      skin rashes in the present study of adults with epilepsy were comparable to
      findings from clinical trials in Western countries.

PMID- 12513020
TI  - DKC1 gene mutation in a Taiwanese kindred with X-linked dyskeratosis congenita.
AB  - Dyskeratosis congenita (DKC) is a rare inherited disease characterized by the
      triad of abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia.
      Recent studies demonstrated mutations in the DKC1 gene encoding a protein named
      dyskerin, which is a component of human telomerase. In addition to the
      hypothesized function of pseudouridination in rRNA biosynthesis, ribosomal
      subunit assembly, and/or centromere/ microtubule binding, lower levels of
      telomerase activity in cells from patients with X-linked DKC have been observed.
      We report the mutation analysis of a Taiwanese family with X-linked DKC. The
      patient was a 19-year-old man who presented with progressive reticulate
      hyperpigmentation, nail dystrophy, alopecia, leukoplakia of the tongue, and
      pancytopenia. He died of enterocolitis and Escherichia coli sepsis at the age of
      20 years. Only his mother's DNA was available for mutation analysis, which
      revealed a nucleotide transition of C to T (1058 C --> T), a hotspot mutation in
      DKC, resulting in an amino acid change from alanine to valine (A353V) in the DKC1
      gene. Recent advances in the research of telomerase and its implications in the
      human aging process and cancer are discussed.

PMID- 12513021
TI  - Bleeding duodenal varices after gastroesophageal varices ligation: a case report.
AB  - Duodenal varices are rarely occurring sites of hemorrhage in patients with portal
      hypertension, and such hemorrhaging can be a life-threatening event. We report
      the case of a 58-year-old woman with cirrhosis who presented with melena after
      successful ligation of gastroesophageal varices 1 week earlier. Upper
      gastrointestinal endoscopy revealed bleeding duodenal varices in the second
      portion of the duodenum, which was considered to be the source of the bleeding.
      Endoscopic injection sclerotherapy with histoacryl and lipiodol achieved
      successful hemostasis. Nonetheless, the sclerosant spread to the lungs via a
      portosystemic shunt, causing a pulmonary embolism. This is a rare complication
      seldom reported in the world literature.

PMID- 12513022
TI  - Nasopharyngeal carcinoma with skull base invasion and hydrocephalus: a case
      report.
AB  - We describe a case of nasopharyngeal carcinoma (NPC) with diffuse skull base bony
      destruction, resulting in obstructive hydrocephalus. Previously, these lesions
      were reported to be NPC with brain metastasis, without diffuse bony destruction
      of the skull base or hydrocephalus. We found no other cases of NPC with brain
      metastasis and diffuse bony destruction of the skull base resulting in
      hydrocephalus in the literature.

PMID- 12513023
TI  - Foreign-body-induced otitis media: a case report.
AB  - Unilateral ear discharge is one of the usual complaints of the patients who
      visited the otolaryngology clinics, especially those patients who suffered from
      external or middle ear disease. We present a 33-year-old female patient who
      suffered from persistent ear discharge of the left ear. The local findings showed
      a yellowish to greenish discharge and fetid odor from her left ear canal,
      occupied by a large amount of granulation tissue. Wide removal of the diseased
      granulation tissue and tympanoplasty were performed in the patient. Four pieces
      of cotton were found in the external auditory canal and middle ear cavity during
      the operation. For more than 2 years of follow-up at our clinic, the patient has
      had a dry ear and her hearing ability also improved. Foreign-body-induced otitis
      media in adults is very rare. Therefore, we present this rare case and review the
      reported literature so that the clinical symptoms and signs, imaging findings,
      clinical treatment, prognosis, and hearing change in foreign-body-induced otitis
      media may be recognized and understood.

PMID- 12513024
TI  - Endogenous nitric oxide synthesis differentially modulates pressure-flow and
      pressure-conductance relationships in the internal and external carotid artery
      circulations of the rat.
AB  - The role of endogenous nitric oxide (NO) synthesis was investigated in the
      regulation of the internal (ICA) and external carotid artery (ECA) beds of
      ventilated, anesthetized rats in a model in which the left common carotid artery
      was perfused from the aorta via an extracorporeal circuit under conditions of non
      pulsatile controlled flow. The territories supplied by the extracranial ICA and
      ECA were studied separately following occlusion of the appropriate artery. An
      inhibitor of nitric oxide synthesis, N(G)-monomethyl-L-arginine (L-NMMA), and the
      NO synthase substrate L-arginine were administered via a jugular venous catheter.
      NO synthesis exerted an important influence on the pressure-flow relationships of
      the ICA and ECA circulations as L-NMMA increased input perfusion pressure at any
      given flow rate. However, in the presence of NO synthesis, hydraulic conductance
      increased rapidly with flow in the ICA, thereby stabilizing perfusion pressures
      over a wide range of flow rates, whereas this phenomenon was not evident in the
      ECA territory. Differences between the two circulations were further emphasized
      by observations that L-arginine antagonized the systemic hemodynamic response to
      L-NMMA and its effects on the conductance of the ECA bed, whereas the effects of
      L-NMMA were irreversible in the ICA territory.

PMID- 12513025
TI  - Gross total removal of gliomas in the pulvinar and correlative microsurgical
      anatomy.
AB  - Tumors in the pulvinar tend to present as circumscribed lesions with exophytic
      growth into the lateral and third ventricles. These lesions may be best explored
      via a parietal-transcortical-transventricular approach. If the tumor extends
      posteriorly or inferiorly, a posterior-interhemispheric-transtentorial approach
      may provide a good angle of access. Gross total removal of the tumors in the
      pulvinar of two patients was achieved by surgical sectioning of the unilateral
      crus of the fornix or the splenium via a transventricular or interhemispheric
      approach with acceptable risk. These patients are now doing well as students
      about 6 years following the first operations. During tumor removal, a posterior
      interhemispheric-transtentorial approach combined with above-mentioned approaches
      was useful for orientation of the critical structures in the posterior incisural
      space. Knowledge of the anatomical relationships of the pulvinar to the crus of
      the fornix and the choroid plexus, and to the critical structures located in the
      posterior incisural space is extremely important for neurosurgeons.

PMID- 12513026
TI  - Bilateral cephalhematomas in a juvenile--case report.
AB  - A 14-year-old boy presented with subperiosteal cephalhematomas in bilateral
      parietotemporal sites after a minor head injury. Magnetic resonance (MR) imaging
      showed that one of the hematomas had progressed beyond suture lines, and spread
      under the temporal muscle layer. Progressive enlargement of the cephalhematomas
      occurred despite medical and needle aspiration treatment. Surgery found that the
      hematoma had separated the periosteum from the skull bone surface, and the
      periosteum had lost the tight attachment to the suture lines. Continuous suction
      drainage reduced the size of the hematomas without complications. MR imaging can
      identify subperiosteal cephalhematomas. The relationship of the hematoma and the
      temporal muscle may be the key MR imaging finding for the diagnosis of
      cephalhematoma. We suggest that some juvenile cephalhematomas may be a different
      clinical entity from those occurring in neonates.

PMID- 12513027
TI  - Cervical epidural hematoma after snowboarding injury--case report.
AB  - A 21-year-old man developed cervical spinal epidural hematoma one month after a
      snowboarding injury. He fell down while snowboarding and hit his occiput.
      Immediately after the injury, he suffered hypesthesic pain in the C-8 area
      associated with dull neck pain, which persisted for a month. Radiography of the
      cervical spine detected no pathological findings. The second attack of pain
      occurred when he was resting, followed by paraparesis and loss of urinary
      sensation within 24 hours. Emergent magnetic resonance (MR) imaging demonstrated
      an epidural hematoma at the levels of C-7 to T-2 which compressed the spinal
      cord. During the operation for removal of the hematoma, arterial rebleeding
      occurred from a small artery in the dural sac on the right C-8 root, which was
      thought to be responsible for the hematoma. The patient was discharged with no
      neurological deficits. Snowboarding-related injuries occur with higher frequency
      and involve greater risks compared to skiing-related injuries. Repeat MR imaging
      is strongly recommended to follow up any spinal injury, particularly in cases
      associated with focal neurological signs.

PMID- 12513028
TI  - Subdural hygroma as a complication of endoscopic neurosurgery--two case reports.
AB  - Two cases of subdural hygroma occurred in a series of 77 neuroendoscopic
      procedures. An 8-year-old boy underwent neuroendoscopic cysto-cisternostomy of a
      left temporal arachnoid cyst. Routine postoperative magnetic resonance imaging 7
      days later showed a large left-sided subdural hygroma without clinical symptoms.
      During the following 3 months, the subdural hygroma did not resolve
      spontaneously, so it was drained through a burr hole. A 3-month-old boy with
      aqueductal stenosis developed bilateral subdural hygromas after third
      ventriculostomy. Several punctures through the open anterior fontanelle relieved
      the hygromas but increasing head circumference required ventriculoperitoneal
      shunting 12 months later. Complications of neuroendoscopic procedures are
      increasingly reported, including various kinds of bleeding, infections, or damage
      of neuronal tissue. Only three previous cases of subdural hygroma or hematoma
      after neuroendoscopic interventions have been reported. The possible etiologies
      and clinical consequences of this rare complication have to be considered before
      selecting neuroendoscopy treatment.

PMID- 12513029
TI  - Dissecting basilar artery aneurysm growing during long-term follow up--case
      report.
AB  - A 58-year-old male presented with a dissecting aneurysm of the basilar artery
      manifesting as dysarthria, left hemiparesis, and numbness of the left side.
      Angiography revealed a double lumen at the midportion of the basilar artery which
      was consistent with a diagnosis of dissecting basilar artery aneurysm. The
      patient was treated conservatively, and remained neurologically stable for a 5
      year period following initial presentation, but serial magnetic resonance imaging
      revealed growth of the aneurysm compressing the brain stem. His condition then
      worsened. Computed tomography revealed obstructive hydrocephalus.
      Ventriculoperitoneal shunting was performed and the patient's symptoms improved.
      However, he died of subarachnoid hemorrhage. Autopsy showed the patient had had a
      type 3 "dolichoectatic dissecting aneurysm." Surgical treatment should be
      seriously considered for treating the patients with dissecting basilar artery
      aneurysm causing brain stem ischemia, especially if the aneurysm is growing. High
      flow bypass and proximal occlusion may be the choice in patients with poor
      collateral circulations.

PMID- 12513030
TI  - Facial nerve palsy after intracisternal papaverine application during aneurysm
      surgery--case report.
AB  - A 61-year-old woman suffered transient mydriasis and prolonged facial nerve palsy
      after intracisternal papaverine application subsequent to elective clipping of an
      unruptured middle cerebral artery aneurysm. The mydriasis resolved within 90
      minutes, but the facial nerve dysfunction persisted for 2 months before complete
      recovery. Prolonged irrigation of the cisterns may have washed the papaverine
      into contact with the facial nerve. This case supports previously reported
      evidence of a possible effect of topical intracisternal papaverine hydrochloride
      application on the facial nerve.

PMID- 12513031
TI  - Giant cell glioblastoma manifesting as traumatic intracerebral hemorrhage--case
      report.
AB  - A 33-year-old male presented with intracerebral hemorrhage in the left
      temporoparietal region after a traffic accident. Ten months later, the traumatic
      hemorrhage was found to originate in an underlying giant cell glioblastoma. Our
      case indicates that non-traumatic underlying pathologies, such as vasculopathies,
      coagulopathies, or tumors, should be considered in the differential diagnoses of
      intracerebral hemorrhage occurring in unusual locations after traumatic
      accidents.

PMID- 12513032
TI  - Peritoneal shunt migration into the pulmonary artery--case report.
AB  - A 48-year-old man underwent ventriculoperitoneal shunting for hydrocephalus
      secondary to subarachnoid hemorrhage due to left vertebral artery dissection,
      which had been successfully treated by trapping. The peritoneal catheter was
      correctly positioned via a right upper abdominal incision, and symptoms related
      to the hydrocephalus disappeared. One month later, the patient began to complain
      of pain on the right side of the neck. Chest radiography revealed that the
      peritoneal end of the catheter had migrated into the right pulmonary artery. The
      catheter route was explored through a small neck incision, and was found to enter
      the external jugular vein. The catheter was extracted and repositioned into the
      peritoneum. This type of shunt migration is quite unusual, but could be lethal by
      causing pulmonary infarction or arrhythmia. The catheter had probably entered the
      external jugular vein through a perforation caused by the shunt guide during the
      ventriculoperitoneal shunt operation. Follow-up radiography should be scheduled
      to detect such a complication.

PMID- 12513033
TI  - Thoracic intramedullary cysticercosis--two case reports.
AB  - A 36-year-old male and a 20-year-old male presented with intramedullary
      cysticercosis in the thoracic spinal cord. Magnetic resonance imaging clearly
      identified the cysts. Surgery was performed to decompress the spinal cord, as
      both patients had progressive and severe worsening of their neurological
      condition. Intramedullary cysticercosis can be treated successfully by surgery
      and/or medical therapy.

PMID- 12513034
TI  - The impact of salient role stress on trajectories of health in late life among
      survivors of a seven-year panel study: analyses of individual growth curves.
AB  - The purpose this study is twofold: 1) to model changes in health over time among
      older adults; and 2) to assess the degree to which stress arising in salient
      social roles accounts for individual variation in these changes. Individual
      growth curve analyses using Hierarchical Linear Modeling (HLM) software were
      employed with longitudinal data collected from a nationwide sample of 465 older
      adults between 1992-1999. The data suggest that, throughout the course of the
      study, the sample as a whole experienced linear deterioration in self-rated
      health. After accounting for the effects of non-salient role stress and
      demographic characteristics, variance in health changes was not accounted for
      significantly by salient role stress in an additive model. However, the inclusion
      of a multiplicative term showed that as respondent age increased, the association
      between salient role stress and adverse changes in health strengthened
      significantly. These results support the idea that the oldest-old may be
      particularly vulnerable to the effects of stress. This finding has important
      implications for targeting interventions and should stimulate further study
      regarding how and why responses to stress change progressively with age.

PMID- 12513035
TI  - Activity interests and Holland's RIASEC system in older adults.
AB  - Leisure activities are widely used in research to predict important outcomes, but
      the existing studies use different classification schemes and apparently rely on
      the intuition of the researcher to classify activities. The goal of the current
      study was to use the Holland RIASEC personality system to empirically classify
      activities using a sample of older adults. Nine activity scales were identified.
      The correlation of these activity scales with the Holland system showed that they
      could be reliably classified; further, multidimensional scaling suggested that
      the pattern of relationship could be interpreted in terms of the RIASEC hexagon.
      The overall findings suggest that Holland's RIASEC system may offer a useful way
      to classify many activities.

PMID- 12513036
TI  - Motivation, personality and well-being in older volunteers.
AB  - This study examined the effects of personality traits and motivation to volunteer
      on well-being as 107 older participants went through an intervention to increase
      volunteering. Three groups of volunteers, current, new, and former volunteers,
      participated. Participants were assessed four times on standardized measures of
      personality, health, motivation, and well-being: before and after a wait period,
      after volunteering, and at one year follow-up. There were no differences between
      pre, post and follow-up well-being. Regression analysis indicated that health,
      personality traits and motivation predicted well-being at pre-intervention. In
      contrast, after the intervention, regression analysis indicated that the
      interaction of higher neuroticism and greater motivation scores predicted lower
      well-being compared to other volunteers. One year follow-up results indicated
      that personality traits and health predicted well-being and that higher initial
      motivation predicted drop-outs while those continuing to volunteer increased
      their motivation scores.

PMID- 12513037
TI  - Influences of age and gender on workers' goals for retirement.
AB  - Having clear goals for retirement is a critical determinant of life satisfaction
      and adjustment during the post-employment transition period. The purpose of the
      present study was to explore individuals' goals for retirement and determine
      whether age and gender differences exist among those goals. A sample of 55
      working adults (aged 20-67) were asked to list their retirement goals. Items
      contained on respondents' lists were then classified into a taxonomy of
      retirement goals adapted from the work of LaPierre, Bastin, and Bouffard (1997).
      Both age and gender differences were identified in the concreteness of
      individuals' goals. Additionally, the number of retirement goals individuals hold
      decreased across the lifespan. Results also revealed patterns of age and gender
      differences across the various coding categories in the goal taxonomy. Findings
      are discussed in terms of the applied benefits of understanding the retirement
      goals of American workers.

PMID- 12513038
TI  - Glycemic effects of postmenopausal hormone therapy: the Heart and
      Estrogen/progestin Replacement Study. A randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Randomized trials of postmenopausal hormone therapy have found
      differing effects on fasting glucose levels. No trial has evaluated the effect of
      hormone therapy on diabetes incidence. OBJECTIVE: To evaluate the effect of
      hormone therapy on fasting glucose level and incident diabetes. DESIGN:
      Randomized, double-blind, placebo-controlled trial. SETTING: 20 U.S. clinical
      centers. PARTICIPANTS: 2763 postmenopausal women with coronary heart disease who
      were followed for 4.1 years. At baseline, 734 women had diabetes, 218 women had
      impaired fasting glucose, and 1811 women were normoglycemic; the 2029 women
      without diabetes were followed for incident diabetes. INTERVENTION: 0.625 mg of
      conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo.
      MEASUREMENTS: Fasting glucose level was measured at baseline, at year 1, and at
      the end of the trial. Incident diabetes was defined by self-report of diabetes or
      disease complication, fasting glucose level of 6.9 mmol/L or greater (> or =126
      mg/dL), or initiation of therapy with diabetes medication. RESULTS: Fasting
      glucose levels increased significantly among women assigned to placebo but did
      not change among women receiving hormone therapy. The incidence of diabetes was
      6.2% in the hormone therapy group and 9.5% in the placebo group (relative hazard,
      0.65 [95% CI, 0.48 to 0.89]; P = 0.006). The number needed to treat for benefit
      to prevent one case of diabetes was 30 (CI, 18 to 103). Changes in weight and
      waist circumference did not mediate this effect. CONCLUSIONS: In women with
      coronary disease, hormone therapy reduced the incidence of diabetes by 35%. This
      observation provides important insights into the metabolic effects of
      postmenopausal hormones but is insufficient to recommend the use of hormones for
      secondary prevention of heart disease.

PMID- 12513039
TI  - Systolic blood pressure, diastolic blood pressure, and pulse pressure as
      predictors of risk for congestive heart failure in the Framingham Heart Study.
AB  - BACKGROUND: Although hypertension is a principal precursor of congestive heart
      failure (CHF), the separate relations of systolic, diastolic, and pulse pressure
      with risk for heart failure have not been fully elucidated. OBJECTIVE: To examine
      the value of blood pressure predictors of heart failure. DESIGN: Community-based
      inception cohort study. SETTING: Framingham, Massachusetts. PATIENTS: 2040 free
      living Framingham Heart Study participants (mean age, 61 years [range, 50 to 79
      years]). MEASUREMENTS: The association of baseline systolic, diastolic, and pulse
      pressure with risk for incident CHF was examined in 894 men and 1146 women.
      Framingham Heart Study participants free of CHF at the baseline examination
      (performed from 1968 to 1973) were monitored for up to 24 years (mean, 17.4
      years) for new-onset heart failure. Cox proportional hazards models were used to
      adjust for age, sex, smoking, left ventricular hypertrophy, body mass index,
      diabetes mellitus, high-density lipoprotein cholesterol level, and heart rate;
      hazard ratios and 95% CIs for blood pressure variables were estimated. RESULTS:
      CHF developed in 234 participants (11.8%) during the follow-up period. All three
      blood pressure components were related to the risk for CHF, but the relation was
      strongest for systolic and pulse pressure. A 1-SD (20 mm Hg) increment in
      systolic pressure conferred a 56% increased risk for CHF (hazard ratio, 1.56 [95%
      CI, 1.37 to 1.77]); similarly, a 1-SD (16 mm Hg) increment in pulse pressure
      conferred a 55% increased risk for CHF (hazard ratio, 1.55 [CI, 1.37 to 1.75]).
      These associations were unrelated to age, duration of follow-up, and initiation
      of treatment for hypertension during follow-up; they were also observed in
      patients with systolic hypertension (systolic blood pressure > or = 140 mm Hg) at
      the baseline examination (hazard ratio, 1.41 [CI, 1.18 to 1.69] for pulse
      pressure and 1.42 [CI, 1.14 to 1.76] for systolic pressure). CONCLUSIONS:
      Although each component of blood pressure was associated with risk for CHF, pulse
      and systolic pressure conferred greater risk than diastolic pressure. Increased
      pulse pressure may help identify hypertensive patients at high risk for overt CHF
      who are candidates for aggressive blood pressure control.

PMID- 12513040
TI  - Genetic variation in the renin-angiotensin system and abdominal adiposity in men:
      the Olivetti Prospective Heart Study.
AB  - BACKGROUND: The renin-angiotensin system is involved in adipocyte growth and
      differentiation and possibly in adipose tissue metabolism. OBJECTIVE: To
      investigate the association of polymorphism in the angiotensin-converting enzyme
      (ACE) I/D gene, angiotensinogen M235T gene, and angiotensin II type 1 receptor
      A1166C gene with body mass index, body fat pattern, and obesity-associated
      hypertension. DESIGN: Cross-sectional longitudinal study. SETTING: The Olivetti
      factories in Marcianise and Pozzuoli, suburbs of Naples, Italy. PARTICIPANTS: 959
      adult men, 25 to 75 years of age. MEASUREMENTS: Renin-angiotensin system
      polymorphism, anthropometric indexes, blood pressure, and serum glucose and
      insulin levels. RESULTS: No association was detected between angiotensinogen or
      angiotensin II type 1 receptor gene polymorphism and anthropometric indexes or
      blood pressure. For ACE I/D polymorphism, significant age-genotype interaction
      was detected on cross-sectional observation; the relation of body mass index,
      waist circumference, and diastolic blood pressure to age was significantly
      greater in persons with the DD genotype than in those with the ID or II genotype.
      Overweight and abdominal adiposity were more common in men with the DD genotype,
      particularly among older participants (51.1% vs. 36.5% and 33.1% vs. 22.0%,
      respectively). Odds ratios were 1.82 (95% CI, 1.16 to 2.87) for overweight and
      1.76 (CI, 1.06 to 2.90) for abdominal adiposity. Among 314 untreated men first
      examined 20 years earlier, those with the DD genotype had greater age-adjusted
      weight gain (1.45 kg [CI, 0.12 to 2.78 kg]) and change in diastolic blood
      pressure (2.83 mm Hg [CI, 0.39 to 5.28 mm Hg]). The relative risk for overweight
      was 2.34 (CI, 1.32 to 4.15) among participants with the DD genotype versus those
      with the ID or II genotype. CONCLUSIONS: The ACE I/D polymorphism was a
      significant predictor of overweight and abdominal adiposity in men. DD
      homozygosity was associated with larger increases in body weight and blood
      pressure in aging persons, as well as with higher incidence of overweight.

PMID- 12513041
TI  - Obesity in adulthood and its consequences for life expectancy: a life-table
      analysis.
AB  - BACKGROUND: Overweight and obesity in adulthood are linked to an increased risk
      for death and disease. Their potential effect on life expectancy and premature
      death has not yet been described. OBJECTIVE: To analyze reductions in life
      expectancy and increases in premature death associated with overweight and
      obesity at 40 years of age. DESIGN: Prospective cohort study. SETTING: The
      Framingham Heart Study with follow-up from 1948 to 1990. PARTICIPANTS: 3457
      Framingham Heart Study participants who were 30 to 49 years of age at baseline.
      MEASUREMENTS: Mortality rates specific for age and body mass index group (normal
      weight, overweight, or obese at baseline) were derived within sex and smoking
      status strata. Life expectancy and the probability of death before 70 years of
      age were analyzed by using life tables. RESULTS: Large decreases in life
      expectancy were associated with overweight and obesity. Forty-year-old female
      nonsmokers lost 3.3 years and 40-year-old male nonsmokers lost 3.1 years of life
      expectancy because of overweight. Forty-year-old female nonsmokers lost 7.1 years
      and 40-year-old male nonsmokers lost 5.8 years because of obesity. Obese female
      smokers lost 7.2 years and obese male smokers lost 6.7 years of life expectancy
      compared with normal-weight smokers. Obese female smokers lost 13.3 years and
      obese male smokers lost 13.7 years compared with normal-weight nonsmokers. Body
      mass index at ages 30 to 49 years predicted mortality after ages 50 to 69 years,
      even after adjustment for body mass index at age 50 to 69 years. CONCLUSIONS:
      Obesity and overweight in adulthood are associated with large decreases in life
      expectancy and increases in early mortality. These decreases are similar to those
      seen with smoking. Obesity in adulthood is a powerful predictor of death at older
      ages. Because of the increasing prevalence of obesity, more efficient prevention
      and treatment should become high priorities in public health.

PMID- 12513042
TI  - A hospitalization from hell: a patient's perspective on quality.
AB  - Patients usually cannot assess the technical quality of their care; however,
      examining a hospitalization through the patients' eyes can reveal important
      information about the quality of care. Patients are the best source of
      information about a hospital system's communication, education, and pain
      management processes, and they are the only source of information about whether
      they were treated with dignity and respect. Their experiences often reveal how
      well a hospital system is operating and can stimulate important insights into the
      kinds of changes that are needed to close the chasm between the care provided and
      the care that should be provided. This article examines the case of a patient
      admitted for ankle arthrodesis due to severe hemophilia-related arthritis. The
      surgery was successful, but the hospital stay was marked by inefficiency and
      inconveniences, as well as events that reveal fundamental problems with the
      hospital's organization and teamwork. These problems could seriously compromise
      the quality of clinical care. Unfortunately, most of these events occur regularly
      in U.S. hospitals. Relatively easy and inexpensive ways to avoid many of these
      problems are discussed, such as reducing variability in non-urgent procedures and
      routinely asking patients about their experiences and suggestions for
      improvement.

PMID- 12513043
TI  - Towards complete and accurate reporting of studies of diagnostic accuracy: The
      STARD Initiative.
AB  - BACKGROUND: To comprehend the results of diagnostic accuracy studies, readers
      must understand the design, conduct, analysis, and results of such studies. That
      goal can be achieved only through complete transparency from authors. OBJECTIVE:
      To improve the accuracy and completeness of reporting of studies of diagnostic
      accuracy in order to allow readers to assess the potential for bias in the study
      and to evaluate its generalizability. METHODS: The Standards for Reporting of
      Diagnostic Accuracy (STARD) steering committee searched the literature to
      identify publications on the appropriate conduct and reporting of diagnostic
      studies and extracted potential items into an extensive list. Researchers,
      editors, methodologists and statisticians, and members of professional
      organizations shortened this list during a 2-day consensus meeting with the goal
      of developing a checklist and a generic flow diagram for studies of diagnostic
      accuracy. RESULTS: The search for published guidelines on diagnostic research
      yielded 33 previously published checklists, from which we extracted a list of 75
      potential items. The consensus meeting shortened the list to 25 items, using
      evidence on bias whenever available. A prototypical flow diagram provides
      information about the method of patient recruitment, the order of test execution,
      and the numbers of patients undergoing the test under evaluation, the reference
      standard, or both. CONCLUSIONS: Evaluation of research depends on complete and
      accurate reporting. If medical journals adopt the checklist and the flow diagram,
      the quality of reporting of studies of diagnostic accuracy should improve to the
      advantage of the clinicians, researchers, reviewers, journals, and the public.

PMID- 12513044
TI  - Update in gastroenterology.

PMID- 12513046
TI  - Prescribing oral contraceptives for women older than 35 years of age.
AB  - This paper addresses the use of combined oral contraceptives in women older than
      35 years of age, including the potential risks and benefits, pretreatment
      assessment, common side effects and their management, appropriate follow-up, and
      diagnosis of menopause. The case-based discussion also focuses on issues that
      pertain to women who smoke, have hypertension, or have dyslipidemia.

PMID- 12513047
TI  - CPR for patients labeled DNR: the role of the limited aggressive therapy order.
AB  - Patients who sustain a cardiac arrest have a less than 20% chance of surviving to
      hospital discharge. Patients may request do-not-resuscitate (DNR) orders if they
      believe that their chances for a meaningful recovery after cardiopulmonary arrest
      are low. However, in some identifiable circumstances, cardiopulmonary
      resuscitation (CPR) has a higher chance of success and lower likelihood of
      neurologic impairment. The probability of survival from a cardiac arrest
      influences patients' wishes regarding resuscitation; thus, when CPR has a higher
      likelihood of success, patients' expressed preferences for treatment as contained
      within a DNR order may not accurately reflect their intended goals. Patients
      should be offered the option of consenting to CPR for "higher-success"
      situations, including a witnessed cardiopulmonary arrest in which the initial
      cardiac rhythm is ventricular tachycardia or fibrillation, cardiac arrest in the
      operating room, and cardiac arrest resulting from a readily identifiable
      iatrogenic cause. This new level of resuscitation could be called a "limited
      aggressive therapy" order.

PMID- 12513048
TI  - Lower diabetes risk with hormone replacement therapy: an encore for estrogen?

PMID- 12513049
TI  - A rash decision.

PMID- 12513050
TI  - A complaint against "complaints".

PMID- 12513051
TI  - Alcohol and congestive heart failure.

PMID- 12513052
TI  - Alcohol and congestive heart failure.

PMID- 12513054
TI  - Risk for venous thromboembolism in carriers of the factor V Leiden mutation.

PMID- 12513056
TI  - Survival in Academy Award-winning actors and actresses.

PMID- 12513057
TI  - Survival in Academy Award-winning actors and actresses.

PMID- 12513058
TI  - Contamination of the blood supply in the 1980s and 1990s.

PMID- 12513059
TI  - J-shaped relationship in hypertension.

PMID- 12513061
TI  - Hematopoietic stem-cell transplantation for the Bernard-Soulier syndrome.

PMID- 12513063
TI  - Summaries for patients. Postmenopausal hormone therapy and blood sugar.

PMID- 12513064
TI  - Summaries for patients. Overweight and obesity by middle age are associated with
      shortened lifespan.

PMID- 12513065
TI  - Summaries for patients. Genes of the renin-angiotensin system and the development
      of obesity in men.

PMID- 12513066
TI  - Summaries for patients. Evaluation of risk factors for congestive heart failure.

PMID- 12513067
TI  - The STARD statement for reporting studies of diagnostic accuracy: explanation and
      elaboration.
AB  - The quality of reporting of studies of diagnostic accuracy is less than optimal.
      Complete and accurate reporting is necessary to enable readers to assess the
      potential for bias in the study and to evaluate the generalizability of the
      results. A group of scientists and editors has developed the STARD (Standards for
      Reporting of Diagnostic Accuracy) statement to improve the reporting the quality
      of reporting of studies of diagnostic accuracy. The statement consists of a
      checklist of 25 items and flow diagram that authors can use to ensure that all
      relevant information is present. This explanatory document aims to facilitate the
      use, understanding, and dissemination of the checklist. The document contains a
      clarification of the meaning, rationale, and optimal use of each item on the
      checklist, as well as a short summary of the available evidence on bias and
      applicability. The STARD statement, checklist, flowchart, and this explanation
      and elaboration document should be useful resources to improve reporting of
      diagnostic accuracy studies. Complete and informative reporting can only lead to
      better decisions in health care.

PMID- 12513068
TI  - Resident stress.

PMID- 12513069
TI  - Resident stress.

PMID- 12513070
TI  - Nitrite catalyzes reductive nitrosylation of the water-soluble Ferri-Heme model
      FeIII(TPPS) to FeII(TPPS)(NO).
AB  - Quantitative investigation of the reaction of the ferri-heme model compound
      Fe(III)(TPPS)(H(2)O)(2) (1) to give Fe(II)(TPPS)(NO) (2) (TPPS = tetra(4
      sulfonato-phenyl)porphinato) in buffered aqueous solution demonstrates a slow pH
      independent reductive nitrosylation pathway in the pH range 4-6. The rate of this
      reaction is subject to modest general base catalysis. In the course of this
      study, a surprising catalytic pathway whereby nitrite ion (NO(2)(-)) strongly
      catalyzes the reduction of 1 to 2 under reductive nitrosylation conditions was
      demonstrated.

PMID- 12513071
TI  - Creating new binding sites in ligands and metal complexes using the Negishi cross
      coupling reaction.
AB  - The Negishi cross-coupling reaction creates a new binding site in a ruthenium
      complex with high efficiency as exemplified by the synthesis of a
      heterodimetallic ruthenium-osmium complex.

PMID- 12513072
TI  - A novel nonlinear optical crystal for the IR region: noncentrosymmetrically
      crystalline CsCdBr3 and its properties.
AB  - A noncentrosymmetric crystal structure of CsCdBr(3) has been successfully
      observed with X-ray single-crystal structure analysis. It crystallizes in the
      hexagonal space group P6(3)mc, with a = 7.7281(14) A, b = 7.7281(14) A, c =
      6.742(2) A, alpha = 90 degrees, beta = 90 degrees, gamma = 120 degrees, Z = 2. It
      was obtained by a new preparation procedure different from that reported in the
      literature that gave a centrosymmetric structure. The structure contains Cd-Br
      octahedrons, which are connected in a plane-sharing way to form one-dimensional
      long chains. Each octahedron is slightly distorted, as the three Cd-Br bond
      lengths are 2.774 A, while the other three Cd-Br bond lengths are 2.804 A. The
      distortion directions of all of the octahedrons are almost parallel and give rise
      to the accumulation of the microcosmic nonlinear optical (NLO) coefficient. The
      Kurtz powder technique shows that CsCdBr(3) has a powder second harmonic
      generation of about 2 times as large as that of potassium dihydrogen phosphate
      (KDP). It shows excellent transparency in the visible and infrared regions. The
      thermal stability is also good. Therefore it may be utilized as a potential
      nonlinear optical crystal for the IR region.

PMID- 12513073
TI  - Synthesis and reactions of cubane-type iron-sulfur-phosphine clusters, including
      soluble clusters of nuclearities 8 and 16.
AB  - A family of soluble, reduced iron-sulfur clusters with nuclearities 4, 8, and 16
      having tertiary phosphine ligation and based on the Fe(4)S(4) cubane-type
      structural motif has been synthesized. The results of this investigation
      substantially extend and improve the results of our original work on iron-sulfur
      phosphine clusters (Goh, C.; Segal, B. M.; Huang, J.; Long, J. R.; Holm, R. H. J.
      Am. Chem. Soc. 1996, 118, 11844). A general property of this cluster family is
      facile phosphine substitution. The clusters [Fe(4)S(4)(PR(3))(4)](+) are
      precursors to monosubstituted [Fe(4)S(4)(PR(3))(3)X] (X = Cl-, RS-), homoleptic
      [Fe(4)S(4)(SR)(4)](3-), and all-ferrous monocubanes [Fe(4)S(4)(PR(3))(4)] (R =
      Pr(i), Cy, Bu(t); generated in solution). In turn,
      [Fe(4)S(4)(PPr(i)()(3))(3)(SSiPh(3))] and [Fe(4)S(4)(PPr(i)(3))(4)] can be
      transformed into the dicubanes [Fe(8)S(8)(PPr(i)()(3))(4)(SSiPh(3))(2)] and
      [Fe(8)S(8)(PPr(i)((3))(6)], respectively. Further, the tetracubanes
      [Fe(16)S(16)(PR(3))(8)] are also accessible from [Fe(4)S(4)(PR(3))(4)] under
      different conditions. X-ray structures are described for [Fe(4)S(4)(PCy(3))(3)X]
      (X = Cl-, PhS-), [Fe(8)S(8)(PPr(i)(3))(4)(SSiPh(3))(2)],
      [Fe(8)S(8)(PPr(i)()(3))(6)], and [Fe(16)S(16)(PCy(3))(8)]. The monosubstituted
      clusters show different distortions of the [Fe(4)S(4)](+) cores from idealized
      cubic symmetry. The dicubanes possess edge-bridged double cubane structures with
      an Fe(2)(mu(4)-S)(2) bridge rhomb and idealized C(2)(h)() symmetry. The ready
      cleavage of these clusters into single cubanes is considered a probable
      consequence of strained bond angles at the mu(4)-S atoms. Tetracubanes contain
      four individual cubanes, each of which is implicated in two bridge rhombs so as
      to generate a cyclic structure of idealized D(4) symmetry. Redox properties and
      Mossbauer spectroscopic parameters are reported. The species
      [Fe(4)S(4)(PR(3))(4)] (in solution), [Fe(8)S(8)(PR(3))(6)], and
      [Fe(16)S(16)(PR(3))(8)] are the only synthetic all-ferrous clusters with
      tetrahedral iron sites that have been isolated. Their utility as precursors to
      other highly reduced iron-sulfur clusters is under investigation.

PMID- 12513074
TI  - Correlations of synthetic, spectroscopic, structural, and speciation studies in
      the biologically relevant cobalt(II)-citrate system: the tale of the first
      aqueous dinuclear cobalt(II)-citrate complex.
AB  - Synthetic efforts targeting soluble species of Co(II) with the low molecular mass
      physiological ligand citric acid led to the isolation of the first dinuclear
      complex [Co(2)(C(6)H(5)O(7))(2)(H(2)O)(4)](2-), at pH approximately 5, in the
      form of its K+ (1) and Na+ (2) salts. Both 1 and 2 were characterized
      analytically, spectroscopically (FT-IR, UV/visible, EPR), and magnetically.
      Complex 1 crystallizes in the monoclinic space group P2(1)/n, with a = 10.348(5)
      A, b = 11.578(6) A, c = 12.138(6) A, beta = 112.62(2) degrees, V = 1342(1) A(3),
      and Z = 2. Complex 2 crystallizes in the monoclinic space group P2(1)/c, with a =
      9.234(4) A, b = 11.913(4) A, c = 11.728(6) A, beta = 99.93(2) degrees, V =
      1271(1) A(3), and Z = 2. X-ray crystallography on 1 and 2 reveals the presence of
      two Co(II) ions, in a dinuclear assembly, octahedrally coordinated by two citrate
      ligands in a tridentate fashion. The octahedral environment around each Co(II) is
      complemented by another singly bonded citrate belonging to the adjacent Co(II)
      unit and two water molecules. Magnetic susceptibility and EPR studies on 1, in
      the solid state, corroborate the X-ray results, indicating a weak interaction
      between the two Co(II) ions. Moreover, EPR and UV/visible studies in solution
      suggest that 1 does not retain its dimeric structure, yielding a mononuclear
      octahedral Co(II)-citrate species. Detailed speciation studies suggest the
      presence of a number of species including the mononuclear complex
      [Co(C(6)H(5)O(7))](-), optimally present around pH approximately 5. In consonance
      with EPR and UV/visible spectroscopy, [Co(C(6)H(5)O(7))](-) is likely the
      scaffolding unit on the basis of which the dimer
      [Co(2)(C(6)H(5)O(7))(2)(H(2)O)(4)](2-) is isolated from aqueous solutions.
      Collectively, this comprehensive study offers significant structural insight into
      the Co(II)-citrate speciation and the elucidation of the role of Co(II) in
      biological fluids.

PMID- 12513075
TI  - Intrinsic acid-base properties of purine derivatives in aqueous solution and
      comparison of the acidifying effects of platinum(II) coordinated to N1 or N7:
      acidifying effects are reciprocal and the proton "outruns" divalent metal ions.
AB  - The effect of Pt(2+) coordination, in particular of (dien)Pt(2+) or cis
      (NH(3))(2)Pt(2+), on the acid-base properties of the purine ligands 9
      ethylguanine (9EtG), 9-methylhypoxanthine (9MeHx), inosine (Ino), 9-methyladenine
      (9MeA), and N6',N6',N9-trimethyladenine (TriMeA) is quantitatively evaluated. The
      corresponding acidity constants of the complexes are calculated by curve-fitting
      procedures using previously published (1)H NMR shift data which had been measured
      in aqueous solution (D(2)O) in dependence on pH (pD). Comparison of the pK(a)
      values of the ligands with those of the Pt(2+) complexes reveals the expected
      behavior for the (N7)-platinated complexes; i.e., the (N1)H(0/+) sites are
      acidified due to charge repulsion. However, Pt(2+) coordination at (N1)(-)(/0)
      sites leads to an (already previously observed) apparent increase in the basicity
      of the N7 sites for the guanine, hypoxanthine, and adenine residues; this is also
      the case if Pt(2+) is bound to N3. Coordination of Pt(2+) to both the (N1)(-) and
      N7 sites of 9EtG results apparently in an enhanced basicity of N3 if compared
      with the release of the proton from the (N3)H(+) site in H(2)(9EtG)(2+). For the
      former cases in aqueous solution (H(2)O) it is now proven for a comprehensive set
      of data (seven examples), by taking into account the intrinsic basicities of the
      various N7 sites via micro acidity constants, that the acidifications are
      reciprocal and identical. This means Pt(2+) coordinated to (N1)(-)(/0) sites in
      guanine, hypoxanthine, or adenine residues acidifies the (N7)H(+) unit to the
      same extent as (N7)-coordinated Pt(2+) acidifies the (N1)H(0/+) site. In other
      words, the apparently increased basicity of N7 upon Pt(2+) coordination at (N1)(
      )(/0) sites disappears if the micro acidity constants of the appropriate
      isocharged tautomers of the ligand are properly taken into account. It is further
      proven, on the basis of the evaluations of the nucleotide analogue 9-[2
      (phosphonomethoxy)ethyl]adenine (PMEA), that these given conclusions are also
      valid for nucleotides. In addition, it is shown that the mentioned apparent
      basicity increase, which results from the use of macro acidity constants, has its
      origin in the fact that the proton-metal ion (Pt(2+)) interaction (the extent of
      which depends on the kind of metal ion involved) is less pronounced than the
      proton-proton interaction. Finally, the proven reciprocal behavior will now allow
      one to determine micro acidity constants of ligands by studying complexes formed
      with kinetically inert metal ions. A further result of interest is the proof that
      the competition of Pt(2+) (or Pd(2+)) with the proton for the (N1)(-) and N7
      binding sites of inosinate results in the isomer where the metal ion is at N7
      with the proton relegated to (N1)(-); this isomer is favored by a factor of about
      2000 compared with the one having the metal ion at (N1)(-) and the proton at N7.

PMID- 12513076
TI  - Fe(III) coordination properties of a new saccharide-based exocyclic
      trihydroxamate analogue of ferrichrome.
AB  - The coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl
      2,3,4-tris-O-[4-(N-hydroxy-N-methylcarbamoyl)-n-butyrate]-alpha-d-glucopyranoside
      (H(3)L), is reported, along with its pK(a) values, Fe(III) and Fe(II) chelation
      constants, and aqueous-solution speciation as determined by spectrophotometric
      and potentiometric titration techniques. The use of a saccharide platform to
      synthesize a hexadentate trihydroxamic acid chelator provides some advantages
      over other approaches to ferrichrome models, including significant water
      solubility and hydrogen-bonding capability of the backbone that can potentially
      provide favorable receptor recognition and biological activity. The pK(a) values
      for the hydroxamate moieties were found to be similar to those of other
      trihydroxamates. Proton-dependent Fe(III)-H(3)L and Fe(II)-H(3)L equilibrium
      constants were determined using a model involving the sequential protonation of
      the iron(III)- and iron(II)-ligand complexes. These results were used to
      calculate the formation constants, log beta(110) = 31.86 for Fe(III)L and 12.1
      for Fe(II)L(-). The calculated pFe value of 27.1 indicates that H(3)L possesses
      an Fe(III) affinity comparable to or greater than those of ferrichrome and other
      ferrichrome analogues and is thermodynamically capable of removing Fe(III) from
      transferrin. E(1/2) for the Fe(III)L/Fe(II)L(-) couple was determined to be -436
      mV from quasi-reversible cyclic voltammograms at pH = 9, and the pH-dependent
      E(1/2) profile was used to determine the Fe(II)L(-) protonation constants.

PMID- 12513077
TI  - Pendant cyclodicarbaphosphazatriene-containing monomers and polymers: synthesis,
      crystal structures and polymerization behavior of [NC(NMe2)]2[NP(O-C6H4-p-C6H4-p
      CH=CH2)(X)], X = Cl, OCH2CF3, OC6H5, OC6H4-m-CH3, OC6H4-p-Br.
AB  - The reaction of the dicarbaphosphazene, [NC(NMe(2))](2)[NPCl(2)] (2), with the
      sodium salt of 4-hydroxy-4'-vinylbiphenyl afforded the vinyl group containing
      monomer [NC(NMe(2))](2)[NP(Cl)(O-C(6)H(4)-p-C(6)H(4)-p-CH=CH(2))] (3).
      Replacement of the lone chlorine atom of 3 by oxygen nucleophiles gave
      [NC(NMe(2))](2)[NP(OR)(O-C(6)H(4)-p-C(6)H(4)-p-CH=CH(2))] [R = CH(2)CF(3) (4);
      C(6)H(5) (5); C(6)H(4)-m-CH(3) (6); C(6)H(4)-p-Br(7)]. The X-ray crystal
      structures of 3-7 reveal that all the cyclodicarbaphosphazenes have a planar
      N(3)PC(2) ring; the ring carbons are completely planar, while the geometry around
      phosphorus is pseudotetrahedral. The presence of weak intermolecular hydrogen
      bonding [C-H---X(Cl or Br), C-H---N, or C-H---pi] interactions in 3-7 leads to
      the formation of polymeric architectures in the solid-state. The monomers 4-7 can
      be polymerized by a free-radical initiator to afford the corresponding air-stable
      homopolymers 8-11. These have moderate molecular weights with polydispersity
      indices ranging from 1.33 to 1.58. All of these polymers have high glass
      transition temperatures and have excellent thermal stability.

PMID- 12513078
TI  - "True" inorganic heterocycles: structures and stability of group 13-15 analogues
      of benzene and their dimers.
AB  - Group 13-15 inorganic analogues of benzene, [HMYH](3) (M = B, Al, Ga; Y = N, P,
      As), mixed heterocycles of the type [BAlGaNPAs]H(6) and their dimers have been
      theoretically examined at the B3LYP/TZVP level of theory. Six different isomers
      have been structurally characterized for the mixed compounds [BAlGaNPAs]H(6). B-N
      bonding strongly (about approximately 90-100 kJ mol(-)(1)) stabilizes the mixed
      heterocycles, followed by the preference of the Al-N bonded structures over Ga-N
      bonded ( approximately 30-40 kJ mol(-1)), while B-P bonding is slightly (5-10 kJ
      mol(-1)) more favorable compared to B-As. Thus, the bonding pattern is predicted
      to be the most stable, followed by the core. Processes of [HMYH](3) formation
      from donor-acceptor complexes H(3)MYH(3) are predicted to be thermodynamically
      favorable for all MY combinations. Dimerization reactions of the coordinationally
      unsaturated [HMYH](3) heterocycles yielding hexamer clusters [HMYH](6) are found
      to be exothermic, with the exception of borazine, for which, as for benzene,
      dimerization is strongly endothermic due to the aromaticity of C(6)H(6) and
      [HBNH](3). Despite the high endothermicity of [HBNH](3) dimerization, the B-N
      bond formation is the driving force of the dimerization of mixed species
      [BAlGaNPAs]H(6). The dimerization enthalpies of [BAlGaNPAs]H(6) may be both exo-
      and endothermic, depending on the bonding pattern of the isomers. A complete set
      of mean MY bond energies in four- and six-membered cycles of [HMYH](6) was
      derived. The MY energies were found to be transferable quantities and may serve
      for a qualitative prediction of the relative stability of different isomers of
      mixed cluster compounds. [BAlGaNPAs](2)H(12) clusters are promising synthetic
      targets, they are expected to serve as single-source precursors for the
      stoichiometry-controlled CVD processes of the group 13-15 composites. A strategy
      of their synthesis and the most suitable starting systems have been also
      predicted.

PMID- 12513079
TI  - Deprotonation of zinc(II)-water and zinc(II)-alcohol and nucleophilicity of the
      resultant zinc(II) hydroxide and zinc(II) alkoxide in double-functionalized
      complexes: theoretical studies on models for hydrolytic zinc enzymes.
AB  - The factors governing the deprotonation ability of zinc(II)-water and zinc(II)
      alcohol and nucleophilicity of the resultant zinc(II) hydroxide and zinc(II)
      alkoxide as complex models for zinc enzymes have been investigated through
      Hartree-Fock and density-functional theory methods with the 6-311++G(d,p) basis
      set. Our calculations showed that in these double-functionalized complexes (i.e.,
      zinc complexes having both a zinc(II)-alcohol motif and a zinc(II)-water motif)
      zinc(II)-alcohol is preferred in deprotonation over zinc(II)-water (i.e.,
      zinc(II)-alcohol has a much lower pK(a) than zinc-coordinated water in the same
      molecule). Natural bond orbital analysis revealed that zinc(II) alkoxides are
      more nucleophilic than their respective counterparts zinc(II) hydroxides. The
      analysis of the transition state in the transformation reaction from zinc(II)
      hydroxide species to zinc(II) alkoxide species indicates that zinc(II) alkoxides
      are the preferred deprotonated species not only thermodynamically but also
      kinetically. Further examination of the proposed mechanisms of the zinc(II)
      alkoxide-promoted transesterification path and the zinc(II) hydroxide-promoted
      hydrolysis path revealed the structures of the intermediates and energy diagrams
      in the reactions. These results, entitled double-functionalized complexes, for
      the first time, put a firm theoretical foundation of why the zinc(II)-alcoholic
      OH is a better model for hydrolytic zinc enzymes (having both stronger acidity
      and better nucleophilicity).

PMID- 12513080
TI  - Kinetics and mechanisms of S(IV) reductions of bromite and chlorite ions.
AB  - The reaction of bromite with aqueous S(IV) is first order in both reactants and
      is general-acid catalyzed. The reaction half-lives vary from 5 ms (p[H+] 5.9) to
      210 s (p[H+] 13.1) for 0.7 mM excess S(IV) at 25 degrees C. The proposed
      mechanism includes a rapid reaction (k(1) = 3.0 x 10(7) M(-1) s(-1)) between
      BrO(2)(-) and SO(3)(2-) to form a steady-state intermediate, (O(2)BrSO(3))(3-).
      General acids assist the removal of an oxide ion from (O(2)BrSO(3))(3-) to form
      OBrSO(3)(-), which hydrolyzes rapidly to give OBr(-) and SO(4)(2-). Subsequent
      fast reactions between HOBr/OBr(-) and SO(3)(2-) give Br(-) and SO(4)(2-) as
      final products. In contrast, the chlorite reactions with S(IV) are 5-6 orders of
      magnitude slower. These reactions are specific-acid, not general-acid, catalyzed.
      In the proposed mechanism, ClO(2)(-) and SO(3)H(-)/SO(2) react to form
      (OClOSO(3)H)(2)(-) and (OClOSO(2))(-) intermediates which decompose to form OCl(
      ) and SO(4)(2-). Subsequent fast reactions between HOCl/OCl(-) and S(IV) give Cl-
      and SO(4)(2-) as final products. SO(2) is 6 orders of magnitude more reactive
      than SO(3)H-, where k(5)(SO(2)/ClO(2)(-)) = 6.26 x 10(6) M(-1) s(-1) and
      k(6)(SO(3)H(-)/ClO(2)(-)) = 5.5 M(-1) s(-1). Direct reaction between ClO(2)(-)
      and SO(3)(2-) is not observed. The presence or absence of general-acid catalysis
      leads to the proposal of different connectivities for the initial reactive
      intermediates, where a Br-S bond forms with BrO(2)(-) and SO(3)(2-), while an O-S
      bond forms with ClO(2)(-) and SO(3)H-.

PMID- 12513081
TI  - Synthesis, separation, and assignment of the seven geometric isomers of
      [Co(dien)(ibn)Cl]2+.
AB  - All seven possible geometric isomers (four mer and three facial) for the
      [Co(dien)(ibn)Cl](2+) system have been synthesized (dien = diethylenetriamine,
      ibn = 1,2-diamino-2-methylpropane). Their structures in dimethyl sulfoxide
      solution have been uniquely determined by two-dimensional NMR spectroscopy
      (DQCOSY and NOESY).

PMID- 12513082
TI  - Arene-ruthenium complexes of an acyclic thiolate-thioether and tridentate
      thioether derivatives resulting from ring-closure reactions.
AB  - The reaction of [(eta(6)-arene)RuCl(2)](2) (arene = C(6)Me(6), 1,4
      MeC(6)H(4)CHMe(2)) with a large excess of the dianion of bis(2-mercaptoethyl)
      sulfide, (HSCH(2)CH(2))(2)S, obtained from deprotonation of the dithiol with
      freshly prepared NaOMe, gives the deep red, monomeric complexes [(eta(6)
      arene)Ru(eta(3)-C(4)H(8)S(3))] (arene = C(6)Me(6) (5), 1,4-MeC(6)H(4)CHMe(2) (6))
      in which the dianion is bound to the metal atom through one thioether and two
      thiolate sulfur atoms. Complex 5 reacts with [(eta(6)-C(6)Me(6))RuCl(2)](2) (4)
      in a 2:1 mole ratio to give a quantitative yield of the chloride salt of a
      binuclear cation [((eta(6)-C(6)Me(6))Ru)(2)Cl(mu(2)-eta(2):eta(3)
      C(4)H(8)S(3))](+) (7) in which the thiolate sulfur atoms of the [(eta(6)
      C(6)Me(6))Ru(eta(3)-C(4)H(8)S(3))] group bridge to a (eta(6)-C(6)Me(6))RuCl unit.
      This compound is also obtained directly from the reaction of 4 with the
      dithiolate, if the Ru dimer is used in large excess. The binuclear complex
      [((eta(6)-C(6)Me(6))Ru)(2)(MeCN)(mu(2)-eta(2):eta(3)
      C(4)H(8)S(3))](PF(6))(2).MeCN, (9)(PF(6))(2).MeCN, is obtained by treatment of
      (7)Cl with NH(4)PF(6) in acetonitrile. Protonation of 5 with HCl gave the mono-
      and diprotonated derivatives viz. [(eta(6)-C(6)Me(6))Ru(eta(3)-C(4)H(9)S(3))]Cl,
      (8)Cl, and [(eta(6)-C(6)Me(6))Ru(eta(3)-C(4)H(10)S(3))]Cl(2), (10)Cl(2),
      respectively. The reaction of 5 with methyl iodide gives both the mono- and di-S
      methylated derivatives. Treatment of 5 with dibromoalkanes, Br(CH(2))(n)Br (n = 1
      5), effects ring closure to give the (eta(6)-C(6)Me(6))Ru dications containing
      the trithia mesocyclic zS3 (z = 8-12) ligands, isolated as their PF(6) salts. The
      X-ray crystal structures of 5, 6, the solvates of (7)Cl and (9)(PF(6))(2), and
      the trithia mesocyclic Ru complexes (eta(6)-C(6)Me(6))Ru(zS3)(PF(6))(2) (z = 8
      11) are reported.

PMID- 12513083
TI  - Benzene thermal conversion to nanocrystalline indium nitride from sulfide at low
      temperature.
AB  - A benzene thermal conversion route has been successfully developed to prepare
      nanocrystalline indium nitride at 180-200 degrees C by choosing NaNH(2) and
      In(2)S(3) as novel nitrogen and indium sources. This route has been also extended
      to the synthesis of other group III nitrides. The product InN was characterized
      by X-ray diffraction (XRD), transmission electron microscopy (TEM) and high
      resolution TEM, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and
      infrared spectroscopy (IR). The optical properties of nanocrystalline InN were
      also recorded by means of UV-vis absorption spectroscopy and photoluminescence
      (PL) spectroscopy, indicating that the as-prepared sample was within the quantum
      confinement regime. Finally, the formation mechanism was also investigated.

PMID- 12513084
TI  - Synthesis and spectroscopic characterization of silver(I) complexes with the
      bis(1,2,4-triazol-1-yl)alkane ligand tz2(CH2). X-ray structures of two- and three
      dimensional coordination polymers.
AB  - 1:1 AgX:tz(2)(CH(2)) (X = NO(3), NO(2), ClO(4)), 3:4 (X = O(3)SCF(3) (=OTf),
      O(2)CCF(3) (= tfa)), and 2:1 adducts (X = BrO(3)) have been synthesized and
      characterized in the solid state and in solution by analyses, spectral (IR, far
      IR, (1)H and (13)C NMR, ESI MS) data, and conductivity measurements. The crystal
      structures of the 1:1 AgNO(3):tz(2)(CH(2)) and AgNO(2):tz(2)(CH(2)) adducts
      determined by X-ray studies show that tz(2)(CH(2)) coordinates to silver through
      the exodentate nitrogen atoms at the 4-positions of the triazole rings, yielding
      neutral polymers, while the ionic Ag(OTf):tz(2)(CH(2)) (3:4) adduct has a three
      dimensional polymeric cation. The NMR and ESI MS data suggest that tz(2)(CH(2))
      is only weakly coordinating, adducts between Ag(I) and CH(3)CN being more
      prevalent in acetonitrile solution.

PMID- 12513085
TI  - Bond valence sums in coordination chemistry. The calculation of the oxidation
      state of cerium in complexes containing cerium bonded only to oxygen.
AB  - A total of 119 CeO(n)fragments with n = 3-12 were analyzed by using the bond
      valence sum, or BVS, method to yield new R(0) values for Ce(III)-O of 2.121(13) A
      and for Ce(IV)-O of 2.068(12) A. These R(0) values can be used to calculate the
      oxidation state of Ce in complexes where Ce is bonded only to O ligands.
      Furthermore, the average R(0) value of 2.094 A gives a good indication of whether
      the oxidation state of the Ce ion is +3 or +4 from the observed distances without
      any assumptions. The fact that complexes with coordination numbers of 10-12 are
      in agreement is significant since this study is the first example which indicates
      that high coordination numbers also follow BVS rules. The Ce-O distances used in
      deriving the R(0) values for the +3 and +4 complexes are tabulated as a function
      of coordination number and have a wide range of values, but the average Ce-O
      distance reflects the requirement that the BVS must equal the oxidation state.
      Several examples are given where the oxidation state of the Ce ion is apparently
      incorrectly assigned, as well as cases where problems with the X-ray structure
      determinations are indicated by a disagreement between the postulated and
      calculated oxidation state.

PMID- 12513086
TI  - Syntheses and structures of isoindoline complexes of Zn(II) and Cu(II): an
      unexpected trinuclear Zn(II) complex.
AB  - Deprotonation of the tridentate isoindoline ligand 1,3-bis[2-(4
      methylpyridyl)imino]-isoindoline, 4'-MeLH, and reaction with hydrated zinc(II)
      perchlorate produces an unexpected trinuclear Zn(II) complex, [Zn(3)(4'
      MeL)(4)](ClO(4))(2).5H(2)O (1), whereas reaction with hydrated copper(II)
      perchlorate in methanol produces the expected mononuclear product, [Cu(4'
      MeL)(H(2)O)(2)]ClO(4) (2). X-ray diffraction shows that the trinuclear Zn(II)
      complex (1) contains a linear zinc backbone, and the arrangement of ligands about
      the outer chiral zinc(II) atoms is helical. The two terminal zinc ions exhibit
      approximate C(2) site symmetry, with tetrahedral coordination by two pyrrole and
      two pyridyl nitrogen atoms of the potentially tridentate isoindoline ligands. The
      central zinc ion exhibits approximate tetrahedral symmetry, with coordination by
      four pyridyl nitrogen atoms of four different isoindoline ligands. Pyridyl
      pyrrole intramolecular pi-stacking interactions contribute to the stability of
      the trinuclear cation. The structure of the mononuclear copper(II) complex cation
      in 2 is best described as a distorted trigonal bipyramid. The isoindoline anion
      binds Cu(II) in both axial positions and one of the equatorial positions; water
      molecules occupy the other two equatorial positions.

PMID- 12513087
TI  - Self-assembled supramolecular M9 (Mn(II), Fe(III), Zn(II)), M5 (Fe(III)), and
      [M3]2 (Pb(II)) complexes: structural, magnetic, and Mossbauer properties.
AB  - The tritopic ligand 2poap self-assembles in the presence of Zn(NO(3))(2) and
      Fe(NO(3))(3) to form homoleptic [3 x 3] nonanuclear M(9) (M = Zn(II), Fe(III))
      square grid structures and with Pb(ClO(4))(2) to form a dimerized linear
      trinuclear [Pb(3)](2) structure. Cl2poap and Cl2poapz form self-assembled
      homoleptic [3 x 3] Mn(II)(9) square grids with Mn(ClO(4))(2) and Mn(NO(3))(2),
      respectively, but an unusual incompletely metalated Fe(III)(5) square grid is
      formed on reaction of Cl2poap with Fe(ClO(4))(3). X-ray structures are reported
      for [Mn(9)(Cl2poap-2H)(6)](ClO(4))(6).10H(2)O (3), [Mn(9)(Cl2poapz-2H)(6)]
      (NO(3))(6).22H(2)O (4), [Zn(9)(2poap-2H)(3)(2poap-H)(3)](NO(3))(9).24H(2)O (5),
      [Pb(3)(2poap-2H) (ClO(4))(4)](2).8H(2)O (6), and [Fe(5)(Cl2poap
      H)(6)](ClO(4))(9).34.5H(2)O (7). Compound 3 crystallized in the monoclinic
      system, space group P(-)1, with a = 18.179(1) A, b = 18.857(1) A, c = 25.871(2)
      A, alpha = 70.506(2) degrees, beta = 86.440(1) degrees, gamma = 75.175(2)
      degrees, and z = 2. Compound 4 crystallized in the monoclinic system, space group
      P(-)1, with a = 16.900(2) A, b = 20.02393) A, c = 25.663() A, alpha = 84.743(3)
      degrees, beta = 84.885(2) degrees, gamma = 67.081(2) degrees, and z = 2. Compound
      5 crystallized in the monoclinic system, space group P(-)1, with a = 18.482(1) A,
      b = 18.774(1) A, c = 28.112(2) A, alpha = 104.020(1) degrees, beta = 97.791(1)
      degrees, gamma = 117.036(1) degrees, and z = 2. Compound 6 crystallized in the
      monoclinic system, space group P(-)1, with a = 10.0513(6) A, b = 11.0958(6) A, c
      = 17.334(1) A, alpha = 100.932(1) degrees, beta = 100.387(1) degrees, gamma =
      94.565(1) degrees, and z = 2. Compound 7 crystallized in the monoclinic system,
      space group P(-)1, with a = 19.164(1) A, b = 19.587(2) A, c = 26.673(2) A, alpha
      = 76.430(2) degrees, beta = 78.834(2) degrees, gamma = 64.973(1) degrees, and z =
      2. Compound 3 exhibits intramolecular antiferromagnetic exchange within the
      nonanuclear [Mn(9)(mu-O)(12)] grid structure (J = -4.6 cm(-1)), while the
      analogous nonanuclear complex [Fe(9)(2poap-2H)(6)](NO(3))(15).18H(2)O (8) is
      dominated by intramolecular antiferromagnetic coupling at high temperatures but
      exhibits a low-temperature feature indicative of additional ferromagnetic
      interactions. The isolated pentanuclear Fe(5) [4 + 1] square grid in 7, with
      distant Fe-Fe bridging, exhibits very weak antiferromagnetic coupling (J = -0.2
      cm(-1)). Mossbauer spectroscopy data are consistent with high-spin Fe(III)(9) and
      Fe(III)(5) structures.

PMID- 12513088
TI  - Light-induced metastable linkage isomers of ruthenium sulfur dioxide complexes.
AB  - The irradiation of ruthenium-sulfur dioxide complexes of general formula trans
      [Ru(II)(NH(3))(4)(SO(2))X]Y with laser light at low temperature results in
      linkage isomerization of SO(2), starting with eta(1)-planar S-bound to eta(2)
      side S,O-bound SO(2). The solid-state photoreaction proceeds with retention of
      sample crystallinity. Following work on trans-[Ru(NH(3))(4)Cl(eta(1)-SO(2))]Cl
      and trans-[Ru(NH(3))(4)(H(2)O)(eta(1)-SO2)](C(6)H(5)SO(3))(2) (Kovalevsky, A. Y.;
      Bagley, K. A.; Coppens, P. J. Am. Chem. Soc. 2002, 124, 9241-9248), we describe
      photocrystallographic, IR, DSC, and theoretical studies of trans
      [Ru(II)(NH(3))(4)(SO(2))X]Y complexes with (X = Cl(-), H(2)O, or CF(3)COO(-)
      (TFA(-))) and a number of different counterions (Y = Cl(-), C(6)H(5)SO(3)(-),
      Tos(-), or TFA(-)). Low temperature IR experiments indicate the frequency of the
      asymmetric and symmetric stretching vibrations of the Ru-coordinated SO(2) to be
      downshifted by about 100 and 165 cm(-1), respectively. Variation of the trans-to
      SO(2) ligand and the counterion increases the MS2 decay temperature from 230 K
      (trans-[Ru(II)(NH(3))(4)(SO(2))Cl]Cl) to 276 K (trans
      [Ru(II)(NH(3))(4)(SO(2))(H(2)O)](Tos)(2)). The stability of the MS2 state
      correlates with increasing sigma-donating ability of the trans ligand and the
      size of the counterion. Quantum chemical DFT calculations indicate the existence
      of a third eta(1)-O-bound (MS1) isomer, the two metastable states being 0.1-0.6
      eV above the energy of the ground-state complex.

PMID- 12513089
TI  - Structural variations across the lanthanide series of macrocyclic DOTA complexes:
      insights into the design of contrast agents for magnetic resonance imaging.
AB  - It was early shown that the macrocyclic Ln(DOTA) complexes (DOTA = 1,4,7,10-tetra
      azacyclododecane-N,N',N' ',N' "-tetraacetic acid) exists in solution as a mixture
      of two enantiomeric pairs of diastereoisomers differing in the ligand
      conformation, namely, square antiprismatic (SA) and twisted square antiprismatic
      (TSA) geometries, respectively. Later, extensive (1)H NMR investigations
      suggested that a coordination change may be superimposed on this conformational
      equilibrium involving two additional structures in which the metal ion possesses
      a coordination number of eight (CN 8). It was predicted that these two species,
      lacking the apical coordinated water molecule, would maintain the SA and TSA
      coordination geometries, and therefore, they have been labeled as SA' and TSA',
      respectively. In this work we report the X-ray solid-state crystal structure
      determination of six Ln(DOTA) complexes representative of all four coordination
      geometry typologies deduced from NMR solution studies. A distinctive structural
      feature that discriminates SA (and SA') and TSA (and TSA') structures is
      represented by the twist angle between the two square planes of the antiprism,
      the basal four nitrogen, and the apical four oxygen planes. [Ce(DOTA)(H(2)O)](-)
      displays a TSA structural typology with a twist angle of 25 degrees and a Ce
      O(water) distance of 2.59 A. The SA-type structure has been found in the case of
      complexes with Pr(III), Nd(III), and Dy(III), where the twist angle is 39, 39,
      and 38 degrees, respectively, and the metal-water oxygen distance varies
      significantly (Pr-O(w) 2.529 A; Nd-O(w) 2.508 A; and Dy-O(w) 2.474 A).
      [Tm(DOTA)](-) displays a TSA'-type structure with a twist angle of 24 degrees. As
      compared with the TSA structure of the corresponding Ce(III) complex, the Tm(III)
      complex shows an overall marked shrinkage of all metal-nitrogen and metal-oxygen
      distances (ca. 0.2 A), which reflects the contraction of the metal ionic radius
      across the series but also the effect associated with the decrease of the CN from
      9 to 8. In [Sc(DOTA)](-), the even smaller ionic radius of Sc(III) shifts the
      geometry of the coordination cage to the more compact SA' typology with a twist
      angle of 41 degrees, a value very similar to that found in the SA structures of
      lanthanide(III) ions with CN 9. Finally, an investigation was made into the
      hydration spheres of the complexes with SA and TSA geometries to account for the
      experimental evidence of a markedly different rate of water exchange for the two
      isomeric structures. This is of fundamental importance to the understanding of
      the corresponding Gd(III) complexes as MRI contrast agents.

PMID- 12513090
TI  - Novel one-dimensional tubelike and two-dimensional polycatenated metal-organic
      frameworks.
AB  - Two novel metal-organic frameworks (MOFs) [Zn(TITMB)(OAc)](OH).8.5H(2)O (1) and
      [Ag(TITMB)N(3)].H(2)O (2) [TITMB = 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6
      trimethylbenzene, OAc = acetate anion] were synthesized and their structures were
      determined by X-ray crystallography. Complex 1 crystallizes in tetragonal space
      group P(-)4 with a = 23.2664(7) and c = 11.9890(3) A and Z = 8. 1 has a one
      dimensional tubelike structure with large inner pore size of approximately 17 A.
      Complex 2 crystallizes in monoclinic space group C2 with a = 20.7193(10), b =
      11.5677(8), and c = 12.2944(6) A, beta = 125.5770(10) degrees, and Z = 4. 2
      consists of two-dimensional honeycomb networks that interpenetrate each other to
      generate a polycatenated structure. In these two complexes, both zinc(II) and
      silver(I) atoms are four-coordinated with the same tetrahedral coordination
      geometry. The topologies of 1 and 2 are predominated by the conformations of
      TITMB, which are cis, trans, trans in 1 and cis, cis, cis in 2, respectively.

PMID- 12513091
TI  - Formation of racemate and mesocate complexes from an achiral tripodal ligand
      containing three benzimidazole groups.
AB  - Two complexes of the achiral tripodal ligand tris(1-benzimidazolylethyl)amine
      (nteb), viz., [Mn(nteb)(2)(H(2)O)(2)](ClO(4))(2).CH(3)OH, 1, and
      [Ag(2)(nteb)(2)](CF(3)CO(2))(2).2H(2)O, 2, have been synthesized and
      characterized by IR, (1)H NMR, and EPR spectroscopy (1), electrospray mass
      spectrometry, thermogravimetric analysis, and X-ray crystallography. Compound 1
      contains chiral complex cations due to the same handedness of two nteb ligands
      (deltadelta or lambdalambda) but crystallizes as a racemate, while 2 contains a
      dinuclear mesocate because of the opposite handedness (deltalambda) of two nteb
      ligands. Crystal data for 1: space group P(-)1 with a = 9.471(4) A, b = 16.884(7)
      A, c = 19.906(8) A, alpha = 77.930(7) degrees, beta = 88.063(7) degrees, gamma =
      89.706(7) degrees, V = 3111(2) A(3), and Z = 2. Crystal data for 2: space group
      P(-)1 with a = 9.3390(12) A, b = 10.2168(13) A, c = 16.382(2) A, alpha =
      75.721(3) degrees, beta = 87.857(3) degrees, gamma = 71.738(3) degrees, V =
      1437.2(3) A(3), and Z = 1. In 1, water serves as an auxiliary ligand, connected
      to one imidazole N atom of each nteb ligand through a H-bridge; the cationic
      complexes are associated intermolecularly via pi.pi interactions. In contrast to
      1, the coordination to the Ag(+) ions in 2 occurs in a heterochiral manner and
      produces a dinuclear mesocate.

PMID- 12513092
TI  - Syntheses, crystal structures, and luminescent properties of lanthanide complexes
      with tripodal ligands bearing benzimidazole and pyridine groups.
AB  - Two tripodal ligands, bis(2-benzimidazolylmethyl)(2-pyridylmethyl)amine (L(1))
      and bis(2-pyridylmethyl)(2-benzimidazolylmethyl)amine (L(2)), were synthesized.
      With the third chromophoric ligand antipyrine (Antipy), three series of
      lanthanide(III) complexes were prepared: [LnL(1)(Antipy)(3)](ClO(4))(3) (series
      A), [LnL(1)(Antipy)Cl(H(2)O)(2)]Cl(2)(H(2)O)(2) (series B), and
      [LnL(2)(NO(3))(3)] (series C). The nitrate salt of the free ligand
      H(2)L(1).(NO(3))(2) and six complexes were structurally characterized: Pr(3+)A,
      Y(3+)A, Eu(3+)B, Eu(3+)C, Gd(3+)C and Tb(3+)C, in which the two A and three C
      complexes are isomorphous. Crystallographic studies showed that tripodal ligands
      L(1) and L(2) exhibited a tripodal coordination mode and formed 1:1 complexes
      with all lanthanide metal ions. The coordination numbers of the lanthanide metal
      ions for the A, B, and C complexes were 7, 8, and 10, respectively. Conductivity
      studies on the B and C complexes in methanol showed that, in the former, the
      coordinated Cl(-) dissociated to give 3:1 electrolytes and, in the latter, two
      coordinated NO(3)(-) ions dissociated to give 2:1 electrolytes. Detailed
      photophysical studies have been performed on the free ligands and their Gd(III),
      Eu(III), and Tb(III) complexes in several solvents. The results show a wide range
      in the emission properties of the complexes, which could be rationalized in terms
      of the coordination situation, the (3)LC level of the complexes, and the subtle
      variations in the steric properties of the ligands. In particular the Eu(3+)A and
      Tb(3+)A complexes, in which the central metal ions were wholly coordinated by
      chromophoric ligands of one L(1) and three antipyrine molecules, had relatively
      higher emission quantum yields than their corresponding B and C complexes.

PMID- 12513093
TI  - Synthesis, structure, and magnetic properties of [MnIII(salpn)NCS]n, a helical
      polymer, and the dimer [MnIII(salpn)NCS]2. Weak ferromagnetism in
      [MnIII(salpn)NCS]n related to the strong magnetic anisotropy in Jahn-Teller MnIII
      (salpnH2 = N,N'-bis(salicylidene)-1,3-diaminopropane).
AB  - Dimeric [Mn(salpn)NCS](2)(1) and polymeric [Mn(salpn)NCS](n)(2) are formed by the
      reaction of Mn(CH(3)CO(2))(2).4H(2)O, the schiff base, and thiocyanate. The
      formation of the two polymorphic forms is solvent and temperature dependent. 1:
      orthorhombic, space group Pbca, with a = 12.573(2) A, b = 13.970(7) A, c =
      18.891(9) A, and Z = 8. 2: orthorhombic, space group Pna2(1), with a =
      12.5277(14) A, b = 11.576(2) A, c = 11.513(2) A, and Z = 4. The dimers in 1 are
      held together by weak noncovalent S...pi (phenyl) interactions leading to a chain
      along the a-axis. Each monomeric unit of the polymer in 2 is related to its
      adjacent ones by a 2-fold screw axis leading to a helix along the c-axis. The
      exchange coupling is nondetectable in the dimer. The magnetic susceptibility of
      the helical chain fits a classical chain law with J = -3.2 cm(-1) and shows a
      weak ferromagnetic ordering below 7 K due to spin canting effects.

PMID- 12513094
TI  - Trans --> cis isomerization of trans-[(dppm)2Ru(H)(L)][BF4] (L = P(OR)3)
      complexes: preparation of cis-[(dppm)2Ru(eta2-H2)(L)][BF4]2.
AB  - A series of new dicationic dihydrogen complexes of ruthenium of the type cis
      [(dppm)(2)Ru(eta(2)-H(2))(L)][BF(4)](2) (dppm = Ph(2)PCH(2)PPh(2); L = P(OMe)(3),
      P(OEt)(3), PF(O(i)Pr)(2)) have been prepared by protonating the precursor hydride
      complexes cis-[(dppm)(2)Ru(H)(L)][BF(4)] (L = P(OMe)(3), P(OEt)(3), P(O(i)Pr)(3))
      using HBF(4).Et(2)O. The cis-[(dppm)(2)Ru(H)(L)][BF(4)] complexes were obtained
      from the trans hydrides via an isomerization reaction that is acid-accelerated.
      This isomerization reaction gives mixtures of cis and trans hydride complexes,
      the ratios of which depend on the cone angles of the phosphite ligands: the
      greater the cone angle, the greater is the amount of the cis isomer. The eta(2)
      H(2) ligand in the dihydrogen complexes is labile, and the loss of H(2) was found
      to be reversible. The protonation reactions of the starting hydrides with trans
      PMe(3) or PMe(2)Ph yield mixtures of the cis and the trans hydride complexes;
      further addition of the acid, however, give trans-[(dppm)(2)Ru(BF(4))Cl]. The
      roles of the bite angles of the dppm ligand as well as the steric and the
      electronic properties of the monodentate phosphorus ligands in this series of
      complexes are discussed. X-ray crystal structures of trans
      [(dppm)(2)Ru(H)(P(OMe)(3))][BF(4)], cis-[(dppm)(2)Ru(H)(P(OMe)(3))][BF(4)], and
      cis-[(dppm)(2)Ru(H)(P(O(i)Pr)(3))][BF(4)] complexes have been determined.

PMID- 12513095
TI  - Ruthenium complexes of 2-[(4-(arylamino)phenyl)azo]pyridine formed via
      regioselective phenyl ring amination of coordinated 2-(phenylazo)pyridine:
      isolation of products, X-ray structure, and redox and optical properties.
AB  - Aromatic ring amination reactions in the ruthenium complex of 2
      (phenylazo)pyridine is described. The substitutionally inert cationic brown
      complex [Ru(pap)(3)](ClO(4))(2) (1) (pap = 2-(phenylazo)pyridine) reacts smoothly
      with aromatic amines neat and in the presence of air to produce cationic and
      intense blue complexes [Ru(HL(2))(3)](ClO(4))(2) (2) (HL(2) = 2-[(4
      (arylamino)phenyl)azo]pyridine). These were purified on a preparative TLC plate.
      The X-ray structure of the new and representative complex 2c has been solved to
      characterize them. The results are compared with those of the starting complex,
      [Ru(pap)(3)](ClO(4))(2) (1). The transformation 1 --> 2 involves aromatic ring
      amination at the para carbon (with respect to the diazo function) of the pendant
      phenyl rings of all three coordinated pap ligands in 1. The transformation is
      stereoretentive, and the amination reaction is regioselective. The extended
      ligand HL(2) coordinates as a bidentate ligand and chelates to ruthenium(II)
      through the pyridine and one of the azo nitrogens. The amine nitrogen of this
      bears a hydrogen atom and remains uncoordinated. Similarly, the amination
      reaction on the mixed-ligand complex [Ru(pap)(bpy)(2)](ClO(4))(2) produces the
      blue complex [Ru(HL(2))(bpy)(2)](ClO(4))(2) (3) as anticipated. The reactions of
      [RuCl(2)(dmso)(4)] and [Ru(S)(2)(L)(2)](2+) (dmso = dimethyl sulfoxide, S =
      labile coordinated solvent, L = 2,2'-bipyridine (bpy) and pap) with the preformed
      HL(2) ligand have been explored. The structure of the representative complex
      [RuCl(2)(HL(2a))(2)] (5a) is reported. It has the chlorides in trans
      configuration while the pyridine as well as azo nitrogens are in cis geometry.
      Optical spectra and redox properties of the newly synthesized complexes are
      reported. All the ruthenium complexes of HL(2) are characterized by their intense
      blue solution colors. The lowest energy transitions in these complexes appear
      near 600 nm, which have been attributed to intraligand charge-transfer
      transitions. For example, the lowest energy visible range transition in
      [Ru(HL(2b))(3)](2+) appears at 602 nm and its intensity is 65 510 M(-1) cm(-1).
      All the tris chelates show multiple-step electron-transfer processes. In
      [Ru(HL(2))(3)](2+), six reductions waves constitute the complete electron
      transfer series. The electrons are believed to be added successively to the three
      azo functions. In the mixed-ligand chelates [Ru(HL(2))(pap)(2)](2+) and
      [Ru(HL(2))(bpy)(2)](2+) the reductions due to HL(2), pap, and bpy are observed.

PMID- 12513096
TI  - Syntheses, structures, and characterization of new lead(II)-tellurium(IV)-oxide
      halides: Pb3Te2O6X2 and Pb3TeO4X2 (X = Cl or Br).
AB  - The syntheses, structures, and characterization of four new lead(II)
      tellurium(IV)-oxide halides, Pb(3)Te(2)O(6)X(2) and Pb(3)TeO(4)X(2) (X = Cl or
      Br) are reported. The materials are synthesized by solid-state techniques, using
      Pb(3)O(2)Cl(2) or Pb(3)O(2)Br(2) and TeO(2) as reagents. The compounds have three
      dimensional structural topologies consisting of lead-oxide halide polyhedra
      connected to tellurium oxide groups. In addition, the Pb(2+) and Te(4+) cations
      are in asymmetric coordination environments attributable to their stereoactive
      lone pair. We also demonstrate that Pb(3)Te(2)O(6)X(2) and Pb(2)TeO(4)X(2) can be
      interconverted reversibly through the loss or addition of TeO(2). X-ray data:
      Pb(3)Te(2)O(6)Cl(2), monoclinic, space group C2/m (No. 12), a = 16.4417(11) A, b
      = 5.6295(4) A, c = 10.8894(7) A, beta = 103.0130(10) degrees, Z = 4;
      Pb(3)Te(2)O(6)Br(2), monoclinic, space group C2/m (No. 12), a = 16.8911(8) A, b =
      5.6804(2) A, c = 11.0418(5) A, beta = 104.253(2) degrees, Z = 4;
      Pb(3)TeO(4)Cl(2), orthorhombic, space group Bmmb (No. 63), a = 5.576(1) A, b =
      5.559(1) A, c = 12.4929(6) A, Z = 4; Pb(3)TeO(4)Br(2), orthorhombic, space group
      Bmmb (No. 63), a = 5.6434(4) A, b = 5.6434(5) A, c = 12.9172(6) A, Z = 4.

PMID- 12513097
TI  - Synthesis and coordination chemistry of the first C2-chiral bisoxazine ligand.
AB  - The ligand 2,5-bis(oxazinyl)-3,4-diethylpyrrole (4) was obtained in three
      reaction steps from the known pyrrole derivative 3,4-diethylpyrrole-2,5
      dicarboxylic acid (1) which was first coupled with 2 molar equiv of (S)-1-benzoxy
      3-butylamine to give the corresponding diamide 2 using dicyclohexylcarbodiimide
      and 1-hydroxybenzitriazole as coupling reagents. Subsequent hydrogenolysis of the
      benzyl ether functions yielded the dialcohol 3 which was cyclized in high yield
      after methylsulfonation and treatment with an excess of NaOH giving the target
      compound 2,5-bis[2-((S)-5-methyloxazinyl)]-3,4-diethylpyrrole (4). Lithiation of
      4 by reaction with 1 molar equivalent of nBuLi at -78 degrees C and addition of
      [PdCl(2)(COD)] to the lithium pyrrolide cleanly gave the palladium complex 5
      which was fully characterized. Complex 5 is unstable in solution and dimerizes to
      give a mixture of two diastereomeric helical dinuclear complexes, 6a and 6b,
      which cocrystallized in a 1:1 ratio to give X-ray quality single crystals. Both
      isomers possess virtual molecular 2-fold symmetry (though no crystallographic
      rotational symmetry), the molecular C(2)-axis being orthogonal to the Pd...Pd
      vector.

PMID- 12513098
TI  - [Ni(Et2PCH2NMeCH2PEt2)2]2+ as a functional model for hydrogenases.
AB  - The reaction of Et(2)PCH(2)N(Me)CH(2)PEt(2) (PNP) with [Ni(CH(3)CN)(6)](BF(4))(2)
      results in the formation of [Ni(PNP)(2)](BF(4))(2), which possesses both hydride-
      and proton-acceptor sites. This complex is an electrocatalyst for the oxidation
      of hydrogen to protons, and stoichiometric reaction with hydrogen forms
      [HNi(PNP)(PNHP)](BF(4))(2), in which a hydride ligand is bound to Ni and a proton
      is bound to a pendant N atom of one PNP ligand. The free energy associated with
      this reaction has been calculated to be -5 kcal/mol using a thermodynamic cycle.
      The hydride ligand and the NH proton undergo rapid intramolecular exchange with
      each other and intermolecular exchange with protons in solution.
      [HNi(PNP)(PNHP)](BF(4))(2) undergoes reversible deprotonation to form
      [HNi(PNP)(2)](BF(4)) in acetonitrile solutions (pK(a) = 10.6). A convenient
      synthetic route to the PF(6)(-) salt of this hydride involves the reaction of PNP
      with Ni(COD)(2) to form Ni(PNP)(2), followed by protonation with NH(4)PF(6). A
      pK(a) of value of 22.2 was measured for this hydride. This value, together with
      the half-wave potentials of [Ni(PNP)(2)](BF(4))(2), was used to calculate
      homolytic and heterolytic Ni-H bond dissociation free energies of 55 and 66
      kcal/mol, respectively, for [HNi(PNP)(2)](PF(6)). Oxidation of
      [HNi(PNP)(2)](PF(6)) has been studied by cyclic voltammetry, and the results are
      consistent with a rapid migration of the proton from the Ni atom of the resulting
      [HNi(PNP)(2)](2+) cation to the N atom to form [Ni(PNP)(PNHP)](2+). Estimates of
      the pK(a) values of the NiH and NH protons of these two isomers indicate that
      proton migration from Ni to N should be favorable by 1-2 pK(a) units. Cyclic
      voltammetry and proton exchange studies of [HNi(depp)(2)](PF(6)) (where depp is
      Et(2)PCH(2)CH(2)CH(2)PEt(2)) are also presented as control experiments that
      support the important role of the bridging N atom of the PNP ligand in the proton
      exchange reactions observed for the various Ni complexes containing the PNP
      ligand. Similarly, structural studies of [Ni(PNBuP)(2)](BF(4))(2) and
      [Ni(PNP)(dmpm)](BF(4))(2) (where PNBuP is Et(2)PCH(2)N(Bu)CH(2)PEt(2) and dmpm is
      Me(2)PCH(2)PMe(2)) illustrate the importance of tetrahedral distortions about Ni
      in determining the hydride acceptor ability of Ni(II) complexes.

PMID- 12513099
TI  - Europium ion catalyzed methanolysis of esters at neutral pH and ambient
      temperature. catalytic Involvement of Eu3+(CH3O-)(CH3OH)x.
AB  - The Eu(3+)-promoted methanolysis of three esters, p-nitrophenyl acetate (1),
      phenyl acetate (2), and ethyl acetate (3) is reported, as well as the
      potentiometric titration of Eu(3+) in MeOH at various [Eu(SO(3)CF(3))(3)]
      (SO(3)CF(3) = OTf). The titration data are analyzed in terms of two ionizations
      corresponding to macroscopic and values, which are respectively defined as the
      values at which the [CH(3)O(-)]/[Eu(3+)] = 0.5 and 1.5. As a function of
      increasing [Eu(OTf)(3)], increases slightly due to a proposed Eu(3+)/(-)OTf ion
      pairing effect, which tends to reduce the acidity of the metal-coordinated
      CH(3)OH, while decreases due to the formation of Eu(3+) dimers and oligomers
      which stabilize the (Eu(3+)(CH(3)O(-))(2))(n)forms through bridging of the
      methoxides between two or more metal ions. For ester 1, a detailed kinetic
      analysis of the reaction rates as a function of both [Eu(OTf)(3)] and in buffered
      methanol reveals that the /second-order rate constant (k(2)) plot for the
      catalyzed reaction follows a bell-shaped profile, suggesting that the active form
      is a Eu(3+)(CH(3)O(-)) monomer with a kinetic of 6.33 +/- 0.06 for formation and
      a of 8.02 +/- 0.10 for its conversion into the inactive (Eu(3+)(CH(3)O(
      ))(2))(n)oligomeric form. At higher values, plots of k(obs) vs [Eu(OTf)(3)] are
      linear at low metal concentration and plateau at higher metal concentration due
      to the formation of inactive higher order aggregates. The Eu(3+)(CH(3)O(-))
      catalysis of the methanolysis of esters 1, 2, and 3 is substantial. Solutions of
      10(-2) M of the catalyst at 7.12 accelerate the reaction relative to the
      methoxide reaction at that by 8 530 000-, 195 000 000- and 7 813 000-fold,
      respectively.

PMID- 12513100
TI  - Different oxidation states of copper(I, I/II, II) thiocyanate complexes
      containing 1,2,4-triazole as a bridging ligand: syntheses, crystal structures,
      and magnetic properties of 2-D polymer Cu I(admtrz)SCN, linear trinuclear
      [CuI2CuII(admtrz)6(SCN)2](ClO4)2, and triangular trinuclear
      [CuII3(admtrz)4(SCN)3(mu3-OH)(H2O)](ClO4)2.H2O (admtrz = 4-amino-3,5-dimethyl
      1,2,4-triazole).
AB  - Copper thiocyanate compounds with three different oxidation states,
      Cu(I)(admtrz)SCN (1), [Cu(I)(2)Cu(II)(admtrz)(6)(SCN)(2)](ClO(4))(2) (2), and
      [Cu(II)(3)(admtrz)(4)(SCN)(3)(mu(3)-OH)(H(2)O)](ClO(4))(2).H(2)O (3), have been
      synthesized and characterized (admtrz = 4-amino-3,5-dimethyl-1,2,4-triazole).
      Compounds 1 and 3 crystallize in the space group Pbca of the orthorhombic system
      with eight formula units in cells of dimensions a = 8.0221(2) A, b = 32.3844(1)
      A, c = 13.5659(3) A, R1/wR2 = 0.0595/0.1674 for compound 1 and a = 21.501(3) A, b
      = 18.382(2) A, c = 21.526(2) A, R1/wR2 = 0.0638/0.1519 for compound 3. Compound 2
      crystallizes in the space group C2/c of the monoclinic system with four formula
      units in cells of dimensions a = 18.772(4) A, b = 11.739(2) A, c = 22.838(5) A,
      beta = 91.11(3) degrees, R1/wR2 = 0.0482/0.1265. The layered-type structure of 1
      can be regarded as constructed from the tetranuclear copper units double bridged
      by one of the two unique thiocyanate and admtrz ligands, which are bridged by the
      other unique thiocyanate ligands to form a two-dimensional layered structure
      along the a and b directions. The linear trinuclear copper cation in mixed
      valence compound 2 consists of one two-valence copper and two one-valence copper
      atoms which are bridged by admtrz ligands, and the external copper(I) atoms are
      coordinated by terminal thiocyanate. The EPR spectra of 2 show the existence of
      localized mixed-valence copper ions. The triangle trinuclear copper cation in
      compound 3 has its Cu(3) triangle capped by one apical mu(3)-OH group, each edge
      bridged by a bridging admtrz ligand and each Cu atom coordinated by a N atom from
      the terminal thiocyanate, while one of the three edges is further bridged by
      another admtrz ligand and the opposite Cu1 atom is coordinated by a water
      molecule. The EPR and magnetic susceptibility of compound 3 were studied, showing
      antiferromagnetic behavior.

PMID- 12513101
TI  - Migratory insertion of hydrogen isocyanide in the
      pentacyano(methyl)cobaltate(III) anion.
AB  - The preparation of the pentacyano(iminiumacetyl)cobaltate(III) anion and its N
      methyl and N,N-dimethyl derivatives is reported. The iminiumacetyl group is
      formed by migratory insertion of cis hydrogen isocyanide in the
      pentacyano(methyl)cobaltate(III) anion. The new compounds have been
      spectroscopically characterized by (1)H, (13)C, (15)N, and (59)Co NMR
      spectroscopy and by absorption spectroscopy. The iminium carbon atoms yield (13)C
      NMR signals at 256.7, 247.7, and 240.4 ppm for the parent iminiumacetyl compound
      and its N-methyl and N,N-dimethyl derivatives, respectively. The (15)N resonance
      frequencies of the iminium groups and the lack of rotation of the carbon-nitrogen
      bond both show that this bond is best described as a double bond. The structure
      of (Et(4)N)(Ph(4)As)(2)[Co(CN)(5)(CH(3))] was determined by X-ray crystallography
      at 122.0(5) K. The structure displays disorder.

PMID- 12513102
TI  - Adolescent smoking: epidemiology and approaches for achieving cessation.
AB  - The initiation of smoking typically occurs during adolescence. To date, most
      adolescent smoking control efforts have focused on prevention; attempting to
      identify and influence factors that contribute to experimentation and initiation.
      However, given the large number of adolescent smokers, it is important that
      effort also be directed toward facilitating cessation. Many adolescents are
      addicted to cigarettes and report withdrawal symptoms that are similar to those
      experienced by adults. Relapse rates are high; few adolescents who try to quit on
      their own are successful. Clinician-delivered smoking cessation interventions
      have a positive impact in adults and should be applied to adolescents to promote
      and sustain abstinence. Although pharmaceutical aids for cessation have been
      shown to be well tolerated and effective in adults, less is known about their use
      in adolescents. As such, clinicians are encouraged to explore whether
      pharmaceutical aids have been approved for use in adolescents in their country
      and to use discretion when considering their use in patients <18 years of age.
      Because pediatricians are in a unique position to facilitate tobacco cessation
      counseling, they should routinely ask their patients whether they use tobacco,
      advise users to quit, assess readiness to quit, assist with quitting, and arrange
      follow-up counseling. Tobacco cessation efforts can be enhanced by teaming with
      other health professionals (e.g. nurses, dentists, pharmacists, social workers)
      or worksite and community-based organizations that provide health promotion
      services.

PMID- 12513103
TI  - Spasticity associated with cerebral palsy in children: guidelines for the use of
      botulinum A toxin.
AB  - Botulinum A toxin produces selective and reversible chemodenervation that can be
      employed to balance muscle forces across joints in children with cerebral palsy
      (CP). Currently, there are two commercially available botulinum A toxin
      formulations (BOTOX) and Dysport). The amount of botulinum A toxin required
      depends upon the number of muscles that are targeted, and the size of the
      patient. In order to achieve adequate chemodenervation with botulinum A toxin,
      the following conditions must be met: (i) a sufficient number of units of toxin
      must be injected in order to neutralize neuromuscular junction (NMJ) activity;
      (ii) an appropriate drug volume is required in order to optimize the delivery of
      the toxin to the NMJs; and (iii) localization of the injecting needle through the
      fascia of the target muscle is necessary. Localization of the injection may be
      facilitated by active electromyography, ultrasonography, palpation of the muscle
      belly, and/or use of anatomic landmarks. Botulinum A toxin injections are
      indicated for use in pediatric patients with CP to: (i) improve motor function by
      balancing muscle forces across joints; (ii) improve health-related quality of
      life by decreasing spasticity and/or decreasing caregiver burden; (iii) decrease
      pain from spasticity; (iv) enhance self-esteem by diminishing inappropriate motor
      responses; and (v) provide a presurgical diagnostic tool. Following intramuscular
      injections of botulinum A toxin, short-term benefits of reduced spasticity are
      observed in approximately 70-82% of children. The intermediate term (1-2 years)
      efficacy rate is approximately 50%. The most common deformity treated with toxin
      injections in pediatric patients with CP is equinus foot deformity. However,
      efficacy of toxin injections for the management of crouched gait, pelvic flexion
      contracture, cervical spasticity, seating difficulties, and upper extremity
      deformity also has been documented. In addition, toxin injections have been shown
      to manage painful muscle spasticity associated with surgery or application of
      casts and painful cervical spasticity with or without dystonia. Toxin injections
      can also be used as a diagnostic tool to determine the appropriateness of other
      interventions by observing the muscle response to the injection in order to gain
      additional information for the development of a treatment plan. Botulinum A
      toxin, when used in appropriate doses, is well tolerated.

PMID- 12513104
TI  - The use of proton pump inhibitors in children: a comprehensive review.
AB  - Proton pump inhibitors (PPIs) belong to a group of chemically related compounds
      whose primary function is the inhibition of acid production in the final common
      metabolic pathway of gastric parietal cells. PPIs are highly selective and
      effective in their action and have few short- or long-term adverse effects. These
      pharmacologic features have made the development of PPIs the most significant
      advancement in the management of acid peptic related disorders in the last two
      decades. There are numerous published adult studies that describe the
      pharmacology, efficacy and safety of these anti-secretory agents; however, in the
      pediatric population, there are very few comparable studies, particularly
      multicenter studies with significant patient enrollment. In preparing this
      article, our aim was to perform a comprehensive review of the literature on the
      clinical pharmacology and use of PPIs in the pediatric population, and to briefly
      review some recent articles. Relevant literature was identified by performing
      MEDLINE/Pubmed searches from January 1990 to December 2001. Combinations of the
      following search terms were use to analyze these databases: proton pump
      inhibitor, children, pediatrics, gastroesophageal reflux disease (GERD),
      esophagitis, intestinal metaplasia, Helicobacter pylori, omeprazole,
      lansoprazole, pantoprazole, rabeprazole, esomeprazole, and safety. Abstracts from
      the 14th annual conference of the North American Society for Pediatric
      Gastroenterology, Hepatology and Nutrition (NASPGHAN) 2001, and the Disease and
      Digestive Week 2001, were also included in the review. All pediatric studies
      reviewed were limited to either omeprazole or lansoprazole. The dosage range used
      for the management of GERD and related disorders with lansoprazole was 0.73-1.66
      mg/kg/day (maximum 30 mg/day). The dosage range for GERD management using
      omeprazole was 0.3-3.5 mg/kg (maximum 80 mg/day). The dosage range for omeprazole
      used for H. pylori was 0.5-1.5 mg/kg/day, with a maximum dosage of 40 mg/day, and
      lansoprazole-containing regimens for H. pylori eradication used dosages ranging
      from 0.6-1.2 mg/kg/day, with a maximum dosage of 30 mg/day. Few severe adverse
      events were reported with the use of either drug. Eradication rates for H. pylori
      were 56-87% for lansoprazole-based triple therapy, and 75-94% for omeprazole
      based eradication regimens. To date, there are no published controlled trials of
      sufficient power comparing the efficacy of the five commercially available PPIs
      in children, for a variety of acid peptic diseases. Studies suggest that PPIs are
      highly effective for the management of GERD and related disorders, and are a
      critically needed component of triple therapy to eradicate H. pylori. PPIs have a
      very good tolerability profile in adults and children, but long-term tolerability
      studies are needed, particularly in the pediatric population. Multicenter studies
      are critically needed to evaluate the second-generation PPIs, to compare PPI
      efficacy to each other, and to assess the importance of developmental and genetic
      pharmacology of these drugs in children with acid-peptic disease.

PMID- 12513105
TI  - Quality of life in children and adolescents with cystic fibrosis: implications
      for optimizing treatments and clinical trial design.
AB  - Health related quality of life (QOL) as an outcome measure in clinical trials is
      becoming increasingly important. Trials should not only be able to demonstrate
      the pharmacologic activity of a therapy, but of equal importance, they should
      demonstrate clinical effectiveness that is of significant benefit to the patient.
      QOL measurement provides a way of incorporating the child/parent's perspective of
      how cystic fibrosis (CF) and its therapies impact on their lives. Several
      validated generic instruments have been employed to measure QOL in adolescents
      and adults. QOL assessment is more difficult in children and, therefore, has been
      employed less often in children with CF. Difficulties arise with the issue of
      whether children can report their own experiences directly, or whether a parent
      or clinician should report on behalf of the child. A child-centered approach is
      imperative since the literature indicates that children are able to report on
      their own QOL. An additional complication has been the use of adult measures with
      children. These are often inappropriate in their complexity, use of language,
      response scales, and time frame. The evaluation of pharmacologic therapies can
      profit from QOL measurement. The effectiveness of a drug and any adverse effects
      that impact on daily life can be assessed from the child/parent's viewpoint. Home
      therapy versus hospital therapy and drug delivery systems, are additional areas
      where QOL as an outcome measure is valuable. There have been relatively few
      appropriately powered trials in CF, and only a minority of these have evaluated
      QOL as an outcome measure. This review highlights areas where QOL measurement is
      appropriate. It focuses on the pharmacologic trials that have employed QOL
      assessment for antibiotic, mucociliary clearance, anti-inflammatory, and
      nutritional therapies. Methodological issues of incorporating QOL assessment into
      trials center on cross-cultural and data interpretation issues. QOL measurement
      in CF has been patchy and largely unreliable. The notion that improved symptoms
      equate with improved QOL is erroneous. Measurement of how symptoms impact on QOL
      is essential. Currently, the development and validation of CF specific measures
      (across the CF age range) provides optimism for appropriate QOL measurement in
      clinical trials, and for future meta-analysis and systematic reviews.

PMID- 12513106
TI  - Lansoprazole: in the management of gastroesophageal reflux disease in children.
AB  - Lansoprazole, a proton pump inhibitor, inactivates the H(+)/K(+)-ATPase pump in
      parietal cells, thereby suppressing basal and stimulated gastric acid secretion
      and increasing intragastric pH. After 8-12 weeks' treatment with lansoprazole,
      all children (n = 27) with esophagitis at baseline were healed (confirmed by
      endoscopy) and 76% of 62 evaluable children experienced improvements in overall
      gastroesophageal reflux disease (GERD) symptoms. In this noncomparative trial, 66
      children (aged 1-11 years) with GERD with or without esophagitis received oral
      lansoprazole 15 or 30 mg once daily dependent on their weight. The drug is
      generally well tolerated in children with GERD. In the largest study, the most
      common treatment-related adverse events occurring during therapy were
      constipation and headache.

PMID- 12513109
TI  - Formoterol delivered by Turbuhaler: in pediatric asthma.
AB  - Formoterol is an inhaled long-acting beta(2)-adrenoceptor agonist, with a rapid
      onset of action and a bronchodilator effect that lasts for at least 12 hours. As
      add-on therapy to anti-inflammatory medication (e.g. corticosteroids), formoterol
      4.5 and 9 microg twice daily delivered by Turbuhaler for 3 months significantly
      improved lung function (change from baseline in forced expiratory volume in 1
      second and/or peak expiratory flow) compared with placebo in randomised, double
      blind trials in pediatric patients (aged 6-17 years). In addition, formoterol 9
      microg twice daily for 12 weeks reduced the use of rescue medication compared
      with salmeterol 50 microg twice daily in a nonblind trial in pediatric patients
      (aged 7-16 years). Single-dose formoterol 4.5 or 9 microg delivered by Turbuhaler
      provided significant prophylaxis against exercise-induced bronchoconstriction
      compared with placebo, and demonstrated a longer duration of effect than
      terbutaline, in a randomized, double-blind, crossover trial in pediatric patients
      (aged 8-17 years). Formoterol delivered by Turbuhaler was well tolerated in
      pediatric patients, with respiratory infection being the most commonly reported
      adverse event.

PMID- 12513112
TI  - Colorectal cancer in the elderly: is palliative chemotherapy of value?
AB  - Colorectal cancer is a disease of the elderly, with 70% of patients being aged 65
      years or older. In Western countries, the total number of elderly patients with
      this disease is expected to further increase in the future. Since the incidence
      of adverse physical or socioeconomic conditions in the elderly is higher than in
      younger patients, a thorough assessment of the patient's suitability for therapy
      should be performed before a decision is made. Using a Comprehensive Geriatric
      Assessment (CGA) to subdivide the population of elderly cancer patients into
      three groups can help to guide treatment decisions. Both in the adjuvant and in
      the palliative setting, there are sufficient data supporting the use of
      fluorouracil-based chemotherapy in fit elderly patients who can tolerate
      cytotoxic treatment. Systemic chemotherapy has been shown to effectively reduce
      mortality in the adjuvant situation and to be of clinical benefit for patients
      with metastatic disease in terms of longer survival, control of symptoms and
      quality of life. In recent years, new substances such as oxaliplatin or
      irinotecan have shown significant activity in the treatment of patients with
      metastatic colorectal cancer. However, information on how to guide the use of
      these new drugs in elderly patients is still lacking. Limited data from clinical
      trials indicate treatment efficacy in selected elderly patients comparable to
      that observed in younger patients, with overall manageable toxicity. Clearly,
      further clinical trials in elderly patients with colorectal cancer are necessary
      as well as the incorporation of aspects of geriatric medicine into the teaching
      programme of medical oncologists.

PMID- 12513113
TI  - Beta-blockers after acute myocardial infarction in elderly patients with diabetes
      mellitus: time to reassess.
AB  - Beta-blockers effectively reduce mortality and recurrent cardiovascular events in
      patients surviving myocardial infarction. However, these agents are underused in
      clinical practice, especially in older patients with diabetes mellitus. The
      current literature shows that beta-blockers are at least as effective in older
      diabetic patients as in other patients, without major safety concerns for their
      possible adverse effects. The use of these agents in clinical practice should
      therefore be encouraged, in order to reduce the burden of cardiovascular
      mortality and morbidity in older diabetic patients post-infarction.

PMID- 12513115
TI  - Inflammatory pancreatic diseases in older patients: recognition and management.
AB  - The aging process influences and modifies the clinical picture and treatment
      modalities of inflammatory pancreatic diseases in elderly patients. The two major
      categories of inflammatory exocrine pancreatic diseases seen in the elderly are
      acute pancreatitis (AP) and chronic pancreatitis (CP). In elderly patients with
      AP, the presence of concomitant diseases affecting renal, hepatic and
      cardiopulmonary function make the early clinical assessment of the severity of AP
      inaccurate at the time of admission to hospital. In addition, the classical
      multifactorial scoring system routinely utilised in clinical practice to
      determine the severity of AP may overscore elderly patients because increasing
      age is associated with more points. Contrast-enhanced computed tomography is
      particularly useful in assessing the severity of AP and is required in all
      patients suspected with severe AP. It should be repeated after a certain time
      period to monitor the disease. The most important aspect of the management of
      elderly patients with severe AP is the prevention and treatment of systemic and
      local complications. Treatment of AP should address the removal of aetiological
      factor(s) and support of organ systems and hydroelectrolytic/caloric balance;
      specific treatments (antiproteases, antibacterials) should also be administered
      to patients with severe AP. Surgery is indicated mainly when infection occurs
      following pancreatic necrosis and/or fluid collection. However, in selected
      patients with a high anaesthetic risk, alternative, less invasive drainage
      options (percutaneous, endoscopic) should be considered. CP rarely occurs in
      older age, and it should be suspected based on clinical findings. The greatest
      challenge is the differentiation between CP and pancreatic cancer. Treatment of
      CP in the elderly should be directed at controlling the symptoms, by management
      of diabetes and exocrine insufficiency because pain and complications are rare in
      elderly patients with CP. Compliance with treatment should be periodically
      assessed if insulin and/or oral enzyme supplementation is required. Careful
      evaluation of nutritional status and its prompt correction is also important.

PMID- 12513114
TI  - Demographics, assessment and management of pain in the elderly.
AB  - The prevalence of pain increases with each decade of life. Pain in the elderly is
      distinctly different from pain experienced by younger individuals. Cancer is a
      leading cause of pain; however, other conditions that cause pain such as facet
      joint arthritis (causing low back pain), polymyalgia rheumatica, Paget's disease,
      neuropathies, peripheral vascular disease and coronary disease most commonly
      occur in patients over the age of 50 years. Poorly controlled pain in the elderly
      leads to cognitive failure, depression and mood disturbance and reduces
      activities of daily living. Barriers to pain management include a sense of
      fatalism, denial, the desire to be 'the good patient', geographical barriers and
      financial limitations. Aging causes physiological changes that alter the
      pharmacokinetics and pharmacodynamics of analgesics, narrowing their therapeutic
      index and increasing the risk of toxicity and drug-drug interactions. CNS changes
      lead to an increased risk of delirium. Assessment among the verbal but
      cognitively impaired elderly is satisfactorily accomplished with the help of
      unidimensional and multidimensional pain scales. A comprehensive physical
      examination and pain history is essential, as well as a review of cognitive
      function and activities of daily living. The goal of pain management among the
      elderly is improvement in pain and optimisation of activities of daily living,
      not complete eradication of pain nor the lowest possible drug dosages. Most
      successful management strategies combine pharmacological and nonpharmacological
      (home remedies, massage, topical agents, heat and cold packs and informal
      cognitive strategies) therapies. A basic principle of the pharmacological
      approach in the elderly is to start analgesics at low dosages and titrate slowly.
      The WHO's three-step guideline to pain management should guide prescribing.
      Opioid choices necessitate an understanding of pharmacology to ensure safe
      administration in end-organ failure and avoidance of drug interactions. Adjuvant
      analgesics are used to reduce opioid adverse effects or improve poorly controlled
      pain. Adjuvant analgesics (NSAIDs, tricyclic antidepressants and antiepileptic
      drugs) are initiated prior to opioids for nociceptive and neuropathic pain.
      Preferred adjuvants for nociceptive pain are short-acting paracetamol
      (acetaminophen), NSAIDs, cyclo-oxygenase-2 inhibitors and corticosteroids (short
      term). Preferred drugs for neuropathic pain include desipramine, nortriptyline,
      gabapentin and valproic acid. Drugs to avoid are pentazocine, pethidine
      (meperidine), dextropropoxyphene and opioids that are both an agonist and
      antagonist, ketorolac, indomethacin, piroxicam, mefenamic acid, amitriptyline and
      doxepin. The type of pain, and renal and hepatic function, alter the preferred
      adjuvant and opioid choices. Selection of the appropriate analgesics is also
      influenced by versatility, polypharmacy, severity and type of pain, drug
      availability, associated symptoms and cost.

PMID- 12513116
TI  - Differential pharmacokinetics of theophylline in elderly patients.
AB  - The clinical use of theophylline as a first-line bronchodilator has declined
      during the last two decades. However, in many clinical settings, such as an
      emergency bronchial asthma attack, theophylline may have a first-line role, in
      combination with beta(2)-adrenoreceptor agonists and corticosteroids, for
      improving the asthmatic status. Furthermore, many therapeutic mechanisms of
      theophylline for bronchial asthma have been reported, and recent studies have
      suggested that theophylline therapy may have a beneficial role in the management
      of chronic stable asthma as well as exacerbated disease. However, theophylline
      has a low therapeutic index because the bronchodilation it produces has a linear
      relationship with logarithmic increases in serum concentration for the
      therapeutic range of 5-20 mg/L. Thus, the knowledge of its basic pharmacokinetics
      and the factors that can alter its clearance is clinically relevant for
      physicians. Especially when used in elderly asthmatic patients, dosage adjustment
      of theophylline is a requisite since the elderly have several risk factors that
      may increase the plasma theophylline level, such as reduced clearance, various
      underlying diseases and multiple coadministered drugs. After theophylline
      treatment has been initiated, therapeutic drug monitoring is required.

PMID- 12513117
TI  - Spontaneous establishment of a novel Japanese macaque cell line with epithelial
      cell phenotypes.
AB  - A novel macaque cell line (J3K) with epithelial phenotypes was spontaneously
      established from a kidney specimen of a Japanese macaque (Macaca fuscata). Its
      population doubling level reached more than 500, and it was regarded as an
      established permanent cell line. J3K cells have transformed cell phenotypes such
      as loss of contact inhibition and anchorage-independent cell growth. Unlike other
      monkey adherent cell lines, J3K had no SV40 large T antigen. After establishment,
      cells have constantly expressed telomerase activity, whereas telomere length has
      been maintained. No mutations in the coding regions of the p53 complementary
      deoxyribonucleic acid were detected in the late-passaged cells. J3K, a novel
      transformed epithelial cell line, will be useful material for the comparative
      study of human and other primate cellular aging as well as cancer cell biology.

PMID- 12513118
TI  - Biphasic culture strategy based on hyperosmotic pressure for improved humanized
      antibody production in Chinese hamster ovary cell culture.
AB  - Hyperosmotic pressure increased specific antibody productivity (q(Ab)) of
      recombinant Chinese hamster ovary (rCHO) cells (SH2-0.32) and it depressed cell
      growth. Thus, the use of hyperosmolar medium did not increase the maximum
      antibody concentration substantially. To overcome this drawback, the feasibility
      of biphasic culture strategy was investigated. In the biphasic culture, cells
      were first cultivated in the standard medium with physiological osmolality (294
      mOsm/kg) for cell growth. When cells reached the late exponential growth phase,
      the spent standard medium was replaced with the fresh hyperosmolar medium (522
      mOsm/kg) for antibody production. The q(Ab) in growth phase with the standard
      medium was 2.1 microg per 10(6) cells/d, whereas the q(Ab) in antibody production
      phase with the hyperosmolar medium was 11.1 microg per 10(6) cells/d. Northern
      blot analysis showed a positive relationship between the relative contents of
      intracellular immunoglobulin messenger ribonucleic acid and q(Ab). Because of the
      enhanced q(Ab) and the increased cell concentration in biphasic culture, the
      maximum antibody concentration obtained in biphasic culture with 522 mOsm/kg
      medium exchange was 161% higher than that obtained in batch culture with the
      standard medium. Taken together, the simple biphasic culture strategy based on
      hyperosmotic culture is effective in improving antibody production of rCHO cells.

PMID- 12513119
TI  - Exposure to oxidized low-density lipoprotein reduces activable Ras protein in
      vascular endothelial cells.
AB  - Oxidized low-density lipoprotein (ox-LDL) has been shown to alter the migratory
      and proliferative activities of the vascular endothelial cells (EC) in response
      to serum and growth factors. The mechanism underlying the antiproliferative
      effect of ox-LDL on vascular EC has not been fully elucidated. In this report, we
      show that exposure of vascular EC to ox-LDL results in a marked reduction of the
      membrane-associated Ras protein. Further study shows that in ox-LDL-treated EC,
      reduction of the membrane-associated Ras protein is correlated with a reduced
      amount of active Ras (Ras-guanosine triphosphate), indicating that the Ras
      signaling pathway is attenuated. The attenuation of the Ras signaling pathway in
      ox-LDL-treated EC may thus be responsible for the retarded response to the
      mitogenic stimulation of serum and growth factors.

PMID- 12513120
TI  - Epithelial and fibroblast cell lines derived from a spontaneous mammary carcinoma
      in a MMTV/neu transgenic mouse.
AB  - Female murine mammary tumor virus (MMTV)/neu transgenic mice, expressing a wild
      type rat neu oncogene driven by an MMTV promoter, develop focal mammary
      adenocarcinomas that are pathologically very similar to human breast tumors. Two
      new cell lines were established from a mammary tumor that arose in a female
      MMTV/neu transgenic mouse. One of these lines, mammary carcinoma from Neu
      transgenic mouse A (MCNeuA), has an epithelial morphology, is cytokeratin
      positive, and expresses high levels of the neu transgene. Karyotyping and
      comparative genomic hybridization analyses demonstrated genomic alterations in
      the MCNeuA cell line. The other line, N202Fb3, has a fibroblast morphology, is
      cytokeratin negative, and expresses the neu transgene at a very low level. This
      cell line also expresses smooth muscle alpha-actin, suggesting that it is a
      myofibroblast line. The MCNeuA cell line is tumorigenic when injected into
      syngeneic MMTV/neu transgenic mice, with an in vivo doubling time of about 14 d.
      The rationale for establishing this tumor cell line was to provide a tumor
      transplantation system for rapidly assessing immunotherapeutic interventions
      before testing in the more cumbersome model of spontaneous tumor development in
      the MMTV/neu transgenic mice. Mice immunized with a Neu extracellular domain
      protein vaccine were protected against a subsequent inoculation of MCNeuA cells,
      indicating that this cell line will be useful for evaluating cancer vaccine
      strategies. This tumor cell line may also prove useful in studying the biological
      properties of the neu oncogene and its role in the malignant process. In
      addition, the tumor-derived fibroblast line may be useful for studying tumor
      stromal cell interactions.

PMID- 12513121
TI  - Primitive endothelial cell lines from the porcine embryonic yolk sac.
AB  - Endothelial cell lines have been established from cells that were isolated from
      porcine yolk sacs from day 18 and day 22 embryos and propagated in vitro under
      various growth conditions. After expansion in vitro, the general properties of
      the cells proved similar for the different media used. The endothelial cells
      expressed cell surface receptors for acetylated low-density lipoprotein and also
      expressed cell surface-associated angiotensin-converting enzyme. The cells showed
      a characteristically high level of binding for Bandeiraea simplicifolia lectin I
      and Dolichos biflorus agglutinin but did not bind significant amounts of Ulex
      europaeus lectin I. The cells expressed low but serologically detectable levels
      of Class I major histocompatibility complex (MHC) antigens but failed to bind
      antibodies directed against Class II MHC antigens. Alpha5beta1 integrins were
      weakly expressed, whereas vascular cell adhesion molecule-1 (CD106) and
      alphavbeta3 integrins were not detected. Three-dimensional tube formation was
      readily observed in cultures grown on Matrigel and occurred even in uncoated
      plastic dishes in the absence of Matrigel. In contrast to most of the adult
      porcine endothelial cells, yolk sac-derived endothelial cells did not possess
      serologically detectable receptors for porcine growth hormone (GH), an
      observation consistent with the finding that GH did not increase the
      proliferative rate of these cells. Electron microscopic examination demonstrated
      the presence of Weibel-Palade bodies, tight endothelial cell junctions, and
      typical rough endoplasmic reticulum. Exposure of the cells to either concanavalin
      A-stimulated porcine splenocyte culture supernatants or to human tumor necrosis
      factor alpha did not cause upregulation of VCAM-1 or Class II MHC antigens.
      Addition of porcine interferon-gamma led to an increase in the level of
      expression of Class I MHC. Yolk sac endothelial cells from day 22 embryos showed
      a low but detectable level of expression of Class II MHC antigens, whereas the
      endothelial cells from day 18 embryos showed no expression of Class II antigens
      after interferon-gamma stimulation. The cells maintained competence to develop
      vascular structures in vitro and could do so after coinjection with murine tumor
      cells into adult, immunocompromised mice.

PMID- 12513122
TI  - Rhythmicity of engraftment and altered cell cycle kinetics of cytokine-cultured
      murine marrow in simulated microgravity compared with static cultures.
AB  - Space flight with associated microgravity is complicated by "astronaut's anemia"
      and other hematologic abnormalities. Altered erythroid differentiation, red cell
      survival, plasma volume, and progenitor numbers have been reported. We studied
      the impact of microgravity on engraftable stem cells, culturing marrow cells in
      rotary wall vessel (RWV) culture chambers mimicking microgravity and in normal
      gravity nonadherent Teflon bottles. A quantitative competitive engraftment
      technique was assessed under both conditions in lethally irradiated hosts. We
      assessed 8-wk engraftable stem cells over a period spanning at least one cell
      cycle for cytokine (FLT-3 ligand, thrombopoietin [TPO], steel factor)-activated
      marrow stem cells. Engraftable stem cells were supported out to 56 h under
      microgravity conditions, and this support was superior to that seen in normal
      gravity Teflon bottle cultures out to 40 h, with Teflon bottle culture support
      superior to RWV from 40 to 56 h. A nadir of stem cell number was seen at 40 h in
      Teflon and 48 h in RWV, suggesting altered marrow stem cell cycle kinetics under
      microgravity. This is the first study of engraftable stem cells under
      microgravity conditions, and the differences between microgravity and normal
      gravity cultures may present opportunities for unique future stem cell expansion
      strategies.

PMID- 12513123
TI  - Modulation of adipocyte determination and differentiation-dependent factor 1 by
      selected polyunsaturated fatty acids.
AB  - The transcription factor, sterol regulatory binding protein 1c (also called
      adipocyte determination and differentiation-dependent factor 1), stimulates
      transcription of the messenger ribonucleic acids (mRNAs) for lipid synthesis
      enzymes. Hepatic ADD1 transcripts are reduced by polyunsaturated fatty acids
      (PUFAs). The ADD1 transcripts are expressed to a considerable extent in porcine
      adipocytes. Consequently, it was of interest to examine the effects of several
      PUFAs on ADD1 in a tissue wherein several long-chain fatty acids (FAs) increase
      adipocyte differentiation. The effects of arachidonic acid (C20:4),
      docosahexaenoic acid (C22:6), and cis 9, trans 11-conjugated linoleic acid (9,11
      CLA) on differentiating preadipocyte ADD1 mRNA and protein and on preadipocyte
      differentiation were determined. Porcine stromal-vascular cells were plated in
      serum-containing medium and differentiated in serum-free medium containing
      insulin, hydrocortisone, and transferrin +/- an individual FA. After 24-h
      differentiation +/- FA, plates were stained with Oil Red O as an indicator of
      differentiation or total RNA was extracted or a nuclear fraction was isolated for
      protein measurement. Addition of C20:4 or 9,11-CLA increased the number of Oil
      Red O-stained cells or the Oil Red O-stained material, whereas C22:6 did not.
      Addition of C20:4, C22:6, or 9,11-CLA decreased the concentration of the mRNA and
      protein for ADD1. Thus, although all three FAs decreased the ADD1 mRNA and
      protein concentrations, C20:4 and 9,11-CLA increased differentiation, measured by
      Oil Red O staining, whereas C22:6 did not. The data suggest that the regulation
      of differentiation and mRNAs by individual FAs may involve distinct mechanisms.

PMID- 12513124
TI  - H-Type 1 carbohydrate antigen expression by ovine endometrial cells.
AB  - Our objective was to determine whether H-Type 1 carbohydrate antigen is expressed
      by ovine endometrial epithelial cells. Endometrium was obtained from sheep on
      days (D) 1, 5, 11, 13, and 15 of the estrous cycle or pregnancy and D17 and D19
      of pregnancy. Immunofluorescence microscopy of frozen tissue sections revealed
      intense staining on the apical surface of glandular uterine epithelial (GE) cells
      from D11 to D17 of pregnancy. Light punctate staining of luminal uterine
      epithelial (LE) cells was present from D15 to D19 of pregnancy, with isolated
      areas of intense staining observed only on D15 of pregnancy. There were no
      noticeable differences in staining patterns on equivalent d of the estrous cycle.
      Immortalized sheep LE and GE cells were used to determine whether estradiol (E),
      progesterone (P), or E + P, with or without interferon tau (IFNtau), regulates H
      Type 1 antigen expression in vitro. Intermittent punctate surface staining was
      observed on both cell lines independent of steroid treatment. Treatment with P or
      IFNtau increased H-Type 1 antigen expression (P < 0.01) and resulted in large
      aggregates of punctate staining. Domain-specific biotinylation and Western
      blotting of cell lysates from LE and GE cells were used to identify proteins
      carrying the H-Type 1 antigen. For both cell types, major immunoreactive apical
      membrane proteins were detected at 31, 33, 42, 55, 60, and 70 kDa. Therefore, the
      H-type 1 antigen is expressed mainly on GE cells during pregnancy recognition in
      utero and up-regulated by P and IFNtau on LE and GE cells in vitro.

PMID- 12513125
TI  - Fibroblast and epidermal growth factors modulate proliferation and neural cell
      adhesion molecule expression in epithelial cells derived from the adult mouse
      tongue.
AB  - Lingual epithelial cells, including those of the taste buds, are regularly
      replaced by proliferative stem cells. We found that integrin beta(1), a
      keratinocyte stem cell marker, was expressed at the basal layer and taste buds of
      adult mouse tongue epithelium. We purified and cultured integrin beta(1)-positive
      cells (termed KT-1 cells), whose growth was stimulated by epidermal growth factor
      (EGF) and basic fibroblast growth factor (FGF-2). FGF-2 stimulation induced
      translocation of the FGF type I receptor (FGFR1) into nuclei, suggesting that the
      growth-stimulating effect of FGF-2 was mediated through FGFR1. EGF and FGF-2 also
      regulated cell surface expression of the neural cell adhesion molecule (N-CAM) in
      KT-1 cells. Anti-N-CAM antibody immunoreactivity was restricted to the gustatory
      epithelium and the nerves in the tongue epithelium, giving rise to the
      possibility that KT-1 may contain gustatory epithelial cells. KT-1 cells may thus
      be useful for analyzing the factors that regulate the growth and differentiation
      of lingual and gustatory epithelial cells in vitro.

PMID- 12513126
TI  - Lowering of the kinetic energy in interacting quantum systems.
AB  - Interactions never lower the ground state kinetic energy of a quantum system
      below the noninteracting value. However, at nonzero temperature, where the system
      occupies a thermal distribution of states, interactions can reduce the kinetic
      energy. This can be demonstrated from a first order weak coupling expansion.
      Simulations (both variational and restricted path integral Monte Carlo) of the
      electron gas model and dense hydrogen confirm this and show that in contrast to
      the ground state case, at nonzero temperature the population of low momentum
      states can be increased relative to the free Fermi distribution. This effect is
      not seen in simulations of liquid 3He.

PMID- 12513127
TI  - Existence of long-range order for trapped interacting bosons.
AB  - We derive an inequality governing "long-range" order for a localized Bose
      condensed state, relating the condensate fraction at a given temperature with
      effective curvature radius of the condensate and total particle number. For the
      specific example of a one-dimensional, harmonically trapped dilute Bose
      condensate, it is shown that the inequality gives an explicit upper bound for the
      Thomas-Fermi condensate size which may be tested in current experiments.

PMID- 12513128
TI  - Noise-sustained spiral waves: effect of spatial and temporal memory.
AB  - We have investigated the constructive roles of temporal noise, spatial disorder,
      and spatiotemporal fluctuation on the formation of spiral waves. Noise-sustained
      spiral waves are observed, the order of which passes a maximum with the increment
      of noise intensity, showing spatiotemporal coherent resonance. Moreover, we find
      that spatiotemporal fluctuation is much more favorable for the ordering process
      than temporal-noise only or spatial-disorder only. We demonstrate that this
      phenomenon shows the disadvantageous effect of spatial or temporal memory of
      noise.

PMID- 12513129
TI  - Determination of hyperfine-induced transition rates from observations of a
      planetary nebula.
AB  - Observations of the planetary nebula NGC3918 made with the STIS instrument on the
      Hubble Space Telescope reveal the first unambiguous detection of a hyperfine
      induced transition 2s2p 3P(o)(0)-->2s2 1S0 in the berylliumlike emission line
      spectrum of N IV at 1487.89 A. A nebular model allows us to confirm a transition
      rate of 4x10(-4) sec(-1)+/-33% for this line. The measurement represents the
      first independent confirmation of the transition rate of hyperfine-induced lines
      in low ionization stages, and it provides support for the techniques used to
      compute these transitions for the determination of very low densities and isotope
      ratios.

PMID- 12513130
TI  - Scattering of cosmic rays by magnetohydrodynamic interstellar turbulence.
AB  - Recent advances in understanding of magnetohydrodynamic (MHD) turbulence call for
      substantial revisions in our understanding of cosmic ray transport. We use
      recently obtained scalings of MHD modes to calculate the scattering frequency for
      cosmic rays. We consider gyroresonance with MHD modes (Alfvenic, slow, and fast)
      and transit-time damping by fast modes. We conclude that the gyroresonance with
      fast modes is the dominant contribution to cosmic ray scattering for the typical
      interstellar conditions. In contrast to earlier studies, we find that Alfvenic
      and slow modes are inefficient because they are far from the isotropy usually
      assumed.

PMID- 12513131
TI  - The inflationary perturbation spectrum.
AB  - Motivated by the prospect of testing inflation from precision cosmic microwave
      background observations, we present analytic results for scalar and tensor
      perturbations in single-field inflation models, based on the application of
      uniform approximations. This technique is systematically improvable, possesses
      controlled error bounds, and does not rely on assuming the slow-roll parameters
      to be constant. We provide closed form expressions for the power spectra and the
      corresponding scalar and tensor spectral indices.

PMID- 12513132
TI  - A class of exact classical solutions to string theory.
AB  - We show that the recently obtained class of spacetimes for which all of the
      scalar curvature invariants vanish (which can be regarded as generalizations of
      pp-wave spacetimes) are exact solutions in string theory to all perturbative
      orders in the string tension scale. As a result the spectrum of the theory can be
      explicitly obtained, and these spacetimes are expected to provide some hints for
      the study of superstrings on more general backgrounds. Since these Lorentzian
      spacetimes suffer no quantum corrections to all loop orders they may also offer
      insights into quantum gravity.

PMID- 12513136
TI  - Octupole vibration in superdeformed 152(66)Dy86.
AB  - Nine transitions of dipole character have been identified linking an excited
      superdeformed (SD) band in 152Dy to the yrast SD band. As a result, the
      excitation energy of the lowest level in the excited SD band has been measured to
      be 14 238 keV. This corresponds to a 1.3 MeV excitation above the SD ground
      state. The levels in this band have tentatively been determined to be of negative
      parity and odd spin. The measured properties are consistent with an
      interpretation in terms of a rotational band built on a collective octupole
      vibration.

PMID- 12513137
TI  - Severe inhibition of fusion by quasifission in reactions forming 220Th.
AB  - Evaporation residue cross sections have been measured following the fusion of 16O
      with 204Pb, forming the compound nucleus 220Th. These are compared with existing
      data for the same compound nucleus formed following fusion reactions with 40Ar,
      48Ca, 82Se, and 124Sn projectiles. At energies where the reduced cross sections
      of xn evaporation residues would be expected to be the same for all reactions,
      those for the heavier projectiles are typically a factor of 10 smaller than those
      for 16O. This inhibition is attributed to strong competition of quasifission with
      fusion at the low angular momenta associated with evaporation residue formation.

PMID- 12513135
TI  - Measurements of inclusive B-->psi production.
AB  - Using the combined CLEO II and CLEO II.V data sets of 9.1 fb(-1) at the
      Upsilon(4S), we measure properties of psi mesons produced directly from decays of
      the B meson, where "B" denotes an admixture of B+, B-, B0, and B;(0), and "psi"
      denotes either J/psi(1S) or psi(2S). We report first measurements of psi
      polarization in B-->psi(direct)X: alpha(psi(1S))=-0.30(+0.07)(-0.06)+/-0.04 and
      alpha(psi(2S))=-0.45(+0.22)(-0.19)+/-0.04. We also report improved measurements
      of the momentum distributions of psi produced directly from B decays, correcting
      for measurement smearing. Finally, we report measurements of the inclusive
      branching fraction for B-->psiX and B-->chi(c1)X.

PMID- 12513138
TI  - Observation of cumulative spatial focusing of atoms.
AB  - We report an experimental study of the spatial distribution of ultracold cesium
      atoms exposed to a series of kicks from a standing wave of light. We observe
      cumulative focusing, leading to a spatial array of atoms which is of interest for
      atomic lithography. To observe the spatial distribution, we developed a free
      space measurement technique that enables the reconstruction of the atomic motion
      as a function of time. We find increased focusing of atoms after as many as ten
      kicks, and the results are in good agreement with theoretical predictions.

PMID- 12513139
TI  - QED radiative corrections to parity nonconservation in heavy atoms.
AB  - The self-energy and vertex QED radiative corrections [approximately
      Zalpha2f(Zalpha)] are shown to give a large negative contribution to the parity
      nonconserving (PNC) amplitude in heavy atoms. The correction -0.73(20)% found for
      the 6s-7s PNC amplitude in 133Cs brings the experimental result for this
      transition into agreement with the standard model. The calculations are based on
      a new relation that expresses the radiative corrections to the PNC matrix element
      via corrections to the energy shifts induced by the finite nuclear size.

PMID- 12513133
TI  - Limits on extra dimensions and new particle production in the exclusive photon
      and missing energy signature in pp collisions at square root [s]=1.8 TeV.
AB  - The exclusive gammaE(T) signal has a small standard model cross section and is
      thus a channel sensitive to new physics. This signature is predicted by models
      with a superlight gravitino or with large extra spatial dimensions. We search for
      such signals at the Collider Detector at Fermilab, using 87 pb(-1) of data at
      square root [s]=1.8 TeV, and extract 95% C.L. limits on these processes. A limit
      of 221 GeV is set on the scale |F|(1/2) in supersymmetric models. For 4, 6, and 8
      extra dimensions, model-dependent limits on the fundamental mass scale M(D) of
      0.55, 0.58, and 0.60 TeV, respectively, are found. We also specify a "pseudo
      model-independent" method of comparing the results to theoretical predictions.

PMID- 12513140
TI  - Radiative corrections and parity nonconservation in heavy atoms.
AB  - The self-energy and the vertex radiative corrections to the effect of parity
      nonconservation in heavy atoms are calculated analytically in orders Zalpha2 and
      Z2alpha3ln((lambda(C)/r(0)), where lambda(C) and r(0) are the Compton wavelength
      and the nuclear radius, respectively. The sum of the radiative corrections is 
      0.85% for Cs and -1.41% for Tl. Using these results, we have performed analysis
      of the experimental data on atomic parity nonconservation. The values obtained
      for the nuclear weak charge, Q(W)=-72.90(28)exp(35)theor for Cs, and Q(W)=
      116.7(1.2)exp(3.4)(theor) for Tl, agree with predictions of the standard model.
      As an application of our approach, we have also calculated analytically the
      dependence of the Lamb shift on the finite size of the nucleus.

PMID- 12513141
TI  - Rotational quenching in ionic systems at ultracold temperatures.
AB  - The behavior of the rotational quenching for a molecular ion in collision with
      closed-shell neutral gases is investigated. We confirm that Wigner's threshold
      law for inelastic scattering holds in the presence of a long-range interaction
      due to polarization forces decreasing as the inverse fourth power of the distance
      but find that, because of the contributions of the higher angular momenta, its
      range of applicability is markedly reduced when compared to the scattering by
      neutral species. The calculations of the quenching cross sections make evident
      the special features of ionic systems at ultralow collision energies and yield
      rate coefficients of the order of 10(-9) x cm(3) x s(-1), much larger than those
      found for the quenching of neutral molecules.

PMID- 12513142
TI  - Feshbach resonances in rubidium 87: precision measurement and analysis.
AB  - More than 40 Feshbach resonances in rubidium 87 are observed in the magnetic
      field range between 0.5 and 1260 G for various spin mixtures in the lower
      hyperfine ground state. The Feshbach resonances are observed by monitoring the
      atom loss, and their positions are determined with an accuracy of 30 mG. In a
      detailed analysis, the resonances are identified and an improved set of model
      parameters for the rubidium interatomic potential is deduced. The elastic width
      of the broadest resonance at 1007 G is predicted to be significantly larger than
      the magnetic-field resolution of the apparatus. This demonstrates the potential
      for applications based on tuning the scattering length.

PMID- 12513143
TI  - State-to-State integral cross section for the H+H2O-->H2+OH abstraction reaction.
AB  - The initial state selected time-dependent wave-packet method was extended to
      calculate the state-to-state integral cross section for the title reaction with
      H2O in the ground rovibrational state on the potential energy surface of Yang,
      Zhang, Collins, and Lee. One OH bond length was fixed in the study, which is
      justifiable for the abstraction reaction, but the remaining 5 degrees of freedom
      were treated exactly. It was found that the H2 molecule is produced vibrationally
      cold for collision energy up to 1.6 eV. The OH rotation takes away about 4% of
      total available energy in the products, while the fraction of energy going to H2
      rotation increases with collision energy to about 20% at 1.6 eV.

PMID- 12513134
TI  - Measurements of branching fractions and CP-violating asymmetries in B0-->pi+pi-,
      K+pi-, K+K- decays.
AB  - We present measurements of branching fractions and CP-violating asymmetries for
      two-body neutral B meson decays to charged pions and kaons based on a sample of
      about 88x10(6) Upsilon(4S)-->BB decays. From a time-independent fit we measure
      the charge-averaged branching fractions B(B0-->pi+pi-)=(4.7+/-0.6+/-0.2)x10(-6),
      B(B0-->K+pi-)=(17.9+/-0.9+/-0.7)x10(-6), and the direct CP-violating charge
      asymmetry A(Kpi)=-0.102+/-0.050+/-0.016 [-0.188,-0.016], where the ranges in
      square brackets indicate the 90% confidence intervals. From a time-dependent fit
      we measure the B0-->pi+pi- CP-violating parameters S(pipi)=0.02+/-0.34+/-0.05 [
      0.54,+0.58] and C(pipi)=-0.30+/-0.25+/-0.04 [-0.72,+0.12].

PMID- 12513144
TI  - Negative mass instability for interacting particles in a 1D box: theory and
      application.
AB  - We demonstrate that the synchronization effect observed [Pedersen et al., Phys.
      Rev. Lett. 87, 055001 (2001)]], when a bunch of ions oscillates between two
      mirrors in an electrostatic ion beam trap, can be explained as a negative mass
      instability. We derive simple necessary conditions for the existence of a regime
      in which this dispersionless behavior occurs and demonstrate that in this regime,
      the ion trap can be used as a high resolution mass spectrometer.

PMID- 12513145
TI  - Nonclassicality of quantum states: a hierarchy of observable conditions.
AB  - A necessary and sufficient hierarchy of conditions is derived that is completely
      equivalent to the failure of the Glauber-Sudarshan P function to be a probability
      density. The conditions are formulated in terms of experimentally accessible
      characteristic functions of quadratures.

PMID- 12513146
TI  - Bragg scattering of free electrons using the Kapitza-Dirac effect.
AB  - Bragg scattering has been observed for free electrons using a standing wave of
      light. Both the rocking curve and the angular electron distribution have been
      measured. The results of a numerical simulation to the Schrodinger equation are
      consistent with our experimental data. Unlike the diffraction regime which uses
      thin crystals, the Bragg regime requires the use of thick crystals. We point out
      several applications in atom optics that could be realized in electron optics.

PMID- 12513147
TI  - One-dimensional optically bound arrays of microscopic particles.
AB  - A one-dimensional optically coupled array of colloidal particles is created in a
      potential well formed by two counterpropagating Gaussian light beams. This array
      has analogies to linear chains of trapped atomic ions. Breathing modes and
      oscillations of the center of mass are observed. The stability of the array is in
      accordance with the Kramers model.

PMID- 12513148
TI  - Unidirectional optical pulse propagation equation.
AB  - A unidirectional optical pulse propagation equation, derived directly from
      Maxwell's equations, provides a seamless transition between various nonlinear
      envelope equations in the literature and the full vector Maxwell's equations. The
      equation is illustrated in the context of supercontinuum generation in air and is
      compared to a recent scalar model of Brabec and Krausz. Fully vectorial aspects
      of the model are illustrated in the context of extreme focusing of a femtosecond
      pulse.

PMID- 12513149
TI  - Measuring the electric field of few-cycle laser pulses by attosecond cross
      correlation.
AB  - A new technique for directly measuring the electric field of linearly polarized
      few-cycle laser pulses is proposed. Based on the solution of the time-dependent
      Schrodinger equation (TDSE) for an H atom in the combined field of infrared (IR)
      femtosecond (fs) and ultraviolet (UV) attosecond (as) laser pulses we show that,
      as a function of the time delay between two pulses, the difference (or
      equivalently, asymmetry) of photoelectron signals in opposite directions (along
      the polarization vector of laser pulses) reproduces very well the profile of the
      electric field (or vector potential) in the IR pulse. Such ionization asymmetry
      can be used for directly measuring the carrier-envelope phase difference (i.e.,
      the relative phase of the carrier frequency with respect to the pulse envelope)
      of the IR fs laser pulse.

PMID- 12513150
TI  - Long time algebraic relaxation in chaotic billiards.
AB  - The long-time algebraic relaxation process in spatially periodic billiards with
      infinite horizon is shown to display a self-similar time-asymptotic form. This
      form is identical for a class of such billiards, but can be different in an
      important special case.

PMID- 12513151
TI  - Fidelity decay as an efficient indicator of quantum chaos.
AB  - We demonstrate that a system's rate of fidelity decay under repeated
      perturbations may be measured efficiently on a quantum information processor, and
      analyze the conditions under which this indicator is a reliable probe of quantum
      chaos. The type and rate of the decay are not dependent on the eigenvalue
      statistics of the unperturbed system, but depend on the system's eigenvector
      statistics in the eigenbasis of the perturbation. For random eigenvector
      statistics, the decay is exponential with a rate fixed by the variance of the
      perturbation's energy spectrum. Hence, even classically regular models can
      exhibit an exponential fidelity decay under generic quantum perturbations. These
      results clarify which perturbations can distinguish classically regular and
      chaotic quantum systems.

PMID- 12513152
TI  - Tailoring wavelets for chaos control.
AB  - Chaos is a class of ubiquitous phenomena and controlling chaos is of great
      interest and importance. In this Letter, we introduce wavelet controlled dynamics
      as a new paradigm of dynamical control. We find that by modifying a tiny fraction
      of the wavelet subspaces of a coupling matrix, we could dramatically enhance the
      transverse stability of the synchronous manifold of a chaotic system. Wavelet
      controlled Hopf bifurcation from chaos is observed. Our approach provides a
      robust strategy for controlling chaos and other dynamical systems in nature.

PMID- 12513153
TI  - Vortex statistics from Eulerian and Lagrangian time series.
AB  - Coherent vortices are an important component of the dynamics of geophysical
      turbulence, but direct estimates of the properties of the vortex population from
      measured data is usually difficult. Motivated by this problem, we propose a new
      method for determining the statistical properties of coherent vortices in two
      dimensional turbulence based on a small number of Lagrangian and Eulerian time
      series. The method provides reliable estimates of the mean vortex size and vortex
      number density.

PMID- 12513154
TI  - Spallation ultracold-neutron production in superfluid helium.
AB  - The first ultracold-neutron (UCN) production in superfluid helium placed in a
      spallation neutron source is carried out. A UCN density of 0.7 UCN/cm(3), which
      can be used in experiments, is achieved for a proton-beam power of 78 W and a He
      II temperature of 1.2 K. The present new UCN source is not limited by Liouville's
      theorem and extraction losses, which were serious problems in the previous
      sources. The present source has the possibility of extremely high-density UCN
      production compared with previous UCN sources.

PMID- 12513155
TI  - Atomistic mechanism for hot spot initiation.
AB  - We propose a picture of the role of shock-wave interactions with microscopic
      voids that leads to significant heating, sufficient to thermally initiate
      chemical reactions in solid explosives, or phase transitions in metals. The key
      ingredients to this dramatic overshoot in temperature are: (i) a strong enough
      shock wave to cause vaporization of material into the void; (ii) the stagnation
      of low-density vapor (for a wide enough gap) at the far side; and (iii)
      recompression of the gas (pressure-volume work) from low density back to the
      original shocked density. We explore dependencies on both shock strength and one
      dimensional gap width in atomistic simulations of a two-dimensional unreactive
      Lennard-Jones solid, comparing observed thermal overshoot with a straightforward
      model, to show how hot spots can be generated under shock-wave conditions.

PMID- 12513156
TI  - Structure of high-density amorphous ice under pressure.
AB  - We report in situ neutron diffraction studies of high-density amorphous ice (HDA)
      at 100 K at pressures up to 2.2 GPa. We find that the compression is achieved by
      a strong contraction ( approximately 20%) of the second neighbor coordination
      shell, so that at 2.2 GPa it closely approaches the first coordination shell,
      which itself remains intact in both structure and size. The hydrogen bond
      orientations suggest an absence of hydrogen bonding between first and second
      shells and that HDA has increasingly interpenetrating hydrogen bond networks
      under pressure.

PMID- 12513157
TI  - Direct separation of short range order in intermixed nanocrystalline and
      amorphous phases.
AB  - Diffraction anomalous fine-structure (DAFS) and extended x-ray absorption fine
      structure (EXAFS) measurements were combined to determine short range order (SRO)
      about a single atomic type in a sample of mixed amorphous and nanocrystalline
      phases of germanium. EXAFS yields information about the SRO of all Ge atoms in
      the sample, while DAFS determines the SRO of only the ordered fraction. We
      determine that the first-shell distance distribution is bimodal; the
      nanocrystalline distance is the same as the bulk crystal, to within 0.01(2) A,
      but the mean amorphous Ge-Ge bond length is expanded by 0.076(19) A. This
      approach can be applied to many systems of mixed amorphous and nanocrystalline
      phases.

PMID- 12513158
TI  - High amplitude, ultrashort, longitudinal strain solitons in sapphire.
AB  - We demonstrate the development of high-amplitude picosecond strain pulses in a
      sapphire single crystal into an ultrafast compressional soliton train. For this
      purpose, large-intensity light pulses were used to excite a metal film, yielding
      a 2 orders of magnitude higher strain than that achieved in earlier studies.
      Propagation of the packets is monitored over a distance of several millimeters by
      means of Brillouin light scattering. A one-parameter model, based on the Korteweg
      de Vries-Burgers equation, simultaneously explains the observed behavior at all
      strains and temperatures under study. We predict up to 11 solitons in the train,
      reaching pressures as high as 40 kbar and 0.5 ps temporal widths.

PMID- 12513159
TI  - Structure, properties, and dynamics of oxygen vacancies in amorphous SiO2.
AB  - Oxygen vacancies in SiO2 have long been regarded as bistable, forming a Si-Si
      dimer when neutral and a puckered configuration when positively charged. We
      report first-principles calculations of O vacancies in amorphous SiO2 supercells
      that unveil significantly more complex behavior. We find that the vast majority
      of O vacancies do not pucker after capture of a hole, but are shallow traps. The
      remaining vacancies exhibit two distinct types of puckering. Upon capturing an
      electron, one type forms a metastable dipole, while the other collapses to a
      dimer. A statistical distribution of O vacancies is obtained, and the
      implications for charge transport and trapping in SiO2 are discussed.

PMID- 12513160
TI  - Cluster-beam deposition and in situ characterization of carbyne-rich carbon
      films.
AB  - Nanostructured carbon films produced by supersonic cluster beam deposition have
      been studied by in situ Raman spectroscopy. Raman spectra show the formation of a
      sp2 solid with a very large fraction of sp-coordinated carbyne species with a
      long-term stability under ultrahigh vacuum. Distinct Raman contributions from
      polyyne and cumulene species have been observed, as well as different stabilities
      under gas exposure. Our experiments confirm theoretical predictions and
      demonstrate the possibility of producing a carbyne-rich pure carbon solid. The
      stability of the sp2-sp network has important implications for astrophysics and
      for the production of novel carbon-based systems.

PMID- 12513161
TI  - Thermal glass transition beyond the Vogel-Fulcher-Tammann behavior for glass
      forming diglycidylether of bisphenol A.
AB  - For the low molecular weight fragile liquid diglycidyl ether of bisphenol A we
      report, based on Brillouin and dielectric spectroscopy, on a thermal glass
      transition where the relaxation time of the alpha process does not go to
      infinity. Instead, the structural alpha relaxation disappears spontaneously at
      the transition point. That discontinuity in relaxation time coincides with a kink
      in the longitudinal hypersonic velocity and determines unambiguously the
      transition from the liquid to the glassy state.

PMID- 12513162
TI  - First-order transitions for n-vector models in two and more dimensions: rigorous
      proof.
AB  - We prove that various SO(n)-invariant n-vector models with interactions which
      have a deep and narrow enough minimum have a first-order transition in the
      temperature. The result holds in dimensions two or more and is independent of the
      nature of the low-temperature phase.

PMID- 12513163
TI  - Anomalous isotopic effect on the lattice parameter of silicon.
AB  - The difference Delta(a)=a(30)-a(28) of the lattice parameter of 30Si and 28Si
      crystals is measured over a temperature range from 4.7 to 700 K. In disagreement
      with existing knowledge, the strongest isotopic effect is not detected at the
      lowest achieved temperature T=4.7 K. An anomalous behavior is observed: The
      relative difference |Delta(a)/a| attains its maximum value of 56.8(5) ppm at
      T=75(10) K. The anomalous behavior is attributed to the influence of phonon modes
      with negative Gruneisen parameters. At T=700 K the effect still amounts to 30% of
      the maximal value. The experimental data are consistent with an approach based on
      the density-functional perturbation theory.

PMID- 12513164
TI  - Filling transition: exact results for Ising corners.
AB  - We obtain the exact solution for a two-dimensional rectangular Ising ferromagnet
      forming a corner with a surface field applied to the spins on edges. We establish
      the existence of the filling transition and give the condition for the filling
      temperature. We discuss the basic properties of the transition.

PMID- 12513165
TI  - Fundamental influence of C on adhesion of the Al2O3/Al interface.
AB  - Our first-principles computations indicate that the clean Al2O3/Al interface is
      relatively weak-weaker than bulk Al. Fracture experiments reveal that the
      interface is relatively strong with observed failure in bulk Al, however. This
      paradox is resolved via doping effects of the common impurity C. We have found
      that only 1/3 of a monolayer of carbon segregated to the interface can increase
      the work of separation by a factor of 3. The resulting strong interface is
      consistent with fracture experiments. It arises due to void formation in the
      interface, which provides low-strain sites for the carbon to segregate to. The
      degree of void formation is consistent with the relatively high heat of oxide
      formation of Al.

PMID- 12513166
TI  - Effects of short-range attraction in metal epitaxial growth.
AB  - The effects of short-range attraction in metal epitaxial growth are studied. Our
      results indicate that even at normal incidence, the short-range attraction of
      depositing atoms to step edges can significantly increase the selected mound
      angle and surface roughness for typical energies used in epitaxial growth. Our
      results also lead to a picture of the process of deposition near step edges that
      is quite different from the standard downward funneling picture. Results for the
      dependence of the uphill current on incident atom kinetic energy and substrate
      temperature are also presented.

PMID- 12513167
TI  - p(2x2) phase of buckled dimers of Si(100) observed on n-type substrates below 40
      K by scanning tunneling microscopy.
AB  - We have investigated the basic surface reconstruction of Si(100) on well defined
      surfaces fabricated on various substrates at low temperatures (-80 K) by scanning
      tunneling microscopy. Below 40 K, the single p(2x2) phase, a phase never observed
      before, was observed exclusively on n-type substrates doped in the range of 0.002
      to 0.017 Omega cm. We also exclude the possibility of the (2x1) symmetric dimer
      commonly observed at low temperature (-10 K) being the basic surface
      reconstruction by showing that a buckled dimer can be flip-flopped by the
      tunneling tip.

PMID- 12513168
TI  - Dispersive electron transport in tris(8-hydroxyquinoline) aluminum (Alq3) probed
      by impedance spectroscopy.
AB  - Electron transport in tris(8-hydroxyquinoline) aluminum (Alq3) is investigated by
      impedance spectroscopy under conditions of space-charge limited conduction
      (SCLC). Existing SCLC models are extended to include the field dependence of the
      charge carrier mobility and energetically distributed trap states. The dispersive
      nature of electron transport is revealed by a frequency-dependent mobility with a
      dispersion parameter alpha in the range 0.4-0.5, independent of temperature. This
      indicates that positional rather than energetic disorder is the dominant
      mechanism for the dispersive transport of electrons in Alq3.

PMID- 12513169
TI  - Ultrasharp magnetization steps in perovskite manganites.
AB  - We report a detailed study of steplike metamagnetic transitions in
      polycrystalline Pr0.5Ca0.5Mn0.95Co0.05O3. The steps have a sudden onset below a
      critical temperature, are extremely sharp (width <2x10(-4) T), and occur at
      critical fields which are linearly dependent on the absolute value of the cooling
      field in which the sample is prepared. Similar transitions are also observed at
      low temperature in non-Co doped manganites, including single crystal samples.
      These data show that the steps are an intrinsic property, qualitatively different
      from either previously observed higher temperature metamagnetic transitions in
      the manganites or metamagnetic transitions observed in other materials.

PMID- 12513170
TI  - Optical response of two-dimensional electron fluids beyond the kohn regime:
      strong nonparabolic confinement and intense laser light.
AB  - We investigate the linear and nonlinear optical response of two-dimensional
      interacting electron fluids confined by a strong nonparabolic potential. We show
      that such fluids may exhibit higher-harmonic spectra under realistic experimental
      conditions. Higher harmonics arise as the electrons explore anharmonicities of
      the confinement potential (electron-electron interactions reduce this nonlinear
      effect). This opens the possibility of controlling the optical functionality by
      engineering the confinement potential. Our results were obtained within time
      dependent density-functional theory. A classical hydrodynamical model is in good
      agreement with the quantum-mechanical results.

PMID- 12513171
TI  - Quantum electronic transport through a precessing spin.
AB  - The conductance through a local nuclear spin precessing in a magnetic field is
      studied by using the equations-of-motion approach. The characteristics of the
      conductance is determined by the tunneling matrix and the position of equilibrium
      chemical potential. We find that the spin-flip coupling between the electrons on
      the spin site and the leads produces the conductance oscillation. When the spin
      is precessing in the magnetic field at Larmor frequency (omegaL), the conductance
      develops the oscillation with the frequency of both omegaL and 2omegaL
      components, the relative spectrum weight of which can be tuned by the chemical
      potential and the spin-flip coupling.

PMID- 12513172
TI  - Spin-dependent transport through an interacting quantum dot.
AB  - We study the nonequilibrium spin transport through a quantum dot coupled to the
      magnetic electrodes. A formula for the spin-dependent current is obtained and is
      applied to discuss the linear conductance and magnetoresistance in the
      interacting regime. We show that the Kondo resonance and the correlation-induced
      spin splitting of the dot levels may be systematically controlled by internal
      magnetization in the electrodes. As a result, when the electrodes are in parallel
      magnetic configuration, the linear conductance is characterized by two spin
      resolved peaks. Furthermore, the presence of the spin-flip process in the dot
      splits the Kondo resonance into three peaks.

PMID- 12513173
TI  - Gaussian superconducting fluctuations, thermal transport, and the nernst effect.
AB  - We calculate the contribution of superconducting fluctuations to thermal
      transport in the normal state, at low magnetic fields. We do so in the Gaussian
      approximation to their critical dynamics which is also the Aslamazov-Larkin
      approximation in the microscopics. Our results for the thermal conductivity
      tensor and the transverse thermoelectric response are new. The latter compare
      favorably with the data of Ong and collaborators on the Nernst effect in the
      cuprates.

PMID- 12513174
TI  - Impurity bound states in disordered d-wave superconductors.
AB  - Recent STM experiments on Bi2Sr2Ca2Cu3O10 observed sharp bound states associated
      with Zn and Ni impurities, as previously predicted theoretically. Here we extend
      the theory to the case of a finite concentration of impurities. Using the
      nonlocal coherent potential approximation, we show that the resonance peak both
      broadens and shifts as a function of impurity concentration.

PMID- 12513175
TI  - High magnetic field studies of the hidden order transition in URu2Si2.
AB  - We studied in detail the low temperature/high magnetic field phases of URu2Si2
      single crystals with specific heat, magnetocaloric effect, and magnetoresistance
      in magnetic fields up to 45 T. Data obtained down to 0.5 K, and extrapolated to
      T=0, show a suppression of the hidden-order phase at H0(0)=35.9+/-0.35 T and the
      appearance of a new phase for magnetic fields in excess of H1(0)=36.1+/-0.35 T
      observed only at temperatures lower than 6 K. In turn, complete suppression of
      this high field state is attained at a critical magnetic field H2(0)=39.7+/-0.35
      T. No phase transitions are observed above 40 T. We discuss our results in the
      context of itinerant versus localized f electrons.

PMID- 12513176
TI  - Discrete change of spin-density-wave modulation in Cr(100)/Sn multilayers as a
      function of Cr layer thickness.
AB  - Magnetic structures of epitaxial Cr(001)/Sn multilayers, where monatomic Sn
      layers are periodically embedded in a Cr(001) film, were studied using neutron
      diffraction and Mossbauer spectroscopy. It was found that spin-density-wave (SDW)
      antiferromagnetic structures with the modulation along the perpendicular
      direction to the film plane are stabilized at low temperatures. The wavelength of
      the SDW discretely changes as a function of the superlattice period. The enhanced
      magnetic moments of Cr at the Cr/Sn interfaces are thought to pin the antimode of
      the SDW modulation at the interface, resulting in the SDW with the modulation
      harmonic to the superlattice period.

PMID- 12513177
TI  - Universal scaling of ballistic magnetoresistance in magnetic nanocontacts.
AB  - We show that ballistic magnetoresistance exhibits universal scaling in atomic or
      nanometer scale contacts. Plotting the data as conductance, we find that, if the
      maximum magnetoconductance is normalized to unity and the conductance is scaled
      with the conductivity of the bulk material, the data fall in a narrow region,
      independent of the nanocontact materials, for our four data sets and four from
      the literature. The results agree with a theory that takes into account spin
      scattering within a magnetic-domain wall.

PMID- 12513178
TI  - Ultrafast quenching of the antiferromagnetic order in FeBO3: direct optical
      probing of the phonon-magnon coupling.
AB  - The dynamics of the optically induced phase transition from the antiferromagnetic
      to the paramagnetic state in FeBO3 is observed using a pump-probe magneto-optical
      Faraday technique employing 100 fs laser pulses. At the pump energy of 1.55 eV
      phonon-assisted transitions dominate in the absorption of light and ultrafast
      heating of the lattice occurs. The quenching of the magnetic order is caused by
      an increase of the magnon temperature due to energy transfer from the heated
      lattice. The heating time of the magnon system is around 700 ps, which is a
      factor of 20 faster than previously reported phonon-magnon interaction times.

PMID- 12513179
TI  - Laser action of trions in a semiconductor quantum well.
AB  - We report on the observation of optical gain and lasing at the trion transition
      of n-doped ZnSe quantum wells. Specifically, the (stimulated) emission-absorption
      net rate of this transition is controlled by the difference of trion and electron
      occupation in momentum space. As the mass of the trion is larger than that of the
      electron, gain occurs on the low-energy side of the line center without
      degeneracy and inversion in the total particle numbers. The scenario is
      reminiscent of a three-level system. At higher injection levels, carrier heating
      sets on and limits the available gain to values of about 10(4) cm(-1).

PMID- 12513180
TI  - Nonlinear effects from dipolar interactions in hyperpolarized liquid 129Xe.
AB  - We investigate nonlinear effects of long-range dipolar interactions in a
      spherical sample of hyperpolarized liquid 129Xe. Using two high-T(c) SQUID
      detectors we directly measure the evolution of the magnetization gradients. For
      small initial rf tip angles we observe an increase in the transverse relaxation
      time T2* by a factor of 5 and coherent oscillations of magnetization gradients.
      For large tip angles we observe an exponential growth of the magnetization
      gradients and demonstrate a gain in sensitivity to magnetic field gradients by a
      factor of 10. Our results are in quantitative agreement with simple analytical
      predictions. We discuss applications of these nonlinear effects for precision
      measurements.

PMID- 12513181
TI  - Response of spiking neurons to correlated inputs.
AB  - The effect of a temporally correlated afferent current on the firing rate of a
      leaky integrate-and-fire neuron is studied. This current is characterized in
      terms of rates, autocorrelations, and cross correlations, and correlation time
      scale tau(c) of excitatory and inhibitory inputs. The output rate nu(out) is
      calculated in the Fokker-Planck formalism in the limit of both small and large
      tau(c) compared to the membrane time constant tau of the neuron. By simulations
      we check the analytical results, provide an interpolation valid for all tau(c),
      and study the neuron's response to rapid changes in the correlation magnitude.

PMID- 12513182
TI  - Diversity within a birdsong.
AB  - We present a model for the activities of neural circuits in a nucleus found in
      the brains of songbirds: the robust nucleus of the archistriatum (RA). This is a
      fore brain song control nucleus responsible for the phasic and precise neural
      signals driving vocal and respiratory motor neurons during singing. Driving a
      physical model of the avian vocal organ with the signals generated by the neural
      model, we produce synthetic songs. This allows us to show that certain
      connectivity architectures in the RA give rise to a wide range of different
      vocalizations under simple excitatory instructions.

PMID- 12513183
TI  - Solvable senescence model showing a mortality plateau.
AB  - We present some analytic results for the steady states of the Penna model of
      senescence, generalized to allow genetically identical individuals to die at
      different ages via an arbitrary survival function. Modeling this with a Fermi
      function (of modest width) we obtain a clear mortality plateau late in life:
      something that has so far eluded explanation within such mutation accumulation
      models. This suggests that factors causing variable mortality within genetically
      identical subpopulations, which include environmental effects, may be essential
      to understanding the mortality plateau seen in many real species.

PMID- 12513184
TI  - Photoinduced flip-flop of amphiphilic molecules in lipid bilayer membranes.
AB  - We demonstrate localized photoinduced flip-flop of stilbazolium markers in model
      lipid bilayer membranes. The flip-flop mechanism and dynamics are determined by
      combined two-photon excited fluorescence and second-harmonic generation
      microscopy. Upon illumination of labeled membranes with a femtosecond laser beam,
      two-photon absorption induced photoisomerization provokes a significant increase
      in the cis- marker population whose flip-flop rate was determined to be at least
      a thousand times faster than that for transmarkers, allowing the possibility of
      fast targeted control of the local interleaflet distribution of markers in
      biological membranes.

PMID- 12513185
TI  - Complex extension of quantum mechanics.
AB  - Requiring that a Hamiltonian be Hermitian is overly restrictive. A consistent
      physical theory of quantum mechanics can be built on a complex Hamiltonian that
      is not Hermitian but satisfies the less restrictive and more physical condition
      of space-time reflection symmetry (PT symmetry). One might expect a non-Hermitian
      Hamiltonian to lead to a violation of unitarity. However, if PT symmetry is not
      spontaneously broken, it is possible to construct a previously unnoticed symmetry
      C of the Hamiltonian. Using C, an inner product whose associated norm is positive
      definite can be constructed. The procedure is general and works for any PT
      symmetric Hamiltonian. Observables exhibit CPT symmetry, and the dynamics is
      governed by unitary time evolution. This work is not in conflict with
      conventional quantum mechanics but is rather a complex generalization of it.

PMID- 12513186
TI  - Quantum entanglement of moving bodies.
AB  - We study the properties of quantum entanglement in moving frames, and show that,
      because spin and momentum become mixed when viewed by a moving observer, the
      entanglement between the spins of a pair of particles is not invariant. We give
      an example of a pair, fully spin entangled in the rest frame, which has its spin
      entanglement reduced in all other frames. Similarly, we show that there are pairs
      whose spin entanglement increases from zero to maximal entanglement when boosted.
      While spin and momentum entanglement separately are not Lorentz invariant, the
      joint entanglement of the wave function is.

PMID- 12513187
TI  - Stability of quantum states of finite macroscopic systems against classical
      noises, perturbations from environments, and local measurements.
AB  - We study the stability of quantum states of macroscopic systems of finite volume
      V. By using both the locality and huge degrees of freedom, we show the following:
      (i) If square fluctuation of every additive operator is O(V) or less for a pure
      state, then it is not fragile for any weak classical noises or weak perturbations
      from environments. (ii) If square fluctuation of some additive operator is O(V2)
      for a pure state, then it is fragile for some of these. (iii) If a state, pure or
      mixed, has the "cluster property," then it is stable against local measurements,
      and vice versa. Among many applications, we discuss the mechanism of symmetry
      breaking in finite systems.

PMID- 12513188
TI  - Bose-Einstein condensation into nonequilibrium States studied by condensate
      focusing.
AB  - We report the formation of Bose-Einstein condensates into nonequilibrium states.
      Our condensates are much longer than equilibrium condensates with the same number
      of atoms, show strong phase fluctuations, and have a dynamical evolution similar
      to that of quadrupole shape oscillations of regular condensates. The condensates
      emerge in elongated traps as the result of local thermalization when the
      nucleation time is short compared to the axial oscillation time. We introduce
      condensate focusing as a new method to extract the phase-coherence length of Bose
      Einstein condensates.

PMID- 12513189
TI  - A radiation scalar for numerical relativity.
AB  - This Letter describes a scalar curvature invariant for general relativity with a
      certain, distinctive feature. While many such invariants exist, this one vanishes
      in regions of space-time which can be said unambiguously to contain no
      gravitational radiation. In more general regions which incontrovertibly support
      nontrivial radiation fields, it can be used to extract local, coordinate
      independent information partially characterizing that radiation. While a clear,
      physical interpretation is possible only in such radiation zones, a simple
      algorithm can be given to extend the definition smoothly to generic regions of
      space-time.

PMID- 12513190
TI  - Topological defects in contracting universes.
AB  - We study the behavior and consequences of cosmic string networks in contracting
      universes. They approximately behave during the collapse phase as radiation
      fluids. Scaling solutions describing this are derived and tested against high
      resolution numerical simulations. A string network in a contracting universe,
      together with the gravitational radiation it generates, can affect the dynamics
      of the universe both locally and globally and be an important source of
      radiation, entropy, and inhomogeneity. We discuss possible implications for
      bouncing and cyclic models.

PMID- 12513191
TI  - Realistic Dirac leptogenesis.
AB  - We present a model of leptogenesis that preserves lepton number. The model
      maintains the important feature of more traditional leptogenesis scenarios: The
      decaying particles that provide the CP violation necessary for baryogenesis also
      provide the explanation for the smallness of the neutrino Yukawa couplings. This
      model clearly demonstrates that, contrary to conventional wisdom, neutrinos need
      not be Majorana in nature in order to help explain the baryon asymmetry of the
      universe.

PMID- 12513192
TI  - Convergence of the linear delta expansion in the critical O(N) field theory.
AB  - The linear delta expansion is applied to the three-dimensional O(N) scalar field
      theory at its critical point in a way that is compatible with the large-N limit.
      For a range of the arbitrary mass parameter, the linear delta expansion for <phi-
      >(2)> converges, with errors decreasing as a power of the order n in delta. If
      the principal of minimal sensitivity is used to optimize the convergence rate,
      the errors seem to decrease exponentially with n.

PMID- 12513193
TI  - Implications on supersymmetry-breaking mediation mechanisms from observing Bs-
      >mu+mu- and the muon g-2.
AB  - We consider B(s)-->mu(+)mu(-) and the muon (g-2)(mu) in various supersymmetry
      breaking mediation mechanisms. If the decay B(s)-->mu(+)mu(-) is observed at
      Tevatron Run II with a branching ratio larger than approximately 2 x 10(-8), the
      noscale supergravity (including the gaugino mediation), the gauge mediation
      scenario with a small number of messenger fields and low messenger scale, and a
      class of anomaly mediation scenarios will be excluded, even if they can
      accommodate a large muon (g-2)(mu). On the other hand, the minimal supergravity
      scenario and similar mechanisms derived from string models can accommodate this
      observation.

PMID- 12513194
TI  - The reaction gammap-->pi0gamma'p and the magnetic dipole moment of the Delta+
      1232 resonance.
AB  - The reaction gammap-->pi(0)gamma'p has been measured with the TAPS calorimeter at
      the Mainz Microtron accelerator facility MAMI for energies between sqrt[s]=1221
      1331 MeV. The cross section's differential in angle and energy have been
      determined for the photon gamma' in three bins of the excitation energy. This
      reaction channel provides access to the magnetic dipole moment of the
      Delta(+)(1232) resonance and, for the first time, a value of
      mu(Delta(+))=[2.7(+1.0)(-1.3)(stat)+/-1.5(syst)+/-3(theor)]mu(N) has been
      extracted.

PMID- 12513195
TI  - Generalized spin polarizabilities of the nucleon in heavy-baryon chiral
      perturbation theory at order Omicron(p(4)).
AB  - We present the first heavy-baryon chiral perturbation theory calculation at order
      Omicron(p(4)) for the spin-dependent amplitudes for virtual Compton scattering
      off the nucleon and extract the Omicron(p(4)) results for the generalized spin
      polarizabilities of the nucleon.

PMID- 12513196
TI  - Decisive role of fragmentation functions in hard hadron production.
AB  - It is demonstrated that the fragmentation functions at large momentum fraction
      play a key role in hard hadron production from relativistic proton-proton
      collisions. We find that this region of the fragmentation functions is not
      strongly constrained by the electron-positron data. This freedom can be used
      (together with the transverse-momentum distribution of partons) to reproduce hard
      pion-to-proton ratio data in relativistic proton-proton collisions.

PMID- 12513198
TI  - Measurements of ultracold-neutron lifetimes in solid deuterium.
AB  - We present the first measurements of the survival time of ultracold neutrons
      (UCNs) in solid deuterium (SD2). This critical parameter provides a fundamental
      limitation to the effectiveness of superthermal UCN sources that utilize solid
      ortho-deuterium as the source material. These measurements are performed
      utilizing a SD2 source coupled to a spallation source of neutrons, providing a
      demonstration of UCN production in this geometry and permitting systematic
      studies of the influence of thermal up-scatter and contamination with para
      deuterium on the UCN survival time.

PMID- 12513199
TI  - Nature of low-energy dipole strength in nuclei: the case of a resonance at
      particle threshold in 208Pb.
AB  - A high-resolution (gamma,gamma') study of the electric dipole response in 208Pb
      at the S-DALINAC reveals a resonance structure centered around the neutron
      emission threshold. Microscopic quasiparticle phonon model calculations in
      realistic model spaces including the coupling to complex configurations are able
      to describe the data in great detail. The resonance is shown to result from
      surface density oscillations of the neutron skin relative to an approximately
      isospin-saturated core. It also forms an integral part of a toroidal E1 mode
      representing an example of vortex collective motion in nuclei.

PMID- 12513200
TI  - Fusion suppression and sub-barrier breakup of weakly bound nuclei.
AB  - The mechanism for the large suppression of complete fusion in the 9Be+208Pb
      reaction has been investigated through measurement of sub-barrier breakup of 9Be.
      Excluding breakup through the 8Be ground state, whose lifetime is too long, a
      prompt breakup component remains, having sufficient probability to explain the
      observed suppression of complete fusion. This appears to be associated with
      interactions at the nuclear surface. The fusion suppression is predicted to be
      almost proportional to the charge of the target nucleus, making it most
      significant in reactions with heavy nuclei.

PMID- 12513197
TI  - Coherent rho(0) production in ultraperipheral heavy-ion collisions.
AB  - The STAR Collaboration reports the first observation of exclusive rho(0)
      photoproduction, AuAu-->AuAurho(0), and rho(0) production accompanied by mutual
      nuclear Coulomb excitation, AuAu-->Au*Au*rho(0), in ultraperipheral heavy-ion
      collisions. The rho(0) have low transverse momenta, consistent with coherent
      coupling to both nuclei. The cross sections at sqrt[s(NN)]=130 GeV agree with
      theoretical predictions treating rho(0) production and Coulomb excitation as
      independent processes.

PMID- 12513201
TI  - Single-pulse phase-contrast nonlinear Raman spectroscopy.
AB  - High spectral resolution nonlinear vibrational spectroscopy with a single
      ultrashort pulse is demonstrated on a variety of samples. The spectral data are
      obtained by shaping the excitation pulse in order to control the relative phase
      between the weak resonant signal and the strong nonresonant background, in
      analogy with phase-contrast microscopy techniques. This is unlike the more
      conventional approach to nonlinear spectroscopy, in which the nonresonant
      background is reduced to a minimum. By measuring the spectrum of the coherent
      anti-Stokes Raman signal, it is possible to infer the vibrational energy levels
      in a band spanning almost an entire octave.

PMID- 12513202
TI  - Gas phase infrared spectroscopy of selectively prepared ions.
AB  - The first example of direct structural characterization of polyaromatic ions by
      coupling a Fourier transform ion cyclotron resonance mass spectrometer with an
      infrared free-electron laser is presented. Measurement of the IR spectra of
      selectively prepared ionic reactive intermediates is allowed by the association
      of the high peak power and wide tunability of the laser with the flexibility of
      the spectrometer, where several mass selection and ion reaction steps can be
      combined, as demonstrated in the case of iron cation complexes of hydrocarbons.
      The present experimental setup opens the way to understanding chemical reaction
      paths.

PMID- 12513203
TI  - Rydberg state ionization by half-cycle-pulse excitation: strong kicks create slow
      electrons.
AB  - The asymptotic velocity distribution of electrons ionized in half-cycle-pulse
      excitation of high Rydberg states (n=34), placed in a static electric field, is
      studied using electron velocity-map imaging. At weak half-cycle pulse strengths,
      the electrons escape over the saddle point in the potential. For strong half
      cycle pulses, the electrons are emitted in the direction of the field kick. The
      much slower and less intense half cycle of opposite polarity, which necessarily
      follows the main half-cycle pulse, strongly affects the momentum distribution and
      reduces the excess energy of the electrons significantly.

PMID- 12513204
TI  - Close-coupling approach to Coulomb three-body problems.
AB  - The convergent close-coupling method is shown to overcome the remaining
      discrepancies with experiment of electron-hydrogen ionization. Consequently, this
      method is able to calculate accurately the Coulomb three-body problems which
      include electron collisions with hydrogen and helium (within the frozen core
      model), and helium double photoionization at all incident energies and
      kinematical or geometrical arrangements of the outgoing electrons.

PMID- 12513205
TI  - Magnetic field control of elastic scattering in a cold gas of fermionic lithium
      atoms.
AB  - We study elastic collisions in an optically trapped spin mixture of fermionic
      lithium atoms in the presence of magnetic fields up to 1.5 kG by measuring
      evaporative loss. Our experiments confirm the expected magnetic tunability of the
      scattering length by showing the main features of elastic scattering according to
      recent calculations. We measure the zero crossing of the scattering length at
      530(3) G which is associated with a predicted Feshbach resonance at approximately
      850 G. Beyond the resonance we observe the expected large cross section in the
      triplet scattering regime.

PMID- 12513206
TI  - Nanoscale molecular superfluidity of hydrogen.
AB  - We present a microscopic quantum theoretical analysis of the nanoscale superfluid
      properties of solvating clusters of para-H2 around the linear OCS molecule. Path
      integral calculations with N=17 para-H2 molecules, constituting a full solvation
      shell, show the appearance of a significant superfluid response to rotation
      around the molecular axis at T=0.15 K. This low-temperature superfluid response
      is highly anisotropic and drops sharply as the temperature increases to T
      approximately 0.3 K. These calculations provide definitive theoretical evidence
      that an anisotropic superfluid state exists for molecular hydrogen in this
      microscopic solvation layer.

PMID- 12513207
TI  - Observation of non-phase-matched parametric amplification in resonant nonlinear
      optics.
AB  - The coupling between a resonant excitation and a nonresonant parametric process
      in a nonlinear system is studied experimentally under non-phase-matched
      conditions. Our study performed in the context of anti-Stokes stimulated Raman
      scattering provides a clear observation of the self-induced phase matching of a
      parametric process. A close agreement with theoretical predictions is observed.

PMID- 12513208
TI  - Robust propagation of two-color soliton clusters supported by competing
      nonlinearities.
AB  - We reveal numerically the remarkably robust propagation of quasistationary two
      color soliton clusters in media with competing quadratic and cubic
      nonlinearities. We predict that such clusters carrying nonzero angular momentum
      can propagate over any practically feasible crystal length before they decay,
      even in the presence of input random perturbations.

PMID- 12513209
TI  - Control of common resonances in bichromatically driven hydrogen atoms.
AB  - We report the first combined experimental-theoretical study to realize and
      control the behavior of common resonances in a periodically driven system.
      Experimental data for the ionization of H(n=51) atoms by a bichromatic (6 and 18
      GHz), linearly polarized electric field pulse show how the relative field phase
      can be used to control the ionization. 1D classical calculations show how this
      results from the phase control of the pendulumlike, common resonances, whose
      existence requires, at lowest order, two commensurate frequencies.

PMID- 12513210
TI  - Core electrostatic fluctuations and particle transport in a reversed-field pinch.
AB  - Potential and electron-density fluctuation profiles, phi(r) and n(e)(r)/n(e), are
      measured for the first time in the core of a reversed-field pinch using a heavy
      ion beam probe. It is found that the fluctuations are broadband and correlated
      with the core resonant m/n=1/6 tearing mode. The electrostatic-fluctuation
      induced particle transport in the core of standard RFP plasmas, estimated from
      measured <n(e)phi>, is small compared to the total particle flux. Measurements of
      fluctuations and estimates of fluctuation induced particle transport in improved
      confinement RFP discharges are also presented.

PMID- 12513211
TI  - Three-dimensional relativistic electromagnetic subcycle solitons.
AB  - Three-dimensional (3D) relativistic electromagnetic subcycle solitons were
      observed in 3D particle-in-cell simulations of an intense short-laser-pulse
      propagation in an underdense plasma. Their structure resembles that of an
      oscillating electric dipole with a poloidal electric field and a toroidal
      magnetic field that oscillate in phase with the electron density with frequency
      below the Langmuir frequency. On the ion time scale, the soliton undergoes a
      Coulomb explosion of its core, resulting in ion acceleration, and then evolves
      into a slowly expanding quasineutral cavity.

PMID- 12513212
TI  - Eliminating islands in high-pressure free-boundary stellarator
      magnetohydrodynamic equilibrium solutions.
AB  - Magnetic islands in free-boundary stellarator equilibria are suppressed using a
      procedure that iterates the plasma equilibrium equations and, at each iteration,
      adjusts the coil geometry to cancel resonant fields produced by the plasma. The
      coils are constrained to satisfy certain measures of engineering acceptability
      and the plasma is constrained to ensure kink stability. As the iterations
      continue, the coil geometry and the plasma simultaneously converge to an
      equilibrium in which the island content is negligible. The method is applied with
      success to a candidate plasma and coil design for the National Compact
      Stellarator Experiment [Phys. Plasmas 8, 2083 (2001)]].

PMID- 12513213
TI  - High-intensity laser-field amplification between two foils.
AB  - Interaction of two oppositely directed ultraintense laser pulses with two closely
      placed thin foils is modeled analytically and investigated by particle-in-cell
      simulation. It is shown that laser energy can be trapped and accumulated between
      the foils. The intensity could reach a 100-fold that of the pump lasers. The
      trapping is found to be bistable and the parameters for stable energy confinement
      and enhancement are given. The ultrahigh fields that can be produced have many
      potential applications, including that of verifying nonlinear quantum
      electrodynamics effects.

PMID- 12513214
TI  - Polarization of superfluid turbulence.
AB  - We show that normal-fluid eddies in turbulent helium II polarize the tangle of
      quantized vortex lines present in the flow, thus inducing superfluid vorticity
      patterns similar to the driving normal-fluid eddies. We also show that the
      polarization is effective over the entire inertial range. The results help
      explain the surprising analogies between classical and superfluid turbulence
      which have been observed recently.

PMID- 12513215
TI  - Single-particle and collective dynamics of protein hydration water: a molecular
      dynamics study.
AB  - We present an analysis based on molecular dynamics simulations of water single
      particle and collective density fluctuations in a protein crystal at 150 and 300
      K. For the collective dynamics, the calculations predict the existence of two
      sound modes. The first one around 35 meV is highly dispersive and the second one
      around 9 meV is weakly dispersive in the k range studied here (0.5<k<4.2 A(-1)).
      We provide evidence that the boson peak around 4 meV in the single particle
      spectra arises from translational motion, is present in the coherent spectra, and
      is distinct from the two sound modes.

PMID- 12513216
TI  - Formation of an icosahedral structure during the freezing of gold nanoclusters:
      surface-induced mechanism.
AB  - The freezing behavior of gold nanoclusters was studied by employing molecular
      dynamics simulations based on the semiempirical embedded-atom method.
      Investigations of the gold nanoclusters revealed that, just after freezing,
      ordered nanosurfaces with a fivefold symmetry were formed with interior atoms
      remaining in the disordered state. Further lowering of temperatures induced
      nanocrystallization of the interior atoms that proceeded from the surface towards
      the core region, finally leading to an icosahedral structure. These dynamic
      processes explain why the icosahedral cluster structure is dominantly formed in
      spite of its energetic metastability.

PMID- 12513217
TI  - Hole- and electron-vibrational couplings in oligoacene crystals: intramolecular
      contributions.
AB  - The hole-vibrational coupling is reported for anthracene, tetracene, and
      pentacene on the basis of a joint experimental and theoretical study of
      ionization spectra using high-resolution gas-phase photoelectron spectroscopy and
      first-principles correlated quantum-mechanical calculations. The hole-vibrational
      coupling is found to be significantly smaller than the electron-vibrational
      coupling in the case of these oligomers; however, both quantities are predicted
      to converge to the same value when increasing the chain length.

PMID- 12513218
TI  - Unusual sequences of tilted smectic phases in liquid crystals of bent-shape
      molecules.
AB  - The first theoretical description of the experimentally often-observed isotropic
      polar smectic phase transitions of symmetric and asymmetric bent-shape molecules
      is presented. The isotropic-tilted polar smectic phase transition requires a
      coupling among three types of ordering processes: polar packing, director tilt,
      and layer ordering. For explaining the unusual triclinic-monoclinic phase
      transition with the lower symmetry phase at higher temperature, observed in
      fluoro-containing compounds recently, a mechanism is proposed in which the layer
      ordering triggers the simultaneous onset of the tilt and polar order.

PMID- 12513219
TI  - Inverse Monte Carlo renormalization group transformations for critical phenomena.
AB  - We introduce a computationally stable inverse Monte Carlo renormalization group
      transformation method that provides a number of advantages for the calculation of
      critical properties. We are able to simulate the fixed point of a renormalization
      group for arbitrarily large lattices without critical slowing down. The log-log
      scaling plots obtained with this method show remarkable linearity, leading to
      accurate estimates for critical exponents. We illustrate this method with
      calculations in two- and three-dimensional Ising models for a variety of
      renormalization group transformations.

PMID- 12513220
TI  - Electrostatic field enhancement of Al(111) oxidation.
AB  - We show that the electrostatic charging of an aluminum oxide film by electron
      bombardment produces a greatly enhanced rate of Al(111) oxidation by O2(g) at 90
      K, compared to a film which has not been bombarded by electrons. This novel
      memory effect for prior electron irradiation is caused by the negative
      electrostatic potential created and stored on the outer oxide film surface as a
      result of electron bombardment. The high electrostatic field ( approximately
      10(7) V/cm) produced across the depth of the film is postulated to cause an
      enhancement of ion migration through the film, leading to rapid oxide film
      growth, as predicted by the Cabrera-Mott theory of low temperature metal
      oxidation.

PMID- 12513221
TI  - Structure and bonding of water on Pt(111).
AB  - We address the adsorption of water on Pt(111) using x-ray absorption, x-ray
      emission, and x-ray photoelectron spectroscopy along with calculations in the
      framework of density functional theory. Using the direct relationship between the
      electronic structure and adsorbate geometry, we show that in the first layer all
      the molecules bind directly to the surface and to each other through the in-layer
      H bonds without dissociation, creating a nearly flat overlayer. The water
      molecules are adsorbed through alternating metal-oxygen (M-O) and metal-hydrogen
      (M-HO) bonds.

PMID- 12513222
TI  - Tuning of nanotube mechanical resonances by electric field pulling.
AB  - We show here that field emission (FE) can be used to directly observe the
      vibration resonances nu(R) of carbon nanotubes (CNTs) and that the tension
      created by the applied field allows the tuning of these resonances by up to a
      factor of 10. The resonances are observable by the changes they create in the FE
      pattern or the emitted FE current. The tuning is shown to be linear in voltage
      and to follow from the basic physics of stretched strings. The method allows one
      to study the mechanical properties of individual multiwall carbon nanotubes
      within an ensemble and follow their evolution as the CNTs are modified. The
      tuning and detection should be useful for nanometric resonant devices.

PMID- 12513223
TI  - New cooperative effects in ballistic deposition of hard disks.
AB  - In this Letter, we analyze the problem of monolayer formation onto a flat surface
      by deposition of hard particles. Our detailed computer simulations of ballistic
      deposition of hard disks show significant deviations from the classical
      analytical solution obtained by J. Talbot [Phys. Rev. Lett. 68, 958 (1992)].
      These deviations are due to cooperative adsorption induced by particles trapped
      above the adsorbed layer. We show that not only the adsorption kinetics but also
      the jamming (saturation) coverage of the surface depends on the volume fraction
      of the suspension, a prediction which is completely new. These new cooperative
      effects cannot be neglected even in the case of very diluted suspensions.

PMID- 12513224
TI  - Direct imaging of the InSb001-c8 x 2 surface: evidence for large anisotropy of
      the reconstruction.
AB  - We have observed the InSb(001)-c(8 x 2) surface by using high-resolution
      transmission electron microscopy in the profile-imaging geometry. All images
      observed at temperatures up to 420 degrees C agree well with the c(8 x 2) model
      reported by Kumpf et al. [Phys. Rev. Lett. 86, 3586 (2001)]]. 1/30 sec real-time
      observations at 420 degrees C evidence that a part of the subsurface and surface
      layers (called a gull-type segment) undergo switching to and from a bulk
      configuration. The finding is suggestive of large anisotropy in the mean square
      displacement of the c(8 x 2) surface.

PMID- 12513225
TI  - Ion-beam sculpting time scales.
AB  - A study of ion sculpting dynamics in SiO2 and SiN using periodically pulsed ion
      beams reveals material transport that depends strongly on the time structure of
      the pulsed beams. It is found that significant nanoscale matter transport can
      occur over second long time scales after the ion beam has been extinguished. A
      simple phenomenological model described the dynamics of ion beam sculpting in
      terms of two material time scales. The model accounts for the surprising
      observation of enhanced matter transport affected by pulsed ion beams over
      continuous ion beam exposure.

PMID- 12513226
TI  - Universal behavior of the resistance noise across the metal-insulator transition
      in silicon inversion layers.
AB  - Studies of low-frequency resistance noise show that the glassy freezing of the
      two-dimensional (2D) electron system in the vicinity of the metal-insulator
      transition occurs in all Si inversion layers. The size of the metallic glass
      phase, which separates the 2D metal and the (glassy) insulator, depends strongly
      on disorder, becoming extremely small in high-mobility samples. The behavior of
      the second spectrum, an important fourth-order noise statistic, indicates the
      presence of long-range correlations between fluctuators in the glassy phase,
      consistent with the hierarchical picture of glassy dynamics.

PMID- 12513227
TI  - Quantum fluctuations and the closing of the Coulomb gap in a correlated
      insulator.
AB  - The "switchable mirror" yttrium hydride is one of the few strongly correlated
      systems with a continuous Mott-Hubbard metal-insulator transition. We
      systematically map out the low temperature electrical transport from deep in the
      insulator to the quantum critical point using persistent photoconductivity as a
      drive parameter. Both activated hopping over a Coulomb gap and power-law quantum
      fluctuations must be included to describe the data. Collapse of the data onto a
      universal curve within a dynamical scaling framework (with corrections) requires
      znu=6.0+/-0.5, where nu and z are the static and dynamical critical exponents,
      respectively.

PMID- 12513228
TI  - Negative spin polarization of Fe3O4 in magnetite/manganite-based junctions.
AB  - Epitaxial oxide trilayer junctions composed of magnetite (Fe3O4) and doped
      manganite (La0.7Sr0.3MnO3) exhibit inverse magnetoresistance as large as -25% in
      fields of 4 kOe. The inverse magnetoresistance confirms the theoretically
      predicted negative spin polarization of Fe3O4. Transport through the barrier can
      be understood in terms of hopping transport through localized states that
      preserve electron spin information. The junction magnetoresistance versus
      temperature curve exhibits a peak around 60 K that is explained in terms of the
      paramagnetic to ferrimagnetic transition of the CoCr2O4 barrier.

PMID- 12513229
TI  - Dynamical scaling of the quantum Hall plateau transition.
AB  - Using different experimental techniques, we examine the dynamical scaling of the
      quantum Hall plateau transition in a frequency range f=0.1-55 GHz. We present a
      scheme that allows for a simultaneous scaling analysis of these experiments and
      all other data in literature. We observe a universal scaling function with an
      exponent kappa=0.5+/-0.1, yielding a dynamical exponent z=0.9+/-0.2.

PMID- 12513230
TI  - Kondo state for a compact Cr trimer on a metallic surface.
AB  - The ground state of a Cr trimer supported on the Au(111) surface is investigated
      by means of a variational approach to the Coqblin-Schrieffer Hamiltonian. The
      temperature of Kondo-resonance formation (T(K)) for equilateral trimers increases
      drastically as compared to T(K) for a single Cr adatom. The Kondo state of a Cr
      trimer proves to be very sensitive to geometry and a small shift of any atom from
      the symmetrical position leads to a rapid decrease in T(K). These results are in
      good agreement with recent observations of the Kondo response of a single
      antiferromagnetic chromium trimer [T. Jamneala, Phys. Rev. Lett. 87, 256804
      (2001)]].

PMID- 12513231
TI  - Spin-orbit coupling, antilocalization, and parallel magnetic fields in quantum
      dots.
AB  - We investigate antilocalization due to spin-orbit coupling in ballistic GaAs
      quantum dots. Antilocalization that is prominent in large dots is suppressed in
      small dots, as anticipated theoretically. Parallel magnetic fields suppress both
      antilocalization and also, at larger fields, weak localization, consistent with
      random matrix theory results once orbital coupling of the parallel field is
      included. In situ control of spin-orbit coupling in dots is demonstrated as a
      gate-controlled crossover from weak localization to antilocalization.

PMID- 12513232
TI  - Josephson plasma resonance and phonon anomalies in trilayer Bi2Sr2Ca2Cu3O10.
AB  - The far-infrared (FIR) c axis conductivity of a Bi2223 crystal has been measured
      by ellipsometry. Below T(c) a strong absorption band develops near 500 cm(-1),
      corresponding to a transverse Josephson plasmon. The related increase in FIR
      spectral weight leads to a giant violation of the Ferrell-Glover-Tinkham sum
      rule. The gain in c axis kinetic energy accounts for a sizable part of the
      condensation energy. We also observe phonon anomalies which suggest that the
      Josephson currents lead to a drastic variation of the local electric field within
      the block of closely spaced CuO2 planes.

PMID- 12513233
TI  - Mechanical Cooper pair transportation as a source of long-distance
      superconducting phase coherence.
AB  - Transportation of Cooper pairs by a movable single Cooper-pair box placed between
      two remote superconductors is shown to establish coherent coupling between them.
      This coupling is due to entanglement of the movable box with the leads and is
      manifested in the suppression of quantum fluctuations of the relative phase of
      the order parameters of the leads. It can be probed by attaching a high
      resistance Josephson junction between the leads and measuring the current through
      this junction. The current is suppressed with increasing temperature.

PMID- 12513234
TI  - Sharp signature of a dx2-y2 quantum critical point in the Hall coefficient of
      cuprate superconductors.
AB  - We study the behavior of the Hall coefficient, R(H), in a system exhibiting
      dx(2)(-y(2)) density-wave order in a regime in which the carrier concentration,
      x, is tuned to approach a quantum critical point at which the order is destroyed.
      At the mean-field level, we find that n(Hall)=1/R(H) evinces a sharp signature of
      the transition. There is a kink in n(Hall) at the critical value of the carrier
      concentration, x(c); as the critical point is approached from the ordered side,
      the slope of n(Hall) diverges. Hall transport experiments in the cuprates, at
      high magnetic fields sufficient to destroy superconductivity, should reveal this
      effect.

PMID- 12513235
TI  - Exotic order in simple models of bosonic systems.
AB  - We show that simple Bose Hubbard models with unfrustrated hopping and short range
      two-body repulsive interactions can support stable fractionalized phases in two
      and higher dimensions, and in zero magnetic field. The simplicity of the
      constructed models advances the possibility of a controlled experimental
      realization and novel applications of such unconventional states.

PMID- 12513236
TI  - Dispersion anomalies in bilayer cuprates and the odd symmetry of the magnetic
      resonance.
AB  - We demonstrate that recent angle resolved photoemission data in bilayer cuprate
      superconductors imply that scattering of electrons between bonding and
      antibonding bands is strong compared to scattering within these bands. As a
      consequence, the resulting data can be reproduced only by a model which assumes
      that the electrons are interacting with a bosonic mode that is odd with respect
      to the layer indices. This odd symmetry is a unique property of the magnetic
      resonance observed by inelastic neutron scattering.

PMID- 12513237
TI  - Spatially resolved dynamics of localized spin-wave modes in ferromagnetic wires.
AB  - We have observed localized spin-wave modes in individual thin-film ferromagnetic
      wires using time-resolved Kerr microscopy as a micron-scale spectroscopic probe.
      The localization is due to the internal field profile present when an external
      field is applied in the plane of the film and perpendicular to the long axis of
      the wire. Spatially resolved spectra demonstrate the existence of distinct modes
      at the edges of a rectangular wire. Spectral images clearly show the crossover of
      the two edge modes into a single mode in low applied fields, in agreement with
      the results of micromagnetic simulations.

PMID- 12513238
TI  - Phase diagram of a model for diluted magnetic semiconductors beyond mean-field
      approximations.
AB  - A lattice spin-fermion model for diluted magnetic semiconductors (DMS) is
      investigated numerically, improving on previously used mean-field approximations.
      Curie temperatures are obtained varying the Mn spin x and hole n densities, and
      the impurity-hole exchange J in units of the hop-ping t. Optimal values are found
      in the subtle intermediate regime between itinerant and localized carriers. At
      intermediate and large J/t, a "clustered" state is observed above the Curie
      temperature and ferromagnetism is suppressed. Formal analogies between DMS and
      manganites are discussed.

PMID- 12513239
TI  - Permutation-symmetric multicritical points in random antiferromagnetic spin
      chains.
AB  - We present a general theory of a class of multicritical points in the phase
      diagrams of random antiferromagnetic spin chains. We show that low-energy
      properties of these points are almost completely determined by a permutation
      symmetry of the effective theory not shared by the microscopic Hamiltonian. One
      case provides an analytic theory of the quantum critical point in the random spin
      3/2 chain, studied in a recent work by Refael, Kehrein, and Fisher.

PMID- 12513240
TI  - Spin freezing and magnetic inhomogeneities in bilayer manganites.
AB  - We have performed a muon spin rotation study on polycrystalline samples of
      electron-doped layered manganites, La2-2xSr1+2xMn2O7 (0.4< or =x<1), in order to
      investigate the local magnetic structure and spin dynamics. Our results provide
      evidence for phase separation into A-type antiferromagnetic and charge-ordered
      phases for x=0.52 and spin freezing at low temperatures (T<100 K) for 0.52< or
      =x<0.75. A new phase diagram which includes this spin-freezing region is
      proposed.

PMID- 12513241
TI  - Creation of entanglement by interaction with a common heat bath.
AB  - I show that entanglement between two qubits can be generated if the two qubits
      interact with a common heat bath in thermal equilibrium, but do not interact
      directly with each other. In most situations the entanglement is created for a
      very short time after the interaction with the heat bath is switched on, but
      depending on system, coupling, and heat bath, the entanglement may persist for
      arbitrarily long times. This mechanism sheds new light on the creation of
      entanglement. A particular example of two quantum dots in a closed cavity is
      discussed, where the heat bath is given by the blackbody radiation.

PMID- 12513242
TI  - NMR implementation of a parallel search algorithm.
AB  - Recently it has been shown that the dynamics of a cluster of dipolar-coupled
      spins can be manipulated to store and process a large amount of information in a
      parallel way [Chem. Phys. Lett. 360, 161 (2002)]]. Here it is further
      demonstrated that it is possible to realize a cascade of parallel bitwise
      operations on a spin cluster so that an algorithm of parallel search can be
      experimentally implemented by means of nuclear magnetic resonance.

PMID- 12513243
TI  - Phase transitions in quantum pattern recognition.
AB  - With the help of quantum mechanics one can formulate a model of associative
      memory with optimal storage capacity. This model is generalized by introducing a
      parameter playing the role of an effective temperature. The corresponding
      thermodynamics provides criteria to tune the efficiency of quantum pattern
      recognition. It is shown that the associative memory undergoes a phase transition
      from a disordered, high-temperature phase with no correlation between input and
      output to an ordered, low-temperature phase with minimal input-output Hamming
      distance.

PMID- 12513244
TI  - Optimal scheme for estimating a pure qubit state via local measurements.
AB  - We present the optimal scheme for estimating a pure qubit state by means of local
      measurements on N identical copies. We give explicit examples for low N. For
      large N, we show that the fidelity saturates the collective measurement bound up
      to order 1/N. When the signal state lays on a meridian of the Bloch sphere, we
      show that this can be achieved without classical communication.

PMID- 12513245
TI  - Chaotic free-space laser communication over a turbulent channel.
AB  - The dynamics of errors caused by atmospheric turbulence in a self-synchronizing
      chaos-based communication system that stably transmits information over an
      approximately 5 km free-space laser link is studied experimentally. Binary
      information is transmitted using a chaotic sequence of short-term pulses as a
      carrier. The information signal slightly shifts the chaotic time position of each
      pulse depending on the information bit. We report the results of an experimental
      analysis of the atmospheric turbulence in the channel and the impact of
      turbulence on the bit-error-rate performance of this chaos-based communication
      system.

PMID- 12513246
TI  - The parts determine the whole in a generic pure quantum state.
AB  - We show that almost every pure state of multiparty quantum systems (each of whose
      local Hilbert space has the same dimension) is completely determined by the
      state's reduced density matrices of a fraction of the parties; this fraction is
      less than about two-thirds of the parties for states of large numbers of parties.
      In other words, once the reduced states of this fraction of the parties have been
      specified, there is no further freedom in the state.

PMID- 12513247
TI  - Transverse NMR relaxation as a probe of mesoscopic structure.
AB  - Transverse NMR relaxation in a macroscopic sample is shown to be extremely
      sensitive to the structure of mesoscopic magnetic susceptibility variations. Such
      a sensitivity is proposed as a novel kind of contrast in the NMR measurements.
      For suspensions of arbitrary-shaped paramagnetic objects, the transverse
      relaxation is found in the case of a small dephasing effect of an individual
      object. Strong relaxation rate dependence on the objects' shape agrees with
      experiments on whole blood. Demonstrated structure sensitivity is a generic
      effect that arises in NMR relaxation in porous media, biological systems, as well
      as in kinetics of diffusion limited reactions.

PMID- 12513248
TI  - Predictions of a spiral diffusion path for nonspherical organic molecules in
      carbon nanotubes.
AB  - The diffusive behavior of ethane and ethylene in single-walled carbon nanotubes
      is investigated using classical molecular dynamics simulations and density
      functional theory calculations. At low molecular densities, these nonspherical
      molecules follow a spiral path inside nanotubes with diameters of 13-22 A, which
      maximizes the interaction of molecular C-C bonds with the C-C bonds in the
      nanotubes. Spherical molecules, such as methane, are not predicted to follow a
      spiral diffusion path. This result quantifies the manner in which molecular shape
      and chemical bonding affects molecule-nanotube interactions and indicates the
      generality of spherical transport through nanotubes.

PMID- 12513249
TI  - Distribution of film orientations in free and strained foams.
AB  - We show that the distribution of film orientations in a free (i.e., unstrained)
      foam cluster, though in general not uniform, has the same second moments as a
      uniform distribution. This is, however, in general not true of its other moments,
      which reflects the internal order of film orientations imposed by Plateau's laws.
      For a strained cluster, we relate the deviations of the second moments of the
      orientation distribution from their values for an unstrained cluster, to the
      stresses acting on the cluster. Our predictions are corroborated by experimental
      results for free and strained two-dimensional clusters, allowing us to find the
      force on a cluster bounded by two parallel walls.

PMID- 12513250
TI  - Comment on "Lasetron: a proposed source of powerful nuclear-time-scale
      electromagnetic bursts".

PMID- 12513252
TI  - Comment on "X-ray absorption holography".

PMID- 12513254
TI  - Comment on "Coherent quasiparticle weight and its connection to high-T(c)
      superconductivity from angle-resolved photoemission".

PMID- 12513255
TI  - Comment on "Superconductivity in the two-dimensional t-J model".

PMID- 12513257
TI  - Trapping reactions with randomly moving traps: exact asymptotic results for
      compact exploration.
AB  - In a recent paper, Bray and Blythe have shown that the survival probability
      P(A)(t) of an A particle diffusing with a diffusion coefficient D(A) in a one
      dimensional system with diffusive traps B is independent of D(A) in the
      asymptotic limit t--> infinity and coincides with the survival probability of an
      immobile target in the presence of diffusive traps. Here, we show that this
      remarkable behavior has a more general range of validity and holds for systems of
      an arbitrary dimension d, integer or fractal, provided that the traps are
      "compactly exploring" the space, i.e., the "fractal" dimension d(w) of traps'
      trajectories is greater than d. For the marginal case when d(w)=d, as exemplified
      here by conventional diffusion in two-dimensional systems, the decay form is
      determined up to a numerical factor in the characteristic decay time.

PMID- 12513258
TI  - Governing equations and solutions of anomalous random walk limits.
AB  - Continuous time random walks model anomalous diffusion. Coupling allows the
      magnitude of particle jumps to depend on the waiting time between jumps.
      Governing equations for the long-time scaling limits of these models are found to
      have fractional powers of coupled space and time differential operators. Explicit
      solutions and scaling properties are presented for these equations, which can be
      used to model flow in porous media and other physical systems.

PMID- 12513259
TI  - From shear thickening to shear-induced jamming.
AB  - We show that applying shear to a suspension may lead to either thickening or
      permanent jamming, depending on the volume fraction of the considered suspension.
      Interpreting measurements of conductivity under shear, we invoke a dynamical
      structural transition to explain the origin of shear thickening in suspensions of
      non-Brownian particles. We finally suggest that shear thickening and shear
      induced jamming be regarded as two consequences of this dynamical structural
      transition.

PMID- 12513260
TI  - Osmotically driven shape-dependent colloidal separations.
AB  - The thermally induced motion of nanometer-sized surfactant micelles in water is
      used to create strong attractive forces between micron-sized disks of wax in a
      mixed aqueous dispersion of microdisks and microspheres. The short-ranged
      attractive force due to the depletion of micelles from between the microdisks is
      much stronger than that between two microspheres of similar size, and is largest
      when the disks approach face to face, so columns of microdisks form. These
      columns cream, whereas the spheres remain dispersed, providing a means for shape
      dependent colloidal separations driven by an applied micellar osmotic pressure.

PMID- 12513261
TI  - How hard is a colloidal "hard-sphere" interaction?
AB  - Poly-12-hydroxystearic acid (PHSA) is widely used as a coating on colloidal
      spheres to provide a "hard-sphere-type" interaction. These hard spheres have been
      widely used in fundamental studies of nucleation, crystallization, and glass
      formation. Most authors describe the interaction as "nearly" hard sphere. In this
      paper we directly measure this interaction, using layers of PHSA adsorbed onto
      mica sheets in a surfaces force apparatus. We find that the layers, in
      appropriate solvents, have no long-range interaction. When the solvent is
      decahydronaphthalene (decalin), the repulsion rises from zero to the maximum
      measurable over a distance range of 15-20 nm. The data is converted to equivalent
      forces between spheres of different diameters, and modeled using a hard core
      potential. Using zeroth-order perturbation theory and computer simulation, we
      demonstrate that the equation of state does not deviate from that of a perfect
      hard-sphere system under any relevant experimental conditions.

PMID- 12513262
TI  - Dynamics of the nematic phase of a bent-core liquid crystal.
AB  - The dielectric fluctuations in the uniaxial nematic phase of a bent-core liquid
      crystal have been studied by dynamic light scattering. Polarization selection of
      the scattering cross-section reveals one mode due to ordinary director
      fluctuations and, in the lower part of the nematic phase, a second mode
      attributable to fluctuations of the biaxial order parameter. The director
      fluctuations are approximately 100 times slower than observed in typical nematics
      based on straight-core molecules, suggesting that the bent core nematogenic units
      may be microscopic smectic domains ("cybotactic" clusters).

PMID- 12513263
TI  - Intercalation and buckling instability of DNA linker within locked chromatin
      fiber.
AB  - The chromatin fiber is a complex of DNA and specific proteins called histones
      forming the first structural level of organization of eukaryotic chromosomes. In
      tightly organized chromatin fibers, the short segments of naked DNA linking the
      nucleosomes are strongly end constrained. Longitudinal thermal fluctuations in
      these linkers allow intercalative mode of protein binding. We show that
      mechanical constraints generated in the first stage of the binding process induce
      linker DNA buckling; buckling in turn modifies the binding energies and
      activation barriers and creates a force of decondensation at the chromatin fiber
      level. The unique structure and properties of DNA thus yield a novel physical
      mechanism of buckling instability that might play a key role in the regulation of
      gene expression.

PMID- 12513264
TI  - Rotating unstable Langevin-type dynamics: linear and nonlinear mean passage time
      distributions.
AB  - To characterize the decay process of linear rotating unstable Langevin-type
      dynamics in the presence of constant external force, through the mean passage
      time distribution, two theoretical descriptions are proposed: one is called the
      Quasideterministic (QD) approach described in the limit of long times, and the
      other approach is formulated for not so long times. Both theories are matrix
      based and formulated in two x and y dynamical representations, y being the
      transformed space of coordinates by means of a time-dependent rotation matrix. In
      the y dynamical representation the noise as well as the external force are
      rotational. The QD approach is studied when the dynamics is not influenced by the
      external force and when it is influenced by it. In the absence of this force, the
      theory is given for n variables and leads to the same results as those obtained
      in the characterization of nonrotating unstable systems; a fact that is better
      understood in the space of coordinates y. In the presence of the external force,
      the characterization is given for two variables and it is only valid for weak
      amplitude forces. For large amplitudes, the dynamics is almost dominated by the
      deterministic rotational evolution; then the QD approach is no longer valid and
      therefore the other approach is required. The theory in this case is general and
      verified for systems of two and three variables. In the case of two variables we
      study a laser system and use the experimental data of this system to compare with
      both theoretical and simulation results. In the case of three variables, the
      theory foresees application in other fields, for instance, in plasma physics. We
      also study the time characterization of the nonlinear rotating unstable systems
      and show in general that the nonlinear correction to the linear case is a
      quantity evaluated in the deterministic limit. The same laser system studied in
      the linear case is used as a prototype model.

PMID- 12513265
TI  - Fluctuation pressure of a membrane between walls through five loops.
AB  - An earlier four-loop calculation of the fluctuation pressure of a fluid membrane
      between two infinite walls is extended to five loops. Variational perturbation
      theory is used to extract the hard-wall limit from perturbative results obtained
      with a smooth potential. Comparison with a structurally similar quantum mechanics
      problem of a particle in a box is used for an alternative way of extracting the
      membrane pressure and also to estimate the quality of the results. Our values lie
      above the best available Monte Carlo data.

PMID- 12513266
TI  - Analytical solution for the Feynman ratchet.
AB  - A search for an analytical, closed form solution of the Fokker-Planck equation
      with periodic, asymmetric potentials (ratchets) is presented. It is found that
      logarithmic-type potential functions (related to "entropic" ratchets) allow for
      an approximate solution within a certain range of parameters. An expression for
      the net current is calculated and it is shown that the efficiency of the rocked
      entropic ratchet is always low.

PMID- 12513267
TI  - Diffusion of epicenters of earthquake aftershocks, Omori's law, and generalized
      continuous-time random walk models.
AB  - The epidemic-type aftershock sequence (ETAS) model is a simple stochastic process
      modeling seismicity, based on the two best-established empirical laws, the Omori
      law (power-law decay approximately 1/t(1+theta) of seismicity after an
      earthquake) and Gutenberg-Richter law (power-law distribution of earthquake
      energies). In order to describe also the space distribution of seismicity, we use
      in addition a power-law distribution approximately 1/r(1+mu) of distances between
      triggered and triggering earthquakes. The ETAS model has been studied for the
      last two decades to model real seismicity catalogs and to obtain short-term
      probabilistic forecasts. Here, we present a mapping between the ETAS model and a
      class of CTRW (continuous time random walk) models, based on the identification
      of their corresponding master equations. This mapping allows us to use the wealth
      of results previously obtained on anomalous diffusion of CTRW. After translating
      into the relevant variable for the ETAS model, we provide a classification of the
      different regimes of diffusion of seismic activity triggered by a mainshock.
      Specifically, we derive the relation between the average distance between
      aftershocks and the mainshock as a function of the time from the mainshock and of
      the joint probability distribution of the times and locations of the aftershocks.
      The different regimes are fully characterized by the two exponents theta and mu.
      Our predictions are checked by careful numerical simulations. We stress the
      distinction between the "bare" Omori law describing the seismic rate activated
      directly by a mainshock and the "renormalized" Omori law taking into account all
      possible cascades from mainshocks to aftershocks of aftershock of aftershock, and
      so on. In particular, we predict that seismic diffusion or subdiffusion occurs
      and should be observable only when the observed Omori exponent is less than 1,
      because this signals the operation of the renormalization of the bare Omori law,
      also at the origin of seismic diffusion in the ETAS model. We present predictions
      and insights provided by the ETAS to CTRW mapping which suggest different ways
      for studying seismic catalogs. Finally, we discuss the present evidence for our
      predicted subdiffusion of seismicity triggered by a main shock, stressing the
      caveats and limitations of previous empirical works.

PMID- 12513268
TI  - Exact asymptotic results for persistence in the Sinai model with arbitrary drift.
AB  - We obtain exact asymptotic results for the disorder averaged persistence of a
      Brownian particle moving in a biased Sinai landscape. We employ a method that
      maps the problem of computing the persistence to the problem of finding the
      energy spectrum of a single-particle quantum Hamiltonian, which can be
      subsequently found. Our method allows us analytical access to arbitrary values of
      the drift (bias), thus going beyond the previous methods that provide results
      only in the limit of vanishing drift. We show that on varying the drift the
      persistence displays a variety of rich asymptotic behaviors including, in
      particular, interesting qualitative changes at some special values of the drift.

PMID- 12513269
TI  - Interplay between jamming and percolation upon random sequential adsorption of
      competing dimers and monomers.
AB  - The competitive random coadsorption of dimers and monomers, with probabilities
      P(D) and P(M), such as P(D)+P(M)=1, respectively, is studied numerically by means
      of Monte Carlo simulations. Excluded volume and nearest-neighbor infinite
      repulsion between unlike species is considered. The subtle interplay between
      competitive coadsorption, jamming behavior and the emergency of percolation
      clusters is analyzed in detail. Taking P(M) as the single parameter of the model,
      five characteristic regions where the system exhibit different physical behavior
      can be identified: I) For P(M)< or =P(M1) approximately equal to 0.4025(25) the
      standard percolation of dimers is observed; II) Within the interval
      P(M1)<P(M)<P(*)(M1) approximately equal to 0.4375(25) clusters of all species
      (monomers, dimers, and empty sites) are finite (nonpercolating); III) For
      P(*)(M1)< or =P(M)< or =P(*)(M2) approximately equal to 0.5425(25) the
      percolation of homogeneous clusters of empty sites is observed; IV) Within the
      interval P(*)(M2)<P(M)<P(M2) approximately equal to 0.5575(25), the system
      behaves as in Region II; and finally, V) For P(M2)< or =P(M), one has the
      standard percolation of monomers.

PMID- 12513270
TI  - Ground state and thermal properties of a lattice gas on a cylindrical surface.
AB  - Adsorbed gases within, or outside of, carbon nanotubes may be analyzed with an
      approximate model of adsorption on lattice sites situated on a cylindrical
      surface. Using this model, the ground state energies of alternative lattice
      structures are calculated, assuming Lennard-Jones pair interactions between the
      particles. The resulting energy and equilibrium structure are nonanalytic
      functions of radius (R) because of commensuration effects associated with the
      cylindrical geometry. Specifically, as R varies, structural transitions occur
      between configurations differing in the "ring number," defined as the number of
      atoms located at a common value of the longitudinal coordinate (z). The
      thermodynamic behavior of this system is evaluated at finite temperatures, using
      a Hamiltonian with nearest-neighbor interactions. The resulting specific heat
      bears a qualitative resemblance to that of the one-dimensional Ising model.

PMID- 12513271
TI  - Rotational dynamics of propane in Na-Y zeolite: a molecular dynamics and
      quasielastic neutron-scattering study.
AB  - We report results from molecular dynamics (MD) simulations and quasielastic
      neutron-scattering (QENS) measurements on the rotational dynamics of propane in
      Na-Y zeolite at room temperature with a loading of four molecules per alpha cage.
      Rotational part of the intermediate scattering function F(Q,t) obtained from the
      MD simulation suggests that rotational motion is faster relative to the
      translational motion. Various rotational models fitted to the MD data suggest
      that rotation is isotropic. It is found that the hydrogen atoms lie, on the
      average, on a sphere of radius 1.88+/-0.05 A, which is also the average distance
      of the hydrogen atoms from the center of mass of the propane molecule. Results
      from QENS measurements are in excellent agreement with those obtained from MD,
      suggesting that the intermolecular potential employed in the MD simulation
      provides a realistic description of propane motion within faujasite. The
      rotational diffusion constant D(R) is 1.05+/-0.09 x 10(12) sec(-1) from the QENS
      data, which may be compared with that obtained from the MD data (0.82+/-0.05 x
      10(12) sec(-1)).

PMID- 12513272
TI  - Nonunique steady states in the disordered harmonic chain.
AB  - The heat transport in disordered harmonic chains (DHCs) with arbitrary heat baths
      is studied, based on a general formulation developed by Dhar [Phys. Rev. Lett.
      86, 5882 (2001)]. The obtained temperature profile of a steady state is very
      unusual for any heat bath: (i) it is not unique, but dependent on the initial
      condition; (ii) it may be highly nonlinear, even though the temperature
      difference of the two ends of the system is in zero limit, and the temperature
      gradient inverted Delta T is not inversely proportional to the system size; and
      (iii) when a DHC is coupled to two thermostats with the same temperature, the
      temperature of the system is still not uniform. The localized higher frequency
      normal modes induced by the mass disorders are responsible for these strange
      properties.

PMID- 12513273
TI  - Structure of ternary additive hard-sphere fluid mixtures.
AB  - Monte Carlo simulations on the structural properties of ternary fluid mixtures of
      additive hard spheres are reported. The results are compared with those obtained
      from a recent analytical approximation [S. B. Yuste, A. Santos, and M. Lopez de
      Haro, J. Chem. Phys. 108, 3683 (1998)] to the radial distribution functions of
      hard-sphere mixtures and with the results derived from the solution of the
      Ornstein-Zernike integral equation with both the Martynov-Sarkisov and the Percus
      Yevick closures. Very good agreement between the results of the first two
      approaches and simulation is observed, with a noticeable improvement over the
      Percus-Yevick predictions especially near contact.

PMID- 12513274
TI  - Thermodynamics and statistical mechanics of frozen systems in inherent states.
AB  - We discuss a statistical mechanics approach in the manner of Edwards to the
      "inherent states" (defined as the stable configurations in the potential energy
      landscape) of glassy systems and granular materials. We show that at stationarity
      the inherent states are distributed according a generalized Gibbs measure
      obtained assuming the validity of the principle of maximum entropy, under
      suitable constraints. In particular, we consider three lattice models (a diluted
      spin glass, a monodisperse hard-sphere system under gravity, and a hard-sphere
      binary mixture under gravity) undergoing a schematic "tap dynamics," showing via
      Monte Carlo calculations that the time averages of macroscopic quantities over
      the tap dynamics and over such a generalized distribution coincide. We also
      discuss about the general validity of this approach to nonthermal systems.

PMID- 12513275
TI  - Velocity fluctuations in electrostatically driven granular media.
AB  - We study experimentally the particle velocity fluctuations in an
      electrostatically driven dilute granular gas. The velocity distributions have
      strong deviations from a Maxwellian form over a wide range of parameters. We have
      found that the tails of the distribution functions are consistent with a
      stretched exponential law with typical exponents of the order 3/2. Molecular
      dynamic simulations shows qualitative agreement with experimental data. Our
      results suggest that this non-Gaussian behavior is typical of most inelastic
      gases with both short- and long-range interactions.

PMID- 12513276
TI  - Statistics of the contact network in frictional and frictionless granular
      packings.
AB  - Simulated granular packings with different particle friction coefficient mu are
      examined. The distribution of the particle-particle and particle-wall normal and
      tangential contact forces P(f) are computed and compared with existing
      experimental data. Here f identical with F/(-)F is the contact force F normalized
      by the average value (-)F. P(f) exhibits exponential-like decay at large forces,
      a plateau/peak near f=1, with additional features at forces smaller than the
      average that depend on mu. Additional information beyond the one-point force
      distribution functions is provided in the form of the force-force spatial
      distribution function and the contact point radial distribution function. These
      quantities indicate that correlations between forces are only weakly dependent on
      friction and decay rapidly beyond approximately three particle diameters.
      Distributions of particle-particle contact angles show that the contact network
      is not isotropic and only weakly dependent on friction. High force-bearing
      structures, or force chains, do not play a dominant role in these three
      dimensional, unloaded packings.

PMID- 12513277
TI  - Cohesion-induced deepening transition of avalanches.
AB  - A directed avalanche model with a control parameter is introduced to describe the
      transition between cohesive and noncohesive granular material. The underlying
      dynamics of the process can be mapped to interface growth model. In that
      representation, a continuous phase transition separates the rough phase and the
      flat phase. In the avalanche formulation, this corresponds to a transition from
      deep to shallow avalanches. The scaling exponents of the avalanches indeed follow
      those of the underlying interface growth in both phases and at the transition
      point. However, the mass hyperscaling relation is broken at the transition point
      due to the fractal nature of the avalanche and a hierarchy of critical directed
      percolation processes.

PMID- 12513278
TI  - Fluctuation-dissipation relations in driven granular gases.
AB  - We study the dynamics of a two-dimensional driven inelastic gas, by means of
      direct simulation Monte Carlo techniques, i.e., under the assumption of molecular
      chaos. Under the effect of a uniform stochastic driving in the form of a white
      noise plus a friction term, the gas is kept in a nonequilibrium steady state
      characterized by fractal density correlations and non-Gaussian distributions of
      velocities; the mean-squared velocity, that is the so-called granular
      temperature, is lower than the bath temperature. We observe that a modified form
      of the Kubo relation, which relates the autocorrelation and the linear response
      for the dynamics of a system at equilibrium, still holds for the off equilibrium,
      though stationary, dynamics of the systems under investigation. Interestingly,
      the only needed modification to the equilibrium Kubo relation is the replacement
      of the equilibrium temperature with an effective temperature, which results equal
      to the global granular temperature. We present two independent numerical
      experiments, where two different observables are studied: (a) the staggered
      density current, whose response to an impulsive shear is proportional to its
      autocorrelation in the unperturbed system and (b) the response of a tracer to a
      small constant force, switched on at time t(w), which is proportional to the mean
      square displacement in the unperturbed system. Both measures confirm the validity
      of Kubo's formula, provided that the granular temperature is used as the
      proportionality factor between response and autocorrelation, at least for not too
      large inelasticities.

PMID- 12513279
TI  - Molecular dynamics simulations of crystallization of hard spheres.
AB  - We have carried out molecular dynamics simulations of the crystallization of hard
      spheres modeling colloidal systems that are studied in conventional and space
      based experiments. We use microscopic probes to investigate the effects of
      gravitational forces, polydispersity, and of bounding walls on the phase
      structure. The simulations employed an extensive exclusive particle grid method
      and the type and degree of crystalline order was studied in two independent ways:
      by the structure factor, as in experiments, and through local rotational
      invariants. We present quantitative comparisons of the nucleation rates of
      monodisperse and polydisperse hard-sphere systems and benchmark them against
      experimental results. We show how the presence of bounding walls leads to wall
      induced nucleation and rapid crystallization, and discuss the role of gravity on
      the dynamics of crystallization.

PMID- 12513280
TI  - Dynamics of an elongated magnetic droplet in a rotating field.
AB  - A model is proposed for the dynamics of an elongated droplet under the action of
      a low frequency rotating magnetic field. This model determines a set of critical
      frequencies at which the transitions to more complex bent shapes take place.
      These transitions occur through propagation of jumps of the droplet's axial
      tangent angle described by a nonlinear singularly perturbed partial differential
      equation with the intrinsic viscosity of the droplet playing the regularizing
      role.

PMID- 12513281
TI  - Heterogeneous structure in colloidal systems: the role of the microion
      disposition.
AB  - Under certain conditions colloidal systems exhibit a heterogeneous structure
      sometimes referred to as a "two state" structure, "spinodal instability," or a
      "phase separation." The present study focuses on the "orbital model" for the
      description of two geometries of colloidal clusters: a 7-particle diamond shape
      array and an 8-particle simple cubic array. The orbital model envisions the
      distribution of the microions as being dictated by the specific configuration of
      all the macroions in the system, in much the same way that electron distributions
      in molecules are determined by the array of atoms. Brownian dynamics simulations
      were performed as two similar clusters approached each other in rectangular cells
      at the volume fraction of phi(p)=0.01. The number distributions of both the
      counterion and coion species were determined three ways: the one-dimensional
      projection along the long axis of the computations cell; the three-dimensional
      number distributions in "real" space; and a "constant concentration" contour
      profile. It was found that as the two clusters approached each other the diamond
      cluster system became less stable whereas the simple cubic cluster system became
      more stable. This difference in behavior is attributed to the relative abilities
      of these structures to "share" counterions and the exclusion of the coions.

PMID- 12513282
TI  - Attractive forces in sterically stabilized colloidal suspensions: from the
      effective potential to the phase diagram.
AB  - The potential of mean force for macroparticles at infinite dilution is computed
      for several models of solvent-solvent and solvent-macroparticle interactions by
      using the reference hypernetted chain (RHNC) integral equations with Rosenfeld's
      density functional theory bridge functions. The phase diagram of the associated
      effective fluid is obtained from the RHNC free energy for the fluid branch and
      the perturbation theory for the solid one. The computation of the effective
      potential and of the fluid branch is tested by comparison with Monte Carlo
      simulation. The important modifications with respect to the pure hard spheres
      that were previously reported are confirmed. The possibility of inverting the
      relative stability of the fluid-fluid and the fluid-solid transitions by
      appropriate combination of the interaction parameters is shown. The importance of
      a fine description of the interactions is illustrated in the example of the role
      of the range of the solvent-solvent interaction potential.

PMID- 12513283
TI  - Relation between aggregation and phase separation: three-dimensional Monte Carlo
      simulations.
AB  - We study phase separation of particles in solution using Monte Carlo simulations
      of reversible aggregation on a cubic lattice. Two stages of the phase separation
      can be clearly distinguished: initial random aggregation and subsequent
      densification. Step one leads to a distribution of fractal aggregates close to
      the binodal and to a temporary gel for large attractive interaction. Step two
      leads to isolated spherical dense domains close to the binodal and branched
      wormlike strands for large attractive interactions. The transition between the
      two types of structure is gradual and there is no clear feature that shows the
      existence of a spinodal. The first stage of the phase separation is metastable
      very close to the binodal or at very large interaction energy. In the latter
      case, the second step can be viewed as an aging process of the gel formed in the
      first step.

PMID- 12513284
TI  - Three eras of micellization.
AB  - Micellization is the precipitation of lipids from aqueous solution into
      aggregates with a broad distribution of aggregation number. Three eras of
      micellization are characterized in a simple kinetic model of Becker-Doring type.
      The model assigns the same constant energy to the (k-1) monomer-monomer bonds in
      a linear chain of k particles. The number of monomers decreases sharply and many
      clusters of small size are produced during the first era. During the second era,
      nuclei are increasing steadily in size until their distribution becomes a self
      similar solution of the diffusion equation. Lastly, when the average size of the
      nuclei becomes comparable to its equilibrium value, a simple mean-field Fokker
      Planck equation describes the final era until the equilibrium distribution is
      reached.

PMID- 12513285
TI  - Depletion potential near curved surfaces.
AB  - We examine the depletion potential and force of a hard-sphere fluid on a single
      big hard sphere, located inside or outside of a hard spherical cavity, by Monte
      Carlo simulations to the hard-sphere fluid. The depletion potential is determined
      by the acceptance ratio method, while the force on the big sphere is obtained by
      two methods: numerical differentiation of the depletion potential and integration
      of the contact density of the fluid at the surface of the big sphere. The results
      are in excellent agreement with those obtained by density functional theory
      presented by Roth et al.

PMID- 12513286
TI  - Coiling instabilities of multilamellar tubes.
AB  - Myelin figures are densely packed stacks of coaxial cylindrical bilayers that are
      unstable to the formation of coils or double helices. These myelin figures appear
      to have no intrinsic chirality. We show that such cylindrical membrane stacks can
      develop an instability when they acquire a spontaneous curvature or when the
      equilibrium distance between membranes is decreased. This instability breaks the
      chiral symmetry of the stack and may result in coiling. A unilamellar cylindrical
      vesicle, on the other hand, will develop an axisymmetric instability, possibly
      related to the pearling instability.

PMID- 12513287
TI  - Dielectric-induced counterion partitioning and its effect on membrane rigidity.
AB  - We report on a nonthermal mechanism for counterion partitioning driven by
      dielectric contrasts in a charged system. This mechanism allows objects to remain
      charged even in very low dielectric mediums and at low temperatures, if a nearby
      high dielectric environment can host its counterions. This nonthermal counterion
      partitioning leads to an attractive counterion pressure that is usually much
      larger than the van der Waals forces. In the context of a lipid membrane, this
      partitioning will stiffen the membrane by approximately k(B)T.

PMID- 12513288
TI  - Nonequilibrium molecular dynamics simulation of shear-induced alignment of
      amphiphilic model systems.
AB  - We study the shear-induced alignment transition from transverse to the shear
      plane to parallel and perpendicular in a lamellar or smectics system. A recently
      proposed simple continuum model for amphiphiles is studied by large-scale
      nonequilibrium molecular dynamics simulation. We find a shear-rate dependence of
      the alignment transition under shear flow, parallel at low and perpendicular
      alignment at high shear rates. To identify the alignment and degree of order of
      these shear-induced orientations by scattering, a 3D analysis of the scattering
      data is needed.

PMID- 12513289
TI  - Probe size effects on the microrheology of associating polymer solutions.
AB  - Diffusing wave spectroscopy has been used to investigate the thermally driven
      displacement of colloidal particles dispersed in solutions of associating
      polymers (APs). The effect of varying colloidal probe size on the measured
      particle displacements is studied in particular. Recent theories of microrheology
      are examined in light of the observed effects. The associating polymer used in
      this research was a linear polyethylene oxide (PEO) chain (molecular weight 35
      000 g/mole) with a Cl14 aliphatic group appended to each end of the PEO. Above a
      critical concentration, the associating polymers display linear viscoelasticity
      consistent with the Maxwell model. The concentration of aqueous AP solutions was
      varied from 0.25 to 4.0 wt. %. At low concentration of APs, the mean square
      displacement of the colloidal beads was indistinguishable from simple Brownian
      diffusion in the aqueous solvent. However, at concentrations greater than 0.5 wt.
      %, the mean square displacement differed from simple diffusion in a way that was
      found to be consistent with the Maxwell model linear viscoelasticity (LVE) of the
      AP solutions. Significantly, for the most concentrated solutions, as the probe
      particle size was varied from 0.3 to 2.2 microm, the observed mean square
      displacement deviated substantially from the generalized Stokes-Einstein behavior
      predicted by microrheological theories. Our experiments showed that these
      deviations could not be attributed to specific physicochemical interactions at
      the probe-matrix interface, since observed mean square displacements were
      independent of different probe surface chemistries studied. Moreover, this
      particle size effect was not observed in semidilute, high molecular weight PEO
      solutions (molecular weight 4.0 x 10(6) g/mole). We concluded that possible
      effects of AP network compressibility and AP depletion at the probe surface could
      not account for the observed particle size effects. We examined recent reports of
      the structural heterogeneity in AP solutions for their possible connection to our
      observation of the breakdown of the generalized Stokes-Einstein equation for this
      system. Numerical conversion of the microscopic results to the linear
      viscoelastic moduli, G'(omega) and G"(omega), by means of a constrained
      regularization method (CONTIN), demonstrates that the experiments with larger
      probe particles are most consistent with the single-mode Maxwell model LVE
      observed by macroscopic mechanical rheology.

PMID- 12513290
TI  - Crossover between equilibrium and shear-controlled dynamics in sheared liquids.
AB  - We present a numerical simulation study of a simple monatomic Lennard-Jones
      liquid under shear flow, as a function of both temperature T and shear rate
      .gamma. By investigating different observables we find that (i) there exists a
      line, T(.gamma), in the (T-(.gamma)) plane that sharply marks the border between
      an "equilibrium" and a "shear-controlled" region for both the dynamic and the
      thermodynamic quantities; and (ii) along this line the structural relaxation
      time, tau(alpha)(T(.gamma)), is proportional to .gamma(-1), i.e., to the typical
      time scale introduced by the shear flow. Above T(.gamma), the liquid dynamics is
      unaffected by the shear flow, while below T(.gamma) both T and .gamma control the
      particle motion.

PMID- 12513291
TI  - Eutectic growth under acoustic levitation conditions.
AB  - Samples of Pb-Sn eutectic alloy with a high density of 8.5 x 10(3) kg/m(3) are
      levitated with a single-axis acoustic levitator, and containerlessly melted and
      then solidified in argon atmosphere. High undercoolings up to 38 K are obtained,
      which results in a microstructural transition of "lamellas-broken lamellas
      dendrites." This transition is further investigated in the light of the coupled
      zone for eutectic growth and the effects of ultrasound. The breaking of regular
      eutectic lamellas and suppression of gravity-induced macrosegregation of (Pb) and
      (Sn) dendrites are explained by the complicated internal flow inside the
      levitated drop, which is jointly induced by the shape oscillation, bulk vibration
      and rotation of the levitated drop. The ultrasonic field is also found to drive
      forced surface vibration, which subsequently excites capillary ripples and
      catalyzes nucleation on the sample surface.

PMID- 12513292
TI  - Surface-directed phase separation with off-critical composition: analytical and
      numerical results.
AB  - We study the interplay of wetting and phase separation in an unstable binary
      mixture (AB) with off-critical composition, placed in contact with a surface
      which prefers the component A. We consider surface potentials V(z) approximately
      z(-n), where z is the distance from the surface, and present analytical arguments
      and detailed numerical results to elucidate wetting-layer kinetics for arbitrary
      mixture compositions. If the preferred component is the minority phase, the
      wetting-layer thickness exhibits a potential-specific behavior at early times
      tau, R1 approximately tau(1/(n+2)), before crossing over to the universal growth
      law, R1 approximately tau(1/3). On the other hand, if the preferred component is
      the majority phase, there is a crossover from potential-specific growth (as
      before) to a slower growth regime.

PMID- 12513293
TI  - Parametric links among Monte Carlo, phase-field, and sharp-interface models of
      interfacial motion.
AB  - Parametric links are made among three mesoscale simulation paradigms: phase
      field, sharp-interface, and Monte Carlo. A two-dimensional, square lattice, 1/2
      Ising model is considered for the Monte Carlo method, where an exact solution for
      the interfacial free energy is known. The Monte Carlo mobility is calibrated as a
      function of temperature using Glauber kinetics. A standard asymptotic analysis
      relates the phase-field and sharp-interface parameters, and this allows the phase
      field and Monte Carlo parameters to be linked. The result is derived without bulk
      effects but is then applied to a set of simulations with the bulk driving force
      included. An error analysis identifies the domain over which the parametric
      relationships are accurate.

PMID- 12513294
TI  - Growth model with restricted surface relaxation.
AB  - We simulate a growth model with restricted surface relaxation process in d=1 and
      d=2, where d is the dimensionality of a flat substrate. In this model, each
      particle can relax on the surface to a local minimum, as the discrete surface
      relaxation model, but only within a distance s. If the local minimum is out from
      this distance, the particle evaporates through a refuse mechanism similar to the
      Kim-Kosterlitz nonlinear model. In d=1, the growth exponent beta, measured from
      the temporal behavior of roughness, indicates that in the coarse-grained limit,
      the linear term of the Kardar-Parisi-Zhang equation dominates in short times (low
      roughness) and, in asymptotic times, the nonlinear term prevails. The crossover
      between linear and nonlinear behaviors occurs in a characteristic time t(c) which
      only depends on the magnitude of the parameter s, related to the nonlinear term.
      In d=2, we find indications of a similar crossover, that is, logarithmic temporal
      behavior of roughness in short times and power law behavior in asymptotic times.

PMID- 12513295
TI  - Monolayers at the air-water interface: Maxwell displacement current and optical
      second-harmonic generation studies and theoretical treatment.
AB  - The structural properties and the surface pressure pi-A isothermal diagram have
      been investigated during compression of the 4-n-pentyl-4'-cyanobiphenyl (5CB)
      monolayer film on the water surface, both experimentally, using both the Maxwell
      displacement current (MDC) and optical second-harmonic generation (SHG)
      techniques, and theoretically, in the framework of the molecular model, assuming
      that the randomly tilted polar 5CB molecules on the water surface are replaced by
      the collective tilted array of unit vectors. The average angle is evaluated based
      on the both MDC and SHG techniques. The reasonable agreement between the
      calculated and experimental values of pi(A) was obtained.

PMID- 12513296
TI  - Dynamics of viscoelastic membranes.
AB  - We determine both the in-plane and out-of-plane dynamics of viscoelastic
      membranes separating two viscous fluids in order to understand microrheological
      studies of such membranes. We demonstrate the general viscoelastic signatures in
      the dynamics of shear, bending, and compression modes. We show that these modes
      remain independent in the presence of hydrodynamic interactions. The full
      response functions for motion both in-plane and out-of-plane are derived for the
      general case of viscoelastic films in contact with arbitrary viscous fluids.
      Specifically, we derive closed-form expressions for the in-plane longitudinal and
      transverse response functions for viscous membranes embedded in fluid media. We
      also find a screening of the otherwise two-dimensional character of the response
      to point forces due to the presence of the solvent.

PMID- 12513297
TI  - Dewetting of thin-film polymers.
AB  - In this paper we present a theoretical model for the dewetting of ultrathin
      polymer films. Assuming that the shear-thinning properties of these films can be
      described by a Cross-type constitutive equation, we analyze the front morphology
      of the dewetting film, and characterize the time evolution of the dry region
      radius, and of the rim height. Different regimes of growth are expected,
      depending on the initial film thickness, and on the power-law index involved in
      the constitutive equation. In the thin-films regime, the dry radius and the rim
      height obey power-law time dependences. We then compare our predictions with the
      experimental results obtained by Debregeas et al. [Phys. Rev. Lett. 75, 3886
      (1995)] and by Reiter [Phys. Rev. Lett. 87, 186101 (2001)].

PMID- 12513298
TI  - Eutectic colony formation: a phase-field study.
AB  - Eutectic two-phase cells, also known as eutectic colonies, are commonly observed
      during the solidification of ternary alloys when the composition is close to a
      binary eutectic valley. In analogy with the solidification cells formed in dilute
      binary alloys, colony formation is triggered by a morphological instability of a
      macroscopically planar eutectic solidification front due to the rejection by both
      solid phases of a ternary impurity that diffuses in the liquid. Here we develop a
      phase-field model of a binary eutectic with a dilute ternary impurity. We
      investigate by dynamical simulations both the initial linear regime of this
      instability, and the subsequent highly nonlinear evolution of the interface that
      leads to fully developed two-phase cells with a spacing much larger than the
      lamellar spacing. We find a good overall agreement with our recent linear
      stability analysis [M. Plapp and A. Karma, Phys. Rev. E 60, 6865 (1999)], which
      predicts a destabilization of the front by long-wavelength modes that may be
      stationary or oscillatory. A fine comparison, however, reveals that the
      assumption commonly attributed to Cahn that lamellae grow perpendicular to the
      envelope of the solidification front is weakly violated in the phase-field
      simulations. We show that, even though weak, this violation has an important
      quantitative effect on the stability properties of the eutectic front. We also
      investigate the dynamics of fully developed colonies and find that the large
      scale envelope of the composite eutectic front does not converge to a steady
      state, but exhibits cell elimination and tip-splitting events up to the largest
      times simulated.

PMID- 12513299
TI  - Dynamic and correlation properties of solid supported smectic-A films.
AB  - Dynamic properties and layer displacement-layer displacement correlation
      functions of the smectic-A films on a substrate are investigated. The
      eigenfrequencies spectrum and eigenmotions of the film are calculated within the
      framework of a discrete model. It was found that the static as well as dynamic
      properties of freely standing and solid supported smectic-A films differ
      significantly. In particular, the acoustic mode is absent in the films on a
      substrate and the surface tension is not essential for the film dynamics. The
      correlation length of the spatial layer displacement correlation functions is
      finite for films on a substrate in contrast to the free standing films. An effect
      of thermal fluctuations on the specular and diffuse x-ray scattering was
      analyzed.

PMID- 12513300
TI  - Computer simulation of polar bent-core molecules.
AB  - Results are presented from molecular dynamics simulations in the NPT ensemble of
      novel bent-core liquid crystal systems. Following on from a previous study of
      bent-core steric shape, this study examines the effect the addition of a
      transverse electric dipole has on the phase diagram of a bent-core liquid crystal
      model. A simple model of the interaction employed a two-site Gay-Berne potential
      with the sites separated by +/-0.5 reduced units with a central transverse point
      dipole, for all models investigated. The angle between the sites 180 degrees 
      gamma was varied in a range gamma=10 degrees to gamma=70 degrees suggested by
      real molecules. The addition of the dipole to the model tended to stabilize
      smectic phases and increase the angle of tilted phases. As the angle gamma
      increased, the transition temperature to the first ordered phase decreased
      markedly. Smectic A, tilted smectic B, and a spontaneously polarized smectic B
      phases were observed in the gamma=10 degrees bent-core model. The gamma=20
      degrees model showed smectic A and tilted antiferroelectric smectic B phases. The
      gamma=40 degrees model showed an antiferroelectric phase that exhibited unusual
      packing behavior. Both the gamma=20 degrees and gamma=40 degrees models
      demonstrated a significant phase biaxiality in the smectic B phases.

PMID- 12513301
TI  - Geometric approach to the Miesowicz coefficients at the region of the crystalline
      nematic transition and a universal relation for their ratio.
AB  - In this work the ratios between the Miesowicz coefficients of rigid calamitic
      nematic liquid crystals will be studied. It will be shown that the microscopic
      theory that describes these coefficients, the kinetic theory [M. Doi and S. F.
      Edwards, The Theory of Polymer Dynamics (Oxford Press, New York, 1986)], suggests
      that some ratios between the Miesowicz coefficients would have a universal
      character, that does not depend on the nematic material being examined. A set of
      experimental data has been collected from the liquid crystal literature and, once
      these data are rescaled in a common temperature scale, they point to the
      existence of such a universality. Nevertheless, only in the neighborhoods of the
      nematic-isotropic transition, do the theoretical calculations of the kinetic
      theory and the experimental data predict the same profile for this universality;
      when the region of the crystalline-nematic transition is approached theory and
      experiment present severe discrepancies. The reason for this disagreement is
      studied and it is proposed that it results from the fact that the kinetic theory
      does not take into account the packing properties of the nematic medium. A
      different approach to the calculation of these ratios is proposed and it is shown
      that it describes the experimental data for all temperatures.

PMID- 12513302
TI  - Effect of enantiomeric excess on surface structures and phase sequences in free
      standing liquid-crystal films.
AB  - We present differential optical reflectivity and null transmission ellipsometry
      data from several mixtures of MHPBC enantiomers. From this data, we have
      determined the chiral smectic phase sequence as a function of enantiomeric
      excess. The data suggest a change in the structure of the smectic-C(*)(alpha)
      phase and the surface tilt state as the enantiomeric excess is reduced. The
      results also show that the intermediate phases, smectic C(*)(FI2), smectic
      C(*)(FI1), and smectic C(*)(alpha), disappear sequentially on reducing the net
      chirality.

PMID- 12513303
TI  - Periodic deformations in nematic liquid crystals.
AB  - We reconsider the possibility of periodic deformations in nematic liquid crystal
      samples, and present a simple method to analyze their stability near the
      threshold. Our method consists in finding the matrix characterizing the total
      energy in terms of the integration constants of the linearized solutions of the
      variational problem. In the undeformed state all the integration constants are
      identically zero. Hence the analysis of the stability of the undeformed state
      reduces to the analysis of the sign of the determinants of the principal minors
      of the matrix of the quadratic form representing the total energy of the nematic
      sample. We discuss the role of the saddle-splay elastic constant and of the
      anchoring energy strength in the stability of the modulated structure. The role
      of the thickness of the sample, as well as of the polar and azimuthal anchoring
      energies, in the phenomenon is also considered.

PMID- 12513304
TI  - Dynamical coarse-graining of highly fluctuating membranes under shear flow.
AB  - The effect of strong shear flow on highly fluctuating lamellar systems stabilized
      by intermembrane collisions via the Helfrich interaction is studied. Advection
      enters the microscopic equation of motion for a single membrane via a nonlinear
      coupling. Upon coarse-graining the theory for a single bilayer up to the length
      scale of the collision length, at which a hydrodynamic description applies, an
      additional dynamical coupling is generated which is of the form of a wave-vector
      dependent tension that is nonlinear in the applied shear rate. This new term has
      consequences for the effects of strong flow on the stability and dynamics of
      lamellar surfactant phases.

PMID- 12513305
TI  - Shear-induced instabilities in layered liquids.
AB  - Motivated by the experimentally observed shear-induced destabilization and
      reorientation of smectic-A-like systems, we consider an extended formulation of
      smectic-A hydrodynamics. We include both, the smectic layering (via the layer
      displacement u and the layer normal p(circ)) and the director n(circ) of the
      underlying nematic order in our macroscopic hydrodynamic description and allow
      both directions to differ in nonequilibrium situations. In an homeotropically
      aligned sample the nematic director does couple to an applied simple shear,
      whereas the smectic layering stays unchanged. This difference leads to a finite
      (but usually small) angle between n(circ) and p(circ), which we find to be
      equivalent to an effective dilatation of the layers. This effective dilatation
      leads, above a certain threshold, to an undulation instability of the layers. We
      generalize our earlier approach [G. K. Auernhammer, H. R. Brand, and H. Pleiner,
      Rheol. Acta 39, 215 (2000)] and include the cross couplings with the velocity
      field and the order parameters for orientational and positional order and show
      how the order parameters interact with the undulation instability. We explore the
      influence of various material parameters on the instability. Comparing our
      results to recent experiments and molecular dynamic simulations, we find a good
      qualitative agreement.

PMID- 12513306
TI  - Tilt plane orientation in antiferroelectric liquid crystal cells and the origin
      of the pretransitional effect.
AB  - The optic, electro-optic, and dielectric properties of antiferroelectric liquid
      crystals (AFLCs) are analyzed and discussed in terms of the local tilt plane
      orientation. We show that the so-called pretransitional effect is a combination
      of two different electro-optic modes: the field-induced antiphase distortion of
      the antiferroelectric structure and the field-induced reorientation of the tilt
      plane. In the presence of a helix, the latter corresponds to a field-induced
      distortion of the helix. Both electro-optic modes are active only when the
      electric field has a component along the tilt plane. Thus, by assuring a
      horizontal surface-stabilized condition, where the helix is unwound by surface
      action and the tilt plane is everywhere parallel to the cell plates, the
      pretransitional effect should be suppressed. We also discuss the dielectrically
      active modes in AFLCs and under which circumstances they contribute to the
      measured dielectric permittivity.

PMID- 12513307
TI  - Liquid-crystal-solid interface structure at the antiferroelectric-ferroelectric
      phase transition.
AB  - Total internal reflection is used to probe the molecular organization at the
      surface of a tilted chiral smectic liquid crystal at temperatures in the vicinity
      of the bulk antiferroelectric-ferroelectric phase transition. Data are
      interpreted using an exact analytical solution of a real model for ferroelectric
      order at the surface. In the mixture T3, ferroelectric surface order is expelled
      with the bulk ferroelectric-antiferroelectric transition. The conditions for
      ferroelectric order at the surface of an antiferroelectric bulk are presented.

PMID- 12513308
TI  - Semisoft elasticity and director reorientation in stretched sheets of nematic
      elastomers.
AB  - A two-dimensional effective model for the semisoft elastic behavior of nematic
      elastomers is derived in the thin film limit. The model is used to investigate
      numerically the force-stretch curves and the deformed shape, and to resolve the
      local patterns in the director orientation in a stretching experiment. From the
      force-stretch curves we recover the two critical stretches which mark the
      transition from hard to soft and back to hard response. We present an analytical
      model for their dependence on the aspect ratio of the sample, and compare it with
      numerical results.

PMID- 12513309
TI  - Reversible negative thermal expansion of polymer films.
AB  - A basic understanding of the properties of thin polymer films is of fundamental
      importance for developing applications in nanotechnology. Results of energy and
      angle dispersive x-ray reflectivity measurements on polymer thin films as a
      function of temperature exhibit reversible negative thermal expansion below the
      glass transition temperature T(g). Above T(g), the thickness expansion becomes
      almost equal to the expected bulk volume expansion. These results could be
      explained on the basis of evolution of disorder with temperature at the
      interfaces, chain entanglement and associated entropy changes.

PMID- 12513310
TI  - Semiflexible polymer in the cactus approximation.
AB  - We investigate a cactus approximation for the analysis of a lattice polymer model
      (self-avoiding walk) in two and three dimensions. We focus on the semiflexible
      model, which incorporates both an attractive short range interaction between
      monomers that are nonconsecutive along the chain, and a bending energy
      (stiffness). In agreement with Monte Carlo simulations, we find two different
      qualitative behaviors. In the low stiffness regime the polymer undergoes two
      different transitions upon decreasing temperature: an ordinary Theta collapse
      from a swollen ("coil") state to a disordered compact ("globule") state, and then
      a first-order transition to an orientationally ordered ("anisotropic") state. In
      the high stiffness regime the system displays a single first-order collapse from
      the coil state at high temperature to the anisotropic state at low temperature.
      We show that the cactus approximation is able to recover even fine qualitative
      features of the phase diagram, such as the stiffness dependence of the Theta
      temperature, with a relatively small computational effort.

PMID- 12513311
TI  - Shear-induced shift of spinodal line in entangled polymer blends.
AB  - We study the shear-flow effects on phase separation of entangled polymer blends
      by incorporating into the chemical potential a nonequilibrium contribution due to
      the flow. The results are compared with those of a previous analysis by other
      authors which did not modify the chemical potential but used a different
      assumption for the stress tensor of the blend.

PMID- 12513312
TI  - Statistical model for receptor-ligand binding thermodynamics.
AB  - We present a simple statistical model to describe receptor-ligand binding in
      terms of the number of binding contact residues and the number of separate
      binding regions as a function of the temperature. The fact that the binding
      depends on various random factors is modeled by a distribution of local binding
      energies and we take into account that the interaction between receptor and
      ligand is only of significance for the activation of the receptor if the total
      binding energy exceeds a threshold energy. We interpret our results in the light
      of both experimentally observed antibody-antigen binding configurations and
      theoretical studies in the zero-temperature limit.

PMID- 12513313
TI  - Stages of spike time variability during neuronal responses to transient inputs.
AB  - In cerebral cortex, cells tend to fire in response to strong transient
      fluctuations in input, produced by synchronous population activity, which reset
      the precision of firing and erase correlations between prior and future spike
      times. Here, using experiments and modeling, we study the accumulation of spike
      time variance in response to single decaying transient stimuli. All such
      responses go through distinct stages in time. When the stimulus is high, variance
      is held low, while at low stimulus levels near threshold, variance rises
      dramatically, approaching a Poisson level. This behavior was reproduced in a
      stochastically simulated Hodgkin-Huxley model, and in two simpler models, class 1
      (Morris-Lecar) and class 2 (FitzHugh-Nagumo), incorporating Ornstein-Uhlenbeck
      noise. Early stage variance represents perturbation of uniform limit-cycle motion
      of the dynamical variables. Late stage variance reflects random motion of the
      dynamical variables captured within the basin of the resting fixed point. We show
      that the two stages have different sensitivities to the amplitude and time scale
      of noise, and relate this to coherence resonance. This rapid breakdown in
      reliability during responses to transient stimuli may restrict precise signalling
      by spike times to brief time windows, and limit the duration of coherent
      synchronous responses in the cortex.

PMID- 12513314
TI  - Termination of reentry in an inhomogeneous ring of model cardiac cells.
AB  - Reentrant waves propagating in a ring or annulus of excitable media are a model
      of the basic mechanism underlying a major class of irregular cardiac rhythms
      known as anatomical reentry. Such reentrant waves are terminated by rapid
      electrical stimulation (pacing) from an implantable device. Because the
      mechanisms of such termination are poorly understood, we study pacing of
      anatomical reentry in a one-dimensional ring of model cardiac cells. For
      realistic off-circuit pacing, our model-independent results suggest that circuit
      inhomogeneities, and the electrophysiological dynamical changes they introduce,
      may be essential for terminating reentry in some cases.

PMID- 12513315
TI  - Estimating the strength of bone using linear response.
AB  - Accurate diagnostic tools are required for effective management of osteoporosis;
      one method to identify additional diagnostics is to search for observable
      consequences of bone loss. An analysis of a model system is used to show that
      weakening of a bone is accompanied by a reduction of the fraction of the bone
      that participates in load transmission. On the basis of this observation, it is
      argued that the ratio Gamma of linear responses of a network to dc and high
      frequency ac driving can be used as a surrogate for their strength. Protocols
      needed to obtain Gamma for bone samples are discussed.

PMID- 12513316
TI  - Wave-number spectrum of electroencephalographic signals.
AB  - A recently developed, physiologically based continuum model of corticothalamic
      electrodynamics is used to derive the theoretical form of the
      electroencephalographic wave-number spectrum and its projection onto a one
      dimensional recording array. The projected spectrum is found to consist of a
      plateau followed by regions of power-law decrease with various exponents, which
      are dependent on both model parameters and temporal frequency. The theoretical
      spectrum is compared with experimental results obtained in other studies, showing
      good agreement. The model provides a framework for understanding the nature of
      the spatial power spectrum by linking the underlying physiology with the large
      scale dynamics of the brain.

PMID- 12513317
TI  - Multifractal analysis of DNA walks and trails.
AB  - The characterization of the long-range order and fractal properties of DNA
      sequences has proved a difficult though rewarding task mainly due to the mosaic
      character of DNA consisting of many interwoven patches of various lengths with
      different nucleotide constitutions. We apply here a recently proposed
      generalization of the detrended fluctuation analysis method to show that the DNA
      walk construction, in which the DNA sequence is viewed as a time series, exhibits
      a monofractal structure regardless of the existence of local trends in the
      series. In addition, we point out that the monofractal structure of the DNA walks
      carries over to an apparently alternative graphical construction given by the
      projection of the DNA walk into the d spatial coordinates, termed DNA trails. In
      particular, we calculate the fractal dimension D(t) of the DNA trails using a
      well-known result of fractal theory linking D(t) to the Hurst exponent H of the
      corresponding DNA walk. Comparison with estimates obtained by the standard box
      counting method allows the evaluation of both finite-length and local trends
      effects.

PMID- 12513318
TI  - Stiffening of fluid membranes due to thermal undulations: density-matrix
      renormalization-group study.
AB  - It has been considered that the effective bending rigidity of fluid membranes
      should be reduced by thermal undulations. However, recent thorough investigation
      by Pinnow and Helfrich revealed the significance of measure factors for the
      partition sum. Accepting the local curvature as a statistical measure, they found
      that fluid membranes are stiffened macroscopically. In order to examine this
      remarkable idea, we performed extensive ab initio simulations for a fluid
      membrane. We set up a transfer matrix that is diagonalized by means of the
      density-matrix renormalization group. Our method has an advantage, in that it
      allows us to survey various statistical measures. As a consequence, we found that
      the effective bending rigidity flows toward strong coupling under the choice of
      local curvature as a statistical measure. On the contrary, for other measures
      such as normal displacement and tilt angle, we found a clear tendency toward
      softening.

PMID- 12513319
TI  - Systematic derivation of reaction-diffusion equations with distributed delays and
      relations to fractional reaction-diffusion equations and hyperbolic transport
      equations: application to the theory of Neolithic transition.
AB  - We introduce a general method for the systematic derivation of nonlinear reaction
      diffusion equations with distributed delays. We study the interactions among
      different types of moving individuals (atoms, molecules, quasiparticles,
      biological organisms, etc). The motion of each species is described by the
      continuous time random walk theory, analyzed in the literature for transport
      problems, whereas the interactions among the species are described by a set of
      transformation rates, which are nonlinear functions of the local concentrations
      of the different types of individuals. We use the time interval between two jumps
      (the transition time) as an additional state variable and obtain a set of
      evolution equations, which are local in time. In order to make a connection with
      the transport models used in the literature, we make transformations which
      eliminate the transition time and derive a set of nonlocal equations which are
      nonlinear generalizations of the so-called generalized master equations. The
      method leads under different specified conditions to various types of nonlocal
      transport equations including a nonlinear generalization of fractional diffusion
      equations, hyperbolic reaction-diffusion equations, and delay-differential
      reaction-diffusion equations. Thus in the analysis of a given problem we can fit
      to the data the type of reaction-diffusion equation and the corresponding
      physical and kinetic parameters. The method is illustrated, as a test case, by
      the study of the neolithic transition. We introduce a set of assumptions which
      makes it possible to describe the transition from hunting and gathering to
      agriculture economics by a differential delay reaction-diffusion equation for the
      population density. We derive a delay evolution equation for the rate of advance
      of agriculture, which illustrates an application of our analysis.

PMID- 12513320
TI  - Bimodal oscillations in nephron autoregulation.
AB  - The individual functional unit of the kidney (the nephron) displays oscillations
      in its pressure and flow regulation at two different time scales: fast
      oscillations associated with a myogenic dynamics of the afferent arteriole, and
      slower oscillations arising from a delay in the tubuloglomerular feedback. We
      investigate the intra- and internephron entrainment of the two time scales. In
      addition to full synchronization, both wavelet analyses of experimental data and
      numerical simulations reveal a partial entrainment in which neighboring nephrons
      attain a state of chaotic synchronization with respect to their slow dynamics,
      but the fast dynamics remain desynchronized.

PMID- 12513321
TI  - Storage capacity of attractor neural networks with depressing synapses.
AB  - We compute the capacity of a binary neural network with dynamic depressing
      synapses to store and retrieve an infinite number of patterns. We use a
      biologically motivated model of synaptic depression and a standard mean-field
      approach. We find that at T=0 the critical storage capacity decreases with the
      degree of the depression. We confirm the validity of our main mean-field results
      with numerical simulations.

PMID- 12513322
TI  - Design of lattice proteins with explicit solvent.
AB  - Protein design is important to develop new drugs. As such, a knowledge of the
      correct model to use to design novel proteins is of the utmost importance. Here
      we show that a simple model where the solvent degrees of freedom are
      (semi)explicitly taken into account performs better than other existing models
      when compared to real data. Some consequences on the criteria to be used for
      protein design are discussed.

PMID- 12513323
TI  - Model of elastic responses of single DNA molecules in collapsing transition.
AB  - We present a simple phenomenological model to describe elastic responses of a
      collapsed single DNA molecule. The model is represented by the elastic theory for
      the wormlike chain combined with the order-parameter equation, which accounts for
      the intramolecular transition kinetics. Our continuum and discrete model
      reproduces the force plateaus and the stick-release patterns in the force
      extension curves, respectively. Both of the elastic responses have been observed
      experimentally by changing the concentration of the condensing agents.

PMID- 12513324
TI  - Surface relaxation in protein crystals.
AB  - Surface x-ray diffraction measurements were performed on (111) growth faces of
      crystals of the cellular iron-storage protein, horse spleen ferritin. Crystal
      truncation rods (CTR) were measured. A fit of the measured profile of the CTR
      revealed a surface roughness of 48+/-4.5 A and a top layer spacing contraction of
      3.9+/-1.5%. In addition to the peak from the CTR, the rocking curves of the
      crystals displayed unexpected extra peaks. Multiple scattering is demonstrated to
      account for them. Future applications of the method could allow the exploration
      of hydration effects on the growth of protein crystals.

PMID- 12513325
TI  - Dynamic phase separation of fluid membranes with rigid inclusions.
AB  - Membrane shape fluctuations induce attractive interactions between rigid
      inclusions. Previous analytical studies showed that the fluctuation-induced pair
      interactions are rather small compared to thermal energies, but also that
      multibody interactions cannot be neglected. In this paper, it is shown
      numerically that shape fluctuations indeed lead to the dynamic separation of the
      membrane into phases with different inclusion concentrations. The tendency of
      lateral phase separation strongly increases with the inclusion size. Large
      inclusions aggregate at very small inclusion concentrations and for relatively
      small values of the inclusions' elastic modulus.

PMID- 12513326
TI  - Analytical solution for steady-state populations in the self-assembly of
      microtubules from nucleating sites.
AB  - In addition to the biological importance of microtubules, which form a portion of
      the cellular cytoskeleton and a network for intracellular transport, the kinetics
      of microtubule self-assembly have generated great interest because individual
      microtubules exist in growing and decaying phases, with randomly occurring
      interconversions between them. Although a great deal is known concerning the
      microscopic details of these growth and decay processes, no description is
      available for the steady-state microtubule concentrations that are observed
      experimentally when microtubules are grown from nucleating sites. We generalize
      Hill's two-state model to include the dependence of the rates on tubulin
      concentration for systems where microtubules are grown from nucleating sites. An
      analytic solution is provided here to the resulting nonlinear, doubly infinite
      set of kinetic equations for the steady-state concentrations of both the growing
      and decaying phase microtubules as a function of the degree n of self-assembly
      and of the tubulin concentration. We also discuss the conditions for the
      stability of the steady state.

PMID- 12513327
TI  - Kinetics of the catalysis-driven aggregation processes.
AB  - We study a catalysis-driven aggregation model in which irreversible growth of A
      aggregates occurs only with the help of the catalyst. The results show that
      kinetics of the system depends strongly on whether the catalyst coagulates by
      itself or not. The mass distribution of A clusters obeys a conventional scaling
      law in the case without self-coagulation of the catalyst, while for the reverse
      case the evolution of the system falls in a peculiar scaling regime. Our theory
      applies to diverse phenomena such as the cluster-size distribution in a chemical
      system.

PMID- 12513328
TI  - Exponential velocity tails in a driven inelastic Maxwell model.
AB  - The problem of the steady-state velocity distribution in a driven inelastic
      Maxwell model of shaken granular material is revisited. Numerical solution of the
      master equation and analytical arguments show that the model has bilateral
      exponential velocity tails [P(v) approximately e(-|v|/sqrt[D])], where D is the
      amplitude of the noise. Previous study of this model predicted Gaussian tails
      [P(v) approximately e(-av(2))].

PMID- 12513329
TI  - Reaction-diffusion wave fronts: multigeneration biological species under climate
      change.
AB  - A generalization of reaction-diffusion models to multigeneration biological
      species is presented. It is based on more complex random walks than those in
      previous approaches. The new model is developed analytically up to infinite
      order. Our predictions for the speed agree to experimental data for several
      butterfly species better than existing models. The predicted dependence for the
      speed on the number of generations per year allows us to explain the change in
      speed observed for a specific invasion.

PMID- 12513330
TI  - Correlation differences in heartbeat fluctuations during rest and exercise.
AB  - We study the heartbeat activity of healthy individuals at rest and during
      exercise. We focus on correlation properties of the intervals formed by
      successive peaks in the pulse wave and find significant scaling differences
      between rest and exercise. For exercise the interval series is anticorrelated at
      short-time scales and correlated at intermediate-time scales, while for rest we
      observe the opposite crossover pattern--from strong correlations in the short
      time regime to weaker correlations at larger scales. We also suggest a
      physiologically motivated stochastic scenario to provide an intuitive explanation
      of the scaling differences between rest and exercise.

PMID- 12513331
TI  - Evolutionary prisoner's dilemma games with voluntary participation.
AB  - Voluntary participation in public good games has recently been demonstrated to be
      a simple yet effective mechanism to avoid deadlocks in states of mutual defection
      and to promote persistent cooperative behavior. Apart from cooperators and
      defectors a third strategical type is considered: the risk averse loners who are
      unwilling to participate in the social enterprise and rather rely on small but
      fixed earnings. This results in a rock-scissors-paper type of cyclic dominance of
      the three strategies. In the prisoner's dilemma, the effects of voluntary
      participation crucially depend on the underlying population structure. While
      leading to homogeneous states of all loners in well-mixed populations, we
      demonstrate that cyclic dominance produces self-organizing patterns on square
      lattices but leads to different types of oscillatory behavior on random regular
      graphs: the temptation to defect determines whether damped, periodic, or
      increasing oscillations occur. These Monte Carlo simulations are complemented by
      predictions from pair approximation reproducing the results for random regular
      graphs particularly well.

PMID- 12513332
TI  - Error threshold transition in the random-energy model.
AB  - We perform a statistical analysis of the error threshold transition in
      quasispecies evolution on a random-energy fitness landscape. We obtain a precise
      description of the genealogical properties of the population through extensive
      numerical simulations. We find a clear phase transition and can distinguish two
      regimes of evolution: The first, for low mutation rates, is characterized by
      strong selection, and the second, for high mutation rates, is characterized by
      quasineutral evolution.

PMID- 12513333
TI  - Resealing dynamics of a cell membrane after electroporation.
AB  - The membrane of a living cell consists of a bilayer of amphipolar lipid molecules
      as well as much larger proteins. Transmembrane potentials of up to 120 mV are
      physiologic and well tolerated, but when the potential is more than 300 mV, this
      lipid bilayer is unstable. Pores are then formed through which measurable flow of
      ions can occur. We follow currents through frog muscle cell membranes under 4-ms
      pulses of up to 440 mV. We present a theory that allows us to describe the
      relaxation of the current back to zero after the pulse in terms of membrane
      parameters. We obtain a line tension of 3.6 x 10(-6) N, which is similar to that
      found in artificial lipid bilayers.

PMID- 12513334
TI  - Metastability and weak mixing in classical long-range many-rotator systems.
AB  - We perform a molecular dynamical study of the isolated d=1 classical Hamiltonian
      H=1 / 2 summation operator (N)(i=1)L(2)(i)+ summation operator (i not equal j)[1
      cos(theta(i)-theta(j))]/r(alpha)(ij); (alpha> or =0), known to exhibit a second
      order phase transition, being disordered for u identical with U/NN> or
      =u(c)(alpha,d) and ordered otherwise [U identical with total energy and N
      identical with (N(1-alpha/d)-alpha/d)/(1-alpha/d)]. We focus on the nonextensive
      case alpha/d< or =1 and observe that, for u<u(c), a basin of attraction exists
      for the initial conditions for which the system quickly relaxes onto a long
      standing metastable state (whose duration presumably diverges with N-like square
      root[N]) which eventually crosses over to the microcanonical Boltzmann-Gibbs
      stable state. It is exhibited that the appropriately scaled maximal Lyapunov
      exponent lambda(max)(u<u(c))(metastable) proportional, variant N(
      kappa(metastable));(N--> infinity ), where, for all values of alpha/d,
      kappa(metastable) numerically coincides with one third of its value for u>u(c),
      hence decreases from 1/9 to zero when alpha/d increases from zero to unity,
      remaining zero thereafter. This simple connection between anomalies above and
      below the critical point reinforces the nonextensive universality scenario.

PMID- 12513335
TI  - Cascade-based attacks on complex networks.
AB  - We live in a modern world supported by large, complex networks. Examples range
      from financial markets to communication and transportation systems. In many
      realistic situations the flow of physical quantities in the network, as
      characterized by the loads on nodes, is important. We show that for such networks
      where loads can redistribute among the nodes, intentional attacks can lead to a
      cascade of overload failures, which can in turn cause the entire or a substantial
      part of the network to collapse. This is relevant for real-world networks that
      possess a highly heterogeneous distribution of loads, such as the Internet and
      power grids. We demonstrate that the heterogeneity of these networks makes them
      particularly vulnerable to attacks in that a large-scale cascade may be triggered
      by disabling a single key node. This brings obvious concerns on the security of
      such systems.

PMID- 12513336
TI  - Range-based attack on links in scale-free networks: are long-range links
      responsible for the small-world phenomenon?
AB  - The small-world phenomenon in complex networks has been identified as being due
      to the presence of long-range links, i.e., links connecting nodes that would
      otherwise be separated by a long node-to-node distance. We find, surprisingly,
      that many scale-free networks are more sensitive to attacks on short-range than
      on long-range links. This result, besides its importance concerning network
      efficiency and/or security, has the striking implication that the small-world
      property of scale-free networks is mainly due to short-range links.

PMID- 12513337
TI  - Irreversible quantum baker map.
AB  - We propose a generalization of the model of classical baker map on the torus, in
      which the images of two parts of the phase space do overlap. This transformation
      is irreversible and cannot be quantized by means of a unitary Floquet operator. A
      corresponding quantum system is constructed as a completely positive map acting
      in the space of density matrices. We investigate spectral properties of this
      superoperator and their link with the increase of the entropy of initially pure
      states.

PMID- 12513338
TI  - Chaos-based secure communications in a large community.
AB  - One-way coupled map lattices are used for cryptography in secure communication,
      based on spatiotemporal chaos synchronization. The sensitivity of synchronization
      between the encryption and decryption systems can be adjusted by varying the
      system size. With a suitable parameter combination, the cryptosystem can reach
      optimal trade-off of security and performance, i.e., it shows high security
      (resistant against the public-structure and known-plaintext attacks) together
      with fast encryption (and decryption) speed. An experiment of duplex voice
      transmission through university network is realized, which confirms the above
      advantages of our approach.

PMID- 12513339
TI  - Spectral theory for the failure of linear control in a nonlinear stochastic
      system.
AB  - We consider the failure of localized control in a nonlinear spatially extended
      system caused by extremely small amounts of noise. It is shown that this failure
      occurs as a result of a nonlinear instability. Nonlinear instabilities can occur
      in systems described by linearly stable but strongly non-normal evolution
      operators. In spatially extended systems the non-normality manifests itself in
      two different but complementary ways: transient amplification and spectral
      focusing of disturbances. We show that temporal and spatial aspects of the non
      normality and the type of nonlinearity are all crucially important to understand
      and describe the mechanism of nonlinear instability. Presented results are
      expected to apply equally to other physical systems where strong non-normality is
      due to the presence of mean flow rather than the action of control.

PMID- 12513340
TI  - Vibrational modes in plasma crystals due to nonlinear temperature distribution in
      gas discharge plasmas.
AB  - It is shown that a nonlinear temperature distribution in gas discharge plasma
      leads to a specific low-frequency mode of a quasi-two-dimensional plasma crystal.
      Linear dispersion characteristics of the mode are obtained. The characteristics
      of the mode can depend strongly on the temperature gradients and therefore can be
      effectively controlled by the experimental conditions.

PMID- 12513341
TI  - Two-loop critical fluctuation-dissipation ratio for the relaxational dynamics of
      the O(N) Landau-Ginzburg Hamiltonian.
AB  - The off-equilibrium purely dissipative dynamics (model A) of the O(N) vector
      model is considered at criticality in an epsilon=4-d>0 expansion up to
      O(epsilon(2)). The scaling behavior of two-time response and correlation
      functions at zero momentum, the associated universal scaling functions and the
      nontrivial limit of the fluctuation-dissipation ratio are determined in the aging
      regime.

PMID- 12513342
TI  - Secure key-exchange protocol with an absence of injective functions.
AB  - The security of neural cryptography is investigated. A key-exchange protocol over
      a public channel is studied where the parties exchanging secret messages use
      multilayer neural networks which are trained by their mutual output bits and
      synchronize to a time dependent secret key. The weights of the networks have
      integer values between +/-L. Recently an algorithm for an eavesdropper which
      could break the key was introduced by [A. Shamir, A. Mityagin, and A. Klimov,
      Ramp Session (Eurocrypt, Amsterdam, 2002)]. We show that the synchronization time
      increases with L2 while the probability to find a successful attacker decreases
      exponentially with L. Hence for large L we find a secure key-exchange protocol
      which depends neither on number theory nor on injective trapdoor functions used
      in conventional cryptography.

PMID- 12513343
TI  - Hysteresis phenomena in CO catalytic oxidation system in the presence of
      inhomogeneities of the catalyst surface.
AB  - The hysteresis phenomena in the CO catalytic oxidation system are studied by
      Monte Carlo simulation in the presence of the inhomogeneities of the catalyst
      surface. We show that the O-passivated state is destroyed due to the
      inhomogeneities of the surface, in contrast to the classical Ziff-Gulari-Barshad
      model. The defects on the surface have a significant effect on the hysteresis
      transition points. Most importantly, the supercritical nucleation and growth of
      the O adatom island during the transition from a low reactivity to a high
      reactivity states are closely related to the inhomogeneities of the catalyst
      surface. It is shown that the width of the hysteresis loop shrinks as the scan
      rate beta(CO) of y(CO) (the fraction of CO in gas phase) decreases, but there
      exists a finite width of the hysteresis loop even if beta(CO) becomes infinitely
      small. On the other hand, the width of the hysteresis loop decreases with
      decreasing the diffusion rate, and even the hysteresis loop may disappear for a
      slow diffusion. These simulation results are in good consistency with the
      previous relevant experimental results.

PMID- 12513344
TI  - Variational formulation of nonequilibrium thermodynamics for hydrodynamic pattern
      formations.
AB  - It is shown that a direct extension of the variational principle of near
      equilibrium states due to Onsager leads to the analogous principle in
      hydrodynamic flows; the entropy production rate of an isolated system is
      maximized both near and far from equilibrium. It possesses as its extremal paths
      the solutions to the hydrodynamic equation of motion, and provides a general
      pattern selection criterion far from equilibrium.

PMID- 12513345
TI  - First-order transition of tethered membranes in three-dimensional space.
AB  - We study a model of phantom tethered membranes, embedded in three-dimensional
      space, by extensive Monte Carlo simulations. The membranes have hexagonal lattice
      structure where each monomer is interacting with six nearest-neighbors (NN).
      Tethering interaction between NN, as well as curvature penalty between NN
      triangles are taken into account. This model is new in the sense that NN
      interactions are taken into account by a truncated Lennard-Jones potential
      including both repulsive and attractive parts. The main result of our study is
      that the system undergoes a first-order crumpling transition from low-temperature
      flat phase to high-temperature crumpled phase, in contrast with early numerical
      results on models of tethered membranes.

PMID- 12513346
TI  - Nondeterministic density classification with diffusive probabilistic cellular
      automata.
AB  - We present a probabilistic cellular automaton (CA) with two absorbing states
      which performs classification of binary strings in a nondeterministic sense. In a
      system evolving under this CA rule, empty sites become occupied with a
      probability proportional to the number of occupied sites in the neighborhood,
      while occupied sites become empty with a probability proportional to the number
      of empty sites in the neighborhood. The probability that all sites become
      eventually occupied is equal to the density of occupied sites in the initial
      string.

PMID- 12513347
TI  - Oscillations and dynamics in a two-dimensional prey-predator system.
AB  - Using Monte Carlo simulations we study two-dimensional prey-predator systems.
      Measuring the variance of densities of prey and predators on the triangular
      lattice and on the lattice with eight neighbors, we conclude that temporal
      oscillations of these densities vanish in the thermodynamic limit. This result
      suggests that such oscillations do not exist in two-dimensional models, at least
      when driven by local dynamics. Depending on the control parameter, the model
      could be either in an active or in an absorbing phase, which are separated by the
      critical point. The critical behavior of this model is studied using the
      dynamical Monte Carlo method. This model has two dynamically nonsymmetric
      absorbing states. In principle both absorbing states can be used for the analysis
      of the critical point. However, dynamical simulations which start from the
      unstable absorbing state suffer from metastablelike effects, which sometimes
      renders the method inefficient.

PMID- 12513348
TI  - Theory of domain patterns in systems with long-range interactions of Coulomb
      type.
AB  - We develop a theory of the domain patterns in systems with competing short-range
      attractive interactions and long-range repulsive Coulomb interactions. We take an
      energetic approach, in which patterns are considered as critical points of a mean
      field free energy functional. Close to the microphase separation transition, this
      functional takes on a universal form, allowing us to treat a number of diverse
      physical situations within a unified framework. We use asymptotic analysis to
      study domain patterns with sharp interfaces. We derive an interfacial
      representation of the pattern's free energy which remains valid in the
      fluctuating system, with a suitable renormalization of the Coulomb interaction's
      coupling constant. We also derive integro-differential equations describing
      stationary domain patterns of arbitrary shapes and their thermodynamic stability,
      coming from the first and second variations of the interfacial free energy. We
      show that the length scale of a stable domain pattern must obey a certain scaling
      law with the strength of the Coulomb interaction. We analyzed the existence and
      stability of localized (spots, stripes, annuli) and periodic (lamellar,
      hexagonal) patterns in two dimensions. We show that these patterns are metastable
      in certain ranges of the parameters and that they can undergo morphological
      instabilities leading to the formation of more complex patterns. We discuss
      nucleation of the domain patterns by thermal fluctuations and pattern formation
      scenarios for various thermal quenches. We argue that self-induced disorder is an
      intrinsic property of the domain patterns in the systems under consideration.

PMID- 12513349
TI  - Nonequilibrium velocity distributions in liquids: systems under shear.
AB  - A Green-Kubo expression for the nonequilibrium correction to the velocity
      distribution function is studied in a molecular dynamics simulation for systems
      interacting through a 6-12 potential and undergoing linear shear. As a function
      of velocity, the first correction to the distribution function has a form similar
      to what would be obtained from the Boltzmann-Enskog equation, although the
      amplitude is qualitatively different, except at infinite dilution. The difference
      comes from elastic effects seen in the short-time behavior of the underlying time
      correlation functions.

PMID- 12513350
TI  - Cluster Monte Carlo simulation of the transverse Ising model.
AB  - We formulate a cluster Monte Carlo method for the anisotropic limit of Ising
      models on (d+1)-dimensional lattices, which in effect, are equivalent with d
      dimensional quantum transverse Ising models. Using this technique, we investigate
      the transverse Ising models on the square, triangular, Kagome, honeycomb, and
      simple-cubic lattices. The Monte Carlo data are analyzed by finite-size scaling.
      In each case we find, as expected, that the critical behavior fits well in the
      (d+1)-dimensional Ising universality class. For the transverse Ising model on the
      square lattice, we determine the Binder cumulant of the classical counterpart for
      a range of aspect ratios between the system sizes in the third or "classical"
      direction and that in the other two directions. Matching this universal function
      with the case of the isotropic Ising model yields the length ratio relating the
      isotropic Ising model with the anisotropic limit. The efficiency of the present
      algorithm is reflected by the precision of its results, which improves
      significantly on earlier analyses.

PMID- 12513351
TI  - Dynamics of ballistic annihilation.
AB  - The problem of ballistically controlled annihilation is revisited for general
      initial velocity distributions and an arbitrary dimension. An analytical
      derivation of the hierarchy equations obeyed by the reduced distributions is
      given, and a scaling analysis of the corresponding spatially homogeneous system
      is performed. This approach points to the relevance of the nonlinear Boltzmann
      equation for dimensions larger than 1 and provides expressions for the exponents
      describing the decay of the particle density n(t) proportional, variant t(-xi)
      and the root-mean-square velocity v proportional, variant t(-gamma) in terms of a
      parameter related to the dissipation of kinetic energy. The Boltzmann equation is
      then solved perturbatively within a systematic expansion in Sonine polynomials.
      Analytical expressions for the exponents xi and gamma are obtained in arbitrary
      dimension as a function of the parameter mu characterizing the small velocity
      behavior of the initial velocity distribution. Moreover, the leading non-Gaussian
      corrections to the scaled velocity distribution are computed. These expressions
      for the scaling exponents are in good agreement with the values reported in the
      literature for continuous velocity distributions in d=1. For the two-dimensional
      case, we implement Monte Carlo and molecular dynamics simulations that turn out
      to be in excellent agreement with the analytical predictions.

PMID- 12513352
TI  - Kinks of arbitrary width.
AB  - The influence of external potentials on kink width is investigated. The stability
      of a single kink and kink-antikink solutions in the presence of an external force
      is proved. The consequences of stability for defect production during a quench
      are discussed.

PMID- 12513353
TI  - Relaxation and overlap-probability function in the spherical and mean-spherical
      models.
AB  - The problem of the equivalence of the spherical and mean-spherical models, which
      has been thoroughly studied and is understood in equilibrium, is considered anew
      from the dynamical point of view during the time evolution following a quench
      from above to below the critical temperature. It is found that there exists a
      crossover time t(*) approximately V(2/d) such that for t<t(*) the two models are
      equivalent, while for t>t(*) macroscopic discrepancies arise. The relation
      between the off equilibrium response function and the structure of the
      equilibrium state that usually holds for phase ordering systems is found to hold
      for the spherical model but not for the mean-spherical one. The latter model
      offers an explicit example of a system which is not stochastically stable.

PMID- 12513354
TI  - Modulated scale-free network in Euclidean space.
AB  - A random network is grown by introducing at unit rate randomly selected nodes on
      the Euclidean space. A node is randomly connected to its ith predecessor of
      degree k(i) with a directed link of length l using a probability proportional to
      k(i)l(alpha). Our numerical study indicates that the network is scale free for
      all values of alpha>alpha(c) and the degree distribution decays stretched
      exponentially for the other values of alpha. The link length distribution follows
      a power law: D(l) approximately l(delta), where delta is calculated exactly for
      the whole range of values of alpha.

PMID- 12513355
TI  - Numerical study of the development of bulk scale-free structures upon growth of
      self-affine aggregates.
AB  - During the last decade, self-affine geometrical properties of many growing
      aggregates, originated in a wide variety of processes, have been well
      characterized. However, little progress has been achieved in the search of a
      unified description of the underlying dynamics. Extensive numerical evidence is
      given showing that the bulk of aggregates formed upon ballistic aggregation and
      random deposition with surface relaxation processes can be broken down into a set
      of infinite scale invariant structures called "trees." These two types of
      aggregates have been selected because it has been established that they belong to
      different universality classes: those of Kardar-Parisi-Zhang and Edward
      Wilkinson, respectively. Exponents describing the spatial and temporal scale
      invariance of the trees can be related to the classical exponents describing the
      self-affine nature of the growing interface. Furthermore, those exponents allow
      us to distinguish either the compact or noncompact nature of the growing trees.
      Therefore, the measurement of the statistic of the process of growing trees may
      become a useful experimental technique for the evaluation of the self-affine
      properties of some aggregates.

PMID- 12513356
TI  - Microstructure and velocity of field-driven solid-on-solid interfaces: analytic
      approximations and numerical results.
AB  - The local structure of a solid-on-solid interface in a two-dimensional kinetic
      Ising ferromagnet or attractive lattice-gas model with single-spin-flip Glauber
      dynamics, which is driven far from equilibrium by an applied field or chemical
      potential, is studied by an analytic mean-field, nonlinear-response theory [P. A.
      Rikvold and M. Kolesik, J. Stat. Phys. 100, 377 (2000)], and by dynamic Monte
      Carlo simulations. The probability density of the height of an individual step in
      the surface is obtained, both analytically and by simulation. The width of the
      probability density is found to increase dramatically with the magnitude of the
      applied field, with close agreement between the theoretical predictions and the
      simulation results. Excellent agreement between theory and simulations is also
      found for the field dependence and anisotropy of the interface velocity. The
      joint distribution of nearest-neighbor step heights is obtained by simulation. It
      shows increasing correlations with increasing field, similar to the skewness
      observed in other examples of growing surfaces.

PMID- 12513357
TI  - Phase-field model for front propagation in a temperature gradient: selection and
      competition between the correlation and the thermal lengths.
AB  - A phase-field model is presented to study the propagation and the selection of a
      front in directional growth. The phase transition can be first or second order
      and is described by a nonconserved order parameter. In general, the thermal
      length l(u) (inversely proportional to the temperature gradient) is much larger
      than the correlation length l(phi), which gives the width of the front, and there
      is no direct competition between them (epsilon =l(phi)/l(u)<<1). In this paper,
      we consider a situation where these two lengths can be of the same order of
      magnitude (epsilon =l(phi)/l(u) close to 1). This happens in liquid crystals at
      the nematic-cholesteric phase transition. The problem of the front selection is
      solved theoretically by first performing an asymptotic analysis of the governing
      equations in the limit epsilon-->0, and then by solving the equations
      numerically. The main result is that the front is selected in a single way (no
      continuum of solutions) as long as epsilon not equal 0, whatever the velocity and
      the order of the phase transition. Finally, we show that the order parameter
      profile and the front temperature can change significantly when epsilon
      approaches 1.

PMID- 12513358
TI  - Kang-Redner small-mass anomaly in cluster-cluster aggregation.
AB  - The large-time small-mass asymptotic behavior of the average mass distribution
      P(m,t) is studied in a d-dimensional system of diffusing aggregating particles
      for 1< or =d< or =2. By means of both a renormalization group computation as well
      as a direct resummation of leading terms in the small-reaction-rate expansion of
      the average mass distribution, it is shown that P(m,t) approximately
      (1/t(d))(m(1/d)/sqrt[t])(e(KR)) for m<<t(d/2), where e(KR)=epsilon+O(epsilon(2))
      and epsilon=2-d. In two dimensions, it is shown that P(m,t) approximately
      ln(m)ln(t)/t(2) for m<<t/ln(t). Numerical simulations in two dimensions
      supporting the analytical results are also presented.

PMID- 12513359
TI  - Quantum hydrodynamic equations and quantum-hierarchy decoupling scheme.
AB  - There is a need to extract the relevant device physics from exact quantum
      transport formulations, and hence to reduce the complexity of quantum transport
      simulations for practical applications. We use a Hermite polynomial expansion to
      drastically reduce the number of degrees of freedom associated with the momentum
      variables. The result is a quantum hierarchy in real space. We also give a
      general procedure for the quantum-hierarchy decoupling scheme to derive the
      quantum hydrodynamic (QHD) and quantum drift-diffusion transport equations. We
      present some numerical results for the quantum hierarchy. A rigorous foundation
      of a decoupling procedure is given whereby the lower-order equations are
      renormalized in terms of a self-consistent effective potential, quantum diffusion
      coefficient, and moments, endowed with all the quantum corrections to order
      variant Planck's over h(2). Our decoupling scheme is based on the general
      expression of Tr H(n) to order variant Planck's over h(2), valid at all
      temperatures without the need for expansion in terms of the small parameter and
      high temperature assumption. This is very important conceptually since existing
      QHD formulations, using expansion to order h(2), are based on a Boltzmann
      distribution with the restrictive assumption of a small parameter, which is not
      valid in abrupt heterojunction semiconductor devices. They also fail to account
      for important quantum nonlinearity in the form of nonequilibrium quantum
      corrections. These nonequilibrium quantum corrections are expected to play a
      major role in approximating the coherence manifested by the highly nonlinear
      current-voltage characteristics of resonant tunneling structures.

PMID- 12513360
TI  - Stable spiral structures and their interaction in two-dimensional excitable
      media.
AB  - We study properties and interactions of stable spiral structures in two
      dimensional excitable media modeled by equations of FitzHugh-Nagumo type. The
      presented results rely on the media ability to support unexcited spiral cores.
      Comparative frequency and dynamics analysis is done for a single spiral, an
      oppositely charged bound pair, and multiarmed spirals. Higher-frequency
      structures can attract, repel, or break up structures with lower frequencies. All
      pairwise reactions are described. A three-armed spiral and a two-armed spiral of
      opposite charge can form a stable "molecule." A system with high initial vortex
      concentration evolves according to the described reactions and exhibits three
      levels of self-organization. In our simulations such evolution led to formation
      and domination of persistent three-armed spirals.

PMID- 12513361
TI  - General formalism for inhomogeneous random graphs.
AB  - We present and investigate an extension of the classical random graph to a
      general class of inhomogeneous random graph models, where vertices come in
      different types, and the probability of realizing an edge depends on the types of
      its terminal vertices. This approach provides a general framework for the
      analysis of a large class of models. The generic phase structure is derived using
      generating function techniques, and relations to other classes of models are
      pointed out.

PMID- 12513363
TI  - Diffusion of the magnetization profile in the XX model.
AB  - We investigate the magnetization profile in the intermediate time of diffusion by
      using the C*-algebraic method. We observe a transition from monotone profile to
      nonmonotone profile. This transition is purely thermal.

PMID- 12513362
TI  - Quasistatic brittle fracture in inhomogeneous media and iterated conformal maps:
      modes I, II, and III.
AB  - The method of iterated conformal maps is developed for quasistatic fracture of
      brittle materials, for all modes of fracture. Previous theory, that was relevant
      for mode III only, is extended here to modes I and II. The latter require the
      solution of the bi-Laplace rather than the Laplace equation. For all cases we can
      consider quenched randomness in the brittle material itself, as well as
      randomness in the succession of fracture events. While mode III calls for the
      advance (in time) of one analytic function, modes I and II call for the advance
      of two analytic functions. This fundamental difference creates different stress
      distribution around the cracks. As a result the geometric characteristics of the
      cracks differ, putting mode III in a different class compared to modes I and II.

PMID- 12513364
TI  - Products of random matrices.
AB  - We derive analytic expressions for infinite products of random 2 x 2 matrices.
      The determinant of the target matrix is log-normally distributed, whereas the
      remainder is a surprisingly complicated function of a parameter characterizing
      the norm of the matrix and a parameter characterizing its skewness. The
      distribution may have importance as an uncommitted prior in statistical image
      analysis.

PMID- 12513365
TI  - Duality relations for elastic constants of the classical Gaussian core model.
AB  - The many-body Gaussian core model involves a potential energy function that
      consists of a sum of repelling pair interactions, each of which is a simple
      Gaussian function of distance. This paper examines the linear elastic response of
      the model for its stable lattices at absolute zero temperature, in D=1, 2, and 3
      dimensions. Owing to the fact that the Gaussian function is self-similar under
      Fourier transformation, exact relations exist connecting each elastic constant at
      number density rho to a partner at dual density rho(') in the reciprocal lattice,
      where rhorho(')=pi(-D). By using these identities, it has been possible to show
      that shear elastic constants in D=2 and 3 tend strongly to zero in the asymptotic
      high density limit.

PMID- 12513366
TI  - Statistical mechanics of lossy data compression using a nonmonotonic perceptron.
AB  - The performance of a lossy data compression scheme for uniformly biased Boolean
      messages is investigated via methods of statistical mechanics. Inspired by a
      formal similarity to the storage capacity problem in neural network research, we
      utilize a perceptron of which the transfer function is appropriately designed in
      order to compress and decode the messages. Employing the replica method, we
      analytically show that our scheme can achieve the optimal performance known in
      the framework of lossy compression in most cases when the code length becomes
      infinite. The validity of the obtained results is numerically confirmed.

PMID- 12513367
TI  - Stability of shortest paths in complex networks with random edge weights.
AB  - We study shortest paths and spanning trees of complex networks with random edge
      weights. Edges which do not belong to the spanning tree are inactive in a
      transport process within the network. The introduction of quenched disorder
      modifies the spanning tree such that some edges are activated and the network
      diameter is increased. With analytic random-walk mappings and numerical analysis,
      we find that the spanning tree is unstable to the introduction of disorder and
      displays a phase-transitionlike behavior at zero disorder strength epsilon =0. In
      the infinite network-size limit (N--> infinity ), we obtain a continuous
      transition with the density of activated edges Phi growing like Phi approximately
      epsilon (1) and with the diameter-expansion coefficient Upsilon growing like
      Upsilon approximately epsilon (2) in the regular network, and first-order
      transitions with discontinuous jumps in Phi and Upsilon at epsilon=0 for the
      small-world (SW) network and the Barabasi-Albert scale-free (SF) network. The
      asymptotic scaling behavior sets in when N>>N(c), where the crossover size scales
      as N(c) approximately epsilon (-2) for the regular network, N(c) approximately
      exp(alpha epsilon (-2)) for the SW network, and N(c) approximately exp(alpha|ln
      epsilon | epsilon (-2)) for the SF network. In a transient regime with N<<N(c),
      there is an infinite-order transition with Phi approximately Upsilon
      approximately exp[-alpha/(epsilon (2)ln N)] for the SW network and approximately
      exp[-alpha/(epsilon (2)ln N/ln ln N)] for the SF network. It shows that the
      transport pattern is practically most stable in the SF network.

PMID- 12513368
TI  - Approximation for directed percolation in d=1+1.
AB  - We introduce an approximation specific to a continuous variable formulation of
      directed percolation, which is strictly equivalent to (1+1)-dimensional directed
      bond percolation. We find that the critical exponent associated with the order
      parameter (percolation probability) is beta=(1-1/square root[5])/2=0.276 393 202
      em leader, in remarkable agreement with the best current numerical estimate
      beta=0.276 486(8).

PMID- 12513369
TI  - Critical temperature estimates for higher-spin Ising and Potts models.
AB  - We present estimates of the critical temperature of both higher-spin Ising and
      Potts models on the square and simple cubic lattices based on a Husimi tree,
      dynamical systems approach. For the square lattice, exact results are available
      for the Potts model but we can refine and improve some previous estimates based
      on series expansions for the higher-spin Ising model. For the simple cubic
      lattice, based on the systematics of this approach, we are able to present
      accurate estimates for the critical temperature of spin systems with spin values,
      where estimates by other methods are unavailable or much less accurate. The same
      is true for the Potts model. All our estimates can be obtained using a personal
      computer.

PMID- 12513370
TI  - Analytical approximation of the two-dimensional percolation threshold for fields
      of overlapping ellipses.
AB  - Percolation of particle arrays is of high interest in microstructural design of
      materials. While there have been numerous contributions to theoretical modeling
      of percolation in particulate systems, no analytical approximation for the
      generalized problem of variable aspect-ratio ellipses has been reported. In the
      present work, we (1) derive, and verify through simulation, an analytical
      percolation approach capable of identifying the percolation point in two-phase
      materials containing generalized ellipses of uniform shape and size; and (2)
      explore the dependence of percolation on the particle aspect ratio. We validate
      our technique with simulations tracking both cluster sizes and percolation
      status, in networks of elliptical and circular particles. We also outline the
      steps needed to extend our approach to three-dimensional particles (ellipsoids).
      For biological materials, we ultimately aim to provide direct insight into the
      contribution of each single phase in multiphase tissues to mechanical or
      conductive properties. For engineered materials, we aim to provide insight into
      the minimum amount of a particular phase needed to strongly influence properties.

PMID- 12513371
TI  - Polygonal billiards and transport: diffusion and heat conduction.
AB  - A detail study of the diffusive and heat conduction properties of a family of
      nonchaotic billiards is presented. For dynamical systems with dynamical
      instability the relation between transport properties and characteristic
      quantities of the chaotic dynamics naturally emerge. On the contrary, in
      dynamical systems without chaos (in the sense of exponential separation of nearby
      trajectories) much less is known. From numerical simulations we compute several
      quantities related to diffusion, such as the mean square displacement, the
      behavior of the hydrodynamic modes for long wavelengths, through the properties
      of the incoherent intermediate scattering function and the velocity
      autocorrelation function, in connection with the Green-Kubo formula. The analysis
      of all these quantities indicates that some systems among the family studied have
      normal diffusion and others anomalous diffusion. The spectral measure associated
      with the velocity autocorrelation function is also studied. The same analysis
      reveals that for all the systems treated there is not a well defined super
      Burnett coefficient. The heat conduction is also explored and found that,
      naturally, it is valid for the systems that behave diffusively.

PMID- 12513372
TI  - Paradoxical motion of a single Brownian particle: absolute negative mobility.
AB  - We consider a single, classical Brownian particle in a spatially symmetric
      periodic system far from thermal equilibrium, which can be readily realized
      experimentally. Upon application of an external static force F, the average
      particle velocity is negative for F>0 and positive for F<0 (absolute negative
      mobility). The various physical mechanisms responsible for such a paradoxical
      effect are identified, leading to analytical approximations that are in good
      agreement with numerical simulations.

PMID- 12513373
TI  - Local variational principle.
AB  - A generalization of the Gibbs-Bogoliubov-Feynman inequality for spinless
      particles is proven and then illustrated for the simple model of a symmetric
      double-well quartic potential. The method gives a pointwise lower bound for the
      finite-temperature density matrix and it can be systematically improved by the
      Trotter composition rule. It is also shown to produce ground state energies
      better than the ones given by the Rayleigh-Ritz principle as applied to the
      ground state eigenfunctions of the reference potentials. Based on this
      observation, it is argued that the local variational principle performs better
      than the equivalent methods based on the centroid path idea and on the Gibbs
      Bogoliubov-Feynman variational principle, especially in the range of low
      temperatures.

PMID- 12513374
TI  - Percolation in models of thin film depositions.
AB  - We have studied the percolation behavior of deposits for different (2+1)
      dimensional models of surface layer formation. The mixed model of deposition was
      used, where particles were deposited selectively according to the random (RD) and
      ballistic (BD) deposition rules. In the mixed one-component models with
      deposition of only conducting particles, the mean height of the percolation layer
      (measured in monolayers) grows continuously from 0.898 32 for the pure RD model
      to 2.605 for the pure BD model, but the percolation transition belongs to the
      same universality class, as in the two-dimensional (2D) random percolation
      problem. In two-component models with deposition of conducting and isolating
      particles, the percolation layer height approaches infinity as concentration of
      the isolating particles becomes higher than some critical value. The crossover
      transition from 2D to 3D percolation was observed with increase of the
      percolation layer height.

PMID- 12513375
TI  - Mutual learning in a tree parity machine and its application to cryptography.
AB  - Mutual learning of a pair of tree parity machines with continuous and discrete
      weight vectors is studied analytically. The analysis is based on a mapping
      procedure that maps the mutual learning in tree parity machines onto mutual
      learning in noisy perceptrons. The stationary solution of the mutual learning in
      the case of continuous tree parity machines depends on the learning rate where a
      phase transition from partial to full synchronization is observed. In the
      discrete case the learning process is based on a finite increment and a full
      synchronized state is achieved in a finite number of steps. The synchronization
      of discrete parity machines is introduced in order to construct an ephemeral key
      exchange protocol. The dynamic learning of a third tree parity machine (an
      attacker) that tries to imitate one of the two machines while the two still
      update their weight vectors is also analyzed. In particular, the synchronization
      times of the naive attacker and the flipping attacker recently introduced in Ref.
      9 are analyzed. All analytical results are found to be in good agreement with
      simulation results.

PMID- 12513376
TI  - Cluster approximation solution of a two-species annihilation model.
AB  - A two-species reaction-diffusion model, in which particles diffuse on a one
      dimensional lattice and annihilate when meeting each other, has been
      investigated. Mean-field equations for general choice of reaction rates have been
      solved exactly. The cluster mean-field approximation of the model is also
      studied. It is shown that the general form of large time behavior of one- and two
      point functions of the number operators are determined by the diffusion rates of
      the two type of species, and is independent of annihilation rates.

PMID- 12513377
TI  - Finite-size effects of avalanche dynamics.
AB  - We study the avalanche dynamics of a system of globally coupled threshold
      elements receiving random input. The model belongs to the same universality class
      as the random-neighbor version of the Olami-Feder-Christensen stick-slip model. A
      closed expression for avalanche size distributions is derived for arbitrary
      system sizes N using geometrical arguments in the system's configuration space.
      For finite systems, approximate power-law behavior is obtained in the
      nonconservative regime, whereas for N--> infinity, critical behavior with an
      exponent of -3/2 is found in the conservative case only. We compare these results
      to the avalanche properties found in networks of integrate-and-fire neurons, and
      relate the different dynamical regimes to the emergence of synchronization with
      and without oscillatory components.

PMID- 12513378
TI  - Generalized correlated states in a ring of coupled nonlinear oscillators with a
      local injection.
AB  - In this paper, we study the spatiotemporal dynamics of a ring of diffusely
      coupled nonlinear oscillators. Floquet theory is used to investigate the various
      dynamical states of the ring, as well as the Hopf bifurcations between them. A
      local injection scheme is applied to synchronize the ring with an external master
      oscillator. The shift-invariance symmetry is thereby broken, leading to the
      emergence of generalized correlated states. The transition boundaries from these
      correlated states to spatiotemporal chaos and complete synchronization are also
      derived. Numerical simulations are performed to support the analytic approach.

PMID- 12513379
TI  - Front instabilities in a forced oscillatory medium with global coupling.
AB  - We study a two-dimensional, locally and globally coupled oscillatory system that
      is subjected to external forcing at a frequency equal to twice its natural
      frequency. It is shown that the onset of an Ising-Bloch transition is preceded by
      novel front instabilities: a pattern formation instability, wave trains along the
      front, and a weak turbulence in the frontal patterns.

PMID- 12513380
TI  - Master equation approach to the conjugate pairing rule of Lyapunov spectra for
      many-particle thermostated systems.
AB  - The master equation approach to Lyapunov spectra for many-particle systems is
      applied to nonequilibrium thermostated systems to discuss the conjugate pairing
      rule. We consider iso-kinetic thermostated systems with a shear flow sustained by
      an external restriction, in which particle interactions are expressed as a
      Gaussian white randomness. Positive Lyapunov exponents are calculated by using
      the Fokker-Planck equation to describe the tangent vector dynamics. We introduce
      another Fokker-Planck equation to describe the time-reversed tangent vector
      dynamics, which leads to the calculation of the negative Lyapunov exponents.
      Using the Lyapunov exponents provided by these two Fokker-Planck equations we
      show the conjugate pairing rule is satisfied for thermostated systems with a
      shear flow in the thermodynamic limit which allow us to replace the friction
      coefficient with a constant number. We also give an explicit form to connect the
      Lyapunov exponents with the time correlation of the interaction matrix in a
      thermostated system with a color field.

PMID- 12513381
TI  - Front and pulse solutions for the complex Ginzburg-Landau equation with higher
      order terms.
AB  - We investigate one-dimensional complex Ginzburg-Landau equation with higher-order
      terms and discuss their influences on the multiplicity of solutions. An exact
      analytic front solution is presented. By stability analysis for the original
      partial differential equation, we derive its necessary stability condition for
      amplitude perturbations. This condition together with the exact front solution
      determine the region of parameter space where the uniformly translating front
      solution can exist. In addition, stable pulses, chaotic pulses, and attenuation
      pulses appear generally if the parameters are out of the range. Finally, applying
      these analysis into the optical transmission system numerically we find that the
      stable transmission of optical pulses can be achieved if the parameters are
      appropriately chosen.

PMID- 12513382
TI  - Characterization of the stretched-exponential trap-time distributions in one
      dimensional coupled map lattices.
AB  - Stretched-exponential distributions and relaxation responses are encountered in a
      wide range of physical systems such as glasses, polymers, and spin glasses. As
      found recently, this type of behavior occurs also for the distribution function
      of a certain trap time in a number of coupled dynamical systems. We analyze a one
      dimensional mathematical model of coupled chaotic oscillators that reproduces an
      experimental setup of coupled diode resonators and identify the necessary
      ingredients for stretched-exponential distributions.

PMID- 12513383
TI  - Autocatalytic model of oscillatory zoning in experimentally grown (Ba,Sr)SO4
      solid solution.
AB  - Oscillatory zoning (OZ) is a phenomenon common to many natural minerals whereby
      the mineral composition varies more or less regularly from the core of the
      crystal to its rim. Oscillatory zoned barite-celestite (Ba,Sr)SO4 crystals are
      one of the very few examples of the OZ phenomenon that were obtained under
      controlled laboratory conditions. It is known that such crystals can be
      synthesized by precipitation from an aqueous solution during counterdiffusion in
      a gel column connecting two reservoirs. We present here a model of oscillatory
      zoning in such a binary solid solution grown from an aqueous solution. By
      expanding on a previously suggested model, we obtain oscillatory dynamical
      solutions for two limit cases: the growth of a flat crystal face and the growth
      of a spherical crystallite. We consider an autocatalytic dependence between the
      crystal growth rate and the crystal surface composition. The oscillatory patterns
      then arise as a kinetic effect due to the coupling between the diffusion field
      around the crystal and the fast crystal growth under far-from-equilibrium
      conditions. The effects of fluctuations in the aqueous solution concentrations
      are also considered. It is shown that they may lead to noisy oscillatory
      patterns.

PMID- 12513384
TI  - Statistics of finite-time Lyapunov exponents in a random time-dependent
      potential.
AB  - The sensitivity of trajectories over finite-time intervals t to perturbations of
      the initial conditions can be associated with a finite-time Lyapunov exponent
      lambda, obtained from the elements M(ij) of the stability matrix M. For globally
      chaotic dynamics, lambda tends to a unique value (the usual Lyapunov exponent
      lambda(infinity)) for almost all trajectories as t is sent to infinity, but for
      finite t it depends on the initial conditions of the trajectory and can be
      considered as a statistical quantity. We compute for a particle moving in a
      randomly time-dependent, one-dimensional potential how the distribution function
      P(lambda;t) approaches the limiting distribution P(lambda; infinity)=delta(lambda
      lambda(infinity)). Our method also applies to the tail of the distribution, which
      determines the growth rates of moments of M(ij). The results are also applicable
      to the problem of wave-function localization in a disordered one-dimensional
      potential.

PMID- 12513385
TI  - Excitable media in open and closed chaotic flows.
AB  - We investigate the response of an excitable medium to a localized perturbation in
      the presence of a two-dimensional smooth chaotic flow. Two distinct types of
      flows are numerically considered: open and closed. For both of them three
      distinct regimes are found, depending on the relative strengths of the stirring
      and the rate of the excitable reaction. In order to clarify and understand the
      role of the many competing mechanisms present, simplified models of the process
      are introduced. They are one-dimensional baker-map models for the flow and a one
      dimensional approximation for the transverse profile of the filaments observed in
      the concentration patterns.

PMID- 12513386
TI  - Signature of on-off intermittency in measured signals.
AB  - On-off intermittency is a phase-space mechanism that allows dynamical systems to
      undergo bursting. As its name suggests, bursting is a phenomenon in which
      episodes of high activity are alternated with periods of inactivity. Here we
      attempt to see whether we can tell from the output of a signal when an observed
      bursting behavior is caused by the presence of on-off intermittency, using the
      example of a forced logistic map. The results of our study indicate that on-off
      intermittency can be readily distinguished from other mechanisms for bursting we
      know of, except for one. Many statistical properties of finite-length signals
      generated by on-off intermittency can in fact be mimicked by the output of a
      nonlinearly filtered, linear autoregressive random process.

PMID- 12513387
TI  - Quantum manifestations of classical periodic orbits in a square billiard:
      formation of vortex lattices.
AB  - We extend the presentation of the SU(2) coherent states to analytically construct
      the wave function concentrated on high-order classical periodic orbits in a
      square billiard. With the constructed wave function, the localization of the wave
      pattern is found to be very efficient. We also analyze the vortices arising from
      the singular points of the quantum phase for the constructed coherent states. It
      is found that the wave interference gives rise to the appearance of vortex
      lattices in the probability current density associated with the high-order
      periodic orbits. Moreover, the topological charge of the vortex is in general
      nonintegral except for the periodic orbits with the same winding number to the
      sides of the square.

PMID- 12513388
TI  - Wave chaos in the elastic disk.
AB  - The relation between the elastic wave equation for plane, isotropic bodies and an
      underlying classical ray dynamics is investigated. We study, in particular, the
      eigenfrequencies of an elastic disk with free boundaries and their connection to
      periodic rays inside the circular domain. Even though the problem is separable,
      wave mixing between the shear and pressure component of the wave field at the
      boundary leads to an effective stochastic part in the ray dynamics. This
      introduces phenomena typically associated with classical chaos as, for example,
      an exponential increase in the number of periodic orbits. Classically, the
      problem can be decomposed into an integrable part and a simple binary Markov
      process. Similarly, the wave equation can, in the high-frequency limit, be mapped
      onto a quantum graph. Implications of this result for the level statistics are
      discussed. Furthermore, a periodic trace formula is derived from the scattering
      matrix based on the inside-outside duality between eigenmodes and scattering
      solutions and periodic orbits are identified by Fourier transforming the spectral
      density.

PMID- 12513389
TI  - Two-dimensional maps at the edge of chaos: numerical results for the Henon map.
AB  - The mixing properties (or sensitivity to initial conditions) of the two
      dimensional Henon map have been explored numerically at the edge of chaos. Three
      independent methods, which have been developed and used so far for one
      dimensional maps, have been used to accomplish this task. These methods are (i)
      the measure of the divergence of initially nearby orbits, (ii) analysis of the
      multifractal spectrum, and (iii) computation of nonextensive entropy increase
      rates. The results obtained closely agree with those of the one-dimensional cases
      and constitute a verification of this scenario in two-dimensional maps. This
      obviously makes the idea of weak chaos even more robust.

PMID- 12513390
TI  - Pinning stationary planar fronts in diffusion-convection-reaction systems.
AB  - This paper considers various strategies for controlling a stationary planar front
      solution, in a rectangular domain with a diffusion-reaction distributed system,
      by pinning the solution to one or few points and using actuators with the
      simplest possible spatial dependence. We review previous results obtained for one
      dimensional diffusion-reaction (with or without convection) systems, for which we
      applied two approaches: an approximate model reduction to a form that follows the
      front position while approximating the front velocity, and linear stability
      analysis. We apply the same two approaches for the planar fronts. The approximate
      model reduction allows us to analyze qualitatively various control strategies and
      to predict the critical width below which the control mode of the one-dimensional
      system is sufficient. These results are corroborated by linear analysis of a
      truncated model with the spectral methods representation, using concepts of
      finite and infinite zeros of linear multidimensional systems.

PMID- 12513391
TI  - On-off intermittency and intermingledlike basins in a granular medium.
AB  - Molecular dynamic simulations of a medium consisting of disks in a periodically
      tilted box yield two dynamic modes differing considerably in the total potential
      and kinetic energies of the disks. Depending on parameters, these modes display
      the following features: (i) hysteresis (coexistence of the two modes in phase
      space); (ii) intermingledlike basins of attraction (uncertainty exponent
      indistinguishable from zero); (iii) two-state on-off intermittency; and (iv)
      bimodal velocity distributions. Bifurcations are defined by a cross-shaped phase
      diagram.

PMID- 12513392
TI  - Low symmetry patterns on magnetic fluids.
AB  - The pattern formation on the free surface of a magnetic fluid subjected
      simultaneously to a vertical and a horizontal magnetic field is investigated
      theoretically. In this anisotropic system planforms less symmetric then squares
      and hexagons arise. The relative stability of parallel ridges and asymmetric
      patterns, periodic on a rectangular or a rhombic lattice, is studied using a
      perturbative energy minimization procedure. Moreover, the interplay between the
      anisotropy and the broken up-down symmetry of the system is quantitatively
      analyzed.

PMID- 12513393
TI  - Time-modulated oscillatory structures in phase-separating reactive mixtures.
AB  - We investigate the effect of temporal modulation on the spatiotemporal patterns
      produced by phase separation in chemically reactive ternary mixtures. The
      temporal modulation is introduced by making one of the reaction rates periodic in
      time. Our main concern is the stability of traveling waves, which appear above a
      Hopf-type bifurcation at a finite wave number and are stable in the absence of
      external modulation. It is shown by computer simulations in two dimensions that
      when the external modulation is present, various types of coherent standing waves
      emerge near the special point in the parameter space, where the Turing-type
      bifurcation line and the Hopf-type bifurcation line meet each other. We carry out
      a theoretical analysis to understand the phase diagram of the synchronized
      oscillatory structures obtained numerically.

PMID- 12513394
TI  - Fluctuation formula for nonreversible dynamics in the thermostated Lorentz gas.
AB  - We investigate numerically the validity of the Gallavotti-Cohen fluctuation
      formula in the two- and three-dimensional periodic Lorentz gas subjected to
      constant electric and magnetic fields and thermostated by the Gaussian isokinetic
      thermostat. The magnetic field breaks the time reversal symmetry, and by choosing
      its orientation with respect to the lattice, one can have either a generalized
      reversing symmetry or no reversibility at all. Our results indicate that the
      scaling property described by the fluctuation formula may be approximately valid
      for large fluctuations even in the absence of reversibility.

PMID- 12513395
TI  - Dynamics of "leaking" Hamiltonian systems.
AB  - In order to understand the dynamics in more detail, in particular for visualizing
      the space-filling unstable foliation of closed chaotic Hamiltonian systems, we
      propose to leak them up. The cutting out of a finite region of their phase space,
      the leak, through which escape is possible, leads to transient chaotic behavior
      of nearly all the trajectories. The never-escaping points belong to a chaotic
      saddle whose fractal unstable manifold can easily be determined numerically. It
      is an approximant of the full Hamiltonian foliation, the better the smaller the
      leak is. The escape rate depends sensitively on the orientation of the leak even
      if its area is fixed. The applications for chaotic advection, for chemical
      reactions superimposed on hydrodynamical flows, and in other branches of physics
      are discussed.

PMID- 12513396
TI  - Single-bubble sonoluminescence from noble gas mixtures.
AB  - Light emission intensities from single-bubble sonoluminescence at room
      temperature, water dissolved with admixtures of pairs of noble gases, He-Ar and
      He-Xe, were measured as a function of mixing ratio to search for effects of
      species segregation occurring during the violent bubble collapse. The observed
      relative effect on the light emission intensity is surprisingly greater in He-Ar
      than in a He-Xe mixture.

PMID- 12513397
TI  - Numerical simulations of the evolution of Taylor cells from a growing boundary
      layer on the inner cylinder of a high radius ratio Taylor-Couette system.
AB  - The Taylor-Couette flow in the gap between two concentric cylinders has been
      studied numerically to show the evolution of Taylor vortices from pairs of ring
      shaped vortices, at Reynolds numbers of 5 x 10(3) and 8 x 10(3) based upon the
      gap width. The cylinders have a high radius ratio of 0.985 and the inner cylinder
      rotates within a stationary outer cylinder. Initially, ring-shaped vortices are
      generated at the surface of the inner cylinder and spread into the gap. This is
      distinctly different from the formation of laminar Taylor vortices that grow from
      the end walls. Mixing of these ring-shaped vortices with the developing Couette
      flow then occurs and further ring-shaped vortices are generated. Some of these
      dominate the flow and begin to form Taylor vortices. Finally the Taylor vortices
      are stabilized and further vortex formation ceases. An analysis is also presented
      of the variation of shear stress with time.

PMID- 12513398
TI  - Realizability of stationary spherically symmetric transonic accretion.
AB  - The spherically symmetric stationary transonic (Bondi) flow is considered a
      classic example of an accretion flow. This flow, however, is along a separatrix,
      which is usually not physically realizable. We demonstrate, using a pedagogical
      example, that it is the dynamics which selects the transonic flow.

PMID- 12513399
TI  - Venusian "hot spots": physical phenomenon and its quantification.
AB  - An overall picture of the Venusian hot spots phenomenon is considered in the
      framework of the simplest conceptual models that admit the solutions in the form
      of steadily rotating "hot" vortices. Model assumptions take into account only
      those features of the middle atmosphere in the polar region of Venus that are
      supported by observational data and are essential for understanding the physical
      mechanism initiating similar vortices. The problem is analyzed in the framework
      of both the pointlike and petal-like models of cyclostrophic vortices.
      Interpretation of these models as an upper and lower bound of a complete theory
      allows one to find the region of existence of the regimes responsible for the
      Venusian hot spots and also to establish and assess numerically conditions under
      which such vortices can be formed. The emphasis is on a comparison of the
      theoretically established results with the observational data.

PMID- 12513400
TI  - Formation of large-scale semiorganized structures in turbulent convection.
AB  - A new mean-field theory of turbulent convection is developed by considering only
      the small-scale part of spectra as "turbulence" and the large-scale part, as a
      "mean flow," which includes both regular and semiorganized motions. The developed
      theory predicts the convective wind instability in a shear-free turbulent
      convection. This instability causes formation of large-scale semiorganized fluid
      motions in the form of cells. Spatial characteristics of these motions, such as
      the minimum size of the growing perturbations and the size of perturbations with
      the maximum growth rate, are determined. This study predicts also the existence
      of the convective shear instability in a sheared turbulent convection. This
      instability causes formation of large-scale rolls and generation of convective
      shear waves which have a nonzero hydrodynamic helicity. Increase of shear
      promotes excitation of the convective shear instability. Applications of the
      obtained results to the atmospheric turbulent convection and the laboratory
      experiments on turbulent convection are discussed.

PMID- 12513401
TI  - Large-scale spiral structures in turbulent thermal convection between two
      vertical plates.
AB  - By means of a three-dimensional numerical simulation of the Boussinesq equations,
      it is observed that the turbulent flow induced by thermal convection between two
      differentially heated vertical plates can generate strongly spiral structures on
      large scales. In this paper, the flow patterns and the temporal evolution of such
      large-scale spiral structures are manifested. It is shown that the length scale
      of the spiral structures is comparable to the width of the convection layer and
      their lifetime is about two or three orders of magnitude longer than that of
      small-scale structures of the turbulence. To understand the physical mechanism of
      the emergence of such structures, a topological interpretation of generating the
      structures and the role of helicity in preserving the structures are investigated
      and discussed.

PMID- 12513402
TI  - Lagrangian statistics and temporal intermittency in a shell model of turbulence.
AB  - We study the statistics of single-particle Lagrangian velocity in a shell model
      of turbulence. We show that the small-scale velocity fluctuations are
      intermittent, with scaling exponents connected to the Eulerian structure function
      scaling exponents. The observed reduced scaling range is interpreted as a
      manifestation of the intermediate dissipative range, as it disappears in a
      Gaussian model of turbulence.

PMID- 12513403
TI  - Weak fountains in a stratified fluid.
AB  - The behavior of weak axisymmetric and plane fountains resulting from the
      injection of denser fluid upwards into large containers containing a stably
      stratified fluid has been explored using dimensional analysis, scaling analysis,
      and direct numerical simulation. For weak fountains, with Froude number Fr
      approximately 1.0, dimensional and scaling analyses have been used to derive
      scaling relations for the dimensionless fountain height, width, thickness of the
      temperature layer, and development times in terms of the Froude number Fr,
      Reynolds number Re, Prandtl number Pr, and ambient stratification number s.
      Numerical simulations have been carried out for a series of Fr, Re, Pr, and s for
      both axisymmetric and plane fountains to validate and quantify the scaling
      relations obtained by the dimensional and scaling analyses. The numerical results
      have been found to agree well with the analytical scaling relations.

PMID- 12513404
TI  - Scenarios for the onset of convection close to the critical point.
AB  - We perform a theoretical analysis of the onset of convection in a layer of near
      critical 3He submitted to an unsteady bottom heating. A theoretical model
      previously presented [P. Carles, Physica D 147, 36 (2000)] is adapted to the
      corresponding physical conditions, and a method is proposed to solve the
      associated equations. We predict, for different intensities of heating and
      different initial temperatures, when convection will start and what will be the
      shape of the dominant growing perturbations. A systematic parametric analysis
      shows that the onset of convection in a supercritical fluid can take place
      following four distinct scenarios, depending on the initial temperature and the
      intensity of the heating. Two of these scenarios are entirely specific to near
      critical fluids, being impossible to observe in classical Boussinesq fluids.

PMID- 12513405
TI  - Stochastic analysis of a non-normal dynamical system mimicking a laminar-to
      turbulent subcritical transition.
AB  - The effects of stochastic perturbations on a non-normal dynamical system
      mimicking a laminar-to-turbulent subcritical transition are investigated both
      analytically and numerically. It is found that a nonlinear dynamical system with
      non-normal transient linear growth is very sensitive to the presence of weak
      random perturbations. The effect of non-normality on the exit probability from
      the zero fixed point is analyzed numerically for small values of the noise
      intensity parameter. It is found that an increase in the intensity of the noise,
      or a decrease of the non-normality parameter leads to qualitative changes in the
      behavior of the trajectories that can be interpreted as noise-induced phase
      transitions. By using the Ito formula and the adiabatic elimination procedure a
      stochastic equation governing the slow evolution of the energy of the non-normal
      system is derived.

PMID- 12513406
TI  - Gas heating in low-pressure microwave argon discharges.
AB  - Both an energy balance equation and a collisional-radiative model were developed
      in order to discover which process is responsible for gas heating in a low
      pressure argon discharge. In this way, for a wide range of plasma conditions, the
      space-charge field contribution to gas heating was found to be negligible
      compared to that resulting from elastic collisional processes, although the value
      of the former is higher than the latter when calculating the absorbed power per
      electron. This is due to (1) the heating associated with the space-charge field
      only being effective in the plasma sheath, which is very close to the vessel
      inner wall. (2) The vessel temperature value at the external wall is taken as a
      boundary condition, as a result of which the space-charge field influence on gas
      heating is indirectly imposed on the model. The results of the collisional
      radiative model take into account the influence of gas heating on the electron
      temperature and on the argon low-lying excited levels. Two different zones have
      been found. The first corresponds to low electron densities, in which the gas
      temperature remains constant, whereas in the second (high electron densities) the
      heating of the gas takes on great importance. These results compare well with
      experimental data.

PMID- 12513407
TI  - Relativistic electron generation in interactions of a 30 TW laser pulse with a
      thin foil target.
AB  - Energy and angular distributions of the fast outgoing electron beam induced by
      the interaction of a 1 J, 30 fs, 2 x 10(19) W/cm(2), 10 Hz laser with a thin foil
      target are characterized by electron energy spectroscopy and photonuclear
      reactions. We have investigated the effect of the target thickness and the
      intensity contrast ratio level on the electron production. Using a 6-microm
      polyethylene target, up to 4 x 10(8) electrons with energies between 5 and 60 MeV
      were produced per laser pulse and converted to gamma rays by bremsstrahlung in a
      Ta secondary target. The rates of photofission of U as well as photonuclear
      reactions in Cu, Au, and C samples have been measured. In optimal focusing
      conditions, about 0.06% of the laser energy has been converted to outgoing
      electrons with energies above 5 MeV. Such electrons leave the target in the laser
      direction with an opening angle of 2.5 degrees.

PMID- 12513408
TI  - Experimental and theoretical Stark broadening studies of the hydrogen Paschen
      beta line.
AB  - Experimental and theoretical Stark broadening studies of the Paschen beta line of
      hydrogen (lambda=1.28 microm) are reported. Line shape measurements were
      performed at electron densities of the plasma between 3.5 x 10(15) cm(-3) and 7.5
      x 10(15) cm(-3), applying as the light source a wall-stabilized arc operated at
      atmospheric pressure in a helium-hydrogen gas mixture. The radiation of the
      plasma, emitted from nearly homogeneous plasma layers in the end-on direction,
      was registered with the use of a grating spectrometer equipped with a charge
      coupled device detector. The measured light outputs were calibrated against
      signals obtained from a tungsten strip radiation standard. The experimentally
      determined line profiles are compared with results of new Stark broadening
      calculations based on simulation techniques. The measured broadening, shift, and
      asymmetry parameters are also compared with results of previous Stark broadening
      calculations and other experimental data obtained at electron densities higher as
      well as lower than ours.

PMID- 12513409
TI  - Spectroscopy of heliumlike argon resonance and satellite lines for plasma
      temperature diagnostics.
AB  - The n=2-1 spectral emission pattern of heliumlike argon, together with the
      associated satellite emission originating from lithiumlike argon have been
      measured with high-resolution x-ray spectroscopy at the Berlin electron-beam ion
      trap. The observed line intensity across a wide range of excitation energies was
      weighted by an electron-energy distribution to analyze as a function of plasma
      temperature the line ratios between KLL dielectronic recombination satellites, in
      particular the j+z, j, and k satellites, and the w-resonance line. A good
      agreement between various theoretical models is found, supporting the method of
      line-ratio measurement as a temperature diagnostic for plasmas. A value for the
      so-called R-line ratio is determined and calculations with the HULLAC suite of
      codes predict it to be electron density independent over a wide range.

PMID- 12513410
TI  - Hydrodynamic flow of ions and atoms in partially ionized plasmas.
AB  - We have derived the hydrodynamic equations of motion for a partially ionized
      plasma, when the ionized component and the neutral components have different flow
      velocities and kinetic temperatures. Starting from the kinetic equations for a
      gas of ions and a gas of atoms we have considered various processes of encounters
      between the two species: self-collisions, interspecies collisions, ionization,
      recombination, and charge exchange. Our results were obtained by developing a
      general approach for the hydrodynamics of a gas in a binary mixture, in
      particular when the components drift with respect to each other. This was applied
      to a partially ionized plasma, when the neutral-species gas and the charged
      species gas have separate velocities. We have further suggested a generalized
      version of the relaxation time approximation and obtained the contributions of
      the interspecies encounters to the transport equations.

PMID- 12513411
TI  - Laser-generated plasma plume expansion: combined continuous-microscopic modeling.
AB  - The physical phenomena involved in the interaction of a laser-generated plasma
      plume with a background gas are studied numerically. A three-dimensional combined
      model is developed to describe the plasma plume formation and its expansion in
      vacuum or into a background gas. The proposed approach takes advantages of both
      continuous and microscopic descriptions. The simulation technique is suitable for
      the simulation of high-rate laser ablation for a wide range of background
      pressure. The model takes into account the mass diffusion and the energy exchange
      between the ablated and background species, as well as the collective motion of
      the ablated species and the background-gas particles. The developed approach is
      used to investigate the influence of the background gas on the expansion dynamics
      of the plume obtained during the laser ablation of aluminum. At moderate
      pressures, both plume and gas compressions are weak and the process is mainly
      governed by the diffusive mixing. At higher pressures, the interaction is
      determined by the plume-gas pressure interplay, the plume front is strongly
      compressed, and its center exhibits oscillations. In this case, the snowplough
      effect takes place, leading to the formation of a compressed gas layer in front
      of the plume. The background pressure needed for the beginning of the snowplough
      effect is determined from the plume and gas density profiles obtained at various
      pressures. Simulation results are compared with experimentally measured density
      distributions. It is shown that the calculations suggest localized formation of
      molecules during reactive laser ablation.

PMID- 12513412
TI  - Temperature-dependent pseudopotential between two pointlike electrical charges.
AB  - Pair distribution functions for particles electrically charged, at a temperature
      T expressed in terms of density matrices and corresponding pseudopotentials are
      studied, for distinguishable particles and for an electron pair. Expansions with
      respect to the separation distance and to a quantum parameter (approximately T(
      1/2)) are carried out. Approximate expressions are derived in the limits of high
      and low temperatures.

PMID- 12513413
TI  - Metamorphosis of plasma turbulence-shear-flow dynamics through a transcritical
      bifurcation.
AB  - The structural properties of an economical model for a confined plasma turbulence
      governor are investigated through bifurcation and stability analyses. A close
      relationship is demonstrated between the underlying bifurcation framework of the
      model and typical behavior associated with low- to high-confinement transitions
      such as shear-flow stabilization of turbulence and oscillatory collective action.
      In particular, the analysis evinces two types of discontinuous transition that
      are qualitatively distinct. One involves classical hysteresis, governed by
      viscous dissipation. The other is intrinsically oscillatory and nonhysteretic,
      and thus provides a model for the so-called dithering transitions that are
      frequently observed. This metamorphosis, or transformation, of the system
      dynamics is an important late side-effect of symmetry breaking, which manifests
      as an unusual nonsymmetric transcritical bifurcation induced by a significant
      shear-flow drive.

PMID- 12513414
TI  - Temporal evolution of drift Alfven waves and instabilities in an inhomogeneous
      plasma with homogeneous shear flow.
AB  - The temporal evolution of drift Alfven waves in an inhomogeneous plasma of low
      and finite pressure with homogeneous shear flow is studied as an initial value
      problem without the use of spectral expansion in time. The cases of plasma with
      cold and hot ions, weak and strong flow shear are considered separately. It is
      shown that the conventional modal structure of the stable and unstable drift and
      Alfven waves holds only for a limited time in the initial stage of its evolution.
      For larger times, nonmodal effects due to the velocity shear define the
      development of drift Alfven waves and drift Alfven instabilities. For the regimes
      of low flow shear, which corresponds to the period of the low-to-high transition,
      the long time evolution of these instabilities as well as their saturation are
      determined by the nonlinear effects such as the nonlinear decorrelation effect.
      In contrast, the plasma with strong flow shear, which corresponds to the regime
      of the developed transport barriers, is stable against the development
      hydrodynamic drift Alfven and resistive drift Alfven instabilities. The frequency
      increase caused by the shear flow brings the Alfven wave phase speed close to the
      electron thermal speed where strong electron Landau damping occurs. At this
      stage, a kinetic approach for the description of these waves becomes necessary.

PMID- 12513415
TI  - Transition from Townsend to glow discharge: subcritical, mixed, or supercritical
      characteristics.
AB  - The transition from Townsend to glow discharge is investigated numerically in one
      space dimension in full parameter space within the classical model: with
      electrons and positive ions drifting in the local electric field, impact
      ionization by electrons (alpha process), secondary electron emission from the
      cathode (gamma process) and space charge effects. We also perform a systematic
      analytical small current expansion about the Townsend limit up to third order in
      the current that fits our numerical data very well. Depending on the two
      determining parameters gamma and system size pd, the transition from Townsend to
      glow discharge can show the textbook subcritical behavior, but for smaller values
      of pd, we also find supercritical or some unexpected intermediate "mixed"
      behavior. Our work shows the same qualitative dependence of U=U(I,pd) for fixed
      gamma as the old experiments by Pokrovskaya-Soboleva and Klyarfeld. Furthermore,
      the analysis lays the basis for understanding the complex spatiotemporal patterns
      in short planar barrier discharge systems.

PMID- 12513416
TI  - Electron energy distributions and anomalous skin depth effects in high-plasma
      density inductively coupled discharges.
AB  - Electron transport in low pressure (<10s mTorr), moderate frequency (<10s MHz)
      inductively coupled plasmas (ICPs) displays a variety of nonequilibrium
      characteristics due to their operation in a regime where the mean free paths of
      electrons are significant fractions of the cell dimensions and the skin depth is
      anomalous. Proper analysis of transport for these conditions requires a kinetic
      approach to resolve the dynamics of the electron energy distribution (EED) and
      its non-Maxwellian character. To facilitate such an investigation, a method was
      developed for modeling electron-electron collisions in a Monte Carlo simulation
      and the method was incorporated into a two-dimensional plasma equipment model.
      Electron temperatures, electron densities, and EEDs obtained using the model were
      compared with measurements for ICPs sustained in argon. It was found that EEDs
      were significantly depleted at low energies in regimes dominated by
      noncollisional heating, typically within the classical electromagnetic skin
      depth. Regions of positive and negative power deposition were observed for
      conditions where the absorption of the electric field was both monotonic and
      nonmonotonic.

PMID- 12513417
TI  - Time-resolved plasma spectroscopy of thin foils heated by a relativistic
      intensity short-pulse laser.
AB  - Time-resolved K-shell x-ray spectra are recorded from sub-100 nm aluminum foils
      irradiated by 150-fs laser pulses at relativistic intensities of Ilambda(2)=2 x
      10(18) W microm(2)/cm(2). The thermal penetration depth is greater than the foil
      thickness in these targets so that uniform heating takes place at constant
      density before hydrodynamic motion occurs. The high-contrast, high-intensity
      laser pulse, broad spectral band, and short time resolution utilized in this
      experiment permit a simplified interpretation of the dynamical evolution of the
      radiating matter. The observed spectrum displays two distinct phases. At early
      time, < or =500 fs after detecting target emission, a broad quasicontinuous
      spectral feature with strong satellite emission from multiply excited levels is
      seen. At a later time, the He-like resonance line emission is dominant. The time
      integrated data is in accord with previous studies with time resolution greater
      than 1 ps. The early time satellite emission is shown to be a signature of an
      initial large area, high density, low-temperature plasma created in the foil by
      fast electrons accelerated by the intense radiation field in the laser spot. We
      conclude that, because of this early time phenomenon and contrary to previous
      predictions, a short, high-intensity laser pulse incident on a thin foil does not
      create a uniform hot and dense plasma. The heating mechanism has been studied as
      a function of foil thickness, laser pulse length, and intensity. In addition, the
      spectra are found to be in broad agreement with a hydrodynamic expansion code
      postprocessed by a collisional-radiative model based on superconfiguration
      average rates and on the unresolved transition array formalism.

PMID- 12513418
TI  - Complex atomic spectral line shapes in the presence of an external magnetic
      field.
AB  - Both the theoretical basis and the computational approach for extending the
      capabilities of an established spectral line broadening code are presented. By
      following standard line broadening theory, the effects of an external magnetic
      field are incorporated into the plasma average and atomic Hamiltonian. An
      external magnetic field introduces a preferential axis that destroys the symmetry
      of the quasistatic electric ion microfield. An external magnetic field also
      modifies the angular properties of the atomic Hamiltonian-atomic energy levels
      are perturbed and the spectral emission line is polarized. These extensions have
      been incorporated in an atomic line shape code for complex atoms and applied to
      several problems of importance to the understanding of tokamak edge plasmas.
      Applications fall into two broad categories: (1) determination of local plasma
      properties, such as the magnetic field strength, from distinct line shape
      features; and (2) consideration of global plasma phenomenon, such as radiation
      transport. Observable features of the Zeeman effect make H(alpha) a good line for
      diagnosing the magnetic field. H(beta) does not make a good electron density
      diagnostic since the Zeeman effect is comparable to the Stark effect for a
      majority of tokamak edge plasma conditions. For optically thick lines, the
      details of the spectral line shapes are shown to significantly influence the
      transport of radiation throughout the system.

PMID- 12513419
TI  - Influence of the electron distribution function shape on nonlocal electron heat
      transport in laser-heated plasmas.
AB  - A nonlocal model of electron heat flow in laser-heated plasmas taking into
      account the super-Gaussian deformation of the electron velocity distribution
      function by the laser heating was developed. Based on comparisons to Fokker
      Planck simulations of hot spot heating, it performs better than previous models.
      The growth rate of thermal filamentation is considerably changed by this thermal
      conductivity modification. First results from a formula describing the isotropic
      component, f(0)(x,v), of the electron velocity distribution function as a spatial
      convolution over local Maxwellians are also presented.

PMID- 12513420
TI  - Fluid modeling of the laser ablation depth as a function of the pulse duration
      for conductors.
AB  - Laser ablation of an aluminum target as a function of the pulse duration, for
      fluences up to 30 J/cm(2) and a wavelength of 0.8 microm, is investigated by
      means of a fluid code. For a given fluence, the ablation depth shows a minimum
      for a pulse duration of approximately 10 ps between a maximum obtained for pulses
      shorter than approximately 1 ps and a lower maximum obtained for pulses in the
      nanosecond range, in qualitative agreement with published experimental results.
      The decrease in ablation depth with increase in pulse duration observed between 1
      and 10 ps results from the reduced temperature rise near the surface due to
      increased inward heat transport. The increase in the ablation depth above
      approximately 10 ps is due to the increase in electron density gradient length
      while the laser pulse intensity is close to maximum, which thus enables the
      plasma to absorb more of the laser pulse energy for increased ablation.

PMID- 12513421
TI  - Subluminous phase velocity of a focused laser beam and vacuum laser acceleration.
AB  - It has been found that for a focused laser beam propagating in free space, there
      exists, surrounding the laser beam axis, a subluminous wave phase velocity
      region. Relativistic electrons injected into this region can be trapped in the
      acceleration phase and remain in phase with the laser field for sufficiently long
      times, thereby receiving considerable energy from the field. Optics placed near
      the laser focus are not necessary, thus allowing high intensities and large
      energy gains. Important features of this process are examined via test particle
      simulations. The resulting energy gains are in agreement with theoretical
      estimates based on acceleration by the axial laser field.

PMID- 12513422
TI  - Generation of single-frequency coherent transition radiation by a prebunched
      electron beam traversing a vacuum beam tunnel in a periodic medium.
AB  - A classical Maxwell equation longitudinal boundary value problem analysis of a
      prebunched ac electron beam traversing a vacuum tunnel in a periodic layered
      dielectric medium is used to calculate the single-frequency coherent transition
      radiation power generated per unit length. For low voltage electron beams in the
      kilovolt range, only transition radiation is produced, the Cerenkov effect being
      below threshold. A numerical example indicates that power levels of the order of
      milliwatts per centimeter can be produced in the 35 GHz range with 3-10 keV
      beams. An interesting aspect of transition versus Cerenkov radiation is that the
      transition "cone" of radiation is in the backward direction of the charge beam.

PMID- 12513423
TI  - Induced modulation instability of partially spatially incoherent light with
      varying perturbation periods.
AB  - We demonstrate experimentally that a periodic perturbation on a partially
      spatially incoherent optical beam induces modulation instability that depends
      strongly on the perturbation periods as well as on the strength of the
      nonlinearity and the degree of spatial coherence. At a fixed value of the
      nonlinearity and coherence, the incoherent modulation instability has a maximum
      growth at a preferred perturbation period (or spatial frequency), leading to the
      formation of ordered patterns. While the nonlinearity in our photorefractive
      system is inherently anisotropic, pattern control and pattern switching with
      anisotropic coherence is readily realized. Our experimental observations are in
      good agreement with theoretical predictions.

PMID- 12513424
TI  - Existence of multibreathers in chains of coupled one-dimensional Hamiltonian
      oscillators.
AB  - We prove the existence of monoparametric families of multibreathers in chains of
      Hamiltonian oscillators of one degree of freedom, with the total energy of the
      chain as a parameter. At the same time we evaluate the neighborhood of the
      initial conditions for these solutions, as well as their stability. For the proof
      we use an idea originally proposed by Poincare. We apply our results to calculate
      families of multibreathers in a chain consisting of coupled Morse oscillators.

PMID- 12513425
TI  - Discrete kink dynamics in hydrogen-bonded chains: the one-component model.
AB  - We study topological solitary waves (kinks and antikinks) in a nonlinear one
      dimensional Klein-Gordon chain with the on-site potential of a double-Morse type.
      This chain is used to describe the collective proton dynamics in quasi-one
      dimensional networks of hydrogen bonds, where the on-site potential plays the
      role of the proton potential in the hydrogen bond. The system supports a rich
      variety of stationary kink solutions with different symmetry properties. We study
      the stability and bifurcation structure of all these stationary kink states. An
      exactly solvable model with a piecewise "parabola-constant" approximation of the
      double-Morse potential is suggested and studied analytically. The dependence of
      the Peierls-Nabarro potential on the system parameters is studied. Discrete
      traveling-wave solutions of a narrow permanent profile are shown to exist,
      depending on the anharmonicity of the Morse potential and the cooperativity of
      the hydrogen bond (the coupling constant of the interaction between nearest
      neighbor protons).

PMID- 12513426
TI  - Hybrid discrete solitons.
AB  - The existence and stability of discrete solitons in waveguide arrays exhibiting a
      linear variation of the effective index and a Kerr nonlinearity is studied. We
      find that the resonant coupling of the conventional discrete soliton to a linear
      Wannier-Stark state does not entail soliton decay. We rather observe the
      formation of a bound state where the Wannier-Stark state gets nonlinearly
      modified. This results in an infinite number of isolated branches of hybrid
      discrete solitons.

PMID- 12513427
TI  - Noether's theorem and Lie symmetries for time-dependent Hamilton-Lagrange
      systems.
AB  - Noether and Lie symmetry analyses based on point transformations that depend on
      time and spatial coordinates will be reviewed for a general class of time
      dependent Hamiltonian systems. The resulting symmetries are expressed in the form
      of generators whose time-dependent coefficients follow as solutions of sets of
      ordinary differential ("auxiliary") equations. The interrelation between the
      Noether and Lie sets of auxiliary equations will be elucidated. The auxiliary
      equations of the Noether approach will be shown to admit invariants for a much
      broader class of potentials, compared to earlier studies. As an example, we work
      out the Noether and Lie symmetries for the time-dependent Kepler system. The
      Runge-Lenz vector of the time-independent Kepler system will be shown to emerge
      as a Noether invariant if we adequately interpret the pertaining auxiliary
      equation. Furthermore, additional nonlocal invariants and symmetries of the
      Kepler system will be isolated by identifying further solutions of the auxiliary
      equations that depend on the explicitly known solution path of the equations of
      motion. Showing that the invariants remain unchanged under the action of
      different symmetry operators, we demonstrate that a unique correlation between a
      symmetry transformation and an invariant does not exist.

PMID- 12513428
TI  - Inverse-problem approach to designing photonic crystals for cavity QED
      experiments.
AB  - Photonic band gap (PBG) materials are attractive for cavity QED experiments
      because they provide extremely small mode volumes and are monolithic,
      integratable structures. As such, PBG cavities are a promising alternative to
      Fabry-Perot resonators. However, the cavity requirements imposed by QED
      experiments, such as the need for high Q (low cavity damping) and small mode
      volumes, present significant design challenges for photonic band gap materials.
      Here, we pose the PBG design problem as a mathematical inversion and provide an
      analytical solution for a two-dimensional (2D) crystal. We then address a planar
      (2D crystal with finite thickness) structure using numerical techniques.

PMID- 12513429
TI  - Path-averaged optical soliton in double-periodic dispersion-managed systems.
AB  - A path-averaged Gabitov-Turitsyn model governing optical signal propagation down
      the dispersion-managed (DM) transmission line is studied numerically. A different
      numerical algorithm to find a soliton solution for an arbitrary periodic DM
      system is proposed. Applying developed technique we analyze soliton solutions for
      few important practical systems.

PMID- 12513430
TI  - Adiabatic theorem and continuous coupled-mode theory for efficient taper
      transitions in photonic crystals.
AB  - We prove that an adiabatic theorem generally holds for slow tapers in photonic
      crystals and other strongly grated waveguides with arbitrary index modulation,
      exactly as in conventional waveguides. This provides a guaranteed pathway to
      efficient and broad-bandwidth couplers with, e.g., uniform waveguides. We show
      that adiabatic transmission can only occur, however, if the operating mode is
      propagating (nonevanescent) and guided at every point in the taper. Moreover, we
      demonstrate how straightforward taper designs in photonic crystals can violate
      these conditions, but that adiabaticity is restored by simple design principles
      involving only the independent band structures of the intermediate gratings. For
      these and other analyses, we develop a generalization of the standard coupled
      mode theory to handle arbitrary nonuniform gratings via an instantaneous Bloch
      mode basis, yielding a continuous set of differential equations for the basis
      coefficients. We show how one can thereby compute semianalytical reflection and
      transmission through crystal tapers of almost any length, using only a single
      pair of modes in the unit cells of uniform gratings. Unlike other numerical
      methods, our technique becomes more accurate as the taper becomes more gradual,
      with no significant increase in the computation time or memory. We also include
      numerical examples comparing to a well-established scattering-matrix method in
      two dimensions.

PMID- 12513431
TI  - Influence of stochasticity on multiple four-wave-mixing processes in an optical
      fiber.
AB  - In this paper, we present the results of a computational study of the dynamical
      evolution of multiple four-wave-mixing processes in a single mode optical fiber
      with spatially and temporally delta-correlated phase noise. A generalized
      nonlinear Schrodinger equation (NLSE) with stochastic phase fluctuations along
      the length of the fiber is solved using the split-step Fourier method. A good
      agreement is obtained with previous experimental and computational results based
      on a truncated-ODE (ordinary differential equation) model, in which stochasticity
      was seen to play a key role in determining the nature of the dynamics. The full
      NLSE allows for simulations with high frequency resolution (60 MHz) and frequency
      span (16 THz) compared to the truncated-ODE model (300 GHz and 2.8 THz,
      respectively), thus enabling a more detailed comparison with observations. A
      physical basis for this hitherto phenomenological phase noise is discussed and
      quantified.

PMID- 12513432
TI  - Composite solitons and two-pulse generation in passively mode-locked lasers
      modeled by the complex quintic Swift-Hohenberg equation.
AB  - The complex quintic Swift-Hohenberg equation (CSHE) is a model for describing
      pulse generation in mode-locked lasers with fast saturable absorbers and a
      complicated spectral response. Using numerical simulations, we study the single-
      and two-soliton solutions of the (1+1)-dimensional complex quintic Swift
      Hohenberg equations. We have found that several types of stationary and moving
      composite solitons of this equation are generally stable and have a wider range
      of existence than for those of the complex quintic Ginzburg-Landau equation. We
      have also found that the CSHE has a wider variety of localized solutions. In
      particular, there are three types of stable soliton pairs with pi and pi/2 phase
      difference and three different fixed separations between the pulses. Different
      types of soliton pairs can be generated by changing the parameter corresponding
      to the nonlinear gain (epsilon).

PMID- 12513433
TI  - Ring dark solitary waves: experiment versus theory.
AB  - Experimental results on optical ring dark solitary wave dynamics are presented,
      emphasizing the interplay between initial dark beam contrast, total phase shift,
      background-beam intensity, and saturation of the nonlinearity. The results are
      found to confirm qualitatively the existing analytical theory and are in
      agreement with the numerical simulations carried out.

PMID- 12513434
TI  - Alternative paradigm for physical computing.
AB  - We identify a different class of physical systems that are able to form universal
      logic gates. By analogy with Si(100) surface dimers, we present a model to
      analyze the trajectories of the fixed points (interpreted as logic states) under
      variation of the basic parameters. Using the perspective of catastrophe theory,
      we show that information processing is the result of cycling the parameters of
      such systems through a path containing a cusp-type catastrophe. We apply this
      analysis to the construction of an example based on magnetic memory.

PMID- 12513435
TI  - Precursor forms of cavity solitons in nonlinear semiconductor microresonators.
AB  - We study the transverse nonlinear dynamics of bulk and multi-quantum well AlGaAs
      microresonators, in the mixed dispersive and saturable absorptive regime,
      slightly below the band-gap edge energy. With a Gaussian beam excitation we
      observe strongly localized states of various shapes, bright or dark in
      reflection. Their dynamics appears to be ruled by strong thermally induced
      nonlinear mechanisms, acting as a dressing mechanism for electronic
      nonlinearities. Precursor forms of cavity solitons are also identified.

PMID- 12513436
TI  - Field statistics of two vectorially superposed wave populations.
AB  - Field statistics of observed waves and radiation constrain the physics of the
      emission process and source region. However, data often contain two or more
      superposed signals or a signal superposed on a noise background, creating
      difficulties for interpretation. Here, the combined probability distribution of
      the field formed by vector superposition of two signals, each with specified
      statistics, is written as a double integral with integrable singularities. The
      analytic result and its numerical solutions for combinations of Gaussian and
      lognormally distributed signals show that these predictions differ from those for
      field or intensity convolution and from the individual wave distributions. At
      high fields, the combined distribution takes the qualitative form of the dominant
      individual distribution (which is localized or otherwise extends to larger
      fields) but develops a significant tail at low fields due to vector superposition
      of almost antiparallel fields with similar magnitudes. It is shown that very
      nearly power-law distributions can develop in significant field domains, despite
      neither component distribution being power law. This is relevant to alternative
      interpretations in terms of self-organized criticality and certain modulational
      wave instabilities. The formalism is then applied to observations of the Vela
      pulsar, resulting in greatly improved fits to data and different interpretations.
      Specifically, the results are strong evidence that stochastic growth theory (SGT)
      is relevant and that the approximate power-law statistics found at some phases
      are not intrinsic but rather due to vector convolution of a Gaussian background
      with a lognormal; the latter is interpretable in terms of SGT. The field
      statistics are consistent with the emission mechanism being a direct linear
      instability or indirect generation via linear mode conversion of nonescaping
      waves driven by a linear instability. They are inconsistent with nonlinear self
      focusing instabilities generating the observed pulsar radiation. This formalism
      and its results should also be widely applicable to other types of wave growth in
      inhomogeneous media.

PMID- 12513437
TI  - Generic features of modulational instability in nonlocal Kerr media.
AB  - The modulational instability (MI) of plane waves in nonlocal Kerr media is
      studied for a general response function. Several generic properties are proven
      mathematically, with emphasis on how new gain bands are formed through a
      bifurcation process when the degree of nonlocality, sigma, passes certain
      bifurcation values and how the bandwidth and maximum of each individual gain band
      depends on sigma. The generic properties of the MI gain spectrum, including the
      bifurcation phenomena, are then demonstrated for the exponential and rectangular
      response functions. For a focusing nonlinearity the nonlocality tends to suppress
      MI, but can never remove it completely, irrespectively of the shape of the
      response function. For a defocusing nonlinearity the stability properties depend
      sensitively on the profile of the response function. For response functions with
      a positive-definite spectrum, such as Gaussians and exponentials, plane waves are
      always stable, whereas response functions with spectra that are not positive
      definite (such as the rectangular) will lead to MI if sigma exceeds a certain
      threshold. For the square response function, in both the focusing and defocusing
      case, we show analytically and numerically how new gain bands that form at higher
      wave numbers when sigma increases will eventually dominate the existing gain
      bands at lower wave numbers and abruptly change the length scale of the periodic
      pattern that may be observed in experiments.

PMID- 12513438
TI  - Minimum description length neural networks for time series prediction.
AB  - Artificial neural networks (ANN) are typically composed of a large number of
      nonlinear functions (neurons) each with several linear and nonlinear parameters
      that are fitted to data through a computationally intensive training process.
      Longer training results in a closer fit to the data, but excessive training will
      lead to overfitting. We propose an alternative scheme that has previously been
      described for radial basis functions (RBF). We show that fundamental differences
      between ANN and RBF make application of this scheme to ANN nontrivial. Under this
      scheme, the training process is replaced by an optimal fitting routine, and
      overfitting is avoided by controlling the number of neurons in the network. We
      show that for time series modeling and prediction, this procedure leads to small
      models (few neurons) that mimic the underlying dynamics of the system well and do
      not overfit the data. We apply this algorithm to several computational and real
      systems including chaotic differential equations, the annual sunspot count, and
      experimental data obtained from a chaotic laser. Our experiments indicate that
      the structural differences between ANN and RBF make ANN particularly well suited
      to modeling chaotic time series data.

PMID- 12513439
TI  - Range-dependent random graphs and their application to modeling large small-world
      Proteome datasets.
AB  - In this paper we consider the problem of characterizing and modeling large-scale
      networks using classes of range-dependent graphs which possess appropriate small
      world properties. The application we have in mind is to bioinformatics, where
      methods of rapid protein identification mean that such proteome datasets, listing
      various observed protein-protein associations, will become more and more
      prevalent. We introduce a class of range-dependent graphs, governed by a power
      law relating intervertex range to edge probability, which are amenable to
      analysis, and for which macroscopic graph parameters are given by explicit forms.
      We show how these may be employed in representing a given network using a maximum
      likelihood approach. This in turn annotates every given edge with its range,
      representing the tendency for such an association to be transitive. We apply this
      technique to published proteome data, and demonstrate that known protein
      associations are thus identified.

PMID- 12513440
TI  - Improved Monte Carlo sampling in a real space approach to the crystallographic
      phase problem.
AB  - A real space approach has been proposed to solve the x-ray phase problem
      formulated as a minimization problem. The cost function consists of two parts:
      one represents the usual crystallographical residual while the other enforces the
      probability distribution of the invariant phase triplets. Starting from a random
      real space structure, the atoms are moved one by one to gradually reduce the cost
      function (simulated annealing). In addition, the atoms are encouragd to
      preferentially sample the high density regions in space determined by an
      approximate density map which in turn is updated and modified by averaging and
      Fourier synthesis. Such a reduction of the configurational space has led to
      considerable improvement of the algorithm compared to an earlier version. Trial
      calculations for structures including hexadecaisoleucinomycin (HEXIL) and a
      collagenlike peptide (PPG) are presented.

PMID- 12513441
TI  - Statistical mechanics of the Bayesian image restoration under spatially
      correlated noise.
AB  - We investigated the use of the Bayesian inference to restore noise-degraded
      images under conditions of spatially correlated noise. The generative statistical
      models used for the original image and the noise were assumed to obey
      multidimensional Gaussian distributions, whose covariance matrices are
      translational invariant. We derived an exact description to be used as the
      expectation for the restored image by the Fourier transformation and restored an
      image distorted by spatially correlated noise by using a spatially uncorrelated
      noise model. We found that the resulting hyperparameter estimations for the
      minimum error and maximal posterior marginal criteria did not coincide when the
      generative probabilistic model and the model used for restoration were in
      different classes, while they did coincide when they were in the same class.

PMID- 12513442
TI  - Transient behavior in single-file systems.
AB  - We have used Monte Carlo methods and analytical techniques to investigate the
      influence of the characteristics, such as pipe length, diffusion, adsorption,
      desorption, and reaction rates on the transient properties of single-file
      systems. The transient or the relaxation regime is the period in which the system
      is evolving to equilibrium. We have studied the system when all the sites are
      reactive and also when only some of them are reactive. Comparisons between mean
      field predictions, cluster approximation predictions, and Monte Carlo simulations
      for the relaxation time of the system are shown. We outline the cases where the
      mean-field analysis gives good results compared to dynamic Monte Carlo results.
      For some specific cases we can analytically derive the relaxation time. Occupancy
      profiles for different distributions of the sites both for the mean field and
      simulations are compared. Different results for slow and fast reaction systems
      and different distributions of reactive sites are discussed.

PMID- 12513443
TI  - Exact and efficient discrete random walk method for time-dependent two
      dimensional environments.
AB  - We present an exact method for speeding up random walk in two-dimensional
      complicated lattice environments. To this end, we derive the discrete two
      dimensional probability distribution function for a diffusing particle starting
      at the center of a square of linear size s. This is used to propagate random
      walkers from the center of the square to sites which are nearest neighbors to its
      perimeter sites, thus saving O(s(2)) steps in numerical simulations. We discuss
      in detail how this method can be implemented efficiently. We examine its
      performance in the diffusion limited aggregation model which produces fractal
      structures, and in a one-sided step-growth model producing compact, fingerlike
      structures. We show that in both cases, the square propagator method reduces the
      computational effort by a factor proportional to the linear system size as
      compared to standard random walk.

PMID- 12513444
TI  - Pinwheel-like structures resulting from interaction of plane pulses of
      excitation.
AB  - We demonstrate that complex spatiotemporal structures may appear in an excitable
      system as the result of interaction between two plane pulses. Such behavior has
      been obtained for FitzHugh-Nagumo type of dynamics by numerical integration of
      reaction-diffusion equations.

PMID- 12513445
TI  - Stationary and nonstationary properties of evolving networks with preferential
      linkage.
AB  - Networks evolving by preferential attachment of both external and internal links
      are investigated. The rate of adding an external link is assumed to depend
      linearly on the degree of a preexisting node to which a new node is connected.
      The process of creating an internal link, between a pair of existing vertices, is
      assumed to be controlled entirely by the vertex that has more links than the
      other vertex in the pair, and the rate of creation of such a link is assumed to
      be, in general, nonlinear in the degree of the more strongly connected vertex. It
      is shown that degree distributions of networks evolving only by creating internal
      links display for large degrees a nonstationary power-law decay with a time
      dependent scaling exponent. Nonstationary power-law behaviors are numerically
      shown to persist even when the number of nodes is not fixed and both external and
      internal connections are introduced, provided that the rate of preferential
      attachment of internal connections is nonlinear. It is argued that nonstationary
      effects are not unlikely in real networks, although these effects may not be
      apparent, especially in networks with a slowly varying mean degree.

PMID- 12513446
TI  - From gene families and genera to incomes and internet file sizes: why power laws
      are so common in nature.
AB  - We present a simple explanation for the occurrence of power-law tails in
      statistical distributions by showing that if stochastic processes with
      exponential growth in expectation are killed (or observed) randomly, the
      distribution of the killed or observed state exhibits power-law behavior in one
      or both tails. This simple mechanism can explain power-law tails in the
      distributions of the sizes of incomes, cities, internet files, biological taxa,
      and in gene family and protein family frequencies.

PMID- 12513447
TI  - Non-normality and the localized control of extended systems.
AB  - The idea of controlling the dynamics of spatially extended systems using a small
      number of localized perturbations is very appealing-such a setup is easy to
      implement in practice. However, when the distance between controllers generating
      the perturbations becomes large, control fails due to extreme sensitivity of the
      system to noise. This sensitivity results from strong non-normality of the
      evolution operator governing the dynamics of disturbances in the controlled
      system. We investigate how non-normality can arise in an originally normal system
      and study how the noise amplification depends on the distance between
      controllers.

PMID- 12513448
TI  - Electrostatic instabilities in current-carrying magnetoplasmas with equilibrium
      density and ion velocity gradients.
AB  - Detailed studies of electrostatic wave instabilities in a current-carrying
      magnetoplasma with equilibrium density and ion velocity gradients are presented.
      For this purpose, a general dispersion relation is derived by using a non
      Boltzmann electron response as well as an ion density perturbation, which
      includes the ion-neutral drag. Our dispersion relation contains previously known
      results as limiting cases, but it also includes some additional instabilities
      associated with the electron-wave resonant interaction. The present results can
      help to understand the origin of the nonthermal electrostatic waves in laboratory
      and space plasmas where there are free energy sources due to ion velocity
      gradients and streaming particle motions.

PMID- 12513449
TI  - Resonant interaction of modulational instability with a periodic soliton in the
      Davey-Stewartson equation.
AB  - The time evolution of the Benjamin-Feir unstable mode in two dimensions is
      studied analytically when it resonates with a periodic soliton. The condition for
      resonance is obtained from an exact solution to the hyperbolic Davey-Stewartson
      equation. It is shown that a growing-and-decaying mode exists only in the
      backward (or forward) region of propagation of the periodic soliton if the
      resonant condition is exactly satisfied. Under a quasiresonant condition, the
      mode grows at first on one side from the periodic soliton, but decays with time.
      The wave field shifts to an intermediate state, where only a periodic soliton in
      a resonant state appears. This intermediate state persists over a comparatively
      long time interval. Subsequently, the mode begins to grow on the other side from
      the periodic soliton.

PMID- 12513450
TI  - Nonlinearity measurements of thin films by third-harmonic-generation microscopy.
AB  - We show that the electronic part of the nonlinear susceptibility chi(3) of thin
      films can be easily measured by third harmonic microscopy. The phenomenon of
      third harmonic generation (THG) is excited by a femtosecond laser beam focused at
      the interface between the thin film and a reference layer. The value of chi(3) is
      deduced from the THG intensity measurements with the help of a classical model.
      The validity of this simple and alternative method is established by testing
      reference liquid films.

PMID- 12513451
TI  - Goos-Hanchen shift in negatively refractive media.
AB  - The Goos-Hanchen shift is calculated when total internal reflection occurs at an
      interface between "normal" and negatively refractive media. The shift is
      negative, consistent with the direction of energy flow in the negatively
      refractive medium.

PMID- 12513452
TI  - Anomalous delay in wave propagation and tunneling: a transition-elements analysis
      of the traversal time.
AB  - An alternative model for near-field propagation and optical tunneling is proposed
      following the lines of the path-integral method developed by Feynman, and in
      particular by using a transition-elements analysis. Such a model was able to
      account for the frequency dependency of delay-time results of an experiment
      involving microwave propagation in the near field using two horn antennas [A.
      Ranfagni et al., Phys. Rev. E 66, 036111 (2002)]. Furthermore, this approach is
      also capable of interpreting delay-time results as a function of the barrier
      width in a frustrated total internal reflection experiment performed at the
      microwave scale and in the optical region.

PMID- 12513453
TI  - 1/f(alpha) noise from correlations between avalanches in self-organized
      criticality.
AB  - We show that large, slowly driven systems can evolve to a self-organized critical
      state where long-range temporal correlations between bursts or avalanches produce
      low-frequency 1/f(alpha) noise. The avalanches can occur instantaneously in the
      external time scale of the slow drive, and their event statistics are described
      by power-law distributions. A specific example of this behavior is provided by
      numerical simulations of a deterministic "sandpile" model, where a scaling
      relation links alpha with the avalanche power-law exponent.

PMID- 12513454
TI  - Kinetics of migration-driven aggregation processes.
AB  - We study the kinetic behavior of the growth of aggregates driven by reversible
      migration between any two aggregates. For the simple system with the migration
      rate kernel K(k;j)=K(')(k;j) proportional, variant kj(upsilon) at which the
      monomers migrate between the aggregates of size k and those of size j, we find
      that for the upsilon< or =2 case the evolution of the system always obeys a
      scaling law. Moreover, the typical aggregate size grows as exp(2IA(0)t) in the
      case of upsilon=2 and as t(1/(2-upsilon)) in the case of -1<upsilon<2. In
      particular, when upsilon< or =-2, the typical aggregate size always grows as
      t(1/3) and the aggregate-size distribution approaches a similar scaling form.

PMID- 12513455
TI  - Ratchet for energy transport between identical reservoirs.
AB  - A one-dimensional periodic array of elastically colliding hard points, with a
      noncentrosymmetric unit cell, connected at its two ends to identical but
      nonthermal energy reservoirs, is shown to carry a sustained unidirectional energy
      current.

PMID- 12513456
TI  - Symmetry breaking and coarsening of clusters in a prototypical driven granular
      gas.
AB  - Granular hydrodynamics predicts symmetry-breaking instability in a two
      dimensional ensemble of nearly elastically colliding smooth hard disks driven, at
      zero gravity, by a rapidly vibrating sidewall. Supercritical and subcritical
      symmetry-breaking bifurcations of the stripe state are identified, and the
      supercritical bifurcation curve is computed. The cluster dynamics proceed as a
      coarsening process mediated by the gas phase. Well above the bifurcation point
      the final steady state, selected by coarsening, represents a single strongly
      localized densely packed "droplet."

PMID- 12513457
TI  - Molecular hydrodynamic theory of supercooled liquids and colloidal suspensions
      under shear.
AB  - We extend the conventional mode-coupling theory of supercooled liquids to systems
      under stationary shear flow. Starting from generalized fluctuating hydrodynamics,
      a nonlinear equation for the intermediate scattering function is constructed. We
      evaluate the solution numerically for a model of a two-dimensional colloidal
      suspension and find that the structural relaxation time decreases as gamma;(-nu)
      with an exponent nu</=1, where gamma; is the shear rate. The results are in
      qualitative agreement with recent molecular dynamics simulations. We discuss the
      physical implications of the results.

PMID- 12513458
TI  - Elasticity of semiflexible polymers.
AB  - We present a method for solving the wormlike chain model for semiflexible
      polymers to any desired accuracy over the entire range of polymer lengths. Our
      results are in excellent agreement with recent computer simulations and reproduce
      important qualitatively interesting features observed in simulations of polymers
      of intermediate lengths. We also make a number of predictions that can be tested
      in a variety of concrete experimental realizations. The expected level of finite
      size fluctuations in force-extension curves is also estimated. This study is
      relevant to mechanical properties of biological molecules.

PMID- 12513459
TI  - Analytic description of stochastic calcium-signaling periodicity.
AB  - Calcium release is an important tool for cellular signaling processes where
      chemical signals are converted into spatio-temporal variations of intracellular
      calcium concentration. We investigated the temporal behavior of a single cluster
      of inositol-(1,4,5)-triphosphate receptor (IP3R)-I channels and will present an
      analytic approach to obtain the spectrum of the calcium signal within the
      cluster. We compare these results with stochastic simulations and obtain an
      intermediate number of channels per cluster for optimal signaling periodicity.

PMID- 12513460
TI  - NMR elastometry of fluid membranes in the mesoscopic regime.
AB  - In solid-state 2H NMR of fluid lipid bilayers, quasielastic deformations at MHz
      frequencies are detected as a square-law dependence of the nuclear spin-lattice
      (R(1Z)) relaxation rates and order parameters (S(CD)). The signature square-law
      slope is found to decrease progressively with the mole fraction of cholesterol
      and with the acyl chain length, due to a stiffening of the membrane. The
      correspondence to thermal vesicle fluctuations and molecular dynamics simulations
      implies that a broad distribution of modes is present, ranging from the membrane
      size down to the molecular dimensions.

PMID- 12513461
TI  - Three and four current reversals versus temperature in correlation ratchets with
      a simple sawtooth potential.
AB  - Transport of Brownian particles in a simple sawtooth potential subjected to both
      unbiased thermal and nonequilibrium symmetric three-level Markovian noise is
      considered. The effects of three and four current reversals as a function of
      temperature are established in such correlation ratchets. The parameter space
      coordinates of the fixed points associated with these current reversals and the
      necessary and sufficient conditions for the existence of the current reversals
      are found.

PMID- 12513462
TI  - Asymptotic analysis of a random walk with a history-dependent step length.
AB  - We study an unbiased, discrete-time random walk on the nonnegative integers, with
      the origin absorbing, and a history-dependent step length. Letting y denote the
      maximum distance the walker has ever been from the origin, steps that do not
      change y have length v, while those that increase y (taking the walker to a site
      that has never been visited) have length n. The process serves as a simplified
      model of spreading in systems with an infinite number of absorbing
      configurations. Asymptotic analysis of the probability generating function shows
      that, for large t, the survival probability decays as S(t) approximately t(
      delta), with delta=v/2n. Our expression for the decay exponent is in agreement
      with the results obtained via numerical iteration of the transition matrix.

PMID- 12513463
TI  - Hopping diffusion of two coupled particles in the random trap model.
AB  - We show that the hopping dynamics of two strongly connected particles can be
      mapped exactly to single particle dynamics. In this way we are able to calculate
      the exact asymptotic diffusion coefficient of two connected particles on a linear
      chain in the random trap model. In particular we calculate the diffusion
      coefficient for exponentially distributed site energies and show that there
      exists a critical temperature below which a subdiffusive behavior appears. It
      turns out that this critical temperature is twice higher than the critical
      temperature in the single particle case [S. Havlin, B. L. Trus, and G. H. Weiss,
      J. Phys. A: Math. Gen. 19, L817 (1986)].

PMID- 12513464
TI  - Crossover effects in a discrete deposition model with Kardar-Parisi-Zhang
      scaling.
AB  - We simulated a growth model in (1+1) dimensions in which particles are aggregated
      according to the rules of ballistic deposition with probability p or according to
      the rules of random deposition with surface relaxation (Family model) with
      probability 1-p. For any p>0, this system is in the Kardar-Parisi-Zhang (KPZ)
      universality class, but it presents a slow crossover from the Edwards-Wilkinson
      class (EW) for small p. From the scaling of the growth velocity, the parameter p
      is connected to the coefficient lambda of the nonlinear term of the KPZ equation,
      giving lambda approximately p(gamma), with gamma=2.1+/-0.2. Our numerical results
      confirm the interface width scaling in the growth regime as W approximately
      lambda(beta)t(beta) and the scaling of the saturation time as tau approximately
      lambda(-1)L(z), with the expected exponents beta=1/3 and z=3/2, and strong
      corrections to scaling for small lambda. This picture is consistent with a
      crossover time from EW to KPZ growth in the form t(c) approximately lambda(-4)
      approximately p(-8), in agreement with scaling theories and renormalization group
      analysis. Some consequences of the slow crossover in this problem are discussed
      and may help investigations of more complex models.

PMID- 12513465
TI  - Quantum Kramers equation for energy diffusion and barrier crossing dynamics in
      the low-friction regime.
AB  - Based on a true phase space probability distribution function and an ensemble
      averaging procedure we have recently developed [Phys. Rev. E 65, 021109 (2002)] a
      non-Markovian quantum Kramers equation to derive the quantum rate coefficient for
      barrier crossing due to thermal activation and tunneling in the intermediate to
      strong friction regime. We complement and extend this approach to weak friction
      regime to derive quantum Kramers equation in energy space and the rate of decay
      from a metastable well. The theory is valid for arbitrary temperature and noise
      correlation. We show that depending on the nature of the potential there may be a
      net reduction of the total quantum rate below its corresponding classical value,
      which is in conformity with earlier observation. The method is independent of
      path integral approaches and takes care of quantum effects to all orders.

PMID- 12513466
TI  - Coupling-reentrant phase transition, complex hysteretic behavior, and efficiency
      optimization in coupled phase oscillators submitted to colored flashing
      potentials.
AB  - A recent mean-field analysis of a model consisting of N nonlinear phase
      oscillators-under the joint influence of global periodic coupling with strength
      K0 and of local multiplicative and additive noises-has shown a nonequilibrium
      phase transition towards a broken-symmetry phase exhibiting noise-induced
      transport, or "ratchet" behavior. In a previous paper we focused on the
      relationship between the character of the (mean velocity <Xdot;> vs load force F)
      hysteresis loop, the number of "homogeneous" mean-field solutions, and the shape
      of the stationary mean-field probability distribution function (PDF). Here we
      assume that the multiplicative noises of the model are Ornstein-Uhlenbeck with
      common strength Q and self-correlation time tau. By resorting to an effective
      Markovian approximation, we study the tau dependence of the phase boundary, and
      that of the line signaling the transition from the "interaction-driven regime" to
      the "noise-driven regime." We also study-for selected representative points of
      the K0 vs Q phase diagram-the tau dependence of the transport properties induced
      by coupling and colored multiplicative noise (including the efficiency epsilon of
      the mechanical rectification process) and that of the above-mentioned PDF.

PMID- 12513467
TI  - Thermodynamics and structure of self-assembled networks.
AB  - We study a generic model of self-assembling chains that can branch and form
      networks with branching points (junctions) of arbitrary functionality. The
      physical realizations include physical gels, wormlike micelles, dipolar fluids,
      and microemulsions. The model maps the partition function of a solution of
      branched, self-assembling, mutually avoiding clusters onto that of a Heisenberg
      magnet in the mathematical limit of zero spin components. As for the calculation
      of thermodynamic properties as well as the scattering structure factor, the
      mapping rigorously accounts for all possible cluster configurations, except for
      closed rings. The model is solved in the mean-field approximation. It is found
      that despite the absence of any specific interaction between the chains, the
      presence of the junctions induces an effective attraction between the monomers,
      which in the case of threefold junctions leads to a first-order reentrant phase
      separation between a dilute phase consisting mainly of single chains, and a dense
      network, or two network phases. The model is then modified to predict the
      structural properties at the mean-field level. Independent of the phase
      separation, we predict a percolation (connectivity) transition at which an
      infinite network is formed. The percolation transition partially overlaps with
      the first-order transition, and is a continuous, nonthermodynamic transition that
      describes a change in the topology of the system. Our treatment that predicts
      both the thermodynamic phase equilibria as well as the spatial correlations in
      the system allows us to treat both the phase separation and the percolation
      threshold within the same framework. The density-density correlation has the
      usual Ornstein-Zernicke form at low monomer densities. At higher densities, a
      peak emerges in the structure factor, signifying the onset of medium-range order
      in the system. Implications of the results for different physical systems are
      discussed.

PMID- 12513468
TI  - Cluster persistence in one-dimensional diffusion-limited cluster-cluster
      aggregation.
AB  - The persistence probability, P(C)(t), of a cluster to remain unaggregated is
      studied in cluster-cluster aggregation, when the diffusion coefficient of a
      cluster depends on its size s as D(s) approximately s(gamma). In the mean field
      the problem maps to the survival of three annihilating random walkers with time
      dependent noise correlations. For gamma> or =0 the motion of persistent clusters
      becomes asymptotically irrelevant and the mean-field theory provides a correct
      description. For gamma<0 the spatial fluctuations remain relevant and the
      persistence probability is overestimated by the random walk theory. The decay of
      persistence determines the small size tail of the cluster size distribution. For
      0<gamma<2 the distribution is flat and, surprisingly, independent of gamma.

PMID- 12513469
TI  - Atomic-scale structure of hard-core fluids under shear flow.
AB  - The effect of velocity correlations on the equal-time density autocorrelation
      function, e.g., the pair distribution function (PDF), of a hard-sphere fluid
      undergoing shear flow is investigated. The PDF at contact is calculated within
      the Enskog approximation and is shown to be in good agreement with molecular
      dynamics simulations for shear rates below the shear-induced ordering transition.
      These calculations are used to construct a nonequilibrium generalized mean
      spherical approximation for the PDF at finite separations, which is also found to
      agree well with the simulation data.

PMID- 12513470
TI  - Random energy model for dynamics in supercooled liquids: N dependence.
AB  - The random energy model (REM) for the critical points (saddles and minima) of the
      potential energy landscape of liquids is further developed. While thermodynamic
      properties may be calculated from the unconditional distribution of states G(E),
      dynamics requires the distribution G(c)(E';E) of energies E' of neighbors
      connected to a state with energy E. Previously it was shown [T. Keyes, Phys. Rev.
      E 62, 7905 (2000)] that an uncorrelated REM, G(c)(E';E)=G(E'), is badly behaved
      in the thermodynamic limit N--> infinity. In the following, a simple expression
      is obtained for G(c)(E';E), which leads to reasonable N dependences. Results are
      obtained for the fraction f(u) of imaginary-frequency instantaneous normal modes,
      the configuration entropy S(c), the distributions of the different-order critical
      points, and the rate R of escape from a state. Simulation data on f(u)(T) and the
      density of minima rho(0)(E) in Lennard-Jones and CS2 are fit with the theory,
      allowing a determination of some model parameters. A universal scaling form for
      f(u), and a consequent scheme for calculating the mode-coupling temperature T(c)
      consistently among different materials, is demonstrated. The dependence of the
      self-diffusion constant D upon R and f(u) is discussed, with the conclusion that
      D proportional, variant f(u) in deeply supercooled states. The phenomenology of
      fragile supercooled liquids is interpreted. It is shown that the REM need not
      have a Kauzmann transition in the relevant temperature range, i.e., above the
      glass transition.

PMID- 12513471
TI  - Brownian motion in dynamically disordered media.
AB  - The motion of Brownian test particles in a model random potential with time
      dependent correlations is investigated using four methods: renormalized
      perturbation, perturbation using Martin, Siggia, and Rose functional formalism
      (MSR), the Edwards variational method on the MSR functional, and renormalization
      group with the MSR function. The disorder averaged one-particle propagators
      determined by the renormalized perturbation expansion and MSR perturbation
      expansion are identical to the second and possibly higher order, and the two
      particle propagators determined by these perturbation methods are identical at
      the first and possibly higher order. The one-particle propagator determined by
      the Edwards method is identical to the perturbation expansions at the first
      order, but the second-order analogue of the Edwards method has a more complex
      expression, which reduces to the second-order perturbation expression with
      additional higher-order terms. The diffusion constant and two-particle
      correlations are calculated from these propagators and are used to determine the
      effects of the random potential on the Brownian particles. Generally, the
      diffusion rate decreases with the disorder strength and increases with the
      temporal decay rate. The two competing mechanisms result in an enhancement of the
      diffusion constant for weak potentials with fast temporal fluctuations. The
      system exhibits two-particle correlations that are inherently non-Gaussian and
      indicate clustering behavior. The diffusion constant is also determined from a
      simple one-loop renormalization group calculation. In the static limit, the
      diffusion constant calculated by the renormalization group recovers the results
      of Deem and Chandler [M.W. Deem and D. Chandler, J. Stat. Phys. 76, 911 (1994)].

PMID- 12513472
TI  - Stationary state in N-body system with power law interaction.
AB  - Many self-gravitating systems often show scaling properties in their mass
      density, system size, velocities, and so on. In order to clarify the origin of
      these scaling properties, we consider the stationary state of N-body system with
      inverse power law interaction. As a simple case, we consider the self-similar
      stationary solution in the collisionless Boltzmann equation with power law
      potential and investigate its stability in terms of a linear symplectic
      perturbation. The stable scaling solutions obtained are characterized by the
      power index of the potential and the virial ratio of the initial state. It is
      suggested in general that the nonextensive system has various stable scaling
      solutions than those in the extensive system.

PMID- 12513473
TI  - Simple model of capillary condensation in cylindrical pores.
AB  - A simple model based on an approximation of the dropletlike model is formulated
      for studying adsorption of fluids into cylindrical pores. This model yields a
      nearly universal description of capillary condensation transitions for noble
      gases confined by alkali metals. The system's thermodynamical behavior is
      predicted from the values of two dimensionless parameters: D* (the reduced
      asymptotic strength of the fluid-adsorber interaction, a function of temperature)
      and R* (the reduced radius of the pore). The phenomenon of hysteresis inherently
      related to capillary condensation is discussed. The connection to a previously
      proposed universality for cylindrical pores is also established.

PMID- 12513474
TI  - Stokes-Einstein-like relation for athermal systems and glasses under shear.
AB  - Finite temperature and athermal simulations are used to determine the viscosity
      mu and diffusivity D for systems undergoing shear flow at shear rate gamma and
      temperature T. Athermal simulations show that mu approximately gamma(-1) and D
      approximately gamma due to strain-activated relaxations, leading to an athermal
      Stokes-Einstein-like relation muD=C(ASE). Finite temperature simulations show
      that at high T the Stokes-Einstein relation muD=C(SE)T is followed, and as T
      decreases muD diverges in the Newtonian limit, but muD reaches the constant value
      C(ASE) for finite gamma. These different behaviors of muD suggest that particle
      dynamics are fundamentally different as jamming is approached by reducing a
      driving force as opposed to cooling, and that dynamic heterogeneities play a
      different role in shear-induced dynamics.

PMID- 12513475
TI  - NMR visualization of displacement correlations for flow in porous media.
AB  - The temporal correlations of velocities for both water and a water-glycerol
      mixture flowing through a random packings of monodisperse spherical particles
      have been investigated using two-dimensional nuclear magnetic resonance methods.
      By combining various flow rates, fluid viscosities, and bead sizes, a wide range
      of flow parameters has been covered, the dimensionless Peclet number ranging from
      100 to 100 000. The velocity exchange spectroscopy (VEXSY) technique has been
      employed to measure the correlation between velocities during two intervals
      separated from each other by a mixing time tau(m). This time is made both large
      and small compared with the time constant tau(c), required for a fluid element
      possessing the average flow velocity to cover a distance equal to the
      characteristic size in the system, the bead diameter. The two-dimensional
      conditional probability of displacement resulting from the VEXSY method reveals
      the existence of different "subensembles" of molecules, including a slow moving
      pool whose displacement is dominated by Brownian motion, an intermediate ensemble
      whose velocities change little over the mixing time, and a fast flowing ensemble
      which loses correlation due to mechanical dispersion. We find that that the
      approach to asymptotic dispersion, as tau(c)/tau(m) increases, depends strongly
      on the Peclet number, the deviation of the velocity autocorrelation function from
      a monoexponential Ornstein-Uhlenbeck process becoming more pronounced with
      increasing Peclet number.

PMID- 12513476
TI  - Wave drag due to generation of capillary-gravity surface waves.
AB  - The onset of the wave resistance via the generation of capillary-gravity waves by
      a small object moving with a velocity V is investigated experimentally. Due to
      the existence of a minimum phase velocity V(c) for surface waves, the problem is
      similar to the generation of rotons in superfluid helium near their minimum. In
      both cases, waves or rotons are produced at V>V(c) due to Cherenkov radiation. We
      find that the transition to the wave drag state is continuous: in the vicinity of
      the bifurcation the wave resistance force is proportional to sqrt[V-V(c)] for
      various fluids. This observation contradicts the theory of Raphael and de Gennes.
      We also find that the reduced wave drag force for different fluids and different
      ball size may be scaled in such a way that all the data collapse on a single
      curve. The capillary-gravity wave pattern and the shape of the wave-generating
      region are investigated both experimentally and theoretically. Good agreement
      between the theory and the experimental data is found in this case.

PMID- 12513477
TI  - Mixing in fully chaotic flows.
AB  - Passive scalar mixing in fully chaotic flows is usually explained in terms of
      Lyapunov exponents, i.e., rates of particle pair separations. We present a
      unified review of this approach (which encapsulates also other nonchaotic flows)
      and investigate its limitations. During the final stage of mixing, when the
      scalar variance decays exponentially, Lyapunov exponents can fail to describe the
      mixing process. The failure occurs when another mixing mechanism, first
      introduced by Fereday et al. [Phys. Rev. E 65, 035301 (2002)], leads to a slower
      decay than the mechanism based on Lyapunov exponents. Here we show that this
      mechanism is governed by the large-scale nonuniformities of the flow which are
      different from the small scale stretching properties of the flow that are
      captured by the Lyapunov exponents. However, during the initial stage of mixing,
      i.e., the stage when most of the scalar variance decays, Lyapunov exponents
      describe well the mixing process. We develop our theory for the incompressible
      and diffusive baker map, a simple example of a chaotic flow. Nevertheless, our
      results should be applicable to all chaotic flows.

PMID- 12513478
TI  - Metastable liquid-liquid phase transition in a single-component system with only
      one crystal phase and no density anomaly.
AB  - We investigate the phase behavior of a single-component system in three
      dimensions with spherically-symmetric, pairwise-additive, soft-core interactions
      with an attractive well at a long distance, a repulsive soft-core shoulder at an
      intermediate distance, and a hard-core repulsion at a short distance, similar to
      potentials used to describe liquid systems such as colloids, protein solutions,
      or liquid metals. We showed [Nature (London) 409, 692 (2001)] that, even with no
      evidence of the density anomaly, the phase diagram has two first-order fluid
      fluid phase transitions, one ending in a gas-low-density-liquid (LDL) critical
      point, and the other in a gas-high-density-liquid (HDL) critical point, with a
      LDL-HDL phase transition at low temperatures. Here we use integral equation
      calculations to explore the three-parameter space of the soft-core potential and
      perform molecular dynamics simulations in the interesting region of parameters.
      For the equilibrium phase diagram, we analyze the structure of the crystal phase
      and find that, within the considered range of densities, the structure is
      independent of the density. Then, we analyze in detail the fluid metastable
      phases and, by explicit thermodynamic calculation in the supercooled phase, we
      show the absence of the density anomaly. We suggest that this absence is related
      to the presence of only one stable crystal structure.

PMID- 12513479
TI  - Shocks in vertically oscillated granular layers.
AB  - We study shock formation in vertically oscillated granular layers, using both
      molecular dynamics simulations and numerical solutions of continuum equations to
      Navier-Stokes order. A flat layer of grains is thrown up from an oscillating
      plate during each oscillation cycle and collides with the plate later in the
      cycle. The collisions produce layer compaction near the plate and a high
      temperature shock front that rapidly propagates upward through the layer. The
      shock is highly time dependent, propagating through the layer in only a quarter
      of the cycle. We compare numerical solutions of the continuum equations to
      molecular dynamics simulations that assume binary, instantaneous collisions
      between frictionless, inelastic hard spheres. The two simulations yield results
      for the shock position, shape, and speed that agree well. An investigation of the
      effect of inelasticity shows that the shock velocity increases continuously with
      decreasing inelasticity; the elastic limit is not singular.

PMID- 12513480
TI  - Transport theory of granular swarms.
AB  - The transport of trace granular gas (swarm) in a carrier granular fluid is
      studied by means of the Boltzmann-Lorentz kinetic equation. Time-dependent
      perturbation theory is used to follow the evolution of the granular swarm from an
      arbitrary initial distribution. A nonhydrodynamic extension of the diffusion
      equation is derived, with transport coefficients that are time dependent and
      implicitly depend on the wave vector. Transport coefficients of any order are
      obtained as velocity moments of the solutions of the corresponding kinetic
      equations derived from the Boltzmann-Lorentz equation. For the special case of
      the initial distribution of swarm particles, transport coefficients are
      identified as time derivatives of the moments of the number density. Finally the
      granular particle transport theory is extended by the introduction of the concept
      of non-particle-conserving collisions.

PMID- 12513481
TI  - Molecular dynamics simulations of vibrated granular gases.
AB  - We present molecular dynamics simulations of monodisperse or bidisperse inelastic
      granular gases driven by vibrating walls, in two dimensions (without gravity).
      Because of the energy injection at the boundaries, a situation often met
      experimentally, density and temperature fields display heterogeneous profiles in
      the direction perpendicular to the walls. A general equation of state for an
      arbitrary mixture of fluidized inelastic hard spheres is derived and successfully
      tested against numerical data. Single-particle velocity distribution functions
      with non-Gaussian features are also obtained, and the influence of various
      parameters (inelasticity coefficients, density, etc.) are analyzed. The validity
      of a recently proposed random restitution coefficient model is assessed through
      the study of projected collisions onto the direction perpendicular to that of
      energy injection. For the binary mixture, the nonequipartition of translational
      kinetic energy is studied and compared both to experimental data and to the case
      of homogeneous energy injection ("stochastic thermostat"). The rescaled velocity
      distribution functions are found to be very similar for both species.

PMID- 12513482
TI  - Driven low density granular mixtures.
AB  - We study the steady state properties of a two-dimensional granular mixture in the
      presence of energy driving by employing simple analytical estimates and direct
      simulation Monte Carlo. We adopt two different driving mechanisms, (a) a
      homogeneous heat bath with friction and (b) a vibrating boundary (thermal or
      harmonic) in the presence of gravity. The main findings are the appearance of two
      different granular temperatures, one for each species; the existence of
      overpopulated tails in the velocity distribution functions and of nontrivial
      spatial correlations indicating the spontaneous formation of cluster aggregates.
      In the case of a fluid subject to gravity and to a vibrating boundary, both
      densities and temperatures display nonuniform profiles along the direction normal
      to the wall, in particular, the temperature profiles are different for the two
      species while the temperature ratio is almost constant with the height. Finally,
      we obtained the velocity distributions at different heights and verified the non
      Gaussianity of the resulting distributions.

PMID- 12513483
TI  - Viscosity bifurcation in granular materials, foams, and emulsions.
AB  - We show that the rheological properties of dry granular materials, as well as
      foams and emulsions, are similar to typical thixotropic fluids: under a
      sufficiently strong shear the viscosity decreases in time, leading to a
      hysteresis in an up-and-down stress ramp. This leads to a viscosity bifurcation
      around a critical stress: for smaller stresses, the viscosity increases in time
      and the material eventually stops flowing, whereas for slightly larger stresses
      the viscosity decreases continuously with time and the flow accelerates. These
      results show that all jammed systems exhibit strong mechanical similarities
      around the transition between a "fluid" and a "solid" state, and that the
      transition between these states is discontinuous. This similarity is further
      emphasized by the fact that both a simple model for the dynamics of a grain on a
      sandpile [Quartier et al., Phys. Rev. E 62, 8299 (2000)] and a simple model for
      the thixotropic behavior of (colloidal) pastes [Coussot et al., Phys. Rev. Lett.
      88, 175501 (2002)] extrapolated to granular flows qualitatively predict this
      viscosity bifurcation.

PMID- 12513484
TI  - Breakdown of self-organized criticality in sandpiles.
AB  - We introduce two sandpile models which show the same behavior of real sandpiles,
      that is, an almost self-organized critical behavior for small systems and a
      dominance of large avalanches as the system size increases. The systems become
      fully self-organized critical, with the critical exponents of the Bak, Tank, and
      Wiesenfeld model [P. Bak, C. Tang, and K. Wiesenfeld, Phys. Rev. Lett. 59, 381
      (1987)] as the system parameters are changed, showing that they can make a bridge
      between the well known theoretical and numerical results and what is observed in
      real experiments.

PMID- 12513485
TI  - Stability of monomer-dimer piles.
AB  - We present an experimental and theoretical study of piles consisting of
      monodisperse spherical grains mixed with a weight fraction nu(d) of dimer grains
      made by the rigid bonding of two such spherical grains. The maximum static angle
      of stability tantheta(c) of the pile increases from 0.45 to 1.1 and the grain
      packing fraction Phi decreases from 0.58 to 0.52 as nu(d) is increased from 0 to
      1. The stability of these piles appears to be controlled by the grains sitting on
      the surface, which roll out of their local "traps" as the tilt angle is
      increased. We attribute the increase in tan theta(c)(nu(d)) to the enhanced
      stability of dimers on the surface, such that at higher tilt angles, there are
      sufficiently many stable surface traps available to accommodate the reduced
      density of monomers on the surface. A full characterization of the grain-scale
      roughness of the surface is required to quantitatively account for the changes in
      theta(c) with nu(d).

PMID- 12513486
TI  - Flory-Huggins theory for athermal mixtures of hard spheres and larger flexible
      polymers.
AB  - A simple analytic theory for mixtures of hard spheres and larger polymers with
      excluded volume interactions is developed. The mixture is shown to exhibit
      extensive immiscibility. For large polymers with strong excluded volume
      interactions, the density of monomers at the critical point for demixing
      decreases as one over the square root of the length of the polymer, while the
      density of spheres tends to a constant. This is very different from the behavior
      of mixtures of hard spheres and ideal polymers, these mixtures, although even
      less miscible than those with polymers with excluded volume interactions, have a
      much higher polymer density at the critical point of demixing. The theory applies
      to the complete range of mixtures of spheres with flexible polymers, from those
      with strong excluded volume interactions to ideal polymers.

PMID- 12513487
TI  - Rearrangements in hard-sphere glasses under oscillatory shear strain.
AB  - We investigate particle rearrangements in colloidal glasses subjected to
      oscillatory shear strain by the technique of light scattering (LS) echo. LS echo
      directly follows the motion of the particles through peaks (echoes) in the
      intensity autocorrelation function; the height of the peak measures the
      reversible motion in the sample. Polydisperse hard-sphere poly-methylmethacrylate
      particles were used to avoid crystallization under shear. The yielding behavior
      is monitored through irreversible particle rearrangements at several volume
      fractions in the glass phase region. At high volume fractions the glasses are
      found to yield at strains as high as 15% while the irreversible rearrangements
      have a more gradual onset with strain for low volume fraction glasses. The
      behavior of high order echoes at long times is related to the effects of shear on
      the frozen-in fluctuations of the glass.

PMID- 12513488
TI  - Simple model for heterogeneous flows of yield stress fluids.
AB  - Various experiments evidence spatial heterogeneities in sheared yield stress
      fluids. To account for heterogeneities in the velocity gradient direction, we use
      a simple model corresponding to a nonmonotonic local flow curve and study a
      simple shear geometry. Different types of boundary conditions are considered.
      Under controlled macroscopic shear stress Sigma, we find homogeneous flow in the
      bulk and a hysteretic macroscopic stress-shear-rate curve. Under controlled
      macroscopic shear rate Gamma;, shear banding is predicted within a range of
      values of Gamma;. For small shear rates, stick-slip can also be observed. These
      qualitative behaviors are robust to changes in the boundary conditions.

PMID- 12513489
TI  - Contribution of physical clusters to phase behavior.
AB  - In a multicomponent fluid mixture, each physical cluster generated as an ensemble
      consisting of particles joined by each particle pair characterized by a bound
      state E(ij)+u(ij)</=0 can contribute towards prohibiting a transition from its
      macroscopically homogeneous phase to its macroscopically inhomogeneous phase.
      Here, E(ij) and u(ij) represent the relative kinetic energy and the pair
      potential for the pair of i and j particles, respectively. Branches constructing
      such physical clusters can confine unbound particles (i.e., particles
      constituting pairs characterized by an unbound state E(ij)+u(ij)>0) within
      regions surrounded by the branches, and can prohibit the boundaries of the
      regions from expanding freely. Particles belonging to one of the two groups
      characterizing constituents of a multicomponent fluid mixture (particles of A)
      should have a tendency to satisfy the condition E(ij)+u(ij)</=0; particles
      belonging to the other group (particles of B) should have a tendency to satisfy
      the condition E(ij)+u(ij)>0. The pair connectedness P(ij)(sigma) proportional to
      the probability that a particle of A is bound near another particle of A hardly
      varies as densities of particles of A increase, although the mean physical
      cluster size diverges to infinity as the densities approach values specified at
      the percolation threshold. Thus, each physical cluster should grow toward that
      having a larger span as densities of particles of A increase. According to this
      growth of physical clusters, the number of unbound particles confined by branches
      of the physical clusters is enhanced. The formation of physical clusters of
      particles of A can be considered as a primary phenomenon resulting in density
      fluctuations. Their formation results in the confinement of particles of B and A
      within regions surrounded by the branches of the physical clusters.

PMID- 12513490
TI  - Nonlinear response of a dipolar system with rotational diffusion to a rotating
      field.
AB  - The rotational diffusion equation for a dipole in the presence of a rotating
      field is solved by expansion of the orientational distribution function in terms
      of spherical harmonics. For the stationary solution, the distribution function
      rotates bodily in angular space. The magnitude of the average dipole moment and
      the lag angle are studied as functions of field strength and frequency. A
      comparison is made with the nonlinear response calculated from approximate
      macroscopic relaxation equations, proposed by Shliomis [Zh. Eksp. Teor. Fiz. 61,
      2611 (1972) [Sov. Phys. JETP 34, 1291 (1972)]] and by Martsenyuk et al. [Zh.
      Eksp. Teor. Fiz. 65, 834 (1973) [Sov. Phys. JETP 38, 413 (1974)]]. Shliomis found
      that for sufficiently high field, the lag angle and the absorption are
      multivalued functions of frequency. This is not the case for the exact solution
      of the rotational diffusion equation presented here. The response of a
      macroscopic system of interacting dipoles is calculated in a mean-field
      approximation for a spherical sample.

PMID- 12513491
TI  - Rotation due to hydrodynamic interactions between two spheres in contact.
AB  - We analyze the rotational and translational motion of two close spheres in a
      fluid at low Reynolds number to investigate if their surfaces come into
      mechanical contact. The rotational motion of a sphere settling close to another
      fixed ball is calculated from a model in which contact interactions between the
      spheres are added to the gravitational and hydrodynamic forces. The model
      predicts a transition from pure rolling to rolling with slip, determined by the
      Coulomb's law, when the ratio of the mechanical friction to the load increases up
      to the static friction coefficient. The dependence of the angular and
      translational velocities on the kinetic friction coefficient and on the
      separation between the particle surfaces is analyzed. The angular and
      translational velocities of a millimeter size bead in a viscous oil, close to a
      fixed bead of a similar size, are measured from video images. Interferometric
      data on translational motion are also collected according to the method
      introduced in our earlier studies. A systematic fitting procedure of the model to
      the experiment is developed and applied to the rotational and translational
      measurements. The model parameters are determined.

PMID- 12513492
TI  - Reconstruction and roughening of a catalytic Pt(110) surface coupled to kinetic
      oscillations.
AB  - Three-dimensional reconstruction and roughening of a Pt(110) surface is studied
      with the help of a qualitative Monte Carlo model. A distinct CO adsorption uptake
      on different surface phases is taken into account. The computations show that a
      "missing row" structure with defects relaxes to a more stable (111)-faceted
      structure. The CO+O2 reaction kinetics is modeled by a phenomenological equation
      with a cubic nonlinearity reproducing a correct qualitative picture of
      oscillations. The surface roughening developing under the reaction conditions
      causes slow changes in catalytic activity of the surface. A nanoscale front
      between the 1x1 and 1x2 phases disintegrates due to repeated phase transitions
      caused by CO coverage oscillations. Defect formation and roughening dominate the
      dynamics of surface phase transitions. A one-dimensional extension of the model
      reproduces microscopic traveling waves on the CO diffusion scale.

PMID- 12513493
TI  - Nucleation rates and induction times during colloidal crystallization: links
      between models and experiments.
AB  - A kinetic model for the evolution of the cluster size distribution during crystal
      nucleation and growth is presented. The model allows one to establish precise
      links between model parameters and experimental measures of nucleation kinetics.
      This approach demonstrates the significance of several processes not accounted
      for in classical nucleation theories. Chief among these is that the driving force
      for crystal nucleation decreases rapidly due to a reduction of the background
      monomer concentration as crystallization progresses, resulting in a reduction of
      nucleation rates. This, coupled with the disparities in the definitions of
      measured and predicted quantities, leads to significant discrepancies between
      predictions of extant models and experimental estimates of nucleation rates.
      Accounting for these effects, calculations of the kinetic model are shown to be
      in good agreement with experimental estimates of nucleation rates, crystal growth
      velocities, and induction times during the crystallization of hard sphere
      colloidal suspensions.

PMID- 12513494
TI  - Interface scaling in a two-dimensional porous medium under combined viscous,
      gravity, and capillary effects.
AB  - We have investigated experimentally the competition between viscous, capillary,
      and gravity forces during drainage in a two-dimensional synthetic porous medium.
      The displacement of a mixture of glycerol and water by air at constant withdrawal
      rate has been studied. The setup can be tilted to tune gravity, and pressure is
      recorded at the outlet of the model. Viscous forces tend to destabilize the
      displacement front into narrow fingers against the stabilizing effect of gravity.
      Subsequently, a viscous instability is observed for sufficiently large withdrawal
      speeds or sufficiently low gravity components on the model. We predict the
      scaling of the front width for stable situations and characterize it
      experimentally through analyses of the invasion front geometry and pressure
      recordings. The front width under stable displacement and the threshold for the
      instability are shown, both experimentally and theoretically, to be controlled by
      a dimensionless number F which is defined as the ratio of the effective fluid
      pressure drop (i.e., average hydrostatic pressure drop minus viscous pressure
      drop) at pore scale to the width of the fluctuations in the threshold capillary
      pressures.

PMID- 12513495
TI  - Dynamics of low anisotropy morphologies in directional solidification.
AB  - We report experimental results on quasi-two-dimensional diffusion limited growth
      in directionally solidified succinonitrile with small amounts of poly(ethylene
      oxide), acetone, or camphor as a solute. Seaweed growth, or dense branching
      morphology, is selected by growing grains close to the [111] plane, where the in
      plane surface tension is nearly isotropic. The observed growth morphologies are
      very sensitive to small anisotropies in surface tension caused by misorientations
      from the [111] plane. Different seaweed morphologies are found, including the
      degenerate, the stabilized, and the strongly tilted seaweeds. The degenerate
      seaweeds show a limited fractal scaling range and, with increased undercooling,
      suggests a transition from "fractal" to "compact" seaweed. Strongly tilted
      seaweeds demonstrate a significant twofold anisotropy. In addition, seaweed
      dendrite transitions are observed in low anisotropy growth.

PMID- 12513496
TI  - Restricted curvature model with suppression of extremal height.
AB  - A discrete growth model with a restricted curvature constraint is investigated by
      measuring both the surface width and the height difference correlation function.
      In our model, where an extremal height is suppressed, the surface width W shows
      the roughness exponent alpha approximately 0.561 and the dynamics exponent z
      approximately 1.69 in one substrate dimension. However the correlation function
      has an unusual scaling behavior and produces different wandering exponent
      alpha(') approximately 1.33 and its dynamic exponent z(') approximately 4. The
      discrepancy is due to the fact that the correlation length increases with a power
      law t(1/z(')) until it reaches the value proportional to Ldelta at time t(s)
      approximately L(z), where L is the system size and delta is the "window exponent"
      satisfying the relation delta=z/z(')=alpha/alpha('). delta is a new exponent to
      characterize the window size of the system.

PMID- 12513497
TI  - Electric-field-induced transition between the anticlinic and the synclinic
      smectic-C surfaces in free-standing films.
AB  - Anticlinic smectic-C surfaces were found experimentally as ground state
      structures in free-standing films made of smectic liquid crystals with no
      anticlinic bulk phases. A mean-field interpretation of this observation is given
      within a discrete phenomenological model of antiferroelectric liquid crystals,
      which additionally considers the enhanced order present at the surfaces of the
      free-standing films. The temperature dependence of the critical electric field
      that drives the transition between the anticlinic and synclinic smectic-C
      surfaces is evaluated, and fair agreement with the experimental data is found.

PMID- 12513498
TI  - Wetting and capillary nematization of binary hard-platelet and hard-rod fluids.
AB  - Density-functional theory is used to investigate the phase behavior of colloidal
      binary hard-platelet and hard-rod fluids near a single hard wall or confined in a
      slit pore. The Zwanzig model, in which the orientations of the particles of
      rectangular shape are restricted to three orthogonal orientations, is analyzed by
      numerical minimization of the grand potential functional. The density and
      orientational profiles as well as the surface contributions to the grand
      potential are determined. The calculations exhibit a wall-induced continuous
      surface transition from uniaxial to biaxial symmetry for the hard-rod fluid.
      Complete wetting of the wall-isotropic liquid interface by a biaxial nematic film
      for rods and a uniaxial nematic film for platelets is found. For the fluids
      confined by two parallel hard walls, we determine a first-order capillary
      nematization transition for large slit widths, which terminates in a capillary
      critical point upon decreasing the slit width.

PMID- 12513499
TI  - Three-dimensional director structures of defects in Grandjean-Cano wedges of
      cholesteric liquid crystals studied by fluorescence confocal polarizing
      microscopy.
AB  - We use a nondestructive technique of fluorescence confocal polarizing microscopy
      to visualize three-dimensional director patterns of defects in Grandjean-Cano
      wedges filled with a cholesteric liquid crystal of pitch p=5 microm. Strong
      surface anchoring of the director causes a stable lattice of dislocations in the
      bulk. Optical slicing in the vertical cross sections of the wedges allows us to
      establish the detailed structure of dislocations and their kinks. Dislocations of
      Burgers vector b=p/2 are located in the thin part of the sample, very close to
      the bisector plane. Their cores are split into a pair of tau(-1/2) and
      lambda(+1/2) disclinations. Pairs of lambda(-1/2) and tau(+1/2) disclinations are
      observed when the b=p/2 dislocation forms a kink. The kinks along the b=p/2
      dislocations change the level of dislocations by +/-p/4 and +/-p/2; these kinks
      are confined to the glide plane and are very long, (5-10) p. Above some critical
      thickness h(c) of the wedge sample, the dislocations are of Burgers vector b=p.
      They are often found away from the bisector plane. The core of b=p dislocations
      is split into a pair of nonsingular lambda(-1/2) and lambda(+1/2) disclinations.
      The kinks along the b=p dislocation are of a typical size p and form cusps in the
      direction perpendicular to the glide plane. At the cusp, lambda(-1/2) and
      lambda(+1/2) disclinations interchange ends. Other defect structures inlude
      "Lehmann clusters," i.e., dislocations of zero Burgers vector formed by two
      lambda(-1/2) and two lambda(+1/2) disclinations and dislocations of nonzero
      Burgers vector with a core split into more than two disclinations. We employ the
      coarse-grained Lubensky-de Gennes model of the cholesteric phase to describe some
      of the observed features. We calculate the elastic energy of a dislocation away
      from the core, estimate the energy of the core split into disclinations of
      different types, study the effect of finite sample thickness on the dislocations
      energy, and calculate the Peach-Koehler elastic forces that occur when a
      dislocation is shifted from its equilibrium position. Balance of the
      dilation/compression energy in the wedge and the energy of dislocations defines
      the value of h(c) and allows to estimate the core energy of the dislocations.
      Finally, we consider the Peierls-Nabarro mechanisms hindering glide of
      dislocations across the cholesteric layers. Because of the split disclination
      character of the core, glide is difficult as compared to climb, especially for
      b=p dislocations.

PMID- 12513500
TI  - Antiferroelectric liquid-crystal mixture without smectic layer shrinkage at the
      direct Sm-A*-Sm-C(*)(a) transition.
AB  - We report results of x-ray, optic, electro-optic, and dielectric investigations
      on an antiferroelectric liquid-crystal mixture exhibiting a direct second-order
      phase transition between the Sm-A* and Sm-C(*)(a) phases with virtually no
      shrinkage in the smectic layer spacing. The birefringence measurements and
      texture observations suggest that the phase transition follows the diffuse cone
      model of Adrian de Vries, which explains the constant layer spacing. The
      antiferroelectric nature of the tilted phase is verified by the presence of twin
      polarization reversal peaks in the current response and by the absence of strong
      absorptions in the dielectric spectrum. The threshold for switching this phase to
      the synclinic, ferroelectric state is sharp and occurs at a very low voltage.

PMID- 12513501
TI  - Coarsening dynamics of biaxial nematic liquid crystals.
AB  - We study the coarsening dynamics of two- and three-dimensional biaxial nematic
      liquid crystals, using Langevin dynamics. Unlike previous work, we use a model
      with no a priori relationship among the three elastic constants associated with
      director deformations. Biaxial nematics possess four topologically distinct
      classes of defects, three of which have half-integer charge, while the fourth,
      which plays a minor role in coarsening, is of integer charge. We find a rich
      variety of coarsening behavior, including the presence of one, two, or three of
      the half-integer classes at late times, depending on the relative values of the
      elastic constants and the resulting energetics of the decay channels of the
      defects. The morphology of the defect tangle in three dimensions when all three
      classes are present is particularly interesting. Rather than forming independent
      defect loops (as occurs when only one or two of the classes are present), the
      defect lines meet at junction points which are distributed uniformly throughout
      the system. As the system coarsens some pairs of neighboring junction points
      approach each other and annihilate, allowing the formation of nonintersecting
      loops each formed from a single defect class. These loops then shrink
      independently during the very final stages of the coarsening sequence.

PMID- 12513502
TI  - Intermediate periodic "saddle-splay" nematic phase in the vicinity of a nematic
      smectic-A transition.
AB  - We consider possible spontaneous modulations of the nematic director induced by
      the elastic saddle-splay K24 term when the value of the elastic constant K24 does
      not satisfy the Ericksen stability condition for the homogeneous ground state.
      According to the standard formula expressing K24 in terms of the twist elastic
      constant K22, this can be expected close to the nematic-smectic-A transition
      where K22 becomes very large. It is predicted that in a planar nematic layer (or,
      more generally, if the surface director alignment is sufficiently close to a
      planar one), a modulated phase with observable long wavelength period can occur
      in samples considerably thicker than the anchoring extrapolation length. The
      modulated nematic phase is expected to persist into the smectic phase so that its
      temperature of the transition to smectic phase has to be lower than that for the
      homogeneous nematic liquid crystal. Low amplitude short wavelength modulations
      are predicted for any thickness if the surface director is sufficiently far from
      a pure homeotropic alignment. At the expense of this mode the temperature of a
      nematic-smectic-A transition in a planar cell with isotropic surfaces has to be
      lower than that for a homeotropic cell even if the periodic structure is not
      accessible for the direct observation.

PMID- 12513503
TI  - Effect of mosaicity in x-ray studies of critical behavior at the nematic to
      smectic-A transition.
AB  - Previous studies of critical behavior at the nematic to smectic-A transition by
      high-resolution x-ray scattering were performed using low magnetic fields of 0.1
      0.8 T. In those studies, the transverse resolution was limited by the sample
      mosaicity which complicated data analysis. In order to understand the effect of
      sample mosaicity on the measured values of critical exponents, the divergence of
      the smectic order correlation lengths xi(||, perpendicular ) and susceptibility
      sigma(o) was studied in a magnetic field ranging from 0.25 to 5 T. The use of
      high (5 T) field reduced the sample mosaicity and improved the effective
      transverse resolution by almost two orders of magnitude. Three liquid crystals,
      two mixtures of 6th and 7th homologs of 4,4(')-dialkylazoxybenzene (DnAOB) and 4
      n-octylcyanobiphenyl (8CB) were studied. 15 wt% (D6.15AOB) and 40 wt% (D6.4AOB)
      mixtures of D7AOB in D6AOB have a wide nematic range, while 8CB has a narrow
      nematic range. Analysis of the data at different fields revealed a different and
      proper way to apply the mosaicity correction. The Gaussian mosaicity correction
      was found to be temperature independent but significantly ( approximately 3.5
      times) smaller than the width of the sharpest q( perpendicular )-scan, which has
      traditionally been used for mosaicity correction in all previous studies. The
      values of the critical exponents measured over almost four decades of reduced
      temperature were: nu(||)=0.79+/-0.02, nu( perpendicular )=0.69+/-0.02,
      gamma=1.46+/-0.04 for D6.15AOB; nu(||)=0.79+/-0.02, nu( perpendicular )=0.67+/
      0.02, gamma=1.44+/-0.04 for D6.4AOB; and nu(||)=0.70+/-0.02, nu( perpendicular
      )=0.52+/-0.02, gamma=1.24+/-0.04 for 8CB. The results for the two mixtures
      suggest that in wide temperature range nematics, far from the tricritical point,
      the exponents may be material independent. No significant effects of mosaicity on
      the values of the coefficient c of the fourth-order term in the structure factor
      were observed.

PMID- 12513504
TI  - Acoustic realignment of nematic liquid crystals.
AB  - In a nematic liquid-crystal cell, the molecules can be realigned by an ultrasonic
      wave, leading to a change in the optical transmission through the cell. We
      present a model for this acousto-optic effect, and show that the magnitude of
      this effect is controlled by a director-density coupling. We then measure the
      optical transmission as a function of acoustic intensity for three liquid-crystal
      materials, and confirm that the data fit the functional form of the theoretical
      prediction. This fit gives the value of the director-density coupling, which
      varies greatly from material to material.

PMID- 12513505
TI  - Surface effects in nucleation and growth of smectic-B crystals in thin samples.
AB  - We present an experimental study of the surface effects (interactions with the
      container walls) during the nucleation and growth of smectic-B (SmB) crystals
      from the nematic in free growth and directional solidification of a mesogenic
      molecule [C4H9-(C6H10)2CN] called CCH4 in thin (of thickness in the 10-microm
      range) samples. We follow the dynamics of the system in real time with a
      polarizing microscope. The inner surfaces of the glass-plate samples are coated
      with polymeric films, either rubbed polyimid (PI) films or mono-oriented
      poly(tetrafluoroethylene) (PTFE) films deposited by friction at high temperature.
      The orientation of the nematic and the smectic-B is planar. In PI-coated samples,
      the orientation effect of SmB crystals is mediated by the nematic, whereas, in
      PTFE-coated samples, it results from a homoepitaxy phenomenon occurring for two
      degenerate orientations. A recrystallization phenomenon partly destroys the
      initial distribution of crystal orientations. In directional solidification of
      polycrystals in PTFE-coated samples, a particular dynamics of faceted grain
      boundary grooves is at the origin of a dynamical mechanism of grain selection.
      Surface effects also are responsible for the nucleation of misoriented terraces
      on facets and the generation of lattice defects in the solid.

PMID- 12513506
TI  - Length and speed selection in dendritic growth of electrohydrodynamic convection
      in a nematic liquid crystal.
AB  - We present results on dendritic growth of electrohydrodynamic convection in a
      nematic liquid crystal subject to parallel magnetic and electric fields. Previous
      work found that these dendrites have many properties in common with crystalline
      dendrites. Nevertheless, crystalline dendrites are significantly different from
      the system studied here. Specifically, the length selection mechanism for these
      dendrites is substantially richer than that which controls crystalline dendritic
      growth. In contrast with the sharp selection mechanism operating in the case of
      crystalline dendrites, these dendrites show only partial selection. As the
      separation between electrodes and the magnetic field becomes larger, the
      selection becomes even less sharp. We quantify the selection by measuring two
      important characteristics of these dendrites, their length scale, as reflected by
      the tip radius of curvature, and their growth speed. We measure these quantities
      as functions of the most important control parameters: the spacing of the liquid
      crystal cell, the magnetic field, and the applied voltage. A nontrivial scaling
      relationship is found for the tip radius of curvature. These dendrites occur in a
      system containing only one state of matter, and they are defined not by an abrupt
      boundary but by a diffuse interface. We find that the width of that interface is
      determined solely by the applied magnetic field.

PMID- 12513507
TI  - Interaction of particles in a deformed nematic liquid crystal.
AB  - We investigate how the interaction of particles mediated by an elastic
      deformation of a nematic liquid crystal is influenced by the initial deformation
      of the director field. To this end, we calculate the interaction energy between
      particles in a nematic cell with hybrid boundary conditions, homeotropic on the
      surface of one confining plate and planar on the other. We find an analytic form
      of the interaction energy in the case of weak anchoring on the surface of the
      particle. This interaction energy sensitively depends on the position of the two
      particles as well as the interparticle distance and can be nonmonotonic with a
      minimum in its landscape. This nontrivial energy landscape might lead to a
      chainlike superstructure of particles.

PMID- 12513508
TI  - Full energy expression of a uniaxial nematic phase with spatially dependent
      density and order parameters: From microscopic to macroscopic theory.
AB  - We present a microscopic derivation of the full macroscopic energy expression of
      a spatially bounded uniaxial nematic phase. The surface is described by spatial
      variations of the density and scalar order parameters of all even orders. The
      method developed in the paper allowed us to unambiguously separate the surface
      elastic K24 and K13 terms and isotropic and anisotropic surface tension
      (anchoring). The full energy expression incorporating variations of the director,
      scalar order parameters, and density is obtained. The macroscopic coefficients
      are derived in terms of the isotropic and anisotropic fractions of the
      microscopic intermolecular interaction. An important physical consequence of the
      obtained formulas, in particular, is that the observed considerable difference
      K33-K11 between the bend and splay elastic constants unambiguously indicates that
      (i) the intermolecular interaction has a large anisotropic fraction, and thus,
      the effective constant K13 and intrinsic anchoring are considerable; (ii) at
      least some scalar order parameters of order four and higher are essentially
      nonzero. Relation of the developed theory with the Nehring-Saupe theory and
      Landau-de Gennes approach is considered.

PMID- 12513509
TI  - Electroconvection in nematic liquid crystals with positive dielectric and
      negative conductivity anisotropy.
AB  - Electroconvection in an unusual nematic compound with strongly positive
      dielectric anisotropy and negative anisotropy of the conductivity is
      investigated. For homeotropic alignment, where one has a direct transition to
      rolls or squares depending on the frequency of the applied voltage, we present a
      quantitative theory. From the comparison we infer values for some viscosities,
      which are rather unusual, but not unreasonable in view of the vicinity of the
      nematic-smectic transition. For planar alignment, electroconvection sets in above
      a splay Freedericksz transition with "parallel rolls," which is also captured by
      the theory.

PMID- 12513510
TI  - First-order wetting transition at finite contact angle.
AB  - The wetting of a polymer brush by a melt of similar chains can have a window of
      complete wetting with a classical allophobic wetting transition at low grafting
      density sigma and an autophobic one at high sigma. However, when the melt chains
      are much longer than the brush chains, the contact angle alpha goes through a
      nonzero minimum where partial differential alpha/ partial differential sigma has
      a jump. A self-consistent-field analysis and experimental observations indicate a
      double-well disjoining pressure curve, consistent with a first-order wetting
      transition at finite alpha. The metastable contact angle can become zero.

PMID- 12513511
TI  - Conformational instability of rodlike polyelectrolytes due to counterion
      fluctuations.
AB  - The effective elasticity of highly charged stiff polyelectrolytes is studied in
      the presence of counterions, with and without added salt. The rigid polymer
      conformations may become unstable due to an effective attraction induced by
      counterion density fluctuations. Instabilities at the longest, or intermediate
      length scales, may signal collapse to globule, or necklace states, respectively.
      In the presence of added salt, a generalized electrostatic persistence length is
      obtained, which has a nontrivial dependence on the Debye screening length. It is
      also found that the onset of conformational instability is a reentrant phenomenon
      as a function of polyelectrolyte length for the unscreened case, and the Debye
      length or salt concentration for the screened case. This may be relevant in
      understanding the experimentally observed reentrant condensation of DNA.

PMID- 12513512
TI  - Structural modifications in the swelling of inhomogeneous microgels by light and
      neutron scattering.
AB  - Small-angle neutron scattering and dynamic light scattering have been used to
      study the thermodynamics of swelling and the associated structure modifications
      of highly cross-linked temperature-sensitive poly (N-isopropylacrylamide)
      [poly(NIPAM)] microgels in D2O. A particle core-shell model is proposed, with the
      core containing most of the cross-linker molecules. The Flory-Rehner theory, with
      the inclusion of a concentration dependent Flory solvency parameter, successfully
      describes the experimental swelling, despite the inhomogeneous character of the
      particles. Interestingly, the shell evolution with temperature controls the whole
      particle swelling, exerting an external pressure over the core, which in turn
      influences its size during the swelling process. Scaling laws for the correlation
      lengths were found with respect to temperature and polymer concentration.
      Finally, it has been encountered that for the collapsed microgel states, the
      particle surface seems to have a fractal character.

PMID- 12513513
TI  - Kinetic arrest of crowded soft spheres in solvents of varying quality.
AB  - Crowded solutions of multiarm star polymers, representing model colloidal spheres
      with ultrasoft repulsive interactions, undergo a reversible gelation transition
      upon heating in solvents of intermediate quality (between good and Theta). This
      unusual phenomenon is due to the kinetic arrest of the swollen interpenetrating
      spheres at high temperatures, forming clusters, in analogy to the colloidal glass
      transition. In this work we demonstrate that the choice of the solvent has a
      dramatic effect on the gelation transition, because of the different degree of
      star swelling (at the same temperature) associated with the solvent quality. We
      construct a generic kinetic phase diagram for the gelation of different stars in
      different solvents (gelation temperature against effective volume fraction, phi)
      and propose a critical "soft sphere close packing" volume fraction phi(c)
      distinguishing the temperature-induced (for phi<phi(c)) from the concentration
      induced (for phi>phi(c)) glass-like gelation. We conclude that appropriate
      selection of the solvent allows for manipulation of the sol-gel transition in
      such ultrasoft colloids.

PMID- 12513514
TI  - Scattering from supramacromolecular structures.
AB  - We study theoretically the scattering imprint of a number of branched
      supramacromolecular architectures, namely, polydisperse stars and dendrimeric,
      hyperbranched structures. We show that polydispersity and nature of branching
      highly influence the intermediate wave vector region of the scattering structure
      factor, thus providing insight into the morphology of different aggregates formed
      in polymer solutions.

PMID- 12513515
TI  - Effects of nonuniform segment deformation on the constitutive relation of
      polymeric solids.
AB  - A polymeric solid is modeled as a network of beads and strings. Beads in the
      polymer are divided into bead groups represented by the segment end points. Based
      on the equation of motion for each bead in the system, a macroscopic equation of
      motion for the polymer is derived. Velocity fluctuations of beads result in a
      pressure, the isotropic component of the stress, in the polymer. Interaction
      forces transmitted through segments connected to bead groups are the major source
      of the stress in the polymer. The tendency of segments to achieve their minima in
      Helmholtz free energy results in thermal elasticity of the polymer. Compared to
      the time scale of these segment interactions, other interactions among beads
      groups are short in time, therefore, result in a viscous stress. The motion of an
      average segment is modeled as an elastic spring immersed in a viscous fluid. The
      inertia of the segment is neglected because the viscous force is much larger than
      the inertial force. The governing equation for the deformation of the average
      segment is found to be a diffusion equation representing the balance between the
      viscous force and the elastic force in the segment. If the time scale of the
      macroscopic deformation is short compared to that of the deformation diffusion,
      the application of forces at both ends results in nonuniform deformation of the
      segment, which diffuses from the ends toward the center. This diffusion leads to
      relaxation of the macroscopic stress which we represent by a history integral.
      The kernel in the integral is asymptotic to 1/sqrt[t] for a short time t, and is
      asymptotic to an exponentially decaying function for a long time t, in which t is
      the elapsed time from initiation of the deformation. This theoretically predicted
      kernel is observed in experiments conducted at constant temperature.

PMID- 12513516
TI  - Dissolution of a polyelectrolyte-macroion complex by addition of salt.
AB  - The dissolution of complexes formed by a linear polyelectrolyte and oppositely
      charged macroions by addition of salt has been examined by employing a simple
      model with focus on the electrostatic interactions and solved by Monte Carlo
      simulations. In the absence of salt an overcharged complex appears. Upon addition
      of salt, the number of complexed macroions is continuously decreasing, the effect
      being similar for flexible and stiff polyelectrolytes. Regarding the flexible
      polyelectrolyte, the number of polyelectrolyte-macroion contacts is reduced,
      whereas it remains nearly constant for the stiff polyelectrolyte as the salt
      content is increased. A screened Coulomb potential of the Debye-Huckel type, in
      which the small ions are only indirectly described, displays a good
      representation of the system.

PMID- 12513517
TI  - Growth patterns of microscopic brain tumors.
AB  - Highly malignant brain tumors such as glioblastoma multiforme form complex growth
      patterns in vitro in which invasive cells organize in tenuous branches. Here, we
      formulate a chemotaxis model for this sort of growth. A key element controlling
      the pattern is homotype attraction, i.e., the tendency for invasive cells to
      follow pathways previously explored. We investigate this in two ways: we show
      that there is an intrinsic instability in the model, which leads to branch
      formation. We also give a discrete description for the expansion of the invasive
      zone, and a continuum model for the nutrient supply. The results indicate that
      both strong heterotype chemotaxis and strong homotype chemoattraction are
      required for branch formation within the invasive zone. Our model thus can give a
      way to assess the importance of the various processes, and a way to explore and
      analyze transitions between different growth regimes.

PMID- 12513518
TI  - Effects of macromolecular crowding on protein folding and aggregation studied by
      density functional theory: dynamics.
AB  - Inside the living cell is inherently crowded with proteins and other
      macromolecules. Thus, it is indispensable to take into account various
      interactions between the protein and other macromolecules for thorough
      understanding of protein functions in cellular contexts. Here we focus on the
      excluded volume interaction imposed on the protein by surrounding macromolecules
      or "crowding agents." We have presented a theoretical framework for describing
      equilibrium properties of proteins in crowded solutions [A. R. Kinjo and S.
      Takada, Phys. Rev. E (to be published)]. In the present paper, we extend the
      theory to describe nonequilibrium properties of proteins in crowded solutions.
      Dynamics simulations exhibit qualitatively different morphologies depending on
      the aggregating conditions, and it was found that macromolecular crowding
      accelerates the onset of aggregation while stabilizing the native protein in the
      quasiuniform phase before the onset of aggregation. It is also observed, however,
      that the aggregation may be kinetically inhibited in highly crowded conditions.
      The effects of crowding on folding and unfolding of proteins are also examined,
      and the results suggest that fast folding is an important factor in preventing
      aggregation of denatured proteins.

PMID- 12513519
TI  - Binless strategies for estimation of information from neural data.
AB  - We present an approach to estimate information carried by experimentally observed
      neural spike trains elicited by known stimuli. This approach makes use of an
      embedding of the observed spike trains into a set of vector spaces, and entropy
      estimates based on the nearest-neighbor Euclidean distances within these vector
      spaces [L. F. Kozachenko and N. N. Leonenko, Probl. Peredachi Inf. 23, 9 (1987)].
      Using numerical examples, we show that this approach can be dramatically more
      efficient than standard bin-based approaches such as the "direct" method [S. P.
      Strong, R. Koberle, R. R. de Ruyter van Steveninck, and W. Bialek, Phys. Rev.
      Lett. 80, 197 (1998)] for amounts of data typically available from laboratory
      experiments.

PMID- 12513520
TI  - Iron normal mode dynamics in a porphyrin-imidazole model for deoxyheme proteins.
AB  - Iron vibrational modes of a deoxyheme protein model (2
      methylimidazole)(tetraphenylporphinato)iron(II), [Fe(TPP)(2-MeImH)], have been
      studied by refining normal mode calculations to nuclear resonance vibrational
      spectroscopy (NRVS) data. The NRVS measurements give quantitative frequencies and
      iron amplitudes of all modes with significant Fe vibrational motion. Modes with
      in-plane displacement of iron are distinguished from those involving out-of-plane
      motion by measurements on oriented single-crystal samples. Normal modes having
      large overlaps with in-plane nu(42), nu(50), and nu(53) modes of the porphyrin
      core are identified, as well as several modes with large iron-imidazole stretch
      components. An out-of-plane mode at 78 cm(-1) shows significant doming of the
      porphyrin core, but the largest Fe doming motion arises from the coupling of
      phenyls and imidazole at 25 cm(-1).

PMID- 12513521
TI  - Temperature dependence of formation of a supported phospholipid bilayer from
      vesicles on SiO2.
AB  - Adsorption of egg-phosphatidylcholine vesicles and bilayer formation on a SiO2
      surface was investigated in the temperature range 278-303 K using the quartz
      crystal microbalance-dissipation technique. The critical coverage for the vesicle
      ->bilayer transition is found to decrease with increasing temperature. The
      temperature dependence of the time-scale characterizing this transition can be
      represented in the Arrhenius form. Higher temperatures produce a bilayer with
      fewer trapped, nonruptured vesicles.

PMID- 12513522
TI  - Origin of the pattern of trabecular bone: an experiment and a model.
AB  - As a result of an experiment in which the development of a mineral phase in the
      rabbit embryo was observed, a model is proposed to explain the mechanism that
      controls the place of precipitation of crystals in mineralizing tissue. The
      reaction-diffusion equations for the specified compounds are formulated and
      solved. Among a variety of compounds the concentrations of carbon dioxide,
      oxygen, HCO-3 ions, H+ ions, calcium, and inorganic phosphorus are evaluated.
      CO2, HCO-3 ions, and H+ ions, are distinguished due to their key role in the
      maintenance of the pH value. The local concentration of oxygen is the pivot
      factor that controls the metabolic rate, i.e., production of CO2. Next the
      supersaturation was estimated on the basis of the calculated values of pH and the
      concentrations of calcium and inorganic phosphorus. It is assumed that the
      synthesis of the organic matrix breaks the metastable equilibrium with respect to
      spontaneous precipitation and leads to the deposition of minerals. It was found
      that the geometry of the vasculature determines the shape of primitive trabecular
      bone (woven bone) while the value of the diffusion coefficient may be the key
      factor indicating the possibility of mineralization under the control of a living
      organism.

PMID- 12513523
TI  - Unsteady two-dimensional theory of a flapping wing.
AB  - An analytical evaluation of the hydrodynamic force on a single flapping wing is
      presented, based on the two-dimensional inviscid theory, with the addition of an
      attached leading-edge vortex. The explicit expression of the force is given and
      compared with some of the measurements by Dickinson et al. [Science 284, 1954
      (1999)] and Sane and Dickinson [J. Expl. Biol. 204, 2607 (2001)] for a fruit fly
      model wing.

PMID- 12513524
TI  - Stochastic neural network model for spontaneous bursting in hippocampal slices.
AB  - A biologically plausible, stochastic, neural network model that exhibits
      spontaneous transitions between a low-activity (normal) state and a high-activity
      (epileptic) state is studied by computer simulation. Brief excursions of the
      network to the high-activity state lead to spontaneous population bursting
      similar to the behavior observed in hippocampal slices bathed in a high-potassium
      medium. Although the variability of interburst intervals in this model is due to
      stochasticity, first return maps of successive interburst intervals show
      trajectories that resemble the behavior expected near unstable periodic orbits
      (UPOs) of systems exhibiting deterministic chaos. Simulations of the effects of
      the application of chaos control, periodic pacing, and anticontrol to the network
      model yield results that are qualitatively similar to those obtained in
      experiments on hippocampal slices. Estimation of the statistical significance of
      UPOs through surrogate data analysis also leads to results that resemble those of
      similar analysis of data obtained from slice experiments and human epileptic
      activity. These results suggest that spontaneous population bursting in
      hippocampal slices may be a manifestation of stochastic bistable dynamics, rather
      than of deterministic chaos. Our results also question the reliability of some of
      the recently proposed, UPO-based, statistical methods for detecting determinism
      and chaos in experimental time-series data.

PMID- 12513525
TI  - Regions of cardiorespiratory synchronization in humans under paced respiration.
AB  - Cardiorespiratory synchronization under paced respiration is studied
      systematically as the respiration frequency is changed between 3 and 30 breaths
      per min. We plot a one-dimensional cut of the classical picture of
      synchronization regions along the line defining the current breathing amplitude.
      The existence of n:m synchronization regions of finite width is demonstrated for
      each of six subjects studied. The statistics of the different types of
      synchronization and their stability are discussed.

PMID- 12513526
TI  - Physical model for the gating mechanism of ionic channels.
AB  - We propose a physical model for the gating mechanism of ionic channels. First, we
      investigate the fluctuation-mediated interactions between two proteins imbedded
      in a cellular membrane and find that the interaction depends on their
      orientational configuration as well as the distance between them. The
      orientational dependence of interactions arises from the fact that the
      noncircular cross-sectional shapes of individual proteins constrain fluctuations
      of the membrane differently according to their orientational configuration. Then,
      we apply these interactions to ionic channels composed of four, five, and six
      proteins. As the gating stimulus creates the changes in the structural shape of
      proteins composing ionic channels, the orientational configuration of the ionic
      channels changes due to the free energy minimization, and ionic channels are open
      or closed according to the conformation thereof.

PMID- 12513527
TI  - Langevin dynamics of proteins at constant pH.
AB  - An application of the Langevin dynamics algorithm for simulation of protein
      conformational equilibria at constant pH is presented. The algorithm is used to
      compute average protonation of titratable groups in ovomucoid third domain, as
      functions of pH, resulting in data, basically equivalent to the pH dependencies
      of chemical shifts obtained from multidimensional nuclear magnetic resonance
      (NMR) spectroscopy, for the protein titratable residues. The pK(a) values
      obtained from the simulation are in reasonable agreement with experimental data.
      Possible improvements of this methodology, using achievements from other fields
      of mesoscopic biomolecular simulations, are also discussed.

PMID- 12513528
TI  - Adsorption of a random copolymer at a lipid bilayer membrane.
AB  - We examine the conformational properties of a random copolymer, containing a
      disordered hydrophobic/hydrophilic sequence of monomers, in the presence of a
      hydrophobic potential well. The model can be used to understand the structural
      properties of the adsorption of a protein molecule at a lipid-bilayer membrane,
      and the properties of a random copolymer at the surfaces of a microphase
      separated layered polymer structure. Using a trial-potential treatment we
      demonstrate that a mainly hydrophilic chain may localize on the surface of the
      bilayer and that a mainly hydrophobic chain may have two typical conformations:
      localization on the surface or complete adsorption inside the two surfaces.

PMID- 12513529
TI  - Weakly nonlinear analysis of the electrohydrodynamic instability of a charged
      membrane.
AB  - The effect of nonlinear interactions on the linear instability of shape
      fluctuations of a flat charged membrane immersed in a fluid is analyzed using a
      weakly nonlinear stability analysis. There is a linear instability when the
      surface tension reduces below a critical value for a given charge density,
      because a displacement of the membrane surface causes a fluctuation in the
      counterion density at the surface, resulting in an additional Maxwell normal
      stress at the surface which is opposite in direction to the stress caused by
      surface tension. The nonlinear analysis shows that at low surface charge
      densities, the nonlinear interactions saturate the growth of perturbations
      resulting in a new steady state with a fluctuation amplitude determined by the
      balance between the destabilizing electrodynamic force and surface tension. As
      the surface charge density is increased, the nonlinear terms destabilize the
      perturbations, and the bifurcation is subcritical. There is also a significant
      difference in the predictions of the approximate Debye-Huckel and more exact
      Poisson-Boltzmann equations at high charge densities, with the former erroneously
      predicting that the bifurcation is supercritical at all charge densities.

PMID- 12513530
TI  - Unzipping dynamics of long DNAs.
AB  - The two strands of the DNA double helix can be "unzipped" by the application of
      approximately 15 pN force. We analyze the dynamics of unzipping and rezipping for
      the case where the molecule ends are separated and reapproached at constant
      velocity. For unzipping of 50-kilobase DNAs at less than about 1000 bases per
      second, thermal-equilibrium-based theory applies. However, for higher unzipping
      velocities, rotational viscous drag creates a buildup of elastic torque to levels
      above k(B)T in the double-stranded DNA region, causing the unzipping force to be
      well above or well below the equilibrium unzipping force during, respectively,
      unzipping and rezipping, in accord with recent experimental results of Thomen et
      al. [Phys. Rev. Lett. 88, 248102 (2002)]. Our analysis includes the effect of
      sequence on unzipping and rezipping, and the transient delay in buildup of the
      unzipping force due to the approach to the steady state.

PMID- 12513531
TI  - Spatial heterogeneity and the stability of reaction states in autocatalysis.
AB  - The impact of stochasticity and spatial heterogeneity on the quadratic
      autocatalytic system is studied. In a nonspatial setting the reactive state of
      the system is found to be unstable in small volumes where internal fluctuations
      drive the system to the unreactive state. This phenomena is of potential
      importance to the stability of reactions in biological cells. A simple spatial
      model is constructed by linking N nonspatial models via migration of reactants
      controlled by a mixing rate lambda. Simulation of this stochastic process
      demonstrates the importance of such mixing in controlling the impact of internal
      fluctuations on the stability of the autocatalytic reaction. For high mixing rate
      the mean reactant levels in equilibrium correspond to the well-mixed
      deterministic system, although a significant degree of spatial heterogeneity
      remains. For intermediate mixing rates, mean reactant levels vary continuously
      with lambda, where the interaction of internal fluctuations with limited spatial
      mixing modifies the reactive states of the deterministic system. However, there
      is a threshold below which mixing is unable to control internal fluctuations
      which drive the system into the unreactive state. Thus a critical minimum level
      of communication between the cells is required to stabilize the reaction across
      the entire system. Approximate analytic results, obtained using moment-closure
      techniques, support these findings and demonstrate the relationship between the
      spatial stochastic and nonspatial deterministic models.

PMID- 12513532
TI  - Effect of environment partitioning on the survival and coexistence of
      autocatalytic replicators.
AB  - The paradigm of cubic autocatalytic replicators with decay in coupled isothermal
      continuous stirred tank reactors is selected as a model to study complex behavior
      in population dynamics of sexually reproducing species in a heterogenous
      environment. It is shown that, even a setup with single species in two coupled
      environments may have regions in parameter space that result in chaotic behavior,
      hence segregation in the environment causes complexity in the system dynamics.
      Furthermore, partitioning is found to lead to emergence phenomena exemplified by
      steady states not obtainable in the equivalent homogeneous system. These
      phenomena are illustrated through case studies involving single or multiple
      species. Results show that the coupled environments can host species, that would
      not survive should the coupling be removed.

PMID- 12513533
TI  - Population dynamics of interacting spiking neurons.
AB  - A dynamical equation is derived for the spike emission rate nu(t) of a
      homogeneous network of integrate-and-fire (IF) neurons in a mean-field
      theoretical framework, where the activity of the single cell depends both on the
      mean afferent current (the "field") and on its fluctuations. Finite-size effects
      are taken into account, by a stochastic extension of the dynamical equation for
      the nu; their effect on the collective activity is studied in detail. Conditions
      for the local stability of the collective activity are shown to be naturally and
      simply expressed in terms of (the slope of) the single neuron, static, current-to
      rate transfer function. In the framework of the local analysis, we studied the
      spectral properties of the time-dependent collective activity of the finite
      network in an asynchronous state; finite-size fluctuations act as an ongoing self
      stimulation, which probes the spectral structure of the system on a wide
      frequency range. The power spectrum of nu exhibits modes ranging from very high
      frequency (depending on spike transmission delays), which are responsible for
      instability, to oscillations at a few Hz, direct expression of the diffusion
      process describing the population dynamics. The latter "diffusion" slow modes do
      not contribute to the stability conditions. Their characteristic times govern the
      transient response of the network; these reaction times also exhibit a simple
      dependence on the slope of the neuron transfer function. We speculate on the
      possible relevance of our results for the change in the characteristic response
      time of a neural population during the learning process which shapes the synaptic
      couplings, thereby affecting the slope of the transfer function. There is
      remarkable agreement of the theoretical predictions with simulations of a network
      of IF neurons with a constant leakage term for the membrane potential.

PMID- 12513534
TI  - Smectic phases of semiflexible manifolds: constant-pressure ensemble.
AB  - We pursue the constant-pressure ensemble approach to elucidate the statistical
      mechanics of the smectic phases of semiflexible manifolds, such as two
      dimensional smectic phases of long semiflexible polymers and three-dimensional
      lamellar fluid membrane phases. We use this approach to consider in detail
      sterically stabilized phases of semiflexible polymers in two-dimensional (2D)
      smectic systems. For these 2D systems, we obtain the universal constants
      characterizing the entropic repulsion between semiflexible polymers, such as
      those in the osmotic pressure P=alpha(k(B)T)(4/3)/kappa(1/3)(a-a(min))(5/3) with
      alpha found here to be congruent with 0.432 (here, a is the smectic phase period,
      and a(min) and kappa are the polymer cross-sectional diameter and bending
      rigidity constant, respectively). We address, by numerical simulations and
      analytic arguments, finite stacks of N semiflexible manifolds, and discuss in
      detail the practically interesting thermodynamic limit N--> infinity. We show
      that the thermodynamic limit is quickly approached within the constant-pressure
      ensemble: Already from numerical simulations involving just few semiflexible
      polymers under constant isotropic pressure, one can obtain the infinite 2D
      smectic equation of state within a few percent accuracy. We use our results to
      discuss the competition of electrostatic and entropic effects in quasi-2D smectic
      phases of DNA-cationic-lipid complexes. We use our quantitative results to
      discuss in detail the elasticity, topological defects, anomalous elasticity, and
      the effects of externally applied tension in sterically stabilized 2D smectic
      phases of long semiflexible polymers.

PMID- 12513535
TI  - Analysis of microstresses in cement paste by fluorescence piezospectroscopy.
AB  - An experimental method to measure microstresses in cement paste, as a typical
      granular medium, was developed employing a fluorescence microprobe spectroscopy
      method. Stresses were recorded with a Raman spectrometer making use of (Cr3+
      fluorescence lines of) alumina as a piezospectroscopic stress sensor. In a two
      dimensional stress map, fluctuations in the stress distribution led to stress
      chains, indicating the granular character of cement paste. Due to these
      fluctuations, microforces much higher than the macroscopic strength of the
      material existed. The presented technique is proposed as a general tool to
      analyze stresses in cementitious systems. In practice, the method supports the
      development of toughening additives to materials like cement paste.

PMID- 12513536
TI  - Different time regimes of tracer exchange in single-file systems.
AB  - A complete description of the time dependence of tracer exchange in single-file
      systems is given. It is based on the combined application of dynamic Monte Carlo
      simulations and analytical calculations. Depending on the time elapsed, the
      tracer exchange is found to have different time scaling related to transport
      modes of either normal diffusion or single-file diffusion. The mode of single
      file diffusion is reproduced by recent tracer exchange experiments conducted by
      laser-polarized 129Xe NMR spectroscopy.

PMID- 12513537
TI  - Propagation of acoustic waves in nematic elastomers.
AB  - We develop a theory of elastic waves in oriented monodomain nematic elastomers.
      The effect of soft elasticity, combined with the Leslie-Ericksen version of
      dissipation function, results in an unusual dispersion and anomalous anisotropy
      of shear acoustic waves. A characteristic time scale of nematic rotation
      determines the crossover frequency, below which waves of some polarizations have
      a very strong attenuation while others experience no dissipation at all. We study
      the anisotropy of low-frequency Poynting vectors and wave fronts, and discuss a
      "squeeze" effect of energy transfer nonparallel to the wave vector. Based on
      these theoretical results, an application, the acoustic polarizer, is proposed.

PMID- 12513538
TI  - Fluorescence study on the phase transition of hydrogen-bonding gels.
AB  - A technique based on steady-state fluorescence measurements is introduced to
      study the discontinuous volume phase transition of hydrogen-bonding gel. The
      fluorescence light intensity of pyranine (1-Hydroxypyrene-3, 6, 8-trisulfonic
      acid) bonded to the gel by means of methacryl amino-propyl-trimethyl ammonium
      chloride was monitored during the swelling of poly(methacrylic acid-co-dimethyl
      acrylamide) copolymer in water as a function of temperature. A discontinuous
      volume phase transition around 60 degrees C and an additional phase around 30
      degrees C, which may be interpreted as the freely fluctuating phase in a
      collapsed state, were observed when the fluorescence intensity changes.

PMID- 12513539
TI  - Anisotropy of lamellar block copolymer grains.
AB  - The Wulff construction and the theory of Milner and Morse [Phys. Rev. E 54, 3793
      (1996)] were used to calculate the shape of grains formed when a lamellar block
      copolymer phase is formed by a shallow quench into the ordered state. The
      calculations show that the grains are ellipsoids of revolution, with an aspect
      ratio rho=2.37. This value is in reasonable agreement with results of
      transmission electron microscopy and depolarized light scattering experiments,
      which indicate that the average value of rho of grains formed during the early
      stages of the disorder-to-order transition is about 2.0.

PMID- 12513540
TI  - Mechanism for membrane electroporation irreversibility under high-intensity,
      ultrashort electrical pulse conditions.
AB  - An improved electroporation model is used to address membrane irreversibility
      under ultrashort electric pulse conditions. It is shown that membranes can
      survive a strong electric pulse and recover provided the pore distribution has a
      relatively large spread. If, however, the population consists predominantly of
      larger radii pores, then irreversibility can result. Physically, such a
      distribution could arise if pores at adjacent sites coalesce. The requirement of
      close proximity among the pore sites is more easily satisfied in smaller
      organelles than in outer cell membranes. Model predictions are in keeping with
      recent observations of cell damage to intracellular organelles (e.g.,
      mitochondria), without irreversible shock at the outer membranes, by a
      nanosecond, high-intensity electric pulse. This mechanism also explains the
      greater damage from multiple electric shocks.

PMID- 12513541
TI  - Clustering of diffusing organisms.
AB  - Recently, a "Brownian bugs" model has been proposed as a possible explanation for
      the clustering of organisms such as planktons [W.R. Young, A.J. Roberts, and G.
      Stuhne, Nature (London) 412, 328 (2001)]. In this model, diffusing organisms die
      and give birth with equal probabilities and are independent of each other. The
      clustering phenomenon is due to the discreteness of birth and death events and
      cannot be explained in the framework of the continuous model of population
      dynamics. We show by exact calculation that at dimensions smaller than or equal
      to 2, this simple mechanism is enough to provoke aggregations of the organisms.
      At dimensions higher than 2, the clustering phenomenon disappears, but
      reproductive fluctuations can still be large compared to diffusive ones.

PMID- 12513542
TI  - Infinite-order percolation and giant fluctuations in a protein interaction
      network.
AB  - We investigate a model protein interaction network whose links represent
      interactions between individual proteins. This network evolves by the functional
      duplication of proteins, supplemented by random link addition to account for
      mutations. When link addition is dominant, an infinite-order percolation
      transition arises as a function of the addition rate. In the opposite limit of
      high duplication rate, the network exhibits giant structural fluctuations in
      different realizations. For biologically relevant growth rates, the node degree
      distribution has an algebraic tail with a peculiar rate dependence for the
      associated exponent.

PMID- 12513543
TI  - Monochromatic path crossing exponents and graph connectivity in two-dimensional
      percolation.
AB  - We consider the fractal dimensions d(k) of the k-connected part of percolation
      clusters in two dimensions, generalizing the cluster (k=1) and backbone (k=2)
      dimensions. The codimensions x(k)=2-d(k) describe the asymptotic decay of the
      probabilities P(r,R) approximately (r/R)(x(k)) that an annulus of radii r<<1 and
      R>>1 is traversed by k disjoint paths, all living on the percolation clusters.
      Using a transfer matrix approach, we obtain numerical results for x(k), k<or=6.
      They are well fitted by the ansatz x(k)=1 / 12k(2)+1 / 48k+(1-k)C, with
      C=0.0181+/-0.0006.

PMID- 12513544
TI  - Dominance of Milnor attractors in globally coupled dynamical systems with more
      than 7+/-2 degrees of freedom.
AB  - The prevalence of Milnor attractors has recently been reported in a class of high
      dimensional dynamical systems. We study how this prevalence depends on the number
      of degrees of freedom by using a globally coupled map and show that the basin
      fraction of Milnor attractors increases drastically around 5-10 degrees of
      freedom, saturating for higher numbers of degrees of freedom. It is argued that
      this dominance of Milnor attractors in the basin arises from a combinatorial
      explosion of the basin boundaries. In addition, the dominance is also found in a
      system without permutation symmetry, i.e., a coupled dynamical system of
      nonidentical elements. Possible relevance to the magic number 7+/-2 in psychology
      is briefly discussed.

PMID- 12513545
TI  - Phase synchronization and topological defects in inhomogeneous media.
AB  - The influence of topological defects on phase synchronization and phase coherence
      in two-dimensional arrays of locally coupled, nonidentical, chaotic oscillators
      is investigated. The motion of topological defects leads to a breakdown of phase
      synchronization in the vicinities of the defects; however, the system is much
      more phase coherent as long as the coupling between the oscillators is strong
      enough to prohibit the continuous dynamical creation and annihilation of defects.
      The generic occurrence of topological defects in two and higher dimensions
      implies that the concept of phase synchronization has to be modified for these
      systems.

PMID- 12513546
TI  - Patterns in spherical Rayleigh-Benard convection: a giant spiral roll and its
      dislocations.
AB  - Thermal convection in a moderately thin spherical fluid layer in the presence of
      spherically symmetric gravity, spherical Rayleigh-Benard convection, is
      investigated through fully three-dimensional numerical simulations. A steady
      spherical pattern in the form of a single giant spiral roll covering the whole
      spherical surface without defects is discovered near the onset of convection.
      Successive dislocations of the giant spiral roll are also found at larger
      Rayleigh numbers.

PMID- 12513547
TI  - Soret driven convection in a colloidal solution heated from above at very large
      solutal Rayleigh number.
AB  - Convection in a colloidal suspension with a large negative separation ratio psi
      is studied experimentally by heating from above. Shadowgraph observations at very
      large solutal Rayleigh numbers Rtilde; are reported as a function of time. Fast
      relaxation oscillations are reported for the root mean square value of the
      shadowgraph intensity. While pure fluids exhibit a transition to turbulent
      convection for Rayleigh number R approximately 10(6), stable spoke-pattern
      planform with up and down columnar flows are observed up to Rtilde; approximately
      1.9 x 10(9). It is suggested that the surprising stability of the planform
      against turbulence is due to nonlinear focusing arising from the concentration
      dependence of the diffusion coefficient.

PMID- 12513548
TI  - Optimal bistable switching in nonlinear photonic crystals.
AB  - We present an analytical model and numerical experiments to describe optimal
      bistable switching in a nonlinear photonic crystal system. It is proved that only
      three parameters are needed to characterize a bistable switch: the resonant
      frequency omega(res), the quality factor Q, and parameter kappa that measures
      nonlinear "feedback strength." A photonic crystal enables the device to operate
      in single-mode fashion, as if it were effectively one dimensional. This provides
      optimal control over the input and output and facilitates further large-scale
      optical integration.

PMID- 12513549
TI  - Stability of spiralling solitary waves in Hamiltonian systems.
AB  - We present a rigorous criterion for stability of spiralling solitary structures
      in Hamiltonian systems incorporating the angular momentum integral and
      demonstrate its applicability to the spiralling of two mutually incoherent
      optical beams propagating in a photorefractive material.

PMID- 12513550
TI  - Scaling analysis of a divergent prefactor in the metastable lifetime of a square
      lattice Ising ferromagnet at low temperatures.
AB  - We examine a square-lattice nearest-neighbor Ising quantum ferromagnet coupled to
      d-dimensional phonon baths. Using the density-matrix equation, we calculate the
      transition rates between configurations, which determines the specific dynamic.
      Applying the calculated stochastic dynamic in Monte Carlo simulations, we measure
      the lifetimes of the metastable state. As the magnetic field approaches [H]/J=2
      at low temperatures, the lifetime prefactor diverges because the transition rates
      between certain configurations approach zero under these conditions. Near [H]/J=2
      and zero temperature, the divergent prefactor shows scaling behavior as a
      function of the field, temperature, and the dimension of the phonon baths. With
      proper scaling, the simulation data at different temperatures and for different
      dimensions of the baths collapse well onto two master curves, one for [H]/J>2 and
      one for [H]/J<2.

PMID- 12513551
TI  - Singularities of the canonical partition functions of fluid systems with
      continuous interaction potentials.
AB  - We observe that for finite N and V, the canonical partition function Q(N) of a
      fluid system of N particles is a polynomial of degree N in variable V/Nlambda(3),
      which has N zeros that depend only on the cluster integrals b(2)(V,T), em
      leader,b(N)(V,T). In the thermodynamic limit, if the zero distribution approaches
      the positive real axis, a phase transition arises. The behavior of phase
      transition is determined solely by the zero distribution near the positive real
      axis. Below the critical temperature, the Maxwell's equal-area rule must be used
      to obtain the gas-liquid coexistence regime. Several examples are given.

PMID- 12513552
TI  - Exact results for hydrogen recombination on dust grain surfaces.
AB  - The recombination of hydrogen in the interstellar medium, taking place on
      surfaces of microscopic dust grains, is an essential process in the evolution of
      chemical complexity in interstellar clouds. Molecular hydrogen plays an important
      role in absorbing the heat that emerges during gravitational collapse, thus
      enabling the formation of structure in the universe. The H2 formation process has
      been studied theoretically, and in recent years also by laboratory experiments.
      The experimental results were analyzed using a rate equation model. The
      parameters of the surface that are relevant to H2 formation were obtained and
      used in order to calculate the recombination rate under interstellar conditions.
      However, it turned out that, due to the microscopic size of the dust grains and
      the low density of H atoms, the rate equations may not always apply. A master
      equation approach that provides a good description of the H2 formation process
      was proposed. It takes into account both the discrete nature of the H atoms and
      the fluctuations in the number of atoms on a grain. In this paper we present a
      comprehensive analysis of the H2 formation process, under steady state
      conditions, using an exact solution of the master equation. This solution
      provides an exact result for the hydrogen recombination rate and its dependence
      on the flux, the surface temperature, and the grain size. The results are
      compared with those obtained from the rate equations. The relevant length scales
      in the problem are identified and the parameter space is divided into two
      domains. One domain, characterized by first order kinetics, exhibits high
      efficiency of H2 formation. In the other domain, characterized by second order
      kinetics, the efficiency of H2 formation is low. In each of these domains we
      identify the range of parameters in which, due to the small size of the grains,
      the rate equations do not account correctly for the recombination rate and the
      master equation is needed.

PMID- 12513553
TI  - Aggregate formation in a system of coagulating and fragmenting particles with
      mass-dependent diffusion rates.
AB  - The effect of introducing a mass-dependent diffusion rate approximately m(-alpha)
      in a model of coagulation with single-particle breakup is studied both
      analytically and numerically. The model with alpha=0 is known to undergo a
      nonequilibrium phase transition as the mass density in the system is varied from
      a phase with an exponential distribution of mass to a phase with a power-law
      distribution of masses in addition to a single infinite aggregate. This
      transition is shown to be curbed, at finite densities, for all alpha>0 in any
      dimension. However, a signature of this transition is seen in finite systems in
      the form of a large aggregate and the finite-size scaling implications of this
      are characterized. The exponents characterizing the steady-state probability that
      a randomly chosen site has mass m are calculated using scaling arguments. The
      full probability distribution is obtained within a mean-field approximation and
      found to compare well with the results from numerical simulations in one
      dimension.

PMID- 12513554
TI  - Geography in a scale-free network model.
AB  - We offer an example of a network model with a power-law degree distribution, P(k)
      approximately k(-alpha), for nodes, but which nevertheless has a well-defined
      geography and a nonzero threshold percolation probability for alpha>2, the range
      of real-world contact networks. This is different from p(c)=0 for alpha<3 results
      for the original well-mixed scale-free networks. In our lattice-based scale-free
      network, individuals link to nearby neighbors on a lattice. Even considerable
      additional small-world links do not change our conclusion of nonzero thresholds.
      When applied to disease propagation, these results suggest that random
      immunization may be more successful in controlling human epidemics than
      previously suggested if there is geographical clustering.

PMID- 12513555
TI  - Importance of multispin couplings in renormalized Hamiltonians.
AB  - We introduce a Monte Carlo approach to the calculation of more distant
      renormalized interactions with higher accuracy than is possible with previous
      methods. We have applied our method to study the effects of multispin
      interactions, which turn out to be far more important than commonly assumed. Even
      though the individual multispin interactions usually have smaller coupling
      constants than two-spin interactions, they can dominate the effects of two-spin
      interactions because they are so numerous.

PMID- 12513556
TI  - Largest and second largest cluster statistics at the percolation threshold of
      hypercubic lattices.
AB  - We investigate the scale invariance of the average ratio between the masses of
      the largest and second largest clusters at percolation. We employ a finite size
      scaling method to estimate percolation thresholds based on the simulations of
      relatively small lattices, and report on estimates for p(c) in hypercubic
      lattices with d=2-7, in full agreement with the best literature estimates. Also,
      we find the critical mass ratio to be strongly dependent on the boundary
      conditions, decreasing with the lattice dimension. Further, we compute several
      relevant mass distribution functions associated with the two largest clusters,
      which approach to limiting distributions for d>6. Finally, we discuss the main
      relevant features of the mass distributions in light of the relative role played
      by the spanning and nonspanning clusters.

PMID- 12513557
TI  - Fractional Schrodinger equation.
AB  - Some properties of the fractional Schrodinger equation are studied. We prove the
      Hermiticity of the fractional Hamilton operator and establish the parity
      conservation law for fractional quantum mechanics. As physical applications of
      the fractional Schrodinger equation we find the energy spectra of a hydrogenlike
      atom (fractional "Bohr atom") and of a fractional oscillator in the semiclassical
      approximation. An equation for the fractional probability current density is
      developed and discussed. We also discuss the relationships between the fractional
      and standard Schrodinger equations.

PMID- 12513558
TI  - Phase transitions of soft disks in external periodic potentials: a Monte Carlo
      study.
AB  - The nature of freezing and melting transitions for a system of model colloids
      interacting via the Derjaguin, Landau, Verwey, and Overbeek potential in a
      spatially periodic external potential is studied using extensive Monte Carlo
      simulations. Detailed finite size scaling analyses of various thermodynamic
      quantities, such as the order parameter, its cumulants, etc., are used to map the
      phase diagram of the system for various values of the reduced screening length
      kappaa(s) and the amplitude of the external potential. We find clear indication
      of a reentrant liquid phase over a significant region of the parameter space. Our
      simulations therefore show that the system of soft disks behaves in a fashion
      similar to charge stabilized colloids, which are known to undergo an initial
      freezing, followed by a remelting transition as the amplitude of the imposed,
      modulating field produced by crossed laser beams is steadily increased. The
      detailed analysis of our data shows several features consistent with a recent
      dislocation unbinding theory of laser induced melting.

PMID- 12513559
TI  - Large scale cross-correlations in Internet traffic.
AB  - The Internet is a complex network of interconnected routers, and the existence of
      a collective behavior such as congestion suggests that the correlations between
      the different connections play a crucial role. It is thus critical to measure and
      quantify these correlations. We use methods of random matrix theory (RMT) to
      analyze the cross-correlation matrix C of information flow changes of 650
      connections between 26 routers of the French scientific network "Renater." We
      find that C has the universal properties of the Gaussian orthogonal ensemble of
      random matrices: The distribution of eigenvalues-up to a rescaling that exhibits
      a typical correlation time of the order of 10 min-and the spacing distribution
      follow the predictions of RMT. There are some deviations for large eigenvalues
      which contain network-specific information and which identify genuine
      correlations between the connections. The study of the most correlated
      connections reveals the existence of "active centers" that are exchanging
      information with a large number of routers thereby inducing correlations between
      the corresponding connections. These strong correlations could be a reason for
      the observed self-similarity in the world-wide web traffic.

PMID- 12513560
TI  - Continuum analysis of an avalanche model for solar flares.
AB  - We investigate the continuum limit of a class of self-organized critical lattice
      models for solar flares. Such models differ from the classical numerical sandpile
      model in their formulation of stability criteria in terms of the curvature of the
      nodal field, and are known to belong to a different universality class. A fourth
      order nonlinear hyperdiffusion equation is reverse engineered from the discrete
      model's redistribution rule. A dynamical renormalization-group analysis of the
      equation yields scaling exponents that compare favorably with those measured in
      the discrete lattice model within the relevant spectral range dictated by the
      sizes of the domain and the lattice grid. We argue that the fourth-order
      nonlinear diffusion equation that models the behavior of the discrete model in
      the continuum limit is, in fact, compatible with magnetohydrodynamics (MHD) of
      the flaring phenomenon in the regime of strong magnetic field and the effective
      magnetic diffusivity characteristic of strong MHD turbulence.

PMID- 12513561
TI  - Slow dynamics in the three-dimensional gonihedric model.
AB  - We study dynamical aspects of three-dimensional gonihedric spins by using Monte
      Carlo methods. These models have a purely geometrical motivation, deriving from
      string and random surface theory. Here, however, we shall analyze this family of
      models just from a statistical point of view. In particular, we shall be
      concerned with their ability to exhibit remarkably slow dynamics and seemingly
      glassy behavior below a certain temperature T(g), without the need of introducing
      disorder of any kind. We consider first a Hamiltonian that takes into account
      only a four-spin term (kappa=0), where a first-order phase transition is well
      established. By studying the relaxation properties at low temperatures, we
      confirm that the model exhibits two distinct regimes. For T(g)<T<T(c), with long
      lived metastability and a supercooled phase, the approach to equilibrium is well
      described by a stretched exponential. For T<T(g), the dynamics appears to be
      logarithmic. We provide an accurate determination of T(g). We also determine the
      evolution of particularly long lived configurations. Next, we consider the case
      kappa=1, where the plaquette term is absent and the gonihedric action consists in
      a ferromagnetic Ising with fine-tuned next-to-nearest neighbor interactions. This
      model exhibits a second order phase transition. The consideration of the
      relaxation time for configurations in the cold phase reveals the presence of slow
      dynamics and glassy behavior for any T<T(c). Type-II aging features are exhibited
      by this model.

PMID- 12513562
TI  - Percolation in a random environment.
AB  - We consider bond percolation on the square lattice with perfectly correlated
      random probabilities. According to scaling considerations, mapping to a random
      walk problem and the results of Monte Carlo simulations the critical behavior of
      the system with varying degree of disorder is governed by new, random fixed
      points with anisotropic scaling properties. For weaker disorder both the
      magnetization and the anisotropy exponents are nonuniversal, whereas for strong
      enough disorder the system scales into an infinite randomness fixed point in
      which the critical exponents are exactly known.

PMID- 12513563
TI  - Slow relaxation in a constrained Ising spin chain: toy model for granular
      compaction.
AB  - We present detailed analytical studies on the zero-temperature coarsening
      dynamics in an Ising spin chain in the presence of a dynamically induced field
      that favors locally the "-" phase compared to the "+" phase. We show that the
      presence of such a local kinetic bias drives the system into a late time state
      with average magnetization m equal to -1. However the magnetization relaxes into
      this final value extremely slowly in an inverse logarithmic fashion. We further
      map this spin model exactly onto a simple lattice model of granular compaction
      that includes the minimal microscopic moves needed for compaction. This toy model
      then predicts analytically an inverse logarithmic law for the growth of density
      of granular particles, as seen in recent experiments and thereby provides a
      mechanism for the inverse logarithmic relaxation. Our analysis utilizes an
      independent interval approximation for the particle and the hole clusters and is
      argued to be exact at late times (supported also by numerical simulations).

PMID- 12513564
TI  - Contact tracing and epidemics control in social networks.
AB  - A generalization of the standard susceptible-infectious-removed stochastic model
      for epidemics in sparse random networks is introduced which incorporates contact
      tracing in addition to random screening. We propose a deterministic mean-field
      description that yields quantitative agreement with stochastic simulations on
      random graphs. Both the stochastic simulations and the mean-field equations show
      secondary epidemics if the contact tracing is not performed with sufficient
      strength. We also analyze the role of contact tracing in epidemics control in
      small-world networks and show that its effectiveness grows as the rewiring
      probability is reduced.

PMID- 12513565
TI  - Pure stationary states of open quantum systems.
AB  - Using Liouville space and superoperator formalism we consider pure stationary
      states of open and dissipative quantum systems. We discuss stationary states of
      open quantum systems, which coincide with stationary states of closed quantum
      systems. Open quantum systems with pure stationary states of linear oscillator
      are suggested. We consider stationary states for the Lindblad equation. We
      discuss bifurcations of pure stationary states for open quantum systems which are
      quantum analogs of classical dynamical bifurcations.

PMID- 12513566
TI  - Edge wetting of an Ising three-dimensional system.
AB  - The effect of edge on wetting and layering transitions of a three-dimensional
      spin-1/2 Ising model is investigated, in the presence of longitudinal and surface
      magnetic fields, using mean field theory and Monte Carlo simulations. For T=0,
      the ground state phase diagram shows that there exist only three allowed
      transitions, namely, surface and bulk transition, surface transition, and bulk
      transition. However, there exist a surface intralayering temperature T(s)(L),
      above which the surface and the intralayering surface transitions occur. While
      the bulk layering and intralayering transitions appear above another finite
      temperature T(b)(L)(>or=T(s)(L)). These surface and bulk intralayering
      transitions are not seen in the perfect surfaces case. Numerical values of
      T(s)(L) and T(b)(L), computed by Monte Carlo method are found to be smaller than
      those obtained using mean field theory. However, the results predicted by the two
      methods become similar, and are exactly those given by the ground state phase
      diagram, for very low temperatures. On the other hand, the behavior of the local
      magnetizations as a function of the external magnetic field, shows that the
      transitions are of the first order type. T(s)(L) and T(b)(L) decrease when
      increasing the system size and/or the surface magnetic field. In particular,
      T(b)(L) reaches the wetting temperature T(w) for sufficiently large system sizes.

PMID- 12513567
TI  - Coevolutionary games on networks.
AB  - We study agents on a network playing an iterated Prisoner's dilemma against their
      neighbors. The resulting spatially extended coevolutionary game exhibits
      stationary states which are Nash equilibria. After perturbation of these
      equilibria, avalanches of mutations reestablish a stationary state. Scale-free
      avalanche distributions are observed that are in accordance with calculations
      from the Nash equilibria and a confined branching process. The transition from
      subcritical to critical avalanche dynamics can be traced to a change in the
      degeneracy of the cooperative macrostate and is observed for many variants of
      this game.

PMID- 12513568
TI  - Information geometry of the ising model on planar random graphs.
AB  - It has been suggested that an information geometric view of statistical mechanics
      in which a metric is introduced onto the space of parameters provides an
      interesting alternative characterization of the phase structure, particularly in
      the case where there are two such parameters, such as the Ising model with
      inverse temperature beta and external field h. In various two-parameter
      calculable models, the scalar curvature R of the information metric has been
      found to diverge at the phase transition point beta(c) and a plausible scaling
      relation postulated: R approximately |beta-beta(c)|(alpha-2). For spin models the
      necessity of calculating in nonzero field has limited analytic consideration to
      one-dimensional, mean-field and Bethe lattice Ising models. In this paper we use
      the solution in field of the Ising model on an ensemble of planar random graphs
      (where alpha=-1, beta=1/2, gamma=2) to evaluate the scaling behavior of the
      scalar curvature, and find R approximately |beta-beta(c)|(-2). The apparent
      discrepancy is traced back to the effect of a negative alpha.

PMID- 12513569
TI  - Random graph coloring: statistical physics approach.
AB  - The problem of vertex coloring in random graphs is studied using methods of
      statistical physics and probability. Our analytical results are compared to those
      obtained by exact enumeration and Monte Carlo simulations. We critically discuss
      the merits and shortcomings of the various methods, and interpret the results
      obtained. We present an exact analytical expression for the two-coloring problem
      as well as general replica symmetric approximated solutions for the
      thermodynamics of the graph coloring problem with p colors and K-body edges.

PMID- 12513570
TI  - Multifractal stationary random measures and multifractal random walks with log
      infinitely divisible scaling laws.
AB  - We define a large class of continuous time multifractal random measures and
      processes with arbitrary log infinitely divisible exact or asymptotic scaling
      law. These processes generalize within a unified framework both the recently
      defined log-normal multifractal random walk [J.F. Muzy, J. Delour, and E. Bacry,
      Eur. J. Phys. B 17, 537 (2000), E. Bacry, J. Delour, and J.F. Muzy, Phys. Rev. E
      64, 026103 (2001)] and the log-Poisson "product of cylindrical pulses" [J. Barral
      and B.B. Mandelbrot, Cowles Foundation Discussion Paper No. 1287, 2001
      (unpublished)]. Our construction is based on some "continuous stochastic
      multiplication" [as introduced in F. Schmitt and D. Marsan, Eur. J. Phys. B. 20,
      3 (2001)] from coarse to fine scales that can be seen as a continuous
      interpolation of discrete multiplicative cascades. We prove the stochastic
      convergence of the defined processes and study their main statistical properties.
      The question of genericity (universality) of limit multifractal processes is
      addressed within this new framework. We finally provide a method for numerical
      simulations and discuss some specific examples.

PMID- 12513571
TI  - Trapping thresholds in invasion percolation.
AB  - We give numerical estimates for the site percolation trapping thresholds for
      invasion percolation on various three dimensional lattices. We find that in most
      cases the thresholds for invasion and ordinary percolation coincide. However, for
      coordination numbers less than five the thresholds diverge. Since most rock
      networks exhibit coordination numbers less than five the rules for simulating
      residual saturation in porous rocks must be chosen carefully.

PMID- 12513572
TI  - Quantum statistics in complex networks.
AB  - In this work we discuss the symmetric construction of bosonic and fermionic
      networks and we present a case of a network showing a mixed quantum statistics.
      This model takes into account the different nature of nodes, described by a
      random parameter that we call energy, and includes rewiring of the links. The
      system described by the mixed statistics is an inhomogeneous system formed by two
      class of nodes. In fact there is a threshold energy epsilon(s) such that nodes
      with lower energy (epsilon<epsilon(s)) increase their connectivity, while nodes
      with higher energy (epsilon>epsilon(s)) decrease their connectivity in time.

PMID- 12513573
TI  - Effects of pore walls and randomness on phase transitions in porous media.
AB  - We study spin models within the mean field approximation to elucidate the
      topology of the phase diagrams of systems modeling the liquid-vapor transition
      and the separation of 3He-4He mixtures in periodic porous media. These topologies
      are found to be identical to those of the corresponding random field and random
      anisotropy spin systems with a bimodal distribution of the randomness. Our
      results suggest that the presence of walls (periodic or otherwise) are a key
      factor determining the nature of the phase diagram in porous media.

PMID- 12513574
TI  - Statistical mechanics in the context of special relativity.
AB  - In Ref. [Physica A 296, 405 (2001)], starting from the one parameter deformation
      of the exponential function exp(kappa)(x)=(sqrt[1+kappa(2)x(2)]+kappax)(1/kappa),
      a statistical mechanics has been constructed which reduces to the ordinary
      Boltzmann-Gibbs statistical mechanics as the deformation parameter kappa
      approaches to zero. The distribution f=exp(kappa)(-beta E+betamu) obtained within
      this statistical mechanics shows a power law tail and depends on the nonspecified
      parameter beta, containing all the information about the temperature of the
      system. On the other hand, the entropic form S(kappa)= integral d(3)p(c(kappa)
      f(1+kappa)+c(-kappa) f(1-kappa)), which after maximization produces the
      distribution f and reduces to the standard Boltzmann-Shannon entropy S0 as kappa-
      >0, contains the coefficient c(kappa) whose expression involves, beside the
      Boltzmann constant, another nonspecified parameter alpha. In the present effort
      we show that S(kappa) is the unique existing entropy obtained by a continuous
      deformation of S0 and preserving unaltered its fundamental properties of
      concavity, additivity, and extensivity. These properties of S(kappa) permit to
      determine unequivocally the values of the above mentioned parameters beta and
      alpha. Subsequently, we explain the origin of the deformation mechanism
      introduced by kappa and show that this deformation emerges naturally within the
      Einstein special relativity. Furthermore, we extend the theory in order to treat
      statistical systems in a time dependent and relativistic context. Then, we show
      that it is possible to determine in a self consistent scheme within the special
      relativity the values of the free parameter kappa which results to depend on the
      light speed c and reduces to zero as c--> infinity recovering in this way the
      ordinary statistical mechanics and thermodynamics. The statistical mechanics here
      presented, does not contain free parameters, preserves unaltered the mathematical
      and epistemological structure of the ordinary statistical mechanics and is
      suitable to describe a very large class of experimentally observed phenomena in
      low and high energy physics and in natural, economic, and social sciences.
      Finally, in order to test the correctness and predictability of the theory, as
      working example we consider the cosmic rays spectrum, which spans 13 decades in
      energy and 33 decades in flux, finding a high quality agreement between our
      predictions and observed data.

PMID- 12513575
TI  - Random K-satisfiability problem: from an analytic solution to an efficient
      algorithm.
AB  - We study the problem of satisfiability of randomly chosen clauses, each with K
      Boolean variables. Using the cavity method at zero temperature, we find the phase
      diagram for the K=3 case. We show the existence of an intermediate phase in the
      satisfiable region, where the proliferation of metastable states is at the origin
      of the slowdown of search algorithms. The fundamental order parameter introduced
      in the cavity method, which consists of surveys of local magnetic fields in the
      various possible states of the system, can be computed for one given sample.
      These surveys can be used to invent new types of algorithms for solving hard
      combinatorial optimizations problems. One such algorithm is shown here for the
      K=3 satisfiability problem, with very good performances.

PMID- 12513576
TI  - Absence of first-order transition and tricritical point in the dynamic phase
      diagram of a spatially extended bistable system in an oscillating field.
AB  - It has been well established that spatially extended, bistable systems that are
      driven by an oscillating field exhibit a nonequilibrium dynamic phase transition
      (DPT). The DPT occurs when the field frequency is of the order of the inverse of
      an intrinsic lifetime associated with the transitions between the two stable
      states in a static field of the same magnitude as the amplitude of the
      oscillating field. The DPT is continuous and belongs to the same universality
      class as the equilibrium phase transition of the Ising model in zero field [G.
      Korniss et al., Phys. Rev. E 63, 016120 (2001); H. Fujisaka et al., Phys. Rev. E
      63, 036109 (2001)]. However, it has previously been claimed that the DPT becomes
      discontinuous at temperatures below a tricritical point [M. Acharyya, Phys. Rev.
      E 59, 218 (1999)]. This claim was based on observations in dynamic Monte Carlo
      simulations of a multipeaked probability density for the dynamic order parameter
      and negative values of the fourth-order cumulant ratio. Both phenomena can be
      characteristic of discontinuous phase transitions. Here we use classical
      nucleation theory for the decay of metastable phases, together with data from
      large-scale dynamic Monte Carlo simulations of a two-dimensional kinetic Ising
      ferromagnet, to show that these observations in this case are merely finite-size
      effects. For sufficiently small systems and low temperatures, the continuous DPT
      is replaced, not by a discontinuous phase transition, but by a crossover to
      stochastic resonance. In the infinite-system limit, the stochastic-resonance
      regime vanishes, and the continuous DPT should persist for all nonzero
      temperatures.

PMID- 12513577
TI  - Ramanujan sums for signal processing of low-frequency noise.
AB  - An aperiodic (low-frequency) spectrum may originate from the error term in the
      mean value of an arithmetical function such as Mobius function or Mangoldt
      function, which are coding sequences for prime numbers. In the discrete Fourier
      transform the analyzing wave is periodic and not well suited to represent the low
      frequency regime. In place we introduce a different signal processing tool based
      on the Ramanujan sums c(q)(n), well adapted to the analysis of arithmetical
      sequences with many resonances p/q. The sums are quasiperiodic versus the time n
      and aperiodic versus the order q of the resonance. Different results arise from
      the use of this Ramanujan-Fourier transform in the context of arithmetical and
      experimental signals.

PMID- 12513578
TI  - Stochastic synchronization in globally coupled phase oscillators.
AB  - Cooperative effects of periodic force and noise in globally coupled systems are
      studied using a nonlinear diffusion equation for the number density. The
      amplitude of the order parameter oscillation is enhanced in an intermediate range
      of noise strength for a globally coupled bistable system, and the order parameter
      oscillation is entrained to the external periodic force in an intermediate range
      of noise strength. These enhancement phenomena of the response of the order
      parameter in the deterministic equations are interpreted as stochastic resonance
      and stochastic synchronization in globally coupled systems.

PMID- 12513579
TI  - Defect-induced perturbations of atomic monolayers on solid surfaces.
AB  - We study long-range morphological changes in atomic monolayers on solid
      substrates induced by different types of defects; e.g., by monoatomic steps in
      the surface, or by the tip of an atomic force microscope (AFM), placed at some
      distance above the substrate. Representing the monolayer in terms of a suitably
      extended Frenkel-Kontorova-type model, we calculate the defect-induced density
      profiles for several possible geometries. In case of an AFM tip, we also
      determine the extra force exerted on the tip due to the tip-induced
      dehomogenization of the monolayer.

PMID- 12513580
TI  - Entropy and bifurcations in a chaotic laser.
AB  - We compute bounds on the topological entropy associated with a chaotic attractor
      of a semiconductor laser with optical injection. We consider the Poincare return
      map to a fixed plane, and are able to compute the stable and unstable manifolds
      of periodic points globally, even though it is impossible to find a plane on
      which the Poincare map is globally smoothly defined. In this way, we obtain the
      information that forms the input of the entropy calculations, and characterize
      the boundary crisis in which the chaotic attractor is destroyed. This boundary
      crisis involves a periodic point with negative eigenvalues, and the entropy
      associated with the chaotic attractor persists in a chaotic saddle after the
      bifurcation.

PMID- 12513581
TI  - Quantization conditions in Bogomolny's transfer operator method.
AB  - Bogomolny's transfer operator method plays a significant role in the study of
      quantum chaos, along with other well known methods like Gutzwiller's trace
      formula and the dynamical zeta function, which generalize the Einstein-Brillouin
      Keller quantization rule from integrable systems to chaotic systems. According to
      the theory, the Fredholm determinant of the transfer operator, defined on a
      Poincare section of a classical physical system, provides a quantization
      condition to the energy spectrum of the corresponding quantum system. This study
      presents two factorization formulas, which relate different quantization
      conditions defined on different classical trajectory segments. These explicit
      relations answer the question of why all these classical quantization conditions
      determine exactly the same energy spectrum of the corresponding quantum systems.
      As an example, these formulas are illustrated in the equilateral triangular
      billiard.

PMID- 12513582
TI  - Phase synchronization in coupled chaotic oscillators with time delay.
AB  - The phase synchronization (PS) of two Rossler oscillators with time-delayed
      signal coupling is studied. We find that time delay can always lead to PS even
      when the delay is very long. Moreover, with the increase of time delay, the
      coupling strength at the transition to PS undergoes a nearly periodic wave
      distribution. At some fixed time-delayed signal coupling, a PS region is followed
      by a non-PS region when the coupling strength increases. However, an increase of
      the coupling leads to the PS state again. This phenomenon occurs in systems with
      a relatively large PS transition point.

PMID- 12513583
TI  - Bubble and spherical air shell formation dynamics.
AB  - We studied the formation dynamics of air bubbles emitted from a nozzle submerged
      in aqueous glycerol solutions of different viscosities. We describe the evolution
      of the bubbling regimes by using the air flow rate as a control parameter and the
      time between successive bubbles as a dynamical variable. Some results concerning
      bubbling coalescence were emulated with a combination of simple maps. We also
      observed the formation of air shells surrounding liquid drops inside the liquid,
      known as antibubbles. The antibubbling conditions were related to an intermittent
      regime.

PMID- 12513584
TI  - Dynamical effects induced by long range activation in a nonequilibrium reaction
      diffusion system.
AB  - We show both experimentally and numerically that the time scales separation
      introduced by long range activation can induce oscillations and excitability in
      nonequilibrium reaction-diffusion systems that would otherwise only exhibit
      bistability. Namely, we show that in the chlorite-tetrathionate reaction, where
      the autocatalytic species H+ diffuses faster than the substrates, the spatial
      bistability domain in the nonequilibrium phase diagram is extended with
      oscillatory and excitability domains. A simple model and a more realistic model
      qualitatively account for the observed dynamical behavior. The latter model
      provides quantitative agreement with the experiments.

PMID- 12513585
TI  - Dynamical fidelity of a solid-state quantum computation.
AB  - In this paper we analyze the dynamics in a spin model of quantum computer. Main
      attention is paid to the dynamical fidelity (associated with dynamical errors) of
      an algorithm that allows to create an entangled state for remote qubits. We show
      that in the regime of selective resonant excitations of qubits there is no danger
      of quantum chaos. Moreover, in this regime a modified perturbation theory gives
      an adequate description of the dynamics of the system. Our approach allows us to
      explicitly describe all peculiarities of the evolution of the system under time
      dependent pulses corresponding to a quantum protocol. Specifically, we analyze,
      both analytically and numerically, how the fidelity decreases in dependence on
      the model parameters.

PMID- 12513586
TI  - Quantum chaos in optical systems: the annular billiard.
AB  - We study the dielectric annular billiard as a quantum chaotic model of a micro
      optical resonator. It differs from conventional billiards with hard-wall boundary
      conditions in that it is partially open and composed of two dielectric media with
      different refractive indices. The interplay of reflection and transmission at the
      different interfaces gives rise to rich dynamics of classical light rays and to a
      variety of wave phenomena. We study the ray propagation in terms of Poincare
      surfaces of section and complement it with full numerical solutions of the
      corresponding wave equations. We introduce and develop an S-matrix approach to
      open optical cavities which proves very suitable for the identification of
      resonances of intermediate width that will be most important in future
      applications like optical communication devices. We show that the Husimi
      representation is a useful tool in characterizing resonances and establish the
      ray-wave correspondence in real and phase space. While the simple ray picture
      provides a good qualitative description of certain system classes, only the wave
      description reveals the quantitative details.

PMID- 12513587
TI  - Crossover of quantum Loschmidt echo from golden-rule decay to perturbation
      independent decay.
AB  - We study the crossover of the quantum Loschmidt echo (or fidelity) from the
      golden-rule regime to the perturbation-independent exponential decay regime by
      using the kicked top model. It is shown that the deviation of the perturbation
      independent decay of the averaged fidelity from the Lyapunov decay results from
      quantum fluctuations in individual fidelity, which are caused by the coherence in
      the initial coherent states. With an averaging procedure suppressing the quantum
      fluctuations effectively, the perturbation-independent decay is found to be close
      to the Lyapunov decay. We also show that the Fourier transform of the fidelity is
      determined directly by the initial state and the eigenstates of the Floquet
      operators of the two classically chaotic systems concerned. The absolute value
      part and the phase part of the Fourier transform of the fidelity are found to be
      divided into several correlated parts, which is a manifestation of the coherence
      of the initial coherent state. In the whole crossover region, some important
      properties of the fidelity, such as the exponent of its exponential decay and the
      short initial time within which the fidelity almost does not change, are found to
      be closely related to the properties of the central part of its Fourier
      transform.

PMID- 12513588
TI  - Context-tree modeling of observed symbolic dynamics.
AB  - Modern techniques invented for data compression provide efficient automated
      algorithms for the modeling of the observed symbolic dynamics. We demonstrate the
      relationship between coding and modeling, motivating the well-known minimum
      description length (MDL) principle, and give concrete demonstrations of the
      "context-tree weighting" and "context-tree maximizing" algorithms. The predictive
      modeling technique obviates many of the technical difficulties traditionally
      associated with the correct MDL analyses. These symbolic models, representing the
      symbol generating process as a finite-state automaton with probabilistic emission
      probabilities, provide excellent and reliable entropy estimations. The
      resimulations of estimated tree models satisfying the MDL model-selection
      criterion are faithful to the original in a number of measures. The modeling
      suggests that the automated context-tree model construction could replace fixed
      order word lengths in many traditional forms of empirical symbolic analysis of
      the data. We provide an explicit pseudocode for implementation of the context
      tree weighting and maximizing algorithms, as well as for the conversion to an
      equivalent Markov chain.

PMID- 12513589
TI  - Early time diffusion for the quantum kicked rotor with narrow initial momentum
      distributions.
AB  - We investigate analytically and numerically early-time momentum diffusion rates
      for the delta-kicked rotor across the quantum to classical transition, i.e., as
      increased total system action produces more macroscopic dynamics. For
      sufficiently narrow initial momentum distributions we find a rich structure of
      resonances in these diffusion rates as a function of the effective Planck's
      constant. Our study is set in the physical context of the atom optics kicked
      rotor, and numerical simulations confirm that the resonances persist with kicks
      of finite duration and with other typical experimental imperfections, such as
      spontaneous emission noise. Our results should be testable in experiments where
      narrow initial momentum distributions are prepared using, for example, velocity
      selective Raman transitions or Bose-Einstein condensates.

PMID- 12513590
TI  - Rayleigh-Benard percolation transition of thermal convection in porous media:
      computational fluid dynamics, NMR velocity mapping, NMR temperature mapping.
AB  - Stationary thermal convection and heat conduction were studied in random-site
      percolation clusters in a Rayleigh-Benard configuration experimentally by NMR
      microscopy techniques and numerically with the aid of a finite volume method. The
      porosity of the percolation clusters, and the temperature difference applied to
      the convection cell were varied. Two-dimensional percolation networks were
      generated with the aid of a random-number algorithm. The resulting clusters were
      used as templates for the fabrication of model objects. The convective velocity
      distribution of silicon oil or ethylene glycol filled into the pore space was
      mapped and evaluated in the form of histograms. The flow patterns visualized in
      the simulated and the measured velocity maps show good coincidence. In the
      histograms, two velocity regimes can be distinguished and attributed to local
      convection rolls responsible for the low-velocity part, and cluster-spanning flow
      loops characterized by a high-velocity cut-off, respectively. The maximum
      velocity as a function of the porosity and the overall temperature difference is
      shown to be indicative for the hydro-thermodynamic Rayleigh-Benard instability
      and the geometrical percolation threshold. The coincidence of the Rayleigh-Benard
      instability (modified for porous media) and the percolation transition (modified
      for closed loops) gives rise to a new critical phenomenon termed the Rayleigh
      Benard percolation transition. It occurs at a certain combination of the porosity
      and the overall temperature difference in the cell. Temperature maps were
      recorded with the aid of a relaxation-based NMR technique. The consequence of
      different thermal conductivities in the matrix and in the fluid is that
      horizontal-temperature gradients arise even in the absence of flow. This leads to
      a superposition of uncritical convective flow driven by the horizontal
      temperature gradients whenever closed-loop pathways are possible and the critical
      Rayleigh-Benard convection based on vertical-temperature gradients.

PMID- 12513591
TI  - Decay of passive scalars under the action of single scale smooth velocity fields
      in bounded two-dimensional domains: from non-self-similar probability
      distribution functions to self-similar eigenmodes.
AB  - We examine the decay of passive scalars with small, but nonzero, diffusivity in
      bounded two-dimensional (2D) domains. The velocity fields responsible for
      advection are smooth (i.e., they have bounded gradients) and of a single large
      scale. Moreover, the scale of the velocity field is taken to be similar to the
      size of the entire domain. The importance of the initial scale of variation of
      the scalar field with respect to that of the velocity field is strongly
      emphasized. If these scales are comparable and the velocity field is time
      periodic, we see the formation of a periodic scalar eigenmode. The eigenmode is
      numerically realized by means of a deterministic 2D map on a lattice. Analytical
      justification for the eigenmode is available from theorems in the dynamo
      literature. Weakening the notion of an eigenmode to mean statistical
      stationarity, we provide numerical evidence that the eigenmode solution also
      holds for aperiodic flows (represented by random maps). Turning to the evolution
      of an initially small scale scalar field, we demonstrate the transition from an
      evolving (i.e., non-self-similar) probability distribution function (pdf) to a
      stationary (self-similar) pdf as the scale of variation of the scalar field
      progresses from being small to being comparable to that of the velocity field
      (and of the domain). Furthermore, the non-self-similar regime itself consists of
      two stages. Both stages are examined and the coupling between diffusion and the
      distribution of the finite time Lyapunov exponents is shown to be responsible for
      the pdf evolution.

PMID- 12513592
TI  - Electron-ion bremsstrahlung spectra calculations for sonoluminescence.
AB  - The bremsstrahlung spectra arising from electron-ion collisions are calculated
      for temperatures from 5000 K to 40 000 K and wavelengths from 100 nm to 1000 nm,
      for the ions He+, Ne+, Ar+, Kr+, Xe+, H+, and O+, using Hartree-Fock-Slater
      potentials. The spectral intensities are expressed in terms of Gaunt factors, the
      ratios of the present quantum computation and existing semiclassical results. For
      the heavy rare gas ions Gaunt factors of up to 3 are obtained at wavelengths of
      200 nm. We use these results to improve our calculations of rare gas
      sonoluminescence spectra [Phys. Rev. E 65, 046309 (2002)] and find that the
      improved overall sonoluminescence spectra hardly differ from our earlier results
      which were based on the semiclassical treatment of the electron-ion
      bremsstrahlung contributions. We think that in the conventional single-bubble
      sonoluminescence studies electron-ion bremsstrahlung amounts to but a small
      percentage of the overall emission. We also estimate here the effects of
      shielding of the ions due to a finite Debye length. Unless the Debye length is
      smaller than about 50 bohr, no significant influence of Debye shielding is
      discernible.

PMID- 12513593
TI  - Particle transport in a random velocity field with Lagrangian statistics.
AB  - The transport properties of a random velocity field with Kolmogorov spectrum and
      time correlations defined along Lagrangian trajectories are analyzed. The
      analysis is carried out in the limit of short correlation times, as a
      perturbation theory in the ratio, scale by scale, of the eddy decay and turnover
      time. Various quantities such as the Batchelor constant and the dimensionless
      constants entering the expression for particle relative and self-diffusion are
      given in terms of this ratio and of the Kolmogorov constant. Particular attention
      is paid to particles with finite inertia. The self-diffusion properties of a
      particle with Stokes time longer than the Kolmogorov time are determined,
      verifying on an analytical example the dimensional results of Olla [Phys. Fluids
      14, 4266 (2002)]. Expressions for the fluid velocity Lagrangian correlations and
      correlation times along a solid particle trajectory are provided in several
      parameter regimes, including the infinite Stokes time limit corresponding to
      Eulerian correlations. The concentration fluctuation spectrum and the nonergodic
      properties of a suspension of heavy particles in a turbulent flow, in the same
      regime, are analyzed. The concentration spectrum is predicted to obey, above the
      scale of eddies with lifetime equal to the Stokes time, a power law with
      universal -4/3 exponent, and to be otherwise independent of the nature of the
      turbulent flow. A preference of the solid particle to lie in less energetic
      regions of the flow is observed.

PMID- 12513594
TI  - Anticonvection with an inclined temperature gradient.
AB  - Anticonvection, caused by external heating from above in the presence of heat
      sources (or sinks) homogeneously distributed on the interface, is investigated in
      the presence of an imposed horizontal temperature gradient. Numerical finite
      difference simulations of the finite-amplitude convective regimes have been
      performed for the two-layer system of fluids. The interface is assumed to be
      flat. We discuss different scenarios of transition between multicell regimes
      characteristic of a vertical temperature gradient, and unicell structures induced
      by horizontal gradients. The coexistence of these two regimes in sufficiently
      long cavities has been obtained. Regular oscillations are also predicted in other
      situations.

PMID- 12513595
TI  - Anomalous and dimensional scaling in anisotropic turbulence.
AB  - We present a numerical study of anisotropic statistical fluctuations in
      homogeneous turbulent flows. We give a new argument to predict the dimensional
      scaling exponents, zeta(j)(d)(p)=(p+j)/3, for the projections of the pth order
      structure function in the jth sector of the rotational group. We show that the
      measured exponents are anomalous, showing a clear deviation from the dimensional
      prediction. Dimensional scaling is subleading and connected to the dynamical
      fluctuations without phase correlations. Universality of the observed anomalous
      scaling is discussed both theoretically and by means of numerical simulations at
      different Reynolds numbers and with different forcing.

PMID- 12513596
TI  - Unified lattice Boltzmann method for flow in multiscale porous media.
AB  - In this paper, we develop a unified lattice Boltzmann method for flow in
      multiscale porous media. This model not only can simulate flow in porous systems
      of various length scales but also can simulate flow in porous systems where
      multiple length scales coexist. Simulations of unidirectional steady flow through
      homogeneous and heterogeneous porous media both recover Darcy's law when the
      effects of inertial forces and Brinkman correction may be negligible. Direct use
      of this model on the usual computational nodes, with zero resistance on void
      spaces and infinite resistance on solid walls, gives results that agree well with
      analytical solutions. Simulations performed on a fractured porous system show
      that the method presented here gives very good overall permeability values for
      the whole fractured system. A series of simulations is performed on a simplified
      fractured system. The results indicate that, when the ratio of the permeability
      of the rock matrix to the fracture permeability calculated by the cubic law is
      less than 10(-4), the effects of the rock matrix flow are negligible, and the
      discrete-fracture models that ignore such flow are plausible. When the ratio is
      larger than 10(-4), the matrix flow has significant effects on the fractured
      system, and the assumption that the matrix is impermeable does not hold.
      Therefore, the use of the cubic law to calculate the fracture permeability may
      cause a significant error. It is also indicated that the larger the ratio of the
      width of the porous matrix to that of the fracture, the more significant is the
      error caused by using the cubic law.

PMID- 12513597
TI  - Rotating convection-driven dynamos at low Ekman number.
AB  - We present a fully 3D self-consistent convection-driven dynamo model with
      reference to the geodynamo. A relatively low Ekman number regime is reached, with
      the aim of investigating the dynamical behavior at low viscosity. This regime is
      computationally very demanding, which has prompted us to adopt a plane layer
      model with an inclined rotation vector, and to make use of efficiently
      parallelized code. No hyperdiffusion is used, all diffusive operators are in the
      classical form. Our model has infinite Prandtl number, a Rayleigh number that
      scales as E(-1/3) (E being the Ekman number), and a constant Roberts number. The
      optimized model allows us to study dynamos with Ekman numbers in the range [10(
      5),10(-4)]. In this regime we find strong-field dynamos where the induced
      magnetic fields satisfy Taylor's constraint to good accuracy. The solutions are
      characterized by (i) a MAC balance within the bulk, i.e., Coriolis, pressure,
      Lorentz, and buoyancy forces are of comparable magnitude, while viscous forces
      are only significant in thin boundary layers, (ii) the Elsasser number is O(10),
      (iii) the strong magnetic fields cannot prevent small-scale structures from
      becoming dominant over the large-scale components, (iv) the Taylor-Proudman
      effect is detectable, (v) the Taylorization decreases as the Ekman number is
      lowered, and (vi) the ageostrophic velocity component makes up 80% of the flow.

PMID- 12513598
TI  - Viscous dissipation for Euler's disk.
AB  - It is shown that Moffatt's recent calculation regarding the viscous dissipation
      of circulating air underneath a spinning coin overlooked the importance of the
      finite width of the viscous boundary layer. Including the enhanced dissipation in
      the boundary layer gives a larger dissipation from the moving air, and a scaling
      law of the decay of the coin's angle that is in much better accord with that
      observed. However, rolling frictional drag with the surface is an additional
      damping mechanism that could well dominate that from circulating air.

PMID- 12513599
TI  - Onset of convection in a very compressible fluid: the transient toward steady
      state.
AB  - We analyze the time profile deltaT(t) of the temperature difference, measured
      across a very compressible supercritical 3He fluid layer in its convective state.
      The experiments were done along the critical isochore in a Rayleigh-Benard cell
      after starting the vertical constant heat flow q. For q sufficiently well above
      that needed for the convection onset, the transient deltaT(t) for a given epsilon
      identical with (T-T(c))/T(c), with T(c)=3.318 K, shows a damped oscillatory
      profile with period t(osc) modulating a smooth base profile. The smooth profile
      forms the exponential tail of the transient which tends to the steady-state
      deltaT( infinity ) with a time constant tau(tail). The scaled times t(osc)/t(D)
      and tau(tail)/t(D) from all the data could be collapsed onto two curves as a
      function of the Rayleigh number over approximately 3.5 decades. Here t(D) is the
      characteristic thermal diffusion time. Furthermore, comparisons are made between
      measurements of a third characteristic time t(m) between the first peak and the
      first minimum in the deltaT(t) profile and its estimation by Onuki et al. Also,
      comparisons are made between the observed oscillations and the two-dimensional
      simulations by Onuki et al. and by Amiroudine and Zappoli. For epsilon<9 x 10(
      3), the experiments show a crossover to a different transient regime. This
      regime, which we briefly describe, is not understood at present.

PMID- 12513600
TI  - Stable two-dimensional solitary pulses in linearly coupled dissipative Kadomtsev
      Petviashvili equations.
AB  - We present a two-dimensional (2D) generalization of the stabilized Kuramoto
      Sivashinsky system, based on the Kadomtsev-Petviashvili (KP) equation including
      dissipation of the generic [Newell-Whitehead-Segel (NWS)] type and gain. The
      system directly applies to the description of gravity-capillary waves on the
      surface of a liquid layer flowing down an inclined plane, with a surfactant
      diffusing along the layer's surface. Actually, the model is quite general,
      offering a simple way to stabilize nonlinear media, combining the weakly 2D
      dispersion of the KP type with gain and NWS dissipation. Other applications are
      internal waves in multilayer fluids flowing down an inclined plane, double-front
      flames in gaseous mixtures, etc. Parallel to this weakly 2D model, we also
      introduce and study a semiphenomenological one, whose dissipative terms are
      isotropic, rather than of the NWS type, in order to check if qualitative results
      are sensitive to the exact form of the lossy terms. The models include an
      additional linear equation of the advection-diffusion type, linearly coupled to
      the main KP-NWS equation. The extra equation provides for stability of the zero
      background in the system, thus opening a way for the existence of stable
      localized pulses. We focus on the most interesting case, when the dispersive part
      of the system is of the KP-I type, which corresponds, e.g., to capillary waves,
      and makes the existence of completely localized 2D pulses possible. Treating the
      losses and gain as small perturbations and making use of the balance equation for
      the field momentum, we find that the equilibrium between the gain and losses may
      select two steady-state solitons from their continuous family existing in the
      absence of the dissipative terms (the latter family is found in an exact
      analytical form, and is numerically demonstrated to be stable). The selected
      soliton with the larger amplitude is expected to be stable. Direct simulations
      completely corroborate the analytical predictions, for both the physical and
      phenomenological models.

PMID- 12513601
TI  - Calculated sheath dynamics under the influence of an asymmetrically pulsed dc
      bias.
AB  - A one-dimensional model is used to describe the evolution of charged particles in
      a plasma sheath driven by an asymmetrically pulsed dc bias in the frequency range
      of 100 kHz to 10 MHz. The temporal-spatial evolution of the sheath is obtained
      through the simultaneous solution of Poisson's equations, the ionic fluid
      equations and a Boltzmann treatment of the electrons. Calculations are performed
      to demonstrate the effects ionic inertia and sheath restructuring have on the
      temporal dependence of current and energy of the ions arriving at the driven
      electrode. The temporal scale is observed to depend on the bulk density of the
      plasma. The pulse frequency, the pulse duty, and the capacitive coupling of the
      pulse to the driving electrode are varied to demonstrate the influence of these
      factors on the energy distribution of the ions extracted from the plasma to the
      electrode.

PMID- 12513602
TI  - Charge-exchange-induced two-electron satellite transitions from autoionizing
      levels in dense plasmas.
AB  - Order-of-magnitude anomalously high intensities for two-electron (dielectronic)
      satellite transitions, originating from the He-like 2s(2) 1S0 and Li-like 1s2s(2)
      (2)S(1/2) autoionizing states of silicon, have been observed in dense laser
      produced plasmas at different laboratories. Spatially resolved, high-resolution
      spectra and plasma images show that these effects are correlated with an intense
      emission of the He-like 1s3p 1P-1s(2) 1S lines, as well as the K(alpha) lines. A
      time-dependent, collisional-radiative model, allowing for non-Maxwellian electron
      energy distributions, has been developed for the determination of the relevant
      nonequilibrium level populations of the silicon ions, and a detailed analysis of
      the experimental data has been carried out. Taking into account electron density
      and temperature variations, plasma optical-depth effects, and hot-electron
      distributions, the spectral simulations are found to be not in agreement with the
      observations. We propose that highly stripped target ions (e.g., bare nuclei or H
      like 1s ground-state ions) are transported into the dense, cold plasma
      (predominantly consisting of L- and M-shell ions) near the target surface and
      undergo single- and double-electron charge-transfer processes. The spectral
      simulations indicate that, in dense and optically thick plasmas, these charge
      transfer processes may lead to an enhancement of the intensities of the two
      electron transitions by up to a factor of 10 relative to those of the other
      emission lines, in agreement with the spectral observations.

PMID- 12513603
TI  - Implosion of multilayered cylindrical targets driven by intense heavy ion beams.
AB  - An analytical model for the implosion of a multilayered cylindrical target driven
      by an intense heavy ion beam has been developed. The target is composed of a
      cylinder of frozen hydrogen or deuterium, which is enclosed in a thick shell of
      solid lead. This target has been designed for future high-energy-density matter
      experiments to be carried out at the Gesellschaft fur Schwerionenforschung,
      Darmstadt. The model describes the implosion dynamics including the motion of the
      incident shock and the first reflected shock and allows for calculation of the
      physical conditions of the hydrogen at stagnation. The model predicts that the
      conditions of the compressed hydrogen are not sensitive to significant variations
      in target and beam parameters. These predictions are confirmed by one-dimensional
      numerical simulations and thus allow for a robust target design.

PMID- 12513604
TI  - Static configurations of gravitating dusty plasmas.
AB  - Plasma and dust are key ingredients of the universe, and in larger astrophysical
      systems the gravitational and electrostatic forces can become comparable, thus
      prompting a careful revision of stationary configurations of self-gravitating
      dusty plasmas. An overview of some physically acceptable models is given, with
      applications to relevant structures in space and astrophysical plasmas. For those
      cases where explicit solutions can be obtained, the scales over which the system
      is inhomogeneous are of the order of the Jeans lengths, determined in the usual
      way by studying local perturbations of a uniform equilibrium.

PMID- 12513605
TI  - Effect of the electron gas polarizability on the specific heat of phonons in
      Coulomb crystals.
AB  - The effect of the background polarizability on the thermodynamic properties of a
      Coulomb crystal of ions is studied. The response of electrons is treated using
      the Thomas-Fermi (TF) and random phase approximations (RPA). For the case of ions
      fixed at their lattice sites, the energy of bcc and fcc crystals is calculated to
      first order in the screening parameter (kappa(TF)a)(2) (kappa(TF) is the TF wave
      number and a is the ion sphere radius). It is shown that in the RPA there exist
      domains of parameters (mass density rho and charge number Z) where energy of fcc
      crystal is lower than that of bcc. The effect of ion vibrations is studied using
      harmonic lattice approximation. It is shown that phonon modes are nearly
      identical in the RPA and in the TF approximation. The latter allows one to apply
      the Ewald technique to the construction of the dynamical matrix, which speeds up
      all calculations considerably. The main thermodynamic quantities of phonons are
      calculated as functions of the quantum parameter T(p)/T (where T(p) is the ion
      plasma temperature) and the screening parameter. The electron polarizability
      leads to a moderate increase of the phonon thermodynamic quantities as compared
      to the case of one-component plasma with rigid background (by approximately 30%
      at kappa(TF)a=0.8). Zero-point motion of ions modifies the aforementioned domains
      where fcc has lower energy than bcc for static ions. The effect is profound at
      small Z but leaves the domains unaltered at larger Z. The thermal vibrations of
      ions at T greater, similar T(p) eliminate completely the domains where fcc is
      thermodynamically preferable at T=0. The related model of Yukawa-Wigner solid is
      briefly studied. It is shown that neither bcc nor fcc crystal structures are
      stable in this model.

PMID- 12513606
TI  - Photon acceleration of ultrashort laser pulses by relativistic ionization fronts.
AB  - We present experimental results from the collision of weak ultrashort pulses with
      relativistic ionization fronts in copropagation and counterpropagation. The
      observed frequency upshifts of the probe pulses provide not only information
      about the electron density of the ionization front but also reveal the fine
      structure of the front. The connection between the correlation lengths for
      copropagation and counterpropagation and the longitudinal and transverse
      dimensions of the ionization front is also demonstrated thus showing the
      feasibility of using the frequency upshift experienced by short probe pulses to
      fully characterize relativistic ionization fronts and other relativistic coherent
      structures in laser-produced plasmas.

PMID- 12513607
TI  - Diffusion in two-temperature thermal plasmas.
AB  - Combined diffusion coefficients, which allow species to be grouped into their
      parent gases, are derived in a thermal plasma in which the kinetic temperature of
      the electrons is different from that of the heavy species. As in previous
      calculations of combined diffusion coefficients for a one-temperature plasma,
      chemical equilibrium is assumed, and a plasma in a mixture of two homonuclear
      nonreacting gases is treated. Expressions for ambipolar diffusion in a two
      temperature plasma are derived. Coupling between the electrons and the heavy
      species is retained in the calculations. It is confirmed that the values of the
      diffusion coefficients are consistent with mass conservation, in contrast to
      previous calculations that were based on a theory in which the electrons and
      heavy species were decoupled. Illustrative results are presented for a thermal
      plasma in different mixtures of argon and hydrogen at 1 bar, for temperatures up
      to 25 000 K and different ratios of electron to heavy species temperature.

PMID- 12513608
TI  - Nonlinear features of two-plasmon decay in a long-scale-length plasma.
AB  - A transparent model of two-plasmon decay in a spatially homogeneous or long-scale
      length plasma, reproducing the main experimentally observed nonlinear features,
      is presented. Secondary coupling between the plasma waves and the ion-acoustic
      waves, including their frequency mismatch, proves to be the principal saturation
      mechanism of the instability. The wave amplitude time evolution and spectra as
      well as the hot-electron generation properties are compared to the experimental
      data.

PMID- 12513609
TI  - Stochastic diffusion of ions due to a finite set of lower hybrid waves.
AB  - In this paper we generalize the discussion on stochastic diffusion of energetic
      ions by lower hybrid waves by considering a case where a set of waves with
      similar frequencies is present in the system. In the particular case of a finite
      number of coherent waves, we show that the threshold for stochastic diffusion is
      reduced in comparison with the threshold in the one-wave case, and that the
      ensuing particle diffusion in velocity space occurs in periodic bursts along the
      time evolution. In the more general case of a set of waves with random phases, we
      have obtained even more efficient long-term diffusion in velocity space, for the
      same number of waves, although the initial diffusion rate can be smaller than in
      the case of coherent waves.

PMID- 12513610
TI  - Symmetry transforms for ideal magnetohydrodynamics equilibria.
AB  - A method for constructing ideal magnetohydrodynamics (MHD) equilibria is
      introduced. The method consists of the application of symmetry transforms to any
      known MHD equilibrium [ O. I. Bogoyavlenskij, Phys. Rev. E. 62, 8616, (2000)].
      The transforms break the geometrical symmetries of the field-aligned solutions
      and produce continuous families of the nonsymmetric MHD equilibria. The method of
      symmetry transforms also allows to obtain MHD equilibria with current sheets and
      exact solutions with noncollinear vector fields B and V. A model of the
      nonsymmetric astrophysical jets outside of their accretion disks is developed.
      The total magnetic and kinetic energy of the jet is finite in any layer
      c(1)<z<c(2). The jet possesses current sheets and is highly collimated in view of
      a rapid decrease of the magnetic field B in the transverse direction. The method
      gives also the MHD equilibria that model ball lightning with dynamics of plasma
      inside the fireball.

PMID- 12513611
TI  - Complex-plasma boundaries.
AB  - This study deals with the boundary between a normal plasma of ions and electrons,
      and an adjacent complex plasma of ions, electrons, and microparticles, as found
      in innumerable examples in nature. Here we show that the matching between the two
      plasmas involve electrostatic double layers. These double layers explain the
      sharp boundaries observed in the laboratory and in astrophysics. A modified
      theory is derived for the double layers that form at the discontinuity between
      two different complex plasmas and at the point of contact of three complex
      plasmas. The theory is applied to the first measurements from the Plasma Kristall
      Experiment (PKE) Nefedov Laboratory in the International Space Station.

PMID- 12513612
TI  - Electrical conductivity of hot expanded aluminum: experimental measurements and
      ab initio calculations.
AB  - Experimental measurements and theoretical calculations of the electrical
      conductivity of aluminum are presented in the strongly coupled partially
      degenerate regime (rho=0.3 g/cm(3), 5000<T<15 000 K). The experiments were
      performed in an isochoric plasma closed vessel designed to confine electrical
      plasma discharges up to 1.5 GPa. Aluminum properties were determined
      theoretically by ab initio molecular dynamics simulations in the local density
      approximation, from which the conductivity was computed using the Kubo-Greenwood
      formula. The theoretical results were validated in the dense coupled regime
      against previously published experimental results and then applied to our
      experimental low density regime, showing that the theoretical results
      overestimate the experimental conductivities.

PMID- 12513613
TI  - Resistive wall impedance and tune shift for a chamber with a finite thickness.
AB  - Since the resistive wall impedance for a beam pipe of a nonround cross section
      depends on the coordinates of a witness particle, the witness particle receives
      an incoherent tune shift. When the expression for the impedance of an infinitely
      thick chamber is applied to the calculation of this tune shift, it becomes
      infinite. We have derived the resistive wall impedance for a chamber with a
      finite thickness and calculated the tune shift. There is no ambiguity in this
      expression for the tune shift, because it is automatically finite.

PMID- 12513614
TI  - Free-electron-laser oscillator with a linear taper.
AB  - We present experiments and simulations showing the behavior of a free-electron
      laser (FEL) with both positive and negative linear tapers along the wiggler. We
      show the power desynchronism curve widths, efficiency, exhaust electron energy
      spread, and wavelength dependence as a function of taper for 3- and 6-microm
      optical wavelengths and for resonators with 10% and 2% loss/pass. Simulations of
      the experiments, using a multimode analysis, are seen to be in general agreement
      with the experimental results, carried out at the IR Demo FEL at Thomas Jefferson
      National Accelerator Facility. We find that short-pulse effects are more
      effective than tapers in producing high efficiency with low exhaust energy
      spread, and the expected performance enhancement of FEL tapering is not achieved.

PMID- 12513615
TI  - Self-consistent nonstationary processes in phase-mixed electron beams focused by
      mobile ions.
AB  - This paper is devoted to the analysis of nonstationary self-consistent processes
      in electron beam propagation in the presence of mobile ions. This problem is of
      particular interest for the recently developed plasma-assisted slow-wave
      oscillators (pasotrons). In pasotrons beam focusing is provided by ions (in
      contrast to other high-power microwave sources where the beam is focused by a
      strong external magnetic field). Typically, pasotrons operate in rather long
      pulses with a pulse duration on the order of 100 micros and larger. In such a
      time scale, the ion motion can play a significant role, and therefore, the self
      consistent nonstationary processes in the beam transport and ion motion become
      important. In particular, the interaction with beam electrons may result in ion
      axial acceleration. In the present paper, a theory that describes these
      nonstationary self-consistent processes is developed, taking account of the phase
      mixing of electrons having a spread in their initial transverse velocities. The
      paper also contains some simulation results obtained for typical pasotron
      parameters.

PMID- 12513616
TI  - Generation and growth rates of nonlinear distortions in a traveling wave tube.
AB  - The structure of a steady state multifrequency model of a traveling wave tube
      amplifier is exploited to describe the generation of intermodulation frequencies
      and calculate their growth rates. The model describes the evolution of Fourier
      coefficients of circuit and electron beam quantities and has the form of
      differential equations with quadratic nonlinearities. Intermodulation frequencies
      are sequentially generated by the quadratic nonlinearities in a series solution
      of the differential equations. A formula for maximum intermodulation growth rates
      is derived and compared to simulation results.

PMID- 12513617
TI  - Superluminal effects and negative group delays in electronics, and their
      applications.
AB  - The causality principle does not forbid negative group delays of analytic signals
      in electronic circuits; in particular, the peak of a pulse can leave the exit
      port of a circuit before it enters the input port. Furthermore, pulse distortion
      for these "superluminal" analytic signals can be negligible in both the optical
      and electronic domains. Here we suggest a possible extension of these ideas to
      microelectronics. The underlying principle is that negative feedback can be used
      to produce negative group delays. Such negative group delays can be used to
      cancel out the positive group delays introduced by transistor latency, as well as
      the propagation delays due to the interconnections between transistors. Using
      this principle, it may be possible to speed up computer systems.

PMID- 12513618
TI  - Defining the Fresnel zone for broadband radiation.
AB  - The concept of the Fresnel zone is central to many areas of imaging. In
      tomographic imaging, the transverse spatial resolution can be limited by the size
      of the first Fresnel zone, usually defined only for monochromatic radiation. With
      the increasing prevalence of broadband tomographic imaging systems, a
      generalization of this concept is required. Here, a proposed generalization is
      described in the context of femtosecond optics, and experimentally verified using
      terahertz time-domain spectroscopy. Based on this definition, a simple zone plate
      design is demonstrated.

PMID- 12513619
TI  - Breathers in a discrete nonlinear Schrodinger-type model: Exact stability
      results.
AB  - Following our earlier work [Phys. Rev. Lett. 84, 3570 (2000)] we present an exact
      linear stability analysis of one-site monochromatic breathers in a piecewise
      smooth discrete nonlinear Schrodinger-type model. Destabilization of the breather
      occurs by virtue of a growth rate becoming positive as a stability border is
      crossed, while above a critical spatial decay rate (lambda(c)) the breather is
      found to be intrinsically unstable. The model admits of other exact breather
      solutions, including multisite monochromatic breathers for which the profile
      variable (phi(n)) crosses a relevant threshold at more than one site. In
      particular, we consider exact two-site breather solutions with phase difference
      delta between the two sites above threshold, and present stability results for
      delta=pi (antiphase breather; the in-phase breather with delta=0 happens to be
      intrinsically unstable). We obtain a band of extended eigenmodes, together with a
      pair of localized symmetric modes and another pair of localized antisymmetric
      ones. The frequencies of the localized modes vary as the parameters
      characterizing the breather are made to vary, and destabilization occurs through
      the Krein collision of a quartet of growth rates, leading to temporal growth of a
      pair of symmetric eigenmodes of nonzero frequency. We clarify the limit N-->
      infinity (N is the gap length between the sites above threshold) when the two
      site breather reduces to a pair of decoupled one-site breathers. The model offers
      the possibility of obtaining spatially random vortex-type breathers.

PMID- 12513620
TI  - Cylinder gratings in conical incidence with applications to modes of air-cored
      photonic crystal fibers.
AB  - We develop a formulation for cylinder gratings in conical incidence, using a
      multipole method. The theory, and its numerical implementation, is applied to two
      dimensional photonic crystals consisting of a stack of one-dimensional gratings,
      each characterized by its plane wave scattering matrix. These matrices are used
      in combination with Bloch's theorem to determine the band structure of the
      photonic crystal from the solution of an eigenvalue problem. We show that the
      theory is well adapted to the difficult task of locating the complete band gaps
      needed to support air-guided modes in microstructured optical fibers, that is,
      optical fibers in which the confinement of light in a central air hole is
      achieved by photonic band-gap effects in a periodic cladding comprising a lattice
      of air holes in a glass matrix.

PMID- 12513621
TI  - Coherence properties of the parametric three-wave interaction driven from an
      incoherent pump.
AB  - We consider the basic problem of the parametric generation process from an
      incoherent pump wave. The analysis of the degenerate configuration of the two
      wave interaction reveals that the mutual convection (i.e., group-velocity
      difference) between the incoherent pump and the signal (i.e., the daughter wave)
      may quench their parametric interaction, so that the gain experienced by the
      signal may become arbitrarily small. Conversely, in the absence of convection,
      the incoherent pump efficiently amplifies the signal wave, although this
      amplification process cannot lead to the generation of a coherent signal.
      However, in the case of nondegenerate three-wave interaction, we show the
      existence of a convection-induced phase-locking mechanism in which the
      incoherence of the pump is absorbed by the idler wave allowing the signal wave to
      grow efficiently with a high degree of coherence. We calculate explicitly the
      autocorrelation function of the generated signal in this regime of coherent
      incoherent interaction. The analysis reveals that, owing to the convection
      induced averaging process that accompanies the phase-locking mechanism, the
      degree of coherence of the signal increases as the degree of coherence of the
      pump decreases. We establish the experimental conditions that would allow for the
      observation of the transition between the incoherent and the coherent regimes of
      the three-wave parametric interaction.

PMID- 12513622
TI  - Coexistence of a self-induced transparency soliton and a Bragg soliton.
AB  - We theoretically show that a self-induced transparency (SIT) soliton and a Bragg
      soliton can coexist in a nonlinear photonic band gap (PBG) medium doped uniformly
      with inhomogeneous-broadening two-level atoms. The Maxwell-Bloch equations for
      the pulse propagating through such a uniformly doped PBG structure are derived
      first and further reduced to an effective nonlinear Schrodinger equation. This
      model describes an equivalent physical mechanism for a Bragg-soliton propagation
      resulting from the effective quadratic dispersion balancing with the effective
      third-order nonlinearity. Because the resonant atoms are taken into account, the
      original band gap can be shifted both by the dopants and the instantaneous
      nonlinearity response originating from an intense optical pulse. As a result,
      even if a SIT soliton with its central frequency deep inside the original
      forbidden band, it still can propagate through the resonant PBG medium as long as
      this SIT soliton satisfies the effective Bragg-soliton propagation. An
      approximate soliton solution describing such coexistence is found. We also show
      that the pulse width and group velocity of this soliton solution can be uniquely
      determined for given material parameters, atomic transition frequency, and input
      central frequency of the soliton. The numerical examples of the SIT soliton in a
      one-dimensional As2S3-based PBG structure doped uniformly with Lorentzian line
      shape resonant atoms are shown. It is found that a SIT soliton with approximately
      100-ps width in such a resonant PBG structure can travel with the velocity being
      two orders of magnitude slower than the light speed in an unprocessed host
      medium.

PMID- 12513623
TI  - Pulse dynamics in actively mode-locked lasers with frequency shifting.
AB  - The dynamics of wave packet splitting in a dissipative Schrodinger-like dynamical
      system is theoretically studied by considering the model of an amplitude
      modulated mode-locked laser with frequency shifting provided by an intracavity
      frequency modulation. It is shown that as the strength of the frequency
      modulation is increased, a bifurcation takes place which corresponds to a
      transition from a single-pulse steady-state oscillation to a two-pulse coherent
      oscillatory dynamics. An analytical model for pulse splitting bifurcation and
      onset of two-mode oscillatory dynamics, based on a Gaussian pulse analysis, is
      presented and compared with numerical simulations.

PMID- 12513624
TI  - High-power regime of femtosecond-laser pulse propagation in silica: multiple-cone
      formation.
AB  - We present a numerical study of the (2+1)-dimensional propagation dynamics of
      femtosecond-laser pulses in silica. In particular, considered are pulses, whose
      power is tens to hundreds of times higher than the threshold for self-focusing.
      We solve the axially symmetric, extended, nonlinear Schrodinger equation for the
      laser electric field, including group velocity dispersion, Kerr nonlinearity,
      plasma formation and defocusing, self-steepening, and space-time focusing. Our
      simulation results reveal that the high-power pulses are split spatially, as well
      as temporally, several times into multiple cones during its propagation. This new
      structure is formed as a result of the interplay of strong Kerr self-focusing and
      plasma defocusing. The number of cones and their angle with respect to the
      propagation axis increase with incident pulse energy. The uncertainty, which may
      be contained in the evaluation of plasma response and band-to-band transition
      rate, and the pulse disturbance by modulation instability are also analyzed.
      Although these influence the details of the pulse propagation, they do not affect
      the essence of our results: the multiple-cone formation.

PMID- 12513625
TI  - Omnidirectional elastic band gap in finite lamellar structures.
AB  - This paper presents a comprehensive theoretical analysis of the occurrence of
      omnidirectional reflection in one-dimensional phononic crystal structures. We
      discuss the conditions for a one-dimensional layered structure, made of elastic
      materials, to exhibit total reflection of acoustic incident waves in a given
      frequency range, for all incident angles and all polarizations. The property of
      omnidirectional reflection can be fulfilled with a simple finite superlattice if
      the substrate from which the incident waves are launched is made of a material
      with high acoustic velocities (this is very similar to the case of
      omnidirectional optical mirror where the incident light is generated in vacuum).
      However, if the substrate is made of a material with low acoustic velocities, we
      propose two solutions to obtain an omnidirectional band gap, namely, the cladding
      of a superlattice with a layer of high acoustic velocities, which acts like a
      barrier for the propagation of phonons, or the association in tandem of two
      different superlattices in such a way that the superposition of their band
      structures exhibits an absolute acoustic band gap. We discuss the appropriate
      choices of the material and geometrical properties to realize such structures.
      The behavior of the transmission coefficients are discussed in relation with the
      dispersion curves of the finite structure embedded between two substrates. Both
      transmission coefficients and densities of states (from which we derive the
      dispersion curves) are calculated in the framework of a Green's function method.

PMID- 12513626
TI  - Measurement of the magneto-optical correlation length in turbid media.
AB  - In multiple light scattering media, magnetic field induced circular birefringence
      (Faraday effect) influences interference effects such as speckle pattern or
      coherent backscattering. It was predicted that in the diffusive regime the
      relevant correlation length with respect to the Faraday rotation l( small star,
      filled )(F) differs, in general, from the transport mean free path l( small star,
      filled ). We have experimentally verified the prediction that the ratio l( small
      star, filled )(F)/l( small star, filled ) equals 2 for Rayleigh scattering and
      decreases to 1 with increasing scatterer size. We also discuss the influence of
      the structure factor on l( small star, filled )(F).

PMID- 12513627
TI  - Experimental demonstration of realizability of optical focus wave modes.
AB  - The homogeneous scalar wave equation has a number of so-called localized wave
      (LW) solutions, instantaneous, Gaussian pulselike intensity distribution of which
      propagates without any spread or distortions in free space. Despite the
      undoubtedly intriguing properties and considerable effort that has been made to
      implement such wave fields, in the optical domain only their limiting case-the so
      called Bessel-X pulses-has been experimentally launched so far. In this paper we
      report on experimental evidence of the optical realizability of the "fundamental"
      special case of the LW's-the focus wave modes.

PMID- 12513628
TI  - Temperature-controlled random laser action in liquid crystal infiltrated systems.
AB  - We study an amplifying disordered dielectric material of which the scattering
      strength can be controlled externally via temperature. Such a system was realized
      by infiltrating liquid crystal and laser dye inside sintered glass powders. The
      random laser materials that were obtained this way can be brought below or above
      threshold by small changes in environment temperature, and the bandwidth of its
      emission can be tuned. We will go into the experimental details and the technical
      aspects of the realization of these systems, and show measurements on the
      diffusion constant and spectral properties of the emission.

PMID- 12513629
TI  - Dipolar effects on soliton dynamics on a discrete ferromagnetic chain.
AB  - The contributions of dipole-dipole interactions to the dynamics of solitons on a
      one-dimensional discrete easy-plane Heisenberg ferromagnet, in which the
      biquadratic exchange interactions are taken into account in addition to the
      Zeeman energy, the uniaxial anisotropy, and the exchange energy, are studied
      numerically. The results of a numerical simulation of the dynamics of a single
      soliton, as well as collision between a soliton-antisoliton pair, indicated that
      the energy-velocity curves for the solitons in the ferromagnetic chain present
      the signature of five different branches corresponding to different types of
      nonlinear elementary excitations in the chain.

PMID- 12513630
TI  - Hydrogen atom in the presence of uniform magnetic and quadrupolar electric
      fields: integrability, bifurcations, and chaotic behavior.
AB  - We investigate the classical dynamics of a hydrogen atom in the presence of
      uniform magnetic and quadrupolar electric fields. After some reductions, the
      system is described by a two degree of freedom Hamiltonian depending on two
      parameters. On the one hand, it depends on the z component of the canonical
      angular momentum P(phi), which is an integral because the system is axially
      symmetric; and on the other it also depends on a parameter representing the
      relative field strengths. We note that this Hamiltonian is closely related to the
      one describing the generalized van der Waals interaction. We report three cases
      of integrability. The structure and evolution of the phase space are explored
      intensively by means of Poincare surfaces of section when the parameters vary. In
      this sense, we find several bifurcations that strongly change the phase space
      structure. The chaotic behavior of the system is studied and three order-chaos
      transitions are found when the system passes through the integrable cases.
      Finally, the ionization mechanics is studied.

PMID- 12513631
TI  - Efficient Brownian dynamics simulation of particles near walls. I. Reflecting and
      absorbing walls.
AB  - In this paper a method of numerically handling boundary conditions within
      Brownian dynamics simulations is discussed. The usual naive treatment of
      identifying reflection or absorption processes by checking for boundary crossings
      yields O(sqrt[deltat]) discretization errors. The method we propose here yields
      O(deltat) errors, similar to the case of Brownian dynamics without wall
      interaction. The main idea is to ensure that the zeroth (in the case of
      absorption), first, and second moments of the particle's displacement steps are
      correct up to order deltat. To fulfill this requirement near a wall, one has to
      include nontrivial corrections, because the stochastic contribution does not
      average out when the distance to the wall is of the order of the step length. We
      demonstrate here that the method substantially reduces the discretization error
      for the simple cases of an absorbing and a reflecting wall. Our method comprises
      an improvement over earlier methods proposed by Lamm and Schulten [J. Chem. Phys.
      78, 2713 (1983)] and Ottinger [J. Chem. Phys. 91, 6455 (1937)]. Their methods
      heavily depend on full, explicit, analytical expressions for solutions of the
      diffusion equation near a wall, which they use to make a correction after a
      stochastic step has been made. Our method only involves the, usually much
      simpler, lowest moments (up to the second) of the probability density
      distributions for the displacement of the particle in one time step. This means
      the method only uses the initial particle position to determine a valid step, and
      there is no need for corrections afterwards. Because much less information is
      needed (three moments instead of full probability densities), in many cases
      information can be stored simply in interpolation functions and there is no need
      to evaluate complicated analytical expressions at every time step. This makes the
      method more efficient and easy to generalize to other situations than the
      relatively simple case of a flat wall. Moreover, because analytic expressions are
      not needed, other methods to determine the needed moments can be used. This makes
      our method much more flexible.

PMID- 12513632
TI  - Efficient Brownian dynamics simulation of particles near walls. II. Sticky walls.
AB  - In this paper we treat a boundary condition, the "sticky boundary," which appears
      to be quite useful in mesoscopic models. The sticky boundary is modeled as an
      infinitely deep, infinitely narrow, potential well adjacent to a reflecting
      boundary. The free energy corresponding to this boundary is finite. The boundary
      condition, which can be viewed as an intermediate between the absorbing and
      reflecting boundary condition, may have many applications, e.g., for the
      simulation of the partial adsorption of polymer molecules to walls and for the
      modeling of solvent quality. We will derive an efficient Brownian dynamics
      algorithm, capable of handling interactions of a diffusing particle with a sticky
      wall. Our approach avoids the large discretization errors that occur in the
      simulation of boundary interactions within the "standard" Brownian dynamics
      approach. The essence of our method was presented before [E. Peters and T.
      Barenbrug, Phys. Rev. E (to be published)]. The treatment of the wall as proposed
      here is quite general, and therefore not limited to the use within Brownian
      dynamics. In other simulation techniques which aim at treating the dynamics of
      mesoscopic particles near walls, we expect it to be of use as well.

PMID- 12513633
TI  - Generalization of the Wang-Landau method for off-lattice simulations.
AB  - We present a rigorous derivation for off-lattice implementations of the so-called
      "random-walk" algorithm recently introduced by Wang and Landau [Phys. Rev. Lett.
      86, 2050 (2001)]. Originally developed for discrete systems, the algorithm
      samples configurations according to their inverse density of states using Monte
      Carlo moves; the estimate for the density of states is refined at each simulation
      step and is ultimately used to calculate thermodynamic properties. We present an
      implementation for atomic systems based on a rigorous separation of kinetic and
      configurational contributions to the density of states. By constructing a
      "uniform" ensemble for configurational degrees of freedom-in which all potential
      energies, volumes, and numbers of particles are equally probable-we establish a
      framework for the correct implementation of simulation acceptance criteria and
      calculation of thermodynamic averages in the continuum case. To demonstrate the
      generality of our approach, we perform sample calculations for the Lennard-Jones
      fluid using two implementation variants and in both cases find good agreement
      with established literature values for the vapor-liquid coexistence locus.

PMID- 12513634
TI  - First- and last-passage Monte Carlo algorithms for the charge density
      distribution on a conducting surface.
AB  - Recent research shows that Monte Carlo diffusion methods are often the most
      efficient algorithms for solving certain elliptic boundary value problems. In
      this paper, we extend this research by providing two efficient algorithms based
      on the concept of "last-passage diffusion." These algorithms are qualitatively
      compared with each other (and with the best first-passage diffusion algorithm) in
      solving the classical problem of computing the charge distribution on a
      conducting disk held at unit voltage. All three algorithms show detailed
      agreement with the known analytic solution to this problem.

PMID- 12513635
TI  - Coarse-grained loop algorithms for Monte Carlo simulation of quantum spin
      systems.
AB  - Recently, Syljuasen and Sandvik [Phys. Rev. E. (to be published)] proposed a new
      framework for constructing algorithms of quantum Monte Carlo simulation. While it
      includes new classes of powerful algorithms, it is not straightforward to find an
      efficient algorithm for a given model. Based on their framework, we propose an
      algorithm that is a natural extension of the conventional loop algorithm with the
      split-spin representation. A complete table of the vertex density and the worm
      scattering probability is presented for the general XXZ model of an arbitrary S
      with a uniform magnetic field.

PMID- 12513636
TI  - Sweeny and Gliozzi dynamics for simulations of Potts models in the Fortuin
      Kasteleyn representation.
AB  - We compare the correlation times of the Sweeny and Gliozzi dynamics for two
      dimensional Ising and three-state Potts models, and the three-dimensional Ising
      model for the simulations in the percolation representation. The results are also
      compared with Swendsen-Wang and Wolff cluster dynamics. It is found that Sweeny
      and Gliozzi dynamics have essentially the same dynamical critical behavior.
      Contrary to Gliozzi's claim [Phys. Rev. E 66, 016115 (2002)], the Gliozzi
      dynamics has critical slowing down comparable to that of other cluster methods.
      For the two-dimensional Ising model, both Sweeny and Gliozzi dynamics give good
      fits to logarithmic size dependences for the correlation times; for two
      dimensional three-state Potts model, their dynamical critical exponent z is
      0.49+/-0.01; the three-dimensional Ising model has z=0.37+/-0.02.

PMID- 12513637
TI  - Dynamical mean-field approximation for a pair contact process with a particle
      source.
AB  - The one-dimensional pair contact process with a particle source is studied by
      using dynamical cluster mean-field approximations with sites up to n=12. The
      results obtained for different levels of approximation become convergent
      especially for n>or=6 and allow us to derive reliable extrapolations to the limit
      n--> infinity. At the zero source limit, the critical point exhibits a
      discontinuity whose magnitude vanishes with 1/n. Coherent anomaly analysis of the
      data supports the conclusion that the vanishing of the order parameter and the
      density of isolated particles have the same critical behavior. In contrast to an
      earlier prediction, the present approximation does not support the existence of
      critical behavior in the inactive phase where the frozen density of isolated
      particles depends on the initial state.

PMID- 12513638
TI  - Simplified transfer matrix approach in the two-dimensional Ising model with
      various boundary conditions.
AB  - A recent simplified transfer matrix solution of the two-dimensional Ising model
      on a square lattice with periodic boundary conditions is generalized to periodic
      antiperiodic, antiperiodic-periodic, and antiperiodic-antiperiodic boundary
      conditions. It is suggested to employ linear combinations of the resulting
      partition functions to investigate finite-size scaling. An exact relation of such
      a combination to the partition function corresponding to Brascamp-Kunz boundary
      conditions is found.

PMID- 12513639
TI  - Wealth distribution in an ancient Egyptian society.
AB  - Modern excavations yielded a distribution of the house areas in the ancient
      Egyptian city Akhetaten, which was populated for a short period during the 14th
      century B.C. Assuming that the house area has a power law dependence of the
      wealth of its inhabitants allows us to make a comparison of the wealth
      distributions in ancient and modern societies.

PMID- 12513640
TI  - Chaotic dynamics of an air-damped bouncing ball.
AB  - A ball bouncing elastically upon a vertically vibrated platform is one of the
      simplest examples of a chaotic system. If dissipation is introduced at each
      bounce through a coefficient of restitution, the motion is no longer chaotic; the
      trajectories exhibit locking solutions that result in periodic behavior. Here we
      investigate the dynamics of a bouncing ball influenced by air damping. We
      consider the effects of both static air and air moving with the platform, and
      show that there is an exact mapping between them. In either case, the system has
      a rather complex dynamical behavior including truly chaotic trajectories. Our
      results highlight the importance of air effects for fine particulate systems.

PMID- 12513641
TI  - Detection and classification of nonlinear dynamic switching events.
AB  - A method is proposed for detecting chaotic switching events. Switching events are
      classified by the time of the event and by parameter value. Classifications are
      based on the density of localized dynamics about a test trajectory. This method
      is shown to be successful in tracking short-time parameter modulation and
      hyperchaotic key shifting used in otherwise secure communications.

PMID- 12513642
TI  - Bifurcation diversity of dynamic thermocapillary liquid layers.
AB  - We study, from the theoretical point of view, instabilities appearing in a liquid
      layer, where a dynamic flow is imposed through a nonzero temperature gradient at
      the bottom. Experimentally many interesting dynamical behaviors have been
      discovered in this system. In this Brief Report we prove that the basic solution
      can display great richness of bifurcations which are controlled by heat related
      parameters. Different kinds of spatially extended and localized structures
      appear, which are both stationary or oscillatory. These last ones can present
      amazing patterns such as squares or spirals. Also competing solutions at
      codimension-two bifurcation points have been found: stationary radial rolls with
      different wave numbers, radial rolls with hydrothermal waves, and hydrothermal
      waves with different wave numbers. Remarkably our results recover many features
      of numerous reported experiments, predict new instabilities, and by giving a
      deeper insight into how physical parameters contribute to bifurcations, open a
      gateway to control those instabilities.

PMID- 12513643
TI  - Propagation of linear waves in relativistic anisotropic magnetohydrodynamics.
AB  - Gedalin [Phys. Rev. E 47, 4354 (1993)] derived a dispersion relation for linear
      waves in relativistic anisotropic Magnetohydrodynamics (MHD). This dispersion
      relation is used to point out the regions where the relativistic anisotropic MHD
      leads to new results that cannot be obtained using usual collisional relativistic
      MHD. This is highlighted by plotting a Fresnal ray surface. Conditions for the
      onset of firehose and mirror instabilities are also indicated. Such a study can
      be applied to astrophysical features such as pulsar winds, propagation of cosmic
      rays, etc.

PMID- 12513644
TI  - Parallel-in-time molecular-dynamics simulations.
AB  - While there have been many progress in the field of multiscale simulations in the
      space domain, in particular, due to efficient parallelization techniques, much
      less is known in the way to perform similar approaches in the time domain. In
      this paper we show on two examples that, provided we can describe in a rough but
      still accurate way the system under consideration, it is indeed possible to
      parallelize molecular dynamics simulations in time by using the recently
      introduced pararealalgorithm. The technique is most useful for ab initio
      simulations.

PMID- 12513646
TI  - The establishment of ECVAM and its progress since 1993.
AB  - The background to the establishment of ECVAM in 1991 is summarised, and progress
      made since 1993 is briefly reviewed in relation to 12 recommendations made at the
      ECVAM Opening Symposium in 1994 and to statements on tests for chemicals and
      biologicals endorsed by the ECVAM Scientific Advisory Committee since 1997.

PMID- 12513647
TI  - The principles of validation and the ECVAM validation process.
AB  - The validation of a test method is the process by which the relevance and
      reliability of the method are assessed for a particular purpose. It is an
      essential stage in the evolution of the method from its development to its
      acceptance and application for regulatory purposes. The principles according to
      which alternative tests should be validated have been agreed at an international
      level, although the actual process by which the validation process is conducted
      varies between different validation authorities. This paper summarises the
      principles of alternative test development and validation, and describes how the
      principles have been applied to the validation of in vitro tests by ECVAM.

PMID- 12513648
TI  - The Interagency Coordinating Committee on the Validation of Alternative Methods
      (ICCVAM): a review of the ICCVAM test method evaluation process and current
      international collaborations with the European Centre for the Validation of
      Alternative Methods (ECVAM).
AB  - Over the last decade, national authorities in the USA and Europe have launched
      initiatives to validate new and improved toxicological test methods. In the USA,
      the Interagency Coordinating Committee on the Validation of Alternative Methods
      (ICCVAM) and its supporting National Toxicology Program Interagency Center for
      the Evaluation of Alternative Toxicological Methods (NICEATM) were established by
      the Federal Government to work with test developers and Federal agencies to
      facilitate the validation, review, and adoption of new scientifically sound test
      methods, including alternatives that can refine, reduce, and replace animal use.
      In Europe, the European Centre for the Validation of Alternative Methods (ECVAM)
      was established to conduct validation studies on alternative test methods.
      Despite differences in organisational structure and processes, both organisations
      seek to achieve the adoption and use of alternative test methods. Accordingly,
      both have adopted similar validation and regulatory acceptance criteria.
      Collaborations and processes have also evolved to facilitate the international
      adoption of new test methods recommended by ECVAM and ICCVAM. These
      collaborations involve the sharing of expertise and data for test-method
      workshops and independent scientific peer reviews, and the adoption of processes
      to expedite the consideration of test methods already reviewed by the other
      organisation. More recently, NICEATM and ECVAM initiated a joint international
      validation study on in vitro methods for assessing acute systemic toxicity. These
      collaborations are expected to contribute to accelerated international adoption
      of harmonised new test methods that will support improved public health and
      provide for reduced and more-humane use of laboratory animals.

PMID- 12513649
TI  - Validation successes: chemicals.
AB  - The ECVAM validation concept, which was defined at two validation workshops held
      in Amden (Switzerland) in 1990 and 1994, and which takes into account the
      essential elements of prevalidation and biostatistically defined prediction
      models, has been officially accepted by European Union (EU) Member States and by
      the Federal regulatory agencies of the USA and the OECD. The ECVAM validation
      concept was introduced into the ongoing ECVAM/COLIPA validation study of in vitro
      phototoxicity tests, which ended successfully in 1998. The 3T3 neutral red uptake
      in vitro phototoxicity test was the first experimentally validated in vitro
      toxicity test recommended for regulatory purposes by the ECVAM Scientific
      Advisory Committee (ESAC). It was accepted by the EU into the legislation for
      chemicals in the year 2000. From 1996 to 1998, two in vitro skin corrosivity
      tests were successfully validated by ECVAM, and they were also officially
      accepted into the EU regulations for chemicals in the year 2000. Meanwhile, in
      2002, the OECD Test Guidelines Programme is considering the worldwide acceptance
      of the validated in vitro phototoxicity and corrosivity tests. Finally, from 1997
      to 2000, an ECVAM validation study on three in vitro embryotoxicity tests was
      successfully completed. Therefore, the three in vitro embryotoxicity tests, the
      whole embryo culture (WEC) test on rat embryos, the micromass (MM) test on limb
      bud cells of mouse embryos, and the embryonic stem cell test (EST) including a
      permanent embryonic mouse stem cell line, are considered for routine use in
      laboratories of the European pharmaceutical and chemicals industries.

PMID- 12513650
TI  - ECVAM's role in the implementation of the Three Rs concept in the field of
      biologicals.
AB  - Biologicals can be defined as products that are derived from living organisms or
      are produced by them. They include vaccines, hormones, monoclonal and polyclonal
      antibodies, blood products and rDNA products. The production of conventionally
      produced biologicals requires an extensive batch-related quality control, to
      ensure that these products are both safe and potent. As several of the control
      tests rely on animal models, it is inevitable that the large numbers of animals
      are used. Many initiatives have been undertaken in the last few decades to reduce
      and refine the use of animals in this area. ECVAM has been involved in many
      activities to support the development, validation and implementation of these
      Three Rs methods. The role that ECVAM has played in a number of validation
      studies is summarised. It is concluded that ECVAM should continue to support the
      activities that have been shown to be successful, preferably in collaboration
      with the regulatory bodies.

PMID- 12513651
TI  - Comparison and validation of novel pyrogen tests based on the human fever
      reaction.
AB  - The Limulus amoebocyte lysate (LAL) test has replaced about 80% of the use of the
      rabbit pyrogen test. Ideally, human-based in vitro tests are needed, to replace
      the remaining use of the rabbit test and the use of the LAL test. The progress of
      an EU-funded project is described, in which a number of in vitro tests, based on
      the human fever reaction are passing through a prevalidation study on the way to
      evaluation in a formal validation study.

PMID- 12513652
TI  - Transepithelial resistance and inulin permeability as endpoints in in vitro
      nephrotoxicity testing.
AB  - Transepithelial electrical resistance (RT) and the flux of fluorescein
      isothiocyanate (FITC) across Madin Darby canine kidney (MDCK) strain 1 cells and
      porcine epithelial kidney (LLC-PK1) monolayers were compared between three
      laboratories for a range of nephrotoxins. The precision of the REMS AutoSampler
      was similar to that of the Ussing chamber and the ENDOHM technique, but superior
      to using chopstick electrodes, for measurements of resistance. The nephrotoxins
      used were selective for the proximal tubule, and in all cases, LLC-PK1 cells were
      more sensitive than MDCK cells. In most cases, change in RT was a more sensitive
      indicator of damage than alterations in FITC flux. The REMS system provides high
      intra-plate precision for RT measurements and is a higher throughput system,
      which is applicable to screening for nephrotoxicity in vitro.

PMID- 12513653
TI  - Ocular safety: a silent (in vitro) success story.
AB  - Ocular irritation testing has been one of the animal test methods most criticised
      by animal welfare advocates. Additional criticism has arisen from within the
      scientific community, based on the variability of the animal test results and the
      questionable relevance of the extremely high dose levels employed. As a result,
      the Draize eye irritation test has been one of the main targets for in vitro
      replacement. Despite extensive efforts, however, there is still no in vitro
      method that is fully validated as a regulatory replacement. In spite of this,
      many individual companies are using diverse in vitro ocular irritation tests to
      gain important safety and efficacy information about their products and raw
      materials, eliminating the need for animal testing in the process. This is done
      in a safe fashion by applying intelligent testing paradigms. ECVAM has played a
      major role in this success, through its many programmes that have emphasised the
      importance of understanding the true toxicological need, and then using in vitro
      tests to provide that information. Thus, even in the absence of a successfully
      validated regulatory assay, the desired result of reducing animal testing is
      being met.

PMID- 12513654
TI  - In vitro tests for haematotoxicity: prediction of drug-induced myelosuppression
      by the CFU-GM assay.
AB  - In a prevalidation study, a standard operating procedure (SOP) for human and
      mouse in vitro tests was developed, for evaluating the potential haematotoxicity
      of xenobiotics in terms of their direct, adverse effects on the myeloid colony
      forming unit (CFU-GM). Based on the adjustment of the mouse-derived maximum
      tolerated dose (MTD), a prediction model was set up to calculate the human MTD,
      and an international blind trial was designed to apply this model to the clinical
      neutropenia of 23 drugs including 17 antineoplastics. The model correctly
      predicted the human MTD for 20 drugs out of the 23 (87%). This high percentage of
      predictivity, and the reproducibility of the SOP testing, confirmed the
      scientific validation of this model, and suggest promising applications for
      developing and validating other in vitro methods for use in haematotoxicology.

PMID- 12513655
TI  - The current status and future applicability of quantitative structure-activity
      relationships (QSARs) in predicting toxicity.
AB  - The current status of quantitative structure-activity relationships (QSARs) in
      predicting toxicity is assessed. Widespread use of these methods to predict
      toxicity from chemical structure is possible, both by industry to develop new
      compounds, and also by regulatory agencies. The current use of QSARs is
      restricted by the lack of suitable toxicity data available for modelling, the
      suitability of simplistic modelling approaches for the prediction of certain
      endpoints, and the poor definition and utilisation of the applicability domain of
      models. Suggestions to resolve these issues are made.

PMID- 12513656
TI  - The necessity of biokinetic information in the interpretation of in vitro
      toxicity data.
AB  - Data derived from in vitro toxicity studies are not directly applicable in an
      assessment of the toxicity of compounds in intact organisms. The major limitation
      is the lack of knowledge of biokinetic behaviour in vivo. Since the toxicity of a
      compound will be determined by the critical concentration (or other dose metric)
      of the critical compound (or a metabolite thereof) at the critical site of toxic
      action, biokinetic behaviour must be taken into account. Possibilities of
      biokinetic modelling on the basis of in vitro and other non-animal data are
      discussed, and the application of the results in hazard and risk-assessment
      schedules is considered.

PMID- 12513657
TI  - Selected biostatistical aspects of the validation of in vitro toxicological
      assays.
AB  - An overview is presented on selected biostatistical aspects of the validation of
      in vitro toxicological assays. Primarily, the statistical analysis of single
      assays is discussed. Several approaches are compared for the possible non
      monotonic dose-response relationship with a priori unknown shapes. The use of
      confidence intervals instead of p values for toxicologically appropriate decision
      making is explained. New methods are discussed for demonstrating interlaboratory
      similarity for dose-response designs are discussed. For validation, the
      inappropriateness of the concordance coefficient is shown, and sensitive and
      specificity as well as predictive values are proposed as alternatives. The
      problem of the missing gold standard is highlighted.

PMID- 12513658
TI  - Barriers, nephrotoxicology and chronic testing in vitro.
AB  - In many organs of the human body, there are effective physiological barriers
      which contribute to regulation of the uptake, transport and secretion of
      endogenous and exogenous materials. ECVAM is involved in the development of
      several in vitro models for detecting damage to various barriers, for example,
      the renal epithelium, the intestinal barrier, and the blood-brain barrier, after
      acute and chronic exposure to chemicals and products of various kinds. Long-term
      toxicity testing is an important issue in toxicology. At present, there are no
      generally accepted in vitro models available for replacing chronic testing in
      animals. Under chronic exposure conditions, the cellular response is larger than
      that which can be predicted in the standard cytotoxicity models. Therefore, the
      approach to predicting chronic toxicity will need to involve more-complex in
      vitro models. Several in vitro long-term toxicity systems currently available are
      under evaluation.

PMID- 12513659
TI  - Development of a testing strategy for detecting embryotoxic hazards of chemicals
      in vitro by using embryonic stem cell models.
AB  - The importance of developing in vitro tests for embryotoxicity is discussed, and
      ECVAM's work with its collaborators is summarised. Studies are in progress to
      find new endpoints for use in the scientifically validated embryonic stem (ES)
      cell test, so that the potential for chemical effects on endodermal, mesodermal
      and/or ectodermal differentiation can be identified. This involves, inter alia,
      the use of genetically modified ES cells.

PMID- 12513660
TI  - Haematotoxicology: scientific basis and regulatory aspects.
AB  - Haematopoietic tissues are the targets of numerous xenobiotics. The purpose of in
      vitro haematotoxicology is the prediction of adverse haematological effects from
      toxicants on human haematopoietic targets under controlled experimental
      conditions in the laboratory. Building on its foundations in experimental
      haematology and the wealth of haematotoxicological data found in experimental
      oncology, this field of alternative toxicology has developed rapidly during the
      past decade. Preclinical and clinical drug development for anti-cancer drugs
      differs from that for other pharmaceuticals, because of the life-threatening
      nature of the disease. Treatment with anti-cancer drugs at clinically efficacious
      doses usually induces serious side-effects. The design of preclinical toxicology
      studies for anti-cancer drugs is intended to identify a safe clinical starting
      dose, characterise toxicities that could be encountered in human clinical trials,
      and determine whether these toxicities are reversible, manageable, and
      predictable. Although the myeloid colony-forming unit (CFU-GM) progenitor is most
      frequently evaluated, other defined progenitors and stem cells, as well as cell
      types found in the marrow stroma, can now be evaluated in vitro. Genetic damage
      to haematopoietic cells can occur in the absence of any overt haematological
      signs. The development of tissue-specific screening systems that are able to give
      information about the toxic effects of chemicals, drugs and environmental hazards
      on target genes is needed, in order to make preliminary decisions or to set
      priorities for selection among large groups of chemicals and possible drugs.

PMID- 12513661
TI  - Metabolism-mediated neurotoxicity: the significance of genetically engineered
      cell lines and new three-dimensional cell cultures.
AB  - Until now, no in vitro methods for determining neurotoxic effects, on Phase I and
      Phase II biotransformation-driven metabolite formation or for the evaluation of
      the metabolism-mediated hazard of a chemical, have been validated. The current
      test guidelines are based on studies in vivo, involving animals exposed to the
      test substance. Novel in vitro testing instead of animal testing is required by
      Directive 86/609/EEC. In the EU White Paper on a Strategy for a Future Chemicals
      Policy, which may result in up to 20,000 chemicals being screened for toxicity,
      the use of non-animal test methods is seen as essential and is encouraged. The
      aim of the present work was to demonstrate the significance of novel
      technologies, including the use of genetically engineered cell lines and three
      dimensional cell culture techniques for direct application in the regulatory
      hazard-assessment process. Furthermore, attempts were made to make in vitro
      toxicity tests for specific applications more-readily available for inclusion in
      the chemical hazard-assessment process, by exploiting advances made in the life
      sciences.

PMID- 12513662
TI  - ECVAM's research and validation activities in the fields of topical toxicity and
      human studies.
AB  - This paper outlines the research, prevalidation and validation activities that
      ECVAM has undertaken in collaboration with its partners in the field of topical
      toxicity testing and human volunteer studies, from its creation until now (1994
      2002).

PMID- 12513663
TI  - ECVAM's activities on biologicals.
AB  - This paper summarises key activities initiated and the progress achieved between
      April 1993 and June 2002 in implementing the Three Rs in one of ECVAM's priority
      areas - the production and quality control of biologicals. These have included:
      organising nine key workshops; financially supporting and/or participating in a
      number of prevalidation and/or validation studies; financial contributions and
      sponsorship to relevant international workshops, symposia and conferences; and
      financial support for the compilation of manuals and expert reports, and training
      in test methods. The paper complements the papers of Hendriksen et al. and
      Cussler et al. included in these proceedings.

PMID- 12513664
TI  - Genomics: an in vitro toxicology point of view.
AB  - Genomics, and in particular its derived discipline, toxicogenomics, are rapidly
      developing technologies, which permit studies on the impact of chemicals and
      drugs on gene expression in particular biological systems. Enormous amounts of
      data will be provided in the context of mechanistic and predictive toxicology
      from the use of the DNA microarray approach for the simultaneous analysis of the
      expression pattern of multiple genes. The high-throughput requirement of these
      approaches necessitate in vitro cell culture systems. This article will give a
      short overview of the areas of ECVAM's research in which this technology will
      initially be applied.

PMID- 12513665
TI  - ECVAM's activities on computer modelling and integrated testing.
AB  - This paper introduces the basic concepts of quantitative structure-activity
      relationship (QSAR), expert system and integrated testing strategy, and explains
      how the analogy between QSARs and prediction models leads naturally to criteria
      for the validation of QSARs. ECVAM's in-house research programme on QSAR
      modelling and integrated testing is summarised, along with plans for the
      validation of QSAR models and expert system rulebases at the European Union
      level.

PMID- 12513666
TI  - The ECVAM Scientific Information Service (SIS).
AB  - The aim of this ECVAM Status Seminar was to critically review the contributions
      made by ECVAM in relation to its four main task. The establishment and
      maintenance of the ECVAM Scientific Information Service (SIS) is a precise means
      of fulfilling one of these four principal duties of ECVAM. The major achievements
      of the SIS, and the efforts required to achieve them, are discussed, together
      with the immediate future for the SIS.

PMID- 12513667
TI  - Information: needs for the future.
AB  - The four central questions surrounding the use of information are: where to find
      it; how to find it; how to present it; and how to maintain information
      availability and information literacy. It is usually assumed that the main source
      of information for most scientists is the peer-reviewed journal literature.
      Traditional journal publishing is beset with a number of problems. Although
      electronic publishing might possibly solve some of these, it in turn introduces
      new problems. Further problems arise with respect to secondary sources which, in
      some cases, are being supplemented by electronic archives of full-text documents.
      One fundamental question that arises when considering any large collection of
      documents or of records about documents is whether or not to index them, and how
      to index them. The pros and cons of free-text searching versus the use of
      controlled vocabularies are discussed, as is the importance of harmonising the
      Three Rs-related terminology of existing and proposed thesauri. However, there is
      a further problem that documents pertinent to the Three Rs are not always indexed
      from this point of view. Authors need to be made aware that, if the information
      is not provided in the abstract, there is no easy way to identify and retrieve
      this document from a database. Small specialised databases on the Three Rs in
      relation to specific subject areas could provide a further solution, especially
      if they provide references to conference proceedings and book chapters, which are
      not usually found in the large bibliographical databases. The provision of
      training in the use of information resources, and the establishment and
      maintenance of these resources require investment of money and professional
      skills. Finally, the future of Three Rs information depends on a recognition that
      this in an important topic which deserves more than lip service.

PMID- 12513668
TI  - The ECVAM workshops: a critical assessment of their impact on the development,
      validation and acceptance of alternative methods.
AB  - ECVAM initiated its workshop programme in 1994, to enable it to become well
      informed about the state of the art of non-animal test development and
      validation, and about the possible incorporation of alternatives into regulatory
      requirements for safety testing. Fifty-one such workshops have been held on
      specific topics, up to 2002. In these workshops, the current status of in vitro
      tests and their potential uses were reviewed and recommendations were made as to
      the best ways forward to progress and enhance the utilisation of in vitro
      methods. Reports for 46 of these workshops have been published in ATLA. Most of
      the workshops focused on in vitro replacement methods, although an increasing
      number have dealt with reduction and refinement. The recommendations in the ECVAM
      workshops have been progressed further by: a) the formation of ECVAM task forces;
      b) the organisation of further workshops; c) the activities of scientific
      committees; d) the provision of earmarked research funding; and e) the conduct of
      validation studies. Examples of each of these activities are discussed. Some
      individual workshops are covered in more detail and several recommendations that
      have so far not been acted on are also considered. The workshops and their
      reports have had a substantial effect on the development and implementation of
      alternative methods, and have been a major factor in contributing to the success
      of the first nine years of ECVAM's existence. It is strongly recommended that
      ECVAM continues to organise workshops and to publish their findings, and several
      suggestions are made for topics of future workshops.

PMID- 12513669
TI  - ECVAM: desperately needed or superfluous? An animal welfare perspective.
AB  - Eurogroup for Animal Welfare is the umbrella organisation of the major animal
      welfare organisations in Europe. Whereas its long-term goal is the complete
      replacement of animal experiments by methods that do not involve pain, suffering
      or distress in animals, it is also committed to any reasonable effort to reduce
      and refine animal experiments, as long as these continue to be carried out.
      Eurogroup therefore supports the activities of ECVAM, and it acknowledges the
      contributions to animal protection in various areas of animal use for scientific
      purposes made by ECVAM to date. Eurogroup is not satisfied with the number of
      alternative methods accepted in the past, but it sees the main responsibility for
      the slow progress as being outside ECVAM. The insufficient involvement of ECVAM
      by the EU Commission in various issues that would require its competence is also
      a matter of concern to Eurogroup.

PMID- 12513670
TI  - ECVAM's collaborations with academia.
AB  - The encouragement of ECVAM's connections with academia through direct
      collaboration and co-sponsored studentships has resulted in the successful
      achievement of higher degree qualifications for the young participants, and the
      development and promotion of alternative methods. So far, 26 students have been
      registered for higher degrees, of which 13 have been awarded so far, and 16
      university departments in nine European countries have been directly involved.
      When other collaborations are included, the number of ECVAM's interactions with
      academic institutions rises to 33 departments in eleven countries, including the
      USA. In addition, through contracts awarded to academic institutions and other
      forms of collaboration, the prevalidation and validation of alternative methods
      have been progressed.

PMID- 12513671
TI  - ECVAM, ECETOC and the EU chemicals policy.
AB  - ECVAM's initiatives in validation have received significant support from the
      European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC),
      especially through the provision of reference chemical data banks, which contain
      peer-reviewed, high-quality in vivo data on commercially available chemical
      substances. Chemicals have been selected from these ECETOC data banks for
      validation studies on alternative methods for skin corrosion and irritation and
      for eye irritation and, in addition, an ECETOC task force peer-reviewed the
      selection and classification, on the basis of in vivo data, of chemicals used in
      the validation of three alternative methods for developmental toxicity. More
      recently, ECVAM and ECETOC have been pursuing parallel initiatives on the
      proposed new EU chemicals policy, with the common goals of ensuring that industry
      and European Commission resources are used to investigate only those chemicals
      that pose a significant risk to human health and the environment, and that the
      Policy requires that any testing which is required follows the Three Rs
      principles of reduction, refinement and replacement.

PMID- 12513672
TI  - The contributions of the European cosmetics industry to the development of
      alternatives to animal testing: dialogue with ECVAM and future challenges.
AB  - COLIPA (the European Federation of the Cosmetics Industry) represents 24
      international companies and 2000 small and medium-sized enterprises. Together
      with ECVAM, COLIPA has been involved in the development and validation of
      alternative methods since the beginning of the validation efforts. The work of
      the Steering Committee on Alternatives to Animal Testing (SCAAT) is based on
      collaboration between companies, but also with academia, trade associations, the
      Scientific Committee on Cosmetics and Non-Food Products (SCCNFP), European
      Commission Directorates General, and ECVAM. Some success has been achieved, but
      some validation efforts have failed. One lesson is that the search for
      alternatives requires a lot of humility.

PMID- 12513673
TI  - Dialogue and collaboration with ECVAM: the view of the EFPIA.
AB  - An evaluation is presented of past experience of dialogue and collaboration of
      ECVAM with the European Federation of Pharmaceutical Industries and Associations
      (EFPIA) over the last nine years. Lessons learnt from the viewpoint of EFPIA
      company representatives are given. Also, proposals for the future ECVAM approach
      are made, such as support for other research areas for new methods to be
      validated, giving realistic statements to ECVAM's EU and external customers, and
      being open to any new technology development that might help in opening and
      establishing new alternative avenues. Finally, the need for proper publications
      on the implementation of alternatives is recommended, for example, through the
      existing national platforms and their umbrella organisation, ecopa.

PMID- 12513674
TI  - ecopa: a powerful concept in the way forward for alternative methods.
AB  - ecopa, the European Consensus-Platform on Alternatives, is an international not
      for-profit organisation, based in Belgium and complying with Belgium Law. It is
      the only quadripartite organisation that promotes the Three Rs at the European
      level. Ecopa brings together national consensus platforms on alternative methods.
      Consensus means that all parties concerned are represented, including animal
      welfare, industry, academia and government. Ecopa currently includes the National
      Platforms of 14 EU Member State (or future Member State; eight full members,
      namely, Austria, Belgium, Finland, Germany, The Netherlands, Spain, Switzerland
      and the UK, and six associate members, being the Czech Republic, Denmark, Italy,
      Norway, Poland and Sweden). Ecopa also has three working groups, concerned with:
      a) the 6th Framework Programme of the EC for Research, Technological Development
      and Demonstration Activities; b) the EC White Paper Strategy for a Future EU
      Chemicals Policy; and c) the formation of educational programmes on alternative
      methods within the EU. Ecopa is thus uniquely placed and has huge expertise to
      offer to the debate around political topics, including the White Paper, the 6th
      Framework Programme, and the 7th Amendment of the EU Cosmetics Directive. Ecopa
      should be considered a key stakeholder by the European Commission and Parliament,
      and it is essential that the views of ecopa are fully incorporated into future
      legislation. Recently, the ecopa working groups made a strong common statement on
      the Chemicals Policy White Paper and made a number of recommendations to the
      Commission based on scientific, practical and realistic grounds. These are to be
      found on the ecopa Web site (http://www.ecopa.tsx.org/).

PMID- 12513675
TI  - ECVAM'S activities in the EU candidate countries.
AB  - ECVAM has been given a special grant for collaborative projects on
      alternative/advanced testing methods involving eleven Candidate Countries for
      membership of the European Union (Bulgaria, Cyprus, the Czech Republic, Estonia,
      Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia). The project
      involves the promotion of the Three Rs (reduction, refinement, replacement)
      concept of Russell & Burch, in cooperation with appropriate individuals and
      national and international organisations in the Candidate Countries themselves,
      and elsewhere. The scope of the programme's activities covers: conferences in
      some of the Candidate Countries, workshops, training courses, training visits,
      and technology development/transfer initiatives. A database of contacts in the
      Candidate Countries and in relevant institutions in other countries, is being
      compiled.

PMID- 12513676
TI  - Dialogue and collaboration: a personal view on laboratory animal welfare
      developments in general, and on ECVAM's first decade in particular.
AB  - A personal view is presented on progress made during the last 25 years in
      applying the Three Rs (reduction, refinement, replacement) to animal testing in
      regulatory toxicology, with an emphasis on "good moments" (for example,
      international workshops on the principles and practical application of the
      validation process and on regulatory acceptance) and "not-so-good moments" (for
      example, the time taken to accept alternatives to the LD50 test and to accept in
      vitro tests for skin absorption as OECD Test Guidelines). The importance of
      dialogue and cooperation between international coordinating centres and
      scientific activities at the national level is stressed, as exemplified by the
      work of ECVAM during its first decade.

PMID- 12513677
TI  - The EC White Paper on a Strategy for a Future Chemicals Policy.
AB  - The European Commission (EC) White Paper on a Strategy for a Future Chemicals
      Policy calls for the collection of adequate information about chemicals, in order
      to ensure their appropriate risk management. The White Paper proposes a stepwise
      and flexible approach to all chemicals produced in amounts above 1
      tonne/year/manufacturer, including testing, if information cannot be provided by
      other means. The required information should be collected by the end of 2012. The
      EC services are currently preparing the drafts for the future chemicals
      legislation.

PMID- 12513678
TI  - The seventh amendment to the cosmetics directive: what does DG enterprise want
      from ECVAM?
AB  - A short overview is given of the current situation regarding the draft seventh
      amendment to the EU cosmetics directive, Directive 76/768/EEC. Future
      perspectives are discussed.

PMID- 12513679
TI  - Directive 86/609/EEC on the protection of animals used for experimental and other
      scientific purposes.
AB  - Directive 86/609/EEC regulates the use of animals for experimental and other
      scientific purposes in the EU. The Directive seeks to improve the controls on the
      use of laboratory animals, and to set minimum standards for housing and care, and
      for the training of personnel handling these animals and supervising the
      experiments. It also aims to reduce the numbers of animals used for experiments,
      by encouraging the development and the validation of alternative methods to
      replace animals methods. Since the scientific basis of the Directive dates back
      at least 15 years, the Commission is planning on an in-depth revision of the
      Directive. The Commission aims to have a first draft proposal ready by the end of
      2003.

PMID- 12513680
TI  - ECVAM and pharmaceuticals.
AB  - In the pharmaceutical industry, toxicology testing is normally done by
      preclinical scientists during the Development phase. In the last decade, the
      implementation of high-throughput screens during the Discovery phase has resulted
      in an ever-increasing number of lead candidates to be selected for drug
      development. The low throughput of the conventional safety tests is a bottleneck
      in the drug-development process. The pharmaceutical industry needs new
      techniques, down-scaled tests and in vitro alternative test models to determine
      the absorption, distribution, metabolism, and excretion (ADME) and toxicology
      profiles of compounds in the late-Discovery phase and/or early in the Development
      phase. Medium-throughput ADME and toxicity tests will enhance the selection of
      safer new chemical entities for animals and/or humans. Consequently, this testing
      strategy will not only reduce the use of resources and the overall development
      time, but will also result in a substantial decrease in animal use.

PMID- 12513681
TI  - Future activities: ECVAM and the quality control of biologicals.
AB  - ECVAM's activities in the field of biologicals have contributed in many ways to
      the successful incorporation of Three Rs methods, as summarised elsewhere in
      these proceedings. The progress achieved is impressive, but large numbers of
      animals are still needed in order to meet the requirements stipulated by various
      regulations. ECVAM's activities in this area should therefore be continued and
      extended. Besides the well-established organisation of ECVAM workshops and
      contributions to conferences, further prevalidation and validation studies should
      be funded. In addition, studies on refinement, and training courses on validated
      and well-established Three Rs methods, could be initiated. There is a need for
      more communication and information exchange, especially between regulators and
      industry concerning the Three Rs. ECVAM could provide a suitable forum for such
      activities. An ECVAM Biologicals Task Force should be established in order to
      define a list of priorities.

PMID- 12513682
TI  - ECVAM-ICCVAM: prospects for future collaboration.
AB  - The level and complexity of testing for hazard and risk assessment of marketed
      products and environmental agents has increased substantially over time,
      resulting in the use of greater numbers of both animals and humans for testing.
      Today, industry and regulatory bodies worldwide face increasing pressures to
      demonstrate responsible utilisation of laboratory animals, to limit their use,
      and to employ alternative non-animal tests. Institutions have also been
      established to identify, encourage development of, conduct research on, and
      validate new, improved, and surrogate test methods that will reduce and replace
      animal use. Two such organisations are ECVAM and the Interagency Coordinating
      Committee for the Validation of Alternative Methods (ICCVAM). As the evolutionary
      changes occurring in the field of toxicology result in an unprecedented increase
      in the introduction of alternative methodologies, these will strain the
      capacities of such alternative methods institutions. That realisation is causing
      a shift in thinking and creating an impetus to seek approaches by which to
      collaborate and develop more-efficient operational procedures for the validation
      and regulatory acceptance of alternative methods. Similarities in objectives,
      functions, scientific standards, and commitment to the principles of validation
      and animal welfare support the value of a cooperative arrangement between ECVAM
      and ICCVAM, to minimise duplication of effort, maximise productivity, and
      influence the international adoption of alternative tests. Opportunities for
      ECVAM-ICCVAM collaboration are discussed, which illustrate the feasibility and
      potential benefits of such a partnership.

PMID- 12513683
TI  - The future of ECVAM: a personal perspective.
AB  - Progress made in the practical application of the validation process is
      summarised, and some of the remaining problems are considered. Highlights of the
      first ten years of ECVAM are reviewed, andECVAM's activities as a route of
      communication on the Three Rs are discussed. Finally, some suggestions are made
      for maintaining ECVAM's momentum in the future, especially in relation to the
      challenge and opportunity for alternative methods afforded by the new EU
      Chemicals Policy.

PMID- 12513684
TI  - Evaluation and prevalidation of an immunotoxicity test based on human whole-blood
      cytokine release.
AB  - Immunotoxicology is a relatively new field in toxicology, and is one of emerging
      importance, because immunotoxicity appears to contribute to the development of
      cancer, autoimmune disorders, allergies and other diseases. At present, there is
      a lack of human cell-based immunotoxicity assays for predicting the toxicity of
      xenobiotics toward the immune system in a simple, fast, economical and reliable
      way. Existing immunotoxicity tests are mainly performed in animals, although
      species differences favour human-based testing. Whole-blood cytokine release
      models have attracted increasing interest, and are broadly used for
      pharmacological in vitro and ex vivo studies, as well as for pyrogenicity
      testing. We have adapted those methods for immunotoxicity testing, to permit the
      potency testing of immunostimulants and immunosuppressants. Following stimulation
      with a lipopolysaccharide or staphylococcal enterotoxin B, monocytes and
      lymphocytes release interleukin-1beta and interleukin-4, respectively. Thirty-one
      pharmaceutical compounds, with known effects on the immune system, were used to
      optimise and standardise the method, by analysing their effects on cytokine
      release. The in vitro results were expressed as IC50 values for
      immunosuppression, and SC(4) (fourfold increase) values for immunostimulation,
      and compared with therapeutic serum concentrations of the compounds in patients,
      and in vivo LD50 values from animal studies. The in vitro results correlated well
      with the in vivo data, so the test appears to reflect immunomodulation. Results
      were reproducible (CV = 20 +/- 5%), and the method could be transferred to
      another laboratory (r(2) = 0.99). We therefore propose this method for further
      validation and for use in immunotoxicity testing strategies.

PMID- 12513685
TI  - Arsenic toxicity and HSP70 expression in Xenopus laevis embryos.
AB  - The evaluation of the effect of trace metals on health can be difficult, because
      of their presence in the environment in various chemical forms. Exposure to
      arsenic compounds is an example of this complexity, as it can be present in the
      environment in inorganic and organic forms. The effects of arsenic in vertebrates
      are complicated by several variables, such as speciation of the element, the
      exposure route, and the susceptibility of the particular animal species. The
      embryotoxicity and teratogenicity of three arsenic species - sodium arsenite
      (NaAsO(2)), disodium hydrogen arsenate (Na(2)HAsO(4)) and dimethylarsinic acid
      [(CH3)2AsOOH] - were evaluated by the modified frog embryo teratogenic assay on
      Xenopus (FETAX). We also show how the classical FETAX endpoints, based on
      morphological and morphometrical analysis, can conveniently be integrated with
      the study of molecular markers. Possible changes in the expression of the mRNA
      for the heat-shock protein HSP70, following exposure to NaAsO(2), were examined
      by using the reverse transcriptase polymerase chain reaction. HSP70 mRNA is
      strongly induced by arsenic.

PMID- 12513686
TI  - Chronic activation of extracellular-signal-regulated protein kinases by
      phenylephrine is required to elicit a hypertrophic response in cardiac myocytes.
AB  - Extracellular-signal-regulated protein kinases (ERKs) are activated rapidly and
      transiently in response to phenylephrine (PE) and endothelin-1 (ET-1) in cardiac
      myocytes, but whether this is linked to the subsequent development of the
      hypertrophic phenotype remains equivocal. To investigate this, we examined the
      dependence of the hypertrophic response on the length of exposure to PE in
      neonatal myocyte cultures. In addition to the initial transient activation of
      ERKs (maximum at 5-10 min), PE (10 microM) induced a second, more prolonged peak
      of activity several hours later. The activity of a transfected atrial natriuretic
      factor-luciferase reporter gene was increased 10- to 24-fold by PE. This response
      was inhibited by the alpha(1)-antagonist prazosin (100 nM) and by U0126 (10
      microM) and PD184352 (1 microM), inhibitors of ERK activation, irrespective of
      whether these were added before or up to 24 h after the addition of PE. Prazosin
      had no effect on ET-1 (50 nM)-stimulated atrial natriuretic factor-luciferase
      activity. Protein synthesis was enhanced by 35+/-6% by PE, and this was blocked
      by prazosin added 1 h after the addition of PE, but decreased only by half when
      added 8 h after PE. Similarly, PE (48 h) increased myocyte area by 49% and this
      was prevented by prazosin added 1 h after PE, but decreased only by half when
      added at 24 h. These results demonstrate that prolonged exposure to PE is
      required to elicit alterations in gene expression, protein synthesis and cell
      size, characteristic of hypertrophied myocytes, and they confirm that the initial
      peak of ERK activity is insufficient to trigger hypertrophic responses.

PMID- 12513687
TI  - Discrimination of intracellular calcium store subcompartments using TRPV1
      (transient receptor potential channel, vanilloid subfamily member 1) release
      channel activity.
AB  - The store-operated calcium-release-activated calcium current, I (CRAC), is a
      major mechanism for calcium entry into non-excitable cells. I (CRAC) refills
      calcium stores and permits sustained calcium signalling. The relationship between
      inositol 1,4,5-trisphosphate receptor (InsP(3)R)-containing stores and I (CRAC)
      is not understood. A model of global InsP(3)R store depletion coupling with I
      (CRAC) activation may be simplistic, since intracellular stores are heterogeneous
      in their release and refilling activities. Here we use a ligand-gated calcium
      channel, TRPV1 (transient receptor potential channel, vanilloid subfamily member
      1), as a new tool to probe store heterogeneity and define intracellular calcium
      compartments in a mast cell line. TRPV1 has activity as an intracellular release
      channel but does not mediate global calcium store depletion and does not invade a
      store coupled with I (CRAC). Intracellular TRPV1 localizes to a subset of the
      InsP(3)R-containing stores. TRPV1 sensitivity functionally subdivides the InsP(3)
      sensitive store, as does heterogeneity in the sarcoplasmic/endoplasmic-reticulum
      Ca(2+)-ATPase isoforms responsible for store refilling. These results provide
      unequivocal evidence that a specific 'CRAC store' exists within the InsP(3)
      releasable calcium stores and describe a novel methodology for manipulation of
      intracellular free calcium.

PMID- 12513688
TI  - Human mismatch-repair protein MutL homologue 1 (MLH1) interacts with Escherichia
      coli MutL and MutS in vivo and in vitro: a simple genetic system to assay MLH1
      function.
AB  - A simple genetic system has been developed to test the effect of over-expression
      of wild-type or mutated human MutL homologue 1 (hMLH1) proteins on methyl
      directed mismatch repair (MMR) in Escherichia coli. The system relies on
      detection of Lac(+) revertants using MMR-proficient or MMR-deficient E. coli
      strains carrying a lac +1 frameshift mutation expressing hMLH1 proteins. We
      report that expression of wild-type hMLH1 protein causes an approx. 19-fold
      increase in mutation rates. The mutator phenotype was due to the ability of hMLH1
      protein to interact with bacterial MutL and MutS proteins, thereby interfering
      with the formation of complexes between MMR proteins and mismatched DNA.
      Conversely, expression of proteins encoded by alleles deriving from hereditary
      non-polyposis-colon-cancer (HNPCC) families decreases mutation rates, depending
      on the specific amino acid substitutions. These effects parallel the MutL-and
      MutS-binding and ATP-binding/hydrolysis activities of the mutated proteins.

PMID- 12513689
TI  - Transcriptional regulation of the human Sp1 gene promoter by the specificity
      protein (Sp) family members nuclear factor Y (NF-Y) and E2F.
AB  - We analysed in detail the minimal promoter of transcription factor Sp1, which
      extends 217 bp from the initiation of transcription. Within this sequence we
      identified putative binding sites for Sp1, nuclear factor Y (NF-Y), activator
      protein 2 ('AP-2'), CCAAT/enhancer-binding protein ('C/EBP') and E2F
      transcription factors. In one case, the boxes for Sp1 and NF-Y are overlapping.
      Gel-shift and supershift assays demonstrated specific binding of Sp1, Sp3 and NF
      Y proteins. Transient transfections and luciferase assays revealed activation of
      the Sp1 minimal promoter upon overexpression of Sp1 itself, NF-Y and E2F. Whereas
      overexpression of NF-Y or E2F had an additive effect on Sp1 overexpression, the
      activation of Sp1 transcription due to Sp1 was counteracted by Sp3
      overexpression. Mutagenesis analysis of the NFY/Sp1-overlapping box revealed that
      both factors compete for this box, and that when the NF-Y site of this
      overlapping box is specifically mutated there is an increase in Sp1 binding, thus
      increasing transcriptional activity. These results help to explain the complex
      regulation of the Sp1 gene, which depends on the relative amounts of Sp1, Sp3,
      E2F and NF-Y proteins in the cell.

PMID- 12513690
TI  - Kinetic studies of rat liver hexokinase D ('glucokinase') in non-co-operative
      conditions show an ordered mechanism with MgADP as the last product to be
      released.
AB  - The kinetic mechanism of rat liver hexokinase D ('glucokinase') was studied under
      non-co-operative conditions with 2-deoxyglucose as substrate, chosen to avoid
      uncertainties derived from the co-operativity observed with the physiological
      substrate, glucose. The enzyme shows hyperbolic kinetics with respect to both 2
      deoxyglucose and MgATP(2-), and the reaction follows a ternary-complex mechanism
      with K (m)=19.2+/-2.3 mM for 2-deoxyglucose and 0.56+/-0.05 mM for MgATP(2-).
      Product inhibition by MgADP(-) was mixed with respect to MgATP(2-) and was
      largely competitive with respect to 2-deoxyglucose, suggesting an ordered
      mechanism with 2-deoxyglucose as first substrate and MgADP(-) as last product.
      Dead-end inhibition by N -acetylglucosamine, AMP and the inert complex CrATP [the
      complex of ATP with chromium in the 3+ oxidation state, i.e. Cr(III)-ATP],
      studied with respect to both substrates, also supports an ordered mechanism with
      2-deoxyglucose as first substrate. AMP appears to bind both to the free enzyme
      and to the E*dGlc complex. Experiments involving protection against inactivation
      by 5,5'-dithiobis-(2-nitrobenzoic acid) support the existence of the E*MgADP(-)
      and E*AMP complexes suggested by the kinetic studies. MgADP(-), AMP, 2
      deoxyglucose, glucose and mannose were strong protectors, supporting the
      existence of binary complexes with the enzyme. Glucose 6-phosphate failed to
      protect, even at concentrations as high as 100 mM, and MgATP(2-) protected only
      slightly (12%). The inactivation results support the postulated ordered mechanism
      with 2-deoxyglucose as first substrate and MgADP(-) as last product. In addition,
      the straight-line dependence observed when the reciprocal value of the
      inactivation constant was plotted against the sugar-ligand concentration supports
      the view that there is just one sugar-binding site in hexokinase D.

PMID- 12513691
TI  - Functional implications of genetic variation in non-coding DNA for disease
      susceptibility and gene regulation.
AB  - The role of host genetic variation in determining susceptibility to complex
      disease traits is the subject of much research effort, but it often remains
      unclear whether disease-associated genetic polymorphisms are themselves
      functionally relevant or acting only as markers within an extended haplotype.
      Experimental approaches to investigate the functional impact of polymorphisms in
      non-coding regulatory DNA sequences for gene expression are discussed, including
      the role of gel-shift assays, DNA footprinting and reporter gene analysis. The
      limitations of different experimental approaches are presented together with
      future prospects for in vivo analysis. The strategic application of these
      functional approaches is discussed and illustrated by analysis of the role of
      genetic variation in the tumour necrosis factor promoter region in determining
      susceptibility to severe malaria.

PMID- 12513692
TI  - A newly established in vitro culture using transgenic Drosophila reveals
      functional coupling between the phospholipase A2-generated fatty acid cascade and
      lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in
      insect immunity.
AB  - Innate immunity is the first line of defence against infectious micro-organisms,
      and the basic mechanisms of pathogen recognition and response activation are
      evolutionarily conserved. In mammals, the innate immune response in combination
      with antigen-specific recognition is required for the activation of adaptive
      immunity. Therefore, innate immunity is a pharmaceutical target for the
      development of immune regulators. Here, for the purpose of pharmaceutical
      screening, we established an in vitro culture based on the innate immune response
      of Drosophila. The in vitro system is capable of measuring lipopolysaccharide
      (LPS)-dependent activation of the immune deficiency (imd) pathway, which is
      similar to the tumour necrosis factor signalling pathway in mammals. Screening
      revealed that well-known inhibitors of phospholipase A(2) (PLA(2)), dexamethasone
      (Dex) and p-bromophenacyl bromide (BPB) inhibit LPS-dependent activation of the
      imd pathway. The inhibitory effects of Dex and BPB were suppressed by the
      addition of an excess of three (arachidonic acid, eicosapentaenoic acid and gamma
      linolenic acid) of the fatty acids so far tested. Arachidonic acid, however, did
      not activate the imd pathway when used as the sole agonist. These findings
      indicate that PLA(2) participates in LPS-dependent activation of the imd pathway
      via the generation of arachidonic acid and other mediators, but requires
      additional signalling from LPS stimulation. Moreover, PLA(2) was activated in
      response to bacterial infection in Sarcophaga. These results suggest a functional
      link between the PLA(2)-generated fatty acid cascade and the LPS-stimulated imd
      pathway in insect immunity.

PMID- 12513693
TI  - Identification and cloning of two isoforms of human high-temperature requirement
      factor A3 (HtrA3), characterization of its genomic structure and comparison of
      its tissue distribution with HtrA1 and HtrA2.
AB  - In the present study, we identified an additional member of the human high
      temperature requirement factor A (HtrA) protein family, called pregnancy-related
      serine protease or HtrA3, which was most highly expressed in the heart and
      placenta. We cloned the full-length sequences of two forms (long and short) of
      human HtrA3 mRNA, located the gene on chromosome 4p16.1, determined its genomic
      structure and revealed how the two mRNA variants are produced through alternative
      splicing. The alternative splicing was also verified by Northern blotting. Four
      distinct domains were found for the long form HtrA3 protein: (i) an
      insulin/insulin-like growth factor binding domain, (ii) a Kazal-type S protease
      inhibitor domain, (iii) a trypsin protease domain and (iv) a PDZ domain. The
      short form is identical to the long form except it lacks the PDZ domain.
      Comparison of all members of human HtrA proteins, including their isoforms,
      suggests that both isoforms of HtrA3 represent active serine proteases, that they
      may have different substrate specificities and that HtrA3 may have similar
      functions to HtrA1. All three HtrA family members showed very different mRNA
      expression patterns in 76 human tissues, indicating a specific function for each.
      Interestingly, both HtrA1 and HtrA3 are highly expressed in the placenta.
      Identification of the tissue-specific function of each HtrA family member is
      clearly of importance.

PMID- 12513694
TI  - Complement C1r and C1s genes are duplicated in the mouse: differential expression
      generates alternative isomorphs in the liver and in the male reproductive system.
AB  - C1r and C1s are the serine proteases that form the catalytic unit of the C1
      complex, the first component of complement. In the present study, we found that
      the genes encoding murine C1r and C1s are duplicated. One set of these genes,
      referred to as c1rA and c1sA, are primarily expressed in the liver and are
      therefore the homologues of the human C1r and C1s genes. The other two genes,
      termed c1rB and c1sB, are expressed exclusively in male reproductive tissues,
      specifically the coagulating gland and the prostate. The predicted C1rB and C1sB
      proteins share 96 and 93% amino acid identity with C1rA and C1sA respectively.
      Most of the substitutions are clustered in the serine protease domains,
      suggesting differences in catalytic efficiencies and/or substrate specificities
      or alternatively adaptation to different physiological environments. The high
      homology of C1rB and C1sB with C1rA and C1sA in the non-catalytic regions
      indicates that they are probably capable of assembling the C1 complex. The
      expression of alternative genes encoding isomorphs of activating components of
      complement in male reproductive tissues raises the possibility of new mechanisms
      of complement activation in the male genital tract or of novel functions for
      complement proteases in reproduction.

PMID- 12513695
TI  - 3-Aminopropanal, formed during cerebral ischaemia, is a potent lysosomotropic
      neurotoxin.
AB  - Cytotoxic polyamine-derived amino aldehydes, formed during cerebral ischaemia,
      damage adjacent tissue (the so-called 'penumbra') not subject to the initial
      ischaemic insult. One such product is 3-aminopropanal (3-AP), a potent cytotoxin
      that accumulates in ischaemic brain, although the precise mechanisms responsible
      for its formation are still unclear. More relevant to the present investigations,
      the mechanisms by which such a small aldehydic compound might be cytotoxic are
      also not known, but we hypothesized that 3-AP, having the structure of a weak
      lysosomotropic base, might concentrate within lysosomes, making these organelles
      a probable focus of initial toxicity. Indeed, 3-AP leads to lysosomal rupture of
      D384 glioma cells, a process which clearly precedes caspase activation and
      apoptotic cell death. Immunohistochemistry reveals that 3-AP concentrates in the
      lysosomal compartment and prevention of this accumulation by the lysosomotropic
      base ammonia, NH(3), protects against 3-AP cytotoxicity by increasing lysosomal
      pH. A thiol compound, N-(2-mercaptopropionyl)glycine, reacts with and neutralizes
      3-AP and significantly inhibits cytoxocity. Both amino and aldehyde functions of
      3-AP are necessary for toxicity: the amino group confers lysosomotropism and the
      aldehyde is important for additional, presently unknown, reactions. We conclude
      that 3-AP exerts its toxic effects by accumulating intralysosomally, causing
      rupture of these organelles and releasing lysosomal enzymes which initiate
      caspase activation and apoptosis (or necrosis if the lysosomal rupture is
      extensive). These results may have implications for the development of new
      therapeutics designed to lessen secondary damage arising from focal cerebral
      ischaemia.

PMID- 12513696
TI  - pKa measurements from nuclear magnetic resonance of tyrosine-150 in class C beta
      lactamase.
AB  - 13C-NMR spectroscopy was used to estimate the p K a values for the Tyr(150)
      (Y150) residue in wild-type and mutant class C beta-lactamases. The tyrosine
      residues of the wild-type and mutant lactamases were replaced with (13)C-labelled
      L-tyrosine ([ phenol -4-(13)C]tyrosine) in order to observe the tyrosine residues
      selectively. Spectra of the wild-type and K67C mutant (Lys(67)-->Cys) enzyme were
      compared with the Y150C mutant lactamase spectra to identify the signal
      originating from Tyr(150). Titration experiments showed that the chemical shift
      of the Tyr(150) resonance in the wild-type enzyme is almost invariant in a range
      of 0.1 p.p.m. up to pH 11 and showed that the p K (a) of this residue is well
      above 11 in the substrate-free form. According to solvent accessibility
      calculations on X-ray-derived structures, the phenolic oxygen of Tyr(150), which
      is near the amino groups of Lys(315) and Lys(67), appears to have low solvent
      accessibility. These results suggest that, in the native enzyme, Tyr(150) in
      class C beta-lactamase of Citrobacter freundii GN346 is protonated and that when
      Tyr(150) loses a proton, a proton from Lys(67) would replace it. Consequently,
      Tyr(150) would be protonated during the entire titration.

PMID- 12513697
TI  - Hypertension in the Parsi community of Bombay: a study on prevalence, awareness
      and compliance to treatment.
AB  - BACKGROUND: Uncontrolled hypertension (HT) is an established risk factor for the
      development of vascular diseases. Prevalence varies in different communities and
      no such study has been conducted in the Parsi community living in Bombay, India.
      The objectives of this study were to determine the prevalence, awareness,
      compliance to medication and control of HT in this community. METHOD: We used a 1
      in 4 random selection of subjects who were > or = 20 years of age. A
      questionnaire was administered and the blood pressure (BP) was measured by a
      doctor. HT was defined as diastolic blood pressure (DBP) > or = 90 mm Hg +/-
      systolic pressure (SBP) > or = 140 mm Hg. Isolated systolic hypertension (ISH)
      was defined as SBP > or = 160 mm Hg with DBP < 90 mm Hg. Subsequently, we
      reanalysed the data using current definition of ISH as SBP > or = 140 mm Hg with
      DBP < 90 mm Hg. RESULTS: 2879 subjects > or = 20 years of age were randomly
      selected of which 2415 (84%) participated in the study. The overall prevalence of
      HT in the community was 36.4%, of whom 48.5% were unaware of their hypertensive
      status. Of those aware of having HT, 36.4% were non-compliant with their anti
      hypertensive drugs and only 13.6% had optimally controlled HT. Prevalence of ISH
      using the present criteria was 19.5% and 73% of hypertensives > or = 60 years had
      ISH. CONCLUSION: This study shows that prevalence of HT in the Parsi community is
      high and nearly half are unaware of their hypertensive status. ISH is the
      dominant form of HT in the elderly. Compliance to treatment is poor and optimal
      BP control is achieved in only a small minority. The study highlights the need
      for regular screening coupled with educational programs to detect and optimally
      treat HT in the community.

PMID- 12513698
TI  - Activity of opioid ligands in cells expressing cloned mu opioid receptors.
AB  - BACKGROUND: The aim of the present study was to describe the activity of a set of
      opioid drugs, including partial agonists, in a cell system expressing only mu
      opioid receptors. Receptor activation was assessed by measuring the inhibition of
      forskolin-stimulated cyclic adenosine mono phosphate (cAMP) production.
      Efficacies and potencies of these ligands were determined relative to the
      endogenous ligand beta-endorphin and the common mu agonist, morphine. RESULTS:
      Among the ligands studied naltrexone, WIN 44,441 and SKF 10047, were classified
      as antagonists, while the remaining ligands were agonists. Agonist efficacy was
      assessed by determining the extent of inhibition of forskolin-stimulated cAMP
      production. The rank order of efficacy of the agonists was fentanyl =
      hydromorphone = beta-endorphin > etorphine = lofentanil = butorphanol = morphine
      = nalbuphine = nalorphine > cyclazocine = dezocine = metazocine >or= xorphanol.
      The rank order of potency of these ligands was different from that of their
      efficacies; etorphine > hydromorphone > dezocine > xorphanol = nalorphine =
      butorphanol = lofentanil > metazocine > nalbuphine > cyclazocine > fentanyl >
      morphine >>>> beta-endorphin. CONCLUSION: These results elucidate the relative
      activities of a set of opioid ligands at mu opioid receptor and can serve as the
      initial step in a systematic study leading to understanding of the mode of action
      of opioid ligands at this receptor. Furthermore, these results can assist in
      understanding the physiological effect of many opioid ligands acting through mu
      opioid receptors.

PMID- 12513699
TI  - Lipopolysaccharide enhances the cytotoxicity of 2-chloroethyl ethyl sulfide.
AB  - BACKGROUND: The bacterial endotoxin, lipopolysaccharide (LPS), is a well
      characterized inflammatory factor found in the cell wall of Gram-negative
      bacteria. In this investigation, we studied the cytotoxic interaction between 2
      chloroethyl ethyl sulfide (CEES or ClCH2CH2SCH2CH3) and LPS using murine RAW264.7
      macrophages. CEES is a sulfur vesicating agent and is an analog of 2,2'
      dichlorodiethyl sulfide (sulfur mustard). LPS is a ubiquitous natural agent found
      in the environment. The ability of LPS and other inflammatory agents (such as TNF
      alpha and IL-1beta) to modulate the toxicity of CEES is likely to be an important
      factor in the design of effective treatments. RESULTS: RAW 264.7 macrophages
      stimulated with LPS were found to be more susceptible to the cytotoxic effect of
      CEES than unstimulated macrophages. Very low levels of LPS (20 ng/ml)
      dramatically enhanced the toxicity of CEES at concentrations greater than 400
      microM. The cytotoxic interaction between LPS and CEES reached a maximum 12 hours
      after exposure. In addition, we found that tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1-beta (IL-1-beta) as well as phorbol myristate acetate
      (PMA) also enhanced the cytotoxic effects of CEES but to a lesser extent than
      LPS. CONCLUSION: Our in vitro results suggest the possibility that LPS and
      inflammatory cytokines could enhance the toxicity of sulfur mustard. Since LPS is
      a ubiquitous agent in the natural environment, its presence is likely to be an
      important variable influencing the cytotoxicity of sulfur mustard toxicity. We
      have initiated further experiments to determine the molecular mechanism whereby
      the inflammatory process influences sulfur mustard cytotoxicity.

PMID- 12513700
TI  - SeqVISTA: a graphical tool for sequence feature visualization and comparison.
AB  - BACKGROUND: Many readers will sympathize with the following story. You are
      viewing a gene sequence in Entrez, and you want to find whether it contains a
      particular sequence motif. You reach for the browser's "find in page" button, but
      those darn spaces every 10 bp get in the way. And what if the motif is on the
      opposite strand? Subsequently, your favorite sequence analysis software informs
      you that there is an interesting feature at position 13982-14013. By
      painstakingly counting the 10 bp blocks, you are able to examine the sequence at
      this location. But now you want to see what other features have been annotated
      close by, and this information is buried several screenfuls higher up the web
      page. RESULTS: SeqVISTA presents a holistic, graphical view of features annotated
      on nucleotide or protein sequences. This interactive tool highlights the residues
      in the sequence that correspond to features chosen by the user, and allows easy
      searching for sequence motifs or extraction of particular subsequences. SeqVISTA
      is able to display results from diverse sequence analysis tools in an integrated
      fashion, and aims to provide much-needed unity to the bioinformatics resources
      scattered around the Internet. Our viewer may be launched on a GenBank record by
      a single click of a button installed in the web browser. CONCLUSION: SeqVISTA
      allows insights to be gained by viewing the totality of sequence annotations and
      predictions, which may be more revealing than the sum of their parts. SeqVISTA
      runs on any operating system with a Java 1.4 virtual machine. It is freely
      available to academic users at http://zlab.bu.edu/SeqVISTA.

PMID- 12513701
TI  - Mitochondrial defects in cancer.
AB  - Mitochondria play important roles in cellular energy metabolism, free radical
      generation, and apoptosis. Defects in mitochondrial function have long been
      suspected to contribute to the development and progression of cancer. In this
      review article, we aim to provide a brief summary of our current understanding of
      mitochondrial genetics and biology, review the mtDNA alterations reported in
      various types of cancer, and offer some perspective as to the emergence of mtDNA
      mutations, their functional consequences in cancer development, and therapeutic
      implications.

PMID- 12513702
TI  - Estimation of health effects of prenatal methylmercury exposure using structural
      equation models.
AB  - BACKGROUND: Observational studies in epidemiology always involve concerns
      regarding validity, especially measurement error, confounding, missing data, and
      other problems that may affect the study outcomes. Widely used standard
      statistical techniques, such as multiple regression analysis, may to some extent
      adjust for these shortcomings. However, structural equations may incorporate most
      of these considerations, thereby providing overall adjusted estimations of
      associations. This approach was used in a large epidemiological data set from a
      prospective study of developmental methyl-mercury toxicity. RESULTS: Structural
      equation models were developed for assessment of the association between
      biomarkers of prenatal mercury exposure and neuropsychological test scores in 7
      year old children. Eleven neurobehavioral outcomes were grouped into motor
      function and verbally mediated function. Adjustment for local dependence and item
      bias was necessary for a satisfactory fit of the model, but had little impact on
      the estimated mercury effects. The mercury effect on the two latent
      neurobehavioral functions was similar to the strongest effects seen for
      individual test scores of motor function and verbal skills. Adjustment for
      contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates
      only marginally, but the mercury effect could be reduced to non-significance by
      assuming a large measurement error for the PCB biomarker. CONCLUSIONS: The
      structural equation analysis allows correction for measurement error in exposure
      variables, incorporation of multiple outcomes and incomplete cases. This approach
      therefore deserves to be applied more frequently in the analysis of complex
      epidemiological data sets.

PMID- 12513703
TI  - Host-specific cues cause differential attractiveness of Kenyan men to the African
      malaria vector Anopheles gambiae.
AB  - BACKGROUND: Many studies have suggested that variability in the attractiveness of
      humans to host-seeking mosquitoes is caused by differences in the make-up of body
      emanations, and olfactory signals in particular. Most investigations have either
      been laboratory-based, utilising odour obtained from sections of the body, or
      have been done in the field with sampling methods that do not discriminate
      between visual, physical and chemical cues of the host. Accordingly, evidence for
      differential attractiveness based on body emanations remains sparse in spite of
      the far-reaching epidemiological implications of this phenomenon. METHODS: A new
      three-port olfactometer that accommodates complete human beings as sources of
      host-seeking stimuli was used to study behavioural responses of Anopheles gambiae
      Giles sensu stricto (hereafter An. gambiae) under semi-field conditions in
      western Kenya. Differential attractiveness of nine male Kenyans was assessed by
      simultaneously exposing the mosquitoes to (a mixture of) total body emanations of
      3 people occupying separate tents. Controls (empty tents) were included and the
      effect of residual odours following tent occupation was also examined. RESULTS:
      Trap catches increased significantly (P < 0.001) when a tent was occupied. Based
      on 'competition' experiments, the nine persons were classified into least, medium
      and most attractive groups. There was no significant interaction between person
      and trap (P = 0.302) or person and test period (P = 0.223). Presence (P < 0.001)
      or absence (P = 0.949) of significant differences in the number of mosquitoes
      caught per trap when tents were simultaneously occupied by one person in each or
      left empty, respectively, demonstrated that residual odours following tent
      occupation did not affect behavioural responses of the mosquitoes. CONCLUSION: We
      provide evidence that in the vicinity of humans, when exposed to a blend of
      physical and olfactory signals from more than one host, An. gambiae can
      effectively and consistently express host-selection behaviour that results in non
      random biting.

PMID- 12513704
TI  - DNA databanks and consent: a suggested policy option involving an authorization
      model.
AB  - BACKGROUND: Genetic databases are becoming increasingly common as a means of
      determining the relationship between lifestyle, environmental exposures and
      genetic diseases. These databases rely on large numbers of research subjects
      contributing their genetic material to successfully explore the genetic basis of
      disease. However, as all possible research questions that can be posed of the
      data are unknown, an unresolved ethical issue is the status of informed consent
      for future research uses of genetic material. DISCUSSION: In this paper, we
      discuss the difficulties of an informed consent model for future ineffable uses
      of genetic data. We argue that variations on consent, such as presumed consent,
      blanket consent or constructed consent fail to meet the standards required by
      current informed consent doctrine and are distortions of the original concept. In
      this paper, we propose the concept of an authorization model whereby participants
      in genetic data banks are able to exercise a certain amount of control over
      future uses of genetic data. We argue this preserves the autonomy of individuals
      at the same time as allowing them to give permission and discretion to
      researchers for certain types of research. SUMMARY: The authorization model
      represents a step forward in the debate about informed consent in genetic
      databases. The move towards an authorization model would require changes in the
      regulatory and legislative environments. Additionally, empirical support of the
      utility and acceptability of authorization is required.

PMID- 12513705
TI  - [Hematopoietic inhibitors elaborated by bone marrow endothelial cells].
AB  - In this study, the roles of hematopoietic inhibitors elaborated by bone marrow
      endothelial cells in the proliferation and differentiation of hematopoietic
      progenitors were investigated. Murine bone marrow endothelial cell conditioned
      medium (BMEC-CM) was collected and the components with > 10 kD and < 10 kD were
      obtained by centrifugal ultrafiltration. The effect of BMEC-CM and its components
      on proliferation of hematopoietic progenitors was evaluated by CFU-GM and HPP-CFC
      assay and antibody neutralization test. The expression of the inhibitors in BMEC
      and BMEC-CM was detected by RT-PCR and Western blot, and change of proliferation
      and differentiation-related genes during expansion of hematopoietic progenitors
      was examined by membrane hybridization technique. THE RESULTS: (1) When BME C-CM
      and its components directly were added to CFU-GM and HPP-CFC culture system, BMEC
      CM had no effect on colony formation, > 10 kD component enhanced and < 10 kD
      component inhibited the formation of CFU-GM and HPP-CFC. (2) When BMEC-C M and
      its components were added to liquid culture system of marrow cells, after 24
      hours incubation, CFU-GM decreased and HPP-CFC increased significantly in B MEC
      CM group, CFU-GM increased and HPP-CFC had no significant change in > 10 kD
      component group; and both CFU-GM and HPP-CFC reduced in < 10 kD group. (3) MIP-2,
      MIP-1 alpha, MSP, TGF-beta, TNF-alpha, IFN-gamma and T beta 4 were expressed in
      murine marrow endothelial cells, and MIP-2, MIP-1 alpha, MSP, TGF-beta, TNF-alpha
      and T beta 4 were existed in BMEC-CM. (4) Antibody neutralization test results
      demonstrated that TGF-beta, MSP, MIP-1 alpha, IFN-gamma and T beta 4 existed in
      BMEC-CM had significant suppressive effects on CFU-GM and HPP-CFC. (5) T beta 4
      combined with 5 hematopoietic cytokines (SCF, IL-3, IL-6, GM-CSF and EPO) added
      to CD34(+) cells expansion culture system, HPP-CFC significantly increased
      compared with 5 cytokines group. T beta 4 could downregulated the expression of
      proliferation and differentiation-related genes and signal transduction-related
      genes. It is concluded that BM EC-CM promotes the proliferation of early
      hematopoietic progenitor cells, and this effect is related with the inhibitors
      existed in BMEC-CM and it could be executed via influencing cell proliferation
      and differentiation-related genes and signal-related genes.

PMID- 12513706
TI  - [Study on granulocytes derived from induction of committed differentiation of
      hematopoietic stem/progenitor cells ex vivo].
AB  - To evaluated the feasibility of preventing infection after high dose chemotherapy
      and radiotherapy using the granulocytes derived from differentiated from
      hematopoietic stem/progenitor cells ex vivo, human CD34-positive cells were
      isolated from umbilical cord blood by using a high-gradient magnetic cell sorting
      system (MACS), and the cells committedly differentiated with hematopoietic
      cytokines (SCF + IL-3 + IL-6 + G-CSF) in a liquid culture system. The expanded
      cell number, ratio of the viable cells, chromosome and phenotype of the
      differentiated cells and safety analysis of expanded cells were detected by using
      cell count, trypan blue exclusion test, karyotype analysis, flow cytometry and
      tumorigenic model of nude mice, respectively. The results showed that the
      combination of cytokines increased cell number by (1006.4 +/- 103.2) folds and
      flow cytometric analysis showed myeloid marker CD11b expressed in the about 60%
      cells. The growth peak of differentiated cells was at 14 days of culture and
      decreased at about 33 days. No abnormality was found in the karyotype analysis of
      expanded cells. No tumor was found in the nude mice injected with expanded cells
      after 35 days and the expanded cells had the ability of phagocytizing bacteria.
      It is concluded that the cells, differentiated from CD34(+) cells, expanded ex
      vivo possess the function of granulocyte and it was safe for clinical trial.

PMID- 12513707
TI  - [Proliferation and IFN-gamma secretion of autologous T lymphocytes stimulated by
      myeloid leukemia cells induced with rhGM-CSF and rhIL-4].
AB  - To observe the proliferation of T lymphocytes stimulated by CML and AML cells
      which were induced by rhGM-CSF and rhIL-4, and the secretion of IFN-gamma from
      proliferated T lymphocytes, the expression of CD80, CD86 and HLA-DR on CML and
      AML cells induced by GM-CSF and IL-4 was assayed by flow cytometry in vitro. Then
      one-way mixed lymphocyte reaction was carried out, with induced leukemia cells as
      stimulating cells and auto-T lymphocytes as reactive cells. The secretion of IFN
      gamma from T lymphocytes was determined by double antibody sandwich ELISA. The
      results showed that GM-CSF and IL-4 significantly upregulated the expression of
      CD80, CD86 and HLA-DR on CML cells and CD80 and CD86 on AML cells, which could
      stimulate the T lymphocyte proliferation and high secretion of IFN-gamma (in CML
      group) of autologous T lymphocytes. It is concluded that the CML and AML cells
      induced by GM-CSF and IL-4 have the ability to present tumor specific antigen to
      auto-T lymphocyte.

PMID- 12513708
TI  - [Effects of retinoic acid on adhesion molecules expression and adhesive function
      in murine bone marrow stromal cell].
AB  - To explore the effect of retinoic acid (RA) on the expression of intercellular
      adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in
      murine bone marrow stromal cell (BMSC) and adhesive rate of human cord blood
      mononuclear cell (UCBMNC) to BMSC in vitro, the express ions of ICAM-1 and VCAM-1
      of murine BMSC were detected by flow cytometry and the binding capacity of UCBMNC
      to BMSC was tested by MTT assay after co-culturing with 0.1, 1.0 and 10.0 micro
      mol/L RA, respectively. The results showed that 1.0 and 10.0 micro mol/L RA
      increased the expression of ICAM-1 and the adhesive rate of U CBMNC to BMSC,
      however, RA did not induced the increase of expression of VCAM-1. It was positive
      correlation between the increments of ICAM-1 expression and the adhesive rate (r
      = 0.7883, P < 0.05). It is concluded that RA up-regulated ICAM-1 expression of
      BMSC and increased the adhesion of UCBMNC to BMSC in vitro. These may clarify the
      correlation between adhesion molecules on BMSC and homing of hematopoietic stem
      cells, and provide the experimental basis for RA to promote the homing of
      umbilical cord blood stem cell.

PMID- 12513709
TI  - Death style and respiratory burst of neutrophils in peripheral blood and
      pulmonary alveolus under endotoxemia in rats.
AB  - To study the difference of changes on apoptosis, necrosis and respiratory burst
      of the polymorphonuclear neutrophils (PMN) in endotoxemia rat model. LPS
      (O(55)B(5), 5 mg/kg) was injected into abdominal cavity of 20 random normal
      Wistar rat. 2, 4, 8 and 12 hours after injection, the changes of apoptosis,
      necrosis and respiratory burst of the rats between PMN from the peripheral blood
      and from the bronchoalveolar lavage fluid were observed using the flow cytometer.
      At the same time, 5 uninjected rats were taken as control. The results
      demonstrated that the quantity proportions of apoptosis of PMN between the
      peripheral blood PMN and the bronchoalveolar lavage fluid PMN in rat's
      endotoxemia were similar. However, comparison with the uninjected LPS rat, the
      necrosis of peripheral blood PMN obviously increased and the respiratory burst
      capacity was clearly inhibited. Contrarily, the necrosis of bronchoalveolar
      lavage fluid PMN obviously decreased and the respiratory burst obviously
      increased in the injecting LPS rat. It was concluded that the necrosis and
      apoptosis displayed differently between the pulmonary and peripheral blood PMNs
      in endotoxemia. Under state of inflammation, the surviving PMN in tissue
      increased and kept the activated state due to tissue injury.

PMID- 12513710
TI  - [Cloning, expression and biological activity identification of a cDNA encoding
      the extracellular region of human b7-2].
AB  - As one important member of B7/CD28/CTLA-4 costimulatory signal pathway, B7-2
      molecule plays a critical role in regulating T-cell response. In order to further
      explore its effects on regulation of T cell activation, proliferation and
      associated signal pathways, the cDNA encoding extracellular region of human B7-2
      was amplified via PCR and subcloned into some prokaryotic expression vectors to
      express target protein in host strains. The expressed protein was identified with
      Western blot and MTT. Results showed that after screening, the expression level
      of the protein of interest attained the yield of over 20% total bacterial protein
      by using pGEX-4T-2 vector and E. coli BL21 (DE3)-CodonPlus-RIL host cells. The
      recombinant protein could specially react with B7-2 McAb and could stimulate T
      cell proliferation combined with anti-CD3 antibody. In conclusion, the
      recombinant protein was bioactive, therefore the study will make it possible for
      the research of relationship between B7-2 structure and its function.

PMID- 12513711
TI  - [The identical effects of B7-1 and B7-2 on regulation of human IL-2 gene
      transcription factors NF-kappa B and AP-1].
AB  - To detect effects of B7 co-stimulation on cytokines, especially on IL-2 mRNA and
      transcription factors NF-kappa B and AP-1, antiB7-1 McAb, antiB7-2 McAb and C TLA
      4 Ig were added into mixture lymphocyte reaction (MLR) system to block B7/C D28
      signal transduction, IL-2 mRNA and IL-4 mRNA were determined by using competitive
      PCR and IFN-gamma mRNA by using semi-quantitative PCR. MHC class II molecules and
      B7 transfectants were used to stimulate CD28(+) T cell, effects of B7 on NF-kappa
      B and AP-1 were detected by DNA-protein binding assay. The results showed that IL
      2, IL-4 and IFN-gamma mRNA were significantly lower when blockade of B7-2 in MLR
      than blockade of B7-1. Synergistic effects could be seen with combination of two
      or three antibodies. One to six hours after MLR, tDR7 alone induced NF-kappa B
      binding activity; cotransfecting B7 no significantly difference at early time
      point. After 6 hours, induction of tDR7 was decreased whereas B7 prolonged the
      induction of NF-kappa B till 72 hours. tDR7 alone also upregulated AP-1 binding
      activity, on the contrary to NF-kappa B, co-transfecting B7-1 and B7-2 decreased
      AP-1 binding activity within 24 hours. But during 48 - 72 hours, B7 also
      prolonged the AP-1 binding activity. It is concluded that after MLR, B 7
      increased IL-2 secretion by decreasing the degradation of IL-2 mRNA and
      upregulating IL-2 transcription factors. B7 also induced several kinds of
      cytokines secretion. Effects of B7-1 and B7-2 had no significant difference on
      transcription factors. It is suggested that the different functions between B7-1
      and B7-2 maybe related to the difference of cell expression and kinetics. To
      study the molecular mechanism of B7 mediated T cell immune tolerance can help us
      to design a better clinic schema to prevent transplantation rejection and GVHD.

PMID- 12513712
TI  - [A comparison between immunophenotypes of lymphoid cells from human umbilical
      cord blood and bone marrow and its significance].
AB  - To compare the expression of CD antigens on immune cells from umbilical cord
      blood (UCB) and bone marrow (BM) and analyze its clinical significance, the
      phenotypes of lymphoid cells and nucleated cells from 38 UCB and 10 BM samples
      were investigated by flow cytometry with double labeling monoclonal antibodies.
      The results showed that the immature lymphocytes (CD3(-) CD4(+)) were detected in
      UCB and higher than those in BM; cytotoxic T lymphocytes (CD3(+) CD16(+) CD56(+))
      in UCB were significantly lower than those in BM. NK cells (CD3(-) CD16(+)
      CD56(+)) in UCB were higher than those in BM. The ratio of CD34(+) cells in
      nucleated cells of UCB was similar to that of BM, however, both the contents of
      myeloid (CD34(+) CD13(+) and CD34(+) HLA-DR(+)) and lymphoid (CD34(+) CD19(+))
      progenitor cells in UCB were lower than those in BM. It is concluded that the
      immune cells in UCB possess immaturity, which might lead to mild GVHD after UCB
      transplantation. It is inferred from the higher ratio of NK cells in UCB, GVL
      will not decrease after UCB transplantation. The lower contents of myeloid and
      lymphoid progenitor cells in UCB probably accounted for the slow hematopoiesis
      and immune reconstitution following UCB transplantation.

PMID- 12513713
TI  - [Effect of human telomerase reverse transcriptase gene antisense
      oligodeoxynucleotide on telomerase activity in leukemia cells].
AB  - To explore the effect of human telomerase reverse transcriptase (hTERT) gene
      antisense oligodeoxynucleotide (ASODN) on telomerase activity in primary acute
      myeloid leukemia (AML) cells and chronic myeloid leukemia (CML) cells, polymerase
      chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) was used to
      determine telomerase activity. The expression levels of hTERT protein were
      assayed by flow cytometry using immunofluorescence labeling. Immunofluorescence
      assay showed that the expression levels of hTERT protein in AML and CML cells
      decreased with time after hTERT ASODN treatment. There was no difference in hTERT
      protein levels between control and sense oligodeoxynucleotide (SODN)-treated
      cells. Telomerase activity decreased when AML and CML cells were treated with
      ASODN for 48 h. Telomerase activity of AML and CML cells was significantly
      inhibited when the cells treated with ASODN for 72 h. There was no difference in
      telomerase activity levels between control and hTERT SODN-treated cells. It was
      concluded that hTERT ASODN could inhibit hTERT protein expression level, thus
      decreasing the telomerase activity in primary AML and CML cells.

PMID- 12513714
TI  - [Effect of p53 gene on telomerase activity and hTERT gene expression in HL-60
      cells].
AB  - To investigate the change of telomerase activity and human telomerase reverse
      transcriptase (hTERT) gene expression in HL-60 cells transfected with wild type
      p53 gene, wild type p53 gene was introduced into HL-60 cells by Lipofectin
      transfection. Apoptosis was analyzed by TUNEL assay. Telomerase activity and the
      level of hTERT mRNA were detected by telomeric repeat amplification protocol
      (TRAP)-ELISA and RT-PCR, respectively. The results showed that the apoptotic rate
      of HL-60-pN53cG cells was 8.3% and 21.0% respectively after cultured at 32.5
      degrees C for 24 h and 72 h. The level of hTERT mRNA was decreased to 68.4% and
      55.8% and telomerase activity to 27.3% and 8.9% of control value in HL-60-pN53cG
      cells at the same points. In conclusions, hTERT mRNA and telomerase activity were
      down-regulated in HL-60 cells transfected with p53 gene. This may be one of
      mechanisms of apoptosis induced by wild type p53 gene.

PMID- 12513715
TI  - [Effect of G-CSF and GM-CSF on expression of TNF-alpha mRNA and CD69 and
      secretion of IgG in peripheral blood mononuclear cells from systemic lupus
      erythematosus patients].
AB  - In order to understand the effect of hematopoietic stem cell mobilization agents,
      G-CSF and GM-CSF, on the expression of TNF-alpha mRAN and CD69 and secretion of
      IgG in SLE patients' peripheral blood mononuclear cells (PBMNC), expression of
      TNF-alpha mRNA and CD69 was measured by RT-PCR and flow cytometry, respectively,
      and IgG secretion by ELISA. The results showed that 0.1 - 2.0 microg/ml G-CSF did
      not affect the expression of TNF-alpha mRNA in active and static patients' PBMNC
      treated with 0.1 - 2.0 microg/ml cytokines, and 2.0 microg/ml GM-CSF increased
      the expression of TNF-alpha mRNA in active patients' PBMNC. G-CSF and GM-CSF did
      not interfere the expression of CD69 in active and static patients' PBMNC,
      however, the expression of CD69 was significantly increased in active patients'
      PBMNC treated with GM-CSF at more than 8 microg/ml. There was no obvious change
      of IgG secretion from PBMNC induced with 10 microg/ml G-CSF, while the IgG
      secretion was stimulated by 10 microg/ml GM-CSF. It was concluded that G-CSF as a
      mobilization agent could be safe to SLE patients, but GM-CSF may cause some
      harmful effects to patients because of the increase of the parameters relating to
      activity of lupus in active SLE patients.

PMID- 12513716
TI  - [Expression and purification of recombinant glycoprotein (GP) IIb/IIIa receptor
      antagonists].
AB  - To investigate the effect of GST-KGDX (glutathione S-transferase-Lys-Gly-Asp-X)
      fusion protein, GP IIb/IIIa receptor antagonist, on platelet function in vitro.
      The KGDX (Lys-Gly-Asp-X) gene was assembled from 2 synthetic oligonucleotides, 36
      bp in length, using BamH I and Xho I restriction enzyme sites at the end of the
      gene for cloning into the expression vector pGEX4T-1. Expression of fusion
      protein was directed by the tac promoter. The Escherichia coli DH5a contained the
      plasmid pGEX-4T-1-KGDX was expressed by 37 degrees C heat induction. The fusion
      protein of KGDX with glutathione S-transferase (GST-KGDX) was purified in one
      step from the bacterial lysate by glutathione-agarose beads for affinity
      chromatography. GST-KGDX was found to be soluble and abundant, the yield of 35
      mg/L of cultures was obtained. The GST-KGDX was expressed in E. coli to a level
      of 48.02% of total cellular protein. GST-KGDX inhibited ADP-induced human
      platelet aggregation stronger than GST (P < 0.05 or < 0.01). In flow cytometry
      assay for fibrinogen binding, both GST and GST-KGDX inhibited platelet
      aggregation by binding with high affinity to GPIIb/IIIa. Mean fluorescence
      intensity of GST-KGDX fusion protein was significantly higher than that of GST.
      It is concluded that the GST-KGDX fusion protein can be produced by E. coli and
      used as an antiplatelet agent.

PMID- 12513717
TI  - [Molecular cloning of human vWF/A1 gene and its expression].
AB  - To study the mechanism of thrombogenesis and search new anti-thrombotic agent,
      the cDNA for human vWF A1 domain was high-level expressed in E. coli and
      recombinant protein of vWF A1 with biologic activity was obtained. The gene
      encoding A1 domain was amplified by PCR from plasmid containing full length cDNA
      of human vWF. After confirming by DNA sequencing analysis, the recombinant
      expression plasmid pQE31-vWF/A1 was constructed and introduced into E. coli M15
      strain, then induced by IPTG; the expressed protein was purified with Ni-NTA
      agarose, identified by Western blotting. The results showed that the 854 bp DNA
      fragment was obtained by PCR from the plasmid containing full length cDNA for
      human vWF and its sequence was identical to the published sequence. High level
      expression of A1 protein was yielded after 5 hour-induction, which amounted to
      30% of total bacteria protein in inclusion body. Western blot demonstrated it
      possessed good antigenicity and high specificity. It is concluded that cDNA for
      vWF/A1 had been cloned successfully, high level expression of A1 protein was
      achieved in E. oli. This study will provide a basis for the further clinical and
      basic research on the role of vWF in thrombosis and hemostasis.

PMID- 12513718
TI  - [Evaluation of the STA-R analyzer for the study of neonatal and pediatric
      hemostasis].
AB  - To evaluate the capacities of adaptation of the STA-R analyzer (Diagnostica
      Stago, Asnieres, France) to the study of pediatric hemostasis, classical studies
      were undertaken and they have included: (1) Within-run assays (n = 21, 2 control
      levels) and day-to-day precision studies (n = 20, 2 control levels) for the
      following tests: prothrombin time (PT), activated partial thromboplastin time
      (APTT), factor II (FII), factor VII + X (FVII + X), factor V (FV), fibrinogen
      (fg) and antithrombin (AT); (2) Comparison of the results of APTT, FII, FVII + X,
      FV and fg assays (in 50 plasmas) obtained with STA-R and STA (analyzer currently
      used, in our pediatric laboratory). Specific pediatric evaluation has included:
      (1) Evaluation of the STA-R results for low concentrations of the coagulation
      factors; (2) Determination of the lowest dead volume; (3) Introduction of
      peculiar samples among "routine" series. The results showed that within-run
      assays and day-to-day precision studies have confirmed the good performances of
      the STA-R. The comparison of the STA-R and STA results from 50 plasmas shows a
      correlation coefficient of 0.990, 0.995, 0.996, 0.997 and 0.996 for APTT, fg,
      FII, FVII + V and FV respectively. Such results are confirmed for low
      concentrations of coagulation factors. The acceptable dead volume could be
      lowered down to 50 microliters. Very small samples, selected assays and
      emergencies could be easily introduced among routine series. It is concluded that
      the STA-R showed very good technical performances. The STA-R is adapted to the
      routine tests as well as to the very specific samples of neonates and children.

PMID- 12513719
TI  - [Successful engraftment of T-cell undepleted haploidentical transplants by donor
      primed with G-CSF and additional use of ATG and MMF for recipients].
AB  - Seventeen patients and their family donors HLA 2 - 3 antigen mismatched of 2 - 3
      loci were enrolled in the study of haploidentical transplants from February 1999
      to March 2001. Among patients with leukemia, most patients were classified as
      high risk. Eleven patients with ALL were all in more than second remission but
      one was in relapse. Patients with AML were one in CR1, one in CR2 while 4
      patients with CML were two in CP and two in AP. The male-to-female ratio was 14:3
      and the median age was 15 (range from 8 to 35). Conditioning regimens included
      Ara-C 3.0 g/m(2), 2 times per day x 3 d, on day 7, 6 and 5 pre-transplantation,
      CTX 45 mg/(kg per d) x 2 d on day 5 and 4 pretransplantation. TBI with 1000 cGy
      by 2 fractions on day 2 and 1 pretransplantation. The fresh and unmanipulated
      marrow was infused on day 0. Donors were received G-CSF (Lenograstim) at 3 - 4
      microg/(kg per d) x 7 d. The BM cells were collected on eighth day. In GVHD
      prophylaxis, CSA, MTX, ATG (Antithymocyte globulin, Rabbit Fresenius S) and MMF
      (mycophenolate mofetic) were used in different periods. The dose of CSA was 1.5
      mg/(kg per d) on day 7 to 1 pretransplantation, then 3 mg/(kg per d) from day 1
      pretransplantation. MTX was 15 mg/m(2) on day 1 and 10 mg/m(2) on day 3, 6 and 11
      posttransplantation. ATG was administered day 4 to 1 pretransplantation at 5
      mg/(kg per d) and MMF dose was 1.0 g/d from day 7 posttransplantation. All
      patients established successful engraftment after initial transplantation. The
      median days of neutrophil exceeding 0.5 x 10(9)/L and platelet exceeding 20 x
      10(9)/L were 18 (range 13 - 23) and 20 (range 16 - 32) days, respectively.
      Patients were monitored up to day 100 for the sign of aGVHD. The established
      grades II to IV aGVHD occurred in 5 out of 17 patients (29.4%). Eleven patients
      were surviving at a median follow-up of 13 months (range 3 - 27 months). Six out
      of the 17 patients died those 3 of them died of severe aGVHD, 2 of infection and
      1 of leukemia relapse. Severe regimen-related toxicities were not experienced in
      all patients. The median follow-up period was 13 (range 3 - 27) months. Eleven
      patients were alive in disease-free situation with a Karnofsky performance status
      of 100%. This could be caused by the low overall incidence of aGVHD as a result
      of BM primed with G-CSF. The four-agent of immunosuppressive combined prophylaxis
      against GVHD in different periods may be highly effective.

PMID- 12513720
TI  - [Selection of donor in mismatched hematopoietic stem cell transplantation by
      CREG, residue match and HLA three-dimensional structure].
AB  - After search at hematopoietic stem cell banks for transplant donors, there may be
      several donors matched with given standards. To determine the most appropriate
      donor for a specific patient, the potential donors were analyzed and compared by
      three methods. The first is cross-reactive group (CREG) antigens, which defined
      as the public antigens that shared specific serological reaction patterns. The
      second is residue match theory, which concerned the three residues oriented
      upward toward the T-cell receptor. The third is comparing HLA three-dimensional
      structure models. The results of the three methods were not completely accorded
      in our case. However, some less matched donors could be excluded from the
      candidates and the range of selection was further reduced. It is concluded that
      combined application of three methods would contribute in selecting donor for
      hematopoietic stem cell transplantation in clinics.

PMID- 12513721
TI  - [Significance of serological test of blood group in nonmyeloablative allogeneic
      peripheral blood stem cell transplantation of patients with acute leukemia].
AB  - The purpose of this study is to explore the clinical significance of RBC blood
      group serological test in nonmyeloablative allogeneic peripheral blood stem cell
      transplantation (NAPBSCT) of ABO group incompatibility in 4 patients with acute
      leukemia. ABO and MN blood group of donors and recipients were determined by
      hemagglutination test and Rh blood group by Diana Gel phenotype Rh card. The
      changes of blood group in recipients were observed and implant of donor cells was
      monitored by short tandem repeat-PCR method. The results showed that in 2 cases
      of 4 recipients the marrow cells appeared mixed chimera of donor and recipient
      cells, and blood group changed to donor type in 1 of the 2 cases on 100 days
      after transplantation. In another 2 cases, the marrow cells appeared mixed
      chimera without blood group chimera on 154 days after transplantation, and
      rejection of the transplant occurred in 1 of the 2 cases. The determination of
      hemagglutinin titer showed that the implant rate of donor cells was lower in the
      recipients with higher hemagglutinin titer and blood group chimera did not
      appear, conversely, the implant rate was higher in the recipients with lower
      titer and blood group chimera appeared early. It is concluded that examination of
      RBC blood group in NAPB SCT can indirectly reflect effectiveness of
      transplantation, contribute to decide the intensity of conditioning protocol and
      immunosuppressive therapy after transplantation, estimate prognosis and guide
      blood transfusion during transplantation.

PMID- 12513722
TI  - [The effect of separating red blood cells from bone marrow graft in vitro by
      methylcellulose].
AB  - It has need to separate red blood cells (RBC) from marrow graft in ABO group
      unmatched BMT and auto-BMT with purging tumor cells, the separating effect of
      methylcellulose was observed. The mixture of 0.5% methylcellulose and bone marrow
      was laid up in an open transfusion system, and then sedimentation of RBC was
      performed in the transfusion tube. The separating results of 18 marrow grafts
      showed that the recovery rates of mononuclear cells and CD34(+) cells were (83.8
      +/- 55.2)% and (90.3 +/- 7.2)%, respectively. RBC residual rate was (4.3 +/-
      1.5)%. The yield of CFU-GM was (60.8 +/- 22.4)/2 x 10(5) MNC, and there was no
      difference to [(69.8 +/- 23.4)/2 x 10(5) MNC] yielded from same marrow samples,
      separated by Ficoll-Hypaque separation. It is concluded that this method could be
      used for bone marrow transplantation.

PMID- 12513723
TI  - [Establishment of a murine model for allogeneic umbilical cord blood
      transplantation].
AB  - This study was undertaken to establish a murine model for unrelated allogeneic
      umbilical cord blood transplantation (UCBT). The characteristics and percentage
      of hematopoietic stem/progenitor cells between near-term fetal and neonatal
      murine peripheral blood (FNPB) and bone marrow (BM) were evaluated by flow
      cytometry and semisolid methylcellulose culture. BABL/c (H-2(d)) recipient mice
      conditioned with high dose CTX were transplanted with FNPB form C57BL/6 (H-2(b))
      mice and the survival rate, hematopoietic and immunological reconstruction, graft
      versus host disease (GVHD) and engraftment level were observed. The results
      showed that the numbers of day 14 CFU-GM and CFU-GEMM in FNPB (176.40 +/- 78.39)%
      and (141.40 +/- 56.57)%, respectively were much higher than those in BM (75.20 +/
      26.41)% and (68.80 +/- 23.95)%, respectively. Moreover the percentage of Sca
      1(+) CD34(+) cell subsets in FNPB (3.63 +/- 1.13)% was also higher than that in
      BM (1.41 +/- 0.8 7)%. FNPB transplantation improved survival rate and
      reconstituted hematopoietic and immune function in recipients. There was no
      evidence of GVHD. Chimeric analysis showed that the proportion of donor cells in
      BM of recipients was 27.94% at 21 days after transplantation. It was concluded
      that FNPB contains more hematopoietic stem and progenitor cells with high
      expansion ability and weak allogeneic immunity, which was similar to human UCB.
      The murine model for allogeneic UCBT (C57BL/6-->BALB/c) was established
      successfully.

PMID- 12513724
TI  - Clinical assessment of preventing febrile nonhemolytic transfusion reaction by
      leukocyte-depleted blood transfusion.
AB  - The objective was designed to assess the clinical efficiency of preventing
      febrile nonhemolytic transfusion reactions (FNHTR) with transfusion of leukocyte
      depleted RBC and platelet concentrates. One hundred patients with cirrhosis of
      liver, gastric ulcer and cancer were selected to receive RBC concentrates with
      leukocyte filtration. Another group of 50 patients with liver necrosis, gastric
      ulcer and cancer were selected to receive non-filtered RBC concentrates. Two
      hundred and forty patients with acute or chronic leukemia, aplastic anemia,
      multiple myeloma, thrombocytopenia purpura, diabetes mellitus, cirrhosis of
      liver, upper gastrointestinal hemorrhage, severe hepatitis, burn and cancer post
      radioactive or chemical treatment were divided into two group with 120 patients
      in each one and selected randomly to receive platelet concentrates. The incidence
      rates of FNHTR in all patients were investigated. Results showed that there was
      no FNHTR in 100 transfusions with leukocyte-depleted RBC concentrates. Eight out
      of 50 patients with non-filtrated RBC concentrates showed FNHTR. The incidence of
      FNHTR was sixteen (16%) in non-filtrated transfusion. Twenty-five and 7 patients
      manifested FNHTR respectively in non-filtrated or filtrated platelets
      transfusions. The incidence of FNHTR was 20.83% and 5.83% respectively in non
      filtrated or filtrated platelet transfusion. It is concluded that leukocyte
      depleted RBC and platelet concentrates reduces FNH TR in blood transfusion.

PMID- 12513725
TI  - [Change of platelet count and P-selectin in preserved platelet concentrates].
AB  - To observe the change of quantity and quality of platelets preserved in a full
      sealed bag, and explore the difference of platelets preserved in oscillating and
      static conditions at (22 +/- 2) degrees C, the platelet concentrates were
      prepared with a CS-3000-plus blood cell separator, the platelet counts were
      performed with automatic blood cell analyzer and P-selectin in supernatant of
      platelet concentrates was detected by ELISA. The results showed that both of
      platelet count and P-selectin content in the platelet concentrates had no
      significant difference between oscillating and static preservation condition.
      With prolongation of preserved time, the platelet count decreased and P-selectin
      content increased gradually in both preserved conditions. There was no difference
      in the platelet counts during 0 - 72 hours preservation in both conditions, and
      significant difference was seen in 96 - 120 hours preservation. It was concluded
      that the expired date for platelet product preserved in CS-3000-plus blood cell
      separator full-sealed system should be 3 days. Under the condition of (22 +/- 2)
      degrees C, the quality of the platelet preserved in oscillating state is not
      superior to static preservation.

PMID- 12513726
TI  - [Thermometry of intracellular ice crystal formation in cryopreserved platelets].
AB  - The temperature of platelet intracellular ice crystal formation (IIF) is one of
      the most important physical parameters to instruct platelet cryopreservation. In
      this study, the range of temperatures for platelet IIF was measured by means of
      biological and physical methods. All platelet samples were graded cooling, and
      two samples of per 5 degrees C decrease were thawed by 2 different ways: 37
      degrees C directly (T 37 degrees C) and 37 degrees C after keeping in liquid
      nitrogen (LN) for 2 hours. The phosphatidylserine (PS) positive rate, plasma
      lactate dehydrogenase (LDH) concentration and platelet aggregate rate were
      measured in all samples. The heat release graphs of platelets cryopreserved with
      or without 5% DMSO were also measured by differential scanning calorimeter (DSC).
      The results showed that the PS positive rates and aggregate rates in platelets
      and plasma LDH concentrations gradually increased in T 37 degrees C group and
      decreased in LN group until the arrival of -35 degrees C, and then there were no
      further changes of the 3 parameters. A small second heat release peak was
      detected at about -35 degrees C in the platelet samples cryopreserved without
      DMSO. It is concluded that the temperature of intracellular ice crystal formation
      in platelet is from -30 to -40 degrees C (-35 degrees ).

PMID- 12513727
TI  - [A colorimetric method of HEC toxin hemolysis test for diagnosis of paroxysmal
      nocturnal hemoglobinuria].
AB  - The purpose of the study is to establish a colorimetric method of HEC toxin
      hemolysis test for diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). RBCs
      from normal persons and patients with PNH and non-PNH anemia were treated with
      HEC toxin secreted by Aeromonas hydrophila J-1 strain and the absorbance at 630
      nm was measured to quantitate the extent of hemolysis. The results demonstrated
      that the RBCs from PNH patients showed resistance to the toxin hemolysis, which
      was in accord with the percentages of CD59(-) cells, while the RBCs from normal
      persons and non-PNH anemic patients were nearly totally lysed. It is concluded
      that the method can be considered as a simple, specific and reliable method for
      the diagnosis of PNH.

PMID- 12513728
TI  - The role of cytokines and transcription factors in megakaryocytopoiesis.
AB  - The role of cytokines and transcription factors on the regulation of megakaryocy
      topoiesis and platelet production are reviewed in this article.
      Megakaryocytopoiesis involves the proliferation and differentiation of
      megakaryocytic pro genitor cells into immature megakaryocytes, and the
      differentiation of immature megakaryocytes to mature megakaryocytes which produce
      platelets. The former is regulated mainly by thrombopoietin (TPO) and to a lesser
      degree by other cytokines such as interleukin-1 (IL-1), IL-3 and platelet-derived
      growth factor (PDGF), the later by TPO and probably IL-6 and IL-11. A number of
      transcription factors have been implicated in the control of megakaryocyte
      differentiation. GATA-1, FOG-1 and Fli-1 are essential regulators in early- and
      mid-stages of megakaryocytopoiesis. NF-E2 regulates late-stage of
      megakaryocytopoiesis and platelet production. However, the platelet release
      mechanism is poorly understood. Nitric oxide (NO) may act in the stage of
      platelet release through induction of apoptosis in megakaryocytes.

PMID- 12513729
TI  - [Prognostic factors of childhood acute lymphoblastic leukemia].
AB  - The cure rate for children with acute lymphoblastic leukemia in big treatment
      centers in Western countries is now about 80%. This accomplishment is owe to
      patients successful treatment based on combination of multiagent chemotherapy,
      risk-based intensification of therapy and central nerve system prophylaxis.
      Stratification of patients is according to prognostic factors that predict risk
      of relapse. It is necessary to consider the interrelationship of prognostic
      factors. In host-related factors, which are generally known as age, gender, race,
      and pharmacogenetics. Disease-related factors include white blood cell count,
      immunopheno typing, cytogenetic or molecular genetics features, etc. Treatment
      related factors are what can be modified. Early response to treatment is often
      the strongest prognostic factor. Large, controlled and usually randomized
      clinical trials greatly improve the prognosis of childhood acute lymphoblastic
      leukemia.

PMID- 12513730
TI  - [Plasma thrombopoietin level and its influence on megakaryocytopoiesis in end
      stage liver cirrhosis and uremia patients].
AB  - To clarify the thrombopoietin (TPO) production in patients with end-stage liver
      cirrhosis and uremia under hemodialysis, plasma TPO levels in patients with liver
      cirrhosis (n = 15), uremia under hemodialysis (n = 20) and healthy controls (n =
      40) were measured by using a sandwich enzyme linked immunosorbent assay.
      Relationship between megakaryocytopoiesis and plasma TPO levels was analysed by
      linear regression. The results showed that the mean plasma TPO concentration in
      the uremic patients was significantly lower than that in the healthy volunteers,
      whereas plasma TPO level in end-stage liver cirrhosis was not significantly
      different from that of normal controls; plasma TPO levels in liver cirrhosis and
      uremic patients did not significantly influence megakaryocytopoiesis. It is
      concluded that end-stage liver cirrhosis patients maintained normal plasma TPO
      levels, but the production of TPO was significantly reduced in renal failure
      patients. Thrombocytopenia in liver cirrhosis appears to be not related to plasma
      TPO levels.

PMID- 12513731
TI  - [Accelerating hematopoietic recovery in allogeneic bone marrow transplantation
      mice by co-infusion of marrow stromal cells transduced with dual genes of IL-3/IL
      6].
AB  - To observe whether bone marrow stromal cell line QXMSC1 (H-2(d)) engineered to
      secrete IL-3 and IL-6 can improved the hematopoiesis in allogeneic bone marrow
      transplantation (allo-BMT) mice, the stromal cell line QXMSC1IL-3/IL-6 was
      established by QXMSC1 cells transduced with the recombined retrovirus vector
      pL3SN containing mouse IL-3 cDNA and pL6SN containing human IL-6 cDNA. The
      lethally irradiated C57BL/6 (H-2(b)) mice were engrafted with bone marrow cells
      (1 x 10(7) cells/mouse BALB/c mice, H-2(d)) in which T cells were depleted by
      anti-Thy1.2 monoclonal antibody adding complement, and QXMSC1IL-3/IL-6 cells (5 x
      10(5)/mouse) were co-infused at same time. The hematopoiesis of recipient mice
      was observed in 20 and 40 days post-transplantation. Blood RBC and WBC were
      counted, and nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM were assayed in
      recipient bone marrow. Results showed that IL-3 and IL-6 were stably expressed in
      QXMSCQIL-3/IL-6 cells. Compared with BMT and co-infusion with QXMSC1 or QXMSC1
      pLXSN cell groups, co-graft with QXMSC1IL-3/IL-6 cells increased the number of
      blood RBC and WBC in the recipients, and also significantly increased nucleated
      cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM in recipient bone marrow. It is
      concluded that the marrow stromal cells transduced with IL-3/IL-6 cDNA improve
      the hematopoiesis in allo-BMT mice. Co-graft with QXMSC1IL-3/IL-6 cells has
      synergistic effect in accelerating hematopoietic reconstitution.

PMID- 12513732
TI  - [The supportive effect of primary bone marrow stromal cell layers on retroviral
      mediated transduction of human hematopoietic stem/progenitor cells].
AB  - To elucidate the effect of established primary bone marrow stromal layers on the
      gene transduction of human hematopoietic stem/progenitor cells (HSC/HPC),
      mononuclear cells (MNC) from adult bone marrow were isolated by centrifugation on
      Ficoll-Hypaque gradients and plated in stromal culture medium. The cells were
      incubated until passage 4 to establish primary stromal layers. The HSC/HPC
      prestimulated by cytokines were transduced by retroviral supernatant containing
      mdr1 gene in presence of irradiated stroma-contact support. Transduced cells were
      plated in a colony-forming unit assay with and without vincristine (VCR) to
      assess the efficiency of transduction. Individual colonies were also analyzed by
      polymerase chain reaction (PCR) for the presence of provirus. The results showed
      that the mixed adherent cell layers were formed when adult bone marrow stromal
      cells were incubated for four to six weeks, mainly being composed of fibroblasts.
      In the presence of stroma-contact support, the average of gene transduction
      efficiency in marrow-derived progenitors increased 2.1 to 3.3 folds measured by
      colony-forming assay and/or PCR, significantly higher than those without support
      of stroma. It is concluded that the presence of bone marrow stroma support in
      combination with cytokine facilitates augmenting the extent of retroviral
      mediated gene transduction.

PMID- 12513733
TI  - Expression of caspase-3 in CD34+ cord blood cells and its significance.
AB  - To evaluate expression of caspase-3 protein in CD34(+) cells from cord blood (CB)
      and its significance during culture in vitro with various growth factors, RT-PCR,
      Western blot and flow cytometry were used to determine cell proliferation,
      apoptosis and expression of caspase-3 in CD34(+) cells during culture in vitro.
      The results demonstrated that caspase-3 mRNA was constitutively expressed at a
      low level in freshly isolated CD34(+) cells. Expression of caspase-3 mRNA and
      protein was upregulated when these cells were expanded in suspension culture with
      growth factors for 3 days. However, only the 32 kD inactive caspase-3 proenzyme
      was detected in the freshly isolated CD34(+) cells and those cells after 3 days
      expansion with cytokines. Along with the culture time extension (7 days) in
      vitro, especially without early-effective cytokines SCF or FL existence, caspase
      3 was activated and a cleavage 20 kD was detected. It is concluded that the
      caspase-3 is involved in apoptosis of primitive CD34(+) cells during expansion in
      vitro, and early-effective cytokines, SCF and FL, could conserve hematopoietic
      stem cells and suppress apoptosis.

PMID- 12513734
TI  - [Human umbilical cord blood hematopoietic stem/progenitor cells can grow up in
      the mouse liver].
AB  - The biological characterization, differentiation and regeneration of hepatic
      stem/progenitor cells are the one of very active and interested fields. In this
      report, intravenous injection of human umbilical cord blood (HUCB) cells into the
      BALB/c-nu and SCID mice, an animal model for transplantation and liver injury,
      was reported. Using of flow cytometry and tissue typing (HLA), it was found that
      the HUCB cells were survived in mouse liver for 9 weeks. After separation from
      perfused liver, HUCB cells were detected by hematopoietic colonies (CFU-GEM M) in
      hepatocyte culture. It was concluded that the transplanted HUCB hematopoietic
      stem/progenitor cells can be survived in the liver over a long period of time.

PMID- 12513735
TI  - [Study on telomerase activity and expression of hTERT, c-myc and bcl-2 during
      terminal differentiation of HL-60 cells induced by retinoic acid].
AB  - The study was to explore the telomerase activity and the expression of hTERT, c
      myc and bcl-2 mRNA during terminal differentiation of HL-60 cells induced by all
      trans-retinoic acid (ATRA) and to study the possible molecular mechanism. By use
      of the model of differentiated HL-60 cells induced by ATRA, the telomerase
      activity was determined by TRAP-PCR-ELISA and the expression of hTERT, c-myc, bcl
      2 mRNA was detected by RT-PCR in differentiated HL-60 cells. The results showed
      that during differentiation of HL-60 cells, the telomerase activity was
      decreased, the expression of hTERT, c-myc and bcl-2 mRNA was downregulated, and
      the downregulation of hTERT occurred prior to suppression of telomerase activity.
      It is concluded that the telomerase activity is related to decrease expression of
      hTERT, c-myc and bcl-2 mRNA during HL-60 cell differentiation induced by ATRA.

PMID- 12513736
TI  - [Inhibition of K562 cell proliferation by wild type p16 and p53 genes co
      transfection].
AB  - The tumor suppressor gene p53 and p16, both of which play an important role in
      inhibition of tumorigenesis, are homozygously deleted in human myeloid leukemia
      cell line K562. To explore the inhibition of K562 cell proliferation by wild type
      p16 and p53 genes, both p16 and p53 genes were co-transfected into K562 cells
      mediated by liposome. The expression of the two genes was measured by
      immunocytochemical method, the cell cycle was analysed by flow cytometry, and the
      number of recovered viable cells was assessed after transfection. After co
      transfection, the p53 and p16 positive cells were 23% and 28%, respectively. The
      results showed that co-transfection of p16 and p53 genes significantly inhibits
      cell proliferation comparing with transfection either by p16 gene or by p53 gene
      (P < 0.05). Expression of p16 and p53 proteins increased the cell number in G(1)
      phase but decreased the cell number in S phase. It is concluded that co
      transfection of p16 and p53 genes has a stronger growth-inhibitory effect on K562
      cell growth than that of transfection only by p16 gene or by p53 gene, may be a
      pathway for gene therapy in leukemia.

PMID- 12513737
TI  - [Effects of SCL antisense ooligonucleotides on K562 and CEM cell lines].
AB  - The stem cell leukemia (SCL) gene is a new oncogene related with leukemogenesis.
      To explore the effects of antisense oligonucleotides of SCL on leukemic cells,
      SCL antisense phosphorothioate oligodeoxynucleotides (AS-PS-ODN) were used to
      treat K562 and CEM leukemic cell lines to observe the effects on proliferation,
      differentiation, apoptosis and SCL mRNA expression in the cells. The results
      showed that incubation of K562 or CEM cells with AS-PS-ODN at different
      concentrations led to inhibition of cell proliferation, and the inhibitory
      effects varied with the incubation time. The positive rate of benzidine staining
      in K562 cells increased significantly after the inhibition with AS-PS-ODN,
      compared with S-PS-ODN treatment. The characteristics of apoptosis were observed
      in K562 cells treated with AS-PS-ODN, but not in CEM cells. Expression of SCL
      mRNA in K562 and CEM cells and SIL-SCL mRNA in CEM cells decreased after
      incubation of AS-PS-ODN. It is concluded that SCL AS-PS-ODN inhibits specifically
      the proliferation of K562 and CEM cells, also decreases the level of SCL and SIL
      SCL mRNA expression. AS-PS-ODN enhances erythroid differentiation and induces
      premature apoptosis in K562 cells.

PMID- 12513738
TI  - [Inhibition of the activation of transcriptional factor NFkappaB during sodium
      selenite-induced apoptosis in NB4 cells].
AB  - In order to evaluate the effect of sodium selenite on the activation of NFkappaB
      during selenite-induced apoptosis in NB4 cells, Western blot was used to measure
      the level of P65 in nuclear extraction of NB4 cells treated with sodium selenite
      to reflect the activation of NFkappaB; the apoptosis of NB4 cells was determined
      by morphological observation, DNA ladder electrophoresis and flow cytometry; and
      MTT test was used to measure the growth inhibition of cells. Results showed that
      sodium selenite (>/=5 micro mol/L) suppressed the cell growth, induced apoptosis
      and inhibited the activation of NF kappaB in a concentration- and time-dependency
      pattern. It was concluded that inhibition of NF kappaB might be one of the
      mechanisms in selenite-induced apoptosis in NB4 cells.

PMID- 12513739
TI  - Effect of arsenic trioxide on different cell lines derived from chronic myeloid
      leukemia.
AB  - The objective is to explore the effect and the mechanism of arsenic trioxide,
      As(2)O(3), on different cell lines of chronic myeloid leukemia (CML). Different
      concentrations of As(2)O(3) (0.2, 2 and 10 micro mol/L) were added to CML cell
      lines KU812 and MEG-01 and other leukemia cell lines U937 and PL21, the cell
      numbers were counted at different times, TUNEL and DNA ladder were assayed.
      Different antibodies, CD34, CD13, CD33, CD19, CD11b, CD14 and CD7, were added to
      detect the change of the molecules on cell surface, the change of bcr-abl by RT
      PCR and the activity of caspase-3 were assayed. The results showed that different
      concentrations of As(2)O(3) had different effects on the survival of the 4 cell
      lines. After culture for 24 hours with As(2)O(3), there was no significant
      increase in CD11b in all the four cell lines. There were no changes of bcr-abl in
      the two CML cell lines treated and untreated with As(2)O(3) by RT-PCR. Activities
      of caspase-3 were all increased. It is concluded that As(2)O(3) can induce
      apoptosis in CML cell lines, the concentration to induce apoptosis is different,
      CML cell lines are more sensitive than the other 2 leukemia cell lines. As(2)O(3)
      induced apoptosis may have some relation with the activation of caspase-3.

PMID- 12513740
TI  - [Expression of novel cloned genes HC56, HC71 and HC90 mapped on human chromosome
      17p13.3 in leukemic cells].
AB  - In order to investigate expression of novel genes HC56, HC70 and HC90 mapped on
      chromosome 17p13.3 in human leukemic cells, HC56, HC71 and HC90 genes expression
      was examined in cells from 35 patients with acute leukemias and 4 leukemic cell
      lines by using semi-quantitative RT-PCR with incorporation of alpha(32)P dATP,
      betaM2 gene as endogenous control. The results showed that HC90 gene expression
      level was lower in patients with acute lymphocytic leukemia and T lymphocytic
      leukemic cell line Jurkat than that in normal control. Low-level HC71 gene
      expression was detected in acute myeloid leukemia. There was no expression
      difference in HC56 between leukemic cells and normal blood cells. It was
      concluded that both HC70 and HC90 genes were aberrantly expressed in human
      leukemic cells.

PMID- 12513741
TI  - [The application of 4-color fluorescence labeling antibodies and its significance
      in immunophenotyping for leukemia by flow cytometer].
AB  - To prove the significance of 4-color fluorescence labeling flow cytometric
      analysis for leukemia immunophenotyping, bone marrow and peripheral blood samples
      from 88 cases with acute leukemia were analyzed by means of flow cytometry with 4
      color fluorescence labeling monoclonal antibodies (McAbs). More than 90% of cases
      could be classified into acute myeloid, T- or B-lymphocytic leukemia by staining
      with 13 different kinds of monoclonal antibodies within 4 tubes of combination of
      antibodies. AML-M(2) - M(7) could also be identified simultaneously. Another one
      tube of combination of 4 McAbs could be used for further subtyping of those who
      were undetermined by the above 4 tubes. Patients with AML-M(0)/M(1) which may be
      negative of myeloperoxidase (MPO) in cytochemistry can be identified by labeling
      with both membrane and cytoplasmic antibodies. In conclusion, the accuracy of
      leukemia immunophenotyping has been improved by 4-color flow cytometry analysis.

PMID- 12513742
TI  - [Significance of in situ identification of apoptosis and proliferation rates in
      diagnosis of myelodysplastic syndromes].
AB  - In order to investigate the significance of apoptosis and proliferation rates in
      differential diagnosis, evaluating curative effect and leukemia transformation in
      myelodysplastic syndromes, apoptosis index (AI) and proliferating index (PI) were
      assayed in marrow smears from 60 cases of MDS, 30 AML, 21 chronic aplastic anemia
      (CAA), 16 hemolytic anemia, 15 megaloblastic anemia and 30 normal controls. The
      apoptotic cells were assayed with TUNEL technique and proliferating cell nuclear
      antigen (PCNA) by immunohistochemical method in situ. The results showed that
      average AI in marrow smears from 39 cases with MDS prior therapy was (11.2 +/-
      8.8)% and PI was (17.3 +/- 8.7)%, significant differences were observed in MDS
      group and normal control group, as well as in AML, CAA, megaloblastic anemia and
      hemolytic anemia groups. Hypoplastic MDS can be distinguished from CAA by AI and
      PI. Clinical therapy induced significant alteration of AI and PI in MDS, AML and
      CAA. After therapy of MDS, the AI dropped from (11.2 +/- 8.8)% to (6.6 +/- 0.7)%.
      It was concluded that examination of AI and PI of marrow cells in situ may
      provide valuable prognostic information, also can contribute to evaluate
      therapeutic effectiveness.

PMID- 12513743
TI  - [Establishment of models for purging leukemic cells from the grafts in vitro].
AB  - Using a fluorochrome Calcein-AM, leukemia cells were labeled and seeded into cell
      lines or bone marrow cells to establish three cell-models of grafts with
      leukemia. These cell-models were engaged with CD34 immunomagnetic beads and the
      purging efficacy was evaluated using both fluorescence microscopy and flow
      cytometry. The results showed that the cell-models established in this study
      could be evaluated successfully not only with fluorescence microscopy but also
      flow cytometry. After CD34 positive selection, KG1a cells were removed by (0.98
      +/- 0.09) log in model II and NALM-6 cells were removed by (1.82 +/- 0.51) log in
      model III, respectively. It is concluded that the models established in this
      study are stable and direct with an excellent reproducibility and an accuracy,
      which can be used to evaluate purging efficacy of leukemia cells in model graft
      using immunomagnetic selection and the experimental studies on tumorcidal effect
      in vitro.

PMID- 12513744
TI  - [Development of MTS/pms colorimetric assay in the proliferation of leukemic
      cells].
AB  - In order to establish a new more rapid, safe and sensitive colorimetric assay for
      the proliferation of leukemic cells, MTS/pms has been developed. This automated
      colorimetric assay is based on the characteristic of viable and metabolically
      active leukemic cells to cleave MTS/pms into a water-soluble product whose
      optical density is determined at 492 nm by an automated microtiter-plate reader
      photometer. The results indicated that only active leukemic cells cleaved MTS/pms
      into product measured, and dead cells did not reduce MTS/pms. A linear relations
      hip were found between the viable cell number and optical density of MTS/pms
      cleaved by HL-60 and K562 cell (r = 0.963). Compared with MTT and INT assays, the
      reduced product of MTS/pms is water-soluble. It is concluded that MTS/pms
      colorimetric assay is more rapid, accurate and sensitive for the bioassay of
      proliferation of leukemic cells.

PMID- 12513745
TI  - [Construction of expression vector for recombinant annexin II and characteristics
      of its fibrinolysis].
AB  - The study was designed to investigate annexin II resulting in molecular
      pathological mechanism of the primary fibrinolysis and establish annexin II
      vector model for further research on disturbance of coagulation. A target gene
      was amplified from human umbilical vein endothelial cells (HUVEC) by RT-PCR.
      Annexin II gene fragment was purified and ligated with molecular biological
      recombinant technology. The recombinant of plasmid annexin II was transfected
      into HL-60 cells and its distribution in the cell and structure characteristics
      of annexin II protein were evaluated by multi-photon excitation laser scanning
      microscope. By means of flow cytometry (FCM) and Werstern blot technique, the
      protein expression was qualitatively and quantitatively analyzed. Transfected
      cells were treated in vitro with annexin II antisense oligonucleotide (AS)
      targeting to the start site of annexin II cDNA. The results showed that the
      recombinant pZeoSV2(+)/ANN II was constructed successfully and expressed in HL-60
      cells. The protein expression was distributed on the surface of cell by
      fluorescence assay. After transfection for 48 hours, the cells occurred higher
      level of expression. The level of the plasmin was significantly enhanced in the
      present of annexin II. The FCM and Western blot analysis showed the annexin II
      expression was similar both in transiently and stably transfected in HL-60 cells.
      Annexin II antisense oligonucletide and McAb significantly inhibited the activity
      of plasminogen. It was concluded that annexin II plays an important role in the
      fibrinotysis. Annexin II vector was defined as a expression tool for further
      studying fibrinolysis and coagulopathy in malignant disease.

PMID- 12513746
TI  - [A clinical study of haploidentical and G-CSF primed bone marrow transplantation
      by using CD25 for aGVHD prophylaxis].
AB  - To explore the feasibility of using CD25 monoclonal antibody (Basiliximab) in T
      cell undepleted allo-BMT with graft from haplotype-matched related donor for
      acute GVHD prophylaxis. Twenty-eight patients with leukemia received allo-BMT
      from HLA two or three loci mismatched related donors. The donors were given G-CSF
      (Lenograstim) 250 micro g/d for 7 doses prior to marrow harvest. CSA, MTX, ATG
      and mycophenolate mofetil (MMF) were combined for GVHD prophylaxis. ATG 5
      mg/(kg.d) was infused from day 4 to day 1 before transplantation and MMF was
      administered from day 7. In the study group, the patients received additional
      CD25 monoclonal antibody for aGVHD prophylaxis. CD25 20 mg each by 30 min
      intravenous infusion on 2 hours before transplantation and day 4 after
      transplantation was administered while no application of CD25 in the controls.
      The outcomes of transplantation were compared between the stud y and control
      groups. The results showed that the median number of CD34(+) cell in graft was
      5.9 x 10(6)/kg in the control group and 7.9 x 10(6)/kg in the study group. The
      median number of CD3(+) cell was 48 x 10(6)/kg and 52 x 10(6)/kg respectively (P
      > 0.05). All patients showed 100% donor-typed hematopoietic cells after
      transplantation by cytogenetic evidence. Five out of fifteen patients in the
      control group experienced II - IV acute GVHD. While none of thirteen in the study
      group developed the II - IV acute GVHD. However, none in both groups developed
      extensive cGVHD. The median follow-up duration was 8 (3-15) months in the study
      group and 26 (15-36) months in control. In the study group, one patient died from
      transplant related mortality (CMV infection); no one relapsed; and 12/13 patients
      survived in disease-free situation within the period of follow-up. In the control
      group, six patients died from transplant related mortality (3 GVHD, 2 infection
      and 1 relapsed) and 9/15 patients survived in disease-free situation. The one
      year probabilities of disease-free survival (DFS) in two groups were
      significantly different (P < 0.05). It is concluded that the transplant from
      haploidentical donors used CD25 antibody is effective and feasible in preventing
      acute severe GVHD and improving DFS. The major histocompatibility barrier in the
      haploidentical related allo-BMT could be crossed by donors primed with G-CSF and
      GVHD prophylaxis with CD25 antibody in the hosts.

PMID- 12513747
TI  - [Role of interleukin-18 in pathogenesis of acute graft-versus-host disease].
AB  - To investigate the relationship between interleukin-18 (IL-18) and human acute
      graft-versus-host disease (aGVHD), 26 patients undergoing allogeneic peripheral
      blood stem cell transplantation (allo-PBSCT) were included in this study. IL-18
      secreted by peripheral blood mononuclear cells (MNCs) was measured by enzyme
      linked immunosorbent assay (ELISA) before transplantation and during aGVHD. The
      results showed that grade I GVHD and grades III-IV GVHD developed in 10 and 5
      cases, respectively. The levels in the supernatants of MNCs from patients with
      aGVHD were significantly higher than those in the cases without aGVHD. The levels
      of IL-18 were correlated with the severity of aGVHD. It is concluded that IL-18
      plays an important role in the development of aGVHD.

PMID- 12513748
TI  - [Analysis of serologic typing error for HLA-A and HLA-B in Chinese].
AB  - Serological mistypings of HLA-A and HLA-B in 27 cases were analyzed. The results
      showed that for HLA-A and HLA-B typing, the rates of incorrect antigen
      assignments were significantly higher than rates of antigen misses (P < 0.05),
      but there was no significant difference between HLA-A and HLA-B typings. The
      frequencies of miss-assigned HLA-A and HLA-B specificities were A1 (66.7%), A3
      (50.0%), A11 (13.5%), A9 (11.8%), A19 (7.1%), and B16 (50.0%), B48 (43.9%), B15
      (16.7%), B40 (11.1%), B13 (10.0%) and B17 (9.1%). In conclusion, the serologic
      and DNA-based typing techniques should be reciprocally complementary in HLA-A and
      HLA-B typing.

PMID- 12513749
TI  - [Activation of random-donor platelet concentrates and platelet prepared from
      random-donor apheresis collections during storage].
AB  - The activation of random-donor platelet concentrates and platelets prepared from
      random-donor apheresis collections (plateletpheresis) during storage were
      studied. Percentage of CD62p staining and mean channel fluorescence (MCF) of CD41
      of two kinds of platelets during storage on day 0, day 1, day 3 and day 5 were
      determined by flow cytometry. The results showed that percentages of CD62p
      staining and MCF of CD41 in plateletpheresis were (18.91 +/- 6.25)%, (19.48 +/-
      8.27)%, (22.82 +/- 6.06)%, (56.71 +/- 11.79)% and (8.09 +/- 2.38)%, (8.13 +/-
      2.45)%, (8.44 +/- 2.51)%, (19.87 +/- 6.13)%, while the results of platelet
      concentrates were (30.65 +/- 12.33)%, (31.46 +/- 11.86)%, (32.51 +/- 13.05)%,
      (63.55 +/- 13.27)% and (10.33 +/- 4.37)%, (11.09 +/- 6.61)%, (13.46 +/- 9.69)%,
      (24.41 +/- 10.15)%, respectively. The platelet count and pH value were also
      determined. The platelet number, pH value, percentage of CD62p staining and MCF
      of CD41 had no significant difference within 3 days of platelet storage. The
      platelet number and pH value decreased significantly (P < 0.001), while
      percentages of CD62p staining and MCF of CD41 increased significantly (P < 0.001)
      on day 5 of storage. It is concluded that the quality of plateletpheresis is
      better than platelet concentrate.

PMID- 12513750
TI  - [Modified flow cytometry assay for CD62p expression of preserved platelets].
AB  - CD62p expression was an important monitoring parameter for preserved platelets
      quality. To setup an optimized flow cytometry assay for preserved platelets based
      on the CD62p expression on platelets, the platelet samples were collected, 0.1
      mmol/L persantine and 1.1 mmol/L EDTA were added into the modified TB S used to
      replace PBS dilution; the methodological evaluation were carried out. Results
      showed that 0.1 mmol/L persantine and 1.1 mmol/L EDTA achieved to prevent
      platelets activation during the test procedure. The favorable negative or
      positive samples were prepared for check of fluorescence antibody's quality to
      ensure the validity of results. CD61 was used to identify platelets for assay and
      improve veracity of assay. The special injector was also replaced by special big
      syringe needle for blood collection to reduce in vitro artifacts, and the
      prepared sample can be steady-going for 48 hours at 4 degrees C after fixed by 1%
      paraformaldehyde. It is concluded that this flow cytometry assay for CD62p
      positive platelets is simple and efficient.

PMID- 12513751
TI  - [Detection of Rh(D) before blood transfusion and its significance].
AB  - The significance of detecting the recipient's Rh D blood type before transfusion
      and the feasibility of in-time transfusion to Rh D-negative person with the same
      ABO type blood or autologous blood were explored. For 2,168 inpatients who
      applied for transfusion for the first time in the latest five years, Rh D-antigen
      was detected a day before transfusion by test tube method with IgM anti-D serum
      provided by BASO company. The results showed that seven Rh D-negative cases were
      found among 2,168 cases and the Rh D-negative rate was 0.32%. Of these seven
      cases, two were received autologous blood, two were received Rh D-negative blood
      of the same type and the other three were not treated with transfusion. It is
      concluded that hemolytic reaction of transfusion was prevented by detecting Rh D
      blood type before transfusion, autologous transfusion may be taken if the
      patient's health-condition permits.

PMID- 12513752
TI  - [Mesenchymal stem cells and related factors].
AB  - Mesenchymal stem cells possess the ability to differentiate into osteoblasts,
      chondroblasts, lipoblasts, myoblasts and so on, which can be used in the
      formation of hematopoietic microenvironment, tissue repairing and gene therapy.
      Growth factors such as TGF-beta, IGF-I, BMP and FGF can influence on the
      differentiation of MSC and they cooperate with each other. MSCs support
      hematopoiesis by secreting cytokines including G-CSF, SCF, LIF, M-CSF, IL-6, IL
      11 and are related to some diseases. MSC would demonstrate important effect on
      gene engineering.

PMID- 12513753
TI  - [TNF-related apoptosis-inducing ligand signaling pathway and hematopoietic
      malignancies].
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the
      tumor necrosis factor (TNF) family. TRAIL induces apoptosis by activating caspase
      cascades, stimulating a loss of mitochondrial membrane potential (Delta Psim) and
      cytochrome C release in the FADD/caspase-8 dependent pathway. However, TRAIL can
      also trigger transcriptional activations of the pro-oncogene of c-fos, JNK, and
      NF-kappaB by other signaling pathways downstream of FADD/caspase-8. MAPK/ERK
      activation has a dominant protecting effect over apoptotic signaling from the
      death receptors. The functional expression of TRAIL by leukemic cells may be
      involved in tumor cells evasion of immunosurveillance. Somatic mutations of TRAIL
      R1 and TRAIL-R2 genes may play a role in the pathogenesis of some tumors. TRAIL
      can induce apoptosis on various continuous transformed cell lines and primary
      tumor cells, including several of hematopoietic origin, displaying minimal toxic
      effects on normal tissues. Because of the abilities of induction of both
      cytotoxic (apoptosis) and cytostatic (cell cycle perturbation) effects on the
      leukemic cells, TRAIL is currently considered as a potential(co) therapeutic drug
      against tumors.

PMID- 12513754
TI  - [Leucocyte removal and its clinical application].
AB  - Blood transfusion leads to leucocyte-mediated adverse reactions related to the
      transfusion of leucocytes in allogeneic blood and blood products. The leucocytes
      are also capable of transmitting virus infection. Leucocyte depletion of
      homologous blood products can effectively reduce the immunosuppressive effect as
      well as minimize the likelihood of transmitting virus. Blood component
      transfusion is generally "buffy-coat-poor", which removes about two thirds of the
      leucocytes present in whole blood. Using special filters, blood component can be
      filtrated 99.9% of the leucocytes. Leucocyte-depletion using filter should
      significantly lessen the leucocyte-mediated transfusion adverse reactions, such
      as febrile non-hemolytic transfusion reactions and graft versus host disease. At
      the same time, leucocyte filtration can decrease the risk of transmitting virus.
      Otherwise, leucocyte-depletion plays very important role in the treatment of
      cardiac surgical patients to attenuate leukocyte-mediated inflammation and organ
      reperfusion injury, the treatment of ulcerative colitis, and the treatment
      intractable diseases such as autoimmune and neurologic diseases.

PMID- 12513755
TI  - [Serum levels of erythropoietin and transferrin receptor in thalassemia of the Li
      nationality].
AB  - immunosorbent To determine serum EPO and soluble transferrin receptor (sTfR)
      level and to assess the degree of erythropoietic proliferation in patients with
      thalassemia of Li nationality, 50 cases and 50 normal individuals were studied.
      Enzyme-linked immunosorbent assay was used for EPO and sTfR. Results showed that
      serum EPO and sTfR levels in beta-thalasemia major patients were significantly
      higher than those in normal control group, and no significant difference in beta
      thalassemia minor cases with those in control. It is concluded that increase of
      serum EPO and sTfR level is related to the type of thalassemia.

PMID- 12513756
TI  - [Functional expression of Flt3 and c-kit on cord blood CD34(+) stem/progenitor
      cells and its significance].
AB  - To investigate the expression and function of the receptors of early-acting
      cytokines on cord blood CD34(+) hematopoietic stem/progenitor cells, the studies
      of Flt3 and c-kit were undertaken at the gene and protein levels. Fresh and
      cultured cord blood CD34(+) stem/progenitor cells were analyzed by flow
      cytometric two-color direct immunofluorescence methods and RT-PCR, while function
      of receptors was studied in vitro. It was found that (68.8 +/- 15.4)% of CD34(+)
      cells expressed Flt3, (50.6 +/- 12.7)% of CD34(+) cells expressed c-kit, the
      proportion of CD34(+) cells expressing Flt3 and c-kit decreased as in vitro
      culture time extended. It was concluded that cord blood CD34(+) stem/progenitor
      cells are capable of expressing Flt3 and c-kit for as long as 2 - 3 weeks in
      liquid medium, during the first week of culture, SCF and FL enhanced the
      generation of cells and progenitors notably.

PMID- 12513757
TI  - [Expression of telomerase during induction of committed differentiation of human
      cord blood hematopoietic stem/progenitor cells in vitro].
AB  - To investigate the expression of telomerase in cord blood hematopoietic
      stem/progenitor cells during their committed differentiation in vitro and provide
      an index of monitoring the proliferating potential of the hematopoietic
      stem/progenitor cells and security for clinical application. Human CD34 positive
      cells were isolated from umbilical cord blood by using magnetic cell sorting
      system (MACS), and were induced to differentiation with hematopoietic growth
      factors (SCF + IL3 + IL6 + GCSF and SCF + IL3 + IL6 + EPO) in a liquid culture
      system. The telomerase activity and the cytalytic subunit of telomerase (hTERT)
      of the cells were analysed during different periods of culture by using TRAP-PCR,
      TRAP-ELISA, Western blot and RT-PCR techniques, respectively. The results showed
      that a peak of cell growth was achieved on day 14 - 21 during induction of
      differentiation in vitro. Total cell number could increase 1006.4 +/- 103.2 times
      and could not increase there after. Telomerase activity and hTERT expression were
      low in freshly isolated cord blood CD34(+) cells and increased after about 7 days
      of culture in addition of cytokine combinations of SCF + IL3 + IL6 + GCSF and SCF
      + IL3 + IL6 + EPO, respectively. The telomerase activity and hTERT decreased
      after 14 days of culture and were not detected after 28 days of culture. It was
      concluded that the hematopoietic stem/progenitor cells can be expanded in large
      number in vitro and do not have the character of immortality and the telomerase
      activity could be a useful index in hematopoiesis regulation.

PMID- 12513758
TI  - [Mesenchymal stem cells suppress allogeneic T cell responses by secretion of TGF
      beta1].
AB  - To investigate the mechanisms underlying the issue that bone marrow mesenchymal
      stem cells (MSC) could trigger low responsiveness of allogeneic T lymphocytes
      against alloantigens, phenotypes of T cells were analysed with flow cytometry
      before and after coculture of allogeneic T lymphocytes with MSC. Further,
      expression of cytokines including IL-4, IFN-gamma and TGF-beta1 was evaluated by
      RT-PCR and ELISA as well. The results showed that CD8(+) subpopulation was
      increased and CD25(+) subset was decreased in proportion after coculture of
      allogeneic T lymphocytes with MSC for 2 weeks. RT-PCR assay showed that MSC
      expressed TGF-beta1 but not IL-4 and IFN-gamma, and the result was further proved
      by ELISA assay showing that the secretion of TGF-beta1 reached to 1 ng/ml in 72
      hours. It was concluded that allogeneic MSC suppressed T cells activation by
      alteration of T cell subpopulations. The suppressive effect was at least in part
      due to the secretion of TGF-beta1. The results indicate that MSC pretreatment
      might be useful in the prevention of GVHD in HLA-mismatched bone marrow
      transplantation and further donors for hematopoietic stem cells could be selected
      from greater potentials.

PMID- 12513759
TI  - [Inhibitory effect on proliferation of KG1a cell line by methyltransferase
      inhibitors].
AB  - To explore the possibility of a new therapeutic strategy for leukemia by
      intervening in the DNA methylation to re-express p15 suppressor gene, methylation
      inhibitors, 5-Aza-2'-deoxycytidine (5-Aza-CdR) and cell differentiation agent
      (CDAII) were used to treat myelogenous leukemia cell line KG1a in which p15 gene
      expression was suppressed due to DNA hypermethylation. The biological
      characteristics of KG1a cells untreated or treated with the agents were
      investigated and analyzed using morphology, methylation specific-PCR (MSP), (3)H
      labeled microassay technique, restriction endonuclease reaction, flow cytometry
      and immunofluorescence methods. The results indicated that both agents showed
      concentration-dependent and time-dependent inhibition of cell proliferation. 5
      Aza-CdR and CDAII induced apoptosis and cell differentiation with G(2) and
      G(0)/G(1) arrest respectively. Furthermore, DNA methyltransferase activity and
      level of methylation in genomic DNA were decreased and p15 protein was re
      expressed partially. It is concluded that it is possible to treat leukemia by
      intervening in the DNA methylation using methyltransferase inhibitors and it is
      worth to make a thorough study on mechanism of the new strategy.

PMID- 12513760
TI  - Regulative function of extracellular regulated protein kinases and telomerase in
      apoptosis of hepatocarcinomatous and leukemic cell lines.
AB  - In order to investigate the change of telomerase activity and phosphorylated
      (activated) extracellular regulated protein kinases (ERK) 1 and 2 in
      hepatocarcinomatous cell line SMMC7721 and leukemic cell line K562 proliferation
      inhibition and apoptosis, three kinds of chemotherapeutic drugs harringtonine
      (HRT), vincristine (VCR) and etoposide (VP-16) were selected as inducers; and MTT
      assay, flow cytometry analysis, telomeric repeat amplification protocol (TRAP)
      assay and bioluminescence analysis were used. The results showed that after
      treatment of HRT, VCR and VP-16 for 24 hours, the cell proliferation was
      inhibited, apoptosis was induced, and telomerase activity and the protein
      expression of phosphorylated ERK1/2 were down-regulated. In HRT treated groups,
      the descendent grade was the most obvious. It was concluded that the common
      molecular mechanism of these chemotherapeutic drugs killing SMMC7721 and K562
      cell lines might be through inhibiting ERK signal transduction pathways, cutting
      down ERK activity, reducing the transcription of target genes of ERKs, then
      indirectly down-regulate telomerase activity, and cell apoptosis is the final
      result of durative loss of telomere.

PMID- 12513761
TI  - [Study on clonal proliferation of TCR Vbeta subfamily T cells induced by AML
      M(2a) cells in vivo and in vitro].
AB  - To observe the expression and clonal expansion of TCR Vbeta subfamily T cells
      induced by AML-M(2a) cells in vivo and in vitro, complementary determining region
      3 (CDR3) of TCR beta with variable region genes was amplified by using RT-PCR in
      both peripheral blood mononuclear cells (PBMNC) and T cells from mixed lymphocyte
      and tumor culture (MLTC) from four AML-M(2a) patients. The positive products were
      further analyzed to identify the clonality of T cells by genescan. The results
      showed that the similarity distribution of TCR Vbeta subfamily T cells was found
      Vbeta in PBMNC and MLTC. One or two clonality expansions of T cells could be
      found in predominant TCR Vbeta subfamily T cells induced by A ML-M2a cells from 3
      cases in vivo and in vitro. It was concluded that clonal expansion of TCR Vbeta
      subfamily T cells stimulated selectively by AML-M(2a) cells may be a specific
      immune response of patient's T cells to AML-M(2a) cells associated antigen. The
      clonal proliferation of TCR Vbeta subfamily T cells were affected somewhat by
      environmental difference in vivo and in vitro.

PMID- 12513762
TI  - [Myelodysplastic syndrome with early presentation of refractory monolineage
      cytopenia-with report of 13 cases].
AB  - To find the relationship between myelodysplastic syndrome (MDS) and refractory
      monolineage cytopenia, thirteen cases of MDS with early presentation of
      monolineage refractory cytopenia were analyzed retrospectively. The results were
      as follows: (1) The percentage of 13 cases with refractory monolineage cytopenia
      were 5.9% of the total 219 MDS patients in the past 10 years. (2) The median time
      of patients with monlineage cytopenia to M DS diagnosed was 48.5 +/- 55.3 months.
      The median times from monolineage cytopenia to MDS diagnosed for patients with
      neutropenia, erythrocytopenia and thrombocytopenia were 12.5 +/- 9.5 months, 53.8
      +/- 54.6 months and 59.2 +/- 65.5 months, respectively. (3) The common
      characteristics of 13 cases were as follows: (a) the macrocytic erythrocytes in
      peripheral blood and the percentage of intermediate and late erythroblast in bone
      marrow were increased; (b) occasionally few cells with dysplasia could be found;
      (c) all patients with erythrocytopenia and thrombocytopenia transformed to RA and
      RAS while the most of patients with neutropenia transformed to RAEB subtype; (d)
      autoantibody could be found in part of the patients. It is concluded that some of
      refractory monolineage cytopenias in essence are the early states of MDS.

PMID- 12513763
TI  - [Change of telomerase activity in bone marrow cells from chronic myeloid leukemia
      patients in different phases].
AB  - To study the telomerase activity change in patients with CML different phases,
      telomerase PCR-ELISA method was used. Results showed that telomerase activity of
      normal bone marrow cells was low. The telomerase activity in CML at any phase was
      higher than that in normal bone marrow (P < 0.05). The telomerase activity in
      accelerated and acute transformation phases was higher than that in chronic phase
      (P < 0.05), but there was no significant difference between accelerated phase and
      acute transformation phase. It was concluded that telomerase activity could be
      used as an useful marker for evaluating development of course and curative effect
      of CML.

PMID- 12513764
TI  - [Study on angiogenesis of multiple myeloma in vitro].
AB  - Angiogenesis is a necessary step in tumor progression, and it correlates an
      unfavorable prognosis. In multiple myeloma, bone marrow microvessel density and
      angiogenesis grading correlated with plasma cell labeling index and are poor
      survival predictors, but the study of myeloma's angiogenesis is very rare. This
      article was to study the effect of multiple myeloma cell line conditioned media
      on the proliferation, migration and angiogenesis of human bone marrow endothelial
      cells (HBMEC). The multiple myeloma cell line conditioned media were obtained by
      using RPMI 1640 media containing 2% fetal bovine serum (FBS) to cultivate myeloma
      cell lines for 18 hours. Proliferation and migration of HBMEC were detected by
      using those media to cultivate HBMEC. Capillary tube formation was performed by
      using microcarriers cytodex-3 covered with HBMEC in three-dimensional fibrin
      matrices. The results showed that myeloma conditioned media induced HBMEC's
      proliferation and migration (P < 0.001), and those media induced capillary tube
      formation (length and width) of HBMEC (P < 0.001). It was concluded that myeloma
      cell lines induce HBMEC's proliferation, migration, and capillary tube formation
      by secreting several cytokines.

PMID- 12513765
TI  - [Effects of sodium orthovanadate on proliferation and apoptosis in raji cells and
      its mechanism].
AB  - In order to investigate the role and the mechanism of protein tyrosine
      phosphatase (PTPase) signaling pathway in the regulation of proliferation, cell
      cycle and apoptosis in lymphoma cells, the effects of sodium orthovanadate,
      Na(3)VO(4), a specific PTPase inhibitor, were explored on Raji lymphoblast-like
      cell line by MTT assay and CFU-Raji culture, morphologic observation, DNA gel
      electrophoresis, FCM and RT-PCR. Results showed that MTT assay and CFU-Raji
      culture demonstrated that sodium or thovanadate inhibited the growth of Raji
      cells in a concentration-dependent fashion; morphologic observations showed that
      Raji cells exhibited cytoplasm shrinkage, cytoplasm membrane blebbing, nuclear
      fragmentation and chromatin condensation forming crescents along nuclear membrane
      characteristic of apoptosis in the presence of Na(3)VO(4); DNA gel
      electrophoresis revealed typical DNA ladder reminiscent of DNA cleavage at
      internucleosomal sites in Na(3)VO(4) treated cells; FCM and RT-PCR indicated that
      Na(3)VO(4) intervention increased the fraction of annexin V(+) PI(-) cells,
      reduced the value of mitochondrial transmembrane potential, induced G(2)/M arrest
      and down-regulated the expression of Bcl-2 and cyclin B1 at both mRNA and protein
      level in a concentration-dependent manner. It was concluded that PTPase pathway
      might be implicated in the regulation of cell proliferation, cell cycle and
      apoptosis, and PTPase specific inhibitor Na(3)VO(4) could induce Raji cell growth
      inhibition, G(2)/M arrest and apoptosis via down-regulation of Bcl-2 and cyclin
      B1, and reduction of mitochondrial transmembrane potential.

PMID- 12513766
TI  - [Study on expression of cytokines mRNA induced by B7-1-transfected Raji and
      Jurkat cells].
AB  - To investigate the function of B7 co-stimulator in activation and differentiation
      of T cell, B7 gene was transfected into Raji and Jurkat cells by liposome, B7
      expression in tumor cells was detected with flow cytometry, and expression of IL
      2, IL-4 and IFN-gammamRNA was detected by RT-PCR. Kinetics of secretion of three
      cytokines was also analyzed at 4, 12, 20 and 48 hours after gene transfection.
      The results showed that B7(+) Raji cells could induce mRNA expression of IL-2, IL
      4 and IFN-gamma on T cell surface; B7(+) Jurkat cells could induce secretion of
      IL-2 and IFN-gamma. However, B7(-) Raji and B7(-) Jurkat cells could not induce
      secretion of cytokines. Kinetics of the three cytokines secretion were different,
      IL-2 and IL-4 were only detectable after 4 hours of T cell activation, whereas
      IFN-c was detectable after 12 hours of stimulation. The peak levels of IL-2, IL-4
      and IFN-gamma were found at 20 hours after activation. It was concluded that
      tumor cell lines transfected with B7 gene could enhance their immunocompetence,
      activating T cell efficiently and B7-1 play more critical role in T cell
      activation and differentiation.

PMID- 12513767
TI  - [Apoptosis of Fas(+) Yac-1 cells induced with Fas ligand-transfected COS-7
      cells].
AB  - The possibility of immunotherapy for lymphoma by single FasL-Fas way was
      investigated. After pBillneo-mFasL was transformed into competent E. coli
      DH5alpha and amplified, the plasmid DNA was prepared and purified from the
      DH5alpha. To determine the primary structure and inserting direction of mFasL
      cDNA gene in pBillneo-mFasL, the plasmid DNA was cleaved by restriction enzyme,
      and the mFasL cDNA of pBillneo-mFasL was amplified by polymerase chain reaction
      (PCR), the DNA sequence of the PCR product was analysed by automatic DNA
      sequencing. After pBillneo-mFasL was transfected into COS-7 cells by liposome,
      the COS-7 cells were selected with G418 selective medium, and the expressing
      levels of mFasL cDNA on the COS-7 cell membrane was assayed by Western Blot.
      After the COS-7 cells higher expressing mFasL protein and mouse lymphoma cell
      line Yac-1 expressing Fas were cocultured for 5 hours, the suspending Yac-1 cells
      were collected and labeled by annexin V/PI kit. The apoptosis rate of the Yac-1
      cells was tested by flow cytometry. The EcoRI cleaving products of pBillneo-mF
      asL included 920 bp and 7227 bp fragments. Its Hind III cleaving products
      included 1293 bp and 6807 bp fragments. These results showed: (1) the length of
      DNA sequence containing mFasL cDNA within pBillneo-mFasL is the same as
      theoretical length; (2) the inserting of mFasL cDNA in pBillneo-mFasL was in
      positive orientation. The expected 890 bp DNA fragments of mFasL cDNA (from ATG
      to +36 bp following TAA) emerged in PCR product with pBillneo-mFasL as a
      template. The sequencing result of the PCR product equaled the known mFasL cDNA
      sequence in the gene bank. The COS-7 cells transfected by pBillneo-mFasL and
      selected with G418 culture medium expressed more mFasL membrane protein assayed
      by Western Blot. After the COS-7 cells were cocultured with Fas(+) Yac-1 cells in
      different E:T ratios (1:1, 5:1 and 10:1) for 5 hours, the apoptosis rates of Yac
      1 cells were (22 +/- 4.8)%, (32.18 +/- 7.8)%, and (51.8 +/- 5.4)%, respectively.
      These were obviously different from the control group (P < 0.01), in which the
      COS-7 cell was transfected by pBillneo (not carrying mFasL gene). It was
      concluded that lymphoma cells highly expressing Fas can be effectively killed
      through single Fas-FasL way in vitro.

PMID- 12513768
TI  - [Sperm-mediated expression of human clotting factor VIII gene in transgenic
      offspring of mice].
AB  - The expression of human clotting factor VIII gene was observed in transgenic off
      spring of mice through artificial insemination with sperm as carriers. Female
      mice were impregnated through artificial insemination by introducing sperm
      carrying pRC/RSV-hF VIII BD, which contained human F VIII BD (B-domain deleted)
      cDNA (hF VIII BD c DNA), into the uteri. During the fourth week after the birth
      of new-born mice, PCR was used to screen hF VIII BD cDNA positive transgenic
      mice, then blood of which was collected for detecting the antigen and Anti-hF
      VIII inhibitors, simultaneously, the transcription and expression of hF VIII BD
      cDNA were investigated by Northern blot and Western blot. The results showed that
      7 became pregnant of 20 inseminated mice, and 11 new-born mice came into the
      world, out of which 9 survived at last. Three hF VIII BD cDNA-positive-transgenic
      mice had been screened out by PC R, in which the antigen of human F VIII in
      plasma was 8.65 ng/ml, 7.84 ng/ml and 8.44 ng/ml, respectively, the Anti-hF VIII
      inhibitors were all negative. Northern blot and Western blot showed that the
      transcription and expression of hF VIII BD cDNA existed in tissues such as
      spleen, liver, lung and kidney of 3 transgenic mice. It was concluded that
      transgenic mice carrying human F VIII gene can be generated by sperm-carrier
      techniques and express human F VIII protein. This experiment provides important
      data for manufacturing transgenic animal carrying human F VIII gene, which can
      work as a biological reactor to produce human F VIII protein, through sperm
      carrier techniques.

PMID- 12513769
TI  - [Plasma soluble interleukin-2 receptor level in patients with idiopathic
      thrombocytopenic purpura and its clinical significance].
AB  - To investigate contribution of soluble interleukin-2 receptor (SIL-2R) to the
      clinical progress of idiopathic thrombocytopenic purpura (ITP), SIL-2R levels
      were measured in the plasma of 34 patients and 34 normal controls with double
      antibody sandwich ELISA. The cohort consisted of 12 patients with chronic ITP, 15
      with acute ITP and 7 with ITP in remission. The results showed that the mean SIL
      2R level of chronic ITP group was significantly higher than those of both the
      control and acute ITP group (P < 0.001 and P < 0.01, respectively). The SIL-2R
      level of 7 cases in remission, however, was not significantly different from that
      of normal controls. Furthermore, the plasma levels were dramatically lowered in
      patients responsive to VLAP regimen (vincristine, L-imidazole, antaisu and
      prednisone), and those were not evidently decreased in unresponsive patients. It
      was concluded that T cell activation may play a role in the development of ITP,
      and further, the level of plasma SIL-2R might predict the prognosis of ITP.

PMID- 12513770
TI  - Allogeneic bone marrow transplantation for chronic myeloid leukemia using HLA
      identical sibling donors primed with G-CSF.
AB  - Many studies have shown that G-CSF mobilized peripheral blood progenitor cell
      transplants (PBPCT) manifests faster recovery kinetics than conventional bone
      marrow transplants. This potential advantage of PBPCT still needs to be balanced
      against the risk of acute and chronic GVHD associating with the infusion of 10 -
      15 fold higher donor lymphocyte number in unmanipulated allogeneic PBPCT than the
      marrow graft. To evaluate the effect of G-CSF primed bone marrow as a source of
      stem cells in the HLA-matched sibling transplantation, G-CSF primed with non
      primed donor marrow in engraftment and incidence of GVHD for a homogenous group
      of patients with chronic myeloid leukemia (CML) were compared. Fifty patients
      with CML underwent bone marrow transplant, thirty-two donors (study group) were
      given G-CSF 3 - 4 micro g/kg per day for seven days prior to marrow harvest and
      eighteen donors (control group) had marrow harvest without G-CSF stimulation.
      Conditioning regimen consisted of total body irradiation and cyclophosphamide
      (CY), busulfan and CY, or busulfan, total body irradiation and CY. Both groups
      received same post-grafting GVHD prophylaxis and postgrafting G-CSF treatment. It
      was found that G-CSF primed donor marrow yielded with significantly higher number
      of total nucleated cells as well as CD34(+) cells and CFU-GM compared to non-G
      CSF primed marrow (P = 0.001). The median engraftment time for absolute
      neutrophil (ANC > 0.5 x 10(9)/L) was day 15 (range 10 - 22) in the group of G-CSF
      primed vs day 21 in the non-primed donor group (P = 0.001). The median time for
      platelets (> 20 x 10(9)/L) was day 17.5 (range 13 - 28) in the group of G-CSF
      primed vs day 24 in non-primed group (P = 0.001). The incidence of acute GVHD
      grade II - IV in G-CSF primed donor group was surprisingly as low,as only two
      cases of thirty-two transplants (6.3%) with acute GVHD grade II limited to the
      skin. Whereas, five of eighteen patients (27.8%) in the control group developed
      acute GVHD grade II - IV (P = 0.032). G-CSF primed donors showed reduced CD4(+)
      and increased CD8(+) cells, resulting in a significant reduction of CD4(+)/CD8(+)
      ratio as compared with non-primed marrow. The total CD3(+) cell count kept
      unchanged in G-CSF primed donors. There were not significant differences in the
      incidence of the chronic GVHD (24% vs 33.3%), relapse rate (12.5% vs 11.1%) and
      overall survival rate (78.1% vs 66.7%, P = 0.32) during 6 - 50 months of follow
      up. In conclusion, G-CSF primed donor marrow accelerates engraftment. Although G
      CSF did not change the total CD3(+) cells in bone marrow, it altered the ratio of
      CD4(+) and CD8(+) cells and significantly reduced the incidence of acute GVHD.

PMID- 12513771
TI  - [Determination of CD34(+) cells in mobilized peripheral blood by flow cytometry].
AB  - To explore a simple and effective method to determinate the volume of CD34(+)
      cells in the peripheral blood of donors received drug mobilization for stem cell
      transplantation by using flow cytometry, the mobilized peripheral blood from
      donors and 100 micro l fresh whole blood were labeled with monoclonal antibodies
      Anti-CD34-PE and Anti-CD45-FITC, after lying the red blood cells, and assessed
      with flow cytometer FL2 (log) vs SSC (log) and FL1 (log) vs SSC (log) were mainly
      used for analysis windows. The results showed that a level of CD34(+) cells in
      whole nucleated cells as low as 0.05% - 0.1% can be detected effectively using
      this method when 10(5) nucleated cells were counted. At day 5 or day 6, the level
      of CD34(+) cells in most samples of patients reached a peak volume, some of
      samples and the levels were more than one percent in. It was concluded that
      CD34(+) cells can be effectively determined by using this method. According to
      the relative rate of CD34(+) cells, the time to harvest the stem cells in blood
      can be determined.

PMID- 12513772
TI  - [Separation and cryopreservation of cord blood mononuclear cells].
AB  - The influencing factors on cord blood storage after collection and mononuclear
      cell separation as well as cryopreservation were studied. The mononuclear cell
      are separated from blood after blood collection, then cryopreserved and washed
      after thawed. Results showed that the cord blood kept at 4 degrees C or room
      temperature less than 24 hours after blood collection, mononuclear cell separated
      by hydroxyethylstarch and 2 centrifugations, mononuclear cell cryopreserved with
      50% DMSO and autoplasma from cord blood as protectives and washing the cells
      after thawing. In conclusion, the optimal project in this study can effectively
      preserve cord blood mononuclear cells.

PMID- 12513773
TI  - [The probability of microbiological contamination during the collection and
      processing of umbilical cord blood].
AB  - To study the pathogens incidences in cord blood and the efficiency of different
      detective methods, 60 samples were drawn and reserved from collected and
      processed cord blood, respectively. The BACTEC 9050 system, improved
      Martin/thioglycollate broth (22 degrees C) and thioglycollate broth (35 degrees
      C) were employed to detected bacteria (including fungus) at the same time. Two
      hundred and six cord blood serum samples were used to detect the HBV DNA and HCV
      RNA by molecular biology technique, HBsAg, Anti-HBC, Anti-HCV, Anti-HCMV-IgM,
      HTLV-1, HTLV-2, HIV-1 and HIV-2 by ELISA and RBC agglutination test were used to
      detect the TPHA. Results showed that using BACTEC 9050 system, the incidence of
      bacteria and fungus was 3.33% and 0% respectively in collected cord blood; in
      processed cord blood, the rates increased to 6.67% and 1.67%, respectively. The
      sensitivity of BACTEC 9050 was higher than that of Martin/thioglycollate broth
      (22 degrees C/35 degrees C) culture. In 206 serum samples, the positive rate of
      HBV DNA was 5.8%, HCV RNA was 2.4%, HBsAg was 2.4%, HCMV-IgM was 1.89%, HCV was
      2.4% and Anti-HBC was 29.4%. In those samples that Anti-HBC was positive, the
      positive rate of HBV DNA was 6.7%. It was concluded that the incidences of
      microbiological contamination in cord blood were high. The routine culture system
      would lead to false negative results of obligate anaerobes. It was necessary to
      replace the current culture system with improved system, such as BACTEC 9050
      system. The molecular biology technique would make up for the default of ELISA.

PMID- 12513774
TI  - [Clinical features of hematological abnormality in systemic lupus erythematosus
      related hematological disorders].
AB  - In order to investigate the clinical characteristics of hematological abnormality
      in patients with systemic lupus erythematosus (SLE) and inquire into the basis
      for differential diagnosis, the hematological data of 92 cases with lupus
      erythematosus-related hematological disorder (SLERHD) were retrospectively
      analyzed by use of SPSS/PC software. The results showed that these patients were
      short of specificity in clinical manifestation and hemogram, however, all cases
      possessed multiple SLE-related autoantibodies, increase of serum globulin level
      and varying extent dermal and arthral signs. The incidence of primary or initial
      symptom in the 92 cases was as follow: 65 anemia (72.8%), 39 purpura (42.4%), 17
      hemolytic anemia (18.5%), 56 leukopenia (60.9%), 54 thrombocytopenia (58.7%), and
      41 pancytopenia (44.6%). The bone marrow examinations showed that the cellularity
      of nucleated cells was mostly normal, and active proliferation in 57 cases
      (61.9%) and hypercellularity in 35 cases (38.1%); the G/E ratio was normal in
      majority, and G/E ratio > 3 in 59 cases (64.1%) and < 3 in 33 cases (35.9%) and
      G/E < 1 in 17 cases with hemolytic anemia Coombs' test positive; megakaryocyte
      counts were normal in 11 cases (11.9%), increase in 80 cases (86.9%) and lower
      than 7/marrow smear in 1 case (1.1%). Neutrophil alkaline phosphatase staining
      was negative in all of the cases. From above data it is concluded that patients
      with SLERHD are varied in clinical and blood pictures, but all patients are
      provided with multiple SLE-related autoantibodies, globulinemia and dermal and
      arthral signs. It is easy to identify SLERHD from aplastic anemia,
      myelodysplastic syndrome, idiopathic thrombocytopenic purpura, autoimmune
      hemolytic anemia and Evans' syndrome by comprehensive and detailed clinical and
      laboratory examinations.

PMID- 12513775
TI  - [Abnormality of p15(INK4b) gene and myelodysplastic syndrome].
AB  - Among tumor suppressor genes, p15(INK4b) gene is gaining more attention for its
      important role in the progression of myelodyplastic syndrome (MDS). Serial
      studies demonstrated that highly frequent hypermethylation of p15(INK4b) gene,
      which is located at the 5'CpG island in the promoter region of exon 1 and is the
      main reason of inactivation of p15(INK4b) gene, occurs during the development of
      MDS towards AML. The assay of methylation-specific PCR (MSP) is sensitive to this
      pattern of methylation which is restricted to the MDS clone. Apoptosis mediated
      by cytokines such as Fas antigen and TGF-beta, and bHLH proteins is inhibited by
      the inactivation of p15(INK4b) gene. This may result in the evolution of MDS
      clone to AML. In as much as the close relationship between p15(INK4b) gene
      methylation and MDS, modulation of the methylation status of p15(INK4b) gene may
      be considered as a noval treatment modality for MDS.

PMID- 12513776
TI  - [WT1-mediated pathway of transcriptional regulation and leukemia].
AB  - WT1 gene encodes a zinc finger transcription factor that regulates transcription
      of its downstream genes. Some of target genes for WT1 are involved in regulating
      both cell cycle and cellular proliferation and differentiation. However, WT1
      itself is regulated by its upstream genes such as NF-kappaB and GATA-1. Thus
      there exists a pathway of transcriptional regulation mediated by WT1, which
      controls development of hematopoietic system. Leukemia results from disrupting
      the homeostasis among hematopoietic proliferation, differentiation and apoptosis,
      which is often the consequence of an inappropriate expression of transcription
      factors and subsequent disruption of the normal gene expression pattern. This
      article reviews the relationship between the WT1-mediated pathway of
      transcriptional regulation and leukemia.

PMID- 12513777
TI  - [Alteration of serum lipids in patients with acute leukemia and its clinical
      significance].
AB  - To explore the clinical significance on alteration of serum lipids in acute
      leukemia (AL) patients, the level of serum lipids was monitored in 86 AL cases by
      using of automatic biochemical analyzer. The results showed that TG was
      significantly higher (P < 0.05) while TC, LDL-C and HDL-C were obviously lower (P
      < 0.05) in AL patients than those in normal controls. After chemotherapy, TG
      decreased but TC, LDL-C and HDL-C were still higher (P < 0.05) as comparing to
      pre-treatment in complete remission cases. There were no changes of those
      parameters in non-remission patients. It is concluded that determination of serum
      lipids level in AL patients is a simple and important accessory index to evaluate
      curative effect and monitor patient's condition.

PMID- 12513778
TI  - [Determination of serum granulocyte colony-stimulating factor level in patients
      with chronic idiopathic neutropenia and its significance].
AB  - To investigate the serum granulocyte colony-stimulating factor (G-CSF) level in
      patients with chronic idiopathic neutropenia (CIN) and analyze its clinical
      significance. By the use of G-CSF-specific enzyme-linked immunosorbent assay
      (ELISA), the serum levels of G-CSF were determined in 40 cases with chronic CIN,
      40 cases with systemic lupus erythematosus (SLE) complicated neutropenia and 40
      healthy volunteer (normal control). Results showed that serum G-CSF was positive
      in 11 normal controls and in 10 cases with SLE, and the G-CSF levels were (27.34
      +/- 8.00) ng/L and (26.76 +/- 7.26) ng/L, respectively. Serum G-CSF in 27 cases
      with CIN was positive, the level was (134.04 +/- 89.29) ng/L, which was higher
      than that in the normal controls and the cases with SLE (P < 0.01). It was
      concluded that an obstacle to utilization of G-CSF could be existed in the
      patients with CIN.

PMID- 12513779
TI  - [Clinical report on treatment of thrombocytopenia with rhIL-11 (Mega) in 10
      chronic aplastic anemia patients].
AB  - In order to evaluated the curative effect of rhIL-11 (Mega) on thrombocytopenia
      in chronic aplastic anemia (CAA) patients, ten CAA cases with thrombocytopenia
      after administration of conventional drugs were selected and subcutaneously
      injected 0.75 mg Mega per day in 1 - 2 courses of treatment on the basis of
      conventional therapy. Results showed that platelet counts were obviously
      increased and the bleeding symptoms were alleviated in all CAA patients after
      application of Mega for treatment. In conclusion, the rhIL-11 (Mega) could be
      used as an effective drug for treatment of thrombocytopenia in CAA patients.

PMID- 12513780
TI  - [Screening of differentially expressed genes in the mouse hematopoietic stromal
      cells after long-term culture].
AB  - Hematopoietic stromal cells, being the essential ingredient of the hematopoietic
      microenvironment, play very important roles in the control and regulation of self
      renewal, proliferation and differentiation of hematopoietic stem cells (HSC) via
      complex interactions of cell-cell, cell-humoral and cell-extracellular matrix.
      Evidence from in vivo experiment has proved that HSC derived from normal mice
      could reconstitute hematopoiesis of mice with HSC defects but failed to
      reconstitute hematopoiesis of those mice with microenvironment defects, showing
      the importance of hematopoietic microenvironment in the maintenance of
      hematopoiesis in vivo. A well-known long-term culture (LTC) system established by
      Dexter demonstrated in another way that stromal cell layer in the system could
      support ex vivo hematopoiesis for several months, even more than one year under
      the optimal conditions. It, however, has not been demonstrated that what is the
      key elements and in which way the ex vivo hematopoiesis could be maintained for
      so long time. As the inventions for the large-scale screening methodologies the
      suppression subtractive hybridization (SSH) was chosen for the screening
      differentially expressed genes expressed by LTC cultured stromal cells but not by
      the uncultured bone marrow cells (BMC). mRNA extracted from both cultured
      adherent cells (tester) and BMC (driver) were hybridized according to the
      protocol provided by CLONTECH. Total of 130 clones differentially expressed by
      cultured cells were randomly picked up and 106 ESTs were obtained after
      sequencing. They represent 26 identical or similar genes and 7 novel genes after
      the bioinformatics analysis. 5 of the novel genes with the entire open reading
      frame, without functional clues, have been cloned into the mammalian expression
      vectors and the functions of them in the control of proliferation and
      differentiation of HSC will be further exploring. The most interesting discovery
      is that 3 novel genes have signal peptides, implying the potential discovery of
      novel growth factors as 80% known growth factors have signal peptides. Our
      experimental results suggest that: (a) based on the results of subtractive
      efficiency, the SSH could be a reliable method to screen differentially expressed
      genes; (b) gene expression may be regulated by multiple factors, even
      conditioning-dependent, in this experiment the genes expressed by bone marrow
      stromal cells are LTC-cultivation inducible; (c) it is possible to find
      interesting genes or special gene after relatively large-scale screen.

PMID- 12513781
TI  - [Study on expression and function of fas ligand in human myeloid leukemia cells].
AB  - To determine whether the Fas receptor-Fas ligand (FasR-FasL) system, which
      triggers apoptosis in sensitive cells, is an important mechanism of cytotoxicity
      in myeloid leukemia. FasL expression was investigated in myeloid leukemia cells
      and its upregulation by a combination of IL-2 and INF-gamma, +/- as well as its
      function of inducing Jurkat cells to apoptosis mainly by flow cytometry (FCM).
      Results showed that leukemia cells expressed more FasL (3.59 +/- 1.05)% than that
      expressed in the healthy individuals (0.36% +/- 0.16)%, P < 0.001 and the FasL
      was upregulated (7.78 +/- 3.40)%, P < 0.01 when treated with IL-2 and IFN-gamma.
      Leukemia cells were co-cultivated with Jurkat cells for 24 hours. Then Jurkat
      cells were labeled with FITC-annexin V and PE-CD3 to assess apoptosis by FCM. The
      leukemia cells, which had been incubated with IL-2 and IFN-gamma, induced more
      Jurkat cells to apoptosis than the ones that freshly isolated from the peripheral
      blood mononuclear cells, which raised the figure from (8.28 +/- 1.61)% to (10.73
      +/- 2.16%). And the supernatant derived from the former killed more Jurkat cells
      than the latter. It was concluded that human myeloid leukemia cells expressed
      high levels of functional FasL that can kill Jurkat T-cells by apoptosis. FasR
      FasL sys tem could play a role in the "immune escape" and relapse of the
      leukemia. The induction of apoptosis through the Fas pathway might be a novel and
      effective approach for leukemia immunotherapy.

PMID- 12513782
TI  - [Expression of CD56 in acute leukemia and its clinical significance].
AB  - In order to investigate the expression of CD56 on acute leukemia cells and its
      clinical significance, samples from 70 patients with acute leukemia were analyzed
      with multicolor flow cytometry to determine the CD56 and other leukocyte
      differentiation antigens. The results showed that 16 of 70 cases (22.86%) were
      identified to express CD56, of which 1/35 (2.86%) patient with acute lymphocytic
      leukemia (ALL) and 15/31 (48.39%) with acute myelocytic leukemia (AML) were CD56
      positive. The positive rate of CD56 in AML was significantly higher than that in
      ALL (P < 0.01). The expression of CD56 varied in AML subtypes. The positive rate
      (11/15) of CD56 in AML-M(0), -M(1) and -M(2) was significantly higher than that
      in AML-M(3), -M(4) and -M(5) (4/16) (P = 0.013). 13 of 15 AML with CD56
      expression were also positive for HLA-DR (41.94%), and a significant positive
      correlation was found between the expression of CD56 and HLA-DR (r = 0.439, P =
      0.014). It was concluded that CD56 mainly expressed in AML cells. The analysis of
      CD56 expression on acute leukemia is of great value in the diagnosis, prognosis
      prediction and monitoring of minimal residual disease in AML patients.

PMID- 12513783
TI  - [A quantitative assay for telomerase activity in peripheral blood mononuclear
      cells from patients with acute leukemia].
AB  - To establish a quantitative assay for telomerase activity and analyze the
      telomerase activity in peripheral blood mononuclear cells (PBMNC) from patients
      with acute leukemia, a fluorescent dye, PicoGreen, was added to the products
      after telomere repeat amplification protocol. The samples were excited at 480 nm
      and the fluorescence emission intensity was measured at 520 nm using a
      spectrofluorometer. Telomerase activity was detected in PBMNCs from 20 cases of
      normal individuals and 25 patients with acute leukemia. The results showed that
      the fluorescence of PicoGreen binding to double-stranded DNA specifically was
      enhanced with increase of DNA quantities. In conclusion, the met hod is rapid,
      simple and quantitative, the telomerase activities of PBMNCs from acute leukemia
      patients are significantly higher than that of the normal controls.

PMID- 12513784
TI  - [The comparison between the mechanisms of sodium selenite induced apoptosis and
      arsenic trioxide induced apoptosis in human acute promyelocytic leukemia cell
      line NB4 cells].
AB  - In order to explore the differences between the mechanisms of selenite-induced
      apoptosis and arsenic induced apoptosis in NB4 cells, growth inhibition was
      determined by MTT test, apoptosis determined by DNA electrophoresis and analysis
      of intracellular DNA contents, reactive oxygen species and reduced glutathione in
      the cell were measured by Lucigenin dependent chemoluminescent (CL) test and
      spectrophotometry, and mitochondrial transmembrane potential was measured by flow
      cytometry. The results showed that: 5 micro mol/L sodium selenite similar to 1
      micro mol/L arsenic trioxide could induce the apoptosis of NB4 cells after
      treatment for 24 hours. Both could elevate the level of reactive oxygen species
      and intensify mitochondrial transmembrane potential collapse, accompanied with
      decrease of reduced glutathione centent. The effect of selenium selenite on these
      aspects was more significant than those of arsenic trioxide. Elevation of
      intracellular glutathione in N-acytlcysteine pretreated NB4 cells could enhance
      the selenite induced apoptosis and oxidative stress, but ameliorate the arsenic
      trioxide induced apoptosis and oxidative stress. It was concluded that sodium
      selenite and arsenic trioxide can induce the apoptosis of NB4 cells, but there
      are significant differences between the mechanisms of selenite-induced and
      arsenic-induced apoptosis in NB4 cells, particularly in the influence of
      intracellular glutathione content on the drug action.

PMID- 12513785
TI  - [Cytokine-induced killer cells induce apoptosis of K562 cells expressed bcr-abl].
AB  - In order to investigate whether cytokine-induced killer (CIK) cells can induce
      apoptosis of bcr-abl(+) K562 cells, apoptosis of K562 cells and CEM cells induced
      by CIK cells, etoposide or camptothecin was detected with flow cytometry DNA
      assay. RT-PCR showed that K562 cells expressed the bcr-abl fusion gene, K 562
      cells, K562 cells/etoposide or K562 cells/camptothecin groups showed no sub-G(1)
      peak. K562 cells/CIK cells group showed sub-G(1) peak (38.1%). CEM cells showed
      no sub-G(1) peak. CEM cells/camptothecin or CEM cells/etoposide groups showed sub
      G(1) peak (23.5% or 32.3% respectively). CEM cells/CIK cells group showed sub
      G(1) peak (45.4%). Etoposide or camptothecin did not induce apoptosis of K562
      cells. CIK cells induce apoptosis of K562 cells. Bcr-abl fusion gene prevented
      apoptosis induced by etoposide or camptothecin, but did not prevent apoptosis
      induced by CIK cells. This property may support the observed adoptive immunologic
      effect of allogeneic bone marrow transplantation and donor lymphocyte
      transfusions of CML case relapsing after allogeneic bone marrow transplantation.

PMID- 12513786
TI  - Aldehyde-dehydrogenase gene-transduced hematopoietic cell line K562 overcomes the
      cytoxicity of cyclophosphamide in vitro.
AB  - The identification of genes inducing resistance to anticancer chemotherapeutic
      agents and their introduction into hematopoietic cells represents a promising
      approach to overcome bone marrow toxicity, the limiting factor for most high-dose
      chemotherapy regimens. Because resistance to cyclophosphamide has been correlated
      with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in
      tumor cells lines in vitro, this study tested whether ALDH1 overexpression could
      directly induce cyclophosphamide resistance. Results showed that a retroviral
      vector was used to transduce full-length human ALDH1 cDNA into human
      hematopoietic cell line K562 that was then tested for resistance to 4
      hydroxycyclophosphamide (4-HC), an active analogue of cyclophosphamide.
      Overexpression of the ALDH1 gene resulted in a significant increases in
      cyclophosphamide resistance in transduced K562 cells (50% inhibition
      concentration, IC50 = 10 micro mol/L). These findings indicate that ALDH1
      overexpression is sufficient to induce cyclophosphamide resistance in vitro and
      provide a basis for testing the efficacy of ALDH1 gene transduction to protect
      bone marrow cells from high-dose cyclophosphamide in vivo.

PMID- 12513787
TI  - [Expression of d-amino acid oxidase gene and green fluorescence protein gene
      transferred into k562e cells by retroviral vector containing internal ribosome
      entry site sequence].
AB  - The internal ribosome entry site (IRES) sequence was derived from
      encephalomyocarditis virus. It allows to translate two open reading frames at one
      mRNA, so two genes conjoined by IRES have the same expression rate. K(DfGC) and
      K(DfGd) cell lines, stably expressing D-amino acid oxidase (DAAO) gene and green
      fluorescence protein (GFP) genes, were obtained by transfection of K562e cells
      with retroviral vector pLDfG containing IRES sequence, DAAO cDNA and GFP gene.
      Fluorescence positive rate and fluorescence intensity of the two cell lines were
      measured with flow cytometry. H(2)O(2) production by K(DfGC) and K(DfGd) cells
      treated with D-alanine was measured by the phenol red oxidation assay. The
      fluorescence positive rate and fluorescence intensity in K(DfGC) and K(DfGd) cell
      were 94.64% and 96.31% and 202 units and 174 units per 2 x 10(4) cells,
      respectively. There was exponential correlation between fluorescence intensity
      and H(2)O(2) level. The above-mentioned results demonstrate that DAAO gene and
      GFP gene were simultaneously expressed in K562e cell line by the regulation of
      IRES sequence, and DAAO level was correlated with fluorescence intensity of GFP.

PMID- 12513788
TI  - [Construction of adeno-associated virus vector carried mutated dihydrofolate
      reductase and green fluorescent protein and its expression in NIH3T3 cells].
AB  - The aim of this study was to construct recombinant mDHFR-GFP/AAV vector
      containing mutated dihydrofolate reductase (mDHFR) and green fluorescent protein
      (GFP) fusion genes and its expression in NIH3T3 cells, to investigate the
      resistance of the cells to methotrexate. Amplified cDNA of mDHFR and GFP
      segmented from their plasmid separately were linked by PCR with the aminoacetic
      acid linker. The fusion gene was inserted into T vector, and after enzyme cutting
      the fusion gene fragment was inserted into AAV vector, then packaging the vector
      into recombined AAV and infected NIH3T3 cells. Expression of gene fusion was
      observed by PCR, fluorescent microscopy and flow cytometry. mDHFR and GFP cDNA
      were found in NIH3T3 genomic DNA, the GFP expression rate was about 25%, and
      resistance of the transferred cells to MTX was increased markedly. The results
      showed that AAV vector can transfer mDHFR and GFP fusion gene into NIH3T3 cells
      and increase resistance to MTX in gene modified cells. This data provided a basis
      for application of mDHFR and AAV vector in gene therapy.

PMID- 12513789
TI  - [Biological characterization of mouse erythroblastic leukemia cells in haploiden
      tical mice].
AB  - Using transplantable erythroblastic leukemia cells of EL9611(H-2d), the cells
      were inoculated to CB6F(1)(H-2d/b) generation of BALB/c x C57BL/6 mouse, the
      biological characterization of erythroblastic leukemia in haploidentical mouse
      was studied, that provides an experimental model for the study of graft-versus
      leukemia (GVL) with bone marrow or stem cell transplantation. When 10(3) - 10(8)
      of the spleen cells of EL9611(H-2d) had been intravenously inoculated to CB6F(1)
      mouse, the erythroblastic leukemia cells were transplanted successively and the
      F(1) generation of erythroblastic leukemia model in mice was established with
      100% incidence of erythroblastic leukemia. There was a linear relationship
      between the survival time and the number of leukemic cell. The survival time of
      the mice was (9.6 +/- 0.8) days when 10(6) cells were inoculated. If the CB6F(1)
      mouse was transplanted successively for four generations, the incidence was 100%.
      The main targets for the leukemic EL9611(H-2d) cells were liver, spleen and
      marrow. The reaction of the erythroblastic leukemia cells for hemoglobin staining
      was positive, while the peroxidase reaction was negative. These cells were
      sensitive to some chemotherapeutic drugs, such as cytosine arabinoside and
      cyclophosphamide. This study presents the convenience for the studies on the GVL
      with haplo-allogeneic transplantation, in the F(1) generation of erythroblastic
      leukemia model of the commonly-used CD57BL/6 x BALB/c mouse.

PMID- 12513790
TI  - [Comparative study on activated immunocytes of human bone marrow and peripheral
      blood by cytokines].
AB  - To study immunophenotype and cytotoxicity of the immunocytes in bone marrow and
      peripheral blood after activation by combined cytokines, mononuclear cells (MNC)
      of bone marrow and peripheral blood were activated by IFN-gamma, IL-1, IL-2 and
      McAb-CD3 in vitro. The cell amount and morphology during culture were observed.
      Cytochemical staining and immunophenotype analysis were done before and after
      culture in two groups of MNC. Cytotoxicity was tested by MTT method. The results
      showed that the cell number of two groups increased obviously in culture (P <
      0.05), while the peripheral blood mononuclear cells increased more markedly (P <
      0.05). The cytochemical staining showed POX decrease, but PAS increase in two
      groups. The positive ratios of CD3(+), CD56(+) and CD38(+) cells in two groups
      increased obviously after culture (P < 0.05), but there was no significant
      difference between those two groups. CD3(+) CD56(+) cells increased obviously in
      peripheral blood mononuclear cells activated by cytokines (P < 0.05), but CD3(+)
      CD56(+) cells did not increase in bone marrow mononuclear cells. There was no
      significant difference between two groups' cytotoxicity. It was concluded that
      IFN-gamma, IL-1, IL-2 and McAb-C D3 increased cell number and cytotoxicity of
      both bone marrow and peripheral blood mononuclear cells that can be used in cell
      immunotherapy.

PMID- 12513791
TI  - [Immunophenotypic characteristics of multiple myeloma cells].
AB  - To investigate the immunophenotypic characteristics of multiple myeloma (MM)
      cells, 20 bone marrow samples from patients with multiple myeloma were analyzed
      by flow cytometry with three-color direct immunofluorescence staining. Results
      showed that all of myeloma cells expressed bright CD38, dim or negative CD45 and
      negative CD19. Most of the cells were CD56(+) and a small portions were ckappa(+)
      or clambda(+), or CD20(+). The phenotypes of normal plasmocyte, CD19(+) and CD56(
      ), except CD56(-) in one-third samples, were not appeared in all detected
      samples. It was concluded that the surface marker analysis of myeloma cells is a
      useful tool for diagnosis and further evaluating prognosis of multiple myeloma.

PMID- 12513792
TI  - [Study on induction of dendritic cells from myeloid leukemia cell lines and their
      antitumor immune function].
AB  - Dendritic cell (DC) plays a key role in antitumor immune response. However, there
      is a deficiency of DC function in the majority of leukemia patients. It is a
      novel idea that expanding DC in vitro and enhancing their antitumor immune
      function and DC-based tumor vaccines may be used as an efficient immune therapy
      for leukemia. In the project, the condition to induce DC from myeloid leukemia
      cell lines and its anti-leukemia response were investigated. HL-60, K562 and THP
      1 cells were cultured with various combinations of cytokines for inducing DC. The
      morphologic features were analyzed with optical and electron microscopy. The
      phenotype of DC was detected by FCM with CD1a, CD40, CD80, CD86, HLA-A, B, C and
      HLA-DR monoclonal antibodies. The ability of DC stimulating lymphocyte
      proliferation was observed by allo-mixed lymphocyte reaction using (3)H-TdR
      incorporation. Cytotoxicity assay was measured by (51)Cr-release method. The
      level of IL-12 and IFN-gamma in supernatant of DC culture was measured by ELISA.
      It was proved that the DCs derived from K562, HL-60 and THP-1 cells showed a
      typical morphology of dendritic cell. The induced cells expressed the surface
      differentiation antigens of DC. A high expression of phenotypes was found in HL
      60-DC and THP-1-DC stimulated by GM-CSF + IL-4 + TNF-gamma and K562-DC with GM
      CSF + IL-4 + IL-12. The DCs from the 3 leukemia cell lines stimulated allo-MLR
      and CTL reaction strongly. Different contents of IL-12 were detected in the
      supernatants of DC culture and IFN-gamma in the coculture of DC and blood
      mononuclear cells. It is concluded that the myeloid leukemia cells are able to be
      induced DCs by cytokines in vitro. The different leukemia cells need different
      cytokines and cultural conditions. DCs derived from leukemia cells express
      phenotype of antigen-presenting cells. They have the ability of stimulating T
      lymphocyte proliferation and inducing CTL reaction to clear leukemia cells, and
      the DCs secrete IL-12 and increase secretion of IFN-gamma by T cells.

PMID- 12513793
TI  - [Dendritic cells cultured with human umbilical cord serum instead of fetal calf
      serum].
AB  - To investigate whether the dendritic cells (DC) could grow up in cultural system
      with umbilical cord serum (UCS), the UCS was used in the culture instead of fetal
      calf serum. The phenotype of dendritic cells was detected by flow cytometry and
      the antigen presenting ability of DC in allo-MLR was measured by MTT assay. The
      results showed that DC grown in UCS (UCS-DC) had higher expression rate of CD86,
      CD83 and HLA-DR than that in grown in FCS (FCS-DC). (P < 0.05), and their
      expression of CD1a was lower than that of FCS-DC. The ability to induce T cell
      proliferation had no difference between UCS-DC and FCS-DC. It is suggested that
      dendritic cells with more mature phenotype had been produced in the medium
      containing UCS than those in the medium containing FCS, and UCS-DC possessed
      potent ability to stimulate proliferation of allogeneic T cells.

PMID- 12513794
TI  - [Change of adhesion molecule expression on CD34(+) cells from bone marrow and
      peripheral blood during mobilization with combination of chemotherapy and G-CSF].
AB  - To explore the dynamic change of CD34(+) cell expressing adhesion molecules in
      bone marrow and peripheral blood during mobilization with combination of
      chemotherapy and G-CSF and its clinical significance, mononuclear cells of bone
      marrow and peripheral blood from malignant hematopathy cases before and after
      mobilization with G-CSF were labeled by CD45-CY-Chrome, PE conjugated anti-CD34,
      and FITC conjugated anti-CD44, anti-CD49d, anti-CD62L and anti-CXCR4. For three
      color fluorescence analysis by flow cytometry was performed on a FACScalibur.
      Also the relationship between the number of subpopulations in different
      expressions of adhesion molecules infused and the time of recovery in different
      blood cells after transplantation was evaluated. Results showed that a
      significantly lower expression of CD44(+) and CD49d(+) on CD34(+) cells in bone
      marrow after mobilization compared to that before mobilization, whereas great
      higher expression of CD44(+), CD49d(+), anti-CD62L(+) and lower of anti-CXCR4(+)
      in peripheral blood were observed after mobilization. No significant relations
      were found between expression of different adhesion molecules on CD34(+) cells
      infused and the time of reconstitution in blood cells after transplantation. It
      was concluded that this mobilizing regimen could downregulate the expressions of
      CD44, CD49d, CD62L, and anti-CXCR4 on CD34(+) cells in bone marrow, it may
      related to mobilization of CD34(+) cells from marrow to blood, and homing of
      blood CD34(+) cells into marrow.

PMID- 12513795
TI  - Double chimerism in recipient by transplantation of two allogeneic MHC-mismatched
      mouse fetal blood units.
AB  - We have constituted a mouse model for fetal blood transplantation (FBT) to cross
      over major histocompatibility complex (MHC) without causing serious GVHD. It
      seems that full matching at the MHC appears not necessary for FBT, while the
      nucleated cell dose is critical. Two fetal blood units were combined from
      different donors to increase the stem/progenitor cell dose so as to explore the
      possibility of MHC-mismatched allogeneic transplantation. 26 out of 40 mice in
      mixed FBT group survived in the observation period of 60 days after
      transplantation without obvious GVHD. Double chimerism was demonstrated by PCR
      and flow cytometric analysis; and skin transplantation test proved the induction
      of donor specific immune tolerance. Our data suggest that two MHC-mismatched
      allogeneic donor fetal blood units could simultaneously engraft and reconstitute
      immune and hematopoietic system in a mouse model. The result may be beneficial
      for the expansion of cord blood application and enables more patients to share
      the advantages of cord blood transplantation.

PMID- 12513796
TI  - [Sal I, Nru I and Mse I restriction fragment length polymorphisms of factor IX
      gene in Chinese Han people].
AB  - The purpose of this study is to investigate the Sal I, Nru I and Mse I
      restriction fragment length polymorphisms (RFLPs) of factor IX gene in Chinese
      Han people. The frequencies of FIX-192 and FIX-793 for A and G, and FIX-698 for T
      and C were analyzed by polymerase chain reaction (PCR) in unrelated normal
      Chinese Han people. A sample of 214, 210 and 206 unrelated X chromosomes were
      analyzed for FIX-192 and FIX-793 and FIX-698, respectively. The results showed
      that the frequencies for FIX-192 were 0.878 for A and 0.122 for G, with a
      heterozygosity rate of 0.213, and the frequencies for FIX-793 were 0.552 for A
      and 0.448 for G, with a heterozygosity rate of 0.494, the frequencies for FIX-698
      were 0.311 for T and 0.689 for C, with a heterozygosity rate of 0.429. It was
      concluded that the SalIand NruI and MseI RFLPs of FIX gene may be useful markers
      for carrier detection and prenatal diagnosis in Chinese families with hemophilia
      B patients.

PMID- 12513797
TI  - [Treatment of chronic idiopathic thrombocytopenic purpura with small dose
      heparin: a report of 12 cases].
AB  - In order to determine the curative effect of small dose heparin for treatment of
      chronic idiopathic thrombocytopenic purpura (CITP), a total of 12 CITP patients,
      who were failed with prednisone and immunosuppressants over 6 months, had been
      treated with subcutaneous injection of small dose heparin. The curative effects
      were seen in 8 patients and there were no exacerbation of hemorrhage during the
      therapy. The results showed that it is effective and safe to use this treatment
      for CITP.

PMID- 12513798
TI  - [CD62p expression in platelet during the preparation course of Cryopreservated
      platelet-rich plasma].
AB  - In order to explore the factors that affect CD62p expression in platelet during
      the whole course of cryopreservated platelets preparation, CD62p expression of
      platelet was evaluated by flow cytometry assay. The whole course of
      cryopreservated platelets preparation in order included whole blood collection,
      centrifugation for fresh platelet-rich plasma preparation, addition of dimethyl
      sulfoxide, and freeze in -80 degrees C refrigerator and thaw in 38 degrees C
      water bath. Result showed that the CD62p expressed slowly from whole blood
      collection to addition of dimethyl sulfoxide, but expressed abruptly after freeze
      and thaw and it occupied 82 per cent of the whole expression. It was concluded
      that the whole blood collection, centrifugation for fresh platelet enriched
      plasma preparation and addition of dimethyl sulfoxide were optimized in the whole
      course, but the damage to platelets in the whole course of cryopreservation could
      not be avoided. It suggests that improved techniques are needed to reduce the
      damage to cryopreservated platelets.

PMID- 12513799
TI  - [Statistical analysis of 4000 umbilical cord blood units preserved in shandong
      cord blood bank].
AB  - The current study analyzed the data of 4 000 umbilical cord blood (UCB) units
      collected in Shandong Cord Blood Bank from the end of 1999 to March 2001. The
      averages of nucleated cells and CD34(+) cells were more than 1.2 x 10(9) and 3.9
      x 10(6) per UCB unit respectively, and more than 1.5 x 10(9) nucleated cells per
      UCB unit were obtained in 768 UCB units. These UCB units are suitable for
      transplantation in patients with a body weight greater than 40 kg. The analysis
      of HLA gene frequency showed that A2, A24, A11, B13, B51, DR15, DR7 and DR9 are
      the common halotypes in Shandong population and similar to those in the other
      areas of China. 40% patients could search out at least 1 UCB unit with 1
      mismatched HLA locus in Shandong Cord Blood Bank.

PMID- 12513800
TI  - [Cryobiological characteristics of placental cord blood preserved in bioarchive
      auto-preserved liquid nitrogen system].
AB  - The aim of this study was to investigate the cryobiological characteristics of
      placental cord blood (PCB) cryopereserved by using BioArchive auto-preserved
      liquid nitrogen system (BioArchive system). After Hespan depletion of red blood
      cells, 5 ml mixture of DMSO and 10% Dextran 40 were added into 20 ml of enriched
      leukocyte. 53 PCB units were cryopreserved as following protocol: pre-freeze rate
      10 degrees C/min, start freeze temperature -3 degrees C, end freeze temperature 
      10 degrees C to -15 degrees C, post freeze rate 2 degrees C/min, and end
      temperature -50 degrees C. After rapid thawing at 38 degrees C, the PCB were
      washed with 5% human serum albumin -10% Dextran 40 and centrifuged at 400 x g, 10
      degrees C for 20 minutes. The results showed that the viability of nucleated
      cells post-thaw was (73.3 +/- 12.5)%, the CD34(+) cell content was (0.3 +/-
      0.21)% for pre-freeze PCB and (0.45 +/- 0.36)% for post-t haw PCB. No significant
      difference for CFU-GM/-G/-GEMM counts was found between pre-freeze and post-thaw
      PCB. Thawed PCB contained in two compartments (20 ml and 5 ml) of a freezing bag
      showed similar viability and clonogenic capacity. Differential count of white
      blood cell was significantly changed. For post-thaw PCB, it was dramatically
      decreased for the percentage of granulocytes, and highly increased for the
      percentage of lymphocytes and monocytes. It was concluded that the condition for
      cryopreservation and thawing of PCB may be harmful to mature cells, and cells
      with large size, such as granulocyte, but suitable to lymphocyte and monocyte,
      especially for the cells with small size, such as CD34(+) cells.

PMID- 12513801
TI  - [CD28/B7 costimulating signal and its clinical significance].
AB  - It is necessary that the two signals are required in T cells activation. The
      first signal is specific, which T cell receptor could recognize and bind MHC
      molecule by antigen-presenting cells. Another one is nonspecific, which results
      from CD28/B7/CTLA4 molecules on T cells and antigen-presenting cells. The both of
      signals regulate function of T cells such as the activation, proliferation and
      secreting cytokines. CTLA4 showed the up-regulation in CD28/B7 costimulatory
      pathway as a negative signal. The immunosuppression could occur by blocking
      CD28/B7 pathway. It provided useful method for immunotherapy in the autoimmune
      diseases and graft-versus-host disease. But then, the activation of CD28/B7 could
      be valuable for the immune system recognizing and eliminating tumor cells.

PMID- 12513802
TI  - [The application of molecular biology techniques in HLA-typing].
AB  - Human leukocyte antigen (HLA) is an important immunogenetic system. It plays a
      key role in immunoresponsiveness and hematopoietic stem cell and organ
      transplantation. The development of modern medicine and tissue typing promotes
      the combination of molecular biology techniques with HLA typing, and improves the
      accuracy and practicability of HLA typing. In this review, recent advances were
      concisely introduced in research of HLA typing on the application of restriction
      fragment length polymorphism (RFLP), sequence specific oligonucleotide probe
      (SSOP), single strand conformational polymorphism (SSCP), sequence specific
      primer (SSP), flow cytometry, gene chip, sequencing based typing, virtual DNA
      analysis and so on.

PMID- 12513803
TI  - [Recent advance on blood group antigen modification of porcine erythrocytes].
AB  - Advances in the field of xenotransplantation raise the intriguing possibility of
      using porcine red blood cells (pRBCs) as an alternative source for blood
      transfusion. Serologically, pRBCs share a number of characteristics with human
      red blood cells (RBCs), so pRBCs are considered the most likely donor for
      xenotransfusion. However, xenoantigens on porcine erythrocytes play major roles
      in antibody-mediated RBC destruction. Although the alphaGal epitope (Galalpha1,
      3Galbeta1, 4GalNAc-R) is the major xenoantigen on porcine erythrocytes and is
      responsible for the binding of the majority of human natural antibodies, other
      non-alphaGal xenoantigens have been identified. The importance of these non
      alphaGal xenoantigens in binding human natural antibodies and subsequently
      triggering immunological responses cannot be underestimated.

PMID- 12513804
TI  - [Construction of fetal mesenchymal stem cell cDNA subtractive library].
AB  - To identify differentially expressed genes between fetal mesenchymal stem cell
      (MSC) and adult MSC, especially specified genes expressed in fetal MSC, a cDNA
      subtractive library of fetal MSC was constructed using suppression subtractive
      hybridization (SSH) technique. At first, total RNA was isolated from fetal and
      adult MSC. Using SMART PCR synthesis method, single-strand and double-strand
      cDNAs were synthesized. After Rsa I digestion, fetal MSC cDNAs were divided into
      two groups and ligated to adaptor 1 and adaptor 2 respectively. Results showed
      that the amplified library contains 890 clones. Analysis of 890 clones with PCR
      demonstrated that 768 clones were positive. The positive rate is 86.3%. The size
      of inserted fragments in these positive clones was between 0.2 - 1 kb, with an
      average of 400 - 600 bp. CONCLUSION: SSH is a convenient and effective method for
      screening differentially expressed genes. The constructed cDNA subtractive
      library of fetal MSC cDNA lays solid foundation for screening and cloning new and
      specific function related genes of fetal MSC.

PMID- 12513805
TI  - [Stem cell factor enhances the adhesion of hematopoietic cells to fibronectin].
AB  - Adhesion to extracellular matrix plays important roles in the regulation of
      survival, proliferation, differentiation and homing of hematopoietic cells and is
      regulated by a wide variety of growth factors, adhesion receptors and other
      ligands that mediate the cell to matrix and cell to cell interaction. Stem cell
      factor (SCF) plays important roles in the regulating growth and self-renewal of
      hematopoietic stem/progenitor cells. In the report, the effects of stem cell
      factor on the adhesion of hematopoietic cells to fibronectin were observed by
      using a hematopoietic growth factor dependent cell line-Mo7e. Results showed that
      Mo7e cells express the very late antigen VLA-4 (beta1 alpha4) and VLA-5 (beta1
      alpha5) integrins. The expression of the SCF receptor (c-kit) was also detected
      in the Mo7e cells. SCF enhances the adhesion of Mo7e cells to fibronectin in a
      concentration dependent manner. SCF enhanced adhesion of Mo7e cells to
      fibronectin was blocked by anti-beta1, alpha4 and alpha5 antibodies. Addition of
      PI-3 kinase inhibitors also blocked the adhesion of Mo7e cells to fibronectin
      induced by SCF. It was concluded that SCF enhances the adhesion of Mo7e cells to
      fibronectin, and this process is mediated by integrins and PI-3 kinase pathway.

PMID- 12513806
TI  - [Retroviral vector-mediated in vitro expression of human soluble fas].
AB  - Leukemic cells from patients expressed high level FasL cause apoptosis of
      autologous activated T cells via the Fas/FasL pathway. To investigate the role of
      soluble Fas (sFas) in reversing this process, a retroviral-mediated expression
      vector pLXIN-sFas was established. A retroviral-mediated expression system of
      human sFas was established in vitro and the biological activity of the expression
      product sFas was observed. To obtain the soluble Fas cDNA, the specific part of
      the full-length Fas cDNA was deleted by multiple PCR. After pLXIN-sFas packaged
      by PA317 cells, it was transferred into the target cell COS-7. The quantity of
      the sFas was (2.2 +/- 0.7) micro g/ml in supernatant of cultured COS-7 cells, and
      it could greatly inhibit apoptosis of Jurket cells induced by anti-Fas antibody.
      Our results suggested that the recombinant is able to express the target proteins
      in vitro and it has the perfect biological activity.

PMID- 12513807
TI  - Sequence analysis of 5'-flanking region of human pax-5 gene exon 1B.
AB  - Pax-5 gene is important transcription factor in B-lymphopoiesis and B-cell
      development. To understand the regulatory mechanism of pax-5 expression, the
      immediate 5'-flanking region (6 671 bp) of human pax-gene exon 1B was isolated
      and characterized. Analysis of the total sequence showed that the proximal
      promoter includes 3 CAT boxes, 1 SP1 and 1 E box. However, there was no consensus
      sequence for a TATA box in the 5'-flanking region. Putative regulatory sites of
      further upstream in the sequence revealed 6 LMO(2)COM, 5 NFAT, 2 LPOLYA-B, 3
      GATA1, 2 AP4, 10 MZF1, 1 ETS1-B, 1 GATA3, 1 NKX25, 2 RORA1, 1 LYF1, 2 Ikaros2, 2
      TCF11, 1 GATA-C and 1 FREAC7. Therefore, the 5'-flanking region of human pax-5
      exon 1B could be involved in regulating the expression of human pax-5 and B-cell
      differentiation and development.

PMID- 12513808
TI  - [p73 gene expression in apoptotic process of acute myeloid leukemia cell line
      U937 induced by methotrexate].
AB  - The purpose of this investigation was to study the variation of p73 gene
      expression in the apoptotic process of acute myeloid leukemia (AML) cell line
      U937 induced by methotrexate (MTX). Morphological changes of apoptotic cells were
      observed with microscopy and Wright's + Giemsa staining. DNA ladder and cell
      cycle were examined by agarose gel electrophoresis and flow cytometry
      respectively. Using semi-quantitive reverse transcription-polymerase chain
      reaction (RT-PCR), the expression of p73 mRNA was examined. Results showed that
      MTX could induce U937 cell apoptosis effectively. Condensed nuclei, fragmentation
      of chromosome and DNA ladder were seen after 6 hour following treatment of MTX 5
      micro mol/L. Sub-G(1) peak and S + G(2)/M arrest were also determined by FCM, but
      the quantity of p73 expression was generally constant. In conclusion, U937 cell
      apoptosis induced by MTX did not change p73 mRNA level.

PMID- 12513809
TI  - [Study on the role of PML-RARalpha and RARalpha fusion proteins in NB4 cell
      apoptosis induced by arsenic trisulfide].
AB  - In order to study the role of PML-RARalpha fusion gene and its expression product
      during apoptotic process in NB4 cells induced by arsenic trisulfide (As(2)S(3)),
      the apoptotic effects of NB4 cells were observed by cell morphology, flow
      cytometry and DNA electrophoresis. The change of PML-RARalpha fusion gene and its
      expression product were also assayed by chromosomal G banding, RT-PCR and Western
      blot. The results showed that arsenic trisulfide induced apoptosis of NB4 cells,
      during this process, PML-RARalpha fusion gene had no significant changes, but the
      expression of PML-RARalpha fusion protein and wild-type RARalpha were all
      reduced. It is concluded that arsenic trisulfide can induce apoptosis of NB4
      cells, the degradation of PML-RARalpha fusion protein and wild-type RARalpha may
      play an important role during apoptotic process.

PMID- 12513810
TI  - [The expression of glutathione s-transferase in leukemic cells and resistance to
      chemotherapy].
AB  - In order to study the relationship between the expression of glutathione S
      transferase (GST) in leukemic cells and the chemoresistance in patients with
      acute leukemia, the expressions of GST activity and GST mRNA were measured
      according to spectrophotometric assay based on the use of 1-choloro-2, 4-dinitro
      benzene and in situ hybridization. The results were studied in correlation with
      some clinical and pathological data. Results showed that: 1. There is no
      significant differences between activities of the enzyme with the different
      leukemia types according to the FAB classification. 2. GST activity and GST mRNA
      expression in the patients, both untreated and relapse, were (4.5 +/- 1.0) U,
      33.3% and (7.9 +/- 15) U, 66.3% respectively. 3. In 56 patients, GST activity was
      1.7 +/- 0.7, 5.9 +/- 2.0 and 9.3 +/- 1.7 U and GST mRNA expression was 13.3%,
      29.7% and 76.6%, respectively, in CR, PR and NR groups. The lowest values of GST
      activity and GST mRNA expression were observed in those patients who achieved
      complete remission. The highest values of GST activity and GST mRNA expression
      were observed in those patients with no response to treatment. It was concluded
      that the expression of GST in patients with acute leukemia is closely related to
      the chemosensitivities clinically. Determinations of GST activity and GST mRNA
      are useful for predicting the chemosensitivities and the prognosis of the
      disease.

PMID- 12513811
TI  - [Comparison of detection of trisomy 8 with fluorescence in situ hybridization and
      conventional karyotype analysis in myelodysplastic syndrome].
AB  - The purpose of this study was to compare the detection of trisomy 8 in
      myelodysplastic syndrome (MDS) patients with interphase fluorescence in situ
      hybridization (FISH) and cytogenetic karyotype analysis. Using Spectrum Green
      labeled chromosome 8 centromere probe, interphase FISH was established. The
      trisomy 8 clones were simultaneously detected in 48 MDS cases with FISH and
      conventional cytogenetic analysis (CCA). Results showed that the CCA revealed no
      significant difference of constitutional proportion between MDS-RA and MDS-RAEB
      with karyotypes of whole +8, partial +8 and one +8. With FISH, detectable rates
      were 66.1% for whole +8. Partial +8 and sole +8 were significantly higher than
      one +8 and complex +8, respectively. The percentages of trisomy 8 were similar in
      MDS-RA and MDS-RAEB. Trisomy 8 was detected in 1 of 15 specimens with normal or
      abnormal karyotype without trisomy 8 by FISH. There was linear correlation
      between the percentages of partial +8 detected by FISH and CCA. Two patients
      received CCA and FISH examination at diagnosis and during treatment, the
      percentage of trisomy 8 was increased with progress of disease. In conclusion,
      our results showed that FISH is a sensitive and accurate technique to detect
      trisomy 8 in MDS patients. It can provide contribute to diagnosis, assessment of
      curative effect and predicting progress of disease in MDS. Clone size of trisomy
      8 does not related to classification of MDS, but sole +8 is seems to see in MDS
      RA frequently.

PMID- 12513812
TI  - [Analysis of selected usage and clonal expansion of TCR Vbeta repertoire of
      peripheral blood T cells in patients with non-Hodgkin's lymphoma].
AB  - To investigate the distribution and clonal expansion of TCR Vbeta subfamily T
      cells in patients with B-NHL and T-NHL, the CDR3 of TCR Vbeta 24 subfamily genes
      was amplified in peripheral blood mononuclear cells from 4 cases with B-NHL and 2
      cases with T-NHL using RT-PCR, and to observe the usage of TCR Vbeta repertoire,
      the PCR products were further labeled with fluorescence and analyzed by genescan
      technique for the CDR3 size, to evaluating clonality of the detectable TCR Vbeta
      T cells. The results indicated that only selected expression of 6-12 Vbeta
      subfamily T cells could be identified in the 6 cases with NHL, and Vbeta1,
      Vbeta8, Vbeta13 and Vbeta19 were expressed in all samples, Vbeta2 and Vbeta16
      could be found in 5 samples, whereas Vbeta4-6, Vbeta10-12, Vbeta15, Vbeta17-18,
      Vbeta20 and Vbeta22-23 were absent in all samples. Genescan analysis showed that
      clonal expansion of T cells could be found in 1-3 Vbeta subfamilies from 2 cases
      with B-NHL and 1 case with T-NHL. In conclusions, the similar selected usage of
      TCR Vbeta subfamily T cells could be found in peripheral blood from patients with
      B and T NHL, clonal expansion of T cells which were considered to be related to
      lymphoma cell antigen could be detected in a part of patients with B or T NHL.

PMID- 12513813
TI  - [The distribution feature of TCR Vbeta repertoire in peripheral blood T cells
      from patients with Ph(+) and Ph(-) CML].
AB  - To investigate the T cell distribution characters of TCR Vbeta repertoire in
      Ph(+) and Ph(-) CML. The 24 subfamilies of the TCR Vbeta genes were amplified in
      peripheral blood T cells from 13 patients with CML (Ph+ b3a2, 5 cases; Ph+ b2a2,
      5 cases; Ph(-), 3 cases) by RT-PCR, to analyze the usage of Vbeta subfamilies in
      different CML patients. The results showed that the expression pattern of Vbeta
      repertoire was different in normal individuals and in patients with CML which
      only have part of Vbeta subfamily T cells. 4 - 16 (mean 10.2) Vbeta subfamily T
      cells were detected in the Ph+ b3a2 CML, 8 - 11 (mean 8.8) Vbeta subfamily T
      cells in the Ph(+) b2a2 CML and 5 - 6 (mean 5.7) in Ph(-) CML. Moreover, the
      expression of Vbeta subfamily T cells was different among these three types
      CML.Vbeta10 and Vbeta16 were detected in the all cases with Ph(+) b3a2 and Ph(+)
      b2a2 CML, whereas Vbeta9 and Vbeta22 could be found in the most cases with Ph(+)
      b3a2 CML or Vbeta24 and Vbeta8 in Ph(+) b2a2 CML. In patients with Ph(-) CML,
      Vbeta24 were detected in all samples, and Vbeta9, Vbeta10, Vbeta13 and Vbeta22
      were found in the most cases. The results suggest that skew distribution of TCR
      Vbeta subfamily T cells was existed in peripheral blood of Ph(+) and Ph(-) CML
      patients. The selected usage of TCR Vbeta is different in various types of CML
      patients. It may relate to difference of CML cells associated antigen and
      individual special immunity reaction.

PMID- 12513814
TI  - [The experimental study on the idiotypic nucleic Acid vaccine constructed from
      the genomic DNA to lymphoma].
AB  - This study was to investigate the anti-lymphocytic malignancy immunologic effects
      induced by two types of the idiotypic nucleic acid vaccines which were
      constructed from the genomic DNA and RNA of the human B lymphoma cell line
      respectively. Namalwa cell line and BALB/c mice were used as the models. The gene
      fragments of the IgH variable region (IgHV), which were obtained from the genomic
      DNA and RNA of Namalwa cell respectively, were cloned into the eukaryocytic
      expression vector pcDNA 3.0 to be used as the idiotypic nucleic acid vaccines.
      After transfecting COS cells with one of vaccines constructed from the genomic
      DNA by using LipofectAMINE, the result of transcription was identified by using
      RT-PCR. The experimental mice were immunized by intramuscular injection with two
      types of vaccines. The specific anti-idiotypic antibody was detected by indirect
      immunofluorescence assay. The results showed that the nucleic acid vaccine
      constructed from the genomic DNA can be transcribed in COS cells, the
      transcription product turned shorter, and the intron region of 86 bp was spliced
      accurately. When immunizing the mice, two vaccines both induced the anti
      idiotypic antibody against Namalwa cell, the anti-idiotypic antibody could be
      detected since detected since after immunization, and got to the peak of titer on
      the sixth week. It was concluded that the nucleic acid vaccines against lymphoma
      can be constructed from both the genomic DNA and RNA.

PMID- 12513815
TI  - [Application of bioptic bone marrow imprint in diagnosis of anemia].
AB  - In order to explore the application of bone marrow imprint in diagnosis of
      anemia, sixty-five diagnosed anemia cases were analyzed with bone marrow imprint,
      bone marrow biopsy and bone marrow smear. The result showed that the diagnostic
      rates of bone marrow imprint and biopsy were both significantly higher than bone
      marrow smear, especially in the cases with myelofibrosis, aplastic anemia and
      metastatic carcinoma in bone marrow (P < 0.01). There was no significant
      difference between bone marrow imprint and biopsy, however the bone marrow
      imprint observed more clearly and more simple and convenient than the bone marrow
      biopsy. It is concluded that bone marrow imprint is important for diagnosing
      anemia.

PMID- 12513816
TI  - [Frequency of donor TNF-alpha gene polymorphism in patients with graft versus
      host disease following hematopoietic stem cell transplantation].
AB  - To study the effect of donor TNF-alpha gene polymorphism on severe acute and
      extensive chronic graft versus host disease (GVHD), TNF-alpha gene polymorphism
      was analyzed by denaturing high performance liquid chromatography (DHPLC) and DNA
      sequencing in twenty-one patients with III/IV degree acute GVHD and twenty-seven
      patients with extensive chronic GVHD. The results showed that the frequency of
      TNF-alpha-308 (G/A) significantly increased in patients with III/IV degree acute
      GVHD compared to 0/I degree aGVHD patients (8/21 vs 1/28) (P < 0.01) and the
      frequency of TNF-alpha-308 (G/A) is significantly higher in patients with
      extensive chronic GVHD than in patients without chronic GVHD (7/23 vs 1/17) (P <
      0.05). However, the frequency of TNF-alpha-238 (G/A) does not significantly
      changed in patients with III/IV degree acute GVHD and extensive chronic GVHD. In
      conclusion, the TNF-alpha-308 (G/A) is likely to contribute to high risk for
      III/IV degree acute GVHD and extensive chronic GVHD.

PMID- 12513817
TI  - [Impact on IL-2 expression of lymphocytes in donors after G-CSF administration
      and its clinical significance].
AB  - In this study, to investigate the effect on expression of IL-2 in lymphocytes
      from bone marrow and peripheral blood of normal donors after they were mobilized
      by G-CSF in allo-BMT, 7 normal donors bone marrow and peripheral blood were
      harvested before and after G-CSF administration. The separated lymphocytes were
      measured by FCM after they were stained intracellularly by anti-IL-2, and their
      expressions of IL-2 were compared. The degree of aGVHD in patients after bone
      marrow transplantation was evaluated clinically, and it was compared with the
      status of aGVHD of 15 patients whose donors didn't receive G-CSF administration
      in our department, and 2 groups of patients are comparable in age, types of
      diseases and status of donors. The results showed that the expression of IL-2 in
      lymphocytes in 7 G-CSF mobilized donors decreased significantly after G-CSF
      administration and more severe aGVHD than grade II didn't develop in these
      recipient patients, and comparing with 15 patients received the bone marrow from
      donors who didn't receive G-CSF, the incidence of aGVHD decreased. It is
      suggested that the expression of IL-2 in lymphocytes was influenced by donors' G
      CSF administration, and it is likely that thereby reduces the incidence of aGVHD
      in patients after BMT.

PMID- 12513818
TI  - [Rich hematopoietic stem/progenitor cells in the human placenta tissue and
      placenta blood].
AB  - Clinical transplantation evidence has indication that umbilical cord blood (UCB)
      can be useful in the hematopoietic reconstitution in the children, but not well
      in the adult patients because of the low cell count. The purpose of our study was
      to evaluate a new method for collection of blood cells from human placenta and
      umbilical cord. We have simultaneously harvested blood cells from umbilical cord
      (UCB), placenta blood (UPB) and placenta tissue (UPT) for their content of
      nucleated cells, CD34 (hematopoietic stem progenitor marker) positive cells.
      Result showed that the nuclear cell (NC) from UPB and UPT has three to four times
      than that from umbilical cord blood only, (8.3 +/- 1.04) x 10(8) (UCB), (16.33 +/
      5.54) x 10(8) (UPB), and (8.01 +/- 2.64) x 10(8) (UPT). CD34(+) cells are (0.77
      +/- 0.01) x 10(6), (1.25 +/- 0.55) x 10(6) and (4.21 +/- 1.90) x 10(6)
      respectively. The cells from UPB and UPT have more survival ability than the
      cells from UCB in the long-term cell culture condition. It is clear that the
      blood stored in the liquid nitrogen did not show large loss of total nucleated
      cell count and CD34(+) cells. It was observed that UPT and UPB contained more
      suppressor lymphocytes, which may be important in prevention of graft-versus-host
      disease. In conclusion, our data may have implications for the development of
      placental blood collection together with umbilical cord blood banking for the
      stem cell transplantation.

PMID- 12513819
TI  - [Establishment of a method for HLA-DRB genotyping in cord blood by reverse dot
      blot hybridization technique].
AB  - The HLA system was discovered by virtue of the fact that it was polymorphic. The
      impetus for its discovery was the search for polymorphic antigens to match for
      transplantation, by analogy with the human red cell blood groups. The most
      usually DNA method of HLA typing is sequence specific oligonucleotides (SSO) and
      PCR sequence specific primers (SSP). SSO technique is perfectly suited for
      analyzing large number of samples, it is not suitable for individual or small
      numbers. The SSP method is ideal for typing individual samples, but it is costly
      and requires high capacity thermal cycles for larger numbers of samples. To set
      up a simple, quick, cheap and high resolution DNA method, were collected sixty
      three cord blood samples from Guangzhou Cord Blood Bank, got DNA from blood by
      the traditional guanidine hydrochloride distillation method. Each sample was
      simultaneously typed by SSOP, PCR-SSP and reverse dot-blot hybridization (RDB)
      methods. All of typed is success. The results of three DNA methods are consistent
      each other. 60 HLA-DRB1 alleles could be accurately distinguished with the RDB
      method. Our results show that RDB method is a simple, quick, cheap and high
      resolution method for HLA-DRB types. It can be used in any HLA typing.

PMID- 12513820
TI  - [New tactics of human red blood cells stored at 4 degrees C-protective effect of
      antioxidant solution on red blood cells damage].
AB  - Aliquots of venous blood from healthy donor were collected in plastic blood
      storage bags with ACD, GMA or antioxidant solution (superoxide dismutase, SOD),
      respectively, and stored at 4 degrees C. After storage for varying periods, the
      parameters of the blood were detected in the blood samples. Results showed that
      the parameters of the blood stored at 4 degrees C for 75 days in SOD group were
      following: the recovery of RBC-Hb was 87.2%, plasma-Hb (mg/L) was 193.2, P50
      (mmHg) was 34.0 (normal value was 33.1); deformability (DImax) was 0.2413 (74.3%
      of normal value). There was no evident hemolysis, color change, air bubble and
      clots. It was concluded that human RBC stored at 4 degrees C for 75 days with SOD
      solution, recovery of levels of RBC-Hb and plasma-Hb were accorded with the
      requirements of "Basic Demands of Blood Station" in China.

PMID- 12513821
TI  - [Comparison of leucocyte-reduced platelet concentrates produced with spectra
      version 5.1 and version 7.0 blood cell separators].
AB  - In the present study, the performance of a new blood cell separator (COBE Spectra
      LRS Turbo Version 7.0) and that of the previous version LRS version 5.1 in the
      collection efficiency (CE), collection rate and residual white blood cells during
      platelet collection from donors were compared. 232 units of platelet concentrates
      (n = 232) were evaluated and 163 units were collected with the Spectra LRS
      version 5.1 (Group A) and 69 units with the LRS turbo version 7.0 (Group B).
      Donor's blood cell counts and parameters, platelet yield, collection efficiency
      and residual leukocytes in platelet concentrates were analysed. Results showed
      that the platelet yield was higher in group B than that in group A: (2.90 +/-
      1.1) x 10(11) versus (2.58 +/- 1.2) x 10(11), P < 0.001; residual WBCs were less
      than 5 x 10(6) in 99.4% of group A platelet concentrates and in 97.1% of group B
      platelet concentrates. Collection efficiency was higher in group B than in group
      A: 51.4 +/- 8.7 versus 43.6 +/- 6.3. A correlation between platelet count before
      collecting blood and platelet yield was observed in both groups. In conclusion,
      the Spectra LRS Turbo version 7.0 showed a higher platelet yield than that with
      LRS version 5.1. Higher platelet counts before collection allow a higher platelet
      yield.

PMID- 12513822
TI  - [Progress on the study of tissue stem cells].
AB  - Stem cells in the individual life are the cell population with high self-renewal
      capacity and multiple differentiation potential. At present, embryonic stem cells
      and tissue stem cells are the major objects for study in the field of stem cell
      engineering. At the same time, with the development of tissue engineering, cell
      replacement therapy became a new approach to treat some diseases. Tissue stem
      cells were tried to expand and committedly induce in vitro to some cells that are
      needed, then implanted them into patients to repair damage, replace regressive
      tissue and improve the function of hereditarily defect tissue. Based on recent
      progress of research on stem cells, this paper reviewed the biological characters
      and clinic application prospects of tissue stem cells.

PMID- 12513823
TI  - [The update achievements on the relation between free radical and leukemia].
AB  - Free radicals are a group of charged atoms, molecules or ions with strong
      biological activity, which play an important role in pathogenesis of cancers and
      many other diseases. Free radicals are produced and consumed by a serial of chain
      reactions. Free radicals can activate pro-oncogenes, impact the signal
      transduction about the apoptosis, survival and proliferation of tumor cells
      modify the key enzymes or proteins functions, and might cause carcinogenesis.
      Meanwhile, free radicals damage the tissues and organs and bring about a variety
      of pathological changes. On the other hand, free radicals are involved in the
      effects of some anti-leukemic drugs as intermediates or functional substances.

PMID- 12513824
TI  - [Progress of chimerism research after allo-bone marrow transplantation].
AB  - Bone marrow transplantation (BMT) is an effective therapy for a variety of
      hematologic and immunodeficient diseases. Two possible situations of chimerism
      can be encountered when assessing the hematological status in recipient post-allo
      BMT: 1. complete chimerism, where the marrow and circulating blood cells all are
      donor origin; 2. mixed chimerism, the cell components in recipient are both donor
      and recipient origins. Formation of the different kinds of chimerism are
      influenced by some factors, included the amount of infused hematopoietic stem
      cells, the ratio of T cells from donor and recipient, conditioning regimen and
      patient's condition. The clinical significance was different for the forms and
      development of chimerism. There are several detecting methods for chimerism, such
      as microsatellite assay, karyotyping of chromosome, conversion of blood group,
      red blood cell antigen, restriction fragment length polymorphism, variable number
      of tandem repeat, and PCR. Above-mentioned aspects of chimerism research were
      reviewed.

PMID- 12513825
TI  - [Study on the immunophenotypes of bone marrow cells from patients with
      myelodysplastic syndromes and its clinical implications].
AB  - The phenotypes of the bone marrow cells in various subtypes of myelodysplastic
      syndromes (MDS) and its clinical implication were explored. The antigen
      expression of a panel of antigens expressed in marrow cells from 30 patients with
      subtypes of MDS was assayed by alkaline phosphatase anti-alkaline phosphatase
      method. The results showed that the expression of myeloid antigens appeared
      abnormality, CD13 and CD33, found on granulocyte and macrophage precursors,
      increased, and CD15 decreased. There were no significant changes for monocytic
      antigen CD14 and lymphoid antigens CD7 and CD10. CD34 was increased in RAEB/RAEB
      t and was not increased in RA/RAS patients. CD71, expressed by erythroblast and
      proliferative cells, was higher in all subtypes of MDS than that in control
      group. It is suggested that the bone marrow cells from MDS patients showed
      abnormality of more than two series of immunophenotypes, detection of
      immunophenotype in MDS cells might be contributed to the diagnosis and predicting
      prognosis.

PMID- 12513826
TI  - [Primary central nervous system lymphoma: report of one case].
AB  - One case of primary central nervous system lymphoma was reported. The patient
      received comprehensive therapy, mainly the surgical treatment, with the survival
      time 12 months, and local recurrence was considered as the major cause of death.
      The pathology, imagine examination, diagnosis and treatment of primary central
      nervous system lymphoma were discussed.

PMID- 12513827
TI  - [Flowcytometric-immunophenotyping for leukemia needs to be standardized].
AB  - Flowcytometer has been flourishing since the passed decade in our nation. Many
      general hospitals use it for routine tests. One of the main usage is
      immunophenotyping for hematological malignancies. Flowcytometric
      immunophenotyping (FCM-IM) facilitates accurate diagnosis in both leukemias and
      lymphoid proliferative disorders (LPDs). It becomes an indispensable criteria in
      the diagnosis of hematological malignancies. It may also offer additional
      therapeutically relevant information. Typical patterns of immunophenotype in
      leukemias and certain types of LPDs are illustrated in figure 1 and figure 2. But
      variation or overlapping appears often. In order to reach a definitive diagnosis
      and to have a common interpretation between laboratory to laboratory the
      following items need not to be ignored: 1. Direct staining and multi-color or
      multi-parameter flow cytometric analysis is necessary. 2. The phenotype of
      abnormal cells should be determined on as pure a population as possible therefore
      CD45/SSC gating is critical for isolating the blast population (abnormal cells).
      CD45/SSC gating is much better than FSC/SSC gating especially when percentage of
      blast is low in the sample. Else, each subtype of leukemia has its special
      CD45/SSC pattern. 3. The phenotype of this certain population should be described
      clearly but it is not necessary to count the percentage of each marker. 4. > 20%
      for positive threshold used in indirect staining method may be confused in multi
      color direct staining method. 5. Hybrid leukemia diagnosed by FCM only should be
      in caution since the divergence of antigen/antibody, the lineage infidelity of
      antigen expression and the biological characteristics of the leukemic cells.
      Flowcytometer is not a cell counter. "It provides a pattern of information that
      must be interpreted by a knowledgeable professional in the context of the
      clinical situation".

PMID- 12513828
TI  - Effects of erythropoietin and recombinant cytokines on colony formation and self
      renewal by erythroid burst-forming units and granulocyte-macrophage progenitors
      from mobilized peripheral blood progenitor cells.
AB  - The effects of erythropoietin and recombinant cytokines (G-CSF, SCF, IL-3 and GM
      CSF) on colony formation and self-renewal by erythroid burst-forming units (BFU
      E) and granulocyte-macrophage progenitors (CFU-GM) from mobilized peripheral
      blood progenitor cells (PBPCs) of the normal donors and patients were
      investigated. To better understand how combinations of the cytokines may be
      appropriate for stem cell manipulation, a model involving replating of individual
      BFU-E and CFU-GM colonies has been used to study the effects of cytokines on
      colony formation and self-renewal. Based on granulocyte colony-stimulating factor
      (G-CSF) and erythropoietin(EPO) alone serve as a baseline with which to compare
      the effects of the combinations with stem cell factor (SCF), interleukin-3 (IL-3)
      or granulocyte-macrophage colony-stimulating factor (GM-CSF). The results
      revealed that: 1. BFU-E derived from PBPCs produced a significantly great numbers
      of subcolonies in EPO plus IL-3 and EPO+SCF+IL-3, and a difference in EPO+SCF
      compared with EPO alone. 2. Compared patients to normal donors the self-renewal
      ability of BFU-E was not influenced after EPO plus SCF or IL-3. 3. There was a
      significantly increased frequency of CFU-GM in the presence of SCF, IL-3, and GM
      CSF used in conjunction with G-CSF. Comparing the frequencies of CFU-GM in
      patients and donors, patients' PBPCs were more sensitive to G-CSF+SCF and GMix (G
      CSF+SCF+IL-3+GM-CSF), especially to G-CSF alone than donors. 4. There was a
      significant increase in AUC (area under the curve of subcolony distribution) in
      the presence of G-CSF combined with other cytokines. GMix was identified as the
      optimal combination of cytokines for both the expansion of CFU-GM as well as the
      expansion of clonogenic progenitor cells. 5. Donors have a high AUC than
      patients, especially there was a significant increase AUC in G-CSF alone (P =
      0.0067).

PMID- 12513829
TI  - [Expression and function of CD95/fas antigen and Bcl-2 on cord blood
      hematopoietic progenitor cells].
AB  - The cell-surface expression and functional status of the CD95/Fas antigen on
      primitive hematopoietic progenitors isolated from human cord blood were studied.
      The CD34(+) cells freshly isolated from cord blood displayed low CD95 expression,
      combinations of cytokines such as SCF+FL upregulated the expression of CD95 in
      CD34(+) cells. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) further increased the CD95 expression induced by positive cytokines. The
      functional status of CD95-mediated apoptosis was analysed by incubation of
      CD34(+) cells in the presence of anti-CD95 monocloned antibody (McAb). The effect
      of anti-CD95 McAb was measured by viable cells counting, flow cytometry, LTC-IC
      and CFU-C assays. Viable cells and CFU-C numbers were 31.9 +/- 11.2 and 43 +/-
      2.0 respectively, the rate of apoptosis was 42.9 +/- 12.4 in the presence of anti
      CD95 McAb and TNF-alpha or IFN-gamma. However, growth factor deprivation or the
      early-acting cytokine such as SCF and FL cross-linking of CD95 lead to low
      apoptosis of CD34(+) cells. The correlation of increased intracytoplasmic levels
      of Bcl-2 and the presence of CD95 on surface of CD34(+) cells suggests that Bcl-2
      may be involved in protecting against CD95-mediated apoptosis of cord blood
      CD34(+) cell.

PMID- 12513830
TI  - [Detection of cytoplasmic antigens by flow cytometry and its implication for
      leukemia immunophenotyping].
AB  - The purpose of this study was to optimize a fixation procedure for detection of
      cytoplasmic antigens by flow cytometry(FCM) and to evaluate the effect of
      intracellular CD3, CD22, CD79a and myeloperoxidase(MPO) in lineage assignment.
      Four kinds of fixation procedure and three or four color direct
      immunofluorescence staining were used to permeate cell membrane and label cell
      surface and intracellular antigens by means of FCM. Results showed that
      percentage of cytoplasmic antigens positive cells was the highest and cell
      scatter and fluorescence intensity of CD45 were not changed after using of FACS
      permeabilization solution. MPO protein was positive in 16/18 acute myeloid
      leukemia(AML) patients. 4 cases of T cell-acute lymphoblastic leukemia (T-ALL)
      cases were positive for cytoplasmic CD3(c CD3) but surface CD3 was negative. c
      CD22 was only detected in 9/13 of B-ALL and cCD79a was positive in 5/5 B-ALL.
      18/38 cases of acute leukemia were expressed in more than one lineage marker,
      8/21 cases of acute non-lymphocytic leukemia(ANLL) were CD7 positive. 7/17 cases
      of acute lymphocytic leukemia (ALL) expressed CD13. After further cytoplasmic
      antigen detection, one was considered to be a T/myeloid biphenotypic leukemia,
      another one was diagnosed as biclonal or mixed leukemia. The results suggest that
      intracellular CD3,CD22,CD79a and MPO are lineage specific markers, they are very
      important for biphenotypic and biclonal/mixed acute leukemia identification

PMID- 12513831
TI  - [Expression of alpha subunit for IL-6 receptor at mRNA and protein levels in
      human leukemic cells].
AB  - To probe into the expression of alpha subunit for IL-6R at both mRNA and protein
      levels in human leukemic cells and to discuss its implication in targeted
      treatment for leukemia with recombinant IL-6-PE40 exotoxin fusion protein
      mediated by IL-6/IL-6R system, semi-quantitative RT-PCR, sequencing and FCM were
      used to analyze the gene and protein expression levels of alpha subunit for IL-6R
      in leukemic cells. Our results showed that not only mRNA but also protein of
      alpha subunit for IL-6R are highly expressed in the myelogenous leukemic cell
      lines, the relative expression levels of mRNA were KG-1(1.22) > (1.02) >
      U266(1.00) > U937(0.99) > HL-60(0.76). Among lymphoblastic leukemic cell lines,
      Raji expressed a certain amount of alpha subunit mRNA (0.77), whereas its alpha
      subunit protein was not detected. Expression of alpha subunit mRNA and protein
      were negative in lymphoblastic leukemic cell lines, HuT28 and CEM, and chronic
      myelocytic leukemic cell line K562. These results correlate with those of FCM
      highly. Noteworthily, normal human peripheral blood mononuclear cells expressed
      hardly protein of IL-6R alpha subunit. So this study provides sufficient
      experimental evidence that the targeted treatment by recombinant IL-6-PE40 can
      specifically kill leukemic cells highly expressing IL-6R without toxicity to
      normal hematopoietic cells.

PMID- 12513832
TI  - [Antisense oligonucleotide of rat gp130 blocked the inhibitory effect of rhIL-6
      on proliferation of the rat acute myeloid leukemia cell line R2 in vitro
      cultures].
AB  - The second nonligand binding chain of IL-6 receptor (IL-6R), the membrane
      glycoprotein with 130 kD mol wt (gp130), is responsible for the signal
      transduction of IL-6 biological activity. Our experiments indicated that the rat
      gp130 molecule, which was expressed in the rat acute myeloid leukemia cell line
      R2, could associate with the complex of rhIL-6 and membrane human IL-6R molecule
      and transduce the inhibition-inducing signal on R2 cells. In the present study,
      antisense oligonucleotides of rat gp130 were synthesized and uptaked into the R2
      cells. Then the effects of the antisense or sense nucleic acids of rat gp130 on
      the inhibition induced by rhIL-6 in the R2 cell were investigated. Our results
      show that the antisense oligonucleotide of rat gp130 blocked the inhibitory
      effect of rhIL-6 on the R2 cells by (45 +/- 7)% at the optimal concentration

PMID- 12513833
TI  - [p21(WAF1) transfection decreases sensitivity of K562 cells to VP-16].
AB  - The objective of this study was to explore the effect of p21(WAF1) on the
      sensitivity to chemotherapeutic agent VP-16, etoposide, in leukemia cell line
      K562. A p21(WAF1) retroviral expression vector was constructed, and mediated by
      FuGENE(TM)6, it was transfected into K562 cells, which without p21(WAF1)
      expression. The ecotropic expression of p21(WAF1) in K562 cells was identified by
      RT-PCR and Western blot, and named K562-p21(WAF1) cell. The K562-p21(WAF1) cells
      were exposed to VP-16 at different concentrations and different times, then, the
      sensitivity to VP-16 was examined by cell viability and MTT assay, the apoptosis
      induced by VP-16 was examined by DNA fragments electrophoresis and flow
      cytometric Annexin V-PI dual labeling technique. The results showed that the
      ecotropic expression of p21(WAF1) decreased the sensitivity of K562 cells to VP
      16. After treatment of VP-16, the DNA ladder was examined in control K562-neo
      cells at 20 microgram/ml, but in K562-p21(WAF1) cells at 80 microgram/ml. With
      FCM, the number of apoptotic K562-neo cells was 14.9% and 25.4% respectively
      after treated with 20 microgram/ml VP-16 for 12 and 24 hours, and it was 6.94%
      and 10.96% in K562-p21(WAF1) cells. Our results suggest that the expression of
      p21(WAF1) could reduce the sensitivity of K562 cells to VP-16 and inhibit the
      apoptosis of K562 cells

PMID- 12513834
TI  - [The expression of Fas, FasL and Bcl-2 on RMA cells during the process of
      apoptosis induced by chemotherapeutic drugs].
AB  - The objective of the study is to explore the effect of Fas, FasL and Bcl-2 on the
      process of apoptosis induced by chemotherapeutic drugs through detecting the
      expression of Fas, FasL and Bcl-2 on murine lymphoma cell line RMA.
      Dexamethasone(DEX), etoposide (VP-16), arsenic trioxide As(2)O(3) and all trans
      retinoic-acid (ATRA) were added to the RMA cells as well as to the cells
      preincubated with interleukin-2 (IL-2), interleukin-6 (IL-6) or granulocyte
      macrophage colony-stimulating factor (GM-CSF), respectively. The effect on
      apoptosis was observed and the expression of Fas and FasL mRNA as well as the
      expression of Fas and Bcl-2 antigen were measured. DEX and VP-16 could promote
      apoptosis of RMA cells while upregulating the expression of Fas and FasL without
      affecting the expression of Bcl-2. ATRA downregulated the expression of Bcl-2
      without any change of Fas and FasL, and no apoptosis of RMA cells induced by ATRA
      was observed. Although As(2)O(3) induced apoptosis of RMA cells, it did not
      affect the expression of Fas, FasL and Bcl-2, which suggested that different
      drugs induce apoptosis of the same kind of cells by different signal transduction
      system and apoptosis induced by Fas system needed the coexistence of Fas and
      FasL. Although IL-2, IL-6 and GM-CSF upregulated the expression of Fas protein
      when adding to RMA cells separately, none of them induced apoptosis. Apoptosis
      could be induced by combination of IL-2 and IL-6 along with the upregulation of
      Fas and FasL. The cytokines facilitated the apoptotic action of chemotherapeutic
      drugs, the drug concentration for inducing apoptosis decreased and the time
      period of starting apoptosis shortened. Apoptosis could be observed without the
      expression of FasL when anti-Fas-antibody was added to RMA cells. The results
      demonstrated that there was synergistic effect of chemotherapeutic drugs and some
      cytokines for induction of apoptosis. Fas-FasL system participated in the
      apoptosis induced by DEX and VP-16; different drugs induce apoptosis by different
      pathway of signal transduction.

PMID- 12513835
TI  - [Study about proliferation and apoptosis of megakaryocytes in patients with
      myelodysplastic syndromes].
AB  - In order to observe the proliferative and apoptotic situation of megakaryocytes
      in patients with myelodysplastic syndromes (MDS). CD41 immunoenzyme labeling
      (alkaline phosphatase anti-alkaline phosphatase APAAP)/DNA in situ end labelling
      (ISEL) double stained techniques was used onto plastic cold embedded bone marrow
      sections in 29 MDS patients to analyse the proliferative and apoptostic
      characterization of megakaryocytic line with 14 cases of iron deficient diseases
      (IDA) as control. The results showed that the mean CD41 positive cell number in
      MDS group was (26.23 +/- 8.18) /mm(2) with a count of (15.64 +/- 7.11) /mm(2) in
      control group (p < 0.05). The small-micro megakaryocytes in MDS is much higher
      than that in IDA group (P<0.01). There was a positive co-relation between total
      megakaryocytes and small-micro megakaryocytes count in MDS (r = 0.702, p<0.01).
      Some megakaryocytes distributed abnormally around trabecula and formed small or
      large clusters. Apoptotic megakaryocytes in MDS occupied 4.40% and 9.32% of all
      CD14 positive cells and all apoptotic cells respectively (p > 0.5 comparing with
      control). Apoptosis in megakargocytic line occurred only in small-micro
      megakaryocytes and showed positive co-relation to the number of micro
      megakaryocytes. Some apoptotic cell with morphologic characters of megakaryocytes
      expressed no CD41. It is concluded that overproliferation of megakaryocytes
      exists in MDS. Apoptosis occurring in micro-megakaryocytes may be a kind of
      physiological response to abnormal megakaryopoicsis in MDS. No obvious increased
      apoptosis of megakaryocytes in MDS was found perhaps due to lack of surface
      antigens CD41 in some later stages of apoptotic cell.

PMID- 12513836
TI  - [Correlation of bone marrow stromal function in vitro with efficacy of
      anisodamine therapy for aplastic anemia].
AB  - To observe normal bone marrow stromal function for supporting hematopoiesis and
      realize the correlation of bone marrow stromal function in patients with aplastic
      anemia (AA) and anisodamine therapy, normal human marrow CFU-GM was assayed on
      bone marrow stromal layer (SL) formed on week 3 culture, and the CFU-GM without
      SL as a control (100%). Results showed that the production of CFU-GM on the
      normal SL was significantly higher than that of the control. The production of
      CFU-GM on the SL of 4 AA patients, who responded to anisodamine, was < 80% of the
      control, and when 2 of them were reexamined for stromal function after treatment,
      the number of CFU-GM on SL rose up to 168.8% and 249.2% from 38.7% and 39.7% of
      the control respectively. While in the rest 6 patients, the number of CFU-GM was
      > 80% of the control, only one patient was improved by anisodamine therapy. So,
      normal bone marrow stromal layer can obviously support the growth of
      granulocyte/macrophage progenitor cells. Anisodamine therapy could be an
      effective agents for aplastic anemia with stromal dysfunction

PMID- 12513837
TI  - [The effects of sera from patients with paroxysmal nocturnal hematoglobinuria on
      the growth of CD34(+) cells].
AB  - To investigate the effects of sera on the growth of single CD34(+) cells from
      patients with paroxysmal nocturnal hematoglobinuria (PNH), sera from both PNH
      patients and normal individuals were added separately to the single cell culture
      system and semi-solid colony formation system. The growth of the normal CD34(+)
      and PNH CD34(+) CD59(+) and CD34(+) CD59(-) cells was evaluated. No growth
      difference was found for growth of the normal CD34(+) and PNH CD34(+) CD59(+)
      cells when PNH or normal sera were added to the culture media in either single
      cell culture or colony formation culture. While no difference was detected for
      single PNH CD34(+) CD59(-) cells growth when PNH or normal sera were added, more
      colonies were observed in semi-solid culture with PNH sera. A conclusion was
      reached that compared with those from normal controls, the sera from PNH patients
      had no significant influence on single hematopoietic stem/progenitor cells
      derived from normal subjects and from PNH patients, but the PNH sera might
      promote the colony formation of the CD34(+) CD59(+) cells in semi-solid culture

PMID- 12513838
TI  - [The feature of TCR V alpha40 with Jdelta1, Ddelta3 or psiJalpha gene
      rearrrangements in T cells].
AB  - The rearrangement segments of TCR Valpha40 gene with Jdelta1, Ddelta3 or psi
      Jalpha were amplified in genomic DNA from peripheral blood mononuclear cells of
      10 normal subjects, sorted CD3(+) cells from peripheral blood of 4 cases and
      thymocytes from 7 cases, by using nested PCR. Different amounts of DNA from all
      samples were amplified to estimate the frequency of Valpha40 gene rearrangements.
      The results indicated that the rearrangements of TCR Valpha40 gene with Jdelta1,
      Ddelta3 or psi Jalpha could be found respectively in the most samples of
      peripheral blood T cells or thymocytes. The frequencies of Valpha40
      rearrangements were different in peripheral blood T cells and thymocytes by
      analysis of PCR with different amounts DNA. It is concluded that the TCR V
      alpha40-psi Jalpha was the most frequent rearrangement in mature and immature T
      cells, whereas TCR Valpha40-Ddelta3 was more frequently rearranged in immature T
      cells

PMID- 12513839
TI  - [Apoptosis of the allo-antigen specific T cells induced by CD34(+) cells
      transfected with exogenous gene FasL].
AB  - To investigate the value of apoptosis of the allo-antigen specific T cells
      induced by Fas/FasL pathway in order to prevent GVHD in allo-transplant, the
      CD34(+) cells were transfected with FasL or not, used as effector cells, mixed
      with allo-antigen specific T lymphocytes with presence or absence of IFN-gamma or
      IL-2. After 5 days, apoptosis of T cells was detected by TdT nick end mediated
      dUTP labeling (TUNEL) and flow cytometry. The effects of IFN-gamma or IL-2 on
      apoptosis of CD34(+) cells of graft induced by Fas/FasL pathway observed as
      controls. The apoptosis incidence of T cells was (12.1 +/- 1.5)% when CD34(+)
      cells transfected with FasL were used as effector cells, that was much higher
      than that T cells with CD34(+) cells non-transfected (p < 0.01). In the presence
      of IFN-gamma or IL-2, apoptosis incidence reached to (20.1 +/- 2.3)% or (17.6 +/-
      1.3)% respectively (p < 0.01). When sFasL was added to CD34(+) cells freshly
      isolated or induced with IFN-gamma or IL-2, the incidence or apoptosis of CD34(+)
      cells was (7.8 +/- 0.8)%, (18.7 +/- 1.6)% (p < 0.01) or (7.9 +/- 1.0)% (P > 0.05)
      respectively. The results suggest that it is possible to induce apoptosis of the
      allo-antigen specific T cells in grafts activated by allo-antigen by exogenous
      Fas ligand expressed on receptor cells and that may hopefully provide a new
      method to prevent GVHD

PMID- 12513840
TI  - Pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic
      stem cell transplantation.
AB  - Six out of 20 patients undergoing a major ABO-incompatible allogeneic stem cell
      transplantation (allo-HSCT) developed pure red cell aplasia (PRCA), which did not
      show any effects on granulocyte and platelet engraftment, and incidence of grade
      II-IV aGVHD. All the 6 cases of PRCA were in blood group O recipients of grafts
      from blood group A donors (n = 5) or blood group B donor (n = 1), suggesting that
      donor/recipient pair (A/O) is associated with a high risk of PRCA after major ABO
      incompatible allo-HSCT. Erythroid engraftment occurred spontaneously in four
      cases without specific intervention other than the RBC transfusion, which
      coincided with the decrease of isoagglutinin titers below 8, and the remaining 2
      patients with prolonged erythroid aplasia( > 300 days) despite therapy with
      erythropoietin (EPO) were successfully treated by plasma exchange with donor-type
      plasma replacement. Cyclosporine did not appear to have played any role in
      causing PRCA in our patients, however, the occurrence of GVHD may facilitate the
      recovery of erythropoiesis.

PMID- 12513841
TI  - [Flow cytometry combined assay for phosphatidylserine and CD62p expressed by
      preserved platelets].
AB  - Human platelets have distinct characters when preserved by different methods. A
      efficient flow cytometric assay for different preserved platelets expression of
      CD62p and phosphatidylserine(PS) is in dire need. Efficient flow cytometric assay
      for CD62p and PS expressed by preserved platelets was established and the major
      conditions were optimized. The platelets need not to be washed to wipe off plasma
      and can be labelled diredtly during the sample preparation. It is efficient for
      flow cytometric analysis when fresh platelet riched plasma (FPRP) was set as
      negative control, thrombin actived FPRP, and liquid nitrogen treated FPRP were
      set as positive control respectively. Gly-Pro-Arg-Pro acetate salt (GPRP) was
      applied to prevent platelets aggregation and fibrin formation, stabilize
      platelets and minimize the artificial platelets activation. This is also the key
      to conquer difficulty of flow cytometric quantitive analysis when platelet,
      Ca(2+) and plasma coexist. This flow cytometric method is specially suitable for
      the multi-parameter assay including PS expression for cryopreserved platelets.
      Minimal sample manipulation, no fixation, and GPRP application resulted in minor
      artifacts and good sample stability. Results suggested, this flow cytometric
      assay for preserved platelets is simple and efficient. In addition, the author
      prepared four different methods treated platelets that can be easily
      distinguished through this flow cytometric assay. It not only makes sure the
      practicability of this flow cytometric assay, but also suggests the value of the
      treated platelets applied in preserved platelets flow cytometric ass

PMID- 12513842
TI  - [In vitro inhibition and mechanism of multiple myeloma cells growth by
      thalidomide].
AB  - To investigate the influence of the thalidomide on the growth of multiple myeloma
      cells from untreated, relapsed or refractory patients and summarize its
      mechanisms, thalidomide influence on colony growth of untreated, relapsed or
      refractory multiple myeloma cells cultured by semisolid methylcellulose was
      observed. The level of interleukin-6 (IL-6) autosecreted by myeloma cells was
      tested by IL-6-dependent cell line when myeloma cells were treated with
      thalidomide at 200 microgram/ml, and in the same concentration of thalidomide the
      expression of IL-6 receptor were tested by flow cytometry. Results showed that
      colony growths of myeloma cell from untreated and relapsed or refractory patients
      were all colonies were inhibited when treated by thalidomide up to 75
      microgram/ml or 100 microgram/ml concentration. The inhibition was concentration
      dependent, higher concentration cause more inhibition. After treatment with
      thalidomide at 200 microgram/ml, the concentrations of IL-6 secreted by myeloma
      cells were (148.5 +/- 96.7) microgram/ml, and the levels of IL-6 receptor
      expressed on the cell surface were 16.7% and 20.2% in untreated and relapsed or
      refractory patients, respectively, and those were significantly lower than those
      levels in the cells before exposure to thalidomide. It was concluded that
      thalidomide can inhibit growth of both relapsed or refractory cells and untreated
      myeloma cells in vitro. Therefore, it can be used to treat untreated multiple
      myeloma patients. Inhibiting tumor cells secreting level of IL-6 and reducing the
      expression of IL-6 receptor on myeloma cell surface is one of the mechanisms for
      thalidomide to remedy multiple myeloma patients

PMID- 12513843
TI  - [Advances in research on cytokine mimetic peptides/non-peptides stimulating
      hematopoiesis].
AB  - Cytokines such as erythropoietin (EPO) and thrombopoitein (TPO) and so on, which
      stimulate hematopoiesis, can regulate self-renewal, proliferation,
      differentiation, maturation and programmed cell death of hematopoietic cells
      through specifically binding to surface receptors. Recently random phage display
      peptide libraries and other screening methods have been used to isolate mimetic
      including small peptides and non-peptides molecules, which can mimic the same
      effects as cytokines, such as EPO and TPO, and demonstrate the similar potency
      and activity as EPO and TPO in a panel of in vitro biological assays and in
      animal experiments. These approaches are critical to further research of
      interactive mechanisms between cytokine and receptor, receptor activation and
      rational design of other desired cytokine mimetic. This review concisely
      introduced recent advances in research on mimetic of EPO, TPO and other cytokines
      and future directions.

PMID- 12513844
TI  - [ATM and Cancer].
AB  - The mutation of AT gene (ATM) leads to the AT disease (ataxia telangiectasis),
      the cancer incidence of AT patients and its carriers are significantly higher
      than the normal persons. And they are easy to have lymphoid tumors, including the
      lymphoma and leukemia et al. These indicate the ATM play a important role in the
      cancers pathogenesis mechanism. The ATM gene locate in the human chromosome 11q22
      23, and the ATM is a kind of nuclear protein, its major functional domain is P13K
      (phosphatidylinositol 3-kinase), locates on the carboxy terminus. ATM protein
      plays a critical role in the signal transduction of cell cycle checkpoint, the
      repair of damaged DNA and the apoptosis. The mutation of the ATM gene leads to
      the functional and structural change of ATM protein in the AT patient, then leads
      to the abnormality of cell cycle checkpoint and the DNA damage repair, the
      apoptosis sensitivity increase. So the AT patients and their cells are
      radiosensitive, the characteristic of AT patient suggests the ATM gene is
      valuable in the cancer's gene therapy

PMID- 12513845
TI  - [The role of human herpesvirus-8 infection in the pathogenesis of multiple
      myeloma].
AB  - Multiple myeloma is a B-cell neoplasm characterized by abnormal proliferation and
      accumulation of monoclonal plasma cells in the bone marrow. Recently some
      laboratories have detected human herpesvirus-8 (HHV-8) DNA sequences in bone
      marrow dendritic cells from myeloma patients. It has been suggested that the
      cytokines expressed by HHV-8 gene, such as vIRF, vIL-8R and vIL-6, may play a
      role in the pathogenesis of multiple myeloma. However, the majority of European
      investigators failed to find evidence to confirm this observation. It remains
      unclear whether HHV-8 is consequentially associated with myeloma or only a
      regional opportunistic infection. Controversy still focuses on the role of
      specific HHV-8 strains involved in pathogenesis of multiple myeloma and causality
      between the

PMID- 12513846
TI  - [Lishengsu promotes the recovery of chemotherapy-induced leukopenia in patients
      with malignant tumors].
AB  - In order to investigate the therapeutic effects of Lishengsu, a domestic
      preparation of recombinant human granulocyte colony stimulating factor, the
      recovery of leukopenia was observed in 58 patients with malignant tumors after
      chemotherapy. In these patients, 7 cases were in first cycle of chemotherapy and
      51 were given in repeated cycles. When blood leukocyte level decreased to less
      than 3x10(9)/L, Lishengsu was subcutaneously injected for 3-5 days at a dose of
      75 microgram or 150 microgram per day. The results showed that Lishengsu
      remarkably alleviated the degree of leukopenis and accelerated the leukocyte
      counts recovered to normal level. The promotive effects of Lishengsu to recovery
      of leukopenia were dependent on degree of leukopenia at start of administration
      of Lishengsu. The curative effect of Lishengsu to chemotherapy-induced leukopenia
      was reliable with slight side-effects

PMID- 12513850
TI  - Ethics of preimplantation genetic diagnosis combined with histocompatibility
      selection to repair sick siblings.

PMID- 12513847
TI  - [Association of the relationship between HLA-DQB1 alleles and major beta
      thalassemia in 42 guangdong Chinese].
AB  - To investigate the relationship between HLA-DQB1* alleles and major beta
      thalassemia, the HLA-DQB1* loci typing was performed with polymerase chain
      reaction-sequence specific primer (PCR-SSP) in 42 unrelated (unconsanguineous)
      patients with major beta-thalassemia and 45 normal control individuals in
      Guangdong Province. Results showed that the frequency of HLA-DQB1*06 allele in
      patient group (19.0%) was higher than that in the control group (4.4%) kappa(2) =
      8.961, p < 0.01). Our data suggests that HLA-DQB1*06 allele is associated with
      pathogenesis of the major beta-thalassemia in Guangdong area.

PMID- 12513851
TI  - Ovarian tissue cryopreservation: therapeutic prospects and ethical reflections.
AB  - Along with improved survival, methods to preserve or restore the fertility
      potential of young women and children treated with cytotoxic chemotherapy or
      pelvic radiotherapy have been developed or are in the offing. Surgery,
      radiotherapy and chemotherapy can all impact on the future ovarian function, but
      patient and disease tailored application and use of preventive measures can limit
      ovarian damage. When the loss of reproductive ovarian function is unavoidable,
      different alternatives to preserve fertility or at least to restore the
      procreative potential are available. Creation of embryos by IVF, oocyte donation
      and cryopreservation of mature or immature oocytes are potential issues, the
      advantages and limitations of which are discussed. Recently, ovarian tissue
      cryopreservation has spurred interest in the medical literature as well as in the
      lay press as a method for preservation and restoring fertility. Considering the
      available data and current state of knowledge, we want to stress that this
      methodology is still in an experimental phase and we would like to caution
      against unwarranted enthusiasm of physicians and patients. The medical
      information preceding the informed consent should mention the actual
      uncertainties of this method. Moreover, the imperative character of the offer and
      in particular for paediatric oncological patients, the force of the moral rules
      that define parental obligations towards children should not be ignored.

PMID- 12513852
TI  - Follitropin-beta administered by pen device has superior local tolerance compared
      with follitropin-alpha administered by conventional syringe.
AB  - A receiver- and assessor-blind, randomized, single-centre, crossover study was
      performed in 60 healthy women volunteers, to compare the local tolerance of two
      recombinant FSH preparations administered by a pen device (delivering 150 IU
      follitropin-beta) or by conventional syringe (delivering 150 IU follitropin
      alpha). Volunteers were randomized to one of two treatment sequences: pen device
      followed by conventional syringe, or the reverse. Each preparation was injected
      once, subcutaneously in the umbilical region and local tolerance reactions were
      assessed within 5 min, at 1 and 24 h after each administration. In addition,
      subjects were asked to rate the pain experienced during a period of 24 h after
      each injection by means of a visual analogue scale (VAS). At administration
      (within 5 min), severe to moderate pain was experienced in 70.0% of subjects
      injected by the conventional syringe, whereas only 21.7% of subjects treated with
      the pen device experienced pain. This difference was highly significant (P </=
      0.001). The overall pain score (VAS) was low but significantly lower in subjects
      treated with the pen device (P </= 0.01). In this study, follitropin-beta
      administered by the pen device was far less painful than follitropin-alpha
      administered by conventional syringe. The pen device is the first multiple-use
      device available for the self-administration of recombinant FSH (rFSH) during
      ovarian stimulation for assisted reproduction.

PMID- 12513853
TI  - Use of recombinant FSH and recombinant LH in multiple follicular stimulation for
      IVF: a preliminary study.
AB  - Twelve patients (17 cycles) who needed >3000 IU of recombinant FSH (rFSH) on
      previous follicular stimulation attempts for IVF using rFSH (group A) underwent
      further attempts (a total of 12 cycles) using rFSH supplemented with rLH from day
      7 of stimulation (group B). There was no significant difference in the total
      quantitative administration of rFSH (mean: 4759 versus 4800 IU rFSH), days of
      stimulation (14.0 versus 12.6), number of M2 oocytes per patient (3.76 versus
      4.17) or embryo morphology between group A and group B respectively. However,
      there was a significant increase in the incidence of fertilization (60.9 versus
      86.0%; P = 0.006) and clinical (ongoing) pregnancies (1 versus 6; P = 0.022). The
      higher incidence of fertilization increased the mean number of embryos
      transferred per patient, although in this small group the data was not
      significant (1.75 versus 2.71). This preliminary clinical trial suggests that in
      poor responders superimposing rLH upon a down-regulated cycle stimulated with
      rFSH improves relevant outcome data; and this preliminary trial has encouraged
      the need for a larger and more detailed study.

PMID- 12513854
TI  - Comparison of the effectiveness of recombinant and urinary FSH preparations in
      the achievement of follicular selection in chronic anovulation.
AB  - In order to compare the effectiveness of urinary and recombinant FSH (rFSH)
      preparations in achieving the threshold of follicular growth, stimulated cycles
      from patients with chronic anovulation, treated with a constant dose of FSH until
      the emergence of a selected follicle, were retrospectively analysed. Sixty-four
      cycles were performed using a similar starting dose of either urinary FSH (group
      1) or rFSH (group 2), which was kept constant up to the time of follicular
      selection, assessed on ultrasound (follicular diameter >10 mm). The results of
      this study showed that, while the number of selected follicles was similar, the
      mean daily FSH dose required to achieve the threshold of follicular selection was
      significantly lower in group 2 (70.4 +/- 3.4 IU/day) than in group 1 (86.5 +/- 4
      IU/day; P < 0.005). Furthermore, at the time of human chorionic gonadotrophin
      (HCG) administration, the total FSH dose was significantly lower in group 2 than
      in group 1, but plasma oestradiol values were equivalent. These data suggest that
      the higher effectiveness of rFSH preparations over urinary ones may be explained
      by a lower threshold dose required to achieve follicular selection.

PMID- 12513855
TI  - Influence of the dominant follicle on in-vitro maturation of human oocytes: a
      prospective non-randomized study.
AB  - The present study was designed to examine the influence of timing of aspiration
      and the influence of a dominant follicle on maturation and fertility potential of
      immature oocytes aspirated in unstimulated cycles. The study included 81
      regularly cycling women. In group I (n = 53), oocyte retrieval was scheduled the
      day after a follicle of 10 mm and an endometrium of at least 5 mm were observed.
      In group II (n = 28), aspiration was scheduled the day after observation of the
      same ultrasound criteria plus a detected increase (100%) in the level of
      oestradiol compared with the level on day 3. The maturation rate was
      significantly higher in group I compared with group II (107/184, 58.2% versus
      56/124, 45.2%, P < 0.05), whereas the rates of fertilization and cleavage did not
      differ between the two groups. The clinical pregnancy rate per aspiration was
      significantly higher in group I compared with group II (9/53, 17% versus 0/28,
      0%, P < 0.05). When comparing oocytes originating from the ovary with the
      dominant follicle (ipsilateral ovary) with oocytes originating from the ovary
      without a dominant follicle (contralateral ovary) an increased fertilization rate
      was observed in group I, and an increased maturation rate was observed in group
      II. When the data from the two groups were pooled, an increased maturation rate
      was observed in oocytes originating from the ipsilateral ovary compared with
      oocytes originating from the contralateral ovary. No difference was found with
      respect to rates of fertilization and cleavage rates when all oocytes originating
      from the ipsilateral ovary were compared with all oocytes originating from the
      contralateral ovary.

PMID- 12513856
TI  - Fertilization of mouse oocytes using somatic cells as male germ cells.
AB  - Female and male mouse somatic cells were injected into mouse F(1) oocytes. The
      cells used included cumulus cells (female) and muscle derived fibroblasts (male).
      The ability of the cells to fertilize oocytes and support embryonic development
      was examined. Following activation of the injected oocytes, two second polar
      bodies were extruded and two pronuclei were formed, one derived from the oocyte
      chromosomes and the other from the somatic cell chromosomes in a similar way to
      that observed following fertilization with secondary spermatocytes. Both second
      polar bodies contained DNA. The fertilization rates by cumulus cells were 10-29%.
      This was dependent on the artificial activation protocol and on the age of the
      oocytes. Older oocytes recovered 16-17 h after human chorionic gonadotrophin
      (HCG) injection were more likely to produce two second polar bodies and two
      pronuclei than young oocytes which were retrieved at 13-14 h after HCG injection
      (P < 0.01). The fertilization rates with fibroblasts were 29% using the most
      effective activation regime and aged oocytes. Most (80-90%) of the 'zygotes'
      produced by somatic cells cleaved to two cells in culture and ~50% reached the
      morula stage. However, the developmental competence of the embryos to reach
      blastocysts was limited. The present study demonstrates that mouse somatic cells
      undergo haploidization when injected into metaphase II oocytes, fertilize oocytes
      as diploid male germ cells and support preimplantation development to a degree.

PMID- 12513857
TI  - Morphology of spermatozoa used in IVF and ICSI from oligozoospermic men.
AB  - The purpose of this study was to determine morphology in human spermatozoa from
      men with oligozoospermia and correlate with the fertilization rate, embryo score
      and pregnancy rate after IVF and intracytoplasmic sperm injection (ICSI)
      respectively. The study group consisted of 125 couples where the male partner
      suffered from oligozoospermia. Fifty of these had IVF (group A). Seventy-five
      couples in whom ICSI had been performed made up group B. Sperm samples were
      assessed according to the WHO manual. For each male, morphology of spermatozoa
      was judged according to Kruger's strict criteria, WHO criteria and the
      teratozoospermia index (TZI). Oocyte monitoring was carried out according to a
      long down-regulation protocol using gonadotrophin-releasing hormone, recombinant
      FSH and human chorionic gonadotrophin. Embryos were transferred on day 2 after
      fertilization, with a maximum of three embryos. This study demonstrated no
      correlation between any of the morphological assessments of spermatozoa and the
      fertilization rate, embryo score and pregnancy rate, either after IVF or ICSI.
      Morphology in human spermatozoa according to Kruger's strict criteria, WHO
      criteria and the TZI had no predictive value for the outcome after either IVF or
      ICSI.

PMID- 12513858
TI  - ICSI and day 5 embryo transfers: higher implantation rates and lower rate of
      multiple pregnancy with prolonged culture.
AB  - This retrospective review study, carried out in a private IVF clinic, compared
      pregnancy and implantation rates with day 3 versus day 5 embryo transfers in a
      selected group of patients. Participants were patients who failed to achieve
      pregnancy in at least one previous attempt with embryo transfer on days 2 or 3,
      and had more than five oocytes fertilized. A total of 296 patients who had
      undergone day 3 (group A) transfers were compared with 154 who had undergone day
      5 transfers (group B). Interventions were intracytoplasmic sperm injection
      (ICSI), day 3 and day 5 embryo transfer. Outcome measures were pregnancy,
      implantation, multiple gestation and blastocyst formation rates. Overall, 86.4%
      of embryos were at the six- to eight-cell stage at 72 h and 30% developed to
      blastocyst by day 5. The mean number of embryos transferred was 4.0 on day 3 and
      3.0 on day 5. Pregnancy and implantation rates were 34.8 and 11.5% in group A,
      versus 45.3 and 18.5% in group B. Multiple gestation rate was 47.1% in group A
      and 28.5% in group B. Prolonging embryo culture in vitro to day 5 improved embryo
      selection and implantation rates. A significant decrease in high order gestations
      was achieved by reducing the number of embryos transferred, without compromising
      the pregnancy rates.

PMID- 12513860
TI  - Evolution of preimplantation genetic diagnosis in France.

PMID- 12513859
TI  - Expression of bcl(xs) and c-myc in atretic follicles of mouse ovary.
AB  - At birth, in the human female, one million follicles are present, out of which
      only 450 ovulate during the reproductive lifespan while the remainder of the
      99.9% follicles degenerate. It is therefore important to understand the
      regulation of follicular atresia. Immature mice injected with pregnant mare serum
      gonadotrophin (PMSG) were used as a model for follicular atresia. In this model,
      we demonstrated by various methods, including the TdT-mediated dUTP nick end
      labelling (TUNEL) technique, that granulosa cells in atretic follicles undergo
      apoptosis. In eukaryotic cells, apoptosis is regulated by genes such as bcl(2)
      and c-myc. Regulation of apoptosis in the ovary by these proteins/genes was
      studied using the mouse model. bcl(2) is anti-apoptotic; however, bcl(xs), a
      member of the bcl(2) family, is apoptotic. Immunohistochemical localization of
      bcl(xs) in the granulosa cells of atretic follicles suggested its role in
      follicular atresia. Expression of c-myc was studied by in-situ hybridization in
      the mouse follicular atresia model. In the atretic follicles, expression of c-myc
      in granulosa cells was observed. Thus our studies indicate that bcl(xs) regulates
      granulosa cell apoptosis, while c-myc may also play a role in cell death during
      follicular atresia.

PMID- 12513861
TI  - Impact of intracytoplasmic sperm injection on the activation and fertilization
      process of oocytes.
AB  - Intracytoplasmic sperm injection (ICSI) is used worldwide to treat preferentially
      severe cases of male factor infertility. In this review, data regarding the
      processes of oocyte activation and fertilization in non-assisted conception,
      conventional IVF and ICSI are discussed. The second messenger calcium shows a
      typical pattern after ICSI, which is different from that after subzonal
      insemination (SUZI), which is closer to the conditions of normal fertilization.
      The onset of calcium spikes is delayed. Sometimes a monophasic calcium pattern,
      in animals typical for parthenogenetic activation, is observed despite normal
      subsequent oocyte activation. Furthermore, the frequency of spikes is higher
      after SUZI, and only one phase instead of two is observed after ICSI for the
      second onset of calcium release. These alterations may be explained by the
      differences in oocyte activation after ICSI, since no oolemma-sperm contact is
      present. Sperm decondensation also follows another pattern after ICSI: as long as
      residuals of the acrosome are present on the sperm head, no sperm decondensation
      takes place at that site. Therefore, decondensation is delayed and pronucleus
      formation, especially that of the male pronucleus, takes longer after ICSI as
      compared with conventional IVF. Since studies have shown that gonosomes are
      located preferentially in the apical part of the sperm nucleus, this was proposed
      to be an explanation for a higher incidence of gonosomal aberrations in offspring
      after ICSI. However, other explanations, taking clinical data like the background
      risk of the parents into account, can also be offered for this phenomenon. These
      alternative theories are more likely to be associated with a slight instead of a
      frank increase in gonosomal aberrations. The inheritance of paternal
      mitochondrial DNA seems not to be a problem after ICSI, as shown by different
      studies. Mitochondrial DNA can be demonstrated in embryos after conventional IVF
      as after ICSI up to the blastocyst stage but not in children born after ICSI.
      Finally, lesion of the meiotic spindle by the ICSI procedure seems not to be a
      problem when data from different studies are taken into account. As assumed also
      at the beginning of the ICSI era, the meiotic spindle is almost always located in
      an area of < 90 degrees deviation from the polar body axis. Therefore, intrusion
      of the microinjection needle at the 90 degrees position might not endanger the
      spindle apparatus. To conclude, several studies using different approaches might
      show differences in the oocyte activation pattern, the 'choreography of
      fertilization' and pronucleus formation after ICSI. However, this different
      pattern does not necessarily mean that ICSI per se is a problem for embryonal
      development. The different pattern can be explained by the fact that ICSI uses
      another means of oocyte entry than the normal fertilization process. The clinical
      data of a high fertilization, cleavage and implantation rate, and especially the
      data from newborn babies, show that ICSI is a reliable procedure.

PMID- 12513862
TI  - Fertilization rate and preimplantation development after intracytoplasmic sperm
      injection.
AB  - Intracytoplasmic sperm injection (ICSI) is the treatment of choice in cases of
      male factor infertility. In the present review, all data from the literature
      regarding early fertlilization and preimplantation embryo development are
      analysed. ICSI seems to offer better fertilization rates than conventional IVF,
      even in the absence of a male factor and in prospective, randomized studies on
      sibling oocytes. Blastocyst formation is lower in ICSI than in IVF. This may be
      due to sublethal disturbances in oocyte architecture and function. Implantation
      and pregnancy rates, however, are similiar in ICSI and conventional IVF.
      Therefore, it can be concluded that ICSI offers a safe approach, as far as is
      known to date, for the treatment of male factor infertility. Embryo selection in
      cases of sublethal damage to oocytes seems to take place in the early
      preimplantation stages. Nor does the risk of monozygotic twinning, which was also
      proposed to be higher in ICSI compared with conventional IVF, seem to increase
      with this procedure.

PMID- 12513863
TI  - Luteal phase support.
AB  - Assisted reproductive techniques have become a routine treatment for infertility.
      The extended use of gonadotrophin-releasing hormone analogues in assisted
      reproductive techniques has made luteal phase support mandatory, as it has been
      clearly demonstrated that they alter luteal LH pulsatility. For luteal support,
      HCG administration, though effective, has a high risk of ovarian hyperstimulation
      syndrome. Progesterone continues to be the gold standard for supplementation.
      Vaginal progesterone represents a highly effective alternative to painful
      intramuscular injections. The vaginal route is mainly characterized by direct
      delivery of the progesterone to the endometrium, thus producing high levels at
      the target tissue and a very low incidence of side effects.

PMID- 12513864
TI  - British disciplinary or legal actions proliferate in IVF.

PMID- 12513865
TI  - Oocyte and follicle quality and success with IVF.

PMID- 12513866
TI  - Conception and pregnancy stirs legal action in France.

PMID- 12513867
TI  - Egg sharing: an NHS consultant's view.
AB  - Fertility services in the UK National Health Service are underfunded and subject
      to considerable regional variation despite the publication of national evidenced
      based guidelines commissioned by the Department of Health. Competition for
      funding within the NHS makes it unlikely that fertility will ever be fully
      funded. Novel and imaginative solutions are sought, of which some have already
      been rejected. Egg sharing could provide a means of increasing the availability
      of complex assisted conception techniques to a greater number of subfertile
      couples, who would otherwise be excluded. On the other hand, it would be
      understandable but unfortunate if healthcare providers view the success of egg
      sharing as an opportunity to shift the already limited funds to other competing
      specialties. Egg sharing is readily accepted by many UK couples and provides a
      dignified solution to two separate clinical problems, without reducing the
      donor's chances of conceiving or involving complex financial negotiations. Many
      couples are also comforted by the thought that even if their treatment is
      ultimately unsuccessful others have also been given a chance.

PMID- 12513868
TI  - Definitions of human fertilization and preimplantation growth revisited.
AB  - Assisted reproductive techniques and the science of embryology have advanced
      rapidly over the last decades. The fact that social and moral objectives vary
      from country to country has resulted in differences not only in legislation, but
      also in the definition of embryological terms. Among the latest additions to the
      field has been nuclear transfer technology, which has led to concerns about the
      possibilities of human cloning. These facts call for a review of gametogenesis
      and early embryogenesis. The aim of the present paper is to initiate a discussion
      on terminology with a view to reaching a consensus. As a starting point
      definitions are proposed for the most important terms.

PMID- 12513869
TI  - Regulating reproduction: the art of decision-making in ART.
AB  - Fertility treatment in the UK takes place within a strict regulatory framework
      that represents the outcome of legislative decisions aimed at protecting the
      interests of both patients and the public, whilst maximizing the acceptable
      reproductive options available to them. The role and responsibilities of the
      Human Fertilisation and Embryology Authority are described and illustrated in the
      context of the complementary domains of the lawmakers on the one hand and
      clinicians on the other. The constitution of the HFEA - its multidisciplinary
      membership, internal committee structure and the function of its officers - is
      characterized as a mechanism that ensures that relevant perspectives inform its
      decision-making whilst guarding against the charge of partiality. Through the
      Code of Practice it produces and the licensing system it operates, the HFEA both
      protects and supports good clinical decision-making within the ART community.

PMID- 12513870
TI  - Follitropin-alfa for ovarian stimulation during assisted reproduction treatment:
      a national collaborative study.
AB  - This prospective, observational study investigated the efficacy and tolerability
      of follitropin-alfa for ovarian stimulation in routine clinical practice. The
      study involved a large, unselected population of women. Stimulation parameters
      and treatment outcomes were documented for 767 patients who underwent a total of
      1098 cycles of follitropin-alfa according to the clinic's standard protocol.
      Stimulation lasted a median of 11 days and used a cumulative dosage of 28
      ampoules of 75 IU follitropin-alfa. Pituitary down-regulation was used in 81.2%
      of cycles, predominantly by the long protocol. The desired ovarian development
      was achieved in 99.5% of cycles and embryo transfer took place in 86.9% of
      cycles, with an average of 2.5 embryos transferred. The clinical pregnancy rate
      was 39.5% and the miscarriage rate was 12.2%. Ovarian hyperstimulation syndrome
      was observed in only 12 cycles (1.1%). In conclusion, follitropin-alfa is
      effective and well tolerated for ovarian stimulation during routine clinical
      practice.

PMID- 12513871
TI  - Inhibin A/B in HMG or recombinant FSH ovarian stimulation with cetrorelix
      medication.
AB  - The inhibins are valuable factors in the assessment of the quality of an ovarian
      stimulation cycle. In spite of good clinical results with recombinant FSH and
      multiple dose LHRH- antagonist (Cetrotide((R))) administration, there remains a
      theoretical concern that in cycles stimulated with recombinant FSH, devoid of any
      LH activity, not enough endogenous LH is available to guarantee good follicle
      maturation. A total of 287 serum samples from 41 patients was assessed: 20
      patients received ovarian stimulation with recombinant FSH, 21 patients with HMG
      and multiple dose Cetrotide administration. Inhibin A and B were measured on
      cycle days 2 and 6, the day of HCG administration, the day of embryo transfer as
      well as 7 and 14 days after the transfer. The two patient groups were similar
      with regard to age, amount of gonadotrophins required and number of follicles >18
      mm and 15-18 mm. Inhibin A and B concentrations were comparable throughout the
      stimulation, thus indicating the equality of ovarian stimulation with recombinant
      FSH/HMG and midcyclic antagonist administration. Higher inhibin B concentrations
      throughout the stimulation were correlated with a higher oocyte yield. The small
      number of pregnancies prevented assessment of the relationship between inhibin B
      values and pregnancy rate.

PMID- 12513872
TI  - Body mass index is inversely related to intrafollicular HCG concentrations,
      embryo quality and IVF outcome.
AB  - Decreased periovulatory human chorionic gonadotrophin (HCG) concentrations have
      been shown to be associated with diminished fertilization rates. This study
      evaluated if intra-follicular HCG concentration may be related to body mass in
      247 IVF patients using their own oocytes and 58 patients receiving donor oocytes,
      and evaluated if such a relationship might affect IVF outcome. A significant
      inverse correlation (r = -0.353, P < 0.001) was observed between the body mass
      index (BMI) and intra-follicular HCG concentration. The mean HCG concentrations
      were significantly decreased (P < 0.001) in patients with a BMI >30 kg/m(2)
      compared with patients with a BMI of 20-30 kg/m(2) or BMI <20 kg/m(2) (17.6
      versus 45.1 and 52.5%, respectively). The clinical pregnancy rates (P < 0.001)
      and embryo quality (P < 0.05) were significantly different for the three groups.
      In donor oocyte recipients, the pregnancy rate was significantly decreased (P <
      0.0001) for recipients with a BMI >25 kg/m(2) compared with those with a BMI from
      21-25 kg/m(2) and BMI <21 kg/m(2) (43.8 versus 72 and 76.5%, respectively). These
      data indicate that intra-follicular HCG concentration is inversely related to
      BMI, and may be related to a concurrent decrease in embryo quality and pregnancy
      rates.

PMID- 12513873
TI  - Maternal serum supplementation in culture medium benefits maturation of immature
      human oocytes.
AB  - This study compared the rates of maturation, fertilization, cleavage and
      pregnancy among oocytes matured in medium containing either human serum albumin
      (HSA) or maternal serum. Immature oocytes were obtained from 51 consecutive
      regularly cycling women <38 years of age. Immature oocytes were aspirated
      transvaginally on cycle day 8-9 after priming with FSH (Gonal-F 150 IU/day for 3
      days, initiated on day 3). Oocytes were matured in Dyrkningsmedie til IVM
      supplemented with recombinant FSH (rFSH) 0.075 IU/ml and HCG 0.5 IU/ml for 28-30
      h. In group I (n = 63 oocytes obtained from the first 23 cycles) the culture
      medium was supplemented with 2% (w/v) HSA. In group II (n = 74 oocytes obtained
      from the following 28 cycles) the medium was supplemented with 10% (v/v) heat
      inactivated maternal serum. Intracytoplasmic sperm injection (ICSI) was performed
      on all methaphase II oocytes. Significantly increased rates of maturation 47/74
      (63%) vs. 26/63 (41%) (P < 0.05), pregnancy 6/28 (21%) vs. 0/23 (0%) (P < 0.05)
      and implantation 6/20 (30%) vs. 0/15 (0%) (P < 0.05) were obtained from oocytes
      matured in culture medium with maternal serum supplementation compared with
      oocytes matured in medium supplemented with HSA. These results indicate that
      factors other than albumin in maternal serum play an important role in maturation
      and subsequent developmental capacity of human oocytes.

PMID- 12513874
TI  - Zona dissection by infrared laser: developmental consequences in the mouse,
      technical considerations, and controlled clinical trial.
AB  - Infrared laser systems are currently being marketed for application in clinical
      zona pellucida dissection. However, these systems have undergone only limited
      animal testing and minor clinical trials that lacked proper controls. Two of
      these systems have been evaluated in protocols that addressed potential
      detrimental effects on embryonic development in the mouse. Exaggerated large
      openings were made in the zona pellucida of 8-16 cell mouse embryos. Embryonic
      development and subsequent implantation and viability were assessed. A definite
      negative effect on these parameters was observed following the use of one of
      these systems. Following this animal trial, the second system was evaluated in a
      clinical trial for assisted hatching and embryo biopsy. Laser dissection was
      directly compared with the standard zona drilling using acidified Tyrode's
      solution. While no significant difference was evident between the two protocols,
      it was felt that laser dissection presented some problems in both consistency
      between operators and in the efficacy of subsequent manipulations such as
      blastomere biopsy and fragment removal. These results argue that laser zona
      dissection is far from a simple technique and should be carefully evaluated
      before any clinical application is made.

PMID- 12513875
TI  - Glucose metabolism of human morula and blastocyst-stage embryos and its
      relationship to viability after transfer.
AB  - The pregnancy rate and implantation rate following blastocyst transfer in the
      human have been reported to be high; however, it has remained necessary to
      transfer 2-3 blastocysts to achieve these rates. Morphological criteria are
      currently used to select blastocysts for transfer and have some limited
      correlation with ongoing viability. Glucose metabolism of 189 human morula to
      blastocyst stage embryos was analysed using a non-invasive ultramicrofluorescence
      technique to determine if this could be used to predict viability. There was a
      linear trend to increased glucose uptake with progression from the morula to the
      hatching/hatched blastocyst stage of development, whereas glycolytic activity did
      not vary. There was no consistent difference in glucose uptake or glycolytic
      activity for embryos at the various morphological stages on day 5 compared to day
      6 in vitro. Glucose uptake and glycolytic activity of the nine embryos positively
      identified as having implanted following transfer varied and were apparently not
      different from the values for embryos that failed to implant. In addition,
      viability was demonstrated to be compatible with high glycolytic activity, with
      four of nine implanted embryos having a glycolytic activity in the highest 15% of
      the population of embryos studied. Glucose uptake and glycolytic activity of male
      and female embryos did not appear to be different. Glucose metabolism cannot be
      used prospectively to select viable human morula or blastocyst stage embryos for
      transfer and it is also unlikely to be a useful tool to predict the sex of the
      embryo.

PMID- 12513876
TI  - Habitual complete molar pregnancy: a case report.
AB  - Gestational trophoblastic disease is rare in industrialized countries. Rarer
      still are recurrent or habitual molar pregnancies. A rare case of hydatidiform
      mole occurring seven times consecutively without a normal pregnancy in an
      Egyptian woman is presented. She was first seen with her first molar pregnancy in
      1994 at the age of 21 years. Subsequently, she had six consecutive molar
      pregnancies. The last was in October 1999; it was followed by a gestational
      trophoblastic disease. Each molar pregnancy was diagnosed ultrasonographically
      and confirmed by histopathological examination. Management of such patients is
      problematic especially when there is a desire for future childbearing.

PMID- 12513877
TI  - Ovarian differentiation and human embryo quality. 1. Molecular and morphogenetic
      homologies between oocytes and embryos in Drosophila, C. elegans, Xenopus and
      mammals.
AB  - Knowledge on the formation of oocytes and follicles in Drosophila, C. elegans and
      Xenopus, and the genetic regulation of polarities and embryo growth, has been
      related to comparable data in mammalian oocytes and embryos. Initially, details
      of the nature of the regulatory processes in the non-mammals are described, with
      considerable attention being paid to the role of individual genes and their
      specific functions. The molecular genetic aspects of these developmental
      processes are discussed in detail. Attention then turns to mammals, to identify,
      describe and evaluate their homologies with the lower animals and flies. Several
      of these homologies are described, including genes regulating primary ovarian
      failure and various aspects of early embryonic growth. The polarized distribution
      of genes in mammalian oocytes and embyros is discussed, together with the
      implications in the form of differentiation in the early embryo. Morphogenetic
      systems operative during follicle maturation, fertilization and cleavage are
      described and related to similar processes in lower forms. These events include
      ooplasmic and pronuclear rotations, the form of ooplasmic inheritance in early
      blastomeres and the establishment of embryonic axes. Models of early mammalian
      development are considered.

PMID- 12513878
TI  - U.S. taxpayer dollars to support limited stem cell research.

PMID- 12513880
TI  - Embryo 'adoption': a limited option.

PMID- 12513879
TI  - Comment: Could stem cells be derived from cryopreserved embryos? 

PMID- 12513881
TI  - Celebrating preimplantation genetic diagnosis of p53 mutations in Li-Fraumeni
      syndrome.

PMID- 12513882
TI  - Preimplantation genetic diagnosis for familial cancer.

PMID- 12513883
TI  - Donor eggs and brother's sperm: are the ethical concerns real? 

PMID- 12513884
TI  - A preliminary study on the possible role for luteinizing hormone in androgen
      independent growth of prostate.
AB  - The recent observation that LH receptors are found in the prostate and that LH
      can execute a mitogenic role in addition to its well documented role in
      stimulation of steroidogenesis prompted the evaluation of the role of LH in
      regulation of prostate growth. The results obtained in the present study reveal
      the presence of LH receptor transcript as well as receptor protein in the rat
      prostate. The LH receptor appears to be localized in the non-secretory epithelial
      cells of the prostate as assessed by I(125) LH binding and immunofluorescence.
      Addition of HCG to purified prostate cells resulted in an increase in
      bromodeoxyuridine incorporation only in the non-secretory epithelial cells. Using
      a castrated adult rat model system, it has also been observed that LH receptor is
      regulated by LH itself, and that LH also regulates protein synthesis in the
      prostate. In addition, it has been possible to demonstrate the presence of LH
      receptor in the prostate from cases of human benign prostate hyperplasia. These
      results suggest a possible role for LH in the regulation of prostate growth.

PMID- 12513885
TI  - Preoperative reduction of uterine fibroids in only 16 days by administration of a
      gonadotrophin-releasing hormone antagonist (Cetrotide).
AB  - Ten premenopausal women with symptomatic uterine fibroids confirmed by magnetic
      resonance imaging (MRI) were treated with four injections (s.c.) of 3 mg of the
      gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix every 4 days,
      starting on the first day of cycle. On every fourth day, blood samples were drawn
      for the measurement of gonadotrophins and sex steroids. On the 17th day of
      treatment after a final MRI control, myomectomy was performed laparotomically,
      laparoscopically or hysteroscopically. All patients showed a deep and sustained
      suppression of gonadotrophins and sex steroids over the treatment time. In three
      patients, no change or even an increase in uterine fibroids volume was observed
      according to MRI, and in one patient MRI did not allow a reliable interpretation.
      However, six patients showed a mean reduction of 31% in fibroid size after only
      16 days of hormonal treatment. In nine patients laparoscopic or hysteroscopic
      myomectomy could be performed, while laparotomy was necessary only in one non
      responder. Preparation of the cleavage plane during surgery was easy and blood
      loss was minimal. Patient compliance was excellent. No side-effects occurred. The
      GnRH antagonist Cetrotide(R), acting as an intermediate depot preparation at a
      dose of 3 mg, opens up a new avenue for preoperative short term treatment in a
      subgroup of patients with uterine fibroids, minimizing treatment time and patient
      discomfort.

PMID- 12513886
TI  - Donor eggs and brother's sperm: creating genetic likeness in the conceptus of an
      unmarried menopausal woman.
AB  - A 51-year old woman desiring to have a child with genetic similarity to herself
      chose to undergo egg donation using her brother's spermatozoa. Following careful
      screening of all participants, in-vitro fertilization and embryo transfer was
      accomplished. The patient failed to become pregnant, but a subsequent embryo
      transfer using cryopreserved embryos obtained during the initial attempt
      successfully resulted in a singleton pregnancy. Although rarely requested, under
      certain circumstances, the choice of a brother as a designated sperm donor, may
      be reasonable, allowing a woman who would otherwise have no genetic likeness to
      the child, a chance for motherhood.

PMID- 12513887
TI  - Reducing the time of co-incubation of gametes in human in-vitro fertilization has
      no beneficial effects.
AB  - Reports concerning the benefit of reducing the co-incubation time of gametes in
      connection with IVF have been conflicting. The present randomized study was
      undertaken to determine whether a reduced co-incubation time would improve the
      embryo development and consequently the pregnancy and implantation rates. Oocytes
      from 87 patients were collected and half the oocytes from each patient (n = 488,
      group A) were randomized to 2 h incubation and the other half (n = 504, group B)
      to overnight incubation. The oocytes were then cultured according to our standard
      procedure. Significant difference (P = 0.02) was observed between the two groups
      regarding fertilization rate and polyspermy (group A 72.5%, 3% and group B 80.5%,
      6% respectively). However, no difference was observed in further development and
      morphology of the embryos. The two embryos with the best morphological score were
      selected for transfer. No significant difference was found between the different
      transfer groups regarding positive serum HCG and implantation rate. CONCLUSION:
      The present results and results from previously published studies indicate that
      the most important factor in connection with the culture method currently used is
      the amount of sperm added for co-incubation. This should be optimized to reduce
      the concentration of harmful sperm waste products and create optimal culture
      conditions.

PMID- 12513888
TI  - Simplified technique for differential staining of inner cell mass and
      trophectoderm cells of mouse and bovine blastocysts.
AB  - Histological staining and counting of blastocyst inner cell mass (ICM) and
      trophectoderm (TE) cells differentially with chromatin-specific dyes is a more
      accurate indicator of cultured blastocyst quality and normality than total cell
      number assessment. The aim of this study was to test the effectiveness of a
      simplified method of chemically-defined differential blastocyst staining. The TE
      of cultured mouse and bovine blastocysts of different developmental stages was
      stained when blastocysts were treated with a permeabilizing solution containing
      the ionic detergent Triton X-100 and the fluorochrome propidium iodide.
      Blastocysts were then incubated in a second solution containing 100% ethanol (for
      fixation) and the secondary fluorochrome bisbenzimide. Fixed and stained whole
      blastocysts were mounted and assessed for cell number using ultraviolet
      fluorescent microscopy. Using this method, in-vitro cultured mouse blastocysts
      (day 4.5) were shown to have an ICM:TE ratio of 1:2.63 with an average total cell
      count of 75.3 +/- 3. While day 7 and 8 in-vitro produced bovine blastocysts were
      shown to have an ICM:TE ratio of 1:3.42 and 1:3.36 with an average total cell
      count of 151.3 +/- 5.48 and 217.8 +/- 8.75 respectively. Blastocyst staining
      patterns indicate that this modified technique represents a simple and reliable
      alternative to current bichromatic blastocyst staining techniques for the
      differential assessment of cell numbers and may be useful for the assessment of
      blastocysts derived from in-vitro maturation, novel culture systems and advanced
      reproductive technologies such as cloning.

PMID- 12513889
TI  - Placental transfer of cotinine at 12-17 weeks of gestation and at term in heavy
      smokers.
AB  - The objective of this study was to compare the placental transfer of cotinine
      from maternal to fetal circulation in heavy chronic smokers during the second
      trimester of pregnancy and at term. Maternal and fetal cotinine concentrations
      were evaluated in 26 women requesting surgical termination for psychosocial
      reasons at 12-17 weeks gestation and 26 women with uncomplicated pregnancies at
      37-40 weeks gestation, and delivered vaginally. Cotinine concentrations were
      measured by radioimmunoassay. At 12-17 weeks, the median cotinine concentration
      was significantly (P = 0.009) lower in fetal than in maternal serum. At term
      fetal and maternal cotinine concentrations were similar. The feto-maternal ratio
      was significantly (P < 0.001) lower in second trimester pregnancies than in term
      pregnancies. In both groups, positive linear correlations were found between
      maternal and fetal serum cotinine concentration and between maternal serum
      cotinine concentration and the number of cigarettes smoked per day. These data
      indicate that placental cotinine transfer increases with advancing gestation.
      This may be secondary to increased placental permeability in the third trimester,
      which could be linked to progressive placental damage in heavy chronic smokers.

PMID- 12513890
TI  - Family planning needs: new opportunities, emergency contraception and other new
      technologies.
AB  - Modern contraception is considered to be one the major advances of the 20th
      century. Yet, as the next century begins, it is estimated that there is still a
      largely unmet need for contraception, with millions of couples worldwide who
      express a wish to limit the number of their children but do not use or are not
      satisfied with their contraceptive method. While the reasons are numerous, it is
      clear that there is a need for improved and new methods which are easier to use,
      under the user's control, with fewer side-effects and responding to the needs of
      different groups of users, including men. To respond to this need, current
      contraceptive research and development efforts focus on five main areas:
      emergency post-coital methods, user-controlled long-acting methods, dual
      protection methods against both pregnancy and sexually transmitted infections,
      methods for men, and methods with fewer side-effects including some that are more
      targeted to specific reproductive biological events. A number of leads are
      presented which are at various stages of development. Concluding remarks stress
      the numerous challenges of contraceptive development, not the least of which is
      the vision required of what the needs of future generations will be, since it
      takes 10-15 years to bring a new contraceptive to the market. More fundamentally,
      overall progress towards reducing the unmet need for contraception will depend on
      the status of women, specifically their decision-making power, and access to
      education and income.

PMID- 12513891
TI  - Differences in the practice of egg donation are a result of local culture and
      historical precedent.

PMID- 12513893
TI  - Guidance for egg sharing arrangements: redefining the limits of information
      giving in donor assisted conception.

PMID- 12513892
TI  - Oocyte donation: who should give? 

PMID- 12513894
TI  - Rebuttal: interooplasmic transfers in humans.

PMID- 12513896
TI  - Infertility coverage in the USA: a yes and no proposition.

PMID- 12513895
TI  - Induction of follicular growth and ovulation with urinary and recombinant
      gonadotrophins.
AB  - Gonadotrophins have been used since the 1930s. By the 1990s, a pure biological
      extract of FSH was obtained. The increase in the demand for new assisted
      reproduction techniques led to the creation of recombinant FSH, 99% pure and
      highly consistent between batches, with no LH activity, and a high specific
      activity. In gonadotrophin protocols, follicular growth can be monitored with
      regular ultrasounds and/or hormonal testing, mainly oestradiol in the follicular
      phase. In assisted reproduction the adoption of ovulation induction strategies
      with GnRH analogues, control the endogenous secretion of LH, avoiding
      cancellations due to an early LH surge, and premature ovulation. Depending on the
      moment when pituitary suppression starts, there are short, ultra-short and long
      protocols The use of long protocols not only increases pregnancies and live
      births, it also allows an easier programming and simplifies IVF treatments.
      Ovarian stimulation entails some risks such as ovarian hyperstimulation syndrome
      and multiple pregnancies that can be avoided in many cases with an accurate
      prediction and an active prevention.

PMID- 12513897
TI  - Choosing sex of offspring: concentrating human X- and Y-bearing spermatozoa.

PMID- 12513898
TI  - More consequences of the death of a volunteer in a U.S. clinical trial.

PMID- 12513899
TI  - Fatal lactic acidosis associated with antiretroviral therapy.

PMID- 12513900
TI  - Increasing hepatitis B vaccination among young African-American men who have sex
      with men: simple answers and difficult solutions.
AB  - Using a bar-based sample, we identified factors associated with hepatitis B virus
      (HBV) vaccination among young African American men who have sex with men (MSM).
      The mean (+/- standard deviation [SD]) age of the 170 participants was 26 +/- 6.5
      years. Nearly 40% reported at least one dose of vaccine; the remainder were
      completely unvaccinated. Approximately 22% (37) reported having never heard of
      HBV. Less than 7% of participants reported using condoms the majority of the time
      during oral intercourse within the past 3 months, and approximately 50% reported
      using condoms the majority of the time during anal intercourse within the past 3
      months. In multivariable analysis, variables associated with vaccination were
      younger age (odds ratio [OR], 0.44 per 10-year increase in age; 95% confidence
      interval [CI]: 0.21-0.93, p = 0.032), higher educational attainment (OR, 4.6; 95%
      CI: 1.17-12.59, p = 0.003), homosexual as opposed to bisexual behavior (OR, 0.15;
      95% CI: 0.06-0.41, p = 0.0001), and recent visits to a health care provider (OR,
      4.31; 95% CI: 2.08-8.94, p = 0.0001). Our findings underscore the need to reach
      MSM for HBV vaccination. Innovative approaches are necessary to ensure the
      prevention of infection, transmission and disease among individuals with limited
      education, bisexual MSM, and men who have limited access to health care.

PMID- 12513901
TI  - Directly administered antiretroviral therapy in the treatment of HIV infection:
      benefit or burden?
AB  - While combination antiretroviral treatment has had a profound impact on the
      morbidity and mortality of human immunodeficiency virus (HIV) infection, the
      adherence demands of this therapy are high and failure to maintain viral
      suppression is common. Directly administered antiretroviral therapy (DAART) has
      garnered attention recently as a strategy to improve medication adherence and
      clinical outcomes in HIV-infected individuals. This review is intended to provide
      an update on the use of DAART and the challenges posed by this strategy, explore
      settings in which DAART may be used, discuss the role of antiretroviral regimens
      with improved pharmacokinetic features, and propose future directions for DAART
      strategies. DAART is modeled on directly observed therapy (DOT) for the treatment
      of tuberculosis. However, differences in curability, medication dosing frequency,
      duration of treatment, and the biologic dynamics of infection, pose unique
      challenges to DAART strategies. Numerous settings have been proposed for DAART,
      including community based outreach programs, prisons, long-term care facilities,
      substance abuse treatment sites, and resource-poor countries. Experience with
      DAART to date has been limited to pilot studies or retrospective comparisons. The
      prospect of simplified, once-daily antiretroviral therapy holds promise for
      DAART. However, improvements in antiretroviral therapy may also improve outcomes
      in patients taking therapy on a self-administered basis. Randomized controlled
      trials of DAART are needed before this strategy can be embraced in any setting.
      In future studies it will be important to compare DAART with self-administered
      therapy in terms of initial virologic and immunologic responses, durability of
      responses, the development of antiretroviral resistance, and cost effectiveness.

PMID- 12513902
TI  - Desired elements of HIV testing services: test recipient perspectives.
AB  - Thematic analysis of transcripts from interviews with a purposive sample of 39
      voluntary human immunodeficiency virus (HIV) test recipients in Ontario (selected
      on the basis of HIV serostatus, risk behaviors, region of residence, gender, and
      testing format) was used to identify elements of HIV testing services of concern
      to test recipients. Colleague review was used to ensure dependability of
      findings, and emergent themes were compared with the existing literature on
      patient satisfaction. Data analysis identified a comprehensive set of 28 service
      elements, including components related to access and availability (convenience,
      physical accessibility, familiarity), structure of the service (privacy, and
      characteristics of the venue, session, and test provider), technical and medical
      aspects of the testing process (including blood-taking, file maintenance,
      obtaining informed consent, waiting period, and manner of result provision), and
      both cognitive and socioemotional aspects of the interpersonal process (including
      decision-making support, personalized risk information, receipt of appropriate
      emotional support, and service referrals). Results suggest that information on,
      and training in, counseling skills for both physician and nonphysician test
      counselors is important in the provision of quality testing services. Results
      also suggest that test recipients would appreciate choice in testing service
      options, and within the test session, individualized information, and counseling.

PMID- 12513903
TI  - Assessment of emergency department health care professionals' behaviors regarding
      HIV testing and referral for patients with STDs.
AB  - The objective of this study was to evaluate human immunodeficiency virus (HIV)
      counseling, testing, and referral practices of emergency department health care
      professionals (i.e., medical doctors [MD], physician assistants [PA], nurse
      practitioners [NP], and registered nurses [RN]) for patients presenting with
      other sexually transmitted diseases (STD). All health care professionals from 10
      emergency departments in a northeastern county were asked to complete an
      anonymous survey. The surveys were returned by 154 (41%) health care
      professionals (RN = 99, NP = 5, PA = 7, MD = 39, other = 4). The average years in
      practice were 11. Only 7% of respondents were certified to provide state mandated
      HIV pretest counseling (certification not required for MD). Respondents reported
      caring for an average of 13 patients per week with suspected STD. Fifty-five
      percent of respondents reported that they always or usually warn STD patients of
      their HIV risk, yet only 10% always or usually encouraged these patients to
      consent to HIV testing in their emergency department (RN = 7%, NP = 25%, PA = 0%,
      MD = 16%). Reasons for not offering HIV testing in their emergency department
      were follow-up concerns (51%), not certified to provide pretest/posttest
      counseling (45%), and too time consuming (19%). Twenty-seven percent of
      respondents indicated HIV testing was not available in their emergency department
      despite all hospital laboratories reporting HIV testing capability. Ninety-three
      percent of respondents were aware that confidential testing sites were available,
      but only 35% always or usually referred patients not tested in the emergency
      department elsewhere for testing. Emergency department health care professionals
      frequently fail to provide HIV counseling, testing, and/or referral for patients
      with suspected STD.

PMID- 12513904
TI  - Determinants of longer time from HIV result to enrollment in publicly funded care
      and treatment in California by race/ethnicity and behavioral risk.
AB  - The Early Intervention Program (EIP) is California's publicly funded human
      immunodeficiency virus (HIV) care and treatment program with 30 sites throughout
      the state. Our objective for this study was to examine the number of days from
      first HIV-positive result until enrollment into EIP by race/ethnicity, behavioral
      risk, and other characteristics, with data from clients who enrolled in an EIP
      site after the availability of highly active antiretroviral therapies. For Model
      I, logistic regression distinguished clients diagnosed with HIV and enrolled in
      EIP on the same day (0 days) from those with values of 1+ days; linear regression
      was then used on the log transformation of days for the majority of clients not
      diagnosed and enrolled on the same day. For Model II, logistic regression was
      used to identify client characteristics related to enrollment in EIP over 6 weeks
      from the date of HIV diagnosis. We found that Latinos were more likely than
      whites to enroll in EIP on the day they were diagnosed with HIV. For clients not
      diagnosed and enrolled in EIP on the same day, no differences across racial and
      ethnic groups were found for days until enrollment in HIV care and treatment.
      However, clients with a history of injection drug use took longer from the day
      they were diagnosed with HIV to enroll in EIP. The California EIP represents a
      model for programs seeking equity in access to HIV care and treatment across
      racial and ethnic groups. Getting injectors into timely HIV care and treatment
      represents a challenge.

PMID- 12513906
TI  - The natural alliance between type I interferon and dendritic cells and its role
      in linking innate and adaptive immunity.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) and
      thus play a pivotal role in induction of the immune response. Recent studies in
      both human and mouse models have shown that type I IFN, cytokines originally
      characterized for their antiviral activity and exerting multiple biologic
      effects, efficiently promote the differentiation and activation of DCs. These
      observations, together with the findings that DCs can express biologically
      relevant levels of type I interferon (IFN) and, in particular, that high amounts
      of these cytokines are released by specialized DC precursors (i.e., plasmacytoid
      DCs) in response to viral infections, strongly suggest the existence of a natural
      alliance between type I IFN and DCs, which is instrumental in ensuring an
      efficient immune response to both infectious agents and tumors. Further recent
      knowledge on the interactions between type I IFN and DCs emphasizes the
      importance of these cytokines in linking innate and adaptive immunity and may
      lead to new perspectives in their use as vaccine adjuvants as well as in
      strategies for the development of DC-based vaccines.

PMID- 12513907
TI  - Humoral immune response and protection from viral infection in mice vaccinated
      with inactivated MHV-68: effects of type I interferon.
AB  - Infection of mice by murine gammaherpesvirus 68 (MHV-68) represents a suitable
      animal model in which to investigate the immune response against
      gammaherpesviruses and to test the efficacy of vaccination strategies. In this
      study, we evaluated the efficacy of heat-inactivated MHV-68 as a vaccine as well
      as the adjuvant activity of type I interferon (IFN-I) administered together with
      the vaccine. Mice vaccinated with inactivated MHV-68 and subsequently infected
      with the virus exhibited a significant augmentation of the virus-specific humoral
      immune response and a considerable inhibition of MHV-68 acute replication in the
      lungs compared with unvaccinated control mice. The coadministration of IFN-I with
      inactivated MHV-68 significantly enhanced the humoral immune response elicited by
      the vaccine by stimulating the production of virus-specific IgG2 antibodies but
      did not significantly enhance protection from viral challenge. We conclude that
      IFN-I, recently shown to exhibit a powerful adjuvant activity to a poorly
      immunogenic subunit vaccine in mice, can also enhance the humoral immune response
      when used as adjuvant of an inactivated viral vaccine, even though this effect is
      less marked as a result of the strong immune response elicited by the inactivated
      virus alone, which may also involve the contribution of endogenous IFN.

PMID- 12513908
TI  - Direct evidence that IFN-beta functions as a tumor-suppressor protein.
AB  - Interferon-beta (IFN-beta) induces aberrant cell cycle progression as well as
      cytotoxicity and apoptosis. However, the relationship between the cell cycle
      alteration and the induction of cytotoxicity/apoptosis is unknown. Here, we
      report the first demonstration that the IFN-beta-induced direct
      cytotoxic/apoptotic effect can be separated functionally from its cell cycle
      effect. By using lentiviral transduction, we generated human tumor cells that
      stably expressed IFN-beta and were resistant to its direct cytotoxic/apoptotic
      effect. Despite this resistance to apoptosis, these cells showed significant S
      phase accumulation as measured by both FACS analyses and bromodeoxyuridine (BrdU)
      incorporation. Although the cells proliferated in the presence of high levels of
      IFN-beta, they had lost their tumorigenicity in mice. A portion of these cells
      was observed to undergo a tumor cell-specific senescence. Therefore, our study
      revealed a direct tumor-suppressor function of IFN-beta. This tumor-suppressor
      function was independent of IFN-beta-induced direct cytotoxic effect. It was also
      distinct from the IFN-beta-induced immunologic antitumor response, an indirect
      effect of IFN-beta. We conclude that the antiproliferative effect on human tumor
      cells is the collective activities of the direct cytotoxic/apoptotic effect, the
      cell cycle alteration that occurs as predominantly S phase accumulation, and less
      frequently other cell cycle effects, such as G(1) arrest, and the promotion of
      tumor cells into a senescent-like state.

PMID- 12513909
TI  - Comparison of interleukin-22 and interleukin-10 soluble receptor complexes.
AB  - Interleukin-22 (IL-22) is a cellular homolog of IL-10 that stimulates the
      production of acute-phase reactants. IL-22 and IL-10 require different ligand
      specific receptor chains (IL-22R and IL-10R1) but share a second receptor chain
      (IL-10R2) to initiate cellular responses. The quaternary structures and the
      ability of IL-22 and IL-10 to engage soluble (s) IL-10R1, IL-22R, IL-10R2
      receptor chains were analyzed using size exclusion chromatography and surface
      plasmon resonance techniques. In contrast to IL-10, which is a homodimer, IL-22
      is a monomer in solution that forms a 1:1 interaction with sIL-22R. Kinetic
      binding data reveal sIL-22R and sIL-10R1 exhibit specific nanomolar binding
      constants for IL-22 (k(on)/k(off) = 14.9 nM) and a monomeric isomer of IL-10 (IL
      10M1) (k(on)/k(off) = 0.7 nM), respectively. In contrast, IL-10R2 exhibits
      essentially no affinity for IL-22 (K(eq) approximately 1 mM) or IL-10M1 (K(eq)
      approximately 2 mM) alone but displays a substantial increase in affinity for the
      IL-10/sIL-10R1 (K(eq) approximately 350 microM) and IL-22/sIL-22R (K(eq)
      approximately 45 microM) complexes. Three-dimensional models of IL-22 and IL-10
      receptor complexes suggest two receptor residues (Gly-44 and Arg-96) are largely
      responsible for the marked differences in ligand affinity observed for sIL-10R1
      and sIL-22R vs. sIL-10R2.

PMID- 12513910
TI  - The mouse interferon-inducible gene Ifi204 product interacts with the Tpr
      protein, a component of the nuclear pore complex.
AB  - We have used yeast two-hybrid screening to isolate cDNA-encoding proteins
      interacting with the protein encoded by the interferon (IFN)-inducible gene
      Ifi204. Four independent overlapping clones were isolated from an NIH3T3 cDNA
      library. The largest clone encoded a protein (1203 amino acids in length) sharing
      94% identity with the C-terminal portion of the human translocated promoter
      region (Tpr) protein. Northern blot analysis revealed a 7.5-kilobase mRNA present
      in both mouse and human cell lines. In addition, in vivo interaction was
      demonstrated by coimmunoprecipitation experiments. Anti-Tpr polyclonal
      monospecific antibodies (Ab) used for immunofluorescence staining labeled the
      nuclear envelope (NE) in a punctate pattern characteristic of nucleoporins and
      also yielded staining throughout the nuclear interior. The intranuclear Tpr
      occurred in apparently discrete foci. When superimposed on optical sections
      obtained with anti-p204 Abs, these colocalized, with the sole exception of the
      nucleolar compartment stained by the anti-p204 Abs only. Although the specific
      function of Tpr is not defined, it appears to mediate p204 translocation from the
      cytoplasmic to the nuclear compartment following IFN treatment.

PMID- 12513911
TI  - Isolation and characterization of chicken interleukin-17 cDNA.
AB  - Interleukin-17 (IL-17) is a proinflammatory cytokine produced by activated T
      cells. A 917-bp cDNA encoding the IL-17 gene was isolated from our EST cDNA
      library prepared from intestinal intraepithelial lymphocytes (IELs) of Eimeria
      infected chickens. It contained a 507-bp open reading frame (ORF) predicted to
      encode a protein of 169 amino acids (aa) with a molecular mass of 18.9 kDa, a 27
      residue NH(2)-terminal signal peptide, a single potential N-linked glycosylation
      site, and 6 cysteine residues conserved with mammalian IL-17. Chicken IL-17 (chIL
      17) shared 37%-46% amino acid sequence identity to the previously described
      mammalian homologs and also was homologous to the ORF 13 of Herpesvirus saimiri
      (HVS 13). By Northern blot analysis, IL-17 transcripts were identified in a
      reticuloendotheliosis virus (REV)-transformed chicken lymphoblast cell line
      (CU205) and conconavalin A (ConA)-stimulated splenic lymphocytes but not other
      chicken cell lines or normal tissues. Conditioned medium from COS-7 cells
      transfected with ChIL-17 cDNA induced IL-6 production by chicken embryonic
      fibroblasts, suggesting a functional role for the cytokine in avian immunity.

PMID- 12513912
TI  - Elevated serum levels of interleukin-8 in advanced non-small cell lung cancer
      patients: relationship with prognosis.
AB  - Interleukin-8 (IL-8) is a pleiotropic cytokine that has also been shown to exert
      effects relevant to cancer growth and progression. Cancer progression is believed
      to be contributed to by the ability of this cytokine to promote angiogenesis and
      mitogenic effects. As IL-8 production at the tumor site may determine elevated
      serum levels of this cytokine because of hematogenous leakage, it is conceivable
      that patients with high IL-8 serum levels may have tumors actively producing this
      cytokine. The aim of this study was, therefore, to assess IL-8 serum levels in 60
      non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and to
      correlate them with prognosis. IL-8 serum levels were found to be significantly
      elevated in cancer patients with respect to controls. Moreover, IL-8 serum levels
      were shown to be significantly increased in stage IV patients compared with stage
      III patients. When basal IL-8 serum levels in cancer patients were analyzed
      according to response to chemotherapy, responders were shown to have
      significantly lower IL-8 serum levels than nonresponders. On univariate analysis,
      the IL-8 serum level was included among the variables capable of affecting both
      overall survival (OS) and time to treatment failure (TTF). However, multivariate
      analysis failed to demonstrate an independent prognostic significance for IL-8
      serum levels. In conclusion, this study showed that IL-8 serum levels were
      elevated in advanced NSCLC patients and correlated with both OS and TTF, but they
      were shown not to be an independent prognostic factor.

PMID- 12513913
TI  - Endogenous interleukin-4 downregulates the type 1 CD4 T cell-mediated immune
      response induced by intramuscular DNA immunization.
AB  - Intramuscular (i.m.) administration of eukaryotic plasmid vectors containing
      foreign genes is a general immunization strategy capable of inducing protective
      type 1 immune responses against viral, bacterial, fungal, and parasitic
      infections. We have described that immunization with a plasmid containing a gene
      encoding a parasite antigen elicits specific type 1 protective immune responses
      against experimental infection with the human protozoan parasite Trypanosoma
      cruzi. However, we had evidence suggesting that DNA immunization concomitantly
      activated specific type 2 immune responses. To determine precisely the influence
      of the type 2 cytokine interleukin-4 (IL-4) during DNA immunization, we compared
      the immune responses of genetically modified IL-4-deficient or wild-type (wt)
      BALB/c mice. IL-4-deficient mice had a significantly lower ratio of specific
      serum IgG1/IgG2a, and on in vitro restimulation with antigen, their spleen cells
      secreted significantly higher amounts of interferon-gamma (IFN-gamma). In
      contrast, absence of IL-4 did not affect total serum antibody response, T cell
      proliferative responses, or activation of IFN-gamma-producing CD8(+) T cells. Our
      results suggested that in contrast to conventional adjuvants, such as alum and
      complete Freund's adjuvant, specific IgG1 in DNA-immunized BALB/c mice was highly
      dependent on IL-4. To our knowledge, our study provides the first evidence that
      endogenous IL-4 selectively downregulates the type 1 CD4(+) T cell-mediated
      immune response induced by i.m. genetic immunization, a fact that may have
      implications for the design of certain DNA vaccines.

PMID- 12513914
TI  - Lack of antitumor activity and intolerance of interleukin-4 in patients with
      advanced HIV disease and Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS), the most common malignancy associated with HIV infection,
      is caused by the Kaposi sarcoma herpesvirus (KSHV). Exacerbations of KSHV are
      associated with increased human interleukin-6 (HuIL-6), and elevated IL-6 could
      be related to the development of KS. IL-4, a cytokine with pleiotropic effects,
      suppresses IL-6 in vivo and modestly inhibits AIDS-KS-derived cells in vitro.
      Suppression of IL-6 by exogenous IL-4 could result in antitumor activity. We
      report the results of a clinical trial to test this hypothesis. A phase I/II dose
      escalation safety, tolerance, and efficacy trial was conducted in patients with
      biopsy-proven AIDS-related KS, at two university medical centers. Patients were
      scheduled to receive IL-4 (0.5, 1.5, 3.0, or 4.0 microg/kg/day) administered
      subcutaneously (s.c.) in sequential cohorts. Patients were continued on study as
      long as the drug was tolerated or the disease progressed. Patients were followed
      for antitumor activity, effects on viral replication, immune status, and clinical
      and laboratory toxicity. Seventeen patients were enrolled at two sites over a 21
      month period. There were 15 males and 2 females, and 1 patient was Hispanic. All
      patients had a Karnofsky score >70. Patients enrolled only into the two lower
      dose cohorts (0.5 and 1.5 microg/kg/day). Both groups had similar baseline
      characteristics. The median time on treatment was only 7.4 and 8.4 weeks for the
      0.5 and 1.5 microg/kg/day dose levels, respectively. There was significant
      neutropenia, with 6 patients having grade 3 or greater toxicity requiring
      granulocyte colony-stimulating factor (G-CSF). Three patients on a dose of 1.5
      microg/kg/day stopped treatment due to protocol-defined toxicity. There were no
      appreciable effects on CD4/CD8 counts. HIV viral RNA did not significantly change
      over time. However, in several people, it appeared to decline with treatment and
      rebound with discontinuation of treatment. Corresponding changes were noted in
      the HIV immunocomplex dissociated (ICD) p24 antigen. One patient had a partial
      response, 11 patients had stable disease, and 5 patients had disease progression
      during the short period of treatment. The maximum tolerated dose for IL-4 in
      patients with advanced AIDS-related KS is 1.5 microg/kg/day. At this dose level,
      IL-4 is poorly tolerated and is not an effective KS treatment. Treatment of the
      majority of patients is discontinued because of drug-related toxicity or because
      of disease progression. Future studies of IL-4 should be confined to studies of
      cytokine manipulation of the underlying HIV infection, as there appears to be
      little antitumor activity.

PMID- 12513915
TI  - The new medicine.

PMID- 12513916
TI  - Wavelength, frequency, and color: absolute or relative concepts?
AB  - OBJECTIVE: The purpose of the present study is to call attention to well
      established concepts in optics, which, however, are not necessarily known by
      medical laser users but may be important for interpretation of some data.
      BACKGROUND DATA: In reviewing some aspects of the physical concepts of
      wavelength, frequency, photon energy, and color, it was possible to establish,
      beyond doubt, the right conditions to use these terms to classify specific laser
      radiations. This may help in the correct interpretation of some low-level laser
      therapy (LLLT) experimental results. MATERIALS AND METHODS: In order to achieve
      our objective--maintaining the reader's interest--we use the simplest physical
      concepts and equations necessary for nonphysicists to understand this subject.
      RESULTS: The most important result pointed out through this study is the fact
      that the numerical value for wavelength, normally assigned to commercial lasers,
      should not be used to describe the light propagation inside the tissue.
      CONCLUSION: The knowledge of the relation among the magnitudes discussed in the
      present study and their effects, although it does not add much to the use of a
      laser merely as a cutting instrument, becomes of fundamental significance when
      used to determine the effects that depend on light propagation within biological
      tissue and that do not result only from absorption of light energy. This will
      certainly help in the understanding of phenomena whose causes are attributed to
      the electric and magnetic polarization of laser radiation, as seems to be the
      case observed in laser biostimulation.

PMID- 12513917
TI  - Mucosal reconstruction using an artificial dermis after KTP laser surgery.
AB  - OBJECTIVE: The aim of the present study is to assess the clinical effectiveness
      of the artificial dermis. BACKGROUND DATA: We have previously observed prolonged
      postoperative pain and bleeding in patients receiving potassium titanyl phosphate
      (KTP) laser surgery for oral mucosal diseases. MATERIALS AND METHODS: The
      artificial dermis was placed on the wound and fixed to the surrounding oral
      mucosa by silk suturing. The silicon sheet of the artificial dermis and the
      sutures were removed on the seventh postoperative day. Postoperative bleeding
      from the oral mucosa, duration of postoperative pain, and the period required for
      healing were all assessed clinically. The results were compared to those in a
      group of similar cases which were treated without the artificial dermis. In this
      retrospective review, we considered 20 cases of tongue lesion treated by KTP
      laser (10 leukoplakias, nine squamous cell carcinomas, and one metastatic renal
      cell carcinoma to the tongue), nine of which were followed by application of an
      artificial dermis to prevent postoperative pain and bleeding, and 11 of which
      were not. RESULTS: No postoperative bleeding was observed in the group of cases
      treated with an artificial dermis, although it was observed in 45.5% in the group
      of cases treated without an artificial dermis. There was a statistical difference
      between these two groups (p < 0.03). CONCLUSION: It was concluded that use of
      artificial dermis prevented postoperative bleeding.

PMID- 12513918
TI  - NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone
      marrow transplant patients.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of prophylactic
      near-infrared light therapy from light-emitting diodes (LEDs) in pediatric bone
      marrow transplant (BMT) recipients. BACKGROUND DATA: Oral mucositis (OM) is a
      frequent side effect of chemotherapy that leads to increased morbidity. Near
      infrared light has been shown to produce biostimulatory effects in tissues, and
      previous results using near-infrared lasers have shown improvement in OM indices.
      However, LEDs may hold greater potential for clinical applications. MATERIALS AND
      METHODS: We recruited 32 consecutive pediatric patients undergoing myeloablative
      therapy in preparation for BMT. Patients were examined by two of three pediatric
      dentists trained in assessing the Schubert oral mucositis index (OMI) for left
      and right buccal and lateral tongue mucosal surfaces, while the patients were
      asked to rate their current left and right mouth pain, left and right xerostomia,
      and throat pain. LED therapy consisted of daily treatment at a fluence of 4
      J/cm(2) using a 670-nm LED array held to the left extraoral epithelium starting
      on the day of transplant, with a concurrent sham treatment on the right. Patients
      were assessed before BMT and every 2-3 days through posttransplant day 14.
      Outcomes included the percentage of patients with ulcerative oral mucositis (UOM)
      compared to historical epidemiological controls, the comparison of left and right
      buccal pain to throat pain, and the comparison between sides of the buccal and
      lateral tongue OMI and buccal pain. RESULTS: The incidence of UOM was 53%,
      compared to an expected rate of 70-90%. There was also a 48% and 39% reduction of
      treated left and right buccal pain, respectively, compared to untreated throat
      pain at about posttransplant day 7 (p < 0.05). There were no significant
      differences between sides in OMI or pain. CONCLUSION: Although more studies are
      needed, LED therapy appears useful in the prevention of OM in pediatric BMT
      patients.

PMID- 12513919
TI  - Effects of 630-, 660-, 810-, and 905-nm laser irradiation delivering radiant
      exposure of 1-50 J/cm2 on three species of bacteria in vitro.
AB  - OBJECTIVE: To examine the effects of low-intensity laser therapy (LILT) on
      bacterial growth in vitro. BACKGROUND DATA: LILT is undergoing investigation as a
      treatment for accelerating healing of open wounds. The potential of coincident
      effects on wound bacteria has received little attention. Increased bacterial
      proliferation could further delay recovery; conversely inhibition could be
      beneficial. MATERIALS AND METHODS: Pseudomonas aeruginosa, Escherichia coli, and
      Staphylococcus aureus were plated on agar and then irradiated with wavelengths of
      630, 660, 810, and 905 nm (0.015 W/cm(2)) and radiant exposures of 1-50 J/cm(2).
      In addition, E. coli was irradiated with 810 nm at an irradiance of 0.03 W/cm(2)
      (1-50 J/cm(2)). Cells were counted after 20 h of incubation post LILT. Repeated
      measures ANOVA and Tukey adjusted post hoc tests were used for analysis. RESULTS:
      There were interactions between wavelength and species (p = 0.0001) and between
      wavelength and radiant exposure (p = 0.007) in the overall effects on bacterial
      growth; therefore, individual wavelengths were analyzed. Over all types of
      bacteria, there were overall growth effects using 810- and 630-nm lasers, with
      species differences at 630 nm. Effects occurred at low radiant exposures (1-20
      J/cm(2)). Overall effects were marginal using 660 nm and negative at 905 nm.
      Inhibition of P. aeruginosa followed irradiation using 810 nm at 5 J/cm(2) (-23%;
      p = 0.02). Irradiation using 630 nm at 1 J/cm(2) inhibited P. aeruginosa and E.
      coli (-27%). Irradiation using 810 nm (0.015 W/cm(2)) increased E. coli growth,
      but with increased irradiance (0.03 W/cm(2)) the growth was significant (p =
      0.04), reaching 30% at 20 J/cm(2) (p = 0.01). S. aureus growth increased 27%
      following 905-nm irradiation at 50 J/cm(2). CONCLUSION: LILT applied to wounds,
      delivering commonly used wavelengths and radiant exposures in the range of 1-20
      J/cm(2), could produce changes in bacterial growth of considerable importance for
      wound healing. A wavelength of 630 nm appeared to be most commonly associated
      with bacterial inhibition. The findings of this study might be useful as a basis
      for selecting LILT for infected wounds.

PMID- 12513920
TI  - Sudden and unpredictable below-surface ablation pattern changes by CO2 laser
      beams: a qualitative description of five macroscopic cases observed in PMMA with
      high probability to occur during surgery in low-water-content tissues.
AB  - OBJECTIVE: This paper describes five cases of macroscopic irregular CO(2) laser
      beam ablation patterns that can generate below-surface complications during
      surgery. These five cases are related to curved reflected beams, curved craters
      generation with abnormal superficial thermal damage, and craters that show
      irregular wall contours. Although these alterations have been observed during
      irradiation in PMMA samples (polymethilmethacrylate), it is possible that similar
      unpredictable changes also happen in low-water-content, hard and uniform
      biological tissues such as compact bone, enamel, and dentin. This fact can
      predict severe impacts on the quality of the final surgical outcome, especially
      there where precision surgery techniques are required. A qualitative description
      about the possible causes of these effects and how to avoid them during surgery
      have been suggested too. BACKGROUND DATA: In the past decades, daily surgery and
      research studies have provided useful information about the interaction between
      medical CO(2) laser beams and animal, human, and other biological tissues.
      Several mathematical models describe with acceptable accuracy all the ablative
      properties of the 10.6 microm laser beam. Very few studies describe the presence
      and address the consequences of the ablative aberrations, which can frequently
      and randomly happen during laser surgery. The probability that these changes
      happen in below-surface, therefore invisible, parts of the biologic media under
      treatment makes the whole matter crucial, even in cases of traditional surgery.
      Where gross mass removals are considered, the presence of unpredictable and
      sudden deviations from the expected traditional cone-shaped patterns raise
      several questions about safety. The continuous need for properly engineered
      medical laser-beam devices, online laser-beam monitoring, and real-time control
      becomes mandatory in modern surgery. MATERIALS AND METHODS: The equipment used in
      this study was provided by the National Cancer Institute of Milan, Milan, Italy,
      and by the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. A
      large TEM-mode laser-beam device (Valfivre, Italy) and TEM00 laser-beam device
      (Synrad, USA), both coupled to 2.5- and 5-inch focusing lenses, have been used to
      irradiate, at 10 Watts nominal output, on the focal spot, several PMMA blocks (3
      x 2 x 4 x 2 x 2 cm) up to 10 sec CW. For one set of experiments, a metallic, well
      polished mirror was placed against one surface of each sample to simulate
      possible internal beam reflections caused by generic metallic surgical
      instruments, such as conventional scalpels or clamps. RESULTS: The experimental
      evidence of five major and unpredicted changes in the shape of craters produced
      by CO(2 )laser beams in PMMA are shown in photos and discussed in a qualitative
      way. Several physical and thermodynamic phenomena are proposed to identify and
      therefore minimize or avoid the causes of these events. CONCLUSION: The results
      discussed in this paper show how important it is to constantly and carefully
      observe both the irradiated tissue's or media's structure and the beam's
      broadening under surface during the ablation process. Fume attenuation of the
      incoming laser beam, fume escape paths, internal beam interference phenomena,
      media's microstructural changes and, perhaps more importantly, their combination
      can offer good explanations of all the described phenomena. In summary, the
      presence of fumes in at least two out of the five reported cases plays a key role
      in aberrant crater generation processes. Therefore, the author recommends paying
      extra attention to them in order to provide a higher quality outcome in Surgery
      where CO(2) laser beams are deployed.

PMID- 12513922
TI  - Laser literature watch.

PMID- 12513921
TI  - Contraindications in noninvasive laser therapy: truth and fiction.
AB  - OBJECTIVE: Noninvasive laser therapy is a treatment method employed in many
      disciplines. This review article points out instances when it appears to be
      effective to administer such therapy. MATERIALS AND METHODS: Noninvasive laser
      therapy has a number of suitable applications that cause minimal damage to the
      patient. Many patients are not sent to institutions equipped with relevant
      instruments, since physicians are burdened by a number of contraindications, many
      of which are incorrect. The purpose of this article was to divide these
      contraindications into the following three groups: correct indications,
      indications doubtful under certain conditions, and incorrect indications.
      DISCUSSION: We consider the following contraindications as correct: history of a
      histologically demonstrated malignant carcinoma; irradiation of the neck region
      in hyperthyreosis; epilepsy; exposure of the retina; and exposure of the abdomen
      during pregnancy. The contraindications that are doubtful under certain
      conditions are as follows: fever and infectious diseases; certain blood diseases;
      heavy blood losses; neuropathies; and irradiation in the region of gonads. The
      other contraindications reported in the literature are considered to be
      incorrect.

PMID- 12513923
TI  - A note in the high prevalence of anti-HCV seropositivity among hilltribers in Mae
      Jam District, Northern Thailand.

PMID- 12513924
TI  - Cytotoxic T lymphocytes and neutralizing antibody in the control of equine
      infectious anemia virus.

PMID- 12513925
TI  - Immunological responses of swine to porcine reproductive and respiratory syndrome
      virus infection.
AB  - The immunology of porcine reproductive and respiratory syndrome virus (PRRS)
      begins with an initial encounter of PRRSV with the pig. Regardless of the route
      of entry of PRRSV--via inhalation, intramuscular vaccination, insemination, or
      other routes--productive infection occurs predominately in alveolar macrophages
      of the lung. Thus, innate responses of the lung and the alveolar macrophage
      comprise the initial defense against PRRSV. The virus appears not to elicit
      innate interferon and cytokine responses characteristic of other strongly
      immunogenic viral pathogens, and its effects are consistent with induction of a
      weak adaptive immune response. Humoral and cell-mediated immunity is induced in
      due course, and results in clearance of virus from the circulation but not from
      lymphoid tissues, where the infection becomes persistent. Subsequent reexposure
      to PRRSV elicits an anamnestic response that is partially to completely
      protective. Within this unconventional picture of anti-PRRSV immunity lie a
      variety of unresolved issues, including the nature of protective immunity within
      individual pigs and among pigs in commercial populations, the efficacy of
      protective immunity against genetically different PRRSV isolates, the effects of
      developmental age, sex, genetics, and other host factors on the immune response
      to PRRSV, and the possible suppression of host immunity to other pathogens.

PMID- 12513926
TI  - Cytokine mRNA profiles in bronchoalveolar cells of piglets experimentally
      infected in utero with porcine reproductive and respiratory syndrome virus:
      association of sustained expression of IFN-gamma and IL-10 after viral clearance.
AB  - An experimental model was used to investigate mRNA cytokine profiles in
      bronchoalvolar cells (BALC) from piglets, infected in utero with porcine
      reproductive and respiratory syndrome virus (PRRSV). The BALC's were analyzed for
      the cytokines TNF-alpha, IFN-gamma, IL-8, IL-10, and IL-12(p40) by real-time
      TaqMan polymerase chain reaction in 2-, 4-, and 6-week-old piglets, respectively.
      High levels of IFN-gamma mRNA was detected in all piglets, while IL-10 was
      upregulated in 2-week-old piglets, was at normal levels in 4-week-old piglets,
      and elevated again in 6-week-old piglets. IL-12 was weakly elevated in all three
      age groups. Virus was reduced by 50% in 4-week-old piglets and cleared by 6 weeks
      of age. The sustained expression of IFNgamma and reduction of IL-10 production
      indicate an important role for these cytokines in immunity to PRRSV.

PMID- 12513927
TI  - Adjuvant danger signals increase the immune response to porcine reproductive and
      respiratory syndrome virus.
AB  - The immune response of swine to vaccination with a live, attenuated PRRSV was
      assessed in the presence and absence of cytokine adjuvants or cholera toxin (CT)
      to address the hypothesis that adjuvant danger signals, that is, inflammatory
      cytokines and bacterial extoxin, stimulate a more robust immune response. Animals
      received four injections of recombinant porcine IL-1 and IL-6, IL-12 alone, or CT
      alone within 1 week of intramuscular administration of a vaccine strain of PRRSV,
      Ingelvac MLV. Serological and cell-mediated responses were monitored for 42 days
      after vaccination and for a further 10 days after challenge with the virulent
      VR2332 strain of PRRSV. First, the principal observation was an enhancing effect
      of IL-12 on the interferon gamma response to PRRSV, with a more rapid and
      heightened PRRSV-specific interferon gamma ELISPOT response in peripheral blood
      mononuclear cells. The more rapid and robust development of a cell-mediated
      immune response, as determined by this assay, suggests that IL-12 may influence
      the induction of antigen-specific T cell responses. Second, animals that received
      CT adjuvant displayed a more robust antibody response to GP5, the major envelope
      glycoprotein. Anti-GP5 titers peaked at 21 days after vaccination at more than
      twice the level of any other treatment, for which the peak response was at 28
      days. Third, there was no evidence of PRRSV immunosuppression of immunity to
      unrelated antigens, including circovirus. CT is a potent mucosal adjuvant,
      particularly for antibody responses. It acts in part through the production of IL
      1 in macrophages, but its effect was not replaced by combination treatment with
      IL-1 and IL-6. In sum, the results suggest that cytokine adjuvants, particularly
      IL-12, and CT have the potential to enhance immune responses to live viral
      vaccines.

PMID- 12513928
TI  - Immunologic features of porcine circovirus type 2 infection.
AB  - Clinical expression of porcine circovirus 2 (PCV-2) infection in swine may result
      in two distinct high mortality disease syndromes. In North America, postweaning
      multisystemic wasting syndrome (PMWS), while still sporadic in incidence,
      predominates. In Europe and elsewhere, both PMWS and a second syndrome, porcine
      dermatitis and nephropathy syndrome (PDNS), occur in endemic and epidemic forms.
      PMWS but not PDNS has been reproduced in piglets by inoculations with PCV-2 alone
      or in PCV-2-infected swine co-infected with porcine parvovirus (PPV) or porcine
      respiratory and reproductive syndrome (PRRS) virus and also if PCV-2-infected
      piglets are immunostimulated by injections with an immunogen emulsified in an oil
      based macrophage-targeted adjuvant. Subclinical but active infection has been
      achieved by direct inoculation of piglets with cloned PCV-2 DNA and/or progeny
      virus derived from cloned DNA. Morphologic changes in lymphoid tissues and
      preliminary functional data suggest that immunosuppression may occur in PMWS
      affected swine. This phenomenon appears to be mediated by generalized lymphoid
      depletion and replacement by infiltrating and proliferating histiocytes and
      macrophages. Accumulation of virus in both mononuclear phagocytes and follicular
      dendritic cells is characteristic of PCV-2 infection. Exogenous immunosuppression
      of PCV-2-infected gnotobiotic piglets with cyclosporine (Cys), but not
      corticosteroid (St), potentiates PCV-2 replication and promotes productive virus
      infection of hepatocytes in Cys-treated piglets, a tropism not previously
      apparent in experimentally induced PMWS in gnotobiotic swine. In the Cys-treated
      piglets, inflammatory lesions characteristic of PMWS are absent, even though
      tissues contain high titers of infectious virus, a finding which suggests that
      the granulomatous inflammatory lesions characteristic of PMWS are immune
      mediated.

PMID- 12513929
TI  - Correlations between lung proinflammatory cytokine levels, virus replication, and
      disease after swine influenza virus challenge of vaccination-immune pigs.
AB  - During experimental infection of pigs with swine influenza virus (SIV), there is
      a strong temporal correlation between peak virus titers in the lungs, levels of
      different proinflammatory cytokines in bronchoalveolar lavage (BAL) fluids, and
      disease. Vaccination against SIV can greatly reduce or prevent virus replication
      after challenge and the resulting disease. Here, we took advantage of pigs from
      vaccination-challenge experiments, with different degrees of virological and
      clinical protection, to further correlate SIV replication with cytokines and
      disease. Forty-nine pigs were vaccinated twice with a commercial inactivated SIV
      vaccine or with experimental vaccines, and 35 control pigs were not vaccinated.
      Between 2 and 4 weeks after the last vaccination, all pigs were challenged
      intratracheally with SIV. Twenty-four hours after the challenge, we determined
      body temperatures, respiratory scores, lung virus titers, and neutrophils and
      cytokines in BAL fluids. Interferon-alpha (IFN-alpha), tumor necrosis factor (TNF
      alpha), interleukin-1 (IL-1), and -6 (IL-6) were determined by bioassay, and IL-8
      by a commercial ELISA. The results were analyzed for three comparison groups. The
      unvaccinated control pigs (group 1, n = 35) were positive for all or most
      parameters examined. Vaccinated pigs with challenge virus replication in the
      lungs (group 2, n = 28) had slightly lower virus titers than the challenge
      control pigs, and clear reductions in disease severity and mean titers of all
      five cytokines, but neutrophil numbers were not affected. Vaccinated pigs without
      detectable virus replication (group 3, n = 21) were largely protected against
      clinical signs and neutrophil infiltration. Mean levels of IFN-alpha, TNF-alpha,
      and IL-6, but not IL-1 or IL-8, were lower than in both other groups. Virus
      titers in the lungs of individual pigs showed highly significant correlations
      with IFN-alpha and IL-6, and lower correlations with TNF-alpha and IL-8. Clinical
      signs were most closely associated with IFN-alpha, IL-6, and TNF-alpha. The
      relationship between disease and IL-8 or IL-1 was much weaker. Our data provide
      further evidence for a role of IFN-alpha, TNF-alpha, and IL-6 in the pathogenesis
      of SIV. The similarities with cytokine profiles during human influenza virus
      infection are discussed.

PMID- 12513930
TI  - Effects of virion host shut-off activity of bovine herpesvirus 1 on MHC class I
      expression.
AB  - Previously, we have shown that bovine herpesvirus 1 (BHV-1) down-regulates the
      expression of major histocompatibility complex class I molecules by interfering
      with transport of peptides by the transporter associated with antigen processing
      (TAP). Further studies revealed that BHV-1 down-regulates the expression of mRNA
      for class I molecules and other cellular proteins. To further elucidate the
      mechanisms of down-regulation of class I molecules, a virion host shut-off (vhs)
      deletion mutant was generated. The mutant, like the wildtype (wt) virus,
      interfered with transport of peptides by the TAP, and down-regulated cell surface
      expression of class I molecules. However, unlike the wt virus, the mutant did not
      impair the synthesis of class I molecules. These results indicate that down
      regulation of class I molecules by BHV-1 is mediated by vhs activity of the
      virus, as well as mechanisms specifically directed at the class I pathway.
      Absence of vhs activity should result in decreased pathogenicity and enhanced
      immunogenicity of BHV-1 vhs deletion mutant, making it a better vaccine
      candidate.

PMID- 12513931
TI  - Hantavirus immunology.
AB  - Two clinical syndromes are associated with hantavirus infection in humans:
      hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome
      (HPS). Autopsy findings typically reveal a common feature of increased
      permeability in microvascular beds, suggesting vascular endothelium is a prime
      target for virus infection. Endothelial cells are susceptible to hantavirus
      infection; however, virus does not cause cytopathic effects, to explain increased
      endothelium permeability. Therefore, immune mechanisms were suggested to play a
      crucial role in hantavirus pathogenesis. In this review, we summarize data on
      hantavirus-induced immune disturbances and discuss their implication in capillary
      leakage caused by hantavirus infection.

PMID- 12513932
TI  - Chimeric bacteriophage fr virus-like particles harboring the immunodominant C
      terminal region of hamster polyomavirus VP1 induce a strong VP1-specific antibody
      response in rabbits and mice.
AB  - The late region of the hamster polyomavirus (HaPyV, former HaPV) genome encodes
      three structural proteins VP1, VP2, and VP3, where VP1 represents the major
      capsid protein of 384 amino acids. Screening of sera from HaPyV-infected
      papilloma-bearing and papilloma-free hamsters demonstrated the immunodominant
      features of all three capsid proteins. For both groups of hamsters in the C
      terminal region of VP1 immunodominant B-cell epitopes were identified in the
      regions between amino acids 305 and 351 and amino acids 351 and 384. The high
      flexibility of the C-terminal region of VP1 was confirmed by the formation of
      chimeric virus-like particles based on the coat protein of the RNA bacteriophage
      fr which was previously found to tolerate only very short-sized foreign
      insertions. Phage fr coat protein-derived virus-like particles tolerated the N
      terminal fusion of amino acids 333-384, 351-384, 351-374, and 364-384,
      respectively, of VP1. The induction of VP1-specific antibodies in rabbits and
      mice by immunization with chimeric virus-like particles harboring amino acids 333
      384, 351-384, and 364-384, respectively, of VP1 suggested the immunodominant
      nature of the C-terminal region of VP1.

PMID- 12513933
TI  - What are the research priorities of Canadian dentists?
AB  - A joint CDA-Institutes of Musculoskeletal Health and Arthritis study was
      undertaken to evaluate the dental research priorities of Canadian dentists. A
      self-complete questionnaire was sent to all dentists in Canada with the December
      2001 JCDA. This last article in a 3-part series presents the results on funding
      priorities. By April 1, 2002, 2,788 questionnaires, representing a response rate
      of approximately 16%, had been returned. Of 8 broad areas of research,
      respondents identified areas related to treatments as the most important: 77%
      cited the evaluation of the effectiveness of techniques and treatments as high
      priority, 76% the development of treatments and 70% the development of materials.
      The areas judged less important were improvements in access to care (42%) and a
      better understanding of patient behaviour (25%). With respect to more specific
      research topics, the highest priority subjects were dental materials other than
      amalgam and periodontal diseases.

PMID- 12513934
TI  - Life-threatening hemorrhage after extraction of third molars:case report and
      management protocol.
AB  - Few dental procedures have fatal complications, but severe postoperative
      hemorrhage can result in preventable death. This report describes a case of
      postextraction hemorrhage that led to airway compromise necessitating emergency
      airway management. This complication is rare, and a review of the literature
      revealed little in the way of case reports and treatment protocols. This article
      reviews the causes of and risk factors related to severe postoperative bleeding
      and presents an algorithm for management both in the dental office and in the
      hospital.

PMID- 12513935
TI  - Management of traumatic dislocation of the mandibular condyle into the middle
      cranial fossa.
AB  - Dislocation of the mandibular condyle into the middle cranial fossa is a rare
      complication of facial trauma that can have neurological and life-threatening
      implications. This article discusses the anatomic features that predispose
      patients to this type of injury, as well as the clinical features and mechanism
      of injury for this rare type of condylar deformity, to help practitioners
      recognize this easily overlooked injury and avoid disastrous complications. The
      article summarizes previously published case reports of this rare complication of
      condylar trauma and presents a case for which initial diagnosis and a management
      protocol are described.

PMID- 12513936
TI  - Antiplatelet drugs : is there a surgical risk?
AB  - Acetylsalicylic acid has long been the only nonsteroidal anti-inflammatory drug
      recommended for the treatment and prevention of thromboembolic diseases. More
      recently, new compounds have been used in patients with vascular diseases.
      However, these drugs are often associated with longer bleeding times and greater
      operative risk. In most surgical specialties, the question always arises as to
      whether antiplatelet therapy should be stopped before elective surgery. If so,
      for how long? If not, what are the risks? This article reviews the various
      antiplatelet drugs in use today, focusing on their mode of action, their effects
      on platelet function and the associated operative risks. It also proposes an
      algorithm for decision making in this setting, based on the literature and an
      understanding of the mechanisms of action of this class of drugs.

PMID- 12513937
TI  - Frequency of pharyngoplasty after primary repair of cleft palate.
AB  - BACKGROUND: The frequency of pharyngoplasty after initial repair of cleft palate
      is a direct measure of the success or failure of the primary palatal repair with
      respect to velopharyngeal function. The optimal timing and surgical technique for
      the repair of cleft palate remain subjects of debate. PURPOSE: To assess the
      outcome of various techniques for primary palatal repair, specifically the
      frequency of secondary pharyngoplasty, and to determine the significance, if any,
      of certain variables to this outcome. METHODS: A pool of 114 patients with cleft
      lip and palate was compiled from a retrospective analysis of medical records for
      more than 300 consecutive patients treated over a 15-year period (1980-1995). The
      review included only patients who had been treated by the same surgeon or by his
      resident. A 1-stage palatal repair was performed on all patients, in which the
      hard and the soft palate were closed simultaneously. The following data were
      collected: patient's sex, patient's date of birth, type of cleft, technique used
      for initial repair, age at initial repair and date of secondary pharyngoplasty
      surgery, if performed. RESULTS: The overall frequency of subsequent
      pharyngoplasty was 25% (28 patients). The rate of secondary surgery was
      significantly higher for boys (21/63 or 33%) than for girls (7/51 or 14%). There
      were also significant differences in the rate of secondary pharyngoplasty
      according to type of cleft: 50% (6/12) for patients with bilateral cleft lip and
      palate, 44% (7/16) for those with hard and soft cleft palate, 21% (8/38) for
      those with unilateral cleft lip and palate, 20% (3/15) for those with submucous
      cleft palate and 12% (4/33) for those with soft cleft palate. Surgical technique
      for the primary repair (V-Y pushback or von Langenbeck procedure) was not a
      significant factor in determining the rate of subsequent pharyngoplasty, nor was
      age at primary repair, although those who underwent primary repair at age 12-14
      months were least likely to require pharyngoplasty. CONCLUSION: In this study the
      frequency of velopharyngeal insufficiency after 1-stage palatoplasty was
      consistent with previously reported results. Of interest would be a comparison of
      1-stage and 2-stage approaches to primary palate repair in young patients.

PMID- 12513938
TI  - Temporomandibular joint arthroscopic findings in patients with cervical flexion
      extension injury (whiplash): a preliminary study of 30 patients.
AB  - PURPOSE: To investigate arthroscopic findings for the temporomandibular joint
      (TMJ) in 30 patients with refractory TMJ symptoms who had suffered cervical
      flexion-extension injury (whiplash). METHODS: The clinical data and operative
      reports of all patients with a diagnosis of TMJ whiplash injury who underwent TMJ
      arthroscopic procedures from 1997 to 2002 were reviewed. All patients underwent
      preoperative clinical, panoramic, arthrographic, magnetic resonance imaging
      evaluation or computed tomography (or some combination). The same surgical team
      performed all diagnostic and therapeutic arthroscopic procedures in patients for
      whom conservative therapy had failed. Before the arthroscopic surgery, all of the
      patients had received at least 3 to 6 months of nonsurgical therapy consisting of
      anti-inflammatory medications, muscle relaxants, splint therapy, physiotherapy
      (specifically transcutaneous electrical nerve stimulation, moist heat, cold
      laser, and ultrasonography) and a soft diet. RESULTS: A spectrum of arthroscopic
      findings, ranging from chondromalacia (softening of the articular fibrocartilage)
      to moderate or severe synovitis and adhesions, was observed, as well as
      combinations of these abnormalities. CONCLUSION: The primary intracapsular
      pathologic changes observed during TMJ arthroscopic examination of 30 patients
      who suffered cervical whiplash injury appear to be nonspecific, varying along a
      wide spectrum of findings.

PMID- 12513940
TI  - Chaos and schizophrenia: does the method fit the madness?
AB  - Over the past 30 years, investigators have used nonlinear and so-called chaos
      theory-based techniques to examine a wide range of phenomena ranging from
      electroencephalogram and cardiac rate and rhythm analyses to stock market and
      weather predictions. Psychiatric neuroscientists are now beginning to apply
      nonlinear methods to mental disorders such as schizophrenia. These applications
      are relevant from the level of complex genetic architecture and calcium channel
      dynamics to the symptomatic, behavioral, and functional outcome of schizophrenia.
      The key point of this surge of interest is distinguishing complex, nonlinear but
      lawfully mediated systems from truly random systems. The application of these
      methods to studies in schizophrenia has yielded findings that are consistent with
      the general hypothesis that an altered sequential or temporal architecture is a
      key feature of this disorder. Specifically, we propose that the temporal
      architecture of schizophrenia is characterized by bursts of complex, nonlinear
      phenomena alternating with truly random events. Analyzing these patterns of
      molecular (e.g., calcium channel activity) to molar (e.g., symptom level)
      phenomena via nonlinear systems methods can provide new approaches to
      understanding complex temporal and sequential shifts in neural substrate
      activity, pathophysiology, and the course and treatment and outcome of
      schizophrenia.

PMID- 12513941
TI  - Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and
      secondary compensations.
AB  - BACKGROUND: Working memory (WM) deficits are well known in schizophrenia and have
      been associated with abnormal activation patterns of the prefrontal cortex (PFC)
      during cognitive performance. The magnitude and particularly the direction of the
      PFC activation -- i.e., increased (hyperfrontality) or decreased (hypofrontality)
      -- in schizophrenia, as well as its pathophysiological implications, remain
      controversial. Working memory is supported by a distributed neural network, whose
      main components are the PFC and the posterior parietal (PPC) cortices. Monkey
      studies indicate that, during WM performance, PFC functional lesions may be
      compensated by the PPC if task demands center mainly on anticipating responses,
      but not if they center on remembering cues. We hypothesized that a primarily
      dysfunctional PFC in schizophrenia might show hypofrontality or hyperfrontality
      as a result, respectively, of efficient or inefficient PPC compensation, as
      dictated by task demands. To test our proposition, we biased the demands of WM
      tasks toward anticipating responses or remembering cues and measured its impact
      on the PFC-PPC functional balance in a group of schizophrenic patients and one of
      normal control subjects. METHODS: We used functional magnetic resonance imaging
      to measure correlates of neuronal activity in the PFC and PPC of schizophrenic
      patients and control subjects performing WM tasks that either demanded
      information retention or allowed for response anticipation. RESULTS: When
      compared to control subjects, schizophrenic patients exhibited decreased PFC
      activation and increased PPC activation during anticipatory WM performance, and
      increased PFC activation during mnemonic WM performance. CONCLUSIONS: In
      schizophrenia, a PFC dysfunction results in hypo- or hyperfrontality as a
      function of whether other alternate areas of a PFC-PPC network for WM are
      available and efficacious in supporting specific task demands.

PMID- 12513942
TI  - Prefrontal cortex dysfunction mediates deficits in working memory and prepotent
      responding in schizophrenia.
AB  - BACKGROUND: Schizophrenic patients show deficits in working memory (WM) and
      inhibition of prepotent responses. We examined brain activity while subjects
      performed tasks that placed demands on WM and overriding prepotent response
      tendencies, testing predictions that both processes engage overlapping prefrontal
      cortical (PFC) regions and that schizophrenic patients show reduced PFC activity
      and performance deficits reflecting both processes. METHODS: Functional magnetic
      resonance imaging data were acquired while 16 schizophrenic and 15 healthy
      subjects performed the N-Back task that varied WM load and a version of the AX
      CPT that required overriding a prepotent response tendency. RESULTS: Both tasks
      engaged overlapping cortical networks (e.g., bilateral dorsolateral PFC, Broca's
      area, parietal cortex). Increased WM load monotonically increased activity;
      preparation to override a prepotent response produced greater and more enduring
      activity. Group differences on each task emerged in a right dorsolateral PFC
      region: schizophrenic subjects showed lesser magnitude increases under conditions
      of high WM and prepotent response override demands, with concomitant performance
      impairments. CONCLUSIONS: Schizophrenic patients exhibit PFC-mediated deficits in
      WM and preparation to override prepotent responses. Findings are consistent with
      the operation of a single underlying PFC-mediated cognitive control mechanism and
      with physiologic dysfunction of the dorsolateral PFC in schizophrenic patients
      reflecting impairments in this mechanism.

PMID- 12513943
TI  - MRNA expression patterns and distribution of white matter neurons in dorsolateral
      prefrontal cortex of depressed patients differ from those in schizophrenia
      patients.
AB  - BACKGROUND: Schizophrenia, bipolar illness, and major depressive disorder have
      distinct presentations, but share some common symptoms. Hence, some common
      cellular and molecular abnormalities may be identifiable in these disorders.
      METHODS: We examined cell-specific markers in the dorsolateral prefrontal cortex
      of brains from 18 patients with bipolar or major depressive disorder, and 18
      matched controls, using in situ hybridization histochemistry and staining for
      nicotinamide-dinucleotide phosphate-diaphorase (NADPH). The distribution of NADPH
      positive interstitial cells of the white matter and the expression of the mRNA
      for the 67 KD form of glutamic acid decarboxylase (GAD(67)) had previously been
      shown to be altered in prefrontal cortex of schizophrenics. Other markers
      identifying glutamatergic neuronal populations were alpha-type II
      calcium/calmodulin dependent protein kinase (CAMKII-alpha), brain derived
      neurotrophic factor, (BDNF) and the putative transcription factor, T-brain-1
      (TBR1). RESULTS: Expression of GAD67 and the distribution of NADPH-positive cells
      in the white matter were not significantly altered in the dorsolateral prefrontal
      cortex of depressed subjects. Expression of CAMKII-alpha and TBR1 mRNAs was
      significantly increased in bipolar patients but not in major depressed patients,
      and there was a trend toward reduced BDNF expression in both groups. Abnormal
      patterns of gene expression and neuronal distribution in schizophrenics are
      markedly different from those in depressed patients. CONCLUSIONS: The findings
      that TBR1 and CAMKII-alpha expression is increased only in bipolar patients
      suggests abnormalities of specific genes related to a major cortical cell type
      and its connectivity.

PMID- 12513944
TI  - Impaired hippocampal recruitment during normal modulation of memory performance
      in schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed
      to impaired prefrontal and hippocampal function. Healthy adults can increase
      recall accuracy following encoding interventions, such as item repetition and the
      formation of semantic associations. We examined the effects of these
      interventions on both memory performance and retrieval-related hippocampal
      activity in healthy adults and patients with schizophrenia. METHODS: Twelve
      patients with schizophrenia and twelve healthy control subjects participated.
      During study, subjects counted either the number of meanings or T-junctions in
      words seen only once or repeated four times. At test, O15-positron emission
      tomography scans were acquired while subjects completed word-stems with
      previously studied items. RESULTS: Control subjects recalled more words overall,
      but both groups demonstrated similar performance benefits following deeper
      encoding. Both item repetition and the use of a semantic encoding task were
      associated with memory retrieval-related hippocampal recruitment in control but
      not schizophrenic participants. Patients with schizophrenia demonstrated greater
      activation of prefrontal cortical areas during word retrieval. CONCLUSIONS:
      Despite a lack of hippocampal recruitment, patients with schizophrenia showed
      intact modulation of memory performance following both encoding interventions.
      Impaired hippocampal recruitment, in concert with greater prefrontal activation,
      may reflect a specific deficit in conscious recollection in schizophrenia.

PMID- 12513945
TI  - Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated
      and medicated schizophrenia patients.
AB  - BACKGROUND: Reduced levels of membrane essential polyunsaturated fatty acids
      (EPUFAs) and increased levels of lipid peroxidation products (thiobarbituric acid
      reactive substances; TBARS) have been observed in chronic medicated
      schizophrenics. The relationship of EPUFA and TBARS to psychopathology is
      unclear, since their levels may be altered differentially by duration of illness
      and antipsychotic treatment. To minimize these confounds, their levels were
      compared among never-medicated patients in early illness, medicated patients and
      control subjects with similar lifestyle and common ethnic background. METHODS:
      RBC membrane EPUFAs, plasma TBARS, and various dimensions of psychopathology were
      measured using established procedures in never-medicated (n = 20) and medicated
      (n= 32) schizophrenia patients and in control subjects (n= 45). RESULTS: Reduced
      levels of EPUFAs, particularly arachidonic acid (AA) and docosahexaenoic acid
      (DHA), were found in never-medicated compared with control subjects; however, the
      reductions in levels of both AA and DHA were much smaller in medicated versus
      never-medicated patients; AA levels were similar to levels in control subjects.
      Only DHA levels were significantly reduced in medicated patients. Lower membrane
      AA levels were associated with increased levels of plasma TBARS in never
      medicated patients. Lower levels of membrane EPUFAs and higher levels of plasma
      TBARS were associated with the severe symptoms in never-medicated versus
      medicated patients. CONCLUSIONS: Data indicate that reduced EPUFAs and increased
      TBARS exist in never-medicated patients, and these measures correlate with the
      severity of psychopathology indicating that the membrane EPUFA status may reflect
      the outcome of schizophrenia.

PMID- 12513946
TI  - Decision making by methamphetamine-dependent subjects is associated with error
      rate-independent decrease in prefrontal and parietal activation.
AB  - BACKGROUND: One important aspect in decision making is how success or failure
      influences the selection of a response. In a previous investigation,
      methamphetamine-dependent subjects (MD) selected win-stay/lose-shift consistent
      responses than normal comparison subjects (NC), which may imply that MD are more
      influenced by success. This study examined whether the degree of success and the
      degree of predictability differentially affected MD's decision making. METHODS:
      Using functional magnetic resonance imaging, 14 MD were compared with 14 NC while
      performing the two-choice prediction task at three success rates and the two
      choice response task. RESULTS: The increase in win-stay/lose-shift consistent
      responses by MD relative to NC was independent of success rate. Irrespective of
      success, MD showed less task-related activation in orbitofrontal cortex
      (Brodmann's area [BA] 10), dorsolateral prefrontal cortex (BA 9), anterior
      cingulate (BA 32), and parietal cortex (BA 7). Whereas NC showed success-related
      patterns of neural activation in the orbitofrontal, dorsolateral prefrontal, and
      parietal cortex, MD showed activation that was highest when the outcome was most
      unpredictable. CONCLUSIONS: Our results are consistent with the hypothesis of a
      more rigid stimulus-response relationship during MD's decision making, which may
      be due to a shift from processing "success" toward processing the degree of
      stimulus "predictability."

PMID- 12513947
TI  - Hypothalamic-pituitary-adrenal system adaptation to detoxification in alcohol
      dependent patients is affected by family history of alcoholism.
AB  - BACKGROUND: Alcohol withdrawal profoundly affects the hypothalamic-pituitary
      adrenocortical (HPA) system. We investigated whether a family history of
      alcoholism modulates HPA response to pharmacologic intervention during
      detoxification in alcohol-dependent patients. METHODS: Sixteen family history
      negative (FH-N) and 19 family history positive (FH-P) alcohol-dependent patients
      were admitted for withdrawal. All 35 patients were investigated 1 week after
      remission of withdrawal symptoms; 17 patients were also tested during acute
      withdrawal. Dexamethasone 1.5 mg was given orally at 11 PM, followed by 100
      microg corticotropin-releasing hormone (hCRH) administered intravenously at 3 PM
      the following day. Plasma adrenocorticotropic hormone (ACTH) and cortisol
      concentrations were determined at 0, 30, 45, 60, and 75 min after CRH. RESULTS:
      During withdrawal, cortisol but not ACTH secretion was increased in patients
      compared with 19 control subjects matched for age and gender. After withdrawal,
      cortisol was normal in FH-P but still increased in FH-N patients versus control
      subjects, and ACTH was marginally decreased in FH-P patients only. Both hormones
      were increased in FH-N versus FH-P patients. CONCLUSIONS: Recovery from alcohol
      withdrawal-induced impairment of HPA system regulation occurs earlier in FH-P
      than FH-N patients, indicating that the efficacy of central neuroadaptation to
      this ethanol-related stimulus may be related to genetic factors.

PMID- 12513948
TI  - The A9 allele of the dopamine transporter gene is associated with delirium
      tremens and alcohol-withdrawal seizure.
AB  - BACKGROUND: The dopamine transporter (DAT) plays a key role in homeostatic
      regulation of dopaminergic neurotransmission and could thus be involved in the
      variability of two severe alcohol-withdrawal symptoms, alcohol-withdrawal seizure
      (AWS) and delirium tremens (DT). Interestingly, an association was found between
      the DAT gene (9-copy repeat) and the risk for these symptoms in two previous case
      control studies. METHODS: We reanalyzed the role of the DAT gene in the lifetime
      risk for AWS and DT in 120 alcohol-dependent patients, taking into account
      potentially confounding factors. RESULTS: Alcohol-dependent patients with the
      A(9) allele had experienced AWS or DT at least once (odds ratio [OR] = 2.52, p
      =.03). This association persisted when excluding patients with antisocial
      personality comorbidity (OR = 3.48, p =.02) or limiting the analysis to older
      patients (OR = 8.3, p =.0008). CONCLUSIONS: This study provides convergent data
      in favor of a significant role of the DAT gene in the risk for some severe
      withdrawal symptoms. If further replicated in larger samples, the DAT genetic
      polymorphism could be one of the factors to be analyzed to further assess the
      risk of some severe alcohol-withdrawal symptoms.

PMID- 12513949
TI  - Revisiting the association between attention-deficit/hyperactivity disorder and
      anxiety disorders: a familial risk analysis.
AB  - BACKGROUND: This study tested competing hypotheses about patterns of familial
      association between attention-deficit/hyperactivity disorder (ADHD) and anxiety
      disorders using familial risk analysis methodology. METHODS: The risk for ADHD
      and anxiety disorders in first-degree relatives was examined after stratifying
      ADHD probands by the presence or absence of comorbid anxiety disorders. The
      presence of anxiety disorders in probands and relatives was defined as meeting
      DSM-III-R diagnostic criteria for > or = 2 anxiety syndromes in the same subject.
      RESULTS: Familial risk analyses revealed that 1) the risk for anxiety disorders
      was significantly higher in ADHD probands and their relatives than in control
      probands and their relatives; 2) the risk for anxiety disorders among the
      relatives of ADHD probands was limited to those families in which the proband had
      a diagnosis of ADHD; 3) the risk for anxiety disorders was significantly higher
      among the relatives of ADHD probands with anxiety disorders than in relatives of
      ADHD probands without anxiety disorders, but these two groups did not differ in
      the familial risk for ADHD; and 4) ADHD and anxiety disorders did not cosegregate
      within families, and there was no evidence for nonrandom (assortative) mating.
      CONCLUSIONS: These findings are most consistent with the hypothesis that ADHD and
      anxiety disorders segregate independently in families.

PMID- 12513950
TI  - Cerebral blood volume and clinical changes on the third day of placebo
      substitution for SSRI treatment.
AB  - BACKGROUND: Interruptions in SSRI treatment have been associated with adverse
      effects that can resemble depressive illness. We hypothesized that brain regions
      implicated in depression, with extensive serotonergic innervation, would exhibit
      changes in activity associated with emergence of symptoms following drug
      discontinuation. METHODS: Subjects meeting DSM-IV criteria for remitted major
      depression on 20 mg/day of either fluoxetine or paroxetine were recruited into
      this 6-week study. During weeks 2 and 6, subjects underwent a 3-day period in
      which either active drug or placebo was substituted for their medication under
      double-blind conditions. Cerebral blood volume (CBV) maps were obtained via
      dynamic susceptibility magnetic resonance imaging at the end of each double-blind
      period. RESULTS: In the paroxetine group, change in CBV in left medial superior
      frontal region and left caudate nucleus correlated significantly with change in
      Discontinuation Emergent Symptom Scale and Hamilton Depression Rating Scale
      (HDRS; R2 = 0.66, p =.0007; R2 = 0.51, p =.006; and R2 = 0.43, p =.015; R2 =
      0.32, p =.043, respectively). CONCLUSIONS: These data demonstrate that changes in
      regional CBV of left prefrontal cortex and left caudate nucleus correlate with
      the emergence of discontinuation symptoms and increased HDRS after interruption
      of paroxetine treatment.

PMID- 12513951
TI  - Annals of surgical oncology impact factor/rating has dramatically increased.

PMID- 12513952
TI  - Current therapy for childhood thyroid cancer: optimal surgery and the legacy of
      king pyrrhus.

PMID- 12513953
TI  - The future of cancer management: translating the genome, transcriptome, and
      proteome.
AB  - Predicting who will develop cancer and how the cancer will behave and respond to
      therapy after diagnosis are some of the potential benefits of the ongoing genetic
      revolution that can be envisioned within the next decade. Translational
      applications of genomic-based research efforts may actually precede the
      development of effective therapeutic agents that can exploit the vast amounts of
      data derived from these efforts. In the future, understanding the wealth of
      information generated by high-throughput molecular efforts and how it can be
      applied to clinical problems will likely be critical to the surgeon who guides
      the multidisciplinary care of the cancer patient. This review will discuss the
      advances in our understanding of the human genome (DNA), its derived
      transcriptome (RNA), and its translated proteome (proteins) and will focus on the
      translation of this information into routine clinical practice. In particular, we
      will focus on the potential for clinical application of microarray-based gene
      expression profiling to the diagnosis, prognosis, and therapy of malignancies.

PMID- 12513954
TI  - Surgical experience in children with differentiated thyroid carcinoma.
AB  - BACKGROUND: The optimal surgical treatment in children with well-differentiated
      thyroid carcinoma remains an important point of discussion. In this study, we
      evaluated our surgical experience and reviewed the literature accordingly to
      identify the most adequate treatment. METHODS: We retrospectively analyzed 21
      children, all under the age of 18 years at the time of diagnosis, with
      differentiated thyroid carcinoma (17 papillary, 3 follicular, and 1 Hurthle cell
      carcinoma). Total thyroidectomy was performed, followed by radioiodine therapy,
      as a part of the initial treatment in all patients. The results were compared
      with data from the literature. RESULTS: Eleven children (52%) who presented with
      cervical lymph node metastases were treated by a modified radical neck
      dissection. Pulmonary metastases were seen at diagnosis in three patients. Six
      patients developed temporary complications. During follow-up, with a median of 11
      years (range, 2-26 years), two patients (10%) developed recurrences, and no
      patient died during this observation period. A literature search confirmed our
      experience of excellent results without an increase of complications in the more
      aggressively treated patients. CONCLUSIONS: In children with differentiated
      thyroid cancer, treatment should consist of total thyroidectomy, followed by a
      modified radical neck dissection (when indicated) and iodine-131 ablation
      treatment. This aggressive approach seems to be justified because of the high
      incidence of nodal involvement and the low complication and recurrence rate after
      surgery.

PMID- 12513955
TI  - Sentinel lymph node biopsy for head and neck melanomas.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy for head and neck (H&N) melanomas
      may be more technically challenging compared with other locations because of
      complex lymphatic drainage patterns. This analysis was performed to compare the
      results of SLN biopsy for H&N, truncal, and extremity melanomas. METHODS: The
      Sunbelt Melanoma Trial includes patients aged 18 to 70 with melanomas > or = 1.0
      mm thick. Statistical comparison was performed by chi2 or analysis of variance
      test. RESULTS: A total of 2610 patients were evaluated with a median follow-up of
      18 months. The mean number of SLN per nodal basin was 2.8, 2.7, and 2.1 for H&N,
      truncal, and extremity melanomas, respectively. Median Clark level, Breslow
      thickness, and percentage of ulceration were similar between the groups. Peri
      parotid SLN was identified in 25% of cases; there were no facial nerve injuries.
      SLN biopsy for H&N melanoma had higher false-negative rates at 1.5% (vs. 0.5% for
      trunk or extremity) but less histologically positive SLN at 15% (vs. 23.4%, and
      19.5%; P <.001) compared with truncal and extremity melanoma. Blue dye was
      visualized less frequently in SLN of H&N melanoma patients compared with those
      with trunk or extremity melanomas. CONCLUSIONS: Preoperative lymphoscintigraphy
      and meticulous intraoperative search for blue/radioactive nodes may improve
      results in H&N melanomas.

PMID- 12513956
TI  - Prediction of nonsentinel lymph node status in melanoma.
AB  - BACKGROUND: Most melanoma patients with a positive sentinel lymph node dissection
      (SLND) undergo a completion lymph node dissection (CLND) that does not yield
      additional positive nonsentinel lymph nodes (NSLN). This study was designed to
      determine if NSLN status can be predicted using patient, primary tumor, and
      sentinel lymph node (SLN) characteristics. METHODS: The study population includes
      melanoma patients who had a positive SLND and subsequently underwent CLND
      retrieved from our prospective institutional melanoma database. The primary tumor
      and SLN pathologies were prospectively determined. An Size/Ulceration (SU) score
      was derived by assigning 1 point for primary tumor ulceration and 1 point for SLN
      tumor size >2 mm. RESULTS: Ninety-eight patients had a positive SLND and
      underwent CLND. Sixteen of these patients had a positive NSLN. On univariate
      analysis, primary tumor characteristics (thickness, ulceration, no regression),
      SLN metastasis characteristics (size >2 mm, location nonsubcapsular), and SU
      score were all significantly associated with positive NSLN status. However, on
      multivariate analysis, only the SU score was a significant independent predictor
      of NSLN status. No patient with an SU score of 0 had a positive NSLN.
      CONCLUSIONS: The SU score is predictive of NSLN status in patients with a
      positive SLND. Patients with an SU score of 0 are very unlikely to have positive
      NSLNs at CLND.

PMID- 12513957
TI  - Fifty tumor necrosis factor-based isolated limb perfusions for limb salvage in
      patients older than 75 years with limb-threatening soft tissue sarcomas and other
      extremity tumors.
AB  - BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor (TNF) and
      melphalan is highly effective in treating limb-threatening soft tissue sarcoma
      (STS) and other bulky tumors. Because of fear of TNF-associated toxicity, ILP
      with TNF is not offered to older patients in some cancer centers, although
      especially in older patients, every attempt to avoid an amputation that may end
      their independence must be considered. METHODS: Out of 306 TNF-based ILPs, 50
      ILPs were performed for limb salvage in 43 patients >75 years old (range, 75-91
      years): 29 STS and 14 melanoma patients. RESULTS: In the STS patients, a response
      rate of 76% and a limb-salvage rate of 76% were achieved; in the melanoma
      patients, a 100% response rate and a 93% limb-salvage rate were achieved. Local
      toxicity was mild. The three postoperative deaths that occurred in the total
      series of 306 TNF-based ILPs in Rotterdam (<1%) occurred in patients >75 years
      old after leakage-free perfusions and were not related to TNF but to extremely
      high-risk profiles in these three patients. CONCLUSIONS: Older patients should
      not be withheld a TNF-based ILP for limb salvage, because the procedure is safe
      and highly effective in these patients.

PMID- 12513958
TI  - Routine operative breast endoscopy during lumpectomy.
AB  - BACKGROUND: Lumpectomy for the management of breast cancer is commonly directed
      by mammography or ultrasound. We hypothesized that fluid-producing ducts would
      likely connect to the site of the known cancerous or precancerous lesion and that
      endoscopic evaluation might reveal unsuspected additional disease. METHODS: All
      women undergoing lumpectomy in a single surgeon's practice from January 2000 to
      August 2001 were evaluated for fluid production from the nipple at the time of
      lumpectomy. All fluid-producing ducts were cannulated and endoscoped with a 0.9
      mm Acueity microendoscope. RESULTS: Of the 201 patients (16 with atypical ductal
      hyperplasia, 52 with ductal carcinoma-in-situ, and 133 with stage 1 or 2 breast
      cancers), 150 (74.6%) could be successfully dilated and scoped. Additional
      lesions outside the anticipated lumpectomy were identified in 41% (n = 83) of
      cases. If successful, the chances for a positive margin for cancer decreased from
      23.5% to only 5.0%. Endoscopy proved to be a useful adjunct in this series of
      patients because it identified all cases of extensive intraductal component in
      early-stage breast cancer. CONCLUSIONS: Routine operative breast endoscopy can
      reduce the need for re-excision lumpectomy. It also finds substantially more
      cancerous and precancerous disease than anticipated by routine preoperative
      mammography and ultrasound.

PMID- 12513959
TI  - Accuracy of 11-gauge vacuum-assisted core biopsy of mammographic breast lesions.
AB  - BACKGROUND: Image-guided percutaneous biopsy has largely replaced excisional
      biopsy of mammographic lesions. Vacuum-assisted core biopsy has improved sampling
      of such lesions. The objectives of this study were to define the accuracy of the
      vacuum-assisted 11-gauge stereotactic core biopsy in sampling of atypical ductal
      hyperplasia (ADH) and ductal carcinoma in situ (DCIS) and to define histologic
      and mammographic features of target lesions, which predict sampling errors.
      METHODS: Between October 1996 and March 2000, 1341 patients underwent
      stereotactic 11-gauge vacuum-assisted biopsy. Patients with ADH or DCIS were
      encouraged to undergo excisional biopsy. RESULTS: Surgical excision of 37 ADH
      lesions revealed 5 missed DCIS lesions and 1 missed invasive cancer. Twelve of 91
      DCIS lesions were upstaged to invasive cancer upon excision. The underestimation
      rate was highest in patients with DCIS when the target lesion for biopsy was a
      zone of calcifications >1.5 cm. No correlation existed between the histologic
      features of DCIS lesions diagnosed by stereotactic biopsy and the presence of
      infiltrating disease on excision. CONCLUSIONS: Vacuum-assisted 11-gauge
      stereotactic core biopsy understages 13.2% and 13.5% of DCIS and ADH lesions,
      respectively. In patients with DCIS found by stereotactic biopsy, a target zone
      of calcifications >1.5 cm is associated with a higher underestimation rate of
      infiltrating disease.

PMID- 12513960
TI  - Significance of linear extent of breast carcinoma at surgical margin.
AB  - BACKGROUND: Our objective was to correlate the extent of margin positivity and
      the findings on re-excision specimens of infiltrating mammary carcinoma. METHODS:
      We selected 50 consecutive cases of infiltrating mammary carcinoma, including
      both infiltrating ductal carcinoma and infiltrating lobular carcinoma, with
      positive margins followed by re-excision. Margin positivity was defined as the
      presence of cancer at the inked margin. The extent of margin positivity was
      assessed by measuring the linear involvement of the inked margin by the
      carcinoma. RESULTS: Twenty-one of 50 cases (42%) showed positive findings on re
      excision, including either infiltrating carcinoma or carcinoma in situ or both.
      Nine of 14 cases (64%) with ductal carcinoma in situ or infiltrating ductal
      carcinoma on re-excision and 4 of 7 cases (57%) with lobular carcinoma in situ or
      infiltrating lobular carcinoma on re-excision had initial linear margins >1.0 cm,
      whereas 28 of 29 cases (96%) with negative findings on re-excision had initial
      linear margins <1.0 cm. CONCLUSIONS: Linear measurement of the inked margin
      involved by infiltrating mammary carcinoma can be used as a predictor of findings
      on re-excisions.

PMID- 12513961
TI  - Radiofrequency ablation in 447 complex unresectable liver tumors: lessons
      learned.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a promising technique for
      unresectable hepatic malignancies. We reviewed our RFA experience to identify
      variables affecting local recurrence. METHODS: Patients undergoing RFA between
      1997 and 2001 were reviewed for demographics, tumor size, pathology, diagnosis,
      recurrence, procedures, survival, and complications. RESULTS: The 447
      unresectable liver tumors were ablated in 198 procedures. The 153 patients
      averaged 61.9 years of age and 1.25 RFA procedures per patient. Follow-up
      averaged 11 months. Serial ablations were performed in 28 patients, 8 of whom are
      without evidence of disease. Tumors were most commonly carcinomas of colorectal,
      hepatocellular, breast, and melanoma histologies. Colorectal carcinomas and
      hepatomas individually recurred more frequently than all other tumor types
      combined in univariate analyses (P =.009 and P =.008, respectively). Patients
      with multiple tumors ablated recurred significantly more frequently (P =.001).
      Size was also significant in univariate and multivariate analyses (P =.0032 and
      <.0001, respectively). Eighteen patients experienced 36 complications.
      CONCLUSIONS: Size has the highest correlation with local recurrence, but multiple
      tumors and pathology may also predict local recurrence risk. Large, complex
      lesions can be safely serially ablated, but because of morbidity and recurrence,
      RFA should not replace resection as the primary treatment of resectable liver
      tumors.

PMID- 12513962
TI  - Positron emission tomography affects surgical management in recurrent colorectal
      cancer patients.
AB  - BACKGROUND: We determined the effect of positron emission tomography (PET) on
      surgical decision-making in patients with metastatic or recurrent colorectal
      cancer. METHODS: A total of 114 patients with advanced colorectal cancer were
      imaged with computed tomography (CT) and PET scans. The PET and CT scans were
      independently interpreted before surgery and recorded. RESULTS: Forty-two of the
      114 patients had resectable disease on the basis of CT. PET altered therapy in 17
      (40%) of these 42 patients on the basis of the following results: extrahepatic
      disease (n = 9), bilobar involvement (n = 3), thoracic involvement (n = 5),
      retroperitoneal lymphadenopathy (n = 2), bone involvement (n = 1), and
      supraclavicular disease (n = 1). In 25 patients with liver metastases only, PET
      found additional disease in 18 (72%), extrahepatic disease in 11, chest disease
      in 13, retroperitoneal lymphadenopathy in 4, and bone disease in 3. In five
      patients, both scans underestimated small-volume peritoneal metastases discovered
      at laparotomy. CONCLUSIONS: PET altered therapy in 40% of patients. In patients
      with isolated liver involvement, 72% had more extensive disease that precluded
      surgical resection. PET scans should be used in the management of patients with
      recurrent colorectal cancer who are being considered for potentially curative
      surgery.

PMID- 12513963
TI  - The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes
      examined.
AB  - BACKGROUND: T3N0 colon cancer is the target of many adjuvant studies. Very few
      studies have examined the relationship of the number of lymph nodes examined to
      the prognosis of this stage. We examined data from the National Cancer Data Base
      (NCDB) to determine whether the number of examined lymph nodes is prognostic for
      T3N0 colon cancer. METHODS: A total of 35,787 prospectively collected cases of
      T3N0 colon cancer that were surgically treated and pathologically reported from
      1985 to 1991 to the NCDB as T3N0M0 were analyzed. RESULTS: The 5-year relative
      survival rate for T3N0M0 colon cancer varied from 64% if 1 or 2 lymph nodes were
      examined to 86% if > 25 lymph nodes were examined. Three strata of lymph nodes (1
      7, 8-12, and > or = 13) distinguished significantly different observed 5-year
      survival rates. CONCLUSIONS: These results demonstrate that the prognosis of T3N0
      colon cancer is dependent on the number of lymph nodes examined. A minimum of 13
      lymph nodes should be examined to label a T3 colon cancer as node negative. These
      data suggest that adjuvant trials for T3N0 colon cancer should stratify according
      to the number of lymph nodes examined.

PMID- 12513964
TI  - Symptom control in patients with locally recurrent rectal cancer.
AB  - BACKGROUND: Although resection of locally recurrent rectal cancer has been
      associated with improved survival, clinical outcomes after such repeat surgery
      have been incompletely characterized. METHODS: From 1997 to 1999, 105 consecutive
      patients requiring repeat surgery for locally recurrent rectal cancer were
      identified. Patients were observed for a minimum of 2 years or until death.
      RESULTS: An operation was performed with palliative intent in 23% of patients.
      Before repeat surgery, 79% of the palliative-intent patients had symptoms: 21%
      bleeding, 42% obstruction, and 21% pain. After repeat surgery with palliative
      intent, improvement was noted in 40% with bleeding, 70% with obstruction, and 20%
      with pain. Additional or recurrent symptoms were noted in 87% during follow-up.
      Seventy-seven percent of patients had an operation with nonpalliative intent.
      Before repeat surgery, 57% of nonpalliative patients had symptoms, with 32%
      experiencing bleeding, 11% obstruction, and 19% pain. After repeat surgery with
      nonpalliative intent, initial improvement was noted in 88% with bleeding, 78%
      with obstruction, and 40% with pain. During follow-up, symptoms arose in 37% of
      the initially asymptomatic patients, and additional or recurrent symptoms were
      seen in 63% of those previously symptomatic. CONCLUSIONS: Although symptomatic
      relief is associated with repeat surgery, the recurrence or development of
      alternate symptoms makes a completely asymptomatic clinical course uncommon.

PMID- 12513965
TI  - Adequacy of 1-cm distal margin after restorative rectal cancer resection with
      sharp mesorectal excision and preoperative combined-modality therapy.
AB  - BACKGROUND: Preoperative combined-modality therapy (CMT) for rectal cancer allows
      a sphincter-sparing procedure in some individuals who would otherwise require an
      abdominoperineal resection. To further define the subset of rectal cancer
      patients suitable for this approach, we determined the adequacy of a distal
      margin of < or = 1 cm in patients with locally advanced rectal cancer requiring
      preoperative CMT. METHODS: Ninety-four consecutive patients, status post curative
      low anterior resection for rectal cancer after preoperative CMT, were identified
      from the prospective Colorectal Service Database. Distal margin length, tumor
      grade, tumor-node-metastasis stage, presence of lymphovascular and perineural
      invasion, and tumor distance from the anal verge were examined for their effect
      on recurrence and survival. Median follow-up was 44 months. RESULTS: Distal
      margin length ranged from.1 to 9.5 cm (median, 2.0 cm) and did not correlate with
      local recurrence (hazard ratio, 1.1; P =.34) or recurrence-free survival (hazard
      ratio, 1.1; P =.29) by univariate analysis. Kaplan-Meier estimates of recurrence
      free survival and local recurrence at 3 years for the < or = 1 cm versus >1 cm
      and the < ore = 2 cm versus > 2 cm groups were not significantly different.
      Groups were well matched for other clinicopathologic variables. CONCLUSIONS: Our
      data suggest that for patients with locally advanced rectal cancer undergoing
      resection and preoperative CMT, distal margins < or = 1 cm do not seem to
      compromise oncological outcome.

PMID- 12513966
TI  - Positron emission mammography: initial clinical results.
AB  - BACKGROUND: Evaluation of high-risk mammograms represents an enormous clinical
      challenge. Functional breast imaging coupled with mammography (positron emission
      mammography [PEM]) could improve imaging of such lesions. A prospective study was
      performed using PEM in women scheduled for stereotactic breast biopsy. METHODS:
      Patients were recruited from the surgical clinic. Patients were injected with 10
      mCi of 2-[18F] fluorodeoxyglucose. One hour later, patients were positioned on
      the stereotactic biopsy table, imaged with a PEM scanner, and a stereotactic
      biopsy was performed. Imaging was reviewed and compared with pathologic results.
      RESULTS: There were 18 lesions in 16 patients. PEM images were analyzed by
      drawing a region of interest at the biopsy site and comparing the count density
      in the region of interest with the background. A lesion-to-background ratio >2.5
      appeared to be a robust indicator of malignancy and yielded a sensitivity of 86%,
      specificity of 91%, and overall diagnostic accuracy of 89%. No adverse events
      were associated with the PEM imaging. CONCLUSIONS: The data show that PEM is
      safe, feasible, and has an encouraging accuracy rate in this initial experience.
      Lesion-to-background ratios >2.5 were found to be a useful threshold value for
      identifying positive (malignant) results. This study supports the further
      development of PEM.

PMID- 12513967
TI  - Breast and gastric cancer: comparing what we learn.

PMID- 12513968
TI  - Calcium-independent contraction and sensitization of airway smooth muscle by p21
      activated protein kinase.
AB  - In Triton-skinned phasic ileal smooth muscle, constitutively active recombinant
      p21-activated kinase (PAK3) has been shown to induce Ca(2+)-independent
      contraction, which is accompanied by phosphorylation of caldesmon and desmin (Van
      Eyk JE, Arrell DK, Foster DB, Strauss JD, Heinonen TY, Furmaniak-Kazmierczak E,
      Cote GP, and Mak AS. J Biol Chem 273: 23433-23439, 1998). In the present study,
      we investigated whether PAK has a broad impact on smooth muscle in general by
      testing the hypothesis that PAK induces Ca(2+)-independent contractions and/or
      Ca(2+) sensitization in tonic airway smooth muscle and that the process is
      mediated via phosphorylation of caldesmon. In the absence of Ca(2+) (pCa > 9),
      constitutively active glutathione-S-transferase-murine PAK3 (GST-mPAK3) caused
      force generation of Triton-skinned canine tracheal smooth muscle (TSM) fibers to
      approximately 40% of the maximal force generated by Ca(2+) at pCa 4.4. In
      addition, GST-mPAK3 enhanced Ca(2+) sensitivity of contraction by increasing
      force generation by 80% at intermediate Ca(2+) concentrations (pCa 6.2), whereas
      it had no effect at pCa 4.4. Catalytically inactive GST-mPAK3(K297R) had no
      effect on force production. Using antibody against one of the PAK-phosphorylated
      sites (Ser(657)) on caldesmon, we showed that a basal level of phosphorylation of
      caldesmon occurs at this site in skinned TSM and that PAK-induced contraction was
      accompanied by a significant increase in the level of phosphorylation. Western
      blot analyses show that PAK1 is the predominant PAK isoform expressed in murine,
      rat, canine, and porcine TSM. We conclude that PAK causes Ca(2+)-independent
      contractions and produces Ca(2+) sensitization of skinned phasic and tonic smooth
      muscle, which involves an incremental increase in caldesmon phosphorylation.

PMID- 12513969
TI  - Transfection of lung cells in vitro and in vivo: effect of antioxidants and
      intraliposomal bFGF.
AB  - We hypothesized that constitutive formation of reactive oxygen species by
      respiratory cells is a barrier to gene transfer when liposome-DNA complexes are
      used, by contributing to rapid degradation of plasmid DNA. When plasmid DNA is
      complexed to liposomes it is protected against H(2)O(2)-mediated degradation but
      not that mediated by the hydroxyl radical. Treatment of distal rat fetal lung
      epithelial cells (RFL(19)Ep) with the vitamin E analog Trolox (50 microM) reduced
      intracellular plasmid degradation. Both Trolox (50 microM) and an iron chelator,
      phenanthroline (0.1 microM), significantly increased transgene expression in
      RFL(19)Ep approximately twofold, consistent with a hydroxyl radical-mediated
      inhibition of transgene expression. When basic fibroblast growth factor (bFGF; 20
      ng/ml), a growth factor with antioxidant properties, was included within
      liposomes, we observed a significantly greater enhancement of RFL(19)Ep transgene
      expression (approximately 2-fold) over that seen with Trolox or phenanthroline.
      Inclusion of bFGF within liposomes also significantly enhanced (approximately 4
      fold) transgene expression in mice following intratracheal instillation.

PMID- 12513970
TI  - A postgenomic appraisal of osmotolerance in Listeria monocytogenes.

PMID- 12513971
TI  - Nodulation gene regulation in Bradyrhizobium japonicum: a unique integration of
      global regulatory circuits.

PMID- 12513972
TI  - Bacterial competition for human nasal cavity colonization: role of Staphylococcal
      agr alleles.
AB  - We examined the bacterial aerobic nasal flora of 216 healthy volunteers to
      identify potential competitive interactions among different species, with special
      emphasis on the influence of staphylococcal agr alleles. The Staphylococcus
      aureus colonization rate correlated negatively with the rate of colonization by
      Corynebacterium spp. and non-aureus staphylococci, especially S. epidermidis,
      suggesting that both Corynebacterium spp. and S. epidermidis antagonize S. aureus
      colonization. Most of the S. aureus and S. epidermidis isolates were agr typed by
      a PCR method. Only one S. aureus agr (agr(Sa)) allele was detected in each
      carrier. Multiple logistic regression of the two most prevalent agr(Sa) alleles
      (agr-1(Sa) and agr-2(Sa)) and the three S. epidermidis agr (agr(Se)) alleles
      showed a specific influence of the agr system. The results of this model did not
      support conclusions drawn from previous in vitro agr-specific cross-inhibition
      experiments. Our findings suggest that the agr alleles, which are strongly linked
      to the bacterial genetic background, may simply be associated with common
      biological properties--including mediators of bacterial interference--in the
      strains that bear them.

PMID- 12513973
TI  - Induction of sucrose utilization genes from Bifidobacterium lactis by sucrose and
      raffinose.
AB  - The probiotic organism Bifidobacterium lactis was isolated from a yoghurt starter
      culture with the aim of analyzing its use of carbohydrates for the development of
      prebiotics. A sucrose utilization gene cluster of B. lactis was identified by
      complementation of a gene library in Escherichia coli. Three genes, encoding a
      sucrose phosphorylase (ScrP), a GalR-LacI-type transcriptional regulator (ScrR),
      and a sucrose transporter (ScrT), were identified by sequence analysis. The scrP
      gene was expressed constitutively from its own promoter in E. coli grown in
      complete medium, and the strain hydrolyzed sucrose in a reaction that was
      dependent on the presence of phosphates. Primer extension experiments with scrP
      performed by using RNA isolated from B. lactis identified the transcriptional
      start site 102 bp upstream of the ATG start codon, immediately adjacent to a
      palindromic sequence resembling a regulator binding site. In B. lactis, total
      sucrase activity was induced by the presence of sucrose, raffinose, or
      oligofructose in the culture medium and was repressed by glucose. RNA analysis of
      the scrP, scrR, and scrT genes in B. lactis indicated that expression of these
      genes was influenced by transcriptional regulation and that all three genes were
      similarly induced by sucrose and raffinose and repressed by glucose. Analysis of
      the sucrase activities of deletion constructs in heterologous E. coli indicated
      that ScrR functions as a positive regulator.

PMID- 12513974
TI  - Bacillus anthracis diverges from related clades of the Bacillus cereus group in
      16S-23S ribosomal DNA intergenic transcribed spacers containing tRNA genes.
AB  - Mung bean nuclease treatment of 16S-23S ribosomal DNA intergenic transcribed
      spacers (ITS) amplified from several strains of the six species of the Bacillus
      cereus group showed that B. anthracis Davis TE702 and B. mycoides G2 have other
      intermediate fragments in addition to the 220- and 550-bp homoduplex fragments
      typical of the B. cereus group. Long and intermediate homoduplex ITS fragments
      from strains Davis TE702 and G2 and from another 19 strains of the six species
      were sequenced. Two main types of ITS were found, either with two tRNA genes
      (tRNA(Ile) and tRNA(Ala)) or without any at all. Strain Davis TE702 harbors an
      additional ITS with a single tRNA gene, a hybrid between the tRNA(Ile) and
      tRNA(Ala) genes, suggesting that a recombination event rather than a deletion
      generated the single tDNA-containing ITS. Strain G2 showed an additional ITS of
      intermediate length with no tDNA and no similarity to other known sequences.
      Neighbor-joining analysis of tDNA-containing long ITS indicated that B. cereus
      and B. thuringiensis represent a single clade. Three signature sequences
      discriminated B. anthracis from B. cereus and B. thuringiensis, indicating that
      the anthrax agent started evolving separately from the related clades of the B.
      cereus group. B. mycoides and B. weienstephanensis were very closely related,
      while B. pseudomycoides appeared the most distant species.

PMID- 12513975
TI  - Use of real-time quantitative PCR for the analysis of phiLC3 prophage stability
      in lactococci.
AB  - Bacteriophages are a common and constant threat to proper milk fermentation. It
      has become evident that lysogeny is widespread in lactic acid bacteria, and in
      this work the temperate lactococcal bacteriophage phi LC3 was used as a model to
      study prophage stability in lactococci. The stability was analyzed in six phi LC3
      lysogenic Lactococcus lactis subsp. cremoris host strains when they were growing
      at 15 and 30 degrees C. In order to perform these analyses, a real-time PCR assay
      was developed. The stability of the phi LC3 prophage was found to vary with the
      growth phase of its host L. lactis IMN-C1814, in which the induction rate
      increased during the exponential growth phase and reached a maximum level when
      the strain was entering the stationary phase. The maximum spontaneous induction
      frequency of the phi LC3 prophage varied between 0.32 and 9.1% (28-fold) in the
      six lysogenic strains. No correlation was observed between growth rates of the
      host cells and the spontaneous prophage induction frequencies. Furthermore, the
      level of extrachromosomal phage DNA after induction of the prophage varied
      between the strains (1.9 to 390%), and the estimated burst sizes varied up to
      eightfold. These results show that the host cells have a significant impact on
      the lytic and lysogenic life styles of temperate bacteriophages. The present
      study shows the power of the real-time PCR technique in the analysis of temperate
      phage biology and will be useful in work to reveal the impact of temperate phages
      and lysogenic bacteria in various ecological fields.

PMID- 12513976
TI  - Recombinant environmental libraries provide access to microbial diversity for
      drug discovery from natural products.
AB  - To further explore possible avenues for accessing microbial biodiversity for drug
      discovery from natural products, we constructed and screened a 5,000-clone
      "shotgun" environmental DNA library by using an Escherichia coli-Streptomyces
      lividans shuttle cosmid vector and DNA inserts from microbes derived directly
      (without cultivation) from soil. The library was analyzed by several means to
      assess diversity, genetic content, and expression of heterologous genes in both
      expression hosts. We found that the phylogenetic content of the DNA library was
      extremely diverse, representing mostly microorganisms that have not been
      described previously. The library was screened by PCR for sequences similar to
      parts of type I polyketide synthase genes and tested for the expression of new
      molecules by screening of live colonies and cell extracts. The results revealed
      new polyketide synthase genes in at least eight clones. In addition, at least
      five additional clones were confirmed by high-pressure liquid chromatography
      analysis and/or biological activity to produce heterologous molecules. These data
      reinforce the idea that exploiting previously unknown or uncultivated
      microorganisms for the discovery of novel natural products has potential value
      and, most importantly, suggest a strategy for developing this technology into a
      realistic and effective drug discovery tool.

PMID- 12513977
TI  - ACEI of Trichoderma reesei is a repressor of cellulase and xylanase expression.
AB  - We characterized the effect of deletion of the Trichoderma reesei (Hypocrea
      jecorina) ace1 gene encoding the novel cellulase regulator ACEI that was isolated
      based on its ability to bind to and activate in vivo in Saccharomyces cerevisiae
      the promoter of the main cellulase gene, cbh1. Deletion of ace1 resulted in an
      increase in the expression of all the main cellulase genes and two xylanase genes
      in sophorose- and cellulose-induced cultures, indicating that ACEI acts as a
      repressor of cellulase and xylanase expression. Growth of the strain with a
      deletion of the ace1 gene on different carbon sources was analyzed. On cellulose
      based medium, on which cellulases are needed for growth, the Deltaace1 strain
      grew better than the host strain due to the increased cellulase production. On
      culture media containing sorbitol as the sole carbon source, the growth of the
      strain with a deletion of the ace1 gene was severely impaired, suggesting that
      ACEI regulates expression of other genes in addition to cellulase and xylanase
      genes. A strain with a deletion of the ace1 gene and with a deletion of the ace2
      gene coding for the cellulase and xylanase activator ACEII expressed cellulases
      and xylanases similar to the Deltaace1 strain, indicating that yet another
      activator regulating cellulase and xylanase promoters was present.

PMID- 12513978
TI  - Enzymatic conversion of averufin to hydroxyversicolorone and elucidation of a
      novel metabolic grid involved in aflatoxin biosynthesis.
AB  - The pathway from averufin (AVR) to versiconal hemiacetal acetate (VHA) in
      aflatoxin biosynthesis was investigated by using cell-free enzyme systems
      prepared from Aspergillus parasiticus. When (1'S,5'S)-AVR was incubated with a
      cell extract of this fungus in the presence of NADPH, versicolorin A and
      versicolorin B (VB), as well as other aflatoxin pathway intermediates, were
      formed. When the same substrate was incubated with the microsome fraction and
      NADPH, hydroxyversicolorone (HVN) and VHA were formed. However, (1'R,5'R)-AVR did
      not serve as the substrate. In cell-free experiments performed with the cytosol
      fraction and NADPH, VHA, versicolorone (VONE), and versiconol acetate (VOAc) were
      transiently produced from HVN in the early phase, and then VB and versiconol
      (VOH) accumulated later. Addition of dichlorvos (dimethyl 2,2
      dichlorovinylphosphate) to the same reaction mixture caused transient formation
      of VHA and VONE, followed by accumulation of VOAc, but neither VB nor VOH was
      formed. When VONE was incubated with the cytosol fraction in the presence of
      NADPH, VOAc and VOH were newly formed, whereas the conversion of VOAc to VOH was
      inhibited by dichlorvos. The purified VHA reductase, which was previously
      reported to catalyze the reaction from VHA to VOAc, also catalyzed conversion of
      HVN to VONE. Separate feeding experiments performed with A. parasiticus NIAH-26
      along with HVN, VONE, and versicolorol (VOROL) demonstrated that each of these
      substances could serve as a precursor of aflatoxins. Remarkably, we found that
      VONE and VOROL had ring-opened structures. Their molecular masses were 386 and
      388 Da, respectively, which were 18 Da greater than the molecular masses
      previously reported. These data demonstrated that two kinds of reactions are
      involved in the pathway from AVR to VHA in aflatoxin biosynthesis: (i) a reaction
      from (1'S,5'S)-AVR to HVN, catalyzed by the microsomal enzyme, and (ii) a new
      metabolic grid, catalyzed by a new cytosol monooxygenase enzyme and the
      previously reported VHA reductase enzyme, composed of HVN, VONE, VOAc, and VHA. A
      novel hydrogenation-dehydrogenation reaction between VONE and VOROL was also
      discovered.

PMID- 12513979
TI  - Hydrogenotrophic methanogenesis by moderately acid-tolerant methanogens of a
      methane-emitting acidic peat.
AB  - The emission of methane (1.3 mmol of CH(4) m(-2) day(-1)), precursors of
      methanogenesis, and the methanogenic microorganisms of acidic bog peat (pH 4.4)
      from a moderately reduced forest site were investigated by in situ measurements,
      microcosm incubations, and cultivation methods, respectively. Bog peat produced
      CH(4) (0.4 to 1.7 micro mol g [dry wt] of soil(-1) day(-1)) under anoxic
      conditions. At in situ pH, supplemental H(2)-CO(2), ethanol, and 1-propanol all
      increased CH(4) production rates while formate, acetate, propionate, and butyrate
      inhibited the production of CH(4); methanol had no effect. H(2)-dependent
      acetogenesis occurred in H(2)-CO(2)-supplemented bog peat only after extended
      incubation periods. Nonsupplemented bog peat initially produced small amounts of
      H(2) that were subsequently consumed. The accumulation of H(2) was stimulated by
      ethanol and 1-propanol or by inhibiting methanogenesis with bromoethanesulfonate,
      and the consumption of ethanol was inhibited by large amounts of H(2); these
      results collectively indicated that ethanol- or 1-propanol-utilizing bacteria
      were trophically associated with H(2)-utilizing methanogens. A total of 10(9)
      anaerobes and 10(7) hydrogenotrophic methanogens per g (dry weight) of bog peat
      were enumerated by cultivation techniques. A stable methanogenic enrichment was
      obtained with an acidic, H(2)-CO(2)-supplemented, fatty acid-enriched defined
      medium. CH(4) production rates by the enrichment were similar at pH 4.5 and 6.5,
      and acetate inhibited methanogenesis at pH 4.5 but not at pH 6.5. A total of 27
      different archaeal 16S rRNA gene sequences indicative of Methanobacteriaceae,
      Methanomicrobiales, and Methanosarcinaceae were retrieved from the highest CH(4)
      positive serial dilutions of bog peat and methanogenic enrichments. A total of 10
      bacterial 16S rRNA gene sequences were also retrieved from the same dilutions and
      enrichments and were indicative of bacteria that might be responsible for the
      production of H(2) that could be used by hydrogenotrophic methanogens. These
      results indicated that in this acidic bog peat, (i) H(2) is an important
      substrate for acid-tolerant methanogens, (ii) interspecies hydrogen transfer is
      involved in the degradation of organic carbon, (iii) the accumulation of
      protonated volatile fatty acids inhibits methanogenesis, and (iv) methanogenesis
      might be due to the activities of methanogens that are phylogenetic members of
      the Methanobacteriaceae, Methanomicrobiales, and Methanosarcinaceae.

PMID- 12513980
TI  - Intergeneric conjugation in Streptomyces peucetius and Streptomyces sp. strain
      C5: chromosomal integration and expression of recombinant plasmids carrying the
      chiC gene.
AB  - Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to
      Streptomyces circumvents problems such as host-controlled restriction and
      instability of foreign DNA during the transformation of Streptomyces protoplasts.
      The anthracycline antibiotic-producing strains Streptomyces peucetius and
      Streptomyces sp. strain C5 were transformed using E. coli ET12567(pUZ8002) as a
      conjugal donor. When this donor species, carrying pSET152, was mated with
      Streptomyces strains, the resident plasmid was mobilized to the recipient and the
      transferred DNA was also integrated into the recipient chromosome. Analysis of
      the exconjugants showed stable integration of the plasmid at a single chromosomal
      site (attB) of the Streptomyces genome. The DNA sequence of the chromosomal
      integration site was determined and shown to be conserved. However, the core
      sequence, where the crossover presumably occurred in C5 and S. peucetius, is TTC.
      These results also showed that the phiC31 integrative recombination is active and
      the phage attP site is functional in S. peucetius as well as in C5. The
      efficiency and specificity of phiC31-mediated site-specific integration of the
      plasmid in the presence of a 3.7-kb homologous DNA sequence indicates that
      integrative recombination is preferred under these conditions. The integration of
      plasmid DNA did not affect antibiotic biosynthesis or biosynthesis of essential
      amino acids. Integration of a single copy of a mutant chiC into the wild-type S.
      peucetius chromosome led to the production of 30-fold more chitinase.

PMID- 12513981
TI  - Enterococci as indicators of Lake Michigan recreational water quality: comparison
      of two methodologies and their impacts on public health regulatory events.
AB  - The frequency of poor-water-quality advisories issued in Milwaukee and Racine,
      Wisconsin, in the absence of identifiable sources of contamination brought into
      question the reliability of the present indicator organism, Escherichia coli.
      Enteroccoci have been suggested as an alternative to E. coli for freshwater
      monitoring due to their direct correlation to swimmer-associated gastroenteritis.
      The purpose of this research was threefold: (i) to explore enterococci as an
      alternative to E. coli for monitoring freshwater Lake Michigan beaches, (ii) to
      evaluate the impact of the two indicators on regulatory decisions, and (iii) to
      compare membrane filtration m-enterococcus agar with indoxyl-beta-D-glucoside to
      a chemical substrate technique (Enterolert) for the recovery of enterococci.
      Recreational water samples from Milwaukee (n = 305) and Racine (n = 153) were
      analyzed for the enumeration of E. coli and enterococci using IDEXX Colilert-18
      and Enterolert. Correlation between the indicators was low (R(2) = 0.60 and
      0.69). Based on U.S. Environmental Protection Agency bacterial indicator
      threshold levels of risk for full body immersion, using enterococci would have
      resulted in 56 additional unsafe-recreational-water-quality advisories compared
      to the total from using E. coli and the substrate-based methods. A comparison of
      the two enterococcal methods (n = 124) yielded similar results (R(2) = 0.62).
      This was further confounded by the frequent inability to verify enterococci from
      those wells producing fluorescence by the defined substrate test using
      conventional microbiological methods. These results suggest that further research
      is necessary regarding the use of defined substrate technology interchangeably
      with the U.S. Environmental Protection Agency-approved membrane filtration test
      for the detection of enterococci from fresh surface water.

PMID- 12513982
TI  - Improved understanding of the bacterial vaginal microbiota of women before and
      after probiotic instillation.
AB  - The vaginal bacterial microbiota of 19 premenopausal women was examined by PCR
      denaturing gradient gel electrophoresis (DGGE) and sequencing of the V2-V3 region
      of the 16S rRNA gene. Ten of the women were studied further to investigate the
      effect and persistence of vaginally inserted capsules containing viable
      lactobacilli. PCR-DGGE indicated that most subjects had a microbiota represented
      by one to three dominant DNA fragments. Analysis of these fragments revealed that
      79% of the women possessed sequences with high levels of similarity to
      Lactobacillus species sequences. Sequences homologous to Lactobacillus iners
      sequences were the most common and were detected in 42% of the women tested.
      Alteration of the vaginal microbiota could be detected by PCR-DGGE in several
      women after the instillation of lactobacilli. Additionally, randomly amplified
      polymorphic DNA analysis of lactobacilli isolated from selective media
      demonstrated that the exogenous strains could be detected for up to 21 days in
      some subjects. This study demonstrates that non-culture-based techniques, such as
      PCR-DGGE, are useful adjuncts for studies of the vaginal microbiota.

PMID- 12513983
TI  - Development and application of different methods for the detection of Toxoplasma
      gondii in water.
AB  - Two methods, centrifugation and flocculation, were evaluated to determine their
      efficiencies of recovery of Toxoplasma gondii oocysts from contaminated water
      samples. Demineralized and tap water replicates were inoculated with high numbers
      of sporulated or unsporulated T. gondii oocysts (1 x 10(5) and 1 x 10(4)
      oocysts). The strain, age, and concentration of the seeded oocysts were recorded.
      Oocysts were recovered either by centrifugation of the contaminated samples at
      various g values or by flocculation with two coagulants, Fe(2)(SO(4))(3) and
      Al(2)(SO(4))(3). The recovery rates were determined with the final pellets by
      phase-contrast microscopy. Sporulated oocysts were recovered more effectively by
      flocculation with Al(2)(SO(4))(3) (96.5% +/- 21.7%) than by flocculation with
      Fe(2)(SO(4))(3) (93.1% +/- 8.1%) or by centrifugation at 2,073 x g (82.5% +/-
      6.8%). For the unsporulated oocysts, flocculation with Fe(2)(SO(4))(3) was more
      successful (100.3% +/- 26.9%) than flocculation with Al(2)(SO(4))(3) (90.4% +/-
      19.1%) or centrifugation at 2,565 x g (97.2% +/- 12.5%). The infectivity of the
      sporulated oocysts recovered by centrifugation was confirmed by seroconversion of
      all inoculated mice 77 days postinfection. These data suggest that sporulated
      Toxoplasma oocysts purified by methods commonly used for waterborne pathogens
      retain their infectivity after mechanical treatment and are able to induce
      infections in mammals. This is the first step in developing a systematic approach
      for the detection of Toxoplasma oocysts in water.

PMID- 12513984
TI  - Isolation and characterization of a sulfur-oxidizing chemolithotroph growing on
      crude oil under anaerobic conditions.
AB  - Molecular approaches have shown that a group of bacteria (called cluster 1
      bacteria) affiliated with the epsilon subclass of the class Proteobacteria
      constituted major populations in underground crude-oil storage cavities. In order
      to unveil their physiology and ecological niche, this study isolated bacterial
      strains (exemplified by strain YK-1) affiliated with the cluster 1 bacteria from
      an oil storage cavity at Kuji in Iwate, Japan. 16S rRNA gene sequence analysis
      indicated that its closest relative was Thiomicrospira denitrificans (90%
      identity). Growth experiments under anaerobic conditions showed that strain YK-1
      was a sulfur-oxidizing obligate chemolithotroph utilizing sulfide, elemental
      sulfur, thiosulfate, and hydrogen as electron donors and nitrate as an electron
      acceptor. Oxygen also supported its growth only under microaerobic conditions.
      Strain YK-1 could not grow on nitrite, and nitrite was the final product of
      nitrate reduction. Neither sugars, organic acids (including acetate), nor
      hydrocarbons could serve as carbon and energy sources. A typical stoichiometry of
      its energy metabolism followed an equation: S(2-) + 4NO(3)(-) --> SO(4)(2-) +
      4NO(2)(-) (Delta G(0) = -534 kJ mol(-1)). In a difference from other anaerobic
      sulfur-oxidizing bacteria, this bacterium was sensitive to NaCl; growth in medium
      containing more than 1% NaCl was negligible. When YK-1 was grown anaerobically in
      a sulfur-depleted inorganic medium overlaid with crude oil, sulfate was produced,
      corresponding to its growth. On the contrary, YK-1 could not utilize crude oil as
      a carbon source. These results suggest that the cluster 1 bacteria yielded energy
      for growth in oil storage cavities by oxidizing petroleum sulfur compounds. Based
      on its physiology, ecological interactions with other members of the groundwater
      community are discussed.

PMID- 12513985
TI  - Oxygen consumption by anaerobic Saccharomyces cerevisiae under enological
      conditions: effect on fermentation kinetics.
AB  - The anaerobic growth of the yeast Saccharomyces cerevisiae normally requires the
      addition of molecular oxygen, which is used to synthesize sterols and unsaturated
      fatty acids (UFAs). A single oxygen pulse can stimulate enological fermentation,
      but the biochemical pathways involved in this phenomenon remain to be elucidated.
      We showed that the addition of oxygen (0.3 to 1.5 mg/g [dry mass] of yeast) to a
      lipid-depleted medium mainly resulted in the synthesis of the sterols and UFAs
      required for cell growth. However, the addition of oxygen during the stationary
      phase in a medium containing excess ergosterol and oleic acid increased the
      specific fermentation rate, increased cell viability, and shortened the
      fermentation period. Neither the respiratory chain nor de novo protein synthesis
      was required for these medium- and long-term effects. As de novo lipid synthesis
      may be involved in ethanol tolerance, we studied the effect of oxygen addition on
      sterol and UFA auxotrophs (erg1 and ole1 mutants, respectively). Both mutants
      exhibited normal anaerobic fermentation kinetics. However, only the ole1 mutant
      strain responded to the oxygen pulse during the stationary phase, suggesting that
      de novo sterol synthesis is required for the oxygen-induced increase of the
      specific fermentation rate. In conclusion, the sterol pathway appears to
      contribute significantly to the oxygen consumption capacities of cells under
      anaerobic conditions. Nevertheless, we demonstrated the existence of alternative
      oxygen consumption pathways that are neither linked to the respiratory chain nor
      linked to heme, sterol, or UFA synthesis. These pathways dissipate the oxygen
      added during the stationary phase, without affecting the fermentation kinetics.

PMID- 12513986
TI  - High pH during trisodium phosphate treatment causes membrane damage and
      destruction of Salmonella enterica serovar enteritidis.
AB  - Trisodium phosphate (TSP) is now widely used during the processing of poultry and
      red meats, but the mechanism whereby it inactivates gram-negative bacteria such
      Salmonella spp. remains unclear. Thus, Salmonella enterica serovar Enteritidis
      (ATCC 4931) cells were treated with different concentrations of TSP (1.5, 2.0,
      and 2.5% [wt/vol]) and compared with (i) cells treated with the same pH as the
      TSP treatments (pH 10.0, 10.5, and 11.0, respectively) and (ii) cells treated
      with different concentrations of TSP (1.5, 2.0, and 2.5% [wt/vol]) adjusted to a
      pH of 7.0 +/- 0.2 (mean +/- standard deviation). Cell viability, loss of membrane
      integrity, cellular leakage, release of lipopolysaccharides, and cell morphology
      were accordingly examined and quantified under the above treatment conditions.
      Exposure of serovar Enteritidis cells to TSP or equivalent alkaline pH resulted
      in the loss of cell viability and membrane integrity in a TSP concentration- or
      alkaline pH-dependent manner. In contrast, cells treated with different
      concentrations of TSP whose pH was adjusted to 7.0 did not show any loss of cell
      viability or membrane integrity. A 30-min pretreatment with 1.0 mM EDTA
      significantly enhanced the loss of membrane integrity only when followed by TSP
      or alkaline pH treatments. Measuring the absorbance at 260 nm, agarose gel
      electrophoresis, Bradford assay, and Tricine-sodium dodecyl sulfate gel
      electrophoresis of filtrates of treated cell suspensions revealed considerable
      release of DNA, proteins, and lipopolysaccharides compared to controls and pH 7.0
      TSP treatments. Electron microscopic examination of TSP- or alkaline pH-treated
      cells showed disfigured cell surface topology and wrinkled appearance and showed
      evidence of a TSP concentration- and pH-dependent disruption of the cytoplasmic
      and outer membranes. These results demonstrate that TSP treatment permeabilizes
      and disrupts the cytoplasmic and outer membranes of serovar Enteritidis cells
      because of the alkaline pH, which in turn leads to release of intracellular
      contents and eventual cell death.

PMID- 12513987
TI  - Genetic diversity and spoilage potentials among Pseudomonas spp. isolated from
      fluid milk products and dairy processing plants.
AB  - Degradation of milk components through various enzymatic activities associated
      with the contamination of dairy products by Pseudomonas spp. can reduce the shelf
      life of processed milk. Reliable methods for differentiating among Pseudomonas
      spp. strains are necessary to identify and eliminate specific sources of
      bacterial contamination from dairy processing systems. To that end, we assessed
      the genetic diversity and dairy product spoilage potentials among a total of 338
      Pseudomonas spp. isolates from raw and pasteurized milk and from environmental
      samples collected from four dairy processing plants. The majority of isolates
      were identified as P. fluorescens and P. putida by API 20 NE. A total of 42
      different ribotype patterns were identified among a subset of 81 isolates. The
      presence of many different ribotypes within this collection indicates high
      genetic diversity among the isolates and suggests multiple origins of
      contamination within the processing plant and in dairy products. The
      extracellular enzyme activity patterns among Pseudomonas isolates appeared to be
      associated with ribotypes. Isolates with the same ribotype frequently had the
      same extracellular protease, lecithinase, and lipase activities. For example,
      isolates grouped in ribotype 55-S-6 had the highest extracellular protease
      activity, while those in ribotypes 50-S-8 and 72-S-3 had the highest
      extracellular lipase activities. We conclude that ribotyping provides a reliable
      method for differentiating Pseudomonas strains with dairy food spoilage
      potential.

PMID- 12513988
TI  - Thermostabilization of bacterial fructosyl-amino acid oxidase by directed
      evolution.
AB  - We succeeded in isolating several thermostable mutant fructosyl-amino acid
      oxidase (FAOX; EC 1.5.3) without reduction of productivity by directed evolution
      that combined an in vivo mutagenesis and membrane assay screening system. Five
      amino acid substitutions (T60A, A188G, M244L, N257S, and L261M) occurred in the
      most thermostable mutant obtained by a fourth round of directed evolution. This
      altered enzyme, FAOX-TE, was stable at 45 degrees C, whereas the wild-type enzyme
      was not stable above 37 degrees C. The K(m) values of FAOX-TE for D-fructosyl-L
      valine and D-fructosyl-glycine were 1.50 and 0.58 mM, respectively, in contrast
      with corresponding values of 1.61 and 0.74 mM for the wild-type enzyme. This
      altered FAOX-TE will be useful in the diagnosis of diabetes.

PMID- 12513989
TI  - Novel approach to the improvement of biphenyl and polychlorinated biphenyl
      degradation activity: promoter implantation by homologous recombination.
AB  - To improve the capabilities of microorganisms relevant for biodegradation, we
      developed a new genetic approach and applied it to the bph operon
      (bphEGF[orf4]A1A2A3CD[orf1]A4R) of Pseudomonas sp. strain KKS102 to enhance its
      biphenyl- and polychlorinated biphenyl (PCB)-degrading activity. A native
      promoter of the bph operon, which was under control, was replaced through
      homologous recombination by a series of promoters that had constitutive activity.
      By testing a series of promoters with various strengths, we were able to obtain
      strains that have enhanced degradation activity for biphenyl and PCBs. This
      strategy removes the rate-limiting factor associated with transcription and has
      the potential to improve the degradation activity of a wide variety of
      microorganisms involved in biodegradation.

PMID- 12513990
TI  - Role of ctc from Listeria monocytogenes in osmotolerance.
AB  - Listeria monocytogenes is a food-borne pathogen with the ability to grow under
      conditions of high osmolarity. In a previous study, we reported the
      identification of 12 proteins showing high induction after salt stress. One of
      these proteins is highly similar to the general stress protein Ctc of Bacillus
      subtilis. In this study, induction of Ctc after salt stress was confirmed at the
      transcriptional level by using RNA slot blot experiments. To explore the role of
      the ctc gene product in resistance to stresses, we constructed a ctc insertional
      mutant. No difference in growth was observed between the wild-type strain LO28
      and the ctc mutant either in rich medium after osmotic or heat stress or in
      minimal medium after heat stress. However, in minimal medium after osmotic
      stress, the growth rate of the mutant was increased by a factor of 2. Moreover,
      electron microscopy analysis showed impaired morphology of the mutant grown under
      osmotic stress conditions in minimal medium. Addition of the osmoprotectant
      glycine betaine to the medium completely abolished the osmotic sensitivity
      phenotype of the ctc mutant. Altogether, these results suggest that the Ctc
      protein of L. monocytogenes is involved in osmotic stress tolerance in the
      absence of any osmoprotectant in the medium.

PMID- 12513991
TI  - Collagenolytic serine-carboxyl proteinase from Alicyclobacillus sendaiensis
      strain NTAP-1: purification, characterization, gene cloning, and heterologous
      expression.
AB  - Enzymatic degradation of collagen produces peptides, the collagen peptides, which
      show a variety of bioactivities of industrial interest. Alicyclobacillus
      sendaiensis strain NTAP-1, a slightly thermophilic, acidophilic bacterium,
      extracellularly produces a novel thermostable collagenolytic activity, which
      exhibits its optimum at the acidic region (pH 3.9) and is potentially applicable
      to the efficient production of such peptides. Here, we describe the purification
      to homogeneity, characterization, gene cloning, and heterologous expression of
      this enzyme, which we call ScpA. Purified ScpA is a monomeric, pepstatin
      insensitive carboxyl proteinase with a molecular mass of 37 kDa which exhibited
      the highest reactivity toward collagen (type I, from a bovine Achilles tendon)
      among the macromolecular substrates examined. On the basis of the sequences of
      the peptides obtained by digestion of collagen with ScpA, the following synthetic
      peptides were designed as substrates for ScpA and kinetically analyzed: Phe-Gly
      Pro-Ala*Gly-Pro-Ile-Gly (k(cat), 5.41 s(-1); K(m), 32 micro M) and Met-Gly-Pro
      Arg*Gly-Phe-Pro-Gly-Ser (k(cat), 351 s(-1); K(m), 214 micro M), where the
      asterisks denote the scissile bonds. The cloned scpA gene encoded a protein of
      553 amino acids with a calculated molecular mass of 57,167 Da. Heterologous
      expression of the scpA gene in the Escherichia coli cells yielded a mature 37-kDa
      species after a two-step proteolytic cleavage of the precursor protein.
      Sequencing of the scpA gene revealed that ScpA was a collagenolytic member of the
      serine-carboxyl proteinase family (the S53 family according to the MEROPS
      database), which is a recently identified proteinase family on the basis of
      crystallography results. Unexpectedly, ScpA was highly similar to a member of
      this family, kumamolysin, whose specificity toward macromolecular substrates has
      not been defined.

PMID- 12513992
TI  - Coevolution of bacteriophage PP01 and Escherichia coli O157:H7 in continuous
      culture.
AB  - The interaction between Escherichia coli O157:H7 and its specific bacteriophage
      PP01 was investigated in chemostat continuous culture. Following the addition of
      bacteriophage PP01, E. coli O157:H7 cell lysis was observed by over 4 orders of
      magnitude at a dilution rate of 0.876 h(-1) and by 3 orders of magnitude at a
      lower dilution rate (0.327 h(-1)). However, the appearance of a series of phage
      resistant E. coli isolates, which showed a low efficiency of plating against
      bacteriophage PP01, led to an increase in the cell concentration in the culture.
      The colony shape, outer membrane protein expression, and lipopolysaccharide
      production of each escape mutant were compared. Cessation of major outer membrane
      protein OmpC production and alteration of lipopolysaccharide composition enabled
      E. coli O157:H7 to escape PP01 infection. One of the escape mutants of E. coli
      O157:H7 which formed a mucoid colony (Mu) on Luria-Bertani agar appeared 56 h
      postincubation at a dilution rate of 0.867 h(-1) and persisted until the end of
      the experiment (approximately 200 h). Mu mutant cells could coexist with
      bacteriophage PP01 in batch culture. Concentrations of the Mu cells and
      bacteriophage PP01 increased together. The appearance of mutant phage, which
      showed a different host range among the O157:H7 escape mutants than wild-type
      PP01, was also detected in the chemostat culture. Thus, coevolution of phage and
      E. coli O157:H7 proceeded as a mutual arms race in chemostat continuous culture.

PMID- 12513993
TI  - Microbial characterization of biofilms in domestic drains and the establishment
      of stable biofilm microcosms.
AB  - We have used heterotrophic plate counts, together with live-dead direct staining
      and denaturing gradient gel electrophoresis (DGGE), to characterize the
      eubacterial communities that had formed as biofilms within domestic sink drain
      outlets. Laboratory microcosms of these environments were established using
      excised biofilms from two separate drain biofilm samples to inoculate constant
      depth film fermentors (CDFFs). Drain biofilms harbored 9.8 to 11.3 log(10) cells
      of viable enteric species and pseudomonads/g, while CDFF-grown biofilms harbored
      10.6 to 11.4 log(10) cells/g. Since live-dead direct staining revealed various
      efficiencies of recovery by culture, samples were analyzed by DGGE, utilizing
      primers specific for the V2-V3 region of eubacterial 16S rDNA. These analyses
      showed that the major PCR amplicons from in situ material were represented in the
      microcosms and maintained there over extended periods. Sequencing of amplicons
      resolved by DGGE revealed that the biofilms were dominated by a small number of
      genera, which were also isolated by culture. One drain sample harbored the
      protozoan Colpoda maupasi, together with rhabtidid nematodes and bdelloid
      rotifers. The microcosm enables the maintenance of stable drain-type bacterial
      communities and represents a useful tool for the modeling of this ecosystem.

PMID- 12513994
TI  - Degradation of anthracene by Mycobacterium sp. strain LB501T proceeds via a novel
      pathway, through o-phthalic acid.
AB  - Mycobacterium sp. strain LB501T utilizes anthracene as a sole carbon and energy
      source. We analyzed cultures of the wild-type strain and of UV-generated mutants
      impaired in anthracene utilization for metabolites to determine the anthracene
      degradation pathway. Identification of metabolites by comparison with authentic
      standards and transient accumulation of o-phthalic acid by the wild-type strain
      during growth on anthracene suggest a pathway through o-phthalic acid and
      protocatechuic acid. As the only productive degradation pathway known so far for
      anthracene proceeds through 2,3-dihydroxynaphthalene and the naphthalene
      degradation pathway to form salicylate, this indicates the existence of a novel
      anthracene catabolic pathway in Mycobacterium sp. LB501T.

PMID- 12513995
TI  - Carbon and hydrogen isotopic fractionation during anaerobic biodegradation of
      benzene.
AB  - Compound-specific isotope analysis has the potential to distinguish physical from
      biological attenuation processes in the subsurface. In this study, carbon and
      hydrogen isotopic fractionation effects during biodegradation of benzene under
      anaerobic conditions with different terminal-electron-accepting processes are
      reported for the first time. Different enrichment factors (epsilon ) for carbon
      (range of -1.9 to -3.6 per thousand ) and hydrogen (range of -29 to -79 per
      thousand ) fractionation were observed during biodegradation of benzene under
      nitrate-reducing, sulfate-reducing, and methanogenic conditions. These
      differences are not related to differences in initial biomass or in rates of
      biodegradation. Carbon isotopic enrichment factors for anaerobic benzene
      biodegradation in this study are comparable to those previously published for
      aerobic benzene biodegradation. In contrast, hydrogen enrichment factors
      determined for anaerobic benzene biodegradation are significantly larger than
      those previously published for benzene biodegradation under aerobic conditions. A
      fundamental difference in the previously proposed initial step of aerobic versus
      proposed anaerobic biodegradation pathways may account for these differences in
      hydrogen isotopic fractionation. Potentially, C-H bond breakage in the initial
      step of the anaerobic benzene biodegradation pathway may account for the large
      fractionation observed compared to that in aerobic benzene biodegradation.
      Despite some differences in reported enrichment factors between cultures with
      different terminal-electron-accepting processes, carbon and hydrogen isotope
      analysis has the potential to provide direct evidence of anaerobic biodegradation
      of benzene in the field.

PMID- 12513996
TI  - Differential growth response of colony-forming alpha- and gamma-proteobacteria in
      dilution culture and nutrient addition experiments from Lake Kinneret (Israel),
      the eastern Mediterranean Sea, and the Gulf of Eilat.
AB  - Even though it is widely accepted that bacterioplankton growth in lakes and
      marine ecosystems is determined by the trophic status of the systems, knowledge
      of the relationship between nutrient concentrations and growth of particular
      bacterial species is almost nonexistent. To address this question, we performed a
      series of culture experiments with water from Lake Kinneret (Israel), the eastern
      Mediterranean Sea, and the Gulf of Eilat (northern Red Sea). In the initial water
      samples, the proportion of CFU was typically <0.002% of the 4',6'-diamidino-2
      phenylindole (DAPI) counts. During incubation until the early stationary phase,
      the proportion of CFU increased to 20% of the DAPI counts and to 2 to 15% of the
      DAPI counts in unenriched lake water and seawater dilution cultures,
      respectively. Sequencing of the 16S ribosomal DNA of colony-forming bacteria in
      these cultures consistently revealed an abundance of alpha-proteobacteria, but
      notable phylogenetic differences were found at the genus level. Marine dilution
      cultures were dominated by bacteria in the Roseobacter clade, while lake dilution
      cultures were dominated by bacteria affiliated with the genera Sphingomonas and
      CAULOBACTER: In nutrient (glucose, ammonium, phosphate) addition experiments the
      CFU comprised 20 to 83% of the newly grown cells. In these incubation experiments
      fast-growing gamma-proteobacteria dominated; in the marine experiments primarily
      different Vibrio and Alteromonas species appeared, while in the lake water
      experiments species of the genera Shewanella, Aeromonas, and Rheinheimera grew.
      These results suggest that major, but different, gamma-proteobacterial genera in
      both freshwater and marine environments have a preference for elevated
      concentrations of nutrients and easily assimilated organic carbon sources but are
      selectively outcompeted by alpha-proteobacteria in the presence of low nutrient
      concentrations.

PMID- 12513997
TI  - L-proline accumulation and freeze tolerance of Saccharomyces cerevisiae are
      caused by a mutation in the PRO1 gene encoding gamma-glutamyl kinase.
AB  - We previously isolated a mutant which showed a high tolerance to freezing that
      correlated with higher levels of intracellular L-proline derived from L-proline
      analogue-resistant mutants. The mutation responsible for the analogue resistance
      and L-proline accumulation was a single nuclear dominant mutation. By introducing
      the mutant-derived genomic library into a non-L-proline-utilizing strain, the
      mutant was found to carry an allele of the wild-type PRO1 gene encoding gamma
      glutamyl kinase, which resulted in a single amino acid replacement; Asp (GAC) at
      position 154 was replaced by Asn (AAC). Interestingly, the allele of PRO1 was
      shown to enhance the activities of gamma-glutamyl kinase and gamma-glutamyl
      phosphate reductase, both of which catalyze the first two steps of L-proline
      synthesis from L-glutamate and which together may form a complex in vivo. When
      cultured in liquid minimal medium, yeast cells expressing the mutated gamma
      glutamyl kinase were found to accumulate intracellular L-proline and showed a
      prominent increase in cell viability after freezing at -20 degrees C compared to
      the viability of cells harboring the wild-type PRO1 gene. These results suggest
      that the altered gamma-glutamyl kinase results in stabilization of the complex or
      has an indirect effect on gamma-glutamyl phosphate reductase activity, which
      leads to an increase in L-proline production in Saccharomyces cerevisiae. The
      approach described in this paper could be a practical method for breeding novel
      freeze-tolerant yeast strains.

PMID- 12513998
TI  - Culture-independent analysis of probiotic products by denaturing gradient gel
      electrophoresis.
AB  - In order to obtain functional and safe probiotic products for human consumption,
      fast and reliable quality control of these products is crucial. Currently,
      analysis of most probiotics is still based on culture-dependent methods involving
      the use of specific isolation media and identification of a limited number of
      isolates, which makes this approach relatively insensitive, laborious, and time
      consuming. In this study, a collection of 10 probiotic products, including four
      dairy products, one fruit drink, and five freeze-dried products, were subjected
      to microbial analysis by using a culture-independent approach, and the results
      were compared with the results of a conventional culture-dependent analysis. The
      culture-independent approach involved extraction of total bacterial DNA directly
      from the product, PCR amplification of the V3 region of the 16S ribosomal DNA,
      and separation of the amplicons on a denaturing gradient gel. Digital capturing
      and processing of denaturing gradient gel electrophoresis (DGGE) band patterns
      allowed direct identification of the amplicons at the species level. This whole
      culture-independent approach can be performed in less than 30 h. Compared with
      culture-dependent analysis, the DGGE approach was found to have a much higher
      sensitivity for detection of microbial strains in probiotic products in a fast,
      reliable, and reproducible manner. Unfortunately, as reported in previous studies
      in which the culture-dependent approach was used, a rather high percentage of
      probiotic products suffered from incorrect labeling and yielded low bacterial
      counts, which may decrease their probiotic potential.

PMID- 12513999
TI  - Purification and characterization of a prolyl aminopeptidase from Debaryomyces
      hansenii.
AB  - A prolyl aminopeptidase (PAP) (EC 3.4.11.5) was isolated from the cell extract of
      Debaryomyces hansenii CECT12487. The enzyme was purified by selective
      fractionation with protamine and ammonium sulfate, followed by two chromatography
      steps, which included gel filtration and anion-exchange chromatography. The PAP
      was purified 248-fold, with a recovery yield of 1.4%. The enzyme was active in a
      broad pH range (from 5 to 9.5), with pH and temperature optima at 7.5 and 45
      degrees C. The molecular mass was estimated to be around 370 kDa. The presence of
      inhibitors of serine and aspartic proteases, bestatin, puromycin, reducing
      agents, chelating agents, and different cations did not have any effect on the
      enzyme activity. Only iodoacetate, p-chloromercuribenzoic acid, and Hg(2+), which
      are inhibitors of cysteine proteases, markedly reduced the enzyme activity. The
      K(m) for proline-7-amido-4-methylcoumarin was 40 micro M. The enzyme exclusively
      hydrolyzed N-terminal-proline-containing substrates. This is the first report on
      the identification and purification of this type of aminopeptidase in yeast,
      which may contribute to the scarce knowledge about D. hansenii proteases and
      their possible roles in meat fermentation.

PMID- 12514000
TI  - Synthesis of GDP-mannose and mannosylglycerate from labeled mannose by
      genetically engineered Escherichia coli without loss of specific isotopic
      enrichment.
AB  - We report the construction of an Escherichia coli mutant that harbors two
      compatible plasmids and that is able to synthesize labeled 2-O-alpha-D-mannosyl-D
      glycerate from externally added labeled mannose without the loss of specific
      isotopic enrichment. The strain carries a deletion in the manA gene, encoding
      phosphomannose isomerase. This deletion prevents the formation of fructose-6
      phosphate from mannose-6-phosphate after the uptake of mannose from the medium by
      mannose-specific enzyme II of the phosphotransferase system (PtsM). The strain
      also has a deletion of the cps gene cluster that prevents the synthesis of
      colanic acid, a mannose-containing polymer. Plasmid-encoded phosphomannomutase
      (cpsG) and mannose-1-phosphate guanylyltransferase (cpsB) ensure the formation of
      GDP-mannose. A second plasmid harbors msg, a gene from Rhodothermus marinus that
      encodes mannosylglycerate synthase, which catalyzes the formation of 2-O-alpha-D
      mannosyl-D-glycerate from GDP-mannose and endogenous glycerate. The rate-limiting
      step in 2-O-alpha-D-mannosyl-D-glycerate formation is the transfer of GDP-mannose
      to glycerate. 2-O-alpha-D-mannosyl-D-glycerate can be released from cells by
      treatment with cold-water shock. The final product is formed in a yield exceeding
      50% the initial quantity of labeled mannose, including loss during preparation
      and paper chromatography.

PMID- 12514001
TI  - Metabolic pathway for propionate utilization by phosphorus-accumulating organisms
      in activated sludge: 13C labeling and in vivo nuclear magnetic resonance.
AB  - In vivo 13C and 31P nuclear magnetic resonance techniques were used to study
      propionate metabolism by activated sludge in enhanced biological phosphorus
      removal systems. The fate of label supplied in [3-13C]propionate was monitored in
      living cells subjected to anaerobic/aerobic cycles. During the anaerobic phase,
      propionate was converted to polyhydroxyalkanoates (PHA) with the following
      monomer composition: hydroxyvalerate, 74.2%; hydroxymethylvalerate, 16.9%;
      hydroxymethylbutyrate, 8.6%; and hydroxybutyrate, 0.3%. The isotopic enrichment
      in the different carbon atoms of hydroxyvalerate (HV) produced during the first
      anaerobic stage was determined: HV5, 59%; HV4, 5.0%; HV3, 1.1%; HV2, 3.5%; and
      HV1, 2.8%. A large proportion of the supplied label ended up on carbon C-5 of HV,
      directly derived from the pool of propionyl-coenzyme A (CoA), which is primarily
      labeled on C-3; useful information on the nature of operating metabolic pathways
      was provided by the extent of labeling on C-1, C-2, and C-4. The labeling pattern
      on C-1 and C-2 was explained by the conversion of propionyl-CoA to acetyl-CoA via
      succinyl-CoA and the left branch of the tricarboxylic acid cycle, which involves
      scrambling of label between the inner carbons of succinate. This constitutes
      solid evidence for the operation of succinate dehydrogenase under anaerobic
      conditions. The labeling in HV4 is explained by backflux from succinate to
      propionyl-CoA. The involvement of glycogen in the metabolism of propionate was
      also demonstrated; moreover, it was shown that the acetyl moiety to the synthesis
      of PHA was derived preferentially from glycogen. According to the proposed
      metabolic scheme, the decarboxylation of pyruvate is coupled to the production of
      hydrogen, and the missing reducing equivalents should be derived from a source
      other than glycogen metabolism.

PMID- 12514002
TI  - Large-scale cultivation of acidophilic hyperthermophiles for recovery of secreted
      proteins.
AB  - An electric water heater was modified for large-scale cultivation of aerobic
      acidophilic hyperthermophiles to enable recovery of secreted proteins. Critical
      changes included thermostat replacement, redesign of the temperature control
      circuit, and removal of the cathodic anticorrosion system. These alterations
      provided accurate temperature and pH control. The bioreactor was used to
      cultivate selected strains of the archaeon Sulfolobus solfataricus and other
      species within this genus. Reformulation of a basal salts medium facilitated
      preparation of large culture volumes and eliminated sterilization-induced
      precipitation of medium components. Substrate induction of synthesis of the S.
      solfataricus-secreted alpha-amylase during growth in a defined medium supported
      the utility of the bioreactor for studies of physiologically regulated processes.
      An improved purification strategy was developed by using strong cation-exchange
      chromatography for recovery of the alpha-amylase and the processing of large
      sample volumes of acidic culture supernatant. These findings should simplify
      efforts to study acidophilic hyperthermophilic microbes and their secreted
      proteins.

PMID- 12514003
TI  - Attachment of Listeria monocytogenes to radish tissue is dependent upon
      temperature and flagellar motility.
AB  - Outbreaks of listeriosis and febrile gastroenteritis have been linked to produce
      contamination by Listeria monocytogenes. In order to begin to understand the
      physiology of the organism in a produce habitat, the ability of L. monocytogenes
      to attach to freshly cut radish tissue was examined. All strains tested had the
      capacity to attach sufficiently well such that they could not be removed during
      washing of the radish slices. A screen was developed to identify Tn917-LTV3
      mutants that were defective in attachment to radish tissue, and three were
      characterized. Two of the three mutations were in genes with unknown functions.
      Both of the unknown genes mapped to a region predicted to contain genes necessary
      for flagellar export; however, only one of the two insertions caused a motility
      defect. The third insertion was found to be in an operon encoding a
      phosphoenolpyruvate-sugar phosphotransferase system. All three mutants were
      defective in attachment when tested at 30 degrees C; the motility mutant had the
      most severe phenotype. However, not all of the mutants were defective when tested
      at other temperatures. These results indicate that L. monocytogenes may use
      different attachment factors at different temperatures and that temperature
      should be considered an important variable in studies of the molecular mechanisms
      of Listeria fitness in complex environments.

PMID- 12514004
TI  - Modifications to United States Environmental Protection Agency methods 1622 and
      1623 for detection of Cryptosporidium oocysts and Giardia cysts in water.
AB  - Collaborative and in-house laboratory trials were conducted to evaluate
      Cryptosporidium oocyst and Giardia cyst recoveries from source and finished-water
      samples by utilizing the Filta-Max system and U.S. Environmental Protection
      Agency (EPA) methods 1622 and 1623. Collaborative trials with the Filta-Max
      system were conducted in accordance with manufacturer protocols for sample
      collection and processing. The mean oocyst recovery from seeded, filtered tap
      water was 48.4% +/- 11.8%, while the mean cyst recovery was 57.1% +/- 10.9%.
      Recovery percentages from raw source water samples ranged from 19.5 to 54.5% for
      oocysts and from 46.7 to 70.0% for cysts. When modifications were made in the
      elution and concentration steps to streamline the Filta-Max procedure, the mean
      percentages of recovery from filtered tap water were 40.2% +/- 16.3% for oocysts
      and 49.4% +/- 12.3% for cysts by the modified procedures, while matrix spike
      oocyst recovery percentages ranged from 2.1 to 36.5% and cyst recovery
      percentages ranged from 22.7 to 68.3%. Blinded matrix spike samples were analyzed
      quarterly as part of voluntary participation in the U.S. EPA protozoan
      performance evaluation program. A total of 15 blind samples were analyzed by
      using the Filta-Max system. The mean oocyst recovery percentages was 50.2% +/-
      13.8%, while the mean cyst recovery percentages was 41.2% +/- 9.9%. As part of
      the quality assurance objectives of methods 1622 and 1623, reagent water samples
      were seeded with a predetermined number of Cryptosporidium oocysts and Giardia
      cysts. Mean recovery percentages of 45.4% +/- 11.1% and 61.3% +/- 3.8% were
      obtained for Cryptosporidium oocysts and Giardia cysts, respectively. These
      studies demonstrated that the Filta-Max system meets the acceptance criteria
      described in U.S. EPA methods 1622 and 1623.

PMID- 12514005
TI  - Degradation of polycyclic aromatic hydrocarbons at low temperature under aerobic
      and nitrate-reducing conditions in enrichment cultures from northern soils.
AB  - The potential for biodegradation of polycyclic aromatic hydrocarbons (PAHs)at low
      temperature and under anaerobic conditions is not well understood, but such
      biodegradation would be very useful for remediation of polluted sites.
      Biodegradation of a mixture of 11 different PAHs with two to five aromatic rings,
      each at a concentration of 10 micro g/ml, was studied in enrichment cultures
      inoculated with samples of four northern soils. Under aerobic conditions, low
      temperature severely limited PAH biodegradation. After 90 days, aerobic cultures
      at 20 degrees C removed 52 to 88% of the PAHs. The most extensive PAH degradation
      under aerobic conditions at 7 degrees C,53% removal, occurred in a culture from
      creosote-contaminated soil. Low temperature did not substantially limit PAH
      biodegradation under nitrate-reducing conditions. Under nitrate-reducing
      conditions,naphthalene, 2-methylnaphthalene, fluorene, and phenanthrene were
      degraded. The most extensive PAH degradation under nitrate-reducing conditions at
      7 degrees C, 39% removal, occurred in a culture from fuel-contaminated Arctic
      soil. In separate transfer cultures from the above Arctic soil, incubated
      anaerobically at 7 degrees C, removal of 2-methylnaphthalene and fluorene was
      stoichiometrically coupled to nitrate removal. Ribosomal intergenic spacer
      analysis suggested that enrichment resulted in a few predominant bacterial
      populations,including members of the genera Acidovorax,Bordetella, Pseudomonas,
      Sphingomonas, and Variovorax. Predominant populations from different soils often
      included phylotypes with nearly identical partial 16S rRNA gene sequences (i.e.,
      same genus) but never included phylotypes with identical ribosomal intergenic
      spacers (i.e., different species or subspecies). The composition of the enriched
      communities appeared to be more affected by presence of oxygen, than by
      temperature or source of the inoculum.

PMID- 12514006
TI  - Elevated abundance of bacteriophage infecting bacteria in soil.
AB  - Here we report the first direct counts of soil bacteriophage and show that
      substantial populations of these viruses exist in soil (grand mean = 1.5 x 10(7)
      g(-1)), at least 350-fold more than the highest numbers estimated from
      traditional viable plaque counts. Adding pure cultures of a Serratia phage to
      soil showed that the direct counting methods with electron microscopy developed
      here underestimated the added phage populations by at least eightfold. So,
      assuming natural phages were similarly underestimated, virus numbers in soil
      averaged 1.5 x 10(8) g(-1), which is equivalent to 4% of the total population of
      bacteria. This high abundance was to some extent confirmed by hybridizing
      colonies grown on Serratia and Pseudomonas selective media with cocktails of
      phage infecting these bacteria. This showed that 8.9 and 3.9%, respectively,
      hybridized with colonies from the two media and confirmed the presence of phage
      DNA sequences in the cultivable fraction of the natural population. Thus, soil
      phage, like their aquatic counterparts, are likely to be important in controlling
      bacterial populations and mediating gene transfer in soil.

PMID- 12514007
TI  - Multicenter validation of the analytical accuracy of Salmonella PCR: towards an
      international standard.
AB  - As part of a major international project for the validation and standardization
      of PCR for detection of five major food-borne pathogens, four primer sets
      specific for Salmonella species were evaluated in-house for their analytical
      accuracy (selectivity and detection limit) in identifying 43 Salmonella spp. and
      47 non-Salmonella strains. The most selective primer set was found to be 139-141
      (K. Rahn, S. A. De Grandis, R. C. Clarke, S. A. McEwen, J. E. Galan, C.
      Ginocchio, R. Curtiss III, and C. L. Gyles, Mol. Cell. Probes 6:271-279, 1992),
      which targets the invA gene. An extended determination of selectivity by using
      364 strains showed that the inclusivity was 99.6% and the exclusivity was 100%
      for the invA primer set. To indicate possible PCR inhibitors derived from the
      sample DNA, an internal amplification control (IAC), which was coamplified with
      the invA target gene, was constructed. In the presence of 300 DNA copies of the
      IAC, the detection probability for primer set 139-141 was found to be 100% when a
      cell suspension containing 10(4) CFU/ml was used as the template in the PCR (50
      CFU per reaction). The primer set was further validated in an international
      collaborative study that included 16 participating laboratories. Analysis with 28
      coded ("blind") DNA samples revealed an analytical accuracy of 98%. Thus, a
      simple PCR assay that is specific for Salmonella spp. and amplifies a chromosomal
      DNA fragment detected by gel electrophoresis was established through extensive
      validation and is proposed as an international standard. This study addresses the
      increasing demand of quality assurance laboratories for standard diagnostic
      methods and presents findings that can facilitate the international comparison
      and exchange of epidemiological data.

PMID- 12514008
TI  - Fluorigenic substrates for the protease activities of botulinum neurotoxins,
      serotypes A, B, and F.
AB  - The seven botulinum neurotoxins (BoNTs) are zinc metalloproteases that cleave
      neuronal proteins involved in neurotransmitter release and are among the most
      toxic natural products known. High-throughput BoNT assays are needed for use in
      antibotulinum drug discovery and to characterize BoNT protease activities.
      Compared to other proteases, BoNTs exhibit unusually stringent substrate
      requirements with respect to amino acid sequences and polypeptide lengths.
      Nonetheless, we have devised a strategy for development of fluorigenic BoNT
      protease assays, based on earlier structure-function studies, that has proven
      successful for three of the seven serotypes: A, B, and F. In synthetic peptide
      substrates, the P(1) and P(3)' residues were substituted with 2,4-dinitrophenyl
      lysine and S-(N-[4-methyl-7-dimethylamino-coumarin-3-yl]-carboxamidomethyl)
      cysteine, respectively. By monitoring the BoNT-catalyzed increase in fluorescence
      over time, initial hydrolysis rates could be obtained in 1 to 2 min when BoNT
      concentrations were 60 ng/ml (about 1 nM) or higher. Each BoNT cleaved its
      fluorigenic substrate at the same location as in the neuronal target protein, and
      kinetic constants indicated that the substrates were selective and efficient. The
      fluorigenic assay for BoNT B was used to characterize a new competitive inhibitor
      of BoNT B protease activity with a K(i) value of 4 micro M. In addition to real
      time activity measurements, toxin concentration determinations, and kinetic
      studies, the BoNT substrates described herein may be directly incorporated into
      automated high-throughput assay systems to screen large numbers of compounds for
      potential antibotulinum drugs.

PMID- 12514009
TI  - Plasmid-encoded diacetyl (acetoin) reductase in Leuconostoc pseudomesenteroides.
AB  - A plasmid-borne diacetyl (acetoin) reductase (butA) from Leuconostoc
      pseudomesenteroides CHCC2114 was sequenced and cloned. Nucleotide sequence
      analysis revealed an open reading frame encoding a protein of 257 amino acids
      which had high identity at the amino acid level to diacetyl (acetoin) reductases
      reported previously. Downstream of the butA gene of L. pseudomesenteroides, but
      coding in the opposite orientation, a putative DNA recombinase was identified. A
      two-step PCR approach was used to construct FPR02, a butA mutant of the wild-type
      strain, CHCC2114. FPR02 had significantly reduced diacetyl (acetoin) reductase
      activity with NADH as coenzyme, but not with NADPH as coenzyme, suggesting the
      presence of another diacetyl (acetoin)-reducing activity in L.
      pseudomesenteroides. Plasmid-curing experiments demonstrated that the butA gene
      is carried on a 20-kb plasmid in L. pseudomesenteroides.

PMID- 12514010
TI  - Effect of raw-milk cheese consumption on the enterococcal flora of human feces.
AB  - Enterococci are one of the major facultative anaerobic bacterial groups that
      reside in the human gastrointestinal tract. In the present study, the composition
      of the enterococcal fecal flora in three healthy humans was analyzed before,
      during, and after the daily consumption of approximately 125 g of a raw-milk
      Cheddar-type cheese containing 3.2 x 10(4) enterococci/g of cheese. Enterococcal
      counts ranged between 1.4 x 10(2) and 2.5 x 10(8) CFU/g of feces and differed
      from subject to subject and from week to week. The cheese contained mainly
      Enterococcus casseliflavus and a small population of Enterococcus faecalis.
      Clonal relationships were determined by pulsed-field gel electrophoresis. Before
      and after consumption of the cheese, samples from humans contained mainly
      Enterococcus faecium, with some of the clones being resident. During consumption
      of the cheese, one particular transient clone of E. faecalis, clone Fs2, which
      was present in small numbers in the cheese, largely dominated the feces. Two
      clones of E. casseliflavus from the cheese were also found in the feces of one of
      the subjects during cheese consumption. These results suggest that a clone need
      not be present in a food in high numbers to establish itself in the intestine.

PMID- 12514011
TI  - Evaluation of PCR amplification bias by terminal restriction fragment length
      polymorphism analysis of small-subunit rRNA and mcrA genes by using defined
      template mixtures of methanogenic pure cultures and soil DNA extracts.
AB  - Terminal restriction fragment length polymorphism (T-RFLP) analysis is a widely
      used method for profiling microbial community structure in different habitats by
      targeting small-subunit (SSU) rRNA and also functional marker genes. It is not
      known, however, whether relative gene frequencies of individual community members
      are adequately represented in post-PCR amplicon frequencies as shown by T-RFLP.
      In this study, precisely defined artificial template mixtures containing genomic
      DNA of four different methanogens in various ratios were prepared for subsequent
      T-RFLP analysis. PCR amplicons were generated from defined mixtures targeting not
      only the SSU rRNA but also the methyl-coenzyme M reductase (mcrA/mrtA) genes of
      methanogens. Relative amplicon frequencies of microorganisms were quantified by
      comparing fluorescence intensities of characteristic terminal restriction
      fragments. SSU ribosomal DNA (rDNA) template ratios in defined template mixtures
      of the four-membered community were recovered absolutely by PCR-T-RFLP analysis,
      which demonstrates that the T-RFLP analysis evaluated can give a quantitative
      view of the template pool. SSU rDNA-targeted T-RFLP analysis of a natural
      community was found to be highly reproducible, independent of PCR annealing
      temperature, and unaffected by increasing PCR cycle numbers. Ratios of mcrA
      targeted T-RFLP analysis were biased, most likely by PCR selection due to the
      degeneracy of the primers used. Consequently, for microbial community analyses,
      each primer system used should be evaluated carefully for possible PCR bias. In
      fact, such bias can be detected by using T-RFLP analysis as a tool for the
      precise quantification of the PCR product pool.

PMID- 12514012
TI  - Molecular identification of ectomycorrhizal mycelium in soil horizons.
AB  - Molecular identification techniques based on total DNA extraction provide a
      unique tool for identification of mycelium in soil. Using molecular
      identification techniques, the ectomycorrhizal (EM) fungal community under
      coniferous vegetation was analyzed. Soil samples were taken at different depths
      from four horizons of a podzol profile. A basidiomycete-specific primer pair
      (ITS1F-ITS4B) was used to amplify fungal internal transcribed spacer (ITS)
      sequences from total DNA extracts of the soil horizons. Amplified basidiomycete
      DNA was cloned and sequenced, and a selection of the obtained clones was analyzed
      phylogenetically. Based on sequence similarity, the fungal clone sequences were
      sorted into 25 different fungal groups, or operational taxonomic units (OTUs).
      Out of 25 basidiomycete OTUs, 7 OTUs showed high nucleotide homology (> or = 99%)
      with known EM fungal sequences and 16 were found exclusively in the mineral soil.
      The taxonomic positions of six OTUs remained unclear. OTU sequences were compared
      to sequences from morphotyped EM root tips collected from the same sites. Of the
      25 OTUs, 10 OTUs had > or = 98% sequence similarity with these EM root tip
      sequences. The present study demonstrates the use of molecular techniques to
      identify EM hyphae in various soil types. This approach differs from the
      conventional method of EM root tip identification and provides a novel approach
      to examine EM fungal communities in soil.

PMID- 12514013
TI  - mRNA differential display in a microbial enrichment culture: simultaneous
      identification of three cyclohexanone monooxygenases from three species.
AB  - mRNA differential display has been used to identify cyclohexanone oxidation genes
      in a mixed microbial community derived from a wastewater bioreactor. Thirteen DNA
      fragments randomly amplified from the total RNA of an enrichment subculture
      exposed to cyclohexanone corresponded to genes predicted to be involved in the
      degradation of cyclohexanone. Nine of these DNA fragments are part of genes
      encoding three distinct Baeyer-Villiger cyclohexanone monooxygenases from three
      different bacterial species present in the enrichment culture. In Arthrobacter
      sp. strain BP2 and Rhodococcus sp. strain Phi2, the monooxygenase is part of a
      gene cluster that includes all the genes required for the degradation of
      cyclohexanone, while in Rhodococcus sp. strain Phi1 the genes surrounding the
      monooxygenase are not predicted to be involved in this degradation pathway but
      rather seem to belong to a biosynthetic pathway. Furthermore, in the case of
      Arthrobacter strain BP2, three other genes flanking the monooxygenase were
      identified by differential display, demonstrating that the repeated sampling of
      bacterial operons shown earlier for a pure culture (D. M. Walters, R. Russ, H.
      Knackmuss, and P. E. Rouviere, Gene 273:305-315, 2001) is also possible for
      microbial communities. The activity of the three cyclohexanone monooxygenases was
      confirmed and characterized following their expression in Escherichia coli.

PMID- 12514014
TI  - Mitogen-activated protein kinase in Pfiesteria piscicida and its growth rate
      related expression.
AB  - A full-length cDNA (1,434 bp) of mitogen-activated protein kinase (MAPK), a key
      molecule of a signal transduction cascade, was isolated from the estuarine
      heterotrophic dinoflagellate Pfiesteria piscicida. This cDNA (Ppmapk1) encoded a
      protein (PpMAPK1) of 428 amino acid residues that shared about 30 to 40% amino
      acid similarity with MAPKs in other organisms. Phylogenetic analysis indicated
      that PpMAPK1 was tightly clustered with MAPK3 in protozoans. Using reverse
      transcription-PCR, expression of this gene was evaluated for P. piscicida
      cultures grown under different conditions. While salinity shock, heat shock,
      starvation, and a subsequent encounter with prey did not appear to affect
      expression of this gene, Ppmapk1 expression level was correlated with growth
      rate, suggesting involvement of this gene in the regulation of cell proliferation
      in the organism.

PMID- 12514015
TI  - Capsid functions of inactivated human picornaviruses and feline calicivirus.
AB  - The exceptional stability of enteric viruses probably resides in their capsids.
      The capsid functions of inactivated human picornaviruses and feline calicivirus
      (FCV) were determined. Viruses were inactivated by UV, hypochlorite, high
      temperature (72 degrees C), and physiological temperature (37 degrees C), all of
      which are pertinent to transmission via food and water. Poliovirus (PV) and
      hepatitis A virus (HAV) are transmissible via water and food, and FCV is the best
      available surrogate for the Norwalk-like viruses, which are leading causes of
      food-borne and waterborne disease in the United States. The capsids of all 37
      degrees C-inactivated viruses still protected the viral RNA against RNase, even
      in the presence of proteinase K, which contrasted with findings with viruses
      inactivated at 72 degrees C. The loss of ability of the virus to attach to
      homologous cell receptors was universal, regardless of virus type and
      inactivation method, except for UV-inactivated HAV, and so virus inactivation was
      almost always accompanied by the loss of virus attachment. Inactivated HAV and
      FCV were captured by homologous antibodies. However, inactivated PV type 1 (PV-1)
      was not captured by homologous antibody and 37 degrees C-inactivated PV-1 was
      only partially captured. The epitopes on the capsids of HAV and FCV are evidently
      discrete from the receptor attachment sites, unlike those of PV-1. These findings
      indicate that the primary target of UV, hypochlorite, and 72 degrees C
      inactivation is the capsid and that the target of thermal inactivation (37
      degrees C versus 72 degrees C) is temperature dependent.

PMID- 12514016
TI  - Secretion of active-form Streptoverticillium mobaraense transglutaminase by
      Corynebacterium glutamicum: processing of the pro-transglutaminase by a
      cosecreted subtilisin-Like protease from Streptomyces albogriseolus.
AB  - The transglutaminase secreted by Streptoverticillium mobaraense is a useful
      enzyme in the food industry. A fragment of transglutaminase was secreted by
      Corynebacterium glutamicum when it was coupled on a plasmid to the promoter and
      signal peptide of a cell surface protein from C. glutamicum. We analyzed the
      signal peptide and the pro-domain of the transglutaminase gene and found that the
      signal peptide consists of 31 amino acid residues and the pro-domain consists of
      45 residues. When the pro-domain of the transglutaminase was used, the pro
      transglutaminase was secreted efficiently by C. glutamicum but had no enzymatic
      activity. However, when the plasmid carrying the S. mobaraense transglutaminase
      also encoded SAM-P45, a subtilisin-like serine protease derived from Streptomyces
      albogriseolus, the peptide bond to the C side of 41-Ser of the pro
      transglutaminase was hydrolyzed, and the pro-transglutaminase was converted to an
      active form. Our findings suggest that C. glutamicum has potential as a host for
      industrial-scale protein production.

PMID- 12514017
TI  - A labeling study to elucidate the biosynthesis of 4-(4-hydroxyphenyl)-butan-2-one
      (raspberry ketone) by Nidula niveo-tomentosa.
AB  - Submerged cells of the basidiomycete Nidula niveo-tomentosa, a microbial producer
      of 4-(4-hydroxyphenyl)-butan-2-one, were supplemented with (13)C-labeled L
      phenylalanines and with [1-(13)C]glucose. Labeled transformation products were
      detected by a novel method of analyzing stable isotope-labeled metabolites, gas
      chromatography (GC) coupled to an atomic emission detector, and by GC-mass
      spectrometry. A benzoate moiety was side chain elongated according to the poly
      beta-keto scheme. The presence of an acetyl coenzyme A-carboxylase inhibitor
      shifted the spectrum of products to benzyl compounds. Hence, the fungal pathway
      differs from the one established for plant tissues.

PMID- 12514018
TI  - Enhanced heterologous expression of two Streptomyces griseolus cytochrome P450s
      and Streptomyces coelicolor ferredoxin reductase as potentially efficient
      hydroxylation catalysts.
AB  - The herbicide-inducible, soluble cytochrome P450s CYP105A1 and CYP105B1 and their
      adjacent ferredoxins, Fd1 and Fd2, of Streptomyces griseolus were expressed in
      Escherichia coli to high levels. Conditions for high-level expression of active
      enzyme able to catalyze hydroxylation have been developed. Analysis of the
      expression levels of the P450 proteins in several different E. coli expression
      hosts identified E. coli BL21 Star(DE3)pLysS as the optimal host cell to express
      CYP105B1 as judged by CO difference spectra. Examination of the codons used in
      the CYP1051A1 sequence indicated that it contains a number of codons
      corresponding to rare E. coli tRNA species. The level of its expression was
      improved in the modified forms of E. coli BL21(DE3), which contain extra copies
      of rare codon E. coli tRNA genes. The activity of correctly folded cytochrome
      P450s was further enhanced by cloning a ferredoxin reductase from Streptomyces
      coelicolor downstream of CYP105A1 and CYP105B1 and their adjacent ferredoxins.
      Expression of CYP105A1 and CYP105B1 was also achieved in Streptomyces lividans
      1326 by cloning the P450 genes and their ferredoxins into the expression vector
      pBW160. S. lividans 1326 cells containing CYP105A1 or CYP105B1 were able
      efficiently to dealkylate 7-ethoxycoumarin.

PMID- 12514019
TI  - Purification and genetic characterization of plantaricin NC8, a novel coculture
      inducible two-peptide bacteriocin from Lactobacillus plantarum NC8.
AB  - A new, coculture-inducible two-peptide bacteriocin named plantaricin NC8 (PLNC8)
      was isolated from Lactobacillus plantarum NC8 cultures which had been induced
      with Lactococcus lactis MG1363 or Pediococcus pentosaceus FBB63. This bacteriocin
      consists of two distinct peptides, named alpha and beta, which were separated by
      C(2)-C(18) reverse-phase chromatography and whose complementary action is
      necessary for full plantaricin NC8 activity. N-terminal sequencing of both
      purified peptides showed 28 and 34 amino acids residues for PLNC8 alpha and PLNC8
      beta, respectively, which showed no sequence similarity to other known
      bacteriocins. Mass spectrometry analysis showed molecular masses of 3,587 Da
      (alpha) and 4,000 Da (beta). The corresponding genes, designated plNC8A and
      plNC8B, were sequenced, and their nucleotide sequences revealed that both
      peptides are produced as bacteriocin precursors of 47 and 55 amino acids,
      respectively, which include N-terminal leader sequences of the double-glycine
      type. The mature alpha and beta peptides contain 29 and 34 amino acids,
      respectively. An open reading frame, orfC, which encodes a putative immunity
      protein was found downstream of plNC8B and overlapping plNC8A. Upstream of the
      putative -35 region of plNC8B, two direct repeats of 9 bp were identified, which
      agrees with the consensus sequence and structure of promoters of class II
      bacteriocin operons whose expression is dependent on an autoinduction mechanism.

PMID- 12514020
TI  - Morphological and phylogenetic characterizations of freshwater Thioploca species
      from Lake Biwa, Japan, and Lake Constance, Germany.
AB  - Filamentous, gliding, sulfide-oxidizing bacteria of the genus Thioploca were
      found on sediments in profundal areas of Lake Biwa, a Japanese freshwater
      mesotrophic lake, and were characterized morphologically and phylogenetically.
      The Lake Biwa Thioploca resembled morphologically Thioploca ingrica, a brackish
      water species from a Danish fjord. The diameters of individual trichomes were 3
      to 5.6 microm; the diameters of complete Thioploca filaments ranged from 18 to 75
      micro m. The cell lengths ranged from 1.2 to 3.8 micro m. In transmission
      electron microscope specimens stained with uranyl acetate, dense intracellular
      particles were found, which did not show any positive signals for phosphorus and
      sulfur in an X-ray analysis. The 16S rRNA gene of the Thioploca from Lake Biwa
      was amplified by using newly designed Thioploca-specific primers (706-Thioploca,
      Biwa160F, and Biwa829R) in combination with general bacterial primers in order to
      avoid nonspecific amplification of contaminating bacterial DNA. Denaturing
      gradient gel electrophoresis (DGGE) analysis of the three overlapping PCR
      products resulted in single DGGE bands, indicating that a single 16S rRNA gene
      had been amplified. With the same method, the Thioploca from Lake Constance was
      examined. The 16S rRNA sequence was verified by performing fluorescence in situ
      hybridization targeted at specific motifs of the Lake Biwa THIOPLOCA: Positive
      signals were obtained with the bacterial probe EUB-338, the gamma-proteobacterial
      probe GAM42a, and probe Biwa829 targeting the Lake Biwa THIOPLOCA: Based on the
      nearly complete 16S rRNA sequence and on morphological similarities, the
      Thioploca from Lake Biwa and the Thioploca from Lake Constance are closely
      related to T. ingrica and to each other.

PMID- 12514021
TI  - Production of optically pure D-lactic acid in mineral salts medium by
      metabolically engineered Escherichia coli W3110.
AB  - The resistance of polylactide to biodegradation and the physical properties of
      this polymer can be controlled by adjusting the ratio of L-lactic acid to D
      lactic acid. Although the largest demand is for the L enantiomer, substantial
      amounts of both enantiomers are required for bioplastics. We constructed
      derivatives of Escherichia coli W3110 (prototrophic) as new biocatalysts for the
      production of D-lactic acid. These strains (SZ40, SZ58, and SZ63) require only
      mineral salts as nutrients and lack all plasmids and antibiotic resistance genes
      used during construction. D-Lactic acid production by these new strains
      approached the theoretical maximum yield of two molecules per glucose molecule.
      The chemical purity of this D-lactic acid was approximately 98% with respect to
      soluble organic compounds. The optical purity exceeded 99%. Competing pathways
      were eliminated by chromosomal inactivation of genes encoding fumarate reductase
      (frdABCD), alcohol/aldehyde dehydrogenase (adhE), and pyruvate formate lyase
      (pflB). The cell yield and lactate productivity were increased by a further
      mutation in the acetate kinase gene (ackA). Similar improvements could be
      achieved by addition of 10 mM acetate or by an initial period of aeration. All
      three approaches reduced the time required to complete the fermentation of 5%
      glucose. The use of mineral salts medium, the lack of antibiotic resistance genes
      or plasmids, the high yield of D-lactate, and the high product purity should
      reduce costs associated with nutrients, purification, containment, biological
      oxygen demand, and waste treatment.

PMID- 12514022
TI  - Potential rates of fermentation in digesta from the gastrointestinal tract of
      pigs: effect of feeding fermented liquid feed.
AB  - Microbial catabolic capacity in digesta from the gastrointestinal tract of pigs
      fed either dry feed or fermented liquid feed (FLF) was determined with the
      PhenePlate multisubstrate system. The in vitro technique was modified to analyze
      the kinetics of substrate catabolism mediated by the standing stock of enzymes
      (potential rates of fermentation), allowing a quantitative evaluation of the
      dietary effect on the catabolic capacity of the microbiota. In total, the
      potential rates of fermentation were significantly reduced in digesta from the
      large intestine (cecum, P < 0.1; colon, P < 0.01; and rectum, P < 0.0001) of pigs
      fed FLF compared to pigs fed dry feed. No effect of diet was observed in the
      stomach (P = 0.71) or the distal part of the small intestine (P = 0.97). The
      highest rates of fermentation and the most significant effect of diet were
      observed for readily fermentable carbohydrates like maltose, sucrose, and
      lactose. Feeding FLF to pigs also led to a reduction in the large intestine of
      the total counts of anaerobic bacteria in general and lactic acid bacteria
      specifically, as well as of microbial activity, as determined by the
      concentration of ATP and short-chain fatty acids. The low-molecular-weight
      carbohydrates were fermented mainly to lactic acid in the FLF before being fed to
      the animals. This may have limited microbial nutrient availability in the digesta
      reaching the large intestine of pigs fed FLF and may have caused the observed
      reduction in activity and density of the cecal and colonic microbial population.
      On the other hand, feeding FLF to pigs reduced the viable counts of coliform
      bacteria (indicator of Escherichia coli and Salmonella spp.) most profoundly in
      the stomach and the distal part of the small intestine, probably due to the
      bactericidal effect of lactic acid and low pH. The results presented clearly
      demonstrate that feeding FLF to pigs had a great impact on the indigenous
      microbiota, as reflected in bacterial numbers, short-chain fatty acid
      concentration, and substrate utilization. However, completely different
      mechanisms may be involved in the proximal and the distal parts of the
      gastrointestinal tract. The present study illustrates the utility of the
      PhenePlate system for quantifying the catabolic capacity of the indigenous
      gastrointestinal tract microbiota.

PMID- 12514023
TI  - Substrate specificity and enantioselectivity of 4-hydroxyacetophenone
      monooxygenase.
AB  - The 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB
      catalyzes NADPH- and oxygen-dependent Baeyer-Villiger oxidation of 4
      hydroxyacetophenone to the corresponding acetate ester. Using the purified enzyme
      from recombinant Escherichia coli, we found that a broad range of carbonylic
      compounds that are structurally more or less similar to 4-hydroxyacetophenone are
      also substrates for this flavin-containing monooxygenase. On the other hand,
      several carbonyl compounds that are substrates for other Baeyer-Villiger
      monooxygenases (BVMOs) are not converted by HAPMO. In addition to performing
      Baeyer-Villiger reactions with aromatic ketones and aldehydes, the enzyme was
      also able to catalyze sulfoxidation reactions by using aromatic sulfides.
      Furthermore, several heterocyclic and aliphatic carbonyl compounds were also
      readily converted by this BVMO. To probe the enantioselectivity of HAPMO, the
      conversion of bicyclohept-2-en-6-one and two aryl alkyl sulfides was studied. The
      monooxygenase preferably converted (1R,5S)-bicyclohept-2-en-6-one, with an
      enantiomeric ratio (E) of 20, thus enabling kinetic resolution to obtain the
      (1S,5R) enantiomer. Complete conversion of both enantiomers resulted in the
      accumulation of two regioisomeric lactones with moderate enantiomeric excess (ee)
      for the two lactones obtained [77% ee for (1S,5R)-2 and 34% ee for (1R,5S)-3].
      Using methyl 4-tolyl sulfide and methylphenyl sulfide, we found that HAPMO is
      efficient and highly selective in the asymmetric formation of the corresponding
      (S)-sulfoxides (ee > 99%). The biocatalytic properties of HAPMO described here
      show the potential of this enzyme for biotechnological applications.

PMID- 12514024
TI  - 2-Hydroxypenta-2,4-dienoate metabolic pathway genes in a strong polychlorinated
      biphenyl degrader, Rhodococcus sp. strain RHA1.
AB  - A gram-positive polychlorinated biphenyl (PCB) degrader, Rhodococcus sp. strain
      RHA1, metabolizes biphenyl through the 2-hydroxypenta-2,4-dienoate (HPD) and
      benzoate metabolic pathways. The HPD metabolic pathway genes, the HPD hydratase
      (bphE1), 4-hydroxy-2-oxovalerate aldolase (bphF1), and acetaldehyde dehydrogenase
      (acylating) (bphG) genes, were cloned from RHA1. The deduced amino acid sequences
      of bphGF1E1 have 30 to 58% identity with those of the HPD metabolic pathway genes
      of gram-negative bacteria. The order of these genes, bphG-bphF1-bphE1, differs
      from that of the HPD metabolic pathway genes, bphE-bphG-bphF, in gram-negative
      degraders of PCB, phenol, and toluene. Reverse transcription-PCR experiments
      indicated that the bphGF1E1 genes are inducibly cotranscribed in cells grown on
      biphenyl and ethylbenzene. Primer extension analysis revealed that the
      transcriptional initiation site exists within the bphR gene located adjacent to
      and upstream of bphG, which is deduced to code a transcriptional regulator. The
      respective enzyme activities of bphGF1E1 gene products were detected in
      Rhodococcus erythropolis IAM1399 carrying a bphGF1E1 plasmid. The insertional
      inactivation of the bphE1, bphF1, and bphG genes resulted in the loss of the
      corresponding enzyme activities and diminished growth on both biphenyl and
      ethylbenzene. Severe growth interference was observed during growth on biphenyl.
      The growth defects were partially restored by the introduction of plasmids
      containing the respective intact genes. These results indicated that the cloned
      bphGF1E1 genes are not only responsible for the primary metabolism of HPD during
      growth on both biphenyl and ethylbenzene but are also involved in preventing the
      accumulation of unexpected toxic metabolites, which interfere with the growth of
      RHA1.

PMID- 12514025
TI  - Biodegradation of an alicyclic hydrocarbon by a sulfate-reducing enrichment from
      a gas condensate-contaminated aquifer.
AB  - We used ethylcyclopentane (ECP) as a model alicyclic hydrocarbon and investigated
      its metabolism by a sulfate-reducing bacterial enrichment obtained from a gas
      condensate-contaminated aquifer. The enrichment coupled the consumption of ECP
      with the stoichiometrically expected amount of sulfate reduced. During ECP
      biodegradation, we observed the transient accumulation of metabolite peaks by gas
      chromatography-mass spectrometry, three of which had identical mass spectrometry
      profiles. Mass-spectral similarities to analogous authentic standards allowed us
      to identify these metabolites as ethylcyclopentylsuccinic acids,
      ethylcyclopentylpropionic acid, ethylcyclopentylcarboxylic acid, and
      ethylsuccinic acid. Based on these findings, we propose a pathway for the
      degradation of this alicyclic hydrocarbon. Furthermore, a putative metabolite
      similar to ethylcyclopentylsuccinic acid was also found in samples of
      contaminated groundwater from the aquifer. However, no such finding was evident
      for samples collected from wells located upgradient of the gas condensate spill.
      Microbial community analysis of the ECP-degrading enrichment by denaturing
      gradient gel electrophoresis revealed the presence of at least three different
      organisms using universal eubacterial primers targeting 550 bp of the 16S rRNA
      gene. Based on sequence analysis, these organisms are phylogenetically related to
      the genera Syntrophobacter and Desulfotomaculum as well as a member of the
      Cytophaga-Flexibacter-Bacteroides group. The evidence suggests that alicyclic
      hydrocarbons such as ECP can be anaerobically activated by the addition to the
      double bond of fumarate to form alkylsuccinate derivatives under sulfate-reducing
      conditions and that the reaction occurs in the laboratory and in hydrocarbon
      impacted environments.

PMID- 12514026
TI  - Phylogenetic diversity of lactic acid bacteria associated with paddy rice silage
      as determined by 16S ribosomal DNA analysis.
AB  - A total of 161 low-G+C-content gram-positive bacteria isolated from whole-crop
      paddy rice silage were classified and subjected to phenotypic and genetic
      analyses. Based on morphological and biochemical characters, these presumptive
      lactic acid bacterium (LAB) isolates were divided into 10 groups that included
      members of the genera Enterococcus, Lactobacillus, Lactococcus, Leuconostoc,
      Pediococcus, and WEISSELLA: Analysis of the 16S ribosomal DNA (rDNA) was used to
      confirm the presence of the predominant groups indicated by phenotypic analysis
      and to determine the phylogenetic affiliation of representative strains. The
      virtually complete 16S rRNA gene was PCR amplified and sequenced. The sequences
      from the various LAB isolates showed high degrees of similarity to those of the
      GenBank reference strains (between 98.7 and 99.8%). Phylogenetic trees based on
      the 16S rDNA sequence displayed high consistency, with nodes supported by high
      bootstrap values. With the exception of one species, the genetic data was in
      agreement with the phenotypic identification. The prevalent LAB, predominantly
      homofermentative (66%), consisted of Lactobacillus plantarum (24%), Lactococcus
      lactis (22%), Leuconostoc pseudomesenteroides (20%), Pediococcus acidilactici
      (11%), Lactobacillus brevis (11%), Enterococcus faecalis (7%), Weissella kimchii
      (3%), and Pediococcus pentosaceus (2%). The present study, the first to fully
      document rice-associated LAB, showed a very diverse community of LAB with a
      relatively high number of species involved in the fermentation process of paddy
      rice silage. The comprehensive 16S rDNA-based approach to describing LAB
      community structure was valuable in revealing the large diversity of bacteria
      inhabiting paddy rice silage and enabling the future design of appropriate
      inoculants aimed at improving its fermentation quality.

PMID- 12514027
TI  - Compost-induced suppression of Pythium damping-off is mediated by fatty-acid
      metabolizing seed-colonizing microbial communities.
AB  - Leaf composts were studied for their suppressive effects on Pythium ultimum
      sporangium germination, cottonseed colonization, and the severity of Pythium
      damping-off of cotton. A focus of the work was to assess the role of fatty-acid
      metabolizing microbial communities in disease suppression. Suppressiveness was
      expressed within the first few hours of seed germination as revealed by reduced
      P. ultimum sporangium germination, reduced seed colonization, and reduced damping
      off in transplant experiments. These reductions were not observed when
      cottonseeds were sown in a conducive leaf compost. Microbial consortia recovered
      from the surface of cottonseeds during the first few hours of germination in
      suppressive compost (suppressive consortia) induced significant levels of damping
      off suppression, whereas no suppression was induced by microbial consortia
      recovered from cottonseeds germinated in conducive compost (conducive consortia).
      Suppressive consortia rapidly metabolized linoleic acid, whereas conducive
      consortia did not. Furthermore, populations of fatty-acid-metabolizing bacteria
      and actinobacteria were higher in suppressive consortia than in conducive
      consortia. Individual bacterial isolates varied in their ability to metabolize
      linoleic acid and protect seedlings from damping-off. Results indicate that
      communities of compost-inhabiting microorganisms colonizing cottonseeds within
      the first few hours after sowing in a Pythium-suppressive compost play a major
      role in the suppression of P. ultimum sporangium germination, seed colonization,
      and damping-off. Results further indicate that fatty acid metabolism by these
      seed-colonizing bacterial consortia can explain the Pythium suppression observed.

PMID- 12514028
TI  - In situ exposure to low herbicide concentrations affects microbial population
      composition and catabolic gene frequency in an aerobic shallow aquifer.
AB  - The aim of this study was to evaluate how the in situ exposure of a Danish
      subsurface aquifer to phenoxy acid herbicides at low concentrations (<40 micro g
      l(-1)) changes the microbial community composition. Sediment and groundwater
      samples were collected inside and outside the herbicide-exposed area and were
      analyzed for the presence of general microbial populations, Pseudomonas bacteria,
      and specific phenoxy acid degraders. Both culture-dependent and culture
      independent methods were applied. The abundance of microbial phenoxy acid
      degraders (10(0) to 10(4) g(-1) sediment) was determined by most probable number
      assays, and their presence was only detected in herbicide-exposed sediments.
      Similarly, PCR analysis showed that the 2,4-dichlorophenoxyacetic acid
      degradation pathway genes tfdA and tfdB (10(2) to 10(3) gene copies g(-1)
      sediment) were only detected in sediments from contaminated areas of the aquifer.
      PCR-restriction fragment length polymorphism measurements demonstrated the
      presence of different populations of tfd genes, suggesting that the in situ
      herbicide degradation was caused by the activity of a heterogeneous population of
      phenoxy acid degraders. The number of Pseudomonas bacteria measured by either PCR
      or plating on selective agar media was higher in sediments subjected to high
      levels of phenoxy acid. Furthermore, high numbers of CFU compared to direct
      counting of 4',6-diamidino-2-phenylindole-stained cells in the microscope
      suggested an increased culturability of the indigenous microbial communities from
      acclimated sediments. The findings of this study demonstrate that continuous
      exposure to low herbicide concentrations can markedly change the bacterial
      community composition of a subsurface aquifer.

PMID- 12514029
TI  - Online monitoring of Escherichia coli ghost production.
AB  - Controlled expression of cloned phi X174 gene E in gram-negative bacteria results
      in lysis of the bacteria by the formation of a transmembrane tunnel structure
      built through the cell envelope complex. Production of bacterial ghosts is
      routinely monitored by classical microbiological procedures. These include
      determination of the turbidity of the culture and the total number of cells and
      the number of reproductive cells present during the time course of growth and
      lysis. Although conceptually simple, these methods are labor intensive and time
      consuming, providing a complete set of results after the determination of viable
      cell counts. To avoid culturing methods for bacterial growth, an alternative flow
      cytometric procedure is presented for the quantification of ghosts and polarized,
      as well as depolarized, nonlysed cells within a culture. For this method, which
      is based on the discriminatory power of the membrane potential-sensitive dye bis
      (1,3-dibutylbarbituric acid) trimethine oxonol, a staining protocol was developed
      and optimized for the maximum discrepancy in fluorescence between bacterial
      ghosts and viable cells. The total quantitative analysis procedure takes less
      than 2 min. The results derived from classical or cytometric analyses correlate
      with respect to the total cell numbers and the viability of the culture.

PMID- 12514030
TI  - Monitoring the bacterial population dynamics in sourdough fermentation processes
      by using PCR-denaturing gradient gel electrophoresis.
AB  - Four sourdoughs (A to D) were produced under practical conditions by using a
      starter mixture of three commercially available sourdough starters and a baker's
      yeast constitutively containing various species of lactic acid bacteria (LAB).
      The sourdoughs were continuously propagated until the composition of the LAB
      flora remained stable. Two LAB-specific PCR-denaturing gradient gel
      electrophoresis (DGGE) systems were established and used to monitor the
      development of the microflora. Depending on the prevailing ecological conditions
      in the different sourdough fermentations, only a few Lactobacillus species were
      found to be competitive and became dominant. In sourdough A (traditional process
      with rye flour), Lactobacillus sanfranciscensis and a new species, L. mindensis,
      were detected. In rye flour sourdoughs B and C, which differed in the process
      temperature, exclusively L. crispatus and L. pontis became the predominant
      species in sourdough B and L. crispatus, L. panis, and L. frumenti became the
      predominant species in sourdough C. On the other hand, in sourdough D
      (corresponding to sourdough C but produced with rye bran), L. johnsonii and L.
      reuteri were found. The results of PCR-DGGE were consistent with those obtained
      by culturing, except for sourdough B, in which L. fermentum was also detected.
      Isolates of the species L. sanfranciscensis and L. fermentum were shown by
      randomly amplified polymorphic DNA-PCR analysis to originate from the commercial
      starters and the baker's yeast, respectively.

PMID- 12514031
TI  - Changes in microbial community composition and function during a polyaromatic
      hydrocarbon phytoremediation field trial.
AB  - The purpose of this study was to investigate the mechanism by which
      phytoremediation systems promote hydrocarbon degradation in soil. The composition
      and degradation capacity of the bulk soil microbial community during the
      phytoremediation of soil contaminated with aged hydrocarbons was assessed. In the
      bulk soil, the level of catabolic genes involved in hydrocarbon degradation
      (ndoB, alkB, and xylE) as well as the mineralization of hexadecane and
      phenanthrene was higher in planted treatment cells than in treatment cells with
      no plants. There was no detectable shift in the 16S ribosomal DNA (rDNA)
      composition of the bulk soil community between treatments, but there were plant
      specific and -selective effects on specific catabolic gene prevalence. Tall
      Fescue (Festuca arundinacea) increased the prevalence of ndoB, alkB, and xylE as
      well as naphthalene mineralization in rhizosphere soil compared to that in bulk
      soil. In contrast, Rose Clover (Trifolium hirtum) decreased catabolic gene
      prevalence and naphthalene mineralization in rhizosphere soil. The results
      demonstrated that phytoremediation systems increase the catabolic potential of
      rhizosphere soil by altering the functional composition of the microbial
      community. This change in composition was not detectable by 16S rDNA but was
      linked to specific functional genotypes with relevance to petroleum hydrocarbon
      degradation.

PMID- 12514032
TI  - Enhanced toxic metal accumulation in engineered bacterial cells expressing
      Arabidopsis thaliana phytochelatin synthase.
AB  - Phytochelatins (PCs) are metal-binding cysteine-rich peptides, enzymatically
      synthesized in plants and yeasts from glutathione in response to heavy metal
      stress by PC synthase (EC 2.3.2.15). In an attempt to increase the ability of
      bacterial cells to accumulate heavy metals, the Arabidopsis thaliana gene
      encoding PC synthase (AtPCS) was expressed in Escherichia coli. A marked
      accumulation of PCs was observed in vivo together with a decrease in the
      glutathione cellular content. When bacterial cells expressing AtPCS were placed
      in the presence of heavy metals such as cadmium or the metalloid arsenic,
      cellular metal contents were increased 20- and 50-fold, respectively. We discuss
      the possibility of using genes of the PC biosynthetic pathway to design bacterial
      strains or higher plants with increased abilities to accumulate toxic metals, and
      also arsenic, for use in bioremediation and/or phytoremediation processes.

PMID- 12514033
TI  - Optimal growth and ethanol production from xylose by recombinant Saccharomyces
      cerevisiae require moderate D-xylulokinase activity.
AB  - D-Xylulokinase (XK) is essential for the metabolism of D-xylose in yeasts.
      However, overexpression of genes for XK, such as the Pichia stipitis XYL3 gene
      and the Saccharomyces cerevisiae XKS gene, can inhibit growth of S. cerevisiae on
      xylose. We varied the copy number and promoter strength of XYL3 or XKS1 to see
      how XK activity can affect xylose metabolism in S. cerevisiae. The S. cerevisiae
      genetic background included single integrated copies of P. stipitis XYL1 and XYL2
      driven by the S. cerevisiae TDH1 promoter. Multicopy and single-copy constructs
      with either XYL3 or XKS1, likewise under control of the TDH1 promoter, or with
      the native P. stipitis promoter were introduced into the recombinant S.
      cerevisiae. In vitro enzymatic activity of XK increased with copy number and
      promoter strength. Overexpression of XYL3 and XKS1 inhibited growth on xylose but
      did not affect growth on glucose even though XK activities were three times
      higher in glucose-grown cells. Growth inhibition increased and ethanol yields
      from xylose decreased with increasing XK activity. Uncontrolled XK expression in
      recombinant S. cerevisiae is inhibitory in a manner analogous to the substrate
      accelerated cell death observed with an S. cerevisiae tps1 mutant during glucose
      metabolism. To bypass this effect, we transformed cells with a tunable expression
      vector containing XYL3 under the control of its native promoter into the FPL
      YS1020 strain and screened the transformants for growth on, and ethanol
      production from, xylose. The selected transformant had approximately four copies
      of XYL3 per haploid genome and had moderate XK activity. It converted xylose into
      ethanol efficiently.

PMID- 12514034
TI  - Gene Cloning, purification, and characterization of a phosphodiesterase from
      Delftia acidovorans.
AB  - A novel phosphodiesterase (PdeA) was purified from Delftia acidovorans, the gene
      encoding the enzyme was cloned and expressed in Escherichia coli, and the
      recombinant enzyme was purified to apparent homogeneity and characterized. PdeA
      is an 85-kDa trimer that exhibits maximal activity at 65 degrees C and pH 10 even
      though it was isolated from a mesophilic bacterium. Although PdeA exhibited both
      mono- and diesterase activity, it was most active on the phosphodiester bis(p
      nitrophenyl)phosphate with a K(m) of 2.9 +/- 0.1 mM and a k(cat) of 879 +/- 73
      min(-1). The enzyme showed sequence similarity to cyclic AMP (cAMP)
      phosphodiesterase and cyclic nucleotide phosphodiesterases and exhibited activity
      on cAMP in vivo when the gene was expressed in E. coli. The IS1071 transposon
      insertion sequence was found downstream of pdeA.

PMID- 12514035
TI  - Genetic variability within Borrelia burgdorferi sensu lato genospecies
      established by PCR-single-strand conformation polymorphism analysis of the rrfA
      rrlB intergenic spacer in ixodes ricinus ticks from the Czech Republic.
AB  - In Europe the Borrelia burgdorferi sensu lato complex is represented by five
      distinct genospecies: Borrelia burgdorferi sensu stricto, Borrelia afzelii,
      Borrelia garinii, Borrelia valaisiana, and Borrelia lusitaniae. These taxonomic
      entities are known to differ in their specific associations with vertebrate hosts
      and to provoke distinct clinical manifestations in human patients. However,
      exceptions to these rules have often been observed, indicating that strains
      belonging to a single genospecies may be more heterogeneous than expected. It is,
      therefore, important to develop alternative identification tools which are able
      to distinguish Borrelia strains not only at the specific level but also at the
      intraspecific level. DNA from a sample of 370 Ixodes ricinus ticks collected in
      the Czech Republic was analyzed by PCR for the presence of a approximately 230-bp
      fragment of the rrfA-rrlB intergenic spacer of Borrelia spp. A total of 20.5% of
      the ticks were found to be positive. The infecting genospecies were identified by
      analyzing the amplified products by the restriction fragment length polymorphism
      (RFLP) method with restriction enzyme MseI and by single-strand conformation
      polymorphism (SSCP) analysis. The two methods were compared, and PCR-SSCP
      analysis appeared to be a valuable tool for rapid identification of spirochetes
      at the intraspecific level, particularly when large samples are examined.
      Furthermore, by using PCR-SSCP analysis we identified a previously unknown
      Borrelia genotype, genotype I-77, which would have gone unnoticed if RFLP
      analysis alone had been used.

PMID- 12514036
TI  - Gene replacement in mycobacteria by using incompatible plasmids.
AB  - A simple and efficient delivery system was developed for making targeted gene
      knockouts in Mycobacterium smegmatis. This delivery system relies on the use of a
      pair of replicating plasmids, which are incompatible. Incompatible plasmids share
      elements of the same replication machinery and so compete with each other during
      both replication and partitioning into daughter cells. Such plasmids can be
      maintained together in the presence of antibiotics; however, removal of selection
      leads to the loss of one or both plasmids. For mutagenesis, two replicating
      plasmids based on pAL5000 are introduced; one of these plasmids carries a mutated
      allele of the targeted gene. Homologous recombination is allowed to take place,
      and either one or both of the vectors are lost through the pressure of
      incompatibility, allowing the phenotypic effects of the mutant to be studied.
      Several different plasmid combinations were tested to optimize loss in the
      absence of antibiotic selection. pAL5000 carries two replication genes (repA and
      repB), which act in trans, and the use of vectors that each lack one rep gene and
      complement each other resulted in the loss of both plasmids in M. smegmatis and
      Mycobacterium bovis BCG. The rate of loss was increased by the incorporation of
      an additional incompatibility region in one of the plasmids. To facilitate
      cloning when the system was used, we constructed plasmid vector pairs that allow
      simple addition of selection and screening genes on flexible gene cassettes.
      Using this system, we demonstrated that M. smegmatis pyrF mutants could be
      isolated at high frequency. This method should also be useful in other species in
      which pAL5000 replicates, including Mycobacterium tuberculosis.

PMID- 12514037
TI  - Genes for chlorogenate and hydroxycinnamate catabolism (hca) are linked to
      functionally related genes in the dca-pca-qui-pob-hca chromosomal cluster of
      Acinetobacter sp. strain ADP1.
AB  - Hydroxycinnamates are ubiquitous in the environment because of their
      contributions to the structure and defense mechanisms of plants. Additional plant
      products, many of which are formed in response to stress, support the growth of
      Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca
      qui-pob chromosomal cluster. In an appropriate genetic background, it was
      possible to select for an Acinetobacter strain that had lost the ability to grow
      with caffeate, a commonly occurring hydroxycinnamate. The newly identified
      mutation was shown to be a deletion in a gene designated hcaC and encoding a
      ligase required for conversion of commonly occurring hydroxycinnamates (caffeate,
      ferulate, coumarate, and 3,4-dihydroxyphenylpropionate) to thioesters. Linkage
      analysis showed that hcaC is linked to pobA. Downstream from hcaC and transcribed
      in the direction opposite the direction of pobA transcription are open reading
      frames designated hcaDEFG. Functions of these genes were inferred from sequence
      comparisons and from the properties of knockout mutants. HcaD corresponded to an
      acyl coenzyme A (acyl-CoA) dehydrogenase required for conversion of 3,4
      dihydroxyphenylpropionyl-CoA to caffeoyl-CoA. HcaE appears to encode a member of
      a family of outer membrane proteins known as porins. Knockout mutations in hcaF
      confer no discernible phenotype. Knockout mutations in hcaG indicate that this
      gene encodes a membrane-associated esterase that hydrolyzes chlorogenate to
      quinate, which is metabolized in the periplasm, and caffeate, which is
      metabolized by intracellular enzymes. The chromosomal location of hcaG, between
      hcaC (required for growth with caffeate) and quiA (required for growth with
      quinate), provided the essential clue that led to the genetic test of HcaG as the
      esterase that produces caffeate and quinate from chlorogenate. Thus, in this
      study, organization within what is now established as the dca-pca-qui-pob-hca
      chromosomal cluster provided essential information about the function of genes in
      the environment.

PMID- 12514038
TI  - Molecular characterization of Legionella populations present within slow sand
      filters used for fungal plant pathogen suppression in horticultural crops.
AB  - The total bacterial community of an experimental slow sand filter (SSF) was
      analyzed by denaturing gradient gel electrophoresis (DGGE) of partial 16S rRNA
      gene PCR products. One dominant band had sequence homology to Legionella species,
      indicating that these bacteria were a large component of the SSF bacterial
      community. Populations within experimental and commercial SSF units were studied
      by using Legionella-specific PCR primers, and products were studied by DGGE and
      quantitative PCR analyses. In the experimental SSF unit, the DGGE profiles for
      sand column, reservoir, storage tank, and headwater tank samples each contained
      at least one intense band, indicating that a single Legionella strain was
      predominant in each sample. Greater numbers of DGGE bands of equal intensity were
      detected in the outflow water sample. Sequence analysis of these PCR products
      showed that several Legionella species were present and that the organisms
      exhibited similarity to strains isolated from environmental and clinical samples.
      Quantitative PCR analysis of the SSF samples showed that from the headwater
      sample through the sand column, the number of Legionella cells decreased,
      resulting in a lower number of cells in the outflow water. In the commercial SSF,
      legionellae were also detected in the sand column samples. Storing prefilter
      water or locating SSF units within greenhouses, which are often maintained at
      temperatures that are higher than the ambient temperature, increases the risk of
      growth of Legionella and should be avoided. Care should also be taken when used
      filter sand is handled or replaced, and regular monitoring of outflow water would
      be useful, especially if the water is used for misting or overhead irrigation.

PMID- 12514039
TI  - Diversity, frequency, and persistence of Escherichia coli O157 strains from range
      cattle environments.
AB  - Genetic diversity, isolation frequency, and persistence were determined for
      Escherichia coli O157 strains from range cattle production environments. Over the
      11-month study, analysis of 9,122 cattle fecal samples, 4,083 water source
      samples, and 521 wildlife fecal samples resulted in 263 isolates from 107 samples
      presumptively considered E. coli O157 as determined by culture and latex
      agglutination. Most isolates (90.1%) were confirmed to be E. coli O157 by PCR
      detection of intimin and Shiga toxin genes. Pulsed-field gel electrophoresis
      (PFGE) of XbaI-digested preparations revealed 79 unique patterns (XbaI-PFGE
      subtypes) from 235 typeable isolates confirmed to be E. coli O157. By analyzing
      up to three isolates per positive sample, we detected an average of 1.80 XbaI
      PFGE subtypes per sample. Most XbaI-PFGE subtypes (54 subtypes) were identified
      only once, yet the seven most frequently isolated subtypes represented over one
      half of the E. coli O157 isolates (124 of 235 isolates). Recurring XbaI-PFGE
      subtypes were recovered from samples on up to 10 sampling occasions and up to 10
      months apart. Seven XbaI-PFGE subtypes were isolated from both cattle feces and
      water sources, and one of these also was isolated from the feces of a wild
      opossum (Didelphis sp.). The number of XbaI-PFGE subtypes, the variable frequency
      and persistence of subtypes, and the presence of identical subtypes in cattle
      feces, free-flowing water sources, and wildlife feces indicate that the complex
      molecular epidemiology of E. coli O157 previously described for confined cattle
      operations is also evident in extensively managed range cattle environments.

PMID- 12514040
TI  - Growth dynamics of Salmonella enterica strains on alfalfa sprouts and in waste
      seed irrigation water.
AB  - Alfalfa sprouts and other seed sprouts have been implicated in numerous outbreaks
      of salmonellosis. The source of these epidemics appears to have been low-level
      contamination of seeds by Salmonella bacteria that developed into clinically
      significant populations during the seed germination process. To test the
      possibility that Salmonella enterica strains carry host range determinants that
      allow them to grow on alfalfa, strains isolated from alfalfa or other sources
      were surveyed for their ability to grow on germinating alfalfa seeds. An S.
      enterica serovar Cubana strain originally isolated from contaminated alfalfa
      sprouts multiplied most rapidly during the initial 24 h of the seed germination
      process. Germinating alfalfa seeds supported the multiplication of S. enterica
      cells prior to the emergence of the root radicle at 72 h. Thereafter, much lower
      rates of multiplication were apparent. The ability of S. enterica to grow on
      germinating alfalfa seeds was independent of the serovar, isolation source, or
      virulence of the strain. Isolates obtained from alfalfa attained population
      levels similar to those observed for strains isolated from contaminated meat
      products or stools. Each of the strains could be detected in the waste irrigation
      water, with populations being strongly correlated with those detected on the
      germinating alfalfa seeds. The S. enterica strains were capable of utilizing the
      waste irrigation water as a sole carbon and nitrogen source. S. enterica strains
      thus appear to grow saprophytically on soluble organics released from seeds
      during early phases of germination. The ability to detect S. enterica in the
      waste irrigation water early in the germination process indicates that this
      method may be used as a simple way to monitor the contamination of sprouts during
      commercial operations.

PMID- 12514041
TI  - Longitudinal study of Escherichia coli O157 in a cattle finishing unit.
AB  - In a longitudinal study in a Finnish cattle finishing unit we investigated
      excretion and sources of Escherichia coli O157 in bulls from postweaning until
      slaughter. Three groups of 31 to 42 calves were sampled in a calf transporter
      before they entered the farm and four to seven times at approximately monthly
      intervals at the farm. All calves sampled in the livestock transporter were
      negative for E. coli O157 on arrival, whereas positive animals were detected 1
      day later. During the fattening period the E. coli O157 infection rate varied
      between 0 and 38.5%. The animals were also found to be shedding during the cold
      months. E. coli O157 was isolated from samples taken from water cups, floors, and
      feed passages. E. coli O157 was detected in 9.7 to 38.9% of the fecal samples
      taken at slaughter, while only two rumen samples and one carcass surface sample
      were found to be positive. E. coli O157 was isolated from barn surface samples
      more often when the enrichment time was 6 h than when the enrichment time was 24
      h (P < 0.0001). Fecal samples taken at the abattoir had lower counts (< or = 0.4
      MPN/g) than fecal samples at the farm (P < 0.05). E. coli O157 was isolated more
      often from 10-g fecal samples than from 1-g fecal samples (P < 0.0001). Most farm
      isolates belonged to one pulsed-field gel electrophoresis (PFGE) genotype
      (79.6%), and the rest belonged to closely related PFGE genotypes. In conclusion,
      this study indicated that the finishing unit rather than introduction of new
      cattle was the source of E. coli O157 at the farm and that E. coli O157 seemed to
      persist well on barn surfaces.

PMID- 12514042
TI  - Acetic acid increases stability of silage under aerobic conditions.
AB  - The effects of various compounds on the aerobic stability of silages were
      evaluated. It has been observed that inoculation of whole-crop maize with
      homofermentative lactic acid bacteria leads to silages which have low stability
      against aerobic deterioration, while inoculation with heterofermentative lactic
      acid bacteria, such as Lactobacillus brevis or Lactobacillus buchneri, increases
      stability. Acetic acid has been proven to be the sole substance responsible for
      the increased aerobic stability, and this acid acts as an inhibitor of spoilage
      organisms. Therefore, stability increases exponentially with acetic acid
      concentration. Only butyric acid has a similar effect. Other compounds, like
      lactic acid, 1,2-propanediol, and 1-propanol, have been shown to have no effect,
      while fructose and mannitol reduce stability.

PMID- 12514043
TI  - 2-n-Pentyl-4-quinolinol produced by a marine Alteromonas sp. and its potential
      ecological and biogeochemical roles.
AB  - Bacterium-bacterium interactions occur at intimate spatial scales on the order of
      micrometers, but our knowledge of interactions at this level is rudimentary.
      Antagonism is a potential interaction in such microenvironments. To study the
      ecological role of antibiosis, we developed a model system involving an
      antibiotic-producing isolate (SWAT5) derived from a marine particle and its
      dominant antibiotic product, 2-n-pentyl-4-quinolinol (PQ). This system was used
      to address questions about the significance of this antibiotic for microbial
      ecology and carbon cycling on particles. We characterized the chemical and
      inhibitory properties of PQ in relation to the mechanisms used by particle
      associated bacteria in interacting with particles and with other attached
      bacteria. PQ was produced by SWAT5 only on surfaces. When SWAT5 was grown in
      polysaccharide matrices, PQ diffused within the matrices but not into the
      surrounding seawater. SWAT5 might thus be able to generate a localized zone of
      high antibiotic concentration on particles suspended or sinking through seawater.
      Target bacterial respiration was most sensitive to PQ (75 nM), while inhibition
      of DNA synthesis, protein synthesis, and bacterial motility required higher
      (micromolar) PQ levels. The presence of PQ altered the composition of the
      bacterial community that colonized and developed in a model particle system. PQ
      also inhibited Synechococcus and phytoplankton growth. Our results suggest that
      antibiosis may significantly influence community composition and activities of
      attached bacterial and thus regulate the biogeochemical fate of particulate
      organic matter in the ocean.

PMID- 12514044
TI  - Inactivation of feline calicivirus and adenovirus type 40 by UV radiation.
AB  - Little information regarding the effectiveness of UV radiation on the
      inactivation of caliciviruses and enteric adenoviruses is available. Analysis of
      human calicivirus resistance to disinfectants is hampered by the lack of animal
      or cell culture methods that can determine the viruses' infectivity. The
      inactivation kinetics of enteric adenovirus type 40 (AD40), coliphage MS-2, and
      feline calicivirus (FCV), closely related to the human caliciviruses based on
      nucleic acid organization and capsid architecture, were determined after exposure
      to low-pressure UV radiation in buffered demand-free (BDF) water at room
      temperature. In addition, UV disinfection experiments were also carried out in
      treated groundwater with FCV and AD40. AD40 was more resistant than either FCV or
      coliphage MS-2 in both BDF water and groundwater. The doses of UV required to
      achieve 99% inactivation of AD40, coliphage MS-2, and FCV in BDF water were 109,
      55, and 16 mJ/cm(2), respectively. The doses of UV required to achieve 99%
      inactivation of AD40, coliphage MS-2, and FCV in groundwater were slightly lower
      than those in BDF water. FCV was inactivated by 99% by 13 mJ/cm(2) in treated
      groundwater. A dose of 103 mJ/cm(2) was required for 99% inactivation of AD40 in
      treated groundwater. The results of this study indicate that if FCV is an
      adequate surrogate for human caliciviruses, then their inactivation by UV
      radiation is similar to those of other single-stranded RNA enteric viruses, such
      as poliovirus. In addition, AD40 appears to be more resistant to UV disinfection
      than previously reported.

PMID- 12514045
TI  - Influences of pond geochemistry, temperature, and freeze-thaw on terminal
      anaerobic processes occurring in sediments of six ponds of the McMurdo Ice Shelf,
      near Bratina Island, Antarctica.
AB  - The effects of freeze-thaw, freezing and sediment geochemistry on terminal
      anaerobic processes occurring in sediments taken from below cyanobacterial mats
      in meltwater ponds of the McMurdo Ice Shelf in Antarctica were investigated.
      Depending on the geochemical and physical status of the sediments (i.e., frozen
      or thawed), as well as passage of sediment through a freeze-thaw cycle, terminal
      carbon and electron flow shifted in which the proportions of hydrogen and acetate
      utilized for methanogenesis and sulfate reduction changed. Thus, in low-sulfate
      (or chloride) sediment which was thawed and incubated at 4 degrees C, total
      carbon and electron flow were mediated by acetate-driven sulfate reduction and
      H(2)-driven methanogenesis. When the same sediments were incubated frozen, both
      methanogenesis and sulfate reduction decreased. However, under these conditions
      methanogenesis was favored over sulfate reduction, and carbon flow from acetate
      to methane increased relative to sulfate reduction; >70% of methane was
      contributed by acetate, and more than 80% of acetate was oxidized by pathways not
      coupled to sulfate reduction. In high-sulfate pond sediments, sulfate reduction
      was a major process mediating terminal carbon and electron flow in both unfrozen
      and frozen incubations. However, as with low-sulfate sediments, acetate oxidation
      became uncoupled from sulfate reduction with freezing. Geochemical and
      temperature effects could be expressed by linear models in which the log
      (methanogenesis to sulfate reduction) was negative log linear with respect to
      either temperature or the log of the sulfate (or chloride) concentration. From
      these relationships it was possible to predict the ratio for a given temperature
      (low-sulfate sediments) or sulfate (chloride) concentration. Small transitory
      changes, such as elevated sulfate reduction coupled to increased acetate
      turnover, resulted from application of a freeze-thaw cycle to low-salinity pond
      sediments. The results demonstrate how ecophysiological processes may change in
      anaerobic systems under extreme conditions (e.g., freezing) and provide new
      insights into microbial events occurring under these conditions.

PMID- 12514046
TI  - A field investigation of Bacillus anthracis contamination of U.S. Department of
      Agriculture and other Washington, D.C., buildings during the anthrax attack of
      October 2001.
AB  - In response to a bioterrorism attack in the Washington, D.C., area in October
      2001, a mobile laboratory (ML) was set up in the city to conduct rapid molecular
      tests on environmental samples for the presence of Bacillus anthracis spores and
      to route samples for further culture analysis. The ML contained class I laminar
      flow hoods, a portable autoclave, two portable real-time PCR devices (Ruggedized
      Advanced Pathogen Identification Device [RAPID]), and miscellaneous supplies and
      equipment to process samples. Envelopes and swab and air samples collected from
      30 locations in the metropolitan area once every three days were subjected to
      visual examination and DNA extraction, followed by real-time PCR using freeze
      dried, fluorescent-probe-based reagents. Surface swabs and air samples were also
      cultured for B. anthracis at the National Veterinary Service Laboratory (NVSL) in
      Ames, Iowa. From 24 October 2001 to 15 September 2002, 2,092 pieces of mail were
      examined, 405 real-time PCR assays were performed (comprising 4,639 samples), and
      at the NVSL 6,275 samples were subjected to over 18,000 platings. None of the PCR
      assays on DNA extracted from swab and air samples were positive, but viable
      spores were cultured from surface swabs taken from six locations in the
      metropolitan area in October, November, and December 2001 and February, March,
      and May 2002. DNA extracted from these suspected B. anthracis colonies was
      positive by real-time and conventional PCRs for the lethal factor, pXO1, and for
      capA and vrr genes; sequence analysis of the latter amplicons indicated >99%
      homology with the Ames, vollum, B6273-93, C93022281, and W-21 strains of B.
      anthracis, suggesting they arose from cross-contamination during the attack
      through the mail. The RAPID-based PCR analysis provided fast confirmation of
      suspect colonies from an overnight incubation on agar plates.

PMID- 12514047
TI  - Survival and growth of Francisella tularensis in Acanthamoeba castellanii.
AB  - Francisella tularensis is a highly infectious, facultative intracellular
      bacterium which causes epidemics of tularemia in both humans and mammals at
      regular intervals. The natural reservoir of the bacterium is largely unknown,
      although it has been speculated that protozoa may harbor it. To test this
      hypothesis, Acanthamoeba castellanii was cocultured with a strain of F.
      tularensis engineered to produce green fluorescent protein (GFP) in a nutrient
      rich medium. GFP fluorescence within A. castellanii was then monitored by flow
      cytometry and fluorescence microscopy. In addition, extracellular bacteria were
      distinguished from intracellular bacteria by targeting with monoclonal
      antibodies. Electron microscopy was used to determine the intracellular location
      of F. tularensis in A. castellanii, and viable counts were obtained for both
      extracellular and intracellular bacteria. The results showed that many F.
      tularensis cells were located intracellularly in A. castellanii cells. The
      bacteria multiplied within intracellular vacuoles and eventually killed many of
      the host cells. F. tularensis was found in intact trophozoites, excreted
      vesicles, and cysts. Furthermore, F. tularensis grew faster in cocultures with A.
      castellanii than it did when grown alone in the same medium. This increase in
      growth was accompanied by a decrease in the number of A. castellanii cells. The
      interaction between F. tularensis and amoebae demonstrated in this study
      indicates that ubiquitous protozoa might be an important environmental reservoir
      for F. tularensis.

PMID- 12514048
TI  - Bacteria associated with cysts of the soybean cyst nematode (Heterodera
      glycines).
AB  - The soybean cyst nematode (SCN), Heterodera glycines, causes economically
      significant damage to soybeans (Glycine max) in many parts of the world. The
      cysts of this nematode can remain quiescent in soils for many years as a
      reservoir of infection for future crops. To investigate bacterial communities
      associated with SCN cysts, cysts were obtained from eight SCN-infested farms in
      southern Ontario, Canada, and analyzed by culture-dependent and -independent
      means. Confocal laser scanning microscopy observations of cyst contents revealed
      a microbial flora located on the cyst exterior, within a polymer plug region and
      within the cyst. Microscopic counts using 5-(4,6-dichlorotriazine-2
      yl)aminofluorescein staining and in situ hybridization (EUB 338) indicated that
      the cysts contained (2.6 +/- 0.5) x 10(5) bacteria (mean +/- standard deviation)
      with various cellular morphologies. Filamentous fungi were also observed. Live
      dead staining indicated that the majority of cyst bacteria were viable. The probe
      Nile red also bound to the interior polymer, indicating that it is lipid rich in
      nature. Bacterial community profiles determined by denaturing gradient gel
      electrophoresis analysis were simple in composition. Bands shared by all eight
      samples included the actinobacterium genera Actinomadura and STREPTOMYCES: A
      collection of 290 bacteria were obtained by plating macerated surface-sterilized
      cysts onto nutrient broth yeast extract agar or on actinomycete medium. These
      were clustered into groups of siblings by repetitive extragenic palindromic PCR
      fingerprinting, and representative isolates were tentatively identified on the
      basis of 16S rRNA gene sequence. Thirty phylotypes were detected, with the
      collection dominated by Lysobacter and Variovorax spp. This study has revealed
      the cysts of this important plant pathogen to be rich in a variety of bacteria,
      some of which could presumably play a role in the ecology of SCN or have
      potential as biocontrol agents.

PMID- 12514049
TI  - Genetic diversity of isolates of Glomus mosseae from different geographic areas
      detected by vegetative compatibility testing and biochemical and molecular
      analysis.
AB  - We detected, for the first time, the occurrence of vegetative incompatibility
      between different isolates of the arbuscular mycorrhizal fungal species Glomus
      mosseae. Vegetative compatibility tests performed on germlings belonging to the
      same isolate showed that six geographically different isolates were capable of
      self-anastomosing, and that the percentage of hyphal contacts leading to fusions
      ranged from 60 to 85%. Successful anastomoses were characterized by complete
      fusion of hyphal walls, protoplasm continuity and occurrence of nuclei in the
      middle of hyphal bridges. No anastomoses could be detected between hyphae
      belonging to different isolates, which intersected without any reaction in 49 to
      68% of contacts. Microscopic examinations detected hyphal incompatibility
      responses in diverse pairings, consisting of protoplasm retraction from the tips
      and septum formation in the approaching hyphae, even before physical contact with
      neighboring hyphae. Interestingly, many hyphal tips showed precontact tropism,
      suggesting that specific recognition signals may be involved during this stage.
      The intraspecific genetic diversity of G. mosseae revealed by vegetative
      compatibility tests was confirmed by total protein profiles and internal
      transcribed spacer-restriction fragment length polymorphism profiles, which
      evidenced a higher level of molecular diversity between the two European isolates
      IMA1 and BEG25 than between IMA1 and the two American isolates. Since arbuscular
      mycorrhizal fungi lack a tractable genetic system, vegetative compatibility tests
      may represent an easy assay for the detection of genetically different mycelia
      and an additional powerful tool for investigating the population structure and
      genetics of these obligate symbionts.

PMID- 12514050
TI  - Phylogenetic position and in situ identification of ectosymbiotic spirochetes on
      protists in the termite gut.
AB  - Phylogenetic relationships, diversity, and in situ identification of spirochetes
      in the gut of the termite Neotermes koshunensis were examined without
      cultivation, with an emphasis on ectosymbionts attached to flagellated protists.
      Spirochetes in the gut microbial community investigated so far are related to the
      genus Treponema and divided into two phylogenetic clusters. In situ
      hybridizations with a 16S rRNA-targeting consensus oligonucleotide probe for one
      cluster (known as termite Treponema cluster I) detected both the ectosymbiotic
      spirochetes on gut protists and the free-swimming spirochetes in the gut fluid of
      N. koshunensis. The probe for the other cluster (cluster II), which has been
      identified as ectosymbionts on gut protists of two other termite species,
      Reticulitermes speratus and Hodotermopsis sjoestedti, failed to detect any
      spirochete population. The absence of cluster II spirochetes in N. koshunensis
      was confirmed by intensive 16S ribosomal DNA (rDNA) clone analysis, in which
      remarkably diverse spirochetes of 45 phylotypes were identified, almost all
      belonging to cluster I. Ectosymbiotic spirochetes of the three gut protist
      species Devescovina sp., Stephanonympha sp., and Oxymonas sp. in N. koshunensis
      were identified by their 16S rDNA and by in situ hybridizations using specific
      probes. The probes specific for these ectosymbionts did not receive a signal from
      the free-swimming spirochetes. The ectosymbionts were dispersed in cluster I of
      the phylogeny, and they formed distinct phylogenetic lineages, suggesting
      multiple origins of the spirochete attachment. Each single protist cell harbored
      multiple spirochete species, and some of the spirochetes were common among
      protist species. The results indicate complex relationships of the ectosymbiotic
      spirochetes with the gut protists.

PMID- 12514051
TI  - Antifungal activity of phenyllactic acid against molds isolated from bakery
      products.
AB  - Phenyllactic acid (PLA) has recently been found in cultures of Lactobacillus
      plantarum that show antifungal activity in sourdough breads. The fungicidal
      activity of PLA and growth inhibition by PLA were evaluated by using a
      microdilution test and 23 fungal strains belonging to 14 species of Aspergillus,
      Penicillium, and Fusarium that were isolated from bakery products, flours, or
      cereals. Less than 7.5 mg of PLA ml(-1) was required to obtain 90% growth
      inhibition for all strains, while fungicidal activity against 19 strains was
      shown by PLA at levels of < or = 10 mg ml(-1). Levels of growth inhibition of 50
      to 92.4% were observed for all fungal strains after incubation for 3 days in the
      presence of 7.5 mg of PLA ml(-1) in buffered medium at pH 4, which is a condition
      more similar to those in real food systems. Under these experimental conditions
      PLA caused an unpredictable delaying effect that was more than 2 days long for 12
      strains, including some mycotoxigenic strains of Penicillium verrucosum and
      Penicillium citrinum and a strain of Penicillium roqueforti (the most widespread
      contaminant of bakery products); a growth delay of about 2 days was observed for
      seven other strains. The effect of pH on the inhibitory activity of PLA and the
      combined effects of the major organic acids produced by lactic acid bacteria
      isolated from sourdough bread (PLA, lactic acid, and acetic acid) were also
      investigated. The ability of PLA to act as a fungicide and delay the growth of a
      variety of fungal contaminants provides new perspectives for possibly using this
      natural antimicrobial compound to control fungal contaminants and extend the
      shelf lives of foods and/or feedstuffs.

PMID- 12514052
TI  - Evaluation of the redox dye 5-cyano-2,3-tolyl-tetrazolium chloride for activity
      studies by simultaneous use of microautoradiography and fluorescence in situ
      hybridization.
AB  - Three microscopic in situ techniques were used simultaneously to investigate
      viability and activity on a single-cell level in activated sludge. The redox dye
      5-cyano-2,3-tolyl-tetrazolium chloride (CTC) was compared with
      microautoradiography (MAR) and fluorescence in situ hybridization (FISH) to
      indicate activity of cells in Thiothrix filaments and in single floc-forming
      bacteria. The signals from MAR and FISH correlated well, whereas only 65% of the
      active Thiothrix cells and 41% of all single cells were detectable by CTC
      reduction, which mainly targeted the most active cells.

PMID- 12514053
TI  - Distribution of microorganisms in the subsurface of the manus basin hydrothermal
      vent field in Papua New Guinea.
AB  - The distribution of microorganisms in the subsurfaces of hydrothermal vents was
      investigated by using subvent rock core samples. Microbial cells and ATP were
      detected from cores taken at depths of less than 99.4 and 44.8 m below the
      seafloor (mbsf), respectively. Cores from various depths were incubated
      anaerobically with a heterotrophic medium. Growth at 60 and 90 degrees C was
      ascribed to a Geobacillus sp. in the 448.6- to 99.4-mbsf cores and a Deinococcus
      sp. in the 64.8- to 128.9-mbsf cores, respectively, based on the 16S ribosomal
      DNA analysis.

PMID- 12514054
TI  - The spoilage yeast Zygosaccharomyces bailii forms mitotic spores: a screening
      method for haploidization.
AB  - Zygosaccharomyces bailii ISA 1307 and the type strain of this spoilage yeast show
      a diploid DNA content. Together with a rather peculiar life cycle in which
      mitotic but no meiotic spores appear to be formed, the diploid DNA content
      explains the observed difficulties in obtaining auxotrophic mutants. Mitotic
      chromosome loss induced by benomyl and selection on canavanine media resulted in
      three haploid strains of Z. bailii. This new set of Z. bailii strains allows the
      easy isolation of recessive mutants and is suitable for further molecular genetic
      studies.

PMID- 12514055
TI  - Enumeration of bifidobacteria in gastrointestinal samples from piglets.
AB  - The population of Bifidobacterium spp. in fecal samples from suckling piglets was
      investigated, and Beerens, raffinose-bifidobacterium (RB), and modified Wilkins
      Chalgren (MW) agar media were evaluated with regard to the enumeration of
      bifidobacteria in porcine intestinal samples. The results demonstrated that the
      population of bifidobacteria in the feces of suckling piglets is numerically low,
      and a phylogenetic analysis of the 16S rRNA gene from bifidobacterial isolates
      suggested that a possibly new Bifidobacterium species was isolated. Beerens, RB,
      and MW agar media were not selective for bifidobacteria in the fecal samples. The
      highest recovery and diversity of bifidobacteria were obtained for MW agar.
      Nonbifidobacterial isolates from the three agar media were identified and may
      contribute to the future formulation of improved selective media for the
      enumeration of bifidobacteria.

PMID- 12514056
TI  - Effect of associated bacteria on the growth and toxicity of Alexandrium
      catenella.
AB  - Saprophytic bacteria in cultures of the marine dinoflagellate Alexandrium
      catenella were removed to assess their effect on growth and paralytic shellfish
      poisoning toxin production of this dinoflagellate. The actual axenic status was
      demonstrated by the lack of observable bacteria both immediately after treatment
      and following extended incubation in the absence of antibiotics. Bacteria were
      measured by counting CFU and also by epifluorescence microscopy and PCR
      amplification of bacterial 16S-23S spacer ribosomal DNA to detect noncultivable
      bacteria. Removal of bacteria did not have any effect on the growth of the
      dinoflagellate except for the inhibition of A. catenella disintegration after
      reaching the stationary phase. Toxicity was determined in dinoflagellate cell
      extracts by different methods: high-performance liquid chromatography (HPLC); an
      electrophysiological test called the Electrotest, which measures the inhibition
      of saxitoxin-sensitive Na(+) channels expressed in a cell line; and a mouse
      bioassay, which measures the toxic effect on the whole mammal neuromuscular
      system. A lower toxicity of the dinoflagellates in axenic culture was observed by
      these three methods, though the difference was significant only by the mouse
      bioassay and HPLC methods. Altogether the results indicate that axenic cultures
      of A. catenella are able to produce toxin, though the total toxicity is probably
      diminished to about one-fifth of that in nonaxenic cultures.

PMID- 12514057
TI  - A colonization factor (production of lateral flagella) of mesophilic Aeromonas
      spp. is inactive in Aeromonas salmonicida strains.
AB  - The nine laf (lateral flagellum) genes of mesophilic aeromonads are in the
      Aeromonas salmonicida genome. The laf genes are functional, except for lafA
      (flagellin gene), which was inactivated by transposase 8 (IS3 family). A
      pathogenic characteristic of mesophilic aeromonads (lateral flagella) is
      abolished in this specialized pathogen with a narrow host range.

PMID- 12514058
TI  - Inactivation of Salmonella enterica serovar enteritidis by ultrasonic waves under
      pressure at different water activities.
AB  - The inactivation of Salmonella enterica serovar Enteritidis by ultrasonic waves
      (20 kHz; 117- microm wavelength) under pressure (175 kPa) at nonlethal
      temperatures (manosonication [MS]) and lethal temperatures (manothermosonication
      [MTS]) in media of different water activities has been investigated. Heat decimal
      reduction time values increased 30 times when the water activity was decreased
      from nearly 1 to 0.96, but the MS resistance was increased only twofold. The
      inactivation of Salmonella serovar Enteritidis by ultrasound under pressure at
      low water activities was a phenomenon of the "all-or-nothing" type. A synergistic
      lethal effect was observed between heat and ultrasound in media with reduced
      water activity; the lower the water activity, the greater the synergistic effect.
      This work could be useful for improving sanitation and preservation treatments of
      foods, especially those which are sensitive to temperature and those in which
      components protect microorganisms to heat. It also contributes to our knowledge
      of microbial inactivation mechanisms by MS and MTS treatments.

PMID- 12514059
TI  - Degradation and transformability of DNA from transgenic leaves.
AB  - The fate of transplastomic (chloroplast genome contains the transgene) tobacco
      plant DNA in planta was studied when the plant leaves were subjected to decay
      conditions simulating those encountered naturally, including grinding, incubation
      with cellulase or enzymes produced by Erwinia chrysanthemi, and attack by the
      plant pathogen Ralstonia solanacearum. Direct visualization of DNA on agarose
      gels, gene extraction yield (the number of amplifiable aadA sequences in
      extracted plant DNA), and the frequency that recipient bacteria can be
      transformed by plant DNA were used to evaluate the quality and quantity of plant
      DNA and the transgene. These measurements were used to monitor the physical and
      biological degradation of DNA inside decaying plant tissues. Our results indicate
      that while most of the DNA will be degraded inside plant cells, sufficient DNA
      persists to be released into the soil.

PMID- 12514060
TI  - Molecular characterization of natural Erwinia pyrifoliae strains deficient in
      hypersensitive response.
AB  - From necrotic tissue of a Nashi pear tree, 24 Erwinia pyrifoliae strains, found
      to be identical by pulsed-field gel electrophoresis analysis, were isolated.
      Thirteen strains were not virulent on immature pears and did not induce a
      hypersensitive response in tobacco leaves. The defective gene hrpL was
      complemented with intact genes from E. pyrifoliae and Erwinia amylovora.

PMID- 12514061
TI  - Comparison of UV inactivation of spores of three encephalitozoon species with
      that of spores of two DNA repair-deficient Bacillus subtilis biodosimetry
      strains.
AB  - When exposed to 254-nm UV, spores of Encephalitozoon intestinalis,
      Encephalitozoon cuniculi, and Encephalitozoon hellem exhibited 3.2-log reductions
      in viability at UV fluences of 60, 140, and 190 J/m(2), respectively, and
      demonstrated UV inactivation kinetics similar to those observed for endospores of
      DNA repair-defective mutant Bacillus subtilis strains used as biodosimetry
      surrogates. The results indicate that spores of Encephalitozoon spp. are readily
      inactivated at low UV fluences and that spores of UV-sensitive B. subtilis
      strains can be useful surrogates in evaluating UV reactor performance.

PMID- 12514062
TI  - Effect of stress on the ability of a phlA-based quantitative competitive PCR
      assay to monitor biocontrol strain Pseudomonas fluorescens CHA0.
AB  - A quantitative competitive PCR (QC-PCR) assay targeting the phlA gene of
      Pseudomonas fluorescens CHA0 was developed and tested in vitro. Statistically
      significant, positive correlations were found between QC-PCR and both CFU and
      total cell number when studying cells in log or stationary phase. The
      correlations disappeared when considering stressed cells.

PMID- 12514063
TI  - Characteristics of a novel type of bovine Cryptosporidium andersoni.
AB  - We isolated oocysts that resemble Cryptosporidium andersoni from cattle grazing
      on a farm in Japan. The partial sequences of genes from the isolate were
      coincident with published sequences of genes of C. andersoni. Since the isolate
      was able to infect SCID mice, the isolate appears to be a novel type of C.
      andersoni.

PMID- 12514064
TI  - Formyltetrahydrofolate synthetase sequences from salt marsh plant roots reveal a
      diversity of acetogenic bacteria and other bacterial functional groups.
AB  - Sixty-two partial formyltetrahydrofolate synthetase (FTHFS) structural gene
      sequences were recovered from roots of salt marsh plants, including Spartina
      alterniflora, Salicornia virginica, and Juncus roemerianus. Only S. alterniflora
      roots yielded sequences grouping with FTHFS sequences from known acetogens. Most
      other FTHFS or FTHFS-like sequences grouped with those from sulfate-reducing
      bacteria. Several sequences that grouped with Sphingomonas paucimobilis ligH were
      also recovered.

PMID- 12514065
TI  - Molecular typing of Aeromonas isolates in natural mineral waters.
AB  - A total of 103 isolates of Aeromonas spp. were obtained over a 3-year period from
      a natural mineral water and from surface streams located within the boundaries of
      the watershed of the natural mineral water wells and were typed by
      macrorestriction analysis of genomic DNA with XbaI and by pulsed-field gel
      electrophoresis. All Aeromonas caviae isolates from the natural mineral water
      belonged to the same clone, and an analogous clonal identity was found among
      Aeromonas hydrophila isolates. These two clones expressed no hemolytic or
      cytotoxic activities. Aeromonas isolates from surface waters showed high
      molecular heterogeneity and were not related to the clones found in the natural
      mineral water. The presence of aeromonads chronically found in the natural
      mineral water was a likely consequence of a localized development of a biofilm,
      with no exogenous contamination of the aquifer. Molecular fingerprinting of
      drinking water isolates is a useful tool in explaining possible reasons for
      bacterial occurrences.

PMID- 12514066
TI  - A food-grade approach for functional analysis and modification of native plasmids
      in Lactococcus lactis.
AB  - While plasmids from lactic acid bacteria possess many traits that are of
      industrial value, their exploitation is often frustrated by an inability to
      conduct food-grade engineering of native plasmids or to readily screen for their
      transfer. Here we describe a system that uses a RepA(+) temperature-sensitive
      helper plasmid and a RepA(-) cloning vector to overcome these problems while
      maintaining the food-grade status of the native plasmid. This strategy was used
      to precisely delete ltnA1 alone, or in conjunction with ltnA2 (encoding the
      structural proteins of the lantibiotic lacticin 3147), from the native 60.2-kb
      plasmid pMRC01 and to select for the transfer of pMRC01 between Lactococcus
      lactis strains.

PMID- 12514067
TI  - Glutathione S-transferase isoenzymes from Streptomyces griseus.
AB  - An inducible, cytosolic glutathione S-transferase (GST) was purified from
      Streptomyces griseus. GST isoenzymes with pI values of 6.8 and 7.9 used standard
      GST substrates including 1-chloro-2,4-dinitrobenzene. GST had subunit and native
      M(r)s of 24 and 48, respectively, and the N-terminal sequence SMILXYWDIIRGLPAH.

PMID- 12514068
TI  - Survival and resuscitation of ten strains of Campylobacter jejuni and
      Campylobacter coli under acid conditions.
AB  - The culturability of 10 strains of Campylobacter jejuni and Campylobacter coli
      was studied after the bacteria were exposed to acid conditions for various
      periods of time. Campylobacter cells could not survive 2 h under acid conditions
      (formic acid at pH 4). The 10 Campylobacter strains could not be recovered, even
      when enrichment media were used. Viable cells, however, could be detected by a
      double-staining (5-cyano-2,3-ditolyl tetrazolium chloride [CTC]-4',6'-diamidino-2
      phenylindole [DAPI]) technique, demonstrating that the treated bacteria changed
      into a viable but nonculturable (VBNC) form; the number of VBNC forms decreased
      over time. Moreover, some VBNC forms of Campylobacter could be successfully
      resuscitated in specific-free-pathogen fertilized eggs via two routes, amniotic
      and yolk sac injecting.

PMID- 12514069
TI  - Disruption of the CAR1 gene encoding arginase enhances freeze tolerance of the
      commercial baker's yeast Saccharomyces cerevisiae.
AB  - The effect of intracellular charged amino acids on freeze tolerance in dough was
      determined by constructing homozygous diploid arginase-deficient mutants of
      commercial baker's yeast. An arginase mutant accumulated higher levels of
      arginine and/or glutamate and showed increased leavening ability during the
      frozen-dough baking process, suggesting that disruption of the CAR1 gene enhances
      freeze tolerance.

PMID- 12514070
TI  - Savinase is a bactericidal enzyme.

PMID- 12514071
TI  - Adherens junction dynamics in the testis and spermatogenesis.

PMID- 12514072
TI  - Of men (and pigs and goats) in mice?

PMID- 12514073
TI  - Human sperm survival assay as a bioassay for the assisted reproductive
      technologies laboratory.

PMID- 12514074
TI  - Cryptorchidism, fertility, and cancer.

PMID- 12514075
TI  - Outcomes for vasovasostomy with bilateral intravasal azoospermia.
AB  - We conducted an evaluation of outcomes for microsurgical vasectomy reversal in
      which sperm are absent from the vas fluid in order to determine a threshold
      obstructive interval when vasoepididymostomy (VE) may be indicated. Vasectomy
      reversal was performed for 32 patients with intravasal azoospermia: 25 received
      bilateral vasovasostomy (VV), 1 had a bilateral VV, 5 underwent VV/VE, and 1 had
      bilateral VE. Overall, the patency rate was 50% (14 of 28). Five pregnancies
      (20%) and 3 live births (12%) occurred in 25 patients with sufficient follow-up.
      One pregnancy was electively terminated and the other is ongoing, for an ongoing
      or delivered rate of 16%. The patency rate for VV (either bilateral or
      unilateral) was 55% (12 of 22). Median obstructive interval was 7 years in patent
      and 15 years in nonpatent cases, respectively, (P =.0027). Sperm were not
      observed after VV in any case n which the obstructive interval was greater than
      11 years. If VV was limited to obstructive intervals of 11 years or less, then
      the patency rate was 80% (12 of 15) and the pregnancy rate was 38% (5 of 13). The
      patency rate for bilateral VV was 67% (8 of 12) if clear fluid was observed on at
      least one side. We conclude that VE is not required in every case of intravasal
      azoospermia, but it could improve success rates in this setting. Based on our
      experience, VE may be indicated for intravasal azoospermia if the obstructive
      interval is more than 11 years.

PMID- 12514076
TI  - Outcomes for vasovasostomy with bilateral intravasal azoospermia.

PMID- 12514077
TI  - Peyronie disease in younger men: characteristics and treatment results.
AB  - We retrospectively reviewed our experience with 30 men with Peyronie disease (PD)
      younger than age 40 years to describe their clinical presentation, physical
      examination findings, and treatment outcomes. In addition, we performed a
      literature review to define the typical patient with PD and to compare our
      findings with those in the literature. The mean age of our study population was
      31 years (range 18-38 years). The prevalence of patients under the age of 40
      presenting with PD was 1.5%. In this population, 97% reported normal erectile
      capacity, and 100% presented with a palpable plaque. Medical and surgical
      treatments were used in the young population with results comparable to published
      data. According to the published literature we reviewed, patients with PD were
      less likely to recall a specific traumatic event, less likely to complain of
      painful intercourse, they had different directions of penile curvature, and
      different locations of penile plaques. Younger men with PD commonly present with
      complaints and physical examination findings that differ from the typical patient
      with PD.

PMID- 12514078
TI  - Peyronie disease in younger men.

PMID- 12514079
TI  - Outpatient surgery for penile venous patch with the patient under local
      anesthesia.
AB  - Although local anesthesia for penile surgery has been widely reported, its
      application for penile venous patch, however, has not been published. We
      evaluated an anesthetic and surgical technique on an outpatient basis. From March
      1993 to September 2001, a total of 29 men with penile deformity, aged 27 to 77
      years (mean 55 years) received a penile venous patch for morphologic correction.
      They received autologous grafting of the deep dorsal vein under local anesthesia
      as an outpatient procedure. The anesthetic effect and postoperative results were
      satisfactory. The average available area of the deep dorsal vein was 5.7 x 2.5
      cm(2). The common immediate side effects included puncture of the vessels,
      subcutaneous ecchymosis, and transient palpitation, but there were no significant
      late complications. All patients returned home uneventfully. This has been proven
      to be a cost-effective, simple, and safe method with fewer complications. It
      offers the advantages of lower morbidity, protection of privacy, fewer adverse
      effects of anesthesia, and a more rapid return to activity with minimal
      complications.

PMID- 12514080
TI  - Outpatient surgery for penile venous patch with the patient under local
      anesthesia.

PMID- 12514081
TI  - Clinical and diagnostic features of patients with suspected Klinefelter syndrome.
AB  - Klinefelter syndrome, with an incidence of 1:600 male newborns, is the most
      frequent form of male hypogonadism. However, despite its relatively high
      frequency, the syndrome is often overlooked. To prevent such oversights, the
      clinical features should be better characterized, and simple screening tests
      should be used more frequently. In a cohort of 309 patients suspected of having
      Klinefelter syndrome, we evaluated the clinical symptoms as well as the
      diagnostic value of the Barr body test for screening procedures. On the basis of
      chromosome analysis, 85 patients (group I) were diagnosed as having Klinefelter
      syndrome, and 224 patients had a 46,XY karyotype (group II). Barr body analysis
      revealed a specificity of 95% and a sensitivity of 82% for the diagnosis of
      Klinefelter syndrome. General features (eg, reason for admission, age, age of the
      parents, body weight, and frequency of maldescended testes) were not different
      between the groups, except that group I had a higher proportion of patients with
      a lower educational background. Compared to group II, patients with Klinefelter
      syndrome were taller (P <.001); had smaller testis volumes (P <.0001), higher
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH) values; and
      carried a tendency for less androgenic phenotype and secondary hair distribution.
      Testosterone, estradiol, sex hormone-binding globulin (SHBG), and prostate
      specific antigen (PSA) serum levels as well as prostate volume were not
      significantly different between the groups. In patients who provided an
      ejaculate, azoospermia was found in 54% of the patients in group II and in 93% of
      the patients with Klinefelter syndrome. Although not exclusively characteristic
      for Klinefelter syndrome, the combination of low testicular volume and
      azoospermia, together with elevated gonadotropins, is highly indicative for a
      Klinefelter syndrome and should stimulate further clinical investigations. Barr
      body analysis provides a quick and reliable screening test, which, however, must
      be confirmed by karyotyping.

PMID- 12514082
TI  - Clinical and diagnostic features of patients with suspected Klinefelter syndrome.

PMID- 12514083
TI  - Mouse epididymal Spam1 (pH-20) is released in the luminal fluid with its lipid
      anchor.
AB  - Previously we demonstrated that the murine sperm adhesion molecule 1 (Spam1 or PH
      20) is synthesized by the epididymal epithelium, preferentially in the distal
      region, and is released into the luminal fluid. We also showed that whereas
      testicular and epididymal Spam1 have hyaluronidase activity at neutral pH, they
      are under different transcriptional regulation. The aim of this study was to
      further compare characteristics of the two forms of this glycosyl
      phosphatidylinositol-linked protein and their transcripts, and to determine
      whether secreted epididymal Spam1 is released with its lipid anchor. With
      GeneRacer amplification of the 3' end of the complementary DNA we show that the
      poly(A) tails are significantly (P <.05) shorter in the epididymis than in the
      testis. Two-dimensional polyacrylamide gel electrophoresis with immunoblotting
      reveals one to three isoforms for epididymal Spam1 with the isoelectric point
      (pl) ranging from 7.3 to 9.0, and four isoforms ranging from 6.6 to 9.0 pl for
      testicular Spam1. Two isoforms with a pl ranging from 7.6 to 9.0 were observed
      for caudal sperm. Lectin blotting analysis shows that Phaseolus vulgaris
      erythroagglutinin, Lycopersicon esculentum lectin (LEL), and Solanum tuberosum
      lectin, which all bind to N-linked chains, recognize a 67 kd band in the
      epididymis and caudal sperm, but not in the testis. Treatment of the protein
      extracts with anti-Spam1 serum prior to blotting with LEL led to the
      disappearance of the banding, indicating Spam1 specificity of the staining. The
      lectin peanut agglutinin, which preferentially binds to O-linked side chains,
      recognizes a 67 kd band in all three cell types. Enzymatic deglycosylation
      studies confirmed the presence of an O-linked glycan in all three cell types.
      Ultracentrifugation of the luminal fluid reveals that epididymal Spam1 is
      secreted predominantly as insoluble particles, which when treated with
      phosphatidylinositol-specific phospholipase C or Triton X-100, reveal that the
      majority of epididymal Spam1 is released with its lipid anchor, a form in which
      it can bind to sperm.

PMID- 12514084
TI  - The sperm chromatin dispersion test: a simple method for the determination of
      sperm DNA fragmentation.
AB  - Sperm DNA fragmentation is being increasingly recognized as an important cause of
      infertility. We herein describe the Sperm Chromatin Dispersion (SCD) test, a
      novel assay for sperm DNA fragmentation in semen. The SCD test is based on the
      principle that sperm with fragmented DNA fail to produce the characteristic halo
      of dispersed DNA loops that is observed in sperm with non-fragmented DNA,
      following acid denaturation and removal of nuclear proteins. This was confirmed
      by the analysis of DNA fragmentation using the specific DNA Breakage Detection
      Fluorescence In Situ Hybridization (DBD-FISH) assay, which allows the detection
      of DNA breaks in lysed sperm nuclei. Sperm suspensions either prepared from semen
      or isolated from semen by gradient centrifugation were embedded in an agarose
      microgel on slides and treated with 0.08 N HCl and lysing solutions containing
      0.8 M dithiothreitol (DTT), 1% sodium dodecyl sulfate (SDS), and 2 M NaCl. Then,
      the slides were sequentially stained with DAPI (4',6-diamidino-2-phenylindole)
      and/or the Diff-Quik reagent, and the percentages of sperm with nondispersed and
      dispersed chromatin loops were monitored by fluorescence and brightfield
      microscopy, respectively. The results indicate that all sperm with nondispersed
      chromatin displayed DNA fragmentation, as measured by DBD-FISH. Conversely, all
      sperm with dispersed chromatin had very low to undetectable DBD-FISH labeling.
      SCD test values were significantly higher in patients being screened for
      infertility than in normozoospermic sperm donors who had participated in a donor
      insemination program. The coefficient of variation obtained using 2 different
      observers, either by digital image analysis (DIA) or by brightfield microscopy
      scoring, was less than 3%. In conclusion, the SCD test is a simple, accurate,
      highly reproducible, and inexpensive method for the analysis of sperm DNA
      fragmentation in semen and processed sperm. Therefore, the SCD test could
      potentially be used as a routine test for the screening of sperm DNA
      fragmentation in the andrology laboratory.

PMID- 12514085
TI  - Effect on clinical outcome of the interval between collection of epididymal and
      testicular spermatozoa and intracytoplasmic sperm injection in obstructive
      azoospermia.
AB  - We wished to determine whether the interval between surgical retrieval of
      epididymal and testicular spermatozoa in obstructive azoospermia and their
      subsequent use in intracytoplasmic sperm injection (ICSI) has an effect on their
      fertilizing capacity and pregnancy rates in patients undergoing ICSI. This was a
      retrospective review of 164 consecutive cycles of ICSI in partners of men
      undergoing surgical sperm retrieval for obstructive azoospermia. Seventy-three
      cycles used fresh testicular spermatozoa; in 35 cycles ICSI was performed within
      4 hours of sperm retrieval, and in 38 cycles spermatozoa were incubated overnight
      before ICSI. Epididymal spermatozoa were used in 29 cycles; 22 cases within 4
      hours of retrieval and 7 cases following overnight culture. Cyropreserved
      testicular and epididymal spermatozoa were used in 42 and 20 ICSI cycles,
      respectively. Fertilization and clinical pregnancy rates were calculated for each
      treatment group. Fertilization rates for epididymal spermatozoa were 67% at 4
      hours, 56% at 24 hours, and 63% for cryopreserved spermatozoa (P =.52).
      Fertilization rates for testicular spermatozoa were 63% at 4 hours, 71% at 24
      hours, and 60% for cryopreserved spermatozoa (P =.16). Unlike testicular
      spermatozoa, cryopreserved epididymal spermatozoa showed a significant increase
      in clinical pregnancy rates with cryopreservation, with rates of 4 of 22, 1 of 7,
      and 10 of 20 at 4 hours, 24 hours, and cryopreservation, respectively (P =.049).
      This study confirms that fertilization and pregnancy rates following ICSI with
      motile spermatozoa are unaffected by the duration between surgical retrieval of
      spermatozoa and their injection into oocytes. It also demonstrates that of all
      treatment modalities, the use of frozen epididymal spermatozoa was associated
      with the greatest pregnancy rates.

PMID- 12514086
TI  - Complexes of gelatinases and tissue inhibitor of metalloproteinases in human
      seminal plasma.
AB  - Previously reported data have indicated the existence of two kinds of matrix
      metalloproteinases (MMP-2 and MMP-9) in human seminal plasma (Shimokawa et al,
      2002). Here we report the existence of complexes of gelatinases and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in human seminal plasma.
      After the seminal plasma supernatant was separated on a gel-filtration column
      chromatography of GCL-2000-sf-cellulofine. Western blot analysis showed these
      proteins were recognized by two antibodies to TIMP-1 and TIMP-2, but not to TIMP
      3 or TIMP-4. These bands were consistent with standard recombinant full-length
      TIMP-1 and TIMP-2 proteins. These bands had molecular weights of approximately 29
      and 21 kd for TIMP-1 and TIMP-2, respectively. These proteins existed as
      complexes of proMMP-9/TIMP-1, proMMP-2/TIMP-2, MMP-2/TIMP-2, free TIMP-1, and
      TIMP-2 in human seminal plasma. The partially free TIMPs were degradated by some
      proteinases in human seminal plasma. These results indicate two kinds of TIMPs
      (TIMP-1 and TIMP-2) and their complexes with progelatinases in human seminal
      plasma.

PMID- 12514087
TI  - Lack of RBM expression as a marker for carcinoma in situ of prepubertal
      dysgenetic testis.
AB  - Individuals with various intersex states who carry Y-chromosome material bear a
      high risk of developing testicular neoplasia. In order to gain more insight into
      the pathogenesis of this neoplasia, the current study evaluates the
      differentiation of the seminiferous epithelium in 46,XY dysgenetic male
      pseudohermaphroditism. Immunohistochemical evaluation was performed using the
      germ cell-specific RNA-binding motif (RBM) protein (encoded by the Y-chromosome)
      to identify normal germ cells, whereas placental alkaline phosphatase (PLAP) was
      used to detect neoplastic germ cells. Differentiation of somatic Sertoli cells
      was assessed using cytokeratin-18 (CK-18) and anti-Mullerian hormone (AMH) as
      markers for immature Sertoli cells. Specimens were taken from surgically removed
      dysgenetic gonads of five children (46XY karyotype). Intratubular germ cell
      neoplasia (carcinoma in situ [CIS] of the testis) was detected in all of them.
      Normal germ cells revealed immunoreactivity for RBM, whereas the PLAP-positive
      neoplastic germ cells were negative for RBM expression. Sertoli cells revealed an
      immature phenotype indicated by AMH expression in their cytoplasm. The design of
      the current study is unique in its assessment of the state of germ cell
      differentiation in dysgenetic gonads by the use of the RBM protein, which was
      expressed only in normal germ cells but not in those of CIS. Testicular
      dysgenesis interrupted the normal differentiation of the germ line and had no
      effect on the immature phenotype of the prepubertal Sertoli cells. This points
      toward the germinal component of CIS as the precursor for the promotion of testis
      cancer.

PMID- 12514088
TI  - Ex vivo expression of angiogenic growth factors and their receptors in human
      penile cavernosal cells.
AB  - Arteriogenic erectile dysfunction is associated with impairment of vascular
      perfusion to the erectile components of the penis. Animal studies have identified
      insulin-like growth factor (IGF-I) and vascular endothelial growth factor (VEGF)
      as penile angiogenic growth factors, but the role of these factors in humans is
      not well understood. We evaluated the ex vivo expression of IGF-I, VEGF, and
      their receptors (IGF-IR, Flt-1, and KDR) in human penile cavernosal smooth muscle
      cells (HCSMCs) to identify cellular and molecular pathways involved in the
      regulation of penile tissue vascularity. Primary culture was initiated with
      explants of human corpora cavernosa, and early passage (3-5) cells were used for
      these evaluations. Cultures were examined to verify the presence of smooth muscle
      cells and the absence of endothelial cell contamination. Specific monoclonal
      antibodies were used to localize growth factors and their receptors. To evaluate
      gene expression of VEGF, Flt-1, and KDR, total RNA was extracted from cavernosal
      cells and subjected to reverse transcriptase-polymerase chain reaction (RT-PCR)
      using custom synthesized primers. To study the effect on cell proliferation,
      10000 cells/well were exposed to varying concentrations of VEGF (0-50 ng/mL). At
      specified time periods the cells were trypsinized and counted. IGF-I and VEGF and
      their receptors were localized in the cultures, which were positive for the
      presence of smooth muscle cells and negative for endothelial cell contamination.
      RT-PCR evaluation revealed the expression of four splice variants of VEGF
      messenger RNA (VEGFs 121, 145, 165, and 189) and two of its receptors (Flt-1 and
      KDR). VEGF165 and VEGF121 were the most abundant forms of messenger RNA and Flt-1
      appeared to be the most prominent receptor type in these cells. Exposure to VEGF
      elicited a twofold to threefold increase in the proliferation of HCSMCs. HCSMCs
      express both IGF-I and VEGF and their receptors, which may be important in the
      control of vascularity in human penile architecture.

PMID- 12514089
TI  - Involvement of cytoplasmic free calcium in boar sperm: head-to-head agglutination
      induced by a cell-permeable cyclic adenosine monophosphate analog.
AB  - When boar spermatozoa are incubated in a medium designed for in vitro
      fertilization, many of them become agglutinated at the acrosomes. We previously
      reported that bicarbonate and cyclic adenosine 3',5'-monophosphate (cAMP) promote
      agglutination. The aim of the present study is to examine the role of cytoplasmic
      free Ca(2+) in boar sperm agglutination induced by a cell-permeable cAMP
      analogue. Spermatozoa were collected from five mature boars, washed, and
      resuspended in a modified Krebs-Ringer-Hepes solution lacking calcium chloride.
      The sperm suspensions were incubated in a water bath (38.5 degrees C) for 60
      minutes and were then used to determine the percentages of head-to-head
      agglutinated spermatozoa. Percentages of head-to-head agglutinated spermatozoa in
      the samples rose significantly after incubation, from 28% to 61%-62%, after
      adding to the medium a cell-permeable, phosphodiesterase-resistant cAMP analogue
      (cBiMPS, 10 microM) or an adenylyl cyclase stimulator (sodium bicarbonate, 5 mM)
      plus a cell-permeable phosphodiesterase inhibitor (IBMX, 25 microM). However, the
      promoting effects of these reagents were blocked when spermatozoa were pretreated
      with a cell-permeable Ca(2+) chelator (BAPTA-AM, 25 microM), whereas the same
      pretreatment with a cell-impermeable Ca(2+) chelator (BAPTA, 25 microM) had
      almost no influence on sperm agglutination. Adding thapsigargin, a potential
      Ca(2+)-ATPase inhibitor, to the medium raised the percentages of agglutinated
      spermatozoa in a concentration-dependent manner for concentrations up to 4
      microM. When 4 microM thapsigargin and 10 microM cBiMPS were examined for their
      effects on free Ca(2+) levels in sperm heads by using a cell-permeable Ca(2+)
      indicator (fluo-3/AM), the samples incubated with both or either of these
      reagents contained many head-to-head agglutinated cells that exhibited intense
      fluorescence in the heads. In control samples incubated without these reagents by
      contrast, most spermatozoa were free (unagglutinated) cells and characterized by
      almost no or only slight fluorescence in the heads. Moreover, morphological
      observation of Giemsa-stained preparations revealed that most agglutinated
      spermatozoa possessed darkly stained acrosomes, which distinguished them from
      acrosomereacted spermatozoa. This indicated that the sperm agglutination was not
      a result of the acrosome reaction. Furthermore, with indirect immunofluorescence
      of Ca(2+)-ATPases, the mouse monoclonal antibody to this enzyme demonstrated high
      affinity to the acrosomes of permeabilized spermatozoa. Based on these results,
      we conclude that cytoplasmic free Ca(2+) is involved in sperm head-to-head
      agglutination induced by a cAMP analogue.

PMID- 12514090
TI  - Analysis of aneuploidy in spermatozoa from testicular biopsies from men with
      nonobstructive azoospermia.
AB  - Testicular sperm biopsy combined with intracytoplasmic sperm injection (ICSI)
      allows men with azoospermia the possibility of fathering a child. However, little
      information exists on the risk of chromosome abnormalities in their sperm.
      Multicolor fluorescence in situ hybridization (FISH) analysis was used to
      determine the frequency of sperm diploidy and disomy for the sex chromosomes in
      six men with normal karyotypes and non-obstructive azoospermia. A new method
      using microwave decondensation and codenaturation of sperm nuclei yielded a much
      larger number of sperm nuclei for FISH analysis than our previous study of men
      with azoospermia. A total of 59916 sperm were analyzed; more than 9000 sperm were
      scored for each man. The men with nonobstructive azoospermia had an increased
      frequency of sperm chromosomal disomy for YY, XY, total sex chromosomal disomy,
      and diploidy compared with 18 normal controls, but only YY disomy reached
      statistical significance. One infertile man had a frequency of 3.8% XY disomy and
      4.3% diploidy, which was 13-fold and 7-fold higher than control donors,
      respectively. Our results suggest that some men with nonobstructive azoospermia
      have a significantly increased frequency of sex chromosomal abnormalities than
      normal men, but that the overall frequency of abnormalities is similar to that
      found in infertile men with abnormal semen parameters.

PMID- 12514091
TI  - Implication of calmodulin-dependent phosphodiesterase type 1 during bovine sperm
      capacitation.
AB  - Phosphodiesterases (PDEs) are enzymes that degrade cyclic nucleotides. The
      calcium-calmodulin dependent PDE type 1 (PDE 1) and the cyclic adenosine
      monophosphate (cAMP)-specific PDE type 4 (PDE 4) have been implicated in sperm
      function. We tested the hypothesis that specific PDEs regulate capacitation of
      bovine sperm in a manner independent of those that mediate motility. Our
      objectives were to determine the effects of inhibiting PDE 1 and PDE 4 on
      capacitation and motility, and to compare these effects to those of heparin,
      which is necessary for capacitation of bull sperm in vitro. Fresh sperm were
      supplemented either with 15 microg/mL heparin (positive control) or the PDE
      inhibitors vinpocetine (specific for PDE 1) and rolipram (specific for PDE 4),
      and then incubated for 5 hours. At 0, 3, and 5 hours, samples were assayed for
      capacitation and motility parameters according to the chlortetracycline (CTC)
      fluorescent pattern B and computer-assisted sperm analysis, respectively. A
      higher percentage of CTC pattern B sperm relative to heparin controls was
      observed at 0 and 3 hours when sperm were incubated with vinpocetine. After 5
      hours, the percentage of heparin- and vinpocetine-treated sperm showing pattern B
      did not differ (P >.05). Rolipram did not affect CTC patterns (P >.05; n = 4).
      Vinpocetine and heparin both reduced the percentage of progressively motile sperm
      after 3 and 5 hours, but vinpocetine reduced it more than heparin (P <.05; n =
      4). Rolipram transiently increased linearity versus sperm with heparin (P <.05; n
      = 4). To further test the hypothesis that PDE 1 inhibition permits capacitation,
      we conducted in vitro fertilization. Vinpocetine did not support the ability of
      sperm to penetrate homologous oocytes (n = 5). Although cAMP regulation by PDE 1
      may occur early during capacitation, downstream events appear to prevent full
      capacitation from occurring prematurely.

PMID- 12514092
TI  - Immunohistochemical detection of the retinoid X receptors alpha, beta, and gamma
      in human prostate.
AB  - The aim of this study was to evaluate the presence and distribution of retinoid X
      receptors (RXRs) alpha, beta, and gamma in normal, hyperplastic (nodular, basal
      cell, and atrophic hyperplasia), and carcinomatous human prostates in order to
      elucidate the relationship among these receptors and the onset and development of
      prostatic adenocarcinoma. RXRalpha and RXRgamma were immunodetected in all
      samples of normal, nodular, and basal cell hyperplasia, as well as carcinomatous
      prostates. In atrophic glands, the expression of both receptors was found in
      22.5% of samples. Positive immunostaining for RXRbeta was observed in 53.3% of
      normal prostates, 100% of samples showed basal cell hyperplasia, and were
      negative in nodular and atrophic hyperplasia. In prostatic adenocarcinoma, only 3
      of 25 samples (the 3 diagnosed as well-differentiated) were positive for RXRbeta.
      Results suggest that diminished RXRbeta expression might be related to prostate
      cancer progression and because the responsiveness to retinoic acid treatments
      depends on the expression of different receptors, it is important to study their
      expression before therapy.

PMID- 12514093
TI  - Establishment and characterization of neonatal mouse sertoli cell lines.
AB  - Sertoli cells isolated from 6-day postpartum mouse testes were conditionally
      immortalized with the simian virus 40 large tumor antigen gene (SV40-LTAg) under
      the control of a promoter inducible with ponasterone A, an analog of ecdysone.
      This strategy produced 2 cell lines, which exhibited mixed phenotypes. We first
      tested the conditional expression of the LTAg gene in the presence or absence of
      ponasterone A. The results showed that both cell lines expressed LTAg when the
      inducer was present in the culture media. When ponasterone A was removed, the
      majority of the cells died. After 60 generations, however, the continued
      expression of LTAg in the absence of the hormone indicated that unknown changes
      may have occurred in the genome of the cells. One of the cell lines was further
      subcloned, resulting in 7 new lines exhibiting a morphology resembling that of
      Sertoli cells in tissue culture. Reverse transcriptase-polymerase chain reaction
      (RT-PCR) was performed on RNA collected from each cell line in order to determine
      which cells were phenotypically similar to Sertoli cells in vivo. All cell lines
      expressed the products of the Sertoli cell-specific genes stem cell factor (SCF)
      and sulfated glycoprotein-2 (SGP-2), in addition to alpha-inhibin, GATA-1, and
      steroidogenic factor-1. Further, the lines express growth and differentiation
      factors known to act upon germ cells in vivo and in vitro such as leukemia
      inhibitory factor (LIF), transforming growth factor beta (TGF-beta), and basic
      fibroblast growth factor (bFGF). Moreover, when used as feeder layers in
      cocultures, at least 2 of these lines are able to maintain the viability of type
      A spermatogonia for at least 7 days and to support the first steps of
      spermatogonial differentiation.

PMID- 12514094
TI  - A two-cilia model for vertebrate left-right axis specification.

PMID- 12514095
TI  - The ADAMs family of metalloproteases: multidomain proteins with multiple
      functions.

PMID- 12514096
TI  - EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1.
AB  - The TGF-beta signals Nodal, Activin, GDF1, and Vg1 have been implicated in
      mesoderm induction and left-right patterning. Nodal and Activin both activate
      Activin receptors, but only Nodal requires EGF-CFC coreceptors for signaling. We
      report that Vg1 and GDF1 signaling in zebrafish also depends on EGF-CFC proteins,
      but not on Nodal signals. Correspondingly, we find that in Xenopus Vg1 and GDF1
      bind to and signal through Activin receptors only in the presence of EGF-CFC
      proteins. These results establish that multiple TGF-beta signals converge on
      Activin receptor/EGF-CFC complexes and suggest a more widespread requirement for
      coreceptors in TGF-beta signaling than anticipated previously.

PMID- 12514097
TI  - Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene
      segments.
AB  - Pax5-deficient progenitor B (pro-B) cells are thought to be severely defective
      for recombination of all immunoglobulin heavy chain (IgH) V gene segments, but
      the mechanism by which Pax5 regulates this process has not been defined. To
      address this issue, we have examined the assembly of the IgH locus in Pax5
      deficient pro-B cells and find, unexpectedly, that 3' IgH V gene segments, which
      lie closest to the D-J-Cmu region, recombine efficiently, but progressively more
      distal V gene segments recombine progressively less efficiently. Histone
      acetylation and germ-line transcription correlate strongly with an open or an
      accessible chromatin structure thought to be permissive for V(D)J recombination,
      and defects in recombination are typically accompanied by deficits in these
      processes. We were therefore surprised to observe that distal V(H) gene segments
      in Pax5-/- pro-B cells exhibit no defect in these measures of accessibility. The
      finding of transcribed, histone acetylated gene segments that fail to recombine
      suggests that a Pax5-dependent regulatory mechanism is required in addition to
      standard constraints of accessibility to control V(H) gene recombination.

PMID- 12514098
TI  - Phosphorylation of histone H3 during transcriptional activation depends on
      promoter structure.
AB  - Covalent modifications of histone N-terminal tails are required for the proper
      assembly and activation of the general transcription factors at promoters. Here,
      we analyze histone acetylation and phosphorylation in Drosophila transgenes
      activated by the yeast Gal4 transcriptional activator in the context of different
      promoters. We show that, independent of the promoter, transcription does not
      correlate with acetylation of either H3-Lys 14 or H4-Lys 8. Histone H3 associated
      with the DNA of Gal4-induced transcribing transgenes driven by the Drosophila
      Hsp70 promoter is hyperphosphorylated at Ser 10 during transcription.
      Surprisingly, histone H3 at Gal4-induced transgenes driven by the P element
      Transposase promoter is not hyperphosphorylated. The data suggest that
      transcription occurs without acetylated H4 and H3 in both transgenes in
      Drosophila polytene chromosomes. Instead, phosphorylation of H3 is linked to
      transcription and can be modulated by the structure of the promoter.

PMID- 12514099
TI  - A biochemical framework for RNA silencing in plants.
AB  - RNA silencing phenomena were first discovered in plants, yet only the RNA
      interference pathway in animals has been subject to biochemical analysis. Here,
      we extend biochemical analysis to plant RNA silencing. We find that standard
      wheat germ extract contains Dicer-like enzymes that convert double-stranded RNA
      (dsRNA) into two classes of small interfering RNAs, as well as an RNA-dependent
      RNA polymerase activity that can convert exogenous single-stranded RNA into
      dsRNA. In this plant embryo extract, an endogenous microRNA (miRNA) that lacks
      perfect complementarity to its RNA targets nonetheless acts as a small
      interfering RNA. The miRNA guides an endonuclease to cleave efficiently wild-type
      Arabidopsis PHAVOLUTA mRNA, but not a dominant mutant previously shown to perturb
      leaf development. This finding supports the view that plant miRNAs direct RNAi
      and that miRNA-specified mRNA destruction is important for proper plant
      development. Thus, endonuclease complexes guided by small RNAs are a common
      feature of RNA silencing in both animals and plants.

PMID- 12514100
TI  - Checkpoint activation regulates mutagenic translesion synthesis.
AB  - Cells have evolved checkpoint responses to arrest or delay the cell cycle,
      activate DNA repair networks, or induce apoptosis after genomic perturbation.
      Cells have also evolved the translesion synthesis processes to tolerate genomic
      lesions by either error-free or error-prone repair. Here, we show that after a
      replication perturbation, cells exhibit a mutator phenotype, which can be
      significantly affected by mutations in the checkpoint elements Cds1 and Rad17 or
      translesion synthesis polymerases DinB and Polzeta. Cells respond to genomic
      perturbation by up-regulation of DinB in a checkpoint activation-dependent
      manner. Moreover, association of DinB with chromatin is dependent on functional
      Rad17, and DinB physically interacts with the checkpoint-clamp components Hus1
      and Rad1. Thus, translesion synthesis is a part of the checkpoint response.

PMID- 12514101
TI  - Yeast DNA polymerase zeta (zeta) is essential for error-free replication past
      thymine glycol.
AB  - DNA polymerase zeta (Polzeta) promotes the mutagenic bypass of DNA lesions in
      eukaryotes. Genetic studies in Saccharomyces cerevisiae have indicated that
      relative to the contribution of other pathways, Polzeta makes only a modest
      contribution to lesion bypass. Intriguingly, however, disruption of the REV3
      gene, which encodes the catalytic subunit of Polzeta, causes early embryonic
      lethality in mice. Here, we present genetic and biochemical evidence for the
      requirement of yeast Polzeta for predominantly error-free replication past
      thymine glycol (Tg), a DNA lesion formed frequently by free radical attack. These
      results raise the possibility that, as in yeast, in higher eukaryotes also,
      Polzeta makes a major contribution to the replicative bypass of Tgs as well as
      other lesions that block synthesis by replicative DNA polymerases. Such a
      preeminent role of Polzeta in lesion bypass would ensure that rapid cell
      divisions continue unabated during early embryonic development, thereby
      minimizing the generation of DNA strand breaks, chromosome aberrations, and the
      ensuing apoptotic response.

PMID- 12514102
TI  - Telomere-based crisis: functional differences between telomerase activation and
      ALT in tumor progression.
AB  - Telomerase activation is a common feature of most advanced human cancers and is
      postulated to restore genomic stability to a level permissive for cell viability
      and tumor progression. Here, we used genetically defined transformed mouse
      embryonic fibroblast (MEF) cultures derived from late generation mTerc(-/-)
      Ink4a/Arf(-/-) mice to explore more directly how telomere-based crisis relates to
      the evolution of cancer cell genomes and to tumor biology. An exhaustive serial
      analysis of cytogenetic profiles over extensive passage in culture revealed that
      the emergence of chromosomal fusions (including dicentrics) coincided with onset
      of deletions and complex nonreciprocal translocations (NRTs), whereas mTerc
      transduced cultures maintained intact chromosomes and stable genomes. Despite a
      high degree of telomere dysfunction and genomic instability, transformed late
      passage mTerc(-/-) Ink4a/Arf(-/-) cultures retained the capacity to form
      subcutaneous tumors in immunocompromised mice. However, even moderate levels of
      telomere dysfunction completely abrogated the capacity of these cells to form
      lung metastases after tail-vein injection, whereas mTerc reconstitution alone
      conferred robust metastatic activity in these cells. Finally, serial subcutaneous
      tumor formation using late passage transformed mTerc(-/-) Ink4a/Arf(-/-) cultures
      revealed clear evidence of telomerase-independent alternative lengthening of
      telomeres (ALT). Significantly, despite a marked increase in telomere reserve,
      cells derived from the ALT+ subcutaneous tumors were unable to generate lung
      metastases, indicating in vivo functional differences in these principal
      mechanisms of telomere maintenance. Together, these results are consistent with
      the model that although telomere dysfunction provokes chromosomal aberrations
      that initiate carcinogenesis, telomerase-mediated telomere maintenance enables
      such initiated cells to efficiently achieve a fully malignant endpoint, including
      metastasis.

PMID- 12514103
TI  - The highly conserved Ndc80 complex is required for kinetochore assembly,
      chromosome congression, and spindle checkpoint activity.
AB  - We show that the Xenopus homologs of Ndc80/Tid3/HEC1 (xNdc80) and Nuf2/MPP1/Him
      10 (xNuf2) proteins physically interact in a 190-kD complex that associates with
      the outer kinetochore from prometaphase through anaphase. Injecting function
      blocking antibodies to either xNdc80 or xNuf2 into XTC cells caused premature
      exit from mitosis without detectable chromosome congression or anaphase
      movements. Injected cells did not arrest in response to microtubule drugs,
      showing that the complex is required for the spindle checkpoint. Kinetochores
      assembled in Xenopus extracts after immunodepletion of the complex did not
      contain xRod, xZw10, xP150 glued (Dynactin), xMad1, xMad2, xBub1, and xBub3,
      demonstrating that the xNdc80 complex is required for functional kinetochore
      assembly. In contrast, function-blocking antibodies did not affect the
      localization of other kinetochore proteins when added to extracts containing
      previously assembled kinetochores. These extracts with intact kinetochores were
      deficient in checkpoint signaling, suggesting that the Ndc80 complex participates
      in the spindle checkpoint. We also demonstrate that the spindle checkpoint can
      arrest budding yeast cells lacking Ndc80 or Nuf2, whereas yeast lacking both
      proteins fail to arrest in mitosis. Systematic deletion of yeast kinetochore
      genes suggests that the Ndc80 complex has a unique role in spindle checkpoint
      signaling. We propose that the Ndc80 complex has conserved roles in kinetochore
      assembly, chromosome congression, and spindle checkpoint signaling.

PMID- 12514104
TI  - Nitric oxide contributes to induction of innate immune responses to gram-negative
      bacteria in Drosophila.
AB  - Studies in mammals uncovered important signaling roles of nitric oxide (NO), and
      contributions to innate immunity. Suggestions of conservation led us to explore
      the involvement of NO in Drosophila innate immunity. Inhibition of nitric oxide
      synthase (NOS) increased larval sensitivity to gram-negative bacterial infection,
      and abrogated induction of the antimicrobial peptide Diptericin. NOS was up
      regulated after infection. Antimicrobial peptide reporters revealed that NO
      triggered an immune response in uninfected larvae. NO induction of Diptericin
      reporters in the fat body required immune deficiency (imd) and domino. These
      findings show that NOS activity is required for a robust innate immune response
      to gram-negative bacteria, NOS is induced by infection, and NO is sufficient to
      trigger response in the absence of infection. We propose that NO mediates an
      early step of the signal transduction pathway, inducing the innate immune
      response upon natural infection with gram-negative bacteria.

PMID- 12514105
TI  - Multipotent cell lineages in early mouse development depend on SOX2 function.
AB  - Each cell lineage specified in the preimplantation mammalian embryo depends on
      intrinsic factors for its development, but there is also mutual interdependence
      between them. OCT4 is required for the ICM/epiblast lineage, and at transient
      high levels for extraembryonic endoderm, but also indirectly through its role in
      regulating Fgf4 expression, for the establishment and proliferation of
      extraembryonic ectoderm from polar trophectoderm. The transcription factor SOX2
      has also been implicated in the regulation of Fgf4 expression. We have used gene
      targeting to inactivate Sox2, examining the phenotypic consequences in mutant
      embryos and in chimeras in which the epiblast is rescued with wild-type ES cells.
      We find a cell-autonomous requirement for the gene in both epiblast and
      extraembryonic ectoderm, the multipotent precursors of all embryonic and
      trophoblast cell types, respectively. However, an earlier role within the ICM may
      be masked by the persistence of maternal protein, whereas the lack of SOX2 only
      becomes critical in the chorion after 7.5 days postcoitum. Our data suggest that
      maternal components could be involved in establishing early cell fate decisions
      and that a combinatorial code, requiring SOX2 and OCT4, specifies the first three
      lineages present at implantation.

PMID- 12514106
TI  - Fgfr1 regulates patterning of the pharyngeal region.
AB  - Development of the pharyngeal region depends on the interaction and integration
      of different cell populations, including surface ectoderm, foregut endoderm,
      paraxial mesoderm, and neural crest. Mice homozygous for a hypomorphic allele of
      Fgfr1 have craniofacial defects, some of which appeared to result from a failure
      in the early development of the second branchial arch. A stream of neural crest
      cells was found to originate from the rhombomere 4 region and migrate toward the
      second branchial arch in the mutants. Neural crest cells mostly failed to enter
      the second arch, however, but accumulated in a region proximal to it. Both rescue
      of the hypomorphic Fgfr1 allele and inactivation of a conditional Fgfr1 allele
      specifically in neural crest cells indicated that Fgfr1 regulates the entry of
      neural crest cells into the second branchial arch non-cell-autonomously. Gene
      expression in the pharyngeal ectoderm overlying the developing second branchial
      arch was affected in the hypomorphic Fgfr1 mutants at a stage prior to neural
      crest entry. Our results indicate that Fgfr1 patterns the pharyngeal region to
      create a permissive environment for neural crest cell migration.

PMID- 12514107
TI  - Lifelong caloric restriction increases expression of apoptosis repressor with a
      caspase recruitment domain (ARC) in the brain.
AB  - Aging may increase apoptotic events and the susceptibility of the central nervous
      system to apoptosis. Calorie restriction has been shown to have neuroprotective
      effects, but the mechanisms in vivo are unknown. We investigated apoptosis and
      apoptotic regulatory proteins in the brain frontal cortex of 12-month-old ad
      libitum fed, 26-month-old ad libitum fed, and 26-month-old calorie-restricted
      (CR) male Fischer 344 rats (CR = 40% restricted compared to ad libitum). We found
      that specific DNA fragmentation indicative of apoptosis was increased with age
      (+124%) in the cortices of the brain and that calorie restriction attenuated this
      increase significantly (-36%). We determined levels of ARC (apoptosis repressor
      with a caspase recruitment domain), which inhibits caspase-2 activity and also
      attenuates cytochrome c release from the mitochondria. We found a significant age
      associated decline in ARC level, which was attenuated in the brains of the CR
      rats. In accordance with the changes in ARC expression observed, calorie
      restriction attenuated the increases in cytosolic cytochrome c and caspase-2
      activity with age and suppressed the age-associated rise in cleaved caspase-9 and
      cleaved caspase-3. However, neither age nor calorie restriction had any effect on
      caspase-3 and caspase-9 activities. This data provides evidence for an increased
      incidence of apoptosis in rat brain with age and evidence that calorie
      restriction has the ability to attenuate this. Furthermore, our data suggest that
      calorie restriction provides neuroprotection through ARC by suppressing
      cytochrome c release and caspase-2 activity.

PMID- 12514108
TI  - Inhibition of tumor angiogenesis by cannabinoids.
AB  - Cannabinoids, the active components of marijuana and their derivatives, induce
      tumor regression in rodents (8). However, the mechanism of cannabinoid
      antitumoral action in vivo is as yet unknown. Here we show that local
      administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of
      malignant gliomas as determined by immunohistochemical analyses and vascular
      permeability assays. In vitro and in vivo experiments show that at least two
      mechanisms may be involved in this cannabinoid action: the direct inhibition of
      vascular endothelial cell migration and survival as well as the decrease of the
      expression of proangiogenic factors (vascular endothelial growth factor and
      angiopoietin-2) and matrix metalloproteinase-2 in the tumors. Inhibition of tumor
      angiogenesis may allow new strategies for the design of cannabinoid-based
      antitumoral therapies.

PMID- 12514109
TI  - Control of dendritic cell differentiation by angiotensin II.
AB  - Here we analyze the role of the angiotensinergic system in the differentiation of
      dendritic cells (DC). We found that human monocytes produce angiotensin II (AII)
      and express AT1 and AT2 receptors for AII. DC differentiated from human monocytes
      in the presence of AT1 receptor antagonists losartan or candesartan show very low
      levels of CD1a expression and poor endocytic and allostimulatory activities. By
      contrast, DC differentiation in the presence of either the AT2 receptor
      antagonist PD 123319 or exogenous AII results in the development of nonadherent
      cells with CD1a expression and endocytic and allostimulatory activities higher
      than control DC. Similar contrasting effects were observed in mouse DC obtained
      from bone marrow cultures supplemented with granulocyte-monocyte colony
      stimulating factor. DC differentiated in the presence of the AT1 receptor
      antagonist losartan express lower levels of CD11c, CD40, and Ia and display a
      lower ability to endocyte horseradish peroxidase (HRP) and to induce antibody
      responses in vivo, compared with controls. By contrast, DC differentiation in the
      presence of either the AT2 receptor antagonist PD 123319 or exogenous AII results
      in cells with high levels of CD11c, CD40, and Ia, as well as high ability to
      endocyte HRP and to induce antibody responses in vivo. Our results support the
      notion that the differentiation of DC is regulated by AII.

PMID- 12514110
TI  - High-efficiency growth hormone-releasing hormone plasmid vector administration
      into skeletal muscle mediated by electroporation in pigs.
AB  - We report here a very efficient method for the in vivo transfer of therapeutic
      plasmid DNA into porcine muscle fibers by using electric pulses of low field
      intensity. We evaluated delivery of 0.1-3 mg of plasmid vectors that encode
      reporter secreted-embryonic alkaline phosphatase (SEAP) or therapeutic growth
      hormone releasing hormone (GHRH). Reporter gene studies showed that internal
      needle electrodes give a 25-fold increase in expression levels compared with
      caliper electrodes in skeletal muscle in swine. Dose and time courses were
      performed. Pigs injected with 0.1 mg plasmid had significantly greater weight
      gain than controls over 53 days (22.4 +/- 0.8 kg vs. 19.7 +/- 0.03 kg,
      respectively; P<0.01). The group treated with GHRH-expressing plasmid at 14 days
      of age demonstrated greater weight gain than controls at every time point (25.8
      +/- 1.5 kg vs. 19.7 +/- 0.03 kg; P<0.01). Body composition studies by dual X-ray
      absorbitometry showed a 22% decrease in fat deposition (P<0.05) and a 10%
      increase in bone mineral density (P<0.004). Our studies demonstrate that by
      optimizing the electroporation method, favorable physiological changes, such as
      enhanced weight gain and improved body composition, can be obtained at extremely
      low plasmid doses in a large mammal.

PMID- 12514111
TI  - Regenerating lizard tails: a new model for investigating lymphangiogenesis.
AB  - Impaired lymphatic drainage in human limbs causes the debilitating swelling
      termed lymphoedema. In mammals, known growth factors involved in the control of
      lymphangiogenesis (growth of new lymph vessels) are vascular endothelial growth
      factors-C and -D (VEGF-C/D). Here we characterize a model of lymphangiogenesis in
      which the tail of lizards is regenerated without becoming oedematous. Three weeks
      after the tail is shed (autotomy), there are a small number of large diameter
      lymphatic vessels in the regenerated tail. Thereafter, the number increases and
      the diameter decreases. A functional lymphatic network, as determined by
      lymphoscintigraphy, is established 6 wk after autotomy. The new network differs
      morphologically and functionally from that in original tails. This lymphatic
      regeneration is associated with an up-regulation of a reptilian homologue of the
      VEGF-C/D protein family (rVEGF-C/D), as determined by Western blot analysis using
      a human reactive VEGF-C polyclonal antibody. Regenerating lizard tails are
      potentially useful models for studying the molecular basis of lymphangiogenesis
      with a view to developing possible treatments for human lymphoedema.

PMID- 12514112
TI  - Intravascular tissue factor initiates coagulation via circulating microvesicles
      and platelets.
AB  - Although tissue factor (TF), the principial initiator of physiological
      coagulation and pathological thrombosis, has recently been proposed to be present
      in human blood, the functional significance and location of the intravascular TF
      is unknown. In the plasma portion of blood, we found TF to be mainly associated
      with circulating microvesicles. By cell sorting with the specific marker CD42b,
      platelet-derived microvesicles were identified as a major location of the plasma
      TF. This was confirmed by the presence of full-length TF in microvesicles acutely
      shedded from the activated platelets. TF was observed to be stored in the alpha
      granules and the open canalicular system of resting platelets and to be exposed
      on the cell surface after platelet activation. Functional competence of the blood
      based TF was enabled when the microvesicles and platelets adhered to neutrophils,
      as mediated by P-selectin and neutrophil counterreceptor (PSGL-1, CD18 integrins)
      interactions. Moreover, neutrophil-secreted oxygen radical species supported the
      intravascular TF activity. The pools of platelet and microvesicle TF contributed
      additively and to a comparable extent to the overall blood TF activity,
      indicating a substantial participation of the microvesicle TF. Our results
      introduce a new concept of TF-mediated coagulation crucially dependent on TF
      associated with microvesicles and activated platelets, which principally enables
      the entire coagulation system to proceed on a restricted cell surface.

PMID- 12514113
TI  - Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine
      ligase gene expression.
AB  - Dietary use of curcumin, the active component of tumeric, one of the most widely
      used spices, is linked to several beneficial health effects, although the
      underlying molecular mechanisms remain largely unknown. Correlations have been
      established between curcumin exposure and increases in enzymes for glutathione
      synthesis, particularly glutamate-cysteine ligase (GCL), and metabolism as well
      as glutathione content, suggesting the eliciting of an adaptive response to
      stress. In this study, using HBE1 cells, we found that the mechanism of curcumin
      induced GCL elevation occurred via transcription of the two Gcl genes. Gcl
      transcription has been shown in several systems to be mediated through binding of
      transcription factor complexes to TRE and EpRE elements. Studies herein showed
      that curcumin caused modest but sustained increases in binding of proteins to DNA
      sequences for both cis elements but, more importantly, altered the compositions
      and nuclear content of proteins in these complexes. Curcumin exposure increased
      JunD and c-Jun content in AP-1 complexes and increased JunD while decreasing
      MafG/MafK in EpRE complexes. Thus, the beneficial effects elicited by curcumin
      appear to be due to changes in the pool of transcription factors that compose
      EpRE and AP-1 complexes, affecting gene expression of GCL and other phase II
      enzymes.

PMID- 12514114
TI  - Ferrocene-induced lymphocyte activation and anti-tumor activity is mediated by
      redox-sensitive signaling.
AB  - Ferrocene, a stable, synthetic, iron-containing compound induces in vitro and in
      vivo activation of mouse lymphocytes and macrophages. Ferrocene also has a marked
      antitumor effect in mice, upon its administration intraperitoneally and in
      drinking water. Ferrocene's antitumor activity is attributed to its immune
      stimulatory property. This conclusion is supported by adoptive transfer
      experiments demonstrating that immune cells from ferrocene-treated tumor-bearing
      mice elicit an antitumor effect in mice not treated with ferrocene. We postulate
      that the immune stimulatory effect of ferrocene is mediated by redox-sensitive
      signaling such as activation of p21ras. This postulation is supported by the
      following findings: Ferrocene generates H2O2 by autooxidation; N-acetylcysteine,
      a free-radical scavenger, reduces its antitumor effect; and it stimulates GTPase
      activity catalyzed by pure recombinant p21ras and activates ERK 1/2 in wild
      Jurkat T cells but fails to do so in the Jurkat T cells expressing p21ras in
      which cysteine 118 was replaced by serine. Lastly, ferrocene activates and
      translocates NF-kappaB in human PBM, a pathway which is mediated by ras. It is
      most plausible that additional redox-sensitive signaling proteins mediate the
      biological effects of ferrocene.

PMID- 12514115
TI  - Blockade of the apoptotic machinery by cyclosporin A redirects cell death toward
      necrosis in arterial endothelial cells: regulation by reactive oxygen species and
      cathepsin D.
AB  - Blockade of the mitochondrial permeability transition pore (mPTP) by cyclosporin
      A (CsA) inhibits apoptosis in various cell types. However, use of CsA in humans
      is associated with damage to the arterial endothelium. We evaluated whether
      inhibition of the apoptotic machinery by CsA promotes other forms of cell death
      in arterial endothelial cells (EC). Exposure of human umbilical artery EC (HUAEC)
      to clinically relevant concentrations of CsA for up to 24 h was associated with a
      significant increase in necrotic features. We detected inhibition of apoptosis
      and a significant increase in necrosis in HUAEC exposed concomitantly to CsA and
      mitomycin C, a proapoptotic DNA damaging agent. We found that CsA-induced cell
      death is independent of caspase activation, p53 induction, and calcineurin
      inhibition. However, bongkrekic acid, another mPTP blocker, also increased
      necrosis in HUAEC. Dihydroethidium and acridine orange staining revealed
      increased intracellular production of reactive oxygen species (ROS) followed by
      lysosomal damage in HUAEC exposed to CsA. Hydroxyl radical and superoxide
      scavengers and inhibition of cathepsin D activity significantly attenuated CsA
      induced EC death. These results suggest that inhibition of the apoptotic
      machinery by CsA in arterial EC favors development of a necrotic form of cell
      death regulated by ROS and secondary lysosomal damage.

PMID- 12514116
TI  - Cyclic strain inhibits switching of smooth muscle cells to an osteoblast-like
      phenotype.
AB  - Ectopic calcification is commonly associated with cardiovascular disease, injury,
      aging, and biomaterial implantation. We hypothesized that the normal mechanical
      environment of smooth muscle cells (SMCs) inhibits a phenotypic switch to a
      pattern of gene expression more typical for bone and inducive for calcification.
      This hypothesis was tested using a 3-D engineered smooth muscle tissue model
      subjected to cyclic mechanical strain. This simplified model maintained a 3-D
      tissue architecture while eliminating systemic effects as can be seen with in
      vivo models. All engineered tissues were found to express bone-associated genes
      (osteopontin, matrix gla protein, alkaline phosphatase, and the transcription
      factor CBFA-1). Strikingly, however, expression of these genes was down-regulated
      in tissues exposed to cyclic strain at all time points ranging from 5 to 150
      days. Furthermore, long-term strain played a protective role in regard to
      calcification, as unstrained tissues exhibited increased calcium deposition with
      respect to strained tissues. The results of this study suggest that without an
      appropriate mechanical environment, SMCs in 3-D culture undergo a phenotypic
      conversion to an osteoblast-like pattern of gene expression. This finding has
      significant implications for the mechanisms underlying a variety of
      cardiovascular diseases and indicates the broad utility of engineered tissue
      models in basic biology studies.

PMID- 12514117
TI  - CD38/cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth
      muscle hyper-responsiveness.
AB  - We previously demonstrated that cyclic ADP-ribose (cADPR) elicits Ca2+ release in
      airway smooth muscle (ASM) cells through ryanodine receptor channels. CD38 is a
      cell surface protein that catalyzes the synthesis and degradation of cADPR. In
      inflammatory diseases such as asthma, augmented Ca2+ responses and Ca2+
      sensitivity contribute to increased ASM contractility in response to agonists. In
      this study, we investigated the regulation of CD38 expression and the role of
      cADPR-mediated Ca2+ release in airway inflammation. Human ASM cells in culture
      between the second and fifth passages were exposed to tumor necrosis factor alpha
      (TNF-alpha), interleukin 1beta, or interferon gamma, or bovine serum albumin
      (controls). CD38 expression was measured by reverse transcriptase-polymerase
      chain reaction (RT-PCR), real-time PCR, and Western blot analysis, and ADP
      ribosyl cyclase activity was assayed with nicotinamide guanine dinucleotide as
      the substrate. Ca2+ responses to acetylcholine, bradykinin, and thrombin were
      measured in fura-2AM-loaded cells by fluorescence microscopy. Cytokines caused
      significant augmentation of CD38 expression, ADP-ribosyl cyclase activity, and
      Ca2+ responses to the agonists, compared with the control. TNF-alpha effects were
      greater than those of the other two cytokines. The cADPR antagonist 8-bromo-cADPR
      attenuated the Ca2+ responses to the agonists in control and cytokine-treated
      cells, with the magnitude of inhibition correlating with the level of CD38. This
      study provides the first demonstration of a role for CD38-cADPR signaling in a
      model of inflammatory airway disease.

PMID- 12514118
TI  - Angiopoietin-1-induced PI3-kinase activation prevents neuronal apoptosis.
AB  - Although angiopoietin-1 (Ang-1) is recognized as an endothelial growth factor,
      its presence in brain following an ischemic event suggests a role in the
      evolution of neuronal damage. Using primary neuronal cultures, we showed that
      neurons express Ang-1 and possess the functional angiopoietin-receptor Tie-2,
      which is phosphorylated in the presence of Ang-1. We further investigated in
      vitro whether Ang-1 could protect neurons against either excitotoxic necrosis or
      apoptosis induced by serum deprivation (SD). A neuroprotective effect for Ang-1
      was detected exclusively in the apoptotic paradigm. Treatment of cells with the
      phosphatidyl-inositol 3-kinase (PI3-K) inhibitor, LY294002, inhibited Ang-1
      induced phosphorylation of Akt, restored the cleavage of the effector caspase-3,
      and reduced the protective effect of Ang-1 against SD-induced toxicity. These
      findings suggest that Ang-1 has a neuroprotective effect against apoptotic stress
      and that this effect is dependent on the PI3-K/Akt pathway and inhibition of
      caspase-3 cleavage. This study provides evidence that Ang-1 is not just
      angiogenic but also neuroprotective. The understanding of neuroprotective
      mechanisms induced by Ang-1 may promote strategies based on the pleiotropic
      effects of angiogenic factors. Such approaches could be useful for the treatment
      of brain diseases in which both neuronal death and angiogenesis are involved.

PMID- 12514119
TI  - Regulation of the multidrug resistance transporter P-glycoprotein in
      multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive
      oxygen species.
AB  - Hypoxia in tumors is generally associated with chemoresistance and
      radioresistance. However, the correlation between the heterodimeric hypoxia
      inducible factor-1 (HIF-1) and the multidrug resistance transporter P
      glycoprotein (P-gp) has not been investigated. Herein, we demonstrate that with
      increasing size of DU-145 prostate multicellular tumor spheroids the pericellular
      oxygen pressure and the generation of reactive oxygen species decreased, whereas
      the alpha-subunit of HIF-1 (HIF-1alpha) and P-gp were up-regulated. Furthermore,
      P-gp was up-regulated under experimental physiological hypoxia and chemical
      hypoxia induced by either cobalt chloride or desferrioxamine. The pro-oxidants
      H2O2 and buthionine sulfoximine down-regulated HIF-1alpha and P-gp, whereas up
      regulation was achieved with the radical scavengers dehydroascorbate, N
      acetylcysteine, and vitamin E. The correlation of HIF-1alpha and P-gp expression
      was validated by the use of hepatoma tumor spheroids that were either wild type
      (Hepa1) or mutant (Hepa1C4) for aryl hydrocarbon receptor nuclear translocator
      (ARNT), i.e., HIF-1beta. Chemical hypoxia robustly increased HIF-1alpha as well
      as P-gp expression in Hepa1 tumor spheroids, whereas no changes were observed in
      Hepa1C4 spheroids. Hence, our data demonstrate that expression of P-gp in
      multicellular tumor spheroids is under the control of HIF-1.

PMID- 12514120
TI  - Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor
      signaling during vascular maturation.
AB  - RGS proteins finely tune heterotrimeric G-protein signaling. Implying the need
      for such fine-tuning in the developing vascular system, in situ hybridization
      revealed a striking and extensive expression pattern of Rgs5 in the arterial
      walls of E12.5-E17.5 mouse embryos. The distribution and location of the Rgs5
      positive cells typified that of pericytes and strikingly overlapped the known
      expression pattern of platelet-derived growth factor receptor (PDGFR)-beta. Both
      E14.5 PDGFR-beta- and platelet-derived growth factor (PDGF)-B-deficient mice
      exhibited markedly reduced levels of Rgs5 in their vascular plexa and small
      arteries. This likely reflects the loss of pericytes in the mutant mice. RGS5
      acts as a potent GTPase activating protein for Gi(alpha) and Gq(alpha) and it
      attenuated angiotensin II-, endothelin-1-, sphingosine-1-phosphate-, and PDGF
      induced ERK-2 phosphorylation. Together these results indicate that RGS5 exerts
      control over PDGFR-beta and GPCR-mediated signaling pathways active during fetal
      vascular maturation.

PMID- 12514121
TI  - Control of pelage hair follicle development and cycling by complex interactions
      between follistatin and activin.
AB  - Members of the transforming growth factor beta/bone morphogenetic protein (TGF
      beta/BMP) family are involved in the control of hair follicle (HF) morphogenesis
      and cycling. The activities of several members of this family activins and BMP-2,
      -4, -7, and -11) are controlled by antagonists such as follistatin. Because
      follistatin-deficient mice show abnormalities in vibrissae development, we
      explored the role of follistatin and activin in pelage HF development and
      cycling. We show here that during HF development follistatin mRNA was prominently
      expressed by hair matrix and outer root sheath keratinocytes as well as by
      interfollicular epidermal cells, whereas activin betaA mRNA was mainly expressed
      in dermal papilla cells. Compared with age-matched wild-type controls, both
      follistatin knockout mice and activin betaA transgenic mice showed a significant
      retardation of HF morphogenesis. Treatment of wild-type embryonic skin explants
      with follistatin protein stimulated HF development. This effect was inhibited by
      addition of recombinant activin A protein. Activin betaA transgenic mice
      demonstrated retardation of catagen entry, down-regulation of BMP-2, and up
      regulation of expression of its antagonist matrix GLA protein. These observations
      suggest that follistatin and activin interaction plays an important role in both
      HF development and cycling, possibly in part by regulating expression of BMP-2
      and its antagonist.

PMID- 12514122
TI  - Evidence for protein phosphatase inhibitor-1 playing an amplifier role in beta
      adrenergic signaling in cardiac myocytes.
AB  - The protein phosphatase inhibitor-1 (PPI-1) inhibits phosphatase type-1 (PP1)
      only when phosphorylated by protein kinase A and could play a pivotal role in the
      phosphorylation/dephosphorylation balance. Rat cardiac PPI-1 was cloned by
      reverse transcriptase-polymerase chain reaction, expressed in Eschericia coli,
      evaluated in phosphatase assays, and used to generate an antiserum. An adenovirus
      was constructed encoding PPI-1 and green fluorescent protein (GFP) under separate
      cytomegalovirus promotors (AdPPI-1/GFP). A GFP-only virus (AdGFP) served as
      control. Engineered heart tissue (EHT) from neonatal rat cardiomyocytes and adult
      rat cardiac myocytes (ARCMs) were used as model systems. PPI-1 expression was
      determined in human ventricular samples by Northern blots. Compared with AdGFP,
      AdPPI-1/GFP-infected neonatal rat cardiomyocytes displayed a 73% reduction in PP1
      activity. EHTs infected with AdPPI-1/GFP exhibited a fivefold increase in
      isoprenaline sensitivity. AdPPI-1/GFP-infected ARCMs displayed enhanced cell
      shortening as well as enhanced phospholamban phosphorylation when stimulated with
      1 nM isoprenaline. PPI-1 mRNA levels were reduced by 57+/-12% in failing hearts
      with dilated and ischemic cardiomyopathy (n=8 each) compared with nonfailing
      hearts (n=8). In summary, increased PPI-1 expression enhances myocyte sensitivity
      to isoprenaline, indicating that PPI-1 acts as an amplifier in beta-adrenergic
      signaling. Decreased PPI-1 in failing human hearts could participate in
      desensitization of the cAMP pathway.

PMID- 12514123
TI  - Termination of translation: interplay of mRNA, rRNAs and release factors?
AB  - Termination of translation in eukaryotes has focused recently on functional
      anatomy of polypeptide chain release factor, eRF1, by using a variety of
      different approaches. The tight correlation between the domain structure and
      different functions of eRF1 has been revealed. Independently, the role of
      prokaryotic RF1/2 in GTPase activity of RF3 has been deciphered, as well as RF3
      function itself.

PMID- 12514124
TI  - Structure of 23S rRNA hairpin 35 and its interaction with the tylosin-resistance
      methyltransferase RlmAII.
AB  - The bacterial rRNA methyltransferase RlmAII (formerly TlrB) contributes to
      resistance against tylosin-like 16-membered ring macrolide antibiotics. RlmAII
      was originally discovered in the tylosin-producer Streptomyces fradiae, and
      members of this subclass of methyltransferases have subsequently been found in
      other Gram-positive bacteria, including Streptococcus pneumoniae. In all cases,
      RlmAII methylates 23S rRNA at nucleotide G748, which is situated in a stem-loop
      (hairpin 35) at the macrolide binding site of the ribosome. The conformation of
      hairpin 35 recognized by RlmAII is shown here by NMR spectroscopy to resemble the
      anticodon loop of tRNA. The loop folds independently of the rest of the 23S rRNA,
      and is stabilized by a non-canonical G-A pair and a U-turn motif, rendering G748
      accessible. Binding of S.pneumoniae RlmAII induces changes in NMR signals at
      specific nucleotides that are involved in the methyltransferase-RNA interaction.
      The conformation of hairpin 35 that interacts with RlmAII is radically different
      from the structure this hairpin adopts within the 50S subunit. This indicates
      that the hairpin undergoes major structural rearrangement upon interaction with
      ribosomal proteins during 50S assembly.

PMID- 12514125
TI  - Domains of eIF1A that mediate binding to eIF2, eIF3 and eIF5B and promote ternary
      complex recruitment in vivo.
AB  - Translation initiation factor 1A (eIF1A) is predicted to bind in the decoding
      site of the 40S ribosome and has been implicated in recruitment of the eIF2-GTP
      Met-tRNA i Met ternary complex (TC) and ribosomal scanning. We show that the
      unstructured C-terminus of eIF1A interacts with the C-terminus of eIF5B, a factor
      that stimulates 40S-60S subunit joining, and removal of this domain of eIF1A
      diminishes translation initiation in vivo. These findings support the idea that
      eIF1A-eIF5B association is instrumental in releasing eIF1A from the ribosome
      after subunit joining. A larger C-terminal truncation that removes a 3(10) helix
      in eIF1A deregulates GCN4 translation in a manner suppressed by overexpressing
      TC, implicating eIF1A in TC binding to 40S ribosomes in vivo. The unstructured N
      terminus of eIF1A interacts with eIF2 and eIF3 and is required at low
      temperatures for a step following TC recruitment. We propose a modular
      organization for eIF1A wherein a core ribosome-binding domain is flanked by
      flexible segments that mediate interactions with other factors involved in
      recruitment of TC and release of eIF1A at subunit joining.

PMID- 12514126
TI  - The structure of ActVA-Orf6, a novel type of monooxygenase involved in
      actinorhodin biosynthesis.
AB  - ActVA-Orf6 monooxygenase from Streptomyces coelicolor that catalyses the
      oxidation of an aromatic intermediate of the actinorhodin biosynthetic pathway is
      a member of a class of small monooxygenases that carry out oxygenation without
      the assistance of any of the prosthetic groups, metal ions or cofactors normally
      associated with activation of molecular oxygen. The overall structure is a
      ferredoxin-like fold with a novel dimeric assembly, indicating that the widely
      represented ferredoxin fold may sustain yet another functionality. The resolution
      (1.3 A) of the enzyme structure and its complex with substrate and product
      analogues allows us to visualize the mechanism of binding and activation of the
      substrate for attack by molecular oxygen, and utilization of two gates for the
      reaction components including a proton gate and an O(2)/H(2)O gate with a
      putative protein channel. This is the first crystal structure of an enzyme
      involved in the tailoring of a type II aromatic polyketide and illustrates some
      of the enzyme-substrate recognition features that may apply to a range of other
      enzymes involved in modifying a polyketide core structure.

PMID- 12514127
TI  - Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel
      HCN2.
AB  - Hyperpolarization-activated cation (HCN) channels are believed to be involved in
      the generation of cardiac pacemaker depolarizations as well as in the control of
      neuronal excitability and plasticity. The contributions of the four individual
      HCN channel isoforms (HCN1-4) to these diverse functions are not known. Here we
      show that HCN2-deficient mice exhibit spontaneous absence seizures. The
      thalamocortical relay neurons of these mice displayed a near complete loss of the
      HCN current, resulting in a pronounced hyperpolarizing shift of the resting
      membrane potential, an altered response to depolarizing inputs and an increased
      susceptibility for oscillations. HCN2-null mice also displayed cardiac sinus
      dysrhythmia, a reduction of the sinoatrial HCN current and a shift of the maximum
      diastolic potential to hyperpolarized values. Mice with cardiomyocyte- specific
      deletion of HCN2 displayed the same dysrhythmia as mice lacking HCN2 globally,
      indicating that the dysrhythmia is indeed caused by sinoatrial dysfunction. Our
      results define the physiological role of the HCN2 subunit as a major determinant
      of membrane resting potential that is required for regular cardiac and neuronal
      rhythmicity.

PMID- 12514128
TI  - Trehalose synthesis and metabolism are required at different stages of plant
      infection by Magnaporthe grisea.
AB  - The relationship of trehalose metabolism to fungal virulence was explored in the
      rice blast fungus Magnaporthe grisea. To determine the role of trehalose
      synthesis in pathogenesis, we identified and deleted TPS1, encoding trehalose-6
      phosphate synthase. A Deltatps1 mutant failed to synthesize trehalose, sporulated
      poorly and was greatly attenuated in pathogenicity. Appressoria produced by
      Deltatps1 did not develop full turgor or elaborate penetration hyphae
      efficiently. To determine the role of subsequent trehalose breakdown, we deleted
      NTH1, which encodes a neutral trehalase. Nth1 mutants infected plants normally,
      but showed attenuated pathogenicity due to a decreased ability to colonize plant
      tissue. A second trehalase was also identified, required both for growth on
      trehalose and mobilization of intracellular trehalose during infection-related
      development. TRE1 encodes a cell wall-localized enzyme with characteristics of
      both neutral and acidic trehalases, but is dispensable for pathogenicity. Our
      results indicate that trehalose synthesis, but not its subsequent breakdown, is
      required for primary plant infection by M.grisea, while trehalose degradation is
      important for efficient development of the fungus in plant tissue following
      initial infection.

PMID- 12514129
TI  - Heparan sulfate chains of perlecan are indispensable in the lens capsule but not
      in the kidney.
AB  - Mice lacking exon 3 of perlecan (Hspg2) gene were generated by gene targeting.
      Exon deletion does not alter the expression or the reading frame but causes loss
      of attachment sites for three heparan sulfate (HS) side chains. Hspg2(Delta 3 /
      Delta 3) mice are viable and fertile but have small eyes. Apoptosis and leakage
      of cellular material through the lens capsule are observed in neonatal lenses,
      and lenses degenerate within 3 weeks of birth. Electron microscopy revealed
      altered structure of the lens capsule through which cells had formed extensions.
      No kidney malfunction, such as protein uria, was detected in Hspg2(Delta 3 /
      Delta 3) mutant mice, nor were ultrastructural changes observed in the glomerular
      basement membranes (BMs). To achieve further depletion in the HS content of the
      BMs, Hspg2(Delta 3 / Delta 3) mice were bred with collagen XVIII null mice. Lens
      defects were more severe in the newborn Col18a1(-/-) x Hspg2(Delta 3 / Delta 3)
      mice and degeneration proceeded faster than in Hspg2(Delta 3 / Delta 3) mice. The
      results suggest that in the lens capsule, HS chains have a structural function
      and are essential in the insulation of the lens from its environment and in
      regulation of incoming signals.

PMID- 12514130
TI  - Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis.
AB  - Plasmid R1 inhibits growth of bacteria by synthesizing an inhibitor of cell
      proliferation, Kid, and a neutralizing antidote, Kis, which binds tightly to the
      toxin. Here we report that this toxin and antidote, which have evolved to
      function in bacteria, also function efficiently in a wide range of eukaryotes.
      Kid inhibits cell proliferation in yeast, Xenopus laevis and human cells, whilst
      Kis protects. Moreover, we show that Kid triggers apoptosis in human cells. These
      effects can be regulated in vivo by modulating the relative amounts of antidote
      and toxin using inducible eukaryotic promoters for independent transcriptional
      control of their genes. These findings allow highly regulatable, selective
      killing of eukaryotic cells, and could be applied to eliminate cancer cells or
      specific cell lineages in development.

PMID- 12514131
TI  - POSH acts as a scaffold for a multiprotein complex that mediates JNK activation
      in apoptosis.
AB  - We report that the multidomain protein POSH (plenty of SH3s) acts as a scaffold
      for the JNK pathway of neuronal death. This pathway consists of a sequential
      cascade involving activated Rac1/Cdc42, mixed-lineage kinases (MLKs), MAP kinase
      kinases (MKKs) 4 and 7, c-Jun N-terminal kinases (JNKs) and c-Jun, and is
      required for neuronal death induced by various means including nerve growth
      factor (NGF) deprivation. In addition to binding GTP-Rac1 as described
      previously, we find that POSH binds MLKs both in vivo and in vitro, and complexes
      with MKKs 4 and 7 and with JNKs. POSH overexpression promotes apoptotic neuronal
      death and this is suppressed by dominant-negative forms of MLKs, MKK4/7 and c
      Jun, and by an MLK inhibitor. Moreover, a POSH antisense oligonucleotide and a
      POSH small interfering RNA (siRNA) suppress c-Jun phosphorylation and neuronal
      apoptosis induced by NGF withdrawal. Thus, POSH appears to function as a scaffold
      in a multiprotein complex that links activated Rac1 and downstream elements of
      the JNK apoptotic cascade.

PMID- 12514132
TI  - Retinoids regulate the anterior expression boundaries of 5' Hoxb genes in
      posterior hindbrain.
AB  - We describe the regulatory interactions that cause anterior extension of the
      mouse 5' Hoxb expression domains from spinal cord levels to their definitive
      boundaries in the posterior hindbrain between embryonic day E10 and E11.5. This
      anterior expansion is retinoid dependent since it does not occur in mouse embryos
      deficient for the retinoic acid-synthesizing enzyme retinaldehyde dehydrogenase
      2. A retinoic acid response element (RARE) was identified downstream of Hoxb5 and
      shown to be essential for expression of Hoxb5 and Hoxb8 reporter transgenes in
      the anterior neural tube. The spatio-temporal activity of this element overlaps
      with rostral extension of the expression domain of endogenous Hoxb5, Hoxb6 and
      Hoxb8 into the posterior hindbrain. The RARE and surrounding sequences are found
      at homologous positions in the human, mouse and zebrafish genome, which supports
      an evolutionarily conserved regulatory function.

PMID- 12514133
TI  - A novel inducible transactivation domain in the androgen receptor: implications
      for PRK in prostate cancer.
AB  - In addition to the classical activation by ligands, nuclear receptor activity is
      also regulated by ligand-independent signalling. Here, we unravel a novel signal
      transduction pathway that links the RhoA effector protein kinase C-related kinase
      PRK1 to the transcriptional activation of the androgen receptor (AR). Stimulation
      of the PRK signalling cascade results in a ligand-dependent superactivation of
      AR. We show that AR and PRK1 interact both in vivo and in vitro. The
      transactivation unit 5 (TAU-5) located in the N-terminus of AR suffices for
      activation by PRK1. Thus, TAU-5 defines a novel, signal-inducible transactivation
      domain. Furthermore, PRK1 promotes a functional complex of AR with the co
      activator TIF-2. Importantly, PRK signalling also stimulates AR activity in the
      presence of adrenal androgens, which are still present in prostate tumour
      patients subjected to testicular androgen ablation therapy. Moreover, PRK1
      activates AR even in the presence of the AR antagonist cyproterone acetate that
      is used in the clinical management of prostate cancer. Since prostate tumours
      strongly overexpress PRK1, our data support a model in which AR activity is
      controlled by PRK signalling.

PMID- 12514134
TI  - MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of
      the co-activator p300.
AB  - CBP/p300 recruitment to enhancer-bound complexes is a key determinant in promoter
      activation by many transcription factors. We present a novel mechanism of
      activating such complexes and show that pre-assembled Elk-1-p300 complexes become
      activated following Elk-1 phosphorylation by changes in Elk-1-p300 interactions
      rather than recruitment. It is known that Elk-1 binds to promoter in the absence
      of stimuli. However, it is unclear how activation of Elk-1 by mitogen-acivated
      protein kinase (MAPK)-mediated phosphorylation leads to targeted gene
      transactivation. We show that Elk-1 can interact with p300 in vitro and in vivo
      in the absence of a stimulus through the Elk-1 C-terminus and the p300 N
      terminus. Phosphorylation on Ser383 and Ser389 of Elk-1 by MAPK enhances this
      basal binding but, most importantly, Elk-1 exhibits new interactions with p300.
      These interaction changes render a strong histone acetyltransferase activity in
      the Elk-1-associated complex that could play a critical role in chromatin
      remodeling and gene activation. The pre-assembly mechanism may greatly accelerate
      transcription activation, which is important in regulation of expression of
      immediate-early response genes, in particular those involved in stress responses.

PMID- 12514135
TI  - Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9
      AdoMet.
AB  - The methylation of lysine residues of histones plays a pivotal role in the
      regulation of chromatin structure and gene expression. Here, we report two
      crystal structures of SET7/9, a histone methyltransferase (HMTase) that transfers
      methyl groups to Lys4 of histone H3, in complex with S-adenosyl-L-methionine
      (AdoMet) determined at 1.7 and 2.3 A resolution. The structures reveal an active
      site consisting of: (i) a binding pocket between the SET domain and a c-SET helix
      where an AdoMet molecule in an unusual conformation binds; (ii) a narrow
      substrate-specific channel that only unmethylated lysine residues can access; and
      (iii) a catalytic tyrosine residue. The methyl group of AdoMet is directed to the
      narrow channel where a substrate lysine enters from the opposite side. We
      demonstrate that SET7/9 can transfer two but not three methyl groups to
      unmodified Lys4 of H3 without substrate dissociation. The unusual features of the
      SET domain-containing HMTase discriminate between the un- and methylated lysine
      substrate, and the methylation sites for the histone H3 tail.

PMID- 12514136
TI  - Determinants in mammalian telomerase RNA that mediate enzyme processivity and
      cross-species incompatibility.
AB  - Telomerase contains two essential components: an RNA molecule that templates
      telomeric repeat synthesis and a catalytic protein component. Human telomerase is
      processive, while the mouse enzyme has much lower processivity. We have
      identified nucleotide determinants in the telomerase RNA that are responsible for
      this difference in processivity. Mutations adjacent to the template region of
      human and mouse telomerase RNA significantly altered telomerase processivity both
      in vitro and in vivo. We also identified functionally important nucleotides in
      the pseudoknot domain of telomerase RNA that potentially mediate the
      incompatibility between human TERT and mouse telomerase RNA. These experiments
      identify essential residues of the telomerase RNA that regulate telomerase
      activity and processivity.

PMID- 12514137
TI  - Excess SeqA prolongs sequestration of oriC and delays nucleoid segregation and
      cell division.
AB  - Following initiation of chromosomal replication in Escherichia coli, newly
      initiated origins (oriCs) are prevented from further initiations by a mechanism
      termed sequestration. During the sequestration period (which lasts about one
      third of a cell cycle), the origins remain hemimethylated. The SeqA protein binds
      hemimethylated oriC in vitro. In vivo, the absence of SeqA causes overinitiation
      and strongly reduces the duration of hemimethylation. The pattern of
      immunostained SeqA complexes in vivo suggests that SeqA has a role in organizing
      hemimethylated DNA at the replication forks. We have examined the effects of
      overexpressing SeqA under different cellular conditions. Our data demonstrate
      that excess SeqA significantly increases the time oriC is hemimethylated
      following initiation of replication. In some cells, sequestration continued for
      more than one generation and resulted in inhibition of primary initiation. SeqA
      overproduction also interfered with the segregation of sister nucleoids and
      caused a delay in cell division. These results suggest that SeqA's function in
      regulation of replication initiation is linked to chromosome segregation and
      possibly cell division.

PMID- 12514138
TI  - Hallmarks of homology recognition by RecA-like recombinases are exhibited by the
      unrelated Escherichia coli RecT protein.
AB  - Homologous recombination is a fundamental process for genome maintenance and
      evolution. Various proteins capable of performing homology recognition and
      pairing of DNA strands have been isolated from many organisms. The RecA family of
      proteins exhibits a number of biochemical properties that are considered
      hallmarks of homology recognition. Here, we investigated whether the unrelated
      Escherichia coli RecT protein, which mediates homologous pairing and strand
      exchange, also exhibits such properties. We found that, like RecA and known RecA
      homologs: (i) RecT promotes the co-aggregation of ssDNA with duplex DNA, which is
      known to facilitate homologous contacts; (ii) RecT binding to ssDNA mediates
      unstacking of the bases, a key step in homology recognition; (iii) RecT mediates
      the formation of a three-strand synaptic intermediate where pairing is
      facilitated by local helix destabilization, and the preferential switching of A:T
      base pairs mediates recognition of homology; and (iv) RecT-mediated pairing
      occurs from both 3'- and 5'-single-stranded ends. Taken together, our results
      show that RecT shares fundamental homology-recognition properties with the RecA
      homologs, and provide new insights on an underlying universal mechanism of
      homologous recognition.

PMID- 12514139
TI  - Arabidopsis TOBAMOVIRUS MULTIPLICATION (TOM) 2 locus encodes a transmembrane
      protein that interacts with TOM1.
AB  - The tom2-1 mutation of Arabidopsis thaliana reduces the efficiency of
      intracellular multiplication of tobamoviruses. The tom2-1 mutant was derived from
      fast-neutron-irradiated seeds, and the original mutant line also carries ttm1, a
      dominant modifier that increases tobamovirus multiplication efficiency in a
      tobamovirus-strain-specific manner in the tom2-1 genetic background. Here, we
      show that the tom2-1 mutation involved a deletion of approximately 20 kb in the
      nuclear genome. The deleted region included two genes named TOM2A and TOM2B that
      were both associated with the tom2-1 phenotype, whereas ttm1 corresponded to the
      translocation of part of the deleted region that included intact TOM2B but not
      TOM2A. TOM2A encodes a 280 amino acid putative four-pass transmembrane protein
      with a C-terminal farnesylation signal, while TOM2B encodes a 122 amino acid
      basic protein. The split-ubiquitin assay demonstrated an interaction of TOM2A
      both with itself and with TOM1, an integral membrane protein of A.thaliana
      presumed to be an essential constituent of tobamovirus replication complex. The
      data presented here suggest that TOM2A is also an integral part of the
      tobamovirus replication complex.

PMID- 12514140
TI  - Subcellular localization of host and viral proteins associated with tobamovirus
      RNA replication.
AB  - Arabidopsis TOM1 (AtTOM1) and TOM2A (AtTOM2A) are integral membrane proteins
      genetically identified to be necessary for efficient intracellular multiplication
      of tobamoviruses. AtTOM1 interacts with the helicase domain polypeptide of
      tobamovirus-encoded replication proteins and with AtTOM2A, suggesting that both
      AtTOM1 and AtTOM2A are integral components of the tobamovirus replication
      complex. We show here that AtTOM1 and AtTOM2A proteins tagged with green
      fluorescent protein (GFP) are targeted to the vacuolar membrane (tonoplast)-like
      structures in plant cells. In subcellular fractionation analyses, GFP-AtTOM2A,
      AtTOM2A and its tobacco homolog NtTOM2A were predominantly fractionated to low
      density tonoplast-rich fractions, whereas AtTOM1-GFP, AtTOM1 and its tobacco
      homolog NtTOM1 were distributed mainly into the tonoplast-rich fractions and
      partially into higher-buoyant-density fractions containing membranes from several
      other organelles. The tobamovirus-encoded replication proteins were co
      fractionated with both NtTOM1 and viral RNA-dependent RNA polymerase activity.
      The replication proteins were also found in the fractions containing non-membrane
      bound proteins, but neither NtTOM1 nor the polymerase activity was detected
      there. These observations suggest that the formation of tobamoviral RNA
      replication complex occurs on TOM1-containing membranes and is facilitated by
      TOM2A.

PMID- 12514141
TI  - Opioid therapy and chronic non-cancer pain/Le traitement aux opioides et la
      douleur non cancereuse.

PMID- 12514142
TI  - The LMA, laparoscopic surgery and the obese patient - can vs should: Le ML, la
      chirurgie laparoscopique et le patient obese - pouvoir vs devoir.

PMID- 12514143
TI  - Best evidence in anesthetic practice: prevention: dimenhydrinate prevents
      postoperative nausea and vomiting.

PMID- 12514144
TI  - Desmopressin does not decrease blood loss and transfusion requirements in
      patients undergoing hepatectomy.
AB  - PURPOSE: To determine the effects of desmopressin on coagulation and blood loss
      in patients undergoing elective partial hepatectomy. METHODS: A randomized,
      controlled and double-blind study on 59 patients who received either 0.3 micro g
      x kg(-1) of desmopressin or an equal volume of normal saline (control) infused
      intravenously over 20 min after induction of general anesthesia. RESULTS: There
      was an increase in plasma levels of factors VIII and von Willebrand after the
      infusion of study drug in both groups (P < 0.001). The activated partial
      thromboplastin time was shortened in Group D whereas prothrombin time was
      prolonged in Group C; (P = 0.02). A large range of intraoperative blood loss (400
      7128 mL) was observed, with no significant differences between groups. There were
      no changes in plasma electrolyte levels or osmolality. Transfusion requirements
      were similar in both groups. CONCLUSION: Desmopressin did not reduce
      intraoperative blood loss or transfusion requirements during hepatectomy despite
      raising clotting factor levels and improving tests of hemostasis.

PMID- 12514145
TI  - Herbal medicine use is frequent in ambulatory surgery patients in Vancouver
      Canada.
AB  - PURPOSE: To determine the incidence and nature of herbal medicine use among
      patients in a busy Canadian surgical day care unit. METHODS: We undertook a
      prospective survey of 575 patients attending our surgical day care unit. The
      questionnaire inquired as to basic demographics, herbal medicine use, the name
      and number of herbal medicines used, reason, whether it was self prescribed or
      not, and if the patient's family physician was aware of the use. In the second
      part of the study, 44 anesthesiologists were asked to answer a questionnaire of
      27 yes/no questions to determine their knowledge of herbal medicines. RESULTS:
      Four hundred eighty-five of 575 patients completed the questionnaire (84%).
      Thirty-four percent of patients surveyed in our unit responded affirmatively to
      herbal medicine use. Of these, 39% took them on a daily basis. Forty-five
      different identifiable herbs were being taken in total, with echinacea being the
      most common. Less than half of the patients told their family physicians that
      they were using herbal medicines and only one-third of patients were taking them
      on the advice of their physician. In the assessment of anesthesiologists'
      knowledge of herbal medicine, only 32% of the questions were answered correctly.
      CONCLUSION: The incidence of herbal medicine ingestion by patients coming to our
      unit was higher than previously reported. A large variety of preparations were
      being taken, many without the knowledge of the patient's family physician. The
      basic knowledge of anesthesiologists with respect to herbal medicine is limited.

PMID- 12514146
TI  - A sevoflurane induction of anesthesia with gradual reduction of concentration is
      well tolerated in elderly patients.
AB  - PURPOSE: To establish the appropriate inhalation induction technique using a high
      concentration of sevoflurane in the elderly. METHODS: Forty-five patients, aged
      70-79-yr-old, were randomly divided into three groups: 1) Group I: anesthesia was
      induced with propofol 2 mg x kg(-1) and sevoflurane 2% (n = 15); 2) Group II:
      anesthesia was induced with a three- minute inhalation of sevoflurane 8%; 3)
      Group III: anesthesia was induced with inhalation of sevoflurane using a gradual
      reduction technique (8, 6, 4% for each minute). In Groups II and III, a modified
      vital capacity inhalation induction was performed. Mean arterial pressure (MAP),
      heart rate (HR) and oxygen saturation (SpO(2)) were measured continuously during
      induction. In addition, induction time and adverse events related to anesthetic
      induction were recorded. RESULTS: The induction time in Group I was significantly
      shorter than that in Groups II and III (P < 0.05). However, there was no
      difference in the induction time between Groups II and III. In Groups II and III,
      the majority of patients required additional breaths. In comparison with the
      other groups, stability of MAP was maintained in Group III. The variations of HR
      in all groups were small. During induction, no patient experienced a decrease in
      SpO(2) below 96%, except for two patients in Group I. Severe respiratory adverse
      events were not observed. Other adverse events were similar in all groups.
      CONCLUSIONS: Our results suggest that a high concentration sevoflurane induction
      using a gradual reduction technique may be an acceptable alternative to standard
      iv induction in elderly patients.

PMID- 12514147
TI  - Fentanyl-induced rigidity during emergence from general anesthesia potentiated by
      venlafexine.
AB  - PURPOSE: To present and discuss a case of opioid-induced rigidity with low-dose
      fentanyl during recovery from anesthesia. CLINICAL FEATURES: A 41-yr-old woman
      underwent laparotomy for total abdominal hysterectomy and bilateral salpingo-
      oophorectomy under general anesthesia. She received a total of 500 micro g of
      fentanyl by iv intermittent boluses during the three-hour anesthetic. During
      emergence from anesthesia, while intubated, the patient presented with rigidity.
      No changes in ventilatory parameters were measured during the episode. The only
      notable predisposing factor was treatment with venlafexine, an antidepressant
      that modifies serotonin and norepinephrine levels. She was successfully treated
      with iv naloxone 20 micro g. The rest of the postoperative period was uneventful.
      CONCLUSION: We observed an atypical case of opioid-induced rigidity in contrast
      to the classical syndrome, which presents at induction with high-dose opioids.
      This syndrome has many clinical presentations with neurologic and ventilatory
      signs of varying intensity. Early recognition of the syndrome and adequate
      treatment is crucial. If treated adequately, opioid-induced rigidity is self
      limited with few complications.

PMID- 12514148
TI  - Successful use of iv diltiazem to control perioperative refractory complex atrial
      tachyarrhythmias in a patient with pneumoconiosis.
AB  - PURPOSE: To present a patient with pneumoconiosis who developed a complex, life
      threatening atrial tachyarrhythmia during anesthesia. Intravenous diltiazem was
      effective in controlling the ventricular rate and hemodynamics after failure of
      other antiarrhythmic drugs and direct current cardioversion. CLINICAL FEATURES: A
      79-yr-old man with pneumoconiosis complicated by cor pulmonale suffered from gout
      related cellulitis of the left lower limb. Debridement of the left gangrenous big
      toe was carried out under general anesthesia. During anesthesia, a wide-QRS
      tachycardia occurred suddenly and a complex atrial tachyarrhythmia was later
      diagnosed. Hemodynamics deteriorated despite aggressive treatment with lidocaine,
      verapamil, direct current cardioversion, magnesium, digoxin and amiodarone.
      Correction of the underlying respiratory acidosis was not sufficient to control
      the rapid ventricular response. Eventually, iv diltiazem adequately controlled
      the rapid ventricular rate and quickly improved the deteriorating hemodynamics.
      CONCLUSION: Life-threatening complex atrial tachyarrhythmias may occur in
      patients with chronic lung diseases perioperatively. Intravenous diltiazem was
      effective in the management of complex atrial tachyarrhythmia in a patient with
      underlying cor pulmonale.

PMID- 12514149
TI  - Trends in opioid use for chronic neuropathic pain: a survey of patients pursuing
      enrollment in clinical trials.
AB  - PURPOSE: Clinical trials suggest that opioids relieve neuropathic pain and
      decrease pain-related disability. We conducted a pilot study of current
      prescribing trends and patients' attitudes towards opioids for neuropathic pain.
      METHODS: A patient questionnaire was completed by individuals pursuing enrollment
      in neuropathic pain clinical trials at our facility. RESULTS: Of 154 patients
      with diabetic neuropathy (55.2%), postherpetic neuralgia (29.9%), idiopathic
      peripheral neuropathy (9.7%) and other neuropathies (5.2%), 73.4% complained of
      inadequate pain control, the mean pain duration was 4.7 (SD = 4.4) yr and the
      mean pain intensity (0-10) was 7.7 (SD = 2.3). In this group, 40.9% had never
      tried opioids and 24.7% had never tried any opioids, tricyclic antidepressants or
      anticonvulsants. Only 9.7% were receiving long-acting opioids or "around the
      clock" dosing whereas 25.3% were receiving opioids on an "as needed" basis.
      Opioids combined with tricyclic antidepressants and/or anticonvulsants were used
      in 11.0%. Fear of addiction and adverse effects were expressed by 31.8% and 46.8%
      respectively. CONCLUSION: These data suggest that barriers to opioid therapy for
      neuropathic pain include patients', and possibly physicians', fears of addiction
      and adverse effects, which are exaggerated in light of current evidence. The
      merits of continuous treatment with sustained-release opioids, "as needed" dosing
      with short-acting preparations, or combining opioids with other agents are
      discussed. Continued research and communication between health professionals, law
      enforcement officials and legislators is vital in order to facilitate appropriate
      opioid use which has a minimal negative impact on the public yet optimally
      benefits individuals who suffer from disabling neuropathic pain.

PMID- 12514150
TI  - Tramadol 2.5 mg x kg(-1) appears to be the optimal intraoperative loading dose
      before patient-controlled analgesia.
AB  - PURPOSE: We previously established that a 5 mg x kg(-1) intraoperative dose can
      reduce the nausea/vomiting associated with tramadol patient-controlled analgesia
      (PCA). This study was conducted to identify the most appropriate initial dose to
      improve the quality of tramadol PCA. METHODS: During general anesthesia, 60
      patients undergoing knee arthroplasty were randomly allocated to receive 1.25 mg
      x kg(-1) (Group I), 2.5 mg x kg(-1) (Group II), 3.75 mg x kg(-1) (Group III), or
      5 mg x kg(-1) (Group IV) tramadol. The emergence condition was recorded. The
      titration of additional tramadol 20 mg + metoclopramide 1 mg doses by PCA every
      five minutes was performed in the postanesthesia care unit (PACU) until the
      visual analogue scale (VAS) score was < or = 3. An investigator blinded to study
      group recorded the VAS and side effects every ten minutes. RESULTS: In the PACU,
      significantly more tramadol (8.4 +/- 3.1 vs 4.3 +/- 2.1, 2.5 +/- 1.8, and 0.4 +/-
      0.3, P < 0.05), and a higher incidence (15/15 vs 5/15, 3/15, and 2/15, P < 0.05)
      of PCA use was observed in Group I compared to Groups II-IV. VAS was
      significantly higher in Group I than in Groups II-IV at zero and ten minutes (P <
      0.05). Unexpected delayed emergence anesthesia (> 30 min) was observed in Group
      III (n = 1) and in Group IV (n = 2). Sedation was more important in Groups III
      and IV than in Groups I and II (P < 0.05). CONCLUSION: When considering efficacy
      and side-effect profile, 2.5 mg x kg(-1) of tramadol is the optimal
      intraoperative dose of this drug to provide effective postoperative analgesia
      with minimal sedation.

PMID- 12514151
TI  - Sciatic nerve blockade in the supine position: a novel approach.
AB  - PURPOSE: Sciatic nerve block is useful for surgery below the knee both intra- and
      postoperatively. Several techniques to insert a catheter at the knee level or
      higher have been described but need mobilization (lateral decubitus) of the
      patient. We describe novel landmarks, using a high lateral approach, to block the
      sciatic nerve without moving the patient. CLINICAL FEATURES: One hundred seven
      ASA I, II and III ASA patients scheduled for major foot or ankle surgery were
      studied prospectively. With patients awake and lying in the supine position, the
      catheter was introduced along novel landmarks in the peri-nervous adipose space
      using specifically designed material and nerve stimulation (< 0.5 mA). After a
      negative test dose (1% lidocaine with 1/200.000 epinephrine), 10 mL of 0.5%
      bupivacaine and 10 mL of 2% lidocaine were injected. Thirty minutes after
      performance of the block, the cutaneous and dermatomal sensory blockade were
      assessed using cold and pinprick tests while motor block was assessed using a
      modified Bromage scale. Complications and incidents were recorded. The tibial and
      superficial peroneal nerve were always blocked, while the deep peroneal and
      postero-femoral cutaneous nerves were blocked in only 97% and 83% of the
      patients, respectively. Anesthesia, was always present in the dermatome L5 and in
      the S1 dermatome in 98% of the patients. No major incidents or complications were
      noted. Three catheters could not be inserted and the anesthestic solution was
      injected through the needle. CONCLUSION: The lateral technique for sciatic nerve
      anesthesia and catheter insertion allows patients to remain in the supine
      position for performance of the block and catheter insertion, and results in a
      high rate of homogeneous anesthesia and a low incidence of side effects.

PMID- 12514152
TI  - Continuous interscalene brachial plexus blockade provides good analgesia at home
      after major shoulder surgery-report of four cases.
AB  - PURPOSE: Continuous interscalene brachial plexus blockade (CIBPB) in a hospital
      setting can provide excellent surgical conditions and postoperative analgesia for
      major shoulder surgery. This is a case report of four patients on the efficacy
      and advantages of CIBPB for postoperative analgesia at home. CASE REPORTS: Four
      patients scheduled for rotator cuff repair under CIBPB were discharged home the
      day of surgery with an interscalene catheter connected to an automated infusion
      pump administering 0.2% ropivacaine at 10 mL x hr(-1) for 72 hr. Prior to
      discharge, patients and their attendant were given verbal and written
      instructions concerning local anesthetic toxicity and explicit contact
      information for an anesthesiologist or nurse. Outcomes were measured pre- and
      postoperatively, including verbal analogue pain scores (pain VAS), verbal
      analogue nausea scores (nausea VAS), side effects, cognitive function (mini
      mental state questionnaire), sleep (hours/night), and patient satisfaction
      (Likert scale). Postoperative VAS scores over three days were very low. Two
      patients reported only one episode of nausea. There were no complications
      associated with local anesthetic toxicity or catheter use. Cognitive function
      improved over three days. Sleep increased from a mean of five hours before
      surgery to seven hours over the next three nights. Patient satisfaction with care
      was high. Significant cost savings were documented. CONCLUSION: The use of CIBPB
      for 72 hr in patients undergoing major ambulatory shoulder surgery can result in
      good analgesia with minimal opioid requirement, cost savings and possibly
      improvement in outcome measures.

PMID- 12514153
TI  - Successful resuscitation of serious bupivacaine intoxication in a patient with
      pre-existing heart failure.
AB  - PURPOSE: In dogs intoxicated with bupivacaine, clonidine is effective to treat
      conduction disturbances and dobutamine corrects myocardial depression. We report
      the case of a patient who experienced severe bupivacaine cardiotoxicity and who
      was treated successfully using these medications. CLINICAL FEATURES: In a patient
      with pre-existing heart failure a surgical procedure to fix a humeral fracture
      was necessary. Preoperatively, heart failure was controlled with transcutaneous
      nitroglycerin and iv deslanoside. A bupivacaine bolus was administered iv
      accidentally (a mixture of bupivacaine 75 mg, 15 micro g clonidine). The patient
      developed nodal rhythm with extreme bradycardia, severe shock and convulsions.
      Seizures were controlled with thiopentone/succinylcholine. Epinephrine iv boluses
      (0.1 mg x 3) restored blood pressure (BP) to 50/30 mmHg and heart rate (HR) to 60
      (nodal rhythm). Following 75 micro g clonidine iv, BP rose to 90/70 and HR to 90
      min. Cardiac rhythm reverted to sinus rhythm with first degree atrio-ventricular
      block. Echocardiography showed hyperkinesia and relative hypovolemia that was
      controlled with iv administration of terlipressin and glucagon. Subsequent
      dobutamine infusion stabilized hemodynamic conditions. It was decided to proceed
      with surgery using a midazolam/sufentanil based general anesthetic. In the
      intensive care unit, recovery, extubation and weaning from the dobutamine
      infusion were realized within 16 hr of the event. CONCLUSIONS: In this patient
      with preoperative heart failure, clonidine was effective to treat bupivacaine
      induced conduction disturbances. Epinephrine and dobutamine were effective to
      treat myocardial depression and terlipressin effectively controlled
      vasodilatation.

PMID- 12514154
TI  - The effect of isoflurane 0.6% on respiratory mechanics in anesthetized-paralyzed
      humans is not increased at concentrations of 0.9% and 1.2%.
AB  - PURPOSE: To assess the dose-dependent effect of low concentrations of isoflurane
      on respiratory mechanics in normal subjects. METHODS: We studied 12 non
      premedicated ASA I patients scheduled for lower abdominal or extremity surgery.
      After thiopental 5-7 mg*kg(-1) iv and succinylcholine 1 mg x kg(-1) iv, the
      trachea was intubated and an esophageal balloon was placed optimally by the
      occlusion test. After introduction of N(2)O and muscle paralysis with vecuronium,
      we studied 0, 0.6, 0.9 and 1.2% isoflurane. We recorded flow (F), airway opening
      and esophageal pressures. Signals were amplified, filtered, sampled at 100 Hz,
      and then fed in a 12-bit analogue-digital converter in a personal computer. Data
      were collected and analyzed using LABDAT and ANADAT software. Signals were
      acquired for 60-90 sec during mechanical ventilation (10 mL x kg(-1), 10 breaths
      x min(-1), I:E ratio 1:2). We estimated respiratory system (RS), lung (L) and
      chest wall (W) dynamic elastance (E) and resistance (R) by P(t) = EV(T)(t) +
      RF(t) + K, where t is time, V(T) tidal volume from integration of F, and K an
      estimation of end-expiratory pressure. ANOVA was used for comparing the basal
      state with the three concentrations. RESULTS: E and R were statistically lower at
      0.6, 0.9 and 1.2% compared to basal values for RS, L and W. Concentrations equal
      to or higher than 0.6% did not further change respiratory mechanics, except for
      E(L1.2) compared to E(L0.6,) 12.37 +/- 5.72 and 13.52 +/- 5.64 cm H(2)O.L(-1),
      respectively. CONCLUSION: Isoflurane concentrations between 0.6-1.2% are not
      associated to a dose-dependent effect on respiratory mechanics.

PMID- 12514155
TI  - LMA-Classic and LMA-ProSeal are effective alternatives to endotracheal intubation
      for gynecologic laparoscopy.
AB  - PURPOSE: To compare the laryngeal mask airways (LMA), LMA-Classic(TM) (LMA-C) and
      LMA-ProSeal(TM) (PLMA) with the endotracheal tube (ETT) with respect to pulmonary
      ventilation and gastric distension during gynecologic laparoscopy. METHODS: We
      stratified 209 women, aged > or = 18 yr, ASA physical status I-III, by body mass
      index as non-obese (< or = 30 kg x m(-2)) or obese (> 30 kg x m(-2)) and
      randomized them to LMA-C/PLMA or ETT groups for airway management. Anesthesia was
      induced with propofol, fentanyl and succinylcholine or rocuronium. In the LMA
      C/PLMA group we used a size 4 LMA-C in non-obese patients and size 4 or 5 PLMA in
      obese patients. In the ETT group we used a cuffed 7.0 mm ETT in all patients.
      Anesthesia was maintained with isoflurane in nitrous oxide and 30-50% oxygen,
      fentanyl and neuromuscular blockade with mechanical ventilation (tidal volume 10
      mL x kg(-1)). The staff surgeon, blinded to the type of airway, scored stomach
      size on an ordinal scale 0-10 at initial insertion of the laparoscope and
      immediately before the conclusion of the surgical procedure. RESULTS: There were
      no crossovers and no statistically significant differences between LMA-C/PLMA and
      ETT groups for SpO(2,) P(ET)CO(2) or airway pressure before or during peritoneal
      insufflation in short (< or = 15 min) or long (> 15 min) periods of peritoneal
      inflation. Differences between groups with respect to stomach size changes during
      surgery were not statistically significant. CONCLUSION: A correctly placed LMA-C
      or PLMA is as effective as an ETT for positive pressure ventilation without
      clinically important gastric distension in non-obese and obese patients.

PMID- 12514156
TI  - Protection from aspiration with the LMA-ProSeal after vomiting: a case report.
AB  - PURPOSE: To describe a case of vomiting with a laryngeal mask airway ProSeal(TM)
      (PLMA) in situ. The new design features of the PLMA and their role in protection
      from aspiration are discussed. CLINICAL FEATURES: A 27-yr-old female underwent
      bilateral reduction mammoplasty under general anesthesia utilizing a PLMA for
      airway management. During transfer to the postanesthesia care unit, she had an
      episode of active vomiting with the PLMA still in situ. The vomitus was expelled
      via the drain tube bypassing the pharynx entirely. Clinically, there was no
      evidence of aspiration and the patient had an uneventful recovery. CONCLUSION:
      This case provides evidence that the drain tube of the PLMA directs vomitus away
      from the airway when properly positioned and may have prevented aspiration in an
      anesthetized patient.

PMID- 12514157
TI  - Predicting difficult orotracheal intubation in pharyngo-laryngeal disease:
      preliminary results of a composite index.
AB  - PURPOSE: Prediction of difficulty in orotracheal intubation (DI) in patients
      undergoing laryngeal microsurgery should help reduce the morbidity-mortality
      associated with this clinical situation. To establish a simple score to predict
      this difficulty, we studied 11 variables and their association with DI in these
      patients. METHODS: The study included 181 patients. The variables evaluated were:
      Mallampati grade, thyromental distance, mouth opening, temporomandibular joint
      movement, tooth morphology, maxillary deficiency, head and neck movement,
      receding mandible, body mass index, and clinical symptoms of laryngeal and
      supraglottic disease. To establish the score, regression coefficients of the
      statistically significant variables were used on adjusted logistic regression
      analysis. RESULTS: DI was present in 50 patients (28%) and orotracheal intubation
      was impossible in four (2%). Except for obesity, all the variables evaluated were
      predictive of DI. A simple predictive test was established based on logistic
      regression analysis including all the variables except temporomandibular joint
      movement. To determine the optimum cut-off for the new test, a receiver operating
      characteristic curve analysis was applied. A score > or = 5 in the proposed test
      provided a sensitivity of 94% and a specificity of 76%. CONCLUSION: The index we
      describe is aimed at predicting DI in a very specific population with a high risk
      of this complication. This index uses a series of variables which may be measured
      easily during the preoperative period and provides an excellent predictive
      capacity with a high sensitivity and specificity when the index is > or = 5.

PMID- 12514158
TI  - Noxious stimuli do not modify myogenic motor evoked potentials by electrical
      stimulation during anesthesia with propofol-based anesthesia.
AB  - PURPOSE: To investigate whether motor evoked potentials (MEP) to transcranial
      electrical stimulation under constant blood propofol concentration are affected
      by the arousing effect of surgical noxious stimuli. METHODS: Twenty patients who
      underwent elective spinal surgery were studied. Patients were anesthetized with
      50% nitrous oxide in oxygen, fentanyl, and propofol to maintain the bispectral
      index (BIS) score around 50. MEP in response to a multipulse transcranial
      electrical stimulation at stimulus sites of C3-C4 were recorded over the right
      abductor pollicis brevis muscle. Changes of peak-to-peak amplitude and onset
      latency of MEP, BIS score before and after surgical stimuli were evaluated.
      Propofol plasma concentration was measured at the same time points. RESULTS: Both
      MEP amplitude and latency did not change significantly after surgical stimuli
      although BIS increased significantly (48 +/- 6 to 58 +/- 5; P < 0.05). Plasma
      propofol concentration was maintained at the same level between the two
      measurement points (3.3 +/- 0.7 to 3.3 +/- 0.7 micro g*mL(-1)). There was no
      relation between BIS change and changes of MEP amplitude and latency, and
      propofol plasma concentration. CONCLUSION: MEP to the transcranial electrical
      stimulation under a constant and clinically appropriate blood propofol
      concentration are not affected by surgical noxious stimuli.

PMID- 12514159
TI  - Therapy of chronic non-malignant pain with opioids.

PMID- 12514160
TI  - Dopamine for renal protection.

PMID- 12514161
TI  - Erroneous connection of the fresh gas flow to the anesthesia circuit.

PMID- 12514162
TI  - Skin analgesia with lidocaine tape prior to epidural blockade.

PMID- 12514163
TI  - Accidental intravascular injection of levobupivacaine and lidocaine during the
      transarterial approach to the axillary brachial plexus.

PMID- 12514164
TI  - fMRI responses to cold pressor challenges in control and obstructive sleep apnea
      subjects.
AB  - Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which
      may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in
      16 control and 10 OSA subjects who were free of cardiovascular or mood-altering
      drugs to examine neural responses to a forehead cold pressor challenge, which
      elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The
      magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed
      greater intersubject variability and reached a nadir later in OSA patients. Both
      groups showed similar signal changes to cold stimulation in multiple brain sites.
      However, signal increases emerged in OSA over controls in anterior and posterior
      cingulate and cerebellar and frontal cortex, whereas signals markedly declined in
      the ventral thalamus, hippocampus, and insula rather than rising as in controls.
      Anomalous responses often paralleled changes in breathing and heart rate.
      Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed
      lower signals in OSA cases. Cold pressor physiological responses are modified in
      OSA and may result from both diminished and exaggerated responses in multiple
      brain structures.

PMID- 12514165
TI  - Heterogeneous activity of the human genioglossus muscle assessed by multiple
      bipolar fine-wire electrodes.
AB  - Genioglossus (GG) electrical activity [measured by electromyogram (EMGgg)] is
      best measured by intramuscular electrodes; however, the homogeneity of EMGgg is
      undefined. We investigated the relationships between EMGgg and the site from
      which activity was measured to determine whether and to what extent inhomogeneity
      in activity occurred. Eight healthy human volunteers underwent ultrasound to
      determine GG depth and width. Four pairs of electrodes were then inserted
      percutaneously into the left and right GG muscle, anteriorly and posteriorly.
      Additional configurations were obtained by connecting electrodes across the
      midline and along each muscle belly. EMGgg activity was simultaneously recorded
      from these 10 configurations at rest and during various respiratory maneuvers.
      Heterogeneous behavior of the GG was evidenced by 1) the variable presence of
      phasic EMGgg at rest, which was undetectable in two subjects but evident in 65%
      of configurations in six subjects and present in all configurations in all
      subjects during voluntary hyperventilation; 2) a greater amplitude of EMGgg
      response to pharyngeal square-wave negative pressure in anterior than posterior
      configurations (14.1 +/- 7.1 vs. 8.5 +/- 5.1% of maximum, P < 0.05); and 3)
      variable (linear and alinear) relationships between EMGgg and lingual force
      within and between subjects. We hypothesize that regional differences in density
      and type of muscle fiber are the most likely sources of heterogeneity in these
      responses.

PMID- 12514166
TI  - Genetic models in applied physiology: selected contribution: effects of
      spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions.
AB  - There are several aspects of the spaceflight environment that may lead to changes
      in immunity: mission-related psychological stress, radiation, and changes in
      gravity. On December 5, 2001, the space shuttle Endeavor launched for a 12-day
      mission to examine these effects on C57BL/6 mice for the first time. On their
      return, assays were performed on the spleen, blood, and bone marrow. In response
      to flight, there were no significant differences in the general circulating
      leukocyte proportions. In contrast, there was an increase in splenic lymphocyte
      percentages, with a corresponding decrease in granulocytes. There was an overall
      shift in splenic lymphocytes away from T cells toward B cells, and a decrease in
      the CD4-to-CD8 ratios due to a decrease in T helpers. In contrast, there were
      proportional increases in bone marrow T cells, with decreases in B cells.
      Although the blast percentage and count were decreased in flight mice, the
      CD34(+) population was increased. The data were more consistent with a shift in
      bone marrow populations rather than a response to changes in the periphery. Many
      of the results are similar to those using other models. Clearly, spaceflight can
      influence immune parameters ranging from hematopoiesis to mature leukocyte
      mechanisms.

PMID- 12514167
TI  - Catecholaminergic microcircuitry controlling the output of airway-related vagal
      preganglionic neurons.
AB  - In this study, we have investigated the ultrastructure and function of the
      catecholaminergic circuitry modulating the output of airway-related vagal
      preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed
      to characterize the nature of catecholaminergic innervation of AVPN at the
      ultrastructural level. In addition, immunofluorescence was used to examine the
      expression of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) on AVPNs, and
      norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by
      using microdialysis. Physiological experiments were performed to determine the
      effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on
      airway smooth muscle tone. The results showed that 1) catecholaminergic nerve
      endings terminate in the vicinity of identified AVPNs but very rarely form
      axosomatic or axodendritic synapses with the AVPNs that innervate the
      extrathoracic trachea; 2) AVPNs express the alpha(2A)-AR; 3) LC stimulation
      induced norepinephrine release within the rNA region was associated with airway
      smooth muscle relaxation; and 4) blockade of alpha(2A)-AR on AVPNs diminished the
      inhibitory effects of LC stimulation on airway smooth muscle tone. It is
      concluded that a noradrenergic circuit originating within the LC is involved in
      the regulation of AVPN activity within the rNA, and stimulation of the LC dilates
      the airways by the release of norepinephrine and activation of alpha(2A)-AR
      expressed by AVPNs, mainly via volume transmission.

PMID- 12514168
TI  - Phosphocreatine content of freeze-clamped muscle: influence of creatine kinase
      inhibition.
AB  - The study of cellular energetics is critically dependent on accurate measurement
      of high-energy phosphates. Muscle values of phosphocreatine (PCr) vary greatly
      between in vivo measurements (i.e., by nuclear magnetic resonance) and chemical
      measurements determined from muscles isolated and quick-frozen. The source of
      this difference has not been experimentally identified. A likely cause is
      activation of ATPases and phosphotransfer from PCr to ADP. Therefore, rat
      hindlimb skeletal muscle was perfused either with or without 2 mM iodoacetamide,
      a creatine kinase inhibitor, and muscle was freeze-clamped either at rest or
      after contraction. Creatine kinase inhibition resulted in approximately 6
      micromol/g higher PCr and lower creatine in the freeze-clamped soleus, red
      gastrocnemius, and white gastrocnemius. This PCr content difference was reduced
      when the initial PCr content was decreased with prior contractions. Therefore,
      the amount of PCr artifact appears to scale with initial PCr content within a
      fiber-type section. This artifact directly affects the measurement and, thus, the
      calculations of muscle energetic parameters from studies using isolated and
      frozen muscle.

PMID- 12514169
TI  - Host recognition of bacterial muramyl dipeptide mediated through NOD2.
      Implications for Crohn's disease.
AB  - NOD2, a protein associated with susceptibility to Crohn's disease, confers
      responsiveness to bacterial preparations of lipopolysaccharide and peptidoglycan,
      but the precise moiety recognized remains elusive. Biochemical and functional
      analyses identified muramyl dipeptide (MurNAc-L-Ala-D-isoGln) derived from
      peptidoglycan as the essential structure in bacteria recognized by NOD2.
      Replacement of L-Ala for D-Ala or D-isoGln for L-isoGln eliminated the ability of
      muramyl dipeptide to stimulate NOD2, indicating stereoselective recognition.
      Muramyl dipeptide was recognized by NOD2 but not by TLR2 or co-expression of TLR2
      with TLR1 or TLR6. NOD2 mutants associated with susceptibility to Crohn's disease
      were deficient in their recognition of muramyl dipeptide. Notably, peripheral
      blood mononuclear cells from individuals homozygous for the major disease
      associated L1007fsinsC NOD2 mutation responded to lipopolysaccharide but not to
      synthetic muramyl dipeptide. Thus, NOD2 mediates the host response to bacterial
      muropeptides derived from peptidoglycan, an activity that is important for
      protection against Crohn's disease. Because muramyl dipeptide is the essential
      structure of peptidoglycan required for adjuvant activity, these results also
      have implications for understanding adjuvant function and effective vaccine
      development.

PMID- 12514170
TI  - Visualizing superoxide production in normal and diabetic rat islets of
      Langerhans.
AB  - Oxygen free radicals have been implicated in beta-cell dysfunction and apoptosis
      associated with type 1 and type 2 diabetes mellitus. The roles of free radicals
      in diabetes have thus far been defined indirectly by monitoring oxidative tissue
      damage and the effects of antioxidants, free radical scavengers, and
      overexpression of superoxide dismutase. We employed the superoxide-mediated
      oxidation of hydroethidine to ethidium to dynamically and directly assess the
      relative rates of mitochondrial superoxide anion generation in isolated islets in
      response to glucose stimulation. Superoxide content of isolated islets increased
      in response to glucose stimulation. We next compared the oxyradical levels in
      Zucker lean control and Zucker diabetic fatty rat islets by digital imaging
      microfluorometry. The superoxide content of Zucker diabetic fatty islets was
      significantly higher than Zucker lean control islets under resting conditions,
      relatively insensitive to elevated glucose concentrations, and correlated
      temporally with a decrease in glucose-induced hyperpolarization of the
      mitochondrial membrane. Importantly, superoxide levels were elevated in islets
      from young, pre-diabetic Zucker diabetic fatty animals. Overproduction of
      superoxide was associated with perturbed mitochondrial morphology and may
      contribute to abnormal glucose signaling found in the Zucker diabetic fatty model
      of type 2 diabetes mellitus.

PMID- 12514171
TI  - Phosphatidylinositol 4,5-bisphosphate (PIP2) modulation of ATP and pH sensitivity
      in Kir channels. A tale of an active and a silent PIP2 site in the N terminus.
AB  - Phosphatidylinositol polyphosphates (PIPs) are potent modulators of Kir channels.
      Previous studies have implicated basic residues in the C terminus of Kir6.2
      channels as interaction sites for the PIPs. Here we examined the role of the N
      terminus and identified an arginine (Arg-54) as a major determinant for PIP(2)
      modulation of ATP sensitivity in K(ATP) channels. Mutation of Arg-54 to the
      neutral glutamine (R54Q) and, in particular, to the negatively charged glutamate
      (R54E) impaired PIP(2) modulation of ATP inhibition, while mutation to lysine
      (R54K) had no effect. These data suggest that electrostatic interactions between
      PIP(2) and Arg-54 are an essential step for the modulation of ATP sensitivity.
      This N-terminal PIP(2) site is highly conserved in Kir channels with the
      exception of the pH-gated channels Kir1.1, Kir4.1, and Kir5.1 that contain a
      neutral residue at the corresponding positions. Introduction of an arginine at
      this position in Kir1.1 channels rendered the N-terminal PIP(2) site functional
      largely increasing the PIP(2) affinity. Moreover, Kir1.1 channels lose the
      ability to respond to physiological changes of the intracellular pH. These
      results explain the need of a silent N-terminal PIP(2) site in pH-gated channels
      and highlight the N terminus as an important region for PIP(2) modulation of Kir
      channel gating.

PMID- 12514172
TI  - PYK2 autophosphorylation, but not kinase activity, is necessary for adhesion
      induced association with c-Src, osteoclast spreading, and bone resorption.
AB  - Proline-rich tyrosine kinase 2 (PYK2) is the main adhesion-induced kinase in bone
      resorbing osteoclasts. Previous studies have shown that ligation of
      alpha(v)beta(3) integrin in osteoclasts induces c-Src-dependent tyrosine
      phosphorylation and PYK2 activation, leading to cytoskeletal rearrangement,
      migration, and polarization of these cells. In this study, we examined the role
      of PYK2 kinase activity and its major autophosphorylation site in adhesion
      dependent signaling and cytoskeletal organization during osteoclast spreading and
      migration. By infecting pre-fusion osteoclasts using recombinant adenovirus
      expressing PYK2 and its mutants, we demonstrated that mutation at the
      autophosphorylation site (Y402F) abolishes PYK2 association with c-Src and
      reduces significantly phosphorylation at tyrosines 579/580 and 881 resulting in
      inhibition of osteoclast spreading and bone resorption. Overexpression of the
      kinase-dead PYK2(K475A) mutant had no effect on cell spreading, interaction with
      c-Src, or the phosphorylation level of Tyr-402, Tyr-579/580, and Tyr-881 relative
      to PYK2(wt)-expressing cells. Taken together these findings suggest that Tyr-402
      is the major docking site for c-Src and can be phosphorylated by another tyrosine
      kinase in osteoclasts but not in HEK293 cells. Interestingly, both PYK2(Y402F)
      and PYK2(K457A) translocate normally to podosomes and have no effect on
      macrophage colony-stimulating factor-induced osteoclast migration. Whereas
      PYK2(Y402F) dominant negatively blocks osteoclast spreading and bone resorption,
      PYK2(K457A) may function in part as an adaptor by initially recruiting c-Src to
      the adhesion complex, which appears to activate PYK2 by phosphorylating
      additional tyrosines in its regulatory and C-terminal domains. We thus concluded
      that phosphorylation at Tyr-402 in PYK2 is essential in the regulation of
      adhesion-dependent cytoskeletal organization in osteoclasts.

PMID- 12514173
TI  - Molecular dissection of the hydrophobic segments H3 and H4 of the yeast Ca2+
      channel component Mid1.
AB  - The Saccharomyces cerevisiae MID1 gene product, Mid1, is composed of 548 amino
      acid residues, has four relatively hydrophobic segments named H1-H4, and
      functions as a Ca(2+)-permeable, stretch-activated channel when expressed in
      mammalian cells. In some conditions Mid1 cooperates with Cch1, a yeast homolog of
      the alpha1 subunit of mammalian voltage-gated channels. To identify the important
      regions or amino acid residues necessary for Mid1 function, we employed in vitro
      site-directed mutagenesis on H3 and H4 of Mid1 and expressed the resulting mutant
      genes in a mid1 null mutant to examine whether the mutant gene products are
      functional or not in vivo. Mutant Mid1 proteins lacking the whole H3 or H4
      segment, H3De or H4De, did not complement the lethality and low Ca(2+)
      accumulation activity of the mid1 mutant, although their localization and
      contents appeared to be normal, indicating that H3 and H4 are required for Mid1
      function itself. Single amino acid exchange experiments on individual amino acid
      residues of H3 and H4 showed that 10 of 20 residues in H3 and 14 of 23 residues
      in H4 were important for the normal function of Mid1. In particular, we found
      four severe loss-of-function mutations, D341E, F356S, C373D, and C373R, and two
      interesting mutations leading to a high level of Ca(2+) accumulation with a
      slightly low complementing activity, G342A and Y355A. The importance of these
      amino acid residues will be discussed.

PMID- 12514174
TI  - JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and
      inhibits WOX1-mediated apoptosis.
AB  - Transient activation of c-Jun N-terminal kinase (JNK) promotes cell survival,
      whereas persistent JNK activation induces apoptosis. Bovine testicular
      hyaluronidase PH-20 activates JNK1 and protects L929 fibroblasts from
      staurosporine-mediated cell death. PH-20 also induces the expression of a p53
      interacting WW domain-containing oxidoreductase (WOX1, also known as WWOX or FOR)
      in these cells. WOX1 enhances the cytotoxic function of tumor necrosis factor and
      mediates apoptosis synergistically with p53. Thus, the activated JNK1 is likely
      to counteract WOX1 in mediating apoptosis. Here it is demonstrated that ectopic
      JNK1 inhibited WOX1-mediated apoptosis of L929 fibroblasts, monocytic U937 cells,
      and other cell types. Also, JNK1 blocked WOX1 prevention of cell cycle
      progression. By stimulating cells with anisomycin or UV light, JNK1 became
      activated, and WOX1 was phosphorylated at Tyr(33). The activated JNK1 physically
      interacted with the phosphorylated WOX1, as determined by co-immunoprecipitation.
      Alteration of Tyr(33) to Arg(33) in WOX1 abrogated its binding interaction with
      JNK1 and its activity in mediating cell death, indicating that Tyr(33)
      phosphorylation is needed to activate WOX1. A dominant negative WOX1 was
      developed and shown to block p53-mediated apoptosis and anisomycin-mediated WOX1
      phosphorylation but could not inhibit JNK1 activation. This mutant protein bound
      p53 but could not interact with JNK1, as determined in yeast two-hybrid analysis.
      Taken together, phosphorylation of JNK1 and WOX1 is necessary for their physical
      interaction and functional antagonism.

PMID- 12514175
TI  - Growth differentiation factor-15 prevents low potassium-induced cell death of
      cerebellar granule neurons by differential regulation of Akt and ERK pathways.
AB  - Growth differentiation factor-15 (GDF-15) is a novel member of the transforming
      growth factor-beta superfamily and has been shown to be induced in neurons
      subsequent to lesions. We have therefore begun to study its putative role in the
      regulation of neuron survival and apoptosis. Cultured cerebellar granule neurons
      (CGN) survive when maintained in high K(+) (25 mm) but undergo apoptosis when
      switched to low K(+) (5 mm). GDF-15 prevented death of CGN in low K(+). This
      effect could be blocked by phosphatidylinositol 3-kinase/Akt pathway inhibitors
      LY294002 or wortmannin. In contrast, mitogen-activated protein kinase
      (MEK)/extracellular-signal-regulated kinase (ERK) pathway inhibitors U0126 and
      PD98059 potentiated GDF-15 mediated survival and prevented cell death in low K(+)
      even without factor treatment. Immunoblots revealed GDF-15-induced
      phosphorylation of Akt and glycogen synthase kinase-3beta. This activation was
      suppressed by phosphatidylinositol 3-kinase inhibitors. Low K(+) induced delayed
      and persistent ERK activation, which was blocked by MEK inhibitors or GDF-15. ERK
      activation induced c-Jun, a member of the AP-1 transcription factor family. GDF
      15 or U0126 prevented c-Jun activation. Furthermore, we show that GDF-15
      prevented generation of reactive oxygen species, a known activator of ERK.
      Together, our data suggest that GDF-15 prevents apoptosis in CGN by activating
      Akt and inhibiting endogenously active ERK.

PMID- 12514176
TI  - Decoding of short-lived Ca2+ influx signals into long term substrate
      phosphorylation through activation of two distinct classes of protein kinase C.
AB  - In electrically excitable cells, membrane depolarization opens voltage-dependent
      Ca(2+) channels eliciting Ca(2+) influx, which plays an important role for the
      activation of protein kinase C (PKC). However, we do not know whether Ca(2+)
      influx alone can activate PKC. The present study was conducted to investigate the
      Ca(2+) influx-induced activation mechanisms for two classes of PKC, conventional
      PKC (cPKC; PKCalpha) and novel PKC (nPKC; PKCtheta), in insulin-secreting cells.
      We have demonstrated simultaneous translocation of both DsRed-tagged PKCalpha to
      the plasma membrane and green fluorescent protein (GFP)-tagged myristoylated
      alanine-rich C kinase substrate to the cytosol as a dual marker of PKC activity
      in response to depolarization-evoked Ca(2+) influx in the DsRed-tagged PKCalpha
      and GFP-tagged myristoylated alanine-rich C kinase substrate co-expressing cells.
      The result indicates that Ca(2+) influx can generate diacylglycerol (DAG),
      because cPKC is activated by Ca(2+) and DAG. We showed this in three different
      ways by demonstrating: 1) Ca(2+) influx-induced translocation of GFP-tagged C1
      domain of PKCgamma, 2) Ca(2+) influx-induced translocation of GFP-tagged
      pleckstrin homology domain, and 3) Ca(2+) influx-induced translocation of GFP
      tagged PKCtheta, as a marker of DAG production and/or nPKC activity. Thus, Ca(2+)
      influx alone via voltage-dependent Ca(2+) channels can generate DAG, thereby
      activating cPKC and nPKC, whose activation is structurally independent of Ca(2+).

PMID- 12514177
TI  - Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint
      formation with chromatin.
AB  - In eukaryotic cells, the repair of DNA double-strand breaks by homologous
      recombination requires a RecA-like recombinase, Rad51p, and a Swi2p/Snf2p-like
      ATPase, Rad54p. Here we find that yeast Rad51p and Rad54p support robust
      homologous pairing between single-stranded DNA and a chromatin donor. In
      contrast, bacterial RecA is incapable of catalyzing homologous pairing with a
      chromatin donor. We also show that Rad54p possesses many of the biochemical
      properties of bona fide ATP-dependent chromatin-remodeling enzymes, such as
      ySWI/SNF. Rad54p can enhance the accessibility of DNA within nucleosomal arrays,
      but it does not seem to disrupt nucleosome positioning. Taken together, our
      results indicate that Rad54p is a chromatin-remodeling enzyme that promotes
      homologous DNA pairing events within the context of chromatin.

PMID- 12514178
TI  - Pyridoxal phosphate inhibits dynamic subunit interchange among serine
      hydroxymethyltransferase tetramers.
AB  - Cytoplasmic serine hydroxymethyltransferase (cSHMT) is a tetrameric, pyridoxal
      phosphate (PLP)-dependent enzyme that catalyzes the reversible interconversion of
      serine and tetrahydrofolate to glycine and methylenetetrahydrofolate. The enzyme
      has four active sites and is best described as a dimer of obligate dimers. Each
      monomeric subunit within the obligate dimer contributes catalytically important
      amino acid residues to both active sites. To investigate the interchange of
      subunits among cSHMT tetramers, a dominant-negative human cSHMT enzyme (DNcSHMT)
      was engineered by making three amino acid substitutions: K257Q, Y82A, and Y83F.
      Purified recombinant DNcSHMT protein was catalytically inactive and did not bind
      5-formyltetrahydrofolate. Coexpression of the cSHMT and DNcSHMT proteins in
      bacteria resulted in the formation of heterotetramers with a cSHMT/DNcSHMT
      subunit ratio of 1. Characterization of the cSHMT/DNcSHMT heterotetramers
      indicates that DNcSHMT and cSHMT monomers randomly associate to form tetramers
      and that cSHMT/DNcSHMT obligate dimers are catalytically inactive. Incubation of
      recombinant cSHMT protein with recombinant DNcSHMT protein did not result in the
      formation of hetero-oligomers, indicating that cSHMT subunits do not exchange
      once the tetramer is assembled. However, removal of the active site PLP cofactor
      does permit exchange of obligate dimers among preformed cSHMT and DNcSHMT
      tetramers, and the formation of heterotetramers from cSHMT and DNcSHMT homodimers
      does not affect the activity of the cSHMT homodimers. The results of these
      studies demonstrate that PLP inhibits dimer exchange among cSHMT tetramers and
      suggests that cellular PLP concentrations may influence the stability of cSHMT
      protein in vivo.

PMID- 12514179
TI  - Phycocyanobilin:ferredoxin oxidoreductase of Anabaena sp. PCC 7120. Biochemical
      and spectroscopic.
AB  - In cyanobacteria, the biosynthesis of the phycobiliprotein and phytochrome
      chromophore precursor phycocyanobilin is catalyzed by the ferredoxin-dependent
      enzyme phycocyanobilin:ferredoxin oxidoreductase (PcyA), which mediates an
      atypical four-electron reduction of biliverdin IXalpha. Here we describe the
      expression, affinity purification, and biochemical characterization of
      recombinant PcyA from Anabaena sp. PCC 7120. A monomeric protein with a native
      M(r) of 30,400 +/- 5,000, recombinant PcyA forms a tight and stable
      stoichiometric complex with its substrate biliverdin IXalpha. The enzyme exhibits
      a strong preference for plant type [2Fe-2S] ferredoxins; however, flavodoxin can
      also serve as an electron donor. HPLC analyses establish that catalysis proceeds
      via the two electron-reduced intermediate 18(1),18(2)-dihydrobiliverdin,
      indicating that exovinyl reduction precedes A-ring (endovinyl) reduction.
      Substrate specificity studies indicate that the arrangement of the A- and D-ring
      substituents alters the positioning of the bilin substrate within the enzyme,
      profoundly influencing the course of catalysis. Based on these observations and
      the apparent lack of a metal or small molecule cofactor, a radical mechanism for
      biliverdin IXalpha reduction by phycocyanobilin:ferredoxin oxidoreductase is
      envisaged.

PMID- 12514180
TI  - Cell cycle regulation and p53 activation by protein phosphatase 2C alpha.
AB  - Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates,
      regulating stress response and growth-related pathways in both prokaryotes and
      eukaryotes. We now demonstrate that PP2C alpha, a major mammalian isoform,
      inhibits cell growth and activates the p53 pathway. In 293 cell clones, in which
      PP2C alpha expression is regulated by a tetracycline-inducible promoter, PP2C
      alpha overexpression led to G(2)/M cell cycle arrest and apoptosis. Furthermore,
      PP2C alpha induced the expression of endogenous p53 and the p53-responsive gene
      p21. Activation of the p53 pathway by PP2C alpha took place both in cells
      harboring endogenous p53, as well as in p53-null cells transfected with exogenous
      p53. Induction of PP2C alpha resulted in an increase in the overall levels of p53
      protein as well as an augmentation of p53 transcription activity. The
      dephosphorylation activity of PP2C alpha is essential to the described phenomena,
      as none of these effects was detected when an enzymatically inactive PP2C alpha
      mutant was overexpressed. p53 plays an important role in PP2C alpha-directed cell
      cycle arrest and apoptosis because perturbation of p53 expression in human 293
      cells by human papillomavirus E6 led to a significant increase in cell survival.
      The role of PP2C alpha in p53 activation is discussed.

PMID- 12514181
TI  - Molecular recognition in helix-loop-helix and helix-loop-helix-leucine zipper
      domains. Design of repertoires and selection of high affinity ligands for natural
      proteins.
AB  - Helix-loop-helix (HLH) and helix-loop-helix-leucine zipper (HLHZip) are
      dimerization domains that mediate selective pairing among members of a large
      transcription factor family involved in cell fate determination. To investigate
      the molecular rules underlying recognition specificity and to isolate molecules
      interfering with cell proliferation and differentiation control, we assembled two
      molecular repertoires obtained by directed randomization of the binding surface
      in these two domains. For this strategy we selected the Heb HLH and Max Zip
      regions as molecular scaffolds for the randomization process and displayed the
      two resulting molecular repertoires on lambda phage capsids. By affinity
      selection, many domains were isolated that bound to the proteins Mad, Rox, MyoD,
      and Id2 with different levels of affinity. Although several residues along an
      extended surface within each domain appeared to contribute to dimerization, some
      key residues critically involved in molecular recognition could be identified.
      Furthermore, a number of charged residues appeared to act as switch points
      facilitating partner exchange. By successfully selecting ligands for four of four
      HLH or HLHZip proteins, we have shown that the repertoires assembled are rather
      general and possibly contain elements that bind with sufficient affinity to any
      natural HLH or HLHZip molecule. Thus they represent a valuable source of ligands
      that could be used as reagents for molecular dissection of functional regulatory
      pathways.

PMID- 12514182
TI  - Bipartite signals mediate subcellular targeting of tail-anchored membrane
      proteins in Saccharomyces cerevisiae.
AB  - Tail-anchored proteins have an NH(2)-terminal cytosolic domain anchored to
      intracellular membranes by a single, COOH-terminal, transmembrane segment.
      Sequence analysis identified 55 tail-anchored proteins in Saccharomyces
      cerevisiae, with several novel proteins, including Prm3, which we find is
      required for karyogamy and is tail-anchored in the nuclear envelope. A total of
      six tail-anchored proteins are present in the mitochondrial outer membrane and
      have relatively hydrophilic transmembrane segments that serve as targeting
      signals. The rest, by far the majority, localize via a bipartite system of
      signals: uniformly hydrophobic tail anchors are first inserted into the
      endoplasmic reticulum, and additional segments within the cytosolic domain of
      each protein can dictate subsequent sorting to a precise destination within the
      cell.

PMID- 12514183
TI  - Malignant transformation of melanocytes to melanoma by constitutive activation of
      mitogen-activated protein kinase kinase (MAPKK) signaling.
AB  - Malignant melanoma is the cancer with the most rapid increase in incidence in the
      United States. Ultraviolet light and deficiency of the p16ink4a gene are known
      factors that predispose one to the development of malignant melanoma. The signal
      transduction pathways that underlie the progression of melanoma from their
      precursors, atypical nevi, are not well understood. We examined activation of the
      MAP kinase pathway in atypical nevi and melanoma cells and found that this
      pathway is activated in melanomas. To determine the functional significance of
      this activation, we introduced constitutively active MAP kinase kinase (MAPKK)
      into immortalized melanocytes. The introduction of this gene into melanocytes
      leads to tumorigenesis in nude mice, activation of the angiogenic switch, and
      increased production of the proangiogenic factor, vascular endothelial growth
      factor (VEGF), and matrix metalloproteinases (MMPs). Activation of MAP kinase
      signaling may be an important pathway involved in melanoma transformation.
      Inhibition of MAP kinase signaling may be useful in the prevention and treatment
      of melanoma.

PMID- 12514184
TI  - Catalytic mechanism of thiol peroxidase from Escherichia coli. Sulfenic acid
      formation and overoxidation of essential CYS61.
AB  - Escherichia coli thiol peroxidase (Tpx, p20, scavengase) is part of an oxidative
      stress defense system that uses reducing equivalents from thioredoxin (Trx1) and
      thioredoxin reductase to reduce alkyl hydroperoxides. Tpx contains three Cys
      residues, Cys(95), Cys(82), and Cys(61), and the latter residue aligns with the N
      terminal active site Cys of other peroxidases in the peroxiredoxin family. To
      identify the catalytically important Cys, we have cloned and purified Tpx and
      four mutants (C61S, C82S, C95S, and C82S,C95S). In rapid reaction kinetic
      experiments measuring steady-state turnover, C61S is inactive, C95S retains
      partial activity, and the C82S mutation only slightly affects reaction rates.
      Furthermore, a sulfenic acid intermediate at Cys(61) generated by cumene
      hydroperoxide (CHP) treatment was detected in UV-visible spectra of 4-nitrobenzo
      2-oxa-1,3-diazole-labeled C82S,C95S, confirming the identity of Cys(61) as the
      peroxidatic center. In stopped-flow kinetic studies, Tpx and Trx1 form a
      Michaelis complex during turnover with a catalytic efficiency of 3.0 x 10(6) m(
      1) s(-1), and the low K(m) (9.0 microm) of Tpx for CHP demonstrates substrate
      specificity toward alkyl hydroperoxides over H(2)O(2) (K(m) > 1.7 mm). Rapid
      inactivation of Tpx due to Cys(61) overoxidation is observed during turnover with
      CHP and a lipid hydroperoxide, 15-hydroperoxyeicosatetraenoic acid, but not
      H(2)O(2). Unlike most other 2-Cys peroxiredoxins, which operate by an
      intersubunit disulfide mechanism, Tpx contains a redox-active intrasubunit
      disulfide bond yet is homodimeric in solution.

PMID- 12514185
TI  - Proline oxidase induces apoptosis in tumor cells, and its expression is
      frequently absent or reduced in renal carcinomas.
AB  - Proline oxidase is a p53-induced gene that can mediate apoptosis in lung
      carcinoma cells. Here, we provide evidence implicating a role for proline oxidase
      in renal carcinoma. We observed absent or reduced expression of proline oxidase
      in 8 of 12 primary renal cell carcinomas, with respect to their normal tissue
      counterparts. Two renal cell carcinomas, which displayed little or no expression
      of proline oxidase, expressed p53s that were less capable of inducing proline
      oxidase than p53 isolated from normal renal tissue. One of those tumor-derived
      p53s contained a double transition mutation at amino acid residues 125 (Ala to
      Thr) and 193 (Arg to His), and the other exhibited a single transition mutation
      at amino acid 149 (Ser to Phe). Forced up-regulation of proline oxidase induced
      the formation of reactive oxygen species and mediated apoptosis in the 786-0
      renal cell carcinoma cell line. A proline oxidase antisense vector repressed p53
      induced up-regulation of proline oxidase, release of cytochrome c from
      mitochondria, and apoptosis in 786-0 renal carcinoma cells. Taken together, these
      findings support a role for proline oxidase as a downstream effector in p53
      mediated apoptosis. We hypothesize that its altered expression can contribute to
      the development of renal carcinomas. The presence of proline oxidase in
      mitochondria, a primary organelle that regulates apoptosis, places this molecule
      in a subcellular localization that can directly influence the apoptotic pathway
      and thus tumorigenesis.

PMID- 12514186
TI  - Sonic hedgehog induces capillary morphogenesis by endothelial cells through
      phosphoinositide 3-kinase.
AB  - Sonic hedgehog (Shh) acts as a morphogen in many cell types. Recent studies have
      shown that hedgehog signaling is involved in vascular development as well as
      postnatal angiogenesis. However, the direct action of Shh on cultured endothelial
      cells has not been clearly shown. To address this issue, we examined the effect
      of Shh on morphological changes by murine brain capillary endothelial cells (IBE
      cells) and human umbilical endothelial cells (HUVECs). Shh induced capillary
      morphogenesis by these cells. The effect was inhibited by cyclopamine or
      pertussis toxin. Shh-induced capillary morphogenesis was also blocked by
      LY294002, a phosphoinositide 3-kinase (PI3-kinase) inhibitor. Shh rapidly
      increased PI3-kinase activity in IBE cells and HUVECs; this activity was
      inhibited by cyclopamine. Nuclear localization of Gli1 was increased in Shh
      treated IBE cells, which was not affected by LY294002. Actinomycin D and
      cycloheximide inhibited Shh-induced capillary morphogenesis. In IBE cells
      expressing kinase-inactive c-Fes, Shh failed to stimulate PI3-kinase activity and
      capillary morphogenesis. Considered collectively, Shh induced capillary
      morphogenesis of endothelial cells through both rapid activation of c-Fes/PI3
      kinase pathways and transcriptionally regulated pathways.

PMID- 12514187
TI  - Characterization of prominin-2, a new member of the prominin family of pentaspan
      membrane glycoproteins.
AB  - Prominin/CD133 is a 115/120-kDa integral membrane glycoprotein specifically
      associated with plasma membrane protrusions in epithelial and non-epithelial
      cells including neuroepithelial and hematopoietic stem cells. Here we report the
      identification as well as molecular and cell biological characterization of
      mouse, rat, and human prominin-2, a 112-kDa glycoprotein structurally related to
      prominin (referred to as prominin-1). Although the amino acid identity between
      prominin-2 and prominin-1 is low (<30%), their genomic organization is strikingly
      similar, suggesting an early gene duplication event. Like prominin-1, prominin-2
      exhibits a characteristic membrane topology with five transmembrane segments and
      two large glycosylated extracellular loops. Upon its ectopic expression in
      Chinese hamster ovary cells as a green fluorescent protein fusion chimera,
      prominin-2 was also found to be associated with plasma membrane protrusions, as
      revealed by its co-localization with prominin-1, suggesting a related role.
      Consistent with this, prominin-2 shows a similar tissue distribution to prominin
      1, being highly expressed in the adult kidney and detected all along the
      digestive tract as well as in various other epithelial tissues. However, in
      contrast to prominin-1, prominin-2 was not detected in the eye, which perhaps
      explains why a loss-of function mutation in the human prominin-1 gene causes
      retinal degeneration but no other obvious pathological signs. Finally, we present
      evidence for the existence of a family of pentaspan membrane proteins, the
      prominins, which are conserved in evolution.

PMID- 12514188
TI  - Protein domains, catalytic activity, and subcellular distribution of neuropathy
      target esterase in Mammalian cells.
AB  - Neuropathy target esterase (NTE), the human homologue of a protein required for
      brain development in Drosophila, has a predicted amino-terminal transmembrane
      helix (TM), a putative regulatory (R) domain, and a hydrophobic catalytic (C)
      domain. Here we describe the expression, in COS cells, of green fluorescent
      protein-tagged constructs of NTE and mutant proteins lacking the TM or the R- or
      C-domains. Esterase assays and Western blots of particulate and soluble fractions
      indicated that neither the TM nor R-domain is essential for NTE catalytic
      activity but that this activity requires membrane association to which the TM, R
      , and C-domains all contribute. Experiments involving proteinase treatment
      revealed that most of the NTE molecule is exposed on the cytoplasmic face of
      membranes. In cells expressing a moderate level of NTE and all cells expressing
      DeltaC-NTE, fluorescence was distributed in an endoplasmic reticulum (ER)-like
      pattern. Cells expressing high levels of NTE showed aberrant distribution of ER
      marker proteins and accumulation of NTE on the cytoplasmic surface of ER-derived
      tubuloreticular aggregates. Deformation of the ER was also seen in cells
      expressing DeltaR-NTE or enzymatically inactive S966A-NTE but not DeltaTM-NTE.
      The data suggest that NTE is anchored in the ER via its TM, that its R- and C
      domains also interact with the cytoplasmic face of the ER, and that
      overexpression of NTE causes ER aggregation via intermolecular association of its
      C-domains.

PMID- 12514189
TI  - Characterization of ADAMTS-9 and ADAMTS-20 as a distinct ADAMTS subfamily related
      to Caenorhabditis elegans GON-1.
AB  - We demonstrate that in humans, two metalloproteases, ADAMTS-9 (1935 amino acids)
      and ADAMTS-20 (1911 amino acids) are orthologs of GON-1, an ADAMTS protease
      required for gonadal morphogenesis in Caenorhabditis elegans. ADAMTS-9 and ADAMTS
      20 have an identical modular structure, are distinct in possessing 15 TSRs and a
      unique C-terminal domain, and have a similar gene structure, suggesting that they
      comprise a new subfamily of human ADAMTS proteases. ADAMTS20 is very sparingly
      expressed, although it is detectable in epithelial cells of the breast and lung.
      However, ADAMTS9 is highly expressed in embryonic and adult tissues, and
      therefore we characterized the ADAMTS-9 protein further. Although the ADAMTS-9
      zymogen has many proprotein convertase processing sites, pulse-chase analysis,
      site-directed mutagenesis, and amino acid sequencing demonstrated that maturation
      to the active form occurs by selective proprotein convertase (e.g. furin)
      cleavage of the Arg(287)-Phe(288) bond. Although lacking a transmembrane
      sequence, ADAMTS-9 is retained near the cell surface as well as in the ECM of
      transiently transfected COS-1 and 293 cells. COS-1 cells transfected with ADAMTS9
      (but not vector-transfected cells) proteolytically cleaved bovine versican and
      aggrecan core proteins at the Glu(441)-Ala(442) bond of versican V1 and the
      Glu(1771)-Ala(1772) bond of aggrecan, respectively. In contrast, the ADAMTS-9
      catalytic domain alone was neither localized to the cell surface nor able to
      confer these proteolytic activities on cells, demonstrating that the ancillary
      domains of ADAMTS-9, including the TSRs, are required both for specific
      extracellular localization and for its versicanase and aggrecanase activities.

PMID- 12514190
TI  - Cloning and characterization of a novel GRP78-binding protein in the rat brain.
AB  - The full-length cDNA clone of a novel GRP78-binding protein (GBP) was isolated
      from rat brain using PCR-selected cDNA subtraction. GBP was predominantly
      expressed in neuronal cells among various brain tissues. GBP mRNA was already
      detected in the E12 brain and then gradually increased to reach a peak within P0
      2 weeks after birth. GBP expression in the brain decreased age-dependently to
      approximately 30% of the postnatal level at 12 months. GBP encoded 1021 amino
      acids and was predicted to have two transmembrane regions and glutamic acid- and
      proline-rich regions. Because the sequence of GBP offered few clues to the
      possible function, we performed a GST-tagged GBP pull-down assay in PC12 lysates
      and identified GRP78, one of the heat shock proteins, as a counterpart.
      Observation of COS7 cells expressing green fluorescent protein- or Myc-tagged GBP
      showed that GBP was localized in the endoplasmic reticulum-Golgi domain where
      BODIPY 558/568 (4,4-difluro-5-(2-thienyl)-4-bora-3alpha,4alpha-diaza-S-indacene)
      labeled brefeldin A accumulated. To investigate a biological role for GBP, we
      established Neuro2a cells stably expressing Myc-tagged GBP. Overexpression of GBP
      did not affect cell growth or morphological features but attenuated the time
      dependent decrease in cell viability caused by serum deprivation compared with
      control cells. After 48 h of serum starvation, Neuro2a cells overexpressing GBP
      were resistant to the cell death induced by serum withdrawal. These results
      suggest that GBP would have a relevant functional role in embryonic and postnatal
      development of the brain.

PMID- 12514191
TI  - Identification of the human and bovine ATP:Cob(I)alamin adenosyltransferase cDNAs
      based on complementation of a bacterial mutant.
AB  - In humans, deficiencies in coenzyme B12-dependent methylmalonyl-CoA mutase (MCM)
      lead to methylmalonyl aciduria, a rare disease that is often fatal in newborns.
      Such deficiencies can result from inborn errors in the MCM structural gene or
      from mutations that impair the assimilation of dietary cobalamins into coenzyme
      B12 (Ado-B12), the required cofactor for MCM. ATP:cob(I)alamin
      adenosyltransferase (ATR) catalyzes the terminal step in the conversion of
      cobalamins into Ado-B12. Substantial evidence indicates that inherited defects in
      this enzyme lead to methylmalonyl aciduria, but the corresponding ATR gene has
      not been identified. Here we report the identification of the bovine and human
      ATR cDNAs as well as the corresponding human gene. A bovine liver cDNA expression
      library was screened for clones that complemented an ATR-deficient bacterial
      strain for color formation on aldehyde indicator medium, and four positive clones
      were isolated. The DNA sequences of two clones were determined and found to be
      identical. Sequence similarity searching was then used to identify a homologous
      human cDNA (89% identity) and its corresponding gene that is located on
      chromosome XII. The bovine and human cDNAs were independently cloned and
      expressed in Escherichia coli. Enzyme assays showed that expression strains
      produced 87 and 98 nmol/min/mg ATR activity, respectively. These specific
      activities are in line with values reported previously for bacterial ATR enzymes.
      Subsequent studies showed that the human cDNA clone complemented an ATR-deficient
      bacterial mutant for Ado-B12-dependent growth on 1,2-propanediol. This
      demonstrated that the human ATR is active under physiological conditions albeit
      in a heterologous host. In addition, Western blots were used to show that ATR
      expression is altered in cell lines derived from cblB methylmalonyl aciduria
      patients compared with cell lines from normal individuals. We propose that inborn
      errors in the human ATR gene identified here result in methylmalonyl aciduria.
      The identification of genes involved in this disorder will allow improvements in
      the diagnosis and treatment of this serious disease.

PMID- 12514192
TI  - Membrane type-1 matrix metalloproteinase functions as a proprotein self
      convertase. Expression of the latent zymogen in Pichia pastoris, autolytic
      activation, and the peptide sequence of the cleavage forms.
AB  - An understanding of the regulatory mechanisms that control the activity of
      membrane type-1 matrix metalloproteinase (MT1-MMP), a key proteinase in tumor
      cell invasion, is essential for the design of potent and safe anti-cancer
      therapies. A unique proteolytic pathway regulates MT1-MMP at cancer cell
      surfaces. The abundance of proteolytic enzymes in cancer cells makes it difficult
      to identify the autocatalytic events in this pathway. To identify these events, a
      soluble form of MT1-MMP, lacking the C-terminal transmembrane and cytoplasmic
      domains, was expressed in Pichia pastoris. Following secretion, the latent
      zymogen and active enzyme were each purified from media by fast protein liquid
      chromatography. Trace amounts of active MT1-MMP induced activation of the zymogen
      and its self-proteolysis. This autocatalytic processing generated six main forms
      of MT1-MMP, each of which was subjected to the N-terminal microsequencing to
      identify the cleavage sites. Our data indicate that MT1-MMP functions as a self
      convertase and is capable of cleaving its own prodomain at the furin cleavage
      motif RRKR downward arrow Y(112), thus autocatalytically generating the mature
      MT1-MMP enzyme with an N terminus starting at Tyr(112). The mature enzyme
      undergoes further autocatalysis to the two distinct intermediates (N terminus at
      Trp(119) and at Asn(130)) and, next, to the three inactive ectodomain forms (N
      terminus at Thr(222), at Gly(284), and at Thr(299)). These findings provide, for
      the first time, a structural basis for understanding the unconventional
      mechanisms of MT1-MMP activation and regulation. Finally, our data strongly imply
      that MT1-MMP is a likely substitute for the general proprotein convertase
      activity of furin-like proteinases, especially in furin-deficient cancer cells.

PMID- 12514193
TI  - Actin-ATP hydrolysis is a major energy drain for neurons.
AB  - In cultured chick ciliary neurons, when ATP synthesis is inhibited, ATP depletion
      is reduced approximately 50% by slowing actin filament turnover with
      jasplakinolide or latrunculin A. Jasplakinolide inhibits actin disassembly, and
      latrunculin A prevents actin assembly by sequestering actin monomers.
      Cytochalasin D, which allows assembly-disassembly, but only at pointed ends, is
      less effective in conserving ATP. Ouabain, an Na(+)-K(+)-ATPase inhibitor, and
      jasplakinolide both prevent approximately 50% of the ATP loss. When applied
      together, they completely prevent ATP loss over a period of 20 min, suggesting
      that filament stabilization reduces ATP consumption by decreasing actin-ATP
      hydrolysis directly rather than indirectly by modulating the activity of Na(+)
      K(+)-ATPase, a major energy consumer.

PMID- 12514194
TI  - Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by
      orexins/hypocretins.
AB  - Orexins/hypocretins are involved in mechanisms of emotional arousal and short
      term regulation of feeding. The dense projection of orexin neurons from the
      lateral hypothalamus to mesocorticolimbic dopaminergic neurons in the ventral
      tegmental area (VTA) is likely to be important in both of these processes. We
      used single-unit extracellular and whole-cell patch-clamp recordings to examine
      the effects of orexins (A and B) and melanin-concentrating hormone (MCH) on
      neurons in this region. Orexins caused an increase in firing frequency (EC(50) 78
      nm), burst firing, or no change in firing in different groups of A10 dopamine
      neurons. Neurons showing oscillatory firing in response to orexins had smaller
      afterhyperpolarizations than the other groups of dopamine neurons. Orexins (100
      nm) also increased the firing frequency of nondopaminergic neurons in the VTA. In
      the presence of tetrodotoxin (0.5 microm), orexins depolarized both dopaminergic
      and nondopaminergic neurons, indicating a direct postsynaptic effect. Unlike the
      orexins, MCH did not affect the firing of either group of neurons. Single-cell
      PCR experiments showed that orexin receptors were expressed in both dopaminergic
      and nondopaminergic neurons and that the calcium binding protein calbindin was
      only expressed in neurons, which also expressed orexin receptors. In narcolepsy,
      in which the orexin system is disrupted, dysfunction of the orexin modulation of
      VTA neurons may be important in triggering attacks of cataplexy.

PMID- 12514195
TI  - Chronic cocaine self-administration upregulates the norepinephrine transporter
      and alters functional activity in the bed nucleus of the stria terminalis of the
      rhesus monkey.
AB  - The bed nucleus of the stria terminalis (BNST) is in a key position to influence
      the integration of motivational and visceral functions, receiving inputs from
      limbic regions, including the amygdala, and sending projections to areas central
      to reward processing, including the ventral tegmental area and nucleus accumbens.
      The BNST also possesses a high density of noradrenergic fibers. The purpose of
      the present studies was to characterize the effects of cocaine self
      administration on the regulation of norepinephrine transporter (NET) distribution
      and functional activity in the BNST of rhesus monkeys in the initial (5 d) or
      chronic (100 d) phases of cocaine self-administration. NET binding site densities
      in the BNST were assessed with quantitative in vitro receptor autoradiography
      using [(3)H]nisoxetine, and rates of local cerebral glucose utilization in the
      BNST were measured in the same monkeys using the 2-[(14)C]deoxyglucose method.
      Chronic exposure to cocaine self-administration resulted in significantly higher
      NET binding site densities (up to 52% relative to controls) throughout the BNST.
      Furthermore, cerebral metabolism was depressed significantly in a time-dependent
      manner with larger decreases after 100 d of cocaine self-administration. These
      data represent the first report of significant changes in the regulation of the
      NET resulting from cocaine exposure in primates. Furthermore, given the role of
      the BNST in cocaine withdrawal and stress-related reinstatement of self
      administration, the changes reported here may provide a substrate for these
      phenomena.

PMID- 12514196
TI  - The hippocampus plays an important role in eyeblink conditioning with a short
      trace interval in glutamate receptor subunit delta 2 mutant mice.
AB  - Mutant mice lacking the glutamate receptor subunit delta2 exhibit changes in the
      structure and function of the cerebellar cortex. The most prominent functional
      feature is a deficiency in the long-term depression (LTD) at parallel fiber
      Purkinje cell synapses. These mutant mice exhibit severe impairment during delay
      eyeblink conditioning but learn normally during trace eyeblink conditioning
      without the cerebellar LTD, even with a 0 trace interval. We investigated the
      hippocampal contribution to this cerebellar LTD-independent "0 trace interval"
      learning. The mutant mice whose dorsal hippocampi were aspirated exhibited severe
      impairment in learning, whereas those that received post-training hippocampal
      lesions retained the memory. The wild-type mice showed no impairment in either
      case. These results suggest that the hippocampal component of the eyeblink
      conditioning task becomes dominant when cerebellar LTD is impaired.

PMID- 12514197
TI  - Temporary inactivation of the bed nucleus of the stria terminalis but not of the
      amygdala blocks freezing induced by trimethylthiazoline, a component of fox
      feces.
AB  - Presentation of trimethylthiazoline (TMT, a component of fox feces) to laboratory
      rats elicits freezing, a prominent behavioral sign of anxiety or fear. The
      present study investigated the neural basis of this unlearned response. Muscimol,
      a GABA(A) receptor agonist, was injected (4.4 nmol/0.5 microl) into the bed
      nucleus of the stria terminalis (BNST) as well as into the amygdala, two brain
      areas known to be involved in anxiety and fear. Temporary inactivation of the
      BNST but not of the amygdala significantly blocked TMT-induced freezing. This
      effect was not caused by an enhancement of motor activity after BNST
      inactivation. In addition, these results confirm previous studies showing that
      freezing is possible despite amygdala inactivation. These results, and other
      findings in the literature, suggest that the BNST is critically involved in
      unlearned fear, whereas the amygdala is more involved in the acquisition and
      expression of learned fear.

PMID- 12514198
TI  - Novel therapeutic approach for the treatment of Alzheimer's disease by peripheral
      administration of agents with an affinity to beta-amyloid.
AB  - Plaques containing beta-amyloid (Abeta) peptides are one of the pathological
      features of Alzheimer's disease, and the reduction of Abeta is considered a
      primary therapeutic target. Amyloid clearance by anti-Abeta antibodies has been
      reported after immunization, and recent data have shown that the antibodies may
      act as a peripheral sink for Abeta, thus altering the periphery/brain dynamics.
      Here we show that peripheral treatment with an agent that has high affinity for
      Abeta (gelsolin or GM1) but that is unrelated to an antibody or immune modulator
      reduced the level of Abeta in the brain, most likely because of a peripherally
      acting effect. We propose that in general, compounds that sequester plasma Abeta
      could reduce or prevent brain amyloidosis, which would enable the development of
      new therapeutic agents that are not limited by the need to penetrate the brain or
      evoke an immune response.

PMID- 12514199
TI  - Quantitative single-cell differences in mu-opioid receptor mRNA distinguish
      myelinated and unmyelinated nociceptors.
AB  - A remarkable feature of opioids is that they inhibit pain that persists from
      previous injuries without eliminating either the initial pain of a new injury or
      the protective reflexes triggered by it. Here we ask whether selective expression
      of the mu-opioid receptor (MOR) gene in primary nociceptors (pain-sensing
      neurons) might contribute to this aspect of opioid specificity. We quantified
      single-cell levels of MOR mRNA and measured opioid inhibition of Ca channels on
      identified nociceptors and low-threshold mechanosensors (non-nociceptors)
      isolated from rats. Negligibly few non-nociceptors express MOR mRNA, thereby
      rendering nonpain sensations insensitive to opioids. Nearly half of nociceptors
      of all size classes also fail to express MOR mRNA or to respond to opioids. Among
      the opioid-responsive nociceptors, a gene dose-response relationship exists such
      that maximal opioid inhibition occurs when the MOR mRNA concentration of a cell
      is >15 pm. Almost all large, myelinated nociceptors express MOR mRNA below this
      level, whereas small, unmyelinated nociceptors are likely to express above it.
      Because myelinated nociceptors mediate anti-nociceptive reflexes, the data
      suggest that fine control of the MOR mRNA level contributes to a complex neural
      trait: the ability of opioids to suppress persistent pain without preventing
      response to a new injury.

PMID- 12514200
TI  - Global loss of Na,K-ATPase and its nitric oxide-mediated regulation in a
      transgenic mouse model of amyotrophic lateral sclerosis.
AB  - Na,K-ATPase plays a critical role in energy metabolism and ion fluxes. Its loss
      was investigated in the G93A mouse model of amyotrophic lateral sclerosis (ALS)
      in which the mutation of Cu/Zn superoxide dismutase (SOD1) is thought to lead to
      aberrant oxidative damage. Observed losses in spinal cord Na,K-ATPase activity
      exceeded all expectations. All three catalytic subunit isoforms (alpha1, alpha2,
      alpha3) were reduced, and the global alpha subunit loss affected not just
      neurons, glia, and myelinated axon tracts but even ependymal and pial membranes.
      Decreases in Na,K-ATPase activity were greater than losses of protein, and there
      were losses of Na,K-ATPase alpha, but not beta, subunits. Together, these
      observations are consistent with selective degradation of the alpha subunit after
      damage. Overexpression of normal SOD1 does not cause ALS-like symptoms, but it
      has other known pathological effects. In transgenic mice overexpressed normal
      human SOD1 had a smaller but still considerable effect on Na,K-ATPase.
      Furthermore, the nitric oxide-mediated regulatory pathway for Na,K-ATPase
      inhibition was undetectable in spinal cord tissue slices from mice overexpressing
      either mutant or normal human SOD1. Na,K-ATPase activity did not respond to
      nitric oxide donors, and the free radical-dependent step of the pathway could not
      be bypassed by the addition of the downstream protein kinase G activator, 8-Br
      cGMP. The data demonstrate that Na,K-ATPase is vulnerable to aberrant SOD1
      activity, making it a potential contributing factor in disease pathology.
      Moreover, the global cellular distribution of Na,K-ATPase loss indicates that
      SOD1 overexpression is far-reaching in its pathological effects.

PMID- 12514201
TI  - Synaptic plasticity in the amygdala in a model of arthritic pain: differential
      roles of metabotropic glutamate receptors 1 and 5.
AB  - Pain has a strong emotional-affective dimension, and the amygdala plays a key
      role in emotionality. Mechanisms of pain-related changes in the amygdala were
      studied at the cellular and molecular levels in a model of arthritis pain. The
      influence of the arthritic condition induced in vivo on synaptic transmission and
      group I metabotropic glutamate receptor (mGluR1 and mGluR5) function was examined
      in vitro using whole-cell voltage-clamp recordings of neurons in the central
      nucleus of the amygdala (CeA). G-protein-coupled mGluRs are implicated in various
      forms of neuroplasticity as well as in neurological and psychiatric disorders.
      Synaptic transmission was evoked by electrical stimulation of afferents from the
      basolateral amygdala (BLA) and the pontine parabrachial (PB) area in brain slices
      from control (untreated or saline-injected) rats and from arthritic rats. This
      study shows enhanced synaptic transmission of nociceptive-specific inputs (PB-
      >CeA synapse) and polymodal sensory inputs (BLA-->CeA synapse) in the arthritis
      model. CeA neurons from arthritic rats also developed increased excitability
      compared with control CeA neurons. Synaptic plasticity in the CeA was accompanied
      by increased presynaptic mGluR1 function and upregulation of mGluR1 and mGluR5. A
      selective mGluR1 antagonist reduced transmission in CeA neurons from arthritic
      animals but not in control neurons, and increased levels of mGluR1 and mGluR5
      protein were measured in the CeA of arthritic rats compared with controls. Our
      results show that plastic changes in the amygdala in an arthritis model that
      produces prolonged pain involve a critical switch of presynaptic mGluR1
      expression and function.

PMID- 12514202
TI  - Detection of calcium transients in Drosophila mushroom body neurons with camgaroo
      reporters.
AB  - Camgaroos are yellow fluorescent protein derivatives that hold promise as
      transgenically encoded calcium sensors in behaving animals. We expressed two
      versions of camgaroo in Drosophila mushroom bodies using the galactosidase-4
      (GAL4) system. Potassium depolarization of brains expressing the reporters
      produces a robust increase in fluorescence that is blocked by removing
      extracellular calcium or by antagonists of voltage-dependent calcium channels.
      The fluorescence increase is not attributable to cytoplasmic alkalization;
      depolarization induces a slight acidification of the cytoplasm of mushroom body
      neurons. Acetylcholine applied near the dendrites of the mushroom body neurons
      induces a rapid and ipsilateral-specific fluorescence increase in the mushroom
      body axons that is blocked by antagonists of calcium channels or nicotinic
      acetylcholine receptors. Fluorescence was observed to increase in all three
      classes of mushroom body neurons, indicating that all types respond to
      cholinergic innervation.

PMID- 12514203
TI  - Opposite action of beta1- and beta2-adrenergic receptors on Ca(V)1 L-channel
      current in rat adrenal chromaffin cells.
AB  - Voltage-gated Ca(2+) channels of chromaffin cells are modulated by locally
      released neurotransmitters through autoreceptor-activated G-proteins. Clear
      evidence exists in favor of a Ca(2+) channel gating inhibition mediated by
      purinergic, opioidergic, and alpha-adrenergic autoreceptors. Few and
      contradictory data suggest also a role of beta-adrenergic autoreceptors (beta
      ARs), the action of which, however, remains obscure. Here, using patch-perforated
      recordings, we show that rat chromaffin cells respond to the beta-AR agonist
      isoprenaline (ISO) by either upmodulating or downmodulating the amplitude of
      Ca(2+) currents through two distinct modulatory pathways. ISO (1 microm) could
      cause either fast inhibition (approximately 25%) or slow potentiation
      (approximately 25%), or a combination of the two actions. Both effects were
      completely prevented by propranolol. Slow potentiation was more evident in cells
      pretreated with pertussis toxin (PTX) or when beta(1)-ARs were selectively
      stimulated with ISO + ICI118,551. Potentiation was absent when the beta(2)-AR
      selective agonist zinterol (1 microm), the protein kinase A (PKA) inhibitor H89,
      or nifedipine was applied, suggesting that potentiation is associated with a PKA
      mediated phosphorylation of L-channels (approximately 40% L-current increase)
      through beta(1)-ARs. The ISO-induced inhibition was fast and reversible,
      preserved in cell treated with H89, and mimicked by zinterol. The action of
      zinterol was mostly on L-channels (38% inhibition). Zinterol action preserved the
      channel activation kinetics, the voltage-dependence of the I-V characteristic,
      and was removed by PTX, suggesting that beta(2)AR-mediated channel inhibition was
      mainly voltage independent and coupled to G(i)/G(o)-proteins. Sequential
      application of zinterol and ISO mimicked the dual action
      (inhibition/potentiation) of ISO alone. The two kinetically and pharmacologically
      distinct beta-ARs signaling uncover alternative pathways, which may serve the
      autocrine control of Ca(2+)-dependent exocytosis and other related functions of
      rat chromaffin cells.

PMID- 12514204
TI  - Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase.
AB  - We studied regulation by c-Src tyrosine kinase (Src) of KCNQ1-5 channels
      heterologously expressed in Chinese hamster ovary (CHO) cells and of native M
      current in rat sympathetic neurons. Using whole-cell patch clamp, we found that
      Src modulates currents from KCNQ3, KCNQ4, and KCNQ5 homomultimers, KCNQ2/3
      heteromultimers and native M current, but not currents from KCNQ1 or KCNQ2
      homomultimers. Src overexpression had two effects: a decrease of current
      amplitude (4- to 15-fold for cloned channels and approximately 3-fold for M
      current) and a slowing of activation kinetics by 2-fold. Both Src actions were
      mostly reversed by bath application of the Src inhibitors erbstatin (20 microm)
      and PP2 (200 nm), and mimicked by the tyrosine phosphatase inhibitor sodium
      vanadate (100 microm). Immunoprecipitation and immunoblot analysis showed Src
      dependent phosphotyrosine signals associated with KCNQ3, KCNQ4, and KCNQ5 but not
      with KCNQ1 or KCNQ2 that may be tyrosine phosphorylation of the channel subunits.
      Expression of a dominant negative Src that cannot phosphorylate substrates had no
      effect on the current and did not induce phosphotyrosine signals associated with
      KCNQ3-5 subunits, further indicating that Src actions on KCNQ currents are
      mediated by tyrosine phosphorylation. Immunostaining and confocal analysis showed
      no effect of Src overexpression on the abundance of KCNQ3 protein in CHO cells.
      Finally, experiments using cloned KCNQ2/3 channels, Src and M(1) muscarinic
      receptors, and sympathetic neurons demonstrated that the actions on KCNQ channels
      by Src and by muscarinic agonists use distinct mechanisms.

PMID- 12514205
TI  - Synaptic interactions of late-spiking neocortical neurons in layer 1.
AB  - Layer 1 of the neocortex is an important zone in which synaptic integration of
      inputs originating from a variety of cerebral regions is thought to take place.
      Layer 1 does not contain pyramidal cells, and several histochemical studies have
      suggested that most layer 1 neurons are GABAergic. However, although layer 1
      neurons could be an important source of inhibition in this layer, the synaptic
      action of these neurons and the identity of their postsynaptic targets are
      unknown. We studied the physiological properties and synaptic interactions of a
      class of cells within layer 1 called late-spiking (LS) cells. The dendrites and
      axons of layer 1 LS cells were confined primarily to layer 1. Using paired
      recording, we showed that LS cells formed GABAergic connections with other LS
      cells as well as with non-LS cells in layer 1 and with pyramidal cells in layer
      2/3. We also found that layer 2/3 pyramidal neurons provide excitatory inputs to
      LS cells. It has been suggested previously that GABAergic neurons belonging to
      the same class in the cortex are electrically coupled. In agreement with that
      hypothesis, we found that LS cells were interconnected by electrical coupling
      (83%), whereas electrical coupling between LS cells and non-LS cells was
      infrequent (2%). Thus, we provide evidence showing that a group of GABAergic
      neurons within layer 1 are specifically interconnected by electrical coupling and
      can provide significant inhibitory inputs to neurons in layer 1 and to distal
      dendrites of pyramidal cells.

PMID- 12514206
TI  - Local and global spontaneous calcium events regulate neurite outgrowth and onset
      of GABAergic phenotype during neural precursor differentiation.
AB  - Neural stem cells can generate in vitro progenitors of the three main cell
      lineages found in the CNS. The signaling pathways underlying the acquisition of
      differentiated phenotypes in these cells are poorly understood. Here we tested
      the hypothesis that Ca(2+) signaling controls differentiation of neural
      precursors. We found low-frequency global and local Ca(2+) transients occurring
      predominantly during early stages of differentiation. Spontaneous Ca(2+) signals
      in individual precursors were not synchronized with Ca(2+) transients in
      surrounding cells. Experimentally induced changes in the frequency of local
      Ca(2+) signals and global Ca(2+) rises correlated positively with neurite
      outgrowth and the onset of GABAergic neurotransmitter phenotype, respectively.
      NMDA receptor activity was critical for alterations in neuronal morphology but
      not for the timing of the acquisition of the neurotransmitter phenotype. Thus,
      spontaneous Ca(2+) signals are an intrinsic property of differentiating
      neurosphere-derived precursors. Their frequency may specify neuronal morphology
      and acquisition of neurotransmitter phenotype.

PMID- 12514207
TI  - Differential effects of short- and long-term potentiation on cell firing in the
      CA1 region of the hippocampus.
AB  - Long-term potentiation (LTP) in the hippocampus enhances the ability of a
      stimulus to produce cell firing, not only by increasing the strength of the
      EPSPs, but also by increasing the efficiency of the input/output (I/O) function
      of pyramidal neurons. This means that EPSPs of a given size more easily elicit
      spikes after LTP, a process known as EPSP-spike (E-S) potentiation. In contrast
      to LTP, it is not known whether the synaptic strengthening produced by paired
      pulse facilitation (PPF) also results in changes in the I/O function. We have
      addressed this question by examining E-S curves from rat hippocampal area CA1 in
      response to both PPF and LTP. We describe a novel form of I/O modulation in which
      PPF produces E-S depression; that is, the E-S curve is shifted to the right,
      indicating a decreased ability of EPSPs to elicit action potentials. Consistent
      with the notion that E-S potentiation observed with LTP is caused by long-term
      increases in the excitatory-inhibitory ratio, we show that PPF-induced E-S
      depression relies on short-term decreases in this ratio. These results indicate
      that different forms of synaptic plasticity that produce the same degree of EPSP
      potentiation can result in dramatically different effects on cell firing, because
      of the dynamic changes in the excitatory-inhibitory balance within local
      circuits.

PMID- 12514208
TI  - Distinct functional roles of the metabotropic glutamate receptors 1 and 5 in the
      rat globus pallidus.
AB  - Group I metabotropic glutamate receptors (mGluRs) 1 and 5 frequently colocalize
      in the same neurons throughout the CNS. Because both receptors can couple to the
      same effector systems, the purpose of their cellular coexpression remains
      unclear. Here, we report that group I mGluR1 and mGluR5 have distinct functional
      roles in type II neurons of the rat globus pallidus (GP). Type II GP neurons form
      a large population of GABAergic projection neurons that are characterized by the
      presence of inwardly rectifying current I(h), low-threshold voltage-activated
      calcium current I(t), and activity at rest. Although immunocytochemical analysis
      reveals a high degree of neuronal colocalization of the two group I mGluRs in the
      GP, activation of mGluR1 only directly depolarizes type II GP neurons.
      Interestingly, blockade of mGluR5 by a highly selective antagonist,
      methylphenylethynylpyridine, leads to the potentiation of the mGluR1-mediated
      depolarization in this neuronal subpopulation. Metabotropic GluR1 desensitizes
      during repeated activation with the agonist in type II GP neurons, and blocking
      mGluR5 prevents the desensitization of the mGluR1-mediated depolarization.
      Elimination of the activity of protein kinase C (PKC) by an application of 1
      microm bisendolylmaleimide or 1 microm chelerythrine, both protein kinase C
      inhibitors, potentiates the mGluR1-mediated response and prevents the
      desensitization of mGluR1 in type II GP neurons, suggesting that the effect of
      mGluR5 on mGluR1 signaling may involve PKC. Together, these data illustrate a
      novel mechanism by which mGluR1 and mGluR5, members of the same family of G
      protein-coupled receptors, can interact to modulate neuronal activity in the rat
      GP.

PMID- 12514209
TI  - KIF17 dynamics and regulation of NR2B trafficking in hippocampal neurons.
AB  - KIF17, a recently characterized member of the kinesin superfamily proteins, has
      been proposed to bind in vitro to a protein complex containing mLin10 (Mint1/X11)
      and the NR2B subunit of the NMDA receptors (NMDARs). In the mammalian brain,
      NMDARs play an important role in synaptic plasticity, learning, and memory. Here
      we present, for the first time, the dynamic properties of KIF17 and provide
      evidence of its function in the transport of NR2B in living mammalian neurons.
      KIF17 vesicles enter and move specifically along dendrites in a processive way,
      at an average speed of 0.76 microm/sec. These vesicles are effectively associated
      with extrasynaptic NR2B, and thus they transport and deliver NR2B subunits in
      dendrites. However, KIF17 does not seem to enter directly into postsynaptic
      regions. Cellular knockdown or functional blockade of KIF17 significantly impairs
      NR2B expression and its synaptic localization. Interestingly, the decrease in the
      number of synaptic NR2B subunits is followed by a parallel increase in the number
      of NR2A subunits at synapses. In contrast, upregulation of the expression level
      of NR2B, after treatment with the NMDAR antagonist D(-)-2-amino-5
      phosphonopentanoic acid, simultaneously increases the expression level of KIF17.
      These observations concerning the downregulation or upregulation of KIF17 and
      NR2B reveal the probable existence of a shared regulation process between the
      motor and its cargo. Taken together, these results illustrate the complex
      mechanisms underlying the active transport and regulation of NR2B by the
      molecular motor KIF17 in living hippocampal neurons.

PMID- 12514210
TI  - Trophic restoration of the nigrostriatal dopaminergic pathway in long-term
      carotid body-grafted parkinsonian rats.
AB  - We studied the mechanisms underlying long-term functional recovery of
      hemiparkinsonian rats grafted intrastriatally with carotid body (CB) cell
      aggregates. Amelioration of their motor syndrome is a result of the trophic
      actions of these grafts on the remaining ipsilateral substantia nigra neurons
      rather than of the release of dopamine from the CB grafts. The grafts maintain a
      stable morphological appearance and differentiated cell phenotype for the
      duration of the life of the host. Adult CB expresses high levels of glial cell
      line-derived neurotrophic factor (GDNF) and the multicomponent GDNF receptor
      complex. These properties may contribute to the trophic actions of the CB
      transplants on nigrostriatal neurons and to their extraordinary longevity. We
      show that CB glomus cells, although highly dopaminergic, are protected from
      dopamine-mediated oxidative damage because of the absence of the high-affinity
      dopamine transporter. Thus, intrastriatal CB grafts are uniquely suited for long
      term delivery of trophic factors capable of promoting restoration of the
      nigrostriatal pathway.

PMID- 12514211
TI  - Two intracellular pathways mediate metabotropic glutamate receptor-induced Ca2+
      mobilization in dopamine neurons.
AB  - Activation of metabotropic glutamate receptors (mGluRs) causes membrane
      hyperpolarization in midbrain dopamine neurons. This hyperpolarization results
      from the opening of Ca(2+)-sensitive K(+) channels, which is mediated by the
      release of Ca(2+) from intracellular stores. Neurotransmitter-induced
      mobilization of Ca(2+) is generally ascribed to the action of inositol 1,4,5
      triphosphate (IP(3)) in neurons. Here we show that the mGluR-mediated Ca(2+)
      mobilization in dopamine neurons is caused by two intracellular second
      messengers: IP(3) and cyclic ADP-ribose (cADPR). Focal activation of mGluRs,
      attained by synaptic release of glutamate or iontophoretic application of
      aspartate, induced a wave of Ca(2+) that spread over a distance of approximately
      50 microm through dendrites and the soma. Simultaneous inhibition of both IP(3)-
      and cADPR-dependent pathways with heparin and 8-NH(2)-cADPR was required to block
      the mGluR-induced Ca(2+) release, indicating a redundancy in the signaling
      mechanism. Activation of ryanodine receptors was suggested to mediate the cADPR
      dependent pathway, because ruthenium red, an antagonist of ryanodine receptors,
      inhibited the mGluR response only when the cADPR-dependent pathway was isolated
      by blocking the IP(3)-dependent pathway with heparin. Finally, the mGluR-mediated
      hyperpolarization was shown to induce a transient pause in the spontaneous firing
      of dopamine neurons. These results demonstrate that an excitatory
      neurotransmitter glutamate uses multiple intracellular pathways to exert an
      inhibitory control on the excitability of dopamine neurons.

PMID- 12514212
TI  - Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain.
AB  - The underlying mechanisms of neuropathic pain are poorly understood, and existing
      treatments are mostly ineffective. We recently demonstrated that antisense
      mediated "knock-down" of the sodium channel isoform, Na(V)1.8, reverses
      neuropathic pain behavior after L5/L6 spinal nerve ligation (SNL), implicating a
      critical functional role of Na(V)1.8 in the neuropathic state. Here we have
      investigated mechanisms through which Na(V)1.8 contributes to the expression of
      experimental neuropathic pain. Na(V)1.8 does not appear to contribute to
      neuropathic pain through an action in injured afferents because the channel is
      functionally downregulated in the cell bodies of injured neurons and does not
      redistribute to injured terminals. Although there was little change in Na(V)1.8
      protein or functional channels in the cell bodies of uninjured neurons in L4
      ganglia, there was a striking increase in Na(V)1.8 immunoreactivity along the
      sciatic nerve. The distribution of Na(V)1.8 reflected predominantly the presence
      of functional channels in unmyelinated axons. The C-fiber component of the
      sciatic nerve compound action potential (CAP) was resistant (>40%) to 100 microm
      TTX after SNL, whereas both A- and C-fiber components of sciatic nerve CAP were
      blocked (>90%) by 100 microm TTX in sham-operated rats or the contralateral
      sciatic nerve of SNL rats. Attenuating expression of Na(V)1.8 with antisense
      oligodeoxynucleotides prevented the redistribution of Na(V)1.8 in the sciatic
      nerve and reversed neuropathic pain. These observations suggest that aberrant
      activity in uninjured C-fibers is a necessary component of pain associated with
      partial nerve injury. They also suggest that blocking Na(V)1.8 would be an
      effective treatment of neuropathic pain.

PMID- 12514213
TI  - Identification of two distinct progenitor populations in the lateral ganglionic
      eminence: implications for striatal and olfactory bulb neurogenesis.
AB  - The lateral ganglionic eminence (LGE) is known to give rise to striatal
      projection neurons as well as interneurons, which migrate in the rostral
      migratory stream (RMS) to populate the granule cell and glomerular layers of the
      olfactory bulb. Because all of these neuronal subtypes express Distalless-related
      (DLX) homeobox proteins during their differentiation, we set out to further
      characterize progenitors in the Dlx-positive domain of the LGE. Previous studies
      have shown that the LIM homeobox protein Islet1 (ISL1) marks the LGE
      subventricular zone (SVZ) and differentiating striatal projection neurons.
      However, ISL1 is not expressed in neurons of the developing olfactory bulb or the
      RMS. We show here that the dorsal-most portion of the Dlx-expressing region of
      the LGE SVZ lacks ISL1 cells. This dorsal domain, however, contains cells that
      express the ETS transcription factor Er81, which is also expressed in granule and
      periglomerular cells of the developing and adult olfactory bulb. Moreover, the
      adult SVZ and RMS contain numerous Er81-positive cells. Fate-mapping studies
      using Dlx5/6-cre transgenic mice demonstrate that Er81-positive cells in the
      granule cell and glomerular layers of the olfactory bulb derive from the Dlx
      expressing SVZ region. These findings suggest that the LGE SVZ contains two
      distinct progenitor populations: a DLX(+);ISL1(+) population representing
      striatal progenitors and a DLX(+);Er81(+) population comprising olfactory bulb
      interneuron progenitors. In support of this, mice mutant for the homeobox genes
      Gsh2 and Gsh1/2, which show olfactory bulb defects, exhibit dramatically reduced
      numbers of Er81-positive cells in the LGE SVZ as well as in the olfactory bulb
      mantle.

PMID- 12514214
TI  - Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth
      cone collapse.
AB  - The NG2 chondroitin sulfate proteoglycan, an integral membrane proteoglycan,
      inhibits axon growth from cerebellar granule neurons and dorsal root ganglia
      (DRG) neurons in vitro. The extracellular domain of the NG2 core protein contains
      three subdomains: an N-terminal globular domain (domain 1), a central extended
      domain that has the sites for glycosaminoglycan (GAG) attachment (domain 2), and
      a juxtamembrane domain (domain 3). Here, we used domain-specific fusion proteins
      and antibodies to map the inhibitory activity within the NG2 core protein. Fusion
      proteins encoding domain 1 (D1-Fc) or domain 3 (D3-Fc) of NG2 inhibited axon
      growth from cerebellar granule neurons when the proteins were substrate-bound.
      These proteins also induced growth cone collapse from newborn DRG neurons when
      added to the culture medium. Domain 2 only inhibited axon growth when the GAG
      chains were present. Neutralizing antibodies directed against domain 1 or 3
      blocked completely the inhibition from substrates coated with D1-Fc or D3-Fc.
      When the entire extracellular domain of NG2 was used as a substrate, however,
      both neutralizing antibodies were needed to reverse completely the inhibition.
      When NG2 was expressed on the surface of HEK293 cells, the neutralizing anti-D1
      antibody was sufficient to block the inhibition, whereas the anti-D3 antibody had
      no effect. These results suggest that domains 1 and 3 of NG2 can inhibit neurite
      growth independently. These inhibitory domains may be differentially exposed
      depending on whether NG2 is presented as an integral membrane protein or as a
      secreted protein associated with the extracellular matrix.

PMID- 12514215
TI  - Genetic modulation of tau phosphorylation in the mouse.
AB  - The axonal microtubule stabilizing protein tau is hyperphosphorylated in several
      neurodegenerative conditions, including Alzheimer's disease, yet the genes that
      regulate tau phosphorylation are largely unknown. Disabled-1 (Dab1) is a
      cytoplasmic adapter protein that interacts with apolipoprotein E (ApoE) receptors
      and controls neuronal positioning during embryonic brain development. We have
      investigated the role of Dab1 in tau phosphorylation. We found that wild-type
      Dab1, but not a mutant lacking tyrosine phosphorylation sites, protects mice from
      the hyperphosphorylation of tau. However, the absence of Dab1 is not sufficient
      to cause tau hyperphosphorylation, because hyperphosphorylation is manifested
      only when Dab1 is mutated in specific mouse strain backgrounds. Tau
      hyperphosphorylation correlates with early death in susceptible mouse strains,
      and it occurs in the neurons of the hippocampus and dentate gyrus. By
      quantitative trait locus (QTL) analysis of Dab1-deficient mice on a hybrid strain
      background, we uncovered one significant and three suggestive chromosomal loci
      that modulate tau phosphorylation. Two of these QTL regions contain genes that
      are defective in early onset Alzheimer's disease. Our findings suggest that Dab1
      gene disruption sensitizes mice to tau hyperphosphorylation contingent on
      specific haplotypes that are linked to Alzheimer's disease loci. Dab1 mutant mice
      provide an animal model for studying the relationships between ApoE receptors,
      tau hyperphosphorylation, and Alzheimer's disease.

PMID- 12514216
TI  - Gradient steepness influences the pathfinding decisions of neuronal growth cones
      in vivo.
AB  - Gradients of chemotropic molecules are generally thought to be fundamental for
      the guidance of neuronal growth cones in the developing embryo. Here we show that
      the grasshopper-secreted semaphorin Sema 2a is expressed in a gradient during the
      period of tibial Ti1 pioneer axon pathfinding into the CNS. At two critical Ti1
      growth cone choice points, the Sema 2a gradient differs in steepness, whereas the
      absolute concentration is the same. Although Ti1 growth cones enter and extend up
      both steep and shallow gradients of Sema 2a, fewer projection errors occur along
      the steep gradient, suggesting that the steepness of the gradient encodes the
      critical guidance information into the pathfinding growth cone. In contrast, an
      increase in the absolute concentration of Sema 2a appears to constrain the Ti1
      growth cone size. Using these in vivo gradients, we provide evidence that the Ti1
      growth cone detects the Sema 2a gradient by measuring the fractional change in
      Sema 2a concentration, thereby demonstrating one mechanism that neuronal growth
      cones may use to detect and read gradients in vivo.

PMID- 12514217
TI  - Abnormal development of forebrain midline glia and commissural projections in
      Nfia knock-out mice.
AB  - Nuclear factor I (NFI) genes are expressed in multiple organs throughout
      development (Chaudhry et al., 1997; for review, see Gronostajski, 2000). All four
      NFI genes are expressed in embryonic mouse brain, with Nfia, Nfib, and Nfix being
      expressed highly in developing cortex (Chaudhry et al., 1997). Disruption of the
      Nfia gene causes agenesis of the corpus callosum (ACC), hydrocephalus, and
      reduced GFAP expression (das Neves et al., 1999). Three midline structures, the
      glial wedge, glia within the indusium griseum, and the glial sling are involved
      in development of the corpus callosum (Silver et al., 1982; Silver and Ogawa,
      1983; Shu and Richards, 2001). Because Nfia(-)/- mice show glial abnormalities
      and ACC, we asked whether defects in midline glial structures occur in Nfia(-)/-
      mice. NFI-A protein is expressed in all three midline populations. In Nfia(-)/-,
      mice sling cells are generated but migrate abnormally into the septum and do not
      form a sling. Glia within the indusium griseum and the glial wedge are greatly
      reduced or absent and consequently Slit2 expression is also reduced. Although
      callosal axons approach the midline, they fail to cross and extend aberrantly
      into the septum. The hippocampal commissure is absent or reduced, whereas the
      ipsilaterally projecting perforating axons (Hankin and Silver, 1988; Shu et al.,
      2001) appear relatively normal. These results support an essential role for
      midline glia in callosum development and a role for Nfia in the formation of
      midline glial structures.

PMID- 12514218
TI  - SRC-1 null mice exhibit moderate motor dysfunction and delayed development of
      cerebellar Purkinje cells.
AB  - Hormones and nuclear receptors (NRs) play important roles in brain development
      and function. The recently identified steroid receptor coactivator (SRC) family
      contains three homologous members that can enhance transcriptional activities of
      NRs and certain non-NR transcription factors. To study the role of SRC-1 in brain
      development and function, we examined the spatial and temporal expression
      patterns of SRC-1 and characterized the phenotypes of brain development and
      function in SRC-1 knock-out (SRC-1(-)/-) mice. In the adult mouse brain, SRC-1 is
      highly expressed in the olfactory bulb, hippocampus, piriform cortex, amygdala,
      hypothalamus, cerebellum, and brainstem. Multiple behavioral tests revealed that
      SRC-1(-)/- mice exhibit normal hippocampal function but moderate motor
      dysfunction. The behavior phenotypes correlate with the spatial distribution of
      the SRC family members. In most brain structures where SRC-1 is expressed, SRC-2
      is expressed at lower levels; however, SRC-3 mRNA is detectable only in the
      hippocampus. In the adult cerebellum, Purkinje cells (PCs) preferentially express
      SRC-1 over SRC-2, but SRC-2 mRNA is slightly elevated in the SRC-1(-)/- PCs.
      During embryonic development, SRC-1 is expressed in the cerebellar primordium.
      SRC-2 is expressed in PCs after postnatal day (P) 10. Time course analysis
      revealed that the precursors of SRC-1(-)/- PCs were generated approximately 2 d
      later than wild-type precursor cells. A further delay in SRC-1(-)/- PC maturation
      was detected at the neonatal stage. The morphology and number of SRC-1(-)/- PCs
      were equivalent to wild type by P10; this timing correlated with the early
      expression of SRC-2 in the SRC-1(-)/- PCs. These results demonstrate that the
      relative levels of SRC expression are region specific, and the degree of
      overlapping expression may influence their functional redundancy. Disruption of
      SRC-1 specifically delays the PC development and maturation in early stages and
      results in moderate motor dysfunction in adulthood.

PMID- 12514219
TI  - Expression of inducible nitric oxide synthase after focal cerebral ischemia
      stimulates neurogenesis in the adult rodent dentate gyrus.
AB  - The generation of new neurons in the adult mammalian hippocampus is thought to
      play a role in repairing the brain after injury. Here, we show that 7 d after
      focal cerebral ischemia, newly divided cells in the dentate gyrus of adult rats
      increased to approximately sevenfold, compared with sham controls. In the same
      area, this enhanced dentate neurogenesis was associated with activation of
      inducible nitric oxide synthase (iNOS). Inhibition of iNOS by aminoguanidine
      prevented ischemia-induced neurogenesis in the dentate gyrus. In null mutant mice
      lacking the iNOS gene, increased neurogenesis was not observed after focal
      cerebral ischemia. This study demonstrates that expression of iNOS is necessary
      for ischemia-stimulated cell birth in the dentate gyrus and indicates that
      activation of iNOS may provide a possible strategy for functional recovery from
      cerebral ischemic insult.

PMID- 12514220
TI  - Normal female sexual development requires neuregulin-erbB receptor signaling in
      hypothalamic astrocytes.
AB  - The initiation of mammalian puberty requires the activation of hypothalamic
      neurons secreting the neuropeptide luteinizing hormone-releasing hormone (LHRH).
      It is thought that this activation is caused by changes in trans-synaptic input
      to LHRH neurons. More recently, it has been postulated that the pubertal increase
      in LHRH secretion in female animals also requires neuron-glia signaling mediated
      by growth factors of the epidermal growth factor (EGF) family and their
      astrocytic erbB receptors. Although it appears clear that functional astrocytic
      erbB1 receptors are necessary for the timely advent of puberty, the physiological
      contribution that erbB4 receptors may make to this process has not been
      established. To address this issue, we generated transgenic mice expressing a
      dominant-negative erbB4 receptor (DN-erbB4) under the control of the GFAP
      promoter, which targets transgene expression to astrocytes. DN-erbB4 expression
      is most abundant in hypothalamic astrocytes, where it blocks the ligand-dependent
      activation of glial erbB4 and erbB2 receptors, without affecting erbB1 (EGF)
      receptor signaling. Mice carrying the transgene exhibit delayed sexual maturation
      and a diminished reproductive capacity in early adulthood. These abnormalities
      are related to a deficiency in pituitary gonadotropin hormone secretion, caused
      by impaired release of LHRH, the hypothalamic neuropeptide that controls sexual
      development. In turn, the reduction in LHRH release is caused by the inability of
      hypothalamic astrocytes to respond to neuregulin (NRG) with production of
      prostaglandin E(2), which in wild-type animals mediates the stimulatory effect of
      astroglial erbB receptor activation on neuronal LHRH release. Thus, neuron
      astroglia communication via NRG-erbB4/2 receptor signaling appears to be
      essential for the timely unfolding of the developmental program by which the
      brain controls mammalian sexual maturation.

PMID- 12514221
TI  - Prospective cell sorting of embryonic rat neural stem cells and neuronal and
      glial progenitors reveals selective effects of basic fibroblast growth factor and
      epidermal growth factor on self-renewal and differentiation.
AB  - We directly isolated neural stem cells and lineage-restricted neuronal and glial
      progenitors from the embryonic rat telencephalon using a novel strategy of
      surface labeling and fluorescence-activated cell sorting. Neural stem cells,
      which did not express surface epitopes characteristic of differentiation or
      apoptosis, were sorted by negative selection. These cells predominantly expressed
      fibroblast growth factor receptor type 1 (FGFR-1), and a minority exhibited basic
      fibroblast growth factor (bFGF), whereas few expressed epidermal growth factor
      receptor (EGFR) or EGF. Clonal analyses revealed that these cells primarily self
      renewed without differentiating in bFGF-containing medium, whereas few survived
      or expanded in EGF-containing medium. Culturing of neural stem cells in bFGF- and
      EGF-containing medium permitted both self-renewal and differentiation into
      neuronal, astroglial, and oligodendroglial phenotypes. In contrast, lineage
      restricted progenitors were directly sorted by positive selection using a
      combination of surface epitopes identifying neuronal or glial phenotypes or both.
      These cells were also primarily FGFR-1(+), with few EGFR(+), and most expanded
      and progressed along their expected lineages in bFGF-containing medium but not in
      EGF-containing medium. Ca(2+) imaging of self-renewing neural stem cells cultured
      in bFGF-containing medium revealed that bFGF, but not EGF, induced cytosolic
      Ca(2+) (Ca(2+)c) responses in these cells, whereas in bFGF- and EGF-containing
      medium, both bFGF and EGF evoked Ca(2+)c signals only in differentiating progeny
      of these cells. The results demonstrate that bFGF, but not EGF, sustains a
      calcium-dependent self-renewal of neural stem cells and early expansion of
      lineage-restricted progenitors, whereas together the two growth factors permit
      the initial commitment of neural stem cells into neuronal and glial phenotypes.

PMID- 12514222
TI  - DARP-36aa selectively promotes survival and morphological development of cultured
      mesencephalic neurons.
AB  - We examined the effects of DARP-36aa on the survival and morphological
      development of embryonic rat mesencephalic neurons. Treatment of mesencephalic
      cultures with DARP-36aa, a synthetic peptide corresponding to the N terminal of
      dopamine-releasing protein (DARP), resulted in a 1.8-fold increase in neuron
      survival. Morphological analysis revealed that DARP-36aa-treated neurons
      contained 48% more branching points per neuron compared with controls. DARP-36aa
      selectively affected mesencephalic cultures; diencephalic and C6 glioma cells
      were not affected by DARP-36aa treatments. Mesencephalic cultures were also
      incubated with polyclonal antibodies against DARP-36aa (anti-DARP-36aa) to assess
      the effect of immunoneutralization of endogenous DARP on these cells.
      Mesencephalic cultures treated with anti-DARP-36aa contained 43% fewer neurons,
      and the number of branching points per neuron was decreased by nearly twofold
      compared with cultures grown with medium alone. Similar to cultures treated with
      DARP-36aa, immunoneutralization of DARP had no effect on any parameters examined
      in primary diencephalic and C6 glioma cultures. Mesencephalic cultures maintained
      in the presence of DARP-36aa had a 3.2-fold increase in the number of tyrosine
      hydroxylase (TH)-immunoreactive neurons, whereas anti-DARP-36aa incubations
      decreased TH-immunoreactive neurons by 40% compared with control cultures.
      Finally, coincubation of the specific tyrosine kinase inhibitor genistein with
      DARP-36aa resulted in a complete attenuation of DARP-36aa-mediated neuron
      survival and development in mesencephalic cultures. The findings indicate that
      DARP-36aa is a novel neurotrophic peptide that selectively promotes the survival
      and development of mesencephalic neurons.

PMID- 12514223
TI  - Signaling by bone morphogenetic proteins and Smad1 modulates the postnatal
      differentiation of cerebellar cells.
AB  - Previous studies have demonstrated that bone morphogenetic proteins (BMPs)
      activate the Smad1 signaling pathway to regulate cell determination and
      differentiation in the embryonic nervous system. Studies examining gene and
      protein expression in the rat cerebellum suggest that this pathway also regulates
      postnatal differentiation. Using microarrays, we found that Smad1 mRNA expression
      in the cerebellum increases transiently at postnatal day 6 (P6).
      Immunohistochemistry and Western blots showed that Smad1 and BMP4 proteins are
      present in the cerebellum, and that their expression also changes postnatally.
      The proteins are detectable at P4-P6, a stage at which most cerebellar cells
      reside in the external germinal layer (EGL), where they extensively
      differentiate. The levels become maximal at P8-P10, when neurons begin to migrate
      from the EGL into their mature positions in the internal granule layer. In
      cerebellar cultures prepared at P6 or P10, BMP4 activates Smad1 signaling to
      modulate cell differentiation. Brief BMP4 application caused Smad1 translocation
      from the neuronal cytoplasm into the nucleus, where it is known to regulate
      transcription in association with Smad4. Longer BMP4 treatment promoted the
      differentiation of both neuronal and non-neuronal cells. By 3 d, neuronal
      processes appeared more fasciculated, and the level of synaptotagmin, a protein
      found in synaptic vesicles, increased. In addition, many astroglial cells became
      more branched and stellate in morphology. The BMP-induced changes were reduced by
      treatment with antisense oligonucleotides to Smad1 or Smad4. These findings in
      vivo and in culture suggest that BMP4 and Smad1 signaling participate in
      regulating postnatal cerebellar differentiation.

PMID- 12514224
TI  - Hydrogen peroxide modulation of synaptic plasticity.
AB  - Unlike the proposed role of reactive oxygen species in neurodegeneration, acute
      effects of reactive oxygen on synaptic plasticity are poorly understood. Using
      rat hippocampal slices, we found that exposure to a high concentration (0.5-5 mm)
      of H(2)O(2) reduces EPSPs in both potentiated and nonpotentiated synapses.
      Exposure of the slices to 20 microm H(2)O(2) did not affect expression of
      preestablished long-term potentiation (LTP) but prevented induction of new LTP
      and enhanced long-term depression (LTD). Surprisingly, 1 microm H(2)O(2) caused a
      twofold increase in LTP compared with controls, and it further enhanced NMDA
      independent LTP. A low concentration of H(2)O(2) also suppressed LTD. Nifedipine,
      an L-type calcium channel blocker, did not affect control LTP but blocked effects
      of both 1 and 20 microm H(2)O(2). Calcineurin inhibitors [FK506 (FR900506) and
      cyclosporin A but not rapamycin] acted similarly and also restored LTP in the
      presence of 20 microm H(2)O(2). These results suggest that H(2)O(2) alters NMDA
      independent, voltage-gated calcium channel-mediated LTP by activating
      calcineurin.

PMID- 12514225
TI  - The C264Y missense mutation in the extracellular domain of L1 impairs protein
      trafficking in vitro and in vivo.
AB  - The neural cell adhesion molecule L1, a member of the immunoglobulin superfamily,
      performs important functions in the developing and adult nervous system and is
      implicated in neuronal migration and survival, elongation, fasciculation and
      pathfinding of axons, and synaptic plasticity. This view is in line with the fact
      that mutations in the L1 gene result in severe neurological syndromes in humans.
      Patients with missense mutations in the extracellular domain of L1 often develop
      severe phenotypes. Here, we characterized in vitro and in vivo the missense
      mutation C264Y, which is located in the extracellular domain of L1 and causes a
      severe phenotype in humans. Transfection studies in vitro demonstrate that L1
      carrying this missense mutation is not expressed at the cell surface but instead
      is located intracellularly, most likely within the endoplasmic reticulum. Lack of
      cell surface expression of L1 with a C264Y mutation was confirmed in a transgenic
      mouse line expressing the C264Y mutation under the control of the L1 promoter in
      an L1-deficient background. Analysis of these transgenic mice indicates that they
      represent functional null mutants, phenotypically indistinguishable from L1
      deficient mice. These observations corroborate the view that impaired cell
      surface expression of mutated variants of L1 is a potential explanation for the
      high number of severe pathogenic mutations identified within the human L1 gene.

PMID- 12514226
TI  - Provision of brain-derived neurotrophic factor via anterograde transport from the
      eye preserves the physiological responses of axotomized geniculate neurons.
AB  - The neurotrophic factors of the nerve growth factor family (neurotrophins) have
      been shown to promote neuronal survival after brain injury and in various models
      of neurodegenerative conditions. However, it has not been determined whether
      neurotrophin treatment results in the maintenance of function of the rescued
      cells. Here we have used the retrograde degeneration of geniculate neurons as a
      model system to evaluate neuronal rescue and sparing of function after
      administration of brain-derived neurotrophic factor (BDNF). Death of geniculate
      neurons was induced by a visual cortex lesion in adult rats, and exogenous BDNF
      was delivered to the axotomized geniculate cells via anterograde transport after
      injection into the eye. By microelectrode recordings from the geniculate in vivo
      we have measured several physiological parameters such as contrast threshold,
      spatial resolution (visual acuity), signal-to-noise ratio, temporal resolution,
      and response latency. In control lesioned animals we found that geniculate cell
      dysfunction precedes the onset of neuronal death, indicating that an assessment
      of neuronal number per se is not predictive of functional performance. The
      administration of BDNF resulted in a highly significant cell-saving effect up to
      2 weeks after the cortical damage and maintained nearly normal physiological
      responses in the geniculate. This preservation of function in adult axotomized
      neurons suggests possible therapeutic applications of BDNF.

PMID- 12514227
TI  - Maternal influenza infection causes marked behavioral and pharmacological changes
      in the offspring.
AB  - Maternal viral infection is known to increase the risk for schizophrenia and
      autism in the offspring. Using this observation in an animal model, we find that
      respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the
      human influenza virus yields offspring that display highly abnormal behavioral
      responses as adults. As in schizophrenia and autism, these offspring display
      deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared
      with control mice, the infected mice also display striking responses to the acute
      administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic
      (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in
      both open-field and novel-object tests, and they are deficient in social
      interaction. At least some of these behavioral changes likely are attributable to
      the maternal immune response itself. That is, maternal injection of the synthetic
      double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the
      offspring in the absence of virus. Therefore, maternal viral infection has a
      profound effect on the behavior of adult offspring, probably via an effect of the
      maternal immune response on the fetus.

PMID- 12514228
TI  - Differential response patterns in the striatum and orbitofrontal cortex to
      financial reward in humans: a parametric functional magnetic resonance imaging
      study.
AB  - Responses to monetary reward in humans have been assessed in a number of recent
      functional imaging studies, and it is clear that the neuronal substrates of
      financial reinforcement overlap extensively with regions responding to primary
      reinforcers, such as food. Money has the practical advantage of being an
      objectively quantifiable reinforcer. In this study, we exploit this advantage
      using a parametric functional magnetic resonance imaging design to look at the
      patterns of responding to systematically varying reward values. Twelve healthy
      volunteers were scanned during performance of a rewarded target detection task,
      in which the reward value varied between task blocks. We observed three distinct
      patterns of responding in different regions. Amygdala, striatum, and dopaminergic
      midbrain responded to the presence of rewards, regardless of value. In contrast,
      premotor cortex showed a linear increase in response with increasing reward
      value. Finally, medial and lateral foci of orbitofrontal cortex responded
      nonlinearly, such that response was enhanced for the lowest and highest reward
      values relative to the midrange. These results suggest functional distinction in
      response patterns within a distributed reward system.

PMID- 12514229
TI  - Functional subregions in primary auditory cortex defined by thalamocortical
      terminal arbors: an electrophysiological and anterograde labeling study.
AB  - Several functional maps have been described in primary auditory cortex, including
      those related to frequency, tuning, latency, binaurality, and intensity. Many of
      these maps are arranged in a discontinuous or patchy manner. Similarly,
      thalamocortical projections arising from the ventral division of the medial
      geniculate body to the primary auditory cortex are also patchy. We used
      anterograde labeling and electrophysiological methods to examine the relationship
      between thalamocortical patches and auditory cortical maps. Biotinylated dextran
      amine was deposited into physiologically characterized sites in the ventral
      division of the medial geniculate body of New Zealand white rabbits.
      Approximately 7 d later, the animal was again anesthetized and the ipsilateral
      auditory cortex was mapped with tungsten microelectrodes. Multi-unit
      physiological data were obtained for the following characteristics: best
      frequency (BF), binaurality, response type, latency, sharpness of tuning, and
      threshold. Immunocytochemical methods were used to reveal the injection site in
      the ventral division of the medial geniculate body as well as the anterogradely
      labeled thalamocortical afferents in the auditory cortex. In 86% of the cases (12
      of 14), entry into a thalamocortical patch was associated with a marked change in
      physiological responses. A consistent BF and binaural class were usually observed
      within a patch. The patches appear to innervate distinct functional regions
      coding frequency and binaurality. A model is presented showing how patchy
      thalamocortical projections participate in the formation of tonotopic and
      binaural maps in primary auditory cortex.

PMID- 12514230
TI  - Olfactory signal transduction in the mouse septal organ.
AB  - The septal organ, a distinct chemosensory organ observed in the mammalian nose,
      is essentially a small island of olfactory neuroepithelium located bilaterally at
      the ventral base of the nasal septum. Virtually nothing is known about its
      physiological properties and function. To understand the nature of the sensory
      neurons in this area, we studied the mechanisms underlying olfactory signal
      transduction in these neurons. The majority of the sensory neurons in the septal
      organ express olfactory-specific G-protein and adenylyl cyclase type III,
      suggesting that the cAMP signaling pathway plays a critical role in the septal
      organ as in the main olfactory epithelium (MOE). This is further supported by
      patch-clamp recordings from individual dendritic knobs of the sensory neurons in
      the septal organ. Odorant responses can be mimicked by an adenylyl cyclase
      activator and a phosphodiesterase inhibitor, and these responses can be blocked
      by an adenylyl cyclase inhibitor. There is a small subset of cells in the septal
      organ expressing a cGMP-stimulated phosphodiesterase (phosphodiesterase 2), a
      marker for the guanylyl cyclase-D subtype sensory neurons identified in the MOE.
      The results indicate that the septal organ resembles the MOE in major olfactory
      signal transduction pathways, odorant response properties, and projection to the
      main olfactory bulb. Molecular and functional analysis of the septal organ, which
      constitutes approximately 1% of the olfactory epithelium, will provide new
      insights into the organization of the mammalian olfactory system and the unique
      function this enigmatic organ may serve.

PMID- 12514231
TI  - Activation of a subset of lumbar spinothalamic neurons after copulatory behavior
      in male but not female rats.
AB  - The precise pathways that convey copulation-related information to forebrain
      regions activated during male and female sexual behavior are poorly understood.
      Previous work from our laboratory and others has demonstrated the existence of a
      spinothalamic pathway that is a candidate to relay information to these areas.
      This pathway originates from a population of spinothalamic neurons in the lumbar
      spinal cord containing several neuropeptides including galanin, located in
      laminas 7 and 10 of the lumbar segments 3 and 4. To investigate the involvement
      of these lumbar spinothalamic neurons in conveying copulation-related
      information, we tested the hypothesis that these cells are activated after
      ejaculation in male rats and vaginocervical stimulation in female rats. This was
      assessed using galanin or cholecystokinin as a marker for this subset of
      spinothalamic neurons and Fos-immunoreactivity as a marker for neuronal
      activation. The results demonstrated that activation of these spinothalamic
      neurons is triggered by stimuli associated with ejaculation. Fos induction was
      specifically associated with ejaculation, because mounts or intromissions did not
      trigger expression. Moreover, these spinothalamic neurons were not activated by
      vaginocervical stimulation in female rats. Spinothalamic neurons have generally
      been associated with signaling pain and temperature information. The present
      findings demonstrate that a specific subpopulation of spinothalamic neurons
      signals information associated with ejaculation.

PMID- 12514232
TI  - Modulatory effects of alpha1-,alpha2-, and beta -receptor agonists on feline
      spinal interneurons with monosynaptic input from group I muscle afferents.
AB  - Previous studies have shown that monoamines may modulate operation of spinal
      neuronal networks by depressing or facilitating responses of the involved
      neurons. Recently, activation of interneurons mediating reciprocal inhibition
      from muscle spindle (Ia) afferents and nonreciprocal inhibition from muscle
      spindle and tendon organ (Ia/Ib) afferents in the cat was found to be facilitated
      by noradrenaline (NA). However, which subclass membrane receptors are involved in
      mediating this facilitation was not established; the aim of the present
      experiments was to investigate this. Individual Ia- and Ia/Ib-inhibitory
      interneurons were identified in the cat lumbar spinal cord, and NA agonists were
      applied close to these neurons by ionophoresis. The agonists included the alpha1
      receptor agonist phenylephrine, the alpha2-receptor agonists clonidine and
      tizanidine, and the beta-receptor agonist isoproterenol. Effects were measured by
      comparing changes in the number of extracellularly recorded spike potentials
      evoked by electrical stimulation of muscle nerves and changes in the latency of
      these potentials before, during, and after application of the tested compounds.
      Results show that the facilitatory effect of phenylephrine is as strong as that
      of NA, whereas the facilitatory effect of isoproterenol is weaker. Clonidine
      depressed activity of both Ia- and Ia/Ib-inhibitory interneurons, whereas
      tizanidine had no effect. These findings lead to the conclusion that beneficial
      antispastic effects of clonidine and tizanidine in humans are unlikely to be
      associated with an enhancement of the actions of Ia- and Ia/Ib-inhibitory
      interneurons, and the findings also support previous proposals that these
      compounds exert their antispastic actions via effects on other neuronal
      populations.

PMID- 12514233
TI  - The receptive fields of inferior temporal cortex neurons in natural scenes.
AB  - Inferior temporal cortex neurons have generally been found to have large visual
      receptive fields that typically include the fovea and extend throughout much of
      the visual field. However, a problem of such a large receptive field is that it
      does not easily support object selection by subsequent processing areas, in that
      all objects within such a large receptive field might activate inferior temporal
      cortex cells. To clarify this, we recorded from inferior temporal cortex neurons
      while macaques searched for objects in complex natural scenes or in plain
      backgrounds, as normally used. Inferior temporal cortex neuron receptive fields
      were much smaller in natural scenes (mean radius, 11 degrees) than in plain
      backgrounds (39 degrees). With two objects in a scene, one of which was a target
      for action (a touch), the firing rates were equally high during foveation of the
      effective stimulus when it was the target and when it was the distractor in both
      the plain and the complex scenes. With a plain background and two objects
      present, the receptive fields were much larger (24 degrees ) for the stimulus
      when it was the target than when it was the distractor (9 degrees ). This effect
      of object-based attention was much less evident in the complex scene, when the
      receptive fields were small both when the stimulus was a distractor and when it
      was a target. The results show that the temporal visual cortex provides an
      unambiguous representation in natural scenes by responding to the object shown at
      or close to the fixation point.

PMID- 12514234
TI  - Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs
      and is required for antidepressant-induced behavioral effects.
AB  - Recent studies have indicated that exogenously administered neurotrophins produce
      antidepressant-like behavioral effects. We have here investigated the role of
      endogenous brain-derived neurotrophic factor (BDNF) and its receptor trkB in the
      mechanism of action of antidepressant drugs. We found that trkB.T1-overexpressing
      transgenic mice, which show reduced trkB activation in brain, as well as
      heterozygous BDNF null (BDNF(+/)-) mice, were resistant to the effects of
      antidepressants in the forced swim test, indicating that normal trkB signaling is
      required for the behavioral effects typically produced by antidepressants. In
      contrast, neurotrophin-3(+/)- mice showed a normal behavioral response to
      antidepressants. Furthermore, acute as well as chronic antidepressant treatment
      induced autophosphorylation and activation of trkB in cerebral cortex,
      particularly in the prefrontal and anterior cingulate cortex and hippocampus.
      Tyrosines in the trkB autophosphorylation site were phosphorylated in response to
      antidepressants, but phosphorylation of the shc binding site was not observed.
      Nevertheless, phosphorylation of cAMP response element-binding protein was
      increased by antidepressants in the prefrontal cortex concomitantly with trkB
      phosphorylation and this response was reduced in trkB.T1-overexpressing mice. Our
      data suggest that antidepressants acutely increase trkB signaling in a BDNF
      dependent manner in cerebral cortex and that this signaling is required for the
      behavioral effects typical of antidepressant drugs. Neurotrophin signaling
      increased by antidepressants may induce formation and stabilization of synaptic
      connectivity, which gradually leads to the clinical antidepressive effects and
      mood recovery.

PMID- 12514235
TI  - Experience-dependent plasticity is impaired in adult rat barrel cortex after
      whiskers are unused in early postnatal life.
AB  - The capacity of adult barrel cortex to show experience-dependent plasticity after
      early restricted neonatal sensory deprivation was analyzed in barrel field cortex
      neurons. Selective sensory deprivation was induced by trimming two whiskers from
      postnatal day 0 (P0) to P21, namely, the principal D2 whisker plus one adjacent
      surround whisker (D3). At maturity (P90), responses of supragranular (layer
      II/III) and barrel (layer IV) neurons, all located in the D2 barrel column, were
      analyzed for modified responses to the deprived principal whisker (D2) and the
      nondeprived (D1) and deprived (D3) adjacent surround whiskers. For supragranular
      neurons, the responses to both principal and surround whiskers were reduced at
      maturity, whereas the barrel neurons showed mildly elevated responses to the
      principal whisker but a reduced response to the deprived surround whisker. In
      normal adult rats, trimming all but the principal D2 whisker and an adjacent D3
      whisker for 3 d (whisker pairing) produced the expected bias: elevated responses
      from the intact D3 compared with the cut D1 whisker in both barrel and
      supragranular neurons. When the neonatally deprived D2 and D3 whiskers were
      paired at maturity, a similar D3/D1 bias was generated in barrel neurons, but no
      bias occurred in supragranular neuron responses. Pairing the maintained D1 and
      deprived D2 whiskers produced a much greater bias toward D1 compared with the
      deprived D3 whisker in barrel neurons than in supragranular neurons. There were
      minimal effects on response latencies in layer IV under any of the experimental
      conditions. These findings indicate that a restricted period of sensory
      deprivation in early postnatal life (1) impairs intracortical relay of deprived
      inputs from layer IV to layer II/III in barrel cortex at maturity and (2)
      degrades receptive field plasticity of the supragranular layer cells but not the
      thalamic-recipient barrel neurons.

PMID- 12514236
TI  - New directions to post-genomic cell wall research.

PMID- 12514237
TI  - Towards understanding the role of membrane-bound endo-beta-1,4-glucanases in
      cellulose biosynthesis.
AB  - Recent studies have highlighted the involvement of membrane-anchored endo-beta
      1,4-glucanases in cellulose biosynthesis in plants, suggesting that there are
      parallels with Agrobacterium tumefaciens and other bacteria which also require
      endo-beta-1,4-glucanases for cellulose synthesis. This review summarises recent
      literature on endo-beta-1,4-glucanases and their role in plant development and
      addresses the possible functions of membrane-anchored isoforms in the synthesis
      of cellulose.

PMID- 12514238
TI  - Cellulose biosynthesis in plants: from genes to rosettes.
AB  - Modern techniques of gene cloning have identified the CesA genes as encoding the
      probable catalytic subunits of the plant CelS, the cellulose synthase enzyme
      complex visualized in the plasma membrane as rosettes. At least 10 CesA isoforms
      exist in Arabidopsis and have been shown by mutant analyses to play distinct
      role/s in the cellulose synthesis process. Functional specialization within this
      family includes differences in gene expression, regulation and, possibly,
      catalytic function. Current data points towards some CesA isoforms potentially
      being responsible for initiation or elongation of the recently identified sterol
      beta-glucoside primer within different cell types, e.g. those undergoing either
      primary or secondary wall cellulose synthesis. Different CesA isoforms may also
      play distinct roles within the rosette, and there is some circumstantial evidence
      that CesA genes may encode the catalytic subunit of the mixed linkage glucan
      synthase or callose synthase. Various other proteins such as the Korrigan
      endocellulase, sucrose synthase, cytoskeletal components, Rac13, redox proteins
      and a lipid transfer protein have been implicated to be involved in synthesizing
      cellulose but, apart from CesAs, only Korrigan has been definitively linked with
      cellulose synthesis. These proteins should prove valuable in identifying
      additional CelS components.

PMID- 12514239
TI  - The XTH family of enzymes involved in xyloglucan endotransglucosylation and
      endohydrolysis: current perspectives and a new unifying nomenclature.
AB  - The polysaccharide xyloglucan is thought to play an important structural role in
      the primary cell wall of dicotyledons. Accordingly, there is considerable
      interest in understanding the biochemical basis and regulation of xyloglucan
      metabolism, and research over the last 16 years has identified a large family of
      cell wall proteins that specifically catalyze xyloglucan endohydrolysis and/or
      endotransglucosylation. However, a confusing and contradictory series of
      nomenclatures has emerged in the literature, of which xyloglucan
      endotransglycosylases (XETs) and endoxyloglucan transferases (EXGTs) are just two
      examples, to describe members of essentially the same class of genes/proteins.
      The completion of the first plant genome sequencing projects has revealed the
      full extent of this gene family and so this is an opportune time to resolve the
      many discrepancies in the database that include different names being assigned to
      the same gene. Following consultation with members of the scientific community
      involved in plant cell wall research, we propose a new unifying nomenclature that
      conveys an accurate description of the spectrum of biochemical activities that
      cumulative research has shown are catalyzed by these enzymes. Thus, a member of
      this class of genes/proteins will be referred to as a xyloglucan
      endotransglucosylase/hydrolase (XTH). The two known activities of XTH proteins
      are referred to enzymologically as xyloglucan endotransglucosylase (XET, which is
      hereby re-defined) activity and xyloglucan endohydrolase (XEH) activity. This
      review provides a summary of the biochemical and functional diversity of XTHs,
      including an overview of the structure and organization of the Arabidopsis XTH
      gene family, and highlights the potentially important roles that XTHs appear to
      play in numerous examples of plant growth and development.

PMID- 12514240
TI  - The growing world of expansins.
AB  - Expansins are cell wall proteins that induce pH-dependent wall extension and
      stress relaxation in a characteristic and unique manner. Two families of
      expansins are known, named alpha- and beta-expansins, and they comprise large
      multigene families whose members show diverse organ-, tissue- and cell-specific
      expression patterns. Other genes that bear distant sequence similarity to
      expansins are also represented in the sequence databases, but their biological
      and biochemical functions have not yet been uncovered. Expansin appears to weaken
      glucan-glucan binding, but its detailed mechanism of action is not well
      established. The biological roles of expansins are diverse, but can be related to
      the action of expansins to loosen cell walls, for example during cell
      enlargement, fruit softening, pollen tube and root hair growth, and abscission.
      Expansin-like proteins have also been identified in bacteria and fungi, where
      they may aid microbial invasion of the plant body.

PMID- 12514241
TI  - The NADPH:quinone oxidoreductase P1-zeta-crystallin in Arabidopsis catalyzes the
      alpha,beta-hydrogenation of 2-alkenals: detoxication of the lipid peroxide
      derived reactive aldehydes.
AB  - P1-zeta-crystallin (P1-ZCr) is an oxidative stress-induced NADPH:quinone
      oxidoreductase in Arabidopsis thaliana, but its physiological electron acceptors
      have not been identified. We found that recombinant P1-ZCr catalyzed the
      reduction of 2-alkenals of carbon chain C(3)-C(9) with NADPH. Among these 2
      alkenals, the highest specificity was observed for 4-hydroxy-(2E)-nonenal (HNE),
      one of the major toxic products generated from lipid peroxides. (3Z)-Hexenal and
      aldehydes without alpha,beta-unsaturated bonds did not serve as electron
      acceptors. In the 2-alkenal molecules, P1-ZCr catalyzed the hydrogenation of
      alpha,beta-unsaturated bonds, but not the reduction of the aldehyde moiety, to
      produce saturated aldehydes, as determined by gas chromatography/mass
      spectrometry. We propose the enzyme name NADPH:2-alkenal alpha,beta-hydrogenase
      (ALH). A major portion of the NADPH-dependent HNE-reducing activity in A.
      thaliana leaves was inhibited by the specific antiserum against P1-ZCr,
      indicating that the endogenous P1-ZCr protein has ALH activity. Because
      expression of the P1-ZCr gene in A. thaliana is induced by oxidative stress
      treatments, we conclude that P1-ZCr functions as a defense against oxidative
      stress by scavenging the highly toxic, lipid peroxide-derived alpha,beta
      unsaturated aldehydes.

PMID- 12514242
TI  - Phosphatidylglycerol is essential for the development of thylakoid membranes in
      Arabidopsis thaliana.
AB  - Phosphatidylglycerol is a ubiquitous phospholipid in the biological membranes of
      many organisms. In plants, phosphatidylglycerol is mainly present in thylakoid
      membranes and has been suggested to play specific roles in photosynthesis. Here,
      we have isolated two T-DNA tagged lines of Arabidopsis thaliana that have a T-DNA
      insertion in the PGP1 gene encoding a phosphatidylglycerolphosphate synthase
      involved in the biosynthesis of phosphatidylglycerol. In homozygous plants of the
      T-DNA tagged lines, the PGP1 gene was completely disrupted. The growth of these
      knockout mutants was dependent on the presence of sucrose in the growth medium,
      and these plants had pale yellow-green leaves. The leaves of the mutants had
      remarkably large intercellular spaces due to the reduction in the number of
      mesophyll cells. The development of chloroplasts in the leaf cells was severely
      arrested in the mutants. Mesophyll cells with chloroplast particles are only
      found around vascular structures, whereas epidermal cells are enlarged but
      largely conserved. The content of phosphatidylglycerol in the mutants was reduced
      to 12% of that of the wild type. These results demonstrate that PGP1 plays a
      major role in the biosynthesis of phosphatidylglycerol in chloroplasts, and that
      phosphatidylglycerol is essential for the development of thylakoid membranes in
      A. thaliana.

PMID- 12514243
TI  - Regulation of gene expression in Arabidopsis thaliana by artificial zinc finger
      chimeras.
AB  - The artificial regulation of endogenous gene expression in plants is limited to
      only a few approaches. Here, we describe the use of artificial zinc finger
      chimeras to regulate the expression of a known reporter construct. The artificial
      zinc finger chimera TFIIIAZif is a fusion protein consisting of the four zinc
      fingers of TFIIIA linked through a spacer region to the three zinc fingers of
      Zif268. This artificial zinc finger chimera is able to bind specifically to a
      target DNA sequence (ZBS, zinc finger binding site) of 27 base pairs (bp).
      TFIIIAZif was fused to a transactivation domain from the herpes simplex virus
      VP16 or its tetramer VP64 to give ZF-VP16 or ZF-VP64, respectively. In transient
      expression assays, these two transcription activators were able to activate a
      target reporter gene (luc and GFP) expressed from a minimal -46 35S promoter
      linked to four copies of ZBS. The activation was confirmed in transgenic plants
      using an inducible XVE system [Zuo et al. (2000) Plant J. 24: 265] to express ZF
      VP16 or ZF-VP64. Furthermore, to test the specificity of ZF-VP64 we have compared
      reporter gene expression from a wild type (1xZBS) and a mutant (1xZBSmu) binding
      site in transgenic plants. The 1xZBS was used to express green fluorescent
      protein (GFP) whereas the 1xZBSmu was used to express red fluorescent protein
      (RFP). Upon induction of ZF-VP64 we found a much higher expression of GFP (about
      33-fold) as compared to RFP expression. These results suggest that artificial
      zinc finger chimeras can be used to target specific DNA sequences and to regulate
      gene expression in plants.

PMID- 12514244
TI  - ABA-activated SnRK2 protein kinase is required for dehydration stress signaling
      in Arabidopsis.
AB  - Protein phosphorylation has pivotal roles in ABA and osmotic stress signaling in
      higher plants. Two protein phosphatase genes, ABI1 and ABI2, are known to
      regulate these signaling pathways in Arabidopsis: The identity of ABA-activated
      protein kinases required for the ABA signaling, however, remains to be
      elucidated. Here we demonstrate that two protein kinases, p44 and p42, were
      activated by ABA in Arabidopsis T87 cultured cells, and at least one protein
      kinase, p44, was activated not only by ABA but also by low humidity in
      Arabidopsis plants. Analysis of T-DNA knockout mutants and biochemical analysis
      using a specific antibody revealed that the p44 is encoded by a SnRK2-type
      protein kinase gene, SRK2E. The srk2e mutation resulted in a wilty phenotype
      mainly due to loss of stomatal closure in response to a rapid humidity decrease.
      ABA-inducible gene expression of rd22 and rd29B was suppressed in srk2e. These
      results show that SRK2E plays an important role in ABA signaling in response to
      water stress.

PMID- 12514245
TI  - Preferential and asymmetrical accumulation of a Rac small GTPase mRNA in
      differentiating xylem cells of Zinnia elegans.
AB  - Rac-type small GTPases are known to function in some cellular processes in
      plants. To further understand the involvement of Rac type GTPases in plant
      development, we isolated from cultured Zinnia cells a gene (ZeRAC2) encoding a
      new Rac-type small GTPase. ZeRAC2 mRNA accumulates preferentially in xylogenic
      culture and transiently at the time when visible tracheary elements appear.
      Experiments with ZeRAC2 recombinant proteins demonstrated that ZeRAC2 binds to
      and hydrolyzes GTP. A GFP-ZeRAC2 fusion protein was localized to the plasma
      membrane. Together with the fact that ZeRAC2 possesses a putative
      geranylgeranylation site at the C-terminus, this suggests that ZeRAC2 acts on the
      plasma membrane. In situ hybridization indicated that ZeRAC2 mRNA accumulates
      preferentially in xylem parenchyma and tracheary element precursor cells, and
      surprisingly the accumulation is restricted to the site facing developing
      tracheary elements.

PMID- 12514246
TI  - Regulation of sulfur-responsive gene expression by exogenously applied cytokinins
      in Arabidopsis thaliana.
AB  - Effects of plant hormones on a sulfur-deficiency responsive element (betaSR) from
      the promoter region of the beta subunit gene of beta-conglycinin, a major seed
      storage protein of soybean, were investigated using transgenic Arabidopsis
      thaliana. Among the hormones tested, the cytokinins, trans-zeatin (Z) and trans
      zeatin riboside, upregulated gene expression directed by the betaSR element both
      in the presence and in the absence of sulfate in the medium. Z also increased
      transcript accumulation of two endogenous sulfur-responsive genes, the adenosine
      5'-phosphosulfate reductase (APR1) and the Sultr2;2, a sulfate transporter.
      Concentrations of cytokinins were unaltered during early stages of sulfur
      starvation when expression of these genes was upregulated. Z did not alter
      concentrations of O-acetyl-L-serine, a positive regulator of gene expression in
      sulfur starvation response. Concentrations of sucrose, which is known to
      upregulate expression of APR1, were increased in rosette leaves by Z. Sucrose
      application to the medium also increased expression directed by the betaSR
      element, although sucrose concentrations in tissues were not significantly
      altered by sulfur availability. These results suggest that exogenously applied
      cytokinins positively regulate expression of these sulfur responsive genes
      through a pathway independent of that from sulfur starvation, possibly through
      increasing sucrose concentrations in tissues.

PMID- 12514247
TI  - Biosynthesis of sterols and triterpenes in cell suspension cultures of Uncaria
      tomentosa.
AB  - Pectin administered to Uncaria tomentosa cell suspension cultures, was found to
      increase the production of triterpene acids (ursolic and oleanolic acid),
      however, neither growth nor sterol accumulation were affected. Cell cultures
      showed that pectin treatment caused a rapid threefold increase in the activities
      of enzymes involved in the biosynthesis of C(5) and C(30 )isoprenoid, such as
      isopentenyl diphosphate isomerase and squalene synthase. The activity of a
      farnesyl diphosphatase, which could divert the flux of farnesyl diphosphate to
      farnesol, was two times lower in elicited than in control cells. Elicited cells
      also transformed more rapidly a higher percentage of [5-(3)H]mevalonic acid into
      triterpene acids. Interestingly, addition of terbinafine, an inhibitor of
      squalene epoxidase, to elicited cell cultures inhibited sterol accumulation while
      triterpene production was not inhibited. These results suggest that in U.
      tomentosa cells, both the previously mentioned enzymes and those involved in
      squalene 2,3-oxide formation play an important regulatory role in the
      biosynthesis of sterols and triterpenes.

PMID- 12514248
TI  - Utilization and transport of glucose in Olea Europaea cell suspensions.
AB  - Cell suspensions of Olea europaea var. Galega Vulgar grown in batch culture with
      0.5% (w/v) glucose were able to transport D-[(14)C]glucose according to Michaelis
      Menten kinetics associated with a first-order kinetics. The monosaccharide
      carrier exhibited high affinity (K(m) approximately 50 micro M) and was able to
      transport D-glucose, D-fructose, D-galactose, D-xylose, 2-deoxy-D-glucose and 3-O
      methyl-D-glucose, but not D-arabinose, D-mannitol or L-glucose. D-[(14)C]glucose
      uptake was associated with proton uptake, which also followed Michaelis-Menten
      kinetics. The transport of 3-O-methyl-D-glucose was accumulative (40-fold, at pH
      5.0) and the protonophore carbonyl cyanide m-chlorophenylhydrazone strongly
      inhibited sugar accumulation. The results were consistent with the involvement of
      a monosaccharide: proton symporter with a stoichiometry of 1 : 1. When cells were
      grown with 3% (w/v) glucose, the uptake of D-[(14)C]glucose followed first-order
      kinetics and monosaccharide:proton symporter activity was not detected. The value
      obtained for the permeability coefficient of hexoses in O. europaea cells
      supported the hypothesis that the first-order kinetics observed in 0.5% and 3%
      sugar-grown cells was produced exclusively by passive diffusion of the sugar. The
      results indicate that in O. europaea cells sugar levels have a regulatory effect
      on sugar transport, because the activity for monosaccharide transport was
      repressed by high sugar concentrations.

PMID- 12514249
TI  - Chloroplast transformation with modified accD operon increases acetyl-CoA
      carboxylase and causes extension of leaf longevity and increase in seed yield in
      tobacco.
AB  - Acetyl-CoA carboxylase (ACCase) in plastids is a key enzyme regulating the rate
      of de novo fatty acid biosynthesis in plants. Plastidic ACCase is composed of
      three nuclear-encoded subunits and one plastid-encoded accD subunit. To boost
      ACCase levels, we examined whether overexpression of accD elevates ACCase
      production. Using homologous recombination, we replaced the promoter of the accD
      operon in the tobacco plastid genome with a plastid rRNA-operon (rrn) promoter
      that directs enhanced expression in photosynthetic and non-photosynthetic organs,
      and successfully raised the total ACCase levels in plastids. This result suggests
      that the level of the accD subunit is a determinant of ACCase levels, and that
      enzyme levels are in part controlled post-transcriptionally at the level of
      subunit assembly. The resultant transformants grew normally and the fatty acid
      content was significantly increased in leaves, but not significantly in seeds.
      However, the transformants displayed extended leaf longevity and a twofold
      increase of seed yield over the control value, which eventually almost doubled
      the fatty acid production per plant of the transformants relative to control and
      wild-type plants. These findings offer a potential method for raising plant
      productivity and oil production.

PMID- 12514250
TI  - QTL analysis of Al tolerance in recombinant inbred lines of Arabidopsis thaliana.
AB  - Quantitative trait loci (QTLs) and epistasis for Arabidopsis thaliana aluminum
      (Al) tolerance were analyzed using a recombinant inbred (RI) population of 100
      lines derived from a cross between Landsberg erecta and Columbia (Col). Root
      growth of the RI population was determined in hydroponics using solutions
      containing 0 or 4 micro M of AlCl(3 )and a series of nutrients, except P(i), at
      pH 5.0. Al tolerance was defined as relative root length [RRL: plus Al/minus Al
      (%)], and the RI lines ranged from 22.6 to 97.4% with a broad sense heritability
      of 0.99. Using the composite interval mapping method, two significant single
      factor QTLs (P<0.05) were detected by RRL on chromosomes 1 and 4, where the Col
      allele showed positive and negative effects on the Al tolerance. These QTLs could
      explain about 43% of the total variation of Al tolerance among the RI population.
      On the other hand, five epistatic loci pairs were identified by the complete pair
      wise search method (P<0.0005). No single factor QTL and epistatic loci pairs were
      shared by the root length in the control and the RRL, suggesting that the loci
      identified by the RRL would be specific for Al treatment and controlling Al
      tolerance among the RI population.

PMID- 12514251
TI  - Amyloplast formation in cultured tobacco BY-2 cells requires a high cytokinin
      content.
AB  - When cytokinin-autonomous tobacco BY-2 cell cultures are transferred into 2,4
      dichlorophenoxyacetic acid (2,4-D)-deprived medium, amyloplast development is
      initiated. Using this in vitro amyloplast-inducing system, the role of cytokinins
      in amyloplast formation was investigated. We show that addition of lovastatin, an
      inhibitor of mevalonate synthesis, to amyloplast-inducing medium reduced starch
      accumulation. Microscopic observation also revealed that lovastatin treatment
      decreased starch deposition; however, the overall morphologies of cells and
      plastids were less affected than control cell cultures. In addition, lovastatin
      lowered the transcription level of the ADP-glucose pyrophosphorylase small
      subunit (AgpS) gene. Application of mevalonate or zeatin dramatically restored
      the decrease in starch deposition, and restored AgpS mRNA accumulation. Moreover,
      addition of other molecules with cytokinin activity, such as adenine- and
      phenylurea-type compounds, restored starch accumulation and AgpS transcript
      levels, whereas other isopentenyl pyrophosphate-derived phytohormones did not.
      Liquid chromatography-mass spectrometry/mass spectrometry quantification of
      endogenous cytokinins revealed that endogenous cytokinins increased when BY-2
      cells were transferred into 2,4-D-deprived medium from conventional medium
      containing 2,4-D. In addition, lovastatin treatment decreased endogenous
      cytokinins to some extent when cultured under 2,4-D-deprived conditions. Our
      results suggest that both 2,4-D deprivation and an increase in endogenous
      cytokinins have important roles in accelerating the changes in plastid
      morphology, starch accumulation, and AgpS gene expression.

PMID- 12514252
TI  - Ordered cosmid library of the Mesorhizobium loti MAFF303099 genome for systematic
      gene disruption and complementation analysis.
AB  - For effective exploitation of the genome sequence information of Lotus
      microsymbiont, Mesorhizobium loti MAFF303099, to discover gene functions, we have
      constructed an ordered and mutually overlapping cosmid library using an IncP
      broad host-range vector. The library consisted of 480 clones to cover
      approximately 99.6% of the genome with average insert size and overlap of 26.9
      and 11.1 kbp, respectively. The genome of M. loti consists of a single chromosome
      and two plasmids. The chromosome (7,036,071 bp) was covered 99.68% by 445 clones
      with four gaps, although two clones were unstable in E. coli. The larger plasmid
      pMLa (351,911 bp) was completely covered by 23 clones, while the smaller pMLb
      (208,315 bp) was covered 98.85% by 12 clones with two gaps. We have also made
      ancillary plasmids to facilitate the construction of deletion mutants using
      derivatives of the library clones. As a pilot experiment to uncover regions which
      contain novel symbiotic genes, 13 deletion mutants were constructed to lack in
      total 180.5 kbp of the genome. All the mutants formed apparently normal nodules
      and supported symbiotic nitrogen fixation, however, one mutant that lacked a 5.3
      kbp chromosomal region, 4,551,930-4,557,222, did not produce normal
      exopolysaccharides as judged by fluorescence on medium containing Calcofluor. The
      results supported the effectiveness of the approach to detect gene functions.

PMID- 12514253
TI  - Molecular properties of a matrix attachment region-binding protein located in the
      nucleoli of tobacco cells.
AB  - We cloned a cDNA for matrix-attachment region (MAR)-binding protein from
      Nicotiana tabacum cells to elucidate the structure and function of the nuclear
      matrix. The cDNA encodes a protein of 555 amino acids (61,050 Da) with an
      isoelectric point of 9.4. We named the protein NtMARBP61. The sequence is 45%
      identical to yeast Nop58p, which is involved in rRNA processing. The C-terminal
      part is unique and rich in lysine residues. The recombinant C-terminal part had
      the ability to bind double-stranded DNAs of 12 tobacco MARs. The intracellular
      localization was determined to be in the nucleolus by fluorescent microscopy
      using the antibody to the recombinant NtMARBP61. The mRNA level was high in the
      lag and early-log phases of cultured cells but low in the stationary phase. The
      protein was accumulated only in the middle- and late-log phases, suggesting that
      NtMARBP61 is essential for growing cells. The results suggest at least the
      structural and regulatory function of NtMARBP61 in the nucleolus as a MAR-binding
      protein in a growth-stage specific manner.

PMID- 12514254
TI  - Salt stress-induced dissociation from cells of a germin-like protein with Mn-SOD
      activity and an increase in its mRNA in a moss, Barbula unguiculata.
AB  - To estimate the physiological roles of a germin-like protein (BuGLP) with Mn-SOD
      activity isolated newly from a moss, Barbula unguiculata, BuGLP mRNA levels
      during cell growth and the effects of methyl viologen and salt stress were
      studied. BuGLP mRNA levels were at their peak during the exponential phase of
      growth and decreased thereafter, but SOD activity was held at the same level as
      that during the exponential phase. When methyl viologen was present as a
      generator of superoxide the amount of BuGLP transcripts decreased, but that of
      SOD activity of BuGLP bound to the cell wall was not affected. The addition of
      NaCl to the cells during the logarithmic phase increased both the BuGLP mRNA
      levels and total SOD activity of BuGLP, but decreased the SOD activity bound to
      the cell wall due to release of most of the SOD activity into the medium. On the
      other hand, the addition of NaCl to the cells during the stationary phase hardly
      affected BuGLP mRNA levels or SOD activity levels bound to the cell wall. These
      results suggest that the induction of BuGLP gene by salt stress is caused by
      dissociation of BuGLP protein from the cell wall into the medium in the cells
      during the logarithmic phase.

PMID- 12514255
TI  - Electrical perception of "death message" in chara: analysis of rapid component
      and ionic process.
AB  - Electrical response upon wounding was analyzed in Chara corallina. A specimen
      comprising two adjoining internodal cells was prepared. One cell (victim cell)
      was killed by cutting and any changes in the membrane potential of the
      neighboring cell (the receptor cell) were measured. Upon cutting the victim cell,
      the receptor cell generated four kinds of depolarizations: (1) rapid component,
      (2) slow and long-lasting component, (3) action potential and (4) small spike.
      Rapid and slow components were observed in most cells. On the other hand, the
      action potential and small spike were not always ubiquitous among specimens. When
      an action potential was generated just after cutting the victim cell, the rapid
      component could not be observed due to masking by the action potential. It was
      suggested that both rapid and slow components were generated at the nodal end. On
      the other hand, action potentials were thought to be generated at the flank of
      the receptor cell. High turgor pressure of the cell was necessary for generating
      both rapid and slow components. Experiments under K(+)-induced depolarization
      unequivocally showed that the Cl(-) channel at the nodal end of the receptor cell
      was activated upon cutting the victim cell.

PMID- 12514256
TI  - Bipolar localization of putative photoreceptor protein for phototaxis in
      thermophilic cyanobacterium Synechococcus elongatus.
AB  - We identified an open reading frame from a database of the entire genome of
      Synechococcus elongatus, the product of which was very similar to pixJ1, which
      was proposed as photoreceptor gene for phototaxis in Synechocystis sp. PCC6803
      [Yoshihara et al. (2000) Plant Cell Physiol. 41: 1299]. The mRNA of S. elongatus
      pixJ (SepixJ) was expressed in vivo as a part of the product of an operon. SePixJ
      was detected exclusively in the membrane fraction after cell fractionation.
      Immunogold labeling of SePixJ in ultra-thin sections indicated that it existed
      only in both ends of the rod-shaped cell; probably bound with the cytoplasmic
      membrane.

PMID- 12514257
TI  - Effects of dietary fibers on magnesium absorption in animals and humans.
AB  - There is overwhelming evidence that dietary fibers are an important component of
      human and animal diets and play an important role in human health. Because
      dietary fibers and some associated substances, such as phytate, have in vitro
      mineral-binding capacities, they have been thought to impair absorption of
      minerals such as calcium, iron and zinc, although magnesium absorption seems to
      be less affected. Indeed, the effect of dietary fibers depends largely on their
      own nature and characteristics, and also on mineral homeostasis. In 1977 it was
      observed that resistant starch, a fermentable dietary fiber, could improve Mg
      absorption in rats. More recently, attention has been focused on other
      fermentable substrates such as inulin and oligo- or polysaccharides, for their
      potential prebiotic and health effects. Studies conducted on different types of
      fermentable carbohydrates have confirmed their beneficial effect on Mg absorption
      in different animal species. The majority of these studies have also sought to
      determine the effects of fibers on other minerals such as calcium, iron and zinc.
      In contrast to the studies with Mg, these studies did not show a consistent
      effect on the absorption of these minerals. This is due to the particularities of
      sites and mechanism of Mg absorption. To date, four human studies have been
      carried out that generally confirmed the enhancing effect of fermentable oligo-
      or polysaccharides on Mg absorption.

PMID- 12514258
TI  - Peter J. Reeds (February 22, 1945-August 13, 2002).

PMID- 12514259
TI  - A proteomic investigation of isolated soy proteins with variable effects in
      experimental and clinical studies.
AB  - Dietary preparations of soy proteins used for clinical studies, particularly of
      hypercholesterolemia, in Europe and the United States were the subject of a
      proteomic comparison because differences in their composition may explain
      variability in experimental and clinical results. After two-dimensional
      electrophoresis, identities of the protein components (globulin subunits and
      their breakdown products) were established by matrix-assisted laser
      desorption/ionization mass spectrometry. The soy concentrates (Cholsoy/Croksoy),
      which were used in most of the Italian and Swiss studies in which reductions in
      cholesterolemia occurred, exhibited a predominance of breakdown products of the
      7S globulin and mainly intact 11S globulin subunits. Soy isolates used in the
      United States (SUPRO) showed none of the major components corresponding to 7S
      globulin subunits; only some of the light chains of 11S were intact, and heavy
      chains of 11S also were fragmented. Ethanol- and nonethanol-treated SUPRO
      products showed considerable variability in their isoflavone concentrations and
      there seemed to be differential protein recoveries due to ethanol processing.
      These findings indicate differences in the protein composition of soy products
      used in clinical studies. We suggest that standardization should be improved
      before products are assessed for clinical outcome studies.

PMID- 12514260
TI  - Iron overload in hypercholesterolemic rats affects iron homeostasis and serum
      lipids but not blood pressure.
AB  - Epidemiologic and experimental data suggest that excess iron may contribute to
      the development of cardiovascular diseases (CVD). Because increased LDL
      cholesterol, decreased HDL cholesterol and alteration of systolic blood pressure
      (SBP) have all been implicated as risk factors for atherosclerosis and related
      CVD, the present study was designed to determine whether excess iron alters serum
      lipids and SBP in control and hypercholesterolemic rats. Female Fischer rats were
      divided into four groups. The control group (C) was fed the control diet, the CI
      group was fed the control diet and given iron dextran injections, the
      hypercholesterolemic group (H) was fed a 1 g/100 g cholesterol diet, and the HI
      group was fed the cholesterol diet and given iron dextran injections. The rats
      were fed the diets for 8 wk and iron dextran injections were given during wk 6 at
      doses of 10 mg/d for 5 d. Excess iron reduced (P < 0.01) plasma total cholesterol
      in rats fed the cholesterol diet (5.31 +/- 0.83 and 3.17 +/- 0.31 mmol/L for H
      and HI, respectively). Excess iron also resulted in a redistribution of
      cholesterol among the various lipoprotein fractions, with an increase (P < 0.01)
      in HDL cholesterol (0.56 +/- 0.12 and 0.85 +/- 0.16 mmol/L for H and HI,
      respectively) and a decrease (P < 0.01) in LDL cholesterol (4.49 +/- 0.77 and
      2.09 +/- 0.26 mmol/L for H and HI, respectively). This redistribution also
      occurred in the rats fed the control diet. The treatments did not affect SBP or
      heart rate. The high cholesterol diet affected iron homeostasis; group H had
      lower transferrin saturation than group C (P < 0.01); group HI had a lower serum
      iron concentration than group CI but did not differ from group H (P < 0.05).
      Therefore, we conclude that if iron has any effect on CVD, it is not through its
      influence on serum lipids and blood pressure.

PMID- 12514261
TI  - The prebiotic characteristics of fructooligosaccharides are necessary for
      reduction of TNBS-induced colitis in rats.
AB  - Fructooligosaccharides (FOS) increase the growth of lactic acid bacteria (LAB)
      and promote butyrate and lactate production. Because of these properties, FOS may
      benefit intestinal inflammation. The purpose of this study was to investigate the
      effect of FOS on colitis in rats and determine which factors are involved. Groups
      of rats with intracolonic trinitrobenzene sulfonic acid (TNBS)-induced colitis
      received intragastric infusions of 9 g/L NaCl, 1 g/d FOS or 10(11) colony-forming
      units (cfu)/d LAB (Experiment 1), or intracolonic infusions of 9 g/L NaCl,
      butyrate, lactate or butyrate + lactate with or without 10(9.5) cfu/d LAB
      (Experiment 2). Each infusion was administered twice daily for 14 d. Intragastric
      FOS reduced the gross score for inflammation (P < 0.001), myeloperoxidase (MPO)
      activity (P < 0.001) and pH (P < 0.001), and increased lactate (P = 0.02) and
      butyrate concentrations (P < 0.001) as well as LAB counts in the cecum (P <
      0.01). Intragastric LAB (10(11) cfu/d) had the same beneficial effects as FOS and
      modified the cecal composition similarly. High doses of intracolonic butyrate and
      lactate reduced the indices of inflammation (P < 0.001), whereas administration
      of the lower concentrations found in the colon tended to decrease (P < 0.1) the
      gross score for inflammation and MPO activity. Addition of LAB (10(9.5) cfu/d) to
      the organic acids was necessary to reproduce the significant FOS-induced effects
      on these variables. Thus, under the experimental conditions used, FOS reduced
      intestinal inflammatory activity mainly by increasing LAB counts in the
      intestine.

PMID- 12514262
TI  - Copper deficiency induces the upregulation of the copper chaperone for Cu/Zn
      superoxide dismutase in weanling male rats.
AB  - The most commonly used indices for determining copper deficiency in humans are
      reduced serum/plasma copper concentration and decreased activity of ceruloplasmin
      and Cu/Zn superoxide dismutase (SOD1). However, these indicators are influenced
      by many factors unrelated to copper status and lack the sensitivity required to
      detect marginal deficiency, limiting their usefulness in many situations. In
      vivo, the insertion of copper into SOD1 is dependent on the copper chaperone for
      SOD1 (CCS). In this study, we explored the possibility that the expression level
      of CCS may reflect copper status and thus serve as a useful marker of copper
      nutriture. Weanling male Wistar rats were fed either a normal (5.3 mg Cu/kg
      diet), moderately deficient (0.84 mg Cu/kg diet) or deficient (0.34 mg Cu/kg
      diet) copper diet for 6 wk. Rats fed moderate and deficient diets showed
      differences (P < 0.05) in several hematological measurements, indicating varying
      degrees of copper deficiency in these groups. Copper-deficient rats had reduced
      (P < 0.05) liver and erythrocyte SOD1 activity and body weight. Western blot
      analysis revealed a dose-dependent increase (P < 0.05) in CCS expression in liver
      and erythrocytes of copper-deficient rats. We report CCS protein level as a novel
      marker for assessing copper status.

PMID- 12514263
TI  - Glucose-6-phosphatase activity is not suppressed but the mRNA level is increased
      by a sucrose-enriched meal in rats.
AB  - The expression of glucose-6-phosphatase (G6Pase) mRNA is repressed by insulin and
      stimulated by cAMP and dexamethasone, with the insulin effect dominant. Both
      lipids and glucose increase the expression of G6Pase mRNA under conditions in
      which insulin is either absent or at basal levels. The aim of the present study
      was to investigate dietary nutrient regulation of G6Pase mRNA and protein under
      postprandial conditions. Male rats (n = 6-8/group) were deprived of food for 48 h
      and then either remained food deprived (FD) or were refed diets containing 68%
      cornstarch and 12% corn oil (ST; % energy), 68% sucrose and 12% corn oil (SU) or
      35% cornstarch and 45% corn oil (HF) for 3 h. Rats were anesthetized, blood was
      drawn from the portal vein, and the liver was removed and immediately processed
      for subsequent analyses. Energy intake over the 3-h refeeding period did not
      differ among groups (209 +/- 25 kJ). Portal vein glucose and insulin were 5.0 +/-
      0.2 mmol/L and 90 +/- 18 pmol/L, respectively, in FD rats and were not
      significantly different among the refed groups (14.5 +/- 1.2 mmol/L and 1302 +/-
      154 pmol/L, respectively). Compared with the FD rats, G6Pase mRNA was
      approximately 50% lower in ST and HF groups, whereas it was approximately 1.6
      fold higher in SU-refed rats (P < 0.05). G6Pase activity in whole liver
      homogenates was lower in ST and HF rats than in FD and SU rats. Insulin receptor
      substrate (IRS) phosphorylation, IRS-association with phosphatidylinositol 3
      (PI3)-kinase and activation of protein kinase B (PKB) were not significantly
      different among the refed groups. However, glycogen synthase kinase-3alpha
      phosphorylation was lower and cAMP response element binding protein (CREB)
      phosphorylation was higher in SU rats than in ST and HF refed groups. Thus, the
      postprandial environment after ingestion of sucrose appears to overcome the
      dominant effects of insulin on G6Pase mRNA, perhaps via cellular changes that
      reduce phosphorylation of, and therefore activate, glycogen synthase kinase
      3alpha.

PMID- 12514264
TI  - Plant-derived monoterpenes suppress hamster kidney cell 3-hydroxy-3
      methylglutaryl coenzyme a reductase synthesis at the post-transcriptional level.
AB  - The rate-limiting enzyme for mevalonate and cholesterol synthesis in mammalian
      cells is 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Control occurs
      through both transcriptional and post-transcriptional actions signaled by the end
      product, cholesterol, and by isoprenoid intermediates. End products of plant
      mevalonate metabolism, i.e., plant-derived isoprenoids, also suppress mammalian
      HMG-CoA reductase. Previous studies reported that isoprenoids suppress reductase
      synthesis at a post-transcriptional level. We tested the hypothesis that plant
      derived isoprenoids also regulate mammalian HMG-CoA reductase synthesis at a post
      transcriptional level by incubating lovastatin-treated C100 cells with mevalonate
      or a plant-derived isoprenoid (the monoterpenes, limonene, perillyl alcohol or
      geraniol) either alone or combined with the oxysterol, 25-hydroxycholesterol (25
      OH C). Mevalonate decreased HMG-CoA reductase synthesis and mRNA levels by 65 and
      66%, respectively (P < 0.05). The cyclic monoterpenes, limonene and perillyl
      alcohol, lowered HMG-CoA reductase synthesis by 70 and 89%, respectively (P <
      0.05); although neither reduced HMG-CoA reductase mRNA levels (P = 0.88).
      Geraniol, an acyclic monoterpene, suppressed HMG-CoA reductase synthesis by 98%
      and lowered mRNA levels by 66% (P < 0.05). A combination of 25-OH C and either
      mevalonate or any three monoterpenes reduced HMG-CoA reductase mRNA levels (P <
      0.05) compared with lovastatin-only treated cells. However, the dual combination
      of 25-OH C and either mevalonate or a monoterpene resulted in a greater decrease
      in HMG-CoA reductase synthesis than in mRNA levels. The difference between
      changes in HMG-CoA reductase synthesis and mRNA levels reflects a specific effect
      of isoprenoids on HMG-CoA reductase synthesis at the translational level.
      Mevalonate enhanced HMG-CoA reductase degradation, but no such effect was
      observed for the monoterpenes. These results indicate that the three plant
      derived isoprenoids primarily suppress HMG-CoA reductase synthesis at a post
      transcriptional level by attenuating HMG-CoA reductase mRNA translational
      efficiency.

PMID- 12514265
TI  - Pancreatic metallothionein-I may play a role in zinc homeostasis during maternal
      dietary zinc deficiency in mice.
AB  - Herein, the function of pancreatic metallothionein (MT)-I during zinc deficiency
      in pregnancy was examined using transgenic mice, which constitutively express the
      mouse MT-I gene driven by the rat elastase I promoter. Pancreatic MT protein
      levels and zinc levels were elevated significantly in the transgenic mice
      compared with those in control mice. Pregnant transgenic and control mice were
      fed zinc-deficient (1 micro g/g beginning at d 8) or zinc-adequate (50 micro g/g)
      diets during pregnancy, and the effects on the morphology of embryos were
      determined at d 14 of pregnancy (d 1 = vaginal plug). As other indicators of zinc
      deficiency, maternal pancreatic MT levels, as well as the expression of zinc
      regulated genes in the embryonic visceral yolk sac were examined. Under these
      experimental conditions of moderate dietary zinc deficiency, 21.3% of the embryos
      in control mice exhibited morphological defects, whereas only 5.8% of the embryos
      in the elastase-MT-I transgenic females had developed abnormally by d 14.
      Surprisingly, dietary zinc deficiency caused a >95% decrease in pancreatic MT
      protein concentration in these transgenic mice. This suggests the post
      transcriptional control of MT protein levels during zinc deficiency because the
      rat elastase I promoter is not metal-regulated. The decrease in pancreatic MT
      protein levels was paralleled by a dramatic decrease in the relative abundance of
      MT-I mRNA and a dramatic increase in the relative abundance of the zinc/iron
      regulated transporter-related zinc transporter-4 (ZIP4) mRNA in the embryonic
      visceral yolk sac. Thus, the constitutive overexpression of pancreatic MT-I in
      these mice attenuated, but did not prevent the effects of maternal or embryonic
      zinc deficiency under these conditions. Overall, these findings are consistent
      with the hypothesis that mouse pancreatic MT-I may participate in providing a
      labile pool of maternal zinc for the developing embryo during periods of zinc
      deficiency.

PMID- 12514266
TI  - The permissive effect of zinc deficiency on uroguanylin and inducible nitric
      oxide synthase gene upregulation in rat intestine induced by interleukin 1alpha
      is rapidly reversed by zinc repletion.
AB  - Deficient intake of zinc from the diet upregulates both uroguanylin (UG) and
      inducible nitric oxide synthase (iNOS) expression in rats. Because these changes
      influence intestinal fluid secretion and intestinal cell pathophysiology, they
      relate to the incidence of diarrheal disease and its reversal by zinc as well as
      intestinal inflammation in general. A model of moderate zinc deficiency in rats,
      which changes molecular indices of zinc deficiency, was used to further explore
      the effects of the proinflammatory cytokine interleukin (IL)-1alpha and zinc
      repletion on these changes. IL-1alpha has been shown to have a role in the
      intestinal inflammation that occurs with bacterial infection. Our results showed
      a permissive effect of zinc deficiency on both UG and iNOS expression.
      Specifically, UG expression was responsive to zinc deficiency and IL-1alpha
      challenge, which were additive when combined, whereas iNOS expression was
      upregulated by IL-1alpha only during the deficiency. Immunohistochemistry showed
      that the increase in UG was limited to enterocytes of the upper villus but, in
      contrast, the increase in iNOS was principally in cells of the lamina propria of
      IL-1alpha-treated rats. Cells exhibiting UG upregulation did not co-express
      serotonin. Repletion with zinc reversed upregulation of the iNOS gene within 1 d,
      whereas UG upregulation required 3-4 d to return to normal. This differential
      response to repletion suggests that mechanisms of UG and iNOS dysregulation are
      different. Dysregulation of both genes may contribute to the severity of zinc
      responsive diarrheal disease and intestinal inflammatory disease.

PMID- 12514267
TI  - Transcription profiling in rat liver in response to dietary docosahexaenoic acid
      implicates stearoyl-coenzyme a desaturase as a nutritional target for lipid
      lowering.
AB  - The gene expression profile in response to dietary docosahexaenoic acid rich oil
      for 6 wk was analyzed in the livers of male Sprague-Dawley rats to identify genes
      whose expression was regulated by dietary modification and correlated with serum
      lipid changes. Such genes may represent targets for intervention into
      cardiovascular health using nutraceuticals. High density glass microarrays
      containing approximately 7800 cloned expressed sequences from rat were used to
      identify those genes that responded to dietary long chain (n-3) fatty acids. In
      general, dietary long chain (n-3) fatty acids exhibited statistically significant
      lipid-lowering effects similar to a pharmaceutical alternative, fenofibrate, but
      showed narrower effects on the transcription of most of the genes assayed. The
      transcription patterns confirmed that the expression of several key genes
      involved in cholesterol metabolism, fatty acid beta-oxidation and lipogenesis was
      affected. These analyses indicated that stearoyl-coenzyme A (Delta9) desaturase,
      a key enzyme involved in the regulation of triglyceride biosynthesis and
      secretion, is a potential target for nutritional intervention for hyperlipidemia
      and cardiovascular health. In addition these results suggested that regulation of
      the farnesoid X receptor may be a key nutritionally regulated mediator of serum
      lipid changes. A nutritional product concept based on a convenient dietary aid
      demonstrated comparable efficacy with less spurious gene regulation than a
      pharmaceutical alternative.

PMID- 12514268
TI  - Sex and hormonal status modulate the effects of psyllium on plasma lipids and
      monocyte gene expression in humans.
AB  - Psyllium (PSY) intake decreases plasma LDL cholesterol (LDL-C) in men and pre-
      and post-menopausal women while PSY effects on plasma triglycerides (TG) are sex
      related. A significant decrease in plasma TG was observed in men while
      postmenopausal women experienced an increase in plasma TG concentrations
      following PSY supplementation. To further explore the mechanisms by which sex and
      hormonal status influence the effects of PSY on plasma lipids, HMG-CoA reductase,
      LDL receptor and lipoprotein lipase (LPL) mRNA abundance were measured in
      mononuclear cells isolated from these subjects. The intervention followed a
      randomized crossover design in which participants were allocated to either 15 or
      0 g (control) of PSY/d for 30 d. Compared to the control period, PSY intake
      induced a 20% increase in HMG-CoA reductase mRNA abundance (P < 0.05) while no
      significant changes in LDL receptor mRNA abundance were observed. In contrast,
      LPL mRNA abundance was 24% higher in men and 23% lower in postmenopausal women (P
      < 0.05) when comparing PSY with the control period. These results suggest that
      the LDL-C lowering induced by PSY was related to changes in HMG-CoA reductase
      gene expression in monocytes while the expression of LPL in this system was
      affected by sex and hormonal status.

PMID- 12514269
TI  - Expression of DNase I in rat parotid gland and small intestine is regulated by
      starvation and refeeding.
AB  - DNase I in rats is mainly expressed in the parotid gland and the small intestine
      and functions as a digestive enzyme. Male Wistar rats were deprived of food for
      48 h, refed with nonpurified diet for 2 h and killed at 0, 0.33, 0.67, 1, 2, 6 or
      12 h. The activity and mRNA of DNase I in the parotid gland and the small
      intestine were determined. We found that in rats that were not fed for 48 h there
      was accumulation of DNase I in the parotid gland but not in the small intestine.
      In the parotid gland, refeeding decreased DNase I activity (P < 0.05), perhaps
      due to an increase in secretion. The increase in DNase I mRNA probably resulted
      from the need for protein synthesis. However, in the small intestine, both the
      enzyme activity and the amount of mRNA were up-regulated by refeeding (P < 0.05).
      Exposing rats to food in a sealed transparent flask also caused a 2.5-fold
      increase in DNase I mRNA within 30 min in the parotid gland. These data suggested
      that the expression of rat parotid DNase I is up-regulated by feeding and that
      mastication is not essential for the regulation.

PMID- 12514270
TI  - The H475Y polymorphism in the glutamate carboxypeptidase II gene increases plasma
      folate without affecting the risk for neural tube defects in humans.
AB  - In the diet, folate exists predominantly in the form of polyglutamates. Before
      absorption, these polyglutamates must be deconjugated to monoglutamates by the
      enzyme folylpoly-gamma-glutamate carboxypeptidase (FGCP), which is located in the
      jejunum. Recently, a H475Y polymorphism in the glutamate carboxypeptidase II
      (GCPII) gene, encoding the FGCP enzyme, was reported to be associated with
      decreased plasma folate and increased plasma homocysteine (tHcy) levels. Low
      folate and elevated tHcy levels are risk factors for neural tube defects (NTD).
      Therefore, we examined whether this polymorphism is associated with NTD risk and
      plasma folate, erythrocyte folate and plasma tHcy levels in 96 NTD patients, 113
      mothers, 97 fathers and 101 controls. This variation was associated with
      increased plasma folate (P < 0.04) and tended to be associated with decreased
      plasma tHcy (P < 0.09). It was not associated with erythrocyte folate or the risk
      for NTD. The H475Y polymorphism in the GCPII gene may increase the deconjugation
      activity of the FGCP enzyme, resulting in an increased absorption of folate in
      the body, as reflected by the increased plasma folate and decreased plasma
      homocysteine concentrations.

PMID- 12514271
TI  - The serum LDL/HDL cholesterol ratio is influenced more favorably by exchanging
      saturated with unsaturated fat than by reducing saturated fat in the diet of
      women.
AB  - We compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA
      diet, polyunsaturated/saturated fatty acid (P/S) ratio = 0.14], a low fat diet
      (19.7 E% from fat; LSAFA diet, P/S = 0.17), both based on coconut oil, and a diet
      with a high content of mono- and polyunsaturated fatty acids (PUFA; 38.2 E% from
      fat; HUFA diet, P/S = 1.9) on serum lipoproteins. The 25 women studied consumed
      each diet for 3-wk periods in a crossover design. The two high fat diets were
      identical except for the quality of the test fat. The LSAFA diet was identical to
      the HSAFA diet except that half the fat was replaced by carbohydrates. Serum
      total cholesterol, LDL cholesterol and apoB concentrations did not differ between
      the HSAFA and the LSAFA diet periods. Total cholesterol, LDL cholesterol and apoB
      were lower when women consumed the HUFA diet than when they consumed the other
      two diets. HDL cholesterol and apoA-I were 15 and 11%, respectively, higher when
      women consumed the HSAFA diet than when they consumed the LSAFA diet; HDL
      cholesterol and apoA-I were lower when women consumed the HUFA diet than when
      they consumed the HSAFA diet, but not the LSAFA diet. The LDL cholesterol/HDL
      cholesterol and apoB/apoA-I ratios were higher when women consumed the LSAFA diet
      than when they consumed the HSAFA diet. The LDL/HDL cholesterol ratio was higher
      when women consumed either the LSAFA or the HSAFA diet than when they consumed
      the HUFA diet, whereas apoB/apoA-I was higher when women consumed the LSAFA diet
      than when they consumed the HUFA diet. Triacylglycerol and VLDL cholesterol were
      higher when women consumed the LSAFA diet than when they consumed either the
      HSAFA or the HUFA diet. We conclude that, to influence the LDL/HDL cholesterol
      ratio, changing the proportions of dietary fatty acids may be more important than
      restricting the percentage of total or saturated fat energy, at least when
      derived mainly from lauric and myristic acids, both of which increase HDL
      cholesterol.

PMID- 12514272
TI  - Carnitine and choline supplementation with exercise alter carnitine profiles,
      biochemical markers of fat metabolism and serum leptin concentration in healthy
      women.
AB  - We sought to determine the effects of supplementary choline, carnitine and a
      combination of the two with or without exercise on serum and urinary carnitine
      and biochemical markers of fatty acid oxidation in healthy humans. Nineteen women
      were placed in three groups: 1) placebo, choline or carnitine preloading period
      of 1 wk followed by 2) supplementation with choline plus carnitine during wk 2-wk
      3 and 3) all groups exercised in wk 3. Although there were no changes in the
      placebo group, serum and urinary carnitine decreased in the choline-supplemented
      group during wk 1. Introduction of carnitine to the choline group restored serum
      and urinary carnitine. Serum and urinary carnitine increased during wk 1 in the
      carnitine-supplemented group and, although the introduction of choline to this
      group depressed serum and urinary carnitine, they remained significantly greater
      than control. Serum beta-hydroxybutyrate and serum as well as urinary
      acetylcarnitine were elevated by the supplements. A mild exercise regimen
      increased the concentration of serum beta-hydroxybutyrate, and serum and urinary
      acylcarnitines; it also decreased serum leptin concentrations in all groups. The
      effects of supplements were sustained until wk 2 after cessation of choline plus
      carnitine supplementation and exercise. We conclude that the choline-induced
      decrease in serum and urinary carnitine is buffered by carnitine preloading, and
      these supplements shift tissue partitioning of carnitine that favors fat
      mobilization, incomplete oxidation of fatty acids and disposal of their carbons
      in urine as acylcarnitines in humans.

PMID- 12514273
TI  - Two polyol, low digestible carbohydrates improve the apparent absorption of
      magnesium but not of calcium in healthy young men.
AB  - The effects of nondigestible oligosaccharides including polyols on intestinal
      mineral absorption have been studied extensively in animal experiments, but their
      impact on mineral absorption in humans remains to be established. We investigated
      the effects of feeding two fermentable, low digestible carbohydrates, on the
      apparent absorption and balance of calcium (Ca) and magnesium (Mg) in humans.
      Nine healthy young men were given a control diet with dextrose or polyols, low
      digestible, fermentable carbohydrates (LHBC, HPFL) for 32-d periods according to
      a 3 x 3 Latin-square design. During the 18-d period of adaptation, the products
      were administered gradually in liquid form, up to a maximum of 100 g/d, which was
      then consumed for 14 d. Ca and Mg levels were measured in diets and in fecal and
      urine collections to assess apparent mineral absorption and balance. The relative
      apparent absorptions of Ca and Mg from the control diet were (means +/- SEM) 33.3
      +/- 4.6 and 39.8 +/- 2.7%, respectively. Ingestion of both low digestible
      carbohydrates significantly increased the relative apparent absorption of Mg by
      about 25%. LHBC, but not HPFL, ingestion increased urinary Mg excretion. Apparent
      absorption, urinary excretion and balance of Ca were not altered by the ingestion
      of either low digestible carbohydrate. Ingestion of the low digestible,
      fermentable carbohydrates, with balanced diets, improved apparent Mg absorption
      without significant effects on apparent absorption or retention of Ca in healthy
      young men. Further human studies are therefore still needed to confirm the
      effects of these products in other populations.

PMID- 12514274
TI  - Increasing the cooking temperature of meat does not affect nonheme iron
      absorption from a phytate-rich meal in women.
AB  - The effect of increasing cooking temperatures of meat on nonheme iron absorption
      from a composite meal was investigated. Cysteine-containing peptides may have a
      role in the iron absorption enhancing effect of muscle proteins. Heat treatment
      can change the content of sulfhydryl groups produced from cysteine and thereby
      affect iron absorption. Twenty-one women (25 +/- 3 y) were served a basic meal
      without meat and two other meals consisting of the basic meal plus 75 g of pork
      meat cooked at 70, 95 or 120 degrees C. The meals were extrinsically labeled with
      (55)Fe or (59)Fe. Iron absorption was determined from measurements of whole-body
      (59)Fe retention and the activity of (55)Fe and (59)Fe in blood samples. Nonheme
      iron absorptions were 0.9 (0.5-4.0)% (P = 0.06), 0.7 (0.4-3.9)% (P = 0.1) and 2.0
      (1.3-3.1)% (P < 0.001) greater when meat cooked at 70, 95 or 120 degrees C,
      respectively, was added to the basic meal. Increasing the cooking temperature of
      meat did not impair nonheme iron absorption compared with cooking at 70 degrees
      C. Because the cysteine content of meat decreased with increasing cooking
      temperature, this argues against a specific contribution of sulfhydryl groups
      from cysteine residues in the promotion of nonheme iron absorption by meat
      proteins.

PMID- 12514275
TI  - Supplementation with beta-carotene or a similar amount of mixed carotenoids
      protects humans from UV-induced erythema.
AB  - Carotenoids are useful oral sun protectants, and supplementation with high doses
      of beta-carotene protects against UV-induced erythema formation. We compared the
      erythema-protective effect of beta-carotene (24 mg/d from an algal source) to
      that of 24 mg/d of a carotenoid mix consisting of the three main dietary
      carotenoids, beta-carotene, lutein and lycopene (8 mg/d each). In a placebo
      controlled, parallel study design, volunteers with skin type II (n = 12 in each
      group) received beta-carotene, the carotenoid mix or placebo for 12 wk.
      Carotenoid levels in serum and skin (palm of the hand), as well as erythema
      intensity before and 24 h after irradiation with a solar light simulator were
      measured at baseline and after 6 and 12 wk of treatment. Serum beta-carotene
      concentration increased three- to fourfold (P < 0.001) in the beta-carotene
      group, whereas in the mixed carotenoid group, the serum concentration of each of
      the three carotenoids increased one- to threefold (P < 0.001). No changes
      occurred in the control group. The intake of either beta-carotene or a mixture of
      carotenoids similarly increased total carotenoids in skin from wk 0 to wk 12. No
      changes in total carotenoids in skin occurred in the control group. The intensity
      of erythema 24 h after irradiation was diminished in both groups that received
      carotenoids and was significantly lower than baseline after 12 wk of
      supplementation. Long-term supplementation for 12 wk with 24 mg/d of a carotenoid
      mix supplying similar amounts of beta-carotene, lutein and lycopene ameliorates
      UV-induced erythema in humans; the effect is comparable to daily treatment with
      24 mg of beta-carotene alone.

PMID- 12514276
TI  - Intakes of calcium and vitamin d predict body mass index in the population of
      Northern Norway.
AB  - This study was designed to investigate whether there is any association between
      body mass index (BMI) and life-style factors, with a special emphasis on calcium
      and vitamin D intakes. In 1994/1995, men (n = 9252) and women (n = 9662)
      participated in the fourth Tromso study and completed the food-frequency and life
      style factor questionnaires. We measured BMI, coffee and alcohol consumption,
      physical activity, smoking, and calcium and vitamin D intakes. A negative
      association between physical activity, smoking and BMI, and a positive
      association between BMI and coffee intake were found in both sexes (P < 0.001).
      BMI and calcium intake were positively related in men (P < 0.001), but not in
      women. BMI and vitamin D intake were negatively associated in both sexes (P <
      0.001), which to our knowledge has not been reported before. The lowest quartile
      of vitamin D intake was an independent predictor of obesity (defined as BMI >30
      kg/m(2)) in men and women (P < 0.001 in both genders), resulting in odds ratios
      of 2.24 [95% confidence interval (CI) 1.80, 2.80] in men and 1.51 (95% CI 1.23,
      1.85) in women compared with the highest quartile. In conclusion, calcium and
      vitamin D intakes may have opposing effects on body weight, which is difficult to
      explain given current knowledge of calcium metabolism.

PMID- 12514277
TI  - Changes in child survival are strongly associated with changes in malnutrition in
      developing countries.
AB  - Considerable evidence suggests that malnutrition affects human performance,
      health and survival, including physical growth, morbidity, mortality, cognitive
      development, reproduction, physical work capacity and risks for several adult
      onset chronic diseases. In recent decades, development agencies and governments
      have emphasized selective interventions to improve health and nutritional status,
      such as immunizations, oral rehydration, antibiotics and micronutrients, with
      child survival as a major motivation and justification. Although the efficacy of
      these approaches for improving child survival has been amenable to study,
      providing some of the rationale for using these approaches, it has not been
      possible to test directly the effects of improvements in general malnutrition.
      The present study quantified the effects of changes in general malnutrition, as
      measured by child weight-for-age (WA), on changes in child survival in 59
      developing countries, using aggregate, longitudinal data at national and
      subnational levels from 1966 to 1996. Mixed model analysis (in SAS) was used, to
      take advantage of the multilevel and longitudinal nature of these data sets.
      Changes in WA have a statistically significant effect on changes in child
      mortality, independent of socioeconomic and policy changes represented by the
      secular trend. The secular trend in mortality began earlier and leveled off at
      higher mortality rates in populations with a higher prevalence of malnutrition.
      Gaps in coverage of selective interventions are more likely and more serious in
      the more malnourished populations. Continued reduction in mortality will require
      improved targeting of selective interventions and general nutritional improvement
      to the most marginal populations.

PMID- 12514278
TI  - Household food insufficiency is associated with poorer health.
AB  - The purposes of this study were to estimate the prevalence of household food
      insufficiency in Canada, to identify sociodemographic characteristics of
      households most likely to report food insufficiency and to examine the
      relationship between food insufficiency and physical, mental and social health.
      These objectives were achieved through an analysis of data from the 1996/1997
      National Population Health Survey. An estimated 4% of Canadians, 1.1 million
      people, were found to be living in food-insufficient households. Single-parent
      families, households reporting their major source of income as welfare,
      unemployment insurance or workers' compensation, those who did not own their own
      homes and households in Western Canada were more likely to report food
      insufficiency. The likelihood of reporting food insufficiency increased
      dramatically as income adequacy deteriorated. Individuals from food-insufficient
      households had significantly higher odds of reporting poor/fair health, of having
      poor functional health, restricted activity and multiple chronic conditions, of
      suffering from major depression and distress, and of having poor social support.
      Individuals in food-insufficient households were also more likely to report heart
      disease, diabetes, high blood pressure and food allergies. Men in food
      insufficient households were less likely to be overweight; after adjusting for
      potentially confounding variables, no other associations were found between food
      insufficiency and body mass index. These findings suggest that food insufficiency
      is one dimension of a more pervasive vulnerability to a range of physical, mental
      and social health problems among households struggling with economic constraints.

PMID- 12514279
TI  - Muscle lipid metabolism and insulin secretion are altered in insulin-resistant
      rats fed a high sucrose diet.
AB  - Feeding rats a sucrose rich diet (SRD) induces hypertriglyceridemia and insulin
      resistance. The purposes of this study were to determine the time course of
      changes in lipid and glucose metabolism in the gastrocnemius muscle, both in the
      basal state and after the euglycemic hyperinsulinemic clamp, in rats fed a SRD
      for 3, 15 or 30 wk, and to analyze the changes in glucose-stimulated insulin
      secretion from perifused isolated islets from SRD-fed rats and their
      relationships to peripheral insulin insensitivity. A control group of rats was
      fed a control diet (CD) for the same period of time. After 3 wk of consuming the
      SRD, long-chain acyl CoA (LCACoA) levels in muscle were greater than in rats fed
      the CD, an early indication of the disturbance of lipid metabolism. Neither
      glycogen storage nor glucose oxidation were impaired at this time. Moreover, the
      biphasic patterns of glucose-stimulated insulin secretion showed a marked
      increase in the first peak, which helped maintain normoglycemia in SRD-fed rats.
      After 15 or 30 wk of consuming the SRD, triglyceride and LCACoA levels in muscles
      were greater than in rats fed the CD. Glucose oxidation as well as insulin
      stimulated glycogen synthase activity and glycogen storage were lower than in
      rats fed the CD. Moreover, the altered pattern of insulin secretion further
      deteriorated. This was accompanied by peripheral insulin resistance and moderate
      hyperglycemia. Our results indicate that the dyslipemia present in rats
      chronically fed a SRD may play an important role in the progressive deterioration
      of insulin secretion and sensitivity in this animal model.

PMID- 12514280
TI  - Consumption of raw potato starch increases colon length and fecal excretion of
      purine bases in growing pigs.
AB  - Male growing pigs were fed a diet containing 250 g/kg of native corn starch (CS;
      26% amylose, 74% amylopectin) or 250 g/kg of raw potato starch (RPS), as examples
      of digestible starch and resistant starch (Type II), respectively. Whole-tract
      digestibilities of organic matter, crude protein and starch were greater in pigs
      fed CS than in those fed RPS through at least d 23 of the study. However, the
      values progressively increased in the RPS-fed pigs up to d 38, at which time the
      groups did not differ in organic matter and starch digestibility. The digestive
      tract and colonic digesta were heavier and colon length longer in pigs fed the
      RPS diet. Digestibility of starch in the ileum on d 38 was significantly lower in
      RPS-fed pigs, but rose from ileum to rectum; most starch was extensively
      fermented in the cecum and proximal colon. Purine base (PB) and short-chain fatty
      acid (SCFA) concentrations in feces initially increased and then decreased
      beginning on d 4 for PB and on d 21 for SCFA. PB concentration in feces was
      greater in pigs fed RPS than in those fed CS. In the large bowel digesta, PB and
      SCFA concentrations increased from the ileum to the cecum and proximal colon and
      then fell in the distal colon. Pigs fed the RPS diet had a higher PB
      concentration in the middle colonic digesta and a greater SCFA concentration in
      the proximal colonic digesta than the CS-fed group. Adaptation of growing pigs to
      supplementary RPS required 5 wk, as reflected by whole-tract digestibility and PB
      and SCFA fecal excretion data.

PMID- 12514281
TI  - Early postnatal food intake alters myofiber maturation in pig skeletal muscle.
AB  - We examined the effects of undernutrition on muscle development during the first
      postnatal week in pigs. Eighteen piglets were subjected to three nutritional
      levels (300, 200 or 100 g/(kg body. d) of colostrum then milk) between birth and
      slaughter at 7 d of age. Longissimus lumborum (LL), a fast-twitch glycolytic
      muscle, and rhomboideus (RH), a mixed slow- and fast-twitch oxido-glycolytic
      muscle, were taken for myofiber typing and biochemical analyses. Enzyme
      activities of lactate dehydrogenase (LDH), citrate synthase (CS) and beta-hydroxy
      acyl-CoA-dehydrogenase (HAD) were used as markers of glycolytic, oxidative and
      lipid beta-oxidation capacities, respectively. Undernutrition selectively
      decreased (P < 0.001) hypertrophy of the future fast-twitch glycolytic fibers in
      LL. Contractile and metabolic maturation was delayed in the later maturing LL, as
      reflected by a decrease in muscle protein concentration (P < 0.01), an increase
      (P < 0.05) in the percentage of myofibers still expressing the fetal myosin heavy
      chain (MyHC), a lower postnatal increase in LDH activity (P < 0.001) and a
      delayed decrease in the percentage of IIa MyHC positive fibers (P < 0.001).
      Otherwise, restriction tended (P < 0.10) to increase the percentage of slow type
      I MyHC containing fibers in both muscles and of alpha-cardiac MyHC positive
      fibers in RH (P < 0.05). The LDH/CS ratio decreased dramatically (P < 0.001)
      after restriction, to a greater extent in LL than in RH. These changes denoted a
      more oxidative metabolism using fewer carbohydrates and more lipids in restricted
      pigs, as suggested by the increased activity of HAD (P < 0.001) and decreased
      respiratory quotient (P < 0.001).

PMID- 12514282
TI  - Absorption and conversion of 11,12-(3)H-beta-carotene to vitamin A in Sprague
      Dawley rats of different vitamin A status.
AB  - The aim of this study was to determine the bioavailability and bioconversion to
      vitamin A of a single oral dose in oil or an aqueous dispersion of labeled beta
      carotene in rats of different vitamin A status. Weanling Sprague-Dawley rats were
      fed a vitamin A-deficient diet and supplemented for 4 wk with 0, 7, 21 and 63
      micro g/(rat. d) of retinyl acetate. The rats, of different vitamin A status,
      were then given a single oral dose of 11,12-(3)H-beta-carotene (0.15 micro mol)
      dissolved in corn oil or dispersed in aqueous Tween 80. The rats were killed 4 or
      24 h after the dose, and serum, liver, the entire digestive tract, other tissues,
      urine and feces were analyzed for carotenoids, retinoids and associated
      radioactivity. At 4 h after the dose, 85 +/- 9% of the administered radioactivity
      was recovered. Almost 50% of the dose was present as intact beta-carotene in the
      large intestine where further absorption and conversion was ruled out. The
      absorption of beta-carotene was very low, and < 5% of the radioactive dose was
      converted to retinoids. The absorption and conversion to vitamin A did not differ
      among rats of different vitamin A status. The results suggest that a single oral
      dose of beta-carotene might not be an effective way of raising vitamin A stores
      in the body.

PMID- 12514283
TI  - Iron bioavailability and utilization in rats are lower from lime-treated corn
      flour than from wheat flour when they are fortified with different sources of
      iron.
AB  - Although iron bioavailability from wheat flour fortified with iron has been
      widely studied, the bioavailability of lime-treated corn flour has not been
      evaluated sufficiently. We compared iron bioavailability and utilization of lime
      treated corn flour and wheat flour supplemented with various iron sources.
      Bioavailability and utilization were determined in Sprague-Dawley rats using the
      iron balance and hemoglobin depletion-repletion methods. Rats were iron depleted
      by feeding them a low iron, casein diet for 10 d. During the repletion period,
      the rats were fed diets based on lime-treated corn flour or wheat flour, both
      supplemented with ferrous fumarate, ferrous sulfate, ferric citrate and reduced
      iron for 14 d. Hemoglobin was determined at the end of depletion and repletion
      periods. The phytate concentration was lower in wheat flour (114 mg/100g) than in
      lime-treated corn flour (501 mg/100g). Iron bioavailability and utilization by
      rats were higher from fortified and unfortified wheat flour than from the lime
      treated corn flour counterparts. Iron utilization was greater in rats fed wheat
      flour supplemented with ferrous sulfate, followed by fumarate and citrate than in
      rats fed reduced iron. In lime-treated corn flour, iron utilization by rats fed
      unfortified flour and flour fortified with reduced iron did not differ, but
      utilization was higher in rats fed corn flour fortified with iron sulfate,
      fumarate and citrate than with reduced iron. We conclude that fortification of
      lime-treated corn flour with reduced iron has no effect on iron bioavailability
      or utilization, probably due to the high phytate content. Other iron compounds
      must be selected to fortify lime-treated corn flour when intended for public
      nutrition programs.

PMID- 12514284
TI  - Serum concentrations of lipids, vitamin d metabolites, retinol, retinyl esters,
      tocopherols and selected carotenoids in twelve captive wild felid species at four
      zoos.
AB  - Serum concentrations of several nutrients were measured in 12 captive wild felid
      species including caracal (Felis caracal), cheetah (Acinonyx jubatus), cougar
      (Felis concolor), fishing cat (Felis viverrinus), leopard (Panthera pardus), lion
      (Panthera leo), ocelot (Felis pardalis), pallas cat (Felis manul), sand cat
      (Felis margarita), serval (Felis serval), snow leopard (Panthera uncia) and tiger
      (Panthera tigris). Diet information was collected for these animals from each
      participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological
      Gardens and North Carolina Zoological Park). The nutritional composition of the
      diets at each institution met the probable dietary requirements for each species
      except for the pallas cat. Blood samples were collected from each animal (n = 69)
      and analyzed for lipids (total cholesterol, triacylglycerides, HDL cholesterol
      and LDL cholesterol), vitamin D metabolites [25-hydroxycholecalciferol (25(OH)D)
      and 1,25-dihydroxycholecalciferol (1,25(OH)(2)D)], vitamin A (retinol, retinyl
      stearate and retinyl palmitate), vitamin E (alpha- and gamma-tocopherol) and
      selected carotenoids. Species differences were found for all except
      triacylglycerides and 1,25(OH)(2)D. Genus differences were found for retinol,
      retinyl palmitate, retinyl stearate, gamma-tocopherol and beta-carotene.
      Circulating nutrient concentrations for many of the species in this study have
      not been reported previously and most have not been compared with the animals'
      dietary intakes. The large number of animals analyzed provides a substantial base
      for comparing the serum nutrient concentrations of healthy animals, for both wild
      and captive exotic species.

PMID- 12514285
TI  - Inevitable iron loss by human adolescents, with calculations of the requirement
      for absorbed iron.
AB  - In growing individuals, the requirement for absorbed iron consists of iron needed
      for growth and iron needed to replace inevitable iron loss. We were able to
      estimate inevitable iron loss by adolescents because total body iron of the
      adolescents had been enriched with the stable isotope, (58)Fe, as the result of
      earlier studies of iron absorption. During an interval beginning at least 1.56 y
      after isotope administration (a time sufficient for complete mixing of the
      isotope with total body iron) and extending for no less than 3.29 y, we
      determined the isotopic enrichment of circulating iron. On the basis of several
      assumptions, we calculated total body (58)Fe and total body iron at the beginning
      and end of the interval. Because of complete mixing of the isotope with total
      body iron, fractional total (58)Fe loss was the same as fractional loss of total
      iron. In males, the fractional loss of iron was 9.70%/y and the quantitative loss
      was 256 mg/y or 0.70 mg/d. In females, the fractional loss of iron was 14.60%/y
      and the quantitative loss was 306 mg/y or 0.84 mg/d. Using several assumptions,
      we then calculated that the iron requirement for growth during this interval was
      0.76 mg/d for males and 0.31 mg/d for females. Adding the iron loss to the iron
      requirement for growth, the requirement for absorbed iron was estimated to be
      1.46 mg/d for males and 1.15 mg/d for females.

PMID- 12514286
TI  - Exposing ferrets to cigarette smoke and a pharmacological dose of beta-carotene
      supplementation enhance in vitro retinoic acid catabolism in lungs via induction
      of cytochrome P450 enzymes.
AB  - In our previous studies, we found lower levels of retinoic acid (RA) in the lungs
      of ferrets exposed to cigarette smoke and/or a pharmacological dose of beta
      carotene. To determine whether this is involved in excessive catabolism of RA via
      cytochrome P450 (CYP) induction, we carried out in vitro incubations of RA with
      the lung microsomal fractions of ferrets with or without CYP inhibitors and
      antibodies against CYP. The polar metabolites (4-oxo-RA and 18-hydroxy-RA) of RA
      metabolism after the incubation were analyzed by HPLC. Expressions of CYP (1A1,
      1A2, 2E1 and 3A1) were examined using Western blot analysis. Incubation of
      various concentrations of RA with the lung microsomal fraction from ferrets
      exposed to cigarette smoke, a pharmacological dose of beta-carotene or their
      combination dose-dependently increased the levels of 4-oxo-RA and 18-hydroxy-RA
      compared with that of the control ferrets. At all RA concentrations, this
      increase was the greatest in lung tissue from the combined treatment group.
      Furthermore, this enhanced RA catabolism was substantially (approximately 80%)
      inhibited by nonspecific CYP inhibitors (disulfiram and liarozole), but was
      partially (approximately 50%) inhibited by resveratrol (CYP1A1 inhibitor), alpha
      naphthoflavone (CYP1A2 inhibitor) and antibodies against CYP1A1 and CYP1A2.
      Cigarette smoke exposure and/or pharmacological doses of beta-carotene increased
      levels of CYP1A1 and 1A2 by three- to sixfold but not levels of 2E1 and 3A1 in
      ferret lung tissue. These findings suggest that low levels of RA in the lung of
      ferrets exposed to cigarette smoke and/or pharmacological doses of beta-carotene
      may be caused by the enhanced RA catabolism via induction of CYP, CYP1A1 and
      CYP1A2 in particular, which provides a possible explanation for enhanced lung
      carcinogenesis seen with pharmacological doses of beta-carotene supplementation
      in cigarette smokers.

PMID- 12514287
TI  - Detrimental effects of a high fat diet in early renal injury are ameliorated by
      fish oil in Han:SPRD-cy rats.
AB  - Dietary fish oils containing (n-3) fatty acids can modulate renal inflammatory
      injury. We previously demonstrated that a high fat (HF) diet worsens early renal
      disease progression in the Han:SPRD-cy rat model of polycystic kidney disease
      (PKD). Therefore, using HF (20 g/100 g diet) and low fat (LF; 5 g/100 g diet)
      diets, we compared the effects of menhaden oil (MO), soybean oil (SO) and
      cottonseed oil (CO) on renal function and histology in male Han:SPRD-cy rats fed
      the diets for 6 wk in the early stages of renal disease. Overall, rats fed HF
      compared with those fed LF diets had larger kidneys, more renal fibrosis and
      lower creatinine clearance (main effects of fat level). Rats fed MO rather than
      CO and SO diets had significantly lower kidney weights, kidney water content,
      cyst volumes and serum cholesterol and triglyceride concentrations (main effects
      of fat type). Rats fed MO diets also had less renal fibrosis than those fed CO
      diets, but the least fibrosis was in rats fed SO diets. Analysis of simple
      effects (due to interactions between fat level and type) revealed that HF diets
      increased renal inflammation in rats fed CO diets, but reduced inflammation was
      present in those fed SO and MO diets; HF diets also increased compared with LF
      diets serum urea nitrogen concentrations in rats fed the MO and CO diets, but not
      the SO diet. These results confirm that high dietary fat worsens early disease
      progression in this model of renal disease, and further demonstrate that diets
      with oils containing (n-3) fatty acids ameliorate some of the detrimental effects
      of a high fat diet.

PMID- 12514288
TI  - Dahl salt-sensitive rats excrete 25-hydroxyvitamin D into urine.
AB  - The plasma 25-hydroxyvitamin D concentration of Dahl salt-sensitive rats (S) is
      markedly decreased in response to high sodium chloride (salt) intake. We tested
      the hypothesis that urinary excretion is a mechanism for the decrease. Female S
      rats excreted 0.26 +/- 0.04 nmol 25-hydroxyvitamin D/24 h at wk 2 of high salt
      (80 g/kg) intake, five times that of female salt-resistant (R) rats at wk 2 of
      high salt intake and nine times that of S rats at wk 2 of low salt (3 g/kg)
      intake. The 25-hydroxyvitamin D binding activity in 24-h urine of S rats was 79
      +/- 11 pmol/h at wk 2 of high salt intake, two times that in urine of S rats at
      wk 2 of low salt intake and > 35 times that in urine of R rats at wk 2 of low or
      high salt intake. We conclude that markedly decreased plasma 25-hydroxyvitamin D
      concentrations of S rats during high salt intake result in part from excretion of
      protein-bound 25-hydroxyvitamin D. Low plasma 25-hydroxyvitamin D concentrations
      in humans may also result in part from salt sensitivity, which is prevalent in >
      50% of the United States hypertensive population.

PMID- 12514289
TI  - Zinc deficiency suppresses the development of oral tolerance in rats.
AB  - Oral tolerance is a specific immune unresponsiveness to food antigens to prevent
      hypersensitivity reactions. We investigated whether zinc deficiency affects oral
      tolerance. Rats were fed a control (C) or zinc-deficient (ZD) diet, or pair-fed
      (PF) to ZD rats for 28 d. Beginning on d 7, rats were administered ovalbumin
      (OVA) orally to induce tolerance, or PBS 3 times/wk, and were then immunized by
      OVA injection. The proliferation of mesenteric lymph node (MLN) and spleen
      lymphocytes after in vitro OVA stimulation and the delayed-type hypersensitivity
      were higher in OVA-fed ZD than in OVA-fed C rats and not different between OVA-
      and PBS-fed ZD rats, indicating a suppression of tolerance. Lymphocyte
      proliferation did not differ between PF and C rats. Expressions of cytokines
      involved in oral tolerance, i.e., interleukin (IL)-4, IL-10 and transforming
      growth factor-beta, were higher in OVA- than in PBS-fed C rats, but not in ZD
      rats. Apoptosis was higher in OVA- than in PBS-fed C rats but not different
      between OVA- and PBS-fed ZD rats. Inflammation and ulcerations that were not
      present in ZD rats on d 7 (ZD(7)) developed in OVA- or PBS-fed ZD rats. Compared
      with ZD(7) rats, tumor necrosis factor-alpha and cytokine-induced neutrophil
      chemoattractant were higher in OVA- and PBS-fed ZD rats, whereas interferon-gamma
      increased only in OVA-fed ZD rats. In conclusion, zinc deficiency suppresses oral
      tolerance through dysregulation of cytokine expression and lack of antigen
      specific clonal deletion. We suggest that abrogation of tolerance may lead to
      development of mucosal inflammation and damage.

PMID- 12514290
TI  - Low intake of fruits, berries and vegetables is associated with excess mortality
      in men: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.
AB  - Diets rich in fruits and vegetables have been of interest because of their
      potential health benefits against chronic diseases such as cardiovascular disease
      (CVD) and cancer. The aim of this work was to assess the association of the
      dietary intake of a food group that includes fruits, berries and vegetables with
      all-cause, CVD-related and non-CVD-related mortality. The subjects were Finnish
      men aged 42-60 y examined in 1984-1989 in the prospective Kuopio Ischaemic Heart
      Disease Risk Factor (KIHD) Study. Dietary intakes were assessed by 4-d food
      intake record during the baseline phase of the KIHD Study. The risk of all-cause
      and non-CVD-related deaths was studied in 2641 men and the risk of CVD-related
      death in 1950 men who had no history of CVD at baseline. During a mean follow-up
      time of 12.8 y, cardiovascular as well as noncardiovascular and all-cause
      mortality were lower among men with the highest consumption of fruits, berries
      and vegetables. After adjustment for the major CVD risk factors, the relative
      risk for men in the highest fifth of fruit, berry and vegetable intake for all
      cause death, CVD-related and non-CVD-related death was 0.66 [95% confidence
      interval (CI) 0.50-0.88], 0.59 (0.33-1.06), and 0.68 (0.46-1.00), respectively,
      compared with men in the lowest fifth. These data show that a high fruit, berry
      and vegetable intake is associated with reduced risk of mortality in middle-aged
      Finnish men. Consequently, the findings of this work indicate that diets that are
      rich in plant-derived foods can promote longevity.

PMID- 12514291
TI  - Lactation counseling increases breast-feeding duration but not breast milk intake
      as measured by isotopic methods.
AB  - The importance of exclusive breast-feeding in the first 6 mo of life is widely
      recognized, but most mothers still do not reach this goal. Several studies have
      shown that face-to-face lactation counseling is effective in increasing not only
      exclusive breast-feeding rates but also the total duration of breast-feeding.
      However, it is unclear whether counseling could increase breast milk intake. The
      purpose of this study was to evaluate the effect of lactation counseling on
      breast milk intake, assessed through the deuterium dilution method. This was a
      blind, randomized intervention trial of lactation counseling in a sample of 188
      babies born in Pelotas, selected with the same criteria used for the WHO
      Multicentre Growth Reference Study (MGRS). The main outcomes were breast-feeding
      pattern and duration for all infants as well as breast milk intake for a
      subsample of 68 infants at the age of 4 mo. Mothers in the control group were
      almost twice as likely to stop breast-feeding by 4 mo as those in the
      intervention group (prevalence ratio 1.85; P = 0.04). Cox regression confirmed
      that the velocity of weaning was twice as high in the control group. Breast milk
      and total water intakes did not differ between the groups. The deuterium dilution
      technique proved to be a practical means of assessing breast milk intake.
      Lactation counseling reduced early weaning, but breast milk intake at 4 mo was
      not affected.

PMID- 12514292
TI  - Regional variations of blood pressure in the United States are associated with
      regional variations in dietary intakes: the NHANES-III data.
AB  - Compared with other regions in the United States, the southern region has had the
      highest stroke mortality rate and a more prevalent and resistant hypertension. We
      designed this analysis of the data obtained from the National Health and
      Nutritional Examination Survey III (NHANES-III), which is a community-based cross
      sectional survey, to describe regional variations in blood pressure and the
      reported consumption of nutrients, focusing on those linked to blood pressure, in
      the United States. We selected the following variables from the NHANES-III data
      for this analysis: systolic and diastolic blood pressures, protein,
      carbohydrates, total fatty acids, saturated fatty acids, monounsaturated fatty
      acids, polyunsaturated fatty acids, cholesterol, fiber, sodium, potassium,
      calcium, magnesium, zinc, copper, iron, riboflavin, niacin, thiamin, alcohol and
      vitamins C, E, B-6 and B-12. Of the 17,752 participants in the survey who were 18
      y of age or older, the south had the highest systolic and diastolic blood
      pressures (P < 0.005 for each) and reported the highest consumption of
      monounsaturated fatty acids, polyunsaturated fatty acids and cholesterol (P <
      0.05 for all) and the least amount of fiber in the multivariate analysis (P <
      0.005). The highest reported sodium consumption was in the south region (3.4 +/-
      0.02 g), and the lowest was in the west (3.2 +/- 0.03 g; P < 0.05). The south
      also consumed the least potassium, calcium, phosphorous, magnesium, copper,
      riboflavin, niacin, iron and vitamins A, C and B-6 (P < 0.005). There was no
      difference among the four regions in frequency of "adding salt on the table." The
      region of the United States that includes the "stroke belt" has dietary patterns
      that may contribute to the high prevalence of hypertension and cardiovascular
      disease.

PMID- 12514293
TI  - Acute phase protein levels and thymus, spleen and plasma protein synthesis rates
      differ in adult and old rats.
AB  - Aging induces a dysregulation of immune and inflammation functions that may
      affect protein synthesis rates in lymphoid tissue and plasma proteins. We
      quantified in vivo synthesis rates of thymus, spleen and plasma proteins,
      including albumin and acute phase proteins, in adult (8 mo old) and old (22 mo
      old) rats using the flooding dose method [L-(1-(13)C) phenylalanine].
      Immunosenescence was reflected by thymus atrophy and spleen hypertrophy in old
      rats but not in adult rats. A low albumin plasma level associated with high
      concentrations of fibrinogen, alpha(2)-macroglobulin, alpha(1)-acid glycoprotein
      and proteins other than albumin revealed a low grade inflammation in old rats.
      Protein fractional synthesis rates (FSR) and protein synthesis efficiencies of
      thymus were 29 and 26% lower in old than in adult rats, respectively; these
      variables did not differ in spleen. Protein absolute synthesis rates (ASR) of the
      thymus and spleen were 76% lower and 67% greater in old than adult rats,
      respectively. The FSR and ASR of albumin and other plasma proteins were greater
      in old than in adult rats. Protein synthesis measurement is a valuable
      nonimmunological tool to assess, in vivo, immune and inflammatory variables.
      Alterations in secondary lymphoid organs and plasma protein synthesis may
      contribute to the significant repartitioning of amino acids in old compared with
      adult rats and may be involved in sarcopenia.

PMID- 12514294
TI  - Protein digestibility and quality in products containing antinutritional factors
      are adversely affected by old age in rats.
AB  - The protein digestibility-corrected amino acid score (PDCAAS) has been
      recommended to be the most suitable method for routine evaluation of protein
      quality of foods by FAO/WHO. The PDCAAS method includes the use of young rats for
      predicting protein digestibility of foods for all ages including the elderly. To
      assess the usefulness of protein digestibility in old rats in the calculation of
      PDCAAS for the elderly, the influence of age on the digestibility of protein in 5
      wk-old and 20-mo-old rats by the balance method was studied. Fifteen protein
      products were tested. Each protein product was fed as the sole source of 10%
      dietary protein. A protein-free diet was also included to obtain an estimate of
      metabolic fecal protein. Protein digestibility values (corrected for metabolic
      fecal protein loss) in old rats were significantly (P < 0.05) lower than in young
      rats for most products; however, these differences were small (up to 3%) for
      properly processed animal products (casein, whey protein concentrate, whey
      protein hydrolysate, lactalbumin and skim milk powder). Similarly, the
      differences attributed to age were not large (up to 5%) for properly processed
      vegetable protein products (soy protein isolate and autoclaved soybean meal,
      black beans and fava beans). However, digestibility values in old rats were
      considerably lower (7-17%) than in young rats when fed products containing
      antinutritional factors, that is, mustard flour containing glucosinolates;
      alkaline/heat-treated soy protein isolate and lactalbumin-containing
      lysinoalanine; raw soybean meal and black beans containing trypsin inhibitors;
      and heated skim milk powder containing Maillard compounds. Therefore, the
      inclusion of protein digestibility data obtained using young rats in the
      calculations of PDCAAS may overestimate protein digestibility and quality of
      these products for the elderly. For products specifically intended for the
      elderly, protein digestibility should be determined using old rats.

PMID- 12514295
TI  - Genistein activates p38 mitogen-activated protein kinase, inactivates ERK1/ERK2
      and decreases Cdc25C expression in immortalized human mammary epithelial cells.
AB  - Genistein (4',5,7-trihydroxyisoflavone) is an isoflavonoid present in soybeans
      that exhibits anticarcinogenic effects in breast, colon and prostate cancer
      cells. We recently reported that genistein treatment of the immortalized but
      nonmalignant human mammary epithelial cell line MCF-10F resulted in growth arrest
      of MCF-10F cells in the G2 phase of the cell cycle, a large induction of the
      Tyr15 phosphorylation of Cdc2 (along with decreased activity of Cdc2), increased
      expression of p21(waf/cip1) and decreased expression of the cell cycle
      phosphatase Cdc25C. In the present study of MCF-10F cells, genistein rapidly and
      significantly activated p38, inactivated ERK1/ERK2 and had no effect on SAPK/JNK
      activity. We also showed that p38 is involved in genistein-induced changes in
      Cdc2 phosphorylation and that the downregulation of Cdc25C expression by
      genistein is through the p38 pathway. Finally, we provided evidence that the p38
      pathway is involved in genistein-inhibited cell proliferation. These data suggest
      an important interplay between the p38 pathway and G2 cell cycle checkpoint
      control and provide insights into possible mechanisms whereby this isoflavone may
      inhibit early events in mammary carcinogenesis.

PMID- 12514296
TI  - Implications of day-to-day variability on measurements of usual food and nutrient
      intakes.
AB  - Day-to-day variability in dietary intake makes it difficult to measure accurately
      the "usual" intake of foods and nutrients. The objectives of the present study
      were to estimate within- and between-subject variability for foods and nutrients
      by adjusted and unadjusted models and to assess the number of days required to
      assess nutrient and food group intakes accurately by two different methods. Adult
      men and women aged 18-65 y (n = 1543) in the Food Habits of Canadians Study
      provided a 24-h recall. A repeat interview was conducted in a subsample to
      estimate components of variability. Within- and between-subject variability were
      determined by mixed model procedure (crude and adjusted for age, gender,
      education, smoking, family size and season). The number of days required to
      obtain various degrees of accuracy was ascertained by two methods, one that uses
      the variance ratio for groups and one that considers within-subject variability
      alone for individuals. Variance ratios were higher using the adjusted compared
      with the unadjusted method (e.g., for men, energy 1.07 vs. 0.49). More days were
      required to reflect usual intake with accuracy using the adjusted model (energy 5
      vs. 2 d), indicating the need to control for confounders to obtain reliable
      estimates of intakes.

PMID- 12514297
TI  - Nutrient requirements for preterm infant formulas-molybdenum.

PMID- 12514298
TI  - Do maternal methyl supplements in mice affect DNA methylation of offspring?

PMID- 12514300
TI  - Dairy product components and weight regulation: symposium overview.

PMID- 12514301
TI  - Increased dairy product or calcium intake: is body weight or composition affected
      in humans?
AB  - To assess the possible impact of increased intakes of dairy products or calcium
      on body weight or composition, a MEDLINE search was conducted to identify
      randomized trials of supplementation with calcium or dairy products. Nine studies
      of dairy product supplementation were located: In seven, no significant
      differences in the change in body weight or composition were detected between
      treatment and control groups. However, two studies conducted in older adults
      observed significantly greater weight gain in the dairy product groups. The
      interpretation of these findings is complicated by the inability to accurately
      determine the extent of dietary compensation for the increment in energy intake
      provided by the added dairy products. This is not an issue in the interpretation
      of studies of calcium supplementation, of which 17 were identified. Only one
      study found greater weight loss in the supplemented group; in the remaining
      studies, changes in body weight and/or body fat were strikingly similar between
      groups. In conclusion, the data available from randomized trials of dairy product
      or calcium supplementation provide little support for an effect in reducing body
      weight or fat mass. However, the studies reviewed were not specifically designed
      or powered to address this issue; such studies are required.

PMID- 12514302
TI  - Calcium intake and reduction in weight or fat mass.
AB  - Obesity is a growing epidemic with subsequent health consequences leading not
      only to reduced quality of life but also to increased medical costs. Growing
      evidence supports a relationship between increased calcium intakes and reductions
      in body weight specific to fat mass. Since the first observations in rats >10 y
      ago, several recently published clinical studies support this relationship as
      well. The impact of calcium intake on weight loss or prevention of weight gain
      has been demonstrated in a wide age range of Caucasian and African-Americans of
      both genders. This review focuses on the results of clinical trials that have
      investigated the impact of calcium and dairy products on prevention of weight
      gain, weight loss or development of the insulin resistance syndrome. The
      implications of these results are that calcium may play a substantial
      contributing role in reducing the incidence of obesity and prevalence of the
      insulin resistance syndrome.

PMID- 12514303
TI  - Mechanisms of dairy modulation of adiposity.
AB  - Dietary calcium plays a pivotal role in the regulation of energy metabolism, in
      that we have found high calcium diets to attenuate adipocyte lipid accretion and
      weight gain during periods of overconsumption of an energy-dense diet and to
      increase lipolysis and preserve thermogenesis during caloric restriction, thereby
      markedly accelerating weight loss. Our studies of the agouti gene in obesity and
      insulin resistance demonstrate a key role for intracellular Ca(2+) in regulating
      adipocyte lipid metabolism and triglyceride storage, with increased intracellular
      Ca(2+), resulting in stimulation of lipogenic gene expression and lipogenesis,
      and suppression of lipolysis, resulting in adipocyte lipid filling and increased
      adiposity. Moreover, we have recently demonstrated that the increased calcitriol
      produced in response to low calcium diets stimulates Ca(2+) influx in human
      adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol
      levels by increasing dietary calcium is an attractive target for the prevention
      and management of obesity. In support of this concept, transgenic mice expressing
      the agouti gene specifically in adipocytes (a humanlike pattern) respond to low
      calcium diets with accelerated weight gain and fat accretion, whereas high
      calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase
      thermogenesis and suppress fat accretion and weight gain in animals maintained at
      identical caloric intakes. Further, low calcium diets impede body fat loss,
      whereas high calcium diets markedly accelerate fat loss in transgenic mice
      subjected to caloric restriction. Notably, dairy sources of calcium exert
      markedly greater effects in attenuating weight and fat gain and accelerating fat
      loss. This augmented effect of dairy vs. supplemental calcium is likely
      attributable to additional bioactive compounds in dairy that act synergistically
      with calcium to attenuate adiposity; among these are angiotensin converting
      enzyme inhibitory peptides, which limit angiotensin II production and thereby
      limit angiotensin II stimulation of adipocyte lipogenesis. These concepts are
      confirmed by both epidemiological and clinical data, which similarly demonstrate
      that dairy products exert a substantially greater effect on both fat loss and fat
      distribution compared to an equivalent amount of supplemental calcium.

PMID- 12514304
TI  - The conjugated linoleic acid (CLA) isomer, t10c12-CLA, is inversely associated
      with changes in body weight and serum leptin in subjects with type 2 diabetes
      mellitus.
AB  - Isomers of conjugated linoleic acid (CLA) are found in beef, lamb and dairy
      products. Diets containing CLA reduce adipose mass in various depots of
      experimental animals. In addition, CLA delays the onset of diabetes in the ZDF
      rat model for obesity-linked type 2 diabetes mellitus. We hypothesize that there
      would be an inverse association of CLA with body weight and serum leptin in
      subjects with type 2 diabetes mellitus. In this double-blind study, subjects with
      type 2 diabetes mellitus were randomized into one of two groups receiving either
      a supplement containing mixed CLA isomers (CLA-mix; 8.0 g daily, 76% pure CLA; n
      = 12) or a supplement containing safflower oil (placebo; 8.0 g daily safflower
      oil, n = 9) for 8 wk. The isomers of CLA in the CLA-mix supplement were primarily
      c9t11-CLA ( approximately 37%) and t10c12-CLA ( approximately 39%) in free fatty
      acid form. Plasma levels of CLA were inversely associated with body weight (P <
      0.05) and serum leptin levels (P < 0.05). When levels of plasma t10c12-CLA isomer
      were correlated with changes in body weight or serum leptin, t10c12-CLA, but not
      c9t11-CLA, was inversely associated with body weights (P < 0.05) and serum leptin
      (P < 0.02). These findings strongly suggest that the t10c12-CLA isomer may be the
      bioactive isomer of CLA to influence the body weight changes observed in subjects
      with type 2 diabetes. Future studies are needed to determine a causal
      relationship, if any, of t10c12-CLA or c9t11-CLA to modulate body weight and
      composition in subjects with type 2 diabetes. Furthermore, determining the
      ability of CLA isomers to influence glucose and lipid metabolism as well as
      markers of insulin sensitivity is imperative to understanding the role of CLA to
      aid in the management of type 2 diabetes and other related conditions of insulin
      resistance.

PMID- 12514305
TI  - The role of leucine in weight loss diets and glucose homeostasis.
AB  - Debate about the optimum balance of macronutrients for adult weight maintenance
      or weight loss continues to expand. Often this debate centers on the relative
      merits or risks of carbohydrates vs. fats; however, there is increasing interest
      in the optimal level of dietary protein for weight loss. Diets with a reduced
      ratio of carbohydrates/protein are reported to be beneficial for weight loss,
      although diet studies appear to lack a fundamental hypothesis to support higher
      protein intakes. Presently, needs for dietary proteins are established by the
      recommended daily allowance (RDA) as the minimum level of protein necessary to
      maintain nitrogen balance. The RDA define the primary use of amino acids as
      substrates for synthesis of body proteins. There is emerging evidence that
      additional metabolic roles for some amino acids require plasma and intracellular
      levels above minimum needs for protein synthesis. The branched-chain amino acid
      leucine is an example of an amino acid with numerous metabolic roles that
      function in proportion with cellular concentration. This review provides an
      overview of the current understanding of metabolic roles of leucine and proposes
      a metabolic framework to evaluate the merits of a higher protein diet for weight
      loss.

PMID- 12514306
TI  - Normalizing calcium intake: projected population effects for body weight.
AB  - Published data describing the inverse relationship between calcium intake and
      body weight in 564 women were evaluated for their dispersion around their means,
      and the fraction above any given weight or rate of weight gain was calculated
      from the parameters of the normal distribution for the variable concerned. At the
      25th percentile of calcium intakes, 15% of young women were overweight, and that
      fraction fell to only 4% at calcium intakes in the range of currently recommended
      values. Similarly, obesity prevalence in this cohort fell from 1.4 to 0.2% across
      the same difference in calcium intakes. At midlife, women at the 25th percentile
      of intakes gained weight, on average, at a rate of 0.42 kg/y. This gain dropped
      to -0.011 kg/y at currently recommended calcium intakes. Although calcium intake
      explains only a small fraction of the variability in weight or weight gain,
      shifting the mean of the distributions downward by increasing calcium intake can
      be estimated to reduce the prevalence of overweight and obesity by perhaps as
      much as 60-80%.

PMID- 12514307
TI  - Advances in retinoid research: mechanisms of cancer chemoprevention symposium
      introduction.

PMID- 12514308
TI  - Retinoid target gene activation during induced tumor cell differentiation: human
      embryonal carcinoma as a model.
AB  - Many agents that exhibit chemopreventive activity are able to mediate a
      differentiation response in premalignant and malignant tissues. One of the most
      widely studied classes of tumor differentiation agents is the retinoids. There is
      rapidly evolving evidence for beneficial retinoid actions in the prevention or
      treatment of clinical tumors. However, the use of retinoids in the clinic is
      limited by acquired resistance and toxicity, especially when administered
      chronically in preventive strategies. Although retinoids are known to regulate
      gene transcription by activating retinoid receptors, the identity of the target
      genes that mediate the beneficial effects of retinoids are largely unknown. Here
      we review a useful model of retinoid-induced tumor cell differentiation: human
      embryonal carcinoma. The pluripotent nature and ease of use make human embryonal
      carcinoma cells a valuable and practical complement to human embryonic stem cells
      as an in vitro model of early human development. In addition, retinoid treatment
      of human embryonal carcinoma is an important model of induced tumor cell
      differentiation because retinoids cause the reversal of the malignant phenotype
      coincident with terminal neuronal differentiation. We have used both de novo and
      candidate approaches with this system in an effort to uncover critical downstream
      targets of retinoid receptors during differentiation induction.

PMID- 12514309
TI  - Pharmacological doses of some synthetic retinoids can modulate both the aryl
      hydrocarbon receptor and retinoid receptor pathways.
AB  - Retinoids have been demonstrated to have pharmacological application in the areas
      of dermatology and oncology. In addition to the natural retinoids such as all
      trans-retinoic acid and 9-cis-retinoic acid, many new potential retinoid drugs
      have been synthesized, including retinoic acid receptor (RAR)-subtype selective
      agonists, retinoid X receptor (RXR)-selective agonists, RAR-selective
      antagonists, anti-AP1-specific retinoids and retinoids that induce apoptosis.
      Recent studies demonstrate that some retinoids, in addition to modulating the
      RAR/RXR pathway, are also capable at pharmacological concentrations of binding to
      aryl hydrocarbon receptor (AhR) and activating the AhR/AhR nuclear translocator
      pathway. Future studies are necessary to ascertain the consequences, if any, of
      activation of the AhR signaling pathway by pharmacological doses of specific
      retinoids.

PMID- 12514310
TI  - Vitamin A (retinoids) regulation of mouse melanoma growth and differentiation.
AB  - The incidence of melanoma is rapidly increasing in the U.S. population. At the
      present, there is no effective chemotherapy against invasive melanoma. At our
      laboratory, we have been studying retinoic acid (RA)-induced growth arrest and
      differentiation in the B16 murine melanoma cell model. Several immediate-early
      gene targets of RA were identified by gene arrays. In one of these genes, T-box
      binding protein-2 (Tbx-2), an RA response element, was identified in the promoter
      region that mediates the RA responsiveness of this gene. RA also induces a
      sixfold to eightfold increase in protein kinase C (PKC)alpha RNA and protein.
      This gene is not a direct target of RA but appears to be required for the
      biological effects of RA in B16 melanoma cells. PKC can alter gene transcription
      via phosphorylation of activator protein (AP)-1. RA increased AP-1 activity in
      B16 cells but with delayed kinetics compared with activation of PKC by phorbol
      dibutyrate. Clones stably expressing a dominant negative A-fos gene had reduced
      AP-1 activity and were less sensitive to RA induction of growth arrest and
      differentiation. Paradoxically, although inhibition of PKC enzyme activity
      blocked phorbol dibutyrate-stimulated AP-1 activity, it had no effect on RA
      induced AP-1 activity. Further investigation showed that PKC enzyme activity was
      not required for RA-induced growth inhibition or stimulation of melanin
      synthesis. These data suggest that PKCalpha either works through a nonenzymatic
      protein-protein mechanism or may interfere with the enzymatic function of another
      isozyme of PKC to mediate the actions of RA in B16 melanoma cells.

PMID- 12514311
TI  - Retinoids and alcohol-related carcinogenesis.
AB  - Chronic and excessive alcohol intake is associated with an increased incidence of
      a variety of cancers (e.g., liver, oral cavity, esophagus, colorectal and
      breast). Long-term alcohol intake results in impaired nutritional status of
      retinoic acid (RA), the most active derivative of vitamin A, which may provide a
      promoting environment for tumor formation. Recent studies demonstrate that
      chronic alcohol-induced hepatocellular proliferation, which may convert
      hepatocytes from a state of resistance to a carcinogen to a state of high
      susceptibility, is due to alcohol-impaired RA metabolism and signaling and
      crosstalk with the Jun N-terminal kinases-dependent signaling pathway. Further,
      the restoration of hepatic RA homeostasis by treatment with either RA
      supplementation or inhibitors of RA catabolism can suppress alcohol-induced
      hepatocyte hyperproliferation and restore alcohol-deregulated apoptosis, thereby
      reducing the risk of alcohol-promoted hepatocellular carcinogenesis. These
      studies indicate the importance of RA actions in the prevention and/or treatment
      of alcohol-related carcinogenic process in the liver and other organs.

PMID- 12514312
TI  - Retinoid production and catabolism: role of diet in regulating retinol
      esterification and retinoic Acid oxidation.
AB  - Retinoic acid (RA), a transcriptionally active metabolite of vitamin A (retinol),
      activates two families of nuclear retinoid receptors that have the potential to
      regulate the expression of a large number of genes. Although it may be presumed
      that the concentration of RA is closely regulated, the mechanisms underlying such
      regulation are not well understood. Our research has examined the expression and
      function of two enzymes, lecithin:retinol acyltransferase (LRAT) and a cytochrome
      P450, CYP26, in the liver and lung of rats and mice, over a wide range of vitamin
      A status or after treatment of vitamin A-deficient animals with exogenous RA.
      LRAT expression at both the mRNA and protein activity levels and CYP26 mRNA are
      regulated by dietary vitamin A in a steady-state model and are acutely regulated
      by RA in an acute repletion model. In the liver, the level of expression of LRAT
      and CYP26 is as follows: vitamin A deficient < vitamin A marginal < vitamin A
      adequate < vitamin A supplemented < RA treated. The regulation of LRAT shows
      strong tissue specificity (highly regulated in liver and lung but not in small
      intestine), whereas CYP26 is strongly regulated in the liver, lung, testis and
      intestine. RA may function as a signal of the body's vitamin A adequacy. The
      regulated expression of LRAT, CYP26 and other genes by RA may provide a sensitive
      response mechanism that overall serves to adjust the metabolism of vitamin A to
      maintain retinoid homeostasis and prevent retinoid excess.

PMID- 12514313
TI  - Interrelationships between power-related and belief-related factors determine
      nutrition in populations.
AB  - The vast majority of social research in nutrition has focused either on economic,
      material and political factors ("power-related" variables) or on psychological,
      cultural and attitudinal factors ("belief-related" variables). Even when data on
      both classes of factors are collected, the orientation in analysis is to treat
      one of the two classes as "confounding" or "control" variables. Although single
      focus studies have yielded essential knowledge about the role of specific
      factors, they fail to reveal the mechanisms through which belief-related and
      power-related variables interact to produce nutritional outcomes. Data from the
      Nutrition CRSP project in Mexico are used to illustrate the interactions between
      household economic conditions and maternal education on household diet. As has
      been seen in other developing country contexts, women in more favorable economic
      circumstances, and who have more education, tend to feed their children a higher
      quality diet. However, even in better-off households dietary quality is not
      uniformly high, a finding that reflects the operation of other values and
      cultural factors that direct resource allocation to other sectors of family
      activity.

PMID- 12514314
TI  - Participation, power and beliefs shape local food and nutrition policy.
AB  - Community participation is believed to hold a number of benefits, including the
      incorporation of local knowledge in planning, generation of greater support for
      and sustainability of local actions and being consistent with democratic values.
      These claimed benefits were examined in upstate New York, where 3-d participatory
      planning events were convened in each of six communities, focusing on desired
      changes in the local food system. A variety of qualitative and quantitative
      methods were used to assess the following: 1) local values, interests and beliefs
      (viewpoints) related to food and the food system before and after the planning
      events; 2) fairness and effectiveness in agenda setting; and 3) implementation of
      actions during the 2 y following the events. Despite marked variation in
      viewpoints, participants readily agreed on desired changes in the local food
      system during the events and they considered the process to be a fair and
      positive experience. However, the action agendas, follow-up actions and changes
      in viewpoints after the events displayed systematic tendencies to deviate from
      revealed common interests or interests of disenfranchised participants. This
      reflected differences in the fairness and effectiveness of participation during
      and after the events, established agendas and preferences of local institutions
      and a variety of market and regulatory barriers.

PMID- 12514315
TI  - Breastfeeding among low income, African-American women: power, beliefs and
      decision making.
AB  - Breastfeeding rates among African-American women lag behind all other ethnic
      groups. National data show that only 45% of African-American women reported ever
      breastfeeding compared to 66 and 68% of Hispanic and white women, respectively.
      Of African-American women who do choose to breastfeed, duration is short, with
      many discontinuing in the first days after birth. This report applies a social
      ecological framework to breastfeeding to investigate macrolevel-microlevel
      linkages. We posit that macrolevel factors, such as the media, aggressive
      marketing of breastmilk substitutes, welfare reform, hospital policy and
      breastfeeding legislation, interact with microlevel factors to influence a
      woman's decision to breastfeed. These microlevel factors include features of the
      community, neighborhoods, workplaces that support or discourage breastfeeding,
      social and personal networks and cultural norms and individual beliefs about
      breastfeeding. The report discusses how power operates at each level to influence
      women's choices and also emphasizes the value of ethnographic data in
      breastfeeding studies. Through a case study of a sample of low income, African
      American women living in Baltimore, MD, where breastfeeding role models are few,
      beliefs that discourage breastfeeding are many, and where everyday life is full
      of danger and fear, it is understandable that breastfeeding is not considered
      practical. The narrative data provide important information that can be used to
      enhance intervention efforts. To reach the Surgeon General's Healthy People 2010
      breastfeeding goals requires a shift in cultural norms and structures at all
      levels that will support breastfeeding for all women.

PMID- 12514316
TI  - Macro- and microlevel processes affect food choice and nutritional status in the
      republic of the marshall islands.
AB  - Despite its relative isolation from the world stage and lack of resources, the
      Marshall Islands serve as an example of the interaction between global political
      power, macroeconomic forces and local cultural factors. At the national level,
      patterns of food importation and government programs encourage the consumption of
      high fat foods. These factors have fostered dependency on Western foods and a
      loss of traditional food practices. Beliefs come into play as microlevel factors
      that influence food choice and aspects of lifestyle. Nearly three quarters of
      women are overweight or obese in this setting. Obesity in women is associated
      with greater age, higher education and more imported food consumption. Over a
      third of children ages 1-5 y are stunted, with stunting associated with worse
      economic status, less active feeding, increased consumption of imported foods and
      urban residence. What can be done at the microlevel is constrained by macrolevel
      factors of disempowerment. In this way, issues of power and belief are played out
      in the bodies of individuals.

PMID- 12514317
TI  - Symposium introduction.

PMID- 12514318
TI  - Historical concepts of interactions, synergism and antagonism between nutrition
      and infection.
AB  - In the 1950s textbooks of nutrition made little or no mention of a relation to
      infection. The same was true for treatises on infectious disease. Relevant
      studies in experimental animals and a number of classical clinical observations
      were available pointing out the role of infection in precipitating nutritional
      disorders. However, clinicians and nutritionists did not recognize the importance
      of the relationship. The field and metabolic studies of the Institute of
      Nutrition of Central America and Panama (INCAP) in the 1950s demonstrated that
      malnutrition and infection in humans are generally synergistic. These studies
      stimulated the review of available evidence that resulted in the 1968 WHO
      monograph on "Interactions of Nutrition and Infection." It provided extensive
      evidence for the role of infections in precipitating clinical malnutrition and
      for the impact of malnutrition on morbidity and mortality from infection. The
      high frequency of diarrhea in underprivileged young children led to intensive
      studies in many countries of its effect on nutritional status and to recognition
      of the high prevalence of "weanling diarrhea." The effects of infection on
      nutritional status were then extensively and elegantly investigated at Fort
      Detrick, MD, and hormonal and cytokine mechanisms identified. The subsequent
      explosion in knowledge of cell-mediated immune mechanisms has led to an
      understanding of how malnutrition lowers this resistance. Today, recognition of
      the synergistic relationship between nutrition and infection influences most
      public health interventions to prevent malnutrition.

PMID- 12514319
TI  - Metabolic effects of infection on protein and energy status.
AB  - A review of some of the seminal studies of metabolism during various infections
      indicates that similar patterns of metabolic alterations occur during these
      illnesses. This patterned metabolic array occurs whether the infection is caused
      by a gram-positive or a gram-negative bacterium, a rickettsia or a virus, or is
      respiratory or systemic. In all instances, the previously healthy host responds
      to infection with cytokine-mediated alterations that appear to occur in
      proportion to the infectious challenge and to the likelihood of death. These
      alterations also can occur in the vaccinated host, if the infectious challenge is
      sufficiently great. Because of their widespread occurrence and seemingly
      ingrained status, these metabolic alterations may be presumed to be of survival
      benefit to the host. Whether this patterned array of metabolic sequelae is of
      benefit to the host, or even to the species, its widespread and systematic
      occurrence allows it to be of value in assessing the safety and efficacy of
      vaccines and drugs to prevent or treat a wide variety of infections. In this era
      of bioterrorism, wherein drugs and vaccines may have to be approved for human use
      without clinical trials and solely on the basis of animal data, these cytokine
      mediated metabolic sequelae can aid in the rational selection of drug and vaccine
      candidates.

PMID- 12514320
TI  - Diarrhea and malnutrition.
AB  - Publication of the WHO monograph, "Interactions of Nutrition and Infection," in
      1968 by Scrimshaw, Taylor and Gordon stimulated many scientists to pursue further
      research on these issues. With regard to the relationships between diarrhea and
      malnutrition, the research conducted since 1968 can be categorized in one of
      three major areas: 1) the impact of diarrhea on nutritional status, particularly
      in young children; 2) nutritional risk factors for diarrhea; and 3) appropriate
      dietary therapy for patients during and after enteric infections. The results of
      these studies have prompted a number of changes in the clinical treatment of
      patients with diarrhea and in public health policies regarding its prevention.

PMID- 12514321
TI  - Tropical enteritis: nutritional consequences and connections with the riddle of
      cholera.
AB  - One of the important consequences of the infection-nutrition interaction is
      mediated by malabsorption associated with chronic inflammation in the intestine,
      enteritis. Studies made possible after development of the peroral intestinal
      biopsy technique in the 1950s indicated the wide prevalence of enteropathy,
      particularly in tropical developing countries with poor levels of sanitation.
      Some consider this so-called subclinical tropical malabsorption to be the base of
      an iceberg, whose tip is tropical sprue, a severe form of malabsorption leading
      to nutritional deficiency that had been reported in colonial expatriates in
      tropical countries for 200 y. Some of the first demonstrations of the prevalence
      of tropical enteritis in Asia were made in quest of the pathologic lesion of
      cholera, and further examination of the water and electrolyte, as well as
      nutrient, malabsorption in cholera led serendipitously to the discovery of the
      oral rehydration solution for the treatment of diarrheal disease.

PMID- 12514322
TI  - The history of nutrition: malnutrition, infection and immunity.
AB  - The relationship between nutritional status and the immune system has been a
      topic of study for much of the 20th century. Dramatic increases in our
      understanding of the organization of the immune system and the factors that
      regulate immune function have demonstrated a remarkable and close concordance
      between host nutritional status and immunity. This report traces the increasing
      sophistication of our understanding of these relationships and their impact on
      susceptibility to infection through six stages to the present time. The cyclical
      relationship between poor nutrition, increased susceptibility to infectious
      diseases, leading to immunological dysfunction and metabolic responses that
      further alter nutritional status is described and, wherever possible, related to
      physiological mechanisms. In addition, the particular role of Nevin Scrimshaw in
      guiding the progress over the past 50 y is discussed.

PMID- 12514323
TI  - Artificial cells: unique insights into exocytosis using liposomes and lipid
      nanotubes.
AB  - Exocytosis is the fundamental process underlying neuronal communication. This
      process involves fusion of a small neurotransmitter-containing vesicle with the
      plasma membrane of a cell to release minute amounts of transmitter molecules.
      Exocytosis is thought to go through an intermediate step involving formation of a
      small lipid nanotube or fusion pore, followed by expansion of the pore to the
      final stage of exocytosis. The process of exocytosis has been studied by various
      methods; however, when living cells are used it is difficult to discriminate
      between the molecular effects of membrane proteins relative to the mechanics of
      lipid-membrane-driven processes and to manipulate system parameters (e.g.,
      membrane composition, pH, ion concentration, temperature, etc.). We describe the
      use of liposome-lipid nanotube networks to create an artificial cell model that
      undergoes the later stages of exocytosis. This model shows that membrane
      mechanics, without protein intervention, can drive expansion of the fusion pore
      to the final stage of exocytosis and can affect the rate of transmitter release
      through the fusion pore.

PMID- 12514324
TI  - Biological rhythm in livestock.
AB  - The animal time structure is a basic fact of life, no matter if one wants to
      study it or not. The time-dependent, mostly rhythmic, and thus to a certain
      degree predictable, variations of biochemical and physiological functions and of
      sensitivity and resistance to many environmental agents are often quite large and
      offer not only new insight into animal physiology and pathology but also
      diagnostic possibilities and therapeutic advantages. Chronobiology,
      chronophysiology and its subspecialities, like chronopharmacology and
      chronotherapy, will certainly play an important role in the clinical medicine of
      the future. Successful application of chronobiology to veterinary clinical
      medicine, however, depends critically on a thorough knowledge of its basic
      principles.

PMID- 12514325
TI  - Seroprevalence of antibody to procine reproductive and respiratory syndrome virus
      in diagnostic submissions.
AB  - During the period from January to December of 2001, a total of 3,391 swine sera
      were submitted to our laboratory from 256 farms for the diagnosis of porcine
      reproductive and respiratory syndrome (PRRS). The antibody to porcine
      reproductive and respiratory syndrome virus (PRRSV) was tested by the indirect
      immunofluorescent antibody (IFA) test. Of the 256 farms tested, 230 farms (89.8%)
      were positive for the PRRSV antibody. The overall seroprevalence of the PRRSV
      antibody was 52.1% (1765/3391). Most of the pigs seemed to be infected with PRRSV
      at around 50 to 60 days old. The seroprevalence of the antibody became higher
      with age, and peaked at around 100 days old. More than one-third of the adult
      pigs, including boars, gilts, and sows, was positive for the PRRSV antibody. The
      infection of PRRSV was chronic and confined to growers and/or finishers in most
      farms. However, the antibody was detected in all production phases at some farms.

PMID- 12514326
TI  - Mycobacterium bovis infection in a farmed elk in Korea.
AB  - A case of tuberculosis is reported in an eight-year-old, male, elk (Cervus
      elaphus nelsoni). The elk showed severe coughing, respiratory distress, abdominal
      breathing, anorexia, and severe progressive emaciation in the elk farm. At
      necropsy, the elk appeared in poor body condition. Mild enlargement of
      retropharyngeal and submandibular lymph node was observed in the head. Diffuse
      fibrinous pleuritis and purple red lobar pneumonia were found in the thorax. Well
      demarcated numerous dark yellow discrete or confluent nodules from 0.3 to 2 cm in
      diameter were scattered in the whole lung. Bronchial and mediastinal lymph nodes
      were also enlarged. Histopathologically, lungs had typical classical tuberculous
      granulomas, multiple abscesses, and numerous macrophages and Langhans giant cells
      infiltration in alveolar lumen. In the lymph nodes, there were small clusters of
      necrosis and infiltration of numerous macrophages, epithelioid cells, and
      Langhans giant cells. With the acid-fast staining, numerous mycobacteria were
      revealed in the lung and lymph nodes. According to this study, there are
      differences of the histopathologic lesions and the numbers of acid-fast bacilli
      in the lesions between this elk and cattle. Mycobacterium bovis was confirmed as
      a causative agent in this elk using bacterial isolation, biochemical
      characteristics, and PCR technique. The isolate was negative for niacin test,
      nitrate reductase, and pyrazinamidase. This is a first report for bovine
      tuberculosis of farmed elk in Asia.

PMID- 12514327
TI  - Immunohistochemical study of the pancreatic endocrine cells in the BALB/c mice:
      an unique distributional pattern of glucagon.
AB  - The regional distribution and relative frequency of insulin-, glucagon-,
      somatostatin- and pancreatic polypeptide (PP)-producing endocrine cells in the
      pancreas of BALB/c mouse were investigated by immunohistochemical method. The
      pancreas of mice was divided into two portions; pancreatic islets and exocrine
      portions, and pancreatic islets were further subdivided into two regions (central
      and peripheral regions) and the relative frequency and regional distribution of
      immunoreactive cells against insulin, glucagon, somatostatin and PP antisera were
      monitored. In the pancreatic islet portions, insulin-immunoreactive cells were
      located in the central regions and they were randomly dispersed in the whole
      pancreatic islets in some case of the small islets. Quite different from those of
      other mammals, glucagon-immunoreactive cells were dispersed throughout central to
      peripheral regions in case of large islets and in the smaller ones, most of these
      cells were situated in the peripheral regions. Somatostatin-immunoreactive cells
      were detected in the peripheral regions with various frequencies. Although some
      cells were demonstrated in the central regions of pancreatic islets, most of PP
      immunoreactive cells were located in the peripheral regions. In the exocrine
      portions, all four types of immunoreactive cells were demonstrated in the BALB/c
      mouse. Some peculiar distributional patterns of pancreatic endocrine cells were
      found in BALB/c mouse, especially in case of glucagon-immunoreactive cells.

PMID- 12514328
TI  - Immunohistochemistry of voltage-gated calcium channel alpha1B subunit in mouse
      cerebellum.
AB  - Secretion of neurotransmitters is initiated by voltage-gated calcium influx
      through presynaptic, voltage- gated N-type calcium channels. However, little is
      known about their cellular distribution in the mouse cerebellum. In the
      cerebellum, alpha1B immunoreactivity is found mainly on the cell bodies of all
      Purkinje cells. In addition, the immunoreactivity was detected on a subset of
      Purkinje cell dendrites, clustered to form a parasagittal array of bands. In the
      anterior lobe vermis, immunoreactive Purkinje cell dendrites form narrow stripes
      separated by broad bands of unstained dendrites. Moving caudally through the
      vermis, these stripes become thicker as a larger fraction of the Purkinje cell
      dendrites become immunoreactive. This localization study of the alpha1B pore
      forming subunits in mouse cerebellum may guide future investigations of the role
      of calcium channels in neurological pathways.

PMID- 12514329
TI  - SR144528 as inverse agonist of CB2 cannabinoid receptor.
AB  - It is now well established that several G protein- coupled receptors can signal
      without agonist stimulation (constitutive receptors). Inverse agonists have been
      shown to inhibit the activity of such constitutive G protein-coupled receptor
      signaling. Agonist activation of the G(i/o)-coupled peripheral cannabinoid
      receptor CB2 normally inhibits adenylyl cyclase type V and stimulates adenylyl
      cyclase type II. Using transfected COS cells, we show here that application of
      SR144528, an inverse agonist of CB2, leads to a reverse action (stimulation of
      adenylyl cyclase V and inhibition of adenylyl cyclase II). This inverse agonism
      of SR144528 is dependent on the temperature, as well as on the concentration of
      the cDNA of CB2 transfected. Pertussis toxin blocked the regulation of adenylyl
      cyclase activity by SR 144528.

PMID- 12514330
TI  - Functional role of serine residues of transmembrane dopamin VII in signal
      transduction of CB2 cannabinoid receptor.
AB  - Using site-directed mutagenesis technique, I have replaced serine 285 and serine
      292 with the alanine, and assessed the binding of agonist and signaling such as
      the inhibition of adenylyl cyclase activity. I have found that serine 292 has an
      important role in the signal transduction of cannabinoid agonists, HU-210 and
      CP55940, but not in that of aminoalkylindoles derivatives WIN55,212-2. All
      mutants express well in protein level determined by western blot using monoclonal
      antibody HA 11 as compared with the wild type receptor. Interestingly, binding
      affinity of S285A and S292A mutants with classical cannabinoid agonist HU-243 was
      somewhat decreased. In signaling assay, the inhibition of adenylyl cyclase by HU
      210, CP55940 and WIN55,212-2 is the same order in both wild type receptor and
      S285A mutant receptor. However, S292A have been shown that the inhibition curves
      of adenylyl cyclase activity moved to the right by HU-210 and CP55940, but those
      of adenylyl cyclase activity did not by aminoalkylindole WIN55,212-2, which is
      indicating that this residue is closely related to the binding site with HU-210
      and CP55940. In addition, serine 292 might take more important role in CB2
      receptor and G-protein signaling than serine 285.

PMID- 12514331
TI  - Effects of electroacupuncture on minimum alveolar concentration of isoflurane and
      cardiovascular system in isoflurane anesthetized dogs.
AB  - The effects of electroacupuncture (EA) on the minimum alveolar concentration
      (MAC) and on the cardiovascular system were evaluated with dogs under isoflurane
      anesthesia. Eight healthy male beagles were randomly assigned to six study groups
      (five heads/group) with washout intervals of 7 ~ 31 days between experiments for
      recovery and anesthetic clearance. MAC of isoflurane and cardiovascular
      parameters were determined after EA at nonacupoint and and at acupoints LI-4, SP
      6, ST-36 and TH-8. Electroacupuncture for 30 minutes at LI-4, SP-6, ST-36 and TH
      8 acupoints lowered the MAC of isoflurane by 17.5 +/- 3.1%, 21.3 +/- 8.0%, 20.5
      +/- 8.2% and 15.6    3.1%, respectively (p < 0.05). However, electrical
      stimulation of nonacupoint did not induce a significant change in MAC of
      isoflurane. In the cardiovascular system, the ST-36 group did not induce any
      significant change in cardiovascular parameters. In the TH-8 group, the mean and
      diastolic arterial pressure and the systemic vascular resistance were decreased.
      In the LI-4 group, cardiac output and cardiac index decreased after EA. These
      results indicate that EA at LI-4, SP-6 and ST-36 have advantages in isoflurane
      anesthesia in terms of reducing the dose of anesthetics and minimizing
      cardiovascular side effects.

PMID- 12514332
TI  - Influence of isoflurane anesthesia on pulsatility index and peak systolic
      velocity of basilar artery in dogs by Doppler ultrasonography.
AB  - This study was performed to examine the influence of isoflurane anesthesia on the
      pulsatility index (PI) and the peak systolic velocity (PSV) of the blood flow in
      the basilar artery of dogs by duplex Doppler ultrasonography. Twelve healthy dogs
      were used to measure the PI and the PSV under the conscious state and isoflurane
      anesthesia. The pulsatility index (PI) and the peak systolic velocity (PSV) in
      the basilar artery were measured five times with random intervals. The blood
      pressure was measured. The PI and PSV values in dogs under isoflurane anesthesia
      were 1.37 +/- 0.32 and 72 +/- 19 cm/sec, whereas those in the conscious dogs were
      1.37 +/- 0.13 and 81 +/- 16 cm/sec, respectively. The indirect mean arterial
      systolic and diastolic pressures under isoflurane anesthesia were 107 and 51
      mmHg, whereas those in the conscious dogs were 133 and 74 mmHg. Though the
      isoflurane is generally known to induce hypotension, there were no significant
      differences in the PI and PSV between the isoflurane-anesthetized and the
      conscious dogs. In conclusion, the isoflurane anesthesia did not influence the PI
      and PSV in the basilar artery of dogs.

PMID- 12514333
TI  - Expression of recombinant porcine interleukin-2 and application of its antibody
      to immunoassays.
AB  - Interleukin-2 plays an important role in T lymphocyte proliferation and immune
      response regulations. In this study, porcine IL-2 cDNA was cloned from peripheral
      blood mononuclear cells, and recombinant porcine IL-2 (rpIL-2) was expressed in
      Escherichia coli. The size of rpIL-2 without signal peptides was about 15 kDa
      when determined by SDS-PAGE and Western blotting analysis. Anti-rpIL-2 antibody
      was produced from mice immunized with the purified rpIL-2, and its specificity
      was examined by Western blotting and ELISA. In the Western blotting assay, anti
      rpIL-2 and anti-recombinant human IL-2 (rhIL-2) antibodies specifically
      recognized rpIL-2 and rhIL-2, respectively. However, anti-rpIL-2 antibody did not
      recognize rhIL-2, and anti-rhIL-2 antibody also did not react with rpIL-2 in the
      same assay. In ELISA, anti-rpIL-2 antibody strongly interacted with both rpIL-2
      and rhIL-2, and anti-rhIL-2 antibody also efficiently recognized both proteins.
      Taken together, the specificity of anti-rpIL-2 antibody for rpIL-2 was
      demonstrated by Western blotting and ELISA. It was also shown that ELISA is more
      efficient than Western blotting in determining the species cross-reactivity of
      anti-rpIL-2 antibody.

PMID- 12514334
TI  - Frequencies of micronuclei in peripheral lymphocytes in Korean populations after
      chronic low-dose radiation exposure.
AB  - The purpose of this study was to estimate predictive markers of intrinsic
      radiosensitivity in individuals who were exposed to occupational or environmental
      radiation. Throughout this process, the actual biohazard risks and base-line
      chromosome damage were evaluated in human population. Further studies were
      carried out to provide evidence for the existence of individual variations in age
      dependent responses through micronuclei (MN) assay. Spontaneous frequencies not
      only vary greatly between individuals, but also working or living areas. It was
      shown that the increased level of spontaneous cell with MN was observed with
      increasing age. The relationship between radiosensitivity and the increased
      spontaneous level of MN may be in an inverse proportion. Ionizing radiation may
      be targeted mutagenic effects at the usual exposures of background levels that
      populations were exposed. Age and gender are the most important demographic
      variables in determining the MN index with frequencies in females, which were
      greater than those in males. The main life-style factors influencing the MN index
      in subjects were correlated significantly and positively with smoke. The results
      showed that an indicator of the genetic damaged rate in MN index in human
      populations significantly correlated with age, sex and life-style factors. So
      far, it is evident that with regard to the application of MN assay all future
      studies have to take into account the influence of age, gender, and life-style.
      In Conclusion, using micronuclei assay technique a large population can be easily
      monitored. This study illustrated that the MN assay may provide a high potential
      to ensure appropriate quality control and standard documentation protocol that
      can be used to monitor a large population exposed to radiation epidemiologically.

PMID- 12514335
TI  - Development and evaluation of a new apparatus for continuous perfusion of
      isolated perfused pig heart.
AB  - To develop a better model of isolated perfused heart, a new apparatus of coronary
      artery cannula- fixed-in-aortic tube was developed for continuous normothermic
      perfusion and compared to the Casalis apparatus with cold ischemia. Eight mongrel
      pigs with the body weight of 18 to 24 kg were divided half into two groups. All
      the continuous perfusion experimental hearts resumed a spontaneous heart beat and
      stabilized earlier than the control hearts without the need of defibrillator or
      pacemaker, indicating no reperfusion injury on the heart. All the experimental
      hearts did not show fibrillation nor stopped beating during the entire
      experiment, whereas the control hearts fibrillated. Two control hearts stopped
      beating, and only one of the two survived with the help of pacemaker.The coronary
      systolic, diastolic, and mean pressures were more stable with low variation in
      the experimental hearts than the cold ischemic control hearts. The experimental
      hearts consumed more oxygen than the control hearts, indicating more cardiac
      output. According to these results, the continuous normothermic perfusion method
      by the new cannula, even though with a short-period of hypothermic perfusion,
      provided better myocardial protection than the cold ischemia.

PMID- 12514336
TI  - Regional distribution and relative frequency of gastrointestinal endocrine cells
      in large intestines of C57BL/6 mice.
AB  - The regional distributions and relative frequencies of some gastrointestinal
      endocrine cells in the three portions (cecum, colon and rectum) of the large
      intestinal tract of C57BL/6 mice were examined with immunohistochemical method
      using 7 types of specific antisera against chromogranin A (CGA), serotonin,
      somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and
      cholecyctokinin (CCK)-8. In this study, all 3 types of immunoreactive (IR) cells
      were identified. Most of these IR cells in the large intestinal portion were
      generally spherical or spindle in shape (open-typed cell) while cells with a
      round shape (close-typed cell) were found in the intestinal gland. Their relative
      frequencies varied according to each portion of the large intestinal tract. CGA
      IR cells were found throughout the whole large intestinal tract but were most
      predominant in the colon. Serotonin-IR cells were detected throughout the whole
      large intestinal tract and showed highest frequency in the colon. Peculiarly,
      glucagon-IR cells were restricted to the colon with a low frequency. However, no
      somatostatin-, HPP-, gastrin- and CCK-8-IR cells were found in the large
      intestinal tract. In conclusion, some peculiar distributional patterns of large
      intestinal endocrine cells were identified in C57BL/6 mice.

PMID- 12514337
TI  - Immunohistochemical localization of nerve growth factor, glial fibrillary acidic
      protein and ciliary neurotrophic factor in mesencephalon, rhombencephalon, and
      spinal cord of developing mongolian gerbil.
AB  - The distribution of the nerve growth factor (NGF), the glial fibrillary acidic
      protein (GFAP) and the ciliary neurotrohic factor (CNTF) was performed in coronal
      sections of the mesencephalon, rhombencephalon and spinal cord in the developing
      Mongolian gerbils. Generally, NGF specifically recognizes neurons with the NGF
      receptor, whereas GFAP does the glia, and CNTF does the motor neurons. The
      receptor expression was examined separately in gerbils between embryonic days 15
      (E15) and postnatal weeks 3 (PNW 3). The NGF-IR was first observed in the spinal
      cord at E21, which might be related to the maturation. The GFAP reactivity was
      peaked at the postnatal days 2 (PND2), while the highest CNTF-reaction was
      expressed at PNW 2. The GFAP stains were observed in the aqueduct and the spinal
      cord, which appeared to project laterally at E19. The CNTF was observed only
      after the birth and found in both the neurons and neuroglia of the substantia
      nigra, mesencephalon, cerebellum and the spinal cord from PND1 to PNW3. These
      results suggest that NGF, GFAP and CNTF are important for the development of the
      neurons and the neuroglia in the central nervous system at the late prenatal and
      postnatal stages.

PMID- 12514338
TI  - Intracranial and spinal ependymomas: review of MR images in 61 patients.
AB  - OBJECTIVE: To compare the age distribution and characteristic MR imaging findings
      of ependymoma for each typical location within the neuraxis. MATERIALS AND
      METHODS: During a recent eleven-year period, MR images of 61 patients with
      histologically proven ependymomas were obtained and retrospectively reviewed in
      terms of incidence, peak age, location, size, signal intensity, the presence or
      absence of cyst and hemorrhage, enhancement pattern, and other associated
      findings. RESULTS: Among the 61 patients, tumor location was spinal in 35 (57%),
      infrartentorial in 19 (31%), and supratentorial in seven (12%). In four of these
      seven, the tumor was located in brain parenchyma, and in most cases developed
      between the third and fifth decade. Approximately half of the infratentorial
      tumors occurred during the first decade. The signal intensity of ependymomas was
      nonspecific, regardless of their location. A cystic component was seen in 71%
      (5/7) of supratentorial, 74% (14/19) of infratentorial, and 14% (5/35) of spinal
      cord tumors. Forty- nine percent (17/35) of those in the spinal cord were
      associated with rostral and/or caudal reactive cysts. Intratumoral hemorrhage
      occurred in 57% (4/7) of supratentorial, 32% (6/19) of infratentorial, and 9%
      (3/35) of spinal cord tumors. In 17% (6/35) of spinal ependymomas, a curvilinear
      low T2 signal, suggesting marginal hemorrhage, was seen at the upper and/or lower
      margins of the tumors. Peritumoral edema occurred in 57% (4/7) of supratentorial,
      6% (3/19) of infratentorial and 23% (8/35) of spinal cord tumors. Seventy-two
      percent (5/7) of supratentorial and 95% (18/19) of infratentorial tumors showed
      heterogeneous enhancement, while in 50% (17/34) of spinal cord tumors,
      enhancement was homogeneous. CONCLUSION: Even though the MR imaging findings of
      ependymomas vary and are nonspecific, awareness of these findings, and of tumor
      distribution according to age, is helpful and increases the likelihood of correct
      preoperative clinical diagnosis.

PMID- 12514339
TI  - Superficial endobronchial lung cancer: radiologic-pathologic correlation.
AB  - OBJECTIVE: To analyze the plain chest radiographic and CT findings of superficial
      endobronchial lung cancer and to correlate these with the findings of
      histopathology. MATERIALS AND METHODS: This study involved 19 consecutive
      patients with pathologically proven lung cancer confined to the bronchial wall.
      Chest radiographs and CT scans were reviewed for the presence of parenchymal
      abnormalities, endobronchial nodules, bronchial obstruction, and bronchial wall
      thickening and stenosis. The CT and histopathologic findings were compared.
      RESULTS: Sixteen of the 19 patients had abnormal chest radiographic findings,
      while in 15 (79%), CT revealed bronchial abnormalities: an endobronchial nodule
      in seven, bronchial obstruction in five, and bronchial wall thickening and
      stenosis in three. Histopathologically, the lesions appeared as endobronchial
      nodules in 11 patients, irregular thickening of the bronchial wall in six,
      elevated mucosa in one, and carcinoma in situ in one. CONCLUSION: CT helps detect
      superficial endobronchial lung cancer in 79% of these patients, though there is
      some disagreement between the CT findings and the pathologic pattern of bronchial
      lesions. Although nonspecific, findings of bronchial obstruction or bronchial
      wall thickening and stenosis should not be overlooked, and if clinically
      necessary, bronchoscopy should be performed.

PMID- 12514340
TI  - The significance of perfusion defect at myocardial perfusion MR imaging in a cat
      model of acute reperfused myocardial infarction.
AB  - OBJECTIVE: To determine whether the size of a perfusion defect seen at myocardial
      perfusion MR imaging represents the extent of irreversibly damaged myocardium in
      acute reperfused myocardial infarction. MATERIALS AND METHODS: In nine cats,
      reperfused myocardial infarction was induced by occlusion of the left anterior
      descending coronary artery for 90 minutes and subsequent reperfusion for 90
      minutes. At single-slice myocardial perfusion MR imaging at the midventricular
      level using a turbo-FLASH sequence, 60 short-axis images were sequentially
      obtained with every heart beat after bolus injection of gadomer-17. The size of
      the perfusion defect was measured and compared with both the corresponding
      unstained area seen at triphenyl tetrazolium chloride (TTC) staining and the
      hyperenhanced area seen at gadophrin-2- enhanced MR imaging performed in the same
      cat six hours after myocardial perfusion MR imaging. RESULTS: The sizes of
      perfusion defects seen at gadomer-17-enhanced perfusion MR imaging, unstained
      areas at TTC staining, and hyperenhanced areas at gadophrin-2-enhanced MR imaging
      were 20.4+/-4.3%, 29.0+/-9.7%, and 30.7+/- 10.6% of the left ventricular
      myocardium, respectively. The perfusion defects seen at myocardial perfusion MR
      imaging were significantly smaller than the unstained areas at TTC staining and
      hyperenhanced areas at gadophrin-2- enhanced MR imaging (p < .01). The sizes of
      both the perfusion defect at myocardial perfusion MR imaging and the
      hyperenhanced area at gadophrin-2- enhanced MR imaging correlated well with the
      sizes of unstained areas at TTC staining (r = .64, p = .062 and r = .70, p =
      .035, respectively). CONCLUSION: In this cat model, the perfusion defect revealed
      by myocardial perfusion MR imaging underestimated the true size of acute
      reperfused myocardial infarction. The defect may represent a more severely
      damaged area of infarction and probably has prognostic significance.

PMID- 12514341
TI  - Focal eosinophilic necrosis of the liver in patients with underlying gastric or
      colorectal cancer: CT differentiation from metastasis.
AB  - OBJECTIVE: To determine the helical CT findings which help differentiate between
      focal eosinophilic necrosis (FEN) of the liver and metastasis in patients with
      underlying gastric or colorectal cancer. MATERIALS AND METHODS: In 21 patients
      with underlying gastric and colorectal cancer examined during a recent 18-month
      period, the presence of FEN (n=90) was proven at CT. The diagnosis was verified
      by biopsy in eight patients and by the transient nature of the findings related
      to peripheral eosinophilia (>10%) in the remainder. For comparison, 20
      consecutive patients with pathologically proven hepatic metastasis from gastric
      or colorectal cancer (n=158) were selected. Single-phase helical CT images (7-mm
      collimation, pitch 1:1) were independently analyzed in a random order by two
      blinded readers. The parameters evaluated included the margin (depicted border,
      fuzzy), shape (spherical, non-spherical), attenuation (subtle hypoattenuation,
      hypoattenuation), and the presence or absence of rim enhancement. RESULTS: FEN
      far more frequently showed a fuzzy margin (81%, 84%), subtle hypoattenuation
      (89%, 91%), and a non-spherical shape (84% for both readers) than metastasis, for
      which the respective findings were 6%, 22%; 20%, 39%; and 15%, 23%. Rim
      enhancement was seldom found in FEN (0%, 2%), but was recognized by both readers
      in 40% of metastases. For all parameters, the results were statistically
      significant (p < .01), and showed that both readers correctly differentiated FEN
      from metastasis in 78% of the patients (32/41). Interobserver agreement was, in
      addition, excellent (kappa = 0.66). CONCLUSION: When focal hepatic lesions with a
      fuzzy margin, non-spherical shape and subtle hypoattenuation without rim
      enhancement are found, the possibility of FEN should be considered even in
      patients with underlying gastrointestinal malignancy.

PMID- 12514342
TI  - Saline-enhanced radiofrequency thermal ablation of the lung: a feasibility study
      in rabbits.
AB  - OBJECTIVE: To assess the feasibility and safety of CT-guided percutaneous
      transthoracic radiofrequency ablation (RFA) with saline infusion of pulmonary
      tissue in rabbits. MATERIALS AND METHODS: Twenty-eight New Zealand White rabbits
      were divided into two groups: an RFA group (n=10) and a saline-enhanced RFA
      (SRFA) group (n=18). In the RFA group, percutaneous RFA of the lung was performed
      under CT guidance and using a 17-gauge internally cooled electrode. In the SRFA
      group, 1.5 ml of 0.9% saline was infused slowly through a 21-gauge, polyteflon-
      coated Chiba needle prior to and during RFA. Lesion size and the healing process
      were studied in rabbits sacrificed at times from the day following treatment to
      three weeks after, and any complications were noted. RESULTS: In the SRFA group,
      the mean diameter (12.5+/-1.6 mm) of acute RF lesions was greater than that of
      RFA lesions (8.5+/-1.4 mm) (p < .05). The complications arising in 12 cases were
      pneumothorax (n=8), thermal injury to the chest wall (n=2), hemothorax (n=1), and
      lung abscess (n=1). Although procedure-related complications tended to occur more
      frequently in the SRFA group (55.6%) than in the RFA group (20%), the difference
      was not statistically significant (p = .11). CONCLUSION: Saline-enhanced RFA of
      pulmonary tissue in rabbits produces more extensive coagulation necrosis than
      conventional RFA procedures, without adding substantial risk of serious
      complications.

PMID- 12514343
TI  - Idiopathic synovial osteochondromatosis of the hip: radiographic and MR
      appearances in 15 patients.
AB  - OBJECTIVE: To evaluate the radiographic and MR appearance of idiopathic synovial
      osteochondromatosis of the hip. MATERIALS AND METHODS: Radiographs and MR images
      of 15 patients with idiopathic synovial osteochondromatosis of the hip were
      assessed. The former were analysed in terms of the presence of 1) juxta-articular
      calcified and/ or ossified bodies, 2) osteophytes, 3) bone erosion, 4) juxta
      articular osteopenia, and 5) joint space narrowing, while for the latter,
      analysis focused on 1) the configuration of intra-articular bodies, 2) bone
      erosion, 3) synovial thickening, 4) conglomeration of intra-articular bodies, and
      5) extra-articular extension. RESULTS: At hip radiography, juxta-articular
      calcified and/ or ossified bodies were seen in 12 of the 15 patients (80%), bone
      erosion in eight (53%), osteophytes in seven (47%), juxta-articular osteopenia in
      five (33%) and joint space narrowing in five (33%). In eight patients (53%), MR
      imaging depicted intra-articular bodies of focal low signal intensity at all
      pulse sequences, and areas of isointensity at T1WI and hyperintensity at T2WI. In
      three (20%), intra-articular bodies of focal low signal intensity and areas of
      hyperintensity at all pulse sequences were observed, with areas of iso-intensity
      at T1WI and hyperintensity at T2WI, while in four (27%), intra-articular bodies
      of only focal low signal intensity at all pulse sequences were apparent. Synovial
      thickening was present in 13 patients (87%), bone erosion in 11 (73%),
      conglomeration of the intra-articular bodies in 11 (73%), and an extra-articular
      herniation sac in six (40%). CONCLUSION: The most common radiographic finding of
      synovial osteochondromatosis of the hip was the presence of juxta-articular
      calcified and/ or ossified bodies. MR imaging depicted intra-articular bodies of
      focal low signal intensity at all pulse sequences, with areas of iso-intensity at
      T1WI and hyperintensity at T2WI. In addition, the presence of an extra-articular
      herniation sac was not uncommon.

PMID- 12514344
TI  - Hepatic metastasis from choriocarcinoma: angiographic findings in two cases.
AB  - We report two cases of hepatic metastases from choriocarcinoma in women of
      childbearing age in whom imaging studies performed at presentation revealed the
      presence of liver masses, and who had clinically progressive anemia or
      intraabdominal hemorrhage. CT demonstrated heterogeneously enhanced liver masses.
      Characteristic angiographic findings included hypervascular hepatic masses with
      aneurysmal dilatations of the peripheral hepatic arteries at the arterial phase
      and persistent vascular lakes at the venous phase.

PMID- 12514345
TI  - Retroperitoneal malignant mesenchymoma: a case of mesenchymal mixed tumor with
      osteosarcoma, leiomyosarcoma, liposarcoma and fibrosarcoma.
AB  - Malignant mesenchymoma is an interesting but very rare tumor in which malignant
      differentiation has occurred twice or more. We report a case of retroperitoneal
      malignant mesenchymoma consisting of osteosarcoma, leiomyosarcoma, liposarcoma
      and fibrosarcoma. Abdominal CT showed a large retroperitoneal mass with two
      separate and distinct parts, namely an area of prominent calcification and one of
      clearly enhancing solid components. The mass contained histologically distinct
      tumorous components with no histologic admixure at the interfaces. The densely
      calcified nodule corresponded to osteosarcoma, and the noncalcified clearly
      enhancing nodules to leiomyosarcoma, liposarcoma and fibrosarcoma.

PMID- 12514346
TI  - Unusual perirenal location of a tailgut cyst.
AB  - The authors describe a case in which a tailgut cyst occurred at an unusual
      location in a 22-year-old woman referred for abdominal discomfort and urinary
      frequency. The left abdomen contained a palpable mass, found at imaging studies
      to be a homogeneous, unilocular and cystic, and anterior to the left kidney.
      After surgical excision, it was shown to be a tailgut cyst.

PMID- 12514347
TI  - Non-invasive follow-up evaluation of post-embolized AVM with time-resolved MRA: a
      case report.
AB  - We report the hemodynamic assessment in a patient with cerebral arteriovenous
      malformation using time-resolved magnetic resonance angiography (TRMRA), a non
      invasive modality, and catheter-based digital subtraction angiography (DSA),
      before and after embolization. Comparison of the results showed that TR-MRA
      produced very fast dynamic images and the findings closely matched those obtained
      at DSA. For initial work-up and follow-up studies in patients with vascular
      lesions, TR-MRA and DSA are therefore comparable.

PMID- 12514349
TI  - Is recruitment of foreign nurses a viable or ethical component of strategies to
      solve the current nursing shortage in US?

PMID- 12514351
TI  - First time mothers' views of breastfeeding support from nurses.
AB  - PURPOSE: To gain insights into the perceptions of first-time mothers regarding
      nurses' support of breastfeeding. STUDY DESIGN: Phenomenology. METHOD: Audiotaped
      interviews were conducted with 20 primiparous breastfeeding mothers within the
      first month after giving birth vaginally to healthy term infants. Data analysis
      was concurrent with data collection, and trustworthiness of the data was
      established. RESULTS: Nurses provided emotional, informational, and tangible
      support. Nonsupportive behaviors were also identified, including a sense that the
      nurse was in a hurry, failed to offer breastfeeding assistance, and was
      inflexible while working with the mother and infant. CLINICAL IMPLICATIONS:
      Nurses can contribute significantly to the successful initiation of and
      continuation of breastfeeding, and provide new mothers with the confidence and
      reassurance critical for breastfeeding success.

PMID- 12514352
TI  - The lived experience of miscarriage after infertility.
AB  - PURPOSE: To describe women's experiences of miscarriage after infertility
      treatments. Published studies in which fertile women were interviewed after
      miscarriage have found that the women universally look to another pregnancy as
      the solution to their grief. However, for women undergoing infertility
      treatments, the possibility of another pregnancy is not a certainty. Despite
      this, little is known about the unique experience of this group of women.
      Appropriate interventions based on evidence require research to discover these
      women's needs. DESIGN: Phenomenology. METHOD: Eight women who had experienced
      miscarriage after infertility were interviewed. Interviews were audiotaped and
      transcribed verbatim. Data saturation guided the sample size. Colaizzi's methods
      for phenomenologic analysis were used. Analyzed data were brought back to the
      women for fact checking and to ensure trustworthiness and reliability of the
      data. RESULTS: Themes included : going back to "square one," an inner struggle
      between hope and hopelessness for future fertility, running out of time,
      anger/frustration, lack of understanding by others, guilty feelings, feeling
      alone/numb with their grief, and gaining strength from adversity. CLINICAL
      IMPLICATIONS: This study provides a first glimpse of women who miscarry after
      infertility treatments, and demonstrates that they feel profoundly alone, and
      grieve intensely. They worry that they caused the miscarriage, and find it
      difficult to hope that they will ever become pregnant again. Several women
      described being hospitalized for their miscarriage on postpartum units. This was
      unbearable for them, and should remind all of us in healthcare that this type of
      unthinking treatment of women who miscarry after infertility is not acceptable.

PMID- 12514353
TI  - Unintended pregnancies: a call for nursing action.
AB  - Unintended pregnancies occur in all age groups and socioeconomic strata of our
      society and represent significant social, medical, and economic costs. Nearly 50%
      of all pregnancies in the United States are classified as unintended, and
      approximately 48% of all women ages 15 to 44 have experienced at least one
      unintended pregnancy. Contributors to unintended conceptions in the U.S. included
      barriers to accessing contraception, fears about using it, errors in use, and
      lack of back-up plans when errors in use occur. As important proponents of
      women's health, nurses are in an ideal position to address each of these
      contributors to unintended pregnancy through health promotion activities
      including patient education and counseling, through public policy advocacy, and
      through a commitment to a research agenda.

PMID- 12514354
TI  - Characteristics of African American women caregivers of children with asthma.
AB  - PURPOSE: To describe the attributes and characteristics of African American women
      who were the primary caregivers of children with asthma. METHODS: Descriptive
      qualitative ethnography. Data collection consisted of formal interviews,
      participant observation, and fieldnotes. Each study participant was formally and
      informally interviewed (audiotaped) during a 1-year period. The researchers also
      observed and participated in family activities in various naturalistic settings.
      RESULTS: Six themes emerged that depict the characteristics of these women: (1)
      Knowledge about the child's asthma; (2) Gatekeepers to the child's care; (3)
      Being religious; (4) Support; (5) Roles as teacher, counselor, and advisor to the
      child; and (6) Self-sufficiency and industriousness. CLINICAL IMPLICATIONS:
      Nurses should use the information in this study to examine the ways in which they
      interact with caregivers of asthmatic children. The caregivers personal beliefs,
      need for information, and previous experiences with asthma and family illness
      should be assessed. These mothers and grandmothers should be respected as the
      gatekeeper to the family's healthcare. Nurses should be nonjudgmental and
      supportive of caregivers when they express their religious beliefs and practices.
      Nurses who understand how mothers cope can reinforce these coping skills and
      provide better nursing care.

PMID- 12514355
TI  - Culture & spirituality as an integrated concept in pediatric care.
AB  - The purpose of this article is to propose an integrated approach to culture and
      spirituality in pediatric care. In the spirit of sensitive and respectful
      communication with patients, pediatric nurses have become increasingly concerned
      with the child's and family's culture, spirituality, and religion. As a result,
      various approaches and models have been created to help nurses initiate
      discussions surrounding these topics. These models have given rise to
      categorizations of culture, spirituality, and religion. It is important for
      pediatric nurses to understand that while delineations can be made, there are
      also many intersecting factors that make separation of these issues difficult and
      perhaps unnecessary for the purpose of culturally sensitive communication.
      Pediatric nurses should, perhaps, focus instead on understanding the individual
      child's or family's traditions, values, and beliefs and how these dimensions
      impact the health of the child. This article suggests three areas that can be
      used as an organizing framework for pediatric nurses to broach culturally
      sensitive issues within the context of pediatric primary healthcare: (1) Family
      beliefs/values, (2) Family daily practices, and (3) Community involvement.

PMID- 12514356
TI  - Women in recovery discuss parenting while addicted to cocaine.
AB  - PURPOSE: To identify what women recovering from cocaine addiction think is needed
      of them to be good parents. DESIGN: An exploratory descriptive design using in
      depth, semistructured interviews, conducted in the woman's home or in a treatment
      center. Demographics and pregnancy history were collected during the interview. A
      convenience sample of 11 mothers recovering from cocaine addiction participated.
      RESULTS: Content analysis was used to analyze the interview data. Five themes
      emerged from the interviews: lack of structure, abandonment, impatience/anger,
      lack of parenting knowledge, and repeating dysfunctional patterns from family of
      origin. CLINICAL IMPLICATIONS: Women addicted to cocaine who are parenting
      children need strong encouragement from the healthcare system to begin a recovery
      program and also to gain parenting skills. Discussions of child development and
      parenting stresses should be included during the recovery process from addiction
      because lack of parenting knowledge might be a major barrier for them. This study
      can help nurses to provide improved care for women who are parenting children
      while using cocaine or other drugs.

PMID- 12514357
TI  - Synchronizing with standard time and atomic clocks.

PMID- 12514358
TI  - Stuve-Wiedemann syndrome in children surviving infancy: clinical and radiological
      features.
AB  - We report three children from two inbred Arab families with Stuve-Wiedemann
      syndrome who have survived the first year of life (ages are 6 years, 2.8 years
      and 2 years). All exhibited a characteristic phenotype resembling that described
      by Chen et al.[(2001). Am J Med Genet 101:240-245]. In all three children the
      skeletal abnormalities progressed to severe bowing of the long bones with
      prominent joints and severe spinal deformity. Neurological symptoms were present
      in all of them. These included temperature instability with excessive sweating,
      reduced pain sensation with repeated injury to the tongue and limbs, absent
      corneal reflexes and a smooth tongue. Mentality was normal in all of them.
      Radiological changes included under tubulation of the diaphyses, rarefaction and
      striation of metaphyses, destruction of the femoral heads and spinal deformity.
      We confirm that survival in this syndrome is possible and that the prognosis
      improves after the first year of life. This should be taken into consideration
      when counselling parents of affected children. This report further supports the
      existence of a characteristic phenotype in Stuve-Wiedemann syndrome survivors
      which include, in addition to the skeletal abnormalities and distinctive
      radiological features, neurological symptoms reminiscent of dysautonomia.

PMID- 12514359
TI  - Midface hypoplasia, obesity, developmental delay and neonatal hypotonia in two
      brothers.
AB  - We describe two brothers born to consanguineous parents, who presented with
      hypotonia and hypoglycaemia in the neonatal period and later developed obesity
      and developmental delay. They had brachydactyly and similar facial features
      including a prominent forehead, low nasal bridge, midface hypoplasia, full lips,
      a small mouth, and small, low set ears with overfolded helices. Their sister had
      mild learning disabilities. No additional anomalies were found, and metabolic
      investigations including peroxisomal functions gave normal results. We suggest
      the patients have a hitherto unreported condition, with an autosomal or X-linked
      mode of inheritance.

PMID- 12514360
TI  - Siblings with Bohring-Opitz syndrome.
AB  - We describe a brother and sister with Bohring-Opitz syndrome and suggest that
      autosomal recessive inheritance may occur in this condition.

PMID- 12514361
TI  - Dyshormonogenic hypothyroidism with normal neurological development, unexplained
      short stature and facial anomalies in three siblings.
AB  - We report three members of a family with clinical and laboratory features,
      consistent with dyshormonogenic hypothyroidism, with an autosomal recessive
      pattern of inheritance. Two had primary hypothyroidism with normal Tc(99m)
      thyroid scans, presenting with growth delay at ages of 7.5 and 2, and one had
      hypoplasia of the right lobe of the thyroid with left lobe hemiagenesis and low
      thyroid uptake in iodide thyroid scan, diagnosed at 14 months. They had slender
      facies with nasal retrognathic mandible and a prominent bridge. They had
      reasonably normal intellectual development despite delayed onset of treatment.
      Despite advancement of bone age with treatment the patients remained
      significantly short. Possible differential diagnoses are dyshormonogenic
      hypothyroidism, especially hyporesponsiveness to thyrotropin and short stature
      that may be due to an abnormal gene in this family.

PMID- 12514362
TI  - Molecular cytogenetic characterization of a de novo unbalanced translocation
      leading to trisomy 17q25-->qter and monosomy 18p11.3-->pter in a girl with
      dysmorphic features.
AB  - An 18-year-old, gravida 1 underwent percutaneous umbilical blood sampling (PUBS)
      because of positive triple screen, oligohydramnios and markedly short fetal
      bones. Chromosome analysis showed an abnormal chromosome 18 with unidentified
      chromatin at the end of the p-arm. Parental karyotypes were normal. FISH analyses
      with wcp18 showed additional material of unknown origin on the derivative
      chromosome 18. Further FISH analysis with subtelomeric probes showed normal
      signals for the long arm of chromosome 18 (18q23) while no signals were observed
      for the short arm (18p11.32). These findings were confirmed using a YAC probe
      from the short arm of 18. The infant was delivered at 30 weeks of gestation. At
      age 3 months, she was developmentally delayed and has multiple dysmorphic
      features. Further molecular cytogenetic studies including M-FISH and subtelomere
      probes showed that the additional material on chromosome 18 consisted of the
      distal 17q25-->qter region. Based on these studies the karyotype has been
      interpreted as 46,XX,der(18)t(17;18)(q25;p11.32). To the best of our knowledge,
      this is the first report of partial monosomy 18p and partial trisomy 17q in a
      patient with no major CNS malformations. This case shows the importance of
      molecular cytogenetic techniques in detailed characterization of de novo
      chromosome rearrangements.

PMID- 12514363
TI  - Familial cryptic translocation with deletion 4q33-->4qter and duplication 7q34-
      >7qter in brothers with mental retardation, macrocephaly and iris coloboma.
AB  - The association of moderate mental retardation, behavioural problems,
      macrocephaly, dysmorphic features with iris coloboma, and supernumerary nipples
      was observed in two brothers with a terminal deletion 4q33-->4qter and a terminal
      duplication 7q34-->7qter. The aberration was detected by subtelomere FISH
      screening and (probably) resulted from a cryptic familial translocation
      (4;7)(q33;q34).

PMID- 12514364
TI  - Fryns "Anophthalmia-Plus" syndrome associated with developmental regression.
AB  - We report a boy with a nasal deformity, choanal atresia, bifid uvula, severe
      bilateral microphthalmia and a facial cleft who showed regression of development
      at the age of 2 years with subsequent improvement. We suggest he represents a
      further case of the rare Fryns "Anophthalmia-Plus" syndrome.

PMID- 12514365
TI  - SHORT syndrome.
AB  - We describe a mother and her son with short stature, progeroid facies, Rieger
      anomaly, teething delay, and mild developmental retardation, particularly speech
      delay, which are characteristic features of the SHORT syndrome. An additional
      sign of all described patients is the slight build with lack of subcutaneous fat.
      Resistance to insulin was suggested by an oral glucose tolerance test in the
      mother, whereas the test was normal in the index patient at the age of 2 years 2
      months. We review the literature and discuss the name-giving symptoms critically.
      Five familial cases in different generations, equally affected male and female
      patients and male-to-male transmission point to an autosomal dominant mode of
      inheritance.

PMID- 12514366
TI  - Lumbopedal skin pedicle in an infant with the amniotic band syndrome: a
      Disorganization-like defect?
AB  - A female infant is presented in whom anomalies not commonly seen in amniotic band
      syndrome (ABS) included non-anatomic lumbopedal union by a skin pedicle,
      anorectal malformation, meningocele, vertebral segmentation defects, longitudinal
      limb defects, vestigial feet and skin papillae. The unusual, non-band related
      malformations in the proposita showed similarity to the mouse mutant
      Disorganization (Ds). This report, supports the suggestion that Ds-like mutations
      may cause some cases with apparent ABS associated with "skin pedicles".

PMID- 12514367
TI  - Sensorineural hearing loss and enamel hypoplasia with subtle nail findings:
      another family with Heimler's syndrome.
AB  - We report a pair of siblings who exhibit findings similar to those described in
      Heimler's syndrome, namely sensori- neural hearing loss diagnosed after the first
      year of life and enamel hypoplasia with normal primary dentition. Nail findings
      of Beau's lines and leukonychia which were described in the previous cases are
      absent to questionable in our patients. Our findings support the theory of
      autosomal recessive inheritance for Heimler's syndrome. To our knowledge there
      have been only three cases reported previously and the gene location has yet to
      be determined.

PMID- 12514368
TI  - Transposition of external genitalia and associated malformations.
AB  - We report three Egyptian boys from three different families born with penoscrotal
      transposition (PST). None of them fell into categories of known syndromes,
      associations, sequences or chromosome disorders. Other malformations observed
      included renal, genital, cardiovascular and limb defects. Although the occurrence
      of most reported cases of PST are sporadic, three families with affected sibs
      have been reported in the literature where parental consanguinity was not
      specified. Parental consanguinity is present in two of our three cases with young
      parental age suggesting the possibility of an autosomal recessive pattern of
      inheritance. A history of maternal hormonal treatment early in pregnancy in one
      of our cases may suggest a role of teratogenic agents. We conclude that PST may
      represent only a part of a wide spectrum of anomalies resulting from a major
      insult occurring during early embryonic development and is of heterogeneous
      etiology.

PMID- 12514369
TI  - Familial cerebro-costo-mandibular syndrome: a case with unusual prenatal findings
      and review.
AB  - Cerebro-costo-mandibular syndrome is characterized by the Pierre-Robin anomaly,
      multiple rib defects and the occasional occurrence of intellectual impairment.
      Over 60 cases have been reported, nearly half of which are familial. We report an
      infant and her father with typical features of CCMS. The child was diagnosed on
      prenatal ultrasound and was found to have the previously unreported prenatal
      finding of an omphalocoele. Twenty-eight cases of familial CCMS are reviewed.
      Families suggestive of autosomal recessive and autosomal dominant inheritance are
      not distinguishable on the basis of clinical manifestations.

PMID- 12514370
TI  - Anterior segment dysgenesis and absent lens caused by amniotic bands.
AB  - A male infant is described with anterior segment dysgenesis and absent lens
      caused by amniotic bands.

PMID- 12514371
TI  - Smith-Magenis syndrome and cyanotic congenital heart disease: a case report.
AB  - We report a male newborn infant of Chinese descent with the Smith-Magenis (SMS)
      syndrome who presented with a severe cyanotic congenital heart disease. This
      report adds pulmonary atresia and ventricular septal defect to the spectrum of
      cardiac defects seen in SMS.

PMID- 12514372
TI  - Three craniosynostotic patients with tracheal sleeve.
AB  - The gene was analysed in three craniosynostotic patients with a tracheal sleeve
      and other abnormalities. Although the majority of mutations are found in either
      exons IIIa or IIIc, this was not found in this study. It may be that patients
      with a tracheal sleeve are genetically heterogeneous.

PMID- 12514373
TI  - Regular tracheostomy tube changes to prevent formation of granulation tissue.
AB  - OBJECTIVES/HYPOTHESIS: Tracheostomy is a commonly performed operative procedure
      that has been described since 2000 B.C. The early indications for tracheostomy
      were for upper airway obstruction, usually occurring in young people as a result
      of an infectious process. Recently, tracheostomies are more commonly performed in
      the critically ill patient to assist in long-term ventilatory support.
      Granulation tissue at the stoma and the trachea has been described as a late
      complication resulting in bleeding, drainage, and difficulty with maintaining
      mechanical ventilatory support. STUDY DESIGN: The present report is of an
      observational study of a newly implemented policy that required regular changing
      of tracheostomy tubes. Comparable groups of patients were compared before and
      after this procedural change to document complications. Data collection consisted
      of chart reviews of all admissions for 1 year before the policy change and the
      subsequent 2 years. Complication rates were compared using standard statistical
      techniques. METHODS: A policy change was instituted that required all
      tracheostomy tubes to be changed every 2 weeks in conjunction with a detailed
      evaluation of the tracheostomy stoma. Charts were reviewed the year before the
      change in policy and in the subsequent 2 years to determine the incidence of
      granulation tissue requiring operative intervention. RESULTS: The number of
      patients requiring surgical intervention secondary to granulation tissue showed a
      statistically significant decrease (P =.02). A review of policies and procedures
      from the six largest hospitals in southeastern Michigan had no recommendations
      for routine tracheostomy tube changes. CONCLUSIONS: A policy requiring a routine
      change of tracheostomy tubes results in fewer complications from granulation
      tissue. Tracheostomy tube changes to prevent granulation tissue and its
      complications.

PMID- 12514374
TI  - Suspension laryngoscopy for endotracheal stenting.
AB  - OBJECTIVES/HYPOTHESIS: Airway stents have recently been used to establish and
      maintain patent airways in patients with malignant central airway obstruction,
      but insertion modalities remain controversial to date. The study seeks to
      determine the role of suspension laryngoscopy in interdisciplinary airway
      stenting. STUDY DESIGN: Retrospective, single-institution analysis of a case
      series treated by a multidisciplinary airway team. METHODS: Ninety-three
      consecutive patients with malignant obstruction of the trachea and/or
      tracheobronchial bifurcation underwent endotracheal stenting through a suspension
      laryngoscopy approach for the relief of impending respiratory distress.
      Feasibility, mortality, survival, and complications were analyzed as main outcome
      measures. RESULTS: Stenting through a suspension laryngoscopy approach was
      feasible 91 of 93 patients (97.8%). Fifteen patients needed repeated stenting,
      and in all, 121 stents were implanted during the observation period. This
      approach allowed for the repeated insertion of rigid bronchoscopes of graded
      sizes to establish an airway and for precise stent positioning. Optical
      instruments and stent introducer systems could easily be used while adequate
      ventilation was continuously maintained. Silicone stents of maximal size were
      inserted without injury of the vocal cords during intubation. Median survival for
      all patients was 8 months. No intraoperative airway complications were observed,
      and no patient died secondary to stenting. CONCLUSIONS: Suspension laryngoscopy
      and jet ventilation provide an ideal setting for the precise placement of
      tracheal and bifurcation airway stents. Laryngologists should actively
      participate in interdisciplinary airway stenting programs.

PMID- 12514375
TI  - Laryngotracheal injury after percutaneous dilational tracheostomy in cadaver
      specimens.
AB  - OBJECTIVE: To evaluate the stoma and surrounding insertion site for common
      laryngotracheal injury patterns after percutaneous dilational tracheostomy that
      may contribute to clinically significant tracheal stenosis. STUDY DESIGN:
      Preliminary prospective cadaver study. METHODS: A preliminary prospective cadaver
      study was performed in which percutaneous dilational tracheostomy (Ciaglia Blue
      Rhino kit) was placed in six fixed cadaveric specimens. Laryngotracheal segments
      were harvested. Two independent evaluators graded cadaver features and
      characteristic injuries in laryngotracheal specimens the tracheal site of stoma
      placement was identified. Cadaver features evaluated included gender, obesity,
      and ease of landmark identification. Mucosal and cartilage injuries were
      evaluated on a scale of 0 to 4, with 4 representing severe comminuted injuries
      beyond the intended stoma site. RESULTS: Accurate prediction of tracheal
      placement was achieved in only three (50%) of the specimens. In the remaining
      cadavers, one stoma site was placed higher than intended (16%) and two sites were
      lower than intended (33%). Mucosal injury was most severe at the anterior
      internal surface of the trachea with all specimens sustaining tears beyond one
      tracheal ring (mean mucosal injury score, 3.5). Cartilaginous injury was severe
      in five of six specimens (83%) that sustained multiple comminuted injuries to two
      or more adjacent rings (mean cartilage injury score, 3.34). Cricoid comminutions
      and a posterior membranous tracheal wall injury were each found in one specimen.
      CONCLUSIONS: Laryngotracheal injuries found after percutaneous dilational
      tracheostomy in the study indicated that severe damage to mucosa and cartilage
      surrounding the intended stoma site occurs at the time of placement. These
      injuries may contribute to clinically significant tracheal stenosis preventing
      decannulation in patients undergoing percutaneous dilational tracheostomy. Two
      case studies that support this hypothesis are also presented.

PMID- 12514376
TI  - The safety of flexible endoscopic evaluation of swallowing with sensory testing
      in an outpatient otolaryngology setting.
AB  - OBJECTIVE: To study the safety of flexible endoscopic evaluation of swallowing
      with sensory testing in a private otolaryngology office setting. STUDY DESIGN:
      Five parameters were prospectively evaluated. These included airway compromise,
      epistaxis, change in heart rate, level of discomfort, and patient's willingness
      to repeat the examination in the future. METHODS: All persons undergoing flexible
      endoscopic evaluation of swallowing with sensory testing between July 1, 1999,
      and June 30, 2001, were prospectively evaluated. A flexible fiberoptic endoscope
      with a specially designed air port channel was passed transnasally (without
      topical anesthesia or nasal constriction) into the more patent nostril.
      Nasopharyngeal and laryngeal anatomy were first evaluated. Laryngopharyngeal
      sensory and motor function were then assessed, followed by a comprehensive
      swallowing evaluation. Five test parameters were examined during each study.
      Descriptive statistics were calculated. RESULTS: Three hundred forty-nine
      consecutive examinations in 305 adult patients with dysphagia were performed
      during the study period. Mild epistaxis occurred in four patients (1.1%). There
      were no episodes of airway obstruction or laryngospasm. There was no
      statistically significant difference between the average pretest and post-test
      heart rates; no patients became symptomatically bradycardic or tachycardic. The
      discomfort ratings were as follows: 44 patients (12.6%) rated the overall
      discomfort of the test as none, 169 (48.4%) thought it was mild, 110 (31.5%)
      described moderate discomfort, and 26 (7.5%) said it was severe. Three hundred
      forty-two (98%) of the patients would repeat the test in the future; seven
      patients (2%) said that they would not. CONCLUSIONS: Flexible endoscopic
      evaluation of swallowing with sensory testing is a safe, well-tolerated procedure
      to objectively evaluate patients with dysphagia when performed by an experienced
      speech-language pathologist with an otolaryngologist in attendance in an
      outpatient office setting.

PMID- 12514377
TI  - Human septal chondrocyte redifferentiation in alginate, polyglycolic acid
      scaffold, and monolayer culture.
AB  - OBJECTIVES/HYPOTHESIS: Tissue engineering laboratories are attempting to create
      neocartilage that could serve as an implant material for structural support
      during reconstructive surgery. One approach to forming such tissue is to
      proliferate chondrocytes in monolayer culture and then seed the expanded cell
      population onto biodegradable scaffolds. However, chondrocytes are known to
      dedifferentiate after this type of monolayer growth and, as a result, decrease
      their production of cartilaginous extracellular matrix components such as
      sulfated glycosaminoglycans. The resultant tissue lacks the biomechanical
      properties characteristic of cartilage. The objective of the study was to
      determine whether different culture systems could induce monolayer-expanded human
      septal chondrocytes to redifferentiate and form extracellular matrix. STUDY
      DESIGN: Laboratory research. METHODS: Chondrocytes were isolated from human nasal
      septal cartilage of five donor patients (age, 35.8 +/- 9.3 y). Cell populations
      were seeded at low density (30,000 cells/cm2) into monolayer culture and expanded
      for 4 to 6 days. Following trypsin release, chondrocytes were placed into three
      different systems for neocartilage formation: alginate beads, polyglycolic acid
      scaffolds, and monolayer. After 7 and 14 days of growth, neocartilage was
      analyzed using histological and quantitative biochemical assessment of
      cellularity (Hoechst 33258 assay) and sulfated glycosaminoglycan content
      (dimethyl methylene blue assay). RESULTS: Histologically, alginate beads
      contained spherical chondrocytes surrounded by dense extracellular matrix, an
      appearance similar to that of native cartilage. In contrast, polyglycolic acid
      scaffolds and monolayer cultures contained elongated cells with scant staining
      for matrix sulfated glycosaminoglycans, which are features that are
      characteristic of dedifferentiated chondrocytes. Biochemical analysis
      demonstrated a lower level of cell proliferation (P <.001) in scaffolds (+52%
      over baseline) and alginate (+96% over baseline) than in monolayer (+366% over
      baseline), as well as a higher content of sulfated glycosaminoglycans per cell (P
      <.001), after 14 days of growth in alginate culture than in either polyglycolic
      acid scaffolds (19-fold difference) or monolayer (98-fold difference).
      CONCLUSIONS: Of the systems compared, monolayer-expanded human septal
      chondrocytes demonstrated the greatest accumulation of sulfated
      glycosaminoglycans per cell when grown in alginate beads. Future research on
      cartilage tissue engineering may use alginate culture for reverting
      dedifferentiated cells back to the chondrocytic phenotype.

PMID- 12514378
TI  - Electrocochleography and intranasal allergen challenge as investigational tools
      in patients with inhalant allergy and Meniere's disease.
AB  - OBJECTIVES: To expand on a prior study investigating the relation between
      inhalant allergy and Meniere's disease using electrocochleography and to present
      data from five patients heretofore unmentioned in previous reports. STUDY DESIGN:
      Prospective study of five patients identified with Meniere's disease and inhalant
      allergy in the practices of two faculty otolaryngologists. METHODS: Patients were
      tested twice using electrocochleography: once as a baseline and again 20 minutes
      following intranasal challenge with the allergen to which they were most
      sensitive. RESULTS: Three patients had no prior history of immunotherapy, and all
      were found to have a >15% increase in summating potential (SP)/action potential
      (AP) ratio after antigen challenge. However, only one of these patients developed
      audiovestibular symptoms. Two patients had a history of immunotherapy. One of
      these patients was tested using three different antigens to which she was highly
      sensitive on skin testing, one of which provoked audiovestibular symptoms on
      environmental exposure. Postchallenge electrocochleography, however, demonstrated
      normal SP/AP ratios with only one antigen causing a >15% increase. The other
      patient had elevated SP/AP ratios both before and after challenge and developed
      no audiovestibular symptoms despite a >15% increase. CONCLUSIONS: Previous work
      using this investigational tool has identified that all patients with a normal
      electrocochleography were asymptomatic from an audiovestibular standpoint at the
      time of postchallenge testing. An elevated SP/AP was not reliably correlated with
      audiovestibular symptoms in this group of patients. Further investigation in this
      area will examine the utility of using the variability of the SP and AP to
      predict audiovestibular symptoms.

PMID- 12514379
TI  - Congenital dacryocystocele associated with intranasal cysts: diagnosis and
      management.
AB  - OBJECTIVE: To improve the diagnostic and therapeutic database for congenital
      dacryocystoceles. STUDY DESIGN/METHODS: Retrospective case study of 10 patients
      with dacryocystoceles treated in an academic integrated tertiary care practice.
      Management and outcomes are compared to previous reports in the literature.
      RESULTS: Between the years 1990 and 2001, 10 patients were diagnosed with
      dacryocystoceles. Seven were females, and 3 were males. Age ranged from 1 to 75
      days. Nine of 10 had a unilateral dacryocystocele, and 1 had bilateral
      dacryocystoceles. Epiphora was reported in 8 patients. Preoperatively,
      dacryocystitis, facial cellulitis, or both were present/developed in 2 patients.
      Symptoms of airway obstruction were present in 3 neonates. Surgery was performed
      in 9 of 10 patients and was a combined ophthalmology/otolaryngology surgery in 7
      cases. Two patients were treated with probing only. Intranasal cysts were
      identified in all 7 patients who underwent a combined approach. Three of 7
      patients had bilateral intranasal cysts. Follow-up ranged from 9 months to 10
      years (mean, 5 years). Complete resolution was observed in 9 patients. One
      patient had postoperative nasolacrimal duct obstruction 2 months postoperatively,
      presenting with mucopurulent drainage and cellulitis. The existing literature
      often suggests conservative management as a treatment option. CONCLUSION: True
      dacryocystoceles are a relative rarity. The literature describes a variable
      natural course of these lesions with resultant controversy in their management.
      The current results demonstrate successful treatment in 6 of 7 patients with an
      early combined surgical approach and 2 of 2 patients treated by probing alone.
      The high failure rate with conservative management, reported in the literature,
      supports early surgical intervention.

PMID- 12514380
TI  - Isolated inverting papilloma of the sphenoid sinus.
AB  - OBJECTIVES/HYPOTHESIS: Primary inverting papilloma of the sphenoid sinus is rare.
      We present a case of inverting papilloma with isolated involvement of the
      sphenoid sinus and discuss the incidence, clinical presentation, radiographic
      features, histological findings, and management of patients with this disease.
      STUDY DESIGN: Case report. METHODS: The medical records, films, and pathology
      slides of a patient with isolated inverting papilloma of the sphenoid sinus seen
      at University of California Los Angeles Medical Center were reviewed. The
      clinical presentation, radiographic features, histopathological findings,
      treatment, and outcome of the case were examined. RESULTS: A single case of
      inverting papilloma with isolated involvement of the sphenoid sinus is presented.
      Headache and diplopia were the presenting complaints, as is often seen with other
      isolated sphenoid sinus lesions. Endoscopic intranasal sphenoid sinusotomy was
      performed, and no evidence of recurrent disease has been seen after 6 months of
      follow-up. CONCLUSIONS: Isolated inverting papilloma of the sphenoid sinus is a
      rare phenomenon. In contrast to the vast majority of cases that present with
      nasal complaints (i.e., unilateral nasal obstruction, epistaxis) because of
      involvement of the lateral nasal wall, the clinical presentation of inverting
      papillomas confined to the sphenoid sinus is often nonspecific and insidious,
      with visual deficits being the predominant feature. Nevertheless, functional
      endoscopic intranasal sphenoidotomy remains an effective mode of treatment for
      patients with these lesions.

PMID- 12514381
TI  - Cochlear implantation in patients with auditory neuropathy of varied etiologies.
AB  - OBJECTIVES/HYPOTHESIS: Auditory neuropathy is a relatively recently described
      pattern of hearing loss characterized by preservation of outer hair cell function
      despite absent brainstem auditory evoked responses. Intact outer hair cell
      function is demonstrated by the presence of otoacoustic emissions and/or a
      measurable cochlear microphonic on electrocochleography, whereas no synchronous
      neural activity (absent action potentials) is seen on acoustically evoked
      brainstem auditory evoked response testing. The study reviews the authors'
      experience with six patients diagnosed with auditory neuropathy, four of whom
      have undergone cochlear implantation. MATERIALS AND METHODS: A retrospective
      review of all medical and audiological charts at the University of Virginia
      Hospitals (Charlottesville, VA) was performed to identify patients who have
      undergone cochlear implantation or have been diagnosed with auditory neuropathy,
      or both. RESULTS: Six patients with hearing loss attributable to auditory
      neuropathy were identified, four of whom have undergone cochlear implantation.
      Causes varied, including congenital, infectious, and idiopathic origins. Adults
      demonstrated subjective auditory perception on promontory stimulation, whereas no
      repeatable brainstem auditory evoked response waveforms could be demonstrated on
      pediatric promontory stimulation testing. Patients with implants demonstrated
      implant-evoked brainstem auditory evoked responses and improved audiological
      performance. CONCLUSIONS: The six cases presented in the study represent varied
      causes and, probably, varied sites of lesions of auditory neuropathy. Promontory
      stimulation has been valuable, particularly in adults. Cochlear implantation
      allows the opportunity to provide a supraphysiological electrical stimulation to
      the auditory nerve, with the hope of reintroducing synchronous neural activity.
      Greater confidence and enthusiasm for cochlear implantation in appropriately
      selected patients with auditory neuropathy are gained through experience with
      such diverse cases.

PMID- 12514382
TI  - Management of cerebrospinal fluid leaks involving the temporal bone: report on 92
      patients.
AB  - OBJECTIVE: To investigate the success of different surgical and nonsurgical
      techniques in the management of cerebrospinal fluid otorrhea or otorhinorrhea.
      STUDY DESIGN: Retrospective case analysis. METHODS: Ninety-two patients with
      confirmed diagnosis of cerebrospinal fluid otorrhea or otorhinorrhea treated at
      our institution between 1976 and 1998 were followed up long-term by retrospective
      chart review and patient interviews. RESULTS: Conservative treatment was
      successful in most cases of cerebrospinal fluid otorrhea or otorhinorrhea
      resulting from head injury (26 of 29 patients). In contrast, surgical
      intervention was required in all but 1 of 53 patients with cerebrospinal fluid
      otorrhea or otorhinorrhea caused surgically. The primary operative success rate
      was 76.9%. When relapse occurred, the interval ranged from 0 days to 24 months
      (mean interval, 3.9 mo; median, 1.3 mo). All leaks requiring surgery eventually
      were closed successfully. Surgical results were chronologically dependent. Before
      1989, 11 failures occurred in 37 primary procedures. After 1989, only 4 failures
      occurred in 28 primary procedures. Of seven patients undergoing primary dural
      closure alone, three (43%) had recurrence of the leak. Closure rates were highest
      among patients in whom a multilayer technique for leak closure was used:
      combining a primary graft or sealing material such as bone wax, free muscle, or
      fascia for closure of the defect with additional autologous free grafts or
      allogenic materials. This resulted in a 2-year closure rate of 100% compared with
      a 2-year rate of 75.4% for patients whose primary closure was supported by a
      single layer of autologous or allogenic material (P =.034). Fibrin glue with
      primary closure alone did not have additional benefit. Postoperative meningitis
      occurred in two patients and was treated without sequelae. CONCLUSIONS:
      Conservative treatment should be reserved for cerebrospinal fluid otorrhea or
      otorhinorrhea resulting from head injury. Postoperative and nontraumatic
      cerebrospinal fluid otorrhea or otorhinorrhea should have early operative
      intervention. A multilayer technique combining allogenic materials with free
      autologous grafts is recommended.

PMID- 12514383
TI  - Neuropsychological testing in the screening for cochlear implant candidacy.
AB  - OBJECTIVE: To demonstrate the utility of neuropsychological assessment in the
      screening process for pediatric cochlear implant candidacy. STUDY DESIGN:
      Prospective and ongoing evaluation of children with profound bilateral hearing
      loss using age-specific neuropsychological test batteries. METHODS: Eighteen
      children who met audiological criteria for cochlear implantation were evaluated
      by two age-specific neuropsychological tests. The Vineland Adaptive Behavior
      Scales survey assesses several domains of behavioral functions (communication,
      daily living skills, socialization, and gross motor skills). The Mullen Scales of
      Early Learning assess the child's visual perception, speech and language, and
      motor abilities. The Leiter International Performance Scale-Revised assesses
      intellectual ability. RESULTS: All patients underwent the Vineland Adaptive
      Behavior Scales survey. Overall scores were lower than normative means with a
      mean composite score in the 7th percentile. In addition, there was a strong
      inverse correlation between score and age of testing. Ten children were assessed
      using the Mullen Scales of Early Learning, and, again, there was a strong inverse
      correlation between score and age of testing. Intellectual ability was assessed
      in seven children using the Leiter International Performance Scale-Revised and
      was found to be lower than normative means with a mean score in the 13th
      percentile. CONCLUSIONS: Neuropsychological testing of profoundly deaf children
      provides a detailed and accurate assessment of the child's cognitive, behavioral,
      and motor functions. The profoundly deaf child does not develop at the same rate
      as normal children in cognitive and behavioral domains. Neuropsychological
      testing is a useful tool for screening for cochlear implant candidacy and has the
      potential to track changes before and after implantation.

PMID- 12514384
TI  - Endoscopic staple diverticulostomy for recurrent Zenker's diverticulum.
AB  - OBJECTIVES: The purpose of this study was to evaluate the technical feasibility,
      effectiveness, and morbidity of using endoscopic staple diverticulostomy (ESD) as
      treatment for Zenker's diverticulum (ZD) recurring after either prior endoscopic
      treatment or external diverticulectomy or diverticulopexy. STUDY DESIGN: A
      retrospective review of a case series of 18 patients with recurrent ZD. METHODS:
      All patients cared for with ZD were evaluated to identify those patients with
      recurrent ZD. The clinical records of patients with recurrent ZD were reviewed
      for: demographics, prior treatment, time to recurrence, factors associated with
      recurrence, technical feasibility of treatment, complications, effectiveness and
      duration of symptom relief. RESULTS: Between March 1995 and July 2001, a total of
      127 consecutive patients with ZD received care. Eighteen of these patients were
      treated for recurrent ZD: nine treated originally by ESD, and nine by external
      approach (seven by diverticulectomy and two by diverticulopexy), with three of
      these patients treated twice. Seventeen patients had partial or complete relief
      of symptoms after their initial treatment, with recurrence of symptoms noted 0 to
      60 months later. Specific factors associated with recurrence of symptoms were
      identified in only one patient. Treatment of recurrent ZD by ESD was technically
      feasible in 16 of the patients. Complete or improved symptom relief has been
      reported by 16 of the patients after revision ESD, with follow-up from 9 to 69
      months. No significant treatment complications occurred. Fifteen patients resumed
      clear liquid diet on the day of surgery, and one on the day after surgery. All
      patients were discharged from the hospital by the second postoperative day (mean
      = 0.6 d). CONCLUSIONS: ESD is an effective, technically feasible, and safe
      treatment for patients with ZD recurring after prior endoscopic or external
      treatment, and it should be the initial treatment of choice for these patients.

PMID- 12514385
TI  - Quality of life, functional outcome, and costs of early glottic cancer.
AB  - OBJECTIVE: To analyze quality of life, functional outcome, and hidden costs by
      primary treatment with surgery or radiation therapy in patients with early
      glottic cancer. STUDY DESIGN: Retrospective study in a tertiary care facility.
      METHODS: A group of 101 patients with carcinoma in situ and T1 invasive squamous
      cell carcinoma treated primarily with either surgery or radiation, between
      January 1990 and December 2000, were identified from searching our tumor
      registry. Patients completed two previously validated questionnaires and one
      local questionnaire. Statistical significance was assessed with the rank sum
      test, chi2 test, or Fisher's Exact test. RESULTS: Questionnaires were completed
      in 59% (44 of 74) of the surgical cohort and 41% (11 of 27) of the radiation
      therapy cohort. The primary surgical treatments were endoscopic excision (86%),
      hemilaryngectomy (12%), and total laryngectomy (1%). Patient-reported problems
      with swallowing, chewing, speech, taste, saliva, pain, activity, recreation, and
      appearance showed no difference between the endoscopic excision or radiation
      therapy cohorts. Comparing endoscopic excision versus radiation therapy,
      respectively, median number of treatments (2 vs. 35), total median travel
      distance (150 vs. 660 miles), total median travel time (180 vs. 1440 min), and
      total median number of hours of work missed (76 vs. 24) all differed
      significantly (P <.01). CONCLUSIONS: Almost all patients with early glottic
      cancer, whether treated with surgery or radiation therapy, reported excellent
      quality of life outcomes and functional results. In addition to actual costs, the
      hidden costs for radiation therapy versus endoscopic excision were all greater in
      terms of total number of hours of work missed, total travel time, and total
      travel distance.

PMID- 12514386
TI  - Predictive value of serum thyroglobulin after surgery for thyroid carcinoma.
AB  - OBJECTIVE: To determine the relationship between stimulated serum thyroglobulin
      levels (taken 3 months after total thyroidectomy) and tumor stage and recurrence
      in patients with well-differentiated thyroid carcinoma. STUDY DESIGN:
      Retrospective chart review in a tertiary care institution. METHODS: Two hundred
      thirteen consecutive patients with well differentiated thyroid carcinoma treated
      between 1983 and 1998 were identified. Data were collected on clinicopathological
      variables, stimulated serum thyroglobulin levels obtained 3 months after total
      thyroidectomy prior to 131I therapy and recurrence. RESULTS: A high postoperative
      thyroglobulin level was significantly associated with advanced-stage disease at
      presentation (P =.005, Kruskall-Wallis) but not with any of the other
      clinicopathological variables. Patients with a thyroglobulin level greater than
      20 pmol/L had a significantly increased risk of disease recurrence on univariate
      analysis (n = 213 [P =.0001, log rank test]), and in the Cox proportional-hazards
      model, both advanced tumor stage (P =.001, relative hazard, 3.4 [95% confidence
      interval [CI]: 2.4-4.9]) and a thyroglobulin level greater than 20 pmol/L (P
      =.001, relative hazard, 5.1 [95% CI: 2.0-13.1]) were significant predictors of
      recurrence. No other variables significantly altered the hazards model.
      CONCLUSIONS: Advanced tumor stage at diagnosis and a stimulated thyroglobulin
      level greater than 20 pmol/L taken 3 months after total thyroidectomy were
      independent predictors of disease recurrence. Patients with a thyroglobulin level
      greater than 20 pmol/L are at increased risk of recurrence and may be candidates
      for more intensive follow-up or additional treatment.

PMID- 12514387
TI  - Intraparotid facial nerve neurofibromas.
AB  - OBJECTIVES: To provide an awareness of intraparotid facial nerve neurofibroma as
      a cause of parotid masses and to describe their characteristics and management
      considerations. STUDY DESIGN: Case report with literature review. METHODS: The
      medical records of three patients with intraparotid facial nerve neurofibromas
      are reviewed, and data concerning the patient's presentations, treatment, and
      disease course are presented with a review of the world's literature on
      intraparotid facial nerve neurofibromas. CONCLUSIONS: Tumors arising from the
      extratemporal course of the facial nerve are quite rare. The tumors arise from
      Schwann cells and include the schwannoma and the neurofibroma. The overwhelming
      benign nature of these lesions necessitates a conservative course of treatment.
      Histological diagnosis should be followed by a limited tumor excision with
      emphasis on retaining normal facial nerve function. Malignant lesions require
      wide excision with facial nerve grafting or facial nerve reanimation.

PMID- 12514388
TI  - Effect of chronic and short-term erythropoietin treatment on random flap survival
      in rats: an experimental study.
AB  - OBJECTIVE: The use of perioperative erythropoietin (EPO) therapy is gaining
      popularity to avoid blood transfusion and correct anemia in head and neck cancer
      surgery. The purpose of the study was to determine the effect of various doses
      and durations of EPO treatment on random flap survival. STUDY DESIGN: A McFarlane
      type random and musculocutaneous (3 x 10 cm) flap were elevated on the dorsum of
      each rat. METHODS: Eighty-four male Albino rats were randomly assigned into seven
      groups (2 animals in each group): group I, control animals receiving placebo;
      group II, chronic EPO injections (50 U/kg); group III, chronic EPO injections
      (100 mg/kg); group IV, chronic EPO injections (150 mg/kg); group V, short-term
      EPO injections (50 mg/kg); group VI, short-term EPO injections (100 mg/kg); and
      group VII, short-term EPO injections (150 mg/kg). Rats in groups II to IV began
      to receive EPO 3 weeks (thrice weekly) before the construction of flaps, and rats
      in groups V to VII received EPO after flap elevation for 1 week (thrice)
      subcutaneously. Following 7 days of recovery, the area of flap survival was
      measured. Hematocrit and systolic blood pressure were followed weekly in all
      groups. RESULTS: Erythropoietin increased the hematocrit levels and systolic
      blood pressure in all groups, but significant increases were noted only in the
      long-term treatment groups. There was a significant increase in distal necrosis
      of random skin flaps after long-term EPO treatment (P <.05). However, short-term
      low and therapeutic doses of EPO improved flap survival significantly (P <.05).
      CONCLUSIONS: Long-term EPO treatment might have impaired flap survival because of
      direct or prostaglandin-mediated vasoconstriction, endothelin-induced
      hypertension, increased peripheral vascular resistance, hyperviscosity, and
      increased thrombosis. However, EPO might have enhanced flap survival because of
      its antioxidant effect and modulation of nitric oxide levels. Effects of EPO are
      controversial, and further research is necessary to delineate the dose and
      duration relationship and the exact mechanism of action on flap viability.

PMID- 12514389
TI  - In vitro tissue engineering to generate a human-sized auricle and nasal tip.
AB  - OBJECTIVES/HYPOTHESIS: Tissue engineering has successfully generated cartilage in
      a xenograft and an autograft model. However, challenges remain with both of these
      in vivo techniques before clinical application can be realized. We hypothesized
      that a human-sized cartilaginous structure could be generated completely in vitro
      as a complementary or an alternative technique. METHODS: Scaffolds were created
      in the shape of five full-sized human auricles and five nasal tip cartilaginous
      skeletons. Bovine shoulder chondrocytes at a concentration of 50 million cells/mL
      were seeded onto the scaffolds and were grown for 12 weeks in vitro. Two of the
      auricular scaffolds had internal support provided by soft acrylic sheets and were
      later implanted into nude rats. RESULTS: All of the scaffolds maintained shape
      and size through 12 weeks of in vitro culture. On gross examination the scaffolds
      were progressively replaced by cartilage, which was confirmed by histological and
      biochemical analysis. The auricular scaffolds with the acrylic internal support
      had the most natural rigidity, which was observed by gentle palpation. The nasal
      scaffolds maintained excellent definition even without internal support.
      CONCLUSION: An adult human-sized auricle and nasal tip cartilaginous structure
      can be grown entirely in vitro using principles of tissue engineering.

PMID- 12514390
TI  - A novel technique for peripheral nerve repair.
AB  - OBJECTIVE: To evaluate a novel technique for the repair of neural deficits using
      a single fascicle to bridge an injury in the rat sciatic nerve. STUDY DESIGN:
      Twenty-four male Lewis rats were divided into four groups as follows: group 1
      (control group), 1.5-cm deficit without repair; group 2, conventional epineural
      repair with autografts (100% diameter); group 3, nerve repair with large single
      autograft fascicle (50% diameter); and group 4, nerve repair with small single
      autograft fascicle (25% diameter). METHODS: Nerve regeneration was evaluated at
      3, 6, and 12 weeks by somatosensory evoked potential (SSEP) evaluation and
      standardized pin-prick and toe-spread tests. Nerve samples were harvested at 12
      weeks and stained with toluidine blue to assess the total number of myelinated
      axons, axon area, and myelin sheath thickness. RESULTS: In group I, the pin-prick
      and toe-spread tests showed no response at 3, 6, and 12 weeks. Rats in groups 3
      and 4 demonstrated significantly better pin-prick test results and a trend toward
      better toe-spread test responses compared with conventional-repair animals. The
      SSEP evaluations displayed nondiagnostic waves in rats in group 1 rats. There was
      no evidence that the other surgery groups differed significantly in median SSEP
      latencies. Histological evaluation revealed fibrosis in rats in group 1 rats and
      a significantly higher median number of axons and myelin thickness in the small
      single fascicle (1296 axons and 4.22 microm, respectively) and large fascicle
      (2682 axons and 4.62 microm, respectively) groups compared with the conventional
      autograft group (630 axons and 2.93 microm, respectively). The small fascicle
      group had a significantly greater mean axon area (58.59 micro m2) than the large
      fascicle (29.66 micro m2) and conventional autograft (25.35 micro m2) groups.
      CONCLUSIONS: Peripheral nerve repair using a single fascicle graft resulted in
      better functional recovery and morphometric outcome without a significant
      difference in electrophysiological status compared with conventional nerve
      repair. This technique may provide expanded sources of nerve autografts and
      alleviate the morbidity of harvesting peripheral nerves from multiple sites for
      individuals with extensive peripheral nerve injuries.

PMID- 12514391
TI  - Facial fractures and concomitant injuries in trauma patients.
AB  - OBJECTIVES/HYPOTHESIS: Maxillofacial fractures often occur with serious
      concomitant injury in trauma patients, and knowledge of the type and severity of
      associated injuries can assist in rapid assessment and treatment. The objective
      was to identify the most commonly occurring injuries associated with facial
      fractures in severely injured trauma patients. STUDY DESIGN: Review of medical
      records. METHODS: A retrospective review was made of 151 patients with facial
      fractures presenting to a level-one trauma center over a 4-year span. All
      patients had an injury severity score of 12 or greater. Chart data recorded
      included demographics, etiology, presentation, facial fracture site, concomitant
      injury, imaging studies, hospital stay and course, interventions, and outcome.
      RESULTS: The most common cause or origin of facial fracture was assault (41%),
      followed by motor vehicle accident (26.5%). Orbital fracture was the most common
      overall facial fracture (24.2%), with nasal fractures being the most common
      isolated fracture (23.2%). Cerebral hematoma occurred in 43.7% of patients, with
      subdural hematoma being the most frequent. Pulmonary injury was the second most
      commonly associated injury (31.1%) with lung contusion being the most frequent.
      Seventy-two patients (42%) required intubation, and 22 (14.8%) required
      tracheostomy during their hospital stay. The hospital complication rate was 50.3%
      and included primarily pulmonary complications, septicemia, renal failure, and
      severe anemia. Thirteen patients died during their hospital stay; 11 of them died
      of neurologic injuries, 1 of pulmonary failure, and 1 of overwhelming sepsis.
      CONCLUSIONS: Cerebral and pulmonary injuries are often associated with
      maxillofacial fractures in severely injured trauma patients. Knowledge of these
      associated injuries provides useful strategies for patient care and prevention of
      further complications. A multidisciplinary and coordinated approach is important
      for optimum stabilization and ongoing treatment of patients with facial
      fractures.

PMID- 12514392
TI  - The treatment of drooling by ultrasound-guided intraglandular injections of
      botulinum toxin type A into the salivary glands.
AB  - OBJECTIVE: The aim of the study was to present the background, procedure, and
      technique of bilateral ultrasound-guided, single-dose injections of botulinum
      toxin type A (BTX) into the salivary glands in patients with severe drooling.
      STUDY DESIGN: Clinical trial. METHODS: Initially, an in vitro study was performed
      to determine the volume of the dilution of BTX required for optimal spreading and
      to gain insight in the spreading pattern of the fluid in the submandibular gland.
      Subsequently, patients with severe drooling were included in a clinical study.
      Salivary flow was measured under standardized conditions, and BTX was injected
      into the submandibular glands with the patient under general anesthesia and with
      ultrasound guidance as an outpatient procedure or during a short stay at the
      daytime care unit. RESULTS: BTX for each gland should be diluted in a volume of 1
      to 1.5 mL saline to achieve adequate spreading within the gland and to diminish
      the risk of diffusion into surrounding structures. With ultrasound guidance,
      separate structures surrounding the glands and structures within the glandular
      parenchyma are well recognized and injection errors can be avoided. CONCLUSIONS:
      With the procedure described, it is possible to accurately inject BTX directly
      into the glandular parenchyma and to visualize spreading of the fluid in the
      glandular parenchyma. It is found to be a safe method that guarantees an optimal
      clinical effect and avoids potentially harmful side effects. We recommend
      ultrasound guidance if injections of BTX into the salivary glands are considered.

PMID- 12514393
TI  - Delayed optic nerve decompression for indirect optic nerve injury.
AB  - OBJECTIVE: To test the efficacy of delayed optic nerve decompression in traumatic
      optic nerve injury. STUDY DESIGN: Critical analysis of Proforma-based,
      prospectively accrued data of all cases with injury to surgery interval of
      greater than 2 weeks. METHODS: Thirty-five cases with a median injury to surgery
      interval of 56 days (range, 16-374 d). Surgical decompression was undertaken only
      in cases that continued to have poor vision after treatment with steroids in
      conventional doses (1 mg/kg prednisolone). Pre- and postoperative visual acuity
      measurements were converted to the logMAR scale of visual acuity and the
      percentage of visual improvement was calculated. RESULTS: Surgery was universally
      unrewarding in all 9 cases with persistent and complete blindness of greater than
      2 weeks and no response to steroid therapy. Of the cases with some residual
      vision, 20 of 26 cases improved (mean percentage improvement, 41.0 +/- 5.7%).
      Cases were categorized on the basis of the injury to surgery interval into groups
      of 2 weeks to 2 months, 2 months to 4 months, and greater than 4 months. No
      significant difference was demonstrated in the probability or quantum of
      improvement in these groups (P =.97). CONCLUSIONS: Optic nerve decompression
      remains useful as a salvage procedure for conventional dose steroid failed cases
      of traumatic optic neuropathy. In cases that are not completely blind, vision can
      be improved even when surgery is undertaken a few months after the injury.

PMID- 12514394
TI  - The pathogenesis of nasal polyposis by immunoglobulin E and interleukin-5 is
      completed by transforming growth factor-beta1.
AB  - OBJECTIVES/HYPOTHESIS: Nasal polyps are benign mucosal protrusions into the nasal
      cavity of multifactorial origin and are characterized by chronic mucosal
      inflammation. The suggested multifactorial pathological mechanisms comprise
      several factors including cytokines and immunoglobulin E (IgE). The study was
      designed to examine the suggested roles of IgE, interleukin-5 (IL-5), and
      transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of nasal
      polyposis. METHODS: Nasal polyps (n = 34) and healthy nasal mucosa samples (n =
      9) were taken during routine endonasal surgeries. Immunoglobulin E (n = 13), IL-5
      (n = 22), and TGF-beta1 (n = 27) concentrations were measured with enzyme-linked
      immunosorbent assay technique in homogenized polyp tissue and in control mucosa.
      Atopic and nonatopic groups were selected and compared. Histomorphological
      examination and immunohistochemical analysis to detect IL-5 and TGF-beta1 were
      performed in five specimens. RESULTS: The level of tissue-bound IgE was
      significantly higher in polyps compared with control specimens and in atopic
      compared with nonatopic polyps, but between nonatopic polyps and control
      specimens the difference was not significant. However, significant correlation
      was found between tissue and serum IgE in the complete polyp (P =.001) and atopic
      polyps group (P =.05). Tissue IL-5 concentration was significantly higher in
      polyps compared with control specimens, in which it was below the limit (15
      pg/mL), and there was no difference between atopic and nonatopic polyps. In
      atopic polyps there was significant correlation between tissue IgE and IL-5.
      Transforming growth factor-beta1 concentration proved to be significantly higher
      in control mucosa than in polyps, with no difference between atopic and nonatopic
      polyps. Immunohistochemical analysis revealed numerous IL-5-positive eosinophil
      cells and TGF-beta1 positivity in the lamina propria of polyp samples, but none
      in control specimens. CONCLUSIONS: High tissue TGF-beta1 quantity in healthy
      nasal mucosa without its active form on the cell surface and its low quantity in
      polyps may reflect its essential role in the inhibitory mechanisms of nasal
      polyposis. Interleukin-5 plays a key role in the eosinophil recruitment and
      activation, and both atopic and nonatopic pathways might activate this process.
      The main sources of IL-5 and TGF-beta1 are the eosinophils and macrophages.
      Immediate hypersensitivity, besides other mechanisms, might be related to atopic
      polyps, but the involvement of other, local allergic mechanisms in IgE production
      of nonatopic polyp tissue cannot be excluded.

PMID- 12514395
TI  - The accuracy of computed tomography in the diagnosis of chronic rhinosinusitis.
AB  - OBJECTIVE: To determine the sensitivity, specificity, and diagnostic accuracy of
      paranasal sinus computed tomography (CT) in the diagnosis of chronic
      rhinosinusitis (CRS). STUDY DESIGN: Prospective dual cohort study. METHODS: One
      hundred seventy-one consecutive patients undergoing endoscopic sinus surgery for
      CRS were evaluated with CT and staged according to the Lund system.
      Histopathological findings from sinus specimens were reviewed and graded. A
      second contemporaneous control group of 130 patients undergoing CT of the sinus
      regions for other reasons but without a diagnosis of CRS was also staged.
      Sensitivity, specificity, and the receiver-operator characteristic were
      determined for the sinus CT in the diagnosis of CRS. Positive and negative
      predictive values were also computed. RESULTS: In the disease-positive group of
      patients with CRS, the mean Lund score was 9.8 (95% confidence interval, 9.0
      10.6). The mean inflammatory grade on histopathological study was 2.3 (range, 0
      4). For the control group (without disease), the mean Lund score was 4.3 (95%
      confidence interval, 3.5-5.0). The AUC for the receiver-operator characteristic
      was 0.802 (P <.001). Selecting a Lund score cut-off value of greater than 2 as
      abnormal, the sinus CT exhibited sensitivity and specificity of 94% and 41%,
      respectively. Increasing the cut-off value to 4 changed the sensitivity and
      specificity to 85% and 59%, respectively. CONCLUSIONS: The paranasal sinus CT
      scan exhibits good sensitivity and above-average specificity for the diagnosis of
      CRS. When added to the history and physical findings, CT may add to the
      diagnostic accuracy of CRS.

PMID- 12514396
TI  - Bipolar radiofrequency-induced thermotherapy of turbinate hypertrophy: pilot
      study and 20 months' follow-up.
AB  - OBJECTIVES/HYPOTHESIS: The present report is a pilot clinical study about a new
      bipolar ablation technique for the treatment of turbinate hypertrophy, which
      offers an alternative to conventional methods. STUDY DESIGN: Prospective,
      clinical. METHODS: From August 1999 to March 2000, a new bipolar radiofrequency
      system with acoustic feedback control was submucosally applied for the treatment
      of 38 patients with nasal airway obstruction of vasomotor (n = 31) or allergic (n
      = 7) genesis. The therapy was made ambulatory with surface anesthesia. Data were
      collected by questionnaire and rhinomanometry preoperatively and 2 and 20 months
      postoperatively. RESULTS: Nearly all patients reported an improvement of their
      nasal breathing, with 68% of them reporting a full and 29% a partial recovery. No
      significant differences were reported with regard to the response of the allergic
      versus the vasomotor rhinitis. On average, a definite benefit was observed after
      2 weeks. Side effects, such as bleeding, synechia, or atrophic changes of the
      mucosa, which would have to be treated, were not observed. CONCLUSION: The new
      bipolar radiofrequency thermotherapy presents an efficient option for the
      treatment of turbinate hypertrophy, which meets the requirements for an
      outpatient treatment.

PMID- 12514397
TI  - Transnasal endoscopic closure of cerebrospinal fluid leaks.
AB  - OBJECTIVES/HYPOTHESIS: To demonstrate an effective method for transnasal
      endoscopic closure of anterior skull base fistulas that does not involve lumbar
      drains or fat packing. STUDY DESIGN: Retrospective. METHODS: We reviewed the
      charts of 36 patients who had 37 anterior skull base defects that were repaired
      endoscopically between 1993 and 2001. RESULTS: Thirty-three defects were
      successfully closed on the first attempt. Three were successfully closed on the
      second attempt. One large defect was repaired by neurosurgery after a failed
      endoscopic attempt. Our results are similar to those of other published series.
      CONCLUSION: Our method is effective and does not require adjuvant procedures or
      prolonged hospital stays.

PMID- 12514398
TI  - Microdebrider versus CO2 laser removal of recurrent respiratory papillomas: a
      prospective analysis.
AB  - OBJECTIVE: To compare postoperative patient discomfort, voice quality, and
      procedure time and cost for removal of recurrent respiratory papillomas using the
      microdebrider versus the CO2 laser. STUDY DESIGN: A randomized prospective study
      comparing children undergoing excision of recurrent respiratory papillomas by CO2
      laser versus excision by microdebrider. METHODS: For the 6-month study, patients
      for whom removal of recurrent respiratory papillomas was indicated were randomly
      assigned by birth year to microdebrider or CO2 laser therapy. Disease severity
      was scored as the sum of ratings of 1+ (minimal), 2+ (moderate), or 3+ (severe)
      for involvement of 27 areas of the aerodigestive tract by direct
      microlaryngoscopy immediately before treatment. Parents scored patient discomfort
      and improvement in voice quality 24 hours after surgery, using a 5-point (0 = no
      pain; 4 = worst pain) and a 10-point (1 = minimal change; 10 = significant
      improvement) scale, respectively. RESULTS: Nineteen patients ranging in age from
      2.5 to 20 years underwent 32 procedures in all. Groups did not differ
      significantly in age, sex, or severity of disease. For disease of equivalent
      severity, microdebrider treatment was associated with equivalent 24-hour
      postoperative pain scores, greater improvement in voice quality, shorter
      procedure times, and lower overall procedure cost. CONCLUSIONS: Immediate
      postoperative results indicate that the microdebrider may be as safe as and, at
      some institutions, might be more cost-effective than the CO2 laser for removal of
      recurrent respiratory papillomas.

PMID- 12514399
TI  - Roles of hepatocyte growth factor and transforming growth factor beta1 in
      production of extracellular matrix by canine vocal fold fibroblasts.
AB  - BACKGROUND/OBJECTIVES: When the lamina propria of the vocal fold is replaced by
      fibrosis after wound healing, it is difficult to restore an appropriate
      viscoelasticity of the vocal fold. To treat fibrotic scarring, material that
      reduces collagen deposition and increases soft amorphous substances, such as
      hyaluronic acid, is required. The potential use of hepatocyte growth factor (HGF)
      is intriguing. In this study, the authors examined canine vocal fold fibroblasts
      to determine how HGF contributes to the production of extracellular matrix. More
      specifically, the authors describe how the productions of hyaluronic acid,
      collagen type I, and fibronectin are associated with administration of HGF and
      transforming growth factor beta1. STUDY DESIGN: In vitro. METHODS: Fibroblasts
      were collected from the lamina propria of the vocal folds of five Beagles and
      were cultured with and without HGF or transforming growth factor beta1. The
      productions of hyaluronic acid, collagen type I, and fibronectin in supernatants
      culture were examined using ELISA. RESULTS: Hepatocyte growth factor stimulated
      hyaluronic acid production, reduced collagen type I production, and did not
      affect fibronectin production, while transforming growth factor beta1 stimulated
      the productions of all components. CONCLUSIONS: Collagen type I appears to be a
      major contributor in creation of fibrosis, and excessive fibronectin may stiffen
      the tissue. Since HGF reduced collagen type I production from fibroblasts and
      increased hyaluronic acid, HGF is considered to have therapeutic potential in
      prevention and treatment of the fibrosis of the vocal fold.

PMID- 12514400
TI  - Nontuberculous mycobacterial cervical adenitis: a ten-year retrospective review.
AB  - OBJECTIVE: To review the authors' institutional experience with nontuberculous
      mycobacterial cervical adenitis in children over a 10-year period. STUDY DESIGN:
      Retrospective chart review. METHODS: The case histories of 79 children with
      nontuberculous mycobacterial lymphadenitis who presented to a large tertiary care
      referral center from 1989 to 1999 were retrospectively analyzed, and the
      demographics, clinical presentation, methods of diagnosis, and types of surgical
      intervention they underwent were reported. RESULTS: The mean age at presentation
      was 3.6 years. The male-to-female ratio was 1:2, and the frequency of
      presentation was highest in the winter and spring months. The diagnosis was not
      immediately apparent to most primary health care physicians because there was a
      delay between the appearance of the lump and referral for treatment, which was in
      excess of 8 weeks. Involved nodes were mainly treated surgically. The recurrence
      rate of complete surgical resection was less than 1%. CONCLUSION: The study
      highlights the fact that a high index of clinical suspicion is needed to make an
      early diagnosis of nontuberculous mycobacterial lymphadenitis and lends further
      weight to the already existing evidence that surgical excision remains the
      mainstay of successful treatment for lymphadenitis caused by nontuberculous
      mycobacteria.

PMID- 12514401
TI  - Esthesioneuroblastoma: the Northwestern University experience.
AB  - OBJECTIVE: To review our experience with esthesioneuroblastoma, a rare malignancy
      of the head and neck. STUDY DESIGN: Retrospective review of Tumor Registry data.
      METHODS: We performed a computerized search of the Northwestern Memorial Hospital
      Tumor Registry database from 1981 to 2000. RESULTS: Sixteen patients with
      esthesioneuroblastoma were identified and analyzed. Their mean age was 42 years.
      Eleven of 16 patients (69%) had Kadish stage C; 8 patients (50%) had brain
      involvement at presentation. Craniofacial resection was performed in 13 patients
      (81%). Fourteen patients received either preoperative or postoperative therapy;
      radiation therapy was employed in 11 cases and chemotherapy in 4. The actuarial 5
      year survival was 60%, and the actuarial 5-year disease-free survival was 33%,
      with a median follow-up of 4.3 years. Recurrences occurred at a median time of 11
      months after diagnosis (2.5 mo-18 y). The first site of failure was locoregional
      alone in 10 of 12 patients who progressed, and in 6 patients involved the brain
      or the meninges. Two patients were successfully salvaged. Patients with high
      grade tumors had a trend toward work survival. CONCLUSIONS: Esthesioneuroblastoma
      is a rare tumor that is potentially curable by surgical resection and radiation
      therapy. However, the rate of local failure is high, and late recurrences are not
      uncommon. The role of chemotherapy warrants further investigation.

PMID- 12514402
TI  - Association between tobacco use and metastatic neck disease.
AB  - OBJECTIVES/HYPOTHESIS: Tobacco has multiple effects on connective tissues that
      might affect tumor behavior. This study examined the association between tobacco
      use and tumor behavior (lymphatic metastasis and extracapsular spread) in head
      and neck cancers. STUDY DESIGN: Chart audit. METHODS: Medical records of patients
      from the Department of Otolaryngology, University of Pittsburgh Medical Center
      (Pittsburgh, PA) with oral cavity, pharyngeal, and laryngeal cancers who
      underwent neck dissection were reviewed focusing on their tobacco use habits, as
      well as the clinical and pathological criteria of primary tumors and cervical
      lymph nodes. Univariate and multivariate analyses were performed to study the
      significance between pathological and tobacco use variables. RESULTS: The study
      included 171 patients. Both univariate and multivariate analyses revealed
      significant associations between tobacco use and pathological findings. Cervical
      metastasis was observed in 100% of tobacco users and 54% of nonusers (P <.0001).
      Extracapsular spread was observed in 100% of tobacco users and 19% of nonusers (P
      <.0001). Tobacco use was independently associated with pathological nodal stage
      in multivariate analysis. Former users and light users of tobacco were not at
      reduced risk of cervical metastasis or extracapsular spread. CONCLUSIONS: The
      study demonstrates that tobacco use is a possible risk factor for cervical
      metastasis and extracapsular spread, which may be helpful information in planning
      therapy for patients with clinically staged node-negative necks.

PMID- 12514404
TI  - In-office tracheoesophageal puncture using transnasal esophagoscopy.

PMID- 12514403
TI  - p53 and cyclin D1 as prognostic factors in squamous cell carcinoma of the larynx.
AB  - OBJECTIVES/HYPOTHESIS: Proteins p53 and cyclin D1 play a crucial role in cell
      cycle control. Protein p53 mutations are one of the most common genetic
      alterations in human cancer, and cyclin D1 gene amplification has been found to
      be associated with poor prognosis in different types of tumors. Functional
      alterations of these proteins may play an important role both in the
      carcinogenesis of squamous carcinomas of the head and neck and in the clinical
      evolution of these tumors. The objective of the present study was to evaluate
      whether the presence of p53 and/or cyclin D1 proteins (detected by
      immunohistochemical analysis) could serve as relevant variables for the
      assessment of the prognosis of laryngeal squamous cell carcinoma. STUDY DESIGN:
      Retrospective multicentric study. METHODS: Paraffin-embedded biopsy specimens
      from 62 human epidermoid laryngeal carcinomas were randomly selected. The
      expression of p53 and cyclin D1 was examined by means of immunohistochemical
      analysis with a view to evaluating whether there is a correlation between the
      aberrant expression of these proteins and disease prognosis. RESULTS: In the
      sample, the presence of immunohistochemically detectable p53 is associated with
      shorter survival and disease-free intervals, as shown in Kaplan-Meier survival
      curve analysis. Indeed, multivariate statistical analysis revealed that the
      accumulation of p53 is an independent prognostic factor, which is associated with
      shorter survival. This association was not evident in the case of cyclin D1.
      CONCLUSION: A more precise prognosis of patients with laryngeal epidermoid
      carcinomas could be achieved by taking into account the presence of p53 (as
      assayed by immunohistochemical analysis) in biopsy tissue

PMID- 12514405
TI  - Surgical closure of the larynx for intractable aspiration: surgical technique
      using closure of the posterior glottis.

PMID- 12514406
TI  - Occult carbon monoxide poisoning in ENT practice: a word of caution.

PMID- 12514407
TI  - JAIDS at 15: meeting the challenge. Editorial.

PMID- 12514408
TI  - The potential public health and community impacts of safer injecting facilities:
      evidence from a cohort of injection drug users.
AB  - BACKGROUND: Although medically supervised safer injecting facilities (SIFs)
      remain untested in North America, their implementation is currently being
      debated. Reluctance of health policy makers to initiate a pilot study of SIFs may
      in part be hindered by outstanding questions regarding the potential community
      and public health impact of the intervention. Specifically, it is presently
      unknown if those at greatest risk of overdose and HIV transmission or those
      responsible for community impact of injection drug use will be willing to attend.
      METHODS: The current study was conducted to evaluate the proportion of injection
      drug users (IDU) willing to attend medically supervised SIFs, if they were
      available, among participants enrolled in the Vancouver Injection Drug User Study
      (VIDUS). The authors also evaluated factors associated with willingness to use a
      SIF using univariate and logistic regression analyses. Participants who were
      followed from June 2001 to June 2002 were eligible for the present analyses.
      RESULTS: Overall, 587 active IDU responded to a questionnaire during the study
      period. Among respondents, 215 (36.6%) expressed willingness to attend a SIF.
      Variables that were independently associated with willingness to attend a SIF in
      multivariate analyses included having difficulty accessing sterile syringes
      (adjusted odds ratio [AOR] = 2.07), requiring help injecting (AOR = 1.52),
      frequently injecting heroin (AOR = 1.81), sex trade work (AOR = 2.02), and
      injecting in public spaces (AOR = 2.00). CONCLUSIONS: Several variables that have
      recently been associated with overdose, syringe sharing, HIV and HCV incidence,
      and community impact of illicit drug use in this setting were associated with
      willingness to attend medically supervised SIFs. Although the impact of SIFs in
      North America can only be quantified by scientific evaluation, these data
      indicate a high potential for immediate community and public health benefits if
      SIFs were presently available.

PMID- 12514409
TI  - Comparison between env-specific T-cell epitopic responses in HIV-1-uninfected
      adults immunized with combination of ALVAC-HIV(vCP205) plus or minus rgp160MN/LAI
      2 and HIV-1-infected adults.
AB  - In this study, we investigated the CD4 T-helper response induced by ALVAC
      HIV(vCP205) +/- rgp160MN/LAI-2 using a series of 15 overlapping amino acid
      peptides spanning the entire gp160MN/LAI-2 antigen. CD4 Env-specific T-cell lines
      were established from three groups of HIV-1-negative HIV vaccine recipients:
      vCP205 + gp160MN/LAI-2, vCP205 only, and gp160MN/LAI-2 only. CD4 Env-specific T
      cell lines established from individuals who received the prime-boost vCP205 +
      rgp160MN/LAI-2 generated strong and broad T-helper responses scattered across the
      Env sequence, whereas Env-specific T-cell lines from individuals receiving the
      vCP205 vaccine alone generated reactivity to only a few peptides. CD4 -specific T
      cell lines were also established from HIV-1-infected individuals and demonstrated
      poor reactogenicity to Env peptides in both breadth and amplitude of response.
      These results highlight the complexity of major histocompatibility complex class
      II presentation and CD4 antigen-specific reactivity, emphasizing the need to
      better understand these crucial T-helper cell responses in the setting of HIV
      infection and HIV vaccine development.

PMID- 12514410
TI  - Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging,
      safety, and efficacy comparative trial of atazanavir at three doses in
      combination with didanosine and stavudine in antiretroviral-naive subjects.
AB  - Three dose levels of the protease inhibitor (PI) atazanavir (200, 400, and 500 mg
      once daily) were compared with nelfinavir (750 mg three times daily) when given
      both as monotherapy and in combination with didanosine and stavudine in 420
      antiretroviral-naive subjects infected with HIV-1. Subjects received monotherapy
      for 2 weeks, followed by combination therapy for 46 weeks. After 48 weeks, mean
      change from baseline in HIV RNA (-2.57 to -2.33 log 10 copies/mL), the proportion
      of subjects with HIV RNA <400 copies/mL (56%-64%) and <50 copies/mL (28%-42%),
      and mean increases in CD4 cell count (185-221 cells/mm 3) were comparable across
      treatment groups. Diarrhea was two to three times more common in the nelfinavir
      group (61% of subjects) than in the atazanavir groups (23%-30% of subjects,
      <.0001 versus nelfinavir), and jaundice occurred only in atazanavir-treated
      subjects (6%, 6%, and 12% in the 200-, 400-, and 500-mg groups, respectively) (
      <.03 for all atazanavir regimens vs. nelfinavir). Mean percent change from
      baseline in fasting low-density lipoprotein (LDL) cholesterol was significantly
      less in the atazanavir groups (-7% to 4%) than in the nelfinavir group (31%) (
      <.0001). In conclusion, once-daily atazanavir is a potent, safe, and well
      tolerated PI that rapidly and durably suppresses HIV RNA and durably increases
      CD4 cell count in antiretroviral-naive subjects. Through 48 weeks, atazanavir was
      not associated with clinically relevant increases in total cholesterol, fasting
      LDL cholesterol, or fasting triglycerides. In comparison, nelfinavir was
      associated with prompt, marked, and sustained elevations in these parameters of a
      magnitude that suggests they are clinically relevant.

PMID- 12514411
TI  - The clinical spectrum of hepatitis C virus in HIV coinfection.
AB  - The biochemical, virologic, and histologic spectrum of hepatitis C virus (HCV) in
      66 consecutive patients with HIV-HCV coinfection and 119 HCV controls was
      compared: 86% of coinfected patients had CD4 counts >200 cells/mm3, 51% had a
      normal alanine aminotransferase (ALT) value, the mean HCV RNA titer was 5.7 log
      IU/mL, 92% of coinfected patients were of genotype 1, and the mean histologic
      activity index was 6.86 with advanced fibrosis in 32% of patients. The
      biochemical, virologic, and histologic findings of HCV in coinfected patients
      were similar to those observed in HCV controls. For both groups of patients, no
      clinical, biochemical, or virologic factors could reliably identify patients with
      advanced fibrosis or cirrhosis, underscoring the importance of liver biopsy in
      the evaluation of these patients. The spectrum of liver disease in coinfection
      includes a significant proportion of patients with normal ALT values, and
      excluding these patients from previous studies has led to an overestimation of
      HCV disease severity.

PMID- 12514412
TI  - Health-related quality of life after 1 year of highly active antiretroviral
      therapy.
AB  - OBJECTIVE: We investigated the impact of the first year of highly active
      antiretroviral therapy (HAART) on health-related quality of life (HRQL). METHODS:
      Medical data for patients in the French APROCO cohort were collected at
      enrollment (M0) and month 12 (M12). A self-administered questionnaire gathered
      information about HRQL (Medical Outcome Study 36-Item Short Form Health Survey)
      and toxicity-related symptoms. Using the twenty-fifth percentile of HRQL scales
      in the French population as a threshold, patients with normal values in at least
      three mental and three physical scales were considered to have a "normal HRQL."
      RESULTS. Of the 1053 patients followed through M12, HRQL data at M0 and M12 were
      available for 654. Among the 233 patients with a normal baseline HRQL, 63 (27.0%)
      experienced a deterioration of HRQL at M12. Among the 421 patients with a low
      baseline HRQL, 121 achieved a normal HRQL at M12. Logistic regression showed that
      factors independently associated with a normal HRQL at M12 were normal baseline
      HRQL, baseline CD4 count <500 cells/mm, time since HIV diagnosis <8 years,
      undetectable HIV-RNA at M12, and lower number of self-reported symptoms at M12.
      CONCLUSION: An assessment of HRQL should be integrated to efficacy outcomes to
      evaluate and compare long-term strategies properly and to optimize the durability
      of response to antiretroviral therapy.

PMID- 12514413
TI  - Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory
      HIV-1-infected patients.
AB  - To identify clinical factors associated with the incidence of HIV-1-associated
      lipoatrophy, HIV-1-infected patients in the HIV Outpatient Study (HOPS) were
      prospectively evaluated for clinical signs of lipoatrophy at two visits about 21
      months apart. Development of lipoatrophy was analyzed in stratified and
      multivariate analyses for its relationship to immunologic, virologic, clinical,
      and drug treatment information for each patient. Of 337 patients with no
      lipoatrophy at Survey 1, 44 (13.1%) developed moderate or severe lipoatrophy
      between the two surveys. In multivariate analyses, significant risk factors for
      incident lipoatrophy were white race (OR = 5.2; 95% CI: 1.9-17.1; =.003), CD4 T
      lymphocyte count at Survey 2 less than 100 cells/mm3 (OR = 4.2; 95% CI: 1.3-13.1;
      =.013), and body mass index (BMI) less than 24 kg/m2 (OR = 2.4; 95% CI: 1.1-5.4;
      =.024). Analyses that controlled for the severity of HIV illness demonstrated no
      significant association with use of or time on any antiretroviral agent or class
      of agents and the development of lipoatrophy. Some host factors and factors
      associated with previous or current severity of HIV infection, especially CD4 T
      lymphocyte cell count, appeared to have the strongest association with incidence
      of lipoatrophy.

PMID- 12514414
TI  - Limited evolution of HIV antiretroviral drug resistance-associated mutations
      during the performance of drug resistance testing.
AB  - We investigated the evolution of HIV reverse transcriptase (RT)- and protease
      associated antiretroviral (ARV) drug resistance mutations during the time taken
      to perform genotypic drug resistance testing. Thirty treatment-experienced
      patients who were adherent to therapy and who underwent genotypic drug resistance
      testing provided blood samples at randomization and when reviewing the test
      results (baseline). Patients remained on their existing therapy between
      randomization and baseline. The predominant HIV strains in 10 patients (33%)
      either lost and/or gained primary RT inhibitor (RTI)- or protease inhibitor (PI)
      associated resistance mutations during the testing period. Of the 9 patients with
      RT mutations, 2 lost, 5 gained, and 2 both lost and gained RTI resistance
      mutations. One patient gained a significant PI-associated resistance mutation on
      an existing PI-resistant background. The evolution that occurred in the RT may
      have altered the effectiveness of subsequent ARV therapy in some patients.
      Neither viral load at randomization, ARV drug class used at randomization, time
      between collection of blood samples, duration of current therapy, nor number of
      ARV drugs used influenced gain or loss of resistance mutations. There was a
      significant association between duration of previous ARV therapy and gain of RTI
      associated resistance mutations ( p =.02), however. In general, our results
      suggest that patients should continue current therapy until test results are
      available. A few patients would be expected to gain ARV drug-associated
      resistance mutations during this time, however.

PMID- 12514415
TI  - Increase in deaths caused by HIV infection due to changes in rules for selecting
      underlying cause of death.
AB  - With implementation of the (ICD-10), for U.S. vital statistics in 1999, the
      criteria for selecting HIV infection as the underlying cause of death were
      expanded. To estimate the effect of ICD-10 rules on the number of deaths
      attributed to HIV infection, we applied a simplified version of ICD-10 rules to
      data on causes of death from all U.S. death certificates for 1998 (previously
      classified by rules of the 9th revision of ICD [ICD-9]) and calculated the
      resulting increase in deaths for which HIV infection was selected as the
      underlying cause. Of the 17,186 deaths in 1998 with any mention of HIV infection
      on the death certificate, ICD-10 rules selected HIV infection as the underlying
      cause for 15,145, which was 1,719 (13%) more than the 13,426 for which it had
      been selected by ICD-9 rules. The proportional increase differed by demographic
      group, being less among non-Hispanic blacks (9%) and Hispanics (13%) than among
      non-Hispanic whites (18%). Thus, comparison of deaths attributed to HIV infection
      in 1999 or later with those in 1998 or earlier should take into account the
      changes in ICD rules for selecting the underlying cause of death.

PMID- 12514416
TI  - Effect of CCR5-delta32 heterozygosity on the risk of perinatal HIV-1 infection: a
      meta-analysis.
AB  - Several studies have investigated whether heterozygosity for a 32-basepair
      deletion in the CC chemokine receptor 5 gene (CCR5-Delta32 ) affects
      susceptibility to perinatal HIV-1 infection, but results have been inconclusive.
      We performed a meta-analysis of published data from 11 studies of HIV-1
      perinatally exposed children who were genotyped for the CCR5-Delta32
      polymorphism. The crude overall HIV-1 infection rates, by simple data pooling,
      were 20% (one of five) amongCCR5-Delta32 homozygote children, 39% (131 of 335)
      among CCR5-Delta32 heterozygote children, and 40% (1408 of 3526) among wild-type
      CCR5 homozygote children. Compared with wild-type homozygotes, the random effects
      risk ratio for heterozygotes was 1.04 (95% confidence interval [CI], 0.92-1.17)
      among all children (N = 3861) and 1.03 (95% CI, 0.90-1.17) among those of
      European descent (n = 2890). Results were similar when adjusted for the available
      data on the CCR2-641 polymorphism (n = 1542). The meta-analysis clarifies that
      perinatal infection is not significantly altered by heterozygosity for CCR5
      Delta32 in the child.

PMID- 12514417
TI  - Prevalence of HIV risk behaviors, risk perceptions, and testing among US adults
      with mental disorders.
AB  - Persons with mental disorders may lack the knowledge, skills, and social networks
      that help limit the spread of HIV by reducing risk behaviors. Nationally
      representative data from the 1999 U.S. National Health Interview Survey were used
      to estimate the prevalence of HIV risk behaviors among civilian
      noninstitutionalized adults with and without at least one of three psychiatric
      conditions (depression, generalized anxiety disorder, and panic attacks) in the
      previous 12 months. Relative to adults without these mental disorders, adults
      with a mental disorder (8.8% of adults nationally) were more likely to have
      engaged in HIV risk behaviors since 1980 (5.5% vs. 1.6%). Adults with a mental
      disorder were also more likely to report a high or medium chance of becoming
      infected, were more likely to have been tested for HIV infection, and were more
      likely to expect to be tested within the next 12 months.

PMID- 12514418
TI  - HIV knowledge and risk factors among men who have sex with men in Ho Chi Minh
      City, Vietnam.
AB  - OBJECTIVES: To describe health risk behavior, knowledge, and attitudes about
      HIV/AIDS and its prevention in men who have sex with men (MSM) in Ho Chi Minh
      City (HCMC), Vietnam. METHODS: A cross-sectional survey of 219 MSM using a
      standardized questionnaire. RESULTS: Men who have sex with men were easy to
      locate and willing to answer detailed questions about their sexual behavior. Self
      identified sexual orientation was 67% homosexual, 31% bisexual, and 1.4%
      heterosexual. High-risk sexual behavior was common. The mean number of sexual
      partners was 3.3 in the previous month and 14.8 in the previous year. Only 32%
      used condoms during their last intercourse, and only 40% used a condom when their
      last intercourse included anal sex. Eighty-one percent reported sex with
      nonregular male partners, and 22% also had sex with women in the past year. Drug
      use other than alcohol was rare. Most correctly identified high-risk sexual
      behavior and body fluids that could transmit HIV; however, only about half knew
      that someone who appeared healthy could transmit HIV or that there was no cure
      for AIDS. Self-rated risk for HIV was very low, and fewer than one third believed
      that homosexuals in Vietnam are at increased risk for HIV. CONCLUSION: Men who
      have sex with men in HCMC are at high risk for HIV. Knowledge about HIV
      transmission and prevention could be improved. Education and interventions
      specifically aimed at MSM are needed, because education targeted at the general
      population may not reach MSM or influence their behavior.

PMID- 12514419
TI  - Social circumstances of initiation of injection drug use and early shooting
      gallery attendance: implications for HIV intervention among adolescent and young
      adult injection drug users.
AB  - To determine correlates of early shooting gallery (SG) attendance and HIV
      prevalence and incidence among new injection drug users (IDUs), baseline data
      from a prospective cohort study of street-recruited IDUs aged 15 to 30 years and
      injecting < or =5 years were used to identify early high-risk practices and
      salient social circumstances associated with early SG attendance to help in the
      design of innovative intervention strategies. Of 226 IDUs, 10.6% were HIV
      seropositive, and HIV incidence was 6.6 per 100 person-years (95% CI: 2.2-13.3).
      Median age was 25 years, and most participants were African American (64%) and
      female (61%). Using multiple logistic regression, early SG attendees were three
      times as likely to be HIV-seropositive and twice as likely to be initiated by an
      older IDU. Early SG attendees were also five times more likely to share injection
      equipment and over three times more likely to report a high-risk injecting
      network soon after initiating injection. These data suggest that young new IDUs
      who attend SGs early tend to be initiated by older high-risk IDUs and to share
      and inject within a high-risk social setting early on as well. Hence, older IDUs
      may serve as a bridge group to SGs, transmitting HIV from older to younger IDUs.

PMID- 12514420
TI  - Improved classification of recent HIV-1 infection by employing a two-stage
      sensitive/less-sensitive test strategy.
AB  - Current serologic techniques for the classification of recent HIV-1 infection
      produce some misclassifications, and, together with the loss to follow-up of
      individuals, results in decreased enrollment of HIV-infected persons into
      appropriate intervention programs. We report on the development of a
      sensitive/less sensitive (S/LS) test strategy that includes a rapid assay to
      quickly identify persons most likely to have recent infection, followed by an
      enzyme immunoassay (EIA) with exquisite specificity. The Uni-Gold Recombigen HIV
      rapid assay (UG; Trinity Biotech, Dublin, Ireland) was procedurally-modified and
      calibrated as an LS test to differentiate recent (<133 days) from established HIV
      infections using 178 samples from persons with known dates of infection. This
      method correctly classified 83.0% of recent infections, but with a high
      misclassification rate of persons with established infection. By performing the
      rapid test followed by a modified S/LS EIA, the positive predictive value of the
      combined results for recent infections was increased to 100%. This two-stage
      testing algorithm can result in an increased efficiency for the enrollment of
      recent infection cases over a standard EIA S/LS method alone due to provisional
      enrollment during an initial testing visit, and because of an increased accuracy
      for identifying truly recent infections. We conclude that the rapid S/LS assay
      provides a tool for capturing recent infection cases quickly and is particularly
      valuable in resource-limited settings, and that the two-stage strategy provides a
      more accurate identification of persons with recent HIV infection.

PMID- 12514421
TI  - Agreement analysis of variables involved in lipodystrophy syndrome definition in
      HIV-infected patients.
AB  - BACKGROUND: Lipodystrophy studies in HIV-infected patients have usually defined
      abnormalities in body fat by clinical evaluation and patient questionnaires.
      Despite the risk for bias with these subjective approaches, agreement analysis
      among the large number of variables employed was seldom performed. OBJECTIVE: To
      analyze consistency between the usual approaches for definition of abnormalities
      in body fat distribution. DESIGN: We evaluated agreement between the clinical and
      questionnaire findings for abnormalities in body fat in an HIV patient population
      under antiretroviral treatment followed in our institution, using different
      criteria for definitions of body fat abnormalities within the same data set.
      METHODS: Kappa analysis for consistency and receiver-operator characteristic
      (ROC) curve analysis were performed. RESULTS: Low levels of agreement between
      clinical and patient perspectives were observed. Only one combination of criteria
      showed adequate agreement results. The waist/hip ratio showed low levels of
      agreement with all other variables, and no clear discriminative point was
      observed by ROC curve analysis. The ratio between the trunk fat content and the
      leg fat content assessed by dual energy x-ray absorptiometry (DEXA) scan
      demonstrated better agreement and more clear discriminative values for both male
      and female patients. CONCLUSION: Agreement analyses may help in the selection of
      the subjective variable methodology and in the inclusion of consistent and
      nonredundant objective measurements for diagnosis of abnormalities in body fat.

PMID- 12514422
TI  - Relationship between antiretroviral drug plasma concentrations and viral load in
      children.

PMID- 12514423
TI  - Visceral Leishmaniasis and HIV Coinfection in Bihar, India.

PMID- 12514424
TI  - CD8+ T cell tolerance and cancer immunotherapy.
AB  - To provide protection against all foreign pathogens one can possibly encounter
      during their lifetime, the T cell repertoire has to be as diverse as possible. At
      the same time, it is desirable that the T cell repertoire remains unresponsive
      towards healthy tissues. To realize this self/nonself discriminatory property, T
      cells undergo tightly controlled selection processes during maturation in the
      thymus. The key parameter determining the outcome of these selection processes is
      the avidity of the T cells for self-MHC/self-peptide complexes expressed in the
      thymus; low avidity interactions result in positive selection, whereas high
      avidity interactions lead to negative selection. Despite the selection processes,
      self-tolerance is far from absolute. In many cases, this is due to the presence
      of self-antigen in the thymus at a level that is too low to induce thymic
      deletion. In addition, T cells with a low avidity for ubiquitously expressed self
      antigens can escape clonal deletion and enter the periphery. A thorough
      understanding of the self-specific T cell repertoire is important because many
      potential targets for cancer immunotherapy are self-proteins. In this review, the
      authors discuss the impact of self-antigen expression on the CD8+ T cell
      repertoire. An overview of the fate and functional capacities of self-specific T
      cells with specificity for tissue-restricted self-antigens and for ubiquitously
      expressed self-antigens is provided. Furthermore, the authors discuss the
      influence of negative selection on the antitumor reactivity of the mature T cell
      repertoire.

PMID- 12514425
TI  - Autoantibodies against T-Cell costimulatory molecules are produced in canine
      autoimmune diseases.
AB  - Autoantibodies to surface molecules on lymphocytes have already been described in
      various immune conditions, such as, autoimmune diseases, infections, and blood
      transfusions. Because T-cell costimulatory molecules play a central role in the
      immune response of T-cells, we investigated the presence of autoantibodies
      against T-cell costimulatory molecules in canine autoimmune diseases. In this
      study, we prepared recombinant proteins of CTLA-4 (CD152) and CD28 and
      investigated the presence of autoantibodies against them in serum samples
      obtained from dogs with various autoimmune diseases and from healthy dogs as
      controls, using the recombinant GST fusion proteins by ELISA. Anti-CTLA-4
      antibodies were found in 31.8% of patients with rheumatoid arthritis, 20% of
      patients with systemic lupus erythematosus, 12.5% of patients with pemphigus, 0%
      of patients with immune-mediated hemolytic anemia, and 0% of healthy donors. Anti
      CD28 antibodies were not found in any of the patients or healthy donors. The
      ELISA results were further confirmed by immunoblotting. The presence of anti CTLA
      4 antibodies suggests the existence of a CTLA-4-specific immune response. The
      autoantibodies against CTLA-4, demonstrated here for the first time in canine
      autoimmune diseases, may modulate the immune response in dogs with autoimmune
      diseases.

PMID- 12514426
TI  - Booster effect of interleukin-2 on natural killer 1.1+ cells stimulated by
      administration of macrophage colony-stimulating factor in mice.
AB  - The authors studied the combined effects of macrophage colony-stimulating factor
      (M-CSF) and interleukin (IL)-2 on the functions and antitumor activity of natural
      killer (NK) 1.1+ cells in vitro and in vivo. NK1.1+ cells were isolated from the
      spleen of mice treated with saline or M-CSF, and their functions (proliferation,
      production of IFN-gamma, and cytotoxicity) evaluated in vitro. Although the
      proliferation of and production by NK1.1+ cells was stimulated by the addition of
      IL-2, the cells from the M-CSF-treated mice responded better. Furthermore, the
      cytotoxicity against Yac-1 cells and B16 melanoma cells was stimulated by M-CSF
      administration and enhanced by the addition of IL-2 and IL-12. These results
      demonstrated that M-CSF treatment augmented the functions of NK1.1 cells, and IL
      2 and IL-12 boosted these activities in vitro. The authors then examined the
      effects of co-administration of M-CSF and IL-2 in vivo. The clearance of B16
      cells in lung was augmented by the administration of M-CSF but not IL-2. However,
      M-CSF + IL-2 treatment further enhanced the clearance activity. The anti
      metastatic activity was also enhanced by the M-CSF + IL-2 treatment. Furthermore,
      the survival of B16-bearing mice was prolonged by M-CSF + IL-2. These results
      suggested that administration of IL-2 boosts the functions of NK1.1+ cells, which
      are augmented preliminarily by the administration of M-CSF.

PMID- 12514427
TI  - Chemoattraction of CD34+ progenitor cells and dendritic cells to the site of
      tumor excision as the first step of an immunotherapeutic approach to target
      residual tumor cells.
AB  - The authors previously showed that C34+ progenitor cells are mobilized into the
      peripheral blood in tumor bearers. The current study used a murine Lewis lung
      carcinoma (LLC) model to examine if the CD34+ cells can be chemoattracted to a
      tumor excision site as the first step to inducing differentiation of the
      attracted CD34+ cells into immune stimulatory dendritic cells (DC). Upon tumor
      excision, gelatin sponges were implanted into the surgical site and infused with
      phosphate-buffered saline or vascular endothelial cell growth factor (VEGF). The
      implants were removed after 4, 7, 14, and 21 days and analyzed for their cellular
      content. The incorporation of VEGF into implants increased the accumulation of
      CD34+ cells early after implantation. By day 21, the CD34+ cell content declined.
      However, the numbers of DCs became increased in the VEGF-containing sponges and
      this persisted throughout the 3-week duration of the study. The VEGF-containing
      implants contained a lower percentage of CD11b+ myeloid cells for the first 2
      weeks after implantation as compared with the control implants. By 21 days,
      myeloid cell numbers declined in the control and VEGF implants. Since endothelial
      cell precursors have a common precursor with myeloid progenitor cells, the
      implants were also examined for their endothelial cell content. With increasing
      time after implantation, the number of endothelial cells and formation of vessel
      like structures became greater in the VEGF-containing implant as compared with
      the control implants. These results show the feasibility of using VEGF-containing
      sponges to attract DC precursors and to increase the number of DCs at the tumor
      excision site.

PMID- 12514428
TI  - Immune reactivity against a novel HLA-A3-restricted influenza virus peptide
      identified by predictive algorithms and interferon-gamma quantitative PCR.
AB  - The use of appropriate antigenic peptides for the most common human major
      histocompatibility complex (MHC) alleles is required for the amplification of the
      autologous cytotoxic compartment and the development of cytotoxic T cell-mediated
      immunity. The human A2 allele of the MHC plays an important role for the
      identification of peptide-specific cytotoxic T cells (CTL) against tumor and
      viral epitopes. Computer-based prediction algorithms, which are available on the
      Internet, have already proved to be applicable for the identification of novel
      CTL epitopes. Using the bioinformatics approach, the authors have identified the
      novel influenza matrix protein-derived and HLA-A3-restricted 9-mer peptide
      RLEDVFAGK capable of inducing peptide specific CTL reactivity. Peripheral blood
      mononuclear cells (PBMC) from healthy individuals and patients with lung cancer
      were pulsed with this peptide and with the well-characterized HLA-A2-restricted
      influenza A virus matrix peptide GILGFVFTL. Using quantitative PCR (TaqMan;
      Applied Biosystems, Foster City, CA, U.S.A), reactivity for both peptides was
      determined by measuring the change in type 1 cytokine (IFN-gamma) expression upon
      in vitro stimulation. Peptide-specific reactivity matched well with the
      subsequently determined MHC-class I alleles of the tested individuals. Results
      from this study indicate that the use of bioinformatics and the PCR-based
      screening system for the monitoring of T cell reactivity may allow for the
      identification of novel CTL epitopes.

PMID- 12514429
TI  - Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer.
AB  - Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in
      90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach,
      colon, and ovary. MUC1 is a target for immune intervention, because, in patients
      with solid adenocarcinomas, low-level cellular and humoral immune responses to
      MUC1 have been observed, which are not sufficiently strong to eradicate the
      growing tumor. The hypothesis for this study is that enhancing MUC1-specific
      immunity will result in antitumor immunity. To test this, the authors have
      developed a clinically relevant breast cancer model that demonstrates peripheral
      and central tolerance to MUC1 and develops spontaneous tumors of the mammary
      gland. In these mice, the authors tested a vaccine formulation comprised of
      liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate
      that when compared with untreated mice, immunized mice develop T cells that
      express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1
      tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The
      presence of MUC1-specific CTL did not translate into a clinical response as
      measured by time of tumor onset, tumor burden, and survival. The authors
      demonstrate that some of the immune-evasion mechanisms used by the tumor cells
      include downregulation of MHC-class I molecule, expression of TGF-beta2, and
      decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally,
      utilizing an injectable breast cancer model, the authors show that targeting a
      single tumor antigen may not be an effective antitumor treatment, but that
      immunization with dendritic cells fed with whole tumor lysate is effective in
      breaking tolerance and protecting mice from subsequent tumor challenge. A
      physiologically relevant spontaneous breast cancer model has been developed to
      test improved immunotherapeutic approaches.

PMID- 12514430
TI  - Anchoring cytokines to tumor cells for the preparation of anticancer vaccines
      without gene transfection in mice.
AB  - The authors have investigated a new way of combining cytokines with tumor cells
      to prepare anticancer vaccines. This method may offer an alternative to gene
      therapy approaches. It consists in anchoring recombinant cytokines to the cell
      membrane. Attachment is mediated by the transmembrane domain of diphtheria toxin
      (T) genetically fused to the cytokine and is triggered by an acid pH pulse. The
      authors found that the fusion protein T-hIL-2 anchored to the surface of tumor
      cells retained its IL-2 activity while remaining exposed for several days.
      Interestingly, vaccination of mice with these modified tumor cells induced a
      protective antitumor immunity mediated by tumor-specific cytotoxic T lymphocytes.
      This procedure presents several advantages as compared with the conventional
      approaches based on the transfection of tumor cells with cytokine genes. It does
      not require the culture of tumor cells from the patients and the selection of
      transfected clones, it eliminates the safety problems connected with viral
      vectors, and it allows the control of the amount of cytokines delivered with the
      vaccine.

PMID- 12514431
TI  - Distinctive maturation of in vitro versus in vivo anti-CD40 mAb-matured dendritic
      cells in mice.
AB  - Dendritic cells (DCs) can be matured by CD40 stimulation to upregulate their MHC
      class II/peptide complexes and costimulatory molecule surface expression to
      become adept at presenting antigen to and activating naive T lymphocytes. The use
      of anti-CD40 antibodies as adjuvants for DC-based therapy has been advanced.
      Little is known as to how DC biology in response to CD40 ligation differs between
      in vitro versus in vivo ligation. Therefore, the authors analyzed the expression
      kinetics of MHC class II (I-Ak)/HEL peptide "complex," total MHC class II, CD80,
      and CD86 on in vitro or in vivo CD40-stimulated DCs over a period of 5 days. MHC
      class II, "complex," and costimulatory molecule expression was elevated at 1 day
      in vitro and stayed high for the culture period, whereas in vivo expression of
      the cohort of molecules peaked earlier and then declined. When purified DCs were
      co-cultured in vitro with antigen-specific T cell hybridomas, the DCs had lower
      expression of total MHC class II and "complex," but did not reduce their CD80 and
      CD86 expression. The lower expression was dependent on cognate interaction as a
      non-antigen-specific T cell hybridoma was without effect. Blocking antigen
      specific MHC class II/peptide-T cell receptor (TcR) complex interaction with
      antibody inhibited the reduction of MHC class II expression on CD40-stimulated
      DCs in vitro. Overall, their studies suggest distinct response of DCs to typical
      conditions that feature anti-CD40 monoclonal antibody (mAb)-activated DCs in
      vitro or in vivo.

PMID- 12514432
TI  - CD4+CD25+ suppressor lymphocytes in the circulation of patients immunized against
      melanoma antigens.
AB  - Murine studies have suggested that a population of CD4+ T cells expressing the
      alpha chain of the interleukin (IL)-2 receptor (CD25+) are phenotypically anergic
      in response to T cell receptor stimulation and can suppress the function of CD4+
      and CD8+ T cells. Recent studies of peripheral lymphocytes from healthy human
      volunteers have identified a similar population, although little is known about
      the presence and activity of these cells in patients with cancer and their
      possible impact on anticancer immunization strategies. Thus, the authors have
      undertaken these studies in patients with metastatic melanoma undergoing
      immunizations with known melanoma antigens. CD4+ CD25+, CD4+ CD25-, and a 1:1
      ratio of these isolated T cells were stimulated with soluble anti-CD3 antibody in
      the presence of irradiated T cell-depleted PBMCs, and proliferation was assessed
      by measuring [3H]thymidine incorporation. In 13 patients, isolated CD4+CD25+ T
      cells proliferated 68% (+/- 5.8%) less than separately cultured CD4+ CD25- T
      cells. Moreover, CD4+ CD25+ T cells suppressed the proliferation of an equal
      number of cocultured CD4+ CD25+ T cells in 11 of 13 patients by an average of 60%
      (+/- 4.9%). Suppression was not seen at day three of culture and became apparent
      at days five through nine. The degree of suppression was proportional to the
      numbers of CD4+ CD25+ T cells. Addition of high-dose IL-2 reversed the
      hypoproliferative phenotype of the CD4+ CD25+ T cells and abrogated their
      suppressive function. These studies demonstrate that anergic and functionally
      suppressive CD4+ CD25+ T cells exist in patients with melanoma undergoing tumor
      antigen immunization and thus may play a role in modifying the magnitude of the T
      cell response to immunization.

PMID- 12514433
TI  - Influence of HIV-1 coinfection on effective management of abnormal vaginal
      discharge.
AB  - BACKGROUND: Reports on microbiologic cure rates following syndromic management
      (SM) of women with nonulcerative sexually transmitted infections (STIs) are
      limited. GOAL: The goal of the study was to determine the effectiveness of the
      drugs used in SM of nonulcerative STIs and bacterial vaginosis in women and to
      compare the response among those with and without HIV-1 coinfection. STUDY
      DESIGN: This was a cohort study of women with nonulcerative STIs who were treated
      according to local SM protocols. RESULTS: Of 692 women recruited, 415 (80%)
      returned 8 to 10 days later, and 290 (70%) consented to a second examination, in
      which specimens were obtained. Clinical cure was reported by 67%, and
      microbiologic cure ranged from 80% to 89% for the three discharge-causing STIs
      and was independent of HIV-1 status. Only 38% of those with bacterial vaginosis
      were cured, and HIV-1-infected women were less likely to be cured (28% versus
      52%; P < 0.001). CONCLUSIONS: Clinical and microbiologic response to SM of the
      nonulcerative STIs was not affected by HIV-1 coinfection, but cure rates for
      bacterial vaginosis were reduced.

PMID- 12514434
TI  - A new scale for measuring dynamic patterns of sexual partnership and concurrency:
      application to three French Caribbean regions.
AB  - BACKGROUND: Quantitative assessment of multiple sexual partnerships and
      concurrency may help to elucidate the large observed differences in the
      prevalence of AIDS among population subgroups and countries. GOAL: The goals of
      the study were (1) to develop a global scale of dynamic patterns of sexual
      partnerships, including concurrency with new partners and stable concurrency; (2)
      to apply this scale to three Caribbean regions characterized by different
      cumulative rates of incidence of AIDS; and (3) to compare the concurrency rates
      given by this scale with those of other published methods. STUDY DESIGN: We
      defined an individual scale based on 6 patterns of sexual behavior over the
      previous 12-month period, by using a simple algorithm to combine 7 variables. We
      then applied this scale to cross-sectional data collected from men living in
      three French Caribbean regions: Guadeloupe, Martinique, and Guyana. RESULTS: We
      found that all adults of all age classes in the three regions studied frequently
      had multiple (>2) and concurrent partnerships. The patterns of sexual behavior in
      the three regions were consistent with the respective cumulative incidence rates
      of AIDS, and a lower rate of concurrency with new partners and a higher rate of
      stable partnership concurrency were noted in Martinique, especially among 45- to
      59-year-olds. The rate of concurrent partnerships was found to depend on the
      criteria used to define them and on the observation period (a given moment, or a
      defined period). Our definition gave a higher rate of concurrency than previously
      published indicators. CONCLUSION: The proposed scale can be applied to easy-to
      collect data in cross-sectional population surveys and takes into account a wide
      variety of behaviors, including different types of concurrency.

PMID- 12514435
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae in Cuba (1995-1999):
      implications for treatment of gonorrhea.
AB  - BACKGROUND: Antibiotic-resistant strains of Neisseria gonorrhoeae, especially
      those resistant to penicillin and tetracycline, have spread with remarkable
      rapidity in many Caribbean countries. GOAL: The goal of the study was to survey
      the antibiotic susceptibilities of N gonorrhoeae strains isolated from 1995 to
      1999 in Cuba and to discuss the impact of antimicrobial resistance on the
      management of gonorrhea in the country. STUDY DESIGN: Susceptibility of the
      strains to penicillin, tetracycline, cefuroxime, ceftriaxone, ciprofloxacin,
      spectinomycin, and azithromycin were determined by an agar dilution method.
      RESULTS: Penicillin and tetracycline resistance was noted in 60.8% and 54.2%,
      respectively, of the N gonorrhoeae strains tested. A total of 63.35 (76/120) of
      the N gonorrhoeae strains exhibited plasmid-mediated resistance to penicillin,
      tetracycline, or both. Strains with chromosomally mediated resistance to these
      antibiotics accounted for 10% (12/120) of the strains. The strains were
      susceptible to ceftriaxone, cefuroxime, spectinomycin, and ciprofloxacin. One
      strain's ciprofloxacin MIC was 0.125 mircog/ml. Of the 52 strains tested, 23.1%
      displayed intermediate resistance to azithromycin. CONCLUSIONS: N gonorrhoeae
      strains exhibited a high frequency of resistance and multiresistance to
      penicillin and tetracycline. Therefore, these antibiotics should no longer be
      used to treat gonococcal infections in Cuba and should be substituted with
      effective drugs such as third-generation cephalosporins, spectinomycin, and
      fluoroquinolones. The detection of intermediate resistance to azithromycin and
      ciprofloxacin underlines the importance of periodic surveillance for
      susceptibility of N gonorrhoeae strains to antimicrobials agents used as primary
      therapy for gonorrhea.

PMID- 12514436
TI  - Risks and benefits of the internet for populations at risk for sexually
      transmitted infections (STIs): results of an STI clinic survey.
AB  - BACKGROUND: The Internet is increasingly used for the recruitment of sex
      partners, potentially leading to increased risks for sexually transmitted
      infections (STIs). Less is known about the use of the Internet as a resource for
      STI education and prevention. GOAL: To evaluate the use of the Internet for sex
      seeking and STI information purposes by clients of a large STI clinic. STUDY
      DESIGN: A 10-item survey was conducted among clients of the Denver Metro Health
      (STI) Clinic who visited the clinic for a new problem between September 2000 and
      May 2001. RESULTS: Among 4,741 clients surveyed, 2,159 (45.5%) had Internet
      access. Of these, 138 (6.4%) reported to have gone on-line with the specific
      purpose of finding a sex partner and 146 (6.8%) reported having sex with a
      partner they found over the Internet. Internet sex-seeking was more common among
      men who have sex with men (MSM; 77/269, or 28.6%) than among men who have sex
      with women (MSW; 52/1,176, or 4.4%; P < 0.0001) and higher among MSW than among
      women (9/714, or 1.3%; P < 0.001). The Internet was accessed by 604 persons
      (28.0%) to find information on STIs. Of these, 65.1% did so for general STI
      information, 36.3% for information on HIV, 25.7% for information on genital
      herpes, 22.4% for information on chlamydia, 21.7% for information on HPV, 19.9%
      for information on gonorrhea, 16.1% for information on syphilis, and 9.3% for
      other information. Of persons seeking sex, 54.4% accessed the Internet for STI
      information, compared to 26.2% of persons not seeking sex (P < 0.0001).
      CONCLUSIONS: Among STI clinic clients in Denver, nearly half have access to the
      Internet. Sex-seeking appears to be most prevalent among MSM. Internet use for
      STI information is common among those with Internet access and even more
      widespread among those who access the Internet to seek sex. Research is needed to
      develop and evaluate Internet-based STI-prevention interventions.

PMID- 12514437
TI  - Demonstration of declining community prevalence of Chlamydia trachomatis
      infection using sentinel surveillance.
AB  - BACKGROUND: Chlamydia trachomatis infection rates in Alabama increased
      dramatically from 1996 to 1998, due in part to expanded screening. Detection of
      prevalent infection through increased testing could mask timely detection of the
      impact of screening programs on community prevalence. GOAL: The goal of the study
      was to evaluate the temporal trend in prevalence among women aged 15 to 34 years
      attending reproductive healthcare clinics in Birmingham, Alabama. STUDY DESIGN:
      Between 1995 and 1998, systematic screening of the first 60 women presenting each
      month to each of six participating clinics was performed with urine-based testing
      for chlamydia. RESULTS: In contrast to the 218% increase in chlamydia prevalence
      detected through passive surveillance, during the study period surveillance in
      sentinel sites revealed that first-visit chlamydia prevalence declined from 12.8%
      to 8.6%. CONCLUSIONS: Sentinel site surveillance served as a valuable adjunct to
      passive surveillance for determining the true trend of chlamydia prevalence
      during the hyperendemic phase of a local epidemic.

PMID- 12514438
TI  - Antimicrobial susceptibilities of Neisseria gonorrhoeae strains isolated in Java,
      Indonesia.
AB  - BACKGROUND: Despite the rapid spread of antibiotic resistance in gonococci all
      over Southeast Asia, there is only limited surveillance for antibiotic
      susceptibility in Indonesia. GOAL: This study was undertaken to determine the
      frequency and diversity of antimicrobial resistance in gonococcal isolates from
      cohorts of female commercial sex workers in Bandung and Jakarta, Indonesia, and
      to characterize the Tet M plasmid among the tetracycline-resistant strains N
      gonorrhoeae. STUDY DESIGN: The antimicrobial susceptibility of 267 strains (85
      strains from Bandung and 182 from Jakarta) to penicillin, spectinomycin,
      tetracycline, ciprofloxacin, cefotaxime, thiamphenicol, kanamycin, azithromycin,
      and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined by agar dilution.
      Typing of the Tet M plasmid in tetracycline-resistant isolates was performed by
      PCR. RESULTS: Prevalence of penicillin and tetracycline resistance was extremely
      high: 60.0% of the isolates from Bandung and 70.9% of the isolates from Jakarta
      were resistant to penicillin. Of these, 60.0% and 62.1%, respectively, were
      penicillinase-producing N gonorrhoeae (PPNG). All the isolates from Bandung and
      98.4% from Jakarta were resistant to tetracycline. All tetracycline-resistant
      isolates from Bandung and 97.8% from Jakarta carried a PCR fragment
      characteristic of the "Dutch" type Tet M plasmid. One isolate from Jakarta showed
      chromosomal resistance to tetracycline (0.6%). Chromosomal resistance to
      thiamphenicol (MIC, >/=2.0 microg/ml) was significantly higher in Jakarta than in
      Bandung (P < 0.05). All gonococcal isolates were susceptible to kanamycin,
      spectinomycin, cefotaxime, ciprofloxacin, and azithromycin. CONCLUSION:
      Spectinomycin, fluoroquinolones, and azithromycin are still useful primary drugs
      for treatment of gonococcal infections in Indonesia. Continued surveillance of
      antimicrobial susceptibility should be part of gonorrhea control in Indonesia.

PMID- 12514439
TI  - Adherence to CDC STD guideline recommendations for the treatment of Chlamydia
      trachomatis infection in two managed care organizations.
AB  - BACKGROUND: The extent of adherence to the Centers for Disease Control and
      Prevention (CDC) STD guidelines by clinicians practicing in managed care settings
      is unknown. GOAL The goal was to assess adherence to the CDC guideline
      recommendations for the treatment of genital chlamydial infection, by clinicians
      at two group model managed care organizations. DESIGN: Retrospective cohort study
      of men and women with laboratory-confirmed chlamydial infection. Patients were
      members of either the Kaiser Permanente Foundation Health Plan of Colorado or
      HealthPartners of Minneapolis/St. Paul who had tested positive for cervical or
      urethral chlamydial infection during the period from January 1, 1998, through
      June 30, 1999. RESULTS: During the study period, 1,078 patients with positive
      tests for genital Chlamydia trachomatis were identified. More than 97% of men and
      nonpregnant women and more than 98% of pregnant women were prescribed treatment,
      consistent with current CDC guidelines. CONCLUSION: Adherence to CDC-recommended
      therapy was high for patients with genital chlamydial infections at these two
      managed care organizations.

PMID- 12514440
TI  - Hepatitis C seroprevalence and risk behaviors in patients attending sexually
      transmitted disease clinics.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major global problem, transmitted
      primarily by percutaneous exposure to contaminated blood. GOAL: The goal of the
      study was to determine the seroprevalence of and risk factors for HCV among
      patients attending two urban STD clinics in Alberta. STUDY DESIGN: Anonymous
      unlinked serosurveys were performed with use of leftover sera. Self-administered
      questionnaires collected information on demographics, sexual behaviors, and drug
      use. RESULTS: The seroprevalence of HCV was 3.4% (209 of 6,668 patients).
      Univariate analysis revealed that infection was higher among nontherapeutic
      needle users (RR = 80.9), those coinfected with HIV (RR = 8.09), individuals over
      the age of 20 years (RR = 6.68), those of aboriginal ethnicity (RR = 5.54), those
      with a history of STD (RR = 3.43), men (RR = 2.2), and bisexuals (RR = 2.23). Not
      utilizing condoms and engaging in prostitution or exchanging money or drugs for
      sex were also risk factors. In multivariate analysis, nontherapeutic needle use
      remained highly significant (RR = 60.54-65.51). Other significant factors
      included sex, age, ethnicity, a history of STD, and HIV infection (RR = 1.72,
      4.62, 3.18, 1.69, and 2.56, respectively). Sexual orientation and sexual
      practices were not significant without a history of drug use. CONCLUSION:
      Nontherapeutic needle use is the strongest predictor of HCV infection.

PMID- 12514441
TI  - The social organization of commercial sex work in Moscow, Russia.
AB  - BACKGROUND: Increased poverty, unemployment, and migration place the Russian
      population at high risk for sexually transmitted infections (STIs). A qualitative
      study was undertaken to clarify the organization of sex work and describe the
      likely contributions of different types of sex work to disease transmission.
      GOAL: The goal of the study was to describe the social-organizational patterns of
      sex work in Moscow, Russia. STUDY DESIGN: Four qualitative data collection
      methods were used: semistructured telephone interviews, semistructured face-to
      face individual and group interviews with key informants, systematic and
      unobtrusive naturalistic observations, and geomapping. RESULTS: Intermittent,
      truck stop, and railway station sex workers may be the most important groups in
      the dissemination of STIs. Sex work is widely disseminated throughout the city.
      Identifiable positions in the social organization of street sex work include
      pimps, assistant female pimps, guards, drivers, "indicators," the sex workers
      themselves, and recruitment "pluckers." CONCLUSION: The Moscow sex market may be
      an adjustive response of the social system to the economic pressures in Russia.
      Sex work in Moscow has great potential for disseminating STIs throughout Russia
      and beyond. Understanding of these issues may enhance the impact of STI
      prevention programs.

PMID- 12514442
TI  - Injection drug use, commercial sex work, and the HIV/STI epidemic in the Russian
      Federation.

PMID- 12514443
TI  - Patient-delivered partner treatment with azithromycin to prevent repeated
      Chlamydia trachomatis infection among women: a randomized, controlled trial.
AB  - BACKGROUND: Repeated infection with C trachomatis increases the risk for serious
      sequelae: pelvic inflammatory disease, ectopic pregnancy, infertility, and
      chronic pelvic pain. A substantial proportion of women treated for C trachomatis
      infection are reinfected by an untreated male sex partner in the first several
      months after treatment. Effective strategies to ensure partner treatment are
      needed. GOAL: The goal of the study was to determine whether repeated infections
      with C trachomatis can be reduced by giving women doses of azithromycin to
      deliver to male sex partners. STUDY DESIGN: A multicenter randomized controlled
      trial was conducted among 1,787 women aged 14 to 34 years with uncomplicated C
      trachomatis genital infection diagnosed at family planning, adolescent, sexually
      transmitted disease, and primary care clinics or emergency or other hospital
      departments in five US cities. Women treated for infection were randomized to one
      of two groups: patient-delivered partner treatment (in which they were given a
      dose of azithromycin to deliver to each sex partner) or self-referral (in which
      they were asked to refer their sex partners for treatment). The main outcome
      measure was C trachomatis DNA detected by urine ligase chain reaction (LCR) or
      polymerase chain reaction (PCR) by 4 months after treatment. RESULTS: The
      characteristics of study participants enrolled in each arm were similar except
      for a small difference in the age distribution. Risk of reinfection was 20% lower
      among women in the patient-delivered partner treatment arm (87/728; 12%) than
      among those in the self-referral arm (106/726; 15%); however, this difference was
      not statistically significant (odds ratio, 0.80; 95% confidence interval, 0.62
      1.05; = 0.102). Women in the patient-delivered partner treatment arm reported
      high compliance with the intervention (82%). CONCLUSION: Patient-delivered
      partner treatment for prevention of repeated infection among women is comparable
      to self-referral and may be an appropriate option for some patients.

PMID- 12514444
TI  - Correlates of continued risky sex among pregnant African American teens:
      implications for STD prevention.
AB  - BACKGROUND: African American adolescent females have been understudied with
      regard to their continued sexually transmitted disease (STD) risk behavior during
      pregnancy. Preintervention studies of this population are especially important
      because the sequelae of STDs during pregnancy can be particularly problematic.
      OBJECTIVE: This exploratory study identified correlates of engaging in relatively
      frequent penile-vaginal sex, unprotected by a condom, among inner-city African
      American adolescents during their first or second trimester of pregnancy. STUDY
      DESIGN: Baseline data collected as part of an HIV prevention study were used.
      Adolescents at their first prenatal visit completed a self-administered survey
      and face-to-face interview. Only adolescents reporting a current boyfriend were
      included in this exploratory analysis (n = 144). Significant bivariate correlates
      were assessed for multivariate significance. RESULTS: Significant bivariate
      correlates of relatively frequent unprotected vaginal sex were older age (P <
      0.02), primiparity (P < 0.03), not being enrolled in school (P < 0.02), not
      residing with at least one parent (P < 0.001), reported infrequent sexual
      communication (communicating about sex) with the boyfriend (P < 0.01), spending
      at least 30 hours each week with the boyfriend (P < 0.001), reporting that the
      age of the current relationship was at least 2 years (P < 0.04), and using
      marijuana in the past 30 days (P < 0.03). Three correlates retained significance
      in the multivariate model: not residing with at least one parent (adjusted odds
      ratio [AOR] = 2.24; P < 0.04), spending at least 30 hours with the boyfriend each
      week (AOR = 3.70; P < 0.002), and infrequent sexual communication with the
      boyfriend (AOR = 2.88; P < 0.008). CONCLUSION: Given the potential of STDs to
      complicate pregnancy outcomes, clinic-based and community-based programs
      addressing relational dynamics and relational obstacles to safer sex may be
      warranted, particularly for adolescents not residing with parents.

PMID- 12514445
TI  - Surveillance of Chlamydia trachomatis and Neisseria gonorrhoeae infections in
      women in detention in Baltimore, Maryland.
AB  - BACKGROUND: In conjunction with a program to expand syphilis and HIV infection
      services, women were also offered screening for Chlamydia trachomatis (CT) and
      Neisseria gonorrhoeae (GC) during intake at the Baltimore Women's Detention
      Center. GOAL: The goal was to assess the effectiveness of a routine screening
      program for CT and GC in women in a detention setting. The association among
      infection, race, and area of residence was also explored. STUDY DESIGN: CT and GC
      prevalences were determined and analyzed by demographic data, including zipcode,
      for 1,858 women enrolled over a 48-week period. Informed consent was obtained,
      and infections were detected with use of urine samples tested by ligase chain
      reaction. RESULTS: Overall, the population had prevalence rates of 5.9%
      (109/1,858) and 3.4% (63/1,858) for CT and GC respectively. Among whites, CT and
      GC prevalences were 9.0% (29/323) and 8.7% (28/323), respectively. Among African
      Americans the prevalence rates were 5.1% (77/1,510) and 2.3% (34/1,510) for CT
      and GC, respectively. White women <25 years of age were associated with the
      highest CT and GC prevalences, at 20.0% (13/65) and 13.9% (9/65), respectively.
      African American women <25 years of age also were associated with the highest CT
      and GC prevalences, at 13.9% (24/173) and 5.8% (10/173), respectively.
      Multivariate analysis of risk factors and demographic data indicated that ages
      <25 years and 25 to 34 years, white race, and certain zipcodes of residence were
      risk factors for infection. CONCLUSION: This study illustrated that urine-based
      screening for CT and GC is feasible in detention settings and can be productive
      in high-prevalence areas. Geographic analysis demonstrated no definitive
      relationship among race, infection, and area of residence, although it did
      demonstrate clustering of infected individuals and could be useful in future
      interventions. These findings demonstrated the need for implementing screening
      programs for sexually transmitted infections in detention centers.

PMID- 12514446
TI  - Why women douche and why they may or may not stop.
AB  - BACKGROUND: Although douching is common, it is a potentially harmful habit. GOAL:
      We studied attitudes and knowledge around the behavior of douching. STUDY DESIGN:
      Of 1,200 women enrolled in this multisite study, 532 douched and answered
      questions on a structured interview regarding douching behaviors. RESULTS: Over
      half had douched for 5 or more years. Douching was most often initiated on the
      recommendation of female relatives and practiced for reasons of hygiene. Half of
      women considered douching to be healthy. Those who considered douching to be
      unhealthy reported that douching may disrupt vaginal flora but did not cite more
      serious risks. Nonetheless, women who had been advised by a health professional
      to stop douching were less likely to consider douching healthful and were more
      likely to have tried to stop. CONCLUSION: Women had a limited understanding of
      potential adverse health consequences associated with douching. Targeted health
      messages may influence women to initiate douching cessation.

PMID- 12514447
TI  - Partner notification for HIV and syphilis: effects on sexual behaviors and
      relationship stability.
AB  - BACKGROUND: Partner notification (PN), originally designed for syphilis control,
      has been used to control the spread of HIV since 1985. Because HIV infection is
      noncurable, the benefit of contact tracing and treatment demonstrated for the
      control of syphilis may not apply to HIV. For HIV, PN must facilitate behavior
      change that will reduce the spread of the infection. One concern is that HIV PN
      can promote the breakup of old partnerships and increase the acquisition of new
      partners, thereby spreading HIV infections. GOAL: The purpose of this study was
      to determine the effect of partner notification (PN) on sexual behavior and
      relationship stability among HIV partnerships, with use of syphilis partnerships
      for comparison. STUDY DESIGN: Partnerships were eligible if the index case was
      interviewed by a disease intervention specialist (DIS) for PN and named at least
      one sex partner. Partnership information was reported by index cases interviewed
      at baseline and 3 and 6 months post-PN. Trends in partnership dissolution and
      acquisition, sexual abstinence, condom use, emotional abuse, and physical
      violence reported by HIV infection and syphilis index cases were compared.
      RESULTS: A total of 157 index cases (76 HIV infection and 81 syphilis) reported
      220 partnerships (94 HIV and 126 syphilis). The PN process was completed for
      32.7% of partnerships and it was completed more often for partnerships that were
      classified as main and cohabiting. After PN, 46.8% of partnerships dissolved,
      15.9% of cases acquired a new partner, and emotional abuse and physical violence
      decreased significantly. HIV index cases were somewhat more likely to report
      using condoms at last sex act and less likely to acquire a new sex partner after
      PN compared to syphilis index cases. There was no difference post-PN between HIV
      infection and syphilis partnerships for partnership dissolution, physical
      violence, emotional abuse and abstention from sex. CONCLUSION: HIV PN did not
      appear to cause greater partnership dissolution, new partner acquisition, or
      violence compared with syphilis PN.

PMID- 12514448
TI  - Changes in partnerships and HIV risk behaviors after partner notification.
AB  - BACKGROUND AND OBJECTIVE: Few studies have examined the effect of partner
      notification (PN) on behavior change and partnerships. This study investigated
      both. GOAL: The goal was to examine the effect of PN on sexual behaviors and
      partnership dissolution and formation. STUDY DESIGN Subjects included HIV
      positive persons interviewed to identify partners for notification, partners
      notified of exposure, and HIV-negative persons receiving HIV counseling and
      testing (controls). Subjects were interviewed about behaviors and relationships
      at baseline and at 3- and 6-month visits. Partnerships in which both subject and
      partner received PN were compared to partnerships in which only the subject
      received PN and to control partnerships. RESULTS: Partnerships where both persons
      received PN were less likely to break up or acquire new partners and more likely
      to use condoms at follow-up. CONCLUSION: PN did not increase partnership
      dissolution or formation and was associated with higher condom use, suggesting
      the value of PN in HIV prevention.

PMID- 12514449
TI  - Partner notification for HIV: running out of excuses.

PMID- 12514450
TI  - Patterns and predictors of female condom use among ethnically diverse women
      attending family planning clinics.
AB  - BACKGROUND: The female condom is a viable option for women to protect themselves
      from HIV infection and other sexually transmitted diseases. GOAL: The goal was to
      examine the level of female condom use and factors associated with frequency of
      use among US women living in San Francisco and Oakland, California. STUDY DESIGN:
      Of 238 women recruited from family planning clinics from July 1998 to April 1999,
      206 were interviewed at both baseline and 3-month follow-up (a 92% retention
      rate). RESULTS: We observed a significant increase in vaginal sexual acts
      protected by the female condom during the study but no reduction in male condom
      use. Overall, 82% of women reported using a female condom at least once, but the
      proportion of sexual acts protected by the female condom was only 17%.
      Multivariate analyses showed that female condom use was associated with
      suggesting female condom use to one's partner, less concern about device
      appearance, and a partner's positive attitude about the female condom.
      CONCLUSION: Our data indicate that female condom use supplements male condom use
      and leads to an increase in protected sex. The results also suggest that
      attitudinal and communication factors can increase female condom use.

PMID- 12514452
TI  - Chronic pain secondary to disability: a review.
AB  - BACKGROUND: Until recently, very little has been written regarding chronic pain
      as a secondary problem in persons who already have a physical disability, despite
      the potential for pain to increase the negative impact of what may already be a
      very disabling condition. The purpose of this review is to summarize what is
      currently known concerning the nature and scope of chronic pain as a secondary
      condition to disability, specifically spinal cord injury, acquired amputations,
      cerebral palsy, multiple sclerosis, neuromuscular disease, and postpolio
      syndrome. METHOD: What is known concerning the frequency, severity, impact, and
      treatment of pain in these specific conditions is reviewed, as are the factors
      that contribute to, or are associated with, adjustment to chronic pain in these
      disability groups. The authors conclude with several research questions that
      emerge from this knowledge, the answers to which will contribute to the long-term
      goal of the reduction of pain and suffering in persons with disabilities.
      CONCLUSIONS: The existing literature clearly documents that many persons with
      disabilities experience chronic pain. Many questions remain unanswered regarding
      the scope, severity, and treatment of chronic pain in these groups.

PMID- 12514453
TI  - Psychosocial predictors of physical performance in disabled individuals with
      chronic pain.
AB  - OBJECTIVES: First, to identify what physical performance differences existed
      between a group of disabled individuals with chronic pain and a control group of
      pain-free individuals with comparable disabilities; and second, to test a
      psychosocial model designed to evaluate which psychosocial constructs were
      predictive of performance in disabled individuals with chronic pain. DESIGN: Case
      comparison study. SETTING: Ambulatory university laboratory. PARTICIPANTS: A
      community sample of 62 individuals with lower limb amputations or paraplegia, 31
      with chronic pain and 31 pain-free. INTERVENTION: Standardized lifting and wheel
      turning tasks. MAIN OUTCOME MEASURES: Static strength, endurance, lifting speed,
      lateral and anterior-posterior sway, and multidimensional psychosocial measures.
      RESULTS Disabled individuals with chronic pain had decreased endurance for both
      the lifting (p <0.001) and the wheel-turning (p <0.05) tasks. A psychosocial
      model of physical performance also was evaluated. Using confirmatory factor
      analysis, 31 measures were used to validate 8 theoretical constructs: emotional
      functioning, pain intensity, pain cognitions, physical functioning, social
      functioning, task-specific self-efficacy, performance outcome, and performance
      style. Regression analyses indicated that more than 90% of the variance in
      performance was predicted by psychosocial factors, with self-efficacy, perceived
      emotional and physical functioning, pain intensity, and pain cognitions showing
      the highest associations. CONCLUSIONS: Chronic pain was found to significantly
      reduce the performance in individuals with lower limb amputations and paraplegia.
      A strong association was found between performance and psychosocial factors in
      disabled individuals with chronic pain. These findings extend the existing
      literature by validating that psychosocial models of chronic pain can be applied
      to the disabled population, with results similar to those of other chronic pain
      samples.

PMID- 12514454
TI  - Factors associated with willingness to try different pain treatments for pain
      after a spinal cord injury.
AB  - OBJECTIVE: To develop and establish the psychometric properties of a pain
      treatment willingness scale and identify factors associated with willingness to
      try specific pain treatments for spinal cord injury (SCI)-related pain. DESIGN:
      As part of a larger study, a questionnaire was designed to assess willingness to
      use various pain medications and other types of pain treatments. This
      questionnaire, which included measures of pain severity, pain interference, mood,
      hope, and current use of pain treatments, was completed by persons with SCI
      recruited through the mail or in person. SUBJECTS: One hundred fifteen persons
      completed the questionnaire (35% response rate). Seventy-two percent of the
      participants were men, mean age was 49.1 years, and average time elapsed since
      injury was 8 years. RESULTS: Factor analysis indicated two factors-willingness to
      use opioids and willingness to use nonpharmacological treatment (i.e., physical
      therapy, relaxation methods and stress management, and alternative medicine).
      Internal consistency and convergent and divergent validity were established.
      Persons experiencing SCI-related pain were more willing to use pain treatments
      than those without current pain, and those who were currently using opioids
      reported greater willingness to use that treatment. Persons who reported SCI
      related pain were more willing to use nonpharmacological treatments than opioid
      medications. Finally, participants demonstrated different degrees of willingness
      to use an opioid medication based on its name (i.e., "narcotic," "codeine,"
      "morphine," "methadone"). CONCLUSIONS: Willingness to use a specific pain
      treatment may be a key factor mediating the behavior of using that specific
      treatment. Assessment of patient attitudes toward various treatments options,
      particularly regarding opioid medications, is warranted to optimize treatment
      adherence. Once the factors that determine these attitudes are identified,
      interventions to increase willingness to use nonpharmacological or opioid
      treatments can be designed and evaluated.

PMID- 12514455
TI  - Chronic pain and nonpainful sensations after spinal cord injury: is there a
      relation?
AB  - OBJECTIVES: First, to define the clinical characteristics of nonpainful
      sensations (NP) that commonly appear after spinal cord injury (SCI); and second,
      to compare the clinical characteristics of NP and chronic pain (CP) after SCI.
      METHODS: Two sets of questions concerning CP and NP were mailed to 330 subjects.
      Responses from 197 persons experiencing CP as well as NP were analyzed. RESULTS:
      The most common locations for CP and NP were back and lower extremities. Although
      the number of areas in which the subjects perceived CP and NP to be located was
      significantly correlated, a factor analysis showed separate groupings of areas
      with CP and NP, respectively. Self-reported allodynia or hyperesthesia in the
      lower extremities, however, was significantly associated with CP in the same
      areas. The number of descriptive adjectives used for CP and NP was also
      significantly correlated, as was the perceived intensity of CP versus NP.
      Additionally, significant correlations were found in onset and temporal pattern
      of CP and NP. Similarly to CP, NP interfered with sleep, work, and other daily
      activities, and the patterns of interference due to CP and NP were significantly
      correlated. DISCUSSION: While many aspects of the clinical picture of CP and NP
      are similar after SCI, the CP and spontaneous NP are not necessarily located in
      the same areas. Although the observed similarities between CP and NP may be based
      on pathophysiologic mechanisms, the significant relations between the
      interference patterns suggest that psychosocial mechanisms related to coping are
      also involved.

PMID- 12514456
TI  - A review of chronic pain after inguinal herniorrhaphy.
AB  - BACKGROUND: Chronic pain was believed to be a recognized but infrequent
      complication after inguinal hernia repair. Evidence suggests that patients with
      chronic pain place a considerable burden on health services. However, few
      scientific data on chronic pain after this common elective operation are
      available. OBJECTIVES: To review the frequency of chronic pain and to discuss
      etiological theories and current treatment options for patients with chronic post
      herniorrhaphy pain. MATERIALS AND METHODS: All studies of postoperative pain
      after inguinal hernia repair with a minimum follow-up period of 3 months,
      published between 1987 and 2000, were critically reviewed. RESULTS AND
      DISCUSSION: The frequency of chronic pain after inguinal hernia repair was found
      to be as high as 54%, much more than previously reported. Quality of life of
      these patients is affected. Chronic pain is reported less often after
      laparoscopic and mesh repairs. Recurrent hernia repair, preoperative pain, day
      case surgery, delayed onset of symptoms, and high pain scores in the first week
      after surgery, however, were identified to be risk factors for the development of
      chronic pain. Definition of chronic pain was not explicit in the majority of the
      reviewed studies. Accurate evaluation of the frequency of chronic pain will
      require standardization of definition and methods of assessment. Prospective
      studies are required to define the role of risk factors identified in this
      review.

PMID- 12514457
TI  - Differential analgesic effect of tenoxicam on the wound pain and uterine cramping
      pain after cesarean section.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to
      enhance opioid analgesia in the acute pain service. The question, however, of
      whether NSAIDs produce a similar extent of potentiation among different types of
      pain, has not been thoroughly investigated. MATERIALS AND METHODS: A randomized,
      placebo-controlled, double-blind study was performed to characterize the
      analgesic effect of tenoxicam, a long-acting NSAID, on resting wound pain, evoked
      wound pain, and uterine cramping pain after cesarean section. Saline (n = 48) or
      20 mg tenoxicam (n = 45) was intravenously injected immediately after clamping
      the umbilical cord. All patients were instructed to obtain maximal postoperative
      analgesia by intravenous patient-controlled morphine. RESULTS Tenoxicam
      profoundly reduced the intensity of uterine cramping pain (3.6 [2.0-5.6] versus
      5.5 [3.4-6.6]; p < 0.01) but had no additional effect on wound pain at rest, with
      movement, changing position, sitting, and walking. Intraoperative injection of 20
      mg tenoxicam decreased the demand ratio for patient-controlled analgesia (PCA)
      and 24-hour morphine consumption by approximately 30%. CONCLUSIONS: The data show
      that tenoxicam potentiates opioid analgesic effect on the somatic and visceral
      types of pain to different extents, and they suggest that intraoperative
      injection of 20 mg tenoxicam is sufficient to enhance intravenous PCA morphine on
      uterine cramping pain for the first 24 hours after cesarean section.

PMID- 12514458
TI  - The rationale and use of topiramate for treating neuropathic pain.
AB  - OBJECTIVE: To outline the modes of action of topiramate and to examine the
      theoretical reasons as to why topiramate may alleviate neuropathic pain. Results
      of animal and human studies in the use of topiramate for treating pain are
      reviewed, together with case studies describing situations where topiramate was
      effective when other treatments have failed. CONCLUSIONS: Topiramate acts on
      neuronal transmission in at least five ways: by modulating voltage-gated sodium
      ion channels, potentiating gamma-aminobutyric acid inhibition, blocking
      excitatory glutamate neurotransmission, modulating voltage-gated calcium ion
      channels, and by inhibiting carbonic anhydrase. This review suggests that there
      are good theoretical reasons for a trial of topiramate in patients with
      neuropathic pain where conventional medical treatments have failed. Although not
      currently licensed for treating pain, topiramate should be considered before
      invasive methods of pain relief are contemplated. Most of the side effects of
      topiramate are dose dependent, but by starting medication with a low dose (</=25
      mg/d) that is gradually titrated upward, tolerance is much more easily achieved.

PMID- 12514459
TI  - Complex regional pain syndrome type I associated with amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: (CRPS I [formerly called reflex sympathetic dystrophy]) is a syndrome
      with pain and signs of autonomic dysfunction after trauma or immobilization; the
      pathophysiologic mechanisms of CRPS I, however, remain unknown. DESIGN: The
      authors present a case of CRPS I associated with amyotrophic lateral sclerosis.
      Along with the motor paresis due to amyotrophic lateral sclerosis, pain,
      swelling, and signs of autonomic disturbance occurred. CONCLUSIONS: This case
      supports the hypothesis that immobilization is one of the major contributing
      factors for CRPS I.

PMID- 12514460
TI  - Self management in palliative care.

PMID- 12514461
TI  - An evaluation of teamwork within a specialist palliative care unit.
AB  - This small-scale 10-month study evaluated teamworking within a specialist
      palliative care team. The study aims were to: collect, analyse and summarize
      information on how team members perceive teamworking; compare team members'
      perceptions after a teambuilding workshop; and to evaluate the longer term effect
      of this training on the team. A group of practitioners from a local Marie Curie
      Cancer Care Centre was selected and included members from all available
      disciplines. A piloted questionnaire was used to obtain qualitative and
      quantitative input. The team as a whole scored themselves above average on almost
      all counts. Following the teambuilding workshop significant improvement was seen
      in areas such as role appreciation and communication but not all improvements
      were long lasting. A perception of understaffing was noted as being one of the
      largest negative influences on teamwork whereas the setting and maintaining of
      agreed team objectives and having sufficient education opportunity were positive
      influences. Although teambuilding sessions appear to have the potential to
      produce the desired benefits, they should not be initiated at a time when staff
      already feel anxiety over their workload.

PMID- 12514462
TI  - Palliative care for Muslims and issues before death.
AB  - National and European directives have now enshrined within European law the
      requirement that healthcare professionals provide their patients with culturally
      appropriate and sensitive care. Although well intentioned, many health
      professionals find it difficult to translate these directives into practice.
      Barriers to providing culturally competent care include racism, institutional
      discrimination and gaps in our understanding of the interface between culture and
      health--this latter factor reflecting the lack of training in transcultural
      health care. In this paper, we concentrate on issues relating to the provision of
      palliative care near death to Muslims of South Asian origin in the UK, although
      much of what is said will equally be applicable to Muslims from other parts of
      the world. This is the first of two articles giving insights into the palliative
      care of Muslims. The second article 'Palliative care of Muslims and issues after
      death' will appear in a later issue.

PMID- 12514463
TI  - Good death? An exploration of newly qualified nurses' understanding of good
      death.
AB  - The dominant professional understanding of good death is death where symptoms are
      controlled, the inevitability of death has been accepted and preparations have
      been made leading to peace for all involved. It seems surprising, in a
      pluralistic society, that there might be such a clear common understanding of
      good death. This study looks at the understandings of good death voiced by 28
      staff nurses who were interviewed about their experiences of caring for dying
      people in hospital. The findings suggest that a nurse's understanding of good
      death had elements that were shared with her colleagues, but also that there was
      a personal understanding of a good death. The concept of good death is perhaps a
      reduction of the acceptable way to care for a dying person. The concept of
      'personally ideal death' is proposed as a refinement of good death that
      recognizes that the beliefs and values of each individual influences what they
      understand to be acceptable death.

PMID- 12514464
TI  - Use of quality-of-life scores in care planning in a hospice setting: a
      comparative study.
AB  - This study examined the concept and measurement of quality of life (QOL) in
      terminally ill patients. It also addressed how patients' QOL can be improved
      within a hospice setting. Measurement of QOL was used in developing patient-care
      plans and to identify differences in QOL assessment between nurse and patient as
      an aid to reflective practice. The findings of the study revealed that a better
      understanding of the patient can be achieved if nurses have access to the
      patient's QOL perspective. This better understanding, when translated into
      meeting patients' QOL priorities and needs, resulted in clinically significant
      improvements in their QOL. Reflective practice by nurses was also shown. A second
      article will discuss how the theme 'revelation' emerged from the insights of
      those involved in the study.

PMID- 12514465
TI  - Factors associated with falls in an inpatient palliative care unit: an
      exploratory study.
AB  - In one inpatient palliative care unit falls were identified as a frequent and
      distressing, yet potentially avoidable, concern. The unit had the highest rate of
      falls in this long-term care setting, exceeding even that of dementia care units.
      No literature could be identified that examined falls in the palliative care
      population. The objective of the exploratory study was to examine factors
      associated with falls through retrospective archival data collection. Detailed
      information was collected on all 177 falls that occurred in the unit in 1999.
      Data were also gathered on patients who had not fallen for comparison. Analysis
      was conducted comparing risk factors of those patients who fell once and those
      who fell multiple times. It was found that advanced age, longer length of stay
      and a previous history of falls might be risk factors for future falls. Patients
      who fell multiple times had less symptom distress than patients who fell once.

PMID- 12514466
TI  - RCN's definition of nursing: what makes nursing unique?

PMID- 12514467
TI  - Perioperative care is failing patients in need of surgery.

PMID- 12514468
TI  - Nurse who was not competent and who covered up her actions.

PMID- 12514469
TI  - Importance of continence advice for people with multiple sclerosis.
AB  - Bladder and bowel problems are a common feature in patients with multiple
      sclerosis (MS). This article demonstrates how patients benefit from specialist
      input relating to continence as part of a multidisciplinary neurological
      rehabilitation service (MNRS). The implementation of the MNRS has offered a 'one
      stop' referral system for people with an acquired or progressive neurological
      condition. The patient's condition should be such that active and effective
      rehabilitation can take place. One of the key aims of the service is to enable
      people to function as independently as possible by improving/maintaining their
      physical, social, and psychological well-being through appropriate assessment and
      treatment regimes. The Multiple Sclerosis Society recommends the involvement of
      specialist nurses and specialist multidisciplinary teams in the management of
      patients. The recommended standards suggest that people with MS should be put in
      contact with a specialist multidisciplinary team in their area where appropriate
      treatment in relation to tone management, posture, fatigue management and
      continence can be provided. Without specialist advice, patients may develop more
      serious and intractable problems in the longer term. The author will describe how
      working in a specialized team has moved towards meeting these recommendations and
      in so doing has enhanced care for people with MS.

PMID- 12514470
TI  - Risk assessment and management to ensure health and safety at work.
AB  - Mammet, the charge nurse on a surgical ward, was asked to carry out a risk
      assessment on health and safety. He had never been taught such an activity and
      needed to seek advice.

PMID- 12514471
TI  - The professional standard of care in clinical negligence.
AB  - Clinical guidelines are important healthcare quality management tools which have
      become more widely known and accepted in the NHS today. There are some problems
      with the terminology used regarding clinical guidelines and sometimes they are
      confused with protocols. Clinical guidelines have a number of legal implications
      and they could be influential in determining the standard of care to be expected
      in a particular case. The Bolam case shows that a number of care approaches are
      acceptable as long as they are reasonable. The developers of clinical guidelines
      should develop an audit trail of their work and build in review dates.

PMID- 12514472
TI  - A study to determine the qualities of a learning disability practitioner.
AB  - In recent years a number of research studies have explored the role of key
      professionals in the field of learning disability. These have been predominantly
      large studies, nationally commissioned and offering a broad structural picture of
      the professionals' current function. This article explores a localized research
      study undertaken in the Avon, Gloucestershire and North Wiltshire area of the
      south-west of England. While acknowledging the national context in which both
      learning disability nurses (RN(LDs) and social workers operate, this study offers
      a more intimate insight into what form of future practitioner would be most
      effective. The qualitative research study included a series of topic-focused
      interviews and focus groups comprising professionals, people with learning
      disabilities, carers and representatives from the voluntary and independent
      sectors. Findings established that the desired future practitioner would maintain
      the specialist way of thinking of the RN(LD), together with the care management
      facilitation role of the social worker. For the research participants the optimal
      choice of practitioner was a dually qualified RN(LD)/social worker. Although the
      study was set in a particular locality, the researchers suggest that the outcomes
      both endorse and identify tensions in the proposed national developments for
      professional education, at a crucial point for the delivery and design of health
      and social care learning disability services.

PMID- 12514473
TI  - Meeting the needs of people with learning disabilities in acute care.
AB  - This article describes the work of the Birmingham Acute Hospital Liaison Project,
      which seeks to support people with learning disabilities in acute care. Following
      the community care reforms, more and more people with learning disabilities are
      accessing mainstream primary and secondary healthcare services in community
      settings staffed by generic rather than specialist learning disability staff.
      Unfortunately, research suggests that some people with learning disabilities
      receive poor quality care and that available services are not always responsive
      to their needs. As a result, the Acute Hospital Liaison Project has a dual role:
      supporting people with learning disabilities as they enter hospital; and working
      with ward staff to equip them with the skills and confidence they need to work
      more effectively with people with learning disabilities.

PMID- 12514474
TI  - Acupuncture: evidence for its use in chronic low back pain.
AB  - Back pain is a major economic burden in the UK, with increasing numbers of
      patients seeking complementary therapies, such as acupuncture, as a means to
      supplement traditional medical treatments. Studies to date have produced
      conflicting results relating to the efficacy of acupuncture and thus this
      systematic review will provide a concise summary of the clinical scenario in
      Western countries. A search of various electronic databases identified 11
      articles consisting of three case studies, five randomized controlled trials, and
      two cross-over trials. Systematic examination of these articles did not provide
      definitive evidence to support or refute the use of acupuncture in the treatment
      of low back pain. In an era of increasing demands for evidence-based practice and
      professional accountability, the absence of irrefutable scientific evidence
      places nurses and medics in a vulnerable position.

PMID- 12514475
TI  - The concept of hope in nursing 6: research/education/policy/practice.
AB  - This article, the last in the series, focuses on future international research,
      education, policy and practice issues that centre around the concept of hope.
      While a growing literature is accumulating, it needs to be acknowledged that the
      area of hope and hope inspiration remains under-researched and is consequently
      not well understood. However, this article highlights future research questions
      around hope which have been grouped under the broad headings of: (1) the
      structure of hope; (2) the assessment of hope; (3) the enhancement of hope; (4)
      the potential outcomes of hope. The article also declares how our current body of
      knowledge relating to hope has had limited visibility outside professional
      journals, has not received the funding necessary, and has not been reflected in
      relevant policies within our healthcare and educational institutions. If the goal
      is to conduct interdisciplinary research across countries and to gain a global
      understanding of hope, then greater resources are needed. There is a need to
      prepare nurses and other healthcare professionals to deal with the challenge of
      enhancing and maintaining hope in those that they care for in their practice, as
      well as in themselves.

PMID- 12514476
TI  - Esteem one-piece closed pouch in the management of stomas.
AB  - There has been a dramatic improvement in recent years in the production of stoma
      appliance to enable the ostomist to lead a normal active life. This article will
      review the components required of a one-piece closed appliance and appraise
      ConvaTec's Esteem one-piece closed pouch.

PMID- 12514477
TI  - Nurses must ensure they communicate with clients.

PMID- 12514478
TI  - Government offers nurses 'strings attached' pay award.

PMID- 12514479
TI  - There is no such thing as a child receiving 'a good smack'.

PMID- 12514480
TI  - Nurse who started an affair with a mental health patient.

PMID- 12514481
TI  - Recovering from subarachnoid haemorrhage: patients' perspective.
AB  - Healthcare professionals generally accept that a good recovery following
      subarachnoid haemorrhage (SAH) equates to one where there is an absence of
      physical deficit. There does not appear to be a general acceptance of the impact
      of the less obvious invisible or psychological difficulties. Therefore, this
      study aimed to illuminate the experience of recovery from SAH. Using a
      qualitative methodology, eight participants were interviewed using a semi
      structured approach. Individual data were handed to the participant for the
      purpose of confirming the accuracy of the summary made by the author. Data were
      then analysed for similar and contrasting themes. As a result, the study offers
      an insight into how common psychological difficulties may impact on a person's
      ability to make a full and complete recovery following SAH. In conclusion, the
      main themes generated by the data are presented and recommendations for practice
      in meeting the needs of participants are offered.

PMID- 12514482
TI  - Clinical governance and assessing and managing clinical risk.
AB  - Joshua worked in paediatrics and was concerned about the frequency of injuries
      caused to babies as a result of intravenous fluids being pumped into the tissue.
      It appeared that the mechanical pumps were not sufficiently sensitive to cut out
      when the vein tissued and there had been several cases where it appeared that
      serious harm had been caused to a baby.

PMID- 12514483
TI  - Parents' support and satisfaction with their child's postoperative care.
AB  - It is recognized that parents' presence during their child's hospitalization is
      of benefit to the parents and the child. However, the level of parental
      involvement in their child's care may be influenced by many factors, such as the
      amount of support nurses provide for parents. This article reports on two themes
      from the findings of a larger study on parental involvement in children's
      postoperative pain management - parental support and parents' satisfaction with
      their child's postoperative pain management. The aim of the larger study was to
      explore both nurses' and parents' perceptions of parental involvement in their
      child's postoperative pain management. The methods used were both qualitative and
      quantitative. The qualitative method of phenomenology was used to guide 20 nurse
      and 20 parent interviews. Quantitative methods involved surveying the nurses and
      parents on their perceptions of how supportive the nurses were towards the
      parents. The charts of 20 children were reviewed for pain-related data. This
      article reports on the issues of parent support from the results of the survey,
      and on satisfaction relating to their child's postoperative pain management from
      the parent interviews. The findings demonstrated that nurses perceived that
      parents were receiving more support from them than that which parents felt they
      were receiving. Parents were more satisfied with their child's pain management
      and children received more analgesia when they were cared for by a lower grade
      nurse.

PMID- 12514484
TI  - Role of a paediatric nurse in primary care 1: research issues.
AB  - This study, which looked at the potential for the role of a paediatric nurse in
      primary care, was a tripartite partnership arrangement with Community Health
      Sheffield NHS Trust, the University of Sheffield and the Children's Hospital
      Sheffield. The study focused on the role and function of two qualified children's
      nurses each working within a different primary healthcare team (PHCT). It was
      important to allow the role to evolve without undue pressure, so that members of
      the PHCT could work with the nurses to establish what would be the most useful
      and relevant tasks to be carried out by the team. The methodological problems
      posed in this type of study where little was known about how a children's nurse
      would work in a PHCT resulted in exploring the concept of a formative evaluation
      process. The major data source and contribution to the evaluation were the
      nurses' reflective accounts of their role and function as members of the PHCT.
      Case studies written in the form of reflective diaries provided a self-critical
      approach to the record of tasks undertaken and explained why the service was
      taken up. Five constructions emerged: duplication and perceived threats to
      established nursing roles within the PHCT; improved care of children in PHCT
      settings; the nature of support for children and families; working as a nurse
      practitioner; and meeting unmet need. A clear need was demonstrated for a
      qualified children's nurse working in a community setting to raise the overall
      support and quality of care for a whole range of conditions which are currently
      low profile. There was evidence that these nurses met unmet need and were, at
      times, functioning as nurse practitioners and at times as advanced practitioners.
      This article, the first of two parts, focuses on the methods used and the
      associated problems. The second part will present the findings and discussions of
      the research.

PMID- 12514485
TI  - Spiritual coping mechanisms in chronically ill patients.
AB  - Addressing spiritual needs is acknowledged as an essential component of holistic
      nursing care. Findings are emerging that suggest that chronic illness demands
      significant changes in patients' lifestyle. In such circumstances it is claimed
      that spiritual care can be therapeutic to patients (Cohen et al, 2000; Sherwood,
      2000). This study was carried out in order to understand further the spiritual
      coping mechanisms of patients suffering from chronic illness. A qualitative
      methodology based on descriptive phenomenology was used to capture participants'
      lived experience. The main themes emerging from this study suggest that chronic
      illness led participants to use the following spiritual coping mechanisms: faith,
      prayer, and related sources of support. Patients coping with chronic illness were
      engaged in both a personal and private struggle. Patients may benefit from
      nursing interventions that are sensitive, supportive, and responsive to their
      spiritual needs.

PMID- 12514486
TI  - Clinical negligence and causation and remoteness of damage.
AB  - In this, the final article of this series on understanding negligence law, the
      causation and remoteness of damage is discussed. The final element that needs to
      be established in a negligence case is that the defendant's breach of duty was
      the cause of the claimant's loss and that this loss was not too far removed or
      remote from the actions of the defendant. The law involved in this area can be
      quite difficult to understand as some of the principles used are uncertain and
      the cases can be quite hard to draw together and reconcile.

PMID- 12514487
TI  - Why does modernization mean medicalization?

PMID- 12514488
TI  - Placing the right value on public servants.

PMID- 12514489
TI  - The distress experienced by people with type 2 diabetes.
AB  - With diabetes an ever-increasing problem across the developed world, a great deal
      of research has been carried out into the effects of the disease on the patient.
      Yet despite the fact that type 1 diabetes accounts for only a relatively small
      proportion of worldwide cases, it has been the focus of research attention. This
      study aimed to investigate the distress associated with type 2 diabetes, whether
      gender differences existed in the impact of type 2 diabetes and how men and women
      viewed dietary management. A multi-method, two-stage research approach was taken.
      Quantitative data were obtained using the Problem Areas in Diabetes (PAID)
      questionnaire, and no statistically significant gender difference was identified.
      Worrying about the future, the possibility of complications and feelings of guilt
      or anxiety when 'off-track' with diabetes management were sources of significant
      distress. Treatment mode, length of time diagnosed with diabetes and age were
      significant factors which impacted on the emotional distress experienced by the
      individual. A subsample of respondents took part in the survey. Behavioural
      impact, emotional impact and fear of complications were major themes identified
      in the interviews. Views of the dietary management of diabetes were also explored
      within the focus groups and three broad categories identified: dietary
      restrictions, value judgements and the influence of others. Awareness by health
      care professionals of factors influencing adaptation to diabetes is recommended.

PMID- 12514490
TI  - Innovations in district nursing: the use of a first dressing starter box.
AB  - Since the advent of nurse prescribing many district nurses have raised concerns
      about having only a simple non-adherent dressing available to apply to a wound
      while waiting for a prescription to be dispensed. This type of product does not
      meet the criteria for an ideal wound dressing. Using dressing products acquired
      from other sources, for example surplus dressings prescribed for another patient,
      is considered unacceptable clinical practice. This article describes a pilot
      study carried out to determine the feasibility of providing a 'starter box'
      filled with a selection of dressing products for use at the first dressing
      consultation. The results of the pilot study show that the availability of such a
      starter box could lead to a better wound care service for patients, and that cost
      savings could be made from avoiding unnecessary additional return visits or
      clinic appointments.

PMID- 12514491
TI  - Intermediate care rapid assessment support service: an evaluation.
AB  - This study evaluated a rapid assessment support service (RASS) in an inner city
      location. The evaluation focus was provided by the two main objectives of the
      service, i.e. to reduce the number of unnecessary emergency admissions for people
      over 65 years to acute hospitals and to support the assessment of people over 65
      years in their own homes. A case study design was employed and methods included
      documentary analysis of patients' discharge summaries and/or notes, patient/carer
      diaries and patient/carer storytelling. The most common reasons for referral, and
      goals identified following assessment, were mobility/falls prevention and
      hygiene/activities of living. The key themes identified concerning the assessment
      process were partnership working, promoting patient independence relief for
      carers, integration of health and social care assessment, effective use of health
      care professionals' time, integration with other services, satisfaction with the
      service and areas of dissatisfaction. Despite the methodological and practical
      limitations of this evaluation some of the early successes of this intermediate
      care service have been identified.

PMID- 12514492
TI  - Medicines management in care homes for older people: the nurse's role.
AB  - Increasing attention is being paid to the inappropriate use of medicines in UK
      care homes for older people. While polypharmacy may sometimes be necessary, older
      people can be particularly sensitive to the effects of medicines due to
      physiological chances, while the effect of a mixture of medicines is often
      unknown. The harmful consequences of inappropriate prescribing for older people
      unnecessarily add to overall health-care expenditure and the workload of staff.
      Community nurses can play an important role in attenuating some of these problems
      while enhancing the quality of life of older people in care homes. The growing
      population of older people and burgeoning health-care expenditure on medicines
      demands that greater attention is given to medicine management among older people
      so that the efficacy of therapeutic regimes are maximized.

PMID- 12514493
TI  - Does accident prevention education reduce the incidence of childhood accidents in
      the home?
AB  - This mini-review examines whether accident prevention education reduces the
      incidence of home accidents among children under the age of 5 years. The Cochrane
      Library, Medline, CINAHL and Embase databases were searched for randomized
      controlled studies (RCTs) and systematic reviews of RCTs that compared parents
      who received accident prevention education with those that did not. Only two RCTs
      met the inclusion criteria for analysis in this review. The results of these
      studies showed that there was no statistically significant difference in
      accidents between the two groups but the quality of the trials was low. An RCT in
      process (Watson et al, 2002) looks likely to provide evidence of a high standard,
      so that practice decisions regarding accident prevention education can be made.

PMID- 12514494
TI  - 'No change' is not an option.

PMID- 12514495
TI  - Divided by a common tongue: getting policy into practice.

PMID- 12514496
TI  - Exploring methods of wound debridement.
AB  - Dead tissue, in the form of slough and necrosis, can, if present in a wound,
      delay healing and promote infection. Debridement describes any method by which
      such materials are removed and, as a consequence, the potential to achieve wound
      healing enhanced. In this article, the first of two, the author discusses the
      history of debridement, cell death, the nature of necrotic tissue and a variety
      of debridement techniques. All methods of debridement have associated risks and
      benefits and while this article examines its clinical application there are also
      legal and professional issues to consider particularly in relation to
      conservative sharp debridement. These issues will be addressed in the second
      article.

PMID- 12514497
TI  - Pressure relieving equipment selection in the community: rising to the challenge.
AB  - Due to changes in health care provision district nurses are increasingly called
      on to assess for more specialized pieces of equipment from an ever-increasing
      choice of products. Eligibility criteria for the ordering of equipment have been
      developed in Leeds to assist district nurses in ensuring that the equipment they
      assess for is the most appropriate and suitable for its purpose and that it will
      be used safely and correctly. The use of the criteria is demonstrated through
      their application to pressure-relieving equipment. Use of the eligibility
      criteria will hopefully improve the overall quality of service for the patient
      and carers throughout the process of equipment provision, from assessment through
      to delivery and its subsequent use.

PMID- 12514498
TI  - Skin changes in the "at risk" foot and their treatment.
AB  - The skin provides a "mirror" of the patient's general health, and any changes
      from normal for that person may be generalized or located to specific body sites.
      In the foot, poor quality skin may develop associated with a number of medical
      disorders such as diabetes or rheumatoid arthritis, and peripheral states such as
      peripheral vascular disease. In these instances the foot is "at risk" of
      developing ulcers following even minor trauma. To manage epidermal and dermal
      changes efficiently, it helps to have a good understanding of the skin structure
      and function as well as knowledge of the more common conditions affecting the
      poorly viable foot. Skin physical characteristics change in the "at risk" foot
      and skin conditions and lesions, e.g. anhydrosis, fissures, ulceration, can
      develop readily and left untreated, there is increased morbidity and risk of
      mortality. Even apparently minor skin conditions in the foot are therefore worthy
      of attention and appropriate treatment as introduced in this paper, as all those
      involved in health care have a responsibility and role in foot health education.

PMID- 12514499
TI  - A national pilot to implement pressure ulcer guidelines: results of the baseline
      audit.
AB  - The Royal College of Nursing (RCN) national pilot audit project aims to
      facilitate the dissemination and implementation of the RCN clinical guideline on
      pressure ulcer risk assessment and prevention using an evidence-based, tailored
      strategy. Recent government White Papers reinforced the move towards evidence
      based healthcare that includes performance measures, clinical effectiveness and
      ongoing professional development. Structured dissemination and implementation of
      the RCN guideline can aid this process by improving patient care, as well as in a
      culture where more patients are seeking recompense for "poor" care assist in
      reducing litigation and complaints. This article focuses on the findings of the
      baseline audit. Providing a summary of the project to date, looking at site
      recruitment, the provisional results and recommendations of the baseline audit
      and local initiatives for supporting the ongoing implementation and the
      implementation resources developed to assist the sites in the process. The
      project is due for completion at the end of 2002 following which the final
      results will be published.

PMID- 12514501
TI  - [Gastrointestinal absorption of drugs through the digestive barrier].
AB  - Drug absorption through the digestive membranes occurs essentially by the
      paracellular route between the cells and through the tight junctions, and by the
      transcellular route via active or passive transfers across the membrane. Also,
      active transporters are able to pump substrates from the enterocytes back to the
      lumen via efflux proteins. These are able to slow and/or to reduce drug
      absorption, in particular, represent a source of variability by interactions with
      inducers or inhibitors such as pharmaceutical excipients. Other important factors
      are solubilization, drug metabolism, both in the lumen and in the enterocytes,
      gastric emptying and the interactions with food or between drugs.

PMID- 12514502
TI  - [Exchanges through the blood-brain barrier].
AB  - The blood-brain barrier (BBB) is the main interface controlling the exchange of
      nutrients and drugs between the blood and brain. Its specificity is given by some
      specific properties of the endothelium of the brain capillaries. They include the
      presence of tight junctions sealing adjacent endothelial cells and the absence of
      fenestrations preventing paracellular transport pathway across the BBB. The BBB
      is also a metabolic and pharmacological barrier because of the activity of many
      cytosolic enzymes and transporters expressed both or either at the luminal or
      abluminal faces of the brain microvessel endothelial cells. Macromolecules like
      insulin, leptin and transferrin may cross the BBB via receptor mediated
      transcytosis. More recently the discovery of P-glycoprotein, an ABC protein, at
      the luminal membrane of the brain endothelial cells has shown that several
      lipophilic antimitotic and psychotropic drugs are pumped out of the brain by this
      transporter. All these properties illustrate how complex the exchanges of
      nutrients and drugs across the BBB are.

PMID- 12514503
TI  - [Drug membrane transporters in the liver: regulation of their expression and
      activity].
AB  - Membrane transport proteins play a major role in hepato-biliary secretion of
      xenobiotics. Some of them, especially OATPs and OCT1, are present at the vascular
      pole of hepatocytes and mediate uptake of xenobiotics into parenchymal liver
      cells from blood whereas others, such as P-glycoprotein and MRP2, are ABC
      transporters present at the canalicular domain of hepatocytes and responsible for
      the transmembrane passage into bile of drugs or their metabolites. Many
      endogenous or exogenous factors, including drug metabolizing enzyme inducers,
      alter expression of hepatic transporters whose activity can moreover be inhibited
      by various structurally-unrelated compounds. Such changes of expression and/or
      activity of membrane transport proteins may contribute to some drug interactions.

PMID- 12514504
TI  - The Hydrogen-Bond: computational approaches and applications to drug design.
AB  - This mini-review begins with a presentation of the hydrogen-bond in the context
      of other intermolecular recognition forces of significance in molecular biology
      and molecular pharmacology. This is followed by a survey of the various
      computational methods available to calculate the hydrogen-bonding capacity of
      compounds. Such methods use quantum mechanics, molecular mechanics, or algorithms
      based on experimental fragmental values. A recent and promising advance in the
      computation of H-bonding capacity is the development of specific molecular
      interaction fields (MIFs) known as molecular hydrogen-bonding potentials (MHBPs).
      Their interest in relating molecular properties to pharmacokinetic behaviour is
      highlighted with two examples, namely oral drug absorption and blood-brain
      barrier permeation.

PMID- 12514505
TI  - [Conclusion].

PMID- 12514506
TI  - [Which species actually exist in relation with time and pH when compounds exhibit
      several dissociation and kinetic constants: the striking case of a thieno-1,4
      diazepine].
AB  - A solution of a molecule having several dissociation and kinetic constants
      evolves with time and pH-value. Now it is important from a pharmacological
      standpoint to know which species actually exist in solution. The knowledge of the
      kinetic and dissociation constants allows to plot the concentrations profiles
      versus time and versus pH-values of the whole protolytes. This is illustrated
      with a thieno-1,4-diazepine.

PMID- 12514507
TI  - [New substituted 4-thioxothiazolidin-2-one derivatives: synthesis and structural
      study].
AB  - Synthesis and physico-chemical properties of some 3-benzyl- and 3-phenacyl-4
      thioxo-5-benzylidenethiazolidin-2-one derivatives are described. Fifteen new
      compounds were synthesized from thiazolidin-2-one by thionation of the 4
      carbonyle, alkylation of the 3-N and aldolisation-crotonisation of 5-CH(2) with
      aromatic aldehydes. Soon, these new compounds will be tested for their
      bacteriostatic activity.

PMID- 12514508
TI  - [Evaluation of antifungal and mollusuicidial activities of Moroccan Zizyphus
      lotus (L.) Desf].
AB  - Zizyphus lotus (L.) Desf. is one of the traditional drugs commonly used in folk
      medicine in Morocco. Extracts obtained from the successive exhaustion in
      petroleum ether, chloroform, ethyl acetate and methanol were in vitro found
      active either against nine pathogenic fungi and Bulinus truncatus, the
      intermediate host and vector of transmission of unitary schistosomiasis in
      Morocco. Particularly, the chloroform extract appears the most interesting in
      antifungal tests at lowest concentrations because of its countenance on terpenic
      compounds. Whereas, methanolic extract was found to possess the strong
      mollusuicidial activity and exhibited potent "knock-down" effect on molluscans
      related to its countenance on saponins.

PMID- 12514509
TI  - [Mechanism of action of tetrahydro-N, N-dimethyl-5, 5-diphenyl-3
      furanemethanamine, a putative nootropic, anti-epileptic and antidepressant
      compound].
AB  - Pharmacological studies on tetrahydro-N, N-dimethyl-5, 5-diphenyl-3
      furanemethanamine (AE14) pointed out its prominent action in the passive
      avoidance test, its antagonist effect on electrogenic (maximal electroshock, MES)
      or pentetrazole-induced tonic convulsions, and its anti-immobility effect in the
      forced swim test (FST) in mice. These pharmacological data suggest that AE14
      could exhibit nootropic, antiepileptic and antidepressant actions. Molecular
      pharmacology studies (receptology, bioresponse) with AE14 showed a selective M1
      muscarinic agonism, one of the most potent currently known, and an affinity for
      site 2 of the sodium ion channels, at least as strong as those of first or second
      generation antiepileptics (phenytoin, lamotrigine). These molecular effects show
      that AE14 could be a potential second generation anti-Alzheimer drug, a third
      generation antiepileptic, and an adjunct for antidepressants.

PMID- 12514510
TI  - [Legislative framework of embryo research].
AB  - The French bioethics law promulgated in 1994 and still in force prohibits nearly
      all forms of research on the human embryo. However, the concept of the patient
      embryo developed in this discussion demonstrates that it is medically mandatory
      to proceed with such research. The project presented by the government in
      accordance with the obligatory revision of the 1994 law which was adopted by the
      Parliament in January 2002 accepts the principle of research on the embryo and
      embryo cells. An Agency for embryology, human reproduction, and human genetics
      (APEGH) will be in charge of controlling these activities.

PMID- 12514511
TI  - [Dermatology in France in 2000. What is the present and future?].

PMID- 12514512
TI  - [Notoriety of the French dermatology: analysis through dermatological
      publications].
AB  - INTRODUCTION: The aim of this study was to evaluate the publications of French
      dermatologists in medical journals. METHODS: All papers published in 1998 and
      indexed in PubMed were searched under the names of all dermatologists listed in a
      French registry of hospital dermatologists and analyzed. A sample of 8
      departments of dermatology in University hospitals was selected at random and the
      publications from these departments were compared to those from the departments
      of rheumatology in the same hospitals. In addition the publications of French,
      German and Italian dermatologists were compared for the years 1989, 1994 and
      1999. RESULTS AND CONCLUSION: In 1998, 452 papers were published by French
      dermatologists. This was more than for rheumatologists in the selected sample
      (133 vs 82). The impact factor was rather low (1.8 +/- 3), in part because many
      papers (43 p. 100) were written in French. In addition original studies and
      research papers accounted for only 20 p. 100 of all papers. The numbers of papers
      devoted to clinical research had increased in the last 10 years and compared
      favorably with German and Italian dermatology. In contrast, the number of
      research papers had decreased in the last 10 years in strong contrast with the
      dramatic increase of research papers originating from Germany.

PMID- 12514513
TI  - [Dermatology in private practice in France in 2000].
AB  - OBJECTIVES: Data regarding French dermatological practice are scarce. Our
      objective was to identify the skin disorders most commonly diagnosed by office
      based dermatologists. We also documented the severity of these skin disorders, as
      reflected by the repercussions on patient's everyday life, and the way physicians
      managed patients. DESIGN: We carried out a one-day survey of visits to a randomly
      selected sample of 900 French office-based dermatologists. The randomization was
      stratified according to the five French different dialing area codes. RESULTS:
      Office-based dermatologists saw 6411 patients with 7839 skin disorders during the
      survey. The daily number of visits to French dermatologists was estimated at 47
      000 and the annual number between 12 and 14 millions. Office-based dermatologists
      mostly managed warts, acne, nevus, dermatitis, malignancies and pre-malignancies,
      fungal infection and psoriasis. Repercussions on patients'everyday life were
      assessed by physicians as important or very important in 28 p. 100 of cases. Half
      of the patients received topical treatment, 20.5 p. 100 a systemic drug and 40 p.
      100 a minor surgical procedure (including cryotherapy). CONCLUSION: Although
      dermatologists frequently see benign skin disorders such as warts or nevus, more
      severe diseases represent an important part of their activity.

PMID- 12514514
TI  - [Survey on the activity of hospital departments of dermatology in France].
AB  - INTRODUCTION: The College des Enseignants de Dermatologie de France initiated a
      study to assess the activity of the departments of dermatology in French
      hospitals. We report the results of this survey. MATERIAL AND METHODS: The study
      was conducted during a randomly selected week in the year 2000. An anonymous
      questionnaire was sent to all the departments of dermatology in the hospitals in
      France and was completed for each patient leaving the hospital during that week.
      The data collected were: the type of establishment, admission method,
      hospitalization method, type of pathology, motive for hospitalization, length of
      hospitalization and type of treatment used. RESULTS: The response rate was of 96
      p. 100 for the University hospital centers and 80 p. 100 for the non-university
      hospitals. The number of patients treated per year was of 65 628 for the
      University hospitals and of 16,000 for the others. Ninety percent of the
      hospitalizations corresponded to direct admissions. The pathologies at the origin
      of the majority of yearly hospitalizations were, for the University hospitals:
      melanoma, leg ulcers, highly specialized dermatoses and systemic diseases and for
      the other hospitals: leg ulcers, HIV infection, highly specialized dermatoses and
      erysipela. The pathologies requiring the greatest number of hospitalization days
      were melanoma, leg ulcers, erysipela and highly specialized dermatoses.
      DISCUSSION: This study shows that the activity in the departments of dermatology
      is centered on pathologies that are clearly severe in terms of Public Health
      (oncology, infectious diseases and angiology). It also shows the efforts made for
      the management of patients in out-patient settings.

PMID- 12514515
TI  - [Abstract quality assessment of articles from the Annales de Dermatologie].
AB  - INTRODUCTION: Article's abstracts are an important part of the publication,
      widely available in electronic databases. We assessed the quality of abstracts in
      the Annales de Dermatologie. The main objective was to compare abstract quality
      in 3 periods in the past decade. In this Journal, structured abstracts are
      required since 1993. The secondary objective was to compare structured and non
      structured abstract quality. MATERIAL AND METHODS: Three periods were assessed:
      1991-92, 1996 and 2000. We selected the abstracts of original studies, excluding
      non focused descriptive case series. We used a criteria scale elaborated by
      Narine et al. Thirty criteria were assessed for each abstract, divided into 8
      categories: purpose, research design, setting, subjects, intervention, outcome
      measurement, results and conclusion. If applicable to the study, a criterion was
      rated 1 (present) or 0 (absent). The final score for each abstract was defined as
      the ratio of positive answers among rated criteria. Mean scores for each period
      were compared using analysis of variance (mean +/- standard deviation). The
      temporal trend was calculated by simple linear regression. The mean scores of
      structured and unstructured abstracts were also evaluated and then compared.
      RESULTS: For each period, chronologically, 8, 17 and 18 (total 43) abstracts were
      evaluated. Mean scores for each period were 0.72 +/- 0.20 (1991-92); 0.69 +/-
      0.12 (1996) and 0.83 +/- 0.08 (2000). These 3 scores were significantly different
      (P=0.006), with a trend toward increasing (Regression coefficient R(2)=0.136;
      P=0.015). Research setting obtained the lowest score (0.4). Structured (0.72 +/-
      0.20; n=35) and non structured abstracts (0.76 +/- 0.12; n=8) were not
      significantly different. DISCUSSION: Abstracts of articles published in the
      Annales de Dermatologie contained on average 3/4 of the required informative
      items. The trend toward better scores may be explained by an increased attention
      of the editorial board as well as authors and reviewers. The quality could be
      improved by systematically mentioning the research setting.

PMID- 12514516
TI  - [Hypohidrotic ectodermal dysplasias].
AB  - Ectodermal dysplasias form a heterogeneous group of hereditary diseases
      associating dysplastic abnormalities of four tissues which derive from the
      ectoderm. The frequency of these congenital diseases is estimated at 7 out of
      100,000 newborns. More than 150 different syndromes have been described. Solomon
      and Keuer, then Freire Maya and Pinheiro established a classification of these
      diseases dividing them in 6 groups depending on the presence of the four main
      clinical disorders: trichodysplasia, onychodysplasia, hypodontia and
      hypohidrosis. We focus on the fundamental clinical features of the hypohidrotic
      ectodermal dysplasias and propose an overview of the most frequent forms based on
      a review of the literature.

PMID- 12514517
TI  - [Bacterial cellulitis. Forms borderline between medical and surgical (3 cases)].
AB  - BACKGROUND: An acute infectious cellulitis may be managed medically (erysipelas
      or non-necrotizing infectious cellulitis) or surgically (necrotizing infectious
      cellulitis, necrotizing fasciitis). We report 3 cases of non-necrotizing
      infectious cellulitis borderline between medical and surgical forms, complicated
      by compartment syndrome, the surgical decompression of which permitted patients'
      cure. CASE REPORTS: Three patients, 27, 52 and 84 years old, were admitted for an
      acute infectious cellulitis of the leg. At admission, the leg area involved was
      erythematous, painful, indurated, with one or several bullae, purpura, pustules,
      hypoesthesia or limited skin necrosis, and no immediate need for surgical
      exploration. The clinical evolution was characterized by the slow appearance or
      extension of signs of severity, despite the modification in antibiotic treatment.
      Magnetic resonance imaging findings were indicative of a non-necrotizing
      infectious cellulitis in 2 patients. In one patient, necrotizing fasciitis could
      not be excluded. In all patients, surgical exploration showed an important
      quantity of non-purulent fluid between muscles and hypodermis, with no evidence
      of abscess or necrosis. A large incision rapidly cured all patients. DISCUSSION:
      These three observations were characterized by the initial signs of moderate
      severity and no response to an appropriate medical treatment, which led to
      surgical exploration. Surgery showed no abscess or necrosis but an important
      quantity of sterile fluid; it also permitted rapid cure of patients. These cases
      present a borderline form of infectious cellulitis, with severe local
      inflammation caused by a compartment syndrome. Surgical decompression was needed
      for cure. The potential value of magnetic resonance imaging in this situation
      should also be stressed.

PMID- 12514518
TI  - [Idiopathic hypereosinophilic syndrome and bullous pemphigoid].
AB  - BACKGROUND: We report the case of bullous pemphigoid associated with
      hypereosinophilic syndrome. This association has only been report only once in
      the literature. CASE REPORT: A 58 year-old man was admitted for a surinfected,
      pruriginous and generalized bullous dermatosis. Physical examination revealed
      bronchial rales. The cutaneous histology showed a junctional and intradermic
      cleavage associated with massive dermal infiltration by eosinophils. The
      diagnosis of a pemphigoid was confirmed by immunology. In parallel, the
      idiopathic hypereosinophilic syndrome was evoked in view of persisting
      hypereosinophilia without detected aetiology and associated with pulmonary
      infiltration. The skin lesions disappeared under symptomatic treatment, but the
      patient was rehospitalized 4 months later for severe relapse of dermatosis
      associated with medullary infiltration by eosinophils. Oral corticosteroid
      therapy gave spectacular results on both skin and blood formula. DISCUSSION: This
      association is rare, but seems to be related by the same immunological factors
      highlighting eosinophils. In addition, the presence of hypereosinophilic syndrome
      gives the pemphigoid some particular clinical, histological and evolutive
      characteristics.

PMID- 12514519
TI  - [Cutaneous drug eruption with two antihistaminic drugs of a same chemical family:
      cetirizine and hydroxyzine].
AB  - BACKGROUND: H1-antihistamines are widely used to relieve symptoms of allergic
      disorders. A few skins reactions to H1-antihistamines have been described in the
      literature. We report the first case of cutaneous drug eruption as fixed drug
      eruption with 2 antihistamines of the same chemical family: cetirizine and
      hydroxyzine. CASE REPORT: A 73 year-old man was admitted because of a third
      cutaneous eruption with the same morphologic features of the same sites as
      before. The first and second eruption appeared after 4 hours of cetirizine
      intake, the third eruption appeared after 4 hours of hydroxyzine intake. Healing
      was obtained after stopping the medication. Histology showed induced drug
      reaction. Patch tests with cetirizine and hydroxyzine were negative, except false
      positivity with dimethylsulfoxide vehicles. DISCUSSION: The diagnosis of
      cutaneous drug eruption as non pigmenting fixed drug eruption related to
      cetirizine and hydroxyzine was retained. Allergy to both H1 antihistamines can be
      explained by the fact that they've got the same chemical node that is piperazine,
      and by the fact that cetirizine is the main metabolite of hydroxyzine. Oral test
      provocation was omitted because the patient had already reexposed himself to the
      drugs. To identify the drug responsible for fixed drug eruption, peroral
      provocation tests are the most valuable method, but carry the risk of a strong
      reaction. Some authors use patch tests, but their positivity is inconstant. Their
      interest in fixed drug eruption is undergoing assessment.

PMID- 12514520
TI  - [Cutaneous vasculitis, myelodysplasia and relapsing polychondritis].
AB  - BACKGROUND: Relapsing polychondritis is a rare autoimmune disease, characterized
      by recurrent inflammation of cartilaginous tissues. In some cases, many other
      tissues can be involved. CASE REPORT: We describe the case of a 64 year-old man
      with relapsing polychondritis, whose first symptoms were papulonodular and
      mucosal aphthous lesions. The skin biopsy revealed vasculitis without
      leukocytoclasic features. The diagnostic of relapsing polychondritis was made
      only two years later, thanks to recurrent auricular chondritis. Since the
      beginning, the disease was associated with a myelodysplasia. DISCUSSION:
      Dermatological manifestations are noticed in less than 50 p. 100 of cases during
      the evolution of relapsing polychondritis. An association with a myelodysplasia
      has already been reported, and it could be a particular form of relapsing
      polychondritis. Myelodysplasic syndromes are more frequently associated with
      relapsing polychondritis than with other vasculitis. It must be sought especially
      when cutaneous and mucosal manifestations exist.

PMID- 12514521
TI  - [Septic embolism complicating an aorto-duodenal fistula].
AB  - INTRODUCTION: Aorto-duodenal fistulas are rare complications of aortal
      prostheses. We report a case revealed by septic embolism. OBSERVATION: A 63 year
      old man with past history of obliterating arteriopathy of the legs and bifemoral
      aortal bypass was hospitalized in a dermatology unit because of bilateral
      ecchymotic and purpural lesions of the soles of the feet and fever. Hemocultures
      were positive for E. coli and alpha hemolytic streptococci. The search for a deep
      infectious area was negative. Gastro-esophageal fibroscopy revealed an aorto
      duodenal fistula showing a fresh blood clot in the second duodenum. DISCUSSION:
      Aorto-duodenal fistulas are rare complications of aortal prostheses, the high
      mortality of which is often related to late diagnosis. The initial symptoms such
      as fever, abdominal pain, palpable mass and digestive bleeding are inconstant and
      the clinical profile polymorphous. Any suspicion of septic embolism in a patient
      with an aortal vascular prosthesis must lead to the search for prosthetic
      infection and an aorto-duodenal fistula, notably in the presence of osteomyelitis
      at distance from the prosthesis. A scan and/or scintigraphy with normal
      polynuclears do not eliminate the diagnosis of an aortal-duodenal fistula and a
      gastro-esophageal fibroscopy should be performed.

PMID- 12514522
TI  - [Bullous localization of a lupus erythematosus induced by radiotherapy].
AB  - INTRODUCTION: Connective diseases induced or exacerbated by radiotherapy are not
      frequent. We report a particular erosive erythematosus lupus with lesions in the
      precise distribution of radiation therapy given for a breast cancer. OBSERVATION:
      An 80 year-old woman presented with painful erosive skin lesions of her breast
      which had been treated by irradiation 9 years before. The patient also had
      rheumatoid arthritis. A skin biopsy showed keratinocyte necrosis, acantholysis
      and a dermal lymphocytic infiltrate under the basal cell layer. Direct
      immunofluorescence showed granular deposition of IgG, IgM and C3 along the basal
      cell layer. Antinuclear antibodies were positive at a titre of 1: 1,000.
      Erythematosus lupus diagnosis was established and annular lesions secondarily
      appeared on her neck, back, and arms. A treatment with hydroxychloroquine and
      topical corticosteroids was effective in 3 months. DISCUSSION: The unusual
      erosive lesions and their localization on a previously irradiated site suggest
      the role of X-rays in our observation, despite their late appearance after
      radiotherapy. Radiotherapy and erythematosus lupus affect the same target
      structures (basal cells and small dermal capillaries) and could have additive
      effects. The presence of rheumatoid arthritis in the past medical history may
      have exaggerated this complication.

PMID- 12514523
TI  - [Syphilis in patients without immunodeficiency: 5 cases].

PMID- 12514524
TI  - [Sub-ungual tumor of the thumb].

PMID- 12514525
TI  - [Multiple papules of the trunk].

PMID- 12514526
TI  - [Eyelids dermatoses].

PMID- 12514527
TI  - [Zoon's balanitis].

PMID- 12514528
TI  - [Hydrocolloid dressings].

PMID- 12514529
TI  - [The parotid duct].

PMID- 12514530
TI  - [Photodistributed hyperpigmentation with diltiazem].

PMID- 12514531
TI  - [Is laser depilation of a hairy nevus safe?].

PMID- 12514546
TI  - [Capsule Endoscope NORIKA System].

PMID- 12514547
TI  - [The present condition and the countermeasure against patient exposure in cardiac
      catheterization].

PMID- 12514548
TI  - [Apparatus engineering of X ray CT equipment (7): three-dimensional display].

PMID- 12514555
TI  - [Development of a computerized method for identifying view position and
      orientation for chest radiographs by using a template matching technique].
AB  - For implementation of computer-aided diagnostic systems for chest radiographs in
      the clinical environment, it is necessary to correctly identify two view
      positions [posteroanterior (PA) and lateral views] and four orientations (upward,
      downward, leftward, and rightward) for chest radiographs. In picture archiving
      and communication system (PACS), the information on the view position and
      orientation for chest radiographs is often not recorded or is recorded
      incorrectly. The purpose of this study was to develop a computerized method for
      correctly identifying view position and orientation for chest radiographs by
      using a template matching technique. Our basic approach is to find the most
      similar template to an unknown chest image by examining the similarity of the
      unknown chest image with a number of templates for PA and lateral views at the
      four image orientations, and to determine simultaneously the view position and
      orientation for the unknown chest image. All upward templates were produced from
      the PA or lateral images for upward orientation for various patient sizes. By
      rotating the upward templates, we produced the templates for downward, leftward,
      and rightward orientations. To evaluate the similarity of a test image with all
      templates, the cross-correlation values of the test image with all templates were
      obtained. The view position and image orientation for the unknown image was
      considered to be identical to those for the template with which the largest cross
      correlation value was obtained. Our results indicated that all cases of 200 PA
      and 200 lateral views were correctly identified in terms of the view position and
      image orientation.

PMID- 12514556
TI  - [Evaluation of image quality of breast phantom radiographs by fuzzy measure
      theory: cross grid and single grid].
AB  - Our study was carried out to compare and evaluate two types of grids (single and
      cross types) for the removal of scattered X-rays exclusive to mammography in an
      ACR-specified 156 model phantom using fuzzy measure theory (fuzzy measure and its
      fuzzy integration). When three simulated shadows of the breast phantom (fibrous,
      calcified, and tumor) were integrated, the cross grid (Gc) showed a slightly
      higher evaluation value than the single grid (Gs). In addition, when two shadows
      were combined or each shadow was alone, the Gc was evaluated as 2% or 3% higher.
      It is difficult to determine the physical properties of a grid for removal of
      scattered X-rays exclusive to the breast considering the structure of equipment,
      but if a visual and subjective evaluation is quantitatively conducted by applying
      fuzzy kinetics, comparison and evaluation can be carried out.

PMID- 12514557
TI  - [Application of the OS-EM method to myocardial SPECT: evaluation of artifact
      reduction using heart phantom with liver object].
AB  - SPECT images reconstructed by the ordered subsets expectation maximization (OS
      EM) method are known to have fewer artifacts induced by the nearly high-count
      background organs. The aim of this study was to determine whether the OS-EM
      method is effective in reducing artifacts induced by the high radioactivity of
      liver compared with the filtered back projection (FBP) method using a heart
      phantom with a liver object. Heart and liver phantoms were laid to overlap each
      other by 2 cm, and the liver/heart radioactivity (L/H) ratios were 0:1, 2:1, and
      6:1. Short axial images of cardiac SPECT were reconstructed by OS-EM and the
      filtered back projection (FBP) method, and counts profiles were obtained for both
      methods. In both methods of image reconstruction, artifactual higher counts in
      the inferior wall of the heart were observed as the L/H ratio increased. When
      compared with the L/H ratio of 0:1, the increase in relative counts of the L/H
      ratio of 2:1 in the inferior wall showed a similar value for both methods (OS-EM:
      +9.7%, FBP: +11.6%). With the L/H ratio of 6:1, the OS-EM method showed a lesser
      increase in relative counts of the inferior wall than with the FBP method (OS-EM:
      +24.5%, FBP: +38.9%). Moreover, the areas of increased counts were smaller. In
      conclusion, the OS-EM method was thought to be more useful than the FBP method in
      reducing the increase in artifactual counts caused by the high radioactivity of
      liver.

PMID- 12514558
TI  - [Construction of a common utilization system for medical images using a high
      speed cable network].
AB  - We constructed an Electronic Medical Record (EMR) and Picture Archiving and
      Communication System (PACS) in December 1999, and established a satellite clinic
      5 km away from the core hospital in November 2001. Both medical doctors and
      patients were exchanged between the two institutes. Because it was necessary for
      both institutes to use the same medical information and medical images, we re
      constructed both the PACS and EMR using high-speed cable network technology.

PMID- 12514559
TI  - [Availability and improvement of a vacuum-type immobilization device in pediatric
      CT].
AB  - The essential factors for an immobilization device in pediatric CT are 1) absence
      of artifacts, 2) safety, 3) no disturbance of the patient's sedation, and 4) ease
      of handling. We evaluated the suitability of a commercially available vacuum-type
      immobilization device designed for radiation therapy (Vac-Lok) that meets these
      requisites. There were no artifacts in scans of the water phantom. The device
      easily immobilized the patient, was quick to release, and was superior to
      previous immobilization systems, according to replies to a questionnaire
      administered to physicians, technologists, and nurses. Schedule delays were
      reduced by using this device to examine sedated patients (up to 1 year of age).
      Despite these advantages, the device was too small to immobilize both extremities
      together when examining older patients. In order to overcome this problem, we
      invented a special immobilization device for pediatric CT. The new device could
      be applied to taller patients, up to 85 cm in height(the average height of 2-year
      old infants), and was able to contribute to efficient utilization of the
      examination room.

PMID- 12514560
TI  - [Report based on Fiscal 2000 Diagnostic X-ray Equipment Questionnaire Survey
      (conditions of X-ray units and similar equipment)].
AB  - The X-ray Systems Study Group, in an attempt to determine the current status and
      changes in the state of X-ray equipment, reception systems, and equipment
      control, conducted investigational research by distributing a questionnaire
      survey to 400 facilities. The rate of recovery was 33%. The capacity of
      transformers has been increasing in spite of the three-phase 415 V decrease in
      the power supply of X-ray equipment. Among high-voltage generators, inverter-type
      X-ray equipment accounted for 81.3% of units. The ratio of the X-ray tube of a
      conventional rotational system to that of a high-speed rotational system was 1:3,
      and 54.9% had target angles of 12 . Many X-ray tubes had a heat capacity of less
      than 200-300 kHU. The body parts that had the shortest times on radiography were
      adult chest and pediatric chest. In many cases, the shortest time used was 10
      msec. Facilities in which the shortest time was less than 10 msec accounted for
      almost half of the total number. Facilities where the radiation dose of
      radiography had decreased showed 1/4 of the digitalization whole. Measurement was
      carried out when the equipment was bought in 94.9% of facilities, and measurement
      when the service contract was finished was done in 77.1% of the responding
      facilities.

PMID- 12514561
TI  - [Report based on fiscal 2000 diagnostic x-ray equipment questionnaire
      survey(conditions of radiography)].
AB  - X-ray equipment has seen advances in inverters and the digitalization of
      reception systems. The X-ray Systems Study Group, in order to examine changes in
      the conditions of radiography, including pediatric radiography, variations in
      shortest irradiation time, and standardization of the conditions of radiography,
      carried out investigative research using a questionnaire survey that was sent to
      400 facilities. The recovery rate was 33%. In terms of the reception system, half
      of the general radiography systems were using computed radiography (CR). Seventy
      percent of respondents used an intensifying screen and film(S EF)in stomach
      double-contrast radiography. About 80% used digital radiography (DR) and digital
      subtraction angiography (DSA) in aorta abdominalis angiography. At least 70% of
      high-voltage generators were of the inverter type. The conditions of radiography
      were not greatly influenced by changes in reception systems and X-ray equipment.
      Many pediatric radiographies were carried out by radiological technologists. We
      consider it useful to conduct such survey investigations.

PMID- 12514562
TI  - Improving breast cancer care.

PMID- 12514563
TI  - Clinical considerations in the management of individuals at risk for hereditary
      breast and ovarian cancer.
AB  - BACKGROUND: Hereditary predisposition to breast and ovarian cancer, most commonly
      due to germline mutations in BRCA1 and BRCA2, has been recognized for many years.
      The optimal clinical management of individuals with such a predisposition is not
      yet completely defined. METHODS: The current literature regarding the clinical
      management of individuals at risk for hereditary breast and ovarian cancer was
      reviewed. RESULTS: Women with germline BRCA1 or BRCA2 mutations are at
      substantially increased risk for breast and ovarian cancer, although the risks
      may not be as high as originally reported. Current surveillance options are
      restricted in their effectiveness by both host and tumor factors as well as
      limitations of the techniques. Surgical prevention options, while effective, may
      be complicated by physical or psychological morbidity. Nonsurgical prevention
      options are under development. CONCLUSIONS: The ability to define women as being
      at hereditary risk for breast and ovarian cancer facilitates the use of
      specialized surveillance and prevention strategies. Genetic testing, which plays
      a role in defining risk, requires careful pre- and post-test counseling to
      discuss the limitations of testing itself and available management strategies.

PMID- 12514564
TI  - Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant
      treatment for breast cancer.
AB  - BACKGROUND: The majority of women diagnosed with early-stage breast cancer have
      an excellent long-term prognosis, but many will undergo temporary or permanent
      chemotherapy-induced amenorrhea. METHODS: While breast cancer is more common in
      older women, about 1 in 200 women under the age of 40 is at risk to develop
      breast cancer. Many of these women benefit from chemotherapy but are afraid to
      risk the opportunity to bear children. The authors review the current studies on
      the impact of adjuvant chemotherapy on amenorrhea and fertility in women with
      breast cancer. RESULTS: The likelihood of amenorrhea is based on the specific
      adjuvant chemotherapy regimen administered and the age of the patient. Future
      childbirth is a viable option for women treated for breast cancer at an early
      stage. While the use of tamoxifen as a hormonal therapy in premenopausal breast
      cancer is now the standard of care, no conclusive data confirm the benefit of
      GnRH agonists in adjuvant therapy after treatment with chemotherapy followed by
      tamoxifen. CONCLUSIONS: As more women over the age of 35 consider pregnancy,
      fertility issues are becoming important areas of investigation for the adjuvant
      treatment of breast cancer. Whether chemotherapy-induced amenorrhea has a
      prognostic effect remains unclear, and further studies are warranted.

PMID- 12514565
TI  - Ductal lavage for breast cancer risk assessment.
AB  - BACKGROUND: Effective chemoprevention is available for breast cancer, but it is
      associated with the potential for life-threatening adverse events. Accurate
      identification of women facing increased risk of breast cancer is therefore
      essential. Atypical hyperplasia is a histopathologic pattern that has been
      consistently associated with an elevated future risk of breast cancer. METHODS:
      The literature was reviewed to assess the strength of the association between
      atypical hyperplasia and breast cancer. The rationale for developing a
      nonsurgical modality to document the presence of atypia is discussed. RESULTS:
      Ductal lavage identifies atypical hyperplasia by retrieving epithelial cells shed
      into the ductal system with a specially designed catheter. Women with clinical
      evidence of increased breast cancer risk may consider ductal lavage as a means of
      determining whether abnormal proliferative activity is occurring in their breasts
      at a given point in time from ducts yielding fluid. CONCLUSIONS: Ductal lavage is
      a minimally invasive procedure that facilitates the detection of atypia via
      retrieval of breast ductal fluid that can be evaluated cytologically. It can
      facilitate the selection of women who may benefit from breast cancer risk
      reduction intervention.

PMID- 12514566
TI  - The use of bisphosphonates in patients with breast cancer.
AB  - BACKGROUND: Bone is the most common site of breast cancer metastases. Skeletal
      metastases may be associated with harmful and painful events such as fractures,
      spinal cord compression, and hypercalcemia. By inhibiting osteoclasts and bone
      resorption, bisphosphonates can interrupt the process of bone destruction and
      decrease the risk of skeletal complications. METHODS: A review of the literature
      was undertaken regarding the use of bisphosphonates in breast cancer management,
      with particular attention to prospective, randomized clinical trials that have
      influenced the treatment of bone metastases. RESULTS: Large prospective,
      randomized trials have demonstrated that bisphosphonates are effective in
      reducing skeletal-related complications from metastatic breast cancer.
      CONCLUSIONS: For many patients with osseous lesions from breast cancer,
      bisphosphonate therapy is a useful intervention in managing their disease.
      Bisphosphonates are the treatment of choice for hypercalcemia of malignancy and
      bisphosphonates reduce the risk of pathologic fractures, spinal cord compromise,
      the need for radiation or surgery to bone, and bone pain.

PMID- 12514567
TI  - Aromatase inhibitors in breast cancer: an update.
AB  - BACKGROUND: Tamoxifen has been the endocrine treatment of choice for patients
      with breast cancer. The development of selective aromatase inhibitors has offered
      an alternative management approach for patients in whom a hormonal approach is
      indicated. METHODS: The authors reviewed reports in which aromatase inhibitors
      were compared with tamoxifen for the treatment of metastatic disease, as well as
      information pertinent to their use as adjuvant therapy. RESULTS: Both
      nonsteroidal (anastrozole and letrozole) and steroidal (exemestane) aromatase
      inhibitors for metastatic disease appear to provide superior efficacy and a
      better toxicity profile in first- and second-line treatment of metastatic disease
      than tamoxifen. Early results from the ATAC trial suggest anastrozole is superior
      to tamoxifen for disease-free survival, particularly in receptor-positive
      patients, and in reducing the incidence of contralateral breast cancer.
      CONCLUSIONS: Aromatase inhibitors have important roles in optimal management of
      postmenopausal patients with hormone-responsive metastases in both the adjuvant
      and advanced-disease settings.

PMID- 12514568
TI  - Trastuzumab use in breast cancer: clinical issues.
AB  - BACKGROUND: Overexpression of the epidermal growth factor 2 HER2 in breast cancer
      tissue is associated with shorter survival. Trastuzumab, a monoclonal antibody
      against HER2, can induce tumor responses when given alone and enhances the
      effectiveness of several chemotherapeutic agents. METHODS: The recent clinical
      data on outcomes regarding testing for HER2 overexpression and the tolerance,
      toxicity, and antitumor effects of trastuzumab are reviewed. RESULTS: Trastuzumab
      use is indicated either alone or with chemotherapy only in patients with IHC 3+
      or FISH+ test results and survival is prolonged in patients with metastatic
      disease. Cardiac toxicity differs from anthracycline cardiac toxicity and is
      often reversible. CONCLUSIONS: The safety and efficacy profile of trastuzumab in
      patients with metastatic disease has led to large-scale testing of addition of
      the intervention in the adjuvant setting.

PMID- 12514569
TI  - Catheter-related bloodstream infections, part I: pathogenesis, diagnosis, and
      management.

PMID- 12514571
TI  - Presidential address: the American Association for Vascular Surgery: a tradition
      of imagination, innovation, and change.

PMID- 12514572
TI  - Intrasac flow velocities predict sealing of type II endoleaks after endovascular
      abdominal aortic aneurysm repair.
AB  - PURPOSE: The purpose of this study was to determine whether intrasac spectral
      Doppler flow velocities can predict whether or not a type II endoleak will
      spontaneously seal and to relate intrasac flow to preoperative branch vessel
      anatomy. METHODS: Between October 1996 and June 2002, 265 patients with abdominal
      aortic aneurysms underwent endovascular repair. Patients with less than 24 months
      of follow-up and type I endoleaks were excluded. Type II endoleaks were confirmed
      with duplex scan and computed tomographic angiography. Two groups were
      identified: 14 patients with sealed endoleaks (<6 months) without intervention
      and 16 patients with persistent endoleaks greater than 6 months and without
      resolution. Spectral Doppler flow velocities were recorded from endoleaks within
      the aneurysm sac. RESULTS: The two groups were similar in age, demographics, and
      aneurysm morphology. The mean follow-up times were 29.9 +/- 7.9 months for sealed
      endoleaks and 30.2 +/- 8.6 months for persistent endoleaks (P = not significant).
      Spectral Doppler velocities were significantly lower in patients with sealed
      endoleaks compared with persistent endoleaks (75.5 +/- 78.8 cm/s versus 138.2 +/-
      36.2 cm/s; P <.01). Patients with sealed endoleaks and low (<100 cm/s) intrasac
      Doppler velocities had significantly fewer patent inferior mesenteric arteries
      (43% versus 81%; P <.01), a smaller inferior mesenteric artery (5.6 +/- 1.8 mm
      versus 7.2 +/- 1.3 mm; P <.01), and fewer paired lumbar arteries (1.3 +/- 0.8
      versus 2.4 +/- 0.6; P <.0001) compared with those with persistent endoleaks and
      high (>100 cm/s) intrasac flow velocities. Three patients with sealed endoleaks
      had Doppler velocities of 200 cm/s or greater. However, the diameter of the
      inferior mesenteric artery in these patients was 4 mm or less with no visualized
      lumbar arteries before surgery. Aneurysm diameter(-4.6 +/- 5.6 mm) and volume (
      0.9 +/- 45.2 mL) decreased in patients with sealed endoleaks. Aneurysm diameter
      (1.8 +/- 4.9 mm) and volume (18.5 +/- 33.9 mL) increased slightly in patients
      with persistent endoleaks (P <.05). No ruptures or conversions occurred in any
      patient. Secondary interventions to treat type II endoleaks were unsuccessful in
      six of 16 patients (38%) with persistent endoleaks. CONCLUSION: Intrasac Doppler
      velocities can be used to predict whether a type II endoleak will spontaneously
      seal. High-velocity type II endoleaks are related to preoperative large branch
      vessel diameter and number and are resistant to endovascular treatment.

PMID- 12514573
TI  - Mechanical failure of prosthetic human implants: a 10-year experience with aortic
      stent graft devices.
AB  - OBJECTIVE: The first endovascular stent graft was implanted to treat an abdominal
      aortic aneurysm more than a decade ago. This technique has evolved dramatically
      with the growing understanding of metallurgic and fabric sciences and improved
      device designs. However the potential for stent graft material failure remains.
      This investigation describes the incidence of material failure, potential modes
      of device fatigue, and the clinical significance of these failures. METHODS: Six
      hundred eighty-six endovascular stent grafts were used to treat patients with
      aortic aneurysms. Device fatigue in the form of stent, suture fracture, or graft
      wear was identified with an analysis of follow-up radiographs and explanted stent
      grafts. A review of patient clinical histories, spiral computed tomographic scan
      studies, scanning electron microscopy, and energy dispersion spectroscopy of
      explanted devices was conducted to evaluate the modes and consequences of
      failure. RESULTS: Sixty patients were identified with device fatigue, 49 of whom
      had abdominal endovascular repairs and 11 of whom had thoracic repairs. Of the 60
      patients with stent graft fatigue, 43 patients had metallic stent fractures, 14
      had suture disruptions, and three had graft holes. These material failures
      occurred within seven distinct stent graft designs. The average time to the
      recognition of failure was 19 months, with a mean follow-up period of 8 months
      since the event was identified. Eleven patients died, and one was lost to follow
      up 2 years after identification of a stent fracture. The remaining patients are
      presently being followed eoyj physical examination, plain film radiograph, and
      computed tomographic scans for clinical sequelae of device fatigue. CONCLUSION:
      Endovascular stent graft fatigue has been recognized in numerous devices after
      aortic implantation. Fatigue may take the form of stent, graft, or suture
      failure, with certain modes unique to specific stent graft devices. The clinical
      significance of stent graft material failure remains uncertain.

PMID- 12514574
TI  - The prevalence and natural history of aortic aneurysms in heart and abdominal
      organ transplant patients.
AB  - OBJECTIVE: The purpose of this study was to document the prevalence and clinical
      features of aortic aneurysms in heart and abdominal transplant patients. METHODS:
      We undertook a retrospective review of 1557 patients who had heart, liver, or
      kidney transplantation between January 1, 1987, and December 31, 2000. Aortic
      aneurysms were identified by computed tomographic scan, ultrasound scan, or at
      the time of surgery for rupture. An aortic diameter of 3.5 cm was used as the
      threshold for the definition of aneurysmal disease. We compared dichotomous
      variables with Fisher's exact test and continuous variables with the Wilcoxon
      rank-sum test. RESULTS: There were 296 heart, 450 liver, and 811 kidney
      transplants performed on adult patients during the study period. We identified 18
      transplant patients who had an aortic aneurysm (13 heart, three liver, two
      kidney). Seven patients (41%) had rupture of the aortic aneurysm, and five of
      these patients died. There were no deaths from causes other than aortic aneurysm
      rupture. The rate of aneurysm rupture was 22.5% per year. Eight patients had the
      aortic aneurysm repaired electively with no deaths and no hospital stay greater
      than 15 days. The mean aortic aneurysm size at rupture was 6.02 +/- 0.86 cm, and
      the smallest aneurysm that ruptured was 5.1 cm. The pretransplant rate of aortic
      aneurysm expansion was 0.46 cm/y, but this increased to 1.00 cm/y after
      transplantation (P =.08). The rate of aortic aneurysm expansion among heart
      transplant patients and abdominal transplant patients was the same (P =.51). The
      prevalence of aortic aneurysm was 4.1% in cardiac transplant patients and 0.4% in
      abdominal transplant patients. Earlier in our series (1987 to 1996), 11% of the
      cardiac transplant patients were screened for aortic aneurysms, and the
      prevalence rate of diagnosis was 3.0%. Screening of cardiac transplant candidates
      became more frequent in 1997 (87% screened), with an associated increase in the
      aortic aneurysm prevalence rate to 5.8% in the patients who were screened.
      CONCLUSION: Aortic aneurysms in cardiac and abdominal transplant patients have an
      aggressive natural history with high expansion and rupture rates. Screening
      transplant patients for aortic aneurysms will increase detection and facilitate
      elective repair, which is generally well tolerated. These findings support
      programs for early detection and elective treatment of aortic aneurysms in organ
      transplant patients, particularly those having heart transplants.

PMID- 12514575
TI  - Multistate population-based outcomes of combined carotid endarterectomy and
      coronary artery bypass.
AB  - OBJECTIVES: The management of combined carotid and coronary disease is
      controversial, and the outcomes of combined carotid endarterectomy (CEA) and
      coronary artery bypass grafting (CABG) have not been determined on a community
      wide basis. This study was undertaken to evaluate the community-wide outcomes of
      combined CEA and CABG and to evaluate the risk for adverse events. METHODS: A
      complete medical record review of 10,561 CEA procedures randomly selected from
      Medicare patients undergoing CEA in 10 states was performed. In this sample, 226
      procedures were performed in combination with CABG in the same operative event.
      RESULTS: Recent ipsilateral stroke or transient ischemic attack was the
      indication for the CEA in only 12% of patients undergoing CEA/CABG, and 56% were
      asymptomatic with respect to the carotid lesion. The combined stroke and death
      rate was 17.7% (25 nonfatal strokes, two fatal strokes, and 13 nonstroke deaths).
      Eighty percent of the nonfatal strokes were disabling. Proximal aortic arch
      atherosclerosis and symptomatic carotid stenosis were associated with stroke (P
      <.05). Female gender, emergent operation, redo CABG, blood pressure on pump,
      total pump time, presence of left main disease, and number of diseased coronaries
      were associated with mortality (P <.05). The strokes appeared to be associated
      with the operative event, but diagnosis was delayed and postevent carotid patency
      was not documented. Most strokes were not limited to the hemisphere ipsilateral
      to the CEA. CONCLUSION: The community-wide outcomes of combined CEA/CABG in the
      Medicare population are inferior to those reported in many single-institution
      reviews. Diagnosis of postoperative stroke is often delayed, and most strokes are
      not limited to the hemisphere ipsilateral to the CEA operative site.

PMID- 12514576
TI  - High-risk carotid endarterectomy: fact or fiction.
AB  - OBJECTIVE: It has been proposed that patients whose conditions do not meet North
      American Symptomatic Carotid Endarterectomy Trial inclusion criteria or have
      anatomic risk factors constitute a "high-risk" group for carotid endarterectomy
      (CEA) and might be candidates for primary carotid angioplasty stenting. Our
      objective was to review a consecutive series of isolated CEAs, identify the
      number of such patients at high risk, and determine whether their operations were
      associated with increased complication rate. METHODS: Consecutive isolated CEAs
      performed between June 1996 and June 2001 were reviewed. High-risk comorbidities
      included: age 80 years or more (n = 80), New York Heart Association class III/IV
      angina (n = 16), Canadian class III/IV heart failure (n = 4), myocardial infarct
      6 months or less (n = 11), steroid-dependent or oxygen-dependent pulmonary
      disease (n = 4), and creatinine level of 3 or more (n = 13). Anatomic high risk
      was defined by: contralateral occlusion (n = 66), lesion above C(2) or
      requirement of digastric division (n = 53), reoperation (n = 29), and neck
      radiation (n = 3). Statistical analysis was with chi(2) analysis. RESULTS: Of 788
      patients reviewed, 228 (29%) were classified as high risk by one or more of the
      previous criteria (63% comorbidity, 28% anatomy, 9% both). Presence of
      preoperative neurologic symptoms and postoperative results were similar across
      all patient groups. The total stroke and death rate was 1.1% for all the
      patients. Six patients had postoperative strokes (0.8%), and three patients died
      of myocardial infarcts (0.4%). The stroke and death rate was 1.3% in the high
      risk group as compared with 1.1% in the normal-risk group (P =.51). CONCLUSION:
      The concept of the high-risk CEA must be critically reexamined. Although 29% of
      patients for CEA were high risk as defined by others, we found no evidence that
      this influenced the results after CEA. Patients with significant medical
      comorbidities, contralateral carotid occlusion, and high carotid lesions can
      undergo operation without increased complications. If a high-risk group exists,
      it is small and restricted to reoperation or radiated neck (4% in this series).
      With this possible exception, carotid angioplasty stenting should be restricted
      to randomized clinical trials.

PMID- 12514577
TI  - Modifiable patient factors are associated with reverse vein graft occlusion in
      the era of duplex scan surveillance.
AB  - OBJECTIVE: Modifiable patient factors that contribute to graft occlusion may be
      addressed after surgery. To determine risk factors associated with reverse vein
      graft (RVG) occlusion, we examined the characteristics and duplex scan
      surveillance (DS) patterns of patients with RVGs. METHODS: Patients treated with
      RVG from January 1996 through December 2000 were identified from a prospective
      registry. The study population consisted of all patients with RVGs performed
      during the study period with grafts that subsequently occluded. Patients whose
      grafts remained patent served as age-matched and gender-matched control subjects.
      The prescribed DS regimen was every 3 months for the first postoperative year and
      every 6 months thereafter. Early DS failure was defined as having no DS within
      the first 3 months. Cox proportional hazards analysis was used to compare the two
      groups. Hazard ratios were calculated. RESULTS: During the study period, 674
      patients underwent RVG. Fifty-five patients with occluded RVGs were compared with
      118 with patent RVGs. The follow-up period for occluded grafts was 13.40 +/-
      12.59 months and for patent grafts was 32.40 +/- 15.61 months. Dialysis therapy,
      a known hypercoagulable state, continued smoking, and DS failure were independent
      factors associated with RVG occlusion. The hazards ratio for dialysis was 6.45
      (95% CI, 3.07 to 13.51; P <.001), for current smoking was 4.72 (95% CI, 2.5 to
      8.85; P <.001), for hypercoagulable state was 2.99 (95% CI, 1.47 to 6.10; P
      =.003), and for early DS failure was 2.43 (95% CI, 1.29 to 4.59; P =.006).
      CONCLUSION: Continued smoking and failure to undergo DS within the first three
      postoperative months are modifiable factors associated with RVG occlusion.
      Smoking cessation and graft surveillance must be stressed to optimize patency of
      infrainguinal RVGs.

PMID- 12514578
TI  - Postoperative duplex scan surveillance of axillofemoral bypass grafts.
AB  - OBJECTIVE: Duplex scan surveillance (DS) for axillofemoral bypass grafts (AxFBGs)
      has not been extensively studied. The intent of this study was twofold: 1, to
      characterize the flow velocities within AxFBGs; and 2, to determine whether
      postoperative DS is useful in assessment of future patency of AxFBGs. METHODS: We
      identified all patients who underwent AxFBG procedures between January 1996 and
      January 2001 at our combined university and Veterans Affairs hospital vascular
      surgical service. All grafts were performed with ringed 8-mm
      polytetrafluoroethylene with the distal limb of the axillofemoral component
      anastomosed to the hood of the femoral-femoral graft. DS was every 3 months for 1
      year and every 6 months thereafter. Duplex scan results were compared in
      primarily patent grafts with grafts that thrombosed. Graft failures from
      infection were excluded. Influences of ankle-brachial index, blood pressure,
      outflow patency, operative indication, and comorbidities on graft patency were
      analyzed. RESULTS: One hundred twenty patients underwent AxFBG procedures. Twenty
      eight were excluded because of infection or death before surveillance
      examination. Fourteen were lost to follow-up, 23 had failed grafts from
      occlusion, and 55 had grafts that remained patent. In the 78 patients evaluated
      during long-term follow-up period, the mean peak systolic velocities (PSVs) at
      the proximal (axillary) anastomosis during the first postoperative year ranged
      from 153 to 194 cm/s. Mean PSVs at the mid portion of the axillofemoral graft
      during the first postoperative year ranged from 100 to 125 cm/s, whereas those
      for the distal axillofemoral anastomosis ranged from 93 to 129 cm/s. Mean
      midgraft and distal anastomotic velocities obtained before thrombosis were
      significantly lower in the thrombosed grafts compared with the last recorded
      velocities at the same sites in the patent grafts (mean PSV, 84 versus 112 cm/s;
      P =.015; mean PSV, 89 versus 127 cm/s; P =.024, respectively). Forty-eight
      percent of occluded grafts had a mean midgraft PSV at last observation of less
      than 80 cm/s. Blood pressure correlated with midgraft velocity (r = 0.415; P
      <.05). With multivariate logistic regression analysis, a mean midgraft velocity
      less than 80 cm/s was the sole independent factor associated with graft failure
      (P <.01). No patients with midgraft velocities greater than 155 cm/s had
      occlusion. CONCLUSION: Flow velocity varies widely within and among AxFBGs.
      Patency of AxFBGs is associated with higher midgraft PSV, and thrombosis with
      midgraft velocities less than 80 cm/s.

PMID- 12514579
TI  - Lower extremity stepping-table magnetic resonance angiography with multilevel
      contrast timing and segmented contrast infusion.
AB  - OBJECTIVES: Standard lower extremity contrast-enhanced magnetic resonance
      angiography (LE-CEMRA) with single injection bolus-chase methods on the basis of
      a single pelvis timing run can be accurate for depicting most vascular occlusive
      lesions but may fall short of catheter-based angiography when imaging tibial and
      pedal vessels. Magnetic resonance angiography techniques with a second contrast
      timing bolus and separate acquisitions for the calves and the pelvis greatly
      improve reliability and reduce venous contamination to levels that may render
      conventional angiography obsolete. METHODS: From July to December 2001, 60
      consecutive patients underwent LE-CEMRA of the calves with separate stepping
      table acquisitions of the pelvis and thighs. Forty-five (75%) had complete or
      partial angiographic correlation during an endoluminal intervention or operative
      completion study. Lower extremity vessels were divided into anatomic segments
      (aortoiliac, femoropopliteal, tibial-pedal) for review. Three blinded observers
      assessed magnetic resonance source partitions, maximum-intensity projections, and
      volume-rendered images. Disease per segment was graded from insignificant (<20%)
      to occluded (100%) in 10% increments. Segments were also scored for venous
      contamination (scale, 0 to 3) and diagnostic quality (scale, 1 to 5). Digital
      subtraction angiograms were assessed similarly but separately. RESULTS: The
      combination dual-timing/dual-injection technique had an overall sensitivity,
      specificity, and accuracy of 99%, 97%, and 98%. Venous contamination and artifact
      were virtually eliminated with combined technique LE-CEMRA. Diagnostic quality of
      calf and foot vessels was significantly superior to conventional bolus-chase
      magnetic resonance techniques (P <.01). CONCLUSION: Hybrid dual-acquisition LE
      CEMRA allows complete timing specification that consistently produces high
      quality, artifact-free images of the calf and pedal vessels. These techniques may
      be accurate enough to replace conventional digital subtraction angiogram for
      evaluation of lower extremity vascular occlusive disease.

PMID- 12514580
TI  - Outcome of catheter-directed thrombolysis for lower extremity arterial bypass
      occlusion.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical outcome of
      patients undergoing catheter-directed thrombolysis (CDT) for lower extremity
      arterial bypass (LEAB) occlusion. METHODS: A retrospective review was performed
      of two university-based practices from 1988 to 2001. All patients with LEAB
      occlusion (<14 days by history) undergoing CDT as initial treatment were
      included. Technical success, complications, secondary patency, and limb salvage
      were examined. Additional analysis examined secondary procedures performed for
      residual lesions or failed CDT and the number of LEABs that were replaced or that
      became infected. RESULTS: One hundred four patients (77% male; mean age, 65
      years) had 109 LEAB occlusions. CDT restored patency in 77%. Of the 25 LEABs that
      failed initial CDT, 15 underwent surgical thrombectomy/revision, four were
      replaced, and six underwent no further interventions. Of the 84 LEABs
      successfully lysed, 51 had residual lesions that underwent revision with
      interventional (n = 30) or surgical (n = 15) techniques or both (n = 6). Median
      hospital stay was 8 days with three periprocedural deaths. One quarter of CDT
      procedures had bleeding or thrombotic complications or both. The mean follow-up
      period was 45 months. Secondary patency rates on an intention-to-treat basis
      (attempted thrombolysis) were 32% and 19% at 1 and 5 years, respectively. After
      successful CDT, the 1-year secondary patency rate was comparable in LEABs with or
      without residual lesions (42% versus 45%). Overall, the limb salvage rates were
      73% and 55% at 1 and 5 years, respectively. The survival rate was 56% at 5 years.
      Ten of the 54 LEABs (19%) that eventually failed after successful CDT had three
      or more reocclusive episodes. Seven LEABs (8.3%) salvaged with CDT eventually
      became infected from recurrent interventions; six of these necessitated major
      amputation. Twenty LEABs initially salvaged with CDT were replaced (four
      immediately and 16 after episodes of recurrent ischemia). Two patients died
      during hospitalization for treatment of recurrent ischemia. CONCLUSION: Despite
      relatively high initial technical success for LEAB thrombolysis, eventual failure
      is the rule rather than the exception. Recurrent LEAB occlusions lead to
      significant morbidity, including recurrent interventions, eventual graft
      infection/replacement, and limb loss. However, LEAB replacement has substantial
      problems associated with limited conduit, reoperative anatomy, and subsequent
      wound complications. We therefore advocate an initial attempt at CDT with liberal
      use of graft replacement for early and late failures or as an initial strategy in
      those with favorable remaining conduit.

PMID- 12514581
TI  - Does severe venous insufficiency have a different etiology in the morbidly obese?
      Is it venous?
AB  - OBJECTIVE: Chronic venous insufficiency (CVI) is the most common cause of leg
      ulcers. Patients with morbid obesity are remarkable for particularly recalcitrant
      ulcers. Because obesity is not specifically incorporated in CEAP or other venous
      scoring systems, we sought to characterize this group of patients more
      completely. METHODS: Patients with severe CVI (CEAP clinical class, 4, 5, and 6),
      and class III obesity (body mass index [BMI], >40) were reviewed. Findings from
      clinical and duplex ultrasound scan (DU) examinations were compared with the CEAP
      classification, its adjunctive venous clinical severity score, and sensory
      thresholds. RESULTS: A review of clinic records identified 20 ambulatory patients
      with a mean age of 62 years, a mean BMI of 52, and a mean weight of 164 kg (361
      lbs); all but one had bilateral symptoms. No evidence of venous insufficiency was
      detected with DU in 24 of the 39 limbs. Although some valvular incompetence was
      detected with DU in 15 of 39 limbs, these abnormalities were widely dispersed
      between 28 sites; eight limbs had findings at only one site. Ulceration (mean
      area, 29 cm(2)) was present in 25 limbs and necessitated 7 months for healing; 13
      (52%) recurred at least once during a mean observation period of 36 months. The
      mean sensory threshold of 5.21 exceeded current risk thresholds used in diabetic
      screening programs. The distribution of CEAP clinical class was C4 (n = 14), C5
      (n = 14), and C6 (n = 11). Increasing CEAP class correlated with an increased
      mean BMI of 47, 52, and 56, respectively (P <.01). CEAP also correlated with a
      rising mean venous clinical severity score of 10, 11, and 15, respectively (P
      <.05). CONCLUSION: Patients with class III obesity had severe limb symptoms,
      typical of CVI, but approximately two thirds of the limbs had no anatomic
      evidence of venous disease. The association of increasing limb symptoms with
      increasing obesity suggested that the obesity itself contributes to the
      morbidity.

PMID- 12514582
TI  - Endoluminal repair of abdominal aortic aneurysm prevents enlargement of the
      proximal neck: a 9-year life-table and 5-year longitudinal study.
AB  - OBJECTIVE: Endoluminal repair of abdominal aortic aneurysm (AAA) is predicated on
      stability of the proximal neck of the aneurysm. Reports on morphologic changes in
      the proximal neck after endoluminal repair of AAA have thus far been limited in
      duration to 3 years or less. The aim of this study was to document changes in
      diameter of the proximal neck of AAA in a group of patients who had undergone
      endoluminal repair between 5 and 9 years previously. METHODS: Between May 1992
      and December 1996, 61 patients with AAA were treated with endoluminal repair by
      the senior author. The following patients were excluded from the study group:
      those requiring primary conversion to open repair at the original operation (n =
      8), those with false aneurysm (n = 1), and those with dissection in the proximal
      neck (n = 1). Fifty-one patients (48 men and three women) with a mean age of 71
      years remained in the study group. The endoprostheses used were modified Parodi
      (n = 4), Endovascular Technologies (n = 14), White-Yu (n = 10), Stentor/Vanguard
      (n = 21), and Bard 1996 prototype (n = 2). Morphologic changes in the proximal
      aortic neck were studied with contrast computed tomographic scan with the
      methodology recommended by the Ad Hoc Committee for Standardized Reporting
      Practices for Endovascular AAA Repair (revised version). The maximum transverse
      diameter of the proximal neck was measured 1 cm below the most inferior renal
      artery. A Kaplan-Meier analysis was performed showing the proportion of patients
      at risk with a demonstrated enlargement of the neck at each interval of time
      compared with the predischarge computed tomographic scan. A longitudinal study of
      morphologic changes in the proximal aortic neck was also undertaken in 28
      patients with successful endoluminal repair who survived 5 years. RESULTS: The
      Kaplan-Meier curve showed a probability of no dilatation of the proximal neck of
      0.943 at 7 years after endoluminal AAA repair. Of 28 patients with 5 years of
      follow-up after discharge, only two had increases in the diameter of the proximal
      neck greater than 2 mm. The endograft in both patients had undergone migration
      before any proximal neck dilation. A paired t test showed that the overall
      average increase of 0.4 mm (standard error, 0.3 mm) in these 28 patients was not
      statistically significant (P =.23). CONCLUSION: A high probability (0.943 at 7
      years) exists of no enlargement of the proximal neck of AAA after endoluminal
      repair. We hypothesize that endografts positioned correctly immediately below the
      renal arteries protect the proximal neck from dilatation in a manner that does
      not occur after open repair of AAA.

PMID- 12514583
TI  - Endovascular treatment in diseases of the descending thoracic aorta: 6-year
      results of a single center.
AB  - OBJECTIVE: The purpose of this study was to evaluate endovascular treatment in
      diseases of the descending thoracic aorta. MATERIAL AND METHODS: This study was
      designed as a single center's (university hospital) experience. Over a 6-year
      period (1995 to 2001), thoracic endografts were placed in 74 patients with a
      diseased descending thoracic aorta who were at high risk for conventional open
      surgical repair: 34 had atherosclerotic aneurysms, six had posttraumatic
      aneurysms, 14 had type B dissection with aneurysmal dilatation of the false
      lumen, 12 had isthmic transections from blunt trauma, five had thoracoabdominal
      aneurysms (treated with a combined procedure), two had aortic coarctation, and
      one had an aortobronchial fistula. Twenty-six procedures (35.1%) were conducted
      as emergencies, and 48 (64.9%) were elective. The feasibility of endovascular
      treatment and sizing of stent grafts were determined with preoperative spiral
      computed tomography and intraoperative angiography. RESULTS: Endovascular
      operations were completed successfully in all 74 patients; postprocedural
      conversion to open repair was necessary in three cases. The overall 30-day
      mortality rate was 9.5% (seven deaths). Temporary neurologic deficits developed
      in two patients; not one patient had permanent paraplegia. The primary endoleak
      rate was 20.3% (15 patients). The mean follow-up period was 22 months (range, 3
      to 72 months). Five deaths occurred in the follow-up period, and three patients
      needed secondary conversion to open repair 2, 3, and 14 months after initial
      endografting. CONCLUSION: Endoluminal treatment in diseases of the thoracic
      descending aorta is feasible and may offer results as good as the open method.

PMID- 12514584
TI  - Acute and contained rupture of the descending thoracic aorta: treatment with
      endovascular stent grafts.
AB  - PURPOSE: The purpose of this study was to evaluate feasibility and safety of
      endovascular stent grafting for the treatment of patients with rupture of the
      descending thoracic aorta. METHODS: Thirteen patients with rupture of the
      descending thoracic aorta were treated with endovascular stent grafting. Six
      patients were treated on the day of diagnosis because their vital signs were
      unstable, and the other seven patients were treated electively. Five patients had
      infection or potential infection, and the other eight patients did not. Expanded
      polytetrafluoroethylene-covered or polyester-covered Z stents were used in all
      patients. RESULTS: Stent grafts were successfully placed in all patients. No
      endoleaks were observed at the end of the procedure. However, rebleeding was
      observed within 2 weeks of the procedure in two patients with infection. Six
      patients (46%) died within 5 months of the procedure (mean survival period, 61 +/
      60 days). All five patients with infection (100%) died, and only one of eight
      patients without infection (13%) died (P <.01). The remaining seven patients are
      alive during the mean follow-up period of 21 months (overall survival rate, 54%),
      although additional surgical interventions, including surgical conversion in one
      case and upper extremity extraanatomic bypass in the other, were necessary in two
      of these patients. CONCLUSION: Endovascular stent grafting may be a safe and
      feasible method for the treatment of rupture of the descending thoracic aorta in
      selected patients without infection. However, its usefulness in terms of long
      term prognosis appears to be extremely limited, especially in patients with
      infection.

PMID- 12514585
TI  - Conformational changes associated with proximal seal zone failure in abdominal
      aortic endografts.
AB  - OBJECTIVE: Endovascular aneurysm repair (EVAR) has become a popular treatment for
      abdominal aortic aneurysm (AAA). This study examines conformational changes in
      the infrarenal aortas of patients in whom proximal seal zone failures (PSF)
      developed after EVAR. METHODS: All 189 patients with aortic endograft underwent
      routine post-EVAR computed tomographic scan surveillance. Patients identified
      with proximal type I endoleaks, type III endoleaks, or proximal component
      separation without demonstrable endoleak underwent three-dimensional
      reconstruction of the computed tomographic scans from which measurements of the
      migration, length, volume, and angulation of the infrarenal aorta were made.
      RESULTS: Five patients (3%) had PSF develop, four of whom had aortic extender
      cuffs. Although changes in the AAA volume and aortic neck angle were slight or
      variable, the mean AAA length increased 34 mm and the mean aortic body angulation
      increased 17 degrees (P =.03 and.01, respectively). Lengthening and migration
      caused proximal component separation in four patients, with concomitant migration
      in two patients. Two patients underwent endovascular repair, two patients needed
      explantation of the endograft, and one patient awaits endovascular repair.
      Proximal component separation and type III endoleak recurred in one patient and
      were repaired with a custom-fitted graft. CONCLUSION: PSF of aortic endografts is
      associated with proximal angulation and lengthening of the infrarenal aorta.
      These findings reinforce the importance of proper initial deployment to minimize
      the need for aortic extender cuffs, which pose a risk of late endoleak
      development.

PMID- 12514586
TI  - The relationship between aortic wall distensibility and rupture of infrarenal
      abdominal aortic aneurysm.
AB  - OBJECTIVE: A more accurate means of prediction of abdominal aortic aneurysm (AAA)
      rupture would improve the clinical and cost effectiveness of prophylactic repair.
      The purpose of this study was to determine whether AAA wall distensibility can be
      used to predict time to rupture independently of other recognized risk factors.
      METHODS: A prospective, six-center study of 210 patients with AAA in whom blood
      pressure (BP), maximum AAA diameter (Dmax), and AAA distensibility (pressure
      strain elastic modulus [Ep] and stiffness [beta]) were measured at 6 months with
      an ultrasound scan-based echo-tracking technique. A stepwise, time-dependent, Cox
      proportional hazards model was used to determine the effect on time to rupture of
      age, gender, BP, Dmax, BP, Ep, beta, and change in Dmax, Ep, and beta adjusted
      for time between follow-up visits. RESULTS: Median (interquartile range) AAA
      diameter was 48 mm (41 to 54 mm), median age was 72 years (68 to 77 years), and
      median follow-up period was 19 months (9 to 30 months). In the Cox model, female
      gender (hazards ratio [HR], 2.78; 95% CI, 1.23 to 6.28; P =.014), larger Dmax
      (HR, 1.36 for 10% increase in Dmax; 95% CI, 1.12 to 1.66; P =.002), higher
      diastolic BP (HR, 1.13 for 10% increase in BP; 95% CI, 1.13 to 1.92; P =.004),
      and a decrease in Ep (increase in distensibility) over time (HR, 1.38 for 10%
      decrease in Ep over 6 months; 95% CI, 1.08 to 1.78; P =.010) significantly
      reduced the time to rupture (had a shorter time to rupture). CONCLUSION: Women
      have a shorter time to AAA rupture. The measurement of AAA distensibility,
      diastolic BP, and diameter may provide a more accurate assessment of rupture risk
      than diameter alone.

PMID- 12514587
TI  - Comparison of abdominal aortic hemodynamics between men and women at rest and
      during lower limb exercise.
AB  - INTRODUCTION: Biologic variations between men and women have been hypothesized to
      contribute to the differences in atherosclerosis epidemiology of the two genders.
      Hemodynamics are also hypothesized to play an important role in the localization
      of atherosclerosis in the abdominal aorta. However, the hemodynamics of men and
      women have not been compared at this location at rest or during lower limb
      exercise conditions. METHODS: A magnetic resonance-compatible exercise bicycle,
      magnetic resonance imaging techniques, and custom data processing software were
      used to quantify blood flow rate, wall shear stress, and oscillations in flow and
      wall shear stress at the supraceliac and infrarenal levels of the abdominal aorta
      of young healthy men and women at rest and during lower limb exercise. RESULTS:
      Heart rate increased from 73 +/- 6.2 bpm at rest to 110 +/- 8.8 bpm during
      exercise (P <.0001). No statistical differences were found at the infrarenal
      level for mean blood flow rate (men, 0.9 +/- 0.4 L/min; women, 0.8 +/- 0.4 L/min)
      or mean wall shear stress (men, 1.2 +/- 0.5 dynes/cm(2); women, 1.4 +/- 0.7
      dynes/cm(2)) at rest or mean blood flow rate (men, 5.9 +/- 1.3 L/min; women, 5.2
      +/- 0.8 L/min) or mean wall shear stress (men, 5.1 +/- 0.8 dynes/cm(2); women,
      5.4 +/- 2.1 dynes/cm(2)) during exercise. Also, no differences were seen in
      temporal flow and wall shear stress oscillations between men and women at rest or
      during exercise. Similarly, no significant hemodynamic differences were found
      between the genders at the supraceliac level. CONCLUSION: These similarities
      suggest that hemodynamics may not play a significant role in abdominal aortic
      disease differentiation between the genders and that biologic factors may be more
      important.

PMID- 12514588
TI  - Endoscopic transthoracic sympathectomy for upper limb hyperhidrosis: limited
      sympathectomy does not reduce postoperative compensatory sweating.
AB  - OBJECTIVE: Compensatory sweating is the most common and troublesome complication
      of thoracodorsal sympathectomy. Whether the magnitude of compensatory sweating is
      related to the extent of sympathectomy is unclear. We investigated the
      association between the extent of sympathectomy and the occurrence and severity
      of compensatory sweating after endoscopic transthoracic sympathectomy for upper
      limb hyperhidrosis. METHODS: From September 1992 to June 2000, data from patients
      undergoing thoracoscopic sympathectomy to treat primary upper limb hyperhidrosis
      in our department were prospectively collected. Routine follow-up with clinical
      examination was performed at 1, 3, and 6 months for the first postoperative year
      and every year thereafter. Late follow-up (February 2001) was with a standardized
      questionnaire by mail or telephone concerning compensatory sweating and patient
      satisfaction. Associations between the extent of sympathectomy and the occurrence
      and severity of compensatory sweating were analyzed with logistic regression and
      adjusted for age, gender, and relevant confounding factors. RESULTS: Two hundred
      sixty-eight sympathectomies were consecutively performed in 134 patients (99
      female, 35 male; mean age, 27.8 +/- 6.7 years). In the 84 patients with palmar
      hyperhidrosis, eight underwent T1-T2 resection, four T1-T3 resection, eight T2-T3
      resection, and 64 T2-T4 resection. In the 43 patients with palmar and axillary
      hyperhidrosis, eight underwent T1-T5 resection and 35 T2-T5 resection. The seven
      patients with isolated axillary hyperhidrosis underwent T3-T5 sympathectomy. No
      deaths occurred; one conversion for bleeding, one permanent Horner's syndrome,
      and six minor complications did occur. The initial cure rate was 99.2%. The
      initial satisfaction rate was 97%. The mean follow-up period was 44.3 months
      (range, 7 to 100 months), and complete follow-up was available in 132 patients
      (98.5%). Ninety-five patients (71.9%) had compensatory sweating develop. Seventy
      patients (53%) judged their compensatory sweating to be minor and intermittent,
      and 25 patients (19%) judged it severe (16% embarrassing, 3% disabling). On
      univariate and multivariate analysis, the extent of denervation was not
      associated with the occurrence or the severity of compensatory sweating. The late
      satisfaction rate was 91.5%. Compensatory sweating and temporary
      relief/recurrence were equally considered to be the main causes of
      dissatisfaction. CONCLUSION: Compensatory sweating was the most common long-term
      complication of thoracodorsal sympathectomy for primary hyperhidrosis. Its
      incidence and severity were not associated with the extent of sympathectomy.

PMID- 12514589
TI  - The "C" of CEAP: suggested definitions and refinements: an International Union of
      Phlebology conference of experts.

PMID- 12514590
TI  - Urine hemosiderin: a novel marker to assess the severity of chronic venous
      disease.
AB  - OBJECTIVE: Impaired venous drainage in severe chronic venous insufficiency (CVI)
      leads to microcirculatory overload, characterized by erythrocyte diapedesis and
      subsequent extravascular hemolysis, resulting in typical dermal hemosiderin
      deposition. We hypothesized that hemosiderin, normally absent, could be present
      in the urine in CVI. METHODS: The three-phase study included 117 patients with
      CVI and 12 healthy control subjects, all of whom had undergone clinical
      examination and duplex scanning. In phase 1, current methods were used to test
      urine for hemosiderin in 61 persons: 12 healthy control subjects, 24 patients
      with mild CVI (clinical class C1 to C3), and 25 patients with severe CVI
      (clinical class C4 to C6). In phase 2, the concentration of urinary hemosiderin
      was determined in 45 consecutive patients with CVI, CEAP class 1 to 6. A score of
      0 was assigned when typical hemosiderin granules were absent at microscopic
      examination, a score of 1 when one to three granules per field were detected; 2
      when four to six granules were detected; and 3 when more than six granules were
      observed. Phase 3 included 23 patients with CVI (clinical class 2 to 6).
      Hemosiderin concentration was determined and a score assigned before patients
      underwent surgical procedures to correct primary CVI. Both hemosiderin testing
      and duplex scanning were repeated after 6 months. RESULTS: Phase 1: Urine
      hemosiderin testing to determine presence or absence of CVI in patients with
      reflux detectable at duplex scanning yielded the following values: positive
      predictive value, 96% (95% confidence interval [CI], 86% to 100%); negative
      predictive value, 88% (CI, 68% to 97%); sensitivity, 94% (CI, 72% to 99%);
      specificity, 91% (CI, 83% to 99%); and diagnostic accuracy, 95% (CI, 86% to 99%).
      Phase 2: Hemosiderinuria score enabled classification of clinical severity of
      CVI. Mean scores, respectively, were clinical class 1, 0.18 +/- 0.12; class 2,
      0.75 +/- 0.47; class 3, 1.67 +/- 0.21; class 4, 1.86 +/- 0.26; class 5, 2.50 +/-
      0.28; and class 6, 1.92 +/- 0.21 (P <.001). Phase 3: At 6-month follow-up,
      hemosiderin score was improved, from 2.48 +/- 0.12 preoperatively to 0.78 +/-
      0.18 postoperatively (P <.0001). A score of 0 or 1 was associated with successful
      surgery, whereas a score of 2 or 3 reflected persistence of reflux. CONCLUSIONS:
      Determination of presence of hemosiderin in the urine is a new, sensitive, cost
      effective, noninvasive, and repeatable test that enables detection of substantial
      microcirculatory overload in patients with CVI.

PMID- 12514591
TI  - Hemodynamic effect of intermittent pneumatic compression and the position of the
      body.
AB  - PURPOSE: The purpose of this study was to investigate the three likely mechanisms
      of intermittent pneumatic compression (IPC) in deep vein thrombosis prophylaxis
      (increased volume flow, increased flow velocity, and acceleration of flow) and to
      do this in a variety of positions, in different venous segments, and with the
      stimulus of three different compression garments. METHODS: In 12 healthy
      volunteers, three types of compression cuffs were used: foot, calf, and calf +
      thigh. The foot was compressed with 80 mm Hg, and the calf and thigh with 40 mm
      Hg. Duplex ultrasound scan was performed before and during the compression in the
      horizontal, 15-degree head-down, and 15-degree head-up positions. The common
      femoral, greater saphenous, profunda femoral, superficial femoral, and popliteal
      veins were examined. RESULTS: In comparison with the horizontal position, the 15
      degree head-down position was associated with an increase of volume flow and
      velocities and the head-up position was associated with decreased flow and
      velocities in the deep veins. The application of IPC caused significant increases
      in velocities and volume flow in all venous segments. The lowest increase in
      velocities and volume flow in the deep veins was observed with the subjects in
      the head-down position, and in the two other positions, the increases were
      greater and similar to each other. IPC caused a much more prominent increase in
      flow velocities and volume flow in deep veins compared with simple elevation of
      the legs. CONCLUSION: IPC produces significant increases of venous flow volume
      and flow velocity and acceleration of flow. This is true whether the limbs are
      elevated, horizontal, or dependent. Segmental flow changes vary with the position
      of the patient and the compression garment used. Foot compression increases
      volume flow and velocity primarily in the popliteal vein. Calf compression
      provides maximal increases of volume flow and flow velocity through the deep
      veins.

PMID- 12514592
TI  - Evaluation of 4-mm to 7-mm versus 6-mm prosthetic brachial-antecubital forearm
      loop access for hemodialysis: results of a randomized multicenter clinical trial.
AB  - OBJECTIVE: Prosthetic arteriovenous fistulas for hemodialysis vascular access
      have a high incidence rate of thrombotic occlusions that result in graft failure.
      This randomized multicenter study was performed to assess the patency rates and
      the effect of 4-mm to 7-mm grafts on the development of stenoses. METHODS: A
      total of 109 patients who needed vascular access for hemodialysis were randomized
      to receive either 6-mm (n = 57) or 4-mm to 7-mm prosthetic brachial-antecubital
      forearm loop accesses (polytetrafluoroethylene). Duplex scanning, with
      measurement of blood flow and peak systolic velocity and detection of stenoses
      (>50%), was performed at 1, 6, and 12 months after surgery. Clinical data were
      obtained in a prospective manner and primary, assisted primary, and secondary
      patency rates were calculated with the Kaplan-Meier life-table analysis.
      Statistical analysis was performed with the independent samples t test and chi(2)
      test. RESULTS: At 1 year, patency rates were similar for both 4-mm to 7-mm and 6
      mm prostheses (primary, 46% versus 43%; assisted primary, 62% versus 58%;
      secondary, 87% versus 91%). The incidence rate of thrombotic occlusion was
      comparable for both groups (0.74/patient-year versus 0.88/patient-year; P >.05).
      Mean graft flow at 1, 6, and 12 months was 1416 versus 1415 mL/min, 1345 versus
      1319 mL/min, and 1595 versus 1265 mL/min (P >.05) for 4-mm to 7-mm and 6-mm
      grafts, respectively. Also, no differences in peak systolic velocities in any
      part of the grafts were observed. The percentage of stenoses detected was equal
      in both groups at 1 year after surgery (27% versus 20%; P >.05). CONCLUSION: A 4
      mm to 7-mm tapered prosthetic brachial-antecubital forearm loop access did not
      reduce the incidence rates of stenoses and thrombotic occlusions compared with a
      6-mm prosthetic conduit. Moreover, no differences in patency rates were observed.
      Therefore, we believe that the 4-mm to 7-mm graft should not be used routinely
      for hemodialysis vascular access.

PMID- 12514593
TI  - Vein versus polytetrafluoroethylene in above-knee femoropopliteal bypass
      grafting: five-year results of a randomized controlled trial.
AB  - OBJECTIVE: Controversy still exists whether polytetrafluoroethylene is equivalent
      to vein as bypass graft material for the above-knee femoropopliteal bypass.
      Therefore, a prospective randomized trial was performed to compare vein with
      polytetrafluoroethylene for femoropopliteal bypasses with the distal anastomosis
      above the knee. METHODS: Between January 1993 and December 1996, 151 above-knee
      femoropopliteal bypasses were performed. The indications for operation were
      severe claudication in 120 cases, rest pain in 20 cases, and ulceration in 11
      cases. After randomization, 75 reversed saphenous venous bypasses and 76
      polytetrafluoroethylene bypasses were performed. RESULTS: No perioperative
      mortality was seen, and 5% of the patients had minor infections of the wound, not
      resulting in loss of the bypass, the limb, or life. After 5 years, 38% of the
      patients had died and 7% were lost to follow-up. Only once was the saphenous vein
      necessary for coronary artery bypass grafting. Primary patency rates after 5
      years were 75.6% for venous bypass grafts and 51.9% for polytetrafluoroethylene
      grafts (P =.035). Secondary patency rates were 79.7% for vein and 57.2% for
      polytetrafluoroethylene bypasses (P =.036). In the venous group, 14 bypasses
      failed, leading to five new bypasses. In the polytetrafluoroethylene group, 29
      bypasses failed, leading to 16 reinterventions. For these 16 new bypasses, in
      four cases, the ipsilateral preserved saphenous vein was used. In both groups,
      one above-knee amputation and one below-knee amputation had to be performed.
      CONCLUSION: We conclude after 5 years of follow-up of this randomized controlled
      trial that a bypass with saphenous vein has better patency rates at all intervals
      and needs fewer reoperations. Saphenous vein should be the graft material of
      choice for above-knee femoropopliteal bypasses and should not be preserved for
      reinterventions. Polytetrafluoroethylene is an acceptable alternative if the
      saphenous vein is not available.

PMID- 12514594
TI  - Protective effect of prostaglandin E1 against ischemia of spinal cord during
      aortic cross clamping.
AB  - PURPOSE: The purpose of this study was to investigate whether or not 5-minute
      segmental intraaortic perfusion of prostaglandin E1 (PGE1) in the preischemic
      period has a protective effect against spinal cord ischemia during aortic cross
      clamping. METHODS: The rabbits were divided into two groups. In group A (n = 6),
      the infrarenal aorta was segmentally cross clamped and the segment was perfused
      for 5 minutes with blood and saline solution at first. The aorta was kept cross
      clamped without perfusion for a subsequent 20 minutes. In group B (n = 6), the
      infrarenal aorta was segmentally cross clamped and the segment was perfused for 5
      minutes with blood and saline solution containing PGE1 of 100 ng/kg/min at first.
      The aorta was kept cross clamped without perfusion for a subsequent 20 minutes.
      After the aorta was declamped, the experimental animals recovered from the
      anesthesia. Twenty-four and 48 hours after the operation, the hind limb function
      was estimated with Tarlov's grade. Then, the animals were killed for pathologic
      study. RESULTS: The systolic arterial pressures measured at the left common
      carotid artery through the experiment were not significantly different between
      the two groups. The perfusion of the aortic segment between the proximal and
      distal clamp was nonpulsatile. The perfusion pressures of the aortic segments at
      5 minutes after aortic cross clamping were 29 +/- 6 mm Hg and 33 +/- 6 mm Hg in
      groups A and B, respectively. No significant differences were seen between the
      two groups. In group A, the hind limb functions evaluated with Tarlov's grade
      after 24 hours and 48 hours were 0 to 3 (1.5 +/- 1.4) and 0 to 3 (1.3 +/- 1.4),
      respectively. In group B, these were 3 to 4 (3.5 +/- 0.5) and 3 to 4 (3.7 +/-
      0.5), respectively. A significant difference was seen between the two groups (P
      <.05). In the ventral horn of the L5, L6, and L7 segments, large motor neurons
      that seemed viable were more preserved in group B than in group A. CONCLUSION:
      Segmental intraaortic perfusion of PGE1 in the preischemic period reduced
      neurologic damage of spinal cord ischemia.

PMID- 12514595
TI  - Fluid flow regulates E-selectin protein levels in human endothelial cells by
      inhibiting translation.
AB  - OBJECTIVE: The purpose of this study was to determine the mechanism with which
      fluid flow inhibits endothelial E-selectin expression. METHODS: Cultured human
      umbilical vein endothelial cells were stimulated with inflammatory agonists
      (tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta, oncostatin M, or
      phorbol ester) in the presence or absence of fluid flow (peak shear stress,
      approximately 12 dynes/cm(2)) imposed with an orbital shaker. E-selectin
      expression was assessed with ribonuclease protection assay, immunoblotting,
      enzyme-linked immunosorbent assay, or metabolic labeling as appropriate. RESULTS:
      All agonists caused human umbilical vein endothelial cells to express E-selectin
      protein. Fluid flow inhibited E-selectin protein levels by about 50% in response
      to TNF-alpha but had no effect on total E-selectin messenger RNA (mRNA)
      expression. Flow inhibited E-selectin protein production even after initiation of
      E-selectin transcription. Flow did not cause E-selectin to be shed from the cell
      surface nor was E-selectin degradation accelerated. Although fluid flow did not
      reduce total cellular E-selectin mRNA levels in response to TNF-alpha, the amount
      of E-selectin mRNA present in the actively translated polysome fraction was
      markedly attenuated. CONCLUSION: These findings indicate that E-selectin
      expression is subject to translational and transcriptional control. Fluid
      mechanical forces can regulate endothelial phenotype by targeting translational
      control points.

PMID- 12514596
TI  - Local treatment of Dacron patch graft contaminated with Staphylococcus aureus
      with antibiotic-releasing porous apatite ceramic: an experimental study in the
      rabbit.
AB  - OBJECTIVE: The purpose of this study was to investigate whether or not infection
      of prosthetic vascular graft could be prevented with the placement of antibiotic
      loaded porous apatite ceramic on the graft with bacterial contamination. METHODS:
      Teicoplanin as an antibiotic was loaded into a beta-tricalcium phosphate (TCP)
      block of porous apatite ceramic. The activity of teicoplanin released from
      teicoplanin-loaded TCP was examined for 40 days at 2-day intervals. In an in vivo
      study, the graft was patched in the abdominal aorta of a rabbit. Two different
      doses of Staphylococcus aureus were applied (n = 13). Teicoplanin-loaded TCP was
      placed around the graft infected with S aureus (n = 6). The graft, the tissue
      around it, and the arterial blood were collected and cultivated 4 weeks after
      operation. RESULTS: The activity of teicoplanin in the replaced saline solution
      was maintained for at least 40 days. Because graft infection was established in
      all rabbits with a dose of 2 x 10(7) colony forming units, this dose was used as
      the dose of S aureus in this study. Fifty-seven percent of the subjects died from
      the infection. When teicoplanin-loaded TCP was placed around the graft
      contaminated with S aureus, no rabbits died. Bacterial cultures of the graft and
      of tissues around it were negative in all rabbits killed 4 weeks after operation.
      This infection was prevented with teicoplanin-loaded TCP in all rabbits.
      CONCLUSION: Teicoplanin-loaded TCP may be useful in avoiding Dacron graft
      infection with S aureus in rabbits.

PMID- 12514597
TI  - Transluminal stent graft repair with Wallgraft endoprosthesis in a porcine
      arteriovenous graft pseudoaneurysm model.
AB  - PURPOSE: Pseudoaneurysm is a known complication of arteriovenous grafts in
      chronic hemodialysis and can result in graft disruption or thrombosis if left
      untreated. This study evaluated the safety and efficacy of endovascular repair
      with Wallgraft endoprosthesis (Boston Scientific, Inc, Watertown, Mass) in a
      porcine arteriovenous graft (AVG) pseudoaneurysm model. MATERIALS AND METHODS:
      Bilateral groin AVG pseudoaneurysms (n = 18) were created with an oversized
      Dacron interposition graft within a polytetrafluoroethylene femoral AVG in nine
      domestic swine and allowed to mature 28 +/- 4 days (standard deviation).
      Transluminal placement of Wallgraft was performed to exclude the pseudoaneurysm
      from the AVG circulation. Hemodialysis was performed (400 mL/min x 1 hour, with
      intravenous heparin 30 units/kg) every 4 days for a total of 6 weeks via 15-gauge
      needles in the treated AVG pseudoaneurysm site. Arteriography and duplex
      ultrasound scan were performed to determine AVG patency and pseudoaneurysm flow.
      Histologic evaluation was performed to determine Wallgraft morphology. In vitro
      pulsatile flow chamber was used to determine maximal flow volume without peri
      Wallgraft endoleak. RESULTS: All AVG pseudoaneurysms were successfully excluded
      with the Wallgrafts. Twelve AVG (67%) remained patent at the completion of the
      study. No Wallgraft migration occurred from hemodialysis. Transient peri
      Wallgraft endoleak (<2 hours after hemodialysis) was present in 13 of 18 (72%)
      and four of 12 (33%) AVG pseudoaneurysms by weeks 1 and 6, respectively. With
      maintenance of an intraluminal pressure of 80, 100, 120, 140, and 160 mm Hg in
      the pulsatile flow chamber, the maximal flow rates without peri-Wallgraft
      endoleak were 625 +/- 120, 650 +/- 145, 620 +/- 95, 425 +/- 110, and 262 +/- 86
      mL/min. Scanning electron microscopy showed a neointimal layer covered with
      thrombus on the Wallgraft surface. CONCLUSION: Endoluminal placement of Wallgraft
      endoprosthesis provides adequate structural support for continuous hemodialysis
      after AVG pseudoaneurysm exclusion. Transient blood flow in the pseudoaneurysm
      cavity may occur immediately after the hemodialysis, which may represent the
      effect of heparin used during hemodialysis. This study suggests Wallgraft is a
      safe and effective treatment for AVG pseudoaneurysm and permits continuous
      hemodialysis.

PMID- 12514598
TI  - Shear stress magnitude and directionality modulate growth factor gene expression
      in preconditioned vascular endothelial cells.
AB  - OBJECTIVE: The purpose of this study was to simultaneously monitor the
      transcriptional levels of 12 endothelial growth factor genes in response to
      alterations in wall shear stress (WSS) under conditions relevant to the
      development of intimal hyperplasia, a major cause of arterial bypass graft
      failure. METHODS: Human umbilical vein endothelial cells were preconditioned in
      vitro under steady flow (WSS, 15 dynes/cm(2)) for 24 hours before being subjected
      to WSS at 25 (Delta = +10), 15 (Delta = 0), 5 (Delta = -10), 2.5 (Delta = -12.5),
      and 0 (Delta = -15) dynes/cm(2) or low magnitude WSS reversal (-2.5 dynes/cm(2))
      for 6 hours. A focused complementary DNA array was used to simultaneously measure
      messenger RNA expression levels for END1, endothelial nitric oxide synthase
      (NOS3), platelet-derived growth factor A, platelet-derived growth factor B
      (PDGFB), acidic fibroblast growth factor, basic fibroblast growth factor,
      transforming growth factor-alpha, transforming growth factor-beta, vascular
      endothelial growth factor, insulin-like growth factor-1, epidermal growth factor,
      and angiotensin converting enzyme. RESULTS: Preconditioning significantly (P
      <.05) increased the fold expression of NOS3 (4.1 +/- 1.4), basic fibroblast
      growth factor (3.90 +/- 1.16), vascular endothelial growth factor (3.39 +/-
      1.04), and insulin-like growth factor-1 (2.8 +/- 0.7) but decreased END1 (0.47 +/
      0.05) and PDGFB (0.70 +/- 0.04) messenger RNA expression levels relative to no
      flow controls, an effect that was sustained on removal from flow for 6 hours.
      Notably, the ratio of END1/NOS3 expression was diminished (0.11 +/- 0.03)
      relative to that of cells maintained in static culture. Although few differences
      in gene expression from baseline (15 dynes/cm(2)) were measured in cells exposed
      to either constant (Delta = 0) or step decreases (Delta = -10, -12.5, or -15
      dynes/cm(2)) in WSS, marked changes were seen in the group exposed to a step
      increase in WSS (Delta = +10) or to WSS reversal. Low magnitude retrograde WSS
      evoked significant (P <.05) transcriptional changes in multiple genes, including
      elevated END1 (4.1 +/- 0.5), platelet-derived growth factor A (1.5 +/- 0.2),
      PDGFB (2.3 +/- 0.3), and transforming growth factor-beta (1.5 +/- 0.2) levels,
      but depressed NOS3 (0.60 +/- 0.17) levels, and a marked increase in END1/NOS3
      (6.7 +/- 1.6) when compared with equal magnitude antegrade WSS (2.5 dynes/cm(2)).
      CONCLUSION: These results support the implementation of a preconditioning phase
      for in vitro WSS studies to establish a physiologic baseline. Our findings
      complement previous macroscale findings and are consistent with a cellular
      mechanism involving increased END1 and PDGFB levels, but decreased NOS3 levels,
      leading to intimal hyperplasia at regions of low magnitude reversing WSS.

PMID- 12514599
TI  - Totally videoendoscopic descending thoracic aorta to femoral artery bypass.
AB  - Descending thoracic aorta to femoral artery bypass is an effective and safe
      procedure for the treatment of aortoiliac occlusive disease when an approach to
      the abdominal aorta is undesirable. The major limitation of this technique has
      resulted from the morbidity rate associated with thoracotomy in a relatively high
      risk vascular surgery population. As a minimally invasive procedure,
      videoendoscopy has been shown to improve the patient postoperative course and
      comfort in the field of general and thoracic surgery. The same benefits could be
      expected from a videoendoscopic surgery involving the thoracic aorta. We report
      what we think to be the first totally videoendoscopic descending thoracic aorta
      to femoral artery bypass.

PMID- 12514600
TI  - Thrombin injection for failed stent graft repair of perforated atherosclerotic
      aortic ulcer.
AB  - We used direct thrombin injection to occlude a pseudoaneurysm that formed from a
      contained rupture of a penetrating atherosclerotic ulcer at the junction of the
      thoracic and abdominal aorta after we failed to seal the perforation with an
      endovascular stent graft. The principles of thrombin injection and the technical
      modifications specific for use in a false aneurysm of aortic origin are
      described. An evolving role for thrombin in endovascular therapy is suggested.

PMID- 12514601
TI  - Lumbar paraspinal rhabdomyolysis and compartment syndrome after abdominal aortic
      aneurysm repair.
AB  - Lumbar paraspinal compartment syndrome is an extremely uncommon condition that is
      known to occur after strainful exercise or trauma. We report on the original case
      of a 55-year-old man in whom lumbar paraspinal rhabdomyolysis and compartment
      syndrome developed after open abdominal aortic aneurysm repair, documented with
      technetium Tc(99m) bone scan and computed tomographic imaging, and in whom
      successful complete recovery was achieved with conservative management. Clinical
      features, pathophysiology, and diagnostic and therapeutic strategies of this
      unusual adverse event are discussed.

PMID- 12514602
TI  - Mesenchymal chondrosarcoma originating from the femoral vein.
AB  - Mesenchymal chondrosarcoma is a rare variant of chondrosarcomas characterized by
      a bimorphic pattern with areas of the undifferentiated malignant small cells and
      well differentiated cartilaginous islands.(1) It occurs most commonly in the bone
      but can also occur in the extraskeletal soft tissues, the brain, and the
      meninges. This type of tumor has also been described in the eyelids,
      parapharyngeal space, mediastinum, and the kidney.(1-5) An origin from the large
      vessels has not been reported in the medical literature. The authors report a
      case of mesenchymal chondrosarcoma originating from the femoral vein in a 28-year
      old female patient, treated by the wide-margin resection.

PMID- 12514603
TI  - Leiomyosarcoma of the popliteal artery: case report and review of the literature.
AB  - Vascular leiomyosarcomas are rare tumors, and only 21 have been described as
      developing in the systemic arteries. We present a case, the sixth in the
      literature, of a leiomyosarcoma originating in the popliteal artery of a 67-year
      old woman treated with en bloc excision of the neoplasia and the artery followed
      by a popliteal tibioperoneal trunk bypass. The patient then was underwent
      adjuvant radiotherapy and chemotherapy. After 31 months of follow-up, the patient
      has mild claudication but does not have either recurrence or metastasis.

PMID- 12514604
TI  - Asymptomatic internal carotid artery aneurysm.

PMID- 12514605
TI  - Dialysis access-associated steal syndrome: the intraoperative use of duplex
      ultrasound scan.
AB  - Dialysis access-associated steal syndrome (DASS) is an uncommon but serious
      complication after the creation of an arteriovenous shunt for hemodialysis and is
      related to an excess perfusion of the fistula. Several surgical options have been
      described for DASS correction. To achieve an adequate distribution of the blood
      flow towards the fistula and the hand, intraoperative duplex ultrasound scan
      monitoring was used in this preliminary communication to control the surgical
      reduction of volume flow through the fistula. The shunt flow was not estimated
      with direct insonation of the shunt but calculated from the difference of the
      bilateral subclavian artery volume flow rates. This new technique has several
      advantages over a direct shunt evaluation that are discussed in this report.
      Three patients with DASS are described in whom the technique was successfully
      applied and led to a normalization of the hand perfusion and to the maintenance
      of a long-term patency of the fistula.

PMID- 12514606
TI  - The use of an aortoiliac side-arm conduit to maintain distal perfusion during
      thoracoabdominal aortic aneurysm repair.
AB  - Thoracoabdominal aneurysm repair continues to be associated with a significant
      risk of operative complications, many of which are related to the prolonged
      period of aortic cross clamping inherent in the procedure. A variety of adjuvant
      techniques have been used in attempts to decrease morbidity, including
      atriofemoral extracorporal bypass, subarachnoid drainage, epidural cooling, and
      preliminary axillofemoral bypass. Herein is described a method to maintain distal
      perfusion with a side-arm conduit, originating from the most proximal aspect of
      the aortic graft and terminating on the left iliac artery. The technique has the
      potential to minimize hemodynamic instability while decreasing the period of
      pelvic and lower extremity ischemia and simplifying reattachment of aortic branch
      vessels. This method provides another option that can be considered in these
      technically demanding operative procedures.

PMID- 12514607
TI  - Rib-cross thoracotomy for replacement of the thoracoabdominal or total descending
      aorta.
AB  - We describe the use of rib-cross thoracotomy and costal coaptation pins made with
      bioabsorbable poly-L-lactide for rib approximation. This thoracotomy provided an
      excellent intraoperative exposure of the entire descending aorta and
      thoracoabdominal aorta in patients with extended thoracoabdominal aortic aneurysm
      without increase in postoperative morbidity.

PMID- 12514608
TI  - Regarding "thrombin injection for failed stent graft repair of perforated
      atherosclerotic aortic ulcer".

PMID- 12514609
TI  - Regarding "The 'C' of CEAP: suggested definitions and refinements: an
      International Union of Phlebology conference of experts".

PMID- 12514610
TI  - The principles of cost-effectiveness analysis and their application.
AB  - The current healthcare environment requires the evaluation of both the costs and
      benefits of alternative interventions for a given clinical problem. Given the
      increased interest in the economic evaluation of healthcare interventions, this
      article briefly defines various forms of economic evaluations and describes some
      useful steps for conducting appraisals of cost-effectiveness analyses. Studies of
      competing methods of treatment of abdominal aortic aneurysms greater than 5 cm
      are used as a clinical example of interest to the readers of this Journal. Rather
      than actually conducting such an analysis with existing data, we describe the
      principles for conducting or reviewing an economic analysis with factitious data.

PMID- 12514611
TI  - Ethics of patenting surgical procedures.

PMID- 12514612
TI  - Regarding "The mechanism of venous valve closure in normal physiological
      conditions".

PMID- 12514614
TI  - Regarding "Vascular access survival and incidence of revisions: a comparison of
      prosthetic grafts, simple autogenous fistulas, and venous transposition fistulas
      from the United States Renal Data System Dialysis Morbidity and Mortality Study".

PMID- 12514615
TI  - Regarding "Carotid artery closure for endarterectomy does not influence results
      of angioplasty-stenting for restenosis".

PMID- 12514617
TI  - Regarding "Carotid endarterectomy with routine electroencephalography and
      selective shunting: influence of contralateral internal carotid artery occlusion
      and utility in prevention of perioperative strokes".

PMID- 12514618
TI  - Regarding "Carotid endarterectomy with routine electroencephalography and
      selective shunting: influence of contralateral internal carotid artery occlusion
      and utility in prevention of perioperative strokes".

PMID- 12514620
TI  - Regarding "Endovenous treatment of the greater saphenous vein with a 940-nm diode
      laser: thrombolytic occlusion after endoluminal thermal damage by laser-generated
      steam bubbles".

PMID- 12514622
TI  - The question of evolution of an innovation over time.

PMID- 12514624
TI  - Regarding "Differential gene expression in human abdominal aorta: aneurysmal
      versus occlusive disease".

PMID- 12514626
TI  - Regarding "A spontaneous rupture of the external iliac vein revealed as a
      phlegmasia cerulea dolens with acute lower limb ischemia: case report and review
      of the literature".

PMID- 12514628
TI  - Usefulness of combined quantitative assessment of myocardial perfusion and
      velocities by myocardial contrast and doppler tissue echocardiography during
      coronary blood flow reduction.
AB  - OBJECTIVES: We sought to characterize regional myocardial perfusion and
      contraction in a closed-chest swine model during and after coronary blood flow
      reduction using myocardial contrast and Doppler tissue echocardiography. METHODS
      AND RESULTS: Regional myocardial perfusion was assessed by myocardial contrast
      echocardiography using the corrected contrast peak intensity (baseline-subtracted
      contrast peak intensity), the peak intensity ratio (contrast peak intensity in
      ischemic/control wall), and a transmural video-intensity gradient. Regional peak
      systolic velocities and strain rate were measured using M-mode color Doppler
      tissue echocardiography. In 12 pigs, coronary blood flow reduction resulted in a
      significant decrease in peak intensity ratio and in peak systolic velocities in
      the subendocardium. At baseline and during ischemia, corrected contrast peak
      intensity and peak systolic velocities in the subendocardium, video-intensity
      gradient, and strain rate were closely related (r = 0.88 and 0.93, respectively).
      After reperfusion, in contrast to peak systolic strain rate that remained
      altered, the peak intensity ratio and video-intensity gradient recovered nearly
      baseline values. CONCLUSION: The combination of myocardial contrast and Doppler
      tissue echocardiography may distinguish between ischemic and postischemic
      myocardial wall dysfunction during severe coronary blood flow reduction.

PMID- 12514629
TI  - Is there a role for intravenous transpulmonary contrast imaging in pediatric
      stress echocardiography?
AB  - OBJECTIVE: Intravenous transpulmonary contrast echocardiography plays a
      significant role in the enhancement of endocardial border delineation during
      stress echocardiography in the adult population. The current study was conducted
      to evaluate the feasibility of intravenous transpulmonary contrast in pediatric
      patients and to compare the quality of endocardial visualization by harmonic 2
      dimensional (2D) imaging alone with harmonic 2D echocardiography with contrast
      imaging. METHODS: Twenty-two children, age 9.3 +/- 3.9 underwent dobutamine (19
      patients) or exercise (3 patients) stress echocardiography. None had intracardiac
      shunting. Each patient underwent both harmonic 2D imaging alone and harmonic 2D
      imaging with contrast administration at peak stress. Oxygen saturation, heart
      rate, and blood pressure were monitored. Endocardial delineation was evaluated by
      qualitative grading of 22 endomyocardial regional segments in each patient.
      Contrast images were graded by an echocardiographer who was blinded to the scores
      previously assigned to harmonic 2D echocardiography images. RESULTS: There were
      no changes in saturation, heart rate, or blood pressure during or after contrast
      administration. Use of contrast significantly improved endocardial visualization
      in 11 of 22 segments (P <.05), particularly lateral, apical, and anterior left
      ventricular wall segments. CONCLUSION: Intravenous intrapulmonary administration
      is feasible and has no obvious adverse effects in a small pediatric patient
      group. Contrast echocardiography improves endocardial border delineation over
      harmonic imaging in pediatric stress echocardiography.

PMID- 12514630
TI  - Further insights into the no-reflow phenomenon after primary angioplasty in acute
      myocardial infarction: the role of microthromboemboli.
AB  - We tested the hypothesis that when acute coronary occlusion is caused by
      thrombus, part of the no-reflow phenomenon may result from spontaneous or
      coronary angioplasty-induced microthromboemboli, and that this phenomenon may be
      partly or wholly reversible. Accordingly, a thrombus was created in the left
      anterior descending coronary artery of 6 dogs and was labeled in vivo with
      (99m)Tc-DMP-444 that binds to the IIb/IIIa platelet receptor. Angioplasty was
      then performed to obtain thrombolysis in myocardial infarction grade-3 flow.
      Myocardial contrast echocardiography was performed 15 and 60 minutes after
      recanalization to define perfusion defect size. (99m)Tc-autoradiography and
      infarct size (IS) measurement were performed postmortem. An additional 5 dogs
      with coronary artery ligation followed by reperfusion served as control animals.
      These dogs also underwent myocardial contrast echocardiography and in vivo
      labeling with (99m)Tc-DMP-44. (99m)Tc uptake was significantly higher in the
      reperfused bed in dogs with thrombus compared with control dogs (2.7 +/- 0.9 vs
      1.4 +/- 0.3 counts/pixel(-1)/min(-1), P =.01) indicating the presence of
      microthromboemboli. Perfusion defect size early (15 minutes) after recanalization
      was smaller than the hot spot on autoradiography and overestimated IS in dogs
      with thrombus. Perfusion defect size decreased with time and was closer to IS 60
      minutes after recanalization. The dogs with thrombi demonstrated larger IS/risk
      area ratios compared with the 5 control dogs (46 +/- 6% vs 27 +/- 12%, P =.04).
      We conclude that part of the no-reflow phenomenon seen after angioplasty in acute
      coronary thrombosis is a result of microthromboemboli and is mostly reversible.
      No reflow late after reperfusion is a result of tissue necrosis. The thrombus
      burden also affects ultimate IS.

PMID- 12514631
TI  - Determination of left ventricular ejection fraction using intravenous contrast
      and a semiautomated border detection algorithm.
AB  - Manual endocardial tracing using Simpson's method (MANUAL SIMP) provides an
      accurate assessment of left-ventricular ejection fraction (LVEF). We have
      previously demonstrated in patients who are difficult to image: (1) the
      incremental accuracy of contrast-enhanced power harmonic imaging and MANUAL SIMP
      in the calculation of LVEF; and (2) the use of intravenous contrast-combined
      MANUAL SIMP was the most accurate method of LVEF determination. However, MANUAL
      SIMP is time-consuming, requires accurate planimetry of the endocardial borders,
      and is difficult to apply routinely in the clinical situation. The current study
      prospectively studied the accuracy of intravenous contrast and a semiautomated
      endocardial border detection algorithm in the determination of LVEF in 51
      patients with suboptimal images. LVEF was also calculated using contrast-enhanced
      power harmonic imaging and MANUAL SIMP. We demonstrated that there was good
      agreement between LVEF determined using both MANUAL SIMP and semiautomated
      endocardial border detection, and radionuclide angiography (standard of
      comparison).

PMID- 12514632
TI  - Analysis of global systolic and diastolic left ventricular performance using
      volume-time curves by real-time three-dimensional echocardiography.
AB  - BACKGROUND: Left ventricular (LV) volume-time curves (VTC) have been described to
      provide quantitative data on the dynamics of global LV performance beyond
      ejection fraction. However, generation of VTCs by conventional 2-dimensional
      imaging techniques is inherently limited because of inaccurate geometric volume
      assumptions. We, therefore, studied whether the new concept of volumetric
      scanning as realized by real-time 3-dimensional echocardiography (RT-3DE) can be
      used to provide accurate VTCs. METHODS: In 30 healthy participants, VTCs were
      generated from 18 to 24 absolute LV volumes per second by transthoracic RT-3DE
      and compared with magnetic resonance imaging (MRI) used for reference. LVs were
      traced manually in 9 to 11 parallel, short-axis planes and volumes calculated by
      disk method. From VTCs, we determined peak ejection rate (PER), peak early
      filling rate (PFR), time to PER and PFR, and end-diastolic and end-systolic
      volumes. For initial clinical application, 2 patient groups of coronary (n = 15)
      and hypertensive heart disease (n = 16) were studied. RESULTS: In healthy
      participants, VTCs agreed with MRI (mean errors: PER, -39 +/- 67 mL/s; PFR, -18
      +/- 84 mL/s; time to PER, 8 +/- 21 milliseconds; time to PFR 4 +/- 18
      milliseconds [not significant vs 0]) whereas VTCs in coronary and hypertensive
      groups revealed significantly impaired diastolic function. Scanning time for VTCs
      was only 1 to 2 minutes by RT-3DE and 8 +/- 2 minutes by MRI (P <.001) and time
      for offline analysis was 22 +/- 5 minutes versus 24 +/- 4 minutes by MRI (not
      significant). CONCLUSIONS: Generation of VTCs by RT-3DE is feasible and shows
      excellent agreement with MRI used for reference. Thus, VTCs by RT-3DE is a
      promising new approach providing access to quantitative information on global LV
      performance such as LV filling rates that is currently unavailable for the
      cardiologist.

PMID- 12514633
TI  - Real-time three-dimensional color doppler evaluation of the flow convergence zone
      for quantification of mitral regurgitation: Validation experimental animal study
      and initial clinical experience.
AB  - BACKGROUND: Pitfalls of the flow convergence (FC) method, including 2-dimensional
      imaging of the 3-dimensional (3D) geometry of the FC surface, can lead to
      erroneous quantification of mitral regurgitation (MR). This limitation may be
      mitigated by the use of real-time 3D color Doppler echocardiography (CE). Our
      objective was to validate a real-time 3D navigation method for MR quantification.
      METHODS: In 12 sheep with surgically induced chronic MR, 37 different hemodynamic
      conditions were studied with real-time 3DCE. Using real-time 3D navigation, the
      radius of the largest hemispherical FC zone was located and measured. MR volume
      was quantified according to the FC method after observing the shape of FC in 3D
      space. Aortic and mitral electromagnetic flow probes and meters were balanced
      against each other to determine reference MR volume. As an initial clinical
      application study, 22 patients with chronic MR were also studied with this real
      time 3DCE-FC method. Left ventricular (LV) outflow tract automated cardiac flow
      measurement (Toshiba Corp, Tokyo, Japan) and real-time 3D LV stroke volume were
      used to quantify the reference MR volume (MR volume = 3DLV stroke volume -
      automated cardiac flow measurement). RESULTS: In the sheep model, a good
      correlation and agreement was seen between MR volume by real-time 3DCE and
      electromagnetic (y = 0.77x + 1.48, r = 0.87, P <.001, delta = -0.91 +/- 2.65 mL).
      In patients, real-time 3DCE-derived MR volume also showed a good correlation and
      agreement with the reference method (y = 0.89x - 0.38, r = 0.93, P <.001, delta =
      -4.8 +/- 7.6 mL). CONCLUSIONS: real-time 3DCE can capture the entire FC image,
      permitting geometrical recognition of the FC zone geometry and reliable MR
      quantification.

PMID- 12514634
TI  - Anatomic three-dimensional echocardiographic correlation of bicuspid aortic
      valve.
AB  - This study was undertaken to verify the echocardiographic characteristics of
      bicuspid aortic valve (AV) using 3-dimensional transesophageal echocardiography
      by comparing the findings with anatomic examination of autopsy specimens from
      carriers of this condition. Three-dimensional reconstructions of transesophageal
      echocardiograms were performed on 14 patients with bicuspid AV, and 20 autopsy
      specimens of bicuspid AVs were analyzed. Echocardiographic images and autopsy
      material were correlated. Two variants of bicuspid aorta were identified. In
      group I the AV had 2 leaflets. This group included 9 (9/14) 3-dimensional
      echocardiographic studies and 13 (13/20) necropsies. In group II 3 sigmoid
      leaflets had originally developed and 2 underwent dysplastic fusion, resulting in
      functionally bicuspid valves. Five (5/14) echocardiographic studies and 7 (7/20)
      anatomic specimens fell into this category. There was a clear correspondence
      between anatomic and echocardiographic findings, which leads to the conclusion
      that 3-dimensional echocardiography is a technique that reliably defines the
      morphological details of bicuspid AV with the precision of anatomopathologic
      examination.

PMID- 12514635
TI  - Depth variation bias and interaction with gain setting in ultrasonic tissue
      characterization by integrated backscatter analysis.
AB  - Integrated backscatter signal (IBS) has been proposed as a tool to measure
      cardiac fibrosis. To overcome problems associated with machine settings and
      attenuation of the chest wall, IBS has been expressed in relation to posterior
      pericardium, as a variation across cardiac cycle, or both. Depth of the
      reflecting structure has never been considered as a source of variability.
      Accordingly, we studied the effect of structure depth on IBS and examined its
      interaction with gain setting. Backscatter signals were recorded from plastic
      phantoms containing identical structures set at increasing depth and in 1 healthy
      volunteer using silicone spacers to modify depth, on a wide range of gain
      settings. In the phantom, IBS signal linearly decreased with increasing depth and
      nonlinearly increased with increasing gain (all r(2) > 0.97). In the healthy
      volunteer, results from septum were very similar to the phantom experiment.
      Values of septal IBS were adjusted using multiple regression coefficients for
      gain and depth from the phantom experiment and resulted in a near-complete offset
      of effect of depth and gain on septal IBS (P = not significant for both gain and
      depth). These assumptions were also used to compare IBS analysis between
      hypertensive patients and patients with hypertrophic cardiomyopathy. Thus, depth
      and its relation with gain should be taken into account and might be almost fully
      predicted. Using appropriate regression modeling may allow analysis in optimal
      imaging conditions, tolerating between-patient comparisons even in limited
      diastolic frames.

PMID- 12514636
TI  - Multiplane transesophageal echocardiography performed according to the guidelines
      of the American Society of Echocardiography in patients with mitral valve
      prolapse, flail, and endocarditis: diagnostic accuracy in the identification of
      mitral regurgitant defects by correlation with surgical findings.
AB  - Multiplane transesophageal echocardiography is a useful tool to study mitral
      regurgitation. We evaluated the diagnostic accuracy of multiplane transesophageal
      echocardiography performed according to the guidelines of the American Society of
      Echocardiography. We used 4 midesophageal and 2 transgastric views in 313
      patients with degenerative lesions, endocarditic lesions, or both to identify
      regurgitant defects, comparing transesophageal echocardiography results with
      surgical findings. The overall diagnostic accuracy using individual scallops was
      97.2% (P <.00001) with a sensitivity of 96.6% and a specificity of 97.6%.
      Considering the single sections of the mitral valve, an accuracy of 98%, 97.1%,
      and 98%, was found, respectively, for the lateral, middle, and medial third of
      the anterior leaflet. For the posterior leaflet, the accuracy was 98% for the
      lateral scallop, 98.4% for the middle, and 96.1% for the medial. This strategy
      provides good accuracy in diagnosing both simple and challenging mitral-valve
      lesions and its widespread use should be recommended.

PMID- 12514637
TI  - Sensitivity of transthoracic versus transesophageal echocardiography for the
      detection of native valve vegetations in the modern era.
AB  - BACKGROUND: Thirteen years ago, transthoracic echocardiography (TTE) was found to
      be less sensitive than transesophageal echocardiography (TEE) for native valve
      vegetations. Since then, harmonic imaging and other advances have improved TTE.
      How this affects the sensitivity of TTE is unknown. METHODS: Fifty patients with
      echocardiography-diagnosed endocarditis had TTE and TEE examinations on high-end
      machines. These were matched for date of study with 50 patients who had TTE and
      TEE examinations that were negative for vegetations. RESULTS: A total of 51
      vegetations were seen on TEE. The sensitivity of TTE for vegetations was only 55%
      (aortic 50% [12/24]; mitral 62% [16/26]; tricuspid 0% [0/1]). Anatomic valvular
      abnormalities did not alter the sensitivity of TTE (P =.42 for mitral; P =.97 for
      aortic valves). However, larger vegetations were more likely to be found by TTE.
      CONCLUSION: Despite advances in imaging during 12 years, TTE is still insensitive
      compared with TEE for the detection of native valve vegetations, and fails to
      demonstrate nearly half of them.

PMID- 12514638
TI  - Patent foramen ovale: anatomy versus pathophysiology--which determines stroke
      risk?
AB  - This study investigated anatomic and pathophysiologic variables that may
      determine which patent foramen ovale (PFO) are associated with cerebrovascular
      accidents (CVAs). Anatomic features of a PFO have been identified as risk factors
      that predispose certain people to cryptogenic strokes (strokes of unknown cause).
      However, potential pathophysiologic variables that can determine the pressure
      gradient between left and right atria, which could influence the right-to-left
      shunt through a PFO, have not been examined. A retrospective study included 78
      consecutive patients in whom PFOs were detected during routine transesophageal
      echocardiography examination. Group I included 36 patients with CVAs of unknown
      cause (cryptogenic stroke). Group II included 42 patients without CVAs whose PFOs
      were incidental findings. Anatomic features measured included separation and
      overlap between septum primum and septum secundum, interatrial septal motion, and
      the relative size of the right-to-left shunt with peripheral saline solution
      contrast injections. Pathophysiologic variables considered were those that could
      cause elevated left atrial pressure, thereby minimizing the right-to-left
      shunt.Patients with a clinical neurologic event (group I) had a larger right-to
      left shunt volume of contrast bubbles than did patients with asymptomatic PFO
      (group II; P =.004). The size of the overlap between septum primum and septum
      secundum was less in patients from group I as compared with patients from group
      II (7.5 +/- 3.4 mm versus 9.9 +/- 6.0 mm; P =.026). However, other anatomic
      features of PFO that are determinants of the "opening" were not significantly
      different between the 2 groups. No statistically significant difference was found
      in the distance of the separation between septum primum and septum secundum (2.5
      +/- 2.0 mm versus 1.9 +/- 1.6 mm; P = not significant). The prevalence of
      interatrial septal aneurysm was also similar between the 2 groups (28% versus
      21%; P = not significant). However, the prevalence of variables that could
      potentially raise left atrial pressure was greater in patients without CVA as
      compared with those with a CVA (48% versus 14%; P =.01). In our study, anatomic
      features alone did not determine interatrial shunt size and pathophysiologic
      variables that could raise left atrial pressures did differentiate between
      patients with a PFO with a CVA/transient ischemic attack and those without it.
      Thus, both anatomic and pathophysiologic mechanisms should be considered in
      determination of the potential clinical significance of a PFO.

PMID- 12514639
TI  - Mechanism and incidence of notched pulmonary venous atrial reversal wave.
AB  - In certain patients, pulmonary venous flow pattern obtained by the pulsed wave
      Doppler during transesophageal echocardiography shows a notching on the atrial
      reversal (A) wave. However, the incidence or the mechanism of this notched A wave
      has not been described. After transthoracic echocardiographic evaluation for the
      chamber sizes, wall thickness, and left-ventricular function, transesophageal
      echocardiography was performed in 100 patients with in sinus rhythm. Discernible
      pulmonary venous A wave was observed in 46 patients. Among these 46 patients,
      notched A wave was observed in 11 (31%). In 4 patients with notched A wave, left
      atrial pressure waveforms could be obtained during mitral balloon valvuloplasty.
      In all these patients, left-atrial pressure waveforms showed prominent c waves.
      In 2 patients, transesophageal echocardiography was repeated after mitral balloon
      valvuloplasty. Late peak of the notched A wave decreased with the decrease in the
      magnitude of rise in left-atrial c wave. Among the transthoracic
      echocardiographic parameters, patients with notching (n = 11) had significantly
      larger left atriums than patients without notching (n = 35)(49.3 +/- 6.2 vs 37.3
      +/- 4.4 mm, P <.0001). There were no significant differences in left-ventricular
      dimensions, wall thickness, and ejection fraction. In conclusion, notched
      pulmonary venous A wave indicates the presence of left-atrial c wave; and
      presence of left-atrial c wave may represent decreased left-atrial compliance.

PMID- 12514640
TI  - An unusual cause of diastolic mitral regurgitation as a result of sterile
      perforation of the mitral valve.
AB  - We report the case of a 50-year-old man in whom a supracristal ventricular septal
      defect led to aortic regurgitation and, thus, to consecutive sterile perforation
      of the anterior mitral leaflet, culminating in the development of severe systolic
      and diastolic mitral regurgitation. Aortic regurgitation as a result of valve
      prolapse caused by a supracristal (conal) ventricular septal defect is a well
      known phenomenon. The same is true for the origin of mitral jet lesions in
      patients with infective endocarditis of the aortic valve. As of yet, there have
      been no reports about the acquisition of mitral valve perforations in patients
      without the history of vegetations. Moreover, the occurrence of diastolic mitral
      regurgitation is usually associated with atrioventricular pressure reversal, a
      phenomenon that was not present in our patient. The unique comorbidity was easy
      to detect with Doppler echocardiography, supported by transesophageal 2
      dimensional and dynamic 3-dimensional echocardiography for preoperative surgical
      treatment.

PMID- 12514641
TI  - Mixed total anomalous pulmonary venous connection: Case report with bilateral
      venous collectors.
AB  - We present a case report of a 3-month-old boy with a mixed total anomalous
      pulmonary venous connection. The patient had situs solitus, small atrial septal
      defect, and 2 separate venous collectors. The right pulmonary veins drained
      through a right-sided venous collector into the coronary sinus. The left-sided
      pulmonary veins drained through the left-sided venous collector directly into the
      right superior vena cava. The use of the echocardiogram and Doppler color flow
      mapping to establish a detailed morphologic analysis, the sites of connection,
      and the presence of pulmonary venous obstructions as well as the value of this
      information to facilitate a successful surgical repair are discussed.

PMID- 12514642
TI  - Effects of balloon valvuloplasty on left anterior descending coronary artery
      blood flow in a neonate with critical aortic stenosis with transthoracic doppler
      echocardiography.
AB  - Doppler echocardiography has recently been used in the assessment of coronary
      flow dynamics. We described the application of transthoracic Doppler
      echocardiography for the measurement of the coronary flow before and after
      balloon valvuloplasty in a neonate with critical aortic stenosis. In this case,
      coronary flow volume/left ventricular mass ratio increased after the procedure,
      suggesting the improvement of myocardial blood perfusion. Thus, this technique
      may provide additional information about coronary flow dynamics in patients with
      critical aortic stenosis.

PMID- 12514643
TI  - Two-dimensional echocardiographic diagnosis of double outlet left ventricle with
      subaortic ventricular septal defect, pulmonary stenosis, and a hypoplastic left
      ventricle.
AB  - Double outlet left ventricle (DOLV) is a rare congenital cardiac malformation in
      which both the pulmonary artery and the aorta arise exclusively or predominantly
      from the morphologic left ventricle. We describe a case of DOLV with situs
      solitus, d-loop ventricles, d-malposition of the great arteries (S, D, D), severe
      pulmonary stenosis, and a subaortic ventricular septal defect in which the left
      ventricle was also severely hypoplastic. The anatomic features were shown with 2
      dimensional echocardiography, and the diagnosis was later confirmed at cardiac
      catheterization. Many morphologic variations of this malformation have been
      described but to the our knowledge DOLV with a hypoplastic left ventricle has not
      been reported before.

PMID- 12514644
TI  - Noncompaction of the ventricular myocardium: the use of contrast-enhanced
      echocardiography in diagnosis.
AB  - We describe a case of noncompaction of the ventricular myocardium diagnosed in
      the preoperative evaluation of a patient undergoing renal transplantation.
      Ventricular noncompaction is characterized by numerous prominent trabecular
      recesses with intratrabecular blood from the ventricular cavity. Color Doppler
      was suggestive of intramyocardial flow. With contrast-enhanced echocardiography
      the endocardial borders were clearly demarcated, allowing for visualization of
      trabecular recesses and intratrabecular flow. Contrast-enhanced echocardiography
      facilitates the diagnosis of noncompaction of the ventricular myocardium,
      circumventing the need for invasive diagnostic testing.

PMID- 12514645
TI  - Mechanical prosthetic valve-associated strands: Pathologic correlates to
      transesophageal echocardiography.
AB  - Echocardiographic detection of prosthetic valve-associated strands has previously
      been reported, but their clinical relevance is unclear. Limited data are
      available regarding the cause, composition, and natural history of these strands.
      This report presents the gross and histopathologic findings of an explanted
      mechanical prosthetic valve shown by transesophageal echocardiography to have
      several strands. The patient had not experienced prior neurologic symptoms.
      Potential causes of strand formation in various clinical settings are also
      discussed.

PMID- 12514646
TI  - Prehospital management of acute ST-elevation myocardial infarction: a time for
      reappraisal in North America.
AB  - Although the medical and technologic revolution in the last 3 decades has
      improved clinical outcome in patients sustaining acute ST-elevation myocardial
      infarction (STEMI), residual morbidity and mortality remain major health
      concerns. The critical roles of temporal delay and optimal sustained patency as
      modulators of successful reperfusion have been repeatedly demonstrated, and
      investigation into the ideal interface between pharmacologic and mechanical
      reperfusion continues. Despite physician awareness and patient education
      programs, time from symptom onset to treatment in STEMI remains stalled at
      approximately 3 hours for pharmacologic reperfusion, as documented in major
      clinical trials. Multifaceted improvements with advanced paramedic training,
      transmittable 12-lead electrocardiograms, and bolus fibrinolytics facilitate
      potential prehospital diagnosis and treatment. Thus, as we proceed into the 21st
      century, it is essential to reexamine strategies for addressing these and other
      issues relating to the process of delivering optimal care to most patients with
      STEMI. Especially notable are the opportunities provided through prehospital
      management with initiation of therapy, triage to appropriate hospitals, or both
      as major potential avenues to further enhance patient outcomes. We review past
      research in prehospital therapy for STEMI and practical impediments to
      implementation to establish a framework for interpretation of future
      developments.

PMID- 12514647
TI  - Double negatives.

PMID- 12514648
TI  - Physician adherence to clinical practice guidelines: does it really matter?

PMID- 12514649
TI  - Hierarchical modeling: its time has come.

PMID- 12514650
TI  - Adherence to practice guidelines: the role of specialty society guidelines.
AB  - BACKGROUND: Physician adherence to guidelines is often poor, but the reasons have
      not been completely studied. We investigated whether physician adherence to
      guidelines for percutaneous transluminal coronary angioplasty (PTCA) and coronary
      artery bypass grafting (CABG) varied by source, development methods, or the
      extent of their evidence-base. METHODS AND RESULTS: We assessed adherence to
      guidelines developed by the American College of Cardiology/American Heart
      Association (ACC/AHA) for PTCA (1988 and 1993) and for CABG (1990) and guidelines
      developed by RAND for PTCA and CABG in 1990. We randomly sampled patients on
      Medicare who were undergoing coronary angiography in 5 states in 1991 and 1992,
      extracting clinical and laboratory data from medical records and using computer
      programs to classify the appropriateness of each procedure. A total of 543 PTCA
      and 676 CABG procedures were studied. By use of the 1988 ACC/AHA guidelines, 30%
      of PTCAs were rated class III (inappropriate), whereas 24% were class III by use
      of the 1993 guidelines. Only 1.5% of CABG procedures were class III with ACC/AHA
      guidelines. By use of RAND guidelines, 12% of PTCA and 9% of CABG procedures were
      classified as inappropriate. CONCLUSIONS: Adherence to guidelines is higher when
      the recommendations are supported by evidence from randomized clinical trials
      (CABG). The credibility of the source and familiarity with the guidelines do not
      ensure compliance. When evidence is lacking, as with PTCA at the time of this
      study, guideline recommendations may lag behind appropriate changes in clinical
      practice. More frequent revisions coupled with on-line access have the potential
      to make guidelines more useful.

PMID- 12514651
TI  - Comparing hierarchical modeling with traditional logistic regression analysis
      among patients hospitalized with acute myocardial infarction: should we be
      analyzing cardiovascular outcomes data differently?
AB  - BACKGROUND: Data in health research are frequently structured hierarchically. For
      example, data may consist of patients treated by physicians who in turn practice
      in hospitals. Traditional statistical techniques ignore the possible correlation
      of outcomes within a given practice or hospital. Furthermore, imputing
      characteristics measured at higher levels of the hierarchy to the patient-level
      artificially inflates the amount of available information on the effect of higher
      level characteristics on outcomes. METHODS: Conventional logistic regression
      models and multilevel logistic regression models were fit to a cross-sectional
      cohort of patients hospitalized with a diagnosis of acute myocardial infarction.
      The statistical significance of the effect of patient, physician, and hospital
      characteristics on patient outcomes was compared between the 2 modeling
      strategies. RESULTS: The 2 analytic strategies agreed well on the effect of
      patient characteristics on outcomes. According to the traditional analysis,
      teaching status was statistically significantly associated with 5 of the 9
      outcomes, whereas the multilevel models did not find a statistically significant
      association between teaching status and any patient outcomes. Similarly, the
      traditional and multilevel models disagreed on the statistical significance of
      the effect of being treated at a revascularization hospital and 3 patient
      outcomes. CONCLUSIONS: In comparing the resultant models, we see that false
      inferences can be drawn by ignoring the structure of the data. Conventional
      logistic regression tended to increase the statistical significance for the
      effects of variables measured at the hospital-level compared to the level of
      significance indicated by the multilevel model.

PMID- 12514652
TI  - Quality of life and time trade-off utility measures in patients with coronary
      artery disease.
AB  - BACKGROUND: Contemporary clinical trials commonly measure quality of life and
      medical costs to establish whether therapies are both effective and cost
      effective. Cost-effectiveness analysis, however, requires a measure of patient
      utility or preferences for various health states. Because utilities are not often
      measured directly, we sought to develop a method of translating standard quality
      of-life scales into a patient utility measure. METHODS: Five hundred fifty-three
      patients enrolled in the Bypass Angioplasty Revascularization Investigation Study
      of Economics and Quality of Life completed a battery of quality-of-life measures
      and a time trade-off utility assessment an average of 7.3 years after random
      assignment. RESULTS: The mean time trade-off score was 8.54 (SD = 2.53) out of a
      maximum of 10; median score was 9.95. The distribution of scores was skewed, with
      12% of patients at the highest possible score of 10. Patients with recurrent
      angina had significantly lower time trade-off scores than patients without angina
      (mean 7.03 vs 8.70, P <.05). Time trade-off scores were moderately correlated
      with each quality-of-life measure (Spearman coefficients 0.38-0.52). Time trade
      off scores could be predicted by combinations of 4 (r2 = 0.29), 5 (r2 = 0.31), or
      6 (r2 = 0.32) variables. CONCLUSIONS: Time trade-off utility scores can be
      inferred from commonly used quality-of-life measures. Angina significantly
      reduces patient utility scores.

PMID- 12514653
TI  - No-reflow is an independent predictor of death and myocardial infarction after
      percutaneous coronary intervention.
AB  - BACKGROUND: No-reflow occurring during percutaneous coronary intervention (PCI)
      has been associated with poor inhospital outcomes. The objectives of this
      analysis were to evaluate the occurrence of no-reflow as an independent predictor
      of adverse events and to determine whether treatment with intracoronary
      vasodilator therapy affected clinical outcomes. METHODS: We prospectively
      collected data from 4264 consecutive patients undergoing PCI, identifying those
      with no-reflow, and analyzed their treatments and clinical outcomes. RESULTS: No
      reflow was identified in 135 of 4264 patients (3.2%). Baseline demographics were
      comparable, but patients with no-reflow were more likely to have acute myocardial
      infarction, unstable angina, and cardiogenic shock and to have undergone
      saphenous vein graft interventions. No-reflow was highly predictive of
      postprocedural myocardial infarction (17.7% vs 3.5% in patients without no
      reflow, P <.001) and death (7.4% vs 2.0%, P <.001) and remained a strong
      independent predictor of death or myocardial infarction after multivariate
      analysis (odds ratio 3.6, P <.001). The administration of intracoronary
      verapamil, sodium nitroprusside, or both was not associated with a reduction in
      the rate of death or myocardial infarction (adjusted odds ratio of death or
      myocardial infarction 1.04, P =.945 for nitroprusside; and adjusted odds ratio of
      death or myocardial infarction 0.94, P =.91 for verapamil), despite an
      improvement in angiographic flow rates for patients treated with sodium
      nitroprusside. CONCLUSIONS: No-reflow is a strong independent predictor of
      inhospital mortality and postprocedural myocardial infarction. Administration of
      verapamil or sodium nitroprusside was not associated with improved inhospital
      outcomes in patients with no-reflow, although anterograde flow rates were
      improved in patients treated with sodium nitroprusside.

PMID- 12514654
TI  - Primary coronary angioplasty compared with intravenous thrombolytic therapy for
      acute myocardial infarction: six-month follow up and analysis of individual
      patient data from randomized trials.
AB  - BACKGROUND: Overviews of trials suggest that percutaneous transluminal coronary
      angioplasty (PTCA) may be more effective than thrombolysis. However, whether
      these effects are sustained beyond hospital discharge, and the extent to which
      the results are applicable to a broad cross section of patients and the wider
      community are unknown. We compared the effectiveness of primary PTCA and
      thrombolysis in acute myocardial infarction during a 6-month follow-up period.
      METHODS: Detailed individual patient data were collected from randomized trials
      commenced from 1989 to 1996 that compared primary PTCA with thrombolysis. Data
      were combined to produce estimates of relative reduction in events at 30 days and
      6 months for the group and for predefined clinical subgroups. Treatment effects
      were also assessed in relation to several study-related factors. RESULTS: Eleven
      trials were identified. The mortality rate at 30 days was 4.3% for 1348 patients
      randomized to undergo PTCA, and 6.9% for 1377 patients assigned to thrombolytic
      therapy (relative risk [RR] 0.62, 95% CI 0.44-0.86, P =.004). At 6 months, the
      mortality rate was 6.2% for PTCA and 8.2% for thrombolysis (RR 0.73, 95% CI 0.55
      0.98, P =.04). Combined death and reinfarction rates at 30 days were 7.0% for
      PTCA and 12.9% for thrombolysis, with a sustained effect at 6 months (RR 0.60,
      95% CI 0.48-0.75, P <.0001). The risk of hemorrhagic stroke at 30 days was lower
      in the PTCA group (RR 0.06, 95% CI 0.0-0.50, P =.009). The relative treatment
      effect did not vary across clinically important subgroups, but the absolute
      benefit varied according to baseline risk. The relative treatment effect varied
      across the trials and according to the thrombolytic comparator used, the delay in
      performing PTCA, and the recruitment rate. CONCLUSION: In the context of these
      trials, primary PTCA was more effective than thrombolytic therapy in reducing
      death, reinfarction, and stroke, with the greatest absolute benefit in patients
      who were at the highest risk. These benefits appear to be sustained for 6 months.
      The effect of treatment varied significantly across the trials, and this raises
      issues about how widely the results can be applied.

PMID- 12514655
TI  - A randomized trial assessing the effect of coumarins started before coronary
      angioplasty on restenosis: results of the 6-month angiographic substudy of the
      Balloon Angioplasty and Anticoagulation Study (BAAS).
AB  - BACKGROUND: Thrombus formation during coronary angioplasty may play a role in the
      restenosis process. METHODS: The effect of pretreatment with coumarins on 6-month
      angiographic outcome was studied. In addition, the effect of "optimal"
      anticoagulation, defined as an international normalized ratio >70% of the follow
      up time in the target range, was studied. A total of 261 patients were assigned
      to aspirin alone (ASA group) and 270 patients to aspirin plus coumarins started 1
      week before the procedure (coumarin group). RESULTS: The mean international
      normalized ratio was 2.7 +/- 1.2 at the start of the procedure and 3.1 +/- 0.5
      during follow up. Quantitative coronary analysis was performed on 301 lesions in
      the ASA group and of 297 lesions in the coumarin group. At 6 months, the minimal
      luminal diameter was similar in the ASA and coumarin groups. Optimal
      anticoagulation, however, was an independent predictor of a larger minimal
      luminal diameter at follow up (P =.01). CONCLUSION: Overall, coumarins do not
      improve angiographic outcome 6 months after coronary angioplasty.

PMID- 12514656
TI  - Altered coronary flow properties in diffuse coronary artery ectasia.
AB  - OBJECTIVES: The purpose of this study was to investigate coronary blood flow
      properties in patients with diffuse coronary artery ectasia (CAE) associated with
      exercise-induced myocardial ischemia. METHODS: Seventeen patients with diffuse
      CAE and without coexisting coronary artery stenosis were enrolled in the study
      (CAE group). CAE was defined as luminal dilatation 1.5 to 2 times that of the
      adjacent normal coronary artery segment or the diameter of the corresponding
      coronary artery of the control group when there was no normal segment. The age-
      and sex-matched control group (n = 20) comprised patients with normal epicardial
      coronary arteries. Coronary blood flow velocities were obtained invasively by use
      of Doppler scanning flow wire. Coronary flow reserve (CFR) was measured by
      administration of intracoronary papaverine as the hyperemic stimulus. Volumetric
      coronary blood flow was estimated by multiplying the velocity time integral of
      coronary blood flow with the cross-sectional area of the coronary artery and the
      heart rate. RESULTS: Fifteen patients with CAE, but none of the patients in the
      control group, had electrocardiographic signs of myocardial ischemia at peak
      exercise on ergometry. Baseline average peak velocities (APVs) of coronary blood
      flow were similar in the 2 groups. Peak hyperemic APVs of coronary blood flow
      were lower in the CAE group than in the control group (17.5 +/- 7.4 cm/s vs 41.5
      +/- 12.6 cm/s, respectively, P <.001). Volumetric coronary blood flow was
      significantly higher in the CAE group than in the control group, both at rest and
      at hyperemia (146.3 +/- 71.2 cm3/min vs 45.1 +/- 16.1 cm3/min, respectively, P
      <.001, and 202 +/- 87.3 cm3/min vs 104.1 +/- 37.6 cm3/min, respectively, P
      <.003). The mean CFR of the CAE group was significantly reduced compared with
      that of the control group (1.51 +/- 0.31 vs 2.67 +/- 0.52, respectively, P
      <.001). CONCLUSIONS: The CFR is significantly reduced in patients with diffuse
      CAE compared to a matched control group. Although volumetric coronary blood flow
      is significantly higher in CAE, microcirculatory dysfunction that is reflected as
      depressed CFR may be the underlying cause of exercise-induced myocardial
      ischemia.

PMID- 12514657
TI  - Frequency, patient characteristics, and outcomes of mild-to-moderate heart
      failure complicating ST-segment elevation acute myocardial infarction: lessons
      from 4 international fibrinolytic therapy trials.
AB  - BACKGROUND: There is a paucity of data on the incidence of mild-to-moderate heart
      failure (HF) complicating ST-segment elevation acute myocardial infarction (MI)
      and its impact on short-term outcomes. Our objective was to determine the
      incidence, timing, and consequences of mild-to-moderate HF complicating acute MI.
      METHODS: We examined the occurrence of death or death/recurrent MI (re-MI) in
      patients enrolled in the Global Utilization of Streptokinase and Tissue
      Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I), the Global Use of
      Strategies to Open Occluded Coronary Arteries (GUSTO IIb), the Global Use of
      Strategies to Open Occluded Coronary Arteries (GUSTO-III), and Assessment of the
      Safety and Efficacy of a New Thrombolytic (ASSENT-II) trials, which examined
      different fibrinolytic therapies for MI. We excluded patients who had cardiogenic
      shock (n = 2994) or unknown HF status at all time points (n = 13,716). Of the
      remaining 61,041 patients, 17,949 patients (29.4%) had HF, 1566 (8.7%) only at
      baseline, 10,339 (57.6%) only after admission, and 6044 (33.7%) at baseline and
      after. RESULTS: The incidence of HF was 32.5% in the United States and 26.9%
      elsewhere. At 30 days, death and death/re-MI occurred in 2% and 4% of patients
      without HF and 8% and 12% of patients with HF, respectively (2% and 4% of
      patients with HF only at baseline, 7% and 13% of patients with HF only after
      baseline, and 10% and 13% of patients with HF at baseline and later). By use of
      multivariable analyses, the presence of HF was associated with 1.55 times greater
      risk of dying at 30 days (95% CI 1.38-1.74) and 2.15 times greater risk of
      death/re-MI (95% CI 1.96-2.36). CONCLUSION: Mild-to-moderate HF is a frequent and
      ominous complication of MI, especially when it does not resolve or develops after
      admission.

PMID- 12514658
TI  - Double-blind comparison between zofenopril and lisinopril in patients with acute
      myocardial infarction: results of the Survival of Myocardial Infarction Long-term
      Evaluation-2 (SMILE-2) study.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been reported to
      be effective in placebo-controlled trials in various subsets of patients with
      acute myocardial infarction (MI). However, no direct comparisons have been
      performed between different ACE inhibitors in the same patient population.
      METHODS: This phase III, double-blind, parallel-group, multicenter study compared
      the safety and efficacy of zofenopril and lisinopril in 1024 thrombolyzed
      patients with acute MI. Patients, aged 18 to 75 years, were randomized to receive
      oral zofenopril (30-60 mg/day) or lisinopril (5-10 mg/day), starting within 12
      hours of completion of thrombolytic therapy and continuing for 42 days. The
      primary study end point was the incidence of severe hypotension (systolic blood
      pressure <90 mm Hg), either cumulative or drug-related. Secondary end points
      included additional safety and efficacy parameters. RESULTS: The overall
      incidence of severe hypotension was slightly 5 more reduced with zofenopril
      (10.9%) than with lisinopril (11.7%, P =.38). The incidence of drug-related
      severe hypotension was slightly but significantly lower with zofenopril than with
      lisinopril (6.7 vs 9.8%, 2-tailed P =.048). The 6-week mortality rate was 3.2% in
      the zofenopril group and 4.0% in the lisinopril group (P =.38), and no
      significant differences were observed in the incidence of major cardiovascular
      complications or any safety variables between the 2 ACE inhibitors. CONCLUSIONS:
      The SMILE-2 study demonstrates that both zofenopril and lisinopril are safe and
      associated with a rather low rate of severe hypotension when given in accordance
      with a dose-titrated scheme to thrombolyzed patients with acute MI. These
      findings could have a positive clinical impact and increase the proportion of
      patients with acute MI who can be safely treated with ACE inhibitors.

PMID- 12514659
TI  - Biochemical and clinical predictors of long-term outcome in patients with
      nonspecific chest pain and nondiagnostic electrocardiograms.
AB  - BACKGROUND: There are few data assessing the relative value of clinical factors
      and sensitive cardiac markers in determining the long-term prognosis of patients
      with chest pain. Likewise, little information exists about the long-term outcome
      of patients with chest pain who have negative markers of myocardial cell
      necrosis. This study addresses these issues in a cohort of patients with
      nonspecific chest pain and nondiagnostic electrocardiograms (ECGs). METHODS:
      Eligible subjects (n = 501) had experienced >15 minutes chest pain at rest during
      the previous 24 hours, but were found to be at low-risk for acute myocardial
      infarction (AMI) by means of a well-validated clinical algorithm. Cardiac
      troponin I, creatine kinase MB(mass), myoglobin, and myosin light chain-1 were
      collected at presentation and 3, 6, and 12 hours later. Patients were observed
      for a median of 31 months. The composite end point was death or AMI subsequent to
      the index admission. RESULTS: Cardiac troponin I was the best single biochemical
      predictor of outcome (risk ratio 2.34, 95% CI 1.31-4.17, P =.004), but was of
      less independent prognostic value than age and an abnormal presenting ECG. It was
      also inferior to a combination strategy, using all 4 markers tested (risk ratio
      2.37, 95% CI 1.44-3.91, P <.001). Fifty of 428 patients (12%) with a cardiac
      troponin I level < or =0.2 ng/mL and 25 of 287 patients (9%) without elevation of
      any marker tested sustained an adverse event during follow-up. CONCLUSIONS:
      Cardiac troponin I is the most useful single biochemical predictor of long-term
      outcome, but the best determinants are age, an abnormal presenting ECG, and an
      "any marker positive" strategy. Patients without elevated cardiac markers have an
      adverse event rate of approximately 10% in the subsequent 31 months.

PMID- 12514660
TI  - Relationship between initial white blood cell counts, stage of acute myocardial
      infarction evolution at presentation, and incidence of Thrombolysis In Myocardial
      Infarction-3 flow after streptokinase.
AB  - BACKGROUND: The initial white cell counts in patients with acute myocardial
      infarction (AMI) may reflect the stage of AMI evolution, and may also be related
      to the efficacy of thrombolytic agents in recanalizing occluded epicardial
      arteries. METHODS: In 312 patients with a first AMI, we divided the initial white
      cell counts into quartiles and investigated their relationship with the time to
      treatment and the incidence of Thrombolysis In Myocardial Infarction (TIMI)-3
      flow at 90 minutes after commencement of streptokinase. RESULTS: A longer time
      from symptom onset to treatment was independently associated with a higher
      neutrophil count and a lower non-neutrophil count. These times were 2.6, 2.9, and
      3.8 hours, respectively, in the lowest, combined second and third (ie, middle),
      and highest neutrophil quartiles (P =.003), and 4.3, 3, and 1.9 hours,
      respectively, in the lowest, combined middle, and highest non-neutrophil
      quartiles (P <.0001). TIMI-3 flow was achieved in 44% of the lowest total white
      cell quartile, 41% of the combined middle quartile, and 60% of the highest
      quartile (P =.05). The corresponding figures were 47%, 49%, and 46% (P =.657) for
      the neutrophil quartiles, and 32%, 46%, and 68% for the non-neutrophil quartiles
      (P =.001). On multivariable analysis, the incidence of TIMI-3 flow was
      independently and positively associated with the initial non-neutrophil count.
      Patients with non-neutrophil counts in the highest quartile had a higher
      incidence of TIMI-3 flow than those in the lowest quartile (odds ratio 2.86, 95%
      CI 1.32-6.23, P =.008). CONCLUSIONS: A longer time from symptom onset to
      thrombolysis for AMI is associated with a higher neutrophil count and a lower non
      neutrophil count at presentation. A higher neutrophil count is not associated
      with worse epicardial blood flow at 90 minutes after streptokinase, and a higher
      non-neutrophil count predicts a greater likelihood of achieving TIMI-3 flow.

PMID- 12514661
TI  - High triglycerides/low high-density lipoprotein cholesterol, ischemic
      electrocardiogram changes, and risk of ischemic heart disease.
AB  - BACKGROUND: High triglycerides (TG)/low high-density lipoprotein cholesterol (HDL
      C)(TG > or =1.60 and HDL-C < or =1.18 mmol/L) and ischemic ST-T changes in the
      resting electrocardiogram (ECG) are both strong risk factors of ischemic heart
      disease (IHD) in men without clinical cardiovascular diseases. This study tested
      the hypothesis that men free of clinical IHD with high TG/low HDL-C and resting
      ischemic ECG changes would have a particularly poor prognosis with respect to
      IHD. METHODS: We conducted a cohort study of 2906 men, aged 53 to 74 years,
      without overt IHD at baseline. RESULTS: During 8 years, IHD developed in 229 men;
      61 cases were fatal. Of the risk factors recorded, ischemic ECG changes and high
      TG/low HDL-C were the strongest risk factors of IHD. Compared with men without
      high TG/low HDL-C and without ischemic ECG changes, age-adjusted relative risk of
      total IHD (95% CI) was 3.5 (1.7-7.2) in men with both high TG/low HDL-C and
      ischemic ECG changes; the corresponding value for fatal IHD was 11.2 (4.9-25.8).
      Adjusted for conventional risk factors, the interaction term high TG/low HDL-C x
      ischemic ECG changes was a significant predictor of IHD death, with a relative
      risk of 2.6 (1.0-6.9). CONCLUSIONS: In men free of clinical IHD, ischemic ECG
      changes were significantly more predictive of fatal IHD in men with high TG/low
      HDL-C, indicating an adverse synergistic effect of these 2 risk factors.

PMID- 12514662
TI  - Direct comparison of characteristics, treatment, and outcomes of patients
      enrolled versus patients not enrolled in a clinical trial at centers
      participating in the TIMI 9 Trial and TIMI 9 Registry.
AB  - BACKGROUND: Questions about the generalizability of randomized trial results to
      clinical practice have arisen because the overall mortality rate is generally
      lower in trials, potentially because patients who are at lower risk are enrolled.
      However, little is known about the characteristics of patients included in
      clinical trials versus those who are not included. METHODS: The Thrombolysis In
      Myocardial Infarction (TIMI) 9 Registry prospectively evaluated patients with ST
      elevation myocardial infarction at 20 hospitals during the TIMI 9 trial, which
      compared hirudin versus heparin with fibrinolysis. We compared the
      characteristics, treatment, and outcomes of patients enrolled in TIMI 9B (n =
      3002) with other fibrinolytic-eligible patients not enrolled in TIMI 9B (n = 296)
      and with those not eligible for fibrinolysis by American College of
      Cardiology/American Heart Association criteria, at the same centers (n = 282),
      with the latter groups divided by use of reperfusion therapy. RESULTS: Across the
      groups, ranging from those in the TIMI 9 trial to those ineligible for
      fibrinolysis, we observed a gradient of higher-risk baseline characteristics,
      lower use of reperfusion therapy, and higher mortality rates (P <.001). In
      addition, comparing fibrinolytic-eligible patients in TIMI 9B versus those not
      enrolled in the trial, the use of aspirin, beta-blockers, and angiotensin
      converting enzyme inhibitors was significantly higher in the TIMI 9B trial.
      Ineligible patients not treated with reperfusion therapy had much lower rates of
      use of these medications and the highest inhospital mortality rate (24%, adjusted
      odds ratio 2.8, P <.0001) CONCLUSIONS: In this prospective registry, patients not
      enrolled in a clinical trial had higher risk characteristics and worse outcomes;
      however, they also were treated less frequently with guideline-recommended
      medications, which may have contributed to their higher mortality rates.

PMID- 12514663
TI  - Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting
      stenosis after myocardial infarction.
AB  - BACKGROUND: Although inherited thrombophilias are more common in patients with
      venous thromboembolism, their influence on the development of myocardial
      infarction (MI) requires clarification. METHODS AND RESULTS: To determine whether
      there are increased frequencies of mutations/polymorphisms in 14 genes
      potentially causing thrombophilia in patients with no flow-limiting stenoses
      after MI compared with patients with > or =1 flow-limiting stenosis of >50%, we
      studied 395 patients (60 with no flow-limiting stenosis) who underwent
      angiography at approximately 1 month. The mutations/polymorphisms studied
      included Factor V Leiden, prothrombin variant G20210A, beta-fibrinogen 448 (G/A),
      endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate
      reductase 677 (C/T), platelet glycoprotein IIIa PlA1/A2, plasminogen activator
      inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282
      (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of
      NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion
      polymorphism. The frequencies of Factor V Leiden and the beta-fibrinogen 448 A
      allele were higher in patients with no flow-limiting stenosis than in patients
      with > or =1 stenosis (11.7% vs 3.6%, odds ratio [OR] 3.6, 95% CI 1.3-9.4, P
      =.015; and 42% vs 27%, OR 2.0, 95% CI 1.1-3.5, P =.018, respectively), and there
      was a trend toward an increased frequency of prothrombin variant G20210A (6.7% vs
      2.1%, OR 3.4, 95% CI 0.95-11.8, P =.069). However, in patients with no flow
      limiting stenosis after MI the frequencies of the other gene
      mutations/polymorphisms were not increased. Also, there were no significant
      interactions between any of these 14 mutation/polymorphisms, major cardiovascular
      risk factors, and the absence of any flow-limiting stenosis, except for Factor V
      Leiden and hypertension (OR 6.34, 95% CI 2.67-100, P =.004). CONCLUSIONS:
      Patients with no flow-limiting stenosis after MI had increased frequencies of 2
      inherited thrombophilias (Factor V Leiden and beta-fibrinogen 448 A allele), and
      there was a trend toward an increased frequency of prothrombin variant G20210A
      compared with patients with > or =1 stenosis. These data suggest that
      polymorphisms/mutations in some gene products influencing coagulation may
      influence the pathogenesis of MI.

PMID- 12514664
TI  - Association of the ScaI atrial natriuretic peptide gene polymorphism with
      nonfatal myocardial infarction and extent of coronary artery disease.
AB  - BACKGROUND: There is growing evidence from recent studies that atrial natriuretic
      peptide (ANP) plays an important part in coronary blood flow regulation and in
      atherosclerosis. Transition T2238-->C in the atrial natriuretic peptide (ANP)
      precursor gene, which leads potentially to the translation of ANP with 2
      additional arginines, has been suggested to be associated with salt-sensitive
      hypertension. According to our knowledge, this study is the first to look for the
      potential association of the ScaI ANP gene polymorphism with the history of
      nonfatal myocardial infarction and the extent of coronary artery disease (CAD).
      METHODS: The study was performed in 847 consecutive, white patients (719 men and
      128 women) with significant coronary artery stenosis confirmed by means of
      elective coronary angiography (at least 1 coronary artery with > or =50% lumen
      narrowing). Screening for the T2238-->C substitution was performed by means of
      polymerase chain reaction of genomic DNA, followed by ScaI digestion and agarose
      gel electrophoresis. RESULTS: We found a significant association of the A2A2 ScaI
      ANP genotype with a higher incidence of positive history of nonfatal myocardial
      infarction (odds ratio 1.85, 95% CI 1.33-2.58) and multiple-vessel CAD (odds
      ratio 1.45, 95% CI 1.02-2.06). The ScaI ANP genotype distribution did not differ
      with age, sex, body mass index, plasma lipids, hypertension, diabetes mellitus,
      and family history of CAD in studied groups. CONCLUSIONS: Our results suggest
      that the ScaI ANP polymorphism may be associated with nonfatal myocardial
      infarction and the extent of CAD. However, the precise mechanism of this
      association remains to be determined.

PMID- 12514665
TI  - Prognostic value of QT interval and QT dispersion in patients with left
      ventricular systolic dysfunction: results from a cohort of 2265 patients with an
      ejection fraction of < or =40%.
AB  - BACKGROUND: Increased QT interval and QT dispersion have been associated with
      higher mortality in population-based studies and in patients with myocardial
      infarction. However, the prognostic significance of these measurements in
      patients with left ventricular (LV) systolic dysfunction is not clear. METHODS
      AND RESULTS: Rate corrected QT interval (QTc) and QT dispersion (QTd) were
      measured by means of an automated method from digitized echocardiograms in 2265
      patients with an LV ejection fraction < or =40% and were related to survival.
      Increased QTc was strongly related to mortality in the whole group and in subsets
      on the basis of age and the level of LV systolic dysfunction. There was a graded
      increase in mortality rate with an increase in QTc. The effect of QTc on
      mortality was incremental to the effects of age and ejection fraction. QT
      interval was measurable in > or =6 leads in 1193 patients in whom QTd was
      computed. QTd higher than the mean value of 35 ms was associated with an increase
      in all cause mortality (P =.04). Its mortality impact was most pronounced in the
      older patients, patients with more severe LV dysfunction, and patients with
      increased QTc. CONCLUSIONS: Both QTc prolongation and increased QTd are
      associated with higher mortality rate in patients with moderate and severe LV
      dysfunction.

PMID- 12514666
TI  - Prevalence and prognostic value of exercise-induced ventricular arrhythmias.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence and
      prognostic significance of exercise-induced ventricular arrhythmias (EIVAs) in
      patients referred for exercise testing, considering the arrhythmic substrate and
      exercise-induced ischemia. BACKGROUND: EIVAs are frequently observed during
      exercise testing, but their prognostic significance is uncertain. The design of
      this study was a retrospective analysis of prospectively collected data, and it
      took place in 2 university-affiliated Veterans Affairs Medical Centers. Patients
      comprised 6213 consecutive males referred for exercise tests. We measured
      clinical exercise test responses and all-cause mortality after a mean follow-up
      of 6 +/- 4 years. EIVAs were defined as frequent premature ventricular
      contractions (PVCs) constituting >10% of all ventricular depolarizations during
      any 30 second electrocardiogram recording, or a run of > or =3 consecutive PVCs
      during exercise or recovery. RESULTS: A total of 1256 patients (20%) died during
      follow-up. EIVAs occurred in 503 patients (8%); the prevalence of EIVAs increased
      in older patients and in those with cardiopulmonary disease, resting PVCs, and
      ischemia during exercise. EIVAs were associated with mortality irrespective of
      the presence of cardiopulmonary disease or exercise-induced ischemia. In those
      without cardiopulmonary disease, mortality differed more so later in follow up
      than earlier. In those without resting PVCs, EIVAs were also predictive of
      mortality, but in those with resting PVCs, poorer prognosis was not worsened by
      the presence of EIVAs. CONCLUSIONS: Exercise induced ischemia does not affect the
      prognostic value of EIVAs, whereas the arrhythmic substrate does. EIVAs and
      resting PVCs are both independent predictors of mortality after consideration of
      other clinical and exercise-test variables. These findings are of limited
      clinical significance because of the modest change in risk and the lack of any
      established intervention. However, they explain some of the previous controversy
      and highlight the need to consider resting PVCs and follow-up duration in
      assessing the clinical implications of EIVAs.

PMID- 12514667
TI  - Prognostic importance of systolic and diastolic function after acute myocardial
      infarction.
AB  - BACKGROUND: Although risk stratification after acute myocardial infarction (AMI)
      often is focused on systolic left ventricular (LV) function, it appears that a
      more complete study of ventricular function including assessment of LV filling
      would be useful. Doppler echocardiography allows assessment of LV filling, and
      with the use of the Tei index (sum of isovolumic relaxation and contraction times
      divided by ejection time), a global estimate of ventricular function may be
      obtained. Therefore, the aim of this study was to determine the prognostic
      importance of LV systolic, diastolic, and overall LV function in a large
      consecutive population with AMI. METHODS: Echocardiography was performed within 6
      days of AMI. LV systolic, diastolic, and global function was assessed by means of
      wall motion index (WMI), mitral flow pattern, and Tei index. The primary end
      point was all-cause death. RESULTS: Of 799 enrolled patients, 197 died during a
      median follow-up of 34 months. In a multivariate model including WMI and clinical
      parameters, WMI had important prognostic information. When mitral filling pattern
      and quartiles of Tei index were added to the model, restrictive filling (mitral
      deceleration time <140 ms) was associated with a risk ratio of 1.9 (95% CI 1.3
      2.7, P <.0001, Tei index values of >0.68/0.56-0.68/0.46-0.55/<0.46 were
      associated with risks of 4.0 [2.1-6.9]/2.3 [1.5-3.9]/2.1 [1.2-3.6]/1.0, P <.001).
      In this model, WMI had no prognostic value (P =.18). CONCLUSIONS: Mitral
      deceleration time and the Tei index have independent and important prognostic
      value after AMI.

PMID- 12514668
TI  - Flow volume asymmetry in the right aortic arch in children with magnetic
      resonance phase encoded velocity mapping.
AB  - BACKGROUND: The right aortic arch is not uncommon in pediatrics. Flow dynamics in
      this type of aortic arch, which is important for cardiac energetics, organ
      perfusion, and Doppler flow calculations, have not been defined. Although there
      are complex secondary flow patterns, bulk axial flow makes up most of the energy
      use. METHODS: We examined 14 children with a right aortic arch by using through
      plane phase-encoded magnetic resonance velocity mapping in the ascending and
      descending aorta to determine flow volume symmetry and velocity. The aortic cross
      section was divided into 4 quadrants aligned along the long axis of the aorta.
      Significance was defined as a P value <.05. RESULTS: In the ascending aorta, the
      posterior right quadrant demonstrated significantly greater blood flow than the
      other quadrants across the entire cardiac cycle (28% vs 23%-25%) and at the point
      of maximum flow (29% vs 22%-25%). Flow asymmetry was also present in the
      descending aorta; there was significantly more flow in the posterior quadrants
      than the anterior quadrants in total flow across the cardiac cycle (28% vs 21%
      23%) and at the point of maximum flow (27%-28% vs 20%-24%). The time to maximum
      flow was significantly shorter in the ascending than the descending aorta (18% vs
      24% of the cardiac cycle). In 10 of 14 patients, maximum velocity occurred in the
      right half of both the ascending and descending aorta. Flow reversal at end
      systole was haphazard, occurring in all quadrants. CONCLUSION: Flow volume
      asymmetry exists in the ascending and descending portions of the right aortic
      arch, which has implications for cardiac energetics, organ perfusion, and Doppler
      scanning flow calculations. This information may be useful in designing improved
      aortic surgical reconstructions in cases of congenital heart disease.

PMID- 12514669
TI  - Effect of infarcted myocardium on diagnostic accuracy of exercise
      echocardiography for detecting noninfarct-related coronary artery lesions.
AB  - BACKGROUND: The utility of exercise echocardiography for evaluating remote
      ischemia due to noninfarct-related artery (n-IRA) lesions in patients with prior
      myocardial infarction has not been established. METHODS: Quantitative coronary
      angiography and treadmill exercise echocardiography were performed within 2 weeks
      in 115 patients with prior myocardial infarction (>6 weeks) and 224 patients
      without myocardial infarction. Coronary lumen diameter stenosis > or =50% (by
      angiography) and the lack of a hyperdynamic response on exercise echocardiography
      were considered significant. Myocardial infarction size was defined as the number
      of myocardial segments with severe hypokinesis, akinesis, or dyskinesis on
      echocardiography at rest. RESULTS: For detection of n-IRA lesions in patients
      with prior myocardial infarction, the sensitivity of exercise echocardiography
      was similar (78% vs 79%, P = not significant), however, the specificity was
      significantly lower (77% vs 91%, P <.01) than for detection of significant
      stenoses in patients without prior myocardial infarction. Angiographic percent
      diameter stenosis, presence of collateral vessel, achieved exercise level, and
      presence of peri-infarct ischemia did not affect the specificity of exercise
      echocardiography. However, the specificity of exercise echocardiography was
      significantly lower (69% vs 84%, P <.05) in patients with echocardiographically
      large infarction (infarction size > or =2) than in patients with small infarction
      (infarction size <2). CONCLUSION: In patients with prior myocardial infarction,
      exercise echocardiography showed low specificity for detection of noninfarct
      related artery lesions, especially in patients with echocardiographically large
      myocardial infarction. These characteristics of treadmill exercise
      echocardiography should be considered when this technique is applied for patients
      with healed myocardial infarction.

PMID- 12514670
TI  - Association between angiotensin I-converting enzyme gene insertion/deletion
      polymorphism and mitral valve prolapse syndrome.
AB  - BACKGROUND: Some studies have reported that patients with mitral valve prolapse
      syndrome (MVPS) also have a disorder in the autonomic or neuroendocrine function,
      which can cause a host of related symptoms. A potential role of the renin
      angiotensin system in the pathogenesis of MVPS has been addressed. However, the
      role of angiotensin I-converting enzyme (ACE) genetic variant in MVPS has not
      been studied. We therefore performed a case-control study investigating the
      possible relation between ACE gene polymorphisms and MVPS in Taiwan Chinese.
      METHODS: We studied 100 patients with MVPS diagnosed by echocardiography and 100
      age- and sex-matched normal control patients. ACE gene insertion/deletion (I/D),
      A-240T, and G2350A polymorphisms were identified by polymerase chain reaction
      based restriction analysis. RESULTS: There was a significant difference in the
      distribution of ACE I/D genotypes (P =.003) and allelic frequencies (P =.001)
      between MVPS cases and control patients. An odds ratio for the risk of MVPS
      associated with the ACE II genotype was 2.14 (95% CI 1.20-3.80 ). An odds ratio
      for the risk of MVPS associated with ACE I allele was 1.96 (95% CI 1.30-2.97).
      The A-240T and G2350A polymorphisms of the ACE gene showed no association with
      MVPS (P =.20, P =.13, respectively). CONCLUSIONS: This study showed that patients
      with MVPS have a higher frequency of ACE II genotype, which supports a role of
      the ACE I/D gene polymorphism in determining the risk of MVPS among the Chinese
      population in Taiwan.

PMID- 12514671
TI  - Left Atrial Appendage Occlusion Study (LAAOS): a randomized clinical trial of
      left atrial appendage occlusion during routine coronary artery bypass graft
      surgery for long-term stroke prevention.
AB  - BACKGROUND: Many patients undergoing coronary artery bypass graft (CABG) surgery
      have risk factors for both atrial fibrillation (AF) and stroke. The left atrial
      appendage (LAA) is a main source of thrombus coming from the left atrium. LAA
      occlusion should be tested as a means to reduce future cerebral ischemic events
      in these patients. METHODS: The Left Atrial Appendage Occlusion Study (LAAOS) is
      a randomized clinical trial designed to evaluate the feasibility, safety, and
      efficacy of LAA occlusion for prevention of ischemic stroke in patients
      undergoing CABG. The target population consists of patients at risk of AF and
      stroke who are having routine CABG surgery. The main study will be a prospective,
      controlled, unblinded trial. Patients at risk of future development of AF, or
      having AF, will be randomly assigned to undergo or not undergo LAA occlusion. A
      total of 2500 patients will be randomly assigned and followed for 5 years for the
      primary outcome of stroke. This study of 2500 patients will have 90% power to
      detect a relative reduction of 20% in stroke, from a 5-year incidence of 20% in
      the control group to 16% in the intervention group. Currently, a pilot trial is
      underway that will enroll 100 patients to assess feasibility, safety, and rates
      of successful LAA occlusion as assessed by postoperative transesophageal
      echocardiography. The most suitable surgical technique will also be assessed
      during the pilot trial. In the pilot study, the main outcomes are safety and rate
      of successful obliteration of the LAA after surgical occlusion. CONCLUSIONS: The
      clinical trial designed to evaluate LAA occlusion at the time of routine CABG
      surgery is currently in the pilot phase.

PMID- 12514672
TI  - Rationale for use of an exercise end point and design for the ADVANCE (A Dose
      evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise)
      trial.
AB  - BACKGROUND: Exercise intolerance is a primary characteristic of chronic
      congestive heart failure. Exercise testing is therefore widely used to evaluate
      the degree of functional impairment, prognosis of underlying cardiac disease, and
      response to treatment. Historically, studies that used exercise tolerance as an
      end point to evaluate the efficacy of pharmacologic interventions have been
      confounded by methodologic differences involving protocols, exercise end points,
      absence or misuse of gas exchange data, and study design. METHODS: The purpose of
      this study was to outline the methodology and rationale of a unique
      cardiopulmonary exercise trial. The design was based on prior experience from
      evaluation of ACE inhibitors and other interventions. The ADVANCE (A Dose
      evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial
      is a multicenter, double-blind, placebo-controlled, randomized trial
      investigating the effects of a vasopressin antagonist, conivaptan, on functional
      capacity in patients with heart failure. RESULTS: The primary end point is change
      in the exercise time to reach 70% of peak oxygen consumption during an
      incremental exercise test. Secondary end points include changes in peak oxygen
      consumption and other exercise parameters as well as quality-of-life indicators.
      The study incorporates several unique features to lessen potential methodological
      errors of exercise testing in heart failure, including use of a core laboratory
      to evaluate exercise tests, a computer program to determine the exercise end
      points, and validation of each site before patient enrollment. CONCLUSIONS: The
      results of this study will have value not only for the further use of vasopressin
      antagonists for heart failure therapy but also for the use of exercise testing
      and gas exchange determination for the evaluation of new drug therapies.

PMID- 12514673
TI  - Randomized, double-blind, placebo-controlled long-term study of isosorbide-5
      mononitrate therapy in patients with left ventricular dysfunction after acute
      myocardial infarction.
AB  - BACKGROUND: Nitrates are often administrated with a variety of other
      pharmacologic agents in the management of chronic heart failure (CHF). However,
      limited information is available concerning the long-term effects in patients
      with evidence of left ventricular (LV) dysfunction after acute myocardial
      infarction (AMI) already treated with standard heart failure therapy. METHODS: In
      a randomized, double-blind, placebo-controlled trial, we evaluated the effects of
      a 60 mg dose of isosorbide-5-mononitrate (IS-5-MN) given daily for 11 months to
      47 patients with clinical or echocardiographic evidence of left ventricular
      dysfunction after acute myocardial infarction. Forty-five patients received a
      placebo. RESULTS: Invasive hemodynamic measurements did not show any difference
      between the treatment regimens. Overall changes in echocardiographic measurements
      were not significantly different between IS-5-MN therapy and the placebo groups.
      However, in a prespecified subgroup with left ventricular ejection fraction < or
      =40% at baseline, IS-5-MN therapy resulted in a lesser increase of end-diastolic
      volume index than the placebo (P =.047). IS-5-MN significantly reduced the serum
      concentration of atrial natriuretic peptide (mean 20.0 pmol/L, 95% CI 7.7-32.3, P
      =.002), whereas the placebo did not (P =.041 for the difference between the
      groups). The proportion of patients taking diuretics was significantly reduced in
      the IS-5-MN group, from 30 of 44 to 20 of 44 (P =.02), but not with placebo,
      which remained at 27 of 43 (P = 1.0, with P =.048 for the difference between the
      regimens). CONCLUSIONS: Oral, long-term IS-5-MN therapy resulted in lower atrial
      natriuretic peptide levels and reduced the need for additional diuretics. Less LV
      dilatation was observed in patients with more severe LV dysfunction at baseline.

PMID- 12514674
TI  - Reduction of oxidative stress augments natriuretic effect of furosemide in
      moderate heart failure.
AB  - BACKGROUND: The significance of antioxidant therapy in heart failure has not been
      fully examined. This study evaluated whether vitamin C has beneficial effects on
      renal function or augments the renal effects of furosemide in patients with heart
      failure. METHODS: There were 2 protocols. In protocol 1, plasma level of
      thiobarbituric acid-reactive substances (TBARS) and renal function were assessed
      before and after intravenous infusion of vitamin C or placebo in 8 patients with
      moderate congestive heart failure (CHF) treated with enalapril. In protocol 2, a
      randomized crossover study was performed in patients with moderate CHF treated
      with either an ACE inhibitor (enalapril) (n = 10) or an angiotensin II receptor
      antagonist (losartan) (n = 9) and in asymptomatic patients with impaired left
      ventricular function treated with enalapril (n = 8). TBARS and renal function
      were assessed before and after intravenous infusion of furosemide alone,
      coinfusion of furosemide with placebo and vitamin C, or coinfusion of furosemide
      with vitamin C and a kallikrein inhibitor (nafamostat mesilate). RESULTS: In
      protocol 1, although vitamin C reduced TBARS, it did not affect renal function.
      In protocol 2, TBARS was higher in patients with moderate CHF than in
      asymptomatic patients. Vitamin C augmented natriuretic effect of furosemide (from
      179 +/- 98 to 192 +/- 104 micromol/min, P <.01) only in patients with moderate
      CHF treated with enalapril but not in the other 2 groups. Nafamostat mesilate
      prevented this augmentation. CONCLUSIONS: In patients with CHF treated with
      enalapril, counteraction of the increased oxidative stress by vitamin C may
      contribute to the augmented natriuretic effect of furosemide through the renal
      kinin-nitric oxide pathway.

PMID- 12514675
TI  - Home-based versus hospital-based exercise programs in patients with coronary
      artery disease: effects on coronary vasomotion.
AB  - BACKGROUND: In a randomized study, we recently documented that a vigorous,
      hospital-based exercise training (ET) program improves coronary endothelial
      function in coronary artery disease. The aim of this consecutive study was to
      assess whether a home-based exercise program with reduced average training
      duration can sustain previously achieved effects on coronary endothelial
      function. METHODS: Nineteen patients with coronary endothelial dysfunction
      documented by acetylcholine-induced vasoconstriction were randomly assigned to a
      training group (n = 10) or a control group (n = 9). After 4 weeks of inhospital
      training (60 min of bicycle ergometry per day), all training patients were
      enrolled in a 5-month home-based program of 20 minutes' ergometry training per
      day and 1 group training session per week. At baseline, after 4 weeks and 6
      months, endothelium-mediated vasodilation was assessed by quantitative coronary
      angiography after intracoronary infusions of acetylcholine. Average peak velocity
      (APV) was measured with a Doppler wire. Coronary blood flow (CBF) was calculated
      by multiplying vascular cross-sectional area and APV. RESULTS: CBF increased in
      response to 7.2 microg/min acetylcholine, from 27% +/- 11% at the beginning of
      the study to 110% +/- 24% after 4 weeks (P <.01 vs control group). After 6
      months, the increase in CBF was lower versus inhospital training (67% +/- 18%, P
      <.05 vs 4 weeks). Changes in APV between 1 and 6 months correlated with daily
      training durations (r = 0.65, P =.03). CONCLUSIONS: Home-based ET sustained part
      of the effects of hospital-based ET on endothelium-dependent vasodilation in
      coronary artery disease. However, acetylcholine-induced increases in CBF were
      lower after home-based ET, suggesting a relation between daily training duration
      and improvement of coronary vasomotion.

PMID- 12514676
TI  - Effect of current federal regulations on handgun safety features.
AB  - STUDY OBJECTIVE: In the late 1960s, the Bureau of Alcohol, Tobacco, and Firearms
      implemented the "factoring criteria," a set of minimum size and safety standards
      required for any handgun imported into the United States. These standards,
      however, were not applied to guns manufactured domestically. We determine whether
      extending the factoring criteria to all handguns sold in the United States, as
      has been proposed in Congress, would increase the likelihood that safety devices
      would be included in new handgun designs. METHODS: Imported and domestic handgun
      models produced in 1996 were examined to determine the prevalence of 4 passively
      acting safety devices on pistols and 1 passive safety device on revolvers.
      Domestic models were also scored against the factoring criteria. RESULTS:
      Compared with domestic pistol models, imported pistols were more likely to
      include a firing pin block (odds ratio [OR] 2.43; 95% confidence interval [CI]
      1.54 to 3.85) and a loaded chamber indicator (OR 1.59; 95% CI 0.98 to 2.56).
      Domestic pistol models that already met the factoring criteria were more likely
      to include a loaded chamber indicator (OR 12.05; 95% CI 2.74 to 53.02), a grip
      safety (OR 24.12; 95% CI 7.8 to 74.33), and a firing pin block (OR 4.92; 95% CI
      2.35 to 10.29) than domestic models that did not meet the criteria. CONCLUSION:
      Although pistol models that meet the factoring criteria are more likely to
      contain safety devices than those that do not, the net effect is modest. Thus,
      the factoring criteria alone are insufficient to ensure consistent incorporation
      of safety features into new handgun designs.

PMID- 12514677
TI  - Unintended shootings in a large metropolitan area: an incident-based analysis.
AB  - STUDY OBJECTIVE: We determine the proportion of unintended shootings that might
      be prevented by promoting safe storage, safe handling, and/or safer firearm
      designs. METHODS: A regional firearm injury surveillance system was used to
      identify fatal and nonfatal unintentional shootings in a 5-county metropolitan
      area. Case reports were reviewed, and the causes of each shooting were
      independently classified by 4 members of the research team. A consensus
      conference was held to resolve disagreements. RESULTS: Between May 1, 1996, and
      June 30, 2000, 216 cases of unintentional firearm injury were identified, 3.8% of
      the shootings documented during the study period. Six (2.8%) were fatal. The
      majority of victims were between 15 and 34 years of age. One fourth (54) of the
      shootings involved victims younger than 18 years. Handguns were involved in 87%
      of the incidents. Enough information was available to characterize the incident
      in 122 (57%) cases. All but 6 fell into 1 or more of 3 broad categories of
      causation: Child access (14%), mishandling (74%), and/or deficiencies in firearm
      design (32%). CONCLUSION: Many unintentional shootings could be prevented by
      promoting safe storage of guns in the home, promoting safe handling of firearms,
      and requiring that all new handguns incorporate basic safety features.

PMID- 12514678
TI  - Facial trauma and the risk of intracranial injury in motorcycle riders.
AB  - STUDY OBJECTIVE: We describe the associations among facial fracture, helmet use,
      skull fracture, and traumatic brain injury in injured motorcycle riders. METHODS:
      The study population consisted of 5,790 motorcycle riders who sustained an injury
      from a crash in 1991, 1992, or 1993 and were identified from emergency department
      or hospital records in 28 hospitals in 11 California counties. Diagnostic
      information was abstracted from ED or hospital records and coded to the 1990
      Abbreviated Injury Scale. The risk of traumatic brain injury was examined by
      using odds ratios and 95% confidence intervals. Logistic regression analysis was
      used to examine the associations among helmet use, skull fracture, facial
      fracture, and traumatic brain injury. RESULTS: Facial injury was diagnosed in
      24.4% of all injured riders, including 411 with one or more facial fractures. The
      odds of traumatic brain injury were 3.5 times greater with than without a facial
      injury and 6.5 times greater with a facial fracture than with no facial injury.
      Significantly increased odds of traumatic brain injury were observed for fracture
      of all bones of the face, but the highest odds of traumatic brain injury were
      found in riders with fractures to bones of the upper face. Helmet use status and
      the presence of skull fracture were found to be significant effect modifiers.
      Facial fracture with concurrent skull fracture increased the risk of traumatic
      brain injury dramatically. Facial fractures are more strongly associated with
      traumatic brain injury in helmeted riders. CONCLUSION: The presence of facial
      fractures increases the risk of traumatic brain injury. Riders with facial
      fractures should be screened for brain injury, regardless of helmet use status.

PMID- 12514679
TI  - Bilateral sixth nerve palsy after head trauma.
AB  - Gaze deficits are not uncommon after head trauma and might be caused by injury to
      the central nervous system, the peripheral nerve, or the motor unit. Traumatic
      bilateral sixth cranial nerve palsies are a rare condition and are typically
      associated with additional intracranial, skull, and cervical spine injuries. We
      describe a case of a complete bilateral sixth nerve palsy in a 44-year-old male
      patient with trauma with no intracranial lesion, no associated skull or cervical
      spine fracture, and no altered level of consciousness. The emergency physician
      should be aware of the differential diagnosis, initial workup, and injuries
      associated with a traumatic gaze deficit.

PMID- 12514680
TI  - Policy and technology for safer guns: an update.

PMID- 12514681
TI  - Waiting times in California's emergency departments.
AB  - STUDY OBJECTIVE: Many perceive emergency department crowding as a significant
      problem that is getting worse. A national survey of ED directors defined
      crowding, in part, as waiting more than 1 hour to see a physician, a wait
      considered likely to result in adverse outcomes. Yet few data are available on ED
      waiting times among a heterogeneous group of hospitals serving a distinct
      geographic region. METHODS: We observed a random sample of 1,798 patients
      visiting 30 California EDs between December 15, 2000, and May 15, 2001. We
      defined waiting time as the interval from ED arrival to first contact with a
      physician or midlevel provider. RESULTS: Patients waited an average of 56 minutes
      (95% confidence interval [CI] 52 to 61 minutes; median 38 minutes); 42% waited
      longer than 60 minutes. Ordinary least squares regression analysis revealed that
      waiting times were significantly longer at hospitals in poorer neighborhoods: For
      every 10,000 dollars decline in per capita income, patients waited 10.1 minutes
      longer (95% CI 1.8 to 18.4 minutes; P=.02) after adjusting for hospital
      ownership, teaching status, trauma status, proximity to a recently closed ED, ED
      volume, patient severity, and age. Lower ratios of physicians and triage nurses
      to waiting room patient were also associated with longer waits. CONCLUSION:
      Waiting times often exceeded the threshold set by a survey of ED directors.
      Further study is required to examine factors that lead to longer waiting times at
      hospitals in low-income areas. Physician and nurse staffing should be
      investigated as a means of reducing waiting times.

PMID- 12514682
TI  - Cost-effectiveness of a brief two-stage emergency department intervention for
      high-risk elders: results of a quasi-randomized controlled trial.
AB  - STUDY OBJECTIVE: : We determine the cost-effectiveness of a 2-stage emergency
      department intervention in addition to usual ED care compared with that of usual
      care alone. METHODS: The intervention comprises 2 steps: (1) identification of
      high-risk patients by using a screening tool and (2) a brief standardized nursing
      assessment to identify unresolved problems, followed by referral to an
      appropriate community provider. The patient population was composed of
      individuals aged 65 years and older to be released from the EDs of 4 Montreal
      hospitals. Patients were randomized by day of ED visit. The perspective of the
      study is societal, including patients, caregivers, and the formal health care
      (government-funded) system. Outcomes, measured from randomization to 4 months
      after randomization, included (1) functional decline, as measured by an
      activities of daily living instrument, or death, and (2) changes in depressive
      symptoms. Costs include post-ED care, including hospitalization, physician
      services, community care, outpatient drugs, and patient and caregiver costs. Cost
      items were measured with administrative databases and self-reported
      questionnaires. Unit costs for these items were either province-wide rates or
      else were estimated directly by using provider data. Cost-effectiveness is
      assessed in qualitative terms, such that outcomes and costs are compared
      separately. RESULTS: The intervention was associated with a reduced rate of
      functional decline (including death) at 4 months. There was no effect of the
      intervention on change in the patient's depressive symptoms at 4 months relative
      to baseline. The estimated ratio of overall costs per patient in the intervention
      versus the control group, adjusted for covariates, was 0.94 (95% credible
      interval 0.75 to 1.17). Among patients who had visited the ED during the 30 days
      before the index visit, the ratio was 0.66 (95% credible interval 0.44 to 0.97).
      CONCLUSION: In this study setting, the intervention is preferred over usual care
      because beneficial functional outcomes were observed, and overall societal costs
      were no higher than if usual care only was given.

PMID- 12514683
TI  - Case finding and referral model for emergency department elders: a randomized
      clinical trial.
AB  - STUDY OBJECTIVE: Elderly emergency department patients have complex medical needs
      and limited social support. A transitional model of care adapted from hospitals
      was tested for its effectiveness in the ED in reducing subsequent service use.
      METHODS: A randomized clinical trial was conducted at 2 urban, academically
      affiliated hospitals. Participants were 650 community-residing individuals 65
      years or older who were discharged home after an ED visit. Main outcomes were
      service use rates, defined as repeat ED visits, hospitalizations, or nursing home
      admissions, and health care costs at 30 and 120 days. Intervention consisted of
      comprehensive geriatric assessment in the ED by an advanced practice nurse and
      subsequent referral to a community or social agency, primary care provider,
      and/or geriatric clinic for unmet health, social, and medical needs. Control
      group participants received usual and customary ED care. RESULTS: The
      intervention had no effect on overall service use rates at 30 or 120 days.
      However, the intervention was effective in lowering nursing home admissions at 30
      days (0.7% versus 3%; odds ratio 0.21; 95% confidence interval [CI] 0.05 to 0.99)
      and in increasing patient satisfaction with ED discharge care (3.41 versus 3.03;
      mean difference 0.37; 95% CI 0.13 to 0.62). The intervention was more effective
      for high-risk than low-risk elders. CONCLUSION: An ED-based transitional model of
      care reduced subsequent nursing home admissions but did not decrease overall
      service use for older ED patients. Further studies are needed to determine the
      best models of care for this setting and for at-risk patients.

PMID- 12514684
TI  - How do we draw inference from "negative" studies?

PMID- 12514685
TI  - Protecting research subjects under the waiver of informed consent for emergency
      research: experiences with efforts to inform the community.
AB  - STUDY OBJECTIVES: The US Food and Drug Administration (FDA) and Department of
      Health and Human Services created a method for obtaining a waiver of informed
      consent to permit research in emergency settings when patients are not competent.
      One of the requirements to obtain a waiver is public disclosure about the
      research. We describe approaches used to meet the public disclosure requirement.
      METHODS: We performed a qualitative content analysis of the FDA's repository for
      mandatory documentation of public disclosure efforts as of November 1999. Data
      from 4 studies were analyzed: 2 multi-institutional trials involving trauma and 2
      smaller trials involving cardiac arrest. These efforts included both 1-way
      communications, such as announcements, and 2-way communications, such as focus
      groups and public meetings. Participation in and common concerns expressed during
      2-way communications were noted, as was evidence of mechanisms of advance refusal
      and the collection of quantitative data on public opinion. RESULTS: One-way
      communications were the predominant method of disclosure. Many 2-way
      communications were not directed toward lay persons. Those that were often
      involved fewer than 15 participants. Concerns regarding inability to refuse study
      participation, racial biases affecting study design and execution, and ambiguity
      with regard to how community input would be used in study decision making were
      raised in several 2-way communications. A minority of participating hospitals
      announced mechanisms of advance refusal or collected quantitative data on public
      opinion concerning proposed research. CONCLUSION: Initial experience with
      obtaining a waiver of informed consent for emergency research suggests that
      community involvement and specific public concerns should be carefully considered
      in future applications for such a waiver.

PMID- 12514686
TI  - The legacy of the Tuskegee syphilis experiments for emergency exception from
      informed consent.

PMID- 12514687
TI  - Journal policy on ethics in scientific publication.
AB  - Medical journals aspire to select, through peer review, the highest quality
      science, and their reputations depend on the trust of readers, authors,
      researchers, reviewers, and patients. Almost every aspect of this process
      involves important ethical principles and decisions, which are seldom explicitly
      stated and even less often shared with the readership. A comprehensive policy on
      publication ethics is summarized in this article. A few of the topics addressed
      are study design; research subject consent; definitions and responsibilities of
      authorship; declaration of paid writers; types of potential conflicts of
      interest; management of conflicts of interest on the part of authors, journal
      reviewers, and members of the editorial board; blinding and confidentiality of
      peer review; assessment of peer review quality; public identification of degree
      of peer review of various portions of the journal; criteria for manuscript
      decisions; management of author appeals; definitions of prior publication;
      plagiarism; criteria for advertising and relationship between advertising and
      editorial matter; allegations of misconduct and journal policies for responding
      to them; and the relationship of the journal to the sponsoring society. Our goal
      in publishing these policies is to make the guiding ethical principles of this
      journal accessible to all of our readers and contributors.

PMID- 12514688
TI  - Variations among emergency departments in the treatment of benign headache.
AB  - STUDY OBJECTIVE: The practice patterns of US emergency departments in the
      treatment of patients with isolated benign headache have been recently described.
      How treatment varies among EDs has not been reported. To assess institutional
      variability in the pharmacotherapy of patients with benign headache, we describe
      and analyze the practice patterns of 3 US EDs. METHODS: This health records
      survey included a cohort sample of consecutive adult patients aged 16 to 65 years
      treated with parenteral medication for isolated benign headache at 3
      nonaffiliated US EDs: a large, group-model health maintenance organization, a
      tertiary-care academic center, and a rural community hospital. Patients who
      underwent a diagnostic search for intracranial pathology, who had any nonheadache
      secondary diagnosis, or who had coexistent trauma, fever (temperature of > or
      =38.0 degrees C [100.4 degrees F]), or known pregnancy were excluded from study
      analysis. Demographic, clinical, and pharmacotherapeutic variables were collected
      for each ED visit. Descriptive analyses were performed; comparisons were made
      with t tests. RESULTS: Of the 490 eligible patients treated during the 4-month
      study period, the mean age was 36.4 years, and 374 (76%) were women. During their
      629 visits, 364 (58%) received a migraine diagnosis, and 258 (41%) received a
      nonspecific headache diagnosis. Polypharmacy was common: 515 (82%) received 2 or
      more medications, and 154 (25%) received 3 or more medications. Pharmacotherapy
      varied greatly among the EDs. Use of opioid agonists showed the widest variation
      (16% to 72%), although use of dihydroergotamine (5% to 16%), prochlorperazine
      (32% to 59%), and adjunct diphenhydramine with prochlorperazine (42% versus 88%)
      also varied. CONCLUSION: Great institutional variability exists among US EDs in
      the parenteral treatment of patients with isolated benign headache.

PMID- 12514689
TI  - Benign exertional headache.
AB  - We describe 4 patients with benign exertional headache presenting to the
      emergency department. Consideration of this uncommon cause of headache might
      facilitate an accurate diagnosis of those patients with headache caused by
      strenuous exercise.

PMID- 12514690
TI  - Late-onset presentation of ornithine transcarbamylase deficiency in a young woman
      with hyperammonemic coma.
AB  - Ornithine transcarbamylase deficiency (OTCD) is an X-linked inherited disease and
      the most common inborn error in urea synthesis in human patients. In adult
      heterozygous patients, OTCD can be responsible for life-threatening
      hyperammonemic coma. We report the case of a 32-year-old woman admitted to our
      hospital with seizures after a recent high protein load. Her parents related a
      history of recurrent episodes of vomiting, meat refusal, lethargy, and
      convulsions since childhood, and measurement of plasma ammonemia levels was the
      key to early diagnosis of OTCD. We report the pathophysiologic characteristics,
      clinical features, clinical course, and differential diagnosis of OTCD and
      discuss the therapeutic options, including continuous venovenous
      hemodiafiltration and pharmacologic therapy for reduction of plasma ammonemia
      levels. A diagnosis of OTCD should be considered in adult nonhepatic patients
      with hyperammonemic coma, particularly if they have a history of protein
      avoidance and neurologic symptoms. Early recognition and appropriate treatment
      are critical to avoid severe brain damage and death.

PMID- 12514691
TI  - Cognitive forcing strategies in clinical decisionmaking.
AB  - Cognitive errors underlie most diagnostic errors that are made in the course of
      clinical decisionmaking in the emergency department. These errors are universal
      and are prevalent in the special milieu of the ED. Their properties appear to be
      distinct from those associated with the performance of procedures. They are often
      costly, but, importantly for both the patient and the physician, they are also
      highly preventable. Recent developments in education theory provide a means for
      minimizing and avoiding diagnostic error. Through the process of metacognition,
      clinicians can develop cognitive forcing strategies to abort such latent errors.
      Three levels of cognitive forcing strategies are described: universal, generic,
      and specific. Specific cognitive forcing strategies provide a formal cognitive
      debiasing approach to deal with what have previously been described as pitfalls
      in clinical reasoning. This metacognitive approach can be taught to practicing
      clinicians and to those in training to inoculate them against making diagnostic
      errors. The adoption of this method provides a systematic approach to cognitive
      root-cause analysis in the avoidance of adverse outcomes associated with delayed
      or missed diagnoses and with the clinical management of specific cases.

PMID- 12514692
TI  - Thinking about thinking.

PMID- 12514693
TI  - Clinical policy: critical issues in the initial evaluation and management of
      patients presenting to the emergency department in early pregnancy.

PMID- 12514694
TI  - Evidence-based emergency medicine. Update: do ophthalmic nonsteroidal anti
      inflammatory drugs reduce the pain associated with simple corneal abrasion
      without delaying healing?
AB  - INTRODUCTION: Some studies have suggested that ophthalmic nonsteroidal anti
      inflammatory drugs (NSAIDs) decrease the pain associated with corneal abrasions
      without impairing healing. This evidence-based emergency medicine (EBEM) critical
      appraisal reviews the literature, including additional studies appearing since
      the publication of an earlier EBEM review in 1999. METHODS: The updated search
      for randomized controlled trials from 1999 to 2002 complemented the previous 1966
      to 1999 search. The methodologic quality of the studies was assessed. Qualitative
      methods were used to summarize the study results. RESULTS: The search identified
      3 studies not included in the previously published review of ophthalmic NSAIDs,
      yielding a total of 5 blinded, randomized, placebo-controlled trials involving
      NSAIDs for corneal abrasions. The methodologic quality of the new studies was
      somewhat higher than that of the 2 original studies and was rated as "good" to
      "strong." The qualitative summary indicates that NSAIDs provide greater pain
      relief and improvement of other subjective symptoms when compared with placebo.
      However, whether the reduction of pain, as measured by visual analog pain scales,
      exceeds the minimal clinically significant difference is equivocal. The use of
      ophthalmic NSAIDs may decrease the need for sedating analgesics. CONCLUSION:
      Ophthalmic NSAIDs appear to be useful for decreasing pain in patients with
      corneal abrasions who can afford the medication and who must return to work
      immediately, particularly where potential opioid-induced sedation is intolerable.

PMID- 12514695
TI  - Evidence-based emergency medicine. Anticoagulation or antiplatelet therapy for
      non-rheumatic atrial fibrillation and flutter.

PMID- 12514696
TI  - International emergency medicine fellowship: the basics.

PMID- 12514697
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention.

PMID- 12514698
TI  - Tough tube.

PMID- 12514700
TI  - Elevated beta-secretase expression and enzymatic activity detected in sporadic
      Alzheimer disease.

PMID- 12514701
TI  - Measuring T-cell-mediated cytotoxicity using antibody to activated caspase 3.

PMID- 12514702
TI  - Test panels no better than internal review.

PMID- 12514703
TI  - Biotech meets NIH to discuss poor disease markets.

PMID- 12514704
TI  - NCI to focus on clinical trial speed.

PMID- 12514705
TI  - Microarray to be used as routine clinical screen.

PMID- 12514706
TI  - Drug costs threaten patent protection.

PMID- 12514707
TI  - Thomas Starzl.

PMID- 12514710
TI  - Immunotherapy for AIDS virus infections: cautious optimism for cell-based
      vaccine.

PMID- 12514711
TI  - Unmet expectations: the brain minds.

PMID- 12514712
TI  - Predicting the future of breast cancer.

PMID- 12514714
TI  - Sensing heart stress.

PMID- 12514715
TI  - Setting the cytokine trap for autoimmunity.

PMID- 12514716
TI  - In vivo imaging reveals estrogen receptor's hidden personality.

PMID- 12514717
TI  - The nucleolus: at the stem of immortality.

PMID- 12514720
TI  - Can needle-free administration of vaccines become the norm in global
      immunization?

PMID- 12514721
TI  - Cell encapsulation: promise and progress.

PMID- 12514722
TI  - The total artificial heart.

PMID- 12514723
TI  - Beyond six colors: a new era in flow cytometry.

PMID- 12514724
TI  - Advances in the use of synthetic combinatorial chemistry: mixture-based
      libraries.

PMID- 12514725
TI  - Shedding light onto live molecular targets.

PMID- 12514726
TI  - Engineered antibodies.

PMID- 12514727
TI  - Ligand-directed targeting of genes to the site of disease.

PMID- 12514728
TI  - Trends in microarray analysis.

PMID- 12514733
TI  - Thymopoiesis independent of common lymphoid progenitors.
AB  - Early T lineage progenitors (ETPs) in the thymus are thought to develop from
      common lymphoid progenitors (CLPs) in the bone marrow (BM). We compared thymic
      ETPs to BM CLPs in mice and found that they differed in several respects. Thymic
      ETPs were not interleukin 7 (IL-7)-responsive and generated B lineage progeny
      with delayed kinetics, whereas BM CLPs were IL-7-responsive and rapidly generated
      B cells. ETPs sustained production of T lineage progeny for longer periods of
      time than BM CLPs. Analysis of Ikaros-deficient mice that exhibit ongoing
      thymopoiesis without B lymphopoeisis revealed near-normal frequencies of thymic
      ETPs, yet undetectable numbers of BM CLPs. We conclude that ETPs can develop via
      a CLP-independent pathway.

PMID- 12514734
TI  - LAB: a new membrane-associated adaptor molecule in B cell activation.
AB  - The adaptor molecule, linker for activation of T cells (LAT), is essential in T
      cell activation and development; a similar molecule in B cells has not yet been
      identified. Here, we report the identification of a new adaptor protein, linker
      for activation of B cells (LAB). Like LAT, LAB was localized to lipid rafts. Upon
      activation via the B cell receptor (BCR), LAB was phosphorylated and interacted
      with the adaptor protein Grb2. Decreased LAB expression led to a reduction in BCR
      mediated calcium flux and Erk activation. LAB rescued thymocyte development but
      not normal T cell activation in LAT(-/-) mice. Our data suggest that LAB links
      BCR engagement to downstream signaling pathways.

PMID- 12514735
TI  - Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney
      cells.
AB  - Several proteins implicated in the pathogenesis of polycystic kidney disease
      (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with
      mutations in TgN737Rpw (encoding polaris). It is not known, however, whether
      ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show
      that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by
      Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD,
      co-distribute in the primary cilia of kidney epithelium. Cells isolated from
      transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+)
      influx in response to physiological fluid flow. Blocking antibodies directed
      against PC2 similarly abolished the flow response in wild-type cells as did
      inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins,
      phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1
      and PC2 contribute to fluid-flow sensation by the primary cilium in renal
      epithelium and that they both function in the same mechanotransduction pathway.
      Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the
      inability of cells to sense mechanical cues that normally regulate tissue
      morphogenesis.

PMID- 12514736
TI  - Ciliary signaling goes down the tubes.

PMID- 12514737
TI  - Activation of the transcription factor NF-kappaB in Schwann cells is required for
      peripheral myelin formation.
AB  - Peripheral myelin formation is initiated by axonal cues that trigger a
      differentiation program in associated Schwann cells. Here, we define one
      essential differentiation signal: activation of the transcription factor NF
      kappaB. In rat sciatic nerves, NF-kappaB was highly upregulated in pre
      myelinating Schwann cells, and then its expression progressively declined until
      it was nearly absent in adults. Similarly, in co-cultures of Schwann cells and
      sensory neurons, NF-kappaB activation paralleled myelination, and blocking its
      activity or using cells from mice lacking the NF-kappaB subunit p65 markedly
      attenuated myelination. Inhibiting NF-kappaB also prevented activation of Oct-6,
      a transcription factor induced by axonal contact and required for proper myelin
      formation. These results show that the activation of NF-kappaB is an essential
      signal for the progression of axon-associated Schwann cells into a myelinating
      phenotype.

PMID- 12514738
TI  - Associative knowledge controls deployment of visual selective attention.
AB  - According to some models of visual selective attention, objects in a scene
      activate corresponding neural representations, which compete for perceptual
      awareness and motor behavior. During a visual search for a target object, top
      down control exerted by working memory representations of the target's defining
      properties resolves competition in favor of the target. These models, however,
      ignore the existence of associative links among object representations. Here we
      show that such associations can strongly influence deployment of attention in
      humans. In the context of visual search, objects associated with the target were
      both recalled more often and recognized more accurately than unrelated
      distractors. Notably, both target and associated objects competitively weakened
      recognition of unrelated distractors and slowed responses to a luminance probe.
      Moreover, in a speeded search protocol, associated objects rendered search both
      slower and less accurate. Finally, the first saccades after onset of the stimulus
      array were more often directed toward associated than control items.

PMID- 12514739
TI  - Total biosynthesis of hydrocortisone from a simple carbon source in yeast.
AB  - We report on the production of hydrocortisone, the major adrenal glucocorticoid
      of mammals and an important intermediate of steroidal drug synthesis, from a
      simple carbon source by recombinant Saccharomyces cerevisiae strains. An
      artificial and fully self-sufficient biosynthetic pathway involving 13 engineered
      genes was assembled and expressed in a single yeast strain. Endogenous sterol
      biosynthesis was rerouted to produce compatible sterols to serve as substrates
      for the heterologous part of the pathway. Biosynthesis involves eight mammalian
      proteins (mature forms of CYP11A1, adrenodoxin (ADX), and adrenodoxin reductase
      (ADR); mitochondrial forms of ADX and CYP11B1; 3beta-HSD, CYP17A1, and CYP21A1).
      Optimization involved modulating the two mitochondrial systems and disrupting of
      unwanted side reactions associated with ATF2, GCY1, and YPR1 gene products.
      Hydrocortisone was the major steroid produced. This work demonstrates the
      feasibility of transfering a complex biosynthetic pathway from higher eukaryotes
      into microorganisms.

PMID- 12514740
TI  - Structure of the proline dehydrogenase domain of the multifunctional PutA
      flavoprotein.
AB  - The PutA flavoprotein from Escherichia coli plays multiple roles in proline
      catabolism by functioning as a membrane-associated bi-functional enzyme and a
      transcriptional repressor of proline utilization genes. The human homolog of the
      PutA proline dehydrogenase (PRODH) domain is critical in p53-mediated apoptosis
      and schizophrenia. Here we report the crystal structure of a 669-residue
      truncated form of PutA that shows both PRODH and DNA-binding activities,
      representing the first structure of a PutA protein and a PRODH enzyme from any
      organism. The structure is a domain-swapped dimer with each subunit comprising
      three domains: a helical dimerization arm, a 120-residue domain containing a
      three-helix bundle similar to that in the helix-turn-helix superfamily of DNA
      binding proteins and a beta/alpha-barrel PRODH domain with a bound lactate
      inhibitor. Analysis of the structure provides insight into the mechanism of
      proline oxidation to pyrroline-5-carboxylate, and functional studies of a mutant
      protein suggest that the DNA-binding domain is located within the N-terminal 261
      residues of E. coli PutA.

PMID- 12514741
TI  - Structure of the L1 protuberance in the ribosome.
AB  - The L1 protuberance of the 50S ribosomal subunit is implicated in the
      release/disposal of deacylated tRNA from the E site. The apparent mobility of
      this ribosomal region has thus far prevented an accurate determination of its
      three-dimensional structure within either the 50S subunit or the 70S ribosome.
      Here we report the crystal structure at 2.65 A resolution of ribosomal protein L1
      from Sulfolobus acidocaldarius in complex with a specific 55-nucleotide fragment
      of 23S rRNA from Thermus thermophilus. This structure fills a major gap in
      current models of the 50S ribosomal subunit. The conformations of L1 and of the
      rRNA fragment differ dramatically from those within the crystallographic model of
      the T. thermophilus 70S ribosome. Incorporation of the L1-rRNA complex into the
      structural models of the T. thermophilus 70S ribosome and the Deinococcus
      radiodurans 50S subunit gives a reliable representation of most of the L1
      protuberance within the ribosome.

PMID- 12514742
TI  - Tolerance is dependent on complement C3 fragment iC3b binding to antigen
      presenting cells.
AB  - Systemic tolerance can be induced by the introduction of antigen into an immune
      privileged site. Here we investigated the role of complement in the induction of
      tolerance after intraocular injection. We found that the development of antigen
      specific tolerance is dependent on a complement activation product. The ligation
      of the complement C3 activation product iC3b to complement receptor type 3 (the
      iC3b receptor) on antigen-presenting cells resulted in the sequential production
      of transforming growth factor-beta2 and interleukin-10, which is essential for
      the induction of tolerance. These observations may extend to the development of
      both neonatal tolerance and other forms of acquired tolerance.

PMID- 12514743
TI  - The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic
      induction of CYP3A4.
AB  - The drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is thought to be
      involved in the metabolism of nearly 50% of all the drugs currently prescribed.
      Alteration in the activity or expression of this enzyme seems to be a key
      predictor of drug responsiveness and toxicity. Currently available studies
      indicate that the ligand-activated nuclear receptors pregnane X receptor (PXR;
      NR1I2) and constitutive androstane receptor (CAR; NR1I3) regulate CYP3A4
      expression. However, in cell-based reporter assays, CYP3A4 promoter activity was
      most pronounced in liver-derived cells and minimal or modest in non-hepatic
      cells, indicating that a liver-specific factor is required for physiological
      transcriptional response. Here we show that the orphan nuclear receptor
      hepatocyte nuclear factor-4alpha (HNF4alpha; HNF4A) is critically involved in the
      PXR- and CAR-mediated transcriptional activation of CYP3A4. We identified a
      specific cis-acting element in the CYP3A4 gene enhancer that confers HNF4alpha
      binding and thereby permits PXR- and CAR-mediated gene activation. Fetal mice
      with conditional deletion of Hnf4alpha had reduced or absent expression of CYP3A.
      Furthermore, adult mice with conditional hepatic deletion of Hnf4alpha had
      reduced basal and inducible expression of CYP3A. These data identify HNF4alpha as
      an important regulator of coordinate nuclear-receptor-mediated response to
      xenobiotics.

PMID- 12514744
TI  - Genetics analysis of mouse mutations Abnormal feet and tail and rough coat, which
      cause developmental abnormalities and alopecia.
AB  - Mutations in the mouse Brachyury (T) gene are characterized by a dominant
      reduction of tail length and recessive lethality. Two quantitative trait loci,
      Brachyury-modifier 1 and 2 (Brm1 and Brm2) are defined by alleles that enhance
      the short-tail Brachyury phenotype. Here we report on a genetic analysis of a
      visible dominant mutation Abnormal feet and tail (Aft) located in the vicinity of
      Brm1. Affected animals display kinky tails and syndactyly in the hindlimbs, both
      likely resulting from a defect in apoptosis. We observed an unusual genetic
      incompatibility between Aft and certain genetic backgrounds. We show that Aft and
      T are likely to interact genetically, since some double heterozygotes are
      tailless. In addition to the tail and hindlimb phenotypes, Aft-bearing mutants
      display characteristic late-onset skin lesions. We therefore tested for allelism
      between Aft and a closely linked recessive mutation rough coat (rc) and found
      that these two mutations are likely nonallelic. Our results provide a valuable
      resource for the study of mammalian skin development and contribute to the
      genetic analysis of Brachyury function.

PMID- 12514745
TI  - Rapid localization of transgenes in mouse chromosomes with a combined Spectral
      Karyotyping/FISH technique.
AB  - We explored the feasibility of combined Spectral Karyotyping (SKY) and
      Fluorescence In Situ Hybridization (FISH) as means to rapidly map a chromosomally
      integrated renin/green fluorescent protein (GFP) fusion gene construct (Ren-GFP)
      in the transgenic mouse, Tg(Ren-GFP)1Kwg. A sequential hybridization with SKY
      probes followed by FISH gave consistently satisfactory results, demonstrating
      that multiple copies of the Ren-GFP transgene in this transgenic mouse line are
      integrated into a single chromosomal site of Chromosome (Chr) 4, most probably in
      the juxta-centromeric euchromatic region consisting of the A2-A3 domain. Chr 4 as
      a sole carrier of the transgene also was confirmed by co-hybridization to p1 BAC
      clone DNA containing telomeric sequences specific for mouse Chr 4 and the Ren-GFP
      construct in pGEM4Z vector. The hemizygosity of the Ren-GFP transgene is
      maintained not only in bone marrow cells, but also in lung cells proliferating in
      vitro, indicating that stable integration of the Ren-GFP transgene into
      chromosomal DNA was established at a very early embryonic stage. We conclude that
      the SKY/FISH technique is a reliable and facile method for establishing the
      integration site of a transgene. As such, this protocol has obvious advantages
      over traditional backcross methods in terms of time, cost and labor for
      determining the chromosomal location of transgenes.

PMID- 12514746
TI  - DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically
      expressed.
AB  - Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell
      syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified
      within this region to date. GRB10 demonstrates an intricate tissue- and isoform
      specific imprinting profile in humans, with paternal expression in fetal brain
      and maternal expression of one isoform in skeletal muscle. The mouse homolog is
      maternally transcribed. The GRB10 protein is a potent growth inhibitor and
      represents a candidate for SRS, which is characterized by pre- and postnatal
      growth retardation and a spectrum of additional dysmorphic features. Since
      imprinted genes tend to be grouped in clusters, we investigated the imprinting
      status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which
      flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were
      found to replicate asynchronously, suggestive of imprinting, SNP expression
      analyses showed that neither gene was imprinted in multiple human fetal tissues.
      The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region
      on proximal Chr 11, were also biallelically expressed in mice with uniparental
      maternal or paternal inheritance of this region. With the intent of using mouse
      Grb10 as an imprinted control, biallelic expression was consistently observed in
      fetal, postnatal, and adult brain of these mice, in contrast to the maternal
      specific transcription previously demonstrated in brain in inter-specific F1
      progeny. This may be a further example of over-expression of maternally derived
      transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted
      gene identified within 7p11.2-p13.

PMID- 12514747
TI  - Hereditary keratoconus-like keratopathy in Japanese wild mice mapped to mouse
      Chromosome 13.
AB  - Human keratoconus is a common corneal disease with non-inflammatory corneal
      ectasia, and a subset of this disease is heritable. In an effort to establish
      animal models for this disease, we discovered Japanese keratoconus (JKC) mice
      among Mishima molosinus (MSM) mice, an inbred strain of Japanese wild mice (Mus
      musculus molossinus). Typical phenotypic corneas of JKC mice are, like human
      keratoconus, conical in shape, although the corneas were often associated with a
      red punctum at the tip. In contrast to human keratoconus, histological
      examination revealed the inflammatory changes such as infiltration of capillaries
      and hematocytes in JKC mouse corneas. Although JKC mouse corneal change is
      probably secondary to keratitis and is a mouse-specific keratopathy, its
      pathogenesis may be relevant to that of human keratoconus. Linkage analysis
      mapped the responsible gene at the markers D13Mit21, D13Mit252, D13Mit279, and
      D13Mit39, which are located between 21.9 and 34.0 cm of the mouse Chr 13.
      Candidate genes in this region include genes for cathepsins, interleukin, and
      chemotaxin. Further study of JKC mice may shed light on pathogenesis of human
      keratoconus.

PMID- 12514748
TI  - Genomic characterization of the human prion protein (PrP) gene locus.
AB  - Prion protein (PrP) is intimately linked with a class of neurodegenerative
      diseases known as transmissible spongiform encephalopathies (TSEs). Employing
      bioinformatics and direct molecular analysis, we demonstrated that the human PrP
      gene (PRNP) locus, which is situated at Chromosome (Chr) position 20p12-ter,
      contains three genes within a 55-kb interval: PRNP; DOPPEL or PRND, located 20 kb
      3' of PRNP; and a novel gene, designated PRNT, that maps 3 kb 3' to PRND and is
      transcribed to generate at least three alternatively spliced mRNAs. All three
      genes of this locus demonstrate low sequence homology, implying that, although
      they may be evolutionarily related, they are functionally distinct. Analysis of
      both adult and fetal human tissues confirmed the ubiquitous but variable
      expression profile of PRNP, with the highest levels observed in the CNS and
      testis. Contrastingly, although PRND shows a wide tissue expression pattern in
      fetal tissues, it is expressed exclusively in adult testis, whereas all three
      PRNT isoforms were detected only in adult testis, implying that PRND is
      developmentally regulated. An investigation of the regulatory mechanisms
      underlying this complex gene expression pattern from the PRNP locus should
      provide insight into the function of these genes and the possible involvement of
      the non-PrP proteins in the development of TSEs.

PMID- 12514750
TI  - [One stop shopping in pulmonary embolism?].

PMID- 12514749
TI  - Association of bovine neonatal Fc receptor alpha-chain gene (FCGRT) haplotypes
      with serum IgG concentration in newborn calves.
AB  - This report describes allelic variation in FCGRT (which encodes the alpha-chain
      of FcRn) and its association with variation of IgG concentration in neonatal
      calves. Five SNPs were identified by sequencing 1305 bp of FCGRT genomic DNA from
      a multi-breed panel of 96 cattle and 27 founders of a reference population. These
      SNPs defined five FCGRT haplotypes that were verified by segregation and used to
      test association of FCGRT with neonatal IgG concentration in a case-control
      study. This study established that dams with FCGRT haplotype 3 had a
      significantly greater risk of failure of passive transfer in their calves (odds
      ratio [OR] = 3.80, CI95% 1.10-13.18, p = 0.035). Calves with FCGRT haplotype 2
      were less likely to have high levels of passively acquired immunoglobulin (OR =
      0.18, CI95% 0.05-0.68, p = 0.011). These results indicate that the bovine FCGRT
      haplotype markers are in linkage disequilibrium with genetic risk factors
      affecting passive transfer of IgG in beef cattle, an important determinant of
      neonatal calf morbidity and mortality.

PMID- 12514751
TI  - [Renal angiomyolipoma].

PMID- 12514752
TI  - Chest sonography in the diagnosis of pulmonary embolism: a comparison with MRI
      angiography and ventilation perfusion scintigraphy.
AB  - AIM: To compare the diagnostic performance of chest sonography, MRI angiography
      and ventilation/perfusion intigraphy in pulmonary embolism (PE). METHOD: In a
      prospective clinical study, 55 patients (41 women, 14 men, age 23 - 91 years)
      with clinical signs of PE were investigated within 48 hours of the onset of
      symptoms. The final diagnosis was made by MRI angiography (reference method).
      RESULTS: PE was diagnosed in a total of 36 patients. Chest sonography revealed
      rounded or wedge-shaped hypoechoic lesions in 30 patients. On
      ventilation/perfusion (V/P) scintigraphy, 41 patients had positive V/P scans, but
      only 23 were of high probability. Chest ultrasound had a positive predictive
      value of 97 % to diagnose PE. The sensitivity, specificity, the negative
      predictive value and accuracy were 81 %, 84 %, 84 % and 82 %, respectively. As 18
      patients had inconclusive scans, the diagnostic performance of
      ventilation/perfusion scintigraphy was poor. The positive predictive value,
      sensitivity and specificity were 58 %, 42 % and 91 %, respectively. Patients in
      whom PE was excluded mainly suffered from congestive heart failure,
      bronchopulmonary infections or pulmonary hypertension. CONCLUSION: A negative
      sonographic study cannot rule out PE with certainty. However, a chest sonography
      is of acceptable diagnostic value in patients with suspected PE and may be used
      as an adjunct or guide to more established methods.

PMID- 12514753
TI  - [Value of transcranial Doppler sonography during tilt table test in children].
AB  - AIM: Transcranial Doppler sonography was used to asses time relation and
      characteristically changes in middle cerebral artery blood flow velocity before
      syncope during tilt table test in children. METHOD: We performed tilt table tests
      in 40 pediatric patients with a medical history for syncope after exclusion of
      neurologic and cardiologic diseases. Examination was done in a 70 degrees
      postural position under control of electrocardiogram, blood pressure measurement
      and measurements of blood flow velocity of middle cerebral artery by transcranial
      Doppler with 3-MHz probe. RESULTS: In 13 children syncope occurred after 5 to 45
      min (average 23.3). 10 of them were neurocardiogenic syncopes. With it diastolic
      and medium blood flow velocity of middle cerebral artery initial ever increased
      while resistance and pulsatility index decreased. Just before syncope the
      diastolic blood flow velocity decreased dramatically thus no diastolic blood flow
      could be measured, respectively. Almost we could measure no diastolic blood flow
      just before syncope occurred. CONCLUSION: Patients with neurocardiogenic syncope
      do have characteristically blood flow velocity changes of middle cerebral artery
      just before loosing consciousness. Transcranial Doppler is a usefully examination
      during tilt table. Clear transcranial Doppler results can help to prevent
      children from the impending syncope.

PMID- 12514754
TI  - [Criteria of dignity in ultrasound mammography using a 10-MHz-transducer, also
      with regard to tumor size].
AB  - AIM: Ongoing technical progress has increased the accuracy of imaging in
      ultrasound mammography. Using a 10-MHz-transducer, eight different criteria of
      dignity were evaluated for validity, also with regard to the size of a tumor.
      MATERIALS AND METHODS: Over a period of three years, 446 breast tumors were
      ultrasonographically examined by two experienced medical doctors. The study
      comprised only suspicious lesions detected by mammography and/or manual
      palpation. Diagnostic validity was quantified by means of sensitivity,
      specificity, positive and negative predictive value, as well as the ODDS-ratio.
      RESULTS: Ultrasound mammography demonstrated a sensitivity of 94.0 %, specificity
      of 91.4 %, positive predictive value of 95.9 %, and a negative predictive value
      of 99.1 %. Eight different sonographic criteria were validated separately. The
      most important signs of malignancy were (in descending order): a highly echogenic
      halo, spikes, jagged contour, posterior acoustic shadowing, and discontinuity of
      tissue structure. Features of benign disease were: smooth edge, posterior
      acoustic enhancement, displacement margin, bilateral acoustic shadowing and
      continuity of tissue structure. Furthermore, it appeared that the size of a tumor
      only had consequences on posterior shadowing (p = 0.017). All other features did
      not show significant variation in relation to tumor size. CONCLUSION: We were
      able to prove that ultrasound mammography is an excellent medium for the
      differentiation of benign and malignant breast lesions, when precise indication
      criteria were adhered to, even in cases of small tumor size.

PMID- 12514755
TI  - [Real time 3D sonography of the normal fetal heart--clinical evaluation].
AB  - AIM: Aim of the study was to determine the clinical feasibility of real time 3D
      ultrasound in the examination of the normal fetal heart compared to conventional
      2D fetal echocardiography. METHOD: Twenty fetuses with normal hearts at 20 to 38
      weeks of gestation underwent real time 3D ultrasound. Examination data were
      stored on an external notebook. Later analysis and interpretation was done by a
      different sonographer using a special software. RESULTS: In the assessment of the
      four chamber view and the out flow tracts real time 3D ultrasound was equivalent
      to conventional ultrasound. Advantages of realtime 3D ultrasound were the
      possibility of later time-independent off-line analysis and post-processing of
      volume data and generation of new views not available in 2D imaging.
      Disadvantages included low frame rate (16 frames/s), low lateral resolution and
      the lack of Doppler and colour information. CONCLUSION: Simultaneous display of 3
      different views of the fetal heart as well as the construction of spatial
      perspectives ("new views") provide additional useful information to conventional
      fetal echocardiography. Later off-line analysis of 3D volume data can be used for
      sequential analysis of the normal fetal heart with good diagnostic results.
      Currently it remains unclear whether this new method may provide additional
      important information in the assessment of fetal congenital heart defects.

PMID- 12514756
TI  - [Detection of extra-articular soft-tissue involvement in rheumatoid arthritis:
      value of color-coded Doppler sonography].

PMID- 12514757
TI  - [Contrast enhanced ultrasound in the liver using low mechanical index--what is
      the difference?].
AB  - Echo-enhancing agents (EEA), also known as ultrasound contrast media, have
      improved the diagnostic potential of gastroenterologic ultrasound within the last
      years. Initially used to increase color-Doppler signals the potential to use
      harmonic waves being generated by the use of EEAs was established later. The
      effect was based upon the distraction of the EEA bubbles and the resulting pseudo
      Doppler signal, the exam was carried out with high ultrasound energy and
      intermittent switching on and off of the ultrasound beam. Using this effect in
      real-time during continuous scanning is possible since the introduction of new
      EEAs with a flexible shell. This flexible shell oscillates during the scan
      process emitting harmonic signals. This new technology opens new possibilities
      for the detection of liver tumors including the possible characterisation. The
      detection rate for liver metastases can be increased by app. 40 % with this new
      technology. Correct sonographic characterisation of liver tumors can be achieved
      in nearly 100 % more cases.

PMID- 12514758
TI  - [Ultrasonic diagnosis of calciphylactic lesions].
AB  - Calciphylaxis is a serious disease most commonly occurring in patients with end
      stage renal disease characterized by systemic medial calcification of the
      arteries and tissue necrosis due to ischaemia. Secondary infections contribute to
      the high mortality of this disease. Diagnosis is suggested by characteristic skin
      lesions, calcifying septal panniculitis on deep skin biopsy and detection of
      calcifications in conventional radiology. We are able to demonstrate the early
      diagnosis with high resolution high frequency ultrasound prior to the occurrence
      of typical skin lesions facilitating early treatment.

PMID- 12514759
TI  - [Pitfalls in diagnosis of non-Hodgkin-lymphoma of the pancreas].
AB  - A 74 year-old woman was admitted because of upper abdominal pain radiating to the
      back. The patient was in good health prior to onset of symptoms. Both ultrasound
      and endoscopic ultrasound revealed a lesion of low echogenicity in the pancreatic
      head without indication of hepatic lesions, enlarged lymph nodes or vascular
      infiltration. An computed tomography (CT) did not show the lesion in the
      pancreas. Explorative laparotomy was performed. The biopsy specimen revealed a
      diffuse large cell Non-Hodgkin-Lymphoma. This case report illustrates, how simple
      ultrasound studies can detect lesions not seen in more expensive, complex, and
      time consuming imaging techniques like CT. The patient underwent a postoperative
      chemotherapy and is currently well.

PMID- 12514761
TI  - [The continued existence of the term "psychosomatic": the complex relation
      between mind, brain and body].

PMID- 12514762
TI  - [Obesity in childhood and adolescence--first results of a multimodal intervention
      study in Mecklenburg-Vorpommern].
AB  - The prevalence of obesity in children and young adults in Germany has
      dramatically increased during the last decades. We investigated the impact of an
      one year outpatient intervention including physical training, psychotherapy and
      nutrition counselling on psychological status and course of weight of 19
      adolescents who were diagnosed with obesity (intervention group, IG). The
      following questions were of particular interest: Is there a difference between
      children with obesity (n = 19, mean age 12.4 years) and controls (without obesity
      and overweight, control group, CG, n = 38, matched for age and sex) regarding the
      extent of emotional and behavioural problems, self-esteem and physical
      complaints? Does the intervention lead to a decrease of these problems as rated
      by the adolescents and mothers? Can we find a significant reduction of the BMI
      SDS after one year training in the IG? The group comparisons between the IG and
      the CG revealed lower feelings of self-esteem, more self rated physical
      complaints, higher values on measures of depression/anxiety and attention
      problems in the CBCL for children with obesity, compared with controls. After one
      year training adolescents' psychological well being increased significantly while
      the BMI-SDS only decreased moderately. We conclude that children with obesity can
      benefit from receiving outpatient intervention if psychological and medical
      aspects are considered.

PMID- 12514763
TI  - [Differences between female and male patients with eating disorders--results of a
      multicenter study on eating disorders (MZ-Ess)].
AB  - Publications about men with eating disorders are still rare. Therefore, in view
      of the current status of the findings, it seems worthwhile to examine the
      differences that are empirically verified as well as the relevant common features
      between the sexes. Based on a representative sample, therefore, male and female
      patients with eating disorders in inpatient treatment are compared in terms of
      demographic and clinical variables (symptoms and personality), both at the
      beginning of treatment and two-and-a-half years after the inpatient treatment,
      and the findings are discussed with regard to their "gender specificity". The
      study covered 1,171 patients (male and female) with the diagnosis criteria for
      anorexia, bulimia and double diagnosis according to DSM-III-R; 33 of them were
      men. Anorexia cases (342 women and 13 men) and bulimia cases (629 women and 18
      men) were compared at the beginning of treatment with the following instruments:
      Symptom Checklist 90-R; Eating Disorder Inventory; questionnaire for the symptom
      diagnosis of eating disorders; Freiburger Personlichkeitsinventar and Narzissmus
      Inventar. As a measure of success in the 2.5 year catamnesis (764 women and 20
      men), operationalized criteria were defined using the LIFE. The 2.8 % share of
      men with eating disorders in inpatient treatment again confirms the special
      nature of this clinical disorder for men. An interesting result is the later
      onset of illness in male anorexia cases. Coinciding with comparable studies,
      there are only minor differences in eating behavior, but the differences in body
      experience are much more pronounced. In bulimic men, there is a higher percentage
      of homosexuals and they are more satisfied with their body. Anorectic men have a
      greater gain from the illness, are more concerned about their health and are less
      performance-minded than female anorectics. The differences that were found
      clearly indicate that these occur especially in the area of dealing with the body
      and the significance of the body. One of the reasons why the results in the area
      of personality and sexual identity are interesting is that they point to
      differences which definitely appear to be significant, not just between the
      sexes, but also between male anorexia and bulimia.

PMID- 12514764
TI  - [Personal child-related motives and attitudes in females with eating disorders-
      indicators for gender role conflicts?].
AB  - In the context of the etiology of eating disorders it is common to discuss
      emotional conflicts related to the identification with the female gender role.
      Based upon this theoretical background this study was designed to examine the
      attitudes of 46 females suffering from anorexia or bulimia towards their wish to
      have children. It was assumed that the personal evaluation of motherhood and
      attitudes towards own children might reflect one important aspect of the
      identification with the female gender role. The results of this study are based
      on the "Leipziger Fragebogen zu Kinderwunschmotiven" and the "Leipziger
      Fragebogen zu Einstellungen zum Kinderwunsch" by Stobel-Richter and Brahler and
      suggest that females suffering from eating disorders are more likely to refuse
      traditional concepts of the female gender role, especially a traditional concept
      of motherhood.

PMID- 12514765
TI  - [The incidence of pathological eating behaviour among schoolchildren in a large
      urban area].
AB  - Clinical experience and international epidemiological studies indicate an
      increase in pathological eating behaviour as well as a shift towards increasingly
      younger children. In order to study its frequency in Germany a large random
      sample, 2,844 pupils of the 10 th class level were contacted as part of a school
      medical examination to take part in a questionnaire study using the Eating
      Disorder Inventory. Age, gender, BMI and the type of school were also recorded.
      From the statistical description of healthy matching samples, gender-specific cut
      off values were established and this methodical approach was discussed
      critically. Of the predominantly 15/16-year-old schoolchildren, 83 % took part in
      the study. Regardless of gender and type of school, more than 7% had an anorexic
      body weight and 10% of female and 2% of male pupils had bulimic eating behaviour.

PMID- 12514766
TI  - Nitric oxide in liver transplantation: pathobiology and clinical implications.
AB  - The gaseous molecule nitric oxide is involved in a variety of liver transplant
      relevant processes, including ischemia-reperfusion injury, acute cellular
      rejection, and circulatory changes characteristic of advanced liver disease. This
      review article focuses on new advances relating to the role of nitric oxide in
      these syndromes with an emphasis on pathobiology and potential clinical
      implications.

PMID- 12514767
TI  - Longitudinal assessment of mortality risk among candidates for liver
      transplantation.
AB  - Liver allocation policy recently was modified to use the Model for End-Stage
      Liver Disease (MELD) for patients with chronic liver disease to stratify
      potential recipients according to risk for waitlist death. In this study, a
      retrospective cohort of 760 adult patients with chronic liver disease placed on
      the liver transplant waitlist between January 1995 and March 2001 and followed up
      for up to 74 months was studied to assess the ability of the MELD to predict
      mortality among waitlisted candidates and evaluate the prognostic importance of
      changes in MELD score over time. Serial MELD scores predicted waitlist mortality
      significantly better than baseline MELD scores or medical urgency status. Each
      unit of the 40-point MELD score was associated with a 22% increased risk for
      waitlist death (P <.001), whereas medical urgency status was not a significant
      independent predictor. For any given MELD score, the magnitude and direction of
      change in MELD score during the previous 30 days (DeltaMELD) was a significant
      independent mortality predictor. Patients with MELD score increases greater than
      5 points over 30 days had a threefold greater waitlist mortality risk than those
      for whom MELD scores increased more gradually (P <.0001). We conclude that
      mortality risk on the liver transplant waitlist is predicted more accurately by
      serial MELD score determinations than by medical urgency status or single MELD
      measurements. DeltaMELD score over time reflects progression of liver disease and
      conveys important additional prognostic information that should be considered in
      the further evolution of national liver allocation policy.

PMID- 12514768
TI  - Is the change in MELD score a better indicator of mortality than baseline MELD
      score?

PMID- 12514769
TI  - ABO-incompatible liver transplantation with no immunological graft losses using
      total plasma exchange, splenectomy, and quadruple immunosuppression: evidence for
      accommodation.
AB  - ABO-incompatible liver transplants (LTX) have been associated with a high risk of
      antibody-mediated rejection, poor patient and graft survival, and a high risk of
      vascular thrombosis and ischemic bile duct complications. We used
      pretransplantation and posttransplantation double-volume total plasma exchange
      (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or
      mycophenolate mofetil, prednisone, cyclosporine or tacrolimus, and OKT3
      induction) in 14 patients receiving ABO-incompatible LTX between June 1992 and
      February 2001: A(1) to O (seven), B to O (two), B to A (two), A to B (one), AB to
      A (one), and AB to O (one). Actuarial 1- and 5-year patient and graft survival
      rates are 71.4% and 61.2 % and 71.4% and 61.2%, respectively, with a mean follow
      up of 62.9 +/- 39.4 months. Ten acute cellular rejections occurred, and the mean
      time to the first episode was 62 +/- 33 days. All were steroid sensitive. No
      antibody-mediated rejection or vascular thromboses occurred. Pretransplantation
      pre-TPE immunoglobulin (Ig) G mean isohemagglutinin titers were 262 +/- 326,
      compared with pretransplantation post-TPE titers of 65 +/- 103 (P =.04). Eight of
      nine patients with measurable titers before and after TPE achieved a reduction in
      titers. The mean number of posttransplantation TPE was 5.5 +/- 4.1 (range, 0 to
      12), and the last TPE was on postoperative day 9.4 +/- 5.3. IgG isohemagglutinin
      titers 2 weeks posttransplantation had increased to 153 +/- 309 (P =.03 compared
      with pretransplantation pre-TPE IgG). ABO-incompatible liver transplantations can
      be performed with acceptable patient and graft survival rates with a low risk of
      antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple
      immunosuppression. Recovery of isohemagglutinin antibody levels without humoral
      rejection suggests that accommodation may be the protective mechanism preventing
      late antibody-mediated rejection.

PMID- 12514770
TI  - ABO-incompatible liver transplant: is it justifiable?

PMID- 12514771
TI  - Systemic and regional changes in plasma endothelin following transient increase
      in portal pressure.
AB  - An acute increase in portal pressure or reduction in portal inflow has been shown
      to decrease renal plasma flow (RPF). The aim of the study was to evaluate
      regional and systemic hemodynamics after acute occlusion of a transjugular
      intrahepatic portosystemic stent-shunt (TIPSS) and study the effect of the same
      on plasma endothelin (ET-1) levels in the systemic circulation, renal vein, and
      hepatic vein. Sixteen patients attending for portography after previous TIPSS
      placement were studied. The shunt was acutely occluded with an angioplasty
      balloon for 12 minutes. Changes in portal pressure gradient (PPG), hepatic plasma
      flow (HPF), RPF, cardiac output (CO), and systemic vascular resistance (SVR) were
      measured before and after shunt occlusion. Blood was collected from the femoral
      artery and hepatic and renal veins for ET-1 measurement. At T = 0, SVR correlated
      with circulating arterial ET-1 level (r = 0.74; P <.05). After shunt occlusion (T
      = 12 minutes), heart rate, CO, and mean arterial pressure decreased (P <.05),
      whereas PPG increased (P <.05). RPF decreased from 485 +/- 55 to 282 +/- 47
      mL/min (P <.01), whereas HPF increased from 700 +/- 39 to 779 +/- 33 mL/min (P
      <.001). There was a significant increase in arterial concentration and renal
      production, and decrease in hepatic production of ET-1. Veno-arterial (V-A)
      concentration difference in ET-1 level in the renal vein, as well as renal flux
      of ET-1, increased significantly, whereas hepatic vein V-A concentration
      difference and hepatic flux of ET-1 decreased significantly. At T = 12 minutes,
      ET-1 renal output correlated negatively with RPF (r = 0.72; P <.05). Results of
      this study show that an acute increase in portal pressure and reduction in portal
      inflow brought about by occlusion of a TIPSS shunt decreases RPF and increases
      HPF. These hemodynamic changes are accompanied by increases in arterial, renal
      vein, and hepatic vein ET-1 concentrations, which may possibly mediate the
      observed findings.

PMID- 12514772
TI  - Presence of methylated arginine derivatives in orthotopic human liver
      transplantation: relevance for liver function.
AB  - Orthotopic liver transplantation (OLT) is a frequent option in the treatment of
      liver diseases. During the cold ischemia period of the donor liver, there is an
      accumulation of metabolites that are potent inhibitors of the cytokine-inducible
      and endothelial nitric oxide synthase isoenzymes. We identified the presence of L
      N-monomethylarginine and asymmetric dimethylarginine (ADMA) as the main
      inhibitors by means of analytic high-pressure liquid chromatography and mass
      spectrometry techniques. An average ADMA concentration of 450 micromol/L was
      measured in the preservation medium of donor livers with poor outcomes after OLT.
      A statistically significant relationship was observed between the concentration
      of methylated arginine derivatives in the graft and liver function after OLT.
      These data suggest that measurement of methylated arginine, released after liver
      protein catabolism, might provide an indication of functional status of the liver
      that can help the development of strategies intended to improve graft viability.

PMID- 12514773
TI  - A United States compassionate use study of lamivudine treatment in
      nontransplantation candidates with decompensated hepatitis B virus-related
      cirrhosis.
AB  - Patients with hepatitis B-related decompensated cirrhosis have limited treatment
      options. This prospective, multicenter study assessed lamivudine in 75 patients
      with decompensated cirrhosis, the majority of whom (93%) were not candidates for
      liver transplantation. At baseline, all 75 patients tested positive for hepatitis
      B surface antigen [HBsAg (+)] and 62% tested positive for hepatitis B e antigen
      [HBeAg (+)]. Hepatitis B virus (HBV) DNA levels were detectable in 64% of
      patients by the branched chain DNA (bDNA) assay. Patients received lamivudine 100
      mg once daily (median duration, 12.7 months; range, 0.5 to 33 months). In
      patients with detectable HBV DNA pretreatment, the virus became undetectable by
      the bDNA assay in 69% of patients with > or = 6 months treatment and in 64%
      overall. Alanine aminotransferase (ALT) level improved in 90% and normalized in
      55% of patients with > or = 6 months treatment and in 48% overall. Improvements
      in bilirubin and albumin levels occurred throughout treatment. The median Child
      Pugh score improved from a baseline of 10 to 8 at last visit, with 31% (23/75)
      having an improved score of > or = 2 points, 57% (43/75) unchanged (< 2 points),
      and 12% (9/75) worsened (> or = 2 points). A virologic breakthrough developed in
      eight of 41 patients (18%) after a median of 13.1 months of treatment. Tyrosine
      methionine-aspartate-aspartate (YMDD) variant HBV was detected in three of four
      patients tested. Nevertheless, at last visit, ALT, albumin, and bilirubin levels
      were similar for patients with and without breakthrough. Lamivudine treatment can
      lead to significant improvements in liver disease severity in nontransplantation
      candidates with advanced disease. Additional studies of lamivudine in combination
      with other antivirals are indicated for the large population of patients
      worldwide with advanced HBV-related cirrhosis and inadequate access to liver
      transplantation.

PMID- 12514774
TI  - Lack of antiviral effect of a short course of mycophenolate mofetil in patients
      with chronic hepatitis C virus infection.
AB  - Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in
      the management of liver transplant recipients. MMF inhibits the inosine
      monophosphate dehydrogenase that has been shown to have in vitro antiviral
      properties against flaviviruses, suggesting the possibility that it might also
      inhibit the hepatitis C virus (HCV). The goal of this short-term dose escalation
      study was to assess the antiviral effects of MMF on HCV replication. Patients
      with chronic hepatitis C who had not undergone liver transplantation were
      randomized to 8 weeks of treatment with one of four mycophenolate dose regimens
      (1000 mg orally twice daily, 500 mg orally twice daily, 250 mg orally twice
      daily, or a matched oral placebo twice daily). All groups were double-blinded.
      Quantitative HCV RNA levels and serum alanine aminotransferase were assessed at
      baseline, at weeks 2, 4, and 8 of dosing, and at weeks 4 and 8 of follow-up.
      Thirty patients met inclusion criteria, enrolled, and were randomized. HCV RNA
      levels did not change significantly during treatment. Specifically, no subject
      became virus negative or had a one-log decrease in virus level. Serum
      aminotransferase level did not normalize in any subject. The most common side
      effects were headache, nausea, and diarrhea. Mycophenolate alone does not appear
      to have a significant antiviral or biochemical effect in patients with chronic
      hepatitis C.

PMID- 12514775
TI  - Health-related quality of life in pediatric liver transplant recipients: A single
      center study.
AB  - The goals of the present study were (1) to measure health-related quality of life
      (HRQOL) in pediatric liver transplantation (LT), (2) to identify demographic and
      clinical factors that correlate with HRQOL, and (3) to compare two instruments
      that have been used to measure HRQOL in children and adolescents. We conducted a
      single-center cross-sectional study of 77 pediatric LT recipients ages 5 to 18
      years, all of whom had had LT at least 6 months previously. We used the Child
      Health Questionnaire Parent Form 50 (CHQPF50) and the PedsQL4.0 to determine
      measured dimensions of physical and psychosocial health from the parents'
      perspective. Individual scale scores range from 0 to 100, with higher scores
      reflecting better health. Data on demographics, clinical status at
      transplantation, posttransplantation clinical course, and graft function were
      collected to identify predictors of posttransplantation HRQOL. Fifty-three
      percent of the liver transplant recipients had biliary atresia, 78% were white,
      and 61% were female. The mean age at LT was 3.8 +/- 3.6 years, and the range of
      time since LT was 1 to 15 years. HRQOL in pediatric liver transplant recipients
      was lower than that reported for healthy children but similar to that for
      children with other chronic illness. Age at transplantation, the time elapsed
      since transplantation, hospitalizations within the previous year, maternal
      education, and race were significant predictors of physical health. Age at
      transplantation and maternal education predicted psychosocial function. HRQOL was
      decreased in a population of pediatric liver transplant recipients compared with
      the general population and similar to that for children with chronic illness.
      Prospective longitudinal studies will permit us to define predictors of HRQOL at
      different periods of time after transplantation. The information gained from this
      study will help us to better define expectations and the clinical course after
      liver transplantation to patients and their families.

PMID- 12514776
TI  - The effect of donor body mass index on primary graft nonfunction,
      retransplantation rate, and early graft and patient survival after liver
      transplantation.
AB  - Previous studies have suggested that moderate donor liver steatosis is associated
      with an increased incidence of primary graft nonfunction (PGNF), delayed graft
      function, early graft loss, and retransplantation rates. The objective of our
      study was to determine the effect of donor body mass index (dBMI), after
      adjusting for other known confounding variables, on PGNF, early graft failure,
      retransplantation rate, and patient survival. The United Network for Organ
      Sharing (UNOS) database (1987 to 2001) of 22,303 adult patients, excluding
      patients of pediatric age (age less than 18 years) and those with multiple organ
      transplantations, living donors, and retransplantations, was used for this study.
      Based on the BMI (kg/m(2)) of the organ donor, transplant recipients were divided
      into four groups as follows: BMI < 25 (group 1, n = 11,660), 25 to 29.9 (group 2,
      n = 7418), 30 to 34.9 (group 3, n = 2301), and > or = 35 (group 4, n = 924).
      Information on donor liver histology was available for 1603 patients who
      underwent transplantation after 1999, and this subgroup was divided into three
      groups based on severity of steatosis (group A, < 20%; group B, 20% to 35%; group
      C, > 35%). Incidence of PGNF and early retransplantation rates were similar in
      groups 1 to 4 and in groups A, B, and C. Logistic regression analysis showed that
      dBMI or severity of steatosis was not a predictor of PGNF and early
      retransplantation. Cox regression analysis, after adjusting for confounding
      variables, showed similar patient and graft survival at 1 month and 1, 2, and 5
      years for groups 1 to 4, and at 1 month and 6 months for groups A, B, and C.
      Severe donor obesity or moderate steatosis did not influence short-term and long
      term outcome of liver transplantation.

PMID- 12514777
TI  - Prostaglandin E1 improved the function of transplanted fatty liver in a rat
      reduced-size-liver transplantation model under conditions of permissible cold
      preservation.
AB  - The aim of this study was to determine whether the minimum necessary volume of a
      moderate fatty liver graft was similar to the normal liver volume and to
      elucidate means for improving the function of the transplanted fatty liver if it
      were inferior in volume to a normal liver under conditions of permissible cold
      preservation. Nine-week-old male Wistar rats were used. Normal rat chow was fed
      to the normal liver group, and fat-enriched rat chow was fed to the fatty liver
      group for 4 weeks to induce a moderately fatty liver. Liver transplantation with
      various volumes of reduced-size grafts, including whole liver graft (100%LT), 70%
      volume graft (70%LT), and 30% volume graft (30%LT), was performed with both
      groups of rats as donors. All procedures were performed under the conditions of 2
      hour cold preservation. All rats with an implanted normal liver were surviving at
      7 days after the operation regardless of the graft volume (100%LT, 5 of 5; 70%LT,
      5 of 5; 30%LT, 5/5). In contrast, the survival rates decreased according to the
      graft volume in rats implanted with fatty livers (100%LT, 8 of 8; 70%LT, 5 of 8;
      30%LT, 2/8). To improve the survival of 30%LT with fatty liver, we employed two
      potent inhibitors of ischemia-reperfusion injury: FK506 and prostaglandin E1.
      Though FK506 had no advantageous effect, prostaglandin E1 significantly improved
      the survival rate and diminished serum levels of alanine aminotransferase and
      hyaluronic acid. In conclusion, the volume of graft necessary for successful
      transplantation is larger in fatty livers than in normal livers in permissible
      cold preservation. Also, prostaglandin E1 protects grafts against ischemia
      reperfusion injury and improves the functioning of a transplanted fatty liver.

PMID- 12514778
TI  - Liver transplantation for primary biliary cirrhosis: a long-term pathologic
      study.
AB  - Although recurrent primary biliary cirrhosis (PBC) after liver transplantation
      (LT) has been reported, the full spectrum of changes and progression to fibrosis
      and cirrhosis is not yet established. We performed a detailed retrospective
      clinicopathologic analysis of 43 patients who underwent LT for PBC. Eight
      patients (18.6%) had definite recurrent PBC with florid duct lesions, 5 patients
      (11.6%) had recurrence with features of autoimmune liver disease, not otherwise
      specified (AILD-NOS), 7 patients (16.3%) had plasmacytosis only, 4 patients
      (9.3%) had chronic rejection, 18 patients (41.9%) have no recurrence at present,
      and 1 patient (2.3%) had acquired hepatitis C. Although definite diagnoses of PBC
      and AILD-NOS recurrences (n = 13) were made 1 month to 14 years (median, 4 years)
      post-LT, all patients had plasmacytosis in their earlier biopsy specimens. Also,
      these patients showed similar pre-LT and post-LT clinical features, with
      progressive fibrosis in 4 of 8 and 2 of 5 patients, respectively. Four of 13
      patients with definite recurrence and 14 of 18 patients with no recurrence were
      administered azathioprine (AZA) as part of their post-LT therapy (P =.01). Six of
      13 and 16 of 18 patients currently are alive, with median follow-ups of 11 and 5
      years, respectively. No significant differences were seen with donor-recipient
      group A, group B, group O blood type, sex, or HLA mismatches; native liver
      histological characteristics; or tacrolimus-based therapy. In conclusion,
      recurrent autoimmune liver disease was seen in 30% of patients after LT for PBC
      and had features of PBC and/or AILD-NOS. Progression seen in 46% of patients was
      associated with late graft failure. Patients with no recurrent disease had
      shorter follow-up periods and more frequent immunosuppression, including AZA;
      some may still develop recurrence with longer follow-up.

PMID- 12514779
TI  - Mediastinal recurrence of alveolar echinococcosis after liver transplantation.

PMID- 12514780
TI  - Can early liver biopsies predict long-term outcome of the graft?
AB  - BACKGROUND: Chronic rejection (CR) in liver allografts show a rapid onset and
      progressive course, leading to graft failure within the first year after
      transplantation. Most cases are preceded by episodes of acute cellular rejection
      (AR), but histological features predictive for the transition toward CR are not
      well documented. METHOD: We assessed the predictive value of centrilobular
      necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular
      inflammation in the development of CR. One-week and one-month biopsy specimens of
      12 patients with CR were compared with those of a control group consisting of 17
      patients, who experienced AR without developing CR. The progress of the
      histological changes was further evaluated in follow-up biopsy specimens of the
      CR group taken at 2 months and beyond 3 months after transplantation. RESULT:
      Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were
      common features in both groups at 1 week. At 1 month, the incidence declined in
      the control group. The CR group showed an increased incidence and persistence of
      these features in the follow-up specimens. The incidence and median grade of
      severity of CVE was significantly higher in the CR group (p=0.04, and P<0.001).
      The severity of portal and lobular inflammation was also more pronounced in the
      CR group (P+0.01 and 0.069). Conversely, in the control group the incidence of
      the lobular features decreased and the severity of CVE declined significantly
      (P=0.03). CONCLUSION: The shift from a predominantly portal-based process toward
      lobular graft damage represents the early transition of AR to CR, for which a
      modification of immunosuppression might be necessary to prevent graft loss.

PMID- 12514781
TI  - Sarcoidosis: a mysterious tale of inflammation, tissue remodeling, and matrix
      metalloproteinases.

PMID- 12514782
TI  - Matrix metalloproteinases and their tissue inhibitors in the lesions of cardiac
      and pulmonary sarcoidosis: an immunohistochemical study.
AB  - The pathogenesis of the tissue damage and fibrosis in sarcoidosis is poorly
      understood. The matrix metalloproteinases (MMPs) and their tissue inhibitors
      (TIMPs) must be considered in this regard, because they control the lysis of
      connective tissue components. Immunohistochemical studies (peroxidase and dual
      labeling for confocal microscopy) of reactivity for MMP-1, MMP-2, MMP-3, MMP-7,
      MMP-9, and the 4 membrane-type-MMPs were made on tissues from patients with
      cardiac (n = 4) and pulmonary (n = 5) sarcoidosis. The granulomas were
      histochemically similar in both organs. The multinucleated giant cells (MGCs)
      showed moderate reactivity for MMP-1 and MMP-9 and variable reactivity for MMP-2
      and MMP-3; in addition, they showed colocalization of MT-1-MMP, which activates
      MMP-2. The reactivity of epithelioid cells (ECs) was moderate for MMP-2 and mild
      for other MMPs. Macrophages showed weaker reactivity for MMPs than did MGCs and
      ECs. All 3 types of cells showed very low reactivity for TIMPs. Staining for type
      IV collagen showed focal damage to the basement membranes of cardiac myocytes and
      pulmonary alveoli near the granulomas. The cells in sarcoid granulomas contain an
      abundance of MMPs and a paucity of TIMPs. The MGCs also contain MT-1-MMP and thus
      can activate MMP-2 in the granulomas. The MMPs can cause damage to adjacent
      cardiac myocytes and pulmonary alveoli, leading to the interstitial fibrosis
      produced by sarcoidosis.

PMID- 12514783
TI  - Iatrogenic cardiac papillary fibroelastoma: a study of 12 cases (1990 to 2000).
AB  - Cardiac papillary fibroelastoma (PFE) is a rare, benign, slow-growing tumor of
      the endocardium. Whether it represents a reactive tumoral lesion or a true
      neoplasm remains a matter of debate. However, an anecdotal association of PFEs
      with previous cardiac surgery has been reported. The current study was undertaken
      to determine the frequency and nature of iatrogenic events associated with PFEs
      and to provide a comprehensive review of the topic. The study group comprised 12
      cases seen between 1990 and 2000, with specimens from 7 women and 5 men. Six
      developed postoperatively and 6 developed after thoracic irradiation. The 9 Mayo
      cases represented 18% of all surgically excised PFEs during the study period. The
      mean age at operation was 54 years (range, 29 to 79 years). The mean interval
      between the iatrogenic event and excision of the tumor was 18 years (range, 9 to
      31 years). In 58% of cases, the presence of multiple tumors was either confirmed
      pathologically (41.7%) or strongly suggested by echocardiography (16.6%). Among
      patients who had undergone previous cardiac surgery, PFEs were found in the
      chamber closest to the procedure. Similarly, in patients who had received
      radiation therapy, tumors developed in the left atrium, in the right ventricle
      and atrium, and on the tricuspid valve within the radiation field. In conclusion,
      iatrogenic PFEs may be relatively common among all such tumors, are frequently
      multiple, and often involve nonvalvular endocardial surfaces.

PMID- 12514784
TI  - Portal lymphocytic infiltrate in alcoholic liver disease.
AB  - The aim of this study was to estimate the frequency of lymphocytic portal
      infiltrate in human alcoholic liver disease and to determine whether it was
      correlated with liver injury. This retrospective study included 200 consecutive
      patients referred between February 1996 and March 2001 to the Service Central
      d'Hepato-Gastroenterologie at Groupe Hospitalier Pitie-Salpetriere Hospital,
      Paris, France. The inclusions criteria were as follows: (1) daily alcohol
      consumption greater than 40 g; (2) appropriate serological exclusion of B and C
      viral hepatitis; and (3) available liver biopsy specimen. Autoimmune hepatitis
      was excluded in all patients with the aid of a consensus scoring system. Forty
      percent of the patients had a predominantly lymphocytic portal infiltrate. On
      stepwise logistic regression of the predictive value of the 5 variables (gender,
      age, daily alcohol consumption, steatosis, and portal and septal fibrosis index),
      only 2 statistically independent predictors of predominant lymphocytic portal
      infiltrate were identified: portal and septal fibrosis index (P <.05) and age (P
      <.05). In conclusion, predominantly portal lymphocytic infiltrate occurs
      frequently in alcoholic liver disease, even in patients without serological
      markers of B and C viral hepatitis. Moreover, after adjustment for age, portal
      and septal fibrosis index remains significantly associated with the presence of a
      predominantly lymphocytic portal infiltrate. These results suggest that
      lymphocytes may play a role in the pathogenesis of alcohol-induced liver
      fibrosis.

PMID- 12514785
TI  - Comparative immunohistochemical profile of hepatocellular carcinoma,
      cholangiocarcinoma, and metastatic adenocarcinoma.
AB  - Distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and
      metastatic adenocarcinoma (MA) involving the liver can be problematic, often
      requiring the use of immunohistochemistry to facilitate diagnosis. Hep Par 1, a
      monoclonal antibody with expression confined primarily to benign and malignant
      hepatocytes, has recently become commercially available. We evaluated Hep Par 1
      along with other immunohistochemical markers used to differentiate HCC, CC, and
      MA, including AE1/AE3, CAM 5.2, B72.3, monoclonal carcinoembryonic antigen
      (mCEA), polyclonal CEA (pCEA), alpha-fetoprotein (AFP), factor XIIIa, inhibin,
      CD10, villin, MOC-31, cytokeratin (CK) 7, CK 19, and CK 20, to determine the
      markers most useful in differentiating these entities. Forty-two cases of HCC, 9
      cases of CC, and 56 cases of MA (24 colon, 15 pancreas, 8 ovary, 5 breast, and 4
      stomach) were studied. Hep Par 1 was sensitive and specific for HCC, with 38 of
      42 (90%) cases staining positively, whereas reactivity was observed in only 8 of
      56 (14%) MAs and 0 of 9 CCs. Though limited somewhat by poor sensitivity, a bile
      canalicular pattern of staining with pCEA, CD10, and villin was specific for HCC
      and was not observed in the other tumors. Lack of mCEA and MOC-31
      immunoreactivity was also characteristic of HCCs. CK 19 positivity favored CC
      over HCC, but was not useful in differentiating CC from MA. Expression of AFP,
      although observed in only about one third of the cases, favored HCC over CC and
      MA. CK 7 and CK 20 were also useful in this differential diagnosis, particularly
      when dealing with MA of colonic origin. AE1/AE3, CAM 5.2, B72.3, inhibin, and
      factor XIIIa were noncontributory in differentiating these entities.

PMID- 12514786
TI  - Analysis of c-kit protein expression in small-cell lung carcinoma and its
      implication for prognosis.
AB  - Recently, therapies targeting signaling pathways involved in the pathogenesis of
      different tumors have been developed. Studies have shown that the tyrosine kinase
      inhibitor STI-571 (Gleevec) is used successfully against tumors expressing the c
      kit oncogene, such as gastrointestinal stromal tumors (GISTs). A recent in vitro
      study also demonstrated an antiproliferative effect of STI-571 on small-cell lung
      cancer (SCLC) cell lines. To determine the expression of c-kit in SCLC, we
      retrospectively analyzed presence of c-kit by immunohistochemistry in biopsy
      samples from patients with SCLCs. Formalin-fixed, paraffin-embedded archival
      tissue samples from 30 SCLCs were stained with an antibody directed against c-kit
      (CD117) by immunohistochemistry. Thirty cases of SCLCs, including 17 males (age
      44 to 89) and 13 females (age 21 to 85), were examined. Sixteen of 30 (53.3%)
      SCLCs showed c-kit expression. Kaplan-Meier survival analysis with a log-rank
      test revealed that patients with c-kit expression had a tendency toward lower
      survival than c-kit-negative patients (median survival, 6 months versus 31
      months, P =.062). Based on previously established anti-c-kit effects of STI-571
      on SCLC cell lines and our findings, clinical trials may be considered for
      selected SCLC patients with c-kit expression. Furthermore, determination of c-kit
      in SCLC may have a prognostic value in SCLC patients.

PMID- 12514787
TI  - Immunohistochemical characterization of p57(KIP2) expression in early
      hydatidiform moles.
AB  - The differentiation of complete mole (CM), an aberrant androgenetic conceptus,
      from partial mole (PM) and hydropic abortion (HA) in early gestations is very
      important for patient management. In this study, 10 diploid voluntary artificial
      abortions (ABs), 20 diploid HAs, 20 triploid PMs, and 44 diploid CMs (including 4
      persistent diseases), all of which were in the first trimester, were evaluated by
      immunohistochemistry of formalin-fixed tissues using a monoclonal antibody
      against p57(KIP2) protein (p57), a putative paternally imprinted inhibitor gene.
      DNA ploidy in all cases was analyzed by flow cytometry. In all ABs, nuclear p57
      was strongly expressed in cytotrophoblasts, intermediate trophoblasts, villous
      stromal cells, and decidual stromal cells but was absent in syncytiotrophoblast.
      In diploid CMs, p57 expression in cytotrophoblasts and villous stromal cells was
      either absent (37 cases) or very low (7 cases). Villous intermediate trophoblasts
      stained for p57 in 12 cases of CM. On the other hand, 16 HAs and 19 PMs showed
      p57 levels comparable to those observed in ABs. Decidual stromal cells provided a
      reliable internal control in all cases. These findings support the hypothesis
      that misexpression of p57 is involved in the abnormal development of androgenetic
      CMs. This immunohistochemical analysis is a useful tool for the differential
      diagnosis of CMs.

PMID- 12514788
TI  - Transforming growth factor-beta1 induces tumor stroma and reduces tumor
      infiltrate in cervical cancer.
AB  - Cervical carcinomas consist of tumor cell nests surrounded by varying amounts of
      intratumoral stroma containing different quantities and types of immune cells.
      Besides controlling (epithelial) cell growth, the multifunctional cytokine
      transforming growth factor-beta(1) (TGF-beta(1)) is involved in the formation of
      stroma and extracellular matrix (ECM) and in immunosuppression. Several
      malignancies are known to be associated with enhanced production of TGF-beta(1),
      repression or mutation of TGF-beta transmembrane receptors, or mutations at the
      postreceptor intracellular signaling pathway. The aim of our study was to
      investigate the role of tumor cell-derived TGF-beta(1) on the amount of
      intratumoral stroma; the deposition of collagen IV, fibronectin, and laminin; and
      the tumor infiltrate in cervical carcinoma. The expression of TGF-beta(1) mRNA in
      108 paraffin-embedded cervical carcinomas was detected by mRNA in situ
      hybridization. Immunohistochemistry was used to investigate the amount of tumor
      stroma and ECM proteins and the extent of the tumor infiltrate. Plasminogen
      activator inhibitor-1 (PAI-1) protein expression in tumor cells was determined to
      verify the biological activity of TGF-beta(1.) Cytoplasmatic TGF-beta(1) mRNA
      expression in tumor cells was significantly correlated with the amount of
      intratumoral stroma and the deposition of collagen IV. TGF-beta(1) mRNA
      expression in every tumor was accompanied by PAI-1 expression, indicating
      biological activity of TGF-beta(1). An inverse relationship between TGF-beta(1)
      mRNA expression in tumor cells and the extent of the tumor infiltrate was
      demonstrated. Our results indicate that cervical cancer cells affect the amount
      and the composition of the intratumoral stroma and the tumor infiltrate by the
      production and secretion of TGF-beta(1).

PMID- 12514789
TI  - CDKN2A promoter methylation in gastric adenocarcinomas: clinical variables.
AB  - The CDKN2A gene encodes a cyclin-dependent kinase inhibitor, p16, which promotes
      cell cycle arrest. Methylation of the promoter region of the gene
      transcriptionally inactivates the gene. We have analyzed the methylation status
      of the promoter region of the CDKN2A gene in gastric adenocarcinomas using
      methylation-specific polymerase chain reaction. We also examined the tumors by
      immunohistochemistry for p16 protein. Of 114 gastric adenocarcinomas analyzed by
      immunohistochemistry, 34 cases (30%) were negative for p16 protein. Twenty-four
      of these 34 cases (71%) had methylation of the promoter region of the CDKN2A
      gene. Methylation of the promoter was strongly associated with loss of p16
      protein by immunohistochemistry (P <0.0001). Neither stage, grade, anatomic site,
      or histologic subtype of the tumor nor age, gender, ethnic origin, or survival
      time of the patient were significantly different between the groups characterized
      by tumors with and without methylation. CDKN2A promoter methylation was not
      significantly associated with microsatellite instability.

PMID- 12514790
TI  - Bizarre parosteal osteochondromatous proliferation (Nora's lesion): a
      retrospective study of 12 cases, 2 arising in long bones.
AB  - Twelve cases of bizarre parosteal osteochondromatous proliferation (BPOP), also
      known as Nora's lesion, are reported. Ten lesions were located in the small bones
      of the hands, and 2 were located in long bones (femur and proximal tibia).
      Patient age ranged from 12 to 63 years (average, 30.3 years). Radiography of the
      lesions in the hand bones showed calcific masses attached to the underlying
      cortex, without interruption of the latter. The long bone lesions revealed
      unusual findings. In the femur, BPOP presented with extensive cortical
      destruction and was suggestive of a malignant lesion. This presentation has not
      been described to date. In the tibia, the lesion was located in the soft tissue
      without cortical attachment. This type of BPOP probably represents an immature
      lesion that over time will mature to solid cortical attachment. On histologic
      examination, all lesions demonstrated 3 distinct components with variable degrees
      of representation: (1) hypercellular cartilage with calcification and
      ossification, with the calcified cartilage having a characteristic basophilic
      tinctorial quality; (2) cancellous bone undergoing maturation; and (3) spindle
      cell stroma without cytologic atypia. In 1 case with a long-standing history, the
      cartilaginous component was minimal. BPOP, together with florid reactive
      periostitis and turret exostosis, may represent different stages in the
      development of a posttraumatic proliferative process. BPOP apparently arises from
      the periosteal tissues through a process of cartilaginous metaplasia.

PMID- 12514791
TI  - Dural lesions mimicking meningiomas.
AB  - Recently, a number of neoplastic and nonneoplastic entities have been reported
      that radiographically and clinically mimic meningiomas. Because these lesions
      occur infrequently and may resemble a meningioma during intraoperative analysis,
      they may not be considered in the differential diagnosis. This review (and case
      illustrations) considers some of the newly recognized and notable lesions that
      can mimic meningiomas, including solitary fibrous tumors, gliosarcomas,
      leiomyosarcomas, hemangiopericytomas, melanocytomas, Hodgkin's disease,
      plasmacytomas, inflammatory pseudotumors, neurosarcoidosis, plasma cell
      granulomas, Rosai-Dorfman disease, Castleman's disease, xanthomas, rheumatoid
      nodules, and tuberculomas. Awareness that these lesions involve the dura may
      facilitate intraoperative recognition and, in some cases, preclude unnecessary
      additional surgery.

PMID- 12514792
TI  - CCR6 is a functional chemokine receptor that serves to identify select B-cell non
      Hodgkin's lymphomas.
AB  - Several recent studies have revealed important contributions of chemokines and
      their receptors to the development and progression of both hematopoietic and
      nonhematopoietic neoplasms. The chemokine receptor CCR6 is unusual in that it
      mediates leukocyte chemotaxis in response to a single chemokine, CCL20
      (macrophage inhibitory factor-3alpha), as well as in response to a family of
      antimicrobial peptides termed "beta-defensins." CCR6 is critical for mucosal
      immunity, and expression of the receptor is tightly regulated on hematopoietic
      cells. Here we characterize the expression of CCR6 on B cells and B-cell non
      Hodgkin's lymphomas. We demonstrate that CCR6 expression is limited to cells
      comprising the mantle and marginal zones of the secondary lymphoid tissues and
      serves to identify the majority of mantle cell, marginal zone, and mucosa
      associated lymphoid tissue lymphomas. Furthermore, we show that CCR6 serves as a
      functional chemokine receptor when expressed by neoplastic cells. Finally, we
      establish that the cognate ligand for CCR6 is present on mucosal epithelium
      infiltrated by neoplastic cells in select extranodal lymphomas. Thus, CCR6 is a
      useful new marker identifying a subset of B-cell non-Hodgkin's lymphomas and
      likely contributes to the localization of select extranodal lymphomas at mucosal
      sites.

PMID- 12514793
TI  - Urothelial carcinoma of the renal pelvis with choriocarcinomatous features:
      genetic evidence of clonal evolution.
AB  - Urothelial carcinoma with choriocarcinomatous features is a rare malignancy
      arising in the urinary bladder or renal pelvis. We report the case of a 60-year
      old man with a biphasic neoplasm of the right kidney composed of papillary
      urothelial carcinoma and choriocarcinoma. Widespread hepatic and pulmonary
      metastases with choriocarcinomatous features were found on autopsy 6 weeks after
      initial diagnosis. Chromosomal analysis revealed a close genetic relationship
      between the papillary urothelial and choriocarcinomatous tumor components,
      documenting for the first time that choriocarcinoma of the renal pelvis results
      from clonal evolution of urothelial carcinoma with acquisition of trophoblastic
      differentiation.

PMID- 12514794
TI  - Malignant granular cell tumor of the lateral femoral cutaneous nerve: report of a
      case with cytogenetic analysis.
AB  - Malignant granular cell tumors (MGCTs) are rare neoplasms of uncertain
      histogenesis. We report a case of MGCT involving a peripheral nerve with
      peritoneal and omental dissemination in which cytogenetic findings are available.
      Our results show that MGCTs share some cytogenetic abnormalities with malignant
      peripheral nerve sheath tumors (MPNSTs), supporting the hypothesis that they may
      represent histogenetically related lesions.

PMID- 12514795
TI  - Invasive papillary adenocarcinoma of the colon: is it really a distinct subtype?

PMID- 12514796
TI  - Onionskin-like pattern in inflammatory lesions of the gastrointestinal tract.

PMID- 12514797
TI  - GIST nomenclature.

PMID- 12514798
TI  - Telepathology overview.

PMID- 12514799
TI  - Optimizing chemotherapy by measuring reversal of P-glycoprotein activity in
      plasma membrane vesicles.
AB  - The appearance of multidrug resistance (MDR) of cancer cells is a major obstacle
      to successful chemotherapy. Several proteins have been identified that pump
      chemotherapeutic drugs out of cells, thus bringing about MDR. One representative
      pump is the P-glycoprotein, whose function can be inhibited by blockers (also
      known as reversers, modulators or chemosensitizers). In clinical application,
      many of these blockers are often not effective because they become bound to the
      plasma of the patients. The extent of plasma binding of the blocker varies in
      different persons and we have developed a 96-well kit to assay such inter-person
      differences. The assay uses membrane vesicles isolated from a human
      lymphoblastoid cell line (CEM Col1000). Uptake of rhodamine into the vesicles was
      measured with different concentrations of the blockers verapamil and XR9576 in
      presence of human plasma. The reverser XR9576 is nearly 30 times more effective
      than the classical blocker verapamil, the relevant K(m) values ranging from 2.66
      to 45 nM for XR 9576 and 0.7 to 5.5 microM for verapamil. An even greater
      difference between these two drugs, nearly 1,000-fold, could be shown also in
      intact cells by calcein AM uptake experiments.

PMID- 12514800
TI  - Synthesis of 3-tert-butylcatechol by an engineered monooxygenase.
AB  - Recombinant Escherichia coli JM101 was used for the in vivo biocatalytic
      synthesis of 3-tert-butyl- catechol. The bacterial strain synthesized the
      laboratory-evolved variant HbpA(T2) of 2-hydroxybiphenyl 3-monooxygenase (HbpA,
      EC 1.14.13.44) from Pseudomonas azelaica HBP1. The mutant enzyme HbpA(T2) is able
      to hydroxylate 2-tert-butylphenol to the corresponding catechol, a reaction that
      is not catalyzed by the wild-type enzyme. The biotransformation was performed in
      a 3-L bioreactor for 24 h. To mitigate the toxicity of the 2-tert-butylphenol
      starting material, we applied a limited substrate feed. Continuous in situ
      product removal with the hydrophobic resin Amberlite XAD-4 was used to separate
      the product from culture broth. In addition, binding to the resin stabilized the
      product, which was important because 3-tert-butylcatechol is very labile in
      aqueous solution. The productivity of the process was 63 mg L(-1) h(-1) so that
      after 24 h, 3.0 g of 3-tert-butylcatechol were isolated. Down-stream processing
      consisted of two steps. First, bound 2-tert-butylphenol and 3-tert-butylcatechol
      were eluted from Amberlite XAD-4 with methanol. Second, the two compounds were
      separated over neutral aluminum oxide, which selectively binds the produced
      catechol but not the phenol substrate. The final purity of 3-tert-butylcatechol
      was greater than 98%.

PMID- 12514801
TI  - Effect of deletion of chitin synthase genes on mycelial morphology and culture
      viscosity in Aspergillus oryzae.
AB  - The objective of this study was to quantify the effect of disrupting two chitin
      synthases, chsB and csmA, on the morphology and rheology during batch cultivation
      of Aspergillus oryzae. The rheological properties were characterized in batch
      cultivations at different biomass concentrations (from 3.4-22.5 g kg(-1) biomass)
      and the power-law model adequately described the rheological properties. In the
      cultivations there were pellets, clumps, and freely dispersed hyphal elements.
      The different morphological fractions were quantified using image analysis. The
      apparent viscosity of the fermentation broth was significantly affected by the
      biomass concentration, the morphology, and also by pH. The chsB disruption strain
      had lower consistency index K values for all biomass concentrations investigated,
      which is a desirable trait for industrial Aspergillus fermentations.

PMID- 12514802
TI  - DNA purification by triple-helix affinity precipitation.
AB  - Recent advances in DNA-based medicine (gene therapy, genetic vaccination) have
      intensified the necessity for pharmaceutical-grade plasmid DNA purification at
      comparatively large scales. In this contribution triple-helix affinity
      precipitation is introduced for this purpose. A short, single-stranded
      oligonucleotide sequence (namely (CTT)(7)), which is capable of recognizing a
      complementary sequence in the double-stranded target (plasmid) DNA, is linked to
      a thermoresponsive N-isopropylacrylamide oligomer to form a so-called affinity
      macroligand (AML). At 4 degrees C, i.e., below its critical solution temperature,
      the AML binds specifically to the target molecule in solution; by raising the
      temperature to 40 degrees C, i.e., beyond the critical solution temperature of
      the AML, the complex can be precipitated quantitatively. After redissolution of
      the complex at lower temperature, the target DNA can be released by a pH shift to
      slightly alkaline conditions (pH 9.0). Yields of highly pure (plasmid) DNA were
      routinely between 70% and 90%. Non-specific co- precipitation of either the
      target molecule by the non-activated AML precursor or of contaminants by the AML
      were below 7% and presumably due to physical entrapment of these molecules in the
      wet precipitate. Ligand efficiencies were at least 1 order of magnitude higher
      than in triple-helix affinity chromatography.

PMID- 12514803
TI  - Maillard reactions and increased enzyme inactivation during oligosaccharide
      synthesis by a hyperthermophilic glycosidase.
AB  - The thermostable Pyrococcus furiosus beta-glycosidase was used for
      oligosaccharide production from lactose in a kinetically controlled reaction. Our
      experiments showed that higher temperatures are beneficial for the absolute as
      well as relative oligosaccharide yield. However, at reaction temperatures of 80
      degrees C and higher, the inactivation rate of the enzyme in the presence of
      sugars was increased by a factor of 2 compared to the inactivation rate in the
      absence of sugars. This increased enzyme inactivation was caused by the
      occurrence of Maillard reactions between the sugar and the enzyme. The browning
      of our reaction mixture due to Maillard reactions was modeled by a cascade of a
      zeroth- and first-order reaction and related to enzyme inactivation. From these
      results we conclude that modification of only a small number of amino groups
      already gives complete inactivation of the enzyme.

PMID- 12514804
TI  - Alphavirus cDNA-based expression vectors: effects of RNA transcription and
      nuclear export.
AB  - The construction of layered DNA-RNA replicons has facilitated and expanded the
      use of alphavirus vectors to vaccine development, construction of packaging cell
      lines and long-term heterologous gene expression. In these vector systems, the
      alphavirus replicon is under the control of a strong RNA polymerase II promoter
      and replicon RNA is transcribed from DNA before transport to the cytoplasm.
      Efficient RNA amplification catalyzed by the viral replicase results in high
      levels of mRNA and the recombinant protein. Recently, we developed a temperature
      regulated Sindbis replicon-based DNA expression system characterized by a linear
      increase of expression upon decrease of the temperature from 37 degrees C to 29
      degrees C. Modifications known to affect transcription and nuclear export of RNA
      led to a 5-fold increase in expression in BHK cells and up to over 80-fold
      increase in CHO cells and BF fibroblasts in transient transfection experiments.
      Furthermore, reducing cell proliferation resulted in a further 2- to 3-fold
      higher expression. While increased expression per cell was responsible for some
      of the enhanced production, it was primarily the number of expressing cells that
      made the difference in most cell lines. Further experiments indicated that a
      threshold amount of replicon RNA had to reach the cytoplasm in order for
      replication to occur. Thus, alterations that improve transcription, nuclear
      export and stability of the RNA had a significant impact on protein production in
      the pCytTS expression system and probably in other layered DNA-based viral
      vectors. Furthermore the results indicate that RNA replication is differentially
      regulated in DNA layered RNA replicons versus viral infection.

PMID- 12514805
TI  - Microfluidic peroxidase biochip for polyphenol synthesis.
AB  - An enzyme-containing microfluidic biochip has been developed for the oxidative
      polymerization of phenols. The biochip consists of a simple T-junction with two
      feed reservoirs 20 mm apart and a microreaction channel 30 mm long. The channel
      is 15 microm deep and 200 microm wide at the center, giving a reaction volume of
      90 nL. The biochip was fabricated using conventional photolithographic methods on
      a glass substrate etched using a HF-based solution. Fluid transport was enabled
      using electroosmotic flow. Soybean peroxidase was used as the phenol oxidizing
      catalyst, and in the presence of p-cresol and H(2)O(2), essentially complete
      conversion of the H(2)O(2) (the limiting substrate) occurred in the microchannel
      at a flow rate of ca. 290 nL/min. Thus, peroxidase was found to be intrinsically
      active even upon dramatic scale-down as achieved in microfluidic reactors. These
      results were extended to a series of phenols, thereby demonstrating that the
      microfluidic peroxidase reactor may have application in high-throughput screening
      of phenolic polymerization reactions for use in phenolic resin synthesis.
      Finally, rapid growth of poly(p-cresol) on the walls of the microreaction channel
      could be performed in the presence of higher H(2)O(2) concentrations. This
      finding suggests that solution-phase peroxidase catalysis can be used in the
      controlled deposition of polymers on the walls of microreactors.

PMID- 12514806
TI  - Effect of nitrite and nitrate on in situ sulfide production in an activated
      sludge immobilized agar gel film as determined by use of microelectrodes.
AB  - Microelectrode, fluorescence in situ hybridization (FISH), and denaturing
      gradient gel electrophoresis (DGGE) analyses were used to investigate the effect
      of nitrite and nitrate on in situ sulfide production in an activated sludge
      immobilized agar gel film. Microelectrode measurements of O(2), H(2)S, NO(3)(-),
      NO(2)(-), and pH revealed that the addition of NO(2)(-) and NO(3)(-) forced
      sulfate reduction zones deeper in the agar gel and significantly reduced the in
      situ sulfide production levels. The sulfate reduction zone was consequently
      separated from O(2) and NO(2)(-) or NO(3)(-) respiration zones with increasing
      the concentrations of NO(2)(-) and NO(3)(-). These NO(2)(-) and NO(3)(-)
      treatments had only a transient effect on sulfide production. The in situ sulfide
      production quickly recovered to the previous levels when NO(2)(-) and NO(3)(-)
      were removed. The PCR-DGGE and FISH analyses revealed that 2-day-continuous
      addition of 500 microM NO(3)(-) did not change the metabolically active sulfate
      reducing bacterial (SRB) community. On the basis of these data, it could be
      concluded that the addition of NO(2)(-) and NO(3)(-) did not kill SRB, but
      induced the interspecies competition for common carbon source (i.e., acetate)
      between nitrate-reducing heterotrophic bacteria and SRB and enhanced the
      oxidation of the produced sulfide, which were main possible causes of the
      suppression of in situ sulfide production in the agar gel.

PMID- 12514807
TI  - Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes
      micropatterned on deformable elastomers.
AB  - Because cell shape and alignment, cell-matrix adhesion, and cell-cell contact can
      all affect growth, and because mechanical strains in vivo are multiaxial and
      anisotropic, we developed an in vitro system for engineering aligned, rod-shaped,
      neonatal cardiac myocyte cultures. Photolithographic and microfluidic techniques
      were used to micropattern extracellular matrices in parallel lines on deformable
      silicone elastomers. Confluent, elongated, aligned myocytes were produced by
      varying the micropattern line width and collagen density. An elliptical cell
      stretcher applied 2:1 anisotropic strain statically to the elastic substrate,
      with the axis of greatest stretch (10%) either parallel or transverse to the
      myofibrils. After 24 h, the principal strain parallel to myocytes did not
      significantly alter myofibril accumulation or expression of atrial natriuretic
      factor (ANF), connexin-43 (Cx-43), or N-cadherin (by indirect immunofluorescent
      antibody labeling and immunoblotting) compared with unstretched controls. In
      contrast, 10% transverse principal strain resulted in continuous staining of
      actin filaments (rhodamine phalloidin); increased immunofluorescent labeling of
      ANF, Cx-43, and N-cadherin; and upregulation of protein signal intensity by
      western blotting. By using microfabrication and microfluidics to control cell
      shape and alignment on an elastic substrate, we found greater effects for
      transverse than for longitudinal stretch in regulating sarcomere organization,
      hypertrophy, and cell-to-cell junctions.

PMID- 12514808
TI  - Uptake of macrominerals and trace elements by the cyanobacterium Spirulina
      platensis (Arthrospira platensis PCC 8005) under photoautotrophic conditions:
      culture medium optimization.
AB  - Uptake rates of macrominerals and trace elements were characterized in batch and
      continuous cultures of Spirulina platensis under photoautotropic conditions. The
      values of yield coefficients were determined using inductively coupled plasma
      emission spectroscopy (ICP-ES). Further simplifications of culture medium proved
      possible, mainly in the trace element solutions; concentrations of some elements
      were lowered and trace elements B, Mo, V, Cr, Ni, Co, W, and Ti were removed.

PMID- 12514809
TI  - Pattern identification and classification in gene expression data using an
      autoassociative neural network model.
AB  - The application of DNA microarray technology for analysis of gene expression
      creates enormous opportunities to accelerate the pace in understanding living
      systems and identification of target genes and pathways for drug development and
      therapeutic intervention. Parallel monitoring of the expression profiles of
      thousands of genes seems particularly promising for a deeper understanding of
      cancer biology and the identification of molecular signatures supporting the
      histological classification schemes of neoplastic specimens. However, the
      increasing volume of data generated by microarray experiments poses the challenge
      of developing equally efficient methods and analysis procedures to extract,
      interpret, and upgrade the information content of these databases. Herein, a
      computational procedure for pattern identification, feature extraction, and
      classification of gene expression data through the analysis of an autoassociative
      neural network model is described. The identified patterns and features contain
      critical information about gene-phenotype relationships observed during changes
      in cell physiology. They represent a rational and dimensionally reduced base for
      understanding the basic biology of the onset of diseases, defining targets of
      therapeutic intervention, and developing diagnostic tools for the identification
      and classification of pathological states. The proposed method has been tested on
      two different microarray datasets-Golub's analysis of acute human leukemia [Golub
      et al. (1999) Science 286:531-537], and the human colon adenocarcinoma study
      presented by Alon et al. [1999; Proc Natl Acad Sci USA 97:10101-10106]. The
      analysis of the neural network internal structure allows the identification of
      specific phenotype markers and the extraction of peculiar associations among
      genes and physiological states. At the same time, the neural network outputs
      provide assignment to multiple classes, such as different pathological conditions
      or tissue samples, for previously unseen instances.

PMID- 12514810
TI  - Simulation of growth and detachment in biofilm systems under defined hydrodynamic
      conditions.
AB  - Detachment from biofilms was evaluated using a mixed culture biofilm grown on
      primary wastewater in a tube reactor. The growth of biofilms and the detachment
      of biomass from biofilms are strongly influenced by hydrodynamic conditions. In a
      long-term study, three biofilms were cultivated in a biofilm tube reactor. The
      conducted experiments of biofilm growth and detachment can be divided into three
      phases: 1) an exponential phase with a rapid increase of the biofilm thickness,
      2) a quasi-steady-state with spontaneous fluctuation of the biofilm thickness
      between 500 and 1,200 microm in the investigated biofilm systems, and 3) a
      washout experiment with increased shear stress in three to four steps after
      several weeks of quasi-steady-state. Whereas the biofilm thickness during the
      homogeneous growth phase can be regarded constant throughout the reactor, it was
      found to be very heterogeneous during the quasi-steady-state and the washout
      experiments. Growth and detachment during all three phases was simulated with the
      same one-dimensional biofilm model. For each of the three phases, a different
      detachment rate model was used. During the homogeneous growth phase, detachment
      was modeled proportional to the biofilm growth rate. During the quasi-steady
      state phase, detachment was described by random detachment events assuming a base
      biofilm thickness. Finally, the washout experiment was simulated with detachment
      being a function of the biofilm thickness before the increase of the shear
      stress.

PMID- 12514811
TI  - Composite surface for blocking bacterial adsorption on protein biochips.
AB  - The design and fabrication of protein biochips requires characterization of
      blocking agents that minimize nonspecific binding of proteins or organisms.
      Nonspecific adsorption of Escherichia coli, Listeria innocua, and Listeria
      monocytogenes is prevented by bovine serum albumin (BSA) or biotinylated BSA
      adsorbed on SiO(2) surfaces of a biochip that had been modified with a C(18)
      coating. Biotinylated BSA forms a protein-based surface that in turn binds
      streptavidin. Because streptavidin has multiple binding sites for biotin, it in
      turn anchors other biotinylated proteins, including antibodies. Hence,
      biotinylated BSA simultaneously serves as a blocking agent and a foundation for
      binding an interfacing protein, avidin or streptavidin, which in turns anchors
      biotinylated antibody. In our case, the antibody is C11E9, an IgG-type antibody
      that binds Listeria spp. Nonspecific adsorption of another bacterium, Escherichia
      coli, is also minimized due to the blocking action of the BSA. The blocking
      characteristics of BSA adsorbed on C(18)-derivatized SiO(2) surfaces for
      construction of a protein biochip for electronic detection of pathogenic
      organisms is investigated.

PMID- 12514812
TI  - Cell-type-specific adhesion onto polymer surfaces from mixed cell populations.
AB  - The targeted adhesion of a specific cell type from a mixed cell suspension via
      the surface presentation of a cell-specific ligand is demonstrated. This generic
      strategy is illustrated by the covalent attachment of a galactose derivative to a
      polylysine backbone via the amine functionality. Following adsorption of the
      resultant material to a polymer surface, hepatocyte adhesion is increased via the
      interaction between galactose and asialoglycoprotein receptors in a concentration
      dependent manner. The selective nature of the material is demonstrated by the
      approximate doubling in the adhesion of hepatocytes relative to a nontargeted
      cell type (hepatic stellate cells), and an inability of the modified polymer
      surface to attract additional numbers of the nontargeted cells. This strategy
      provides a mechanism for controlling the ratios of cell types adhering to
      scaffold supports, thus enabling the rapid creation of defined coculture systems
      from heterogeneous cell suspensions.

PMID- 12514813
TI  - How to culture a wound.

PMID- 12514814
TI  - Study finds RSV #1 cause of hospitalization for children under one.

PMID- 12514815
TI  - Leading nursing organizations unveil new immunization survey findings.

PMID- 12514816
TI  - [REBEn: 70 years in the social building of knowledge of nursing in Brazil].

PMID- 12514817
TI  - [REBEn: Good grief! If everybody were like you at 70 years of age!].
AB  - In this article the author reports on the importance of Revista Brasileira de
      Enfermagem-REBEn (Brazilian Journal of Nursing) for her educational trajectory
      since the undergraduation course until the present days. She describes her
      personal, professional and educational development, as well as the development of
      her scientific curiosity, relating it to the knowledge acquired in the periodical
      REBEn.

PMID- 12514818
TI  - [Brazilian Association of Nursing -- 1926-1976: historical overview].

PMID- 12514819
TI  - [Rachel Haddock Lobo: her professional life and her contribution to REBEn].
AB  - This is a historical study that analyses the formation process of the
      professional habitus of Rachel Haddock Lobo through the reconstruction of her
      biography. It also analyses her contribution as 1st editor in chief of Revista
      Annaes de Enfermagem (Brazilian Journal of Nursing), in 1932, which is currently
      called Revista Brasileira de Enfermagem. The preferential primary sources of this
      study included written documents and the oral testimony of one of Rachel Haddock
      Lobo's family members. Both sources were obtained from Centro de Documentacao da
      Escola de Enfermagem Ana Nery (Documentation Center of Ana Neri School of
      Nursing). Data were analyzed through the concepts of habitus and social
      configuration by Norbert Elias. The analysis showed that Rachel Haddock Lobo gave
      expressive contribution to the creation process of the journal referred, which,
      on its turn, had an strategic importance on the formation of the identity of the
      Brazilian nursing professionals at that time.

PMID- 12514820
TI  - [REBEn in the context of the history of Brazilian nursing: the significance of
      remembering Dr. Glete de Alcantara].
AB  - This is a Social History study which aims at recuperating the professional
      trajectory of Glete de Alcantara in the Revista Brasileira de Enfermagem/REBEn
      (Brazilian Journal of Nursing), initially called Anais de Enfermagem. It is based
      on the concept of memory of Maurice Halbwach, and on the concept of generation of
      Daniel Pecaut. The study contextualizes the professional development of Glete de
      Alcantara in the history of the Brazilian nursing, highlighting the creation of
      the Nursing School of the University of Sao Paulo (EERP/USP) in Ribeirao Preto.
      The sources for the study were documents obtained in the Centro de Memoria da
      Escola de Enfermagem (Memory Center of the School of Nursing) of Ribeirao Preto
      and in ABEN (Brazilian Association of Nursing) in Brasilia. Data obtained in this
      association were mainly collected from its record books the journals.

PMID- 12514821
TI  - [Haydee Guanais Dourado: charisma and personality to the service of an ideal].
AB  - This is a descriptive-social study which looks at the performance of Haydee
      Guanais Dourado (HGD) in the Brazilian nursing scene, in the mid-20's. The
      objectives are to describe her personal and professional profile; analyze her
      participation in ABEn (Brazilian Association of Nursing) and discuss the
      relationship between her attributes and her contribution to the development of
      nursing in Brazil. The sources used consisted of Revista Brasileira de Enfermagem
      REBEn (Brazilian Journal of Nursing), written documents and oral reports obtained
      from the Documentation Center of Anna Nery Nursing School in the Federal
      University of Rio de Janeiro. The analysis and the interpretation of the data
      were made by means of the triangulation of the primary and secondary sources, and
      the historical contextualization. The study evidenced the singularity of HGD and
      the importance of her contribution to the institutionalization of the nursing
      profession in the Brazilian society.

PMID- 12514822
TI  - [Editorials of REBEn: Expression of Brazilian nursing life].

PMID- 12514823
TI  - [The Revista Brasileira de Enfermagem: presenting perspectives for its analysis].
AB  - This essay proposes a reflection on different perspectives for analyzing the
      Brazilian Journal of Nursing. The journal, which is considered an instrument for
      the diffusion of knowledge and ideology of the nursing field, has been the object
      of few studies. In this essay, the authors adopt as theoretical reference the
      signification triangle of Pierre Levy and aspects of the feminist theory. The
      authors believe the journal should be analyzed as an object that produces, in its
      relation with nursing professionals, elements that constitute a culture,
      knowledge and symbology of the Brazilian nursing.

PMID- 12514824
TI  - [Beliefs about nursing in the Revista Brasileira de Enfermagem: reflections on
      ideals, science, and art].
AB  - The inquiry of this study is the beliefs related to the nursing professional in
      the first decades of this activity in Brazil. The investigation presupposes that
      some of these beliefs are still current. The objective is to point out the
      beliefs expressed by Revista Brasileira de Enfermagem (Brazilian Journal of
      Nursing) in 33 articles, during the period between 1932 (when the journal was
      created) and 1954. Five notions of the nursing professional were identified
      through the analyses of the symbology presented on the cover of the periodical-
      Egyptian mythology; ideal, science and art, inscribed in a triangle. The
      categories established for nurses were: self-forgetful, heroine, socially
      committed, mercenary and bad angel. Finally, the study proposes an interpretation
      to the ideas presented in the triangle.

PMID- 12514825
TI  - [Developing knowledge and a profession: 70 years of the Revista Brasileira de
      Enfermagem].
AB  - Revista Brasileira de Enfermagem-REBEn (Brazilian Journal of Nursing) is now 70
      years old. It was created in 1932, and was initially called Anais de Enfermagem.
      Its main purpose was to be a communication link among Brazilian professionals of
      nursing. REBEn, which is directly linked to ABEn (Brazilian Association of
      Nursing), also has as its objective the publicizing of scientific production in
      different fields of knowledge which can be of interest for the nursing
      profession. The journal went through many difficulties before achieving the
      current status of most important publishing in the field of nursing in Brazil.
      The periodical was developed along many generations and has now achieved
      intellectual maturity which guaranteed its inclusion in the international
      indexation of scientific periodicals.

PMID- 12514826
TI  - [Counterpoint among personalities of the Brazilian Nursing Congresses and of the
      Revista Brasileira de Enfermagem from 1977 to 1987].
AB  - This is a qualitative study, using an exploratory approach, which has as its main
      aim to analyze and counterpoint central issues and personalities of the Brazilian
      Nursing Conferences and the editorials of the Brazilian Nursing Journal, from
      1977 to 1987. It was analyzed 09 annuals and 24 editorials. The results show that
      the contents were aligned with the policy of the central ABEn. The leadership of
      Ana Nery School and USP Nursing School is evident in this period. Male nurses had
      no expressive participation in the nursing conferences, except those who were
      members of the PARTICIPACAO movement. We found only one editorial written by a
      male nurse. We observed changes in the central ABEn policy after 1984 provoked by
      the PARTICIPACAO movement and, influencing the change of subjects at the
      conferences, and the editorials of the REBEn.

PMID- 12514827
TI  - [Preparing the awakening of Lilith: gender in nursing in articles of REBEn in th
      80s and 90s].
AB  - This study presents an analysis of the conditions of women/nurses in the articles
      published by REBEn (Brazilian Journal of Nursing) in the 1980's and 1990's.
      Initially, the researcher intended to analyze specifically those articles which
      had some reference to gender. However, in the beginnings of the 1980's, some
      articles pointed in the direction of the social problems involving women and the
      implication of these problems to nurses, without making explicit reference to
      gender category. Thus, the author decided to evaluate abstracts and the content
      of different articles, in order to detect those which were related to the subject
      of investigation. Eleven articles and two thematic editorials selected show that
      REBEn, although timidly, is a magazine which is updated regarding decisive
      moments of women's worldwide movement.

PMID- 12514828
TI  - [Nursing education through REBEn: 1990-2001].
AB  - This paper looks at the scientific production of nursing professionals, on the
      subject of education in nursing, published in REBEn (BRAZILIAN JOURNAL OF
      NURSING) between 1990-2001. It aims at identifying articles on education in
      nursing and analyzing the levels and sub-themes in 168 articles obtained from 43
      magazines. Results showed that undergraduation teaching was the most highlighted
      theme, followed by education for health and continued education. There was less
      attention to the theme education (in general), post-graduation and High School
      Education. The study concluded that, in the last decade, Brazilian nursing has
      reflected upon curriculum changes, which were conquered by its professionals;
      valued its educational role through privileging education in health and
      highlighted continued education due to technological advances.

PMID- 12514829
TI  - [The use of REBEn as source in 2 strict sense programs the city of Rio de
      Janeiro].
AB  - This paper is concerned with the use of REBEn (Brazilian Journal of Nursing) in
      dissertations and theses produced in two public programs in Rio de Janeiro.
      OBJECTIVES: 1) to investigate the impact of this journal in the production of the
      knowledge in the field of nursing from 1992 to 2001, and 2) to analyze,
      comparatively, the use of the journal in theses and dissertations. Document
      analysis was done, based on bibliographical references. Data were analyzed
      quantitatively. The study demonstrated that REBEn remains an important
      publication for the development scientific knowledge in the nursing field.
      Approximately 50% of the authors cite it in dissertations, and 60% cite it in
      theses. Literature revision was numerically smaller in dissertations compared to
      theses. Regarding theses, 1995 was the year in which there were more references
      from REBEn.

PMID- 12514830
TI  - [CAPES' assessment: a contribution to the improvement of nursing journals?].

PMID- 12514831
TI  - [Nursing assistance and home care in antineoplastic chemotherapy].
AB  - This paper is the result of our experience in clinical oncology in which we
      verified the lack of systematization in the nursing assistance offered to
      oncological patients. Thus, the objectives of this study are to analyze the
      problems of patients undergoing antineoplasic chemotherapy; identify the need for
      home nursing care; implement a systematic home assistance in order to continue
      the post-chemotherapy care and analyze the proposal of a systematic assistance.
      It was concluded that a specialized, systematic, whole, continuous and holistic
      assistance, extended to the patients' homes, minimizes complications associated
      to the side effects of antineoplasic chemotherapy.

PMID- 12514832
TI  - [Evaluation of the technique of subcutaneous administration of heparin in the
      development of hematomas].
AB  - This study identified and evaluated the presence and extent of hematomas, pain
      and other complications after the administration of low-dose subcutaneous
      heparin. It compared applications using the conventional technique and
      applications with modified techniques in 60 patients hospitalized in an
      University Hospital in the interior of Sao Paulo State-Brazil. Each patient
      received four heparin injections, that is, two injections of each of the
      techniques mentioned. The site was observed after 24 hours. Results showed that
      hematomas were observed after the application of 83.7% of the injections. The
      thigh was the site with the highest incidence of hematomas, followed by the arm
      and the abdomen. There were no significant differences in the formation of
      hematomas caused by the two techniques. It was concluded that the techniques used
      for heparin application were probably not related to the formation of hematomas.

PMID- 12514833
TI  - [Self-care and the asthmatic adult: systematization of nursing care].
AB  - This research aims at the systematization of nursing assistance under Orem's
      nursing theory of self-care deficit. In order to conduct this study, the
      convergent approach was used through the performance of the nursing processes in
      an adult with asthma. Interviews, physical examinations, observations, data
      record, observation of nursing assistance in policlinics along with home visits
      were the techniques used to gather data. After the observation of the nursing
      assistance, self-care deficits were identified and a new assistance plan and
      objectives were established, as well as a system and methods of support. The
      assistance plan was performed through the implementation of nursing assistance,
      prioritizing educational support. Based on the results, it was concluded that the
      application of the nursing processes through Orem's self-care referential is
      feasible and necessary for the engagement of clients and their family in self
      care.

PMID- 12514834
TI  - [Perception of clients when receiving home care].
AB  - This qualitative and exploratory study analyzed the perception of users of the
      Home Care Program (SSS-GHC) in Porto Alegre, Rio Grande do Sul state regarding
      the assistance provided by its interdisciplinary team and caretakers. Among the
      17 clients interviewed, there was a prevalence of women, elderly people and
      chronic degenerative disease patients. As a result of the analysis it was
      possible to identify five categories which were related to family, professional
      care and experiences of the subjects in relation to life circumstances. Results
      showed that, according to the client's point of view, the care received was
      viewed as humanized and favorable to the evaluative strategy of the Program.

PMID- 12514835
TI  - [Implementation of the teaching-learning strategy for the chronic patient's
      family].
AB  - This study aims at implementing the teaching-learning strategy for families of
      patients in chronic conditions. It considers the importance of evaluating the
      needs and abilities of family members in order to prepare them to manage that
      situation appropriately, as well as to be able to provide adequate home care. A
      diagnostic evaluation of a family member/caretaker was conducted during the
      hospitalization of a patient with congestive cardiac insufficiency. During the
      diagnosis "knowledge deficit" was identified. Thus, a teaching plan was
      elaborated for such caretaker with the purpose of preparing him/her for home
      care. During implementation, formative evaluations were conducted with the
      purpose of learning about the efficacy of the strategies employed and the
      summative in the patient's home. The importance of nurses' resorting to the
      teaching-learning strategy in order to guide the family member/caretaker in the
      process of caring for people with chronic conditions was certified. The aim is
      promoting life, in spite of the disease, since the quality of such care will
      prevent aggravating recurrence and consequent re-hospitalizations.

PMID- 12514836
TI  - Maternal mode of living and child health.
AB  - In this article, maternal mode of living is investigated, examining both
      socioeconomic conditions and lifestyle factors, in order to identify to what
      extent health policies are tangibly meeting the needs of low income Brazilian
      mothers and children. Data are derived from unstructured interviews with 17
      mothers with children under age 6, residing in the Federal District, Brazil.
      Their stories reveal a life marked by economic difficulties and inadequate living
      conditions, aggravated by early reproductive behavior, confinement to the home
      and no leisure. Although they have access to primary health care, the quality is
      inadequate. Increased awareness to the mother's situation is necessary in order
      to improve the health of young children.

PMID- 12514837
TI  - [Perception of health managers regarding collective health care].
AB  - This study aims at identifying the perception of managers and administrators of
      health care services, concerning the health care provided by the public health
      sector within SUS in the Federal District. This is a qualitative research in
      which the data was obtained through semi-structured interviews with health
      management professionals. It was concluded that the implementation of guidelines
      developed by the SUS still represents a challenge for the community and health
      care workers alike. In short, these two entities must coordinate their efforts in
      order to implement strategies designed at improving the health service provided
      to population.

PMID- 12514838
TI  - [Critical aspects in nursing scientific production -- papers presented to REBEn].
AB  - This is an exploratory descriptive study which aims at detecting critical aspects
      of the manuscripts submitted to REBEn (Brazilian Journal of Nursing) for
      publishing. Data was collected through the evaluation instruments used by the
      Editorial Board of REBEn on the selection of articles for the journal. Thirty-two
      evaluation reports, which represent 50% of the articles published in one volume
      of the journal, were analyzed. Results showed that most of the articles accepted
      for publishing were deficient, needed correction and that the authors needed
      guidance regarding requirements for publishing, such as peer review. Another
      problem detected was that the authors of the articles submitted did not seem to
      know the norms of presentation of the journal.

PMID- 12514839
TI  - [Practice in epidemiologic surveillance: between the general and the specific].
AB  - This study analyses the perspectives of the organization of epidemiological
      surveillance (ES) in two kinds of organizations. The first is a set of
      undifferentiated practices; the second is a set of specific practices carried out
      in the local health system of Ribeirao Preto, Sao Paulo Federal State. Both
      organizations are described in general terms and discussed according to the view
      of local health professionals and professionals of the epidemiological
      surveillance. This study presupposes that the decentralization should be
      supported by discussions regarding forms of organization among the groups
      involved in it. The guiding concepts of this research are nuclei and field of
      competence and responsibility. Seventeen professionals were the subjects of this
      study. Eleven participants were nurses and six were managers of the municipal
      health department of Ribeirao Preto. Data was obtained from documents and semi
      structured interviews, which were analyzed through the method of content
      analysis, theme modality. The theme "the epidemiological surveillance practice:
      between the general and the specific" was created according to the following
      signification nuclei: specific and general knowledge, and collective actions.

PMID- 12514840
TI  - [The theme as intersubjectivity possibility -- the choice of the nursing journal:
      text and context].
AB  - The present study is a descriptive and exploratory research which has as its
      objective accomplishing a critical analysis of the magazine "Texto e Contexto
      Enfermagem" (Nursing--Text and Context), as a thematic option. Eighteen issues of
      the magazine, published between 1992 and 2000, were analyzed. Two instruments
      were used to evaluate the inter-relation of the themes with the lines of research
      of the Post Graduation Program of Nursing in the Federal University of Santa
      Catarina (PEN/UFSC) in Brazil; the type of articles published; and the origin and
      profile of the authors of the magazine. It was verified that: the themes in the
      magazine are linked to the lines of research of PEN/UFSC; the average of articles
      published per issue is 23.88%; the majority of the articles are reflections and
      researches; most of the authors have a masters or doctors degree and do not teach
      at UFSC; and the rejection rate of the articles was 11.86%. The magazine bears
      most of the essential and complementary criteria established by CAPES and has
      great acceptance of among the Brazilian scientific community, since it brought a
      new dimension to the health care publications.

PMID- 12514841
TI  - Are submissive nurses ethical?: reflecting on power anorexia.
AB  - We believe that the notion of power anorexia, which we define as a lack of desire
      to exercise power, is central to reflections about nursing ethical concerns.
      Questioning the assumption that nurses are powerless, we argue that nurses can
      and do exercise power and that their actions and inactions have consequences not
      only for themselves, but also for those for whom they care. We propose that a
      feminist ethics perspective be used both to understand and to overcome nurses'
      power anorexia. Feminist thinkers remind us not only of oppression's
      psychological impact, but that stereotypical views about women are socially
      constructed and, therefore, can be changed. Nurses using this framework should
      explore the implications of a centralized notion of caring to the way we conceive
      of power relations in health care. Perhaps deconstructing caring by focusing on
      how nurses exercise power could help us to re-conceptualize nursing and promote
      new agendas for health and health care.

PMID- 12514842
TI  - [How to integrate humanization and technology in nursing training].
AB  - This paper discusses the current incorporation of the subject of humanization of
      care in the current context of Brazilian nursing. The relation between nursing
      and technology is approached, in this study, from a historical perspective. The
      study also develops the proposition of "human re-signification", having as
      reference the concept of Cyborg, considering the way this concept has been
      employed in the contemporary cultural and feminist theoretical framework.

PMID- 12514843
TI  - [Health policies and the humanization of care].
AB  - This essay consists of a reflection on the theme proposed on the 63rd Brazilian
      Nursing Week. It was initially elaborated for a conference, which would be
      presented in a commemorative nursing event. The essay relates the theme
      "humanization and work: reason and signification in nursing" to the current
      health policies implemented in Brazil. It discusses the consequences of these
      policies, and approaches strategies for the humanization of assistance.

PMID- 12514844
TI  - [Continuing education of graduate students: a commitment of the university?].
AB  - The objective of this study is to reflect on the role of the university as a
      fomenter of continued education, during and after undergraduation, according to
      the referential of Paulo Freire. Thus, it is necessary to rescue and indicate as
      a goal the integration of teaching, research and extension, as well as the
      construction of an institutional culture committed to continued education and the
      development of partnerships and support group for egressed students.

PMID- 12514845
TI  - [(Re)configuration of the nursing field in the new state (1937-1945)].
AB  - The subject of this study is the changes the nursing field went through during
      the period called Novo Estado. OBJECTIVES: Analyze the nursing environment in the
      Federal Capital during the period mentioned; discuss the effects of the influence
      of the Catholic Church and nurses of the American government in the Brazilian
      nursing environment. SOURCES: Documents obtained from the Documentation Center in
      Anna Nery/UFRJ School of Nursing and from literature on the topic. The
      interpretation of the findings was based on the Theory of the Social World by
      Pierre Bourdieu. Results showed deep changes in terms of professional education,
      labor market and institutionalization of the nursing assistance in a period
      (after the World War II) in which the Catholic Church and the United States had
      increased their power and influence. This new context determined the
      reconfiguration of the identity of Brazilian nurses and of the nursing field.

PMID- 12514846
TI  - [Facets of amputation -- a first approximation].
AB  - When participating in the project "The theme of the death as a way of access to
      the scientific initiation", I had the opportunity of approaching the phenomenon
      of death in its various facets. This contact provoked questionnings regarding
      amputation and how it was represented by those who experienced it, since it is
      considered a loss, similarly to death. Through scientific literature it was
      possible to understand the subject from different points of view, especially from
      the philosophical view of Merleau Ponty. It was observed that there was a lack of
      knowledge on the part of the nursing professionals. Thus, this study considers
      the perspective of those who experience amputation. In this sense, phenomenology
      may indicate a way of comprehending this phenomenon.

PMID- 12514847
TI  - Humanized assistance to women during delivery: a proposal to recover its
      singularity.

PMID- 12514848
TI  - Adequate nutrition creates positive outcomes and improves quality of life.

PMID- 12514849
TI  - Registered dieticians are your link to nutrition and cancer information.

PMID- 12514850
TI  - The art and science of nursing combine through nutritional interventions.

PMID- 12514851
TI  - The orthodontic generation gap.

PMID- 12514852
TI  - Imaging in othodontics: present and future.

PMID- 12514853
TI  - 2002 JCO study of orthodontic diagnosis and treatment procedures. Part 2.
      Breakdowns of selected variables.

PMID- 12514854
TI  - Bite opening with the Guray Bite Raiser.

PMID- 12514855
TI  - Impacted incisors with dilacerated roots.

PMID- 12514856
TI  - Indirect bonding with a flowable light-cured adhesive.

PMID- 12514857
TI  - The Ray Set: a new technique for precise indirect bonding.

PMID- 12514858
TI  - [Nursing. An ongoing challenge].

PMID- 12514859
TI  - [Drainage bag with pump ball. A new and effective aid for improved nursing care
      of gastric drainage].

PMID- 12514860
TI  - [Accidental falls in the hospital--patients injured by falls in the hospital. A
      challenge for nursing].

PMID- 12514861
TI  - [Current EMNID survey on peripheral arterial occlusive disease].

PMID- 12514862
TI  - [Risk of infection and infection control].

PMID- 12514864
TI  - [Mobile geriatric nurses under ongoing stress].

PMID- 12514863
TI  - [GlaxoSmithKline again lowers prices of drugs for HIV/AIDS and malaria].

PMID- 12514865
TI  - [Deficient rate of influenza vaccination of medical personnel is a risk for
      patients].

PMID- 12514866
TI  - [Chemotherapy protocol with taxol increase survival by 31 percent].

PMID- 12514867
TI  - [ORBIS personnel schedule with new automated schedule planning].

PMID- 12514868
TI  - [Unemployed because of epilepsy? Interrupting the vicious cycle].

PMID- 12514869
TI  - [Treatment of schizophrenia with "atypical antipsychotic drugs". Quality of life
      as a measure of treatment success].

PMID- 12514870
TI  - [Prevention of decubitus ulcers. 1].

PMID- 12514871
TI  - [Effectiveness of back bandages is ascertained].

PMID- 12514872
TI  - [Cost conscious hand disinfection].

PMID- 12514874
TI  - [Detective work in convent libraries].

PMID- 12514873
TI  - [Promoting wound healing in ulcus cruris].

PMID- 12514875
TI  - Nurse practitioners improving outcomes.

PMID- 12514876
TI  - Enrolled nurse training provides new opportunities.

PMID- 12514877
TI  - A psychiatric nurse muses about mental health.

PMID- 12514878
TI  - Respecting nurses working in different practice areas.

PMID- 12514879
TI  - Ministry assures fluoridation safety and effectiveness.

PMID- 12514880
TI  - Complying with New Zealand's restraint standards.

PMID- 12514881
TI  - CanTeen appeals for medical volunteers.

PMID- 12514882
TI  - New regulations for health professionals.

PMID- 12514884
TI  - Damning report from Health and Disability Commissioner.

PMID- 12514883
TI  - Workforce committee to consult health workers.

PMID- 12514885
TI  - Proving the effectiveness of nurse practitioners.

PMID- 12514886
TI  - Examining the culture of palliative care.

PMID- 12514887
TI  - Nurse prescribing lessons from the US.

PMID- 12514888
TI  - When will New Zealand nurses begin prescribing?

PMID- 12514889
TI  - Nursing and pharmacy--a clash of professional values.

PMID- 12514890
TI  - Theatre fire prompts review of safety protocols.

PMID- 12514891
TI  - Dissecting a brave new nursing world.

PMID- 12514892
TI  - The nurse practitioner role: a process of evolution.

PMID- 12514893
TI  - Blinded by nitrous oxide.

PMID- 12514894
TI  - Linking nursing and patient outcomes.

PMID- 12514895
TI  - The 'small' things count in caring.

PMID- 12514896
TI  - Nurses' role not well understood.

PMID- 12514897
TI  - Council forum updates nurses and midwives.

PMID- 12514898
TI  - The journey to privatisation.

PMID- 12514899
TI  - [Pneumatization of the mastoid process in medieval and contemporary skulls in
      light of radiologic and anthropometric measurements].
AB  - Pneumatization and morphogenesis of the temporal mastoid process take place
      concurrently and exhibit noticeable variability. The mastoid process is
      phylogenetically the youngest part of the skull. The aim of this work was to
      examine the pneumatization of the mastoid process in mediaeval and contemporary
      skulls using radiological and anthropometric methods. 85 male skulls from the
      second half of the 20th century were compared with 102 male and 50 female skulls
      from the Middle Ages. Bilateral X-ray images of mastoid processes according to
      Schuller were obtained and anthropometric measurements were done. Planimetry was
      used to obtain the air cell area of the mastoid processes. Correlations between
      several parameters of the temporal bone, facial bones, cranial bones and
      pneumatization of the mastoid process were studied. X-ray images revealed four
      types of the mastoid process: pneumatic, mixed, sclerotic, and apneumatic. The
      pneumatic mastoid process prevailed in every group of skulls. The mixed type was
      the least frequent in mediaeval female skulls and most frequent in contemporary
      male skulls. The apneumatic type was the rarest one in all groups of skulls. The
      largest surface area of mastoid air cell system was found in contemporary male
      and the smallest in mediaeval female skulls (Fig. 5). An asymmetry between left
      and right processes was observed in mediaeval and contemporary skulls, being more
      evident in the latter. No correlation was found between anthropometric parameters
      of the skull and the extent of pneumatization of the mastoid process.

PMID- 12514900
TI  - [Model experiments of physiologic and pharmacologic interactions with epithelial
      ionic currents induced by stimulation of sensory receptors ].
AB  - The present experiments were conducted to reveal regulatory mechanisms that
      control the stable electric potential (PD) and reversible changes in this
      potential during mechanical stimulation (dPD). The aim of the present work was to
      determine the role of C fibre endings and adrenergic and cholinergic receptors in
      the regulation of ion transport and to assess the applicability of frog skin as a
      model for physiological and pharmacological analysis of sodium and chloride
      currents. The experimental material consisted of 413 fragments of frog skin from
      139 animals. Cross-epithelial electric potential (PD in mV) and electric
      resistance (R in ohms) of isolated frog skin placed in Ussing apparatus were
      measured. Mechanical stimulation of sensory receptors resulted in reversible
      hyperpolarisation (Tab. 1, Fig. 1). Preincubation of frog skin in the presence of
      amiloride (AMI) completely inhibited this reaction (Tab. 1, Fig. 2a), whereas
      incubation in bumetanide (BUME) lowered PD and did not induce hypersensitivity to
      mechanical stimuli (Tab. 1). Addition of capsaicin (KAPSA) to the preparations
      incubated in Ringer's solution (RH) and in Ringer's solution reinforced with BUME
      resulted in depolarisation (Tab. 1). On the other hand, incubation with KAPSA
      caused hyperpolarisation in the AMI group. KAPSA supplementation influenced the
      sensitivity to mechanical stimulation in all experimental groups. It was found
      that ambroxol (ABX) added to the preparations incubated in RH solution and in
      BUME, inhibited the hyperpolarisation and did not affect the magnitude of the
      reaction in the AMI group (Tab. 2, Fig. 3). ABX administration caused a decrease
      in the reactivity to mechanical stimuli in the RH group. Blocking of both
      adrenergic and cholinergic receptors with a solution containing thymolol,
      benextramine, hexamethonium, and atropine (ABHT) inhibited the hyperpolarisation
      in all groups studied and was without effect on the magnitude of mechanical
      stimulation in AMI and BUME groups (Tab. 2). In the RH group, ABHT weakened the
      reaction to mechanical stimulation. Changes in the pH of Ringer's solution (pH
      6.4) caused a decrease in the electric potential and in the reactivity to
      mechanical stimuli, without altering resistance (Tab. 3). Addition of toluene
      diisocyanate (TDI) to preparations incubated in RH solution and in AMI increased
      the hyperpolarisation (Tab. 4). TDI also led to changes in the reaction to
      mechanical stimulation, i.e. induced depolarization in both groups. On the other
      hand, TDI administration to frog skin incubated with BUME did not cause any
      reaction change. The following conclusions were drawn from the present findings:
      1. Hyperpolarisation caused by physiological and pharmacological stimuli is
      effected principally through increased sodium flux. 2. Stimulation of C fibre
      endings, as well as of adrenergic and cholinergic receptors, inhibits ion
      transport. 3. Isolated frog skin is a useful model for studying sodium and
      chloride transport through mammalian epithelium.

PMID- 12514901
TI  - [Levels of lead and cadmium in pregnant women and newborns and evaluation of
      their impact on child development].
AB  - This study was done in 83 mothers and their 83 newborns with the aim of
      determining the levels of lead and cadmium in maternal venous and umbilical cord
      blood. Hair levels were also measured in 60 mothers and 14 newborns. The course
      of pregnancy was normal in each case and all deliveries were by natural forces at
      the Department of Obstetrics and Gynecology, Hospital in the City of Szczecin.
      The mean age of mothers was 26 and the postpartum Apgar score of each child was
      normal. The relationship between levels of lead and cadmium in blood and hair of
      mothers and newborns was examined and their influence on the general health
      status of the newborn was assessed, in particular on the body weight and length,
      head and chest circumferences. The influence of socio-economic conditions on
      levels of lead and cadmium in blood and hair of mothers and newborns was also
      examined. Levels of the two toxic metals in blood and hair were determined by
      means of atomic absorption spectrometry done in reference laboratories. The
      results were statistically compared taking the level of significance as p = 0.05.
      It was found that levels of lead and cadmium are lower in mothers and newborns
      from Szczecin than values reported by Polish and international investigators and
      are markedly below the upper permissible limit. Levels of lead and cadmium in
      maternal venous blood were 0.133 mumol/L (2.75 micrograms/dL) and 0.008 mumol/L
      (0.09 microgram/dL), respectively, and were significantly higher than levels in
      cord blood: 0.103 mumol/L (2.14 micrograms/dL) and 0.0025 mumol/L (0.028
      microgram/dL). The concentration of lead and cadmium in cord blood was 78% and
      33% of the concentration, respectively, in maternal blood. This difference seems
      to reflect the activity of the placental barrier which apparently is more
      effective in the case of cadmium. Contrary to this pattern, hair levels of both
      metals were lower in mothers (Pb 0.004 mumol = 0.86 microgram/g dry mass, Cd
      0.0012 mumol = 0.13 microgram/g dry mass) than in newborns (Pb 0.02 mumol = 5.07
      micrograms/g dry mass, Cd 0.002 mumol = 0.22 microgram/g dry mass). These
      findings indicate that accumulation of lead and cadmium begins in fetal life. A
      statistically significant correlation was revealed between maternal venous and
      umbilical cord blood levels of lead (r = 0.59, p = 0.000001) and cadmium (r =
      0.23, p = 0.04). The levels of both metals seemed to be without effect on the
      health status and body dimensions measured. Significantly higher levels of
      cadmium were detected in women who reported a history of abortions.
      Concentrations of lead and cadmium in blood or hair were not related to
      education, employment during pregnancy, past infectious diseases, number of
      pregnancies, or dwelling conditions.

PMID- 12514902
TI  - [Long-term and late results of treatment in patients with a history of testicular
      torsion].
AB  - Testicular torsion is a surgical urgency. It may lead to loss of that organ and
      moreover, as revealed by experimental studies and clinical findings in adults,
      induces autoimmunological reactions with subsequent male infertility. To
      elucidate these sequellae the following questions seem to be relevant 1. Are
      there any antisperm antibodies or shifts in T cell CD4+, CD8+ and NK
      subpopulations in boys with a history of testicular torsion? 2. Is production of
      antisperm antibodies initiated and maintained in childhood, and amplified after
      puberty? 3. Does the age at testicular torsion and duration of exposure to sperm
      antigens/testicular tissue have an effect on induction and levels of antisperm
      antibodies? 4. Is hormonal function of testis/testes and gonadotropic activity of
      the pituitary gland normal in these patients? 5. What conditions (duration,
      subjective and objective symptoms) are associated with testicular torsion; what
      kind of intraoperative findings can be expected; what is the influence of
      testicular torsion on the twisted testis? The study group (GB) consisted of 37
      boys and men aged from 8 months to 27 years (mean 12.3 years) recruited from 86
      patients seen for testicular torsion at the Department of Pediatric Surgery,
      Pomeranian Academy of Medicine in Szczecin, between 1967 and 1992. The control
      group (GK) comprised 42 healthy boys and men aged 3 to 33 years (mean 12.1 years)
      (Tab. 1). The analysis was based on: 1) clinical files; 2) follow-up results; 3)
      laboratory findings; 4) statistics. According to clinical data and physical
      examination, testicular torsion usually appeared during puberty, neonatal period
      and infancy and the mean duration of torsion was 12.4 days. The best prognosis
      for salvage of the twisted testis was for torsions lasting no longer than 8
      hours. Only 8 of 37 twisted testes could be salvaged (including 4 hypotrophic
      testes; Tab. 2). There were 21 positive ELISA tests (level of antisperm
      antibodies exceeding 2 fg/pl) in the study group (mean 4.45 +/- 5.6 fg/pl),
      including 13 boys with testicular torsion in the prepubertal age and 8 during
      puberty (Tab. 3). A tendency to higher levels of antibodies with age was
      observed. In the control group there were 35 negative and 7 positive results
      (mean 1.05 +/- 1.86 fg/pl) (Tab. 4), significantly less than in the study group
      (p < 0.001). Trend curves (Fig. 1) and Pearson's correlation coefficients (Fig.
      2) for levels of antibodies and age at presentation of testicular torsion were
      established for both groups. Mean percentages of CD4+, CD8+ and NK cells
      (indirect immunofluorescence test with monoclonal antibodies) were
      insignificantly lower in the study group (Fig. 3). Shifts in favor of CD4+ and NK
      subpopulations found in some patients correlated with high levels of antisperm
      antibodies (Tab. 5 and Fig. 4). Elevated LH and/or FSH (21 patients) and/or
      testosterone levels (13 patients) were usually observed during puberty (Tab. 6).
      The results indicate that antisperm antibodies are detected in more than half of
      the boys with a history of testicular torsion. This is accompanied in some cases
      by shifts in CD4+ and NK lymphocyte subpopulations correlating with high antibody
      levels. Production of antisperm antibodies initiated during prepuberty (in
      infancy or even in the neonatal period) persists and is amplified after puberty
      due to increasing amounts of antigen material. Age at testicular torsion (age at
      potential exposure to spermatic antigens/testicular tissue from the twisted or de
      twisted testis with severe haemorrhagic lesions or left in the abdominal cavity)
      has an effect on the future production and levels of antisperm antibodies.
      Disturbances in the secretion of LH and/or FSH were observed in 2/3 of the
      boys/men with a history of testicular torsion. Abnormal secretion of testosterone
      was found in 1/3 of the patients. These hormonal disorders seem to have no
      influence on virilization, libido or sexual potency.

PMID- 12514903
TI  - [Renal scintigraphy using technetium Tc 99m-ethylenedicysteine or SPECT as a
      method for examining kidneys in children diagnosed with vesicoureteral reflux].
AB  - Vesicoureteral reflux (VUR) can lead to parenchymal lesions of the kidneys. Renal
      scarring is an important cause of chronic renal failure and hypertension in
      children. Effective prevention necessitates an early diagnosis of urinary tract
      pathology. The aim of this work was to examine renal morphology and function in
      VUR using radioisotope techniques and to compare the sensitivity of the planar
      technique and single photon emission computed tomography (SPECT) for detection of
      renal scarring. The following examinations were performed in 45 children with
      VUR: ultrasonography, renoscintigraphy with technetium-99m-etylenedicysteine (EC
      Tc-99m) or technetium-99m-dimercaptosuccinic acid (DMSA-Tc-99m) in planar and
      SPECT modes. The stage of VUR correlated with cortical lesions as reflected by
      effective renal plasma flow (ERPF), and scarring as shown by static scintigraphy.
      The use of SPECT increased diagnostic sensitivity in the case of small and
      isolated scars. Thus, SPECT would be recommended in children at risk of renal
      scarring. The correlation between ERPF and DMSA scintigraphy findings supports
      the use of EC-Tc-99m renoscintigraphy to monitor the process of renal scarring.

PMID- 12514904
TI  - [Use of hysteroscopy, ultrasonography and selected hormonal tests for diagnosis
      of hyperplastic endometrial changes].
AB  - THE PURPOSE OF THE STUDY: 1. Diagnostic value of ultrasonic endometrium thickness
      measurement and estimation of ultrasonic endometrium qualitative features in
      detecting of pathological changes at women in perimenopausal period. 2.
      Estimation of comparative estrogens and testosterone level in diagnostic of
      endometrial changes at women in postmenopausal period. 3. Qualification
      usefulness of analysis of macroscopic hysteroscopy uterine cavity image in
      detecting of pathological changes at women in perimenopausal period. 4.
      Comparative analysis of fractional curettage and hysteroscopy as a method of
      receiving material from uterus to histological estimation at women in
      perimenopausal period. Material to investigations consist of 242 patients in age
      40-86 years, which were divided into groups in dependence from obtained diagnosis
      on the ground histological estimation sampling received from uterus (BZ--"without
      changes", M--submucosus myomas, P--endometrial polyps, H--endometrial
      hyperplasia, CA--endometrial carcinoma). In all of women transvaginal ultrasonic
      estimation of endometrium (TVS) and fractional curettage were executed. In 160
      from them also hysteroscopy with endometrial biopsy was performed. In 53 women in
      postmenopausal period not using of hormonal replacement therapy one marked
      concentration estron (E1), estradiol (E2) and testosterone (T) in serum of blood.
      TVS were performed using a transducer with an emission frequency of 7.0 MHz (B &
      K Medical 3535). Serum concentration of testosterone and estradiol were executed
      with EIA assay, however concentration of estron with RIA assays. To endoscopic
      investigations diagnostic and operative hysteroscops and resectoscope were used.
      Average thickness of endometrium in group CA, H and P (properly 8.96 and 6.09 and
      5.02 mm) showed essential differences in comparison with group BZ (3.38 mm, Tab.
      1). In group CA and H greatest cumulation of abnormal features of TVS image
      (endometrial thickness > 2.5 mm, hyperechoic, heterogeneous and containing cystic
      spaces endometrium, deformation of middle echo, indistinctness of endo-myometrial
      border, presence of focal changes in structure of endometrium and presence of
      fluid in uterine cavity > 1 cm3) was ascertained (Tab. 2, 3, 4). Hysteroscopic
      macroscopic image showed conformity with histological estimation in groups BZ, M,
      P, H and CA properly in 78.35, 93.75, 88.33, 22.22 and 88.33% (Tab. 7). On base
      of histological estimation 159 (65.7% of chances) of pathological changes (P-68,
      CA-37, M-32, H-22 chances) were detected (Tab. 8). Among them were 41 of
      asymptomatic chances (P-24, M-7, H-6, CA-4 chances). In hysteroscopy, all but one
      chance of pathological changes were detected, however curettage skipped most of
      focal changes. CONCLUSIONS: 1. Ultrasonic measurement of endometrial thickness is
      sensitive index in detecting cancer and pathological endometrial hyperplasia,
      instead possesses smaller value in detecting of endometrial polyps and
      endometrial myomas. 2. Connection of measurement of endometrial thickness with
      estimation of qualitative features of endometrial and uterine cavity TVS image
      improves results of detecting all of types intrauterine pathology. 3. Dependence
      between estrogens level and with thickness of endometrium was confirmed.
      Practical value of hormonal estimations in diagnostics of endometrial
      pathological changes is however not large. 4. Analysis of hysteroscopic picture
      is characterised high agreement with histological investigation with reference to
      endometrial cancer, endometrial polyps and submucosus myomas. 5. Hysteroskopy
      with direct biopsy possesses superiority over curettage in detecting all of types
      of intrauterine pathology, in particular focal changes. 6. Hysteroscopy should
      determine method of choice at women with recurrent bleedings from uterus, which
      with curettage pathological changes did not detect.

PMID- 12514905
TI  - [Improved method for delivery room collection and storage of human cord blood
      cells for grafting].
AB  - Haematopoietic stem cell transplantation is indicated in several haematologic and
      genetic diseases, the most notable being aplastic anemia and leukemias. Bone
      marrow has been the traditional source of these cells. Human umbilical cord blood
      (UCB) has recently become an alternative source of haematopoietic stem cells for
      transplants. The advantages of cord blood include noninvasive collection without
      risk to mother and neonate, low risk of viral infection, and immunologic
      immaturity of cord cells. Single umbilical cord blood donation is usually
      sufficient for transplantation to adult recipients. Additionally, banking of HLA
      typed UCB appears valuable in patients lacking a family donor. This study has
      focused on basic "perinatological" parameters of umbilical cord blood: average
      volume of single donation UCB and initial storage conditions before isolation of
      haematopoietic stem cells. Additionally, the mean content of CD34+ haematopoietic
      stem cells in leukocyte, lymphocyte and mononuclear cell fractions was
      established. Correlations between levels of so-called pro-inflammatory cytokines
      (present in cord blood serum) and number, viability and clonogenicity of cord
      blood mononuclear cells were checked. UCB samples were obtained by "open"
      collection during vaginal deliveries and cesarean sections. The collected blood
      was stored in solutions of anticoagulants (ACD, CPDA-1, heparin) and culture
      media (PBS, Iscove medium, RPMI), during several time intervals (0-1 h, 1-6 h, 6
      12 h, 12-24 h) and at two temperatures (+4 degrees C, ambient). UCB volumes, as
      well as MNC counts, correlated with delivery type, placental weight, neonatal
      body weight and duration of pregnancy. The concentration, viability and
      clonogenicity of MNCs were assessed after collection and storage. The
      subpopulation of CD34+ haematopoietic stem cells was isolated from MNCs using
      monoclonal antibodies and magnetic-based separation. The number, viability and
      clonogenicity of CD34+ cells were evaluated. Subsequently in some samples, the
      concentration of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8,
      and TNF-alpha), number of mononuclear cells and in vitro clonogenicity of myeloid
      progenitors (CFU-GM) were determined. It was found that the collected blood
      volume depended on neonatal body weight (Fig. 1). Umbilical blood could be stored
      either at ambient temperature (Fig. 4) or +4 degrees C (recommended because of
      reduced risk of infection) for up to 24 hours in RPMI solution (Fig. 5) with
      heparin (Fig. 2, 3). CD34+ cell count correlated with mononuclear cell count only
      (Fig. 6). A negative correlation between the number of mononuclear cells and
      concentration of TNF-alpha was revealed (Fig. 7), as well as between the number
      of detectable CFU-GM and concentration of IL-1 beta (Fig. 8). In conclusion, UCB
      collection and short-term storage is a safe and simple method for graftable
      haematopoietic stem cell recovery. Save for IL-1 beta and TNF-alpha, cytokine
      levels did not correlate with the studied parameters of umbilical cord blood.

PMID- 12514906
TI  - [Analysis of selected environmental and biophysical parameters during menarche].
AB  - It is challenging at the end of the 20th century to verify our concept of the
      secular trend in pubertal development, its pace, and role of environmental
      factors in the process. The study group consisted of patients visiting the
      Pediatric Gynecology Center in Szczecin, Poland. Retrospective analysis was based
      on 4386 cases recorded between 1975 and 1997. Participating in the prospective
      part of the study were 111 patients seen at the Center between 1994 and 1997
      during the first 6 months after their first menstruation. The prospective group
      was divided into two groups according to gynecologic age: (1) up to three months
      and (2) between three and six months after menarche. The retrospective analysis
      was based on age, date of menarche, permanent residence (large town, small town,
      village), mother's menarcheal age, parents' education level and family status. In
      the prospective study, history was taken and the patients underwent standard
      physical examination. Additionally, school performance and number of siblings
      were recorded. The following parameters were studied: body mass, BMI, height,
      tertiary sex features. Ultrasonographic examinations were done with a 3.5 MHz
      transabdominal probe. Hormonal tests included blood concentrations of FSH, LH, E2
      and PRL (basal and Metoclopramid-induced). Several correlations were studied,
      including menarcheal age and permanent residence, mother's and daughter's age at
      menarche, menarcheal age and parents' education, school performance, and family
      status. One standard deviation was taken as cut-off value for overweight and
      underweight groups. The maturity of tertiary sex features at the time of first
      menstruation was examined. Ultrasound was used to determine primary and secondary
      sex features. The study disclosed that menarche occurs most frequently in January
      and July (Table 1). A decline in the pace of pubertal development and narrowing
      of the urban-rural gap was observed (Tables 2-5). A significant correlation
      between the age at first menstruation in mothers and their daughters was observed
      (Table 6). Late menarche correlated with low level of paternal and especially
      maternal education, incomplete family status and poor school performance (Tables
      7-9). At the time of menarche the mean body mass was 48 kg, mean height 159 cm,
      and tertiary sex features represented fourth, rarely third, stage. During six
      months after first menstrual blooding a significant increase in weight was noted,
      but there was no correlation between overweight and age at first menstruation
      (Tables 10-12). At the time of first menstruation the uterine body was already
      larger than the cervix (Table 13). In patients at the gynecologic age of 3 to 6
      months after menarche there was a significant increase in the prolactin reserve
      (Table 14). CONCLUSIONS: 1. Analysis of the secular trend for the last two
      decades of the 20th century revealed no acceleration in pubertal development of
      girls. A reduction in environmentally-dependent differences in menarcheal age
      (urban vs. rural residence) was observed. 2. Marked influence of the environment
      (family and school factors) on the age at menarche was evidenced. 3. At the age
      of first menstruation, biophysical parameters (height, body mass, sex features,
      concentrations of hormones) revealed specific patterns but subtle individual
      differences remain.

PMID- 12514907
TI  - [Objective evaluation of respiratory function of the larynx after partial
      laryngectomy of various range].
AB  - The aim of the study was to identify factors and their effect on the respiratory
      efficiency of the larynx after partial laryngectomy. The material consisted of 72
      patients aged 30 to 71 years (mean 54.3 years) who underwent partial laryngectomy
      due to cancer, and 10 healthy volunteers aged 22 to 29 years (mean 24.5 years).
      Airflow was measured under normal conditions and upon application of external
      resistance. Methods included history taking and physical examination, spirometry,
      laryngovideoscopy (Lvs), and computed tomography (CT) of the larynx. Some airflow
      parameters were decreased prior to surgery in comparison to predicted values. In
      a majority of patients, surgery had a negative effect on all parameters of
      airflow. Reduction was greater for inspiratory than expiratory parameters.
      Analysis of the shape of flow-volume loops in patients after surgery showed that
      the mixed type prevailed. This is characterized by reduction of the inspiratory
      and expiratory parameters, with greater effect on the inspiratory phase.
      Morphologically, the mixed type corresponds to narrowing of various extent with
      flaccid wall stenosis. The flow-volume shape changed dynamically during the
      healing process of the larynx until normalization was observed. This process was
      independent of the type of surgery but depended on the size of the laryngeal
      lumen and wall stiffness. Significant differences were found when laryngeal lumen
      was measured using CT or Lvs, with Lvs being more accurate. Lung volume
      parameters remained unchanged, but a statistically significant relationship with
      lumen size was observed both in experimental and clinical investigations. The
      most useful parameters for estimating laryngeal airflow were: PIF, FIF50, FIV1,
      FIV1%/N FEV1 and % Rz/N PEF. Upper and lower values were established for PIF (1.4
      2.0 L/s), FIF50 (0.7-1.9 L/s), FIV1 (0.7-1.6 L), FIV1%/N FEV1 (40-60%),% Rz/N PEF
      (20-40%) on the basis of which the decision to restore respiration through the
      larynx (decannulation) may be made. It can be concluded from the results that
      spirometry and Lvs are more accurate than CT for assessment of the respiratory
      function of the larynx after partial laryngectomy.

PMID- 12514908
TI  - [Effect of TFX preparation on the course of pregnancy in rabbits with
      experimental antiphospholipid syndrome].
AB  - Recurrent thrombo-embolic episodes and pregnancy loss, thrombocytopenia and the
      presence of antiphospholipid antibodies, first described in 1983 by Hughes and
      defined by Harris in 1987, are characteristic of the primary antiphospholipid
      syndrome (APS). APS is the cause of obstetrical problems in the form of recurrent
      miscarriages, intrauterine fetal death or growth retardation, and EPH gestosis.
      Clinical symptoms described above are probably mediated by antiphospholipid
      antibodies which interact with endothelial and trophoblastic cells, blood
      platelets, embryonic tissue cells, as well as with coagulation factors and
      proteins involved in the coagulation cascade or in antibody binding. Management
      of APS includes antiaggregation, anticoagulation, immunosuppression, and
      intravenous administration of gamma globulins. Successful treatment is not always
      the case and search for more efficient therapies continues. The importance of
      animal experiments led to the design at the Department of Pathology of Pregnancy
      and Labour of an APS model in pregnant and nonpregnant rabbits. As Turowski et
      al. have confirmed the immunomodulating action of TFX in rabbits, it seemed
      justified to examine the properties of this preparation in pregnant rabbits with
      experimentally induced APS. The material consisted of 30 pregnant New Zealand
      rabbits, divided into the following groups: I--10 pregnant rabbits (and 63
      fetuses) treated intradermally twice weekly since the 10th day of pregnancy with
      cardiolipin together with adjuvant; I-K--5 pregnant rabbits (and 17 fetuses)
      treated with cardiolipin and adjuvant in the same manner as group I and
      additionally with intramuscular injections of 0.9% NaCl on the 20th, 21st, and
      22nd day; I-T--10 pregnant rabbits (and 66 fetuses) treated with cardiolipin with
      adjuvant in the same manner as group I and additionally with intramuscular
      injections of 10 mg/day of TFX (Jelfa, Poland) on the 20th, 21st, and 22nd day of
      pregnancy; K--5 pregnant rabbits (and 27 fetuses) treated with injections of 0.9%
      NaCl twice weekly. Blood samples for laboratory analysis were collected by
      cardiac puncture before immunization (sample I) and on the day of caesarean
      section (sample II). Platelet counts and APTT tests were done. Numbers of live
      and dead newborns, resorbed fetuses, body mass, newborn viability and survival
      rates were recorded. TFX administered to pregnant rabbits with experimentally
      induced antiphospholipid syndrome increased the number of live newborns, reduced
      the incidence of fetal resorption, increased the viability and survival rate of
      newborn rabbits. The beneficial effect of TFX on APTT and platelet count was
      revealed, such that these parameters remained within the normal range despite
      immunization. Morphological changes observed in the placenta were not specific.

PMID- 12514909
TI  - [Effect of group psychotherapy on changes in symptoms and personality traits in
      patients with anxiety syndromes].
AB  - Psychotherapy remains the most efficient form of treatment in neurotic and
      personality disorders. It is a process whereby the therapist can influence and
      change the patient's personality. As a result, patients are able to better
      understand their experiences and behavior and are given a chance to be freed from
      symptoms. The goal of the present study was to establish the relationship between
      group psychotherapy and specific symptom clusters, and to follow changes in the
      personality structure of patients of both genders diagnosed according to ICD-10
      classification. The Symptoms Questionnaire and the Personality Factor test were
      used to determine the severity of symptoms and study personality traits. The
      study group consisted of 115 patients (76 women and 39 men) with neurotic or
      personality disorders, participating in group therapy at the Day Care Unit of the
      Department of Psychiatry, Pomeranian Academy of Medicine in Szczecin between 1992
      and 1998. Four groups were formed depending on the diagnosis according to ICD-10
      classification: anxiety disorders--F41; somatic disorders--F45; neurotic
      disorders--F48; and personality disorders--F60 (Table 1). Treatment started and
      ended with a CV Questionnaire, Symptoms Questionnaire and Personality Factor
      test. Group psychotherapy was in the open form and the duration of treatment was
      12 weeks with 2 sessions per day. In order to detect any improvement in mental
      health and symptoms, patients were given the Symptoms Questionnaire on a weekly
      basis. Statistics were done with the SPSS software package. It was found that the
      global intensity of symptoms before treatment was highest in patients with
      somatic form of the disorder. In this group after therapy, the intensity of
      symptoms was lowest, probably because of conversion of primary to secondary
      anxiety. A considerable decrease in the intensity of symptoms may also be
      explained by stronger motivation of these patients to benefit from therapy
      because of their severe symptoms. A link between the clinical diagnosis according
      to ICD-10 and some symptoms reported by the patients was noted. Thus, the
      Symptoms Questionnaire could be a useful tool precisely revealing specific
      symptoms in some disorders. No statistically significant differences on the
      Symptoms Questionnaire scale based on ICD-10, nor any differences in personality
      traits were found. The personality traits were different for men and women before
      and after therapy. As for hysterical symptoms, improvement was greater in women.
      After psychotherapy, the structure of personality traits improved in both sexes
      (Fig. 1). An essential alleviation of symptoms was found at the beginning and at
      the end of treatment (Table 2). The main conclusions are: 1. Group psychotherapy
      is an efficient method of treatment for patients who suffer from anxiety-related
      disorders. 2. The Symptoms Questionnaire and Personality Factor test were very
      useful for assessing the results of psychotherapy. 3. Alleviation of symptoms
      during treatment differed between men and women in 3 out of 13 symptom clusters
      and no significant differences between disorders according to ICD-10 were found.
      Consequently, these criteria are of little value for preliminary evaluation of
      therapeutic success. 4. Alleviation of symptoms was observed at the beginning and
      end of treatment. Symptom severity remained constant in the middle part of
      treatment.

PMID- 12514910
TI  - [Effect of osteotomy metal plate anastomosis with the femur on stimulation of
      lower femur growth in children].
AB  - The aims of this study were (1) to examine structural, electrostatic and thermal
      changes taking place in the vicinity of a metal plate; (2) to establish factors
      that affect the growth of the operated extremity; (3) to quantify the extent and
      dynamics of growth enhancement depending on retention time of the plate and
      distance of the plate from growth cartilage; and (4) to draw practical
      conclusions. The study consisted of an experimental and a clinical part. The
      experimental part was done in 45 children aged 2 to 14 years and included
      histology of tissues sampled from the vicinity of bone fixation, examination with
      a thermographic camera of temperature distribution around the operated hip
      joints, and measurements of the electric potential between the plate stabilizer
      and femur. In the clinical part, an orthopedic examination was performed in 100
      children treated surgically between 1990 and 1993 at the Department of Pediatric
      Orthopedics of the Pomeranian Academy of Medicine. In order to reveal any
      differences in limb length and to verify the measurements done with a tape, AP
      radiograms of femoral bones with both epiphyses were obtained. The following
      conclusions were drawn from the results: (1) In the vicinity of the metal plate,
      processes of remodeling and destruction take place, most evident in the area of
      contact between the plate and bone; (2) Brown amorphous deposits of iron were
      present in all samples from the vicinity of bone fixation; (3) Temperatures near
      the operated joint were highest during the first six months after surgery and
      gradually decreased thereafter; (4) The electric potential between the plate and
      bone increased with time, but this did not enhance growth of the operated
      extremity; (5) Placement of the horizontal arm of the plate near the growth
      cartilage of the femoral head enhanced growth of the operated extremity; (6)
      Enhancement of growth was greatest in children operated between 2 and 10 years of
      age and growth was distinguished by regular increase in length during the first
      12 months from surgery; (7) Fixation of the osteotomy of the proximal femur in
      children may be one of the causes of enhancement of growth of the operated
      extremity. Early removal of the fixation device after healing of the osteotomy
      may arrest further growth of the extremity; (8) Coexistence of Ehlers-Danlos
      syndrome does not essentially influence enhancement of growth of the operated
      extremity.

PMID- 12514911
TI  - [Usefulness of uroflowmetry for postoperative monitoring of boys with
      hypospadia].
AB  - Uroflowmetry is a non-invasive diagnostic method well accepted by children and
      uninfluenced by stress. It allows the study of natural urination and could
      significantly reduce the frequency of calibration and postoperative urethral
      dilation (invasive, poorly tolerated procedures) in hypospadias. However, the
      usefulness of uroflowmetry in children has been questioned. The aim of this study
      was: (1) to assess the repeatability of uroflowmetry and the
      objectiveness/reliability of the procedure in children; (2) to check whether
      uroflowmetry could replace urethral calibration for postoperative monitoring of
      patients with hypospadia. Preoperative and postoperative uroflowmetric
      investigations and urethral calibrations were performed in 54 boys aged 5-14
      years (Table 1) forming the study group (GB) (360 uroflowmetric measurements in
      total). The results were compared with uroflowmetry results in 26 boys of the
      same age from the control group (GK) (102 measurements in total). To measure the
      rate at which urine passes through the urethra, the author constructed a simple
      apparatus (basing on the apparatus for adult patients used by Janosz) (Fig. 1).
      For urethral calibration, metal bougies manufactured by PennTM were used.
      Documentation consisted of data sheets which were next computer processed (Fig.
      2). The preoperative and postoperative results of uroflowmetry (voiding time,
      total volume voided, average flow rate, maximal flow rate, voiding time for first
      100 mL of urine, average flow rate during first 10 s) were compared for each
      patient. Next, the results in the study group were compared with age-matched
      controls (Tables 2-5, Fig. 3) and with urethral calibration values (Table 6; Fig.
      9). 462 urination curves (360 from the studied group and 102 from the control
      group) were examined and 6 curve shapes were recognized (Fig. 4). Graphical
      analysis of individual urination curves in the study and control groups was done
      to evaluate the repeatability of the method (Fig. 5). Statistical and graphical
      analysis of 4 uroflowmetric parameters (average flow, maximal flow, voiding time
      for first 100 mL of urine, average flow rate during first 10 s) were compared
      with mean values and standard deviation in the age subgroups of the study and
      control groups (Fig. 6) and with urethral calibration values in the study group
      (Fig. 7). Correlation between maximal flow rate and urethral calibration after
      surgery was checked (Fig. 8). Maximal flow rate correlated with the corresponding
      urethral calibration value (Table 6; Fig. 9). The homogenous clinical material
      (boys with hypospadias) allowed the evaluation of the uroflowmeter as to
      precision and repeatability. The apparatus proved reliable and facilitated the
      preoperative evaluation and postoperative monitoring in hypospadias. The
      following conclusions were drawn: (1) Uroflowmetry is an objective, reliable and
      repeatable investigation in children; (2) Uroflowmetry could replace urethral
      calibration for postoperative monitoring of hypospadia patients.

PMID- 12514912
TI  - [Bibliography of scientific publications of the Pomeranian Academy of Medicine in
      Szczecin for 1999].

PMID- 12514913
TI  - Gambling participation in the U.S.--results from a national survey.
AB  - Demographic patterns of gambling participation in the U.S. were examined. A
      national telephone survey was conducted with 2,630 representative U.S. residents
      aged 18 or older. The sample as weighted for analysis was 48% male, 12% black,
      and 11% Hispanic. Respondents were questioned on 15 types of gambling: how often
      they played and how much they won or lost. Eighty-two percent gambled in the past
      year. Lottery was the most commonly played game, while casino gambling accounted
      for the largest extent of gambling involvement. Men and women were equally likely
      to gamble in the past year, but men gambled more frequently and had larger wins
      and losses, particularly on sports betting and games of skill. Blacks were less
      likely to have gambled in the past year, but blacks who gambled did so more
      heavily than other racial groups. Blacks and Hispanics were more likely than
      average to be pathological gamblers. The rate of past year gambling declined with
      age, but extent of gambling involvement among gamblers did not vary with age.
      Rates of participation in most forms of gambling increased with socioeconomic
      status, but higher socioeconomic status gamblers had lower rates of pathological
      gambling, and lower extent of gambling involvement, particularly for lottery. New
      Englanders gambled more heavily than other Americans. Comparison with past
      studies showed an increase in overall gambling participation in the U.S., and
      large increases in rates of participation in lottery and casino gambling.

PMID- 12514914
TI  - Measuring gambling outcomes among college students.
AB  - The present research describes the proposal and validation of three gambling
      outcome measures, the Gambling Quantity and Perceived Norms Scale (GQPN), the
      Gambling Problem Index (GPI), and the Gambling Readiness to Change Questionnaire
      (GRTC). The study consisted of 560 undergraduate college students who completed a
      survey including the newly constructed measures and other measures designed to
      assess convergent validity. Results confirmed good reliability and convergent
      validity of all three measures. Implications for evaluating efficacy of treatment
      and prevention interventions are detailed.

PMID- 12514915
TI  - Exploring college student gambling motivation.
AB  - The present research combined qualitative and quantitative approaches in
      examining gambling motives among college student gamblers. A comprehensive set of
      16 gambling motives was identified by categorizing 762 open-ended reasons for
      gambling, provided by 184 college student gamblers. Results revealed that most
      college students gamble to win money, for fun, for social reasons, for
      excitement, or just to have something to do. Overall, the results suggest the
      need for an eclectic biopsychosocial approach with regard to etiology of college
      student gambling.

PMID- 12514916
TI  - Modelling the economics of gaming in South Africa.
AB  - This paper considers the application of two models for determining the optimal
      location and characteristics of a casino in a post-apartheid South Africa. The
      intention in developing the models was to allow provinces a facility for
      considering how to maximize the return to the stakeholders in the license award
      process, namely society at large, as represented by the provincial government,
      and the casino operator. The Allocation Model works on an estimate of total
      potential gambling spend and how that may be best distributed amongst a number of
      casinos. The Profitability model takes the estimated gaming spend from the
      allocation model and assesses the appropriate size and characteristics of the
      casino best suited to this level of gaming spend. It can then simulate levels of
      profitability for different proposed sizes and characteristics of proposed
      casinos. Together these models represent a powerful assessment mechanism for a
      country considering the introduction or radical changing of gaming legislation.

PMID- 12514917
TI  - [The fluorine problem in Belgium: another food scare in Europe?].

PMID- 12514918
TI  - Taurine: a conditionally essential amino acid in humans? An overview in health
      and disease.
AB  - Taurine, a sulphur containing amino acid, is the most abundant intracellular
      amino acid in humans, and is implicated in numerous biological and physiological
      functions. This comprehensive overview explores areas, from its characterisation
      to its potential clinical benefit as a conditionally essential amino acid and a
      pharmaconutrient. In healthy individuals the diet is the usual source of taurine;
      although in the presence of vitamin B6 it is also synthesised from methionine and
      cysteine. Taurine has a unique chemical structure that implies important
      physiological functions: bile acid conjugation and cholestasis prevention,
      antiarrhythmic/inotropic/chronotropic effects, central nervous system
      neuromodulation, retinal development and function, endocrine/metabolic effects
      and antioxidant/antiinflammatory properties. Taurine is an essential amino acid
      for preterm neonates and is assured by breast milk. Specific groups of
      individuals are at risk for taurine deficiency and may benefit from
      supplementation, e.g. patients requiring long-term parenteral nutrition
      (including premature and newborn infants); those with chronic hepatic, heart or
      renal failure. Further studies are required to determine the benefits of
      replenishing taurine pools as well as the need to include taurine routinely in
      parenteral nutrition regimens.

PMID- 12514919
TI  - [Flavonoids: properties and anti-oxidizing action].
AB  - Flavonoids are phenolic compounds that represent substantial constituents of the
      non-energetic part of the human diet. They are naturally found in vegetables,
      berries, fruits, wine and beer. There are more than 5000 different flavonoids.
      The average intake depend on the country but the average intake is approximately
      23 mg/day; quercetin is predominant at 16 mg/day. Flavonoids were considered
      initially to be substances without any benefit for humans. Later, it has been
      reported that they exert multiple biological effects due to their antioxidant and
      free radical-scavenging abilities. Although results from different studies have
      demonstrated that flavonoids can act as pro-oxidant at very high doses, most
      investigations have reported anti-inflammatory, antiviral, or anti-allergic
      effects and a protective role in heart diseases, cancer and different
      pathologies.

PMID- 12514920
TI  - [Ethical and clinical decisions on artificial hydration and feeding via tube in
      the terminally ill].
AB  - Tube feeding is a widely used medical treatment for providing nutrition to
      terminally ill patients. Long term nutritional support in these patients or
      patients with irreversible neurological deterioration create a host of ethical
      and legal conflicts with difficult solutions. This work looks at the cultural and
      ethical-legal basis of these decisions and gives simple suggestions that might
      help the health care provider in making a viable clinical decision. However, each
      case should be treated in an individualized manner taking into consideration the
      rights and desires of each patient and their families.

PMID- 12514921
TI  - [Relation among micronutrient intakes with CD4 count in HIV infected patients].
AB  - INTRODUCTION: The impact of micronutrients on HIV disease progression has been an
      area of great interest. Several studies have shown an association between disease
      progression and micronutrient status. The aim of our study was to assess the
      correlation between micronutrients intakes and immune status in HIV infected
      patients. MATERIAL AND METHODS: A total of 119 patients were evaluated. Nobody
      dropped out. In all patients the following parameters were assessed; age, sex,
      treatment with anti-retroviral drugs, performed an anthropometric evaluation
      (weight, tricipital skinfold, midarm circumference, and body mass index (BMI))
      and a biochemical evaluation (glucose, albumin, prealbumin, transferrin, total
      proteins, limphocytes and count of CD4). All patients received instruction in 24
      hour written food record keeping. RESULTS: Patients had an average age 37.9 +/-
      9.9 years, weight 64.5 +/- 13.2 kg and body mass index 22.5 +/- 3.5. Levels of
      total proteins, albumin, prealbumin y transferrin were normal. Percentile
      distribution of anthropometric parameters showed a deep depletion in muscular
      protein compartiment, 53.1% of patients had tricipital skinfold under P 50, 91.8%
      had midarm muscle circumference under P 50. The correlation analysis among
      dietary intake and immune status, showed a positive association among vitamin A
      intake and vitamin D with CD4+ (r = 0.35; p < 0.01) and (r = 0.51; p < 0.001),
      respectively. In the multivariant analysis with dependent variable (CD4 count),
      only vitamin D remained in the model (F = 16.99; p < 0.001), with an increase of
      34 (CI 95%: 5.81-167.3) CD4+ (count/uL) with each microgram of vitamin D intake,
      adjusted by age, sex, energy and protein intake, and anti-retroviral drugs.
      CONCLUSION: Vitamin A, and D intakes were correlated with CD4 count, only vitamin
      D remained as a independent predictor parameter in a in multivariant model.

PMID- 12514922
TI  - [Anthropometric assessment and vitamin intake by a group of elderly
      institucionalized individuals in the province of Leon (Spain)].
AB  - INTRODUCTION: Nutritional deficiencies of micronutrients in elderly people are
      frequent, and therefore this constitutes a main aspect in the maintenance and the
      restoration of health and well-being. AIM: The anthropometric assessment of a
      population of elderly people and the estimation of the dietetic intake of
      vitamins. MATERIAL AND METHODS: The sample of the survey was composed of 124
      elderly persons (60 males and 64 females), aged between 65 and 98, who were
      living in five institutions for old people in the province of Leon. An
      anthropometric assessment was made as well as a record of food intake throughout
      7 days determined by "the precise weighting method". The contents in vitamin were
      calculated from the Spanish Food Composition Tables and they were compared to the
      dietetic recommendations for Spanish population older than 65 years old. RESULTS:
      The Body Mass Index (BMI) was similar in men (27.5 +/- 4.2 kg/m2) and in women
      (28.1 +/- 5.9 kg/m2) with no significant differences between them, although there
      is a high prevalence of obesity (BMI > 30 kg/m2) in the studied population, both
      in females (41%) and in males (28%). Regarding the vitamin intake, the mean
      dietetic content of thiamine, niacin and vitamin C supplies the 100% of the
      recommended intake of the population in study in both sexes. However, in the case
      of folic acid, vitamin A, riboflavin and vitamin B12, despite the mean intake
      supplies the recommendations, there are important percentages of population who
      have an inadequate intake. As regards the rest of the vitamins (vitamin B6,
      vitamin D and vitamin E), the situation in very unsuitable because almost the
      whole sample shows lower amount of intakes than the recommended values (93.5% vs
      67.8% for vitamin B6, 84.5% vs 84.6% for vitamin D, and 88.3% vs 92.2% for
      vitamin E, for men and women, respectively).

PMID- 12514923
TI  - [Dietary assessment program evaluation (third-year secondary school students)].
AB  - ANTECEDENTS: The appropriate contribution of nutrients determines the phenotypic
      expression of the genotype. OBJECTIVE: The Dietary Assessment Program consists on
      the transmission of necessary information to carry out a balanced diet. AMBIT:
      The program embraces twenty-three schools in the Basque Country, on a total of
      2,400 girls and boys, studying 3rd year of ESO. SUBJECTS: The evaluation was
      carried out on 130 girls and boys at Liceo Santo Tomas in Donostia. The DAP
      consists of an educational program with the students (theoretical and practical
      workshop), educational program for parents and educators and evaluation program
      of the Dietary Intervention. RESULTS: The students' response was positive. The
      parents and educators maintained the same constructive attitude, in all the
      projects. EVALUATION: 61% of the teenagers said that their diet stays equally
      (28% previous balanced diet), 2% worse and 36% find an improvement (3% great
      improvement). In 94% of those interviewed there is a theoretical-subjective
      agreement in the answer. 85% of the teenagers are able to identify the
      Mediterranean balanced diet correctly. CONCLUSIONS: 36% of the youths said that
      the quality of their diet has improved. 85% knows the balanced dietary pattern.
      These results encourage us to continue working in the DAP, perfecting and
      modernizing it. A good diet facilitates a good genetic expression and, therefore
      an appropriate nutrition determines the quantity and quality of life. Teenagers
      don't take a balanced diet. A better nutritional education would improve the
      health of future generations.

PMID- 12514924
TI  - Chips for proteomics: a new tool or just hype?

PMID- 12514925
TI  - Antibody microarrays: promises and problems.
AB  - Antibody microarrays have enormous potential for becoming a tool that will allow,
      at the protein level, the type of global characterization of molecular mixtures
      that DNA microarrays already make possible at the RNA and DNA level. However, the
      much higher complexity of proteins both in terms of their sheer number and their
      structural and biochemical diversity necessitates an even more sophisticated
      analysis process. Its eventual realization will be demanding to achieve and
      requires further developments on many technical aspects, not in the least because
      the understanding of proteins is still comparatively less comprehensive than that
      of nucleic acids prior to the emergence of array technologies.

PMID- 12514926
TI  - Protein microarrays: from serodiagnosis to whole proteome scale analysis of the
      immune response against pathogenic microorganisms.
AB  - Microbial diseases remain the most common cause of global mortality and
      morbidity. Scientific and technical achievements have dramatically improved the
      possibilities of investigating the humoral immune response against the whole
      proteome of microbial organisms. A number of genomes of microbial organisms
      responsible for diseases of worldwide medical importance such as Plasmodium,
      Toxoplasma, Mycobacterium, Streptococcus, Neisseria, Salmonella, Borrelia, and
      Rickettsia species have already been sequenced or will be available in the very
      near future. High-throughput assays such as protein microarrays have been
      clinically validated in serum for detecting the presence of antibodies directed
      against microbial antigens. Computational technologies for processing large sets
      of data are rapidly being developed. Such a powerful combination of genomic
      information and assays now offers the opportunity to identify the microbial
      antigens that, either alone or in combination, function as targets of natural
      acquired immunity against infectious diseases. This information will prove
      invaluable for developing vaccines against a series of microorganisms of medical
      relevance that are urgently needed, e.g., malaria. Additional applications of
      these technologies include the development of a microbial antigen array for the
      early serodiagnosis of both common and rare infectious diseases. This review will
      focus on technical and scientific issues concerning the use of antigen
      microarrays for vaccine development and the serodiagnosis of infectious diseases.

PMID- 12514927
TI  - Automated screening procedure for high-throughput generation of antibody
      fragments.
AB  - In the emerging field of proteomics, there is an urgent need for catcher
      molecules such as antibodies for detecting the proteome or parts of the proteome
      in a microarray format. A suitable source for providing a large diversity of
      binders is obtained by combinatorial libraries, such as phage display libraries
      of single chain antibody fragments (scFv) or Fab fragments. To find novel binders
      from the n-CoDeR libraries with a high throughput, we have automated the
      screening process with robotics. The automated system is configured to screen
      tens of thousands of clones per day to target antigens in various formats,
      including peptides and soluble proteins, as well as cell-bound targets; thus, it
      is well designed to meet demands from the proteomics area.

PMID- 12514928
TI  - Single framework recombinant antibody fragments designed for protein chip
      applications.
AB  - High-throughput proteomics, based on the microarray platform, requires stable,
      highly functional components that will yield a highly sensitive read-out of low
      abundance proteins. Although antibodies are the best characterized binding
      molecules for this purpose, only a fraction of them appear to behave
      satisfactorily in the chip format. Therefore, high demands need to be placed on
      their molecular design. In the present study, we have focused on recombinant
      antibody design based on a single framework for protein chip applications, aiming
      at defining crucial molecular probe parameters. Our results show that engineered
      human recombinant scFv antibody fragments that displayed appropriate biophysical
      properties (molecular [functional] stability in particular) can be generated,
      making them prime candidates for high-density antibody arrays. In fact, a
      superior framework that displays both multifaceted adsorption properties and very
      high functional stability over several months on chips (stored in a dried-out
      state) was identified. Taken together, designed scFv fragments based on a single
      molecular scaffold, readily accessible in large phage display libraries, can
      undoubtedly meet the requirements of probe content in antibody microarrays,
      particularly for global proteome analysis.

PMID- 12514929
TI  - Using protein microarrays to study cancer.
AB  - Microarrays or "biochips" provide an efficient way to achieve a global molecular
      perspective of human disease. DNA microarrays have been used extensively to
      generate transcriptional fingerprints of cancer. More recently, high-throughput
      technique to study proteins have also been developed. Biochip-based microarrays
      containing spotted antigens or antibodies offer the ability to study protein
      protein interactions, identify biomarkers, and study the humoral response to
      cancer. This review will focus on developments in the area of antigen and
      antibody microarrays and describe some of their applications to cancer research.

PMID- 12514930
TI  - Cell microarrays: an emerging technology for the characterization of antibodies.
AB  - The possibility to miniaturize and parallelize biological assays has a great
      impact on the development of biomedical technologies. Here, we describe a simple,
      miniaturized, and parallelized method employing entire cells from different cell
      lines displaying a protein of interest on their surface, which were immobilized
      on a microarray slide. Antibodies were added to these cellular microarrays, and
      their specific binding to the cell surface proteins was monitored using
      appropriate fluorescently labeled detection molecules. This new method is
      applicable for rapidly screening cell surface-specific antibodies with respect to
      selectivity and cross-reactivity.

PMID- 12514931
TI  - Membrane biochips.
AB  - Membrane-bound proteins represent the single most important class of drug
      targets. This article discusses the issues surrounding fabrication of membrane
      protein microarrays by conventional robotic pin printing techniques. Ligand
      binding selectivity and specificity to G protein-coupled receptor (GPCR)
      microarrays are presented. The potential applications of these arrays for drug
      screening are discussed.

PMID- 12514932
TI  - Protein and peptide array analysis of autoimmune disease.
AB  - Molecular cloning, sequencing of the human genome, and other major advances in
      biomedical research have contributed substantially to our understanding of
      autoimmune disease. Nevertheless, to date, such advances have failed to reveal
      the etiology of or yield curative therapies for autoimmune disease. New
      approaches are needed. Proteomics, the large-scale study of expression and
      function of proteins that compose our tissues and mediate disease, represents a
      powerful and promising strategy. We developed protein and peptide arrays to
      profile autoantibody responses in autoimmune disease. Protein and peptide array
      analysis of autoimmune samples is revealing human and pathogen proteins involved
      in initiation and perpetuation of autoimmunity. Proteomic determination of
      autoantibody profiles can be utilized for diagnosis, prognostication, and guiding
      tolerizing therapy for autoimmune disease.

PMID- 12514933
TI  - Products for protein analysis.

PMID- 12514934
TI  - Through a glass darkly: complex modulation of common metabolic faults.

PMID- 12514935
TI  - Loci for CETP, LPL, LIPC, and APOC3 affect plasma lipoprotein size and sub
      population distribution in Hispanic and non-Hispanic white subjects: the Columbia
      University BioMarkers Study.
AB  - BACKGROUND AND AIM: The effect of genetic variation on plasma lipoproteins and
      their subfraction distribution was examined. METHODS AND RESULTS: Forty Hispanic
      men and 223 women and 42 non-Hispanic white men and 53 women participated in the
      study. Genotypes for cholesteryl ester transfer protein (CETP TaqIB), hepatic
      lipase (LIPC -480 C > T), lipoprotein lipase (LPL S447X), and apolipoprotein CIII
      (APOC3--455T > C) were determined by polymerase chain reaction. Lipoprotein
      particle size distribution was determined by nuclear magnetic resonance. For all
      but APOC3, genotype effects were homogeneous in the ethnic/racial groups and men
      and women. Effects were seen primarily in the women. Compared to women carriers
      of the common CETP B1 allele, B2B2 women had significantly higher plasma levels
      of high-density lipoprotein cholesterol (HDL-C) (16.4.0%, p = 0.001), reflected
      in the level of larger HDL particles (21.9%, p = 0.001), and larger mean particle
      size of HDL (2.3%, p = 0.01) and low-density lipoproteins (LDL) (1.3%, p = 0.02).
      Compared to LPL 447S homozygous women carriers of the LPL 447X allele had
      significantly lower levels of very-low-density lipoprotein-triglyceride (VLDL-TG)
      (21.0%, p = 0.02). For APOC3, there was significant gender:genotype interaction
      with the genotype differences seen only in the men. Compared to men homozygous
      for the -455T allele, carriers of -455C had higher levels of VLDL-TG (71.4%, p =
      0.0001), reflected in a larger mean VLDL particle size (13.7%, p = 0.009). LIPC
      genotype was not associated with significant effects on any of these traits.
      CONCLUSION: These data confirm the role of genetic variants of CETP, LPL and
      APOC3 in determining the relationship between VLDL, LDL and HDL particles.

PMID- 12514936
TI  - Association of the hormone sensitive lipase -60C > G variant with fasting insulin
      levels in healthy young men.
AB  - BACKGROUND AND AIM: Hormone sensitive lipase (HSL) is the rate-limiting enzyme in
      triglyceride intracellular lipolysis, generating free fatty acids for energy
      utilisation. HSL is also expressed in pancreatic beta-cells where its activity
      may affect insulin secretion. We previously identified an HSL promoter variant, 
      60C > G, which in vitro exhibits 40% reduced promoter activity. METHODS AND
      RESULTS: In this study we examined the association of the HSL -60C > G on fasting
      lipid, insulin and glucose levels and the response to an oral fat tolerance test
      and an oral glucose tolerance test in 744 healthy young men participating in the
      second European Atherosclerosis Study. There was no case control difference in
      frequency of the rare -60G allele, however there was a North-to-South gradient in
      the frequency of the -60G allele, ranging from 0.037 (95% CI 0.01-0.07) in the
      Baltic regions to 0.087 (95% CI 0.05-0.12) in the South of Europe. When the group
      was analysed as a whole, there was no significant difference in fasting lipid or
      glucose values, body mass index, waist/hip ratio or blood pressure and no
      significant heterogeneity between cases and controls. There was, however, a
      significant association with fasting insulin measures [-60CC (n = 608) 11.95 mU/L
      vs -60 CG + GG (n = 79) 10.62 mU/L p = 0.01] and with the homeostasis model
      assessment of insulin resistance (HOMA-IR) (p = 0.04) and the homeostatic
      assessment of beta-cells function (HOMA-B); (p = 0.008). CONCLUSION: Even in
      these healthy young men, HSL-60 C > G allele was associated with effects on
      fasting insulin measures, and differences in insulin resistance and beta-cells
      function.

PMID- 12514937
TI  - Non-obese hyperlipidemic Asian northern Indian males have adverse anthropometric
      profile.
AB  - BACKGROUND AND AIMS: Hyperlipidemia is commonly ascribed to obesity. We studied
      the association of anthropometric profile and nutrient intake with hyperlipidemia
      in non-obese Asian Indian males. METHODS AND RESULTS: In a case-control study,
      non-diabetic, non-obese males with body mass index (BMI) < 25 Kg/m2 having
      primary hyperlipidemia (n = 50) were compared with healthy normolipidemic males
      (BMI < 25 Kg/m2, n = 50). In this study, BMI (p < 0.001), waist circumference
      (WC) (p < 0.001), waist/hip ratio (p < 0.01), skinfolds (p < 0.001), sum of four
      skinfolds (p < 0.001), and percentage of body fat (%BF) (p < 0.001) were
      significantly higher in hyperlipidemic subjects as compared to normolipidemic
      controls. High %BF (> 25%) was observed in 26% of hyperlipidemic subjects and in
      8% normolipidemic controls (p < 0.01). Using analysis of covariance (after
      adjusting for BMI), WC (p < 0.001), %BF (p < 0.01) and %BF/BMI ratio (p < 0.01)
      were significantly higher in the hyperlipidemic subjects. Intakes of total
      calories, total fat, saturated fat, carbohydrates, n-3 and n-6 fatty acids,
      dietary fiber, vitamin E and n-6/n-3 fatty acids ratio were statistically
      comparable between the two groups. In hyperlipidemic subjects biceps skinfold
      correlated negatively to levels of high-density lipoprotein cholesterol (r = 
      0.28, p < 0.05) and serum triglycerides correlated positively to intakes of
      carbohydrate (r = 0.31, p < 0.05), and dietary n-3 fatty acids (r = 0.34, p <
      0.05). CONCLUSIONS: Hyperlipidemic Asian Indian males, defined as "non-obese"
      based on BMI, had adverse profile of anthropometric parameters and excess %BF as
      compared to normolipidemic males. Therefore, while dealing with hyperlipidemic
      Asian Indians, physicians should consider anthropometric parameters (WC), %BF,
      and %BF/BMI ratio in addition to BMI in the clinical assessment.

PMID- 12514938
TI  - Blood levels of total homocysteine in patients with type 1 diabetes (with no
      complications, diabetic nephropathy and/or retinopathy) and in their non-diabetic
      relatives.
AB  - BACKGROUND AND AIM: It has been reported that plasma homocysteine (Hcy) levels in
      type 1 diabetes (T1DM) patients without renal involvement are higher, similar to
      or lower than those in healthy controls. METHODS AND RESULTS: We measured plasma
      Hcy in 60 controls, 79 type 1 diabetics (23 with retinopathy, 22 with
      nephropathy) and 73 non-diabetic relatives of 30 probands. The female controls
      had lower levels than their male counterparts: geometric mean 10.5 vs 13.6
      mumol/L, p < 0.001. Among the controls, smokers (n = 20) and ex-smokers (n = 12)
      had higher Hcy levels than non-smokers (n = 28): 13.2 and 13.2 vs 10.9 mumol/L, p
      < 0.01. Among the diabetics, high plasma Hcy levels were associated with male
      gender: 11.9 vs 9.1 mumol/L in women, p < 0.01. The patients without
      complications had higher plasma glucose and hemoglobin A1c (HbA1c) levels (p <
      0.001), and lower plasma Hcy (9.2 mumol/L vs 12.2, p < 0.01) and uric acid levels
      (p < 0.05) than the controls. The patients with nephropathy and higher levels of
      Hcy (13.0 mumol/L vs 9.0, p < 0.05), and different levels of creatinine (p <
      0.01), uric acid (p < 0.01), fibrinogen (p < 0.05), and urinary albumin (p <
      0.001) than those with retinopathy. There was no difference in Hcy levels between
      the patients' relatives and the controls: 11.9 mumol/L in siblings vs 11.6
      mumol/L, 13.5 mumol/L in parents vs 12.1 mumol/L. In the control group, plasma
      Hcy levels were associated with age, gender and smoking; among the diabetics,
      they correlated with age, gender, smoking, and plasma creatinine and lipoprotein
      (a) levels. CONCLUSIONS: 1) male gender and smoking are associated with high Hcy
      levels in healthy people; 2) plasma Hcy levels are lower in T1DM patients than in
      healthy people (glomerular hyperfiltration and accelerated hepatic
      transsulfuration?); 3) high Hcy levels are associated with diabetic nephropathy
      and plasma creatinine levels; and 4) non-diabetic first-degree relatives of type
      1 diabetics have normal plasma Hcy concentrations.

PMID- 12514939
TI  - Obesity, heart failure and sudden death.
AB  - AIM: To review the direct unfavourable effect of obesity, the most prevalent
      nutritional and metabolic disease worldwide, on cardiovascular morbidity and
      mortality. DATA SYNTHESIS: Obesity is associated with high chronic cardiac
      workload due to the need to supply more blood to peripheral tissue. The high
      cardiac output is mainly a consequence of the greater requirements of increased
      lean body mass, and is maintained by an increased stroke volume and high normal
      heart rate, and sustained by an increase in ventricular mass. The increase in
      left ventricular (LV) mass also implies an increase in non-muscular tissue that
      plays a role in the development of electrical abnormalities, heart failure and
      sudden death. CONCLUSIONS: Obesity per se is a major risk factor for heart
      failure. Obesity-related LV hypertrophy is in turn associated with varying
      degrees of systolic and diastolic dysfunction that are not easily recognisable
      using traditional methods, but are potentially reversible after appropriate,
      stable moderate weight loss.

PMID- 12514940
TI  - A hospital-based network for hyperlipidaemia management and cardiovascular
      disease prevention.
AB  - BACKGROUND AND AIM: A number of studies have shown that there is a wide gap
      between scientific evidence and clinical practice. In particular, less than 50%
      of the patients surviving a myocardial infarction take lipid lowering agents. We
      have developed an organisational model designed to bridge this gap and implement
      clinical guidelines in a clinical setting. METHODS AND RESULTS: We have set up 23
      clinics for the management of hyperlipidaemia and the prevention of
      cardiovascular disease. The procedure for establishing these clinics included the
      training of health staff, the preparation of a medical record, the development of
      a standard operating protocol, the presentation of the aims and operating
      procedure of the network to general practitioners and the community, the
      institution of a freephone number, and the standardisation of quality control.
      The regional clinical network was established in 1998, and examined 1534 patients
      during the first four months. As expected, the most frequent
      hyperlipoproteinaemia was polygenic hypercholesterolaemia (30% of males and 32%
      of females). Fifty-three percent of the 270 patients asking for long-term follow
      up reached an acceptable target according to the international guidelines (total
      cholesterol < 220 mg/dL) in the first two months. CONCLUSIONS: This
      organisational model takes advantage of hospital units, which devote a fraction
      of their time to the prevention of cardiovascular disease. The network is useful
      for standardising diagnostic and therapeutic procedures in accordance with the
      guidelines, and has an educational impact on both patients and health staff. The
      availability of a large database of patients with hyperlipoproteinaemia is the
      basis for quality control, drug safety surveillance, and clinical studies of
      specific issues or selected patient subgroups. The hospital-based network is an
      operational reference for all practitioners in the region and helps to integrate
      efforts aimed at bridging the gap between scientific evidence and clinical
      practice.

PMID- 12514941
TI  - Dried white grapes enhance blood antioxidant potential.

PMID- 12514942
TI  - Chinese phlebotomine sandflies of the subgenus Adlerius Nitzulescu, 1931
      (Diptera: Psychodidae) and the identity of P. sichuanensis Leng & Yin, 1983. II-
      genotyping and numerical analysis.
AB  - The authors carried out isoenzyme characterization and genotype comparison
      studies for Phlebotomus chinensis and Phlebotomus sichuanensis images collected
      from their holotype/paratype original localities: West Mountain, West Suburb,
      Beijing and Lixian County, Sichuan Province. Numerical analysis was carried out
      and the dendrogram of four species of Adlerius was drawn up according to
      morphological characteristics of these four species. The results showed that P.
      chinensis and P. sichuanensis can be identified enzymatically in PGM and the MDH
      2 allele also differs in P. chinensis from Beijing and. P. sichuanensis. The
      dendrogram of four Adlerius species showed that P. fengi and P. longiductus are
      very similar and they clustered first, then P. sichuanensis combine with them to
      form a combined group. P. chinensis is a separate group from other three. These
      two groups come to combine at last. Above results have proved that P.
      sichuanensis is an isolate species instead of a so-called large type P.
      chinensis.

PMID- 12514943
TI  - Diversification of Cercopithifilaria species (Nematoda: Filarioidea) in Japanese
      wild ruminants with description of two new species.
AB  - Twelve of the 17 Cervus nippon nippon deer from Kyushu Island, Japan, that we
      examined were infected with one or two Cercopithifilaria species. C. longa n. sp.
      adults were in the subcutaneous tissues of limbs and the abdomen, and C. crassa
      n. sp. adults were in the skin, mainly in the anterior part of the back; the
      distribution of the dermal microfilariae generally matched that of the adult
      worms. The two new species were assigned to the group of primitive
      Cercopithifilaria species that parasitize ruminants (bavids and cervids), but the
      new species could readily be distinguished from others morphologically. C. longa
      was more primitive and resembled C. bulboidea, one of the five species from the
      serow Capricornis crispus, a Japanese member of the Caprinae, and species from
      Bovidae in Africa. C. crassa had a thick body and large spicules like C.
      rugosicauda from Capreolus capreolus in Europe, the only previously known
      Cercopithifilaria species from cervids, but it also had one or two hypertrophied
      pairs of caudal papillae, an unusual character found so far only in Japanese
      parasites. Among the 12 species known from ruminants, four are African, one is
      European and more highly evolved, and seven are Japanese, with some being
      primitive and some more evolved. The great diversity of Cercopithifilaria species
      in the two wild ruminants that live in Japan seems to have resulted from local
      speciation, which occurred during the Pleistocene, from a primitive form of the
      C. longa type derived from Eurasiatic ancestors, which has disappeared or, more
      probably, not yet been discovered.

PMID- 12514944
TI  - Description of Paranoplocephala etholeni n. sp. (Cestoda: Anoplocephalidae) in
      the meadow vole Microtus pennsylvanicus, with a synopsis of Paranoplocephala s.
      l. in holarctic rodents.
AB  - Paranoplocephala etholeni n. sp., parasitizing the meadow vole Microtus
      pennsylvanicus in Alaska and Wisconsin, USA, is described. Paranoplocephala
      etholeni is morphologically most closely related to the Nearctic Paranoplocephala
      ondatrae (Rausch, 1948). Available data suggest that P. etholeni is a host
      specific, locally rare species that may have a wide but sporadic geographical
      distribution in North America. The finding of P. ondatrae-like cestodes in
      Microtus spp. suggests that this poorly known species may actually be a parasite
      of voles rather than muskrat (type host). A tabular synopsis of all the known
      species of Paranoplocephala s. l. in the Holarctic region with their main
      morphological features is presented.

PMID- 12514945
TI  - Monogeneans from Pangasiidae (Siluriformes) in Southeast Asia: IV. Five new
      species of Thaparocleidus Jain, 1952 (Ancylodiscoididae) from Pangasius krempfi,
      P. kunyit, P. mekongensis and P. sabahensis.
AB  - The examination of gill parasites from Pangasius krempfi Roberts & Vidthayanon,
      1991; P. kunyit Pouyaud et al., 1999; P. mekongensis Gustiano et al., in press
      and P. sabahensis Gustiano et al., in press (Siluriformes, Pangasiidae) in
      Southeast Asia revealed the presence of six species of Monogenea, all belonging
      to the genus Thaparocleidus Jain, 1952 (Monogenea, Ancylodiscoididae) as defined
      by Lim (1996) and Lim et al. (2001). One has been previously described (T.
      vietnamensis Pariselle et al., 2002), five are considered as new species: T.
      humerus n. sp. and T. culter n. sp. on P. kunyit; T. mehurus n. sp. and T.
      culteroides n. sp. on P. sabahensis; and T. phuongi n. sp. on the four studied
      host species. The latter one, due to slight morphometric differences linked to
      geographical origin of hosts, is described as made up of three sub-species: T.
      phuongi phuongi n. sub-sp., T. phuongi malaysiensis n. sub-sp. and T. phuongi
      indonesiensis n. sub-sp.

PMID- 12514946
TI  - [First record of Phlebotomus from Madagascar (Diptera: Psychodidae). Description
      of Phlebotomus (Anaphlebotomus) fertei n. sp. and Phlebotomus (Anaphlebotomus)
      huberti n. sp].
AB  - First record of Phlebotomine sandflies belonging to the genus Phlebotomus from
      Madagascar. Description of two new species: Phlebotomus (Anaphlebotomus) fertei
      n. sp. from three males and Phlebotomus (Anaphlebotomus) huberti n. sp. from two
      females. Their belonging to the subgenus Anaphlebotomus is supported by several
      characters. Male have four spines on the style, a coxite without basal tubercle,
      a paramere with two branches, one to three antero-inferior setae on the
      mesanepisternum. Female, closely related to the Asiatic species of the same
      subgenus, has a characteristic pharyngeal armature, about ten cibarial teeth, and
      annealing spermathecae with long ducts including a short basal common part. These
      two taxa differ by variation in the second internal transcribed spacer (ITS2) of
      the ribosomal DNA (rDNA). At the present time, the subgenus Anaphlebotomus
      includes six species (excluding P. fortunatarum from it), completing the known
      species from Africa (P. rodhaini and P. rousettus) and from Asia (P. stantoni and
      P. colabaensis).

PMID- 12514947
TI  - Eosinophil and mast cell expression in host skin during larval development of the
      human bot fly Dermatobia hominis.
AB  - Eosinophils and mast cells in the skin of Wistar rats (Rattus norvegicus)
      infested with Dermatobia hominis larvae were quantified and analysed. Eosinophils
      in parasitised skin increased markedly until 10 days post-infestation (dpi) and
      then decreased up to 28 dpi, close to the point at which third stage larvae (L3)
      emerged from the host. In ascending order, the highest numbers of eosinophils
      were seen in rats at 1, 4, 28, 20, 15 and 10 dpi, corresponding to the first, (1
      and 4) third (20 and 28) and second (10 and 15) instars. Except for 1 dpi,
      eosinophil numbers were significantly higher than those seen in control animals.
      Mast cell numbers were highest in early infestation (4 dpi), followed by those at
      20 dpi. In increasing order, numbers of mast cells were greatest at 10, 28, 15,
      1, 20 and 4 dpi, although significant differences with control animals were only
      seen at 10 and 28 dpi. Eosinophils and mast cells showed negative correlation
      only in animals with second instar larvae (10 and 15 dpi). Comparative analyses
      were also carried out after considering the skin into four distinct regions. The
      results suggest that the expression of both cell types, particularly eosinophils,
      is an important host response to infestation by D. hominis.

PMID- 12514948
TI  - Caryospora matatu n. sp., a new coccidian parasite (Apicomplexa: Eimeriidae) from
      the horned bush-viper, Atheris ceratophorus Werner, 1895 from Tanzania.
AB  - Caryospora matatu n. sp. is the first species of coccidia reported from the a
      horned bush viper, Atheris ceratophorus endemic to Tanzania. Oocysts are
      spherical or slightly subspherical, 19.8 (16-23) microns, a micropyle and an
      oocyst residuum are absent, a single polar granule is present. An oocyst wall is
      bilayered, approximately 1.5 microns thick, brownish and distinctly pitted.
      Sporocysts are ellipsoidal, 15.6 (12.5-17.0) x 10.1 (8-12) microns, tightly
      fitting an internal oocyst diameter, Stieda and substieda bodies are present. An
      experimental inoculation of SCID mice did not confirm a facultatively
      heteroxenous life cycle in the studied coccidium. Morphology and evolutionary
      history of Caryospora species from viperids is is reviewed and discussed.

PMID- 12514949
TI  - Identification of trypanosomes in wild animals from southern Cameroon using the
      polymerase chain reaction (PCR).
AB  - One possible explanation of the maintenance of many historical foci of sleeping
      sickness in Central Africa could be the existence of a wild animal reservoir. In
      this study, PCR was used to detect the different trypanosome species present in
      wild animal captured by hunters in the southern forest belt of Cameroon
      (Bipindi). Trypanosomes were also detected by a parasitological method
      (Quantitative buffy coat: QBC). Parasite could not be isolated in culture medium
      (Kit for in vitro isolation: KIVI). Specific primers of T. brucei s.l., T.
      congolense forest type, T. congolense savannah type, T. vivax, T. simiae and T.
      b. gambiense group 1 were used to identify parasites in the blood of 164 animals
      belonging to 24 different species including ungulates, rodents, pangolins,
      carnivores, reptiles and primates. Of the 24 studied species, eight were carrying
      T. b. gambiense group 1. Those parasites pathogenic to man were found in monkeys
      (Cercocebus torquatus and Cercopithecus nictitans), in ungulates (Cephalophus
      dorsalis and C. monticola), in carnivores (Nandinia binotata and Genetta
      servalina) and in rodents (Cricetomys gambianus and Atherurus africanus). 13
      species (54%) were carrying T. brucei s.l. identified as non-gambiense group 1.

PMID- 12514950
TI  - Echinococcus granulosus down regulates the hepatic expression of inflammatory
      cytokines IL-6 and TNF alpha in BALB/c mice.
AB  - Hydatid disease is caused by the metacestode of Echinococcus granulosus.
      Different experimental models have been used to understand hydatid disease. In
      current studies BALB/c mice were used to evaluate the hepatic response of IL-6
      and TNF alpha triggered by Echinococcus granulosus. BALB/c mice were
      intraperitoneally infected with protoscoleces from E. granulosus; hydatid cysts
      appeared on the liver eight weeks after inoculation. The RNA extracted from
      hepatic sections was used for RT-PCR amplification with primers for IL-6, TNF
      alpha, IL-10, TGF beta and G3PDH. In situ cytokine expression was assessed by
      FISH. Complete parasite cysts on the liver surface were observed 16 weeks after
      infection; controls were negative. The expression of IL-6 and TNF alpha was
      normal at baseline and declined progressively eight weeks after infection; in
      some animals such expression was abrogated 16 weeks after infection. On the other
      hand IL-10 and TGF beta were increased progressively. Controls expressed the
      cytokines normally. Present results suggest that E. granulosus induces a local
      immunosupression probably mediated by IL-10 and TGF beta; therefore it seems
      possible that such a mechanism would assist the parasite in escaping the harmful
      host cell-mediated response.

PMID- 12514951
TI  - [Variability according to the individual of the efficacy of repellents with a
      base of vegetable oils in the individual protection against Simulium damnosum s.
      l. bites].
AB  - In Ivory Coast, treatments against black flies larva are interrupted since
      December 1998 and these flies are back everywhere in abundance. They are now a
      severe source of discomfort, so it is therefore very important to propose to
      rural populations a personal protection method against their bites. This article
      is about the individual attraction of fly boys on the efficiency of lotions and
      creams of the different repellents (coconut, palm nut, gobi). Our works were
      carried out in savanna zone (Niakaramandougou) and in forest zone (Soubre) in
      Ivory Coast. The methodology consisted in capturing black flies on volunteers
      whose legs were rubbed with repellent. Coconut, palm nut and gobi formulas
      (lotions and creams) were tested on Simulium damnosum s.l. During each session,
      which lasted from 07:00 am to 12:00 and from 03:00 pm to 06:00 pm, one person
      without repellent was used as a control person. The results show that the least
      efficient repellent (gobi) ensures nonetheless a reduction of 90% of the number
      of bites that an individual would have received if he was not protected by the
      repellent. Experimentations allows to say that for a given repellent and formulas
      (lotion and cream), there is no significant difference between the number of
      Simulium damnosum s. l. bites received by fly boys.

PMID- 12514952
TI  - Kinetics of antibody response by Dot-ELISA in rabbits immunized with adult
      Haemonchus contortus antigen.
AB  - Whole adult soluble extract of Haemonchus contortus as an antigen along with
      Freund's complete adjuvant, was used to immunize rabbits. Antisera from immunized
      rabbits were collected at intervals of 30, 60, 90, 120, 150 and 180 days. For the
      detection and titration of anti-H. contortus antibodies in these sera, Dot-ELISA
      was developed. Sera collected 30 days post-immunization exhibited a titre of
      1:5,000 in all the rabbits except one, where a titre of 20,000 was recorded.
      Later, all the rabbits attained the highest titre of 40,000 at different periods
      of post-immunizations, which were maintained 150-180 days. These high titre sera
      can be of immense use in the identification and characterization of
      immunodominant antigens of adult H. contortus.

PMID- 12514953
TI  - In vitro and in vivo antileishmanial activity of 2-amino-4,6-dimethylpyridine
      derivatives against Leishmania mexicana.
AB  - Leishmania mexicana promastigote and intracellular amastigote growths were
      inhibited by the water-soluble furan-2-carboxamide issued from the pharmacophore
      2-amino-4,6-dimethylpyridine with IC50 values of 69 +/- 2 and 89 +/- 9 microM,
      respectively. This compound was also tested against established L. mexicana
      infection in susceptible BALB/c mice; an intraperitoneal administration of 10
      mg/Kg/day during five consecutive days induced a high reduction in the amastigote
      burden of the poplitea lymph node (81 +/- 6.4%), the spleen (80 +/- 1.6%) and the
      liver (73 +/- 9%). Approach of the mechanism of antileishmanial activity of this
      compound, assessed by the flow cytometry, showed a reduction in the protein and
      DNA synthesis. Finally, an actual increase of the in vitro antileishmanial
      activity was obtained by replacement of the amidic function by an imidazolidin-2
      one moiety. In this new series, two of the N-substituted derivatives showed IC50
      values of 13 +/- 0.5 and 7 +/- 3 microM in intracellular amastigotes constituting
      new promising compounds for further studies.

PMID- 12514954
TI  - The role of nitric oxide and lipid peroxidation in patients with Plasmodium vivax
      malaria.
AB  - In this study, we investigated the role of nitric oxide metabolism and lipid
      peroxidation in patients with P. vivax malaria. The levels of nitrite and nitrate
      were analyzed using a procedure based on the Griess reaction and malondialdehyde
      levels which index of lipid peroxidation was determined by thiobarbituric acid
      reaction. The levels of nitrite/nitrate and malondialdehyde in patients were
      higher than controls and found to be statistically significant (p < 0.001). We
      performed this study to determine whether nitric oxide and lipid peroxidation is
      produced during blood-stage P. vivax malaria. This present study shows that lipid
      peroxidation occurs in P. vivax malaria. The levels of nitric oxide are
      associated with lipid peroxidation in this disease.

PMID- 12514955
TI  - Transferrin coupled azanthraquinone enhances the killing effect on trypanosomes.
      The role of lysosomal mannosidase.
AB  - Partially purified azanthraquinone (AQ) extract from Mitracarpus scaber was
      coupled to bovine transferrin (Tf) using azidophenyl glyoxal (APG). The AQ-APG-Tf
      conjugate was found to possess an enhanced in vitro trypanocidal activity against
      Trypanosoma congolense and T. brucei brucei. At low concentrations of 0.39-90
      mg/ml, the conjugate diminished the growth of T. congolense and T. b. brucei dose
      dependently at the logarithmic phase. Both parasites were more sensitive to AQ
      APG-Tf than to the free (AQ) extract. Growth inhibition on the parasites by the
      free extract was observed at 20-200 mg/ml. The total activity of the lysosomal
      enzyme a-mannosidase was reduced in the T. congolense cells treated with AQ-APG
      Tf in a dose related pattern. However, the activity of the mannosidase in the T.
      b. brucei treated cells is less affected. The AQ-APG-Tf is more effective on a
      mannosidase than free AQ, eight and four fold for T. congolense and T. b. brucei
      respectively. The results are discussed as regards the potency of using
      transferrin as suitable drug carrier in the chemotherapy of Human sleeping
      sickness.

PMID- 12514956
TI  - The advanced practice payment scandal.

PMID- 12514957
TI  - Flu jabs not suitable for all.

PMID- 12514958
TI  - Should there be a total ban on smoking in public places?

PMID- 12514959
TI  - Settling the new agenda.

PMID- 12514960
TI  - A brief guide to the new supplementary prescribing.
AB  - Supplementary prescribing is an entirely new way of prescribing medicines,
      involving a partnership between a doctor (the independent prescriber) and a nurse
      or pharmacist (the supplementary prescriber). Following the announcement in
      November 2002 by health minister Lord Philip Hunt, this article explains how
      supplementary prescribing will work and looks at where and how nurses can use
      this new form of prescribing to improve services to patients.

PMID- 12514962
TI  - Postoperative epidural analgesia.

PMID- 12514961
TI  - What you need to know about ... tuberculosis.

PMID- 12514963
TI  - Diagnosis and management of candidiasis vaginitis.
AB  - Candidiasis vaginitis (vaginal thrush) is a common fungal infection that can be
      treated with an antifungal agent. It can be a distressing condition, especially
      if recurrent infections are experienced. Successful treatment requires attention
      to underlying contributing factors, education about preventive measures and the
      dispelling of the many myths associated with the condition.

PMID- 12514964
TI  - The benefits of implementing an electronic patient record system.
AB  - The national information strategy information for Health outlined the strategic
      objective: to ensure clinicians have access to relevant information 24 hours a
      day, seven days a week. Electronic patient record (EPR) systems are the key to
      achieving this in the short term and are also the basis for the migration from
      paper to electronic records in the future. This article outlines the development
      of a new nurse role to participate in the procurement process and subsequent
      implementation of the EPR system in an acute trust.

PMID- 12514965
TI  - Network nurse.

PMID- 12514966
TI  - High flyers.

PMID- 12514967
TI  - Anti-emetics.

PMID- 12514968
TI  - Using antibacterial drugs.

PMID- 12514969
TI  - Taking a holistic approach.

PMID- 12514970
TI  - Opening the door to first-contact care.

PMID- 12514971
TI  - Identification of Acinetobacter species isolated from clinical specimens by
      amplified ribosomal DNA restriction analysis.
AB  - BACKGROUND & OBJECTIVES: Taxonomy of Acinetobacter has been changing ever since
      it was recognized to be associated with human infections. Many biochemical
      schemes and molecular methods have been used for the species identification of
      this bacterium. Recently a simple molecular method called amplified ribosomal DNA
      restriction analysis (ARDRA) has been used to determine the genomospecies of
      ACINETOBACTER: An attempt is made in the present study to identify the
      Acinetobacter genomospecies isolated from clinical specimens using ARDRA and to
      see whether the environmental isolates are similar to those obtained from
      clinical specimens. METHODS: A total of 142 consecutive isolates of Acinetobacter
      sp. obtained from different clinical specimens (125) and environmental samples
      (17) of postoperative neurosurgery-intensive care unit were studied using ARDRA.
      Amplification was done using primers of 16S rRNA gene followed by restriction
      with Alu I, Cfo I and Mbo I enzymes separately to obtain a profile of patterns
      specific for a species. RESULTS: Of the 125 clinical isolates, 107 were
      Acinetobacter baumannii (genomospecies 2) and 18 were A. calcoaceticus
      (genomospecies 1); while 11 of the 17 environmental isolates were A. baumannii
      and 6 had unidentifiable patterns which were not found in the clinical isolates.
      INTERPRETATION & CONCLUSION: We found that ARDRA was a simple and reproducible
      method to be used in a clinical laboratory for identification of Acinetobacter
      species. A. baumannii was found to be the commonest species isolated from the
      patients and environment in our hospital. The presence of the same species of
      Acinetobacter in the environment suggests the role of environment as a source of
      infection to the patients in high risk units.

PMID- 12514972
TI  - Change in distribution & antifungal susceptibility of Candida species isolated
      from candidaemia cases in a tertiary care centre during 1996-2000.
AB  - BACKGROUND & OBJECTIVES: As a marked increase in the number of patients with
      candidaemia was reported in the first half (1991-1995) of the last decade at the
      Postgraduate Institute of Medical Education & Research, Chandigarh, India, the
      present study was aimed at determining further change if any, in the incidence
      and distribution of Candida species and their antifungal resistance pattern
      during the second half (1996-2000) of the same decade. METHODS: The patients with
      candidaemia were studied to determine the frequency of candidaemia and Candida
      species isolated during 1996-2000. One hundred Candida strains other than Pichia
      anomala (C. pelliculosa) were randomly selected from those isolates to evaluate
      antifungal susceptibility pattern against amphotericin B, 5-fluorocytosine,
      ketoconazole, fluconazole and itraconazole. The results were compared with our
      previous study. RESULTS: An increase in the number of patients with candidaemia
      was observed during 1996 (538) and 1997 (421) compared to 1998-2000 due to P.
      anomala outbreak. With the control of the outbreak, a substantial decrease in the
      incidence of candidaemia was observed from 1998 (251 in 1998, 122 in 1999 and 165
      in 2000). A higher isolation of non-C. albicans Candida species (89.8%) was
      observed, with C. tropicalis being the most common (541, 36.1%) agent. No major
      change in the isolation rate of other non-C. albicans Candida species (C.
      guilliermondii, C. krusei, C. glabrata and C. parapsilosis) was observed. An
      emergence of resistance to amphotericin B in 15.4 per cent C. albicans, 8.1 per
      cent C. tropicalis and 33.3 per cent C. krusei strains was observed. An increase
      in resistance to ketoconazole (from 0% to 13%) and 5-fluorocytosine (from 1% to
      8%) and a decrease to fluconazole (from 13% to 6%) were observed. Resistance to
      itraconazole was observed in 17 per cent of Candida strains by broth macro
      dilution method. INTERPRETATION & CONCLUSION: A change in the isolation of
      Candida species was observed i.e. in the incidence and isolation of non-C.
      albicans Candida species. Emergence of resistance to amphotericin B and increase
      of resistance to most other antifungals are cause for concern.

PMID- 12514973
TI  - Mannan antigen detection in the diagnosis of patients with invasive candidiasis.
AB  - BACKGROUND & OBJECTIVES: With the increase in the incidence of invasive
      candidiasis (IC) in recent years, there is a need to improve the sensitivity of
      diagnosis. A conventional technique like blood culture is positive in nearly 50
      per cent of cases. To improve the diagnostic efficiency in invasive candidiasis
      mannan antigen detection holds promise. Hence mannan antigen detection was
      evaluated in patients with suspected invasive candidiasis in the Paediatric
      Intensive Care Unit (PICU). METHODS: A prospective study, involving 186
      consecutive patients admitted to the PICU of the Advanced Paediatric Center at
      the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh
      between March 1999 and November 1999 were followed up for possible invasive
      candidiasis. Sixty five children clinically suspected to have sepsis and at risk
      for developing IC and or who stayed in the hospital more than 5 days were further
      evaluated for the diagnosis of IC by collecting two blood culture samples 48 h
      apart and by mannan antigen and anti-mannan antibody detection. Both antigen and
      antibody were detected by in-house standardized techniques: antibody by whole
      cell agglutination (WCA) and antigen by sandwich enzyme linked immunosorbent
      assay (ELISA). RESULTS: Twenty of 65 patients (30.7%) were positive by blood
      culture. Mannan antigen was positive in all 20 patients and significant anti
      mannan antibody titre (> or = 128) was present in 12 (60%) patients. Mannan
      antigen was detected in 15 more patients, who were negative for isolation of
      Candida from blood. Twelve of these patients had febrile episode not responding
      to antibacterial therapy but responding to fluconazole/itraconazole therapy
      indicating that the patients possibly had IC. Mannan concentration was also found
      to be significantly higher in the patients with Candida isolated from blood.
      INTERPRETATION & CONCLUSION: Thus, the present study confirms the earlier claim
      that mannan antigen detection possibly improves the diagnostic efficiency of IC.

PMID- 12514974
TI  - Prevalence of psychiatric disorders in school children in Chandigarh, India.
AB  - BACKGROUND & OBJECTIVES: Population studies on the prevalence of psychiatric
      disorders among children and adolescents in different countries of the world,
      have reported varying rates of disorders. There are very few studies in India and
      these vary widely in methodology and reported rates of disorders. The main
      objective of this research was to study the extent and nature of psychiatric
      disorders in school children in a defined geographical area and to study their
      psychosocial correlates. METHODS: School children, aged 4-11 yr, in the city of
      Chandigarh, were studied using multi-stage random sampling, and multi-informant
      assessment procedure. Teachers assessment on Rutter-B Scale (Stage I) was
      followed by parent interview (Stage II) for all children on the Childhood
      Psychopathology Measurement Schedule which is an Indian adaptation of Achenbach's
      Childhood Behaviour Checklist (CBCL). Children scoring above the cut-off at Stage
      I and/or Stage II were assessed clinically by two psychiatrists (Stage III) who
      interviewed parents as well as the child taking detailed clinical history and
      mental state examination including IQ assessment. RESULTS: 6.33 per cent of the
      children studied (n = 963) were found to have psychiatric disorders on ICD-10
      criteria. Teacher's estimation of the prevalence rates was higher, i.e., 10.17
      per cent as compared to parent's estimate i.e., 7.48 per cent. The most prevalent
      disorder was enuresis. INTERPRETATION & CONCLUSION: This study provides data for
      comparative epidemiology and highlights issues relating to cultural context of
      disorders in child psychiatric epidemiology.

PMID- 12514975
TI  - Immediate treatment of frostbite using rapid rewarming in tea decoction followed
      by combined therapy of pentoxifylline, aspirin & vitamin C.
AB  - BACKGROUND & OBJECTIVES: Frostbite, the severest form of cold injury is a serious
      medical problem for our Armed Forces operating in the snow bound areas at high
      altitude. Effects of treatment by rapid rewarming in tea decoction followed by
      combined therapy of pentoxifylline, aspirin and vitamin C were evaluated in
      amelioration of tissue damage due to experimentally induced frostbite in rats.
      METHODS: Experiments were conducted in 2 groups (25 each) of albino rats (control
      i.e., untreated and experimental i.e., treated). Frostbite was produced
      experimentally in all the animals by exposing one of the hind limbs at -12 +/- 1
      degree C with wind flow 25-30 lit/min for 30 min in a freezing-machine, with
      simultaneous recordings of rectal and ambient temperatures. The degree of tissue
      damage was assessed after 10 days. Following cold exposure, neither external
      thawing nor any medication was given to the animals of the control group; while
      the exposed limb of the experimental animals was rewarmed in tea decoction
      maintained at 37-39 degrees C for 30 min immediately after cold exposure, with
      simultaneous oral ingestion of warm tea decoction. These animals were also given
      pentoxifylline (40 mg/kg), aspirin (5 mg/kg) and vitamin C (50 mg/kg) twice daily
      orally for the next 7 days. RESULTS: In the control group, 68 per cent animals
      suffered from severe (56%) to very severe (12%) frostbite, while the remaining 32
      per cent had moderate frostbite. No animals of this group could escape injury or
      suffered anything less than moderate frostbite; whereas 52 per cent of
      experimental animals escaped injury (no frostbite) and 32 and 16 per cent
      suffered only with primary and moderate degree of injury, respectively. None from
      this group suffered from severe or very severe frostbite. INTERPRETATION &
      CONCLUSION: It is evident from the study that this combined therapy resulted in
      significant improvement in the degree of tissue preservation and proved to be
      highly beneficial as an immediate treatment of frostbite in rats. The combined
      pharmacological properties of these drugs might have altered the haemorrheologic
      status of blood and produced curative beneficial effect in improving tissue
      survival. Clinical studies are required for confirmation of these beneficial
      effects in humans, which has already been taken up.

PMID- 12514977
TI  - The health care community crisis.

PMID- 12514976
TI  - Hippocampal hyperexcitability facilitates amygdala kindling in rats.
AB  - BACKGROUND & OBJECTIVES: The amygdala and hippocampus are recognized as the two
      important structures in the brain involved in the development and control of
      kindled seizures. The study on the precise interconnection between these two
      regions can provide important insights into the functional anatomy of complex
      partial seizures. In this study the effect of an experimentally increased
      excitability in hippocampal neurons, via hippocampal kindling, on the amygdala
      kindling rate was investigated in rats. METHODS: Animals were divided into four
      groups. Tripolar electrodes were implanted in the amygdala and CA1 region of the
      dorsal hippocampus of animals of Groups 1, 3 and 4. In Group 2 animals, tripolar
      electrodes were only implanted in the amygdala. In Group 1, one week after
      surgery, the rats were kindled first from the hippocampus and the next day
      kindled by amygdala stimulation. In Groups 2 and 3, one week after surgery, rats
      were kindled from the amygdala. Group 4 animals had a recovery period of one week
      plus 32 days, which was the mean of the hippocampal kindling rate in Group 1, and
      then were kindled from the amygdala. RESULTS: In Group 1, the amygdala kindling
      rate (n; number of days for which animals were stimulated before a stage 5 motor
      convulsion is triggered) and seizure stage at day n/2 were significantly
      facilitated and increased respectively. There was also a significant positive
      correlation between hippocampal and amygdala kindling rates. INTERPRETATION &
      CONCLUSION: Results obtained show that an increase in hippocampal excitability
      can facilitate kindling from the amygdala. Thus, it is suggested that the
      hippocampus has an important role in the development and propagation of seizures
      from the amygdala.

PMID- 12514978
TI  - Holding ourselves and others accountable.

PMID- 12514979
TI  - Frequently asked questions about breakthrough to nursing.

PMID- 12514980
TI  - Are we solving the nursing shortage, or creating one?

PMID- 12514981
TI  - Is entrepreneurship for you?

PMID- 12514982
TI  - Entrepreneurship with a social conscience.

PMID- 12514983
TI  - How to become a legal nurse consultant.

PMID- 12514984
TI  - Feeding the ill or preterm infant.
AB  - Illness and immaturity often interfere with a neonate's ability to receive full
      enteral feedings during the first week of life. The goals of feeding in the NICU
      are to nourish the preterm infant for appropriate growth and development and to
      facilitate the earliest possible discharge from the NICU. Early, small-volume
      feedings, or trophic feedings, have been studied as a method for achieving these
      goals. The high-risk infant given such trophic feedings not only receives minimum
      enteral nutrition, but also attains earlier full nutritional feedings and,
      consequently, is discharged home earlier. Oro- or nasal-gastric gavage feedings
      are usually indicated for this group of infants because of their physiologic
      immaturity and the frequent presence of respiratory illness. Recent studies
      support the use of intermittent bolus feedings, which have long been used for the
      premature infant. Several authors have noted advantages to continuous infusions
      as well. Because the infant is unable to pace or refuse gavage feedings, the
      caretaker must determine the appropriate volume of each feeding. The optimal
      volume for initiation and advancement of trophic and nutritional feedings is
      still under investigation, but reports have demonstrated safe volumes for even
      the extremely premature infant.

PMID- 12514985
TI  - Partnerships between mothers and professionals in the NICU: caregiving,
      information exchange, and relationships.
AB  - PURPOSE: The purpose of this study was to examine the perspectives of mothers,
      nurses, and neonatologists on the importance and implementation of NICU practices
      related to caregiving, information exchange, and relationships within the context
      of family-centered care. DESIGN: This study design was descriptive. The PARTNERS
      Questionnaire was developed and implemented, including both quantitative and
      qualitative items in the three areas (caregiving, information exchange,
      relationships). For the parent participants, it was a retrospective study.
      SAMPLE: Two hundred fifteen questionnaires were distributed to professionals and
      157 questionnaires were mailed to mothers of NICU graduates. A total of 196
      questionnaires (53 percent) was returned (55 mothers, 18 neonatologists, and 123
      nurses). RESULTS: Ratings of importance to the respondent and ratings of degree
      of implementation of items in the three areas were uniformly high. Mothers and
      nurses had significantly higher ratings than neonatologists in implementation of
      caregiving. In addition, mothers and nurses rated importance higher than
      implementation for the areas of information exchange and relationships.

PMID- 12514986
TI  - Divine secrets of the yo-yo sisterhood.

PMID- 12514987
TI  - Free radicals.
AB  - Free radicals may be the cause of many neonatal complications, such as chronic
      lung disease and brain injury. Treatment options for these complications using
      antioxidants are being evaluated through research. This article begins with a
      review of the basic science of free radicals. It then discusses neonatal
      complications potentially caused by free radicals. A brief description of
      research into potential treatment options is also included.

PMID- 12514988
TI  - Inguinal hernia in the premature infant: management of a common problem.
AB  - Inguinal hernia repair is one of the most common surgical procedures performed on
      premature infants. Improved survival rates in the NICU have led to an increase in
      the incidence of premature infants with inguinal hernias. The NICU nurse, often
      the first to notice an inguinal hernia in a premature infant, should understand
      the etiology, basic pathophysiology, and nursing care for this condition.

PMID- 12514989
TI  - Protecting the international traveller.

PMID- 12514990
TI  - Notice of proposed bylaw changes.

PMID- 12514991
TI  - Safe driving: a workplace issue for RNs too.

PMID- 12514992
TI  - Carboxy-methyl-cellulose hydrogel mammary implants: our experience.
AB  - The Authors present their experience with carboxy-methyl-cellulose hydrogel
      mammary implants. 110 patients have undergone operations since October 1998 with
      the implantation of this type of prosthesis. The results are very good: no major
      complications, and only 22 patients (20%) showed a II stage capsular contracture
      and 4 patients (3.6%) a III stage, according to Baker's scale, with an average
      follow-up of 20 months. The low percentage of capsular contracture and the
      absence of major complications, let us to conclude that this type of implant is
      highly tolerated by the human body.

PMID- 12514993
TI  - An unusual broken breast implant.
AB  - The Authors describe the case of a 40-year-old woman with a ruptured carboxi
      methyl-cellulose mammary implant. The utilisation of this type of implants will
      spread rapidly, so it is very important to diffuse knowledge about these. The
      Authors conclude that carboxi-methyl-cellulose hydrogel, as a filler, is a valid
      alternative to silicone and saline solution (4, 5).

PMID- 12514994
TI  - Surgical treatment of peripheral nerve injuries in upper extremities.
AB  - OUTLINE: This study presents the results of surgical treatment of nerves in upper
      extremities performed in our clinic over 15 years, from 1985 to 1999. Basic lines
      of surgical treatment of various injuries of nerves in upper extremities are
      presented and evaluated in the study. SYNOPSIS AND METHODS: 140 nerves in 123
      patients were treated within this period. 95 reconstruction operations were
      performed by microsurgical technique in 95 patients. All reconstruction surgery
      was performed in cases characterized by complete and persisting neurological
      deficit and by the absence of action potentials in relevant nerves. In 42
      patients, 45 nerves were reconstructed by an autologous nerve graft. In 53
      patients, reconstruction surgery was performed by suture of peripheral nerve that
      included treatment of 65 nerves. In this group, 10 patients were treated by
      suturation of 2 nerves and 3 nerves were suturated in one patient. In 28
      patients, external neurolysis was the final surgical therapeutic treatment. In
      this group, neurolysis of 2 nerves was performed in 2 patients. The presence of
      action potential was always an important criterion in the determination of the
      type of surgical intervention. The analysis of the effectiveness of surgical
      intervention was performed with respect to: the period elapsed between injury and
      operation age of the patient character of injury location of injury category of
      injured nerve type of surgical intervention RESULTS: The best results were
      observed for external neurolysis and for n. medianus. Evaluation of the
      effectiveness of neural suture did not reveal any significant differences between
      neural grafts and classical suture. Similar results were obtained for surgical
      treatment of isolated nerve injuries and for cases involving the reconstruction
      of more than one nerve. Good or excellent results were typical for early
      treatment, for distal injuries and for clean incised wounds, especially in young
      patients. CONCLUSION: Early surgical revision combined with neurolysis and
      reconstruction surgery (if necessary) are crucial factors determining the outcome
      of operation in indicated cases. With respect to reconstruction operations we did
      not observe any significant difference between classical suture and suture using
      nerve graft.

PMID- 12514995
TI  - An alternative video footprint analysis to assess functional loss following
      injury to the rat sciatic nerve.
AB  - The rat sciatic nerve is a well-established animal model for the study of
      recovery from peripheral nerve injuries. Footprint analysis is the most widely
      used non-invasive method of measuring functional recovery after injury in this
      model. We describe a new, alternative video analysis of standing (or static
      footprint video analysis) to assess functional loss following injury to the rat
      sciatic nerve, while the animal is standing or at periodic rest on a flat
      transparent surface. We found that this alternative video analysis is technically
      easier to perform than the corresponding footprint video analysis while walking,
      but still preserves all advantages of video versus conventional ink track method:
      i.e. few non-measurable footprints, better repeatability, high accuracy and more
      precise quantification of the degree of functional loss after sciatic nerve
      injury in the rat.

PMID- 12514996
TI  - The importance of stored supplies of biological skin covers in territorial
      management of mass burn casualties.
AB  - This study provides supportive evidence of a possible role played by planning
      supplies of biological covers needed in fire disaster, based on the experience of
      the authors. The major steps to be taken are these: 1. Providing a technically
      and technologically adequate base for collection and long-term storage of cells
      and tissues ready for use in case of catastrophe. 2. Developing a method for
      estimating the amount of reserved tissue grafts. 3. Solution of logistical
      problems associated with providing supplies for operating theatres treating
      disaster casualties. 4. Organisation of national and international network of
      graft exchange capable of supporting local skin banks in times of need. In
      contrast to the situation in the 1970s and 1980s, nowadays the Czech Republic can
      deliver any required amount of biological covers without having to face
      technological difficulties. The idea of collaborating in the management of a fire
      disaster emerged from experience gained by the authors during the Bashkir
      disaster in 1989, relating particularly to an inadequate reserve stock of skin
      grafts and the impossibility of increasing their production. Intensified demands
      for the safety of grafts and recent experience from the US emphasise the need for
      an immediate conceptual solution concerning production of reserves of biological
      covers that should be ready for transportation to wherever needed. Another urgent
      necessity is the establishment of conditions enabling effective international
      collaboration at a disaster event.

PMID- 12514997
TI  - New type of anaesthesia with sevofluran improves surgical and post-surgical
      course of burns treatment (IGA 6116/2).
AB  - The objectives of this open-perspective clinical study were to test the effect of
      a new type of anaesthesia using sevofluran during surgical treatment of patients
      with burns, and to compare it with that of ketamin, at present the most
      frequently used anaesthetic. The study, conceived as a pilot study, was performed
      on 10 paediatric and 8 adult patients with 2nd degree burns covering between 7%
      and 35% of body surface. Owing to highly significant differences in parameters in
      favour of sevofluran, it was recommended by our ethical committee not to increase
      the number of patients. The parameters considered were ease of induction,
      undesirable effects, span of time before oral administration of liquids. Daily
      uptake of energy was measured for both types of anaesthetics in another group of
      10 patients. In adult patients the two anaesthetics, ketamin versus sevofluran,
      differed in terms of incidence of unrest during surgery (ketamin 50% vs.
      sevofluran 0%, p < 0.05), time between end of surgery and return to full
      consciousness (11.3 min. vs. 2.7 min. p < 0.001), post-surgical inhibition (75%
      vs. 0%, p < 0.01) psychomimetic reactions after surgery (50% vs. 0%, p < 0.05),
      time until first intake of liquids (86.7 min. vs. 8.5 min, p < 0.001), and
      mobilisation (110.8 min. vs. 17 min., p < 0.001). In paedriatic patients,
      differences in speed of onset of anaesthesia (216 sec. vs. 66 sec., p < 0.001)
      and time until first uptake of liquids (75 min. vs. 22 min., p < 0.001) were
      statistically significant. Apart from problems associated with anesthesia,
      another considerable advantage of the new anaesthetic sevofluran was a
      significantly increased uptake of calories after use than was the case after
      ketamin (1645 kJ higher on the average, p < 0.05). Based on these results,
      sevofluran was introduced to burns surgery as a routine anaesthetic.

PMID- 12514998
TI  - [Stab injuries of the heart].
AB  - Stab injuries of the heart belong into the category of fatal injuries. Along with
      the increased crime rate also the number of these injuries increased and they
      must be tackled unexpectedly by the surgeon who frequently lacks specialization
      in cardiosurgery. The authors present the case histories of three patients whom
      they treated successfully in 2001. All there were males, at the time of admission
      to the emergency department with marginal stabilization of the circulation.
      Ultrasound examination of the pericardium revealed in all a haemopericardium with
      amounts from 150 to 300 ml, one man was operated already with symptoms of
      progressing tamponade of the pericardium. During surgical revision in the
      operation theatre always one isolated injury of one of the cardiac departments
      was treated. The postoperative course was uncomplicated and the patients were
      discharged into domiciliary care on the 7th and 8th day after surgery resp.
      Consistent with quoted authors, favourable prognostic factors in penetrating stab
      wounds of the heart include the following: younger age, early transport to the
      emergency centre, presence of cardiac tamponade and early surgical revision by a
      competent surgeon without the necessity of specialization in cardiosurgery. The
      authors emphasize the rule which pushes examination methods into the background:
      stab wound in the cardiac area + unstable circulation = surgical revision.

PMID- 12514999
TI  - [Personal experience with a bilateral approach in the surgical treatment of
      primary hyperparathyroidism. (A group of 222 patients with surgery for primary
      hyperparathyroidism from 1994 to 2000)].
AB  - Surgical treatment offers a definite cure of patients with primary
      hyperparathyroidism. When making the diagnosis of primary hyperparathyroidism the
      success of a surgical solution depends on the experience and judgment of the
      surgeon. Our experience with 222 operations and re-operations convinced us on the
      preference of a bilateral approach, i.e. exploration of both sides of the neck.
      The ectopic localization of the parathyroid glands, the limited possibilities of
      an unequivocal interpretation of the histological examinations but also the
      frequent incidence of thyropathies leads the surgeon, in our opinion, to the
      complete exploration of both sides of the neck within the framework of the
      primary operation for primary hyperparathyroidism. This approach leads most
      probably to the best results. We use an aimed unilateral approach only in old
      patients who are in a very bad condition where we anticipate a benefit from a
      short operation.

PMID- 12515000
TI  - [Importance of peroperative identification and evaluation of sentinel biopsies in
      colorectal carcinoma--review].
AB  - The authors discuss the problem of sentinel biopsy from the aspect of its
      history, they mention its application in solid tumours, describe the technique
      and identification proper of sentinel lymph nodes and their own experience with
      the application of this method in colorectal carcinoma.

PMID- 12515001
TI  - [Lymphatic mapping and sentinel lymph node biopsy in selected carcinomas of the
      digestive tract].
AB  - The current status of lymphatic mapping and sentinel node biopsy in patients with
      selected carcinomas of the digestive tract is described. The possible future use
      of the method in patients with gastric, small bowel and colorectal malignancies
      is considered. Preoperative lymphatic mapping and reliable identification of
      sentinel node (nodes) in patients with gastrointestinal cancers may lead to
      tailored resections or limited surgical procedures. On the other hand, extended
      lymph node dissection may be performed in those patients in whom the sentinel
      node(s) contains tumour cells or in cases where skip lymphatic nodes metastases
      appear. The method offers the opportunity of improving staging (ultrastaging) by
      identification of patients with early dissemination in lymphatic nodes where
      conventional methods are not sensitive enough. These patients should be
      considered for traditional adjuvant treatment or be included in trials with more
      effective adjuvants regimens. Large prospective multicenter studies are needed to
      find out if the sentinel node concept is valid in gastrointestinal cancer. If the
      answer is yes, several basic diagnostic and therapeutic measures may be changed
      in favour of cancer patients.

PMID- 12515002
TI  - ["Nonsurgical" pneumoperitoneum].
AB  - The authors submit case-histories of patients with an X-ray finding of
      pneumoperitoneum on a native X-ray of the abdomen. Air in the abdominal cavity
      was proved in the majority of cases also on laparotomy, however, the source of
      air was not found. The authors mention four cases from their own department. In
      the first female patient with a generalized gynaecological tumour
      pneumoperitoneum was diagnosed repeatedly before surgery. In the second case a
      female patient was involved with an inoperable pancreatic tumour; obstruction of
      the biliary pathways was resolved by an endoscopically inserted stent. In that
      case too the pneumoperitoneum was repeatedly detected before surgery. The third
      patient with a generalized ovarian tumour, acute abdominal pain and
      pneumoperitoneum died on the second day after operation. Similarly as patient 2
      on necropsy thrombosis of the portal vein was found. In the 4th case the finding
      of pneumoperitoneum was made after diagnostic technically difficult gastroscopy.
      This patient was not operated. Patients 1-3 were operated without evidence of
      perforation of the digestive tract. For illustration cases described in the
      literature are quoted. The causes of non-surgical pneumoperitoneum are classified
      according to the anatomical site of development. The author describes the assumed
      mechanisms of development of non-surgical pneumoperitoneum. In the discussion
      aspects are mentioned which decide on conservative or surgical treatment of
      pneumoperitoneum.

PMID- 12515003
TI  - [Primary adenocarcinoma of the duodenum].
AB  - The authors describe a case of 60-year-old man with primary adenocarcinoma of the
      distal duodenum. The first, ex post assumed symptom, was haemorrhage into the
      gastrointestinal tract almost two years before the final diagnostic conclusion.
      The diagnosis was not correctly established even during subsequent examinations
      during progression of the disease and not even during the first surgical
      revision. The reason is, no doubt, the rareness of the diagnosis and the adverse
      site of the tumour. An asset was was enteroscopy, although its conclusion was not
      accurate as regards the site. The tumour was radically removed only during the
      second operation by segmental resection of the distal duodenum with a
      duodenojejunal anastomosis in the region of D2. The patient was then referred to
      the care of an oncologist. The case shows the diagnostic difficulties and the
      unique operation that was performed. Possible success of treatment is always
      conditioned by coordinated gastroenterological, surgical and oncological care.

PMID- 12515004
TI  - [The Lotheissen-McVay operation for inguinal hernia].
AB  - AIM: The authors evaluated the results of operation for inguinal hernia according
      to Lotheissen-McVay in their own group of patients. MATERIAL AND METHOD: During
      the period from July 1996 to October 1998 122 patients were operated by the
      method according to Lotheissen-McVay. The inguinal hernia was operated by this
      method in 120 cases and femoral hernia in 2 cases. RESULTS: There were 2 relapses
      in our group of patients, i.e. 1.64% (2/122). In both cases there was a
      coincidence with secondary healing. CONCLUSION: The operation according to
      Lotheissen-McVay is suitable method for surgical treatment of inguinal hernia.

PMID- 12515005
TI  - [Surgical risk in treatment of a bleeding gastroduodenal ulcer in the era of
      invasive endoscopy].
AB  - OBJECTIVE: Objectivization of the asset of the present therapeutic algorithm in
      patients with haemorrhage from peptic gastroduodenal ulcers using invasive
      endoscopic and surgical haemostasis. METHOD: Comparison of quantitatively and
      qualitatively equivalent groups of 341/318 patients, the first group without
      application of invasive endoscopy, the second one with its application. RESULTS:
      Surgical haemostasis was called for in 12.3/11.6% cases. 92.9/59.5% operations
      were resections and bionomic operations, the mortality of the patients was
      14.3/21.6%, re-operation was necessary in 7.1/13.5% cases. At the time of
      operation 57.1/78.3% patients were a high risk, the length of the "critical"
      interval of haemorrhage in the second group increased by 48.3%. CONCLUSIONS: The
      present accepted procedure of haemostasis is associated with risks of limited
      selection of the optimal method of invasive endoscopy, the protraction of the
      interval of haemorrhage with an adverse rise of the index of the patient's risk,
      inadequate stabilization of the patient during the interval of haemorrhage and
      controversial indication of surgery in case of intractable haemorrhage.

PMID- 12515006
TI  - [Gastrointestinal surgical complications after kidney transplantation].
AB  - BACKGROUND AND OBJECTIVE: Clinical spectrum of gastrointestinal (GI) complication
      in renal transplant recipients ranges from nonspecific signs of abdominal
      discomfort to life-threatening surgical emergencies. The manifestation of such
      complications is modified by antirejection therapy with resulting risk of
      diagnostic and therapeutic error. The present study analyses the incidence of
      serious GI complications after renal transplantation and their treatment.
      METHODS: Retrospective analysis in a university transplant center in years 1988
      2000. There was 239 renal transplants performed in 234 patients (age 42 +/- 14).
      Male to female ratio was 140.99. Polycystic kidney disease patients comprised 9%
      (n = 22). RESULTS: Five serious GI complications resulting in death were recorded
      (2x upper GI bleed, 1x acute pancreatitis, 1x bowel obstruction in sclerotizing
      peritonitis, 1x diffuse purulent peritonitis of unknown origin). There was no
      case of diverticulitis. The average time onset of lethal GI complication was 2.8
      +/- 1.4 years after renal transplantation. There was no statistically significant
      relation to underlying diagnosis of renal failure, warm and cold ischemia time,
      and time elapsed after transplantation. CONCLUSION: GI complications have
      increased incidence in patients after renal transplantation. The incidence of
      complications has no relationship to underlying diagnosis of renal failure, warm
      and cold ischemia time, and time elapsed after transplantation. Patients involved
      in transplant program should be carefully followed and thoroughly examined with
      any new GI symptomatology. Further studies are necessary to evaluate potential of
      pre-transplant screening programs.

PMID- 12515007
TI  - [Fallopian tube torsion in appendicitis--case report].
AB  - The authors report a rare clinical case of coincidence appendicitis and Fallopian
      tube torsion. A 14-years-old girl is presented with acute pelvic pain, dysuria
      and diarrhoea. Acute appendicitis and right side Fallopian tube torsion were
      detected by laparotomy. Symptoms, differential diagnoses, etiology and diagnostic
      procedures are discussed.

PMID- 12515008
TI  - [Principles of surgical treatment of varicose veins with regard to new findings
      on venous hemodynamics].
AB  - Pressure changes occurring during the activity of the calf muscle venous pump are
      the driving force of venous hemodynamics in the lower extremity. An ambulatory
      pressure gradient arises between the veins of the thigh and the lower leg as a
      consequence of pumping up the blood from the deep veins of the lower leg, where
      the venous pressure decreases, into the popliteal and femoral vein, where no
      pressure decrease occurs. Therefore, venous reflux can only take place in an
      incompetent vein connecting the femoral, profunda femoris, popliteal or iliac
      vein with one of the deep veins of the lower leg. Calf perforators represent the
      so called re-entry points and can't become the source of reflux. Venous reflex
      disturbs venous hemodynamics to a various degree dependent on the magnitude of
      reflux volume. When strong enough, it can produce the graviest form of chronic
      venous insufficiency even if localised in superficial veins. The magnitude of
      reflux volume, not the localisation of reflux in deep or superficial veins is the
      most important hemodynamic factor causing venous disturbance. The goal of
      varicose vein surgery is to remove reflux and visible varicose veins with the aim
      to achieve the most favorable hemodynamic and cosmetic results. Crossectomy is a
      very important step, because it is able to repair even the most pronounced
      hemodynamic disorder and restore normal hemodynamic conditions. If stripping of
      the incompetent saphenous trunk on the thigh is not performed in addition to
      crossectomy, the saphenous trunk continues to be patent and incompetent after
      surgery in most patients and provokes recurrent reflux. But nor can crossectomy
      combined with stripping avert the risk of recurrence definitively, because
      varicose veins are a dynamic disease with distinct tendency to recurrence.
      Correctly performed operation can reduce the recurrence rate and postpone its
      occurrence. A hemodynamic factor--the ambulatory pressure gradient--triggers
      probably the process leading to recurrence. When varicose veins recur, the
      recurrent reflux volume remains significantly lower for many years of follow-up
      as compared with the situation before surgery. External banding of incompetent
      valve in the long saphenous vein and the CHIVA-method are less efficient in
      comparison with standard surgery (crossectomy plus stripping). Sclerotherapy is a
      useful supplement to surgery during follow-up, as it is able to improve
      significantly the hemodynamic situation. This improvement is only transitory, but
      sclerotherapy can be repeated and the improvement re-established, if necessary,
      during follow-up.

PMID- 12515009
TI  - [Torsion of the spleen--an unusual cause of sudden acute abdomen].
AB  - Torsion of a wandering spleen is rare and has been diagnosed in about 0.2%-0.3%
      of a large group of patients who required splenectomy. Abnormalities in the
      ligamentous structures that fix the spleen are thought to be responsible for its
      abnormal position and for its torsion. Patients may present with various symptoms
      ranging from mild intermittent abdominal pain to an acute abdomen. Computed
      tomography leads to correct diagnosis.

PMID- 12515010
TI  - [Bowel injuries after blunt abdominal traumas].
AB  - Authors present 28 cases of bowel injuries after blunt abdominal trauma. Patients
      were from 14 to 71 years of age, 18 (64%) men and 10 (36%) women. The most common
      cause for the trauma was the car accident--in 18 cases. In the rest 10 the trauma
      was result of household activities. The small bowel was injured in 16 patients,
      the large bowel in 9 and in 3--the duodenum. In 15 cases the trauma was only
      abdominal and in the rest 13 it was accompanied by other traumas. Three of the 28
      patients reported herein died.

PMID- 12515011
TI  - [Surgical treatment of complicated gastrointestinal forms of non-Hodgkin
      lymphomas].
AB  - Authors represent their experience in surgical treatment of gastrointestinal
      forms of No-Hodgkin's lymphomas (NHL) combined with adjuvant therapy. We also
      represent an Ann Arbor Staging System and an Updated Kiel Classification. From
      1991 to 2001 we analyzed 39 patients with different localization of gastro
      intestinal NHL's lymphomas. In this aspect more common are stomach's lymphomas-
      27 patients (71%); small bowel's lymphomas--3 patients (8%); more uncommon are
      the localizations in colon--3 patients (8%), predominantly in caecum and right
      colon; rectum--3 patients (5%). Add to thus we described one mechanical icterus
      caused lymphoma, one multi-lobular spleen lymphoma and one case of anterior
      abdominal wall lymphoma. All patients underwent surgery. Eight of them were
      operated as an emergency cases. Operative treatment of NHL isn't radical but in
      combination with adjuvant therapy can be life saving event in complicated forms.

PMID- 12515012
TI  - [Hepatic echinococcosis: radical or conservative surgical treatment].
AB  - Hydatid liver disease remains an actual medical and social problem for Bulgaria
      as an endemic region. Because of the lackage of medicines with satisfactory
      therapeutic effect the surgical treatment is still the treatment of primary
      importance. AIM: The aim of this study was too check the correctness of the
      following hypothesis: "Radical surgical procedures on hydatid liver disease have
      lower rates of morbidity and mortality compared to conservative ones". MATERIAL
      AND METHODS: In order to achieve the above mentioned aim we analysed the results
      of 361 patients with hydatid liver disease (267 (74%) of whom retrospectively and
      94 (26%) prospectively), treated at the Clinic of General, Liver and Pancreatic
      Surgery during the period 1st, Jan., 1985-1st, Jan., 2001. The patients were
      divided in two main groups: 102 (28.25%) of them received radical surgical
      procedures and 250 (69.25%)--conservative ones. Nine of the patients (2.50%) had
      multiple echinococcal cysts and received surgical procedures of both types.
      That's why the results of those patients did not correspond to the aim of the
      study and they were not included in it. The analysis consisted of a comparison
      between the two main groups according to several criteria: sex, age, location and
      average size of the cysts, postoperative complications, reoperations, mean
      postoperative stay at hospital and mortality rate. RESULTS: There was a
      prevalence of the female in the ratio male/female in the group of patients who
      received a radical procedure. The location of echinococcal cysts in the left
      hepatic lobe was found to be more frequent. In the group of radical surgical
      operations the postoperative morbidity and mortality rates were lower and the
      postoperative stay at hospital was shorter, compared to the group of conservative
      procedures. CONCLUSION: Radical surgical procedures showed better postoperative
      results. But those procedures had to be performed only on patients who had
      certain indications and according to criteria described in surgical literature.
      The proper surgical equipment and well experienced surgical team were the other
      important conditions for good outcome.

PMID- 12515013
TI  - [Central segments resections in primary liver neoplasms--three clinical cases].
AB  - BACKGROUND/AIMS: The resections of the central paramedial hepatic sectors are
      most rarely reported due to their technical complexity. We present three cases in
      which we carried out this rare operative intervention for occasion of primary
      hepatic neoplasm in the central hepatic segments. MATERIAL AND METHODS: In three
      cases (two of primary hepatic cancer and one of sarcoma) we carried out resection
      of the central segments in the following steps: mobilization of the liver,
      subhepatic approach to the inferior v. cava, preparation for vascular isolation
      of the liver by Pringle's maneuver, dissection of the biliary, arterial and
      venous vessels in the hepatic hilus, intraoperative assessment of the involvement
      of these structures in the neoplastic process and subsequent hepatic resection.
      RESULTS: For a period of 5 to 24 months of follow up we have not established a
      relapse of the disease in the cases ascribed. CONCLUSION: The outcome of the
      hepatic resections strongly depends from the various factors including accurate
      preoperative diagnosis, the assessment of the resection volume according to the
      involvement of the hepatic vessels in the neoplastic process. Hepatic resection
      can be performed with the same degree of confidence and similar low morbidity as
      any other major surgical procedure.

PMID- 12515014
TI  - [Anterior rectal resection--early postoperative results].
AB  - BACKGROUND: The development of the mechanic staplers gave the opportunity to
      perform sphincter-saving operations in patients with middle and low rectal
      carcinoma. It has been gained experience in performing this operation as the
      anastomosis was sewed in both ways--manually and mechanically. PURPOSE: The
      purpose of this retrospective research is to analyse the early postoperative
      results after anterior rectal resection with manually and mechanically made
      anastomosis. MATERIAL AND METHODS: For the period 01.01.1995-01.012000 in the
      DEPARTMENT OF GENERAL, LIVER AND PANCREATIC SURGERY, 69 patients with rectal
      carcinoma underwent the operation anterior rectal resection. In 60 cases (89.96%)
      the anastomosis was made manually and in 9 cases (13.04)--with mechanical
      staplers. Both patient groups are studied and classified by sex, age, tumor
      localisation, type of anastomosis, early postoperative results. RESULTS: From the
      group with manually sewn anastomosis 6/10%/ of the patients had complications in
      the early postoperative period, one of them terminated (1.7%). From the second
      group 3 (33.3%) of the patients had complications in the early postoperative
      period. The average postoperative hospitalisation was 13.5 vs. 19.2 days.
      CONCLUSION: The results achieved in anterior rectal resection depend on a complex
      of factors among which more important is the early diagnosis of the disease and
      the skills of the surgeon in coloproctology.

PMID- 12515015
TI  - [Behaviour of patients with inflammatory intracranial complications of otogenic
      origin].
AB  - The authors have the aim to discuss their experience in the field of treatment of
      otogenic intracranial complications results of inflammatory process. A short
      reference of the spread of this kind of pathology is made. The up-to-date methods
      for diagnostics, behaviour, conservative and surgery treatment of these patients
      are examined. A case is represented as an illustration, that regardless of the
      big progress in the medical knowledge and the opportunities of the surgery
      technique nowadays, these complications continue to be a serious problem in the
      otorhinolaryngology and enforced close collaboration. The publication is a
      teamwork of otorhinolaryngologists and neurosurgeons.

PMID- 12515016
TI  - [Reconstruction of auricular skeleton with maternal ear cartilage in patient with
      microtia].
AB  - The proposed operative technique with maternal auricular cartilage ear-donor) is
      modification of the method of M. Madzharov et al., for total and partial
      reconstruction of the auricle. The method includes the use of allogenic auricular
      cartilage and autogenic perichondrium (rib of auricular), attached to the
      cartilage with autogenic fibrin glue and/or sutured by nylon. The method is
      applied to 18 years old female patient with bilateral microtia III gr., for
      reconstruction of the left year. 2 years later, satisfying cosmetic result was
      encountered on the operated left ear and ear-donor. Briefly summarizing,
      auriculoplasty with maternal auricular cartilage is reliable method, especially
      in cases when cartilage of the ear-donor is strictly subperichondrially dissected
      and covered with autogenic rib of auricular perichondrium.

PMID- 12515017
TI  - [Operation on maxillary sinus using the osteoplastic graft].
AB  - The authors share their experience in the operation of the maxillary sinuses by
      using osteoplastic graft. This technique allows saving or reconstructing of the
      front sinus wall. It makes possible isolation of soft tissues from the upper
      maxilla and preventing infection and other complications. We didn't find any
      pathological changes in the 2 year follow-up period. We recommend and find this
      technique reliable.

PMID- 12515018
TI  - [Diagnostic puncture and puncture treatment of liver echinococcosis--"yes" or
      "no"].
AB  - The authors present as problematic and debatable the article about the diagnostic
      punction and punction treatment of the liver echinococcosis. Of many years
      scientific disputation about this problem exist. The risks of per cutaneum
      punction leads to many serious complications. This assess the revaluation of this
      method which must apply only in very limited evidence--small surface cysts
      without additional cysts and for diagnostic plan must be abandon.

PMID- 12515019
TI  - [Hepatorenal syndrome].
AB  - Functional renal disorders commonly complicate cirrhosis and ascits, and in its
      terminal stage is known as hepatorenal syndrome (HRS). HRS is defined as the
      development of renal failure in patients with advanced liver failure (acute or
      chronic) in the absence of other identifiable causes of renal pathology. It is a
      syndrome characterized by oliguria, severe renal sodium retention, circulatory
      instability with marked systemic arterial vasodilatation and activation
      vasoactive systems. Signs of renal functional impairment may be observed in more
      than 30% of patients with cirrhosis and ascites, but only about 5% showed typical
      signs of HRS. In patients with decompensated cirrhosis, HRS has been found in
      about 18% after 1 year and in 40% after 5 years of follow up. In this survey are
      showed the diagnostic criteria for HRS as set out by the International Ascites
      Club. According to this criteria HRS was considered present when serum creatinine
      was > 1.5 mg/dl and creatinine clearance < 40 ml/min. Several therapeutic
      approaches have been proposed to modify the altered systematic and renal
      hemodynamics occurring during HRS. Administration of plasma expanders or
      vasoconstricting drugs, peritoneovenous shunting, portosystemic shunts and
      transjugular intrahepatic portosystemic shunts have been used to reverse
      peripheral vasodilatation and improve vascular underfilling. Renal vasodilatators
      and prostaglandins have been administered to reduce renal vasoconstriction.
      Theoretically the ideal treatment for patients with HRS is liver transplantation.
      The prognosis for HRS is poor and treatment almost always unsatisfactory when
      liver transplantation is excluded. The best treatment of HRS is preventing
      precipitating factors.

PMID- 12515020
TI  - [Two methods of plastic reconstruction of extensive defects of the chest wall
      (experimental study)].
AB  - The authors examine results from the experimental using two new methods for
      surgical reconstruction of broad defects of the chest wall. Our study was applied
      to 18 dogs separated in two series. In the first group of 8 dogs we used bone
      muscle lambo for plastic reconstruction formed from the scapula and m.serratus
      anterior. This autotransplantation tissue was fixed for the neighbouring ribs
      limiting the defect of the chest wall. A good hermetisation of the pleural cavity
      and stabilisation of the chest wall was achieved. In the second group of 10 dogs
      the chest wall defects was closed with special antimicrobal chest prosthesis. It
      is built up by synthetic net and synthetic ribs. The antimicrobic qualities are
      being preserved for a continuous period of time. Histological the animals from
      the first group show the creation of a stabile fibrosis-bone-muscle laver which
      creates stability and hermetically of the chest cell. The synthetical ribs of the
      animals from the second group are tightly embraced by cellular tissue that passes
      through the openings of the ribs. The clinical observations of this methods are
      an object of another report of ours.

PMID- 12515021
TI  - [A case of surgically removed retroperitoneal rhabdomyosarcoma in a child
      requiring vascular reconstruction].
AB  - Retroperitoneal tumors engaging large vessels require vascular reconstruction
      when surgically removed. We present a case of retroperitoneal rhabdomiosarcoma in
      a child, which required inferior vena cava (IVC) grafting, creating a new
      bifurcation of IVC, and an A-V fistula between greater saphenous vein and femoral
      artery as well as grafting of right common iliac artery.

PMID- 12515022
TI  - [A case report of vascular tumors of the spleen].
AB  - The authors present literature data on the problem of vascular tumours of the
      spleen and describe clinically and morphologically primary epitheloid
      hemangioendothelioma. They paid attention on detailed characteristic of the
      tumours and differential diagnosis of with vascular neoplasms of the spleen.

PMID- 12515023
TI  - [Surgical tactic in a severe form of Crohn's disease complicated by ileus and
      cachexia].

PMID- 12515024
TI  - [A case of Non-Hodgkin malignant lymphoma with cervical and mediastinal lymph
      nodes combined with microcarcinoma of the thyroid gland].

PMID- 12515025
TI  - [Results of surgical treatment of primary liver cancer].
AB  - Using a single institution experience, the authors examine hepatic resections in
      treatment of primary liver cancer (PLC), the postoperative complications and
      mortality. Seventy-three patients were operated on between January 1991 and
      December 2000 and identified in a retrospective database. They were 53 men and 20
      women of mean age 54.6 (from 1 to 78 years). Of the 73 operated patients with
      PLC, 53 underwent hepatic resection. Two patients had PLC at stage II, 43--stage
      III, 8--stage IV. 25 (34%) patients had underlying cirrhosis: 14--Child A and 11-
      Child B. 34 patients underwent major resections and 19--minor resections. 7
      patients (13.2%) died of the hepatic resection--by the 30-th day. Mortality among
      cirrhotic patients was 25% (4 patients). 16 patients had postoperative
      complications. 6 patients developed liver failure. Hepatic resection is a basic
      method in treatment of the PLC. The presence of cirrhosis, especially Child B,
      increases surgical morbidity and mortality.

PMID- 12515026
TI  - [Hepatic resections for hepatocellular carcinoma and cirrhosis].
AB  - Liver resection in a patient with cirrhosis carries increased risk. The purposes
      of this study were to review the results of cirrhotic liver resection in the past
      decade and to propose strategies for low morbidity and mortality. From January
      1991 to December 2000 73 patients with primary liver cancer (PLC) were operated
      and identified in a retrospective database. Twenty five (34%) patients had
      underlying cirrhosis: 14--Child A and 11--Child B. There were 18 male and 7
      female with mean age 60.9 +/- 9.2 (from 44 to 78). There were 16 (64%)
      resections: 11--stage Child A and 5--stage Child B. Major resections were 7 and
      minor--9. Eight patients received hemotransfusion--mean 939.13 ml (370-2000 ml).
      Four patients (25%) died of the hepatic resection--by the 30-th day. Seven
      patients had postoperative complications. 4 patients developed liver failure.
      Major resections had 42.86% mortality, minor resections--11.11%. Hepatic
      resection is potentially curative therapy for HCC and cirrhosis especially in
      Child A. Child B produce high rate of postoperative morbidity and mortality.

PMID- 12515027
TI  - [Classifications and prognosis of hepatocellular carcinoma].
AB  - In this study are included 78 patients with hepatocellular carcinoma (HCC). In 22
      the diagnosis is verified pathologically (obduction), while in the other patients
      the diagnosis is made by laparoscopy, laparoscopical ultrasonography and
      morphological verification (through FNAB cytology and/or histology). In 69.2% HCC
      is associated with cirrhosis. The prognosis of HCC associated with cirrhosis is
      evaluated through the classification of S. Chevret et all., and is compared to
      the Child-Pugh scoring system. 38.9% of patients in Chevret's class C score are
      in class B in the Child-Pugh score, while 25.9% of patients are in class C in
      both classifications, but Child-Pugh's class C patients are most often in B-C
      transition. It might be assumed that the prognosis of HCC depends more on the
      tumor prognosis than on the prognosis of the liver cirrhosis itself. Every
      classification which does not take in to account the liver function (like TNM
      system) and the whole characteristics of the tumor, would be incomplete, in some
      extent, in the prognosis of HCC with cirrhosis. In HCC without cirrhosis, the
      BCLC classification reflects both the liver function and the tumor
      characteristics. In BCLC class A patients hepatic resection or transplantation is
      recommended but hyperbilirubinemia and ascites, which might be seen in A3 and A4
      classes contraindicate resection of the liver. All scoring systems define lower
      HCC stage than it is really found (personal and reference data), so there are no
      arguments to take classification scores as absolute treatment decision making
      rules.

PMID- 12515028
TI  - [One-stage operation for multi-organ echinococcosis (bilateral pulmonary, hepatic
      and splenic) by sterno-laparotomy].
AB  - Between 1990 and 2001 in Thoracic Surgery Department at SHATPD "Saint Sophia"-
      Sofia a total of 821 patients with pulmonary hydatidosis were operated on. In 5
      (0.6%) of them the cysts were situated in the both lungs, lever and spleen. For
      the first time in the surgical practice a sterno-laparotomy were carried out for
      one-stage cysts' removal in this multi-organ localization. The stages of this
      approach as well as the indications and contraindications for its applications
      are described in detail.

PMID- 12515029
TI  - [Modified method of Sugiura-Futagawa for surgical treatment in patients with
      portal hypertension and esophageal varices].
AB  - BACKGROUND: The esophageal transection and devascularization (Sugiura-Futagawa's
      operation) is the most frequently used ablative procedure in Japan for the
      treatment of patients with portal hypertension (PH) and esophageal varices (EV).
      Recently many authors, who are followers of this method, try to find an
      alternative one, aiming to shorten the skin-to-skin time and achieve better early
      and late results. AIM: To study the postoperative results of our modification of
      the original Sugiura-Futagawa's method and to conclude whether it is good and
      reliable or not. MATERIAL AND METHODS: From Jan. 1988 till Apr. 2001 we operated
      25 patients with liver cirrhosis, PH and previous hemorrhage from EV, of whom 12
      were male (48%) and 13--female (52%). Age of the patients--26-67 years. The
      ethiology of cirrhosis was alcoholic in 8 cases (32%) and post viral hepatitis-
      in 17 cases (68%). All our patients belonged to Child-Pugh's group A. The
      operative technique of our modification is described--transabdominal esophageal
      devascularisation, deconnection and reanastomosis. RESULTS: The early
      postoperative mortality rate after our modification of the Sugiura-Futagawa's
      method was 12% (in 3 cases). Death cause--fulminant hepatic failure with hepato
      renal syndrome (in all three cases). The mortality rate was also 12% but no one
      of the complications was life threatening or an indication for reoperation. The 5
      year survival rate accounted 78%, recurrent esophageal bleeding--7.14% and late
      hepatal encephalopathy--also 7.14% of the followed patients. DISCUSSION: The
      surgical treatment is of main importance for better survival in cases of PH and
      previously bled EV. A comparison between the results of other authors and our
      results is made. CONCLUSION: The proposed by us transabdominal esophageal
      devascularisation, deconnection and reanastomosis as a modification of the
      Sugiura-Futagawa's procedure is easy fro the technical point of view and leads to
      good results.

PMID- 12515030
TI  - [Surgical treatment of chronic nonspecific empyemas].
AB  - Approximately 4% to 20% of all acute empyema turn into chronic empyema despite
      the up-to-date complex treatment. The authors report their results of the
      surgical treatment of 38 patients with chronic nontuberculous empyema within a 5
      years period. The age of the patients range from 18 to 72 years and they include
      26 men and 12 women. Twenty eight were treated by thoracotomy and decortication,
      7 underwent video-assisted thoracoscopy and decortication, and 3 thoracoplasty.
      In one of the patients a latissimus dorsi muscle flap was used.

PMID- 12515031
TI  - [Surgical treatment of post-traumatic intrapulmonary haematomas].
AB  - In a 14-year period 18 patients with post-traumatic intrapulmonary haematomas
      (PIH) were diagnosed and treated in our departments. There were 14 men and 4
      woman with mean age 42.1 year. The mean diameter of PIH was 7.5 cm and they were
      localized mainly in the left lower lobe. Three of the patients were successfully
      treated with conservative antibiotic and mucolytic therapy. The remaining 15
      patients (83%) were operated on: lobectomy (7), segmental resection (2),
      extirpation with partial resection of the fibrous capsule and capitonnage (4) and
      total extirpation with fibrous capsule removal (2). Indications for surgery were
      as follows: infection, haemoptysis and suspicions of malignant lesion. The early
      and late results are excellent. We recommend the surgical approach to PIH as a
      safe and effective treatment.

PMID- 12515032
TI  - [Major respiratory tract traumas].
AB  - Between 1988 and 2000 a total of 33 patients with traumatic tracheobronchial
      lesions were diagnosed and treated. The trauma was penetrating in 7 (stab and gun
      shot), blunt in 10 (car accidents, compression and falling from heights) and
      iatrogenic in 16 of them (postintubational--15, after foreign body extraction-
      1). The main clinical and radiological features were subcutaneous emphysema,
      hemoptysis, respiratory insufficiency, pneumomediastinum and pneumothorax. The
      diagnosis was confirmed in all patients by early fiberoptic bronchoscopy. "Watch
      and see" tactics with massive antibiotics therapy was followed in 4 (12%)
      patients. A surgical treatment was carried out in 29 (88%) patients as follows:
      simple repair--19 (58%), left pneumonectomy--2 (6%), tracheal resection and
      anastomosis "end to end"--2 (6%), tracheostomy--1 (3%), thoracocenthesis and
      drainage--3 (9%) and cervical mediastinotomy--2 (6%). The operative mortality was
      9%. The cause of death in these 3 patients were associated brain and spinal cord
      injuries. In the rest of patients the early and long-term postoperative results
      were considered very good.

PMID- 12515033
TI  - [Active specific immune therapy of prostate gland cancer].

PMID- 12515034
TI  - [Mesenteric-inferior-renal shunt--alternative of proximal and distal spleen-renal
      shunt for surgical treatment of portal hypertension].
AB  - Surgical operations are important for the prevention of recurrent bleeding and
      better survival rates in patients with portal hypertension and previous
      haemorrhage from esophageal varices, stopped by conservative treatment. Spleno
      renal shunts are among the most frequently used procedures in these cases.
      Sometimes the proximal spleno-renal shutting operation of Linton or the distal
      one of Warren may be impossible from the technical point of view due to anomalies
      or varieties of the lienal vein. This makes it necessary to look for an
      alternative decision. This case report is about a 33-year old man indicated for
      surgical treatment because of portal hypertension, caused by prehepatic portal
      vein obstruction and esophageal varices with previous bleeding. Performing
      Linton's or Warren's procedure was not the proper decision. That's why we made a
      shunt between the inferior mesenteric vein and the left renal vein. The surgical
      technique and the postoperative results are described and discussed.

PMID- 12515035
TI  - [Hemobilia caused by gallbladder's polyps in liver cirrhosis].
AB  - Extremely unusual cause of hemobilia from polypus of the Gallbladder in 29 years
      old patient with liver cirrhosis is reported. The patient died with clinical
      features of hepatic encephalopathy. The olygosympthomatic clinical course is the
      reason for unrecognized hemobilia. The ultrasonographic diagnosis was
      "cholelithiasis" instead of gallbladder's polypus and endoscopy established large
      ulcer in the duodenum. The role of hemorrhagic diathesis in chronic liver disease
      is discussed. As is the extent of liver cirrhosis, cholestasis and hepatic
      encephalopathy deterioration caused by bleeding. Whether timely cholecystectomy
      could change the course and prognosis of chronic liver disease is also discussed.

PMID- 12515036
TI  - [Acute surgical abdomen in idiopathic haemochromatosis].
AB  - The acute abdomen (AA) is a typical but very rare complication of idiopatic
      haemochromatosis (IH). The possible mechanisms are not sufficiently clarified. We
      report a case with IH who died with clinical features of (AA) 20 hours after
      gastroscopy was performed. The histological examination established nonspecific
      damage of visceral peritoneum and ascites. Fulminant form of spontaneous
      bacterial peritonitis (SBP) as a reason of death is discussed, nevertheless
      endoscopic esophageal varices sclerotherapy was not performed. The role of
      pulmonary infection and intestinal bacterial overgrowth with possible bacterial
      translocation in mesenterial lymph nodes, ascitic fluid, and blood is also
      discussed. The source of infection is usually unknown. The iron is important
      factor for bacterial growth. The pluriglandular deposition of iron including the
      suprarenal glands is precondition to development of collapse. The possible
      pathogenesis of SBP in IH is discussed. It is important to mention that unlike
      SBP the clinical course of IH AA might appear which does not necessary require
      surgical management.

PMID- 12515037
TI  - [The overworked physician. II].
AB  - Medical doctor is exposed to various types of professional stress. One of the
      risk factors is the lack of awareness of the fact that patients frequently do not
      do what is necessary, and that possibilities of therapy are limited. Another risk
      factor is a deep identification with patient. In relation to colleagues, the risk
      factor represents the low ability to communicated, and resulting feeling of
      isolation. The higher professional gratification was derived from the sense of
      being needfull and from successful resolution of difficult cases. Majority of
      studies came to the conclusion that the effective prevention of health troubles
      is the balanced life-style and the possibility to discuss with colleagues both
      the professional difficulties and possible conflicts with patients as well as
      personal worries. Essential is also an emphatic though pragmatic relation to
      patient and to the possibilities of therapy. Many medical doctors referred the
      necessity of developing a personal and professional philosophy. The elementary
      example is the appropriate hierarchy of values and priorities, organisation of
      time and solution of conflicts of interests.

PMID- 12515038
TI  - [Enzyme inhibition in the drug therapy of benign prostatic hyperplasia].
AB  - Enzyme inhibition belongs to common mechanisms of drug action and enzymes of
      hormone metabolism belong to targets in the treatment of benign prostatic
      hyperplasia. Transformation of testosterone to 5 alpha-dihydrotestosterone is
      catalyzed by cholestenone-5 alpha-reductase (EC 1.3.1.22, 5 alpha-reductase).
      Different effects of dihydrotestosterone and testosterone represent a rational
      basis for pharmacotherapy by 5 alpha-reductase inhibition. The enzyme is active
      in the prostate and other organs and tissues, with different distribution of at
      least two 5 alpha-reductase isoenzymes. Beside this, progesterone-5 alpha
      reductase (EC 1.3.1.30) as another enzyme with 5 alpha-reductase activity is
      present in human tissues including the prostate. The existence of several 5 alpha
      reductase activities gives bright possibilities of 5 alpha-reductase inhibition.
      Basic 5 alpha-reductase inhibitors are synthetic steroid (e.g. finasteride-
      Proscar). Various mechanisms of their effect (classical reversible competitive
      inhibition, mechanism-based "suicide" inhibitors, tightly bound irreversible
      inhibitors...) represent different pharmacokinetic patterns, too. Non-steroidal 5
      alpha-reductase inhibitors (e.g. polyunsaturated fatty acids) are effective
      components of several phytopharmaceuticals. They receive attention due to their
      complexity and low hazards. Extracts of Serenoa repens seeds (Permixon, Capistan
      in the Czech Republic), of Pygeum africanum, of Urtica radicis roots (Urtica,
      Urtiron) or catequine structures from the green tea belong to this group. Beside
      androgens, participation of estrogens in the origin and development of benign
      prostatic hyperplasia is probable. Inhibition of the "aromatase" complex, which
      catalyzes transformation of androgens to estrogens, may contribute to the
      complexity of phytotherapeutic effects.

PMID- 12515039
TI  - [A new missense mutation of 574C>T in the SURF1 gene--biochemical and molecular
      genetic study in seven children with Leigh syndrome].
AB  - BACKGROUND: Leigh disease, subacute necrotizing encephalopathy, is a serious
      mitochondrial disorder of energy-providing metabolism. Clinical presentation
      usually starts in infancy as a progressive neurodegenerative disorder with
      retardation and regression of psychomotor development. The most common form of
      the disease is associated with deficiency of the cytochrome c oxidase (COX) due
      to SURF1 gene mutations. SURF1 encodes an inner mitochondrial membrane protein
      involved in the biogenesis and assembly of COX complex. METHODS AND RESULTS: The
      activities of mitochondrial respiratory chain complexes were determined
      spectrophotometrically in isolated lymphocytes, platelets, muscle mitochondria
      and cultured fibroblasts. Generalised decrease of COX activity was found in 7
      children with typical symptoms of Leigh disease. Two-dimensional electrophoresis
      of mitochondrial proteins showed altered assembly pattern of COX. As demonstrated
      by Western blot analysis of mitochondria or mitoplasts with anti-hSurf1
      antibodies (gift from Dr. E. A. Shoubridge), the Surf1 protein was absent in all
      5 investigated patients. Molecular analyses in the 7 patients revealed the
      presence of mutations in the SURF1 gene--six patients harboured previously
      described SURF1 mutations, a new mutation 574C > T was found in one patient.
      CONCLUSIONS: The co-operation among the patient's families, clinicians and
      specialised laboratories is essential for the diagnostic of mitochondrial
      disorders. The treatment of Leigh syndrome is only symptomatic and the prognosis
      of the disease is unfavourable. The diagnostics on biochemical and molecular
      level is necessary for genetic counselling and prenatal diagnosis in affected
      families.

PMID- 12515040
TI  - [Molecular analysis of Wilson disease].
AB  - BACKGROUND: Wilson disease is an autosomal recessive disorder, characterized by
      cooper accumulation and intoxication of the organism. Molecular basis of the
      disease represent mutations in the gene for the copper-transporting ATPase
      (ATP7B). METHODS AND RESULTS: The submitted paper deals with results of molecular
      genetic examination in 130 unrelated families in which Wilson disease was
      diagnosed. By denaturing gradient gel electrophoresis (DGGE), the exons with
      abnormal sequences were detected. Followed by sequencing, 17 causal mutations and
      9 silent polymorphism were found. Five novel mutations were detected. After
      analysis of 260 mutant alleles, 214 (82.3%) were identified. The most frequent
      mutation, H1069Q, occurred in our population with the frequency of 65.8%.
      Incidence of other mutations, however, did not exceed 5%. CONCLUSIONS: DNA
      analysis of the Wilson disease offers prompt and reliable results in affected
      families. It can help to identify asymptomatic and heterozygote siblings at
      genetic counselling.

PMID- 12515041
TI  - [Autoimmune enteropathy with onset in early infancy: clinico-morphologic and
      immunologic manifestations].
AB  - This paper describes a severely affected male infant with serious protracted
      diarrhoea caused by a rare autoimmune enteropathy. The disease began at 6 weeks
      of age of the child and it was associated with small bowel villous atrophy and
      the presence of circulating antienterocyte antibodies. The child was treated with
      steroids and with parenteral and special enteral nutrition. The patient showed
      clinical improvement as documented by decreased stool output and possibility to
      terminate the parenteral nutrition. The small biopsy samples showed a return to
      normal. Antienterocyte antibodies were negative after the treatment. The patient
      has been followed up for at least 18 months and was in a clinical remission. We
      recommend that autoantibodies tests should be performed in all infants with
      unexplained protracted diarrhoea. The use of potent immunosuppressive drugs and
      the increasing experience with parenteral and enteral nutrition can improve the
      perspective of these previously fatal disorders.

PMID- 12515042
TI  - [History of Williams syndrome].
AB  - History of the Williams syndrome (WS) represents a process of detailed analysis
      of phenotypic markers and of attempts to reveal their origin. This demanding
      tasks have brought many valuable findings, which were employed in different
      fields of medicine, namely in cardiology, metabolism, genetics, psychology and
      cognitive neurosciences. Discovery of the genetic basis of the disease closed the
      first period of the syndrome analysis. Genetic studies have been proceeding and
      WS can be taken as a model syndrome for the behavioral genes identification.
      Similarly the description of the pathogenesis of vascular anomalles represents
      the key for understanding of the pathogenesis of other, more common vascular
      diseases. The article brings the review of the history of the WS.

PMID- 12515043
TI  - Prophylaxis against anthrax.
AB  - The paper presents fundamental knowledge concerning Bacillus anthracis and its
      potential terrorist misuse. The basic clinical forms are resumed with emphasis on
      inhalation infection from inspiration of B. anthracis spores. The AVA vaccine
      licensed in the United States, primary vaccination, protective efficacy of the
      vaccine, and adverse events are characterised. Stress is laid on pre-exposure and
      post-exposure prophylaxis of anthrax.

PMID- 12515044
TI  - In vitro glycation of aminotransferases: a process closely depending on the
      employed experimental conditions.
AB  - The aim of the present study is to investigate the influence of various
      experimental conditions, i.e., two different concentrations of D-fructose as a
      rapidly glycating substance and three incubation temperatures, on the glycation
      reaction of alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate
      aminotransferase (AST, EC 2.6.1.1) expressed by decreasing catalytic activities
      of the enzymes during a 56 day in vitro incubation period. D-fructose in the
      concentration of 50 mmol/l did not inhibit the catalytic activity of either
      enzyme at 4 degrees C, partially inhibited AST activity in samples incubated at
      25 degrees C (to 40% of the initial activity), and completely inhibited this
      enzyme at 37 degrees C at the end of the incubation period. In the presence of
      the same concentration of D-fructose, ALT showed no catalytic activity after 35
      days at 25 degrees C or after 10 days at 37 degrees C. In 500 mmol/l D-fructose,
      complete AST inhibition was observed after 35 days (25 degrees C) or 20 days (37
      degrees C), and no ALT activity was found on day 20 at either 25 degrees C or 37
      degrees C. Taking into account the highest possible stability of enzymes, we
      suppose that a three-week observation of their residual catalytic activity in the
      presence of 50 mmol/l D-fructose at the temperature of 25 degrees C seems to be
      the most prospective experimental design for future glycation studies with
      aminotransferases under the influences of drugs.

PMID- 12515045
TI  - Comparison of enoximone, amrinone, or levosimendan enriched St. Thomas' hospital
      cardioplegic solutions used for myocardial preservation in isolated guinea pig
      hearts.
AB  - Myocardial contractile function after cardioplegic arrest is often depressed and
      an ideal cardioplegic solution has not been developed yet. The aim of this study
      was to assess the efficacy of phosphodiesterase III inhibitors, amrinone and
      enoximone, and levosimendan, a novel Ca2+ sensitizing agent, on recovery of
      hearts after normothermic cardioplegic arrest when added to the St. Thomas'
      hospital cardioplegic solution. In the control group, isolated guinea pig hearts
      were perfused in Langendorff apparatus and arrested with standard St. Thomas'
      solution. In other groups, amrinone (10(-5) mol.L-1), levosimendan (10(-5) mol.L
      1), or enoximone (10(-4) mol.L-1) were added to the cardioplegic solution. In all
      hearts, intraventricular pressure, +dp/dtmax, -dp/dtmax, area under pressure-time
      curve, heart rate, coronary flow, lactate dehydrogenase and creatine kinase
      enzyme leakage, and oxygen consumption were measured. In the enoximone group,
      contractility force and +dp/dtmax, were found to be significantly high in the
      reperfusion and inotropic periods in comparison with other groups (p < 0.05). 
      dp/dtmax and area under contractility-time curve values were significantly high
      in inotropic period in enoximone group (p < 0.05). No statistically significant
      difference was noted in other groups. Cardioplegic solution enrichment with
      enoximone augmented mechanic functions in reperfusion period. No positive effect
      of amrinone or levosimendan was observed in this study.

PMID- 12515046
TI  - Effect of sodium 2,3-dimercaptopropane-1-sulphonate (DMPS) on chronic
      daunorubicin toxicity in rabbits: comparison with dexrazoxane.
AB  - A possible protective action of DMPS (a dithiol chelating agent) against chronic
      daunorubicin toxicity in rabbits in comparison with dexrazoxane was investigated.
      The rabbits were divided into five groups: control (saline, 1 ml/kg i.v.),
      daunorubicin (3 mg/kg i.v.), DMPS (50 mg/kg i.v.); the remaining two groups were
      pre-treated either with dexrazoxane (60 mg/kg i.p.) or DMPS (50 mg/kg i.v.) 30
      min before administration of daunorubicin (3 mg/kg i.v.). Drugs were given once a
      week for 10 weeks. Routine biochemical parameters were determined in weeks 1, 5
      and 11. In the 11th week, invasive haemodynamic parameters were measured, then
      the rabbits underwent autopsy, cardiac tissue was examined by light microscopy
      and scored semiquantitatively. The contents of calcium, potassium, magnesium,
      iron and selenium were measured in the left heart ventricle. DMPS administered
      alone was well tolerated and did not cause any major signs of toxicity. It
      decreased the cardiac content of calcium, but did not affect the iron
      concentration. In contrast to dexrazoxane, DMPS pre-treatment did not prevent the
      decline in body weight in weeks 8-11 caused by daunorubicin, actually worsened
      mortality (26.7% vs 40.0%), did not ameliorate daunorubicin-induced nephrotic
      syndrome, and did not prevent the occurrence of the severe myocardial lesions.
      Unlike dexrazoxane, a lack of protective effect of DMPS against chronic
      daunorubicin toxicity in rabbits was demonstrated. The underlying cause may
      consist in the fact that DMPS does not efficiently chelate tissue iron and thus
      may not prevent the formation of oxygen free radicals.

PMID- 12515047
TI  - Effect of atropine and the oxime HI-6 on low-level sarin-induced alteration of
      performance of rats in a T-maze.
AB  - 1. To study the influence of antidotes on low-level sarin-induced alteration of
      cognitive functions, male albino Wistar rats were exposed to three various low
      concentrations of sarin for 60 minutes in the inhalation chamber. One minute
      following sarin exposure, the rats were i.m. treated with the oxime HI-6 in
      combination with atropine. Control rats were treated with antidotes as
      experimental rats but exposed to the pure air instead of sarin. Cognitive
      functions of the rats were tested using a T-maze where spatial memory and spatial
      orientation were evaluated. The performance of sarin-exposed and treated rats in
      the T-maze was tested several times within six weeks (single exposure) or five
      weeks (repeated exposure) following inhalation exposure to evaluate cognitive
      impairments. 2. In the case of single exposure to sarin, no statistically
      significant differencies between the performances of the control and the
      experimental groups in the alteration of spatial memory and spatial orientation
      were observed. The repeated exposure of treated rats to clinically asymptomatic
      dose of sarin (LEVEL 2) did not change the effect of low-level sarin exposure on
      spatial memory of the experimental rats compared to the single exposure to the
      same dose of sarin. 3. The decrease in the T-maze performance of the control rats
      was caused by the impairments of rat's mobility due to the features of a solution
      of antidotes.

PMID- 12515048
TI  - Serum C-reactive protein and interleukin6 levels in neonatal sepsis.
AB  - In this article, we studied complete blood count, serum C-reactive protein (CRP)
      and interleukin (IL-6) levels in 30 newborn infants with sepsis at admission, in
      the 24th hour of admission and at the end of the treatment. Our purpose was to
      determine the relationship among these parameters in the early diagnosis of
      neonatal sepsis. In our study, there was not a significant difference in white
      blood cell (WBC) and thrombocyte count among the values of the first, 24th hour
      and end of therapy in the study group (P > 0.05). However, there was not a
      significant difference in B/N ratio among the values at admission, 24th hour and
      end of therapy in the study group (P > 0.05). Both serum CRP and IL-6 levels were
      found to be significantly higher than those of control subjects at the beginning
      (P < 0.05). Similarly, the values obtained on the 24th hour were also elevated.
      However, at the end of therapy both decreased to normal level (P < 0.05). Based
      on these data, we think that serum CRP levels only which is a simple method may
      be used in the diagnosis of neonatal sepsis. However, WBC and serum IL-6 levels
      may be useful to establish mortality, because there was a statistically
      significant difference for these parameters between the survivors and deaths (P <
      0.05).

PMID- 12515049
TI  - Maxillary sinus augmentation using deproteinized bovine bone (Bio-Oss) and
      Impladent Dental Implant System. Part I. Comparison between one-stage and two
      stage procedure.
AB  - This study was undertaken to compare implant survival after one- or two-stage
      sinus augmentation. Ninety-two maxillary sinuses in 77 patients were augmented
      with deproteinized bovine bone (Bio-Oss). These sinuses were sub-divided into two
      groups: Group 1 (n = 49) was operated on with a one-stage procedure, and Group 2
      (n = 43) with a two-stage operation. A hundred and eighty-five implants were
      inserted in these augmented sinuses. Clinical and radiographical evaluations were
      performed and recorded according to certain criteria. The follow-up period was
      ranging from 16 to 44 months. Out of the implants inserted using the one-stage
      procedure, all survived. Two implants failed in the two-stage procedure group
      (98.91% implant survival). This study showed that no statistically significance
      was observed between the two surgical techniques (P < 0.05). Therefore, the
      authors concluded the type of surgical procedure (one- or two-stage) has no
      effect on implant survival.

PMID- 12515050
TI  - Combined off-pump coronary revascularization and lung resection.
AB  - Concomittant severe coronary artery disease and lung malignancies occur rarely.
      Combined conventional coronary artery bypass grafting (CABG) with the use of
      cardiopulmonary bypass (CPB) with lung resection posses several perioperative and
      postoperative problems related to extracorporeal circulation and heparinization.
      The avoidance of CPB may be advantageous by decreasing blood loss, pulmonary
      complications and hospital stay. Further, exposure to the immunosuppressive and
      inflammatory effects of CPB may have deleterious impact on tumor growth and
      dissemination. Off-pump CABG makes the combined procedure safer as it abolishes
      the complications of CPB. We report two patients with the diagnosis of severe
      coronary artery disease and lung malignancies, underwent off-pump CABG and lung
      resections in the same surgical setting.

PMID- 12515051
TI  - You can get what you believe in.

PMID- 12515052
TI  - Clinical evaluation of visual, radiographic, and laser fluorescence methods for
      detection of occlusal caries.
AB  - The aim of this clinical study was to test cut-offs for occlusal caries detection
      by the laser fluorescence device DIAGNOdent (DD) in comparison to visual-ranked
      inspection (VI) and bitewing radiographs (BW) under condition of a general dental
      practice. 281 occlusal surfaces of permanent molars from 97 patients were
      examined with VI, DD and BW. Caries extent was verified by bioptical intervention
      (gold standard) of 248 molars. Upon biopsy no molar was assessed as caries free,
      24 teeth had caries confined to enamel and 224 teeth revealed dentine caries. For
      dentine caries detection DD achieved the highest values for sensitivity (0.93),
      specificity (0.63) and agreement (0.89) followed by BW with figures of 0.70, 0.96
      and 0.69, respectively. VI exhibited the lowest sensitivity (0.25) and agreement
      (0.25), but the highest specificity (1.00). It is advised to assess occlusal
      surfaces by a meticulous VI followed by the use of DD and/or BW as additional
      diagnostic tool of second choice. A DD value of > 20 could be confirmed as a
      sensitive cut-off for detection of occlusal dentine caries in first and second
      permanent molars. For the detection of early signs of enamel caries the DD seems
      to be less suitable.

PMID- 12515053
TI  - Periodontal diseases, caries, and microbial composition of the subgingival plaque
      in children: a longitudinal study.
AB  - The present study compares periodontal parameters, caries, and levels of colony
      forming units (CFU) of bacteria from subgingival plaque of permanent teeth, to
      those of primary teeth examined 4 years previously. Six children who had
      periodontitis and 5 who had no periodontitis in primary teeth (groups A and B
      respectively) were examined. The microbial examination included the number of CFU
      of the total anaerobic count, Actinobacillus actinomycetemcomitans, Streptococcus
      mutans and Porphyromonas gingivalis. The differences in CFU values for the
      permanent teeth between groups A and B were not significant. Group A had
      significantly higher gingival inflammation values in the permanent teeth than
      group B. Permanent teeth had significantly higher CFU values of P. gingivalis
      than the primary teeth. Based on the present limited sample, the number of CFU
      from bacteria of the subgingival plaque of primary teeth are not an adequate
      predictor of periodontal disease or caries in the permanent teeth.

PMID- 12515054
TI  - Atypical presentations of pediatric actinomycosis: report of a case.
AB  - It is well recognized that cervicofacial actinomycosis is rare in children,
      especially at maxilla. Actinomycosis involving the maxilla usually is seen as a
      localized intraoral infection in contrast to classical cervicofacial
      actinomycosis. In this article, we describe an 8-year-old patient who had
      actinomycosis involving the bone at the left maxillary lateral incisor region.
      The diagnosis was based on histologic report because of location and development
      of the lesion with unusual history. The treatment of choice was removal of the
      soft and hard tissues with concomitant prolonged penicillin administration. In
      cases of persistent oral infection the diagnosis of actinomycosis should be
      actively attempted through microbiologic and histologic examination.

PMID- 12515055
TI  - Clinical and microbiological changes in a child with rapid alveolar bone loss and
      refill.
AB  - A 10-year-old Japanese girl with severe tooth mobility in her lower permanent
      incisors was examined clinically, as well as radiographic and microbiological
      means. The incisors had severe alveolar bond loss and pocket depths exceeding 7
      mm at the first visit, however, 10 periodontal bacteria were not detected in
      subgingival plaque samples taken from the lower central incisors using a 16S rRNA
      based polymerase chain reaction method. Periodontal treatment consisting of
      mechanical debridement and antibiltic medication resulted in a significant
      improvement of the clinical parameters. Three months after the first examination,
      dental radiographs showed refilling of alveolar bone in the region. Further,
      microbiological examinations after remission detected only oral microflora
      commonly found in health children including A. actinomycetemcomitans. Based on
      the clinical, readiographic, and microbiological findings, the present case was
      diagnosed as acute periodontitis.

PMID- 12515056
TI  - Tooth eruption symptoms: a survey of parents and health professionals.
AB  - It is commonly believed that teething in infants can cause a variety of signs and
      symptoms. Previous studies have suggested an association between teething and
      fever, irritability, drooling, rashes, vomiting, diarrhea, night crying, and
      convulsions. PURPOSE: The objective of this study was to evaluate differences in
      the beliefs of pediatricians, pediatric dentists and parents regarding symptoms
      caused by teething in infants. METHODS: A survey consisting of demographic
      information and questions concerning commonly reported symptoms associated with
      teething was administered to 100 randomly selected Iowa pediatricians, all
      practicing pediatric dentists in Iowa (n = 33) and a convenience sample of 120
      parents from the greater Iowa City area. Responses were analyzed using the Chi
      square test. RESULTS: Response rates for each group were: pediatricians 45%;
      pediatric dentists 76%; and parents 50%. The majority of individuals in each
      group believed that teething in infants can cause swollen gums, drooling,
      irritability, inflamed gums, restlessness, sleeplessness, and fever. There were
      significant differences in the percent of agreement relating to drooling (p =
      0.001), inflamed gums (p = 0.001), and sleeplessness (p = 0.027). A greater
      percentage of pediatric dentists and parents agreed that these symptoms were
      caused by teething than did pediatricians. The largest difference between groups
      was related to the association between teething and diarrhea. The majority of
      parents (56.7%) and pediatric dentists (52.0%) believed that diarrhea is
      associated with teething compared to just 9.1% of pediatricians. CONCLUSIONS:
      These results support the hypothesis that differences regarding beliefs about
      teething symptoms exist between parents, pediatricians, and pediatric dentists.
      There is more agreement between parents and pediatric dentists than between
      either of these groups and pediatricians.

PMID- 12515057
TI  - Prevalence of developmental enamel defects in mentally retarded children.
AB  - Developmental defects of enamel (DDE) are commonly observed in children with
      neurological disorders. However, information related to these patients is very
      scarce. The purpose of this study was to determine the prevalence of DDE in
      mentally retarded children and to correlate it with specific perinatal factors
      and childhood diseases. A total of 170 retarded children between 4 and 17 years
      from a nonfluoridated area were examined. Teeth with defective enamel were seen
      in 37% of the patients. Permanent central incisors were the most affected teeth
      (68.38%). White/single opacities were present in 48.38% and white/diffuse patchy
      opacities in 28.38% of the patients. There was a significantly higher prevalence
      of DDE in patients with history of bacterial diseases. No statistically
      significant relation was found between presence of DDE and sex, nutritional
      status of the mother, use of alcohol and tobacco during pregnancy, presence of
      syndromes, neonatal disturbances and viral diseases.

PMID- 12515058
TI  - Clinical performance and survival of space maintainers: evaluation over a period
      of 5 years.
AB  - The study investigated the clinical performance of 387 space maintainers fitted
      in 358 patients aged from 3 to 9 years in the Department of Pediatric Dentistry
      at the Faculty of Dentistry-University of Jordan from 1996 to 2000. Failure
      occurred in 119 appliances (30.7%), of which 49.6% were due to solder breakage,
      32.8% from cement loss, 11% from soft tissue lesions, 4.2% from eruption
      interference, and 2.5% were completely lost. By using the Kaplan-Meier method,
      the estimated median survival time for space maintainers was 18 months. Lingual
      arches had the lowest median survival time of 14 months. Bands and loops, Nance
      appliances, and removable partial dentures had similar probability of survival.
      Fixed bilateral mandibular appliances recorded lower survival time than fixed
      bilateral maxillary appliances. Gender, age, type of dentition, fixed vs.
      removable, year of placement of the appliance and number of space maintainers
      fitted simultaneously in the same patient had no significant effect on survival
      of the appliances.

PMID- 12515059
TI  - Transitory pre-eruptive malposition of a maxillary canine: report of a case.
AB  - The ectopical eruption of the maxillary canine has been related to many causative
      factors. This paper shows a transient pre-eruptive abnormal position of a
      maxillary canine in a 9-year-old boy. The change from the normal position of the
      canine occurred coincidentally with the inflammation of the adjacent lateral
      incisor due to injury. The canine returned to a normal path after treatment and
      healing of the lateral incisor.

PMID- 12515060
TI  - Infraclusion of primary molars: a review and report of a case.
AB  - The term infraclusion is usually used to define mandibular primary teeth in
      posterior region that remain below the occlusion level. The degree of
      infraclusion depends on some factors like deviation below the occlusal plane, and
      infraclusion of tooth in the alveolar bone. Deficient eruptive force, disturbed
      metabolism of the periodontal ligament, trauma, local inflammation, deficient
      local vertical bone growth, disturbance in interaction between normal resorption
      and hard tissue repair, ankylosis and hereditary components have been given as
      etiological factors. Complications of infraclused primary molars are tipping of
      the neighboring teeth, space loss, supraeruption of the antagonists, and
      dislocations of permanent teeth lying under the primary tooth. In this case
      report, after reviewing the literature a patient with infraclused mandibular
      primary second molar has been examined to observe the complications of
      infraclusion. With an appropriate treatment approach, a proper condition was
      prepared for the eruption of permanent teeth.

PMID- 12515061
TI  - Larsen's syndrome with dental anomalies: report of a case.
AB  - Dental anomalies and mixed-type hearing loss are extremely rare symptoms of
      Larsen's syndrome that is characterized by multiple joint dislocation and flat
      face. A 15-year-old Turkish girl affected with Larsen's syndrome exhibiting many
      characteristic facial and skeletal features plus hitherto unreported oral and
      oral-facial anomalies including, maxillary prognathi, malocclusion, supernumerary
      teeth, macroglossia and microdontia is reported.

PMID- 12515062
TI  - Radiographic diagnosis of supernumerary teeth: report of six unusual cases.
AB  - The purpose of this report was to describe the radiographic findings of 6
      uncommon situations of supernumerary teeth in a Brazilian pediatric dentistry and
      orthodontic clinic. Six cases of supernumerary teeth were diagnosed in
      association with other dental anomalies such as number, position, and form. The
      supernumeraries were asymptomatic and were detected through routine radiographic
      examination. The importance of routine radiographic examination is emphasized for
      the correct diagnosis of supernumerary teeth, and avoidance of associated
      complications.

PMID- 12515063
TI  - Early diagnosis and treatment of supplemental mandibular tooth: report of a case.
AB  - This report describes a rare case of a supplemental tooth with a morphology
      similar to a lateral incisor, found in the canine region of the mandible of a 6
      year-old male. The purpose of this paper is to report the importance of early
      diagnosis and treatment during mixed dentition. The treatment was extraction of
      the primary mandibular left canine soon after the initial diagnosis of the
      condition to facilitate the spontaneous eruption of the supplemental tooth and
      his removal. Twenty-nine months after the removal of the supplemental tooth the
      mandibular left canine was fully erupted into normal position. No complication
      arose from the presence of this supernumerary and his early diagnosis has been
      very important for not disrupting the normal erupting or alignment of other
      teeth.

PMID- 12515064
TI  - Radiographic diagnosis of supernumerary premolars: case reviews.
AB  - The literature reported prevalence of supernumerary teeth within the mandible and
      maxilla varies from 0.2-0.9%. This study reviews the formation and diverse
      clinical appearances of supernumerary premolars. We present case reports where
      supernumerary teeth were recognized as incidental findings during routine
      radiographic examination in patients with an age range of five to thirty-nine
      years. Cases are presented to illustrate that the initiation and development of
      supernumerary premolars are often delayed by a magnitude of years. Periodic
      examination is recommended for occurrence and clinical behavior. In the presented
      cases, displacement and resorption of the adjacent teeth was not evidenced. None
      of the supernumerary teeth demonstrated cystic transformation. The importance of
      differential radiographic diagnosis is discussed.

PMID- 12515065
TI  - Congenital epulis: report of a case.
AB  - Congenital epulis of the new-born is a rare tumour, also known as Neumann's
      tumour described for the first time in 1871. Epulis usually present at birth and
      it has marked female preponderance of 10:1. Histiogenesis is uncertain,
      recommended treatment is excision. However as recurrence or damage to future
      dentition have not been reported, radical excision is not warranted. We reported
      a case of congenital epulis in a new-born female, with clinic investigations,
      surgical excision were not performed as it was not indicated for this case.

PMID- 12515066
TI  - An unusual mode of injury-implantation of a broken toothbrush medial to ramus:
      report of a case.
AB  - Impalement injury and implantation of a foreign body in the oral cavity is common
      in young children. Typically the child falls with the foreign body in the mouth
      resulting in implantation of the object at various sites in the oral cavity. It
      is quite unusual to have the head of a toothbrush with bristles implanted fully
      in the soft tissue medial to the ramus, in the region of pterygomandibular space,
      following an injury with a cricket ball without a history of fall. A case of an
      unusual foreign body implanted at an unusual site by an unusual injury is being
      presented.

PMID- 12515067
TI  - Fluoride content of infant foods in Brazil and risk of dental fluorosis.
AB  - The aim of this work was to analyze total F (TF) and HCl 0.01 M ("gastric juice")
      soluble F (SF) of infant foods and beverages. Samples were divided into 3 groups:
      children cereals (A), chocolate milk (B) and soy beverages (C). Mean TF
      concentrations +/- SD (amplitude, unit mg F/mL or mg F/g) were: A) 4.255 +/-
      3.038 (0.200-7.840, n = 6); B) 0.345 +/- 0.469 (0.047-1.272, n = 6); and C) 0.153
      +/- 0.070 (0.092-0.295, n = 8). Five samples of cereals and one sample of
      chocolate milk were analyzed for SF. In cereals analyzed for SF, all F was
      soluble, while for the chocolate milk, approximately 50% of TF was soluble. It
      was observed that some of the cereals and beverages analyzed may be important
      contributors for total daily fluoride intake. When consumed just once per day,
      they may supply up to 25% of the maximum recommended daily F intake (0.07 mg F/Kg
      body weight) for a 2-year-old child (12 Kg).

PMID- 12515068
TI  - Abnormal pulp calcification in primary molars after fluoride supplementation.
AB  - Forty-five caries-free primary molars from children with continuous fluoride
      supplementation (n = 28) after birth and from children without fluoride
      prophylaxis (n = 17) were investigated by light microscopy. The following results
      were obtained: The prophylaxis group evidenced a special form of calcification
      consisting of fibrodentin-like hard tissue developing intramurally in the dentin
      wall especially at the pulp floor and spreading irregularily into the pulp cavity
      by displacing the degenerating pulp tissue (n = 24). These teeth were ankylosed
      in the bi- and trifurcation area as well as inside the roots. This kind of hard
      tissue was not observed in the teeth from untreated children. Only 5 children had
      greater calcifications attached at the pulp wall. Nevertheless, this difference
      was statistically significant (p = 0.001) and indicates a relationship between
      fluoride prophylaxis, the special form of pulp calcification and tooth ankylosis.

PMID- 12515069
TI  - Attitudes concerning mouthguard use in 7- to 8-year-old children.
AB  - The purpose of this study was to determine the acceptance of 3 types of
      mouthguards 1) stock, 2) boil and bite, and 3) custom-made by 7-8 year old
      children playing organized soccer. Three teams volunteered to participate and the
      type of mouthguard was randomly selected for each team. The children were fitted
      for the mouthguards and after wearing them, a questionnaire was returned to the
      investigator. Eighty two percent of the children wearing custom made mouthguards
      and 87% of the boil and bite ranged from happy to enthusiastic about its use.
      None of the children provided stock mouthguards reported liking their use. Only 1
      child in the custom group failed to wear the appliance during practice and games
      while the children in the stock group ranged from 20% to all of the time. Ninety
      five percent of the parents believe that children should wear mouthguards when
      injuries may occur. However, only 24% of the parents would be willing to pay
      $25.00 for this protection. It is concluded that mouthguards will be used by
      children during organized sports activities if they fit.

PMID- 12515070
TI  - Dental care for special needs patients: a survey of Texas pediatric dentists.
AB  - The purpose of this study was to determine the amount of time Texas pediatric
      dentists spent, as both residents and in their professional position, in the
      treatment of special needs patients. In addition, an attempt was made to
      determine the dental services offered to these patients along with the barriers
      to obtaining care. A survey was mailed to the 334 members of the Texas Academy of
      Pediatric Dentistry. From the returned surveys (61.9% or 207/334) the following
      conclusions were drawn: 1) Most respondents had a significant portion of their
      training program devoted to special patient care, 2) Virtually all reported
      treating some special needs patients in their professional position, 3) Most
      provided conscious sedation and general anesthesia and adjuncts to behavior
      management for these patients, 4) Insufficient financial reimbursement was a
      major reason cited for not providing dental services to more of these patients.

PMID- 12515071
TI  - An overview of the 72.3 million children reported in the 2000 census.
AB  - A review of the 2000 census provides a general appreciation of the evolving
      demographic characteristics of the greatest number of youngsters in our nation's
      history.

PMID- 12515072
TI  - Macular disease. Introduction.

PMID- 12515073
TI  - Arteriovenous sheathotomy for branch retinal vein occlusion.
AB  - Branch vein occlusion is a significant cause of visual loss attributed to retinal
      vascular disease and is second only to diabetic retinopathy. BVO nearly always
      occurs at an AV crossing because of compression of the vein by the artery,
      resulting in hemodynamic abnormalities in the vein, including thrombus formation,
      reversal of flow toward the artery, and AV collateral formation. Relatively
      little information is available on the natural history of BVO; most of what
      exists is derived from clinical trials, including the BVOS. Current treatment
      options focus on treating sequelae of the occluded venous branch, such as macular
      edema, retinal neovascularization, vitreous hemorrhage, and traction retinal
      detachment. A novel therapeutic approach is decompression of the AV crossing,
      which has had promising initial results including restoration of vision and
      reversal of hemodynamic abnormalities. A prospective, controlled, clinical trial
      is being organized to determine the role of AV sheathotomy in the treatment of
      BVO.

PMID- 12515074
TI  - Limited macular translocation: current concepts.
AB  - Macular translocation is a promising treatment modality that offers patients a
      chance to improve their vision, potentially to a level that may allow reading and
      driving. Proper patient selection avoids surgery in eyes with permanently damaged
      central retina and identifies eyes with the greatest potential for good visual
      outcomes. Functionally, those patients with recent-onset subfoveal CNV without
      permanent foveal neurosensory retina damage have the greatest likelihood of good
      visual outcome. Use of fixation evaluation by means of the SLO appears to greatly
      optimize patient selection. Anatomically, the best candidates have small minimum
      desired translocations and healthy RPE-Bruch membrane-choriocapillaris complex
      beyond the borders of the lesion. The exact role of limited macular translocation
      for the management of subfoveal CNV in this era of photodynamic therapy remains
      to be evaluated, and a pilot multicenter, randomized, clinical trial is under way
      to compare the efficacy of limited macular translocation with photodynamic
      therapy in eyes with subfoveal CNV secondary to AMD.

PMID- 12515075
TI  - Use of radiation in the treatment of age-related macular degeneration.
AB  - In this century, macular degeneration is likely to reach epidemic proportions.
      New treatment modalities are being evaluated for wet or neovascular age-related
      macular degeneration (AMD) and include radiation treatment. Radiation is known to
      potentially destroy vascular tissue, and low-dose radiation has been shown to
      inhibit new blood vessel growth. Potential advantages to radiation therapy in
      treating AMD include the absence of iatrogenic mechanical or laser damage, the
      absence of systemic side effects, and the absence of local side effects caused by
      periocular and intraocular injection. An additional advantage is that eyes with
      primarily large, occult choroidal neovascularization are potentially eligible for
      treatment, and only one treatment would be necessary. The major potential side
      effect is radiation retinopathy, which is dose dependent.

PMID- 12515076
TI  - Management of submacular hemorrhage.
AB  - Submacular hemorrhage is a vision-threatening complication of choroidal and
      retinal disease. Visual outcome after submacular hemorrhage is dependent on the
      underlying disease process, amount of subretinal hemorrhage, and duration before
      treatment. Treatment options include observation, surgical evacuation with or
      without tissue plasminogen activator (tPA), or pneumatic displacement with or
      without tPA. The preoperative amount of subretinal hemorrhage may help dictate
      what treatment modality is chosen.

PMID- 12515077
TI  - Antiangiogenesis agents.
AB  - Although these preliminary results on the use of antiangiogenesis drugs for the
      treatment of neovascular AMD appear promising, double-masked, placebo-controlled,
      multicenter clinical trials are needed to demonstrate the therapeutic efficacy of
      such treatments. For example, the first antiangiogenesis drug tested in AMD,
      interferon alpha-2a, raised great enthusiasm. Indeed, interferon alpha-2a had
      been shown to be antiangiogenic in animal and in vitro models. It proved to be
      ineffective, however, in halting the progression of neovascular AMD in a double
      masked, placebo-controlled clinical trial [28]. Another antivasogenesis drug
      tested in a phase 3 clinical trial is thalidomide [67]. Although the enrollment
      of patients is finished, the results are not yet known.

PMID- 12515078
TI  - Genetics update of macular diseases.
AB  - Significant progress has been made in recent years in the discovery of genes
      causing early-onset inherited macular diseases [54]. The identification of these
      genes and their disease-causing mutations can aid in the diagnosis of patients
      who are genetically affected but have not yet developed the clinical phenotype.
      By understanding the primary defect in the pathophysiology of these diseases,
      treatment can be directed to the earlier stages in disease pathways, perhaps
      delaying or preventing the onset of vision loss. Furthermore, the disease gene
      could be replaced with a normal copy, allowing expression of the normal protein
      and potentially avoiding the disease phenotype altogether. Much work remains to
      elucidate the biologic mechanisms by which these genetic mutations result in
      disease phenotypes. Understanding the interaction of the disease genes with
      genetic background resulting in a normal phenotype, as in Best disease, or a
      completely different clinical entity, as in RDS-associated pattern dystrophy,
      could lead to useful therapies for these and other macular diseases. Animal
      models created by removing the normal genes, similar to what was performed with
      ABCA4, can assist in the development of therapeutic interventions. Further
      insight into the biochemical processes that cause macular dystrophies, including
      AMD, will contribute to our ability to develop treatments that will become
      increasingly vital in the years to come.

PMID- 12515079
TI  - Update on pseudophakic cystoid macular edema treatment options.
AB  - As far as the treatment of chronic pseudophakic CME is concerned, it is important
      to understand that postoperative CME usually resolves with time. One must gauge
      the various treatment modalities outlined above with improvements in visual
      acuity and decreasing clinical macular thickening. Mild cases usually require no
      treatment, whereas those that entail clinically significant reductions in vision
      or macular thickening do require appropriate intervention.

PMID- 12515080
TI  - Photodynamic therapy for choroidal neovascular disease: photosensitizers and
      clinical trials.
AB  - Photodynamic therapy with visudyne for choroidal neovascular disease (CNV) has
      proved effective at preventing moderate to severe visual loss in eyes with
      subfoveal predominantly classic CNV or occult-only CNV caused by age-related
      macular degeneration (AMD) and in eyes with subfoveal CNV caused by pathologic
      myopia. PDT is not meant to improve visual acuity. It should, therefore, be used
      in eyes with potentially useful macular vision. Clinical trials are under way to
      evaluate the usefulness of early retreatment with PDT and visudyne at 6 weeks for
      reducing the risk for moderate visual loss in eyes with predominantly classic
      CNV, the efficacy of PDT with visudyne for the treatment of AMD in eyes with
      minimally classic CNV, and the efficacy of PDT for use with SnET2, lutetium
      texaphyrin, and Npe6.

PMID- 12515081
TI  - Submacular surgery trials update.
AB  - Submacular surgery is a method of therapy for subfoveal CNV from multiple causes.
      It was first reported in the late 1980s. Since then, refinements in patient
      selection and surgical technique have reduced complications and made it a viable
      alternative to existing treatments and natural history for this condition. The
      Submacular Surgery Trials (SST) is a series of prospective, randomized,
      multicenter clinical trials designed to evaluate submacular surgery for exudative
      and hemorrhagic subfoveal CNV from AMD and for exudative subfoveal CNV from OHS
      and idiopathic causes. Recruitment has been completed for these trials, and the
      DSMC is continuously monitoring safety and efficacy and evaluating any
      modifications of study design to accommodate new therapies for subfoveal CNV.

PMID- 12515082
TI  - Posterior pole tumor update.
AB  - This chapter focuses on the diagnosis and management of choroidal melanoma in
      light of recent findings from the COMS. Retinoblastoma is emphasized to describe
      recent trends in primary treatment away from EBRT and toward chemoreduction with
      local therapy. In addition, vascular and glial tumors of the retina and tumors of
      the retinal pigment epithelium are described because of the association between
      these lesions and systemic disease. Recent advances in treatment and genetic
      testing for these diseases are discussed. Finally, ocular metastasis, intraocular
      lymphoid tumors, and intraocular leukemia are included because of their
      importance in determining systemic treatment and prognosis. The chapter gives an
      overview of important posterior pole tumors and highlights recent developments in
      the management of each intraocular disease process.

PMID- 12515083
TI  - Macular features of pediatric surgical vitreoretinal diseases.
AB  - We discuss herein several pediatric vitreoretinal diseases that have
      characteristic macular features. Although some of these changes are subtle, they
      offer important diagnostic and prognostic information. Most of these conditions
      require close follow-up and timely surgical intervention. Several important
      surgical considerations are mentioned.

PMID- 12515084
TI  - Medications and retinal toxicity.
AB  - Approximately three dozen medications have been associated with retinal toxicity,
      and it is important to be aware of such associations. Several medications, such
      as acetazolamide and latanoprost, are commonly prescribed by the ophthalmologist.
      Most of the other medications are commonly administered by the patient's primary
      physician. When assessing any patient for a retinal disturbance, it is imperative
      to question the patient regarding the use of systemic medications. This is
      especially important as more and more medications are brought to the market each
      year.

PMID- 12515085
TI  - Cytomegalovirus retinitis in the era of combined highly active antiretroviral
      therapy.
AB  - Advancements in antiretroviral therapy have changed the way we view and treat
      cytomegalovirus retinitis (CMVR). At one time the diagnosis of CMVR necessitated
      that most patients undergo daily intravenous infusions of anti-CMV agents. Today,
      after the restoration of their immune systems, they are able to stop maintenance
      anti-CMV therapy. HAART failure, resistant strains of CMV, and immune recovery
      uveitis are growing challenges.

PMID- 12515086
TI  - Polypoidal choroidal vasculopathy.
AB  - Polypoidal choroidal vasculopathy seems to be a distinct clinical entity that
      should be differentiated from other types of CNV associated with AMD and other
      known choroidal degenerative, inflammatory, and ischemic disorders. The principle
      abnormality seen in PCV, notably the branching vascular network and polypoidal
      structures at the borders of the lesion, seem to be unique to the disorder. In
      patients with serosanguineous detachment of the pigment epithelium, particularly
      in those with increased risk factors such as African American or Asian race, ICG
      should be performed to evaluate the choroidal vascular abnormality to establish a
      more definitive diagnosis. If the characteristic vascular lesion of PCV is seen,
      a conservative approach to management should be taken unless there is a
      persistent or progressive exudative change that threatens the central macula. In
      that event, there may be a rationale for photo-coagulation treatment of leaking
      aneurysmal or polypoidal components within the vascular lesion, but not the
      entire vascular complex. Photodynamic therapy seems to be a promising therapeutic
      modality, but randomized clinical trials are needed to establish the efficacy and
      safety of the PDT treatment in the management of these patients.

PMID- 12515087
TI  - Diabetic macular edema: review and update.
AB  - Impairment in the visual acuity and quality of life of diabetic patients with
      macular edema can undeniably be decreased with systemic and ocular therapeutic
      intervention, as shown by numerous controlled studies. Such interventions, with
      early screening and periodic examination, are even more crucial given the
      increasing survival of patients with diabetic retinopathy. In the 1950s, adjusted
      5-year survival rates for patients with PDR were less than 30%, whereas by the
      end of the century age- and sex-adjusted 5-year survival rates approached 90% for
      patients with early-onset diabetes and 60% for patients with late-onset diabetes
      [83]. Furthermore, advances in our understanding of diabetic retinopathy have led
      to biochemical adjuncts that offer the potential for further reduction of visual
      loss caused by diabetic macular edema. Despite such advances, the implementation
      of effective treatments has been hampered by concerns over hypoglycemia after
      intensive insulin regimens, poor physician compliance regarding guidelines for
      dilated ophthalmic examinations, and economic barriers to access [84]. Therefore,
      it is imperative for the ophthalmologist not only to discuss the progression and
      treatment of diabetic macular edema and the importance of routine examination
      with patients but also to work with other health care professionals to ensure the
      evaluation and treatment of associated cardiovascular and neurologic disease.
      Educational programs, such as those created by the National Eye Health and
      Education Program [85], may also assist the ophthalmologist in providing patients
      with the optimal care available in the 21st century.

PMID- 12515088
TI  - Macular holes.
AB  - Spontaneous closure of macular holes occurs in 3% to 9% of patients over 6 years
      [3,58]. Visual acuity can recover dramatically once the hole closes. The risk for
      hole development in the fellow eye in the absence of PVD is approximately 29%.
      The presence of vitreomacular separation reduces the risk to less than 5%. Most
      of the fellow eyes that develop macular holes do so within 2 years [59]. Macular
      hole surgery has been evolving. ILM peeling is a recent, widely accepted
      innovation. Meta-analysis of 12 published case series indicates anatomic success
      in 77% and functional success in 55% of patients with the traditional technique
      of epiretinal peeling and no adjuvant use. Meta-analysis of 22 series with
      techniques using adjuvants indicates an anatomic success rate of 81% and a
      functional success rate of 60%. Meta-analysis of 4 studies involving 221 cases
      indicates an anatomic success rate of 96% and a functional success rate of 81%
      [5]. True superiority of one approach versus another cannot be determined without
      a randomized, prospective clinical trial, which is unlikely to be conducted. In
      the meantime, surgeons must choose an approach based on individual features of a
      given patient and their own surgical experience.

PMID- 12515089
TI  - [Functional activity of ABC transporters (markers of multidrug resistance) in
      human colon adenocarcinoma and normal colonic mucosa].
AB  - Functional activity of multidrug resistance (MDR) markers (total activity of ABC
      transporters, P-glycoprotein (Pgp) and multidrug resistance-associated protein
      (MRP) activities) in human colon adenocarcinoma and normal mucosa was examined.
      Functional activity of ABC-transporters was revealed in all colon tumors and in
      70% of normal mucosa samples investigated. Expression of Pgp and MRP functional
      activity was determined in about 50% and 70% of colon tumors respectively.
      Pgp+MRP+ phenotype was determined in 36% of normal mucosa and adenocarcinoma
      samples. Expression of Pgp+MRP- phenotype was practically the same in normal
      mucosa and tumors (in 10 and 18% of samples respectively). Pgp-MRP+ phenotype was
      revealed two times more often in tumors than in mucosa--in 36 and 18%
      respectively. On the contrary, Pgp-MRP- phenotype was detected more rarely in
      tumors than in mucosa (in 10 and 36% of samples respectively). Transporters
      different from Pgp and MRP were also determined in some tumors and normal mucosa.
      At the patients with expression of Pgp function in normal mucosa the activity of
      the transporter was revealed in 25% of tumor samples only. On the contrary, at
      the patients with expression of MRP function in normal mucosa the activity of the
      transporter was revealed in 70% of tumor samples. At the patients with no
      expression of Pgp or MRP activity in normal mucosa the function of the
      transporters in tumors was determined in 60% and 70% of samples respectively. It
      is concluded that functional activity of various ABC-transporters (Pgp, MRP and
      other different from Pgp and MRP) is expressed in human colon adenocarcinoma;
      expression of ABC-transporters functional activity in normal mucosa does not
      predict MDR phenotype of the tumor.

PMID- 12515090
TI  - [Ani immunomodulator Hepon inhibits hepatitis C virus replication in human cell
      cultures in vitro].
AB  - Antiviral activity of immunomodulator "Hepon" was evaluated in human cells
      culture infected with hepatitis C virus. "Hepon" presence protected human cells
      SW-13 from cytopathogenic effect of hepatitis C virus. Maximum antiviral effect
      was demonstrated by "Hepon" at concentration 1 mcg/mL. Control antiviral agent
      reaferon (interferon alfa-2a) was more potent as vitality protecting agent in the
      case of SW-13 human cells culture. "Hepon" activity is based on changes of
      cytokins and interferons spectrum so this immunomodulator is expected to be
      effective against different viruses including herpes virus and encephalocarditis
      virus.

PMID- 12515091
TI  - [Dynamics of antibiotic resistance of purulent septic pathogens at an emergency
      facility].
AB  - The predominant pathogens at the emergency medicine hospital were analysed and
      its resistance to antibiotics was investigated in dynamics. The susceptibility of
      the pathogens was analysed by the method of dynamic equalibration. Statistically
      significant reduction of resistant bacteria isolation was demonstrated for 2
      species of 7--that is S. aureus and E. faecalis regarding 4 antibiotics. The
      ratio of staphylococci resistant to cefazolin, ceftazidime, doxycyclin reduced,
      the ratio of enterococci resistant to chloramphenicol and doxycyclin also
      diminished. No correlation was demonstrated between the pathogen isolation
      frequency and ratio of resistant strains.

PMID- 12515092
TI  - [Current possibilities and perspectives of the combined treatment of patients
      with severe bronchopulmonary diseases].
AB  - Complex treatment with ceftriaxone (or ceftazidime) and intravenous
      immunoglobulin G (Biaven V. I.) was performed at 21 patients with severe
      pneumonia and tracheobronchitis complicated by immunedeficient status
      (myasthenia, diabetes mellitus etc). The results of the treatment proves strong
      tendency to normalization of the immune system (ceruloplasmin level, CIC,
      catalase, immunoglobulins) along with clinical signs regression.

PMID- 12515093
TI  - [Discussion on bacteremia and sepsis].

PMID- 12515094
TI  - [A novel anti-HIV agent--agenerase].

PMID- 12515095
TI  - [Levofloxacin in the treatment of respiratory infections].

PMID- 12515096
TI  - [Azithromycin in the treatment of acute otitis media].

PMID- 12515097
TI  - [The Cardiology college of general hospitals].

PMID- 12515098
TI  - [Will the demographic evolution endanger the survival of the departments of
      cardiology in French General Hospitals within 15 years?].

PMID- 12515099
TI  - [Validation of a diagnostic algorithm in non severe pulmonary embolism at the
      Annecy general hospital. D-dimers, venous lower limb ultra-sound and spiral CT
      scan].
AB  - OBJECTIVE AND METHOD: We have evaluated the sensitivity of a diagnostic algorithm
      for all patients suspected of pulmonary embolism using: D-Dimer, lower limb
      venous ultrasonography and helical computed tomography. To validate this
      approach, a lung scan is systematically carried out if the pulmonary embolism
      diagnosis is not withheld as a result of the algorithm. Clinical tests are
      organised between the 3rd and 6th month. RESULTS: Two hundred patients were
      involved between January 1998 and October 1999. One hundred and six pulmonary
      embolisms were diagnosed. Out of the 200 ultrasonography tests carried out we
      found: 71 proximal deep-vein thrombosis (popliteal or supra-popliteal), 33 distal
      thrombosis (infra-popliteal). Ninety-two cases were negative (4 tests non
      conclusive). We have deduced that a deep-vein thrombosis permits the diagnosis of
      thrombo-embolic illness without any further diagnostic approach (no computed
      tomography). Out of the 129 computed tomographies carried out we found: 35
      pulmonary embolisms and 23 other diagnoses. Seventy-one lung scans were therefore
      carried out. We recorded 7 discordances (scans showed high and very high
      probability for pulmonary embolism whilst computed tomographies did not):
      pulmonary angiography was negative 4 times and diagnosed pulmonary embolism once
      and two patients refused to take the test (Table 2). There are two recurrences in
      the follow-up: proximal thrombosis and a pulmonary embolism. This involved two
      patients who had refused to undergo pulmonary angiography. CONCLUSION: This
      diagnostic approach therefore seems satisfactory but would require further
      investigation on a wider scale.

PMID- 12515100
TI  - [Heart failure clinics. Concept, organization, results].
AB  - Chronic heart failure is linked to high rate of death and hospitalization. Some
      studies have highlighted the beneficial effect of heart failure clinics on
      morbidity and mortality. We have developed this type of structure at CHR Dubos
      since 3 years and we have recently created an heart failure clinic (10 beds).
      It's based on a concept including an experienced medical and nurse team,
      patient's and patient's family education and evaluation of the structure.

PMID- 12515101
TI  - [Coverage of pointed acute coronary syndromes in the general hospital centers].
AB  - This study presents data on the management of acute coronary syndromes collected
      in a national registry organized by the french College national des cardiologues
      des hopitaux generaux in September 2000. In all 86 institutions participated and
      data from 607 patients (mean age: 67 years; 413 men) were analysed. The final
      diagnosis was unstable angina in 38%, non-Q wave myocardial infarction in 21% and
      Q-wave myocardial infarction in 40.5%. Median time to admission was 4 h. At
      symptom onset, patients called their general practitioners in 46% of cases,
      emergency ambulatory units in 31% of cases and arrived to the hospital on their
      own in 23% of cases. Observance of the European Society of Cardiology guidelines
      was good for patients without ST segment elevation. In patients with ST segment
      elevation, 9% had pre-hospital thrombolysis, 28% hospital thrombolysis, and 27%
      had angioplasty within 48 h of admission, including 9% with rescue angioplasty.
      Overall, 57% of patients with ST segment elevation received reperfusion therapy.
      In hospital mortality was 6% for the whole cohort, and 11% for patients with
      acute myocardial infarctions. By multivariate analysis, predictors of in-hospital
      mortality were age, type of acute coronary syndrome, absence of beta-blocker
      therapy, and absence of coronary angiography.

PMID- 12515102
TI  - [Off-pump beating heart coronary artery bypass. Technical points of view and
      surgical results].
AB  - A consecutive series of 746 patients undergoing heart beating myocardial
      revascularization was reviewed. An average of 2.30 grafts/patients was performed.
      The rate of mortality in the first 30 postoperative days was 0.28%. Two cases had
      to be terminated on-pump. We used the inotropic drugs in 0.6% of cases. The
      postoperative events were: atrial fibrillation (12.6%), myocardial infarction
      (0.3%). The rate of transfusion was 7.4%. The extubation was performed in the
      first 24 h postoperatively in 94.7% of cases. The majority of patients (91.3%)
      left the hospital in the first 8 d postoperatively. Off pump coronary artery
      bypass grafting gives good result for the most of the patients even for those
      with multiple vessel disease and high operating risk.

PMID- 12515103
TI  - [Coronary artery disease observed in general hospitals: ETTIC study. Comparison
      between trimetazidine and mononitrate isosorbide for patients receiving
      betablockers].
AB  - The extended use of interventional surgery of revascularisation has modified the
      prognosis and the evolution of ischaemic heart diseases. However, both coronary
      artery bypass graft and percutaneous transluminal coronary angioplasty failed to
      make the symptomatic or subclinical ischaemic manifestations of chronic coronary
      insufficiency disappear. The interest of using betablockers as a first-line
      therapy was widely demonstrated. However, their combination with another
      efficient molecule is often necessary. The aim of this trial has been to
      appreciate the efficiency of the association of a betablocker with either
      trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients
      retaining a positive effort test despite 100 mg of atenolol, received in
      addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide
      mononitrate (92 cases) for a two-month period and are then re-evaluated at the
      end of this period. The ischaemic threshold is delayed in a significant way in
      both groups (p < 0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%).
      Twenty-three percent of the exercise tests under trimetzidine and 19% under
      isosorbide mononitrate become negative after two months of the therapeutic
      combination. The clinical improvement is even clearer with the disappearance of
      the angina crisis during the week before the second exercise test in 63% of the
      cases under trimetazidine and 54% of the cases under isosorbide mononitrate,
      among the patients who had kept it under atenolol at the inclusion. In
      conclusion, the combination of a second efficient molecule, trimetazidine or
      isosorbide mononitrate, brings a functional and objective improvement to patients
      with insufficient chronic coronary disease not totally controlled using a
      betablocker, even with high dosage. One should notice two important advantages in
      favour of the trimetazidine: one is practical due to a better tolerance (lack of
      cephalalgia), the other is conceptual (use of the complementary metabolic
      approach of cellular oxygenation rather than the haemodynamic approach of nitrate
      compounds which are already in concurrency with all other anti-ischaemic
      molecules).

PMID- 12515104
TI  - [Aortic stenosis with left ventricular dysfunction: evaluation and management].
AB  - Aortic stenosis is the most frequent valvulopathy in France today. Valve
      replacement has transformed the prognosis, when indications are present before
      the appearance of irreversible left ventricular dysfunction. However, some
      patients are still not seen before this time or their surgery was deferred. Thus,
      the postoperative prognosis depends on the reversibility of this dysfunction
      which can occur even when the stenosis is severe and essentially reflects the
      elevated afterload. The prognosis is less favorable once myocardial fibrosis has
      developed in response to left ventricular hypertrophy or when ischemic
      cardiopathy contributes to this dysfunction. The diagnosis and prognosis are
      based on the confirmation of the presence of a severe stenosis and that the
      removal of this obstacle will lead to regression of the dysfunction. For this,
      Doppler echocardiography is determinant, as combined with a dobutamine test, it
      is able to evaluate the tightness of the stenosis, the severity of the left
      ventricular dysfunction and its reversibility. When the stenosis is severe with
      contractile reserve, indicating a better postoperative prognosis, dobutamine does
      not induce an appreciable change of the aortic area, but the mean pressure
      gradient, often low prior to dobutamine administration, rises. Although the
      surgical risk remains higher in the presence of left ventricular dysfunction, the
      ultimate prognosis is more favorable when the test suggests regression is
      possible.

PMID- 12515105
TI  - [Usefulness of Doppler echocardiography in the diagnosis of acute diastolic heart
      failure in the elderly].
AB  - PURPOSE: To evaluate the clinical usefulness of the determination of Doppler
      mitral inflow pattern and new combined indices using colour M mode velocity flow
      propagation (Vp) in the diagnosis of acute diastolic heart failure in the
      elderly. METHODS: Total serum protein concentration (P, g/l) and E/A, E/Vp and
      1000/(2 x IRT + Vp) Doppler indices (E and A: mitral inflow peak velocities; IRT:
      isovolumic relaxation time) were measured at the time of therapy initiation in 94
      patients with left ventricular ejection fraction > 50% (78 +/- 13 years), 56 with
      pulmonary edema and 38 patients with acute respiratory disease. RESULTS: The
      feasibility was 73, 90 and 89% for E/A, E/Vp and 1000/(2 x IRT + Vp)
      respectively. The sensitivity, specificity and accuracy were 94-56-72%, 84-86-85%
      and 92-86-89% for E/A > or = 1, E/Vp > or = 2 and 1000/(2 x IRT + Vp) > or = 6
      respectively in the diagnosis of pulmonary edema in patients with normal serum
      colloid osmotic pressure defined by P > or = 60 g/l, and 41-50-43%, 37-86-50% and
      22-100-42% in patients with low colloid osmotic pressure (P < 60 g/l).
      CONCLUSIONS: The mitral inflow measurement is limited in most of cases of acute
      diastolic heart failure in the elderly by confounding factors such as atrial
      fibrillation and normalised pattern. New combined Doppler indices are useful in
      these patients, however, their value must be interpreted according to the serum
      colloid osmotic status estimated by total serum protein concentration.

PMID- 12515106
TI  - [Resynchronization of the failing heart by pacing].
AB  - Cardiac pacing has been proposed for patients with advanced heart failure
      refractory to optimal drug treatment and having conduction disorders to
      resynchronize mechanical activity of the heart. Activation asynchronism as caused
      by bundle branch block results in alteration of systolic function and
      arrhythmias. A too short or too long atrio-ventricular delay can also affect
      diastolic ventricular filling. Early clinical studies showed a benefit of very
      long atrioventricular delays shortening, not confirmed by further studies. Direct
      stimulation of the left ventricle was beneficial in acute hemodynamic studies.
      Three controlled clinical studies now completed, PATH-CHF, MYSTIC and MIRACLE
      have showed a functional benefit. Other studies (COMPANION, CARE-HF) are
      currently in process to evaluate the effect on survival and the interest to
      associate an automatic defibrillator. Technical aspects are also under
      investigation: optimal lead placement in the coronary venous system, types of
      leads, special pacing devices. This paper reports the experience of the first 50
      patients treated with multisite pacing in Aix-en-Provence general hospital, 33
      men and 17 women, 71 years of mean age, on NYHA class III or IV, and showing QRS
      width above 120 ms. During the follow-up (mean duration 16 months) 15 deaths
      (30%) happened. The benefit on NYHA class was 1.34; rehospitalization rate was
      low. Coronary sinus access was successful in 100% of cases. Sixteen per cent had
      a reintervention for lead displacement or threshold elevation. Left
      atrioventricular crosstalk, observed in six patients, supports the use of devices
      with three independent channels. Echocardiography is of interest for responders
      identification, optimal device programming and follow-up.

PMID- 12515107
TI  - [What is the place of aspirin in venous thrombosis prophylaxis?].
AB  - Since Virchow triade, it is well established that venous thrombosis is a
      multifactorial process involving various cellular and plasmatic protagonists.
      Aspirin antihrombotic efficacy seems not only due to its antiplatelet effects and
      thromboxane A2 synthesis inhibition. Anti-Platelet Trialists Collaboration
      metaanalysis stressed in 1994 the interest of aspirin treatment leading to 40%
      reduction of thrombosis relative risk. Regarding studies heterogeneity and
      outcomes criteria variety, its use in such context remains a matter of debate. Is
      the recent publication of PEP trial showing a significant decrease of pulmonary
      embolism mortality (0.6 versus 0.3%, p = 0.03) able to reinforce aspirin use in
      venous thrombosis prophylaxis? Were numerous and consecutive criticisms
      justified? Is there still a potential indication for aspirin in this setting? The
      experts of the last ACCP consensus conference recommended not to recommend
      aspirin in venous thrombosis prophylaxis with the highest level of evidence
      (grade A).

PMID- 12515108
TI  - ED managers react to threat against hospitals: here are security strategies.
AB  - A recent terrorist threat against hospitals has put emergency departments on
      heightened alert. Lockdown procedures are being practiced. Identification badges
      are worn by staff and visitors. Tabletop exercises using bomb threat scenarios
      are being held.

PMID- 12515109
TI  - Do you know who will be vaccinated at your ED?
AB  - The administration of the smallpox vaccine is imminent, so emergency department
      managers are making difficult decisions about which individuals should be
      vaccinated. If all attending physicians are vaccinated, these individuals can
      care for patients with suspected smallpox. Consider offering vaccine first to
      staff who have been immunized previously. Survey staff to find out which
      individuals have contraindications for the vaccine.

PMID- 12515110
TI  - Critical-care transport team improves care.
AB  - A critical-care transport team can prevent adverse outcomes, improve patient
      flow, and reduce delays. The team carries equipment and medications that can save
      a patient's life. Emergency department (ED) nurses can remain in the department,
      instead of having to transport patients for diagnostic tests. Transport nurses
      assist with resuscitations of trauma patients in the ED.

PMID- 12515111
TI  - Could your ED meet a 15-minute service pledge?
AB  - Patients dissatisfied with long waits is one of the most pressing problems that
      emergency department (ED) managers must address, and there is a trend of EDs
      offering service guarantees to patients to obtain higher satisfaction scores. At
      participating EDs, patients are offered letters of apology, movie passes, or a
      free visit if the guarantee isn't met. Census increased dramatically after the
      guarantee programs were implemented. To ensure the guarantees are met, additional
      nursing staff or ED beds may need to be added.

PMID- 12515112
TI  - EMATALA Q & A.

PMID- 12515113
TI  - [The effects of lipoproteins on human vascular endothelial gap junctional
      intercellular communication].
AB  - The effects of HDL, LDL and ascorbic acid on cultured human vascular endothelial
      gap junctional intercellular communication (GJIC) were observed using
      fluorescence recovery after photobleaching assay under confocal laser scanning
      microscopy in this study. The results showed that in culture, human vascular
      endothelial cells could produce functional gap junctions. The fluorescence
      recovery rates of the LDL group were 6.691 +/- 2.634, 4.153 +/- 2.125 and 2.441
      +/- 0.720 respectively; when these rates were compared with the control and with
      each other, significant differences were found(P < 0.05). When the fluorescence
      recovery rates of the HDL group and Vitamin C group were compared with the
      control, no significant differences were found(P > 0.05). The fluorescence
      recovery rates of the LDL + HDL group were 3.500 +/- 0.890, 4.339 +/- 1.126 and
      5.243 +/- 1.278(n = 15) respectively, when these rates were compared with the
      control and with each other, significant differences were found (P < 0.05). These
      suggested that LDL should be able to inhibit GJIC in human vascular endothelial
      cells, and the inhibition could be diminished by HDL or ascorbic acid. Inhibition
      of vascular endothelial GJIC may be one of the atherosclerogenic mechanisms of
      LDL, whereas HDL and ascorbic acid may be conducive to the improvement of
      endothelial GJIC. But it may also be only a compensatory behavior of endothelial
      cells to injuries.

PMID- 12515114
TI  - [Inhibition of the activation and collagen production of cultured rat hepatic
      stellate cells by antisense oligonucleotides against transforming growth factor
      beta 1 is enhanced by cationic liposome delivery].
AB  - In order to investigate the inhibition of the activation and collagen production
      of cultured rat hepatic stellate cells (HSC) by antisense oligonucleotides (ASON)
      against TGF beta 1 after cationic liposome (lipofectin) delivery, the authors
      synthesized a 20-mer phosphorothioate antisense oligonucleotide of TGF beta 1
      mRNA, and its sense of missense oligonucleotides, and then treated the HSC with
      cationic liposome/oligonucleotide complexes respectively. The cellular uptake of
      32P-labelled oligonucleotides was determined by liquid scintillation counting,
      and HSC activation was assessed by the expression of alpha-smooth muscle
      actin(alpha-SMA). The cellular uptake of lipofectin/32P-ASON complex was
      approximately five-fold higher than that of 32P-ASON alone. Cationic liposome
      (lipofectin) delivery significantly increased the inhibition of HSCs activation
      by ASON, while compared with the use of naked TGF beta 1 ASON at the same
      concentration (at a final concentration of 1 mumol/L, P < 0.05). However, these
      effects were not observed in lipofectin alone, liposome/sense or missense oligos
      complexes at the same concentration. The oligonucleotide or lipofectin/oligos
      complexes had no cytotoxicity to rat HSCs in culture. These findings suggest that
      cationic liposome is an effective vehicle to improve the delivery of ASON to rat
      HSCs in culture, and the cationic liposome/TGF beta 1 ASON complex may be useful
      for the treatment of hepatic fibrosis.

PMID- 12515115
TI  - [Expressional change of brain-derived neurotrophic factor in adult cat spared
      DRG].
AB  - This investigation was aimed to search the expressional change of BDNF in the
      normal and spared L6DRG. The L6DRGs from 20 adult male cats (5 normal cats, 15
      unilateral L6 spared roots cats allowed to survive 3 days, 6 days and 12 days
      respectively) were embedded in paraffin, using immunohistochemical reaction to
      detect BDNF. RESULTS: 1. Normal DRG neurons were divided into three
      categories(large, medium and small) with the cell body diameter 32 microns and 44
      microns as the dividing lines. 2. There are 50.87% BDNF positive neurons in
      normal L6DRG. After operation, the number of BDNF positive neurons of the
      operated side DRG significantly increased, especially 6 days(76.70%). Normal and
      postoperative BDNF positive neurons were mainly small neurons. After partial
      section of DRG, the expression of BDNF in spared DRG neurons increased, which
      might be involved in promoting collateral sprouting of spared root in spinal cord
      and rescuing the dorsal horn neurons from partial deafferentation.

PMID- 12515116
TI  - [Study of the distribution feature of the endocrine cells of human islet and its
      relation to microvasculature].
AB  - Double immunohistochemical stain was used for the study of distribution feature
      of the endocrine cells of human islets and its relation to the microvasculature.
      The results were as follows (1) Sheath islet was found in human adult islets and
      the B cells situated the central part of the islets and arrounding it were the A
      and D cells which formed the sheath of the islets. (2) The identical distribution
      of the A and D cells was found. (3) Some islets were divided into several
      "subunite" by connective tissue in which the B cells and A(or D) cells situated
      the central and peripheral part respectively. (4) The A and D cells were near the
      microvasculature. These results will provide morphologic basis for the research
      of the functional relation among the endocrine cells.

PMID- 12515117
TI  - [Studies on metal porphyrins as two-functional mimic of enzyme].
AB  - In this study, four metal porphyrins (tetraphenylporphyrinesulfonatoiron,
      tetraphenylporphyrinesulfon-atocopper, tetraphenylporphyrinesulfonatomanganese,
      and tetraphenyl porrphyrinesulfonatocobalt) were used as dual function mimicry of
      superoxide dismutase (SOD) and catalase (CAT). The first function, scavenging O2.
      , has been proved by using riboflavine-methionine photoreduction method in the
      concentration range of 10(-5)-10(-6) mol/L. The second function, scavenging H2O2,
      has been demonstrated by means of spectrophotometry, and the percentage of
      decomposing H2O2 increases with the concentration of the imitating compounds.
      Metal porphyrins, SOD and CAT were measured by the liver homogenate technique of
      mice and the results showed that they had obvious action of decreasing the lipid
      peroxidation. Tetraphenylporphyrinesulfonatomanganese was measured by isolated
      ischemia reperfusion heart of rats. The results indicated that the Mn-TPPS4 could
      reduce the damages of active oxygen and had evidently protective effects on
      isolated ischemia-reperfusion mocardium of rats.

PMID- 12515118
TI  - [Three-dimensional finite element analysis of all-ceramic crowns of the posterior
      teeth].
AB  - The all-ceramic crown has been applied in clinical practice for its esthetic
      value and excellent biocompatibility. The purpose of this study was to examine
      the effect of different cervical marginal shapes on the stress distribution of
      all-ceramic crowns of the mandibular first molar by three-dimensional finite
      element analysis. The results showed that under vertical loading, the bearing
      compress stress on the occlusal region, the tensile stress concentration were
      observed at buccal cervical marginal of all-ceramic crowns; the stress at the
      surface of the crown was the highest, the stress inside the crown was higher than
      that inside the prepared teeth; the shoulder's stress value was lower than the
      chamfer's. These results lay the theoretic foundation for clinical application of
      all-ceramic crown, suggesting that the shoulder design should be recommended in
      clinical practice when the all-ceramic crowns are planned. The cervical thickness
      of the crown should be within 0.5-1.0 mm, and the crowns surface should be
      polished well to improve its resistance to fracture.

PMID- 12515119
TI  - [The effects of mechanical stretching on DNA synthesis of human periodontal
      ligament fibroblasts].
AB  - This study was aimed at the effects of mechanical stretching on DNA synthesis of
      human periodontal ligament fibroblasts(PDLF). Flow cytometry(FCM) was used to
      examine the proliferative activities of PDLF grown on the flexible culture dishes
      subjected to mechanical stretching. The results showed that in the range of 0.5%
      8%, mechanical stretching could stimulate DNA synthesis 2 hours after the cells
      had been subjected to stretches. DNA synthesis reached the peak in the 6 hours.
      The effect of 2% stretching was more significant. As time went by, the mitogenic
      effect of stretch was decreased. These findings suggest that mechanical
      stretching can stimulate DNA synthesis of PDLF.

PMID- 12515120
TI  - [A comparative study of fatty acids in human dental plaque and whole saliva].
AB  - This study was intended to carry out qualitative and quantitative analyses of
      fatty acids in plaque and saliva. Samples of plaque and saliva from 10 volunteers
      were analyzed for fatty acids by gas-chromatography and gas-chromatography/mass
      spectrometry. The sample preparation procedure allowed specimens from individual
      volunteers to be analyzed. The results showed the plaque contained C14.0, C15.0,
      C16.0, C16.1, C18.0, C18.1, C18.2, C20.0 acids and the saliva contained C16.0,
      C18.0, C20.0, C16.1, C18.1, C18.2 acids. The concentration of fatty acids in
      plaque was 35.17 +/- 7.723 micrograms/mg (dry weight); and that in saliva was
      13.23 micrograms/ml. Quantitatively, C18.1 and C16.0 acids were the largest fatty
      acids. These findings imply that the origin and role of the fatty acids in plaque
      and saliva may be different.

PMID- 12515121
TI  - [A study of the immune in formation of calcium bilirubinate gallstones in
      different rabbit models--the changes of the immunoglobulins in serum and bile and
      the immunoglobulins forming cells in the gallbladder mucoderm].
AB  - The changes of Ig-forming cells in the gallbladder mucoderm and the
      immunoglobulins in serum and bile were studied in the rabbit models. One hundred
      rabbits were randomly divided into the control group (Con, n = 10), simple
      biliary obstruction group (BO, n = 45) and biliary obstruction and infection
      group (BOI, n = 45). The results showed that the concentrations of serum
      immunoglobulin A (IgA) in BO and BOI groups increased remarkably in all phases (P
      < 0.001), The concentrations of serum IgG in both groups increased with the
      formation of gallstones. The IgA and IgG contents of bile samples in BO and BOI
      groups with negative bacterial culture were much higher than those of control
      group (P < 0.05), but the Ig content of bile with positive culture was slightly
      lower than that of the control group. Only a few Ig-forming cells were found in
      the gallbladder mucoderm of normal rabbits. The counts of Ig-forming cells in the
      mucoderm in BO group remained unchanged, but increased much higher in BOI group
      (P < 0.001), especially in IgG formation. This experiment demonstrates the
      immunoglobulins of serum and bile change significantly during the formation of
      gallstones. The Ig content of bile has a relationship with bacterial infection.
      IgA plays an important role in gallstone formation. The gallbladder of rabbit may
      be an important place of Ig-formation. The quantity of Ig forming cells in
      biliary tract may have a close relationship with the gallstone formation.

PMID- 12515122
TI  - [Changes of lipoprotein lipase and hepatic lipase and their significance in
      gallstone formation in rabbit model].
AB  - This experiment was made to investigate the changes of lipoprotein lipase(LPL)
      and hepatic lipase (HL) activity and their effects on gallstone formation in
      rabbit model in which the stones were induced by high cholesterol diet.
      Activities of plasma LPL and HL were determined; other data including
      concentration of plasma lipoprotein cholesterol, concentration of bile
      cholesterol and bile acids were also obtained. The results showed that with the
      rabbits continuously fed on high cholesterol diet, LPL activity heightened
      markedly (P < 0.05), and HL activity increased gradually (3 and 4 weeks groups vs
      control group, P < 0.05). The changes of concentration of plasma VLDL-C and LDL-C
      were the same as that of LPL activity, but the concentration of plasma HDL-C,
      HDL2-C, HDL3-C and bile acids showed no significant changes (P > 0.05). These
      results suggest that the heightened activities of LPL and HL might make the liver
      take up more cholesterol, secrete it into the bile duct and hence accelerate
      gallstone formation.

PMID- 12515123
TI  - [The effect of adrenalectomy on morphine dependence behavior of rats with forced
      swimming].
AB  - In this study, the possible action of stress and glucocorticoids on the drug
      seeking behavior was explored in the rats with morphine dependence. Forty rats
      were assigned into four groups randomly and received different treatments as
      follows: adrenalectomy; adrenalectomy + hydrocortisone 20 mg/kg S.C.;
      adrenalectomy + hydrocortisone 40 mg/kg S.C.; saline S.C.; The effect of
      adrenalectomy and hydrocortisone on morphine conditioned place preference (CPP)
      in rats with forced-swimming was observed. The results showed: 1. there was no
      significant difference for the adrenalectomized rats' spending time between the
      morphine and saline-paired side during the test session (t = 1.84, P > 0.05), but
      obvious differences of time spent between the morphine and saline-paired side
      were observed among the other three groups (P < 0.05 or P < 0.01); 2. the time
      spent in the morphine-paired side of the adrenalectomized group significantly
      decreased, compared with those of the other three groups, and there was no
      difference for the time spent in the morphine-paired side among the groups of
      adrenalectomy + hydrocortisone 20 mg/kg S.C., adrenalectomy + hydrocortisone 40
      mg/kg S.C., and saline S.C.. These data suggested that adrenalectomy could
      decrease the facilitation action of morphine CPP induced by forced swimming in
      rats, whereas administration with glucocorticoids should reverse this effect.

PMID- 12515124
TI  - [Immune reconstitution in immunosuppressed pigs with human immune competent
      cells].
AB  - To reconstitute the immune system of the pig with human immune cells after
      destroying or suppressing it, so that the transplant immunoreactivity between
      human and pig could be monitored in vivo. Fifteen Chinese Neijiang pigs were
      divided into 3 groups. Group A (n = 5) received immunosuppression through
      intravenous infusion of methotrexate (MTX), myleran and cyclophosphamide (CTX).
      Group B received intraperitoneal injection of human bone marrow and spleen cells
      (HBSC) after the same treatment as group A. Group C (n = 5) received intravenous
      infusion of HBSC after the same treatment as group A. Blood routines and
      biochemical analysis were monitored. The chimerisms of human cells were
      supervised through immunohistochemistry of cytospin of peripheral blood from
      recipient pigs and flow cytometry of the same specimen and immunohistochemistry
      of frozen tissue sections and paraffin sections. All pigs in group A survived
      definitely. Group B and C survived 3 days to 54 days and 15 hours to 60 days
      respectively. The peripheral white blood cell count (WBCC) of group A, B and C
      decreased to the bottom 7 days after drug administration, about 1%-10% of the
      normal level. After transplantation, the WBCC of group B and C recovered more
      slowly than those of group A. Human cells were found in the recipient pigs of
      group B and C after transplantation through immunohistochemistry of peripheral
      blood cytospin and flow cytometry. Infiltration of human cells was found in the
      spleens and lungs of group C and D through immunohistochemistry. The chimerism of
      human cells in recipient pigs could be established by transplanting human bone
      marrow and spleen cells into immunosuppressed pigs. It is possible that XGVHD
      occurs in the recipient, which offers a novel animal model for studies on
      immunoreactivity of pig-to-human xenotransplantation. The proportions of human
      cells in peripheral blood of recipient pigs are low long after transplantation
      through both intraperitoneal injection and intravenous infusion.

PMID- 12515125
TI  - [Polymorphism of ACE gene and its relationship with serum ACE activity in the
      Hans in Chengdu region].
AB  - This study was aimed at the angiotensin converting enzyme (ACE) gene
      insertion/deletion(I/D) polymorphism distribution in Chinese and its relationship
      with serum ACE activity(SACE). SACE activity and ACE gene polymorphism in 90
      healthy persons in Chengdu region were investigated using a spectrophotometric
      assay and the PCR technique, respectively. The results showed that, in the Hans,
      DD genotype of ACE gene was 18%, DI genotype 44%, and II genotype 38%. Allele
      frequencies were 0.40 for the D allele and 0.60 for the I allele. There were
      significant relationships between ACE I/D polymorphism and SACE activity. The
      results suggest that ACE genotype distribution be different between races, that
      II genotype and I allele be more frequent in Chinese, and that SACE activity be
      under the influence of a genetic polymorphism of ACE in Chinese.

PMID- 12515126
TI  - [Biodistribution and metabolism of radio-iodinated IBZM in rats].
AB  - The aim of this study was to assess the bio-distribution and metabolic behavior
      of radio-iodinated IBZM in rats. Routine and improved technologies were used. The
      results showed that the radio-iodinated IBZM had favorable bio-distribution and
      metabolic behavior. The radio-distribution was high and the radio-iodinated IBZM
      remained long in striatum where no metabolic by-products manifested at 30 minutes
      after injection. These suggested that radio-iodinated IBZM is an excellent
      dopamine D2 receptor imaging agent for SPECT in humans, and it is stressed that
      thyroid must be blocked by iodine during the study of imaging.

PMID- 12515127
TI  - [The measurement of tracheo-bronchial mucociliary clearance by technetium-99m
      DTPA aerosol scintigraphy].
AB  - Mucociliary clearance of respiratory channels is one of the important mechanisms
      guarding against retention of foreign particles within the lungs. Thus objective
      assay of the system is essential to recognizing and understanding its
      abnormalities. In this study, 18 healthy subjects and 32 patients with chronic
      obstructive pulmonary diseases (COPD) were examined by technetium-99m-DTPA
      aerosol scintigraphy. Monitoring was performed by visual inspection
      (cinescintigraphy) and quantitative analysis. The mucociliary clearance rates of
      18 healthy subjects and 32 COPD patients were 3.89 +/- 0.92 mm/min and 1.32 +/-
      0.59 mm/min respectively. Statistical analysis indicated that the airway
      clearance rate and mucociliary clearance rate of COPD patients were significantly
      lower than those of normal subjects (P < 0.01). The method of assay reported here
      is simple and objective. It has not only the advantage of visual inspection and
      quantitative analysis, but also the potential usefulness in studying other
      bronchial diseases and evaluating therapeutic effectiveness of drugs.

PMID- 12515128
TI  - [Sulindac induced apoptosis of HT-29 colon adenocarcinoma cell].
AB  - This study was intended to examine whether sulindac induces apoptosis in the HT
      29 cells. Flow cytometry, transmission electron microscopy and DNA
      electrophoresis were used. Flow cytometry, transmission electron microscopy and
      DNA electrophoresis all demonstrated that sulindac could induce apoptosis of the
      HT-29 cell line in a time- and dose-dependent manner. After treatment with 0.3
      mmol/L, 0.6 mmol/L and 1.2 mmol/L sulindac for 48 hours, apoptotic cells in the
      treatment groups reached 5.8%, 7.6% and 11.7% versus 2.9% in the control group;
      after treatment for 72 hours, apoptotic cells in the treatment groups increased
      to 12.5%, 15.4% and 24.4% versus 5.1% in the control group, respectively, P <
      0.05. This study has demonstrated that colon adenocarcinoma HT-29 cell line can
      be induced by sulindac.

PMID- 12515129
TI  - [The relationship of cellular DNA content with clinical stage and biological
      features of colorectal cancer].
AB  - The purpose of this study was to explore the relationship of cellular DNA content
      with clinical stage and biological features of cancer. Flow cytometry was
      performed on fresh specimens from 86 patients from 1997 to 1998. Forty-five
      (53.3%) specimens were found to contain cells with abnormal DNA (DNA
      nondiploidy). Although none of the sex, age, site, differentiation variables
      correlated with flow cytometric DNA ploidy, nondiploidy was associated with
      Dukes' stage and lymph node metastasis. Duke's A stage tumors were more
      frequently diploid than were more advanced tumors, but no difference between
      Duke's B, C and D stages were observed. These findings suggest that ploidy is
      associated with some pathological factors.

PMID- 12515130
TI  - [The expression of cell adhesion molecules on lymphatic endothelial cells in
      rectum adenocarcinoma of human].
AB  - This study was conducted to explore the mechanism of lymphatic dissemination and
      metastasis of cancer cells; the specific aim was to investigate the expression of
      cells adhesion molecules on lymphatic endothelial cells. Immunohistochemical
      method was used. The rectum tissues and lymphnodes were taken from five normal
      human subjects. The cancer peripheral tissues and lymphnodes, and the
      metastasized lymphnodes were taken from eight patients with rectum
      adenocarcinoma. The result showed that the intercellular adhesion molecule-1
      (ICAM-1) and carcinoma embryonic antigen (CEA) were expressed on lymphatic
      endothelial cells in cancer peripheral tissues and metastasized lymphnode. The
      expression of ICAM-1 and CEA in cancer peripheral tissues and lymphnodes was much
      more remarkable than that in metastasized lymphnodes. These data suggest that
      ICAM-1 and CEA be cell adhesion molecules between cancer cells and lymphatic
      endothelial cells.

PMID- 12515131
TI  - [The relations of cellular DNA content to lymph node metastasis in gastric
      carcinoma].
AB  - The objectives of this study were to evaluate the relations of cellular DNA
      content, S-phase fraction (SPF) and G2/M-phase(G2/MPF) to lymph node metastasis
      in gastric carcinoma by using flow cytometry. The results showed that the
      incidence of lymph node metastasis and SPF were significantly higher in aneuploid
      carcinoma than in diploid carcinoma(P < 0.05). But the G2/MPF values did not
      correlate with lymph node metastasis. These findings suggest that correlations
      between cellular DNA content, SPF and the extent of lymph node metastasis are
      present.

PMID- 12515132
TI  - [The effect of intraperitoneal chemotherapy on retroperitoneal lymph node
      metastasis of ovarian cancer].
AB  - The objective of this study was to investigate the effect of intraperitoneal
      chemotherapy(repeated injections of cisplatin in small doses during a short time)
      on retroperitoneal lymph node metastasis of ovarian cancer. Thirty patients with
      ovarian cancer were selected and divided into two groups. The patients in the
      first group received intraperitoneal chemotherapy only once (48 hours before
      operation); the patients in the second group received intraperitoneal
      chemotherapy twice (96 hours and 48 hours before operation). After the
      intraperitoneal chemotherapy, according to the predicted time, the Pt
      concentrations of the tissues were measured by flameless atomic absorption
      spectrometry; the pathologic examinations of the lymph nodes were carried out.
      The results showed that the drug concentrations of the aortic, obturator and
      iliac lymph nodes of the first group were not significantly different, neither
      were the drug concentrations of the lymph nodes of the second group. The drug
      concentrations of the lymph nodes of the first and the second groups were 2.06
      and 1.91 times that of the surrounding tissues respectively. Also, the drug
      concentrations of peritoneum of the first and the second groups were 4.14 and
      2.50 times that of the lymph nodes. The drug concentrations of the iliac,
      obturator and aortic lymph nodes of the second group were 2.27, 2.75 and 2.54
      times that of the first group (P < 0.005). Under light microscope, the metastatic
      cancer tissues in lymph nodes showed liquefaction necrosis in the second group.
      The results indicate that small doses of cisplatin given by repeated injections
      during a short time can lead to drug accumulation and consequently high efficacy
      with low toxicity, suggesting that this method may be used for the treatment of
      lymphatic metastasis of ovarian cancer.

PMID- 12515133
TI  - [Study on sensitivity of neuroglioma to chemotherapeutic drugs].
AB  - In this study, the chemosensitivity of 36 cases' fresh neuroglioma specimens was
      examined in vitro with MTT assay. The separation method for single tumor cell,
      the number of planting of cells, and the dosage and acting time of drugs, which
      have effects on the results of MTT assay, were studied systematically. On the
      basis of this experiment, we established a screening method for the
      chemosensitivity of neuroglioma; it is accurate, rapid, and simple. At the same
      time, the results showed that neuroglioma was more sensitive to the
      chemotherapeutic drugs Vm26, DDP and MMC, and the sensitivity varied with not
      only the drugs but also the individuals.

PMID- 12515134
TI  - [Expressions of apoptosis-associated proteins in prostate carcinoma and their
      clinicopathological significance].
AB  - This study was made to explore the expressions of P53, P16, Bc1-2 and Bax protein
      in prostate carcinoma and their relations to histopathological grading, clinical
      staging and prognosis of this tumor. Immunohistochemical staining method was used
      to assess the expression of P53, P16, Bc1-2 and Bax protein in 51 cases of
      prostate carcinoma. The positive rates of P53, P16, Bc1-2 and Bax proteins were
      31.37%, 54.90%, 21.57% and 74.51% respectively. The expression of P53 and Bc1-2
      showed positive correlation with the histopathological grading and clinical
      staging of this tumor (P < 0.05). However, the expression of P16 and Bax showed
      negative correlation with the grading and staging of the tumor (P < 0.05). The
      expression of P53 protein correlated with the survival rate of these patients.
      There was a relation between P53 and Bc1-2, and a relation between Bc1-2 and Bax
      also (P < 0.05). These findings suggest that expressions of P53, P16, Bc1-2 and
      Bax may be helpful to the grading, staging and prognostic evaluation of prostate
      carcinoma.

PMID- 12515135
TI  - [Evaluation of side-effects after 131I-therapy for differentiated thyroid
      carcinoma].
AB  - The purpose of this study was to evaluate the side-effects of differentiated
      thyroid carcinoma after treatment with 3.7-7.4 GBq of 131I. A total of 342
      patients were treated with 131I from May, 1989 to January, 1999. The acute side
      effects, the short-term and long-term side-effects were analyzed. The follow-up
      lasted 1-10 years with an average of 5.4 years. The results showed that
      thyroiditis occurred predominantly in the patients with a rate of 131I uptake >
      30%, whereas sialoadenitis occurred more prevalently in the patients with a rate
      of 131I uptake < 30% (P < 0.001). The rates of nausea, vomiting, diarrhea and
      gastralgia were 12.2%, 5.2%, 3.5% and 2.7% respectively. There were no
      significant changes in the hemogram after treatment, compared against that before
      treatment. The overall rates of transient platelet abnormalities and leukopenia
      were 10.4% and 4.0% respectively, but the rates of the abnormalities in the
      patients with cumulative doses of 131I > 18.5 GBq were significantly higher than
      those in patients with cumulative doses of 131 I < 18.5 GBq. The lower rate of
      acute and short-term side-effects and the absence of long-term side-effects in
      this study indicate that 131I can be safely used to treat differentiated thyroid
      carcinoma.

PMID- 12515136
TI  - [Preliminary isolation and identification of neurotrophic factors sensory neurons
      in spinal dorsal horn of embryonic chicken].
AB  - Our previous studies have demonstrated that the extract from dorsal horn of
      embryonic chicken can promote apparently the neurite growth of spinal ganglion
      during development. In this study, we investigated progressively the neurotrophic
      factors for primary sensory neurons in spinal dorsal horn. The tissues of spinal
      dorsal horn from five hundred Hamburger Stage-40 embryonic chickens were taken.
      After homogenization and centrifugation, the supernatant was subjected to SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) for analyzing the protein in dorsal
      horn. The simple protein band fishing by cell (SPBFC) technique was employed in
      finding the protein bands with neurons attached, and then such protein bands,
      were taken and transferred to nitric cellulose paper for Western hybridization
      analysis by antibody for NGF, BDNF, NT-3 and GDNF respectively. The results of
      SPBFC showed that some neurons were attached to gel within the scope of mobility
      relative front (Rf) 0.10-0.19, 0.30-0.35, 0.50-0.55, 0.60-0.67 and 0.90-0.94
      respectively, indicating there were some neurotrophic factors for maintaining
      neuron survival in the above Rf scope. Moreover, the result of Western
      hybridization showed that the positive hybridization bands in each scope were
      that of NGF, BDNF, GDNF; NGF, BDNF, NT-3; NGF, BDNF, NT-3; NGF, NT-3 and BDNF, NT
      3 respectively; indicating that the neurotrophic effect of spinal dorsal horn
      tissue on primary sensory neurons involves NGF, BDNF, NT-3 and GDNF. These also
      suggest that the neuronal survival effect in each Rf scope involves at least two
      or more neurotrophic factors.

PMID- 12515137
TI  - [Morphological observation on dorsal root ganglion neurons of embryonic chicken
      in vitro].
AB  - The aim of this study was to explore the developmental character of neurons from
      dorsal root ganglion (DRG) of embryonic chicken in vitro. The DRG neurons of
      Hamburger stage 35 were cultured and prepared at 0, 1, 2, 3, 4, 5, 7, 14 and 21
      days respectively. The number of neuronal survival was counted at each cultured
      stage (observed area: 2.5 x 10(5) microns 2) and the morphological change of
      neurons in vitro was observed and compared with that of neurons in vivo. The
      results showed the counts of neuronal survival were 94 +/- 4, 83 +/- 6, 67 +/- 4,
      65 +/- 7, 68 +/- 5, 71 +/- 9, 73 +/- 6, 22 +/- 4, and 0 respectively; the
      cultured neuronal shape during 48 h incubation was mainly oval or sphere, similar
      to that of neurons in vivo. However, the shape of some neurons changed into cone
      or shuttle after three days incubation, while the neuronal shape in vivo did not
      change. These findings indicate that only some of neurons can survive and grow
      and the lifetime is limited in vitro, on the other hand, the developmental
      character of neurons in vitro may be different from that of neurons in vivo.

PMID- 12515138
TI  - [Terminal differentiation of human acute promyelocytic leukemia (APL) cells
      induced by Tanshinone II A in primary culture].
AB  - The aim of this study was to investigate whether Tanshinone II A (Tan II A) can
      induce human acute promyelocytic leukemia (APL) cells to differentiate or not in
      primary culture. The APL cells from 5 cases were cultured respectively with Tan
      II A at the concentration of 0.5 microgram/ml for 7 days in vitro. The
      differentiations of these leukemia cells were observed cytomorphologically and
      examined by nitroblue tetrazolium (NBT) test. The cell DNA cycle and membrane
      cluster differentiation (CD) antigens (CD33, CD11b) were analyzed by flow
      cytometry. The results showed that 82.5% +/- 4.8% of APL cells were induced into
      morphologically and functionally differentiated cells. The cell growth curve
      showed that the growth of APL cells was inhibited. The degree of differentiation
      and growth inhibition induced by Tan II A was not different from that by ATRA (P
      > 0.05). Flow cytometry analysis showed that Tan II A arrested APL cells in G0/G1
      phase and inhibited cellular DNA synthesis. This study demonstrates that Tan II A
      can induce differentiation of APL cells in vitro, and hence it is worthy of
      further studies for clinical use.

PMID- 12515139
TI  - [An experimental study combined on traditional Chinese medicine with
      immunosuppressant for treatment and prevention of tubular interstitial
      nephritis].
AB  - The objective of this study was to determine the effect of Chinese herbs and
      immune inhibitors on diffuse proliferative glomerulonephritis. The tubular
      interstitial infiltration of cell, TGF-beta expression and interstitial fibrosis
      were investigated, and the relationship between clinical data and pathological
      changes was analysed. The results showed the infiltration of cells was inhibited
      in the "Chinese herbs combined with prednisone" group, the infiltration of cells,
      TGF-beta expression and interstitial fibrosis were all inhibited in the
      cyclophosphamide and prednisone" group. But in the prednisone group, interstitial
      fibrosis was not inhibited. These data suggest that the combined use of Chinese
      herbs, immunosuppressant and prednisone can inhibit the interstitial cell
      infiltration and prevent the interstitial fibrosis in diffuse proliferative
      glomerulonephritis.

PMID- 12515140
TI  - [Preliminary echocardiographic evaluation on prosthetic valve replacement of
      preserving the subvalvular apparatus with artificial chorade for mitral
      stenosis].
AB  - The purpose of this study was to evaluate the preliminary results after
      prosthetic valve replacement of preserving the subvalvular apparatus with
      artificial chorade for mitral stenosis. 20 patients had received operation with
      expanded polytetrafluoroethylene(e-PTFE) as artificial chordade. The patients
      were followed up by means of echocardiography. The time of follow-up study varied
      from 4 to 18 months with a mean of 6 months. The left atrial, ventricular
      dimension as well as ventricular function were assessed. In addition, the length
      of artificial chorade and obstruction of left ventricular outflow track were
      observed. The results showed that left atrial diameter (LAD, from 57.59 +/- 13.51
      mm to 47.05 +/- 9.55 mm), left ventricular end-diastolic dimension (LVEDD, from
      46.23 +/- 12.56 mm to 42.41 +/- 10.86 mm), left ventricular end-systolic
      dimension (LVESD, from 33.50 +/- 10.20 mm to 29.68 +/- 8.40 mm) decreased (P <
      0.01), and ejection fraction (EF, from 52.59 +/- 11.89% to 58.36 +/- 8.03%)
      increased (P < 0.05) after operation. There were no significant changes of
      fractional shortening (FS, from 29.23 +/- 8.99% to 31.05 +/- 6.08%). The length
      of artificial chorade ranged from 2.6 cm to 4.3 cm (the mean, 3.2 cm). There was
      no case of obstruction of left ventricular outflow track. It is believed that the
      result of preliminary echocardiographic observation on prosthetic valve
      replacement of preserving the subvalvular apparatus with artificial chorade for
      mitral stenosis is satisfactory.

PMID- 12515141
TI  - [Study of spontaneous echo contrast in patients with rheumatic mitral stenosis by
      transesophageal echocardiography].
AB  - Spontaneous echo contrast (SEC) is common in the areas of slow blood flow. This
      study was conducted to examine the correlation of SEC and left atrial appendage
      function, atrial fibrillation (Af) and thrombus in patients with rheumatic mitral
      stenosis. The transthoracic and multiplane transesophageal echocardiograms were
      performed on 117 patients(mean age 42.22 +/- 10.79 years). Left atrial size, left
      atrial appendage area, mitral valve area, left atrial appendage flow peak
      emphatic velocity and full velocity were measured. The presence of SEC and
      thrombus in the left atrium and appendage was noted. The results showed that
      among the patients, 57 had normal sinus rhythm, 60 had Af; 19 had thrombus, 98
      had no thrombus; 71 had SEC and 46 had no SEC. Compared with the patients without
      SEC, the patients with SEC showed greater incidence of thrombus (28.76% vs 0, P <
      0.05), higher rate of Af (69.01% vs 23.91%, P < 0.05), larger LAD (46.93 +/- 0.85
      mm vs. 41.76 +/- 1.05 mm, P < 0.05), larger LAA area (8.06 +/- 0.32 cm2 vs 6.92
      +/- 0.31 cm2, P < 0.05), smaller MVA area (1.07 +/- 0.23 cm2 vs 1.32 +/- 0.35
      cm2, P < 0.05), lower LAA flow peak emphatic velocity (0.17 +/- 0.01 m/s vs 0.32
      +/- 0.02 m/s, P < 0.05), and lower LAA full velocity (0.18 +/- 0.01 m/s vs 0.31
      +/- 0.03 m/s, P < 0.05). These findings indicate that the presence of SEC is
      associated with significantly greater incidence of thrombus, higher rate of Af,
      larger LAD and LAA area, smaller MVA area, lower LAA flow peak emphatic velocity
      and full velocity. Atrial fibrillation, the diameter of left atrium and the area
      of mitral valve are independent predictors of SEC. SEC is significantly
      associated with LAA function and thrombus formation.

PMID- 12515142
TI  - [Analysis on 2158 neural tube defects diagnosed prenatally by ultrasound
      examination].
AB  - A retrospective survey was made to study the prenatal diagnosis on neural tube
      defects(NTD) by ultrasound examination from 1990 to 1993 in China. A total of
      2158 livebirths and stillbirths affected by NTD with 28 weeks or more of
      gestation were investigated in 233 hospitals of 28 provinces, municipalities and
      autonomous regions all over the country. The results showed that 61.8% of the NTD
      were diagnosed prenatally, and 56.5% of the NTD were diagnosed by ultrasound
      examination. The ratios of anencephaly, myelocele and meningocele diagnosed
      prenatally by ultrasound examination were 66.7%, 62.5% and 52.5% respectively.
      Thoracic(46.4%) and lumbar (43.4%) spina bifida were diagnosed more frequently
      than cervical(35.5%) and sacral(31.7%) spina bifida. The ratios of prenatal
      diagnosis on NTD by ultrasound examination in provincial, municipal, county, and
      factory hospital units were 55.7%, 59.4%, 49.0% and 57.2% respectively. The
      ratios of prenatal diagnosis of NTD by ultrasound examination from 1990 to 1993
      were 53.5%, 55.8%, 60.7% and 54.7% respectively. There was an increase in the
      prenatal diagnosis of NTD by ultrasound examination from 1990 to 1993. The ratios
      of prenatal diagnosis of NTD in county hospitals by ultrasound examination were
      relatively low. Anencephaly, myelocele and meningocele were more frequently
      diagnosed by prenatal ultrasound examination.

PMID- 12515143
TI  - [The correlation between anticardiolipin antibodies and disease activity in
      patients with systemic lupus erythematosus].
AB  - This study was conducted to determine the prevalence and clinical association of
      anticardiolipin antibodies (ACA) in serum of patients with systemic lupus
      erythematosus (SLE). ACA (IgG, IgA, IgM) was measured by enzyme-linked
      immunosorbent assay (ELISA) in the serum sample of 87 patients of SLE. The
      prevalence rates of ACAIgG, ACAIgA and ACAIgM were 62.1%, 52.9% and 35.6%
      respectively. The titers of ACAIgG and ACAIgM were positively correlated with the
      disease activity (r = 0.2763, P = 0.044; r = 0.3294, P = 0.018); ACAIgG, ACAIgA
      and ACAIgM were negatively correlated with complement C3 (r = -0.4737, P = 0.000;
      r = -0.2990, P = 0.017; r = -0.2758, P = 0.029); and ACAIgG was negatively
      correlated with complement C4 (r = -0.4079, P = 0.005). The titers of ACAIgA in
      patients with thrombosis was higher than that in patients without thrombosis. The
      patients with central nervous system involvement (CNS-SLE) had significantly
      higher ACAIgG and ACAIgM titers, compared with those without CNS-SLE. The results
      indicate there is a correlation between ACA titers and disease activity. In
      patients with thrombosis, the titer of ACAIgA is higher, and in patients with CNS
      SLE, the titers of ACAIgG and ACAIgM are higher.

PMID- 12515144
TI  - [The study on the anti-osteoporosis effect of clodronate in ovariectomized rats].
AB  - To evaluate the anti-osteoporosis effect of clodronate in ovariectomized rats, 44
      female Wistar rats, aged 8 months, were divided randomly into 4 groups: the SHAM
      group (subjected to sham operation); the OVX group (subjected to bilateral
      ovariectomy); the E3 group (subjected to bilateral ovariectomy and treated after
      surgery with nilestriol 1 mg/kg BW by gavage once a week for 12 weeks), and the
      clodronate group (subjected to bilateral ovariectomy and treated after surgery
      with clodronate 5 mg/kg BW by subcutaneous injection twice a week for 12 weeks).
      All the animals were sacrificed 12 weeks after the operation. The blood and urine
      samples were collected for determination of biochemical indices. The humeri and
      tibiae were prepared for determination of net weight, ash weight, calcium and
      phosphorus content, bone density, as well as bone histopathology and
      histomorphometry. The left femora were processed for bone anti-curve power. The
      results showed that as compared with the SHAM group, the net weight, ash weight,
      calcium content, density and anti-curve power of bones, te trabecular bone volume
      and thickness were all significantly reduced in the OVS group, while its
      osteoblast index, osteoclast index and urine hydroxyproline content were
      obviously close to normal levels. The data indicates that both clodronate and E3
      can effectively prevent bone loss in ovariectomized rats.

PMID- 12515145
TI  - [Effects of YMB injection on hemorheology in rats].
AB  - This study was designed to elucidate the mechanism of YMB Injection on anti-CAD
      therapy. Fufang Danshen Injection was used as positive control and saline was
      taken as negative control to study the effects of traditional medicine YMB
      Injection on hemorheological parameters in normal rats and hypostasis rats. The
      results showed YMB Injection had no effect on hemorheological parameters of
      normal rats, but it could effectively decrease whole blood viscosity and whole
      blood reduction viscosity of hypostasis rats. The data implied that YMB Injection
      could decrease blood viscosity and hence improve blood supply of the graft in
      anti-CAD therapy.

PMID- 12515146
TI  - [Quantification analysis of vascular endothelial cells in human solid tumor].
AB  - Angiogenesis is essential for the growth and metastasis of solid tumors.
      Intratumoral microvessel count, which represents a measure of tumor angiogenesis,
      has been associated with prognosis of patients with a variety of malignancies.
      But till now, it is still a problem to quantitate the angiogenesis of tumors
      exactly. In this study, the endothelial cells in 20 solid tumors were conjugated
      with anti-CD34 monoclonal antibodies labelled with red-fluorescent substances,
      and were observed by fluorescence microscopy and quantitated by flow cytometry.
      The results of flow cytometry were analysed by t-test. The correlation was
      analysed between percentage of flow cytometry and vessel counts (light
      microscopy, x 200) in each tumor which was stained with anti-CD34 monoclonal
      antibodies and anti-VIII factor related antigen polyclonal antibodies by using
      immunohistochemistry. The results showed there was significant difference between
      the treatment group and control group in flow cytometry, and a significant
      correlation between the endothelial cells percentage by flow cytometry and the
      vessel counts by immunohistochemistry was observed, although the average vessel
      counts were approximately three times with CD34 staining as much as with VIII
      factor related antigen staining. These data indicate that flow cytometry as a
      novel method can quantitate angiogenesis of tumors exactly and quickly.

PMID- 12515147
TI  - [Relationship between the changes of serum free fatty acids and insulin
      resistance in type 2 diabetics].
AB  - The purpose of this study was to investigate the changes of serum free fatty
      acids (FFA) in fasting state and absorptive state and the relationship between
      FFA changes and insulin resistance in the patients with type 2 diabetes (DM2). 75
      g of glucose were given to 60 patients with DM2. Fasting serum FFA, serum insulin
      levels and the same parameters 2 h after glucose load were measured by
      calorimetric and RIA methods. Fasting and 2 h after oral glucose tolerance test
      (OGTT) plasma glucose(PG) levels were also assessed by using glucose oxidase
      method. The results showed the levels of serum FFA, PG and insulin of fasting and
      after glucose load in the patients were significantly increased and their insulin
      sensitive (ISI) was remarkably decreased as compared with those in 30 normal
      controls, P < 0.05. Multiple stepwise regression analysis showed that the FFA
      level of 2 h after OGTT was negatively correlated with ISI, P = 0.0304. The
      results suggest that in patients with DM2, the levels of fasting and absorptive
      FFA are significantly elevated, which is negatively correlated with the decline
      of ISI, implying the association of abnormal fasting and absorptive FFA and
      insulin resistance in patients with type 2 diabetes.

PMID- 12515148
TI  - [Evaluation on usage of serum troponin-I, CK-MBmass and myoglobin measurements in
      diagnosing acute myocardial infarction].
AB  - The purpose of this study was to search the sensitivity of three indicators in
      early diagnosis of acute myocardial infarction (AMI) and analyze their window
      time duration in serum, along with the decision on experimental golden indicator
      in later AMI inspection and effect assessment after recovery by testing the
      concentrations of CTnI, CK-MBmass and Mb in AMI patients' serum. By using
      corpuscle chemiluminescence, the serum concentrations of CTnI, CK-MBmass and Mb
      in AMI patients, UA (unstable angina) patients, SM (skeletal muscle) patients and
      a normal group were assayed and compared. A dynamic analysis was followed in five
      periods, which separately focused on 3-5, 8-14, 20-24, 72 hours and 7 days after
      heart aching occurred in AMI patients. The results showed the positive rates of
      CTnI, CK-MBmass and Mb in AMI patients were 65%, 70% and 70% respectively, and
      the positive rate of CTnI in UA and SM groups was 0%. The CTnI, CK-MBmass and Mb
      values in group AMI were significantly higher than those in groups of UA and SM.
      Separately, the CTnI value in AMI was 84 and 91.63 times (the CTnI values) in UA
      and SM; the CK-MBmass value in AMI was 8.82 and 4.67 times and the Mb value in
      AMI was 11.57 and 2.25 times as high as those in UA and SM. Significant
      difference was observed by the comparison between AMI group and UA, SM groups (P
      < 0.001). According to the dynamic analysis, CTnI, CK-MBmass and Mb rose
      significantly at the early stage of AMI onset (3-5 hrs), and then gradually
      increased with time. The climax occurred in the period of 8-14 hrs and Mb
      returned to its normal state in 72 hrs. On the 7th day, CTnI still existed in
      serum, but CK-MBmass approximated to normality. In conclusion, these data
      demonstrate a relatively high sensitivity of CTnI, CK-MBmass and Mb in early
      diagnosis of AMI. CTnI is specific to cardiac muscle for its special positive
      rate. Also, CK-MBmass and Mb are of higher clinical value in diagnosing cardiac
      muscle damage. CTnI has the longest window-time, which makes it the best special
      indicator for terminal inspection and recovery decision on AMI.

PMID- 12515149
TI  - [The change in placental estradiol-progesterone ratio and its relationship with
      the fetal membrane's response to IL-1 beta in labor].
AB  - This study was designed to investigate the local changes in the levels of
      placental estradiol and progesterone and their ratio during term labor and to
      determine whether the PGE2-generating ability of the fetal membrane in response
      to IL-1 beta at term labor is greater than that at term not-in-labor. Forty
      pregnant women were divided into two groups: term labor and term not-in-labor.
      Placental estradiol and progesterone were measured by radioimmunoassay. The
      levels of fetal membrane PGE2 were measured by enzymoimmunoassay. The results
      showed that the placental concentration of estradiol and progesterone remained
      unchanged at the onset of labor, but the ratio of estradiol to progesterone
      increased significantly (P < 0.05). IL-1 beta stimulated fetal membrane to
      produce more PGE2 at term labor, and at term not-in-labor, too. But the increment
      of PGE2 generated by fetal membrane at term labor was greater than that at term
      not-in-labor. It is concluded that the change in placental estradiol to
      progesterone ratio may play an important role in the initiation of labor by
      altering the PGE2-generating ability of fetal membrane in response to cytokines.

PMID- 12515150
TI  - [Response to milrinone treatment in patients with chronic congestive heart
      failure].
AB  - The objective of this study was to examine the efficacy of milrinone in chronic
      congestive heart failure. In this randomized, double-blind, placebo-controlled
      trial, 30 patients with class III or IV chronic congestive heart failure were
      randomly assigned to receive milrinone (n = 15) or placebo (n = 15). The results
      showed that in the milrinone group, stroke volume increased from 38.50 +/- 5.34
      to 64.93 +/- 6.46 ml (P < 0.001), cardiac output increased from 3.39 +/- 0.42 to
      5.28 +/- 0.55 L/min (P < 0.001), cardiac index increased from 2.01 +/- 0.42 to
      3.21 +/- 0.57/min/m2 (P < 0.001) and ejection fraction increased from 0.23 +/-
      0.05 to 0.35 +/- 0.06(P < 0.001). In the placebo group, no hemodynamic effects
      were found. Milrinone favourably influenced the symptoms and heart function in
      11/15(73.3%) patients. In the placebo group, only 4/15(26.7%) patients had such
      response (P < 0.05). These data indicate that milrinone is effective for
      improving the hemodynamics status and heart function in patients with chronic
      heart failure.

PMID- 12515151
TI  - [Relationship between vulvar dystrophy, malignant tumor and the estrogen
      progestin receptor].
AB  - In order to investigate the relationship between vulvar dystrophy, malignant
      tumor, and estrogen, progestin receptor, we made an analysis on estrogen and
      progestin receptor (ER, PR) contents in 31 cases of vulvar dystrophy and 19 cases
      of malignant tumor, using the dextran-coated charcoal method. The Results showed
      that ER content of the mixed type was higher than that of the atrophic type. PR
      content of the mixed type was higher than that of the hyperplastic type; and the
      PR content of the hyperplastic type was higher than that of the atrophic type.
      The relationship between ER and PR contents of the vulvar dystrophy and adjacent
      normal tissue was in positive correlation. The PR content of vulvar squamous cell
      carcinoma went down along with the drop of its dedifferentiation degree. The PR
      content of carcinoma was much lower than that of the adjacent normal tissue. The
      results of suggest that the study provided theoretic basis for endocrinotherapy
      of the vulvar dystrophy, PR in malignant tumor is regarded as one of the indexes
      to predict prognosis.

PMID- 12515152
TI  - [A study on the shape of nose of the Jingpo people in China].
AB  - The objective of this survey was to provide data for clinical plastics of nose,
      medical aesthetics and cosmetology, anthropology, nationality study and medical
      jurisprudence. We carried out a somatological survey on the nose of 611 Jingpo
      people living in Yunnan. The survey covered 277 males (aged 15 to 60 years) and
      334 females (aged 13 to 55 years). The findings of the features of nose are as
      follows: the Nasal Root Height is high (average 55.83%); the Nasal Tip Direction
      is forward (average 81.17%); the Nasal Base is horizontal (average 79.17%); the
      Alae Nasi is slightly projecting (average 91.83%); the Nasal Profile is straight
      (average 74.83%). The type of the Nasal Index is middle (70.0-84.9). The average
      of the Nasal Height (NH) of both male and female is 49.09 mm, the average of the
      Nasal Length (NL) is 41.99 mm, the average of the Nasal Breadth (NB) is 36.44 mm,
      the average of the Nasal Index is 74.93, but there is significant difference
      between male and female. The average of the Nasal Depth (ND) is 14.59 mm, the
      average of the Nasal Deep Index is 40.19; there is no significant difference
      between male and female. There is no difference between adults and youths, but
      there is marked difference between adults and teenagers, suggesting that the
      development of the nose of the Jingpo people tends to end up in youth.

PMID- 12515153
TI  - [Establishment and application of a computerized radiography cephalometrics
      system].
AB  - We have developed a new-typed computerized radiography cephalometrics and
      prediction system. It includes cephalometrics, growth prediction,
      orthopedics/orthodontics prediction and profile prediction. In this study, 47
      lateral cephalograms were randomly selected to process a reliability test. The
      results showed the two groups were in agreement on all of the 25 measurement
      index. The system is easier, quicker and less prone to error than traditional
      cephalometrics approach. It is convenient for orthodontists.

PMID- 12515154
TI  - [Methodological study on preparation of a novel myocardial perfusion imaging
      agent: 99mTc-Q3].
AB  - This study was intended to explore the methods of preparing technetium-99m-N, N'
      ethylenebis (acetylacetoneiminato) bis [tris (3-methoxy-1-propyl) phosphine]
      (99mTc-Q3) as a newer cationic myocardial perfusion imaging agent. The optimum
      scheme of technetium labeling on the basis of exploring the effects of
      differently labeled conditions on radiochemical purity was established by a
      multivariate orthogonal experimental design. A newer agent for myocardial
      perfusion imaging was developed based on the optimum scheme by a stannous
      chloride reduction method. Preparation, separation, purification and quality
      control were performed by a chromatography. Experiments for stability (in vitro),
      sterility, apyrogen, safeness, and for imaging in animals were carried out.
      "A2B2C2" was chosen as the optimum scheme of this labeled complex. There each of
      A, B and C factors has significant effect on the radiochemical purity, and there
      is no one-class cross effect on the radiochemical purity between them. The
      labeling efficiency and radiochemical purity were measured over 99% labeled 10
      min later (at R. T.). The stability (in vitro) was good and kept up to 4 hr or
      testing (range: 92%-99.37%). The prepared product was sterile, apyrogenic and
      safe. The scintigraphic imaging in rabbits demonstrated that the tracer
      accumulated early in the heart and the myocardial imaging displayed clearly up to
      3 hr. The results of this methodological study demonstrate that not only high
      quality 99mTc-Q3 can be obtained but also a standardized procedure for labeling
      all kinds of 99mTc-agents can be set up, and on this basis, the one-step kit of
      99mTc-Q3 may be developed.

PMID- 12515155
TI  - [An adenosine triphosphate bioluminescence assay for detecting the number of
      living cells].
AB  - The method for detecting the number of living cells was studied. Using an
      adenosine triphosphate (ATP) bioluminescence assay, the present authors reported
      a perfect linear relationship between lg ATP concentrations and lg luminescence
      counts (r = 0.9963) as well as a relationship between lg number of cells and lg
      ATP luminescence counts (r = 0.9922). The detectable cells ranged from 10(2) to
      10(6) cells/ml, the coefficients of variation 1-3%. This method is simple,
      accurate and sensitive and has a high reproducibility.

PMID- 12515156
TI  - [Application of model 4650 type I compressor atomizer in bronchial challenge
      test].
AB  - This study was directed to the feasibility of applying a simple atomizer-model
      4650 type I (abbrev. M)-to bronchial challenge test. 92 cases of asthma were
      divided into 3 groups randomly. All of them were subjected to the bronchial
      challenge test by M atomizer, and by standard Dosimeter atomizer (abbrev. D) as a
      comparison. In the test by M atomizer, the times for inspiring challenging
      medicine were 1, 1.5 and 2 minutes for the 3 groups respectively, while the time
      for D atomizer was 1 minute for all. The results showed no significant
      differences (P > 0.2-0.5) between the two atomizers in the 3 groups, their values
      were linear correlated. When the inspiring time was 1 minute for both M and D,
      the test needed a higher concentration of challenging medicine for M than for D,
      their coefficient of correlation (r = 0.285) was relatively low. When inspiring
      time postponed to 1.5 minute for M, the difference in medicine concentration
      between M and D was smallest (-0.075 g/L), r = 0.665. However, a further
      postponed inspiring time to 2 minute for M reversely broadened their difference.
      These results indicated that the efficiency of M atomizer was a little lower than
      that of D, postponing the inspiring time for M could make up this weakness. A 1.5
      minute inspiring time for M atomizer was the suggestion. Some modifications on M
      atomizer were done by us for a better efficiency, and the cheap and popular M
      atomizer could be a good replacement in bronchial challenge test.

PMID- 12515157
TI  - [A simple biostatistical method for meta analysis of the data on 2 x 2 table].
AB  - Meta-analysis is a method in common use for data analysis in evidence-based
      medicine. In this paper, based on the Mantel-Haenszel and Peto methods used for
      Meta-analysis of the data on 2 x 2 table, we put forward a simple calculating
      method for clinicians. It is useful for Meta-analysis and can be easily applied
      to analysis of the data from multi-studies in evidence-based medicine.

PMID- 12515158
TI  - [Application of less-than-one-hour in situ hybridization to diagnosis of
      infectious agents].
AB  - Less-than-one-hour in situ hybridization manual method for immunocytochemical
      analyses of formalin-fixed, paraffin embedded tissue sections was used to detect
      infectious agents. The method employs capillary action to sequentially apply,
      incubate and remove liquid reagents from opposite pairs of glass microscope
      slides and allows for simultaneous immunocytochemical analyses. We used this
      method to detect EB virus in nasopharyngeal tissues and human papilloma virus in
      cervical tissues. This rapid and sensitive procedure represents a significant
      improvement for clinical immunocytochemical and research laboratories alike.

PMID- 12515159
TI  - [Antisense oligodeoxynucleotide targeted at the pre-s region of DHBV could
      inhibit virus replication in vivo].
AB  - To study the antiviral effect of antisense oligodeoxynucleotide (AS-ODN), AS-ODN
      phosphotioates targeted to DHBV Pre-S region (951-968nt) (5'-TATCTCCTCCATTGTTTG
      3') was synthesized. Two day-old ducklings were infected i.p. with 150
      microliters of DHBV (3 x 10(8) copies/ml DHBV). After 12 days, 6 DHBsAg and DHBV
      DNA positive ducks were divided into two groups. In treated group, each duck was
      injected i.v. AS-ODN 20 micrograms/gram weight/day for 10 dyas successively,
      while in the control group, each duck received the same volume of normal saline
      for 10 days. Sera from ducks prior to treatment and treated after 6, 10 days were
      collected, and after 10 days ducks were sacrificed and livers were examined.
      DHBsAg was significantly decreased in all three treated ducks after 10 days of AS
      ODN treatment. One of these ducks showed decreased DHBsAg even 6 days after
      treatment. Two out of three treated ducks showed decreased serum DHBV DNA, while
      one remained unchanged. In contrast, none of the control group showed decreased
      DHBsAg and DHBV DNA did not change. By Southern blot, DHBV DNA in the liver
      significantly decreased in 2/3 of the treated ducks and decreased in the other
      duck. In all control ducks, DHBV DNA remained strongly positive. Data indicated
      that AS-ODN targeting at Pre-S region could partly inhibit the replication of
      DHBV.

PMID- 12515160
TI  - [Chimpanzee model of hepatitis E virus infection].
AB  - For the study of the hepatitis E virus infection animal model, two chimpanzee
      were inoculated with hepatitis E virus. After one month of the inoculation, the
      animal got typical hepatitis profile. ALT, anti virus-IgM, antivirus-IgG, were
      detected in detail. The results showed solid HEV infection evidence of typical
      hepatitis within one month after the inoculation.

PMID- 12515161
TI  - [Cloning and sequencing of cDNA in NS3 region of Chinese hepatitis G virus
      isolated from Henan Province].
AB  - To study the genetic characteristics of non-structural region 3 of HGV in China,
      a HGV-RNA positive sample was collected from Henan. HGV RNA was extracted and
      amplified by RT-nested-PCR. We got four overlap fragments and they were cloned
      into plasmid vector pcDNA II. The cDNA was sequenced by the Sanger's method.
      Nucleotide homology between Henan strain and other reported HGV isolates
      (PNF2161, R10291, GBV-C) was 85.7% to 93.8% over the 2137 nucleotides examined.
      Comparison of amino acid sequence deduced from Henan strain with that of other
      isolates showed 96.1% to 97.7% homology. Three amino acid variations were found
      in NS3 region of all the three Chinese isolates of HGV. In addition, a N
      glycosylation site was found in the NS3 region of all the six isolates.

PMID- 12515162
TI  - [Preliminary clinic observation on the inhibition of HBV by receptor-targeted
      drug L-HSA-AraAMP].
AB  - To preliminarily observe the antiviral effect of receptor-targeted drug, the
      Lactosaminated Human Serum Albumin Arabinoside Adenine Monophosphate (L-HSA-Ara
      AMP), 10 patients with chronic type B hepatitis (HBsAg, HbeAg/HBV DNA positive)
      were treated with this drug for 5 days. The daily dose of L-HSA-Ara-AMP was 35
      mg/Kg (containing 1.5 mg Ara-AMP), whereas the usual daily dose of free Ara-AMP
      is 10 mg/Kg. In 10 patients treated, three patients' HBeAg became negative and
      six patients' HBeAg titer fell. Anti-HBc IgM all became negative in 4 anti-HBc
      IgM positive patients. In 8 HBV DNA positive patients, four patients' HBV DNA
      became negative and the other four patients' HBV DNA decreased. HBsAg remained
      positive in all of the ten patients. No adverse effects were observed. The
      results showed that L-HSA-Ara-AMP inhibits HBV as effective as free Ara-AMP, but
      at a daily dose 6.7 times lower than free Ara-AMP.

PMID- 12515163
TI  - [Genotypic analysis of hepatitis C viruses and its significance in interferon
      treatment].
AB  - To study the genotypes of HCV infection in Shanxi Province and the response of
      HCV genotypes to interferon therapy, the genotypes of HCV were analysed by
      restriction fragment length polymorphism in 94 chronic hepatitis C patients who
      were positive for HCV RNA (RT-PCR). It was shown that 80 patients (85.1%) were
      group I infection, 12 (12.8%) were group II infection and 2 (2.1%) were group
      I/II co-infection. 45 chronic hepatitis C patients with different genotypes (35
      with HCV group I, 10 with group II) received rIFN alpha-1b 3 MU three times a
      week for 6 months and were followed up to 12-34 months. The responsive rate was
      significantly higher in patients with group II infection (80%) than that in
      patients infected with group I (37.1%) (P < 0.05). Sustained response was
      observed in 60% for group II and in 17.1% for group I (P < 0.025). The date
      indicated that HCV group I is the major type of HCV infection in Shanxi Province
      the and HCV genotype seems to be an important factor in determining the response
      rate to IFN treatment in patients with chronic hepatitis C.

PMID- 12515164
TI  - [Studies on the basis of molecular biology of the phase change of influenza
      A(H3N2) viruses].
AB  - The analysis of nucleotide sequences on HA1 domain of 35 strains of influenza
      A(H3N2) virus showed that their HA1 genes all were 984 nucleotides in length
      coding for a HA1 protein with 328 amino acids and there was not any occurrence of
      insertion or deletion of nucleotides on HA1 genes among them. The appearance of
      "O" phase strain of influenza A (H3N2) virus was closely related with
      substitution at 226 position of amino acid on HA1 protein molecule and the three
      dimensional structural change of HA protein. The results in this paper indicated
      that the positions with multiple changes on HA1 protein molecule located at the
      top of HA protein, especially at antigenic determinant B site or receptor binding
      site. These further demonstrated that the substitution of amino acid on HA1
      protein molecule was caused mainly by suppress of herd immunity. This study also
      showed that the position of the cysteine and proline residues on the HA1 protein
      molecule were conservative and that the glycosylation sites located at N and C
      terminals, especially at N terminal of the HA1 protein The significance of such a
      distribute delta of glycosylation sites in the evolution of viral genes and
      epidemiology still remain unknown.

PMID- 12515165
TI  - [DNA cloning of Ad7 vaccine strain and sequence analysis of its Sma I H
      fragment].
AB  - Human adenoviruses have been a hot topic of study because of their potential
      utility for gene therapy and development of live viral vectored vaccines.
      Adenovirus types 4 and 7 have been given orally as vaccines for prevention of
      acute respiratory infections caused by these serotypes of adenovirus in U.S. army
      recruits for more than 30 years. Therefore, the advantage of using Ad4 and Ad7 as
      vectors in the development of oral live recombinant vaccine is obvious. For
      constructing Ad7 vector, 10.8-100 mu DNA of Ad7 vaccine strain has been cloned.
      The Sma I H fragment was sequenced using Ad7 DNA as a template and then the
      fragment was cloned by PCR. For verifying the sequence the fragment was sequenced
      again. The strategy we used to clone terminal end of adenovirus is reliable and
      practicable.

PMID- 12515166
TI  - [Expression of secreted ligand domain of vaccinia growth factor encoded by
      vaccinia virus strain tian tan in E. coli and insect cells].
AB  - Vaccinia virus growth factor (VGF) is encoded by an early gene of vaccinia virus
      strain TianTan located near the border between the terminal inverted repeats and
      the internal region of the viral genome as one copy. Its relationship to members
      of epidermal growth factor superfamily was discovered when computer searches of
      protein sequences revealed that VGF has strong sequence homology with these
      growth factors. To further get insight into the biological activity of VGF, we
      cloned and expressed the secreted ligand domain of VGF (VGFsl) encoded by
      vaccinia virus strain TianTan in E. coli and insect cells. The results of
      biological activity test indicated that expressed products is capable of binding
      to the EGF receptor, and stimulating EGF receptor tyrosin autophosphorylation to
      a level greater than that of EGF.

PMID- 12515167
TI  - [Construction of the prokaryotic expression plasmid pYNenv encoding the gp120 env
      gene of human immunodeficiency virus type 1 of yunnan strain].
AB  - The recombinant envelope protein of human immunodeficiency virus type 1(HIV-1) of
      Chinese Yunan epidemic strain was expressed in E. coli for confirming the
      antigenic domains of the protein. The recombinant prokaryotic expressive plasmid
      pYNenv was constructed by inserting the env DNA fragment which encode the gp120
      of HIV-1 Yunnan strain into pBV220. The env DNA fragment was obtained by nested
      polymerase chain reaction with the HIV-1 infected patients peripheral blood
      macrophage and monocyte genomes from Yunan HIV-1 epidemic area as template. The
      recombinant plasmid pYNenv was confirmed by restriction enzyme analysis. The
      recombinant protein was expressed in E. coli DH10b by pYNenv after vibration
      culture at 30 degrees C for 20 hours then at 42 degrees C for 5 hours and
      confirmed by SDS-PAGE electrophoresis. The protein can specifically react with
      the serum of HIV-1 infected patient from Yunan epidemic area by Western blot
      assay. The result showed that the recombinant protein can be used as antigen for
      detection of HIV-1 membrane glycoprotein antibody as well as for the further
      study of the role of envelope protein in pathology.

PMID- 12515168
TI  - [Construction and screening of type 1 human immunodeficiency virus specific phage
      antibodies combinatorial library].
AB  - Human monoclonal antibodies to type 1 immunodeficiency virus (HIV-1) gp120 were
      generated from phage antibody combinatorial library. METHODS: The human
      immunoglobulin heavy chain Fd and light chain k genes were amplified by half
      nested PCR from PBMC of patient infected with HIV. Phage antibody combinatorial
      library was constructed with the Fd and k chain genes using Pcomb3 as vector. The
      affinity selection and ELISA were adopted for generating specific phage
      antibodies. Partial DNA of a positive clone was sequenced and its soluble Fab was
      expressed in E coli. HIV-1 specific phage antibodies combinatorial library were
      constructed using the Fd and k genes and Pcomb3 vector. The library capacity was
      about 1.95 x 10(7). The specific phage antibodies were highly enriched after
      three rounds of biopanning selection against HIV-1 gp120 and 32% positive clones
      were detected by ELISA screening. DNA fragment coding for CH1 and CL derived from
      a positive clone was sequenced and its product was successfully expressed as
      soluble Fab which was specific for HIV-1 gp120. The HIV-1 specific phage antibody
      combinatorial library, and human monoclonal antibodies to HIV-1 gp120 have been
      used as tools for screening of neutralizing antibody to HIV-1, and the methods
      seem to be very crucial and applicable.

PMID- 12515169
TI  - [Generation of anti-rhEPO ScFv by using phage display technology].
AB  - In this paper, the recombinant phage antibody techniques was used to construct,
      clone, screen, and express anti-rhEPO single chain antibody ScFv. The variable
      region genes of antibody were amplified by PCR from a hybridoma cell line D3
      which secreted monoclonal antibody to rhEPO. The ScFv gene fragments were
      successfully cloned into phagemid vector pCANTAB5E. The recombinant phages were
      panned by rhEPO which was coated on a microtiter plate. After three rounds of
      panning, 8 clones were determined specifically binding to rhEPO antigen. The
      positive recombinant phagemids were extracted and transformed into non-suppressed
      E. coli HB2151. The soluble single chain antibody was expressed, and the
      specificity of the expressed ScFv was determined by ELISA. Western blot and Dot
      blot. The result of SDS-PAGE indicated that the apparent molecular weight of the
      target peptide which is mainly in culture supernatant is 32 kD. The DNA sequence
      data showed that the ScFv gene included 783 bp, encoding 261 amino acids.

PMID- 12515170
TI  - [A novel gene delivery system targeting to epidermal growth factor receptor
      overexpressing cancer cells].
AB  - A polypeptide with 33 amino acid residues was designed and synthesized. Its C
      terminal was composed of multiple lysine residues, which played as a DNA
      condensing agent, whereas the N terminal was the receptor binding domain of
      Epidermal Growth Factor(N32-K48). Through a spontaneous self-assembly process
      with electrostatic interaction, the synthetic peptide combined with a luciferase
      expression vector, pEBluc, to form an EGF receptor targeting nucleic acid
      complex. Significant luciferase activity was detected 48 hours after adding this
      complex directly to the culture medium of the A431 cells. This synthetic peptide
      could be used to construct a gene transfer system mediated by the endocytosis via
      EGF receptor. It promoted a very possibility of the gene therapy for the cancers
      such as glioma, melanoma and squamous carcinoma which are known of epidermal
      growth factor receptor overexpression.

PMID- 12515171
TI  - [Expression of human granulocyte-macrophage colony stimulating factor(hGM-CSF) by
      recombinant vaccinia virus and its effect on immunogenicity].
AB  - hGM-CSF was inserted into the down stream of P11K promoter of pJSB1175, which
      consists of HSV-1gD under the promoter P7.5K. The constructed plasmid
      pJSB1175D/GM-CSF was cotransfected with vaccinia virus Tiantan Strain into TK
      143. After selection and screening, recombinant virus RVJSB11D/GM-CSF was
      harvested. It was proved that the recombinant virus could express GM-CSF and HSV
      1gD at the same time by MTT assay and IFA in vitro. In vivo study showed that the
      expression of GM-CSF by RVJSB1175D/GM-CSF did not interfere with the HSV-1gD
      antibody production.

PMID- 12515172
TI  - [Study on relationship of the expression of platelet-derived growth factor and
      its receptor-beta in liver tissues with liver fibrosis].
AB  - The expression of platelet-derived growth factor(PDGF)-BB and PDGF receptor
      beta(PDGFR-beta) in liver tissues from viral hepatitis was detected by
      immunohistochemistry. The results showed that the expression of PDGF-BB and PDGFR
      beta in the liver tissues correlated closely with the degree of liver fibrosis.
      The levels of their expression in the liver cirrhosis and fibrosis stage S3-4 of
      chronic viral hepatitis(CH) were much higher than those in acute viral hepatitis
      and fibrosis stage S0-2 of CH. Meanwhile, the expression of PDGF and its receptor
      was associated with the expression of desmin-positive cells pro-collagen III
      peptide in liver tissues and tissue inhibitor of metalloprotenase-1 in serum. It
      is suggested that PDGF-BB and its receptor-beta may promote the progress of liver
      fibrosis by means of the activation, proliferation and differentiation of
      satellite cells.

PMID- 12515173
TI  - [The inhibitory effect of antisense--RNA of papillomavirus type 16 E6E7 genes on
      malignant phenotypes of cervical carcinoma cell line].
AB  - In our previous study, the malignant phenotypes of the NIH3T3 cells, transformed
      with HPV-16 E6E7 genes, could be inhibited by the antisense RNA of HPV-16 E6E7.
      In this study, the antisense RNA of HPV-16 E6E7 was induced into the cervical
      carcinoma cells, caski, which contained HPV-16 DNA. The results showed that the
      cellular growth velocity was down regulated by the antisense RNA of HPV-16 E6E7,
      the ability of forming cellular colonies in soft agar medium and the
      tumorigenicity in nude mice of CaSki cells were also inhibited by the antisense
      cellular colonies in soft agar median and the tumorigenicity in nude mice of
      Caski cells were also inhibited by the antisense RNA. In addition, the decrease
      of the expression of viral early genes in carcinoma cells was detected with
      Western blot assay. It denoted that the phenotypes and the carcinogenicity of
      tumor cells were inhibited by the associated antisense RNA, and this may be one
      of the pathways inducing tumor cells reversion.

PMID- 12515174
TI  - [Primary studies on the establishment of cytomegalovirus murine model].
AB  - Intraperitoneal inoculation of Murine cytomegalovirus(MCMV) into Balb/C mice at
      age of 4 weeks resulted in acute MCMV infection of the mice. The infected mice
      had body weight reduction, growth retardation, salivary gland swelling and death.
      A lethal dose was 5 x 10(6) PFU/ml of MCMV. Virus could be recovered from
      salivary gland and the infectivity titer of MCMV reached to a high titer of 2 x
      10(5) PFU/ml. Plaque formation of MCMV in 3T3/Swiss albino cells was identified.
      Histopathological examination showed the appearance of MCMV-specific
      intracytoplasmic inclusion bodies in neuron cells of the mouse brain.

PMID- 12515175
TI  - [Study on expression of transforming growth factor-beta 3 in the liver tissues].
AB  - 33 specimens of liver biopsy from patients with different types of viral
      hepatitis were detected for transforming growth factor-beta 3(TGF-beta 3) by
      immunohistochemistry. The results showed that TGF-beta 3 mainly distributed in
      the sinusal walls cells in sinus portal, areas fibrous, septum, hepatocytes in
      pseudolobes and necrotic areas of severe hepatitis. The expressing intensity of
      TGF-beta 3, was stronger in the cirrhosis, chronic severe hepatitis than that in
      the chronic and acute hepatitis. As the expression of TGF-beta 3 increased, the
      level of serum bilirubin ascended and plasmozyme activity was prolonged. It may
      be concluded that the expression of TGF-beta 3 is correlated with severe
      hepatitis and the progress of the liver cirrhosis.

PMID- 12515176
TI  - [Immunohistochemical study of Fas ligand in liver tissue of chronic hepatitis B
      virus infection].
AB  - To evaluate the role of apoptosis on liver injury of chronic hepatitis B, we
      studied the expression of Fas ligand and HBsAg immunohistochemically. Sixty-eight
      liver biopsy samples from patients with type B chronic liver disease were
      immunostained for Fas ligand and thirty-two of which were immunostained for
      HBsAg.35/68(51.47%) cases showed FasL immunoreactive in liver-infiltrating
      mononuclear cells, and more expression of FasL were found in cytoplasm of
      hepatocytes. Both were closely linked to the degree of inflammation in liver(P =
      0.008 and P = 0.011, respectively). But the expression of FasL had no close
      relationship with that of HBsAg in liver tissue (P > 0.05). These findings
      suggest that apoptosis caused by CTL through Fas-mediated pathway plays an
      important role in liver cell injury by hepatitis B virus infection. At the same
      time, FasL-positive hepatocytes may express cytotoxic activity and eliminate
      themselves by both fratricide and suicide; 'Bystander effect' can be used to
      account for the difference expression between FasL and HBsAg.

PMID- 12515177
TI  - [Relationship between T-lymphocyte subpopulation and soluble interleukin-2
      receptor (SIL-2R) in recurrent herpetic keratitis].
AB  - This article is to study the relationship between T-lymphocyte subpopulation and
      soluble interleukin-2 receptor (SIL-2R) in recurrent herpetic keratitis. We
      detected the T-lymphocyte subpopulation of peripheral blood and soluble
      interleukin-2 receptor(SIL-2R) in 30 cases of recurrent herpetic keratitis, 25
      cases of healthy people were set as contrast. The results showed that there were
      obvious decrease and of CD3, CD4/CD8, and magnificent elevation of soluble
      interleukin-2 receptor(SIL-2R) in sera of recurrent herpetic keratitis cases when
      compared with the contrasts, we hold that the lower immune function in recurrent
      herpetic keratitis cases may attribute to the high level of soluble interleukin-2
      receptor (SIL-2R) in the serum. The discovery can provide foundation for
      immunotherapy.

PMID- 12515178
TI  - [The transfection and morphological changes of human embryonic nasopharyngeal
      epithelia infected by Epstein-Barr virus cooperated with promoter in vitro and in
      vivo].
AB  - In order to detect the ability of EBV on transfecting and transforming human
      nasopharyngeal epithelia(HNE) isolated from human embryo, the HNE was cultured in
      vitro and then transplanted into nude mice. HNEs were treated by EBV, EBV + TPA
      and TPA in vitro, respectively. The mice transplanted with HNE tissues were
      injected subdermally by EBV, EBV + TPA and distilled water several times,
      respectively. The morphological changes indicated that EBV induced not only
      enhancement of foci and N/C ratio in cultured HNE which are important
      characteristics of malignant transformation, but also carcinogenesis of
      transplanted HNE, all of the carcinoma were EBV positive. TPA seems to increase
      EBV transfection rate (EBV PCR positive rate) in vitro, especially in the early
      stage. TPA alone did not exert effect on malignant transformation Cooperating
      with TPA, EBV induced early invasive carcinoma in vivo.

PMID- 12515179
TI  - [Early diagnosis of nasopharyngeal carcinoma using recombinant antigens expressed
      in bacteria].
AB  - An enzyme-linked immunosorbent assay(ELISA) was developed by using recombinant
      purified early antigens, EA-D and EA-R to detect IgA antibodies in sera from
      nasopharyngeal carcinoma(NPC) patients. 30 sera from NPC patients and 49 sera
      from normal persons were detected by the developed ELISA. The serum positive rate
      and antibody titer were compared with immunoenzymatic method(IE) on slide with
      Raji cells mears. ELISA is more sensitive and specific. The serum positive rate
      of NPC patients was increased from 70% by IE to 100% by ELISA and 77% of the
      serum antibody titer reached > or = 1:200. The results show that the expressed
      recombinant p138 and p54 antigens are effective for detection of EA/IgA antibody
      in sera from NPC patients and ELISA will be a sensitive, specific and convenient
      method for early diagnosis of NPC.

PMID- 12515180
TI  - [Detection of rotavirus RNA using DIG labelled probe prepared by polymerase chain
      reaction].
AB  - The digoxigenin (DIG) labelled cDNA probe of rotavirus was directly prepared by
      polymerase chain reaction (PCR). The results of cDNA-RNA hybridization showed
      that the DIG-cDNA probe exhibits rotavirus specificity and can detect as tiny as
      10 pg rotavirus RNA. 120 fecal samples of diarrhea from infants and young
      children were tested by dot-blot hybridization. It was shown that the positive
      rate of dot-blot hybridization(65.0%) was significantly higher than that of
      PAGE(49.1%). This study indicated that direct preparation of DIG-labelled
      rotavirus-cDNA probe by PCR is much faster and simpler than common method of
      labeling.

PMID- 12515181
TI  - [Sequence analysis of Ad7 vaccine strain 87 mu-97.4 mu fragment].
AB  - Adenovirus 7 vaccine strain(Ad7v) possesses potentiality to be used as a vector
      for producing recombinant vaccine. In order to construct Ad7 vector, the
      nucleotide sequence of a 3698 bp fragment(87 to 97.4 mu) of the virus DNA was
      analysed. The fragment encodes three ORFs namely, one ORF of early region 4(E4),
      one ORF of early region 3 and one ORF of fiber protein. The predicted amino acids
      of three ORFs(ORF 8.1 kD, 42.8 kD and 10.3 kD) share 33%, 43% and 44% homology
      with Ad2 E4 corresponding regions (ORF 3, ORF 4 and ORF 6/7) respectively. A
      comparison of the nucleotide and amino acid sequences of those fiber ORF
      demonstrated a higher homology between Ad7v and prototype strains of Ad7v than
      those between Ad7v and Ad7h. The Ad7v E3 15.4 kD protein shares 86%, 88%, 90% and
      98.5% amino acid homology with the equivalent region of ad7h E3 15.3 kD protein,
      Ad4 E3 region 15 kD protein, Ad3 E3 15.3 kD and Ad7p E3 15.3 kD protein protein
      respectively, but only 68% with Ad2 E3 14.7 kD protein.

PMID- 12515182
TI  - [Genome shift of hepatitis E virus in Asia].
AB  - Dideoxy chain termination method was applied to sequence hepatitis E virus
      structure gene of Asia isolates, cDNA sequence and amino acid residues were
      determined. The results showed that among Asia countries: Indian, Burma, China,
      Pakistan and Kirghiz Republic, Hepatitis E virus genome shifted within the range
      of 5% and amino acid residues shifted within 1% compared with Mexico isolate.
      Asia Hepatitis E virus isolates have limited genome shift, which suggests
      recombinant Hepatitis E vaccine based on Asia HEV gene might protect all HEV
      infection in this area.

PMID- 12515183
TI  - [Synthesis and preliminary study on cleavage activity of ribozyme to hepatitis B
      virus preS2 gene in vitro].
AB  - In this paper, a multi-target hammerhead ribozyme gene was synthesized directed
      against 110, 122 and 132 sites of nucleotide of HBV preS2 gene. The target gene
      fragment was cut from HBV genome containing plasmid pCP10. Both of the ribozyme
      and the target gene fragments were cloned into pGEM3Zf(-) plasmid and sequenced
      by dideoxy chain termination method. The transcription of both gene fragments was
      performed in vitro utilizing T7 RNA promoter in pGEM3Zf (-) plasmid. The cleavage
      activity of ribozyme to substrate was confirmed in vitro. For further evaluating
      intracellular function of ribozyme, two ribozyme-retroviral recombinant plasmids
      with different promoter type pDOR-ripe and tRNA-ripe were constructed. Pseudo
      virus was collected through routine packaging procedure and transduted into
      2.2.15 cells. RIA data showed a stable inhibition of pHSA-R antigen expression to
      the lowest extent of 41.01% +/- 4.16 and the highest extent of 51.45% +/- 4.57
      within 4 weeks after transduction. No influence, however, on HBsAg and HBeAg
      expression was demonstrated after ribozyme gene transfer.

PMID- 12515184
TI  - [Detection of TT virus infection and clinical investigation in patients with
      liver diseases].
AB  - 104 serum samples from patients with liver diseases were detected for TTV DNA by
      nested-PCR method. The results showed that 25 of 104(24%) were positive for TTV
      DNA. Among 104 samples, 48%(12/42) were positive for nonA-E and G 19% (4/12) were
      positive for hepatitis A 25% (8/32) were positive hepatitis B 11.1% (1/9) was
      positive hepatitis C 4 of 6(66.7%) fulminant hepatitis cases were detected
      positive for TTV DNA. The partial gene of two TTV isolates from the patients were
      cloned and sequenced. The sequence analysis shows that there is 98.4% nucleotide
      identity between AB008394(from Japan) and one isolate from the patient
      (TTVEC023). The results suggest that TTV is associated with acute, chronic and
      fulminant hepatitis. TTV infection would be the important cause of non A-E and G
      hepatitis.

PMID- 12515185
TI  - [Evaluation on the anti-hepatitis C virus enzyme-linked immunosorbent diagnostic
      kits].
AB  - Ten different anti-HCV ELISA kits, four manufactured from abroad (ABBOTT,
      Innogenetics, Murex, Monolisa) and six in China, were evaluated by China national
      anti-HCV panel(100 positive, 98 negative) and Boston Biomedical Inc. (BBI) anti
      HCV mixted titer performance panel(23 positive and 2 negative). The detective
      rates in 100 China national anti-HCV positive panel were 98% by ABBOTT EIA 2.0,
      96% by BHY, SKH and XWK, 95% by BBS and HHM, 97% by SCJ, and that in 23 BBI anti
      HCV positive panel were 100% by ABBOTT EIA2.0, but 91% by Murex, 87% by
      Innogenetics and Monolisa, 74% by BHY, 87% by SKH, 83% by XWK and HHM, 70% by
      BBS, 91% by SCJ. The specificity for all negative panels were similar in all
      kits. According to the results of HCV RIBA test (Ortho HCV RIBA 2.0), the
      structural antigens contained in all kits were almost the same, but the
      antigenicity of HCV nonstructural proteins were different, in the kits made in
      China they were lower than that made from abroad.

PMID- 12515186
TI  - [The effect of ribozyme RzDS on duck hepatitis B virus].
AB  - To study the effect of ribozyme in vivo, the hammerhead ribozyme RzDS was
      designed and synthesized, which aims at the pregenome RNA of DHBV(LJ-76) at the
      736 site of the genome. The RzDS cleaved efficiently its substrate in vitro. We
      constructed pJ-RzDS, in which RzDS was inserted into pJ120 plasmid under the
      control of PII promoter. After homogenous recombination with the vaccinia virus,
      Tian Tan strain, we got the recombinant(V-RzDS) which carried RzDS. V-RzDS was
      injected into nestling Beijing ducks preinfected with DHBV. On the tenth day
      after intravenous injection, DHBV DNA and DHBsAg in serum were detected. The
      quantity of DHBV DNA and DHBsAg were evidently lower than that of the controls,
      when V-RzDS injection was simultaneously given with DHBV. It suggests that RzDS
      can block replication and expression of DHBV in vivo.

PMID- 12515187
TI  - [Study on expression of P16 protein in the liver tissue of viral hepatitis].
AB  - P16 protein is a cell cycle regulator involved in the genesis of many types of
      tumors. In order to study the significance and expression of P16 protein in liver
      tissue of viral hepatitis, 48 patients with viral hepatitis and 7 cases with
      hepatocarcinoma were investigated by immunohistochemistry. The results showed
      that the positive rate of P16 protein expressed in the liver tissues of mild
      (85.0%) and moderate (91.66%) chronic viral hepatitis were significantly higher
      than that in liver cirrhosis and hepatocarcinoma (P < 0.01, 0.001), this suggest
      that the expression of P16 plays an important role in the carcinogenesis.

PMID- 12515188
TI  - [An observation on antiviral effect of IFN--alpha N1 (Wellferon) in patients with
      chronic hepatitis B].
AB  - In order to observe the antiviral effect of IFN-alpha N1(Wellferon, British
      Glaxowellcome Company) on CHB, each 50 cases of CHB were selected as the therapy
      group and the control group. The patients in the therapy group were administrated
      with 3MU of IFN-alpha N1 once a day for one week, and then 3MU of IFN-alpha N1
      three times weekly for 11-23 weeks, whereas the patients in the control group did
      not receive any antiviral treatment. At 3 months, the serum alanine
      transaminsae(ALT) was decreased to normal level in 84%(42/50) cases of the
      therapy group, while only in 46% (23/50) cases of the control group (P < 0.01).
      The negative seroconversion rate of HBeAg was 56.7% (17/30) and 10.8% (4/37), of
      HBV DNA was 36.4%(12/33) and 5.9% (1/17) in therapy and control groups
      respectively. There was obvious difference in two groups. The results suggest
      that IFN-alpha N1 is satisfying antiviral drug for CHB patients or patients non
      responsive to other IFNs.

PMID- 12515189
TI  - [Detection of serum hepatitis B virus DNA in patients with various chronic liver
      diseases].
AB  - With established competitive polymerase chain reaction (PCR) method, serum HBV
      DNA concentration was determined in 125 patients with primary hepatic carcinoma(n
      = 38), liver cirrhosis (n = 36) and chronic hepatitis (n = 51) with different
      serum HBV immunological markers. The results showed that: (1) No significant
      variation of HBV DNA concentration was detected in patients with different
      chronic liver diseases; (2) About one third of the examined patients whose five
      serum HBV markers were negative and anti-HBs were positive showed low level of
      viral replications; (3) The total concentration of HBV DNA in the patients with
      positive HBeAg were significantly higher than that in patients positive for anti
      HBe, but also found a high HBV DNA concentration in some of the latter. It
      suggests that the manner of viral replication were not correlated with the period
      of the chronic liver disease. So HBV replicative status may not be completely
      determined only by seroconvertion of HBeAg to anti-HBe.

PMID- 12515190
TI  - [Low frequency of precore stop mutation in patients with dual infection of
      hepatitis B and C viruses].
AB  - In order to study the mutation of hepatitis B virus(HBV) precore gene in patients
      with dual infections of HBV and HCV and its possible clinical significance, the
      precore stop codon mutation (stop 28) was analysed by polymerase chain reaction
      (PCR) and restriction fragment length polymorphism(RFLP) in patients with chronic
      liver disease, which were 25 cases with HBV DNA and HCV RNA positive(group A) and
      31 cases with HBsAg and HBV DNA positive but anti-HCV and HCV RNA negative (group
      B). The results showed that the serum HBV DNA positive rate by 1st PCR in
      patients with dual infections(group A, 16%) was significantly lower than that in
      patients with HBV infection alone (group B, 65%), the stop 28 positive rate was
      also significantly lower (28%, versus 68%). The results suggest that the low
      frequency of precore stop codon mutant in patients with HBV and HCV dual
      infections was possibly due to low replication of HBV.

PMID- 12515191
TI  - [High-level expression of human immunodeficiency virus type 1 gp120 protein in E.
      coli].
AB  - In order to improve protein expression and to produce good and cheap diagnostic
      antigen, the gene fragment (560bp) in N-terminal of gp120 of HIV-1 LAV strain was
      amplified by PCR. After digested by EcoR I and Sal I, the fragment was cloned
      into a high-level expression vector pET28a. The recombinant plasmid pET/120
      transfecting BL21 (DE3) produced the protein with high-level expression in the
      host cell BL21(DE3), which was further proved having good antigenicity and high
      specificity by indirect ELISA and Western-blot assay. The protein expressed was
      about 50% of the total bacterial protein by SDS-PAGE electrophoresis test. It was
      highly expressed in the prokaryotic expression system.

PMID- 12515192
TI  - [The study on purification and characterization of HIV-1 reverse transcriptase
      from a recombinant strain of E. coli].
AB  - Of the HIV proteins, reverse transcriptase(RT) has been probably the most useful
      target protein for screening and designing of its specific inhibitors. Because
      retroviral replication is absolutely dependent on both the RNase H and the
      polymerase function of RT and, so far as is now known, RT does not play a direct
      role in the life cycle of a normal cell. Under suitable fermentation conditions
      in our experiments, HIV-1 RT was highly expressed in E. coli JM109(pKRT-2)* by
      inducing the trc promoter with isopropyl-beta-Dthiogalactopyranoside(IPTG). 1. 1
      mg of purified RT was obtained from one liter culture of bacteria by DEAE
      cellulose and phosphaellulose chromatography. SDS-PAGE analysis of the purified
      RT showed two major protein bands of 66 kD and 51 kD, indicating that the
      purified RT was a heterodimer composed of two subunits. Results of enzyme assay
      showed that the purified RT had high activity(1.4 x 10(4) umit/mg). We also
      improved the reaction system of enzyme assay. The effect of PFA on HIV-1 RT was
      determined with the improved enzyme assay and the mechanism of inhibition was non
      competitive with respect to substrate consistent with the reports of Dr. Bo
      Oberg. This suggests that the purified HIV-1 RT by this simple method can be
      applied to the anti HIV-1-drug screening. (*E. coli JM109(pKRT2) was obtained
      from NIAID, NIH; pKRT2 from Dr. Richard D'Aquila and Dr. William C. Summers.)

PMID- 12515193
TI  - [The purification and application of Epstein-Barr virus gp125].
AB  - Epstein-Barr virus (EBV) virion capsid antigen (VCA) gp125 as a diagnostic
      antigen was expressed in infected cells by recombinant vaccinia virus. The
      presence of IgA antibody to VCA of EBV was tested by ELISA in sera from
      nasopharyngeal carcinoma (NPC) patients and normal individuals. The ELISA
      consisted of three steps involving test serum, mouse monoclonal antibody to human
      IgA and rabbit anti-mouse IgG. The antibody titers of sera determined by this way
      correlated well with those by IF. The GMT by ELISA was 12 times higher than that
      by IF. Furthermore, efforts to develop gold-conjugated immunosorbent assay
      (GCISA), which is a more sensitive assay for measuring IgA antibody to VCA, has
      met with initial results.

PMID- 12515194
TI  - [The construction of a general adeno-associated virus vector].
AB  - The general adeno-associated virus(AAV) vector pACR-Neo was constructed by
      substituting AAV's construct gene with cassette that was composed of CMV-IE
      promoter, multiple cloning sites and SV40-polyA. After transfecting pACR-Neo into
      recombinant AAV's packaging cell line AE1201, which was infected by Adenovirus 5
      before transfection, we got rAAV/ACR-Neo at the titer of 4.2 x 10(5) CFU/ml.
      Using rAAV/ACR-Neo infected host cell A549, the recombinant AAV could transfer
      reporter gene Neo into host cell and mediate the integration of viral genome into
      host cell's chromosome DNA. By extracting chromosome DNA of host cell A549 that
      had been infected by rAAV/ACR-Neo, and digestion respectively with restriction
      endonuclease PvuII and HindIII, each of which has only one cutting site within
      rAAV/ACR-Neo's genome. We did Southern blot to check the hybridization of
      endonuclease digested chromosome to digoxin labelled Neo gene probe. After
      analyzing the experimental results, we found that rAAV/ACR-Neo's genome had
      integrate into host cell's chromosome compared to wild type AAV's site-specific
      integration. Through this work, we constructed a general AAV vector successfully.
      It lays foundation for research on AAV vector and application on gene therapy.

PMID- 12515195
TI  - [Human herpesvirus-6 infection induces IL-10 production in monocytes].
AB  - In this report, interleukin 10(IL-10) and other cytokines were evaluated through
      reverse transcription-polymerase chain reaction (RT-PCR) and sandwich ELISA to
      explore possible immune pathogenesis of human herpesvirus 6 (HHV-6) infection.
      The results showed that IL-10 was expressed in HHV-6 infected monocytes. Kinetic
      studies found that transcription of IL-1 beta, IL-6 and TNF-alpha mRNA decreased
      with accumulation of IL-10 mRNA. When endogenous IL-10 induced by HHV-6 was
      blocked using anti-human IL-10 monoclonal antibody, the production and the
      expression of TNF-alpha, IL-1 beta and IL-6 markedly increased as compared with
      infection by HHV-6 alone, indicating that endogenous IL-10 inhibited cytokine
      production at the transcription level in HHV-6 infected monocytes. IL-10 has been
      shown to suppress Th1 response and down-regulate monocyte/macrophage function.
      The data from our studies suggest that disturbance of immune function and latent
      infection resulting from HHV-6 infection might partially contribute to endogenous
      IL-10 production.

PMID- 12515196
TI  - [The relationship between herpes simplex virus II, human papillomavirus infection
      and infertility after artificial abortion].
AB  - In order to study the relationship between infection of sexually transmitted
      virus Herpes simplex virus II (HSV2), Human papillomavirus (HPV) and female
      infertility after artificial abortion, we collected 60 genital samples from
      infertile women who had accepted artificial abortions and 39 genital samples from
      normal women. Polymerase chain reaction (PCR) was used to detect HSV2 and HPV.
      The results were compared by x2. The positive rate of HSV2 in infertile and
      normal women were 80.0% and 25.6% respectively, there was a significant
      difference (P < 0.01); but that of HPV were 53.5% and 33.3%, which slowed no
      significant difference (P > 0.05). Mixed infection rates of HSV2 and HPV were
      43.3% and 23.1% in infertile and normal women, a significant difference (P <
      0.05) was statistically calculated. The results showed that there was a
      relationship between infertility after artificial abortion and genital infection
      of HSV2 and HPV or mited infection of HSV 2 and HPV. Taking total 99 genital
      samples into calculation, the mired infection rate of HSV 2 was 35.35%, a
      significant relatedness of HSV2 and HPV infection to infertility was proved by
      chi 2, chi 2 = 12.5, P < 0.01.

PMID- 12515197
TI  - [The study on detection of human parvovirus B19 DNA in spontaneous abortion
      tissues].
AB  - 116 spontaneous abortion tissues were detected for human parvovirus B19 (HPV B19)
      DNA by nested polymerase chain reaction. Of the abortion tissues detected, 66
      were paraffin embedded and 50 were fresh abortion tissues, At the same time, 25
      abortion tissues from healthy artificial abortion women were collected as
      control. The results showed that 27.3% (34/116) of 116 spontaneous abortion
      tissues were positive for HPV B19 DNA, and only 4% (1/25) were positive in the
      control group, the discrepancy was significant chi 2 = 5.769(P < 0.05). It
      suggests that there is a relationship between spontaneous abortion and HPV B19
      infection. HPV B19 infection may be an important factor in spontaneous abortion.

PMID- 12515198
TI  - [The study on in vivo erythropoietin gene transfer for treatment of renal anemia
      in animal model].
AB  - To explore the possibility of gene therapy to renal anemia, the receptor mediated
      erythropoietin (EPO) gene transfer in vivo had been tested. EPO gene was inserted
      to an EBV replicon expression vector to form the plasmid pEPO, Renal anemia rat
      had been induced by feeding with adenine, and 450 micrograms of the pEPO was
      delivered by perfusion into the rat peripheral circulation in the form of soluble
      DNA/galactosylate histone complex. 13 days after injection, the number of
      peripheral red cells was counted and the concentration of hemoglobin was
      measured. The results demonstrated that symptom of anemia had been significantly
      improved(P < 0.01), when compared with that of the control test. (the red cell
      number was 492 vs 409, and the hemoglobin was 11.4 vs 9.1).

PMID- 12515199
TI  - [An etiological and serological study on Dengue epidemic in Guangdong Province].
AB  - In 1978-1995, Dengue fever epidemics(serotype 1-4) occurred in Guangdong
      Province. Among 9 species of mosquitoes found in the epidemic areas, the positive
      rate of virus isolation in Aedes albopictus was 20.69%, in Aedes aegypti 18.95%,
      in Culex quinquefasciatus 10.29%, Dengue viruses were not isolated in other 6
      species of mosquitoes. The positive rate of virus isolation in the three species
      showed no significant differences (chi 2 = 2.77 P > 0.05). Aedes aegypti was the
      main transmitting vector in Hainan Island and Zhanjiang District, whereas Aedes
      albopictus was in the other epidemic areas. The positive rate of virus isolation
      within 3 days of disease onset was between 73.58% and 82.05%, but the virus could
      still be isolated on the 8th day of disease onset. The highest antibody positive
      rate from the patients' paired-sera was 93.89% and the lowest was 33.71%. IgM
      antibody could be detected 5 days after the disease onset in some cases, even on
      the 33rd day of disease onset. These results suggest that virus isolation by
      collecting patient's blood within 1-4 days of disease onset, or IgM antibody
      detection after 5 days of disease onset can be used as method for early and rapid
      diagnosis of the disease.

PMID- 12515200
TI  - [Cloning, sequencing and expression of hepatitis E virus structural gene in E.
      coli and application of the recombinant products for diagnosis].
AB  - The prokaryotic expression vector PEGX-3X was used to express hepatitis E virus
      (HEV) open reading frame 2(ORF2 402-660). The recombinant protein was soluble in
      PBS buffer and was purified by the glutathione Sepharose 4B affinity column. When
      the purified recombinant protein was applied to detect HEV antibodies in sera of
      clinical patients, the results were quite consistent with the HEV diagnostic kit
      from Diagnostic Biotechnology Ltd(DBL), Singapore. The recombinant protein was
      more reactive with HEV antibodies than DBL reagent.

PMID- 12515201
TI  - [Detection of hepatitis G virus infection among clinical patients with
      hepatitis/liver diseases in China by reverse transcription-nested polymerase
      chain reaction].
AB  - According to two highly conserved genome sequences within the helicase(NS3)
      region and 5'-uncoding(5' UTR) region, we designed two sets of primer pairs to
      detect HGV RNA by RT-nested PCR in order to study HGV infection in Chinese
      population. Three hundred and fifty-four serum specimens of various liver
      diseases were collected from Beijing, Qin Huangdao and Henan areas. Seventy-nine
      out of 354(22.3%) specimens were HGV RNA positive. Among 254 known clinical
      hepatitis/liver disease samples, 50(19.6%) were HGV RNA positive. Thirteen HGV
      RNA positive samples(30.2%) were derived from 43 cryptogenic or nonA-E hepatitis.
      In 57 commercial blood donors who were antibody positive to HCV 16(30.2%) were
      HGV RNA positive, suggesting HGV infection is common in various population. It
      may be an etiological factor which leads to nonA-E hepatitis and post-transfusion
      hepatitis.

PMID- 12515202
TI  - [Identification of hepatitis C or/and G virus RNA in one tube by reverse
      transcription nested polymerase chain reaction].
AB  - Hepatitis C and G viruses belong to the flaviviridae family. They have similar
      modes of transmission. The dual infection of HGV and HCV were reported. A
      simultaneous detection for HCV or/and HGV was established by reverse
      transcription nested polymerase chain reaction(RT-nested PCR). The primers were
      derived from the 5' non-coding region of HCV and NS3 region of HGV, and the
      length of the PCR product was between 170 bp and 300 bp. RT-nested PCR can be
      finished in one test tube and HGV and/or HCV can be detected simultaneously in
      one RT-nest PCR. 153 samples were detected by his method. Our results showed that
      the established assay is useful for screening and identification of HCV or/and
      HGV RNA. This method is simple and specific practicable.

PMID- 12515203
TI  - [Effect of varied sample treatment procedures on detection of hepatitis B virus
      DNA].
AB  - The detective sensitivity vary obviously in the assay of HBV DNA by means of
      polymerase chain reaction with 18 different sample treatment procedures. Higher
      sensitivity was found in three methods, namely, guanidine
      thiocyanate/phenol/chloroform, NaoH denaturation and sodium octanoate. The
      procedure of phenol/chloroform was too labor-intensive to be accepted in routine
      clinical testing, sodium octanoate which may suppress the inhibitory effect of
      denatured albumin on the polymerase chain reaction and thus the sensitivity was
      higher than the method of NaOH denaturation. Treatment of samples with 30-50
      mmol/L of sodium octanoate in final concentration for the detection of HBV DNA
      has shown to be very sensitive, simple and reproducible.

PMID- 12515204
TI  - [A review of the research on malignant hemopathies treated with arsenium
      containing Chinese drugs].

PMID- 12515205
TI  - [Species and distribution of medicinal plant Hypericum in Guizhou].
AB  - OBJECTIVE: To gain a clear idea on the resources of medicinal plant Hypericum in
      Guizhou. METHOD: Conducting field investigation and consulting related specimens
      and data. RESULT: The distribution, growing environment and medicinal parts of 18
      species of Hypericun have been clarified, and a key for their identification is
      given. CONCLUSION: A scientific basis for further study of the medicinal plant
      Hypericum in Guizhou Province has been provided.

PMID- 12515206
TI  - [A survey on botanical origins of drug Xue Lianhua produced in China].
AB  - OBJECTIVE: Based on an to investigation and identification of commercial samples
      to find out the original species and resources of Xue Lianhua. METHOD: Botanical
      and macroscopical identification. RESULT: The main original species of the plant
      are Saussurea involucrata, S. medusa, S. gossypiphora, S. polylada, S. laniceps,
      S. tridactyla, S. gnaphaloides, S. kingii, S. obvallata, S. tangutica, S.
      globosa, S. longifolia, Soroseris erysimoides, So. glomerata and So. umbrella.
      CONCLUSION: The flower and stem of S. involucrata and S. polylada and the whole
      herb of S. medusa and S. gossypiphora are used as Xue Lianhua in most areas of
      China.

PMID- 12515207
TI  - [A study on bark quality of Magnolia officinalis Rehd. et Wils].
AB  - OBJECTIVE: To understand the main factors influencing the bark quality of
      Magnolia officinalis so as to theoretically establish a basis for quality
      assessment, genetic improvement and layout of bark producing areas. METHOD:
      Eighty-two samples from the main bark producing areas(11 counties of 7 provinces
      such as Zhejiang, Fujian, Sichuan, Hunan, Guangxi, Jiangxi and Hubei) were
      collected. Totally there were 121 samples, including 39 from the trial stand
      located in Jingning of Zhejiang the obtained out of the seeds from the bark
      producing areas mentioned above. HPLC was used in the analysis of phenols
      contained in the bark of Magnolia officinalis. RESULT: The main factors
      influencing the bark quality have been made clear. CONCLUSION: The quality is
      affected by provenance, leaf shape, DBH, tree height, crown size, age, bark
      thickness color of bark powder, oiliness, grounding nature, bark type, position
      of sampling, etc., of which provenance, leaf shape, powder color, bark thickness
      and DBH are the most influential factors. These factors should be fully
      considered when making quality assessment and genetic improvement of the bark of
      Magnolia officinalis.

PMID- 12515208
TI  - [Effect of processing contents of saccharides in Danggui].
AB  - OBJECTIVE: To explore the effect of processing on the contents of saccharides in
      Danggui. METHOD: The contents of reducing saccharides, water-soluble saccharides
      and poly saccharides in Danggui and its processed products were determined by
      phenol-H2SO4 method. RESULTS: The contents of saccharides in the alcohol-broiled
      product were higher than those in the crude drug. CONCLUSION: Different
      processing methods have significant effects on the above saccharides, which
      administers to the interpreparation of the theory of Danggui processing.

PMID- 12515209
TI  - [A new fatty ketone of Radix Polygoni Multiflori Preparata].
AB  - OBJECTIVE: Investigating the chemical constituents of Radix Polygoni Multiflori
      Preparata. METHODS: Compounds were isolated from the CHCl3 extract with column
      chromatography on silica gel, and identified on the basis of spectral
      analysis(IR, EI-MS, 1H-NMR, 13C-NMR) and phytochemical properties. RESULTS: Two
      compounds were isolated and identified as 1,2-dihydroxynonadecone-3(I) and gallic
      acid(II). CONCLUSION: Compound I is a new compound.

PMID- 12515210
TI  - [Extraction and isolation of active component for inhibiting PC3 cell
      proliferation in vitro from the fruit of Lycium barbarum L].
AB  - OBJECTIVE: To extract and isolate the active component inhibiting PC3 cell
      proliferation in vitro from the fruit of Lycium barbarum. METHOD: The active
      components of the fruit of L. barbarum were extracted by water, 95% ethanol, 50%
      ethanol respectively. Then, ethanol extract was extracted with acetone and n
      butanol and isolated by SiO2 column and purified by TLC to obtain the active
      component. The chemical structure of active component was identified by the
      spectral analysis. MTT assay was used to compare the inhibition activity(IC50) of
      PC3 cells proliferation of the all extracts. RESULT: According IC50, the most
      active component among all extracts isolated from the fruit of L. barbarum
      isscopoletin. CONCLUSION: Scopoletin is the active component of the fruit of L.
      barbarum for inhibiting PC3 cell proliferation.

PMID- 12515211
TI  - [Studies on constituents in Uncaria macrophylla Wall].
AB  - OBJECTIVE: To study the chemical constituents of Uncaria macrophylla. METHOD:
      Compounds were isolated by Columu Chromatography, and the structures were
      identified by NMR spectral data and other methods. RESULT AND CONCLUSION: Six
      compounds were isolated and identified as ursolic acid, 3 beta-6 beta-23
      trihydroxyurs-12-en-28-oic acid, 3 beta, 6 beta, 19 alpha-trihydroxyurs-12-en-28
      oic acid, epicatechin, beta-sitosterol and daucosterin. All the compounds were
      isolated for the first time from the plant.

PMID- 12515212
TI  - [Studies on alkaloids of Asteropyrum cavaleriei (Levl. et Vant.) Drumm. et
      Hutch].
AB  - OBJECTIVE: To investigate the chemical constituents in the plant of Asteropyrum
      cavaleriei. METHOD: The Chemical constituents were extracted with cation exchange
      resin 732 and separated by column chromatography, and the structures were
      identified by spectral analysis. RESULT: Four compounds were isolated and
      identified as berberine, berberrabine, palmatine and magnoflorine. CONCLUSION:
      All compounds were separated from A. Cavaleriei for the first time.

PMID- 12515213
TI  - [Studies on method for the determination of kaerophyllin in Bupleurum smithii
      wolff Wolff var. parvifolium].
AB  - OBJECTIVE: To establish a quantitative method for the determination of
      kaerophyllin in Chinese medicine Bupleurum smithii ver. parvifolium. METHOD:
      Kaerophyllin was determined by HPLC, the mobile phase consisted of methanol
      water(70:30), the flow rate was 1 ml.min-1, the eluate was monitored with UV
      detector at 328 nm. RESULT: The average recovery was 97.1% with RSD = 2.15 (n =
      5). CONCLUSION: The result was precise and stable. This method was sensitive and
      its repeatability was excellent. This method may serve determination of
      kaerophyllin in B. smithii var. parvifolium.

PMID- 12515214
TI  - [Effect of haidonghua powder(HDHP) on hypothalamic obesity in rats].
AB  - OBJECTIVE: To study the effect of HDHP including Laminaria japonica Aresch. and
      Benincasa hispida(Thunb.) Cogn. etc. on antiobesity in rats with hypothalamic
      obesity. METHOD: A rat model of hypothalamic obesity induced by MSG was used and
      the relative indexes was observed. RESULT: HDHP(2.5 g.kg-1) could significantly
      reduce the Lee's index as well as the size of fat cells. HDHP did not influence
      the serum levels of T3 and T4, insulin and aldosterone, did not inhibited
      appetite not led to diarrhea. CONCLUSION: HDHP has the effect of anti-obesity,
      Without any influencing on the function of thyroid gland and metabolism of water
      and salt. The mechanism is related to the reduction of fat cell size and the
      accumulation of fat.

PMID- 12515215
TI  - [Mechanism of anti-inflammatory action of Huanglian Jiedu decoction a traditional
      Chinese prescription].
AB  - OBJECTIVE: To elucidate the mechanism of anti-inflammatory action of Huanglian
      Jiedu Decoction (HJD). METHODS: An acute inflammatory air-pouch was established
      in mice by s.c. injecting air and 1% carrageenan. A mouse endotoxeamia induced by
      lipopolysaccharide was also used. Splenocyte proliferation was quantified with 3
      (4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetery.
      NO2- concentration was examined by a Griess reagent and interleukin-1 activity
      was evaluated in thymocyte proliferation. RESULTS: HJD significantly inhibited
      the leukocyte infiltration and PGE2 production in the mouse air-pouch model. In
      the in vitro assay, HJD significantly inhibited concanavalin A(Con A)-induced
      transformation of spleen cells isolated from the endotoxeamia mice, but did not
      influence that from the normal mice. HJD did not affact Con A-induced interleukin
      2 production in splenocytes in either normal or endotoxeamia mice. HJD remarkably
      reduced interleukin-1 and NO production in peritoneal macrophages elicited by
      lipopol ysaccharide. CONCLUSION: HJD displays an anti-inflammatory effect mainly
      through inhibiting the production of inflammatory cytokines including IL-1, NO
      and PGE2.

PMID- 12515216
TI  - [Effects of tetrahydroberberine on peripheral vascular dopamine DA1 and DA2
      receptor subtypes].
AB  - OBJECTIVE: To study the effect of tetrahydroberberine (THB) on the peripheral
      vascular dopamine DA1 and DA2 receptors. METHOD: Using isolated vascular rings
      method. RESULT: THB(0.1-10 mumol.L-1) shifted the dose-response curves to the
      right in a nonparallel fashion and decreased the maximal response (Emax) of both
      the fenoldopam(FODA, a selective DA1 agonist)-induced and the propyl-butyl
      dopamine(PBDA, a selective DA2 agonist)-induced vasorelaxation, showing a non
      competitive antagonistic action. The pD'2 values of THB for FODA in the renal,
      pulmonary and mesenteric arteries were 5.29, 5.37 and 5.46, respectively, while
      for PBDA in the mesenteric and femoral arteries were 5.53 and 5.48, respectively.
      The potencies of this antagonistic action were weaker than those of SCH23390, a
      selective DA1 antagonist, domperidone, a selective DA2 antagonist and l-SPD, a
      mixed DA1/DA2 antagonist, domperidone, a selective DA2 antagonist and l-SPD, a
      mixed DA1/DA2 antagonist. CONCLUSION: THB is a mixed peripheral DA, and DA2
      receptor antagonist similar to l-SPD.

PMID- 12515217
TI  - [Main achievements, problems and measures in the study on the chemistry and
      pharmacology of Chinese herbal drugs during the past 50 years since the
      foundation of the People's Republic of China].

PMID- 12515218
TI  - [An preliminary comparative study on physiological activity of Fritillaria
      pallidiflora Schrek. and F. delavayi Franch].
AB  - OBJECTIVE: To compare the physiological activity of Fritillaria pallidiflora
      alkaloids(FPA) with that of F. delavayi alkaloids(FDA). METHOD: Xylene-induced
      ear swelling in mice, SO2-induced cough in mice, expectorant experiment on
      phenolsulfon phthalein excretion and bacteria incubation in vitro, etc. RESULT:
      The total alkaloids of both FPA and FDA(i.g., 400 mg.kg-1 and 200 mg.kg-1) have
      anti-inflammatory, antibechic and expectorant effects, but the former is more
      effective than the latter. Given the same dosage, FPA is still more effective
      than FDA. FPA can inhibit Hemophilus influenzae, Staphylococcus aureus and
      Streptococcus pneumoniae, etc, more effectively than FDA. CONCLUSION: In anti
      inflammatory, antibechic, expectorant and bacteriostatic effects FPA is superior
      to FDA.

PMID- 12515219
TI  - [A study on pollen morphology of Dipsacus].
AB  - OBJECTIVE: To study the pollen morphology of Dipsacus L. produced in China.
      METHOD: Examining the pollen morphology of 17 species and 2 varieties of Dipsacus
      L. with light microscope and scanning electron microscope. RESULT: The shape of
      pollen grains is spheroidal and the aperture is tricolpate. The ornamentation of
      exine may be divided into 3 types: dispinulate-reticulate, dispinulate-foveolate,
      dispinulate-rugulate or nearly smooth. CONCLUSION: Dipsacus is a natural class
      group, and the slight difference of its pollen grains is useful to some extent in
      the division of species.

PMID- 12515220
TI  - [Determination of organochlorine pesticide multi-residues in Astragalus
      membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Panax notoginseng
      (Burk.) F. H. Chen and P. quin quefolium L].
AB  - OBJECTIVE: To determine 15 organochlorine pesticide residues in Astragalus
      membranaceus, Panax notoginseng and P. quinquefolium. METHODS: The 15
      organochlorine pesticides were extracted from samples with mixed solvents by
      ultrasonication, cleaned up by a column packed with Florisil, and then separated
      by capillary gas chromatography with electron capture detector(CGC-ECD). The
      capillary column was DB-5(15 m x 0.32 mm x 0.25 microns); injector temperature
      240 degrees C; detector temperature 320 degrees C; the column temperature program
      initial 100 degrees C (hold 0.5 min), rate of 20 degrees C min-1 to 210 degrees C
      (hold 0.5 min), rate of 8 degrees C min-1 to 240 degrees C (hold 10 min). The
      column head-pressure was 58.84 kPa. The injection was splitless and the injection
      volume was 1 microliter. RESULT AND CONCLUSION: The average recoveries and RSD
      are in the range of 78.30%-130.1% and 0.75%-31.9% at two spiked mixed
      organochlorine pesticide levels, respectively. All the samples have
      organochlorine pesticide residues.

PMID- 12515221
TI  - [Determination of flavonoids in Ginkgo biloba L. leaves from different producing
      areas].
AB  - OBJECTIVE: To compare the contents of flavonoids in the leaves of Ginkgo biloba
      gathered from 35 producing areas. METHODS: Separating and determining 3 flavonoid
      aglycones, quercetin, kaempferol and isorhamnetin, by high performance liquid
      chromatography, and there by calculating the total contents of flavonoids.
      RESULTS: The contents of flavonoids in the leaves of G. biloba gathered from
      different producing areas are different, but in those gathered from Pizhou,
      Zheng'an Xing'an, Anlu, etc. appear higher.

PMID- 12515222
TI  - [A new ecdysone hormone rhaponticum from Rhaponticum uniflorum (L.) DC].
AB  - OBJECTIVE: To study the chemical constituents of Rhaponticum uniflorum. METHOD:
      Solvent extraction, separation by silica gel column chromatography and
      identification by physico-chemical properties and spectral data. RESULT: A new
      ecdysone hormone, rhaponticum (1) was isolated from the root of R. uniflorum
      together with a known compound ecdysterone(2). CONCLUSION: The two compounds were
      obtained from the plant for the first time.

PMID- 12515223
TI  - [Studies on chemical constituents in the root of Desmos grandifolius (I)].
AB  - OBJECTIVE: To investigate new compounds with anti-tumor activities from the root
      of Desmos grandifolius of Annonaceae. METHOD: The chemical constituents were
      isolated by silica gel column chromatography, and the structures were elucidated
      by UV, IR, MS, 1H NMR, 13C NMR, H-H COSY and NOESY analysis. RESULTS: Six
      compounds have been isolated from the CHCl3 extract of this plant and identified
      as lawinal(I), isolawinal(II), desmethoxymatteucinol(III), benzoic acid(IV), beta
      sitosterol(V) and sitgmasterol (VI). CONCLUSION: All compounds were found from
      this plant for the first time. Three dihydroflavonoids isolated from this species
      are characterized by A-ring substitution and no B-ring substitution.

PMID- 12515224
TI  - [Studies on chemical constituents of Lagopsis supina (Steph.) Ik.-GaI].
AB  - OBJECTIVE: To study the chemical constituents of Lagopsis supina. METHOD:
      Compounds were separated by solvent extraction, column chromatography and TLC,
      and the structures were determined by chemical and spectral analyses. RESULTS:
      Six compounds were isolated from the ethanol extract of L. supina and identified
      as eicosanoic acid octadecyl ester, eicosanoic acid-16-methyl-15, 16-hetadecenyl
      ester, palmitic acid, beta-sitosterol, oleanolic acid and daucosterol.
      CONCLUSION: Except beta-sitosterol, all the compounds were isolated from this
      genus for the first time.

PMID- 12515225
TI  - [Determination of total flavonoids and dihydromyricetin in Ampelopsis
      grossedentala (Hand-Mazz) W. T. Wang].
AB  - OBJECTIVE: To establish a method for the assay of total flavonoids and
      dihydromyricetin in A. grossedentala. METHOD: The flavonoids were determined by
      spectrophotometry and dihydromyricetin by TCL-scanner. RESULT: The content of
      flavonoids was 43.4%-44.0%, RSD 1.56%-2.62% and the content of dihydromyricetin
      was 37.4%-38.5%, RSD 1.85%-2.65%. CONCLUSION: The method is rapid, simple,
      accurate and good for the determination of total flavonoids and dihydromyricetin
      in A. grossedentala.

PMID- 12515226
TI  - [Effect of L-dicentrine on contraction of rat stomach muscle strips].
AB  - OBJECTIVE: To study the effect of L-dicentrine on the contraction of rat stomach
      muscle strips induced by 5-HT, histamine K+ and Ca2+. METHOD: In-vitro
      experimenting on rat stomach muscle strips. RESULTS: The contraction of the
      strips induced by 5-HT histamine K+ and Ca2+ after high K+ depolarization was
      markedly inhibited by L-dicentrine or papaverine, showing a non-competitive
      antagonism. The contraction induced by 5-HT was inhibited by L-dicentrine in Ca2+
      free solution. L-Dicentrine inhibited the contraction induced by 5-HT, depending
      on Ca2+ released from the intracellular store. When the Ca2+ concentration in
      both solutions was restored, L-dicentrine did not influence the contraction
      significantly. CONCLUSION: L-Dicentrine could relax the rat stomach smooth
      muscle. In rat stomach smooth muscles there exist 5-HT receptors.

PMID- 12515227
TI  - [Preliminary study on apoptosis of BEL-7402 cells induced by Chinese herbs for
      warming yang and dispersing stasis].
AB  - OBJECTIVE: To investigate the antitumor mechanism of Chinese herbs for warming
      yang and dispersing stasis and observe the action of these herbs in inducing
      apoptosis of BEL-7402 cells. METHOD: Apoptosis of BEL-7402 cells induced by the
      above-said herbs was detected through fast red tablet staining, flow cytometry
      and terminal uridine deoxynucleotidyl and labeling (TUNEL). RESULT: After
      treating BEL-7402 cells with the herbs typical apoptosis characteristics could be
      seen under light microscope and TUNEL positive cells were detectable. The
      apoptotic rate was 13.9% (drug concentration 0.5%) and 21.6% (drug concentration
      1%) CONCLUSION: Chinese herbs for warming Yang and dispersing stasis could induce
      apoptosis of BEL-7402 cells and this effect depends on drug concentration.
      Inducing the apoptosis of tumor cells may be part of the mechanism displayed by
      Chinese herbs for warming Yang and dispersing stasis in treating hepatoma.

PMID- 12515228
TI  - The power of positive communication: a 21st century imperative.

PMID- 12515229
TI  - Circle communication: an old form of communication useful for 21st century
      leadership.
AB  - Circle communication is a form of group exchange that builds a network of
      relationships, a sense of community. Through practices of active listening,
      intentional speaking, and conscious self-monitoring, circle communication
      emphasizes individual contribution while building consensus to fulfill the
      purpose of the group. In this regard, circle communication supports a shared
      leadership in which all individual and unique perspectives are engaged to create
      the common ground for action. Circle communication emerges from a shared
      humanity, which can balance the "division of labor" and people only being known
      by their specific organizational roles. Both are needed to sustain an
      organization. By nurturing the human side, regardless of role and function,
      circle communication intersects with diversity or the uniqueness of each
      individual, storytelling, coaching, guiding, and mentoring, as well as
      discovering and responding to conflict.

PMID- 12515230
TI  - Reflections and projections on nursing.
AB  - The author looks at the environment within which nurses work and the services
      that are being delivered in the health care delivery system. These observations
      serve as the background for predictions about what nursing must do and become to
      honor its stewardship to the public. Today's environment is consumer driven,
      multicultural, and multigenerational. The consumer expects information and
      reserves the right to make decisions on his or her own behalf. It remains up to
      nursing to read the cues correctly and use the resources that the consumer brings
      to the nurse-patient relationship. Nurses have the innate skills to fill this
      role, turning dependency to self-care. Care in the new millennium is
      characterized by integrated systems, electronic and computer technology,
      specialization, and inter/transdisciplinary practice. The transition to more
      community-based services makes independent decision making essential.

PMID- 12515231
TI  - 21st century leadership challenge: creating and sustaining healthy, healing work
      cultures and integrated service at the point of care.
AB  - This article addresses the call coming from both those who give and those who
      receive health care to create healthy, healing work cultures and integrated
      service at the point of care. The legacy of leadership will be determined by the
      ability to co-create the best places to practice and receive care. The complexity
      and nature of the work and the outcomes are based on almost two decades of
      "wisdom from the field" coming from a unique consortium of more than 100 rural,
      community, and university settings, as well as feedback from colleagues in more
      than 1,000 organizations.

PMID- 12515232
TI  - Changing managed care to care management: innovations in nursing practice.
AB  - This article describes ways to develop a Case Management System that includes the
      principles of care planning by using an interdisciplinary team across the
      continuum of health services.

PMID- 12515233
TI  - 21st century rural nursing: Navajo Traditional and Western medicine.
AB  - Past experiences enhance the future. Health care providers gaining expertise in
      creative thinking, traditional medicine, spirituality, and cultural sensitivity
      is an essential requirement for 21st century health care. We must stay mindful
      that poverty, isolation, and rural living may create new forms of social
      exclusion because of lack of communication and rapidly changing technology.
      Conversely, sensory overload resulting from a faster paced lifestyle and rapid
      enhancements in technology may cause increased tension and stress. This article
      reviews successes that may offer the reader ideas on coping with the provision of
      health care services in such a volatile changing environment, while honoring
      tradition and cultural competency.

PMID- 12515234
TI  - Nursing case management in the 21st century: intervening where margin meets
      mission.
AB  - Case management, the basic process of matching key resources to individual's
      needs, often carried out across time and place, has been a relatively low-profile
      function (under various levels) within society, business, and health care for
      many years. Nurses have been involved in case management since its beginnings in
      social service and public health. However, nurses only became prominent as case
      managers during the last half of the 20th century because of the need to
      establish medical necessity for health care payments and, eventually, the need to
      provide discharge planning. The 21st century begins with an evolving core for
      case management functions in health care, the specific models dictated by the
      margins and missions of the employing organization. Case management, in fact, is
      the nursing process applied at a system level. However, if case management is to
      remain an adaptable yet powerful strategy for patients and organizations across
      the continuum of health care, it will have to move beyond access and medical
      necessity functions to those functions that demand advanced nursing experience
      and skills.

PMID- 12515235
TI  - Emergence of the free agent nurse workforce.
AB  - The health care world is changing rapidly and so is its workforce. As nurses are
      welcomed as copartners in care delivery and design, a new relationship between
      employer and employee is forged. Nurses who see themselves as free agents,
      working in partnership with their employers, function within a very different
      employment relationship than in past years. The concept of free agency is more
      familiar to nurses in the Generation X age cohort but is of great interest to all
      nurses and nurse administrators. Free agency is more of a mindset than an
      employment status and is explored in this article.

PMID- 12515236
TI  - Nurse practitioner: reflecting on the future.
AB  - The role of the nurse practitioner was first conceptualized in the late 1960s.
      Today, there are approximately 70,000 nurse practitioners in practice, they
      receive third-party insurance reimbursements, and they are in many specialty
      practices, as well as working in primary care practices promoting health and
      disease prevention. In the future, economics will shape our health care industry,
      placing a greater demand for nurse practitioners in this trillion-dollar
      marketplace. This article explores the evolving role of the nurse practitioner in
      education, practice, and research to meet the challenges of the health care needs
      into the 21st century.

PMID- 12515237
TI  - Healing health care, healing nursing in the 21st century.

PMID- 12515239
TI  - Lawyers win, patients lose.

PMID- 12515238
TI  - Thanks, TSBME.

PMID- 12515240
TI  - A vote for mental health.

PMID- 12515241
TI  - Sample medications can help those in need.

PMID- 12515242
TI  - When protected information can be released.

PMID- 12515243
TI  - Rx battle.

PMID- 12515244
TI  - Much ado about experts.

PMID- 12515245
TI  - Laboring over midwives.

PMID- 12515247
TI  - Declaration for health.

PMID- 12515246
TI  - Protecting angels of mercy.

PMID- 12515248
TI  - A study of hepatitis A seropositivity in Dallas County, Texas, 1998 through 1999.
AB  - This paper provides background information on the epidemiology and a descriptive
      analysis of infection with hepatitis A virus in Dallas County, Texas, for 1998
      and 1999. Reported cases were obtained from the Dallas County Health Department,
      and incidence rates per 100,000 population were calculated. Persons who tested
      seropositive for hepatitis A virus between January 1, 1998, and December 31,
      1999, were included. Variables of interest included age, sex, race, and date of
      occurrence. The overall incidence rate of this infection in Dallas County for
      1998 was 1.9 times higher than that of the United States; in 1999, the overall
      rate for Dallas County increased by more than 1.6 times. Rates were significantly
      higher among males, highest among Hispanics, and lowest among blacks for both
      years. Incidence rates among age groups varied between years by increasing in
      people 50 years and older from 1998 to 1999 as a result of a single cafeteria
      related outbreak of 150 cases in March 1999. Infection with hepatitis A virus
      remains the most reported vaccine-preventable disease in the United States.

PMID- 12515249
TI  - Sex and ethnic differences in hip fracture-related mortality in Texas, 1990
      through 1998.
AB  - Hip fracture, the most serious complication of osteoporosis, is associated with
      considerable morbidity and mortality. Knowledge of hip fracture-related mortality
      rates by age, sex, and ethnicity as well as temporal changes in mortality are
      important for health planners to implement programs aimed at awareness and
      prevention of hip fractures. This study determines adjusted death rates in Texas
      by age, sex, and ethnic group from 1990 through 1998 and describes trends in
      mortality during the 9-year period. Upward trends in mortality were observed for
      both sexes in whites and blacks. Hispanics showed trends toward decreasing
      mortality rates. The highest mortality rates were observed in whites,
      predominantly in persons 80 years and older. Furthermore, rates in men by ethnic
      group consistently exceeded those in women. As the population ages, hip fractures
      are becoming a major public health problem in Texas that will likely increase
      unless fall prevention strategies and treatment of osteoporosis in elderly people
      are improved.

PMID- 12515251
TI  - The community of research in medical education.

PMID- 12515252
TI  - The oral brush biopsy: a step forward?

PMID- 12515253
TI  - Meta-analysis of associations of the Ser217Leu and Ala541Thr variants in ELAC2
      (HPC2) and prostate cancer.

PMID- 12515254
TI  - Regarding "Testing for population subdivision and association in four case
      control studies".

PMID- 12515255
TI  - The ABCA4 gene in autosomal recessive cone-rod dystrophies.

PMID- 12515256
TI  - Experts confirm statins' safety but advise caution with certain patients.

PMID- 12515257
TI  - Bibliography of Toxinology.

PMID- 12515258
TI  - Inhaled corticosteroids are safe even for young asthma patients.

PMID- 12515259
TI  - Study boosts argument for beta-blockers after heart surgery.

PMID- 12515260
TI  - Chronic disease self-management program reduces costs and improves functionality.

PMID- 12515261
TI  - Cryptic chromosome rearrangements detected by subtelomere assay in patients with
      mental retardation and dysmorphic features.
AB  - The regions near telomeres of human chromosomes are gene rich. Chromosome
      subtelomere rearrangements occur with a frequency of 7-10% in children with mild
      to-moderate mental retardation (MR) and approximately 50% of cases are familial.
      Clinical investigation of subtelomere rearrangements is now prompted by
      fluorescence in situ hybridization (FISH) analysis using specific DNA probes from
      all relevant chromosome ends. In our study, 40 children were selected for
      subtelomere assay using either the Chromophore Multiprobe-T Cytocell device or
      the VYSIS TelVision probes. Inclusion criteria were: developmental delay or MR; a
      normal 550 G-band karyotype; FRAXA negative; and at least one other clinical
      criterion. Exclusion criteria included an identified genetic or environmental
      diagnosis. Of the 40 patients analysed, four (10%) were found to have subtelomere
      rearrangements. Three of 40 (7.5%) were found to have an unbalanced subtelomere
      rearrangement and one of 40 (2.5%) was found to have an apparently normal variant
      subtelomere deletion. The first of the three with an unbalanced karyotype was the
      result of a familial translocation, the second was a de novo finding, and the
      origin of the third could not be determined. The subtelomere FISH assay detected
      almost twice the frequency of unbalanced karyotypes as those detected by 550 G
      banding in our cytogenetics laboratory (4.7%). In addition, subtelomere screening
      was eight times more likely than fragile X screening in our DNA laboratory (1%)
      to detect genetic abnormalities in mentally handicapped individuals. Our findings
      support the view that screening for subtelomere rearrangements has a greater
      positive yield than other commonly used genetic investigations and, if cost and
      resources permit, should be the next diagnostic test of choice in a child with
      unexplained MR/dysmorphisms and a normal 550 G-band karyotype.

PMID- 12515262
TI  - Development and implementation of an HIV/AIDS case management outcomes assessment
      programme.
AB  - The Case Management Section of the New York State Department of Health AIDS
      Institute coordinates the provision of case management services for people living
      with HIV/AIDS throughout the state. The Community Follow-Up Program (CFP),
      providing intensive case management for HIV-positive individuals and their
      families, operates under the auspices of the Case Management Section. This
      article focuses on a public/private outcomes assessment partnership, sponsored by
      the Case Management Section, and developed in conjunction with a team of CFP
      programme managers from across the state. The process used to develop outcome
      indicators and measures is described; challenges encountered along the way are
      detailed; and suggestions for other public/private partnerships are outlined.
      Results from two years of outcomes data collection are also presented. The
      article concludes that the inclusion of providers in the identification and
      measurement of desired outcomes can help overcome provider resistance to outcomes
      assessment and can help ensure that outcomes data are used to improve programme
      performance.

PMID- 12515263
TI  - [Apothecaries' exercise by widows of apothecaries from the XVth to the XVIIIth
      centuries].
AB  - As far as we study the rules of the apothecaries' communities, the widow of an
      apothecary was allowed to keep the shop as long as she lived alone, with the help
      of a servitor judged to be efficient and valuable by the apothecaries' community.
      The first statutes appeared in the XVth century; they were more and more numerous
      in the XVIth and especially in the XVIIth century. The conditions of the widows'
      privileges remained nearly the same all over France during this period.

PMID- 12515264
TI  - [Pharmacy and art: Turkish's shadows and colors].
AB  - Karagoz is the name of the Turkish shadow theater and in the same time the name
      of the principal hero: it means "black eye". This burlesque show was performed on
      great occasions, such as births, circumcisions, weddings, and also during the
      winter evenings and the month of Ramadan. The size of puppets, in camel hide, is
      generally 25/35 cm. Sketches are inspired by daily life in big anatolian cities
      and in Istanbul. In this play, Karagoz is both pharmacist and doctor, a job for
      which he is not at all qualified. Of course, the farce is embroidered around his
      extravagant speeches and acts when different people come in the pharmacy. We
      notice the importance of the French vocabulary.

PMID- 12515266
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States, 2002-03 season.

PMID- 12515265
TI  - From the Centers for Disease Control and Prevention. Hepatic toxicity possibly
      associated with kava-containing products--United States, Germany, and
      Switzerland, 1999-2002.

PMID- 12515267
TI  - From the Centers for Disease Control and Prevention. Invasive cervical cancer
      among Hispanic and non-Hispanic Women--United States, 1992-1999.

PMID- 12515268
TI  - [Art nouveau: pharmacy shops in Nancy].
AB  - At the beginning of the 20th century, an important artistic activity develops in
      Nancy. The "Ecole de Nancy" transforms a provincial city into one of the
      metropolis of "Art Nouveau". The pharmacists participate at the activity of their
      town and eight of them choose the new style for their pharmacy. In 1902,
      Rosfelder is the first to modify his shop, and later, Jacques, Delidon, Mouzin,
      Godfrin brothers, Monal and Fandre, before, during and after the First World War,
      have a same step. For the ornament, the artists use plants derived from local
      medicinal flora. "Art Nouveau", adept of curves, appears to be ideal to symbolize
      vegetable kingdom. In these pharmacy shops, fine arts join materia medica.

PMID- 12515269
TI  - Current status of lung transplantation in Japan.

PMID- 12515270
TI  - [Accommodative intraocular lenses. Can synthetic lenses accommodate?].

PMID- 12515271
TI  - [Asthenoscopic problems with a subconjunctival worm].

PMID- 12515272
TI  - Today's regional distribution of echinococcosis in China.
AB  - OBJECTIVE: To review the current regional distribution of echinococcosis in China
      for the purpose of providing the scientific data for the control of
      echinococcosis in the future. DATA SOURCES: All data in this paper were
      originated from related references in Chinese or English language Chinese
      journals except one from Lancet. STUDY SELECTION: Thirty-one original articles
      published from 1983 - 2001 were selected according to the stated purpose and 7 of
      them were written by the author. DATA EXTRACTION: The present paper addresses
      cystic echinococcosis (CE) and alveolar echinococcosis(AE), as well as their
      respective regional distribution. RESULTS: CE was distributed chiefly in Western
      China where Gansu, Xinjiang, Qinghai, Ningxia, Inner Mongolia, Tibet, west
      Sichuan and Qingzang plateau were hyper-endemic areas. Regional distribution of
      AE was not so extensive as that of CE, but it was found mainly in northwest China
      as well. Moreover, AE was extremely harmful to human body and "AE cancer" is
      popularly called. CONCLUSION: Steps should be taken in the future heath policy to
      control its spread. Regional distribution of echinococcosis is so extensive in
      China that CE and AE should be increasingly controlled today.

PMID- 12515273
TI  - CTLA-4 gene A/G polymorphism associated with diabetes mellitus in Han Chinese.
AB  - OBJECTIVE: To investigate the association of cytotoxic T lymphocyte-associated
      antigen 4 (CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus
      in Han Chinese. METHODS: An A/G transition at position 49 of exon 1 was analyzed
      in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36
      controls were analyzed by polymerase chain reaction-restriction fragment length
      polymorphism analysis. RESULTS: A highly significant increase in the frequency of
      the G allele was seen in patients with type 1 diabetes compared with controls
      (66.1 % vs. 34.7%, respectively; P < 0.0005; OR = 3.670) . This reflected an
      increase in the GG genotype in patients (48.4% vs. 22.2%, respectively; P =0.025;
      OR =3.281) and a significant decrease in the AA genotype (16.1 % vs. 52.8%,
      respectively; P = 0.002). The allele frequencies of A and G in patients with type
      2 diabetes were not significantly different from controls(A/G, 50.0/50.0% vs.
      65.3/34.7%; P = not significant) . The distribution of genotype, however,
      differed significantly. This difference reflected an increase in the AG genotype
      in patients (54.8% vs.25.0%, respectively; P=0.012; OR=3.643) and a decrease in
      the AA genotype (22.6% vs. 52.8%, respectively; P=0.011). CONCLUSIONS: CTLA-4 49
      AA is protective from diabetes mellitus, whereas, CTLA-4 49 G allele (both as
      homozygotes and as heterozygotes ) confers an increased risk of diabetes
      mellitus.

PMID- 12515274
TI  - Expression and significance of the vascular permeability factor in nasal polyps.

PMID- 12515275
TI  - [Acute loss of vision with painful, unilateral exophthalmos].

PMID- 12515276
TI  - Health service needs of women with reproductive tract infections in selected
      areas of China.
AB  - OBJECTIVE: To provide insight into the psychosocial factors underlying the
      utilisation of health services by women with reproductive tract infection (RTI)
      symptoms. METHODS: A cross-sectional study, adopting Aday and Andersen' s Social
      Behaviour Model, was conducted between 1998 and 1999 in Chinese Hebei province
      and Beijing. A total of 864 eligible married women (age 21 to 60 years) were face
      to face interviewed. RESULTS: The percentage of self-reported symptoms of RTIs in
      urban and rural women was 35.6 and 46.8, respectively; the proportion of women
      with RTIs who utilised health services was 27.5% and 26.7%, respectively.
      Compared to urban women, rural women had less knowledge on RTIs and more
      traditional beliefs, and were more satisfied with local health services. The
      results of logistic regression analysis showed that the common factor influencing
      health service utilisation in women with RTIs was current experience of RTIs.
      Knowledge about self-medication, perceived social stigma attached to RTIs, prior
      experience of RTIs, family income and perceived severity of RTIs were also
      predictors of utilisation of health services in rural women with RTIs.
      Satisfaction with health providers, information received from health providers,
      prior experience of RTIs, occupation and medical care coverage were predictors of
      utilisation of health services in urban women with RTIs. CONCLUSION: The
      prevalence of RTIs is high, but the rate of seeking health services is low. There
      is a great need for emphasizing culturally acceptable reproductive health
      education in different places to improve women' s ability for self-care. Regular
      medical check-ups for women are also important. It is necessary to improve the
      quality of health service, complete the reform of health insurance and alleviate
      women' s social stigma related to RTIs, giving women social and moral support.

PMID- 12515277
TI  - Management of autonomic hyperreflexia during cesarean section in a woman with
      spinal cord injury: a case report.

PMID- 12515278
TI  - [Emetine and quinine, a therapy to rescue Bellini in 1835].
AB  - At the moment when his operas got a European celebrity, Vincenzo Bellini born in
      1801 rapidly died in September 1835 after a three weeks digestive illness, with
      mainly dysenteria. Young and healthy, this unexpected event questioned the
      authorities in Paris. The post mortem examination showed that the colonic mucosa
      was covered by numerous ulcers, and that a large abcess existed in the liver. All
      other parts of the body were absolutely sound. These results came out from the
      autopsy performed by Adolphe Dalmas (1799-1844), professor agrege at the Faculty
      of medicine of Paris, formerly member of the special committee in charge of
      fighting the cholera in 1831 and 1832, who studied its medical aspects during the
      epidemic attack in Russia, Poland, Germany and Great Britain. With a wide
      knowledge in the field of the intestinal pathology, his conclusions established
      that the death came from an inflammation of the bowel, excluding clearly any
      touch of cholera or poisoning. Nowadays, it is obvious that this dysenteria
      syndome associated to such anatomic disorders would belong to the chronic amebic
      disease. Probably contaminated in 1828, Bellini developed a severe episode in
      1830, necessitating a long rest during several months, spent at Moltrasio along
      the side of the Lake of Como. At the time, he composed La Sonnambula and Norma.
      In 1833 after staying in London from April to August, he came to Paris preparing
      a new work I Puritani (The Puritains). At summer time, he usually suffered slight
      recurring episodes, that he treated by applying vesicatories. For frequent
      periods, he lived outside Paris in a villa standing along the Seine in Puteaux
      rented by his British friends the Levys. Early in September 1835, these symptoms
      came again and and suddenly worsened with pain, fever and loss of rest at night.
      Deserted and lonely as the Levys often left the villa, his critical condition
      exhibiting tremendous sufferings led to death on the 23rd of September. During
      the final days, he was not granted any relevant medical support, except the poor
      cares given by the Italian physician Montallegri, not authorised at that time to
      practice in France. As emetine and quinine since 1822 were both available as pure
      alcaloids, produced by the pharmacist Joseph Pelletier, it is assumed that
      Bellini might have recovered after an intensive treatment implementing these
      substances by oral, local and rectal routes (enemas and suppositories). At that
      time, apart from the academic teaching inherited from Broussais, the tropical
      practitioners currently used them in the treatment of dysenteria and tropical
      liver abcesses (Annesley, Segond and Dutroulau), as decocted ipeca roots and
      cinchona barks. Later on when the amebic disease has gained its proper
      nosography, the clinicians underlined the dangerous and unpredictable issues of
      the hyperacute hepatic syndromes, unexpected and occurring by apparently healthy
      individuals. By 1960, its treatment was still obtained by the emetine
      derivatives.

PMID- 12515279
TI  - Gallbladder tuberculosis: case report.

PMID- 12515280
TI  - Craniopagus twins.

PMID- 12515281
TI  - Unriddling the role of matrix metalloproteinases in human cerebral stroke.

PMID- 12515282
TI  - [Prosecution of Melanie Hahnemann in 1847 at the court of Paris: illegal practise
      of pharmacy and medicine].
AB  - Recently married, the Hahnemanns came to Paris in 1835. The great man, 80, was
      authorised to practice in France. His wife Melanie always assisted him in writing
      prescriptions, and in recruiting patients. When he died in 1843, she was
      continuing to practise assisted or not by a physician, Deleau or Croserio. A
      young pharmacist, Charles LeThiere, lived close to her as her adoptive son,
      grandson of the famous painter Guillaume Guillon-LeThiere who was the director of
      the French Academy of Fine Arts of Rome at the Villa Medici, grandson as well of
      the Roman pharmacist Giuseppe Meli. Early Charles remained orphan and was
      educated by Melanie. In 1844, he obtained his pharmaceutical graduation at the
      Ecole superieure de Pharmacie de Paris. In 1847, she was accused of illegal
      practising of medicine and pharmacy. She claimed that she held the degree of
      doctor in homeopathy granted to her by the Academy of Pennsylvania. The court
      condemned her on the medical side considering that she earned money without legal
      certification in medicine. But as the drugs were prepared by a pharmacist, and
      delivered free of charge to the patients, no sentence was pronounced against her
      neither against LeThiere. However, the court tempted to object that LeTiere did
      not meet all the legal requirements for practising his pharmaceutical activity,
      especially aruging that he did not own an open shop of pharmacy, and that he did
      not declare his activity to the authorities in Paris. This point underline the
      fact that during the XIXth century the French law (21 germinal An XI- 1803),
      obliged the starting drug industry to be in dependence of the shops of pharmacy
      opened to the public, owned by a graduated pharmacist. As defender Mrs. Hahnemann
      chose the quite known solicitor Chaix d'Estange. Many testimonies came for
      justifying her capability of medical prescribing from artists, officers, writers
      and several aristocrats. From abroad came the supports of American doctors,
      Hempel, Hering and Hull. But the core question motivating her sentence came from
      the medical lobby acting in Paris led by the professor Orfila. Among the adepts
      of the homeopathy themselves, raised division and rivalry, but all considering
      that Melanie Hahnemann's behavior was criticable. The court fined her for hundred
      francs that she paid. Then, she kept the circle of her friends and continued in
      medical counselling.

PMID- 12515283
TI  - Autoimmune hepatitis: the way we were, the way we are today and the way we hope
      to be.

PMID- 12515284
TI  - Is pregnancy a model how we should control some autoimmune diseases?
AB  - Pregnancy and parturition are the physiological conditions that affect the course
      and severity of numerous autoimmune diseases. If genotype might be primarily
      considered as a determinant of whether or not autoimmunity develops, clinical
      heterogeneity of the disease might arise from the interaction of the genotype and
      the environment. Numerous external factors with extremely important
      immunoregulatory properties, including hormones, affect an in vivo open complex
      immune system. The further investigation of the role of neuroendocrine
      immunological network, including a pregnancy-associated immunomodulation, as much
      as the role of "causative" or "trigger" agents, may allow the rational basis of
      new alternative treatment of numerous autoimmune diseases.

PMID- 12515285
TI  - Peripheral blood lymphocyte transformation to G2s in patients with autoimmune
      thyroid disease with and without ophthalmopathy.
AB  - Thyroid associated ophthalmopathy (TAO) is an autoimmune disease involving the
      extra ocular muscles and surrounding orbital connective and adipose tissues. The
      mechanism for the link between ophthalmopathy and thyroid autoimmunity is unknown
      but current evidence favors an immune reaction against a thyroid and orbital
      tissue shared antigen such as the novel protein G2s, which is highly expressed in
      both eye muscles and thyroid, or the TSH receptor (TSHR). Earlier, we showed that
      serum antibodies against G2s were closely linked to ophthalmopathy. Although
      lymphocytic infiltration of the eye muscles is a pathologic feature of TAO, it is
      unclear whether the reaction is in the eye muscle fiber or the surrounding
      connective tissue. We tested for peripheral blood mononuclear cell sensitization
      to G2s fusion protein in patients with TAO, Graves' hyperthyroidism or
      Hashimoto's thyroiditis without evident ophthalmopathy and normal subjects.
      Results were expressed as counts per min (cpm) and as stimulation indices (SI).
      Although proliferation tests were positive in 23% of patients with TAO, overall,
      there were no significant differences between the four groups. Tests were also
      positive in four out of seven patients with Hashimoto's thyroiditis, suggesting
      that immune reactivity against G2s could be a marker of this progressive thyroid
      disorder. There was no significant correlation between T cell reactivity to G2s
      and serum antibodies against the same protein, measured in enzyme linked
      immunosorbent assay. Failure to demonstrate significant T lymphocyte
      sensitization to G2s in the majority of patients with TAO may reflect the small
      number of sensitized T cells expected to be circulating in the peripheral blood
      which could be overcome by testing cloned orbital T cells, as available. Another
      possibility is that the T cell epitope(s) is not present on the 141 amino acid
      fragment of G2s that we have so far cloned. The finding of positive T cell tests
      in a small proportion of patients with ophthalmopathy suggests that future
      studies using cloned orbital T cells and full length G2s, or its dominant
      epitope, are indicated.

PMID- 12515286
TI  - Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis.
AB  - In the last two decades, atopic dermatitis (AD) has been of increasing clinical
      significance in Japan. Eight-20% of patients with AD developed progressive
      cataracts (cataract-AD) and lens epithelial cells (LECs) were severely damaged.
      Lens epithelium-derived growth factor (LEDGF) is a newly isolated survival
      factor. In the presence of LEDGF, LECs survive well and in the absence of LEDGF,
      they become highly susceptible to stress. We investigated (1) whether auto
      antibody (auto-Ab) to LEDGF is present in sera of AD patients and (2) whether
      depletion of LEDGF by the auto-Ab kills LECs. In sera from 26 patients with AD
      using ELISA, we found significantly higher levels of auto-Ab to LEDGF than that
      in a normal control group. Affinity purified auto-Ab to LEDGF from these sera
      killed LECs without complement activation. Levels of histamine in the AD group
      were significantly higher and levels of prostaglandin E2 were significantly lower
      than in the normal group. However, statistically there are no differences between
      sera from AD and cataract-AD in levels of Ab to LEDGF, histamine, prostaglandin
      E2 (PGE2), immunoglobulin E (IgE) and eosinophiles. We speculate that cataract-AD
      may be induced, in part, by a combination of high levels of serum histamine and
      eye rubbing which could break the blood-aqueous barrier to allow the entry of Ab
      to LEDGF into the privileged compartment, thus, reducing LEDGF levels, resulting
      in damage to LECs, and cataract formation.

PMID- 12515287
TI  - Adrenalitis in the non-obese diabetic mouse.
AB  - The non-obese diabetic (NOD) mouse is a model of spontaneous type-1 diabetes used
      in the field of diabetes research. This study looked at the adrenal glands of NOD
      and control mice both indirectly in vivo for hormone secretion, and directly in
      vitro for histological examination. Adrenal glands were taken from NOD mice, of
      both sexes, at different ages and corticosterone and adrenocorticotropic hormone
      (ACTH) plasma levels evaluated by radioimmunoassay. There was evidence of
      lymphocytic infiltration of the adrenal glands, which however, was not
      accompanied by changes in corticosterone levels. There was a reduction in ACTH
      levels with age (R2 = 0.98). Mice from other strains (TFW, CBA and Balb/c) showed
      no lymphocytic infiltration in the adrenal glands and had lower levels of
      corticosterone than NOD mice of similar ages, but the differences were not
      significant. In conclusion, since the NOD mouse shows histological signs of
      adrenalitis, thyroiditis, sialitis and parathyroiditis, this animal can be
      regarded as a model to investigate mechanisms involved in diffuse lymphocytic
      infiltration of peripheral endocrine glands (polyendocrine autoimmunity). In
      addition, if diabetes in the NOD mouse is the result of a polyendocrine disorder
      rather than a process specific for diabetes, then this finding may have
      implications for attempts to prevent type-1 diabetes in humans.

PMID- 12515288
TI  - Immune reactivity to GAD25 in type 1 diabetes mellitus.
AB  - While both isoforms of glutamic acid decarboxylase (GAD) function as important
      autoantigens in autoimmune diabetes mellitus-GAD65 in humans and GAD67 in the NOD
      mouse-GAD67 is not synthesized in human pancreatic islets and is thought not to
      be an autoantigen in human diabetes. We have recently shown, however, that human
      islets contain a GAD67 splice variant: GAD25. Given the evidence that GAD67 could
      be a key diabetogenic autoantigen in the NOD mouse and the high prevalence of
      GAD65 autoantibodies in human type 1 diabetes, it became important to ask whether
      there is also immune reactivity to GAD25 in type 1 diabetes-possibly implicating
      it in the pathogenesis of the disease-and whether GAD25 reactivity could, like
      GAD65 reactivity, function as a clinically useful marker for the disease. We also
      hypothesized that the presence of autoantibodies to the smaller splice variant
      could be a cause of the up to 30% prevalence of GAD67 autoreactivity associated
      with type 1 diabetes. We therefore analyzed GAD25 reactivity in 105 newly
      diagnosed children with type 1 diabetes and 74 control subjects. While 14 (13%)
      of the diabetic subjects were positive for GAD67 autoantibodies, only 3 (3%) were
      positive for GAD25 reactivity, none of which were GAD67 antibody-positive.
      Analysis of reactivity to a GAD67 chimera was consistent with GAD67 binding
      activity being due to cross-reactive GAD65 antibodies. Immunostaining confirmed
      the presence of GAD25 in human islets, revealing GAD25-positive cells to be
      sparse. Our results indicate that autoreactivity to GAD25 is rare in newly
      diagnosed type 1 diabetes and does not underlie GAD67 reactivity.

PMID- 12515289
TI  - Isolation and characterization of human monoclonal autoantibodies to glutamic
      acid decarboxylase.
AB  - Production of human monoclonal autoantibodies to glutamic acid decarboxylase M(r)
      65,000 (GAD65), characterization of their isotype, binding affinity, V region
      sequences and competition with autoantibodies in patients' sera is described.
      Lymphocytes from a patient with Addison's disease who had GAD65 autoantibodies
      without diabetes were immortalised and fused to a mouse/human hybridoma. In
      addition, mouse monoclonal antibodies to GAD65 were produced using standard
      techniques. F(ab')2S from our monoclonals and the GAD6 mouse monoclonal were used
      in competition with intact monoclonals and sera from diabetic patients for
      binding to 125I-labelled GAD65 (amino acids 46-586). Reactivities of the human
      monoclonals with GAD 65,000/67,000 M(r) chimeras were also studied. Variable
      region genes of human monoclonals were sequenced and analysed. The human
      monoclonals (n = 3) had affinity constants for GAD65 of 2.2 x 10(9), 5.8 x 10(9),
      1.3 x 10(10) mol/l(-1); affinities of the mouse monoclonals (n = 5) ranged from
      1.1 x 10(8) to 5.4 x 10(10) mol/l(-1). The binding of each of the human
      monoclonals was inhibited by GAD6 F(ab')2 and the binding of GAD6 antibody was
      inhibited by the human monoclonal F(ab')2S suggesting that the epitopes for these
      antibodies were overlapping. Studies with GAD65/GAD67 chimeras indicated that the
      human monoclonals reacted with C-terminal epitopes. The human monoclonals, GAD6
      and 3/5 mouse monoclonals inhibited serum autoantibody binding to 125I-labelled
      GAD65. Overall, the human monoclonals were of high affinity, reacted with C
      terminal epitopes and showed evidence of antigen driven maturation; they
      represented only a proportion of the repertoire of autoantibodies to GAD65 in the
      donor's serum and in the sera of patients with type-1 diabetes.

PMID- 12515290
TI  - Factor XIII and tissue transglutaminase antibodies in coeliac and inflammatory
      bowel disease.
AB  - Tissue transglutaminase (tTg) has been identified as an autoantigen in coeliac
      disease (CD). There is a marked homology between different forms of
      transglutaminase, such as tTg and coagulation factor XIII. We compared titres of
      both IgA- and IgG-antibodies against these two antigens in 20 CD patients, 20
      endomysial antibody (EMA)-negative controls and a group with inflammatory bowel
      disease (34 with Crohn's disease and 23 with ulcerative colitis). IgA-antibodies
      against tTg correlated with EMA titres and had high sensitivity and specificity
      in screening for CD. Only in two CD patients were high titres found of IgA
      antibodies against factor XIII, non-reactive with tTg. Both lacked bleeding
      tendency. The presence of IgG-antibodies against tTg, in contrast, had low
      sensitivity and specificity in screening for CD and were frequently seen in
      inflammatory bowel disease. Similarly, factor XIII IgG-antibodies displayed a non
      specific pattern with modestly elevated titres in patients with Crohn's disease
      and in both EMA-negative and positive patients. Despite a marked homology with
      tTg, the occurrence of high titre IgA-antibodies against factor XIII is
      infrequent in CD, but may-when present-be the result of epitope spreading. The
      presence of IgG-antibodies in CD and inflammatory bowel disease illustrates the
      complexity of autoantibody reactions in gastrointestinal disease.

PMID- 12515291
TI  - Intestinal permeability to mannitol and lactulose in children with type 1
      diabetes with the HLA-DQB1*02 allele.
AB  - Food antigens and enteroviruses are possible triggers of type 1 diabetes. Because
      permeability of the intestinal epithelium may facilitate contact of these
      antigens with the mucosal immune system, we set out to study intestinal
      permeability in patients with type 1 diabetes. Children with type 1 diabetes (n =
      26, mean age 12 years, mean duration of disease 4 years) and 24 healthy age
      matched control children were given mannitol and lactulose orally, and their
      intestinal permeability was measured as a percentage of this dose recovered in
      urine. Patients with type 1 diabetes did not differ in their permeability to
      lactulose, nor was their lactulose/mannitol ratio any different from that of
      controls. However, patients with type 1 diabetes who had the HLA-DQB 1*02 allele
      and, therefore, a higher risk for celiac disease (CD) absorbed significantly more
      mannitol (mean + 95% CI): 17.7% (15.2-20.2) than did those negative for this
      allele: 12.3% (8.2-16.4), p = 0.04. Their lactulose permeability was also higher:
      0.30 (0.16-0.44) and 0.09% (0-0.18), respectively, p = 0.02. Although the
      differences in permeability reach statistical significance, there was still much
      overlap between the two groups in terms of actual laboratory values. The higher
      permeability of patients with the HLA-DQB1*02 allele suggests that these patients
      may be more prone to develop abnormal immune responses to food antigens.

PMID- 12515292
TI  - Attempted treatment of cutaneous lymphomatosis in a ram.

PMID- 12515293
TI  - Plant poisonings and mycotoxicoses of importance in horses in southern Africa.
AB  - Well-known plant poisonings such as 'dunsiekte' (seneciosis) and 'jaagsiekte'
      (crotalariosis) of horses in southern Africa are briefly reviewed. Relatively
      unfamiliar mycotoxicoses such as stachybotryotoxicosis and perennial rye grass
      staggers and potentially occurring exotic intoxications such as equine
      nigropallidal encephalomalacia and ergot alkaloid poisoning are also discussed.
      This article is aimed at informing the southern African equine practitioner about
      probable poisonings that might occur locally in horses.

PMID- 12515294
TI  - Ixodid ticks on cattle belonging to small-scale farmers at 4 communal grazing
      areas in South Africa.
AB  - Ixodid ticks were collected during the period September 1991 to August 1993 from
      cattle belonging to small-scale farmers utilising 4 communal grazing areas. Three
      of these were in North West Province and 1 in Mpumalanga province, South Africa.
      Ten tick species were collected in North West Province and 7 in Mpumalanga. The
      adults of Amblyomma hebraeum, Rhipicephalus appendiculatus and Rhipicephalus
      evertsi evertsi were most numerous in North West Province, while in Mpumalanga
      Boophilus decoloratus comprised more than 75% of the total population. Amblyomma
      hebraeum was present on all grazing areas, and heavy infestations of adults
      occurred during the period October to May on 1 of these. Few B. decoloratus were
      collected in North West Province, chiefly because the sampling method was
      inadequate, and most of these were present during early summer (October to
      December) and late summer and autumn (March to May). The initially low population
      of B. decoloratus in Mpumalanga increased substantially towards the conclusion of
      the survey, probably because of the cessation of dipping. Boophilus microplus was
      present in small numbers on 2 grazing areas in the North West Province. Adult
      Hyalomma marginatum rufipes reached peak numbers from December to February and
      Hyalomma truncatum from February to April in the North West Province. Only H.
      marginatum rufipes was collected in Mpumalanga. Rhipicephalus appendiculatus was
      present on all the grazing areas, with most adults present from December to
      April. Most adult Rhipicephalus evertsi evertsi were collected from September to
      April and Rhipicephalus simus was present during the period October-April.

PMID- 12515295
TI  - The cardiovascular and respiratory effects of medetomidine and thiopentone
      anaesthesia in dogs breathing at an altitude of 1486 m.
AB  - The purpose of this study was to evaluate the cardio-respiratory effects of the
      combination of medetomidine and thiopentone followed by reversal with atipamezole
      as a combination for anaesthesia in 10 healthy German Shepherd dogs breathing
      spontaneously in a room at an altitude of 1486 m above sea level with an ambient
      air pressure of 651 mmHg. After the placement of intravenous and intra-arterial
      catheters, baseline samples were collected. Medetomidine (0.010 mg/kg) was
      administered intravenously and blood pressure and heart rate were recorded every
      minute for 5 minutes. Thiopentone was then slowly administered until intubation
      conditions were ideal. An endotracheal tube was placed and the dogs breathed room
      air spontaneously. Blood pressure, pulse oximetry, respiratory and heart rate,
      capnography, blood gas analysis and arterial lactate were performed or recorded
      every 10 minutes for the duration of the trial. Thiopentone was administered to
      maintain anaesthesia. After 60 minutes, atipamezole (0.025 mg/kg) was given
      intramuscularly. Data were recorded for the next 30 minutes. A dose of 8.7 mg/kg
      of thiopentone was required to anaesthetise the dogs after the administration of
      0.010 mg/kg of medetomidine. Heart rate decreased from 96.7 at baseline to 38.5 5
      minutes after the administration of medetomidine (P < 0.05). Heart rate then
      increased with the administration of thiopentone to 103.2 (P < 0.05). Blood
      pressure increased from 169.4/86.2 mmHg to 253.2/143.0 mmHg 5 minutes after the
      administration of medetomidine (P < 0.05). Blood pressure then slowly returned
      towards normal. Heart rate and blood pressure returned to baseline values after
      the administration of atipamezole. Arterial oxygen tension decreased from
      baseline levels (84.1 mmHg) to 57.8 mmHg after the administration of medetomidine
      and thiopentone (P < 0.05). This was accompanied by arterial desaturation from
      94.7 to 79.7% (P < 0.05). A decrease in respiratory rate from 71.8 bpm to 12.2
      bpm was seen during the same period. Respiratory rates slowly increased over the
      next hour to 27.0 bpm and a further increases 51.4 bpm after the administration
      of atipamezole was seen (P < 0.05). This was maintained until the end of the
      observation period. Arterial oxygen tension slowly returned towards normal over
      the observation period. No significant changes in blood lactate were seen. No
      correlation was found between arterial saturation as determined by blood gas
      analysis and pulse oximetry. Recovery after the administration of atipamezole was
      rapid (5.9 minutes). In healthy dogs, anaesthesia can be maintained with a
      combination of medetomidine and thiopentone, significant anaesthetic sparing
      effects have been noted and recovery from anaesthesia is not unduly delayed.
      Hypoxaemia may be problematic. Appropriate monitoring should be done and oxygen
      supplementation and ventilatory support should be available. A poor correlation
      between SpO2 and SaO2 and ETCO2 and PaCO2 was found.

PMID- 12515296
TI  - The effect of storage conditions on samples for the evaluation of copper status
      in blesbok (Damaliscus pygargus phillipsi).
AB  - Investigaltions to determine the effect of sample storage on the concentration of
      copper in liver tissue and on the activity of erythrocyte superoxide dismutase
      were undertaken in preparation for a study of blesbok (Damaliscus pygargus
      phillipsi) that were suspected to be suffering from copper deficiency. Two liver
      samples were collected from each of 20 culled blesbok in a manner that simulated
      the collection of biopsies from the live animal. These samples were stored either
      in 10% formalin or frozen at -20 degrees C until analysed 4 1/2 months later. The
      effect of different methods of sample storage on superoxide dismutase activity
      was determined. Erythrocytes collected from 3 Jersey cows and 5 culled blesbok
      were washed and divided into 0.5 ml portions, stored at room temperature
      (approximately 20 degrees C), in a refrigerator (4 degrees C), frozen at -20
      degrees C in a freezer, and in liquid nitrogen (-200 degrees C). An analysis of
      superoxide dismutase activity was undertaken using a commercial assay kit at
      intervals of 2-4 days until the levels of activity had fallen significantly. The
      copper concentration in formalin-preserved liver samples was significantly lower
      than that measured in frozen liver tissue apparently as a result of leaching. The
      activity of superoxide dismutase in cattle blood was unchanged for 4 days at room
      temperature but fell appreciably after 2 days at 4 degrees C and -20 degrees C.
      Enzyme activity remained unchanged for 200 days in erythrocytes stored in liquid
      nitrogen. Superoxide dismutase activity levels in healthy blesbok were
      considerably lower than those measured in Jersey cows and remained unaffected for
      up to 6 days in samples stored at 4 degrees C and 20 degrees C. The level of
      activity fell significantly thereafter. Samples stored in liquid nitrogen were
      unchanged after 40 days.

PMID- 12515297
TI  - A comparison of the surgical caseloads of selected companion animal hospitals and
      a veterinary academic hospital in South Africa.
AB  - Educational institutions should be aware of the frequency of surgical procedures
      in private practice, to assist both the student and the lecturer in evaluating
      the relative importance of procedures and to structure training programmes
      accordingly. The surgical caseload for 1 year at a veterinary academic hospital
      and 13 private companion animal hospitals registered with the South African
      Veterinary Council were compared. Surgical records were entered into a
      spreadsheet and sorted according to 96 selected surgical procedures to facilitate
      comparisons. Surgical procedures were in turn grouped according to date, species,
      degree of difficulty and frequency of occurrence. Feline procedures were more
      commonly performed in private hospitals. The academic hospital's caseload was
      dominated by major and advanced procedures while the private hospitals carried
      out more minor procedures. At the private hospitals more general surgery, and
      ear, nose and throat surgery as well as dental procedures were performed, while
      at the academic hospital more ophthalmic, orthopaedic, thoracic and neurosurgical
      procedures were carried out. The most commonly performed procedures at the
      academic hospital differed from those at the private hospitals. No seasonal
      trends were evident.

PMID- 12515298
TI  - Haemonchus spp. in sheep farmed under resource-poor conditions in South Africa-
      effect on haematocrit, conjunctival mucous membrane colour and body condition.
AB  - A longitudinal study was conducted on the differential faecal egg counts,
      haematocrits and body condition scores of sheep belonging to resource-poor
      farmers at Rust de Winter, Gauteng province, and Kraaipan, North West Province,
      South Africa. The animals were scored for level of anaemia using the FAMACHA
      method, an assay for the clinical evaluation of anaemia caused by Haemonchus spp.
      Periods of higher Haemonchus egg counts occurred from October to March for sheep
      at Rust de Winter and from September/October to February or April for sheep at
      Kraaipan. Lower haematocrit values were registered during these periods as was a
      higher incidence of anaemic conjunctival mucous membrane colour scores compared
      to the period April to September. No clear relationship between the faecal egg
      counts and the body condition scores was evident. Although wider application of
      the FAMACHA system in sheep raised by resource-poor farmers should be
      investigated, the present study indicates that this method may certainly prove to
      be a valuable worm control strategy for such livestock owners.

PMID- 12515299
TI  - Canine filariosis caused by Dirofilaria immitis in Mozambique: a small survey
      based on the identification of microfilariae.
AB  - Dirofilaria immitis was diagnosed in 4 of 13 indigenous dogs from the Province of
      Zambezia, Mozambique, by acid phosphatase staining of microfilariae. The finding
      reconfirms the occurrence of the parasite in Mozambique after 3 decades and
      emphasises the need for extensive surveys. Additionally, in 1 of the infected
      dogs, microfilariae of Dipetalonema reconditum were detected, which is the 1st
      record of this parasite in Mozambique.

PMID- 12515300
TI  - Effect of clenbuterol on growth, nitrogen and energy balances and endocrine
      status in food-restricted sheep.
AB  - The aim of this study was to examine the effect of the beta2-adrenoceptor
      clenbuterol on food-restricted sheep. Clenbuterol was administered as a dietary
      admixture (4 mg/ kg diet) to a group of male Serra da Estrela sheep (n = 6). The
      animals were housed individually in metabolic cages and fed for 45 days at 65% of
      estimated requirement for energy maintenance. An untreated group with the same
      energy intake level was included as a control. Changes in body mass, nitrogen and
      energy balances and insulin, insulin-like growth factor (IGF-1), and
      triiodothyronine (T3 ) levels in the experimental animals were monitored. During
      the 4th week of the trial, clenbuterol-treated sheep showed increased mass gains,
      greater energy retention and serum IGF-1 levels and decreased T3 serum
      concentrations. This study showed that clenbuterol may induce a protective effect
      in sheep subjected to periods of food deprivation, based on the body mass and
      digestible energy effects manifested by treated animals.

PMID- 12515301
TI  - The prevalence of Cowdria ruminantium in free-living adult Amblyomma hebraeum
      collected at a communal grazing area and in 2 wildlife reserves in South Africa.
AB  - In order to detect the prevalence of Cowdria ruminantium in the vector tick,
      Amblyomma hebraeum, free-living, unfed adult ticks were collected with the aid of
      pheromone/CO2 traps. Ticks were collected at the Rietgat communal grazing area,
      as well as in the southwestern Kruger National Park and in the Songimvelo Game
      Reserve, all located in heartwater-endemic areas of South Africa. The presence of
      C. ruminantium in these ticks was determined by polymerase chain reaction (PCR)
      analysis. Ticks from the Rietgat communal grazing area were assayed in 2 batches
      and 4.7% of the one and 11.3% of the other were positive for infection, while
      5.7% of the ticks collected in the Kruger National Park and 25% in the Songimvelo
      Game Reserve were positive. These results support the contention that a vector
      wildlife cycle of transmission of C. ruminantium, the cause of heartwater in
      domestic ruminants, can be maintained in the absence of the latter animals.

PMID- 12515302
TI  - Suspected primary immune deficiency in a Donge de Bordeaux dog.
AB  - A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic
      responsive gastrointestinal and respiratory disease. Further evaluation showed
      bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential
      cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the
      presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers.
      As the dog came from a narrow genetic base, with related dogs showing similar
      clinical signs, possible B-cell congenital immune deficiency was suspected.

PMID- 12515303
TI  - Host preference of the sheep scab mite, Psoroptes ovis.
AB  - Sheep scab mites, Psoroptes ovis, collected from a Merino donor sheep, were used
      to infest Merino and Dorper sheep, and Angora and Boer goats. Mites were placed
      on the sheep on 1 or 2 occasions and on 5 occasions on the goats. All the animals
      were examined at regular intervals for the presence of scab lesions and living
      mites. Both sheep breeds developed lesions, but those on the Merino sheep were
      always larger than those on the Dorper sheep at the same intervals after
      infestation. None of the goats developed lesions or showed signs of irritation,
      or harboured any mites.

PMID- 12515304
TI  - The rate of spread of sheep scab within small groups of Merino and Dorper sheep.
AB  - A single Merino sheep, artificially infested with the sheep scab mite, Psoroptes
      ovis, and a similarly infested Dorper sheep were placed with 9 uninfested Merino
      or 9 uninfested Dorper sheep respectively during winter and the rate of spread of
      infestation on the uninfested sheep observed. The same procedure was repeated in
      summer. It took 14 and 8 weeks respectively in winter before all sheep in the 2
      groups displayed lesions of sheep scab, whereas in summer it took 10 and 12 weeks
      before all sheep had lesions.

PMID- 12515305
TI  - A case of anaemia in a neonatal warthog (Phacochoerus aethiopicus) and evaluation
      of serum-soluble iron in warthogs.
AB  - A 38-day-old male warthog (Phacochoerus aethiopicus) with marked anaemia
      (haematocrit = 14 %) presented to the Denver Zoological Gardens hospital with
      ataxia, tachypnoea, suspected stunted growth and cardiomegaly. The piglet
      demonstrated some features consistent with both iron deficiency anaemia and
      autoimmune haemolytic anaemia. Serum-soluble iron was below the level of
      detection (< 8.96 micromol/l). Iron deficiency anaemia is a well recognised
      entity in domestic swine reared on concrete and denied access to soil. Fifteen
      captive warthogs were subsequently evaluated for serum soluble iron content (mean
      = 21.62 +/- 4.36 micromol/l as well as 5 neonatal warthog piglets that required
      hand-rearing. Only 1 of 5 neonatal warthog piglets had measurable serum soluble
      iron (9.50 micromol/l). These data suggest that warthogs are similar to domestic
      swine and are born with low iron stores. Some form of iron supplementation should
      be considered for captive neonatal warthog piglets, especially if they are reared
      on concrete.

PMID- 12515306
TI  - Cytoskeleton of human mononuclear cells as a possible peripheral marker for
      phenylalanine neurotoxicity in PKU.
AB  - In this work we tested human mononuclear cells as a peripheral marker to study
      neurotoxicity of phenylalanine (Phe). Slices of cerebral cortex of rats or human
      mononuclear cells were incubated with different concentrations of Phe and/or Ala
      in the presence of 32P-orthophosphate, the cytoskeletal fraction was extracted,
      and the radioactivity incorporated into intermediate filament proteins was
      measured. Our results show that 2 mM Phe as well as 1 mM Ala are effective in
      increasing the 32P in vitro incorporation into IFs in both tissues. When cerebral
      cortex slices or mononuclear cells were incubated with different concentrations
      of Phe and/or Ala, the effects on the 32P in vitro incorporation into IF proteins
      was compatible with an antagonistic mechanism of action of the two amino acids on
      the enzymes of the phosphorylating system. In addition, these blood cells may be
      a possible peripheral marker to study neurotoxicity of Phe in patients with PKU.

PMID- 12515307
TI  - Coenzyme A and short-chain acyl-CoA species in control and ischemic rat brain.
AB  - A rapid and reliable method was developed to quantify brain concentrations of
      coenzyme A (CoA) and short-chain acyl-CoAs having chain length < or = 4 carbon
      atoms. The method employs tissue extraction and isolation using an
      oligonucleotide purification cartridge and quantifies concentrations by peak area
      analysis following high-performance liquid chromatography (HPLC). In adult
      anesthetized rats subjected to 4-s high-energy microwave irradiation to stop
      brain metabolism, the brain concentrations of CoA, 3-hydroxy-3-methylglutaryl-CoA
      (HMG-CoA), acetyl-CoA, and butyryl-CoA equaled 68.7 +/- 18.5, 2.7 +/- 1.5, 7.6 +/
      2.3, and 30.6 +/- 15.9 nmol x g(-1), respectively. After 5 min of complete
      ischemia, the brain concentrations of CoA and HMG-CoA increased 2- and 12-fold
      compared to controls, whereas acetyl-CoA and butyryl-CoA concentrations did not
      change. Markedly elevated levels of CoA and HMG-CoA following cerebral ischemia
      may reflect disturbed energy metabolism and altered formation of cholesterol and
      isoprenoids.

PMID- 12515308
TI  - Glucose and lactate utilization by the amygdala of male and female rats.
AB  - Gonadal hormones appear to modulate brain energy metabolism, and morphological
      and functional sexual differences are found in the amygdaloid complex (AC) of
      rats. Our aim was to study the CO2 production and lipid synthesis, measured by
      the rate of L-[U-14C]lactate or D-[U-14C]glucose utilization (in pmol x hr(-1) x
      mg(-1)), by AC slices in vitro of male and female rats. Lactate was more used
      than glucose as energy substrate (p < 0.01) but no sex-related difference was
      observed in glucose or lactate oxidation to CO2 (p > 0.05) or on lipid synthesis
      obtained from both substrates (p > 0.05). In addition, there was no effect of the
      estrous cycle on lactate oxidation to CO2 by the AC of females (p > 0.05). Based
      on the present data, it appears that the endogenous normal levels of gonadal
      hormones are not able to promote sex-related differences in the in vitro glucose
      or lactate utilization by the AC of rats.

PMID- 12515309
TI  - Whole blood samples from Alzheimer patients and control donors demonstrate
      fluorimetric differences.
AB  - Beta-amyloid peptide plays a crucial role in the pathology of Alzheimer's
      disease. As part of our ongoing fluorimetric studies, in the present report we
      demonstrate differences in resting intracellular free calcium levels of cells in
      the blood derived from sporadic Alzheimer patients and from age-matched control
      individuals. Calcium levels were measured in Fura-2AM-loaded human blood samples
      by dual-wavelength spectrofluorimetry. The resting calcium concentrations of
      blood samples from Alzheimer patients were lower compared to that of the control
      samples. Exposure of control blood samples to beta-amyloid caused an increase in
      the calcium level. Specimens from Alzheimer donors, however, appeared to be
      resistant to the peptide. This simple finding may serve as a springboard to
      monitoring Alzheimer pathology in the peripheral systems of the body.

PMID- 12515310
TI  - Reduction of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to
      chemically induced hyperhomocysteinemia.
AB  - Hyperhomocysteinemia occurs in homocystinuria, an inherited metabolic disease
      clinically characterized by thromboembolic episodes and a variable degree of
      neurological dysfunction whose pathophysiology is poorly known. In this study, we
      induced elevated levels of homocysteine (Hcy) in blood (500 microM), comparable
      to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young
      rats by injecting subcutaneously homocysteine (0.3-0.6 micromol/g of body weight)
      twice a day at 8-hr intervals from the 6th to the 28th postpartum day. Controls
      received saline in the same volumes. Na(+),K(+)-ATPase and Mg(2+)-ATPase
      activities were determined in the hippocampus of treated Hcy- and saline-treated
      rats. Chronic administration of Hcy significantly decreased (40%) Na(+),K(+)
      ATPase activity but did not alter Mg(2+)-ATPase activity. Considering that
      Na(+),K(+)-ATPase plays a crucial role in the central nervous system, our results
      suggest that the brain dysfunction found in homocystinuria may be related to the
      reduction of brain Na(+),K(+)-ATPase activity.

PMID- 12515312
TI  - Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons.
AB  - Using whole cell patch-clamp recordings from pyramidal cells acutely dissociated
      from rat hippocampal slices, Ro-15 1788 (flumazenil, FLU) was shown to enhance
      the GABAA-receptor mediated currents evoked by application of gamma-aminobutyric
      acid (GABA) and to antagonize the enhancing effect of the benzodiazepine agonist
      flurazepam (FZP) on the GABAA response. Both FLU and FZP increased the peak and
      the steady-state components of the responses and accelerated the current decay.
      This suggests that both agents act via a common mechanism on GABA transmission.
      It is concluded that FLU possesses high affinity for the binding site, but low
      efficacy on the GABAA-benzodiazepine receptor. This suggests that FLU acts as a
      partial agonist on GABAA receptors.

PMID- 12515311
TI  - Delayed hypothermia prevents decreases in N-acetylaspartate and reduced
      glutathione in the cerebral cortex of the neonatal pig following transient
      hypoxia-ischaemia.
AB  - The effects of normothermia and delayed hypothermia on the levels of N
      acetylaspartate (NAA), reduced glutathione (GSH) and the activities of
      mitochondrial complex I, II-III, IV and citrate synthase were measured in brain
      homogenates obtained from anaesthetized neonatal pigs following transient in vivo
      hypoxia-ischaemia. In the normothermic animals there was a significant decrease
      in complex I activity and in the levels of GSH and NAA when compared to the
      controls. Delayed hypothermia preserved NAA and GSH at control levels and
      enhanced the rate of complex II-III activity. There was correlation (R = 0.79)
      between GSH and NAA levels when data from all three experimental groups were
      analyzed. Citrate synthase activity was not significantly different in the three
      groups, indicating maintenance of mitochondrial integrity. These data suggest
      that delayed hypothermia affords protection of integrated mitochondrial function
      in the neonatal brain following transient hypoxia-ischaemia.

PMID- 12515313
TI  - Activation of phospholipases A2 and D of a human neuroblastoma cell line (LA-N-2)
      by N-dodecyl-L-lysine amide (compound 24), a putative G protein activator:
      characteristics of inhibition by (-)-nicotine.
AB  - Compound 24, an alkyl-substituted amino acid amide, previously found to activate
      pertussis toxin-sensitive G proteins in cell membranes and membrane protein
      fractions, was used as a tool to determine the mechanism/location of nicotine
      inhibition of amyloid beta peptide-stimulated phospholipase A2 and D activities
      in a human neuroblastoma cell line, LA-N-2, in vitro. In contrast to our previous
      findings with amyloid beta peptide, these phospholipase activations by compound
      24 were not inhibited by (-)-nicotine, cholera toxin or tetanus toxin
      pretreatment. The contrasting activation of these phospholipases by amyloid beta
      peptide and compound 24 are discussed.

PMID- 12515314
TI  - Effect of exogenous melatonin on ethanol-induced changes in Na(+),K(+)- and
      Ca(2+)-ATPase activities in rat synaptosomes.
AB  - In the present study, the effects of acute ethanol (EtOH) toxicity and of
      exogenous melatonin (MLT) on this toxicity were examined by measuring membrane
      bound ATPases and acetylcholinesterase activities in rat synaptosomal membranes.
      The concentrations of plasma alpha-tocopherol and adrenal ascorbic acid (AA) were
      also measured. Synaptosomal Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were
      significantly depressed in acute EtOH-intoxicated rats compared with controls,
      while acetylcholinesterase activity remained unaltered. Pretreatment with MLT (10
      mg/kg) prior to acute EtOH administration prevented EtOH-induced inhibition of
      ATPases. Adrenal AA and plasma alpha-tocopherol levels were also depressed
      regardless of MLT pretreatment. MLT treatment alone affected neither membrane
      bound enzyme activities nor tissue and blood levels of vitamins C and E. It is
      concluded that acute EtOH intoxication disturbs neural transport functions
      through the membrane-bound ATPase activity depression. Reduced AA and alpha
      tocopherol levels may contribute to the neurodegenerative effects of EtOH.
      However, pretreatment with a high dose of MLT before EtOH administration may be
      beneficial to prevent EtOH-induced toxicity on ATPase-mediated neural transport
      functions.

PMID- 12515315
TI  - Effect of hemorrhagic shock on apoptosis and energy-dependent efflux system in
      the brain.
AB  - Recent findings suggest that apoptosis, which contributes to neuronal damage
      after ischemic injury, may play a role in sequelae associated with severe blood
      loss. This study examined the effect of hemorrhage and resuscitation on the
      expression (in situ hybridization and computerized image analysis) of bcl-2 mRNA,
      which codes for a protein that inhibits apoptosis, and mdr1 mRNA, which codes for
      a glycoprotein marker for drug efflux from the brain. Anaesthetized rats were
      subjected to volume-controlled (15 mL/kg) hemorrhage followed by resuscitation
      with shed blood (BR) or nonresuscitated (NR); control animals had femoral artery
      cannulation only (SHAM). Following 24 hr blood loss, distinctly lower levels of
      bcl-2 gene expression were observed in dentate gyrus of NR rats (0.25 +/- 0.04)
      as compared to SHAM rats (0.52 +/- 0.07); suscitation with shed blood prevented
      this reduction (0.58 +/- 0.05). Similar results were observed in cortex,
      striatum, and hypothalamus. Also, mdr1 mRNA levels were significantly reduced in
      all brain areas of the NR group as compared to the BR and SHAM groups. The
      findings suggest that blood resuscitation suppressed apoptosis and protected
      against loss of energy-dependent efflux system in the brain in response to
      hemorrhage.

PMID- 12515316
TI  - Inhibition of creatine kinase activity in vitro by ethylmalonic acid in cerebral
      cortex of young rats.
AB  - Short-chain acyl-CoA dehydrogenase deficiency is an inherited metabolic disorder
      biochemically characterized by tissue accumulation of ethylmalonic (EMA) and
      methylsuccinic (MSA) acids and clinically by severe neurological symptoms. In the
      present study we investigated the in vitro effects of EMA and MSA on the activity
      of creatine kinase (CK) in homogenates from cerebral cortex, skeletal and cardiac
      muscle of rats. EMA significantly inhibited CK activity from cerebral cortex, but
      did not affect this activity in skeletal and cardiac muscle. Furthermore, MSA had
      no effect on this enzyme in all tested tissues. Glutathione (GSH), ascorbic acid
      and alpha-tocopherol, and the nitric oxide synthase inhibitor L-NAME, did not
      affect the enzyme activity per se, but GSH fully prevented the inhibitory effect
      of EMA when co-incubated with EMA. In contrast, alpha-tocopherol, ascorbic acid
      and L-NAME did not influence the inhibitory effect of the acid. The data suggest
      that inhibition of brain CK activity by EMA is possibly mediated by oxidation of
      essential groups of the enzyme, which are protected by the potent intracellular,
      endogenous, naturally occurring antioxidant GSH.

PMID- 12515317
TI  - Energy consumption by phospholipid metabolism in mammalian brain.
AB  - Until recently, brain phospholipid metabolism was thought to consume only 2% of
      the ATP consumed by the mammalian brain as a whole. In this paper, however, we
      calculate that 1.4% of total brain ATP consumption is consumed for the de novo
      synthesis of ether phospholipids and that another 5% is allocated to the
      phosphatidylinositide cycle. When added to previous estimates that fatty acid
      recycling within brain phospholipids and maintenance of membrane lipid
      asymmetries of acidic phospholipids consume, respectively, 5% and 8% of net brain
      ATP consumption, it appears that phospholipid metabolism can consume up to 20% of
      net brain ATP consumption. This new estimate is consistent with recent evidence
      that phospholipids actively participate in brain signaling and membrane
      remodeling, among other processes.

PMID- 12515318
TI  - Activation of BDNF mRNA and protein after seizures in hyperbaric oxygen:
      implications for sensitization to seizures in re-exposures.
AB  - Previous studies have demonstrated that exposure to convulsive doses of
      hyperbaric oxygen (HBO) increases sensitivity to seizures in re-exposures.
      Because brain derived neurotrophic factor (BDNF) is induced after a variety of
      seizures and increases cell excitability, it may contribute to the mechanism of
      sensitization. In this study, a fast induction in BDNF mRNA 2 hr after seizures
      and a temporary increase in BDNF protein 1 day after seizures induced by 100% O2
      at 5 atm (gauge pressure) were demonstrated in the rat cortex. To determine
      whether an elevation in BDNF protein level can modify sensitivity to the toxic
      effect of HBO, recombinant BDNF (12 microg) was injected into cerebral ventricles
      30 min prior to exposure. Administration of exogenous BDNF significantly
      shortened latent time to seizures in HBO exposures. We propose that upregulation
      of BDNF expression in the brain after seizures may contribute to sensitization to
      HBO toxicity.

PMID- 12515319
TI  - Immunosuppressant FK506 induces neurite outgrowth in PC12 mutant cells with
      impaired NGF-promoted neuritogenesis via a novel MAP kinase signaling pathway.
AB  - We obtained a drug-hypersensitive PC12 mutant cell (PC12m3), in which neurite
      outgrowth was strongly stimulated by various drugs such as FK506, calcimycin and
      cAMP, under the condition of NGF treatment. The frequency of neurite outgrowth
      stimulated by FK506 was approximately 40 times greater than by NGF alone. The
      effects of FK506 on neurite outgrowth in PC12m3 cells were inhibited by
      rapamycin, an FK506 antagonist, and by calcimycin, a calcium ionophore. PC12m3
      cells had a strong NGF-induced MAP kinase activity, the same as PC12 parental
      cells. However, FK506-induced MAP kinase activity was detected only in PC12m3
      cells. The activation of MAP kinase by FK506 in PC12m3 cells was markedly
      inhibited by rapamicin and calcimycin. FK506-induced MAP kinase activity was also
      inhibited by MAP kinase inhibitor U0126. These results demonstrate that drug
      hypersensitive PC12m3 cells have a novel FK506-induced MAP kinase pathway for
      neuritogenesis.

PMID- 12515320
TI  - Changes of ATP and ADP in cultured astrocytes under and after in vitro ischemia.
AB  - A very large body of evidence from in vivo studies has been accumulated on a link
      between the change of energy and cell survival/apoptosis. Using an in vitro
      ischemia model, we have previously shown that ischemia could induce apoptosis in
      astrocytes. In this study, we utilized the same in vitro model to investigate
      changes in ATP and ADP levels in cultured astrocytes and attempted to demonstrate
      an energy-cell death linkage. Astrocytes remained unaltered after 2 hr of
      ischemia but were moderately or severely damaged after 4 or 6-8 hr, respectively.
      The astrocytes that survived various lengths of in vitro ischemic incubation
      retained their ability to produce ATP after ischemia. Both ATP and ADP levels
      were increased in astrocytes that remained alive under in vitro ischemia for over
      6 hr. The largest decline in the percent of viable astrocytes during ischemia
      corresponded well to the reduction in ATP and ADP levels in these cultures.

PMID- 12515321
TI  - Effect of 2-fluoropalmitate, cerulenin and tunicamycin on the palmitoylation and
      intracellular translocation of myelin proteolipid protein.
AB  - We have investigated the effect of documented protein palmitoylation inhibitors
      on the fatty acylation and intracellular transport of myelin proteolipid protein
      (PLP). To this end, brain slices from 20-day-old rats were incubated with either
      [3H]palmitate or [3H]leucine in the presence or absence of various concentrations
      of 2-fluoropalmitate (FP), cerulenin (CER), or tunicamycin (TM). FP (> or = 10
      microM) decreased the cellular uptake of [3H]palmitate and consequently reduced
      the labeling of palmitoyl-CoA, glycerolipids and PLP. CER (> or = 1 mM) reduced
      the palmitoylation of PLP with a concomitant decline in protein thiols.
      Consistent with being a fatty acyl-CoA analogue, TM (> or = 200 microM)
      diminished the palmitoylation of PLP and lipids while increasing the amount of
      [3H]palmitoyl-CoA. Although both CER and TM decreased protein palmitoylation,
      only the latter affected the appearance of newly synthesized PLP into myelin.
      Because TM, but not CER, also reduced the formation of lipids, it is concluded
      that palmitoylation is not required for intracellular transport. Finally,
      comparison of the effect of TM in brain slices and in a cell-free system suggests
      that palmitoylation of PLP in whole cells may be an enzymatic process.

PMID- 12515322
TI  - 17beta-estradiol effect on the extracellular concentration of amino acids in the
      glutamate excitotoxicity model in the rat.
AB  - Estrogen has demonstrated a neuroprotective role in a rat model of glutamate
      excitotoxicity and other neurodegenerative disorders. We studied the effect of
      17beta-estradiol on glutamate-induced increases in amino acids levels (aspartate,
      histidine, taurine and GABA) in the rat cortex. Local perfusion of glutamate
      produced a transient increase of aspartate, histidine, taurine and GABA in the
      extracellular fluid. Pretreatment with 17beta-estradiol significantly reduced the
      increases of taurine and moderately attenuated that of histidine, whereas
      aspartate and GABA releases were not modified. The effect of 17beta-estradiol on
      histidine release was reversed by the antiestrogen tamoxifen, suggesting a
      receptor-dependent mechanism. Good correlations between the volumes of the
      glutamate-induced lesions and the extracellular concentrations of taurine and
      aspartate were observed. These findings suggest that the attenuation of the
      glutamate-induced release of taurine by 17beta-estradiol may participate in the
      neuroprotective effects of 17beta-estradiol and that increased levels of
      aspartate and taurine are markers for the severity of the glutamate-induced
      cortical lesions.

PMID- 12515323
TI  - Inhibition of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to
      acute administration of homocysteine is prevented by vitamins E and C treatment.
AB  - In the present study we evaluated the effect of acute homocysteine (Hcy)
      administration on Na(+),K(+)-ATPase activity, as well as on some parameters of
      oxidative stress such as total radical-trapping antioxidant potential (TRAP) and
      on activities of antioxidant enzymes catalase (CAT), superoxide dismutase and
      glutathione peroxidase in rat hippocampus. Results showed that Hcy significantly
      decreased TRAP, Na(+),K(+)-ATPase and CAT activities, without affecting the
      activities of superoxide dismutase and glutathione peroxidase. We also verified
      the effect of chronic pretreatment with vitamins E and C on the reduction of
      TRAP, Na(+),K(+)-ATPase and CAT activities caused by Hcy. Vitamins E and C per se
      did not alter these parameters, but prevented the reduction of TRAP, Na(+),K(+)
      ATPase and CAT activities caused by Hcy. Our results indicate that oxidative
      stress is probably involved in the pathogenesis of homocystinuria and that
      reduction of Na(+),K(+)-ATPase activity may be related to the neuronal
      dysfunction found in homocystinuric patients.

PMID- 12515324
TI  - Effect of propionic and methylmalonic acids on the high molecular weight
      neurofilament subunit (NF-H) in rat cerebral cortex.
AB  - Propionic and methylmalonic acidemias are inherited neurometabolic disorders
      biochemically characterized by tissue accumulation of propionic (PA) and
      methylmalonic (MMA) acids, respectively. Neurofilaments (NF) are important
      cytoskeletal proteins and phosphorylation/dephosphorylation of NF is important to
      stabilize the cytoskeleton. We investigated the effects of PA and MMA on the high
      molecular weight neurofilament subunit associated with the cytoskeletal fraction
      of rat cerebral cortex along development. Cortical slices from 9- to 60-day-old
      rats were incubated with 2.5 mM PA or MMA. The cytoskeletal fraction was
      extracted and the immunoreactivity for phosphorylated or total NF-H was analyzed
      by immunoblotting using specific antibodies. Results showed that treatment of
      tissue slices with the acids induced an increased Triton-insoluble phosphorylated
      NF-H immunoreactivity in up to 17-day-old rats. Furthermore, treatments
      significantly increased the total amount of NF-H in 12-day-old rats. These
      findings indicate that PA and MMA alter the dynamic regulation of NF-H assembly
      in the cytoskeletal fraction.

PMID- 12515325
TI  - Tyrosine kinase activity of nerve growth factor and estrogen in embryonic septal
      neurons cultured from the rat.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by
      dementia, senile plaques, fibrillary tangles, and a reduction of cholinergic
      neurons in the septal nucleus of the brain. Nerve growth factor (NGF) and
      estrogen were studied to observe effects on tyrosine kinase activity in septal
      neurons. The time course of tyrosine kinase activation and number of cells in
      which tyrosine kinase was activated were measured. Tissue from embryonic day 16
      rats was microdissected and the septal neurons obtained were treated with
      estrogen (10 microM) or NGF (100 ng/mL) at intervals of 1, 2, 3, 4, 5, or 10 min.
      Immunostaining for phosphotyrosine revealed that cells treated with NGF showed an
      increase in phosphotyrosine activity within 2-4 min followed by a decline to
      control levels of enzyme activity. Treatment with estrogen led to an increase in
      phosphotyrosine immunostaining within 2-3 min followed by a decline to control
      levels. This time course suggests a mechanism for estrogen activity other than
      the traditional method involving binding to nuclear receptors followed by protein
      synthesis.

PMID- 12515326
TI  - Pertussis toxin-sensitive G proteins mediate the inhibition of basal
      phosphoinositide metabolism caused by adenosine A1 receptors in rat hippocampal
      slices.
AB  - The adenosine A1 receptor selective agonist, N6-cyclopentyladenosine (CPA, 300
      nM) inhibited basal accumulation of [3H]inositol phosphates ([3H]InsPs), but not
      the total levels of membrane [3H]-phosphoinositides, in rat hippocampal slices.
      This action of CPA was not significantly modified when synaptic transmission was
      blocked with tetrodotoxin (TTX, 200 nM) but was prevented in slices pre-incubated
      with pertussis toxin (PTX, 5 microg/mL) for 12-16 hr. Neither PTX nor TTX, when
      applied in the absence of CPA, influenced basal [3H]InsPs accumulation. It is
      concluded that the inhibition of the basal phosphatidylinositol metabolism by
      adenosine A1 receptor activation is independent of neurotransmission and involves
      a PTX-sensitive G protein, probably of the Gi/Go family.

PMID- 12515327
TI  - Participation of the cholinergic system in the excessive grooming behavior
      induced by neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI).
AB  - The neuropeptide (N) glutamic acid (E) isoleucine (I) amide (NEI) injected into
      the ventral tegmental area (VTA) or intraventricularly (icv) induces excessive
      grooming behavior (EGB) and motor activity (MA). Here, we studied whether the
      cholinergic system is involved in the NEI-induced behavior. The present results
      demonstrate that atropine, a general muscarinic antagonist, injected icv previous
      to NEI, suppresses the behavior provoked by icv injections of the peptide,
      whereas the prior icv injection of dyhidro-beta-erythroidine, a general nicotinic
      antagonist, did not affect the EGB and MA induced by the peptide. From the
      experimental evidence, it is suggested that NEI may act specifically on a
      cholinergic afferent to dopaminergic cells. Also, the results appear to indicate
      that a neural target, different from the dopamine system, may be activated by the
      peptide to elicit behavioral changes, such as EGB.

PMID- 12515328
TI  - Allosteric regulation of mouse brain serine racemase.
AB  - Serine racemase, purified from mouse brain, consisted of two isoforms. They had
      similar enzymatic properties and had molecular weights of about 55 kDa based on
      size exclusion chromatography. This is about twice that reported from its
      electrophoretic mobility on SDS gels or from the amino acid sequence of the
      recombinant enzyme. In addition to the previously reported requirements for
      pyridoxal phosphate and reducing agents, we found that both forms of the enzyme
      required Mg2+ and were strongly stimulated by yeast extract. The yeast extract
      could be replaced by ATP, GTP, or ADP and, to a lesser extent, by other
      nucleotides. In the presence of 1 mM ATP, the Km for L-serine decreased from 13
      mM to 1.8 mM with little change in Vmax, indicating an allosteric mechanism for
      nucleotide activation. In addition to acting as a serine racemase, the enzyme has
      been reported to act on L-serine O-sulfate as a dehydratase. When measured by
      HPLC, after derivatization with 2,4 dinitrophenylhydrazine, we found, as
      expected, a very rapid formation of pyruvate from this substrate. L-serine was
      also converted to pyruvate at about twice the racemization rate. L-serine O
      sulfate dehydration was inhibited by ATP, while L-serine dehydration, like
      racemization, was activated by nucleotides, indicating that, for L-serine,
      dehydration and racemization take place at the same site.

PMID- 12515329
TI  - Quality improvement in the developing world.

PMID- 12515330
TI  - Quality assessment of the antenatal program for anaemia in rural Tanzania.
AB  - OBJECTIVE: To assess the quality of antenatal care with respect to anaemia, a
      common health problem, in a developing country. DESIGN: Cross-sectional study.
      SETTING: Rufiji rural district, coastal Tanzania. STUDY PARTICIPANTS: Three
      hundred and seventy-nine consecutively enrolled pregnant women from 16 randomly
      selected antenatal clinics, including 10 dispensaries, four rural health centres
      and two hospitals. METHODS: We noted availability of infrastructure for
      management of anaemia, observed provider-client interaction, and interviewed
      women who attended antenatal clinics. An observer and health workers measured
      haemoglobin levels and their measurements were compared. MAIN OUTCOME MEASURES:
      Quality of antenatal care, anaemia in pregnancy, and maternal satisfaction.
      RESULTS: Half of the rural health clinics had no instrument to measure
      haemoglobin. The majority (58%) of pregnant women were not checked for anaemia at
      all, 10% were clinically examined, and 37% had haemoglobin assessed. The
      agreement between health workers' (using Tallqvist) and the observers' (using
      HemoCue) measurements of haemoglobin was poor to fair. The prevalence of anaemia
      (Hb < 10.5 g/dl) and severe anaemia (< 7.0 g/dl) was 58% and 6.2%, respectively,
      but overall only 4% of the anaemic pregnant women had specific action taken
      within the antenatal care program. CONCLUSION: Deficiencies in quality of
      screening, diagnostic information, and individual counselling need to be
      addressed before any impact of the antenatal care programme on anaemia can be
      expected.

PMID- 12515331
TI  - Quality assurance in follow-up and initial treatment for screening mammography
      programs in 22 countries.
AB  - OBJECTIVE: To describe the quality assurance activities related to follow-up
      evaluation of abnormal screening mammograms and subsequent initial treatment of
      women determined to have breast cancer for the screening programs represented in
      the International Breast Cancer Screening Network (IBSN). DESIGN: Analysis of
      data from a survey that included questions about screening program policies,
      standards, and procedures for follow-up of women with abnormal mammograms, as
      well as the data and measures that programs use to assess the adequacy of follow
      up and initial treatment. SETTING AND PARTICIPANTS: IBSN representatives in 23
      countries completed a comprehensive questionnaire between May and December 1998.
      RESULTS: Two-thirds of IBSN countries reported that they have a written policy or
      guidelines for follow-up of an abnormal mammogram; 64% require accreditation of
      the cytology or pathology laboratories that analyze breast specimens, or subject
      pathology laboratories to external audits. Of the 22 activities and measures
      related to quality of follow-up and initial treatment that we examined, all
      countries had in place at least half of them, although countries were more likely
      to have implemented activities and measures related to data collection and
      evaluation than to processes of care. CONCLUSIONS: Population-based screening
      mammography programs cannot achieve the goal of reducing breast cancer mortality
      if women with abnormal mammograms do not receive appropriate, timely follow-up
      and initial treatment. This study shows that IBSN countries vary in their
      implementation of procedures and measures to assure the quality of follow-up and
      initial treatment for women with abnormal screening mammograms. There is more
      emphasis on collecting and evaluating data than establishing mechanisms to ensure
      that the processes of care for follow-up and initial treatment are of high
      quality.

PMID- 12515332
TI  - The Victorian emergency department collaboration.
AB  - OBJECTIVES: The aim of the project was to bring together 17 major emergency
      departments across Victoria, Australia, and the Australian Capital Territory to
      work together over an 8-month period to reduce both clinical and operational
      waits and delays, and to improve patient satisfaction. DESIGN: The collaborative
      was based on the Institute for Healthcare Improvement's Breakthrough Series, and
      utlilized their intellectual property and methodology adapted for the Australian
      setting. SETTING: The largest (by annual attendances) 17 emergency departments in
      the State of Victoria and one hospital in the Australian Capital Territory
      participated. STUDY PARTICIPANTS: Each hospital sent a team of three to five
      persons, which included the Emergency Department Medical Director and Nurse in
      Charge, and an Executive Sponsor to each learning session. INTERVENTIONS: The
      teams were required to attend four learning sessions, to participate during the
      action period in both clinical and operational improvement activities, and to
      report regularly in the form of data reports and conference calls. MAIN OUTCOME
      MEASURES: Each team selected at least one or two clinical topics for improvement
      and at least one operational project to undertake during the life of the
      collaborative. A patient satisfaction survey was commenced towards the end of the
      project. RESULTS: Forty-seven clinical projects were nominated during the life of
      the collaborative and 32 of these were completed, with 31 resulting in
      significant improvement or achieving target. Thirty-nine operational projects
      were nominated, 30 of which were completed, with 24 of these achieving
      improvement or target. Numerous additional achievements occurred, which evolved
      from the framework of supported collaboration. CONCLUSION: The spread of
      knowledge and innovation can be best facilitated rapidly by teams working
      together using a structured program in a supported environment.

PMID- 12515333
TI  - Reliability and validity of the Satisfaction with Hospital Care Questionnaire.
AB  - OBJECTIVE: To establish the psychometric properties of the Satisfaction with
      Hospital Care Questionnaire (SHCQ) for measuring patient satisfaction and
      evaluations of hospital care quality. DESIGN AND PARTICIPANTS: Patients (n = 275)
      and staff members (n = 83) of four hospital wards completed the 57-item SHCQ
      addressing 13 aspects of care. Staff members completed the SHCQ from the
      patient's perspective. The data were analyzed within the framework of
      generalizability theory. MAIN OUTCOME MEASURES: Generalizability coefficients
      (GCs) and standard errors of measurement (SEs). RESULTS: GCs indicating
      differentiation among patients with different overall levels of satisfaction
      (SHCQ mean scores) were high (> 0.90). GCs indicating differentiation among
      patients as to satisfaction with aspects of care (SHCQ scale scores) were
      generally satisfactory (> 0.75) to high. Patients agreed well on overall level of
      hospital care quality (GCs > 0.90) and differentiated reliably (GCs > 0.80) among
      aspects of care. No differentiation among wards was found with respect to quality
      of care. Patients and staff agreed to a considerable extent (0.78) on ranking the
      SHCQ items on care quality, but staff ratings were lower. Reliability and
      validity of patients' evaluations of quality of hospital care varied according to
      aspect of care. CONCLUSIONS: The SHCQ reliably establishes both patient
      satisfaction and overall quality of hospital care. Whereas patients' ratings may
      be too lenient, their ranking of the items on care quality appears to be valid,
      and is therefore suitable for monitoring and improving hospital care. Within
      scales, however, results should be interpreted more cautiously: for some items,
      patients cannot really tell the difference in quality of care.

PMID- 12515334
TI  - Metric properties of the appropriateness evaluation protocol and predictors of
      inappropriate hospital use in Germany: an approach using longitudinal patient
      data.
AB  - BACKGROUND: The German health care system, renowned for its unrestricted access,
      high quality care, and comprehensive coverage, is challenged by increasing health
      care costs. This has been attributed partly to inefficiencies in the in-patient
      sector, but has been studied little. Attempts at quality improvement need to
      relate costs to outcomes. Until now, there has been no standardized methodology
      to evaluate the appropriateness of hospital care. OBJECTIVE: To develop and
      evaluate the metric properties of a method to assess inappropriate hospital care
      in Germany based on a widely used measure, the Appropriateness Evaluation
      Protocol (AEP). METHODS: The original AEP was translated and adapted to reflect
      differences in the provision of health care in Germany. Psychometric testing was
      performed in a stratified sample of all patients admitted to the Departments of
      Medicine and Surgery of a 400-bed teaching hospital during 1 year. Three board
      certified physicians participated in each department to evaluate intra-rater
      reliability, while two additional independent physicians judged inter-rater
      reliability. RESULTS: Inter-rater agreement for the evaluation of hospital days
      among surgical patients was 84% (80-87%), with an average kappa value of 0.58
      (0.48-0.68). Corresponding figures for patients in medicine were 76% (73-80%)
      with a K value of 0.42 (0.34-0.42). Inter-rater agreement for hospital admissions
      and K was 74% (62-86%) and 0.44 (0.21-0.67) in surgery, and 92% (85-100%) and
      0.31 (0-0.80) in medicine, respectively. Thirty-three per cent of all admissions
      and 28% of consecutive hospital days were judged inappropriate in surgery; among
      medicine patients, reviewers found 6% of admissions and 33% of hospital days
      inappropriate. Time since admission was the strongest predictor of inappropriate
      hospital use adjusted for length of stay, comorbidity, age, and gender.

PMID- 12515335
TI  - Influence of length of stay on patient satisfaction with hospital care in Japan.
AB  - OBJECTIVE: The objective of this study was to identify specific patient
      satisfaction items related to overall satisfaction by different length of stay
      (LOS) for patients in Japanese hospital settings. METHODS: This cross-sectional
      study involved a participant sample, drawn from 77 voluntarily participating
      hospitals throughout Japan, of in-patients discharged to the community. Older
      patients and psychiatric, pediatric, obstetric and gynecologic patients were
      excluded. The 1050 respondents analyzed (response rate > or = 5l.1%) were divided
      into three groups based on their LOS: group 1, LOS < or = 1 week; group 2, LOS <
      or = 1 month; and group 3, LOS > 1 month. Using stepwise multiple regression
      analysis, we explored for each LOS group the relationship between overall patient
      satisfaction and satisfaction with 33 individual items, including three regarding
      perceived reputation of the hospital in question. RESULTS: Some unique
      satisfaction items for each group (e.g. 'skill of nursing care' in group 1,
      'Recovery of physical health', 'skill of nursing care', and 'respect for patients
      opinions and feelings' in group 2, and 'relief from pain' and 'respect for
      patients' opinions and feelings' in group 3) were significantly associated with
      overall satisfaction. In all three groups, common items (e.g. 'recovery from
      distress and anxiety' and 'doctor's clinical competence') also related
      significantly to overall satisfaction. Two items pertaining to the hospital
      reputation dimension (e.g. 'family member's evaluation of the hospital' and
      'hospital reputation among other patients') were also significant predictors of
      overall satisfaction in all three groups. CONCLUSION: The findings show that
      according to LOS, unique items could determine significantly the achievement of
      overall satisfaction, while some common predictors across all three LOS groupings
      also seemed to be indispensable for inpatient's assessment of hospital care. It
      was also confirmed in this study that a positive perception of hospital
      reputation might have an important role in patient satisfaction in Japan.

PMID- 12515336
TI  - Prophylactic antibiotic prescription for cesarean section.
AB  - OBJECTIVES: To assess the use of prophylactic antibiotics for cesarean section,
      and to identify factors associated with a doctor's intraoperative prescription.
      DESIGN: A hospital-based, cross-sectional study. STUDY PARTICIPANTS: All 967
      medical records of women undergoing cesarean section from January 1998 to
      February 1999 in a university hospital, Southern Thailand. MAIN MEASURES:
      Independent variables consisted of patient and doctor factors. The outcome
      variable was whether any antibiotics were given intraoperatively. Multivariate
      logistic regression with random effects was used to identify factors associated
      with the doctor's prescription. RESULTS: Prophylactic antibiotics were prescribed
      in 82% of all patients. One hundred and eighty-eight patients (21%) received
      antibiotics postoperatively. Of the patients receiving intraoperative antibiotics
      after cord clamping, 8% received only a single dose and 53% received an
      additional postoperative prescription. The most commonly used antibiotic was
      ampicillin. Intraoperative prescription was significantly associated with longer
      duration of ruptured membranes, higher number of vaginal examinations and
      doctors' age. Doctors aged 30-39 years had three and seven times the likelihood
      of prescribing intraoperative antibiotics compared with their younger and older
      colleagues, respectively. CONCLUSIONS: Administration of single-dose
      prescriptions was still an uncommon practice. Prophylaxis was given more commonly
      to patients with well known risks for infection, and was given by doctors aged 30
      39 years.

PMID- 12515337
TI  - Specialists' expectations regarding joint treatment guidelines for primary and
      secondary care.
AB  - OBJECTIVE: To identify factors that may hinder or facilitate specialists' use of
      joint treatment guidelines for primary and secondary care. DESIGN: Qualitative
      study using focus group discussions based on a topic guide with open-ended
      questions. MAIN OUTCOME MEASURES: Themes identified by two researchers that
      specify the specialists' views on the use and implementation of treatment
      guidelines in general, and transmural guidelines in particular. SETTING:
      Departments of Cardiology and Internal Medicine in three Dutch hospitals. STUDY
      PARTICIPANTS: Ten general internists, 11 cardiologists, and six
      gastroenterologists participating in seven group discussions. RESULTS:
      Specialists did not perceive the treatment guidelines as useful for their own
      field of expertise, but expected that joint guidelines might improve integration
      between primary and secondary care. Furthermore, the guidelines could be useful
      for areas outside their expertise, for specialists in training, and for general
      practitioners. Concerns were expressed regarding their content and development
      process. In addition, specialists feared negative consequences, such as loss of
      autonomy, extra administrative workload, and organizational and financial
      barriers such as loss of industry-sponsored research and conferences. CONCLUSION:
      Specialists are not very motivated to use the guidelines themselves. This is a
      major obstacle that should be addressed in an implementation programme.
      Furthermore, negative outcomes at the organizational and financial levels must be
      minimized or compensated for. A joint implementation programme seems worthwhile,
      making use of the advantage seen by specialists in making agreements with general
      practitioners.

PMID- 12515338
TI  - Inadequate monitoring in the absence of a treatment protocol leads to an adverse
      outcome.

PMID- 12515339
TI  - Design effects and intraclass correlation coefficients from a health facility
      cluster survey in Benin.

PMID- 12515340
TI  - Laboratory security and emergency response guidance for laboratories working with
      select agents. Centers for Disease Control and Prevention.
AB  - In recent years, concern has increased regarding use of biologic materials as
      agents of terrorism, but these same agents are often necessary tools in clinical
      and research microbiology laboratories. Traditional biosafety guidelines for
      laboratories have emphasized use of optimal work practices, appropriate
      containment equipment, well-designed facilities, and administrative controls to
      minimize risk of worker injury and to ensure safeguards against laboratory
      contamination. The guidelines discussed in this report were first published in
      1999 (U.S. Department of Health and Human Services/CDC and National Institutes of
      Health. Biosafety in microbiological and biomedical laboratories [BMBL]. Richmond
      JY, McKinney RW, eds. 4th ed. Washington, DC: US Department of Health and Human
      Services, 1999 [Appendix F]). In that report, physical security concerns were
      addressed, and efforts were focused on preventing unauthorized entry to
      laboratory areas and preventing unauthorized removal of dangerous biologic agents
      from the laboratory. Appendix F of BMBL is now being revised to include
      additional information regarding personnel risk assessments, and inventory
      controls. The guidelines contained in this report are intended for laboratories
      working with select agents under biosafety-level 2, 3, or 4 conditions as
      described in Sections II and III of BMBL. These recommendations include
      conducting facility risk assessments and developing comprehensive security plans
      to minimize the probability of misuse of select agents. Risk assessments should
      include systematic, site-specific reviews of 1) physical security; 2) security of
      data and electronic technology systems; 3) employee security; 4) access controls
      to laboratory and animal areas; 5) procedures for agent inventory and
      accountability; 6) shipping/transfer and receiving of select agents; 7)
      unintentional incident and injury policies; 8) emergency response plans; and 9)
      policies that address breaches in security. The security plan should be an
      integral part of daily operations. All employees should be well-trained and
      equipped, and the plan should be reviewed annually, at least.

PMID- 12515341
TI  - Integrating information for better environmental decisions.
AB  - As more is learned about the complex nature and extent of environmental impacts
      from progressive human disturbance, scientists, policy analysts, decision makers,
      educators, and communicators are increasingly joining forces to develop
      strategies for preserving and protecting the environment. The Eco-Informa
      Foundation is an educational scientific organization dedicated to promoting the
      collaborative development and sharing of scientific information. The Foundation
      participated in a recent international conference on environmental informatics
      through a special symposium on integrating information for better environmental
      decisions. Presentations focused on four general themes: (1) remote sensing and
      data interpretation, including through new knowledge management tools; (2) risk
      assessment and communication, including for radioactively contaminated
      facilities, introduced biological hazards, and food safety; (3) community
      involvement in cleanup projects; and (4) environmental education. The general
      context for related issues, methods and applications, and results and
      recommendations from those discussions are highlighted here.

PMID- 12515342
TI  - Halogenated compounds and climate change: future emission levels and reduction
      costs.
AB  - OBJECTIVES: This work assesses the contribution to climate change resulting from
      emissions of the group of halogenated greenhouse gases. METHODS: A bottom-up
      emission model covering 22 technological sectors in four major regions is
      described. Emission estimates for 1996 and projection for 2010 and 2020 are
      presented. The costs for deep cuts into projected emission levels are calculated.
      RESULTS: The substances covered by this study have contributed emissions of 1100
      +/- 800 MT CO2 equivalents per year in 1996. In terms of their relative
      contribution to emissions of CO2 equivalents, this corresponds to 3 +/- 2% of
      global emissions of all anthropogenic greenhouse gases. The wide range of
      uncertainty is due to the poorly quantified net global warming potential of the
      ozone depleting substances, which have an indirect cooling effect on climate
      through the destruction of stratospheric ozone. For annual emissions of HFCs,
      PFCs and SF6 (which are regulated under the Kyoto Protocol and for which global
      warming potentials are well defined), the relative contribution is projected to
      increase to 2% (600 MT CO2 eq.) of global greenhouse gas emissions by 2010. This
      trend is expected to continue, emissions are projected to grow to a contribution
      of roughly 3% (870 MT CO2 eq.) in 2020 compared to 0.9% (300 MT CO2 eq.) in 1996.
      For HFCs, PFCs and SF6, this study identifies global emission reduction
      potentials of 260 MT CO2 eq. per year in 2010 and 640 MT CO2 eq. per year in 2020
      at below US$ 50 per ton. These values correspond to roughly 40% and 75% of
      projected emissions in 2010 and 2020, respectively.

PMID- 12515343
TI  - The southern hemisphere ozone hole split in 2002.
AB  - Among the most important aspects of the atmospheric pollution problem are the
      anthropogenic impacts on the stratospheric ozone layer, the related trends of the
      total ozone content drop and the solar ultraviolet radiation enhancement at the
      Earth's surface level. During September 2002, the ozone hole over the Antarctic
      was much smaller than in the previous six years. It has split into two separate
      holes, due to the appearance of sudden stratospheric warming that has never been
      observed before in the southern hemisphere. The analysis of this unprecedented
      event is attempted, regarding both the meteorological and photochemical aspects,
      in terms of the unusual thermal field patterns and the induced polar vortex
      disturbances.

PMID- 12515344
TI  - Studies on reactions of ozone with alkenes.
AB  - In the last years, a continuous increase of the O3 concentration has been
      recorded in the lower atmospheric layers. Photochemical reactions with NO(x), CO
      and organic compounds are the main sources of O3 in the troposphere. In this
      work, an attempt was made to determine the impact of alkenes on the O3
      concentration in the troposphere. A study on the gas-phase reactions of 03 with 1
      hexene, 1-heptene and 1-nonene was made. The reactions were carried out at room
      temperature under atmospheric pressure. Ozone was formed by the ultraviolet
      radiation emitted by a mercury lamp, in order to simulate the atmospheric
      conditions. The changes with time in the concentration of O3, 1-alkenes and
      formed aldehydes were investigated. Qualitative and quantitative analyses were
      done by means of the gas chromatography and colorimetry. The following products
      were identified: pentanal from 1-hexene; hexanal from 1-heptene; oktanal from 1
      nonene. For each of the reactions, HCHO was also determined as a product. The
      reaction rate constants were calculated and obtained in units of 10(-17) cm(-3)
      molecule(-1) s(-1): 1.94-0.99 for 1-hexene, 5.54-4.51 for 1-heptene and 1.54-0.76
      for 1-nonene. Based on the results obtained, an explanation of O3 concentration
      variations in the planetary boundary layer can be given. Last year a considerable
      increase of O3 concentration on the roads of Western Europe was recorded. This
      increase could have resulted from the decrease of alkene concentration in the air
      due to common use of the catalytic converters in cars. The unsaturated
      hydrocarbons rapidly oxidize on the catalyst. In Eastern Europe, where the amount
      of cars equipped with catalytic converters is smaller than in Western Europe, the
      alkene content in the exhaust fumes results in a decrease of the O3 concentration
      in the troposphere.

PMID- 12515345
TI  - Application of ground-based Lidar for studies of the dynamics of ozone in a
      mountainous basin.
AB  - A ground-based Differential Absorption Lidar was employed to study the dynamics
      of atmospheric O3 within the planetary boundary layer of a basin in the
      'Fichtelgebirge' mountains, NE Bavaria. In particular, the night-time dynamics of
      O3 linked to the ground were investigated. The Lidar system measured vertical
      profiles of O3 up to 1 km above ground. For detailed analysis of the night-time
      dynamics of ozone, supplementary data from three ground-based stations (measuring
      mixing ratios of O3 and NO(x), as well as meteorological parameters) are
      essential. The Lidar results could be evaluated with these data from various
      altitudes above the basin floor. For the station with the largest (vertical)
      distance to the ground-based Lidar, the agreement was very good at all times. The
      Lidar method proved to be useful for examining the spatial distribution of O3.
      The observed night-time decrease of O3 at the bottom of the basin was due to
      deposition and to advection of air masses containing less O3 from the mountain
      slopes.

PMID- 12515346
TI  - The interfacial mass transfer resistances of the ozone dry deposition over the
      field soil of Taichung County in Taiwan.
AB  - This study aims to design a dry deposition chamber and to measure ozone depletion
      over the Taichung field soil. This study seeks to verify the phenomena by an
      experimental and mathematical model. It is demonstrated that interfacial mass
      transfer resistances of ozone dry deposition involve reactive resistance (R(sr))
      and kinetic resistance (R(sk)). It reveals the chemical reaction (O3 + NO -->
      NO2) to produce the reactive resistance, and verifies that the interfacial mass
      transfer resistances depend on nitrogen oxide emission and soil temperature. It
      shows that the interfacial mass transfer resistances are reduced with increasing
      soil temperature (T(S)). The model profiles are smaller than the observed data
      within a relative error of 15%. The reactive resistance decreases exponentially
      with increasing soil temperature; R(sr)(-1) (cm x sec(-1)) = 0.0001 exp
      (0.1455T(S)). The kinetic resistance decreases linearly with increasing soil
      temperature; R(sk)(-1)(cm x sec(-1)) = 0.0108T(S) + 1.4012. This model is more
      accurate with higher soil temperature and larger ozone concentration. Results are
      consistent with thermodynamics and reaction kinetics. Ozone dry deposition over
      agricultural soil causes conversion of nitrogen oxide (NO) to nitrogen dioxide
      (NO2).

PMID- 12515347
TI  - Estimating receptor sensitivity to spatial proximity of emissions sources.
AB  - Spatial proximity of emissions sources to receptors may affect sensitivity to
      potential adverse human health effects. This research investigates whether
      receptor sensitivity to the location of emission sources can be utilized
      efficiently to minimize health risk in selecting sites for industrial
      enterprises, thermal electric stations, etc. A sensitivity function that is
      independent of the location of pre-existing emission sources is derived and
      applied to Minsk, Belarus. The function estimates exposures based on weather and
      climatic conditions as well as the distribution of population density at a given
      locality. Arraying prospective sites based on their sensitivity function
      magnitude provides a technique for minimizing health risk based on receptor
      sensitivity to the spatial proximity of atmospheric emissions sources.

PMID- 12515348
TI  - Atmospheric lead and bromine in Germany: post-abatement levels, variabilities and
      trends.
AB  - INTENTION, GOAL, SCOPE, BACKGROUND: Abatement measures since the 1970s have
      depleted lead and bromine levels in the atmosphere over large parts of Europe.
      Our knowledge of the atmospheric cycling of these elements while a several decade
      long period of intensive mobilization reaches its end is incomplete. OBJECTIVE:
      We have characterized the trends in the atmospheric levels of Pb and Br and
      present-day temporal and spatial variabilities. METHODS: This was achieved by
      short-term (weeks) and long-term (years) measurements of particulate Pb and Br at
      various sites in Germany. Samples of atmospheric particulate matter were
      collected on filter membranes and analyzed by x-ray fluorescence. RESULTS AND
      DISCUSSION: Average Pb levels at rural and urban inland sites did not exceed
      concentrations in background aerosols, sampled at a Baltic Sea coastal site, by
      more than a factor of 3. Due to sea salt, bromide inland particulate Br levels
      are below those at a coastal site. There, non-sea salt Br, however, is
      significant as well. Urban Pb and Br levels are not necessarily higher than rural
      levels. The concentration levels have decreased in such a way that the previously
      common source, local vehicular traffic emissions, is no longer predominant.
      Regional rather than local sources have been increasingly determining the
      concentrations since the 1990s. This is more pronounced for Br than for Pb. We
      found indications for coal burning and long-range transport as significant Pb
      sources. For particulate Pb species, a range of ages (elapsed time since Pb
      emission) has been found. This range shows two maxima corresponding to
      characteristic times of 72 and 24 h. CONCLUSIONS: The (mean) atmospheric
      residence time of particulate Pb is longer than the residence time of Br, in
      particular in the wintertime. The chemical species contributing to atmospheric Pb
      should be addressed in future studies. RECOMMENDATION AND OUTLOOK: Clearly,
      despite effective abatement measures, atmospheric Pb will continue to be
      dominated by anthropogenic mobilization. The influence from long-range transport
      can be expected to decrease with the effectiveness of abatement programmes in
      neighbouring countries of the region.

PMID- 12515349
TI  - Prediction of vapour pressures for halogenated diphenyl ether congeners from
      molecular descriptors.
AB  - BACKGROUND, AIM AND SCOPE: Polychlorinated diphenyl ethers (PCDE) and
      polybrominated diphenyl ethers (PBDE) have both been identified as environmental
      contaminants. The physical properties are important in determining the
      distribution and fate of organic contaminants in the environment. The purpose of
      the present investigation was to characterise halogenated diphenyl ethers using
      computationally derived descriptors, and to develop calibration models for the
      vapour pressure from published experimental data. METHODS: Experimental data for
      vapour pressures were obtained from the literature. The chemical structure of
      each PCDE and PBDE congener was optimised prior to descriptor generation. The
      data analysis was performed using principal component analysis (PCA) and partial
      least squares regression (PLSR). The calibration models were validated with
      external test sets. RESULTS AND DISCUSSION: All congeners of PCDEs and PBDEs were
      characterised by 795 molecular descriptors and two principal components could
      account for about two thirds of the variance within each group. Bilinear
      calibration models were developed that could explain 99.4% of the variance in the
      external validation test sets. Vapour pressures were subsequently predicted for
      all congeners that were adequately described by these calibration models. The
      type and number of halogen atoms in the molecule were the main factors
      influencing the vapour pressures of halogen substituted diphenyl ethers, but the
      variations in substitution pattern was also shown to be a significant factor.
      CONCLUSIONS: The molecular descriptor patterns of halogenated aromatic compounds
      such as diphenyl ethers can be described and interpreted using principal
      component analysis (PCA). The major sources of variation in the descriptor spaces
      for PCDEs and PBDEs are the same as those contributing to the differences in
      vapour pressure, similar to what has previously been reported for the PCBs. The
      bilinear calibration models for vapour pressure presented here, has a standard
      error of prediction that is lower than what is reported as the experimental
      uncertainty or observed as deviations between experimental investigations. The
      estimated prediction errors are expected to be within the reported boundaries
      when the models are applied to new objects within the same molecular descriptor
      space, and model predictions can hence extend the current database of
      experimental values. RECOMMENDATIONS AND OUTLOOK: The results from this
      investigation and others show that the establishment of quantitative structure
      property relationships (QSPR) is a viable approach to estimate physical
      properties for halogenated diphenyl ethers. It is easy to foresee an increased
      need for using QSPR estimation methods in the future, for evaluation of the
      environmental fate for organic pollutants. Despite method developments and
      automation, it is unlikely that laboratory determinations can cope with the pace
      that new pollutants are identified.

PMID- 12515350
TI  - The role of the egg jelly coat in protecting Hyla regilla and Bufo canorus
      embryos from ultraviolet B radiation during development.
AB  - BACKGROUND: Previous studies have suggested that Ultraviolet B (UVB) radiation
      may play a role in amphibian population declines. Some of these studies also
      indicate that egg hatching success is unaltered in some species of anurans as a
      result of UVB exposure. It has been proposed that the egg mass jelly provides
      photoprotection to the developing embryos. METHODS: Direct spectrophotometric
      scans of egg jelly, scans of egg jelly methanol extracts, and experimental
      manipulation in a solar simulator during development were all used to assess the
      role of egg mass jelly as a photoprotective agent. RESULTS/DISCUSSION: For Hyla
      regilla, scans of egg jelly and methanolic extracts (for mycosporine-like amino
      acid content) both displayed no absorption in the UV range. Experimental
      manipulation (removal of egg mass jelly) with both Hyla regilla and Bufo canorus
      egg masses in a solar simulator demonstrated that egg mass jelly played no
      apparent role in photoprotection of either of these species. CONCLUSIONS: Based
      on the results in this study it seems unlikely that the egg jelly coat is playing
      a crucial role in protecting developing embryos from the impact of UVB radiation.

PMID- 12515351
TI  - Effects of heavy metals on the nitrogen metabolism of the aquatic moss Fontinalis
      antipyretica L. ex Hedw. A 15N tracer study.
AB  - The assessment of pollution in aquatic systems necessitates an accurate
      indication of toxicity of heavy metals for organisms and ecosystems. We used the
      stable nitrogen isotope 15N to estimate the influence of the heavy metals Cd, Pb
      and Zn on the synthesis of nitrogen-containing fractions in the aquatic moss
      Fontinalis antipyretica. This method permits conclusions concerning inhibitory
      effects of these heavy metals on the assimilation of nitrogen and the
      biosynthesis of amino acids and proteins. The moss was exposed to metal
      concentrations of 25-500 microM over a period of 5-10 days. 15N abundance of
      exposed plants was compared with that of control plants. Similar to a loss of
      vitality determined using a fluorometric assay, a decrease of the 15N abundance
      in the N fractions of Fontinalis antipyretica was measured in dependence on the
      metal concentration. Nevertheless, the individual inhibition by the distinct
      metals was different, so that the following order of toxicity was derived: Cd >>
      Pb > Zn.

PMID- 12515352
TI  - Use and fate of pesticides in the Amazon State, Brazil: risk to human health and
      the environment.
AB  - During the last 30 years, the increase of the human population in the Amazon
      introduced the need for additional food production and caused the state
      government to implement programs to increase and improve agricultural production.
      The production of nontraditional crops introduced several problems unknown to
      traditional farmers, since they are not well adapted to tropical conditions.
      Their susceptibility to insects, fungi and other plagues, and the competition
      with native vegetation forced farmers to use pesticides intensively. Amazonian
      farmers were not adequately prepared for the use of this new technology; they
      ignored the risk of pesticides to human health and the environment. Using the
      region of the state capital Manaus as an example, the characteristics of the
      pesticide use are described (e.g. the increased use and the lack of personal
      protective equipment, as well as the legal situation). In detail, the
      registration status of pesticides used in the State of Amazonas and the state of
      their registration in the European Union is compared. Finally, it is concluded
      that the use and the fate of pesticides in the Amazon region has to be monitored.
      Data of the effects on humans and on the environment have to be collected from
      the literature or have to be produced in standardized tests, so that an
      environmental risk assessment becomes possible. Training and information programs
      are urgently needed in order to build up environmentally sustainable agriculture.
      Finally, the enforcement of Brazilian laws concerning pesticide registration has
      to be improved.

PMID- 12515353
TI  - Pesticide studies: replicability of micro/mesocosms.
AB  - The objective of this state-of-the-art review was to quantify the replicability
      of pesticide studies using micro/ mesocosms. Low interpretability of
      micro/mesocosm studies, and inconclusive and highly variable data, resulted in a
      discontinuation of the use of these studies for the registration of pesticides.
      Coefficients of variation, CV%, were calculated on the basis of data tables as a
      measure of statistical 'effectiveness' taken from the literature. The average CV
      in the investigated studies was 45%; larger out-door mesocosms averaged 51%, and
      smaller indoor micro/mesocosms averaged 32%. CVs on variables involving animals
      were higher than CVs on plant end-points, which in turn were higher than abiotic
      variables for all experiments. However, to enhance the interpretability and
      implementation of micro/mesocosm studies for pesticide registration, a number of
      context-dependent steps could be incorporated; 1) determine the appropriate
      experimental design and number of replicates by using power analysis, 2) Utilise
      advanced statistical analysis, such as probabilistic effect distribution and
      principal response curves, 4) report, preferably in quantitative terms using
      power analysis, the risk of Type II error. The author's primary conclusion is
      that the level of CVs is context dependent and, therefore, it is not possible to
      suggest a generally acceptable level of CVs for all experiments. This has been
      suggested both directly and indirectly in the literature. Moreover, the number of
      insignificant (p > 0.05) results is high, 88% of all test biotic variables had no
      statistical significance. The average number of replicates were 3-4, which
      theoretically should yield significant effects at least at the highest test
      concentration, then resulting in 75-66% insignificant results.

PMID- 12515354
TI  - Intergovernmental Panel on Climate Change (IPCC): keynote address. 26 August-4
      September 2002. UN World Summit on Sustainable Development in Johannesburg, South
      Africa.

PMID- 12515355
TI  - The Johannesburg Summit and the difficulty with the term 'sustainability'. 26
      August-4 September 2002.

PMID- 12515356
TI  - Stationary phases for thin-layer chromatography.
AB  - This paper presents a review of the literature concerning development of the
      stationary phases for thin-layer chromatography (TLC) in the last ten years. The
      silica gel remains the most important adsorbent for TLC separation. The kinetic
      properties of the silica-gel thin layer and the new TLC plates have been
      presented. Other materials used as stationary phase were alumina, zirconium
      oxide, Florisil, and ion-exchanger. Chemically new bonded stationary phase
      development is also discussed. The improvement of the separations of some organic
      mixtures by impregnation of silica gel, cellulose, or polyamide plates (with
      transition metal ions and silver salts) and their applications is presented. The
      impregnation of the thin layer with organic stationary phase and inclusion
      complexes is another method used for the enhancement of the separation
      efficiences. Another modality to improve the selectivity in TLC using ion-pairing
      as reagent of impregnation is described as well. The actual state of chiral
      separation by TLC is discussed with concrete references to recent advances in
      chiral stationary phases. The use of nonpolar chemically bonded stationary phases
      impregnated with transitional metal ions is presented as chiral stationary
      phases. The cellulose, modified cellulose, chitin, chitosan, and their
      derivatives are presented and their potential for the analysis of the racemates
      is discussed. The cyclodextrines and macrocyclic antibiotics were used with very
      good results for enantiomeric separation by TLC. A new separation approach with
      molecular imprinting polymers was reported as a chiral stationary phase in TLC.
      The examples provide a wide range of structural types that can be readily
      resolved enantiomerically by TLC.

PMID- 12515357
TI  - Ultrathin-layer chromatography.
AB  - The development of ultrathin-layer silica gel plates with a monolithic structure
      opens up a new dimension in thin-layer chromatography (TLC). The very small layer
      thickness of approximately 10 microm and the absence of any kind of binder in
      combination with the framework of this stationary phase lead to new and improved
      properties of these ultrathin-layer chromatographic (UTLC) silica-gel plates
      compared with conventional TLC and high-performance TLC (HPTLC) precoated layers.
      First of all, the advantages of the UTLC plates are the very short migration
      distances and, in combination with this, the short development times as well as
      the very low consumption of solvents as the mobile phase in connection with high
      sensitivity. The separations of amino acids, pesticides, pharmaceutically active
      ingredients, phenols, and plasticizers effectively demonstrate the possibilities
      of the new ultrathin-layer silica-gel plates. Furthermore, a comparison of UTLC,
      HPTLC, and TLC concerning retention behavior, efficiency, detection limits,
      migration times, and solvent consumption is performed effectively by the
      separation of caffeine and paracetamol.

PMID- 12515358
TI  - Planar chromatographic method development using the PRISMA optimization system
      and flow charts.
AB  - This study presents a modern planar chromatographic method-development procedure,
      based on the "PRISMA" optimization system, in which the optimum separation is
      achieved systematically and the structures and properties of the substances to be
      separated are not known. The procedure consists of three stages. In the first of
      these the basic conditions the stationary phase, vapor phase, and individual
      solvents are selected with a TLC procedure (generally in nonsaturated
      chromatographic chambers). In the second stage, the optimum combination of the
      selected solvents is determined with the PRISMA model. The third part of the
      procedure includes the selection of the development mode (circular, linear, or
      anticircular); the selection of an appropriate forced-flow chromatographic
      technique (over-pressured layer chromatography or rotation planar chromatography)
      with high-performance thin-layer chromatographic plates; the transfer of the
      optimized mobile phase to the various analytical, planar, or column preparative
      liquid chromatographic techniques; and the selection of the operating conditions.
      For practical reasons, the optimization process is presented with the help of
      flow charts.

PMID- 12515359
TI  - Effect of TLC support characteristics and coating on the lipophilicity
      determination of phenols and aniline derivatives.
AB  - The lipophilicities of 18 ring-substituted phenol and aniline derivatives are
      determined on alumina and silica thin-layer chromatographic supports impregnated
      with 2.5 and 10% (v/v) paraffin oil in n-hexane using a mixture of water-methanol
      as the mobile phases. The effect of calculated physicochemical parameters and
      chromatographic conditions on the retention is elucidated by stepwise regression
      analyis. It is established that the degree of impregnation exerts a greater
      impact on the retention than the character of the support. Not only the
      calculated lipophilicity but also various sterical and polarity parameters
      significantly influence the retention, indicating the involvement of factors
      other than hydrophobic forces in the retention mechanism.

PMID- 12515360
TI  - Correlation between retention and 1-octanol-water partition coefficients of some
      estrane derivatives in reversed-phase thin-layer chromatography.
AB  - The retention constants (RM) of a series of estrane and secoestrane derivatives
      are experimentally determined on C18-modified silica gel layers with methanol
      water mobile phases of various concentrations. The slopes (m) and intercepts
      (RMW) of the linear relationships between RM and the volume fraction of methanol
      are calculated. Both constants increase when the retention of compounds
      increases, and there is a linear dependence between them indicating their
      additivity; they represent the sums of particular retention contributions of
      skeleton and substituents. The contributions, particularly the retention
      fragmental constants, are calculated by combining the linear relationships RM/log
      P, RM/m, and RMW/log P. The log P values of the compounds and skeleton were
      calculated using Rekker's fragmental constants.

PMID- 12515361
TI  - Comparison of different retention models in normal- and reversed-phase liquid
      chromatography with binary mobile phases.
AB  - The dependence on mobile phase composition of the retention of selected test
      analytes in different normal- and reversed-phase chromatographic systems is
      studied. The aim of this study is to compare the performance of six valuable
      retention models reported in the literature with a new empirical equation, which
      is first introduced in this study. All of these models are compared for different
      thin-layer chromatographic and high-performance liquid chromatographic systems by
      use of three criteria: the sum of the squared differences between the
      experimental and theoretical data, approximation of the standard deviation, and
      the Fisher test.

PMID- 12515362
TI  - OPLC and HPTLC methods in physicochemical studies of a new group of antimycotic
      compounds.
AB  - In this study two high-performance methods [overpressured layer chromatography
      (OPLC) and high-performance thin-layer chromatograpy (HPTLC) under reversed-phase
      conditions] are used to evaluate the hydrophobicity properties of newly
      synthesized bioactive compounds. The retention behavior of 24 2-(2,4
      dihydroxyphenyl)benzothiazoles are examined for acquisition of log k data. With
      water-methanol mixtures as the mobile phases, the concentration range in which
      the correlation between log k and methanol content is linear is established for
      both methods and used to determine the hydrophobicity parameters of log kw by
      linear extrapolation. The effect of substituents on retention constants is
      quantitated by using the group contribution parameters (tauw). The results
      suggest the use of OPLC methods for quick analysis of physicochemical properties
      of a large number of organic compounds.

PMID- 12515363
TI  - Plant drug analysis by planar chromatography.
AB  - Optimal performance laminar chromatography and automated multiple development
      chromatography are relatively recent techniques of planar chromatography that can
      be applied with success in plant material analysis. Therefore, these methods are
      used to study plant extracts and constituents belonging to different chemical
      classes of secondary metabolism: heterocyclic oxygen compounds (coumarins,
      flavonoids, and anthocyanins), alkaloids and quaternary ammonium salts,
      cannabinoids, essential oils, ginsenosides, and cardiac heterosides. Generally,
      the results obtained with these methods are good, and in most cases they compare
      with those of thin-layer chromatography.

PMID- 12515364
TI  - Uncertainty in quantitative thin-layer chromatography.
AB  - Globalization forces analysts to demand extended control of variability in
      analytical measurements. A calculation procedure named the "error budget model"
      following recommendations proposed more than 20 years ago by the Bureau
      International des Poids et Mesures is established as a rule for evaluating and
      expressing the measurement uncertainty across a broad spectrum of measurements.
      This metrological approach common in physical measurement is not applicable in
      separation techniques and cannot quantitate measurement uncertainty. Our
      experiments show that it can be used as a planning tool in the validation of thin
      layer chromatographic (TLC) methods. A computer program that quantitates
      uncertainty components associated with potential sources of uncertainty in
      quantitative TLC is prepared and tested with experimental data. TLC plates with
      different qualities of stationary phases (TLC and high-performance TLC) spotted
      with different types of samples are measured. Application is performed manually
      and automatically. Plates are scanned with UV-vis scanners and a video
      documentation system in remission and transmission mode and fluorescence.
      Although the calculated values are close to the values obtained with validation
      procedures, the error budget approach cannot substitute validation. Calculated
      results can predict critical points in real quantitative TLC, but they cannot
      confirm the validity of a selected chromatographic procedure.

PMID- 12515365
TI  - Metabolite analysis, isolation and purity assessment using various liquid
      chromatographic techniques combined with radioactivity detection.
AB  - During the discovery of metabolic routes of a drug candidate, radioactively
      labeled substances are administered. This study reports the multidimensional
      application of overpressured layer chromatography (OPLC) and high-performance
      liquid chromatography (HPLC) coupled with online or off-line nondestructive
      radioactivity detection methods in metabolism studies. Among these methods,
      digital autoradiography and flow-cell radioactivity detectors (RD) using solid
      scintillators are used. In this study, the hyphenation of OPLC with RD is
      reported. The application of the OPLC-RD technique is demonstrated on a
      metabolism study as well as the multidimensional chromatographic selectivity
      using normal-phase OPLC for the separation in the first dimension, followed by
      reversed-phase HPLC-RD, which provides additional selectivity to the separation.
      Information regarding the identity of radiolabeled metabolites and data obtained
      from spectroscopic methods could be advantageously used during structure
      elucidation.

PMID- 12515366
TI  - Combined thin-layer chromatography and mass spectrometry for the screening of
      pesticides in samples derived from biological origins.
AB  - This study describes a method for off-line coupling of thin-layer chromatography
      (TLC) with electron impact ionization (El)-mass spectrometry for routine
      determination of pesticides in toxicology and forensic medicine. Six TLC solvent
      systems are described for 151 different pesticides, and 8-peak mass-spectra
      generated from full El mass spectra are listed.

PMID- 12515367
TI  - Thin-layer chromatography--postsource-decay matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry of small drug molecules.
AB  - The structural analysis of small drug molecules by directly coupling thin-layer
      chromatography (TLC) with postsource-decay (PSD) matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry is reported. The applicability of
      this technique is shown using two examples: the TLC-PSD MALDI analysis of two
      representatives of nonsteroidal antiinflammatory drugs (tenoxicam and piroxicam)
      and the analysis of the pharmaceutically active compound UK-137,457 and one of
      its related substances UK-124,912. The matrices alpha-cyano-4-hydroxycinnamic
      acid (alpha-CHCA) and graphite are used to investigate the effect of the
      precursor ion selection on the TLC-PSD MALDI spectra of the drug molecules
      studied. Although alpha-CHCA enhances the [M+H]+ ion formation graphite produces
      in general only sodium adducts. Structural differentiation of tenoxicam and
      piroxicam is possible only by selecting the sodium adduct of both drug molecules
      as precursor ions. In the case of the TLC-PSD MALDI analysis of UK-137,457 and
      its related substance UK-124,912 at the 1% level, the PSD spectra obtained in
      alpha-CHCA by selecting the protonated adduct of the small molecules as precursor
      ions shows distinguishable dissociation patterns containing structurally
      significant information.

PMID- 12515368
TI  - Lupus nephritis: a nucleosome waste disposal defect?
AB  - Formation of anti-nuclear autoantibodies is a cardinal characteristic of systemic
      lupus erythematosus (SLE). In recent years the nucleosome has been identified as
      the major autoantigen, since nucleosome specific T cells have been identified,
      which also drive the formation of anti-dsDNA and anti-histone antibodies.
      Nucleosome specific autoantibodies are present in a large majority of SLE
      patients and lupus mice. Nucleosomes are formed during apoptosis by organized
      cleavage of chromatin. These nucleosomes together with other lupus autoantigens
      cluster in apoptotic bodies at the surface of apoptotic cells. Systemic release
      of these autoantigens is normally prevented by swift removal of apoptotic cels.
      However, if the rate of apoptosis overflows the removal capacity and/or the
      cleaning machinery is reduced, nucleosomes are released. Furthermore, during
      apoptosis autoantigens can be modified, which makes them more immunogenic.
      Nucleosomes also play a pivotal role in the evolution of tissue lesions,
      especially glomerulonephritis. In lupus nephritis nucleosomes, anti-nucleosome
      autoantibodies and nucleosome/Ig complexes have been identified in the glomerular
      immune deposits. Via their cationic histone part nucleosomes can bind to heparan
      sulfate, a strong anionic constituent of the glomerular basement membrane.

PMID- 12515369
TI  - Rewriting the histological classification of lupus nephritis.
AB  - The World Health Organization (WHO) classification of lupus (SLE) nephritis was
      published almost 20 years ago, and there is world-wide recognition of its utility
      in the diagnosis and treatment of SLE glomerulonephritis (GN). However, a number
      of problems have been recognized: The classification of severe segmental (WHO
      class III > or = 50%) and membranous glomerulonephritis (MGN) complicated by the
      lesions of severe segmental or diffuse GN (WHO classes Vc > or = 50% or Vd) is
      ambiguous; The implications of non-immune complex pathogenic mechanisms are not
      acknowledged and SLE interstitial nephritis and vasculitis are not included in
      the current classification. We propose a revision that retains the classes of the
      current WHO classification. Informed by investigations utilizing the WHO
      classification, it places severe segmental GN in class III (segmental GN) and
      mixed MGN and segmental and diffuse GN in class V (MGN). It optimizes the use of
      electron and fluorescence microscopy in defining controversial and ambiguous
      lesions. It develops subclasses based upon pathogenic insights gained since the
      advent of the WHO classification. Finally, it recognizes the need to include the
      disease specific lesions of SLE tubulointerstial nephritis and vasculitis.

PMID- 12515370
TI  - The use of laboratory tests in diagnosis and monitoring of systemic lupus
      erythematosus.
AB  - Clinical immunology laboratories play an essential role in diagnosis and
      monitoring of systemic lupus erythematosus (SLE). To obtain the best results in
      terms of diagnostic performance and clinical usefulness, the following
      recommendations should be fulfilled: Indirect immunofluorescence on Hep-2 cells
      remains the method of choice for the detection of anti-nuclear antibodies (ANA).
      The sensitivity of ANA test for SLE is very high (almost 100%) but its
      specificity low since ANA can be present in a number of different clinical
      conditions and even in normal controls. Anti-dsDNA antibodies are highly specific
      for SLE and present in a high proportion of SLE patients (40-80%). The method of
      choice for anti-ds DNA is the Farr assay; however, the necessity of using
      radioactive material decreases its applicability. As an alternative,
      immunofluorescence on Crithidia Luciliae can be used in the diagnostic phase for
      its high specificity. It is not advisable to use ELISA, in the diagnostic phase,
      due to its low specificity. The quantitative determination of anti-dsDNA is
      useful for monitoring patients, in particular in the presence of nephritis. For
      monitoring, a quantitative method should be used (Farr assay or ELISA). The
      detection of antibodies to extractable nuclear antigens (ENA) and to
      phospholipids (Lupus anticoagulant and anti-cardiolipin antibodies with a beta2
      glycoprotein I-dependent method) are useful to identify subgroups of patients at
      risk for some clinical manifestations (i.e. anti-phospholipid syndrome). New
      assays (anti-C1q and anti-nucleosome antibodies) have been recently proposed for
      diagnosis (anti-nucleosome) and monitoring SLE patients (anti-C1q and anti
      nucleosome antibodies), with promising results. Among biological parameters,
      urinary levels of monocyte chemoattranct protein 1 (MCP1) seem to be the most
      useful to monitor nephritis activity in lupus patients.

PMID- 12515371
TI  - Vascular access in the 21st century.
AB  - Worldwide, aged diabetic patients represent the most rapidly growing group of
      patients treated for endstage renal disease (ESRD). Pre-existing arterial as well
      as venous problems have led to a pessimistic view on the creation of vascular
      access in the future. In addition, more and more patients undergo hemodialysis
      therapy for twenty or thirty years with obvious vascular wastage. Personal
      experience in the interdisciplinary field of vascular access covering nephrology,
      vascular surgery and radiology clearly show that history is a good teacher. Since
      the introduction of the surgically created arterio-venous fistula by Brescia and
      Cimino in 1966, only minor progress has been seen; widespread use of different
      graft materials has produced mainly disappointing results, thus contributing to
      more temporary or permanent central venous catheters. Despite better catheter
      technology, essential problems like infection and thrombosis have not changed.
      The challenge for the 21st century is to find strategies and solutions to face
      these deteriorated conditions. The factors contributing to adequate vascular
      access are: an individually tailored approach with clear preference for native
      vessels, respecting basic hemodynamic rules, analysing past failures, combining
      careful preoperative investigations and meticulous surgical technique; continuous
      surveillance of fistula function and early, elective revision to prolong the
      lifespan of vascular access. An interdisciplinary team will be essential to
      achieve this goal.

PMID- 12515372
TI  - Dialysis for everybody? At any cost?
AB  - During the last fifty years medicine has made enormous progress. However the
      "mechanical disease model" has introduced the concept of disease as a biological
      disorder and, at the same time, has shifted the objective of the doctor's action:
      the patient is identified with the disease and the latter being curable, there
      are no limits to the doctor's action. This behaviour has two different
      implications: one is referred to the tremendous increase of the expenditure and
      the second is related to the changes in death's physiognomy. Today death is no
      longer a moment, but a process whose practical outcome is the dilution (from
      hours to months) of the boundary between life and death. Equity is one of the
      main principles of every health systems: all the members of a community should
      have equal opportunities to receive medical treatment. Every year approximately
      1250 million Euros (2% of the total health expenditure) are spent in Italy for
      nearly 41,000 patients on chronic dialysis. In terms of macro economy and of
      balanced health policy, no ethical principles can justify the absorption of such
      a huge quantity of resources by such a small number of patients. We must
      establish some rules, but it is obvious that such rules cannot be based on the
      identification of criteria that exclude patient groups based on statistical
      parameters, and on the sum of risk factors. Viceversa, the exclusion and/or
      withdrawal from RRT must depend on the possibilities of individual patients to
      maintain the essential characteristics of human beings or on the patient's
      opinion that there is a lack of proportion between means and results. Doctors
      cannot presume that the best solution coincides with the extension of patients'
      life. Their assistance must not aim at mere survival neglecting the quality of
      life. In order to start an in depth discussion, solid ethical and methodological
      references can be found in the "Clinical Practice Guidelines on Shared Decision
      Making in the Appropriate Initiation of and Withdrawal from Dialysis". This topic
      can no longer be postponed. Should the nephrological community be unable to find
      a shared basis for discussion beyond hypocrisy, the valuable doctor-patient
      relationship (which is vital for all medical procedures) will be replaced by the
      "taxpayer-mediated" approach. In this case, following the principles of social
      good, the political community will compel doctors to mediate a conflict between
      collective interests and individual interests, and doctors will no longer be able
      to act in compliance with the ethical principles of "avoiding harm".

PMID- 12515373
TI  - Monogenic renal diseases: a clinical introduction.
AB  - The clinical spectrum of monogenic renal diseases is wide ranging, from autosomal
      dominant polycystic kidney disease to very rare inherited disorders. The genes
      involved in most of these diseases have been identified. However some monogenic
      diseases are still not characterized clinically. The challenges of the future
      will be to understand phenotypic variability and the molecular mechanisms of
      disease, and to design pharmacological tools to stop or retard its progression.
      The post-gene era has begun and the field of research in monogenic disorders is
      wide open.

PMID- 12515374
TI  - Glomerular changes in hereditary single-gene diseases.
AB  - Molecular genetics has strongly influenced clinical medicine and particularly
      nephrology. Several gene mutations of single-gene hereditary nephropathies have
      been recently identified. These data are useful to develop methods of diagnosis
      and treatment, but also to understand the pathogenesis of these particular
      disorders. In this review we focused on several monogenic hereditary renal
      diseases inducing nephrotic syndrome and other hereditary diseases with renal
      involvement and progression towards end-stage renal failure.

PMID- 12515375
TI  - Monogenic tubular salt and acid transporter disorders.
AB  - In this review I will briefly discuss two major categories of inherited renal
      tubular transport disorders: those primarily affecting sodium and potassium
      (whether retention or wasting), and the primary renal acidopathies. The kidney
      does not of course carry out any of its myriad homeostatic functions in a vacuum,
      and interactions with other systems form an important part of the overall
      picture. This is perhaps most marked in the context of salt homeostasis, where
      the endocrine system, particularly the mineralocorticoid axis and aldosterone,
      are closely dovetailed. While these disorders are in general rare, the insights
      gained in understanding their molecular bases have added significantly to our
      understanding of normal human physiology. The hope is that these findings may in
      the future prove relevant to the understanding and treatment of more common
      disorders.

PMID- 12515376
TI  - Echo-doppler to predict the outcome for renal artery stenosis.
AB  - Not all patients with renal artery stenosis will benefit from angioplasty or
      surgery. For this reason it is not sufficient to diagnose the presence of renal
      artery stenosis, but one also has to evaluate its functional significance.
      Ultrasonographic detection of renal artery stenosis can be made with a
      sensitivity and specificity exceeding 90% by an experienced investigator. A
      combination of Doppler parameters making use of both direct and indirect signs of
      stenosis should be used. In our hands, a renal-renal ratio greater than 4 and--if
      this parameter was not measurable--an acceleration time longer than 70 msec was
      the best combination. The reversibility of hypertension or impaired renal
      function (i.e. the presence of renovascular hypertension or azotemia) after
      successful correction of renal artery stenosis can be assessed by measuring
      segmental artery resistance indices. A resistance index value greater than 0.80
      makes a treatment effect highly unlikely, and these patients should not undergo
      angioplasty or surgery of their stenosis.

PMID- 12515377
TI  - Electron beam tomography to image cardiovascular calcifications in hemodialysis
      patients.
AB  - Cardiovascular disease is the leading cause of death in western countries and it
      is especially frequent in dialysis patients. Though for a long time physicians
      have been mainly focused on the severity of luminal coronary stenosis,
      atherosclerosis starts and expands in the contest of the arterial wall much
      before it extends into the vessel lumen. Indeed, most acute coronary events occur
      in patients with non-obstructive luminal disease. On pathological examination
      patients with end stage renal disease (ESRD) show larger and more extensively
      calcified atherosclerotic lesions than non-uremic patients. Recent evidence shows
      that even very young dialysis patients show premature calcification of the
      coronary arteries. Therefore, early detection of atherosclerotic disease with a
      non-invasive imaging technology such as electron beam tomography (EBT) may
      provide an opportunity to modify the disease course and reduce the related event
      rate.

PMID- 12515378
TI  - Vascular calcification in end-stage renal disease.
AB  - Vascular calcification is common in patients with end-stage renal disease (ESRD)
      who are treated with regular dialysis, and it may contribute to the very high
      mortality rate from cardiovascular causes in such patients. Arterial
      calcification in those with chronic renal failure can result from the deposition
      of mineral along the intimal layer of arteries in conjunction with
      atherosclerotic plaques or from calcium deposition in the medial wall of arteries
      that is due, at least in part, to disturbances in mineral metabolism. Several
      reports indicate that coronary artery calcification as measured by electron-beam
      computed tomography (EBCT) is common and often quite extensive in patients with
      ESRD, but the clinical significance of this finding remains uncertain. EBCT
      measurements of coronary artery calcification have been shown to be a useful
      marker of atherosclerotic burden in the general population, and values serve to
      predict the risk of adverse cardiovascular events. By contrast, the relationship
      between coronary artery calcification scores as measured by EBCT and clinically
      significant coronary artery lesions has not been studied adequately in patients
      with ESRD. Indeed, calcium accumulation in the coronary arteries and other
      systemic vessels in patients with chronic renal failure is probably attributable
      to both intimal and medial wall calcification. Concurrent assessments using
      coronary angiography and EBCT are needed to determine the diagnostic value of
      EBCT as a predictor of cardiovascular disease in patients with ESRD. Despite the
      shortcomings of currently available data, the technique of EBCT makes it possible
      to detect the presence and to monitor the progression of coronary calcification
      in those undergoing long-term dialysis. Studies using this non-invasive
      diagnostic method may provide important new information about factors that
      initiate the development and mediate the progression of arterial calcification in
      patients with ESRD.

PMID- 12515379
TI  - Bone disease in uremic patients: advances in PTH suppression.
AB  - Chronic renal failure is often complicated by altered calcium and phosphate
      omeostasis. Many patients develop secondary hyperparathyroidism during the course
      of the disease. Therefore, both prevention and treatment of secondary
      hyperparathyroidism are central issues in the treatment of uremic patients.
      Active vitamin D metabolites are important agents in uremic patients, who have a
      defective activity of the renal 1alpha-hydroxylase responsible for calcitriol
      synthesis. Howewer, treatment with calcitriol has some limitations, namely an
      increase in intestinal phosphate absorption, a possible calcium overload and
      therefore an increase in CaxP ion product. These limitations stimulated an active
      research on the development of vitamin D analogs with reduced effects on
      intestinal transport as well as on bone mobilization of calcium and phosphate.
      Three vitamin D analogs, which have been used in humans, are reviewed in this
      article: 22-oxacalcitriol (Maxacalcitol), 19-nor-1alpha,25(OH)2 vitamin D2
      (Paricalcitol), and 1alpha(OH) Vitamin D2 (Doxercalciferol). In addition, a new
      pharmacologic approach to the treatment of secondary hyperparathyroidism has been
      developed: the use of agonists for the parathyroid calcium sensing receptor, or
      calcimimetics. AMG O73, a second generation agent, is now under clinical
      evaluation in phase 3 studies, and it will soon be available in clinical
      practice. Given the different mechanism of action, it will be possible to use it
      along with vitamin D analogs and non calcemic phosphate binders. A broader
      spectrum of therapeutic approaches will enable the nephrologist to individually
      tailor the treatment of secondary hyperparathyroidism.

PMID- 12515380
TI  - Identification of cells deficient in signaling-induced alternative splicing by
      use of somatic cell genetics.
AB  - In recent years, a growing number of mammalian genes have been shown to undergo
      alternative splicing in response to extracellular stimuli. However, the factors
      and pathways involved in such signal-induced alternative splicing are almost
      entirely unknown. Here we describe a novel method for identifying candidate trans
      acting factors that are involved in regulating mammalian alternative splicing,
      using the activation-induced alternative splicing of the human CD45 gene in T
      cells as a model system. We generated a cell line that stably expresses a CD45
      minigene-based GFP reporter construct, such that the levels of green-fluorescent
      protein (GFP) expressed in the cell reflect the splicing state of the endogenous
      CD45 gene. Following mutagenesis of this cell line, and multiple rounds of
      selection for cells that displayed aberrant levels of GFP expression, we isolated
      several cell lines that are at least partially defective in their ability to
      support regulated alternative splicing of endogenous CD45 pre-mRNA in response to
      cell stimulation. Thus we have successfully isolated mutants in a mammalian
      alternative splicing pathway through use of a somatic cell-based genetic screen.
      This study clearly demonstrates the feasibility of using genetic screens to
      further our understanding of the regulation of mammalian splicing, particularly
      as it occurs in response to environmental cues.

PMID- 12515381
TI  - Reduced FMR1 mRNA translation efficiency in fragile X patients with premutations.
AB  - The Fragile X mental retardation gene (FMR1) contains a polymorphic trinucleotide
      CGG repeat in the 5' untranslated region (UTR) of the FMR1 messenger. We have
      characterized three lymphoblastoid cell lines derived from unrelated male
      carriers of a premutation that overexpress FMR1 mRNA and show reduced FMRP level
      compared to normal cells. The analysis of polysomes/mRNPs distribution of mRNA in
      the cell lines with a premutation shows that the polysomal association of FMR1
      mRNA, which is high in normal cells, becomes progressively lower with increasing
      CGG repeat expansion. In addition, we could detect a very low level of FMR1 mRNA
      in a lymphoblastoid cell line from a patient with a full mutation. In this case,
      FMR1 mRNA is not at all associated with polysomes, in agreement with the complete
      absence of FMRP. The impairment of FMR1 mRNA translation in patients with the
      Fragile X syndrome with FMR1 premutation is the cause of the lower FMRP levels
      that leads to the clinical involvement.

PMID- 12515382
TI  - The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and
      Xrnl in distinct cytoplasmic foci.
AB  - Sm and Sm-like (LSm) proteins form heptameric complexes that are involved in
      various steps of RNA metabolism. In yeast, the Lsm1-7 complex functions in mRNA
      degradation and is associated with several enzymes of this pathway, while the
      complex LSm2-8, the composition of which largely overlaps with that of LSm1-7,
      has a role in pre-mRNA splicing. A human gene encoding an LSm1 homolog has been
      identified, but its role in mRNA degradation has yet to be elucidated. We
      performed subcellular localization studies and found hLSm1 predominantly in the
      cytoplasm. However, it is not distributed evenly; rather, it is highly enriched
      in small, discrete foci. The endogenous hLSm4 is similarly localized, as are the
      overexpressed proteins hLSm1-7, but not hLSm8. The foci also contain two key
      factors in mRNA degradation, namely the decapping enzyme hDcp1/2 and the
      exonuclease hXrn1. Moreover, coexpression of wild-type and mutant LSm proteins,
      as well as fluorescence resonance energy transfer (FRET) studies, indicate that
      the mammalian proteins hLSm1-7 form a complex similar to the one found in yeast,
      and that complex formation is required for enrichment of the proteins in the
      cytoplasmic foci. Therefore, the foci contain a partially or fully assembled
      machinery for the degradation of mRNA.

PMID- 12515383
TI  - Naf1 p is a box H/ACA snoRNP assembly factor.
AB  - Box H/ACA small nucleolar ribonucleoprotein particles (snoRNPs) contain four
      essential proteins, Cbf5p, Gar1p, Nhp2p, and Nop10p, each of which, with the
      exception of Gar1p, is required for box H/ACA snoRNA accumulation. Database
      searches identified a novel essential protein, which we termed Naf1p, with a
      region of homology to the RNA-binding domain of Gar1p and other features in
      common with hnRNP-like proteins. Naf1p is localized to the nucleus and is not a
      stable component of the H/ACA snoRNPs, but it is required for the accumulation of
      all box H/ACA snoRNAs. This requirement is not at the level of snoRNA
      transcription initiation or termination. Naf1 p shows in vitro RNA-binding
      activity and also binds directly to Cbf5p and Nhp2p. Naf1p was shown to bind to
      the CTD in vivo in a two-hybrid assay, and the phosphorylated CTD, but not the
      nonphosphorylated CTD, was shown to precipitate tagged Naf1p from a cell lysate.
      We propose that Naf1 p is recruited to the CTD of RNA polymerase II and binds to
      nascent box H/ACA snoRNAs promoting snoRNP assembly.

PMID- 12515384
TI  - An H/ACA guide RNA directs U2 pseudouridylation at two different sites in the
      branchpoint recognition region in Xenopus oocytes.
AB  - U2 is the most extensively modified of all spliceosomal snRNAs. We previously
      showed that at least some of the internally modified nucleotides in U2 snRNA are
      required for snRNP biogenesis and pre-mRNA splicing. Recent work from several
      laboratories suggests that nuclear guide RNAs facilitate U2 snRNA internal
      modification, including pseudouridylation and 2'-O-methylation. Here, we present
      a novel approach to identifying guide RNAs for U2 pseudouridylation. Several
      Xenopus oocyte nuclear RNAs were affinity selected with U2 snRNA substituted with
      5-fluorouridine, a pseudouridylation inhibitor that sequesters pseudouridylases.
      One of these RNAs was sequenced and found to be a novel RNA of 134 nt. This small
      RNA contains an H/ACA motif and folds into a typical H/ACA RNA structure, and its
      authenticity as an H/ACA RNA was confirmed by immunoprecipitation analysis. The
      RNA contains two guide sequences for pseudouridylation (psi) of U2 snRNA at
      positions 34 and 44 in the branch-site recognition region, and we demonstrate
      that this RNA indeed guides the formation of psi34 and psi44 in U2 using a
      Xenopus oocyte reconstitution system. Therefore, this novel RNA was designated
      pugU2-34/44, for pseudouridylation guide for U2 snRNA U34 and U44. Intranuclear
      localization analyses indicate that pugU2-34/44 resides within the nucleoplasm
      rather than nucleoli or Cajal bodies where other guide RNAs have been localized.
      Our results clarify the mechanism of U2 snRNA pseudouridylation in Xenopus
      oocytes, and have interesting implications with regard to the intranuclear
      localization of U2 snRNA pseudouridylation.

PMID- 12515385
TI  - Regulated alpha-globin mRNA decay is a cytoplasmic event proceeding through 3'-to
      5' exosome-dependent decapping.
AB  - The alpha-globin mRNA contains a C-rich stability element (CRE) in its 3'
      untranslated region (3' UTR) which is critical for the stability of this long
      lived mRNA. A protein complex, termed the alpha-complex, forms on the CRE and has
      been shown to contribute to stabilization of the mRNA by at least two mechanisms,
      first by interacting with the poly(A)-binding protein (PABP) to prevent
      deadenylation, and second by protecting the mRNA from attack by an erythroid
      endoribonuclease. In this report, we demonstrate that the alpha-globin 3' UTR can
      confer stability on a heterologous mRNA in cells, and this stability is dependent
      on the alpha-complex. Moreover, the stability was exclusively detected with
      cytoplasmic mRNA, suggesting that the regulation of alpha-globin mRNA stability
      is a cytoplasmic event. An additional mechanism by which the alpha-complex can
      confer stability on an RNA in vitro was also identified and shown to involve
      inhibition of 3' to 5' exonucleolytic degradation. Furthermore, using an in vitro
      mRNA decay system, we were able to follow the demise of the alpha-globin RNA and
      demonstrate that the decay was initiated by deadenylation followed by 3'-to-5'
      decay carried out by the exosome and ultimately hydrolysis of the residual cap
      structure.

PMID- 12515386
TI  - UM 9(5)h and UM 9(5)p, human and porcine noncoding transcripts with preferential
      expression in the cerebellum.
AB  - We compared the gene expression patterns of fetal and adult porcine brains and
      identified a sequence tag that was more abundant in adult than in fetal brain.
      The RNA corresponding to the sequence tag has the highest expression level in
      adult cerebellum. Lower expression levels of the transcript were found in adult
      cerebrum, pituitary, and uterus, as well as in fetal brain, heart, intestine,
      kidney, and liver. The sequence tag was used to screen a cDNA library from adult
      porcine brain. Two independent clones of 2,273 nt and 1,701 nt were isolated. The
      shorter cDNA is a 5'-truncated form of the longer clone, and both clones have
      almost identical sequences with multiple start and stop codons in all three
      reading frames. Screening of two different human brain cDNA libraries with
      porcine cDNA probes resulted in four overlapping cDNA fragments, which were
      assembled to one contig of 2,336 nt in length. Like noncoding RNAs, the porcine
      and human sequences have no common conserved open reading frame and share
      stretches of high homology interrupted by stretches with almost no homology. The
      human and porcine RNAs were named UM 9(5)h and UM 9(5)p, respectively. They are
      part of larger transcripts, which are transcribed from single-copy genes, they
      have very similar tissue distributions, and their sequences are colinear with the
      respective genomic fragment.

PMID- 12515387
TI  - Detailed analysis of RNA-protein interactions within the bacterial ribosomal
      protein L5/5S rRNA complex.
AB  - The crystal structure of ribosomal protein L5 from Thermus thermophilus complexed
      with a 34-nt fragment comprising helix III and loop C of Escherichia coli 5S rRNA
      has been determined at 2.5 A resolution. The protein specifically interacts with
      the bulged nucleotides at the top of loop C of 5S rRNA. The rRNA and protein
      contact surfaces are strongly stabilized by intramolecular interactions. Charged
      and polar atoms forming the network of conserved intermolecular hydrogen bonds
      are located in two narrow planar parallel layers belonging to the protein and
      rRNA, respectively. The regions, including these atoms conserved in Bacteria and
      Archaea, can be considered an RNA-protein recognition module. Comparison of the
      T. thermophilus L5 structure in the RNA-bound form with the isolated Bacillus
      stearothermophilus L5 structure shows that the RNA-recognition module on the
      protein surface does not undergo significant changes upon RNA binding. In the
      crystal of the complex, the protein interacts with another RNA molecule in the
      asymmetric unit through the beta-sheet concave surface. This protein/RNA
      interface simulates the interaction of L5 with 23S rRNA observed in the
      Haloarcula marismortui 50S ribosomal subunit.

PMID- 12515388
TI  - The influence of viral coding sequences on pestivirus IRES activity reveals
      further parallels with translation initiation in prokaryotes.
AB  - Classical swine fever virus (CSFV) is a member of the pestivirus family, which
      shares many features in common with hepatitis C virus (HCV). It is shown here
      that CSFV has an exceptionally efficient cis-acting internal ribosome entry
      segment (IRES), which, like that of HCV, is strongly influenced by the sequences
      immediately downstream of the initiation codon, and is optimal with viral coding
      sequences in this position. Constructs that retained 17 or more codons of viral
      coding sequence exhibited full IRES activity, but with only 12 codons, activity
      was approximately 66% of maximum in vitro (though close to maximum in transfected
      BHK cells), whereas with just 3 codons or fewer, the activity was only
      approximately 15% of maximum. The minimal coding region elements required for
      high activity were exchanged between HCV and CSFV. Although maximum activity was
      observed in each case with the homologous combination of coding region and 5'
      UTR, the heterologous combinations were sufficiently active to rule out a highly
      specific functional interplay between the 5' UTR and coding sequences. On the
      other hand, inversion of the coding sequences resulted in low IRES activity,
      particularly with the HCV coding sequences. RNA structure probing showed that the
      efficiency of internal initiation of these chimeric constructs correlated most
      closely with the degree of single-strandedness of the region around and
      immediately downstream of the initiation codon. The low activity IRESs could not
      be rescued by addition of supplementary eIF4A (the initiation factor with ATP
      dependent RNA helicase activity). The extreme sensitivity to secondary structure
      around the initiation codon is likely to be due to the fact that the eIF4F
      complex (which has eIF4A as one of its subunits) is not required for and does not
      participate in initiation on these IRESs.

PMID- 12515389
TI  - Selection of antisense oligodeoxynucleotides against glutathione S-transferase
      Mu.
AB  - The aim of the present study was to identify functional antisense
      oligodeoxynucleotides (ODNs) against the rat glutathione S-transferase Mu (GSTM)
      isoforms, GSTM1 and GSTM2. These antisense ODNs would enable the study of the
      physiological consequences of GSTM deficiency. Because it has been suggested that
      the effectiveness of antisense ODNs is dependent on the secondary mRNA structures
      of their target sites, we made mRNA secondary structure predictions with two
      software packages, Mfold and STAR. The two programs produced only marginally
      similar structures, which can probably be attributed to differences in the
      algorithms used. The effectiveness of a set of 18 antisense ODNs was evaluated
      with a cell-free transcription/translation assay, and their activity was
      correlated with the predicted secondary RNA structures. Four phosphodiester ODNs
      specific for GSTM1, two ODNs specific for GSTM2, and four ODNs targeted at both
      GSTM isoforms were found to be potent, sequence-specific, and RNase H-dependent
      inhibitors of protein expression. The IC50 value of the most potent ODN was
      approximately 100 nM. Antisense ODNs targeted against regions that were predicted
      by STAR to be predominantly single stranded were more potent than antisense ODNs
      against double-stranded regions. Such a correlation was not found for the Mfold
      prediction. Our data suggest that simulation of the local folding of RNA
      facilitates the discovery of potent antisense sequences. In conclusion, we
      selected several promising antisense sequences, which, when synthesized as
      biologically stable oligonucleotides, can be applied for study of the
      physiological impact of reduced GSTM expression.

PMID- 12515390
TI  - The DPE, a core promoter element for transcription by RNA polymerase II.
AB  - The core promoter is an important yet often overlooked component in the
      regulation of transcription by RNA polymerase II. In fact, the core promoter is
      the ultimate target of action of all of the factors and coregulators that control
      the transcriptional activity of every gene. In this review, I describe our
      current knowledge of a downstream core promoter element termed the DPE, which is
      a TFIID recognition site that is conserved from Drosophila to humans. The DPE is
      located from +28 to +32 relative to the +1 transcription start site, and is
      mainly present in core promoters that lack a TATA box motif. Moreover, in
      Drosophila, the DPE appears to be about as common as the TATA box. There are
      distinct mechanisms of basal transcription from DPE- versus TATA-dependent core
      promoters. For instance, NC2/Dr1-Drap1 is a repressor of TATA-dependent
      transcription and an activator of DPE-dependent transcription. In addition, DPE
      specific and TATA-specific transcriptional enhancers have been identified. These
      findings further indicate that the core promoter is an active participant in the
      regulation of eukaryotic gene expression.

PMID- 12515391
TI  - Optimal salt concentration of vehicle for plasmid DNA enhances gene transfer
      mediated by electroporation.
AB  - In vivo electroporation has emerged as a leading technology for developing
      nonviral gene therapies, and the various technical parameters governing
      electroporation efficiency have been optimized by both theoretical and
      experimental analysis. However, most electroporation parameters focused on the
      electric conditions and the preferred vehicle for plasmid DNA injections has been
      normal saline. We hypothesized that salts in vehicle for plasmid DNA must affect
      the efficiency of DNA transfer because cations would alter ionic atmosphere,
      ionic strength, and conductivity of their medium. Here, we show that half saline
      (71 mM) is an optimal vehicle for in vivo electroporation of naked DNA in
      skeletal muscle. With various salt concentrations, two reporter genes, luciferase
      and beta-galactosidase were injected intramuscularly under our optimal electric
      condition (125 V/cm, 4 pulses x 2 times, 50 ms, 1 Hz). Exact salt concentrations
      of DNA vehicle were measured by the inductively coupled plasma-atomic emission
      spectrometer (ICP-AES) and the conductivity change in the tissue induced by the
      salt in the medium was measured by Low-Frequency (LF) Impedance Analyzer.
      Luciferase expression increased as cation concentration of vehicle decreased and
      this result can be visualized by X-Gal staining. However, at lower salt
      concentration, transfection efficiency was diminished because the hypoosmotic
      stress and electrical injury by low conductivity induced myofiber damage. At
      optimal salt concentration (71 mM), we observed a 3-fold average increase in
      luciferase expression in comparison with the normal saline condition (p < 0.01).
      These results provide a valuable experimental parameter for in vivo gene therapy
      mediated by electroporation.

PMID- 12515392
TI  - Synergistic effect of peroxiredoxin II antisense on cisplatin-induced cell death.
AB  - Peroxiredoxin II (Prx II) is known not only to protect cells from oxidative
      damage caused by hydrogen peroxide (H202), but also to endow cancer cells with
      resistance to both H202 and cisplatin and to grant them radioresistance. In this
      study, we examined whether Prx II antisense could enhance cisplatin-induced cell
      death. When gastric cancer cells were transfected with various concentrations of
      Prx II antisense plasmid, pPrxII/AS, and then treated with the same
      concentrations of cisplatin, Prx II antisense enhanced cisplatin-induced cell
      death. The combination index (CI) at all doses of the combination was below 1,
      indicating that Prx II antisense sensitized cisplatin-induced cell death. This
      synergism was also observed in the cells transfected with a Prx II antisense
      oligomer. Our present results, therefore, suggest that Prx II antisense would be
      a very good sensitizer for cisplatin, and that Prx II as a target for
      chemosensitizers constitutes a promising avenue for future research.

PMID- 12515393
TI  - Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular
      endothelial growth factor gene after myocardial injection of naked DNA.
AB  - Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid
      DNA into the myocardium was shown to induce development of new blood vessels to
      increase the circulation in the heart of patients with coronary artery diseases.
      However, such angiogenic gene therapy (via naked DNA) was limited by low level of
      gene expression. Furthermore, the temporal and spatial characteristics of VEGF
      gene transfer in the heart are not known. In this study, we demonstrated that a
      plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE)
      promoter and enhancer, induces greater expression of gene in the rat heart
      monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter,
      than four different viral and cellular promoters. Interestingly, expression of
      VEGF121 protein showed an earlier peak, a shorter duration, and a wider
      distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE
      promoter/enhancer provides clear advantages over other previously developed
      plasmids. Furthermore, expression profile of VEGF121 gene may provide useful
      information in the design of angiogenic gene therapy in the heart.

PMID- 12515394
TI  - Intracellular trafficking and metabolic turnover of yeast prepro-alpha-factor
      SRIF precursors in GH3 cells.
AB  - Chimeric genes coding for prepro region of yeast alpha-factor and anglerfish SRIF
      were expressed in rat GH3 cells to determine whether yeast signals could regulate
      hormone processing in mammalian cells. We report that nascent hybrid polypeptides
      were efficiently targeted to ER, where cleavage of signal peptides and core
      glycosylation occurred, and were localized mainly in Golgi. These data indicate
      that prepro region of yeast alpha-factor functions in sorting molecules to
      secretory pathway in mammalian cells. A hybrid construct with a mutated signal
      peptide underwent similar ER translocation, whereas such a mutation resulted in
      defective translocation in yeast (Cheong et al., 1997). This difference may be
      due to the differences in ER translocation between yeast and mammalian cells,
      i.e., posttranslational versus cotranslational translocation. Processing and
      secretion of metabolically labeled hybrid propeptides to mature SRIF peptides
      were assessed by HPLC. When pulse-labeled cells were chased for up to 2 h,
      intracellular propeptides disappeared with a half-life of approximately 25 min,
      showing that approximately 68% of initially synthesized propeptides were secreted
      constitutively. About 22% of SRIF-related products were proteolytically processed
      to mature SRIF, of which 38.7% were stored intracellularly with a half-life of
      approximately 2 h. In addition, immunocytochemical localization showed that a
      small proportion of SRIF molecules accumulated in secretory vesicles. All these
      results suggest that yeast prepropeptide could direct hybrid precursors to
      translocate into ER lumen and transit through secretory pathway to the distal
      elements of Golgi compartment, but could process and target it less efficiently
      to downstream in rat endocrine cells.

PMID- 12515395
TI  - Evaluation of a Apo-1/Fas promoter polymorphism in Korean stroke patients.
AB  - Apoptosis has been implicated in the pathogenesis of neurodegenerative diseases
      such as stroke and Alzheimer's disease. Apo-1/Fas gene is one of the mediators of
      apoptosis in stroke. Mval polymorphism is the first polymorphic marker identified
      in the Apo-1/Fas gene promoter, which was typed by PCR and followed by Mval
      digestion and gel electrophoresis. DNA isolated from peripheral blood collected
      from 91 stroke patients and 103 healthy blood donors was used for genotypes of
      GG, GA and AA by sequence specific primer PCR. Mval polymorphism was examined
      based on Fas gene promotor region by restriction fragment length polymorphism
      (RFLP). The Fas-GG genotype was the least frequent in patients with stroke and
      healthy controls (P = 0.57). In normal Korean controls the Mval polymorphism GA,
      AA and GG were 48.6%, 34.9% and 16.5%. In stroke patients were 56.2%, 29.6% and
      14.2% respectively. And the allelic frequencies of Mval*2 (G) allele were less
      frequent than Mval*1 (A) allele in patients with stroke and healthy controls (P =
      0.76). In normal Korean controls Mval*1 (A) and Mval*2 (G) alleles were 59.2% and
      40.8%. In stroke patients were 57.6% and 42.4%, respectively. Our results,
      pending confirmation in a larger study, indicate that the Fas genotype may not
      appear to be a risk factor for stroke in Korean stroke patients.

PMID- 12515396
TI  - Catheter-based adenovirus-mediated local intravascular gene delivery of a soluble
      TGF-beta type II receptor using an infiltrator in porcine coronary arteries:
      efficacy and complications.
AB  - Enhanced extracellular matrix (ECM) accumulation is an important finding in human
      restenotic arterial neointima after angioplasty. Transforming growth factor
      beta1(TGF-beta1) is known to regulate the synthesis and turnover of a variety of
      ECM components, and may play an important role in restenosis. Recombinant
      adenoviral vector expressing an ectodomain of the TGF-beta type II receptor fused
      to the human immunoglobulin Fc portion (AdTbeta-ExR) inhibits the action of TGF
      beta probably either by adsorbing TGF-beta or by acting as a dominant negative
      receptor. We carried out a catheter-based local adenovirus mediated gene delivery
      using an Infiltrator in porcine coronary arteries to know the pattern of gene
      expression, efficacy and procedural complications. Twenty four coronary arteries
      in 13 pigs were used for intravascular gene delivery by intramural injection with
      either AdTbeta-ExR or adenovirus expressing beta-galactosidase (AdCALacZ). Direct
      immunofluorescent staining and reverse transcription polymerase chain reaction
      (RT-PCR) were used for detection of type II TGF-beta receptor and its mRNA
      respectively. X-Gal histochemistry was performed to identify beta-galactosidase.
      Both soluble TGF-beta receptor and beta-galactosidase were expressed locally in
      the media and adventita at injected arterial segments without any significant
      dissemination to remote area. Intravascular gene transfection performed with
      various titer of each adenoviral vector showed that AdTbeta-ExR of 5 x 10(8) pfu
      and AdCALacZ of 2.5 x 10(8) pfu were the minimum titer for the expression of each
      transgene. Infiltration of CD3 positive T cells was detected by
      immunohistochemical staining in the area of each transgene expression, and tends
      to decrease over time after gene delivery. Pathological study of 24 treated
      arteries showed complications such as disruption of external elastic lamina with
      hemorrhage (n = 4), minimal disruption of internal elastic lamina and endothelial
      layer, and medial thickening. In conclusion, catheter-based local intravascular
      gene delivery of adenoviral vector is feasible and effective in a selected
      artery, but must be undertaken with caution due to possible lethal complications.
      Local delivery of soluble TGF-beta type II receptor in this way may provide an
      effective intravascular gene therapy to inhibit TGF-beta signal pathway without
      any significant systemic side effect.

PMID- 12515397
TI  - Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial
      cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary
      damage by Vibrio vulnificus cytolysin.
AB  - Vibrio vulnificus cytolysin forms transmembrane pores that are permeable to
      calcium ions in pulmonary endothelial cells, and has been suggested as an
      important virulence factor that sequestrate neutrophils primarily in the lung. To
      elucidate the mechanism we investigated whether the cytolysin affect the
      expression of endothelial P-selectin and adhesiveness of pulmonary endothelial
      cells for neutrophils. The cytolysin increased the adhesiveness of CPAE cell, a
      pulmonary endothelial cell line, for neutrophils in a concentration- and time
      dependent manner. The increase of adhesiveness occurred within several minutes
      after the cytolysin exposure, persisted up to 90 min, and was not affected by
      cycloheximide. Furthermore, flow cytometric analyses showed that cytolysin
      enhanced the level of P-selectin on CPAE cell surface. Therefore, these results
      suggest that the cytolysin-induced hyperadhesiveness of pulmonary endothelial
      cells for neutrophils is mediated by the mobilization of endothelial P-selectin
      to the cell surface.

PMID- 12515398
TI  - Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from
      human genetic diseases by length and sequence dependent manner.
AB  - Trinucleotide repeat (TNR) instability can cause a variety of human genetic
      diseases including myotonic dystrophy and Huntington's disease. Recent genetic
      data show that instability of the CAG/CTG repeat DNA is dependent on its length
      and replication origin. In yeast, the RAD27 (human FEN-1 homologue) null mutant
      has a high expansion frequency at the TNR loci. We demonstrate here that FEN-1
      processes the 5'-flap DNA of CTG/CAG repeats, which is dependent on the length in
      vitro. FEN-1 protein can cleave the 5'-flap DNA containing triplet repeating
      sequence up to 21 repeats, but the activity decreases with increasing size of
      flap above 11 repeats. In addition, FEN-1 processing of 5'-flap DNA depends on
      sequence, which play a role in the replication origin-dependent TNR instability.
      Interestingly, FEN-1 can cleave the 5'-flap DNA of CTG repeats better than CAG
      repeats possibly through the flap-structure. Our biochemical data of FEN-1's
      activity with triplet repeat DNA clearly shows length dependence, and aids our
      understanding on the mechanism of TNR instability.

PMID- 12515399
TI  - Guideline for Hand Hygiene in Health-Care Settings: recommendations of the
      Healthcare Infection Control Practices Advisory Committee and the
      HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.
AB  - The Guideline for Hand Hygiene in Health-Care Settings provides health-care
      workers (HCWs) with a review of data regarding handwashing and hand antisepsis in
      health-care settings. In addition, it provides specific recommendations to
      promote improved hand-hygiene practices and reduce transmission of pathogenic
      microorganisms to patients and personnel in health-care settings. This report
      reviews studies published since the 1985 CDC guideline (Garner JS, Favero MS. CDC
      guideline for handwashing and hospital environmental control, 1985. Infect
      Control 1986;7:231-43) and the 1995 APIC guideline (Larson EL, APIC Guidelines
      Committee. APIC guideline for handwashing and hand antisepsis in health care
      settings. Am J Infect Control 1995;23:251-69) were issued and provides an in
      depth review of hand-hygiene practices of HCWs, levels of adherence of personnel
      to recommended handwashing practices, and factors adversely affecting adherence.
      New studies of the in vivo efficacy of alcohol-based hand rubs and the low
      incidence of dermatitis associated with their use are reviewed. Recent studies
      demonstrating the value of multidisciplinary hand-hygiene promotion programs and
      the potential role of alcohol-based hand rubs in improving hand-hygiene practices
      are summarized. Recommendations concerning related issues (e.g., the use of
      surgical hand antiseptics, hand lotions or creams, and wearing of artificial
      fingernails) are also included.

PMID- 12515400
TI  - Influenza: prospect for prevention and control.
AB  - Influenza is an emerging and re-emerging disease. Since the late 1930s influenza
      viruses have been isolated yearly from different parts of the world during
      epidemics and pandemics. The "epidemiologic success" of influenza is due largely
      to rapid and unpredictable antigenic changes (antigenic drift) among human
      influenza viruses, and the emergence of new subtypes (antigenic shift), mostly
      from reassortment between human and avian influenza viruses. Antigenic shifts
      were attributed to the global pandemic viruses of 1957 (H2N2 Asian flu) and 1968
      (H3N2 Hong Kong flu). Concern over possible new pandemics has been heightened by
      recent reports of human infection in Asia in 1997 with avian viruses (H5N1) and
      in 1999 (H9N2) and isolation of human-avian reassorted viruses from pigs and
      humans in Europe. Influenza has a high rate of inapparent infection, short
      incubation and high infectivity; epidemics usually start abruptly and spread
      rapidly to neighboring communities and countries. Isolation and quarantine are
      often unsuccessful in preventing the spread of the infection. Although not
      perfect, immunization and chemoprophylaxis are highly effective at minimizing the
      spread of influenza and reducing morbidity and mortality, social disruption and
      economic loss. Plans for future influenza epidemics and pandemics require
      national and international programs to be in place for the monitoring of
      influenza activity, the dissemination and exchange of information and the
      provision and delivery of sufficient quantities of vaccines and antiviral agents.
      This paper reviews and discusses the antigenic variations of the influenza virus,
      potential influenza pandemics, protective efficacy of inactivated vaccines and
      antiviral agents and preparation for control of future epidemics and pandemics.

PMID- 12515401
TI  - Possible mechanism of endothelin-induced Ca2+ mobility in A7r5 cultured vascular
      smooth muscle cells.
AB  - We studied the mechanism by which endothelin-1 (ET-1) affects the mobility of
      intracellular free Ca2+ ([Ca2+]i) in cultured A7r5 aortic smooth muscle cells. ET
      1 at 10(-9) to 10(-7) M increased [Ca2+]i in Ca2+-containing buffer and Ca2+-free
      buffer. Pretreatment with ET-1 inhibited thapsigargin- and carbonylcyanide m
      chlorophenylhydrazone (CCCP)-induced [Ca2+]i increases in Ca2+-free buffer.
      Pretreatment with thapsigargin and CCCP partially abolished the [Ca2+]i increase
      induced by ET-1. The ET-1-induced Ca2+ signal was partially suppressed by the ETA
      receptor antagonist BQ123 and the ETB receptor antagonist BQ788 and nifedipine.
      Pretreatment of cells with the phospholipase C inhibitor U73122 reduced the ET-1
      induced [Ca2+]i increase. These results suggest that the ET-1-induced [Ca2+]i
      increase in A7r5 smooth muscle cells initially activates the ETA receptor,
      leading to Ca2+ influx and increased internal Ca2+ release from endoplasmic
      reticulum and mitochondrial Ca2+ stores. The ETB receptor and L-type Ca2+ channel
      are involved in maintaining further extracellular Ca2+ influx. ET-1-induced
      intracellular Ca2+ release was also modulated by phospholipase C-coupled events.

PMID- 12515402
TI  - Clinical and urographic presentation of transitional cell carcinoma of the ureter
      in a blackfoot disease endemic area in southern Taiwan.
AB  - We reviewed the clinical, radiographic, and pathologic findings of ureteral
      transitional cell carcinoma (TCC) in a blackfoot disease (BFD) endemic area in
      southern Taiwan to increase understanding of tumor behavior in this area, which
      has a high incidence of urothelium carcinoma. From August 1995 to February 2002,
      28 histologically proven ureteral TCCs from this area were eligible for study.
      There was an unusual female predominance (male:female ratio, 1:1.333). The
      urographic filling defects in the 28 ureteral TCCs were classified into four
      categories. An ovoid filling defect was significantly associated with non
      invasive tumors (p = 0.003) and a trend toward low tumor grades (p = 0.073). The
      risk of ureteral TCC in this BFD endemic area of southern Taiwan remained high
      between August 1995 and February 2002. Urographic surveillance provides a simple,
      clear, inexpensive method to study the extent, location, and morphology of the
      ureteral mass. Detailed assessment of the image could be useful for preoperative
      planning and predicting prognosis. Large-scale, randomized, prospective clinical
      trials are needed to validate our results.

PMID- 12515403
TI  - Adrenal tumors: 10-year experience at Kaohsiung Medical University Hospital and
      literature review.
AB  - We report our 10-year experience of managing adrenal tumors at Kaohsiung Medical
      University Hospital (KMUH) between January 1992 and January 2002. In total, 53
      patients with adrenal tumors were analyzed, including 19 men (mean age +/-
      standard deviation, SD, 41.8 +/- 12.9 yr; range, 24-66 yr) and 34 women (mean age
      +/- SD, 42.3 +/- 12.4 yr; range, 19-74 yr), with an overall mean age +/- SD of
      42.6 +/- 12.5 years. All 53 adrenal tumors were confirmed by surgery and
      pathology. In our series, 41 (77.4%) tumors were functional, of which 39 (95%)
      were benign; 12 (22.6%) tumors were nonfunctional, of which two (16.7%) were
      malignant. Overall, women were more common than men in our series, especially in
      Cushing's syndrome and primary aldosteronism (female:male ratio, 4 and 1.9,
      respectively). Of the 41 functional adrenal tumors, 20 were primary
      aldosteronism, 10 were Cushing's syndrome, 10 were pheochromocytoma, and one was
      an androgen-producing tumor. Of the 12 nonfunctional adrenal tumors, all of which
      presented as adrenal incidentalomas, four were cortical adenoma, three were
      myelolipoma, two were ganglioneuroma, one was an adrenal cyst, one was an
      adrenocortical carcinoma, and one was a metastatic carcinoma. Overall, 48
      patients underwent adrenalectomy, three underwent partial adrenalectomy for small
      and well-circumscribed tumors, and two were explored. The diagnosis and
      management of adrenal tumors is discussed and the literature reviewed.

PMID- 12515404
TI  - Salvage procedures for failed compression hip screw fixation of intertrochanteric
      femoral fractures: analysis of 50 cases.
AB  - We retrospectively studied 50 patients who underwent salvage procedures for
      failed compression hip screw (CHS) fixation of intertrochanteric fractures from
      January 1991 to July 2000. Among these patients, seven underwent revision fixed
      angle plate surgery; 16 patients underwent bipolar hemiarthroplasty; five
      patients underwent Austin-Moore hemiarthroplasty; another nine patients underwent
      total hip arthroplasty; and 13 patients underwent removal of the implant. The
      age, gender, type of falling accident, osteoporosis status and post-operative
      ambulation status were recorded. The incidence of failed fixation of CHS was
      estimated at around 9.7%. A fall was recorded in 52% of cases. There was a
      significant difference in osteoporosis grade between the failed and successful
      CHS groups (p < 0.005). There was also better postoperative ambulation in the
      total hip replacement group compared to the other groups (p = 0.03). Surgical
      management of nonhealed intertrochanteric fractures is a challenge to orthopedic
      surgeons. The authors suggest multiple factors, such as fracture geometry, bone
      quality, preservation of acetabulum cartilage and individual patient factors, be
      considered when performing salvage procedures for failed CHS.

PMID- 12515405
TI  - Bile duct cancer 25 years after choledochoduodenostomy: a case report.
AB  - We describe a 65-year-old man who had undergone choledochoduodenostomy (CDS) for
      choledocholithiasis 25 years prior to admission to our hospital for cholangitis.
      Abdominal sonography and computerized tomography (CT) scan revealed a tumor mass
      at the hilar region with bilateral intrahepatic duct dilatation. Upper
      gastrointestinal endoscopic examination indicated the site of the CDS. Biopsy was
      taken from the mucosa of the bile duct, and pathology revealed well
      differentiated adenocarcinoma. CT scan and angiography further confirmed
      unresectable hilar bile duct cancer. Conservative treatment with intra-arterial
      chemotherapy was arranged. After briefly reviewing the hypothesized pathogenesis
      and radiographic diagnosis of this rare case, we recommend that chronic
      cholangitis consequent to CDS should be closely followed for late development of
      biliary tract malignancy.

PMID- 12515406
TI  - Snare-assisted transcatheter coil occlusion of patent ductus arteriosus.
AB  - Transcatheter occlusion of a small or moderate patent ductus arteriosus (PDA)
      using Gianturco coils is safe and effective. Several investigators have reported
      using different techniques with variable results. To eliminate the serious
      potential complications of inadvertent coil embolization to undesirable sites and
      to improve control of the coil throughout the procedure, a modified snare
      assisted method with approach from the main pulmonary artery was developed.
      However, articles discussing this technique are still limited. Herein, we report
      our successful experience of the snare-assisted technique to occlude small or
      moderate PDAs in three children aged from 1 to 8 years old. We achieved immediate
      total occlusion in all three cases with no complications. All three patients were
      discharged the next day and there was no coil dislodgement, left pulmonary
      stenosis, or residual shunting during the follow-up period of up to 3 years. This
      technique had the advantages of safety, optimal positioning, and improved
      stability of coil implantation.

PMID- 12515407
TI  - Hand-assisted laparoscopic live donor nephrectomy: a case report.
AB  - Live donor renal transplantation offers significant advantages over cadaveric
      renal transplantation. It yields significantly better patient and graft survival
      on both short-term and long-term follow-up. Laparoscopic donor nephrectomy
      minimizes the morbidities associated with the surgical procedure and allows a
      speedy return to normal daily activities. The operation also provides an
      atraumatic kidney subjected to minimal warm ischemia time and with adequate
      length of artery and vein, resulting in immediate functioning of the kidney after
      transplantation with a low rate of ureteral complications. A 37-year-old man was
      referred as a kidney donor for his brother. Both donor and recipient were
      hepatitis-B surface antigen carriers. Cross-matching and human leukocyte antigen
      test showed good compatibility. Left donor nephrectomy was performed successfully
      by hand-assisted laparoscopy. The warm ischemic time was 4.5 minutes and the
      graft kidney functioned immediately after transplantation. The donor was
      discharged from the hospital on postoperative Day 3 with good recovery.

PMID- 12515408
TI  - Ptyalism gravidarum: an unpleasant reality.

PMID- 12515409
TI  - Determining competence in estimating energy needs.

PMID- 12515410
TI  - ADA promotes dietitian's role as a 'certified provider' of diabetes self
      management training under Medicare Part B.

PMID- 12515411
TI  - Dietetics professionals and women's health research at the National Institutes of
      Health.

PMID- 12515412
TI  - Stature prediction equations for elderly non-Hispanic white, non-Hispanic black,
      and Mexican-American persons developed from NHANES III data.
AB  - OBJECTIVE: To develop new, nationally representative equations to predict stature
      for racial/ethnic groups of the elderly population in the United States. DESIGN:
      Anthropometric data for stature, knee height, and sitting height for adults aged
      60 years or older were collected from a sample of persons in the third National
      Health and Nutrition Examination Survey (1988-1994), a national probability
      sample of the US population. SUBJECTS: A gender- and racial/ethnic-stratified
      sample of 4,750 persons from the US population (1,369 non-Hispanic white men,
      1,472 non-Hispanic white women, 474 non-Hispanic black men, 481 non-Hispanic
      black women, 497 Mexican-American men, 457 Mexican-American women) aged 60 years
      or older participated in this study. STATISTICAL ANALYSES: Sampling weights were
      used to adjust the individual data to account for unequal probabilities of
      selection, nonresponse, and coverage errors so that all individual data used in
      these analyses represented national probability estimates. Regression analysis
      was performed to predict stature in each gender and ethnic group, and the results
      were cross-validated. RESULTS: Stature prediction models using knee height and
      age and sitting height and age were evaluated for each gender and racial/ethnic
      group. The equations with knee height and age were selected on the basis of root
      mean square error and pure errors in cross-validation and on the accuracy and
      validity of measures of knee height over sitting height. Results of these
      regressions, including regression coefficients, standard errors of the
      coefficients, multiple correlation coefficients, root mean square error, and the
      standard error for the individual for the final equations, are presented.
      CONCLUSIONS: New stature prediction equations using knee height and age are
      presented for non-Hispanic white, non-Hispanic black and Mexican-American elderly
      persons from current nationally representative data. These equations should be
      applied when a measure of stature cannot be obtained, for example, for persons
      with amputations of the leg, or with spinal curvature or who are confined to bed.
      Predicted stature values are acceptable surrogates in nutritional indexes.

PMID- 12515413
TI  - Counseling and motivational videotapes increase duration of breast-feeding in
      African-American WIC participants who initiate breast-feeding.
AB  - OBJECTIVE: To evaluate the relative effects introducing motivational videotapes
      and/or peer counseling in Special Supplemental Nutrition Program for Women,
      Infants, and Children (WIC) clinics serving African-American women have on breast
      feeding duration. DESIGN: Experimental intervention study. Pregnant women were
      enrolled at or before 24 weeks gestation and were followed up until postpartum
      week 16. Women were interviewed at enrollment, 7 to 10 days, 8 weeks, and 16
      weeks postpartum. SUNJECTS/SETTING: One hundred fifteen African-American WIC
      participants who initiated breast-feeding and who had been enrolled in 1 of 4
      clinics. INTERVENTION: Two-by-two factorial design, in which 4 clinics were
      randomly assigned to receive either no intervention, a motivational video package
      intervention, a peer-counseling intervention, or both interventions. MAIN OUTCOME
      MEASURES: Breast-feeding duration in weeks and relative risk ratios for breast
      feeding cessation before 16 weeks postpartum. STATISTICAL ANALYSIS PERFORMED:
      Contingency table analysis, including chi2 tests and log-rank tests; multivariate
      analysis using Cox proportional hazards regression analysis. RESULTS: A higher
      proportion of women were breast-feeding at 8 and 16 weeks postpartum in the
      intervention clinics than in the control clinic. The proportion of women
      reporting breast-feeding declined at 8 and 16 weeks postpartum, but the rate of
      decline was slower in the 3 intervention clinics than in the control clinic.
      Being younger than 19 years of age or older than 25 years of age, having a male
      infant, and returning to work or school all negatively affected breastfeeding
      duration, whereas previous breast-feeding experience positively influenced breast
      feeding duration. APPLICATIONS/CONCLUSIONS: WIC-based peer counselor support and
      motivational videos can positively affect the duration of breast-feeding among
      African-American women. WIC nutritionists and other health professionals in
      contact with this population should expand their efforts toward promoting
      increased duration of breast-feeding.

PMID- 12515414
TI  - Iron and zinc status of women and men who followed cholesterol-lowering diets.
AB  - OBJECTIVE: To determine if men and women taught the National Cholesterol
      Education Program step 2 diet experienced diminished iron or zinc status after 2
      years of consuming the diet. DESIGN: Subjects attended 8 weeks of diet classes
      and followup counseling. Four-day food records, zinc protoporphyrin/ heme (ZPP/H,
      a measure of iron stores), hematocrit, and plasma zinc values were collected at
      baseline, 1 year, and 2 years. SUBJECTS: Participants in a study of the efficacy
      of the step 2 diet (213 men and 151 women) who had low-density lipoprotein
      cholesterol levels above the 75th percentile, and who were not taking lipid
      altering medication. STATISTICAL ANALYSES: Paired t tests to compare
      preintervention and postintervention test results. Two-sample t tests to compare
      gender, menopause status, and hormone-use groups. Analysis of variance was
      performed to compare plasma zinc levels among diet-adherence subgroups.
      Individual evaluation of outlying values and backward stepwise regression to
      determine the independent effects of variables were also completed. RESULTS: Mean
      dietary intake approached or exceeded step 2 guidelines. Density of iron intake
      increased. Density of zinc intake was unchanged, but mean intake was low. Mean
      ZPP/H and hematocrit did not change for premenopausal or postmenopausal women
      with or without supplemental hormones; men's values changed only slightly.
      Abnormal ZPP/H and hematocrit occurred sporadically. Mean plasma zinc levels did
      not differ from baseline for women, increased slightly for men, and did not
      differ by level of dietary adherence. No plasma zinc concentrations were below
      normal. APPLICATION: In this large-scale, 2-year prospective study of women and
      men, no adverse effects on intake or plasma indicators of iron and zinc were
      detected as a result of subjects being taught the NCEP step 2 diet.

PMID- 12515415
TI  - Lead consumption of 18- to 36-month-old children as determined from duplicate
      diet collections: nutrient intakes, blood lead levels, and effects on growth.
AB  - OBJECTIVE: To determine the amount of lead ingested in food by means of duplicate
      diet collections, nutrient intakes, and anthropometric measurements of young
      children. DESIGN: Once a month for a year, data were collected from 24-hour
      duplicate diets, hand wipes, a dust index, and anthropometric measurements.
      Quarterly, venous blood samples were obtained. Thermal ionization spectrometry by
      means of a lead-205 tracer was used to determine lead present in food, blood, and
      the hand wipes. A dust index was determined on the basis of observation of dust
      on surfaces in the home. Anthropometric measurements obtained were height,
      weight, head circumference, and mid-upper arm circumference. SUBJECTS/SETTING:
      Subjects were 21 children, aged 18 to 36 months, who resided in homes located in
      an urban area with potentially high lead levels. MAIN OUTCOMES MEASURED: Lead
      contamination in food and on hands, and blood lead values, were determined.
      STATISTICAL ANALYSIS PERFORMED: Pearson correlation coefficients were used to
      determine relationships between lead content in food, blood, and hand wipes and
      growth. Multiple regression analyses examined the effect of food types and dust
      lead on lead levels in food, and the effect of these variables on head
      circumference. RESULTS: Mean blood levels were 0.3089 +/- 0.1496 micromol/L; 12
      samples contained more than 0.4826 micromol/L. Total intake of lead from food was
      4.95 microg/day and ranged from 1.10 to -22.10 microg/day. More than a fourth of
      the diets collected exceeded 6.00 microg/day. Foods considered home prepared were
      moderately related to blood lead level, and the dust index and hand wipe lead
      levels were related to total food lead. Home-handled foods, canned foods, and
      hand-wipe lead were significant predictors of the lead content in food. A
      negative relationship was found between head circumference and blood lead level.
      APPLICATIONS: Level of lead in food was directly related to hand-wipe lead. This
      finding underscores the need for dietitians and other health professionals to
      stress the importance of cleanliness in environments that are potentially lead
      contaminated. Appropriate hand washing and surface cleaning should be emphasized
      when preparing and consuming food. The inverse relationship between head
      circumference and blood lead levels points to the need for additional studies to
      validate this finding while controlling for other extraneous variables.

PMID- 12515416
TI  - Food consumption patterns of elementary schoolchildren in New York City.
AB  - OBJECTIVE: To examine food consumption patterns and related characteristics of
      schoolchildren. DESIGN: A representative survey involving a household
      questionnaire and child interview to conduct a nonquantitative 24-hour dietary
      recall. Indexes were developed to score the diets based on the Food Guide Pyramid
      and 5 A Day for Better Health recommendations. SUBJECTS/SETTING: Six hundred
      ninety-three 2nd-grade students and 704 5th-grade students from public and
      private schools in New York City. STATISTICAL ANALYSES PERFORMED: Weighted means
      and gender-adjusted analysis of covariance models were used to account for a
      complex survey design in calculating variance estimates. RESULTS: Compared with a
      maximum of 50, the mean Food Guide Pyramid index score was 29.2 for 2nd-grade
      students and 30.4 for 5th-grade students. The mean 5 A Day consumption score was
      3.4 and 3.6 servings of fruits and vegetables daily for 2nd and 5th graders,
      respectively. Measures of food consumption were significantly related to
      socioeconomic status, race/ethnicity, skipping meals, and participating in school
      lunch for both grades, and with meal preparation for 5th graders.
      APPLICATIONS/CONCLUSIONS: The Food Guide Pyramid and 5 A Day recommendations
      provide guidelines for food selection beginning in childhood. Knowledge and
      skills training are needed to improve food consumption patterns as children
      consume foods away from home and as they take on greater responsibility for meal
      preparation and food selection.

PMID- 12515417
TI  - Chefs' attitudes toward healthful food preparation are more positive than their
      food science knowledge and practices.
AB  - OBJECTIVE: To determine if chefs' and student chefs' attitudes, knowledge, and
      practices regarding healthful food preparation are consistent with the Dietary
      Guidelines for Americans. DESIGN: An analytical survey questionnaire was
      distributed to 4 chef groups. Sections 1 and 2 of the survey measured chefs' food
      science knowledge (13 questions) and likelihood of using food preparation
      practices (15 questions) necessary to meet the 1990 Dietary Guidelines for
      Americans. Section 3 (22 questions) measured chefs' attitudes toward nutrition in
      general, toward the importance of healthful food preparation practices, and
      toward the US Dietary Guidelines. SAMPLE: Of 512 surveys distributed by mail, at
      culinary meetings, and in classes at 2 culinary schools, 447 (86%) were returned
      (158 from practicing chefs and 289 from student chefs). Practicing chefs included
      chef educators, foodservice chefs from a national corporation, and independent
      chef members of the American Culinary Federation of New York City. STATISTICAL
      ANALYSIS: Descriptive statistics included frequencies, means, and standard
      deviations of survey items and of individual survey sections. Reliability and
      validity were determined using alpha coefficients and principal components
      analysis. Analysis of variance was used to examine differences in practice,
      attitudes, and knowledge among chef groups. RESULTS: Both practicing chefs and
      student chefs answered more than 70% of the food science questions correctly;
      independent chefs scored significantly lower than educator and corporate chefs.
      More than two thirds of the chefs and student chefs correctly responded to
      questions about the nutrient composition of food and how cooking affects the
      nutrient content of food. All chef groups were confused about fat and cholesterol
      in food and in the body. Few healthful food preparation practices were likely to
      be used by any chef group more than two thirds of the time, although the subscale
      of the attitude toward the importance of these practices was very positive. The
      majority of practicing chefs thought that customers do not care about the US
      Dietary Guidelines and nutrition; student chefs thought that customers do care.
      Both groups strongly agreed that, as chefs, they are responsible for the
      nutritional content of the food they prepared. APPLICATION: Both chefs and
      student chefs are willing to learn about food science and recipe modification
      principles as they apply to healthful cooking practices. The opportunities are
      clear: Dietitians have the expertise to teach chefs healthful food preparation
      techniques, recipe modification, and food composition information.

PMID- 12515418
TI  - Nutritional concerns in American Indian and Alaska Native children: transitions
      and future directions.
AB  - The nutritional health of American Indian and Alaska Native children has changed
      dramatically over the past 30 years. The prevention and treatment of malnutrition
      (primarily undernutrition) was a major health issue until the mid to late 1970s.
      Now, a generation later, obesity in American Indian and Alaska Native children is
      a major health threat. In 1969, the National Institutes of Health sponsored a
      conference to review the nutritional status of North American Indian children and
      to set a national agenda to improve the nutritional health of Indian children.
      Subsequently, increased food availability; food assistance programs; and improved
      sanitation, transportation, and health care have eliminated undernutrition as a
      major health issue. However, the substantial reduction in undernutrition has been
      accompanied by a rapid increase in childhood obesity. The current epidemic of
      child and adult obesity and associated obesity-related morbidities, such as type
      2 diabetes mellitus and other chronic diseases, has implications for the
      immediate and long-term health of young American Indians. This article reviews
      the current nutritional health of American Indian and Alaska Native children, the
      changes that have occurred the past 30 years, and the nutrition transition to
      increasing obesity and subsequent diabetes that is being seen in American
      Indians. Future directions to improve the health of American Indian and Alaska
      Native children are discussed, as is the urgent need for obesity prevention
      programs that are culturally oriented, family centered, and community- and school
      based and that target healthful eating and physical activity beginning in
      childhood.

PMID- 12515419
TI  - Patient-focused care and its implications for nutrition practice.
AB  - Patient-focused care is a central element in work redesign and restructuring of
      health-care delivery systems. It affects all levels of dietetics practice.
      Patient-focused care poses potential benefits and challenges for nutrition
      professionals, including opportunities to expand the scope of practice and to
      share traditional nutrition duties with others. This article provides a brief
      overview of the basic components and terms of patient-focused care and reviews a
      case study that illustrates how implementation of patient-focused care in a
      community hospital has influenced the hospital's organizational structure and
      delivery of nutrition care and services. A review of the initial goals of patient
      focused care in relation to long-term outcomes provides perspective for those
      beginning or in the midst of the reengineering process.

PMID- 12515420
TI  - Nutrition and oral health guidelines for pregnant women, infants, and children.
AB  - Good oral health care and nutrition during pregnancy, infancy, and childhood are
      essential but often overlooked factors in the growth and development of the teeth
      and oral cavity. Pregnant women and parents and caregivers of infants and
      children often receive little guidance about proper preventive dental and oral
      health care, including fluoride and dietary measures. Pregnant women can maintain
      their health through proper diet, good oral hygiene, and appropriate use of
      fluoride. An adequate diet during gestation is important for optimal oral
      development of the fetus. To promote good oral health in infancy, caregivers need
      to provide the infant with appropriate amounts of fluoride in addition to a
      healthful diet. As the teeth erupt into the mouth, the caregiver needs to clean
      the teeth thoroughly on a daily basis. When solid foods are introduced in later
      infancy, it is also important to limit the frequency of caries-promoting
      fermentable carbohydrates between meals. Good oral hygiene habits and dietary
      practices that emphasize minimum exposure to retentive, fermentable
      carbohydrates; use of fluoridated water; and a varied, balanced diet should
      continue throughout childhood to set the stage for optimal oral health for a
      lifetime.

PMID- 12515421
TI  - Spreading the message of good oral health care for children.

PMID- 12515422
TI  - Paucity of nutrition and food safety 'news you can use' reveals opportunity for
      dietetics practitioners.
AB  - The media is consistently ranked by the public as their primary source of
      nutrition and food information. To address the question of what the public is
      hearing about food, nutrition, and health through the news media, the
      International Food Information Council Foundation commissioned the Center for
      Media and Public Affairs to conduct a content analysis of nutrition and food
      safety stories. The study examined media coverage from 53 print and electronic
      news outlets during a 3-month period from May through July 1995. Specific
      criteria were applied to select the sample of food and nutrition stories (n =
      979) by length of coverage during the reporting period. Coverage related to food
      policy or regulation, food programs, individual food companies or products,
      advertising or marketing, and economic adulteration or tampering were excluded
      from the sample. The analysis of media coverage of food and nutrition topics
      revealed a twofold emphasis on dietary fat over other topics. Consumption of
      dietary fat was mentioned in almost half of all reports, apart from discussions
      of body fat, weight, or obesity as a health issue. The content analysis also
      showed an inverse relationship between media stories of foods by food group
      compared with the recommended number of servings in the Food Guide Pyramid.
      During an era in which Americans receive their health, nutrition, and food
      messages from the media rather than from health professionals such as physicians
      and dietitians, there are multiple challenges for communicating with the public.
      Our media research and its findings offer approaches for dietetics practitioners
      to use when providing nutrition and food recommendations and education for
      clients and the public. These include communicating science, providing context,
      reinforcing basic messages and guidelines, and promoting action and behavior
      change to clients and consumers.

PMID- 12515423
TI  - Plasma carotenoids as biomarkers of fruit and vegetable servings in women.

PMID- 12515424
TI  - Awareness of the link between bone disease and calcium intake is associated with
      higher dietary calcium intake in women aged 50 years and older: results of the
      1991 CSFII-DHKS. Continuing Survey of the Food Intake of Individuals. Diet and
      Health Knowledge Survey.

PMID- 12515425
TI  - Reducing barriers to participation in weight-loss programs in low-income women.

PMID- 12515426
TI  - Position of the American Dietetic Association: liberalized diets for older adults
      in long-term care.
AB  - Malnutrition, weight loss, and resident satisfaction are serious issues that need
      to be addressed by dietetics professionals working in long-term-care facilities.
      Medical nutrition therapy for older adults in long-term care is multifaceted and
      critical to reducing the risks of malnutrition and weight loss. To meet the needs
      of every resident, dietetics professionals must consider each person
      holistically, including personal goals, overall prognoses, benefits and risks of
      treatment, and perhaps most important, quality of life. For some long-term-care
      residents the use of liberalized diets, when appropriate, can enhance both
      quality of life and nutritional status, thus increasing the resident's
      satisfaction with the meals provided and reducing the risks of malnutrition and
      weight loss.

PMID- 12515427
TI  - Position of the American Dietetic Association: the role of nutrition in health
      promotion and disease prevention programs.
AB  - A healthful diet and wise food choices are critical components of promoting
      health and reducing the risk of chronic disease. A substantial amount of health
      care resources could be saved by expanding health promotion and disease
      prevention programs that target dietary change among Americans. To effectively
      reduce health care costs, the emphasis and delivery of health care must promote
      health as well as deliver treatment and rehabilitative services to the sick.
      Prevention measures, such as nutrition interventions that also encourage physical
      activity, can help prevent or halt progression of full-blown chronic disease and
      thus decrease chronic disease disability. Health promotion and disease prevention
      need to be integral parts of all health care, community, public health, and
      worksite programs across the life cycle. Correspondingly, such programs must be
      culturally competent and address the specific needs of vulnerable or underserved
      populations. Dietetics professionals in all areas of practice should play an
      integral role in health promotion and disease prevention programs. Achieving this
      goal will require expansion of training programs and active learning by dietetics
      professionals that includes theory and practice in using team approaches,
      developing coalitions, and managing complex systems. Dietetics professionals also
      need to amplify their understanding of politics, administration, health care
      financing, and reimbursement. Attention must also be expanded to include social
      and behavioral sciences and to address program evaluation, outcomes, and cost
      benefit and cost-effectiveness in nutrition-focused health promotion and disease
      prevention programs. Continued training in program development, research, and
      evaluation will help build the body of evidence that supports ongoing inclusion
      of prevention in a rapidly changing health care environment.

PMID- 12515428
TI  - President's page: staying attuned to consumer needs.

PMID- 12515429
TI  - Quantitative neuropathological analysis of sudden infant death syndrome.
AB  - Detailed stereological analyses of specific regions of brains of children who had
      died from Sudden Infant Death Syndrome (SIDS) was undertaken to determine whether
      global evidence of an underlying pathology exists, contributing to an increased
      susceptibility to SIDS. A significant reduction in the total number of
      neocortical neurones and neurone volume was observed in SIDS normal birth weight
      (NBW) infants in comparison to controls. A significant reduction in both volume
      and total neurone number were also noted in the dorsal motor nucleus of the vagus
      in SIDS NBW group when compared with controls. Anomalies in regions of the brain
      involved with cardiorespiratory control (brainstem) and arousal (brainstem and
      neocortex) may play a crucial role in the chain of events resulting in a SIDS
      event.

PMID- 12515430
TI  - Assessment of infant physiology and neuronal development using magnetic resonance
      imaging.
AB  - Previous work has demonstrated both that there are substantial individual
      differences in the rate of physiological development,and that infants with risk
      factors for Sudden Infant Death Syndrome (SIDS) develop more slowly, suggesting
      that their increased vulnerability may be due to delayed neuronal development
      associated with compromised development in fetal or early neonatal life. This
      project aims to test the hypothesis that individual differences in the rate of
      physiological development of infants correlate with measurable differences in the
      rate of brain development as assessed by magnetic resonance imaging (MRI). Sixty
      infants were recruited to this study in three different groups that are known to
      have differing rates of physiological development. MRI was performed successfully
      in 49 cases at 6 weeks of age without sedation. Forty-one of these cases had full
      follow-up (15 normal; 19 IUGR; 11 'high risk'). Postnatal physiological
      development was assessed by measuring age-related deep body temperature patterns
      during sleep. Neuronal development was assessed by subjective analysis of MRI
      images and objective measurements relating to myelination using T1 and diffusion
      weighted (23 cases) MRI images. As expected the normal group acquired the adult
      temperature pattern earlier, but this was not statistically significant. All MRI
      scan appearances were within normal limits. Ranking cases subjectively in order
      of maturity revealed no significant pattern. The normal group had a significantly
      higher myelination score than the IUGR and 'high risk' groups (P = 0.001). This
      trend was also shown by the diffusion weighted myelination score but did not
      reach statistical significance. No significant differences were seen in both the
      subjective and objective MRI measurements and development of nocturnal
      temperature patterns. The results suggest there may be differences in
      neurodevelopment between the different groups at 6 weeks of age but these are not
      linked to late development of temperature patterns. It is therefore unlikely that
      this related to a global delay in maturation.

PMID- 12515431
TI  - Antenatal inflammation and infection in chronic lung disease of prematurity.
AB  - In spite of improved neonatal care, chronic lung disease of prematurity (CLD)
      remains a major cause of morbidity and mortality in extremely preterm infants.
      Our current understanding is that antenatal infection can trigger intra-uterine
      inflammation which then promotes preterm labour. Recent studies suggest that
      antenatal infection and inflammation can also increase the preterm infant's
      susceptibility to develop CLD. It may be that exposure of the fetal lung to high
      concentrations of pro-inflammatory cytokines is the cause of this increased
      susceptibility. One candidate for initiating intra-uterine inflammation is
      ascending infection by the vaginal commensal Ureaplasma urealyticum (Uu).
      Antibiotics administered to mothers prior to delivery appear to improve the
      neonatal outcome in cases of preterm prolonged rupture of membranes, but not in
      cases of preterm labour with intact membranes. Uu can be transmitted vertically
      to the airways of the preterm infant, but the role of Uu in causing CLD remains
      uncertain. Small trials of antibiotics given to preterm infants after delivery
      have not shown any consistent benefit in reducing CLD. Although CLD remains a
      significant problem for the extremely preterm infant, it is likely that molecular
      biology techniques, such as the polymerase chain reaction, will enhance the
      detection of antenatal infection and further our understanding of the
      pathogenesis of CLD.

PMID- 12515432
TI  - Sleeping O2 saturation levels in infants.
AB  - Longitudinal recording of O2 saturation during night-time sleep of 82 infants
      show significantly more falls below 93% in females and infants of mothers who
      smoke. Implications are discussed.

PMID- 12515433
TI  - Patterns of symptoms in siblings of sudden infant death syndrome infants.
AB  - Longitudinal day-to-day recordings of symptoms in the siblings of Sudden Infant
      Death Syndrome (SIDS) infant show a wide variety of symptoms varying with season
      and days of years. Implications are discussed.

PMID- 12515434
TI  - Why is smoking a risk factor for sudden infant death syndrome?
AB  - Smoking is a major risk factor for both Sudden Infant Death Syndrome (SIDS) and
      respiratory tract infections. Such infections, both viral and bacterial, also
      increase the SIDS risk. This study investigated the effect of cigarette smoke at
      two stages of infection: 1) mucosal surface colonization; 2) induction and
      control of inflammatory responses. For colonization, RSV or influenza A infected
      cells bound several bacterial species in significantly higher numbers due to
      increased expression of host cell antigens. Buccal epithelial cells from smokers
      bound significantly more bacteria. For Staphylococcus aureus, this was associated
      with increased tar levels. Some SIDS deaths have been proposed to result from
      high levels of pro-inflammatory mediators elicited by infection and/or cigarette
      smoke during a developmental period when infants are less able to control
      inflammatory responses. Inflammatory reponses were compared between blood samples
      from smokers (n = 42) and non-smokers (n = 60) stimulated with TSST-1 or LPS. Non
      smokers had significantly higher IL-6 (P = 0.011), IFN (P = 0.003) and IL-10 (P =
      0.000) baseline levels. Non-smokers had higher IFN (P = 0.008) and IL-1 (P =
      0.001, 0.007) responses to LPS and higher IL-10 responses to TSST-1 (P < 0.05)
      and LPS (P < 0.000). This study highlights that smoking increases the SIDS risk
      by greater susceptibility to viral and bacterial infections and enhanced
      bacterial binding after passive coating of mucosal surfaces with smoke
      components. In animal models, IL-10 reduced the lethal effect of staphylococcal
      toxins. In this study, smokers had lower IL-10 responses toTSST-1 and LPS. Dose
      response effects of cigarette smoke exposure needs to be established in relation
      to inflammatory response control and infantile infections.

PMID- 12515435
TI  - Evidence for a genetic component in sudden infant death syndrome.
AB  - There is increasing evidence that inflammatory responses have been elicited in
      some Sudden Infant Death Syndrome (SIDS) infants and that these responses are
      under genetic control. The objective of this study was to investigate the
      hypothesis that the cytokine responses of SIDS parents (n = 41) differed
      significantly from control donors (n = 61). Blood samples were stimulated with
      the staphylococcal toxin TSST-1 and LPS from Eschericia coli and assessed for
      production of TNF, IL-1, IL-6, IFN and IL-10. In response toTSST-1 (P < 0.02) and
      LPS (P < 0.002), SIDS parents produced higher levels of IL-1 than the controls.
      SIDS parents produced higher levels of IFN in response to TSST-1 compared to LPS
      (P < 0.001) although in response to LPS, the IFN (P = 0.0008) and IL-6 (P <
      0.0002) responses of the SIDS parents were lower than those of the controls. For
      TNF and IL-10, there was little difference between the two groups unless the
      effect of smoking was considered. As part of this work, a small pilot genotyping
      study was carried out using DNA from SIDS parents (n = 10), control donors (n =
      10) and Bangladeshi subjects (n = 10). An IFN polymorphism (3/3) was found in
      40%,15.4% and 0% of donors respectively. Staphylococcal toxins have been
      identified in SIDS infants therefore this study highlights the importance of
      assessing IL-1 levels. Determination of cytokine polymorphisms and consideration
      of interactions between these and environmental factors such as smoking in high,
      average and low risk ethnic groups will assist in establishing the contribution
      of these factors to an infant's susceptibility to SIDS.

PMID- 12515436
TI  - Hair-element analysis--still on the fringe.
AB  - Increasing biological interest in minerals has led to the search for reliable
      methods to quantify body levels of trace elements and toxic metals. Hair has been
      a prime candidate because of its ease of collection and the possibility that this
      body tissue might accurately reflect body loads of these substances. A vast
      amount of research effort has been expended to explore the value of hair-element
      analysis. Unfortunately, there are so many confounding factors that influence
      these measurements that isolated individual results cannot be relied upon. Their
      current value is in epidemiological studies.

PMID- 12515437
TI  - Central and peripheral temperature change in normal infants.
AB  - The purpose was to explore the relationship between the fall in rectal
      temperature seen in normal infants after being put down to sleep and the
      concomitant rise in peripheral shin temperature. In this observational study 21
      normal infants had continuous overnight peripheral shin and central rectal
      temperature recorded, for three nights at 2 weeks, 6 weeks, 3 months and 5 months
      of age. Parents documented the start and end of feed/nappy changing episodes
      during the night. All recordings were made in the infants' own home. A strong
      inverse linear correlation (median r2 = 0.95, lower quartile 0.92, upper quartile
      0.97) was seen between rectal temperature and shin temperature on falling to
      sleep when put down on 106 (65%) of 161 nights. On many other nights a
      significant nonlinear association was present. It was not possible to exclude the
      process of being put down to sleep as a confounding variable in this strong
      association. However, a similar inverse relationship between shin and rectal
      temperature was seen overnight during 111 of 121 (92%) feed/nappy changing
      episodes. If causal, the development in early infancy of an inverse relationship
      between shin and rectal temperature may be important for cardiovascular
      homeostasis. Further sleep laboratory work including video recording is required
      to separate the peripheral and central temperature changes that take place on
      falling to sleep from those associated with removal of clothing during a nappy
      change.

PMID- 12515438
TI  - Polymorphisms in genes involved in glucose metabolism in cases of sudden infant
      death syndrome.
AB  - BACKGROUND: Infants with intra-uterine growth retardation have an increased risk
      of Sudden Infant Death Syndrome (SIDS). Hypoglycaemia is also significantly
      correlated with retardation of intra-uterine growth. A number of mutations in key
      proteins involved in regulation of blood glucose (e.g. glucokinase) have been
      found to result in reduced birth weight. Heterozygous mutations in the coding
      region of the glucokinase gene have been shown to cause MODY (a form of early
      onset Type II diabetes mellitus). The aim was to screen a cohort of SIDS and
      control infants who were either growth retarded or appropriately grown for
      gestational age to determine if any mutations and/or polymorphisms were present
      in the glucokinase gene. METHODS: PCR, denaturing high performance liquid
      chromatography on an automated Transgenomic WAVE DNA fragment analysis system and
      DNA sequencing. RESULTS: Genomic DNA was isolated from 129 infants who were
      either growth retarded or appropriately grown for gestational age. We found
      several rare novel polymorphisms in the glucokinase gene in the infant samples.
      However, none of the samples contained any of the mutations in the glucokinase
      gene previously reported in cases of MODY. CONCLUSIONS: We have found rare novel
      polymorphisms in the glucokinase gene in the infant samples. In contrast in these
      samples, we have not found any examples of the previously reported mutations in
      the coding region of the glucokinase gene found in MODY. This clearly shows that
      while MODY babies are often small, MODY is not a common cause of either intra
      uterine growth retardation or of SIDS.

PMID- 12515439
TI  - Sudden infant death syndrome--a defect in circulatory control?
AB  - The majority of Sudden Infant Death Syndrome (SIDS) infants die during sleep and
      especially during the overnight sleep period. Recent evidence from SIDS cases,
      which occurred while on a cardiorespiratory monitor at home, has suggested that
      the mechanism of death involves circulatory failure, with the development of a
      shock like state, associated with a progressive bradycardia in the presence of
      continued breathing movements. In this paper we explore the circulatory effects
      of sleep and in particular the down regulation of the baroreceptor reflex,
      associated with a reduction in vasomotor tone and a fall in central venous
      return, cardiac output and blood pressure. This sequence of events would be
      exacerbated by many of the known SIDS risk factors, namely the prone sleeping
      position, overheating and co-sleeping. Poor central venous return,with diminished
      cardic distension could induce a progressive bradycardia as occurs in adults with
      neuro-cardiogenic syncope. Alternatively a reduced cardiac output could result in
      the rapid onset of severe hypoxia through poor lung perfusion. The effects of
      sleep on circulatory control deserve further study in infants.

PMID- 12515440
TI  - Developmental disorders of glucose metabolism in infants.
AB  - BACKGROUND: Developmental failures to adequately control postnatal blood glucose
      levels are common in the transition from fetal to infant life and can persist for
      many months. The standard method of functionally measuring hepatic glucose
      production and/or disordered glucose production is the response to a glucagon
      tolerance test. METHOD: We adapted the standard glucagon tolerance test used for
      children and adults for use in preterm infants. 79 consecutive preterm infants
      gestational age range 25-36 weeks (mean 32.2 weeks), mean birth weight 1.66 kg
      admitted to the Neonatal Intensive Care Unit, Ninewells Hospital, Dundee and who
      survived to discharge home were recruited into the study. At the time of
      discharge home the characteristics of the group were as follows: adjusted mean
      gestational age 36.7 weeks, mean discharge weight 2.23 kg. RESULTS: In this study
      of preterm infants the maximal increase in plasma glucose following
      administration of a glucagon tolerance test is 1.39 +/- 07 mmol/L, n = 78 (range
      0-3.98 mmol/L). CONCLUSIONS: An increase in plasma glucose of less than 4 mmol/L
      is considered abnormal in adults following administration of a fasting glucagon
      tolerance test. The responses of preterm infants and adults to glucagon are
      clearly different. The attenuated response to glucagon in the preterm infants is
      consistent with the low levels of hepatic glucose-6-phosphatase activity in
      premature infants as glucose-6-phosphatase is the terminal step of the two main
      pathways of liver glucose production.

PMID- 12515441
TI  - Epidemiological investigation of sudden infant death syndrome infants-
      recommendations for future studies.
AB  - In recent years the study of infant care practices within the sleeping
      environment has proved to be the single most important set of observations for
      reducing the risk of Sudden Infant Death Syndrome (SIDS). To further reduce the
      number of deaths and resolve the debate on safe infant care practice, a closer
      scrutiny of this environment is required. However, anecdotal observation from
      uncontrolled death-scene investigations and a reluctance to diagnose SIDS because
      of adverse social conditions or circumstantial evidence at the time of death is
      undermining future research. To investigate SIDS now means investigating the
      wider umbrella of all Sudden Unexpected Deaths in Infancy (SUDI) because of the
      potential for misdiagnosis. In trying to find out why SIDS infants die we have
      increasingly been forced to search for why infants survive in the first few
      months of life and it is this comparative component of epidemiological
      observation that has saved so many lives. A death-scene investigation is vital to
      any planned future investigation of SIDS but equally essential is a sleep-scene
      investigation of surviving infants to put any findings into context. SIDS infants
      are no longer scattered across the social strata and the cot is not the only
      environment in which they are found, social deprivation and use of the parental
      bed are now more discernable. Future studies should therefore reflect these
      changes with a second control group of surviving infants more closely matched to
      the type of environment in which SIDS infants might be found.

PMID- 12515442
TI  - Triadic bed-sharing and infant temperature.
AB  - The effects on infants of sleeping with their parents is currently the subject of
      much debate. One concern regarding infants who sleep in their parents' bed
      involves the possibility of overheating. Previous research reported a
      significantly greater core temperature of 0.1 degrees C among a cohort of bed
      sharing infants compared with a matched cohort of infants sleeping alone. This
      paper presents a preliminary analysis of the overnight rectal temperature of 12
      of the 20 infants who were monitored sleeping alone and with their parents on
      separate nights at the University of Durham Parent-Infant Sleep Lab. No
      significant differences were found in all night rectal temperature, or
      temperature from 2 h after sleep onset between bed-sharing and cot sleeping
      nights. These preliminary analyses suggest a night-time difference in rectal
      temperature between routine bed-sharers and routine cot sleepers, however, these
      findings will be further explored in the full analyses for this study.

PMID- 12515443
TI  - Deep body temperature changes in twins.
AB  - Twins show differences in physiological maturity within and between twin sets;
      where one infant is 5-weeks later than its sibling; while one pair may both be
      slow but develop together. Zygosity, birth weight and sex may be contributory but
      not causative factors. How vulnerability to illness may be affected, is
      discussed.

PMID- 12515444
TI  - Predicting outcome in acute stroke: a comparison between QEEG and the Canadian
      Neurological Scale.
AB  - OBJECTIVE: To determine and compare the predictive value of quantitative EEG
      (QEEG) and the Canadian Neurological Scale (CaNS), in patients with an acute
      cerebral stroke. METHODOLOGY: Twenty-eight patients were studied with the
      diagnosis of acute ischemic middle cerebral artery stroke, within the first 72
      hours of clinical evolution. Thirty-seven EEGs and clinical evaluations were
      collected: 13 during the first 24 hours after stroke onset, 9 between 24-48 hours
      and 15 between 48-72 hours. The QEEG studied variables were: the Z values
      (maximum, minimum and the Z medians from the 5 nearest points to each one) of
      absolute energies (AE) from the 4 classic frequencies bands. The clinical scale
      showed a smaller percent of correct prognosis than QEEG variables. CONCLUSIONS:
      QEEG was demonstrated to be a powerful tool to predict the degree of residual
      functional disabilities after an acute ischemic stroke and showed a higher
      prognostic value than CaNS when they are performed within the first 72 hours of
      brain infarct.

PMID- 12515445
TI  - Electrophysiology of the frontal lobe.
AB  - The electrophysiology of the frontal lobe appears to be unimpressive when the
      view is limited to the routine EEG recording of a healthy waking adult. There is
      usually low voltage fast activity, which becomes more pronounced when recorded
      with depth leads. Three special EEG patterns of marginal to slightly abnormal
      character are discussed: a) rhythmical midfrontal 6-7/sec activity of juveniles,
      b) rhythmical midfrontal sharp 4-6/sec activity of infancy and early childhood
      with arousal from sleep, and c) frontal intermittent rhythmical delta activity
      (FIRDA) in waking adults with frontopolar maximum, possibly related to thought
      processes under abnormal conditions. With extension of the frequency range,
      ultraslow (DC-like) as well as fast beta (gamma, 40-80/sec) and ultrafast
      activity (80-1000/sec) are found particularly over the frontal lobes. Ultraslow
      baseline shifts are arousal-related and mixed with overlying ultrafast waves.
      Attention control and the "working memory" involve chiefly the dorsolateral
      prefrontal cortex, investigated with P300 responses and likely to show ultrafast
      spectra. Perception-related 40-80/sec gamma activity has been thought to be
      associated with the entrance into consciousness. Initiation and design of motor
      activity spreads from prefrontal to the frontomotor cortex, associated with
      powerful event-related potentials: contingent negative variation (CNV) and
      "Bereitschafts potential" ("readiness potential," RP). Neuroscientific research
      of the highest frontal lobe functions has become a very active domain of
      neuroimaging. With the use of the extended frequency range, EEG and also evoked
      potential studies could add further information with acquisition in real time.
      Ultrafast frequency ranges presented in computerized frequency analysis and
      mapping might show impressive correlates of highest frontal lobe functions.

PMID- 12515446
TI  - The frontal arousal rhythm (FAR) is an ictal pattern: a case report.
AB  - This paper deals with a patient with the Frontal Arousal Rhythm (FAR), a rare
      rhythmic pattern usually seen in young children awakening from sleep, with a
      history of seizures. In this patient, subtle clinical changes were observed on
      the video during the pattern, consisting of a sequence of brief eye lid flutter,
      chewing, increased inspiration and upper lip quivering. This exact sequence was
      seen on three successive occasions lasting for 6,9, and 10 sec. The conclusion is
      the FAR is not just a sign of seizure disorder, but is actually an ictal pattern.

PMID- 12515447
TI  - Benign neonatal sleep myoclonus: case report and follow-up of four members of an
      affected family.
AB  - Benign neonatal sleep myoclonus (BNSM), characterized by myoclonic jerks of the
      extremities only in non-REM sleep, occurs in the first months of life with
      spontaneous disappearance within 3-4 months. We examined five siblings with
      typical BNSM, at the 3-10 years follow-up neurological examination. Psychomotor
      development, cognitive functions and EEG were completely normal. These cases
      confirm that BNSM is a self limited and nonepileptic disorder.

PMID- 12515448
TI  - Sleep disorders in Sanfilippo syndrome: a polygraphic study.
AB  - OBJECTIVE: A high prevalence of sleep disorders is reported in patients affected
      by Mucopolysaccharidosis III (Sanfilippo syndrome). These disorders have never
      been investigated by prolonged, objective, and instrumental evaluations. The
      present work is based on sleep duration and structure in Sanfilippo patients.
      STUDY DESIGN: The features of sleep/wake cycle in 6 Sanfilippo patients and 6
      healthy controls were evaluated by means of sleep diaries and 48 hour ambulatory
      EEG and polygraphic recordings. Statistical analysis was performed by means of
      the U-test (Mann-Whitney). RESULTS: Four out of six Sanfilippo patients, the
      oldest patients in our sample, showed an extremely irregular sleep pattern, with
      several sleep episodes of inconstant duration, irregularly distributed along 24
      hours. The two younger patients showed sleep maintenance insomnia with several
      nocturnal awakenings. CONCLUSIONS: These results suggest that sleep disruption in
      Sanfilippo syndrome consists of an irregular sleep/wake pattern, which at its
      onset might appear as a disorder of initiating or maintaining sleep. This could
      explain why same patients do not respond to conventional hypnotics. The present
      observation might suggest attempting therapies aimed at resynchronization, such
      as behavioral treatment, light therapy or melatonin.

PMID- 12515449
TI  - Spikes immediately after electroconvulsive therapy in psychotic patients.
AB  - The goal of this study was to assess the spikes systematically and to clarify an
      epileptc abnormality induced by electroconvulsive therapy (ECT). Our subjects
      were 20 psychotic patients with no spikes on prior EEGs. ECT was performed by
      applying electrical current to both sides of the patient's temple every 2 or 3
      days for a period of between 1-4 weeks. The first EEG examination was performed
      either on the day that the ECT course was completed or on the following day.
      Subsequent EEG examinations were performed at intervals of 2 or 3 days. Thirteen
      of the 20 patients showed spikes. There were no significant differences in age,
      gender, diagnosis, or type of ECT. Patients with spikes had significantly more
      ECT sessions than those without spikes. The spikes were present in the frontal,
      temporal and central areas, predominantly frontal, anterior temporal and mid
      temporal region, and almost disappeared in 1-3 weeks. The occurrence of spikes
      immediately after ECT was demonstrated. Although this abnormality was transient,
      it could indicate that in humans ECT causes the early stage of kindling
      phenomenon as a result of repeated application, and that the temporal lobe seems
      to play a major role in order to induce the phenomenon.

PMID- 12515450
TI  - Lithium intoxication mimicking clinical and electrographic features of status
      epilepticus: a case report and review of the literature.
AB  - A 58-year-old patient who was somnolent, distractible and confused is presented.
      She was previously treated with lithium, and a plasma level was mildly elevated
      at 1.7 mmol/l (normal 0.5-1.5 mmol/l). The EEG was suggestive of electrographic
      status epilepticus. Following treatment with i.v. lorazepam, neither mental
      status nor EEG abnormalities improved. She had a full recovery of mental function
      and markedly improved EEG findings following discontinuation of lithium. The EEG
      is an effective tool for diagnosing lithium neurotoxicity in patients with normal
      or mildly elevated lithium plasma levels. However, caution is needed before
      making an assumption of status epilepticus.

PMID- 12515451
TI  - Epileptic nystagmus and its possible relationship with PGO spikes.
AB  - A simultaneous video-EEG on a waking 6-year-old male revealed rapid horizontal
      and then vertical eye movements and 10 sec later showed ictal rhythms maximal on
      the occipital areas, quickly spreading to all other areas. A second ictal event
      during wakefulness was very similar to the first. During sleep interictal
      discharges were seen from the right frontal-temporal area and one more ictal
      event was noted. This latter seizure in the NREM sleep record did not show any
      eye movements, but showed ictal activity on the right frontal-temporal area,
      which later became generalized. We propose that the interictal discharges on the
      right frontal-temporal area likely arose from the amygdala, which activated the
      pontine nuclei responsible for PGO (ponto-geniculo-occipital) spikes and the
      rapid eye movements seen in our patient. The PGO spikes activated the occipital
      areas, which then showed clear ictal rhythms to complete the sequence of events.
      This case demonstrates a sequence of rapid eye movements without ictal patterns,
      followed by seizure rhythms, but may still be an example of "epileptic
      nystagmus," assuming that the eye movements arose from an ictal activation of the
      deep subcortical portion of the PGO system.

PMID- 12515452
TI  - Henry Rapoport.

PMID- 12515453
TI  - The preparation and utility of bis(sulfinyl)imidoamidine ligands for the copper
      catalyzed Diels-Alder reaction.
AB  - The design and preparation of a novel class of ligands based on the sulfinyl
      imine functionality is described. In particular, an efficient and modular
      synthesis of bis(sulfinyl)imidoamidine (siam) ligands is reported. The
      versatility of the synthetic sequence is demonstrated by the preparation of
      various analogues to explore the effect of substitution about the ligand
      framework on catalytic activity. The utility of the siam ligands in asymmetric
      catalysis is demonstrated in the Cu(II)-catalyzed Diels-Alder reaction where
      highly enantio- and diastereoselective reactions are reported for a range of N
      acyloxazolidinone dienophile and diene substrate combinations. Of particular note
      is the efficiency of these asymmetric catalysts for reactions involving
      challenging and relatively unreactive acyclic diene substrates. Finally,
      structural data are provided for several ligands as well as metal-ligand
      complexes.

PMID- 12515454
TI  - Borane-mediated aldol cycloreduction of monoenone monoketones: diastereoselective
      formation of quaternary centers.
AB  - Exposure of monoenone monoketones to catecholborane in THF at ambient temperature
      results in tandem 1,4-reduction-aldol cyclization. For aromatic and
      heteroaromatic enones, six-membered cyclic aldol products are formed in excellent
      yield with high levels of syn diastereoselectivity. Five-membered ring formation
      proceeds less readily, but the yield of cyclized product is improved through
      introduction of Rh(I) salts.

PMID- 12515455
TI  - Studies on the enantioselective catalysis of photochemically promoted
      transformations: "sensitizing receptors" as chiral catalysts.
AB  - A strategy for the enantioselective catalysis of photomediated reactions in
      solution is described, involving the use of chiral molecular receptors possessing
      appendant triplet-sensitizing moieties. Energy transfer is selectively directed
      to bound substrate as a consequence of the distance dependence of triplet-triplet
      energy transfer. This effect, which is equivalent to a binding-induced rate
      enhancement, enables substoichiometric chirality transfer from the receptor
      template to the substrate, as observed in the intramolecular enone-olefin photo[2
      + 2]cycloaddition of a quinolone substrate.

PMID- 12515456
TI  - Dynamic helical chirality of an intramolecularly hydrogen-bonded bisoxazoline.
AB  - The synthesis and conformational properties of 2,6-bis-[2-((4S)-4-methyl-4,5
      dihydro-1,3-oxazol-2-yl)phenyl]carbam oylpyridines, 2, have been described.
      Bisoxazoline 2a was prepared in five steps from 2-nitrobenzoyl chloride in an
      overall yield of 71%. In contrast to related structures such as 1, bisoxazoline
      2a exhibits a highly biased P-type helical conformation in solution and in the
      solid state. In the crystal lattice, 2a further assembles into a left-handed
      helical superstructure aligned along the crystallographic c axis. The barrier to
      helical interconversion, as measured by line-shape analysis of the temperature
      dependent (1)H NMR spectra of thiobenzyl derivative 2b, was determined to be
      quite low ((Delta)G(++) = 12.3 kcal/mol), indicating the presence of a highly
      dynamic helical chirality.

PMID- 12515457
TI  - Enantioselective synthesis of alpha-amino acids from N-tosyloxy beta-lactams
      derived from beta-keto esters.
AB  - A novel synthetic sequence has been developed to convert simple beta-keto esters
      into enantiomerically enriched alpha-amino acids. The key features of this
      sequence include the addition of azide to the C3 position of beta-keto ester
      derived N-tosyloxy-beta-lactams through a concomitant nucleophilic addition/N-O
      bond reduction reaction, a mild CsF-induced N1 benzylation of alpha-azido
      monocyclic beta-lactams, the preparation of alpha-keto-beta-lactams through a
      novel four-step sequence from the corresponding 3-azido-1-benzyl-beta-lactams,
      and TEMPO-mediated ring expansion of these compounds to the corresponding N
      carboxy anhydrides (NCAs). In addition, the synthesis, isolation, and
      characterization of unusual 3-imino and 3-chloramino-beta-lactams is reported.

PMID- 12515458
TI  - An enantioselective synthesis of differentially protected erythro-alpha,beta
      diamino acids and its application to the synthesis of an analogue of rhodopeptin
      B5.
AB  - Methodology for the enantioselective synthesis of differentially protected
      erythro-alpha,beta-diamino acids from N-tosyloxy beta-lactams is reported. The
      requisite N-tosyloxy beta-lactams are readily available from simple beta-keto
      esters. The reported approach is flexible and compatible with a variety of
      functional groups. The synthetic utility of the method is demonstrated through
      its application to the preparation of an analogue of the antifungal cyclic
      peptide rhodopeptin B5.

PMID- 12515459
TI  - Novel stereoselective synthesis of functionalized oxazolidinones from chiral
      aziridines.
AB  - Enantiomerically pure N-(R)-alpha-methylbenzyl-4(R)-(chloromethyl)oxazolidinones
      (4R)-5a-k were synthesized in one step and high yields from various aziridine-2
      methanols (S)-2a-k by intramolecular cyclization with phosgene. The alpha
      methylbenzyl substituent on the nitrogen was easily cleaved to give both
      enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a. (R)-7a was used
      for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a-j. We
      also applied the same methodology to prepare oxazolidinones 9a-c containing a
      heteroatom-substituted alkyl group at C-4 in high yields.

PMID- 12515460
TI  - An efficient procedure for the preparation of 4-substituted 5-aminoimidazoles.
AB  - The preparation of O-methylimidates from alpha-aminonitriles and their subsequent
      co-cyclization with primary amines to afford 4-substituted 5-aminoimidazoles was
      studied. It was found that the mildly acidic pyridinium p-toluenesulfonate
      efficiently catalyzed each stage of the reaction sequence: (a) the formation of
      the O-methylimidates, (b) their co-cyclization with a variety of primary amines,
      and (c) certain derivatizations of the resultant heterocycles. The developed
      reaction conditions tolerate a wide variety of alpha-aminonitriles and primary
      amine co-reactants. Thus, it is possible to easily prepare a diverse array of
      substituted heterocyclic compounds in good yield. The requisite alpha
      aminonitriles were synthesized either from amino acids or by phase-transfer
      alkylation of a glycine anion equivalent. The unstable free 5-aminoimidazoles
      were normally protected in situ to provide derivatives (methyl imidates or N,N
      dimethylamidines) that were amenable to characterization.

PMID- 12515461
TI  - Synthesis of covalent probes for the radiolabeling of the cannabinoid receptor.
AB  - The main psychoactive constituent of marijuana, (-)-Delta(9)
      tetrahydrocannabinol, produces most of its physiological effects by interacting
      with the CB1 cannabinoid receptor, a membrane protein belonging to the large
      superfamily of G-protein coupled receptors. The 3-D structure of the receptor
      binding site is of value in the design of novel medications for a variety of
      therapeutic indications. To obtain information on the amino acid residues
      associated with this binding site, we have designed and synthesized a
      cannabinergic CB1 ligand prototype carrying an electrophilic isothiocyanato group
      capable of reacting covalently with amino acid residues bearing thiol or
      unprotonated amino groups. The ligand also incorporates an iodide atom, which can
      serve as a high-activity radiolabel. The key step in our synthesis involves a
      rapid intramolecular Diels-Alder reaction of a transiently formed o-quinone
      methide, which proceeds stereospecifically with the formation of the tricyclic
      cannabinoid template. Introduction of the iodo group is the last step in the
      sequence and is compatible with the use of (125)I-radiolabel.

PMID- 12515462
TI  - A general approach to dehydro-Freidinger lactams: ex-chiral pool synthesis and
      spectroscopic evaluation as potential reverse turn inducers.
AB  - Starting from natural alpha-amino acids, a practical synthesis of the dehydro
      Freidinger lactams 9a-h based on the ring-closing olefin metathesis reaction was
      investigated. The presented examples comprise 6-, 7-, 8-, 9-, and 10-membered
      cyclic dipeptide mimics. Structural variations were demonstrated. We approached
      the metathesis precursors 8a-h employing an N-alkylation/peptide-coupling
      strategy. Subsequent ring closure was promoted by the ruthenium-based catalyst
      10a or 10b. The resulting tetraresidue 11d was shown to undergo intramolecular
      hydrogen bonding based on NMR and FT-IR studies. Thus, the development of dehydro
      Freidinger lactams as potential reverse turn inducers stabilizing an
      intramolecular NH(i+3)...CO(i) hydrogen-bond was demonstrated.

PMID- 12515463
TI  - Thiophenes as traps for benzyne. 3. Diaryl sulfides and the role of dipolar
      intermediates.
AB  - The reactions of seven thiophenes with benzyne generated from diphenyliodonium-2
      carboxylate (DPIC) under a standard set of conditions led among other products to
      the formation of alpha- and beta-naphthyl phenyl sulfides 2a and 2b from
      thiophene (1a) and of 2c and 2d from 2-methylthiophene (1b). Dithienyl sulfides
      4a-f were produced from the halothiophenes 1c-g. The structures of the naphthyl
      sulfides were proven by comparison with authentic samples of 2a-f, thus
      eliminating one of two possible mechanisms of formation. The remaining mechanism
      involves [4+2]-cycloaddition of benzyne to thiophene or to an S-phenylthiophenium
      ylide 10 to give the dipolar 2:1 benzyne/thiophene adduct 8 followed by ring
      opening. Stevens-like rearrangements of 11, formed from 10 by proton transfer,
      may also explain the origin of arylated thiophenes such as 12 and 3 found in some
      reactions of benzynes with thiophene.

PMID- 12515464
TI  - Regio- and stereoselectivity of diethylaluminum azide opening of trisubstituted
      epoxides and conversion of the 3 degrees azidohydrin adducts to isoprenoid
      aziridines.
AB  - The regioisomer ratios (3 degrees,2 degrees /2 degrees,3 degrees ), and in some
      cases the stereochemistry, of vicinal azidohydrins formed in reactions of 11
      trisubstituted terpene epoxides with Et(2)AlN(3) in toluene are reported. The
      more highly substituted azide usually predominated (3 degrees,2 degrees /2
      degrees,3 degrees ratios >or= 40:1 to 2.5-1) in accord with a Markovnikov
      orientation and an S(N)1-like transition state. Reversed regioisomer ratios were
      observed with 6,7-epoxygeranyl acetate (1:2.5) and cis-1,2-epoxylimonene (1:3.3
      to 1:10). The tertiary azido diols from 2,3-epoxygeraniol, 2,3-epoxyfarnesol, and
      2,3-epoxynerol were formed as single isomers with inversion of configuration at
      C3 (>or= 35-40:1 for the C(10) azido diols). The regioselectivity was affected by
      the presence and proximity of oxy functional groups on the epoxide substrate (OH,
      OAc, and OSi-tBuMe(2)), the equivalents of Et(2)AlN(3), and additives (EtOAc or
      EtOH). The results and trends are rationalized by consideration of the structural
      and stereoelectronic characteristics of proposed diethylaluminum epoxonium ion
      intermediates and transition states, together with the nucleophilicity of the
      azide donor. Six of the 3 degrees,2 degrees azidohydrins were converted to the
      corresponding aziridines by primary-selective silylations of four azido diols,
      mesylations, and reductive cyclizations with LiAlH(4).

PMID- 12515465
TI  - Biosynthesis of 4-methylproline in cyanobacteria: cloning of nosE and nosF genes
      and biochemical characterization of the encoded dehydrogenase and reductase
      activities.
AB  - The biosynthesis of the unusual amino acid 4-methylproline in the Nostoc genus of
      cyanobacteria was investigated on the genetic and enzymatic level. Two genes
      involved in the biosynthesis were cloned and the corresponding enzymes, a zinc
      dependent long-chain dehydrogenase and a Delta(1)-pyrroline-5-carboxylic acid
      (P5C) reductase homologue, were overexpressed in Escherichia coli and
      biochemically characterized. Putative substrates were synthesized to test enzyme
      substrate specificities, and deuterium labeling studies were carried out to
      reveal the stereospecificities of the enzymatic reactions with respect to the
      substrates as well as to the coenzymes.

PMID- 12515466
TI  - Efficient syntheses of benzothiazepines as antagonists for the mitochondrial
      sodium-calcium exchanger: potential therapeutics for type II diabetes.
AB  - Type II diabetes mellitus is a chronic metabolic disorder that can lead to
      serious cardiovascular, renal, neurologic, and retinal complications. While
      several drugs are currently prescribed to treat type II diabetes, their efficacy
      is limited by mechanism-related side effects (weight gain, hypoglycemia,
      gastrointestinal distress), inadequate efficacy for use as monotherapy, and the
      development of tolerance to the agents. Consequently, combination therapies are
      frequently employed to effectively regulate blood glucose levels. We have focused
      on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for
      diabetes drug discovery. We have proposed that inhibition of the mNCE can be used
      to regulate calcium flux across the mitochondrial membrane, thereby enhancing
      mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated
      insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report
      the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2
      aminobenzhydrols. The syntheses of other bicyclic analogues based on
      benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates
      are also described. These compounds have been evaluated for their inhibition of
      mNCE activity, and the results from the structure-activity relationship (SAR)
      studies are discussed.

PMID- 12515467
TI  - A novel synthesis of 5-functionalized oxazolidin-2-ones from enantiomerically
      pure 2-substituted N-[(R)-(+)-alpha-methylbenzyl]aziridines.
AB  - 5-Funtionalized enantiomerically pure oxazolidin-2-ones were prepared in one pot
      from commercially available chiral aziridines bearing an electron-withdrawing
      group at C-2 with retention of the configuration in high yields by regioselective
      aziridine ring-opening followed by intramolecular cyclization.

PMID- 12515468
TI  - Enantiospecific synthesis of carbapentostatins.
AB  - In this paper we describe enantioselective syntheses of (+)-carbapentostatin (8)
      and its cyclopentyl analogue 12b. A new and efficient one-pot, two-step
      preparation of aldehyde 15 has been developed, based on the borane reduction of N
      Pf-protected L-aspartic acid gamma-methyl ester (13) and Swern oxidation of the
      resulting alcohol. Homologation to diester 18 and ring formation by Dieckman
      cyclization, followed by reduction and dehydration steps, afford the 4-amino-1
      cyclopentenemethanol derivative 22. Hydroboration and oxidation transform this
      compound stereospecifically into aminocyclopentanol 26, the key aminocyclitol
      component for an asymmetric synthesis of (+)-carbapentostatin.

PMID- 12515469
TI  - Preparation of unsymmetrical sulfonylureas from N,N'-sulfuryldiimidazoles.
AB  - The synthetic methods reported in the literature for the preparation of
      sulfonylureas tend to be restricted in scope or unsuitable for use in parallel
      synthesis. We have developed a method for preparing sterically congested
      sulfonylureas based on N,N'-sulfuryldiimidazole that is both convenient and
      amenable to parallel synthesis. Sequential activation by way of alkylation of the
      imidazole group using methyl triflate followed by nucleophilic displacement with
      a variety of amines and anilines afford the unsymmetrical sulfonylurea.
      Sulfonylureas prepared from anilines were obtained in high yields using N,N'
      sulfuryldiimidazole, while the somewhat more sterically congested analogue, N,N'
      sulfurylbis-2-methylimidazole, proved to be superior for alkylamines.

PMID- 12515470
TI  - Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene with 6,6
      dimethylfulvene: cycloadditions and a rearrangement.
AB  - Reaction of 2,2-bis(trifluoromethyl)-1,1-dicyanoethylene (BTF; 1) with 6,6
      dimethylfulvene (2) affords the expected Diels-Alder cycloadduct, 7-(1
      methylethylidene)-3,3-bis(trifluoromethyl)bicyclo[2.2.1]hept-5-ene-2,2
      dicarbonitrile (3), in good yield. The cycloadduct 3 is unstable and exists in
      equilibrium with the starting materials in less polar solvents. In more polar
      environment, the [4 + 2] adduct 3 either reverts to starting materials, or, in a
      competing process, is converted to the formal [2 + 2] adduct, 2-(1
      methylethylidene)-7,7-bis(trifluoromethyl)bicyclo[3.2.0]hept-3-ene-6,6
      dicarbonitrile (6). In the presence of acid, 3 is converted to a third isomeric
      form, 1,3a,5,6-tetrahydro-7-methyl-5,5-bis(trifluoromethyl)-4H-indene-4,4
      dicarbonitrile (8). Both 6 and 8 are formed with complete regiospecificity.
      Quantum mechanical calculations and X-ray crystallographic studies of this
      ensemble of reactions by BTF, and the analogous set of reactions by its
      progenitor, tetracyanoethylene (TCNE), reveal several interesting facets. The
      conversion of 3 to 6 occurs in certain polar solvents, in the presence of silica
      gel and alumina, as well as in the solid state. Single crystals of 3 were
      observed by X-ray crystallography to undergo crystal-to-crystal rearrangement to
      6. The conversion of 3 to 8 proceeds by the initial retro-Diels-Alder reaction
      followed by isomerization of the fulvene to 1-isopropenyl-1,3-cyclopentadiene
      that then reacts with BTF to give the alternative Diels-Alder product as a single
      regioisomer. A hybrid density functional theory (DFT) method at the B3LYP/6
      31G(d) level of theory gave calculated relative energies of 0.0, -9.0, and -18.8
      kcal/mol for 3, 6, and 8, respectively. The same method was also used to
      correctly predict the regiochemical outcome of the cycloaddition of BTF with 1
      isopropenyl-1,3-cyclopentadiene. Finally, an explanation is offered for the
      preference of the persubstituted cyanoolefins BTF and TCNE to add to the
      exocyclic diene portion of 1-isopropenyl-1,3-cyclopentadiene and the contrasting
      preference of 2-acetyloxy-2-propenenitrile to add to the endocyclic diene.

PMID- 12515471
TI  - Formal enantiospecific synthesis of (+)-FR900482.
AB  - The enantiospecific synthesis of FK973, and thus a formal enantiospecific
      synthesis of the antitumor antibiotic (+)-FR900482, is reported. Addition of
      aniline 8 to chiral epoxide 9, prepared from l-vinylglycine, afforded amino
      alcohol 12. After protection of the aliphatic nitrogen with the 9-phenylfluoren-9
      yl group, to preserve the acidic stereocenter from racemization, formation of the
      aziridine 14 and intramolecular condensation under basic conditions gave
      azocinone 15. Hydroxymethylation at the benzylic position was achieved by a
      process involving methylenation, epoxidation, and hydrogenolysis; the absolute
      stereochemistry of the resulting alcohol 23 was determined by X-ray
      crystallographic analysis. The hydroxyl group of 23 was carbamoylated, and the
      aromatic amine was deprotected electrochemically and then oxidized to give an
      unstable hydroxylamine that was immediately protected as acetate 26. Oxidation of
      26 with DMP, followed by hydrazinolysis of the acetyl group led to spontaneous
      closure of the resulting N-hydroxyamino ketone to hemiketal 28, which can be
      considered as a fully protected precursor of FR900482 and derivatives. Acid
      treatment to remove the protecting groups and acetylation afforded the triacetate
      FK973.

PMID- 12515472
TI  - Stereo- and regioselectivity of Pd(0)/InI-mediated allylic additions to aldehydes
      and ketones. In situ generation of allylindium(III) intermediates from N
      acylnitroso Diels-Alder cycloadducts and 1-amino-4-acetoxycyclopentenes.
AB  - Acylnitroso Diels-Alder cycloadduct (11, 37, and 45)- and cyclopentenyl acetate
      (8 and 9)-derived allylindium(III) species were generated in situ from
      palladium(0) catalysts and indium(I) iodide, and the stereo- and regiochemistry
      of their additions to aldehydes and ketones were investigated. Solvent, catalyst,
      and ionic effects were examined for the reaction of N-acetyl cycloadduct (11) and
      benzyloxyacetaldehyde (10). The solvent mixture of THF/H(2)O with
      Pd(OAc)(2).PPh(3) catalysis was found to be optimal. The addition of N-acetyl
      cycloadduct to aliphatic aldehydes afforded products in good yields and high
      regio- and stereoselectivity, with the cis-1,4-isomers constituting 90-95% of the
      products. The reactions with N-Boc (37a) and N-methylcarbamate (37b) cycloadducts
      also gave the cis-1,4-products predominantly. The same regio- and
      stereoselectivity applied to the reactions of 4-acetoxy-1-(N
      hydroxyphenyacetamido)cyclopentene (8). 4-Acetoxy-1-phenylacetamidocyclopentene
      (9), however, afforded trans-1,4-products exclusively. Mechanistic speculations
      involving chelated transition states are described.

PMID- 12515473
TI  - Enantioselective oxidation of di-tert-butyl disulfide with a vanadium catalyst:
      progress toward mechanism elucidation.
AB  - The mechanism of the oxidation of di-tert-butyl disulfide (1) to the chiral
      thiosulfinate (2) by H(2)O(2) catalyzed by bis(acetylacetonato)oxovanadium and a
      chiral Schiff-base ligand (3) has been investigated. Techniques included (51)V
      NMR spectroscopy, solvent effects on reaction enantioselectivity, and the
      isolation and full characterization of a 2:1 ligand-to-vanadium catalyst
      precursor. A model for the dramatic solvent effect on the enantioselectivity of
      this reaction was developed, based on the identification of a competing
      nonselective oxidation pathway. From this model, strategies for limiting this
      competing pathway were developed.

PMID- 12515474
TI  - P-chiral, monodentate ferrocenyl phosphines, novel ligands for asymmetric
      catalysis.
AB  - Eight P-chiral monodentate ferrocenyl phosphines (1a-h) were prepared in high
      enantiomeric excess (>95% ee in most cases) by way of an ephedrine-based
      oxazaphospholidine borane complex. Primary alkyl, secondary alkyl, and
      substituted aromatic substituents were successfully introduced at the phosphorus
      center, along with ferrocenyl and phenyl groups, generating phosphines of the
      general structure FcP(Ph)(R) (Fc = ferrocenyl, R = aryl, alkyl). The synthetic
      route employed provides facile access to a previously undeveloped class of chiral
      monophosphines. These compounds were evaluated as ligands in asymmetric catalytic
      reductive coupling of alkynes and aldehydes and were found to provide the desired
      chiral allylic alcohols with good regioselectivity and ee in many cases and with
      complete (E)-selectivity (>98:2) in all cases.

PMID- 12515475
TI  - Convenient synthesis of 5,6,11,12,17,18- hexahydrocyclononal[1,2-b:4,5-b':7,8
      b'']triindole, a novel phytoestrogen.
AB  - An efficient one-pot synthesis is described of 5,6,11,12,17,18
      hexahydrocyclononal[1,2-b:4,5-b':7,8-b'']triindole (CTr), a potent estrogen
      agonist from food plants. For the procedure, gramine is treated with dimethyl
      sulfate and sodium in ethanol at room temperature. Quenching of the reaction with
      water and workup of the product provides CTr in approximately 75% yield.

PMID- 12515476
TI  - Synthesis of a bisubstrate analogue targeting estrogen sulfotransferase.
AB  - Sulfotransferases catalyze the transfer of a sulfuryl group from the eukaryotic
      sulfate donor 3'-phosphoadenosine 5'-phosphosulfate to an acceptor biomolecule.
      Sulfotransferases have been linked with several disease states, prompting our
      investigation of specific sulfotransferase inhibitors. Presented herein is the
      synthesis and evaluation of a bisubstrate analogue designed to inhibit estrogen
      sulfotransferase. The synthesis utilizes a novel, orthogonally protected 3'
      phosphoadenosine 5'-phosphate (PAP) derivative allowing the selective
      functionalization of the 5'-phosphate with a sulfate acceptor mimic. Kinetic
      studies revealed significant inhibitory activity and provide guidance for
      improved inhibitor design.

PMID- 12515477
TI  - Unnatural amino acid mutagenesis of green fluorescent protein.
AB  - Unnatural amino acid mutagenesis has been used to selectively substitute tyrosine
      66 of green fluorescent protein (GFP) with five novel amino acids: p-amino-L
      phenylalanine, p-methoxy-L-phenylalanine, p-iodo-L-phenylalanine, p-bromo-L
      phenylalanine, and L-3-(2-naphthyl)alanine. The absorbance and emission maxima of
      the resulting mutant GFPs span the range from 375 to 435 nm and 428 to 498 nm,
      respectively. The spectral properties of the mutant GFPs, including the
      absorbance and fluorescence maxima and quantum yields, correlate with the
      structural and electronic properties of the substituents on the amino acids.

PMID- 12515478
TI  - Serine as chiral educt for the practical synthesis of enantiopure N-protected
      beta-hydroxyvaline.
AB  - N-tert-Butyloxycarbonyl- and N-benzenesulfonyl-beta-hydroxyvalines 1a and 1b
      were, respectively, synthesized in enantiomerically pure form by a two-step
      protocol from their enantiomeric N-protected serine methyl esters 2a and 2b. The
      addition of CH(3)MgBr to 2a and 2b provided diols 3a and 3b, respectively as
      major products in 83% and 81% yields. Selective oxidation of diols 3a and 3b was
      performed using a TEMPO, NaClO(2), NaOCl cocktail in 96% and 93% respective
      yields. This two-step process effectively furnished multigram amounts of
      enantiopure N-Boc-beta-hydroxyvaline 1a.

PMID- 12515479
TI  - Indium-mediated reductive elimination of halohydrins.
AB  - Olefin formation has been successfully carried out by reductive elimination
      reactions of halohydrins with Pd(PPh(3))(4)/In/InCl(3) in aqueous media.

PMID- 12515480
TI  - The combined solid/solution-phase synthesis of nitrosamines: the evolution of the
      "libraries from libraries" concept.
AB  - The generation of diverse chemical libraries using the "libraries from libraries"
      concept by combining solid-phase and solution-phase methods is described. The
      central features of the approaches presented are the use of solid-phase synthesis
      methods for the generation of a combinatorial polyamine library. Following
      cleavage from the resin with HF, the polyamine library was reacted with ethyl
      nitrite in the solution phase to yield the desired nitrosamine library in good
      yield and purity. The approaches described enable the efficient syntheses of
      individual nitrosamines as well as mixture-based nitrosamine libraries.

PMID- 12515481
TI  - Asymmetric synthesis of the carbapenam core from serine.
AB  - The stereospecific synthesis of the functionalized carbapenam core 16 from the
      serine-derived trisubstituted pyrrolidine 9 is reported. The synthetic strategy
      relies on synthesizing an appropriately functionalized pyrrolidine, followed by
      an intramolecular azetidone formation utilizing a modified Mukiyama reagent. The
      efficient one-pot conversion of the benzenesulfonamide-protected pyrrolidine 9 to
      the Cbz-protected pyrrolidine 10 is also reported.

PMID- 12515482
TI  - The preparation of a fully differentiated "multiwarhead" siderophore precursor.
AB  - A protected, fully differentiated siderophore analogue has been prepared so that
      "Trojan Horse"-like siderophore drug conjugates with different drugs can be
      synthesized. The key steps in the synthesis include controlled preparation of an
      unsymmetrical urea and its conversion to a fully differentiated isocyanurate by
      reaction with chloro(carbonyl) isocyanate.

PMID- 12515483
TI  - Synthesis of N-Fmoc-O- (N'-Boc-N'-methyl)-aminohomoserine, an amino acid for the
      facile preparation of neoglycopeptides.
AB  - The synthesis of N-Fmoc-O-(N'-Boc-N'-methyl)-aminohomoserine in 35% overall yield
      from l-homoserine is described. This amino acid can be efficiently incorporated
      into peptides using Fmoc-chemistry-based solid-phase peptide synthesis, and the
      resulting peptides can be chemoselectively glycosylated at the aminooxy side
      chains to generate neoglycopeptides. The synthesis of this derivative greatly
      expands the availability of a previously developed neoglycopeptide synthesis
      strategy.

PMID- 12515484
TI  - Recent Reviews. 67.
AB  - Reviews are listed in order of appearance in the sources indicated. In
      multidisciplinary review journals, only those reviews which fall within the scope
      of this Journal are included. Sources are listed alphabetically in three
      categories: regularly issued review journals and series volumes, contributed
      volumes, and other monographs. Titles are numbered serially, and these numbers
      are used for reference in the index. Major English-language sources of critical
      reviews are covered. Encyclopedic treatises, annual surveys such as Specialist
      Periodical Reports, and compilations of symposia proceedings are omitted. This
      installment of Recent Reviews covers principally the middle part of the 2002
      literature. Previous installment: J. Org. Chem. 2002, 67(20), 7169-74. SUPPORTING
      INFORMATION AVAILABLE: A file containing this Recent Review compilation in
      Microsoft Word and the data in rtf format. This material is available free of
      charge via the Internet at http://pubs.acs.org.

PMID- 12515485
TI  - 124 years of publishing original and primary chemical research: 135,149
      publications, 573,453 pages, and a century of excellence.

PMID- 12515486
TI  - Dinitrogen reduction by TmII, DyII, and NdII with simple amide and aryloxide
      ligands.
AB  - Dinitrogen can be reduced to the planar M2(mu-eta2:eta2-N2) structure without
      employing cyclopentadienyl or complicated polydentate ligands using the recently
      discovered divalent oxidation states of Tm(II), Dy(II), and Nd(II). Complexes of
      these ions with common monodentate amide and aryloxide ligands can effect N2
      reduction. THF solutions of LnI2 (Ln = Tm, Dy) in the presence of 2 equiv of
      NaN(SiMe3)2 reduce dinitrogen to form {[(Me3Si)2N]2(THF)Ln}2(mu-eta2:eta2-N2)
      complexes that have planar Ln2N2 units and 1.264(7) and 1.305(6) A NN bonds
      consistent with (N2)2- moieties. With the stronger reductant Nd(II), aryloxides
      are sufficient ancillary ligands: the NdI2/2KOC6H3tBu2-2,6 (KOAr) system forms
      [(ArO)2(THF)2Nd]2(mu-eta2:eta2-N2), which has a 1.242(7) A NN bond.

PMID- 12515487
TI  - "Inverse-electron-demand" ligand substitution in palladium(0)-olefin complexes.
AB  - Ligand substitution reactions are ubiquitous in transition-metal chemistry and
      catalysis. Investigation of ligand substitution reactions for a series of
      electron-rich palladium(0)-olefin complexes, (bathocuproine)Pd(nitrostyrene)
      reveals an unprecedented mechanism in which the metal serves as the nucleophilic
      partner in an "associative" substitution pathway.

PMID- 12515488
TI  - Virus-ligand interactions: identification and characterization of ligand binding
      by NMR spectroscopy.
AB  - We demonstrate the detection and characterization of ligand binding to viruses
      via NMR. To illustrate the methodology, the interaction of an antiviral compound
      with human rhinovirus serotype 2 (HRV2) was investigated. Specific interaction of
      a capsid-binding inhibitor and native HRV2 was monitored utilizing saturation
      transfer difference (STD) NMR. STD NMR experiments at atomic resolution allowed
      those regions of the ligand that are involved in the interaction with the virus
      to be determined. The approach allows for (i) the fast and robust assessment of
      binding, (ii) the determination of the ligand binding epitope at atomic
      resolution without the necessity to crystallize virus-ligand complexes, and (iii)
      the reuse of the virus in subsequent assays. This methodology enables one to
      easily identify binding of drugs, peptides, and receptor or antibody fragments to
      the viral capsid.

PMID- 12515489
TI  - Kinetic and stereochemical evidence for the involvement of only one proline
      molecule in the transition states of proline-catalyzed intra- and intermolecular
      aldol reactions.
AB  - Contrary to the widely accepted mechanism of the Hajos-Parrish-Eder-Sauer
      Wiechert reaction, we have obtained evidence for the involvement of only one
      proline molecule in the transition states of both inter- and intramolecular aldol
      reactions. Our conclusions are based on kinetic measurements and the absence of
      nonlinear and dilution effects on the asymmetric catalysis, and are supported by
      B3LYP/6-31G* calculations. Complementary to recent theoretical studies, our
      results provide the foundation of a unified enamine catalysis mechanism of
      proline-catalyzed inter- and intramolecular aldol reactions.

PMID- 12515490
TI  - 13C NMR spectroscopy of 13C1-labeled octanethiol-protected Au nanoparticles:
      shifts, relaxations, and particle-size effect.
AB  - We report here an investigation of metal-ligand interactions in nanoparticles
      with 13C NMR, using a labeled 13C1-octanethiol, a protecting ligand for self
      assembled monolayer (SAM) systems, in which close proximity of the 13C1 to the
      metal surface serves as an effective probe for the changing electronic
      environment. Several remarkable results have been obtained: as the metal core
      size increases from 1.6 to 4.0 nm, the 13C1 spectrum is downshifted from 40.5 to
      53 ppm, and the spin-spin relaxation rate, T2-1, increases while the spin-lattice
      relaxation ratio decreases. Although the spin-lattice relaxation may be due to
      particle tumbling and ligand motion in the liquid state, the main source of the
      spin-spin relaxation, and NMR shift, is most possibly due to the changing
      electronic properties of the metal core.

PMID- 12515491
TI  - Designing the selectivity of the fluorescent detection of amino acids: a
      chemosensing ensemble for histidine.
AB  - The imidazole group of histidine deprotonates and bridges the two CuII centers of
      a dimetallic polyamine macrocyclic complex, displacing the previously bound and
      quenched fluorescent indicator I. Thus, histidine recognition is signaled by the
      revival of the fluorescence of I. Selectivity with respect to other natural amino
      acids is achieved by choosing an indicator of tuned affinity toward the
      dicopper(II) receptor.

PMID- 12515492
TI  - A novel calcium-dependent bacterial phosphatidylinositol-specific phospholipase C
      displaying unprecedented magnitudes of thio effect, inverse thio effect, and
      stereoselectivity.
AB  - Understanding the potential range of enzymatic thio effects (kO/kS) is of great
      value when using sulfur-substituted phosphate analogues to study phosphoryl
      transfer reactions in enzymes and ribozymes. Herein we report that a newly
      discovered Ca2+-dependent Streptomyces antibioticus phosphatidylinositol-specific
      phospholipase C and its mutants display unprecedented magnitudes of thio effect,
      inverse thio effect, and RP/SP stereoselectivity. We demonstrate that for a
      single enzyme the bridging thio effect can vary from 0.002 to 20 and the
      nonbridging thio effect can vary from 1 to 108. These values fall outside the
      range of those reported for nonenzymatic reactions, emphasizing the need for
      cautious interpretation when using thio effects to elucidate details of enzyme
      catalysis.

PMID- 12515493
TI  - The crystallographic structure of a Lewis acid-assisted chiral Bronsted acid as
      an enantioselective protonation reagent for silyl enol ethers.
AB  - It is difficult to control the enantioselectivity in the protonation of silyl
      enol ethers with simple chiral Bronsted acids, mainly due to bond flexibility
      between the proton and its chiral counterion, the orientational flexibility of
      the proton, and the fact that the proton sources available are limited to acidic
      compounds such as chiral carboxylic acids. To overcome these difficulties, we
      have developed a Lewis acid-assisted chiral Bronsted acid (LBA) system. The
      coordination of Lewis acids with Bronsted acids restricts the orientation of
      protons and increases their acidity. Optically active binaphthol (BINOL)
      derivative.SnCl4 complexes are very effective as enantioselective protonation
      reagents for silyl enol ethers. However, their exact structures have not yet been
      determined. We describe here optically active 1,2-diarylethane-1,2-diol
      derivative.SnCl4 as a new type of LBA for the enantioselective protonation as
      well as its crystallographic structure. A variety of optically active 1,2
      diarylethane-1,2-diols could be readily prepared by asymmetric syn
      dihydroxylation. This is a great advantage over BINOL for the flexible design of
      a new LBA. The most significant finding is that we were able to specify the
      conformational direction of the H-O bond of LBA, which has some asymmetric
      inductivity, by X-ray diffraction analysis. The stereochemical course in the
      enantioselective protonation of silyl enol ethers using LBA would be controlled
      by a linear OH/pi interaction with an initial step. The absolute stereopreference
      in enantioselective reactions using BINOL.SnCl4 can also be explained in terms of
      this uniformly mechanistic interpretation.

PMID- 12515494
TI  - Conformation-activity relationships in polyketide natural products: a new
      perspective on the rational design of epothilone analogues.
AB  - The syntheses of C14-methyl analogues of epothilone B and D are described.
      Conformational analysis using computational methods, X-ray crystallography, and
      NMR studies showed that the stereochemistry at C14 has a pronounced effect on the
      conformation of the epoxide region. Biological assays indicated significant
      differences in their biological activity. Substitution which stabilized conformer
      I retained significant biological activity. In contrast, substitution which
      stabilized conformer II provided analogues with no measurable cytotoxicity. The
      conformation-activity relationships strongly support the importance of conformer
      I as the bioactive conformation of the epoxide region of epothilone. The approach
      presented here offers a new perspective on rational design of modified
      biologically active polyketides.

PMID- 12515495
TI  - Remarkably large positive and negative allosteric effects on ion recognition by
      the formation of a novel helical pseudocryptand.
AB  - In supramolecular chemistry, a great deal of attention has focused on regulating
      guest binding via an external stimulus. To utilize the same effector for both
      highly guest-selective positive and negative allosteric effects, however,
      stricter and more precise regulation of the host structure is required. A novel
      allosteric host 1 binds Fe(II) to afford the pseudocryptand, 1.Fe(II), which
      bears a cavity that is surrounded by three polyether chains in a helical fashion.
      The binding selectivity of 1 (Na+ > K+ > Rb+ > Cs+) is the opposite of 1.Fe(II)
      (Cs+ > Rb+ > K+ > Na+). Single-ion transport through a liquid membrane shows ion
      selectivity similar to the equilibrium constants. To the best of our knowledge,
      this is the first example of an allosteric recognition system, in which the same
      effector, that is, Fe(II), exhibits both large positive and negative allosteric
      effects on equilibrium and dynamic recognition events. The X-ray analysis and 1H
      NMR examination indicate that the combination of the macrobicyclic effect and the
      intramolecular interchain interactions (CH-pi interaction and steric hindrance)
      finely controls the positive and negative allosteric effects, which depend on the
      size of the guest. The helical framework opens a new general method for
      constructing more sophisticated, controllable receptors for helical biomolecules,
      for example, DNA and proteins, and helical molecular devices such as a molecular
      coil or spring responding to a stimulus.

PMID- 12515496
TI  - Intramolecular endo-dig hydrosilylation catalyzed by ruthenium: evidence for a
      new mechanistic pathway.
AB  - The ruthenium catalyst [Cp*Ru(MeCN)3]PF6 effects a novel intramolecular
      hydrosilylation of homo- and bis-homopropargylic alcohols, producing products of
      unique regioselectivity under very mild conditions with excellent selectivity.
      The reaction is compatible with a wide range of functional groups and tolerates
      substantial steric bulk. In addition to producing valuable synthetic
      intermediates thus far obtainable only in circuitous fashion, the results imply
      the necessity for a reexamination of the mechanism surrounding trans
      hydrosilylation reactions, at least for ruthenium catalysts. At the very least, a
      simple cis addition/isomerization mechanism almost certainly cannot be active in
      this case. A silicon-ruthenium transposition could potentially provide a
      rationalization. However, the evidence for any products of syn addition with
      nonhydrido ruthenium catalysts is very scarce. Alternatively, a direct trans
      addition to orthogonal p-systems is also a possibility.

PMID- 12515497
TI  - A dihydroxo-bridged Fe(II)-Fe(III) complex: a new member of the diiron diamond
      core family.
AB  - The first structurally characterized Fe(II)-Fe(III) complex containing a M2(mu
      OH)2 diamond core is a Robin and Day class II mixed-valence complex.

PMID- 12515498
TI  - Dipole-induced polymorphs of trans-2-hydroxycycloheptanecarboxylic acid with
      virtually the same unit cell.
AB  - The polymorphs of trans-2-hydroxycycloheptanecarboxylic acid have exactly the
      same lattice parameters and thus mimic isomorphism. They differ only in their
      space group: Pna21 versus Pn21a. In form II, the screw axes turn the 18-membered
      rings of hydrogen-bonded tetramers around the b axis. In this way, the stacking
      of the layers becomes antiparallel, which cancels out the dipoles within the unit
      cell. In form I, the same turn around the c axis leaves the stacking of the
      layers parallel. Thus, the dipoles are canceled out by antiparallel domains in
      the crystals. Between the antiparallel domains of I, each frontier is a double
      layer of II. This implies that (a) a pure form of I cannot be isolated and (b)
      the percentage of II in I may alter from crystal to crystal.

PMID- 12515499
TI  - Anodic cyclization reactions: the total synthesis of alliacol a.
AB  - An anodic cyclization-Friedel Crafts alkylation strategy has been used to rapidly
      assemble the core ring system of alliacol A and to complete a formal total
      synthesis of the natural product. The anodic cyclization reaction was used to
      effect the coupling of a nucleophilic furan ring to the normally nucleophilic
      carbon of a silyl enol ether. The substrate for this initial cyclization reaction
      contained all of the carbons needed for completing the total synthesis. The
      electrolysis proceeded in high yield and could be accomplished with the use of a
      6 V lantern battery.

PMID- 12515500
TI  - Very high-field EPR study of glycyl radical enzymes.
AB  - This work shows that very high-field EPR spectroscopy allows a rather accurate
      determination of the g-tensor of protein radicals, including C-centered ones, and
      thus may be used as a probe for distinguishing a tyrosyl-, a glycyl-, or a
      tryptophanyl-radical. In this paper, we report the first complete analysis of the
      g-tensor of glycyl radical enzymes (anaerobic ribonucleotide reductase, pyruvate
      formate lyase, and benzylsuccinate synthase), thus providing new information on
      their EPR properties. Because the g-anisotropy is small, the complete resolution
      of the g-tensor could be only obtained at very high field (18.8 T).

PMID- 12515501
TI  - An unusual equilibrium chlorine atom transfer process and its potential for
      assessment of steric pressure by bulky aryls.
AB  - An unusually facile intermolecular chlorine atom transfer process has been
      discovered between the phospha-Wittig reagents ArP=PMe3 and ArPCl2 (Ar is a
      sterically hindered aryl group). The atom transfer process is catalyzed by added
      PMe3. A mechanism is forwarded that is based upon a Me3P/Me3PCl2 couple that
      allows shuttling of chlorine atoms between ArP groups. This unique transfer
      process is exploited to evaluate the steric properties of aryl groups via an
      equilibrium process.

PMID- 12515502
TI  - G-quadruplex formation of thrombin-binding aptamer detected by electrospray
      ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry detected the formation of the G
      quadruplex structure of the thrombin-binding aptamer, d(GGTTGGTGTGGTTGG), and
      established its specific interaction with metal ions. One piece of evidence that
      the bonding in the gas phase is via the G-quadruplex form is the enhanced
      binding, with respect to other metal ions, of the aptamer with Sr2+, Pb2+, Ba2+,
      and K+, which are of similar size. Another is the lack of specific binding with
      controls in which the G's are replaced with A's. The most convincing evidence is
      the extent of H/D exchange of the gas-phase aptamer as compared to that bound to
      K+ and Sr2+. The latter two complexes exchange six and nine fewer H's, indicating
      a significant increase in protection upon binding to the metals. Mass
      spectrometry will be an important tool in understanding G-quadruplexes, which are
      particularly important in DNA telomers.

PMID- 12515503
TI  - High-accuracy residual 1HN-13C and 1HN-1HN dipolar couplings in perdeuterated
      proteins.
AB  - Truncation by the presence of many short-range residual dipolar couplings (RDCs)
      hinders the observation of long-range RDCs in weakly aligned biomacromolecules.
      Perdeuteration of proteins followed by reprotonation of labile hydrogen positions
      greatly alleviates this problem. Here we show that for small perdeuterated
      proteins, a large number (up to 10 in protein G) of long-range RDCs to 13C and
      1HN can be observed from individual amide protons. The 1HN <--> 13C RDCs comprise
      correlations to 13Calpha, 13Cbeta, and 13C' nuclei of the same and the preceding
      amino acid, as well as 13C' nuclei of hydrogen-bonded amino acids. The accuracy
      of the coupling constants is very high and defines individual internuclear
      distances to within few picometers. Deviations between measured RDC values and
      values predicted from the 1.1 A crystal structure of protein G are mainly found
      in two surface-exposed loop regions. The deviations show a strong correlation to
      the B-factor of the crystal structure.

PMID- 12515504
TI  - Total synthesis of gambierol.
AB  - The convergent total synthesis of gambierol (1) is described. The octacyclic
      ether framework of 1 was constructed via the intramolecular allylation of alpha
      chloroacetoxy ether followed by ring-closing metathesis. A modified Stille
      coupling was successfully applied to the synthesis of the triene side chain.

PMID- 12515505
TI  - A DFT-derived model predicts solvation-dependent configurational stability of
      organolithium compounds: a case study of a chiral alpha-thioallyllithium
      compound.
AB  - Density functional theory calculations (B3LYP/6-31+G*) were performed to evaluate
      a model previously published by us which suggests that aggregation and solvation
      of organolithium compounds can be of large importance for their configurational
      stability. In this study, we demonstrate how THF solvation of the monomer of a
      chiral alpha-thioallyllithium compound impedes the racemization, while upon
      dimerization the inversion process accelerates. These findings agree with
      experiments performed by Hoppe and co-workers. These findings may be used to
      further develop organolithium compounds which should be designed to resist
      aggregation and efficient transition-state solvation.

PMID- 12515506
TI  - DNA interchain cross-links formed by acrolein and crotonaldehyde.
AB  - Acrolein and higher alpha,beta-unsaturated aldehydes are bifunctional genotoxins.
      The deoxyguanosine adduct of acrolein, 3-(2-deoxy-beta-d-erythro-pentofuranosyl)
      5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N(2)
      propanodeoxyguanosine, 2a), is a major DNA adduct formed by acrolein. The
      potential for oligodeoxynucleotide duplexes containing 2a to form interchain
      cross-links was evaluated by HPLC, CZE, MALDI-TOF, and melting phenomena.
      Interchain cross-links represent one of the most serious types of damage in DNA
      since they are absolute blocks to replication. In oligodeoxynucleotides
      containing the sequence 5'-dC-2a, cross-linking occurred in a slow, reversible
      manner to the extent of approximately 50%. Enzymatic digestion to form 3-(2-deoxy
      beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-(N(2)-2'
      deoxyguanosinyl)pyrimido[1,2-a]purin-10(3H)one (5a) and reduction with NaCNBH(3)
      followed by enzymatic digestion to give 1,3-bis(2'-deoxyguanosin-N(2)-yl)propane
      (6a) established that cross-linking had occurred with the exocyclic amino group
      of deoxyguanosine. It is concluded that the cross-link is a mixture of imine and
      carbinolamine structures. With oligodeoxynucleotide duplexes containing the
      sequence 5'-2a-dC, cross-links were not detected by the techniques enumerated
      above. In addition, (15)N-(1)H HSQC and HSQC-filtered NOESY spectra carried out
      with a duplex having (15)N-labeling of the target amino group established
      unambiguously that a carbinolamine cross-link was not formed. The potential for
      interchain cross-link formation by the analogous crotonaldehyde adduct (2b) was
      evaluated in a 5'-dC-2b sequence. Cross-link formation was strongly dependent on
      the configuration of the methyl group at C6 of 2b. The 6R diastereomer of 2b
      formed a cross-link to the extent of 38%, whereas the 6S diastereomer cross
      linked only 5%.

PMID- 12515507
TI  - NMR determination of the conformation of a trimethylene interstrand cross-link in
      an oligodeoxynucleotide duplex containing a 5'-d(GpC) motif.
AB  - Malondialdehyde interstrand cross-links in DNA show strong preference for 5'
      d(CpG) sequences. The cross-links are unstable and a trimethylene cross-link has
      been used as a surrogate for structural studies. A previous structural study of
      the 5'-d(CpG) cross-link in the sequence 5'-d(AGGCGCCT), where G is the modified
      nucleotide, by NMR spectroscopy and molecular dynamics using a simulated
      annealing protocol showed the guanine residues and the tether lay approximately
      in a plane such that the trimethylene tether and probably the malondialdehyde
      tether, as well, could be accommodated without major disruptions of duplex
      structure [Dooley et al. J. Am Chem. Soc. 2001, 123, 1730-1739]. The trimethylene
      cross-link has now been studied in a GpC motif using the reverse sequence. The
      structure lacks the planarity seen with the 5'-d(CpG) sequence and is skewed
      about the trimethylene cross-link. Melting studies indicate that the trimethylene
      cross-link is thermodynamically less stable in the GpC motif than in the 5
      d(CpG). Furthermore, lack of planarity of the GpC cross-link precludes making an
      isosteric replacement of the trimethylene tether by malondialdehyde. A similar
      argument can be used to explain the 5'-d(CpG) preference for interchain cross
      linking by acrolein.

PMID- 12515508
TI  - Tandem ligation of multipartite peptides with cell-permeable activity.
AB  - To prepare multipartite peptides with several functional cargoes including a cell
      permeable sequence or transportant for intracellular delivery, tandem ligation of
      peptides is a convenient convergent approach with the fewest synthetic steps. It
      links three or four unprotected segments forming two or more regiospecific bonds
      consecutively without a deprotection step. This paper describes a tandem ligation
      strategy to prepare multipartite peptides with normal and branched architectures
      carrying a novel transportant peptide that is rich in arginine and proline to
      permit their cargoes to be translocated across membranes to affect their
      biological functions in cytoplasm. Our strategy consists of three ligation
      methods specific for amino terminal cysteine (Cys), serine/threonine (Ser/Thr),
      and N(alpha)-chloroacetylated amine to afford Xaa-Cys, Xaa-OPro (oxaproline) and
      Xaa-psiGly (pseudoglycine) at the ligation sites, respectively. Assembly of
      single-chain peptides from three different segments was achieved by the tandem
      Cys/OPro ligation to form two amide bonds, an Xaa-Cys and then an Xaa-OPro.
      Assembly of two- and three-chain peptides with branched architectures from four
      different segments was accomplished by tandem Cys/psiGly/OPro ligation. These NT
      specific tandem ligation strategies were successful in generating cell-permeable
      multipartite peptides with one-, two-, and three-chain architectures, ranging in
      size from 52 to 75 residues and without the need of a protection or deprotection
      step. In addition, our results show that there is considerable flexibility in
      architectural design to obtain cell-permeable multipartite peptides containing a
      transportant sequence.

PMID- 12515509
TI  - Single crystal EPR studies of the reduced active site of [NiFe] hydrogenase from
      Desulfovibrio vulgaris Miyazaki F.
AB  - In the catalytic cycle of [NiFe] hydrogenase the paramagnetic Ni-C intermediate
      is of key importance, since it is believed to carry the substrate hydrogen,
      albeit in a yet unknown geometry. Upon illumination at low temperatures, Ni-C is
      converted to the so-called Ni-L state with markedly different spectroscopic
      parameters. It is suspected that Ni-L has lost the "substrate hydrogen". In this
      work, both paramagnetic states have been generated in single crystals obtained
      from the [NiFe] hydrogenase from Desulfovibrio vulgaris Miyazaki F. Evaluation of
      the orientation dependent spectra yielded the magnitudes of the g tensors and
      their orientations in the crystal axes system for both Ni-C and Ni-L. The g
      tensors could further be related to the atomic structure by comparison with the X
      ray crystallographic structure of the reduced enzyme. Although the g tensor
      magnitudes of Ni-C and Ni-L are quite different, the orientations of the
      resulting g tensors are very similar but differ from those obtained earlier for
      Ni-A and Ni-B (Trofanchuk et al. J. Biol. Inorg. Chem. 2000, 5, 36-44). The g
      tensors were also calculated by density functional theory (DFT) methods using
      various structural models of the active site. The calculated g tensor of Ni-C is,
      concerning magnitudes and orientation, in good agreement with the experimental
      one for a formal Ni(III) oxidation state with a hydride (H(-)) bridge between the
      Ni and the Fe atom. Satisfying agreement is obtained for the Ni-L state when a
      formal Ni(I) oxidation state is assumed for this species with a proton (H(+))
      removed from the bridge between the nickel and the iron atom.

PMID- 12515510
TI  - Monolayer assemblies of a de novo designed 4-alpha-helix bundle carboprotein and
      its sulfur anchor fragment on Au(111) surfaces addressed by voltammetry and in
      situ scanning tunneling microscopy.
AB  - Mapping and control of proteins and oligonucleotides on metallic and nonmetallic
      surfaces are important in many respects. Electrochemical techniques based on
      single-crystal electrodes and scanning probe microscopies directly in aqueous
      solution (in situ SPM) have recently opened perspectives for such mapping at a
      resolution that approaches the single-molecule level. De novo design of model
      proteins has evolved in parallel and holds promise for testing and controlling
      protein folding and for new tailored protein structural motifs. In this report we
      combine these two strategies. We present a scheme for the synthesis of a new 4
      alpha-helix bundle carboprotein built on a galactopyranoside derivative with a
      thiol anchor aglycon suitable for surface immobilization on gold. The
      carboprotein with thiol anchor in monomeric and dimeric (disulfide) form, the
      thiol anchor alone, and a sulfur-free 4-alpha-helix bundle carboprotein without
      thiol anchor have been prepared and investigated for comparison. Cyclic and
      differential pulse voltammetry (DPV) of the proteins show desorption peaks around
      -750 mV (SCE), whereas the thiol anchor desorption peak is at -685 mV. The peaks
      are by far the highest for thiol monomeric 4-alpha-helix bundle carboprotein and
      the thiol anchor. This pattern is supported by capacitance data. The DPV and
      capacitance data for the thiolated 4-alpha-helix bundle carboproteins and the
      thiol anchor hold a strong Faradaic reductive desorption component as supported
      by X-ray photoelectron spectroscopy. The desorption peak of the sulfur-free 4
      alpha-helix bundle carboprotein, however, also points to a capacitive component.
      In situ scanning tunneling microscopy (in situ STM) of the thiol anchor discloses
      an adlayer with small domains and single molecules ordered in pin-striped
      supramolecular structures. In situ STM of thiolated 4-alpha-helix bundle
      carboprotein monomer shows a dense monolayer in a broad potential range on the
      positive side of the desorption potential. The coverage decreases close to this
      potential and single-molecule structures become apparent. The in situ STM
      contrast is also strengthened, indicative of a new redox-based tunneling
      mechanism. The data overall suggest that single-molecule mapping of natural and
      synthetic proteins on well-characterized surfaces by electrochemistry and in situ
      STM is within reach.

PMID- 12515511
TI  - Activation barriers in the homolytic cleavage of radicals and ion radicals.
AB  - As revealed by several experimental examples, radicals and ion radicals may, in
      contrast with closed-shell molecules, undergo exothermic homolytic cleavages
      (.A..B --> A: +.B) with substantial activation barriers. A two-state
      semiclassical model is proposed for explaining the existence of the barrier and
      estimating its magnitude. It is based on the intersection of the potential energy
      surfaces characterizing the dissociation of a bonding state, .A..B -->.A. +.B, on
      one hand, and the approach to bonding distance of a repulsive state, A: +.B --> A
      therefore B, on the other. After inclusion of the bond cleavage and formation as
      Morse curves in the normal-mode analysis, a simple activation driving force
      relationship is obtained, the two main ingredients of the intrinsic barrier being
      the triplet excitation energy of the A moiety and the pi*--> sigma* excitation
      energy in .A-B. The model is then tested by quantum chemical calculations, first
      on a simplified system to evaluate the calculation techniques and then on a real
      system. A comparison of the model predictions with experiment is finally
      performed using the rate data recently gathered for the cleavage of 4-cyanophenyl
      alkyl ether anion radicals, which cover a respectable range of driving forces,
      showing satisfactory agreement between theoretical predictions and experimental
      data.

PMID- 12515512
TI  - Optically active iridium imidazol-2-ylidene-oxazoline complexes: preparation and
      use in asymmetric hydrogenation of arylalkenes.
AB  - This work explores the potential of iridium complexes of the N-heterocyclic
      carbene oxazoline ligands 1 in asymmetric hydrogenations of arylalkenes. The
      accessible carbene precursors, imidazolium salts 2, and robust iridium complexes
      5 facilitated a discovery/optimization approach that featured preparation of a
      small library of iridium complexes, parallel hydrogenation reactions, and
      automated analysis. Three of the complexes (5ab, 5ad, and 5dp) and a similar
      rhodium complex (6ap) were studied by single-crystal X-ray diffraction
      techniques. This revealed molecular features of 6ap, and presumably the
      corresponding iridium complex 5ap, that the others do not have. In
      enantioselective hydrogenations of arylalkenes complex 5ap was the best for many,
      but not all, substrates. The enantioselectivities and conversions observed were
      sensitive to minor changes to the catalyst and substrate structure. Ligands with
      aliphatic N-heterocyclic carbene substituents gave complexes that are inactive,
      and do not lose the 1,5-cyclooctadiene ligands under the hydrogenation
      conditions. Experiments to investigate this unexpected observation imply that it
      is of a steric, rather than an electronic, origin. Temperature and pressure
      effects on the conversions and enantioselectivities of these reactions had
      minimal effects for some alkenes, but profound effects for others. In one case,
      the enantioselectivities obtained at high-pressure/low-temperature conditions
      were opposite to those obtained under high-temperature/low-pressure conditions (
      64% enantiomeric excess versus +89% enantiomeric excess); a transformation from
      one prevalent mechanism to another is inferred from this. The studies of pressure
      dependence revealed that many reactions proceeded with high conversions, and
      optimal enantioselectivities in approximately 2 h when only 1 bar of hydrogen was
      used. Deuterium-labeling experiments provide evidence for other types of
      competing mechanisms that lead to D-incorporation at positions that do not
      correspond to direct addition to the double bond.

PMID- 12515513
TI  - (Phosphino)(aryl)carbenes: effect of aryl substituents on their stabilization
      mode.
AB  - A broad range of (phosphino)(aryl)carbenes, 1b-d, 10a,b, and 14a,b, were prepared
      by photolysis of their diazo precursors. The influence of the steric and
      electronic properties of the aryl ring on the structure and stability of these
      carbenes was studied both experimentally and theoretically. Among the different
      stabilization modes investigated, those featuring an acceptor as well as a
      spectator aryl substituent result in stable or at least persistent carbenes that
      could be completely characterized by classical spectroscopic methods. In marked
      contrast, the new substitution pattern featuring a donor aryl ring results in a
      very fleeting carbene.

PMID- 12515514
TI  - Experimental and theoretical characterization of the 3,5-didehydrobenzoate anion:
      a negatively charged meta-benzyne.
AB  - A negatively charged analogue of meta-benzyne, 3,5-didehydrobenzoate, was
      synthesized in a Fourier transform ion cyclotron resonance mass spectrometer, and
      its reactivity was compared to that of the same ion generated previously in a
      flowing afterglow apparatus and to its positively charged cousin, N-(3,5
      didehydrophenyl)-3-fluoropyridinium. 3,5-Didehydrobenzoate was found to react as
      a nucleophile with electrophilic reagents. In contrast, N-(3,5-didehydrophenyl)-3
      fluoropyridinium does not react with the same electrophilic reagents but reacts
      instead with nucleophilic reagents. Neither ion is able to abstract hydrogen
      atoms from typical hydrogen atom donors. The absence of any radical reactivity
      for these meta-benzynes is consistent with predictions that radical reactions of
      singlet biradicals should be hindered as compared to their monoradical
      counterparts. High-level calculations predict that the carboxylate moiety does
      not significantly perturb the singlet-triplet splitting of 3,5-didehydrobenzoate
      relative to the parent meta-benzyne.

PMID- 12515515
TI  - DNA sequence context and multiplex hybridization reactions: melting studies of
      heteromorphic duplex DNA complexes.
AB  - Heteromorphic hybrid duplex DNA complexes are duplex states, other than perfectly
      matched duplexes, that can form when single strands comprising several different
      perfectly matched duplexes are simultaneously present in solution. Such cross
      hybridization "side reactions" are of particular nuisance in multiplex reaction
      schemes, where many strands are designed to hybridize in parallel fashion with
      only their corresponding perfect complement strand. Relative to the perfect match
      duplexes, the sequence dependent features of these heteromorphic duplex states
      and their thermodynamic stability are an important consideration for multiplex
      hybridization reaction design. We have measured absorbance versus temperature
      melting curves and performed differential scanning calorimetry measurements on
      various mixtures of eight different 24 base single strands. When perfect
      complementary pairs of strands are mixed in single reactions, four perfectly
      matched duplexes form. When mixtures of strands that are not perfectly matched
      are prepared and analyzed, melting transitions for cross-hybridization are
      observed along with significant hyperchromicity changes. This is indicative of a
      melting hybrid, heteromorphic duplex states formed from two nonperfectly matched
      strands. In addition, when both the perfectly matched and noncomplementary
      strands are mixed together (in multiplex hybridization reactions) at molar ratios
      of 1:1, 3:1, and 1:3, evidence of perfect duplex and heteromorphic duplex
      complexes is found in all cases. A new analytical tool for considering
      heterogeneous, duplex complexes in multiplex hybridization mixtures is presented
      and employed to interpret the acquired melting data.

PMID- 12515516
TI  - Kinetic and thermodynamic acidities of substituted 1-benzyl-1-methoxy-2
      nitroethylenes. Strong reduction of the transition state imbalance compared to
      other nitroalkanes.
AB  - Acidity constants of six substituted 1-benzyl-1-methoxy-2-nitroethylenes (2-Z
      with Z = m-NO(2), m-CF(3), m-Cl, H, p-Me, p-MeO) and their respective nitronic
      acids were determined in 50% DMSO-50% water (v/v) at 20 degrees C. Kinetic data
      were obtained on the reversible deprotonation of all six 2-Z by OH(-) and
      piperidine and on the reversible deprotonation of 2-NO(2)() by piperazine, 1-(2
      hydroxyethyl)piperazine, and morpholine in the same solvent. These data allowed a
      determination of the Bronsted coefficients alpha (dependence on acidity of 2-Z)
      and beta (dependence on amine basicity). The fact that alpha > beta indicates the
      presence of a transition state imbalance which, however, is much smaller than
      that for the deprotonation of arylnitromethanes. The reasons for this reduction
      in the imbalance and their relevance to a recent study of the deprotonation of
      Fischer carbene complexes are discussed.

PMID- 12515517
TI  - Substituent effects on regioselective intramolecular oxidation of unactivated C-H
      bonds: stereoselective synthesis of substituted tetrahydropyrans.
AB  - Our previously reported intramolecular delta-selective C-H bond oxidation by
      dioxiranes, generated in situ from activated ketones, offers a novel approach to
      the synthesis of tetrahydropyrans. To synthesize substituted tetrahydropyrans in
      a stereoselective manner, we examined the effects of alkyl, nitrogen, and oxygen
      substituents at the alpha-, beta-, and gamma-sites of ketones on the
      stereoselectivities of intramolecular C-H bond oxidation reactions. Ketones 1-4
      with a methyl group at the alpha-, beta-, or gamma-site showed the
      diastereoselectivities that agreed with the trans/cis ratio predicted by
      considering steric interactions in the transition states. Furthermore, ketones 5
      and 6 carrying a bulky phthalimido group at the alpha- and the beta-sites,
      respectively, exhibited excellent stereoselectivity, each affording only one
      diastereomer. However, ketones 9 and 10 bearing beta-oxygen substituents gave
      reversed stereoselectivity as compared to those with beta-alkyl or nitrogen
      substituents, possibly because of the hydrogen bonding interaction in the
      transition state. For ketones 12 and 13, both bearing methyl and silyloxy groups,
      the hydrogen bonding interaction was probably more important than the steric
      effect on the diastereoselectivity of intramolecular oxidation of C-H bonds.

PMID- 12515518
TI  - Free radical-mediated aryl amination and its use in a convergent [3 + 2] strategy
      for enantioselective indoline alpha-amino acid synthesis.
AB  - The scope of aryl radical additions to the nitrogen of azomethines is described.
      Aryl, trifluoromethyl alkyl, and alpha,beta-unsaturated ketimines engage in
      regioselective aryl-nitrogen bond formation via 5-exo cyclizations of an aryl
      radical to azomethine nitrogen. Selectivity for carbon-nitrogen over carbon
      carbon bond formation is generally high (>95:5) and competes only with direct
      aryl radical reduction by stannane (0-10%). Alpha-ketoimines are a promising new
      class of carbon radical acceptors for which no competitive aryl radical reduction
      is observed. The reaction conditions are pH-neutral and are therefore among the
      mildest methods available for amination of an aromatic ring. The ketimines
      examined did not suffer from competitive reduction by stannane, offering an
      advantage over the use of diazo and azide functional groups as nitrogen sources
      for carbon radicals. The free radical-mediated aryl amination was sequenced with
      the O'Donnell phase transfer-catalyzed enantioselective alkylation strategy of
      glycinyl imine to provide either enantiomer of indoline alpha-amino acids with
      high ee. These new constrained phenyl alanine derivatives are now readily
      available for evaluation across a variety of applications.

PMID- 12515519
TI  - Low-temperature orientationally ordered structures of two-dimensional C60.
AB  - Orientationally ordered structures of two-dimensional (2D) C(60) at low
      temperature have been investigated theoretically and experimentally. Using total
      energy optimization with a phenomenological potential, we find the ground state
      is a close packed hexagonal lattice in which all the molecules have the same
      orientation. Several local minima of the potential energy surface are found to be
      associated with other 1 x 1 lattices as well as 2 x 2 lattices. The energies of
      the orientational domain boundaries of the 1x1 lattices are also computed, and
      two kinds of which yield negative values. A majority of these theoretical
      findings are confirmed by our low-temperature scanning tunneling microscopy study
      of a 2D C(60) array supported on a self-assembled monolayer.

PMID- 12515520
TI  - Highly selective binding of organometallic ruthenium ethylenediamine complexes to
      nucleic acids: novel recognition mechanisms.
AB  - We have investigated the recognition of nucleic acid derivatives by
      organometallic ruthenium(II) arene anticancer complexes of the type [(eta(6)
      arene)Ru(II)(en)X] where en = ethylenediamine, arene = biphenyl (Bip),
      tetrahydroanthracene (THA), dihydroanthracene (DHA), p-cymene (Cym) or benzene
      (Ben), X = Cl(-) or H(2)O using (1)H, (31)P and (15)N ((15)N-en) NMR
      spectroscopy. For mononucleosides, [(eta(6)-Bip)Ru(en)](2+) binds only to N7 of
      guanosine, to N7 and N1 of inosine, and to N3 of thymidine. Binding to N3 of
      cytidine was weak, and almost no binding to adenosine was observed. The
      reactivity of the various binding sites of nucleobases toward Ru at neutral pH
      decreased in the order G(N7) > I(N7) > I(N1), T(N3) > C(N3) > A(N7), A(N1).
      Therefore, pseudo-octahedral diamino Ru(II) arene complexes are much more highly
      discriminatory between G and A bases than square-planar Pt(II) complexes. Such
      site-selectivity appears to be controlled by the en NH(2) groups, which H-bond
      with exocyclic oxygens but are nonbonding and repulsive toward exocyclic amino
      groups of the nucleobases. For reactions with mononucleotides, the same pattern
      of site selectivity was observed, but, in addition, significant amounts of the 5'
      phosphate-bound species (40-60%) were present at equilibrium for 5'-TMP, 5'-CMP
      and 5'-AMP. In contrast, no binding to the phosphodiester groups of 3', 5'-cyclic
      GMP (cGMP) or cAMP was detected. Reactions with nucleotides proceeded via
      aquation of [(eta(6)-arene)Ru(en)Cl](+), followed by rapid binding to the 5'
      phosphate, and then rearrangement to give N7, N1, or N3-bound products. Small
      amounts of the dinuclear species, e.g., Ru-O(PO(3))GMPN7-Ru, Ru-O(PO(3))IMPN1-Ru,
      Ru-O(PO(3))TMPN3-Ru, Ru-N7IMPN1-Ru, and Ru-N7InoN1-Ru were also detected. In
      competitive binding experiments for [(eta(6)-Bip)Ru(en)Cl](+) with 5'-GMP versus
      5'-AMP or 5'-CMP or 5'-TMP, the only final adduct was [(eta(6)-Bip)Ru(en)(N7
      GMP)]. Ru-H(2)O species were more reactive than Ru-OH species. The presence of
      Cl(-) or phosphate in neutral solution significantly decreased the rates of Ru-N7
      binding through competitive coordination to Ru. In kinetic studies (pH 7.0, 298
      K, 100 mM NaClO(4)), the rates of reaction of cGMP with [(eta(6)
      arene)Ru(II)(en)X](n+) (X = Cl(-) or H(2)O) decreased in the order: THA > Bip >
      DHA >> Cym > Ben, suggesting that N7-binding is promoted by favorable arene
      purine hydrophobic interactions in the associative transition state. These
      findings have revealed that the diamine NH(2) groups, the hydrophobic arene, and
      the chloride leaving group have important roles in the novel mechanism of
      recognition of nucleic acids by Ru arene complexes, and will aid the design of
      more effective anticancer complexes, as well as new site-specific DNA reagents.

PMID- 12515521
TI  - The mandelamide keto-enol system in aqueous solution. Generation of the enol by
      hydration of phenylcarbamoylcarbene.
AB  - Flash photolysis of diazophenylacetamide in aqueous solution produced
      phenylcarbamoylcarbene, whose hydration generated a transient species that was
      identified as the enol isomer of mandelamide. This assignment is based on product
      identification and the shape of the rate profile for decay of the enol transient,
      through ketonization to its carbonyl isomer, as well as by the form of acid-base
      catalysis of and solvent isotope effects on the decay reaction. Rates of
      enolization of mandelamide were also determined, by monitoring hydrogen exchange
      at its benzylic position, and these, in combination with the ketonization rate
      measurements, gave the keto-enol equilibrium constant pK(E) = 15.88, the acidity
      constant of the enol ionizing as an oxygen acid, pQ(E)(a)= 8.40, and the acidity
      constant of the amide ionizing as a carbon acid pQ(K)(a)= 24.29. (These acidity
      constants are concentration quotients applicable at ionic strength = 0.10 M.)
      These results show the enol content and carbon acid strength of mandelamide, like
      those of mandelic acid and methyl mandelate, to be orders of magnitude less than
      those of simple aldehydes and ketones; this difference can be attributed to
      resonance stabilization of the keto isomers of mandelic acid and its ester and
      amide derivatives, through electron delocalization into their carbonyl groups
      from the oxygen and nitrogen substituents adjacent to these groups. The enol of
      mandelamide, on the other hand, again like the enols of mandelic acid and methyl
      mandelate, is a substantially stronger acid than the enols of simple aldehydes
      and ketones. This difference can be attributed to the electronegative nature of
      the oxygen and nitrogen substituents geminal to the enol hydroxyl group in the
      enols of mandelic acid and its derivatives; in support of this, the acidity
      constants of these enols correlate well with field substituent constants of these
      geminal groups.

PMID- 12515522
TI  - Energy transfer on the MgO surface, monitored by UV-induced H2 chemisorption.
AB  - Surface anions on edges (4-coordinated = 4C) and on corners (3-coordinated = 3C)
      of cubic MgO nanoparticles exhibit UV resonance absorptions around 5.5 and 4.6
      eV, respectively. After monochromatic excitation of either site the electron
      paramagnetic resonance (EPR) spectrum exhibits exclusively signal components
      related to 3-coordinated O- radicals (O-(3C), electron hole centers), which are
      perfectly bleached by H(2) addition. The disappearance of the O-(3C) EPR signal
      components is paralleled by a depletion of the UV resonance absorption of the 3
      coordinated O(2-) only and the appearance of one single band in the OH stretching
      region of the IR spectrum. Obviously the sites of UV excitation and subsequent UV
      induced surface reaction with H(2) are not the same. This may coherently be
      explained in terms of mobility of the exciton (O(2-)(4C)* or--after ionization-
      of the corresponding electron hole O-(4C) along the edge where it was created.
      Finally the mobile state is trapped at a corner site where the O(3C)H group is
      formed.

PMID- 12515523
TI  - Syntheses, crystallographic/computational characterizations, and reactions of the
      first 10-vertex arachno- and nido-phosphamonocarbaboranes.
AB  - A synthetic sequence involving the initial reaction of a substituted phosphorus
      dihalide (RPCl(2), R = CH(3), C(6)H(5)) with the arachno-CB(8)H(13)(-) (1-)
      monoanion followed by an in situ dehydrohalogenation reaction initiated by Proton
      Sponge, resulted in phosphorus cage insertion to yield the first 10-vertex
      arachno- and nido-phosphamonocarbaboranes, exo-6-R-arachno-6,7-PCB(8)H(12) (2a,
      2b) and PSH(+)6-R-nido-6,9-PCB(8)H(9)(-) (PSH+3a-, PSH+3b-) (R = C(6)H(5) (a),
      CH(3) (b)). Alternatively, 2a and 2b were synthesized in high yield as the sole
      product of the reaction of the arachno-4-CB(8)H(12)(2-) (1(2-)) dianion with
      RPCl(2). Crystallographic determinations of PSH+3a- and PSH+3b- in conjunction
      with DFT/GIAO computational studies of the anions have confirmed the expected
      nido cage framework based on an octadecahedron missing the six-coordinate vertex.
      DFT/GIAO computational studies have also shown that while the gross cage
      geometries of the exo-6-R-arachno-6,7-PCB(8)H(12) compounds 2a and 2b resemble
      the known isoelectronic arachno-6,9-SCB(8)H(12), the phosphorus and carbon atoms
      are in thermodynamically unfavorable adjacent positions on the six-membered
      puckered face. They also each have an endo-hydrogen at the P6-position arising
      from proton transfer to the basic phosphorus during the cage-insertion reaction.
      Possible stepwise reaction pathways that can account for the formation of both
      the arachno and nido products are discussed. Deprotonation of 2a and 2b resulted
      in the formation of their corresponding conjugate monoanions, 6-R-arachno-6,7
      PCB(8)H(11)(-) (2a-, 2b-), in which the proton that had been attached to the P6
      atom was removed. Reactions of 2a- with O(2), S(8), BH(3).THF, or Br(2) further
      demonstrated the basicity of the P6-phosphorus yielding the new arachno
      substituted compounds, endo-6-O-exo-6-(C(6)H(5))-arachno-6,7-PCB(8)H(11)(-) (4a
      ), endo-6-S-exo-6-(C(6)H(5))-arachno-6,7-PCB(8)H(11)(-) (5a-), endo-6-BH(3)-exo-6
      (C(6)H(5))-arachno-6,7-PCB(8)H(11)(-) (6a-), and endo-6-Br-exo-6-(C(6)H(5))
      arachno-6,7-PCB(8)H(11) (7a), respectively, in which the O, S, BH(3), and Br
      substituents are bound to the phosphorus at the endo position.

PMID- 12515524
TI  - Syntheses and structural characterizations of endo-eta(1)-, exo-eta(1)-, eta(4)-,
      eta(5)-, and eta(6)-metallaphosphamonocarbaborane complexes derived from a
      versatile new polyborane ligand: exo-6-R-arachno-6,7-PCB(8)H(12).
AB  - Deprotonation of the phosphamonocarbaborane, exo-6-R-arachno-6,7-PCB(8)H(12) (R =
      Ph 1a or Me 1b), yields exo-6-R-arachno-6,7-PCB(8)H(11)(-), which when reacted
      with appropriate transition-metal reagents affords new
      metallaphosphamonocarbaborane complexes in which the metals adopt endo-eta(1),
      exo-eta(1), eta(4), eta(5), or eta(6) coordination geometries bonded to the
      formal R-arachno-PCB(8)H(11)(-), R-arachno-PCB(8)H(10)(2-), R-arachno
      PCB(8)H(9)(3-), or R-nido-PCB(8)H(9)(-) ligands. The reaction of exo-6-(C(6)H(5))
      arachno-6,7-PCB(8)H(11)(-) (1a-) with Mn(CO)(5)Br generated the eta(1)-sigma
      product exo-6-[Mn(CO)(5)]-endo-6-(C(6)H(5))-arachno-6,7-PCB(8)H(11) (2) having
      the [Mn(CO)(5)] fragment in the thermodynamically favored exo position at the P6
      cage atom. On the other hand, reaction of 1a- with (eta(5)-C(5)H(5))Fe(CO)(2)I
      resulted in the formation of two products, an eta(1)-sigma complex endo-6
      [(eta(5)-C(5)H(5))Fe(CO)(2)]-exo-6-(C(6)H(5))-arachno-6,7-PCB(8)H(11) (3) having
      the (eta(5)-C(5)H(5))Fe(CO)(2) fragment attached at the endo-P6 position and an
      eta(6)-closo complex, 1-(eta(5)-C(5)H(5))-2-(C(6)H(5))-closo-1,2,3-FePCB(8)H(9)
      (4a). Rearrangement of the endo-compound 3 to its exo-isomer 5 was observed upon
      photolysis of 3. Synthesis of the methyl analogue of 4a, 1-(eta(5)-C(5)H(5))-2
      CH(3)-closo-1,2,3-FePCB(8)H(9) (4b), along with a double-insertion product, 1
      CH(3)-2,3-(eta(5)-C(5)H(5))(2)-2,3,1,7-Fe(2)PCB(8)H(9) (6), containing two iron
      atoms eta(5)-coordinated to a formal R-arachno-PCB(8)H(9)(3-), was achieved by
      reaction of exo-6-CH(3)-arachno-6,7-PCB(8)H(11)(-) (1b-) with FeCl(2) and
      Na(+)C(5)H(5)(-). Complexes 4a and 4b can be considered ferrocene analogues, in
      which an Fe(II) is sandwiched between C(5)H(5)(-) and 6-R-nido-6,9-PCB(8)H(9)(-)
      anions. Reaction of exo-6-(C(6)H(5))-arachno-6,7-PCB(8)H(11)(-) (1a-) with cis
      dichlorobis(triphenylphosphine)platinum (II) afforded two compounds, an eta(1)
      sigma complex with the metal fragment again in the endo-P6 position, endo-6-[cis
      (Ph(3)P)(2)PtCl]-exo-6-(C(6)H(5))-arachno-6,7-PCB(8)H(11) (7) and an eta(4)
      complex, 7-(C(6)H(5))-11-(Ph(3)P)(2)-nido-11,7,8-PtPCB(8)H(10) (8) containing the
      formal R-arachno-PCB(8)H(10)(2)(-) anion. The structures of compounds 2, 3, 4a,
      4b, 6, 7, and 8 were crystallographically confirmed.

PMID- 12515525
TI  - Design of novel inorganic-organic hybrid materials based on iron-chloranilate
      mononuclear complexes: characteristics of hydrogen-bond-supported layers toward
      the intercalation of guests.
AB  - Novel intercalation compounds constructed from the common two-dimensional
      hydrogen-bond-supported layers and functional guests
      [(H(0.5)phz)(2)[Fe(CA)(2)(H(2)O)(2)].2H(2)O](n)(1),
      ([Fe(Cp)(2)][Fe(CA)(2)(H(2)O)(2)])(n)(2),
      ([Fe(Cp*)(2)][Fe(CA)(2)(H(2)O)(2)])(n)(3), and
      [(TTF)(2)[Fe(CA)(2)(H(2)O)(2)]](n)(4) (H(2)CA = chloranilic acid, phz =
      phenazine, [Fe(Cp)(2)] = ferrocene, [Fe(Cp*)(2)] = decamethylferrocene, TTF =
      tetrathiafulvalene) are described. The guest cations are introduced between the
      ([Fe(CA)(2)(H(2)O)(2)](m-))(l) layers by electrostatic (1-4) and pi-pi stacking
      (3, 4) interactions. [Fe(Cp*)(2)](+) cations in 3 are stacked on each other
      making tilted columns which are included in the channel created by the chlorine
      atoms of CA(2-) dianions. TTF cations in 4 are stacked face to face with two
      types of S...S distances (type A; 3.579(3) A, and type B; 3.618(3) A) making a
      columnar structure. The TTF cations in the stacked column have a head-to-tail
      arrangement with respect to the iron-chloranilate layer. Mossbauer spectroscopy
      suggests that [Fe(CA)(2)(H(2)O)(2)](m-) anion in 3 is consistent with high-spin
      (S = 5/2) iron(III) ions and [Fe(Cp*)(2)](+) in the low-spin (S = 1/2) iron(III)
      ions. In 4, Mossbauer spectroscopy shows high-spin iron(II) ions (IS = 1.10 mm.s(
      1) and QS = 1.66 mm.s(-1) at 297 K) and high-spin iron(III) ions (IS = 0.42 mm.s(
      1) and QS = 1.27 mm.s(-1) at 297 K), suggesting that the anionic layer of iron
      chloranilate has a valence-trapped mixed-valence state. At the temperature range
      of 77-300 K, the compounds 1, 2, and 3 are EPR silent, whereas the EPR spectrum
      of 4 shows two types of signals with g = 2.008 indicating the radical form of
      TTF.

PMID- 12515526
TI  - Solvent coordination in gas-phase [Mn.(H(2)O)(n)](2+) and [Mn.(ROH)(n)](2+)
      complexes: theory and experiment.
AB  - An experimental gas-phase study of the intensities and fragmentation patterns of
      [Mn.(H(2)O)(n)](2+) and [Mn.(ROH)(n)](2+) complexes shows the combinations
      [Mn.(H(2)O)(4)](2+) and [Mn.(ROH)(4)](2+) to be stable. Evidence in complexes
      involving the alcohols methanol, ethanol, 1-propanol, and 2-propanol favors
      preferential fragmentation to [Mn.(ROH)(4)](2+), whereas the fragmentation data
      for water is less clear. Supporting density functional calculations show that
      both [Mn.(H(2)O)(4)](2+) and [Mn.(MeOH)(4)](2+) adopt stable tetrahedral
      configurations, similar to those proposed for biochemical systems where solvent
      availability and coordination is restricted. Calculated incremental binding
      energies show a gradual decline on going from one to six solvent molecules, with
      a step occurring between four and five molecules. The addition of further solvent
      molecules to the stable [Mn.(MeOH)(4)](2+) unit shows a preference for
      [Mn.(MeOH)(4)(MeOH)(1,2)](2+) structures, where the extra molecules occupy
      hydrogen-bonded sites in the form of a secondary solvation shell. Very similar
      behavior is seen on the part of water. As part of an analysis of the experimental
      data, the calculations have explored the influence different spins states of
      Mn(2+) have on solvent geometry. It is concluded that the experimental
      observations are best reproduced when the central Mn(2+) ion is in the high-spin
      (6)S ground state. The results are also considered in terms of the biochemical
      activity of Mn(2+) where the ion is capable of isomorphous substitution with
      Zn(2+), which itself exhibits a preference for tetrahedral coordination.

PMID- 12515527
TI  - Kinetic isotope effects for concerted multiple proton transfer: a direct dynamics
      study of an active-site model of carbonic anhydrase II.
AB  - The rate constant of the reaction catalyzed by the enzyme carbonic anhydrase II,
      which removes carbon dioxide from body fluids, is calculated for a model of the
      active site. The rate-determining step is proton transfer from a zinc-bound water
      molecule to a histidine residue via a bridge of two or more water molecules. The
      structure of the active site is known from X-ray studies except for the number
      and location of the water molecules. Model calculations are reported for a system
      of 58 atoms including a four-coordinated zinc ion connected to a methylimidazole
      molecule by a chain of two waters, constrained to reproduce the size of the
      active site. The structure and vibrational force field are calculated by an
      approximate density functional treatment of the proton-transfer step at the Self
      Consistent-Charge Density Functional Tight Binding (SCC-DFTB) level. A single
      transition state is found indicating concerted triple proton transfer. Direct
      dynamics calculations for proton and deuteron transfer and combinations thereof,
      based on the Approximate Instanton Method and on Variational Transition State
      Theory with Tunneling Corrections, are in fair agreement and yield rates that are
      considerably higher and kinetic isotope effects (KIEs) that are somewhat higher
      than experiment. Classical rate constants obtained from Transition State Theory
      are smaller than the quantum values but the corresponding KIEs are five times
      larger. For multiple proton transfer along water bridges classical KIEs are shown
      to be generally larger than quantum KIEs, which invalidates the standard method
      to distinguish tunneling and over-barrier transfer. In the present case, a three
      way comparison of classical and quantum results with the observed data is
      necessary to conclude that proton transfer along the bridge proceeds by
      tunneling. The results suggest that the two-water bridge is present in low
      concentrations but makes a substantial contribution to proton transport because
      of its high efficiency. Bridging structures containing more water molecules may
      have lower energies but are expected to be less efficient. The observed
      exponential dependence of the KIEs on the deuterium concentration in H(2)O/D(2)O
      mixtures implies concerted transfer and thus rules out substantial contributions
      from structures that lead to stepwise transfer via solvated hydronium ions, which
      presumably dominate proton transfer in less efficient carbonic anhydrase
      isozymes.

PMID- 12515528
TI  - Time-dependent density functional theory (TDDFT) study of the excited charge
      transfer state formation of a series of aromatic donor-acceptor systems.
AB  - Singlet excitation energy calculations for a series of acceptor para-substituted
      N,N-dimethyl-anilines that are dual (4-(N,N-dimethylamino)benzonitrile, 4DMAB-CN,
      4-(N,N-dimethylamino)benzaldhyde, 4DMAB-CHO, 1-methyl-7-cyano-2,3,4,5-tetrahydro
      1H-1-benzazepine, NMC7) and nondual (4-aminobenzonitrile, 4AB-CN, 3-(N,N
      dimethylamino)benzonitrile, 3DMAB-CN, and 4-nitro(N,N-dimethyl) aniline, 4DMAB
      NO(2)) fluorescent have been performed using time-dependent density functional
      theory (TDDFT). The B3LYP and MPW1PW91 functionals with a 6-311+G(2d,p) (Bg)
      basis set have been used to compute excitation energies. Ground-state geometries
      were optimized using density functional theory (DFT) with both B3LYP and MPW1PW91
      functionals combined with a 6-31G(d) basis set. For most of the molecules
      presented in this study, potential energy surfaces have been computed according
      to the coordinates related to the three following mechanisms proposed in the
      literature: twisting, wagging, and planar intramolecular charge transfer (ICT).
      Comparison of the three models for the different molecules leads to the
      conclusion that only the twisting ICT model is able to explain the low frequency,
      strongly solvent-dependent energy band present in the fluorescence spectra.
      According to this model, the 4AB-CN molecule is calculated to be nondual
      fluorescent in agreement with the experimental spectra. The single band observed
      in the fluorescence spectra of TMAB-CN (4-(N,N-dimethylamino)-3,5
      (dimethyl)benzonitrile) is due to a large stabilization of the charge-transfer
      excited state along the twisting coordinate. The nondual fluorescence of the
      4DMAB-NO(2) molecule is explained by the same mechanism. In the case of 3DMAB-CN,
      the single observed emission, which is solvent-dependent, has been assigned to
      the lowest charge-transfer excited state. The dual fluorescence of 4DMAB-CN and
      4DMAB-CHO is explained within the twisting ICT model by a double mechanism
      (already proposed by Serrano et al.: Serrano-Andres, L.; Merchan, M.; Roos, B.
      J.; Lindh, R. J. Am. Chem. Soc. 1995, 117, 3189) that involves the presence of
      two low-lying states close enough in energy. The observation of dual fluorescence
      in NMC7, that has been one of the origins of the planar ICT model put forward by
      Zachariasse et al. (Zachariasse, K.; van der Haar, T.; Hebecker, A.; Leinhos, U.;
      Kuhnle, W. Pure Appl. Chem. 1993, 65, 1745), could be fully understood by a
      double mechanism within the twisting ICT model. Within the set of investigated
      molecules, our calculations confirm that the twisting ICT model is the only
      mechanism acceptable to explain the dual and nondual fluorescence phenomenon. Our
      calculations are in complete agreement with experimental data.

PMID- 12515529
TI  - X- and W-band EPR and Q-band ENDOR studies of the flavin radical in the Na+ 
      translocating NADH:quinone oxidoreductase from Vibrio cholerae.
AB  - Na(+)-NQR is the entry point for electrons into the respiratory chain of Vibrio
      cholerae. It oxidizes NADH, reduces ubiquinone, and uses the free energy of this
      redox reaction to translocate sodium across the cell membrane. The enzyme is a
      membrane complex of six subunits that accommodates a 2Fe-2S center and several
      flavins. Both the oxidized and reduced forms of Na(+)-NQR exhibit a radical EPR
      signal. Here, we present EPR and ENDOR data that demonstrate that, in both forms
      of the enzyme, the radical is a flavin semiquinone. In the oxidized enzyme, the
      radical is a neutral flavin, but in the reduced enzyme the radical is an anionic
      flavin, where N(5) is deprotonated. By combining results of ENDOR and
      multifrequency continuous wave EPR, we have made an essentially complete
      determination of the g-matrix and all major nitrogen and proton hyperfine
      matrices. From careful analysis of the W-band data, the full g-matrix of a flavin
      radical has been determined. For the neutral radical, the g-matrix has
      significant rhombic character, but this is significantly decreased in the anionic
      radical. The out-of-plane component of the g-matrix and the nitrogen hyperfine
      matrices are found to be noncoincident as a result of puckering of the pyrazine
      ring. Two possible assignments of the radical signals are considered. The neutral
      and anionic forms of the radical may each arise from a different flavin cofactor,
      one of which is converted from semiquinone to flavohydroquinone, while the other
      goes from flavoquinone to semiquinone, at almost exactly the same redox
      potential, during reduction of the enzyme. Alternatively, both forms of the
      radical signal may arise from a single, extremely stable, flavin semiquinone,
      which becomes deprotonated upon reduction of the enzyme.

PMID- 12515530
TI  - Coverage effects and the nature of the metal-sulfur bond in S/Au(111): high
      resolution photoemission and density-functional studies.
AB  - The bonding of sulfur to surfaces of gold is an important subject in several
      areas of chemistry, physics, and materials science. Synchrotron-based high
      resolution photoemission and first-principles density-functional (DF) slab
      calculations were used to study the interaction of sulfur with a well-defined
      Au(111) surface and polycrystalline gold. Our experimental and theoretical
      results show a complex behavior for the sulfur/Au(111) interface as a function of
      coverage and temperature. At small sulfur coverages, the adsorption of S on fcc
      hollow sites of the gold substrate is energetically more favorable than
      adsorption on bridge or a-top sites. Under these conditions, S behaves as a weak
      electron acceptor but substantially reduces the density-of-states that gold
      exhibits near the Fermi edge. As the sulfur coverage increases, there is a
      weakening of the Au-S bonds (with a simultaneous reduction in the Au --> S charge
      transfer and a modification in the S sp hybridization) that facilitates changes
      in adsorption site and eventually leads to S-S bonding. At sulfur coverages above
      0.4 ML, S(2) and not atomic S is the more stable species on the gold surface.
      Formation of S(n)(n > 2) species occurs at sulfur coverages higher than a
      monolayer. Very similar trends were observed for the adsorption of sulfur on
      polycrystalline surfaces of gold. The S atoms bonded to Au(111) display a unique
      mobility/reactivity not seen on surfaces of early or late transition metals.

PMID- 12515531
TI  - How constant are Ritchie's "constant selectivity relationships"? A general
      reactivity scale for n-, pi-, and sigma-nucleophiles.
AB  - The kinetics of 82 reactions of benzhydrylium ions (Ar(2)CH(+)) with n
      nucleophiles has been determined at 20 degrees C. Evaluation by the equation log
      k = s(N + E) delivered the reactivity parameters N and s for 15 n-nucleophiles
      (water, hydroxide, amines, etc.). All nucleophiles except water (s = 0.89) and (
      )SCH(2)CO(2)(-) (s = 0.43) have closely similar slope parameters (0.52 < s <
      0.71), indicating that the reactions of most n-nucleophiles approximately follow
      Ritchie's constant selectivity relationship (s = constant). The different slope
      parameter for water is recognized as the main reason for the deviations from the
      Ritchie relationship reported in 1986. Correlation analysis of the rate constants
      for the reactions of benzhydrylium ions with the n-nucleophiles (except H(2)O) on
      the basis of Ritchie's equation log k = N(+) + log k(0) yields a statistically
      validated set of N(+) parameters for Ritchie-type nucleophiles and log k(0)
      parameters for benzhydrylium ions. The N and s parameters of the n-nucleophiles
      derived from their reactions with benzhydrylium ions were combined with
      literature data for the reactions of these nucleophiles with other carbocations
      to yield electrophilicity parameters E for tritylium, tropylium, and xanthylium
      ions. While the E parameters for tropylium and xanthylium ions appear to be
      generally applicable, it is demonstrated that the E parameters of tritylium ions
      can be used to predict reactivities toward n-nucleophiles as well as hydride
      transfer rate constants but not rates for the reactions of tritylium ions with pi
      nucleophiles. It is now possible to merge the large data sets determined by
      Ritchie and others with our kinetic data and present a nucleophilicity scale
      comprising n- (e.g., amines), pi- (e.g., alkenes and arenes), and sigma
      nucleophiles (e.g., hydrides).

PMID- 12515532
TI  - Photodetachment of zwitterions: probing intramolecular coulomb repulsion and
      attraction in the gas phase using pyridinium dicarboxylate anions.
AB  - Zwitterions are critically important in many biological transformations and are
      used in numerous chemical processes. The consequences of electrostatic effects on
      reactivity and physical properties, however, are largely unknown. In this work,
      we report the results of negative ion photoelectron spectra of nine isomeric
      pyridinium dicarboxylate zwitterions and three nonzwitterionic
      methoxycarbonylpyridine carboxylate isomers (-O(2)CPyrCO(2)CH(3)). Information
      about the intramolecular electrostatic interactions was directly obtained from
      the photoelectron spectra. The adiabatic and vertical detachment energies were
      measured and understood in terms of intramolecular Coulombic forces. Calculations
      at the B3LYP and CCSD(T) level were performed and compared to the experimental
      electron binding energies. Structures, relative stabilities, and the electron
      detachment sites also were obtained from the calculations.

PMID- 12515534
TI  - The LOV domain family: photoresponsive signaling modules coupled to diverse
      output domains.
AB  - For single-cell and multicellular systems to survive, they must accurately sense
      and respond to their cellular and extracellular environment. Light is a nearly
      ubiquitous environmental factor, and many species have evolved the capability to
      respond to this extracellular stimulus. Numerous photoreceptors underlie the
      activation of light-sensitive signal transduction cascades controlling these
      responses. Here, we review the properties of the light, oxygen, or voltage (LOV)
      family of blue-light photoreceptor domains, a subset of the Per-ARNT-Sim (PAS)
      superfamily. These flavin-binding domains, first identified in the higher-plant
      phototropins, are now shown to be present in plants, fungi, and bacteria.
      Notably, LOV domains are coupled to a wide array of other domains, including
      kinases, phosphodiesterases, F-box domains, STAS domains, and zinc fingers, which
      suggests that the absorption of blue light by LOV domains regulates the activity
      of these structurally and functionally diverse domains. LOV domains contain a
      conserved molecular volume extending from the flavin cofactor, which is the locus
      for light-driven structural change, to the molecular surface. We discuss the role
      of this conserved volume of structure in LOV-regulated processes.

PMID- 12515535
TI  - Dissection of binding interactions in the complex between the anti-lysozyme
      antibody HyHEL-63 and its antigen.
AB  - Alanine-scanning mutagenesis, X-ray crystallography, and double mutant cycles
      were used to characterize the interface between the anti-hen egg white lysozyme
      (HEL) antibody HyHEL-63 and HEL. Eleven HEL residues in contact with HyHEL-63 in
      the crystal structure of the antigen-antibody complex, and 10 HyHEL-63 residues
      in contact with HEL, were individually truncated to alanine in order to determine
      their relative contributions to complex stabilization. The residues of HEL
      (Tyr20, Lys96, and Lys97) most important for binding HyHEL-63 (Delta G(mutant) -
      Delta G(wild type) > 3.0 kcal/mol) form a contiguous patch at the center of the
      surface contacted by the antibody. Hot spot residues of the antibody (Delta Delta
      G > 2.0 kcal/mol) are organized in two clusters that juxtapose hot spot residues
      of HEL, resulting in energetic complementarity across the interface. All
      energetically critical residues are centrally located, shielded from solvent by
      peripheral residues that contribute significantly less to the binding free
      energy. Although HEL hot spot residues Lys96 and Lys97 make similar interactions
      with antibody in the HyHEL-63/HEL complex, alanine substitution of Lys96 results
      in a nearly 100-fold greater reduction in affinity than the corresponding
      mutation in Lys97. To understand the basis for this marked difference, we
      determined the crystal structures of the HyHEL-63/HEL Lys96Ala and HyHEL-63/HEL
      Lys97Ala complexes to 1.80 and 1.85 A resolution, respectively. Whereas
      conformational changes in the proteins and differences in the solvent networks at
      the mutation sites appear too small to explain the observed affinity difference,
      superposition of free HEL in different crystal forms onto bound HEL in the wild
      type and mutant HyHEL-63/HEL complexes reveals that the side-chain conformation
      of Lys96 is very similar in the various structures, but that the Lys97 side chain
      displays considerable flexibility. Accordingly, a greater entropic penalty may be
      associated with quenching the mobility of the Lys97 than the Lys96 side chain
      upon complex formation, reducing binding. To further dissect the energetics of
      specific interactions in the HyHEL-63/HEL interface, double mutant cycles were
      constructed to measure the coupling of 13 amino acid pairs, 11 of which are in
      direct contact in the crystal structure. A large coupling energy, 3.0 kcal/mol,
      was found between HEL residue Lys97 and HyHEL-63 residue V(H)Asp32, which form a
      buried salt bridge surrounded by polar residues of the antigen. Thus, in contrast
      to protein folding where buried salt bridges are generally destabilizing, salt
      bridges in protein-protein interfaces, whose residual composition is more
      hydrophilic than that of protein interiors, may contribute significantly to
      complex stabilization.

PMID- 12515536
TI  - Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal
      and mutant CHO cells defective in cholesterol metabolism.
AB  - The effect of the cholesterol content of the plasma membrane on the intracellular
      concentration of oxygen in Chinese hamster ovary (CHO) cells and their mutants
      was investigated by EPR oximetry. Total and free cholesterol content was
      significantly higher in 25 RA CHO cells as compared to wild-type and M 19 CHO
      cells, with most of the free cholesterol in normal and mutant CHO cells located
      in the plasma membrane. The plasma membrane cholesterol content also was altered
      by various biochemical means, and the effect on the oxygen gradient was studied.
      Comparing the three cell lines, the gradient was larger with increased content of
      cholesterol in the plasma cell membrane. This result also is supported by an
      additional increase in the oxygen gradients with the incorporation of additional
      cholesterol in the plasma membrane and a decrease in the oxygen gradient when the
      cholesterol was depleted from the plasma membrane. The results indicate that the
      concentration of cholesterol in the plasma membrane can be an important factor
      for the magnitude of the oxygen gradient observed across the cell membrane.

PMID- 12515537
TI  - Mutational analysis of a sequence-specific ssDNA binding lupus autoantibody.
AB  - 11F8 is a murine anti-ssDNA monoclonal autoantibody isolated from a lupus prone
      autoimmune mouse. This mAb binds sequence specifically, and prior studies have
      defined the thermodynamic and kinetic basis for sequence-specific recognition of
      ssDNA (Ackroyd, P. C., et al. (2001) Biochemistry 40, 2911-2922; Beckingham, J.
      A. and Glick, G. D. (2001) Bioorg. Med. Chem. 9, 2243-2252). Here we present
      experiments designed to identify the residues on 11F8 that mediate sequence
      specific, noncognate, and nonspecific recognition of ssDNA and their contribution
      to the overall binding thermodynamics. Site-directed mutagenesis of an 11F8
      single-chain construct reveals that six residues within the complementarity
      determining regions of 11F8 account for ca. 80% of the binding free energy and
      that there is little cooperativity between these residues. Germline-encoded
      aromatic and hydrophobic side chains provides the basis for nonspecific
      recognition of single-stranded thymine nucleobases. Sequence-specific recognition
      is controlled by a tyrosine in the heavy chain along with a somatically mutated
      arginine residue. Our data show that the manner in which 11F8 achieves sequence
      specific recognition more closely resembles RNA-binding proteins such as U1A than
      other types of nucleic acid binding proteins. In addition, comparing the primary
      sequence of 11F8 with clonally related antibodies that differ by less than five
      amino acids suggests that somatic mutations which confer sequence specificity may
      be a feature that distinguishes glomerulotrophic pathogenic anti-DNA from those
      that are benign.

PMID- 12515538
TI  - Caveolin scaffolding region and the membrane binding region of SRC form lateral
      membrane domains.
AB  - Formation of domains by the membrane binding motifs of caveolin and src were
      studied in large unilamellar vesicles using fluorescence digital imaging
      microscopy. Caveolin, a major structural protein of caveolae, contains a
      scaffolding region (residues 82-101) that contributes to the binding of the
      protein to the plasma membrane. A caveolin peptide (82-101) corresponding to this
      scaffolding region induced the formation of membrane domains enriched in the
      acidic lipids phosphatidylserine and phosphatidylinositol-4,5-bisphosphate.
      Cholesterol, another predominant component of caveolae, was also enriched in
      these domains. Caveolae also contain many different signaling molecules including
      src family tyrosine kinases. Src proteins bind to the plasma membrane via a N
      terminal myristate chain and a cluster of basic residues that can interact
      electrostatically with negatively charged lipids. A peptide corresponding to the
      src membrane binding motifs (residues myr-2-19) sequestered acidic lipids into
      lateral membrane domains. Both the src and the caveolin peptides colocalized
      together with acidic lipids in the domains. Control experiments show the domains
      are not the result of vesicle aggregation. Two-photon fluorescence correlation
      spectroscopy experiments suggest diffusion in the domains was slower, but the
      domains were dynamic. Protein kinase C phosphorylated src in its N-terminal
      membrane binding region; however, the caveolin scaffolding peptide inhibited this
      activity. Consequently, protein-induced membrane domains may affect cell
      signaling by organizing signal transduction components within the membrane and
      changing reaction rates.

PMID- 12515539
TI  - Relaxation-based structure refinement and backbone molecular dynamics of the
      dynein motor domain-associated light chain.
AB  - The light chain 1 (LC1) polypeptide is a member of the leucine-rich repeat
      protein family and binds at or near the ATP hydrolytic site within the motor
      domain of the gamma heavy chain from Chlamydomonas outer arm dynein. It consists
      of an N-terminal helix, a central barrel formed from six leucine-rich repeats
      that fold as beta beta alpha units, and a C-terminal helical domain that
      protrudes from the main axis defined by the leucine-rich repeats. Interaction
      with the gamma heavy chain is likely mediated through a hydrophobic patch on the
      larger beta sheet face, and the C-terminal region is predicted to insert into the
      dynein ATP hydrolytic site. Here we have used 1H-15N heteronuclear relaxation
      measurements obtained at 500 and 600 MHz to refine and validate the LC1 solution
      structure. In this refined structure, the C-terminal helix is significantly
      reoriented by more than 20 degrees as compared to the control and provides a more
      precise understanding of the potential regulatory role of this domain. We also
      employed the refined structure to perform a dynamic analysis of LC1 using the 600
      MHz data set. These results, which were cross validated using the 500 MHz data
      set, strongly support identification of the predicted LC1 binding surfaces and
      provide additional insight into the interaction mechanisms of leucine-rich repeat
      proteins.

PMID- 12515540
TI  - A model of structure and catalysis for ketoreductase domains in modular
      polyketide synthases.
AB  - A putative catalytic triad consisting of tyrosine, serine, and lysine residues
      was identified in the ketoreductase (KR) domains of modular polyketide synthases
      (PKSs) based on homology modeling to the short chain dehydrogenase/reductase
      (SDR) superfamily of enzymes. This was tested by constructing point mutations for
      each of these three amino acid residues in the KR domain of module 6 of the 6
      deoxyerythronolide B synthase (DEBS) and determining the effect on ketoreduction.
      Experiments conducted in vitro with the truncated DEBS Module 6+TE (M6+TE) enzyme
      purified from Escherichia coli indicated that any of three mutations, Tyr -->
      Phe, Ser --> Ala, and Lys --> Glu, abolish KR activity in formation of the
      triketide lactone product from a diketide substrate. The same mutations were also
      introduced in module 6 of the full DEBS gene set and expressed in Streptomyces
      lividans for in vivo analysis. In this case, the Tyr --> Phe mutation appeared to
      completely eliminate KR6 activity, leading to the 3-keto derivative of 6
      deoxyerythronolide B, whereas the other two mutations, Ser --> Ala and Lys -->
      Glu, result in a mixture of both reduced and unreduced compounds at the C-3
      position. The results support a model analogous to SDRs in which the conserved
      tyrosine serves as a proton donating catalytic residue. In contrast to deletion
      of the entire KR6 domain of DEBS, which causes a loss in substrate specificity of
      the adjacent acyltransferase (AT) domain in module 6, these mutations do not
      affect the AT6 specificity and offer a potentially superior approach to KR
      inactivation for engineered biosynthesis of novel polyketides. The homology
      modeling studies also led to identification of amino acid residues predictive of
      the stereochemical nature of KR domains. Finally, a method is described for the
      rapid purification of engineered PKS modules that consists of a biotin
      recognition sequence C-terminal to the thioesterase domain and adsorption of the
      biotinylated module from crude extracts to immobilized streptavidin. Immobilized
      M6+TE obtained by this method was over 95% pure and as catalytically effective as
      M6+TE in solution.

PMID- 12515541
TI  - Solution structure and functional ligand screening of HI0719, a highly conserved
      protein from bacteria to humans in the YjgF/YER057c/UK114 family.
AB  - HI0719 belongs to a large family of highly conserved proteins with no definitive
      molecular function and is found in organisms ranging from bacteria to humans. We
      describe the NMR structure of HI0719, the first solution structure for a member
      of this family. The overall fold is similar to the crystal structures of two
      homologues, YabJ from Bacillus subtilis and YjgF from Escherichia coli, and all
      three structures are similar to that of chorismate mutase, although there is
      little sequence homology and no apparent functional connection. HI0719 is a
      homotrimer with a distinct cavity located at the subunit interface. Six of the
      seven invariant residues in the high identity group of proteins are located in
      this cavity, suggesting that this may be a binding site for small molecules.
      Using previously published observations about the biological role of HI0719
      family members as a guide, over 100 naturally occurring small molecules or
      structural analogues were screened for ligand binding using NMR spectroscopy. The
      targeted screening approach identified six compounds that bind to HI0719 at the
      putative active site. Five of these compounds are either alpha-keto acids or
      alpha,beta-unsaturated acids, while the sixth compound is structurally similar.
      Previous studies have proposed that some HI0719 homologues may act on small
      molecules in the isoleucine biosynthetic path and, if this is correct, the ligand
      screening results presented here suggest that the interaction most likely occurs
      with 2-ketobutyrate and/or its unstable enamine precursor.

PMID- 12515542
TI  - Dictyostelium myosin II mutations that uncouple the converter swing and ATP
      hydrolysis cycle.
AB  - During the ATP hydrolysis cycle of the Dictyostelium myosin II motor domain, two
      conserved alpha-helices, the SH1/SH2 helix and the relay helix, rotate in a
      coordinated way to induce the swing motion of the converter domain. A network of
      hydrophobic and ionic interactions in these two helices and the converter may
      ensure that the motions of these helices are effectively transmitted to the
      converter. To examine the roles of these interactions in the ATPase-dependent
      converter swing, we disrupted two conserved hydrophobic linkages among them by
      means of a point mutation (I499A or F692A). The resulting mutations induced only
      limited changes in the kinetic parameters of ATP hydrolysis, except for a marked
      increase of basal MgATPase activity. However, the mutant myosins completely lost
      their in vitro and in vivo motor functions. Measurements of the intrinsic
      tryptophan fluorescence and the GFP-based FRET revealed that the converter domain
      of these mutants did not swing during steady-state ATP hydrolysis or in the
      presence of tightly trapped Mg.ADP.V(i), which shows that the point mutations
      induced the uncoupling of the converter swing and ATP hydrolysis cycle. These
      results highlight the importance of these hydrophobic linkages for transmitting
      the coordinated twist motions of the helices to the converter as well as the
      requirement of this converter swing for force generation.

PMID- 12515543
TI  - Membrane-bound orientation and position of the synaptotagmin I C2A domain by site
      directed spin labeling.
AB  - Site-directed spin labeling was used to determine the membrane orientation and
      insertion of the C2A domain from synaptotagmin I. A series of single cysteine
      mutants of the C2A domain of synaptotagmin I was prepared and labeled with a
      sulfhydryl specific spin label. Upon Ca2+ or membrane binding, the EPR line
      shapes of these mutants reveal dramatic decreases in label mobility within the
      Ca2+-binding loops. This loss in mobility is likely due in part to a reduction in
      local backbone fluctuations within the loop regions. Power saturation was then
      used to determine the position of each spin-labeled site along the bilayer
      normal, and these EPR distance constraints were used along with the high
      resolution solution structure of C2A to generate a model for the orientation and
      position of the domain at the membrane interface. This model places the
      polypeptide backbone of both the first and third Ca2+-binding loops in contact
      with the membrane interface, with several labeled side chains lying within the
      bilayer interior. All three Ca2+-binding sites lie near a plane defined by the
      lipid phosphates. This model indicates that there is some desolvation of this
      domain upon binding and that hydrophobic as well as electrostatic interactions
      contribute to the binding of C2A. When compared to the C2 domain from cPLA2
      (Frazier et al. (2002) Biochemistry 41, 6282), a similar orientation for the beta
      sandwich region is found; however, the cPLA2 C2 domain is translocated 5-7 A
      deeper into the membrane hydrocarbon. This difference in depth is consistent with
      previous biophysical data and with the difference that long-range electrostatic
      interactions and desolvation are expected to make to the binding of these two C2
      domains.

PMID- 12515544
TI  - Characterization of the S272A,D site-directed mutations of O-acetylserine
      sulfhydrylase: involvement of the pyridine ring in the alpha,beta-elimination
      reaction.
AB  - O-Acetylserine sulfhydrylase catalyzes the synthesis of l-cysteine from O-acetyl
      l-serine (OAS) and inorganic bisulfide. An anti-E2 mechanism has been proposed
      for the OASS-catalyzed elimination of acetate from OAS (Tai, C.-H., and Cook, P.
      F. (2001) Acc. Chem. Res. 34, 49-59). Site-directed mutagenesis was used to
      change S272 to alanine, which would be expected to eliminate the hydrogen bond to
      N1 of PLP or to aspartate, which would be expected to enhance the hydrogen
      bonding interaction. Both mutant enzymes catalyze the overall reaction and are in
      fact still good enzymes, consistent with the proposed anti-E2 mechanism. Data
      suggest that hydrogen bonding to the pyridine ring does not play a significant
      role in the alpha,beta-elimination reaction catalyzed by OASS-A. The V/K(OAS),
      which reflects the first half-reaction, is identical to the wild-type enzyme in
      the case of the S272D mutant enzyme and is decreased by only a factor of 3 in the
      case of the S272A mutant enzyme. In the case of the alanine mutation, and to a
      lesser extent the aspartate mutation, a decrease in the rate of the elimination
      is compensated by an increase in affinity for OAS, leading to the observed second
      order rate constant, V/K. The decrease in the rate of the elimination is proposed
      to result from a change in the orientation of the bound cofactor, as might be
      expected since one of the ligands that determines the position of the bound PLP
      has been changed. Consistent with a change in the orientation of the cofactor are
      the results from a number of the spectral probes. The visible CD data for the
      internal Schiff base have a molar ellipticity 50% that of wild-type enzyme, and
      the alpha-aminoacrylate intermediate has a molar ellipticity 25% that of wild
      type enzyme. The alpha-aminoacrylate intermediate can be formed from l-cysteine
      and l-serine with the S272A,D mutant enzymes, but not with the wild-type enzyme,
      and taken together with the increased K(d) for the serine external Schiff base is
      consistent with a change in cofactor orientation in the active site. The long
      wavelength fluorescence emission for the S272A mutant enzyme, attributed to
      Forster resonance energy transfer (McClure, G. D., Jr., and Cook, P. F. (1994)
      Biochemistry 33, 1647-1683) has an intensity near zero, as compared to
      significant fluorescence for the wild-type enzyme.

PMID- 12515545
TI  - Functional roles of streptokinase C-terminal flexible peptide in active site
      formation and substrate recognition in plasminogen activation.
AB  - The bacterial protein streptokinase (SK) activates human plasminogen (Pg) into
      the fibrinolytic protease plasmin (Pm). Roughly 40 residues from the SK C
      terminal domain are mobile in the crystal structure of SK complexed with the
      catalytic domain of Pm, and the functions of this C-tail remain elusive. To
      better define its roles in Pg activation, we constructed and characterized three
      C-terminal truncation mutants containing SK residues 1-378, 1-386, and 1-401,
      respectively. They exhibit gradually reduced amidolytic activity and Pg-activator
      activity, as well as marginally decreased binding affinity toward Pg, as more of
      the C-terminus is deleted. As compared with full-length SK, the shortest
      construct, SK(1-378), exhibits an 80% decrease in amidolytic activity
      (k(cat)/K(M)), an 80% decrease in Pg-activator activity, and a 30% increase in
      the dissociation constant toward the Pg catalytic domain. The C-terminal
      truncation mutations did not attenuate the resistance of the SK-Pm complex to
      alpha(2)-antiplasmin. Attempts at using a purified C-tail peptide to rescue the
      activity loss of the truncation mutants failed, suggesting that the integrity of
      the SK C-terminal peptide is important for the full function of SK.

PMID- 12515546
TI  - Identification and characterization of an angiogenin-binding DNA sequence that
      stimulates luciferase reporter gene expression.
AB  - Angiogenin undergoes nuclear translocation in endothelial and smooth muscle cells
      where it accumulates in the nucleolus and binds to DNA. Nuclear translocation of
      angiogenin is necessary for its biological activity and is mediated by an
      endocytotic pathway that is independent of the microtubule system and lysosomal
      processing. Because the nucleolus is a subnuclear organelle containing clusters
      of transcriptionally active ribosomal RNA genes, we studied the binding of
      angiogenin to the intergenic spacer of the ribosomal RNA gene where many of the
      transcription regulatory elements are located. Here we report that angiogenin
      binds to CT repeats that are abundant in the nontranscribed region of the
      ribosomal RNA gene. An angiogenin-binding DNA sequence (CTCTCTCTCTCTCTCTCCCTC)
      has been identified and designated angiogenin-binding element (ABE). ABE binds
      angiogenin specifically and exhibits angiogenin-dependent promoter activity in a
      luciferase reporter system. CT repeats, or inverted GA box, which are abundantly
      distributed in the eukaryotic genome and are often located in the 5'-flanking
      region, have been implicated in regulating gene expression. We have previously
      shown that angiogenin stimulates rRNA synthesis. The present results suggest that
      the nuclear function of angiogenin may not only be related to rRNA production but
      also play a role in regulating expression of genes containing CT repeats.

PMID- 12515547
TI  - Redox control of platelet aggregation.
AB  - Sulfhydryl and disulfide metabolism in platelet function has recently reemerged
      as a focus of platelet research. In this study we tested the effect of redox
      buffer on platelet aggregation and the effect of reduced glutathione (GSH) and
      platelet activation on sulfhydryl exposure in the platelet fibrinogen receptor,
      alpha IIb beta 3. In the presence of subthreshold concentrations of agonist,
      physiologic concentrations of GSH (10 microM) stimulated platelet aggregation and
      secretion. These effects were found with more than one platelet agonist and with
      different low molecular weight thiols, including homocysteine. The effect of low
      molecular weight thiols was reproduced with the peptide LSARLAF which directly
      activates platelets through alpha IIb beta 3, suggesting that the mechanism is at
      the level of this integrin. After determining optimal sulfhydryl labeling
      conditions for alpha IIb beta 3 (5 mM EDTA, 37 degrees C, 60 min), we found that
      GSH (10 microM) generated sulfhydryls in the beta 3 subunit. To determine if the
      requirement was for reducing equivalents or for a redox potential (ratio of GSH
      to GSSG), aggregation was further studied with the addition of low concentrations
      of GSSG to the GSH. With a ratio of GSH/GSSG of 5/1, similar to that of blood,
      the addition of GSSG potentiated the stimulatory effect as compared to GSH alone.
      This indicates that, for potentiation of aggregation, GSH is not simply reducing
      disulfide bonds; there is rather a requirement for a certain redox potential.
      Additional studies performed in the absence of added glutathione showed an
      increase in sulfhydryl labeling in the beta 3 subunit during platelet activation.
      Finally, we show that vicinal dithiols of platelet surface proteins are involved
      in the sulfhydryl-dependent pathways of platelet activation. In summary, these
      data imply that the redox potential of blood regulates activation of the alpha
      IIb beta 3 integrin and together with other reports in the literature suggest
      that disulfide bond cleavage with sulfhydryl generation in beta 3 is involved in
      activation of this receptor.

PMID- 12515548
TI  - Notch and the amyloid precursor protein are cleaved by similar gamma
      secretase(s).
AB  - Gamma-secretase is an intramembrane-cleaving protease whose substrates include
      Notch and the amyloid precursor protein (APP). On the basis of initial genetic
      and pharmacologic data, the gamma-secretase activity responsible for cleavage of
      both proteins appears to be identical. However, apparent differences in the
      cleavage site and in sequence specificity raise questions about the degree of
      similarity between Notch and APP gamma-like proteolysis. In an effort to resolve
      this issue directly, we established an in vitro gamma-secretase activity assay
      that cleaves both APP- and Notch-based substrates, C100Flag and N100Flag.
      Analysis with specific gamma-secretase inhibitors, dominant-negative gamma
      secretase preparations, and antibody co-immunoprecipitations all demonstrated
      identical cleavage of these substrates. Most importantly, we found that these
      substrates prevented cleavage of each other, indicating that the same gamma
      secretase complex can cleave either protein. Finally, we provide evidence that
      both substrates are cut at two distinct regions in the transmembrane domain.
      These data resolve some of the apparent conflicts and strongly indicate that
      Notch and APP are proteolyzed by the same enzyme(s).

PMID- 12515549
TI  - Mn2+ binding to factor VIII subunits and its effect on cofactor activity.
AB  - Metal ions, such as Ca2+ and Mn2+, are necessary for the generation of cofactor
      activity following reconstitution of factor VIII from its isolated light chain
      (LC) and heavy chain (HC). Titration of EDTA-treated factor VIII with Mn2+ showed
      saturable binding with high affinity (K(d) = 5.7 +/- 2.1 microM) as detected
      using a factor Xa generation assay. No significant competition between Ca2+ and
      Mn2+ for factor VIII binding (K(i) = 4.6 mM) was observed as measured by
      equilibrium dialysis using 20 microM Ca2+ and 8 microM factor VIII in the
      presence of 0-1 mM Mn2+. The intersubunit affinity measured by fluorescence
      energy transfer of an acrylodan-labeled LC (fluorescence donor) and fluorescein
      labeled HC (fluorescence acceptor) in the presence of 20 mM Mn2+ (K(d) = 53.0 +/-
      17.1 nM) was not significantly different from the affinity value previously
      obtained in the absence of metal ion (K(d) = 53.8 +/- 14.2 nM). The sensitization
      of phosphorescence of Tb3+ bound to factor VIII subunits was utilized to detect
      Mn2+ binding to the subunits. Mn2+ inhibited the phosphorescence of Tb3+ bound to
      HC and LC, as well as the HC-derived A1 and A2 subunits with a relatively wide
      range of estimated inhibition constant values (K(i) values = 169-1147 microM),
      whereas Ca2+ showed no effect on Tb3+ phosphorescence. These results suggest that
      factor VIII cofactor activity can be generated by Mn2+ binding to site(s) on
      factor VIII that are different from the high-affinity Ca2+ binding site. However,
      like Ca2+, Mn2+ did not alter the affinity for HC and LC association. Thus,
      Mn2+appears to generate factor VIII cofactor activity by a similar mechanism as
      observed for Ca2+following its association at nonidentical sites on the protein.

PMID- 12515550
TI  - Computational and in vitro analysis of destabilized DNA regions in the interferon
      gene cluster: potential of predicting functional gene domains.
AB  - Recent evidence adds support to a traditional concept according to which the
      eukaryotic nucleus is organized into functional domains by scaffold or matrix
      attachment regions (S/MARs). These regions have previously been predicted to have
      a high potential for stress-induced duplex destabilization (SIDD). Here we report
      the parallel results of binding (reassociation) and computational SIDD analyses
      for regions within the human interferon gene cluster on the short arm of
      chromosome 9 (9p22). To verify and further refine the biomathematical methods, we
      focus on a 10 kb region in the cluster with the pseudogene IFNWP18 and the
      interferon alpha genes IFNA10 and IFNA7. In a series of S/MAR binding assays, we
      investigate the promoter and termination regions and additional attachment
      sequences that were detected in the SIDD profile. The promoters of the IFNA10 and
      the IFNA7 genes have a moderate approximately 20% binding affinity to the nuclear
      matrix; the termination sequences show stronger association (70-80%) under our
      standardized conditions. No comparable destabilized elements were detected
      flanking the IFNWP18 pseudogene, suggesting that selective pressure acts on the
      physicochemical properties detected here. In extended, noncoding regions a
      striking periodicity is found of rather restricted SIDD minima with scaffold
      binding potential. By various criteria, the underlying sequences represent a new
      class of S/MARs, thought to be involved in a higher level organization of the
      genome. Together, these data emphasize the relevance of SIDD calculations as a
      valid approach for the localization of structural, regulatory, and coding regions
      in the eukaryotic genome.

PMID- 12515551
TI  - Amino acid residues of Escherichia coli acyl carrier protein involved in
      heterologous protein interactions.
AB  - Acyl carrier protein (ACP) is a small, highly conserved protein with an essential
      role in a myriad of reactions throughout lipid metabolism in plants and bacteria
      where it interacts with a remarkable diversity of proteins. The nature of the
      proper recognition and precise alignment between the protein moieties of ACP and
      its many interactive proteins is not understood. Residues conserved among ACPs
      from numerous plants and bacteria were considered as possibly being crucial to
      ACP's function, including protein-protein interaction, and a method of
      identifying amino acid residue clusters of high hydrophobicity on ACP's surface
      was used to estimate residues possibly involved in specific ACP-protein
      interactions. On the basis of this information, single-site mutation analysis of
      multiple residues, one at a time, of ACP was used to probe the identities of
      potential contact residues of ACPSH or acyl-ACP involved in specific interactions
      with selected enzymes. The roles of particular ACP residues were more precisely
      defined by site-directed fluorescence analyses of various myristoyl-mutant-ACPs
      upon specific interaction with the Escherichia coli hemolysin-activating
      acyltransferase, HlyC. This was done by selectively labeling each mutated site,
      one at a time, with an environmentally sensitive fluoroprobe and observing its
      fluorescence behavior in the absence and presence of HlyC. Consequently, a
      picture of the portion of ACP involved in selected macromolecular interaction has
      emerged.

PMID- 12515552
TI  - Polarized absorption spectra of green fluorescent protein single crystals:
      transition dipole moment directions.
AB  - Polarized absorption spectra of orthorhombic crystals of wild-type green
      fluorescent protein (GFP) were measured between 350 and 520 nm to obtain
      information on the directions of the electronic transition dipole moments ((-
      >)m) of the chromophore relative to the molecular axes. The transition dipole
      moment orientation is a basic spectroscopic parameter of relevance to biologists
      when interpreting Forster-type fluorescence resonance energy transfer data and
      for comparing absorbance and fluorescence spectra of GFP with quantum chemical
      calculations. Maximal extinction was obtained throughout the spectrum when the
      polarization direction of the electric vector of incident light was parallel to
      the c-axis of the crystal. The transition dipole moments were assumed to be
      parallel to the plane of the chromophore. With this assumption and the measured
      dichroic ratios in the crystals, the transition dipole moments associated with
      the neutral (lambda(max) = 398 nm) and anionic (lambda(max) = 478 nm) forms of
      the chromophore were found to subtend angles of approximately 26 degrees and 13
      degrees (counterclockwise), respectively, with the vector that joins the phenolic
      and imidazolinone oxygen atoms of the chromophore.

PMID- 12515553
TI  - Remarkable stabilization of neutrophil NADPH oxidase using RacQ61L and a p67phox
      p47phox fusion protein.
AB  - Activation of the phagocyte NADPH oxidase occurs via assembly of cytosolic
      p47(phox), p67(phox), and Rac with the membrane-bound flavocytochrome b(558).
      Recently, we have found that p67(phox)-(1-210) (p67N) fused with p47(phox)-(1
      286) (p47N) or with Rac efficiently stabilizes the oxidase in a cell-free
      reconstitution system. In an attempt to further stabilize the oxidase, we herein
      used a constitutively active Rac, RacQ61L, and examined its effect on the oxidase
      stability. The half-life (t(1/2)) of the activity reconstituted with wild-type
      Rac was 12 min at 37 degrees C, which was extended 6-fold by RacQ61L. Also, the
      stability of the oxidase without p47(phox) increased 8-fold using RacQ61L.
      RacQ61L had a higher affinity for the complex than wild-type Rac and increased
      the affinity of p67N for the complex. Far-western blotting showed an enhanced
      binding between RacQ61L and p67N. The oxidase was stabilized by nanomolar FAD,
      and RacQ61L lowered the FAD concentration required. The combination of RacQ61L
      and a fusion protein consisting of p67N and p47N produced an extremely stable
      enzyme (t(1/2) = 184 min at 37 degrees C). The effectiveness of RacQ61L and
      fusion proteins on stabilization was in the following order: p67N-Rac < p67N +
      RacQ61L < or = p67N-RacQ61L << p67N-p47N + RacQ61L. These results indicate that a
      tightly bound ternary complex of p67(phox), Rac, and p47(phox) is very effective
      in maintaining the oxidase and confirm that the longevity of the activated state
      requires continuous association of these components. This simple and efficient
      method of stabilization may provide a useful tool to elucidate the nature of the
      activated oxidase.

PMID- 12515554
TI  - Mycobacterium tuberculosis ketopantoate hydroxymethyltransferase:
      tetrahydrofolate-independent hydroxymethyltransferase and enolization reactions
      with alpha-keto acids.
AB  - The panB gene that encodes ketopantoate hydroxymethyltransferase has been cloned
      from Mycobacterium tuberculosis, expressed, and purified to homogeneity. 1H NMR
      spectroscopy was used to determine the rate of (i) tetrahydrofolate-independent
      hydroxymethyltransferase chemistry between formaldehyde and alpha-ketoisovalerate
      and (ii) deuterium exchange in the methylenetetrahydrofolate-independent
      enolization of alpha-ketoisovalerate and other alpha-keto acids, catalyzed by
      PanB. These studies have demonstrated that substrate enolization by PanB is
      divalent metal-dependent with a preference of Mg2+ > Zn2+ > Co2+ > Ni2+ > Ca2+.
      The rate of enolization is pH-dependent with optimal activity in the range of 7.0
      7.5. The pH profile was bell-shaped, depending on the ionization state of two
      ionizable groups with apparent pK values of 6.2 and 8.3. Enolization and isotope
      exchange occurs with some alpha-keto acids (e.g., pyruvate and alpha
      ketobutyrate), resulting in the complete exchange of all beta-hydrogens. Enzyme
      catalyzed enolization and isotope exchange occur with other long-chain and
      branched alpha-keto acids, resulting in the stereospecific exchange of only one
      of the beta-hydrogen atoms. These results are discussed in the context of steric
      restrictions present in the enzyme active site and the stereochemistry of base
      catalyzed isotope exchange.

PMID- 12515555
TI  - Quantitative analysis of loading and extender acyltransferases of modular
      polyketide synthases.
AB  - The acyltransferase (AT) domains of modular polyketide synthases (PKSs) are the
      primary determinants of building block specificity in polyketide biosynthesis and
      are therefore attractive targets for protein engineering. Thus far,
      investigations into the fundamental biochemical properties of AT domains have
      been hampered by the inability to produce these enzymes as self-standing
      polypeptides. Here we describe an alternative, generally applicable strategy for
      overexpression and analysis of AT domains from modular PKSs as truncated didomain
      proteins (approximately 60 kDa). Recently, we reported the expression and
      reconstitution of the loading didomain of 6-deoxyerythronolide B synthase (Lau,
      J., Cane, D. E., and Khosla, C. (2000) Biochemistry 39, 10514-20). By replacing
      the AT domain of this protein with a methylmalonyl-CoA specific AT domain from
      module 6 of the 6-deoxyerythronolide B synthase, or alternatively a malonyl-CoA
      specific AT domain from module 2 of the rapamycin synthase, each of these
      extender unit AT domains could be overproduced and purified to homogeneity. Using
      acyl-CoA substrates as acyl group donors and N-acetylcysteamine as the thiol
      acceptor, we devised a steady-state kinetic assay to probe the properties of
      these three didomain proteins and selected mutants. Propionyl-CoA was the
      preferred substrate of the loading didomain, although acetyl- and butyryl-CoA
      were also accepted with approximately 40-fold-lower specificity. In contrast to
      the relatively relaxed specificity of the loading AT domain, the methylmalonyl-
      and malonyl-specific AT domains had high specificity (>1000-fold) toward their
      natural substrates. The acyl transfer reaction was inhibited by coenzyme A
      (CoASH) with both a competitive and a noncompetitive component. Use of an
      exogenous holo-acyl carrier protein (ACP) as an acceptor thiol did not increase
      the rate of acyl transfer relative to the reaction involving N-acetylcysteamine,
      suggesting that either the on-rate of the acyl group is rate-limiting or that the
      apo-ACP component of the didomain protein precludes effective docking of a second
      ACP onto the AT active site. Mutation of Trp-222 in the loading AT domain to an
      Arg residue that is universally conserved in all extender unit AT domains failed
      to enable the loading AT domain to accept methylmalonyl-CoA as an alternative
      substrate. In contrast, mutation of the equivalent Arg residue in an extender AT
      domain resulted in a protein with no activity. Together, these results provide a
      foundation for future structural and mechanistic investigations into the
      properties of AT domains of modular PKSs.

PMID- 12515556
TI  - Differential ligand recognition by the Src and phosphatidylinositol 3-kinase Src
      homology 3 domains: circular dichroism and ultraviolet resonance Raman studies.
AB  - Src homology 3 (SH3) domains recognize Pro-rich motifs using a hydrophobic cleft
      which contains several conserved aromatic residues. To investigate how aromatic
      residues contribute to ligand recognition, circular dichroism (CD) and 235 nm
      excited ultraviolet resonance Raman spectroscopies have been applied to Src and
      phosphatidylinositol 3-kinase (PI3K) SH3s. The CD analysis shows that Src SH3
      binds to RPLPPLP (R-core) using aromatic residues with a dissociation constant
      (K(d)) of 10 microM. Moreover, intensity increases of the Trp and Tyr Raman bands
      suggest that the interaction is mediated by hydrophobic contacts and/or hydrogen
      bond formation with both Trp and Tyr residues. In the interaction of Src SH3 with
      VSLARRPLPPLP (VSL12) (K(d) 0.8 microM), Trp118 appears to form a strong hydrogen
      bond with VSL12, judging from significant intensity increases of the Trp Raman
      bands and the reported complex structure. In contrast, PI3K SH3 binds to R-core
      and VSL12 with lower affinities (K(d) 34 and 18 microM, respectively), and the
      interactions are suggested to be mediated mainly by hydrophobic contacts and/or
      hydrogen bond formation with Tyr residue(s). In the D21N mutant (Asp21 --> Asn)
      of PI3K SH3, whose hydrophobic cleft is deformed, Trp55 is shown to be
      responsible for the interaction with VSL12 by intensity increases of the Trp
      Raman bands. However, the affinity is severely decreased (K(d) 330 microM). These
      observations imply that SH3 domains associate with their ligands with distinct
      use of aromatic residues and that hydrogen bond formation with an SH3-conserved
      Trp residue in the well-ordered hydrophobic cleft is important for stable complex
      formation.

PMID- 12515557
TI  - A Cys3His zinc-binding domain from Nup475/tristetraprolin: a novel fold with a
      disklike structure.
AB  - Nup475 (also known as tristetraprolin and TIS11) includes two zinc-binding
      domains of the form Cys-X8-Cys-X5-Cys-X3-His. These domains are required for
      rapid degradation of tumor necrosis factor (TNF) and other mRNAs through the
      interaction with AU-rich elements in their 3'-untranslated regions. The three
      dimensional solution structure of the first domain was determined by
      multidimensional nuclear magnetic resonance spectroscopy, revealing a novel fold
      around a central zinc ion. The core structure is disk-like with a diameter of
      approximately 25 A and a width of approximately 12 A. This structure provides a
      basis for evaluating the role of individual residues for structural stability and
      for nucleic acid binding.

PMID- 12515558
TI  - A novel binuclear [CuSMo] cluster at the active site of carbon monoxide
      dehydrogenase: characterization by X-ray absorption spectroscopy.
AB  - The structurally characterized molybdoenzyme carbon monoxide dehydrogenase (CODH)
      catalyzes the oxidation of CO to CO2 in the aerobic bacterium Oligotropha
      carboxidovorans. The active site of the enzyme was studied by Mo- and Cu-K-edge X
      ray absorption spectroscopy. This revealed a bimetallic [Cu(I)SMo(VI)(double bond
      O)2] cluster in oxidized CODH which was converted into a [Cu(I)SMo(IV)(double
      bond O)OH2] cluster upon reduction. The Cu...Mo distance is 3.70 A in the
      oxidized form and is increased to 4.23 A upon reduction. The bacteria contain
      CODH species with the complete and functional bimetallic cluster along with
      enzyme species deficient in Cu and/or bridging S. The latter are precursors in
      the posttranslational biosynthesis of the metal cluster. Cu-deficient CODH is the
      most prominent precursor and contains a [HSMo(double bond O)OH2] cluster. Se-K
      edge X-ray absorption spectroscopy demonstrates that Se is coordinated by two C
      atoms at 1.94-1.95 A distance. This is interpreted as a replacement of the S in
      methionine residues. In contrast to a previous report [Dobbek, H., Gremer, L.,
      Meyer, O., and Huber, R. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 8884-8889] Se
      was not identified in the active site of CODH.

PMID- 12515559
TI  - Phospholipid flop induced by transmembrane peptides in model membranes is
      modulated by lipid composition.
AB  - Since phospholipid synthesis is generally confined to one leaflet of a membrane,
      membrane growth requires phospholipid translocation (flip-flop). It is generally
      assumed that this process is protein-mediated; however, the mechanism of flip
      flop remains elusive. Previously, we have demonstrated flop of 2-[6-[(7-nitro
      2,1,3-benzoxadiazol-4-yl)amino]caproyl] (C6NBD) phospholipids, induced by the
      presence of membrane-spanning peptides in vesicles composed of an Escherichia
      coli phospholipid extract, supporting the hypothesis that the presence of
      transmembrane stretches of proteins in the bilayer is sufficient to allow
      phospholipid flip-flop in the inner membrane of E. coli [Kol et al. (2001)
      Biochemistry 40, 10500]. Here, we investigated whether the specific phospholipid
      composition of E. coli is a prerequisite for transmembrane helix-induced flop of
      phospholipids. This was tested by determining the amount of C6NBD-phospholipid
      that was translocated from the inner leaflet to the outer leaflet of a model
      membrane in time, using a dithionite reduction assay. The transmembrane peptides
      GWWL(AL)8WWA (WALP23) and GKKL(AL)8KKA (KALP23) induced phospholipid flop in
      model membranes composed of various lipid mixtures. The rate of peptide-induced
      flop was found to decrease with increasing dioleoylphosphatidylethanolamine
      (DOPE) content of vesicles composed of DOPE and dioleoylphosphatidylcholine
      (DOPC), and the rate of KALP23-induced flop was shown to be stimulated by higher
      dioleoylphosphatidylglycerol (DOPG) content in model membranes composed of DOPG
      and DOPC. Furthermore, the incorporation of cholesterol had an inhibitory effect
      on peptide-induced flop. Finally, flop efficiency was strongly dependent on the
      phospholipid headgroup of the NBD-phospholipid analogue. Possible implications
      for transmembrane helix-induced flop in biomembranes in general are discussed.

PMID- 12515561
TI  - Ischaemic preconditioning and outcomes after angioplasty: effects of drug
      therapy.
AB  - Ischaemic preconditioning is one of the mechanisms by which human myocardium and
      human life are protected from ischaemic insults. One of the clinical situations
      in which we can discuss preconditioning is repetitive coronary occlusions by
      balloon inflation during elective percutaneous transluminal coronary angioplasty
      (PTCA) for stable angina pectoris. The severity of myocardial ischaemia assessed
      by ST-segment elevation or chest pain is less during the second balloon inflation
      compared with the first, if the duration of the first coronary occlusion is
      sufficient to precondition the myocardium. Many drugs have been identified that
      produce a reduction or induction in indices of preconditioning during PTCA.
      Preconditioning-mimetic drugs include adenosine, bradykinin, nitroglycerin and
      nicorandil. It is of paramount importance that we investigate and develop
      preconditioning-mimetic drugs which may enable an increased tolerance to effort
      angina, limit infarction size in susceptible patients, and decrease the incidence
      of sudden cardiac death as a result of ventricular tachyarrhythmias.

PMID- 12515562
TI  - The pleiotropic effects of HMG-CoA reductase inhibitors: their role in
      osteoporosis and dementia.
AB  - HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and its
      inhibition exerts profound effects on cellular metabolism. Inhibitors of this
      enzyme are used in clinical practice to lower plasma cholesterol levels and are
      commonly collectively referred to as 'statins'. A number of in vitro, in vivo
      animal, and clinical studies suggest that properties of statins other than
      cholesterol lowering may be of biological importance. These diverse properties
      are often referred to as 'pleiotropic' and suggest that statins may affect a
      number of diseases of ageing. In this article we review the biological
      plausibility and clinical evidence of a role for statins in modulating two
      diseases of ageing: osteoporosis and dementia (including Alzheimer's disease). In
      both diseases, there is a sound cellular and laboratory basis for a plausible
      therapeutic effect of statins. In the case of osteoporosis, there are conflicting
      data regarding clinical benefit, with both negative and positive results
      reported. In particular, secondary analyses of randomised, controlled studies
      have shown no reduction of fracture risk by statins. In the case of dementia
      there are fewer clinical studies but there is clear anticipated benefit in
      macrovascular dementias attributable to statin-mediated reduction of the risk of
      stroke. Overall, there are a lack of prospective, placebo-controlled, randomised
      data testing statins and modulation of the risk of osteoporosis-related fracture
      or of clinical dementia, where these are primary outcomes. Until such data are
      available, the use of statins appears promising but cannot be recommended as a
      primary therapeutic modality for either condition.

PMID- 12515563
TI  - Bladder, bowel and sexual dysfunction in multiple sclerosis: management
      strategies.
AB  - Although patients with multiple sclerosis (MS) are likely to have problems with
      bladder, bowel and sexual function, these problems have often been neglected in
      the past. Bladder dysfunction produces symptoms of urgency, frequency and urge
      incontinence (due to bladder overactivity and incomplete emptying), and is found
      in up to 75% of patients with MS. The mainstay of drug treatment for neurogenic
      bladder overactivity is anticholinergic medication, although intravesical
      treatments have also been proposed, such as the vanilloids and botulinum toxin,
      as well as sublingual cannibanoids. There has been much progress with pro
      erectile agents in recent years, notably the use of sildenafil citrate, which has
      been shown to be particularly efficacious in these patients. Other agents include
      apomorphine hydrochloride and newer phosphodiesterase 5 inhibitors; however, the
      efficacy of these drugs in patients with MS remains to be proven. Research in
      female sexual dysfunction is also progressing, although this aspect of patient
      well being has only recently been addressed; the reported development of a
      classification system for the condition is likely to help categorise future
      treatments. Unlike bladder and sexual dysfunction, there have been rather limited
      advances in the treatment of faecal incontinence and constipation specifically
      for patients with MS, despite a prevalence of up to 50%. This review highlights
      the strategies for these types dysfunction commonly seen in patients with MS,
      with report of recent pharmacological developments.

PMID- 12515564
TI  - Newer drugs for the treatment of lupus nephritis.
AB  - This article first reviews the current treatment of lupus nephritis, with a focus
      on the most serious forms, that is, the proliferative subtypes. Current standards
      for treatment have been developed empirically. Corticosteroids form the basis of
      all regimens. Cyclophosphamide given intravenously for prolonged periods is the
      current gold standard. Azathioprine can be regarded as an effective drug for
      maintenance treatment of lupus nephritis. Studies on its efficacy in schedules
      for remission induction are in progress. It has been learned from studies on
      'conventional' immunosuppression that randomised, clinical trials should comprise
      large numbers of patients and a follow-up of many years to elucidate differences
      between effective strategies. These requirements are not met by any of the 'new'
      treatments we discuss in this review. There is only limited experience in
      patients with lupus nephritis with drugs that are currently used for
      immunosuppression in other autoimmune diseases, such as methotrexate, cyclosporin
      and high-dose intravenous gammaglobulins, nor with new immunosuppressive drugs
      that have been developed for immunosuppression in organ transplantation
      (mycophenolate mofetil, tacrolimus, fludarabine and cladribine). Hormonal therapy
      with the weak androgen prasterone (dehydroepiandrosterone; DHEA) has no role in
      treatment of active lupus nephritis. There are interesting experiences with
      agents that have evolved from progress in immunobiology and in our understanding
      of immunological processes. These modalities enable more specific
      immunosuppression and include monoclonal antibodies directed at immune cells,
      cytokines and components of the complement system, constructs developed to induce
      tolerance in pathogenic B cells, and gene therapy. Finally, we review data on
      autologous bone marrow transplantation in patients with systemic lupus
      erythematosus. We conclude that some strategies (like mycophenolate mofetil) are
      good candidates for further investigation in large-scale, prospective, randomised
      trials with prolonged follow-up (which are almost by definition hard to perform).
      Most new biological agents still are in a pre-clinical phase.

PMID- 12515565
TI  - International guidelines for the treatment of community-acquired pneumonia in
      adults: the role of macrolides.
AB  - The significance of community-acquired pneumonia (CAP) has led to the publication
      of guidelines from numerous international organisations. Because the macrolide
      class of antimicrobials is active against most of the key pathogens associated
      with CAP, agents from this class are commonly included in recommendations from
      these guidelines. However, there are differences among the various guidelines
      concerning the positioning of the macrolides for empirical therapy. An important
      factor concerning the use of macrolides for CAP is the emergence of resistance of
      Streptococcus pneumoniae over the past decade. The rate of S. pneumoniae
      resistance to macrolides ranges from 4 to 70% of strains in worldwide
      surveillance studies. The most common mechanisms of resistance include
      methylation of a ribosomal target encoded by the erm gene and efflux of the
      macrolides by a cell membrane protein transporter, encoded by the mef gene. S.
      pneumoniae strains with the mef gene are resistant at a lower level (with minimum
      inhibitory concentration [MIC] values generally 1-16 microg/ml) than erm
      resistant strains; and it is possible that such strains may be inhibited if
      sufficiently high levels of macrolide can be obtained at the infected site.
      Currently mef-associated resistance predominates in North America, whereas erm
      predominates in Europe. Until recently, reports of failure of treatment of CAP
      with macrolides has been rare, particularly for patients with low-risk for drug
      resistant strains. However, since 2000, several patients treated with an oral
      macrolide who have subsequently required admission to the hospital for macrolide
      resistant S. pneumoniae (MRSP) bacteraemia have been reported in the literature.
      Major issues, which are fundamental to the use of the macrolides as recommended
      in the various guidelines, include the importance of providing therapy for
      'atypical' pathogens and the clinical significance of MRSP. Presently, the
      macrolides are more prominently recommended in the North American guidelines than
      in other parts of the world. The difference in the emphasis placed on the
      importance of the atypical pathogens as well as the expression of MRSP in North
      America compared with Europe partly explains this variance.

PMID- 12515566
TI  - Combined two-dose hepatitis A and B vaccine (AmBirix).
AB  - One month after the last dose (i.e. at month 7), geometric mean titres (GMTs) of
      antibodies directed against hepatitis A virus (anti-HAV) were generally greater
      in participants (aged 12-15 years) receiving combined two-dose (0 and 6 months)
      hepatitis A and B vaccine (AmBirix) compared with the three-dose (containing one
      half the dose of the two active components per dose, given at 0, 1 and 6 months;
      Twinrix Paediatric) schedule. Moreover, at month 7 all patients had seroconverted
      to anti-HAV. GMTs of antibodies directed against hepatitis B surface antigen
      greatly exceeded the threshold for seroprotection (>/=10 mIU/mL) 1 month after
      the last dose of vaccine. Seroprotection rates against hepatitis B virus (HBV)
      were similar 1 month after completion of either a two- (97.9%) or three-dose
      (100%) vaccination schedule. At 24 months' follow-up, all patients tested
      remained positive for anti-HAV, and 93.3% and 96.2% of those treated with the two
      and three-dose schedules, respectively, remained above the threshold for
      seroprotection against HBV. Administering the second dose in the two-dose series
      at 12 months rather than at 6 months did not compromise the immune response to
      the combined vaccine in adolescents aged 12-15 years in a randomised, multicentre
      trial. Local adverse events reported in the 4 days following administration of
      combined two-dose hepatitis A and B vaccine include pain or soreness, redness and
      swelling; systemic symptoms included headache, fatigue, gastrointestinal events
      and fever.

PMID- 12515569
TI  - Capecitabine: a review of its pharmacology and therapeutic efficacy in the
      management of advanced breast cancer.
AB  - Capecitabine is an orally administered prodrug of fluorouracil which is indicated
      in the US and Europe, in combination with docetaxel, for the treatment of
      patients with metastatic breast cancer failing anthracycline therapy, and as
      monotherapy for metastatic breast cancer resistant to paclitaxel and
      anthracycline therapy (US) or failing intensive chemotherapy (Europe).
      Capecitabine is also approved for use in metastatic colorectal cancer.
      Capecitabine is metabolically activated preferentially at the tumour site, and
      shows antineoplastic activity and synergy with other cytotoxic agents including
      cyclophosphamide or docetaxel in animal models. Bioavailability after oral
      administration is close to 100%. In patients with pretreated advanced breast
      cancer, capecitabine is effective as monotherapy and also in combination with
      other agents. Combination therapy with capecitabine 1,250 mg/m(2) twice daily for
      2 weeks of every 3-week cycle plus intravenous docetaxel 75 mg/m(2) on day one of
      each cycle was superior to intravenous monotherapy with docetaxel 100 mg/m(2) on
      day one of each cycle. Capecitabine plus docetaxel significantly reduced the
      risks of disease progression and death by 35% (p = 0.0001) and 23% (p < 0.05),
      respectively, and significantly increased median survival (p < 0.05) and
      objective response rates (p < 0.01). Efficacy has also been demonstrated with
      capecitabine monotherapy and combination therapy in previously untreated patients
      in preliminary trials. The most common adverse effects occurring in patients
      receiving capecitabine monotherapy include lymphopenia, anaemia, diarrhoea, hand
      and-foot syndrome, nausea, fatigue, hyperbilirubinaemia, dermatitis and vomiting
      (all >25% incidence). While gastrointestinal events and hand-and-foot syndrome
      occurred more often with capecitabine than with paclitaxel or a regimen of
      cyclophosphamide, methotrexate and fluorouracil (CMF), neutropenic fever,
      arthralgia, pyrexia and myalgia were more common with paclitaxel, and nausea,
      stomatitis, alopecia and asthenia were more common with CMF. The incidence of
      adverse effects and hospitalisation was similar in patients receiving
      capecitabine plus docetaxel and those receiving docetaxel monotherapy. In
      conclusion, capecitabine, an oral prodrug of fluorouracil which is activated
      preferentially at the tumour site, is an effective and convenient addition to the
      intravenous polychemotherapeutic treatment of advanced breast cancer in
      pretreated patients, and also has potential as a component of first-line
      combination regimens. Combined capecitabine plus docetaxel therapy resulted in
      similar rates of treatment-related adverse effects and hospitalisation to those
      seen with docetaxel monotherapy. Capecitabine is also effective as monotherapy in
      pretreated patients and phase II data for capecitabine as first-line monotherapy
      are also promising. While gastrointestinal effects and hand-and-foot syndrome
      occur often with capecitabine, the tolerability profile was comparatively
      favourable for other adverse effects (notably, neutropenia and alopecia).

PMID- 12515570
TI  - Discounting in cost-utility analysis of healthcare interventions: reassessing
      current practice.
AB  - Cost-utility analysis (CUA) is a technique that can potentially be used as a
      guide to allocating healthcare resources so as to obtain the maximum health
      benefits possible under a given budget constraint. However, it is not clear that
      current practice captures societal preferences regarding health benefits. In
      analyses of healthcare interventions providing survival benefits, the market rate
      of interest is the sole empirical variable that reflects societal preferences.
      This approach is based on the assumptions that: (i) healthcare interventions
      should be ranked using cost-effectiveness (CE) ratios; (ii) the discount rate for
      costs in CUA should be equal to that used in cost-benefit analysis (CBA); (iii)
      the discount rate in CBA should be the market rate of interest on long-term
      government bonds; and (iv) the Keeler-Cretin paradox is applicable to CUA of
      healthcare interventions, so that the discount rate for benefits in CUA should be
      set equal to the discount rate for costs. This approach ignores a fundamental
      difference between CBA and CUA, namely that CUA assumes that a budget constraint
      has been specified prior to the analysis. It starts with the assumption that a
      given amount of funds have been withdrawn from the economy to fund healthcare, so
      there is no opportunity cost to consider. For that reason, the principles on
      which the choice of discount rate rests differ in the two techniques.
      Furthermore, use of CE ratios to rank interventions assumes that the budget
      constraint can be expressed as a single constraint. But healthcare budgets are
      multiyear budgets that are roughly constant from year to year. A more realistic
      model would involve multiple constraints and would require linear programming for
      solution. This can be reduced to a series of single constraints, thereby allowing
      use of the simpler CE ratio approach, if we assume that the budget being
      allocated is intended for one cohort at a time, i.e. all people for whom a new
      funding decision must be made in a given year. In general, we assume that future
      cohorts will be allotted comparable funding. However, the Keeler-Cretin paradox
      depends on the assumption that cohorts are competing with each other for
      resources, and is therefore not applicable to CUA of healthcare. Other approaches
      are therefore needed to assign utilities to healthcare interventions providing
      survival benefits. Methods should be developed that allow analyses to reflect a
      range of philosophical approaches through sensitivity analysis.

PMID- 12515571
TI  - European healthcare policies for controlling drug expenditure.
AB  - In the last 20 years, expenditures on pharmaceuticals - as well as total health
      expenditures - have grown faster than the gross national product in all European
      countries. The aim of this paper was to review policies that European governments
      apply to reduce or at least slow down public expenditure on pharmaceutical
      products. Such policies can target the industry, the wholesalers and retailers,
      prescribers, and patients. The objectives of pharmaceutical policies are
      multidimensional and must take into account issues relating to public health,
      public expenditure and industrial incentives. Both price levels and consumption
      patterns determine the level of total drug expenditure in a particular country,
      and both factors vary greatly across countries. Licensing and pricing policies
      intend to influence the supply side. Three types of pricing policies can be
      recognised: product price control, reference pricing and profit control. Profit
      control is mainly used in the UK. Reference pricing systems were first used in
      Germany and The Netherlands and are being considered in other countries. Product
      price control is still the most common method for establishing the price of
      drugs. For the aim of fiscal consolidation, price-freeze and price-cut measures
      have been frequently used in the 1980s and 1990s. They have affected all types of
      schemes. For drug wholesalers and retailers, most governments have defined profit
      margins. The differences in price levels as well as the introduction of a Single
      European Pharmaceutical Market has led to the phenomenon of parallel imports
      among member countries of the European Union. This may be facilitated by larger
      and more powerful wholesalers and the vertical integration between wholesalers
      and retailers. To control costs, the use of generic drugs is encouraged in most
      countries, but only few countries allow pharmacists to substitute generic drugs
      for proprietary brands. Various interventions are used to reduce the patients'
      demand for drugs by either denying or limiting reimbursement of products and
      providing an incentive for patients to reduce their consumption of drugs. These
      interventions include defining a list either of drugs reimbursed (positive list)
      or one of drugs not reimbursed (negative list), and patient co-payments, which
      require patients to pay a proportion of the cost of a prescribed product or a
      fixed charge. Policies intended to affect physicians' prescribing behaviour
      include guidelines, information (about price and less expensive alternatives) and
      feedback, and the use of budgetary restrictions.

PMID- 12515572
TI  - Cost of illness of atopic dermatitis in children: a societal perspective.
AB  - Childhood atopic dermatitis is a disorder with considerable social and financial
      costs. Consideration of these costs is increasingly important in view of the
      growing prevalence of atopic dermatitis, particularly in developed countries over
      recent decades. The family stress related to the care of children with moderate
      or severe atopic dermatitis is significantly greater than that of the care of
      children with type 1 diabetes mellitus. The factors contributing to family stress
      include sleep deprivation, loss of employment, time taken for care of atopic
      dermatitis and financial costs. The financial costs for the family and community
      include medical and hospital direct costs of treatments and indirect costs from
      loss of employment. There are many interventions utilised in the treatment of
      childhood atopic dermatitis which involve not only medical practitioners but
      nurses, pharmacists, dieticians, psychologists and purveyors of so-called
      alternative therapies such as naturopathy, aromatherapy and bioresonance, all of
      which contribute to the financial burdens on the parents and the community. It is
      possible that appropriate interventions directed to reducing trigger factors
      might produce worthwhile savings, although the cost benefit of these measures has
      not been demonstrated. In conclusion, atopic dermatitis should not be regarded as
      a minor skin disorder but as a condition which has the potential to be a major
      handicap with considerable personal, social and financial consequences both to
      the family and the community.

PMID- 12515573
TI  - Cost analysis of ropinirole versus levodopa in the treatment of Parkinson's
      disease.
AB  - BACKGROUND: Not all patients with Parkinson's disease (PD) respond to levodopa
      and others develop dyskinesias. Ropinirole, a dopamine agonist, is associated
      with fewer dyskinesias than levodopa. OBJECTIVE: To examine the economic impact
      of reducing dyskinesias using ropinirole instead of levodopa plus benserazide in
      PD was examined. The research question addressed was: is the added cost of
      ropinirole offset by savings due to avoided cases of dyskinesia? METHODS: A cost
      minimisation analysis was performed from both the societal and Ministry of Health
      (MoH) of Ontario, Canada perspectives, using 5-year data from a study of
      dyskinesia outcomes comparing ropinirole with levodopa plus benserazide. A
      predictive model was developed to capture resource utilisation over 5 years, such
      as medication costs, medical consultations, hospital admissions, nursing home
      admissions, caregiver time and productivity loss. The model was based on a
      previously reported clinical trial which determined dyskinesia rates to be 20%
      for ropinirole and 45% for levodopa. Standard costing lists were used, and costs
      were discounted at various rates. Constant 1999 Canadian dollars ($Can) were
      applied, and no increases were assumed over the time horizon of the analysis. A
      multivariate sensitivity analysis with changes in key parameters was also
      performed. RESULTS: From a societal perspective, ropinirole was cost saving. From
      the MoH perspective, the analysis yielded an incremental expected daily
      cost/patient of $Can4.41 for substituting levodopa plus benserazide with
      ropinirole. Ropinirole resulted in daily savings/patient of $Can0.17 in non-drug
      healthcare costs. In the sensitivity analysis, the direction of results did not
      change despite changes of 15 to 20% in key parameters, suggesting robustness of
      the model. CONCLUSIONS: From the societal perspective, in comparison with
      levodopa plus benserazide, the added cost of ropinirole is offset by savings due
      to avoided cases of dyskinesia.

PMID- 12515574
TI  - Economic implications of the use of basiliximab in addition to triple
      immunosuppressive therapy in renal allograft recipients: a UK perspective.
AB  - OBJECTIVE: To compare resource use and costs in renal transplant recipients
      treated with basiliximab or placebo plus triple immunosuppressive therapy.
      DESIGN: International randomised, double-blind, placebo-controlled trial;
      economic evaluation undertaken alongside the efficacy trial. The economic
      evaluation was performed from a UK National Health Service hospital perspective.
      SETTING: 31 centres in 12 countries. PARTICIPANTS: 345 renal transplant
      recipients were enrolled; 340 were randomised (basiliximab 168; placebo 172) and
      included in the intention-to-treat analysis. INTERVENTION: Treatment with placebo
      or basiliximab (20mg intravenous bolus) on day 0 and day 4 after transplantation.
      MAIN OUTCOME MEASURES: Resource utilisation in multiple categories and treatment
      costs for basiliximab and placebo-treated patients during the 6-month post
      transplantation period. RESULTS: No statistically significant differences were
      found in any of the economically important categories of resource use or in the
      mean cost of treatment per person across the whole trial. The mean cost of
      treatment, including the cost of basiliximab, was pound 16 095 for basiliximab
      recipients and pound 15 864 (1997/1998 costs) for placebo recipients, a mean
      difference of pound 231 (95% CI: - pound 1983 to pound 2446), which was not
      significant. Basiliximab treatment led to a significant reduction in acute
      rejection episodes (basiliximab 20.8%; placebo 34.9%; p = 0.005). CONCLUSIONS:
      Basiliximab therapy confers a significant clinical benefit to renal transplant
      recipients without increasing overall treatment costs.

PMID- 12515575
TI  - Cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide
      for reflex sympathetic dystrophy.
AB  - OBJECTIVE: To determine the cost effectiveness and cost utility of acetylcysteine
      versus dimethyl sulfoxide (DMSO) for patients with reflex sympathetic dystrophy
      (RSD), from a societal viewpoint. DESIGN: An economic evaluation was conducted
      alongside a double-dummy, double-blind, randomised, controlled trial. Patients
      were followed for 1 year. The primary outcome measure was the Impairment-level
      Sum Score (ISS). Utilities were determined by the EuroQOL instrument (EQ-5D).
      Both cost-effectiveness and cost-utility analyses were performed. Differences in
      mean direct, indirect and total costs were estimated. Corresponding 95%
      confidence intervals were calculated by bootstrapping techniques. RESULTS: Both
      groups (DMSO, n = 64; acetylcysteine, n = 67) showed relevant improvement; no
      differences in effects were found. Only the total direct costs were significantly
      lower in the DMSO group for the period of 0-52 weeks. The incremental cost
      effectiveness ratios showed that, in general, DMSO generated fewer costs and more
      effects compared with acetylcysteine. Post-hoc subgroup analyses on cost
      effectiveness suggested that patients with warm RSD could be best treated with
      DMSO and patients with cold RSD with acetylcysteine. These results were based on
      small subsamples. CONCLUSION: In general, DMSO is the preferred treatment for
      patients with RSD.

PMID- 12515576
TI  - High-yield expression of properly folded insulinoma-associated protein
      intracellular domain (IA-2ic) in Escherichia coli.
AB  - The intracellular domain of insulinoma-associated protein (IA-2), IA-2ic, is a
      prominent antigen in autoimmune diabetes, and autoantibodies to it are early
      markers of the disease. The high-yield expression of properly folded IA-2ic is
      needed for basic research and crucial for low-cost immunoassays aimed at the
      detection of these autoantibodies in diagnostic and preventive medicine. In
      previous work, the expression of IA-2ic fused to glutathione S-transferase or to
      a biotinylatable peptide was reported; however, these methods had very poor
      yield. Here we show that, utilizing a codon-optimized gene, up to 80 mg of pure
      and properly folded autoantigen per litre of Escherichia coli culture may be
      obtained. Furthermore, the addition of a C-terminal His-tag greatly facilitates
      IA-2ic purification without compromising either its immunoreactivity or its
      expression yield. To take advantage of the recombinant antigen, an enzyme
      immunoassay format was developed which proved to be highly specific and
      sensitive.

PMID- 12515577
TI  - Purification of capsular polysaccharide from Streptococcus pneumoniae serotype
      23F by a procedure suitable for scale-up.
AB  - Streptococcus pneumoniae is a pathogenic encapsulated bacterium, which causes
      pneumonia, bacteraemia and meningitis. Capsular polysaccharide conjugated to a
      carrier protein has been widely used as a vaccine antigen. Serotype 23F is one of
      the prevalent worldwide pneumococci. A simple and efficient method for capsular
      polysaccharide serotype 23F purification that can easily be scaled-up was
      developed. This method consisted of using culture broth obtained by tangential
      microfiltration through a 0.22 microm membrane, broth microfiltrate concentration
      by tangential ultrafiltration in a 30 kDa spiral membrane, fractional ethanol
      precipitation (28-60%), nuclease and proteinase treatment, and
      concentration/diafiltration in a 30 kDa cassette membrane. The final
      polysaccharide recovery was 89%. The final protein and nucleotide contamination
      was 1.5% (w/w) and 0.3% (w/w) respectively. The final pure polysaccharide meets
      the requirements of the World Health Organization and residual proteinase was not
      found in the final product.

PMID- 12515578
TI  - Analysis of nuclear fiber cell compaction in transparent and cataractous diabetic
      human lenses by scanning electron microscopy.
AB  - BACKGROUND: Compaction of human ocular lens fiber cells as a function of both
      aging and cataractogenesis has been demonstrated previously using scanning
      electron microscopy. The purpose of this investigation is to quantify
      morphological differences in the inner nuclear regions of cataractous and non
      cataractous human lenses from individuals with diabetes. The hypothesis is that,
      even in the presence of the osmotic stress caused by diabetes, compaction rather
      than swelling occurs in the nucleus of diabetic lenses. METHODS: Transparent and
      nuclear cataractous lenses from diabetic patients were examined by scanning
      electron microscopy (SEM). Measurements of the fetal nuclear (FN) elliptical
      angles (anterior and posterior), embryonic nuclear (EN) anterior-posterior (A-P)
      axial thickness, and the number of EN fiber cell membrane folds over 20 microns
      were compared. RESULTS: Diabetic lenses with nuclear cataract exhibited smaller
      FN elliptical angles, smaller EN axial thicknesses, and larger numbers of EN
      compaction folds than their non-cataractous diabetic counterparts. CONCLUSION: As
      in non-diabetic lenses, the inner nuclei of cataractous lenses from diabetics
      were significantly more compacted than those of non-cataractous diabetics. Little
      difference between diabetic and non-diabetic compaction levels was found,
      suggesting that diabetes does not affect the degree of compaction. However,
      consistent with previous proposals, diabetes does appear to accelerate the
      formation of cataracts that are similar to age-related nuclear cataracts in non
      diabetics. We conclude that as scattering increases in the diabetic lens with
      cataract formation, fiber cell compaction is significant.

PMID- 12515579
TI  - Temperature differences are associated with malignancy on lung lesions: a
      clinical study.
AB  - BACKGROUND: Although new endoscopic techniques can enhance the ability to detect
      a suspicious lung lesion, the primary diagnosis still depends on subjective
      visual assessment. We evaluated whether thermal heterogeneity of solid tumors, in
      bronchial epithelium, constitutes an additional marker for the diagnosis of
      benign and malignant lesions. METHODS: A new method, developed in our institute,
      is introduced in order to detect temperature in human pulmonary epithelium, in
      vivo. This method is based on a thermography catheter, which passes the biopsy
      channel of the fiber optic bronchoscope. We calculated the temperature
      differences (DeltaT) between the lesion and a normal bronchial epithelium area on
      22 lesions of 20 subjects, 50 - 65 years old. RESULTS: Eleven lesions were benign
      and 11 were malignant, according to the biopsy histology followed the
      thermography procedure. We found significant differences of AT between patients
      with benign and malignant tumor (0.71 +/- 0.6 vs. 1.23 +/- 0.4 degrees C, p <
      0.05). Logistic regression analysis showed that 1-Celsius degree differences
      between normal tissue and suspicious lesion six-fold the probability of
      malignancy (odds ratio = 6.18, 95% CI 0.89 - 42.7). Also, DeltaT values greater
      than 1.05 degrees C, constitutes a crucial point for the discrimination of
      malignancy, in bronchial epithelium, with sensitivity (64%) and specificity
      (91%). CONCLUSION: These findings suggest that the calculated DeltaT between
      normal tissue and a neoplastic area could be a useful criterion for the diagnosis
      of malignancy in tumors of lung lesions.

PMID- 12515580
TI  - A proposed architecture and method of operation for improving the protection of
      privacy and confidentiality in disease registers.
AB  - BACKGROUND: Disease registers aim to collect information about all instances of a
      disease or condition in a defined population of individuals. Traditionally
      methods of operating disease registers have required that notifications of cases
      be identified by unique identifiers such as social security number or national
      identification number, or by ensembles of non-unique identifying data items, such
      as name, sex and date of birth. However, growing concern over the privacy and
      confidentiality aspects of disease registers may hinder their future operation.
      Technical solutions to these legitimate concerns are needed. DISCUSSION: An
      alternative method of operation is proposed which involves splitting the personal
      identifiers from the medical details at the source of notification, and
      separately encrypting each part using asymmetrical (public key) cryptographic
      methods. The identifying information is sent to a single Population Register, and
      the medical details to the relevant disease register. The Population Register
      uses probabilistic record linkage to assign a unique personal identification
      (UPI) number to each person notified to it, although not necessarily everyone in
      the entire population. This UPI is shared only with a single trusted third party
      whose sole function is to translate between this UPI and separate series of
      personal identification numbers which are specific to each disease register.
      SUMMARY: The system proposed would significantly improve the protection of
      privacy and confidentiality, while still allowing the efficient linkage of
      records between disease registers, under the control and supervision of the
      trusted third party and independent ethics committees. The proposed architecture
      could accommodate genetic databases and tissue banks as well as a wide range of
      other health and social data collections. It is important that proposals such as
      this are subject to widespread scrutiny by information security experts,
      researchers and interested members of the general public, alike.

PMID- 12515581
TI  - Identification of three novel OA1 gene mutations identified in three families
      misdiagnosed with congenital nystagmus and carrier status determination by real
      time quantitative PCR assay.
AB  - BACKGROUND: X-linked ocular albinism type 1 (OA1) is caused by mutations in OA1
      gene, which encodes a membrane glycoprotein localised to melanosomes. OA1 mainly
      affects pigment production in the eye, resulting in optic changes associated with
      albinism including hypopigmentation of the retina, nystagmus, strabismus, foveal
      hypoplasia, abnormal crossing of the optic fibers and reduced visual acuity.
      Affected Caucasian males usually appear to have normal skin and hair pigment.
      RESULTS: We identified three previously undescribed mutations consisting of two
      intragenic deletions (one encompassing exon 6, the other encompassing exons 7-8),
      and a point mutation (310delG) in exon 2. We report the development of a new
      method for diagnosis of heterozygous deletions in OA1 gene based on measurement
      of gene copy number using real-time quantitative PCR from genomic DNA.
      CONCLUSION: The identification of OA1 mutations in families earlier reported as
      families with hereditary nystagmus indicate that ocular albinism type 1 is
      probably underdiagnosed. Our method of real-time quantitative PCR of OA1 exons
      with DMD exon as external standard performed on the LightCycler trade mark allows
      quick and accurate carrier-status assessment for at-risk females.

PMID- 12515582
TI  - Algorithms for computing parsimonious evolutionary scenarios for genome
      evolution, the last universal common ancestor and dominance of horizontal gene
      transfer in the evolution of prokaryotes.
AB  - BACKGROUND: Comparative analysis of sequenced genomes reveals numerous instances
      of apparent horizontal gene transfer (HGT), at least in prokaryotes, and
      indicates that lineage-specific gene loss might have been even more common in
      evolution. This complicates the notion of a species tree, which needs to be re
      interpreted as a prevailing evolutionary trend, rather than the full depiction of
      evolution, and makes reconstruction of ancestral genomes a non-trivial task.
      RESULTS: We addressed the problem of constructing parsimonious scenarios for
      individual sets of orthologous genes given a species tree. The orthologous sets
      were taken from the database of Clusters of Orthologous Groups of proteins
      (COGs). We show that the phyletic patterns (patterns of presence-absence in
      completely sequenced genomes) of almost 90% of the COGs are inconsistent with the
      hypothetical species tree. Algorithms were developed to reconcile the phyletic
      patterns with the species tree by postulating gene loss, COG emergence and HGT
      (the latter two classes of events were collectively treated as gene gains). We
      prove that each of these algorithms produces a parsimonious evolutionary
      scenario, which can be represented as mapping of loss and gain events on the
      species tree. The distribution of the evolutionary events among the tree nodes
      substantially depends on the underlying assumptions of the reconciliation
      algorithm, e.g. whether or not independent gene gains (gain after loss after
      gain) are permitted. Biological considerations suggest that, on average, gene
      loss might be a more likely event than gene gain. Therefore different gain
      penalties were used and the resulting series of reconstructed gene sets for the
      last universal common ancestor (LUCA) of the extant life forms were analysed. The
      number of genes in the reconstructed LUCA gene sets grows as the gain penalty
      increases. However, qualitative examination of the LUCA versions reconstructed
      with different gain penalties indicates that, even with a gain penalty of 1
      (equal weights assigned to a gain and a loss), the set of 572 genes assigned to
      LUCA might be nearly sufficient to sustain a functioning organism. Under this
      gain penalty value, the numbers of horizontal gene transfer and gene loss events
      are nearly identical. This result holds true for two alternative topologies of
      the species tree and even under random shuffling of the tree. Therefore, the
      results seem to be compatible with approximately equal likelihoods of HGT and
      gene loss in the evolution of prokaryotes. CONCLUSIONS: The notion that gene loss
      and HGT are major aspects of prokaryotic evolution was supported by quantitative
      analysis of the mapping of the phyletic patterns of COGs onto a hypothetical
      species tree. Algorithms were developed for constructing parsimonious
      evolutionary scenarios, which include gene loss and gain events, for orthologous
      gene sets, given a species tree. This analysis shows, contrary to expectations,
      that the number of predicted HGT events that occurred during the evolution of
      prokaryotes might be approximately the same as the number of gene losses. The
      approach to the reconstruction of evolutionary scenarios employed here is
      conservative with regard to the detection of HGT because only patterns of gene
      presence-absence in sequenced genomes are taken into account. In reality,
      horizontal transfer might have contributed to the evolution of many other genes
      also, which makes it a dominant force in prokaryotic evolution.

PMID- 12515583
TI  - No simple dependence between protein evolution rate and the number of protein
      protein interactions: only the most prolific interactors tend to evolve slowly.
AB  - BACKGROUND: It has been suggested that rates of protein evolution are influenced,
      to a great extent, by the proportion of amino acid residues that are directly
      involved in protein function. In agreement with this hypothesis, recent work has
      shown a negative correlation between evolutionary rates and the number of protein
      protein interactions. However, the extent to which the number of protein-protein
      interactions influences evolutionary rates remains unclear. Here, we address this
      question at several different levels of evolutionary relatedness. RESULTS:
      Manually curated data on the number of protein-protein interactions among
      Saccharomyces cerevisiae proteins was examined for possible correlation with
      evolutionary rates between S. cerevisiae and Schizosaccharomyces pombe orthologs.
      Only a very weak negative correlation between the number of interactions and
      evolutionary rate of a protein was observed. Furthermore, no relationship was
      found between a more general measure of the evolutionary conservation of S.
      cerevisiae proteins, based on the taxonomic distribution of their homologs, and
      the number of protein-protein interactions. However, when the proteins from yeast
      were assorted into discrete bins according to the number of interactions, it
      turned out that 6.5% of the proteins with the greatest number of interactions
      evolved, on average, significantly slower than the rest of the proteins.
      Comparisons were also performed using protein-protein interaction data obtained
      with high-throughput analysis of Helicobacter pylori proteins. No convincing
      relationship between the number of protein-protein interactions and evolutionary
      rates was detected, either for comparisons of orthologs from two completely
      sequenced H. pylori strains or for comparisons of H. pylori and Campylobacter
      jejuni orthologs, even when the proteins were classified into bins by the number
      of interactions. CONCLUSION: The currently available comparative-genomic data do
      not support the hypothesis that the evolutionary rates of the majority of
      proteins substantially depend on the number of protein-protein interactions they
      are involved in. However, a small fraction of yeast proteins with the largest
      number of interactions (the hubs of the interaction network) tend to evolve
      slower than the bulk of the proteins.

PMID- 12515584
TI  - Endemic cryptosporidiosis and exposure to municipal tap water in persons with
      acquired immunodeficiency syndrome (AIDS): a case-control study.
AB  - BACKGROUND: In persons with acquired immunodeficiency syndrome (AIDS),
      Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which
      there is no effective treatment, and the risk of developing cryptosporidiosis
      from drinking tap water in non-outbreak settings remains uncertain. To test the
      hypothesis that drinking tap water was associated with developing
      cryptosporidiosis, we conducted a matched case-control study among persons with
      AIDS in San Francisco. METHODS: Among patients reported to the San Francisco AIDS
      Registry from May 1996 through September 1998, we compared patients who developed
      cryptosporidiosis to those who did not. Cases were individually matched to
      controls based on age, sex, race/ethnicity, CD4+ T lymphocyte count, date of CD4+
      count, and date of case diagnosis. Population attributable fractions (PAFs) were
      calculated. RESULTS: The study consisted of 49 cases and 99 matched controls. In
      the multivariable analysis with adjustments for confounders, tap water
      consumption inside and outside the home at the highest exposure categories was
      associated with the occurrence of cryptosporidiosis (inside the home: odds ratio
      (OR), 6.76; 95% CI 1.37-33.5, and outside the home: OR 3.16; 95% CI 1.23-8.13).
      The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San
      Francisco AIDS patients attributable to tap water consumption could have been as
      high as 85%. CONCLUSIONS: Although the results from this observational study
      cannot be considered definitive, until there is more data, we recommend persons
      with AIDS, especially those with compromised immune systems, consider avoiding
      tap water.

PMID- 12515585
TI  - The effect of ketotifen on inflammatory markers in allergic conjunctivitis: an
      open, uncontrolled study.
AB  - BACKGROUND: The efficacy and safety of ketotifen eye drop treatment in allergic
      conjunctivitis (AC) management is perfectly known by several studies, but the
      mechanism of action at the biochemical levels is poorly understood so we decided
      to perform an open, uncontrolled study in order to investigate the effect of the
      topical administration of ketotifen fumarate 0.05% on biochemical markers of
      inflammation on conjunctival cells in patients with AC. METHODS: Nineteen
      patients with symptoms and signs of AC (itching, discharge, burning, redness,
      increase in the watery discharge, swelling and follicles) and with a history of
      allergy were prescribed with two daily instillation of one drop of eyewash
      ketotifen fumarate 0,05% in both eyes during thirty days. They were studied by
      measuring clinical and immunologic parameters. RESULTS: Ketotifen fumarate
      treatment significantly reduced the total symptoms and signs score for each
      patient as well as each symptoms and signs at all time points compared with day 0
      (p < 0.0001 and p < 0.016, respectively). Although the percentage of HLA-DR+
      epithelial cells diminished only in 58% of patients, the numbers of CD29+ and
      eotaxin+ epithelial cells dropped significantly in 68% and 73 % of them (p <
      0.0062 and <0.0082, respectively) as a consequence of the treatment. In 9 out of
      19 patients a simultaneous decrease in the percentage of epithelial cells
      positive for CD29 and eotaxin was observed. CONCLUSION: Ketotifen besides the
      well-known effect in reducing signs and symptoms of AC significantly diminished
      production of eotaxin and expression of CD29 by epithelial cells in patients with
      seasonal AC.

PMID- 12515586
TI  - Possible range of dioxin concentration in human tissues: simulation with a
      physiologically based model.
AB  - In risk evaluation of dioxins, monitoring chemical concentrations in human
      tissues is an important step, and these concentration data can be utilized along
      with animal toxicity data for extrapolation of human manifestation. However large
      differences in dioxin concentrations usually exist even among individuals who
      have never been accidentally exposed to high quantities of dioxin, and this may
      cause problems in risk analysis. Body size, age, and history of food consumption
      are factors responsible for these interindividual differences in addition to
      exposure levels. Using a physiologically based pharmacokinetic (PBPK) model, the
      influence of differences in body weight, gastrointestinal absorption, and half
      life and intake of dioxin were examined on tissue chemical concentration. Dioxin
      concentrations over a 40-yr time course in human liver, kidneys, fat, blood,
      muscle and richly perfused tissue were simulated for polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar
      polychlorinated biphenyls (CoPCBs). Model parameters such as tissue-blood
      partition coefficients for CoPCBs were prepared, and sensitivity analysis was
      also performed on these parameters. The range of tissue concentrations was
      approximately 0.17 to 4.1 times the standard concentration, which was calculated
      using standard model parameters. The simulated ranges included more than 80% of
      the individual anatomical data for 2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,
      pentachlorodibenzo-p-dioxin, and 3,3',4,4',5-pentachlorobiphenyl in liver, fat,
      and blood. These results suggest that differences in body weight,
      gastrointestinal absorption, and food intake behavior may partially explain
      variation in tissue concentrations among individuals, and the possible
      interindividual uncertainty, which is approximately 24 for the general Japanese
      population.

PMID- 12515587
TI  - Route-of-entry and brain tissue partition coefficients for common superfund
      contaminants.
AB  - Various organic solvents may be encountered in contaminated water supplies at
      U.S. Environmental Protection Agency-designated Superfund sites. Human exposure
      to these environmental contaminants may occur by oral, dermal, or inhalation
      routes. The estimation of human health risk associated with exposure to these
      solvents can be improved through the use of physiologically based pharmacokinetic
      (PBPK) models to describe the absorption, tissue distribution, metabolism, and
      elimination of the compounds following any route of exposure. However,
      development of these PBPK models requires information on the relative solubility,
      or partition coefficient, of each compound in blood and various tissues. A number
      of investigators have provided partition coefficient information on different
      tissues in various species; however, the data for route of entry organs (i.e.,
      skin, lung, stomach) and brain tissue are not complete. Therefore, the objective
      of this work was to replicate partition coefficient studies for several commonly
      encountered environmental contaminants using an in vitro gas-phase vial
      equilibration technique and to include tissues to evaluate brain, lung, stomach,
      and skin. A comparison of the partition coefficient values determined here with
      values reported in the literature, where available, showed good agreement in
      nearly all cases. An additional study was conducted to compare the liver-to-air
      partition coefficient values for toluene, benzene, and o-xylene introduced as
      single chemicals to partition coefficient values determined with the chemicals
      introduced as a mixture of all three compounds. The similarities of the resulting
      values suggest that both labor and laboratory resources may be reduced when
      partition coefficients are determined as chemical mixtures.

PMID- 12515588
TI  - Evaluation of the dermal absorption of aqueous toluene in F344 rats using real
      time breath analysis and physiologically based pharmacokinetic modeling.
AB  - Toluene is a ubiquitous chemical that is commonly used for its solvent properties
      in industry and manufacturing, and is a component of many paint products. Because
      of its widespread use, there is potential for both occupational and
      nonoccupational dermal exposure to toluene. To understand the significance of
      these exposures, the dermal bioavailability of toluene was assessed in F344 male
      rats using a combination of real-time exhaled breath analysis and physiologically
      based pharmacokinetic (PBPK) modeling. Animals were exposed to toluene at 0.5 or
      0.2 mg/ml aqueous concentration (0.05% or 0.02%) using a 2.5-cm-diameter occluded
      glass patch system attached to a clipper-shaved area on the back of the rat.
      Immediately following exposure, individual animals were placed in a glass off
      gassing chamber and exhaled breath was monitored as chamber concentration in real
      time using an ion-trap mass spectrometer (MS/MS). The real-time exhaled breath
      profile clearly demonstrated the rapid absorption of toluene, with peak chamber
      concentrations observed within 1 h from the start of exposure. The PBPK model
      describing the exposure and off-gassing chamber was used to estimate a dermal
      permeability coefficient (K(p)) to describe each set of exhaled breath data.
      Regardless of exposure level, a single K(p) value of 0.074 +/- 0.005 cm/h
      provided a good fit to all data sets. These rat studies using aqueous toluene
      will form the basis for comparing the dermal bioavailability of toluene in
      various paint products and may ultimately aid in understanding human health risk
      under a variety of exposure scenarios.

PMID- 12515589
TI  - Disposition of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5h)-furanone (mx) in
      b6c3f1 mice and f344 rats.
AB  - 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a mutagenic by
      product of chlorination of drinking water, particularly where the water contains
      humic matter. MX has been estimated to account for 50% of the mutagenic activity
      in some drinking water. A bioassay in rats demonstrated an increased tumor
      incidence, primarily in liver and thyroid glands. This study was designed to
      provide disposition/metabolism information in mice to evaluate the necessity of a
      National Toxicology Program chronic bioassay and to provide data for female rats.
      Radioactivity was rapidly absorbed and excreted near equally in urine (42-54%)
      and feces (40-51%) 72 h following oral administration of (14)C-labeled MX at
      single doses from 0.2 to 20 mg/kg to male and female mice and female rats. A
      larger percentage (71-73%) of MX-derived radioactivity was excreted in urine
      after an iv dose (0.2 mg/kg) in both female rats and male mice. Most MX-derived
      radioactivity was excreted within the first 24 h postdosing. MX was transformed
      to urinary and biliary metabolites. A major extremely polar urinary metabolite
      was tentatively identified as 1-hydroxy-1,2,2-ethanetricarboxylic acid. This
      metabolite is likely transformed from the MX degradation product 2-hydroxy-3
      formyl-4-oxo-2-butenoic acid. Oral administration produced highest tissue/blood
      ratios in the following order: forestomach (>100), glandular stomach, intestine,
      and kidney. Intravenous administration resulted in high, prolonged levels of
      radioactivity in blood compared to oral dosing. Therefore, MX disposition appears
      to be dominated by its chemical reactivity with highest concentrations of
      radioactivity being found at the site of administration.

PMID- 12515590
TI  - Effects of in utero and lactational ammonium perchlorate exposure on thyroid
      gland histology and thyroid and sex hormones in developing deer mice (peromyscus
      maniculatus) through postnatal day 21.
AB  - Thyroid gland hormone levels and histology and sex hormone levels in developing
      deer mice (Peromyscus maniculatus) were measured following in utero and
      lactational exposure to ammonium perchlorate (AP), a component of rocket fuel and
      a thyroid toxicant. Breeding pairs were dosed continuously with 0, 1 nM, 1 micro
      M, or 1 mM concentrations of AP in drinking water from the time of cohabitation
      until pups from the third litter were weaned. Pups from the second litter were
      used for evaluation in this study. The active (colloid-containing) thyroid
      follicle number per unit area was significantly different between treatment
      groups. The 1-nM and 1-mM treatment groups had significantly fewer active
      follicles per unit area than did controls. The 1-mM treatment group also had
      significantly fewer active follicles than the 1- micro M and the 1-nM treatment
      groups. Total T(4) concentrations were significantly increased in the 1-nM and 1-
      micro M groups compared to the controls. No significant difference was observed
      in total T(3) concentrations. None of the 1-mM plasma had concentrations of total
      testosterone above the detection limit, and only one of the 1- micro M samples
      was above the detection limit of the assay. All estradiol concentrations were
      below the detection limits of the assay. In contrast to the situation in adult
      rodents, it appears that AP increases thyroid hormone production in developing
      deer mice and produces variable effects with increasing concentrations.

PMID- 12515591
TI  - Proto-oncogene amplification and overexpression in cadmium-induced cell
      transformation.
AB  - Cadmium (Cd) is an essential material used in the battery, metal-coating, and
      alloy industries. In addition to these industrial uses, it is also a component of
      cigarette smoke. Therefore, exposure to cadmium is widespread and presents a
      considerable health concern. Cadmium is known to be a carcinogen; however, the
      possible mechanism of carcinogenesis with regards to the activation and
      inactivation of cancer-related genes has not yet been fully elucidated. In this
      study, amplification, expression, and point mutation of cancer-related genes
      associated with Cd-induced cell transformation in BALB/c-3T3 cells were studied.
      Six proto-oncogenes (K-ras, c-myc, c-fos, c-jun, c-sis, and erbB), as well as the
      p53 tumor suppressor, were investigated for gene amplification using differential
      polymerase chain reaction (PCR), while the expression of the proteins produced by
      these genes was evaluated by Western blot analysis. Point mutations in K-ras and
      p53 were studied by PCR restriction fragment length polymorphism analysis and DNA
      sequencing. There were no point mutations observed in codons 12, 13, and 61 of K
      ras or in exons 4-10 of p53 and no observed differences in the levels of any of
      the proteins studied. Among 10 Cd-induced transformed cell lines, significant
      gene amplification was found for c-myc and c-jun in 50% and 80% of the cell
      lines, respectively. Chromosome painting was performed to confirm that this
      amplification was not simply due to additional copies of the chromosomes carrying
      these oncogenes. In addition, reverse-transcription PCR (RT-PCR) was performed to
      confirm increased expression of c-myc and c-jun. These results suggest that cell
      transformation induced by Cd may be attributed, at least in part, to gene
      amplification of c-myc and c-jun and that some of the Cd-transformed cells may
      possess neoplastic potential resulting from genomic instability.

PMID- 12515592
TI  - Assessment of health and growth of ring-necked pheasants following consumption of
      infected insects or conidia of entomopathogenic fungi, Metarhizium anisopliae
      var. acridum and Beauveria bassiana, from Madagascar and North America.
AB  - Isolates of two fungi (Beauveria bassiana and Metarhizium anisopliae var.
      acridum) from Madagascar are being developed for control of grasshoppers and
      locusts, as part of a search for alternatives to environmentally detrimental
      chemical insecticides. The probable effects of these entomopathogens on nontarget
      species must be determined before operational use. Birds may become exposed to
      these fungi either directly, by consuming spores deposited on their food items,
      or secondarily, by consuming grasshoppers or locusts that have died from
      infection by these biocontrol agents. This article presents the results of per os
      challenge from fungus-infected food items. Male and female ring-necked pheasants
      (Phasianus colchicus) were exposed at 4 d of age and again at 9 d of age to
      challenge treatments, or 2 control treatments (18 male and 18 female birds per
      treatment group). Pheasants were weighed at 9, 17, and 25 d of age, tarsal length
      was measured at 25 d of age, and they were observed daily for signs of adverse
      effects of the experimental treatments. At the time of euthanasia (25 d of age),
      2 or 3 randomly selected birds from each of the groups exposed to infected
      grasshoppers, plus the 2 control groups, underwent complete necropsies and
      histopathological examination of 16 tissues from each bird. Results show that in
      both sexes, weight gain at both 17 and 25 d was not significantly different
      between challenge groups and control groups. Tarsal length at 25 d of age, an
      indication of structural growth, was also not markedly different among challenged
      and control groups. Histopathological changes were generally undetectable, mild,
      or moderate, and not consistently associated with any treatment. Based on these
      findings, there is little indication that birds are susceptible to detrimental
      health effects from direct or secondary exposure to the two entomopathogenic
      fungi studied.

PMID- 12515593
TI  - Metabolism of territrem a in liver microsomes from male wistar rats: 3.
      Cytochrome p-450 isoforms catalyzing tra metabolism.
AB  - The cytochrome P-450 isoforms involved in territrem A (TRA) metabolism in liver
      microsomes of male Wistar rats have been characterized. Pretreatment with
      phenobarbital (PB) or dexamethasone (DEX) resulted in a similar significant
      increase in TRA metabolic activity. Although PB treatment resulted in a
      significant elevation in CYP2B, CYP2C11, and CYP3A levels, only CYP3A levels were
      significantly increased by DEX treatment. Cimetidine markedly reduced the
      formation of the TRA metabolites 4beta-hydroxymethyl-4beta-demethylterritrem A
      (MA(1)), 4beta-oxo-4beta-demethylterritrem A (MAX) and 2-dihydro-4beta
      demethylterritrem A (MA(2)) in liver microsomes from 2-wk-old rats (mainly
      containing CYP3A2) and 7-wk-old rats (containing CYP2B, CYP2C11, and CYP3A2). SKF
      525A, which inhibits CYP2B, CYP2C11, and CYP3A2, and orphenadrine, which inhibits
      CYP2B, also decreased MA(2) formation in liver microsomes from 7-wk-old
      phenobarbital-pretreated rats. The formation of MA(1) and MAX was not affected.
      Furthermore, an immunoinhibition study demonstrated that anti-CYP3A2 antibody
      reduced MA(1), MAX, and MA(2) formation to nondetectable levels in liver
      microsomes from 2- and 7-wk-old rats, whereas anti-CYP2C11 or anti-CYP2B
      antibody, respectively, had no marked effect on MA(1), MAX, and MA(2) formation
      in liver microsomes from 7-wk-old untreated or PB-treated rats. These results
      suggest that the CYP3A isoform is mainly responsible for MA(1), MAX, and MA(2)
      formation in liver microsomes in male Wistar rats.

PMID- 12515608
TI  - [Connexin 43 gene in the in vivo treatment of cerebral glioma in C6 rats].
AB  - OBJECTIVE: To study the role of connexin gene (Cx43) in the suppression of C6
      glioma. METHODS: Cx43 gene depleted parental C6 rats (control group) and C6 cells
      transfected with Cx43 cDNA (transfection group) were implanted into the right
      caudate nucleus of SD rats. Rats bearing cerebral C6 gliomas were treated with
      Cx43 cDNA (treatment group) with another group treated with empty vector (empty
      vector group) serving as control. The general manifestation, survival time, MRI
      dynamic scanning and histopathological changes in all rats were observed. Cx43
      mRNA and its protein were examined by in situ hybridization and
      immunohistochemistry. Proliferation activity was monitored by the average number
      of AgNOR stain. Cell apoptosis was examined by the Tolt-mediated x-duTP nick end
      labeling (TUNEL) method. RESULTS: All rats in the control and empty vector groups
      died of cerebral glioma within 3 weeks after implantation of C6 cells. Six in the
      transfection group and 8 in the treatment group were alive beyond 120 days with
      complete disappearance of the tumor foci, except one in this group having some
      residue of tumor. In the glioma of transfection and treatment groups, Cx43 gene
      expression was up-regulated, proliferation activity reduced while the apoptotic
      cells did not increase. CONCLUSION: The development of glioma is greatly
      suppressed by the transfection of Cx43 gene, which has great effectiveness in
      rats bearing cerebral malignant gliomas. This could become a target of choice in
      the gene treatment of malignant gliomas.

PMID- 12515609
TI  - [Unscheduled expression of cyclin B1 in G(1)-phase among cultured and clinical
      tumor cells].
AB  - OBJECTIVE: To confirm the unscheduled in vivo and in vitro expression models of
      cyclin B1 in cancer cells so as to study the different profiles of cyclin B1 in
      G(1)-phase immortal cells under different culture states and culture conditions.
      METHODS: Multiparameter flow cytometry (FCM) was used to correlate the expression
      of cyclin B1 with the position in cell cycle of immortal cells in vivo and in
      vitro using the MOLT-4 cell line as control. Cells which belonged to G(1)-phase
      were sorted by FCM according DNA diploidy, and then the expression of cyclin B1
      was examined by confocal microscope to confirm the results. For further analysis,
      different subgroups in G(1) phase were sorted according to the fluorescent
      intensity of cyclin E, and then the exact period in G(1) phase when cyclin B1 was
      expressed, were assayed by Western blot. RESULTS: Unscheduled expression of
      cyclin B1 expressed in G(1)-phase was found not only in synchronized leukemia
      cells MOLT-4 and in vivo transformed T-7 cells, but also in vivo tumor cells
      detached from clinical samples. In the synchronized growing cells, cyclin B1 was
      mainly detected in the early G(1) phase, while in transformed T7 cells, cyclin B1
      was mainly detected in the late G(1) phase. CONCLUSION: The limitation of
      detecting cyclin B1 is due to its unscheduled expression, rending cyclin B1 being
      detected at different time-spots in the G(1) phase. This phenomenon may be
      related to the adjustment between the loss of control in cell proliferation and
      cell apoptosis, thereby leading to tumorigenesis.

PMID- 12515610
TI  - [Search for interacting proteins of esophageal cancer related gene-1 encoded
      protein through the yeast two-hybrid system].
AB  - OBJECTIVE: To understand the role that esophageal cancer related gene-1 (ECRG-1)
      plays and to search for ECRG-1-interacting proteins. METHODS: A DNA fragment
      encoding the carboxy-terminus of ECRG-1 (amino acids 40 - 418) was inserted into
      pGBKT7-DNA-BD vector and fused in-frame to the DNA-binding domain of GAL4. Then,
      it was used as a bait to screen the human fetal liver cDNA library by yeast two
      hybrid, with the cDNA fragment inserted into pACT2 vector and fused in-frame to
      the Gal4 activation domain. If ECRG-1 interacted with a protein encoded by a cDNA
      fragmant in the yeast, the transcription of reporter Gene could be activated.
      With the false positive clonies eliminated, the inserts in the positive plasmids
      were sequenced and compared to those in the GenBank. RESULTS: In approximately 3
      x 10(6) independent tansformants screened, 23 clonies exhibited the expression of
      reporter gene. After eliminating the false positive clonies, two cDNA fragments
      were obtained. DNA sequencing revealed that one encoded Miz-1 (Myc-interacting Zn
      finger protein-1), and another encoded FLNA (actin-binding protein-280), Miz-1,
      being a Zn finger protein, could be bound to p15 promotor and activated the
      transcription. FLNA, being an actin-binding protein took part in the TGF-beta
      pathway via interaction with Smad. CONCLUSION: ECRG-1 is able to be specifically
      bound to Miz-1 and FLNA in the yeast. It may play a role in the regulation of
      cell cycle via interaction with Miz-1 and FLNA.

PMID- 12515611
TI  - [cDNA array in the establishment of a gene expression profile associated with
      differentiation inducing the glioma cells].
AB  - OBJECTIVE: Establishment of a gene expression profile associated with
      differentiation inducing the glioma cells was made possible. METHOD: The
      expression level of 18 000 genes in glioma cells was evaluated before and after
      induction with sodium phenyl-butyrate for 2 hours or 6 days by cDNA array
      technique, with the results proved by multi-dot blot. RESULTS: Ninety-eight gene
      expressions in the glioma cells were changed after the induction, with some genes
      in transcription and translation systems down-regulated, some oncogenes down
      regulated, and some differentiation or apoptosis genes up-regulated. Eighteen
      unknown EST fragments were changed also. CONCLUSION: A gene expression profile
      associated with differentiation-inducing the glioma cells including 98 genes has
      been established.

PMID- 12515612
TI  - [EB virus encoded latent membrane protein 1 modulates the phosphorylation of
      epidermal growth factor receptor in nasopharyngeal carcinoma cell line].
AB  - OBJECTIVE: To elucidate the regulation of the phosphorylation of epidermal growth
      factor receptor (EGFR) by the EB virus encoded latent membrane protein 1 (LMP1)
      in nasopharyngeal carcinoma cell line. METHODS: The levels of EGFR expression and
      phosphorylation in pTet-on LMP1 HNE2 cell, a nasopharyngeal carcinoma (NPC) cell
      line, in the dynamic expression of LMP1 induced by different concentrations of
      doxycycline (Dox) were observed. The EGFR dominant negative mutant and LMP1
      antisense expression plasmid were transiently transfected into pTet-on LMP1 HNE2
      cells by lipofectamine, and the changes in EGFR phosphorylation were observed by
      immunocoprecitation and Western blot. The changes in EGFR phosphorylation were
      observed after EGF treatment. RESULTS: In pTet-on LMP1 HNE2 cells, Dox-induced
      LMP1 upregulated EGFR expression and phosphorylation in a dose-dependent manner.
      After EGFR dominant negative mutant was transfected into pTet-on LMP1 HNE2 cells,
      the increase of EGFR phosphorylation was inhibited completely. When LMP1
      antisense expression plasmid was transfected into pTet-on LMP1 HNE2 cells, the
      levels of EGFR phosphorylation were also inhibited significantly. Meanwhile,
      after EGF had been added into pTet-on LMP1 HNE2 cells, increase of EGFR
      phosphorylation was induced, but it was completely blocked by EGFR dominant
      negative mutant and the introduction of LMP1 antisense. CONCLUSION: EB virus
      encoded LMP1 not only induces the dose-dependent expression of EGFR, but also the
      dose-dependent phosphorylation of EGFR. The phosporylation of EGFR may play a
      vital role in the development of nasopharyngeal carcinoma.

PMID- 12515613
TI  - [Influence of 4-aminopyridine on voltage-activated K(+) current and cell
      proliferation in small cell lung cancer].
AB  - OBJECTIVE: To study the inhibition of voltage-activated K(+) conductance and cell
      proliferation by 4-aminopyridine (4-AP) in the human small-cell lung cancer
      (SCLC). METHODS: Inhibition of voltage-activated K(+) current by 4-AP through the
      whole-cell patch-clamp technique in SCLC cell line was studied. The influence on
      the cell-cycle by 4-AP was observed by flow cytometry to identify the in vitro
      inhibition by 4-AP to the cell proliferation of the SCLC cell line. RESULTS:
      Exposure of the tumor cells to 5 mmol/L 4-AP reduced the peak outward K(+)
      current (evoked by a depolarization to +80 mV) from 1.22 +/- 0.11 nA (n = 30) to
      0.59 +/- 0.10 nA (n = 28). Flow cytometry results showed that cell population
      accumulated in the G(0)/G(1) phase and a significantly reduced proportion in the
      S phase and G(1)/G(2) phase cells after having been exposed to 4-AP for three
      days. Incubation of the SCLC cells with 0.1, 5, 10, 15, 20 mmol/L 4-AP resulted
      in a concentration-and time-dependent reduction in the number of viable cells as
      compared with the control. CONCLUSION: The voltage-activated K(+) channels
      expressed by SCLC play an important role in SCLC cell proliferation. The
      proliferation of the SCLC cells is inhibited by K(+) channel antagonists.

PMID- 12515614
TI  - [Establishment and characteristics of orthotopically transplanted model of human
      primary malignant spleen lymphoma in nude mice].
AB  - OBJECTIVE: To establish three orthotopically transplanted model of human primary
      malignant spleen lymphoma in the nude mice. METHODS: Orthotopic transplantation
      of histologically intact human primary malignant splenic lymphoma tissue obtained
      from patients was introduced into the splenic parenchyma of nude mice.
      Tumorigenicity, invasion, metastasis and morphological characteristics of the
      transplanted tumor were studied by light microscopy, electron microscopy and
      immunohistochemical methods. RESULTS: The first kind, a strain of human primary
      malignant spleen lymphoma (non-Hodgkin's, cleaved B cell, BFNHL-HMN-1) screened
      from 11 patients which had been passaged in vivo for 41 generations, a second
      kind, a liver metastasis model of human primary malignant spleen lymphoma (non
      Hodgkin's, cleaved B cell, LM-BFNHL-HMN-2) which had been passaged for 47
      generations and a third kind of human primary malignant spleen lymphoma (non
      Hodgkin's, T-immunoblastic cell, TINHL-HMN-3) having passaged for 37 generations
      were all successfully transplanted in 611 nude mice. Models of BFNHL-HMN-1 and
      TINHL-HMN-3 tumor gave nodular growth and lymph node metastasis in the spleen
      hilum but without any metastasis in the abdominal lymph nodes or organs. In the
      LM-BFNHL-HMN-2 model, not only did the tumor cells grow in the spleen, but in
      spleen hilum, lymph nodes and liver also. The orthotopically transplanted tumor
      cells were similar to the original human tumor in light histopathology,
      ultrastructure features, DNA content and chromosomal karyotype. CONCLUSION: These
      three models are able to serve as useful tools for the study of biologic
      characteristics and experimental treatment of human primary malignant lymphoma.

PMID- 12515615
TI  - [Cloning of differentially expressed cDNA sequences involved in malignant
      transformation induced by benzo(a)pyrene metabolite dihydroxyepoxy benzo pyrene].
AB  - OBJECTIVE: To clone differentially expressed cDNA sequences involved in malignant
      transformation induced by benzo(a)pyrene metabolite dihydroxyepoxy benzo pyrene
      (BPDE). METHOD: The malignant transformation of human bronchial epithelial cell
      line 16HBE induced by BPDE in vitro was used as a model for comparing gene
      expression between the transformed cells and controls. cDNA representational
      difference analysis (cDNA-RDA) was performed to isolate differentially expressed
      cDNA fragment in transformed cells. The cDNA fragments were ligated to pGEM-T
      vector and transformed into JM109 bacteria. The plasmid DNA were sequenced and
      compared with data in GenBank by BLASTN. RESULTS: Five cDNA sequences were found
      to be novel ones and were registered in dbest database, which assigned accession
      numbers in GenBank are BG354691, BG354692, BG354693, BG354694 and BG354695,
      respectively. Eight of the remaining cDNA sequences showed sequence homology to
      those previously reported such as ribosomal protein S23, MLN137, ACTN4,
      transforming growth factor and G protein gene. CONCLUSIONS: These 13 genes may be
      involved in BPDE-induced malignant transformation, but their biological
      characteristics and functions are left to further studies.

PMID- 12515616
TI  - [cDNA microarray in the gene expression pattern in lymphatic metastasis of
      pancreatic carcinoma].
AB  - OBJECTIVE: Analysis of differential gene expression profiles by cDNA microarray
      in pancreatic carcinoma with or without lymphatic metastasis. METHODS: cDNA
      microarray was prepared by spotting polymerase chain reaction (PCR) products of 4
      000 human genes onto specially treated glass slides. The cDNA probes were
      prepared by labeling normal tissue mRNA and cancer tissue mRNA with Cy3-dUTP and
      Cy5-dUTP, separately through reverse transcription. The mixed probes were, then,
      hybridized to the cDNA microarray. The chips were scanned by ScanArray 3000 laser
      scanner (General Scanning, Inc) on two wavelengths. The acquired image was
      analyzed by ImaGene 3.0 software (BioDiscovery, Inc). The intensity of each spot
      on the two wavelengths represented the quantity of Cy3-dUTP and Cy5-dUTP, with
      Cy5 to Cy3 ratio computed on each. RESULTS: Fifty-six genes (including 24
      previously reported) exhibited differential expressions in 2 specimens of
      pancreatic carcinoma with lymphatic metastasis and 2 without. CONCLUSION: cDNA
      microarray provides an promising approach to specific gene expressions of the
      presence of lymphatic metastasis in human pancreatic carcinoma.

PMID- 12515617
TI  - [Gene diagnosis and prognosis of mediastinal lymph node occult micrometastasis in
      non-small cell lung carcinoma].
AB  - OBJECTIVE: To investigate gene diagnosis of occult micrometastasis in the
      mediastinal lymph node in patients with non-small cell lung carcinoma (NSCLC) and
      to evaluate its prognostic significance. METHODS: With mRNA expression of mucoid1
      (MUC1) gene examined by RT-PCR, 168 mediastinal lymph nodes taken from 37 pN(0)
      (negative lymph nodes) NSCLC patients (stage Ia approximately IIb) made up the
      experiment group. Thrity negative lymph nodes from 14 benign lesions and 30
      positive lymph nodes from 15 NSCLC patients served as control. The survival
      difference between MUC1 mRNA-negative and MUC1 mRNA-positive groups was compared
      by the chi(2) test. RESULTS: UC1 mRNA was not identified in the negative-control
      group (specificity = 100%), but it was identified in 26 of 30 positive-control
      samples (sensitivity = 86.7%). MUC1 mRNA was identified in 16 (9.5%) of the
      experiment group from 12 patients whose TNM stage was up-regulated to stage IIIa.
      The 3-year survival rate (58.3%) of MUC1 mRNA positive group patients with occult
      micrometastasis in mediastinal lymph node was lower than the 88.0% of MUC1 mRNA
      negative group (P < 0.05). CONCLUSION: Occult micrometastasis in the mediastinal
      lymph node in NSCLC patients can be diagnosed by MUC1 mRNA expression through RT
      PCR. Poor prognosis in some pN(0) NSCLC patients may be associated with nodal
      occult micrometastasis.

PMID- 12515618
TI  - [Lung cancer risk associated with genetic polymorphism in myeloperoxidase (-463
      G/A) in a Chinese population].
AB  - OBJECTIVE: To examine the relationship between susceptibility to lung cancer
      among Chinese and genetic polymorphism at nucleotide -463 (G/A) in
      myeloperoxidase (MPO), an enzyme found in lysosomes of phagocytes and involved in
      the formation of hydroxyl radicals and activation of various smoking-related
      carcinogens. METHODS: The association of this polymorphism with lung cancer in a
      hospital-based case-control study of 314 patients and 320 age- and sex-matched
      controls was tested. The MPO genotypes were determined by polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP). RESULTS: The allele
      frequency for MPO-463A was found to be 11.0% for controls, compared with 15.0%
      for patients. Multivariate analysis showed an increased risk for overall lung
      cancer in subjects having GG genotype (OR, 1.7; 95% CI, 1.2 - 2.5), however, the
      elevated risk was limited to squamous cell carcinoma (OR, 2.4; 95% CI, 1.4 - 3.9;
      n = 177) but not to adenocarcinoma (OR, 1.3; 95% CI, 0.8 - 2.1; n = 137). In
      addition, the risky effect of the GG genotype on squamous cell carcinoma of the
      lung was evident only in the smokers and those who smoked >/= 26 pack-years (OR,
      20.5; 95% CI, 5.6 - 75.3) as compared with GA and AA genotypes (OR, 6.2; 95% CI,
      1.7 - 22.5) but not in the nonsmokers or those who smoked < 26 pack-years.
      CONCLUSION: Our data support the hypothesis that -463A polymorphism in the MPO
      gene may reduce the susceptibility to lung cancer in the Chinese.

PMID- 12515619
TI  - [Influence of thalidomide on interleukin-6 and its transmission in multiple
      myeloma patients].
AB  - OBJECTIVE: To evaluate the mechanism and influence of thalidomide on interleukin
      6 (IL-6), IL-6 receptor (IL-6R) and its transmitting chain in multiple myeloma
      patients. METHODS: Serum level of IL-6, expression of IL-6R on myeloma cells and
      IL-6R beta mRNA in multiple myeloma patients were measured by enzyme linked
      immunosorbent assay (Elisa), flow cytometry and reverse transcription polymerase
      chain reaction (RT-PCR). RESULTS: Serum level of IL-6 in multiple myeloma
      patients was 564.8 +/- 319.4 ng/L, with a positive rate on the myeloma cells of
      33.6% before oral 200 mg/d thalidomide. They were 560.3 +/- 414.8 ng/L and 31.8%
      on D14 after oral 200 mg/d thalidomide, which were not significantly different as
      compared with those before (P > 0.05). On D14, 28, 42, 56 and 84 after oral 400
      mg/d thalidomide, the serum level of IL-6 in multiple myeloma patients were 516.7
      +/- 131.9 ng/L, 426.7 +/- 180.4 ng/L, 387.9 +/- 187.4 ng/L, 350.1 +/- 85.5 ng/L
      and 212.3 +/- 92.5 mg/L, with positive rates on the myeloma cells of 28.5%,
      24.3%, 21.3%, 12.6% and 10.1%, which were all lower than those before oral 200
      mg/d thalidomide (P < 0.05 or P < 0.01). Ratios before and on D14 after oral 200
      mg/d thalidomide were 7.8 and 6.9, with no statistical significance (P > 0.05).
      Ratios on D14, 28 after oral 400 mg/d thalidomide were 5.3 and 2.7, which were
      lower than those before oral 200 mg/d thalidomide (P < 0.01). CONCLUSION:
      Reduction of serum level of IL-6 in multiple myeloma patients and decrease in IL
      6R expression on the myeloma cells and IL-6R beta mRNA occur on D14 after oral
      400 mg/d thalidomide. These changes become more obvious with time. The antitumor
      mechanism of thalidomide may be related to reduction of IL-6 serum level in
      multiple myeloma patients and decrease in IL-6R expression on the myeloma cells
      and IL-6R beta mRNA.

PMID- 12515620
TI  - [Micrometastasis distribution in liver tissue surrounding hepatocellular
      carcinoma].
AB  - OBJECTIVE: To study the micrometastasis distribution in liver tissue surrounding
      hepatocellular carcinoma (HCC), and provide reference for appropriate surgical
      safety margin. METHODS: Thirty-six patients with HCC but without clinical
      metastasis underwent hepatectomy. Their specimens showing ample surgical margin
      were made into giant sections. Tumor micrometastasis in liver tissue around the
      primary tumor were examined microscopically. In each specimen, the surrounding
      tissue was divided into proximal(p) and distal(d) areas. In either area, three
      lines of demarcation 0.5 cm, 1.0 cm, and 2.0 cm away from the margin of the
      primary tumor were designated as L(0.5), L(1.0) and L(2.0). Therefore, the
      surrounding tissue was divided into six zones - Z(p0.5), Z(p1.0), Z(p2.0) and
      Z(d0.5), Z(d1.0), Z(d2.0). The maximum micrometastasis spread distance (MMSD) and
      density (D(p0.5), D(p1.0), D(p2.0) and D(d0.5), D(d1.0), D(d2.0)) in each zone
      were analyzed after search for micrometastasis in the giant sections. RESULTS:
      72.5% (111/153) micrometastases were found in form of microscopic tumor emboli.
      Their spread distance could be up to 6.1 cm. In 66.7% (24/36) specimens,
      micrometastases were found in the surrounding tissue. In 91.7% (22/24) of them,
      the distal MMSD was less than 3 cm. The proximal MMSD was less than 1.5 cm in
      92.3% (12/13). The comparison of micrometastasis density in the different zones
      were D(d0.5) > D(d1.0) > D(d 2.0); D(p0.5) > D(p1.0) > D(p2.0); D(d1.0) >
      D(p1.0); D(d2.0) > D(p2.0) with significant differences. CONCLUSION: (1)
      Micrometastases of HCC exist mainly in form of microscopic tumor emboli, (2) The
      longer the distance from the primary focus, the lower the micrometastasis
      incidence, (3) In zones more than 0.5 cm away from the primary focus, tumor
      micrometastasis incidence is significantly lower in the proximal zones than that
      in the distal zones and (4) For HCC patients without clinical metastasis, a
      surgical margin of 3 cm wide in the distal area and 1.5 cm wide in the proximal
      area may reduce the rate of postoperative recurrence.

PMID- 12515621
TI  - [Significance of cytokeratin gene (CK-20 mRNA) expression in metastatic lymph
      nodes in colon carcinoma patients].
AB  - OBJECTIVE: To elucidate the significance of detecting cytokeratin gene (CK-20
      mRNA) expression in metastatic lymph nodes of colon carcinoma patients. METHODS:
      The expression of CK-20 mRNA was detected in 342 lymph nodes by reverse
      transcription-polymerase chain reaction (RT-PCR) in 49 colon carcinoma patients.
      Its incidence was compared with that by routine pathologic examination. RESULTS:
      The positive rates of detecting metastasis in the lymph nodes were 21.9% by RT
      PCR and 11.1% by routine pathologic examination. CONCLUSION: The detection of
      cancer metastasis in the lymph nodes in colon carcinoma is almost doubled (21.9%
      vs 11.1%) by CK-20 mRNA, which may provide a guiding significance in staging,
      treatment planning and prognosis in the prognostic estimation of colon carcinoma
      patients.

PMID- 12515622
TI  - [Expressions of beta-catenin, p53 and proliferating cell nuclear antigen in the
      carcinogenesis of colorectal adenoma].
AB  - OBJECTIVE: Research was done on the possible roles of beta-catenin, p53 and
      proliferating cell nuclear antigen (PCNA) in the carcinogenesis of colorectal
      adenoma (CRA). METHODS: beta-catenin and p53 and PCNA expressions were studied
      with immunohistochemical stain in 77 specimens of CRA together with mild
      epithelial dysplasia (CRA-MD), CRA with moderate/severe epithelial dysplasia (CRA
      D/SD) and CRA with cancerous changes (CRA-C). RESULTS: The percentage of abnormal
      expression of beta-catenin increased during the transition from CRA-MD to CRA
      D/SD to CRA-C (P < 0.01). The nuclear expressions of beta-catenin in CRA-D/SD and
      CRA-C were all significantly higher than that in CRA-MD. Expression of p53 and
      PCNA were increased from CRA-MD to CRA-D/SD to CRA-C, with the positive rates in
      these three groups of 10.3%, 43.8%, 75.0% for p53 and 17.2%, 62.5%, 87.5% for
      PCNA, respectively. 69.7% of cases with positive nuclear beta-catenin expression
      showed strong PCNA positivity which was much higher than the 36.4% of cases
      without nuclear beta-catenin expression (P < 0.05). The percentage of strong PCNA
      expression in the p53 positive cases was significant higher than that in cases
      with negative p53 expression (72.4% vs 37.5%, P < 0.05). Nuclear beta-catenin and
      p53 co-expression rates in CRA-C reached 50%. CONCLUSION: beta-catenin, p53 and
      PCNA may play important roles in the carcinogenesis of colorectal adenoma.

PMID- 12515623
TI  - [Fas and Fas-L expression in human adenocarcinoma of uterine cervix].
AB  - OBJECTIVE: To study the significance of Fas and Fas-L expression in
      adenocarcinoma of uterine cervix. METHODS: Both carcinoma tissue and their
      surrounding tissues from 36 patients with adenocarcinoma of uterine cervix,
      previously untreated either by radiation or chemotherapy, were studied for the
      expression of Fas and Fas-L by immunohistochemical stain with DNA apoptosis
      fragment detected by TUNEL. RESULTS: The TUNEL labeling index was negatively
      correlated with differentiation of adenocarcinoma of cervix. Compared to highly
      differentiated and moderately differentiated tumor, the TUNEL labeling index was
      reduced obviously in poorly differentiated adenocarcinoma (P < 0.01). Fas
      expression was detected in 31 cases (86%) while there were only 3 weakly stained
      in the normal endocervical glands around the carcinoma. The 5 unstained
      carcinomas were 3 highly differentiated and 2 moderately differentiated. The
      positively stained Fas was associated with differentiation; the stronger the
      stain, the less differentiation there was. The Fas-L expression was detected in
      all adenocarcinomas while there was only 1 weakly stained in the normal ones. No
      significant difference was found in the expression of Fas-L in carcinomas with
      different degrees of differentiation. No correlation was observed between Fas and
      Fas-L expression. CONCLUSIONS: The Fas expression is positively correlated with
      the different degrees of differentiation and Fas-L expression may be associated
      with the escape from of immunal surveillance.

PMID- 12515624
TI  - [Significance of fatty acid synthase expression in non-small cell lung cancer].
AB  - OBJECTIVE: To evaluate the expression of fatty acid synthase (FAS) in non-small
      cell lung cancer (NSCLC). METHODS: FAS was examined by immunohistochemical S-P
      technique in 175 specimens of NSCLC patients. Multiple clinical factors were
      analyzed according to their relation with expression of FAS. RESULTS: The overall
      FAS expression rate was 31.4% (55/175). The expression of FAS in the non
      adenocarcinoma patients was significantly higher than that of adenocarcinoma
      patients (38.4% vs 22.4%, P = 0.036). Higher FAS expression was also detected in
      patients who had vascular invasion or bone metastasis than those without (75.0%
      vs 29.3%, P = 0.02 and 46.9% vs 28.0%, P = 0.037). But, there was no significant
      difference between FAS and other clinical factors such as age, sex, smoking
      index, tumor size, stage, degree of differentiation, lymphatic metastasis, local
      recurrence or distant metastasis. Although there was no significant difference in
      the survival rates of FAS positive and negative patients (P = 0.066), the
      survival rate of FAS positive stage I patients was lower than that of negative
      ones (P = 0.005). CONCLUSION: Fatty acid synthase in the specimens of non-small
      cell lung cancer patients has no correlation with most clinical factors, except
      that, in early lesions, it may signify poor prognosis.

PMID- 12515625
TI  - [Spiral CT in the preoperative staging of colorectal carcinoma-radiologic
      pathologic correlation].
AB  - OBJECTIVE: To evaluate spiral CT (SCT) in the preoperative staging of colorectal
      carcinomas. METHODS: Fifty-one patients suspicious of having colorectal carcinoma
      underwent spiral CT scans performed from the dome of the diaphragm to symphysis
      pubica after cleansing enema and rectal air insufflation. Fourty-one of the 51
      patients were proved to have colorectal carcinoma by colonoscopy and/or
      pathology. The findings of SCT of 31 patients treated with surgery were compared
      with the surgical pathological examination for staging. RESULTS: The overall
      accuracy rate of SCT staging was 58.1% (18/31). For evaluation of T staging and N
      staging, the accuracy rates were 84.4% (27/32) and 61.3% (19/31). Sensitivity and
      specificity for serosal infiltration were 92.9% (26/28) and 50.0%, They were
      70.0% (14/20) and 81.8% (9/11) for lymph node involvement. CONCLUSION: SCT scan,
      playing a significant role in the preoperative staging of colorectal carcinoma,
      is useful to detect the serosal infiltration, lymph node and distant metastasis.

PMID- 12515626
TI  - [High intensity focused ultrasound alone for malignant solid tumors].
AB  - OBJECTIVE: To investigate the efficacy and side-effects of high intensity focused
      ultrasound (HIFU) in the treatment of malignant solid tumors. METHODS: Thirty
      such patients who refused surgery and or refractory to chemotherapy, were treated
      by HIFU alone, with the efficacy and side effects monitored in terms of vital
      organ signs observation, functional assay of important organs, imaging
      examinations: digital subtraction angiography (DSA), CT, MRI, single
      photoemission computed tomography (SPECT), large core needle biopsy,
      complications or metastasis. RESULTS: After HIFU therapy, the vital signs
      remained stable and the function of heart, lung, kidney and liver was also
      normal. DSA images showed that small or larger arteries were not damaged. After a
      follow-up of 10 - 38 months (23.1 months), 26 patients (87%) have been alive. The
      volume of the tumor underwent complete regression in 10 patients. Shrinkage of
      tumor volume >/= 50% was observed in 13. Eight of 13 patients were examined by
      large core needle biopsy, all showing necrosis and/or fibrosis though 3 patients
      (10%) had local recurrence. Two of these were retreated again by HIFU and the
      locally recurrent tumor became well controlled. New metastases developed in 5
      patients after HIFU therapy. Two patients suffered from peripheral nerve
      injuries, most of which have recovered during the follow-up. However, one patient
      developed skin injury. CONCLUSION: High intensity focused ultrasound alone is
      effective and safe in the treatment of malignant solid tumors.

PMID- 12515627
TI  - [Ultrasound-guided percutaneous microwave coagulation therapy for primary
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the long-term results of percutaneous microwave
      coagulation therapy (PMCT) for primary hepatocellular carcinoma. METHODS: From
      May 1994 to May 2000, 177 hepatocellular carcinoma patients with 265 nodules
      underwent PMCT with ultrasound (US) guidance. The tumor size varied from 1.5 to
      8.7 cm (median 4.12 + 1.9 cm). Follow-up examination was carried out with colour
      US, CT, MRI and AFP. 184 nodules were re-biopsied during the follow up of 5 - 74
      months (median 29 months). RESULTS: After PMCT, colour Doppler flow signals
      disappeared in 92.0% (207/225) of patients. No enhancement was observed in 88.5%
      (138/156) by CT and 88.9% (32/36) by MRI. Re-biopsy of 184 nodules showed
      complete necrosis in 92.4% (170/184). Six resected lesions showed complete tumor
      necrosis in 5 and subtotal necrosis in 1. The 1- to 5-year survival rates were
      90.1%, 76.9%, 68.3%, 64.2% and 57.8%, respectively. The survival rates of the
      well differentiated lesions were better than those of the poorly ones (P < 0.05).
      But there was not statistical significance between the moderately and the well
      differentiated ones. The new lesions development rates in 1 to 5 years were
      26.1%, 37.8%, 43.5%, 48.6% and 58.9%, respectively. However, there was no severe
      complication. CONCLUSION: Ultrasound-guided microwave coagulation is safe and
      effective for primary hepatocellular carcinoma. It can eliminate tumors less than
      5 cm in diameter.

PMID- 12515628
TI  - [Transarterial embolization for hemorrhage due to spontaneous rupture in
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the efficacy of transarterial embolization (TAE) for
      intraperitoneal hemorrhage due to spontaneous rupture in hepatocellular carcinoma
      (HCC). METHODS: Fourty-two patients with ruptured HCC were divided into 4 groups
      according to the type of their previous treatment: Group A-TAE followed by
      elective hepatectomy 15, Group B- TAE alone 11, Group C-emergency operation 6 and
      group D-medical conservative management 10. RESULTS: Celiac arteriography done
      before the present treatment showed extravasation of contrast material in 7
      (26.9%) of the 26 patients in group A and B, and hypervascular tumor was observed
      in the rest. The hemostasis success rate of group A, B and C were 100%, which
      were much higher than that of group D (40%) (P < 0.05). The in-hospital mortality
      rates of group A, B and C were 0, 3.8% and 16.7% (P > 0.05), which were much
      lower than that of group D (80%) (P < 0.01). The 1-year survival rate of group A
      (76.3%) was higher than those in groups B (47.5%) and C (43.7%) (P < 0.05). There
      was no 1-year survivor in group D. CONCLUSION: Transarterial embolization is safe
      and effective for hemorrhage due to spontaneous rupture in hepatocellular
      carcinoma. For resectable lesions, TAE is a preferential treatment to be given
      first, then followed by elective hepatectomy.

PMID- 12515629
TI  - [Preservation of laryngeal function in surgery for medial wall pyriform sinus
      cancer].
AB  - OBJECTIVE: To study the feasibility, surgical technique and results of laryngeal
      function preservation in surgical treatment for medial wall pyriform sinus
      cancer. METHODS: From 1992 to 1999, 31 patients with medial wall pyriform sinus
      cancer including stage I 1, II 4, III 14 and IV 12 lesions were treated. Partial
      resection of pyriform sinus and partial laryngectomy were performed, then, the
      remains of epiglottis and uni-pedicled sternohyoid myofascial flap were used to
      restore the defects of larynx. At last, the remaining hypopharyngeal mucosa was
      sutured to cover the wound of hypopharynx and for artificial rebuild-up. All
      patients received postoperative radiotherapy. RESULTS: The 3- and 5-year survival
      rates were 62.1% and 43.6% respectively, with 77.4% patients having laryngeal
      functions (voice, respiration and deglutition) completely restored and 32.6%
      partially restored (voice and deglutition). CONCLUSION: Conservative surgery so
      introduced is feasible for selected medial wall pyriform sinus cancer patients
      with the lesion completely resected.

PMID- 12515630
TI  - [Combination of subradical external radiation and brachytherapy plus radical
      operation in the treatment of carcinoma of uterine cervix].
AB  - OBJECTIVE: To summarize retrospectively the 5-year survival rates and long-term
      complication of stage Ib-IIIa cervical carcinoma treated by combination of
      subradical external radiation and brachytherapy plus radical operation. METHODS:
      106 patients with cervical carcinoma were all treated by radical hysterectomy and
      pelvic lymphadenectomy, of whom 78 had had preoperative radiotherapy (external
      radiation and brachytherapy), 16 combination of brachytherapy and radical
      operation, 12 adjuvant postoperative radiotherapy (external radiation and
      brachytherapy). (60)Co was used for external radiation, in which the point B dose
      was 25 - 30 Gy in preoperative radiation and 40 - 50 Gy in postoperative
      radiation. (192)Ir high-dose-rate afterloading unit was used in brachytherapy,
      with a dose of 6 - 18 Gy at point A. RESULTS: The follow up rate was 95.3%. The
      overall 5-year survival rates were 78.2% (61/78) in the preoperative radiotherapy
      group, 68.8% (11/16) in brachytherapy plus radical operation, 33.3% (4/12) in the
      postoperative radiotherapy group, showing a higher 5-year survival rate in the
      preoperative radiotherapy group than the postoperative radiotherapy group (P <
      0.05). In stage II patients, the preoperative radiotherapy group -77.6% (45/58)
      also gave a higher survival than the postoperative radiotherapy group -25.0%
      (1/4) (P < 0.05). But all the other groups gave differences of insignificance.
      The chief long-term complications were radio-proctitis and cystitis, with
      incidences of 34.6% (27/78), 31.3% (5/16), 33.3% (4/12) in the preoperative
      radiotherapy group, brachytherapy plus radical operation group and the
      postoperative radiotherapy group (P > 0.05). CONCLUSION: The overall 5-year
      survival rate of combined subradical external radiation and brachytherapy plus
      radical operation was obviously higher than that of postoperative radiotherapy
      for stage Ib-IIIa and II patients, with statistically significant differences.
      However, the incidence of long-term complications give no statistical
      significance in the preoperative radiotherapy group or brachytherapy plus the
      operation group as compared with the postoperative radiotherapy group.

PMID- 12515631
TI  - [Low-dose rate intracavitary afterloading radiotherapy for cancer of uterine
      cervix].
AB  - OBJECTIVE: To evaluate the results of Gynatron low dose rate (LDR) brachytherapy
      for cancer of uterine cervix. METHODS: From April 1980 to June 1986, 136 patients
      with uterine cervical carcinoma were given radical radiotherapy through LDR
      afterloading irradiation and (60)Co external irradiation, compared with those
      through radium and high dose rate (HDR) intracavitary therapy. RESULTS: All
      patients except 5 were followed up for 15 years with a follow-up rate of 96.3%
      (131/136). The overall 10-year survival rate was 63.5%. The 10-year survival
      rates of stage II and III patients were 83.9% and 43.2%. The frequency of
      proctitis and cystitis were 12.5% (17/136) and 9.6% (13/136). CONCLUSION:
      Gynatron LDR system has achieved good results with tolerable complications
      including proctitis and cystitis which are more often than those of radium and
      less so than those of HDR.

PMID- 12515632
TI  - [Cause of failure and false negative result in sentinel lymph node biopsy through
      vital blue injection in breast carcinoma].
AB  - OBJECTIVE: To investigate the cause of sentinel lymph node biopsy failure and
      false negative result in vital blue injection for breast cancer. METHODS: Eight
      four female breast cancer patients were injected with vital blue to find the
      sentinel lymph nodes during operation. All patients were treated by the
      traditional radical or modified radical mastectomy with axillary dissection after
      sentinel node biopsy. All sentinel nodes, axillary lymph nodes and dissected
      specimens were submitted separately to pathological examination. RESULTS:
      Sentinel node was not identified at the time of operation in 11 patients, giving
      a failure rate of 13.1%. In 73 patients in whom sentinel nodes were identified,
      32 (43.8%) revealed cancer invasion. Postoperative axillary node pathology showed
      cancer metastasis in all of them. Two patients who showed uninvaded sentinel
      nodes were demonstrated to have axillary node metastasis. These were the two
      false negative patients. Therefore, the prediction of axillary metastasis by the
      sentinel node biopsy showed a sensitivity of 90.4%, a specificity of 100% and a
      false negative rate of 2.7%. CONCLUSION: Failure in identifying the sentinel
      nodes in vital blue injection is related to the degree of mastering the technique
      and the method of injection. The cause of false negative result is due to an
      extensive primary tumor and the variation in the position of the sentinel lymph
      nodes.

PMID- 12515633
TI  - [Surgical treatment for lung cancer patients with poor pulmonary function].
AB  - OBJECTIVE: To summarize surgical treatment of lung cancer patients with poor
      pulmonary function. METHODS: From 1991 to 1999, 181 lung cancer patients with
      poor pulmonary function underwent operation. The correlation between the results
      of preoperative pulmonary functional tests and the postoperative cardiopulmonary
      complications was analyzed by Chi-square test (chi(2)). RESULTS: In 181 patients,
      pneumonectomy was done in 43, lobectomy in 118, partial lung resection in 16 and
      exploration in 4. The postoperative complication and mortality rates of the
      resection group were 42.3% (75/177) and 7.9% (14/177). The cardiopulmonary
      complication rates were 25.6%, 48.3%, 31.3% in pneumonectomy, lobectomy and
      partial lung resection. The morbidity and mortality rates of 8 patients who
      received preoperative chemotherapy and/or radiotherapy were 75.0% and 37.5%. The
      morbidity and mortality rates of 12 patients who had had a previous history of
      thoracotomy were 66.7% and 33.3%. In the present series, the 1-, 3- and 5-year
      survival rates were 71.1%, 42.2% and 31.1%. The 5-year survival rates of patients
      with stage I, II and III lesions were 55.0%, 25.0% and 0. CONCLUSION:
      Preoperative spirometry is an important evaluation test for lung cancer patients
      with poor pulmonary function. It should be evaluated in combination with other
      pulmonary function tests such as CO(2) diffusion and cardiopulmonary excise
      tests, etc whenever possible. Patients with a history of thoracotomy,
      chemotherapy and radiotherapy should be carefully evaluated before operation to
      avoid high morbidity and mortality. Stage I and II lung cancer patients with poor
      pulmonary function can undergo operation if they have been well managed
      preoperatively and well taken care of with nursing care perioperatively.

PMID- 12515634
TI  - [Evaluation of two different regimens as neoadjuvant chemotherapy for breast
      cancer].
AB  - OBJECTIVE: To compare the efficacy and toxicity of two different regimens as
      neoadjuvant chemotherapy for breast cancer. METHODS: Forty-eight patients with
      stage II, III breast cancer as proved by cytology biopsy, were treated with
      either 5-Fu, epirubicin, cyclophosphamide (FEC) or epirubicin, paclitaxel (ET)
      regimens for 2 cycles every 3 - 4 weeks. Clinical responses in the breast and
      lymph nodes were assessed after 2 cycles of neoadjuvant chemotherapy. Patients in
      FEC arm received combination of 5-fluorouracil (5-Fu) 500 mg/m(2) by 4-hour
      continuous infusion on D1 and D8, epirubicin (EPI) 50 mg/m(2) by intravenous
      injection on D1, and cyclophosphamide (CTX) 500 mg/m(2) by intravenous injection
      on D1 and D8. Patients assigned to the ET arm received EPI 60 mg/m(2) by
      intravenous injection on D1, paclitaxel (TAX) 150 mg/m(2) by 3-hour continuous
      infusion on D2. All patients were treated by operation 2 weeks later and
      radiotherapy was added to some. RESULTS: For primary tumor in the breast, the
      overall response rate (RR) was 50.0% (12/24) in FEC arm and 79.2% (19/24) in ET
      arm. One patient showed clinical complete response (cCR), 11 partial response
      (PR), 12 no change (NC) after the FEC therapy, while 1 patient showed CR, 18 PR,
      5 NC after ET therapy. There was no pathologic complete response or progressive
      disease, though a higher proportion of RR was observed in stage II than stage III
      patients in these two groups. Clinically palpable axillary lymph nodes which had
      been found in all 48 patients before 2 cycles of treatment, 50.0% (12/24) in the
      FEC patients and 66.7% (16/24) in the ET patients became in-palpable. The major
      toxicity, including leukopenia, gastroenteric reactions, were similar in both
      groups, but alopecia was more severe and arthralgia, myalgia, neurotoxicity and
      flushing of face were the unique features of the ET regimen. CONCLUSION:
      Neoadjuvant chemotherapy with two different regimens were effective to the
      primary tumor and axillary metastatic lymph nodes of breast cancer, and the side
      effects were tolerable. Higher efficacy and more side effects are observed in ET
      than in FEC regimen.

PMID- 12515635
TI  - [The influence of burn sera on the nuclear translocation of endothelial NF-kappaB
      p50 and p65].
AB  - OBJECTIVE: To investigate the effects of burn sera on the nuclear translocation
      of endothelial NF-kappaB heterodimers p50/p65 and on the degradation of
      inhibiting kappaB (IkappaBalpha), in order to explore the role of burn sera on
      activation of the endothelium. METHODS: Cultured human umbilical vein endothelial
      cells (HUVECs) (ECV-304 strain) were employed as the target cells. The cells were
      stimulated by sera from healthy volunteers and from burn patients and burn sera
      together with PDTC (pyrrolidine dithiocarbarnate). The normal cultured cells were
      taken as the control. The nuclear translocation of endothelial p50/p65 at 30, 60,
      120 and 480 mins after the stimulation was observed with laser confocal
      microscopy, and the endothelial IkappaBalpha protein degradation at 30, 60, 90
      and 120 mins after the stimulation was determined by Western blotting. RESULTS:
      When compared to that in control group, the nuclear translocation of p50/p65 took
      place 30 mins after the endothelial cells were stimulated by burn sera, and it
      reached the summit at 30 - 60 mins, but recovered to pre-stimulation state at
      2hrs. In addition, IkBalpha degradation occurred 30 mins after the cells were
      stimulated by burn sera (P < 0.01) and peaking at 45 - 60 mins after the
      stimulation and recovered at 2hrs after the stimulation. The nuclear
      translocation of endothelial p50/p65 and IkBalpha degradation at 30 and 60 mins
      after the stimulation by burn sera could be effectively inhibited by PDTC.
      CONCLUSION: Burn sera might induce the nuclear translocation of endothelial NF
      kappaB p50/p65 and IkappaBalpha degradation and activate NF-kappaB, which
      ultimately lead to the secretion of cytokines from the endothelium.

PMID- 12515636
TI  - [An experimental study on the influence of inhibition of postburn stress on
      inflammatory reaction in severely scalded rats].
AB  - OBJECTIVE: To investigate the influence of hibernation drugs on postburn stress
      and inflammatory reaction in severely scalded rats. METHODS: Sprague-Dawley rats
      inflicted with 30% TBSA deep partial thickness scalding were employed as the
      model. The rats were divided into A (scalding with immediate resuscitation), B
      (scalding with immediate resuscitation and lytic cocktail), C (scalding with
      delayed resuscitation), D (scalding with delayed resuscitation and lytic
      cocktail) and E (sham injury) groups. The rat plasma levels of NE
      (norepinephrine), E (epinephrine) and DA (dopamine) were determined by HPLC (high
      performance liquid chromatography) at 3, 6, 12, 24 and 48 postburn hours (PBHs),
      and the plasma IL-1alpha and PGE(2) levels were detected by ELISA (enzyme-linked
      immunosorbent assay) and RIA (radioimmunoassay) methods. The NF-kappaB activity
      in PBMCs (peripheral blood mononuclear cells) was determined by laser scanning
      confocal microscope. RESULTS: The plasma NE and E levels reached summit at 6 PBH,
      while those in B group were lowest. But the plasma DA level was similar among all
      groups at all time points. The plasma IL-1alpha and PGE(2) levels increased
      continuously, however, the levels were were lower in B than A groups at the same
      time points, and also that of D were lower than C groups. At the same time
      points, the levels in B group were lower than those in D group. The NF-kappaB was
      located in the cytoplasma of PBMCs in E group and in the nucleus in A group at 6
      PBH. Furthermore, the NF-kappaB was concentrated more in the cytoplasm than that
      in the nucleus in B group, while it was more concentrated in the nucleus in C and
      D groups. CONCLUSION: The secretion of stress hormones could be attenuated by
      hibernation drugs. The plasma cytokine levels and the nuclear translocation of NF
      kappaB in PBMCs could also be modulated by the drugs.

PMID- 12515637
TI  - [The relationship between apoptosis of the cardiac myocytes and myocardial
      dysfunction in severely scalded rats].
AB  - OBJECTIVE: To investigate relationship between apoptosis of the cardiac myocytes
      and myocardial dysfunction in severely scalded rats. METHODS: Wistar rats
      inflicted by 40% TBSA III degree scalding were employed as the model. The
      myocardial tissue was obtained from the left ventricle at different postburn time
      points. Apoptosis was determined by the determination of myocardial tissue
      Caspase-3 activity and TUNEL staining (terminal deoxynucleotidyl transferase
      (TdT)-mediated dUTP-biotin nick end labeling). The LVSP (left ventricular
      systolic pressure), LVEDP (left ventricular end-diastolic pressure) and +dp/dtmax
      (the rate of the rise of left ventricular pressure) and -dp/dtmax (the rate of
      the fall of left ventricular pressure) were all monitored by four-channel
      physiological recorder. In addition, myocardial activities of MPO and SOD were
      detected. RESULTS: The TUNEL staining of rat myocardial cells was positive at 6
      postburn hour (PBH) and reached top level at 12 PBH. The change in Caspase-3
      activity was earlier than that of apoptotic morphology and reached peak values at
      3 and 6 PBHs. The left ventricular function (systolic and diastolic function) was
      significantly impaired after the scalding and dropped to the lowest levels at 12
      PBHs. The increase in myocardial tissue MPO activity was accompanied by the
      decrease in SOD activity. CONCLUSION: Myocardial cellular apoptosis was one of
      the reasons of postburn myocardial injury in scalded rats. Caspase protease
      cascade pathway might be involved in the process of apoptosis, which suggested
      that the initiation of apoptosis was closely related to the infiltration of
      neutrophils and to the release of large amounts of oxygen free radicals in
      myocardial tissue.

PMID- 12515638
TI  - [Study on the intra- and extra-hepatocyte distribution of sodium ions in scalded
      rats during early postburn stage].
AB  - OBJECTIVE: To investigate the characteristics of the intra- and extra-hepatocyte
      sodium ions distribution in scalded rats during early postburn stage,with the aim
      of improving burn shock resuscitation regime and the resuscitation effects.
      METHODS: Adult Sprague-Dawley rats were randomly divided into sham scalding (C, n
      = 12) and scalding (S, n = 7) groups. The rats in S group were subjected to 40%
      TBSA III degree scalding on the back and were catheterized via jugular vein for
      fluid resuscitation. The rats in C group were catheterized via jugular vein
      without fluid infusion and were sham scalded by warm water in temperature of 37
      degrees. The changes in the intra- and extra-hepatocyte sodium ion contents were
      determined in vivo by (23)Na-magnetic resonance spectrum technology, while the
      existing state of the intra- and extra-hepatocyte sodium ion was determined by
      detecting (23)Na-magnetic resonance horizontal delaying time (T(2)). RESULTS: The
      extra-hepatocyte sodium content in S group at 24 postburn hours (PBHs) was 17%
      less than that in C group. In addition, the T(2f) (fast T(2)) in S group remained
      stable but maintained a higher ratio during the observation time. This suggested
      that the sodium binding sites in extra-hepatocyte matrix increased relatively and
      that intra-hepatocyte sodium content increased by 57%. But the T(2) and the fast
      and slow parts of the T(2) kept stable, which implied that intra-hepatocyte
      catabolizing products were increased. This led to an increase in the sodium ion
      binding sites within intra-hepatocyte matrix in proportion to the sodium ion
      content. CONCLUSION: During early postburn stage, the extra-hepatocyte sodium in
      a remote organ such as the liver exhibited relative deficiency due to its ingress
      into hepatocyte cytoplasm and to the increase of sodium combining sites.

PMID- 12515639
TI  - [The significance of the expression of endothelial ICAM-1 induced by LPS].
AB  - OBJECTIVE: To investigate the significance of the expression pattern and its
      signal modulating mechanism of endothelial ICAM-1 induced by LPS. METHODS: (1)
      The expression pattern of the ICAM-1 was observed at mRNA level in cultured human
      umbilical vascular endothelial cells (HUVECs) strain ECV-304 after being
      stimulated by different LPS concentrations at different time points. (2) The
      modulating effects of different signal pathways on the ICAM-1 expression of the
      HUVECs were observed at mRNA and protein levels under the stimulation of LPS
      after the cells were primed by signal pathway blocking agents for 30 mins.
      RESULTS: (1) The ICAM-1 mRNA expression could be induced by LPS (100 pg/ml) for 6
      hours, and the expression was enhanced along with the increase of LPS
      concentration. The expression peaked when LPS was at concentrations of 100
      approximately 1 000 ng/ml. Temporally, the mRNA expression reached the top level
      at 6 approximately 8 hours and remained high 12 hours after the stimulation. (2)
      The expressions of ICAM-1 mRNA and protein could be significantly inhibited by
      PSI, the NF-kappaB inhibitor. Moreover, the expression of ICAM-1 could all be
      partially inhibited at mRNA and protein levels by PD98059, the ERK1/2MAPK
      inhibitor, as well as SB203580, the p38MAPK inhibitor. CONCLUSION: The ICAM-1
      mRNA expression of HUVECs could be induced by LPS in both dose and time dependent
      manner. NF-kappaB might be the major signal pathway of modulating ICAM-1
      expression, and p38 and ERK1/2 could possibly be signal pathways of minor
      importance.

PMID- 12515640
TI  - [The role of Kupffer cells on the postburn production of TNFalpha, IL-1beta and
      IL-6 in severely scalded rats].
AB  - OBJECTIVE: To observe the role of Kupffer cells in the postburn production of
      TNFalpha, IL-1beta and IL-6 in severely scalded rats. METHODS: (1) The production
      of TNFalpha, IL-1beta and IL-6 from rat Kupffer cells stimulated by burn serum
      was observed. (2) The postburn change in the expression of cytokine mRNA from rat
      Kupffer cells was monitored. (3) The change in the plasma cytokine contents in
      scalded rats was determined after the application of gadolinium chloride, a
      specific inhibitor of Kupffer cells. RESULTS: Kupffer cells could be stimulated
      by burn serum to release cytokines TNFalpha, IL-1beta and IL-6. The mRNA
      expression of TNFalpha, IL-1beta and IL-6 from rat Kupffer cells increased
      significantly after injury. But the postburn plasma levels of TNFalpha, IL-1beta
      and IL-6 decreased obviously to 34.71%, 36.99% and 33.7% of those in scalding
      group, respectively, after the Kupffer cell activity was inhibited. CONCLUSION:
      The plasma cytokines, i.e. TNFalpha, IL-1beta and IL-6, were primarily produced
      from Kupffer cells after injury in scalded rats, initiated by TNFalpha, IL-1beta
      and IL-6 mRNA transcription.

PMID- 12515641
TI  - [The isolation of Pseudomonas aeruginosa from burn wound and the analysis of its
      antibiotic resistant spectrum].
AB  - OBJECTIVE: To investigate the change in the antibiotic resistant spectrum of
      Pseudomonas aeruginosa (PA) isolated from burn wounds and the production of
      inducible beta-lactamase. METHODS: VITEK-AMS system (total automatic bacterial
      identification and drug sensitivity system) and E-test concentration gradient
      were employed to perform bacterial identification and antibiotic sensitivity
      tests. K-B method was applied to detect inducible enzyme. RESULTS: The resistance
      of PA to Cephalosporin and Imipenem was increased in the past 4 years from June
      of 1996 to June of 2000. Whereas the resistance to Cefoperazone/Sulbactam was
      least. There was an obvious difference of the resistance of PA to antibiotics
      during the 4 years (P < 0.05). The resistant rate to Imipenem ranged from 20% to
      40%. PA was able to produce inducible enzymes among 120 strains of wild type of
      PA occupying 72.5% with Imipenam as the inducing agent. CONCLUSION: The analysis
      of the antibiotic resistance of PA and the detection of inducible enzymes could
      be monitored from time to time and helpful in the correction of the use of
      antibiotics. Constant monitoring of antibiotic resistance might be beneficial to
      the prevention of outbreak of epidemics of PA infection in a burn unit.

PMID- 12515642
TI  - [Clinical evaluation of the effects of rhGH on the management of severely burned
      patients].
AB  - OBJECTIVE: To investigate the effectiveness and the safety of clinical use of
      rhGH in the management of severe burn patients. METHODS: Two hundred burn
      patients aged 20 - 25 yrs with TBSA from 20% to 50% and admitted within 5
      postburn days (PBD) were enrolled in this study. The patients were divided into
      operation and non-operation groups. Furthermore, each group was randomly divided
      into control (N), treatment with rhGH in dosage 0.2 IU/Kg/d (A) and treatment
      with rhGH in dosage 0.4 IU/kg/d (B) groups. The general data, the metabolism of
      protein and glucose, the immune function, the urine biochemistry, the wound
      healing rate and hospital stay days recorded and compared among all groups.
      RESULTS: Plasma protein was increased, the immune function recovered early, the
      wound healing time was shortened obviously, the wound healing rate was increased
      evidently and the hospital stay days were decreased significantly in the
      treatment groups (A and B groups) compared with the N group. The body weight of
      burn patients remained unchanged in N group. Nevertheless, the plasma levels of
      glucose and insulin were increased and the urine output of potassium, sodium and
      chloride decreased in N group compared with those in A and B groups. Moreover,
      the levels of all these indices in B group were higher than those in A group,
      whereas side effects were more common in B group than in A group. In addition,
      the incidence of adverse reaction was higher in operation group than that in non
      operation group. CONCLUSION: rhGH could effectively promote protein synthesis,
      enhance systemic immune function, accelerate wound healing and shorten hospital
      stay days in severely burned patients. But attention should be paid to
      appropriate dosage and duration of use.

PMID- 12515643
TI  - [Comparative study of the image observation of earlypostburn brain edema in
      severely burned dogs].
AB  - OBJECTIVE: To explore the diagnostic value of MRI and SPECT in early postburn
      brain edema in severely burned dogs. METHODS: Twenty-six mongrel dogs were
      randomized into control (n = 6) and burned groups in which every 5 dogs were
      allotted to each of following time points: 6, 12, 18 and 24 postburn hours
      (PBHs). The dogs in burn groups were inflicted with 50% TBSA of III degree skin
      burn and were infused with 5% glucose solution after 6 PBHs, so that severe early
      postburn brain edema was produced. MRI and SPECT were employed to observe
      dynamically the brain of dogs in all groups. The results were collected and
      compared with one another. RESULTS: The results indicated that with MRI brain
      morphological change of early brain edema could be shown as early as within 12
      PBH and diffuse brain edema became more obvious with elapse of time. The changes
      might be difficult to be found by MRI when T(1)WISIR decreased below 10%. T(2)WI
      SIR increased by 8.29% at 24 PBH with blurred demarcation between the brain gray
      and white matters. There was diffused and progressive nuclide ((99)TCm-ECD)
      concentration in the brain tissue as shown by SPECT at 6 PBH. The radio-nuclide
      taking ratio increased significantly after 12 PBH, especially at 24 PBH (P <
      0.01) when compared with that before burn. CONCLUSION: Combined application of
      MRI and SPECT could evidently increase sensitivity and specificity in the
      diagnosis of early postburn brain edema.

PMID- 12515644
TI  - [An observation of the morphology and the degradation of hypertrophic scar
      collagen].
AB  - OBJECTIVE: To explore the role of collagen degradation and scar morphology and
      structure in the formation of hypertrophic scar. METHODS: SDS-PAGE (sodium
      dodecyl sulfate polyacrylamide gel electrophoresis) plus collagen substrate
      electrophoresis, amino acid analysis and compound staining were employed to
      observe the collagenase activity within hypertrophic scar, collagen degradation
      and the tissue morphology of the scar. RESULTS: There exhibited deranged collagen
      fibres within hypertrophic scar, and large amounts of acid mucopolysaccharide
      closely surrounded the collagen fibres. All these led to an obvious decrease in
      collagenase activity and reduction of collagen degradation. CONCLUSION: The
      decrease of collagen degradation and the formation of hypertrophic scar might be
      closely related to the decrease in collagenase activity and the inhibiting
      activity of acid mucopolysaccharide on collagenase.

PMID- 12515645
TI  - [The influence of Matrine on apoptosis of fibroblasts and the expression of
      apoptotic modulation related protein in hypertrophic scar of rabbit ear].
AB  - OBJECTIVE: To investigate the effects of Matrine on apoptosis of fibroblasts and
      the expression of apoptotic modulation related protein in the hypertrophic scar.
      METHODS: Hypertrophic scar was produced on the ear of 24 New Zealand white
      rabbits, which were employed as the model, and were randomly and equally divided
      into control (CC) and Matrine (M) groups (12 in each group). Matrine (50 g/L) was
      injected into the ear scar in M group and with normal saline in C group once
      every four days. At 2, 4, 6, 8 and 12 weeks after the injection, the apoptotic
      fibroblast count in the scar was determined by TUNEL method, and the expressions
      of apoptosis related modulation proteins p53, bcl-2, bax were detected by
      immunohistochemistry method. RESULTS: The apoptotic fibroblast count was much
      larger in M group than that in C group at all test time points (P < 0.05).
      Furthermore, the bax expression was increased and that of p53 and bcl-2 was
      decreased significantly in M group. In adding, the scar became flat in M group.
      CONCLUSION: Matrine might obviously enhance the fibroblast apoptosis in rabbit
      ear hypertrophic scar, and up-regulate the expression of apoptosis related
      modulation protein bax and down-regulate the expression of p53 and Bcl-2.

PMID- 12515646
TI  - [The significance of postburn changes in plasma levels of ICAM-1, IL-10 and
      TNFalpha during early postburn stage in burn patients].
AB  - OBJECTIVE: To observe the postburn changes in the plasma levels of ICAM-1, IL-10
      and TNFalpha during early postburn stage. METHODS: Nineteen burn patients were
      enrolled in the study. The plasma levels of the above 3 kinds of factors were
      determined with ELISA in the peripheral plasma of the patients, plasma samples
      from 11 healthy volunteers were taken as the control. RESULTS: The plasma levels
      of ICAM-1, IL-10 and TNFalpha increased obviously postburn, especially in those
      patients who were complicated with hypovolumic shock, sepsis and MODS (P < 0.05 -
      0.01). CONCLUSION: The monitoring of the postburn changes in plasma levels of
      ICAM-1, IL-10 and TNFalpha might be helpful in the forecast of postburn sepsis
      and the development of MODS.

PMID- 12515647
TI  - [Correlative analysis of the psychological disorder with ability to resume work
      in burn patients].
AB  - OBJECTIVE: To analyze the influencing factors of the psychological disorder in
      burn patients and its correlation with the ability to resume work. METHODS: Five
      hundred and sixty burn patients aged 7 approximately 76 years old were enrolled
      in the study. The patients' psychological disorder was evaluated by self-rating
      anxiety scale (SAS), self-rating depression scale (SDS), and symptom check list
      90 (SCL-90). Global assessment scale (GAS) was employed to detect the severity of
      the psychological disorder and the social function during 1 month to 2 years of
      the convalescent stage of burn patients. Discharged burn patients were followed
      up by questionnaire and telephone for their ability to resume work. RESULTS:
      Anxiety and depression in patients with severe burn or facial burn occurred
      earlier and severer and the patients worried about the possibility to resume
      their work, the maintainance of family relation, and the ability to join the
      society, All these problems aggravated their psychological disorder. After
      psychotherapy, the disorders were obviously alleviated (P < 0.05). CONCLUSION:
      Severe psychological disorders might delay the time of patients'ability to resume
      their previous work.

PMID- 12515648
TI  - [The application of tourniquet in burn patients during tangential excision on the
      extremities].
AB  - OBJECTIVE: To investigate the application of tourniquet in burn patients during
      tangential excision on the extremities. METHODS: Seventy - nine burn patients who
      were arranged to receive tangential excision and skin grafting on the extremities
      were randomly divided into A and B groups. The patients in A group (n = 41)
      underwent the operation with the tourniquet applied continuously throughout the
      operation, while those in B group (n = 38), only with tourniquet applied during
      tangential excision. The amounts of blood loss and blood transfusion, the
      operation time and the take rate of grafted skin and the incidence of
      complications were investigated and recorded. RESULTS: The amounts of blood loss
      and blood transfusion during operation in A group were 42% and 50% less than
      those in B group, respectively (P < 0.001). Moreover, the operation time on the
      upper and lower extremities in A group was much shorter (for 41% and 37%,
      respectively) than those in B group (P < 0.001). In addition, there was no
      difference of the take rate of skin graft and the incidence of subcutaneous
      hematoma between the two groups (P > 0.05). CONCLUSION: Continuous tourniquet
      application during tangential excision on the extremities in burn patients was
      proved to be effective in reducing operational blood loss, blood transfusion and
      in shortening operation time.

PMID- 12515649
TI  - [A multicenter clinical trial of piperacillin/tazobactam in burn infection].
AB  - OBJECTIVE: To evaluate the efficacy of piperacillin/tazobactam in the management
      of burn infection. METHODS: Sixty-three burn patients were enrolled in the study
      with burn sepsis or burn area more than 50%TBSA or full skin loss more than 30%
      TBSA. The administration regime of the antibiotics was 4.5 g intravenously
      administered every 8 hours in the treatment of burn sepsis or in the prophylactic
      management. The effectiveness was identified when the septic symptoms disappeared
      or focal infection did not develop into sepsis. RESULTS: The overall clinical
      efficacy was 90.4%, and success in sepsis (control) was 75%. Furthermore, 95.7%
      of the focal infection was prevented from developing into systemic infection. The
      bacterial clearance rates were 71.4% and 51.4% in treatment and prophylaxis
      groups, respectively. CONCLUSION: Piperacillin/taxobactam was effective in the
      treatment and/or prophylaxis of burn sepsis caused by bacteria susceptible to it,
      so it could be applied empirically.

PMID- 12515650
TI  - [A preliminary in vitro study on the activation of polymorphonuclear cells and
      vascular endothelial cells co-cultured with and stimulated by
      lipopolysaccharide].
AB  - OBJECTIVE: To explore the activation of polymorphonuclear cells (PMNs) and
      vascular endothelial cells co-cultured with and stimulated by lipopolysaccharide.
      METHODS: PMNs in concentration of 2 x 10(6)/ml isolated from healthy volunteers
      by Percoll gradient were added to monolayer of ECV-304 cells grown to confluency,
      then different groups were prepared according to final concentration of
      lipopolysaccharide. The morphological change was observed under invert
      microscope. The changes in TNFalpha and IL-6 levels of the supernatant of the
      cultured cells were determined at 4, 8, 12 and 24 hours after culturation.
      RESULTS: The TNFalpha production of cultured pure ECV-304 exhibited no remarkable
      change when stimulated by different concentrations of LPS. But the TNFalpha
      production of the ECV-304 increased significantly when co-cultured with PMNs at 4
      hr and stimulated by LPS in concentration of 10 micro g/ml, and increased at 8
      hours and lasted up to 24 hours of culturation in higher levels (P < 0.05). The
      IL-6 production of cultured pure ECV-304 increased obviously along with the
      increase of LPS concentration, and it showed no change when PMNs co-cultured with
      ECV-304. While the IL-6 level in the supernatant of co-cultured ECV-304 with PMNs
      increased sharply when stimulated by both low (100 ng/ml) and high (1 micro g/ml)
      concentrations of LPS and maintained at high levels up to 24 hours of
      culturation. The higher the concentration of LPS was, the quicker the IL-6 level
      increased. CONCLUSION: Co-cultured PMNs and endothelial cells could be activated
      and activation state could be maitained by low concentrations of LPS.

PMID- 12515651
TI  - [An exploration of the preventive effects on lanthanum chloride on enteral
      bacterial translocation in scalded rats].
AB  - OBJECTIVE: To explore the preventive effect of lanthanum chloride on enteral
      bacterial translocation in scalded rats. METHODS: Ninety Sprague-Dawley (SD) rats
      were employed in the study and randomly divided into three groups, i.e. normal
      control (A), burn control (B) and treatment (C) groups. Plasmid PUC19 labelled by
      JM109 was transfected to Escherichia coli (E. coli), so that restriction
      endonuclease finger - print image spectrum analysis could be applied to the
      tracing and quantification of the translocation of E. coli from intestine to
      mesenteric lymph nodes (MLNs) and blood. The intestinal tissue contents of
      endotoxin (ET), nitric oxide (NO), nitric oxide synthase (NOS), malondialdehyde
      (MDA) and superoxide dismutase (SOD) were determined. RESULTS: It was identified
      that the bacteria in MLNs and blood exhibited the same gene map with those from
      gastric gavage in B and C groups. But the bacterial quantity in MLNs in C group
      on 3 postburn day (PBD) was much lower than that in B group (P < 0.05). The
      intestinal MDA content in C group on 1 and 3 PBDs was obviously higher than that
      in B group (P < 0.05). CONCLUSION: Bacteria (E. coli) could be translocated from
      gut to MLNs and blood, which could be evidently alleviated by lanthanum chloride
      by means of its bactericidal property, inhibition of NOS activity, so that NO
      production decreased, and its ability to increase SOD activity leading to less
      production of MDA.

PMID- 12515652
TI  - [The protective effects and its underlying mechanism of 2,4-diamino-6-hydroxy
      pyrimidine on postburn Staphylococcus aureus sepsis in rats].
AB  - OBJECTIVE: To investigate the protective effect and its underlying mechanism of
      2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP-cyclohydrolase I
      (GTP-CHI), on postburn Staphylococcus aureus (S. aureus) sepsis in rats. METHODS:
      Fifty-six Wistar rats were randomly divided into four groups, i.e. normal
      control, scalding control, postburn sepsis group and DAHP treatment group. Tissue
      samples from liver, kidneys, lungs and heart were aseptically taken, and in which
      the GTP-CHI and inducible nitric oxide synthase (iNOS) contents and the mRNA
      expression of tumor necrosis factor-alpha (TNFalpha) were determined.
      Furthermore, biopterin (BH(4)) and nitric oxide (NO) levels in these tissue were
      also measured. RESULTS: After the scalding injury followed by bacterial
      challenge, the GTP-CHI gene expression and biopterin levels were significantly
      increased in all tissue sampled, and so were iNOS mRNA expression and NO (P <
      0.01), especially in liver and lungs. The expressions of GTP-CHI mRNA and iNOS
      mRNA and the production of BH(4) and NO in all tissue were evidently inhibited by
      the pretreatment with DAHP (P < 0.05 approximately 0.01). At the same time, the
      TNFalpha expression was also obviously decreased. In addition, The mortality at 6
      hr in rats of DAHP treatment group was decreased. CONCLUSION: The prognosis of
      the scalding rats complicated by sepsis caused by G(+) bacteria could be improved
      by DAHP pretreatment, which might be related to the inhibition of the production
      of BH(4) and NO by DAHP.

PMID- 12515653
TI  - [The change in CD14 mRNA expression in rats with scald injury and Staphylococcus
      aureus challenge].
AB  - OBJECTIVE: To investigate the potential role and changes in CD14 in postburn
      Staphylococcus aureus sepsis. METHODS: Wistar rats were subjected to a 20% total
      body surface area (TBSA) full-thickness thermal injury and followed by
      Staphylococcus aureus challenge. Plasma and tissue samples from liver, kidneys,
      lungs and heart were collected to determine endotoxin (lipopolysaccharide, LPS)
      levels and CD14 mRNA expression. RESULTS: It was found that after thermal injury
      combined with Staphylococcus aureus sepsis, LPS levels in various tissues were
      markedly increased, peaking at 2 approximately 6 h (P < 0.05), then returned to
      baseline at 24 h. Plasma LPS level was also increased significantly at 2hrs after
      Staphylococcus aureus challenge compared with that in normal control animals
      (0.3056 EU/ml vs. 0.1250 EU/ml, P < 0.05). In addition, the intestinal diamine
      oxidase (DAO) activity decreased (P < 0.05). This indicated that the integrity of
      intestinal mucosa was damaged. Meanwhile, tissue CD14 mRNA expressions were up
      regulated in all tissues (P < 0.05), especially in lungs. CONCLUSION: These data
      suggested that gut-originated LPS translocation and CD14 mRNA expression could be
      induced by thermal injury with Staphylococcus aureus sepsis. The up-regulation of
      CD14 gene expression might be associated with the local endotoxin activation
      secondary to postburn sepsis.

PMID- 12515654
TI  - [An experimental study of the LPS release from gram-negative bacteria induced by
      antibiotics (Part two)].
AB  - OBJECTIVE: To explore the effects of different beta-lactam antibiotics on the
      inducing of LPS release from gram-negative bacteria and on the protection of
      infected animals. METHODS: Wistar rats were employed as the model and were
      inflicted by 30% TBSA III degree scalding and sepsis caused by PA103. The rats
      were randomly divided into 3 groups, i.e. simple antibiotic treatment group (A),
      treatment after sensitization with galactosamine (GalN) group (G) and treatment
      after blocking with carrageenan (CGN) group (C). The rats were injected intra
      peritoneally with imipenem (IMP, 5 mg) and ceftazidime (CTZ, 10 mg) for single
      time, respectively. Same amount of aseptic normal saline was injected in the
      control group, and GalN (50 mg) was added in G and CGN (1 mg) in C groups. The
      blood bacterial concentration and plasma LPS levels were determined at different
      time points after the treatment by antibiotics. The mortality was observed in G
      and C groups at 10 days after treatment. RESULTS: The blood bacterial amount
      could be decreased by both IMP and CTZ evidently. Large amounts of LPS released
      from PA103 could be induced by IMP and CTZ during their bactericidal process. But
      the plasma LPS level in rats treated by CTZ was markedly higher than that by IMP
      (P < 0.05 approximately 0.01). The mortality in G group treated by CTZ was much
      higher than that by IMP (P < 0.05). Nevertheless, the mortality in C groups was
      the same no matter CTZ or IMP was applied (P < 0.05). CONCLUSION: There was no
      difference of the bactericidal power between IMP and CTZ. But CTZ was more
      powerful in inducing LPS release from bacteria than IMP. It was implied by the
      difference between these two antibiotics that IMP might be better choice in
      clinical application for burn infection due to its lower potential of inducing
      LPS release from the bacteria.

PMID- 12515655
TI  - [The study on the role of modeling peptides derived from
      bactericidal/permeability increasing protein on the endotoxin neutralization].
AB  - OBJECTIVE: To observe the role of four modeling peptides (10342, 10343, 10344,
      10345) derived from bactericidal/permeability increasing protein (BPI) in
      neutralizing endotoxin (LPS) in vitro and in vivo. METHODS: Quantitative limulus
      amoebocyte lysate assay was employed to evaluate the capacity of BPI peptides in
      neutralizing endotoxin in vitro. The protective capacity of the peptides was
      observed in mice challenged with endotoxin by intravenous administration via the
      tail vein. The influence of the peptides on serum TNFalpha and IL-6 levels in
      rats with endotoxemia were also observed. RESULTS: All of the four peptides
      possessed endotoxin-neutralizing capacity which was strengthened along with the
      increase in their concentration. Among the peptides, 10342 is the strongest one.
      All of the peptides had strong power to protect mice from endotoxin with 90%
      protective rate. In the rats with endotoxemia, the four peptides could reduce the
      levels of serum TNFalpha and IL-6 significantly at different time-points.
      CONCLUSION: Four BPI modeling peptides possessed not only endotoxin-neutralizing
      capacity in vitro, but also potential protective capacity in animals challenged
      with endotoxin.

PMID- 12515656
TI  - [An experimental investigation of deep burn by constant low heat].
AB  - OBJECTIVE: To investigate the basic pathogenetic rule and mechanism of deep burn
      by constant low heat. METHODS: Animal burn model inflicted by constant low heat
      was established as follows. (1) The rats were randomly divided into groups in
      terms of temperature and duration of contact. The burn wound formation process,
      the skin tissue density and pathomorphological changes in the rats were observed
      after burn was produced on the back by contacting heat source constantly. (2) The
      subcutaneous temperature of the back was monitored at different time and
      temperatures of heat contacting by placing the thermometer under the fascia of
      the rat back. RESULTS: (1) The time of burn wound formation was shortened and the
      injury degree deepened along with the increase in the contact temperature. The
      rat skin density exhibited irregular hyperbola or triple curves. (2) The
      subcutaneous temperature exhibited a parabolic curve with fixed experimental
      conditions. CONCLUSION: (1) The sharp increase in subcutaneous temperature
      leading to degeneration and necrosis might be the primary cause of deep burn. (2)
      The regularity of the skin tissue injury was the result of multiple effects of
      heat-origin injury, increase of capillary permeability and the change in tissue
      mass.

PMID- 12515657
TI  - [The influence of lanthanum chloride on the TNFalpha expression of murine
      peritoneal macrophages stimulated by lipopolysaccharide].
AB  - OBJECTIVE: To explore the influence of lanthanum chloride on the TNFalpha
      expression of murine peritoneal macrophages stimulated by lipopolysaccharide
      (LPS). METHODS: Murine peritoneal macrophages (Mphi) were isolated, cultured and
      then stimulated by LPS. The influence of lanthanum chloride on the TNFalpha
      secretion and TNFalphamRNA expression of murine Mphi stimulated by LPS was
      determined by ELISA method and SYBR green fluorescence quantitative RT-PCR. Forty
      BALB/C mice were randomly divided into two groups and were treated by lethal dose
      of LPS and lanthanum chloride processed LPS, respectively. The mortality within 7
      days was observed. RESULTS: The TNFalpha secretion and TNFalphamRNA expression
      level of the Mphi from mice treated by lanthanum chloride processed LPS were
      obviously lower than those by LPS only (P < 0.01). The mortality of the mice
      treated by lethal dose of LPS which has been processed by lanthanum chloride was
      significantly lower than that by lethal dose of LPS only. CONCLUSION: Lanthanum
      chloride possessed the capacity of lowering down the toxicity of LPS and
      inhibiting the TNFalpha secretion and TNFalphamRNA expression in murine Mphi
      stimulated by LPS.

PMID- 12515658
TI  - [Repair of severely burned hand and wrist with abdominal thin skin flaps].
AB  - OBJECTIVE: To summarize the experience of repairing of severely burned hand and
      wrist with abdominal thin skin flaps in insertion pattern. METHODS: Twelve burn
      patients with the dorsum of the hands and wrist being severely injured were
      enrolled in this report. The donor sites of the flaps were selected on the upper
      abdomen in 4 cases and on the lower abdomen in 8 cases. The division of the flap
      pedicles was done on the 10th - 13th postoperative days. RESULTS: All the flaps
      survived except that there were two necrotic areas sized 2 cm x 2 cm and 1 cm x 1
      cm, respectively, on the distal ends of the flaps in two cases. The hand function
      and contour recovered satisfactorily after the operation. CONCLUSION: It could be
      an ideal choice for the repair of severely burned hand and wrist with abdominal
      thin skin flaps.

PMID- 12515659
TI  - [The role of LPS in the CD14 expression and the activation of Kupffer cells].
AB  - OBJECTIVE: To explore the effect of LPS on the expression of CD14 and the
      activation of Kupffer cells (KCs). METHODS: Rat KCs were isolated and cultured
      with LPS. Immunohistochemistry and RT-PCR methods were employed to determine the
      changes in the CD14 expression and the concentration of TNFalpha, IL-6 and NO in
      the supernatant of the cultured KCs with LPS. RESULTS: (1) The expression of
      CD14mRNA and the synthesis of CD14 protein in the KCs increased evidently when
      stimulated by various concentrations of LPS, and the CD14mRNA expression was
      correlated in dose-dependent manner with LPS levels. (2) The expression of
      CD14mRNA and the synthesis of CD14 protein in KCs induced by LPS (10 micro g/ml)
      increased significantly and peaked at 3 approximately 6 hours. (3) The expression
      of CD14mRNA and the synthesis of CD14 protein in freshly cultured KCs were
      obviously up-regulated by the active mediators produced by KCs after being
      stimulated by LPS. (4) The release of TNFalpha, IL-6 and NO from cultured KCs was
      evidently down-regulated by the addition of anti-CD14McAb in the presence of
      serum or by the addition of LPS in the absence of serum, but up-regulated by the
      concomitant addition of LPS and LBP. CONCLUSION: (1) The CD14mRNA expression and
      the protein synthesis in cultured KCs were closely related to LPS and the active
      mediators produced from the KCs.The increased CD14 expression was possibly caused
      by LPS, and the further increase of the expression might be closely correlated to
      the cytokines released from the KCs. (2) The KC activation by low concentration
      of LPS was CD14 dependent.

PMID- 12515660
TI  - [The manufacturing and clinical application of heterogenous acellular dermal
      matrix].
AB  - OBJECTIVE: To lower down the antigenicity of heterogenous swine acellular dermal
      tissue, and to explore the feasibility of clinical using it as a composite graft
      for human patients. METHODS: Split-thickness skin was harvested from healthy
      swines and then processed by two methods. The swine acellular dermal matrix
      (sADM) was prepared by removing cells from the skin with trypsin and Triton X
      100. Then the cross-linked sADM (sADM(1)) and non-cross-linked sADM (sADM(0))
      were embedded subcutaneously in rabbits and also transplanted onto the burn
      wounds of patients. The histological changes and also transplantation results
      were observed. RESULTS: (1) In animals with sADM(0) embedded subcutaneously, the
      grafted tissue was invaded immediately by host cells with obvious inflammatory
      reaction and tissue degradation. But there was less inflammatory reaction, and
      with no obvious skin degradation and contraction with sADM(1). (2) In ten burn
      patients with III degree burn wounds and one patient with wound in chest after
      scar removal, sADM and ultra-thin skin (UTS) composite graft were grafted on the
      wounds with autologous thin skin (ATS) and autologous razor-thin or UTS as the
      control. Nineteen pieces of composite skin of sADM with UTS were grafted on the
      wounds with survival rate of 78.9%, exhibiting no evident difference with that of
      ATS. When sADM(0) and UTS were grafed, there exhibited remarkable early
      inflammatory reaction and wound contraction with similar external appearance with
      that of UTS. Whereas when sADM(1) and UTS were grafted, there appeared less early
      inflammatory reaction and wound contraction, resulting in an even appearance and
      soft to touch similar to that with ATS. But ulceration occurred, with exposure of
      sADM(1), exposure and severe macrophage reaction to foreign body in 6 wounds of 3
      cases 12.8 +/- 6.9 weeks after sADM(1) and UTS grafting. CONCLUSION: Grafting of
      sADM as a dermal substitute of composite skin could alleviate early post-grafting
      immune reaction and improve UTS grafting results. But the delayed graft rejection
      couldn't be avoided.

PMID- 12515661
TI  - [An experimental study on the repair of full skin loss of rabbits with composite
      chitosan artificial skin].
AB  - OBJECTIVE: To investigate the practicability of repair of full skin loss of
      rabbits with composite chitosan artificial skin. METHODS: Dermal substitute was
      prepared aseptically by mixing fibroblasts with composite dermal matrix gel.
      Keratinocytes were then seeded on the substitute and submersion - cultured
      thereafter for 1 week in keratinocyte culture medium. The composite was further
      cultured for 1 approximately 2 weeks on the surface of the culture liquid to form
      artificial skin. The composite chitosan artificial skin was then grafted onto the
      full skin loss wound of rabbits. Histological changes were undertaken
      periodically by tissue sampling from the grafted wound. The systemic reaction of
      rabbits to the artificial skin was observed. RESULTS: All the grafted wounds
      healed very well without any suppuration, bleeding or infection under the grafted
      skin. No obvious immune rejection was seen. The artificial skin could cover the
      wounds for a long time with good elasticity and easy to be manipulation.
      CONCLUSION: The composite chitosan artificial skin could be an optimal biological
      dressing with good histocompatibility and easy to be manipulation.

PMID- 12515662
TI  - [An experimental study on the dermal substitute of spongy collagen membrane].
AB  - OBJECTIVE: To investigate the practicability of a spongy collagen membrane as a
      dermal substitute. METHODS: Porcine skin collagen was harvested and mixed and
      precipitated with chondroitin-6-sulfate, and then lyophilized for 48 hours to
      form sheets of highly porous membrane. The collagen membrane was embedded
      subcutaneously in SD rat's skin. The histological compatibility, the
      vascularization degree and degradation status were determined periodically by
      means of tissue sampling. RESULTS: The collagen membrane possessed some degree of
      strength and tenacity with a structure consisting of multidinous interconnecting
      pores. It was easy to manipulate. Experimental subcutaneous embedding in SD rats
      indicated that the membrane exhibited good tissue compatibility, strong tendency
      to vascularization, with no evidence of acute inflammatory reaction, and slow
      degradation rate. CONCLUSION: Spongy collagen membrane might be an optimal dermal
      substitute for wound coverage.

PMID- 12515663
TI  - [Microskin grafting by spraying in burn management].
AB  - OBJECTIVE: To explore the practicability of microskin grafting by spraying in
      burn management. METHODS: Razor thin autologous skin from pigs or burn patients
      was harvested and cut to pieces of 0.2 - 0.5 mm in size and suspended in normal
      saline. The suspension was put into a bottle with outlet and pumping device. The
      microskin suspended in the saline was sprayed to the burn wound and/or onto the
      alloskin sheets. The microskin distribution was detected by digital image
      analysis technique. In animal experiments, the burn wound development and
      pathomorphological changes after operation were observed. In burn patients who
      would receive microskin grafting, spraying method was used with the traditional
      flotation method as control. The treatment results and the operational procedures
      were compared between these two kinds of operation styles. RESULTS: The microskin
      dispersion degree with spraying was much smaller than that with flotating method.
      In animal experiment with spraying method, the wound healing time was 23.2, 24.5
      and 38.3 days in 3 groups, respectively, with the area ratio of donor to wound of
      110, 120 and 150. In clinical study, The average operating time was 133.3 min
      with spraying method and 165.6 min with flotation method respectively (P < 0.05).
      The area ratio of donor to wound was 118.8 with spraying and 17.6 with flotation
      methods, respectively (P < 0.01). The one time wound coverage rate was 92.6% with
      spraying and 79.7% with flotation methods (P < 0.01). The wound healing time was
      29.7 days with spraying and 37.3 days with flotating methods, respectively (P <
      0.05). CONCLUSION: Spraying method of microskin grafting might be a good method
      in major burn treatment. The advantages with this method included well
      distributed microskin, simpler handling, saving of donor skin, shortening of
      operating time and less time needed for the wound healing. It might be
      recommended for other wound covering materials.

PMID- 12515664
TI  - [A study of the expression of hypertrophic scar related cytoskeletal genes during
      early postburn stage].
AB  - OBJECTIVE: To screen the hypertrophic scar related cytoskeletal genes during
      early postburn stage, so as to explore their roles in postburn scar contraction.
      METHODS: cDNA microarray chips containing 4096 human cDNAs were employed to
      investigate the cytoskeletal gene expression of the scar samples from human
      postburn hypertrophic scar. Furthermore, the expression of one of the
      cytoskeletal genes in hypertrophic scar tissue was studied by in situ
      hybridization. RESULTS: Thirteen up - regulated cytoskeletal genes in 3 early
      postburn hypertrophic scar samples were identified. Moreover, the cells
      expressing human tropomyosin TM30 mRNA, one of the up - regulated cytoskeletal
      genes, were found increased in the early postburn hypertrophic scar samples.
      CONCLUSION: In this study up - regulated expression of many hypertrophic scar
      related cytoskeletal genes was found in the scar samples during early postburn
      stage, and they might be important factors leading to postburn hypertrophic scar
      formation and contraction.

PMID- 12515665
TI  - [An experimental study of the inhibitory effects of Tripterygium extract (LLZ) on
      hypertrophic scar - derived fibroblasts].
AB  - OBJECTIVE: To explore the effects of Tripterygium extract (LLZ) on postburn
      hypertrophic scar - derived fibroblasts, so as to provide us an experimental
      support for the treatment of postburn hypertrophic scar. METHODS: Hypertrophic
      scar - derived fibroblasts were harvested and cultured in vitro. A serial
      concentrations of LLZ (5 x 10(-3), 5 x 10(-4), 5 x 10(-5), 5 x 10(-6) g/L) were
      added to the culture media. The cellular morphology, proliferating activity and
      the cytotoxicity of the drug were observed after 24 hours of culture. RESULTS:
      The fibroblast morphology could be altered by any concentration of LLZ solution.
      Furthermore, the cell count and the cellular proliferating activity were all
      decreased obviously by the treatment of LLZ. CONCLUSION: The cell morphology and
      proliferation activity of postburn scar-derived fibroblasts could all be
      inhibited by LLZ, and it was the result of its toxic effects.

PMID- 12515666
TI  - [The effects of postburn fluid resuscitation on the pathohistological and
      ultrastructural changes of multiple organs with dysfunction in severely burned
      dogs].
AB  - OBJECTIVE: To investigate the effects of postburn fluid resuscitation on the
      pathohistological and ultrastructural changes of multiple organs with dysfunction
      in severely burned dogs. METHODS: Forty - four mongrel dogs were randomly divided
      into four groups: (1) immediate infusion (II, n = 8), (2) delayed infusion (DI, n
      = 15), (3) no infusion (NI, n = 14), (4) normal control (NC, n = 7). The dogs
      were inflicted with 50% TBSA III degree flame burn produced by napalm in
      concentration of 30g/L burning for 30 seconds on the back. Small pieces of tissue
      samples of heart, lungs, liver, kidneys and gastrointestinal tract were taken
      from injured dogs at 72 postburn hours (PBHs) or moribund stage for the
      examination with light microscope (LM) and transmission electron microscope
      (TEM). RESULTS: Different degrees of blood circulation disturbance and
      degenerative changes were found in all above internal organs. These changes were
      more evident in DI than in II and NI groups. CONCLUSION: Delayed postburn fluid
      resuscitation could induce multiple organ dysfunction in early postburn stage.

PMID- 12515667
TI  - [The relationship between use of the antibiotics in a burn unit and the change of
      the drug-resistance of Staphylococcus aureus].
AB  - OBJECTIVE: To investigate the relationship between the use of antibiotics in a
      burn unit and the change in the drug - resistance of Staphylococcus aureus (S.
      aureus). METHODS: By calculating the defined daily doses (DDD) of accumulated
      consumption of antibiotics per unit time and expense consumption, the use of
      different kinds of antibiotics in a burn unit in recent five years was analyzed,
      and correlation analysis between the change of antibiotics consumption amount and
      the change in drug - resistance level of S. aureus were carried out. RESULTS:
      Amikacin, gentamycin and cephazolin were the commonest antibiotics used in our
      burn unit. They were relatively cheaper than some other antibiotics. The
      consumption amount of compound antibiotics application was negatively correlated
      with the penicillin resistance level of S. aureus. Seven correlation coefficients
      between the consumption of first generation cephalosporins and seven
      coefficiences of resistance rate of S. aureus were negative. The consumption
      amount of the 3rd generation of cephalosporin application was positively related
      to the resistance of S. aureus to erythromycin and oxacillin. CONCLUSION:
      Accumulated DDD might be one of the ideal indices of reflecting antibiotic use.
      The changes in the consumption amount of the 1st and 3rd generation of
      cephalosporins containing beta-lactamase-inhibitor might affect the drug
      resistance levels of S. aureus to some degree.

PMID- 12515668
TI  - [The modulating effects of transfected IkappaBalpha gene on the NF-kappaB
      activity of hepatic tissue in scalded rats].
AB  - OBJECTIVE: To explore the modulating effects mediated by recombinant IkappaBalpha
      gene by adenovirus vector transfection on the NF-kappaB activity of hepatic
      tissue in scalded rats. METHODS: After being primed by recombinant defect
      adenovirus (AdIkappaBalpha) vector, the rats were scalded. The hepatic tissue was
      harvested at different time points and the nuclear protein was extracted and
      reacted with [r(-23) P] ATP labelled NF-kB specific probe. NF-Kb/DNA combining
      activity was determined with electrophoretic mobility shifty assay (EMSA). The
      total RNA in hepatic tissue was extracted and the expressions of IL-1beta and
      TNFalpha mRNA were determined with RT-PCR. RESULTS: When compared to those in
      normal control, the NF-kappaB/DNA combining activity increased significantly in
      scalded rats at half an hour after scalding, and it lasted for 24 PBDs with
      rather strong activity. But in AdIkappaBalpha priming group, the rat NF
      kappaB/DNA binding activity was slightly higher than that of normal control
      group, but was obviously lower than that of scalding group. CONCLUSION: The
      intracellular NF-kappaB in hepatic tissue was activated rapidly after that the
      rats were severely scalded, and the expression of IL-1beta and TNFalpha was
      enhanced significantly simultaneously. Priming of AdIkappaBalpha could evidently
      inhibit the activation of hepatic tissue NF-kB in rats injured by severe
      scalding, and down-regulated the expressions of IL-1beta and TNFalpha.

PMID- 12515669
TI  - [The postburn change in hypothalamic paraventricular beta-endorphin and the roles
      of delta-receptor in scalded rats].
AB  - OBJECTIVE: To investigate the postburn change in hypothalamic paraventricular
      beta-endorphin and the roles of delta-receptor in scalded rats. METHODS: Male
      Sprague-Dawley (SD) rats were randomly divided into 3 groups, i.e. ICI174864,
      DPDPE and control groups. The rats were inflicted with 20% TBSA of III degree
      scalding on the back by boiling (100 degrees ) water. The postburn change in the
      tissue content of the hypothalamic paraventricular beta-endorphin was determined
      by radioimmuno assay (RIA). The effects of delta-receptor in scalded shock rats
      were investigated by observing the change of the rats'survival time and cardiac
      indices after the micro-injection of delta-receptor agonist DPDPE or antagonist
      ICI174864 into the hypothalamic paraventricle. RESULTS: (1) The tissue content of
      the hypothalamic paraventricular beta-endorphin increased significantly (P <
      0.01) at 1, 2 and 4 postburn hours (PBHs) in the scalded rats. (2) When compared
      with that of control group, the ratio of the cardiovascular parameters [mean
      arterial pressure (MAP), dp/dt(max) and HR] were obviously increased at different
      time points in rats with pre-injection of ICI174864 whereas the ratio was
      decreased when DPDPE was used. Nevertheless, the change in the heart rate ratio
      was not obvious whether ICI174864 or DPDPE was used. (3) The average animal
      survival time in ICI174864 group was much longer than that in DPDPE group.
      CONCLUSION: An excessive increase in hypothalamic paraventricular beta-endorphin
      was one of the factors leading to the aggravation of burn shock and earlier
      death. delta-receptor located in the tissue might have played important roles in
      the mediation of the action of hypothalamic paraventricular beta-endorphin. It is
      beneficial to antagonize the action of delta-receptor for the correction of burn
      shock and for the prolongation of the of life of animals.

PMID- 12515670
TI  - [The effects of recombinant human growth hormone (rhGH) on the serum levels of
      cytokines in severely burned patients].
AB  - OBJECTIVE: To explore the effects of recombinant human growth hormone (rhGH) on
      the serum levels of cytokines in severely burned patients. METHODS: Thirty-six
      burn patients were enrolled in the study and were randomly divided into 3 groups
      according to the rhGH dosage used, i.e. small (0.3 IU.kg(-1).d(-1), A), large
      (0.6 IU.kg(-1).d(-1), B) dose groups and control group (C, with normal saline).
      The rhGH was administered beginning from 3 postburn days (PBDs) and lasted for 20
      days. The dynamic changes in the serum levels of TNFalpha, IL-6, IL-8 and LPS at
      different time points were observed. RESULTS: When compared with those in C
      group, the serum levels of TNFalpha, IL-6 in A, B groups were decreased,
      especially in B group with earlier decrease and bigger range (P < 0.01).
      Simultaneously, the serum LPS level was decreased accordingly with evident
      positive correlation with the change in those cytokines (r = 0.9723, P < 0.01).
      But there was no obvious difference in serum IL-8 level among A, B and C groups
      (P > 0.05). CONCLUSION: rhGH might decrease the production of postburn
      inflammatory mediators, especially in higher dose in dose-dependent manner for
      some degree. The clinical application of rhGH might be a supplementary measure in
      preventing and ameliorating postburn SIRS and MODS in severely burned patients.

PMID- 12515671
TI  - Molecular techniques for studying gene expression in carcinogenesis.
AB  - Many genes and signaling pathways controlling cell proliferation, death,
      differentiation, and genomic integrity are involved in cancer development.
      Various methods are available for detection and quantification of messenger RNA.
      Older methods such as Northern blots, nuclease protection, plaque hybridization,
      and slot blots suffer from being inherently serial, measure a single mRNA at a
      time, or being difficult to automate. New techniques for analysis of gene
      expression include: (a) comprehensive open systems such as serial analysis of
      gene expression (SAGE), differential display (DD) analysis, RNA arbitrarily
      primer (RAP)-PCR, restriction endonucleolytic analysis of differentially
      expressed sequences (READS), amplified restriction fragment-length polymorphism
      (AFLP), total gene expression analysis (TOGA), and use of internal standard
      competitive template primers (CTs) in a quantitative multiplex RT-PCR method
      [StaRT-(PCR)], and (b) focused closed systems such as: high density cDNA filter
      hybridization (HDFCA) analysis, suppression subtractive hybridization (SSH),
      differential screening (DS), several forms of high-density cDNA arrays, or
      oligonucleotide chips, and tissue microarrays. Sometimes, a combination of these
      systems is used to enhance the sensitivity and specificity of the assays. While
      closed systems are excellent for the initial screening of large number of
      sequences, the value of the information generated is generally limited to an
      often arbitrarily chosen known sequence. On the other hand, only the open system
      platform has the potential to evaluate the expression patterns of tens of
      thousands of genes that have not yet been cloned or partially sequenced in a
      quantitative manner. A cost analysis of the most commonly used expression
      technologies is provided. A method for purifying tumors from surrounding stroma
      and normal tissue employing laser microdissection, and subsequent RNA
      isolation/amplification from few cells employing sensitive kits are also
      discussed.

PMID- 12515672
TI  - The dual effect of the particulate and organic components of diesel exhaust
      particles on the alteration of pulmonary immune/inflammatory responses and
      metabolic enzymes.
AB  - Exposure to diesel exhaust particles (DEP) is an environmental and occupational
      health concern. This review examines the cellular actions of the organic and the
      particulate components of DEP in the development of various lung diseases. Both
      the organic and the particulate components cause oxidant lung injury. The
      particulate component is known to induce alveolar epithelial damage, alter thiol
      levels in alveolar macrophages (AM) and lymphocytes, and activate AM in the
      production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The
      organic component, on the other hand, is shown to generate intracellular ROS,
      leading to a variety of cellular responses including apoptosis. There are a
      number of differences between the biological actions exerted by these two
      components. The organic component is responsible for DEP induction of cytochrome
      P450 family 1 enzymes that are critical to the polycyclic aromatic hydrocarbons
      (PAH) and nitro-PAH metabolism in the lung as well as in the liver. The
      particulate component, on the other hand, causes a sustained down-regulation of
      CYP2B1 in the rat lung. The significance of this effect on pulmonary metabolism
      of xenobiotics and endobiotics remains to be seen, but may prove to be an
      important factor governing the interplay of the pulmonary metabolic and
      inflammatory systems. Long-term exposures to various particles including DEP,
      carbon black (CB), TiO2, and washed DEP devoid of the organic content, have been
      shown to produce similar tumorigenic responses in rodents. There is a lack of
      correlation between tumor development and DEP chemical-derived DNA adduct
      formation. But the organic component has been shown to generate ROS that produce
      8-hydroxydeoxyguanosine (8-OHdG) in cell culture. The organic, but not the
      particulate, component of DEP suppresses the production of pro-inflammatory
      cytokines by AM and the development of Th1 cell-mediated immunity. The mechanism
      for this effect is not yet clear, but may involve the induction of heme oxygenase
      1 (HO-1), a cellular genetic response to oxidative stress. Both the organic and
      the particulate components of DEP enhance respiratory allergic sensitization.
      Part of the DEP effects may be due to a depletion of glutathione in lymphocytes.
      The organic component, which is shown to induce IL-4 and IL-10 productions, may
      skew the immunity toward Th2 response, whereas the particulate component may
      stimulate both the Th1 and Th2 responses. In conclusion, the literature shows
      that the particulate and organic components of DEP exhibit different biological
      actions but both involve the induction of cellular oxidative stress. Together,
      these effects inhibit cell-mediated immunity toward infectious agents, exacerbate
      respiratory allergy, cause DNA damage, and under long-term exposure, induce the
      development of lung tumors.

PMID- 12515673
TI  - Environmental carcinogenic polycyclic aromatic hydrocarbons: photochemistry and
      phototoxicity.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a class of environmental contaminants
      that has long been of interest in the fields of organic chemistry, theoretical
      chemistry, physical chemistry, environmental science, toxicology, cancer
      research, and energy sciences. Concerning environmental science and cancer
      research, majority of the research has focused on the occurrence, environmental
      fate, degradation/remediation, chemical transformation, genotoxicity, metabolism
      and metabolic activation, DNA adduct formation, mutagenesis, and carcinogenesis.
      Although many books and reviews on these subjects have been published, PAH
      photochemistry and phototoxicity have received much less attention. Therefore, it
      is intended for this article to provide an up-to-date source of photochemical
      reaction, photo-transformation, and phototoxicity of PAHs and their oxygenated,
      nitrated, halogenated, and amino substituted derivatives on a molecular basis. A
      perspective for future work is also discussed.

PMID- 12515674
TI  - Pathogen survival trajectories: an eco-environmental approach to the modeling of
      human campylobacteriosis ecology.
AB  - Campylobacteriosis, like many human diseases, has its own ecology in which the
      propagation of human infection and disease depends on pathogen survival and
      finding new hosts in order to replicate and sustain the pathogen population. The
      complexity of this process, a process common to other enteric pathogens, has
      hampered control efforts. Many unknowns remain, resulting in a poorly understood
      disease ecology. To provide structure to these unknowns and help direct further
      research and intervention, we propose an eco-environmental modeling approach for
      campylobacteriosis. This modeling approach follows the pathogen population as it
      moves through the environments that define the physical structure of its ecology.
      In this paper, we term the ecologic processes and environments through which
      these populations move "pathogen survival trajectories." Although such a modeling
      approach could have veterinary applications, our emphasis is on human
      campylobacteriosis and focuses on human exposures to Campylobacter through feces,
      food, and aquatic environments. The pathogen survival trajectories that lead to
      human exposure include ecologic filters that limit population size, e.g., cooking
      food to kill Campylobacter. Environmental factors that influence the size of the
      pathogen reservoirs include temperature, nutrient availability, and moisture
      availability during the period of time the pathogen population is moving through
      the environment between infected and susceptible hosts. We anticipate that the
      modeling approach proposed here will work symbiotically with traditional
      epidemiologic and microbiologic research to help guide and evaluate the
      acquisition of new knowledge about the ecology, eventual intervention, and
      control of campylobacteriosis.

PMID- 12515675
TI  - In ovo exposure to o,p -DDE affects sexual development but not sexual
      differentiation in Japanese medaka (Oryzias latipes).
AB  - Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and
      its metabolites dichlorodiphenyldichloroethylene (DDE) and
      dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at
      concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed
      to exert its effects through binding to the estrogen receptor. The limited
      toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility
      of fishes. We conducted an egg injection study using the d-rR strain of medaka
      and environmentally relevant concentrations of o,p -DDE to examine its effects on
      sexual differentiation and development. The gonads of exposed fish showed no
      evidence of sex reversal or intersex. However, other gonad abnormalities occurred
      in exposed individuals. Females exhibited few vitellogenic oocytes and increased
      atresia. Male testes appeared morphologically normal but were very small.
      Gonadosomatic index values for both sexes were lower for exposed fish. Our
      observations of abnormal female and very small male gonads after in ovo o,p -DDE
      exposure may be indicative of effects on early endocrine processes important for
      normal ovarian and testicular development.

PMID- 12515676
TI  - Polycyclic aromatic hydrocarbon-induced cytotoxicity in cultured rat Sertoli
      cells involves differential apoptotic response.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent
      environmental contaminants. Some PAHs are carcinogens and may affect the male
      reproductive system. Therefore, we exposed cultured rat Sertoli cells to a
      variety of PAHs to determine possible direct toxic effects on the cells of the
      seminiferous epithelium. Sertoli cells were chosen because they support germ cell
      development and maintain spermatogenesis. Sertoli cells were isolated from 19-21
      day-old male rats and cultured in medium containing 0.08% dimethylsulfoxide as
      vehicle or in the presence of a variety of PAHs. In the first set of experiments,
      cultured Sertoli cells were incubated in the presence of 10(-4) M, 10(-6 )M, 10(
      8) M, 10(-12) M, and 10(-16) M fluoranthene (FL) for 24 hr. After 24 hr, FL at
      10(4), 10(-6), and 10(-8) M killed significant numbers of Sertoli cells as
      revealed by cell viability determinations. Sertoli cells cultured in the presence
      of 10(-6) M and 10(-8) M FL showed morphologic changes. Cell protein levels were
      decreased and lactate production in the medium increased in a concentration
      dependent manner. In addition, Sertoli cells exposed to 10(6) M and 10(-8) M FL
      exhibited altered F-actin and alpha-tubulin distributions compared with untreated
      controls. Because FL killed about 62% of cells at 10(-4) M (100 micro g/mL) and
      48% of cells at 10(-6) M (1 micro g/mL), increased lactate production about 3
      fold at both concentrations, and decreased cell protein by half at 10(-4) M (100
      micro g/mL), we decided to use a range of concentrations between 10 and 100 micro
      g/mL for the second set of experiments using benz[a]anthracene (BaA),
      benzo[a]pyrene (BaP), or benzo[b]fluoranthene (BbF). After 24 hr, BaA (100 micro
      g/mL), BaP (50 and 100 micro g/mL), and BbF (100 micro g/mL) significantly
      increased lactate level in the medium in a concentration-dependent manner. In a
      third set of experiments, cells were treated in culture uniformly with only 10
      micro g/mL FL, BaA, BaP, or BbF for 24 hr. The cytotoxic effects exerted by these
      PAHs tested resulted in different apoptotic responses as characterized by in situ
      fluorescence staining. Microscopic analysis of apoptotic cells demonstrated
      nuclei of reduced size and labeled 3 -OH DNA ends when Sertoli cells had been
      incubated for 24 hr with 10 micro g BaP or BbF, but not with vehicle, media, FL,
      or BaA. Thus, our results demonstrate that the toxic effects of BaA and BbF on
      Sertoli cells are exerted through apoptosis, whereas FL and BaA do not elicit the
      apoptotic response.

PMID- 12515677
TI  - National maps of the effects of particulate matter on mortality: exploring
      geographical variation.
AB  - In this paper, we present national maps of relative rates of mortality associated
      with short-term exposure to particulate matter < 10 micro m in aerodynamic
      diameter (PM(10)). We report results for 88 of the largest metropolitan areas in
      the United States from 1987 to 1994 for all-cause mortality, combined
      cardiovascular and respiratory deaths, and other causes of mortality. Maximum
      likelihood estimates of the relative rate of mortality associated with PM(10)and
      the degree of statistical uncertainty were obtained for each of the 88 cities by
      fitting a separate log-linear regression of the daily mortality rate on air
      pollution level and potential confounders. We obtained Bayesian estimates of the
      relative rates by fitting a hierarchical model that takes into account spatial
      correlation among the true city-specific relative rates. We found that daily
      variations of PM(10) are positively associated with daily variations of
      mortality. In particular, the relative rate estimates of cardiovascular and
      respiratory mortality associated with PM(10) are larger on average than the
      relative rate estimates of all-cause and other-cause mortality. The estimated
      increase in the relative rate of death from cardiovascular and respiratory
      mortality, all-cause mortality, and other-cause mortality were 0.31% (95%
      posterior interval, 0.15-0.5), 0.22% (95% posterior interval, 0.1-0.38), and
      0.13% (95% posterior interval, -0.05 to 0.29), respectively. Bayesian estimates
      of the city-specific relative rates ranged from 0.23% to 0.35% for cardiovascular
      and respiratory mortality, from 0.18% to 0.27% for all causes, and from 0.10% to
      0.20% for other causes of mortality. The spatial characterization of effects
      across cities offers the potential to identify factors that could influence the
      effect of PM(10) on health, including particle characteristics, offering insights
      into mechanisms by which PM(10) causes adverse health effects.

PMID- 12515678
TI  - Air pollution and daily mortality in a city with low levels of pollution.
AB  - The concentration-response relationship between daily ambient inhalable particle
      (particulate matter less than or equal to 10 micro m; PM(10)) concentrations and
      daily mortality typically shows no evidence of a threshold concentration below
      which no relationship is observed. However, the power to assess a relationship at
      very low concentrations of PM(10) has been limited in studies to date. The
      concentrations of PM(10) and other air pollutants in Vancouver, British Columbia,
      Canada, from January 1994 through December 1996 were very low: the 50th and 90th
      percentiles of daily average PM(10) concentrations were 13 and 23 micro g/m(3),
      respectively, and 27 and 39 ppb, respectively, for 1-hr maximum ozone. Analyses
      of 3 years of daily pollution (PM(10), ozone, sulfur dioxide, nitrogen dioxide,
      and carbon monoxide) concentrations and mortality counts showed that the dominant
      associations were between ozone and total mortality and respiratory and
      cardiovascular mortality in the summer, and between nitrogen dioxide and total
      mortality in the winter, although some association with PM(10) may also have been
      present. We conclude that increases in low concentrations of air pollution are
      associated with increased daily mortality. These findings may support the notion
      that no threshold pollutant concentrations are present, but they also raise
      concern that these effects may not be effects of the measured pollutants
      themselves, but rather of some other factor(s) present in the air pollution
      meteorology mix.

PMID- 12515679
TI  - A 2-year dose-response study of lesion sequences during hepatocellular
      carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical
      dichloroacetic acid.
AB  - Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat.
      Given the carcinogenic potential of DCA in rodent liver and the known
      concentrations of this compound in drinking water, reliable biologically based
      models to reduce the uncertainty of risk assessment for human exposure to DCA are
      needed. Development of such models requires identification and quantification of
      premalignant hepatic lesions, identification of the doses at which these lesions
      occur, and determination of the likelihood that these lesions will progress to
      cancer. In this study we determined the dose response of histopathologic changes
      occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks.
      Lesions were classified as foci of cellular alteration smaller than one liver
      lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one
      liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or
      carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed
      that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD
      demonstrated neoplastic progression with time; and (c)) independent of DCA dose
      and length of exposure effects, some toxic/adaptive changes in non-involved liver
      were related to this neoplastic progression. A lesion sequence for carcinogenesis
      in male B6C3F(1) mouse liver has been proposed that will enable development of a
      biologically based mathematical model for DCA. Because all classes of
      premalignant lesions and CAs were found at both lower and higher doses, these
      data are consistent with the conclusion that nongenotoxic mechanisms, such as
      negative selection, are relevant to DCA carcinogenesis at lower doses where DCA
      genotoxicity has not been observed.

PMID- 12515680
TI  - Comparison of polychlorinated biphenyl levels across studies of human
      neurodevelopment.
AB  - Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in
      the food chain, and detectable amounts are in the blood of almost every person in
      most populations that have been examined. Extensive evidence from animal studies
      shows that PCBs are neurotoxins, even at low doses. Interpretation of human data
      regarding low-level, early-life PCB exposure and subsequent neurodevelopment is
      problematic because levels of exposure were not similarly quantified across
      studies. We expressed the exposure levels from 10 studies of PCB and
      neurodevelopment in a uniform manner using a combination of data from original
      investigators, laboratory reanalyses, calculations based on published data, and
      expert opinion. The mainstay of our comparison was the median level of PCB 153 in
      maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies
      ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110
      ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies
      overlapped substantially, (b)) exposure levels in the Faroe Islands study were
      about 3-4-fold higher than in most other studies, and (c)) the exposure levels in
      the two recent U.S. studies were about one-third of those in the four earlier
      U.S. studies or recent Dutch, German, and northern Quebec studies. Our results
      will facilitate a direct comparison of the findings on PCBs and neurodevelopment
      when they are published for all 10 studies.

PMID- 12515681
TI  - Effect of indoor air pollution from biomass combustion on prevalence of asthma in
      the elderly.
AB  - In this study I examined the effect of cooking smoke on the reported prevalence
      of asthma among elderly men and women greater than or equal to 60 years old). The
      analysis is based on 38,595 elderly persons included in India's second National
      Family Health Survey conducted in 1998-1999. Effects of exposure to cooking
      smoke, ascertained by type of fuel used for cooking (biomass fuels, cleaner
      fuels, or a mix of biomass and cleaner fuels), on the reported prevalence of
      asthma were estimated using logistic regression. Because the effects of cooking
      smoke are likely to be confounded with effects of age, tobacco smoking,
      education, living standard, and other such factors, the analysis was carried out
      after statistically controlling for such factors. Results indicate that elderly
      men and women living in households using biomass fuels have a significantly
      higher prevalence of asthma than do those living in households using cleaner
      fuels [odds ratio (OR) = 1.59; 95% confidence interval (95% CI), 1.30-1.94], even
      after controlling for the effects of a number of potentially confounding factors.
      Active tobacco smoking was also associated with higher asthma prevalence in the
      elderly, but not environmental tobacco smoke. Availability of a separate kitchen
      in the house and a higher living standard of the household were associated with
      lower asthma prevalence. The adjusted effect of cooking smoke on asthma was
      greater among women (OR = 1.83; 95% CI, 1.32-2.53) than among men (OR = 1.46; 95%
      CI, 1.14-1.88). The findings have important program and policy implications for
      countries such as India, where large proportions of the population rely on
      polluting biomass fuels for cooking and space heating. More epidemiologic
      research with better measures of smoke exposure and clinical measures of asthma
      is needed to validate the findings.

PMID- 12515682
TI  - Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort.
AB  - Evidence is growing that indoor pesticide exposure is of considerable magnitude
      in the United States and that pesticide concentrations may be especially high in
      urban areas. Of particular concern is exposure of pregnant women because animal
      data suggest that exposure to pesticides during pregnancy and early life may
      impair neurodevelopment in the offspring. To investigate the relationship between
      prenatal exposure to indoor pesticides and infant growth and development, we are
      conducting a prospective, multiethnic cohort study of mothers and infants
      delivered at Mount Sinai Hospital in New York City. This article provides data on
      pesticide exposure based on questionnaire items and analysis of maternal urinary
      metabolite levels among 386 women. Both the questionnaire and laboratory data
      revealed that exposure to indoor pesticides was considerable. The proportion of
      women estimated from questionnaire data as having been exposed during pregnancy
      to indoor pesticides (approximately 70%) was somewhat lower than the 80-90% of
      American households who reportedly used pesticides in previous surveys, but some
      of the latter surveys included both indoor and outdoor pesticide use. Urinary
      metabolite levels of 3,5,6-trichloro-2-pyridinol (TCPy; median = 11.3 micro g/g
      creatinine), phenoxybenzoic acid (PBA; median =19.3 micro g/g creatinine), and
      pentachlorophenol (PCP; median =7.3 micro g/g creatinine) were higher than those
      reported in other studies of adults in the United States. Furthermore, no
      associations were evident between the pesticide questionnaire data and the
      urinary metabolites. Assessments of sociodemographic and building characteristics
      with questionnaire data and the metabolite levels revealed no consistent trends.
      Significant temporal variations were observed for urinary PBA but not TCPy or
      PCP. The temporal variations for PBA were consistent with seasonal spraying of
      pyrethroid pesticides. These data underscore the need to assess the potentially
      adverse effects of pesticide exposure on fetuses and infants and the importance
      of finding alternative methods for pest management to reduce pesticide exposures.

PMID- 12515683
TI  - Restructuring nuclear regulations.
AB  - Nuclear regulations are a subset of social regulations (laws to control
      activities that may negatively impact the environment, health, and safety) that
      concern control of ionizing radiation from radiation-producing equipment and from
      radioactive materials. The impressive safety record among nuclear technologies is
      due, in no small part, to the work of radiation safety professionals and to a
      protection system that has kept pace with the rapid technologic advancements in
      electric power generation, engineering, and medicine. The price of success,
      however, has led to a regulatory organization and philosophy characterized by
      complexity, confusion, public fear, and increasing economic costs. Over the past
      20 years, regulatory costs in the nuclear sector have increased more than 250% in
      constant 1995 U.S. dollars. Costs of regulatory compliance can be reduced
      sharply, particularly when health and environmental benefits of risk reduction
      are questionable. Three key regulatory areas should be closely examined and
      modified to improve regulatory effectiveness and efficiency: a) radiation
      protection should be changed from a risk-based to dose-based system; b) the U.S.
      government should adopt the modern metric system (International System of Units),
      and radiation quantities and units should be simplified to facilitate
      international communication and public understanding; and c) a single,
      independent office is needed to coordinate nuclear regulations established by
      U.S. federal agencies and departments.

PMID- 12515684
TI  - Production of proinflammatory mediators by indoor air bacteria and fungal spores
      in mouse and human cell lines.
AB  - We compared the inflammatory and cytotoxic responses caused by household mold and
      bacteria in human and mouse cell lines. We studied the fungi Aspergillus
      versicolor, Penicillium spinulosum, and Stachybotrys chartarum and the bacteria
      Bacillus cereus, Pseudomonas fluorescens, and Streptomyces californicus for their
      cytotoxicity and ability to stimulate the production of inflammatory mediators in
      mouse RAW264.7 and human 28SC macrophage cell lines and in the human A549 lung
      epithelial cell line in 24-hr exposure to 10(5), 10(6), and 10(7) microbes/mL. We
      studied time dependency by terminating the exposure to 10(6) microbes/mL after 3,
      6, 12, 24, and 48 hr. We analyzed production of the cytokines tumor necrosis
      factor-alpha and interleukins 6 and 1ss (TNF-alpha, IL-6, IL-1ss, respectively)
      and measured nitric oxide production using the Griess method, expression of
      inducible NO-synthase with Western Blot analysis, and cytotoxicity with the MTT
      test. All bacteria strongly induced the production of TNF-alpha, IL-6 and, to a
      lesser extent, the formation of IL-1ss in mouse macrophages. Only the spores of
      Str. californicus induced the production of NO and IL-6 in both human and mouse
      cells. In contrast, exposure to fungal strains did not markedly increase the
      production of NO or any cytokine in the studied cell lines except for Sta.
      chartarum, which increased IL-6 production somewhat in human lung epithelial
      cells. These microbes were less cytotoxic to human cells than to mouse cells. On
      the basis of equivalent numbers of bacteria and spores of fungi added to cell
      cultures, the overall potency to stimulate the production of proinflammatory
      mediators decreased in the order Ps. fluorescens > Str. californicus > B. cereus
      > Sta. chartarum > A. versicolor > P. spinulosum. These data suggest that
      bacteria in water-damaged buildings should also be considered as causative agents
      of adverse inflammatory effects.

PMID- 12515685
TI  - Relationship between reproductive success and male plasma vitellogenin
      concentrations in cunner, Tautogolabrus adspersus.
AB  - The gene for vitellogenin, an egg yolk protein precursor, is usually silent in
      male fish but can be induced by estrogen exposure. For this reason, vitellogenin
      production in male fish has become a widely used indicator of exposure to
      exogenous estrogens or estrogen mimics in the aquatic environment. The utility of
      this indicator to predict impacts on fish reproductive success is unclear because
      information on the relationship between male plasma vitellogenin and reproductive
      end points in male and female fish is limited. In the research reported in this
      article, we investigated whether the presence of male plasma vitellogenin is a
      reliable indicator of decreased reproductive success in mature fish. Adult and
      sexually mature male and female cunner (Tautogolabrus adspersus) were exposed to
      17ss-estradiol, ethynylestradiol, or estrone, three steroidal estrogens that
      elicit the vitellogenic response. Data were gathered and pooled on egg
      production, egg viability, egg fertility, sperm motility, and male plasma
      vitellogenin concentrations. All males, including two with plasma vitellogenin
      levels exceeding 300 mg/mL, produced motile sperm. Neither percent fertile eggs
      nor percent viable eggs produced by reproductively active fish demonstrated a
      significant correlation with male plasma vitellogenin concentrations. Male
      gonadosomatic index and average daily egg production by females showed
      significant, but weak, negative correlation with male plasma vitellogenin
      concentrations. Results suggest that male plasma vitellogenin expression is not a
      reliable indicator of male reproductive dysfunction in adult cunner exposed to
      estrogens for 2-8 weeks during their reproductive season, at least in relation to
      capacity to produce motile sperm or fertilize eggs. Male plasma vitellogenin
      expression may serve as an indicator of reduced female reproductive function
      caused by estrogen exposure.

PMID- 12515686
TI  - Bisphenol A levels in human urine.
AB  - The estrogenic effects of bisphenol A (BPA) have been reported in human cells (E
      screen assays) and in (italic)in vivo(/italic) studies of rodents, although the
      latter reports remain controversial, as do the exposure levels and adverse health
      effects of BPA in humans. In this study we report on an analytical high
      performance liquid chromatography/fluorescence method for BPA and its conjugate
      in human urine and on the application of this method in two student cohorts.
      Urine, along with information on smoking, alcohol intake, and coffee/tea
      consumption, was collected in two different years from two different groups of
      university students, 50 in 1992 and 56 in 1999. Overall, the urinary BPA levels
      in the students in 1992 were significantly higher than were those in 1999. The
      BPA levels were also positively correlated with coffee and tea consumption in the
      1992 cohort but not in the 1999 cohort. We speculate that recent changes made in
      Japan regarding the interior coating of cans used to package these beverages may
      partly explain these findings.

PMID- 12515687
TI  - Workshop report: environmental exposures and cancer prevention.
AB  - The Workshop on Environmental Exposures and Cancer was held by Cancer Care
      Ontario (CCO) 25-26 April 2001. An expert panel convened to achieve consensus on
      a list of important environmental exposures, priority environmental exposures in
      Ontario, and recommendations for CCO in the areas of surveillance, research, and
      prevention activities to address these environmental exposures. Panel members
      developed a working definition of environmental exposure and criteria to
      prioritize the identified exposures. The process followed in the workshop
      provided CCO with important direction for its surveillance, research, and
      prevention activities to address environmental exposures and cancer. It is hoped
      that the environmental exposures and the opportunities identified through this
      workshop process will guide policy makers, program personnel, and researchers
      interested in and struggling with the challenges associated with surveillance,
      research, and prevention of environmental exposures.

PMID- 12515688
TI  - Lessons from the polybrominated diphenyl ethers (PBDEs): precautionary principle,
      primary prevention, and the value of community-based body-burden monitoring using
      breast milk.
AB  - Levels of chemicals in humans (body burdens) are useful indicators of
      environmental quality and of community health. Chemical body burdens are easily
      monitored using breast milk samples collected from first-time mothers
      (primiparae) with infants 2-8 weeks of age. Currently, there is no body-burden
      monitoring program using breast milk in the United States, although ad hoc
      systems operate successfully in several European countries. In this article we
      describe the value of such monitoring and important considerations of how it
      might be accomplished, drawing from our experiences with pilot monitoring
      projects. Breast milk has several advantages as a sampling matrix: It is simple
      and noninvasive, with samples collected by the mother. It monitors body burdens
      in reproductive-age women and it estimates in utero and nursing-infant exposures,
      all important to community health. Time-trend data from breast milk monitoring
      serve as a warning system that identifies chemicals whose body burdens and human
      exposures are increasing. Time trends also serve as a report card on how well
      past regulatory actions have reduced environmental chemical exposures. Body
      burden monitoring using breast milk should include educational programs that
      encourage breast-feeding. Finally, and most important, clean breast milk matters
      to people and leads to primary prevention--the limiting of chemical exposures. We
      illustrate these advantages with polybrominated diphenyl ethers (PBDEs), a
      formerly obscure group of brominated flame retardants that rose to prominence and
      were regulated in Sweden when residue levels were found to be rapidly increasing
      in breast milk. A community-based body-burden monitoring program using breast
      milk could be set up in the United States in collaboration with the Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC). WIC has a
      large number of lactating first-time mothers: It has 6,000 clinics nationwide and
      serves almost half (47%) the infants born in the United States. Educational
      programs (e.g., those run by WIC) are needed that encourage breast-feeding,
      especially in lower-income communities where breast-feeding rates are low and
      where breast-feeding may help protect the infant from the effects of
      environmental chemical exposures. Education is also needed about reducing
      chemical body burdens. A body-burden monitoring program would provide valuable
      data on time trends, background levels, and community hot spots in need of
      mitigation and follow-up health studies; develop analytic methods for new
      chemicals of concern; and archive breast milk samples for future analyses of
      other agents.

PMID- 12515689
TI  - Time-location analysis for exposure assessment studies of children using a novel
      global positioning system instrument.
AB  - Global positioning system (GPS) technology is used widely for business and
      leisure activities and offers promise for human time-location studies to evaluate
      potential exposure to environmental contaminants. In this article we describe the
      development of a novel GPS instrument suitable for tracking the movements of
      young children. Eleven children in the Seattle area (2-8 years old) wore custom
      designed data-logging GPS units integrated into clothing. Location data were
      transferred into geographic information systems software for map overlay,
      visualization, and tabular analysis. Data were grouped into five location
      categories (in vehicle, inside house, inside school, inside business, and
      outside) to determine time spent and percentage reception in each location.
      Additional experiments focused on spatial resolution, reception efficiency in
      typical environments, and sources of signal interference. Significant signal
      interference occurred only inside concrete/steel-frame buildings and inside a
      power substation. The GPS instruments provided adequate spatial resolution
      (typically about 2-3 m outdoors and 4-5 m indoors) to locate subjects within
      distinct microenvironments and distinguish a variety of human activities.
      Reception experiments showed that location could be tracked outside, proximal to
      buildings, and inside some buildings. Specific location information could
      identify movement in a single room inside a home, on a playground, or along a
      fence line. The instrument, worn in a vest or in bib overalls, was accepted by
      children and parents. Durability of the wiring was improved early in the study to
      correct breakage problems. The use of GPS technology offers a new level of
      accuracy for direct quantification of time-location activity patterns in exposure
      assessment studies.

PMID- 12515690
TI  - Predicting children's short-term exposure to pesticides: results of a
      questionnaire screening approach.
AB  - The ability of questionnaires to predict children's exposure to pesticides was
      examined as part of the Minnesota Children's Pesticide Exposure Study (MNCPES).
      The MNCPES focused on a probability sample of 102 children between the ages of 3
      and 13 years living in either urban (Minneapolis and St. Paul, MN) or nonurban
      (Rice and Goodhue Counties in Minnesota) households. Samples were collected in a
      variety of relevant media (air, food, beverages, tap water, house dust, soil,
      urine), and chemical analyses emphasized three organophosphate insecticides
      (chlorpyrifos, diazinon, malathion) and a herbicide (atrazine). Results indicate
      that the residential pesticide-use questions and overall screening approach used
      in the MNCPES were ineffective for identifying and oversampling
      children/households with higher levels of individual target pesticides.

PMID- 12515691
TI  - Temporal trends in orchidopexy, Great Britain, 1992-1998.
AB  - Concern has been expressed in recent years about worsening male reproductive
      health, possibly mediated by increasing exposures to environmental endocrine
      disrupting agents. Trends suggested large increases in cryptorchidism in Britain
      and the United States between the 1950s and 1980s, although published data on
      recent trends have been scarce. We examined numbers of orchidopexy procedures, as
      a marker for cryptorchidism, using routine hospital admission data for England,
      Wales, and Scotland for fiscal years 1992-1993 through 1998-1999. Annual trends
      in orchidopexy rates were analyzed by age, in-patient admission versus day case,
      and geographical region. Orchidopexy rates were also obtained from the General
      Practice Research Database (GPRD) for England to cross-validate the hospital
      admissions data. Orchidopexy rates for boys 0-14 years old fell by 33% (from 23.5
      to 15.8 per 10,000 population) between 1992 and 1998, with the steepest decline
      (50%) in 5-9-year-olds. The decreasing trend for 0-14-year-olds was evident in
      every region in England, in Wales, and in Scotland. Rates remained stable for men
      15 or more years old, at 0.7 per 10,000. There was a marked shift from in-patient
      to day-case procedures. Rates from the GPRD showed a similar downward trend to
      the hospital data. Our findings could represent either an underlying decrease in
      the frequency of undescended testis or a fairly dramatic improvement in the
      diagnosis of cryptorchidism--resulting in fewer orchidopexies performed for
      retractile testis--in Great Britain during the 1990s, or both. Either way, our
      findings do not support the postulate of a recent worsening of male reproductive
      health of the scale suggested by some recent commentators on the endocrine
      disruptor hypothesis.

PMID- 12515692
TI  - The prooxidant state and psychologic stress.

PMID- 12515694
TI  - Neuropsychologic testing versus visual contrast sensitivity in diagnosing PEAS.

PMID- 12515696
TI  - New thyroid theory: how maternal hormone affects developing brains.

PMID- 12515697
TI  - Sex matters: exploring differences in responses to exposures.

PMID- 12515698
TI  - The quest for fire: hazards of a daily struggle.

PMID- 12515699
TI  - Speaking up: women's voices in environmental decision making.

PMID- 12515700
TI  - Making the best of biomass: hydrogen for fuel cells.

PMID- 12515702
TI  - CT simulation for radiotherapy treatment planning.
AB  - The present status of CT simulation (CT sim) hardware, software and practice is
      reviewed, particularly with regard to the changes that have taken place over the
      last 5 years. The latest technology is discussed together with some recently
      developed techniques. The article concludes with a discussion of virtual
      simulation vs physical (conventional) simulation; in particular there is a review
      of the changes that have been made to the "Disadvantages table" presented by
      Conway and Robinson [1], which now make CT sim an attractive system for any
      radiotherapy department.

PMID- 12515703
TI  - The ability of lymphoscintigraphy to direct sentinel node biopsy in the
      clinically N0 neck for patients with head and neck squamous cell carcinoma.
AB  - This study aimed to evaluate the ability of lymphoscintigraphy (LSG) to direct
      sentinel node biopsy (SNB) in the identification of occult metastases in the
      clinically N0 neck for patients with head and neck squamous cell carcinoma
      (HNSCC). 57 clinically N0 neck sides in 48 patients were assessed using the
      triple diagnostic approach of pre-operative LSG, intra-operative use of a gamma
      probe and blue dye. SNB was performed after radiocolloid and blue dye injection.
      Pre-operative LSG and the intra-operative use of a gamma probe identified
      radioactive sentinel nodes, and visualization of blue stained lymphatics
      identified blue sentinel nodes. 104 sentinel nodes were harvested from 43
      patients. The identification rate was 90% (43 of 48). Of the 104 nodes harvested,
      17 of 62 (27%) nodes identified as both radioactive and blue were positive for
      occult metastases compared with 5 of 42 (12%) nodes identified as hot or blue
      only (p<0.05). Sentinel nodes were identified in 39 of 48 (81%) patients using
      LSG. Of 39 patients in whom sentinel nodes were identified using LSG, 37 of 39
      (95%) had radioactive sentinel nodes harvested intra-operatively. In patients who
      had no sentinel nodes identified on LSG, 4 of 9 (44%) had radioactive sentinel
      nodes harvested intra-operatively. This difference was statistically significant
      using the t-test (p<0.05). LSG directs SNB and is essential in the identification
      of occult metastases within the clinically N0 neck for patients with HNSCC.

PMID- 12515704
TI  - Early in vivo detection of metabolic response: a pilot study of 1H MR
      spectroscopy in extracranial lymphoma and germ cell tumours.
AB  - Monitoring therapeutic efficacy is essential in oncological practice. We have
      investigated the feasibility of using proton (1)H MR spectroscopy (MRS),
      localized to malignant lymphoma and germ cell lesions outside the cranial cavity,
      to monitor tumour metabolism in vivo during chemotherapy treatment. (1)H single
      voxel MRS, (stimulated echo acquisition mode, repetition time/echo time=2000/20
      ms) was performed prior to treatment in patients with lymphoma or germ cell
      tumours, and during the first cycle of chemotherapy. Patient response was
      assessed by independent clinical follow-up at a median of 57 days (range 44-93
      days) post-treatment. All 12 non-cystic lesions scanned showed a signal assigned
      to choline-containing metabolites (tCho); 9 were scanned both pre- and post
      treatment. Changes in the tCho:water ratio following treatment were found to
      predict subsequent patient response. In seven of these nine patients, the
      tCho:water ratio decreased in the first post-treatment scan, and all subsequently
      achieved a partial response to treatment. In the remaining two patients, both of
      whom progressed on treatment, the tCho:water ratio did not change significantly.
      Normalized to pre-treatment values, the non-responder group values (1.07 and
      0.97) were clearly distinct from the responder group, whose values ranged from
      0.43 to below detection level. To our knowledge, this is the first report of (1)H
      MR spectra from these tumour types and sites. These preliminary results indicate
      that metabolite signals can be detected using (1)H MRS in these tumour types and
      locations, as has already been established in the brain, breast and prostate.
      Moreover, the differential changes observed in the tCho region of the spectrum
      suggest that (1)H MRS could provide an early and sensitive indicator of metabolic
      response to chemotherapy.

PMID- 12515705
TI  - Dose-position and dose-volume histogram analysis of standard wedged and intensity
      modulated treatments in breast radiotherapy.
AB  - The aim of this work was to evaluate the positional distribution of dose in a
      concise manner and to analyse dose-histogram results in tangential breast
      radiotherapy in 300 patients, randomized to standard wedged or intensity
      modulated radiotherapy (IMRT), for future correlation with clinical outcome data.
      A simple method for analysing the dose-position relationship in the treatment
      volume was used to compare the spatial distribution of dose in patients. The
      breast was divided into equal thirds (upper, middle and lower) and dose was
      assessed using three dose bands; 95-105%, >105-110% and >110% of the prescription
      dose. The effect of using IMRT on the dosimetry was assessed from dose-volume
      histogram data using the following parameters: percentage of the target volume
      receiving a dose less than 95%, greater than 105%, either less than 95% or
      greater than 105% of that prescribed; the mean dose; and the maximum dose. Doses
      greater than 105% were predominantly in the upper and lower regions of the breast
      in the standard wedged treatment. 96% of these patients received doses greater
      than 105% in the upper region of the breast and 70% received doses greater than
      105% in the lower breast. Only 4% of patients allocated IMRT received doses
      greater than 105% in either region. Analysis of dose-volume histogram data showed
      that IMRT reduced the volume receiving a dose greater than 105% by a mean of
      10.7% (p= or <0.001); the mean change in the volume receiving a dose less than
      95% was 0.2% (p=0.63). Average mean plan dose was 101.6% for standard treatment
      and 99.6% for IMRT (p<0.001 for each compared with 100.0% ideal). The mean value
      of maximum dose was reduced from 111% to 106% in the group of patients randomized
      to IMRT. A simple method for describing the relationship between dose and
      position in the breast, which is helpful for the effective correlation of
      dosimetry and clinical effects, is reported. Further, application of IMRT to the
      tangential field irradiation of the breast has been demonstrated to reduce high
      dose regions in both volume and dose level without compromising either minimum
      dose coverage or mean dose delivered to the breast.

PMID- 12515706
TI  - In vivo estimation of midline dose maps by transit dosimetry in head and neck
      radiotherapy.
AB  - The aim of the present study is to compare the calculated midline dose map with
      the in vivo measured midline dose map, using portal detectors in conjunction with
      a pair of diodes. Measurements were performed in 10 patients treated for
      head/neck cancer and irradiated with lateral opposed 6 MV X-ray beams. The
      relative exit dose map, derived from transmission dose data of a portal film
      combined with the absolute entrance/exit dose measured by the diodes, can be used
      to derive the corresponding midline dose map by applying appropriate algorithms.
      Midplane dose values were estimated in eight relevant anatomic positions and
      compared with the corresponding calculated values with our three-dimensional (3D)
      treatment planning system using two-dimensional (2D) (Batho) and 3D (ETAR)
      inhomogeneity correction algorithms. In vivo estimated midplane doses agree
      within +/-3.5% relative to treatment planning calculations in 89 of 116
      measurements points, with only 4 of 116 points outside +/-5%. A variation between
      measured and calculated dose can be found according to anatomical location. For
      air inhomogeneity, mean deviations were +2.2% (1 standard deviation (SD)
      approximately 1.7%) for both Batho and ETAR algorithms; for bone structures, mean
      deviations were approximately -0.6% (1 SD approximately 2.7%) for both
      algorithms. The worst agreement was found in the anterior neck where the mean
      deviation between measured and calculated midline dose was +3.1% (1 SD=1.4%) and
      +3.4% (1 SD= 2%) using Batho and ETAR, respectively. Sufficiently accurate 2D
      midplane dose maps may be simply obtained in vivo in the irradiation of head/neck
      cancer by using a portal detector in combination with a pair of diodes, in order
      to verify the dose actually delivered during treatment.

PMID- 12515707
TI  - No radiation protection reasons for restrictions on 14C urea breath tests in
      children.
AB  - Traditional (14)C urea breath tests are normally not used for younger children
      because the radiation exposure is unknown. High sensitivity accelerator mass
      spectrometry and an ultra-low amount (440 Bq) of (14)C urea were therefore used
      both to diagnose Helicobacter pylori (HP) infection in seven children, aged 3-6
      years, and to make radiation dose estimates. The activity used was 125 times
      lower than the amount normally used for older children and 250 times lower than
      that used for adults. Results were compared with previously reported biokinetic
      and dosimetric data for adults and older children aged 7-14 years. (14)C activity
      concentrations in urine and exhaled air per unit administered activity for
      younger children (3-6 years) correspond well with those for older children (7-14
      years). For a child aged 3-6 years who is HP negative, the urinary bladder wall
      receives the highest absorbed dose, 0.3 mGy MBq(-1). The effective dose is 0.1
      mSv MBq(-1) for the 3-year-old child and 0.07 mSv MBq(-1) for the 6-year-old
      child. For two children, the 10 min and 20 min post-(14)C administration samples
      of exhaled air showed a significantly higher amount of (14)C activity than for
      the rest of the children, that is 6% and 19% of administered activity exhaled per
      hour compared with 0.3-0.9% (mean 0.5%) of administered activity exhaled per hour
      indicating that these two children that is were HP positive. For a 3-year-old HP
      positive child, absorbed dose to the urinary bladder wall was 0.3 mGy MBq(-1) and
      effective dose per unit of administered activity was 0.4 mSv MBq(-1). Using 55
      kBq, which is a normal amount for older children when liquid scintillation
      counters are used for measurement, the effective dose will be approximately 6
      micro Sv to a 3-year-old HP negative child and 20 microSv to a HP positive child.
      Thus there is no reason for restrictions on performing a normal (14)C urea breath
      test, even on young children.

PMID- 12515708
TI  - Case report: gastroduodenal intussusception of a gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumours (GISTs), previously termed leiomyomas and
      leiomyosarcomas are relatively common tumours of the gastrointestinal tract, most
      commonly found in the stomach. Most GISTs are asymptomatic but may cause
      abdominal pain or bleeding from ulceration of the overlying mucosa. A rare case
      of gastroduodenal intussusception of a large gastric stromal tumour, which
      presented with intermittent abdominal pain and gastric outlet obstruction, is
      reported. Pre-operative diagnosis was made on abdominal CT and confirmed at
      laparotomy. Pre-operative diagnostic difficulties and management are discussed.

PMID- 12515709
TI  - Case report: bilateral vocal cord paralysis caused by cervical spinal
      osteophytes.
AB  - Thyroid and cervical surgery, tracheal intubation, trauma and neurodegenerative
      and neuromuscular diseases may cause bilateral vocal cord paralysis. There are
      only a few reported cases of bilateral cord paralysis associated with cervical
      hyperostosis in the English literature. We report the MR and CT findings of a
      case of bilateral vocal cord paralysis caused by cervical spinal osteophytes
      compressing the recurrent laryngeal nerves.

PMID- 12515710
TI  - Pictorial review: various causes of hepatic capsular retraction: CT and MR
      findings.
AB  - Hepatic capsular retraction adjacent to hepatic tumour is rare, although this
      finding has been described in a variety of malignant tumours and haemangioma. The
      authors have seen various causes of hepatic capsular retraction associated with
      hepatic tumours, including a variety of malignant tumours, haemangioma and post
      treatment of malignant tumours, as well as cases not associated with a hepatic
      tumour, including confluent hepatic fibrosis, oriental cholangiohepatitis and
      bile duct necrosis. Furthermore, causes of pseudoretraction of the hepatic
      capsule, including accessory fissure and normal liver parenchyma between the
      protruded masses, are described.

PMID- 12515711
TI  - Case of the month: a pain in the neck.

PMID- 12515713
TI  - Re: Communication of doubt and uncertainty in radiological reports.

PMID- 12515714
TI  - Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in
      diffuse large B-cell lymphoma.
AB  - The BCL6 proto-oncogene encodes a transcriptional repressor whose expression is
      deregulated by chromosomal translocations in approximately 40% of diffuse large B
      cell lymphomas (DLBCLs). The BCL6 regulatory sequences are also targeted by
      somatic hypermutation in germinal center (GC) B cells and in a fraction of all GC
      derived lymphomas. However, the functional consequences of these mutations are
      unknown. Here we report that a subset of mutations specifically associated with
      DLBCL causes deregulated BCL6 transcription. These mutations affect 2 adjacent
      BCL6 binding sites located within the first noncoding exon of the gene, and they
      prevent BCL6 from binding its own promoter, thereby disrupting its negative
      autoregulatory circuit. These alterations were found in approximately 16% of
      DLBCLs devoid of chromosomal translocations involving the BCL6 locus, but they
      were not found in normal GC B cells. This study establishes a novel mechanism for
      BCL6 deregulation and reveals a broader involvement of this gene in DLBCL
      pathogenesis.

PMID- 12515715
TI  - AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe
      hemophilia B.
AB  - Hemophilia B is an X-linked coagulopathy caused by absence of functional
      coagulation factor IX (F.IX). Previously, we established an experimental basis
      for gene transfer as a method of treating the disease in mice and hemophilic dogs
      through intramuscular injection of a recombinant adeno-associated viral (rAAV)
      vector expressing F.IX. In this study we investigated the safety of this approach
      in patients with hemophilia B. In an open-label dose-escalation study, adult men
      with severe hemophilia B (F.IX < 1%) due to a missense mutation were injected at
      multiple intramuscular sites with an rAAV vector. At doses ranging from 2 x
      10(11) vector genomes (vg)/kg to 1.8 x 10(12) vg/kg, there was no evidence of
      local or systemic toxicity up to 40 months after injection. Muscle biopsies of
      injection sites performed 2 to 10 months after vector administration confirmed
      gene transfer as evidenced by Southern blot and transgene expression as evidenced
      by immunohistochemical staining. Pre-existing high-titer antibodies to AAV did
      not prevent gene transfer or expression. Despite strong evidence for gene
      transfer and expression, circulating levels of F.IX were in all cases less than
      2% and most were less than 1%. Although more extensive transduction of muscle
      fibers will be required to develop a therapy that reliably raises circulating
      levels to more than 1% in all subjects, these results of the first parenteral
      administration of rAAV demonstrate that administration of AAV vector by the
      intramuscular route is safe at the doses tested and effects gene transfer and
      expression in humans in a manner similar to that seen in animals.

PMID- 12515716
TI  - IQGAP2 functions as a GTP-dependent effector protein in thrombin-induced platelet
      cytoskeletal reorganization.
AB  - Human blood platelets are anucleate cells whose response to extracellular stimuli
      results in actin cytoskeleton rearrangements, thereby providing the critical
      initial step in the regulation of hemostasis. The serine protease alpha-thrombin,
      known to activate platelets by cleavage of a family of protease-activated
      receptors (PARs), is the most potent physiologic activator of human platelets,
      though downstream effector proteins uniquely linked to platelet cytoskeletal
      actin polymerization remain largely uncharacterized. The gene encoding the
      putative rac1/cdc42 effector protein IQGAP2 was identified within the PAR gene
      cluster at 5q13, flanked telomeric by PAR1 and encompassing PAR3.
      Immunofluorescence microscopy demonstrated IQGAP2 expression in filopodial
      extensions of activated platelets and colocalized with F-actin in lamellipodia
      and filopodia of IQGAP2-transfected COS1 cells. Platelet activation by alpha
      thrombin, but not saturating concentrations of fibrillar collagen or adenosine 5'
      diphosphate, uniquely assemble an IQGAP2/arp2/3-actin cytoplasmic complex, an
      association regulated by guanosine triphosphate rac1 ([GTP]rac1) but not by
      [GTP]cdc42. Likewise, only thrombin-activated platelets resulted in rapid
      translocation of IQGAP2 to the platelet cytoskeleton. These observations identify
      a physiologic scaffolding function for IQGAP2 and establish the presence of a
      functional genomic unit in humans uniquely evolved to regulate thrombin-induced
      platelet cytoskeletal actin reorganization.

PMID- 12515717
TI  - Cobalamin deficiency with and without neurologic abnormalities: differences in
      homocysteine and methionine metabolism.
AB  - The unknown biochemical basis for neurologic dysfunction in cobalamin deficiency
      and the frequent divergence between neurologic and hematologic manifestations led
      us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum
      levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet),
      cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only
      levels of tHcy and cysteine were increased and only GSH was decreased in
      cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet
      correlated only with methionine levels (P =.015) and cysteine only with cys-gly
      (P =.007) in healthy subjects, but in cobalamin-deficient patients AdoMet
      correlated instead with cysteine, cys-gly, and folate levels only (P =.008, P
      =.03, and P =.03, respectively). Significant differences appeared in clinically
      subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects
      had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6
      nM), cysteine (462 versus 325 microM), and cys-gly (85.0 versus 54.7 microM) than
      the 11 neurologically unaffected patients. Cobalamin therapy restored all
      metabolic changes to normal. The results indicate that changes in several
      metabolic pathways differ in patients with and without neurologic dysfunction.
      Cysteine levels were the most significant predictors of neurologic dysfunction,
      but it is unclear if they are direct or indirect indicators of neurotoxicity. The
      higher AdoMet levels in neurologically affected patients may result from
      inhibition of glycine N-methyltransferase by those patients' higher folate
      levels. The origin of the folate differences is unclear and possibly varied. Low
      AdoMet and GSH levels were independent predictors of anemia.

PMID- 12515718
TI  - Enhancement of ATRA-induced cell differentiation by inhibition of calcium
      accumulation into the endoplasmic reticulum: cross-talk between RAR alpha and
      calcium-dependent signaling.
AB  - Sarco-endoplasmic reticulum calcium ATPase (SERCA) enzymes control calcium
      induced cellular activation by accumulating calcium from the cytosol into the
      endoplasmic reticulum (ER). To better understand the role of SERCA proteins and
      cellular calcium homeostasis in all-trans retinoic acid (ATRA)-induced
      differentiation, we investigated the effect of pharmacologic inhibition of SERCA
      dependent calcium uptake into the ER on ATRA-induced differentiation of the HL-60
      myelogenous and the NB4 promyelocytic cell lines. SERCA inhibitors di-tert-butyl
      benzohydroquinone (tBHQ), thapsigargin, and cyclopiazonic acid significantly
      enhanced the induction of nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase activity and CD11b marker expression induced by suboptimal concentrations
      of ATRA (50 nM) in both cell lines. Analysis of cellular calcium homeostasis
      revealed that a 60% mobilization of the total SERCA-dependent intracellular
      calcium pool was necessary to obtain enhancement of ATRA-dependent
      differentiation by tBHQ. Moreover, after 3 days of ATRA treatment in combination
      with tBHQ, NB4 cells showed a significantly decreased calcium mobilization
      compared with treatments with tBHQ or ATRA alone, suggesting that enhanced
      differentiation and calcium mobilization are causally related. Interestingly,
      several ATRA-resistant NB4-derived cell lines were partially responsive to the
      differentiation-inducing effect of the combination of the 2 drugs. In addition,
      we found that retinoic acid receptor alpha (RAR alpha) and PML-RAR alpha proteins
      are protected from ATRA-induced proteolytic degradation by SERCA inhibition,
      indicating that cellular calcium homeostasis may interact with signaling systems
      involved in the control of ATRA-dependent transcriptional activity. By linking
      calcium to ATRA-dependent signaling, our data open new avenues in the
      understanding of the mechanisms of differentiation-induction therapy of leukemia.

PMID- 12515719
TI  - Immunoglobulin light chain variable (V) region genes influence clinical
      presentation and outcome in light chain-associated amyloidosis (AL).
AB  - Light chain-associated amyloidosis (AL) is a plasma cell dyscrasia in which the
      secreted monoclonal immunoglobulin (Ig) light chains form amyloid fibrils. There
      is considerable heterogeneity in clinical presentation, and prognosis of the
      disease relates to the severity of organ dysfunction induced by amyloid deposits.
      The mechanisms by which the amyloid fibrils are deposited as well as the
      predilection for specific organ sites have not been clearly elucidated. This
      study characterizes the repertoire of immunoglobulin light chain variable genes
      used by the clonal B cell in AL amyloid patients, and the association of light
      chain variable region (VL) genes with clinical presentation and outcome is
      assessed in 58 (32 lambda and 26 kappa) patients. A preferential use of VL germ
      line genes was noted for both AL kappa and lambda patients. There was a
      significant correlation between the use of the Vlambda VI germ-line donor, 6a,
      and renal involvement as well as the Vlambda III gene, 3r, with soft-tissue AL.
      The use of a biased VL gene repertoire also correlated with clinical outcome,
      revealing important trends for predicting prognosis. The use of Vlambda II germ
      line genes was associated with cardiac amyloidosis and affected survival
      adversely. The presence of multiple myeloma also correlated with a poor
      prognosis. The presence of renal disease, on the other hand, was associated with
      improved survival. Therefore, identification of the clonal VL gene in AL has
      important implications in determining clinical outcome.

PMID- 12515720
TI  - Downstream effectors of oncogenic ras in multiple myeloma cells.
AB  - Ectopic expression of mutated K-ras or N-ras in the interleukin 6 (IL-6)
      dependent ANBL6 multiple myeloma cell line induces cytokine-independent growth.
      To investigate the signaling pathways activated by oncogenic ras that may
      stimulate IL-6-independent growth, we compared ANBL6 cells stably transfected
      with mutated K or N-ras genes with wild-type ras-expressing control cells
      identically transfected with an empty vector. Upon depletion of IL-6, both
      mutated ras-containing myeloma lines demonstrated constitutive activation of
      mitogen-activated extracellular kinase 2(MEK)/extracellular signal-regulated
      kinase (ERK), phosphatidylinositol-3 kinase (PI3-kinase)/AKT, mammalian target of
      rapamycin (mTOR)/p70S6-kinase, and nuclear factor kappa B (NF-kappa B) pathways.
      In contrast, signal transducer and activator of transcription-3 (STAT-3) was not
      constitutively tyrosine phosphorylated in mutant ras-expressing cells. We used
      several maneuvers in attempts to selectively target these constitutively active
      pathways. The mTOR inhibitors rapamycin and CCI-779, the PI3-kinase inhibitor
      LY294002, and the MEK inhibitor PD98059 all significantly curtailed growth of
      mutant ras-containing cells. Farnesyl transferase inhibitors, used to target ras
      itself, had modest effects only against mutant N-ras-containing cells. Growth of
      mutant N-ras-containing myeloma cells was also inhibited by acute expression of
      the IKB superrepressor gene, which abrogated NF-kappa B activation. These results
      indicate that several pathways contributing to stimulation of cytokine
      independent growth are activated downstream of oncogenic ras in myeloma cells.
      They also suggest that therapeutic strategies that target these pathways may be
      particularly efficacious in patients whose myeloma clones contain ras mutations.

PMID- 12515721
TI  - Clonal expansion of CD8+ BV8 T lymphocytes in bone marrow characterizes thymoma
      associated B lymphopenia.
AB  - A subgroup of thymoma patients is affected by severe immunodeficiency clinically
      resembling an HIV infection (Good syndrome). These individuals are characterized
      by B lymphopenia with B-lymphopoiesis deficiency. To investigate the pathogenesis
      of this unique condition, we studied the T-cell repertoire in blood and bone
      marrow samples by heterogeneity length analysis of CDR3 beta variable regions of
      the T-cell receptor (spectratyping). While no alterations were found in the
      peripheral blood, we detected an oligoclonal population of beta variable 8 (BV8)
      CD8(+) T cells in 5 of 5 bone marrow samples. No lymphocyte expansions were found
      in the bone marrow of 2 thymoma patients with normal B-cell counts, 2 healthy
      donors, and 3 patients with diseases unrelated to thymoma. These data suggest
      that an immune response toward an unknown antigen is taking place in the bone
      marrow of B-lymphopenic thymoma patients. We propose that BV8 CD8(+) T cells may
      play a role in the pathogenesis of this immunodeficiency syndrome.

PMID- 12515722
TI  - A nonsecreted variant of interleukin-4 is associated with apoptosis: implication
      for the T helper-2 polarization in HIV infection.
AB  - We report the detection of an interleukin-4 (IL-4) variant whose expression is
      tightly associated with deprivation apoptosis. It is detected with the 8D4 anti
      IL-4 monoclonal antibody (mAb) not only in T helper-2 (Th2) but also in Th1
      clones, and primary T cells, and it is a nonsecreted molecule. It is not
      expressed during primary necrosis. Our data suggest that de novo IL-4
      transcription of an alternative IL-4 mRNA (IL-4 delta(13)) is induced during
      deprivation apoptosis. In HIV-infected patients, increased expression of IL-4 in
      T cells is highly correlated to increased apoptosis, restricted to 8D4 reactivity
      (r(2) = 0.84 between % 8D4-8(+) and % 7- amino-actinomycin D-positive [7-AAD(+)]
      peripheral T cells, P <.0001), and associated with disease progression. The
      particular reactivity of apoptotic T cells to 8D4 mAb may explain some
      discordances among studies analyzing the Th1/Th2 balance in HIV infection and
      questions the function of this intracellular type 2 signal.

PMID- 12515723
TI  - Cell death induced by granzyme C.
AB  - Although the functions of granzymes A and B have been defined, the functions of
      the other highly expressed granzymes (Gzms) of murine cytotoxic lymphocytes (C,
      D, and F) have not yet been evaluated. In this report, we describe the ability of
      murine GzmC (which is most closely related to human granzyme H) to cause cell
      death. The induction of death requires its protease activity and is characterized
      by the rapid externalization of phosphatidylserine, nuclear condensation and
      collapse, and single-stranded DNA nicking. The kinetics of these events are
      similar to those caused by granzyme B, and its potency (defined on a molar basis)
      is also equivalent. The induction of death did not involve the activation of
      caspases, the cleavage of BID, or the activation of the CAD nuclease. However,
      granzyme C did cause rapid mitochondrial swelling and depolarization in intact
      cells or in isolated mitochondria, and this mitochondrial damage was not
      prevented by cyclosporin A pretreatment. These results suggest that granzyme C
      rapidly induces target cell death by attacking nuclear and mitochondrial targets
      and that these targets are distinct from those used by granzyme B to cause
      classical apoptosis.

PMID- 12515724
TI  - Discrimination of polycythemias and thrombocytoses by novel, simple, accurate
      clonality assays and comparison with PRV-1 expression and BFU-E response to
      erythropoietin.
AB  - Essential thrombocythemia (ET) and polycythemia vera (PV) are clonal
      myeloproliferative disorders that are often difficult to distinguish from other
      causes of elevated blood cell counts. Assays that could reliably detect clonal
      hematopoiesis would therefore be extremely valuable for diagnosis. We previously
      reported 3 X-chromosome transcription-based clonality assays (TCAs) involving the
      G6PD, IDS, and MPP1 genes, which together were informative in about 65% of female
      subjects. To increase our ability to detect clonality, we developed simple TCA
      for detecting the transcripts of 2 additional X-chromosome genes: Bruton tyrosine
      kinase (BTK) and 4-and-a-half LIM domain 1 (FHL1). The combination of TCA
      established the presence or absence of clonal hematopoiesis in about 90% of
      female subjects. We show that both genes are subject to X-chromosome inactivation
      and are polymorphic in all major US ethnic groups. The 5 TCAs were used to
      examine clonality in 46 female patients along with assays for erythropoietin
      independent erythroid colonies (EECs) and granulocyte PRV-1 mRNA levels to
      discriminate polycythemias and thrombocytoses. Of these, all 19 patients with
      familial polycythemia or thrombocytosis had polyclonal hematopoiesis, whereas 22
      of 26 patients with clinical evidence of myeloproliferative disorder and 1
      patient with clinically obscure polycythemia were clonal. Interestingly,
      interferon alpha therapy in 2 patients with PV was associated with reversion of
      clonal to polyclonal hematopoiesis. EECs were observed in 14 of 14 patients with
      PV and 4 of 12 with ET, and increased granulocyte PRV-1 mRNA levels were found in
      9 of 13 patients with PV and 2 of 12 with ET. Thus, these novel clonality assays
      are useful in the diagnosis and follow-up of polycythemic conditions and
      disorders with increased platelet levels.

PMID- 12515725
TI  - Active suppression of allogeneic proliferative responses by dendritic cells after
      induction of long-term allograft survival by CTLA4Ig.
AB  - Costimulatory blockade using cytotoxic T lymphocyte-associated antigen 4
      immunoglobulin (CTLA4Ig) efficiently down-regulates immune responses in animal
      models and is currently used in autoimmune and transplantation clinical trials,
      but the precise cellular and molecular mechanisms involved remain unclear. Rats
      that received allogeneic heart transplants and were treated with adenoviruses
      coding for CTLA4Ig show long-term allograft survival. The immune mechanisms
      regulating induction of long-term allograft acceptance were analyzed in
      splenocytes using mixed leukocyte reactions (MLRs). MLRs of splenocytes but not
      purified T cells from CTLA4Ig-treated rats showed higher than 75% inhibition
      compared with controls. Splenocytes from CTLA4Ig-treated rats inhibited
      proliferation of naive and allogeneically primed splenocytes or T cells. MLR
      suppression was dependent on soluble secreted product(s). Production of soluble
      inhibitory product(s) was triggered by a donor antigen-specific stimulation and
      inhibited proliferation in an antigen-nonspecific manner. CTLA4Ig levels in the
      culture supernatant were undetectable and neither interleukin-10 (IL-10),
      transforming growth factor beta 1 (TGF beta 1), IL-4, nor IL-13 were responsible
      for suppression of MLRs. Inhibition of nitric oxide (NO) production or addition
      of IL-2 could not restore proliferation independently, but the combined treatment
      synergistically induced proliferation comparable with controls. Stimulation of
      APCs using tumor necrosis factor (TNF)-related activation-induced cytokine
      (TRANCE) or CD40L and addition of IL-2 normalized MLRs of CTLA4Ig-treated
      splenocytes. Finally, dendritic cells (DCs), but not T cells, from CTLA4Ig
      treated rats inhibited naive MLRs. Altogether, these results provide evidence
      that after in vivo CTLA4Ig treatment, splenocytes, and in particular DCs, can
      inhibit alloantigen-induced proliferative responses through secretion of
      inhibitory products, thus promoting alloantigen-specific tolerance in vivo.

PMID- 12515726
TI  - Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy
      like Burkitt lymphoma cells.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for
      clinical depression and a range of anxiety-related disorders. They are well
      tolerated over extended periods with more than 50 million people worldwide
      benefiting from their use. Here we show that 3 structurally distinct SSRIs-
      fluoxetine, paroxetine, and citalopram--act directly on Burkitt lymphoma (BL)
      cells to trigger rapid and extensive programmed cell death. SSRIs unexpectedly
      stimulated calcium flux, tyrosine phosphorylation, and down-regulation of the c
      myc and nm23 genes in Burkitt lymphoma cells remaining faithful to the biopsy
      phenotype. Resultant SSRI-induced apoptosis was preceded by caspase activation,
      poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, DNA fragmentation, a loss of
      mitochondrial membrane potential, and the externalization of phosphatidylserine,
      and reversed by the overexpression of bcl-2. Normal peripheral blood mononuclear
      cells and tonsil B cells, whether resting or stimulated into cycle, were largely
      resistant to SSRI-induced death as were 5 non-BL lymphoid cell lines tested. We
      discuss these findings within the context of whether the SSRI class of
      antidepressants could find future application as potential therapeutics for the
      highly aggressive and-because of its association with AIDS-increasingly more
      common Burkitt lymphoma.

PMID- 12515727
TI  - A model of APL with FLT3 mutation is responsive to retinoic acid and a receptor
      tyrosine kinase inhibitor, SU11657.
AB  - The PML-RAR alpha fusion protein is central to the pathogenesis of acute
      promyelocytic leukemia (APL). Expression of this protein in transgenic mice
      initiates myeloid leukemias with features of human APL, but only after a long
      latency (8.5 months in MRP8 PML-RARA mice). Thus, additional changes contribute
      to leukemic transformation. Activating mutations of the FLT3 receptor tyrosine
      kinase are common in human acute myeloid leukemias and are frequent in human APL.
      To assess how activating mutations of FLT3 contribute to APL pathogenesis and
      impact therapy, we used retroviral transduction to introduce an activated allele
      of FLT3 into control and MRP8 PML-RARA transgenic bone marrow. Activated FLT3
      cooperated with PML-RAR alpha to induce leukemias in 62 to 299 days (median
      latency, 105 days). In contrast to the leukemias that arose spontaneously in MRP8
      PML-RARA mice, the activated FLT3/PML-RAR alpha leukemias were characterized by
      leukocytosis, similar to human APL with FLT3 mutations. Cytogenetic analysis
      revealed clonal karyotypic abnormalities, which may contribute to pathogenesis or
      progression. SU11657, a selective, oral, multitargeted tyrosine kinase inhibitor
      that targets FLT3, cooperated with all-trans retinoic acid to rapidly cause
      regression of leukemia. Our results suggest that the acquisition of FLT3
      mutations by cells with a pre-existing t(15;17) is a frequent pathway to the
      development of APL. Our findings also indicate that APL patients with FLT3
      mutations may benefit from combination therapy with all-trans retinoic acid plus
      an FLT3 inhibitor.

PMID- 12515728
TI  - Prenatal and postnatal myeloid cells demonstrate stepwise progression in the
      pathogenesis of MLL fusion gene leukemia.
AB  - The steps to leukemia following an in utero fusion of MLL (HRX, ALL-1) to a
      partner gene in humans are not known. Introduction of the Mll-AF9 fusion gene
      into embryonic stem cells results in leukemia in mice with cell-type specificity
      similar to humans. In this study we used myeloid colony assays,
      immunophenotyping, and transplantation to evaluate myelopoiesis in Mll-AF9 mice.
      Colony assays demonstrated that both prenatal and postnatal Mll-AF9 tissues have
      significantly increased numbers of CD11b(+)/CD117(+)/Gr-1(+/-) myeloid cells,
      often in compact clusters. The self-renewal capacity of prenatal myeloid
      progenitors was found to decrease following serial replating of colony-forming
      cells. In contrast, early postnatal myeloid progenitors increased following
      replating; however, the enhanced self-renewal of early postnatal myeloid
      progenitor cells was limited and did not result in long-term cell lines or
      leukemia in vivo. Unlimited replating, long-term CD11b/Gr-1(+) myeloid cell
      lines, and the ability to produce early leukemia in vivo in transplantation
      experiments, were found only in mice with overt leukemia. Prenatal Mll-AF9
      tissues had reduced total (mature and progenitor) CD11b/Gr-1(+) cells compared
      with wild-type tissues. Colony replating, immunophenotyping, and cytochemistry
      suggest that any perturbation of cellular differentiation from the prenatal stage
      onward is partial and largely reversible. We describe a novel informative in
      vitro and in vivo model system that permits study of the stages in the
      pathogenesis of Mll fusion gene leukemia, beginning in prenatal myeloid cells,
      progressing to a second stage in the postnatal period and, finally, resulting in
      overt leukemia in adult animals.

PMID- 12515729
TI  - Regulation of neutrophil and eosinophil secondary granule gene expression by
      transcription factors C/EBP epsilon and PU.1.
AB  - In the bone marrow of C/EBP epsilon(-/-) mice, expression of neutrophil secondary
      and tertiary granule mRNAs is absent for lactoferrin (LF), neutrophil gelatinase
      (NG), murine cathelin-like protein (MCLP), and the cathelin B9; it is severely
      reduced for neutrophil collagenase (NC) and neutrophil gelatinase-associated
      lipocalin (NGAL). In addition, the expression of eosinophil granule genes, major
      basic protein (MBP), and eosinophil peroxidase (EPX) is absent. These mice
      express C/EBP alpha, C/EBP beta, and C/EBP delta in the bone marrow at levels
      similar to those of their wild-type counterparts, suggesting a lack of functional
      redundancy among the family in vivo. Stable inducible expression of C/EBP epsilon
      and C/EBP alpha in the murine fibroblast cell line NIH 3T3 activated expression
      of mRNAs for B9, MCLP, NC, and NGAL but not for LF. In transient transfections of
      C/EBP epsilon and C/EBP alpha, B9 was strongly induced with weaker induction of
      the other genes. C/EBP beta and C/EBP delta proteins weakly induced B9
      expression, but C/EBP delta induced NC expression more efficiently than the other
      C/EBPs. The expression of MBP was inefficiently induced by C/EBP epsilon alone
      and weakly induced with C/EBP epsilon and GATA-1, but the addition of PU.1
      resulted in a striking cooperative induction of MBP in NIH 3T3 cells. Mutation of
      a predicted PU.1 site in the human MBP promoter-luciferase reporter construct
      abrogated the response to PU.1. Gel-shift analysis demonstrated binding of PU.1
      to this site. MBP and EPX mRNAs were absent in a PU.1-null myeloid cell line
      established from the embryonic liver of PU.1(-/-) mice. Restitution of PU.1
      protein expression restored MBP and EPX protein expression. This study
      demonstrates that C/EBP epsilon is essential and sufficient for the expression of
      a particular subset of neutrophil secondary granule genes. Furthermore, it
      indicates the importance of PU.1 in the cooperative activation of eosinophil
      granule genes.

PMID- 12515730
TI  - Sequestration of p27Kip1 protein by cyclin D1 in typical and blastic variants of
      mantle cell lymphoma (MCL): implications for pathogenesis.
AB  - p27 is a cyclin-dependent kinase inhibitor that plays a critical role in
      regulating G(1)/S progression, and whose activity is, in part, regulated through
      interactions with D-type cyclins. Mantle cell lymphoma (MCL) is characterized by
      the t(11;14) translocation resulting in deregulated cyclin D1. We previously
      showed that p27 expression in MCL, as assessed by immunohistochemistry (IHC),
      does not show the usual inverse relationship to proliferate seen in most other
      lymphomas that do not overexpress cyclin D1. This suggested that the normal
      expression or control of p27 activity on cell growth might be altered through
      potential interactions with cyclin D1. Using Western blot and
      coimmunoprecipitation studies, we assessed the interrelationship between cyclin
      D1 and p27 in several cyclin D1(+) cell lines and primary MCL cases. Similar to
      our previous results by IHC, typical MCLs showed lower expression of p27 when
      compared to the more highly proliferative blastic cases or cell lines (mean
      arbitrary units: 58 versus 236 versus 120). Cyclin D1 was expressed at variable
      levels in both typical and blastic MCLs. p27 protein could be consistently
      coimmunoprecipitated with cyclin D1 from both cell lines and cases. Using
      techniques of exhaustive immunoprecipitation, we could demonstrate that most p27
      protein was sequestered into complexes containing cyclin D1. We hypothesize that
      mantle cell lymphomagenesis results not only from direct consequences of
      inappropriate cyclin D1 expression, but also from the ability of overexpressed
      cyclin D1 to buffer physiologic changes in p27 levels, thereby rendering p27
      ineffective as an inhibitor of cellular growth.

PMID- 12515732
TI  - Hormone replacement therapy and heart disease: replacing dogma with data.

PMID- 12515733
TI  - Contemporary management of patent foramen ovale.

PMID- 12515734
TI  - Diets and clinical coronary events: the truth is out there.

PMID- 12515735
TI  - Aspirin alters the cardioprotective effects of the factor XIII Val34Leu
      polymorphism.
AB  - BACKGROUND: The mechanism underlying decreased risk for myocardial infarction in
      carriers of the Leu34 polymorphism of the factor (F) XIII A-subunit is unclear.
      Given that acetylation of fibrinogen by aspirin can alter its clotting properties
      and the presence of fibrin stimulates thrombin-mediated activation of FXIII, we
      have tested the hypothesis that treatment with aspirin differentially modulates
      the influence of the FXIII Val34Leu polymorphism on its activation in vivo.
      METHODS AND RESULTS: The rates of the disappearance of FXIIIA chain and the
      appearance of its activated form (FXIIIAa) in sequential 30-second blood samples
      collected at the site of microvascular injury were compared in 14 healthy
      carriers of the Leu34 allele and 23 Val34 homozygotes both before and after a 7
      day aspirin ingestion (75 mg/d), with the use of quantitative Western blotting.
      The presence of the Leu34 allele was associated with a significant increase in
      the maximum rate of FXIII activation by thrombin. Although the Leu34-positive and
      -negative subjects were similar with respect to aspirin-related impairment of
      thrombin generation, aspirin led to a more pronounced inhibition of the
      activation of FXIII in the Leu34 carriers as compared with the Val34 homozygotes.
      CONCLUSIONS: Inhibition of FXIII activation by aspirin is enhanced in the Leu34
      carriers in vivo, suggesting that these subjects might benefit more than the
      Leu34-negative subjects from the reduction in risk for myocardial infarction with
      low-dose aspirin.

PMID- 12515736
TI  - Pulmonary vein ostium geometry: analysis by magnetic resonance angiography.
AB  - BACKGROUND: During a catheter ablation procedure for selective electrical
      isolation of pulmonary vein (PV) ostia, the size of these ostia is usually
      estimated using fluoroscopic angiography. This measurement may be misleading,
      however, because only the projected supero/inferior ostium diameters can be
      measured. In this study, we analyzed 3-dimensional magnetic resonance
      angiographic (MRA) images to measure the minimal and maximal cross-sectional
      diameter of PV ostia in relation to the diameter that would have been projected
      on fluoroscopic angiograms during a catheter ablation procedure. METHODS AND
      RESULTS: In 42 patients with idiopathic atrial fibrillation who were scheduled
      for selective electrical isolation of PV ostia, the minimal and maximal diameters
      of these ostia were measured from 3-dimensional MRA images. Thereafter, these
      images were oriented in a 45 degrees right or left anterior oblique direction and
      the projected diameter of the PV ostia were measured again. The average ratio
      between maximal and minimal diameter was 1.5+/-0.4 for the left and 1.2+/-0.1 for
      the right pulmonary vein ostia. Because of the orientation and oval shape of
      especially the left pulmonary vein ostia, their minimal diameters were
      significantly smaller than the projected diameters. CONCLUSION: Pulmonary vein
      ostia, especially those at the left, are oval with the short axis oriented
      approximately in the antero/posterior direction. Consequently, PV ostia may
      sometimes be very narrow despite a rather normal appearance on angiographic
      images obtained during a catheter ablation procedure.

PMID- 12515737
TI  - Sirolimus-eluting stent for the treatment of in-stent restenosis: a quantitative
      coronary angiography and three-dimensional intravascular ultrasound study.
AB  - BACKGROUND: We have previously reported the safety and effectiveness of sirolimus
      eluting stents for the treatment of de novo coronary lesions. The present
      investigation explored the potential of this technology to treat in-stent
      restenosis. METHODS AND RESULTS: Twenty-five patients with in-stent restenosis
      were successfully treated with the implantation of 1 or 2 sirolimus-eluting Bx
      VELOCITY stents in Sao Paulo, Brazil. Nine patients received 2 stents (1.4 stents
      per lesion). Angiographic and volumetric intravascular ultrasound (IVUS) images
      were obtained after the procedure and at 4 and 12 months. All vessels were patent
      at the time of 12-month angiography. Angiographic late loss averaged 0.07+/-0.2
      mm in-stent and -0.05+/-0.3 mm in-lesion at 4 months, and 0.36+/-0.46 mm in-stent
      and 0.16+/-0.42 mm in-lesion after 12 months. No patient had in-stent or stent
      margin restenosis at 4 months, and only one patient developed in-stent restenosis
      at 1-year follow-up. Intimal hyperplasia by 3-dimensional IVUS was 0.92+/-1.9
      mm(3) at 4 months and 2.55+/-4.9 mm(3) after 1 year. Percent volume obstruction
      was 0.81+/-1.7% and 1.76+/-3.4% at the 4- and 12-month follow-up, respectively.
      There was no evidence of stent malapposition either acutely or in the follow-up
      IVUS images, and there were no deaths, stent thromboses, or repeat
      revascularizations. CONCLUSION: This study demonstrates the safety and the
      potential utility of sirolimus-eluting Bx VELOCITY stents for the treatment of in
      stent restenosis.

PMID- 12515738
TI  - Effect of cardiac resynchronization on myocardial efficiency and regional
      oxidative metabolism.
AB  - BACKGROUND: Recent studies have demonstrated increased left ventricular
      contractility with cardiac resynchronization therapy (CRT) using
      atriobiventricular stimulation. This study evaluated the effect of CRT on
      myocardial oxidative metabolism and efficiency. METHODS AND RESULTS: Eight
      patients with New York Heart Association functional class III-IV congestive heart
      failure were studied during atrial pacing (control) and atriobiventricular
      stimulation at the same rate. The monoexponential clearance rate of [11C]acetate
      (k(mono)) was measured with positron emission tomography to assess myocardial
      oxidative metabolism in the left and right ventricles (LV and RV, respectively).
      Myocardial efficiency was measured using the work metabolic index (WMI). Stroke
      volume index improved by 10% (P=0.011) with CRT, although both global LV and RV
      k(mono) were unchanged compared with control. Septal k(mono) increased by 15%
      (P=0.04), and the septal/lateral wall k(mono) ratio increased by 22% (P=0.01).
      WMI increased by 13% (P=0.024) with CRT. CONCLUSIONS: CRT improves LV function
      without increasing global LV oxidative metabolism, resulting in improved
      myocardial efficiency. Oxidative metabolism of the interventricular septum
      increases relative to the lateral wall, which suggests successful
      resynchronization.

PMID- 12515739
TI  - Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation:
      a new drug-drug interaction.
AB  - BACKGROUND: We observed that the prodrug clopidogrel was less effective in
      inhibiting platelet aggregation with coadministration of atorvastatin during
      point-of-care platelet function testing. Because atorvastatin is metabolized by
      cytochrome P450 (CYP) 3A4, we hypothesized that clopidogrel might be activated by
      CYP3A4. METHODS AND RESULTS: Platelet aggregation was measured in 44 patients
      undergoing coronary artery stent implantation treated with clopidogrel or
      clopidogrel plus pravastatin or atorvastatin, and in 27 volunteers treated with
      clopidogrel and either erythromycin or troleandomycin, CYP3A4 inhibitors, or
      rifampin, a CYP3A4 inducer. Atorvastatin, but not pravastatin, attenuated the
      antiplatelet activity of clopidogrel in a dose-dependent manner. Percent platelet
      aggregation was 34+/-23, 58+/-15 (P=0.027), 74+/-10 (P=0.002), and 89+/-7
      (P=0.001) in the presence of clopidogrel and 0, 10, 20, and 40 mg of
      atorvastatin, respectively. Erythromycin attenuated platelet aggregation
      inhibition (55+/-12 versus 42+/-12% platelet aggregation; P=0.002), as did
      troleandomycin (78+/-18 versus 45+/-18% platelet aggregation; P<0.0003), whereas
      rifampin enhanced platelet aggregation inhibition (33+/-18 versus 56+/-20%
      platelet aggregation, P=0.001). CONCLUSIONS: CYP3A4 activates clopidogrel.
      Atorvastatin, another CYP3A4 substrate, competitively inhibits this activation.
      Use of a statin not metabolized by CYP3A4 and point-of-care platelet function
      testing may be warranted in patients treated with clopidogrel.

PMID- 12515740
TI  - TAXUS I: six- and twelve-month results from a randomized, double-blind trial on a
      slow-release paclitaxel-eluting stent for de novo coronary lesions.
AB  - BACKGROUND: The TAXUS NIRx stent (Boston Scientific Corp) provides local delivery
      of paclitaxel via a slow-release polymer coating. The TAXUS I trial was the first
      in-human experience evaluating safety and feasibility of the TAXUS NIRx stent
      system compared with bare NIR stents (control) (Boston Scientific Corp) for
      treatment of coronary lesions. METHODS AND RESULTS:  METHODS AND RESULTS: The
      TAXUS I trial was a prospective, double-blind, three-center study randomizing 61
      patients with de novo or restenotic lesions (< or =12 mm) to receive a TAXUS
      (n=31) versus control (n=30) stent (diameter 3.0 or 3.5 mm). Demographics, lesion
      characteristics, clinical outcomes were comparable between the groups. The 30-day
      major adverse cardiac event (MACE) rate was 0% in both groups (P=NS). No stent
      thromboses were reported at 1, 6, 9, or 12 months. At 12 months, the MACE rate
      was 3% (1 event) in the TAXUS group and 10% (4 events in 3 patients) in the
      control group (P=NS). Six-month angiographic restenosis rates were 0% for TAXUS
      versus 10% for control (P=NS) patients. There were significant improvements in
      minimal lumen diameter (2.60+/-0.49 versus 2.19+/-0.65 mm), diameter stenosis
      (13.56+/-11.77 versus 27.23+/-16.69), and late lumen loss (0.36+/-0.48 versus
      0.71+/-0.48 mm) in the TAXUS group (all P<0.01). No evidence of edge restenosis
      was seen in either group. Intravascular ultrasound analysis showed significant
      improvements in normalized neointimal hyperplasia in the TAXUS (14.8 mm3) group
      compared with the control group (21.6 mm3) (P<0.05). CONCLUSIONS: In this
      feasibility trial, the TAXUS slow-release stent was well tolerated and showed
      promise for treatment of coronary lesions, with significant reductions in
      angiographic and intravascular ultrasound measures of restenosis.

PMID- 12515741
TI  - Current use of unopposed estrogen and estrogen plus progestin and the risk of
      acute myocardial infarction among women with diabetes: the Northern California
      Kaiser Permanente Diabetes Registry, 1995-1998.
AB  - BACKGROUND: Little is known about hormone replacement therapy (HRT) and risk for
      myocardial infarction (MI) in diabetic women. We examined associations of current
      HRT, estrogen dosage, and time since HRT initiation with risk of acute MI in
      diabetic women. METHODS AND RESULTS: Cox proportional hazards models, with
      current HRT modeled as a time-dependent covariate, were used to assess the 3-year
      risk of MI. Among 24 420 women without a recent MI (mean age 64.9 years), 1110
      incident MIs were identified. After adjustment for cardiovascular risk factors,
      current HRT was associated with reduced MI risk (relative hazard [RH] 0.84, 95%
      CI 0.72 to 0.98). The RH for MI associated with current estrogen plus progestin
      use was 0.77 (95% CI 0.61 to 0.97), and the RH for MI associated with current
      unopposed estrogen use was 0.88 (95% CI 0.73 to 1.05). Women were at reduced MI
      risk if they were taking a low or medium dose of estrogen (equivalent to <0.625
      or 0.625 mg of conjugated estrogen, respectively) but not a high dose (>0.625 mg
      of conjugated estrogen or its equivalent). Among those whose current use of HRT
      was <1 year, the RH for MI was 1.03 (95% CI 0.74 to 1.44), whereas among users
      for > or =1 year, the RH was 0.81 (95% CI 0.66 to 1.00). Among 580 women with a
      recent MI (mean age 69.2 years), 89 recurrent MIs were identified. An increased
      risk of recurrent MI was observed among current HRT users (RH 1.78, 95% CI 1.06
      to 2.98), which was higher among those with current use for <1 year (RH 3.84, 95%
      CI 1.60 to 9.20). CONCLUSIONS: In women without a recent MI, use of estrogen plus
      progestin was associated with decreased risk of MI. However, HRT was associated
      with increased risk of MI in women with history of a recent MI. Data from
      clinical trials in diabetic women are needed.

PMID- 12515742
TI  - Differential role of K(ATP) channels activated by conjugated estrogens in the
      regulation of myocardial and coronary protective effects.
AB  - BACKGROUND: We have demonstrated that estrogen can reduce myocardial injury in
      ischemia-reperfusion via activation of ATP-sensitive potassium (K(ATP)) channels.
      We sought to determine whether the protective effect of estrogen extends to
      epicardial coronary artery with attenuated vasoconstriction in patients after
      angioplasty by activation of such channels. METHODS AND RESULTS: The study was
      designed to prospectively investigate 41 consecutive patients scheduled for
      elective coronary angioplasty. Pretreatment with estrogen limited myocardial
      ischemia during coronary occlusion and attenuated postangioplasty coronary
      vasoconstriction at the dilated and distal segments. An inhibitor of K(ATP)
      channels, glibenclamide, did not affect coronary vasomotor response, although it
      abolished the beneficial effect of estrogen on myocardial ischemia. Patients to
      whom estrogen was administered after the second balloon deflation experienced a
      similar magnitude of myocardial ischemia as controls but showed significantly
      attenuated vasoconstriction compared with controls (P=0.0001). Endothelin-1
      levels from the great cardiac vein rose significantly from 1.9+/-0.4 to 3.1+/-0.6
      pg/mL (P=0.001) 15 minutes after angioplasty in the control group; this was
      attenuated after estrogen was administered. Significant correlation was found
      between the changes in coronary vasomotion of the dilated segment and endothelin
      1 levels (r=0.65, P<0.0001). CONCLUSIONS: These results demonstrate that estrogen
      is protective against both myocardial ischemia and coronary vasoconstriction
      through different mechanisms. The myocardial effect of estrogen was abolished by
      glibenclamide, which suggests that the cardioprotective effect of estrogen may
      result from activation of K(ATP) channels. In contrast, estrogen-induced
      attenuated vasoconstriction is associated with an attenuated release of
      endothelin-1, independent of K(ATP) activation.

PMID- 12515743
TI  - Modulation of aspirin-insensitive eicosanoid biosynthesis by 6-methylprednisolone
      in unstable angina.
AB  - BACKGROUND: The evidence that inflammation plays a pivotal role in the
      pathophysiology of acute coronary syndromes prompted us to investigate the
      effects of glucocorticoid treatment on leukotriene (LT) C4 and thromboxane (TX)
      A2 biosynthesis in unstable angina. METHODS AND RESULTS: Urinary LTE4 and 11
      dehydro-TXB2 were significantly higher in 12 patients with unstable angina than
      in 12 patients with stable angina and 12 patients with nonischemic chest pain.
      Furthermore, we randomized the unstable angina patients to receive intravenous 6
      methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and
      collected 12 consecutive 6-hour urine samples before and during the infusions.
      LTE4 excretion showed a time-dependent decrease in the 6-MP group but did not
      decrease during placebo. Furthermore, during myocardial ischemia, LTE4 was
      significantly higher before 6-MP infusion than during steroid therapy. In
      contrast, 11-dehydro-TXB2 did not differ significantly during 6-MP versus
      placebo. Myocardial ischemia elicited by stress test in the stable angina
      patients was not accompanied by any change in LTE4 and 11-dehydro-TXB2, thus
      ruling out a role of ischemia per se in the induction of increased eicosanoid
      production. CONCLUSIONS: Increased production of vasoactive LT and TX may occur
      in unstable angina despite conventional antithrombotic and antianginal treatment.
      Glucocorticoids can suppress LTC4 biosynthesis in the short term and may provide
      an interesting tool to explore the pathophysiological significance of
      inflammatory cell activation in this setting.

PMID- 12515744
TI  - Intravascular ultrasound guidance improves angiographic and clinical outcome of
      stent implantation for long coronary artery stenoses: final results of a
      randomized comparison with angiographic guidance (TULIP Study).
AB  - BACKGROUND: Long coronary lesions treated with stents have a poor outcome. This
      study compared the 6-month outcome of stent implantation for long lesions in
      patients randomized to intravascular ultrasound (IVUS; n=73) or angiographic
      guidance (n=71). METHODS AND RESULTS: Stenoses >20 mm in length and a reference
      diameter that permitted a stent diameter > or =3 mm were eligible. Primary end
      points were 6-month minimal lumen diameter (MLD) and the combined end point of
      death, myocardial infarction, and target-lesion revascularization (TLR). Baseline
      clinical and angiographic data were comparable in both groups. At 6 months, MLD
      in the IVUS group (1.82+/-0.53 mm) was larger than in the angiography group
      (1.51+/-0.71 mm; P=0.042). TLR and combined end-point rates at 6 months were 4%
      (n=3) and 6% (n=4) in the IVUS group and 14% (n=10) and 20% (n=14) in the
      angiography group, respectively (P=0.037 for TLR and P=0.01 for combined events).
      Restenosis (>50% diameter stenosis) was found in 23% of the IVUS group and 45% of
      the angiography group (P=0.008). At 12 months, TLR and the combined end point
      occurred in 10% (n=7) and 12% (n=9) of the IVUS group and 23% (n=17) and 27%
      (n=19) of the angiography group (P=0.018 and P=0.026), respectively. CONCLUSIONS:
      Angiographic and clinical outcome up to 12 months after long stent placement
      guided by IVUS is superior to guidance by angiography.

PMID- 12515745
TI  - Effect of nasal continuous positive airway pressure treatment on blood pressure
      in patients with obstructive sleep apnea.
AB  - BACKGROUND: There is increasing evidence that obstructive sleep apnea (OSA) is an
      independent risk factor for arterial hypertension. Because there are no
      controlled studies showing a substantial effect of nasal continuous positive
      airway pressure (nCPAP) therapy on hypertension in OSA, the impact of treatment
      on cardiovascular sequelae has been questioned altogether. Therefore, we studied
      the effect of nCPAP on arterial hypertension in patients with OSA. METHODS AND
      RESULTS: Sixty consecutive patients with moderate to severe OSA were randomly
      assigned to either effective or subtherapeutic nCPAP for 9 weeks on average.
      Nocturnal polysomnography and continuous noninvasive blood pressure recording for
      19 hours was performed before and with treatment. Thirty two patients, 16 in each
      group, completed the study. Apneas and hypopneas were reduced by approximately
      95% and 50% in the therapeutic and subtherapeutic groups, respectively. Mean
      arterial blood pressure decreased by 9.9+/-11.4 mm Hg with effective nCPAP
      treatment, whereas no relevant change occurred with subtherapeutic nCPAP
      (P=0.01). Mean, diastolic, and systolic blood pressures all decreased
      significantly by approximately 10 mm Hg, both at night and during the day.
      CONCLUSIONS: Effective nCPAP treatment in patients with moderate to severe OSA
      leads to a substantial reduction in both day and night arterial blood pressure.
      The fact that a 50% reduction in the apnea-hypopnea index did not result in a
      decrease in blood pressure emphasizes the importance of highly effective
      treatment. The drop in mean blood pressure by 10 mm Hg would be predicted to
      reduce coronary heart disease event risk by 37% and stroke risk by 56%.

PMID- 12515746
TI  - Incremental value of ultrasonic tissue characterization (backscatter) in the
      evaluation of left ventricular myocardial structure and mechanics in essential
      arterial hypertension.
AB  - BACKGROUND: Ultrasonic backscatter parameters were analyzed in hypertensive
      patients and divided into groups according to both severity of left ventricular
      hypertrophy (LVH) (group A: no LVH [n=52]; B: mild to moderate LVH [n=55]; and C:
      severe LVH [n=10]) and left ventricular geometry (normal geometry [n=44];
      concentric remodeling [n=8]; concentric hypertrophy [n=25]; and eccentric
      hypertrophy [n=40]). METHODS AND RESULTS: We studied 117 male, essential
      hypertensive patients and 19 normotensive, age-matched (40+/-5 years), healthy
      subjects who served as controls. Ambulatory and office blood pressure
      measurements were taken and 2-dimensional Doppler echocardiography and ultrasonic
      myocardial integrated backscatter (IBS) were performed. A group from the
      hypertensive study population (n=16) was observed after a period of
      pharmacological antihypertensive treatment to determine the behavior of
      backscatter parameters in relation to eventual regression of left ventricular
      mass (LVM). The cyclic variation index (CVIs) of the backscatter signal at the
      septum level was grouped according to each LVM level and was 29.4+/-9.3
      (controls), 15+/-11 (group A), 9.5+/-10 (group B), and -1.5+/-8.6 (group C)
      (P<0.001). CVI septum values grouped according to left ventricular geometry were
      15+/-11 (normal geometry), 12+/-7 (concentric remodeling), 7+/-11 (concentric
      hypertrophy), and 7.8+/-11 (eccentric hypertrophy) (P<0.01). Follow-up data
      demonstrate a significant reduction of LVM after therapy, as well as a
      significant increase in CVIs toward normal values. CONCLUSIONS: Hypertensive
      patients with higher LVM had the worst prognosis; in fact, those patients had the
      most significant CVI alterations. Regression of LVM subsequent to chronic
      pharmacological therapy induces a normalization of ultrasonic backscatter
      parameters. Ultrasonic tissue characterization (backscatter) analysis could allow
      early identification of patients at risk of developing complications of
      hypertensive cardiopathy.

PMID- 12515747
TI  - Sustained hemodynamic effects of intravenous levosimendan.
AB  - BACKGROUND: The short-term infusion of levosimendan (Levo) improves hemodynamic
      function in patients with decompensated heart failure. The metabolites of Levo
      have a prolonged half-life, and one is hemodynamically active. The goal of this
      study was to determine whether the hemodynamic effects of Levo are sustained
      during a long-term infusion and beyond the discontinuation of drug infusion.
      METHODS AND RESULTS: Patients with decompensated heart failure received
      escalating infusion rates of intravenous Levo (n=98) or placebo (n=48) for 6
      hours. At the end of 6 hours, 85 of the Levo-treated patients were continued on
      open-label drug for a total of 24 hours, at which time they were randomized 1:1
      to an additional 24 hours of Levo (n=43) or placebo (n=42). The hemodynamic
      effects observed at 24 hours were maintained at 48 hours in both the continuation
      and withdrawal groups and did not differ between groups. Although the plasma
      concentration of Levo decreased rapidly in the withdrawal group, concentrations
      of the active metabolite OR-1896 were similar in the continuation and withdrawal
      groups at 24 hours and increased further (3.5-fold to 4-fold) and to a similar
      extent in both groups at 48 hours. CONCLUSIONS: The hemodynamic effects of Levo
      were maintained during a 48-hour continuous infusion and for at least 24 hours
      after discontinuation of a 24-hour infusion. The active metabolite OR-1896
      increased for at least 24 hours after cessation of drug infusion and may account
      for the prolonged hemodynamic effects of Levo.

PMID- 12515748
TI  - Elevations of inflammatory and procoagulant biomarkers in elderly persons with
      renal insufficiency.
AB  - BACKGROUND: Renal insufficiency has been associated with cardiovascular disease
      events and mortality in several prospective studies, but the mechanisms for the
      elevated risk are not clear. Little is known about the association of renal
      insufficiency with inflammatory and procoagulant markers, which are potential
      mediators for the cardiovascular risk of kidney disease. METHODS AND RESULTS: The
      cross-sectional association of renal insufficiency with 8 inflammatory and
      procoagulant factors was evaluated using baseline data from the Cardiovascular
      Health Study, a population-based cohort study of 5888 subjects aged > or =65
      years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were
      measured in nearly all participants; interleukin-6, intercellular adhesion
      molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in
      nearly half of participants. Renal insufficiency was defined as a serum
      creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men.
      Multivariate linear regression was used to compare adjusted mean levels of each
      biomarker in persons with and without renal insufficiency after adjustment for
      other baseline characteristics. Renal insufficiency was present in 647 (11%) of
      Cardiovascular Health Study participants. After adjustment for baseline
      differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor
      VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly
      greater among persons with renal insufficiency (P<0.001). In participants with
      clinical, subclinical, and no cardiovascular disease at baseline, the positive
      associations of renal insufficiency with these inflammatory and procoagulant
      markers were similar. CONCLUSION: Renal insufficiency was independently
      associated with elevations in inflammatory and procoagulant biomarkers. These
      pathways may be important mediators leading to the increased cardiovascular risk
      of persons with kidney disease.

PMID- 12515749
TI  - Simvastatin initiated early after heart transplantation: 8-year prospective
      experience.
AB  - BACKGROUND: Randomized clinical trials have demonstrated that the use of statins
      in heart transplant patients lowers cholesterol levels and significantly reduces
      mortality and the development of transplant vasculopathy. The aim of the present
      study was to test these effects and the safety of statin therapy over an 8-year
      period. METHODS AND RESULTS: In 1991, a prospective, randomized, unmasked study
      was initiated to compare the efficacy of simvastatin, started on the fourth
      postoperative day (n=35), with that of dietary therapy alone (n=37). Because of
      significantly improved survival and a lower incidence of transplant vasculopathy,
      most patients in both groups received statins as open-label prescriptions after 4
      years. After 8 years, the Kaplan-Meier survival rate was 88.6% in the simvastatin
      group versus 59.5% in the control group (P<0.006 by log rank; hazard ratio, 0.24;
      95% CI, 0.08 to 0.71). Deaths in the simvastatin and control groups were due to
      transplant vasculopathy (1 versus 4; P<0.2), severe transplant rejection (1
      versus 5; P<0.1), malignancies (0 versus 3; P<0.1), and other causes (2 versus 3;
      P<0.7). The incidence of transplant vasculopathy confirmed by angiography was
      24.4% in the simvastatin group versus 54.7% in the control group (P<0.02 by log
      rank). There was no difference in organ function between the 2 groups. No severe
      adverse effects of the therapy were observed up to the end of the 8-year
      observation period. CONCLUSIONS: Simvastatin therapy initiated early after heart
      transplantation leads to significantly better 8-year survival rates and a
      significantly lower incidence of transplant vasculopathy without impairment of
      organ function or severe adverse effects.

PMID- 12515750
TI  - Adenoviral gene transfer of fortilin attenuates neointima formation through
      suppression of vascular smooth muscle cell proliferation and migration.
AB  - BACKGROUND: Fortilin, a recently characterized nuclear antiapoptotic factor
      structurally distinct from inhibitor of apoptosis proteins (IAPs) and Bcl-2
      family member proteins, has been suggested to be involved in cell survival and
      regulation of apoptosis within the cardiovascular system. In this continued
      investigation, we characterized the influence of adenovirus-mediated fortilin (Ad
      fortilin) gene delivery on vascular remodeling after experimental angioplasty.
      METHODS AND RESULTS: Vessel wall expression of Ad-fortilin or adenoviral
      luciferase (Ad-luc) was demonstrated 72 hours and 14 days after rat carotid
      artery (CA) balloon angioplasty. Morphometric analyses 14 days after injury
      revealed significantly diminished neointima development in the Ad-fortilin
      treated CAs compared with Ad-luc or PBS controls, with no changes in medial wall
      morphometry observed between the 3 groups. The Ad-fortilin-treated CAs
      demonstrated a 50% reduction in medial wall proliferating cell nuclear antigen
      (PCNA) labeling after 72 hours, with significantly reduced neointimal and medial
      wall PCNA labeling and cell counts after 14 days. Terminal dUTP nick-end labeling
      results and morphological changes characteristic of programmed cell death suggest
      a trend toward reduced apoptosis in the fortilin-transfected balloon-injured
      vessels compared with Ad-luc injured controls. Temporal analysis of human aorta
      smooth muscle cell (SMC) proliferation demonstrated a marked time-dependent
      inhibition in Ad-fortilin treated SMCs without the influence of elevated
      apoptosis. Thymidine incorporation was significantly inhibited in the Ad-fortilin
      treated cells compared with Ad-luc controls. Ad-fortilin transfected SMCs also
      demonstrated significantly decreased migration compared with Ad-luc controls.
      CONCLUSIONS: These cumulative results suggest that the novel antiapoptotic
      protein fortilin may play important redundant pathophysiological roles in
      modulating the vascular response to experimental angioplasty through suppression
      of SMC proliferation and migration concomitant with reduction of vessel wall
      apoptosis.

PMID- 12515751
TI  - Fluvastatin enhances the inhibitory effects of a selective angiotensin II type 1
      receptor blocker, valsartan, on vascular neointimal formation.
AB  - BACKGROUND: The present studies were undertaken to investigate the potential
      effect of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) to
      enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT1) receptor
      blocker (ARB) on vascular neointimal formation and to explore the cellular
      mechanism of cross-talk of the AT1 receptor and statin in vascular smooth muscle
      cells (VSMCs). METHODS AND RESULTS: Neointimal formation and the proliferation of
      VSMCs induced by cuff placement around the femoral artery were significantly
      inhibited by treatment with an ARB, valsartan, at a dose of 0.1 mg x kg(-1) x d(
      1) and with fluvastatin at a dose of 1 mg x kg(-1) x d(-1), which did not
      influence mean arterial blood pressure or plasma cholesterol level, whereas
      valsartan or fluvastatin alone at these doses did not affect neointimal formation
      or the proliferation of VSMCs. Pretreatment with fluvastatin (approximately 5
      micromol/L) for 24 hours significantly inhibited Ang II (1 micromol/L)-mediated
      DNA synthesis and c-fos promoter activity in cultured VSMCs. Moreover,
      pretreatment of VSMCs with fluvastatin significantly inhibited Ang II-mediated
      extracellular signal-regulated kinase (ERK) activation and tyrosine- and serine
      phosphorylation of signal transducer and activator of transcription (STAT)1 and
      STAT3. AT1 receptor-mediated recruitment of Rac-1 to Janus kinase (Jak)
      family/STATs was also inhibited by fluvastatin. Consistent with these in vitro
      results, phosphorylation of ERK, STAT1, and STAT3 was attenuated by the
      coadministration of valsartan and fluvastatin even at low doses in vivo.
      CONCLUSION: These results suggest that the cholesterol-independent inhibition of
      AT1 receptor-mediated VSMC proliferation by statins may contribute to the
      beneficial effects of statins combined with an ARB on vascular diseases.

PMID- 12515752
TI  - Quantification of macrophage content in atherosclerotic plaques by optical
      coherence tomography.
AB  - BACKGROUND: Macrophage degradation of fibrous cap matrix is an important
      contributor to atherosclerotic plaque instability. An imaging technology capable
      of identifying macrophages in patients could provide valuable information for
      assessing plaque vulnerability. Optical coherence tomography (OCT) is a new
      intravascular imaging modality that allows cross-sectional imaging of tissue with
      a resolution of approximately 10 micro m. The aim of this study was to
      investigate the use of OCT for identifying macrophages in fibrous caps. METHODS
      AND RESULTS: OCT images of 26 lipid-rich atherosclerotic arterial segments
      obtained at autopsy were correlated with histology. Cap macrophage density was
      quantified morphometrically by immunoperoxidase staining with CD68 and smooth
      muscle actin and compared with the standard deviation of the OCT signal intensity
      at corresponding locations. There was a high degree of positive correlation
      between OCT and histological measurements of fibrous cap macrophage density
      (r=0.84, P<0.0001) and a negative correlation between OCT and histological
      measurements of smooth muscle actin density (r=-0.56, P<0.005). A range of OCT
      signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity
      and specificity for identifying caps containing >10% CD68 staining. CONCLUSIONS:
      The high contrast and resolution of OCT enables the quantification of macrophages
      within fibrous caps. The unique capabilities of OCT for fibrous cap
      characterization suggest that this technology may be well suited for identifying
      vulnerable plaques in patients.

PMID- 12515753
TI  - Truncated estrogen receptor alpha 46-kDa isoform in human endothelial cells:
      relationship to acute activation of nitric oxide synthase.
AB  - BACKGROUND: Estrogen acutely activates endothelial nitric oxide synthase (eNOS).
      However, the identity of the receptors involved in this rapid response remains
      unclear. METHODS AND RESULTS: We detected an estrogen receptor alpha (ERalpha)
      transcript in human endothelial cells that encodes a truncated 46-kDa ERalpha
      (Delta1a-hERalpha-46). A corresponding 46-kDa ERalpha protein was identified in
      endothelial cell lysates. Transfection of cDNAs encoding the full-length ERalpha
      (ERalpha-66) and Delta1a-hERalpha-46 resulted in appropriately sized recombinant
      proteins identified by anti-ERalpha antibodies. Confocal microscopy revealed that
      a proportion of both ERalpha-66 and hERalpha-46 was localized outside the nucleus
      and mediated specific cell-surface binding of estrogen as assessed by FITC
      conjugated, BSA-estrogen binding studies. Both ERalpha isoforms colocalized with
      eNOS and mediated acute activation of eNOS in response to estrogen stimulation.
      However, estrogen-stimulated transcriptional activation mediated by Delta1a
      hERalpha-46 was much less than with ERalpha-66. Furthermore, Delta1a-hERalpha-46
      inhibited classical hERalpha-66-mediated transcriptional activation in a dominant
      negative fashion. CONCLUSIONS: These findings suggest that expression of an
      alternatively spliced, truncated ERalpha isoform in human endothelial cells
      confers a unique ability to mediate acute but not transcriptional responses to
      estrogen.

PMID- 12515754
TI  - Doxazosin induces apoptosis in cardiomyocytes cultured in vitro by a mechanism
      that is independent of alpha1-adrenergic blockade.
AB  - BACKGROUND: The alpha1-adrenoceptor-blocking antihypertensive doxazosin has been
      associated with increased risk of heart failure and is known to induce prostate
      cell apoptosis. We hypothesized that it might also induce apoptosis in
      cardiomyocytes. METHODS AND RESULTS: Hoechst dye vital staining and flow
      cytometry provided evidence that doxazosin induced apoptosis time- and dose
      dependently in cardiomyocytes of the HL-1 cell line. TUNEL assays and 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) viability test
      confirmed that doxazosin induced DNA damage and cell death in these cells. MTT
      tests showed that doxazosin treatment decreased cell viability in primary
      cultures of neonatal rat cardiomyocytes, and Hoechst dye vital staining
      demonstrated doxazosin-induced apoptosis in primary cultures of human adult
      cardiomyocytes. The proapoptotic effect of doxazosin on cardiomyocytes seems not
      to depend on alpha1 blockade, because it was not modified by cotreatment with
      alpha- or beta-adrenergic agonists or with the irreversible alpha1-blocker
      phenoxybenzamine and because doxazosin also decreased the viability of NIH 3T3
      cells, which lack alpha1-adrenoceptors. It also does not involve calcineurin,
      being unaffected by the presence of the calcineurin inhibitors cyclosporin A and
      FK506. Three other alpha1-blockers were also investigated; prazosin was
      proapoptotic, like doxazosin, but 5-methylurapidil and terazosin were not.
      CONCLUSIONS: The alpha1-blockers doxazosin and prazosin induce the apoptosis of
      cardiomyocytes cultured in vitro by a mechanism that is independent of alpha1
      blockade and calcineurin.

PMID- 12515755
TI  - Magnetic resonance image-guided transcatheter closure of atrial septal defects.
AB  - BACKGROUND: Recent developments in cardiac MRI have extended the potential
      spectrum of diagnostic and interventional applications. The purpose of this study
      was to test the ability of MRI to perform transcatheter closures of secundum type
      atrial septal defects (ASD) and to assess ASD size and changes in right cardiac
      chamber volumes in the same investigation. METHODS AND RESULTS: In 7 domestic
      swine (body weight, 38+/-13 kg), an ASD (Q(p):Q(s)=1.7+/-0.2) was created
      percutaneously by balloon dilation of the fossa ovalis. The ASD was imaged and
      sized by both conventional radiography and MRI. High-resolution MRI of the ASD
      diameters correlated well with postmortem examination (r=0.97). Under real-time
      MR fluoroscopy, the introducer sheath was tracked toward the left atrium with the
      use of novel miniature MR guide wires. The defect was then closed with an
      Amplatzer Septal Occluder. In all animals, it was possible to track and
      interactively control the position of the guide wire within the vessels and the
      heart, including the successful deployment of the Amplatzer Septal Occluder.
      Right atrial and ventricular volumes were calculated before and after the
      intervention by using cine-MRI. Both volumes were found to be significantly
      reduced after ASD closure (P<0.005). CONCLUSIONS: These in vivo studies
      demonstrate that catheter tracking and ASD device closure can be performed under
      real-time MRI guidance with the use of intravascular antenna guide wires. High
      resolution imaging allows accurate determination of ASD size before the
      intervention, and immediate treatment effects such as changes in right cardiac
      volumes can also be measured.

PMID- 12515756
TI  - Arterial and cardiac aging: major shareholders in cardiovascular disease
      enterprises: Part I: aging arteries: a "set up" for vascular disease.

PMID- 12515757
TI  - Images in cardiovascular medicine. Coronary artery patency after metallic stent
      implantation evaluated by multislice computed tomography.

PMID- 12515758
TI  - ACC/AHA 2002 guideline update for the management of patients with chronic stable
      angina--summary article: a report of the American College of Cardiology/American
      Heart Association Task Force on Practice Guidelines (Committee on the Management
      of Patients With Chronic Stable Angina).

PMID- 12515759
TI  - Images in cardiovascular medicine. Thromboembolism in real-time two-dimensional
      echocardiography.

PMID- 12515760
TI  - Cardiology patient pages. Exercise and cardiovascular health.

PMID- 12515761
TI  - Reduction of total homocysteine levels by oral folic acid fails to improve
      endothelial function in children with chronic renal failure.

PMID- 12515762
TI  - NADPH-oxidase might also act as an antithrombotic.

PMID- 12515763
TI  - Could elevated C-reactive protein in patients with obstructive sleep apnea be due
      to obesity per se?

PMID- 12515764
TI  - "Hibernating" myocardium: not only a matter of semantics.

PMID- 12515765
TI  - Is percutaneous left atrial appendage transcatheter occlusion an alternative to
      oral anticoagulation in patients with atrial fibrillation?

PMID- 12515766
TI  - B-type natriuretic peptide predicts sudden death in patients with chronic heart
      failure.

PMID- 12515767
TI  - Perchance to dream: Mr. Romanow's final report.

PMID- 12515770
TI  - Whither preventive medicine?

PMID- 12515771
TI  - Whither preventive medicine?

PMID- 12515772
TI  - Whither preventive medicine?

PMID- 12515773
TI  - Whither preventive medicine?

PMID- 12515774
TI  - Weighing the risks and benefits of tamoxifen.

PMID- 12515776
TI  - Getting the word out.

PMID- 12515778
TI  - Hiphuggers' tingly thighs.

PMID- 12515779
TI  - A pain in the back.

PMID- 12515780
TI  - Risk factors for elevated HIV incidence among Aboriginal injection drug users in
      Vancouver.
AB  - BACKGROUND: Because of established links between entrenched poverty and risk of
      HIV infection, there have long been warnings that HIV/AIDS will
      disproportionately affect Aboriginal people in Canada. We compared HIV incidence
      rates among Aboriginal and non-Aboriginal injection drug users (IDUs) in
      Vancouver and studied factors associated with HIV seroconversion among Aboriginal
      participants. METHODS: This analysis was based on 941 participants (230
      Aboriginal people) recruited between May 1996 and December 2000 who were
      seronegative at enrollment and had completed at least one follow-up visit.
      Incidence rates were calculated using the Kaplan-Meier method. The Cox
      proportional hazards regression model was used to identify independent predictors
      of time to HIV seroconversion among female and male Aboriginal IDUs. RESULTS: As
      of May 31, 2001, seroconversion had occurred in 112 (11.9%) of the participants,
      yielding a cumulative incidence of HIV infection at 42 months of 12.7% (95%
      confidence interval [CI] 10.3%-15.1%). The cumulative incidence at 42 months was
      significantly higher among the Aboriginal participants than among the non
      Aboriginal participants (21.1% v. 10.7%, p < 0.001). This elevation in risk was
      present in both female and male Aboriginal IDUs. Among the female Aboriginal
      IDUs, frequent speedball (combined cocaine and heroin) injection (adjusted
      relative risk [RR] 3.1; 95% CI 1.4-7.1) and going on binges of injection drug use
      (adjusted RR 2.3; 95% CI 1.0-5.2) were found to be independent predictors of HIV
      seroconversion. Among the male Aboriginal IDUs, the independent predictors of
      seroconversion were frequent speedball injection (adjusted RR 2.9; 95% CI 1.0
      8.5) and frequent cocaine injection (adjusted RR 2.5; 95% CI 1.0-6.5).
      INTERPRETATION: In Vancouver, Aboriginal IDUs are becoming HIV positive at twice
      the rate of non-Aboriginal IDUs. Our findings emphasize the urgent need for an
      appropriate and effective public health strategy--planned and implemented in
      partnership with Aboriginal AIDS service organizations and the Aboriginal
      community--to reduce the harms of injection drug use in this population.

PMID- 12515781
TI  - Parents' responses to symptoms of respiratory tract infection in their children.
AB  - BACKGROUND: Little is known about the determinants of parental response when
      children appear to have a respiratory tract infection (RTI). Our objective was to
      identify what factors predict that parents will seek medical consultation.
      METHODS: In a prospective cohort study we consecutively recruited 400 children
      aged 2 months to 12 years from the urban, largely middle-class, primary-care
      practices of 7 pediatricians in Toronto. Baseline demographic data were collected
      and the children followed by telephone inquiry until an RTI developed or 6 months
      elapsed. Data about any medical consultation for the RTI were collected. The
      parents completed a questionnaire on clinical features and parental
      interpretations and concerns. Potential predictors of consultation were organized
      into 4 domains: family factors, principal complaints, functional burden of
      illness (determined with a validated measure, the Canadian Acute Respiratory
      Illness and Flu Scale [CARIFS]) and parental interpretation of the illness. Key
      variables for each domain were derived by endorsement, correlation and
      combination, and univariate association with the outcome (medical consultation).
      A model was created to identify independent predictors of consultation. RESULTS:
      Of the 383 children (96%) for whom the study was completed, 275 (72%) had
      symptoms of an RTI within 6 months after recruitment. Medical consultation was
      sought for 140 (56%) of the 251 for whom further data were available. The
      questionnaire data and follow up were complete for 197 (78%) of the 251. Children
      with earaches compared to children without were more likely to be taken to a
      physician (odds ratio [OR] 10.2; 95% confidence interval [CI] 2.8-37.4), as were
      children with high fever (temperature > 40 degrees C) compared to children with
      no fever or fever < or = 40 degrees C (OR 3.2; 95% CI 1.2-8.6). Parents who rated
      their children as having a complaint that was severe or persisting for more than
      24 hours were more likely to see a physician than parents who rated their
      children as having no complaints (OR 8.5; 95% CI 2.3-32.0). Parental concern that
      the illness had an unusual course, with prolonged duration or deterioration (OR
      5.7; 95% CI 1.3-24.8), that the child had a specific illness (OR 2.9; 95% CI 1.1
      7.7) or that specific treatment was needed (OR 5.0; 95% CI 1.1-23.1), compared to
      children with no illnesses or need for treatment, also predicted consultation
      with a physician. Parents' postsecondary education (OR 4.0; 95% CI 1.1-14.6),
      compared to parents with less than postsecondary education, was the only parental
      factor that independently predicted taking a child to see a physician. Child's
      age 48 months or less was the only child factor that independently predicted
      physician consultation (0-6 months, OR 9.2, 95% CI 1.4-58.1; 7-12 months, OR
      17.3, 95% CI 2.0-147.2; 13-24 months, OR 9.2, 95% CI 1.3-63.6; 25-48 months, OR
      5.2, 95% CI 0.8-34.4). Neither family demographics nor functional burden of
      illness predicted consultation. INTERPRETATION: Generally, parents choose
      reasonable criteria for seeking physician advice. However, their perceptions and
      interpretations may be based in part on limited understanding of some factors.
      Further research is necessary to determine how these findings can be used to
      improve anticipatory guidance to parents and better address parental concerns.

PMID- 12515782
TI  - Trends in prostate cancer incidence and mortality: an analysis of mortality
      change by screening intensity.
AB  - BACKGROUND: The rate of death from prostate cancer has recently declined in many
      areas of the world. Over the past 15 years prostate-specific antigen (PSA)
      screening has increased in popularity, which has resulted in increases in the
      incidence of prostate cancer. Over the same period there have been changes in the
      management of the disease and, in particular, the use of androgen ablation. We
      set out to examine the relation between changes in prostate cancer incidence (a
      surrogate for PSA screening) and subsequent changes in mortality in regions using
      common treatment recommendations. METHODS: We used data from prostate cancer
      cases and deaths reported to the British Columbia Cancer Registry during 1985
      1999 to examine trends in incidence and mortality in 88 small health areas (SHAs)
      among men aged 50-74 years. We conducted 2 analyses. In the first we classified
      the SHAs by intensity of PSA screening (low, medium or high) according to their
      ranked age-standardized incidence rate of prostate cancer in 1990-1994 and
      examined subsequent trends in prostate cancer mortality. In the second analysis
      we examined the SHA-specific relative change in prostate cancer incidence between
      1985-1989 and 1990-1994 and correlated it with the relative change in mortality
      for cases diagnosed after 1990. RESULTS: Between 1985-1989 and 1990-1994 the
      incidence of prostate cancer increased by 53.2% and 14.6% among men aged 50-74
      and those 75 and over respectively. Between 1985-1989 and 1995-1999 prostate
      cancer mortality declined by 17.6% and 7.9% in the 2 age groups respectively.
      Among men aged 50-74 years SHAs with low, middle and high levels of screening had
      respective increases in prostate cancer incidence of 5.4%, 53.6% and 70.5%
      between 1985-1989 and 1990-1994. Corresponding decreases in mortality between
      1985-1989 and 1995-1999 were 28.9%, 18.0% and 13.5%. Mortality declines were
      greatest in SHAs with low screening levels (p = 0.032). Before 1990 prostate
      cancer mortality was similar in the 3 screening groups (p = 0.72). Regions with
      the smallest increases in incidence had the largest declines in mortality.
      INTERPRETATION: We found no association between the intensity of PSA screening
      and subsequent decreases in prostate cancer mortality.

PMID- 12515783
TI  - Factors influencing childhood influenza immunization.
AB  - Following the launch of a publicly funded influenza immunization program for all
      residents of Ontario over the age of 6 months, we evaluated 203 parents of
      children who presented to our emergency department between January and March of
      the following year (2001). Overall, 54 (27%) of the children had been vaccinated.
      Parents of non-immunized children were more likely to believe that immunization
      resulted in a flu-like illness (42% v. 17%; p = 0.001), caused side effects that
      were more severe than having influenza (36% v. 17%; p = 0.010) and weakened the
      immune system (52% v. 24%; p < 0.001). Parents of both immunized and non
      immunized children incorrectly identified gastrointestinal symptoms as symptoms
      of influenza. The primary reason for deciding against immunization was the belief
      that their child was not at risk. After adjustment, children with a chronic
      disease were more likely than those without a chronic disease to be immunized
      (adjusted odds ratio [OR] 4.7, 95% confidence interval [CI] 1.8-12.6). Children
      of parents who discussed immunization with a physician were more likely to be
      immunized than those who had not discussed immunization with a physician (OR 6.8,
      95% CI 2.4-19.2).

PMID- 12515784
TI  - Upper respiratory tract infections in children--why do parents seek medical
      consultation?

PMID- 12515785
TI  - Radical prostatectomy as treatment for prostate cancer.

PMID- 12515786
TI  - The treatment of influenza with antiviral drugs.
AB  - Influenza vaccination with current inactivated vaccines homologous to the
      prevalent wild-type virus can reduce influenza illness in 75%-80% of healthy
      adults. Vaccine is recommended for all individuals with chronic underlying
      diseases and for those aged 65 years or older. Although influenza vaccination is
      still advocated for patients with blunted immunity, protection rates are not as
      high, running at 40% for frail institutionalized elderly people. The influenza
      antiviral agents amantadine or rimantadine, zanamivir and oseltamivir can modify
      the severity of illness and reduce the duration of illness by about 1.5-2.5 days.
      Amantadine inhibits only influenza A. Resistant virus may emerge in up to 33% of
      amantadine-treated patients in the first 5 days of treatment and be transmitted
      to susceptible close contacts. Side effects are usually mild in short courses of
      treatment. The neuraminidase inhibitor drugs zanamivir and oseltamivir act on
      both influenza A and B. Treatment is most effective when given within 30-36 hours
      after the onset of illness, and the earlier the better. Influenza should be
      treated with antiviral drugs in unvaccinated and vaccinated high-risk patients,
      as well as immunosuppressed patients with influenza-like illness, in periods of
      confirmed influenza prevalence. These drugs may be of great value in the event of
      a major viral antigenic shift that causes pandemic influenza, if an adequate
      supply can be sustained.

PMID- 12515787
TI  - Clinical nutrition: 8. The role of nutrition in the prevention of iron deficiency
      anemia in infants, children and adolescents.

PMID- 12515788
TI  - Norwalk-like viruses: when the runs can slow you down.

PMID- 12515789
TI  - Accutane (isotretinoin) and psychiatric adverse effects.

PMID- 12515790
TI  - Radical prostatectomy or watchful waiting in early prostate cancer?

PMID- 12515791
TI  - A man with painless scrotal swelling and peripheral edema.

PMID- 12515796
TI  - CMA frowns on prescribing rights for pharmacists.

PMID- 12515798
TI  - Sign in office ends clash between MD's beliefs, patients' requests.

PMID- 12515799
TI  - City bans medical devices that contain mercury.

PMID- 12515803
TI  - On-call duties total over 7.5 days a month for 25% of surgeons.

PMID- 12515806
TI  - Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule
      nectin at neuroepithelial cells of developing mouse.
AB  - PAR-3 is a cell polarity protein that localizes at tight junctions (TJs) by
      direct binding to an immunoglobulin (Ig)-like cell-cell adhesion molecule JAM-1
      in mammalian epithelial cells. Another Ig-like cell-cell adhesion molecule nectin
      plays a role in the localization of JAM-1 at TJs in epithelial cells. Nectin
      furthermore plays a role in the organization of adherens junctions (AJs) and TJs.
      Nectin comprises a family of four members, nectin-1, -2, -3, and -4. Nectins are
      associated with the actin cytoskeleton through afadin, of which the PDZ domain
      binds to nectins through their C-terminal four amino acids. We show here that PAR
      3 binds to nectin-1 and -3 in neuroepithelial cells of the embryonic
      telencephalon, which are equipped with AJs, but not with typical TJs. Nectin-1, 
      2, -3, and afadin, but not JAM-1, were concentrated at AJs in neuroepithelial
      cells of the embryonic telencephalon at E13.5 and PAR-3 co-localized with
      nectins. PAR-3 was co-immunoprecipitated with nectin-1 and -3, but not with
      nectin-2 or JAM-1, from the mouse whole brain at E13.5. Recombinant PAR-3
      stoichiometrically bound to recombinant nectin-1 and -3. The first one of the
      three PDZ domains of PAR-3 bound to the C-terminal four amino acids of nectin-1
      and -3. The affinities of PAR-3 and afadin for nectin-1 and -3 were similar.
      Cadherin-deficient L cells expressing nectin-1 and -3 formed nectin-1- and -3
      based cell-cell junctions, respectively, where PAR-3 as well as afadin was
      recruited. These results indicate that nectin-1 and -3 are involved in the
      localization of PAR-3 at AJs in the neuroepithelial cells of the embryonic
      telencephalon.

PMID- 12515807
TI  - Approaches to define antigen receptor-induced serine kinase signal transduction
      pathways.
AB  - In the present report we describe the properties of a novel phospho-specific
      antiserum that has opened a route to the characterization of antigen receptor
      activated serine kinase pathways in lymphocytes. The basis for the present work
      was that Ser-21 in glycogen synthase kinase 3alpha is robustly phosphorylated
      following antigen receptor triggering. We predicted accordingly that antigen
      receptors would also stimulate phosphorylation of other proteins with a similar
      sequence. To test this idea we raised an antibody against the phospho-peptide
      RARTSpSFAEP, where pS is a phospho-serine corresponding to the glycogen synthase
      kinase 3alpha Ser-21 sequence. The resulting antiserum was called phospho
      antibody for proteomics-1 (PAP-1). The present study describes the properties of
      PAP-1 and shows that it can reveal quite striking differences in the phospho
      proteome of different cell types and is able to pinpoint new targets in important
      signal transduction pathways. PAP-1 was used to map protein phosphorylations
      regulated by the antigen receptor in T cells. One of these PAP-1-reactive
      proteins was purified and revealed to be a previously unrecognized target for
      antigen receptor signal transduction, namely an "orphan" adapter SLY (Src
      homology 3 (SH3) domain-containing protein expressed in lymphocytes). The use of
      sera detecting specific phosphorylation sites is thus proved as a powerful method
      for the discovery of novel downstream components of antigen receptor signals in T
      cells.

PMID- 12515808
TI  - A dangerous liaison between two major killers: Mycobacterium tuberculosis and HIV
      target dendritic cells through DC-SIGN.

PMID- 12515809
TI  - Mycobacteria target DC-SIGN to suppress dendritic cell function.
AB  - Mycobacterium tuberculosis represents a world-wide health risk and
      immunosuppression is a particular problem in M. tuberculosis infections. Although
      macrophages are primarily infected, dendritic cells (DCs) are important in
      inducing cellular immune responses against M. tuberculosis. We hypothesized that
      DCs represent a target for M. tuberculosis and that the observed immuno
      suppression results from modulation of DC functions. We demonstrate that the DC
      specific C-type lectin DC-SIGN is an important receptor on DCs that captures and
      internalizes intact Mycobacterium bovis bacillus Calmette-Guerin (BCG) through
      the mycobacterial cell wall component ManLAM. Antibodies against DC-SIGN block M.
      bovis BCG infection of DCs. ManLAM is also secreted by M. tuberculosis-infected
      macrophages and has been implicated as a virulence factor. Strikingly, ManLAM
      binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation. Both
      mycobacteria and LPS induce DC maturation through Toll-like receptor (TLR)
      signaling, suggesting that DC-SIGN, upon binding of ManLAM, interferes with TLR
      mediated signals. Blocking antibodies against DC-SIGN reverse the ManLAM-mediated
      immunosuppressive effects. Our results suggest that M. tuberculosis targets DC
      SIGN both to infect DCs and to down-regulate DC-mediated immune responses.
      Moreover, we demonstrate that DC-SIGN has a broader pathogen recognition profile
      than previously shown, suggesting that DC-SIGN may represent a molecular target
      for clinical intervention in infections other than HIV-1.

PMID- 12515810
TI  - CD28 costimulation is required for in vivo induction of peripheral tolerance in
      CD8 T cells.
AB  - Whereas ligation of CD28 is known to provide a critical costimulatory signal for
      activation of CD4 T cells, the requirement for CD28 as a costimulatory signal
      during activation of CD8 cells is less well defined. Even less is known about the
      involvement of CD28 signals during peripheral tolerance induction in CD8 T cells.
      In this study, comparison of T cell responses from CD28-deficient and CD28 wild
      type H-Y-specific T cell receptor transgenic mice reveals that CD8 cells can
      proliferate, secrete cytokines, and generate cytotoxic T lymphocytes efficiently
      in the absence of CD28 costimulation in vitro. Surprisingly, using pregnancy as a
      model to study the H-Y-specific response of maternal T cells in the presence or
      absence of CD28 costimulation in vivo, it was found that peripheral tolerance
      does not occur in CD28KO pregnants in contrast to the partial clonal deletion and
      hyporesponsiveness of remaining T cells observed in CD28WT pregnants. These data
      demonstrate for the first time that CD28 is critical for tolerance induction of
      CD8 T cells, contrasting markedly with CD28 independence of in vitro activation,
      and suggest that the role of CD28/B7 interactions in peripheral tolerance of CD8
      T cells may differ significantly from that of CD4 T cells.

PMID- 12515811
TI  - Secondary heavy chain rearrangement: a mechanism for generating anti-double
      stranded DNA B cells.
AB  - The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely
      resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice
      by the transfer of alloreactive T cells. The availability of anti-DNA transgenes
      allows us to study the genetic origins of autoantibodies in this model. We
      induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This
      resulted in clonal expansion and selection of specific mutations in the anti
      double-stranded (ds) DNA B cell population. These data, together with a high
      frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that
      anti-dsDNAs are the product of an antigen-driven immune response. Genetic
      analysis associated this response with the generation of anti-dsDNA B cells
      through secondary rearrangements that replaced the site-directed transgene (sd
      tg) with endogenous VH genes.

PMID- 12515812
TI  - A crucial role of glycoprotein VI for platelet recruitment to the injured
      arterial wall in vivo.
AB  - Platelet adhesion and aggregation at sites of vascular injury is crucial for
      hemostasis but may lead to arterial occlusion in the setting of atherosclerosis
      and precipitate diseases such as myocardial infarction. A current hypothesis
      suggests that platelet glycoprotein (GP) Ib interaction with von Willebrand
      factor recruits flowing platelets to the injured vessel wall, where
      subendothelial fibrillar collagens support their firm adhesion and activation.
      However, so far this hypothesis has not been tested in vivo. Here, we demonstrate
      by intravital fluorescence microscopy of the mouse carotid artery that inhibition
      or absence of the major platelet collagen receptor, GPVI, abolishes platelet
      vessel wall interactions after endothelial denudation. Unexpectedly, inhibition
      of GPVI by the monoclonal antibody JAQ1 reduced platelet tethering to the
      subendothelium by approximately 89%. In addition, stable arrest and aggregation
      of platelets was virtually abolished under these conditions. Using different
      models of arterial injury, the strict requirement for GPVI in these processes was
      confirmed in GPVI-deficient mice, where platelets also failed to adhere and
      aggregate on the damaged vessel wall. These findings reveal an unexpected role of
      GPVI in the initiation of platelet attachment at sites of vascular injury and
      unequivocally identify platelet-collagen interactions (via GPVI) as the major
      determinant of arterial thrombus formation.

PMID- 12515813
TI  - Enhanced B cell expansion, survival, and humoral responses by targeting death
      receptor 6.
AB  - Targeted disruption of death receptor (DR)6 results in enhanced CD4(+) T cell
      expansion and T helper cell type 2 differentiation after stimulation. Similar to
      T cells, DR6 is expressed on resting B cells but is down-regulated upon
      activation. We examined DR6(-/-) B cell responses both in vitro and in vivo. In
      vitro, DR6(-/-) B cells undergo increased proliferation in response to anti
      immunoglobulin M, anti-CD40, and lipopolysaccharide. This hyperproliferative
      response was due, at least in part, to both increased cell division and reduced
      cell apoptosis when compared with wild-type B cells. Consistent with these
      observations, increased nuclear levels and activity of nuclear factor kappaB
      transcription factor, c-Rel, and elevated Bcl-x(l) expression were observed in
      DR6(-/-) B cells upon stimulation. In addition, DR6(-/-) B cells exhibited higher
      surface levels of CD86 upon activation and were more effective as antigen
      presenting cells in an allogeneic T cell proliferation response. DR6(-/-) mice
      exhibited enhanced germinal center formation and increased titers of
      immunoglobulins to T-dependent as well as T-independent type I and II antigens.
      This is the first demonstration of a regulatory role of DR6 in the activation and
      function of B cells.

PMID- 12515814
TI  - Critical role of the carboxyl terminus of proline-rich tyrosine kinase (Pyk2) in
      the activation of human neutrophils by tumor necrosis factor: separation of
      signals for the respiratory burst and degranulation.
AB  - Transduction of Tat-tagged fusion proteins confirmed a hypothesis based on
      pharmacologic inhibitors (Fuortes, M., M. Melchior, H. Han, G.J. Lyon, and C.
      Nathan. 1999. J. Clin. Invest. 104:327-335) that proline-rich tyrosine kinase
      (Pyk2) plays a critical role in the activation of adherent human neutrophils, and
      allowed an analysis of individual Pyk2 domains not possible with chemical
      inhibitors. Acting as a dominant negative, the COOH terminus of Pyk2 fused to a
      Tat peptide (Tat-CT), but not other regions of Pyk2, specifically inhibited the
      respiratory burst of cells responding to tumor necrosis factor (TNF), Salmonella,
      or Listeria, while sparing responses induced by phorbol ester. Tat-CT suppressed
      TNF-triggered cell spreading and the phosphorylation of endogenous Pyk2 and the
      associated tyrosine kinase Syk without blocking the ability of neutrophils to
      degranulate and kill bacteria. Thus, separate signals control the respiratory
      burst and degranulation, and a normal rate of killing of some bacteria can be
      sustained by granule products in conjunction with a minimal residual respiratory
      burst. Inhibition of select inflammatory functions without impairment of
      antibacterial activity may commend the Pyk2 pathway as a potential target for
      antiinflammatory therapy.

PMID- 12515815
TI  - Natural killer cell inhibitory receptors block actin cytoskeleton-dependent
      recruitment of 2B4 (CD244) to lipid rafts.
AB  - A dynamic balance of positive and negative signals regulates target cell lysis by
      natural killer (NK) cells upon engagement of a variety of different activation
      receptors and of inhibitory receptors that recruit the tyrosine phosphatase SHP
      1. However, the step at which activation signals are blocked by SHP-1 is not
      known. We have been using activation receptor 2B4 (CD244) to study the influence
      of inhibitory receptors on NK cell activation. Engagement of inhibitory receptors
      by HLA class I on target cells blocks phosphorylation of 2B4, placing the
      inhibitory step at the level, or upstream of 2B4 phosphorylation. Here we show
      that phosphorylated 2B4, after engagement with either antibodies or target cells
      that express the 2B4 ligand, is found exclusively in a detergent-resistant
      membrane fraction that contains lipid rafts. Integrity of lipid rafts was
      essential for phosphorylation and activating function of 2B4. Coengagement of
      inhibitory receptors blocked 2B4 phosphorylation and 2B4 association with
      detergent-resistant membranes, indicating that inhibitory receptors function
      upstream of raft-dependent signals. Recruitment of 2B4 into detergent-resistant
      membrane fractions and 2B4 phosphorylation were dependent on actin
      polymerization. Blocking actin cytoskeleton-dependent raft recruitment of
      different receptors may be a general mechanism by which inhibitory receptors
      control NK cell activation.

PMID- 12515816
TI  - Positive selection of anti-thy-1 autoreactive B-1 cells and natural serum
      autoantibody production independent from bone marrow B cell development.
AB  - A natural serum autoantibody specific for the Thy-1 glycoprotein (anti-Thy-1
      autoantibody [ATA]) is produced by B-1 cells that are positively selected by self
      antigen. Here, using ATA micro kappa transgenic mice we show that cells with this
      B cell receptor are negatively selected during bone marrow (BM) development. In a
      Thy-1 null environment, BM ATA B cells progress to a normal follicular stage in
      spleen. However, in a self-antigen-positive environment, development is arrested
      at an immature stage in the spleen, concomitant with induction of CD5. Such cells
      are tolerant and short-lived, different from B-1. Nonetheless, ATA-positive
      selection was evident by self-antigen-dependent high serum ATA production,
      comprising approximately 90% of serum immunoglobulin M in ATA micro kappa mice.
      Splenectomy did not eliminate ATA production and transfer of tolerant splenic B
      cells did not induce it. These findings demonstrate that B-1 positive selection,
      resulting in the production of natural serum ATA, arises independently from the
      major pathway of BM B cell development and selection.

PMID- 12515817
TI  - Flexibility of mouse classical and plasmacytoid-derived dendritic cells in
      directing T helper type 1 and 2 cell development: dependency on antigen dose and
      differential toll-like receptor ligation.
AB  - Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to
      direct either T helper cell (Th) type 1 or Th2 development, although more
      recently different pathogen products or stimuli have been shown to render these
      DCs more flexible. It is still unclear how distinct mouse DC subsets cultured
      from bone marrow precursors, blood, or their lymphoid tissue counterparts direct
      Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs
      (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can
      induce the development of both Th1 and Th2 effector cells depending on the dose
      of antigen. In general, high antigen doses induced Th1 cell development whereas
      low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic
      plasmacytoid-derived DCs enhanced CD4(+) T cell proliferation and induced strong
      Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand
      CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of
      plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human
      plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage
      colony-stimulating factor enhanced Th1 cell development when stimulated with LPS
      as a result of their high level of TLR4 expression. Polarized Th1 responses
      resulting from high antigen dose were not additionally enhanced by stimulation of
      DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation
      of the DCs together with the stimulation of DCs by pathogen-derived products,
      will determine whether a Th1 or Th2 response develops.

PMID- 12515818
TI  - CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent
      mechanisms.
AB  - CD4(+)CD25(+) regulatory T (T(R)) cells can inhibit a variety of autoimmune and
      inflammatory diseases, but the precise mechanisms by which they suppress immune
      responses in vivo remain unresolved. Here, we have used Helicobacter hepaticus
      infection of T cell-reconstituted recombination-activating gene (RAG)(-/-) mice
      as a model to study the ability of CD4(+)CD25(+) T(R) cells to inhibit
      bacterially triggered intestinal inflammation. H. hepaticus infection elicited
      both T cell-mediated and T cell-independent intestinal inflammation, both of
      which were inhibited by adoptively transferred CD4(+)CD25(+) T(R) cells. T cell
      independent pathology was accompanied by activation of the innate immune system
      that was also inhibited by CD4(+)CD25(+) T(R) cells. Suppression of innate immune
      pathology was dependent on T cell-derived interleukin 10 and also on the
      production of transforming growth factor beta. Thus, CD4(+)CD25(+) T(R) cells do
      not only suppress adaptive T cell responses, but are also able to control
      pathology mediated by innate immune mechanisms.

PMID- 12515819
TI  - DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic
      cells.
AB  - Early interactions between lung dendritic cells (LDCs) and Mycobacterium
      tuberculosis, the etiological agent of tuberculosis, are thought to be critical
      for mounting a protective anti-mycobacterial immune response and for determining
      the outcome of infection. However, these interactions are poorly understood, at
      least at the molecular level. Here we show that M. tuberculosis enters human
      monocyte-derived DCs after binding to the recently identified lectin DC-specific
      intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast,
      complement receptor (CR)3 and mannose receptor (MR), which are the main M.
      tuberculosis receptors on macrophages (Mphis), appeared to play a minor role, if
      any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan
      lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly
      isolated human LDCs were found to express DC-SIGN, and M. tuberculosis-derived
      material was detected in CD14(-)HLA-DR(+)DC-SIGN(+) cells in lymph nodes (LNs)
      from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV),
      which is captured by the same receptor, DC-SIGN-mediated entry of M. tuberculosis
      in DCs in vivo is likely to influence bacterial persistence and host immunity.

PMID- 12515820
TI  - Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T
      lymphocyte-associated antigen 4.
AB  - Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an essential negative
      regulator of T cell activation. Recent evidence suggests that CTLA-4 association
      with the immunological synapse during contact with antigen-presenting cells is
      important for its inhibitory function. In the present study, we observed a direct
      interaction of CTLA-4 with the phosphorylated form of T cell receptor (TCR)zeta
      within the glycolipid-enriched microdomains associated with the T cell signaling
      complex. In this setting, CTLA-4 regulated the accumulation/retention of TCRzeta
      in the signaling complex, as the lipid raft fractions from CTLA-4KO T cells
      contained significantly higher amounts of the TCR components when compared with
      wild-type littermates. In contrast, coligation of CTLA-4 with the TCR during T
      cell activation selectively decreased the amount of TCRzeta that accumulated in
      the rafts. These results suggest that CTLA-4 functions to regulate T cell
      signaling by controlling TCR accumulation and/or retention within this a critical
      component of the immunological synapse.

PMID- 12515821
TI  - Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1,
      and Sos-1.
AB  - Class I phosphoinositide 3-kinases (PI3Ks) are implicated in many cellular
      responses controlled by receptor tyrosine kinases (RTKs), including actin
      cytoskeletal remodeling. Within this pathway, Rac is a key downstream
      target/effector of PI3K. However, how the signal is routed from PI3K to Rac is
      unclear. One possible candidate for this function is the Rac-activating complex
      Eps8-Abi1-Sos-1, which possesses Rac-specific guanine nucleotide exchange factor
      (GEF) activity. Here, we show that Abi1 (also known as E3b1) recruits PI3K, via
      p85, into a multimolecular signaling complex that includes Eps8 and Sos-1. The
      recruitment of p85 to the Eps8-Abi1-Sos-1 complex and phosphatidylinositol 3, 4,
      5 phosphate (PIP3), the catalytic product of PI3K, concur to unmask its Rac-GEF
      activity in vitro. Moreover, they are indispensable for the activation of Rac and
      Rac-dependent actin remodeling in vivo. On growth factor stimulation, endogenous
      p85 and Abi1 consistently colocalize into membrane ruffles, and cells lacking p85
      fail to support Abi1-dependent Rac activation. Our results define a mechanism
      whereby propagation of signals, originating from RTKs or Ras and leading to actin
      reorganization, is controlled by direct physical interaction between PI3K and a
      Rac-specific GEF complex.

PMID- 12515822
TI  - Human centromere chromatin protein hMis12, essential for equal segregation, is
      independent of CENP-A loading pathway.
AB  - Kinetochores are the chromosomal sites for spindle interaction and play a vital
      role for chromosome segregation. The composition of kinetochore proteins and
      their cellular roles are, however, poorly understood in higher eukaryotes. We
      identified a novel kinetochore protein family conserved from yeast to human that
      is essential for equal chromosome segregation. The human homologue hMis12 of
      yeast spMis12/scMtw1 retains conserved sequence features and locates at the
      kinetochore region indistinguishable from CENP-A, a centromeric histone variant.
      RNA interference (RNAi) analysis of HeLa cells shows that the reduced hMis12
      results in misaligned metaphase chromosomes, lagging anaphase chromosomes, and
      interphase micronuclei without mitotic delay, while CENP-A is located at
      kinetochores. Further, the metaphase spindle length is abnormally extended.
      Spindle checkpoint protein hMad2 temporally localizes at kinetochores at early
      mitotic stages after RNAi. The RNAi deficiency of CENP-A leads to a similar
      mitotic phenotype, but the kinetochore signals of other kinetochore proteins,
      hMis6 and CENP-C, are greatly diminished. RNAi for hMis6, like that of a
      kinetochore kinesin CENP-E, induces mitotic arrest. Kinetochore localization of
      hMis12 is unaffected by CENP-A RNAi, demonstrating an independent pathway of CENP
      A in human kinetochores.

PMID- 12515823
TI  - A transgene carrying an A2G missense mutation in the SMN gene modulates
      phenotypic severity in mice with severe (type I) spinal muscular atrophy.
AB  - 5q spinal muscular atrophy (SMA) is a common autosomal recessive disorder in
      humans and the leading genetic cause of infantile death. Patients lack a
      functional survival of motor neurons (SMN1) gene, but carry one or more copies of
      the highly homologous SMN2 gene. A homozygous knockout of the single murine Smn
      gene is embryonic lethal. Here we report that in the absence of the SMN2 gene, a
      mutant SMN A2G transgene is unable to rescue the embryonic lethality. In its
      presence, the A2G transgene delays the onset of motor neuron loss, resulting in
      mice with mild SMA. We suggest that only in the presence of low levels of full
      length SMN is the A2G transgene able to form partially functional higher order
      SMN complexes essential for its functions. Mild SMA mice exhibit motor neuron
      degeneration, muscle atrophy, and abnormal EMGs. Animals homozygous for the
      mutant transgene are less severely affected than heterozygotes. This demonstrates
      the importance of SMN levels in SMA even if the protein is expressed from a
      mutant allele. Our mild SMA mice will be useful in (a) determining the effect of
      missense mutations in vivo and in motor neurons and (b) testing potential
      therapies in SMA.

PMID- 12515824
TI  - Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the
      mitochondrial outer membrane.
AB  - It is assumed that the survival factors Bcl-2 and Bcl-x(L) are mainly functional
      on mitochondria and therefore must contain mitochondrial targeting sequences.
      Here we show, however, that only Bcl-x(L) is specifically targeted to the
      mitochondrial outer membrane (MOM) whereas Bcl-2 distributes on several
      intracellular membranes. Mitochondrial targeting of Bcl-x(L) requires the COOH
      terminal transmembrane (TM) domain flanked at both ends by at least two basic
      amino acids. This sequence is a bona fide targeting signal for the MOM as it
      confers specific mitochondrial localization to soluble EGFP. The signal is
      present in numerous proteins known to be directed to the MOM. Bcl-2 lacks the
      signal and therefore localizes to several intracellular membranes. The COOH
      terminal region of Bcl-2 can be converted into a targeting signal for the MOM by
      increasing the basicity surrounding its TM. These data define a new targeting
      sequence for the MOM and propose that Bcl-2 acts on several intracellular
      membranes whereas Bcl-x(L) specifically functions on the MOM.

PMID- 12515825
TI  - Caspase-mediated loss of mitochondrial function and generation of reactive oxygen
      species during apoptosis.
AB  - During apoptosis, the permeabilization of the mitochondrial outer membrane allows
      the release of cytochrome c, which induces caspase activation to orchestrate the
      death of the cell. Mitochondria rapidly lose their transmembrane potential (Delta
      Psi m) and generate reactive oxygen species (ROS), both of which are likely to
      contribute to the dismantling of the cell. Here we show that both the rapid loss
      of Delta Psi m and the generation of ROS are due to the effects of activated
      caspases on mitochondrial electron transport complexes I and II. Caspase-3
      disrupts oxygen consumption induced by complex I and II substrates but not that
      induced by electron transfer to complex IV. Similarly, Delta Psi m generated in
      the presence of complex I or II substrates is disrupted by caspase-3, and ROS are
      produced. Complex III activity measured by cytochrome c reduction remains intact
      after caspase-3 treatment. In apoptotic cells, electron transport and oxygen
      consumption that depends on complex I or II was disrupted in a caspase-dependent
      manner. Our results indicate that after cytochrome c release the activation of
      caspases feeds back on the permeabilized mitochondria to damage mitochondrial
      function (loss of Delta Psi m) and generate ROS through effects of caspases on
      complex I and II in the electron transport chain.

PMID- 12515826
TI  - Amyloidogenic processing of the Alzheimer beta-amyloid precursor protein depends
      on lipid rafts.
AB  - Formation of senile plaques containing the beta-amyloid peptide (A beta) derived
      from the amyloid precursor protein (APP) is an invariant feature of Alzheimer's
      disease (AD). APP is cleaved either by beta-secretase or by alpha-secretase to
      initiate amyloidogenic (release of A beta) or nonamyloidogenic processing of APP,
      respectively. A key to understanding AD is to unravel how access of these enzymes
      to APP is regulated. Here, we demonstrate that lipid rafts are critically
      involved in regulating A beta generation. Reducing cholesterol levels in N2a
      cells decreased A beta production. APP and the beta-site APP cleavage enzyme
      (BACE1) could be induced to copatch at the plasma membrane upon cross-linking
      with antibodies and to segregate away from nonraft markers. Antibody cross
      linking dramatically increased production of A beta in a cholesterol-dependent
      manner. A beta generation was dependent on endocytosis and was reduced after
      expression of the dynamin mutant K44A and the Rab5 GTPase-activating protein, RN
      tre. This inhibition could be overcome by antibody cross-linking. These
      observations suggest the existence of two APP pools. Although APP inside raft
      clusters seems to be cleaved by beta-secretase, APP outside rafts undergoes
      cleavage by alpha-secretase. Thus, access of alpha- and beta-secretase to APP,
      and therefore A beta generation, may be determined by dynamic interactions of APP
      with lipid rafts.

PMID- 12515827
TI  - Dynamic changes in the mobility of LAT in aggregated lipid rafts upon T cell
      activation.
AB  - Lipid rafts are known to aggregate in response to various stimuli. By way of raft
      aggregation after stimulation, signaling molecules in rafts accumulate and
      interact so that the signal received at a given membrane receptor is amplified
      efficiently from the site of aggregation. To elucidate the process of lipid raft
      aggregation during T cell activation, we analyzed the dynamic changes of a raft
      associated protein, linker for activation of T cells (LAT), on T cell receptor
      stimulation using LAT fused to GFP (LAT-GFP). When transfectants expressing LAT
      GFP were stimulated with anti-CD3-coated beads, LAT-GFP aggregated and formed
      patches at the area of bead contact. Photobleaching experiments using live cells
      revealed that LAT-GFP in patches was markedly less mobile than that in nonpatched
      regions. The decreased mobility in patches was dependent on raft organization
      supported by membrane cholesterol and signaling molecule binding sites,
      especially the phospholipase C gamma 1 binding site in the cytoplasmic domain of
      LAT. Thus, although LAT normally moves rapidly at the plasma membrane, it loses
      its mobility and becomes stably associated with aggregated rafts to ensure
      organized and sustained signal transduction required for T cell activation.

PMID- 12515828
TI  - PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal
      rearrangement in cell spreading and migration.
AB  - We investigated the molecular and cellular actions of receptor protein tyrosine
      phosphatase (PTP) alpha in integrin signaling using immortalized fibroblasts
      derived from wild-type and PTP alpha-deficient mouse embryos. Defects in PTP
      alpha-/- migration in a wound healing assay were associated with altered cell
      shape and focal adhesion kinase (FAK) phosphorylation. The reduced haptotaxis to
      fibronectin (FN) of PTP alpha-/- cells was increased by expression of active (but
      not inactive) PTP alpha. Integrin-mediated formation of src-FAK and fyn-FAK
      complexes was reduced or abolished in PTP alpha-/- cells on FN, concomitant with
      markedly reduced phosphorylation of FAK at Tyr397. Reintroduction of active (but
      not inactive) PTP alpha restored FAK Tyr-397 phosphorylation. FN-induced
      cytoskeletal rearrangement was retarded in PTP alpha-/- cells, with delayed
      filamentous actin stress fiber assembly and focal adhesion formation. This
      mimicked the effects of treating wild-type fibroblasts with the src family
      protein tyrosine kinase (Src-PTK) inhibitor PP2. These results, together with the
      reduced src/fyn tyrosine kinase activity in PTP alpha-/- fibroblasts (Ponniah et
      al., 1999; Su et al., 1999), suggest that PTP alpha functions in integrin
      signaling and cell migration as an Src-PTK activator. Our paper establishes that
      PTP alpha is required for early integrin-proximal events, acting upstream of FAK
      to affect the timely and efficient phosphorylation of FAK Tyr-397.

PMID- 12515829
TI  - Ceramide in nitric oxide inhibition of glioma cell growth. Evidence for the
      involvement of ceramide traffic.
AB  - The treatment of C6 glioma cells with the nitric oxide donor, PAPANONOate ((Z)-[N
      (3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate), resulted in a dose
      dependent inhibition of cell proliferation. This was associated to a rapid and
      significant increase of ceramide levels and was mimicked by treatments that
      augment cellular ceramide. Metabolic experiments with radioactive sphingosine,
      serine, and choline showed that nitric oxide strongly reduced the utilization of
      ceramide for the biosynthesis of both sphingomyelin and glucosylceramide.
      Nevertheless, nitric oxide did not modify the activity of different enzymes of
      ceramide metabolism. The possibility that nitric oxide impairs the availability
      of ceramide for sphingolipid biosynthesis was then investigated. The metabolism
      of N-hexanoyl-[(3)H]sphingosine demonstrated that nitric oxide did not affect the
      biosynthesis of N-hexanoyl-[(3)H]sphingolipids but inhibited the metabolic
      utilization of long chain [(3)H]ceramide, synthesized in the endoplasmic
      reticulum (ER) from the recycled [(3)H]sphingosine. Moreover, results obtained
      with fluorescent ceramides, brefeldin A, ATP depletion, as well as in a ceramide
      transport assay indicate that nitric oxide impairs the traffic of ceramide from
      ER to Golgi apparatus. All this supports that, in glioma cells, the modulation of
      ceramide traffic can contribute to the regulation of its intracellular levels and
      participate in the nitric oxide-activated signaling pathway involved in the
      control of cell proliferation.

PMID- 12515830
TI  - Modulation of transforming growth factor-beta (TGF-beta) signaling by endogenous
      sphingolipid mediators.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor
      that plays a critical role in tissue repair and fibrosis. Sphingolipid signaling
      has been shown to regulate a variety of cellular processes and has been
      implicated in collagen gene regulation. The present study was undertaken to
      determine whether endogenous sphingolipids are involved in the TGF-beta signaling
      pathway. TGF-beta treatment induced endogenous ceramide levels in a time
      dependent manner within 5-15 min of cell stimulation. Using human fibroblasts
      transfected with a alpha2(I) collagen promoter/reporter gene construct (COL1A2),
      C(6)-ceramide (10 microm) exerted a stimulatory effect on basal and TGF-beta
      induced activity of this promoter. Next, to define the effects of endogenous
      sphingolipids on TGF-beta signaling we employed ectopic expression of enzymes
      involved in sphingolipid metabolism. Sphingosine 1-phosphate phosphatase (YSR2)
      stimulated basal COL1A2 promoter activity and cooperated with TGF-beta in
      activation of this promoter. Furthermore, overexpression of YSR2 resulted in the
      pronounced increase of COL1A1 and COL1A2 mRNA levels. Conversely, overexpression
      of sphingosine kinase (SPHK1) inhibited basal and TGF-beta-stimulated COL1A2
      promoter activity. These results suggest that endogenous ceramide, but not
      sphingosine or sphingosine 1-phosphate, is a positive regulator of collagen gene
      expression. Mechanistically, we demonstrate that Smad3 is a target of YSR2. TGF
      beta-induced Smad3 phosphorylation was elevated in the presence of YSR2.
      Cotransfection of YSR2 with wild-type Smad3, but not with the phosphorylation
      deficient mutant of Smad3 (Smad3A), resulted in a dramatic increase of COL1A2
      promoter activity. In conclusion, this study demonstrates a direct role for the
      endogenous sphingolipid mediators in regulating the TGF-beta signaling pathway.

PMID- 12515831
TI  - Protein engineering of the tissue inhibitor of metalloproteinase 1 (TIMP-1)
      inhibitory domain. In search of selective matrix metalloproteinase inhibitors.
AB  - Studies of the structural basis of the interactions of tissue inhibitors of
      metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) may provide clues
      for designing MMP-specific inhibitors. In this paper we report combinations of
      mutations in the major MMP-binding region that enhance the specificity of N-TIMP
      1. Mutants with substitutions for residues 4 and 68 were characterized and
      combined with previously studied Thr(2) mutations to generate mutants with
      improved selectivity or binding affinity to specific MMPs. Some combinations of
      mutations had non-additive effects on DeltaG of binding to MMPs, suggesting
      interactions between subsites in the reactive site. The T2L/V4S mutation
      generates an inhibitor that binds to MMP-2 20-fold more tightly than to MMP
      3(DeltaC) and over 400-fold more tightly than to MMP-1. The T2S/V4A/S68Y mutant
      is the strongest inhibitor for stromelysin-1 among all mutants characterized to
      date, with an apparent K(i) for MMP-3(DeltaC) in the picomolar range. A third
      mutant, T2R/V4I, has no detectable inhibitory activity for MMP-1 but is an
      effective inhibitor of MMP-2 and -3. These selective TIMP variants may provide
      useful tools for investigation of biological roles of specific MMPs and for
      possible therapy of MMP-related diseases.

PMID- 12515832
TI  - The future of behavioral health and primary care: drowning in the mainstream or
      left on the bank?

PMID- 12515833
TI  - Clinical experience with the management of schizophrenia in the general hospital.
AB  - On the basis of experience with 74 psychiatric consultations involving patients
      with schizophrenia admitted to a general hospital medical or surgical ward over a
      17-month period (3% of the psychiatric consultations during that period), the
      authors identified 10 types of problems leading to requests for consultation. The
      authors used these categories to organize recommendations for management of
      patients with schizophrenia in the general medical hospital. In addition to
      conducting conventional consultations, the consultation psychiatrist in such
      cases often has a role in educating hospital staff about schizophrenia and in
      serving as a physician for the mentally ill.

PMID- 12515834
TI  - Depression as a prognostic factor for breast cancer mortality.
AB  - It is unclear if depression or depressive symptoms have an effect on mortality in
      breast cancer patients. In this population-based, nationwide, retrospective
      cohort study in Denmark, depression was defined as affective or anxiety disorders
      that necessitated psychiatric hospital admission. All the affective and anxiety
      disorders were divided and categorized into five ordinal diagnostic groups. Early
      stage (N=10382) and late-stage (N=10211) breast cancer patients were analyzed
      separately with Cox's regression adjusted for well-documented somatic prognostic
      variables. The authors used survival analysis of data from three central
      registers and found that breast cancer patients with depression had a modestly
      but significantly higher risk of mortality depending on stage of breast cancer
      and time of depression. The same result was found after censoring unnatural
      causes of death such as accident, suicide, or homicide.

PMID- 12515835
TI  - The clinical significance of major depression following mild traumatic brain
      injury.
AB  - OBJECTIVE: The authors assessed the association of major depression with
      behavioral outcome following mild traumatic brain injury. METHOD: Consecutive
      patients with mild traumatic brain injury (N=170) were assessed for major
      depression. Those with major depression were compared with those without on self
      report measures of psychosocial dysfunction, psychological distress, and
      postconcussive symptoms in addition to examiner-rated neurobehavioral
      disturbance. RESULTS: Major depression was seen in 15.3% (N=26) of the subjects
      after traumatic brain injury, and these individuals showed subjective and
      objective evidence of poorer outcome. CONCLUSIONS: Major depression is associated
      with poor outcome across multiple domains. This study highlights the need for the
      early diagnosis and prompt treatment of major depression following mild traumatic
      brain injury.

PMID- 12515836
TI  - A pilot randomized controlled trial of dexamphetamine in patients with chronic
      fatigue syndrome.
AB  - This study determined whether dexamphetamine improved symptoms and quality of
      life in patients with chronic fatigue syndrome. The setting was a specialized
      clinic within a tertiary referral hospital. This was a 6-week parallel-group,
      placebo-controlled trial with random allocation. There was a 2-week dose
      adjustment phase and a 4-week stable treatment period. Outcome measures were the
      Fatigue Severity Scale, the Medical Outcomes Study 36-item Short-Form Health
      Survey, and two patient-determined outcomes. Ten patients were randomly assigned
      to dexamphetamine, and 10 were assigned to placebo. Fatigue Severity Scale scores
      improved in nine of 10 dexamphetamine and four of 10 placebo patients. The change
      in mean score was statistically significant. There were large but statistically
      nonsignificant changes in scores for the Short-Form Health Survey domains
      vitality and physical functioning. Dexamphetamine may be useful in the management
      of chronic fatigue syndrome; a larger and longer trial is justified by these
      results.

PMID- 12515837
TI  - Randomized trial of cognitive behavior therapy versus supportive psychotherapy
      for HIV-related peripheral neuropathic pain.
AB  - The feasibility and acceptability of cognitive behavior therapy for HIV-related
      peripheral neuropathic pain was examined and the potential efficacy of the
      intervention was compared with that of supportive psychotherapy in reducing pain,
      pain-related interference with functioning, and distress. Sixty-one patients were
      randomly assigned to receive six weekly sessions of cognitive behavior therapy or
      supportive psychotherapy. Thirty-three subjects completed the protocol. Both
      groups showed significant reductions in pain. The cognitive behavior group
      improved in most domains of pain-related functional interference and distress;
      the supportive psychotherapy group showed fewer gains. The high dropout rate
      suggests that psychotherapeutic treatments for HIV-related pain may have limited
      feasibility and acceptability.

PMID- 12515838
TI  - Relationship of functional quality of life to strategies for coping with the
      stress of living with HIV/AIDS.
AB  - The authors examined factors associated with four dimensions of functional
      quality of life (physical functioning, energy/fatigue, social functioning, and
      role functioning) in 142 men and women living with HIV/AIDS. Participants
      completed the Brief COPE inventory and the Medical Outcomes Study Health Survey,
      with HIV-relevant items added. Greater use of maladaptive coping strategies was
      associated with lower levels of energy and social functioning. Pain severe enough
      to interfere with daily living tasks was associated with a lower level of
      functional quality of life on all four quality of life dimensions. Interventions
      aimed at developing adaptive coping strategies and improving pain management may
      improve functional aspects of quality of life in persons living with HIV/AIDS.

PMID- 12515839
TI  - Symptoms of pain and depression in related marrow donors: changes after
      transplant.
AB  - Related or unrelated histocompatible marrow donors make it possible to offer
      hematopoietic stem cell transplants, the second most frequent solid organ
      transplant performed in the United States. About 20%-30% of donors are related to
      the recipient. Despite their importance, relatively little is known about related
      donors. The purpose of this prospective study is to describe changes in pain and
      depressive symptoms in 23 related marrow donors before and after marrow donation.
      Approximately 6 months after marrow donation, related marrow donors whose
      recipients died had significantly higher Beck Depression Inventory scores than
      did donors whose related recipients were living.

PMID- 12515840
TI  - Acute psychiatric manifestations of stroke: a clinical case conference.

PMID- 12515841
TI  - Worsening of symptoms of bulimia nervosa during pregnancy.

PMID- 12515842
TI  - Alcohol withdrawal in severe hypothyroidism.

PMID- 12515843
TI  - Rectal carcinoma with dementia.

PMID- 12515844
TI  - Olanzapine and haloperidol: potential for neutropenia?

PMID- 12515845
TI  - Postnatal polydipsia.

PMID- 12515846
TI  - Delirium associated with gatifloxacin.

PMID- 12515847
TI  - Psychiatric symptoms after hepatic resection.

PMID- 12515851
TI  - Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of
      cortical neurons in the developing brain.
AB  - The present study stems from our previous observations that the brains of adult
      estrogen receptor beta knockout (ERbeta-/-) mice show regional neuronal
      hypocellularity especially in the cerebral cortex. We now show that ERbeta is
      necessary for late embryonic development of the brain and is involved in both
      neuronal migration and apoptosis. At embryonic day (E)18.5, ERbeta-/- mouse
      brains were smaller than those of the wild-type (WT) littermates, and there were
      fewer neurons in the cortex. There were no differences in size or cellularity at
      E14.5. When proliferating cells were labeled with 5'-bromodeoxyuridine (BrdUrd)
      on E12.5, a time when cortical neurogenesis in mice begins, and examined on
      E14.5, there was no difference between WT and ERbeta-/- mice in the number of
      labeled cells in the cortex. However, when BrdUrd was administered between E14.5
      and E16.5, a time when postmitotic neurons migrate to layers of the cortex, there
      were fewer BrdUrd-labeled cells in the superficial cortical layers by E18.5 and
      postnatal day 14 in mice lacking ERbeta. At E18.5, there were more apoptotic
      cells in the ventricular zone of mice lacking ERbeta. In addition, the processes
      of the cortical radial glia, which are essential for guiding the migrating
      neurons, were fragmented. These findings suggest that by influencing migration
      and neuronal survival, ERbeta has an important role in brain development.

PMID- 12515852
TI  - Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl
      cotransporter is inhibited by wild-type but not mutant WNK4.
AB  - Mutations in the serine-threonine kinases WNK1 and WNK4 [with no lysine (K) at a
      key catalytic residue] cause pseudohypoaldosteronism type II (PHAII), a Mendelian
      disease featuring hypertension, hyperkalemia, hyperchloremia, and metabolic
      acidosis. Both kinases are expressed in the distal nephron, although the
      regulators and targets of WNK signaling cascades are unknown. The Cl(-)
      dependence of PHAII phenotypes, their sensitivity to thiazide diuretics, and the
      observation that they constitute a "mirror image" of the phenotypes resulting
      from loss of function mutations in the thiazide-sensitive Na-Cl cotransporter
      (NCCT) suggest that PHAII may result from increased NCCT activity due to altered
      WNK signaling. To address this possibility, we measured NCCT-mediated Na(+)
      influx and membrane expression in the presence of wild-type and mutant WNK4 by
      heterologous expression in Xenopus oocytes. Wild-type WNK4 inhibits NCCT-mediated
      Na-influx by reducing membrane expression of the cotransporter ((22)Na-influx
      reduced 50%, P < 1 x 10(-9), surface expression reduced 75%, P < 1 x 10(-14) in
      the presence of WNK4). This inhibition depends on WNK4 kinase activity, because
      missense mutations that abrogate kinase function prevent this effect. PHAII
      causing missense mutations, which are remote from the kinase domain, also prevent
      inhibition of NCCT activity, providing insight into the pathophysiology of the
      disorder. The specificity of this effect is indicated by the finding that WNK4
      and the carboxyl terminus of NCCT coimmunoprecipitate when expressed in HEK 293T
      cells. Together, these findings demonstrate that WNK4 negatively regulates
      surface expression of NCCT and implicate loss of this regulation in the molecular
      pathogenesis of an inherited form of hypertension.

PMID- 12515853
TI  - A photocleavable fluorescent nucleotide for DNA sequencing and analysis.
AB  - DNA sequencing by synthesis during a polymerase reaction using laser-induced
      fluorescence detection is an approach that has a great potential to increase the
      throughput and data quality of DNA sequencing. We report the design and synthesis
      of a photocleavable fluorescent nucleoside triphosphate, one of the essential
      molecules required for the sequencing-by-synthesis approach. We synthesized this
      nucleoside triphosphate by attaching a fluorophore, 4,4-difluoro-5,7-dimethyl-4
      bora-3alpha,4alpha-diaza-s-indacene propionic acid (BODIPY), to the 5 position of
      2'-deoxyuridine triphosphate via a photocleavable 2-nitrobenzyl linker. We
      demonstrate that the nucleotide analogue can be faithfully incorporated by a DNA
      polymerase Thermo Sequenase into the growing DNA strand in a DNA-sequencing
      reaction and that its incorporation does not hinder the addition of the
      subsequent nucleotide. These results indicate that the nucleotide analogue is an
      excellent substrate for Thermo Sequenase. We also systematically studied the
      photocleavage of the fluorescent dye from a DNA molecule that contained the
      nucleotide analogue. UV irradiation at 340 nm of the DNA molecule led to the
      efficient release of the fluorescent dye, ensuring that a previous fluorescence
      signal did not leave any residue that could interfere with the detection of the
      next nucleotide. Thus, our results indicate that it should be feasible to use
      four different fluorescent dyes with distinct fluorescence emissions as unique
      tags to label the four nucleotides (A, C, G, and T) through the photocleavable 2
      nitrobenzyl linker. These fluorescent tags can be removed easily by photocleavage
      after the identification of each nucleotide in the DNA sequencing-by-synthesis
      approach.

PMID- 12515854
TI  - Photocleavage of a 2-nitrobenzyl linker bridging a fluorophore to the 5' end of
      DNA.
AB  - Three single-stranded DNA molecules of different lengths were synthesized and
      characterized, each containing a fluorescent dye (6-carboxyfluorescein) connected
      to the 5' end via a photocleavable 2-nitrobenzyl linker and a biotin moiety at
      the 3' end. UV irradiation (lambda approximately 340 nm) of solutions containing
      these fluorescent DNA molecules caused the complete cleavage of the nitrobenzyl
      linker, separating the fluorophore from the DNA. The photocleavage products were
      characterized by HPLC and matrix-assisted laser desorption ionization/time-of
      flight mass spectrometry. Our experimental results indicated that the proximity
      of the chromophore 6-carboxyfluorescein to the 2-nitrobenzyl linker did not
      hinder the quantitative photocleavage of the linker in the DNA molecules. The
      biotin moiety allowed immobilization of the fluorescent DNA on streptavidin
      coated glass chips. The photocleavage of the immobilized DNA was investigated
      directly by fluorescence spectroscopy. The results demonstrated that close to 80%
      of the fluorophore was removed from the immobilized DNA after UV irradiation at
      340 nm. These results strongly support the application of the 2-nitrobenzyl
      moiety as an efficient photocleavable linker, connecting fluorescent probes to
      DNA molecules for a variety of biological analyses such as DNA sequencing by
      synthesis.

PMID- 12515855
TI  - Permissive corridor and diffusible gradients direct medial ganglionic eminence
      cell migration to the neocortex.
AB  - Young neurons born in the medial ganglionic eminence (MGE) migrate a long
      distance dorsally, giving rise to several types of interneurons in neocortex. The
      mechanisms that facilitate selective dorsal dispersion of MGE cells while
      restricting their movement ventrally into neighboring regions are not known.
      Using microtransplantation into fetal brain slices and onto dissociated substrate
      cells on floating filters (spot assay), we demonstrate that ventral forebrain
      regions neighboring the MGE are nonpermissive for MGE cell migration, whereas the
      dorsal regions leading to the neocortex are increasingly permissive. Spot assay
      experiments using filters with different pore sizes indicate that the permissive
      factors are not diffusible. We also show that MGE cells respond to
      chemoattractive and inhibitory factors diffusing from the neocortex and
      ventromedial forebrain, respectively. We propose that the final extent and
      regional specificity of MGE cell dispersion is largely dictated by contact
      guidance through a selectively permissive environment, flanked by nonpermissive
      tissues. In addition, we propose that chemotactic guidance cues superimposed over
      the permissive corridor facilitate efficient dorsal migration of MGE cells.

PMID- 12515856
TI  - Self-consistent determination of the transition state for protein folding:
      application to a fibronectin type III domain.
AB  - We present a general approach in which theory and experiments are combined in an
      iterative manner to provide a detailed description of the transition state
      ensemble (TSE) for folding. The method is illustrated by applying it to TNfn3, a
      fibronectin type III domain protein. In the first iteration, a coarse-grained
      determination of the TSE is carried out by using a limited set of experimental
      phi values as constraints in a molecular dynamics sampling simulation. The
      resulting model of the TSE is used to determine the additional residues whose phi
      value measurement would provide the most information for refining the TSE.
      Successive iterations with an increasing number of phi value measurements are
      carried out until no further changes in the properties of the TSE are detected or
      there are no additional residues whose phi values can be measured. In the study
      of TNfn3 three iterations were necessary to achieve self-consistency. A
      retrospective application of the method can be used to determine the accuracy of
      the TSE results and to find "key residues" for folding, i.e., those that are most
      important for the formation of the TSE. The approach reported here is an
      efficient method for finding the structures that make up the TSEs for protein
      folding. Its use will improve future efforts for their experimental determination
      and refinement.

PMID- 12515857
TI  - A monoclonal antibody recognizing human cancers with amplification/overexpression
      of the human epidermal growth factor receptor.
AB  - Epidermal growth factor receptor (EGFR) has attracted considerable attention as a
      target for cancer therapy. Wild-type (wt)EGFR is amplified/overexpressed in a
      number of tumor types, and several mutant forms of the coding gene have been
      found, with DeltaEGFR, a deletion mutation lacking exons 2-7 of the external
      domain, being the most common and particularly associated with glioblastoma. We
      generated monoclonal antibodies (mAbs) against NR6(DeltaEGFR) (mouse fibroblast
      line NR6 transfected with DeltaEGFR). mAb 806 with selective reactivity for
      NR6(DeltaEGFR) in mixed hemadsorption assays, fluorescence-activated cell
      sorting, Western blot, and immunohistochemistry was analyzed in detail and
      compared with mAbs 528 (anti-wtEGFR) and DH8.3 (anti-DeltaEGFR). In xenograft
      tumors and molecularly pretyped glioblastomas, the reactivity pattern was as
      follows: 528 reactive with amplified and nonamplified wtEGFR; DH8.3 reactive with
      DeltaEGFR; and 806 reactive with amplified/overexpressed wtEGFR (with or without
      DeltaEGFR). In normal tissues, 528 but not DH8.3 or 806 was widely reactive with
      many organs, e.g., liver expressing high EGFR levels. In glioblastoma and non-CNS
      tumor panels, 806 was reactive with a high proportion of glioblastomas and a
      substantial number of epithelial cancers of lung and of head and neck. DH8.3
      reactivity was restricted to DeltaEGFR-positive glioblastoma. Thus, 806
      represents a category of mAbs that recognizes tumors with EGFR
      amplification/overexpression but not normal tissues or tumors with normal EGFR
      levels. Our study also indicates that DeltaEGFR is restricted to glioblastoma, in
      contrast to other reports that this mutation is found in tumors outside the
      brain.

PMID- 12515858
TI  - Interstice mutations that block site-to-site translocation of a misactivated
      amino acid bound to a class I tRNA synthetase.
AB  - Class I aminoacyl-tRNA synthetases catalyze editing reactions that prevent
      ambiguity from entering the genetic code. Misactivated amino acids are
      translocated in cis from the active site for aminoacylation to the center for
      editing, located approximately 30 A away. Mutational analysis has functionally
      separated the two sites by creating mutations that disrupt the catalytic center
      for editing but not for aminoacylation and vice versa. What is not known is
      whether translocation per se can be disrupted without an effect on either
      catalytic center. Here we describe mutations in a presumptive "hinge region" of
      isoleucyl-tRNA synthetase that is situated between the two sites. Interstice
      mutations had little or no effect on either catalytic center. In contrast, the
      same specific mutations disrupted translocation. Thus, with these mutations all
      three functions, translocation, catalysis of aminoacylation, and editing, have
      been mutationally separated. The results are consistent with translocation
      involving a hinge-region conformational shift that does not perturb the two
      catalytic centers.

PMID- 12515859
TI  - Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate
      ubiquinone oxidoreductase).
AB  - Enzymes in the mitochondrial respiratory chain are involved in various
      physiological events in addition to their essential role in the production of ATP
      by oxidative phosphorylation. The use of specific and potent inhibitors of
      complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c
      reductase), such as rotenone and antimycin, respectively, has allowed
      determination of the role of these enzymes in physiological processes. However,
      unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and
      specific inhibitors of complex II (succinate-ubiquinone reductase) that have been
      described. In this article, we report that atpenins potently and specifically
      inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II.
      Therefore, atpenins may be useful tools for clarifying the biochemical and
      structural properties of complex II, as well as for determining its physiological
      roles in mammalian tissues.

PMID- 12515860
TI  - Dual roles of modulatory calcineurin-interacting protein 1 in cardiac
      hypertrophy.
AB  - The calcium/calmodulin-dependent protein phosphatase calcineurin stimulates
      cardiac hypertrophy in response to numerous stimuli. Calcineurin activity is
      suppressed by association with modulatory calcineurin-interacting protein
      (MCIP)1DSCR1, which is up-regulated by calcineurin signaling and has been
      proposed to function in a negative feedback loop to modulate calcineurin
      activity. To investigate the involvement of MCIP1 in cardiac hypertrophy in vivo,
      we generated MCIP1 null mice and subjected them to a variety of stress stimuli
      that induce cardiac hypertrophy. In the absence of stress, MCIP1(-/-) animals
      exhibited no overt phenotype. However, the lack of MCIP1 exacerbated the
      hypertrophic response to activated calcineurin expressed from a muscle-specific
      transgene, consistent with a role of MCIP1 as a negative regulator of calcineurin
      signaling. Paradoxically, however, cardiac hypertrophy in response to pressure
      overload or chronic adrenergic stimulation was blunted in MCIP1(-/-) mice. These
      findings suggest that MCIP1 can facilitate or suppress cardiac calcineurin
      signaling depending on the nature of the hypertrophic stimulus. These opposing
      roles of MCIP have important implications for therapeutic strategies to regulate
      cardiac hypertrophy through modulation of calcineurin-MCIP activity.

PMID- 12515861
TI  - The Euler-Maclaurin formula for simple integral polytopes.
AB  - We give a Euler-Maclaurin formula with remainder for the sum of a smooth function
      on the integral points in a simple integral lattice polytope. Our proof uses
      elementary methods.

PMID- 12515862
TI  - Bimodal signal requisite for agonistic behavior in a dart-poison frog,
      Epipedobates femoralis.
AB  - Animal acoustic signals play seminal roles in mate attraction and regulation of
      male spacing, maintenance of pairbonds, localization of hosts by parasites, and
      feeding behavior. Among vertebrate signals, it is becoming clear that no single
      stereotyped signal feature reliably elicits species-specific behavior, but
      rather, that a suite of characters is involved. Within the largely nocturnal
      clade of anuran amphibians, the dart-poison frog, Epipedobates femoralis, is a
      diurnal species that physically and vigorously defends its calling territory
      against conspecific intruders. Here we report that physical attacks by a
      territorial male are provoked only in response to dynamic bimodal stimuli in
      which the acoustic playback of vocalizations is coupled with vocal sac
      pulsations, but not by either unimodal cues presented in isolation or static
      bimodal stimuli. These results suggest that integration of dynamic bimodal cues
      is necessary to elicit aggression in this species.

PMID- 12515863
TI  - Visualization of coupled protein folding and binding in bacteria and purification
      of the heterodimeric complex.
AB  - During overexpression of recombinant proteins in Escherichia coli, misfolded
      proteins often aggregate and form inclusion bodies. If an aggregation-prone
      recombinant protein is fused upstream (as an N-terminal fusion) to GFP,
      aggregation of the recombinant protein domain also leads to misfolding of the
      downstream GFP domain, resulting in a decrease or loss of fluorescence. We
      investigated whether the GFP domain could fold correctly if aggregation of the
      upstream protein domain was prevented in vivo by a coupled protein folding and
      binding interaction. Such interaction has been previously shown to occur between
      the E. coli integration host factors alpha and beta, and between the domains of
      the general transcriptional coactivator cAMP response element binding protein
      (CREB)-binding protein and the activator for thyroid hormone and retinoid
      receptors. In this study, fusion of integration host factor beta or the CREB
      binding protein domain upstream to GFP resulted in aggregation of the fusion
      protein. Coexpression of their respective partners, on the other hand, allowed
      soluble expression of the fusion protein and a dramatic increase in fluorescence.
      The study demonstrated that coupled protein folding and binding could be
      correlated to GFP fluorescence. A modified miniintein containing an affinity tag
      was inserted between the upstream protein domain and GFP to allow rapid
      purification and identification of the heterodimeric complex. The GFP
      coexpression fusion system may be used to identify novel protein-protein
      interactions that involve coupled folding and binding or protein partners that
      can solubilize aggregation-prone recombinant proteins.

PMID- 12515864
TI  - Rare earth-doped glass microbarcodes.
AB  - The development of ultraminiaturized identification tags has applications in
      fields ranging from advanced biotechnology to security. This paper describes
      micrometer-sized glass barcodes containing a pattern of different fluorescent
      materials that are easily identified by using a UV lamp and an optical
      microscope. A model DNA hybridization assay using these "microbarcodes" is
      described. Rare earth-doped glasses were chosen because of their narrow emission
      bands, high quantum efficiencies, noninterference with common fluorescent labels,
      and inertness to most organic and aqueous solvents. These properties and the
      large number (>1 million) of possible combinations of these microbarcodes make
      them attractive for use in multiplexed bioassays and general encoding.

PMID- 12515865
TI  - Evidence that exposure of the telomere 3' overhang sequence induces senescence.
AB  - Normal human cells cease proliferation after a finite number of population
      doublings, a phenomenon termed replicative senescence. This process, first
      convincingly described by Hayflick and Moorhead [Hayflick, L. & Moorhead, P. S.
      (1961) Exp. Cell Res. 25, 595-621] for cultured human fibroblasts 40 years ago,
      is suggested to be a fundamental defense against cancer. Several events have been
      demonstrated to induce the senescent phenotype including telomere shortening, DNA
      damage, oxidative stress, and oncogenic stimulation. The molecular mechanisms
      underlying senescence are poorly understood. Here we report that a 1-week
      exposure to oligonucleotide homologous to the telomere 3'-overhang sequence
      TTAGGG (T-oligo) similarly specifically induces a senescent phenotype in cultured
      human fibroblasts, mimicking serial passage or ectopic expression of a dominant
      negative form of the telomeric repeat binding factor, TRF2(DN). We propose that
      exposure of the 3' overhang due to telomere loop disruption may occur with
      critical telomere shortening or extensive acute DNA damage and that the exposed
      TTAGGG tandem repeat sequence then triggers DNA-damage responses. We further
      demonstrate that these responses can be induced by treatment with
      oligonucleotides homologous to the overhang in the absence of telomere
      disruption, a phenomenon of potential therapeutic importance.

PMID- 12515866
TI  - Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia
      associated RhoGEF.
AB  - Heterotrimeric G proteins, G12 and G13, have been shown to transduce signals from
      G protein-coupled receptors to activate Rho GTPase in cells. Recently, we
      identified p115RhoGEF, one of the guanine nucleotide exchange factors (GEFs) for
      Rho, as a direct link between Galpha13 and Rho [Kozasa, T., et al. (1998) Science
      280, 2109-2111; Hart, M. J., et al. (1998) Science 280, 2112-2114]. Activated
      Galpha13 stimulated the RhoGEF activity of p115 through interaction with the N
      terminal RGS domain. However, Galpha12 could not activate Rho through p115,
      although it interacted with the RGS domain of p115. The biochemical mechanism
      from Galpha12 to Rho activation remained unknown. In this study, we analyzed the
      interaction of leukemia-associated RhoGEF (LARG), which also contains RGS domain,
      with Galpha12 and Galpha13. RGS domain of LARG demonstrated Galpha12- and
      Galpha13-specific GAP activity. LARG synergistically stimulated SRF activation by
      Galpha12 and Galpha13 in HeLa cells, and the SRF activation by Galpha12-LARG was
      further stimulated by coexpression of Tec tyrosine kinase. It was also found that
      LARG is phosphorylated on tyrosine by Tec. In reconstitution assays, the RhoGEF
      activity of nonphosphorylated LARG was stimulated by Galpha13 but not Galpha12.
      However, when LARG was phosphorylated by Tec, Galpha12 effectively stimulated the
      RhoGEF activity of LARG. These results demonstrate the biochemical mechanism of
      Rho activation through Galpha12 and that the regulation of RhoGEFs by
      heterotrimeric G proteins G1213 is further modulated by tyrosine phosphorylation.

PMID- 12515867
TI  - Room temperature measurements of the 3D orientation of single CdSe quantum dots
      using polarization microscopy.
AB  - Simple far-field emission polarization microscopy reveals that the emission
      transition dipole of CdSe colloidal quantum dots (QDs) is twofold degenerate at
      room temperature. We measure, model, and compare polarization anisotropy
      statistics of CdSe QDs and DiI (a one-dimensional emitter). We find excellent
      agreement between experiment and theory if the transition dipole of CdSe QDs is
      assumed to be twofold degenerate. This implies that the three-dimensional
      orientation of the unique crystal axis in QDs can be determined at room
      temperature with polarization microscopy. We describe an optical setup to measure
      four polarization angles of multiple single QDs simultaneously and in real time
      (approximately equal to 16 Hz). We use this setup in a proof-of-concept
      experiment to demonstrate that the rotational motion of QDs can be monitored in
      various host matrices.

PMID- 12515868
TI  - Long-term efficacy of high-activity 111in-pentetreotide therapy in patients with
      disseminated neuroendocrine tumors.
AB  - High-activity (111)In-pentetreotide has been used to treat patients with
      disseminated neuroendocrine tumors. There is, however, little information related
      to the efficacy of this agent beyond the normal 6-mo assessment period. Before we
      can assume that such treatment would be beneficial to patients with
      neuroendocrine tumors the outcome of the patients over a longer time course
      should be determined. METHODS: The case records of 16 patients who had received
      high activities of (111)In-pentetreotide (with cumulative activities as high as
      36.6 GBq) over a 2.5-y period, from January 1, 1997, to June 30, 2000, were
      reviewed. There were 8 female and 8 male patients (age range, 32-76 y): 10
      patients had carcinoid, 2 had medullary cell carcinoma of the thyroid, and 1 each
      had a gastrinoma, glucagonoma, fibrolamellar cancer, and malignant histiocytoma.
      The minimum number of treatments received was 1 in 2 patients (with activities of
      3.1 and 7 GBq); the maximum was 10 treatments (total, 36.6 GBq). Treatment was
      given using an infusion pump and was repeated at 4- to 12-wk intervals (mean
      number of treatments per patient, 6). Response to therapy was determined by
      changes in the size of the tumor on CT using the response evaluation criteria in
      solid tumors. Toxicity was measured using blood and urine tests of renal,
      hepatic, thyroid, and bone marrow function. The mean and median time from the
      last treatment to progression of disease and death (if applicable) was also
      calculated. RESULTS: No significant or long-lasting toxicity was encountered. At
      6 mo after the patient's last treatment, 5 patients (30%) had disease
      progression, 2 had complete responses, and 3 had partial responses. Twelve months
      after their last treatment, 9 patients (56%) had disease progression, and, at 18
      mo, 11 patients (69%) had disease progression. The mean progression-free survival
      was 12.25 mo (median, 9 mo). For those who survived 6 mo after their last
      treatment, the mean survival was 15.75 mo (median, 16 mo). At the 6-mo assessment
      point, there had been 3 deaths (19%): 1 death was not related to cancer. At 12
      mo, there was 1 additional cancer death. At 18 mo, there were 3 additional deaths
      (1 was not related to the patient's carcinoid tumor but was due to a second
      coexistent cancer). By the end of the 18-mo assessment period, 7 patients (44%)
      had died. The mean time interval between disease progression and death was 5 mo.
      CONCLUSION: In patients treated with high-activity (111)In-pentreotide, 70% had
      some benefit for at least 6 mo after the end of treatment; however, 31% of
      patients will have sustained benefit at 18 mo from this treatment. This was
      obtained without significant toxicity.

PMID- 12515869
TI  - Retrospective analysis of sentinel node localization in multifocal, multicentric,
      palpable, or nonpalpable breast cancer.
AB  - Multicentric or multifocal breast cancer is considered as one of the limitations
      for sentinel lymph node (SLN) localization. We did a retrospective analysis to
      evaluate the success rate, sensitivity, accuracy, and negative predictive values
      of SLN localization in multicentric or multifocal breast lesions. METHODS: Fifty
      nine patients with multifocal or multicentric breast lesions proven by either
      fine-needle aspiration (19/59), core biopsy (39/59), or lumpectomy (8/59)
      underwent SLN localization. Of these patients, 46 had SLN localization by both
      radiocolloid and blue dye, and 13 had SLN localization by radiocolloid alone.
      Approximately 10 MBq (99m)Tc-labeled unfiltered sulfur colloid in 0.3-0.4 mL were
      injected intradermally over the 1 or 2 breast tumor locations 2-4 h before
      surgery. During surgery, vital blue dye was injected intraparenchymally in 4-6
      places around the tumor. All lymph nodes with counts of >10 times that of the
      background counts, whether or not blue dye positive, and all blue dye-positive
      lymph nodes, whether or not radiocolloid positive, were excised and labeled
      accordingly. All lymph nodes underwent frozen sectioning and were examined by
      hematoxylin and eosin and immunohistologic (cytokeratin) staining. RESULTS: Of
      the 59 patients, 48 had axillary lymph node dissection irrespective of the
      results of pathologic examination of the SLN. The success rate, sensitivity,
      negative predictive value, and accuracy were 93%, 100%, 100%, and 100% using the
      radiocolloid probe, 87%, 100%, 100%, and 100% using blue dye, and 93.5%, 100%,
      100%, and 100% using combined methods, respectively. Concordance between blue dye
      and radiocolloid was 91% (the incidence of the number of sentinel nodes detected
      was 37.5%, 30.3%, 10.7%, and 21.4% for 1, 2, 3, and 4 or more lymph nodes,
      respectively). Metastatic lymph node involvement was found in 39.5% of patients.
      CONCLUSION: The sentinel node localization approach showed a high negative
      predictive value in breast cancer patients with multifocal or multicentric
      lesions, contrary to the common belief of significant false-negative results in
      these patients.

PMID- 12515870
TI  - Mechanism of accumulation of 99mTc-sulesomab in inflammation.
AB  - 99mTc-Sulesomab, the Fab fragment of anti-NCA-90, is used as an in vivo
      granulocyte labeling agent for imaging inflammation. It is not clear to what
      extent it targets cells that have already migrated into the interstitial space of
      an inflammatory lesion as opposed to circulating cells. The contribution to
      signal of radioprotein diffusion in the setting of increased vascular
      permeability is also poorly documented. METHODS: We compared the local kinetics
      of (99m)Tc-sulesomab and (99m)Tc-labeled human serum albumin (HSA), which have
      similar molecular sizes, in 7 patients with orthopedic infection proven by
      clearly positive (111)In-leukocyte scintigraphy. (99m)Tc-Sulesomab and (99m)Tc
      HSA were administered in sequence separated by an interval of 2-6 d. Images were
      obtained 1, 3, 4, and 6 h after injection, and multiple venous blood samples were
      obtained for blood clearance measurement. Patlak-Rutland (P-R) analysis was
      performed to measure lesion and control tissue protein clearance. Target-to
      background tissue (T/Bkg) ratios were calculated for each radioprotein and
      compared with the T/Bkg ratio for (111)In-leukocytes. (99m)Tc-Sulesomab binding
      to granulocytes was measured in vitro and ex vivo and to primed and activated
      granulocytes in vitro. RESULTS: After intravenous injection, <5% of the
      circulating radioactivity was cell bound with both radioproteins so that the P-R
      curves could therefore be assumed to represent extravascular uptake of free
      protein. The blood clearance (mean +/- SD) of sulesomab was 23.4 +/- 11.7 mL/min,
      approximately 5 times greater than that of HSA, for which it was 4.8 +/- 3.1
      mL/min. Likewise, clearance into the lesion of sulesomab was consistently higher
      than that of HSA, on average about 3 times as high. Nevertheless, the T/Bkg
      ratios for sulesomab and HSA were similar, except at 6 h when that of HSA (2.14
      +/- 0.6) was higher than that of sulesomab (1.93 +/- 0.5; P approximately 0.01).
      Both values were considerably less than the T/Bkg ratio on the (111)In-leukocyte
      images, which, at 22 h, was 12.3 +/- 5.3. Moderate clearance of sulesomab, but
      not HSA, was seen in the control tissue. Granulocytes bound significantly more
      (99m)Tc-sulesomab in vitro when primed or activated. CONCLUSION: (a) Sulesomab
      does not localize in inflammation as a result of binding to circulating
      granulocytes; (b) sulesomab is cleared into inflammation nonspecifically via
      increased vascular permeability; nevertheless, it may be cleared after local
      binding to primed granulocytes or bind to activated, migrated extravascular
      granulocytes; and (c) HSA produces a similar or higher T/Bkg ratio than sulesomab
      because sulesomab is cleared into normal tissues and because image positivity in
      inflammation is significantly dependent on local blood-pool expansion.

PMID- 12515871
TI  - Dipyridamole, cold pressor test, and demonstration of endothelial dysfunction: a
      PET study of myocardial perfusion in diabetes.
AB  - Much evidence suggests endothelial dysfunction to be present in non-insulin
      dependent diabetes mellitus (NIDDM) and to be important for the development of
      myocardial ischemia. Endothelial function in the coronary vessels may be studied
      in various ways. We compared the effect of cold pressor testing (CPT) with that
      of dipyridamole, a pharmacologic vasodilator, on coronary blood flow (CBF)
      measured by PET in NIDDM patients and healthy volunteers. In addition, we studied
      the effect of acute angiotensin-converting enzyme (ACE) inhibition on the flow
      response. METHODS: Ten NIDDM patients and 10 control subjects participated.
      Myocardial perfusion was determined at baseline, during CPT, and after
      dipyridamole infusion by PET using intravenous (13)N-ammonia. RESULTS: Resting
      CBF was similar in NIDDM patients and in control subjects. CPT increased CBF by
      20% in the control group, whereas no increase was observed in the patients. After
      dipyridamole infusion, CBF increased 2- to 3-fold in patients and 3- to 4-fold in
      control subjects. The increase and maximal CBF were significantly higher in
      control subjects than in patients. During ACE-inhibitor infusion, which had no
      influence on resting CBF in patients or control subjects (n = 5), CPT increased
      CBF by 14% in the NIDDM group. After dipyridamole, CBF increased 3- to 4-fold in
      both groups. The increase in CBF and maximal CBF in the 2 groups were not
      different during ACE-inhibitor infusion. CONCLUSION: In these NIDDM patients
      without evidence of epicardial coronary disease, endothelial dysfunction is
      strongly suggested by an impaired increase in CBF both to dipyridamole and to
      CPT. This dysfunction was reversed by infusion of an ACE inhibitor. Although ACE
      inhibition during CPT did induce significant increases in CBF in the patients,
      the changes during ACE inhibition were small compared with the dipyridamole
      response, and the absence of CBF increase during CPT in 3 of the 10 control
      subjects further limits the value of CPT for the study of coronary endothelial
      dysfunction.

PMID- 12515872
TI  - Impact of whole-body 18F-FDG PET on staging and managing patients for radiation
      therapy.
AB  - Whole-body PET with (18)F-FDG has proven to be a very effective imaging modality
      for staging of malignant tumors. This study was performed to evaluate the impact
      of (18)F-FDG PET on staging and managing patients for radiation therapy. METHODS:
      The treatment records of 202 consecutive patients (98 male, 104 female; mean age,
      56.9 y; age range, 8-91 y) with different malignant tumors were reviewed.
      Radiation therapy was intended for all patients. The diagnoses were head and neck
      tumors (n = 55), gynecologic tumors (n = 28), breast cancer (n = 28), lung cancer
      (n = 26), malignant lymphomas (n = 24), tumors of the gastrointestinal tract (n =
      18), and others (n = 23). Whole-body PET was performed before radiation therapy.
      The alteration of PET on each patient's staging and management decisions for
      radiation therapy were determined. RESULTS: For 55 of 202 patients (27%), PET
      results changed the patients' management in radiation therapy. In 18 cases (9%),
      PET resulted in a cancellation of radiation therapy because of the detection of
      previously unknown distant metastases (8 patients), additional lymph node
      metastases (9 patients), residual tumor (6 patients), or the exclusion of active
      disease (2 patients). In 6 patients, >1 incremental reason was found for
      cancellation. In 21 PET examinations (10%), PET results changed the intention of
      radiation treatment (curative or palliative). The radiation dose was changed in
      25 cases (12%). A change of radiation volume was necessary in 12 patients (6%).
      CONCLUSION: The results of this study show that (18)F-FDG PET has a major impact
      on the management of patients for radiation therapy, influencing both the stage
      and the management in 27% of patients.

PMID- 12515873
TI  - 18F-FDG PET in candidates for radiation therapy: is it important and how do we
      validate its impact?

PMID- 12515874
TI  - Comparison of microsphere-equivalent blood flow (15O-water PET) and relative
      perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion
      mismatch.
AB  - Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption
      of a linear correlation between myocardial blood flow (MBF) and tracer uptake.
      However, it is known that (99m)Tc-tetrofosmin uptake is directly related to
      energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as
      well as cellular and mitochondrial membrane potentials. Therefore, cellular
      alterations that affect these energy-dependent transport processes ought to
      influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because
      metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM)
      reflects impaired but viable myocardium showing cellular alterations, MPMM was
      chosen to quantify the blood flow-independent effect of cellular alterations on
      (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF
      (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in
      "normal" myocardium. METHODS: Forty-two patients with severe coronary artery
      disease, referred for myocardial viability diagnostics, were examined using (18)F
      FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc
      tetrofosmin uptake values were calculated using 18 segments per patient. Normal
      myocardium and MPMM myocardium were classified using a previously validated
      (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was
      performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue
      fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable
      to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were
      calculated for all normal and MPMM segments and averaged within their respective
      classifications. RESULTS: Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1%
      in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P
      < 0.001), as was expected from the classification. Contrary to these findings,
      mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which
      did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x
      mL(-1)). All values are given as mean +/- SEM. CONCLUSION: Differences between
      reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium
      suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but
      cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin
      independently of blood flow. Therefore, it seems that perfusion deficits in MPMM
      myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to
      give false-positive findings.

PMID- 12515875
TI  - Quantification in SPECT cardiac imaging.

PMID- 12515876
TI  - The third circulation: radionuclide lymphoscintigraphy in the evaluation of
      lymphedema.
AB  - Lymphedema-edema that results from chronic lymphatic insufficiency-is a chronic
      debilitating disease that is frequently misdiagnosed, treated too late, or not
      treated at all. There are, however, effective therapies for lymphedema that can
      be implemented, particularly after the disorder is properly diagnosed and
      characterized with lymphoscintigraphy. On the basis of the lymphoscintigraphic
      image pattern, it is often possible to determine whether the limb swelling is due
      to lymphedema and, if so, whether compression garments, massage, or surgery is
      indicated. Effective use of lymphoscintigraphy to plan therapy requires an
      understanding of the pathophysiology of lymphedema and the influence of technical
      factors such as selection of the radiopharmaceutical, imaging times after
      injection, and patient activity after injection on the images. In addition to
      reviewing the anatomy and physiology of the lymphatic system, we review
      physiologic principles of lymphatic imaging with lymphoscintigraphy, discuss
      different qualitative and quantitative lymphoscintigraphic techniques and their
      clinical applications, and present clinical cases depicting typical
      lymphoscintigraphic findings.

PMID- 12515877
TI  - Performance evaluation of a modular gamma camera using a detectability index.
AB  - The performance of a modular gamma camera for the task of detecting signals in
      random noisy backgrounds was evaluated experimentally. The results were compared
      with a theoretical computer simulation. METHODS: The camera uses a 10 x 10 cm
      thallium-doped sodium iodide crystal, a 2 x 2 array of 53 x 53 mm photomultiplier
      tubes, and a parallel-hole collimator (1.5-mm bore width, 23.6-mm bore length).
      The camera was positioned to look down into a 10-cm-deep water bath that filled
      its field of view (FOV). The top surface of the water was 5 cm from the front
      face of the camera. The camera has 3-mm intrinsic spatial resolution (SR) in the
      center of its FOV and 9-mm system SR for objects 5 cm below the top surface of
      the water. Uniform and nonuniform random background data were collected by
      imaging the bath containing 740 MBq (20 mCi) (99m)Tc. Nonuniformities were
      created by placing water-filled objects in the bath. Each signal dataset was
      collected by imaging a water-filled plastic sphere, injected with (99m)Tc and set
      at a specific depth (Z) in the bath. Data were collected for many signal
      diameters (D) (4, 7, 10, 13, 16, 28 mm) at 1 depth (5 cm) and for 1 signal
      diameter (10 mm) at several depths (1, 3, 5, 7, 9 cm). Sets of signal
      present/signal-absent image pairs (380 pairs, 10(5) events per image) for known
      contrasts (C) were generated for use in ideal-observer studies in which the
      detectability (d') was calculated. Contrast-detail (log C vs. log D) plots were
      created. The theoretical simulation, developed for uniform backgrounds, provided
      data for comparison. RESULTS: The detectability increased linearly with C and
      decreased nonlinearly with decreasing D or increasing Z. The C required to
      achieve a specific d' increased sharply for D < SR. For C = 5, D = 10 mm, and d'
      = 1.2, the camera consistently detected signals for Z < 6 cm. Similar results
      were found for nonuniform backgrounds. The theoretical simulation verified the
      results for uniform backgrounds. CONCLUSION: The methodology presented here
      provides a way of evaluating gamma cameras on the basis of signal-detection
      performance for specified lesions, with particular application to
      scintimammography.

PMID- 12515878
TI  - Red marrow radiation dose adjustment using plasma FLT3-L cytokine levels:
      improved correlations between hematologic toxicity and bone marrow dose for
      radioimmunotherapy patients.
AB  - Calculated red marrow absorbed dose in patients receiving radioimmunotherapy
      (RAIT) has not been highly predictive of the dose-limiting hematologic toxicity
      observed in many patient populations studied. Because patients receiving the same
      red marrow dose often experience different grades of toxicity, other factors
      might help predict the different grades of toxicity observed. One such factor may
      be the plasma FLT3-L (FMS-related tyrosine kinase 3 ligand, hematopoiesis
      stimulatory cytokine) level, which has been shown to be a better indicator of
      recovery of progenitor cells and, thus, red marrow radiosensitivity (because
      during the recovery period the progenitor cells are hyperproliferative and
      potentially more radiosensitive) for patients treated with previous chemotherapy
      than peripheral blood counts. METHODS: Red marrow radiation doses were determined
      for 30 patients (20 male, 10 female; all without bone marrow or bone involvement;
      19 had prior chemotherapy) after receiving (131)I RAIT (activity range, 2.1-8.9
      GBq) for treatment of solid cancers known to produce carcinoembryonic antigen.
      Radiation dose estimates were calculated using 2 different methods of red marrow
      cumulated activity and red marrow-to-blood activity concentration ratio
      determinations for 2 dosimetric models: using both male and female and male-only
      masses and S values. Highest platelet toxicity grade at nadir (PTG), percentage
      platelet decrease (PPD) in counts, and platelet nadir (PN) counts were measured.
      FLT3-L levels (pg/mL) were determined by immunoassay before treatment; a normal
      FLT3-L level was assumed to be 80 pg/mL. The red marrow radiation doses (cGy)
      were adjusted for the patient's FLT3-L level when the patient's cytokine level
      exceeded the normal value. Marrow doses and FLT3-L-adjusted marrow doses were
      correlated with PTG, PPD, PN, and 1/PN. Administered activity, administered
      activity per unit body weight, and total body radiation dose were also correlated
      with these hematologic toxicity measures. RESULTS: All red marrow dose
      calculation schemes resulted in essentially the same correlations for a given
      hematologic toxicity measure. Poor correlations were observed between
      administered activity, administered activity per unit body weight, total body
      radiation dose, or red marrow radiation dose and PTG, PPD, PN, and 1/PN. All
      correlations improved greatly when the various predictors of toxicity were
      adjusted for the patient's FLT3-L level. The highest correlation observed was
      between red marrow dose or total body dose and 1/PN (r = 0.86). Using an
      unadjusted red marrow dose to predict toxicity >/= grade 3, there were 8 true
      positive, but 13 false-positive cases with 9 true-negatives. However, using a
      FLT3-L-adjusted red marrow dose, there were 8 true-positives, but only 2 false
      positives and 20 true-negatives. CONCLUSION: FLT3-L-adjusted red marrow radiation
      doses provide improved correlation with hematologic toxicity. Thus, elevated FLT3
      L plasma levels before RAIT may indicate increased radiosensitivity of the bone
      marrow, and use of this measurement to adjust calculated red marrow or total body
      radiation doses may provide significantly better prediction of toxicity than
      radiation dose alone, leading to a patient-specific administered activity
      prescription that will deliver radiation doses to diseased tissues sufficient to
      produce an effective treatment outcome at acceptable toxicity levels.

PMID- 12515879
TI  - 90Y-DOTA-hLL2: an agent for radioimmunotherapy of non-Hodgkin's lymphoma.
AB  - The goal of this work was to determine an optimal radioimmunotherapy agent for
      further development against non-Hodgkin's lymphoma. We sought to establish the
      stability profile of (90)Y-labeled humanized LL2 (hLL2) monoclonal antibody (mAb)
      when prepared with different chelating agents and, from these data, to estimate
      the dosimetric improvement to be expected from use of the most stable (90)Y
      chelate-hLL2 complex. METHODS: The complementarity-determining region-grafted
      (humanized) anti-CD22 mAb, hLL2 (epratuzumab), was conjugated to 3 different
      chelating agents, 2 of which were derivatives of diethylenetriaminepentaacetic
      acid (DTPA) and 1 of which was the macrocyclic chelate 1,4,7,10
      tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA). The 3 hLL2 conjugates
      were radiolabeled with (90)Y and tested for stability in vitro against a 10,000
      fold molar excess of free DTPA over 9 d. They were also tested against normal
      human serum at 37 degrees C over 12 d. Each conjugate was radiolabeled with the
      gamma-emitting radionuclide, (88)Y, and compared for biodistribution in normal
      and lymphoma xenograft-bearing athymic mice. In vivo data were analyzed for
      statistical differences in the uptake of yttrium in bone and washed bone when
      either the DOTA or the Mx-DTPA chelates were used, and dosimetry calculations
      were made for each complex. RESULTS: (90)Y-DOTA complex of the hLL2 mAb was
      completely stable to either DTPA or serum challenge for the duration of either
      experiment (equivalent to 3.3-4.5 half-lives of (90)Y radionuclide or >90% of
      possible (90)Y decays from any initial starting activity). Complexes of hLL2 that
      had been prepared using the DTPA-type chelates lost 3%-4% of initially bound
      (90)Y over the first few days and about 10%-15% over the duration of the
      challenges. In vivo, these stability differences manifested as significantly
      lower yttrium uptake in bone and cortical bone over a 10-d period when DOTA was
      used as the yttrium chelating agent. Absorbed doses per 37 MBq (1 mCi) of (90)Y
      mAb were 3,555 and 5,405 cGy for bone and 2,664 and 4,524 cGy for washed bone for
      (90)Y-DOTA-hLL2 and (90)Y-MxDTPA-hLL2, respectively, amounting to 52.0% and 69.8%
      increases in absorbed radiation doses for bone and washed bone, respectively,
      when a DOTA chelate was switched to a Mx-DTPA chelate. CONCLUSION: (90)Y-hLL2
      prepared with the DOTA chelate represents an improved agent for
      radioimmunotherapy of non-Hodgkin's lymphoma, with an in vivo model demonstrating
      a large reduction in bone-deposited yttrium, compared with (90)Y-hLL2 agents
      prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this
      benefit will result in a substantial toxicologic advantage for a DOTA-based hLL2
      conjugate.

PMID- 12515880
TI  - Repetitive supply-demand ischemia with dobutamine increases glucose uptake in
      postischemic and remote myocardium.
AB  - The goal of this study was to determine whether myocardial glucose uptake after
      repetitive ischemia differs in response to coronary occlusion-reperfusion versus
      supply-demand ischemia induced by dobutamine. Although glucose metabolism is
      increased after myocardial ischemia, the metabolic effect of supply-demand
      ischemia induced by dobutamine may increase glucose metabolism within remote
      myocardium. This would make it difficult to discriminate postischemic from remote
      myocardium with glucose tracers. METHODS: Eighteen swine with a hydraulic
      occluder and flow probe on the circumflex artery underwent repetitive ischemia.
      In group 1 (n = 9), the circumflex artery was occluded, whereas in group 2 (n =
      9), circumflex flow was decreased by 30% before dobutamine (40 micro g/kg/min
      intravenously). Each pig underwent 15 min of ischemia, twice per day for 5 d.
      Echocardiography and PET to determine myocardial glucose ((18)F-FDG) uptake were
      performed after final ischemia, and tissue was later analyzed for activation of
      Akt, p38 mitogen-activated protein, and adenosine monophosphate (AMP) kinase.
      RESULTS: Wall thickening in the circumflex region was lower than in remote
      regions in both groups. (18)F-FDG uptake in the circumflex region was similar in
      groups 1 and 2 (0.22 +/- 0.03 and 0.23 +/- 0.04 micro mol/min/g, respectively;
      not statistically significant). In the remote region, (18)F-FDG uptake was lower
      than in the circumflex region in group 1 (0.14 +/- 0.03 micro mol/min/g; P <
      0.05) but was similar to that in the circumflex region in group 2 (0.20 +/- 0.03
      micro mol/min/g; not statistically significant). AMP kinase activity in the
      remote region was significantly lower than in the circumflex region in group 1
      but was similar to that in the circumflex region in group 2. CONCLUSION: Unlike
      repetitive coronary artery occlusion-reperfusion, repetitive supply-demand
      ischemia with dobutamine alters glucose uptake within the remote myocardium,
      possibly as a result of AMP kinase activation. Clinically, these data suggest
      that (18)F-FDG studies have a limited role in discriminating postischemic from
      remote myocardium after dobutamine stress.

PMID- 12515881
TI  - Detection of apoptotic tumor response in vivo after a single dose of chemotherapy
      with 99mTc-annexin V.
AB  - Annexin V, a human protein with a high affinity for phosphatidylserine, has been
      labeled with (99m)Tc to detect apoptosis in vivo. To determine the effectiveness
      of imaging with this agent as a reflection of the degree of apoptosis after the
      first dose of chemotherapy, we studied rats with an engrafted hepatoma. METHODS:
      Annexin V was labeled with (99m)Tc (specific activity, 3.0 MBq/ micro g protein).
      Eleven days after being inoculated with allogenic hepatoma cells (KDH-8) in the
      left calf muscle, the rats were randomized to receive a single dose of
      cyclophosphamide (150 mg/kg intraperitoneally) or to serve as controls. (99m)Tc
      annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h
      after injection of (99m)Tc-annexin V. Tumor uptake of (14)C-iodoanitpyrine was
      determined as a marker of tumor blood flow. Terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick-end labeling (TUNEL) of tissue harvested
      at necropsy was performed to detect apoptosis in the tumor. RESULTS:
      Cyclophosphamide treatment significantly increased the tumor uptake (percentage
      activity of injected dose per gram of tissue after normalization to the animal's
      weight [%ID/g/kg]) of (99m)Tc-annexin V (0.070 +/- 0.007 %ID/g/kg for treated
      rats and 0.046 +/- 0.009 %ID/g/kg for controls, P < 0.001). (14)C-iodoantipyrine
      uptake was similar in the treated and untreated groups. The number of TUNEL
      positive cells in the tumor was significantly larger in the treated rats (297.70
      +/- 50.34 cells/mm(2)) than in the control rats (168.45 +/- 23.60 cells/mm(2), P
      < 0.001). Tumor uptake of (99m)Tc-annexin V correlated with the number of TUNEL
      positive cells in the tumor (r = 0.712; P < 0.001). CONCLUSION: Tumor uptake of
      (99m)Tc-annexin V was significantly increased by a single dose of
      cyclophosphamide treatment, and the increase was concordant with the number of
      TUNEL-positive cells in the tumor. The current results are suggestive of the
      utility of (99m)Tc-annexin V as a noninvasive means to assess tumor response,
      although further testing, including clinical evaluation, is required.

PMID- 12515882
TI  - Peptide receptor radionuclide therapy in vitro using [111In-DTPA0]octreotide.
AB  - Peptide receptor radionuclide therapy (PRRT) using [(111)In-DTPA(0)]octreotide
      (where DTPA is diethylenetriaminepentaacetic acid) is feasible because, besides
      gamma-radiation, (111)In emits both therapeutic Auger and internal conversion
      electrons having a tissue penetration of 0.02-10 and 200-500 micro m,
      respectively. The aim of this study was to investigate the therapeutic effects of
      [(111)In-DTPA(0)]octreotide in a single-cell model including the effects of
      incubation time, radiation dose, and specific activity of [(111)In
      DTPA(0)]octreotide. Finally, we discriminated between the effects of the Auger
      electrons and internal conversion electrons in PRRT. METHODS: An in vitro, colony
      forming assay to study cell survival after PRRT using the sst subtype 2-positive
      rat pancreatic tumor cell line CA20948 was developed. RESULTS: In this in vitro
      system [(111)In-DTPA(0)]octreotide can control tumor growth to 0% survival, and
      the effects were dependent on incubation time, radiation dose, and specific
      activity used. Similar concentrations of (111)In-DTPA, which is not internalized
      into sst-positive tumor cells like [(111)In-DTPA(0)]octreotide, did not influence
      tumor survival. Excess unlabeled octreotide (10(-6) mol/L) could decrease tumor
      cell survival to 60% of control; the addition of radiolabeled peptide ([(111)In
      DTPA(0)]octreotide [10(-9) mol/L] + 10(-6) mol/L octreotide) did not further
      decrease survival. CONCLUSION: These in vitro studies show that the therapeutic
      effect of (111)In is dependent on internalization, enabling the Auger electrons
      with their very short particle range to reach the nucleus. Our results also
      indicate that the PRRT effects were receptor mediated.

PMID- 12515883
TI  - Measurement of brain concentration of FK960 for development of a novel
      antidementia drug: a PET study in conscious rhesus monkeys.
AB  - This study used PET to measure the time course of the brain concentration of
      (18)F-labeled N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a
      novel antidementia drug, after oral administration to conscious rhesus monkeys.
      METHODS: Three young-adult male rhesus monkeys were tested. FK960 (0.1 mg/kg)
      containing about 370 MBq of (18)F-FK960 was administered orally to each monkey.
      Dynamic PET images were acquired for 4 h from 5 min after the administration.
      Arterial blood samples were withdrawn during PET scanning and were analyzed by an
      automatic well gamma-counter and thin-layer chromatography to determine the time
      course of authentic (18)F-FK960 activity concentration in plasma. FK960
      concentrations in brain and plasma were calculated in units of mol/L using the
      specific activity of FK960 preparations. RESULTS: (18)F-FK960 penetrated the
      blood-brain barrier and underwent perfusion-dependent distribution in the entire
      brain. Maximal concentrations in the brain and plasma were 1.11 +/- 0.30 x 10(-7)
      mol/L (at 3.0 +/- 0.6 h after administration) and 4.04 +/- 1.29 x 10(-7) mol/L
      (at 2.0 +/- 1.1 h after administration), respectively. CONCLUSION: We succeeded
      in measuring the FK960 concentration in the brains of conscious monkeys and in
      plasma after oral administration at a dose of 0.1 mg/kg. The results suggested
      that this method can measure the FK960 concentration in the human brain, and a
      potential use of the PET technique in drug development was demonstrated.

PMID- 12515884
TI  - Quantification of D2-like dopamine receptors in the human brain with 18F
      desmethoxyfallypride.
AB  - Substituted benzamides such as (11)C-raclopride or (123)I-iodobenzamide are
      selective radiotracers for PET and SPECT imaging of D(2)-like dopamine (DA)
      receptors. (18)F-Desmethoxyfallypride ((18)F-DMFP) is a benzamide tracer with the
      advantage of an (18)F label. We optimized the synthesis and evaluated (18)F-DMFP
      in PET studies on healthy human volunteers. METHODS: The affinity of DMFP for
      D(2)-like DA receptors was characterized in vitro using membrane preparations
      from rat striatum and the DA receptor ligand (3)H-spiperone. PET studies on 10
      healthy human volunteers were performed using a whole-body PET scanner after
      injection of 214 +/- 54 MBq (mean +/- SD) (18)F-DMFP. Brain images were acquired
      dynamically over 124 min, and metabolite-corrected plasma activity was used as
      the input function. Data analysis was performed using several different
      approaches (compartmental, graphical, equilibrium methods). RESULTS: The mean
      inhibition constant (K(i)) of DMFP was 15 +/- 9 nmol/L. In human brain, the
      striatum-to-cerebellum ratio reached a maximum of about 4 between 60 and 120 min.
      When specific binding in the striatum was expressed as the difference between
      binding in the striatum and the cerebellum, it reached a maximum at approximately
      60 min after injection and remained almost constant until the end of data
      acquisition. The ratio of specific striatal to nonspecific cerebellar binding was
      about 3:1 at 120 min after injection. A small, but significant specific tracer
      binding could also be detected in the thalamus. Treatment of a schizophrenic
      patient with a high dose (1,000 mg/d) of another substituted benzamide,
      amisulpride, resulted in a reduction of specific tracer uptake of about 90% in
      striatal regions. With regard to measured distribution volumes and binding
      potentials, there was an excellent agreement between all applied analytic
      methods. CONCLUSION: Our study demonstrates that (18)F-DMFP is a highly reliable
      tracer for PET imaging of D(2)-like DA receptors. It offers the major advantage
      that it can be used independently of an on-site cyclotron within a PET satellite
      network. Noninvasive analytic methods without blood sampling provide valid
      measurements of receptor quantities in human striatum. Because of the (18)F label
      and the favorable imaging properties, (18)F-DMFP could become an efficient
      substitute for (11)C-raclopride in a clinical context.

PMID- 12515885
TI  - Increased sensitivity in detection of a porcine high-turnover osteopenia after
      total gastrectomy by dynamic 18F-fluoride ion PET and quantitative CT.
AB  - High-resolution (18)F-fluoride ion PET in combination with quantitative CT (QCT)
      allows the assessment of bone metabolism in relation to bone mass. This combined
      imaging approach was used to elucidate porcine bone metabolic changes after
      gastrectomy, which are frequently associated with osteopenia or osteomalacia.
      METHODS: Six months after total gastrectomy (n = 7) or sham operation (n = 6),
      bone blood flow and bone metabolic activity (K(i), K(flux)) were calculated from
      dynamic PET measurements from vertebral bodies and compared with corresponding
      QCT bone mineral density (BMD) measurements. RESULTS: Total gastrectomy resulted
      in a significant reduction of the BMD (-21%; P < 0.005), whereas 1,25-(OH)(2)
      vitamin D, serum phosphate, and parathyroid hormone were significantly increased
      compared with that of sham-operated animals. Because of the significant increase
      of the rate constant k(3) (+325%; P < 0.05), describing chemisorption and
      incorporation of (18)F-fluoride onto or into the bone matrix, K(i) (+36%) and
      K(flux) (+37%) were significantly elevated after total gastrectomy compared with
      that of control animals (P < 0.01), whereas bone blood flow was not significantly
      different between groups. The normalization of K(i) and K(flux) values by the
      specific bone mass (K(i/BMD); K(flux/BMD)) largely increased the differences
      between groups (K(i/BMD), +74%; K(flux), +76%; P < 0.001). CONCLUSION: Dynamic
      (18)F-fluoride ion PET revealed that porcine bone loss after total gastrectomy is
      related to a high-turnover bone disease without significant changes in bone blood
      flow. In mini pigs, the increased bone metabolism is probably related to an
      elevated parathyroid hormone secretion, thus maintaining serum calcium
      homeostasis at the expense of the bone mineral content. Normalizing bone
      metabolic activity by the specific bone mass increases the sensitivity in the
      detection of osteopenic high-turnover bone diseases. Therefore, the combination
      of QCT and (18)F-fluoride ion PET seems to be the method of choice for the
      classification of metabolic bone diseases and for monitoring treatment effects
      quantitatively.

PMID- 12515886
TI  - Biologic responses to low doses of ionizing radiation: adaptive response versus
      bystander effect.

PMID- 12515887
TI  - Plasticity of gamma-aminobutyrate receptors in the medial vestibular nucleus of
      rat after inferior cerebellar peduncle transection.
AB  - Extracellular single unit recordings were made from regularly discharging medial
      vestibular nucleus neurons in brain slices from control rats and from rats
      surviving 7 days after bilateral transection of the inferior cerebellar peduncle.
      Decreases in firing rate during perfusion with the gamma-aminobutyric acid (GABA)
      agonists, muscimol (GABA(A)) and baclofen (GABA(B)), were greater in lesioned
      rats than in control rats. For the grouped data, the half-maximally-effective
      concentrations of muscimol and baclofen were 3.2 microM, as compared with 19.6
      microM for control, and 0.8 microM, as compared with 2.7 microM for control,
      respectively. The antagonists bicuculline (GABA(A)) and 2-OH-saclofen (GABA(B))
      only minimally affected the spontaneous firing rates of neurons in lesioned rats,
      significantly less than in control rats. The data suggest that the decreases of
      endogenous GABA levels in the medial vestibular nucleus after inferior cerebellar
      peduncle transection are accompanied by up-regulation of GABA(A) and, to a lesser
      extent, GABA(B) receptors.

PMID- 12515888
TI  - Spatial orientation of postrotatory nystagmus during static roll tilt in cats.
AB  - While the stimulation of otolith inputs reduces the duration of postrotatory
      nystagmus (PRN), there is still room for dialogue about the effect of static tilt
      on the orientation of PRN. We studied one possible influence of static roll tilt
      on the spatial orientation of PRN in cats. The animal was rotated about an earth
      vertical axis (EVA) at a constant velocity of 100 deg/s with an acceleration and
      deceleration of 120 deg/s2. Within two seconds after stopping EVA rotation, the
      animal was passively tilted at 45 deg/s about its longitudinal axis by as much as
      +/- 90 deg in steps of 15 deg. Eye movements were measured with magnetic search
      coils. The angle of the PRN plane and its slow phase eye velocity were measured.
      The time constant of PRN decreased with an increase in roll tilt. The PRN plane
      remained earth horizontal within a range of +/- 30 deg roll tilt. Beyond this
      range, the velocity of PRN decreased too rapidly to measure any change in
      orientation. Our results indicate a spatially limited and temporally short
      interaction of the semicircular canal and otolith signals in the velocity storage
      mechanism of cat PRN. Our data, along with previous studies, suggest that
      different species show different solutions to the problem of the imbalance and
      spatial disorientation during contradictory stimuli.

PMID- 12515889
TI  - Modeling head tracking of visual targets.
AB  - Control of the head involves somatosensory, vestibular, and visual feedback. The
      dynamics of these three feedback systems must be identified in order to gain a
      greater understanding of the head control system. We have completed one step in
      the development of a head control model by identifying the dynamics of the visual
      feedback system. A mathematical model of human head tracking of visual targets in
      the horizontal plane was fit to experimental data from seven subjects performing
      a visual head tracking task. The model incorporates components based on the
      underlying physiology of the head control system. Using optimization methods, we
      were able to identify neural processing delay, visual control gain, and neck
      viscosity parameters in each experimental subject.

PMID- 12515890
TI  - Vestibular evoked myogenic potentials in response to laterally directed skull
      taps.
AB  - In recent years it has been demonstrated that loud clicks generate short latency
      vestibular evoked myogenic potentials (VEMP). It has also been demonstrated that
      midline forehead skull tap stimulation evokes similar VEMP. In the present study,
      the influence of skull tap direction on VEMP was studied in 13 normal subjects
      and in five patients with unilateral vestibular loss. Gentle skull taps were
      delivered manually above each ear on the side of the skull. The muscular
      responses were recorded over both sternocleidomastoid muscles using skin
      electrodes. Among the normals, laterally directed skull taps evoked "coordinated
      contraction-relaxation responses", i.e. skull taps on one side evoked a negative
      positive "inverted" VEMP on that side and a positive-negative "normal" VEMP on
      the other side. Among patients with unilateral vestibular function loss, skull
      taps above the lesioned ear evoked similar coordinated contraction-relaxation
      responses. However, skull taps above the healthy ear did not evoke that type of
      response. These findings suggest that laterally directed skull taps activate
      mainly the contralateral labyrinth.

PMID- 12515891
TI  - Improvements in path integration after vestibular rehabilitation.
AB  - Fifty-three subjects with peripheral, chronic vestibulopathies, who were referred
      for vestibular rehabilitation, were tested on a path integration task before and
      after doing four weeks of five times daily habituation exercises for vertigo
      reduction. The task involved walking over a 7.62 m path with eyes closed.
      Dependent measures were velocity and angle of veering from the straight ahead. At
      the post-test and at succeeding follow-up tests for up to six months, subjects
      had significant increases in velocity and significant declines in angle of
      veering. Length of time subjects had vertigo prior to starting rehabilitation,
      and speed of head movement exercises were not associated with improvements. These
      data support the previous finding that patients with vestibular impairments have
      decreased performance on this task. The data also suggest that vestibular
      rehabilitation, given as a simple home program, is associated with improvements
      in this skill.

PMID- 12515892
TI  - Effects of lifetime ethanol consumption on postural control: a computerized
      dynamic posturography study.
AB  - The relationship between lifetime alcohol consumption and postural control was
      investigated in 35 subjects with no clinically-detectable neurologic
      abnormalities, using computerized dynamic posturography (CDP) procedures. The
      estimated total number of lifetime alcoholic drinks was positively correlated
      with anteroposterior sway spectral power within the 2-4 Hz and 4-6 Hz frequency
      bands, in three Sensory Organization Test (SOT) conditions: eyes closed with
      stable support surface (SOT 2), eyes open with sway-referenced support (SOT 4),
      and eyes closed with sway-referenced support (SOT 5). All correlations remained
      significant after controlling for subject age, and were increased after excluding
      nine drug-abusing subjects. In contrast to the strong findings for frequency
      based measures, no correlation was observed using conventional amplitude-based
      sway measures. These results suggest that 1) alcohol consumption compromises
      postural control in an exposure-dependent manner, and 2) sway frequency analysis
      reveals pathological processes not manifested in conventional CDP measures of
      sway amplitude.

PMID- 12515893
TI  - Alignment of collagen and laminin-containing gels improve nerve regeneration
      within silicone tubes.
AB  - PURPOSE: Placement of extracellular matrix components has been used as a mean to
      enhance axonal growth across nerve long gaps repaired by tubulization. However,
      such matrices may impede axonal regeneration depending on its density and
      microgeometry. METHODS: Silicone tubes were prefilled with collagen or laminin
      containing gels and implanted into a 6 mm gap, a length considered limiting for
      regeneration, in the mouse sciatic nerve. Gels were polymerized prior to
      implantation either in horizontal position or subjected to gravitational (in
      vertical position) or to magnetic forces to induce longitudinal alignment of the
      fibrils. Recovery of motor, sensory and sudomotor functions in the hindpaw was
      evaluated during 4 months postoperation. RESULTS: Reinnervation started earlier
      and achieved slightly higher levels with aligned collagen gels than with the
      horizontal gel. For the three groups repaired with tubes with Matrigel, there was
      a gradation of the functional results, reinnervation started earlier and reached
      higher values in matrix with magnetically-induced, longitudinal orientation than
      with the horizontal gel, whereas gravitational alignment followed an intermediate
      evolution. Final morphological evaluation showed more dense residual mass of
      collagen than of Matrigel at the center of the regenerate nerves. The number of
      myelinated fibers was increased in tubes with alignment compared to horizontal
      gels. CONCLUSIONS: Alignment of collagen and laminin gels within a silicone tube
      increases the success and the quality of regeneration in long nerve gaps. The
      laminin gel performed better than the collagen gel under each condition tested.
      The combination of an aligned matrix with embedded Schwann cells should be
      considered in further steps for the development of an artificial nerve graft for
      clinical application.

PMID- 12515894
TI  - Experimental hyperthyroidism increases the effectiveness of predegenerated
      peripheral nerve graft implantation into hippocampus of adult rats.
AB  - PURPOSE: The aim of the study was to ascertain whether experimental
      hyperthyroidism changes the neurotrophic activity of 14- and 21-day
      predegenerated peripheral nerve grafts towards CNS neurites. METHODS:
      Hyperthyroidism was induced by subcutaneous injections of T_4. Autologous
      peripheral nerve grafts were implanted into the hippocampus of both euthyrotic
      and hyperthyrotic animals 14 or 21 days after sciatic nerve transection (groups
      ET14, Et21, Ht14 and Ht21, respectively). Non-predegenerated grafts were used as
      a control group (groups EtN adn HtN). Cells extending their neurites into the
      grafts were traced with FITC-HRP. RESULTS: The number of traced cells in
      individual groups was as follows: EtN - 39.4 +/- 9.46, Et14 - 1 +/- 0.94, Et21 -
      0.6 +/- 0.69; HtN - 95 +/- 19.46; Ht14 - 95.94 +/- 16.3, Ht21 - 99.94 +/- 7.26.
      CONCLUSIONS: We found that experimentally induced hyperthyroidism strongly
      enhanced the regeneration of injured hippocampal neurites after implantation of
      peripheral nerve grafts that were practically inactive in euthyrotic animals.

PMID- 12515895
TI  - Descending systems contributing to locomotor recovery after mild or moderate
      spinal cord injury in rats: experimental evidence and a review of literature.
AB  - PURPOSE: Locomotor recovery after spinal cord contusion injury (SCI) may be
      mediated by descending axons spared at the lesion epicenter. Greater axonal
      sparing is associated with more extensive recovery. Therefore, we identified the
      source and relative proportion of spared axons associated with extensive or
      limited locomotor recovery after SCI. METHODS: Female Sprague Dawley rats
      underwent mild or moderate SCI using the OSU device. RESULTS: Locomotor recovery
      was greater for the mild than moderate group with the primary differences being
      restitution of limb coordination, very little toe dragging and minor paw
      rotation. CONCLUSIONS: The following brain nuclei with substantial neuronal
      labeling after mild but not moderate SCI may play an important role in locomotor
      recovery: raphe pallidus and magnus, ventral medullary and pontine reticular
      formation, lateral vestibular nucleus, red nucleus and locus coeruleus. We review
      the normal anatomical distribution of descending systems to the lumbar cord in
      rat and the role they play in motor control.

PMID- 12515896
TI  - 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering
      cerebral amyloid-beta levels in AbetaPPSWE transgenic mice.
AB  - Post-menopausal estrogen therapy is associated with a decreased incidence of
      Alzheimer disease and in vitro models have shown that 17beta-estradiol is
      effective in lowering amyloidogenic processing. To examine the effects of
      estrogen withdrawal and replacement on amyloid beta (Abeta) levels and amyloid
      beta-protein precursor (AbetaPP) processing in vivo, Swedish mutant AbetaPP
      transgenic mice were ovariectomized or sham ovariectomized at four weeks of age
      and treated with placebo or 17beta- or 17alpha-estradiol pellets, the latter
      being a weak estrogen receptor agonist. Compared to sham ovariectomized mice,
      ovariectomy with placebo did not alter Abeta levels; however, the levels of Abeta
      were decreased by 27% and 38% in mice treated with 17beta- and 17alpha-
      estradiol, respectively, with no change in AbetaPP holoprotein. Endogenous and
      exogenous estrogen both significantly increased the levels of sAbetaPPalpha, the
      secreted form of AbetaPP. The ratio of Abeta/sAbetaPPalpha, a measure of
      amyloidogenic processing, was reduced in all estrogen-containing groups. The
      Abeta lowering effect of 17beta- and 17alpha-estradiol was replicated when
      estrogens were administered at a more physiological dose in the drinking water,
      or when mice were ovariectomized at three months of age. The increased efficacy
      of 17alpha-estradiol versus 17beta-estradiol may help to develop safe and
      effective therapeutics.

PMID- 12515897
TI  - Metallothionein I-II immunocytochemical reactivity in Binswanger's
      encephalopathy.
AB  - Binswanger's disease is a subacute form of hypertensive encephalopathy
      characterized by patchy-confluent myelin loss of the deep hemispheric white
      matter, associated with marked regressive changes of the oligodendrocytes and
      variable astroglial reaction. To understand the distribution and the specificity
      of astrocyte pathology in Binswanger's disease we quantified reactive and
      degenerating astrocytes in different regions of the deep and subcortical white
      matter and of the cerebral cortex. Sections of frontal, temporal, parietal, and
      occipital lobes of 12 histologically proven cases of Binswanger's disease were
      immunostained with antibodies to glial fibrillary protein (GFAP) and to
      metallothionein I and II (MT-I-II), markers which specifically identify normal
      and reactive astrocytes. Control tissues were from 6 elderly patients without
      neurological diseases. The brains of Binswanger's disease were characterized by
      few and lightly immunostained astrocytes in the deep white matter, but normal and
      reactive astrocytes, strongly immunoreactive for GFAP and MT-I-II, were prominent
      in the subcortical white matter and the cerebral cortex. However, the relative
      distribution of GFAP positive and MT-I-II positive astrocytes was significantly
      different between the cerebral cortex and the subcortical white matter, the MT-I
      II positive astrocytes being more frequent in the cerebral cortex, and the GFAP
      positive astrocytes in the subcortical white matter (p < 0.02). The GFAP and MT-I
      II expressions in subsets of reactive astrocytes in the cortico-subcortical
      layers together with regressive astroglial changes in the deep white matter
      suggest that the dynamic plasticity of astroglia is topographically and
      biochemically differentiated in vascular dementia of Binswanger type.

PMID- 12515898
TI  - Mechanisms of peripheral microvascular dysfunction in transgenic mice
      overexpressing the Alzheimer's disease amyloid Abeta protein.
AB  - Freshly prepared soluble amyloid (Abeta) peptide has been reported to have
      vascular actions both in vitro and in vivo. This study was designed to examine
      the in vivo microvascular effects of beta in two skin microvascular model systems
      that might reflect possible short and long-term vascular effects of this peptide.
      Short-term vascular effects were examined using freshly prepared soluble Abeta(1
      40) peptide superfused over naive rat skin microvasculature for 15 min.
      Peripheral microvascular functional changes in 9-months-old transgenic (Tg) mice
      overexpressing soluble beta in the brain, peripheral circulation and other
      tissues, were also examined. Microvascular responses were monitored using laser
      Doppler flowmetry from the base of a blister raised on the hind footpad of the
      animals. Endothelial-dependent and independent vasodilatation responses (VD) were
      examined using acetylcholine (ACh) and sodium nitroprusside (SNP) respectively.
      The exposure of naive rat skin microvasculature to Abeta(1-40) resulted in an
      immediate vasoconstriction (VC) that prevented ACh but not SNP from inducing a
      subsequent VD response. The vascular effects of Abeta(1-40) were reversed by
      antioxidants (superoxide dismutase and catalase) and an endothelin A (ETA)
      receptor antagonist (BQ-123). Tg mice overexpressing soluble Abeta and C100
      showed significant reductions in both endothelial-dependent and endothelial
      independent VD that were also reversed by antioxidants and BQ-123. In conclusion,
      this study provided evidence to support the notion of peripheral vascular effects
      of Abeta in vivo and present novel evidence for alterations in endothelial and
      smooth muscle cell function in peripheral skin microvasculature in Tg mice
      overexpressing Abeta and C100. We suggest that skin microvasculature is a useful
      model to examine the mechanisms underlying the vascular actions of the Abeta
      protein.

PMID- 12515899
TI  - Deficiency of chaperonin 60 in Down's syndrome.
AB  - Patients with Down syndrome (DS) and Alzheimer's disease (AD) share a number of
      characteristic neuropathologic lesions. Several lines of evidence suggest that
      mitochondria and the oxidative stress response are involved in the pathogenesis
      of both conditions. In the process of investigating the stress response in DS, we
      discovered a defective basal expression of a major mitochondrial heat shock
      protein, chaperonin 60 (Cpn60) in non-transformed dermal fibroblast cell lines
      from DS individuals. Such a defect was not present in control cells that had been
      cultured under identical physiological growth conditions. A quantitative analysis
      by Western blots showed a marked reduction of Cpn60 per equal amount of total
      protein in DS cells to an average of 35% of normal. Northern blot studies
      confirmed the defect and also showed a marked reduction of the mRNA signal for
      Cpn60 in all the DS cell lines. To gain further information, experiments were
      conducted to study the rate of de-novo synthesis of Cpn60 at normal and
      supraoptimal temperatures in DS and controls. Results showed no significant
      differences between the two study groups. HSP60 is important in mitochondrial
      function and defects in these organelles have been reported in DS and AD. Thus,
      the findings may have potential implications in the neuropathology of DS.

PMID- 12515900
TI  - The glucagon-like peptides: a new genre in therapeutic targets for intervention
      in Alzheimer's disease.
AB  - Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an insulinotropic hormone,
      secreted from the enteroendocrine L cells of the intestinal tract in response to
      nutrient ingestion. It enhances pancreatic islet beta-cell proliferation and
      glucose-dependent insulin secretion, and lowers blood glucose in patients with
      type 2 diabetes mellitus. GLP-1 receptors, which are coupled to the cyclic AMP
      second messenger pathway, are expressed throughout the brains of rodents and
      humans. The chemoarchitecture of receptor distribution in the brain correlates
      well with a central role for GLP-1 in the regulation of food intake and response
      to aversive stress. We have recently reported that GLP-1 and several longer
      acting analogs that bind at the GLP-1 receptor, possess neurotrophic properties,
      and offer protection against glutamate-induced apoptosis and oxidative injury in
      cultured neuronal cells. Furthermore, GLP-1 can modify processing of the amyloid
      beta- protein precursor in cell culture and dose-dependently reduces amyloid beta
      peptide levels in the brain in vivo. As such, this review discusses the known
      role of GLP-1 within the central nervous system, and considers the potential of
      GLP-1 and analogs as novel therapeutic targets for intervention in Alzheimer's
      disease (AD) and potentially other central and peripheral neurodegenerative
      conditions.

PMID- 12515901
TI  - Alzheimer's disease: how does it start?
AB  - Presently, non-genetic Alzheimer's disease (AD) is wrongly classified as a
      neurodegenerative disorder. When vascular lesions are present, AD is considered
      to be a vascular dementia. However, compelling evidence indicates that (AD) is a
      vascular disorder with neurodegenerative consequences. There is an urgent
      clinical need to ascertain the true cause of this dementia. In this review,
      evidence indicating that AD is a vascular disorder comes from a number of
      different disciplines including studies in epidemiology, pharmacology,
      neuroimaging, clinical medicine, pathology, physiology and experimental research.
      This collective evidence also addresses many previously puzzling questions
      regarding: i) past and present treatment failures in AD, ii) strange association
      of AD risk factors with many vascular-related disorders, iii) parallel lesions,
      clinical symptoms risk factors and potentially interchangeable treatments present
      in AD and vascular dementia, iv) historical difficulty in finding
      neurodegenerative markers to detect AD pre-clinically, and, v) paradoxical
      pathophysiologic events preceding AD neurodegenerative changes. Re-classifying AD
      as a vascular disorder would very likely improve the chances of finding a useful
      treatment for this disorder because clinical study designs could focus on more
      realistic and relevant pathologic targets than is presently practiced. A short
      summary of potential new research lines that may provide novel therapy in the
      treatment and management of AD is discussed.

PMID- 12515902
TI  - Is non-genetic Alzheimer's disease a vascular disorder with neurodegenerative
      consequences?

PMID- 12515903
TI  - Water quality has a pronounced effect on cholesterol-induced accumulation of
      Alzheimer amyloid beta (Abeta) in rabbit brain.
AB  - Increased circulating cholesterol is known to promote risk of coronary artery
      disease. It is now emerging that cholesterol promotes production and accumulation
      of amyloid beta (Abeta) deposited in the hallmark pathologic lesion of
      Alzheimer's disease (AD), the senile plaque, perhaps by shifting away from normal
      metabolism of amyloid beta protein precursor (AbetaPP) to beta. Previous studies
      employing the cholesterol-fed rabbit model of AD demonstrated that induction of
      AD-like Abeta accumulation in brain could be reversed by co-administration of
      cholesterol lowering drugs or removing cholesterol, prompted initiation of an AD
      Cholesterol-Lowering (Statin) Treatment Trial. We now present data that identify
      a previously unrecognized role for dietary water quality on the severity of
      neuropathology induced by elevated cholesterol. Neuronal accumulation of Abeta
      induced by increased circulating concentrations of cholesterol in the New Zealand
      white rabbit is attenuated when distilled drinking water is administered compared
      to use of tap water. The numbers of neurons in cholesterol-fed rabbits that
      exhibited Abeta immunoreactivity, relative to normal chow-fed controls, increased
      approximately 2.5 fold among animals on tap water but only approximately 1.9 fold
      among animals on distilled water. This yielded a statistically significant
      approximately 28% reduction due to the use of distilled water. In addition, the
      subjectively assessed intensity of neuronal Abeta immunoreactivity was
      consistently reduced among cholesterol-fed rabbits allowed distilled drinking
      water compared to cholesterol-fed rabbits on tap water. As intensity of antibody
      immunoreactivity is likely related to concentration of antigen, the identified
      difference among cholesterol-fed rabbits allowed distilled drinking water may
      hold greater importance than a significant reduction in numbers of affected
      neurons. The effect on neuronal Abeta immunoreactivity intensity was observable
      among cholesterol-fed rabbits reared and allowed tap water when performing
      studies in three distinct locales. Pilot data suggest the possibility of
      increased clearance of Abeta from the brain, identified as increased blood
      levels, among cholesterol-fed rabbits administered distilled water compared to
      animals on tap water. The agent(s) occurring in tap water, excluded by
      distillation, promoting accumulation of neuronal Abeta immunoreactivity is(are)
      yet undisclosed, but arsenic, manganese, aluminum, zinc, mercury, iron and
      nitrate have tentatively been excluded because they were not identifiable (below
      detection limits) in the tap water of the three locales where the cholesterol
      induced neuropathologic difference was observable. These findings suggest that
      water quality may impact on human health in the setting of increased circulating
      cholesterol levels, and could illustrate a truly simple life-style change that
      could be of benefit in AD.

PMID- 12515905
TI  - Evaluation of blood units with isolated anti HBC for the presence of HBV DNA.
AB  - We screened blood donors in one center in Saudi Arabia for a safety transfusion.
      We found that among 5043 blood donors negative for HCV and HIV, the incidence of
      HBsAg positivity was 2.97%. When antiHBc antibody was measured (HBcIg) in HBsAg
      negative donors, we observed that 21.47% were positive indicating previous
      exposure to hepatitis B virus. The HBcIg positive blood was further screened for
      HBsAb and the specimens were found to be reactive in 81.54%. Based on these data
      blood transfusion was permissible from donors who showed HBsAg negativity, HBcIg
      positive and HBsAb reactive blood. In order to ensure safety transfusion an
      aliquot of specimens (n = 80) was further analyzed for HBV DNA by PCR. We found
      only one specimen positive with incidence of 1.25%. So we recommended restricting
      transfusion from the previously mentioned donors to emergencies.

PMID- 12515906
TI  - Soluble inter-cellular adhesion molecule-1 in urban Asian north Indians:
      relationships with anthropometric and metabolic covariates.
AB  - BACKGROUND: High prevalence of diabetes, obesity, and dyslipidemias in people
      belonging to poor socio-economic strata in urban slums of northern India has been
      recorded recently. To assess whether this population has high levels of soluble
      intercellular adhesion molecule-1 (sICAM-1), a cytokine involved in the
      pathogenesis of atherosclerosis, we investigated subjects belonging to poor socio
      economic strata in urban slums and compared them to healthy control subjects from
      non-slum urban areas of New Delhi. DESIGN: Cross-sectional study. METHODS:
      Subjects from a previously carried out cross-sectional study, Delhi Urban Slum
      Project (DUSP) were divided into two groups: Group-1 (n = 56) included subjects
      dwelling in slum area, having at least one risk factor (hypertension,
      hyperglycemia, hypertriglyceridemia and hypercholesterolemia), while group-2 (n =
      60) consisted of subjects without any risk factor dwelling in the slum area. A
      third group (n = 29) of non-obese subjects without any risk factor living in non
      slum urban area was included for comparison. Measurements included; body mass
      index (BMI), waist-hip ratio (W-HR), four skinfolds, percentage body fat, fasting
      plasma glucose (FPG), serum lipids, and serum levels of sICAM-1. RESULTS: Though
      statistically not significant, mean level of sICAM-1 was higher in group-1 (718.5
      +/- 232.8 ng/ml) as compared to the other groups. Of note, 35% of subjects in
      group-1 (p < 0.05 as compared to other two groups), and 25.3% of all subjects had
      levels of sICAM-1 in uppermost quartile (> 850 ng/ml). Partial correlation
      coefficients (R) of sICAM-1 levels with various parameters adjusted for age were
      statistically significant for BMI (R = 0.27, p < 0.05) in group-1; W-HR (R =
      0.26, p < 0.05) and BMI (R = 0.19, p < 0.05) for group-2; and FPG (R = 0.17, p <
      0.05) for all the subjects considered together. For females, the levels of sICAM
      1 were significantly higher in the following: BMI > OR = 25 kg/m2 (p = 0.04) and
      FPG > 7 mmol/l (p < 0.05). Multiple linear regression analysis suggests that an
      increment in BMI by one kg/m2 would correspond to an increase in the levels of
      sICAM-1 by 8.5 units controlling for the influence of age and W-HR in the pooled
      data of all subjects. CONCLUSIONS: High percentage of subjects had levels of
      sICAM-1 in the upper quartile in the study, particularly those dwelling in the
      slum area and having coronary risk factor (s). The levels of sICAM-1 strongly
      correlated to the anthropometric and metabolic parameters, particularly in
      females. These observations are of potential importance for the pathogenesis of
      atherosclerosis in this population, though further studies are needed to predict
      those prone to the complications of atherosclerosis, based on sICAM-1 levels, as
      has been observed in other ethnic groups.

PMID- 12515907
TI  - The stromelysin-1 5A/6A promoter polymorphism is a disease marker for the extent
      of coronary heart disease.
AB  - BACKGROUND: Matrix metalloproteinases, such as stromelysin-1, are implicated in
      the pathogenesis of coronary artery disease (CAD) and acute myocardial infarction
      (MI). A 5A/6A promoter polymorphism can regulate the transcription of the
      stromelysin-1 gene in an allele-specific manner. Evidence has been presented that
      the 6A allele is associated with the progression of coronary heart disease (CHD).
      In contrast, the 5A allele may be linked to the risk of MI. RESULTS: To analyse
      the relation of the 5A/6A polymorphism with the risk and severity of CHD and the
      risk of MI, a case-control study of 515 healthy controls and 1848 participants
      who underwent coronary angiography for diagnostic purposes was conducted. In the
      total sample, the mean CHD scores--according to Gensini--were different between
      5A/6A genotypes: 5A5A homozygotes had the lowest, 6A6A genotypes the highest and
      5A6A heterozygotes intermediate scores. These differences were even more
      pronounced when the participants were restricted to individuals with a high
      coronary risk profile (high apoB levels, high Lp(a) levels, high glucose levels,
      combinations of either high apoB and Lp(a) levels or high apoB, Lp(a) and glucose
      plasma levels). Mean values were used as cut points for high-risk populations,
      respectively. In contrast, the 5A allele was not associated with the risk of CHD
      or MI. Even when angiographically controlled individuals without MI were compared
      with MI patients in subpopulations of participants with no, single, double and
      triple vessel disease, the frequencies of the 5A/6A and/or the 5A5A genotypes
      were not higher in each subgroup, respectively. CONCLUSIONS: The present results
      do not confirm an association of the 5A allele with the risk of MI, observed in
      another investigation, but strengthen the hypothesis of earlier studies that the
      6A allele is a disease marker for progression of coronary heart disease. Further
      investigations should evaluate whether 6A allele carriers and especially 6A
      homozygotes might benefit from a more aggressive therapy against CHD progression.

PMID- 12515908
TI  - Surfactant protein B intron 4 variation in German patients with COPD and acute
      respiratory failure.
AB  - Chronic obstructive pulmonary disease (COPD) is a major health problem. Genetic
      factors that contribute to the disease have been postulated. The pulmonary
      surfactant protein B (SP-B), which is essential for normal lung function, is
      considered as a candidate gene for COPD in this case-control study. We studied
      the SP-B intron 4 size variants in 346 individuals. This group consisted of 118
      patients with chronic bronchitis or COPD, including 24 patients with acute
      respiratory failure (ARF) in COPD, 118 matched controls without pulmonary disease
      and 110 healthy individuals (population control). The frequency of intron 4
      variants was similar in either control group (10.9%, 14.4%, respectively), with a
      small increase in the COPD group (18.6%). This increase was due to a high
      increase of intron 4 variants in the ARF subgroup (37.5%, p = 0.003, OR 4.9, 95%
      CI: 1.76-13.6). The data indicate that SP-B intron 4 variants may associate with
      increased risk of ARF in COPD and may be used as a marker of susceptibility in
      this disease subgroup.

PMID- 12515909
TI  - Evaluation of nitric oxide (NO) levels in hepatitis C virus (HCV) infection:
      relationship to schistosomiasis and liver cirrhosis among Egyptian patients.
AB  - Nitric oxide (NO), a recently discovered free radical, is overproduced in liver
      cirrhosis. Hepatitis C virus (HCV) might increase NO levels via increased
      inducible NO synthase (iNOS). This work was carried out to study the effect of
      HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study
      included 46 patients with liver cirrhosis, and 30 healthy individuals of matched
      age and sex. NO levels determined as the stable endproduct nitrate, showed a
      statistically significant increase among patients compared to the control group
      (P < 0.001). Furthermore, NO levels increased proportionally with the severity of
      liver cirrhosis as assessed by Child's classification (P < 0.05). Moreover,
      schistosomial infection enhanced NO levels in cirrhotic patients with HCV
      infection compared to non-bilharzial patients (P < 0.001). Polymerase chain
      reaction (PCR) and branched DNA assays were used for detection of HCV RNA
      positivity, and measurement of the virus load, respectively. Both showed a
      positive correlation with the NO levels (P < 0.001). At a nitrate cutoff value of
      70 micromol/L, the sensitivity and specificity were 83.0% and 73.0%,
      respectively. Chi square analysis showed a significant correlation between ALT
      levels and both HCV RNA positivity by polymerase chain reaction (PCR) (P < 0.02),
      and virus load (P<0.05). Interestingly enough, there was a significant positive
      correlation between HCV RNA and schistosomal antibody titer as measured by
      hemaglutination inhibition assay (HAI) (P < 0.05). The data presented in this
      report indicated an association between NO levels and the development and
      progression of liver cirrhosis. Furthermore, the findings obtained from this
      study demonstrated that schistomiasis is an important risk factor involved in
      enhancement of NO levels and virus replication. The latter may aggravate liver
      cell injury and hence the development of cirrhosis.

PMID- 12515910
TI  - Immunohistochemical expression of Retinoblastoma gene product in normal,
      hyperplastic and malignant endometrium. Correlation with p53 protein expression,
      c-erbB-2, hormone receptors' status and proliferative activity.
AB  - Alterations of the retinoblastoma (Rb) gene have been described in several human
      neoplasms and recently, it has been suggested that these alterations may play a
      role in the development of endometrial carcinomas. Paraffin sections from 31
      cases of normal endometrium (16 proliferative, 15 secretory), 35 hyperplastic
      lesions and 89 endometrial carcinomas were investigated immunohistochemically for
      Rb protein (pRb) expression. The results were compared with p53 and c-erbB-2
      protein expression, estrogen (ER) and progesterone (PR) receptors' status and
      with clinicopathological prognostic factors. pRb was expressed in normal,
      hyperplastic and neoplastic epithelium. Proliferative endometrium showed more
      intense and extensive pRb staining than secretory endometrium. pRb reactivity was
      heterogeneous in the hyperplastic endometrial cells. Lack or focal (< 10% of
      endometrial cells) pRb immunostaining was noted in 56.2% and 27% of carcinomas,
      respectively. In the remaining cases (16.8%) pRb staining was heterogeneous or
      diffuse. The absence or presence of pRb expression was independent of grade and
      stage. In normal proliferative and secretory endometrium, pRb expression was
      correlated with PR (p = 0.006 and p = 0.001, respectively), PCNA (p = 0.04 and p
      = 0.01, respectively) and MIB1 (p = 0.02 and p<0.0001, respectively) expression.
      In hyperplasias, pRb was related to PR (p = 0.016) and MIB1 (p < 0.0001)
      expression. In carcinomas, a relationship of pRb expression with p53 (p =
      0.0015), ER (p = 0.0002), PR (p = 0.0004) and PCNA (p = 0.013) status was
      detected. We suggest that the absence or presence of pRb expression does not seem
      to be associated with the progression of endometrioid carcinoma. In addition, pRb
      seems to be normally regulated in relation to the proliferative growth fraction
      of the tumours.

PMID- 12515911
TI  - Hepatocyte proliferation factors from neonatal pig liver: purification and
      characterization.
AB  - Two factors were found in the condition medium of neonatal pig liver fragments,
      which were capable of stimulating DNA synthesis in primary hepatocytes. They were
      named hepatocyte proliferation factor (HPF)-1 and HPF-2 and purified 1,025- and
      2,580-fold, respectively. Both HPF-1 and HPF-2 seem to be anionic at pH 8.0
      judged from the elution pattern of DEAE (DE52) column chromatography. HPF-1 was
      recovered as a non-adsorbed fraction in blue Sepharose and heparin Sepharose
      columns, and had a molecular weight of 26-31 kDa as estimated by gel filtration
      in high salt condition. Purified HPF-1 stimulated DNA synthesis of primary rat
      hepatocytes, but suppressed that of HepG2 cells. HPF-2 strongly bound to blue
      Sepharose and heparin Sepharose columns, and had a molecular weight of 71-90 kDa
      as estimated by SDS-PAGE under non-reduced condition. Purified HPF-2 stimulated
      DNA synthesis of primary rat hepatocytes dose dependently but did not suppress
      that of HepG2 cells. From further biological and chemical characteristics studied
      in this paper, HPF-1 and HPF-2 may be novel stimulating proteins for hepatocyte
      proliferation, although the possibility that they are already known growth
      factors can not be excluded without complete purification and its cloning.

PMID- 12515912
TI  - Diesel exhaust particles induce an inflammatory response in airway epithelial
      cells: involvement of reactive oxygen species.

PMID- 12515913
TI  - Transport of methotrexate into LNCaP human prostate cancer cells.
AB  - Uptake of methotrexate into the LNCaP human prostate cancer cells was linear for
      the first 60 min. The initial rate of methotrexate uptake was highest at
      extracellular pH 4.5 and decreased markedly until pH 7.0 to 8.0. Transport of
      methotrexate into LNCaP cells showed two components, one saturable -K(m) = 0.13
      +/- 0.06 microM and V(max) = 1.20 +/- 0.16 pmol x 45 min(-1) x mg(-1) protein at
      low concentrations and the other apparently not saturable up to 10 microM. Uptake
      of methotrexate was inhibited by structural analogs with the K(i) values being
      6.53, 12.4, and 85.6 microM for 5-formyltetrahydrofolate, 5
      methyltetrahydrofolate, and folic acid, respectively. Uptake of methotrexate into
      LNCaP cells was not inhibited by the energy poisons in contrast to methotrexate
      uptake into PC-3 prostate cancer cells. Uptake was inhibited by increasing
      concentrations of sulfate and phosphate ions and by the organic anions probenecid
      and DIDS, suggesting that methotrexate may be transported by an anion-exchange
      mechanism. These results show that methotrexate is transported into LNCaP
      prostate cancer cells by a carrier-mediated process.

PMID- 12515914
TI  - Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide
      synthase during impaired wound healing.
AB  - Wound healing is a highly ordered process, requiring complex and coordinated
      interactions involving peptide growth factors of which transforming growth factor
      beta (TGF-beta) is one of the most important. Nitric oxide is also an important
      factor in healing and its production is regulated by inducible nitric oxide
      synthase (iNOS). We have earlier shown that curcumin (diferuloylmethane), a
      natural product obtained from the plant Curcuma longa, enhances cutaneous wound
      healing in normal and diabetic rats. In this study, we have investigated the
      effect of curcumin treatment by topical application in dexamethasone-impaired
      cutaneous healing in a full thickness punch wound model in rats. We assessed
      healing in terms of histology, morphometry, and collagenization on the fourth and
      seventh days post-wounding and analyzed the regulation of TGF-beta1, its
      receptors type I (tIrc) and type II (tIIrc) and iNOS. Curcumin significantly
      accelerated healing of wounds with or without dexamethasone treatment as revealed
      by a reduction in the wound width and gap length compared to controls. Curcumin
      treatment resulted in the enhanced expression of TGF-beta1 and TGF-beta tIIrc in
      both normal and impaired healing wounds as revealed by immunohistochemistry.
      Macrophages in the wound bed showed an enhanced expression of TGF-beta1 mRNA in
      curcumin treated wounds as evidenced by in situ hybridization. However, enhanced
      expression of TGF-beta tIrc by curcumin treatment observed only in dexamethasone
      impaired wounds at the 7th day post-wounding. iNOS levels were increased
      following curcumin treatment in unimpaired wounds, but not so in the
      dexamethasone-impaired wounds. The study indicates an enhancement in
      dexamethasone impaired wound repair by topical curcumin and its differential
      regulatory effect on TGF-beta1, it's receptors and iNOS in this cutaneous wound
      healing model.

PMID- 12515916
TI  - Get involved! How to pass NP legislation in your state.

PMID- 12515917
TI  - Advance your career on-line.

PMID- 12515918
TI  - Match the best smoking cessation intervention to your patient.
AB  - Various treatment modalities and programs provide smoking cessation aid, but how
      effective are each of these treatment options? Select the optimum treatment for
      your patient by learning the efficacy and applicability of interventions such as
      counseling, nicotine replacement therapy, non-nicotine drugs, harm reduction, and
      acupuncture.

PMID- 12515919
TI  - Jump on the PDA bandwagon.

PMID- 12515920
TI  - [Threats on vaccination?].

PMID- 12515921
TI  - [Analysis of an apparent cluster of Crohn's disease cases in Indre-et-Loire,
      France (1990-1999)].
AB  - BACKGROUND: Four cases of Crohn disease (CD) were diagnosed between 1990 and 1997
      in children living in the same area in the Indre-et-Loire district (county A).
      The local population raised the hypothesis that an environmental source could be
      responsible for these cases. An investigation was carried out to assess the
      excess of cases and to identify their possible determinants. METHODS: A case was
      defined as any new case of CD (European definition) that occurred between 1989
      and 1998 in county A or in the adjacent county of the Vienne district. Case
      finding was done by contacting all hospital services, pediatricians and gastro
      enterologists in the 2 districts. A Standardized Incidence Rate (SIR) was
      calculated for sex and age in adults and children using data from the
      Inflammatory Bowel Registry of northern France. Statistical significance was
      assessed by a test taking into account small samples. A descriptive study was
      carried out among pediatric cases. RESULTS: Four pediatric cases and four adults
      were identified, all from county A. The SIR in adults was 0,45 (95% Confidence
      Interval [95% CI: 0.12-1.15). In children, the global SIR was 8,51 (95% CI: 2.29
      21.79) and 19,05 (95% CI: 5.12-48.70) in county A. The descriptive study did not
      identify any exposure leading to a possible hypothesis concerning the origin of
      the cases. CONCLUSION: This study has shown that the incidence of CD among
      children of the area was greater than observed in France and has permitted to
      establish a close relationship with the affected families, to implement a social
      approach to the problem and to limit rumors. It illustrates the interest of a
      systematic stepwise approach, which takes into consideration the anxiety of the
      local community. Cluster investigation should be integrated as part of the public
      health agencies activities. However, in most cases, despite an excess risk,
      results do not allow to conclude in terms of etiology.

PMID- 12515922
TI  - [Prevalence of exercise-induced asthma in school children].
AB  - BACKGROUND: Although asthma is the most common pulmonary condition in pediatrics,
      the incidence of exercise-induced asthma (EIA) in school children is not well
      documented and few studies have been devoted to the condition. There are
      considerable variations in morbidity and mortality between countries. This study
      was designed to evaluate the prevalence of EIA in children in the 6th grade (11
      14 year-olds) in one French department (Haute-Vienne) and to identify undiagnosed
      cases. METHODS: The representative sample was obtained over a period of 28 days
      (February 2(nd) to April 10(th) 1998) by cluster sampling method, stratified by
      size of the schools. The number of subjects planned was 891. The selected
      children filled in a questionnaire on their asthma history and were subjected to
      an outdoor exercise test (6 minute run). Respiratory function was measured with a
      peak flow-meter. RESULTS: Seven hundred and eighty two school children were
      included in this survey. Participation rate was 87.8%. The prevalence of asthma
      from the questionnaire was 10.7% (CI 95%: 8.7 - 12.8). After exercise, 68 school
      children presented exercise-induced bronchospasm: the prevalence of the EIA was
      8.7% (CI 95%: 6.9 - 10.5). Among these 68 school children, 27 were known
      asthmatics and 41 were not. With the 10 treated asthmatics, the overall
      prevalence of EIA was therefore estimated at 9.9% (CI 95%: 8.2 - 11.7).
      CONCLUSION: The prevalence of asthma and EIA was close to that found in other
      studies using a similar methodology. EIA remains under-diagnosed since 41
      undeclared asthmatic school children were identified in our population.
      Nurses'information is necessary to initiate the use of systematically testing
      respiratory function (with a peak flow meter) at least once a year. Efficient
      management of the asthmatic child requires cooperation between the various
      professionals dealing with school children.

PMID- 12515923
TI  - [Food habits, physical activity and overweight among adolescents].
AB  - BACKGROUND: Overweight and obesity prevalence is increasing worldwide. Not only
      adults but also children and adolescents are involved. There are no recent data
      from French West Indies, where situation is believed to be worrying. Hence, the
      objective of the study was to provide information on the situation of
      adolescents, describing their nutritional status, food consumption and physical
      activity habits. METHODS: A sample of adolescents of both sexes, 14 to 15 years
      of age, was drawn among the 45 secondary schools of the Island. Of 993
      adolescents drawn, 715 participated in the study which consisted in a
      questionnaire on their food and physical activity habits and anthropometric
      measurements. RESULTS: As a whole these adolescents displayed a greater growth
      rate than the WHO reference population. About 20% presented a body mass index
      (BMI) over the chosen thresholds for overweight and obesity. They were slightly
      more mature than the French Continental children (i. e. girls experienced
      menarche at 11.9 +/- 1.0 years of age versus 13 years in Metropolitan France).
      Their food habits were similar in structure and composition, to those of
      westernised countries, while retaining some features of the "Creole culture".
      Foods rich in animal fats and carbohydrates were prevailing. Girls ate less dairy
      products than boys (53% of the adolescent girls drank milk during breakfast
      against 64% of the boys). Almost every boy had a sport activity out of school,
      but girls were less often enrolled in sports. Sport activity decreased with age.
      There were no clear differences in physical activity levels between adolescents
      with high BMI or low BMI. CONCLUSIONS: There is an excess of overweight and
      obesity in this adolescent population. These conditions may have appeared soon
      during childhood and be hardly modified latter. Physical activity level would
      have a stronger impact on fatness during childhood than at adolescence. Hence, a
      special attention should be brought early to the nutritional status, food and
      physical activity habits of young children, given the risks to develop
      degenerative diseases when adults.

PMID- 12515924
TI  - [Food habits, physical activity and overweight among adolescents. Comment: from
      knowledge to public health programme].

PMID- 12515925
TI  - [Geography of French alcohol consumption].
AB  - BACKGROUND: Alcohol consumption is still a major public health problem in France.
      A recent survey in the general population provided an overall picture of regional
      differences of alcohol consumption and demonstrated the difficulty encountered in
      comparing declarative data and economic and health data. METHODS: A method based
      on standardisation was applied to control the effects of age and gender in order
      to demonstrate regional differences in daily alcohol intake and episodes of
      drunkenness during the year as well as differences in weekly alcohol intake. A
      hierarchical clustering was performed based on these indicators in order to
      obtain a regional map. RESULTS: Three classes of regions were distinguished. The
      first group included regions where the prevalence of drunkenness or alcohol
      intake was particularly high (Brittany, Pays de la Loire, Burgundy, Alsace,
      Franche-Comte, Rhone-Alpes). The second group included regions where daily
      consumption was frequent and rather high in quantity (Limousin, Auvergne,
      Aquitaine, Midi-Pyrenees, Languedoc-Roussillon). The third group included regions
      where daily intake and drunkenness were exceptional. These results were compared
      with external data: household data, alcohol-related mortality data, medical
      consultation data. In some regions in southwestern France or northern France,
      results showed a poor fit between economic and social data. CONCLUSION: Measuring
      the quality of declarative data on alcohol consumption is essential for public
      health decision-makers. Comparing economic and sanitary data remains a difficult
      task. Differences related to the source of the data lead to very different
      concepts of the problem, requiring in-depth knowledge and new hypotheses to
      correctly interpret such differences. Further work is needed to better ascertain
      the different aspects of the problem of alcohol consumption in France. For
      example, general population surveys might include more precise questions for
      identifying excessive drinkers or questions on economic data related to alcohol
      (e.g. purchasing practices).

PMID- 12515926
TI  - [Prior use of a telephone-nursing triage service by patients of emergency
      services].
AB  - OBJECTIVES: A province-wide telephone-nursing triage service was implemented in
      Quebec, Canada, in order, among other objectives, to decrease overcrowding in
      hospital emergency rooms. This study analyses prior use of Info-Sante CLSC
      telephone service by patients of emergency services. METHODS: Structured
      interviews were conducted with 850 patients of a general hospital emergency room
      and of walk-in medical clinics. Patients were recruited while waiting to see the
      physician between 8h and 23 h, 7 days a week, from November 1997 to June 1998.
      Information was collected on knowledge and use of the telephone-nursing triage
      service, health problem and perceived health status, information-seeking
      behaviour on health services, utilisation habits, social support, and socio
      demographic characteristics. Interval estimates and multiple logistic regressions
      were performed. RESULTS: Of the patients who were aware of this service, 17,4%
      (CI(95)=0,14 - 0,20) had used it prior to their medical visit. Among these, 85,1%
      had received a recommendation to consult a doctor. Among the users who were at
      the hospital emergency room at the time of the study, 56,4% were advised to
      consult a walk-in clinic or a CLSC, 28,2% their family doctor and only 12,8% a
      hospital emergency room. The probability of prior recourse to the telephone
      nursing service is influenced significantly by the duration of the health problem
      (2-4 days versus<2 days: OR(adjusted)=2,03), new health problem
      (OR(adjusted)=1,98) and by the frequenting of walk-in clinics rather than
      hospital emergency rooms (OR(adjusted)=0,31). CONCLUSION: Despite a heightened
      awareness of the telephone-nursing triage service, few users of emergency
      services make use of it and, when they do, follow rather loosely the
      recommendation towards the type of service judged appropriate for their needs.

PMID- 12515927
TI  - Sensitivity of ultrasound screening for congenital anomalies in unselected
      pregnancies.
AB  - OBJECTIVE: To assess the influence of heart defect frequency and severity on
      screening sensitivity of the entire spectrum of congenital anomalies (CA) and on
      detection rate of congenital heart defect (CHD) when performing routine
      ultrasound screening in unselected pregnant women. STUDY DESIGN: Secondary
      analysis was performed on data from Eurofetus, a large international
      collaborative study of ultrasound screening for CA in unselected populations. The
      present study addressed the relations (i) between the frequency of CHD in the
      screened population and the global sensitivity of ultrasound in detecting CA;
      (ii) between frequency of ventricular septum defect (VSD) and detection rate of
      CA and CHD; and (iii) between seriousness of CHD and CHD sensitivity. RESULTS: A
      negative correlation (p<0.001) between CHD frequency and CA sensitivity was
      observed in this study. Likewise, a negative correlation was also found between
      frequency of VSD and sensitivity for CA or CHD detection (p<0.001). In addition,
      a positive significant relationship (p<0.001) was observed between sensitivity
      and severity of CHD. CONCLUSION: A low CHD frequency introduces bias in CA and
      CHD sensitivity evaluation. Incomplete assessment of fetal and neonatal
      malformations brings on systematic error, leading to the pre-eminence of severe
      defects in the studied population sample and artificially improving sensitivity
      figures. On the other hand, from a clinician's viewpoint, the higher sensitivity
      for severe defect is welcomed, since their detection is most crucial for
      appropriate management.

PMID- 12515928
TI  - [Macro-economic calculation of spending versus micro-economic follow-up of costs
      of breast cancer].
AB  - BACKGROUND: In the healthcare field, the ability to make economic forecasts
      requires knowledge of the costs of caring for major diseases. In the case of a
      semi-chronic condition like cancer, this cost covers all the episodes of care
      associated with a patient. An evaluation of a macro-economic method of
      calculating costs for treating non-metastatic cancer, covering all hospital
      episodes, is proposed. This method is based entirely on the use of annual
      hospital activity databases, linked to data concerning the incidence of cancer.
      It allows us to obtain the global cost of care for a neoplasm of a particular
      site, without the need to reconstruct the whole care pathway of the patients.
      METHODS: The model was assessed by comparing it's own results, in the particular
      case of breast cancer to those issuing from a micro-economic follow-up of 115
      patients. Data for macro-economic calculation are extracted from the national
      French hospital database for the year 1999 and from cancer incidence data. The
      prospective study was done in 1995, in a comprehensive cancer centre. RESULTS:
      Macro-economic calculation leads to a cost of 14,555 Euro, for primary breast
      cancer. Prospective follow-up showed a cost of 14,350 Euro (data corrected, 1999
      value). With a difference of 1%, there was a clear cohesion of the two results,
      while a higher level of divergence was noticed (from 1 to 15%) in the comparison
      between therapeutic techniques. Accuracy and reliability of results were
      evaluated. CONCLUSION: This method may be extended to all types of neoplasms.
      This method cannot be used instead of follow-up studies, for cost-efficacy or
      cost-severity analysis, but may be interesting beyond economic forecasts, in the
      field of payment per pathology.

PMID- 12515929
TI  - [Quality of medical database to valorize the DRG model by ISA cost indicators].
AB  - BACKGROUND: The use of the French version of the DRG model is focused on cost
      allocation, based on the case-mix system and the use a weight called ISA
      (Synthetic Index of Activity) for each DRG. However, this administrative database
      is becoming more and more used by both researchers and health policy makers for
      health planning and benchmarking. In France, data abstraction and coding of
      medical records is done by physicians. The objective of this study was to
      determine the accuracy of a database of the discharge summaries used for DRGs and
      to compare consequences of inappropriate coding on budget estimation and risk
      adjustment. METHODS: Samples of discharge summaries from six cardiology units
      were recoded by trained physicians in data abstracting and coding. Comparison
      between initial and recoded diagnoses (errors on main diagnosis or on
      comorbidities) used by the DRG system algorithm, and the original and final case
      mix were performed. The before and after abstracted data were stratified and
      compared by principal diagnosis (myocardial infarction or congestive heart
      failure) and discharge status (dead or alive). MAIN RESULTS: Comorbidities were
      underreported by physicians of cardiology units compared to reabstracted data
      (mean number of secondary diagnoses per summary: 2.1 vs. 3.6, p<0.001),
      especially those which had a minimal impact on the DRG classification. In spite
      of a 15% rate of wrong DRGs, there was no significant difference in the total
      amount of ISA after data reviewing. Underreporting of comorbidities is more
      important for medical records of dead patients at discharge but, without
      significant effect on rate of change in DRG and amount of ISA. CONCLUSION:
      Discharge summaries used in the French DRGs system consistently underestimate the
      presence of comorbid conditions, which has direct implications for policy-makers
      comparing performance between hospital units. Both clinical practitioners and
      policy makers should be aware of this bias when assessing patient's quality of
      care or performing health planning through discharge summaries.

PMID- 12515930
TI  - [Tobacco use in the schools of Doubs (France), ten years after the "Evin law"].

PMID- 12515931
TI  - [Amniotic membrane transplantation in severe corneal epithelial diseases.
      Preliminary results].
AB  - PURPOSE: To evaluate amniotic membrane transplantation (AMT) in severe corneal
      epithelial diseases. METHODS: Amniotic membrane transplantation was performed in
      14 eyes of 14 patients from four groups: A, five severe ocular burns; B, four
      cases of cicatricial keratoconjunctivitis; C, three persistent epithelial defects
      after penetrating keratoplasty; D, two cases of pseudophakic bullous keratopathy.
      Five patients underwent AMT alone; two patients underwent AMT combined with
      limbal transplantation; the other three patients had limbal transplantation
      performed before AMT. Eight patients required combined penetrating keratoplasty.
      Patients with corneal stable reepithelialization, no corneal neovascularization,
      and no recurrence of the initial pathology were considered successful. RESULTS:
      The mean follow-up was 7+/-3 months. All but three patients underwent corneal
      reepithelialization within 6 weeks of AMT, with a mean healing time of 31+/-23
      days. The success rate was 75% at 6 months (Kaplan-Meier method). Three of four
      procedures in group B failed. In eight patients, visual acuity improved, in one
      it worsened, and in the last five patients it remained unchanged. Visual acuity
      increased by an average of 7+/-9 lines. CONCLUSION: AMT is a useful technique for
      ocular surface reconstruction, especially in association with limbal
      transplantation. It could also improve the prognosis of penetrating keratoplasty
      in patients with severe corneal conditions.

PMID- 12515932
TI  - [Fungal keratitis at the Centre Hospitalier National d'Ophtalmologie des Quinze
      Vingts: retrospective study of 19 cases].
AB  - PURPOSE: To report the spectrum of fungal keratitis at the Centre Hospitalier
      National d'Ophtalmologie XV-XX, Paris. METHODS: We reviewed 19 cases of fungal
      keratitis from January 1993 to January 2001. We evaluated the different risk
      factors, fungal identification, topical and systemic antifungal therapy, surgical
      treatment and outcome. RESULTS: Nineteen patients were included, 7 women and 12
      men, with visual acuity ranging from 9/10 to no perception of light. The mean age
      was 56.2 years. Patients were hospitalized for an average stay of 16.3 days and
      all received a diagnostic and therapeutic scraping and 16 received a local
      antifungal treatment. The most common risk factors were topical steroid treatment
      (42.1%), corneal graft (31.6%), trauma or foreign body (31.6%). The mean delay
      between the first signs and fungal keratitis diagnosis was 14 days. Yeast as
      Candida parapsilosis and albicans were the most frequently isolated fungi (58%),
      followed by Aspergillus sp. (21%) and Fusarium sp. (21%). The most commonly used
      topical treatment was amphotericin B, and itraconazole was used as systemic
      treatment. Five patients had evisceration, 6 had penetrating keratoplasty and 5
      retained leukoma. CONCLUSION: Candida was the most frequently isolated fungi and
      topical steroid treatment the main risk factor. The prognosis is relatively poor
      (26% of lost vision) because of a delay in diagnosis and other previous ocular
      pathology or surgery.

PMID- 12515933
TI  - [Circulatory consequences of retinal vein occlusions. Advantages of dynamic
      angiography].
AB  - PURPOSE: To compare angiographic features in patients with branch vein (BRVO) and
      central retinal vein occlusion (CRVO) and to discuss their possible significance.
      PATIENTS AND METHODS: Clinical and indocyanine green (ICG) videoangiographic data
      of 35 patients with CRVO and 5 patients with BRVO were reviewed. In order to more
      fully understand the significance of hemodynamic alterations, patients with a
      decrease in retinal flow velocity from other causes (optic neuritis, carotid
      cavernous fistula, carotid artery stenosis) were compared to patients with vein
      occlusion. RESULTS: Whatever the type of occlusion, the most frequent abnormality
      was the presence of pulsatile venular outflow, which at the acute phase was
      present in the majority of cases. The decrease in arterial velocity was
      visualized by the presence of diastolic reversed flow. There was no correlation
      between visual prognosis and hemodynamic alterations. Apart from vein occlusion,
      the pulsatile venular outflow was present in situations where increased venous
      pressure was present. CONCLUSIONS: BRVO and CRVO have similar alterations of
      venous flow. Videoangiography can electively show pulsatile venular outflow and
      reverse diastolic arterial flow, and thus contributes additional information to
      conventional angiography. Pulsatile venular outflow is probably due to a
      combination of elevated venous pressure and decreased plasma velocity.
      Videoangiography provides new insight to the consequences of retinal vein
      occlusion and will possibly lead to a better understanding of the sequence of
      events that lead to visual loss.

PMID- 12515934
TI  - [Childhood Behcet's disease: clinical and evolutive aspects. About 13 cases].
AB  - INTRODUCTION: Behcet's disease is a systemic vasculitis which rarely occurs in
      childhood. The aim of this study was to evaluate clinical characteristics and
      outcome of Behcet's disease in Moroccan children. MATERIAL AND METHODS: A
      retrospective study of 13 cases of children, 10 males and 3 females with Behcet's
      disease followed up between 1990 and 1998. The diagnosis of Behcet's disease was
      based on the criteria of the international study group for Behcet's disease. All
      patients were studied by a complete clinical, ophthalmological and laboratory
      staging and treated with appropriate therapy. RESULTS: The mean age at diagnosis
      of Behcet's disease was 13.9 years. Familial forms were found in 30.7% of cases.
      Oral aphtae were noted in all cases while genital ulcers were present in 76% of
      cases. Cutaneous lesions were found in only 1 case and 53.8% of children had a
      pathergy test. Articular involvement was found in 30.7%, neurological features in
      46% and vascular manifestations in 38.4%. Only one case of intestinal involvement
      was noted. Ocular features (76%) were bilateral in all cases and were dominated
      by panuveitis complicated by macular edema ant retinal vasculitis. CONCLUSION:
      Behcet's disease seems to have particular characteristics in childhood. Familial
      forms, articular and digestive manifestations appear to be more frequent in early
      stages of Behcet's disease in children. Neurological and vascular involvement
      with panuveitis seems more frequent in the older children.

PMID- 12515935
TI  - [Laser epithelial keratomileusis for the treatment of low to moderate myopia:
      preliminary results].
AB  - PURPOSE: To analyze the refractive outcome and the postoperative pain and corneal
      haze following laser epithelial keratomileusis (LASEK) for the treatment of low
      to moderate myopia. METHODS: A monocentric prospective noncomparative study was
      started in June 2000, after informed consent was obtained from patients with a
      spherical equivalent of less than -5 diopters (D). This study actually was part
      of another prospective comparative study where the contralateral eye underwent
      photorefractive keratectomy. An epithelial debridement was performed using
      diluted ethanol, the epithelial flap was lifted, photoablation was performed, the
      flap was put back in place, and secured by a bandage contact lens. The refractive
      outcome was assessed, and postoperative pain and haze were graded using an
      analogical visual scale from 0 to 10 and a scale of 0 to 4, respectively.
      RESULTS: We included 17 eyes of 16 patients. LASEK was performed successfully in
      15 eyes (88.2%). One of these eyes could not be assessed for the refractive
      outcome and postoperative haze because the epithelial flap was torn during
      contact lens removal. The mean postoperative pain level during the night
      following the procedure was 5.7+/-2.0. The mean preoperative spherical equivalent
      (SE) was -2.5+/-1.0 D, and after a 2-month follow-up, the mean postoperative SE
      was +0.26+/-0.6 D. Twelve eyes (85.7%) and 10 eyes (71.4%) were within +/-1.0 D
      and +/-0.5 D from the attempted correction, respectively. The corneal haze grade
      was less than 1 in 12 eyes (85.7%) and equal to 1 in two eyes (14.3%). No
      complications and no loss of postoperative best-corrected visual acuity were
      noted. CONCLUSIONS: LASEK appears to be a reliable and reproducible technique for
      the treatment of myopia-associated SE of less than -5 D. Postoperative pain is
      moderate and flap-related complications of LASIK are avoided.

PMID- 12515936
TI  - [Contribution of intravitreal infracyanine green to macular hole and epimacular
      membrane surgery: preliminary study].
AB  - PURPOSE: To evaluate the contribution of intravitreal infracyanine green to
      macular hole and epimacular membrane surgery. PATIENTS AND METHODS: Twenty-five
      consecutive patients were operated on for macular hole (seven cases) or
      epiretinal membrane (18 cases) using intravitreal infracyanine. In most cases,
      25mg of infracyanine powder was diluted in 5ml of solvent, then in 5ml of BSS and
      used within 1 hour. The solution was injected at the end of the vitrectomy and
      aspirated after 1-2 minutes. The internal limiting membrane was removed in both
      diseases. All specimens were studied using confocal microscopy or an
      immunocytochemical preparation. RESULTS: In cases of macular hole, the internal
      limiting membrane was bright green colored. Opening and peeling were greatly
      facilitated. In cases of epiretinal membrane, staining was variable: the most
      frequent aspect was an uncolored central area similar to a geographic map
      surrounded by a green stained zone. Sometimes the coloration appeared as sparse
      spots on the posterior pole. Occasionally the staining was homogeneous as in the
      macular hole cases. After the removal of the membrane, a second injection made it
      possible to check for the persistence of the internal limiting membrane and
      proceed to its ablation when necessary. A good correlation was found between
      surgical and histopathological aspects. CONCLUSION: Intravitreal infracyanine
      green is very helpful for the removal of internal limiting membrane in macular
      holes and epiretinal membrane surgery.

PMID- 12515937
TI  - [Tenotoxic potential of fluoroquinolones in the choice of surgical antibiotic
      prophylaxis in ophthalmology].
AB  - PURPOSE: Fluoroquinolones are mainly used in ophthalmic antibiotic prophylaxis
      because of their broad spectrum activity and good ocular diffusion. But a single
      oral dose of fluoroquinolones can result in a serious source of tendinopathy and
      tendon rupture, especially in patients 60 years and older. It seems very
      important to investigate tendon toxicity of fluoroquinolones to improve the risk
      benefit ratio in ophthalmologic antibiotic prophylaxis. MATERIAL: and methods:
      The intrinsic tenotoxic potential of four fluoroquinolones (pefloxacin,
      ofloxacin, ciprofloxacin, levofloxacin) was directly evaluated on living adherent
      tendon cells in microplates. Cell viability and reactive oxygen species
      production was evaluated using neutral red, alamar blue, and dichlorofluorescin
      diacetate tests. RESULTS: Results showed a loss of viability associated with free
      radical production depending on fluoroquinolone molecules. Pefloxacin appeared
      more tenotoxic but no study has confirmed its efficacy in surgical antibiotic
      prophylaxis and its use in the patient who is 60 years and older could be
      disputed. Ciprofloxacin is highly toxic with a low ocular diffusion and seems to
      be inappropriate for antibiotic prophylaxis. Ofloxacin and levofloxacin are less
      cytotoxic, associated with good ocular diffusion and a broad antibacterial
      spectrum. CONCLUSION: Ofloxacin and levofloxacin seem to be good alternatives for
      improving the risk-benefit ratio in surgical antibiotic prophylaxis in patients
      60 years and older.

PMID- 12515938
TI  - [Emergencies in nontraumatic orbital diseases].
AB  - INTRODUCTION: Nontraumatic orbital diseases only exceptionally require emergency
      treatment. In this paper an emergency is considered when the diagnosis and/or
      treatment must be done within a maximal period of 1 week. MATERIALS AND METHODS:
      All patients with nontraumatic orbital diseases from the Department of
      Ophthalmology of the University of Lausanne and from the office of one of the
      authors (N.D.) over the last 35 years were studied, in view of their degree of
      emergency. Data from 77 patients (28 females and 49 males), aged from birth to 85
      years, were collected. RESULTS: Idiopathic inflammations of the orbit
      (pseudotumors) were the most frequent diagnoses seen as an emergency, followed by
      rhinological diseases with orbital consequences (exteriorized sinusitis or
      mucoceles), dysthyroid orbital pathologies, bleeding in lymphangiomas and
      varices, rhabdomyosarcoma, and acute dacryoadenitis. Fast progressive proptosis,
      oculomotor disorders, and pain are the most frequent alarm signals. After the
      diagnostic procedure, a surgical or medical treatment is frequently proposed.
      CONCLUSION: Although rare, emergencies in orbital diseases are a challenge for
      the general ophthalmologist. The morbidity and sometimes the mortality due to
      these diseases are often reduced by proper management. Patients generally have to
      be referred to a specialized unit.

PMID- 12515939
TI  - [A case of primary non-Hodgkin lymphoma of the lacrimal sac].
AB  - Malignant tumors of the lacrimal sac are uncommon, and primary non-Hodgkin
      lymphomas are rare. We report the case of an 80-year-old woman presenting with
      epiphora and swelling of the left lacrimal area. A dacryocystorhinostomy was
      programmed, but within few weeks a painful tumor appeared with cervical nodes.
      Pathological studies of the mass revealed diffuse malignant lymphoma with large B
      cells. The lymphoma was classified as stage IIE using Ann Arbor staging after
      clinical, biological and radiological examination. Six CHOP systemic chemotherapy
      were proposed. After 12 months and only 4 cures because of hematological
      complications and cardiac toxicity, the patient was disease-free. Primary non
      Hodgkin lymphoma of the lacrimal sac is extremely rare. Collaboration between the
      ophthalmologist, anatomopathologist and oncologist allowed us to determine the
      type and the extension and to propose an aggressive but successful treatment in
      this highly malignant and very localized lymphoma.

PMID- 12515940
TI  - [Correlation between changes in the nerve fiber layer and examination of the
      visual field using automatic perimetry in diagnosing primary open angle
      glaucoma].
AB  - PURPOSE: To analyse the correlation between changes in the nerve fiber layer and
      the appearance of defects in the visual field in primary open angle glaucoma
      (POAG). MATERIAL: and methods: Digital image processing of the nerve fiber layer
      and examination of the visual field (30-2 Humphrey) was performed in 450
      patients. The conditions for obtaining the digital images are presented. RESULTS:
      Defects of the nerve fiber layer were evaluated qualitatively and quantitatively
      using automatic perimetry and the correlation was estimated. The results are
      discussed. CONCLUSION: Examination of patients suspected of having POAG is much
      more precise when using both techniques performed the same day. Thus it will be
      possible to save time for: early diagnosis, monitoring the treatment, limiting
      the progression of glaucoma.

PMID- 12515941
TI  - [Cutaneous palpebral anthrax].
AB  - The interest for anthrax is permanent because of its difficult diagnosis, its
      severe prognosis, and the possibility of its dissemination during biological war
      and bioterrorism. Cutaneous anthrax is an infectious disease caused by Bacillus
      anthracis. Palpebral localizations are rare, raising problems of differential
      diagnosis. The case of a 21-year-old male with palpebral anthrax is presented.
      The diagnosis was established by the progression of the palpebral lesions
      (serohemorrhagic vesicle, black necrotic eschar), extended palpebral edema, and
      positive epidemiological data. During the onset period, the differential
      diagnosis was difficult because of uncharacteristic symptoms, negative
      bacteriological tests (previous antibiotic treatment), and the absence of
      epidemiological data. Treatment with G penicillin led to the patient's cure.

PMID- 12515942
TI  - [Bilateral retinitis: early manifestation of subacute sclerosing panencephalitis.
      A case report].
AB  - Subacute sclerosing panencephalitis (SSPE) is a progressive encephalitis caused
      by persistent measles infection. The disease is almost always fatal and mainly
      affects children and young adults. Ophthalmological signs are frequently observed
      and can be the presenting manifestations. We report the case of a 22-year-old
      young man who presented with bilateral posterior retinal necrosis confirmed by
      fluorescein angiography and normal laboratory tests. The appearance of peripheral
      retinal tears and stereotyped myoclonic movements were signs of the evolving
      condition. Diagnosis of SSPE was confirmed by brain MRI, EEG, and cerebrospinal
      fluid examination. The patient's neurological condition deteriorated rapidly and
      he died 2 months following the onset of ophthalmological manifestations.

PMID- 12515943
TI  - [Ocular impairment during type II membranoproliferative glomerulonephritis].
AB  - Membranoproliferative glomerulonephritis type II (MPGN) is characterized by dense
      deposits within glomerular basal membrane and Bruch's membrane which result in
      retinal lesions similar to drusens. We observed a 50-year-old patient with
      chronic renal deficiency who developed central bilateral serous retinopathy with
      diffuse punctiforme yellow subretinal lesions. Ophthalmoscopic and angiographic
      aspects led to an MPGN type II diagnosis. Specific posterior segment lesions are
      described during MPGN type II. Dense deposits concerned both lamina densa of
      glomerular basal membrane and Bruch's membrane with choriocapillaris. The main
      ocular complications were central serous chorioretinopathy and choroidal
      neovascularization. We review the clinical and evolutive aspects of this disease.

PMID- 12515945
TI  - [MRI used in the exploration of occulomotor muscles].
AB  - PURPOSE: To improve existing MRI (magnetic resonance imaging) methods of
      assessing ocular motility in horizontal gaze by using a multistatic fast imaging
      T2W MRI sequence, preventing patient head movement and convergence of the eyes
      during the study for diagnosis and management of complex paralytic strabismus.
      METHODS: A turbo-RARE image of the orbits was acquired in a set plane each time
      the patient fixed on a virtual image of 1 of 15 LEDs (light emitting diodes). The
      head was positioned and immobilized with a security cushion at an 8 degrees tilt
      of the 25-cm quadrature head coil. After completion of the study (5 mn), the MRI
      images were transferred to a work station and then onto a magnetic video tape to
      be replayed in cine mode on a PC using standard software. The qualitative
      analysis was completed by the study of quantitative parameters: visual axis,
      minor axis of the lens, the lines and angles of the horizontal rectus muscles
      with the optic nerve and the visual axis. We used digital image analysis to
      measure the cross-sectional areas of these muscles and also to determine muscle
      volume. Twenty normal volunteers and 3 cases of oculomotor palsies were studied.
      RESULTS: The experimental setup allowed us to obtain images which:1) CONCLUSION:
      This method will provide useful functional quantitative information in the
      evaluation of ocular motility disorders. The procedure is readily clinically
      applicable.

PMID- 12515946
TI  - [Cyclotorsions].
AB  - Cyclotorsions are movements of cyclorotation of the eyes (in- or ex-cycloversions
      or vergences) and positions of cyclotorsion (in- or ex-cyclotorsion or
      cyclodeviation). Torsion is absent when the vertical meridian 0 traversing the
      cornea center is parallel to a plumbline. In a state of intorsion, the nasal end
      of the horizontal meridian is higher than the temporal part: the optic disk is
      lower than the fovea. Conversely the optic disk is higher in cases of
      excyclotorsion. Fundus observation is the only objective test in cases of
      torsion. Cyclodeviations are peripheral in nature (ex: SO palsy orbital
      strabismus) or linked to fixation (ex: congenital nystagmus, incyclo, and DTDs in
      infantile strabismus). All the facias and the orbits play a role in
      cyclorotations. The anterior fibers of the oblique muscles are responsible for
      torsion. Dissociated surgery and shift of the insertion follow. In a situation of
      cyclotorsion, the recti act differently (Weiss): the medial rectus becomes an
      elevator and is less an adducto, the superior rectus is less an elevator, etc.
      The consequences are alphabetic deviations, tilt of the coordimeter and
      synoptometer charts, displacement surgery of the recti insertions. Surgery of the
      facias must not be ignored. The study of torsions is currently evoluing.

PMID- 12515947
TI  - [The function of Tenon's capsule revisited].
AB  - Tenon's capsule is at the forefront of today's strabismus news. Its function as a
      muscle pulley was recognized by Tenon himself in 1806. Neiger, then Koornneef,
      and more recently Demer gave a more modern description of Tenon's capsule. The
      anterior or muscular part is made up of collagen, elastic, and smooth muscle
      fibers. It forms a sleeve around extraocular muscles from the Tenon foramen to
      their scleral insertion. Directly in front of the foramen, it includes a zone of
      strong capsular-muscular adherence, which is also solidly suspended by ocular
      suspension system to the periosteum of the orbit; the intermuscular membrane
      consolidates the adherence zones of the rectus muscles. The posterior part is
      simply a condensation of collagenous fibers. The function of Tenon's capsule is
      essential. At the place where it adheres to the muscles, the sleeve that it forms
      around the muscles plays the role of a pulley diverting the muscle's path, with
      the pulley representing the proximal functional insertion of the muscle. The
      position of a rectus muscle's pulley is stable during ocular movements
      perpendicular to the axis of this muscle because of the transversal and radial
      fastening of the capsular-muscular adherence zone. During movements along the
      muscle axis, the pulley moves with the ocular globe. In fact, it is positioned
      actively to accompany the ocular globe's movements. The anomalies of these
      pulleys can contribute to or be responsible for an extraocular muscle imbalance:
      a position anomaly, an instability, a displacement, or a pathological adherence
      of one pulley can be the cause. Surgery of Tenon's pulley has always been an
      integral part of extraocular muscle surgery. Any intervention on the muscular
      level involves, to a lesser or greater extent, the operated muscle's pulley.
      Different examples demonstrate this.

PMID- 12515949
TI  - [Neovascular glaucoma].

PMID- 12515950
TI  - [Inflammation of an ectopic pinguecula].
AB  - An 80-year-old male patient experienced recently diagnosed swelling of the limbal
      conjunctiva. In his clinical history were found cataract surgery on the right eye
      3 months before, chronic open angle glaucoma effectively treated by local eye
      drops, treated systemic hypertension and hypercholesterolemia. On ophthalmic
      examination, a conjunctival mass was present in the inferior lateral conjunctival
      quadrant next to the limbus, with numerous vessels visible at its top. Treatment
      with topical corticosteroids failed to obtain regression, but decreased the local
      inflammatory signs. The persistence of the mass led to its surgical excision
      under local anesthesia. Histopathology found a subepithelial accumulation of
      modified collagen bundles typical of elastotic degeneration. Capillary vessels
      were seen in the superficial subepithelial area, attesting to the high degree of
      vascularization observed clinically. The final diagnosis was a pinguecula, which
      was not exactly located on the horizontal meridian area as it is usual.

PMID- 12515951
TI  - Smallpox vaccine.

PMID- 12515952
TI  - OTC loratadine.

PMID- 12515953
TI  - [Development of Micro CT and it's usefulness for structural analysis of pulmonary
      disease].

PMID- 12515954
TI  - [Some advice about English summary in a paper: for beginners].

PMID- 12515955
TI  - [Effect of relaxation time in flair magnetic resonance imaging].

PMID- 12515956
TI  - [Apparatus engineering of X-ray CT equipment (6): newest CT technology].

PMID- 12515957
TI  - [The 87th scientific assembly and annual meeting of the Radiological Society of
      North America].

PMID- 12515958
TI  - [Objection to "Clinical professor"].

PMID- 12515959
TI  - [Under diagnostic X-ray surveilance area, leakage radiation measurement manual
      part 1].

PMID- 12515960
TI  - [Evaluation of scatter rejection system using a metal filter].
AB  - Grids are used for the purpose of reducing scattered radiation. In portable
      radiography, however, accurate positioning of the grid is difficult. Errors in
      alignment may cut off the primary beam, which can result in misdiagnosis. We
      devised a metal filter with scatter rejection properties and evaluated its
      performance. The filter, which has no intrinsic alignment mechanism, is placed in
      front of the IP. We evaluated aluminum (Al), copper (Cu), and tantalum (Ta)
      filters by comparing them with low-ratio grids of 3:1 and 5:1. In the total
      evaluation, Ta (0.03mm) demonstrated high visualization of light and minute
      vascular shadow and visceral pleura, and the Bucky factor was lower than that of
      the 3:1 grid, while the clinical target was very clear. Because of its high
      atomic number, Ta can absorb a low energy component effectively even if it is
      very thin. Because of the K absorption edge, Ta also decreases the high-energy
      components that cause photographic contrast to decline. Therefore, Ta proved to
      be a highly suitable material for this research. An air gap within 4cm was not
      effective for the purpose of supporting the reduction in scattered radiation of
      the metal filter. The method of placing a metal filter in contact with the
      patient is more practical and makes the system very thin. This system is thought
      to be effective for portable radiography because it is light, easy to use, and
      flexible in structure and does not cause misalignment.

PMID- 12515961
TI  - [Absorption and scatter with an acrylic plate attached to the front of an X-ray
      beam limiting device].
AB  - We measured X-ray absorption and scatter with an acrylic plate attached to the
      front of the X-ray beam limiting device. The acrylic plate played the role of an
      added filter, absorbing the low energy element of the X-ray beam and decreasing
      the surface dose to 4.3% of the extreme height as a result. However, the surface
      dose outside the irradiation field increased to 35.3% of the extreme height, and
      the scatter dose increased to 47.8% of the extreme height. An acrylic plate with
      the minimum thickness necessary should be used to decrease unnecessary exposure
      outside the irradiation field.

PMID- 12515962
TI  - [Lateral radiography of the knee with single-leg standing].
AB  - The purpose of this investigation was to accomplish reproducible radiography of
      single-leg standing lateral radiography of the knee by adjusting lateral rotation
      using a ruler to measure foot position. After preliminary assessment of three
      dimensional CT of the knees of normal volunteers, the best adjustment of external
      rotation was estimated. A ruler was made for use in adjusting the angle of knee
      rotation by measuring foot rotation. Based on the foot rotation measured by this
      ruler, the positioning of radiography was adjusted to correct rotation. Rotation
      was estimated by the distance between the posterior edges of the lateral and
      medial femoral condyles. Fifteen-degree and 17.5-degree rotations were used for
      correction. Correction of rotation was 17 degrees on average. This helped not
      only to correct external rotation in the initial radiography but also to correct
      rotation for repeat radiography. Our method is quantitative and highly
      reproducible, and it increases the success rate of lateral knee radiography.

PMID- 12515963
TI  - [Influence of electromagnetic waves on portable electronic instruments in
      medicine].
AB  - In this work, we considered the effect of electromagnetic compatibility (EMC) on
      electronic instruments used in medical facilities. We simulated and measured the
      intensity distribution of the electromagnetic field around portable phones and
      examined the influence of electromagnetic field on telemeter-type
      electrocardiograms (ECG) and computer display cathode ray tubes (CRT) when
      portable phones were brought close to them. Results showed that the waves
      observed on ECG are affected up to a distance of 55cm (3.55E+03V/m) from the
      portable phone, and the grid of the computer display is affected up to a distance
      of 9cm (7.16E+04V/m) in the front and 14cm (2.97E+04V/m) in the back. Therefore,
      to reduce electromagnetic intensity (EMI) maintaining a distance far enough from
      the source is effective.

PMID- 12515964
TI  - [Trial manufacture of subsidiary tool and use of technique for shoulder joint of
      "Scapula Y"].
AB  - The technique of "Scapula Y " is effective for capturing forward/backward
      dislocation of the humeral head and variation in surgical spine fracture. It is
      also indispensable for describing images of ossification at the tendon plate of
      the lower lobe of the acrominon and impingement syndrome. However, owing to large
      individual variations in body shape and position and shape of the scapula, the
      conventional method does not lend itself to stable reproduction of position or
      provide adequate diagnostic information. We measured the central angle of entry
      from scapula m24 pairs of dried bone (Indian) into the spine of the scapula from
      horizontal and forehead planes to determine the range of variation together with
      the clinical data referred to in the next paragraph. We then manufactured a trial
      subsidiary tool to set the angle of the central entering beam base on the
      acrominon to the spine of the scapula using data on measured angle from 50
      clinical radiographs. We identified improvement in radiography of the scapula by
      using the subsidiary tool designed and manufactured on the basis of the above
      measured data.

PMID- 12515965
TI  - [Method of injection of contrast medium for brain perfusion CT].
AB  - Perfusion computed tomography (CT) has great value for detecting stroke and
      evaluating blood flow in the brain. With perfusion CT, it is possible to obtain
      two absolute values, cerebral blood flow (CBF) (ml/min/100g) and cerebral blood
      volume (CBV) (%). In using this examination, the main problem is the method of
      iodine injection. The maximum slope of time-attenuation curve in organs must be
      reached before the peak enhancement time of the sagittal sinus. To solve this
      problem, we used a new method in which total injection volume is 30ml, and the
      rate of injection is 9ml/sec. The data acquisition time is one second for each
      scan, and the time interval is one second, for 20 scans in total. With this
      method, we can obtain reliable information on blood flow in the damaged brain.
      The most common examination used for the detection of brain blood flow is single
      phased dynamic CT with Xe inhalation. However, the Xe inhalant examination is
      difficult to use in the routine clinical setting. Perfusion CT will be more
      useful for the detection of brain blood flow.

PMID- 12515966
TI  - [Educational programs and self-management in bronchial asthma].
AB  - Bronchial asthma is one of the most common chronic diseases in the world and can
      affect people of all ages. In the last few years there has been a considerable
      improvement in the etiopathogenetic knowledge of the disease and extremely
      effective anti-asthmatic drugs are available. However, asthma-related morbidity
      and mortality are increased, especially in Western countries. In an attempt to
      reverse this negative trend, for a number of years national and international
      guidelines on asthma have been published all over the world. These guidelines
      have the aim of improving asthma diagnosis and treatment and of conveying a
      fundamental educational message both to health workers and to patients and their
      families. From the data in the literature it can be clearly seen that only
      through the application of valid educational programs is it possible for
      asthmatics to improve their knowledge of the disease and to understand how they
      can look after themselves by a careful evaluation of their own symptoms and
      respiratory function. They should also be aware of the drugs available for the
      treatment of both acute asthmatic crises and chronic asthma, but especially of
      the fact that this chronic inflammatory affection can be fully treated. In
      particular, an educational program organized with groups of maximum 10-12 people
      attending 2 lessons and with helpful training tools, can increase significantly
      asthma knowledge, treatment compliance and patient self-management. The aim of
      this review is to highlight the importance of educational programs and those
      obscure areas which slow down their large scale application and universal
      acceptance.

PMID- 12515967
TI  - [Whipple's disease: progress in the diagnosis and review of the literature].
AB  - Whipple's disease is a rare, chronic, multisystemic disease characterized by the
      presence of fever, diarrhea, weight loss and malabsorption, preceded by
      arthritis. Although Whipple's disease almost always includes involvement of the
      small intestine and the presence of malabsorption, it commonly affects other
      organs, especially the heart, brain, eyes and joints. Whipple's disease greately
      mimics other diseases and is caused by a cultivation-resistant bacterium. The
      disease is fatal unless patients are treated with antibiotics. The diagnosis of
      Whipple's disease can be made by histologic analysis of small-intestinal biopsy
      specimens. Identification of Whipple bacterium, Tropheryma whippelii, has led to
      the development of the polymerase chain reaction This technique can be used to
      detect the bacterium in many organs and fluids, including synovial tissue and
      fluid. Affected patients tend to have dilated intestinal villi that are
      infiltrated with foamy macrophages.

PMID- 12515968
TI  - [Mondor's diseases. Spectrum of the clinical and pathological features].
AB  - Mondor's disease is an uncommon disorders, occurring mostly in middle-aged women,
      and characterized by superficial thrombophlebitis classically involving the
      thoraco-epigastric veins and/or their confluents. Rare cases have been reported
      in atypical sites (upper arms, abdomen, groin and penis). The most common
      clinical features include lateral chest wall tension and pain, as well as the
      presence of a tender subcutaneous linear or winding cord-like structure,
      corresponding to the affected vessel, often with skin redness, edema or
      retraction. The etiology is unknown. Mondor's disease may be primary or secondary
      to local trauma, surgical procedures, bandaging, tight clothes and infections; it
      may also be associated with breast cancer. This condition is usually a benign and
      self-limited process, requiring only symptomatic treatment. Surgery is indicated
      when it is associated with malignancies or severe local pain and retraction. The
      clinical and pathological spectrum of this disease are reviewed.

PMID- 12515969
TI  - [Possible animal models of endocrine, immune and reproductive complications of
      celiac disease].
AB  - This paper underlines the need of developing animal models to study the diverse
      complications of celiac disease (CD). CD is a multifactorial condition requiring
      both an exogenous element (gluten) and complex genetic factors; moreover, CD is
      associated to several endocrine, immune and reproductive diseases, whose onset
      may be influenced by other environmental factors as well. In particular, the
      intestinal absorption of exogenous factors may be important for the outcome of CD
      as well as of the associated diabetes and/or thyroiditis. Presently, there are no
      adequate animal models for the systemic complications of CD; in particular, there
      are no gene knock-out models. However, models are available as regards either
      gluten enteropathy, such as Irish Setter and Balb/c e BDF1 mouse strains, and
      endocrine-immune diseases associated with CD, such as BB rats and NOD mice. A
      deeper exploitation of the available models could provide important information
      on the factors modulating intestinal permeability, the pathogenesis of
      extraintestinal alterations and the interactions between gluten and other
      metabolic, nutritional and environmental factors. The elaboration of in vivo
      models requires a sound basis of knowledge at molecular level, as well as the
      modulation of the metabolic alteration through relevant exogenous factors, first
      of all the dietary assumption of gluten. Therefore, the availability of
      experimental models may provide significant advances on the prevention and
      treatment, allowing a complete analysis of affected organisms as well as the use
      of pharmacological and/or immune stimuli; more information may be also derived on
      the possible long-term effects of gluten traces in CD-affected subjects, thus
      reducing the need for lengthy clinical studies.

PMID- 12515970
TI  - [Effects of the combined raloxifene-sodium fluoride therapy on bone mass and bone
      turnover in women with postmenopausal osteoporosis].
AB  - BACKGROUND: Aim of the study was to compare the effects of raloxifene (RLX)
      therapy alone or with a combination of RLX and slow release sodium fluoride
      (SRNaF) on bone mineral density (BMD) and bone turnover, at 1 year. METHODS:
      Ninety-two consecutive postmenopausal women with osteoporosis (49-62 yr old) were
      randomly allocated to a group A (n=48; RLX 60 mg/day per os) or a group B (n=44;
      RLX 60 mg/day per os plus SRNaF 25 mg x 2/day per os); all participants received
      oral calcium carbonate (500 mg x 2/day) and vitamin D3 (400 UI x 2/day) too.
      Lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray
      absorptiometry (DEXA) at time 0 (T0), after 6 (T6) and 12 (T12) months; at the
      same time, serum bone specific alkaline phosphatase (BALP) and urinary N-terminal
      telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined
      at T0, T6 and T12. RESULTS: Eighty-five women completed the study, 45 in group A
      and 40 in group B. In group B, after 1 year of treatment, we found a significant
      (p<0.01) increase in L1-L4 BMD (3.9+/-0.3%) respect to group A (2.8+/-0.1%); FN
      BMD in group B increased by 3.3+/-0.3% which was significantly different (p<0.01)
      from group A (2.3+/-0.1%), at 1 year. After 12 months of therapy, NTx/cr
      decreased significantly more (p<0.05) in group B (-36+/-2.6%) than group A (-29+/
      2.0%); BALP levels increased in group B and decreased in group A: in group B BALP
      levels (11+/-1.2%) significantly increased (p<0.001) than group A (-2.1+/-0.1%),
      since 6th month. CONCLUSIONS: These data demonstrate that the combination of
      antiresorptive and bone-stimulating agents may dissociate bone resorption and
      bone formation and thus, by synergestic effect, induce a significative increase
      in BMD.

PMID- 12515971
TI  - Immunocytochemical profile of malignant pleural effusions of small-cell lung
      cancer.
AB  - BACKGROUND: Small-cell lung carcinoma (SCLC) is a highly malignant tumour of a
      somewhat distinctive cell type. The aim of this study was to determine the
      immunocytochemical profile of tumor cells and lymphoid cell in SCLC pleural
      fluids. METHODS: Nine cases of malignant pleural fluids of SCLC were studied
      using cell block preparation. In pleural effusions cytologically proven to be
      malignant in 9 patients with SCLC, the immunocytological features of tumor cells,
      together with the determination of lymphocytic subsets were documented. RESULTS:
      In all 9 cases, tumor cells reacted with neuron-specific enolase (NSE) (100%),
      whereas in 6 of 9 cases (66,66%) tumor cell expressed synaptophysin, thyroid
      transciption factor-1 (TTF-1) and chromogranin A antigens. Phenotyping of the
      lymphocytes revealed in the majority of cases an expression of CD3 and CD4
      antigens (8 and 7 cases, respectively) in contrast to CD8 and CD20 expression (1
      and 1 case, respectively). CONCLUSIONS: The reactivity pattern of the tumor cells
      with the markers used in our study is a specific for SCLC. No significant
      difference in the distribution of lymphocytic subpopulations is observed in
      correlation with other malignant and no malignant processes involving the pleural
      cavity.

PMID- 12515972
TI  - [The usefulness of the quantitative ultrasound to diagnose glucocorticoids
      induced osteoporosis].
AB  - BACKGROUND: The aim of this study was to evaluate the utilization of heel
      ultrasonometry in the diagnosis of glucocorticoid induced osteoporosis. METHODS:
      The study group included 108 caucasian women, ranging in age from 30 to 81 years.
      They were all affected by inflammatory disorders (rheumatoid arthritis and other
      connective tissue diseases) and had been in chronic glucocorticoid therapy for at
      least 8 months, at an average daily dosage of not less than 7.5 mg of
      prednisolone. The control group was composed of 112 women. Every subject was
      evaluated by a heel ultrasonography (Hologic Sahara). RESULTS: The ultrasonometry
      data average values noted were: QUI (Quantitative Ultrasound Index) 71* (86); SOS
      (Speed of Sound) 1324 m/sec* (1541); BUA (Broadband Ultrasound Attenuation) 61
      dB/MHz (62). The asterisk shows a statistically significant difference in
      comparison to the value in brackets. QUI/Stiffness and SOS had reached a
      significant statistic value in all the age groups, with regard to average values
      of patients not on glucocorticoid therapy. The BUA values did not demonstrate a
      significant difference, even if they always appeared inferior to the average
      observed (except in the range 60-70 years age group). CONCLUSIONS: The concept
      that osteoporosis is a disease characterized exclusively to a reduction in bone
      density, now leaves room for consideration that corresponds with the concepts of
      quantitative and quality elements. Chronic glucocorticoid therapy is one of the
      major causes of osteoporosis. The use of glucocorticoids increases the risk of
      fractures, independently from the bone uineral BMD in the various ages, which
      therefore cannot be explained solely by the reduced BMD. Ultrasound may provide
      information on the bone structure, and so its eventual modification, after
      chronic glucocorticoid therapy. Our results show that bone ultrasonometry is able
      to detect a population in chronic glucocorticoid therapy in comparison with those
      not treated. BUA and SOS are reduced in all the patients. Our experience derives
      that in the chronic glucocorticoid therapy patients, a major prevalence is noted
      of SOS which may provide information on the modification of the bone structure.

PMID- 12515974
TI  - Out of a recent CVI consensus: some features of a basic statement.
AB  - In March 1997 at the Abbaye des Vaux de Cernay, France, a multidisciplinary
      meeting of venous specialists, to do guidelines on venous management was held.
      Subsequently the faculty members revised the document and a consensus statement
      was published in Circulation, in November 2000, based on wide-ranging and
      authoritative research into the investigation of chronic venous insufficiency
      (CVI). The statement gives information on the epidemiology and pathophysiology of
      CVI including the changes in the major veins as well as in the microcirculation
      and the associated hematological changes. It sets out the methods used for
      morphologic and hemodynamic investigations into venous disease and for the study
      of the microcirculation stating their usefulness and limitations, and indicating
      their place in clinical practice and research. A section deals also with the rare
      venous malformations. It concludes with an application of the methods in the
      investigation on CVI based on the CEAP classification that gives a uniform way of
      reporting venous disorders. The document is intended both for the clinician and
      the researcher. A shortened version appears below.

PMID- 12515975
TI  - Pharmaco-epidemiology of the treatment of chronic venous insufficiency in general
      medicine.
AB  - BACKGROUND: A report is presented of a multicenter pharmaco-epidemiological study
      on chronic venous insufficiency conducted in France on 5043 patients. METHODS: It
      was based on a questionnaire that included the demographic characteristics of the
      patients, their risk factors for venous disease, history of venous insufficiency,
      physical and functional symptoms, and clinical stage according to the CEAP
      classification, as well as modalities of treatment and professional practice of
      the participating doctors. The various treatment modalities (phlebotonics,
      compression stockings, sclerotherapy and surgery) were related to the stage of
      the venous insufficiency and to the satisfaction expressed by the patients.
      RESULTS: The results of the study showed a minimum annual sick leave rate of
      7.2%. CONCLUSIONS: In conclusion, this study brings to the fore the change in
      treatment modalities for venous insufficiency according to its severity stage,
      principally as regards medico-economics.

PMID- 12515976
TI  - Role of the endothelium and blood stasis in the development of varicose veins.
AB  - Today, chronic venous insufficiency affects millions of people but the
      investigation of veins and of venous diseases is still very poor. Additionally,
      the mechanism of the occurrence of varicose veins is not understood. Blood stasis
      is often associated with these pathological situations and we propose that
      resulting ischemic conditions can trigger the endothelium to release inflammatory
      mediators and growth factors. On one hand, the inflammatory mediators will
      recruit and activate neutrophils, which then infiltrate the venous wall and
      damage components of the extracellular matrix. On the other hand, growth factors
      induce smooth muscle cell migration, proliferation and de-differentiation into
      the synthetic phenotype, all together leading to the formation of neointima.
      These processes, being repeated over time, would eventually lead to alterations
      of the venous wall as observed in varicose veins. Venotropic drugs are used to
      treat chronic venous insufficiency. They are able to increase venous tone and to
      decrease vein and capillary permeability but they are also able to protect the
      endothelial cells against ischemia. Indeed, they target complexes of the
      mitochondrial respiratory chain and maintain ATP production during hypoxia.
      Hence, the cells are resistant to ischemia and do not release inflammatory
      mediators and growth factors. These drugs should thus be able to prevent the
      alterations of the venous wall induced by blood stasis.

PMID- 12515977
TI  - Deleterious effects of white cells in the course of skin damage in CVI.
AB  - Venous ulceration remains a common problem and a significant challenge to the
      physicians treating it. Many theories have been advanced in the past to explain
      its causes but there is little evidence to support tissue hypoxia as the main
      factor, as was once thought. In recent years attention has focussed on the
      inflammatory events which attend venous disease and the development of venous
      ulceration. It has been proposed that these form a major contribution to the
      development of venous leg ulcers. In the arterial system an analogous series of
      events appears to cause damage following severe ischemia. Massive neutrophil
      activation in the microcirculation following reperfusion of a tissue results in
      severe, ischemic damage to that tissue. A similar series of events is proposed to
      explain venous disease. During venous hypertension leukocytes are sequestrated in
      the microcirculation of the lower limb. It has been shown that these undergo
      activation whilst they are in the leg. The exact location of leukocyte
      sequestration is unclear but it is suggested that this may occur in the skin. The
      damage caused to the lower limb skin components can be identified by measuring
      plasma levels of endothelial adhesion molecules, which are shed into the
      circulation following a period of venous hypertension. In the long term this
      leads to a chronic inflammatory state in the skin in some patients where venous
      hypertension is sustained or there is susceptibility to venous hypertension. The
      resulting inflammatory process is referred to as "lipodermatosclerosis" and has a
      number of well known clinical features. There is proliferation of the dermal
      capillaries eventually leading to a "glomerulus" like appearance. In the skin and
      subcutaneous tissues there is fibrosis. The microcirculation in the papillary
      dermis is surrounded by an inflammatory cellular infiltrate. The importance of
      understanding the mechanisms of the development of venous ulceration is in
      creating new treatments for this problem. Compression treatment has been
      effective in healing leg ulcers for thousands of years. Surgical treatment offers
      a possible cure in patients where superficial venous reflux is the main problem.
      Deep vein reconstruction is only suitable for a few patients. Many venous ulcers
      can be healed by compression, only to recur within a few months. Pharmacological
      treatments may offer the possibility of more rapid ulcer healing and the
      maintenance of an ulcer-free state if the correct pathophysiological mechanisms
      can be identified and addressed.

PMID- 12515978
TI  - Pharmacological targets of drugs employed in chronic venous and lymphatic
      insufficiency.
AB  - Numerous compounds acting on the venous system have been developed over the last
      50 years, including and often associating flavonoids, pycnogenols, saponosides,
      nucleosides and bilobatides. Some products have proved highly successful such as
      Cyclo 3 Fort (Fabroven), Phlebodril, made of ruscus extract (flavonoids,
      saponins), hesperidin-methyl-chalone and ascorbic acid. This presentation is an
      attempt to classify the scientifically proven mechanisms of such substances. All
      selected substances have been tested in clinical trials for their action on the
      symptoms of chronic venous insufficiency (CVI), leg pain and edema. As the
      distensibility of the leg veins is the main pathological factor determined by
      plethysmogaphy, it was at first thought that leg pain would be related to it. But
      observations have shown that this factor is often unrelated to the enlargement of
      the veins but rather to a whole chain of factors. The effects of different drugs
      on venous distensibility, rheological disorders, the prevention of wall dystrophy
      and action on the microcirculation are examined.

PMID- 12515979
TI  - Sclerotherapy of varicose leg veins. Technique, indications and complications.
AB  - The aim of treatment by sclerotherapy is the fibrous occlusion of varicose veins
      and the absence of recanalization of an intravascular thrombus. Modern
      sclerotherapy started at the beginning of the 20(th) century in Europe. Tournay
      in France, Sigg in Switzerland and Fegan in Ireland developed different schools
      of practice. Recently ultrasound-guided sclerotherapy has appeared, mainly for
      the treatment of saphenous trunks and incompetent perforating veins. The precise
      diagnosis of varicose vein disease and the recognition of the most proximal point
      of reflux dictates the choice of optimal treatment and reduces the risk of
      recurrence and complications such as pigmentation or matting. The risk of
      complications depends on the agent used, its concentration and the quantity
      injected. Sclerotherapy is the treatment of choice for spider veins and is
      indicated in the treatment of reticular and short saphenous varicose veins. There
      is currently no consensus on the place of sclerotherapy in the treatment of the
      long saphenous vein and incompetent perforating veins. Neither is there a
      consensus on the type and duration of the compression to be applied after
      sclerotherapy. Sclerotherapy is safe and in the hands of experts the risk and
      secondary side effects of the treatment are minimal.

PMID- 12515980
TI  - Phlebectomy. Technique, indications and complications.
AB  - Phlebectomy, first described by Aulus Cornelius Celsus (25 BC - 45 AD), was re
      invented 40 years ago by Dr. Robert Muller, in Neuchatel, Switzerland. This safe,
      esthetic, effective and economical operative technique has now been fully
      developed and adopted all over the world. Phlebectomy hooks enable venous
      extraction through minimal skin incisions (1-3 mm) or even needle punctures,
      assuring complete and definite eradication of the veins. The small size of the
      skin incisions usually results in little or no scarring, contrary to that found
      in classical venous surgery, and avoids the possible complications of
      sclerotherapy, such as skin necrosis or residual hyperpigmentation. Sites
      particularly appropriate for ambulatory phlebectomy include incompetent saphenous
      veins (except the sapheno-femoral and in most cases the sapheno-popliteal
      junctions), their major tributaries, perforating, groin pudendal veins, reticular
      veins (popliteal fold, lateral thigh and leg) and veins of the ankles and the
      dorsal venous network of the foot. Curettage of telangiectasias is a less well
      known indication, but it is also quite effective in removing networks of thick
      blue spider veins. Ambulatory phlebectomy of body areas, other than the legs,
      include dilated periorbital, temporal or frontal venous networks and venous
      dilatation of the abdomen, arms or dorsum of the hands. Long term results, if the
      indications and technique were correct, are excellent. Complications, in skillful
      hands, seldom occur. They may be classified as cutaneous, vascular, neurological
      or general and are usually benign.

PMID- 12515981
TI  - Point and click.

PMID- 12515982
TI  - Palliative and end-of-life care: policy analysis.
AB  - PURPOSE/OBJECTIVES: To present an overview of policy issues affecting hospice and
      palliative care focusing on the nursing home and hospital settings and to discuss
      factors affecting end-of-life care, policy initiatives, recent legislation, and
      nursing implications. DATA SOURCES: Published articles; technical, advisory, and
      research reports (from government, professional, and private organizations);
      newsletters; textbooks; meeting minutes; online references; and legislative
      documents. DATA SYNTHESIS: Improvements are needed in end-of-life care,
      especially with regard to access, delivery, and financing of such services.
      Legal, organizational, and reimbursement policies, as well as healthcare
      professional education, have been identified as areas that need improvement. The
      nursing shortage and variable reimbursement policies for nursing services have a
      significant impact on access to quality end-of-life care, especially for
      underserved populations. CONCLUSIONS: A need exists for further research,
      including demonstration projects to test new ways to deliver and integrate
      hospice and palliative care throughout the illness continuum. Education and
      research are needed regarding symptom management, communication and decision
      making, caregiver support, and other end-of-life issues. Nursing interventions,
      palliative care networks, and other models that promote a coordinated approach to
      care delivery have been shown to decrease costs and improve quality of care.
      IMPLICATIONS FOR NURSING: Nurses play a key role in advancing improvements in
      palliative and end-of-life care through their involvement in educational, quality
      improvement, research, and legislative initiatives. Nursing activities in these
      areas may contribute to improved access, lower costs, and improved quality of
      care in advanced illness.

PMID- 12515983
TI  - The role of licensed nursing personnel in radiation oncology part a: results of a
      descriptive study.
AB  - PURPOSE/OBJECTIVES: To identify the specific administrative, clerical, patient
      care, patient education, and research responsibilities that licensed nursing
      personnel perform in the field of radiation oncology. DESIGN: Descriptive.
      SAMPLE: 281 licensed nursing personnel employed in the field of radiation
      oncology in North America. METHODS: Subjects completed a six-page, self
      administered questionnaire comprised of fixed-choice and open-ended questions.
      MAIN RESEARCH VARIABLES: Demographics, employment settings, and administrative,
      clerical, patient care, patient education, and research responsibilities.
      FINDINGS: Nurses in radiation oncology tend to be older (41-60 years of age) and
      considerably well educated, with many years of experience in this field. Nurses
      are responsible for a wide variety of tasks. The study found a strong
      demonstration of the role of nurse educator among radiation oncology nurses.
      IMPLICATIONS FOR NURSING: Radiation oncology nursing is a subspecialty in
      evolution. The data should provide support for further exploration of how patient
      education and support influence patient outcomes in radiation oncology.

PMID- 12515984
TI  - The role of licensed nursing personnel in radiation oncology part B: integrating
      the ambulatory care nursing conceptual framework.
AB  - PURPOSE/OBJECTIVES: To describe the professional opportunities for licensed
      nursing personnel in radiation oncology within the conceptual framework developed
      for ambulatory care nurses by the American Academy of Ambulatory Care Nursing
      (AAACN). DATA SOURCES: Published articles and books. DATA SYNTHESIS: Using
      AAACN's framework, the researchers identified three roles that are part of every
      ambulatory care nurse's practice and can be readily customized to radiation
      oncology: an organizational/systems role, a professional role, and a clinical
      nursing role. Incorporating the described framework into a radiation oncology
      nurse's job description can lead to maximizing the use of the professional staff
      member within the radiation oncology department. This level of professional
      utilization and validation of the radiation oncology nurse will lead not only to
      improved patient outcomes but also to greater professional satisfaction,
      resulting in improved retention. CONCLUSIONS: The complexity of oncology
      therapies demands expert oncology nurses. This clearly is recognized in medical
      oncology, and patients with cancer who are being treated with radiation are no
      less important. To optimize patient care and therapeutic outcomes, the
      integration of nursing in all aspects of the radiation treatment continuum is
      essential. IMPLICATIONS FOR NURSING: Radiation oncology nursing is an evolving
      subspecialty. Nurses can use the information in this article to evaluate their
      current roles and individual potential for further professional growth.

PMID- 12515985
TI  - The PRO-SELF(c): Pain Control Program--an effective approach for cancer pain
      management.
AB  - PURPOSE/OBJECTIVES: To describe the PRO-SELF(c): Pain Control Program, an
      educational approach that provides patients and family caregivers with the
      knowledge, skills, and nursing support needed to improve pain relief. DATA
      SOURCES: Published research studies, articles, and conference abstracts. DATA
      SYNTHESIS: Patients with cancer and family caregivers lack knowledge about pain
      management and side effects. Engaging in self-care behaviors improves patients'
      health outcomes. CONCLUSIONS: The PRO-SELF: Pain Control Program is an effective
      approach that can be used to help patients with cancer and their family
      caregivers obtain the knowledge and skills that are needed to manage pain. Three
      key strategies for delivering the PRO-SELF program are (a) provision of
      information using academic detailing, (b) skill building with ongoing nurse
      coaching, and (c) interactive nursing support. IMPLICATIONS FOR NURSING: Adequate
      pain relief is vital to decreasing cancer morbidity and improving patients'
      quality of life. The PRO-SELF: Pain Control Program should be implemented in all
      settings where cancer care takes place.

PMID- 12515986
TI  - Meta-analysis of the effect of psychoeducational interventions on pain in adults
      with cancer.
AB  - PURPOSE/OBJECTIVES: To determine the effect of psychoeducational interventions on
      pain in adults with cancer. DATA SOURCES: 25 intervention studies published from
      1978-2001. DATA SYNTHESIS: When analyzed across all studies, a statistically
      significant, beneficial effect on pain was found. However, threats to validity
      were present in some studies. The most serious of these involved a lack of random
      assignment to treatment condition and a floor effect on pain. When limited to the
      studies with the best methodologic quality, the effect on pain continued to be
      statistically significant. Effect on pain by type of treatment was examined and
      found to be somewhat variable and limited by the small number of studies testing
      each type of treatment. CONCLUSIONS: Methodologic quality was variable.
      Reasonably strong evidence exists for relaxation-based cognitive-behavioral
      interventions, education about analgesic usage, and supportive counseling.
      Minimal data were available about the relative effectiveness of different types
      of psychoeducational interventions because few studies included within-study
      contrasts of different experimental interventions and usual care was not well
      documented. IMPLICATIONS FOR NURSING: Psychoeducational interventions are not a
      substitute for analgesics, but they may serve as adjuvant therapy. Assessment and
      clinical judgment are critical. The intervention must be acceptable to patients
      and not too burdensome for patients in pain to use.

PMID- 12515987
TI  - Improving the quality of decision making in breast cancer: consultation planning
      template and consultation recording template.
AB  - PURPOSE/OBJECTIVES: To describe two templates that can be used to improve the
      quality of breast cancer treatment decisions. DATA SOURCES: Case study, survey of
      current users, three clinical trials. FINDINGS: Clinical applications of the
      Consultation Planning Template and Consultation Recording Template vary across
      organizations. Clinical trials have demonstrated that the templates can improve
      the quality of decisions, the quality of communication between patients and
      providers, and satisfaction. CONCLUSIONS: The templates can be adapted to
      different clinical settings and can improve the quality of treatment decisions.
      IMPLICATIONS FOR NURSING: Nurses often provide the majority of education and
      coaching for patients making decisions. As patients' demands for involvement in
      decision making increase, nurses need practical tools to help patients
      participate. The templates are practical tools that nurses can use to help
      patients make better decisions.

PMID- 12515988
TI  - Provision of individualized information to men and their partners to facilitate
      treatment decision making in prostate cancer.
AB  - PURPOSE/OBJECTIVES: To determine if providing individualized information to men
      who are newly diagnosed with prostate cancer and their partners would lower their
      levels of psychological distress and enable them to become more active
      participants in treatment decision making. DESIGN: Quasiexperimental, one group,
      pretest/post-test. SETTING: The Prostate Centre at Vancouver General Hospital in
      British Columbia, Canada. SAMPLE: Convenience sample of 74 couples. 73 men had
      early-stage prostate cancer. Mean age of the men was 62.2 years, and mean age of
      the partners was 58.1 years. The majority (> 50%) had received their high school
      diplomas. METHODS: Respondents completed measures of decision preferences and
      psychological distress at the time of diagnosis and four months later. All
      participants used a computer to identify their information and decision
      preferences. Computer-generated, graphic printouts were used to guide the
      information counseling session. FINDINGS: Patients reported assuming a more
      active role in medical decision making than originally intended, partners assumed
      a more passive role in decision making than originally intended, and all
      participants had lower levels of psychological distress at four months.
      CONCLUSIONS: Evidence supports the need to provide informational support to
      couples at the prostate cancer diagnosis to facilitate treatment decision making
      and lower levels of psychological distress. Future research is needed to evaluate
      this type of approach in the context of a randomized clinical trial design.
      IMPLICATIONS FOR NURSING: The personalized, computer-graphic printouts can
      provide clinicians with an innovative method of guiding information counseling
      and providing decisional support to men with prostate cancer and their partners.

PMID- 12515989
TI  - The advanced practice nursing role in a high-risk breast cancer clinic.
AB  - PURPOSE/OBJECTIVES: To describe the role of an oncology nurse practitioner in a
      breast cancer prevention clinic. DATA SOURCES: Published articles, abstracts, and
      book chapters and personal experience. DATA SYNTHESIS: Validated risk assessment
      models and genetic screening can be used to assess an individual's risk for
      breast cancer. Lifestyle changes and medical interventions can reduce that risk.
      CONCLUSIONS: Interventions for primary prevention of breast cancer soon may
      become one of the most effective means of reducing the incidence, morbidity, and
      mortality of breast cancer. IMPLICATIONS FOR NURSING: Advanced practice nurses in
      the oncology setting are ideal healthcare providers to assess patients' risk of
      breast cancer, determine physical findings that can influence that risk, provide
      risk education, synthesize existing data, and make recommendations for
      surveillance, pharmacotherapy, lifestyle changes, and genetic counseling and
      testing. Limitations in the existing data in cancer prevention provide excellent
      opportunities for nursing research.

PMID- 12515990
TI  - Methodologic issues in collecting data from debilitated patients with cancer near
      the end of life.
AB  - PURPOSE/OBJECTIVES: To report the experience of a group of researchers who have
      had a year of experience in a clinical trial with homecare hospice patients.
      SAMPLE: 150 hospice patients with cancer and their primary caregivers who were
      accrued to a National Cancer Institute-funded clinical trial focusing on quality
      of life. METHODS: The investigative team kept careful records of the numbers of
      patient/caregiver dyads accrued to the study and the reasons for nonaccrual as
      well as reasons for attrition. Data were analyzed using descriptive statistics.
      FINDINGS: During a nine-month period, the hospice admitted 2,517 patients; 75%
      had cancer and 95% had caregivers, making them eligible for the study. However,
      after further screening, only 19% were eligible for contact and only 5% finally
      were accrued to the study. For the 125 patient/caregiver dyads actually accrued
      to the study, baseline data were obtained on only 50% and evaluable follow-up
      data on only 50%. CONCLUSIONS: Accruing patients to clinical trials and retaining
      them when they are critically ill and near death are extraordinarily difficult
      tasks. The inability to recruit and retain subjects for clinical trials has
      implications for integrity of data, data analysis, success of the project, and
      the cost of conducting such projects in the future.

PMID- 12515991
TI  - Conducting intervention research through the Cancer Information Service: a
      feasibility study.
AB  - PURPOSE/OBJECTIVES: To determine the feasibility of conducting trials of
      educational interventions regarding pain and quality of life (QOL) with people
      who call the National Cancer Institute's Cancer Information Service (CIS).
      DESIGN: Descriptive. SETTING: North Central CIS, located at the University of
      Wisconsin Comprehensive Cancer Center in Madison. SAMPLE: Callers to the North
      Central CIS who self-identified as people diagnosed with cancer or as family
      members or friends of people diagnosed with cancer were eligible. 102 people with
      cancer and 103 significant others answered questions concerning the feasibility
      of a pain study, and 101 significant others completed questions about the
      feasibility of a QOL study. METHODS: Eligible CIS callers were invited at the end
      of usual service to participate in a research study. Those who agreed were asked
      structured questions regarding pain or QOL. MAIN RESEARCH VARIABLES: Response
      rate, length of time to complete recruitment, concerns about reporting pain and
      using analgesics, concerns about QOL, demographic variables, and willingness to
      join a hypothetical study. FINDINGS: The majority of callers had concerns about
      pain and QOL, and the vast majority (78%-89%) of participants indicated a
      willingness to join a future educational intervention study. CONCLUSIONS: Using
      subjects recruited through CIS, conducting trials of brief telephone
      interventions designed to help patients overcome barriers to pain management or
      assist families in addressing QOL concerns may be feasible. IMPLICATIONS FOR
      NURSING: Researchers may wish to consider the opportunities afforded by
      collaborating with CIS colleagues in planning and conducting studies of
      educational interventions.

PMID- 12515992
TI  - The role of oncology nursing to ensure quality care for cancer survivors: a
      report commissioned by the National Cancer Policy Board and Institute of
      Medicine.
AB  - PURPOSE: To examine the roles of oncology nurses in improving quality care for
      cancer survivors. DATA SOURCES: A content analysis of textbooks, journals, and
      key documents; surveys of graduate oncology nursing programs and the Oncology
      Nursing Society's Survivorship Special Interest Group; review of the nursing
      licensure examination and oncology nursing certification; review of undergraduate
      and graduate nursing standards; and review of currently funded nursing research.
      DATA SYNTHESIS: Ten critical content areas of cancer survivorship were used for
      the analysis: description of population of cancer survivors, primary care, short-
      and long-term complications, prevention of secondary cancer, detecting recurrent
      and secondary cancers, treatment of recurrent cancer, quality-of-life issues,
      rehabilitative services, palliative and end-of-life care, and quality of care.
      Although findings within each source indicated significant information related to
      the roles of nurses in caring for cancer survivors, deficits also were
      identified. CONCLUSIONS: Review of key literature and resources suggests
      significant contributions by oncology nursing over the past two decades to the
      area of cancer survivorship. IMPLICATIONS FOR NURSING: Support is needed to
      expand education and research to ensure quality care for future cancer survivors.

PMID- 12515993
TI  - Self-reported reasons men decide not to participate in free prostate cancer
      screening.
AB  - PURPOSE: To determine the reasons why men fail to participate in a free prostate
      cancer screening. DESIGN: Survey and secondary analyses using correlational
      design. SETTING: Community sites in the Southeastern United States. SAMPLE: The
      sample (N = 241) ranged in age from 40-68 years. Mean age was 50 years (SD =
      7.4). Most of the men were African American (79%) and married (70%). Almost half
      of the subjects (44%) earned between $9,601 and $25,020 per year. METHOD:
      Telephone survey of men who did not participate in initial prostate cancer
      screening after educational program. MAIN RESEARCH VARIABLES: Demographics, self
      reported reasons men decided not to participate in a free screening following a
      prostate cancer educational program, and predictors for subsequent participation
      in screening. FINDINGS: The main self-reported reason for not participating in a
      free prostate cancer screening opportunity was time problems. A significant
      relationship between income and physician problems existed among the men who did
      not participate. Twenty-one percent of the 241 men participated in a second
      opportunity for free prostate cancer screening. Men who cited "lost packet" as
      their reason for not participating in the first free screening were more than
      twice as likely to go for the second opportunity for free screening when offered
      another packet or voucher for a free screening with their physician of choice.
      CONCLUSIONS: "Time problems" was the most frequent self-reported reason men gave
      for failure to participate. Providing a follow-up phone call and vouchers a
      second time for reimbursement of the cost associated with a screening increased
      participation. Men often need assistance with locating physicians and nurse
      practitioners who will file for financial reimbursement. Appointment reminders
      are critical. IMPLICATIONS FOR NURSING: The findings of this study of the
      significant relationship between income and "physician problems" for not
      participating has implications for healthcare providers. Future programs could
      provide telephone follow-up with men and remail vouchers, as needed. In addition,
      men could be encouraged to designate one place in their households for health
      related papers (for safekeeping).

PMID- 12515994
TI  - Oncology emergency modules: spinal cord compression.

PMID- 12515995
TI  - Concurrent paclitaxel-cisplatin and twice-a-day irradiation in stage IIIA and
      IIIB NSCLC shows improvement in local control and survival with acceptable
      hematologic toxicity.
AB  - Non-small-cell lung cancer (NSCLC) has one of the highest death rates among the
      various forms of cancer. In attempts to improve on this unsatisfactory outcome,
      different radiation schedules and chemo-therapy agents have been examined in
      phase II or III studies. These have led to modest improvements in local control
      and survival, but combined therapies are associated with substantial hematologic
      toxicity. In this phase II study, 80 consecutive stage IIIA or IIIB NSCLC
      patients were treated with concomitant chemotherapy and twice-a-day irradiation
      in a total dose of 60 Gy in 1.5 Gy fractions. Patients scheduled for surgery
      received 45 Gy only. Paclitaxel (30 mg/m 2 ) on days 1-4 and cisplatin (100 mg/m
      2 ) on day 5 were administered in the first and fourth weeks of treatment.
      Granulocyte colony stimulating factor (30 ng/m 2 ) was given on days 10-15. The
      local control, the 1- and 2-year survival rates and the occurrence of acute
      hematologic toxicity in the non-surgically treated patients were examined. Fifty
      two patients were treated without and 28 with surgery. Among the non-surgically
      treated cases, 43 were evaluable for response and 47 for acute toxicity during a
      median follow-up of 22 months. The rate of local control was 65% (28/43), and the
      1- and 2-year survival rates proved to be 68% and 48%, respectively, with a
      median survival of 28 months. Severe acute grade 3-4 toxicities included grade 4
      leukopenia in 6 cases (13%), grade 3 leukopenia in 4 cases (9%), grade 3
      esophagitis in 3 cases (6%) and grade 3 anemia in 3 cases (6%). Our results and
      the relevant data from the literature support the application of twice-a-day
      irradiation with concomitant chemotherapy in stage IIIA and IIIB NSCLC. Local
      control and survival were improved relative to once-a-day irradiation with
      sequential or concomitant chemotherapy.

PMID- 12515996
TI  - Expression of CD44s in human colorectal cancer.
AB  - CD44s is a cell adhesion molecule, which belongs to the family of hyaluronan
      binding proteins. Anti-body to CD44s is used to establish the association of its
      expression with the clinicopathological characteristics of colorectal cancer
      using immunohistochemical methods. The aim of this study is to investigate the
      expression of the standard form of CD44 (CD44s) in colorectal cancer tissues as
      compared to adjacent normal colonic tissues. Furthermore, the level of expression
      of CD44s in colorectal cancer tissues was correlated with the degree of
      histological differentiation, Duke s classification, sex, size and site of the
      tumor. Immunohistochemical analysis for CD44s was carried out in 49 paraffin
      fixed sections of neoplastic colorectal tissues and non-neoplastic ones adjacent
      to the lesion, by the standard peroxidase-antiperoxidase method. Expression of
      these antigens were compared in normal and malignant epithelium and stromal
      cells. The results show that the level of CD44s in the epithelial and stromal
      cells was significantly higher in the colorectal cancer tissues than the normal
      ones. However, there was no association between the percentages of expressions of
      CD44s and the degree of histological differentiation, Duke s classification, sex
      or size of the tumor. There was however, a significantly higher expression of
      CD44s in the epithelium of rectal cancer than that of colonic cancer. This study
      indicates that the expression of CD44s is significantly higher in colorectal
      cancer tissues. However, further studies are required to understand its role in
      tumor progression and metastasis of this disease.

PMID- 12515997
TI  - Clinicopathologic evaluation of CDw75 antigen expression in colorectal
      adenocarcinomas.
AB  - CDw75, a B lymphocyte surface antigen, is a sialylated carbohydrate epitope,
      which is generated by the enzyme beta galactosyl alpha 2,6 sialyltransferase (Sia
      T1). In colon carcinomas, although higher levels of Sia-T1 has been described and
      found to be correlated with metastatic potential of tumor cells, the expression
      of CDw75 antigen still remains unknown. To address this issue, we investigated
      immunohistochemically CDw75 antigen expression in 195 colorectal adenocarcinomas
      and their nodal metastases. The correlation between CDw75 antigen expression with
      selected clinicopathologic variables was analyzed by using Chi-square and Fisher
      s exact tests. Positive staining was observed in 101 cases. Non-neoplastic mucosa
      was negative consistently. The frequency of positivity was decreased according to
      the degree of differentiation (p<0.001). Antigen expression was found to be
      associated with deeper penetration (p<0.006), positive lymph nodes (p<0.001),
      distant metastases (p<0.006) and advanced stage (p<0.001). Same relationships
      were detected in well and moderately differentiated tumors when CDw75
      immunoreactivity was evaluated in each histologic grade separately. Our findings
      indicate that CDw75 antigen expression may be a good indicator of the biological
      aggressiveness of colorectal adenocarcinomas especially in tumors with well and
      moderately differentiated morphology.

PMID- 12515998
TI  - Comparison of prognostic significance of serum 5-S-Cysteinyldopa, LDH and S-100B
      protein in Stage III-IV malignant melanoma.
AB  - 5-S-cysteinyldopa is a precursor of pheomelanin. S-100B protein is a low
      molecular weight, acidic, calcium binding, cytoplasmatic protein. LDH was defined
      as the most important serum parameter in disseminated melanoma. The aim of the
      present study was to compare the prognostic values of serum 5-S-Cysteinyldopa, S
      100B and LDH concentrations in Stage III-IV melanoma patients. Serum samples were
      taken from 179 Stage III-IV melanoma patients at diagnosis. Serum 5-S-CD
      concentrations were determined by HPLC, S-100B protein by immunoluminometric
      assay while LDH by UV kinetic method. The mean/median concentrations of LDH, S
      100B protein and 5-S-CD in Stage III patients ranged around the normal level. In
      Stage IV, the markers ranked as S100B = 5-S-CD > LDH for sensitivity, S-100B >
      LDH > 5-S-CD for specificity and LDH = S100B = 5-S-CD for positive predictive
      value, respectively. Furthermore, mean marker concentrations of patients with
      progressive disease differed significantly from nonprogresssive cases (when
      staging categories have been disregarded). Survival analysis indicated, that the
      initially elevated LDH and S-100B level in Stage IV disease predicts comparably
      short survival. Results of our study suggest that these serum marker values
      correlate well with Stages and disease progression. In Stage IV melanoma, the
      markers had appropriate sensitivity, high specificity as well as important
      positive predictive value. Among the studied serum markers S-100B protein and LDH
      proved to be similarly reliable in respect to the clinical outcome.

PMID- 12515999
TI  - Specificity of MOC-31 and HBME-1 immunohistochemistry in the differential
      diagnosis of adenocarcinoma and malignant mesothelioma: a study on environmental
      malignant mesothelioma cases from Turkish villages.
AB  - Histological diagnosis of malignant mesothelioma (MM) and differentiation from
      adenocarcinoma is often difficult. A number of clinical, radiologic, histologic
      and histochemical criteria have been used as diagnostic aids, but most cases
      cannot be readily classified on the basis of these characteristics. In recent
      years, a panel of immunohistochemical anti-bodies have been increasingly applied
      for the differential diagnosis of these two tumors. MOC-31 has been recently used
      as specific for adenocarcinomas while reacting with a minimal number of benign
      and malignant mesothelial proliferations, and HBME-1 has also been presented as a
      mesothelial cell marker. In this study, we aimed to show the importance of these
      two antibodies among the environmental MM cases from Southeastern Turkey. Fifty
      five cases of MM and twenty adenocarcinomas were included in this study.
      Histochemical (PAS, PAS-D, mucicarmine) and immunohistochemical (Keratin,
      EMA,CEA, MOC-31, HBME-1) stains have been performed on each case. Keratin was
      positive in all cases. EMA stained 50 of 55 MM and all the adenocarcinoma cases.
      According to our results, dPAS, mucicarmen, CEA and MOC-31 positivity was
      statistically significant in the diagnosis of adenocarcinoma whereas HBME-1 was
      demonstrable in most MM cases (52/55) and 11 adenocarcinoma cases. This study
      confirmed that in the diagnostic distinction between MM and adenocarcinoma,
      immuno-histochemistry is an important diagnostic tool, however, a panel of
      antibodies must be used rather than any single antibody. HBME-1 should be
      included in this panel; MOC-31 can be used where CEA is not available or to
      doublecheck the reactivity of this antibody.

PMID- 12516000
TI  - Prevalence of mycosis fungoides and its association with EBV and HTLV-1 in
      Pakistanian patients.
AB  - Mycosis fungoides (MF) is an indolent T cell lymphoma that is distinguished from
      other lymphomas by its initial appearance on the skin. The histologic diagnosis
      of MF may be difficult because there is significant overlap in the histologic
      features of neoplastic T-cell infiltrates and inflammatory dermatoses. This T
      cell neoplasm commonly occurs in a mixed, reactive background and can show only a
      subtle degree of cytologic atypia, rendering histologic diagnosis difficult. In
      this study MF constituted 0.86% of all non-Hodgkin s lymphoma (NHL) both T and B,
      as compared to the Western studies which have reported 0.5% prevalence for MF of
      all NHL. Polymerase chain reaction (PCR) technique was used to assess T-cell
      clonality in paraffin-embedded skin biopsies clinically and pathologically
      suspicious for early MF. Out of the 14 cases diagnosed as MF, amplifiable DNA was
      isolated from 6 cases, which were further studied for T-cell receptor (TcR) beta,
      gamma, and delta chain gene rearrangements. Clonal product was seen in 4 out of 6
      cases for beta, gamma, and delta TcR chain genes. Association for Epstein Barr
      virus (EBV) was observed in 3 out of 6 cases (50%) of MF. Although these 3 cases
      were positive for EBV by PCR, but were negative by in-situ hybridization (ISH).
      No heterogeneity was noted in these 3 cases of MF for BamHI E, K, N, and Z
      regions of EBV. All six cases were negative for HTLV-1 (tax region) by PCR. It
      was concluded that the prevalence of MF in Pakistani population is comparable to
      the Western data, and that EBV association to MF cases was higher than in Western
      studies.

PMID- 12516001
TI  - Primary neuroendocrine carcinoma of the mediastinum.
AB  - A mediastinal mass was found in a 37 year old male who presented with fever,
      weight loss and fatigue. The chest CT revealed a 9x6x4 cm well circumscribed mass
      located paratrachaelly in the upper mid-mediastinum. The mass was removed by
      right thoracotomy. Macroscopically the tumor weighed 195 g and measured 9x6x4 cm.
      Microscopically the tumor consisted of small blue cells in solid and trabecular
      pattern. Immunohistochemical studies performed for differential diagnosis of
      small blue cell tumors. The tumor was diagnosed as primary neuroendocrine
      carcinoma of the mediastinum. This case is presented for its rare recurrence in
      that particular location.

PMID- 12516002
TI  - Combined occurrence of prostate carcinoma and malacoplakia.
AB  - This is a case of a 56-year-old male patient suffering from a combination of
      prostate carcinoma and malacoplakia. A 56-year-old male patient was admitted in
      our Department because ischuria due to the enlargement of the prostate. Perineal
      needle biopsy was done resulting carcinoma of prostate. Radical prostatectomy was
      performed. Histology proved carcinoma and a great part of the enlarged prostate
      consisted of malacoplakia. Questions related to the morphology, tissue structure
      as well as diagnosis are briefly surveyed. This is the first report on the rarely
      occurring combination of prostate carcinoma and malacoplakia treated by radical
      retropubic prostatectomy.

PMID- 12516005
TI  - The biology of aging.
AB  - In humans, aging is inexorable. The progressive decrease in physiological
      capacity and the reduced ability to respond to environmental stresses lead to
      increased susceptibility and vulnerability to disease. Consequently, mortality
      due to all causes increases exponentially with aging. Attempts at understanding
      the causes of aging are limited by the complexity of the problem. Aging changes
      are manifest from the molecular to the organismic level; environmental factors
      affect experimental observations; secondary effects complicate elucidation of
      primary mechanisms; and precisely defined, easily measurable biomarkers are
      lacking. No one unifying theory may exist, since the mechanisms of aging could be
      quite distinct in different organisms, tissues, and cells. Evolutionary pressures
      have selected for successful reproduction, making it likely that the post
      reproductive physiology of an organism (i.e., aging) is an epigenetic and
      pleiotropic manifestation of the optimization for early fitness. Indeed,
      antagonistic pleiotropy, wherein genes that enhance early survival and function
      but are disadvantageous later in life, may play an overriding role in aging.
      Theories of aging can be divided into two general categories: stochastic and
      developmental-genetic. These are not mutually exclusive, particularly when
      considering the free radical/mitochondrial DNA theory of aging. Increasing
      evidence suggests that cellular senescence and organismic aging are
      antagonistically pleiotropic manifestations of evolutionary pressures to prevent
      malignant transformation. In other words, aging may be the price we pay to avoid
      cancer. The beneficial paradox may be that the maximum lifespan potential of
      humans may have been achieved, in part, due to our ability to grow old.

PMID- 12516006
TI  - Inflammatory arthritis in the elderly.
AB  - The three most common inflammatory arthritic conditions affecting the elderly are
      reviewed, along with current information about the various treatments.

PMID- 12516003
TI  - Molecular pathology of tumor metastasis. II. Molecular staging and differential
      diagnosis.
AB  - Molecular Pathology of Tumor Metastasis With the development of non-invasive
      methods, diagnosis of metastasis from various solid malignancies has become a
      routine task for diagnostic pathology. However, the differential diagnosis
      between primary and metastatic cancers and the precise identification of various
      metastatic cancer types requires the coordinated use of various morphological
      (light- and electron microscopic-), immunological and molecular techniques. The
      detection of the lymphatic spread of the primary tumor may now based on the
      sentinel lymph node technology while the identification of the hematogenous
      progression may be based on the analysis of the peripheral blood and the bone
      marrow. More and more frequently these techniques employ highly sensitive
      immunological and molecular techniques. Accordingly, clinical staging is now
      confronted with the results of molecular staging, where the only techniques which
      are able to detect cancer cells are immunocytochemistry or nucleic acid-based
      methodology. Although several clinical studies have provided evidences for the
      impact of the immunocytochemistry-based identification of micrometastases on the
      survival of patients with various type of cancers, none of these methods have
      become part of standard diagnostic protocols. Although more sensitive molecular
      techniques are being introduced to identify micrometastasis, their clinical
      significance is yet unknown. Multicentric clinical trials are now warranted to
      establish the clinical impact of molecular staging in various cancer types.
      Without the integration of these methods into the prognostic/predictive
      pathological protocols it is difficult to envision significant improvement in the
      results of cancer therapy.

PMID- 12516007
TI  - Stroke in the elderly.
AB  - Stroke is one of the oldest but least understood diseases, and it is one of the
      major public health problems facing the elderly. Recent epidemiological
      investigations have found that the incidence of stroke has been underestimated by
      about 50%, and that the burden of disease is highest in minority populations.
      Recent clinical and basic neuroscience research indicates that stroke is neither
      unpredictable nor irreversible. Many risk factors for stroke are readily
      identifiable, and evidence-based treatment may be used to reduce the likelihood
      of stroke among those at risk. Rapid diagnosis and evaluation of stroke and
      transient ischemic attack and their treatment, including surgery,
      anticoagulation, antiplatelet and other medical therapies, reduce the chance of
      recurrence. More aggressive treatment of blood pressure, even among patients who
      are not necessarily hypertensive, may also reduce the risk of future strokes.
      Once ischemic stroke has occurred, emergent therapy using thrombolysis may
      significantly reduce disability, even among the elderly. This review presents an
      update on definitions of stroke and its subtypes, stroke epidemiology, and the
      results of recent studies of stroke prevention and acute treatment.

PMID- 12516008
TI  - Overview: depression in the elderly.
AB  - Depression in the elderly population is a major public health problem. It has a
      high prevalence, is frequently co-morbid with medical illnesses, impacts
      negatively on quality of life, increases the number of visits to different
      medical services, and carries a high risk of suicide, especially in men. Imaging
      studies have increased our understanding of the biological mechanisms of
      depression in the elderly. Depression is sometimes difficult to diagnose in the
      elderly. It should be differentiated from apathetic states ( negative syndrome ),
      and its treatment requires knowledge of specific physiological changes that occur
      in this age group. Geriatric depression is more somatic and less ideational than
      depression in other age groups. Acute treatments with various antidepressant
      medications, augmentation strategies, electroconvulsive treatments, and
      psychotherapy must be coupled with maintenance strategies to prevent recurrences,
      which are common.

PMID- 12516009
TI  - Review of dementia.
AB  - Elderly persons are at increased risk for developing dementia, and this risk
      increases with age. It is important to understand the following points: (a). how
      to diagnose dementia; (b). the etiology of the most common dementias (including
      Alzheimer s disease, ischemic vascular dementia, and diffuse Lewy body dementia);
      (c). some medical conditions which could contribute to symptoms of dementia; (d).
      the pathophysiology of Alzheimer s disease; and (e). management problems faced by
      caregivers for dementia patients. This review aims to educate clinicians to focus
      on caregivers issues and the need for long-term planning.

PMID- 12516010
TI  - Urinary incontinence in the geriatric population.
AB  - BACKGROUND: Urinary incontinence is a widespread, yet potentially treatable,
      problem in the geriatric population. METHODS: We reviewed the geriatric and
      urologic literature to provide an update on the definition, diagnosis, and
      treatment of geriatric urinary incontinence. RESULTS: Urinary incontinence
      affects 15-30% of elderly individuals in the community and 50% of those living in
      nursing homes. Both age and gender affect bladder function, and incontinence
      affects females and males in a ratio of 2:1. Incontinence can be classified as
      urge, stress, overflow, functional, or mixed. There are many reversible causes of
      incontinence, and a thorough history and physical examination, including a
      complete voiding history and a tailored neuro-urologic examination, are required
      for accurate diagnosis. Treatment options include behavioral modification,
      medical therapy with anticholinergics or hormone replacement, and surgical
      intervention. CONCLUSIONS: Urinary incontinence, due to many causes, is a
      widespread problem among the elderly. Yet many of these causes are reversible
      with appropriate treatment, often by the primary care provider. Some patients may
      require urologic referral for sophisticated urodynamic studies and possible
      surgical intervention, in select cases.

PMID- 12516011
TI  - Why elder abuse continues to elude the health care system.
AB  - Elderly men and women of all socioeconomic and ethnic backgrounds are vulnerable
      to mistreatment, and most often it goes undetected. For many elderly victims of
      abuse, the hospital is the only potential site for outside contact and support.
      An elder abuse program has been created at The Mount Sinai Hospital in New York
      City, and funding was granted to assist victims with compensation claims; provide
      counsel and advocacy for victims; and provide support via ongoing telephone
      contact and referrals to community agencies. Simultaneously, hospital-wide
      educational seminars and rounds have provided the staff and students with
      information concerning detection of abuse and neglect. Over a 2-year period, 182
      cases were identified and assessed. More than 50% of these cases involved
      patients with a diagnosis of memory impairment. Five percent of the cases
      involved a long history of domestic violence. In most cases a family member was
      identified as the abuser, and in a majority of instances the victim either denied
      the suspected abuse or tried to rationalize the behavior of the abuser. Patients
      were afraid of reporting abuse or changing their situation, despite being
      informed of possible resources. To combat this escalating problem in our growing
      elderly population, interdisciplinary collaboration between physicians and social
      workers is often crucial. Communication via the medical record can be key to
      monitoring patients in the community. There also needs to be ongoing education of
      all hospital staff in an effort to continually heighten awareness of this
      problem.

PMID- 12516012
TI  - [Johann-Peter-Frank Medal 2002 Award -- laudatio for Dr. Burkhardt Jaeschke].

PMID- 12516013
TI  - [Communal health targets as seen by the population and by experts. Two inquiries
      in the Ennepe-Ruhr district].
AB  - INTRODUCTION: Health planning at the community level depends largely on the
      consensus of participants and the support by local politicians and the public.
      For a successful coordination it is important to integrate the common opinions
      and priorities of the partners. The aim of the project was to determine the
      common priorities of the general public and local health experts. The results
      should be the basis for the development of local health planning. MATERIAL AND
      METHODS: 1181 representative selected adult inhabitants of the Ennepe-Ruhr
      district were interviewed by phone about their expectations regarding local
      health policy. At the same time the members of the local health conference (n =
      28) were asked to fill in a questionnaire on the same subjects. RESULTS: The 10
      North Rhine-Westphalian Health targets are largely unknown by the public. The
      aims 'Fight against Cancer' (75%), 'Minimising the health effects of drug abuse'
      (53%) and 'Reduction of heart diseases' (53%) were seen as most important.
      Emphasised were the quality of nursing and declining services of the health care
      system due to financial problems. General targets like 'More information of
      patients' or 'Strengthening of patient participation' were considered as less
      important. By contrast, the health experts stated structural and planning
      elements as central NRW-Health Targets. Ranked first are the topics 'Improvement
      of health promotion' and 'Empowerment and quality of health care'. DISCUSSION:
      The results of two polls were important for the planning of the work in the local
      health conference. Remarkable are the discrepancies between the two groups. While
      the citizens focussed on concrete health problems, the experts, concentrated on
      structural aspects of the health system. The complex of 'Old Age and nursing' and
      'Aspects of/deficits in primary health care' were important for both groups. The
      local health coordination is to develop a concrete agenda to integrate these
      results. The theoretical basis of community health policy is discussed.

PMID- 12516014
TI  - [Progression of the pension-application process in psychosomatic patients].
AB  - Psychosomatic disorders have become increasingly important as a reason for
      premature retirement. To identify specific characteristics of pension applicants,
      we broke a random sample consisting of 1,109 patients admitted to Burg Hospital
      within the framework of psychosomatic rehabilitation programmes into three main
      groups: a) patients who had not applied for any kind of pension benefits and
      'high-risk groups' of pension aspirants who b) had either already submitted an
      application or c) intended to do so. The comparison of the sociomedical data from
      the two groups showed that the high-risk group contained a markedly larger
      percentage of unemployed patients and patients who had been on sick leave for
      longer periods. The average age of the pension aspirants was higher. Moreover,
      this group contained a larger percentage of male patients than did the non
      applicant group. An assessment of rehabilitation potential uncovered a distinctly
      depressed potential in the high-risk group. Moreover, the assessment of
      individual patient performance conducted at the end of each rehabilitation
      programme yielded significantly lower scores for the high-risk groups in
      comparison with the non-applicant group. On the basis of the decrease in
      symptoms, it is evident that only small therapeutic success can be achieved with
      these patients, who as a group display a significantly lower therapeutic
      motivation than their non-applicant counterparts. Furthermore, there was a higher
      incidence of recurrent depressive disorders and somatic pain disorders in the
      high-risk groups. The development of pension aspirations can be described as a
      process starting with a disorientation phase, proceeding to an ambivalence phase
      and culminating in a rigid terminal phase. Patients who have reached this stage
      are generally resistant to rehabilitation efforts. For this reason, early
      recognition of pension aspirations is of critical importance.

PMID- 12516015
TI  - [Migration-specific expertising in the spheres of tension between medicine, law,
      psychology and politics -- report on an interdisciplinary meeting of experts].
AB  - The 4th conference of transcultural medical appraisal was organized once again by
      the ethno-medical center in Hannover on 2nd and 3rd of November, 2001. For the
      first time, medical estimators and decision-makers from the spheres of medicine,
      psychology, law and administration got together thematically and
      interdisciplinary. As to the public health authorities, the intensive discussion
      and working session on the topic of deportation, transportability and asylum was
      of high relevance. The specific working group included judges, clinical and
      public health physicians, psychologists, migration authority officials and
      representatives of migrant organisations. In full agreement finally it was
      pointed out that medical or psychological estimation concerning asylum and
      deportation should remain in the hands of the public health authorities because
      of their expert knowledge, experience and full independence in the sphere of
      medical and psychological appraisal.

PMID- 12516016
TI  - [In the consumers' interest: precautionary principles for protection against
      electromagnetic fields].
AB  - The considerable increase in using mobile communication which will increase when
      new technologies, such as UMTS, are introduced has resulted in further public
      interest concerning the possible health risks from electromagnetic fields of
      cellular phone networks. In view of evaluating the scientific state-of-the art,
      it has been shown that based on the available scientific results, the individual
      risk in view of proved health consequences is considered low. There are, however,
      indications of biological effects of high-frequency electromagnetic fields, even
      at intensities below the currently applied limit values or recommendations for
      limit values. Although the health relevance of these effects is still unclear,
      they give reason to precautionary measures with the object to minimise possible
      health risks which might affect a large number of persons. The precautionary
      measures recommended by the Federal Office for Radiation Protection include three
      principles: 1. Exposure of the general public to electromagnetic fields should be
      as low as possible. This applies for both the fixed parts of cellular phone
      networks and for mobile phones. 2. The population should be informed of risks in
      an objective and comprehensive way and be involved in the decisions on the
      construction and operation of cellular phone networks. 3. Scientific
      uncertainties should be reduced by means of well-directed research programmes.
      These precautionary measures and the significance of limit values are explained
      below.

PMID- 12516017
TI  - [Studying school beginners in western and eastern Germany: allergy trends and
      sensitisations 1991-2000].
AB  - AIM: Aim of the study is to examine the hypotheses of a steeper increase in
      allergies and allergic sensitisations in East than in West German children
      between 1991 and 2000. METHOD: Between 1991 and 2000 we yearly repeated cross
      sectional studies (SAWO: Study on school beginners) and asked 36,645 parents
      about diagnoses and symptoms of allergies in their six-year old children
      (response: 79 %). The study was done in Leipzig, Halle, Merseburg, Magdeburg,
      small towns in the Altmark region, Duisburg, Essen, Koln and Borken during
      spring. An allergological investigation was included 1991, 1994, 1997 and 2000.
      Dermatologists diagnosed a prevalent atopic eczema, administered a skin prick
      test (n = 7,229) and blood was taken for the determination of specific IgE
      antibodies against common allergens (n = 7,714, RAST). Odds Ratios (OR) for trend
      were calculated separately for the data from East and West Germany and are given
      along with their 95% confidence intervals. RESULTS: Allergies and their symptoms
      (exception: atopic eczema) were less prevalent in East German children born
      before the reunification than in West German ones. In East as well as in West
      Germany bronchial asthma was diagnosed more often in 2000 than in 1991 (OR East:
      2.42 [1.78-3.28] West: 2.07 [1.43-3.00]). In contrast the prevalence of atopic
      eczemas was more than halved between 1991 and 2000. Of all symptoms and diagnoses
      of allergies only hay fever and its symptoms showed an upward trend in East
      Germany which was steeper than the trend in West Germany (OR East: 4.41 [3.17
      6.13] West: 1.74 [1.19-2.57]). This can partly be explained by a parallel trend
      in sensitisation against grass pollen. CONCLUSION: The spatial and temporal
      pattern of the allergic diseases bronchial asthma, hay fever and atopic eczema in
      six-year old children from Germany is different. The expected steeper increase of
      allergies in East than in West Germany could only be shown for hay fever.

PMID- 12516018
TI  - [Efforts concerning the health target of age-specific coverage levels in over 90%
      of the population of Saxony-Anhalt].
AB  - At the first health conference in Saxony-Anhalt held at Magdeburg in March 1998
      six health objectives were defined, among them the objective to increase to 90%
      the vaccination coverage level of the population. To achieve this goal the
      participants decided to establish a working group composed of representatives of
      20 institutions and organisations interested in vaccination strategies. Subgroups
      were constituted for the following components of the objective: improvement of
      the data basis, completion of the special knowledge of physicians and other
      medical personnel, public information campaigns, and improvement of the
      structural framework. More than 50 actions per year were initiated or co
      ordinated taking into account the special profiles of the institutions and
      organisations involved. In this way a better identification of the participants
      with the project was achieved and waste of strength and time was avoided. The
      data basis was assessed using generally available or newly created parameters
      such as the incidence of notified vaccine-preventable diseases, measles
      seroprevalence, and vaccination coverage levels among children aged 5-6 years.
      Approaches to target group related activities of the working group were derived
      from these parameters. The most remarkable results of these activities include
      the definition of age specific vaccination coverage levels, the establishment of
      a certificate for physicians who have completed a vaccination training course, a
      monthly press release on vaccination subjects, the design of a poster
      presentation, the composition of foil-based age group specific lectures, and the
      establishment of frame conditions for a recall system for practising physicians.
      The first hurdles on the way to a high age specific vaccination coverage levels
      have been taken. Further work must be done to improve the use of offered
      vaccinations and to complete the available data. Therefore, additional target
      group-related projects and actions are planned for the years to come.

PMID- 12516019
TI  - [Sense and nonsense of exposure prophylaxis in communal club installations for
      children and adolescents -- a contribution to the implementation of the German
      Defence Against Infection law from a point of view of preventive paediatrics].
AB  - The protection against infections in facilities of the community for infants and
      children, such as kindergarten, schools and training centres, results first of
      all from the vaccination practice and hygiene practices. Pertussis, varicella and
      tuberculosis are examples for this. In some cases the transient avoidance of
      contacts and the intensified integration of the parents could contribute to the
      prevention of an infection, e. g. strepptococcus A infections and head louses.
      The consequential realization of the recommendation of the STIKO (expert panel
      for vaccination guidelines; http://www.rki.de/GESUND/STIKO/STIKO.HTM) is one of
      the main pillars of protection by vaccination. Vaccine coverage may also be
      improved by including these paragraphs in the statutes of day nurseries. Before
      integration of children into such facilities it should be necessary to verify
      that there are no doubts about the health conditions. This could be confirmed by
      presenting the vaccination or check-up card.

PMID- 12516020
TI  - [Environmental surveys in the areas of Bitterfeld, Hettstedt and a comparative
      area in 1992-2000].
AB  - The aim of the environmental epidemiological study was to determine possible
      adverse effects on the health of children in the environmentally polluted areas
      of Bitterfeld and Hettstedt compared to the less polluted area of Zerbst (Eastern
      Germany). The changes of the health parameters were recorded together with the
      environmental changes during the time period of 6 years. The study design
      consisted of three repeated regional cross-sectional studies in 1992/93, 1995/96
      and 1998/99. In total, 7,611 questionnaires could be analysed (participation
      rate: 89%, 75% and 75%). Children living in the most polluted area of Hettstedt
      had a noticeable higher risk for non-allergic respiratory diseases and symptoms
      compared to children living in the control area of Zerbst. From 1992 to 1999 a
      statistically significant decrease in the prevalences of these health outcomes
      was found. Children without indoor pollutants in their homes had the greatest
      benefit by the improvement of ambient air quality. The increase in lung function
      (FVC, FEV1) also underlines the improvement of the respiratory health. Children
      living in the polluted areas reported allergies more often (physician's
      diagnosis, allergy specific antibodies). The prevalence of asthma, the bronchial
      hyperreactivity and atopic eczema was increased within the observational period
      of 6 years. An increased prevalence was also shown for more severe allergic
      sensitisation (RAST classes > 17.5 kU/l), while the prevalence of hay fever
      increased slightly on a non-significant level. The burden with lead and cadmium
      was higher in children living in polluted areas and decreased during the study
      period except for 1997 where the lead concentration in blood increased according
      to the higher lead concentration in settled dust in Hettstedt at that time.

PMID- 12516021
TI  - [Tetrachloroethylene in drycleaning shops].
AB  - Tetrachloroethylene -- also known as Perchloroethylene, PCE and perc -- is a
      chlorinated hydrocarbon with the formula C2 Cl4, which is widely used as a
      degreasing solvent in drycleaning. This resulted in environmental pollution in
      apartments and groceries adjacent to drycleaners. The highest exposure levels
      were measured in the eighties of the last century. One case from Goslar is
      presented with human biomonitoring and remedial actions. The second German
      Federal Immission Control Ordinance (2. BImSchV) on limitation of emission of
      volatile halogenated hydrocarbons from 1990 resulted in new methods of
      drycleaning and a substantial elimination of environmental and health problems.

PMID- 12516022
TI  - [Consequences and challenges due to bioterrorist attacks].
AB  - Ever since the terrorist attacks of 11 September 2001 and the cases of
      inhalational anthrax and other types of anthrax caused by attacks with anthrax
      spores, responsible authorities and experts must reckon with bioterrorist attacks
      conducted with much greater criminal "drive" and greater financial resources than
      had been imagined so far. This consideration triggered cautionary measures in
      Germany and Europe as briefly summarised here. For more detailed information
      please refer to internet (www.rki.de) and see the references given below.

PMID- 12516023
TI  - [Risk management and risk communication from a laboratory point of view].

PMID- 12516024
TI  - Microbial resistance: bacteria and more.

PMID- 12516025
TI  - The global impact of drug resistance.
AB  - Measuring the impact of drug resistance is an important step in understanding the
      scope of the problem and formulating policies to limit the emergence and spread
      of resistant organisms. Studies have focused on measuring the increased costs,
      morbidity, and mortality in patients with infections due to resistant versus
      susceptible organisms. These have generally found that resistance worsens
      outcomes. By focusing only on infected patients, however, they may understate the
      impact of resistance. It is important to recognize that resistance also affects
      the treatment of individuals with nonresistant organisms. In areas with high
      rates of resistance, physicians and governments have changed empiric therapy for
      malaria, tuberculosis, acute respiratory infections, and other diseases,
      increasing overall treatment costs. In some instances, these costs may exceed
      those attributable to treatment failure.

PMID- 12516026
TI  - Bacterial resistance: origins, epidemiology, and impact.
AB  - The basic mechanisms of antibacterial resistance are well known, but critical new
      aspects continue to be discovered. Recently discovered factors with major
      implications for the emergence, dissemination, and maintenance of resistance
      include multidrug efflux, hypermutability, integrons, and plasmid addiction. Some
      resistances are widespread and others local, with prevalence rates often worst in
      newly prosperous countries and in those specialist units where antibacterial use
      is heaviest. Multidrug-resistant epidemic strains are critical to the total
      accumulation of resistance (e.g., among Streptococcus pneumoniae, methicillin
      resistant Staphylococcus aureus, Klebsiella pneumoniae), but it remains unclear
      why some bacterial lineages achieve epidemic spread whereas others that are
      equally resistant do not. The correlation between in vitro resistance and
      treatment failure is imperfect, but resistance undoubtedly increases mortality,
      morbidity, and costs in many settings. Recent concern has led to a plethora of
      governmental and agency reports advocating less antibacterial use, better
      antibacterial use, better infection control, and the development of new
      antibacterials. The evidence that better prescribing can reduce resistance rates
      is mixed, and although changes to hospital regimens may reduce one resistance
      problem, other opportunistic bacteria may fill the vacant niche. Overall, the
      best that can reasonably be anticipated is an improved balance between the
      accumulation of resistance and new antibacterial development.

PMID- 12516027
TI  - Tuberculosis drug resistance: a global threat.
AB  - Resistance to antituberculosis drugs has been a problem since the era of
      chemotherapy began. After dramatic outbreaks of multidrug-resistant tuberculosis
      (MDR-TB) in the early 1990s, resistance became recognized as a global problem.
      MDR-TB now threatens the inhabitants of countries in Europe, Asia, Africa, and
      the Americas. An understanding of the molecular basis of drug resistance may
      contribute to the development of new drugs. Management of MDR-TB relies on prompt
      recognition and treatment with at least 3 drugs to which an isolate is
      susceptible.

PMID- 12516028
TI  - Antifungal drug resistance.
AB  - The increasing incidence of invasive fungal infections is the result of many
      factors, including an increasing number of patients with severe
      immunosuppression. Although new drugs have been introduced to combat this
      problem, the development of resistance to antifungal drugs has become
      increasingly apparent, especially in patients who require long-term treatment or
      who are receiving antifungal prophylaxis, and there is growing awareness of
      shifts of flora to more-resistant species. The frequency, interpretation, and, in
      particular, mechanism of resistance to current classes of antifungal agents,
      particularly the azoles (where resistance has climbed most prominently) are
      discussed in this review.

PMID- 12516029
TI  - Prevention of resistance: a goal for dose selection for antimicrobial agents.
AB  - Drug-resistant microorganisms have become a major problem around the world. In
      nosocomial and community settings, many important pathogens have demonstrated
      high-grade resistance to many of our most important agents. In addition, the
      adverse impact of resistance has not been limited to the bacterial realm. In
      chemotherapy to treat human immunodeficiency virus (HIV) and other viral
      diseases, resistance has become a major problem. We are starting to see the
      beginnings of a resistance problem, even among fungi. Strangely, little attention
      has been focused on the impact of dosing on the probability with which emergence
      of resistance occurs. After delineation of the pharmacodynamically linked
      variable, it is possible to generate dosing regimens that can lower the
      probability of resistance. In addition, circumstances exist in which combination
      therapy may be required (e.g., therapy of HIV and tuberculosis). Here, too, it is
      possible to optimize therapy to prevent resistance by understanding how the drugs
      in the regimen interact. We can do better with our choices of dose, schedule, and
      combinations of agents. We will need to lower the probability of resistance and
      maintain the utility of the drugs currently in our therapeutic armamentarium.

PMID- 12516030
TI  - Genomewide linkage analysis identifies polymorphism in the human interferon-gamma
      receptor affecting Helicobacter pylori infection.
AB  - Helicobacter pylori is considered the most prevalent infectious agent among
      humans, and it causes gastric inflammation, gastroduodenal ulcers, and a risk of
      gastric cancer. We performed a genomewide linkage analysis among Senegalese
      siblings phenotyped for H. pylori-reactive serum immunoglobulin G. A multipoint
      LOD score of 3.1 was obtained at IFNGR1, the gene that encodes chain 1 of the
      interferon-gamma (IFN-gamma) receptor. Sequencing of IFNGR1 revealed -56C-->T,
      H318P, and L450P variants, which were found to be associated with high antibody
      concentrations. The inclusion of these in the linkage analysis raised the LOD
      score to 4.2. The variants were more prevalent in Africans than in whites. Our
      findings indicate that IFN-gamma signaling plays an essential role in human H.
      pylori infection, and they contribute to an explanation of the observations of
      high prevalences and relatively low pathogenicity of H. pylori in Africa.
      Moreover, they provide further support for the value of genomewide linkage
      studies in the analysis of susceptibility to infection and other complex genetic
      traits.

PMID- 12516032
TI  - Tumor angiogenesis and accessibility: role of vascular endothelial growth factor.
AB  - Solid tumors consist of several components, including normal and stromal cells,
      extracellular matrix, and vasculature. To grow and metastasize, tumors must
      stimulate the development of new vasculature through a process known as
      angiogenesis. Unlike normal blood vessels, tumor blood vessels are chaotic,
      irregular, and leaky, which leads to uneven delivery of nutrients and therapeutic
      agents to the tumor. Conventional therapies target neoplastic cells within a
      tumor; however, tumor vasculature is emerging as an important target for
      anticancer therapy. Antiangiogenic therapy offers several potential advantages as
      an approach to cancer treatment, notably physical accessibility and genetic
      stability of target cells. Vascular endothelial growth factor (VEGF), a central
      mediator of angiogenesis, has emerged as an important target for antiangiogenic
      therapy. In preclinical studies, treatment of human tumor xenografts in
      immunodeficient mice with the anti-VEGF monoclonal antibody A4.6.1 led to reduced
      tumor vessel permeability and caused vascular regression. The reduced vascular
      permeability, resulting from inhibition of VEGF, led to increased delivery of
      oxygen and therapeutic agents to tumors. Anti-VEGF therapy was effectively
      combined with other treatment modalities, including radiation, antihormonal,
      antibody, and chemotherapies in multiple preclinical models. Currently, several
      phase 3 clinical trials in various cancer types are under way to establish the
      efficacy of antiangiogenic therapy with a recombinant humanized anti-VEGF
      monoclonal antibody, bevacizumab (Avastin, rhuMAb-VEGF; Genentech, South San
      Francisco, CA), in combination with chemotherapeutic agents.

PMID- 12516033
TI  - Role of vascular endothelial growth factor in physiologic and pathologic
      angiogenesis: therapeutic implications.
AB  - Angiogenesis, or formation of new blood vessels from pre-existing ones, is
      essential for normal development and wound healing/reproductive functions in
      adults. Abnormal regulation of angiogenesis has been implicated in the
      pathogenesis of several disorders, including cancer. Vascular endothelial growth
      factor (VEGF)-A is a pivotal stimulator of angiogenesis because its binding to
      VEGF receptors has been shown to promote endothelial cell migration and
      proliferation, two key features required for the development of new blood
      vessels. In addition, VEGF-A increases vascular permeability, which may also
      contribute to angiogenesis and tumor growth. Recognition of the central role of
      VEGF-A in angiogenesis has led to the hypothesis that its inhibition may
      represent a novel and effective approach to the treatment of cancer and other
      conditions characterized by pathologic angiogenesis. Several lines of evidence
      support this idea, and early clinical experience with the humanized anti-VEGF-A
      monoclonal antibody bevacizumab (Avastin, rhuMAb-VEGF; Genentech, South San
      Francisco, CA) has been encouraging. Clinical efficacy of antiangiogenic therapy
      with bevacizumab is being evaluated in several phase 3 trials in various types of
      cancer, as well as in patients with age-related macular degeneration.

PMID- 12516034
TI  - Role of angiogenesis in tumor growth and metastasis.
AB  - Angiogenesis is required for invasive tumor growth and metastasis and constitutes
      an important point in the control of cancer progression. Its inhibition may be a
      valuable new approach to cancer therapy. Avascular tumors are severely restricted
      in their growth potential because of the lack of a blood supply. For tumors to
      develop in size and metastatic potential they must make an "angiogenic switch"
      through perturbing the local balance of proangiogenic and antiangiogenic factors.
      Frequently, tumors overexpress proangiogenic factors, such as vascular
      endothelial growth factor, allowing them to make this angiogenic switch. Two
      strategies used in the development of antiangiogenic agents involve the
      inhibition of proangiogenic factors (eg, anti-vascular endothelial growth factor
      monoclonal antibodies) as well as therapy with endogenous inhibitors of
      angiogenesis, such as endostatin and angiostatin. Therapy with endogenous
      angiogenic inhibitors such as endostatin and angiostatin may reverse the
      angiogenic switch preventing growth of tumor vasculature. Preclinical studies
      have shown that endostatin effectively inhibits tumor growth and shrinks existing
      tumor blood vessels. Phase 1 clinical trials of endostatin and angiostatin are
      ongoing, and preliminary results show minimal toxicities.

PMID- 12516036
TI  - Complementary and alternative medicine: opportunities and challenges for cancer
      management and research.
AB  - Given the widespread use of diverse complementary and alternative medicine (CAM)
      approaches by cancer patients, research to establish their safety and efficacy is
      critical as is improved patient-physician communication about their possible
      risks and benefits. The mission of the National Center for Complementary and
      Alternative Medicine (NCCAM) is to support exacting research and disseminate
      clear and compelling information on CAM. Although many of the challenges facing
      such research are not unique to CAM, these approaches do present unique
      challenges, but the opportunities are many for prevention, palliation, and even
      treatment. Using the current research portfolio of NCCAM to illustrate how the
      field may mature, this report summarizes the challenges facing CAM investigators,
      the most fruitful areas for exploration, and existing information resources.

PMID- 12516037
TI  - Complementary and alternative medicine research: a National Cancer Institute
      perspective.
AB  - The widespread use of a variety of nutritional, psychological and natural medical
      approaches, collectively termed complementary and alternative medicine (CAM), has
      been well documented. Recent surveys demonstrate that between 9% and 91% of US
      cancer patients use CAM therapies at some time after their diagnosis. Despite
      their extensive use, there is a paucity of data available to indicate whether
      these practices are efficacious and safe. The National Cancer Institute (NCI) is
      implementing programs to increase the amount and quality of cancer CAM research,
      support the production of high-quality CAM cancer information, and facilitate the
      dialog between CAM practitioners and cancer researchers.

PMID- 12516038
TI  - Use of the best case series to evaluate complementary and alternative therapies
      for cancer: a systematic review.
AB  - The best case series (BCS) is a retrospective chart review that describes a
      series of patients who all appear to have benefitted from the treatment under
      study. The BCS has been advocated as the first research step for evaluating
      complementary and alternative medicine (CAM) treatments for cancer. However, the
      research value of the BCS has not been assessed. To address this deficiency, the
      present study evaluates the primary characteristics of the BCS process through a
      systematic review of the English language scientific literature. Twenty-four
      individual BCS investigating 16 unique CAM treatments for cancer were identified.
      About half of the BCS reported evidence of tumor regression in association with a
      particular CAM treatment, but only six contained documentation adequate for
      publication in peer-reviewed journals. For these six BCS the number of responders
      per BCS ranged from 2 to 12 (median, 3.5), the proportion of responders in the
      total number of evaluated cases varied from 6% to 100% (median, 40%), and the
      proportion of evaluated cases to identified cases ranged from 18% to 53% (median,
      29%). The primary factors confounding the identified BCS were lack of
      documentation of disease and/or the use of concurrent or recent conventional
      treatment. Despite these general deficiencies, four BCS (antineoplastons,
      hydrazine sulfate, laetrile, and Kelly-Gonzalez) were sufficiently convincing to
      warrant follow-up clinical trials. These data suggest that while well-documented
      BCS do have an impact on the research agenda, in general, additional rigor is
      needed during their compilation.

PMID- 12516039
TI  - Traditional Chinese medicine in the treatment of breast cancer.
AB  - The treatment of breast cancer involves multiple disciplines, and current
      recommendations are based on modern tenets of biology and pharmacology along with
      a growing body of evidence-based literature. Despite advances in screening,
      surgery, adjuvant radiation, and systemic therapy, as well as novel biologically
      targeted therapies, there are limitations to their benefits, especially in
      advanced disease. Complementary therapies including Oriental medicine have
      enjoyed a growing popularity as a less intensive and more "natural" approach to
      achieving health or improving quality of life. However, definitive literature in
      this area is scant and therefore has not been integrated into the mainstream
      medical community. Traditional Chinese medicine (TCM) may serve as a useful model
      for scientific inquiry since there is a standardized system of diagnostics and
      therapies, and this discipline is practiced worldwide. Still, the holistic and
      individualized nature of TCM presents challenges to rigorous clinical testing,
      and as a result, most published work in this field is in the form of anecdotal
      reports or uncontrolled series. Among the components of TCM, herbal or botanical
      agents possess complex biological activities that could affect many aspects of
      carcinogenesis such as cell growth and proliferation, apoptosis, host-tumor
      interactions, and immune function and differentiation. Despite a fairly extensive
      series of laboratory studies detailing many biological effects of botanical
      agents, few clinical trials have been completed to test specific hypotheses
      regarding the mode of action of TCM. Most TCM therapies have been empirically
      applied in a series of patients, with descriptive results provided. The summaries
      of a few studies highlighted in this review can provide some evidence of safety
      but generally do not possess the design and results to verify clinical
      effectiveness. Nevertheless, the theory of TCM coupled with laboratory studies
      and safety information can serve as a basis for the design of more definitive
      trials of TCM for specific indications in breast cancer. There are increasing
      interest and growing opportunities for investigative approaches that could
      ultimately verify or reject TCM and specific botanical agents. Some of these
      initiatives in the area of breast cancer prevention and treatment are outlined.

PMID- 12516040
TI  - Complementary and alternative therapies in prostate cancer.
AB  - Complementary and alternative therapies are used with increasing frequency in men
      with prostate cancer. However, little is known about the efficacy of such
      therapies for this cancer. While epidemiological data support the association
      between intake of certain micronutrients with development of prostate cancer,
      there exist limited prospective data that support the chemopreventative or
      therapeutic value of such nutritional agents in prostate cancer. To date, one of
      the most studied treatments has been PC-SPES, a combination of eight herbal
      therapies with activity against prostate cancer. Studies in cell lines of human
      prostate cancer demonstrate significant dose-dependent decreases in cellular
      viability after exposure to extracts of this agent. Clinical studies suggested
      that PC-SPES could reduce prostate specific antigen levels in patients with
      either androgen-dependent or androgen-independent prostate cancer. Toxicity was
      mild, although there was a low risk of thromboembolic events with such treatment.
      Manufacture of PC-SPES was recently halted, after revelations that the herbal
      combination was contaminated with warfarin, which led to a recall by the
      manufacturer. Subsequent analyses also revealed the presence of
      diethylstilbestrol (DES) and indomethacin in some lots of PC-SPES. Available data
      regarding other alternative therapies are reviewed as well.

PMID- 12516041
TI  - The Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center.
AB  - This article describes the development of the Integrative Medicine Service at
      Memorial Sloan-Kettering Cancer Center (MSKCC). It is hoped that our experience
      might be useful to others who are working to develop analogous programs in other
      centers.

PMID- 12516042
TI  - Mistletoe and cancer: controversies and perspectives.
AB  - Extracts and preparations from the tree parasitic plant mistletoe (Viscum album
      L.) have been used in the treatment of cancer for decades. Numerous preclinical
      and in vitro studies have reported immunostimulatory, cytotoxic, and proapoptotic
      effects. Translation of these effects into clinical response continues to pose a
      problem. While a number of clinical studies have found improvement in quality of
      life (QOL), data on the efficacy of mistletoe to prolong survival are conflicting
      and of variable quality. Clinical trial data regarding the toxicity and
      pharmacokinetics of mistletoe components with known in vitro or preclinical
      activity are lacking. Mistletoe is a widely used form of complementary and
      alternative medicine (CAM) for cancer treatment, and research into its use poses
      the challenges of translation of preclinical data into demonstrable clinical
      efficacy and investigating CAM approaches as a component of complex cancer
      treatment systems.

PMID- 12516043
TI  - Controversies in cancer and the mind: effects of psychosocial support.
AB  - In the last decades of the twentieth century, interest in effects of
      consciousness on health and illness generated several lines of investigation into
      effects on cancer. Animal studies showed sensitivity of some cancers to hormonal
      and stressful influences. However, those findings did not translate into effects
      on humans, nor did they lead to advances in understanding of human cancer. The
      proposal that emotional state or stress, mediated through psycho-neuro
      immunologic mechanisms would affect cancer generation or growth, resulted in
      conflicting information. Major surveys found no relationship. The proposal of a
      cancer personality (Type C) also was not confirmed. Initial observations that
      depression and stress affected human cancer seem to have best been explained by
      misinterpretations of cause and effect. By the mid 1990s, a remaining thesis-
      effect of psychosocial support on longevity and the course of cancer--was yet to
      be resolved. Initial positive results, especially findings in two popularly
      quoted studies, were not confirmed; they seem to have been due to inadequate
      numbers (chance) or to artifacts in study design or implementation. Psychosocial
      support may result in better adjustment and quality of life, but it does not
      directly affect the evolution of human cancer.

PMID- 12516044
TI  - Informed consent in complementary and alternative medicine: current status and
      future needs.
AB  - "Informed consent" is an action. It is a process that fulfills the pretreatment
      ethical obligations of provider to patient. Through the process, the provider
      discloses meaningful and realistic facts about positive and negative expectations
      concerning the proposed intervention and addresses concerns that are pertinent to
      the patient. Disclosure is of facts that are known or realistically expected to
      be known by a qualified provider regardless of background or product genus. The
      disclosure obligation does not vary with the background of the provider or the
      label given to the therapy. MD, nurse, naturapath, chiropractor, and licensed and
      unlicensed practitioner have the responsibility to provide quality information
      about the therapeutic worth of the intervention based on reliable data. This
      obligation pertains whether the intervention is standard, experimental,
      investigational, natural, alternative, complementary, or unproven.
      Misrepresentation of material facts voids consent and triggers legal liability.
      Today, the oncology community meets the informed consent obligation through a
      stepwise process that produces standards of care and builds studies and data
      collection to produce reliable outcome information on patient benefit. These data
      enrich the ability of a patient to consider and provide informed consent to
      treatment. In contrast, although there are some ongoing studies of complementary
      and alternative (CAM) therapies, there does not appear to be a groundswell of
      support for these activities within the CAM community. The development of
      standards of care and reliable information about CAM therapies appears to be
      seriously lagging and a disservice to obligations toward informed participation
      and consent by the patients seeking CAM interventions.

PMID- 12516046
TI  - A review of vaccines for HIV prevention.
AB  - HIV/AIDS has become the most devastating pandemic in recorded history. It has
      killed 40 million people in the last 20 years and the World Health Organisation
      estimated that at least 14,000 new infections occurred daily in 2001. There will
      be up to 100 million new infections in the next 10 years (for current updates,
      visit http://www.unaids.org/epidemic_update/). Most HIV infections occur in the
      developing world, and the adverse social and economic impact of the HIV/AIDS
      pandemic, particularly in the developing world, is unprecedented. Highly active
      antiretroviral therapy (HAART) has had significant effects on HIV/AIDS in the
      developed world. The drugs have acted to prolong survival, reduce the viral load,
      and to alleviate suffering. However, the incidence of side effects and resistance
      is high and the drugs are unaffordable and unavailable in the developing world.
      HAART regimens are difficult to comply with. Public health efforts to modify the
      behaviour, attitude and culture that accelerate the spread of HIV/AIDS have had
      only modest success. There is urgent need for a prophylactic and/or therapeutic
      HIV vaccine. This is a review of the obstacles and current trends in HIV vaccine
      development.

PMID- 12516047
TI  - Bone marrow stromal cells as a genetic platform for systemic delivery of
      therapeutic proteins in vivo: human factor IX model.
AB  - BACKGROUND: Hemophilia B is an X-linked bleeding disorder that results from a
      deficiency in functional coagulation factor IX (hFIX). In patients lacking FIX,
      the intrinsic coagulation pathway is disrupted leading to a lifelong,
      debilitating and sometimes fatal disease. METHODS: We have developed an ex vivo
      gene therapy system using genetically modified bone marrow stromal cells (BMSCs)
      as a platform for sustained delivery of therapeutic proteins into the general
      circulation. This model exploits the ability of BMSCs to form localized ectopic
      ossicles when transplanted in vivo. BMSCs were transduced with MFG-hFIX, a
      retroviral construct directing the expression of hFIX. The biological activity of
      hFIX expressed by these cells was assessed in vitro and in vivo. RESULTS:
      Transduced cells produced biologically active hFIX in vitro with a specific
      activity of 90% and expressed hFIX at levels of approximately 497 ng/10(6)
      cells/24 h and 322 ng/10(6) cells/24 h for human and porcine cells, respectively.
      The secretion of hFIX was confirmed by Western blot analysis of the conditioned
      medium using a hFIX-specific antibody. Transduced BMSCs (8 x 10(6) cells per
      animal) were transplanted within scaffolds into subcutaneous sites in
      immunocompromised mice. At 1 week post-implantation, serum samples contained hFIX
      at levels greater than 25 ng/ml. Circulating levels of hFIX gradually decreased
      to 11.5 ng/ml at 1 month post-implantation and declined to a stable level at 6.1
      ng/ml at 4 months. CONCLUSIONS: These findings demonstrate that genetically
      modified BMSCs can continuously secrete biologically active hFIX from self
      contained ectopic ossicles in vivo, and thus represent a novel delivery system
      for releasing therapeutic proteins into the circulation.

PMID- 12516048
TI  - Construction of a high efficiency retroviral vector for gene therapy of Hunter's
      syndrome.
AB  - BACKGROUND: As an alternative method to the conventional therapies for Hunter's
      syndrome, which is a lethal lysosomal storage disorder, we have developed gene
      delivery vehicles using a series of retroviral vectors. The objective of this
      study was to develop a safe and efficient retroviral vector and to optimize
      conditions for efficient transduction of human bone marrow CD34+ stem cells using
      our vector. METHODS: We constructed three types of MLV-based retroviral vectors
      expressing iduronate-2-sulfatase (IDS) which is deficient in patients suffering
      from Hunter's syndrome: MIN-IDS and MIM-IDS, which express IDS along with
      bacterial neo and human MDR genes, respectively, and MT-IDS lacking any
      selectable marker. Respective producer lines were derived from the packaging
      line, PG13, and compared for viral titer and levels of gene expression. After
      comparing, the retroviral vector, MT-IDS, was used to transduce human bone marrow
      CD34+ stem cells on fibronectin under various MOIs. RESULTS: In comparison, MT
      IDS not only produced the highest viral titer (close to 10(7) cfu/ml), but also
      showed the highest level of gene expression in various transduction assays and
      RNA analysis. When 1.5 x 10(5) human CD34+ bone marrow cells were transduced with
      MT-IDS under the most optimal MOIs, about 80% of total colony forming units were
      shown to contain the IDS cDNA. CONCLUSIONS: Minimum-sized retroviral vector that
      contains no selective marker as well as a viral coding sequences could drive a
      high level of gene expression, be produced efficiently from the producer line,
      and enter hematopoietic cells at a high frequency. Our data suggest the great
      potential for using MT-based vector(s) in a gene therapy trial for Hunter's
      syndrome utilizing human CD34+ stem cells as target cells.

PMID- 12516049
TI  - Gene therapy for prostate cancer using the cytosine deaminase/uracil
      phosphoribosyltransferase suicide system.
AB  - BACKGROUND: Cytosine deaminase (CD) activates prodrug 5-FC to 5-FU and is used
      for suicide gene therapy (the CD/5-FC system). E. coli uracil
      phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that directly
      converts 5-FU into 5-fluorouridine monophosphate and improves the antitumoral
      effect of 5-FU. This study demonstrates the effectiveness of transduction of the
      UPRT gene in addition to CD/5-FC cancer suicide gene therapy. METHODS: We
      investigated a combined suicide gene transduction therapy for human hormone
      independent prostate cancer cell line DU145 using two separate adenovirus vectors
      expressing the E. coli CD and E. coli UPRT genes and systemic 5-FC administration
      (the CD+UPRT/5-FC system). RESULTS: Cells transfected with AdCA-UPRT showed
      approximately 57 times lower IC50 to 5-FU compared with those transfected with
      AdCA-LacZ. Furthermore, cells transfected with AdCA-CD and AdCA-UPRT proved to be
      more sensitive to 5-FC compared with those transfected with AdCA-CD. Intratumoral
      injection of AdCA-CD and AdCA-UPRT drastically suppressed the growth of tumors
      which had generated from DU145 cells inoculated into athymic (nude) mice compared
      with those injected with AdCA-LacZ or AdCA-LacZ and AdCA-CD. CONCLUSIONS: These
      results suggest that the CD+UPRT/5-FC system could be a powerful factor in human
      prostate cancer suicide gene therapy.

PMID- 12516050
TI  - Uptake of plasmid/glycosylated polymer complexes and gene transfer efficiency in
      differentiated airway epithelial cells.
AB  - BACKGROUND: We have studied gene transfer efficiency of glycosylated polylysines
      and glycosylated polyethylenimines as vectors in immortalized differentiated
      airway gland serous cells and primary cultures of human airway surface epithelial
      cells. METHODS AND RESULTS: In both cell types, lactosylated PEI was more
      efficient for gene transfer than unsubstituted PEI and lactosylated polylysine
      which requires the presence of endosomolytic agents. However, for all the vectors
      tested, gene transfer efficiency was lower in differentiated cells as compared
      with poorly differentiated cells. The presence of membrane lectins, i.e. cell
      surface sugar-specific receptors, was evaluated using fluorescein-conjugated
      neoglycoproteins and microscopy or flow cytometry. In differentiated airway
      surface epithelial cells, membrane lectins were not expressed and plasmid
      DNA/fluorescein-conjugated glycosylated polymer complexes were not incorporated.
      This accounted in part for the lack of gene transfer efficiency in these cells.
      In contrast, in differentiated airway gland serous cells, expression of lectins
      and their endocytotic properties appeared to be similar to that observed in
      undifferentiated cells, and plasmid DNA/fluorescein-conjugated glycosylated
      polymer complexes were incorporated in similar amounts by cells in both
      differentiated states CONCLUSIONS: Glycosylated PEI appears to be a promising
      gene delivery system since it is more efficient than the sugar-free polymer and
      does not require endosomolytic agents. However, in differentiated airway gland
      serous cells, a low gene transfer efficiency was observed that could not be
      attributed to low expression of membrane lectins or low uptake of glycosylated
      complexes. An impaired intracellular trafficking of glycosylated complexes in
      differentiated airway gland serous cells is suggested.

PMID- 12516051
TI  - Interaction of bronchoalveolar lavage fluid with polyplexes and lipoplexes:
      analysing the role of proteins and glycoproteins.
AB  - BACKGROUND: Plasmid DNA complexed with cationic lipids (lipoplexes) or cationic
      polymers (polyplexes) has been used for gene transfer into the lung. Topical gene
      administration of lipoplexes or polyplexes into the lung after intratracheal
      instillation or aerosolisation could cause interaction of the complexes with
      extracellular substances of the airway surface liquid (ASL). These extracellular
      interactions might be causal for the observed inefficient transfection rate in
      vivo after topical administration. Therefore, we studied the impact of
      bronchoalveolar lavage fluid (BALF) on reporter gene expression mediated by non
      viral gene vectors. BALF was considered as a model system to mimic possible
      interactions of the gene vectors with the ASL. METHODS: BALF was taken from 15
      patients who underwent diagnostic bronchoscopy. Lipoplexes and polyplexes were
      incubated with increasing concentrations of BALF and major components of the BALF
      such as albumin, mucin and alpha(1)-glycoprotein, as a representative of
      glycosylated proteins. As cationic polymers, we tested dendrimers (fractured
      PAMAM) and polyethylenimine 25 kDa (PEI) and, as cationic liposomes, we used
      Lipofect-AMINE. The effect of BALF on polyplexes and lipoplexes was analysed by
      transfection experiments, fluorescence-quenching assay, 2-D-gel electrophoresis,
      SDS-PAGE, DNAse protection assay, size and zeta-potential measurements. RESULTS:
      BALF inhibited polyplex- and lipoplex-mediated gene transfer. Analysing
      components of BALF, we found that dendrimer-mediated gene transfer was not
      inhibited by any specific component. PEI-mediated gene transfer was dose
      dependently inhibited by alpha(1)-glycoprotein, slightly inhibited by mucin, but
      not inhibited in the presence of albumin. Lipoplex-mediated gene transfer was
      inhibited by mucin at higher concentrations and by albumin, but not by alpha(1)
      glycoprotein. 2-D-gel electrophoresis revealed that proteins of the BALF were
      adsorbed more intensively to lipoplexes than to polyplexes. In addition, mucin
      and alpha(1)-glycoprotein also adsorbed more intensively to lipoplexes than to
      polyplexes. Adsorption of BALF components led to a decrease in the positive zeta
      potential of lipoplexes and led to a negative zeta-potential of polyplexes.
      Complement cleavage fragment C3 beta, and in the case of lipoplexes also the C3
      alpha fragment, were found among the proteins opsonised on gene vectors.
      CONCLUSIONS: Our study shows that BALF contains inhibitory components for non
      viral gene transfer. We could not detect a specific inhibitory component, but
      inhibition was most likely due to the change in the surface charge of the gene
      vectors. Interestingly, there is evidence for complement activation when the
      route of pulmonary gene vector administration is chosen. Consequently, shielding
      of gene vectors to circumvent interaction with the ASL environment should be a
      focus for pulmonary administration in the future.

PMID- 12516052
TI  - Optimisation of dendrimer-mediated gene transfer by anionic oligomers.
AB  - BACKGROUND: The application of synthetic vectors for gene transfer has potential
      advantages over virus-based systems. Their use, however, is limited since they
      generally lack the efficiency of gene transfer achieved with recombinant viral
      vectors such as adenovirus. Polyamidoamine (PAMAM) and phosphorus-containing
      dendrimers (P-dendrimers) are specific polymers with a defined spherical
      structure. They bind to DNA through electrostatic interactions thus forming
      complexes that efficiently transfect cells in vitro. METHODS AND RESULTS: The
      influence of anionic oligomers (oligonucleotides, dextran sulfate) on dendrimer
      mediated polyfection of cultured cells has been studied. Anionic oligomers have
      been found to increase significantly the capacity of the PAMAM and P-dendrimers
      for DNA delivery into cells when they were mixed with plasmid DNA before addition
      of dendrimers. The efficiency of the DNA/dendrimer penetration depends on the
      size, structure and charge of anionic oligomers. CONCLUSIONS: Our results
      represent an important step towards the optimisation of gene transfer mediated by
      two types of dendrimers. The use of anionic oligomers improves the efficiency of
      gene expression within cells. As a consequence, a very efficient cell polyfection
      can be achieved with a lower plasmid quantity for the PAMAM dendrimer greatly
      increasing the gene expression level for P-dendrimers.

PMID- 12516053
TI  - Upregulation of expression from the FRDA genomic locus for the therapy of
      Friedreich ataxia.
AB  - BACKGROUND: Friedreich ataxia is a slowly progressive neurodegenerative disease
      caused by reduced expression of frataxin as a result of a GAA repeat expansion in
      the first intron of the FRDA gene. We report here the development of a sensitive
      cellular assay for frataxin expression from the intact FRDA locus that should
      facilitate the identification of potentially therapeutic pharmacological agents
      to treat Friedreich ataxia. METHODS: PAC and BAC clones containing the entire
      human FRDA functional genomic sequence were identified and shown to express FRDA
      mRNA. The GET Recombination system was used to insert cassettes consisting of the
      gene encoding EGFP linked to a kanamycin/neomycin resistance determinant into a
      BAC clone containing the entire FRDA gene and surrounding regions. RESULTS: Two
      in-frame fusions between the FRDA gene and a gene coding for enhanced green
      fluorescent protein (EGFP) were constructed. One fusion is within exon 2 of the
      FRDA gene. The other is at the end of exon 5a, containing the entire frataxin
      protein fused to EGFP. Both constructs were shown to drive the expression of EGFP
      from the regulatory elements of the FRDA locus, with the frataxin-EGFP fusion
      proteins targeted to the mitochondria. Stable cell lines containing the EGFP
      fusion in exon 5a were produced. Enhancement of FRDA gene expression by hemin and
      butyric acid was demonstrated. CONCLUSIONS: Expression studies with FRDA-EGFP
      fusion constructs will facilitate delineation of regulatory elements determining
      the tissue and developmental specificity of FRDA gene expression. These
      constructs should also facilitate screening for pharmacological compounds that
      can modulate the expression of the FRDA gene in a clinically relevant manner.

PMID- 12516054
TI  - French gene therapy group reports on the adverse event in a clinical trial of
      gene therapy for X-linked severe combined immune deficiency (X-SCID). Position
      statement from the European Society of Gene Therapy.

PMID- 12516055
TI  - The Journal of Gene Medicine 2002 Young Investigator Award. European Society of
      Gene Therapy.

PMID- 12516056
TI  - The Journal of Gene Medicine 2002 Young Investigator Award. Japan Society of Gene
      Therapy.

PMID- 12516057
TI  - The indirect effects of virus infections.

PMID- 12516058
TI  - The new cell culture smallpox vaccine should be offered to the general
      population.
AB  - A series of major factors must be weighed in deciding whether or not, and to what
      extent, a particular country should consider pre-exposure vaccination for
      smallpox. These include the risk of a bioterrorist attack using smallpox, the
      risk of secondary spread from another country, the risks and benefits of
      vaccination, the effectivenes s of vaccination pre- and post-exposure, the
      prevalence of immunocompromised persons, the capacity of the medical care
      delivery system and the wealth of a nation. We review here the issues and
      variables relevant for policy making, propose a framework for country-specific
      decision making and suggest the World Health Organization has a key role to play,
      particularly with regard to lower-income countries. In doing so, we support the
      proposition.

PMID- 12516059
TI  - The new cell culture smallpox vaccine should not be offered to the general
      population.
AB  - Cell based smallpox vaccines are to be welcomed, but any decision to vaccinate
      whole populations must await firstly better intelligence about the gravity of the
      threat from bioterrorists, including their ability to release smallpox in such a
      way that wide dissemination could take place; secondly evidence that vaccines
      grown in cell culture are protective and safe; and thirdly that the vaccines
      would be generally acceptable and their introduction would not compromise the
      rest of national immunisation programmes. Smallpox vaccination should not be
      offered to the general population until these uncertainties have been resolved,
      by which time bioterrorism might possibly have been overcome or the development
      of antiviral treatment might have made renewed smallpox vaccination unnecessary.
      Meanwhile, preparations for rapid deployment of the historically well-tried
      containment measures at the epicentres of any smallpox release should proceed,
      their effectiveness should be tested, and their adequacy kept under review.

PMID- 12516060
TI  - Viral induction of site-specific chromosome damage.
AB  - The advent of advanced cell culture and cytogenetics techniques in the 1950s
      opened a new avenue for research on the pathogenic interactions between animal
      viruses and their hosts. Studies of many viruses revealed their ability to
      nonspecifically induce cytogenetic damage to their host cell's chromosomes.
      However, only three viruses, the oncogenic adenoviruses, herpes simplex virus
      (HSV) and human cytomegalovirus (HCMV), have been found to cause non-random, site
      specific chromosomal damage. Adenovirus (Ad) type 12 induces fragility at four
      distinct loci (RNU1, RNU2, RN5S and PSU1) in many different types of human cells.
      A common feature of these loci is that they contain a repeated array of
      transcriptionally active genes encoding small structural RNAs. Site-specific
      induction of breaks also requires the virally encoded E1B protein of M(r) 55000
      and the C-terminus of the cellular p53 protein. Analysis of the induction of
      damage by HSV and HCMV necessitates consideration of several factors, including
      the strain of virus used, the timing of infection, the type of cell used, and the
      multiplicity of infection. Both HSV strains 1 and 2 are cytotoxic, although the
      former seems to be more proficient at inducing damage. At early times post
      infection, HSV induces breaks and specific uncoiling of the centromeres of
      chromosomes 1, 9 and 16. This is followed at later times by a more complete
      severing of all of the chromosomes, termed pulverisation. Damage by HSV requires
      viral entry and de novo viral protein synthesis, with immediate early viral
      proteins responsible for the induction of breaks and uncoiling and early gene
      products (most likely nucleases) involved in the extensive pulverisation seen
      later. HCMV has been studied primarily in permissive human fibroblasts. Its
      ability to induce specific damage in chromosome 1 at two loci, 1q21 and 1q42, was
      only recently revealed as the cells must be in S-phase when they are infected for
      the breaks to be observed. In contrast to adenovirus and HSV, HCMV induction of
      specific breakage requires only viral entry into the cell and not de novo viral
      protein expression. This latter point may be a factor in its ability to cause
      damage in the developing fetal brain, where the most severe clinical
      manifestations of congenital infection are observed.

PMID- 12516061
TI  - The influence of cytokines, chemokines and their receptors on HIV-1 replication
      in monocytes and macrophages.
AB  - Monocytes, macrophages and dendritic cells play an important role in the initial
      infection and contribute to its pathogenesis throughout the course of infection.
      Myeloid cells express CD4 and chemokine receptors known for HIV-1 fusion and
      entry. The beta-chemokine receptor, CCR5, is the major co-receptor in conjunction
      with CD4 for macrophage (M)-tropic or (R5) isolates of HIV-1, whereas the alpha
      chemokine receptor, CXCR4, facilitates entry of T-tropic or (X4) HIV-1 strains.
      Cells of myeloid lineage may be infected predominantly with R5- strains, although
      infection with dual-tropic isolates of HIV-1 (exhibiting the capacity to use CCR
      5 and/or CXCR-4 for entry) or some strains of X4- isolates has also been
      reported. The expression of chemokine receptors, HIV-1 infection and replication
      is under continuous regulation by a complex cytokine network produced by a
      variety of cells. The effects of cytokines/chemokines on HIV-1 replication in
      cells of myeloid lineage can be inhibitory (IFN-alpha, IFN-beta, IFN-gamma, GM
      CSF, IL-10, IL-13 and IL-16 and beta-chemokines), stimulatory (M-CSF, TNF-alpha,
      TNF-beta, IL-1, IL-6) or bifunction al, that is both inhibitory and stimulatory
      (IL-4). This review focuses on the overall expression of chemokine receptors on
      cells of myeloid lineage and considers the mechanisms of entry of R5-, X4- and
      dual-tropic strains of HIV-1 into these cells. The effects of
      cytokines/chemokines on viral entry and productive HIV-1 infection are also
      reviewed.

PMID- 12516062
TI  - Clinical consequences of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is a positive strand RNA virus that belongs to the
      Hepacivirinae genus within the Flaviviridae family. HCV infection has a wide
      spectrum of cellular tropism and clinical presentations. This has major impacts
      in terms of pathogenesis and diagnosis. Consequently, a wide range of clinical
      consequences characterises this viral infection, including asymptomatic chronic
      carriage, acute hepatitis, chronic hepatitis, cirrhosis, hepatocellular carcinoma
      and extrahepatic manifestations. The latter are commonly observed and may
      represent the first sign of the disease. A better knowledge of the pathobiology
      of HCV and its clinical consequences will be important for developing better
      treatment strategies to cure HCV infection and extrahepatic manifestations.

PMID- 12516063
TI  - Modulated low-energy near-infrared (NIR) lasers and cancer: an invitation to
      discuss a new treatment approach.

PMID- 12516064
TI  - Quantitative assessment of chondrocyte viability after laser mediated reshaping:
      a novel application of flow cytometry.
AB  - BACKGROUND AND OBJECTIVES: Lasers can be used to reshape cartilage by
      accelerating mechanical stress relaxation. In this study, fluorescent
      differential cell viability staining and flow cytometry were used to determine
      chondrocyte viability following laser heating. STUDY DESIGN/MATERIALS AND
      METHODS: Porcine septal cartilages were irradiated with an Nd:YAG laser (lambda =
      1.32 microm, 25 W/cm(2)) while surface temperature, stress relaxation, and
      diffuse reflectance were recorded. Each slab received one, two, or three laser
      exposures (respective exposure times of 6.7, 7.2, 10 seconds). Irradiated samples
      were then divided into two groups analyzed immediately and at 5 days following
      laser exposure. Chondrocytes were isolated following serial enzymatic digestion,
      and stained using SYTO/DEAD Red (Molecular Probes, Eugene, OR). A flow cytometer
      was then used to detect differential cell fluorescence; size; granularity; and
      the number of live cells, dead cells, and post-irradiation debris in each
      treatment population. RESULTS: Nearly 60% of chondrocytes from reshaped cartilage
      samples isolated shortly after one irradiation, were viable while non-irradiated
      controls were 100% viable. Specimens irradiated two or three times demonstrated
      increasing amounts of cellular debris along with a reduction in chondrocyte
      viability: 31 and 16% after two and three exposures, respectively. In those
      samples maintained in culture medium and assayed 5 days after irradiation,
      viability was reduced by 28-88%, with the least amount of deterioration in
      untreated and singly irradiated samples. CONCLUSIONS: Functional fluorescent dyes
      combined with flow cytometric analysis successfully determines the effect of
      laser irradiation on the viability of reshaped cartilage.

PMID- 12516065
TI  - Temporally and spectrally resolved fluorescence spectroscopy for the detection of
      high grade dysplasia in Barrett's esophagus.
AB  - BACKGROUND AND OBJECTIVES: Temporal and spectral fluorescence spectroscopy can
      identify adenomatous colonic polyps accurately. In this study, these techniques
      were examined as a potential means of improving the surveillance of high grade
      dysplasia (HGD) in Barrett's esophagus (BE). STUDY DESIGN/MATERIALS AND METHODS:
      Using excitation wavelengths of 337 and 400 nm, 148 fluorescence spectra, and 108
      transient decay profiles (at 550 +/- 20 nm) were obtained endoscopically in 37
      patients. Corresponding biopsies were collected and classified as carcinoma, HGD,
      or low risk tissue (LRT) [non-dysplastic BE, indefinite for dysplasia (IFD), and
      low grade dysplasia (LGD)]. Diagnostic algorithms were developed retrospectively
      using linear discriminant analysis (LDA) to separate LRT from HGD. RESULTS: LDA
      produced diagnostic algorithms based solely on spectral data. Moderate levels of
      sensitivity (Se) and specificity (Sp) were obtained for both 337 nm (Se = 74%, Sp
      = 67%) and 400 nm (Se = 74%, Sp = 85%) excitation. CONCLUSIONS: In the diagnosis
      of HGD in BE, steady-state fluorescence was more effective than time-resolved
      data, and excitation at 400 nm excitation was more effective than 337 nm. While
      fluorescence-targeted biopsy is approaching clinical usefulness, increased
      sensitivity to dysplastic changes-possibly through modification of system
      parameters-is needed to improve accuracy levels.

PMID- 12516066
TI  - Detection and diagnosis of oral cancer by light-induced fluorescence.
AB  - BACKGROUND AND OBJECTIVE: New techniques for non-invasive early detection and
      diagnosis of oral dysplasia and carcinoma are required. Our objective was to
      determine in the hamster cheek pouch model whether differentiation between the
      healthy tissue and the different stages of oral premalignancy and malignancy is
      possible using laser-induced fluorescence after tissue exposure to 5
      Aminolevulinic acid (ALA). STUDY DESIGN/MATERIALS AND METHODS: DMBA
      carcinogenesis was applied to one cheek pouch in 18 hamsters for 0-20 weeks.
      Prior to sacrifice, 20% ALA was applied to the cheek tissues. Excised cheek
      tissues were cryosectioned and imaged using fluorescence microscopy with
      excitation at 405 nm, detection at 635 nm. After fluorescence measurement, H&E
      staining and histopathological evaluation were performed. RESULTS: Fluorescence
      intensity was significantly lower in healthy tissue than in pathological tissues.
      Significantly higher intensities and more "fluorescence hot spots" occurred in
      severe dysplasia and carcinoma than in healthy tissue, hyperkeratosis, mild and
      moderate dysplasia. CONCLUSIONS: Light-induced fluorescence after ALA exposure
      can differentiate between the different stages of premalignancy and malignancy.
      Its ability to differentiate between healthy tissue and early pathology is
      particularly interesting

PMID- 12516067
TI  - Basic study on vibrations during tooth preparations caused by high-speed drilling
      and Er:YAG laser irradiation.
AB  - BACKGROUND AND OBJECTIVES: An Er:YAG laser effectively removes dental hard
      substance, and causes less pain during tooth preparations than high-speed
      drilling. This laser was introduced to eliminate the noise, vibration, pressure,
      and heat associated with the high-speed drilling. However, the difference in
      tooth vibration caused by the Er:YAG laser and the high-speed drill is unclear.
      Therefore, the aim of this study was to evaluate tooth vibration obtained with
      the Er:YAG laser and high-speed drill. STUDY DESIGN/MATERIALS AND METHODS: Each
      of the five extracted permanent upper first premolars were built up in a plaster
      box. In this study, a silicone impression material was selected to simulate
      periodontal tissue. The vibration speed was measured by using a laser Doppler
      vibrometer. RESULTS: The Er:YAG laser irradiation energy was 50, 100, 145, 199,
      300, and 350 mJ. As irradiation energy increased, vibration of the tooth also
      rose; a high-correlation coefficient was observed between them. We found that
      only a small amount of the tooth vibration occurred with the Er:YAG laser
      preparations. The mean vibration speed and standard deviation with the laser were
      166 +/- 28 microm/second when the output energy was 145 mJ, whereas those with
      the high-speed drill were 65 +/- 48 mm/second. The frequency characteristic
      approached 230 Hz and 5 kHz, respectively. CONCLUSIONS: These results show that
      the high-speed drilling causes greater tooth vibration and has a frequency
      spectrum near the high sensitivity of hearing compared to the Er:YAG laser. This
      suggests a potential factor in provoking pain and displeasure during tooth
      preparation. Future study to examine the relationship of pain and amount of tooth
      vibration will be planned.

PMID- 12516068
TI  - Chronic and acute analysis of optic nerve sheath fenestration with the free
      electron laser in monkeys.
AB  - BACKGROUND AND OBJECTIVES: The Amide II wavelength (6.45 microm) produced by the
      free electron laser (FEL) can efficiently create an optic nerve sheath
      fenestration in rabbits. We wished to determine if it would be equally successful
      in macaque monkeys and to determine the histopathologic changes between
      traditional scissors or knife optic nerve sheath fenestration to FEL
      fenestration. STUDY DESIGN/MATERIALS AND METHODS: Optic nerve sheath fenestration
      was performed using either the FEL (6.45 microm, 30 Hz, 2-3 mJ, 325-microm spot
      size) through a hollow waveguide probe in 12 eyes or with a scissors or a knife
      in 6 eyes. The monkeys survived 1 month with the fellow optic nerve operated
      acutely just prior to sacrifice. Optic nerves were evaluated histologically.
      RESULTS: Less tissue manipulation was required using the FEL surgical probe.
      Electroretinograms showed minimal or no change. Tissue responses using either
      method were similar following chronic or acute incisions. Mild upregulation of
      vimentin and glial fibrillary acid protein (GFAP) was seen in astrocytes adjacent
      to the fenestration, but no change in S100 beta was evident. CONCLUSIONS: The FEL
      energy at 6.45 microm delivered through a hollow waveguide appears capable of
      efficiently and safely producing an optic nerve sheath fenestration in monkeys.
      This innovative surgical technique should be considered for human use.

PMID- 12516069
TI  - Prospective study on the treatment of postburn hyperpigmentation by intense
      pulsed light.
AB  - BACKGROUND AND OBJECTIVES: Postburn hyperpigmentation is a common phenomenon
      among Asian especially over grafted areas and sometimes over donor sites and
      healed wounds without skin graft. This condition is difficult to treat and can
      cause severe psychological distress. Intense pulsed light (IPL) has been used to
      treat melanocytic lesions with promising result. The role of IPL in treating
      postburn hyperpigmentation has not been explored. The purpose of this study was
      to assess the efficacy and complication of IPL in the treatment of postburn
      hyperpigmentation prospectively. STUDY DESIGN/MATERIALS AND METHODS: Nineteen
      Chinese patients with postburn hyperpigmentation were treated by IPL. There were
      14 females and 5 males. Their age ranged from 8 to 51 years with a mean age of
      29.4 +/- 11.6 years. The cutoff filters of 550, 570, and 590 nm were used for 3-7
      treatments at intervals of 3-4 weeks. Patients were treated with an energy
      fluence of 28-46 J/cm(2), pulse width of 1.7-4 milliseconds, double pulse mode,
      and a delay of 15-40 milliseconds. RESULTS: Treatment results and complications
      were evaluated and scored after each treatment. Over 78% of the patients showed
      more than 50% clinical clearance and nearly 32% of the patients were able to
      achieve more than 75% clearing. Although two patients had no clinical response,
      one patient had 100% clearing. Three patients developed blisters and one patient
      had erythema that all resolved within 1 week without leaving permanent marks.
      They have been followed-up from 11-32 months and there was no recurrence of the
      hyperpigmentation. CONCLUSIONS: IPL is effective and safe in treating postburn
      hyperpigmentation in Asian patients.

PMID- 12516070
TI  - Ultrastructural changes elicited by a non-ablative wrinkle reduction laser.
AB  - BACKGROUND AND OBJECTIVES: Cosmeceuticals, chemical peels and collagen injections
      are used to rejuvenate skin, but none of these methods is effective or permanent.
      Recently, laser resurfacing has been found to be effective, but the incidence of
      side effects is relatively high. Two years ago, the non-ablative wrinkle
      reduction laser (N-Lite, ICN Photonics, UK) was developed, and there have been
      several reports about its clinical effectiveness. In this study, we have
      investigated ultrastructural changes elicited by exposure to the N-Lite laser.
      STUDY DESIGN/MATERIALS AND METHODS: Eight adult volunteers were recruited for
      this study. They were treated with the N-Lite laser and 3-mm skin punch biopsies
      were obtained 3 hours, 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks after
      the laser exposure. These specimens were examined by electron microscopy.
      RESULTS: Three hours after the laser therapy, the capillaries showed endothelial
      cell edema with hemostasis and marked edema was observed around them.
      Neutrophils, monocytes and mast cells were observed in the extravascular dermis.
      These acute dermal inflammatory changes were observed until 1 week after the
      laser treatment. Two weeks after the laser treatment, the capillaries showed an
      almost normal structure, and dermal edema was not observed around them. New
      elastic fibers and collagen fibers had increased around the capillaries. Four
      weeks after the laser treatment, interstitial fibrosis was observed around the
      capillaries. CONCLUSIONS: N-Lite laser irradiation leads to interstitial
      fibrosis, especially around the capillaries, 4 weeks after the laser irradiation.

PMID- 12516071
TI  - Spectral response for laser enhancement in hepatic regeneration for
      hepatectomized rats.
AB  - BACKGROUND AND OBJECTIVES: The low intensity laser therapy (LILT) has been widely
      used in all medical fields due to its therapeutic effects in reparative process,
      pain relief, and biostimulation. Even though there is a therapeutic window of
      wavelengths for clinical application, little has been done concerning the
      frequency spectrum response to biological effects. In this work, we investigate
      the dependence of different wavelengths irradiation in the enhancement of the
      tissue regeneration after partial hepatectomy in Wistar rats. STUDY
      DESIGN/MATERIALS AND METHODS: The proliferating cell nuclear antigen (PCNA)
      labeling index and the respiratory control (oxygen consumption in extracted
      mitochondria) were the tests used to evaluate the liver regeneration after laser
      irradiation with different wavelengths. RESULTS AND CONCLUSIONS: The results show
      a correlated spectral response that can be explained based on the combined effect
      of light penetration on biological tissues and the biomolecular excitation
      efficiency for each wavelength used.

PMID- 12516072
TI  - MRI thermodosimetry in laser-induced interstitial thermotherapy.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to establish a correlation
      between a thermal measurement and a magnetic resonance imaging (MRI) signal
      during laser-induced interstitial thermotherapy (LITT) in liver. STUDY
      DESIGN/MATERIALS AND METHODS: Pig liver was irradiated for 15 minutes with a
      diode laser at two different powers, 0.5 W (450 J) and 1.5 W (1,350 J). Tissue
      temperature was monitored every 20 seconds using thermocouples. Thermosensitive
      MRI sequences (T(1)-weighted Turbo-Flash) were acquired with the same irradiation
      parameters. Correlation between MRI signals (SI) and temperature measures was
      defined at two different distances from the fiber (5 and 10 mm). RESULTS: At 0.5
      W, temperatures rose progressively up to a maximum increase of 9.5 degrees C at 5
      mm and 4 degrees C at 10 mm after 15 minutes. The corresponding MRI signal
      decreased progressively to -27.6 SI at 5 mm and -18.5 SI at 10 mm. At 1.5 W,
      temperatures rose dramatically at 5 mm, reaching a plateau. The temperature
      elevation measured at the end of the irradiation was of 30 degrees C whereas at
      10 mm it was only 14.5 degrees C. The MRI signal varied accordingly, remaining
      inversely proportional to temperature (-76 SI at 5 mm and -35.5 SI at 10 mm).
      CONCLUSIONS: An inversely proportional relationship was observed between MRI
      signal in sequential Turbo-Flash and temperature. MRI should allow to analyze
      heat diffusion in the liver, and thus to monitor real-time LITT treatments.

PMID- 12516073
TI  - Experimental photodynamic therapy for malignant pleural mesothelioma with
      pegylated mTHPC.
AB  - BACKGROUND AND OBJECTIVES: Experimental assessment of photodynamic therapy (PDT)
      for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta
      tetrahydroxyphenylchlorin (PEG-mTHPC). STUDY DESIGN/MATERIALS AND METHODS: (a)
      PDT was tested on H-meso-1 xenografts (652 nm laser light; fluence 10 J/cm(2);
      0.93, 9.3, or 27.8 mg/kg of PEG-mTHPC; drug-light intervals 3-8 days). (b)
      Intraoperative PDT with similar treatment conditions was performed in the chest
      cavity of minipigs (n = 18) following extrapleural pneumonectomy (EPP) using an
      optical integrating balloon device combined with in situ light dosimetry.
      RESULTS: (a) PDT using PEG-mTHPC resulted in larger extent of tumor necrosis than
      in untreated tumors (P < or = 0.01) without causing damage to normal tissue. (b)
      Intraoperative PDT following EPP was well tolerated in 17 of 18 animals. Mean
      fluence and fluence rates measured at four sites of the chest cavity ranged from
      10.2 +/- 0.2 to 13.2 +/- 2.3 J/cm(2) and 5.5 +/- 1.2 to 7.9 +/- 1.7 mW/cm(2)
      (mean +/- SD). Histology 3 months after light delivery revealed no PDT related
      tissue injury in all but one animal. CONCLUSIONS: PEG-mTHPC mediated PDT showed
      selective destruction of mesothelioma xenografts without causing damage to
      intrathoracic organs in pigs at similar treatment conditions. The light delivery
      system afforded regular light distribution to different parts of the chest
      cavity.

PMID- 12516074
TI  - Evaluation of a novel method to estimate absolute bioavailability of drugs from
      oral data.
AB  - The goal of this investigation was to evaluate the performance of a novel method
      allowing estimation of absolute bioavailability from oral data only. In contrast
      to the traditional method, which compares areas under the drug concentration time
      curves after oral and intravenous administration in subjects with normal renal
      function, the novel method uses total and renal clearance values following oral
      administration from subjects with varying renal functions to estimate
      bioavailability. The novel method can also provide estimates for nonrenal
      clearance.Published data on total clearance and renal clearance of drugs obtained
      from subjects with variable renal functions were collected, the novel method
      applied, estimates of bioavailability and nonrenal clearance obtained and
      compared with reported estimates by the traditional methods. In addition
      computations were performed to assess various factors that could possibly affect
      the reliability of the novel method. The results indicated that the novel method
      provides accurate estimates for bioavailability of drugs meeting the
      prerequisites: linear kinetics, predominant renal excretion in normals, absence
      of metabolic polymorphism and independence of bioavailability and nonrenal
      clearance from renal function. The average (standard deviation) of the prediction
      error and bias of the bioavailability estimates by the novel method was 7.8 (6.0)
      and -1.4 (9.8)%, respectively. The estimates for nonrenal clearance by the novel
      method were less accurate. The computations confirmed that the estimates by the
      novel method are sensitive to renal-function dependent changes in nonrenal
      clearance and bioavailability and also depend on the extent of renal excretion of
      a drug. In conclusion, the novel method's main use is to diagnose absence or
      presence of changes in bioavailability and non-renal clearance of drugs in
      populations with varying renal function.

PMID- 12516075
TI  - Enhancement of in vitro and in vivo microdialysis recovery of SB-265123 using
      Intralipid and Encapsin as perfusates.
AB  - This study was conducted to compare the ability of two potential microdialysis
      perfusates to enhance the recovery of SB-265123, a lipophilic, highly protein
      bound compound, both in vitro and in vivo. Initial in vitro experiments
      established that the recovery of SB-265123 by microdialysis using normal saline
      as a perfusate was poor (1.7%). Different concentrations of Intralipid and
      Encapsin also were evaluated in an identical in vitro setting, to determine
      enhancement of recovery. In vitro recovery was enhanced to approximately 24 and
      65% with 5 and 20% Intralipid, and to approximately 59 and 62% with 5 and 20%
      Encapsin, respectively. A rat in vivo study was conducted with 20% Encapsin to
      confirm the in vitro observations. In the in vivo study, 75-80% recovery of free
      SB-265123 was achieved using 20% Encapsin as a perfusate. The results from this
      study indicate that for SB-265123, a lipophilic, highly protein-bound molecule,
      Encapsin is an efficient recovery enhancer in vitro. The results from this
      investigation further demonstrate that a recovery enhancer may be useful for in
      vivo applications, even with a compound that is highly bound to plasma protein.

PMID- 12516076
TI  - Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant Nagase
      analbuminemic rats.
AB  - The importance of plasma protein binding of intravenous furosemide in circulating
      blood for its urinary excretion and hence its diuretic effects in mutant Nagase
      analbuminemic rats (NARs, an animal model for human familial analbuminemia) was
      reported. Based on the furosemide report, the diuretic effects of another loop
      diuretic, torasemide, could be expected in NARs if plasma protein binding of
      torasemide is considerable in the rats. This was proven by this study. After
      intravenous administration of torasemide, 10 mg/kg, to NARs, the plasma protein
      binding of torasemide was 23.3% in the rats due to binding to alpha- and beta
      globulins (this value, 23.3%, was greater than only 12% for furosemide), and
      hence the percentages of intravenous dose of torasemide excreted in 8-h urine as
      unchanged drug was 14.9% in the rat (this value was considerably greater than
      only 7% for furosemide). After intravenous administration of torasemide to NARs,
      the AUC (301 versus 2680 microg/min/ml) was significantly smaller [due to
      significantly faster both Cl(r) (4.81 versus 0.386 ml/min/kg) and Cl(nr) (28.3
      versus 3.33 ml/min/kg)], terminal half-life (18.3 versus 73.5 min) and mean
      residence time (6.97 versus 61.8 min) were significantly shorter (due to faster
      Cl, 33.2 versus 3.74 ml/min/kg), and amount of 8-h urinary excretion of unchanged
      torasemide (446 versus 323 microg, due to increase in intrinsic renal excretion)
      was significantly greater than those in control rats. The 8-h urine output and 8
      h urinary excretions of sodium and chloride were comparable between two groups of
      rats although the 8-h urinary excretion of torasemide was significantly greater
      in NARs. This could be explained by the following. The amount of urinary
      excretion of torasemide was significantly greater in NARs than that in control
      rats only between 0 and 30 min urine collection. In both groups of rats, the
      urinary excretion rate of torasemide during 0-30 min reached an upper plateau
      with respect to urine flow rate as well urinary excretion rates of sodium and
      chloride. Therefore, the diuretic effects (8-h urine output and 8-h urinary
      excretions of sodium and chloride) were not significantly different between the
      two groups of rats.

PMID- 12516077
TI  - Plasma concentration profiles of ketamine and norketamine after administration of
      various ketamine preparations to healthy Japanese volunteers.
AB  - Ketamine is known to provide analgesic effects without an anesthetic when
      administered in a low dose. We previously reported that a tablet containing
      ketamine had analgesic effects in patients with neuropathic pain. In the present
      study, we compared the plasma concentration profiles of the enantiomers of
      ketamine and its active metabolite, norketamine, up to 8 h after the
      administration of 20 mg of ketamine by injection, after the administration of two
      tablets containing 25 mg of ketamine, after the administration of two sublingual
      tablets containing 25 mg of ketamine, after the insertion of a suppository
      containing 50 mg of ketamine, and after the application of a nasal spray
      containing 25 mg of ketamine to three healthy volunteers. The plasma
      concentration of ketamine biexponentially declined after the administration by
      injection; the value of T(1/2beta) for ketamine was approximately 120 min. The
      bioavailability of the tablet was estimated to be approximately 20%; the area
      under the plasma concentration-time curve, (AUC)(0-->8 h), of norketamine was
      approximately 500 ng h/ml in both enantiomers. The bioavailabilities of the
      sublingual tablet and the suppository were estimated to both be approximately
      30%; the AUC(0-->8 h) of norketamine was 280-460 ng h/ml in both enantiomers. The
      plasma concentration profiles of the sublingual tablet and the suppository were
      almost similar to that of the tablet. The bioavailability of the nasal spray was
      estimated to be approximately 45%, which was the highest value among the
      preparations tested, and the AUC(0-->6 h) of norketamine was low (approximately
      100 ng h/ml) in both enantiomers. These pharmacokinetic findings suggested that
      all of the ketamine preparations tested in this study may be useful for the
      alleviation of neuropathic pain. We propose that the type of ketamine preparation
      should be selected in accordance with the patient's disease condition and the
      required dosage amount of ketamine.

PMID- 12516078
TI  - Characteristics of the gastric pH profiles of unfed and fed cynomolgus monkeys as
      pharmaceutical product development subjects.
AB  - Gastric pH is an important factor which significantly affects the dissolution of
      drugs, and therefore their bioavailability. In this study, the gastric pHs were
      measured directly with a miniature pH electrode inserted through the nostril into
      the body of the stomach of cynomolgus monkeys. Results from three separate sets
      of measurements using the same male monkeys indicated that the median gastric pH
      profiles of unfed monkeys were low, fluctuating between pH 1 and pH 3. However,
      the median gastric pHs in fed monkeys given about 108 g of a biscuit-type solid
      food, which are commonly provided, shifted toward a more neutral range between pH
      5 and pH 7, and remained in this range for about 9 h. This result contrasted with
      reported results for humans after eating a standard meal, which showed a neutral
      range between pH 5 and pH 7 for a brief period. Consequently, these results
      indicate that although the gastric pH of unfed cynomolgus monkeys is similar to
      that of fasting humans, there is a great difference in the gastric pH profiles
      between humans and monkeys after eating, which suggests that further studies are
      needed to establish optimal feeding conditions for bioavailability studies in
      monkeys.

PMID- 12516079
TI  - Effects of multipurpose solutions (MPS) for hydrogel contact lenses on gap
      junctional intercellular communication (GJIC) in rabbit corneal keratocytes.
AB  - To ensure the effects of multipurpose solutions (MPS) for hydrogel contact lenses
      on the cornea, the inhibitory activity of three types of MPS on corneal cells has
      been evaluated with the use of scrape loading and dye transfer assay (SLDT assay)
      and Western blotting on rabbit corneal keratocytes (RC4). In SLDT assay, MPS-A
      and poloxamine showed dose-dependent inhibitory activity, suggesting the
      inhibitory action of MPS-A and poloxamine to gap junctional intercellular
      communication (GJIC) in the tested cells. Moreover, after treatment with MPS-A,
      the GJIC was initially inhibited within 4 h, and thereafter gradually turned to
      an approximately 60% level of the initial value. When MPS-A was removed from the
      incubation media after exposure of the cells, the recovery of GJIC was time
      dependent and returned to approximately initial levels at 8 h. Complete recovery
      was established after approximately 24 h. These findings suggested that the
      inhibitory action of MPS-A on corneal keratocytes was reversible. This inhibition
      was accompanied by a decrease in the quantity of connexin-43, which is a major
      protein constituting the gap junctional channel of these cells, and its change in
      the phosphorylation state. Taken together, it was suggested that MPS-A interacts
      with connexin-43, inducing an inhibitory action on GJIC.

PMID- 12516080
TI  - Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds
      for bone ingrowth.
AB  - A novel approach to the manufacture of biodegradable polymeric scaffolds for
      tissue-engineering utilizing stereolithography (SLA) is presented. SLA is a three
      dimensional (3D) printing method that uses an ultraviolet laser to photo
      crosslink a liquid polymer substrate. The current generation of SLA devices
      provide a 3D printing resolution of 0.1 mm. The experiments utilized a
      biodegradable resin mixture of diethyl fumarate (DEF), poly(propylene fumarate)
      (PPF), and a photoinitiator, bisacylphosphine oxide (BAPO). The PPF is
      crosslinked with the use of the SLA's UV laser (325-nm wavelength). An SLA device
      was retrofitted with a custom fixture build tank enclosing an elevator-driven
      build table. A 3D prototype model testing the manufacturing control this device
      provides was created in a computer-aided-design package. The resulting geometric
      data were used to drive the SLA process, and a DEF/PPF prototype part was
      successfully manufactured. These scaffolds have application in the tissue
      engineering of bony substrates.

PMID- 12516081
TI  - Effect of processing variables on texture development in a mica-based glass
      ceramic.
AB  - The purpose of this study was primarily to determine the feasibility of heat
      pressing a mica-based glass-ceramic with the use of commercially available dental
      equipment, and secondly to evaluate the effect of various processing variables on
      the degree of crystal alignment in the pressed glass-ceramic. The hypotheses were
      that the mica-based glass-ceramic could be successfully heat-pressed and that
      some degree of crystal orientation would be obtained, depending on the processing
      variables. The glass composition was melted at 1400 degrees C for 2 h and cast
      into 12 x 60-mm rods. Ingots (10 x 12 mm) were cut from the glass rods, heat
      treated, and heat-pressed under various conditions. The microstructure of the
      pressed specimens was investigated by SEM and compared to that of heat-treated
      controls. The length of Vickers-induced cracks was measured on heat-pressed
      specimens and heat-treated controls. The results showed that mica-based glass
      ceramics could be successfully pressed with the use of commercially available
      dental equipment. The resulting degree of crystal alignment (texture) along the
      direction of pressing varied between 35 +/- 6 and 79 +/- 6. There was a linear
      relationship between the degree of texture and the apparent aspect ratio of the
      mica platelets. A significant decrease in the length of the Vickers-induced
      cracks in the direction perpendicular to pressing was observed, associated with
      an increase in length in the direction of pressing.

PMID- 12516082
TI  - In vitro corrosion testing of modular hip tapers.
AB  - The in vivo fretting behavior of modular hip prostheses was simulated to
      determine the effects of material combination and a unique TiN/AlN coating on
      fretting and corrosion at the taper interface. Fretting current, open-circuit
      potential (OCP), and quantities of soluble debris were measured to determine the
      role of mechanically assisted crevice corrosion on fretting and corrosion of
      modular hip tapers. Test groups consisting of similar-alloy (Co-Cr-Mo head/Co-Cr
      Mo neck), mixed-alloy (Co-Cr-Mo head/Ti-6Al-4V neck), and TiN/AlN-coated mixed
      alloy modular hip taper couples were used. Loads required to initiate fretting
      were similar for all test groups and were well below loads produced by walking
      and other physical activities. Decreases in OCP and increases in fretting current
      observed during long-term cyclic loading were indicative of fretting and
      corrosion. Current measured after cessation of cyclic loading suggests that once
      the conditions for crevice corrosion are established, corrosion can continue in
      the absence of loading. The chemical, mechanical, and electrochemical
      measurements, along with microscopic inspections of the taper surfaces indicate
      that the fretting and corrosion behavior of similar- and mixed-alloy taper
      couples are similar and that the coated samples are more resistant to fretting
      and corrosion. The results of this study clearly indicate the role of mechanical
      loading in the corrosion process, and support the hypothesis of mechanically
      assisted crevice corrosion.

PMID- 12516083
TI  - Antibiotic bone cement for the treatment of Pseudomonas aeruginosa in joint
      arthroplasty: comparison of tobramycin and gentamicin-loaded cements.
AB  - One hundred clinical isolates of Pseudomonas aeruginosa were collected from 22
      medical centers throughout Europe and were challenged with two aminoglycoside
      loaded bone cements, employing a modified in vitro Kirby-Bauer susceptibility
      model. The results of this study show that Simplex P with tobramycin exhibits
      antibacterial activity against 98% of the strains tested, compared to 93% for
      Palacos with gentamicin. Additionally, for strains that were susceptible to the
      antibiotic bone cement formulations, the average zone of inhibition produced
      around the tobramycin-loaded cement disks was approximately 25% greater than that
      seen around the gentamicin-loaded cement disks. This difference was statistically
      significant (p << 0.01). Tobramycin-loaded bone cement is therefore the preferred
      formulation when addressing Pseudomonas aeruginosa in septic joint arthroplasty.

PMID- 12516084
TI  - Surface composition analysis of failed cementless CoCr- and Ti-base-alloy total
      hip implants.
AB  - The surfaces of retrieved failed cementless total hip implants made of cobalt
      chromium-molybdenum casting alloy and of wrought titanium 6-aluminum 4-vanadium
      alloy were studied with the use of scanning-electron microscopy (SEM), energy
      dispersive X-ray analysis (EDX) and X-ray photoelectron spectroscopy (XPS). New
      implants of the same make served as controls. The XPS scans revealed a dense
      carbon layer on the entire analyzed specimen. The relative composition of the
      titanium alloy implants showed an overall agreement with the international
      standards for implants for surgery, and the overall surface composition did not
      change over the period of the implantation. However, an inhomogeneous
      distribution of the constituents could be demonstrated in the retrieved as well
      as in the new MEC-screw rings made of TiAl6V4 alloy, an implant that has been
      linked to a high early failure rate. In the CoCr-alloy components (Lord-screw
      rings) a high percentage of aluminum, mainly organized in aluminum inclusions,
      was found in the retrieved as well as in the new implants.

PMID- 12516085
TI  - Porous titanium-nickel for intervertebral fusion in a sheep model: part 1.
      Histomorphometric and radiological analysis.
AB  - Porous titanium-nickel (PTN) implants represent an alternative to traditional
      intervertebral fusion cages. Indeed, PTN materials possess interconnecting pores
      with cell capillarity properties that may promote bone ingrowth and
      intervertebral fusion without the need for bone grafting. In this study, a PTN
      intervertebral fusion device was compared to a conventional TiAlV cage packed
      with autologous bone in a sheep model. The two devices were implanted at two
      noncontiguous intervertebral lumbar sites for 3, 6, and 12 months. PTN
      osseointegration showed a time-dependent trend increasing from 21.4% to 37.6% (3
      12 months), whereas TiAlV cages remained at the same level of bone ingrowth
      (22.7%-25.4%; 3-12 months). Furthermore, PTN bone apposition (10.9%-24.2%; 3-12
      months) was significantly higher than that of TiAlV implants (1.1%-5.1%; 3-12
      months; p < 0.001, ANOVA). Radiological fusion scores increased with postsurgery
      time regardless of material type, but were consistently superior for PTN (12.5
      18.5; 3-12 months) than for TiAlV cages (2.0-15.0; 3-12 months; p < 0.001,
      ANOVA). Implant materials were not significantly different according to the
      radiological interbody index based on preoperative disc height: Interbody index
      began at 132.6% (PTN) and 123.5% (TiAlV) immediately after surgery, then declined
      to 80.8% (PTN) and 91.0% (TiAlV) after 12 months. Nevertheless, ungrafted PTN
      constituted an excellent substrate for osteogenic cell integration and represents
      a new osteoconductive biomaterial with improved fusion characteristics in
      comparison to conventional TiAlV cages.

PMID- 12516086
TI  - Porous titanium-nickel for intervertebral fusion in a sheep model: part 2.
      Surface analysis and nickel release assessment.
AB  - Porous titanium-nickel (PTN) devices represent an alternative to traditional cage
      implants. PTN materials possess an interconnecting network of pores with
      capillarity properties that may promote bone ingrowth, long-term fixation, and
      intervertebral fusion without the need for bone grafting. However, their
      considerable surface area and nickel content may elicit concerns over
      sensitization potential. Therefore, PTN surface corrosion and nickel release
      resistance must be carefully studied. To evaluate this possibility, a PTN
      interbody fusion device (IFD) was compared to a conventional nonporous cage made
      of TiAlV, a well-known biocompatible biomaterial, in a sheep model. PTN and TiAlV
      IFDs were inserted at two non-contiguous lumbar sites for 3, 6, and 12 months
      postsurgery. Their surface was then evaluated by scanning electron microscopy
      (SEM) combined with backscattered electron analysis (BSE). No evidence of surface
      corrosion was observed either pre- or postimplantation, regardless of device
      type. Dosage of nickel ions was also performed with the use of inductively
      coupled plasma-mass spectrometry (ICP-MS). Blood nickel levels were observed to
      be within acceptable levels at all postinstrumentation times. Nickel content in
      PTN-adjacent tissue, as well as in detoxification and remote organs, was
      equivalent both in PTN-treated and control sheep. Therefore, porous titanium
      nickel demonstrated resistance to both in vivo surface corrosion and nickel ion
      release and compared very well with a conventional titanium implant in the course
      of a 12-month sheep study.

PMID- 12516087
TI  - Relationship between steroid hormone contraceptives and HPV, cervical
      intraepithelial neoplasia and cervical carcinoma.
AB  - Available data demonstrate an increase in the transcription of high-risk
      papillomaviruses by the 16alpha-hydroxylation of estrogens, which is in line with
      the epidemiologic data showing an increased cervical carcinogenesis risk for long
      term contraceptive-using, HPV-infected women. No evidence exists for an increase
      in HPV-negative contraceptive users.

PMID- 12516088
TI  - Matrix metalloproteinase-19 is expressed by proliferating epithelium but
      disappears with neoplastic dedifferentiation.
AB  - MMP-19 (also designated RASI) is a recently discovered member of a large family
      of zinc-dependent proteolytic enzymes, most of which have been implicated in
      cancer growth and metastasis. It differs from the others by its chromosomal
      location and structure and is expressed by endothelial and vascular smooth muscle
      cells in vivo. Our aim was to study the putative role of MMP-19 in skin cancer.
      We also examined its regulation in keratinocyte cultures using quantitative
      TaqMan RT-PCR. Our results show that MMP-19 can also be detected in stimulated
      keratinocytes by Northern and Western analyses. In wounds, it was found in
      keratinocytes outside the migrating area, while in BCC and SCC, it was present in
      the hyperproliferative (p63-positive), E-cadherin-negative epidermis at the tumor
      surface but downregulated in invasive cancer islands. Expression was also evident
      in endothelial cells of neoangiogenic regions and in occasional stromal
      fibroblasts. Of the 12 tested cytokines/growth factors, only TNF-alpha and PMA
      were able to stimulate the expression of MMP-19 mRNA in primary keratinocytes. No
      MMP-19 mRNA was detected by Northern analysis in cultured HaCaT or A5 cells or in
      an SCC cell line established from head-and-neck cancer. Our data suggest that,
      unlike most MMPs, MMP-19 expression in the epidermis is downregulated during
      transformation and histologic dedifferentiation.

PMID- 12516089
TI  - Tyrosine-nitration of caspase 3 and cytochrome c does not suppress apoptosis
      induction in squamous cell carcinoma cells.
AB  - The influence of tyrosine nitration of cytochrome c and caspase 3 on apoptosis
      induction was investigated in an established squamous carcinoma cell line, OSC-4.
      The intracellular NO and O2(-) levels were increased up to about 110-120% and 140
      180% of the control levels, respectively, after the treatment of OSC-4 cells with
      5-FU (100 microg/ml), PLM (10 microg/ml), CDDP (10 microg/ml), or gamma-rays (20
      Gy). The treatment of OSC-4 cells with ONOO(-) (1 mM) and the above anticancer
      agents induced tyrosine nitration of 14, 32 kDa protein among others and
      nitration of tyrosine residues of cytochrome c and caspase 3 was identified by
      the Western blotting of immunoprecipitates obtained by antibodies to these
      proapoptotic proteins. When cytochrome c and procaspase 3 were treated with ONOO(
      ), tyrosine nitration was increased in a ONOO(-)-dose dependent manner. Tyrosine
      nitration of cleaved (17 kDa) caspase 3, however, was not induced by ONOO(-).
      Procaspase 3 in the cytosol of HeLa cells was activated by the addition of ONOO(
      )-treated as well as ONOO(-)-untreated cytochrome c. In addition, cleavage of
      ICAD and PARP were not suppressed in OSC-4 cells by pretreatment with ONOO(-).
      Activity of cleaved caspase 3 was not suppressed at low concentrations or by
      treatment with ONOO(-) or NO donors, SIN-1 and SNP. Furthermore, apoptosis of OSC
      4 cells by the anticancer agents was not suppressed by ONOO(-). In conclusion,
      these results suggest that nitration of tyrosine residues of cytochrome c and
      procaspase 3 is induced by chemoradiotherapy but their nitration does not
      suppress cancer cell apoptosis.

PMID- 12516090
TI  - Expression of the coxsackie and adenovirus receptor in human astrocytic tumors
      and xenografts.
AB  - The sensitivity of human tissues and tumors to infection with type C adenoviruses
      correlates with the expression of the human coxsackie B- and adenovirus receptor,
      hCAR. HCAR is heterogeneously expressed in various tissues and types of human
      cancer cells, which has implications for the use of adenoviruses as vectors in
      cancer gene therapy. Using immunoblotting, real-time PCR, FACS-analysis and
      sensitivity to infection with adenovirus-lacZ, we analyzed the expression level
      of hCAR in glioma Grade IV cell lines. With real-time PCR, we also analyzed hCAR
      expression in primary human astrocytomas of different malignancy grades, as well
      as in their xenograft derivatives. Analysis of a set of 10 cell lines showed
      great variation in hCAR expression. Susceptibility to Ad5lacZ correlated well
      with hCAR expression, whereas no correlation was observed with the expression of
      alphavbeta3/alphavbeta5 integrins, proposed to function as co-receptors for
      adenoviruses. A great variation of CAR expression was also observed in primary
      astrocytomas of different malignancy grades. The mean value of CAR expression was
      significantly lower in 22 Grade IV tumors as compared to the values for 6 Grade
      II (p = 0.01) and 6 Grade III (p = 0.01) tumors. When the hCAR expression in 11
      xenografts derived from Grade IV gliomas were compared to the levels detected in
      the original parental tumors, a mean 12-fold higher expression was seen in the
      xenografts (P = 0.01). Two xenografts with low hCAR expression grew considerably
      faster than the hCAR-expressing cells. Our results have relevance for the use of
      adenoviruses in gene therapy against astrocytomas.

PMID- 12516091
TI  - Allelic imbalance at 11p15.5-15.4 correlated with c-Ha-ras mutation during
      radiation-induced neoplastic transformation of human breast epithelial cells.
AB  - Breast cancer is the most frequent malignancy in women throughout much of the
      developed world and is associated with a multistage process involving a number of
      genetic mutations and their corresponding cellular phenotypic alterations. It has
      already been shown that neoplastic transformation of a spontaneously immortalized
      human breast epithelial (MCF-10F) cell line by radiation, in combination with
      estrogen, represents a successful model in studying the molecular and biological
      alterations that may contribute to the tumorigenic process. In the present study,
      the incidence of allelic alterations (microsatellite instability/loss of
      heterozygosity) on chromosome 11 in different radiation-induced primary and
      secondary tumorigenic cell lines, relative to the control MCF-10F cells was
      investigated. We identified 3 regions of the chromosome 11 (11p15-p15.5, 11q13
      and 11q23) that showed high incidence of LOH among these tumor cell lines and
      suggested a potential role for these chromosomal regions in breast
      carcinogenesis. Among them, locus 11p15.5, where c-Ha-ras oncogene is located,
      had incidence of allelic imbalance between 25-40%. Furthermore, direct sequencing
      analysis of codons 12 and 61 of the c-Ha-ras oncogene identified various point
      mutations. These data highlight the importance of chromosome 11 in radiation
      induced malignant transformation of human breast epithelial cells and suggest the
      usefulness of the model in uncovering specific derangements during breast cancer
      progression.

PMID- 12516092
TI  - Suppression of insulin-induced AP-1 transactivation by menin accompanies
      inhibition of c-Fos induction.
AB  - The translation product of the MEN1 gene, menin, has been reported to suppress
      JunD-mediated activator protein-1 (AP-1) transactivation and inhibit Ras-mediated
      tumor formation, but its molecular mechanisms and physiologic significance have
      been poorly elucidated. To better understand the function of menin as a tumor
      suppressor, we examined the effect of menin on physiologically induced AP-1
      activity. Overexpression of menin strongly suppressed insulin-induced AP-1
      activity in CHO-IR cells, which express high levels of insulin receptor. We found
      that menin suppressed c-Fos induction at the transcriptional level, although that
      cannot explain the entire mechanism of AP-1 suppression by menin. Menin did not
      alter the expression levels of AP-1 proteins except c-Fos, phosphorylation of c
      Jun and JunD and DNA binding properties of AP-1 proteins. Suppression of AP-1
      activation by menin may be exerted through 2 independent mechanisms, direct
      inhibition on AP-1-mediated transcription and suppression of c-Fos induction. The
      molecular mechanism of inhibition of AP-1 function by menin needs further
      elucidation.

PMID- 12516093
TI  - Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in
      Taiwanese.
AB  - NPC is an epithelial tumor that is highly prevalent among the southern Chinese.
      Numerous studies have indicated that specific HLA haplotypes and genes within the
      HLA complex are associated with NPC. As a first effort to localize the gene
      responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for
      their association to NPC. Consistent with previous reports, frequencies of HLA-A2
      [OR = 2.50, pc = 0.020 (study population); OR = 3.73, pc = 0.0030 (> or =40 years
      old)] were significantly higher in patients with NPC than in healthy controls.
      Two-locus analysis indicated that A2(+)B46(+) individuals are at greater risk for
      NPC than A2(-)B46(-) individuals in both the population studied and the > or =40
      year-old group. This, however, may be due to the close linkage of these 2 genes.
      Moreover, A2(+)B38(+) individuals were at higher risk than A2(-)B38(-)
      individuals in both the population studied and the > or =40-year-old group; A2
      and B38 are not genetically linked. These findings suggest that B38 or B46 alone
      cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46
      positivity greatly increases risk. None of 5 A2 subtypes identified from studied
      populations was significantly associated with NPC. Microsatellite marker D6S211,
      located 97 kb telomeric to HLA-A, was analyzed for its association with NPC.
      Allele 4 of D6S211 was significantly associated with NPC (OR = 3.97, pc =
      0.0042). These results strongly support the hypothesis that genes associated with
      susceptibility to NPC in the HLA region are within the HLA-A locus.

PMID- 12516094
TI  - Association of genomic imbalances with drug resistance and thermoresistance in
      human gastric carcinoma cells.
AB  - Therapy resistance is the major obstacle to advances in successful cancer
      treatment. To characterize chromosomal alterations associated with different
      types of acquired MDR and thermoresistance, we applied CGH to compare a unique
      panel of human gastric carcinoma cells consisting of the parental, drug-sensitive
      and thermosensitive cancer cell line EPG85-257P, the atypical MDR variant EPG85
      257RNOV, the classical MDR subline EPG85-257RDB and their thermoresistant
      counterparts EPG85-257P-TR, EPG85-257RNOV-TR and EPG85-257RDB-TR. CGH with
      genomic DNA prepared from these cell lines as probes successfully identified
      genomic gains and/or losses in chromosomal regions encoding putative genes
      associated with drug resistance and/or thermoresistance. These genes included
      various members of the families of ABC transporters and molecular chaperones. The
      importance of these cell variant-specific genomic imbalances in the development
      of MDR and thermoresistance is discussed and remains to be elucidated.

PMID- 12516095
TI  - Complete loss of HLA class I antigen expression on melanoma cells: a result of
      successive mutational events.
AB  - Alterations in the surface expression of HLA class I molecules have been
      described as a strategy of tumors to evade recognition by cytotoxic T cells. We
      detected complete loss of HLA class I antigen presentation for 2 tumor cell lines
      from 1 melanoma patient, the first originated from a regional lymph node lesion
      diagnosed simultaneously with the primary tumor and the second established 8
      months later from a metastatic pleural effusion sample. Antigen presentation was
      not inducible with IFN-gamma but could be restored after transfection of tumor
      cells with b2m cDNA, indicating a defect in b2m expression. Analysis of the
      nature of this defect revealed that it originated from at least 2 mutational
      events affecting both copies of the b2m gene: a microdeletion of 498 bp in one
      b2m gene, including its entire exon 1, and a macrodeletion involving the entire
      copy of the second b2m gene. Microsatellite analysis pointed to the macrodeletion
      by demonstrating LOH for several specific markers on the long arm (q) of
      chromosome 15. Structural imbalance of 15q was verified by FISH. FISH studies
      also indicated the coexistence of a structurally abnormal variant of chromosome
      15q with 2 apparently entire chromosomes 15q harboring the homozygous b2m
      microdeletion. Block of b2m expression in tumor cells builds a barrier to
      immunotherapy of cancer patients, and its early incidence should be of major
      consideration in the development and design of immunotherapeutic strategies.

PMID- 12516096
TI  - Characterization of the human Ly-6 antigens, the newly annotated member Ly-6K
      included, as molecular markers for head-and-neck squamous cell carcinoma.
AB  - The E48 antigen is a successfully explored molecular marker for the diagnosis and
      therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen,
      however, is restricted due to its heterogeneous expression in 30% of tumors; and
      identification of additional target antigens is therefore desired. E48 belongs to
      the Ly-6 antigen family, comprising a group of highly homologous, low m.w., GPI
      anchored surface proteins, of which some show tissue-restricted expression
      patterns. To identify novel human HNSCC-associated Ly-6 members with squamous
      cell-associated expression patterns, we performed comprehensive gene-screening
      consisting of BLAST searches within GenBank databases, followed by expression
      analysis. Using this approach, the Ly-6K gene could be annotated as a novel
      member of the human Ly-6 family. Expression of the human Ly-6 genes E48, Ly-6K,
      PSCA, GML, RIG-E, G6C and Ly-6H was prescreened by qualitative RT-PCR and
      subsequently analyzed by quantitative RT-PCR in normal keratinocytes, HNSCC cell
      lines, normal mucosa, HNSCC tumors as well as normal peripheral blood and bone
      marrow cells. PSCA was highly expressed in normal mucosa, but 100-fold decreased
      expression was seen in HNSCC. For Ly-6H, GML and G6C, no or very low expression
      was observed in keratinocytes and HNSCC. Expression of RIG-E was high in normal
      and malignant squamous cells and in peripheral blood and bone marrow cells, thus
      limiting its applicability as an HNSCC-associated marker. In contrast, besides
      the E48 gene, the Ly-6K gene also appeared to be selectively expressed in HNSCC
      and normal squamous cells. Moreover, expression of Ly-6K was shown in HNSCC cell
      lines, in which no E48 expression could be detected. These data justify further
      evaluation of Ly-6K as potential target antigen for the diagnosis and therapy of
      HNSCC.

PMID- 12516097
TI  - Continuous long-term monitoring of UV radiation in professional mountain guides
      reveals extremely high exposure.
AB  - Ultraviolet radiation (UVR) is estimated to be one of the most important risk
      factors for nonmelanoma and melanoma skin cancers. High occupational UV exposure
      is assumed to be associated with skin cancer. Mountain guides receive
      considerable UV doses due to altitude-related increase of UVR and reflection from
      snow- and ice-covered surfaces. The aim of our study was to assess the annual
      occupational UV exposure of mountain guides. Spore film test chambers containing
      spores of Bacillus subtilis (VioSpor) were used as UV dosimeters with a spectral
      sensitivity profile similar to erythema-weighted data calculated from
      spectroradiometric measurements. Nine mountain guide instructors carried
      dosimeters on the sides of their heads on a total of 1,406 working days during
      one year (July 1999-June 2000). Dosimeters were changed monthly. Measurements of
      92 months could be evaluated (4-12 months/mountain guide). The mean individual
      monthly UV exposure was 107 standard erythema doses (SED) (median 71 SED; range
      10-505 SED). The mean annual cumulative UV exposure was 1,097 SED (median 1,273
      SED; range 312-1,770 SED) per mountain guide. The mean UV dose per day (4-10 hr)
      was 6.6 SED (median 5.7 SED; range 0.6-24.2 SED). This is the second study of
      continuous annual UV dosimetry in a cohort of outdoor workers. Our study showed
      that it is not sufficient to interpolate annual UV exposure from a few days'
      measurements. Only long-term dosimetry can give reliable yearly information of
      UVR load. Median daily UV exposure exceeded limits for UV radiation (e.g., ACGIH
      effective dose 30 J/m(2) per 8 hr period corresponding to 1.08 SED/day) 6-fold;
      maximal exposure exceeded these limits 23-fold. These extremely high exposure
      values are suggestive for an increased risk of skin cancer and thorough
      epidemiologic studies in the collectives of professional and recreational
      mountaineering are required.

PMID- 12516098
TI  - The patched polymorphism Pro1315Leu (C3944T) may modulate the association between
      use of oral contraceptives and breast cancer risk.
AB  - The gene coding for the human homologue of the Drosophila segment polarity gene
      patched (PTCH1) is mutated in several common human tumors. In mice,
      haplodeficiency at the Ptch1 locus results in severe histologic defects in
      mammary ductal structure. We found no mutations within the coding region of PTCH1
      in 17 human primary breast carcinomas. However, the biallelic Pro1315Leu (C3944T)
      polymorphism of PTCH1 was significantly associated with breast cancer in 41
      Bavarian patients compared to 85 healthy controls. We investigated whether this
      variant influences susceptibility for breast cancer in 611 breast cancer patients
      diagnosed by age 50 years and 1,057 controls matched by age and study region in
      Germany and in 1,093 breast cancer patients from the United Kingdom. Allele and
      genotype frequencies were not different between cases and controls. However,
      multivariate logistic regression analysis revealed an effect modification of oral
      contraceptive use (OC) on breast cancer risk by Leu-carrier status. Compared to
      women who have Pro/Pro and never used OC, Pro/Pro OC users had an increased odds
      ratio for breast cancer of 1.7. The odds ratio was also 1.7 for Leu-carriers who
      never used OC, but this was attenuated among Leu-carriers who ever used OC by
      20%. The gene-environmental interaction was confirmed in case-only analysis of
      the German and British studies, yielding an interaction odds ratio of 0.7 for
      premenopausal women (p = 0.06). Longer duration of pill use was associated with a
      significantly greater risk reduction (p for trend = 0.015). Our novel observation
      of a differential effect of OC use on breast cancer risk by PTCH1 1315Leu-carrier
      status suggests the interesting possibility of the Sonic hedgehog/Patched
      (SHH/PTCH1) signaling pathway being involved in hormone-induced development of
      breast carcinoma.

PMID- 12516099
TI  - Does skin fibroblast radiosensitivity predict squamous cancer cell
      radiosensitivity of the same individual?
AB  - Individualization of radiation doses is presumed to result in better radiotherapy
      outcome. Success rate in measuring radiosensitivity is probably the most limiting
      factor for present radiosensitivity assays to be introduced into clinical
      routine. To find a simpler predictive parameter, we compared the radiosensitivity
      of dermal fibroblasts and head and neck squamous cell carcinoma (SCC) cell lines
      established from the same individuals. The radiosensitivity was tested using the
      clonogenic 96-well plate assay. The surviving fraction at 2.0 Gy (SF2) was
      determined, as well as the mean inactivation dose (AUC) of cancer cells. SF2 of
      SCC cell lines and skin fibroblasts were 0.25-0.44 and 0.11-0.43, respectively.
      AUC of SCC cells was 1.4-2.1 Gy. Dermal fibroblasts were more radiosensitive than
      SCC cells in 14 of 15 cases. In 1 patient (UT-SCC-8), cancer cells were found to
      be more radiosensitive than corresponding dermal fibroblasts. There was a clear
      tendency to a correlation between radiosensitivities of these 2 cell types, but
      statistical significance was reached only when the data of UT-SCC-8 was excluded.
      In our material, the intrinsic radiosensitivity of head and neck SCC cells could
      in most cases be predicted from the intrinsic radiosensitivity of dermal
      fibroblasts established from the same individual.

PMID- 12516100
TI  - Early life risk factors in cancer: the relation of birth weight to adult obesity.
AB  - The intrauterine environment appears to play a role in the development of adult
      diseases, including several prominent cancers. Our study aims to characterize the
      relationship between birth weight, a measure of the intrauterine environment, and
      adult obesity. A population-based sample of women aged 50-79, living in the
      states of Massachusetts, New Hampshire or Wisconsin, were randomly selected from
      lists of licensed drivers and Medicare beneficiaries to participate as controls
      in a case-control study of breast cancer. Information on birth weight, adult
      height and adult weight were collected through structured telephone interviews
      from 1992-1995. Our analysis was based on 1,850 interviews. A U-shaped
      relationship between birth weight and adult BMI was observed. Median adult BMI
      for the birth weight categories (in kilograms) <2.3, 2.3<2.5, 2.5<3.2, 3.2<3.9,
      3.9<4.5 and > or =4.5 were 26.6, 24.4, 25.1, 25.5, 25.4 and 26.6 kg/m
      respectively. Compared to women 2.5<3.2 kg at birth, women in highest birth
      weight category (> or =4.5 kg) had an odds ratio of 1.99 (95% CI 1.13-3.48) of
      being obese (> or =30 kg/m(2)) as adults. The odds ratio for women in the <2.3 kg
      birth weight category was 1.67 (95% CI 1.01-2.76). These data suggest that both
      low and high birth weights are associated with higher adult BMI and support the
      hypothesis that fetal experience may influence adult obesity with potential
      consequences for risk of several major cancers.

PMID- 12516101
TI  - Impact of comorbidity on lung cancer survival.
AB  - Lung cancer is associated with smoking and age, both of which are associated with
      comorbidity. We evaluated the impact of comorbidity on lung cancer survival. Data
      on 56 comorbidities were abstracted from the records of a cohort of 1,155
      patients. Survival effects were evaluated with Cox regression (outcome crude
      death). The adjusted R(2) statistic was used to compare the survival variation
      explained by predictive variables. No comorbidity was observed in 11.7% of
      patients, while 54.3% had 3 or more (mean 2.97) comorbidities. In multivariate
      analysis, 19 comorbidities were associated with survival: HIV/AIDS, tuberculosis,
      previous metastatic cancer, thyroid/glandular diseases, electrolyte imbalance,
      anemia, other blood diseases, dementia, neurologic disease, congestive heart
      failure, COPD, asthma, pulmonary fibrosis, liver disease, gastrointestinal
      bleeding, renal disease, connective tissue disease, osteoporosis and peripheral
      vascular disease. Only the latter was protective. Some of the hazards of
      comorbidities were explained by more directly acting comorbidities and/or receipt
      of treatment. Stage explained 25.4% of the survival variation. In addition to
      stage, the 19 comorbidities explained 6.1%, treatments 9.2%, age 3.7% and
      histology 1.3%. Thirteen uncommon comorbidities (prevalence <6%) affected 21.2%
      of patients and explained 3.5% of the survival variation. Comorbidity count and
      the Charlson index were significant predictors but explained only 2.5% and 2.0%
      of the survival variation, respectively. Comorbidity has a major impact on
      survival in early- and late-stage disease, and even infrequent deleterious
      comorbidities are important collectively. Comorbidity count and the Charlson
      index failed to capture much information. Clinical practice and trials need to
      consider the effect of comorbidity in lung cancer patients.

PMID- 12516102
TI  - Prevalence of specific types of human papillomavirus and cervical squamous
      intraepithelial lesions in consecutive, previously unscreened, West-African women
      over 35 years of age.
AB  - Previous studies among women worldwide have demonstrated that infection with
      specific types of human papillomaviruses (HPV) is central to the pathogenesis of
      cervical neoplasia. There is little data, however, concerning the prevalence of
      specific HPV types and the association of each type with cervical neoplasia among
      women in sub-Saharan Africa, who remain at very high risk of cervical cancer. We
      studied 2,065 consecutive patients aged 35 years or older, presenting to
      community health clinics in Dakar and Pikine, West Africa, who had not been
      screened previously for cytologic abnormalities or HPV. Cytologic diagnosis and
      HPV detection were accomplished using a ThinPrep Pap and a polymerase chain
      reaction-based reverse-line strip assay, respectively. Odds ratios (OR) and
      associated 95% confidence intervals (CI) were estimated using polynomial logistic
      regression. Cytologic abnormalities were found in 426 women (20%), including 254
      (12%) with atypical squamous cells of undetermined significance, 86 (4%) with low
      grade squamous intraepithelial lesions, 66 (3%) with high-grade squamous
      intraepithelial lesions (HSIL) and 20 (1%) with invasive cancer. HPV infection
      was detected in 18%. Among women with negative cytologic findings, the prevalence
      of high risk but not low risk HPV types increased with age. HPV16 (2.4%) and
      HPV58 (1.6%) were the most frequently detected HPV types in this population, as
      well as being the most strongly associated with risk of HSIL/cancer (HPV16: OR =
      88, 95% CI = 39-200; HPV58: OR = 51, 95% CI = 16-161). These data suggest that in
      addition to HPV16, HPV58 should be considered in the strategic planning of
      vaccination against cervical cancer in this geographic region.

PMID- 12516103
TI  - Association between a glutathione S-transferase A1 promoter polymorphism and
      survival after breast cancer treatment.
AB  - Glutathione S-transferase (GST) enzymes detoxify chemotherapeutic drugs, and
      several studies have reported differences in survival for cancer patients who
      have variant genotypes for GSTP1, GSTM1 or GSTT1 enzymes. A recently described
      polymorphism alters hepatic expression of GSTA1, a GST with high activity in
      glutathione conjugation of metabolites of cyclophosphamide (CP). To consider the
      possible influence of the reduced-expression GSTA1*B allele on cancer patient
      survival, we have conducted a pilot study of breast cancer patients treated with
      CP-containing combination chemotherapy. GSTA1 genotype was determined by
      polymerase chain reaction and restriction fragment length polymorphism. Kaplan
      Meier methods and Cox proportional hazards models were used to evaluate survival
      in relation to genotype. Among 245 subjects, 35% were GSTA1*A/*A, 49% GSTA1*A/*B
      and 16% GSTA1*B/*B; the genotype distribution did not differ by ethnic group, age
      or stage at diagnosis. Among patients who had 0 or 1 GSTA1*B allele, the
      proportion surviving at 5 years was 0.66 (95% CI = 0.59-0.72), whereas for
      GSTA1*B/*B subjects the proportion was higher, 0.86 (95% CI = 0.67-0.95).
      Significantly reduced hazard of death was observed for GSTA1*B/*B subjects during
      the first 5 years after diagnosis, hazard ratio (HR) = 0.3, 95% CI = 0.1-0.8. The
      association varied with time, with no survival difference observed for subjects
      who survived beyond 5 years. These results, although based on a small study
      population, describe an apparent difference in survival after treatment for
      breast cancer according to GSTA1 genotype. Further studies should consider the
      possible association between the novel GSTA1*B variant and outcomes of cancer
      therapy.

PMID- 12516104
TI  - Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the
      stomach and esophagus.
AB  - Infection with Helicobacter pylori (H. pylori), especially CagA+ strains, has
      been associated with an increased risk of noncardia gastric adenocarcinoma. The
      relationship with junctional cancer (adenocarcinomas of the esophagus and gastric
      cardia combined) has not been adequately investigated, although some studies have
      reported a reduced risk associated with H. pylori and CagA seroseropositivity. We
      investigated this question in a subset of cases and controls from a recently
      completed, large population-based case-control study of gastric and esophageal
      adenocarcinomas in Los Angeles County. Using established antigen-specific ELISAs,
      serum IgG antibodies to H. pylori whole-cell antigens (Helico-G) and CagA were
      measured in population controls (n = 356) and patients with incident esophageal
      adenocarcinoma (n = 80), gastric cardia cancer (n = 87) or distal gastric cancers
      (noncardia gastric adenocarcinoma) (n = 127). After controlling for demographic
      characteristics (age, gender, race, birthplace, education), smoking and body mass
      index, seropositivity for H. pylori was associated with a statistically
      significant increased risk of distal gastric cancer (adjusted odds ratio [OR] =
      1.85, 95% confidence interval [CI] = 1.03, 3.32) but the risk of junctional
      cancer was not increased (adjusted OR = 1.26, 95% CI = 0.82, 1.94). The risk of
      junctional cancer was not changed when CagA and H. pylori were both considered,
      but the risk of distal gastric cancer was further increased. Subjects who were
      seropositive for both CagA and H. pylori compared to those who were seronegative
      for H. pylori showed a risk of 2.20 (95% CI = 1.13, 4.26) for distal gastric
      cancer and 0.86 (95% CI = 0.47, 1.59) for junctional cancer. Although tests for
      interaction between smoking and H. pylori were not statistically significant for
      junctional or distal gastric cancers, risk for both tumor types tended to be
      higher among current smokers who were also H. pylori seropositive. In conclusion,
      we find no evidence that infection with CagA+ strains of H. pylori reduces risk
      of esophageal and gastric cardia adenocarcinoma in this population. Our findings
      confirm the positive association between risk of distal gastric cancer and
      infection with H. pylori infection, especially CagA+ strains.

PMID- 12516105
TI  - A third-generation matrix metalloproteinase (MMP) inhibitor (ONO-4817) combined
      with docetaxel suppresses progression of lung micrometastasis of MMP-expressing
      tumor cells in nude mice.
AB  - The lung is the common target organ of hematogenous metastasis that restricts the
      prognosis of cancer patients. MMPs play a pivotal role in metastasis by promoting
      tumor invasion and angiogenesis; therefore, a large number of MMPIs have been
      developed. Our purpose was to determine the therapeutic efficacy of a selective
      spectrum MMPI, ONO-4817 (inhibits MMP-2 and MMP-9 but not MMP-1), against
      established lung micrometastasis in combination with a cytotoxic anticancer drug,
      DOC, in a nude mouse model. Human non-small cell lung cancer PC14PE6
      (adenocarcinoma) or H226 (squamous cell carcinoma) cells, expressing MMP-2, MMP-9
      and/or MMP-1, were injected i.v. into nude mice on day 0. Mice received a single
      injection of DOC on day 7 (after establishment of micrometastasis) and/or ONO
      4817 mixed with food from day 7 to the end of experiments. Monotherapy with ONO
      4817 or DOC inhibited formation of lung metastasis by PC14PE6 and H226 cells. In
      addition, combined use of ONO-4817 with DOC significantly suppressed the tumor
      burden of H226 and PC14PE6 cells in the lung and prolonged the survival of
      PC14PE6-bearing mice compared to ONO-4817 or DOC alone. These therapies did not
      affect the body weight or food intake of tumor-bearing mice. FIZ revealed that
      lung lesions, but not nontumor parenchyma of the lung, expressed gelatinolytic
      activity and that treatment with ONO-4817 abrogated the gelatinolytic activity in
      lung lesions. These results suggest that the combined use of MMPIs with cytotoxic
      anticancer drugs may be helpful in the control of established lung
      micrometastasis by tumor cells expressing MMPs.

PMID- 12516106
TI  - A randomised, double-blind, placebo-controlled trial of photodynamic therapy
      using 5-aminolaevulinic acid for the treatment of cervical intraepithelial
      neoplasia.
AB  - Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (ALA) has been
      used to treat histologically confirmed cervical intraepithelial neoplasia (CIN-I
      and -I/II) in a randomised, double-blind, placebo-controlled protocol.
      Fluorescence microscopy revealed that topical application of 3% ALA in Intrasite
      Gel to the cervix for 3 hr resulted in the accumulation of protoporphyrin IX in
      the cervical epithelium. Treatment of CIN with ALA-PDT was well tolerated, with
      only 3/12 patients in the PDT arm (0/13 in the placebo arm) reporting any
      discomfort during illumination. Histologic examination of the treated tissue
      following loop excision 3 months post-PDT indicated that 33% of patients had no
      evidence of CIN, 42% had no change in the grade of their disease, whilst 25%
      exhibited an apparent progression of disease. In the control group, the
      respective figures were 31%, 38% and 31%. There was no significant difference in
      response between the groups receiving ALA-PDT and those receiving placebo
      treatment.

PMID- 12516107
TI  - Ectopic p21sdi1 gene transfer induces retinoic acid receptor beta expression and
      sensitizes human cancer cells to retinoid treatment.
AB  - The biological effects of retinoic acid (RA) are mediated by nuclear retinoic
      acid receptors (RARs) that function as ligand-activated transcriptional factors.
      The response of human cancer cells to RA is known to be associated with the
      expression of RARbeta. Recent studies have demonstrated that the loss of RARbeta
      expression is involved in the development of a variety of human malignancies. We
      show that recombinant adenovirus-mediated p21(sdi1) gene transfer enhances
      RARbeta mRNA expression as well as protein expression and induces the sensitivity
      to all-trans RA (ATRA) in human cancer cells. Semi-quantitative reverse
      transcription-polymerase chain reaction analysis demonstrated that infection with
      adenovirus carrying human p21(sdi1) gene (Ad5CMV-p21), which encodes a cyclin
      dependent kinase inhibitor, induced RARbeta mRNA and protein expression in H1299
      human non-small cell lung cancer cells and DLD-1 human colorectal cancer cells.
      We also found that exogenous introduction of the p21(sdi1) gene transcriptionally
      activated the upstream promoter function of the RARbeta gene. Treatment with 1
      microM of ATRA showed no significant inhibitory effects on the growth of H1299
      and DLD-1 cells; after Ad5CMV-p21 infection, however, cells underwent apoptosis
      with ATRA treatment at the same concentration, suggesting that p21(sdi1) gene
      transfer sensitized H1299 and DLD-1 cells, presumably, through RARbeta
      upregulation. We also demonstrated the efficacy of intratumoral injection of
      Ad5CMV-p21 in combination with systemic administration of ATRA in a nude mice
      xenograft model. Our results indicate that recombinant adenovirus-mediated
      p21(sdi1) gene transfer could be potentially useful for the local induction of RA
      sensitivity in human premalignant and malignant lesions lacking appropriate
      RARbeta expression.

PMID- 12516109
TI  - [Elements of cytoskeleton and pathogenesis of allergic reactions. 1. Elements of
      cytoskeleton and their functions (a literature review)].

PMID- 12516110
TI  - [Changes in the cytological analysis of nasal secretions during a nasal
      secretion].
AB  - Changes of cytological parameters in the course of the nasal provocative test
      (NPT) we studied in 30 patients aged 14-43 years with chronic rhinitis of unknown
      etiology. Solutions of allergens in various concentrations were used for NPT and
      skin testing. NPT results were estimated clinically according to four-point scale
      and rhinocytogram 20 minutes after injection of different concentrations of
      allergens to nasal cavity. The results of the provocative tests coincide with
      case history data more frequently than skin test results. The discrepancy between
      anamnesis and results of skin tests in the group of patients reached 30.7%. A
      mean 8-fold increase in eosinophil count in nasal secretion was observed in
      patients with clinically confirmed NPT (76% cases) 20 minutes after injection of
      a minimal concentration of allergen extract to the nasal cavity. This eosinophil
      infiltration of nasal secretion preceded the occurrence of clinical symptoms. An
      unusual cytological picture of nasal secretion was observed in three patients
      with positive anamnestic data, results of skin testing and NPT. Eosinophil
      infiltration of nasal recreation was absent but neutrophil number increased.
      Increased eosinophil count on rhinocytogram after injection of allergen extract
      to nasal cavity can serve as an objective criterion of NPT. The described cases
      of neutrophil infiltration of nasal secretion testify to possible participation
      of these cells in acute allergic inflammation in patients with clinically
      positive NPT.

PMID- 12516111
TI  - [Automation of blood analysis with the hematologic system GEN-S].

PMID- 12516112
TI  - [Extrahospital pneumonia caused by S. pneumoniae in young patients].

PMID- 12516113
TI  - [Biological variations of analyte parameters in urea of patients examined at an
      outpatient facility].

PMID- 12516114
TI  - [Computer program "Enteroid+" for bacterial phenotypic identification and
      differentiation].

PMID- 12516115
TI  - [Apoptosis and its role in the regulation of cell equilibrium (a lecture)].

PMID- 12516116
TI  - [Control of preanalytical stage in a centralized laboratory].

PMID- 12516117
TI  - [Substantiation of quality control necessity in determination of phenotype of
      lymphocytes from peripheral blood and approaches to its realization].

PMID- 12516118
TI  - [Results of using intralaboratory quality control standards for laboratory
      tests].

PMID- 12516119
TI  - [Current status and problems of quality control in microbiological diagnosis in
      medical practice].

PMID- 12516120
TI  - [Progress in laboratory medicine and its realization in analytical technology
      (notes from the 21st World Congress of Pathology and Laboratory Medicine and the
      International Exhibition "Medica", Dusseldorf, 2001].

PMID- 12516122
TI  - [The assessment of the risk of the influence of environmental factors on health
      in the socio-hygienic monitoring system].

PMID- 12516123
TI  - [Methodological aspects of the evaluation of risk factors for population health
      in transient and chronic exposure to chemical substances polluting the
      environment].

PMID- 12516124
TI  - [Assessment of the risk of the influence of environmental factors as a
      constituent of the activities of the state sanitary and epidemiological service].

PMID- 12516125
TI  - [Carcinogenic risk to the population living in the areas of thermal and atomic
      power stations].

PMID- 12516126
TI  - [The pathogenetic peak rises on the average daily concentrations of suspended
      particles in the environmental air in populated locations].

PMID- 12516127
TI  - [Risk assessment in biomedical research].

PMID- 12516128
TI  - [The concept of risk factors in the system of measures ensuring sanitary
      epidemiological well-being].

PMID- 12516129
TI  - [The evaluation of contribution of motor transport exhaust to the integral
      characteristics of a risk of environmental air pollution].

PMID- 12516130
TI  - [Methodology for the assessment of a risk in the context of current tendencies in
      the management of chemical safety].

PMID- 12516131
TI  - [The assessment of the risk of exposure to air polluting chemicals in the
      populated areas and their impact on the population health].

PMID- 12516132
TI  - [Standardization of risk factor assessment].

PMID- 12516133
TI  - [Risk coefficients of non-carcinogenic effects].

PMID- 12516134
TI  - [The assessment of a risk to public health within the framework of global climate
      warming].

PMID- 12516135
TI  - [Problems in recurrent risk management].

PMID- 12516136
TI  - [Environmental factors influencing early aging and shorter longevity in Russia].

PMID- 12516137
TI  - [Risk assessment in the influence of environmental factors on the health of
      children and adolescents].

PMID- 12516138
TI  - [Clinical diagnosis of environmentally induced non-communicable diseases].

PMID- 12516139
TI  - [The use of methodology for the risk assessment during socio-hygienic monitoring
      in Moscow].

PMID- 12516140
TI  - [Regional aspects of carcinogenic risks in the agricultural-industrial region of
      the Southern Urals].

PMID- 12516141
TI  - [The assessment of individual risk to health: methodological aspects].

PMID- 12516142
TI  - [Problems in the assessment of risk for fluorine-dependent trace element
      poisoning].

PMID- 12516143
TI  - [Use of mathematical simulation models in health-environment systems].

PMID- 12516144
TI  - [Dependence of nonspecific bioeffects from air chemical pollutants in children].

PMID- 12516145
TI  - [Expertise in the testing and introduction of risk assessment methodologies].

PMID- 12516146
TI  - [A problem of stability and transformation in the comprehensive hygienic
      standardization of chemicals].

PMID- 12516147
TI  - [Morphological criteria for the risk of adverse influence of environmental
      factors on the body].

PMID- 12516148
TI  - [Determination of actual exposure levels to assess risks of pesticide effects on
      the workers' health].

PMID- 12516149
TI  - [The examination of antioxidative status in toxicological and hygienic assessment
      of genetically modified maize types].

PMID- 12516150
TI  - [Analyzing the work of state sanitary-epidemiological surveillance centers in
      risk assessment].

PMID- 12516151
TI  - [Organizational and methodical aspects of the use of a methodology for the
      assessment of risk in the practical activity of sanitary-epidemiological
      services].

PMID- 12516152
TI  - [Principles of the implementation of environmental health risk assessment in the
      socioeconomic management system].

PMID- 12516153
TI  - [Problems in staff training in environmental illness diagnosis].

PMID- 12516154
TI  - [Scientific-practical investigations on "Scientific bases of comprehensive risk
      assessment of the environmental effects on human health" in 2001].

PMID- 12516155
TI  - [Resolution of the Plenary Session of the Interdepartmental Research Council of
      Human Ecology and Environmental Hygiene "Assessment of the Risk of the Influence
      on Environmental Factors on Health Problems and Ways for Their Solution"
      (December 20-21, 2001, Moscow].

PMID- 12516156
TI  - Drugs, debates, deals, and deficits.

PMID- 12516157
TI  - Diligence in front-end processes is critical: an interview with Cheryl A. Harmon.
AB  - Cheryl Harmon's position reflects her organization's emphasis on an expanded role
      for the CFO. Harmon was hired recently to serve as CFO of Provena Covenant
      Medical Center, (PCMC) in Urbana, Illinois. Her mission as CFO is to help develop
      strategies to ensure that Provena Covenant maintains its financial stability.
      Harmon appreciates Povena Covenant's creative approaches to challenges faced by
      many healthcare organizations, such as workforce shortages.

PMID- 12516158
TI  - A financial argument for service-line management.
AB  - Service-line management is a management concept that focuses attention on
      specific segments of business within a hospital. Service-line management breaks
      down silos, fostering a team approach. Hospitals should use service-line
      management to grow strategically important services. Resources should be deployed
      appropriately. Hospitals should explore strategies for increasing volume of
      profitable services.

PMID- 12516159
TI  - Negotiating payment for new technology purchases.
AB  - The use of new technology in an existing healthcare service can have a far
      reaching impact on a hospital's financial health. An understanding of the
      financial impact of a service before new technology is added is helpful in
      preparing to negotiate for appropriate payment for the new technology. The
      indirect financial impact of new technology on related and unrelated healthcare
      services should be projected for use in managed care negotiations. Managed care
      payers seek proof of immediate savings when deciding on payment increases for new
      technology.

PMID- 12516160
TI  - Prompt payment depends on revenue-cycle diligence.
AB  - How effectively you manage the revenue cycle is reflected in the cycle's outcome
      whether you receive full and timely payment for all services billed to payers. To
      ensure prompt and full payment, you should: Educate your patient financial
      services (PFS) staff on all relevant laws and regulations regarding payment for
      healthcare services. Make sure your staff is well versed in all of the provisions
      of your payer contracts. Implement a state-of-the-art patient accounting system
      that is capable of producing drill-down reports of all aspects of contract
      performance by payer. Enforce payer compliance by maintaining complete records of
      dates of service, final billing dates, dates claims were mailed or electronically
      submitted to the payer, all actions performed by your staff regarding claims, and
      all communications with the payer.

PMID- 12516161
TI  - What CFOs should know--and do--about corporate responsibility.
AB  - Not-for-profit healthcare organizations are not immune to the scrutiny arising
      from corporate accounting scandals and legislation. Financial managers will play
      a critical role in satisfying corporate-responsibility concerns. Financial
      managers need to understand the public-policy concerns fueling the corporate
      responsibility movement and the effects. Financial managers should take steps
      related to certifying financial statements, establishing audit committees, and
      ensuring independence of audits, among other actions.

PMID- 12516162
TI  - 10 tips for avoiding APC traps.
AB  - To encourage proper payment and avoid imposition of penalties by the Office of
      Inspector General, providers need to prioritize outpatient compliance efforts.
      Departments should be accountable for reconciling outpatient code editor edit
      failures. Evaluation and management code assignment should be examined for inter
      rater reliability. Transitional pass-through items should be audited routinely;
      associated coding should be kept current. Consideration should be given to
      meeting medical necessity requirements, particularly for mental health services.

PMID- 12516163
TI  - Understanding variation in revenue and expenses.
AB  - Control charts offer a way for healthcare organizations to react appropriately to
      unexpected changes in performance indicators. Control charts demonstrate whether
      an immediate remedy or a redesign of a process is needed. An understanding of
      variation in processes can help in comprehending performance and avoiding
      identification of data trends that do not exist. Control charts can be used to
      more accurately estimate revenue and expenses over the long-term.

PMID- 12516164
TI  - Is your board financially savvy?

PMID- 12516165
TI  - Internet2: striking up the band for telemedicine.

PMID- 12516166
TI  - Data trends. The true cost of overtime.

PMID- 12516167
TI  - Old hat or cutting edge? The state of the art of clinical pathways.

PMID- 12516168
TI  - Comparative performance data can be change agent.

PMID- 12516169
TI  - CMSA overhauls case management standards.

PMID- 12516170
TI  - 'Hands-on' application tracks nursing care, results.

PMID- 12516171
TI  - 'Everybody wins' as CM, home health join forces.

PMID- 12516172
TI  - Patient safety alert. Construction brings opportunity to boost patient safety.

PMID- 12516173
TI  - Patient safety alert. Test interventions for improving safety.

PMID- 12516174
TI  - Informed consent and the elusive dichotomy between standard and experimental
      therapy.

PMID- 12516175
TI  - Coming of age: devising legislation for adolescent medical decision-making.

PMID- 12516176
TI  - The EPICC quest for prescription contraceptive insurance coverage.

PMID- 12516177
TI  - Adoption medicine and the internationally adopted child.

PMID- 12516178
TI  - How research will adapt to HIPAA: a view from within the healthcare delivery
      system.

PMID- 12516179
TI  - [Modes of reinforcement and gender and culture of experimenter and subject:
      effects of "alien" and external reinforcement for Japanese and American men and
      women].
AB  - In this study, we examined external and "alien" reinforcement (ER and AR.
      respectively) as a factor in social learning, and studied the combined effects of
      culture and reinforcement mode. A female (Experiment 1) and a male (Experiment 2)
      experimenters conducted experimental sessions. Both men and women, who grew up in
      the same culture as the experimenter, participated and performed the experimental
      task. A three-way interaction effect of experimenter gender, culture, and
      reinforcement mode was found on task performance. And the effect was more
      pronounced for a Japanese experimenter. A female and a male experimenters
      conducted Experiments 3 and 4, respectively; however participants this time were
      men and women who grew up in different cultures than the experimenter. Results
      indicated that the pattern of the subject gender and reinforcement mode
      interaction effect, when the experimenter was Japanese with American subjects,
      was exactly opposite to that when the experimenter was American. These
      experiments showed that AR was as effective for social learning as ER, and that
      the cultural backgrounds of experimenter and subject influenced AR and ER
      effectiveness.

PMID- 12516180
TI  - [Identification of familiar people viewed from a variety of viewpoints].
AB  - We investigated the visual information used to recognize human head from a
      variety of viewpoints. Subjects' task was to identify three familiar people from
      five different views (from the frontal face to the back of the head in steps of
      45 degrees). The mean reaction time (RT) was not affected with changing head
      angles when the image was original face version. RT significantly decreased when
      the images contained in high spatial frequency (SF) component. Moreover, there
      was an effective SF range in recognition from each viewpoint, which was the
      middle range for the frontal face and the higher range for the back of the head.
      For the profile, there was no change in RT across the ranges of SF. These results
      suggest that different view-specific information was used on each view for
      identification, and the recognition of the profile might be unique on familiar
      face processing.

PMID- 12516181
TI  - [Effects of imagery instructions on false memories produced on implicit and
      explicit memory tests].
AB  - In two experiments, we investigated whether the Deese-Roediger-McDermott paradigm
      using implicit and explicit memory tests would produce critical lure (CL) words.
      Participants studied lists of semantic associates (e.g., newspaper, book, write)
      to induce memories for CL words (e.g., read). Afterwards, participants
      participated in implicit and explicit memory tests in each experiment. The level
      of priming of the CL words was quite high and similar to that of the presented
      words when participants were instructed to image the interword relation on lists
      during study. Participants explicitly recognized many CL words as having been
      presented on the lists in Experiment 1 and recalled many CL words in Experiment
      2. The results are discussed in light of Underwood's (1965) implicit associative
      response hypothesis.

PMID- 12516182
TI  - [Development of the Conscious Defensiveness Questionnaire (CDQ)].
AB  - Conscious defensiveness has been found to mediate the relationship between
      hostility and coronary artery disease. In order to investigate the influence in
      Japan, the Conscious Defensiveness Questionnaire (CDQ) was developed and its
      validity and reliability were assessed in the present studies. The first study
      with college students (N = 419) was conducted to construct the CDQ as a 16-item
      questionnaire based on two preliminary researches. Factor analysis indicated that
      the 16 items in the CDQ conform to one factor structure, and the CDQ showed
      adequate factorial validity as well as high internal consistency. In the second
      study, the results of test-retest with college students (N = 225) revealed
      satisfactory stability of the CDQ over a 6- to 7-week period, and furthermore it
      showed construct validity in the relationships with peer ratings and nominations
      for college and graduate students (N = 191). Thus the present studies established
      the CDQ as a standardized questionnaire to measure conscious defensiveness.

PMID- 12516183
TI  - [An investigation of personal factors on daily stress of people with visually
      impairment].
AB  - In study 1, the test-retest reliability and concurrent validity of Stress Check
      List for the Visually Impaired (SCLVI) were investigated. Results demonstrated
      high reliability and validity. In study 2, multiple regression analysis was
      performed to examine the effects of personal factors on daily stress measured by
      SCLVI in 144 people with visually impairment. The predictors were: sex, age, age
      their eyesights were impaired, and whether or not the subjects have family
      members to live with; the dependent variables were 3 stress subscales. Results
      showed that "disturbing and conflicting stress" was lower among the older than
      among the younger visually impaired people. The visually impaired with higher
      eyesight levels felt higher stress in their interactions with people with normal
      eyesight. It was concluded that age and sight level among personal factors affect
      daily stress of visually impaired people significantly.

PMID- 12516184
TI  - [Effects of neighborhood size and kanji character frequency on lexical decision
      of Japanese kanji compound words].
AB  - The purpose of this study was to make a clear distinction between the effects of
      neighborhood size (Coltheart, Davelaar, Jonasson, & Besner, 1977) and that of
      kanji character frequency on the processing of two kanji compound words (jukugo).
      Kanji characters found in many compound words tend to be frequent, so
      neighborhood size of jukugo and the character frequency of the component kanji of
      these jukugo tend to be interrelated. In this study, the effect of neighborhood
      size on jukugo with medium subjective frequency was investigated controlling
      kanji character frequency. In an experiment using a lexical decision task with 30
      participants, neighborhood size, front kanji character frequency, and rear kanji
      character frequency of jukugo were manipulated. The results showed that both the
      neighborhood size and the kanji character frequency affected the lexical decision
      of jukugo. The fact that there was no interaction between front and rear kanji
      character frequencies suggests that front and rear characters of jukugo with
      medium frequency were processed in a serial fashion.

PMID- 12516185
TI  - [Computer mediated discussion and attitude polarization].
AB  - This study examined the hypothesis that computer mediated discussions lead to
      more extreme decisions than face-to-face (FTF) meeting. Kiesler, Siegel, &
      McGuire (1984) claimed that computer mediated communication (CMC) tended to be
      relatively uninhibited, as seen in 'flaming', and that group decisions under CMC
      using Choice Dilemma Questionnaire tended to be more extreme and riskier than FTF
      meetings. However, for the same reason, CMC discussions on controversial social
      issues for which participants initially hold strongly opposing views, might be
      less likely to reach a consensus, and no polarization should occur. Fifteen 4
      member groups discussed a controversial social issue under one of three
      conditions: FTF, CMC, and partition. After discussion, participants rated their
      position as a group on a 9-point bipolar scale ranging from strong disagreement
      to strong agreement. A stronger polarization effect was observed for FTF groups
      than those where members were separated with partitions. However, no extreme
      shift from their original, individual positions was found for CMC participants.
      There results were discussed in terms of 'expertise and status equalization' and
      'absence of social context cues' under CMC.

PMID- 12516186
TI  - [An analysis of the relationship between aggressiveness and personality traits of
      children].
AB  - The purpose of the present study was to understand the concept of aggressiveness
      of children through an analysis of the relationship between aggressiveness and
      personality traits. A total of 1,206 elementary school children were enrolled in
      the study. In order to investigate the correlation, a path analysis was performed
      using multiple regression analyses in which 4 variables of aggressiveness
      (irritability, hostility, physical aggression and verbal aggression) were
      employed as dependent variables and 5 variables of personality traits
      (agreeableness, conscientiousness, emotionality, openness and extroversion) were
      used as independent variables. The results of the analysis indicated that
      significantly positivepath was observed from extroversion to all four variables
      of aggressiveness. Extroversion indicated especially strong influence on
      irritability and physical aggression. A significantly negativepath was observed
      from agreeableness to irritability and hostility. From conscientiousness, a
      negative path was observed towards physical aggression and a positive path
      towards verbal aggression. A significantly negative path was observed from
      emotionality only towards verbal aggression. It was assumed that each of the four
      inferior characteristics of aggressiveness of children had a complex nature to be
      influenced by multiple personality traits.

PMID- 12516187
TI  - [Reactance proneness, collectivism, uniqueness, and resistance to persuasion].
AB  - This study examined the reliability and validity of Japanese psychological
      reactance scales. A total of 167 undergraduates completed a questionnaire of
      Therapeutic Reactance Scale (TRS), the Hong Reactance Scale (HRS), the Uniqueness
      Scale, and the Collectivism Scale. They also received messages involving three
      persuasion situations that were either high or low in terms of threat, and were
      asked to describe their reactions to them. The author categorized the reactions
      into three: acceptance, indirect resistance, and direct resistance. Reliabilities
      of the reactance scales were satisfactory. Their scores positively correlated
      with uniqueness scores, and negatively with collectivism scores. Those high on
      reactance proneness were less persuaded in two of the three situations. But in
      the third, an HRS by threat interaction was observed, indicating that only those
      who were high on reactance proneness under the high-threat condition showed
      resistance to persuasion. These results suggest that the Japanese versions of
      reactance scale were reliable and valid. However, the assertiveness aspect of TRS
      may not be appropriate for the definition of reactance. The influence of culture
      on psychological reactance was also discussed.

PMID- 12516188
TI  - [The expertise of an actor: script reading, performance planning, and actual
      performance].
AB  - In this study, we examined the expertise of actors, for which few studies have so
      far been conducted. Participants for the study, all male, were ten novice actors
      with less than one year experience, ten intermediate actors with experience of
      one to five years, and ten junior expert actors with more than five years of
      acting. The process of acting in a play was divided into three phases; script
      reading, performance planning, and actual performance. We asked some questions of
      participants in each phases, and analyzed video recording of their actual
      performance. Results suggested that novice actors had some difficulties in
      understanding the 'written' in the script. It was also suggested that in planning
      performance, the longer experience the actor had, the more things he could take
      into account, and the longer he spent for the preparation. Therefore, performance
      of junior expert actors was more diversified. Our findings also indicated that
      junior expert actors were more adept at expressing what they wanted to without
      being consciously aware of what they had actually to do.

PMID- 12516189
TI  - [Antibacterial prophylaxis of bacteriuria at transrectal multifocal prostatic
      biopsy].
AB  - It was shown that prophylactic use of ciprofloxacin (500 mg per os 30 min prior
      to and 5 days after transrectal multifocal prostatic biopsy) along with topical
      treatment with 40 ml 1% povidone-iodine and evacuant enema provided negative
      bacteriological urine analysis in 24 hours for 94.4 per cent of cases. Positive
      effect was registered for all patients as no urinary tract infections were
      demonstrated. Transitory fever over 37.5 degrees C was not registered at 67 (97.2
      per cent) patients, for the rest cases no changes of the treatment regime were
      necessary. The results of the trial proves high bacteriological and clinical
      efficacy of the therapy regimes and allow to recommend its implementation at
      transrectal biopsy.

PMID- 12516190
TI  - [Mechanisms of azithromycin accumulation and efflux in human polymorphonuclear
      leukocytes].
AB  - Azithromycin achieves prolonged, high tissue concentrations in spite of low serum
      levels and obviously must be effective at tissue sites of infection. These unique
      features prompted us to evaluate the interactions of azithromycin and human
      polymorphonuclear leukocytes (PMN). Uptake of radiolabeled antibiotic by PMN was
      determined by a velocity-gradient centrifugation technique and expressed as the
      ratio of cellular to extracellular drug concentration (C/E). Azithromycin was
      massively accumulated by human PMN (C/E = 387.2 at 2 h). Uptake was not
      influenced by inhibitors of cellular metabolism, but phagocytosis slightly
      inhibited the entry of azithromycin into PMN. After removal of extracellular
      drug, the release (efflux) of azithromycin from PMN was extremely slow. Agents
      which neutralize lysosomal pH, preventing protonation and trapping of
      azithromycin, markedly increased antibiotic efflux. Active concentration and
      prolonged retention of azithromycin by phagocytic cells should allow delivery and
      subsequent release of accumulated drug at sites of infection.

PMID- 12516191
TI  - [Benzylpenicillin efficacy for neutropenic infection prophylaxis in patients with
      cancer and postcytostatic neutropenia].
AB  - Evaluation of benzylpenicillin (penicillin G) effect for infection prophylaxis at
      the oncological patients with severe postcytostatic neutropenia was performed.
      All the patients with neutrophils levels lower than 0.5 x 10(9)/L were
      recommended to use antibiotics for infection prophylaxis. Test-group (n = 40)
      used ciprofloxacin (0.5 g twice daily, per os) combined with benzylpenicillin
      (1.0 g four times daily, i/v); control group was treated by ciprofloxacin in the
      same dose only. Combination with benzylpenicillin resulted in statistically
      significant reduction of infections frequency among oncological patients.

PMID- 12516192
TI  - [Problems and perspectives of antibiotics application in rheumatological
      patients].

PMID- 12516193
TI  - [Use of ciprofloxacin in sequential antibiotic therapy].

PMID- 12516194
TI  - [Antibacterial therapy of pneumococcal infections caused by drug resistant
      microorganisms].

PMID- 12516195
TI  - [Linezolid--new antibacterial agent of the oxazolidinone group: its importance in
      the control of spreading and treatment of the multidrug resistance gram-positive
      infections].

PMID- 12516196
TI  - The liver in obesity and type 2 diabetes mellitus.
AB  - Obesity and type 2 diabetes are associated strongly with NAFLD. It is not clear
      if one of these conditions causes the others, or if all are consequences of
      another process. Although NAFLD is known to occur in overly lean individuals,
      which indicates that excessive adiposity is not required for the development of
      NAFLD, the severities of insulin resistance and NAFLD tend to parallel each
      other, and the greatest prevalence of type 2 diabetes occurs in patients with
      NAFLD and cirrhosis. This observation suggests that insulin resistance and NAFLD
      may be related pathogenically. Experiments in mice demonstrate that insulin
      resistance and NAFLD result from a chronic inflammatory state that is
      characterized by increased levels of TNF alpha. The mechanisms that drive this
      chronic inflammation are unknown but might involve the oxidative stress that
      develops during fatty acid metabolism or when products from intestinal bacteria
      escape into the mesenteric blood to trigger a sustained hepatic inflammatory
      cytokine response in genetically susceptible individuals, promoting a positive
      feedback loop that reinforces insulin resistance and inflammation. This
      hypothesis is supported by some animal and human studies; however, more research
      is needed to evaluate this theory. Additional studies also are required to
      determine the benefits of treatments that interrupt this pathogenic cascade at
      various points. Preliminary work in animal and human studies suggests that
      diverse strategies that inhibit production of TNF alpha and improve insulin
      resistance also ameliorate NAFLD.

PMID- 12516197
TI  - The liver in other (nondiabetic) endocrine disorders.
AB  - The liver has a major role in the proper maintenance of intermediate metabolism
      and endocrine homeostasis. It contains enzymes that are essential for hormonal
      biotransformation and the regulation of numerous metabolic reactions, which
      control hormone metabolism. The liver also manufactures several proteins, which
      carry circulating hormones to their effector sites. The endocrine system exerts
      tight control of the metabolic reactions within the liver, which also can be
      disturbed by endocrine disorders. These types of interactions and the effects of
      the exogenous hormones and the drugs that are used as treatment for hormonal
      disorders are discussed.

PMID- 12516198
TI  - Anemia and the liver. Hepatobiliary manifestations of anemia.
AB  - Many types of hemolytic anemia may be associated with liver disease. Liver injury
      can be caused by the adherence of deformed or hemolyzed erythrocyses to hepatic
      vascular endothelium. Adhesion of large numbers of hemolyzed red blood cells to
      hepatic macrophages, or occlusion of hepatic sinusoids by fragmented red cells,
      can also result in injury of the liver. Thrombosis of the hepatic or portal vein
      is associated with some types of hemolytic anemia, and can cause severe liner
      injury. These are some examples of hepatic injury that can be caused by hemolytic
      anemias. This article discusses some aspects of liver disease that is associated
      with sickle cell anemia, paroxysmal nocturnal hemoglobinuria, glucose-6-phosphate
      dehydrogenase deficiency, hereditary spherocytosis, and HELLP syndrome.

PMID- 12516199
TI  - Hepatic circulatory diseases associated with chronic myeloid disorders.
AB  - These liver diseases are diseases of the hepatic circulation. Myeloproliferative
      disorders are among the most common prothrombotic disorders that lead to Budd
      Chiari syndrome and PVT. SOS, previously known as hepatic veno-occlusive disease,
      is mainly seen in North America and Western Europe as a complication of the
      conditioning regimen for hematopoietic stem cell transplantation. SOS is caused
      by damage to SECs, and the initiating circulatory blockage occurs because of the
      embolism of sinusoidal lining cells. Myeloproliferative disorders are an uncommon
      cause of NRH, which is believed to be caused by uneven perfusion of the liver at
      the venous or sinusoidal level. Peliosis hepatis is believed to result from
      damage to SECs and is seen mainly in immunosuppressed patients, patients with a
      wasting illness, or patients with a drug toxicity.

PMID- 12516200
TI  - Liver abnormalities in rheumatic diseases.
AB  - Abnormalities of LFTs and liver function occur not infrequently in patients with
      rheumatic conditions, and many diagnostic possibilities exist. Systemic
      inflammation that is related to uncontrolled rheumatic disease and periods of
      disease remission have been described as a cause for fluctuations in levels of
      serum aminotransferases. Although these benign extra-articular manifestations of
      rheumatic disease are the most common manifestations, more serious hepatic
      involvement, including vasculitis, nodular regenerative hyperplasia, and primary
      biliary cirrhosis, have been observed in specific rheumatic diseases. The cause
      of rheumatic disease is unclear. Occult HCV infection and associated
      cryoglobulinemia can mimic rheumatic disease. HCV infection should be suspected
      routinely in patients with mixed cryoglobulinemia, especially because antiviral
      therapy may be beneficial. The medical management of rheumatic disease involves
      medications that are often hepatotoxic. Routine laboratory monitoring, imaging
      studies, and, if necessary, biopsy examination in situations in which serum
      aminotransferases remain abnormal, are recommended.

PMID- 12516201
TI  - The liver in heart failure.
AB  - Severe congestive heart failure is associated with two distinct forms of liver
      dysfunction: jaundice that is related to passive congestion and acute
      hepatocellular necrosis that is caused by impaired perfusion. Cardiac cirrhosis
      (fibrosis) may result from prolonged recurrent congestive heart failure. Ischemic
      hepatitis (shock liver) usually manifests as asymptomatic elevation of the serum
      aminotransferase levels after an episode of hypotension, although the clinical
      presentation may mimic that of acute viral hepatitis. In most cases, ischemic
      hepatitis is of little clinical consequence and is self-limited. Acute liver
      failure may occur in patients with preexisting cirrhosis, severe chronic heart
      failure, or sustained hepatic ischemia.

PMID- 12516202
TI  - Hepatic manifestations of pulmonary diseases.
AB  - Pulmonary complications from chronic liver disease are well known and include
      hepatopulmonary syndrome, hepatic hydrothorax, and pulmonary hypertension. This
      article reviews the hepatic complications of diseases that are primarily
      pulmonary diseases. The authors focus on alpha 1 antitrypsin deficiency, an
      autosomal recessive metabolic disorder that can affect the lungs, liver, kidneys,
      and pancreas; sarcoidosis, a systemic disease of unknown origin that can affect
      multiple organs; and cystic fibrosis, an autosomal recessive disease that affects
      the lungs, exocrine pancreas, liver, and intestines.

PMID- 12516203
TI  - Liver and kidney diseases.
AB  - The spectrum of renal disease in patients with liver disease is expanding. The
      recognition of renal complications of liver diseases is essential in the
      management of these patients. As liver transplantation is a treatment option for
      many patients with chronic liver disease, the presence of renal complications
      impacts the decision regarding transplantation and influences the course of these
      patients after transplantation, especially with regard to the use of
      immunosuppressive therapy. The involvement of the liver and kidney in systemic
      conditions is common and adds to the morbidity and mortality of patients.

PMID- 12516204
TI  - Hepatic manifestations of gastrointestinal diseases. Inflammatory bowel disease,
      celiac disease, and Whipple's disease.
AB  - The gastrointestinal tract and the liver are closely related anatomically,
      physiologically, and pathologically. Some disease associations are well
      documented, such as PSC in association with IBD, whereas others are less well
      defined. A heightened clinical suspicion is required in these patients who do not
      present with the classical disease associations. The underlying causes of their
      diseases are the subject of much debate and research, and their diagnosis and
      management remain challenging.

PMID- 12516205
TI  - Liver involvement in patients with solid tumors of nonhepatic origin.
AB  - Metastatic disease represents the most common hepatic neoplasm in the Western
      world. The most common primary malignancies to spread to the liver are those that
      originate in the gastrointestinal tract. Of non-gastrointestinal malignancies,
      breast, lung, and melanoma malignancies are most likely to develop hepatic
      metastases. Some solid tumors, such as renal cell carcinoma, may cause liver
      related abnormalities in the absence of hepatic metastases, presumably by way of
      cytokine-mediated mechanisms. Physical examination, laboratory testing,
      histologic evaluation, and various radiographic studies are useful in the
      detection and diagnosis of liver metastases. Multiple treatment modalities are
      available, including hepatic resection, hepatic arterial chemotherapy, systemic
      chemotherapy, chemoembolization, cryotherapy, ethanol injection, and
      radiofrequency ablation.

PMID- 12516206
TI  - Liver in sepsis and systemic inflammatory response syndrome.
AB  - In patients with sepsis and SIRS, the liver has two opposing roles: a source of
      inflammatory mediators and a target organ for the effects of the inflammatory
      mediators. The liver is pivotal in modulating the systemic response to severe
      infection, because it contains the largest mass of macrophages (Kupffer cells) in
      the body; these macrophages can clear the endotoxin and bacteria that initiate
      the systemic inflammatory response. This article summarizes the functional
      changes that take place in the liver during sepsis and systemic inflammatory
      response syndrome and discusses the cellular and molecular mechanisms that
      underlie clinical outcomes.

PMID- 12516207
TI  - Postoperative jaundice and total parenteral nutrition-associated hepatic
      dysfunction.
AB  - Postoperative jaundice and TPN-induced hepatic abnormalities represent clinical
      situations that stem from multiple and frequently overlapping insults to the
      liver. The pattern of LFT abnormalities and appropriate imaging studies provide
      clues to the diagnosis. Greater insight into the molecular basis of cholestasis
      has shed light on the possible common pathways for the hepatic derangements that
      are seen in diverse situations. TPN-related hepatic dysfunction most likely
      involves a combination of nutritional deficiencies, hormonal imbalances,
      excessive calories, and possibly bacterial overgrowth in the small bowel. Growing
      clinical evidence points to a high incidence of severe liver disease in chronic
      TPN-dependent patients. Careful monitoring of patients is warranted in these
      circumstances and combined transplantation of the liver and small bowel may be
      the only possibility for long-term survival for such patients with progressive
      liver disease.

PMID- 12516208
TI  - Computer simulations and neutron reflectivity of proteins at interfaces.
AB  - Computer simulations in conjunction with neutron reflectivity is an excellent
      combination for the study of biological materials at solid-liquid interfaces:
      Both techniques have excellent resolution levels (Angstroms) and they are mature.
      A stronger interaction between physicists and biologists will allow the use of
      these two approaches in topics of biological-biomedical interest.

PMID- 12516209
TI  - What does elementary chirality have to do with neutrinos?

PMID- 12516210
TI  - Excitation energy transfer in dendritic host-guest donor-acceptor systems.
AB  - We report on a study of a physically formed host-guest system, which was designed
      to be investigated by fluorescence energy transfer. All donor and acceptor
      molecules used were cyanine dyes. Investigation was performed at the ensemble
      level as well as at the single-molecule level. The ensemble measurements revealed
      a distribution of binding sites as well for the donor as for the acceptor.
      Accordingly, we found a distribution of the energy transfer efficiency. At the
      single-molecule level, these distributions are still present. We could
      discriminate entities that show very efficient energy transfer, some that do not
      show any energy transfer and systems whose energy transfer efficiency is only
      about 50%. The latter allowed the time-resolved detection of energy transfer of
      single entities through the acceptor decay. Finally, we discuss the observation
      that the energy transfer efficiency fluctuates as a function of time.

PMID- 12516211
TI  - Singlet energy transfer as the main pathway in the sensitization of near-infrared
      Nd3+ luminescence by dansyl and lissamine dyes.
AB  - In general, sensitization of lanthanide(III) ions by organic sensitizers is
      regarded to take place via the triplet state of the sensitizers. Herein, we show
      that in dansyl- and lissamine-functionalized Nd3+ complexes energy transfer
      occurs from the singlet state of the sensitizers to the Nd3+ center. No
      sensitized emission was observed in the corresponding complexes with Er3+, Yb3+,
      and Gd3+ ions. Furthermore, the fluorescence of the sensitizers was quenched only
      in the Nd3+ complex and not in the complexes with the other ions. Only Nd3+
      centers can accept energy from the singlet state of the dyes, because the excited
      states of Nd3+ have a high spectral overlap with the fluorescence of the dansyl
      and lissamine sensitizers, and because the selection rules allow a fast energy
      transfer, which apparently is competitive with the fluorescence.

PMID- 12516212
TI  - Surface electromigration patterns in a confined adsorbed metal film: Ga on GaN.
AB  - The mass transport of gallium adatoms in a confined gallium bilayer on GaN(0001)
      is studied with photoelectron spectromicroscopy with the goal to identify the
      diffusing species and their lateral distribution during directional surface
      electromigration and/or "random" thermal diffusion. It has been found that only
      the gallium atoms from the second layer undergo biased diffusion involving
      formation of three-dimensional islands. The development of different gallium
      concentration patterns is described by means of a general model, considering the
      presence of vacancies and trapping centres for the diffusing atoms.

PMID- 12516213
TI  - Cubic mesophase in an unsymmetrical alkyl ammonium salt. Synthesis and structural
      model.
AB  - N,N,N-butylethylpentylpropylammonium iodide 4 and related molecules have been
      selectively synthesised from commercially available aldehydes, amines and alkyl
      iodides using a reductive alkylation procedure. The crystalline texture of 4
      obtained on cooling is optically isotropic between crossed polarisers, indicating
      a cubic structure. Differential scanning calorimetry (DSC, +10 K min-1) reveals a
      glass phase transition at -59 degrees C and a melting point at 192 degrees C. The
      melting entropy (23.9 J mol-1 K-1) indicates a first-order transition between a
      highly disordered mesophase and the isotropic liquid. Powder X-ray diffraction
      patterns were indexed in the cubic system (a = 14.08A; Pm3n space group). In this
      cell, the molecular packing with Z = 6 corresponds to a rather low compactness of
      65%. Iodine and tetraalkylammonium ions occupy positions with a 4m2 site
      symmetry. These highly symmetrical states may be generated by stepwise rotation
      of the ammonium cation. The same structural model for orientationally disordered
      crystal (ODIC) phases can be applied to a series of tetraalkylammonium bromides
      and iodides.

PMID- 12516214
TI  - AFM, X-ray diffraction and optical microscopy studies of faceted droplets of a
      thermotropic bicontinuous cubic mesophase.

PMID- 12516215
TI  - Quantum transport effects in nanosized graphite sheets.

PMID- 12516216
TI  - Solid-state fingerprints of molecular threading detected by inelastic neutron
      scattering.

PMID- 12516217
TI  - Two-dimensional self-assembly of liquid-crystalline perylene diimide derivatives
      at the air/water interface.

PMID- 12516218
TI  - A comparative investigation of spin crossover in bulk materials, lamellar CdPS3
      layers, and polyelectrolytes in a series of ferric complexes: [FeIII((X
      sal)2trien)]Y.

PMID- 12516219
TI  - Quality-based incentives continue gaining ground.

PMID- 12516220
TI  - How capitated groups use hospitalists to reduce inpatient costs, boost profits.

PMID- 12516221
TI  - California IPA struggling to overcome capitation shortfalls.

PMID- 12516222
TI  - Use common sense approach to managing emergency risk.

PMID- 12516223
TI  - Disability status differentials across fifteen Asian and Pacific Islander groups
      and the effect of nativity and duration of residence in the U.S.
AB  - This study examines disparities in disability status across 15 Asian and Pacific
      Islander American (API) subpopulations and how nativity and duration in the U.S.
      influence these differences. Employing three disability questions (work
      limitations, mobility limitations, and self-care limitations) from the 1990 PUMS,
      the authors find substantial heterogeneity in disability status across API
      subgroups: while Japanese American adults have the most favorable outcomes, Other
      Southeast Asian adults (Laotians, Hmong, and Cambodians), followed by Vietnamese
      and Pacific Islander adults, suffer from a high risk of disabilities. Many of the
      disparities in disability status across API subpopulation adults are attributable
      to differentials in demographic characteristics and SES. The inclusion of an
      interaction term of age and nativity/duration of residence in the U.S. in
      multivariate regression analyses demonstrates that the effect of
      nativity/duration plays a different role across age, net of demographic, and SES
      risk factors. The overall findings are also consistent with previous studies on
      the relationship between immigrant health and nativity/duration. That is,
      immigrants with short duration in the U.S. have superior health status, measured
      by risk of disability, than longer-term immigrants and their U.S.-born
      counterparts.

PMID- 12516224
TI  - Changes in the association of low birth weight with socioeconomic status in
      Hawaii: 1970-1990.
AB  - This study examines rates of low birth weight (LBW) in the state of Hawaii and
      changes in the association of LBW with socioeconomic status from 1970 to 1990.
      The analysis is based on aggregate data for census tracts. Rates of low birth
      weight were calculated for each census tract. Relative socioeconomic scores were
      calculated from average household income and years of education. The results show
      that (1) there was a decrease in the rate of low birth weight infants in Hawaii;
      and (2) that the correlation between socioeconomic status and low birth weight
      was substantially reduced, though a significant correlation remains. The paper
      suggests likely ceiling effects, but that the progressive public health policies
      and expansion of access to primary health care in Hawaii during this period
      played a major role in reducing the rate of low birth weight infants and in
      decreasing socioeconomic inequality on this important health indicator.

PMID- 12516225
TI  - Pregnancy wantedness: attitude stability over time.
AB  - In this analysis we have compared two attitudinal reports, from interviews two
      years apart, of the same event for consistency over time. We have looked at
      women's self-reports, and at their proxy reports for partners' attitudes as well.
      The inconsistent reports of women's own views tended to shift slightly toward
      more favorable reports at the second interview (15 percent more positive versus
      10 percent more negative). More specifically, 7.5 percent of women who reported
      at Time 1 that their most recent births had been unwanted switched to more
      favorable reports at Time 2, and about the same percentage of women who reported
      Table 4, the findings would suggest that some of the groups typically considered
      to be most "at risk" were those who were also most apt to report inconsistently.
      This findings should signal some concern in the policy community. Net of other
      factors, there is no effect of income, but a number of at-risk groups remained
      significantly more likely than others to change their reports over time. Of
      particular concern is the finding that women who reported their pregnancies as
      mistimed or unwanted were so much more likely to change their reports over time
      than were women who initially said that their pregnancies had been well timed.
      When we look at the direction of change, it is clear that, with some exceptions,
      the more "at risk" groups were more likely to shift in a more negative direction,
      while the less "at risk" groups were less likely to do so; and at times they were
      more likely to report more favorably at the second interview. Although somewhat
      hampered by small sample sizes in the analysis of Time 1 mistimed and unwanted
      reports, results confirmed that certain subgroups were not only more apt to
      report inconsistently, they were also more likely to do so in specific
      directions. To the extent that future survey questions can emphasize to
      respondents that they should focus on the time of conception, and not on current
      status, inconsistency across groups may be reduced.

PMID- 12516226
TI  - Condom use and partner characteristics among young adult males in urban Ghana,
      aged 15-24.
AB  - Addressing male sexual behavior and condom use is a high priority for adolescent
      health programs. Using the 1997 Ghana Psychographic Survey, the aim of this study
      is to explore the factors related to current, partner-specific condom use, by
      Ghanaian males aged 15-24 years. A multivariate regression analysis reveals an
      independent association between psychographic attitudes, peer network
      characteristics, sexual partner characteristics, and some level of condom use
      with a nominated sexual partner. The most important predictor for both condom use
      consistently as well as condom use at least sometimes was respondents' knowing
      someone who died as a result of AIDS. This finding suggests that future
      interventions should aim to personalize the risk of HIV/STIs, promote condom use
      with a range of partner types, and educate youth about the importance of
      consistent use.

PMID- 12516227
TI  - Motivational antecedents to contraceptive method change following a pregnancy
      scare: a couple analysis.
AB  - In this study we develop and then test a couple model of contraceptive method
      choice decision-making following a pregnancy scare. The central constructs in our
      model are satisfaction with one's current method and confidence in the use of it.
      Downstream in the decision sequence, satisfaction and confidence predict desires
      and intentions to change methods. Upstream they are predicted by childbearing
      motivations, contraceptive attitudes, and the residual effects of the couples'
      previous method decisions. We collected data from 175 mostly unmarried and
      racially/ethnically diverse couples who were seeking pregnancy tests. We used
      LISREL and its latent variable capacity to estimate a structural equation model
      of the couple decision-making sequence leading to a change (or not) in
      contraceptive method. Results confirm most elements in our model and demonstrate
      a number of important cross-partner effects. Almost one-half of the sample had
      positive pregnancy tests and the base model fitted to this subsample indicates
      less accuracy in partner perception and greater influence of the female partner
      on method change decision-making. The introduction of some hypothesis-generating
      exogenous variables to our base couple model, together with some unexpected
      findings for the contraceptive attitude variables, suggest interesting questions
      that require further exploration.

PMID- 12516228
TI  - Alternative theories of the relationship of schooling and work to family
      formation: evidence from Mexico.
AB  - Role incompatibility, education as an investment in human capital, and schooling
      as a transformative experience are three mechanisms that link women's education
      to the timing of marriage and first birth. We simultaneously evaluate these
      different explanations using retrospective life history data for two cohorts of
      Mexican women collected in a nationally representative sample. Our analyses
      provide evidence in support of all three hypotheses. While in school young women
      are at a substantially lower risk of marriage and of a first birth. We find no
      evidence that women leave school to enter into unions nor do we find evidence
      that the effect of being a student diminishes with age. Women who work for a wage
      are also at a lower risk of marriage and a first birth. Once we control for
      student and employment status, the direct effects of cumulative education on
      family formation are relatively modest, although cumulative education is strongly
      associated with positive attitudes towards women's work and a significant
      increase in the likelihood of premarital and postmarital employment.

PMID- 12516229
TI  - The biosocial female choice theory of social stratification.
AB  - For decades, the study of social stratification has been dominated by
      environmental theories. Herein a theory is proposed that contains both biological
      and sociocultural elements. The theory asserts that most human females, like
      females of many other mammalian species, have evolved mating preferences biased
      toward males who are competent in provisioning resources. This female bias is
      hypothesized to have been naturally selected because females with these biases
      nearly always have had a reproductive edge over females who lack such a bias. One
      result of this bias is that human females preferentially mate with males who
      strive to rise in social status. This, in turn, has favored males who attain or
      at least strive for high social status, and who advertise and even exaggerate
      whatever status they already have achieved. At the genetic level, the theory
      postulates that alleles have accumulated on the human genome that promote social
      status-striving and achievement to varying degrees. To account for why males are
      more prone toward status-striving than females, the theory contends that one or
      more genes on the Y-chromosome interact with genes on the remaining human
      chromosomes to incline males to gravitate toward social hierarchies and to strive
      for niches that are relatively high in those hierarchies. Both tested and
      untested hypotheses are derived from the theory and compared to the empirical
      evidence currently available.

PMID- 12516230
TI  - Why single men might abhor foreign cultures.
AB  - In contrast to cues to women's mate value (youth and physical attractiveness),
      many qualities that men display in lekking are socially and culturally specific.
      We predict that, for this reason, men avoid exposure to foreign cultures, but
      such xenophobia should cease once they are married (especially since the presence
      of their wives can function as a cross-culturally meaningful lekking device).
      Analyses of data from Europe and the United States confirm our predictions.

PMID- 12516231
TI  - Where biodemographic theory and demographic data meet: a review of the Quest for
      Immortality (by Olshansky and Carnes). Essay review.

PMID- 12516232
TI  - [Exogenous nitric oxide and gallbladder contractility in humans].
AB  - The physiological function of the gallbladder (GB) is to deliver concentrated
      bile to the duodenum after a meal. This requires a complex coordination of the
      motor, secretory, and absorptive functions of the gallbladder. Control of GB
      motor functions involves a constant interplay between a large number of
      stimulatory and inhibitory hormones and neurotransmitters. With regard to
      intrinsic neurotransmitters, nitric oxide (NO) acts as a neurotransmitter in
      nonadrenergic, noncholinergic (NANC) pathways of the gallbladder. This compound
      has been found to inhibit GB tone and contraction in both animal and human
      studies. The Purpose of the present study was to examine the effects of exogenous
      NO donors such as glyceryl trinitrate (GTN), molsidomine (MO) and L-arginine (L
      Arg) on fasting GB volume and on meal-stimulated gallbladder contraction
      expressed as ejection fraction (EF). The healthy subjects (13 men and 17 women),
      age range 19-41 years participated in this study. GB volume was examined by means
      of an ultrasonographic method. Volumes of GB were calculated using the sum of
      cylinders method as described by Dodds. EF was measured every 15 min up to a
      total observation period of 2 h. After recording of control values, 0.5 mg GTN
      was administered sub-lingually, or 4 mg MO orally or L-Arg (12.63 g of L-Arg in
      300 ml of 0.9% NaCl) was infused i.v. over 120 min. It was found that the fasted
      GB volume was increased after GTN by 22 +/- 10% and after MO by 28 +/- 4% (p <
      0.05). Post-prandial EF was reduced maximally by 22 +/- 9% (p < 0.05) after
      pretreatment with GTN and by 32 +/- 8% (p < 0.01) after MO. Whereas L-Arg was
      without any effect on resting GB, however it reduced significantly stimulated EF.
      These findings support the earlier knowledge that NO, released from its exogenous
      donors has the potent inhibitory effect on human gallbladder motor activity.

PMID- 12516233
TI  - [Bacterial flora of hypertrophied tonsils in children with secretory otitis
      media].
AB  - The potentially pathogenic bacteria: Haemophilus influenzae, Moraxella
      catarrhalis, Streptococcus pneumoniae are the major bacterial flora of
      hypertrophied tonsils. In children suffering from otitis media with inflammatory
      effusion an unfortunate decreased physiological flora of Streptococcus viridans
      and Neisseria is observed.

PMID- 12516234
TI  - [Post-thyroidectomy hemorrhage].
AB  - The aim of the study was to estimate the prevalence and causes of haemorrhages,
      that required extemporaneous surgical treatment, after goiter operations, in our
      own material. Between 1984 and 2000, i.e. during 17 years, 7400 patients were
      operated in our Clinic due to different kinds of goiter. Haemorrhage during post
      operative period was presented in 46 (0.62%) patients. There were 37 women and 9
      men in the analysed material. The age of patients was between 19 and 77 years,
      and the average age was 50.6 +/- 15.4. The lowest percentage of this complication
      was observed after operation of non-toxic goiter (0.39%) and the highest in a
      group of patients operated due to Graves-Basedow's disease (1.02%). Frequent
      local symptoms were observed, such as: enlargement of circumference of neck,
      supple haematoma with dyspnoea, and sometimes swallowing difficulties. A decrease
      in blood pressure was observed in 5 (10.9%) patients. Low molecular weight
      heparin prophylaxis was applied in 18 (39.1%) patients and in 2 cases disorders
      of blood coagulability were observed. The quantity of drainage from the wound was
      between 30 and 610 ml, with average 249.8 +/- 144.69 ml. Time from main operation
      termination to revision was 20 to 1440 minutes, with average time 346 +/- 285.66
      minutes. The most common cause of post-thyroidectomy haemorrhage was bleeding
      from the thyroid lobe stump, which presented in 28 (60.9%) patients. The most
      dangerous haemorrhage, because of its intensity, was the bleeding from the upper
      thyroid artery (6 patients). During the postoperative period 16 patients (34.8%)
      required blood transfusions, however massive transfusions (4 and more blood
      units) were performed only in 4 patients. Early complications included: paralysis
      of recurrent laryngeal nerve in 6 patients and transient hypocalcaemia in one
      patient.

PMID- 12516235
TI  - [Thyrotoxicosis in heart recipients].
AB  - Between 1992 and 2000 in the group of the patients before heart transplantation,
      amiodarone induced thyrotoxicosis occurred in 5 (4 male and 1 female, average age
      45.5 years) patients. In four of the patients of that group orthotopic heart
      transplantation was done. Postoperative period in the patients with euthyreosis
      was uncomplicated. One patient died after HTx because of thyroid crisis.

PMID- 12516236
TI  - [Magnesium and calcium contents in hair and serum of children and young people
      with osteocopic-joint muscular pains of unknown origin].
AB  - The study included children and young people with osteocopic-joint-muscular pains
      of unknown origin, in whom calcium-magnesium disorders administration were
      suspected. It was found that the contents of magnesium and calcium in hair were
      lowered in relation to the healthy children, particularly in the youngest age
      group (up to 5 years old, significant difference at p < 0.10) and in children at
      the stage of development (11-15 years old, p < 0.05). In some children (N = 52)
      serum magnesium and calcium levels were additionally examined. The decreased
      magnesium and calcium levels in hair at their normal concentrations in serum were
      found considerably more often than the reverse situation.

PMID- 12516237
TI  - [Results of shoulder anterior instability treatment with Bankart procedure].
AB  - The goal of the study was to analyse the results of 16 open Bankart
      reconstructions performed with Mitek GII anchors in recurrent anterior shoulder
      instability. Assessment of results was based on Constant and Rowe scales. Mean
      result in Constant scale was 93.82 and in Rowe scale 85.9 points. No instability
      was found after the operation in this group. Open Bankart procedure with Mitek
      GII anchors is effective in treatment of recurrent anterior shoulder instability
      while shoulder arthroscopy is very a useful preemptive diagnostic procedure.

PMID- 12516238
TI  - [Evaluation of selected parameters of blood coagulation and the fibrinolysis
      system in patients undergoing total hip replacement].
AB  - Patients undergoing orthopedic surgery, particularly total hip replacement
      procedure belong to a group of patients with a high risk of thromboembolic
      complications. Postoperative deep vein thrombosis may occur in 40-80% of these
      patients. 4-19% of patients develop clinically evident pulmonary embolism and
      approximately 7% of cases in this group result in death. A thorough evaluation of
      coagulation disorders in the perioperative period could lead to detecting risk
      factors of thromboembolic complications development and could facilitate more
      effective prophylaxis management. The aim of the study was to evaluate the
      dynamics of selected blood coagulation and fibrinolysis parameters in patients
      undergoing total hip replacement surgery. The study included 66 patients
      undergoing total hip replacement surgery. The group consisted of 51 women and 15
      men, within the age range of 47-78, the mean age was 64. In 32 (group A) patients
      surgery was performed with the use of normovolemic hemodilution, in 34 (group B)
      the hemodilution procedure was not applied. The patients received low molecular
      heparin as prophylaxis started 12 hours prior surgery and continued for 5 weeks
      after. The examination of the coagulation system was performed: in the morning on
      the day of the operation--examination 1, on the day of the operation in the
      evening--examination 2, and on the first day after operation--examination 3. We
      determined the concentrations of thrombin-antithrombin complexes (TAT),
      prothrombin fragments 1 + 2 (F1 + 2), D-dimers (DD) and plasminantiplasmin
      complexes (PAP). In all the patients an ultrasound examination of the lower limbs
      by Doppler method was performed before the surgery and 10-12 days after the
      procedure. Significant activation of coagulation and fibrinolysis was found in
      all patients before surgery. 12 hour after the procedure a progressive increase
      of coagulation disorders was observed. After 24 hours marked decrease of
      coagulation parameters was noted. In group A significantly less thromboembolic
      complications was observed. On the basis of the performed examinations the
      following conclusions were drawn. (1) during total hip replacement surgery and
      particularly during the period of the first 12 hours after procedure, marked
      activation of coagulation and fibrinolysis occurred. (2) the application of the
      hemodilution procedure does not influence significantly the degree of coagulation
      and fibrinolysis disorders in the perioperative period.

PMID- 12516239
TI  - [Thyroid peroxidase antibodies and thyroid diseases in children and adolescents
      with newly diagnosed type I diabetes].
AB  - The objective of the authors was to evaluate the prevalence of TPO Ab and thyroid
      diseases in children with newly diagnosed type 1 diabetes. The examination
      included 153 patients (85/55.6% girls) from southeast Poland aged 11 months to do
      17.4 years (mean age 9.5 +/- 3.9 years). Apart from clinical assessment, all
      children had determinations made of serum TPO Ab, FT4 and TSH, while thyroid
      ultra sound was performed in each patients with abnormal thyroid morphology
      and/or positive TPO Ab titter. Positive TPO Ab was detected in 45 patients
      (29.4%). In this group 26 had isolated serum TPO Ab elevation, 18 had Hashimoto's
      disease, 1 Graves's disease. Another 12 children (7.8%) were demonstrated to have
      euthyroid goiter. Thyroid abnormalities were thus seen in 37.2% children with
      newly diagnosed type 1 diabetes. No association was demonstrated between the
      prevalence of thyroid abnormalities and sex. Children with subclinical stage of
      autoimmune thyreoiditis were significantly younger in comparison to patients with
      Hashimoto's disease (8.9 +/- 4.2 vs. 12.0 +/- 3.1 years) and had significantly
      lower serum TPO Ab and TSH levels (314.2 +/- 232.4 vs. 2076.8 +/- 1300.8 U/ml,
      1.7 +/- 0.82 vs. 4.1 +/- 2.9 ulU/ml, respectively). Thyroid dysfunction was
      detected in 7 (4.6%) children with newly diagnosed type 1 diabetes. In comparison
      to the entire group with positive serum TPO Ab titer in these 7 children the
      percentage of patients with thyroid dysfunction was significantly higher (15.5%).
      Six patients were hypothyroid and 1 had hyperthyreosis. The present results
      justify the need for comprehensive screening for thyroid disorders in all
      children with newly diagnosed type 1 diabetes.

PMID- 12516240
TI  - [Myocardial and coronary vessel dysfunction in diabetes I patients].
AB  - Despite of dramatic improvement in diagnostic procedures and treatment of
      diabetic patients, cardio-vascular complications are still the most frequent
      causes of death in these patients. Diabetes influences myocardial and coronary
      vessels function by coexisting macroangiopathy, microangiopathy, metabolic
      disturbances and autonomic nervous system neuropathy. All these factors result in
      diastolic and systolic dysfunction of the heart. Cardiomyopathy, congestive heart
      failure and serious arrhythmias are the end stage of diabetic complications.
      Macroangiopathy demonstrates accelerated atherosclerosis (involving coronary
      arteries), which consequences can be observed in 1 type diabetes patients at
      around the age of 30. Causes of increased risk of macroangiopathy in type 1
      diabetic patients are not clear. There are not many clinical, prospective trials
      which can allow for etiology determination of the increased incidence of
      atherosclerosis and mortality due to coronary artery disease in this population.
      Adding to traditional risk factors of atherosclerosis like genetic factors,
      hypertension, dyslipidemia, obesity, smoking and improper diet, other important
      risk factors are observed in diabetic patients. Only few clinical trials suggest
      that hyperglycemia, glycation, glycoxidation of proteins, lipoproteins, changes
      in their composition, microalbuminuria, coagulation, fibrinolytic disturbances
      are additional risk factors of endothelium dysfunction and atherosclerosis.
      Prevention and treatment of accelerated coronary artery disease and it's
      consequences are more complicated in the diabetic population than in others. Some
      of the clinical trials suggest that even improved glycemic control does not
      eliminate the elevated risk of coronary artery disease in type 1 diabetic
      patients.

PMID- 12516241
TI  - [Mechanisms of statin nephroprotective actions].
AB  - The great importance of HMGCoA reductase inhibitors (statins) in treatment of
      hyperlipidemia is well known, and accepted. Numerous multicenter trials have
      shown the effectiveness of statins in lowering cholesterol concentration, slowing
      down progression of atherosclerosis, and in decreasing number of cardio-vascular
      incidents. However, since the discovery of statins experiments have been carried
      out showing other mechanisms of action of these drugs. Many circumstances expose
      the antiproliferative, and antiinflammatory influence of HMGCoA reductase
      inhibitors. This paper presents a review of the studies on these mechanisms with
      a special emphasis on their nephroprotective role.

PMID- 12516242
TI  - [Sudden cardiac death and inherited repolarization disorders].
AB  - Repolarization disorders leading to ventricular tachyarrhythmias are common
      causes of sudden cardiac death. Two of the disorders have been recently described
      at the molecular level revealing gene mutations: long QT syndrome, characterized
      by a prolonged QT interval corrected for heart rate and high incidence of
      malignant ventricular tachycardia, mainly torsade de pointes, and Brugada
      syndrome characterized by a ST segment elevation in the right precordial leads
      (V1-V3), right bundle branch block and idiopathic ventricular fibrillation. This
      review outlines current understanding of molecular genetic basis and
      pathophysiology of these diseases. On the basis of these repolarization disorders
      lay ion channel dysfunctions. The new discoveries may in the future allow a
      better diagnosis by genetic testing and raise the possibility of effective
      treatment by means of the gene-specific therapy.

PMID- 12516243
TI  - [Contrast echocardiography in the assessment of left ventricular function and
      myocardial perfusion].
AB  - Myocardial contrast echocardiography is a non-invasive method used to detect
      coronary artery disease. It was first described in 1968. New contrast agents
      which can go through the pulmonary vessels were discovered in the last years.
      Contrast echocardiography is useful in improving the endocardial border
      delineation and left ventricular cavity visualisation especially in patients with
      suboptimal acoustic windows. As the contrast passes further into the coronary
      artery normal myocardium perfusion is enhanced while ischaemic areas lack
      enhancement. Analysis of perfusion allows indirect identification of narrowed
      coronary arteries. Left ventricular function and its myocardium perfusion are
      made with contrast echocardiography at rest and during pharmacological stress
      tests. These examinations allow for detection patient with coronary artery
      disease as well as estimating efficacy of revascularisation procedures.

PMID- 12516244
TI  - [Right ventricular infarction: pathophysiology, diagnosis and treatment].
AB  - Acute right ventricular ischemia accompanies 40-80% of cases of infero-posterior
      myocardial infarction. Approximately one half of these patients present with
      hemodynamic compromise consisting of acute right ventricular failure, clear lungs
      and low cardiac output in spite of preserved left ventricular systolic function.
      The ischemic right ventricle appears to be relatively resistant to infarction and
      has remarkable ability to recover. Right ventricular performance improves
      spontaneously even in the absence of reperfusion, however reperfusion enhances
      this recovery and improves the clinical course of right ventricular infarction.

PMID- 12516245
TI  - [Atrio-ventricular nodal reentrant tachycardia--concepts evolution on the
      propagation of the reentrant wave front].
AB  - Atrio-ventricular nodal reentrant tachycardia (AVNRT) is the most common narrow
      QRS tachycardia. The arrhythmia affects usually patients without any other
      structural heart disease. AVNRT may be the cause of the broad spectrum of
      symptoms, ranging from palpitations to clinical signs of impaired coronary and
      cerebral perfusion. Mechanism responsible for AVNRT is reentry, which involves
      right and some part of the left atrium. Employed in the early 80's the technique
      of radiofrequency current (RF) ablation (which allows removal of arrhythmic
      substrate by modification or destruction of the slow pathway), is safe and a high
      effective method of treatment in patients with AVNRT.

PMID- 12516246
TI  - [Clinical types of acanthosis nigricans].
AB  - Acanthosis nigricans is a rare disease, occurring with the same frequency in
      females and males. Eight clinically practical types of this disease have been
      presented. Authors also observed a coexistence of this disease with neoplasms,
      which obligates doctors to perform more accurate diagnosis of the patient. The
      clinically practical scale of the intensification of skin lesions in acanthosis
      nigricans has been also presented. This scale is helpful in therapy monitoring.

PMID- 12516247
TI  - [Acromegaly--do we already know everything about treatment of the somatotroph
      pituitary adenomas?].
AB  - Acromegaly--do we already know everything about treatment of the somatotroph
      pituitary adenomas?--Acromegaly, an insidious neuroendocrine disorder, reduces
      life expectancy and leads to 3.5-fold increase in mortality. The main causes are
      cardiovascular, pulmonary and enhanced prevalence of deaths from malignancy.
      Successful therapy ought to normalize GH, IGF-I secretion, remove adenoma mass
      and its local pressure effects and preserve pituitary function to improve
      systemic morbidity and normalize mortality. The primary therapy for most patients
      with acromegaly caused by somatotroph pituitary adenoma is still transsphenoidal
      resection of the tumor. The results of the transsphenoidal surgery for pituitary
      adenoma for acromegaly depend on the volume of the tumor, its suprasellar and
      parasellar extension, especially to the cavernous sinus. The aim of this paper
      was to present the diagnostic criteria and principle therapy in these tumors. Our
      experience was based on the analysis of more than 150 patients operated on during
      the last five years and review of the literature.

PMID- 12516248
TI  - [Calcifications of basal ganglia and cerebellum in patient with
      pseudohypoparathyroidism--case report].
AB  - Presented is the case report of symmetrical calcifications of basal ganglia,
      cerebellum and subcortical white matter of cerebral hemispheres (Fahr's syndrome)
      in a 34 year old man with pseudohypoparathyroidism. Attention has been put on
      characteristic features of Fahr's syndrome and differential diagnosis of this
      rare disease.

PMID- 12516249
TI  - [The first case of metastatic tumor of the right orbit in Otolaryngology
      Department of the Jagiellonian University in Krakow].
AB  - We report the case of a 30-year old woman, who was admitted to our hospital
      because of tumor of the right orbit. It is the first case of metastatic tumor in
      this localization in the Otolaryngologist Department of the Jagiellonian
      University in Krakow. It appeared, that mammary cancer was the primary
      localization of the lesion. We present characteristic features of that tumor and
      we compare them with features of the metastasis to the left orbit in patients who
      were treated in our Department. Breast carcinoma is the most common reason of
      metastasis to orbit in women. Metastatic tumors in the right orbit are rare, but
      they can appear.

PMID- 12516250
TI  - [Management of coexistent advanced coronary artery disease and internal carotid
      artery stenosis].
AB  - We discuss a case of a 60-year old man admitted to our Department with symptoms
      of unstable angina and stenosis of carotid artery. Coronary angiography revealed
      three-vessel coronary artery disease. Doppler ultrasound (USG) and multislice
      spiral computed tomography (MSCT) of carotid and vertebral arteries showed a high
      grade stenosis of the left internal carotid artery with a poststenotic aneurysm
      containing thrombi. Since the risk of a simultaneous coronary artery bypass
      grafting (CABG) and carotid endarterectomy (CEA) was assessed as high, a two
      staged procedure was performed. The CEA was performed first and one month later
      patient underwent CABG with a good result.

PMID- 12516251
TI  - [Sectio ceasarea isthmicolongitudinalis--a forgotten beginning and/or groundless
      fear?].
AB  - A retrospective analysis of the frequency, indications, intra- and postoperative
      complications in isthmicotansverse (ITS) and isthmicolongitudinal (ILS) cesarean
      section has been conducted with a view to justifying the wider application of ISL
      in modern obstetrics. For a five-year period (1996-2000) at the Obstetrics and
      Gynecology Clinic of St. Ann Hospital-Sofia a total of 522 cesarean section were
      performed of which 348 (66.7%) with isthmicotansverse incision and 174 (33.3%)
      with isthmicolongitudinal incision. The data show that ILS were ith less blood
      loss and with less intra- and postoperative complications and it was applied in
      all types of obstetric indications and urgent cases. Having in mind the good
      results and the fact that ILS is a technique which could be performed by every
      obstetrician familiar with ITS, The authors are convinced that
      isthmicolongitudinal cesarean section can find a wider application in everyday
      obstetric practice.

PMID- 12516252
TI  - [The impact of some factors on obstetrical management in women with previous
      cesarean section].
AB  - Considering obstetrical management we should have always in mind advantages and
      disadvantages of vaginal birth after cesarean (VBAC) and elective cesarean
      section after a previous one, financial part of the elected mode of delivery in
      the particular case, psychological aspect of the matter (especially after an
      unsuccessful trial of labour--TOL) and not on the last position-patient's right
      to choose the way how to deliver. We performed an inquiry of 3-year-period and 50
      women with a prior cesarean section, by which we studied the factors contributed
      in different extent to the choice of the following approach to delivery:
      patient's preliminary choice, the impact of medical staff during pregnancy and
      when entering the Department of Obstetrics, the impact of non-medical persons,
      complications after the previous cesarean section, patient's acquaintance with
      complications and consequences associated with the operative mode of delivery, as
      well as doctor's personal attitude to the different modes of delivery. The aim of
      our research is to show that by careful selection (according to the established
      indices) of women, who have a high probability (more than 80%) to deliver their
      babies vaginally and offering adequate information by educational literature and
      including the woman in the decision making process, the growing rate of cesarean
      section will be decreased by increasing the number of VBAC--undoubtedly one of
      the most important issue in modern obstetrics.

PMID- 12516253
TI  - [Utrogestan--an alternative for synthetic gestagen treatment in spontaneous
      abortion].
AB  - A clinical trial is conducted with 32 pregnant patients with a history of
      sterility and infertility, uterine malformations as well as progesterone
      deficiency. The mean week of gestation is 9-10. All patients were treated with
      Utrogestan in the usual doses 2 x 100 mg for vaginal application. No side effects
      were observed which is encouraging to its routine use.

PMID- 12516254
TI  - [Treatment with human chorion-gonadotropin (pregnyl) of patients with vaginal
      bleeding in the first trimester of pregnancy].
AB  - The author present a few years opinion for treatment of patients with vaginal
      bleeding in first trimester of pregnancy and obstetrical complications with
      Pregnyl(Organon). The basics factors for inclusion in examination group are
      pregnant women in early pregnancy complicated with vaginal bleeding, with or not
      a pain. Overall 34 patients whose be treatment, 31 delivered lived and health
      child, one patient delivered baby with osteogenesis imperfecta and 2 patients the
      pregnancy is bracked with spontaneous abortion. The treatment with Pregnyl is
      very good method in patients with infertilitas, polycystosis ovarii and vaginal
      bleeding in early pregnancy. The doses of Pregnyl is 10,000 E i.m. (bolus dose),
      5,000 E i.m. two times weekly between the first dose and 10 weeks of pregnancy,
      5,000 E i.m. weekly between 10 and 14 weeks of pregnancy.

PMID- 12516255
TI  - [Diagnostic value of the ultrasound screening for osteoporosis in postmenopausal
      women].
AB  - Quantitative ultrasound (QUS) of the calcaneus quickly introduced itself as a
      useful diagnostic tool in osteoporosis. The purpose of this study was to assess
      its diagnostic value in postmenopausal women as compared to DXA of vertebral
      bodies. 100 postmenopausal women (mean age 48 years) were included and underwent
      calcaneal QUS (Lunar Achilles+ device) and dual-energy X-ray absorptiometry of
      the vertebral bodies (Hologic QDR 4500 A unit). Mean QUS T-score was -2.38, and
      mean DXA T-score was -2.06 standard deviations. Both measurements classified
      equal proportions of women as normal (4 versus 12%), osteopenic (55% in both
      cases), and osteoporotic (41 versus 33%). In detecting osteoporosis QUS showed
      58% sensitivity and 47% specificity. When assessing fracture risk (osteoporosis
      and osteopenia) QUS showed 100% sensitivity and 92% specificity. The negative
      predictive value of QUS always exceeded the positive one. QUS is a valuable tool
      in primary screening for increased fracture risk. Alerting results require
      further examinations.

PMID- 12516256
TI  - [Our first experience with the flexible office hysteroscopy].
AB  - Authors analyzed 200 women with the help of flexible office hysteroscopy without
      anaesthesia and cervical dilatation in ambulatoric conditions. Basic purpose of
      this scientific checkout is to estimate diagnostic value of the method and also
      the ability of application in out of hospital net. 194 cases of all ware
      successfully having in mind that all investigations were carries out without
      previous premedication and anaesthesia. As a result of this first attempt using
      this method authors can conclude that flexible office hysteroscopy is highly
      sensitive, specific, harmless and tolerable method.

PMID- 12516257
TI  - [Hysteroscopic findings in women with abnormal uterine bleeding according to the
      materials from the department of obstetrics and gynecology, medical university-
      Plovdiv].
AB  - The results of a four-year period are analyzed. For this time 479 diagnostic
      panoramic hysteroscopies were performed. By 152 patients (31.7%) the main
      complaint was abnormal uterine bleeding. All hysteroscopies were followed by
      histological examination. The specimens have been taken by target biopsy and
      curretage. The age of the patients ranged from 40 to 75 years. Pointed is a
      frequency of this pathology and its distribution by age. The authors show the
      priority of the diagnostic panoramic hysteroscopy in consideration with the other
      methods of investigation--D & C and sonography, in fact-exactly diagnosis and
      avoiding unnecessary curretage.

PMID- 12516258
TI  - [Evaluation of the relationship between the endometrial thickness and the
      administration of hormone replacement therapy in postmenopausal women].
AB  - In our investigation we wanted to evaluate the effect of HRT on the endometrial
      thickness and artery blood flow. For 10 years period from 1992 till 2002 we
      evaluated 275 patients in postmenopause. All were examined by vaginal
      ultrasonography. We divided the patients into 3 groups--the first group--85
      patients receiving HRT (hormonal replacement therapy), the second group--146
      asymptomatic women in postmenopause and the third group--40 women with
      pathological bleeding in postmenopause. There was no difference in the
      endometrial thickness between the patients receiving HRT and the other two groups
      of women. The endometrial pathology influenced the endometrial thickness as well
      as the uterine blood flow.

PMID- 12516259
TI  - [Lipid metabolism and its changes in pregnancy].
AB  - A survey is made on physiology of lipid metabolism and its variations during
      pregnancy. The mechanisms leading to an increase in triglycerides and cholesterol
      during pregnancy are explained. These changes induce increased aterogenic risk,
      higher risk for developing pathologic 1 changes in blood vessels on
      microcirculation level on the basis of endothelial disfunction. A multiorgan
      pathology may possibly be provoked--kidneys, pancreas or occurrence of
      praeeclampsia.

PMID- 12516260
TI  - [The microorganisms associated with bacterial vaginosis as a cause of tubal
      sterility].
AB  - Bacterial vaginosis is one of the most widespread disturbances of the normal
      state of the vagina of women of reproductive and menopausal age. This condition
      is highly disregarded due to its moderate and not always clear clinical
      manifestation. The disturbed proportion of microorganisms in vagina is shown in
      the strong decrease or lack of lactobacilli and a spread of associated with
      bacterial vaginosis microorganisms. G. vaginalis, Mobiluncis spp., Bacteroides
      spp. (without B. fragilis), Peptostreptococcus spp., Mycoplasma hominis,
      Ureaplasma urealyticum. The condition is a predisposition to a disturbance of
      natural defense mechanisms and to a spread of infectious agents towards the upper
      female genital tract. This is a predisposition for the development of tubal
      patency and motility disorders, ovarian function disturbances, endometrites. The
      treatment of this condition as an important step in female sterility prophylaxis
      is commented.

PMID- 12516261
TI  - [Neoadjuvant chemotherapy in locally advanced squamous carcinoma of the uterine
      cervix (IB2 - IIIB stage)].

PMID- 12516262
TI  - [A case of unruptured intrafollicular ovarian pregnancy diagnosed prior to
      operation].
AB  - A case of an unruptured intrafollicular ovarian pregnancy of 8 gestational weeks
      diagnosed by ultrasonography in a virtually asymptomatic patient is reported. A
      32 year-old woman with 1 vaginal delivery 8 years ago presented with a history of
      intermittent spotting after removal of an IUD during her last menstrual period 4
      weeks ago. IUD was inserted 6 years prior. The patient was symptom-free and
      showed no abnormal findings upon vaginal examination. Transvaginal
      ultrasonography however disclosed a gestational sac with a live embryo within the
      left ovary. The woman was operated on via laparotomy without delay. The
      intraoperative finding showed a normally appearing corpus luteum in the intact
      left ovary without any visible abnormality of the pelvic organs. Having in mind
      the US finding a resection of the corpus luteum was done revealing the
      gestational sac within it. The authors describe the following three US signs
      specific of unruptured intrafollicular ovarian pregnancy: extremely thickened
      uniformly echogenic wall of the sac, the sac is partially surrounded by ovarian
      structure, no corpus luteum is detected in either ovary. The essential role of
      transvaginal ultrasonography in the precise diagnosis of the ectopic pregnancy
      and its location is emphasized. The absence of specific complaints and findings
      until rupture of the ovary occurs and the association of ovarian pregnancy and
      IUD are also confirmed by the case-report.

PMID- 12516263
TI  - [Mullerian papilloma in the vagina of a two year old girl--a case report].

PMID- 12516264
TI  - [Vulvar reconstruction with myocutaneous flaps from musculus tensor fasciae latae
      after block-resection for vulvar cancer].
AB  - Up-to date treatment of oncological diseases, in particular the vulvar cancer,
      leads to increasing of survival, in which to the foreground outlines not only the
      physical health but as well better social adaptation, sexual and adequate mental
      life of patients. Reconstructive surgery takes place in the oncological practice
      more and more. For vulvar reconstruction after operative treatment can be used
      cutaneous flaps and grafts, skin-fascial and myocutaneous flaps. The autors
      present their experience by describing in details the technique of vulvar
      reconstruction by myocutaneous flaps from m. tensor fasciae latae. It helps for
      eliminating the negative results of enlarged operative therapy.

PMID- 12516265
TI  - [Determination of the time of death according to rectal thermometry data using
      computer calculations].
AB  - A mathematic model of estimation of time of death (TD) in newborns is proposed.
      This computer method of TD timing by changes of body temperature differs from
      earlier developed mathematical models by possibility to consider individual
      anthropometric and thermophysical characteristics of the body. It is more
      precise, shorter and easy to perform.

PMID- 12516266
TI  - [Infrared spectroscopy of the dry residue of liquor crystallograms in various
      diseases].
AB  - The article presents the results of an examination of the dry residue of liquor
      crystallograms (DRLC) using infrared spectroscopy technique. 36 spectrograms were
      studied. Elements of similarity and difference were revealed in the spectrograms
      of organic substance (antifreeze, sodium cyclamate and fatty tissue), of DRLC of
      the crystal-forming matter CuCl(2)x2H(2)0, of DRLC of a live person and cadaveric
      liquor (with no brain injury in respective case histories), of DRLC of liquor of
      live persons with a brain injury, of DRLC of liquor of persons who died of a
      brain injury and of persons who died of other causes.

PMID- 12516267
TI  - [Craniometric diagnosis of skeletal and somatotype mass].
AB  - The paper presents diagnostic models for evaluation of ash mass (bone fragments,
      bone ashes), sex, length and mass of the burned body. Individual data by M.
      Warren and W. Maples (1997) on 85 adult Americans were used. On the basis of a
      canonical discriminant analysis and multiple linear regression equations the
      authors have developed models for diagnosis of ash residue mass as well as the
      burned body's sex, body length and mass. The above models can be used directly on
      the place of the criminal body cremation. They do not require determination of
      anatomic appurtenance of bone fragments and their osteometric examination.

PMID- 12516268
TI  - [Allele polymorphism of molecular-genetic individualizing systems based on
      tetranucleotide tandem repeats LPL, vWA and TH01 among the population of Russia].
AB  - Until recently, data bases on incidence rates of alleles STR (LPL, vWA and THO1
      loci) have not been introduced in Russia. To obtain information on the above
      rates in Russia, a large scale research of distribution of LPL, vWA and Tho1 loci
      has been performed among a sample of 442 blood-unrelated persons from 57 regions
      of the Russian Federation to specify basic assessment characteristics of these
      loci and to raise efficiency of expert use of identifying systems on their base.
      Relevant parameters (allele frequencies) are presented for each polymorphic locus
      as well as basic population characteristics of polymorphism in the studied sample
      of RF population. These results can be used as key parameters for standard
      probability estimations in assessing the results of molecular-genetic
      identification.

PMID- 12516269
TI  - [Design of the automatic system of processing data on mitochondrial DNA
      "mDNAbase" sequestration for expert identification of the unidentified bodies
      under the conditions of mass reception of human remains].
AB  - The authors consider utilization of software which provides indirect personality
      identification by establishment of biological kinship using a comparative
      analysis of nucleotide sequences (NS) of mitochondrial DNA (mtDNA) in
      unidentified bodies and suspected relatives of these victims. The software
      supports data bases with information on NS. To secure automatic search there are
      modes of cross-processing. Results of identification are formed as lists of
      exclusions and tables with calculated frequencies of mitotypes of identification
      objects as well as protocols of a comparative analysis of nucleotide position in
      mtDNA sequences under comparison. The proposed computer approach is a new highly
      effective tool for identification of personality based on data on mtDNA analysis
      in conditions of stream information processing under mass reception of
      unidentified bodies.

PMID- 12516270
TI  - [Effects of biological factors on isoantigens of ABO system].
AB  - The paper provides data about alterations of antigen ABO system in pathological
      states. These changes result from emergence and following action of the enzyme
      neuromidase to form latent determinant T.

PMID- 12516271
TI  - [Detection of ABO and GM system antigens in the teeth].
AB  - A series of experiments using agglutination inhibition reaction and material
      extraction in PBS with pH 7.2 (phosphate-buffer-sedin) has been made to detect
      antigens of the GM system in the teeth. Parameters of the test material/serum
      ratio are proposed. In parallel, control specimens of blood were examined. The
      results of the experiments suggest that detection of Gm antigens in the teeth is
      feasible. In some cases this may raise an identification level of the expert
      conclusions. The above technique can be used for investigation of the bones.

PMID- 12516272
TI  - [Analysis of the frequency of various blood groups among the population of the
      Udmurt republic from 1994-2001].
AB  - Statistics are presented on the incidence of blood groups of 6 systems in the
      population of the Udmurt Republic. The data are compared with the results of
      similar surveys in other regions of the Russian Federation.

PMID- 12516273
TI  - [Morphological characteristics of head hairs and hairs from other parts of the
      body in the population of Asia].
AB  - The paper describes specific morphological features of hairs from the head,
      beard, chest, axilla, pubis of the native population of Syria, India, Lebanon,
      Jordan, Yemen, Nepal, Palestine, Bahrain, Iraq and some residents of the Eastern
      Europe (Russians, Belorussians, Ukrainians). The hairs were studied
      macroscopically and microscopically (light microscopy). Digital data on hair
      thickness and number of lines of cuticula pattern were analysed using methods of
      variance statistics. Original information on some macro- and microscopic
      characteristics of hair has been obtained for citizens of the above countries.

PMID- 12516274
TI  - [Morphological structure of the domestic cat (Felis catus) hair].
AB  - Felis catus hairs from different parts of its body were examined. Examination of
      some hair parameters allow the author to propose the following strategy of cat
      identification: 1) hair length divides cats into long- and short-haired; 2)
      identification of the species: a) long-haired--by medullary substance/hair
      thickness ratio; b) short-haired--by the presence or absence of osteal and
      transition hairs, by thickness of the osteal hairs. This scheme allows
      identification of the species of an individual cat.

PMID- 12516275
TI  - [Forensic medical evaluation of the morphological alterations of the liver in
      drug abuse].
AB  - Application of a morphometric method for investigation of chronic virus hepatitis
      in drug addicts and persons rejecting drug abuse is described. Chronic hepatitis
      in narcomania runs with frequent formation of lymphoid follicules in the portal
      tracts, relatively inactive portal hepatitis in marked lobular component of
      inflammation, pronounced fibrosis and early formation of micronodular hepatic
      cirrhosis, proliferation of biliary ducts, high neutrophil, eosinophil and
      macrophage content in the infiltrate, accumulation of macrophages in the portal
      tracts by granuloma type. These criteria are recommended for diagnosis of
      narcomania by morphological findings.

PMID- 12516276
TI  - [The use of scanners in forensic medicine].
AB  - The paper describes usage of scanners with computer image processing for
      illustrations and as an independent method of clues examination in forensic
      medical practice.

PMID- 12516277
TI  - [Purification of extracts from biological material using aluminum oxide].
AB  - An effective, rapid, and safe operation is suggested for purification of extracts
      from biological material from co-extractive substances during testing for
      barbiturates, benzophenones, and nichlofolane. The purification is carried out on
      a column packed with aluminum oxide.

PMID- 12516278
TI  - [Sepsis in a 4-year-old child with immunodeficiency].

PMID- 12516279
TI  - [Kell system: current ideas about structure, function, antigen nomenclature,
      methods of detection, and forensic-medical significance].

PMID- 12516280
TI  - [Forensic-medical expert examination in sex crimes].

PMID- 12516281
TI  - [Hepatitis B immunization and persistence of immunologic memory].

PMID- 12516282
TI  - [Recurrence of focal glomerulosclerosis after renal transplantation].

PMID- 12516283
TI  - [Quality improvement systems in nephrology units].

PMID- 12516284
TI  - [Electronic medical records in a recently created nephrology service].

PMID- 12516285
TI  - [2002 consensus document about the detection, prevention and treatment of
      diabetic nephropathy in Spain].

PMID- 12516286
TI  - [Type II essential mixed cryoglobulinemia and renal disease. Hepatitis C virus
      association].
AB  - Recently a number of studies have implicated C virus as a major cause of mixed
      cryoglobulinemia. Several authors described that up to 95% of "essential" mixed
      cryoglobulinemia could be attributed to this viral infection. Nevertheless, its
      prevalence and clinical significance are not well known. We review our experience
      in relation with the clinical, biological and evolutive characteristics of
      patients diagnosed of type II mixed cryoglobulinemia. METHODS: Descriptive and
      protocolized study of all cases found to have type II mixed cryoglobulinemia over
      a period of 8 years. Secondary cryoglobulinemic nephropathy was defined in a
      restrictive way: a plasma creatinine > 1.5 mg/dl and/or proteinuria > 500 mg/24 h
      and/or hematuria (> 15 red blood cells) need to be present in the absence of any
      other pathological conditions that could justify these alterations. Furthermore,
      the information obtained from available kidney biopsies was considered. RESULTS:
      62 patients have been detected. C virus infection was demonstrated in 44 (72%).
      52% had clinical symptoms related with cryoglobulinemia. 56% had alteration of
      renal tests, and 17 (27%) fulfil the conditions for the diagnosis of
      cryoglobulinemic nephropathy (nearly all with persistent microhematuria, median
      proteinuria 4.2 +/- 3.9 g/24 h; median plasma creatinine 2.8 +/- 1.8 mg/dl). Nine
      patients had been histologically examined, showing 6 cases a
      membranoproliferative glomerulonephritis pattern, one with associated
      extraglomerular vasculitis; two with mesangial proliferative pattern and one with
      membranous glomerulonephritis. The most striking differences between
      cryoglobulinemic nephropathy patients and the rest has been: higher amount of
      cryoglobulins (49 +/- 28 vs 20 +/- 22); more frequent hypocomplementemia,
      especially C4 (93% vs 59%) and recurrent purpura (75% vs 32%). No differences in
      the presence of C virus infection could be observed (75% vs 71%). IN CONCLUSION:
      72% of patients with type II mixed cryoglobulinemia are infected by C virus (so
      28% in our serie are "essential"); 52% have symptoms related with the presence of
      cryoglobulins, half of them with cryoglobulinemic nephropathy.

PMID- 12516287
TI  - [Fabry disease: clinic and enzymatic diagnosis of homozygous and heterozygous.
      New therapeutic prospects].
AB  - Fabry disease is an X-linked recessive lysosomal storage disorder caused by a
      partial or complete deficiency of alpha-galactosidase A. Intracellular
      accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme,
      leads to severe painful neuropathy with progressive renal, cardiovascular, and
      cerebrovascular dysfunction and early death. Men are predominantly affected but
      many female carriers have similar clinical involvement, including increased risk
      of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes
      and characteristic benign corneal abnormalities, facilitate identification of
      Fabry disease. The finding of a marked decreased activity of (alpha-galactosidase
      A in plasma, white blood cells or cultured skin fibroblasts confirms the
      diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies
      are being developed that include enzyme replacement therapy, gene therapy, and
      substrate deprivation. The recently completed double-blind, placebo-controlled
      trials of intravenous infusions of (alpha-galactosidase A in patients with Fabry
      disease demonstrated the safety and efficacy of this treatment. We report a
      family with Fabry disease composed of hemicygous and heterocygous. The propositus
      developed chronic renal failure and received a cadaver renal transplant, which
      remained with adequate renal function during 15 years.

PMID- 12516288
TI  - [Characteristics of acute renal failure in elderly patients admitted to a small
      town hospital].
AB  - We studied the features of acute renal failure (ARF) in elderly patients treated
      in a hospital, without an intensive care unit, to identify etiological factors
      and establish adequate preventive measures and treatment. During twelve
      consecutive months we studied prospectively 99 patients with ARF diagnosed by
      conventional criteria, an incidence of 1,238 cases per million per year. ARF
      affected 1.78% of patients admitted to hospital. We analyzed age, sex, serum
      creatinine, diuresis, etiology, type of ARF, preexisting chronic diseases,
      treatment, complications and outcome. Preexisting chronic diseases were common,
      the most frequent being hypertension (54%) and diabetes (39%). Previous
      treatments for cardiovascular diseases were frequent (angiotensin-renin system
      blockade 35.4%, diuretics 50.5%). 79% of ARF arose in hospital, 21% outside
      hospital. ARF was pre-renal in 60%, renal in 31% and post-renal in 9%. 34.7% were
      caused by volume depletion, 23.4% by low cardiac output and 23.4% by infection.
      44.4% of ARF patients had oliguria or anuria latrogenic factors contributed to
      the ethiology of ARF in 35.3% of patients. Hospital stay was doubled by ARF the
      presence of ARF and the mortality was 36.4%. The rate was higher in ARF arising
      in hospital than in ARF acquired before admission. Factors that had a significant
      influence on the mortality rate were comorbid conditions, oliguroanuria, ARF of
      renal origin and serum albumin. We conclude that ARF has a high incidence,
      morbidity and mortality in this elderly population. Volume depletion, associated
      cardiovascular pathology and pharmacological treatment are important etiological
      factors in those with ARF outside hospital. Adequate treatment of ARF and
      avoidance of nephrotoxic medications are necessary in hospital.

PMID- 12516289
TI  - [Anemia management in haemodialysis. EuCliD database in Spain].
AB  - We present the results on Anaemia Management in Fresenius Medical Care Spain
      dialysis centres as reported by EuCliD (European Clinical Database), evaluating a
      population of 4,426 patients treated in Spain during the year 2001. To analyse
      the erythropoietin dose and the haemoglobin levels we divided the population in
      two groups according to the time with dialysis treatment: patients treated less
      than six months and patients between six months, and four years on therapy. We
      compared our results with the evidence based recommendations Guidelines: the
      European Best Practice Guidelines (EBPG) and the US National Kidney Foundation
      (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on
      2,618 patients on dialysis in Spain carried out in the second half of the year
      2000. We observed that 70% of the population reaches an haemoglobin value higher
      that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg
      weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for
      less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD
      1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients.
      About the iron therapy, 86% of the patients received iron treatment and the
      administration route was intravenous in 93% of the population. The ferritin
      levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a
      transferrin saturation index (TSAT) below 20%. The erythropoieting resistance
      index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to
      rHu-Epo, according to different variables. It was observed that the following
      factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as
      administration route, the presence of hypoalbuminemia, increase of protein C
      reactive, Transferrin saturation below 20% and starting dialysis during the last
      six months.

PMID- 12516290
TI  - [Partial lipodystrophy in two HLA identical sisters with hypocomplementemia and
      nephropathy].
AB  - Partial lipodystrophy is a rare disorder with both autosomal recessive and
      familial forms. The cutaneous findings, which are often subtle, consist of
      gradual loss of subcutaneous fat from the face and upper body. Low levels of C3
      and the presence of C3NeF help to identify these patients. Associated systemic
      abnormalities include the development of membranoproliferative
      glomerulonephritis, insulin resistance and an increased incidence of autoimmune
      diseases. We report here two HLA identical sisters with the typical features of
      partial lipodystrophy associated with recurrent infections, low levels of C3, and
      nephropathy. Our data suggest an autosomal recessive transmission. We discuss the
      genetic and molecular basis of this rare association.

PMID- 12516291
TI  - [Porphyria cutanea tarda, hemodialysis and HCV hepatopathy].
AB  - Porphyria cutanea tarda is treated with phlebotomies in the absence of renal
      failure. However, in patients on maintenance hemodialysis, this will lead to the
      need for high doses of erythropoietin. We describe the case of a 63-year-old
      hemodialysis patient who had chronic hepatitis C virus and developed porphyria
      cutanea tarda after iron overload due to repeated transfusions. She was treated
      with erythropoietin and phlebotomies reaching clinical remission 4 months after
      beginning treatment.

PMID- 12516292
TI  - [Remission of severe disease induced by CMV and lymphoproliferative post
      transplant disease after changing the immunosuppressive regime].
AB  - We describe a renal transplant recipient, with overimmunosuppression induced by
      the interaction of tacrolimus and fluconazole, who developed two severe diseases
      produced by two different viruses of the herpes group (cytomegalovirus [CMV]
      disease and posttransplant lymphoproliferative [PTLD] disease EBV-related).
      Detection of Epstein-Barr virus (EBV) DNA in the blood preceded the histological
      diagnosis of PTLD. Both diseases improved after changes in the immunosuppressive
      regime and treatment with ganciclovir. Because CMV infection is a risk factor in
      developing PTLD, and the clinical and endoscopic manifestations of both diseases
      could be become confused, PTLD should be excluded in EBV seronegative patients
      that develop CMV disease. The detection of the EBV genome in blood could help in
      the early diagnosis of PTLD in these patients.

PMID- 12516293
TI  - [Membranoproliferative glomerulonephritis associated to Hepatitis C virus
      infection].

PMID- 12516294
TI  - [Membranous nephropathy with ankylosing spondylitis ].

PMID- 12516295
TI  - [Usefulness of CA-125 as marker of extrapulmonary tuberculosis in hemodialysis
      patients].

PMID- 12516296
TI  - [Malignant Hypertension?].

PMID- 12516297
TI  - [Structure and activity of the Research Institute for Forensic Medicine].

PMID- 12516298
TI  - [Organisation of interaction of the forensic medical service with law
      enforcement].

PMID- 12516299
TI  - [The forensic description of torn cerebral aneurysms].
AB  - 103 studies of torn aneurysms in the cerebral vessels are described.
      Localizations, morphological peculiarities of aneurysms as well as the nature of
      intracranial hemorrhages caused by torn aneurysms are presented. The authors have
      a critical attitude to the "acquired" theory of aneurysm development.

PMID- 12516300
TI  - [Examination of ash mass for identification of remains].
AB  - Diagnostic models designed for examining the ash mass (fragments of bones and
      osteal ash) as well as of sex, height and weight of burnt human being are
      described.

PMID- 12516301
TI  - [Characteristics of blood circulation in the lungs during the early period after
      blunt multiple trauma].
AB  - The microscopic and histostereometric examinations of specific features of blood
      circulation in the lungs (in lethal cases) performed during the early period
      after combined trauma showed pronounced disturbances of blood circulation in body
      organs which had a certain sequence in the development of vascular reactions and
      vascular temporal dynamics. The influence of a preceding alcoholic intoxication
      and intensive hemorrhage on the circulatory dynamics was demonstrated.

PMID- 12516302
TI  - [The role of cytomedins in establishing the sequence of causing injuries].
AB  - The results of investigation of biological activity of information molecules,
      i.e. cytomedines, obtained from injuries by using the method of acetous
      extraction (V.G. Morozov, V. Kh. Havinson, 1981) are presented in the
      experimental manner and on the basis of practical materials. The sequence of
      formation of hemorrhages and injuries was demonstrated accurately enough by using
      the biological activity of extracted cytomedines.

PMID- 12516303
TI  - [The experience of using the FTA-carriers for blood sample storage while
      conducting the molecular-genetic identification of unidentified killed persons-
      victims of military actions in the territory of the Chechen Republic].
AB  - The activity of adapting and introducing the FTA-carriers for the storage of
      blood samples of relatives of missing service men for the purpose of using them
      in the consequent identification measures in respect to non-identified killed
      persons has been conducted in the Russian Federation within the framework of
      identification of service men killed in the Chechen territory during the 1994
      1996 armed conflict. The article generalizes the experience of practical usage of
      FTA-cards as an element in the technological sequence of the molecular-genetic
      identification expertise. Methods related with application of FTA-technologies
      were tested; the efficiency of polymerized chain reaction was evaluated by using
      the matrix of immobilized DNA for hypo variable segments HVS-1 and HVS-2 as well
      as for the D-loop of mitochondrial DNA and for chromosomal STR-locuses D3S1358,
      vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820.

PMID- 12516304
TI  - [Distribution of D1S80 alleles in a random sample of the population of the
      Russian Federation].
AB  - The distribution of alleles of chromosomal locus D1S80 was studied within a
      random selection of population of the Russian Federation. Typing was made for 255
      persons who were not blood relatives and who lived in 56 Russia's regions. A
      correlation was found between the observed frequencies of genotypes and those
      theoretically expected and estimated on the basis of the hypothesis of Hardy
      Weinberg equilibrium. The main population characteristics of locus D1S80, i.e.
      probability of an incidental coincidence of a genotype, discriminating potential,
      polymorphism factor, potential excluding cases of incorrectly named parents and
      mean value of paternity index, were estimated to evaluate the efficiency of the
      locus as a molecular-genetic marker in solving the identification tasks
      applicable to Russia's population. The obtained descriptive data on the
      distribution of alleles of the studied locus in Russia's population can be used
      to determine the needed estimated parameters in interpreting the results of
      forensic molecular-genetic identification examinations.

PMID- 12516305
TI  - [The use of capillary electrophoresis for the study of D13S317 and D7S820
      microsatellites in Caucasian population of the Ural region of Russia].
AB  - A method for the simultaneous amplification and typing of microsatellites D13S17
      and D7S820 by using monocomplex sets GenePrint Fluorescent STR Systems ("Promega
      Corp.", USA) was worked out. The offered method is accurate, reproductive,
      sensitive and needs a short time for analysis. Allele frequencies D13S17 and
      D7S820 for the above mentioned Caucasians were determined on the population
      sample of 120 persons who were not relatives and who resided in the Ural region
      of Russia. The genotype frequencies of both locuses in this population sample did
      not differ statistically from Hardy-Weinberg equilibrium. The aggregate
      discrimination factor for both locuses amounted to 0.995. The null hypothesis of
      independence among locuses D13S17 and D7S820 was checked by using an accurate
      test. No relation was found between alleles of the 2 tested locuses in the
      population sample of Ural Caucasians. The testing of the null hypothesis of the
      population homogeneity of allele frequencies of the examined locuses showed,
      among 5 Caucasian population samples, a reliable difference only for locus D7S802
      in case of a couple of an Ural and Polish population sample. Allele frequencies
      for other couples were homogeneous.

PMID- 12516306
TI  - [Forensic evaluation of the results of chemical and toxicological analysis of
      blood alcohol level].
AB  - According to printed research results, the endogenic level of ethanol in blood
      amounts to 0.001-0.3%, the physiological level amounts to 0.01-0.4% and the
      lethal level amounts to 3-17.6%. It was established experimentally that the
      absolute lethal level of ethanol in blood does not exceed 15%. Criteria of
      incidental contamination of analyzed blood sample with ethanol are described.

PMID- 12516307
TI  - [Extraction of 2-amino-4-nitrophenol and 4-phenylphenol from aqueous solutions].
AB  - The authors provide the results of extraction of 2-amino-4-nitrophenol and 4
      phenilphenol from aqueous solutions by five organic soluvants. The dependence of
      the extraction degree on some factors (nature of extragent, pH of aqueous phase
      medium, extragents saturation with water) was established. Necessary extraction
      rate for isolation of preset quality of the test substances was calculated.

PMID- 12516308
TI  - [Forensic and ballistic aspects of gunshot injury of M. I. Kutuzov in 1788].

PMID- 12516309
TI  - The role of psychoneuroimmunology in psychiatry.

PMID- 12516310
TI  - World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the
      pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic
      stress disorders.
AB  - In this report, recommendations for the pharmacological treatment of anxiety and
      obsessive-compulsive disorders are presented, based on available randomized,
      placebo- or comparator-controlled clinical studies. Selective serotonin reuptake
      inhibitors (SSRIs) are the first-line treatment for panic disorder. Tri2-cyclic
      antidepressants (TCAs) are equally effective, but they are less well tolerated
      than the SSRIs. In treatment-resistant cases, benzodiazepines like alprazolam may
      be used when the patient does not have a history of dependency and tolerance. Due
      to possible serious side effects and interactions with other drugs and food
      components, the irreversible monamine oxidase inhibitor (MAOI) phenelzine should
      be used only when first-line drugs have failed. In generalised anxiety disorder,
      venlafaxine and SSRIs can be recommended, while buspirone and imipramine may be
      alternatives. For social phobia, SSRIs are recommended for the first line, and
      MAOIs, moclobemide and benzodiazepines as second line. Obsessive-compulsive
      disorder is best treated with SSRIs or clomipramine.

PMID- 12516311
TI  - The concept of hebephrenia over the course of time with particular reference to
      the Wernicke-Kleist-Leonhard School.
AB  - The concept of hebephrenia has undergone more changes than almost any other
      diagnostic category in clinical psychiatry. In the present article we want to
      outline these changes from Hecker's first description of hebephrenia to
      contemporary concepts mainly based on Bleuler's viewpoints. Due to rather
      heterogeneous and vaguely defined symptomatology, hebephrenia lost relevance as a
      diagnostic category in today's classification systems. As an alternative
      approach, Kleist and Leonhard see hebephrenias as forming distinct clinical
      entities with insidious beginning and a chronically progressive course leading to
      specific and stable residual syndromes, mainly featured by disturbed affectivity
      and, thus, initiative. As known up to now, hebephrenias within Leonhard's
      classification show poor prognosis, little response to treatment and low
      heredity. This concept of hebephrenia seems to be more appropriate to demarcate a
      homogeneous subtype which can be the subject of further promising research to
      clarify aetiology and nosology of schizophrenic spectrum psychoses.

PMID- 12516312
TI  - Myers Briggs Type indicator personality profiles in unipolar depressed patients.
AB  - OBJECTIVE: The current study was designed to compare the distribution of Myers
      Briggs Type Indicator (MBTI) personality types in patients with Unipolar
      Depression compared to normative data. METHOD: The MBTI divides individuals into
      four dichotomous types: Extroverted and Introverted, Sensing and Intuitive,
      Thinking and Feeling, and Judging and Perceiving. This yields eight single-factor
      and sixteen four-factor types. One-hundred-thirty Unipolar Depressed patients
      were administered the MBTI-Form F. RESULTS: Unipolar Depressed patients were
      significantly more often Introverted, Sensing, Feeling, and Perceiving single
      factor types respectively, and Introverted-Sensing-Feeling-Perceiving, and
      Introverted-Intuitive-Feeling-Perceiving four-factor types. The male Introverted
      Sensing-Feeling-Perceiving four-factor type was the most dramatically over
      represented. CONCLUSION: The MBTI effectively discriminates a patient group with
      Unipolar Depression from a normative population.

PMID- 12516313
TI  - ADHD and conduct disorder: an MRI study in a community sample.
AB  - MRI studies of children with Attention-Deficit Hyperactivity Disorder (ADHD) have
      consistently attributed core deficits of inattention and impulsivity to frontal
      striatal-cerebellar abnormalities; however, no study has investigated the
      neuroanatomical characteristics of children with ADHD and Conduct Disorder (CD).
      This study examined a community sample of 12 children with combined subtype ADHD
      (aged 8-12, 7 with CD) and 19 healthy controls matched for age, gender,
      handedness and poverty. Volume measurements, including left/right asymmetries,
      were quantified from MRI of the total brain, caudate and cerebellar vermis. No
      significant differences in total brain volume, caudate volume, asymmetry of the
      hemispheres or asymmetry of the caudate were found between the groups.
      Measurements of the left and total posterior superior and inferior lobes of the
      vermis, however, indicated smaller volumes for both pure ADHD and co-morbid
      children compared to the controls. Analysis of variance demonstrated no
      significant volumetric differences between the pure ADHD and co-morbid types.
      Prolonged exposure to methylphenidate was associated with caudate volumes. These
      results suggest ADHD and ADHD co-morbid with CD have similar deviant cerebellar
      morphology and replicate previous studies with an epidemiologically derived
      sample.

PMID- 12516314
TI  - Benzodiazepines in schizophrenia: prefrontal cortex atrophy predicts clinical
      response to alprazolam augmentation.
AB  - Benzodiazepines augment clinical responses to neuroleptics in some, but not all,
      treatment-refractory schizophrenic patients; however the biological predictors of
      response have remained unclear. Since patients with prefrontal cortex (PFC)
      volume loss demonstrate exaggerated subcortical dopamine responses to stress, and
      since benzodiazepines curtail stress-induced subcortical dopamine release in PFC
      lesioned animals, we reasoned that patients with PFC volume loss might show
      preferential clinical responses to benzodiazepine augmentation. Five patients,
      who were participating in a larger four-week double-blind study of alprazolam
      augmentation of neuroleptics in treatment-resistant or partially treatment
      resistant schizophrenia, had brain MRI scans prior to entry into the study. MRI
      scans were morphometrically analyzed to yield estimates of PFC grey and white
      matter volumes and PFC cerebrospinal fluid (CSF) volume, and these were
      correlated with clinical responses to alprazolam augmentation. PFC grey matter
      volume (adjusted for overall cranial capacity) was significantly correlated (r =
      0.96, p < 0.01), in the predicted direction, with alprazolam-associated changes
      in total Brief Psychiatric Rating Scale ratings. PFC volume loss may represent a
      biological marker for benzodiazepine responsivity in schizophrenia, although the
      present findings are considered preliminary because of the small sample size.
      Mechanistic considerations and suggestions for future research are discussed.

PMID- 12516315
TI  - Encephalomyelitis disseminata: a rare, but challenging differential diagnosis of
      anorectic disorder.
AB  - The frequent occurrence of psychiatric syndromes in encephalomyelitis disseminata
      is known to obscure its diagnosis. We here report on the case of a 19-year-old
      female patient presenting symptoms of anorexia nervosa and subsequently diagnosed
      as suffering from encephalomyelitis disseminata. High dose corticoid treatment
      resulted in a nearly complete remission of the neurological symptoms as well as
      the normalization of her eating behaviour. Our case report underscores the
      importance of considering 'organic' aetiology in patients with symptoms of
      distinct eating disorders. The clinical course confirms recent findings,
      suggesting that acute inflammation in encephalomyelitis disseminata may induce
      behavioural symptoms, which precede the onset of neurological signs. To our
      knowledge, only one previous case has been reported to date.

PMID- 12516316
TI  - Psychiatric symptoms and Marfan: part of the syndrome or incidental to it?
AB  - The authors report the case of a patient who consulted primarily for depression
      and anxiety and was secondly diagnosed with Marfan syndrome. The question of
      whether psychiatric symptoms are part of the Marfan syndrome or merely incidental
      to it is raised.

PMID- 12516317
TI  - Improving treatment outcomes with a clinical pathway for hysterectomy and
      myomectomy.
AB  - OBJECTIVE: To determine if using a postoperative clinical pathway for women
      having hysterectomy or myomectomy would improve clinical care. STUDY DESIGN: Data
      from the literature and patient focus groups guided development of a clinical
      pathway. Nurses, pharmacists and physicians participated in the development
      process. Implementation relied on accepted quality improvement methods. We used a
      case-control design to compare administrative and clinical data for patients
      managed with (n = 28) and without (n = 28) the aid of the clinical pathway
      between June 1997 and January 1998. RESULTS: Case and control groups did not
      differ in age, race, payer status, severity of illness or procedure type.
      Clinical differences between pathway and nonpathway patients included a mean six
      hour-shorter period of indwelling bladder catheters (P = .019), mean 11-hour more
      rapid return to regular diet (P = .014) and more pain assessments among pathway
      patients (mean, five vs. two; P < .001). There was no significant difference in
      length of stay between groups. Clinicians used the pathway for approximately one
      year, but with personnel changes the pathway gradually fell out of use.
      CONCLUSION: Clinical pathways can improve quality of care, even if they do not
      reduce length of stay. A team approach that focuses on patient concerns during
      pathway development may help ensure that quality improvement, rather than simply
      cost reduction, arises from the use of clinical pathways.

PMID- 12516318
TI  - Factors influencing the detection of uterine cancer by suction curettage and
      endometrial brushing.
AB  - OBJECTIVE: To analyze the factors that influence the detection of uterine cancers
      by Pipelle and Tao Brush endometrial sampling devices. STUDY DESIGN: Seventy-nine
      Pipelle currettages were followed by Tao Brush sampling. The curettage specimens
      were fixed in formalin for histology and reported by surgical pathology, whereas
      the Tao Brush specimens were fixed in CytoRich Red for histology and cytology and
      reported by cytopathology. Uterine size and features of residual tumors were
      obtained from hysterectomy reports. Follow-up for clinically benign cases ranged
      from 16 to 52 months (mean, 33.7; median, 34). RESULTS: There were 10 uterine
      cancers and 9 hysterectomies. Five cases of centrally located adenocarcinoma,
      ranging from 0.4 to 3 cm, were detected by both samplers. Additionally, a Tao
      Brush sampled an adenocarcinoma located near the cornu. An endometrial stromal
      sarcoma found with a Tao Brush was reported as necrotic tissue by Pipelle. Both
      samplers missed a microscopic focus of adenocarcinoma, an in situ adenocarcinoma
      in a polyp and a large leiomyosarcoma. CONCLUSION: The size and type of tumor and
      its location within the uterine cavity, the mechanism of sampling and preparation
      method influence the detection of uterine cancer by the Pipelle and Tao Brush.

PMID- 12516319
TI  - Electives in obstetric/gynecology residencies. Evidence of flexibility.
AB  - OBJECTIVE: To describe the patterns of electives in obstetric and gynecology
      (OB/GYN) residencies. STUDY DESIGN: A cross-sectional survey of all 274 U.S. and
      Canadian residency directors assessed the type and number of electives offered by
      residency programs and correlated these with program characteristics. A separate
      survey evaluated resident satisfaction with electives at the University of
      Cincinnati (UC). RESULTS: Electives were offered by 53.8% of U.S. programs (95%
      CI: 45.2, 60.4), and 92% of electives were offered in the third year. The median
      length was four weeks, and surgical experience was the most common type of
      elective. A larger proportion of Canadian programs offered electives, which were
      of longer duration. The proportion of programs reporting electives did not vary
      with city size, program size or location. Among 29 UC residents, 62% arranged an
      optional elective, 92% were satisfied with the experience, and 5 residents (28%)
      reported that electives influenced their career choice. CONCLUSION: The
      prevalence of electives appears higher than listed in currently available
      directories, although lower than in other primary care residencies.

PMID- 12516320
TI  - Course and outcome of pregnancy in 54 persistently HIV-1-seronegative sex workers
      and their infants.
AB  - OBJECTIVE: To determine the course and outcome of pregnancy in 54 persistently
      HIV-1-seronegative pregnant commercial sex workers (prostitutes). STUDY DESIGN:
      Five hundred twenty-three initially HIV-1-seronegative prostitutes in Manipur,
      India, were studied between 1990 and 1999. Two hundred forty (46%) women
      seroconverted to HIV-1 during the study period. HIV-1 polymerase chain reaction
      with env, nef and vif gene primers was done on 98 persistently seronegative sex
      workers, who remained seronegative after three years of follow-up. Fifty-four of
      these women became pregnant (study group). The course and outcome of pregnancy
      were studied prospectively in 54 persistently HIV-1-seronegative women and
      compared with those in matched HIV-1-seronegative women from the general
      population coming for routine antenatal checkups. RESULTS: In the 54 seronegative
      women (study group) who became pregnant, there were 52 singleton, term vaginal
      deliveries and two emergency cesarean sections for fetal distress. All 54 infants
      had negative viral cultures for HIV-1 at birth. The women remained seronegative
      throughout pregnancy, as did the control group. All 54 infants were breast-fed
      and remained well. CONCLUSION: A small proportion of highly exposed individuals
      may have natural protective immunity to HIV, may be resistant to HIV-1 and may
      have successful outcomes of pregnancy.

PMID- 12516321
TI  - Documentation of amniotic fluid embolism via lung histopathology. Fact or
      fiction?
AB  - OBJECTIVE: To evaluate pulmonary histopathology for confirming amniotic fluid
      embolism. STUDY DESIGN: The Capra hircus (goat) model with fresh, homologous
      amniotic fluid was used. Raw fluid (n = 8), fluid filtered through a 5-microns
      filter (n = 14) and meconium-stained fluid with 1-7% solid debris (n = 7) were
      injected. Three hours after embolization the animals were euthanized and
      specimens collected. Three to five areas of lung were sampled based on the most
      abnormal areas visually. Traditional and special stains were utilized. The study
      protocol was approved by the institutional review board and animal use and care
      committee. Statistical analysis was by chi 2 with Yates correction. Significance
      was defined as P < .05. RESULTS: Amniotic fluid debris (fetal squames, mucin or
      foreign pigments) was found in 10 of 29 animals (34.5%). Debris was found in 7/7
      (100%) of the meconium group, 2/8 (25%) of the raw fluid group and 1/14 of the
      filtered group (7%). The likelihood of finding debris in amniotic fluid embolism
      with meconium-stained fluid was greater than with raw (P < .017) or filtered
      amniotic fluid (P < .001). CONCLUSION: In this animal model, histopathologic
      confirmation of amniotic fluid embolism was an unreliable marker of the event
      except in cases of amniotic fluid embolism involving meconium-stained fluid.

PMID- 12516322
TI  - Episiotomy and perineal repair. An evaluation of resident education and
      experience.
AB  - OBJECTIVE: To describe current training practices and experience with episiotomy
      and perineal repair in obstetrics and gynecology residency programs in the United
      States. STUDY DESIGN: A questionnaire mailed to all directors of accredited
      programs in the United States for distribution to fourth-year residents in their
      last four months of training included 30 questions regarding formal teaching,
      supervision, experience and repair techniques. RESULTS: A total of 297 of 1,177
      (25.2%) residents, representing 47% of programs, responded. The response rates
      for the various program sizes were: 32.0% for < or = 12 residents, 29.5% for 13
      19 residents, 24.6% for 20-24 residents and 18% for > or = 25 residents. Of the
      residents, 59.9% received no didactics on episiotomy repair techniques; 59.3% had
      no formal teaching on pelvic floor anatomy; and 27.7% of third-degree repairs
      were supervised by attending physicians. Of the respondents, 6.8% had repaired >
      20 fourth-degree lacerations and 40.3%, > 20 third-degree lacerations. Ten
      percent of the graduates felt inadequately trained in perineal repair.
      CONCLUSION: This survey of fourth-year residents from 47% of obstetric programs
      indicated that the majority of residents received no formal training in pelvic
      floor anatomy, episiotomy or perineal repair and, when engaged in such
      activities, had limited supervision.

PMID- 12516323
TI  - Role of steroid receptors in the pathogenesis of tubal pregnancy.
AB  - OBJECTIVE: To determine the role of steroid receptors in the pathogenesis of
      tubal pregnancy. STUDY DESIGN: Twenty-two women in the reproductive-age group who
      had undergone salpingectomy because of ectopic pregnancy or sterilization were
      enrolled. The study group consisted of 12 women who underwent salpingectomy for
      ectopic pregnancy. The control group included 10 patients in whom the tubes had
      been removed for elective sterilization. RESULTS: Estrogen receptors were
      detected in 1 (8.3%) tube with ectopic pregnancy and in 10 (100%) normal tubes (P
      = .0001). Progesterone receptors were present in 4 (33.3%) tubes in the study
      group and in all the tubes in the control group (P = .002). CONCLUSION: Our
      findings indicate that a basic cellular component, the steroid receptor, is
      damaged in tubes harboring pregnancy.

PMID- 12516324
TI  - Pseudomonas aeruginosa-infected IUD associated with pelvic inflammatory disease.
      A case report.
AB  - BACKGROUND: While pelvic infection is known to be an infrequent complication of
      intrauterine device (IUD) use, infections are usually related to microorganisms
      introduced at the time of insertion or by sexual contact. CASE: We diagnosed a 35
      year-old woman with an IUD for 6 years with pelvic inflammatory disease (PID) and
      implemented antibiotic therapy. Her clinical course worsened, and exploratory
      surgery revealed a right tuboovarian abscess with multiple loculated pelvic
      abscesses. Culture of the IUD found heavy growth of Pseudomonas aeruginosa.
      CONCLUSION: P aeruginosa has not previously been described in association with
      infections of the upper female genital tract. Double coverage with appropriate
      antipseudomonal agents is essential for proper treatment of pseudomonal
      infections.

PMID- 12516325
TI  - Live birth after treatment of a heterotopic cornual pregnancy with fetal
      intrathoracic KCI. A case report.
AB  - BACKGROUND: Heterotopic pregnancy, in which an ectopic gestation coexists with an
      intrauterine one, occurs more frequently following in vitro fertilization than
      with spontaneous conception. However, it is rare to find an ectopic gestation in
      the interstitial (or cornual) portion of the fallopian tube. This scenario poses
      challenges in diagnosis as well as difficulties in managing the cornual pregnancy
      while maintaining the viability of the intrauterine gestation. CASE: A 29-year
      old nulligravida with stage IV endometriosis completed in vitro fertilization for
      primary infertility. A heterotopic pregnancy involving the right interstitial
      portion of the fallopian tube as well as a viable singleton intrauterine
      pregnancy was diagnosed using serial ultrasound. Successful termination of the
      cornual pregnancy was accomplished by transabdominal fetal intrathoracic
      injection of KCl under ultrasound guidance. CONCLUSION: Pregnancy reduction of a
      heterotopic cornual gestation using KCl is a treatment alternative for this
      uncommon but potentially devastating complication of in vitro fertilization.

PMID- 12516326
TI  - Cavernous lymphangioma of the vulva. A case report.
AB  - BACKGROUND: Lymphangioma is a rare cause of a vulvar mass. Two types of
      lympangioma involving the vulva have been described: lymphangioma circumscriptum
      and cavernous lymphangioma. Cavernous lymphangioma has been reported much less
      frequently than lymphangioma circumscriptum in association with the vulva. CASE:
      A cavernous lymphangioma was diagnosed in a 19-year-old nullipara who had a
      history of a gradually expanding vulvar mass. The mass was removed surgically,
      with no postoperative complications or recurrences to date. CONCLUSION: Cavernous
      lymphangioma should be considered in the differential diagnosis of a vulvar mass
      and can be treated successfully with surgical excision.

PMID- 12516327
TI  - Uterine rupture in an unscarred uterus after application of fundal pressure. A
      case report.
AB  - BACKGROUND: Rupture of an unscarred uterus is rare, with a reported incidence of
      1 in 8,000-15,000 pregnancies. We report a case occurring during labor. CASE: A
      33-year-old woman, gravida 3, para 0, abortion 2, was admitted at 40 weeks'
      gestation with ruptured membranes. Fundal pressure was applied during delivery
      due to maternal exhaustion. Uterine rupture was diagnosed from palpation of the
      fetal extremities coupled with a decreased fetal heartbeat. A 6-cm transverse
      laceration was discovered over the lower uterine segment during emergency
      cesarean section. The uterus was sutured. There were no further complications,
      and the postoperative course was uneventful. CONCLUSION: Spontaneous rupture of
      the unscarred uterus during labor is rare, with only one case recorded at our
      institution over a 10-year period. Risk factors include weakness of the uterine
      muscle and the application of fundal pressure. Early detection and immediate
      surgical intervention are the mainstays of management.

PMID- 12516328
TI  - Diagnosis and management of abdominal pregnancy. A case report.
AB  - BACKGROUND: Abdominal pregnancy is a rare obstetric emergency, occurring in 1 in
      10,000 pregnancies. CASE: An 18-year-old woman, gravida 3, para 1, presented for
      evaluation of an abnormal level of maternal serum alpha-fetoprotein.
      Transabdominal ultrasound examination revealed absence of amniotic fluid with
      limited imaging ability. Transabdominal amnioinfusion was done to better
      visualize the fetus. A small uterus was seen in the pelvis, and an abdominal
      pregnancy was identified with the placenta attached anteriorly over the right
      pelvic sidewalls. After delivery of the fetus, the placenta was left in situ. The
      patient recovered postoperatively and was doing well a year after the procedure.
      A 12 x 10-cm mass remains over the right pelvic sidewall without detectable
      Doppler blood flow. CONCLUSION: State-of-the-art imaging and prenatal diagnostic
      techniques allowed correct diagnosis, adequate preparation and optimal management
      of this dangerous condition.

PMID- 12516329
TI  - Hemodialysis for toxic hypermagnesemia caused by intravenous magnesium in a woman
      with eclampsia and renal insufficiency. A case report.
AB  - BACKGROUND: Toxic hypermagnesemia is a wellknown adverse effect of intravenous
      magnesium. CASE: A woman with postpartum eclampsia was treated with intravenous
      magnesium at another hospital and then transferred to our hospital due to
      cardiopulmonary failure. Blood magnesium and creatinine levels were markedly
      elevated. Hemodialysis rapidly improved her condition. CONCLUSION: Hemodialysis
      is effective for toxic hypermagnesemia caused by intravenous magnesium in a case
      of severe renal insufficiency.

PMID- 12516330
TI  - Mosaic form (45X/46XX) of Turner's syndrome. A case report.
AB  - BACKGROUND: Turner's syndrome (TS) is a sex chromosome disorder occurring in 1 in
      2,500 female births and in approximately 50 in 100,000 adult females and is
      characterized by retarded growth, gonadal dysgenesis and infertility. The
      45,X/46,XX chromosomal pattern is the most frequent mosaic type of this disease
      (36%). CASE: The mosaic form of TS was diagnosed in a 25-year-old, nulliparous
      woman whose major symptoms were menstrual irregularity and menorrhagia. She had
      normal development of secondary sexual characteristics and spontaneous menarche
      despite a very low amount (7%) of normal cells. CONCLUSION: Dysfunctional uterine
      bleeding is very uncommon in TS. Mosaic forms of TS may have very few features of
      TS despite a very low range of normal cells.

PMID- 12516331
TI  - [Arterial hypertension syndrome as a maladaptation marker].
AB  - Hypertension epidemic in all developed countries is stipulated by incidence of
      primary hypertension. All prophylactic measures and pharmacotherapy are designed
      just for prevention and therapy of this hypertension form making up the majority
      of easy cases and unfavorable hypertension cases. The experience of western
      countries demonstrates the efficiency of purposeful population strategy in
      prophylaxis of hypertension and prevention of its complications in patients and
      in high risk groups with successful prevention of chronic hypodynamia,
      restriction of dietary salt, refusal of smoking and abuse of alcohol. Some
      patients also need treatment of dislipidemia and prophylaxis of thromboses with
      antiaggregant agents.

PMID- 12516332
TI  - [Psychosomatic aspects of gastrointestinal diseases].
AB  - The article covers up-to-date information about the incidence of psychosomatic
      pathology among patients of gastroenterologic profile including patients with
      gastroesophageal reflux disease and syndrome of irritable colon. From the point
      of view of psychosomatic idea the article considers the factors predisposing,
      permitting and retarding the development of the disease. A detailed description
      is available in psychosomatic disturbances, modern concepts about their
      pathogenesis including a break of correlation between limbic and frontal regions
      of central nervous system and disorder in serotonin metabolism--clinical
      manifestations, methods of diagnosis and treatment including selective inhibitors
      and stimulators of serotonin reuptake and neuroleptics.

PMID- 12516333
TI  - [Sleep apnea syndrome].

PMID- 12516334
TI  - [Syndrome of secondary immunodeficiency: pathogenesis and approaches to
      treatment].

PMID- 12516335
TI  - [Comparative long-term outcomes of balloon angioplasty of uni- or multi-vessel
      lesions in coronary disease].
AB  - A study has been carried out on long-term results of transluminal balloon
      angioplasty (TLBAP) in case of mono- and multivascular lesion of coronary bed
      (CB). During long-term follow-up (16.3 +/- 3.8 months) a high survival rate was
      observed after treatment procedure both in mono- (97.1%) and multivascular
      (98.75%) lesion. However, patients with monovascular lesion had lesser
      probability of being subjected to additional revascularization procedure and
      greater probability of avoiding angina pectoris in long-term follow-up unlike
      patients with multivascular lesion of coronary arteries (85.7% vs 63.8%). At the
      same time a good angiographic angioplastic effect of dilated vessel remained in
      equal number of patients: 66.7% with monovascular lesion and 68.6% with
      multivascular lesion. Therefore, it is advantageous to use TLBAP both in mono-
      and multivascular CB lesion.

PMID- 12516336
TI  - [Characteristics of cerebral microembolic signals and focal lesions of the brain
      in different causes of cardiogenic embolism].
AB  - To study quantitative and qualitative characteristics of microembolic signals
      (MES) and specific features of a focal damage to the brain depending on the site
      of the embolic substrate in patients with cardioembolic stroke (CES), we examined
      84 patients who survived CES. 38 (45.2%) of them had an acute stage, 46 (54.8%)-
      a residual stage. Group 1 comprised 42 patients with cardial pathology
      characterized by intrachamber formation of the embolus and 2 patients with an
      open oval window. Group 2 consisted of 40 (48%) patients with diseases promoting
      formation of emboli on the cardiac valves. The highest frequency, intensity and
      duration of MES in CES were registered in patients of group 2 while the number of
      ischemic focuses was greater in patients of group 1. This may be explained by the
      fact that intensity and duration of cardiogenic MES depend more on acoustic
      density of the embolus than on its size. Therefore, the site of the embologenic
      substrate together with quantitative and qualitative MES characteristics is the
      key factor of a high risk of cardiocerebral embolic complications.

PMID- 12516337
TI  - [Macro- and trace elements of blood in elderly patients with bronchial asthma].
AB  - Using the method of roentgen fluorescent analysis a study was carried out on the
      content of macro- and trace elements (ferrum, zink, sulfur, potassium, calcium)
      in whole blood and serum of 62 women with bronchial asthma (BA) depending on
      severity of the disease and performed therapy. The study revealed a disrupted
      content of studied chemical elements in serum and whole blood of patients having
      BA of various severity: reduction in the level of sulfur and potassium and
      increase of ferrum and zink proportionally to the severity of process. At the
      same time calcium ions redistributed from serum to blood cells. A high
      concentration of chemical elements in whole blood was observed in patients who
      had received systemic glucocorticoids (GC) as basic therapy compared with
      patients treated with inhalation GC.

PMID- 12516338
TI  - [Effects of local vibration on development of ischemic heart disease in miners of
      South Kuzbas].
AB  - The incidence of ischemic heart disease (IHD) and risk factors of its genesis
      have been studied in 380 miners of a control group non-exposed to industrial
      vibration. Constitution type and a number of phenotypic signs have been
      determined for all examined workers with hemostatic indices defined in 60 miners
      before and after the performance of vibrational load test. High incidence of IHD,
      arterial hypertension and hyperholesterolemia have been detected in the miners
      working with vibration instruments and hemostatic disorders predisposing to
      ischemic heart disease have been revealed. In the miners of vibrodangerous
      occupations suffering from ischemic heart disease, hypersthenic constitution type
      determined by Rees-Eysenc index less than 92.2 and the height below 170 cm was
      found to occur more frequently.

PMID- 12516339
TI  - [Clinical and medicinal cost-effect assessment of effectiveness of empirical
      therapy of extra-hospital pneumonia in hospital setting].

PMID- 12516340
TI  - [Content of calretinin-immunoreactive epitheliocytes of the stomach in patients
      with chronic gastritis and peptic ulcer].
AB  - The article covers the information about 50 patients with gastric ulcer (GU) and
      110 patients with duodenal ulcer (DU). 60 healthy persons and 70 patients with
      chronic helicobacter gastritis (CHG) formed comparative groups. Calretinin
      immunoreactive epitheliocytes in antral region's gastric mucous membrane were
      reaved by clinical-endoscopic morphological and immunohistochemical
      investigations. It is shown that hyperplasia of calretinin-immunoreactive cells
      is in CHG cases. On the contrary, in DU and GU there is hypoplasia of calretinin
      immunoreactive cells. Diametrically opposed data on quantitative description of
      focused endocrine cells in patients with CHG and peptic ulcer disease permitted
      to make a conclusion about the importance of calretinin-immunoreactive cells in
      peptic ulcer. The results of the investigation made it possible to give the
      prognostic appreciation of CHG course and its transformation into peptic ulcer
      disease.

PMID- 12516341
TI  - [Effectiveness of an intensive pelobalneotherapy course in the treatment of
      patients with duodenal ulcer].
AB  - Intensification of peloidobalneation pattern results in cicatrization of ulcer in
      many patients with duodenal ulcer at the stage of partial clinical remission and
      attenuated exacerbation during 18 days promoting alleviation in chronic
      inflammation in gastroduodenal zone.

PMID- 12516342
TI  - [Disorders of protein C anticoagulant system in various clinical conditions].
AB  - A study was carried out on activity of protein C4 in 73 surgical patients
      (coagulation test, reagents of company PEHAM). The reduction in activity of
      protein C was observed in patients with focal liver lesion related to disturbance
      of protein formation function. This percent of disturbances in protein C system
      is more often found in patients with vascular pathology. This is explained by the
      mechanism of its action and implication of vascular endothelium into the process.
      Disturbances in patients with injury infection are stipulated with activity of C
      and S proteins and availability of mutant factor V--factor Leiden in patients
      with diabetes. In the first days after surgical intervention the activity of C
      protein was much reduced. The obtained results emphasize the importance of
      research in the system of protein C in surgical patients.

PMID- 12516343
TI  - [Monotherapy with recombinant interleukin-2 (ronkoleukin) for chronic hepatitis
      C].
AB  - For the last few years substantial disturbances of cellular immunity have been
      revealed in patients with chronic hepatitis "C" (CHC). It was found out that the
      progression of the disease is closely related with insufficient number and
      inadequate function of specific CD4+ lymphocytes. Other than this, substantial
      disturbances of interleikin-2 (IL-2) were detected in CHC patients. This fact
      served as a basis to carry out a comparative study on two schemes of injecting
      recombinant interleukin-2 (Ronkoleikin) to CHC patients. 8 min units of this
      preparation (in the doze of 500,000 units 2 times a week during 8 weeks) were
      injected to patients of the 1st group and 12 min units (Ronkoleikin was injected
      3 times per week) to patients of the 2d group. It was found that two injection
      schemes were tolerated satisfactorily. A full therapeutic effect was observed in
      80% of patients in the 1st group and in 10% of cases in patients of the 2d group.
      The 2d scheme of Ronkoleikin provided a statistically significant and steady
      increase in the number of CD4+ cells (from 457 +/- 47 to 763 +/- 123 c/mcl) and
      CD+8 lymphocytes (from 338 +/- 52 to 520 +/- 73 c/mcl).

PMID- 12516344
TI  - [Use of ascorbic acid for raising clinical response to long-acting nitrates].
AB  - The data of clinic observation and ECG-monitoring show that ascorbic acid
      significantly increases antianginal vasodilatory effects of nitroglycerine thus
      preventing from development of ischemic miocardial reaction in response to
      complamin injection. Incubation under anaerobe conditions of ascorbic acid
      solution with NO-donors (sodium nitrate, nitroglycerine) or with the blood of
      ischemic patients who had been treated for a long time with long-acting
      nitrovasodilators, results in liberation in Varburg vasculium of gas bubbles
      identified as nitrogen oxide according to hemoglobin nitrosylation. Activation of
      endogen NO-donors with ascorbic acid and taking antilogs of antianginal effects
      of exogenous nitroglycerine makes it possible to substantially increase the
      efficiency of nitratotherapy and nitratoprophylaxis of angina pectoris.

PMID- 12516345
TI  - [Differential diagnosis of ischemic heart disease in patients with associated
      atherosclerotic lesions].
AB  - The diagnosis and differential diagnosis of attendant ischemic heart disease
      (IHD) was conducted in 65 men (age 49-74 years) with Takayashu's syndrome and 59
      men (age 39-64 years) with associated atherosclerotic lesions of the arch
      branches and the abdominal portion of the aorta. The examination was performed
      using velo- and spiroergometry, echocardiography, drug tests,
      coronaroventriculography. IHD was diagnosed in 38.4% patients with aortic arch
      lesions and in 44.1%--in associated lesions. The majority of the patients were
      referred to functional class III and IV. The above complex use of diagnostic
      methods allows objective evaluation of diagnostic data, IHD severity, adequate
      decision on the treatment policy.

PMID- 12516346
TI  - [Psychopathological aspects of pain syndrome in somatoform disorders].
AB  - Basing on the data on patients in situation of somatogenic vital threat,
      essential psychogenic grounds of chronic pain syndrome are shown which negatively
      affects psychogenic adaptation and rehabilitation, deteriorates quality of life.
      Addition of antidepressants in routine therapy of somatic patients improves
      psychic status of patients, reduces pain syndrome, raises effectiveness of
      rehabilitation.

PMID- 12516347
TI  - [Clinical manifestations of neuroendocrine tumors].
AB  - A complex clinico-functional morphologic examination was carried out on 125
      patients with neuroendocrine tumors (NET): carcinoids, pheochromocytoma and
      multiple endocrine adenomatosis (an integral part of which is pheochromocytoma,
      gastrinoma and medullar C-cell carcinoma of thyroid gland). There was a clinical
      examination using laboratory and instrumental methods in pre- and postoperative
      periods, morphological research of removed tumors. According to the obtained
      indications, selective angiography and static scintigraphy with 111Tc was carried
      out. Isotopes 111-In were used in 3 patients for scintigraphic research of
      somatostatinpositive NET. The following versions were selected: serotonin and
      sympathoadrenal clinical variants of monoaminoforming NET, clinical versions of
      multiple endocrine neoplasias, a clinical version of adenocarcinomas having in
      their composition cells with neuroendocrine differentiation accompanied by
      neuroendocrine paraneoplastic syndrome. There were offered a term and definitions
      of hyperproduction syndrome of regulatory peptides in case of NET.

PMID- 12516348
TI  - [Thymus lipoma complicated by pulmonary artery thromboembolism].
AB  - Combination of mediastinum thymolipoma (rare benign variety of thymus tumor) and
      chronic thrombosis of the main trunk and branches of pulmonary artery is a
      relatively rare but not occasional combination (location of the tumor in the zone
      of vascular fascicle, impediment of diastolic heart function because a tumor
      being equal to the heart enveloped pericardium) resulting in lethal outcome of
      patient at young age.

PMID- 12516349
TI  - [Diagnostic errors of peripheral lymphadenopathy in HIV-infection].

PMID- 12516350
TI  - [Syphilis lesions of the stomach].
AB  - The paper describes a syphilitic lesion of the stomach in a man who for the first
      time consulted therapeutist and gastroenterologist with symptoms similar to
      stomach tumors. A possible infection took place during diagnostic
      fibrogastroscopy (FGS). Reiterated FGS did not permit endoscopists to suspect
      syphilis. The data of roentgenography fell into the pattern of stomach cancer.
      After additional examination with performance of specific seroreactions, an early
      latent syphilis was diagnosed. The treatment resulted in full clinico-serologic
      regression of the disease. A timely detection of syphilitic stomach lesion is a
      great problem if clinical manifestations are estimated separately from anamnestic
      data.

PMID- 12516351
TI  - [Systemic AL-amyloidosis with extensive pulmonary and vascular lesions].
AB  - Here is an observation data on systemic AL-amiloidosis with primary lesion of
      lungs and vessels (a false hemorrhagic syndrome, ischemic insult in the region of
      middle cerebral artery). At the same time lesions of kidneys and heart became of
      minor significance. Amiloid lesion of lungs was characterized by unusual
      combination of symptoms: a galloping hydrothorax, a vast focus in the
      consolidation of pulmonary tissue with focuses of calcification, relapsing
      pneumothorax.

PMID- 12516352
TI  - Is your narcotics practice 'significantly different?'.

PMID- 12516353
TI  - Unlicensed nurse-practitioner fails to diagnose cardiac condition-death. Case on
      point: Wellstar Health Systems, Inc. v. Green, 2002 WL 31324127 S.E.2d -GA.

PMID- 12516354
TI  - LA: nurse says "Take aspirin & call Dr. in A.M.:" complications arise from delay
      in treatment.

PMID- 12516355
TI  - MI: obese patient injured by errant injection: was nurse's expert testimony
      admissible?

PMID- 12516356
TI  - RN has latex allergy: 'recurrence' or 'aggravation?' Case on point: St. Luke's
      Midland Reg. Med. Ctr. v. Kennedy, 2002 WL 31521401 N.W.2d -SD.

PMID- 12516357
TI  - Gift giving.

PMID- 12516358
TI  - New in disease prevention: the adult immunization schedule.

PMID- 12516359
TI  - Glimpses on a segment of history in SDSMA.

PMID- 12516360
TI  - Ebers Papyrus case #873: a probable case of neurofibromatosis 1.

PMID- 12516364
TI  - [Potential antimitotics. 2. Synthesis of 1-benzyl-3-carbethoxy-2-quinolones].
AB  - A group of substituted 1-benzyl-3-carbethoxy-2-quinolones, whose design was based
      on the structures of well established antimitotics, were synthesized by a three
      reactions sequence. Although the yields of the first reaction (condensation of o
      nitrobenzaldehydes with diethyl malonate) could not be improved, the synthetic
      route turned out quite efficient.

PMID- 12516365
TI  - [Infrared laser photochemistry of metal carbonyls in the presence of
      cyclopentadiene].
AB  - Mixtures of C5H6 and Fe(CO)5, Cr(CO)6, and Co2(CO)8 were irradiated in the
      gaseous phase with the P-20 line (944.21 cm-1) of a CW CO2 laser using SF6 as a
      sensitizer. The reaction products were metal particles and carbon monoxide, and
      in the C5H6/Fe(CO)5/SF6 mixture the iron dimer (C5H5)2Fe2(CO)4 was isolated.

PMID- 12516369
TI  - [Effects of skeletal muscle proteins on corrosion of stainless steels].
AB  - The corrosion behavior of AISI 304 and AISI 316 stainless steels and a steel that
      matches the requirements of the ASTM Standard F-138 of possible use in
      traumatology, was studied in the presence of skeletal muscle proteins. The
      investigation was carried out using potentiodynamics polarization measurements
      and cyclic polarization, using a fluid of the same protein and salt composition
      than skeletal muscle. To evaluate the effect of the proteins, the tests were
      performed with and without the addition of proteins to the cellular fluid at 37
      degrees C. The electrochemical assays revealed a negative effect of proteins on
      pitting corrosion, according to the quality of the steel used to carry out the
      assays; the most resistant being the AISI 316L and the F-138. In the presence of
      proteins scanning electron microscopy (SEM) carried out after cyclic polarization
      revealed a mixed layer, formed by oxides and proteins stuck to the metal surface.
      This layer seems to be a more unstable passive layer than the corresponding one
      formed in the absence of proteins. The Tafel plot in the presence of proteins
      revealed that the corrosion mechanism was controlled by diffusional process. The
      results with respect to pitting corrosion were similar to those obtained in
      marine environments.

PMID- 12516370
TI  - Features of retracted (atelectatic) and ballooned (hyperectatic) tympanic
      membranes.

PMID- 12516371
TI  - Vertical insertion of the middle turbinate: a sign of the presence of a well
      developed agger nasi cell.

PMID- 12516372
TI  - Value of the 70 degrees telelaryngoscope in microlaryngoscopy for benign
      pathology.

PMID- 12516373
TI  - An encephalocele as a complication of mastoid surgery.

PMID- 12516374
TI  - Esophagitis with an inflammatory polyp.

PMID- 12516375
TI  - Caloric test findings in a patient with recurrent disequilibrium.

PMID- 12516376
TI  - Nodular fasciitis.

PMID- 12516377
TI  - Rapid growth of acoustic neuromas after stereotactic radiotherapy in type 2
      neurofibromatosis.
AB  - We describe a rare complication of stereotactic radiotherapy for large acoustic
      neuromas in a patient with type 2 neurofibromatosis. We retrospectively reviewed
      the case of a 14-year-old girl who had been referred to our tertiary care center.
      Prior to referral, the patient had been evaluated for hoarseness. During the work
      up, magnetic resonance imaging (MRI) detected two large bilateral acoustic
      neuromas and two bilateral jugular foramen tumors. The patient was diagnosed with
      type 2 neurofibromatosis, and she underwent stereotactic radiotherapy for
      treatment of the two acoustic neuromas; the jugular foramen tumors were not
      irradiated. The patient's post-treatment course was complicated by hydrocephalus
      and symptoms of brainstem compression, which required urgent surgical
      intervention. Follow-up MRI 7 months following radiotherapy demonstrated a rapid
      growth of the acoustic neuromas, but no appreciable change in the size of the
      jugular foramen neuromas. These findings suggest that the radiotherapy might have
      been the cause of the rapid growth of the acoustic neuromas. To our knowledge, no
      such report has been published in the literature, and this phenomenon might be
      unique. Our findings suggest that radiotherapy might not be the optimal first
      line treatment for acoustic neuromas in patients with type 2 neurofibromatosis.

PMID- 12516378
TI  - Study of surgeons' agreement on the presence of bony anomalies on coronal CT of
      paranasal sinuses.
AB  - We conducted a study to determine the level of agreement among five surgeons who
      assessed the surgical risk to key neighboring structures prior to endoscopic
      sinus surgery as depicted on coronal computed tomography (CT). The five observers
      studied preoperative CT scans that had been performed on 29 patients. Two scoring
      systems were used to rate each scan; the Lund-Mackay system and our own risk
      assessment system. Kappa analysis was used to measure interobserver agreement. We
      found that the overall level of agreement among the five surgeons according to
      the Lund-Mackay criteria was moderate, while agreement according to our risk
      assessment system was only slight. We conclude that surgeons' agreement on the
      bony detail of risk structures is not as strong as our agreement on other
      factors, such as staging disease.

PMID- 12516379
TI  - Synchronous parotid and nasopharyngeal Warthin's tumors: first report of a case.
AB  - Only a few isolated reports of Warthin's tumor of the nasopharynx have been
      published in the literature. None of the patients cited in those reports had
      another Warthin's tumor elsewhere. We describe the case of a patient who had
      synchronous nasopharyngeal and parotid Warthin's tumors--a case that we believe
      is the first to be reported in the literature. Our case provided us with a unique
      opportunity to study and compare the two tumors in a single patient. Their
      simultaneous presence might have been more than coincidental; it is possible that
      these two tumors were the result of the influence of one or more unknown systemic
      factors on trapped salivary elements in the lymphoid stroma.

PMID- 12516380
TI  - An unusual case of primary nasal tuberculosis with epistaxis and epilepsy.
AB  - Primary nasal tuberculosis is rare. We report a case that was all the more
      extraordinary because of the age and sex of the patient (an 11-year-old boy), the
      unusual associated symptoms (epistaxis and grand and seizures), and the presence
      of intracranial extension. Clinical and radiologic findings on our initial
      evaluation suggested that the patient had a large sinonasal malignancy. The
      patient manifested no evidence of pulmonary tuberculosis. The diagnosis of
      primary nasal tuberculosis was established only after we obtained the results of
      histopathology of the excised mass and a subsequent tuberculin skin test; the
      diagnosis was confirmed by the patient's rapid response to antituberculosis drug
      therapy. We also review the relevant literature on this rare condition.

PMID- 12516381
TI  - Facial paralysis caused by malignant skull base neoplasms.
AB  - OBJECT: Bell palsy remains the most common cause of facial paralysis.
      Unfortunately, this term is often erroneously applied to all cases of facial
      paralysis. METHODS: The authors performed a retrospective review of data obtained
      in 11 patients who were treated at a university-based referral practice between
      July 1988 and September 2001 and who presented with acute facial nerve paralysis
      mimicking Bell palsy. All patients were subsequently found to harbor an occult
      skull base neoplasm. A delay in diagnosis was demonstrated in all cases. Seven
      patients died of their disease, and four patients are currently free of disease.
      CONCLUSIONS: Although Bell palsy remains the most common cause of peripheral
      facial nerve paralysis, patients in whom neoplasms invade the facial nerve may
      present with acute paralysis mimicking Bell palsy that fails to resolve. Delays
      in diagnosis and treatment in such cases may result in increased rates of
      mortality and morbidity.

PMID- 12516382
TI  - Applications of the diode laser in otolaryngology.
AB  - We undertook a study to determine the usefulness and effectiveness of a
      relatively new, portable 980-nm wavelength diode laser with a fiberoptic delivery
      system. We tested the laser in several clinical situations, both in the operating
      room and in the office. We used it while performing 14 turbinate reduction
      procedures, one nasal polypectomy, one ablation of an oral papilloma, and one
      photocoagulation of nasal telangiectasias. Our preliminary findings indicate that
      the use of this laser was helpful in alleviating nasal congestion in the patients
      with turbinate dysfunction and in controlling epistaxis in the patient with
      telangiectasias. It was also effective in treating the polyp and papilloma
      patients. We did not experience any intra- or postoperative complications. The
      laser's flexible fiber delivery system is compatible with hollow instruments,
      allows for coaxial vision, and is ideally suited for intranasal use. Its
      portability and functional diversity make it an attractive alternative to the
      conventional carbon dioxide, argon, and neodimium:yttrium-aluminumgarnet lasers.

PMID- 12516383
TI  - Blastomycosis of the vocal folds with life-threatening upper airway obstruction:
      a case report.
AB  - Blastomycosis is a chronic fungal disease that primarily affects the lower
      respiratory tract. The acute inflammatory phase of the primary pulmonary
      infection is characterized by a lymphohematogenous spread to extrapulmonary
      sites, especially the skin. The presence of disseminated infection with
      Blastomyces dermatitidis in the larynx is unusual. In areas of the United States
      where this fungus is endemic, failure to consider laryngeal involvement might
      lead to inappropriate therapy and thus worsening inflammation and airway
      compromise.

PMID- 12516384
TI  - Prognostic factors in mortality and morbidity in patients with differentiated
      thyroid cancer.
AB  - We attempted to determine if women younger than 45 years of age who have isolated
      papillary thyroid cancer and whose tumors are smaller than 4 cm (T2N0M0) are at
      low risk for mortality and morbidity following thyroid lobectomy. To this end, we
      analyzed information on both women and men obtained from our review of the
      literature, and we integrated it with data compiled in the Delaware Cancer
      Registry. We performed a secondary analysis to determine if the risk of death and
      recurrence can be predicted on the basis of age, tumor size, sex, histology, and
      the type of operation. We found that among patients who had undergone either
      thyroid lobectomy or total thyroidectomy, mortality rates were 1.3% for those
      younger than 45 years of age and 15.6% for those 45 years and older (p < 0.0001).
      With respect to tumor size, patients whose masses were smaller than 4 cm had
      significantly lower mortality (3.0%) and recurrence (11.1%) rates than did those
      whose tumors were 4 cm or larger (16.8 and 33.3%, respectively; p < 0.0001).
      Other significant risk factors for death were male sex and the presence of
      follicular thyroid cancer (as opposed to papillary thyroid cancer). The risk of
      permanent hypocalcemia was significant among patients who had undergone total
      thyroidectomy, but not among those who had been treated with lobectomy. The
      subgroup of patients who had the lowest risk of mortality and morbidity was made
      up of women younger than 45 years years who had a papillary thyroid tumor smaller
      than 4 cm that was limited to one lobe and who had undergone lobectomy. On the
      other hand, we found that lobectomy might carry a higher risk of recurrence (from
      a micrometastasis in the cervical lymph node) than does total thyroidectomy.
      Experienced surgeons whose rates of hypocalcemia and recurrent laryngeal nerve
      paralysis following total thyroidectomy are low offer their patients the
      unambiguous advantage of superior follow-up with thyroglobulin and radioactive
      iodine.

PMID- 12516385
TI  - [Priapism in the stallion].
AB  - A review of the literature is given concerning the anatomy and pathophysiology of
      the equine penis with regard to priapism: a prolonged erection of the penis not
      associated with sexual arousal. Several treatment options, such as flushing of
      the corpus cavernosum penis with heparinized saline and the creation of shunt
      between the corpus cavernosum penis and the corpus spongiosum penis are
      discussed. Subsequently, a case of priapism in a stallion following the injection
      of acepromazine, is discussed. The priapism resolved after the corpus cavernosum
      penis was flushed with the stallion under general anaesthesia.

PMID- 12516386
TI  - [Senecio jacobaea: deceiving beauty. Senecio jacobaea poisoning].
AB  - In a cattle herd problems were noticed during 1.5 years, characterised by
      emaciation and loss of milk production with lower fat- and protein%, tenesmus,
      central nervous symptoms (aggression, circling and blindness), diarrhoea, eczema
      solare and death. Clinical, laboratory and post mortem examinations did not
      reveal a specific cause at first. An intoxication was suspected based on the
      clinical symptoms, the course of the disease in sick animals and severe liver
      cirrhosis found in a sudden death cow: The animals were fed grassilage derived
      from an air force base on which an overwhelming amount of tansy ragwort (Senecio
      jacobaea) was present. On subsequent microscopic examination of the livers of 11
      slaughtered clinically healthy animals all of these showed fibrosis in varying
      extension. Cirrhosis and fibrosis of the liver and the clinical symptoms are all
      features of chronic pyrrolyzidine alkaloidosis. Tansy ragwort poisoning has not
      been diagnosed in the Netherlands for years. The rise in cases is due to more
      extensive use of land.

PMID- 12516387
TI  - [Reaction to "Bovine spongiform encephalitis: the importance of one European
      ruling"].

PMID- 12516388
TI  - [Inject and protest].

PMID- 12516389
TI  - [Punishment and discipline tribunal go hand in hand in development of norms].

PMID- 12516390
TI  - [Discipline tribunal? Yes! But with the correct rules!].

PMID- 12516391
TI  - [Effect of baicalin and dexamethasone on cytokines in brain tissue of infectious
      brain edema].
AB  - OBJECTIVE: To explore the effect of baicalin(BC) and dexamethasone(DXM) on
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha(TNF-alpha) in
      brain tissues of infectious brain edema. METHODS: The infectious brain edema
      model induced by pertussis bacilli(PB) was used. Brain water content(WC), content
      of Na+ and the levels of IL-1 beta, TNF-alpha were determined, and the
      morphological changes were observed under the light microscope. RESULTS: The
      results showed that the levels of WC, Na+, IL-1 beta and TNF-alpha in group PB
      were higher than those in group of normal saline(NS) (P < 0.01). And they were
      lower in groups BC and DXM than those in group PB(P < 0.05). In groups BC and
      DXM, there were no significant difference in the contents of water, Na+, IL-1
      beta and TNF-alpha(P > 0.05). The water contents were positive linar correlated
      with IL-1 beta or TNF-alpha(P > 0.05). The water contents were positive linear
      correlated with IL-1 beta or TNF-alpha contents(r = 0.9381, 0.8349, P < 0.01).
      The structure of brain tissues in group NS was normal. In group PB, there were
      severe edema in brain tissues. In groups BC and DXM, the edema of brain tissues
      was reduced. CONCLUSIONS: The results suggest that the protective effect of BC
      and DXM against infectious brain edema were similar, the mechanism may be
      associated with the reduction of TNF-alpha and IL-1 beta.

PMID- 12516392
TI  - [Immunoscreening of Schistosoma japonicum adult worm cDNA library by sera from
      rabbits vaccinated with ultraviolet-attenuated cercariae].
AB  - OBJECTIVE: To find out the major antigenic molecules of radiation-attenuated
      cercariae, and provide some useful candidate antigens for developing
      schistosomiasis vaccine. METHODS: Schistosoma japonicum (Sj) adult worm cDNA
      library was screened by sera of rabbits vaccinated with ultraviolet-attenuated
      cercariae, and the inserts of positive clones were specifically amplified by PCR
      and sequenced. RESULTS: Ten positive clones were obtained after three rounds of
      screening, and the size of Sj cDNA fragments of the positive clones ranged from
      1.5 kb to 1.8 kb. Five partial sequences were got after preliminary sequencing.
      Two of them had significantly homology with Sj dynein light chain 5(DLC 5) gene
      and Sj mitochondrial gene, respectively, and the others were identified as
      partial sequences of novel genes for they showed only partial homology with non
      schistosome genes or other organism in the database. CONCLUSIONS: The positive
      clones may be the genes encoding the antigens that can elicit protective immunity
      against Sj.

PMID- 12516393
TI  - [Establishment of the data base of large human sperm bank and its application].
AB  - On the basis of Access 97, we set up the first computer management system for
      human sperm bank in China, which dealt with various information and data of sperm
      bank and of treatment for AID(artificial insemination donor) patients. The system
      and its application, characteristics and significance were discussed in this
      article.

PMID- 12516394
TI  - [Innervation of medial olivocochlear efferents in the cochlea of gerbils].
AB  - To explore the distributions of the medial olivocochlear (MOC) fibers and
      terminals in the cochlea of Mongolian gerbils and their physiological
      significance, a quantitative study on the distribution of MOC efferent fibers and
      terminals in whole cochlea of gerbils was performed using histochemical staining
      of acetylcholinesterase in the surface preparations. The relation between the
      density and size of MOC fibers and terminals in the cochlea and cochlear place
      frequency map was analysed. The results were that the MOC fibers and terminals
      unevenly spreaded in the cochlea; the densest and the thickest MOC fibers and
      terminals were found in the distal part of the base turn and the second turn.
      These results demonstrate that the distribution of MOC fibers and terminals in
      the cochlea of gerbils is closely related to the function of frequency analysis
      of the cochlea.

PMID- 12516395
TI  - [Characteristics of an established cervical carcinoma cell line HCE1].
AB  - This paper deals with a new cell line established from 5 carcinoma specimens of
      hysterectomy and designated as HCE1. This cell line has been passaged more than
      80 times(more than 18 months). It has the characteristics: 1. The pathological
      features of the tumor transplanted in nude mice were similar to that of the
      original inoculated lesion; 2. Electromicroscopically, there were rich microvilli
      on the surface of the cells. Abundant ribosomes were also observed; 3. The growth
      curves of the 25th passage were determined, the population doubline time
      calculated in the log phase of growth was 45.8 h; 4. The cloning efficiency in
      soft agar averaged 14.8% after counting 6 plates; 5. Karyo-type analysis showed
      aneuploidy with the modal chromosomal number 64-97.

PMID- 12516396
TI  - [A case of diffuse panbronchiolitis].

PMID- 12516397
TI  - [Potential anxiolytic role of c-fos antisense oligonucleotide in social-defeated
      rats].
AB  - OBJECTIVES: This study was to explore the therapeutic potential of c-fos
      antisense phosphorothioate oligonucleotide and the possible molecular mechanism.
      METHODS: On the basis of the sequence of c-fos mRNA, two 15-mer phosphorothioated
      oligodeoxynucleotide(ODN) were synthesized. Antisense ODN was corresponded to the
      initiation codon of c-fos mRNA. The complementary sense and vehicle(saline)
      served as controls. Anxiety was induced in rats by a social-defeated paradigm and
      then rats were given a 5-minute exposure to the plus maze and open field test.
      Rats were injected c-fos antisense, sense ODNs and vehicles into the lateral
      ventricle through stainless-steel guide cannulate implanted unilaterally from the
      beginning of the experiment. The expression of the protein product of the
      immediate early gene c-fos was analyzed with immunochemistry in different brain
      regions, such as the amygdala and paraventricularis hypothalami nucleus. Computer
      assisted image analysis was performed to quantify the results of immuno
      cytochemistry. RESULTS: Socially defeated c-fos antisense-treated rats displayed
      obviously reduced anxiety-related behavior, as they spent significantly more time
      in the open arms of the plus maze compared to sense ODN- and vehicle-treated
      rats. The behavioral effects were similar to those of established anti-anxiety
      drugs(diazepam). Antisense oligodeoxynucleotide significantly decreased Fos
      positive nucleus in paraventricularis hypothalami nucleus. The inhibitory
      efficiency was 57.03%. CONCLUSION: Our data provide further evidence that c-fos
      is involved in acute stress elicited anxiety related behavior.

PMID- 12516398
TI  - [Substitution of BMEC-CM for hematopoietic stimulators in the culture of CFU-GM
      and HPP-CFC].
AB  - The effects of > 10 kD component of serum-free conditioned medium from murine
      bone marrow-derived endothelial cell line on the formation of CFU-GM and HPP-CFC
      were investigated. We found that > 10 kD component alone could stimulate CFU-GM
      colony formation in dose-dependent. Above- 10 kD component supplemented with GM
      CSF not only resulted in significant increase of CFU-GM as compared with > 10 kD
      or GM-CSF alone, but also could stimulate HPP-CFC formation. The effect of > 10
      kD component on the formation of HPP-CFC was also in dose-dependent. The
      component above- 10 kD combined with IL-3, IL-6, EPO, SCF or GM-CSF further
      enhanced HPP-CFC colony formation. The results suggest that > 10 kD component may
      be used as the substitutes of hematopoietic growth factors to stimulate the
      formation of CFU-GM and HPP-CFC.

PMID- 12516399
TI  - [Effects of Nao-Yi-An granule on activity of cytochrome c oxidase in hippocampus
      of experimental intracerebral hemorrhagic rats].
AB  - OBJECTIVE: To explore the neuronal protective effects of a traditional Chinese
      medicine complex Nao-Yi-An granule(NYA) on experimental intracerebral
      hemorrhage(ICH) in rats. METHODS: Eighty collagenase-induced ICH rats were used.
      At 12 h, 24 h, 2 d, 4 d, 7 d, cytochrome c oxidase(CO) activity was measured with
      histochemistry combined with gray scale scanning. Pyramidal cell(PC) counting was
      also employed following Nissl's staining. RESULTS: The CO activities in NYA
      treated group were less than those in model control group, and the neuronal loss
      was less in NYA-treated group than that in model control group. CONCLUSIONS: The
      neuronal protective mechanism of NYA following ICH may be related with its
      maintaining activity of cytochrome c oxidase, which contributes to improving
      cellular aerobic metabolism and increasing energy supply for cells.

PMID- 12516400
TI  - [Expression of autoantibodies to ICA512 and GAD in the sera of patients with
      diabetic ketoacidosis or ketonemia].
AB  - To explore the expression of the autoantibodies to ICA512 and GAD65 in the sera
      of diabetic patients who will be diagnosed as Type 1 diabetes, autoantibody
      assays were carried out in 15 diabetic patients complicated with ketonemia or
      ketoacidosis and in 19 healthy controls. The results were that the positive
      ratios of these autoantibodies were higher in the patient's sera than in the
      control's, and were higher in patients with shorter disease duration than those
      with longer disease duration. It is suggested that detecting these autoantibodies
      is helpful to the classification of diabetes and the disease duration affects the
      antibody's positive ratio.

PMID- 12516401
TI  - [Primary study of HCV replication in HepG2 cells inoculated by anti-HCV positive
      and HCVRNA RT-PCR positive serum].
AB  - OBJECTIVE: To study HCV replication in HepG2 cell line and to establish a stable
      HepG2 cell line infected with HCV. METHODS: Continuous inoculation of anti-HVC
      positive and HCVRNA RT-PCR positive sera was used to infect HepG2 cells. The plus
      and minus strains of HCVRNA were detected by reverse transcription polymerase
      chain reaction in the HepG2 cells. Virus particles were observed in
      postinoculated HepG2 cells by transmission electron microscope.
      Immunohistochemical staining was used respectively to detect HCV antigen, HCVNS5
      and HVC capsid in postinoculated HepG2 cells. RESULTS: HCV RNAs (both plus and
      minus strains) were found from the first passage to the third passage of
      postinoculation HepG2 cells, and HCV viruslike particles were detected in the
      third passage of the infected HepG2 cells, those particles mostly occurred within
      cytoplasm, their diameters were between 30-60 nm, and gathering silver particles
      were found in immunogold silver staining of HCV NS5/capsid protein in infected
      HepG2 cells. Gathering gold particles were found mostly within vesicles in
      cytoplasm by immuno gold electron microscopy. CONCLUSION: HepG2 cell line
      infected by HCV is established by continuous inoculation of anti-HCV positive and
      HCVRNA positive sera. HCV can replicate and produce virus-like particles in HepG2
      cells, which may occur in the serial passages of post-infected HepG2 cells.

PMID- 12516402
TI  - [Impairment effect of diabetes mellitus combined with hypertension on artery
      vasodilation].
AB  - OBJECTIVES: This study was to assess the relationship between endothelial
      dysfunction, and to explore smooth muscle dysfunction and the synergic action of
      different risk factors on impairment of artery vasodilation. METHODS: Using high
      resolution ultrasound, the dilator response of the brachial artery to 500
      micrograms of sublingual nitroglycerin (NTG) was measured in patients with Type 2
      diabetes mellitus (Group 1), patients with hypertension (Group 2), patients with
      both Type 2 diabetes mellitus and hypertension (Group 3), and control subjects
      (Group 4). Blood pressure, total serum cholesterol, basic vessel size, and flow
      mediated endothelium-dependent dilation (EDD) were also measured. RESULTS: On
      multiple linear regression analysis, a reduced vasodilator response to NTG was
      positively correlative with reduced EDD(P < 0.001). EDD was reduced in Group 1 (P
      < 0.05), Group 2 (P < 0.01) and Group 3(P < 0.01) compared to Group 4, but only
      Group 3 showed significantly reduced dilator response to NTG(P < 0.00).
      CONCLUSION: The impairment of vasodilator response to exogenous NO is associated
      with reduced EDD. More risk factors may aggravate impairment of vasodilation.

PMID- 12516403
TI  - [99mTc-ECD SPECT CBF-quantification and its clinical significance].
AB  - OBJECTIVE: To establish a quantitative method of non-blood withdrawn with 99mTc
      ECD SPECT for measuring cerebral blood flow (CBF). METHOD: Combining three
      compartment models and technology of the best parameters by computer with 99mTc
      ECD SPECT to quantitate CBF and regional cerebral blood flow (rCBF) in control
      group and patient group. RESULTS: The CBFs of the control group (8 cases) and the
      patient group (16 cases) were (57.16 +/- 4.21) ml.min-1/100 g and (38.80 +/-
      8.21) ml.min-1/100 g, respectively. The CBF and rCBF were significantly lower in
      patient group than those in control group (P < 0.05). CONCLUSION: The method is
      simple and more convenient for quantification of CBF in patients with brain
      disorders, and it may increase the diagnostic sensitivity and the accuracy of
      focus location. It is suggested that the method is accurate and reliable.

PMID- 12516404
TI  - [Relationship between hot spot mutation in hepatitis B virus basic core promotor
      and HBeAg status].
AB  - OBJECTIVE: This paper was to study the influence of hot spot mutation in
      hepatitis B virus (HBV) basic core promotor (BCP) (nt1762 and nt1764) on HBeAg
      status of asymptomatic HBV carriers. METHODS: Mismatched PCR was used to amplify
      the fragment of HBVBCP and the fragments were analysed by restrict enzyme assay.
      Ninety cases of HBV infection were tested for hot spot mutations in HBVBCP.
      RESULTS: Twenty-six (43.3%) of 60 asymptomatic HBV carriers with HBeAg negative
      were found to have hot spot mutations in HBVBCP, among which 20 cases were
      accompanied by the mutation of nt 1896 in HBV Pre-C region. Hot-spot mutation in
      HBVBCP, however, occurred only in 3(10%) of 30 asymptomatic HBV carriers with
      HBeAg positive. For further investigation the HBVBCP hot spot mutations in
      asymptomatic HBV carriers without mutation of HBV Pre-C region were studied.
      Six(31.6%) of 19 asymptomatic HBV carriers with HBeAg negative were found to have
      hot spot mutation in HBVBCP. Two(7.1%) of 28 asymptomatic HBV carriers with HBeAg
      positive had hot spot mutations in HBVBCP, and there was a statistically
      significant difference between two groups. CONCLUSIONS: Hot spot mutations in
      HBVBCP is common in the HBV carriers with HBeAg negative and usually accompanies
      with nt1896 mutation of HBV Pre-C region. It is possible that Hot spot mutation
      in HBVBCP is a new reason of HBeAg negative HBV infection.

PMID- 12516405
TI  - [The relationship between clinical prognosis and classification of the isoforms
      of fuse gene in acute promyelocytic leukemia].
AB  - To check the anti-apoptosis gene bcl-2 protein/mRNA expression in 28 acute
      promyelocytic leukemia (APL), by immunohistochemistry and in situ hybridization,
      and to analyse the relationship among the bcl-2 gene expressions, clinical
      prognosis and classification of the isoforms of fuse gene in APL. The result
      shows the two types of isoforms of PML-RAR alpha have no significance in bcl-2
      protein/mRNA expression, indexes of clinical prognosis. This shows that the
      classification of PML-RAR alpha isoform has no influence on clinical prognosis.

PMID- 12516406
TI  - [Treatment of lymphoma and malignant melanoma with autologous peripheral blood
      stem cell transplantation].

PMID- 12516407
TI  - [Distribution of bacteria and analysis of their sensibility to antibiotics in
      patients with hospital-acquired pneumonia].
AB  - OBJECTIVES: This study was explore the distribution of the bacteria and their
      sensibility to antibiotics in hospital-acquired pneumonia. METHODS: One hundred
      and ninety-six bacterium species were collected in patients with the hospital
      acquired pneumonia to make sputum culture. The sensibility of the bacteria to
      antibiotics were examined by KB paper method and the minimal-inhibitory
      concentration by gel double multiple dilute method. RESULTS: Most of the G-
      bacteria were pseudomonas aeruginosa (30%) and klebsiella bacillus (22%). Most of
      the G+ bacteria were staphylococcus epidermidis (14%) and staphylococcus aureus
      (12%). G- bacteria were sensitive to impienem(98%), cefoperazone(90%),
      ceftriaxone(90%), leftazidime(92%), ciprofloxacin(90%), and amikacin(89%). The
      sensibility of vancomycin to G+ bacteria was 100%. CONCLUSIONS: The pseudomonas
      aeruginosa, klebsiella bacillus, staphylococcus epidermidis, and staphylococcus
      aureus are the most important bacteria in patients with hospital-acquired
      pneumonia. Imipenem, cefoperazone, ceftriazone, leftazidime, ciprofloxacin,
      amikacin, and vancomycin are effective antibiotics for treating hospital-acquired
      pneumonia.

PMID- 12516408
TI  - [Influence of IFN-alpha and IFN-alpha combined with GM-CSF on expression of the
      genes related to cell apoptosis of MNCs from bone marrow in CML patients].
AB  - OBJECTIVE: To investigate the effects of interferon-alpha(IFN-alpha) and IFN
      alpha combined with granulocytic macrophage colony-stimulating factor(GM-CSF) on
      expression of bcr-abl, bcl-2 and c-myc genes in the mononuclear cells(MNCs) from
      bone marrow(BM) of the patients with chronic myelogenous leukemia at chronic
      phase(CML-CP). METHODS: The MNCs were collected from bone marrow of 14 CML-CP
      patients by centrifugalization in lymphocyte-separation medium, and cultivated in
      the medium with IFN-alpha and IFN-alpha plus GM-CSF for 24 hours. The expression
      levels of bcr-abl, bcl-2, c-myc and beta-actin were detected by using relatively
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and optical
      density scanning technology for the amplified fragments. The statistical
      differences between each inducing experimental group and the control were
      analyzed by t-test in pairs. RESULTS: Both IFN-alpha (200 U.ml-1) and IFN-alpha
      combined with GM-CSF (10 ng.ml-1) significantly inhibited bcr-abl gene
      expression, meanwhile IFN-alpha partially suppressed c-myc and bcl-2 gene
      expression, and GM-CSF significantly inhibited bcl-2 gene expression but
      partially upregulated bcr-abl and c-myc gene expression levels on the basis of
      IFN-alpha effects. CONCLUSIONS: Both IFN-alpha and IFN-alpha plus GM-CSF can
      inhibit the expression of anti-apoptosis gene such as bcr-abl and bcl-2, and
      regulate the expression of c-myc. It is the possible mechanism of IFN-alpha
      therapy or combined therapy on CML at chronic phase that the malignant clone
      expansion is inhibited by promoting apoptotic cell death.

PMID- 12516409
TI  - [Comparison of infectious brain edema models induced by different kinds of
      pertussis bacilli in rats].
AB  - OBJECTIVE: To understand the difference of infectious brain edema models induced
      by varied kinds of pertussis bacilli in rats and to look for a new infectious
      brain edema model. METHODS: Sprague-Dawley rats were randomly divided into 3
      groups: normal saline group(NS); rude pertussis bacilli(PBR); purified pertussis
      bacilli(PBP). After infectious brain edema model was induced by rude pertussis
      bacilli or purified pertussis bacilli, the water content(WC), Evan's blue
      content(EB), Na+ and K+ content in brain tissues were measured. RESULTS: The WC,
      EB and Na+ contents in brain tissues in PBR and PBP groups were significantly
      increased than those in NS group; K+ content was significantly decreased in PBR
      and PBP groups than that in NS group(P < 0.01). Evan's blue discoloration was
      demonstrated in all rats of PBR group, but 6 rats of PBP group showed bluish
      discoloration. EB content in brain tissues was significantly increased in PBR
      group than that in PBP group. CONCLUSIONS: The infectious brain edema model can
      be induced by rude pertussis bacilli or purified pertussis bacilli in rats, the
      former gives priority to mixed brain edema, and the latter mainly avails
      cytotoxin brain edema.

PMID- 12516410
TI  - [The efficacy of the native flumazenil for acute poisoning with benzodiazepines].
AB  - OBJECTIVE: To evaluate the efficacy of the native flumazenil for acute self
      poisoning with benzodiazepines. METHODS: One hundred and twenty-six patients with
      unconsciousness from benzodiazepines-induced self-poisoning were randomly divided
      into two groups: flumazenil group(Group II, 63 cases) were treated with
      flumazenil, and conventional-medicine group(Group I, 63 cases) with
      placebo(glucose, vitamin C, KCl). A modified Glasgow Coma Scale(MGCS) and
      Observer's Assessment of Alertness/Sedation Scale(OAA/S) were used in the
      assessment of consciousness. RESULTS: MGCS were increased by 5.3, 8.0, 9.4 and
      7.3 at 15 min, 30 min, 60 min and 180 min after intravenous flumazenil(P < 0.01)
      and by 5.2, 7.7, 8.7 and 6.9 in comparison with conventional-medicine group(P <
      0.01). OAA/S increased by 1.9 compared with conventional-medicine group(P <
      0.01). No severe side-effects were found in the treatment. CONCLUSIONS:
      Flumazenil might improve benzodiazepines-induced unconsciousness markedly and may
      be the most effective antagonist of benzodiazepines.

PMID- 12516411
TI  - [A case of primary larynx non-Hodgkin's disease].

PMID- 12516412
TI  - [Effects of retinoic acid on proliferation and differentiation of human lung
      squamous carcinoma cell line].
AB  - Human lung squamous carcinoma cell line(TUL cell) was treated with 5 x 10(-6)
      mol.L-1 all-trans retinoic acid(ATRA). Cell numbers were estimated by 0.4% trypon
      blue stain. MTT test was used for determining the percentage of cell growth
      inhibition(GI). DNA syntheses of cells were evaluated by 3H-thymidine
      incorporation. Cell ultrastructure was examined by transmission electron
      microscope(TEM). TUL cells were treated with or without ATRA, and transplanted in
      cutaneous of Balb/c nude mice. The results showed that: 1. The speed of cell
      growth in study group was smaller than that in control group. 2. The GI of cell
      lines TUL was 42.3%. 3. The percentage of 3H-thymidine incorporation of TUL cells
      was declined significantly. 4. Ultrastructure under TME showed that TUL cells
      treated with ATRA was suppressed. These results suggest that ATRA has the effects
      on growth-inhibition and differentiation-induction of TUL cell.

PMID- 12516413
TI  - [Myocardial injury in non-cardiogenic disease operation].

PMID- 12516414
TI  - [Effect of indomethacin on natural killer(NK) cell and T lymphocyte subsets from
      patients with hepatocellular carcinoma].
AB  - Twenty-one patients with advanced hepatocellular carcinoma were randomly divided
      into two groups. They were orally given tegafur 200 mg three times a day
      with(Group I, n = 11) or without(Group II, n = 10) indomethacin 25 mg three times
      a day for 7 days. Before and after the therapies the NK cell and T-lymphocyte
      subset activity in peripheral blood were measured. The results showed that NK
      cell activity in Group I was significantly higher than that in Group II(P < 0.01)
      and that before the treatment as well(P < 0.05). T-lymphocyte subsets had no
      significant difference between the two groups and before or after the therapy. It
      is suggested that the indomethacin might improve the NK activity of the patients
      with advanced hepatocellular carcinoma.

PMID- 12516415
TI  - [Preparation and qualitative control of compound Dyclonine's suspending mixture].
AB  - The paper deals with the composition, preparation and qualitative control of
      compound Dyclonine's suspending mixture, one of gastroscopic mucomembranous
      anesthetics. The content of Dyclonine hydrochloride was detected by ultraviolet
      spectrophotometry. It shows that the average rate of recovery is 100.80%, RSD =
      1.32%(n = 6). At room temperature, the appearance and content of the preparation
      are not changed in 0, 30, 180, 365 days respectively. The preparation is widely
      and successfully used in clinics with easy procedure and excellent stability.

PMID- 12516416
TI  - [A comparative study of GRA1 gene between the two strains of different virulence
      of Toxoplasma gondii].

PMID- 12516417
TI  - [Preliminary study on transmission of transfusion-transmitted virus infection by
      sexual contact].

PMID- 12516418
TI  - [The expression of P-170 and chromosomal abnormality in refractory/relapse acute
      leukemia].

PMID- 12516419
TI  - [A case of giant cervix fibromyoma].

PMID- 12516420
TI  - [Expression of cathepsin D and its significance in the benign and malignant
      lesions of stomach].

PMID- 12516421
TI  - [Effects of sera of patients with pregnancy-induced hypertension on the synthesis
      of nitric oxide and endothelin-1 of endothelial cells].

PMID- 12516422
TI  - [Determination of rutin in bud of Sophora japonical by high performance liquid
      chromatography].

PMID- 12516423
TI  - [Diagnosis of human bladder cancer by detecting the telomerase activity in
      exfoliated urothelial cells].

PMID- 12516424
TI  - [Peripheral lymphocyte apoptosis induced by lipopolysaccharide].

PMID- 12516425
TI  - [Relation between the protein loss and small solates transport on peritoneal
      dialysis].

PMID- 12516426
TI  - [Clinic observation of the effect on prevention of caries by using pit and
      fissure sealants].

PMID- 12516427
TI  - [Experimental study on Schwann cells cytoplasmic neurotrophic proteins to improve
      the regeneration of the injured peripheral nerve in vivo].
AB  - OBJECTIVE: To study the effects of Schwann cell cytoplasmic derived neurotrophic
      proteins (SDNF) on the regeneration of peripheral nerve in vivo. METHODS: Ninety
      adult SD rats were chosen as the experimental model of degenerated muscle graft
      with vascular implantation bridging the 10 mm length of right sciatic nerve. They
      were divided randomly into three groups, 30 SD rats in each groups. 25
      microliters of 26 ku SDNF (50 micrograms/ml, group A), 58 ku SDNF (50
      micrograms/ml, group B) and normal saline(group C) were injected respectively
      into the proximal, middle and distal part of the degenerated muscle grafts at
      operation, 7 and 14 days postoperatively. The motorial function recovery
      assessment was carried out every 15 days with the sciatic nerve function
      index(SFI) after 15 days to 6 months of operation. Histological and
      electrophysiological examination of regenerating nerve were made at 1, 3 and 6
      months postoperatively. RESULTS: There were significant statistic differences
      between the both of experimental groups(group A and B) and control group(group C)
      in the respects of the histological, electrophysiological examination and SFI(P <
      0.01). CONCLUSION: The 26 ku SDNF and 58 ku SNDF can improve the regeneration of
      the injured peripheral nerve in vivo.

PMID- 12516428
TI  - [Neurobiological effect of nerve regeneration conditioned fluid on motoneuron].
AB  - OBJECTIVE: To explore the mechanism of tissue specificity of neurotropism in
      peripheral nerve regeneration, we investigated the biological characteristics of
      the nerve regeneration conditioned fluids(NRCF) on motoneuron of SD rats cultured
      in vitro. METHODS: Silicon chambers were sutured respectively to the distal
      stumps of motorial branch of femoral nerve and saphenous nerve to collect NRCF,
      namely MD-NRCF and SD-NRCF. The rats cortex motoneuron were divided into 4 groups
      and cocultured with MD-NRCF, SD-NRCF, b-FGF and serum-free medium respectively.
      The cultured cells were photoed under phase-contrast microscope, their longest
      neurites and cell-body areas were measured by cell image processing computer
      system. MTT automated colorimetric microassay was also adopted to quantify the
      activation of cultured motoneurons in each group. RESULTS: Cells of MD-NRCF group
      had longer neurites than those of the other three groups, and their activation
      was also superior to those of the other groups. CONCLUSION: The results suggest
      that MD-NRCF has more significantly neurite-promoting and neurobiological effects
      on motoneuron than SD-NRCF and b-FGF.

PMID- 12516429
TI  - [Effect of electroacupuncture on mRNA expression of NGF and IGF-1 in injured
      nerve].
AB  - OBJECTIVE: To investigate the effect of electroacupuncture on mRNA expression of
      NGF and IGF-1 in injured nerve. METHODS: Sciatic nerve injury model was
      established by transection of right side sciatic nerve in 90 male SD rats, which
      were randomly divided into two groups. The experimental group was treated with
      electroacupuncture, no treatment in the control group. The distal part of the
      injured nerve was harvested after 1, 2, 4, 6 and 10 weeks of operation and stored
      in the liquid nitrogen. The total RNA was extracted by the TRIzol reagent.
      Reverse transcriptase-polymerase chain reaction(RT-PCR) was used to detected the
      mRNA expression of NGF and IGF-1. RESULTS: The mRNA expression of NGF in the
      experimental group was increased quickly from the second week, and reached to
      highest level in the fourth week. It was much higher than that of the control
      group (P < 0.05). Then it began to decline in following time and approximately
      reached to the level of the first week after 10 weeks of operation. The mRNA
      expression of IGF-1 in the experimental group was remarkably increased in the
      second and fourth week, and which was much higher than that of the control group
      respectively(P < 0.05). Although the mRNA expression of IGF-1 after 10 weeks of
      operation in the experimental group was higher than that of the control group,
      but there was no significant difference between the two groups(P > 0.05). There
      was linear correlation in the fourth week between mRNA expression of NGF and IGF
      1 in the experimental group. CONCLUSION: The mRNA expression of NGF and IGF-1 can
      be elevated in injured nerve at early stage interfered with electroacupuncture.

PMID- 12516430
TI  - [Functional evaluation of electrical-injury nerve using somatosensory evoked
      potential technique].
AB  - OBJECTIVE: To investigate the characteristics and the pathologic classification
      of electrical-injury nerve using somatosensory evoked potential(SEP) technique.
      METHODS: SEP were detected and evaluated in 12 cases with electrical-injury nerve
      during operation, electrical stimulation was commenced from distal side of nerve
      where the structure of nerve looks normal under operating microscope, up to
      proximal side until evoking out a stable SEP predeterminate virtual value.
      Pathological examination and the following functional evaluation were compared
      with the values of SEP. RESULTS: At the site of nerve looking normal under
      operating microscope, perineurium appears normal or slightly thicken. But there
      are obvious fibrosis and fibrotic proliferation between fascicular and
      intrafascicular. Vessel plexus is not seen. At SEP stabilizely evoked site,
      nervous construction is normal, there are visible interfascicular vessel plexus
      and connective tissue appears loose. Comparing SEP values with pathological
      section, amplitude and latency of SEP is positively correlative with the quality
      of nerve. Eight cases repaired with SEP technique to select the anastomosis site
      for nerve transplantation were followed up, two-point discrimination reached
      grade III (America hand surgery association criterion) within 62.5% cases.
      CONCLUSION: SEP technique is valuable method for functional evaluation of
      electrical- injury nerve which has a complicated pathology. The pathology of
      electrical-injury nerve can be classified into 4 types, type A: fibrosis of
      nerve; type B: nerve looking normal under operation microscope, perineurium
      appears thicken, and there are obvious fibrosis and fibrotic proliferation
      between fascicular and intrafascicular, vessel plexus is rarely to see; type C:
      nerve looks normal, lymphocyte infiltration exists and it is obvious that there
      are many physalis-like, retrogressive construction in the section; type D:
      nervous construction is normal, there are visible interfascicular vessel plexus,
      and connective tissue appears loose, SEP always can be stably evoked.

PMID- 12516431
TI  - [Experimental study of pathophysiological changes for peripheral nerve after
      neurolysis].
AB  - OBJECTIVE: To investigate the changes of regeneration and conduction function for
      peripheral nerve after neurolysis by nerve special staining and
      electrophysiology. METHODS: Sixty Sprague-Dawley male rats were randomly divided
      into four groups(n = 15), four methods were designed on rats models of sciatic
      nerve compression. There were simple decompression as group A, internal
      neurolysis after decompression as group B, lemithason(0.5 mg/kg) injected in the
      epineurium after decompression as group C, and lemithason(0.5 mg/kg) injected
      around the epineurium after decompression and internal neurolysis as group D.
      Motor nerve conduction velocity(MNCV) and motor latency (Lan) were monitored at
      1,2,3,4,5 weeks after decompression, sections were regularly taken from the
      previously compressed area to perform morphometric analysis. RESULTS: After 2
      weeks of decompression, the significant recovery were observed in both MNCV and
      Lan of four groups. Up to the 5th week of decompression, recovery of
      electrophysiology was significantly faster in group C and D than that of group A
      and B, particular in group C(P < 0.05), while group A compared with group B,
      there was no statistical difference in both MNCV and Lan(P > 0.05). Morphometric
      analysis showed that a lot of neural regeneration fibers were observed in group C
      and D after 3 weeks of decompression. CONCLUSION: Decompression can improve nerve
      conduction function significantly, while injection of lemithason in epineurium
      after decompression can promote the structure and function recovery of injured
      nerve.

PMID- 12516432
TI  - [Experimental studies on rabbit facial nerve regeneration in chitin tubes
      containing nerve growth factor].
AB  - OBJECTIVE: To evaluate the nerve regeneration after implantation of chitin tubes
      containing nerve growth factor(NGF) in the rabbit facial nerve. METHODS:
      Bilateral 8 mm defect of superior buccal divisions of the facial nerves were made
      in 16 New Zealand rabbits. Chitin tubes containing NGF were implanted into the
      gaps, and autologous nerves were implanted into the right gaps as control. The
      nerve regeneration was evaluated with electrophysiological and ultrastructural
      examination after 8 and 16 weeks of operation. RESULTS: Chitin tubes containing
      NGF successfully induced the nerve regeneration, regularly arranged myelinated
      and unmyelinated axons could be observed across the 8 mm gaps, and the myelin
      sheath was thick with clear lamellar structure at 8 weeks after operation, The
      regenerated nerve fibers increased and were more mature at 16 weeks after
      operation. There were no significant difference in electrical impulse conduction
      velocity through the neural regeneration between the experimental and control
      sides (P > 0.05). CONCLUSION: Chitin tubes containing NGF can provide optimal
      conditions for regeneration of rabbit facial nerve.

PMID- 12516433
TI  - [Protective effect of tumor necrosis factor-alpha on motor neurons after
      peripheral nerve injury].
AB  - OBJECTIVE: To investigate the protective effect of tumor necrosis factor
      alpha(TNF-alpha) on spinal motor neurons after peripheral nerve injury. METHODS:
      Twenty Wistar rats were divided into two groups, the right sciatic nerves of 20
      Wistar rats were transected, the proximal stumps were inserted into a single
      blind silicone tube. 16 microliters of normal saline(NS) and TNF-alpha(30 U/ml)
      were injected into the silicone tubes. After 2 weeks, the 4th, 5th lumbar spinal
      cord were taken for examination. Enzyme histochemical technique and image
      analysis were used to show acetylcholinesterase(AChE) and nitric oxide
      synthase(NOS) activity of spinal motor neurons. RESULTS: The number of AChE and
      NOS staining neurons were 8.65 +/- 1.98 and 5.92 +/- 1.36 in the experimental
      group and 6.37 +/- 1.42 and 8.67 +/- 1.45 in the control group respectively,
      there were significant difference between the two groups(P < 0.01). CONCLUSION:
      It suggests that TNF-alpha has protective effect on motor neurons after
      peripheral nerve injury.

PMID- 12516434
TI  - [Reconstruction of the shoulder joint function in the older obstetrical palsy].
AB  - OBJECTIVE: To study the reconstructional method and effect of shoulder joint
      function in the older obstetrical palsy with medial rotation contracture
      deformity. METHODS: From April 1996 to July 1999, 7 patients of older obstetrical
      palsy were adopted in this study. Among them, there were 5 males and 2 females,
      aged from 13 to 21 years old. No previous operation history and the main
      deformity was medial rotation contracture of shoulder. During operation, these
      patients were treated with "Z"-shape elongation of the tendon of subscapular
      muscle, transfer of the tendons of latissimus dorsi and teres major muscle to the
      tendons of supraspinous and infraspinous muscles. RESULTS: Followed up for 6 to
      44 months(averaged 19 months), the Gilbert grading and Mallet scoring were 1.57,
      7.57 preoperatively versus 3.45, 10.86 postoperatively, the abduction and
      external rotation of the shoulder joints recovered obviously. CONCLUSION: It is
      an effective operation for the older obstetrical palsy with medial rotation
      contracture of shoulder.

PMID- 12516435
TI  - [Functional assess for reconstruction of tendon in finger amputation].
AB  - OBJECTIVE: To evaluate the function of injured hand after repair of finger stump
      and reconstruction of digit tendon attachment in finger amputation. METHODS: From
      1992 to 1998, 20 cases with amputation of the 2nd to the 5th fingers were
      investigated, of which reconstruction of digit tendon attachment in 10 cases
      (group A) and routine operation without reconstruction of digit tendon attachment
      in other 10 cases (group B). After 6 months of operation, the tension test,
      fatigue test the sense of stability in motion and the perimeter of forearm in
      injured hand and the corresponding healthy hand were compared. RESULTS: The
      differences were remarkable (P < 0.01) between group A and group B in the tension
      test of injured finger, the fatigue test, the sense of stability in motion and
      the perimeter of injured arm. CONCLUSION: The digit of injured finger should be
      reconstructed in finger amputation in order to furthest maintain the function of
      injured hand.

PMID- 12516436
TI  - [Clinical application of the medial fasciocutaneous flap of arm].
AB  - OBJECTIVE: To study the clinical application of the medial arm fasciocutaneous
      flap based on the medial septocutaneous branches of the brachial vessel. METHODS:
      Since 1994, the medial arm fasciocutaneous flap based on the medial
      septocutaneous branches of the branchial vessel has been used to cure scar
      contracture of axillary and elbow joint, radiated ulcer of the chest wall.
      Eighteen clinical cases were reported. Among them, there were 14 males and 4
      females, aged from 6 to 48 years old. The flaps, of which 3 were proximally based
      and 15 distally based, were designed 23 cm x 11 cm as maximal size and 10 cm x 6
      cm as minimal size. RESULTS: All the flaps survived and the excellent function
      and cosmetic result were achieved. CONCLUSION: The medial arm fasciocutaneous
      flap is thin, soft and relatively hairless, so it is suitable for repairing the
      soft tissue defect of the axillary or elbow joint. There are consistently present
      perforators at both ends that allow one to rotate long flaps around pivoting
      points immediate to the areas needing coverage. Moreover, this flap is
      characterized by the simplicity of the surgical techniques and circulatory
      reliability.

PMID- 12516437
TI  - [Repairing of soft tissue defect in leg by free vascularized thoracoumbilical
      flap with reversed flow].
AB  - OBJECTIVE: To investigate the clinical effect of free vascularized
      thoracoumbilical flap with reversal flow in repairing the soft tissue defect in
      leg with tibia exposure. METHODS: Forty-four casting mould specimens of leg
      arteries were studied firstly. Then 25 cases with soft tissue defect and tibia
      exposure in the proximal-middle segment of leg were adopted in this study. Among
      them, 18 cases had long distance thrombosis of the anterior tibial vessels or
      posterior tibial vessels due to traumatic lesion. The maximal size of defect was
      28 cm x 11 cm and the minimal size of defect was 11 cm x 9 cm. In operation, the
      thoracoumbilical flap which was based on the inferior epigastric vessels was
      anastomosed to the distal end of the anterior tibial vessels or posterior tibial
      vessels. RESULTS: Anterior tibial artery, posterior tibial artery and fibular
      artery had rich communication branches in foot and ankle. All the flaps survived,
      the color and cosmetic result of them were good. CONCLUSION: The free
      vascularized thoracoumbilical flap with reversed flow is practical in repairing
      the soft tissue defect of leg with tibia exposure. Either the anterior tibial
      vessels or the posterior tibial vessels is normal, and the distal end of injured
      blood vessels is available, this technique can be adopted.

PMID- 12516438
TI  - [The effect of soft tissue repairing at different times on the union of type III
      b tibial fracture].
AB  - OBJECTIVE: To investigate the effect of soft tissue repairing at different times
      on the union of type III b tibial fracture. METHODS: From January 1987 to January
      1999, seventy-six type III b tibial fractures were divided into 3 groups: early
      group(0 to 7 days), subacute group(8 to 30 days), late group(more than 30 days)
      according to the time of soft tissue repairing. The morbidity rates of
      complications such as infection, nonunion as well as the time to union were
      compared respectively. RESULTS: Followed up for 10 to 36 months (averaged 24
      months), the infection and nonunion rates of early group were lower than that of
      subacute and late groups(P < 0.01), the average time of fracture union of early
      group was less than that of subacute and late groups. CONCLUSION: Early soft
      tissue repairing can decrease the complications and the time to union of Type III
      b tibial fracture obviously. The time of "early" should be limited in one week
      and as soon as possible.

PMID- 12516439
TI  - [Therapeutic effect of liposome on II degree burn wound].
AB  - OBJECTIVE: To study the therapeutic effect of Suyuping in which liposome is the
      main constituent on II degree burn wound. METHODS: From October 1998 to October
      1999, 42 cases with II degree burn wound were adopted in this study. Among them,
      there were 30 males and 12 females, the average wound area was (23.4 +/- 9.7)%.
      The wounds on the left side of body were managed with sulfadiazine argentum(SD
      Ag) while that on the right side with Suyuping. Healing and other situation about
      the burn wounds were observed and recorded at times. RESULTS: Forty-two patients
      completely healed when discharged from hospital. The average wound area managed
      with Suyuping was (11.2 +/- 7.3)% and the area with SD-Ag was (9.4 +/- 5.8)%. The
      mean healing time of Suyuping group was(18.4 +/- 4.7) days while that of SD-Ag
      was (23.5 +/- 7.9) days, there was significant difference(P < 0.05). Suyuping
      group presented few wound pain, allergy, bleeding and the side effect was less.
      CONCLUSION: Suyuping can accelerate wound healing and attenuate wound pain,
      allergy and bleeding, it is a potential and specific topical agent for treating
      II degree burn wound.

PMID- 12516440
TI  - [Repairing of inguinal scar contracture deformity in children with
      transpositional fasciocutaneous flap].
AB  - OBJECTIVE: To investigate the repairing method of inguinal scar contracture
      deformity in children with transpositional fasciocutaneous flap of anterior
      medial side of thigh. METHODS: From August 1989 to August 1999, 33 cases with
      inguinal scar contracture deformity were adopted in this study. Among them, there
      were 26 males and 7 females, aged from 3 to 11 years old. The transpositional
      fasciocutaneous flap consisted of a huge tongue-shape flap with a pedicled
      triangular flap between the edge of skin defect and the above tongue-shape flap.
      The maximal size of the transpositional fasciocutaneous flap was 18 cm x 10 cm
      and the minimal size was 13 cm x 8 cm, the transpositional angle was 60 degrees
      to 80 degrees. During operation, the tongue-shape flap was used to repair the
      inguinal region and the triangular flap was used to repair the donor site in one
      stage. RESULTS: All the flaps survived. The function and appearance of perineum
      were satisfactory. CONCLUSION: The transpositional fasciocutaneous flap is
      suitable for repairing the inguinal scar contracture deformity in children, and
      skin graft is unnecessary.

PMID- 12516441
TI  - [Treatment of huge hemangioma with intervention-embolism and circumferential
      suture maneuver].
AB  - OBJECTIVE: To demonstrate the effectiveness of operative resection for patients
      with huge hemangioma. METHODS: Eight cases were adopted in this study, including
      5 males and 3 females. Among them, 5 cases with hemangioma on the face and neck,
      1 case on the back, 1 case on the buttock, and 1 case on the leg. The maximal
      size of the hemangioma was 31.2 cm x 9.1 cm and the minimal size was 27.3 cm x
      6.0 cm. Before operation, angiography was taken to find out the size of tumor.
      During operation, intervention-embolism and circumferential suture were carried
      out to control bleeding so that resection of tumor was practicable. RESULTS:
      There had been successful result in all the cases with huge hemangioma. No
      recurrence were found with following up 8 months to 4 years(averaged 13 months).
      CONCLUSION: Angiography of the hemangioma is important in providing the
      informations for the operation design. The intervention-embolism and
      circumferential suture can control and reduce the bleeding in operation. Combine
      of these techniques is essential for the treatment of huge hemangioma.

PMID- 12516442
TI  - [Huge thoracic wall defect repaired by tissue engineered bone transplantation].
AB  - OBJECTIVE: A rare huge desmoplastic fibroma on thoracic wall in 1 female case of
      25 years old was resected, and the accompanying huge thoracic wall defect, ribs
      and soft tissues were repaired by tissue engineered bone and pedicled flap. The
      paper aims to explore the clinical results of early stage after operation.
      METHODS: Autogeneic bone marrow stromal cells (MSC) were obtained from bone
      marrow puncture of iliac bone and isolated and cultured according to the
      Houghton's methods, MSC were directively induced and differentiated to
      osteoblasts. Allogeneic ribs were made to the bio-derived bone scaffold materials
      after treatment of decell, deantigen, decalcification and dry freezing. 5 x
      10(6)/ml MSC were cocultured with the bio-derived bone for 6 days in vitro. After
      intact resection of tumor, the diaphragm flap was applied to repair pleural
      cavity, the three defect ribs were repaired by tissue engineered bone and the
      soft tissue defect was repaired by transfer of pedicled ipsilateral abdominal
      flaps. RESULTS: The patient recovered well with first intention. Followed up for
      3 months, tissue engineered ribs were matured in vitro and the heart and
      pulmonary functions were improved markedly. CONCLUSION: The tissue engineered
      bone constructed by autogeneic MSC is advantageous in individual treatment.

PMID- 12516443
TI  - [Advance in study of artificial nerve].
AB  - OBJECTIVE: To review the advance in materials of nerve conduit and Schwann cell
      transplantation for preparation of artificial nerve with tissue engineering
      technique. METHODS: Recent literatures about artificial nerve, nerve conduit and
      Schwann cell transplantation were extensively reviewed. RESULTS: Many
      biomaterials such as silicon, dacron, expanded polytetrafluoroethylene(ePTFE),
      polyester and chitin could be used as nerve conduits to repair nerve defect, the
      degradable biomaterials were better. The nerve conduit with intrinsic filaments
      could be used to bridge an extended gap in peripheral nerve. Purified and
      cultured Schwann cells were still bioactive. Axonal regeneration could be
      enhanced after implantation of Schwann cells into nerve conduit. CONCLUSION: The
      ideal artificial nerve is composed of three dimensional biodegradable nerve
      conduit and bioactive Schwann cells, Schwann cells can be distributed in nerve
      conduit just like Bunger's band.

PMID- 12516444
TI  - [Biological characteristics of continuously subcultured human embryonic skeletal
      myoblasts].
AB  - OBJECTIVE: To investigate the biological characteristics of continuously
      subcultured human embryonic skeletal myoblasts, and choose the optimal seeding
      cells for muscle tissue engineering. METHODS: Human embryonic skeletal myoblasts
      were subcultured in vitro. The growth curve, rate of myotube formation(RMF) were
      used to evaluate the proliferative and differentiation ability of myoblasts, and
      to investigate the influence of fibroblasts contamination on myoblasts. RESULTS:
      The beginning 6 passages of myoblasts showed strong proliferative and
      differentiation ability. From the 8th to 20th passage, the rate of fibroblasts
      contamination was increased, it mainly showed the growth characteristics of
      fibroblasts with increased proliferation and low differentiation. After
      subcultured to the 20th passage, the degeneration of myoblasts was obvious.
      CONCLUSION: The myoblasts within 6 passages should be used as the seeding cells
      of muscle tissue engineering because of strong proliferative ability and high
      rate of myotube formation.

PMID- 12516445
TI  - [Osteoarticular allografts for repairing large bone or osteoarticular defects].
AB  - OBJECTIVE: To evaluate clinical outcome of bone or osteoarticular allografts.
      METHODS: From September 1991 to November 1997, large bone or osteoarticular
      defects secondary to bone tumors resection in 36 patients and severe trauma in 2
      patients were repaired by deep frozen or lyophilized allogeneic osteoarticular or
      diaphysis graft. RESULTS: No obvious immune rejection to the grafts was observed
      in most of the patients in early stage after operation. The patients were
      followed up from 1 year and five months to 7 years and five months with an
      average of 4.2 years. Limb function was satisfactory in 74.19% of the 31 survival
      patients with large osteoarticular or diaphysis allografts. CONCLUSION:
      Cryopreserved or lyophilized allogeneic osteoarticular grafts with decreased
      antigenicity and good biocompatibility are suitable materials for repairing large
      bone or osteoarticular defects.

PMID- 12516446
TI  - [Consideration on the problem of "ascension of the case poisoned by Chinese
      Traditional Medicines"].
AB  - OBJECTIVE: Desserting toxicity and reasonable usage of Chinese traditional
      medicines. METHODS: Analysing the understanding of toxicity of Chinese
      traditional medicines in Chinese medicine and pharmacology and the reason for
      ascension of the case poisoned by Chinese traditional medicines. RESULTS AND
      CONCLUSION: All medicines are poisonous. The venomous drug can cure disease when
      it is reasonably applied. On the contrary, the good medicine will be harmful to
      one's health if it is unreasonably used. In order to use Chinese traditional
      medicines securely and effectively, it is necessary to learn seriously theories
      of traditional Chinese medicine and pharmacology and experiences of using drugs
      and to strengthen the study on evaluation of security of Chinese traditional
      medicines.

PMID- 12516447
TI  - [Triterpenoid compounds of Prunella genus and their features of 13C NMR
      spectroscopy].
AB  - OBJECTIVE: To summarize the research advances and 13C NMR features of
      triterpenoid compounds in the plant of Prunella genus. METHODS: Consulting
      related literatures and summing up the triterpenoid compounds and their features
      of 13C NMR spectra. RESULT AND CONCLUSION: Up to now, 28 triterpenoid compounds
      were isolated from the plant of P. genus. of which 20 were in free state and 8
      were triterpenoid saponins. The 13C NMR spectra of different triterpenoids showed
      different features in respects such as skeletons, substituent groups and
      positions.

PMID- 12516448
TI  - [Advances in the research on pharmacological actions of flavone compounds].

PMID- 12516449
TI  - [Studies on single cell cloning of Ginkgo biloba L].
AB  - OBJECTIVE: To investigate the relations of the productivity stability of to the
      homogenization of Ginkgo biloba cells by single cell clones. METHOD: Using plant
      single cell plate culture technique. RESULTS: Adding 500 ml.L-1L-glutamine in the
      medium increased greatly the cell plating efficiency (PE), and within the range
      0.5-5.0 x 10(4) Cell.ml-1 of the initial cell density, the PE increased with the
      increment of the cell density. Of the 48 cell clones obtained, the GKB content in
      G-22 clone reached 0.099%; and most of the clones remain stable in growth and GKB
      production during subcultures. CONCLUSION: During the cell and tissue culture of
      G. biloba, the application of plant single cell cloning technique helps to a
      certain extent solve the problem of productivity instability of ginkgolide.

PMID- 12516450
TI  - [Studies on initial infection sources and channels of black spot on Panax
      notoginseng (Burk.) F.H. Chen].
AB  - OBJECTIVE: To probe into the occurring and developing regularities of black spot
      on Panax notoginseng for disease control. METHODS: After artificial inoculation,
      observation and analysis on the planting plots were conducted regularly. RESULTS:
      The main infection sources include diseased seeds, seedlings, plants and soils.
      On the plot of new cropping, the initial infection sources are diseased seeds and
      seedlings while diseased plants and soils with pathogens are the main sources
      onplot of old cropping. CONCLUSION: Wiping out the infection centre and sources
      are the major effective means for control of black spot on P. notoginseng.

PMID- 12516451
TI  - [Studies on non-anthraquinones in Rheum officinale Baill].
AB  - OBJECTIVE: To investigate the non-anthraquinones from the root and rootstock of
      Rheum officinale. METHOD: The chemical constituents were obtained from the 85%
      alcohol extract of the radix and rhizoma of R. officinale by column
      chromatography and identified by spectroscopic analysis. RESULT: Ten non
      anthraquinones were obtained, of which eight were identified by spectroscopic
      analysis as rheosmine, daucosterol, d-catechin, 6-cinnamoylisolindleyin, (-)
      epicatechin-3-O-gallate, resveratrol-4'-O-beta-D-(6"-O-galloyl)-glucopyranoside,
      gallic acid, D-sorbitol. CONCLUSION: Compounds rheosmine and D-sorbitol were
      obtained from the genus Rheum for the first time.

PMID- 12516452
TI  - [Studies on chemical constituents of Phyllanthus urinaria L].
AB  - OBJECTIVE: To investigate the chemical constituents of Phyllanthus urinaria.
      METHOD: Various chromatographic techniques were employed for isolation and
      purification of the constituents. The structures were elucidated by chemical and
      spectral analyses. RESULT AND CONCLUSION: Fourteen compounds were isolated and
      seven of them were identified as corilagin(I), rutin(II), brevifolincarboxylic
      acid(VI), isostrictiniin(IX), geraniin (X), gallic acid(XI) and ellagic acid
      (XII). Compound VI was found from P. urinaria for the first time and compound IX
      was found from genus Phyllanthus for the first time.

PMID- 12516453
TI  - [Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD].
AB  - OBJECTIVE: To establish a method for the determination of notoginsenoside R1 in
      Radix Notoginseng. METHOD: The HPLC-ELSD method was used for the determination.
      Chromatographic conditions: Shimpack CLC-ODS column(6.0 mm x 150 mm),
      acetonitrile-water(30:70) as the mobile phase, and Shimadzu LC-6A with SEDEX 55
      ELSD detector. RESULT: The recovery rate is 101.57% and relative standard
      deviation 1.98%. CONCLUSION: The method is reliable for the quality control of
      Radix Notoginseng.

PMID- 12516454
TI  - [Effect and mechanism of active fraction A guizhi decoction on dual-directional
      thermoregulation: effect on heat shock protein in hypothalamus of rats].
AB  - OBJECTIVE: To investigate the effect of active fraction A in Guizhi Decoction
      (Fr.A) on dual-directional thermoregulation and its mechanism of influencing heat
      shock protein (HSP) in hypothalamus. METHOD: Using Western blot method to measure
      HSP of hypothalamus in febrile and hypothermal rats. RESULTS: Regulating the body
      temperature in dual-direction, Fr.A could antagonize the decrease of HSP contents
      of hypothalamus in hypothermal rats induced by aminopyrine, and abate the HSP
      content in febrile rats induced by yeast. CONCLUSION: Fr.A adjusts the body
      temperature through regulating the contents of HSP of hypothalamus in febrile and
      hypothermal rats.

PMID- 12516455
TI  - [Effects of total flavones of metasequosia on left ventricular hypertrophy due to
      pressure overload in rats].
AB  - OBJECTIVE: To determine the preventive and regressive effects of total flavones
      of metasequosia (TFM) on left ventricular hypertrophy in rats. METHOD: Left
      ventricular hypertrophy was inducedin by partial ligation of abdominal aorta. The
      rats were given ig TFM(4, 40, 400 mg.kg-1.d-1) for six weeks. RESULT: TFM
      markedly reduced the HW/BW, LVW/BW, myofibril diameter and Ca2+ content in left
      ventricles but the systolic blood pressure (SBP) in rats wasn't obviously
      influenced. CONCLUSION: TFM can prevent and reverse the left ventricular
      hypertrophy due to pressure overload in rats. The mechanism may be related to its
      calcium antagonistic properties.

PMID- 12516456
TI  - [Inhibitory effect of paeonol on lipid peroxidational reaction and oxidational
      decorate of low density lipoprotein].
AB  - OBJECTIVE: To observe the effects of paeonol(Pae) on lipid peroxidational
      reaction and oxidational decorate of low density lipoprotein(LDL). METHOD: The
      rat model of hyperlipidaemia was established by feeding high lipid diet with
      cholesterol for 6 weeks. The contents of malondialdehyde(MDA) and oxidized low
      density lipoprotein(OX-LDL) were measured by thiobarbituric acid reactive
      substance(TBA) method and sandwich method of enzyme-linked immunosorbent assay
      for detection of polyclone antibody. LDL of serum in healthy person was separated
      by improve precipitate method. RESULTS: Pae(300, 150 mg.kg-1) could reduce
      significantly the levels of MDA of serum, aorta and liver; Pae(300 mg.kg-1)
      decreased obviously the content of OX-LDL of plasma; Pae(1,000, 200, 40
      micrograms.ml-1) refrained markedly the course of oxidational decorate of LDL of
      serum in healthy person. CONCLUSION: Pae could reduce the levels of MDA and OX
      LDL in hyperlipidaemia rats, and refrain the oxidational decorates of LDL of
      serum in healthy person.

PMID- 12516457
TI  - [Inhibitory activity of Dianthus superbus L. and 11 kinds of diuretic Traditional
      Chinese medicines for urogenital Chlamydia trachomatis in vitro].
AB  - OBJECTIVE: To detect the susceptibility of urogenital chlamydia trachomatis(CT)
      to 12 kinds of diuretic traditional Chinese medicines. METHODS: The inhibitory
      activity of these medicines for CT was detected by microculture technique of
      McCoy cell in vitro. RESULTS: All the 12 kinds of diuretic traditional Chinese
      medicines had inhibitory activities for urogenital CT, with minimal inhibitory
      concentrations (MICs) from 0.122 mg.ml-1 to 62.5 mg.ml-1. The activities of
      Dianthus superbus L., Poria cocos(Shcw.) Woft, Polyporus umbellatus and
      Artemissia capillaris were stronger. The number and volume of CT inclusions
      reduced gradually and disappeared finally with the rise of concentration.
      CONCLUSION: All the 12 kinds of diuretic traditional Chinese medicines possess
      some inhibitory activity for urogenital CT.

PMID- 12516458
TI  - [Advances in the study on effect of traditional Chinese medicine on gene
      expression].
AB  - OBJECTIVE: To review the progresses in the study on the effect of traditional
      Chinese medicine (TCM) on gene expression. METHOD: Consulting more than 20
      domestic relevant documents of recent years and summarizing several
      representative kinds of TCM. RESULT AND CONCLUSION: The curative effect of TCM
      has something to do with its bioactive composition that promotes the regulation
      of gene expression; and the continued study on this mechanism of regulation may
      contribute to the modernization of TCM theory.

PMID- 12516459
TI  - [A study on thermal decomposition mechanism and quality analysis of pearl
      powder].
AB  - OBJECTIVE: To establish a rapid and convenient method for distinguishing genuine
      from sham of pearl powder as well as appraising its quality preliminarily.
      METHOD: Thermogravimetry and differential thermogravimetry. RESULT: The TG and
      DTG curves can be divided into two characteristic regions. The first step ranges
      from 250 to 380 degrees C with a weight loss of about 3%, resulting from the
      denaturalization and decomposition of organic matter in the powder; and the
      second step from 600 to 780 degrees C with a weight loss of about 40% resulting
      from the decomposition of calcium carbonate in the powder. CONCLUSION: According
      to the two characteristic regions on TG and DTG curves along with corresponding
      parameters, pearl powder can be appropriately authenticated. Being related
      directly to the contents of organic matter in pearl powder, the first step is an
      important criterion for quality appraisal.

PMID- 12516460
TI  - [A revision of species and distribution of medicinal plants in Guizhou Province].
AB  - OBJECTIVE: To reconfirm the medicinal plants of Aristolochiaceae,
      Caryophyllaceae, Menispermaceae, Illiciaceae and Magnoliaceae found in Guizhou
      Province. METHODS: Making a textual research on the Latin names and geographical
      distribution of medicinal plants recorded in <<Medicinal Material Resources of
      Guizhou>>. RESULT: Of the above-cited medicinal plants 27 species are absent in
      Guizhou Province, 21 species and 2 varieties misnamed in Latin, and 8 species
      newly supplemented. CONCLUSION: At present in Guizhou Province there are 22
      species and 2 varieties of Aristolochiaceae, 29 species, 1 variety and 1
      subspecies of Caryophyllaceae, 23 species and 2 varieties of Menispermaceae, 7
      species of Illiciaceae, and 24 species and 1 subspecies of Magnoliaceae.

PMID- 12516461
TI  - [Hairy root induction and in vitro cultivation of Pueraria lobata willa. ohwi].
AB  - OBJECTIVE: To study the hairy root induction and hormone-free in vitro liquid
      cultivation of Pueraria lobata (Willd) Ohwi. METHOD: Co-cultivation of super
      virulent Agrobacterium rhizogenes R1601 with P. lobata leaves in vitro. RESULTS:
      Hairy roots of rapid growth, high branches and plagiotropism developed vigorously
      on the surface of leaves, exhibiting rapid growth and resistance to kanamycin in
      hormone-free medium in vitro. CONCLUSION: A method of hairy root induction with
      A. rhizogenes as well as a system hairy root liquid cultivation in vitro for P.
      lobata have been established.

PMID- 12516462
TI  - [Studies on flavone constituents of Erigeron breviscapus (Vant.) Hand.-Mazz].
AB  - OBJECTIVE: To study the chemical constituents of Erigeron breviscapus. METHOD:
      The constituents were separated and purified by column chromatography with silica
      gel, and identified by IR, MS, NMR and physical data. RESULT: Five compounds were
      isolated and identified as 3, 5, 6, 4'-tetrahydroxy-7-methoxy flavonoid(I); 5, 7,
      4'-trihydroxy flavonoid(II); 3, 5, 6, 7, 4'-pentahydroxy flavonoid(III);
      scutellarein (IV) and 5, 7, 4'-trihydroxy flavanone(V). CONCLUSION: Compounds I,
      III and V were isolated from this plant for the first time.

PMID- 12516463
TI  - [Studies on chemical constituents of leaves of Salix matsudana Koidz and their
      influence on lipolysis].
AB  - OBJECTIVE: To study the chemical constituents of the leaves Salix matsudana and
      their influence on norepinephrine-induced lipolysis. METHOD: The chemical
      constituents were studied by means of chemical methods and spectral analysis.
      Rat's epididymal lipocytes were used to observe the effect of these constituents
      on the lipolysis promoted by norepinephrine (NE). RESULT: Three constituents were
      isolated from the leaves of S. matsudana, and identified as apigenin-7-O-beta-D
      glucopyranoside, luteolin-7-O-beta-D-glucopyranoside, luteolin-3'-methyl ether-7
      O-beta-D-glucopyranoside, of which two can increase the release of free fatty
      acids(FFA) in the process lipolysis promoted by NE. CONCLUSION: All the three
      constituents were isolated from the leaves of Salix spp. for the first time.

PMID- 12516464
TI  - [Studies on chemical constituents of Ligustrum obtusifolium Sieb. et Zucc].
AB  - OBJECTIVE: To study the chemical constituents in the twigs and leaves of
      Ligustrum obtusifolium. METHOD: Seven compounds were isolated from the ethanol
      extract of the twigs and leaves by polystyrene resin RA and silica gel column
      chromatography. The structures were identified by spectral analysis. RESULT: Of
      the seven compounds isolated six were identified as luteolin, luteolin-4'-O-beta
      D-glucopyranoside, (+)-pinoresinol, (+)-pinoresinol-4'-O-beta-D-glucopyranoside,
      (+)-medioresinol and (-)-olivil. CONCLUSION: luteolin, luteolin-4'-O-beta-D
      glucopyranoside, (+)-pinoresinol, (+)-medioresionnol and (-)-olivil were isolated
      from this plant for the first time.

PMID- 12516465
TI  - [Determination of cinnamaldehyde in Guizhi by HPLC].
AB  - OBJECTIVE: To establish a HPLC method for the determination of cinnamaldehyde in
      Guizhi. METHOD: Cinnamaldehyde was separated by a Kromasil C18 column (4.6 mm x
      200 mm) with a mobile phase of acetonitrile-0.1% phosphoric acid solution(48:52)
      and an UV detection wavelength of 285 nm. RESULT: The calibration curve was
      linear in the range of 0.004-0.02 microliter.ml-1, with a correlation coefficient
      of 0.9996. The average recovery was 100.7%(n = 5), and RSD 0.3%(n = 6).
      CONCLUSION: The method is simple and accurate.

PMID- 12516466
TI  - [Protective effect of xinxin capsule on learning and memory impairment in mice].
AB  - OBJECTIVE: To investigate the effect of Xinxin Capsule on the scopolamine or
      ethanol induced impairment of learning and memory retention in mice. METHOD: Step
      through and Morris Water-maze methods, wer used to the protective effect of
      Xinxin Capsule(0.4, 0.8, 1.6 g.kg-1, ig, 16 d) on the scopolamine or ethanol
      induced impairment of learning and memory retention in mice. RESULT: The
      Capsule(0.8, 1.6 g.kg-1, ig,) can turn over the Scope so as to induce the
      impairment of learning, and the Capsule((0.4, 0.8, 1.6 g.kg-1, ig) can improve
      the ethanol induced impairment of memory retention in mice. CONCLUSION: Xinxin
      Capsule helps regain as well as impair the learning and memory retention in mice.

PMID- 12516467
TI  - [Effects of qufengshi prescription on release of hydrogen peroxide and
      interleukin-1 from peritoneal macrophage in adjuvant arthritis rat].
AB  - OBJECTIVE: To study the mechanism of antiarthritis effects of Qufengshi
      Prescription. METHODS: Adjuvant arthritis (AA) was applied as pathological model
      of rheumatoid arthritis and prednisone was used as positive control. RESULTS: The
      Prescription at high and medium dosages significantly decreased the rising level
      of hydrogen peroxide and interleukin-1 in AA rats (P < 0.05), the potency being
      similar to prednisone. CONCLUSION: Qufengshi Prescription Could reduce the rising
      level of interleukin-1 and hydrogen peroxide in AA rats, which may be part of
      mechanism of the antiarthritis effect.

PMID- 12516469
TI  - [Reconsideration about fibroblast growth factor and soft tissue repair].
AB  - OBJECTIVE: To further explore the effects of fibroblast growth factor on soft
      tissue repair. METHODS: Based on the data from our experiments and clinical trial
      and data from other reports, a further reconsideration about fibroblast growth
      factor and soft tissue repair was demonstrated, including embryonic development,
      histology, animal experiments, clinical trial and prospect. RESULTS: Amounts of
      basic and clinical data showed that fibroblast growth factor was needed in
      embryonic development. Exogenous fibroblast growth factor could accelerate wound
      healing. CONCLUSION: Fibroblast growth factor is a bioactive protein which can
      obviously promote wound healing, it has broad prospects of clinical application.

PMID- 12516468
TI  - [Protective effect of bajitian oligosaccharide on PC12 cells lesioned by
      corticosterone].
AB  - OBJECTIVE: To study the possible mechanism of antidepressant effect of Bajitian
      oligosaccharide (MW-97). METHODS AND RESULTS: After incubating with the PC12
      cells in the presence of corticosterone(2 x 10(-4) mol.L-1) for 48 h, it was
      found that MW-97 could protect PC12 cells from the lesion done by corticosterone
      in a concentration-dependent manner. Furthermore, using RT-PCR mediated cross
      species partial cDNA cloning, it was found that MW-97 and desipramine(DIM)
      increased NGF, BDNF mRNA in the frontal cortex after chronic administration for
      21 days, meanwhile, BDNF mRNA in hippocampus was also increased. CONCLUSION: The
      cytoprotective effect of MW-97 consists in the possible mechanism of its
      antidepressant action, while the increasing expression of neurotrophic factors
      (NGF, BDNF mRNA) may be contributes to the cytoprotective effect.

PMID- 12516470
TI  - [Clinical observation on changes of fibroblast growth factor in burn wounds].
AB  - OBJECTIVE: To investigate the changes of fibroblast growth factor (FGF) in burn
      wounds. METHODS: The FGF expression in the center of wound granulation, the edge
      of wound, the healed part of wound, the normal skin of patients, and the heal
      course of second degree burn wounds were detected by immunohistochemical methods.
      RESULTS: The expression intensity of FGF was different in the different sites of
      third degree burn wounds. The highest contents of FGF was in the center
      granulation of burn wounds, the less was in the borderline of wound and healed
      skin, and the least was in the healed skin. FGF expression mainly concentrated in
      the middle layer of wound, and almost no FGF expression in normal skin. The most
      FGF expression was occurred at 14 days after injury in second degree of burn
      wound. CONCLUSION: The changes of FGF in wounds are closely related to the wound
      healing, and rational use of FGF can promote wound healing.

PMID- 12516471
TI  - [The effect of heparin on wound healing of second-degree burned rats].
AB  - OBJECTIVE: To study the effect of therapeutic effect of heparin on wound healing
      of second-degree burned rats. METHODS: Deep second-degree burns with 20% of total
      body surface were made in 20 rats, which were randomly divided into 2 groups. The
      experimental group was treated subcutaneously injection with 1 ml of heparin 100
      U/kg and saline solution, and the control group was treated with 1 ml of saline
      solution, once a day until complete healing of the burned wound. The healing time
      were compared, the growth of granulation tissue and collagen fibers were
      evaluated under light microscope, and the growth of fibroblasts were observed
      under electronic microscope. RESULTS: All rats survived, the healing time of
      experimental group (22.8 +/- 1.87 days) were much shorter than that of control
      group (26.2 +/- 2.82 days) (P < 0.005). Light microscope observation showed that
      the growth of granulation tissue and collagen fibers of experimental group were
      much better than that of control group, and electronic microscope also showed
      that the fibroblast growth was obviously better in the experimental group.
      CONCLUSION: Subcutaneous injection of heparin can promote wound healing.

PMID- 12516472
TI  - [Modulation of nerve growth factor on wound healing of burn].
AB  - OBJECTIVE: To investigate the effect of nerve growth factor(NGF) on the burn
      wound healing and to study the mechanism of burn wound healing. METHODS: Six
      domestic pigs weighting around 20 kg were used as experimental animals. Twenty
      four burn wound, each 2.5 cm in diameter, were induced on every pigs by scalding.
      Three different concentrations of NGF, 1 microgram/ml, 2.5 micrograms/ml, 5
      micrograms/ml were topically applied after thermal injury, and saline solution
      used as control group. Biopsy specimens were taken at 3, 5 and 9 days following
      treatment and immunohistochemistry method was used to detect the epidermal growth
      factor(EGF), EGF receptor (EGF-R), NGF, NGF receptor (NGF-R), NGF, NGF-R, CD68
      and CD3. RESULTS: The expression of EGF, EGF-R, NGF, NGF-R CD68 and CD3 were
      observed in the experimental group, especially at 5 and 9 days, no expression of
      those six items in the control group. CONCLUSION: NGF can not only act directly
      on burn wound, but also modulate other growth factors on the burn wound to
      accelerate the healing of burn wound.

PMID- 12516473
TI  - [Characteristics of bFGF and TGF-beta expression in dermal chronic ulcers and
      hypertrophic scars and their effects on tissue repair].
AB  - OBJECTIVE: To localize the distribution of basic fibroblast growth factor (bFGF)
      and transforming growth factor-beta(TGF-beta) in tissues from dermal chronic
      ulcer and hypertrophic scar and to explore their effects on tissue repair.
      METHODS: Twenty-one cases were detected to localize the distribution of bFGF and
      TGF-beta, among them, there were 8 cases with dermal chronic ulcers, 8 cases with
      hypertrophic scars, and 5 cases of normal skin. RESULTS: Positive signal of bFGF
      and TGF-beta could be found in normal skin, mainly in the keratinocytes. In
      dermal chronic ulcers, positive signal of bFGF and TGF-beta could be found in
      granulation tissues. bFGF was localized mainly in fibroblasts cells and
      endothelial cells and TGF-beta mainly in inflammatory cells. In hypertrophic
      scar, the localization and signal density of bFGF was similar with those in
      granulation tissues, but the staining of TGF-beta was negative. CONCLUSION: The
      different distribution of bFGF and TGF-beta in dermal chronic ulcer and
      hypertrophic scar may be the reason of different results of tissue repair. The
      pathogenesis of wound healing delay in a condition of high concentration of
      growth factors may come from the binding disorder of growth factors and their
      receptors. bFGF may be involved in all process of formation of hypertrophic scar,
      but TGF-beta may only play roles in the early stage.

PMID- 12516474
TI  - [The experimental study of intracellular actin in the scar fibroblasts].
AB  - OBJECTIVE: To study the relationship between intracellular actin and scar
      contracture. METHODS: Fibroblasts from 10 cases of hypertrophic scar and 5 cases
      of keloid were cultured in vitro. Total actin, filamentous actin(F actin),
      globular actin (G actin) and the ratio of F to G actin(F/G) were measured by
      densitometry after differential extraction and separation by polyacrylamide gel
      electrophoresis in the presence of sodium sulfate. RESULTS: Total actin, F actin,
      G actin and F/G in hypertrophic scar fibroblasts were 2.38 ng/10(4) cells, 0.98
      ng/10(4) cells, 1.42 ng/10(4) cells and 0.68 respectively, while in keloid
      fibroblasts were 1.68 ng/10(4) cells. 0.46 ng/10(4) cells, 1.26 ng/10(4) cells,
      and 0.36 respectively. There was significant differences between two tissues
      fibroblasts in the items of total actin, F actin, G actin, and F/G (P < 0.01),
      while no significant difference in G actin (P > 0.05). CONCLUSION: Total
      intracellular actin, F actin, and F/G may play an important role in the scar
      contracture. The hypertrophic scar and keloid can be distinguished by the
      contents of total intracellular actin, F actin and F/G.

PMID- 12516475
TI  - [Expression of platelet derived growth factor receptor-beta in fibroblasts of
      keloid].
AB  - OBJECTIVE: To investigate the expression and distribution of platelet derived
      growth factor receptor-beta(PDGFR-beta) in normal skin and keloid and to discuss
      its biological function in keloid formation. METHODS: 1. To detect the expression
      and distribution of PDGFR-beta in normal skin and keloid tissue by
      immunohistochemistry; 2. To detect the receptor expression in vitro by Flow
      cytometry (FCM); 3. To detect the subcellular distribution of receptor by Laser
      confocal microscope. RESULTS: 1. Immunohistochemistry showed that normal skin and
      keloid tissue were almost the same in expression but different in distribution of
      PDGFR-beta; 2. There was more expression of PDGFR-beta in normal fibroblasts than
      that in keloid fibroblasts in vitro by FCM; 3. Laser confocal microscope revealed
      that the PDGFR-beta concentrated on the surface of cell membrane in keloid
      fibroblasts, but in normal skin fibroblasts, the receptors were coagulated on the
      nuclear membrane and intranucleus. CONCLUSION: Compared with the fibroblasts in
      vivo, there was a difference of the PDGFR-beta expression in fibroblasts in
      vitro, more expression of PDGFR-beta in normal fibroblast than that in keloid
      fibroblast in vitro; and the subcellular distribution of PDGFR-beta was different
      in normal skin and keloid fibroblasts. The characteristics of the expression and
      distribution of PDGFR-beta in keloid may contribute to the formation of keloid.

PMID- 12516476
TI  - [Effect of cytokines on repair of tendon injury].
AB  - OBJECTIVE: The review the effect of cytokines on repair of tendon injury and the
      relevant mechanism. METHODS: By broadly consulting recent issues about cytokines
      involved in tendon repair, a variety of cytokines with effects in repairing
      injured tendon was made and the possible mechanisms were summarized, with
      unsolved problems discussed. RESULTS: There were many cytokines participated in
      the procedure of tendon repair, among which insulin-like growth factor (IGF-1),
      transforming growth-beta 1 (TGF-beta 1) played significant roles. Most of the
      relevant researches were limited in experimental study in vitro. CONCLUSION:
      Cytokines possibly can accelerate tendon repair and show great potentials in
      future clinical application.

PMID- 12516477
TI  - [Application of skin and soft tissue expansion in treatment of burn injury].
AB  - OBJECTIVE: To evaluate the application of skin and soft tissue expansion in the
      treatment of deformity due to extensive severe burn injury and repair of severe
      deep electrical burned scalp and skull with fresh wound. METHODS: From 1988, 83
      cases of application of skin and soft tissue expansion were reported. In those
      patients with deformity due to severe burn of large area and with whole nasal
      defect, soft tissue expander was used under the forehead skin graft and venter
      frontalis, followed by reconstruction of nose with the expanded vascularized skin
      flap and carved cartilago costalis as nasal frame. In patients of severe deep
      electrical burned scalp and skull with fresh wound, skin and soft tissue
      expansion were used to repair the wound simultaneously with scalp burn alopecia,
      anesthetics and antibiotics injected into the extracapsular space of the expander
      in case of pain and infection. RESULTS: All of the cases were successfully
      treated with little pain and minimized infection. CONCLUSION: Skin and soft
      tissue expansion in a safe and reliable measure in the treatment of deformity due
      to extensive severe burn injury and repair of severe deep electrical burned scalp
      and skull with fresh wound.

PMID- 12516478
TI  - [Repair of nasal columella defect with long slender tubed flap].
AB  - OBJECTIVE: To introduce the clinical application of long slender tubed flap
      constructed with "bridge" technique in the repair of nasal columella defect.
      METHODS: From March 1968 to August 1998, 18 cases with complicated nasal
      columella defects were repaired with long slender tubed flaps. Among the 18 tubed
      flaps, 13 cases were designed on the medial side of the upper arm and 5 cases on
      the longer cervical region paralleling the clavicle. The tubed flaps were 2.0 to
      2.5 cm wide and 11 to 15 cm long. The length of the "bridge" was 3 to 7 cm.
      RESULTS: No flap necrosis or other complications occurred. Postoperative follow
      up was 3 to 60 months. The reconstructed columellae showed satisfactory contour,
      good texture and color, and satisfactory resistance to injury. CONCLUSION: By
      using the "bridge" technique, tubed flap can be made long and slender enough to
      provide relatively abundant tissue with adequate circulation and delicate
      contour. Combined with strict case selection, long slender tubed flaps can bring
      excellent functional and cosmetic outcomes in the repair of nasal columella
      defects including those with partial defect of the nasal tip, ala, septum, or
      defect of adjacent soft tissue. However, this method is relatively time
      consuming.

PMID- 12516479
TI  - [Treatment of nonunion of scaphoid bone by transfer of radial periosteal bone
      flap pedicled with recurrent branch of radial artery].
AB  - OBJECTIVE: To introduce the operation method of treatment of nonunion of scaphoid
      bone by transfer of pedicled radial periosteal bone flap. METHODS: From Match
      1986, 26 cases with old nonunion of scaphoid bone were treated by transfer of
      radial periosteal bone flap pedicled with recurrent branch of radial artery, the
      size of bone flap was 1.0 cm x 0.4 cm x 0.5 cm. RESULTS: All patients with old
      nonunion of scaphoid bone were healed by first intention, bone union was occurred
      after 2 to 3 months of operation, and wrist joint almost recovered normal
      function. CONCLUSION: It is an effective operation method to treat nonunion of
      scaphoid bone.

PMID- 12516480
TI  - [The applied anatomy of transposition of the distal dorsal ulna bone flap
      pedicled with dorsal metacarpal artery].
AB  - OBJECTIVE: To investigate the anatomic basis for transposition of the distal
      dorsal ulna bone flap pedicled with dorsal metacarpal artery to repair the defect
      of the 3rd or 4th and 5th metacarpal bone head. METHODS: In 30 adult cadaveric
      upper limbs, the branches and constitutions of the dorsal carpal arterial
      networks were observed. RESULTS: The dorsal carpal arterial networks were
      consisted of the dorsal carpal branches of ulnar and radial arteries, the
      terminal branches of posterior interosseous artery and the dorsal carpal branch
      of anterior interosseous artery, and then the 2nd, 3rd, 4th dorsal metacarpal
      branches were originated from the networks. The dorsal metacarpal branches were
      anastomosed with the deep branches of deep palmar arch to constitute the dorsal
      metacarpal artery. CONCLUSION: Transposition of the distal dorsal ulna bone flap
      pedicled with the 3rd, 4th dorsal metacarpal arteries can be used in repairing
      the defect of 3rd, 4th and 5th metacarpal bone head.

PMID- 12516481
TI  - [Study of apoptosis in the male rat spermatogenic cells after vasostomy].
AB  - OBJECTIVE: To investigate the effect of vasostomy on apoptosis in the male rat
      spermatogenic cells after vasoligation. METHODS: Model of vasoligation and
      vasostomy in male rat was established, and then terminal deoxynucleotidyl
      transferase-mediated dUTP nick labelling technique to detect the apoptosis of
      spermatogenic cells at 4, 8, 12, 16 weeks after vasostomy. RESULTS: The number of
      apoptotic cells in vasostomy group was significantly lower than that of
      vasoligation group since 8 weeks after vasostomy(P < 0.05). The number of
      apoptotic cells in 8 and 12 weeks after vasostomy were significantly higher than
      that in prevasoligation(P < 0.05). 16 weeks after vasostomy, the number of
      apoptotic cells restored to the level same as that in prevasoligation stage.
      CONCLUSION: Vasostomy can reverse the apoptosis of spermatogenic cells due to
      vasoligation.

PMID- 12516482
TI  - [Application of silks as scaffolds for three-dimensional culture of
      chondrocytes].
AB  - OBJECTIVE: To observe the effects of silks on attachment, shape and function of
      chondrocytes cultured in vitro. METHODS: The silks from silk worm cocoons were
      digested by trypsin and coated with polylactic acid to from three dimensional
      scaffolds for rabbit rib chondrocyte culture. The growth and shape of
      chondrocytes were observed with phase contrast microscopy, scanning electron
      microscopy. RESULTS: The chondrocytes were adhered to silks slowly after
      chondrocytes were seeded into silk scaffolds and cells fixed on silks well 1 or 2
      days later. Cells began to proliferate after 3 days and multiplicative growth was
      observed on the 6th day. Microholes of silk scaffolds were filled with
      chondrocytes 2 weeks later. Scanning electron microscopy showed that there was a
      lot of extracellular matrix surrounding cells. CONCLUSION: Silks are ideal for
      attachment, growth and function maintenance of chondrocytes, and silks can be
      used as scaffolds for chondrocytes in three dimensional culture.

PMID- 12516483
TI  - [The influence of basic fibroblast growth factor on the adhesion characteristics
      of osteoblasts in rabbit].
AB  - OBJECTIVE: To investigate the influence of basic fibroblast growth factor (bFGF)
      on adhesion characteristics of osteoblasts, aimed at the important problem in
      bone tissue engineering of how to promote the adherence of osteoblasts to
      extracellular matrix materials. METHODS: 5 ng/ml, 10 ng/ml, 50 ng/ml, 100 ng/ml,
      200 ng/ml bFGF were used to induce bone marrow stromal-derived osteoblasts of
      rabbit for 24 hours before incubation, and the common culture medium as the
      control. The attached cells were calculated with stereology method at 0.5 hour,
      1st hour, 2nd hour, 4th hour, 8th hour after seeding. RESULTS: The number of
      attached cells was significant higher in the experimental group when induced by
      10 ng/ml bFGF than that in the control group (P < 0.01); the number did not
      increase with the increase of bFGF concentration and there was no significant
      difference between the experimental group induced by 100 ng/ml bFGF and control
      group, and the number was even obviously lower in the experimental group when
      induced by 200 ng/ml than the control group (P < 0.01). CONCLUSION: bFGF can
      influence the adhesion characteristics of osteoblasts, 10 ng/ml bFGF can promote
      the adherence of osteoblasts to matrix materials, but 200 ng/ml bFGF may inhibit
      cell adhesion.

PMID- 12516484
TI  - [Bibliometric analysis on tissue engineering research literatures].
AB  - OBJECTIVE: To comprehend the progress of tissue engineering research and
      speculate its developmental trends. METHODS: MEDLINE search was conducted to
      retrieve the papers published between 1987 to 1999 under the main headings of
      tissue engineering. Years, nationalities, languages, journals, authors and
      heading frequencies of 314 papers were analyzed by bibliometrics. RESULTS: Since
      1990, the number of tissue engineering research literatures had doubled, and
      papers between 1998 and 1999 made up 57.96% of the total papers. All papers came
      from 15 nations, in 6 languages and 140 journals; 64.97% came from United States
      and 25.79% from England, Netherlands and Germany; 93.95% was in English; 42.04%
      was published on 15 journals. Vacanti JP and 19 other authors presented 5 to 24
      papers. Heading frequencies were cytology 22.89%, transplantation 13.30%,
      scaffolds and extracellular matrixes 11.72%, implanting 10.60%, polymers 8.91%,
      potential applications 8.91%, artificial substitutes 6.88%, tissue culture 6.70%
      and biogenetics 4.96%. CONCLUSION: Tissue engineering literatures mainly come
      from United States, England, Netherlands and Germany. English is the major
      language. J Biomed Mater Res and 14 other journals are important journals about
      tissue engineering research. Vacanti JP and 19 other authors are prolific
      authors. Cytology, transplantation, scaffolds and extracellular matrixes and
      implanting are hot topics and key points on tissue engineering research.

PMID- 12516485
TI  - [The RYR1 genotype of Chinese inbred pigs].
AB  - OBJECTIVE: Porcine stress syndrome (PSS) is one kind of molecular genetics defect
      diseases of pig which will cause malignant hyperthermia syndrome (MHS) and is the
      first index should be excluded in screening of a pig species for
      xenotransplantation. It was reported that mutation of pig rynodine receptor(RYR1)
      gene is the main reason for PSS. In this study, RYR1 genotypes of the Chinese
      Banna mini pig inbred line and inbreeding closed colony Wuzhishan pig were
      investigated with polymerase chain reaction-restriction endonuclease fragment
      length polymorphism (PCR-RFLP) technique. METHODS: Antevenocaval whole blood
      samples were collected from 50 Banna mini-pig inbred-line(BMI), 15 inbreeding
      Wuzhishan pig (WZSP) and 25 Neijiang pigs (NJP) as negative control, the primer
      were designed and synthesized, PCR reaction was conducted following the sequence
      of 94 degrees C (1 min), 58 degrees C (1 min) and 72 degrees C (1 min) for 30
      cycles. The PCR products were digested with restriction endonuclease HhaI and
      then electrophoresis check. RESULTS: A 659 bp DNA fragment was amplified with
      these two primers, the HALNN sample fragment was cut into fragments as 493 bp and
      166 bp individually after the digestion, indicates no point mutation at site
      1,843 in RYR1 gene in all tested BMI pig and WZSP. Namely, the RYR1 genotype of
      50 cases of BMI and 15 cases of WZSP were HALNN, therefore their phenotype is PSS
      negative. CONCLUSION: It indicates that the genotype of Banna mini pig inbred
      line and inbreeding Wuzhishan pig are HALNN therefore PSS absolutely negative,
      the group penetrance is 0. This is consistent with experimental observation. It
      suggests that Banna mini pig inbred line and inbreeding Wuzhishan pig may be the
      alternative donor for xenotransplantation.

PMID- 12516486
TI  - [Medical application of hyaluronic acid and its derivatives].
AB  - OBJECTIVE: To review the recent advances of hyaluronic acid and its derivatives
      in medical application. METHODS: Recent original articles related to hyaluronan
      derivatives and their medical applications were retrieved extensively. RESULTS:
      Hyaluronic acid and its derivatives play important roles in visosurgery,
      arthritis therapy, prevention of adhesion, drug delivery, soft-tissue dilation,
      and percutaneous embolization. CONCLUSION: Development of hyaluronan derivatives
      may widen their medical application.

PMID- 12516487
TI  - [Volume replacement during anesthesia. Colloids, crystalloids].

PMID- 12516488
TI  - [Comparison of efficacy and complications of 27G and 29G Sprottte needles for
      subarachnoid anesthesia].
AB  - OBJECTIVE: Post-dural puncture headache and lumbar backache are related to needle
      gauge and type of point used. We aimed to determine whether the incidence of post
      dural puncture headache and lumbar backache could be reduced by using fine gauge
      pencil-point Sprotte 27G and 29G needles. We also studied increases in technical
      difficulty with these needles and whether or not reducing needle gauge affected
      anesthetic quality. PATIENTS AND METHOD: Three hundred eighty-nine patients
      undergoing orthopedic or lower abdominal surgery were randomly assigned to two
      groups for dural puncture using two Sprotte needles: 27G or 29G. We recorded time
      to perform puncture, number of re-insertations of the needle, number of times the
      technique was abandoned and anesthetic efficacy. On the second and seventh days,
      the patients were interviewed by telephone to check for the presence and severity
      of post-dural puncture headache or lumbar backache. RESULTS: The technical
      difficulty was greater with the Sprotte 29G needle, as shown by significant
      differences in time taken to perform the puncture and the number of re-insertions
      (p < 0.05). Anesthetic quality was the same in both groups and the percentage of
      failures was 0.5% for both. Five percent of patients in the 27G group and 3% in
      the 29G group experienced slight or moderate headache on the second day. No cases
      of severe cephalea were reported. Lumbar backache was reported on the second day
      by 26% and 18.5% of the patients in the 27G and 29G groups, respectively, but the
      rates decreased to 4.5% and 0.5% on the seventh day. The differences were
      significant, favoring the 29G needle. CONCLUSIONS: The use of 29G pencil-point
      needles can be recommended to reduce the incidence of headache and lumbar
      backache in the postoperative period, in spite of the greater technical
      difficulty involved, given that quality of anesthesia is maintained.

PMID- 12516489
TI  - [Preoperative diclofenac does not reduce pain of laparoscopic cholecystectomy].
AB  - OBJECTIVE: To study the safety and efficacy of diclofenac for preemptive
      analgesia in the first 24 hours after elective laparoscopic cholecystectomy
      (ELC). PATIENTS AND METHODS: This prospective, randomized, placebo-controlled,
      double-blind study enrolled 90 patients of both sexes undergoing ECL. The
      patients were 17 to 76 years old and weighed between 45 and 100 Kg (ASA I and
      II). Assignment was to one of the following groups. A control group received
      diclofenac before and after surgery (DD) as follows: diclofenac 1 mg/Kg i.m. 60
      minutes before surgery and a loading dose of 0.35 mg/Kg i.v. after surgery
      followed by continuous infusion of 1.5 mg/Kg over 24 hours. The study group
      received diclofenac and placebo (DP) as follows: diclofenac 1 mg/Kg i.m. 60
      minutes before surgery and infused saline solution after extubation. A second
      control group received placebo before surgery and diclofenac afterwards (PD) as
      follows: a physiological solution was given intramuscularly 60 minutes before the
      operation and diclofenac was given after extubation as in the DD group. Pain
      intensity was assessed on a visual analog scale at four times: 1 hour (T1), 6
      hours (T2), 12 hours (T3) and 24 hours (T4) after extubation. At those times we
      also recorded the need for rescue analgesia and side effects. Arterial blood
      gases and vital signs were recorded 1 hour before surgery (T0) and at T4.
      RESULTS: Pain intensity at T1 was 2.67 +/- 0.54, 2.82 +/- 0.63 and 2.88 +/- 0.58
      for the DD, DP and PD groups, respectively (p = 0.96). The differences in mean
      pain between T1 and T2, T3 and T4 were -0.2 +/- 0.66, -0.7 +/- 0.51 and 0.0 +/-
      0.72 in the DD group (p = 0.723); -0.9 +/- 0.60, -0.4 +/- 0.57 and -1.3 +/- 0.65
      in the DP group (p = 0.578); and -1.0 +/- 0.59, -0.5 +/- 0.77 and -1.0 +/- 0.69
      in the PD group (p = 0.816). No significant differences in pain intensity or need
      for rescue analgesia were observed. Although 22 side effects were observed in
      group DD, 21 in DP and 21 in PD, none was serious. CONCLUSIONS: Simple preemptive
      analgesia with 1 mg/Kg i.m. of diclofenac 60 minutes before induction of
      anesthesia does not decrease pain intensity or the need for rescue analgesia in
      the first 24 hours after ELC.

PMID- 12516490
TI  - [Course of postoperative pain in laparoscopic cholecystectomy under multimodal
      anesthesia-analgesia in ambulatory care].
AB  - OBJECTIVE: To evaluate the evolution of postoperative pain and convalescence in a
      group of patients undergoing elective laparoscopic cholecystectomy under a
      multimodal anesthesia-analgesia treatment protocol. MATERIAL AND METHOD: Eighty
      four consecutive patients undergoing elective laparoscopic cholecystectomy were
      given intramuscular ketoprofen during induction, anesthesia, with minimal use of
      opioids, and intraperitoneal irrigation with bupivacaine. We assessed the rate of
      conversion to hospitalization, hospital stay in hours, duration of the pain-free
      interval, oral analgesics per day at home, and intensity of postoperative pain
      and physical activity daily on a visual analog scale. RESULTS: The procedures
      were carried out on an outpatient basis in 90.5% of the cases, and the mean
      postoperative hospital stay was 7.2 +/- 0.9 hours. Eight patients required an
      overnight stay. No postoperative analgesics were required by 27.3% of the
      patients. Patients requiring analgesics had pain-free intervals lasting 17.3 +/-
      11.8 hours after discharge. On the third day after surgery 80% had used no
      analgesics and over 75% had no pain or only minor pain. On the fourth
      postoperative day 50% were able to perform activities of daily living without
      help, and 50% returned to work on the eleventh day after surgery. CONCLUSIONS:
      The multimodal analgesia-anesthesia treatment proposed allows a high percentage
      of laparoscopic cholecystectomies to be performed on an outpatients basis. The
      protocol provides good control of postoperative pain and nausea and rapid return
      to habitual activity.

PMID- 12516491
TI  - [Locoregional anesthesia and drugs that affect hemostasis. Suggestions of the
      expert meeting in the ESRA Congress in Barcelona].
AB  - Growing interest in the effect of hemostasis-altering medications on regional
      anesthetic techniques was analyzed recently in a review article suggesting
      certain safety measures, by Llau and colleages in Revista Espanola de
      Anestesiologia y Reanimacion. Since that review, however, it has become necessary
      to extend the discussion of clinical issues, based on information presented at
      the Eighth Local Meeting of the European Society for Regional Anesthesia (ESRA)
      of May 2002. There, participants debated the most controversial aspects, with
      attention to practical questions such as temporal safety margins and approaches
      to take given certain platelet antiaggregants, fibrinolytics or drug
      combinations. This paper faithfully presents the suggestions made by participants
      at the meeting. As most anesthesiologists expressed the need to set guidelines
      for fibrinolytics, the main issues related to those drugs in regional anesthesia
      are reviewed.

PMID- 12516492
TI  - [Treatment of postoperative pain in heart surgery].
AB  - Postoperative pain ranks among the major problems surgical patients face and it
      has been taken particularly seriously in recent years. Catecholamine release in
      response to nociceptive stimulus is associated with higher rates of hemodynamic,
      respiratory, endocrine, metabolic and immune system complications that worsen the
      prognosis. Pain after cardiac surgery in the adult has been investigated little,
      however, probably because it is less intense than pain after thoracotomy. The
      importance of providing good perioperative analgesia requires us to have an in
      depth understanding of the characteristics of such pain, the therapeutic
      armamentarium available and the technique to be used. Although intravenous
      analgesia is the most widely applied approach to postoperative pain management,
      the development of devices for patient controlled analgesia and the advantages of
      epidural analgesia require us to analyze what the ideal technique might be. The
      advantages of strict pain control after cardiac surgery oblige us to place
      greater emphasis on such management among our main postoperative objectives.

PMID- 12516493
TI  - [Acute myocardial infarction in the postoperative period following
      pneumonectomy].
AB  - A 72-year-old man, smoker, with insuline-dependent diabetes and dislipemia
      underwent left pneumonectomy. Several episodes of intraoperative hemodynamic
      instability associated with electrocardiographic ST segment alterations were
      attributed to surgical manipulation; ischemia was not suspected.
      Cardiorespiratory failure, related to extensive anterior infarction, developed a
      few minutes after admission to the postoperative intensive care unit (PICU).
      Cardiopulmonary resuscitation and mechanical ventilation were required. The
      patient responded to treatment with beta blockers, platelet antiaggregants and
      statins. Tube was removed a few hours later and the patient was discharged from
      the PICU on the fifth day. Pneumonectomy has a high rate of morbidity and
      mortality, with complications mainly arising in the lung and heart. Risk from
      anesthesia is considered to be great in this procedure, and for that reason it is
      essential to identify intraoperative myocardial ischemia so that it can be
      treated aggressively. In patients at high cardiovascular risk who undergo lung
      resection, intraoperative episodes of myocardial ischemia are associated with a
      high incidence of postoperative miocardial infarction. Therefore, careful
      postoperative monitoring is needed and measures should be taken to prevent
      angina. Early extubation should be avoided.

PMID- 12516494
TI  - [Blood reflux through the catheter when trying catheterization of the subclavian
      vein is not a reliable sign in case of hemothorax].
AB  - A 36-year-old man suffered chest and neurovascular trauma, soft-tissue injury to
      the left arm, and trauma to facial bones and extremities. He was hemodynamically
      unstable and responded poorly to blood transfusion and vasoactive medication.
      Pneumothorax was suspected. When a tube was inserted into the left hemithorax,
      1500 mL of blood was drained. A chest film revealed hemothorax and a contusion on
      the left lung, but no rib fractures. An attempt to catheterize the left
      subclavian vein yielded reflux, and blood was then transfused. The patient
      continued to be highly unstable and an additional 1000 mL of blood was drained.
      Exploratory thoracotomy revealed a ruptured subclavian vein, location of the
      venous catheter in the pleural cavity, and a fracture of the first left rib.
      After chest injury leading to hemothorax, reflux upon catheterization of the
      ipsilateral subclavian vein is not a sure sign of correct tip placement.
      Additional means for checking placement, such as assessing pressure wave
      morphology, should be used. A fracture of the first rib, which may not be evident
      on a chest x-ray, often causes a vascular lesion and thoracic hemorrhage.
      Incorrect insertion of a subclavian catheter may then follow.

PMID- 12516495
TI  - [Cauda equina hemisyndrome after intradural anesthesia with bupivacaine for hip
      surgery].
AB  - A 68-year-old man underwent hip surgery under subarachnoid anesthesia with
      bupivacaine and fentanyl to replace an acetabular component. Two days after
      surgery the patient developed unilateral cauda equina syndrome, affecting five
      nerve roots (L4 to S3), with no sphincter involvement. Two and a half years
      later, the lesion had become permanent. We discuss the possible origin of the
      condition, suggesting differential diagnoses such as mechanical problems
      (position-mobilization) and anesthetic toxicity.

PMID- 12516496
TI  - [Changing preoperative fasting may modulate the postoperative stress response].

PMID- 12516497
TI  - [Two additional cases of anesthesia in patients with narcolepsy].

PMID- 12516498
TI  - [Anesthesia considerations in type III mucolipidosis].

PMID- 12516499
TI  - [HELLP syndrome diagnosed after mild to moderate epigastric pain in the third
      trimester of pregnancy].

PMID- 12516500
TI  - [Tremors, cramps, and myalgia after the use of ephedrine].

PMID- 12516501
TI  - [19th century concepts of anesthesiology in a work on 21st century surgery].

PMID- 12516502
TI  - Osteoporosis guidelines.

PMID- 12516503
TI  - Implanon.

PMID- 12516504
TI  - Editor's reply.

PMID- 12516505
TI  - Using a division based diabetes register to target patients for enhanced primary
      care care planning.

PMID- 12516506
TI  - Eat less, walk more. Enjoyable eating for type 2 diabetes.
AB  - BACKGROUND: Lifestyle management is the basis of diabetes treatment. In most
      cases, healthy eating, activity and weight loss can result in significant
      improvements in blood glucose, lipids and overall health. General practitioners
      have a key role in encouraging and supporting patients with diabetes to make
      lifestyle changes. OBJECTIVE: This article outlines the general lifestyle
      nutritional recommendations of type 2 diabetes and provides practical ideas for
      GPs to help patients achieve lifestyle goals. DISCUSSION: Although lifestyle is
      the cornerstone of diabetes management, it is the most difficult part of
      management to implement. Adherence to recommended eating and activity schedules
      is low. A complete dietary assessment requires input from a dietitian and support
      from the GP.

PMID- 12516507
TI  - Cannabis control. An approach to cannabis use and dependence.
AB  - BACKGROUND: Cannabis use is widespread in our community. Dependence on cannabis
      may be associated with significant mental and physical harms. OBJECTIVE: This
      article aims to give an overview of the adverse effects of cannabis use and
      guidelines for management of cannabis dependence. DISCUSSION: General
      practitioners can manage cannabis dependence from a harm minimisation framework
      using motivational interviewing and other counselling measures. Occasionally,
      pharmacologic approaches may be used with the caveat that they should be brief
      and carefully monitored.

PMID- 12516508
TI  - Alcohol misuse and dependence. Assessment and management.
AB  - BACKGROUND: General practitioners play a vital role in the prevention of alcohol
      related morbidity and mortality. The earlier an alcohol problem is diagnosed, the
      better the treatment outcome. OBJECTIVE: This article aims to provide GPs with
      practical guidelines on the assessment and management of patients with hazardous
      alcohol use and dependence. DISCUSSION: There is good evidence that early and
      brief intervention by a GP is most effective in reducing alcohol consumption in
      patients with hazardous or harmful drinking. In patients with alcohol dependence,
      pharmacotherapies such as naltrexone and acamprosate, in conjunction with a
      comprehensive rehabilitation program, are beneficial in a proportion of patients.

PMID- 12516510
TI  - Health benefits of quitting.

PMID- 12516509
TI  - How to provide effective smoking cessation advice in less than a minute without
      offending the patient.
AB  - BACKGROUND: General practitioners have the opportunity, credibility and authority
      to provide smoking cessation advice and are effective in assisting smokers to
      quit. Despite their potential, GPs identify just over half the smokers in their
      practice and counsel approximately one-third to quit. Implementation of smoking
      cessation advice has not improved in the past 10 years despite the availability
      of evidence based guidelines. Effective smoking cessation advice should include
      both the 5As (Ask, Assess, Advise, Assist, Arrange) and the development of a
      supportive infrastructure within the practice setting. OBJECTIVE: This article
      outlines the rationale for GP involvement in assisting smokers to quit, advises
      how GPs can provide smoking cessation advice in less than a minute, the main
      barriers to quitting smoking, and the core activities in the 5As. DISCUSSION:
      General practitioner effectiveness in smoking cessation can be improved by
      adopting a systematic approach to identifying smoking status, more effective
      engagement of smokers by separating information from the 'moral imperative', use
      of brief motivational interviewing techniques and appropriate pharmacotherapy,
      and use of the QUIT line and other smoking cessation resources.

PMID- 12516511
TI  - The identification and management of the drug impaired doctor.
AB  - BACKGROUND: Problem drug use occurs within the medical fraternity as it does in
      other parts of the population. However, doctors have traditionally been
      discouraged from admitting vulnerability and frequently fail to recognise or
      respond to early signs of problem alcohol and drug use. OBJECTIVE: This article
      aims to identify sequential strategies to assist the doctor to detect and
      intervene early when problem drug use arises in themselves or a colleague.
      DISCUSSION: Where treatment and monitoring is instituted early in problem drug
      use, outcomes are typically positive while late acknowledgment commonly results
      in sanctions for the impaired practitioner and greater risk to patients. Medical
      boards in Australia have developed supportive mechanisms for doctors to
      facilitate early management. Procedures are aimed at maintaining or restoring
      ability to work while maintaining public confidence.

PMID- 12516512
TI  - The art of dealing with complaints.
AB  - Complaints against medical practitioners are relatively frequent. Appropriate
      management of complaints is an important part of good practice management. This
      article provides some guidelines for general practitioners on how to respond to
      patient complaints.

PMID- 12516513
TI  - Compassion and patient centred care.
AB  - BACKGROUND: The essence of medicine is a relationship based upon a concern for
      suffering. Western medicine, arising from a modernistic philosophy, has a
      tradition of paternalistic 'doctor centred' care. There are significant
      criticisms of this approach. OBJECTIVE: Drawing on postmodern perspectives, this
      article discusses the nature of patient centred care. Patient centred care
      requires a reconciliation of the patient's and doctor's agenda via attention to
      communication, power and patient autonomy. Patient centred care has been defined
      by six domains: the illness experience, the context, finding common ground,
      partnership, health promotion, and consultation limitations. DISCUSSION: Patients
      strongly desire patient centred care. It has been associated with improved
      patient and doctor satisfaction, greater compliance, fewer investigations,
      referrals and malpractice complaints, and no change in consultation time. Patient
      centred care exerts a positive influence on health outcomes and is especially
      applicable in general practice, providing an efficacious and compassionate
      response to suffering.

PMID- 12516514
TI  - Reducing falls in community dwelling elderly. The role of GP care planning.
AB  - BACKGROUND: Falls in the elderly are common and often result in injury. A large
      body of evidence has identified the risk factors for falls, and indicates that
      strategies to prevent falls need to be targeted and multidisciplinary. OBJECTIVE:
      This article aims to present the epidemiology of falls in the elderly, discuss
      current knowledge of ways of approaching the problem, and using an evidence based
      approach, explore how general practitioners can identify elderly persons at risk
      of falls, and implement the use of a care planning model into general practice.
      DISCUSSION: General practitioners are well placed to identify patients at risk of
      a fall, and the new Enhanced Primary Care items for care planning provide
      opportunities to improve the way in which we manage these patients.

PMID- 12516515
TI  - Longevity: does what goes up always have to come down?

PMID- 12516516
TI  - Allied health professionals providing psychological treatments in general
      practice settings. What options are there?
AB  - BACKGROUND: This article is based on a literature review and discussion document
      developed for the Commonwealth Department of Health and Aging to assist in its
      deliberations on the structure of the Better Outcomes in Mental Health Program
      (BOMH). OBJECTIVE: This article examines issues regarding the engagement of
      allied health professionals in the delivery of specific time limited and evidence
      based counselling interventions in the general practice setting. DISCUSSION:
      Specific issues examined include employment and administrative arrangements,
      citing of these services, communication between general practitioners and
      counsellors, as well as clinical supervision and support.

PMID- 12516517
TI  - Psychiatry's missing link--mental injury.

PMID- 12516518
TI  - Complementary therapies in general practice.

PMID- 12516519
TI  - Characteristics of Victorian general practitioners who practise complementary
      therapies.
AB  - BACKGROUND: To compare the characteristics of Victorian general practitioners who
      practise and do not practise complementary therapies. METHOD: A self administered
      postal survey sent to 800 Victorian GPs. RESULTS: The response rate was 64%.
      There were no statistically significant differences between complementary therapy
      practitioners and nonpractitioners in the number of patients seen per week, urban
      versus rural location, solo versus group practice or Fellowship of the Royal
      Australian College of General Practitioners. In some complementary therapies,
      practising GPs tended to be male, full time and older. DISCUSSION: Victorian GPs
      who practise complementary therapies are on the whole not from the fringes of the
      medical community. The reasons why GPs include complementary therapies in their
      practice cannot be answered by this study.

PMID- 12516520
TI  - A conceptual model for capacity building in Australian primary health care
      research.
AB  - BACKGROUND: Many general practitioners and primary health care practitioners lack
      research and evaluation skills. In response, the Australian Government has funded
      important capacity building initiatives. AIM: To propose a conceptual model to
      assist these initiatives. MODEL: Four groups of research involvement are
      suggested: nonparticipants; participating (as part of a research team);
      managing/training (either leading research, or in formal training to do so); and
      academic (with, or leading toward, a doctorate). We outline six guiding
      principles for research capacity building: 1) a whole system approach, 2)
      accommodating diversity, 3) reducing barriers to participation, 4) enabling
      collaboration, 5) mentoring, and 6) networking. CONCLUSION: This model forms a
      framework to help plan and evaluate research capacity building initiatives.

PMID- 12516521
TI  - The discovery and development of atorvastatin, a potent novel hypolipidemic
      agent.
AB  - The search for potent and efficacious inhibitors of the enzyme HMG-CoA reductase
      (HMGRI) was the focus of considerable research in the 1980s. Building on the
      discovery of the fungal metabolite-derived inhibitors, mevastatin, lovastatin,
      pravastatin and simvastatin, a number of totally synthetic inhibitors were
      discovered and developed. This manuscript describes the discovery and development
      of one of those synthetic inhibitors, atovastatin calcium, currently marketed in
      the United States as LIPITOR. This inhibitor was designed based in part on
      molecular modeling comparisons of the structures of the fungal metabolites and
      other synthetically derived inhibitors. In addition to development of the
      structure-activity relationships which led to atorvastatin calcium, another
      critical aspect of the development of this area was the parallel improvement in
      the chemistry required to prepare compounds of the increased synthetic complexity
      needed to potently inhibit this enzyme. Ultimately, the development of several
      chiral syntheses of enantiomerically pure atorvastatin calcium was accomplished
      through a collaborative effort between discovery and development. The impact of
      the progress of the required chemistry as well as external factors on internal
      decision-making with regards to the development of atorvastatin calcium will be
      discussed.

PMID- 12516522
TI  - Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the
      treatment of neurodegenerative diseases.
AB  - Apoptosis has been proposed as a mechanism of cell death in Alzheimer's,
      Huntington's and Parkinson's diseases and the occurrence of apoptosis in these
      disorders suggests a common mechanism. Events such as oxidative stress, calcium
      toxicity, mitochondria defects, excitatory toxicity, and deficiency of survival
      factors are all postulated to play varying roles in the pathogenesis of the
      diseases. However, the transcription factor c-jun may play a role in the
      pathology and cell death processes that occur in Alzheimer's disease. Parkinson's
      disease (PD) is also a progressive disorder involving the specific degeneration
      and death of dopamine neurons in the nigrostriatal pathway. In Parkinson's
      disease, dopaminergic neurons in the substantia nigra are hypothesized to undergo
      cell death by apoptotic processes. The commonality of biochemical events and
      pathways leading to cell death in these diseases continues to be an area under
      intense investigation. The current therapy for PD and AD remains targeting
      replacement of lost transmitter, but the ultimate objective in neurodegenerative
      therapy is the functional restoration and/or cessation of progression of neuronal
      loss. This chapter will describe a novel approach for the treatment of
      neurodegenerative diseases through the development of kinase inhibitors that
      block the active cell death process at an early transcriptional independent step
      in the stress activated kinase cascade. In particular, preclinical data will be
      presented on the c-Jun Amino Kinase pathway inhibitor, CEP-1347/KT-7515, with
      respect to it's properties that make it a desirable clinical candidate for
      treatment of various neurodegenerative diseases.

PMID- 12516523
TI  - Discovery of second generation quinazolinone non-nucleoside reverse transcriptase
      inhibitors of HIV-1.
AB  - An intensive research effort to identify potent, viable drugs for the management
      of acquired immunodeficiency syndrome (AIDS) resulted in the development of
      SUSTIVA (efavirenz), the first non-nucleoside reverse transcriptase inhibitor
      (NNRTI) approved by the FDA as a preferred first-line therapy. The search for
      NNRTIs that possess a broader activity spectrum against mutant viral forms of
      human immunodeficiency syndrome type-I reverse transcriptase culminated in the
      discovery that trifluoromethyl-containing quinazolin-2(1H)-ones possess potent
      activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs). This
      chapter reviews the discovery and structure activity relationships that resulted
      in the identification and subsequent preclinical and clinical development of four
      quinazolinone NNRTIs at the DuPont Pharmaceuticals Company.

PMID- 12516524
TI  - Molecular modeling of opioid receptor-ligand complexes.

PMID- 12516525
TI  - Satisficing in hypothesis generation.
AB  - Research in hypothesis generation suggests that people might act as satisficers
      and be less likely to generate plausible alternative hypotheses when they already
      have a hypothesis that accounts for the data in hand. Three experiments simulated
      scientific hypothesis development. In all 3, participants who had been given a
      hypothesis consistent with available data generated proportionally fewer of the
      simplest alternative hypotheses than participants given no such satisficing
      hypothesis. Furthermore, participant satisficing occurred regardless of whether
      the provided hypothesis was generated a priori or post hoc and despite high
      incentives for completeness. Limitations and implications of these findings are
      discussed for hypothesis development and the practice of taking post hoc
      hypotheses suggested by one's results and presenting them as a priori hypotheses.

PMID- 12516526
TI  - Individual differences in working memory during reading with and without
      parafoveal information: a moving-window study.
AB  - We examined individual differences in working memory appearing in the effective
      visual field size while reading Japanese text. Working memory capacity was
      measured by a Japanese reading span test, and the subjects were divided into high
      and low-score groups. Reading performance was measured by reading time,
      comprehension, and eye movements using a variable moving window through which the
      subject could read areas of the Japanese text. As the window size decreased, the
      reading time increased significantly. High-span subjects showed better
      performance in reading time, comprehension, and fixation duration than low-span
      subjects even in small visual fields. Interestingly, high-span subjects appear to
      show better information integration during reading, whereas low-span subjects
      showed less integration without parafoveal vision. These findings suggest that
      reading performance was better for subjects with larger working memory resources
      in a parafoveal restriction condition.

PMID- 12516527
TI  - Automaticity in reading and the Stroop task: testing the limits of involuntary
      word processing.
AB  - We investigated the parameters of involuntary word reading in the Stroop task in
      7 experiments. Experiments 1-4 varied response modality and the presence of
      congruent word trials in a test of the claim that presenting a Stroop color word
      with only one letter in the target color eliminates the Stroop effect.
      Experiments 5 and 6 addressed the roles of spatial attention and orthographic
      processing as possible mechanisms behind the reduction of Stroop effects with the
      single-letter format. Experiment 7 investigated the limits of involuntary reading
      under optimal conditions for selective processing of rectangular color patch
      targets. We found that the single-letter format reduced but never eliminated
      Stroop effects, spatial attention but not orthographic processing plays a role in
      the effect of the single-letter format, and word reading is not completely
      prevented even with austere presentation conditions. We conclude with a defense
      of the involuntariness criterion for automaticity in the Stroop task,
      particularly when word reading is viewed in the context of a skilled performance.

PMID- 12516528
TI  - Disambiguating conscious and unconscious influences: do exclusion paradigms
      demonstrate unconscious perception?
AB  - Does exclusion failure--responding with previously presented words despite
      instructions to avoid doing so--demonstrate unconscious influences? This article
      examines exclusion-based evidence for unconscious perception. I propose an
      alternative signal detection theory (SDT) framework that can account for
      exclusion failure and ostensibly convergent qualitative differences without
      positing additional unconscious perceptual mechanisms. In the proposed SDT model,
      exclusion failure is a criterion artifact, similar to classic SDT-based critiques
      of subjective threshold approaches. However, it is suggested that exclusion
      approaches do demonstrate that response strategies are applied only to above
      criterion stimuli and thereby illustrate important qualitative differences
      between two conscious processes: phenomenal awareness itself and higher-order
      (i.e., metacognitive) decision processes.

PMID- 12516529
TI  - Configural biases and reversible figures: evidence of multilevel grouping
      effects.
AB  - Four experiments sought to identify the processes underlying 2 classes of
      grouping effects that are readily produced with a hierarchical figure type known
      as ambiguous triangles. Previous work has shown that aligning small equilateral
      triangles in particular configurations can both facilitate and interfere with
      observers' ability to report the pointing direction of the individual triangles.
      We determined that selectively adapting the observer to low-frequency gratings of
      the same orientation as the aligned triangles markedly altered the interfering
      and facilitative effects of the global configuration only when an accuracy
      measure of performance was used. When a response latency measure was used, no
      effect of the same adaptation condition was found. Results are discussed in terms
      of multiple levels of grouping effects in the visual system and the differential
      sensitivity of these levels to basic neural adaptation.

PMID- 12516530
TI  - The robustness of medical expertise: clinical case processing by medical experts
      and subexperts.
AB  - Medical specialists confronted with problems in their domain of expertise do not
      rely on intentional causal reasoning, using explicit principles or rules. Rather,
      reasoning is an automatic process, using knowledge in an encapsulated mode. Less
      clear is what happens when medical specialists encounter problems outside their
      specialties. To shed light on this issue, we asked cardiologists and
      pulmonologists to evaluate 4 clinical cases, 2 in the domain of cardiology and 2
      in pulmonology. Their task was to study, diagnose, recall, and explain the signs
      and symptoms of the clinical case descriptions. The cardiologists and
      pulmonologists alike processed cases in their specialties faster and more
      accurately, but recall and pathophysiological explanations did not reveal
      significant differences. These results suggest that medical specialists do not
      process cases outside their specialties in a qualitatively different mode from
      cases within their specialties.

PMID- 12516531
TI  - The importance of intraoperative evaluation in the management of anorectal
      atresia.
AB  - We report a neonate with anorectal atresia in whom preoperative evaluation prior
      to definitive operation revealed a short gap atresia. However, bidigital
      evaluation at operation revealed a septal atresia that was easily perforated from
      below through the anus. Unnecessary division of the anorectal sphincter complex
      was thus avoided.

PMID- 12516532
TI  - Evaluating the management of diabetic retinopathy in a teaching center.
AB  - PURPOSE: To evaluate the efficacy of the management of diabetic retinopathy (DR)
      in the teaching center of the University Eye Clinic of Patras in Greece. METHODS:
      From 1989 to 1999, 302 patients with type I (5.3%) and type II (94.7%) diabetes
      mellitus (DM) were examined. Standard examination and treatment protocols were
      employed. Examinations and laser treatment were done by trainee specialists,
      under the supervision of the head physician (N.Ph), during their rotation in the
      retina and vitreous disorders outpatient department. RESULTS: At baseline
      examination, 17.9% of the eyes had no DR, 71.7% had nonproliferative DR, and
      10.4% had proliferative DR. In 34.4%, no laser treatment followed. The other
      65.6% underwent focal and/or grid laser and/or panretinal photocoagulation and/or
      vitrectomy. At the final examination, DR was still the same in 63.1% of the eyes,
      progression had occurred in 34.1%, and regression in 2.8%. Type I DM patients'
      eyes had a higher prevalence of proliferative DR at the final examination than
      type II DM eyes. There was also a significant correlation between progression of
      DR and duration of DM, insulin treatment for DM, and elevated glycosylated
      hemoglobin (HbA1c). CONCLUSIONS: Having applied standard examination and
      treatment protocols, the efficacy of the management of our diabetic patients was
      consistent with international standards, even though patients were treated mostly
      by doctors in training.

PMID- 12516533
TI  - Anesthesia through a novel retrobulbar catheter provides perioperative pain
      control for 24 h after pars plana vitrectomy.
AB  - PURPOSE: The purpose of this study was to assess the retrobulbar catheter
      technique for perioperative pain control in pars plana vitrectomy. METHODS: One
      hundred consecutive pars plana vitrectomies (duration 20-220 minutes) in 88
      patients (age range 37-88 years) were performed by the same surgeon under
      retrobulbar anesthesia using a commercially available retrobulbar needle.
      Initially, 7 ml of mepivacaine 2% were injected, a 28-gauge flexible catheter was
      introduced into the retrobulbar space and the needle was withdrawn. The catheter
      was removed 24 h after surgery. Intraoperatively and postoperatively, the
      patients were asked to rate pain using a numerical scale from 0 to 10. When pain
      was more than grade 3, 2 ml of a local anesthetic were re-injected through the
      catheter. RESULTS: A first re-injection was given intraoperative/y 53.0 +/- 34.6
      minutes after the start of surgery during 35/100 procedures, and second and third
      injections were needed during 12 /100 and 4/100 procedures, respectively. The
      first postoperative re-injection was given 3.9 +/- 1.5 hours after the start of
      surgery in 54 procedures, and second and third injections were carried out in
      35/100 and 10/100 procedures respectively. CONCLUSIONS: The results suggest that
      a temporary indwelling retrobulbar catheter allows long-lasting titratable local
      anesthesia during pars plana vitrectomy and titratable postoperative analgesia.

PMID- 12516534
TI  - Increase patient acceptance of financial options.

PMID- 12516535
TI  - The annexin-1 knockout mouse: what it tells us about the inflammatory response.
AB  - The 37kDa protein annexin 1 (Anx-1; lipocortin 1) is a glucocorticoid-regulated
      protein that has been implicated in the regulation of phagocytosis, cell
      signalling and proliferation, and postulated to be a mediator of glucocorticoids
      action in inflammation and in the control of anterior pituitary hormone release.
      Immuno-neutralisation or antisense strategies support this hypothesis as they can
      reverse the effect of glucocorticoids in several systems. We recently generated a
      line of mice lacking the Anx-1 gene noting that some tissues taken from such
      animals exhibited an increased expression of several proteins including COX-2 and
      cPLA2. In models of experimental inflammation, Anx-1(-/-) mice exhibit an
      exaggerated response and a partial or complete resistance to the anti
      inflammatory effects of glucocorticoids. Several other anomalies were noted
      including abnormal leukocyte adhesion molecule expression, an increased
      spontaneous migratory behaviour of PMN in Anx-1(-/-) mice and a resistance in Anx
      1(-/-) macrophages to glucocorticoid inhibition of superoxide generation. This
      paper reviews these and other data in the light of the development of the 'second
      messenger' hypothesis of glucocorticoid action.

PMID- 12516536
TI  - New developments in work-related asthma.
AB  - Although work-related asthma is the most commonly recognized occupational lung
      disease, the condition remains underrecognized and underreported. New-onset
      occupational asthma and work aggravated asthma can have deleterious medical and
      socioeconomic consequences for the individual. Although interpretation and
      comparison between studies are hampered by the use of variable definitions of WRA
      and criteria for the diagnosis, as many as 20% of cases of new or aggravated
      adult asthma has important work-related factors. Thus, all asthmatic patients
      should be asked about their work, if their respiratory symptoms are worse when
      they work, or if a new job/exposure preceded the onset of symptoms. A series of
      longitudinal inception and apprentice cohort studies were undertaken to address
      significant weakness in the previous medical literature. These studies are just
      beginning to produce results, and provide strong evidence for asthma caused by
      exposure to specific occupational environments. They have begun to produce new
      understanding of the risk factors for developing OA, the natural history of OA
      and immune sensitization, and the existence of the healthy worker effect. New,
      non-invasive measures of airway inflammation have been developed with the
      potential for broad applications in the field of WRA. Although the measurement of
      exhaled NO and induced sputum analysis are primarily used as research tools,
      their place in clinical practice is likely to become clearer. These methods also
      have the potential to elucidate the various pathophysiologic mechanisms involved
      in WRA and may broaden our concept of occupational exposures that can initiate
      the onset of asthma.

PMID- 12516537
TI  - Genetic and exposure risks for chronic beryllium disease.
AB  - Exposure to beryllium results in beryllium sensitization, or development of a
      beryllium-specific, cell-mediated immune response, in 2% to 19% of exposed
      individuals. Sensitization usually precedes the development of the scarring lung
      disease, chronic beryllium disease. The development of granulomatous inflammation
      in patients with CBD is associated with the production of numerous inflammatory
      cytokines, including IFN-gamma, IL-2, and TNF-alpha (see Fig. 1). In some
      individuals this can result in increased granulomatous inflammation and a more
      severe form of the disease. Although the exposure response relationship in
      sensitization and disease is nonlinear, in some studies, higher exposures were
      associated with higher rates of sensitization and CBD. Machinists usually have
      higher levels of beryllium exposure and increased risk of developing
      sensitization and disease. The impact of the physicochemical properties of
      beryllium, such as form, solubility, and particle size, on the risk of
      sensitization and disease are less well understood. It is clear from numerous
      studies that genetic susceptibility affects risk of beryllium-related health
      effects. The role of HLA-DPB1 Glu69 in the proliferative response to beryllium
      and risk of sensitization has been the most well-studied. Some genes, such as
      Glu69, are important in the development of an antigen-specific, cell-mediated
      immune response to beryllium or sensitization, whereas others may be important in
      the development of beryllium-specific granulomatous inflammation or CBD (see Fig.
      1). Two copies of the Glu69 gene may be a disease-specific genetic risk factor.
      The TNF-alpha -308 A variant is associated with beryllium-stimulated TNF-alpha
      production, which, in turn, is associated with more severe CBD. Whether the TNF
      alpha -308 A is a genetic risk factor in CBD, sensitization, or more severe
      disease still needs to be determined. It is likely that sensitization and CBD are
      multigenetic processes, and that these genes interact with exposure to determine
      risk of disease. Current genetic markers are not ready for clinical use as a
      screening test for beryllium-related health effects because of the low
      specificity of the markers and the low prevalence of BeS and CBD.

PMID- 12516538
TI  - Chemical treatment of root surfaces in periodontal therapy.

PMID- 12516539
TI  - Abstracts of the 16th Annual Symposia on Etiology, Pathogenesis, and Treatment of
      Parkinson's Disease and Other Movement Disorders.

PMID- 12516540
TI  - The TGF-beta response to Leishmania chagasi in the absence of IL-12.
AB  - Cure of leishmaniasis requires a type 1 immune response characterized by IFN
      gamma production. Leishmania major infection leads to a type 2 response
      suppressing cure of susceptible BALB/c mice, and L. major causes an exacerbated
      type 2 response in mouse strains with a gene knockout (KO) such that they lack IL
      12p40 (IL-12KO mice). In contrast, type 1 responses are inhibited by TGF-beta
      without Th2 cell expansion in BALB/c mice infected with L. chagasi. We questioned
      whether the type 2 or the TGF-beta response would dominate during L. chagasi
      infection of IL-12KO mice. C57BL/6 mice developed self-resolving L. chagasi
      infection with abundant IFN-gamma. In contrast, L. chagasi disease was
      exacerbated and IFN-gamma was low in IL-12KO mice. Total TGF-beta was
      significantly higher in IL-12KO than control C57BL/6 mice, but IL-4 and IL-10
      levels were similar. TGF-beta was further augmented in IL-12/IFN-gamma double-KO
      mice. Thus, in contrast to L. major, the TGF-beta response was exacerbated
      whereas type 2 cells were not expanded during L. chagasi infection of IL-12KO
      mice. We conclude that L. chagasi has an inherent propensity to elicit a
      prominent TGF-beta response that either suppresses, or is suppressed by, a type 1
      response. We propose this be termed a "type 3" immune response, which can
      antagonize a type 1 response.

PMID- 12516541
TI  - Abstracts of the 4th International Dystonia Symposium. Atlanta, Georgia, USA.
      June 13-15, 2002.

PMID- 12516542
TI  - Blockade of CD86 in BALB/c mice infected with Leishmania major does not prevent
      the expansion of low avidity T cells.
AB  - The interactions between CD28 and its ligand CD86 are critical for the regulation
      of T cell responses. However, it is not clear whether CD4+ T cells expressing low
      and high avidity TCR are equally dependent on CD28 costimulation for their
      activation and expansion. To address this issue, we have used multimers of I-Ad
      molecules linked to a peptide derived from the Leishmania major homolog for the
      receptor of activated C kinase (LACK) antigen to compare the fate of LACK
      specific CD4+ T cells in Leishmania-infected BALB/c mice which have been treated
      or not with anti-CD86 mAb. Although the administration of anti-CD86 mAb did not
      completely prevent the expansion of LACK-specific T cells, their frequency and
      number were markedly reduced. In mice treated with anti-CD86 mAb as well as in
      control animals, L. major induced the clonal expansion of LACK-specific T cells
      which expressed a canonical low avidity Valpha8/Vbeta4 TCR. Taken together, our
      results suggest that the molecular interactions between CD28 on T cells and CD86
      on APC serve to amplify and modulate T cell responses without promoting breadth
      in the TCR repertoire.

PMID- 12516544
TI  - [Abstracts of the 2nd Croation Internal Medicine Congress with International
      Participation. Opatia, Croatia, 4-8 October 2002].

PMID- 12516543
TI  - Secretion of pro-apoptotic intron 4-retaining soluble HLA-G1 by human villous
      trophoblast.
AB  - One major materno-fetal interface in the human placenta is constituted by the
      syncytiotrophoblast, in contact with maternal blood of the intervillous space,
      which derives from differentiation and fusion of the villous cytotrophoblast
      (vct). In the present work, we purified vct from term placenta by depleting HLA
      class I- and class II-positive cells. We found by RT-PCR that both soluble intron
      4-retaining HLA-G1 (sHLA-G1) and HLA-G2 isoforms were transcribed in purified
      vct. Using different HLA-G-specific mAb, we demonstrated by intracellular flow
      cytometry, Western blotting and ELISA, that sHLA-G1 but no soluble HLA class Ia
      molecule was secreted by vct. We then purified sHLA-G1 from vct culture
      supernatant and found that it exhibited an unusual glycosylation pattern.
      Finally, we showed that such trophoblast-derived sHLA-G1 triggered specific
      apoptosis of activated CD8+ T cells. Taken together, these results demonstrated
      that vct did secrete functional sHLA-G1 in primary culture and suggested that, in
      vivo, sHLA-G1 might be an important immunomodulatory molecule controlling the
      activity of maternal immune effector CD8+ cells circulating in the blood that
      immerses chorionic villi.

PMID- 12516545
TI  - The anti-inflammatory sesquiterpene lactone parthenolide suppresses IL-4 gene
      expression in peripheral blood T.
AB  - Sesquiterpene lactones (SL) derived from Mexican India medicinal plants and
      parthenolide, the major SL from European feverfew, have raised considerable
      interest because of their anti-inflammatory and complex pharmacological action.
      Interleukin-4 (IL-4) is a key cytokine that influences the development of T
      helper 2 cells and plays an important role in the pathogenesis of allergic
      diseases. We show here that the anti-inflammatory parthenolide suppresses IL-4
      expression at the mRNA and the protein levels in a dose-dependent manner. We
      demonstrate that parthenolide blocks NF-kappaB binding to two important IL-4
      promoter regulatory elements and suppresses promoter activity upon T cell
      activation. Differences regarding the effects of parthenolide on expression
      levels of IL-4, IL-2 and IFN-gamma were observed. Parthenolide (2.5 microM) could
      completely suppress IL-4 protein levels secreted in anti-CD3/CD28-stimulated
      peripheral blood T cells from allergic and normal donors. Complete inhibition of
      IL-2 and IFN-gamma requires higher doses of parthenolide. So far, drugs directed
      against IL-4 expression have not been described. This finding raises the
      potential to develop parthenolide to treat IL-4-mediated allergic-like
      inflammation.

PMID- 12516546
TI  - Encephalitogenic T cells use LFA-1 for transendothelial migration but not during
      capture and initial adhesion strengthening in healthy spinal cord microvessels in
      vivo.
AB  - LFA-1 on the surface of encephalitogenic T cells has been suggested to be
      involved in the pathogenesis of experimental autoimmune encephalomyelitis. By
      applying a novel technique of intravital fluorescence microscopy that enables us
      to visualize the interaction of circulating encephalitogenic T lymphoblasts
      within the healthy spinal cord white matter microvasculature in vivo, we
      investigated the possible involvement of LFA-1 on circulating encephalitogenic T
      cells in their multi-step interaction with the blood-brain barrier endothelium in
      vivo. LFA-1 was found to mediate neither the G-protein-independent capture nor
      the G-protein-dependent initial adhesion strengthening of encephalitogenic T cell
      blasts within spinal cord microvessels. In contrast, blocking of LFA-1 on
      encephalitogenic T lymphoblasts resulted in a significantly reduced number of T
      cells firmly adhering within spinal cord microvessels 2 h after injection and in
      a significantly reduced number of T cells subsequently migrating across the
      vascular wall into the spinal cord parenchyme. Our study provides the first
      direct evidence that encephalitogenic T cells use LFA-1 for transendothelial
      migration but not for capture and initial adhesion in spinal cord microvessels in
      vivo.

PMID- 12516547
TI  - Interleukin-10 is crucial for maintenance but not for developmental induction of
      peripheral T cell tolerance.
AB  - To asses the requirement of interleukin (IL)-10 for peripheral CD4 T cell
      tolerance, the IL-10 knockout (KO) was introduced into a T cell receptor
      transgenic mouse model (TCR1) specific for SV40 T antigen (Tag). IL-10-deficient
      TCR1-transgenic mice failed to establish antigen-specific T cell tolerance
      following sequential injections with Tag peptide. Nevertheless, IL-10 was not
      required for the establishment of CD4 T cell tolerance in double transgenic
      RT2/TCR1 mice in which Tag is expressed endogenously under control of the insulin
      promoter. However, in contrast to stable anergy in wild-type RT2/TCR1 mice,
      tolerant T cells in RT2/TCR1/Il-10KO mice could be driven into vigorous
      proliferation by exogenous antigenic stimulation in vivo. The observed
      reactivation of anergic T cell populations in IL-10-deficient mice was only seen
      after in vivo but not in vitro peptide priming, reflecting an important
      regulatory function of IL-10 in the context of the living organism. Taken
      together, these results demonstrate that IL-10 is required to maintain T cell
      tolerance following exposure to enhanced antigenic stimuli but is not essential
      for the induction of self-tolerance.

PMID- 12516548
TI  - Abstracts of the 11th Annual Meeting of the Israel Society for Neuroscience.
      Eilat, Israel, December 15-17, 2002.

PMID- 12516549
TI  - Expression and costimulatory effects of the TNF receptor superfamily members
      CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor
      immune responses.
AB  - This study addresses the relative importance of CD134 (OX40) and CD137 (4-1BB) in
      the costimulation of CD4+ and CD8+ T cells under comparable conditions of
      antigenic stimulation. We demonstrate that CD134 is capable of directly
      costimulating CD8+ T cells. However, costimulation of CD8+ T cells by CD134 is
      less potent than that triggered by CD137. The higher costimulatory activity of
      CD137, when compared with CD134, correlates well with its faster expression
      kinetics and higher levels on CD8+ T cells. Furthermore, induction of CD137
      expression on CD8+ T cells is highly sensitive to low levels of TCR stimulation,
      which is in contrast with CD134. Conversely, CD134 is more effective than CD137
      in costimulating CD4+ T cells. This, however, could not be attributed to
      differential expression. We also demonstrate that the transient nature of CD134
      and CD137 expression on activated CD4+ T cells is the resultof proteolytic
      shedding. Consistent with the greater ability of CD137 to costimulate CD8+ T
      cells, stimulation of CD137 in vivo is considerably more effective than CD134 in
      augmenting anti-tumor immune responses. Therefore, agents that stimulate
      signaling via CD137 are likely to be more useful in clinical conditions where
      highly effective CD8+ CTL responses are required.

PMID- 12516550
TI  - Abstracts of the 25th Annual San Antonio Breast Cancer Symposium. December 11-14,
      2002.

PMID- 12516551
TI  - CpG-ODN-induced inflammation is sufficient to cause T-cell-mediated
      autoaggression against hepatocytes.
AB  - Autoimmune diseases are often associated with microbial infections. Molecular
      mimicry between microbial antigens and self-epitopes has been suggested as a
      mechanism for breaking self-tolerance and induction of autoimmunity. Since
      infections also cause inflammatory responses we explored the role of local
      inflammation in organ-specific autoimmunity. For this purpose, transgenic mice
      were used expressing the MHC class I molecule Kb exclusively on hepatocytes.
      These mice exhibit Kb-specific tolerance as exemplified by the acceptance of Kb+
      grafts. Inflammatory reactions were induced by injection of immunostimulatory
      cytosine-phosphorothioate-guanine (CpG)-rich oligodeoxynucleotides (ODN).
      Application of CpG-ODN is sufficient to break tolerance in vivo, and to cause
      activation of Kb-specific CD8+ T cells and subsequent autoaggression against
      hepatocytes. The CpG-ODN-induced inflammation appears to have two major effects.
      First, it causes infiltration of T cells into the liver parenchyma. Second,
      adhesion and costimulatory molecules are up-regulated on hepatocytes so that the
      infiltrating CD8+ T cells encounter Kb on hepatocytes, which display an APC-like
      phenotype, resulting in activation and tissue damage. Autoimmune hepatitis can be
      maintained for at least eight weeks by repeated application of CpG-ODN but
      subsides after termination of the inflammatory stimulus, suggesting the
      requirement of additional factors for a self-perpetuation of autoimmunity. These
      observations describe an additional pathway for the induction of autoimmunity,
      i.e. in the absence of microbial antigens inflammatory reactions alone can lead
      to infiltration of T cells into organs, resulting in breaking of tolerance and
      autoaggression. Moreover, the results provide evidence that T cell activation can
      take place not only in draining lymph nodes but also directly on parenchymal
      cells.

PMID- 12516553
TI  - Abstracts of the 54th Annual Conference of the Cardiological Society of India.
      December 1-4, 2002. Kochi, Kerala.

PMID- 12516552
TI  - Adhesion of dendritic cells derived from CD34+ progenitors to resting human
      dermal microvascular endothelial cells is down-regulated upon maturation and
      partially depends on CD11a-CD18, CD11b-CD18 and CD36.
AB  - DC are sentinels of the immune system. In order to reach the skin, bone-marrow
      derived DC precursors need to bind and migrate through microvascular endothelial
      cells. Binding of DC toprimary endothelial cells of the skin has not been
      investigated. We therefore determined adhesion of DC at different stages of
      development to human dermal microvascular endothelial cells (HDMEC). DC were
      derived from CD34+ progenitors in cord blood. To enhance DC maturation, a defined
      cocktail of IL-1beta+IL-6+TNF-alpha+PGE2 was applied. Adhesion was quantified by
      fluorimetric and phase-contrast microscopical assays. Significantly more DC
      precursors (tested on day 5 after isolation) than mature DC (spontaneously
      matured or cytokine-cocktail-matured and tested on day 13) bound to unstimulated
      HDMEC. In contrast, the maturation stage of DC had no influence on their binding
      to human umbilical vein endothelial cells. Pretreatment of HDMEC with TNF-alpha
      and IFN-gamma resulted in an enhanced attachment of both DC precursors and mature
      DC. Mature DC lacked expression of CD31, CD36, CD45RA and CLA, and expressed
      lower levels of CD11a, CD11b and CD49d as compared with precursors tested on day
      5. mAb against CD18, CD11a, CD11b, and CD36 markedly inhibited DC binding,
      whereas anti-CLA, anti-DC-SIGN, anti-CD29 and anti-CD49 mAb did not. Our data
      support the hypothesis of immunosurveillance with selective recruitment of blood
      DC precursors to resting and, more so, to inflamed skin. The data have potential
      relevance for anti-cancer immunotherapy strategies favoring the intracutaneous
      application of mature DC.

PMID- 12516554
TI  - Substantial N diversity is generated in T cell receptor alpha genes at birth
      despite low levels of terminal deoxynucleotidyl transferase expression in mouse
      thymus.
AB  - N region diversity in antigen receptors is a developmentally regulated process in
      B and T lymphocytes, which correlates with the differential expression of
      terminal deoxynucleotidyl transferase (TdT). To precisely determine the onset of
      TdT gene activation during T cell differentiation and thymic ontogeny, TdT
      expression was directly detected at the cellular level by in situ hybridization
      and TdT function was assessed by analyzing the distribution of N additions in
      alpha and beta TCR genes at early stages of development. Even though TdT
      transcripts were undetectable at birth, substantial N additions were observed in
      ValphaJalpha junctions and 3 days later in VbetaDbetaJbeta junctions, indicating
      that TdT expression could be induced in immature thymocytes much earlier than
      expected. Indeed low TdT expression level was found in TN3/4 and DP from fetal
      day 17, suggesting that the onset of TdT expression occurs simultaneously in both
      populations and may depend on microenvironmental cues. Moreover significant
      increase in the proportion of thymocytes expressing high levels of TdT mRNA
      during the first week after birth without a similar increase in the level of N
      diversity suggests that TdT expression and TdT function in the generation of N
      diversity are not strictly correlated.

PMID- 12516555
TI  - Italian Society of Biochemistry 47th joint symposia with the British Biochemical
      Society. Palermo, Italy, September 16-19, 2002. Abstracts.

PMID- 12516556
TI  - Qualit-e-Health MEDNET 2002 7th World Conference on the Internet in Medicine.
      Amsterdam, The Netherlands, 4-7 December 2002. Abstracts.

PMID- 12516557
TI  - The preferential ability of B lymphocytes to act as diabetogenic APC in NOD mice
      depends  on expression of self-antigen-specific immunoglobulin receptors.
AB  - B lymphocytes partially contribute to autoimmune type 1 diabetes (T1D) as a
      subset of APC with a preferential ability to trigger pathogenic CD4 T cells. We
      hypothesized that this resulted from the unique ability of B lymphocytes to take
      up pancreatic beta cell proteins through Ig mediated capture. T1D was
      significantly delayed, but not prevented, in a NOD stock in which the B
      lymphocyte Ig repertoire was strongly restricted because of the allelic exclusion
      induced by transgenic Ig molecules specific for the disease irrelevant hen egg
      lysozyme (HEL) protein (NOD.IgHEL mice). However, introducing the Ig(mu)null
      mutation to eliminate the small residual numbers of non-transgenic B lymphocytes
      in the NOD.IgHEL stock strongly suppressed T1D to the same low levels that
      characterize B lymphocyte deficient NOD.Ig(mu)null mice. In contrast to standard
      NOD mice, both the NOD.IgHEL.Ig(mu)null and NOD.Ig(mu)null stocks were unable to
      generate T cell responses against the candidate diabetes autoantigen, glutamic
      acid decarboxylase. These results indicate that Ig-mediated capture of beta cell
      autoantigens accounts for why B lymphocytes have a greater capacity than other
      APC subtypes to trigger diabetogenic T cells. Hence, defects in B lymphocyte, as
      well as T lymphocyte, tolerance induction mechanisms may contribute to T1D in NOD
      mice.

PMID- 12516558
TI  - British Thoracic Society winter meeting. London, United Kingdom, 4-6 December
      2002. Abstracts.

PMID- 12516559
TI  - Amino acid dimorphism and parasite immune evasion: cellular immune responses to a
      promiscuous epitope of Plasmodium falciparum merozoite surface protein 1
      displaying dimorphic amino acid polymorphism are highly constrained.
AB  - Like most other surface-exposed antigens of Plasmodium falciparum, the leading
      malaria vaccine candidate merozoite surface protein (MSP)-1 contains a large
      number of dimorphic amino acid positions. This type of diversity is presumed to
      be associated with parasite immune evasion and represents one major obstacle to
      malaria subunit vaccine development. To understand the precise role of antigen
      dimorphism in immune evasion, we have analyzed the flexibility of CD4 T cell
      immune responses against a semi-conserved sequence stretch of the N-terminal
      block of MSP-1. While this sequence contains overlapping promiscuous T cell
      epitopes and is a target for growth inhibitory antibodies, three dimorphic amino
      acid positions may limit its suitability as component of a multi-epitope malaria
      vaccine. We have analyzed the CD4 T cell responses in a group of human volunteers
      immunized with a synthetic malaria peptide vaccine containing a single MSP-143-53
      sequence variant. All human T cell lines and HLA-DR- or -DP-restricted T cell
      clones studied were exclusively specific for the sequence variant used for
      immunization. Competition peptide binding assays with affinity-purified HLA-DR
      molecules indicated that dimorphism does not primarily affect HLA binding.
      Modeling studies of the dominant restricting HLA-DRB1*0801 molecule showed that
      the dimorphic amino acids represent potential TCR contact residues. Lack of
      productive triggering of the TCR by MHC/variant peptide ligand complexes thus
      seems to be the characteristic feature of parasite immune evasion associated with
      antigen dimorphism.

PMID- 12516560
TI  - Analysis of expressed V(H) genes in persistent polyclonal B cell lymphocytosis
      reveals absence of selection in CD27+IgM+IgD+ memory B cells.
AB  - Persistent polyclonal B cell lymphocytosis (PPBL) is a hematological disorder
      diagnosed predominantly in women, characterized by a polyclonal increase in the
      number of peripheral blood B lymphocytes. Abnormality of the B cell population
      was evidenced by the finding of multiple bcl-2/Ig gene rearrangements and an
      additional long-arm chromosome within a significant proportion of B cells. To
      gain further insight about the developmental status of B lymphocytes in PPBL,
      analysis of cell surface Ig receptors was undertaken. An important expansion of
      the CD27+IgM+IgD+ B cell population was noted in PPBL patients (n=4). When
      investigated by PCR, pattern of heavy chain variable region (VH) genes usage in
      patients (n=6) was shown tobe similar to that observed in healthy individuals
      (n=3). In-depth investigation was then conducted through cloning and sequencing
      of individual VH genes in three of those patients. They were mostly found to be
      mutated (21/29), correlating with the observed increase in CD27 expression, a
      marker of memory B cells. Altogether, these data clearly point out to the exact
      nature of the expanding B cell subset in patients. Finally, analysis of the
      repartition of recombinant versus silent mutations in framework regions (FR) of
      Ig genes showed no evidence of positive antigenic selection following somatic
      hypermutation. Thus, we suggest that a lack of response to physiological signals
      responsible for the elimination of low affinity memory IgM+IgD+ B cells in
      germinal centers could play an important role in the development of PPBL.

PMID- 12516561
TI  - Prescription drug coverage for people with Medicare.
AB  - Medicare currently does not provide outpatient prescription drug coverage. People
      with Medicare who do not have continuous prescription drug coverage face higher
      out-of-pocket expenditures and may not comply with their prescriptions in order
      to save money. This brief explores some of the issues facing beneficiaries
      without drug coverage and describes some of the different options available to
      help offset the costs of prescription medications.

PMID- 12516562
TI  - IL-1beta-induced phosphorylation of PKB/Akt depends on the presence of IRAK-1.
AB  - IL-1, IL-18 and LPS are recognized by specific receptor complexes of the Toll/IL
      1R family, characterized by a common intracellular domain indispensable for
      downstream signaling. Upon ligand binding, these receptors activate the central
      MyD88-IRAK-TRAF6 signaling module, resulting in the activation of NF-kappaB.
      Ligated receptors also induce activation of other signaling cascades, suchas the
      PI3-kinase (PI3-K) and the p38 mitogen-activated protein kinase (MAPK) pathways.
      Unlike the p38MAPK pathway, which couples to the central signaling module, the
      PI3-K pathway seems to directly interact with the receptor molecules. Thus,
      activation of the PI3-K pathway is thought to be independent of the IRAK
      containing signaling module. Employing two cell lines, we show that the PI3-K
      pathways can be activated by IL-1, IL-18 or LPS with comparable, but cell type
      specific kinetics, which can be correlated to biological consequences. This
      indicates that activation of the PI3-K pathways may be regulated by an element
      common for all three receptor types, the MyD88-IRAK-TRAF6 module being a
      candidate for this function. Using an IRAK-1-deficient cell line, we demonstrate
      that the IRAK-1-containing signaling module is essential for the IL-1-induced
      activation of the PI3-K pathway. Possible models of the interaction between IRAK
      1 and the PI3-K pathway are discussed.

PMID- 12516563
TI  - Emerging principles for the design of promiscuous HLA-DR-restricted peptides: an
      example from the major bee venom allergen.
AB  - Mechanisms underlying successful immunotherapy of allergic patients operate at
      the level of CD4+ helper T cells. T cell epitopes from allergens may thus
      constitute interesting molecules for immunotherapy, provided they are efficient
      for all patients and are not recognized by IgE. In an attempt to define such
      peptides for allergy to bee venom, we have investigated the capacity of peptides
      encompassing the sequence of the major bee venom allergen to stimulate PBMC from
      allergic patients and to react specifically with their IgE. The region 77-110
      emerged as the most frequently T cell stimulating. We then analyzed the binding
      modes of the sequence 81-97 for ten different HLA-DR molecules and introduced
      punctual mutations to enhance the peptide affinity for these molecules. Six
      different modes have been identified on the sequence 81-97, one mode being common
      to eight HLA-DR molecules. Four HLA-DR molecules can bind the P85-97 peptide by
      two different modes with an equivalent affinity. The peptide N89L has a higher
      affinity for DRB1*0301 and DRB3*0101 and remains as active as the native peptide
      towards the other HLA-DR molecules.

PMID- 12516564
TI  - Endotoxin-free heat-shock protein 70 fails to induce APC activation.
AB  - Previous work has suggested that the peptide-carrier, heat-shock protein (hsp)70,
      could directly activate APC. Here we show that this ability is related to
      endotoxin contamination of the human rhsp70 produced in Escherichia coli. Hence,
      the ability of 1-3 microg/ml of rhsp70 to induce the maturation of human monocyte
      derived DC is abrogated in the presence of the LPS-antagonist polymyxin B or when
      the rhsp70 contains less than 60 IU/mg endotoxin. Such a level of contamination
      of the rhsp70 is, however, sufficient - in the presence of soluble rCD14, the LPS
      co-receptor - to induce cytokine secretion from monocytes and DC, despite the
      presence of polymyxin B. However, when endotoxin contamination is below 10 IU/mg,
      rhsp70 does not induce cytokine secretion - even in the presence of soluble rCD14
      - or activate p38 mitogen-activated protein kinase signaling pathways, thus
      showing that an "endotoxin free" hsp70 does not activate APC.

PMID- 12516565
TI  - The route of bacterial uptake by macrophages influences the repertoire of
      epitopes presented to CD4 T cells.
AB  - We studied MHC class II (MHC-II)-restricted antigen processing of viable
      Streptococcus pyogenes by murine macrophages for presentation of two CD4 T cell
      epitopes of the surface M5 protein. We show that presentation of both epitopes
      was prevented if actin polymerization was inhibited by cytochalasin D, but not if
      clathrin-dependent receptor-mediated endocytosis was prevented, suggesting uptake
      of streptococci by phagocytosis or macropinocytosis was required for presentation
      of the surface M protein. However, treatment of macrophages with amiloride, which
      selectively blocks membrane ruffling and subsequent macropinocytosis, inhibited
      the response to one epitope (M5(308-319)), but had no effect on presentation of
      the other (M5(17-31)). The effect of the inhibitors on uptake of streptococci was
      analyzed by electron microscopy. Cytochalasin D completely blocked uptake of
      streptococci, while dimethyl-amiloride only inhibited uptake into spacious
      compartments. Neither of the inhibitors altered the cell-surface expression of
      MHC-II and costimulatory molecules analyzed by flow cytometry. The data suggest
      that distinct epitopes of a protein associated with viable bacteria may be
      presented optimally following different uptake mechanisms in the same antigen
      presenting cells.

PMID- 12516566
TI  - Different profile of CD8+ effector T cells induced in Der p 1-allergic and naive
      mice by DNA vaccination.
AB  - DNA vaccination holds great promise in both prophylactic and therapeutic
      vaccines. Recent evidence suggests that DNA vaccines could be powerful therapies
      countering Th2-mediated disorders such as allergies. Here, we studied the
      allergen-specific CD4+ and CD8+ T cell populations induced following immunization
      of allergic and non-allergic mice with DNA vaccine vectors encoding discrete
      epitopes of the house dust mite (HDM) Dermatophagoides pteronyssinus group I (Der
      p 1) allergen. Specifically, mice were sensitized to Der p 1 and exhibited a
      strong Th2/allergic response. Sensitized and non-allergic mice were then compared
      for their responses to DNA immunization. Using Elispot analysis, we demonstrate
      that allergic/vaccinated mice generate a mixed Th1/Th2 response against the
      allergen with high numbers of allergen-specific CD4+ T cells secreting IFN-gamma
      or IL-4, whereas in non-allergic/vaccinated mice a polarized Th1 response was
      dominant. Allergen-specific CD8+ T cells secreting IFN-gamma were induced at
      equal frequencies in both allergic and non-allergic mice. However, the CD8+ T
      cells from allergic mice were markedly deficient in their cytotoxic potential
      when compared to their counterparts in non-allergic mice. These results indicate
      that during an ongoing Th2 response, DNA vaccination leads to the generation of a
      distinct population of non-cytotoxic/regulatory CD8+ T cells.

PMID- 12516567
TI  - Peripheral expansion of thymus-derived regulatory cells in anti-myelin basic
      protein T cell receptor transgenic mice.
AB  - CD4+ regulatory T cells (Treg) play an indispensable role in tolerance to
      peripheral antigens, but the origin of the Treg pool in the adult remains
      unclear. Thus, while thymic commitment of Treg has been demonstrated, evidence
      also exists for the peripheral recruitment of naive tissue-specific T cells into
      Treg functions. Anti-myelin basic protein TCR transgenic mice spontaneously
      develop autoimmune encephalomyelitis when "monoclonal", but are protected by
      adoptive transfer of CD4+ cells from wild-type donors. We have now used this
      transfer system to investigate whether previously infused Treg can recruit
      transgenic T cells to regulatory functions. The results show that transgenic T
      cells from protected animals did not transfer tolerance to secondary recipients,
      and that elimination of donor Treg in protected recipients resulted in rapid
      onset of disease. In addition, Treg-containing T cell susbsets were highly
      enriched for proliferating cells in vivo, which was also the case for CD4+CD25+ T
      cells in normal animals. These observations thus exclude peripheral
      differentiation of Treg in this particular system, and indicate that expansion of
      thymically committed cells ensures the maintenance of the peripheral Treg pool in
      the adult.

PMID- 12516568
TI  - FcgammaRIIb expression on human germinal center B lymphocytes.
AB  - IgG antibody can specifically suppress the antibody response to antigen. This has
      been explained by the hypothesis that signaling through the B cell antigen
      receptor is negatively modulated by the co-ligation of immunoglobulin with the
      receptor for IgG, FcgammaRIIb. We hypothesized that inhibitory signaling through
      FcgammaRIIb would be counter-productive in germinal center cells undergoing
      selection by affinity maturation, since these cells are thought to receive a
      survival/proliferative signal by interacting with antigen displayed on follicular
      dendritic cells. We have identified and characterized a population of B
      lymphocytes with low/negative FcgammaRIIb expression that are present in human
      tonsil. Phenotypically these cells correspond to germinal center B cells and
      comprise both centroblast and centrocyte populations. In examining expression at
      the molecular level we determined that these B cells do not express detectable
      mRNA for FcgammaRIIb. We examined several culture conditions to induce expression
      of FcgammaRIIb on germinal center cells but could not determine conditions that
      altered expression. We then examined the functional consequence of cross-linking
      membrane immunoglobulin and the receptor for IgG on human B lymphocytes. Our
      results cast some doubt on the value of anti-IgG as a model for antigen-antibody
      complexes in studying human B cell regulation.

PMID- 12516569
TI  - Ephrin stimulation modulates T cell chemotaxis.
AB  - Eph receptor tyrosine kinases and their ligands, the ephrins, are known to play
      an important role in regulating cell migration and targeting in neuronal and
      endothelial cells. Recently, it has been shown that lymphoid cells also express
      Eph receptors, raising the possibility that Eph receptors may similarly regulate
      lymphocyte migration. Chemotaxis in response to soluble chemokine factors is an
      essential facet of T cell biology. We demonstrate here that T cell chemotaxis in
      response to both the stromal cell-derived factor (SDF)-1alpha and macrophage
      inflammatory protein 3beta chemokines is modulated by costimulation with ephrins.
      Both ephrin-A and ephrin-B ligands were found to modify the chemotactic responses
      of a T cell line and primary T cells. Ephrin-A1, in particular, strongly
      inhibited chemotaxis. In accordance with the tyrosine kinase activity of EphA
      receptors, ephrin-A1 stimulation induced rapid intracellular tyrosine
      phosphorylation in T cells. Although strongly inhibiting chemotaxis, ephrin-A1
      costimulus did not affect many of the signaling events downstream of the SDF
      1alpha receptor CXCR4, including calcium flux and activation of MAPK. Rather,
      ephrin-A1 altered the balance of small G protein activity in T cells. Ephrin-A1
      stimulation prevented SDF-1alpha-induced activation of cdc42, while
      simultaneously inducing rho activation. Ultimately, ephrin-A1 was found to
      inhibit chemokine-induced actin polymerization, thereby blocking migration.
      Ubiquitous ephrin expression in vivo creates enormous potential for T cells to
      encounter these ligands, suggesting that Eph receptors and ephrins may be
      important regulators of T cell migration.

PMID- 12516570
TI  - Distribution and functional analysis of memory antiviral CD8 T cell responses in
      HIV-1 and cytomegalovirus infections.
AB  - In the present study, we have investigated the anatomic distribution and the
      function of different populations of HIV-1- and cytomegalovirus (CMV)-specific
      memory CD8 T cells. The different populations of virus-specific memory CD8 T
      cells were distinguished on the basis of the expression of CD45RA and CCR7, and
      the composition of HIV-1- and CMV-specific memory CD8 T cell pools were compared
      in subjects with chronic HIV-1 and CMV co-infection. The distribution of HIV-1
      specific CD8 T cells was similar between blood and lymph node. However, CMV
      specific CD8 T cells were accumulated predominantly in the blood away from the
      lymphoid tissue. The majority (>70%) of HIV-1- and CMV-specific CD8 T cells in
      both blood and lymph node had a phenotype, e.g. CCR7-, typical of effector T
      cells. HIV-1-specific memory CD8 T cells were mostly (>80%) pre-terminally
      differentiated cells, e.g. CD45RA-CCR7-, in both blood and lymph node while 30
      50% of CMV-specific CD8 T cells were terminally differentiated, e.g. CD45RA+CCR7
      . Therefore, consistently with studies in mice, antigen-specific effector memory
      CD8 T cells accumulate predominantly in the target organ of the pathogen in
      humans, and the differences in the composition of HIV-1- and CMV-specific CD8 T
      cell pools were also present in the lymphoid tissue. A substantial proportion (30
      40%) of virus-specific CD8+CCR7+ T cells produced IFN-gamma. Thus, indicating
      that the expression of CCR7 does not provide a clear-cut separation of memory CD8
      T cells with distinct functional capacities. Taken together, these results
      provide further advances in the characterization of human memory CD8 T cells.

PMID- 12516571
TI  - An interfering form of Blimp-1 increases IgM secreting plasma cells and blocks
      maturation of peripheral B cells.
AB  - B lymphocyte-induced maturation protein-1 (Blimp-1) can drive plasmacytic
      differentiation in cultured cell models. To determine the role of Blimp-1 in B
      cell development in vivo, we have generated transgenic mice expressing an
      interfering truncated form of Blimp-1 (TBlimp) under the control of an
      immunoglobulin heavy chain promoter and intronic (E) enhancer. TBlimp-transgenic
      mice have elevated serum IgM and a prolonged IgM response. This effect is due to
      an increased number of short-lived, IgM-secreting plasma cells resulting from
      increased proliferation and prolonged survival. In addition, TBlimp-transgenic
      mice have a developmental defect in the generation of mature B cells in the
      spleen. These results show that in vivo Blimp-1 plays a fundamental role in the
      control of the life span and exit from the cell cycle of IgM secreting plasma
      cells.

PMID- 12516572
TI  - Glycosylation of type II collagen is of major importance for T cell tolerance and
      pathology in collagen-induced arthritis.
AB  - Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can
      become post-translationally modified by hydroxylation and glycosylation. T cell
      recognition of CII is essential for the development of murine collagen-induced
      arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common
      denominator of murine CIA and human RA is the presentation of an immunodominant
      CII-derived glycosylated peptide on murine Aq and human DR4 molecules,
      respectively. To investigate the importance of T cell recognition of glycosylated
      CII in CIA development after immunization with heterologous CII, we treated
      neonatal mice with different heterologous CII-peptides (non-modified,
      hydroxylated and galactosylated). Treatment with the galactosylated peptide
      (galactose at position 264) was superior in protecting mice from CIA. Protection
      was accompanied by a reduced antibody response to CII and by an impaired T cell
      response to the glycopeptide. To investigate the importance of glycopeptide
      recognition in an autologous CIA model, we treated MMC-transgenic mice, which
      express the heterologous CII epitope with a glutamic acid in position 266 in
      cartilage, with CII-peptides. Again, a strong vaccination potential of the
      glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of
      vaccination target in RA, since humans share the same epitope as the MMC mouse.

PMID- 12516574
TI  - Benign fibroepithelial breast lesion with inflammatory eosinophilic infiltration.

PMID- 12516573
TI  - Lack of deleterious somatic mutations in the CD95 gene of plasmablasts from
      systemic lupus erythematosus patients and autoantibody-producing cell lines.
AB  - The interaction of CD95 with its ligand CD95L is important for negative selection
      of B cells during the germinal center (GC) reaction. Recently, mutations
      conferring resistance to CD95-induced apoptosis have been described for human GC
      B cells. Hence, as has been demonstrated for CD95-deficient mice, also GC-derived
      autoreactive B cells carrying somatic CD95 gene mutations may potentially service
      negative selection and participate in the development of autoimmune diseases.
      Here, single plasmablasts (PB) which are implicated in the production of
      autoantibodies in systemic lupus erythematosus (SLE) patients as well as ten
      human B cell lines producing autoantibodies were analyzed for destructive somatic
      CD95 gene mutations. However, inactivating CD95 gene mutations were very rare in
      PB and not detected in the cell lines. Sequence analysis of V gene rearrangements
      amplified from single PB confirmed that the cells are (post) GC B cells and
      additionally demonstrated massive clonal expansion of these cells in two of four
      SLE patients. We conclude that CD95 gene mutations play little if any role in the
      generation of the pool of PB in SLE patients and that mutations in the CD95 gene
      are rare among autoantibody-producing B cells in SLE and rheumatoid arthritis.

PMID- 12516575
TI  - Floretlike multinucleated giant cells in a neurofibroma from a patient with NF1:
      an unusual finding for such a tumor.

PMID- 12516576
TI  - Papers from the Pediatric Restorative Dentistry Consensus Conference. San
      Antonio, Texas, April 15-16, 2002.

PMID- 12516578
TI  - An overview of hepatitis B serology screening check-up program among Thai
      workers.
AB  - In Thailand, hepatitis B virus (HBV) infection is hyperendemic; approximately 5
      million Thais are chronic HBV carriers. Here, an overview of hepatitis B serology
      among Thai workers who got the screening check-up program of King Chulalongkorn
      Memorial Hospital during January 1998 to December 2000 is reported. The data from
      hepatitis B serology examinations of 650 Thai workers who visited the Out-Patient
      Division, King Chulalongkorn Memorial Hospital during the study period for the
      screening program before starting work was analyzed. Among the subjects examined,
      107 were HBsAg-, anti-HBc-; 64 were HBsAg+, anti-HBc+; and 479 were HBsAg-, anti
      HBc+. Not unexpectedly, in the present study, the rate of chronic hepatitis B
      infection among the subjects is high (9.8%). Screening for parasitic infection
      among this population can help decrease the development of late complications as
      well as rejection of laborers by their employers.

PMID- 12516579
TI  - A note on the prevalence of anti-HIV seropositivity in the Preadmission Clinic of
      the largest Thai Red Cross Society clinic.
AB  - Clinical decision-making regarding operative procedures will be influenced when
      the patient is known to be anti-HIV, so his or her status should be discussed
      with the patient and clinician responsible for other aspects of his or her care.
      Here, we reviewed serology screening for anti-HIV in a 1-year period at the
      PreAdmission Clinic of King Chulalongkorn Memorial Hospital, the largest Thai Red
      Cross Society hospital. A total of 463 patients, 215 males and 248 females, were
      investigated, and four cases (all males) were determined to have anti-HIV
      seropositivity. The infection rate was 0.86%, similar to that of previous surveys
      of the general population. According to our study, 75% of the HIV-seropositive
      patients did not know their HIV status before our screening, and most of the
      infected cases (50%) underwent sex change surgery. The patients who underwent
      elective surgery in our clinic were usually anti-HIV seronegative. The risk group
      of our patients seems to be the sexual dysphorian patients who underwent sex
      change surgery. Additional screening tests for other infectious agents such as
      hepatitis B and hepatitis C virus is recommended. However, in a setting where HIV
      infection is common, such as in Thailand, the physician should practice universal
      precautions since any serological test poses dangers during diagnosis.

PMID- 12516580
TI  - The prevalence of hepatitis B seropositivity among patients with
      cholangiocarcinoma.
AB  - Cholangiocarcinoma is a malignancy of the biliary duct system. Presently, these
      malignant biliary tract diseases are common among the people in Southeast Asia,
      with the world's highest prevalence in northeastern Thailand and Laos. This
      carcinoma tends to grow slowly and to infiltrate the walls of the ducts,
      dissecting along tissue planes and leading to biliary tract obstruction.
      Recently, hepatitis virus-associated chronic hepatitis or cirrhosis has been
      suggested to be involved in the pathogenesis of cholangiocarcinoma. Here, we
      report the prevalence of hepatitis B seropositivity among Thai patients with
      cholangiocarcinoma. A total of 55 patients with cholangiocarcinoma, who were
      admitted to King Chulalongkorn Memorial Hospital, Thailand, during 1992-2001,
      with known hepatitis B serology was selected for further prevalence study. Of the
      55 cases (32 males and 22 females), hepatitis B seropositivity was found in five
      cases (three males and two females), giving a total prevalence rate equal to 9.1%
      (9.4% for male and 9.2% for females). Since hepatitis B infection is believed to
      be a risk factor in the development of cholangiocarcinoma, and both
      cholangiocarcinoma and hepatitis B infection are common in Thailand, screening
      and vaccination for hepatitis B may be a useful strategy to decrease the high
      rate of cholangiocarcinoma in Thailand. Further long-term study to study the
      relation of hepatitis B infection and cholangiocarcinoma is recommended.

PMID- 12516581
TI  - The rate of anti-HIV seropositivity among donated cadavers: experience in a
      cadaver donation center.
AB  - Cadavers are crucial for the medical education provided by medical schools.
      However, currently, donation is the only way to obtain cadavers for education in
      Thailand. Moreover, some traditional beliefs result in insufficient numbers of
      cadavers. Apart from finding donors, the occupational health of the workers in
      the cadaver donation center and the users, the medical students, residents, and
      staffs should be addressed. Screening for anti-HIV in donated organs is the
      current trend in transplantation medicine. Therefore, screening for anti-HIV in
      donated cadavers is useful. Here, we report the rate of anti-HIV seropositivity
      in cadavers in a 1-year period in our setting, the largest Thai Red Cross Society
      hospital. Of the total 84 cadavers received, two cadavers (2.4%) were anti-HIV
      seropositive. With the increasing rate of anti-HIV, screening for anti-HIV
      serology in donated cadavers for medical teaching is of great benefit.

PMID- 12516582
TI  - Prevalence of anti-HIV seropositivity in Myanmar migrators in a rural area of
      Thailand.
AB  - Although the prevalence of anti-HIV seropositivity in the Thai population has
      decreased in the recent years, migration of Myanmar labors as carriers into
      Thailand may increase the prevalence of anti-HIV seropositivity. Screening is
      recommended for the Myanmar migrators. Of interest, the epidemiology of anti-HIV
      seropositivity in Myanmar migrators has not been precisely determined. In this
      study, we report the prevalence of anti-HIV seropositivity in Myanmar migrators
      in a rural community in the Southern Region of Thailand with a high density of
      Myanmar migrators as fishermen. We analyzed the screening data for anti-HIV
      seropositivity among 250 Myanmar migrators (169 males and 81 females) who were in
      Thailand for less than 1 month. The anti-HIV seropositivity rate among these
      Myanmar migrants was 3.2%. The rates in males and females were 4.1% and 1.2%,
      respectively. Since these migrants can carry the disease into Thailand, screening
      tests as a prevention strategies are necessary.

PMID- 12516583
TI  - Persistent nasal ulcer.

PMID- 12516584
TI  - Working to get ephedra banned.

PMID- 12516585
TI  - Possible decompression sickness.

PMID- 12516586
TI  - Free rein for drug ads? A slowdown in FDA review has left consumers more
      vulnerable to misleading messages.

PMID- 12516587
TI  - When the test really counts: part one: earliest pregnancy detection.
AB  - We tested 18 pregnancy-test kits to find out which brands work best. Buy the top
      performers and follow our tips for the most accurate results.

PMID- 12516588
TI  - Abstracts of EUROECHO, the 6th annual meeting of the European Society of
      Cardiology Working Group on Echocardiography. Munich, Germany, 4-7 December 2002.

PMID- 12516589
TI  - When the test really counts: part two: the fertility window.
AB  - One ovulation-test kit outperformed the pack, while one performed poorly.

PMID- 12516590
TI  - Historical image. Pine-nez in case, c 1920.

PMID- 12516591
TI  - Identifying and treating substance abuse.

PMID- 12516592
TI  - Tied in knots.

PMID- 12516593
TI  - The hsj interview: Tim Kelsey. Knowledge is power. Interview by Alastair
      McLellan.

PMID- 12516594
TI  - Positive results in association studies are associated with departure from Hardy
      Weinberg equilibrium: hint for genotyping error?

PMID- 12516595
TI  - 11th Annual Research Conference and Workshop on the Pan American Health
      Organization's Centenary. November 6-8, 2002, Kingston, Jamaica. Abstracts.

PMID- 12516596
TI  - Presence of fetal DNA in maternal plasma decades after pregnancy: further
      comments.

PMID- 12516597
TI  - Back to school.
AB  - Participants on the development programme for newly appointed matrons felt they
      needed to share their experiences and develop leadership and team0building
      skills. Personality tests and receiving individual feedback were seen as helpful.
      The programme is thought to be a valuable tool in integrating these new roles in
      the trust. The matrons are now in action learning sets.

PMID- 12516598
TI  - Evidence against the long-term persistence of fetal DNA in maternal plasma after
      pregnancy.

PMID- 12516599
TI  - Historical. Apprentice samples.

PMID- 12516600
TI  - Society for Maternal-Fetal Medicine 23rd annual meeting. February 3-8, 2003. San
      Francisco, California, USA. Abstracts.

PMID- 12516601
TI  - 6th National Congress of the Italian Association of Nuclear Medicine. Genoa,
      Italy, 15-19 November 2002. Abstracts.

PMID- 12516602
TI  - Abstracts of the British Pharmacological Society Meeting. 4-6 September 2002.

PMID- 12516604
TI  - Abstracts of the 10th Annual EUPHA (European Public Health Association) Meeting.
      Bridging the gap between research and policy in public health: information,
      promotion and training. Dresden, Germany, 28-30 November 2002.

PMID- 12516603
TI  - Prevention of catheter-related sepsis in HPN.

PMID- 12516605
TI  - Abstracts of the Nutrition Society meetings. March 2002, June 2002, July 2002.

PMID- 12516606
TI  - Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa:
      common pathogenesis with Barrett's adenocarcinoma?
AB  - Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa is a
      rare tumor, with only 15 cases reported to date. We report a case in a 61-year
      old man complaining of dysphagia. The upper endoscopy revealed that the tumor
      measured 3 cm and was 22 cm distant from the incisivors. A hiatal hernia with
      erosive esophagitis of the distal esophagus was present. On microscopic
      examination the tumor corresponded to a poorly differentiated adenocarcinoma
      immunoreactive for cytokeratin (CK) 7 and p53. The surrounding heterotopic
      gastric mucosa contained foci of intestinal metaplasia immunoreactive for CK7 in
      the surface epithelium and the entire glands and CK20 in the superficial
      epithelium and superficial glands. The CK7 and p53 positivity that we observed is
      very common in Barrett's adenocarcinomas. Moreover, intestinal metaplasia in
      heterotopic gastric mucosa shows the same CK7/CK20 pattern as specialized
      Barrett's mucosa. These common features shared by adenocarcinomas of the upper
      esophagus arising in heterotopic gastric mucosa and adenocarcinoma of the lower
      esophagus developing on Barrett's mucosa suggest that those two types of cancer
      have a common pathogenesis, related to gastroesophageal reflux disease.

PMID- 12516608
TI  - Abstracts from the 33rd annual meeting of the American Association for Hand
      Surgery. Kauai, Hawaii, January 8-11, 2003.

PMID- 12516607
TI  - Micropapillary bladder carcinoma.

PMID- 12516610
TI  - Indian endocrinologists warn of vitamin D deficiency.

PMID- 12516611
TI  - Tel Aviv hospital destroys frozen embryos by mistake.

PMID- 12516612
TI  - Inadequate research facilities fail to tackle mystery disease.

PMID- 12516614
TI  - Scottish postoperative care is improving.

PMID- 12516613
TI  - Genetic relationships among some tribal groups inhabiting the north-eastern,
      eastern and sub-Himalayan regions of India.
AB  - The origins and genomic affinities of various tribal populations of India are of
      considerable contemporary interest. In this study, we have investigated
      relationships among five tribal groups inhabiting the north-eastern, eastern and
      sub-Himalayan regions of India. DNA samples have been analysed in respect of 25
      polymorphic loci, based on which genetic affinities have been estimated. The
      interesting findings of this study are (i) the Tibeto-Burman speaking,
      morphologically Mongoloid, tribal groups of India are not genetically very
      homogeneous, and (ii) the Tharu, a group inhabiting the sub-Himalayan region, may
      indeed have undergone considerable admixture as has been postulated by some
      anthropologists.

PMID- 12516615
TI  - Haplotype analysis and phylogeny of ornithine transcarbamylase polymorphisms.
AB  - Ornithine transcarbamylase (OT2, EC 2.1.3.3) deficiency, the most common inborn
      error of urea cycle, is caused by a vast number of point mutations, deletions and
      insertions in the respective gene. Furthermore, 12 single nucleotide
      polymorphisms (NSPs) have been described in the OTC gene, four of them causing an
      amino acid change. We have studied the frequency of these markers in two
      populations: Portuguese and Mozambican. No significant differences were observed
      between populations, except for Lys --> Arg in codon 46. Allelic associations
      between polymorphisms were used to define haplotypic patterns. The three common
      haplotypes (H1, H2 and H3) show a combined frequency of 95% in Portugal and 87%
      in Mozambique. One haplotype was found only in Portugal and three are only
      present in Mozambique, resulting in a higher haplotype diversity. The combined
      information from the SNPs and the DXS1068 (CA)n repeat was used to outline OTC
      haplotype phylogeny, which, in conjunction with the population data, allowed us
      to sketch possible evolutionary pathways although some haplotypes could have
      arisen by either repeated mutation or recombination.

PMID- 12516616
TI  - European Association of Cardiothoracic Anaesthesiologists 17th annual meeting.
      Dublin, Ireland, June 12-15, 2002. Abstracts.

PMID- 12516617
TI  - Commentary: a "good death" is possible in the NHS.

PMID- 12516618
TI  - Recommendations for the reporting of lymphoid neoplasms: a report form the
      Association of Directors of Anatomic and Surgical Pathology.

PMID- 12516619
TI  - 11th Asian Australasian Congress of Anaesthesiologists (AACA). 10-13 July 2002.
      Abstracts.

PMID- 12516620
TI  - Nurses really do need to support each other.

PMID- 12516622
TI  - [Argentine Society of Clinical Investigation XLVII Meeting and Argentine Society
      of Immunology L Meeting. 20-23 November 2002. Abstracts].

PMID- 12516621
TI  - Nurse lecturers are needed on the wards.

PMID- 12516623
TI  - Public autopsies could be an educational tool.

PMID- 12516624
TI  - NHS pay deal demand nurses expand their roles.

PMID- 12516625
TI  - Misconduct case shows ageist attitudes.

PMID- 12516626
TI  - Does nursing need a definition of its role.

PMID- 12516628
TI  - AHCA 2002 Quality Award winners. Step 2 winners make quality a mission.

PMID- 12516627
TI  - Does nursing need a definition of its role.

PMID- 12516629
TI  - IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity
      of decidual lymphocytes.
AB  - PROBLEM: Perforin expressing uterine natural killer (uNK) cells are under complex
      cytokine influence. The aim of the study was to investigate the presence and role
      of interleukin (IL)-18 on NK cytolytic potential at maternal-fetal (M-F)
      interface. METHOD OF STUDY: Peripheral blood cells and decidual tissue were
      obtained from elective pregnancy termination of normal human 6-10-week-old
      pregnancies. Perforin expression and cytolytic activity of peripheral blood (PBL)
      and decidual lymphocytes (DL) were analyzed by flow cytometry. IL-18 positive
      decidual adherent cells (DAC) were detected by the same method. Interleukin-18
      and IL-18 receptor (IL-18R) expression on the trophoblastic cells was detected by
      immunohistology using biotinylated anti-IL-18 and IL-18R monoclonal antibodies.
      RESULTS: The IL-18 added in a dose of 10 ng/mL up-regulates perforin expression
      and cytolytic activity of DL. Simultaneous stimulation with IL-18 and IL-12
      enhanced DL cytolytic activity, while IL-18 combined with IL-10 or IL-15 did not
      show this effect. Cytolytic activity of PBL was up-regulated by IL-18 as well,
      and this effect was enhanced by the addition of IL-12 and IL-15. Interleukin-18
      did not affect perforin-protein expression in cultured PBL. Approximately 20% of
      DAC were IL-18 positive and these cells were mostly human leukocyte antigen (HLA)
      DR negative. IL-18R positive cells were found on syncytiotrophoblast cell layer,
      interstitial tissue cells of villi and fetal blood cells. There was no detectable
      IL-18 staining on trophoblast cell layer on villi, but strong staining of fetal
      blood cells in villous vessels. CONCLUSION: These are first results showing IL
      18R expression, but not IL-18 expression on villous trophoblastic cells, as well
      as enhancement of perforin expression and NK cytolytic potential of DL under the
      influence of IL-18. IL-18 in concert with other cytokines and hormones could play
      an important role in the regulation of cytolytic potential of first trimester
      pregnancy decidual and peripheral blood NK cells.

PMID- 12516630
TI  - Progesterone induced blocking factor (PIBF) mediates progesterone induced
      suppression of decidual lymphocyte cytotoxicity.
AB  - PROBLEM: Progesterone induced blocking factor (PIBF) is a mediator of
      progesterone that blocks peripheral blood lytic natural killer (NK) activity.
      Progesterone or PIBF stimulated decidual macrophages block up-regulation of
      perforin expression in decidual lymphocytes (DL). Therefore, we investigated
      whether progesterone regulates cytotoxicity of DL. METHOD OD STUDY: Decidual
      mononuclear cells were cultured with progesterone. PIBF, progesterone and anti
      PIBF antibody or in the medium only. Cytolytic activity of non-adherent DL was
      measured by PKH-26 (red) 2 hr cytolytic assay and flow cytometry. Perforin
      positive DL were detected by immunofluorescency and PIBF-positive cells by
      immunohistology. RESULTS: Progesterone and PIBF, in a dose-dependent manner
      decreased cytotoxicity of DL against K-562 targets, and perforin egzocytosys was
      blocked. Anti-PIBF antibodies reversed the progesterone mediated reduction in
      cytolytic activity of DL. PIBF positive cells were found in first trimester
      pregnancy decidua. CONCLUSION: The results indicate possible role for PIBF, as a
      mediator of progesterone in regulation of DL cytolytic activity at the maternal
      foetal (M-F) interface.

PMID- 12516631
TI  - Regulation of trophoblast invasion by IL-1beta and TGF-beta1.
AB  - PROBLEM: To investigate the effect of IL-1beta and TGF-beta1 on trophoblast
      derived proteases and their inhibitors at the mRNA and protein level for
      elucidation of the mechanism of trophoblast invasion. METHOD OF STUDY:
      Trophoblast derived proteases and their inhibitors were localized in human
      placental villi by immunohistochemistry, their regulation at mRNA and protein
      levels were studied using RT-PCR and zymography, respectively, on trophoblast
      cells in culture. RESULTS: Trophoblast proteases, matrix metalloproteases (MMP-2,
      MMP-9), membrane type matrix metalloproteases (MT-MMP1 & 2) and urokinase type
      plasminogen activator (uPA) were found to be up regulated by IL-1beta while the
      protease inhibitors, tissue inhibitor of metalloproteases (TIMP-1 & 2) and
      plasminogen activator inhibitors (PAI-1 & 2) to be up regulated by TGF-beta1.
      CONCLUSION: Temporo-spatial regulation of trophoblast invasion is the outcome of
      a balanced interplay between the proteases and their cognate inhibitors. IL-1beta
      and TGF-beta1 seem to be critical for regulating the protease network thereby
      effectively controlling the extent to which the trophoblast may invade the
      maternal endometrium.

PMID- 12516632
TI  - Heat shock fusion protein gp96-Ig mediates strong CD8 CTL expansion in vivo.
AB  - PROBLEM: As shown previously, gp96-Ig peptide complexes secreted by an ovalbumin
      transfected tumor (EG7) mediate strong, specific tumor immunity through a CD4 T
      cell independent CD8+ CTL response. In this study, we set out to develop a system
      to quantitatively determine the CD8 CTL response to gp96-Ig and to evaluate the
      influence of an established wild type tumor. METHODS: Secreted heat shock protein
      gp96-Ig was constructed by replacement of the endoplasmic reticulum retention
      signal with the Fc portion of IgGI, transfected into EG7 (EG7-gp96-Ig) and used
      to induce CD8+ CTL expansion in vivo. Adoptively transferred, ovalbumin specific
      T-cell receptor (TCR) transgenic CD8+ cells (OT-1) responded with clonal
      expansion to the immunization with EG7-gp96-Ig. OT-1 expansion was quantitated
      with K(b-peptide)-tetramers by flow cytometry. RESULTS: In response to primary
      immunization with EG7-gp96-Ig, OT-1 expand from an initial frequency of 0.5 to
      25% of all CD8 cells, and to 50% of all CD8 cells after a booster immunization.
      Endogenous ovalbumin specific CD8 cells also expand strongly. Antigen specific
      effector function was measured by enzyme-linked immunosorbent spot-forming cell
      assay (ELISPOT) for interferon-gamma (IFN-gamma). While effector function was
      strongly induced by secreted gp96-Ig, not all expanded OT-1 produce IFN-gamma.
      EG7 does not cause OT-1 expansion, but rather induces anergy. If OT-1 are
      transferred into wild type EG7 tumor bearing mice to induce anergy of OT-1,
      immunization with EG7-gp96-Ig can partly overcome unresponsiveness. CONCLUSIONS:
      We conclude that secreted gp96-Ig is a powerful mediator of specific CD8+ CTL
      responses in vivo. Secretory gp96 mimics release of gp96 by damaged or necrotic
      cells that is able to activate dendritic cells without CD4 help. Gp96-Ig
      associated peptides have not been selected by binding to major histocompatibility
      complex (MHC). Specific immunization by secreted gp96-Ig therefore is expected to
      occur also in allogeneic settings.

PMID- 12516633
TI  - Expression of functional Fas ligand in choriocarcinoma.
AB  - PROBLEM: In the course of pregnancy, fetal trophoblast cells and in that of
      choriocarcinoma-etiology, trophoblast derived tumor cells, invade the uterine
      mucosa without causing rejection by decidual leukocytes. Fas ligand (FasL, CD95L,
      APO-IL), a central regulator of the immune system, has been implicated in the
      maintenance of immune privileged sites, such as the eye, the testis and the
      pregnant uterus by inducing apoptosis in activated infiltrating leukocytes. In
      normal pregnancy FasL, which is expressed by trophoblast cells, appears to
      contribute to the immune privilege of the pregnant uterus. As choriocarcinoma
      derives from trophoblast we wanted to assess the expression of FasL in this
      tissue. METHOD OF STUDY: Immunohistochemistry, immunofluorescence, TUNEL-assay,
      Western blotting, coculture experiments and flourescence-associated cell sorter
      analysis were the techniques used. RESULTS: Expression of FasL was found on cells
      of choriocarcinoma in paraffin sections in situ and on three choriocarcinoma cell
      lines such as JEG-3, JAR and BeWo. These results were confirmed by Western
      blotting. In coculture experiments choriocarcinoma cells induced apoptosis in a
      Jurkat cell line - sensitive to FasL mediated killing. However, when the Jurkat
      cells were pre-incubated with a Fas-blocking monoclonal antibody, apoptosis was
      abolished to a great extent. CONCLUSION: Our findings show that choriocarcinoma
      cells express FasL and this aforementioned molecule is biologically active. We
      assume that FasL expression on choriocarcinoma cells may contribute to control of
      anti-tumor responses by inducing apoptosis in activated Fas bearing leukocytes.

PMID- 12516634
TI  - The role of pro- and anti-apoptotic molecular interactions in embryonic
      maldevelopment.
AB  - PROBLEM: Pregnancy loss and the occurrence of inborn structural anomalies are
      often preceded by excessive apoptosis in targeted embryonic and extraembryonic
      tissues. Apoptogenic stimuli activate both death and survival, signaling cascades
      consisting of molecules acting as activators and effectors, or negative
      regulators of apoptosis. The interplay between these cascades determines whether
      the cell which is exposed to an apoptogenic stimulus dies or survives. This
      review summarizes the functioning of pro- and anti-apoptotic molecules in embryos
      responding to various teratogens. The effect of potentiation of the maternal
      immune system on these molecules is also discussed. METHODS OF STUDY: The data on
      the functioning of various pro- and anti-apoptotic molecules in embryos exposed
      to various developmental toxicants, and embryos developing in a diabetic
      environment are reviewed. Techniques such as the TUNEL method, DNA fragmentation
      assay, electromobility shift assay (EMSA), fluorometric assay,
      immunohistochemistry, Western blot, In situ hybridization, have been used in our
      studies to detect apoptosis, and evaluate the functioning of molecules such as
      TNFalpha, caspases, NF-kappaB and IkappaB, p53, and bcl-2 in different embryonic
      and extraembryonic tissues. RESULTS: Our and other data summarized in this review
      have demonstrated that the doses of developmental toxicants required to induce
      pregnancy loss and gross structural anomalies induce excessive apoptosis shortly
      after treatment. Depending on the intensity and type of targeted tissues, this
      apoptosis was accompanied by alterations in the activity of the molecules which
      act as activators and effectors (e.g. caspase 3, caspase 8, caspase 2, p53) or
      negative regulators (bcl-2, NF-kappaB) of apoptosis. Maternal immunopotentiation,
      which decreases the level of induced and spontaneous pregnancy loss and the
      incidence and severity of teratogen-induced structural anomalies has been shown
      to modulate the expression of these molecules both in embryonic tissues and at
      the feto-maternal interface. CONCLUSIONS: The data presented in this review
      suggest that molecules such as TNFalpha, caspase 3, caspase 8, NF-kappaB, p53 and
      bcl-2, which are involved in the regulation of apoptosis, may also be involved in
      determining the sensitivity of the embryo to developmental toxicants. Maternal
      immunopotentiation may modulate the functioning of these molecules.

PMID- 12516635
TI  - Questioning the Th1/Th2 paradigm in reproduction: peripheral levels of IL-12 are
      down-regulated in miscarriage patients.
AB  - PROBLEM: It has been postulated that a T helper (Th)1 response is associated with
      pregnancy failure, whereas a Th2 response contributes to pregnancy maintenance.
      However, this Thl/Th2 dichotomy has recently been hypothesized to be an
      oversimplification. To prove this novel hypothesis, we investigated the levels of
      the Th1-inducer cytokine interleukin (IL)-12 in immunocompetent cells of patients
      with normal pregnancies (NP) and spontaneous abortion (SA). METHODS: Presence of
      intracellular IL-12 was evaluated in CD8+ and CD56-blood and decidual lymphocytes
      as well as in monocytes and granulocytes by flow cytometry from NP and SA
      individuals. IL-12 serum levels were measured by enzyme-linked immunosorbent
      assay (ELISA). We further investigated the effect of recombinant human (rh) IL-12
      on the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha
      in peripheral leukocytes ex vivo. RESULTS: In patients suffering from SA we
      observed lower percentages of IL-12 in lymphocytes, monocytes and granulocytes
      derived from peripheral blood and decidua, compared with women with normally
      progressing pregnancies. No differences could be observed when evaluating the
      levels of IL-12 in the granulocyte population. The IL-12 serum levels were below
      the ELISA sensitivity limit. Ex vivo stimulation of the peripheral blood cells
      with increasing doses of IL-12 resulted in a significant decrease of IFN-gamma+,
      whereas levels of TNF-alpha+ in lymphocytes were unaffected. CONCLUSIONS: The
      classical Th1/Th2 paradigm appears to be insufficient to exclusively explain the
      causes of pregnancy loss. Our current results render us to requestion the role of
      Th1 cytokines during pregnancy and suggest some protective function of the Th1
      inducer cytokine IL-12.

PMID- 12516636
TI  - Some thoughts on the reproductive autoimmune failure syndrome (RAFS) and Th-1
      versus Th-2 immune responses.
AB  - PROBLEM: The concept of immunologically induced reproductive failure has remained
      very controversial. Especially the question whether abnormal immune function can
      cause infertility has recently been subject to strong disagreement. This opinion
      piece is an attempt to reconcile difference of opinion by integrating clinical
      data from the human experience with well-established experimental models in
      animals. METHOD OF STUDY: Review of published literature. RESULTS: Experimental
      animal data, especially in the mouse, have suggested that normal pregnancy
      requires a switch to an immune response with T helper (Th)-2 preponderance.
      Recent data from the human experience suggest that infertility, repeated
      pregnancy loss and certain complications of pregnancy may be the consequence of
      abnormal Th-1 preponderance. In analogy, to animal models, immunologic
      reproductive failure in humans, may therefore not be the consequence of specific
      autoantibody abnormalities or natural killer (NK)-cell abnormalities, but the
      reflection of a misdirection of a more broadly based immune response.
      CONCLUSIONS: Under such a model, both diagnosis and treatment of immunologically
      induced forms of reproductive failure require re-evaluation. Such a model,
      however, provides a satisfactory explanation for contradictory findings in the
      human experience that have led to strong disagreements among investigations.

PMID- 12516637
TI  - Relationship between ovarian stimulation regimen and interleukin level in pre
      ovulatory follicular fluid and their effect on ICSI outcome.
AB  - PROBLEM: The aims of this study were (i) to identify the presence and
      concentration of interleukin-6 (IL-6), IL-8 and granulocyte-macrophage colony
      stimulating factor (GM-CSF) in pre-ovulatory follicular fluid (FF) in patients
      undergoing controlled ovarian hyperstimulation regimen for intracytoplasmic sperm
      injection (ICSI) with recombinant human follicle stimulating hormone (rFSH)
      (G.1), hMG (G.2) or rFSH/ hMG (G.3) treatment and (ii) to determine whether
      controlled ovarian hyperstimulation stimulation regimen could affect the
      concentration of these investigated interleukins and as a consequences the ICSI
      outcome. (iii) Moreover, it was intended to clarify the association between these
      investigated parameters and the peripheral blood level of estradiol 17-beta,
      progesterone, leuteinizing hormone (LH) at the day of oocyte retrieval and (iv)
      finally to find out whether these interleukin concentrations in FF could be
      considered as an additional parameter for predicting fertilization and pregnancy
      outcome in ICSI patients. MATERIAL AND METHODS: Interleukin-6, IL-8 and GM-CSF
      concentrations were determined in the FF of 85 patients. The levels of these
      interleukins were measured by the enzyme-linked immunosorbent assay (ELISA)
      technique, using commercially available kits. RESULTS: Interleukin-6 (6.5 +/- 4.6
      pg/mL), IL-8 (222.9 +/- 163.4 pg/mL) and GM-CSF (1.6 +/- 2.7 pg/mL) were present
      in pre-ovulatory FF in ICSI patients. No significant difference in the mean
      concentration of IL-6, IL-8 and GM-CSF was found between the groups. Moreover,
      there was no correlation between these interleukin levels in FF and steroid
      hormone concentration in the peripheral blood. CONCLUSIONS: Interleukin-6, IL-8
      and GM-CSF were found in FF of patients undergoing ovarian hyperstimulation for
      ICSI treatment. The stimulation protocols showed no influence on these
      interleukin levels in FF. Moreover, no correlation was found between these
      investigated interleukins and steroid hormone concentrations in peripheral blood
      or ICSI outcome. Therefore, the determination of interleukin level in FF of
      patients undergoing ovarian hyperstimulation for ICSI therapy could not be
      recommended as a prognostic factor for ICSI outcome.

PMID- 12516638
TI  - Antiphospholipid antibody round table report.

PMID- 12516639
TI  - Recurrent reproductive wastage and immunologic factors.
AB  - PROBLEM: The causes of recurrent reproductive wastage are varied and complex. The
      present study was designed to focus on the role of immunologic factors in cases
      where other causes were not evident. METHOD OF STUDY: Over 20 years, more than
      1500 couples were evaluated in our clinic because of recurrent spontaneous
      abortion. Women were tested for anti-phospholipid antibodies and plasma contact
      proteins of the intrinsic pathway of blood coagulation after endocrine, organic,
      infectious and genetic etiologies of miscarriages were excluded. RESULTS: Anti
      phosphatidylethanolamine antibodies, anti-annexin antibodies, and factor XII
      deficiency were more common factors in recurrent spontaneous abortion patients
      than were anti-cardiolipin antibodies in terms of induction of recurrent
      pregnancy losses. Paternal leukocyte immunotherapy of patients without such
      abnormalities was associated with a significantly improved success rate.
      CONCLUSIONS: Recurrent reproductive wastage can be minimized by individualized
      therapy based on comprehensive evaluation of immunologic factors, including
      several anti-phospholipid antibodies.

PMID- 12516640
TI  - Antibody-binding proteins in human seminal plasma.
AB  - PROBLEM: The significance of antibody-mediated infertility is unclear and
      complicated by the finding of that antisperm antibodies are found both in fertile
      and infertile couples. Seminal plasma contains immunosuppressive factors, one
      such factor may be antibody-binding proteins (ABP's). METHOD OF STUDY: Antibody
      binding-proteins were purified using human IgG or IgG-Fc affinity chromatography
      columns. The purified antibody-binding proteins were characterized by their
      molecular weights, partial amino acid sequences, and immunoreactivities. RESULTS:
      Three proteins of molecular weight 74, 70 and 55 kDa and other low molecular
      weight proteins specifically bound to the IgG or IgG-Fc affinity columns
      demonstrating Fc-binding specificities. These proteins were not FcgammaRIII, IgG,
      or fragments of these proteins by their behaviors under reducing conditions,
      Western blot, and partial amino acid sequence analyses. Amino acid sequence data
      demonstrated some of these proteins to be novel. CONCLUSIONS: We have isolated
      and partially characterized several ABP's from seminal plasma. The IgG-binding
      proteins we have identified may protect spermatozoa against antibody-mediated
      damage by conferring protection to antibody-coated spermatozoa. If this
      hypothesis holds true, differences in the level or function of these ABP's may
      alter the status of fertility.

PMID- 12516641
TI  - Interleukin regulation of asymmetric antibody synthesized by isolated placental B
      cells.
AB  - PROBLEM: Protecting antibodies against trophoblast surface molecules were
      previously described. Here we analysed the synthesis of asymmetric IgG by
      placental B-lymphocytes. METHOD OF STUDY: B cells were isolated from human term
      placenta and cord blood, stimulated with anti-CD40 IgG and cocultured with
      transfected Fcgamma R-expressing mice Ltk-fibroblast. Interleukin-4, IL-6, IL-10,
      IL-11 and IL-13 were added to cultures for 14 days. Asymmetric IgG were assessed
      in culture supernatants by concanavalin A (Con A) fixation and enzyme-linked
      immunosorbent assay. RESULTS: When IL-6 was added to the cultures, the
      percentages of asymmetric IgG synthesized by placental B cells were: IL-6: 29 +/-
      10; IL-6 + IL-10: 24 +/- 7; IL-4 + IL-10 + IL-6: 38 +/- 9. The last combination
      induced the highest increase in the asymmetric IgG synthesis as compared with
      control (19 +/- 10%, P < 0.05). Additionally, placental B cells synthesized more
      asymmetric IgG than umbilical cord blood B-lymphocytes (P = 0.0015). CONCLUSIONS:
      Isolated placental B-lymphocytes synthesized asymmetric IgG in response to Th2
      interleukins, more notably IL-6 in combination with IL-4 and IL-10. The in vitro
      increase of protective asymmetric IgG synthesis in response to Th2-cytokines
      support the hypothesis that a local Th2-switch is beneficial for pregnancy
      outcome.

PMID- 12516642
TI  - Characterization of proteins from boar prostate.
AB  - PROBLEM: Most components of seminal plasma are secreted by accessory sexual
      glands: seminal vesicle, prostate gland and bulbourethral gland. The portion of
      proteins secreted by prostate gland differs in various species. Characterization
      of boar prostate proteins is the subject of this communication. METHODS OF STUDY:
      Proteins of boar prostate gland were separated by affinity chromatography on
      heparin-polyacrylamide to non-heparin-binding (H-) and heparin-binding (H+)
      fractions. The H- and H+ fractions were subjected to reverse phase high
      performance liquid chromatography (RP HPLC) and their elution profiles were
      compared with those of the H- and H+ fractions of boar seminal plasma. The
      isolated proteins were characterized by sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE), immunodetection, N-terminal amino acid sequencing
      and mass spectrometry (MALDI). RESULTS: The following proteins of boar prostate
      secretion were identified: beta-microseminoprotein, serotransferrin, serum
      albumin, myoglobin and PSP I and PSP II spermadhesins. CONCLUSION: Presented
      results demonstrate composition of the main proteins of boar prostate secretion.
      Beta-Microseminoprotein was found to be a major protein of prostate secretion.
      PSP I and PSP II, major proteins of the H- fraction of boar seminal plasma, were
      found in boar prostate secretion in lower amounts. The major proteins of the H+
      fraction of boar seminal plasma (AQN, AWN) were not detected in prostate
      secretion.

PMID- 12516643
TI  - Nonsubmerged and submerged implants in the treatment of the partially edentulous
      maxilla.
AB  - BACKGROUND: Dental implants vary in design and surfaces. In addition, different
      surgical techniques have been used for implant insertion. The ITI Dental Implant
      System (Straumann AG, Waldenburg, Switzerland) has always required a one-stage
      technique, whereas the Branemark System (Nobel Biocare AB, Gothenburg, Sweden)
      requires a two-stage technique. PURPOSE: The aim of this study is to compare the
      outcome of fixed partial bridges in the maxilla supported by both ITI and
      Branemark implants in a split-mouth design. MATERIALS AND METHODS: Twenty-eight
      patients with a residual anterior dentition in the maxilla were included in this
      split-mouth study. The Branemark implants were used on one side and the ITI
      implants on the other side of the residual dentition according to a randomization
      procedure. A blocking size of four was used, giving equal probability of placing
      ITI or Branemark implants in the right or left side of the jaw. The surgical and
      prosthetic procedures followed the guidelines given by the manufacturers. The
      prosthetic treatment with the two-implant systems was performed at the same time,
      and for that reason the healing period was 6 months for both systems. The
      observation period for all patients was 1 year after loading. RESULTS: Two
      Branemark implants (in one patient) were lost before loading, and one ITI implant
      was lost 1 year after loading. There was no significant difference in survival
      rate. Radiographic examination of the bone level was performed at the time of
      delivery of the bridge and after 1 year. The mean marginal bone level at baseline
      was situated 1.9 mm from the reference point for the Branemark implants and 1.5
      mm for the ITI implants. With regard to the insertion depth used, these bone
      levels indicate that bone loss had taken place before baseline. However, between
      baseline and the 1-year examination, there was no significant change of the
      marginal bone (0.2 +/- 0.08 mm at the Branemark implants and 0.1 +/- 0.11 mm at
      the ITI implants). The difference between results with the two implants was not
      statistically significant. Crater-form bone destructions were seen at some ITI
      implants, indicating periimplantitis. However, at only two implants were there
      clinical signs of periimplantitis. CONCLUSIONS: No significant difference in
      survival rate or in marginal bone change could be demonstrated between the two
      systems. At some ITI implants (18%), crater-form bone loss was observed.

PMID- 12516644
TI  - Stability measurements of osseointegrated implants using Osstell in partially
      edentulous jaws after 1 year of loading: a pilot study.
AB  - BACKGROUND: The introduction of resonance frequency analysis (RFA) as a
      commercially available technique has made it possible to measure implant
      stability in implant stability quotient (ISQ) units at any time during the course
      of implant treatment and loading. However, no information on normal ISQ levels
      can be found in the literature. PURPOSE: The aim of this pilot study was to
      measure the stability of clinically successful implants in partially edentulous
      patients after 1 year of loading and to study the influence of jaw,
      anterior/posterior position, implant length, and marginal bone level on implant
      stability. MATERIALS AND METHODS: Fourteen partially edentulous patients
      previously treated with 45 implants were subjected to clinical and radiographic
      evaluations and RFA measurements using Osstell (Integration Diagnostics,
      Savedalen, Sweden) after 1 year of loading. RESULTS: All 45 implants were stable,
      and implant stability levels were in the range of 57 to 82 ISQ units with a mean
      of 69 +/- 6.5 ISQ after 1 year of loading. Mandibular implants were more stable
      than were maxillary ones. There were no differences between anterior and
      posterior implants. No correlation could be found between implant length and
      stability. Only minor marginal bone resorption was observed. CONCLUSIONS: The
      results from this limited material showed that successfully integrated implants
      have ISQ levels from 57 to 82 ISQ with a mean of 69 ISQ after 1 year of loading.
      Mandibular implants are more stable than are maxillary ones. High implant
      stability can be achieved with short implants and placement in posterior regions.

PMID- 12516645
TI  - Early loading of four or five Astra Tech fixtures with a fixed cross-arch
      restoration in the mandible.
AB  - BACKGROUND: A change in implant placement has emerged recently from two-stage to
      one-stage surgery and to earlier and even immediate loading of the fixtures.
      PURPOSE: The aim of this study was to verify whether four or five fixtures
      installed in the edentulous mandible were suitable for early loading with a cross
      arch fixed restoration. MATERIALS AND METHODS: In 25 consecutively treated
      patients (28-88 yr), four or five Astra Tech fixtures (Molndal, Sweden) were
      installed in edentulous mandibles. During the same surgical procedure, the
      abutments were connected. An impression was taken immediately after surgery. All
      patients received a fixed prosthetic rehabilitation of 10 to 12 teeth made of a
      cast metal framework and acrylic teeth/gingiva within a month. The fixtures were
      followed up clinically and radiographically for 7 to 24 months. Bone level was
      measured from the most coronal point of the vertical part of the fixture to the
      most apical bone level mesially or distally. RESULTS: No fixtures were lost
      during follow-up. No postoperative complications occurred. Radiographic analysis
      showed a mean bone level of 0.6 mm after 7 to 12 months. Fixtures followed up
      from 13 to 18 and 19 to 24 months showed a mean bone level of 0.7 mm. Around two
      fixtures, the bone level was found at the first implant thread. All other
      fixtures showed the bone level somewhere along the vertical unthreaded part of
      the fixture. CONCLUSIONS: Early loading within 1 month of four or five Astra Tech
      fixtures in the edentulous mandible is a predictable procedure for a follow-up
      period of 6 to 24 months.

PMID- 12516646
TI  - Early loading of machined-surface Branemark implants in completely edentulous
      mandibles: healed bone versus fresh extraction sites.
AB  - BACKGROUND: Restoration of edentulous mandibles with dental implants installed
      with a two-stage or one-stage surgical approach, yet with delayed loading, is a
      predictable and successful treatment. PURPOSE: The present prospective study
      evaluated the success up to 3 years of function of nonroughened machined-surface
      Branemark System implants (Nobel Biocare AB, Gothenburg, Sweden) loaded early or
      immediately with a fixed 12-unit bridge. MATERIALS AND METHODS: In total, 184
      implants were installed in 36 patients: 30 with healed bone and 6 with some
      remaining teeth, which were extracted simultaneously with implant installation.
      The provisional or final prostheses were installed 0 to 52 (mean 18.2) days
      later. RESULTS: Thirteen of 184 (7.1%) implants failed within 3 months of loading
      in 5 of 36 (13.9%) patients: 1 of 153 implants (0.7%) failed in healed bone, and
      12 of 31 (39%) failed in fresh extraction sites. This consequently meant a loss
      of 3 of 36 (8.3%) prostheses, all in the extraction group. No implants were lost
      during 3 years of functional loading (16 patients, 75 implants). The average
      marginal bone level measured initially and after 1, 2, and 3 years was 0.8 mm (SD
      = 0.5), 1.0 mm (SD = 0.4), 1.1 mm (SD = 0.3), and 1.4 mm (SD = 0.5),
      respectively. CONCLUSIONS: Four to six Branemark implants with nonroughened
      machined titanium surfaces can be loaded early or immediately with cross-arch
      restorations in healed mandibulary bone, but this cannot be recommended for fresh
      extraction sites.

PMID- 12516647
TI  - Effect of barrier membranes and autologous bone grafts on ridge width
      preservation around implants.
AB  - BACKGROUND: The purpose of this study was to explore the effect of barrier
      membranes and autologous bone grafts on the preservation of ridge width around
      implants. MATERIALS AND METHODS: Sixty-one patients were chosen from a database
      of case series; treatment assignment was based on clinical judgment. The patients
      received a total of 76 implants: 34 implants with guided tissue regeneration
      procedures, 27 with autologous bone grafts, and 15 without ridge preservation
      procedures (control group). RESULTS: The ridge width around the 76 implants
      decreased an average of 1.4 mm (95% CI, -1.9 to -1.1 mm). Implants placed with
      autologous bone grafts or membranes tended to have worse outcomes. When compared
      to the no augmentation group, implants placed with guided tissue regeneration and
      autologous bone grafts resulted in 0.1 mm of additional bone loss (95% CI, -1.7
      to -1.5 mm; p < .93) and 0.8 mm of additional bone loss (95% CI, -2.3 to 0.7 mm;
      p < .28), respectively. CONCLUSIONS: Autologous graft procedures or barrier
      membranes do not appear to improve crestal ridge preservation around implants.

PMID- 12516648
TI  - Reconstruction of the anterior maxilla with platelet gel, autogenous bone, and
      titanium mesh: a case report.
AB  - BACKGROUND: Reconstruction of defects in the anterior part of the maxilla to
      enable implant placement is a challenging treatment. Recent studies have
      suggested that the use of autogenous platelet gel may contribute to improved
      healing of bone grafts. PURPOSE: A case is presented in which particulated
      autogenous bone, platelet gel, and a titanium mesh were used for alveolar bone
      reconstruction of the anterior maxilla prior to implant placement. MATERIALS AND
      METHODS: Corticocancellous bone from the iliac crest was mixed with a preparation
      of autogenous platelet gel (platelet-rich plasma, thrombin, and calcium chloride)
      and placed against a titanium mesh fixed to the bone of the palate in a patient
      with severe resorption of the anterior maxilla. After 4.5 months of healing the
      mesh was removed and titanium implants were placed. A prolonged healing period of
      8 months was allowed before healing abutments were placed and a fixed dental
      bridge was fabricated. RESULTS: Healing was uneventful, and the anterior maxilla
      had increased in height and width during the initial healing. All implants became
      integrated and have been supporting a fixed dental bridge for over 3 years with
      no dramatic dimensional changes of the graft. CONCLUSIONS: This case demonstrates
      that particulated autogenous bone and platelet gel may be used for reconstruction
      of the anterior maxilla. Autogenous growth factors in the gel possibly
      contributed to the positive outcome. Controlled clinical studies are needed to
      evaluate the effect of using platelet-rich plasma.

PMID- 12516649
TI  - Imaging technique selection for the preoperative planning of oral implants: a
      review of the literature.
AB  - BACKGROUND: As the use of oral implants for the treatment of partially as well as
      fully edentulous patients has increased the past two decades, more specialized
      radiographic techniques have become available for the preoperative planning of
      oral implant placement. PURPOSE: The goal of this article was to enable
      clinicians to select the appropriate imaging techniques when planning for oral
      implants. MATERIALS AND METHODS: This artide reviews the available literature
      about various imaging techniques and their indication for the preoperative
      planning of oral implants. The advantages and drawbacks of each technique are
      described. A dosimetric overview is given relative to different radiologic
      techniques used in various clinical situations. RESULTS: For preoperative
      planning of implant placement, advantages and drawbacks of the available imaging
      techniques have been considered, which allows guidelines for image technique
      selection to be formulated based on the clinical situation provided, considering
      the diagnostic yield of each technique and the radiation doses involved.
      CONCLUSIONS: From the available literature, it can be stated that many clinical
      situations demand the use of cross-sectional imaging techniques for optimal
      preoperative planning of implant placement. Nevertheless, such techniques are not
      required in cases in which the clinical examination reveals sufficient bone width
      and where standard radiographic examinations, such as intraoral and panoramic
      radiography, reveal adequate bone height and space for implant placement.

PMID- 12516650
TI  - Fetal survival in the rat as affected by intrauterine injection of serum
      containing antiphospholipid antibodies.
AB  - PROBLEM: We wanted to study and examine whether the detrimental effect of
      antiphospholipid antibodies on gestation is locally derived. Therefore, we
      established an experimental rat model, enabling to study the intrauterine effect
      of serum, containing antiphospholipid antibodies, in vivo. METHODS: Sera were
      obtained from five women, having anticardiolipin antibody and lupus
      anticoagulant, and presenting with antiphospholipid antibody syndrome. Pooled
      serum of 150 microL was injected into unilateral uterine horn of each rat on days
      L2-L7 of rat pregnancy. The contralateral uterine horn was used for injection of
      150 microL normal serum or physiologic saline as a control. The rats were
      sacrificed on day L14, and the uterus of each rat was inspected for the presence
      of live and resorbed fetuses. RESULTS: A significant effect on fetal resorption
      and viability was observed following the intrauterine injection of
      antiphospholipid positive serum (APL positive serum), as compared with the
      intrauterine injection of normal serum or saline. A significant increase in fetal
      resorption rate and decrease in fetal viability was noted following the injection
      of APL positive serum on day L6 (P = 0.005 and 0.004, respectively) and day L7 (P
      = 0.003 and 0.003, respectively) as compared with normal serum. A comparison with
      the contralateral injection of saline demonstrated a significant effect of the
      APL positive serum also following the intrauterine injection on days L3 and L5.
      CONCLUSIONS: The current study provides an experimental rat model, which can be
      employed to study the local intrauterine effect of APL positive serum on
      pregnancy outcome and to further assess the efficacy of various treatment
      modalities.

PMID- 12516651
TI  - The effects of IgG purified from women with SLE and associated pregnancy loss on
      rat embryos in culture.
AB  - PROBLEM: Recurrent fetal loss occurs in approximately 1% of women. Autoimmune
      causes have been suggested as a factor in some of these cases. High rates of
      intrauterine fetal growth retardation and increased incidence of prematurity is
      associated with systemic lupus erythematosus (SLE) and the anti-phospholipid
      syndrome (APS). Autoantibodies from sera of SLE/APS patients affect reproductive
      outcome in pregnant mice, as was studied in vivo, where injection of
      immunoglobulin (Ig)G purified from patients with APS to mice caused fetal
      resorptions and growth retardation. METHODS: In order to investigate the direct
      effect of IgG purified from women with SLE or APS on the growth and viability of
      embryos, we cultured 11.5-day old-rat embryos in their yolk sacs in the presence
      of IgG purified from SLE and APS patients. RESULTS: IgG purified from SLE and
      recurrent pregnancy loss (RPL) patients affected directly the embryo and yolk sac
      reducing their growth. The purified IgG positive for anti-cardiolipin/anti-DNA
      antibodies reduced yolk sac and embryonic growth more than sera negative for
      these antibodies. CONCLUSION: Various antiphospholipid antibodies affect
      differently the growth and development of the embryo and the placenta.

PMID- 12516652
TI  - Nasal immunization with diphtheria toxoid conjugated-CD52 core peptide induced
      specific antibody production in genital tract of female mice.
AB  - PROBLEM: The common mucosal immune system (CMIS) has developed as a barrier for
      the numerous encounters between the host and various pathogens. It is possible to
      exploit this system to induce secretion of IgA antibody which inhibits sperm
      penetration in the female genital tract. In this study, the immunogenicity of a
      human sperm surface antigen (CD52) introduced by intranasal immunization was
      investigated with a view to developing a contraceptive vaccine. METHOD OF STUDY:
      A synthetic peptide corresponding to CD52 core peptide (GQNDTSQTSSPS) was
      prepared and conjugated with diphtheria toxoid (DT) as a carrier protein. The
      immunogen was given to mice with DOTAP:cholesterol liposome adjuvant
      intranasally, followed by determination of Ig and IgA class antibody levels in
      the sera and vaginal washes. RESULTS: The CD52 core peptide elicited IgA class as
      well as Ig antibodies both in the sera and vaginal secretions after intranasal
      immunization. An additional nasal inoculation after decrease of the antibody
      titer raised the antibody level to its highest level during the experiment.
      CONCLUSIONS: These results indicate that the CMIS could induce Ig and IgA class
      antibodies reactive to CD52 core peptide in the female genital tract. Intranasal
      immunization of a sperm-specific antigen would be a promising regimen for a safe
      and easy contraceptive vaccine.

PMID- 12516653
TI  - T and B lymphocyte subsets in patients with unexplained recurrent spontaneous
      abortion: IVIG versus placebo treatment.
AB  - PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent
      spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with
      intravenous immunoglobulin (IVIG). METHOD OF STUDY: Forty-one women with a
      history of unexplained RSA were examined during first trimester of pregnancy
      before IVIG or placebo treatment and after pregnancy. The results were compared
      with five healthy, non-pregnant women and five women in the first trimester of
      normal pregnancy. Circulating lymphocyte subsets with focus on T-cell
      subpopulations were determined by flow cytometry. RESULTS: The proportions of
      human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T
      killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas
      the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during
      first trimester pregnancy of RSA women compared with pregnant normal controls. T
      and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG
      or placebo group. CONCLUSIONS: In RSA patients, the immune system seems to be
      activated in contrast to the suppression noted in normal pregnancy.

PMID- 12516654
TI  - High serum interleukin-8 levels in afro-caribbean women with pre-eclampsia.
      Relations with tumor necrosis factor-alpha, duffy negative phenotype and von
      Willebrand factor.
AB  - PROBLEM: Pre-eclampsia is characterized by neutrophil activation. Interleukin-8
      (IL-8) is a strong neutrophil chemo-attractant and activator. METHOD OF STUDY: We
      measured serum IL-8 in 13 pre-eclamptic Afro-Caribbean women and 13 gestational
      age-, race- and parity-matched normotensive and non-proteinuric controls. We also
      determined serum tumor necrosis factor-alpha (TNF-alpha), the phenotypes of the
      IL-8 binding Duffy blood group antigen receptor and the von Willebrand factor
      (vWF) plasma levels. RESULTS: Serum IL-8, TNF-alpha, Duffy negative phenotype
      frequency and plasma vWF were higher in pre-eclamptic women compared with
      controls. IL-8 correlated positively with both TNF-alpha and vWF in the entire
      study group. CONCLUSIONS: Higher IL-8 levels in pre-eclampsia may result from
      increased production (secondary to increased TNF-alpha levels) and/or reduced
      clearance (related to a high frequency of Duffy negative phenotype).

PMID- 12516655
TI  - Chemical pregnancies: immunologic and ultrasonographic studies.
AB  - PROBLEM: Implantation of the embryo determines successful from unsuccessful
      cycles after in vitro fertilization (IVF) and embryo transfer (ET). The purpose
      of this study was to compare immunologic risk factors among women experiencing
      implanation failure characterized by a negative pregnancy test after IVF/ET and
      those experiencing chemical pregnancies. In addition ultrasonographic measurement
      of gestational sac size from 24 to 35 days from last menstrual period (LMP) were
      compared between chemical pregnancies and other pregnancy outcomes. METHODS OF
      STUDY: Blood samples from 122 women experiencing IVF implantation failure with a
      negative pregnancy test after ET and 20 women with chemical pregnancies were
      evaluated for the presence of antiphospholipid antibodies (APA), antinuclear
      antibodies (ANA), circulating embryotoxins (ETA) and elevated levels of natural
      killer (NK) cells. Gestational sac size measured from 24 to 35 days form LMP were
      compared according to pregnancy outcome: term birth (n = 46), ectopic pregnancy
      (n = 49), spontaneous abortion (n = 56) and chemical pregnancy (n = 20). RESULTS:
      Women experiencing chemical pregnancies had a higher frequency of APA than women
      with implantation failure associated with a negative pregnancy test (80% versus
      28%, P < 0.0001). The prevalence of ANA, elevated NK cells and ETA was not
      different between the two groups. The mean gestational sac size from 24 to 35
      days from LMP did not differ when chemical pregnancies were compared with
      pregnancies progressing longer than 35 days. The maximal gestational sac diameter
      among chemical pregnancies was 3.8 mm. CONCLUSION: Mechanisms involved in
      implantation failure associated with a negative pregnancy test may be different
      from those involved in chemical pregnancies. Chemical pregnancies may be the
      result of defective angiogenesis.

PMID- 12516656
TI  - Immunosuppressive properties of follicular fluid and media conditioned by zygotes
      correlate with subsequent conception in in vitro fertilization.
AB  - PROBLEM: Our objective in this study was to correlate immunosuppressive
      properties of follicular fluid (FF) and media conditioned by zygotes and early
      embryos with the occurrence of conception in an in vitro fertilization (IVF)
      program. METHOD OF STUDY: Fifty-seven IVF patients were studied. Donor
      lymphocytes were incubated with mitogens and FF from mature oocytes or
      conditioned media from zygotes and early embryos. Proliferation was assessed by
      radioactive thymidine incorporation. Proliferation Index (PI) was the ratio
      between radioactive labeling of lymphocytes incubated in the presence and absence
      of a mitogen. RESULTS: The FFs and media conditioned by zygotes from conception
      cycles had higher immunosuppressive activity than those from non-conception
      cycles. CONCLUSIONS: Immunosuppressive activity present in FF and media
      conditioned by zygotes may be a major determinant of conception in IVF, and may
      serve as a marker for embryo quality.

PMID- 12516657
TI  - In vitro modulation of protective antibody responses by estrogen, progesterone
      and interleukin-6.
AB  - PROBLEM: We have previously demonstrated that the addition of placental
      interleukin-6 (IL-6) to murine hybridomas increased asymmetric antibody
      synthesis. Here we analyze whether progesterone (Pg) and estrogen (E2) affect
      asymmetric antibody synthesis by modulating IL-6 production in hybridoma cells.
      METHOD OF STUDY: Hybridoma 112D5 B cells were cultured with E2, Pg or recombinant
      IL-6. Cell proliferation was assessed by 3H-thymidine incorporation, and
      asymmetric antibodies were measured in culture supernatants by Con A fixation and
      enzyme-linked immunusorbant assay (ELISA). E2 and Pg-receptors (ER and PR) were
      evaluated in whole cell extracts by Western blot. IL-6 was measured in culture
      supernatants by ELISA. RESULTS: 112D5 expressed both PR and ER, which were
      differentially regulated. At 48 hr, Pg and E2 slightly decreased cell
      proliferation whereas IL-6 did not. As well as IL-6, 10(-10) M Pg but not E2
      induced asymmetric antibody production. Interestingly, Pg at 10(-6) M decreased
      asymmetric antibody synthesis by hybridoma cells. Finally, mainly Pg but also E2
      increased IL-6 synthesis, although IL-6 levels did not correlate with asymmetric
      antibodies synthesized in the presence of E2 or Pg. CONCLUSIONS: In cells
      expressing both ER and PR, we could demonstrate that steroids participate in
      humoral immune responses by modulating asymmetric antibody synthesis. IL-6 proved
      to be only partially involved. Other possible mechanisms involved in the effect
      of Pg on blocking antibody responses and their contribution to a successful
      pregnancy are discussed in the paper.

PMID- 12516658
TI  - High altitude residence during pregnancy alters cytokine and catecholamine
      levels.
AB  - This study assessed the impact of high altitude residence during pregnancy on
      parameters of maternal immune and endocrine system function. Urinary
      catecholamines, and serum cytokines, estriol, and cortisol were assessed during
      pregnancy in women living at moderate or high altitude. Women residing at high
      altitude exhibited elevated levels of proinflammatory cytokines only during
      pregnancy, and tended to have higher levels of catecholamines during pregnancy
      than women living at lower altitude. These data suggest that the combination of
      high altitude and pregnancy alters the maternal neural-immune axis in a manner
      that may predispose women to suboptimal birth outcomes.

PMID- 12516659
TI  - Neuromelanin in the human brain: a review and atlas of pigmented cells in the
      substantia nigra.

PMID- 12516660
TI  - Focussing on excellence.

PMID- 12516661
TI  - GDC annual retention fee--a legal point of view.

PMID- 12516662
TI  - Dentistry in the military.

PMID- 12516663
TI  - Longevity of restorations.

PMID- 12516664
TI  - What is a dental emergency?

PMID- 12516665
TI  - Problems in dentistry.

PMID- 12516666
TI  - Preparing veneer crowns.

PMID- 12516667
TI  - Surgical emphysema following routine preparation.

PMID- 12516668
TI  - Further statistics in dentistry. Part 2: Research designs 2.
AB  - To facilitate statistical discussion, it is essential to have an understanding of
      factors, effects, interactions, confounding, bias, estimation and hypothesis
      testing, to name but a few terms commonly used in statistical investigations in
      dentistry. These terms were explained in the previous paper in this series. This
      second paper is concerned with describing and differentiating between the various
      research designs that may be adopted.

PMID- 12516669
TI  - Periapical ameloblastoma--a case report.
AB  - Ameloblastomas, although often benign, are locally aggressive odontogenic
      lesions. Presentation of this lesion as a pericoronal radiolucency associated
      with an impacted tooth is well documented. Presentation of this lesion as a
      solitary periapical radiolucency associated with a non-impacted tooth however, is
      rare. Periapical presentation of this lesion may confuse practitioners.

PMID- 12516670
TI  - Visual/verbal analogue scales: examples of brief assessment methods to aid
      management of child and adult patients in clinical practice.
AB  - The flexible use of a visual/verbal analogue scale--the thermometer--is described
      as a means of monitoring patients' levels of cognitive fear, trust, pain and self
      esteem during treatment visits. Variations for use with very young children and
      those with physical and learning disabilities are also described.

PMID- 12516671
TI  - Optical power outputs, spectra and dental composite depths of cure, obtained with
      blue light emitting diode (LED) and halogen light curing units (LCUs).
AB  - OBJECTIVE: To test the hypothesis that a prototype LED light curing unit, (LCU),
      a commercial LED LCU and a halogen LCU achieve similar cure depths, using two
      shades of a camphorquinone photoinitiated dental composite. To measure the LCUs'
      outputs and the frequency of the LED LCU's pulsed light, using a blue LED array
      as a photodetector. DESIGN: Cure depth and light output characterisation to
      compare the LCUs. SETTING: An in vitro laboratory study conducted in the UK.
      MATERIALS AND METHODS: The LCUs cured A2 and A4 composite shades. A penetrometer
      measured the depth of cure. Analysis was by one-way ANOVA, two-way univariate
      ANOVA and Fisher's LSD test with a 95% confidence interval. A power meter and
      spectrograph characterised the LCUs' emissions. A blue LED array measured the
      pulsed light frequency from an LED LCU. RESULTS: Statistically significant
      different LCU irradiances (119 mW/cm2 to 851 mW/cm2) and cure depths (3.90 mm SD
      +/- 0.08 to 6.68 mm SD +/- 0.07) were achieved. Composite shade affected cure
      depth. A blue LED array detected pulsed light at 12 Hz from the commercial LED
      LCU. CONCLUSIONS: The prototype LED LCU achieved a greater or equal depth of cure
      when compared with the commercial LCUs. LEDs may have a potential in dentistry
      for light detection as well as emission.

PMID- 12516672
TI  - Attitudes and trends of primary care dentists to continuing professional
      development: a report from the Scottish dental practitioners survey 2000.
AB  - OBJECTIVES: To describe the current and intended continuing professional
      development activity of dentists in general and community practice. DESIGN: A
      cross-sectional survey by postal questionnaire. METHODS: A semi-structured
      questionnaire was sent to all general practice and community dentists identified
      from the dental practices division as being in practice in Scotland. The issues
      addressed included personal demographics, current working patterns and job
      satisfaction, training and professional development and finally career and
      working intentions. RESULTS: Of the 1,917 questionnaires sent to general dental
      practitioners (GDPs), 1,357 were returned useable (70% response rate); 212 of the
      283 questionnaires to community dental practitioners (CDPs) were returned giving
      a 75% response rate. Of the responders, 89% of GDPs (1,188) and 95% of CDPs (178)
      reported participating in some form of CPD in the preceding year. One sixth of
      GDPs (211) and one third of CDPs (62) had a further qualification. Short courses
      such as Section 63 were very popular with over 90% of GDPs, but more than half
      the respondents did not think that further qualifications would enhance their
      career prospects. The most commonly identified barriers to further qualifications
      were heavy clinical commitments (78%), with 73% citing the substantial cost with
      no additional benefit. Over a third of GDPs under the age of 30 indicated they
      intended to sit a postgraduate qualification, but this fell to 12% for those aged
      over 30. The number of dentists identified on a career break was low (18).
      CONCLUSION: Two years before implementation of the General Dental Council's
      mandatory revalidation scheme, over 90% of Scottish primary care dentists
      reported active participation in continuing professional development. Future
      initiatives must be sufficiently sophisticated to fulfil the educational needs of
      different age groups, and to focus on part-time and career break dentists as well
      as full-time practitioners. It is important to establish career pathways in
      dental primary care. Part-time modular courses such as Masters degrees in primary
      care based dentistry may be one solution. An increased number of part-time posts
      for primary care dentists in secondary dental care may increase the skill base
      and also increase service provision in secondary care establishments. These
      pathways should create an opportunity to adequately reward those who continue to
      develop the knowledge and skills necessary for a technically demanding healthcare
      profession.

PMID- 12516674
TI  - Designing the next generation of a sonic toothbrush.
AB  - With the goal of aiding consumers' ability to achieve better oral health, oral
      hygiene products continue to evolve. Powered toothbrushes are an increasing part
      of this oral hygiene effort. This article summarizes the clinical and sensory
      testing associated with the Sonicare Elite, a new generation of sonic toothbrush.
      Important aspects of brush design such as bristle motion, head and neck shape,
      bristle configuration and trim, ergonomic design, and user interface are
      discussed. Further, the article discusses the mix of objective clinical and
      laboratory tests and subjective sensory and consumer tests that are utilized to
      ensure the product design meets the consumer's desire to achieve better oral
      health in a manner that is both pleasing and effective.

PMID- 12516673
TI  - A comparative investigation of dental and medical student's motivation towards
      career choice.
AB  - OBJECTIVE: A number of recent studies have investigated the motivations
      underlying the career choice of dental and medical students, suggesting that they
      may be very different. However, as yet, no studies have been conducted which
      provide a direct comparison of dental and medical students studying in the same
      place. Accordingly, the aim of this investigation was to conduct a survey which
      directly compared the motivation of a selection of dental and medical students at
      Manchester University. STUDY DESIGN: A questionnaire was developed for this study
      on the basis of previous surveys investigating the motivations of dental and
      medical students towards career choice. Six dimensions were covered in the
      questionnaire including: status and security; the nature of the occupation;
      career opportunities; patient care and working with people; use of personal
      skills; and interest in science. In addition, students were asked about the role
      of work experience in either dentistry or medicine. The questionnaire was
      distributed to 80 medical students and 80 dental students chosen from a random
      selection of lecture slots. RESULTS: The results were analysed using the Mann
      Whitney U test. Statistically significant differences were revealed in all six
      areas of career choice motivation. For instance, dental students were
      significantly more likely to be motivated by factors relating to status and
      security and the nature of their occupation (eg regular working hours, self
      employment and independence). By contrast, medical students were significantly
      more likely to be motivated by factors relating to career opportunities, patient
      care and working with people, use of personal skills, and interest in science.
      Work experience was a strong motivating factor in the case of both dental and
      medical students (though especially for dental students). CONCLUSIONS: In
      comparison with dental students, medical students manifested a more professional
      attitude in which altruism and intellectual challenge constituted central
      motivating factors. By contrast, dental students demonstrated more of a
      commitment to personal and financial gain. The paper queries how useful such
      attitudes are to a re-oriented dental profession whose aspiration is to provide
      more accountable and community oriented services.

PMID- 12516675
TI  - Comparison of the interproximal plaque removal efficacy of two powered
      toothbrushes using in vitro oral biofilms.
AB  - PURPOSE: To compare the efficacy of interproximal plaque removal beyond the
      bristles by two electric toothbrushes, the new Sonicare Elite and Braun Oral-B
      3D, in an in vitro model replicating the brushing of interproximal plaque as
      would occur in vivo. MATERIALS AND METHODS: Oral biofilms were grown, in vitro,
      in a constant-depth film fermenter on a hydroxyapatite (HA) disc substratum.
      Brushing experiments were conducted in a brushing machine representing the
      brushing of interproximal plaque between mandibular molars. The HA discs with
      oral biofilms were located a minimum of 1.6 mm away from the bristles. The
      efficacy of plaque removal was assessed by enumeration of the percentage of
      viable bacteria removed from the biofilms by 5 seconds of brushing with the brush
      motors either activated or inactivated. RESULTS: In the activated state, both
      brushes removed a significantly higher percentage of plaque bacteria compared to
      the inactive brushes (Braun, P = 0.002; Sonicare, P = 0.005). The percentage of
      plaque bacteria removed by the Sonicare Elite (32.23%) beyond the bristles was
      significantly greater (P = 0.012) than that removed by the Braun Oral-B 3D
      (9.48%) in this model system.

PMID- 12516676
TI  - Development of a laboratory model to assess the removal of biofilm from
      interproximal spaces by powered tooth brushing.
AB  - PURPOSE: To develop an interproximal laboratory model to compare the potential
      effectiveness of powered brushing to remove biofilm plaque from interproximal
      spaces beyond the reach of bristles. MATERIALS AND METHODS: Streptococcus mutans
      biofilms were first grown on glass microscope slides in a drip-flow reactor. The
      slides were removed and positioned in the interproximal model. Each slide was
      exposed to 15 seconds powered brushing with either the Sonicare Elite or the
      Braun Oral-B 3D Excel. The thickness of the biofilm was measured with confocal
      microscopy at various distances from the bristle tips. RESULTS: The Sonicare
      Elite reduced the thickness of biofilm by 57% at a distance of 0-5 mm from the
      bristle tips, 53% at 5-10 mm and 43% at 10-15 mm, relative to biofilm in areas
      unexposed to brushing. All reductions in thickness were statistically significant
      (P < 0.01). The Braun Oral-B 3D Excel reduced the biofilm thickness by 16%, 13%,
      and 19% at the same distances respectively, but the thickness reductions were not
      statistically significant from those in the unexposed areas (P > 0.1).

PMID- 12516677
TI  - Clinical evaluation of the plaque removal efficacy and safety of the Sonicare
      Elite toothbrush.
AB  - PURPOSE: To compare the clinical efficacy and safety of a new oral hygiene
      device, the Sonicare Elite toothbrush, with the established efficacy and safety
      of the original Sonicare toothbrush (Sonicare Advance). MATERIALS AND METHODS:
      These two products were evaluated in a 2-week, crossover, single blind clinical
      trial with 45 subjects. At the baseline visit, a soft-tissue intraoral exam was
      performed and subjects were randomly assigned to the first treatment. Subjects
      were given each product for a period of 7 days to become familiar with its use.
      After the familiarization period, subjects reported for two clinical evaluations.
      Both plaque removal efficacy and safety were recorded at each evaluation. Plaque
      was scored using the Turesky Modification of the Quigley-Hein plaque index and
      safety recorded by an intraoral examination of the soft tissue. After the first
      treatment arm, subjects crossed over to the other treatment arm and repeated the
      product use and evaluation sequence. Paired analysis (two-way analysis of
      variance) was used to detect differences between the two groups. RESULTS: The
      results indicated that both devices were effective in removing supragingival
      plaque. The Sonicare Elite was statistically superior, on a percentage reduction
      basis, in removing supragingival plaque from the dentition taken as a whole
      (ANOVA; P < 0.05) and was particularly better in hard-to-reach areas such as
      posterior teeth and interproximal sites (ANOVA; P < 0.05). Neither treatment
      group exhibited soft tissue concerns, confirming the safety of both these oral
      hygiene products.

PMID- 12516678
TI  - Comparison of the Sonicare Elite and a manual toothbrush in the evaluation of
      plaque reduction.
AB  - PURPOSE: To compare the clinical efficacy and safety of a new oral hygiene
      device, the Sonicare Elite toothbrush, with a soft-bristled manual toothbrush
      (Oral-B 35). MATERIALS AND METHODS: This study was designed as a single-blind
      crossover with two arms. A sample of 25 subjects who met the entrance criteria
      was divided into two sequences at random: manual-Sonicare Elite, or Sonicare
      Elite-manual. Within each treatment arm, subjects were given a dental cleaning
      and polish, and written brushing instructions, and were allowed to use the
      assigned brush for at least 10 days at home before reporting for two plaque
      reduction evaluations. Upon completion of the first treatment arm, subjects were
      assigned the remaining brush and repeated the same protocol as before. Pre- and
      post-brushing scores were recorded at all visits after 12-18 hours of overnight
      plaque accumulation and were used to calculate a plaque reduction score at each
      evaluation. The scores were then averaged over the repeated visits with the same
      brush and the averages from the two brushes were paired within subjects. ANOVA
      was performed to determine if a difference existed between the two groups in
      terms of overall plaque reduction. RESULTS: The Sonicare Elite achieved a
      significantly greater reduction in plaque than the manual toothbrush (36.0%
      compared to 25.7%; P < 0.05). No adverse events related to either brush were
      reported during the study.

PMID- 12516679
TI  - Evaluation of toothbrush-induced dentin substrate wear using an in vitro ridged
      configuration model.
AB  - PURPOSE: To measure the dentin substrate wear associated with toothbrush use
      utilizing an in vitro specimen modeled to simulate the prominences of teeth and
      thus more closely simulate the clinical situation. MATERIALS AND METHODS: Dentin
      sections were cast within resin to produce a specimen configuration with three
      half-round ridges: a central ridge containing dentin (3 x 10 mm) and two similar
      ridges on each side of the central ridge. The specimens were brushed for the
      equivalent of the amount of time an individual tooth surface would be brushed in
      a 2-year period using a machine that simulated typical movement of a toothbrush
      across the specimen under controlled load and fluid conditions. Brushing was done
      with either a manual toothbrush (MTB), the Braun Oral-B 3D Excel (PTB1) or the
      Sonicare Elite (PTB2) and various loads. Dentin substrate loss was measured by
      profilometry. RESULTS: Using this ridged specimen configuration, the results
      showed that the MTB and PTB1 had the highest amount of dentin substrate wear in
      both average depth and average maximum depth measurements. Increased toothbrush
      force from 90 g to 150 g increased the dentin substrate wear of both PTBs. PTB1
      produced approximately 4-5 times greater average wear than PTB2 (P < 0.05).

PMID- 12516680
TI  - Thrombolytic therapy.
AB  - The therapeutic use of thrombolytic agents is the natural result of the
      increasing understanding of the pathophysiologic mechanisms underlying normal and
      deranged thrombosis and fibrinolysis. Plasminogen activators capable of
      increasing the production of plasmin exhibit considerable efficacy in the
      treatment of a variety of arterial and venous thrombotic disorders. The ideal
      thrombolytic agent has yet to be developed but the desired clinical result of
      rapid opening of the thrombosed vessel without reocclusion, without activation of
      systemic fibrinogenolysis, and without a risk of hemorrhage is well defined.
      Clinical studies clearly demonstrate that the addition of a variety of adjunctive
      agents to the available thrombolytics enhances benefit without inordinate risk.
      The addition of intravascular angioplasty and stenting to thrombolysis increases
      the potential long-term benefit. Newer thrombolytic agents and new protocols for
      the use of existing therapies offer the promise of saving many who would
      otherwise succumb to coronary or cerebral arterial thrombosis or to venous
      thromboembolism.

PMID- 12516681
TI  - Thrombophilic causes of retinal vascular thrombosis: etiology and treatment
      outcomes.

PMID- 12516682
TI  - Effects of a synthetic factor Xa inhibitor (JTV-803) on various laboratory tests.
AB  - Synthetic direct inhibitors of factor Xa are capable of prolonging the global
      anticoagulant assay times in a concentration-dependent fashion. The relative
      degree of thrombin generation inhibition at an equivalent prolongation is not
      similar to the results observed with heparins and oral anticoagulant drugs. In
      addition, the direct factor Xa inhibitors prolong the Russell's viper venom test
      (RWT) and Heptest clotting times. Ecarin clotting time (ECT) and thrombin time
      (TT) remain unaffected. The kinetics of factor Xa inhibition are markedly
      different than those observed with pentasaccharide and heparins. Therefore, the
      methods developed for heparins and pentasaccharides may not be applicable for the
      monitoring of factor Xa inhibitors. To test the feasibility of using the
      prothrombin time (PT), International Normalized Ratio (INR), activated partial
      thromboplastin time (aPTT), Heptest, thrombin time, RVVT, ECT, and a modified
      anti-Xa amidolytic assay, to monitor a synthetic factor Xa inhibitor, normal
      human pool plasma samples were spiked with a synthetic factor Xa inhibitor in the
      concentration range of 0 to 1 microg/mL and 0 to 25 microg/mL. Different
      laboratory tests were performed and INR and other ratios were calculated. The
      anticoagulant effects on whole blood were measured using the activated clotting
      time (ACT). Further studies on the effect of factor Xa inhibitor on platelet
      aggregation; factor II, VII, and X functional levels; and fibrinopeptide A (FPA)
      generation were carried out at equivalent INR levels in comparison to oral
      anticoagulant and antithrombin agents. FPA generation at equivalent anticoagulant
      level in comparison to heparin (twice the baseline) was also carried out. Factor
      Xa inhibitor produced a concentration-dependent prolongation of the ACT. ACT was
      doubled at a concentration of 4 to 5 microg/mL. There was a marked difference in
      the prolongation of the PT by a synthetic factor Xa inhibitor dependent on the
      ISI of the PT reagent used. When the results were calculated to determine INR,
      marked variations were noted between the recombinant thromboplastin and rabbit
      brain thromboplastin. The rabbit brain thromboplastin reagent gave markedly high
      INR values. Similar results were observed when different aPTT reagents were
      studied. In the anti-Xa assay, modification of the incubation time was employed
      to extend the proper sensitivity range. These studies warrant further
      investigation to understand the mechanism of action of factor Xa inhibitors.

PMID- 12516683
TI  - Low-molecular-weight heparin in arterial reconstructive surgery: a double-blind,
      randomized dose-finding trial.
AB  - Periprocedural and postprocedural anticoagulation during arterial reconstructive
      surgery (ARS) with intravenous heparin is standard of care. The general use and
      correct dosage of low-molecular-weight heparin, however, are still under debate.
      A prospective, randomized, double-blind trial was performed with a parallel group
      comparison of four dose regimen of a low-molecular-weight heparin, reviparin
      sodium, in patients undergoing major ARS. Sixty-five patients were randomly
      allocated to receive twice-daily subcutaneous injections of reviparin, 3500
      (group A, n=17), 4200 (group B, n=16), 5950 (group C, n=16), and 7000 (group D,
      n=16) anti-Xa IU per day. Patients were eligible for the trial if they had
      angiographically proven peripheral arterial obstructive disease with a planned
      arterial reconstruction of the infrarenal aorta, iliaca artery, or femoralis
      artery. Fifty-nine patients completed the trial. The goal was to determine the
      optimal dose of the low-molecular-weight heparin to achieve a minimum of early
      vascular events (less than 12%) with a minimum of major bleeding events (less
      than 10%) during a short-term follow-up of up to 8 postoperative days. There was
      no reocclusion in the entire population. Patients randomized into the two lower
      dose groups (A and B), however, experienced a relatively high incidence of
      restenosis, whereas patients enrolled in group D, receiving the highest dose of
      reviparin, experienced an unacceptably high rate of bleeding events (all bleeds,
      43%; major bleeding, 14.3%). Thus, the optimal dose of reviparin sodium to be
      administered in patients undergoing major ARS is half the therapeutic dose: 5950
      to 6300 anti Xa IU (75-85 anti Xa IU/kg body weight per day). Patients included
      in group C had no major bleeding event (95% confidence interval, 0% to 6.6%), a
      significant improvement of the doppler ankle-brachial systolic pressure index
      (difference of 0.46 +/- 0.29, P=.017), and a higher rate of responders with
      regard to the puls status measured at the tibialis posterior arteries (66.7%)
      compared to groups A and B (46.7% and 54.5%, respectively, P=.086). The efficacy
      and safety of this dosage regimen in comparison to standard of care should be
      further substantiated in larger trials.

PMID- 12516684
TI  - Risk factors and long-term follow-up of patients with the immune type of heparin
      induced thrombocytopenia.
AB  - Dispositional risk factors for developing the immune-type of heparin-induced
      thrombocytopenia (HIT) are yet unclear. This article presents a long-term follow
      up of patients with HIT to define possible risk factors that may increase the
      risk of HIT. The clinical course of acute HIT was analyzed retrospectively in 52
      patients with HIT. Thirteen patients died; 8 due to HIT. A follow-up
      investigation was performed in 28 of the remaining 39 patients 29 +/- 12 months
      after the onset of HIT, including genotyping for the factor V G1691A- and the
      prothrombin G20210A-mutation, measurement of antithrombin, protein C, protein S,
      factor VIII, and factor XII activity as well as the concentration of
      antiphospholipid antibodies. The results were compared to an age- and sex-matched
      control group. New thromboembolic events and re-exposure to heparin were also
      documented. No difference between patients and controls was observed concerning
      the factor V Leiden mutation, the prothrombin mutation, factor XII, antithrombin,
      protein S, or protein C deficiency and antiphospholipid antibodies. Increased
      factor VIII activity was found in 16 of 21 HIT patients compared to 4 of 21
      controls (p=0.0005). New thromboembolic events developed in 5 patients within 9
      months after HIT. One patient had been re-exposed to heparin 9 months after acute
      HIT without any complications. Increased factor VIII activity was frequently
      observed in patients in whom HIT developed. Thromboembolic complications within
      the first months after onset of HIT occurred often.

PMID- 12516685
TI  - Endothelial dysfunction associated with chronic intravascular coagulation in
      secondary pulmonary hypertension.
AB  - Altered endothelial anti-thrombotic properties have been observed in primary and
      secondary pulmonary hypertension. In the Eisenmenger syndrome, correlations of
      these abnormalities with the clinical status and occurrence of chronic
      intravascular coagulation (CIC) have not been confirmed. The purpose of this
      study was to investigate whether the occurrence of CIC, as determined by
      circulating levels of D-dimer is associated with changes in endothelial markers
      in Eisenmenger patients; and to identify variables that correlate with the
      severity of clinical presentation. Twenty-one patients were enrolled (ages, 4-52
      years). Plasma levels of D-dimer, tissue plasminogen activator (t-PA),
      thrombomodulin, and von Willebrand factor antigen (vWF:Ag) were measured with
      enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used
      to differentiate patients with stable (group 1, N=12) from those with unstable
      disease (group 2, N=9). Increased t-PA (p<0.0001) and vWF:Ag (p=0.001) and
      decreased thrombomodulin (p<0.0001) were associated with increased D-dimer levels
      (p=0.0201) in patients. Group 2 had a higher prevalence of affected women
      (p=0.0242), lower arterial oxygen saturation, and higher t-PA levels compared
      with group 1 (p<0.0001, discriminant analysis). t-PA and vWF:Ag correlated
      positively in group 2 (r=0.71, p=0.0309), but not in group 1 (r=0.25, p=NS). Two
      patients in group 2 but none in group 1 had episodes of pulmonary arterial
      thrombosis. Endothelial dysfunction is associated with evidence of CIC and
      correlates to some extent with the severity of symptoms in these patients.

PMID- 12516686
TI  - Tissue factor and thrombomodulin in hemodialysis patients: associations with
      endothelial injury, liver disease, and erythropoietin therapy.
AB  - Patients receiving maintenance hemodialysis (HD) present with hemostatic
      abnormalities, which may be aggravated by comorbid conditions, especially liver
      disease. The factors that influence plasma levels of thrombomodulin (TM), an
      initiator of the anticoagulant protein C pathway, and those of tissue factor
      (TF), which triggers the extrinsic coagulation pathway, were assessed. In 63 HD
      patients, TM and TF levels were higher than those in healthy controls. In
      bivariate analysis, TF positively correlated with TM, and both were directly
      associated with the presence of viral hepatitis B or C marker, serum liver
      enzymes, use of erythropoietin therapy, hemoglobin levels, and duration of HD
      therapy, and inversely correlated with body mass index. TF was also positively
      associated with plasma von Willebrand factor (vWF) antigen, and inversely
      associated with activated partial thromboplastin time. In multivariate analysis,
      increased vWF, alanine aminotransferase, and use of erythropoietin independently
      predicted both TF and TM levels. HD patients with vWF and ALT levels lower than
      middle, and not treated with erythropoietin had normal TF but increased TM
      concentrations compared with levels in healthy controls. Increased plasma levels
      of TM and TF in patients on maintenance HD are surrogates of vascular endothelial
      injury. Liver disease and use of erythropoietin treatment are also important
      determinants of these markers, and should be considered in further studies.

PMID- 12516687
TI  - Thrombocytosis and recurrent hepatic outflow obstruction (Budd-Chiari syndrome)
      after successful thrombolysis: case report and literature review.
AB  - Approximately two thirds of cases of hepatic flow obstruction are due to
      myeloproliferative disorders. Restoration of hepatic blood flow is the essential
      goal of treatment. Thrombolytic therapy seems to achieve good results at least in
      selected cases. A 32-year-old woman is presented, with an intermittent increase
      in platelet count (526-725 x 10(9)/L), two previous spontaneous abortions and
      acute symptomatic occlusion of hepatic veins, and in whom a diagnosis of
      essential thrombocythemia was initially carried out in agreement with the
      polycythemia vera study group criteria. She received recombinant tissue
      plasminogen activator followed by heparin with restoration of normal hepatic
      outflow. Asymptomatic re-occlusion of the hepatic veins was observed 1 year
      later, despite adequate continuous warfarin treatment. Angiography showed marked
      narrowing of the intrahepatic cava vein due to extrinsic compression by an
      enlarged liver, not due to a new thrombosis so that no specific intervention
      could be performed. In the presence of a dearly documented hepatic vein
      thrombosis, thrombolytic therapy should be considered. The patient was given low
      molecular-weight heparin with a dramatic reduction in previously elevated
      fibrinogen level and a good control of the hepatic function.

PMID- 12516688
TI  - Simultaneous deep venous thrombosis and acquired factor VIII inhibitor.
AB  - Acquired hemophilia A is a life-threatening immune-mediated hemorrhagic disorder
      that is most often found in individuals older than 50 who present with an
      unexplained activated partial thromboplastin time (aPTT) prolongation and
      clinically significant bleeding. The prolonged aPTT associated with acquired
      hemophilia A reflects factor VIII activity deficiency due to neutralizing or
      clearing autoantibodies. Deep venous thrombosis, in contrast, is a veno-occlusive
      disorder associated with several distinct hypercoagulable states that can result
      in significant morbidity and mortality due to pulmonary embolism, thrombus
      extension, and the post-thrombotic syndrome. A prolonged aPTT in the setting of
      thrombosis may reflect the presence of a lupus anticoagulant. In the absence of
      accurate diagnosis and the immediate institution of specific therapy, both
      disorders can be fatal. Three cases of acquired factor VIII inhibitors that
      included a prolonged aPTT, bleeding, and duplex ultrasound evidence of deep
      venous thrombosis are presented. The diagnostic and therapeutic challenges posed
      by these cases as well as a proposed mechanism by which pathologic thrombosis can
      develop in a patient with a life-threatening bleeding disorder are discussed.

PMID- 12516689
TI  - Effect of clopidogrel on platelet aggregation and plasma concentration of
      fibrinogen in subjects with cerebral or coronary atherosclerotic disease.

PMID- 12516690
TI  - Bronchoalveolar lavage in the diagnosis of pulmonary infections in the
      immunocompromised.

PMID- 12516691
TI  - Utility of bronchoalveolar lavage in the diagnosis of pulmonary infections in
      immunosuppressed patients.
AB  - AIM: To evaluate the utility of bronchoalveolar lavage (BAL) in immunocompromised
      patients. MATERIAL AND METHODS: We studied BAL cytology and microbiological
      culture in 16 kidney transplant recipients (Group A), 14 dialysis patients (Group
      B) and eight HIV positive patients (Group C) suspected of having pulmonary
      infections. A group of 21 individuals without pulmonary diseases were studied as
      controls. RESULTS: A comparison of the cytological profile in controls and study
      groups showed that percentages of lymphocytes and neutrophils were significantly
      increased in all three patient groups as compared to controls, BAL bacterial
      cultures were positive in 4, 3 and 4 cases of Group A, B and C, respectively.
      Direct examination of BAL cytosmears helped in detecting cytomegalovirus
      inclusions, acid fast bacilli and Pneumocystis carinii in 3, 2 and 5 cases of
      Group A, B and C, respectively though microbial cultures were negative. The
      sensitivity of BAL cytology was found to be 76.3%, whereas that of microbial
      culture was only 31.5%. The diagnostic yield of BAL was 68.75%, 71.42% and 100%
      in the Groups A, B and C, respectively, while it was 76% when all three groups
      were considered together. BAL cytology yielded the diagnosis in 47.36% of cases,
      a combination of BAL cytology and culture in 23.68% and culture alone in 5.3% of
      cases. CONCLUSIONS: BAL is useful relatively non-invasive investigative tool in
      the rapid diagnosis of infections in immunocompromised patients. BAL cytology was
      found to be more useful than microbial cultures.

PMID- 12516692
TI  - Evaluation of role of acute intermittent peritoneal dialysis in resistant
      congestive heart failure.
AB  - AIMS AND OBJECTIVES: To evaluate the role of acute intermittent peritoneal
      dialysis (PD) in resistant congestive heart failure (CHF). MATERIAL AND METHODS:
      The study was conducted on 20 adult patients of resistant CHF. These patients
      were subjected to 12 cycles of acute intermittent hypertonic peritoneal dialysis.
      Improvement was monitored by clinical symptomatology, echocardiography,
      measurement of ultrafiltration and quantity of sodium transferred. RESULTS: There
      was improvement in clinical symptomatology. There was significance improvement in
      left ventricular (LV) function as evidenced by improvement in ejection fraction
      from a predialysis value of 43.35 +/- 16.73% to a post dialysis value of 53.55 +/
      14.53%. The ultrafiltration and quantity of sodium transferred was also
      significant. CONCLUSIONS: Acute intermittent hypertonic peritoneal dialysis is an
      effective and safe treatment modality in patients of resistant CEF. The patients
      subsequently respond well to medical therapy.

PMID- 12516693
TI  - Association of microalbuminuria with carotid intima-media thickness and coronary
      artery disease--a cross-sectional study in Western India.
AB  - OBJECTIVE: Microalbuminuria, a slightly elevated albumin excretion in the urine,
      is considered a novel atherosclerotic risk factor, both in diabetics subjects and
      in general population. Carotid intima-media thickness assessed non-invasively by
      a B-mode ultrasound has been recently shown to be an early marker for
      atherosclerosis. This study aims at determining the role of microalbuminuria as
      an atherosclerotic risk factor and its association with coronary artery disease.
      METHODS: We measured the urine microalbumin excretion and carotid intima-media
      thickness (IMT) in 301 subjects, with or without evidence for coronary artery
      disease (CAD). Microalbuminuria was diagnosed if urinary excretion of albumin
      exceeded 20 microgm/ml. RESULTS: Of the 301 subjects (age group--30-80 years)
      recruited for the study, 194 were males, 107 females. One hundred amd eighteen
      subjects had evidence of CAD as diagnosed by documented hospitalization with
      myocardial infarction or acute coronary syndrome, coronary angiography when
      feasible or non-invasive cardiac evaluation. One hundred and sixty three subjects
      had diabetes mellitus. Microalbuminuria was detected in 74 subjects (24.6%).
      Prevalence of subjects with increased IMT was higher among subjects with
      microalbuminuria compared to normoalbuminuria (42% vs 21.4%, p < 0.003).
      Prevalence of CAD was significantly higher among diabetic subjects with
      microalbuminuria compared to those with normoalbuminuria (Diabetic subjects: 58%
      vs 31.9%, p = 0.002, Non-diabetic subjects: 41.7% vs 37.7%, p = 0.718).
      Multivariate logistic regression analysis using carotid intimal medial thickness
      as a dependent variable revealed a statistically significant association with
      microalbuminuria in diabetic subjects (p = 0.027). CONCLUSION: We conclude that
      microalbuminuria shows a strong association with increased carotid intimal medial
      thickening and coronary artery disease in diabetic subjects in this Western
      Indian population.

PMID- 12516694
TI  - Clinical and biochemical profiles of young diabetics in North-Eastern India.
AB  - OBJECTIVE: We compared the clinical and biochemical profiles of young diabetics
      in North Eastern India. METHODS: Seventy diabetics who were detected at less than
      30 years of age were studied. Patients with ketoacidosis or ketonuria on insulin
      withdrawal were grouped as insulin dependent diabetes mellitus (IDDM), patients
      with history of chronic abdominal pain with or without exocrine pancreatic
      dysfunction who either on ultrasonography (USG) or endoscopic retrograde
      cholangiopancreaticoduodenography (ERCP) revealed pancreatic calcification and/or
      ductal dilatation were grouped as fibrocalculous pancreatic diabetes (FCPD),
      those having BMI < 19 kg/m2 with history or stigmata of childhood malnutrition
      and who were ketosis resistant were taken to be protein deficient diabetes
      mellitus (PDDM)/malnutrition modulated diabetes mellitus (MMDM) and those who
      neither had ketonuria nor history of chronic abdominal pain, malabsorption or
      stigmata of malnutrition were grouped as NIDDM of young (NIDDY). RESULTS: Amongst
      the young diabetics studied FCPD constituted 32.9%, IDDM 28.6%, MMDM 21.4% and
      NIDDY 17.11%. USG abnormalities were observed in 21 of the 23 patients of FCPD.
      Seven out of these showed pancreatic head calcification on X-ray while 14 showed
      pancreatic duct dilatation and calcification or calculi on USG. In the two
      remaining patients, ERCP revealed tortuousity of main pancreatic duct and
      calcification which were not detected on USG. Majority of FCPD and MMDM patients
      revealed insulin resistance on insulin tolerance test (ITT). HDL was
      significantly lower in NIDDY, while VLDL and triglycerides were significantly
      higher in FCPD and MMDM as compared to controls. Microvascular complications of
      diabetes were seen in all these groups, with peripheral neuropathy being more
      common in FCPD (43.5%) and background diabetic retinopathy in NIDDY (41%).
      CONCLUSIONS: We conclude that FCPD and MMDM together form majority (54.29%) of
      young diabetics at our center and a sizeable proportion of them may have
      microvascular complications, even at the time of diagnosis.

PMID- 12516695
TI  - Prevalence of non-diabetic renal disease in type 2 diabetic patients in a
      diabetes centre in Southern India.
AB  - OBJECTIVE: The Aim of Study is to determine the prevalence of non-diabetic renal
      disease among South Indian type 2 diabetic subjects based on renal biopsy.
      METHODS: Three thousand five hundred and ninety subjects with complete records
      were included for the study. One hundred and forty subjects who had proteinuria
      but no evidence of retinopathy undertook a 24 hour proteinuric estimation. Of
      these 140 subjects, 28 subjects had proteinuria > 1,000 mg/day and were subjected
      to renal imaging. Seven subjects were excluded due to renal calculi, cysts or
      contracted kidneys. Of the remaining 21 diabetic subjects, one subject was
      excluded as he had a mild diabetic retinopathy on fundus fluorescein angiography.
      Of the 20 subjects included 18 participated in the renal biopsy study (response
      rate--90%). Renal pathology of these subjects were studied. RESULTS: Of the 18
      renal biopsies, two were excluded due to different reasons. Out of 16 patients,
      eight (50%) had pathological changes suggestive of diabetic etiology, five
      (33.3%) had classical membranous nephropathy, one (6.2%) had tubulo-interstitial
      disease and two (12.5%) were categorized as others with minimal changes. The
      subjects with non-diabetic renal disease had significantly higher creatinine
      clearance (p = 0.024), serum cholesterol (p = 0.036), triglyceride levels (p =
      0.045) and LDL cholesterol (p = 0.048) compared to subjects with diabetic
      nephropathy. CONCLUSION: This study suggests that even in subjects clinically
      suspected to have non-diabetic renal disease many may turn out to have diabetic
      nephropathy on renal biopsy.

PMID- 12516696
TI  - Radiofrequency ablation for accessory pathways: success and variants.
AB  - INTRODUCTION: Radiofrequency ablation (RFA) is currently being advocated as the
      first line of therapy for symptomatic and drug refractory arrhythmias mediated by
      accessory pathways (APs). However, a large database on RFA for APs from India is
      still lacking. METHODS: Four hundred thirty-four patients (298 males, (69%)),
      with APs who underwent RF ablation between January, 1998 and May, 2001 were
      included. The success and variants were evaluated retrospectively from the data.
      RESULTS: The mean age was 36 +/- 11 years. There were 314 (73%) patients with WPW
      syndrome while the other 120 (27%) had concealed APs. Documented tachycardia was
      noted in 406 (91%) patients. Forty-six (11%) patients had associated structural
      heart disease (Ebstein's anomaly in 18). The procedure was successful in 414
      (97%) of 425 patients in whom it was attempted. Of those unsuccessful, five had
      epicardial APs, four had multiple APs and two had immediate recurrence of APs.
      RFA was not attempted in nine parahissian pathways. Additional mechanisms were
      seen in 48 (11%) patients with WPW syndrome (14 (4.4%) AV nodal reentrant
      tachycardias, 16 (5%) additional concealed APs and 18 (5.7%) multiple APs).
      Coronary sinus diverticulum were detected in 23 (7.3%) patients, and Mahaim-like
      APs were diagnosed in 24 (6?8%) patients. The procedural and fluoroscopy time was
      96 +/- 41 and 19 +/- 13 minutes, respectively. There were no deaths; three
      patients developed pericardial tamponade, which was promptly treated by
      pericardiocentesis. CONCLUSION: Radiofrequency ablation is a safe and effective
      treatment for AP mediated tachycardia, especially for younger patients and
      children in whom life-long drug therapy may not be best option.

PMID- 12516697
TI  - Iodine content of various salt samples sold in Mangalore--a coastal city with
      endemic goitre.
AB  - OBJECTIVE: Iodine deficiency disorders continue to be high despite ban on sale of
      non-iodised salt. In order to assess the effectiveness of salt iodisation
      programme, a study was undertaken to assess the iodine content of salt samples
      sold in Mangalore. MATERIAL AND METHODS: One hundred salt samples were randomly
      collected from shops in Mangalore and iodine content measured using MBI iodine
      testing kits. RESULTS: Only 39 samples had adequate iodine of 15 ppm or more.
      There was a statistically significant difference in the salt samples with
      adequate content in rural versus urban areas (46.6% and 27.5%, respectively, with
      p < 0.05). Branded samples had significantly higher iodine content than non
      branded salt (p < 0.05). Salt sold at Rs.2/- per kg had significantly lower
      iodine content than the salt sold at Rs.3-4/- per kg (p < 0.01). CONCLUSION: Salt
      iodisation programme is poorly implemented in Mangalore probably due to improper
      iodisation, inadequate storage, hot and humid weather conditions and lack of
      public awareness. Public education and education of shop owners regarding their
      role in prevention of iodine deficiency disorders may be of value in this
      direction.

PMID- 12516699
TI  - Atrial fibrillation, stroke and anticoagulation.

PMID- 12516698
TI  - Relative bioavailability of two brands of ornidazole in twelve healthy
      volunteers.
AB  - AIM OF THE STUDY: To determine the bioequivalence of two marketed ornidazole
      formulations in healthy volunteers. METHODOLOGY: A single dose relative
      bioavailability of Ornidazole 1.5 g (3 x 500 mg tablets) of test product (Giro,
      Panacea Biotec Ltd.) and that of standard reference (Dazolic, Sun Pharmaceutical
      Industries), was investigated in healthy adult males. A total of 12 subjects wee
      enrolled in the study and investigations consisted of two treatment phases
      separated by a washout period of seven days. Both treatment phases were of 12
      hours durations each. Blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6,
      8, 10 and 12 hours post-administration of assigned drug product. Appropriate
      fasting restrictions were employed during both the treatment phases. Drug assay
      was done using HPTLC method. The statistical significance of difference in
      pharmacokinetic parameters between preparations was tested using ANOVA. RESULTS:
      The mean peak plasma concentration (Cmax) of 32.67 +/- 4.45 microg/ml was
      achieved at 1.54 +/- 0.81 hours following administration of test product as
      against mean Cmax of 31.55 +/- 5.04 microg/ml at 1.79 +/- 0.89 hours for
      reference standard. The area under time concentration curve (AUC(0-12)) hours was
      261.67 +/- 77 microg/ml hours with reference standard and 265.41 +/- 30.82
      microg/ml hours for test product. CONCLUSION: There was no statistically
      significant difference between the two formulations and the two products

PMID- 12516700
TI  - Medical philately (medical personalities on stamps).

PMID- 12516701
TI  - Pictorial CME. Emphysematous pyelonephritis.

PMID- 12516702
TI  - Antiretroviral therapy: are we aware of adverse effects?
AB  - HIV/AIDS has become a chronic disease thanks to the availability of
      antiretroviral drugs. Many of these antiretroviral drugs are available in India.
      Many more will soon become available. The cost of these drugs is being reduced
      gradually and their use is increasing. However, there are both short term and
      long term side effects. This review focuses on the common potential toxicities of
      antiretroviral drugs and their management. The potential toxicities include
      gastrointestinal effects, hepatitis, hypersensitivity reactions, cytochrome P450
      interactions, mitochondrial toxicity and lipodystrophy syndrome as well as more
      drug-specific adverse effects.

PMID- 12516703
TI  - Unexpected presentations--four cases of lead poisoning.
AB  - OBJECTIVE: To describe the clinical presentation and response to treatment of
      four patients who presented with abdominal pain and were diagnosed to have lead
      poisoning. METHODS: After ruling out the more obvious causes of abdominal pain by
      barium studies, gastrointestinal endoscopies, and biochemical studies, blood lead
      levels were estimated by atomic absorption spectrophotometry. The patients were
      treated with oral d-penicillamine. RESULTS: The four patients had blood lead
      levels from 79 microg/dL to 365 microg/dL. All four of them showed marked
      improvement in their clinical condition and lowering of blood lead levels on
      follow up. CONCLUSIONS: Clinicians need to develop a high index of suspicion of
      lead poisoning as a possible cause of unexplained abdominal pain or altered
      sensorium, especially against a background of environmental lead contamination in
      India.

PMID- 12516704
TI  - Diabetes insipidus in a patient with diabetes mellitus.
AB  - The association of Diabetes Mellitus (DM) and Diabetes Insipidus (DI) without any
      congenital defects is very rare and we report here a case of type 2 diabetes
      mellitus (NIDDM) whose blood sugar was controlled by insulin, developing central
      diabetes insipidus 2 years later, which could be successively controlled by
      synthetic vasopressin.

PMID- 12516705
TI  - Treatment of massive haemoptysis with aminocaproic acid.

PMID- 12516706
TI  - Disseminated cysticercosis.

PMID- 12516707
TI  - Extracranial head and neck circulation aneurysms in a case of polyarteritis
      nodosa.
AB  - Polyarteritis nodosa (PAN) is a rare systemic necrotising medium vessel
      vasculitis. The hallmark of this condition is aneurysms which are seen in
      visceral arteries. Aneurysms of extracranial neck and head vessels are rare. We
      describe a case of PAN who had such aneurysms together with characteristic
      aneurysms in the mesenteric circulation.

PMID- 12516708
TI  - Hodgkin's disease and scleroderma.
AB  - We report here the uncommon association between scleroderma and Hodgkin's disease
      in a 42 years male.

PMID- 12516709
TI  - Bronchial stenosis after blunt chest trauma.
AB  - A young boy who sustained blunt chest trauma 24 months back, presented with
      repeated chest infections. His chest skiagram revealed right hemithorax opaque
      and CT scan of thorax showed collapse of right lung. Fiberoptic bronchoscopy
      helped to diagnose the post-traumatic stenosis of right main bronchus. Laser
      resection was utilized to restore the patency.

PMID- 12516710
TI  - Phototoxic reaction due to clarithromycin.
AB  - An unusual case of phototoxic reaction caused by clarithromycin is being
      presented here as it is not reported in medical literature.

PMID- 12516711
TI  - Tubercular mediastinal lymphadenopathy presenting as superior vena cava syndrome.

PMID- 12516712
TI  - Cerebrotendinous xanthomatosis.

PMID- 12516713
TI  - Acute encephalitis without rash in Warangal, Andhra Pradesh and Vadodara, Gujarat
      associated with measles virus.

PMID- 12516714
TI  - Post-transfusion purpura.

PMID- 12516715
TI  - Gelatinous transformation of marrow: an incidental finding in pancytopenia.

PMID- 12516716
TI  - Radical cure of vivax malaria: five or 14 days?

PMID- 12516717
TI  - MALT lymphoma of thyroid.

PMID- 12516718
TI  - Indian guidelines for the management of rheumatoid arthritis.

PMID- 12516719
TI  - Age-related changes in the human optic nerve.
AB  - BACKGROUND: Recent morphologic research has demonstrated the presence of nerve
      fibres of different diameters in the human optic nerve. The purpose of this study
      was to investigate age-related changes in fibres of the human optic nerve.
      METHODS: We studied the left optic nerve of 50 male cadaveric donors, 16 aged 18
      to 22 years (mean 20 [standard deviation 1.2] years) and 34 aged 68 to 76 years
      (mean 72 [standard deviation 1.6] years). The samples were carefully harvested
      during autopsy from the intracranial portion of the optic nerve. Each nerve was
      cut into four 4-mm segments. After morphologic, histochemical and
      immunohistochemical staining, the optic nerve fibres were counted and measured.
      Each segment was evaluated under light microscopy for microanatomic details,
      glial cells and glial fibrillary acidic protein (GFAP) staining. The protein
      content was determined under biochemical analysis. We performed morphometric
      analysis by examining the optic nerve images quantitatively. RESULTS: Compared
      with the younger group, in the older group there was an increase in mean diameter
      of the optic nerve (p < 0.001), due to an increase in the optic nerve:meningeal
      membrane ratio. There was also an increase in mean optic nerve area (p < 0.001)
      and in mean number of astrocytes and the related GFAP-immunoreactive area (p <
      0.001). The mean number of nerve fibres of large diameter (greater than 4 pm) was
      decreased (p < 0.001). There was no difference in mean protein content of the
      fibres between the two groups. INTERPRETATION: The human optic nerve is sensitive
      to the aging process and may be considered as a model for studies on neuronal
      aging.

PMID- 12516720
TI  - Do we heed the endophthalmitis vitrectomy study in Canada?
AB  - BACKGROUND: The Endophthalmitis Vitrectomy Study (EVS) was a multicentre
      randomized clinical trial designed to guide the management of postoperative
      bacterial endophthalmitis. There is speculation that many physicians do not
      follow its recommendations, despite its intent. We surveyed Canadian
      vitreoretinal surgeons to determine whether surgeons are adopting the EVS
      recommendations in their management of bacterial endophthalmitis after cataract
      surgery. METHODS: A survey was sent to 98 vitreoretinal surgeons across Canada
      who manage postoperative endophthalmitis following cataract surgery. The survey
      explored the management of patients presenting with a hypopyon or suspected
      endophthalmitis, or both, early (up to 2 weeks) after cataract surgery. For
      purposes of comparison with the EVS, the questions were divided into presenting
      visual acuity categories. RESULTS: Of the 98 surgeons 30 (30.6%) responded to the
      survey. The preferred treatment for patients presenting with no light perception
      visual acuity was pars plana vitrectomy (23 respondents [76.7%]); 7 respondents
      (23.3%) preferred vitreous tap/biopsy. All but one of the respondents stated that
      they prefer pars plana vitrectomy for patients presenting with light perception
      vision; the remaining physician preferred either pars plana vitrectomy or
      vitreous tap/biopsy. For patients with hand motions visual acuity, 17 respondents
      (56.7%) would perform pars plana vitrectomy, 11 (36.7%) would perform vitreous
      tap/biopsy, and 2 (6.7%) would perform either procedure. Most of the respondents
      (20 [66.7%]) would perform vitreous tap/biopsy for patients with visual acuity of
      counting fingers, whereas 9 (30.0%) would perform pars plana vitrectomy, and 1
      (3.3%) would perform either procedure. All the respondents indicated that they
      would use intraocular antibiotic therapy for initial treatment, 29 (96.7%) would
      use topical antibiotic therapy, 17 (56.7%) would inject antibiotics
      subconjunctivally, and 1 (3.3%) would use intravenous antibiotic therapy.
      Fourteen respondents (46.7%) would use intraocular steroid therapy.
      INTERPRETATION: Most of the Canadian vitreoretinal surgeons who responded to this
      survey do not follow the recommendations of the EVS.

PMID- 12516721
TI  - Longitudinal analysis of central serous chorioretinopathy and sex.
AB  - BACKGROUND: Stress has been proposed as one of the contributing factors of
      central serous chorioretinopathy (CSC). Because the number of women in the
      workforce has increased dramatically in past decades, their presumed additional
      stress may increase their risk for CSC. We performed a study to determine whether
      the ratio of men to women in whom CSC was diagnosed remained constant between
      1970 and 2000 in our patient population. METHODS: We reviewed the medical records
      of 88 patients (69 males and 19 females) in whom CSC was diagnosed between 1970
      and 2000. Only patients who were noted to have subretinal fluid on stereoscopic
      colour fundus photographs and focal retinal pigment epithelial hyperfluorescence
      on fluorescein angiography were included. Logistic regression analysis was
      performed to determine the probability of a patient's being male over the study
      period. RESULTS: No significant change was found in the proportion of male
      patients in whom CSC was diagnosed over the study period (p = 0.69).
      INTERPRETATION: The ratio of males to females with a diagnosis of CSC did not
      change significantly over 30 years in our study population. If stress is a
      contributing factor of CSC and if women are experiencing increased stress from
      changing societal roles, women may have different adaptations to stress than men,
      or other mechanisms of CSC formation may be present.

PMID- 12516722
TI  - The role of epithelial defects in intralamellar inflammation after laser in situ
      keratomileusis.
AB  - BACKGROUND: A single factor responsible for diffuse lamellar keratitis (DLK)
      after laser in situ keratomileusis (LASIK) has not yet been identified. Various
      theories have been proposed to explain what may trigger this condition. We
      evaluated the role of epithelial defects in interface inflammation and assessed
      the outcome of eyes with DLK with and without epithelial defects. METHODS: We
      reviewed the records of all patients with DLK after LASIK performed at the
      Toronto Gimbel Eye Centre between September 1999 and May 2000. Patients with
      other epithelial problems, such as punctate epithelial erosions, were excluded.
      Patients with an epithelial defect and interface keratitis (group 1) were treated
      with a bandage contact lens and topical steroid therapy; those with interface
      keratitis alone (group 2) were treated with topical steroid therapy. Variables
      examined included the onset and duration of DLK, uncorrected visual acuity, best
      corrected visual acuity, refractive outcome and retreatment rate. RESULTS: A
      total of 1,436 LASIK procedures were performed during the study period. Thirteen
      patients (20 eyes) had DLK after LASIK, in all cases of the sporadic type (i.e.,
      nonepidemic). Of the 20 eyes, 8 had an epithelial disturbance. All the patients
      were followed for at least 3 months. Three eyes (37.5%) in group 1 had
      uncorrected visual acuity before retreatment of less than 20/25, compared with 2
      eyes (16.7%) in group 2. The mean postoperative spherical equivalent was
      significantly higher in group 1 than in group 2 (-0.60 vs. -0.02 dioptres) (p =
      0.01). The retreatment rate was 37.5% (3/8) in group 1 and 16.7% (3/12) in group
      2, a nonsignificant difference. After retreatment the uncorrected visual acuity
      was 20/20 or better in all cases. There were no cases of recurrence of DLK after
      retreatment. INTERPRETATION: Eyes with interface keratitis and an epithelial
      defect have a larger deviation from emmetropia before retreatment than eyes with
      interface keratitis alone. Patients with epithelial defects intraoperatively or
      who are at risk for such defects postoperatively must be monitored carefully, as
      they may be at increased risk for DLK.

PMID- 12516723
TI  - Rhodotorula glutinis endophthalmitis.

PMID- 12516724
TI  - Hypotony after intravenous cidofovir therapy for the treatment of cytomegalovirus
      retinitis.

PMID- 12516725
TI  - Cysticercosis of superior oblique muscle: surgical excision and reconstruction of
      superior oblique tendon.

PMID- 12516726
TI  - Ankle biomechanics.
AB  - The developers of a successful prosthetic implant for ankle replacement must
      consider the biomechanical properties that are unique to this complex joint. The
      prosthesis needs to provide structural support while allowing for motion in the
      sagittal, transverse, and coronal planes. Although the design must conform to and
      function within the soft tissue constraints of the ankle, it is only a component
      of the overall success. Paying attention to leg alignment and meticulous soft
      tissue balancing is essential to a satisfactory outcome.

PMID- 12516727
TI  - Total ankle arthroplasty: a historical perspective.
AB  - The ideal total ankle prosthesis has yet to be determined, but much has been
      learned from early experiences in ankle arthroplasty. Modern implants are
      typically more respectful of anatomic concerns, have found a happy medium of
      constraint, and have found novel approaches to decrease interface stress.
      Biologic fixation has improved on cemented results. Surgical techniques and
      understanding of wound healing and ligamentous deficiency have advanced. Current
      series still have varied results, and longer-term follow-up is needed. Despite
      this, some modern ankle replacements represent significant progress, with
      improved results and survival challenging those of arthrodesis. Further, benefits
      of preserved motion and avoidance of foot arthritis outstrip this traditional
      "gold standard." Today, tempered enthusiasm for the future of total ankle
      arthroplasty is again apparent. A diverse, international effort is underway to
      create a lasting joint implant. Building on the lessons of the past, different
      investigators in different countries, using markedly different prostheses,
      continue to work toward this goal.

PMID- 12516728
TI  - Long-term outcome of ankle arthrodesis.
AB  - The small number of long-term studies performed after successful arthrodesis
      suggests that most patients are satisfied with their outcomes. Some patients,
      however, eventually become limited by pain and degenerative changes elsewhere in
      the foot. Over time, subjacent joint arthritis is highly likely, especially that
      which involves the subtalar and talonavicular joints. (Fig. 1)

PMID- 12516729
TI  - Preoperative considerations in ankle replacement surgery.
AB  - Total ankle arthroplasty continues to evolve as a viable treatment option for end
      stage ankle arthritis. Proper patient selection is a critical aspect of promoting
      a successful result. Acceptable results have been reported in older, low-demand,
      nonobese patients who have osteoarthritis or rheumatoid arthritis. A significant
      percentage of patients with end-stage ankle arthritis, however, are younger
      patients with posttraumatic arthritis. Considerable controversy surrounds the use
      of ankle replacement in younger, more physically active patients and in those
      with significant deformity in the ankle or hindfoot. These patients should be
      approached cautiously because the risks and complications are still significant.
      More studies must be completed and further developments must be made to maximize
      the longevity and functional results of total ankle arthroplasty in future
      designs and applications.

PMID- 12516730
TI  - Ankle replacement: management of associated deformities.
AB  - Ankle arthroplasty is emerging as an alternative to arthrodesis. Restoring and
      maintaining proper bony alignment and muscle balance in the limb is essential if
      there is to be any chance for long-term survival. Deformity can arise above the
      ankle, in the joint itself, or in the foot. Secondary procedures in the foot and
      leg, including osteotomies, fusions and muscle balancing, are performed either
      before or simultaneously with ankle replacement.

PMID- 12516731
TI  - The Agility ankle replacement: the good and the bad.
AB  - The Agility ankle system allows the foot and ankle surgeon the capability of
      addressing most arthritic problems. If care is taken in patient selection,
      physician education, and careful postoperative management a long-term successful
      outcome can usually be achieved. Complications can and do arise, but most can be
      dealt with successfully if recognized early and appropriate steps are taken.

PMID- 12516732
TI  - Experience with the STAR ankle arthroplasty at Wrightington Hospital, UK.
AB  - The STAR prosthesis has been used at Wrightington Hospital since November 1993,
      and from then until June 2002, 280 replacements have been carried out. The
      opinions expressed in this article are based on an ongoing audit of these cases.

PMID- 12516733
TI  - How to avoid specific complications of total ankle replacement.
AB  - The design of the Agility total ankle replacement (DePuy, Warsaw, IN) has
      improved in an effort to address the biomechanic challenges of the ankle joint.
      Certainly further laboratory investigation and clinical trials with ankle
      replacement are needed to improve its position as the major alternative to ankle
      arthrodesis. As the science behind the ankle implants has evolved during the last
      15 years, so has our experience and understanding of some crucial factors
      predisposing to an unsuccessful outcome. Complications such as postoperative
      stiffness, prosthesis subsidence, and residual deformity along with infection and
      wound healing problems jeopardize a successful outcome. Adequate knowledge of
      anatomy and biomechanics, careful preoperative evaluation and planning, and
      strict attention to operative details help minimize the incidence of these
      complications.

PMID- 12516734
TI  - Complications of total ankle replacement.
AB  - Total ankle arthroplasty with second-generation prostheses is gaining popularity.
      Complications do and will occur with this group of replacements, just as they do
      with all other arthroplasties, whether at the knee, hip, elbow, shoulder, or
      wrist. Even if the complications are understood and the preventative measures or
      solutions are well thought out, there is occasionally no clear-cut answer to the
      problem. Although there are many obstacles to a successful outcome, most of the
      complications reported here are preventable with good patient selection and
      technique or at least treatable once they occur.

PMID- 12516735
TI  - The history of the STAR total ankle arthroplasty.
AB  - The STAR ankle replacement prosthesis has almost a 30-year history. The current
      FDA study of the device in the United States is very encouraging. The prosthesis
      does show great promise but needs further study. Further elucidation of the
      postoperative radiographs and the various areas of lucency and their significance
      should be studied. The learning curve for implantation is very steep.

PMID- 12516736
TI  - Clinical experiences with three different designs of ankle prostheses.
AB  - Until 1995, fusion was in our institution the only rational surgical option for a
      severe ankle arthrosis. Consistent reports about good mid- and long-term results
      with ankle replacement allowed us to change our minds. Ankle replacement became
      the gold standard and fusion was then almost totally banished. Because ankle
      arthrosis can be morphologically different from one patient to another, we soon
      believed that one single type of ankle prosthesis would not be the universal
      optimal solution for all patients. We therefore divided the ankle arthrosis into
      three groups. Each group shows the best solution from each of the ankle
      prostheses with which we had gained experience (Agility, STAR, and BP). The
      Agility prosthesis, which was indicated for ankles with extremely damaged
      geometry, did not restore sufficiently the ankle motion. Preoperatively stiff
      ankles remained stiff postoperatively. Additionally, significant residual pain
      was more likely to occur in those patients. These cases did not show significant
      advantages compared with ankle fusion, especially from a functional point of
      view. Fusion for these stiff ankles is therefore today our first treatment of
      choice. In our experience, the malleolar joints do not have to be replaced. Even
      a severe arthrosis at this level does not produce significant pain, provided that
      osteophytes have been removed and joint height has been restored by the implanted
      prosthesis. It is our strong belief that these malleolar joints are also less
      sensitive to pain, similar to the femoropatellar joint. For these reasons, a
      replacement of the malleolar joints and the resurfacing of the talar sides is not
      necessary. Leaving the talar sides untouched requires less bone resection and
      makes the implantation of the talar component easier. Although we obtained good
      results with the STAR prosthesis, we progressively abandoned it because of these
      reasons, and we preferred the BP prosthesis. The BP prosthesis works on the same
      biomechanic principle as the STAR prosthesis. Some features, however, like the
      untouched malleolar joints, the large exposition of the joint, the easier
      adjustments of its position, the possibility of enhancing the press fit, and the
      good short- and midterm results we obtained with it led us to the decision of
      using it as our only design for cases of nice and acceptable arthroses. Even if
      mostly good and excellent results have been achieved with all prostheses
      currently used, some results are still disappointing. Some ankles become stiff
      postoperatively and some remain diffusely painful; the explanations for these
      problems are often difficult to attain. This clearly shows that despite all the
      progress made over the last few years, there is still a lot to be learned about
      ankle arthroplasty.

PMID- 12516737
TI  - Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current
      concepts.
AB  - Multiple, biochemical cascades contribute to the pathogenesis of neonatal hypoxic
      ischemic brain injury. This article summarizes experimental evidence that
      supports the role of excitatory amino acids, calcium, free radicals, nitric
      oxide, proinflammatory cytokines, and bioactive lipids. Specific vulnerabilities
      that distinguish the response of the immature brain from that of the mature brain
      are highlighted. These include increased susceptibility to excitotoxicity and
      free radical injury, greater tendency to apoptotic death, and heightened
      vulnerability of developing oligodendrocytes. Available supportive evidence from
      human studies is also included. Implications for clinical neuroprotective
      strategies are discussed.

PMID- 12516738
TI  - Chorioamnionitis and brain injury.
AB  - The limited available evidence supports a strong association of chorioamnionitis
      with neonatal encephalopathy and CP in the term infant. The association of
      chorioamnionitis with depressed Apgar scores or neonatal seizures and with CP is
      equivocal in the preterm infant. Different study results may be related to
      differences in study populations, perhaps specifically to differences in
      susceptibility by stages of neurologic development as well as differences in gene
      frequencies associated with inflammation and thrombophilia. We require further
      understanding of the normal roles of cytokines in brain development, pregnancy,
      and inflammatory homeostasis before clinical interventions directed at cytokines,
      their receptors, or the inflammatory process are considered.

PMID- 12516739
TI  - The effects of temperature on hypoxic-ischemic brain injury.
AB  - Over the past 15 years it has been recognized that the temperature of the brain
      has an important influence on the extent of brain injury that follows intervals
      of hypoxia-ischemia. Available data in animals and humans show that brain injury
      is worsened when fever is superimposed on an ischemic event. Furthermore, data in
      neonates and adults strongly suggest a neuroprotective role for modest
      hypothermia (temperature reductions of 1 to 6 degrees C) applied during or
      following ischemia or hypoxia-ischemia. This article provides an overview of the
      effects of brain temperature, including its role in the development of brain
      injury, mechanisms of brain injury which may be temperature sensitive, the
      regulation of brain temperature, thermal characteristics during brain cooling,
      and current clinical investigations that use temperature as a therapeutic
      modality.

PMID- 12516740
TI  - Hypoglycemic injury to the immature brain.
AB  - Despite the fact that hypoglycemia is an extremely common disorder of the
      newborn, consensus has been difficult to reach regarding definition, diagnosis,
      outcome, and treatment. With improved neuroradiologic techniques, such as MRI and
      PET scanning becoming increasingly available, studies to determine the
      correlation between hypoglycemia and outcome will help to clarify issues
      surrounding the effects of hypoglycemia on brain pathology. Long-term
      epidemiologic studies correlating the severity and duration of hypoglycemia with
      neurologic consequences are required, and can be complemented by appropriate
      parallel investigations in animal models of neonatal hypoglycemia.

PMID- 12516741
TI  - The postnatal management of the asphyxiated term infant.
AB  - Investigations in animal models of hypoxic-ischemic injury have not translated
      into clinical trials of success because of the complex pathology of hypoxic
      ischemic brain injury in neonates, the difficulty in defining the onset and
      duration and severity of the injury, the underlying predisposing disorders of the
      mothers or the infant, the side effects of many of the investigational drugs
      precluded clinical use, and many of the investigational agents interfered with
      only one step of the cascade of events that lead to brain injury. It is possible
      that a combination of therapeutic agents, including those that affect different
      levels of the cascade to cell death, will have the greatest neuroprotective
      effects. Modest hypothermia postpones secondary energy failure and can prolong
      the window while pharmacotherapeutic agents can be used. It is possible that in
      the future, sequential administration of agents or strategies that are initiated
      in the intrapartum period and continued postnatally will be the optimum method
      for treating infants who are at highest risk for brain injury following acute
      hypoxic-ischemic asphyxia.

PMID- 12516742
TI  - Cerebral infarctions in the fetus and neonate: maternal-placental-fetal
      considerations.
AB  - Historical data, clinical examination findings, and laboratory information must
      be integrated along a variable timeline that includes antepartum, intrapartum,
      and postnatal time periods when cerebral infarction can occur, in the context of
      the neonates genetic endowment. Genetic susceptibility or prenatal acquired
      vulnerabilities regarding stroke syndromes may set in motion a cascade of
      molecular pathways that ultimately cause or exacerbate brain injury when the
      vulnerable child experiences adverse medical conditions. The clinician must
      consider maternal, placental, and fetal conditions on which a stroke syndrome may
      be superimposed, with or without additional brain injury from other pathogenic
      mechanisms. Evaluation of fetal and neonatal cerebral infarction requires
      knowledge of mechanisms of brain injury that cross medical disciplines and may
      involve consultation with maternal/fetal specialists, placental and pediatric
      pathologists, neonatologists, geneticists, and other pediatric subspecialties.
      Comprehensive evaluations of survivors of cerebral infarction are needed to
      better understand structural and functional plasticity of the developing brain
      after a cerebrovascular event in the fetal and neonatal periods.

PMID- 12516743
TI  - Therapies administered to mothers at risk for preterm birth and
      neurodevelopmental outcome in their infants.
AB  - A decrease in the rate of preterm births and the prevention of prematurity
      associated neurodevelopmental morbidity are critical for the reduction of
      neurodevelopmental disability. Efforts to reduce the overall preterm delivery
      rate have been unsuccessful. Although progress has been achieved in the
      prevention of short-term neonatal morbidity over the past several decades, the
      majority of the improvements have resulted from improved neonatal care. Whether
      obstetric interventions can improve neurodevelopmental outcome is unknown. The
      ability to adequately assess obstetric interventions is hampered by the limited
      number of interventional studies that included long-term outcome assessment.
      Thus, it is incumbent upon ongoing and future interventional studies to consider
      long-term outcome assessment as a critical component of the overall evaluation of
      efficacy of obstetric therapies.

PMID- 12516745
TI  - Mechanisms of bilirubin toxicity: clinical implications.
AB  - The basic mechanism of kernicterus and bilirubin encephalopathy has not been
      unequivocally determined. Much knowledge has been gained about phenomena that
      contribute to bilirubin neurotoxicity, and this knowledge has implications for
      clinical practice. Conditions that impact on blood-brain barrier function,
      increase brain blood flow, or impact on bilirubin metabolism, including its
      transport in serum, should be avoided, if possible. Such conditions include drugs
      and drug stabilizers that compete with bilirubin binding to albumin, or that
      inhibit P-glycoprotein in the blood-brain barrier, prematurity/immaturity, and
      clinically significant illness in the infant that involves hemolysis, respiratory
      and metabolic acidosis, infection, asphyxia, hypoxia and (perhaps) hyperoxia, and
      hyperosmolality. If these conditions are not avoidable then there should be a
      more aggressive approach to the treatment of hyperbilirubinemia. The limits of
      tolerance for hyperbilirubinemia varies among neonates and there are no tools to
      determine with certainty when a particular infant is approaching the danger zone.
      Neurological symptoms in a jaundiced infant require extreme vigilance, and, in
      most cases, immediate intervention.

PMID- 12516744
TI  - Hemorrhagic-ischemic cerebral injury in the preterm infant: current concepts.
AB  - PV-IVH and adjacent white matter injury remains a significant problem in the
      premature infant. The potential mechanisms contributing to injury are complex and
      involve factors related to blood flow and its regulation, as well as cellular
      mediators including cytokines, free radical formation, and excitotoxin release.
      Although a reduction in the occurrence of severe IVH can be achieved with
      indomethacin, it does translate into long-term neurodevelopmental benefit. This
      reinforces the concept of a more diffuse injury to brain in sick premature
      infants than is apparent from the appearance of current neuroimaging techniques.

PMID- 12516746
TI  - Cognitive and behavioral deficits in premature graduates of intensive care.
AB  - A substantial number of VLBW graduates of intensive care develop cognitive and
      behavioral problems, even in the absence of neuroimaging abnormalities. Although
      this article has highlighted the potential, important, contributing role of
      medical and stressful, neonatal, environmental conditions to the development of
      these deficits, it is not all-encompassing, and there are additional prenatal
      (ie, in utero stress, drug exposure) and neonatal (ie, infectious) contributing
      factors. The long-term, outcome data presented in this article are pertinent to
      the more mature, VLBW infant, and it remains unclear and critically important to
      delineate the long-term, neurobehavioral outcome of those extremely low birth
      weight survivors born at the cutting limit of viability.

PMID- 12516747
TI  - Perinatal infections and brain injury: current treatment options.
AB  - Antimicrobial therapy can ameliorate infection and prevent long-term morbidity
      caused by several pathogens that infect the fetus and neonate. Ultimately,
      however, preventive strategies need to be developed and incorporated into routine
      preconceptional care. The future of prevention lies in immunizations, and if past
      and current successes with smallpox, polio, rubella, and measles vaccination
      programs are any indication, the future is bright for the developing fetus.

PMID- 12516748
TI  - Advances in postnatal neuroimaging: relevance to pathogenesis and treatment of
      brain injury.
AB  - The human brain is susceptible to a wide variety of insults. The permanent
      residua of these abnormalities are represented in dysfunction of one or more
      areas of neurodevelopment. A full understanding of normal brain development,
      mechanisms of brain injury, and consequences for subsequent brain development is
      required to determine which infants are at risk for neurodevelopmental handicap,
      and to monitor the effects of new treatments and management regimens designed to
      prevent these disabilities. Advanced magnetic resonance techniques, such as
      quantitative morphometric magnetic resonance techniques, diffusion-weighted
      magnetic resonance techniques, and magnetic resonance spectroscopy applied to the
      study of early human brain development have given us a better understanding of
      the pathophysiologic mechanisms of brain injury and its effects on subsequent
      brain development. Magnetic resonance imaging has provided an invaluable tool for
      the study of the fetal and newborn brain in vivo.

PMID- 12516749
TI  - Y chromosome genes and male infertility.
AB  - Normal spermatogenesis is a complex process that depends on many factors.
      Genetics plays a major role in many of these factors including providing a normal
      hormonal milieu, the development of the testis and ductal system, and control of
      the stepwise maturation of sperm in the testis. The Y chromosome plays a key role
      in testis determination and control of spermatogenesis. Understanding how these
      genes work together can elucidate of the exact cause of infertility in some
      patients once thought to have idiopathic infertility. It is not only important
      that patients understand the cause of their infertility. Using sperm from these
      men to attain pregnancies by assisted reproductive techniques will probably
      result in infertile male offspring. Additional consequences are currently unknown
      but are the topic of research investigations.

PMID- 12516750
TI  - Apoptosis: its importance in spermatogenic dysfunction.
AB  - Apoptosis, spontaneous programmed cell death, has recently generated great
      interest in several areas of investigation, including infertility. Selective
      sperm cell death also seems to be a component of normal spermatogenesis. A better
      understanding of this process may lead to the development of new strategies to
      treat intrinsic testicular failure.

PMID- 12516751
TI  - Current and future genetic screening for male infertility.
AB  - Although much of male infertility is currently unexplained, it is likely that
      underlying defects in critical genes or entire gene pathways are responsible.
      Because powerful technologies exist to bypass severe male-factor infertility,
      improving the diagnosis of genetic infertility is important for the infertile
      couple, not only to explain the problem but also to inform them of conditions
      potentially transmissible to offspring.

PMID- 12516752
TI  - Genetic counseling in translocations.
AB  - Advances in the treatment of male infertility-specifically intracytoplasmic sperm
      injection have now resulted in greater recognition of the clinical significance
      of genetic translocations. This article focuses on the different types of
      translocations (Robertsonian, reciprocal) as well as on the prevalence and
      incidence of translocations in infertile and other populations. The authors
      contrast theoretical and empiric meiotic segregation patterns in the different
      clinical settings of traditional prenatal genetic diagnosis and preimplantation
      genetic diagnosis. In particular, the significance of a higher prevalence of
      unbalanced blastomeres is discussed.

PMID- 12516753
TI  - The future of reproductive cellular engineering in male infertility.
AB  - Understanding of the pathophysiology of defective spermatogenesis, spermatozoa,
      and germ cell function must be advanced so that appropriate rational treatment,
      such as gene therapy, can be developed. Despite the dramatic advances in ART, one
      ultimate goal must be to develop treatment so that the couple can conceive
      naturally. Because such treatment will not be possible in all cases, a
      complementary step will be the ability to induce the production of haploid,
      functionally competent germ cells that can be used for ART. The achievement of
      these goals will be based on advances in many other disciplines. Whatever the
      future holds, it promises to be exciting.

PMID- 12516754
TI  - Role of oxidants in male infertility: rationale, significance, and treatment.
AB  - Interest in the physiologic and pathologic effects of ROS on male fertility is
      growing. The controlled generation of very low amounts of ROS seems to regulate
      the acquisition of sperm-fertilizing ability. High levels of ROS endanger sperm
      function and viability. Oxidative stress can arise as a consequence of excessive
      production of ROS or impaired antioxidant defense mechanisms in semen. Oxidative
      stress precipitates a range of pathologies that are thought to affect the male
      reproductive system. ROS-mediated peroxidative damage to the sperm plasma
      membrane may account for the defective sperm functions observed in a high
      proportion of infertility patients. High levels of ROS in semen have been
      correlated with reduced sperm motility and damage to sperm nuclear DNA.
      Determining the levels and the sources of excessive ROS production in human semen
      and precise evaluation of the scavenger system may be useful tools to develop
      therapeutic strategies for male infertility. Therapeutic interventions directed
      toward the isolation of mature spermatozoa by in vitro separation techniques may
      benefit infertile men in whom oxidative stress has a significant role.
      Nevertheless, this approach may be limited by the fact that the prolonged
      centrifugation involved in these procedures may enhance ROS production by
      spermatozoa. Clinical trials using antioxidants in vivo and in vitro have
      resulted in a major debate, and further research is required before one can be
      optimistic about a role for antioxidants in the treatment of infertile men. A
      double-blind, placebo-controlled study underway at the authors' center is
      evaluating the effects of treating infertile men with a combination of vitamins E
      and C after adjusting for all causes of controversy.

PMID- 12516755
TI  - Understanding the epidemiology of fertility treatments.
AB  - The science of statistics forms the basis of much of what urologists do and why.
      Understanding basic statistics is crucial to the appropriate interpretation of
      urologic studies. As valid as they are, the statistics taught in medical school
      represent only a small part of what computation can do for the urologist.
      Contemporary tools such as neural computation coupled with electronic technology
      that provides increasingly greater computational power in smaller space hold
      promise to integrate into the field of clinical urology as seamlessly as a
      ballpoint pen or cystoscope.

PMID- 12516756
TI  - Economics of treatments for male infertility.
AB  - Economic factors play a major role in the consideration of treatment options for
      male reproduction. This article has summarized the data and provided new insight
      into how patients, insurers, and populations evaluate competing therapies for
      male infertility. Many studies are difficult to interpret because of differing
      success rates and monetary bias. Future studies comparing line-by-line costs and
      reimbursements by independent sources may be the best way to evaluate different
      treatments.

PMID- 12516757
TI  - Ethical and legal issues in the use of related donors for therapeutic
      insemination.
AB  - Donor insemination involving family members can be complex. Although it may offer
      some advantages to the requesting individuals, to the donor, or to the family,
      related donation does raise a significant number of concerns. The specific
      circumstances of these requests should be considered carefully--in most cases
      more carefully than with anonymous sperm donation. Still, in the United States
      the freedom of couples or individuals to decide whether, when, and how to
      reproduce is highly valued. Respect for the autonomy of the involved family
      members would favor serious consideration of proposals for intrafamilial sperm
      donation, when all parties have freely consented to participate. Without
      exception, standards governing anonymous sperm donation should be followed in
      evaluating the proposed sperm donor for infectious and genetic diseases. The
      semen specimens should be frozen and quarantined for 180 days. In many cases, the
      6-month delay that results from this quarantine will discourage a couple from
      pursuing intrafamilial sperm donation. Adequate time is essential to assess these
      relationships when requested. Multiple visits to physicians, nurses, counselors,
      and lawyers may be necessary for a thorough assessment. Programs should require
      prospective participants, including recipients, donors, and partners of donors,
      to undergo psychologic counseling by a professional knowledgeable about gamete
      donation. Counselors should address issues such as emotional risks, potential
      impact on family relationships, the donor-recipient relationship, the future role
      of the donor in the offspring's life, and what information will be disclosed to
      the offspring. The process of obtaining informed consent from the requesting
      individuals, the donor, and, possibly, the donor's wife should involve a thorough
      discussion of potential risks to all parties. Clinicians should assure that the
      decision to be a sperm donor has been voulntary and free from manipulative and
      coercive influences. Financial incentives, including direct and indirect payment
      and inheritance, should not be so substantial that they become inducements that
      may lead the prospective donor to discount the emotional risk associated with the
      procedure. Legal counsel should be strongly encouraged to clarify issues of
      disclosure, rights, and duties, as well as the donor's relationship to the
      resulting offspring. Any possible changes in these issues in the event of divorce
      or death of requesting individuals should be addressed. In certain cases,
      requests should be immediately denied. Gametes from consanguineous relationships
      should never be used to initiate a pregnancy. Because of potential parental
      conflicts of interest, programs should not allow minors under the age of 18 years
      to donate sperm. The use of a family member may not be appropriate when sperm
      donation is chosen to prevent genetic diseases. Careful genetic counseling should
      be done before intrafamilial sperm donation is allowed in this situation. If,
      after careful consideration of the proposed arrangement, the physician chooses to
      facilitate the relationship, then all precautions should be taken to prevent
      medical, psychologic, and legal harm to the requesting couple or individual, the
      potential donor, and the prospective child. Programs that offer these
      arrangements should make every effort to obtain long-term follow up on the
      outcomes of these relationships, so that programs can provide more accurate
      information to families considering these relationships in the future. The
      physician or program should not feel obligated to agree to every request for
      intrafamilial sperm donation. When the assessment reveals consistent concerns
      about coercion of the prospective donor or about unhealthy family dynamics, the
      physician should feel free to deny these procedures. The physician should advise
      the requesting couple or individual to seek alternative methods, such as
      anonymous sperm donation, to conceive.

PMID- 12516758
TI  - Posthumous reproduction: current and future status.
AB  - Posthumous reproduction became possible with the technologies of sperm
      cryopreservation and ART. The legal and social status of children born as a
      result of these technologies continue to evolve. The proper disposition of
      unwanted stored gametes and embryos remains unknown. Physicians are increasingly
      asked to make quick judgments on posthumous gamete retrieval. The procedures for
      gamete harvest are technically simple; however, one must carefully select cases
      with definitive prior intent to have children. There is a need for standardized
      legal protocols to protect the physician and the patient. The physician must use
      sound judgment and comply with accepted standards, when present, before
      performing any service for posthumous sperm retrieval and reproduction.

PMID- 12516759
TI  - Comprehensive office evaluation in the new millennium.
AB  - The success of a comprehensive office-based evaluation of male-factor infertility
      depends on the physician's thorough understanding of risk assessment in the
      history, identification of pertinent physical examination findings, and correct
      assessment of laboratory data. Office-based ultrasonographic techniques have
      already increased the urologist's ability to visualize suspected anatomic
      abnormalities, and the use of functional tests of sperm has given greater depth
      to the limited, but essential, prognostic capabilities of the routine semen
      analysis.

PMID- 12516760
TI  - The diagnosis and treatment of the azoospermic patient in the age of
      intracytoplasmic sperm injection.
AB  - Microsurgical reconstruction remains the treatment of choice for men with
      reconstructable obstructive azoospermia. Sperm retrieval techniques performed
      with ICSI are highly effective for men in whom reconstruction is not feasible. In
      men with nonobstructive azoospermia, the optimization of spermatogenesis with
      hormonal therapy and, when appropriate, microsurgical varicocelectomy can result
      in the appearance of adequate sperm in the ejaculate for ICSI. In men with
      persistent nonobstructive azoospermia, TESE with ICSI has provided encouraging
      results. Caution must be used when this ART is applied in couples in whom genetic
      aberrations are detected given certain inheritance of these anomalies, as the
      genetic consequences of this procedure have not been thoroughly elucidated. Just
      as the possibility of ICSI was thought to be inconceivable several decades ago,
      the advent of future sentinel discoveries will present the possibility for
      realization of achievements that now seem incredulous.

PMID- 12516761
TI  - Predictive parameters for microsurgical reconstruction.
AB  - Microsurgical techniques have made vasectomy reversal a realistic option for the
      restoration of fertility in a man who has previously undergone vasectomy. Factors
      that can affect the success of these procedures may become known preoperatively
      and intraoperatively; this article reviews each of those factors.

PMID- 12516762
TI  - Varicocele: current concepts in pathophysiology, diagnosis, and treatment.
AB  - Although significant advances have been made in the understanding of varicoceles,
      a clear pathophysiologic mechanism remains elusive. Most likely, a varicocele is
      the result of a multifactorial process. Appreciation of the complex venous
      drainage of the testis remains a key to maximizing the chances for treatment
      success. Likewise, the advent of microsurgical repair has minimized
      complications. Fortunately, times have improved since the early nineteenth
      century, when the French surgeon Delpech (1772-1832) was killed by a disgruntled
      patient on whom he had performed a varicocele repair.

PMID- 12516763
TI  - Diagnosis and treatment of ejaculatory dysfunction.
AB  - The normal ejaculatory process requires complex coordination and integration of
      neurologic, physiologic, anatomic, and psychologic events. An understanding of
      these processes is critical to evaluate properly and manage patients with
      ejaculatory dysfunction. With the advent of improved techniques to treat
      patients, some men with ejaculatory dysfunction are being offered the opportunity
      to reproduce. Further research on the ejaculatory process and associated
      dysfunctional states should continue to improve treatment for patients presenting
      with ejaculatory disorders.

PMID- 12516764
TI  - A new look at the medical management of infertility.
AB  - Effective therapies are available for the treatment of infertility owing to
      specific causes. Most hormonal imbalances can be readily identified and
      successfully treated. The treatment of men with unexplained idiopathic
      infertility remains difficult. The availability of a multitude of agents ranging
      from hormones to nutritional supplements emphasizes the fact that none are
      consistently effective. There is no good way to predict which patients will
      respond to a specific treatment. Idiopathic infertility may result from multiple
      discrete defects in sperm generation and maturation that are as yet unidentified.
      A better understanding of these defects will yield more effective treatment
      options and appropriate triage of patients to specific therapeutic regimens.
      Assisted reproductive techniques remain an option for patients with idiopathic
      male infertility; however, they are expensive and treat the female partner for a
      male problem. Multiple gestations and other complications are not infrequent.
      Initial management should be directed at improving the quality of semen to
      facilitate natural conception. Specific abnormalities should be corrected. If
      empiric pharmacologic therapy is to be used, treatment should last at least 3 to
      6 months to incorporate a full 74-day spermatogenic cycle. The infertile couple
      should be advised of the inconsistent response to therapy and the low conception
      rate that may follow when compared with the results of ART. When empiric therapy
      is decided upon, antiestrogens may be used and are effective in a subset of
      patients. The authors prefer to use clomiphene citrate, 25 mg per day. The dose
      may be increased to 50 or 75 mg to raise testosterone levels to the upper normal
      range. Lack of a significant improvement in semen parameters or of a pregnancy
      after a 3- to 6-month treatment period may be an indication to proceed with ART.

PMID- 12516765
TI  - Common medications and drugs: how they affect male fertility.
AB  - Numerous drugs and medications have been shown to have adverse effects on male
      fertility, acting through diverse mechanisms. These drugs are summarized in Table
      2. Mechanisms of impaired fertility include direct effects on germ cells or their
      supporting cells, effects on the delicately balanced HPG axis, effects on
      erectile or ejaculatory function, and effects on libido. In a thorough fertility
      evaluation of the male partner, the physician should determine what medication
      the patient is taking and his social habits involving alcohol consumption,
      tobacco, and recreational drug use. Most adverse effects from drugs and
      medications can be reversed by simply discontinuing the offending agents;
      however, in some instances, such as chemotherapeutic regimens, the medications
      cannot be discontinued, and pretreatment sperm cryopreservation remains critical.
      It is essential for urologists treating infertile men to be familiar with the
      more commonly encountered drugs and medications that may affect the potential for
      fertility.

PMID- 12516767
TI  - What the urologist should know about the female infertility evaluation.
AB  - As childbirth is delayed and divorce rates remain high, urologists will continue
      to see more and more infertile couples. It is imperative that urologists
      understand at least the basic aspects of the female evaluation. Fundamental
      information can be obtained from a simple, directed history. Risk factors for
      female infertility can be identified in a matter of minutes, and the reproductive
      endocrinologist can then carry out a complete female evaluation simultaneously
      with the male evaluation. Most female infertility problems can be classified as
      ovulatory, anatomic, or cervical. Signs of decreasing ovarian reserve with age
      can be ascertained easily with a history and perhaps the determination of a day-3
      serum FSH level. Finally, a basic understanding of the female evaluation allows
      meaningful discourse between the urologist and the reproductive endocrinologist,
      leading to a more effective treatment plan for the infertile couple.

PMID- 12516766
TI  - Androgen deficiency in the aging male: when, who, and how to investigate and
      treat.
AB  - Androgen deficiency in the aging male (ADAM), also known as andropause, affects
      an estimated 1 in 200 men. The abnormally low levels of testosterone in these men
      can usually be managed with androgen supplementation therapy. Because a large
      proportion of urologic patients are men at or beyond middle age, urologists
      should be familiar with ADAM, its clinical manifestations, the rational approach
      to its diagnosis and treatment, and the consequences of treatment. Equally
      important is responsibility for the patient's monitoring, because prolonged
      androgen replacement therapy can be associated with significant complications,
      particularly in the prostrate.

PMID- 12516768
TI  - Role of internalization in the pathogenicity of Shiga toxin-producing Escherichia
      coli infection in a gnotobiotic murine model.
AB  - We investigated the role of bacterial internalization in the killing caused by
      Shiga toxin-producing Escherichia coli (STEC) infection using a gnotobiotic
      murine model. A high number of internalized STEC was found in the colonic
      epithelial cells of STEC-infected mice by both an ex vivo assay and transmission
      electron microscopy. Most of these mice were killed within 10 days after
      infection. However, the implantation of lactic acid bacteria in such mice before
      infection markedly decreased the number of internalized STECs and also completely
      protected these hosts from killing by a STEC infection. The inhibition of such
      internalization by immunoglobulin also prevented the hosts from being killed. The
      Shiga toxin levels in these hosts indicated an inhibition of the penetration of
      Shiga toxins produced in the colon to the underlying tissue. These results
      suggested that the internalization plays an important role in the pathogenicity
      caused by STEC infection in a gnotobiotic murine model.

PMID- 12516769
TI  - Characterization of monoclonal antibody reacting exclusively against
      intracellular Orientia tsutsugamushi.
AB  - Intracellular bacteria often change the expression of their genes in order to
      adapt to new environmental conditions. Here we describe a monoclonal antibody
      (MAb) that reacts exclusively against intracellular Orientia tsutsugamushi.
      Although MAb applied to the 56-kDa protein, a major outer membrane protein,
      reacted against a large number of bacteria that had attached to host cells at the
      early stage of infection, M686-13 reacted against only a minor portion of the
      attached bacteria. In the later stage of the intracellular growth cycle, both
      antibodies showed identical staining patterns by double immunofluorescent
      staining. These results suggest that M686-13 reacted to an epitope or a protein
      that had probably been expressed during the intracellular growth cycle and
      rapidly diluted or degraded upon release into the extracellular environment.
      Although its molecular characteristics remain unknown, the reactive antigen may
      prove to be a novel developmental antigen and this MAb could be used as reagent
      for the staining of viable O. tsutsugamushi.

PMID- 12516770
TI  - Antimicrobial activity and stability to proteolysis of small linear cationic
      peptides with D-amino acid substitutions.
AB  - Antimicrobial peptides contribute to innate host defense against a number of
      bacteria and fungal pathogens. Some of antimicrobial synthetic peptides were
      systemically administered in vivo; however, effective protection has so far not
      been obtained because the effective dose of peptides in vivo seems to be very
      high, often close to the toxic level against the host. Alternatively, peptides
      administered in vivo may be degraded by certain proteases present in serum. In
      this study, D-amino acids were substituted for the L-amino acids of antimicrobial
      peptides to circumvent these problems. Initially a peptide (L-peptide) rich in
      five arginine residues and consisting of an 11-amino acid peptide (residues 32
      42) of human granulysin was synthesized. Subsequently, the L-amino acids of the
      11-amino acid peptide were replaced partially (D-peptide) or wholly (AD-peptide)
      with D-amino acids. Activity and stability to proteolysis, in particular, in the
      serum of antimicrobial peptides with D-amino acid substitutions were examined.
      Peptides with D-amino acid substitutions were found to lyse bacteria as
      efficiently as their all-L-amino acid parent, L-peptide. In addition, the peptide
      composed of L-amino acids was susceptible to trypsin, whereas peptides containing
      D-amino acid substitutions were highly stable to trypsin treatment. Similarly,
      the peptide consisting of L-amino acids alone was also susceptible to fetal calf
      serum (FCS), however, protease inhibitors restored the lowered antimicrobial
      activity of the FCS-incubated peptide. Thus, D-amino acid substitutions can make
      antimicrobial peptides resistant to proteolysis, suggesting that the
      antimicrobial peptides consisting of D-amino acids are potential candidates for
      clinical therapeutic use.

PMID- 12516771
TI  - Interferon regulatory factor 1 in mycobacterial infection.
AB  - In order to understand the role of IRF-1 in the development of murine
      tuberculosis in vivo, IRF-1 knockout mice were infected with Mycobacterium
      tuberculosis by placing them in the exposure chamber of an airborne infection
      apparatus. These knockout mice developed multifocal necrotic lesions in the lung,
      liver and spleen tissues and died of disseminated tuberculosis within 43 days of
      infection. Compared with the levels in wild-type mice, the pulmonary inducible NO
      synthase (iNOS) mRNA expression level was significantly lower, but IL-18 and IL-6
      mRNA levels were higher. There was no statistically significant difference in the
      expression of IFN-gamma and TNF-alpha mRNA between the IRF-1 knockout and wild
      type mice. IRF-1 is indirectly responsible for iNOS mRNA expression and plays an
      important role in the pathogenesis of murine tuberculosis.

PMID- 12516772
TI  - Use of immunoglobulin enriched bovine colostrum against oral challenge with
      enterohaemorrhagic Escherichia coli O157:H7 in mice.
AB  - An immunoglobulin enriched bovine colostrum preparation, IMMULAC (New Zealand
      Dairy Group, Cambridge, New Zealand), contains antibodies against various
      bacterial antigens. In the present study, we investigated the protective effects
      of a commercial bovine colostrum preparation against infections with
      enterohaemorrhagic Escherichia coli (EHEC) O157:H7 in a murine model. Balb/c mice
      were given drinking water containing streptomycin for 3 days before and following
      oral challenge with streptomycin-resistant EHEC O157:H7 strain (O157-SM(R)). In
      mice pretreated with streptomycin, EHEC O157:H7 maintained stable levels of
      bacterial colonization in the intestines for the 3-week experimental time period.
      Oral administration of colostrum resulted in rapid decrease in the bacteria
      numbers compared with administration of skim-milk. Colostrum showed no direct in
      vitro bactericidal properties against either EHEC O157:H7. When sections prepared
      from cecum walls of streptomycin-pretreated mice were incubated in vitro with
      EHEC O157:H7, the colostrum significantly prevented the attachment of the
      organisms to the sections when compared with skim-milk. These results indicate
      that oral administration of bovine colostrum effectively protects mice against
      food-borne infections by inhibiting bacterial attachment to the intestinal mucous
      membrane, colonization and growth in the intestinal tract.

PMID- 12516773
TI  - Molecular fingerprinting of isoniazid-resistant Mycobacterium tuberculosis
      isolates from chest diseases hospital in Kuwait.
AB  - Touchdown double-repetitive-element-PCR (DRE-PCR) was carried out for typing 38
      consecutive isoniazid-resistant Mycobacterium tuberculosis strains isolated at
      Chest Diseases Hospital, Kuwait, during 1998-2000. The polymorphism at codon 463
      in the katG gene was also determined and correlated with genotypic relationships
      among the isolates. The isolates exhibited 21 distinct patterns in DRE-PCR.
      Nearly half of the isolates (18 of 38) exhibited unique patterns. Majority of
      isolates (16 of 20) yielding multiple DNA fragments in DRE-PCR were unique
      strains while most of the isolates (16 of 18) yielding a single DNA fragment in
      DRE-PCR clustered together. The prevalence of L463 in the katG gene was much
      higher in isolates from Middle Eastern (mostly Kuwaiti) patients than is reported
      for this ethnic group. The data indicate the possibility of some strains of South
      Asian/Southeast Asian origin spreading among local populations.

PMID- 12516774
TI  - Lethal factor to mice produced by Escherichia coli isolated from chickens with
      swollen head syndrome.
AB  - A lethal toxin similar to Bacillus cererus lethal toxin was detected in the
      culture supernatants of Escherichia coli isolated from chickens with swollen head
      syndrome. The lethal activity was heat-labile, protease-sensitive and killed mice
      within 10 min. The light microscopy of the histopathological studies revealed
      that the principal organ affected by this toxin was the lung but the liver and
      kidneys also showed lesions. The relevance of this lethal activity from E. coli
      remains to be determined.

PMID- 12516775
TI  - Monoclonal antibody to shiga toxin 1, which blocks receptor binding and
      neutralizes cytotoxicity.
AB  - A monoclonal antibody, 5-5B, which neutralizes Shiga toxin 1 (Stx1) cytotoxicity
      of Escherichia coli, was constructed. An epitope analysis indicated that Asn55 in
      Stx1 B subunit was an important residue. This result and our previous results
      using an anti-Stx2 monoclonal antibody indicate that the region around the
      cysteine residue of the disulfide bond might be important for the neutralization
      of Stx cytotoxicity, making it a potential vaccination candidate.

PMID- 12516776
TI  - Stimulation of the secretion of pro-inflammatory cytokines by Bifidobacterium
      strains.
AB  - To characterize the ability of bifidobacteria to affect the production of
      macrophage-derived cytokines, a murine macrophage-like cell line, J774.1, was
      cultured in the presence of 27 strains of heat-inactivated bifidobacteria.
      Bifidobacterium adolescentis and B. longum, known as adult-type bifidobacteria,
      induced significantly more pro-inflammatory cytokine secretion, IL-12 and TNF
      alpha, by J774.1 cells, than did the infant-type bifidobacteria, B. bifidum, B.
      breve, and B. infantis (P<0.01). In contrast, B. adolescentis did not stimulate
      the production of anti-inflammatory IL-10 from J774.1 cells as the other tested
      bacteria did. The results suggest that the adult-type bifidobacteria, especially
      B. adolescentis, may be more potent to amplify but less able to down-regulate the
      inflammatory response.

PMID- 12516777
TI  - Human immunodeficiency virus type 1 subtype C exhibits higher transactivation
      activity of Tat than subtypes B and E.
AB  - Although human immunodeficiency virus type 1 (HIV-1) subtypes C and E are
      expanding faster and seem to be of greater global significance than HIV-1 subtype
      B, there is only little information about Tat activity of such non-B subtypes.
      Here, we showed evidence that subtype C Tat exhibits higher transcriptional
      activity from the HIV-1 long-terminal repeat (LTR) in a human T-cell line,
      compared with subtypes B and E. This higher activity of subtype C Tat was not due
      to the LTR, but to the Tat sequence variability. We examined three candidate
      regions with sequence for the higher activity of subtype C Tat, such as the
      cysteine-rich motif, the basic domain, and the 2nd exon. The results showed that
      the variation in subtype C Tat at two amino acid residues, Ser57 and Glu63 in
      stead of Arg57 and Gln63 in subtypes B and E, within and close to the basic
      domain were involved in the higher activity of subtype C Tat. This variation did
      not affect its nuclear localization activity. Thus, there may be a significant
      advantage for the high Tat activity on subtype C replication.

PMID- 12516778
TI  - Complete sequence analyses of enterovirus 71 strains from fatal and non-fatal
      cases of the hand, foot and mouth disease outbreak in Singapore (2000).
AB  - Enterovirus 71 (EV71) is a major aetiological agent of hand, foot and mouth
      disease (HFMD). In recent years, several outbreaks in East Asia were associated
      with neurological complications and numerous deaths. An outbreak in Singapore in
      October 2000 afflicted thousands of children, resulting in four fatal cases from
      three of whom EV71 was isolated. The genomes of two representative EV71 strains
      isolated from a fatal case and a surviving patient were completely sequenced, and
      their nucleotide and amino acid sequences compared with known EV71 strains. The
      two outbreak strains were classified under genogroup B, together with those
      previously isolated in Singapore, Malaysia and Japan. Comparative sequence
      analysis of the two Singapore strains revealed 99% nucleotide similarity, while
      their deduced amino acid sequences were almost identical except for residue 1506
      in the 3A non-structural region. Given that the outbreak involved closely related
      genetic variants of EV71, the broad spectrum of disease severity may be
      attributed to critical factors such as varying viral inoculation doses or
      differing host immune responses following infection, but is less likely to be due
      to the emergence of EV71 strains with heightened virulence.

PMID- 12516779
TI  - Double-stranded nef RNA interferes with human immunodeficiency virus type 1
      replication.
AB  - RNA interference (RNAi) has been reported to be post-transcriptional gene
      silencing (PTGS) by approximately 500 nucleotide-(nt)-long double-stranded (ds)
      RNA that specifically targets homologous sequences of messenger RNA. In this
      report, we describe inhibition of HIV-1 transcription by synthetic dsRNAs
      constructed with mutated nef genes (nef dsRNAs) derived from long-term non
      progressors (LTNPs) using cotransfection of the target gene-expressing plasmid
      and dsRNA. The effects of nef dsRNAs were examined with luciferase (Luc) reporter
      which is combined with the HIV-1 (SF2) LTR in persistently HIV-1-infected T cell
      and macrophage cell lines. At 48 hr, a defective nef dsRNA (556 nt) suppressed
      Luc activity more potently than did SF2 full-length nef dsRNA (744 nt),
      suggesting that approximately 500 nt-long nef dsRNA could interfere with the HIV
      1 transcription.

PMID- 12516780
TI  - Nobel Lecture. Yeast and cancer.
AB  - The discovery of genes that control cell division in yeast, and their relation to
      cancer, is reviewed.

PMID- 12516781
TI  - Involvement of protein tyrosine kinases and phosphatases in uptake and
      intracellular replication of virulent and avirulent Leishmania donovani
      promastigotes in mouse macrophage cells.
AB  - In this study we show that protein tyrosine kinases (PTKs) and also protein
      tyrosine phosphatases are involved in the uptake of virulent and avirulent
      Leishmania donovani promastigotes by macrophage cells. Protein tyrosine kinase
      inhibitors such as genistein or tyrphostin 25 decrease parasite uptake in a dose
      dependent manner. Addition of sodium orthovanadate, a protein tyrosine
      phosphatase inhibitor, prior to infection significantly increases parasite
      internalization. A similar uptake profile was observed with both virulent and
      avirulent L. donovani promastigotes. Treatment of macrophages with cytochalasin
      B, an inhibitor of actin polymerization prevents promastigote uptake, indicating
      that a tyrosine kinase induced actin polymerization signal may be necessary for
      the entry of the parasites. In contrast, neither genistein nor tyrphostin
      significantly reduce intracellular replication of this pathogen or nitric oxide
      production, suggesting that the PTK-mediated signal is not related to the
      ultimate virulence mechanism associated with intracellular replication of this
      pathogen. These data collectively suggest that protein tyrosine kinase mediated
      entry of L. donovani promastigotes into macrophages is not a virulence-associated
      event.

PMID- 12516782
TI  - The 78 kDa glucose-regulated protein (GRP78/BIP) is expressed on the cell
      membrane, is released into cell culture medium and is also present in human
      peripheral circulation.
AB  - In human rabdomiosarcoma cells (TE671/RD) chronic exposure to 500 nM thapsigargin
      (a powerful inhibitor of the endoplasmic reticulum Ca2+-ATPases) resulted in the
      induction of the stress protein GRP78/BIP. Making use of the surface
      biotinylation method, followed by the isolation of the GRP78 using ATP-agarose
      affinity chromatography, it was found that a fraction of the thapsigargin-induced
      GRP78 is expressed on the cell surface. The presence of GRP78 on the membrane of
      thapsigargin-treated cells was confirmed by fractionation of cell lysates into a
      soluble and a membrane fraction, followed by Western blot analysis with an anti
      GRP78 antibody. It was also found that conspicuous amounts of GRP78 are present
      in the culture medium collected from thapsigargin-treated cultures. This
      extracellular GRP78 originates mostly by an active release from intact cells and
      does not result solely from the leakage of proteins from dead cells. Moreover,
      small amounts of circulating, free GRP78 and naturally-occurring anti-GRP78
      autoantibodies were detected in the peripheral circulation of healthy human
      individuals.

PMID- 12516783
TI  - F0 cysteine, bCys21, in the Escherichia coli ATP synthase is involved in
      regulation of potassium uptake and molecular hydrogen production in anaerobic
      conditions.
AB  - The single cysteine in the b subunit of the membranous F0 sector and the 19
      cysteines in extramembranous F1 sector of the Escherichia coli ATP synthase were
      replaced by alanine. When cells were grown under anaerobic conditions on glucose,
      the kcat for ATP hydrolysis of membrane vesicles containing the bCys21Ala mutant
      enzyme, but not enzymes with other cysteine replacements, was lower, while ATP
      driven H+ pumping was unchanged. However, the ATP-dependent increase in the
      number of accessible thiol groups in membrane vesicles was negated. Furthermore,
      K+ uptake and molecular hydrogen production by whole cells and protoplasts was
      greatly decreased. These results indicate a role for the F0 subunit bCys21 in the
      functionality of F0F1 and coupling to other membranous activities under
      fermentative conditions.

PMID- 12516784
TI  - Ligand binding characteristics and aggregation behavior of purified cow's milk
      folate binding protein depends on the presence of amphiphatic substances
      including cholesterol, phospholipids, and synthetic detergents.
AB  - Folate binding protein was purified from cow's milk by a combination of cation
      exchange chromatography and methotrexate-AH-sepharose affinity chromatography.
      Dilution of the preparation to concentrations of protein less than 10 nM resulted
      in drastic changes of radioligand (folate) binding characteristics, i.e., a
      decrease in binding affinity with a change from upward to downward convex
      Scatchard plots and increased ligand dissociation combined with appearance of
      weak-affinity aggregated forms of the binding protein on gel filtration. These
      findings, consistent with a model predicting dimerization between unliganded and
      liganded monomers, were reversed in the presence of material eluted from the
      affinity column after adsorption of the protein(cofactor) or cholesterol,
      phospholipids, and synthetic detergents. The latter amphiphatic substances form
      micelles and lipid bilayers which could separate hydrophobic unliganded monomers
      from hydrophilic liganded monomers in the surrounding aqueous medium and thereby
      prevent association between these monomeric forms prevailing at low
      concentrations of the protein. Our data have some bearings on studies which show
      that cholesterol and phospholipids are necessary for the clustering of folate
      receptors in the cell membrane; a process required for optimum receptor function
      and internalization of folate.

PMID- 12516785
TI  - A combination of cation exchange and ligand-affinity chromatography for
      purification of two molecular species of the folate binding protein in human
      milk, one equipped with a hydrophobic glycosyl phosphatidylinositol tail:
      characterization of hydrophobicity and electrical charge.
AB  - Cation exchange chromatography combined with ligand (methotrexate) affinity
      chromatography on a column desorbed with a pH-gradient was used for separation
      and large scale purification of two folate binding proteins in human milk. One of
      the proteins, which had a molecular size of 27 kDa on gel filtration and eluted
      from the affinity column at pH 5-6 was a cleavage product of a 100 kDa protein
      eluted at pH 3-4 as evidenced by identical N-terminal amino acid sequences and a
      reduction in the molecular size of the latter protein to 27 kDa after cleavage of
      its hydrophobic glycosylphosphatidyl-inositol tail that inserts into Triton X-100
      micelles. Chromatofocusing showed that both proteins possessed multiple
      isoelectric points within the pH range 7-9. The 100 kDa protein exhibited a high
      affinity to hydrophobic interaction chromatographic gels, whereas this was only
      the case with unliganded forms of the 27 kDa protein indicative of a decrease in
      the hydrophobicity of the protein after ligand binding.

PMID- 12516786
TI  - Ligand binding characteristics of two molecular forms, one equipped with a
      hydrophobic glycosyl phosphatidylinositol tail, of the folate binding protein
      purified from human milk.
AB  - Two molecular forms of the folate binding protein were isolated and purified from
      human milk by a combination of cation exchange- and affinity chromatography. One
      protein (27 kDa) was a cleavage product of the other 100 kDa protein as evidenced
      by N-terminal amino acid sequence homology and a reduction in the molecular size
      of the latter protein to 27 kDa after cleavage of its hydrophobic
      glycosylphosphatidylinositol tail by phosphatidylinositol-specific phospholipase
      C. High-affinity binding of [3H]folate was characterized by upward convex
      Scatchard plots and increasing ligand binding affinity with decreasing
      concentrations of both proteins. Downward convex Scatchard plots and binding
      affinities showing no dependence on the protein concentration were, however,
      observed in highly diluted solutions of both proteins. Radioligand binding was
      inhibited by folate analogs, and dissociation of radioligand was slow at pH 7.4
      but rapid and complete at pH 5.0 and 3.5. Ligand binding quenched the tryptophan
      fluorescence of the 27 kDa protein suggesting that tryptophan is present at the
      binding site and/or ligand binding induces a conformation change that affects
      tryptophan environment in the protein. The 27 kDa protein representing soluble
      folate binding protein exhibited a greater affinity for ligand binding than the
      100 kDa protein which possesses a hydrophobic tail identical to the one that
      anchors the folate receptor to the cell membrane.

PMID- 12516787
TI  - Six years and counting: the NIH-funded Clinical Research Center of Hawaii.
AB  - The CRC was developed in 1995 to make Hawaii a site of innovative, progressive
      research. Since then, the numbers of researchers and publications supported by
      the CRC have increased. In the next several years, the CRC will expand further
      into Hawaii's research community and apply for GCRC status, a strategy that will
      attract even more resources and investigators to JABSOM.

PMID- 12516788
TI  - Adverse effects of superactivated charcoal administered to healthy volunteers.
AB  - OBJECTIVES: Activated charcoal is frequently administered to drug overdose
      patients, who may experience nausea and vomiting secondary to the drug overdose.
      Drinking a charcoal slurry orally may be difficult for them necessitating a
      gastric tube. The purpose of this study is to report the frequency of adverse
      effects from oral superactivated charcoal (SAC) given to healthy volunteers.
      METHODS: Healthy adult study subject volunteers were given a single 2000 mg
      (first 13 subjects) or 3000 mg (remaining 35 subjects) dose of acetaminophen.
      Subjects were randomized to receive no charcoal (ctrl) or 75 grams of SAC
      administered orally in a slurry 3 hours following the acetaminophen dose. The
      adverse effects of both groups were recorded and compared. RESULTS: There were 48
      study subject runs. The mean age was 27.4 years (SD6.5). SAC was administered to
      24 subjects. Adverse effect rates were as follows (*one-tail p < 0.05): black
      stool* (SAC 22/ 24, ctrl 0), constipation or abdominal fullness* (SAC 12/24, ctrl
      0), nausea* (SAC 5/24, ctrl 0), vomiting (SAC 2/24, ctrl 0), diarrhea (SAC 2/24,
      ctrl 0), anal irritation (SAC 2/24, ctrl 0), drowsiness/fatigue (SAC 2/24, ctrl
      3/24), dizziness/lightheadedness (SAC 0, ctrl 1/24), headache (SAC 4/24, ctrl 0).
      7 of 24 SAC subjects and 20 of 24 ctrl subjects experienced no adverse effects at
      all* (other than black stools for the SAC subjects). Acetaminophen may have been
      blunted some adverse effects. Two SAC subjects could not finish the charcoal. For
      the 22 subjects who finished the charcoal, SAC consumption took a mean of 10.9
      minutes (SD 11.8, range 1 to 50 minutes). Thirteen subjects finished it in 7
      minutes or less. Six subjects took 19 minutes or longer to finish it. The 12
      heavier subjects (> 71kg) completed SAC consumption significantly faster than the
      12 lighter subjects (18.7 vs 7.8 minutes, p = 0.04, single sided). This
      comparison included the two subjects (both lighter) who did not finish SAC
      consumption, so this difference was no longer significant when these two subjects
      were removed. CONCLUSIONS: Superactivated charcoal consumption is associated with
      significant adverse effects in some healthy volunteers, which may impede a drug
      overdose patient's ability to willingly drink charcoal slurry in a reasonable
      period of time.

PMID- 12516789
TI  - 28 year-old man with thrombophilia and hypercalcemia.

PMID- 12516790
TI  - The Student Development Program: facilitating student success at the John A.
      Burns School of Medicine.

PMID- 12516791
TI  - Improved methods to stage cancer: the evolving role of sentinel node staging in
      solid malignancies.

PMID- 12516792
TI  - Children at risk.

PMID- 12516793
TI  - Specialization.

PMID- 12516794
TI  - Mentoring.

PMID- 12516795
TI  - The influence of head movement on the accuracy of a rapid pointing task.
AB  - BACKGROUND: Eye-hand coordination contributes to sports performance. The positive
      effect of head movement on the accuracy of eye-hand coordination of some subjects
      has been demonstrated for self-paced or single tasks, but not for rapid,
      repetititive tasks, such as those sometimes required in sports. The purpose of
      this study was to determine whether head movement is detrimental to performance
      of a rapid, repetitive pointing task. METHODS: Pointing accuracy and speed were
      tested using the AcuVision 1000 trainer, a device designed to assess and train
      eye-hand coordination. Twenty-six subjects participated. In one trial, subjects
      were told to turn their heads toward the targets as they pointed at them. In a
      second trial, subjects were told to keep their heads stationary as they pointed
      at the targets. The order of the trials was counter-balanced and subjects were
      randomly assigned to one of the orders. RESULTS: Pointing accuracy was
      significantly greater in the head movement trial than in the no head movement
      trial. CONCLUSIONS: Head movement increased the accuracy of this rapid task. Head
      movement probably allows more-accurate encoding of target position by maintaining
      the eyes in less-eccentric positions of gaze.

PMID- 12516796
TI  - The use of contact lenses by U.S. civilian pilots.
AB  - BACKGROUND: Since 1976, the use of contact lenses by civilian pilots has been
      permitted to correct distant vision for obtaining a Federal Aviation
      Administration (FAA) aeromedical certificate. This study examined the civil
      airman population's experience with contact lens use for a 30-year period (1967
      to 1997). METHODS: Population totals for airmen who carried pathology codes 161
      (contact lens) and 158 (orthokeratology) from January 1, 1967 through December
      31, 1997 were used to calculate prevalence rates by class of medical certificate
      and age. The National Transportation Safety Board and FAA databases were queried
      to determine if contact lens use had contributed to aviation mishaps. RESULTS:
      The prevalence of contact lens use grew faster for first-class medical
      certificate holders and airmen > or = 40 years of age during the period. The
      frequency of airmen with orthokeratology increased by 23 times in a 10-year
      period. Reports from five aviation accidents and one incident suggested that
      contact lens use was a contributing factor in these mishaps. CONCLUSIONS:
      Professional pilots and older airmen were found to be more inclined to use
      contact lenses. The increasing use of contact lenses and the rapid changes in
      contact lens technology warrant continued monitoring to ensure aviation safety.

PMID- 12516797
TI  - Pupil block glaucoma from traumatic vitreous prolapse in a patient with posterior
      chamber lens implantation.
AB  - BACKGROUND: Angle closure secondary to pupil block is an entity known to occur in
      aphakic and pseudophakic patients. In aphakic patients, typically the cause of
      the pupil block is vitreous prolapse (aphakic pupil block). In pseudophakic
      patients, the typical cause of the pupil block is an anterior chamber lens
      implant, often in the absence of an iridectomy (pseudophakic pupil block).
      Rarely, a hybrid of these two conditions can occur, in which vitreous prolapse
      causes a pupil block in a pseudophakic patient with a posterior chamber lens
      implant. METHODS: The case presented is that of an elderly pseudophakic man with
      a posterior chamber lens implant who experienced ocular trauma, and who
      subsequently also experienced a ruptured posterior capsule with resultant
      vitreous prolapse and pupil block angle closure. Key diagnostic features are
      presented, as well as patient-specific management for this uncommon condition.
      CONCLUSIONS: While diagnosis and management of acute primary angle closure are
      well-known and reported, acute secondary angle closure is not as well reported.
      It is imperative to understand the mechanism of angle closure, as this properly
      delineates the management plan. Use of management plans appropriate to acute
      primary angle closure with pupil block (the use of miotics) could potentially
      have disastrous consequences in cases of secondary angle closure from vitreous
      prolapse.

PMID- 12516798
TI  - A 13-year followup of a case of Wallenberg's syndrome: first-person account and
      ocular motor abnormalities.
AB  - BACKGROUND: We present a 13-year followup of a case of Wallenberg's syndrome,
      including a first-person account and ocular motor abnormalities. METHODS:
      Objective infrared eye-tracking systems were used to record horizontal and
      vertical eye movements binocularly under a variety of conditions. RESULTS:
      Fixation in the dark along the midline remained as before, with vestibular jerk
      nystagmus continuously present. While saccades and pursuit to a visual target
      also remained the same as found earlier, fixation was somewhat worse, revealing
      not only saccadic intrusions but also a prominent right-jerk nystagmus.
      DISCUSSION: The results suggest lack of additional oculomotor neural plasticity
      after the end of the initial 10-year test period, and furthermore reveal apparent
      subtle age-related changes in oculomotor responsivity.

PMID- 12516799
TI  - Pseudotumor cerebri in a pre-pubescent child--case report.
AB  - BACKGROUND: Pseudotumor cerebri (PT) is a disease characterized by elevated
      intracranial pressure with no apparent etiology. A majority of cases of PTC occur
      in adults, with a distinct predilection for obese women of childbearing age. On
      rare occasions, PTC will affect children and is associated with different patient
      characteristics. CASE REPORT: A slender 10-year-old boy was brought to clinic
      with a one-day history of intermittent horizontal diplopia and a two-week history
      of severe headaches on awakening. Visual acuity, pupil function, and color vision
      were all normal. Cover test revealed an intermittent esotropia at distance, with
      full ocular motilities. Fundus examination revealed swelling of the optic disks
      OU. Further diagnostic testing, treatment, and followup are discussed.
      CONCLUSIONS: Pseudotumor cerebri in children is rare. When present, PTC in
      children often manifests different characteristics than adults. First, no clear
      sexual predilection exists for PTC in children. Second, the role of associated
      illnesses and medications is stronger in children than in adults. Third, the
      extent of neurologic deficit present in children with PTC is broader than in
      adults. All children with swollen optic disks warrant a thorough diagnostic
      evaluation. In the absence of obvious neuropathology, knowledge of the
      differences between adult and pediatric PTC can help avoid a diagnostic dilemma.

PMID- 12516800
TI  - Diagnosing glaucoma in pediatric aphakia.
AB  - BACKGROUND: Cataracts pose a serious threat to the visual system in infants and
      children, requiring prompt surgical intervention and rehabilitation to optimize
      visual development. Glaucoma is a serious complication following cataract surgery
      in infants and can lead to loss of vision. Early diagnosis of glaucoma, however,
      can be quite challenging in these patients. CASE REPORTS: Three cases are
      presented in which comeal edema was the initial presenting sign that led to the
      diagnosis of glaucoma during routine contact lens follow-up examinations for
      pediatric aphakia. CONCLUSION: The contact lens practitioner, during the course
      of management of aphakic infants and children, should always be suspicious of
      glaucoma as a complication of cataract surgery, and the presenting sign may be
      corneal edema.

PMID- 12516801
TI  - An outline for HIPAA compliance. Health Insurance Portability and Accountability
      Act.

PMID- 12516802
TI  - Expanded patient history.

PMID- 12516803
TI  - Human cytokine levels in nonperforated versus perforated appendicitis: molecular
      serum markers for extent of disease?
AB  - Appendicitis is a common surgical problem that is associated with a systemic
      inflammatory response. Previous studies have shown that cytokines are activated
      early in acute inflammation and sepsis and may serve as indicators of clinical
      severity. In this study we examined the role of cytokines as serum markers to
      distinguish nonperforated versus perforated appendicitis. Patients with the
      presumptive diagnosis of appendicitis had serum drawn preoperatively. Only
      patients (n = 59) with an intraoperative diagnosis of nonperforated (n = 34) and
      perforated (n = 25) appendicitis had serum drawn 12 hours postoperatively.
      Diagnosis was later confirmed by pathologic examination. The serum specimens were
      batch analyzed using enzyme-linked immunosorbent assays specific for interleukin
      (IL)-1beta, IL-2, IL-6, IL-8, and IL-10. Serum from normal healthy subjects
      served as control specimens (n = 9). Patients in the nonperforated and perforated
      groups were similar with regard to age, gender, race, white blood cell count, and
      fever. All cytokine levels including preoperative, postoperative, nonperforated,
      and perforated were higher in patients with appendicitis as compared with
      controls. IL-1beta, IL-2, and IL-10 levels were not different between groups with
      appendicitis. Preoperative serum levels of IL-6 (P = 0.036) and IL-8 (P = 0.047)
      were higher in patients with perforated versus nonperforated appendicitis. In
      addition postoperative serum levels of IL-6 (P = 0.0001) remained higher in the
      perforated group versus the nonperforated group. Serum levels of IL-6 and IL-8
      may have a role in discerning the extent of disease in this condition. This
      initial step in systemically studying the role of cytokines in this disease may
      ultimately lead to the development of molecular indicators to aid in diagnosis
      and differentiate appendicitis from other conditions.

PMID- 12516804
TI  - Histologic evaluation and treatment outcome after sequential radiofrequency
      ablation and hepatic resection for primary and metastatic tumors.
AB  - Operative manipulation during hepatic resection (HR) causes tumor cell shedding
      which is a factor in disease recurrence. Radiofrequency ablation (RFA) causes
      coagulative necrosis and was used to destroy the tumor before HR. We evaluated
      tumor necrosis and recurrence of hepatic malignancies treated by sequential
      RFA/HR. A retrospective review of patients treated with sequential RFA/HR from
      April 1999 to January 2002 was performed. A Radionics 500-kW RF generator was
      used to ablate lesions via H2O-cooled electrodes under ultrasound guidance.
      Segmental HR was performed after RFA. Resected specimens were reviewed with
      hematoxylin and eosin staining and for apoptosis. Patient follow-up ranged from
      10 to 33 months with evaluation of salient clinical, radiologic, and laboratory
      parameters. Seven patients (four male and three female) ages 62.1 +/- 10.3 years
      had sequential RFA/HR. Four patients had hepatocellular carcinoma (HCC) and three
      had colorectal metastases (CRm). The tumors were unifocal right-lobe lesions
      measuring 4.1 +/- 0.9 cm with a resection margin of 0.4 to 2.5 cm. Extensive
      necrosis was noted but intact nests of tumor cells occurred in all specimens with
      minimal apoptosis. Three of seven patients (two HCC and one CRm) developed
      pulmonary metastases at 3 to 20 months with one HCC patient developing concurrent
      liver metastases. Two deaths occurred in the HCC group. Sequential RFA/HR may
      minimize local recurrence; however, the high incidence of pulmonary metastases
      raises concern of transvenous migration. The histologic findings demonstrate foci
      of intact tumor cells after RFA. Controlled study of additional patients with
      long-term follow-up is necessary to better understand these findings.

PMID- 12516805
TI  - Acute diverticulitis in the young adult is not "virulent.".
AB  - Acute diverticulitis historically has been considered rare before the age of 40
      but "virulent" when it does occur and frequently requiring emergency operation.
      Recent experience suggests that the demographics and management of this disease
      are changing. Outcomes at Kaiser Permanente Los Angeles Medical Center were
      reviewed. Between January 1997 and July 2001 261 patients were discharged with
      the diagnosis of acute diverticulitis; 46 or 18 per cent of these were aged < or
      = 40. Patients' mean age was 35, 76 per cent were men, 65 per cent were Latino,
      and 72 per cent were obese (body mass index > or = 30 kg/m2). An operation at
      initial presentation was performed on 35 per cent (16/46) patients. Only 19 per
      cent of these (3/16) had a correct preoperative diagnosis. The 30 patients who
      were treated nonoperatively all were managed successfully; one required a
      percutaneous drain. Given the apparent increasing frequency of acute
      diverticulitis in young adults and the high success rate of initial nonoperative
      management surgeons should consider this diagnosis in selected patients who
      present with abdominal symptoms. Knowledge of typical clinical features and
      judicious use of computed tomography may decrease the number of unnecessary
      emergency operations in young adults with acute diverticulitis. Our data do not
      support a "virulent" label for this disease in the young.

PMID- 12516806
TI  - Day for night: should we staff a trauma center like a nightclub?
AB  - Most trauma services throughout the country are staffed on a fixed-call
      rotational basis. Staff is deployed in a linear fashion when trauma often occurs
      in a skewed sporadic fashion resulting in large fluctuations in volume, injury
      severity, and mechanism of injury. Medical error and increased mortality have
      been associated with certain admission times. We reviewed 8015 consecutive major
      trauma admissions over a 3-year period. When reviewing aggregate data we found a
      significant difference in mortality between patients admitted during the day
      (7:00 AM to 6:59 PM) compared with those admitted at night (7:00 PM to 6:59 AM)
      (10.1% vs 13.1%, P < 0.01). On further analysis the two populations were found to
      be significantly different in volume, Injury Severity Score (ISS), and mechanism
      of injury. More patients were admitted at night and on weekends. They had a
      higher ISS, higher frequency of penetrating trauma, and a higher likelihood of
      undergoing operative intervention. Multiple subset analyses were performed
      stratifying for ISS, time of admission, day of admission, and mechanism of injury
      using mortality rate as the end point. Six comparisons were performed: 1) morning
      versus night admission; 2) weekday versus weekend admission; 3) least busy day
      (Tuesday) versus busiest day (Sunday) admission; 4) weeknight versus weekend
      night admission; 5) in cases of penetrating trauma, morning versus night
      admission; and 6) in cases of blunt trauma, morning versus night admission. None
      of the six comparisons showed a significant difference in mortality. There was no
      significant difference in ISS-matched mortality related to fixed trauma call
      staffing.

PMID- 12516807
TI  - Does gallbladder ejection fraction predict pathology after elective
      cholecystectomy for symptomatic cholelithiasis?
AB  - Patients with symptomatic cholelithiasis are selected for elective
      cholecystectomy with the expectation that their symptoms will improve after
      operation. However, some patients fail to improve because their preoperative
      symptoms were not related to gallbladder disease. A test that would indicate the
      severity of gallbladder disease in patients with gallstones would therefore have
      great potential benefit. Twenty-five patients who presented as outpatients with
      episodic abdominal pain and gallstones were scheduled for elective
      cholecystectomy. On the day before operation patients underwent nuclear medicine
      cholescintigraphy with measurement of ejection fraction. All patients then
      underwent laparoscopic cholecystectomy. Pathologic specimens were reviewed by a
      pathologist who was blinded to the ejection fraction results and scored for
      degree of inflammation on a scale of zero to three. There was a wide range of
      ejection fractions measured (0-84%). There was, however, no correlation between
      ejection fractions and degree of gallbladder inflammation. We conclude that
      gallbladder ejection fraction does not predict the degree of gallbladder
      inflammation at the time of elective cholecystectomy. This test is therefore
      unlikely to predict which patients with cholelithiasis will have symptomatic
      relief after cholecystectomy.

PMID- 12516808
TI  - Wireless clinical alerts and patient outcomes in the surgical intensive care
      unit.
AB  - Errors in medicine have gained public interest since the Institute of Medicine
      published its 1999 report on this subject. Although errors of commission are
      frequently cited, errors of omission can be equally serious. A computerized
      surgical intensive care unit (SICU) information system when coupled to an event
      driven alerting engine has the potential to reduce errors of omission for
      critical intensive care unit events. Automated alerts and patient outcomes were
      prospectively collected for all patients admitted to a tertiary-care SICU for a 2
      year period. During the study period 3,973 patients were admitted to the SICU and
      received 13,608 days of care. A total of 15,066 alert pages were sent including
      alerts for physiologic condition (6,163), laboratory data (4,951), blood gas
      (3,774), drug allergy (130), and toxic drug levels (48). Admission Simplified
      Acute Physiology Score and Acute Physiology and Chronic Health Evaluation II
      score, SICU lengths of stay, and overall mortality rates were significantly
      higher in patients who triggered the alerting system. Patients triggering the
      alert paging system were 49.4 times more likely to die in the SICU compared with
      patients who did not generate an alert. Even after transfer to floor care the
      patients who triggered the alerting system were 5.7 times more likely to die in
      the hospital. An alert page identifies patients who will stay in the SICU longer
      and have a significantly higher chance of death compared with patients who do not
      trigger the alerting system.

PMID- 12516809
TI  - Management of gastrojejunal anastomotic leaks after Roux-en-Y gastric bypass.
AB  - Anastomotic leaks after Roux-en-Y gastric bypass (RYGB) potentially result in
      considerable morbidity and mortality. In the present report we describe our
      experience with the management of gastrojejunal anastomotic leaks. Tachycardia
      and fever are considered early signs of anastomotic disruption. Patients weighing
      less than 350 pounds underwent radiographic testing to diagnose gastrojejunal
      disruption. Those with severe leaks or patients too large for radiographic
      evaluation underwent exploratory laparotomy. For severe anastomotic disruptions a
      retrograde transanastomotic jejunal sump drain was placed. Twenty-four (1.3%)
      anastomotic leaks occurred in 1789 RYGBs. Five of the leaks were classified as
      severe and required retrograde sump tube placement. There was one mortality and
      all of the other patients completely recovered. Aggressive and early intervention
      for anastomotic disruption after RYGB is necessary to ensure the best possible
      outcomes for patients with this complication. A high index of suspicion for leaks
      in postoperative RYGB patients with tachycardia is required if patients are to
      have good outcomes when complications develop.

PMID- 12516810
TI  - Decompressive craniectomy in trauma patients with severe brain injury.
AB  - Decompressive craniectomy in the treatment of severe traumatic brain injury (TBI)
      is controversial. We conducted a retrospective review of prospectively collected
      data on all patients requiring surgery for TBI from 1995 through 2001 at Cedars
      Sinai Medical Center. Patients were separated into two groups: Group A,
      craniectomy, and Group B, craniotomy. We had 120 patients; 24 (20%) had
      craniectomy and 96 (80%) had craniotomy. There were no significant differences in
      demographics or Injury Severity Scores. The craniectomy group had significantly
      more TBI as evidenced by more frequently collapsed basilar cisterns on CT scan (P
      = 0.0001). There was no significant difference in actuarial survival between the
      groups: 52.8 per cent in the craniectomy group and 79.2 per cent in the
      craniotomy group (P = 0.08). Calculated mortality for craniectomy was 37.5 per
      cent versus 18.8 per cent for craniotomy (P = NS). We found four preoperative
      findings to be significant predictors of mortality: 1) Glasgow Coma Scale score,
      2) Injury Severity Score, 3) Simplified Acute Physiology Score, and 4) Acute
      Physiology and Chronic Health Evaluation II. The type of surgery was not found to
      be a significant predictor of death even when adjusted for severity of injury.
      Craniectomy may be helpful for patients with TBI associated with preoperative CT
      scan evidence of basilar cistern collapse. This is evidenced by similar survival
      rates between the two groups despite clinical evidence of greater TBI among
      craniectomy patients.

PMID- 12516811
TI  - Oral antibiotics in the management of perforated appendicitis in children.
AB  - After appendectomy for perforated appendicitis children have traditionally been
      managed with intravenous broad-spectrum antibiotics for 5 to 10 days and then
      until fever and leukocytosis have resolved. We prospectively evaluated a protocol
      of hospital discharge on oral antibiotics when oral intake is tolerated
      regardless of fever or leukocytosis-in a consecutive series of 80 children
      between one and 15 years of age who underwent appendectomy (38 open and 42
      laparoscopic) for perforated appendicitis. At discharge subjects began a 7-day
      course of oral trimethoprim/sulfamethoxazole and metronidazole. Patients were
      discharged between 2 and 18 days postoperatively (mean 5.3 days). Sixty-six were
      discharged on oral antibiotics, and 28 of these had persistent fever or
      leukocytosis. Two patients (2.5%) developed postoperative intra-abdominal
      abscesses while inpatients. Wound infections developed in seven patients (8.8%)
      four of whom were on intravenous antibiotics. Among the 66 children who were
      discharged on oral antibiotics without having had an inpatient infectious
      complication there were three wound infections (4.4%). None of these patients had
      a fever or leukocytosis at discharge. We conclude that after appendectomy for
      perforated appendicitis children may be safely discharged home on oral
      antibiotics when enteral intake is tolerated regardless of fever or leukocytosis.

PMID- 12516812
TI  - Repair of recurrent pectus deformities.
AB  - A paucity of information is available regarding the surgical repair of recurrent
      pectus deformities (RPD). From 1993 through 2001 35 patients ranging in age from
      6 to 51 years (mean, 23 years) underwent repair of RPD a mean of 11 years after
      the original repair: modified Ravitch repair (31), prosthetic implantation
      (three), and Nuss procedure (one). All patients had accompanying symptoms
      including decreased stamina (76%), chest discomfort (53%), asthma (33%). The
      repair performed was dependent on the findings at operation. A modified Ravitch
      procedure with Adkins strut was performed for 21 patients. Three had reattachment
      of mobile costal cartilages and/or xiphoid process to the sternum; three patients
      had autologous bone or cartilage grafts, three had muscular reconstruction, and
      two had resection of a localized cartilage protrusion. Three patients could not
      be reconstructed safely. Very good to excellent results were achieved for 32
      patients (mean follow-up, 24.8 months). There were no deaths or major
      complications. Minor complications occurred in five patients. The mean blood loss
      was 105 mL. The mean hospital stay was 2.8 days. We conclude that although it is
      technically difficult RPD can be repaired with low morbidity, short hospital
      stay, and very good physiologic and cosmetic results.

PMID- 12516813
TI  - Are preoperative serum calcium, parathyroid hormone, and adenoma weight
      predictive of postoperative hypocalcemia?
AB  - The objective of this study is to determine whether preoperative serum calcium,
      parathyroid hormone, or adenoma weight is predictive of postoperative
      hypocalcemia after removal of a parathyroid adenoma. A retrospective chart review
      was performed for consecutive parathyroidectomy patients over a 6-year period at
      a community-based teaching institution. Patients with renal failure (serum
      creatinine >1.7), hyperplastic disease, and parathyroid carcinoma were excluded.
      The outcome measures were postoperative serum calcium and the presence of signs
      or symptoms such as paresthesias, anxiety, or Chvostek's sign. One hundred forty
      one patients underwent parathyroidectomy during the study period. Fifty-four
      patients were excluded as a result of hyperplastic disease, renal failure,
      carcinoma, or unavailable records. Of the remaining 87 patients 25 (28.7%)
      developed hypocalcemia (serum calcium < 8.0), and ten patients (11.5%), developed
      symptoms. The mean preoperative calcium levels for the normocalcemic and
      hypocalcemic groups were 10.9 and 10.6, respectively (P < 0.217). The mean
      preoperative parathyroid hormone levels (normal 10-54) were 214 and 139,
      respectively (P < 0.305), and the mean adenoma weights were 1.059 and 1.337 g
      respectively (P < 0.343). This study demonstrates no statistically significant
      difference in the mean preoperative serum calcium levels, parathyroid hormone
      levels, or adenoma weight between normocalcemic and hypocalcemic patients
      postoperatively.

PMID- 12516814
TI  - Immediate preoperative injection of 99m-Tc sulfur colloid is effective in the
      detection of breast sentinel lymph nodes.
AB  - Sentinel lymph node (SLN) biopsy is an accurate technique to determine the
      metastatic status of lymph nodes. Radionuclide guidance makes the procedure
      easier and improves the success rate. Coordinating the operating room and nuclear
      medicine schedules causes delays when same-day radionuclide injection is used. We
      hypothesized that injection of 99m-Tc sulfur colloid immediately preoperatively
      is effective in SLN detection. We analyzed a prospective database of 70 patients
      treated at Harbor-UCLA Medical Center. The first 39 patients underwent completion
      axillary dissection (Group A) and subdermal injection of sulfur colloid
      immediately before surgery. A second group of 31 patients (Group B) had
      intraparenchymal injection immediately before surgery. We used isosulfan blue in
      all cases. SLNs were identified in 97 per cent of cases. SLNs were radioactive in
      94 per cent and blue in 90 per cent. In Group A the accuracy and the positive and
      negative predictive values of SLN biopsy were 100 per cent. SLN counts per second
      ranged from 22 to 1700. The mean count per second was 290 +/- 281 (mean +/-
      standard deviation). Subdermal and intraparenchymal injections were equally
      successful (93% vs 92%). In conclusion injection of radiocolloid and isosulfan
      blue immediately preoperatively is highly successful and accurate in the
      detection of SLNs in breast cancer. It avoids operating room schedule delays.

PMID- 12516815
TI  - Technical consideration in the management of chronic mesenteric ischemia.
AB  - Our aging population may result in a rise in the prevalence of chronic mesenteric
      ischemia. This report reviews our contemporary experience with a tailored
      surgical approach to chronic mesenteric ischemia. The medical records of 17
      patients operated on for chronic mesenteric ischemia were retrospectively
      reviewed. Symptom-free survival and long-term patency documented by duplex
      scanning when available were also analyzed. Sixteen patients ranging in age from
      32 to 80 years were included in the study. Seventy-five per cent of the patients
      were female. The most common preoperative complaints were postprandial abdominal
      pain and weight loss. Revascularization was tailored to the arterial anatomy and
      included bypass to the superior mesenteric artery (SMA) alone (eight), bypass to
      the celiac artery and SMA (six), SMA reimplantation onto the aorta (one),
      SMA/inferior mesenteric artery reimplantation (one), and transaortic
      endarterectomy of the celiac artery/SMA (one). Bypass conduits included Dacron
      (eight), saphenous vein (four), and polytetrafluoroethylene (two). Bypass grafts
      originated from the supraceliac aorta in 12 patients; the remaining bypass
      originated from the left limb of an aortofemoral graft. There was one
      perioperative death (mortality 5.6%). Follow-up duplex scans at a mean of 34
      months (range 1-114) showed no graft thromboses. We conclude that a variety of
      surgical techniques can provide durable relief of mesenteric ischemia. A tailored
      approach to revascularization optimizes patency and provides long-term symptom
      free survival.

PMID- 12516816
TI  - The effect of cisapride on the success of early feeding after elective open colon
      resection.
AB  - Early postoperative feeding after open colon resection has been shown to be safe
      and effective. However, approximately 13 per cent of patients fail to tolerate
      it. We hypothesized that the use of promotility agents may decrease failure of
      early postoperative feeding after elective open colectomy. As part of a
      consecutive case series metoclopramide or cisapride was administered to patients
      undergoing open colectomy as part of an early feeding protocol. The early feeding
      protocol consisted of instituting a clear liquid diet on postoperative day (POD)
      2, followed by a regular diet on POD 3. One hundred fifty-one patients received
      early-feeding without promotility agents (Group I). The next 49 patients were
      treated with metoclopramide (Group II), and 31 patients received cisapride (Group
      III). In Group I 20 of 151 patients (13.2%) failed early feeding, and the mean
      hospital stay was 3.77 days (range 3-11 days). In Group II seven of 49 patients
      (14.2%) failed early postoperative feeding, and the mean hospital stay was 3.67
      days (range 3-8 days). Group III had no patients who failed to tolerate early
      feeding, and the mean hospital stay was 3.32 days (range 3-5 days). There were no
      anastomotic leaks or abdominal abscesses in any group. No cardiac arrhythmias
      were associated with cisapride. A decrease in early feeding failure was observed
      with cisapride, administration.

PMID- 12516817
TI  - Nonoperative management of blunt renal trauma: a prospective study.
AB  - Despite the abundance of literature on nonoperative management (NOM) of blunt
      trauma to the liver and spleen there is limited information on NOM of blunt renal
      injuries. In an effort to evaluate the role of NOM 37 consecutive unselected
      patients with renal injuries (grade 1, four; grade 2, 12; grade 3, 11; grade 4,
      six; and grade 5, four) were followed prospectively over 30 months (Match 1999 to
      September 2001). Patients without peritonitis or hemodynamic instability were
      managed nonoperatively regardless of the appearance of the kidney on CT scan. Six
      (16%) patients were operated on immediately but only two (5.4%) for the kidney
      (grades 3 and 5 respectively). Of the remaining 31 patients 26 (84%) were managed
      successfully without an operation (grade 1 or 2, 12; grades 3-5, 14). Five
      patients were taken to the operating room after a period of observation (3, 3.5,
      9, 36, and 44 hours respectively) but only three for the kidney (grades 4 and 5).
      The overall failure rate was 16 per cent (5 of 31); the rate of failure
      specifically related to the renal injury was 9.6 per cent (three of 31). Compared
      with the patients with successful NOM the five patients with failed NOM were more
      severely injured (Injury Severity Score > or = 15 in 80% vs 27%, P = 0.04),
      required in the first 6 hours more fluids (4.17 +/- 1.72 vs 1.87 +/- 1.4 liters,
      P = 0.003) and blood transfusions (2.40 +/- 2 vs 0.42 +/- 1.17 units, P = 0.005),
      and more frequently had a positive trauma ultrasound (80% vs 11.5%, P = 0.005).
      We conclude that NOM is the prevailing method of treatment after blunt renal
      trauma. It is successful in the majority of patients without peritonitis or
      hemodynamic instability and should be considered regardless of the severity of
      renal injury. Predictors of failure may exist on the basis of injury severity,
      fluid and blood requirements, and abdominal ultrasonographic findings and need
      validation by a larger sample size.

PMID- 12516818
TI  - Complications of hemodialysis access in HIV-positive patients.
AB  - As long-term arteriovenous (AV) access for hemodialysis becomes more prevalent in
      human immunodeficiency virus (HIV)-positive patients it is important to evaluate
      the complications associated with each surgical technique. The records of 37
      consecutive HIV-positive patients undergoing surgery for AV hemodialysis access
      were reviewed. Cases were analyzed for age, gender, presence of acquired
      immunodeficiency syndrome (AIDS), surgical procedure, and complications. AV
      fistulas were performed primarily in 23 patients, and prosthetic grafts were used
      in 14. There was no difference between these two groups in regard to age (P =
      0.510), gender (P = 0.620), or presence of AIDS (P = 0.97). Complications
      requiring one or more reoperations occurred in four patients (17%) after AV
      fistulas and in seven patients (50%) after AV grafts (P = 0.035). When
      reoperations were accounted for a total of 28 AV fistulas and 20 AV grafts were
      performed with an overall complication rate of 21 and 70 per cent respectively (P
      = 0.001). Complications after AV grafts included thrombosis (40%), infection
      (25%), and aneurysm (5%). Thrombosis was the only complication observed after AV
      fistula (21%). The complication rate after AV access in HIV-positive patients was
      significantly greater after AV graft insertion than after AV fistulas, which
      resulted in a higher rate of reoperation. AV fistula when feasible should be
      considered the procedure of choice in this group of patients.

PMID- 12516819
TI  - Is duplex ultrasonography an effective single modality for the preoperative
      evaluation of peripheral vascular disease?
AB  - The purpose of this study was to determine whether duplex ultrasonography can be
      used as an effective modality for the preoperative evaluation of lower-extremity
      arterial occlusive disease. The records of all patients undergoing both color
      flow duplex scanning and contrast arteriography of the lower extremities during a
      13-month period were reviewed. Comparisons between the two modalities were made
      at the femoral, popliteal, and tibial artery levels. Sensitivity, specificity,
      positive predictive value, negative predictive value, and overall accuracy were
      calculated for duplex scanning using angiography as the gold standard. Three
      hundred fifteen arterial segments were evaluated. Color flow imaging
      overestimated the degree of stenosis in seven vessels and underestimated the
      degree of stenosis in four vessels. Overall duplex ultrasonography accurately
      determined lower-extremity arterial anatomy as defined by contrast arteriography
      with a sensitivity of 96.9 per cent, a specificity of 96.2 per cent, a positive
      predictive value of 94.6 per cent, a negative predictive value of 97.8 per cent,
      and an overall accuracy of 96 per cent. The accuracy of duplex ultrasonography
      must be determined in each individual vascular laboratory. Once this is
      satisfactorily accomplished color flow scanning may be used as the single imaging
      modality for lower-extremity arterial occlusive disease in selected patients
      deemed to be at high risk for contrast angiography.

PMID- 12516820
TI  - Intensive care unit outcome of vehicle-related injury in elderly trauma patients.
AB  - Vehicle-related trauma is a common mechanism of injury in elderly (age > or = 65
      years) trauma patients. Several hospital-based studies have shown that patients
      with pedestrian injury have a higher mortality compared with those with motor
      vehicle collision (MVC) injury partially because of older patients found in the
      former group. In addition the injury patterns also differ significantly between
      these two mechanisms of vehicle-related trauma. The purpose of the present study
      is to compare the demographics, injury severity, injury patterns, and outcomes of
      elderly patients with pedestrian injury admitted to a surgical intensive care
      unit (SICU) of a Level I trauma center between January 1, 1994 and December 31,
      2000 with those admitted with MVC injury. During the study period there were 187
      elderly patients admitted to the surgical intensive care unit with vehicle
      related injury. Fifty-one per cent of the patients had MVC injury. Patients were
      divided into two groups based on their mechanisms of injury (pedestrian vs MVC)
      for comparison. There was no difference in the mean age and gender between the
      two groups. Injury Severity Score, admission Simplified Acute Physiology Score,
      and mortality were significantly higher in the pedestrian group compared with the
      MVC group. Using logistic regression analysis three factors were found to be
      independently predictive of mortality: Simplified Acute Physiology Score,
      intracranial hemorrhage with mass effect on CT scan, and cardiac complications.

PMID- 12516821
TI  - Superior long-term results of renal transplantation in children under 5 years of
      age.
AB  - Despite improving overall results of pediatric renal transplantation children
      under 5 years of age remain a high-risk group with poorer outcomes often because
      of a higher rate of surgical complications. This retrospective report details a
      12-year experience at a single center and examines the outcome in this high-risk
      group of patients. We reviewed the medical records of 21 children under 5 years
      of age who received renal transplantation at Loma Linda University Medical Center
      between July 1988 and August 2000. The patients were evaluated regularly by the
      same pediatric nephrologist throughout the study period at our outpatient clinic.
      Mean recipient age was 3 +/- 1.2 (range 2-5) years; weight at transplantation was
      13.3 +/- 5.4 kg. Ten (48%) patients received living related donor (LRD) kidneys
      and 11 (52%) received cadaver (CAD) kidneys. Mean donor ages for CAD and LRD were
      14.4 +/- 10 years and 26.6 +/- 4.9 years, respectively. The mean cold ischemia
      time (CAD only) was 23.3 +/- 10.6 hours. Renal dysplasia (n = 8) and obstructive
      uropathy (n = 5) were the most common primary diagnoses. Maintenance
      immunosuppression consisted of Azathioprine or mycophenolate mofetil (MMF),
      cyclosporine or tacrolimus and prednisone. Mean follow-up was 80.1 +/- 51.4
      months. Twelve (57%) grafts have a follow-up >5 years. Patient survival was 100
      per cent. Overall graft survival at one, 3, 5, and 10 years were 95, 95, 88, and
      88 per cent respectively. Graft survival for LRD recipients was 100 per cent. No
      graft was lost as a result of a technical problem or vascular thrombosis. One
      graft each was lost because of delayed graft function complicated by severe
      cytomegalovirus infection and chronic rejection. At one year the mean serum
      creatinine was 0.6 +/- 0.2 mg/dL with a mean calculated glomerular filtration
      rate of 93 +/- 32 mL/min. All 17 children who are now of school age are attending
      school. We conclude that excellent rehabilitation and superior long-term patient
      and graft survival can be achieved with renal transplantation in children of this
      age group with the use of good surgical techniques and close follow-up.

PMID- 12516822
TI  - Carotid endarterectomy using regional anesthesia: a benchmark for stenting.
AB  - Regional block (RB) anesthesia for carotid surgery offers the advantage of
      continuously monitoring the awake patient's neurologic status during carotid
      cross-clamping. We retrospectively studied our experience with RB for carotid
      endarterectomy (CEA) procedures performed during the period January 1, 1995
      through December 31, 2001. A total of 388 consecutive CEA procedures were
      performed; RB was used in 314 and general anesthesia (GA) in 74. Three patients
      required conversion from RB to GA. GA was used only in patients who could not
      tolerate a block or needed combined coronary artery bypass grafting (CABG) and
      carotid surgery. New ipsilateral stroke did not occur in RB patients; one patient
      extended a previous stroke. Three in-hospital deaths occurred; these were all
      cardiac-related. In GA patients undergoing CEA without CABG (CEA only, n = 58),
      one stroke and no deaths occurred. The combined stroke and mortality rate for all
      CEA-only patients was 1.3 per cent (five of 372). RB allows 90 per cent of
      procedures to be performed without shunting, thus facilitating endarterectomy and
      patch angioplasty. CEA performed under RB is similar to carotid stenting because
      both procedures allow monitoring of the awake patient's neurologic status. The
      very low procedural complication rate in this study warrants the consideration of
      carotid surgery under regional block as a benchmark for future carotid
      angioplasty and stenting studies.

PMID- 12516823
TI  - Commitment.

PMID- 12516824
TI  - Clinical experience with In-Ceram Spinell crowns: 5-year follow-up.
AB  - Prompted by increased patient requests for esthetic treatment, restorative
      clinicians have evaluated a variety of new materials and procedures. This study
      reports on 5 years' experience with In-Ceram Spinell all-ceramic crowns. A total
      of 40 anterior crowns were positioned in 13 patients from October 1995 to
      December 1998. The clinical examination was made following modified California
      Dental Association/Ryge criteria. Final evaluation was carried out in October
      2000, for an observation period of 22 to 60 months (mean 50 months). Only one
      failure was recorded, and the fractured crown needed to be replaced; according to
      Kaplan-Meier analysis, the estimated success rate was 97.5%. A thorough
      description of the clinical procedures through which anterior teeth can be
      successfully treated with all-ceramic Spinell crowns is described.

PMID- 12516825
TI  - Bone-implant contact and bone quality: evaluation of expected and actual bone
      contact on machined and osseotite implant surfaces.
AB  - This article introduces a new technique using histomorphometrics to estimate the
      extent of bone-to-implant contact that might be expected on an implant surface in
      relation to the quality of the surrounding bone. Two implant surfaces, one
      machined and one Osseotite, were compared on the same implant in the same patient
      Eleven of these custom-made 2-mm-diameter implants were placed in the posterior
      maxilla and allowed to integrate. After 6 months of nonloaded healing, implants
      were trephined with surrounding bone tissue and prepared into histologic
      sections. Digitized images were analyzed at 50x magnification with image-analysis
      software. Bone surface area was calculated over the entire microscopic field, and
      the actual bone-to-implant contact for each implant surface was measured. The
      expected bone-to-implant contact was calculated by superimposing the profile of
      the implant threads on the bone image a small increment (0.15, 0.5, or 1.0 mm)
      from the actual implant site and counting the linear amount of bone that would be
      in contact with the implant surface. The actual bone-to-implant contact for
      Osseotite was greater than its expected bone-to-implant contact, whereas the
      actual bone-to-implant contact for the machined surface was mostly lower than the
      expected values. Thus, the Osseotite surface appears to exert a positive effect
      on the amount of bone approaching the implant surface and can be described as
      conductive, while the machined surface is nonconductive. This technique may serve
      to predict the clinical success that the Osseotite surface will demonstrate in
      poor-quality bone.

PMID- 12516826
TI  - Technique for producing platelet-rich plasma and platelet concentrate: background
      and process.
AB  - Autologous platelet-rich plasma is a source of platelet-derived growth factor
      (PDGF) and transforming growth factor beta (TGF-beta), both important in
      accelerating hard and soft tissue maturation. This article describes a two-step
      centrifugation method to sequester and concentrate platelets to a level four to
      eight times baseline whole blood values. The technique produces concentrations of
      PDGF-AB above 500% and TGF-beta1 greater than 800%. Flow cytometry measuring p
      selectin expression shows that the platelets remain quiescent throughout the
      procedure, maintaining their integrity and viability, with no inadvertent
      activation.

PMID- 12516827
TI  - Connective tissue-bone onlay graft with enamel matrix derivative for treatment of
      gingival recession: a case report.
AB  - We describe a case of gingival recession in which root coverage and coronal bone
      regrowth were achieved after treatment with a connective tissue-bone graft and
      enamel matrix derivative. The connective tissue-bone graft was harvested from a
      maxillary edentulous area and then curved to fit the root surfaces of the
      maxillary left central and lateral incisors. Enamel matrix derivative was applied
      to the root surfaces, and the connective tissue-bone graft was fixed to the
      interdental bone by a titanium screw. Six months later, the exposed roots were
      covered with thick gingiva, and coronal regrowth of thick bone was evident at
      reentry surgery. This technique is useful for esthetic restoration placement with
      an intracrevicular margin on teeth with a thin, receding gingiva.

PMID- 12516828
TI  - A clinical and histologic evaluation of a block onlay graft in conjunction with
      autogenous particulate and inorganic bovine mineral (Bio-Oss): a case report.
AB  - This article describes a clinical case report in which an autogenous intraorally
      harvested block graft was used in combination with particulate autogenous and
      inorganic bovine mineral for localized alveolar ridge augmentation. No barrier
      was used above the graft material. Clinical evaluation revealed excellent
      integration of the graft material to the recipient site, while histologic
      analysis indicated that the block graft was vital and undergoing an active
      remodeling process. Excellent integration of the inorganic bovine mineral with
      the newly formed bone was also observed, suggesting that this material can be
      used as a filler for onlay grafting procedures.

PMID- 12516829
TI  - A 6-year unloaded hydroxyapatite-coated dental implant placed into an extraction
      socket in conjunction with nonresorbable hydroxyapatite grafting material:
      histologic evaluation.
AB  - A submerged hydroxyapatite (HA)-coated implant placed into a fresh extraction
      socket in conjunction with a nonresorbable HA graft was harvested after 6 years
      of unloaded healing. The implant and surrounding bone were processed for
      histologic analysis. The HA coating appeared to be stable and homogenous. An
      excellent bone-to-implant contact could be found along the entire implant length.
      No signs of HA resorption or detachment were found. The HA graft was still
      recognizable histologically around the apical third of the implant. Light
      microscopy revealed a good osteoconductive ability of the HA particles, which did
      not show any signs of remodeling or resorption. These findings suggest that HA
      coated implants may be able to maintain optimal osseointegration over time, even
      in the absence of loading.

PMID- 12516830
TI  - Enamel matrix proteins (Emdogain) in combination with coronally advanced flap or
      subepithelial connective tissue graft in the treatment of shallow gingival
      recessions.
AB  - This article describes two different surgical techniques of root coverage using
      Emdogain and shows preliminary results on 26 shallow recessions in 14 patients.
      For the treatment of 13 recessions, Emdogain was used in combination with a
      coronally advanced flap (CAF+EMD group). In the other 13 recessions, Emdogain and
      the flap were used in combination with a subepithelial connective tissue graft
      (CAF+CTG+EMD group). For the CAF+EMD group, the root coverage at 6 months was
      93.97%, with an attachment gain of 3.2 mm; for the CAF+CTG+EMD group, the root
      coverage was 93.59%, with an attachment gain of 3.4 mm (no statistically
      significant difference between groups). When complete root coverage was not
      achieved, the residual recession was 1 mm in four cases and 2 mm in one case.
      Keratinized gingiva was increased for both groups, but more for the CAF+CTG+EMD
      group (1.38 mm versus 0.69 mm; statistically significant difference). Clinical
      attachment level decreased significantly in both groups, from 4.46 to 1.23 mm in
      the CAF+EMD group, and from 4.62 to 1.23 mm in the CAF+CTG+EMD group. Preliminary
      results show that Emdogain, in combination with CAF or CAF+CTG for the treatment
      of Miller Class I or II gingival recessions, displays good clinical results, with
      percentage of root coverage comparable or superior to other techniques. Further
      experimental studies on the dynamics of wound healing are needed to prove that
      EMD is really responsible for improving the percentage of regenerated versus
      repaired tissues with respect to other techniques.

PMID- 12516831
TI  - A comparative study of combined treatment with a collagen membrane and enamel
      matrix proteins for the regeneration of intraosseous defects.
AB  - Recent clinical study shows that periodontal regeneration therapy using enamel
      matrix proteins (Emdogain; EMD) is expected to have the same therapeutic effect
      as guided tissue regeneration (GTR). However, reports on the combined effect of
      both therapies are limited, and the clinical significance is not definite. In
      this study, clinical effects were studied by comparing a combination of EMD and
      GTR using a collagen membrane for intrabony defects with GTR monotherapy and EMD
      monotherapy. Sixty-one patients with 69 intrabony defects were included. Efficacy
      of treatment was evaluated at 6 months and 1 year by assessment of reduction of
      probing depth, probing attachment gain, and radiographic bone gain. There were no
      statistically significant differences between presurgical soft tissue
      measurements and defect characteristics for the three treatment groups. The
      results showed no significant differences in reduction of probing depth, probing
      attachment gain, or radiographic bone gain between the three treatment groups at
      both evaluation times. The combination of GTR using a resorbable membrane for
      intrabony defects and EMD did not enhance the therapeutic effect compared with
      each monotherapy.

PMID- 12516832
TI  - Rotated palatal flap. A surgical approach to increase keratinized tissue width in
      maxillary implant uncovering: technique and clinical evaluation.
AB  - Although keratinized mucosa is not indispensible for the maintenance of
      periimplant tissue health if oral hygiene is adequate, its presence is generally
      advocated. The establishment of an adequate zone of gingiva that is firmly
      attached to the underlying periosteum and bone is important for the overall long
      term success of implant-supported oral rehabilitation. The purpose of this study
      was to describe and evaluate a surgical approach for maxillary implant uncovering
      that augments the buccal periimplant keratinized tissue while avoiding a large
      zone of exposed implant-supporting bone by using a rotated palatal flap. The
      study comprised 40 implants that were uncovered in 13 patients using a
      combination of full-thickness buccally repositioned and rotated palatal flaps.
      Within each patient, the mean preoperative width of keratinized mucosa was 0.19
      mm (SD 0.316), and the mean postoperative width was 3.45 mm (SD 0.489). The
      difference between post- and preoperative widths was 3.26 mm (SD 0.498), which
      was statistically significant according to a paired t test (P < .0001). The main
      advantages of this technique are simplicity and predictability, and it
      consistently provides a wider zone of keratinized gingiva in the buccal aspect of
      the future maxillary implant-supported restoration.

PMID- 12516833
TI  - What does a 'right' to physician-assisted suicide (PAS) legally entail?
AB  - "What Does a Right to Physician-Assisted Suicide (PAS) Legally entail?" Much of
      the bioethics literature focuses on the morality of PAS but ignores the legal
      implications of the conclusions thereby wrought. Specifically, what does a legal
      right to PAS entail both on the part of the physician and the patient? I argue
      that we must begin by distinguishing a right to PAS qua "external" to a
      particular physician-patient relationship from a right to PAS qua "internal" to a
      particular physician-patient relationship. The former constitutes a negative
      claim right in rem that prohibits outside interference with the exercise of a
      right to PAS while the latter can provide the patient with a positive claim right
      in personam to obligatory assistance from his physician. Importantly, I argue
      that the creation of such a patient right, however, originates with the physician
      who may exercise an unqualified right of first refusal prior to promising to help
      her patient commit suicide. In doing so, I hope to establish that explicit
      physician promises of assistance in dying should become legally binding. As such,
      current PAS law in both The Netherlands and Oregon is in need of substantive
      modification.

PMID- 12516834
TI  - Should doctors suggest euthanasia to their patients? Reflections on Dutch
      perspectives.
AB  - During the summer of 1999 and in April 2002 I went to The Netherlands in order to
      meet some of the leading authorities on the euthanasia policy. They were asked
      multiple questions. This study reports the main findings to the question: should
      doctors suggest euthanasia to their patients? Some interviewees did not observe
      any significant ethical concerns involved in suggesting euthanasia. For various
      reasons they thought physicians should offer euthanasia as an option. Two
      interviewees asserted that doctors don't propose euthanasia to their patients.
      Five interviewees objected to physician's initiative.

PMID- 12516835
TI  - Life is more than a survey: understanding attitudes toward euthanasia in Japan.
AB  - Empirical studies in bioethics, as well as clinical experience, demonstrate the
      existence of inter- and intra-cultural diversity in values and perspectives on
      end-of-life issues. This paper argues that while survey research can describe
      such diversity, explaining it requires ethnographic methodology that allows
      ordinary people to frame the discussion in their own terms. This study of
      attitudes toward euthanasia in Japan found that people face conflicts between
      deeply held values such as life versus pain, self versus other, and burden versus
      self-reliance that make it difficult to rely on a "rational person" approach to
      decision-making. An inductive ethnographic approach grounded in people's life
      experiences can indicate the reasons for variation in responses to surveys, and
      can clarify the nature of ethical conflict in a particular cultural setting.

PMID- 12516836
TI  - Proportionality, terminal suffering and the restorative goals of medicine.
AB  - Recent years have witnessed a growing concern that terminally ill patients are
      needlessly suffering in the dying process. This has led to demands that
      physicians become more attentive in the assessment of suffering and that they
      treat their patients as 'whole persons.' For the most part, these demands have
      not fallen on deaf ears. It is now widely accepted that the relief of suffering
      is one of the fundamental goals of medicine. Without question this is a positive
      development. However, while the importance of treating suffering has generally
      been acknowledged, insufficient attention has been paid to the question of
      whether different types of terminal suffering require different responses from
      health care professionals. In this paper we introduce a distinction between two
      types of suffering likely to be present at the end of life, and we argue that
      physicians must distinguish between these types if they are to respond
      appropriately to the suffering of their terminally ill patients. After
      introducing this distinction and explaining its basis, we further argue that the
      distinction informs a (novel) principle of proportionality, one that should guide
      physicians in balancing their competing obligations in responding to terminal
      suffering. As we explain, this principle is justified by reference to the
      interests terminally ill patients have in restoration, as well as in the relief
      of suffering, at the end of life.

PMID- 12516837
TI  - Managed care's reconstruction of human existence: the triumph of technical
      reason.
AB  - To achieve its goals of managing and restricting access to psychiatric care,
      managed care organizations rely on an instrument, the outpatient treatment
      report, that carries significant implications about how they view psychiatric
      patients and psychiatric care. In addition to involving ethical transgressions
      such as violation of patient confidentiality, denial of access to care, spurious
      use of concepts like quality of care, and harassment of practitioners, the
      managed care approach also depends on an overly technical, instrumental
      interpretation of human beings and psychiatric treatment. It is this grounding of
      managed care in technical reason that I will explore in this study. I begin with
      a review of a typical outpatient treatment report and show how, with its
      dependence on the DSM-IV, on behavioral symptoms and patient 'functioning', on
      the biomedical model of psychiatric illness, and on gross quantitative measures,
      the report results in a crude, skeletonized view of the human being as a
      congeries of behavioral symptoms and functions. I then develop the managed care
      construal of human existence further by showing its grounding in technical
      reason, exploring the latter in its modern embodiment and deriving it and its
      opposite, practical reason, from Aristotle's distinction between technical and
      practical reason, techne and phronesis. In this analysis of the role of technical
      reason in managed care, I point out that managed care did not have to develop its
      rationale de novo but could rather lift its arguments, e.g. the biomedical model,
      from contemporary psychiatry and simply apply them in a restrictive manner.
      Finally, I conclude this study by arguing for psychiatry's status as a discipline
      of practical knowledge.

PMID- 12516838
TI  - The research subject as wage earner.
AB  - The practice of paying research subjects for participating in clinical trials has
      yet to receive an adequate moral analysis. Dickert and Grady argue for a wage
      payment model in which research subjects are paid an hourly wage based on that of
      unskilled laborers. If we accept this approach, what follows? Norms for just
      working conditions emerge from workplace legislation and political theory. All
      workers, including paid research subjects under Dickert and Grady's analysis,
      have a right to at least minimum wage, a standard work week, extra pay for
      overtime hours, a safe workplace, no fault compensation for work-related injury,
      and union organization. If we accept that paid research subjects are wage earners
      like any other, then the implications for changes to current practice are
      substantial.

PMID- 12516839
TI  - The ontological status of human DNA: is it not first and foremost a biological
      "file self"?
AB  - This paper investigates which of the various legal notions proposed for human DNA
      is the most appropriate from an ontological viewpoint - unique legal status,
      private property, common property, person, or information. The focus is on the
      difficulties that private property, common property and person present. By using
      Harre's notion of "file-self" we argue that, ontologically, the most appropriate
      legal notion to be applied is information. This has consequences for storage,
      control and use of genetic information as well as identifiable human body
      material.

PMID- 12516840
TI  - Medical evidence and virtue ethics: a commentary on Zarkovich and Upshur.

PMID- 12516841
TI  - The virtues of evidence.
AB  - Evidence-based medicine has been defined as the conscientious and judicious use
      of current best evidence in making clinical decisions. This paper will attempt to
      explicate the terms "conscientious" and "judicious" within the evidence-based
      medicine definition. It will be argued that "conscientious" and "judicious"
      represent virtue terms derived from virtue ethics and virtue epistemology. The
      identification of explicit virtue components in the definition and therefore
      conception of evidence-based medicine presents an important starting point in the
      connection between virtue theories and medicine itself. In addition, a
      unification of virtue theories and evidence-based medicine will illustrate the
      need for future research in order to combine the fields of virtue-based
      approaches and clinical practice.

PMID- 12516842
TI  - Anorectal physiology.
AB  - Anorectal physiology, as assessed in an ARP laboratory, can provide helpful
      information in the management of patients with constipation and bowel
      incontinence. Beyond the uses described in this review, however, the ARP
      laboratory is most useful in the research setting. In this setting the laboratory
      can expand our understanding of function associated with other disease states,
      including anal fissure, fistula-in-ano, inflammatory bowel disease, and
      postoperative states. The lab can also provide improved understanding of the
      complex interactions of the enteric nervous and gut hormone systems with the
      smooth and skeletal muscle systems. A part of the failure of the ARP laboratory
      to enjoy more clinical usefulness lies in a lack of standardization of test
      protocols for many of the tests. Secondarily, there is a lack of normative data
      from large numbers of normal patients [1]. Finally, there is the difficulty in
      reproducing tests in situations where the patient has significant potential to
      compensate for deficits through the recruitment of adjacent muscle groups and
      other maneuvers. There is also some reluctance on the part of clinicians to make
      use of the ARP laboratory if the testing is not readily available in their
      community. Although the tests themselves are not difficult to learn to
      administer, lack of familiarity with the testing process can act as a barrier to
      acceptance. This is particularly true for clinicians that are used to making
      clinical decisions without the added benefit of physiologic testing. Despite
      these obstacles, the role of the ARP laboratory in the management of complex
      anorectal disease is likely to grow in the years ahead.

PMID- 12516843
TI  - Anorectal anatomy.
AB  - A working knowledge of anorectal and pelvic anatomy is crucial for the
      understanding of normal function, pathogenesis and surgical treatment of
      anorectal diseases. In a field of unlimited details and varying definitions, our
      goal is to provide an overview of anatomic concepts relevant for the practical
      management of patients.

PMID- 12516844
TI  - Anorectal abscess fistula: what do we know?
AB  - Anorectal abscess and fistula are intimately connected in anatomy, etiology, and
      morbidity. They have been extensively described, but only sparingly studied in
      randomized controlled trials. These trials, covering such issues as primary
      suture of abscess, whether or not to perform a fistulotomy at the time of abscess
      drainage, and comparison of fistulotomy and fistulectomy, are the focus of this
      article. Important gaps in our knowledge and subjects for new trials are also
      discussed.

PMID- 12516845
TI  - Hemorrhoids.
AB  - Technologic advances have contributed to numerous diverse approaches to the
      management of hemorrhoid disease over the past centuries. Better understanding of
      the pathophysiology and anatomy of the anal canal has also added to the increased
      success in the treatment of hemorrhoids. This article reviews the clinical and
      pathological aspects of hemorrhoid disease, emphasizing new therapeutic
      modalities.

PMID- 12516846
TI  - Pilonidal disease.
AB  - Pilonidal disease is a disease of young people, usually men, which can result in
      an abscess, draining sinus tracts, and moderate debility for some. It probably
      results from hair penetration beneath the skin, for reasons that are not totally
      clear. Therapy should be simple, inflict minimal pain, have a short
      hospitalization, have a low recurrence rate, require minimal wound care, and
      allow rapid return to normal activity. No treatment meets all these ideal goals.
      Therefore, starting with a simple treatment and progressing to other treatments
      if failure occurs despite meticulous wound care and hair shaving is the logical
      approach. Table 1 depicts treatments from simple to more complex.

PMID- 12516847
TI  - Hidradenitis suppurativa.
AB  - Hidradenitis suppurativa is a chronic, debilitating disease of apocrine gland
      bearing skin. Its management must be individualized according to the site and
      extent of the disease. Initial conservative measures with antibiotics, local
      wound care, and limited incision and drainage can alleviate the acute symptoms,
      but more radical surgery will likely eventually be necessary in order to control
      and prevent recurrent disease. Options include unroofing and marsupialization,
      local excision, or more extensive operative excision with primary or secondary
      closure, skin grafting, or flap coverage of defects. Wide excision will offer the
      most definitive therapy, with the trade-off being a higher morbidity. Split
      thickness skin grafts in the anal canal may contract and result in anal stenosis
      and should be avoided. Perianal disease is often best managed with local excision
      alone, with primary closure for small defects, and either unroofing or healing by
      secondary intention for larger wounds.

PMID- 12516848
TI  - Anal condyloma and HIV-associated anal disease.
AB  - Although there are a large variety of anal diagnoses associated with the HIV
      population, anal condyloma and anal ulcerations make up the vast majority. A
      large percentage of individuals having multiple concurrent pathologies should
      also be noted. Thus, this article concentrates on anal condyloma, anal ulceration
      and HIV, making note of other significant issues.

PMID- 12516849
TI  - Fournier's gangrene.
AB  - Fournier's gangrene can still be a life-threatening condition with a high
      mortality rate. Diagnosis and treatment should be prompt and adequate.
      Radiological studies may help to define the extent of the disease preoperatively
      in cases in which this is unclear. Surgery with extensive debridement of all
      necrotic tissue is the mainstay of treatment.

PMID- 12516850
TI  - Anal stenosis and mucosal ectropion.
AB  - Anal stenosis (AS) or stricture is defined as the loss of compliant natural
      elasticity of the anal opening, which then becomes abnormally tight and fibrous.
      It is a very disabling condition, worsened by the patient's embarrassment, but
      uncommon. The vast majority of cases are secondary to trauma, iatrogeny,
      inflammatory diseases, or neoplasia, or occur postradiation. Depending on the
      severity and level of involvement, AS can be classified as mild, moderate, or
      severe. Due to the rarity of this pathology and the different referral patterns
      among institutions, the etiology ranges widely between published reports. There
      are multiple surgical techniques that have been described for the correction or
      improvement of AS. Moderate or severe AS is the usual indication for operative
      treatment.

PMID- 12516851
TI  - Anal neoplasms.
AB  - A common theme in most anal neoplasms appears to be a delay in diagnosis due to
      confusion with more common, benign conditions. Thus, the clinician must maintain
      a high index of suspicion when evaluating lesions of the anal canal and margin.
      The use of primary chemoradiation for SCC of the anal canal has resulted in
      equivalent, if not superior, local control and survival compared with radical
      surgery, and results in sphincter preservation in over two thirds of cases.
      Nevertheless, abdominoperineal resection still plays an important role in salvage
      of treatment failures, and also for patients who are unlikely to tolerate
      chemoradiation or have pre-existing impaired continence. Recent studies indicate
      that variations in chemotherapeutic agents and radiation technique might
      potentially produce even better results. The prognosis for anorectal melanoma, as
      well as for small cell and undifferentiated tumors, continues to be poor.
      Fortunately, these are relatively rare tumors.

PMID- 12516852
TI  - Anal trauma and foreign bodies.
AB  - Although anal trauma is rare, iatrogenic injury is not uncommon. Immediate
      recognition is vital to a successful outcome and may obviate the need for a
      diverting stoma. Evaluation must include a search for involvement of other
      structures and an evaluation of the anal sphincters. Foreign bodies most often do
      not cause significant anorectal injuries. Extraction of these diverse objects
      requires ingenuity. Superficial injuries may be left open or sutured closed.
      There are number of options for repair of anal sphincter injuries, either
      immediately or in a delayed fashion. A review of the clinical environment will
      dictate the procedure chosen.

PMID- 12516853
TI  - Rectovaginal fistula.
AB  - Rectovaginal fistulas present a distressing problem for the patient and a
      challenge for the treating physician. Successful management must take into
      consideration the etiology of the fistula and the health of both the rectum and
      the patient. Obstetrical fistulas can be treated successfully by local approaches
      transanally or transvaginally. Episioproctotomy may be considered if there is an
      associated sphincter defect. Crohn's related fistulas usually require proctectomy
      if the rectum is severely involved. Local repair can be considered in instances
      where the rectum is relatively healthy and local sepsis has been controlled.
      Radiation-induced fistulas may be secondary to cancer recurrence, which must be
      excluded. If the patient is not a candidate for a radical resectional approach,
      fecal diversion alone should be performed.

PMID- 12516854
TI  - Fecal incontinence.
AB  - The treatment of fecal incontinence is particularly gratifying because the loss
      of fecal control has a devastating effect on a patients lifestyle. One must
      consider the myriad factors that influence bowel control to properly diagnose and
      treat each patient. Physiology testing, particularly the use of ultrasound, is
      essential when treatment extends beyond dietary and medical management. Recent
      reports suggest that the success of typical treatments may diminish with time.
      This may indicate a greater need in the future for innovative options such as the
      artificial bowel sphincter or sacral stimulation.

PMID- 12516855
TI  - Anal fissure.
AB  - Anal fissure is a common condition with a characteristic presentation. Despite
      increased pharmaceutical options in the medical management of anal fissures,
      surgical therapy is not in danger of becoming obsolete. Lateral internal
      sphincterotomy remains an attractive option for many patients suffering from this
      painful condition.

PMID- 12516856
TI  - Physical methods.
AB  - Despite the advent of high-output, recombinant DNA-based screening strategies,
      many important protein-protein interactions in the plant cell have been and still
      are revealed using co-sedimentation, affinity chromatography and other affinity
      techniques, co-immunoprecipitation and cross-linking. The advantages of these
      techniques, the care that should be taken interpreting the data obtained and the
      possible ways to overcome pitfalls are illustrated.

PMID- 12516857
TI  - Phage display: practicalities and prospects.
AB  - Phage display is a molecular technique by which foreign proteins are expressed at
      the surface of phage particles. Such phage thereby become vehicles for expression
      that not only carry within them the nucleotide sequence encoding expressed
      proteins, but also have the capacity to replicate. Using phage display vast
      numbers of variant nucleotide sequences may be converted into populations of
      variant peptides and proteins which may be screened for desired properties. It is
      now some seventeen years since the first demonstration of the feasibility of this
      technology and the intervening years have seen an explosion in its applications.
      This review discusses the major uses of phage display including its use for
      elucidating protein interactions, molecular evolution and for the production of
      recombinant antibodies.

PMID- 12516858
TI  - Analysing protein-protein interactions with the yeast two-hybrid system.
AB  - Plant research is moving into the post-genomic era. Proteomic-based strategies
      are now being developed to study functional aspects of the genes predicted from
      the various genome-sequencing initiatives. All biological processes depend on
      interactions formed between proteins and the mapping of such interactions on a
      global scale is providing interesting functional insights. One of the techniques
      that has proved itself invaluable in the mapping of protein-protein interactions
      is the yeast two-hybrid system. This system is a sensitive molecular genetic
      approach for studying protein-protein interactions in vivo. In this review we
      will introduce the yeast two-hybrid system, discuss modifications of the system
      that may be of interest to the plant science community and suggest potential
      applications of the technology.

PMID- 12516859
TI  - Imaging protein-protein interactions in living cells.
AB  - The complex organization of plant cells makes it likely that the molecular
      behaviour of proteins in the test tube and the cell is different. For this
      reason, it is essential though a challenge to study proteins in their natural
      environment. Several innovative microspectroscopic approaches provide such
      possibilities, combining the high spatial resolution of microscopy with
      spectroscopic techniques to obtain information about the dynamical behaviour of
      molecules. Methods to visualize interaction can be based on FRET (fluorescence
      detected resonance energy transfer), for example in fluorescence lifetime imaging
      microscopy (FLIM). Another method is based on fluorescence correlation
      spectroscopy (FCS) by which the diffusion rate of single molecules can be
      determined, giving insight into whether a protein is part of a larger complex or
      not. Here, both FRET- and FCS-based approaches to study protein-protein
      interactions in vivo are reviewed.

PMID- 12516860
TI  - Protein-protein interactions in the secretory pathway, a growing demand for
      experimental approaches in vivo.
AB  - The function of the secretory pathway is dependent on multiple protein-protein
      interactions at various stages. Currently, such interactions are mainly studied
      using physical methods that document direct contact or affinity in vitro. The
      development of vital fluorescence imaging as well as quantitative protein
      transport assays opens up the implementation of in vivo approaches which can be
      used to verify models based on in vitro work. The purpose of this review is to
      provide an overview of the various approaches involving living cells to resolve
      interactions between proteins that control complex mechanisms. In particular, it
      is illustrated how combinations of several methods can establish whether
      postulated interactions are of biological relevance or due to artefacts inherent
      to the experimental set-up.

PMID- 12516861
TI  - BP-80 as a vacuolar sorting receptor.

PMID- 12516862
TI  - The plant cytoskeleton: recent advances in the study of the plant microtubule
      associated proteins MAP-65, MAP-190 and the Xenopus MAP215-like protein, MOR1.
AB  - The microtubule cytoskeleton is a dynamic filamentous structure involved in many
      key processes in plant cell morphogenesis including nuclear and cell division,
      deposition of cell wall, cell expansion, organelle movement and secretion. The
      principal microtubule protein is tubulin, which associates to form the wall of
      the tubule. In addition, various associated proteins bind microtubules either to
      anchor, cross-link or regulate the microtubule network within cells. Biochemical,
      molecular biological and genetic approaches are being successfully used to
      identify these microtubule-associated proteins (MAPs) in plants, and we describe
      recent progress on three of these proteins.

PMID- 12516864
TI  - Protein-protein interactions required during translation.
AB  - Protein synthesis requires the involvement of numerous accessory factors that
      assist the ribosome in translation initiation, elongation, and termination.
      Extensive protein-protein and protein-RNA interactions are required to bring
      together the accessory factors, tRNAs, ribosomes, and mRNA into a productive
      complex and these interactions undergo dynamic alterations during each step of
      the translation initiation process. Initiation represents the most complex aspect
      of translation, requiring more accessory proteins, called initiation factors,
      than either elongation or termination. Not surprisingly, initiation is most often
      the rate-limiting step of translation and, as such, most (but not all) examples
      of translational regulation involve the regulation of protein-protein or protein
      RNA interactions of the initiation complex. In this review, we focus on those
      interactions required for efficient translation initiation and how such
      interactions are regulated by developmental or environmental signals.

PMID- 12516865
TI  - Protein complexes mediate signalling in plant responses to hormones, light,
      sucrose and pathogens.
AB  - Living organisms use complex pathways of signal perception and transduction to
      respond to stimuli in their environments. In plants, putative signal transduction
      components have been identified through mutant screens and comparative analysis
      of genome sequences of model eukaryotes. Several pieces in a large series of
      puzzles have now been identified and a current challenge is to determine how
      these pieces interconnect. Functional analysis of the encoded proteins has
      necessitated a change from genetic to biochemical approaches. In recent years,
      the application of techniques such as two-hybrid screening and epitope tagging
      has facilitated the study of protein-protein interactions and has increased our
      understanding of cellular signalling mechanisms. One focus of present research is
      the ubiquitin/proteasome-mediated degradation of proteins. Increasing evidence
      suggests this is a control common to many plant signalling pathways including
      development and responsiveness to hormones, light and sucrose. A central
      challenge in the study of plant disease resistance has been to identify protein
      complexes that contain host defence proteins and pathogenicity factors. In this
      review we summarize the latest developments in these areas where the existence of
      protein complexes has been demonstrated to be of fundamental importance in plant
      signalling.

PMID- 12516863
TI  - Multi-protein complexes in eukaryotic gene transcription.
AB  - Specific transcription initiation by RNA polymerase II at eukaryotic protein
      coding genes involves the cooperative assembly at the core promoter of more than
      40 distinct proteins--with a total mass of over 2 MDa--including RNA polymerase
      II itself and general/basal transcription initiation factors, to form a stable
      pre-initiation complex (PIC). In vivo, PIC assembly is a major point of
      regulation by sequence-specific transcription regulators (activators and
      repressors) and is hindered by the packaging of promoter DNA into nucleosomes and
      higher order chromatin structures. Genetic and biochemical studies have recently
      identified a variety of transcription cofactors/co-regulators (coactivators and
      corepressors) that interact with sequence-specific regulators and/or various
      components of the general/basal transcription machinery and are essential for
      regulated transcription. An emerging view from these studies is that regulators
      must target two types of transcription cofactors: chromatin-modifying/remodeling
      cofactors and general cofactors that associate with and/or influence the
      activities of components of the general/basal transcription machinery. The recent
      biochemical identification and characterization of many different chromatin
      modifying and general transcription cofactors has revealed their often complex
      multi-subunit nature and a previously unsuspected level of structural and
      functional redundancy. Another emerging theme is the multi-functional nature of
      chromatin-modifying cofactor complexes that appear to couple gene-specific
      transcription to other cellular processes.

PMID- 12516866
TI  - Protein-protein interactions in pathogen recognition by plants.
AB  - Protein-protein interactions have emerged as key determinants of whether plant
      encounters with pathogens result in disease or successful plant defense. Genetic
      interactions between plant resistance genes and pathogen avirulence genes enable
      pathogen recognition by plants and activate plant defense. These gene-for-gene
      interactions in some cases have been shown to involve direct interactions of the
      products of the genes, and have indicated plant intracellular localization for
      certain avirulence proteins. Incomplete specificity of some of the interactions
      in laboratory assays suggests that additional proteins might be required to
      confer specificity in the plant. In many cases, resistance and avirulence protein
      interactions have not been demonstrable, and in some cases, other plant
      components that interact with avirulence proteins have been found. Investigation
      to date has relied heavily on biochemical and cytological methods including in
      vitro binding assays and immunoprecipitation, as well as genetic tools such as
      the yeast two-hybrid system. Observations so far, however, point to the likely
      requirement for multiple, interdependent protein associations in pathogen
      recognition, for which these techniques can be insufficient. This article reviews
      the protein-protein interactions that have been described in pathogen recognition
      by plants, and provides examples of how rapid future progress will hinge on the
      adoption of new and developing technologies.

PMID- 12516867
TI  - Functional specificity in 14-3-3 isoform interactions through dimer formation and
      phosphorylation. Chromosome location of mammalian isoforms and variants.
AB  - 14-3-3 is now accepted as a novel type of dimeric protein that can modulate
      interaction between proteins involved in cell signalling and other functions.
      Target proteins that interact with 14-3-3 isoforms are involved in regulation of
      cell cycle, intracellular trafficking/targeting, signal transduction,
      cytoskeletal structure and transcription. In many cases, these proteins show a
      distinct preference for a particular isoform(s) of 14-3-3. A specific repertoire
      of dimer formation may influence which of the 14-3-3 interacting proteins could
      be brought together. The purpose of this review is to give an overview of
      mammalian 14-3-3 sequences, structures and post-translational modifications that
      may explain the known interactions with other proteins and mechanism(s). The
      regulation of interaction may involve phosphorylation of the interacting protein
      and in some cases the phosphorylation of 14-3-3 isoforms themselves.

PMID- 12516868
TI  - Evolution and isoform specificity of plant 14-3-3 proteins.
AB  - The 14-3-3 proteins, once thought of as obscure mammalian brain proteins, are
      fast becoming recognized as major regulators of plant primary metabolism and of
      other cellular processes. Their presence as large gene families in plants
      underscores their essential role in plant physiology. We have examined the
      Arabidopsis thaliana 14-3-3 gene family, which currently is the largest and most
      complete 14-3-3 family with at least 12 expressed members and 15 genes from the
      now completed Arabidopsis thaliana genome project. The phylogenetic branching of
      this family serves as the prototypical model for comparison with other large
      plant 14-3-3 families and as such may serve to rationalize clustering in a
      biological context. Equally important for ascribing common functions for the
      various 14-3-3 isoforms is determining an isoform-specific correlation with
      localization and target partnering. A summary of localization information
      available in the literature is presented. In an effort to identify specific 14-3
      3 isoform location and participation in cellular processes, we have produced a
      panel of isoform-specific antibodies to Arabidopsis thaliana 14-3-3s and present
      initial immunolocalization studies that suggest biologically relevant,
      discriminative partnering of 14-3-3 isoforms.

PMID- 12516869
TI  - 14-3-3 proteins and plant development.
AB  - The 14-3-3 proteins are a family of ubiquitous regulatory molecules which have
      been found in virtually every eukaryotic organism and tissue. Discovered 34 years
      ago, 14-3-3 proteins have first been studied in mammalian nervous tissues, but in
      the past decade their indispensable role in various plant regulatory and
      metabolic pathways has been increasingly established. We now know that 14-3-3
      members regulate fundamental processes of nitrogen assimilation and carbon
      assimilation, play an auxiliary role in regulation of starch synthesis, ATP
      production, peroxide detoxification, and participate in modulation of several
      other important biochemical pathways. Plant development and seed germination
      appear also to be under control of factors whose interaction with 14-3-3
      molecules is crucial for their activation. Located within the nucleus, 14-3-3
      isoforms are constituents of transcription factor complexes and interact with
      components of abscisic acid (ABA)-induced gene expression machinery. In addition,
      in animal cells they participate in nucleo-cytoplasmic trafficking and molecular
      sequestration. Cytoplasmic 14-3-3 members form a guidance complex with
      chloroplast destined preproteins and facilitate their import into these
      photosynthetic organelles. Recently, several 14-3-3s have been identified within
      chloroplasts where they could be involved in targeting and insertion of thylakoid
      proteins. The identification of 14-3-3 isoform specificity, and in particular the
      elucidation of the signal transduction mechanisms connecting 14-3-3 members with
      physiological responses, are central and developing topics of current research in
      this field.

PMID- 12516870
TI  - 14-3-3 proteins and the response to abiotic and biotic stress.
AB  - 14-3-3 proteins function as regulators of a wide range of target proteins in all
      eukaryotes by effecting direct protein-protein interactions. Primarily,
      interactions between 14-3-3 proteins and their targets are mediated by
      phosphorylation at specific sites on the target protein. Hence, interactions with
      14-3-3s are subject to environmental control through signalling pathways which
      impact on 14-3-3 binding sites. Because 14-3-3 proteins regulate the activities
      of many proteins involved in signal transduction, there are multiple levels at
      which 14-3-3 proteins may play roles in stress responses in higher plants. In
      this article, we review evidence which implicates 14-3-3 proteins in responses to
      environmental, metabolic and nutritional stresses, as well as in defence
      responses to wounding and pathogen attack. This evidence includes stress
      inducible changes in 14-3-3 gene expression, interactions between 14-3-3 proteins
      and signalling proteins and interactions between 14-3-3 proteins and proteins
      with defensive functions.

PMID- 12516871
TI  - 14-3-3 protein regulation of proton pumps and ion channels.
AB  - In addition to their regulation of cytoplasmic enzymes, the 14-3-3 proteins are
      important regulators of membrane localised proteins. In particular, many of the
      cells' ion pumps and channels are either directly or indirectly modulated by 14-3
      3 proteins. Binding of 14-3-3 can lead to the activation of pump activity as in
      the case of the plasma membrane H+-ATPase or inhibition as in the case of the F
      type ATP synthase complexes. 14-3-3 binding can also lead to surprising results
      such as the recruitment of 'sleepy' outward rectifiying K+ channels in tomato
      cells. Our present knowledge extends to an initial understanding of isoform
      specific binding of 14-3-3 to certain membrane proteins and a perception of the
      protein kinases and phosphatases that maintain the regulatory process in a state
      of flux.

PMID- 12516873
TI  - Enhancement of lindane-induced liver oxidative stress and hepatotoxicity by
      thyroid hormone is reduced by gadolinium chloride.
AB  - The role of Kupffer cells in the hepatocellular injury and oxidative stress
      induced by lindane (20 mg/kg; 24h) in hyperthyroid rats (daily doses of 0.1 mg L
      3,3',5-triiodothyronine (T3)/kg for three consecutive days) was assessed by the
      simultaneous administration of gadolinium chloride (GdCl3; 2 doses of 10mg/kg on
      alternate days). Hyperthyroid animals treated with lindane exhibit enhanced liver
      microsomal superoxide radical (O2.-) production and NADPH cytochrome c reductase
      activity, with lower levels of cytochrome P450, superoxide dismutase (SOD) and
      catalase activity, and glutathione (GSH) content over control values. These
      changes are paralleled by a substantial increase in the lipid peroxidation
      potential of the liver and in the O2.- generation/ SOD activity ratio, thus
      evidencing a higher oxidative stress status that correlates with the development
      of liver injury characterized by neutrophil infiltration and necrosis. Kupffer
      cell inactivation by GdCl3 suppresses liver injury in lindane/T3-treated rats
      with normalization of altered oxidative stress-related parameters, excepting the
      reduction in the content of GSH and in catalase activity. It is concluded that
      lindane hepatotoxicity in hyperthyroid state, that comprises an enhancement in
      the oxidative stress status of the liver, is largely dependent on Kupffer cell
      function, which may involve generation of mediators leading to pro-oxidant and
      inflammatory processes.

PMID- 12516874
TI  - Differential expression of glutathione reductase and cytosolic glutathione
      peroxidase, GPX1, in developing rat lungs and kidneys.
AB  - A mutant rat GPX1 (a cytosolic predominant form), in which the selenocysteine
      residue in the catalytic center was replaced by cysteine, was prepared and an
      antibody against the mutant enzyme was raised. The resultant antibody
      specifically reacted with rat GPX1 and was, together with the Glutathione
      reductase (GR) antibody, used in a Western blot analysis and immunohistochemistry
      experiments. To elucidate the physiological coupling of these enzymes under
      oxidative stress which accompanies the birth, developmental changes of the
      protein levels and enzymatic activities of GR and GPX1 were examined for lungs
      and kidneys from prenatal fetus to adult rats. The expression of GR was already
      evident at the prenatal stage and remained high in lungs at all stages. However,
      GR activity in kidneys gradually increased after birth reaching maximal levels at
      adulthood. An immunohistochemical study showed that GR was strongly bound to the
      bronchial epithelia in lungs and the epithelial cells of renal tubes. GPX1 was
      expressed in the renal tube epithelial cells and its level gradually increased
      after birth in a manner similar to that of GR. The expression of GPX1 in the
      lungs was, on the other hand, variable and occurred in some alveolar cells and
      bronchial epithelia only at restricted periods. It preferentially localized in
      nuclei at a late stage of development. Thus, the expression of the two
      functionally coupled enzymes via GSH did not appear to coordinate with
      development, tissue localization or under oxidative stress. Since many gene
      products show GSH-dependent preoxidase activity, other peroxidase(s) may be
      induced to compensate for the low GPX1 levels at stages with high GR expression.

PMID- 12516872
TI  - Metabolic enzymes as targets for 14-3-3 proteins.
AB  - The 14-3-3 proteins are binding proteins that have been shown to interact with a
      wide array of enzymes involved in primary biosynthetic and energy metabolism in
      plants. In most cases, the significance of binding of the 14-3-3 protein is not
      known. However, most of the interactions are phosphorylation-dependent and most
      of the known binding partners are found in the cytosol, while some may also be
      localized to plastids and mitochondria. In this review, we examine the factors
      that may regulate the binding of 14-3-3s to their target proteins, and discuss
      their possible roles in the regulation of the activity and proteolytic
      degradation of enzymes involved in primary carbon and nitrogen metabolism.

PMID- 12516875
TI  - Teratogenic actions of thermally-stressed culinary oils in rats.
AB  - Lipid oxidation products (LOPs), generated in culinary oils during episodes of
      thermal stressing can give rise to cellular damage. The aims of this study were
      to determine whether orally-administered, LOP-containing thermally-stressed
      safflower oil exerts teratogenic actions in rats, and whether this effect could
      be prevented by co-administration of alpha-tocopherol (alpha-TOH). Safflower oil
      was heated for a period of 20 min according to standard frying practices and
      stored at -20 degrees C under N2. Four experimental groups of pregnant Wistar
      rats were employed; two received 0.30 ml of pre-heated oil (HO), one of which was
      also supplemented with 150 mg of alpha-TOH (HOE), and two served as controls, one
      treated with the non-heated oil (O) and the other without any treatment (C). The
      oil was administered daily by gavage from day 1 of pregnancy to day 11.5, when
      the animals were killed and the embryos examined. LOPs and alpha-TOH were
      determined both in the heated and non-heated oils. The percentage of embryo
      malformations and reabsorptions were determined in the above four experimental
      groups. Heating the oil substantially increased its concentration of LOPs and
      decreased its alpha-TOH content. The percentage of embryo malformations in the HO
      group was 21.73%, compared with 5.6 and 7% in the O and C groups, respectively.
      Supplementation of the pre-heated oil with alpha-TOH was found to decrease the
      percentage of malformations to 7%. The results obtained from these investigations
      indicate that LOPs detectable at millimolar levels in the heated cooking oils
      administered (e.g. saturated and alpha,beta-unsaturated aldehydes, and/or their
      conjugated hydroperoxydiene precursors) exert potent teratogenic actions in
      experimental animals which are at least partially circumventable by co
      administration of the chain-breaking antioxidant alpha-TOH. Plausible mechanisms
      for these processes and their health relevance to humans regarding diet and
      methods of frying/cooking are discussed.

PMID- 12516876
TI  - Production of hydroxyl radicals and alpha-dicarbonyl compounds associated with
      Amadori compound-Cu2+ complex degradation.
AB  - The chemical properties of Amadori compounds in the presence of transition metal
      ions were studied, using the analogs 1-deoxy-1-n-butylamino-D-fructose (DBF) and
      N(alpha)-formyl-fructoselysine (fFL). The following characteristics were
      revealed: (a) DBF combined easily with Cu2+ (but no other transition metal ions)
      to form a DBF-Cu2+ complex in phosphate buffer, pH 7.4; (b) the complex was
      unstable, and degraded with the release of Cu+ during incubation at 37 degrees C;
      (c) degradation of the complex was associated with the production of hydroxyl
      radicals by the Fenton reaction and alpha-dicarbonyl compounds by non
      autoxidative degradation; and (d) properties of DBF were similar to those of fFL.
      The above properties were additionally observed in glycated poly-Lys (GPL). Our
      findings indicate a novel mechanism for the generation of hydroxyl radicals and a
      dicarbonyl compounds from Amadori adducts in the presence of Cu2+.

PMID- 12516877
TI  - Effects of parenteral lipid infusion on DNA damage in very low birth weight
      infants.
AB  - Very low birth weight (VLBW) infants are known to have poorly developed
      antioxidant system and may be at increased risk for radical damage. Previous
      studies have reported higher levels of lipid peroxide products in lipid emulsion
      used for parenteral nutrition. To examine the direct effects of parenteral lipid
      infusion on DNA damage in VLBW infants, we measured urinary 8
      hydroxydeoxyguanosine (8-OHdG) levels in VLBW infants before, during, and after
      the parenteral lipid infusion. In both the lipid-infused and lipid-free groups,
      urinary 8-OHdG excretion levels at 14 days old were significantly (p < 0.01)
      lower than those at 2 and 7 days old. However, there were no significant
      differences in urinary 8-OHdG excretion levels between the lipid-infused and
      lipid-free groups at 2, 7, and 14 days old. Our results suggest that parenteral
      lipid infusion does not cause oxidative DNA damage, but irrespective of the
      infusion DNA damage during the first week of life is enhanced when compared with
      14 days after birth in VLBW infants.

PMID- 12516878
TI  - Inhibition of lipid peroxidation by S-nitrosoglutathione and copper.
AB  - The antioxidant properties of S-nitrosoglutathione, a nitric oxide-derived
      product were studied in different experimental systems. By using the crocin
      bleaching test, S-nitrosoglutathione, in the presence of copper ions, shows an
      antioxidant capacity about six times higher than that of Trolox c and referable
      to the interception of peroxyl radicals by nitric oxide. Copper alone shows a
      modest inhibitory action, which is about seven times lower than that of Trolox c.
      S-nitrosoglutathione prevents lipid peroxidation induced by the well-known
      Fe2+/ascorbate system (IC50 = 450 microM) and the inhibitory effect is strongly
      reinforced by the presence of copper ions (IC50 = 6.5 microM). In addition,
      cumene hydroperoxide-induced lipid peroxidation is markedly decreased by S
      nitrosoglutathione, provided that copper ions, maintained reduced by ascorbate,
      are present. Decomposition of S-nitrosoglutathione through metal catalysis and/or
      the presence of reducing agents and the consequent release of nitric oxide are of
      crucial importance for eliciting the antioxidant power. In this way, copper ions
      and/or reducing species with low antioxidant potency are able to promote the
      formation of an extremely strong antioxidant species such as nitric oxide.

PMID- 12516879
TI  - Increased release of free Fe ions in human erythrocytes during aging in the
      circulation.
AB  - We investigated whether free Fe ions were released in erythrocytes during aging
      process in the circulation. Young and senescent erythrocytes were separated from
      freshly drawn human blood by Percoll density gradient centrifugation. Two
      different methods were employed for determination of free Fe ions in
      erythrocytes, desferrioxamine (DFO) method and bleomycin method. DFO-chelatable
      Fe ions were detected in whole erythrocytes from 2 donors, and the DFO-chelatable
      free Fe ion levels in senescent erythrocytes were higher than those in young
      erythrocytes. Bleomycin-sensitive Fe ions, which was rather lower than DFO
      chelatable Fe ions, were also detected in whole erythrocytes from 5 donors, and
      the free Fe ion levels in senescent erythrocytes were also higher than those in
      young erythrocytes. Free Fe ions may be derived from oxidative damage of
      hemoglobin, because treatment of whole erythrocytes or purified oxyhemoglobin
      with hydrogen peroxide gave increased free Fe ions. The results indicated that
      free Fe ions were released from erythrocytes during aging process in the
      circulation. Released free Fe ions would promote oxidative damages of the cells
      during aging process.

PMID- 12516880
TI  - Effect of rhinovirus challenge on antioxidant enzymes in respiratory epithelial
      cells.
AB  - The host inflammatory response appears to be an important contributor to the
      pathogenesis of human viral respiratory illness. Virus-induced oxidative stress
      appears to mediate an early phase of elaboration of the proinflammatory cytokine
      interleukin-8 by respiratory epithelial cells. The purpose of these studies was
      to determine if virus-induced alterations in either the expression or function of
      antioxidant enzymes contributes to the cellular oxidative stress following
      rhinovirus challenge. The activities of Mn superoxide dismutase (MnSOD), catalase
      and glutathione peroxidase (GPX) were not significantly changed by rhinovirus
      challenge. CuZn superoxide dismutase (CuZnSOD) activity six hours after challenge
      was 2.55 +/- 0.56 U/mg protein in rhinovirus-challenged cells compared to 1.16 +/
      0.54 U/mg protein in control cells (p = 0.029). This increased activity was
      associated with a concomitant increase in CuZnSOD mRNA and protein concentration.
      These data suggest that rhinovirus-induced changes in the host cell redox state
      that result in the early elaboration of interleukin-8 are not mediated by
      inhibition of either the expression or function of these antioxidant enzymes.

PMID- 12516881
TI  - Effects of trientine, a metal chelator, on defective endothelium-dependent
      relaxation in the mesenteric vasculature of diabetic rats.
AB  - Diabetes mellitus compromises endothelium-dependent relaxation of blood vessels.
      This has been linked to the generation of reactive oxygen species (ROS), which
      neutralise nitric oxide (NO) and interfere with vasodilator function. Experiments
      using chelators have emphasised the importance of ROS produced by transition
      metal catalysed reactions. However, particularly for the small arteries and
      arterioles that control microcirculatory blood flow, NO is not the only
      endothelium-derived mediator; endothelium-derived hyperpolarizing factor (EDHF)
      has a major role. EDHF-mediated vasodilation is severely curtailed by diabetes;
      however, little information exists on the underlying pathophysiology. Deficits in
      the EDHF system, alone or in combination with the NO system, are crucial for the
      development of diabetic microvascular complications. To further elucidate the
      mechanisms involved, the aim was to examine the effects of diabetes and
      preventive and intervention chelator therapy with trientine on a preparation that
      has well-defined NO and EDHF-mediated responses, the rat mesenteric vascular bed.
      In phenylephrine-preconstricted preparations, maximum vasodilation to
      acetylcholine was reduced by 35 and 44% after 4 and 8 weeks of streptozotocin
      induced diabetes, respectively. Trientine treatment over the first 4 weeks gave
      72% protection; intervention therapy over the final 4 weeks prevented
      deterioration and corrected the initial deficit by 68%. These responses depend on
      both NO and EDHF. When the latter mechanism was isolated by NO synthase
      inhibition, diabetic deficits of 53.4 (4 weeks) and 65.4% (8 weeks) were
      revealed, that were 65% prevented and 50% corrected by trientine treatment.
      Neither diabetes nor trientine altered vascular smooth muscle responses to the NO
      donor, sodium nitroprusside (SNP). Thus, the data suggest that metal catalysed
      ROS production makes a substantial contribution to defects in both the EDHF and
      NO endothelial mechanisms in diabetes, which has therapeutic implications for
      microvascular complications.

PMID- 12516882
TI  - Acute phase immune response to exercise coexists with decreased neutrophil
      antioxidant enzyme defences.
AB  - Long-duration or damaging exercise initiates reactions that resemble the acute
      phase response to infection and induces neutrophil priming for oxidative
      activity. Our objective was to establish the status of the antioxidant defences
      and of the oxidative equilibrium in the neutrophils of sportsmen prior to and
      after intense physical exercise. Nine voluntary male professional cyclists
      participated in this study. The exercise was a cycling mountain stage (171 km)
      and the cyclists took a mean +/- SEM of 270 +/- 12 min to complete it. We
      determined the activities of catalase (CAT), glutathione reductase (GR),
      glutathione peroxidase (GPx), the levels and activity of superoxide dismutase
      (SOD), the concentrations of ascorbate, glutathione and glutathione disulphide
      (GSSG) and DNA levels in neutrophils. The cycling stage decreased enzyme
      activities expressed per DNA units: CAT (33%), SOD (38%), GPx (65%); increased
      ascorbate concentration in neutrophils and decreased the GSH/GSSG ratio and the
      enzyme activities expressed per DNA units. Neutrophils could contribute to plasma
      antioxidant defences against oxidative stress induced by exercise because they
      probably provide antioxidant enzymes and ascorbate.

PMID- 12516883
TI  - Oxygen availability as a possible limiting factor in LDL oxidation.
AB  - Kinetic studies of copper-induced LDL peroxidation commonly assume that the
      availability of molecular oxygen in the reaction media is not a limiting factor.
      The present study reveals that this assumption is valid only at low LDL
      concentrations. At high LDL concentrations, accumulation of oxidation products,
      as monitored spectroscopically under conditions of various oxygen concentrations
      in the medium, comes to a halt when the oxygen concentration in the solution, as
      measured by an oxygen electrode, decreases to near zero levels. Bubbling of the
      oxygen into the solution results in resumption of peroxidation. These results are
      important with respect to the ex vivo assaying of lipoprotein peroxidation
      because many previous studies have been conducted with LDL concentrations that
      corresponded to polyunsaturated fatty acid concentrations in access of the
      concentration of molecular oxygen. The possible pathophysiological significance
      of the results of this study has yet to be evaluated.

PMID- 12516884
TI  - Local pharmacokinetic analysis of a stable spin probe in mice by in vivo L-band
      ESR with surface-coil-type resonators.
AB  - In vivo ESR spectroscopy using a low frequency microwave of approximately 1 GHz
      has been developed to measure non-invasive ESR spectra in animals given
      paramagnetic compounds, in which a loop-gap-type resonator was used and ESR
      spectra were measured at the animal's head or abdomen. Therefore, the
      concentrations of paramagnetic species in both the blood and organs were
      compositely contributed to the spectra. When we understand the kinetics of
      paramagnetic species in detail, it is essentially important to know how these
      kinetics are expressed in each organ. For this purpose, a surface-coil-type
      resonator, which enabled local ESR measurement in specific organs, has been
      developed. By using this method, we studied the real-time pharmacokinetics of
      spin clearance curves detected in the organs of mice given 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl (4-hydroxy-TEMPO) intravenously (i.v.), by
      monitoring the inferior vena cava, liver and kidney. Quantified dearance curves
      in the organs were analyzed on the basis of a two-compartment model, and
      pharmacokinetic parameters were estimated based on the curve-fitting. The
      obtained pharmacokinetic parameters were found to depend on the measurement site,
      and the distribution and elimination processes of the spin probe were
      successfully separated between the blood and organs of mice.

PMID- 12516885
TI  - Black tea represents a major source of dietary phenolics among regular tea
      drinkers.
AB  - The phenolic composition and antioxidant activities [TEAC, ORAC, FRAP] of
      consumer brews (1 tea bag in 230 ml for 1 min) of seven different brands of black
      tea from the British market were investigated. The main phenolic compounds
      identified were epigallocatechin gallate, four theaflavins, as well as
      epicatechin gallate, theogallin (tentative assignment), quercetin-3-rutinoside
      and 4-caffeoyl quinic acid. Thearubigins represented an estimated 75-82% of the
      total phenolics. Further, polyphenol fractions were in decreasing order
      theaflavins, flavan-3-ols, flavonols, gallic acids and hydroxycinnamates. On
      average, a cup of a consumer brew of black tea is providing polyphenols at the
      level of 262mg GAE/serving, of which 65 mg were assigned to individual
      polyphenols. The antioxidant activity of black tea preparations is higher than
      that of most reported dietary agents on a daily basis. Correlations were observed
      between the antioxidant activities and the sum of all quantified polyphenols by
      HPLC analysis as well as with the total phenolics. Treatment of the black tea
      brew with simulated gastric juice resulted in a significant increase of the
      identified theaflavins implying a partial cleavage of thearubigins in the
      environment of the gastric lumen. Therefore, black tea can be considered to be a
      rich source of polyphenols and/or antioxidants.

PMID- 12516886
TI  - Pharmacology of systemic analgesics.
AB  - Systemic administration of analgesic drugs is still the most widely used method
      for providing pain relief in acute painful situations. Opioids may be selected on
      the basis of their physicochemical characteristics and their diffusion index to
      the brain. But in clinical practice, their very steep concentration-analgesic
      effect relationship remains a critical aspect of opioid therapy. Thus, small
      fluctuations in plasma concentrations of opioids may lead to profound
      fluctuations in analgesic effect when their plasma and effect-site concentrations
      are near the minimum effective analgesic concentration (MEAC). Combining drugs
      acting on different mechanisms of nociceptive modulation offers benefits from
      additive/synergistic effects and will decrease the incidence of their adverse
      effects. Evidence-based reviews showed that effective pain relief using non
      opioid analgesics relied on paracetamol supplemented with non-steroidal anti
      inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in
      acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol
      share the property of morphine sparing in situations of severe (post-operative)
      pain. CSIs may be beneficial in patients in whom post-operative bleeding is a
      major surgical risk as the effects of NSAIDs on coagulation may last for days.
      Finally, low-dose ketamine infusions remain a worthwhile addition to opioid
      therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic
      concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA)
      receptor activation.

PMID- 12516887
TI  - Understanding the physiology and pharmacology of epidural and intrathecal
      opioids.
AB  - Epidural and intrathecal opioid administration has become an important part of
      contemporary medical practice in a variety of clinical settings. It has been
      widely assumed that any opioid placed in the epidural or intrathecal spaces will
      produce highly selective spinally mediated analgesia that is superior to that
      produced by other analgesic techniques. Unfortunately, this is simply not true.
      In fact, multiple opioids are currently employed for spinal use despite the fact
      that clinical evidence has shown that spinal administration does not produce
      analgesia with a selective spinal mechanism or that the analgesia produced is not
      superior to that produced by intravenous administration. This chapter presents
      the basic science and clinical data available to assist clinicians in identifying
      which opioids are appropriate for spinal use and which are not.

PMID- 12516888
TI  - Drug combinations in pain treatment: a review of the published evidence and a
      method for finding the optimal combination.
AB  - The evidence of the usefulness of drug combinations in pain management is
      reviewed and the problem of finding the optimal combination is presented. For
      post-operative pain, adding a non-steroidal anti-inflammatory drug (NSAID) or
      paracetamol to intravenous morphine is beneficial. Adding ketamine to intravenous
      morphine may be advantageous, but ketamine has a narrow therapeutic window. The
      combination paracetamol-NSAID is probably superior to either component alone. For
      post-operative epidural analgesia, combinations of low doses of a local
      anaesthetic, an opioid and adrenaline (epinephrine) are superior to single-drug
      regimens. There are virtually no data on the advantages of combinations over
      single drugs in neuropathic and chronic musculoskeletal pain. Adding NSAIDs or
      ketamine to opioids may be useful in cancer pain. Because of the enormous number
      of possible combinations, randomized controlled trials may fail to test the
      optimal combination. A stepwise optimization model that has been applied in
      clinical investigations is presented.

PMID- 12516889
TI  - Cellular mechanisms of opioid tolerance and the clinical approach to the opioid
      tolerant patient in the post-operative period.
AB  - The high prevalence of opioid use for recreational purposes in the USA and the
      European Union, as well as the use of opioids for the treatment of chronic non
      malignant pain, has resulted in an increase in the number of patients with opioid
      tolerance who undergo surgery and require post-operative pain management. The
      approach to post-operative pain control in these patients is significantly
      different to the strategies used in opioid naive patients. Fortunately, better
      understanding of the cellular mechanisms of opioid tolerance in animals has
      resulted in the transfer of concepts from the 'bench' to the clinical arena. This
      chapter describes the new developments in opioid tolerance and how this knowledge
      can be applied to clinical practice.

PMID- 12516890
TI  - How to implement an acute pain service.
AB  - To implement a successful acute pain service the following factors are the most
      important for success: anaesthesiologist-supervised pain nurses and an ongoing
      educational programme for patients and all health personnel involved in the care
      of surgical patients. The benefits in increased patient satisfaction and improved
      outcome after surgery will far outweigh the costs of running an acute pain
      service that raises standards of pain management throughout the hospital. Optimal
      use of basic pharmacological analgesia will improve relief of post-operative pain
      for most surgical patients. More advanced approaches, such as well-tailored
      epidural analgesia, are needed to relieve severe dynamic pain (e.g. when
      coughing). This may reduce markedly risks of complications in patients at high
      risk of developing post-operative respiratory infections and cardiac ischaemic
      events. More aggressive methods for post-operative pain management need robust
      routines that will discover the early symptoms and signs of potentially serious
      complications. High preparedness must be present for swift and correct handling
      of the rare but potentially catastrophic complications of bleeding and infection
      in the spinal canal. Chronic pain is common after surgery. Better acute pain
      relief may reduce this distressing long-term complication of surgery. Research
      into the long-term effects of optimal neuraxial analgesia and drugs that dampen
      glutamatergic hyperphenomena (hyperalgesia/allodynia) are urgently needed to
      verify whether these approaches can reduce the problem of intractable chronic
      post-operative pain.

PMID- 12516892
TI  - Diagnostic nerve blocks in chronic pain.
AB  - Diagnostic blocks are used to obtain information about the source of a patient's
      pain. As such they differ in principle and in practice from regional anaesthetic
      blocks. In order to be valid, diagnostic blocks must be precise and target
      specific. They must be controlled in order to exclude false-positive responses.
      Sympathetic blocks have traditionally been performed without pharmacological
      controls, but studies have shown that the features of complex regional pain
      syndromes can be relieved equally well when normal saline is administered as when
      local anaesthetic is used. This warns that sympathetic blocks must be controlled
      in each and every case lest false conclusions be drawn about the response. Medial
      branch blocks of the lumbar and of the cervical dorsal rami have been extensively
      investigated in order to establish their validity, diagnostic utility and
      therapeutic utility. They provide an example and benchmark for how diagnostic
      blocks can and should be validated.

PMID- 12516891
TI  - Effect of post-operative analgesia on patient morbidity.
AB  - The pathophysiology that commonly follows surgery results in detrimental
      physiological effects and may be associated with post-operative mortality and
      morbidity. The use of post-operative epidural analgesia, but not systemic
      opioids, may attenuate some of these adverse physiological effects and result in
      a decrease in patient-related morbidity post-operatively. Randomized trials
      suggest that the perioperative use of epidural analgesia may facilitate return of
      gastrointestinal function, attenuate hypercoagulable events and diminish post
      operative pulmonary complications. A multimodal approach incorporating the use of
      epidural analgesia to control perioperative pathophysiology will facilitate the
      patient's recovery.

PMID- 12516893
TI  - Steroid injections: effect on pain of spinal origin.
AB  - Pain originating from the spine is a common clinical problem that is often
      difficult to manage. This chapter considers the evidence supporting the use of
      corticosteroid injections for pain of spinal origin. Clinical problems considered
      in this review are radicular pain, zygapophyseal joint pain, discogenic pain and
      non-specific pain from the cervical, lumbar and thoracic spine. Issues of
      efficacy and adverse events are considered. No useful data were found concerning
      the treatment of any type of thoracic pain with corticosteroid injections. In the
      lumbar spine, there is evidence to support the use of transforaminal injections
      for radicular pain. Intradiscal and intra-articular injections in both lumbar and
      cervical spines have not been shown to be effective. Sacroiliitis responds well
      to intra-articular corticosteroids. There is insufficient evidence to support the
      use of atlanto-axial or atlanto-occipital joint injections.

PMID- 12516894
TI  - Radiofrequency procedures in chronic pain.
AB  - Radiofrequency current is simply a tool used for creating discrete thermal
      lesions in neural pathways in order to interrupt transmission. In pain medicine,
      radiofrequency lesions have been used to interrupt nociceptive pathways at
      various sites. This is a palliative treatment not without complications, so its
      use should be limited to those patients with cancer pain or chronic non-cancer
      pain for whom conservative non-surgical therapies have been ineffective or
      intolerable. With the development of alternatives such as intrathecal opioid
      infusion and neuromodulation technologies, the number of patients considered for
      neuroablative therapy may dwindle. Nevertheless, there is evidence that
      radiofrequency neurotomy has an important role in the management of trigeminal
      neuralgia, nerve root avulsion and spinal pain. In this chapter the evidence for
      efficacy and safety is reviewed and interrogated with special emphasis on the
      available randomized controlled trails and systematic review.

PMID- 12516895
TI  - Implantable devices for pain control: spinal cord stimulation and intrathecal
      therapies.
AB  - Untreated chronic pain is costly to society and to the individual suffering from
      it. The treatment of chronic pain, a multidimensional disease, should rely on the
      expertise of varying health care providers and should focus not only on the
      neurobiological mechanisms of the process but also on the psychosocial aspects of
      the disease. Implantable devices are costly and invasive, and such efficacious
      therapies should be used only when more conservative and less costly therapies
      have failed to provide relief of pain and suffering. Spinal cord stimulation
      provides neuromodulation of neuropathic, but not nociceptive, pain signals and
      when used for appropriate indications in the right individuals provides
      approximately 60-80% long-term pain relief in 60-80% of patients trialled for
      efficacy. Intrathecal therapies with opioids such as morphine, fentanyl,
      sufentanil or meperidine--or non-opioids such as clonidine or bupivacaine-
      provide analgesia in patients with nociceptive or neuropathic pain syndromes.
      Baclofen, intrathecally, provides profound relief of muscle spasticity due to
      multiple sclerosis, spinal cord injuries, brain injuries or cerebral palsy.

PMID- 12516896
TI  - Epidural and intrathecal analgesia for cancer pain.
AB  - The three-step analgesic ladder approach developed by the World Health
      Organization works well in treating the vast majority (70-90%) of patients
      suffering from pain related to cancer. In those patients who do not get pain
      relief by this three-step approach, intraspinal agents can be a fourth step in
      managing pain of malignant origin. Although morphine is the only opioid approved
      by the US Food and Drug Administration for intraspinal use, many different opioid
      analgesics are used intraspinally, including hydromorphone, fentanyl, sufentanil,
      meperidine and methadone in the treatment of cancer pain. Many non-opioid agents
      have also been used intraspinally either alone or in combination with opioids in
      the treatment of intractable cancer pain. This chapter summarizes the clinical
      use of these agents with some practical points.

PMID- 12516897
TI  - From pain research to pain treatment: the role of human experimental pain models.
AB  - There is no objective measure of a complete pain perception; we can, however,
      measure different aspects of nociceptive processing and pain perception. Earlier,
      experimental pain models often only involved induction of cutaneous pain using a
      single stimulus modality. Recently new experimental models have been developed
      eliciting various modalities of deep and visceral pain which more closely
      resemble clinical pain conditions. It is imperative to use multi-modal and multi
      structure pain induction and assessment techniques, because a simple model cannot
      describe the very complex and multi-factorial aspects of clinical pain.
      Furthermore, it is important to assess pain under normal and pathophysiological
      conditions. The importance of peripheral and central hyperexcitability for acute
      and chronic pain has been demonstrated in animals and, to some extent, in humans.
      However, in spite of our immense knowledge, we still do not know how to prevent
      and treat this hyperexcitability efficiently. Our understanding of nociceptive
      mechanisms involved in acute and chronic pain and the effects of anaesthetic
      drugs or combinations of drugs on these mechanisms in humans may also be expanded
      using human experimental models. This mechanism-based approach may help us to
      develop and test therapeutic regimes in patients with acute and chronic pain.

PMID- 12516898
TI  - Autosomal recessive catecholamine-induced polymorphic ventricular tachycardia.

PMID- 12516899
TI  - Excision of pterygium and conjunctival autograft.
AB  - BACKGROUND: Pterygium is a common disease in Israel. Different surgical
      techniques are used to manage it with varying degrees of success. OBJECTIVES: To
      evaluate the efficacy and safety of a conjunctival autograft after excision of
      pterygium. METHODS: Excision followed by conjunctival autograft was used to treat
      40 eyes of 40 patients with pterygium. The surgical results were evaluated
      retrospectively. Follow-up continued for a median of 296 days (range 6-1,056); 26
      cases were followed for more than 100 days (average 418 days) and comprised the
      study cohort. All reported procedures were performed consequentially and by one
      surgeon in the Tel Aviv Sourasky Medical Center, Israel between 1 June 1997 and
      31 March 2000. RESULTS: There were two recurrences of pterygium (2/26, 7.7%) 2
      months postoperatively. There were no major complications. Superficial comeal
      vessels (without concurrent fibrosis) appeared in 10 of 17 cases sutured with
      nylon, but none occurred in any of the seven grafts sutured with vicryl (P =
      0.068). The average LogMAR-corrected visual acuity of the study group improved
      slightly, from 6/16.5 to 6/11 (P = 0.003). CONCLUSIONS: Excision of pterygium
      with a conjunctival autograft is a safe and effective operation, with no
      procedure-specific added surgical risks. The relatively long surgical time and
      microsurgical methods required to perform the procedure properly have hindered
      its acceptance as the mainstream approach to pterygium management. Long-term
      follow-up is needed for better discernment of the surgical results in Israel.

PMID- 12516900
TI  - True primary Sjogren's syndrome in a subset of patients with hepatitis C
      infection: a model linking chronic infection to chronic sialadenitis.
AB  - BACKGROUND: Hepatis C virus infection is presently an exclusion criterion to
      classify Sjogren's syndrome; however, there are distinct clinicopathologic and
      biologic similarities between HCV-related and SS-related chronic inflammation of
      mucosa-associated lymphoid tissue and lymphoproliferation that suggest common
      pathogenetic pathways. OBJECTIVES: To determine whether a subset of patients with
      sicca syndrome and HCV infection may present a true primary SS rather than a
      distinct clinicobiologic entity. METHODS: We extensively characterized 20
      consecutive patients with positive anti-HCV antibodies and heavy subjective dry
      eye and/or dry mouth symptoms, plus positive unstimulated sialometry and/or
      Shirmer's test. We then compared these features with those in HCV-negative
      primary SS controls (classified according to the latest American-European
      Consensus Group Classification Criteria for SS). RESULTS: Of the 20 HCV-positive
      patients with sicca manifestations, 12 (60%) had positive anti-SSA/SSB antibodies
      (3/12 by enzyme-linked immunosorbent assay and 6/12 by immunoblot) and/or
      positive salivary gland biopsy (at least 1 focus/4 mm2), which met the strict
      classification criteria for SS, as in the case of HCV-negative SS controls.
      Comparing the HCV-positive SS subset with HCV-negative SS controls showed similar
      female to male ratio (11/1 vs. 46/4), major salivary gland swelling (17% vs.
      26%), positive antinuclear antibodies (75 vs. 94%) and positive rheumatoid factor
      (58 vs. 52%). Significant differences (P < 0.05) were seen in mean age (69 vs. 56
      years), liver disease (50 vs. 2%), lung disease (25 vs. 0%), anti-SSA/SSB
      positivity (25 vs. 90%), and low C3 or C4 (83 vs. 36%). HCV-positive SS patients
      exhibited a trend for more frequent chronic gastritis (50 vs. 22%), fibromyalgia
      (33 vs. 14%), peripheral neuropathy (33 vs. 18%), purpura (33 vs. 19%) and
      cryoglobulinemia (33 vs. 6%). CONCLUSIONS: A major subset of HCV-positive
      patients with definite subjective sicca symptoms and positive objective tests may
      indeed present a true, though peculiar, subset of SS. There are strict
      similarities with key clinical, pathologic and immunologic findings of definite
      HCV-negative SS. Other features appear more characteristic of HCV infection. When
      also considering that HCV is sialotropic and may be treated, HCV-related chronic
      sialadenitis represents a unique opportunity to clarify key pathogenetic events
      occurring in the large majority of HCV-negative SS; and similarities to typical
      primary SS, rather than differences, should be taken into account.

PMID- 12516901
TI  - Minimally invasive techniques in the treatment of liver tumors.
AB  - BACKGROUND: Despite advances in cancer therapy the treatment of liver tumors
      remains a challenge. Most patients are poor candidates for surgical resection;
      both chemotherapy and irradiation have a low success rate and neither is without
      complications. New minimally invasive techniques for ablation of unresectable
      tumors have gained attention as effective treatment alternatives. Among these are
      percutaneous ethanol injection and radiofrequency ablation; both are effective
      for primary liver tumors and RFA is also effective for hepatic metastases.
      OBJECTIVE: To report our experience with PEI and RFA in the treatment of hepatic
      lesions. METHODS: The study included 49 lesions in 27 patients: 23 primary
      lesions in 13 patents treated with PEI and 26 lesions (22 secondary and 4
      primary) in 14 patients treated with RFA. PEI was performed on an outpatient
      basis in the ultrasound suite; RFA was done in hospitalized patents (9 in the
      ultrasound suite and 4 in the operating room). Patients were followed with
      triphasic spiral computerized tomography 1 month after treatment and every 3-6
      months thereafter. RESULTS: Complete necrosis was achieved with PEI on the first
      attempt in 11 of 23 primary lesions (91.3%). In 8.7% (2/23) a second series of
      treatments was required. Using RFA, complete necrosis was achieved in 85% of
      lesions (22/26) and partial necrosis in 15% (4/26). Complications included low
      fever (3 patients), high fever and abscess formation (1 patient), peri-tumoral
      necrosis (1 patient) and portal vein thrombosis (1 patient). CONCLUSIONS: Our
      preliminary results confirm that PEI and RFA are an effective and safe option for
      treating hepatic tumors in patients unfit for surgery.

PMID- 12516902
TI  - Surveillance of neural tube defects in Israel.
AB  - BACKGROUND: Open neural tube defects are among the most common malformations of
      the fetus. Secondary prevention by early diagnosis during pregnancy and abortion
      of affected fetuses result in a marked reduction of NTD incidence at birth. The
      dramatic effect of folic acid for primary prevention of these defects led to
      recommendations for folic acid supplementation in women of reproductive age.
      OBJECTIVE: To describe the epidemiologic features of NTD in Israel in 1999-2000.
      METHODS: A national registry of NTD was begun in 1999. During the years 1999
      2000, a non-syndromic NTD was diagnosed in at least 394 pregnancies (166
      anencephaly, 166 spina bifida, 43 encephalocele, and 19 with other types of NTD).
      The religious-ethnic affiliation was known in 392 cases (209 Jews and 183 non
      Jews). RESULTS: Despite a marked decline in the rate of NTD at birth in the last
      few decades, the total rates during pregnancy did not change significantly,
      demonstrating that the changes were secondary to termination of affected
      pregnancies. At birth, NTD were almost four times more frequent among non-Jews
      (3.6 per 10,000 live births for anencephaly and 5.9 for spina bifida) than among
      Jews (anencephaly 1/10,000 live births, spina bifida 1.4/10,000 live births). The
      complete data of the registry showed an approximately twofold difference in the
      overall rates during pregnancy between Jews (anencephaly 5.3, spina bifida 4.6,
      total 11/10,000 live births) and non-Jews (anencephaly 8.8, spina bifida 10.3,
      total 22.3/10,000 live births). The registry demonstrated that the significant
      differences in NTD incidence observed at birth between Jews and non-Jews are
      secondary to a combined effect of a higher frequency of the malformations among
      non-Jews and a lower proportion of termination of affected pregnancies among non
      Jews. CONCLUSIONS: The data presented here will serve as a basis for evaluating
      the impact of the Ministry of Health recommendations for folic acid
      supplementation on the incidence of NTD.

PMID- 12516903
TI  - Epidemiologic risk factors for preterm delivery.
AB  - BACKGROUND: Prematurity remains the most significant cause of neonatal morbidity
      and mortality. Knowing which group of women is at risk for developing preterm
      labor will define a target population for better prenatal care and prevention
      modalities. OBJECTIVE: To examine whether preterm delivery rates are associated
      with ethnicity, age, parity, and style of living. METHODS: We conducted a
      longitudinal case series examining obstetric and demographic data of 17,493
      deliveries that occurred between June 1994 and May 1999. All deliveries were
      performed in the obstetric department of HaEmek Medical Center (Afula, Israel),
      which serves as a referral center. The main outcome measures were preterm
      delivery, as related to the women's ethnicity, age parity, and style of living-
      namely, town, village, or kibbutz. RESULTS: The overall preterm delivery rate was
      8.5%. The preterm delivery rate in non-Jewish women (10.5%) was higher than in
      Jewish women (7.1%) (P < 0.00001). The preterm delivery rate in women younger
      than 20 or older than 40 (12.5%) was much higher than in women between the ages
      of 21 and 40 (8.0%) (P < 0.00001). Grand-multipara women (> 8) had a higher
      preterm delivery rate (13.8%) than less parous women (8.5%) (P < 0.012). Style of
      living was also associated with the preterm delivery rate (P < 0.00001): kibbutz
      5.5%, Jewish towns 7.8%, non-Jewish towns 8.7%, Jewish villages 6.7%, and non
      Jewish villages 11.0%. CONCLUSIONS: Style of living, ethnicity, age and parity
      are statistically significant risk factors for preterm delivery in our area.
      These factors provide a more definable target population for better prenatal
      care.

PMID- 12516904
TI  - Cigarette smoking and hearing loss: lessons from the young adult periodic
      examinations in Israel (YAPEIS) database.
AB  - BACKGROUND: Some studies have indicated a possible link between cigarette smoking
      and hearing loss. OBJECTIVES: To analyze the association between smoking and
      hearing loss, other than that induced by noise, and to characterize the type of
      HL impairment found in smokers. METHODS: We conducted a retrospective cross
      sectional study in 13,308 men aged 20-68 (median 34.6 years) who underwent a
      hearing test as part of a routine periodic examination. For each subject, age,
      smoking status (current, past or non-smokers) and number of cigarettes per day
      were noted and a hearing test was performed. The test was performed in a sealed,
      soundproof room by an experienced audiologist and included pure tone audiometry
      of 250-8,000 Hz. The audiograms were analyzed and subjects were accordingly
      divided into two groups: those with HL and at least one of the following
      impairments in at least one ear: sensorineural, conductive or mixed; and those
      with no hearing loss (control). Audiograms showing HL typical to noise exposure
      were excluded. RESULTS: The prevalence of any type of HL among subjects < 35
      years was 4.5%, compared to 10.5% among those > 35 years (P < 0.0001). A
      significantly higher incidence of any type of HL was found in current (11.8%) and
      past smokers (11.7%) than in non-smokers (8.1%) (P < 0.0001). The risk increment
      of the smoking status for developing HL among subjects under age 35 was 43%, and
      17% among those above 35 years. Both mild, flat, sensorineural impairment and
      conductive impairment were found to be associated particularly with smoking (odds
      ratio 2.2 and 1.9, respectively). CONCLUSIONS: The incidence of HL unrelated to
      noise exposure is higher in smokers than in non-smokers, and in young adults the
      effect is greater.

PMID- 12516905
TI  - Familial multiple lipomatosis.
AB  - BACKGROUND: Familial multiple lipomatosis is an extremely rare disease. The
      disease usually does not affect the daily life of FML victims, but they may
      experience difficulty in performing everyday physical tasks if the lipomas are
      multiple and large. Inheritance is frequently by autosomal dominant transmission,
      although cases with recessive inheritance have also been reported. OBJECTIVES: To
      determine the pattern of inheritance of the disease in a family with 83 members
      spanning three generations. METHODS: A complete family analysis was performed and
      all surviving members of the family were examined. Laboratory investigations were
      conducted in those with FML, including serum lipid, cholesterol and glucose
      levels, white blood cell count, hemoglobin, erythrocyte sedimentation rate, and
      renal and hepatic function tests. RESULTS: There were no consanguineous
      relationships between spouses in the family. The disease was first seen on the
      neck of the (male) index patient. This patient had 4 sons, 8 daughters and 60
      grandchildren. The disease was established in four of his daughters and two of
      his sons. One of the female grandchildren whose mother has the disease was also
      affected. The laboratory findings were normal for all patients. CONCLUSION: Our
      findings showed that a) the disease is transmitted by the autosomal dominant
      route of inheritance; and b) lipomas observed at an early age may be numerous and
      large, may diffuse, and sometimes have to be excised surgically.

PMID- 12516906
TI  - New drugs for the treatment of cancer, 1990-2001.
AB  - Between 1990 and 2001, altogether 28 new anticancer drugs were approved for use
      in Israel. The new agents include cytotoxic drugs, biologic compounds, and
      hormone therapies. Among the cytotoxic agents introduced, the taxanes,
      vinorelbine, gemcitabine, irinotecan, topotecan and temozolomide, represent
      important new drugs active in a range of solid malignancies including lung,
      breast, ovarian, bladder, pancreatic, and colon cancer as well as brain tumors.
      Epirubicin, idarubicin, and liposomal doxorubicin offer less toxic and in some
      instances more effective alternatives to older anthracylines for leukemia, breast
      cancer, ovarian cancer and other diseases. New oral agents are offering a chance
      for disease palliation without the need for burdensome intravenous access.
      Rituximab and trastuzumab have introduced monoclonal antibody therapy to the
      clinic, substantially improving the treatment of patients with lymphoma and
      breast cancer, respectively. The first tyrosine kinase inhibitor, a molecularly
      targeted therapy, imatinib, was approved for use in chronic myeloid leukemia and
      has also shown remarkable activity in gastrointestinal stromal tumors. A variety
      of aromatase inhibitors have provided less toxic and more effective hormone
      therapy for the treatment of breast cancer. The challenge for clinicians is to
      optimize the use of the new available agents for their patients' benefit, and the
      challenge for health policy-makers in Israel is to integrate the new anticancer
      pharmaceuticals into the basic health benefits package mandated for all citizens.

PMID- 12516907
TI  - Legalizing the sale of kidneys for transplantation: suggested guidelines.

PMID- 12516908
TI  - Selective mutism: a review of the concept and treatment.

PMID- 12516909
TI  - Surgical management of pterygium.

PMID- 12516910
TI  - Compensation for kidney donation: a price worth paying.

PMID- 12516911
TI  - Sclerosing cholangitis--primary, secondary and more...

PMID- 12516912
TI  - Pulmonary vasculitis: a clinical overview.

PMID- 12516913
TI  - Villous adenoma of the common bile duct transforming into a cholangiocarcinoma.

PMID- 12516914
TI  - Bilateral renal abscesses in a healthy child.

PMID- 12516915
TI  - Caustic sclerosing cholangitis treated with orthotopic liver transplantation.

PMID- 12516916
TI  - Reversible mental and behavioral disturbances due to giant mediastinal
      parathyroid adenoma-induced hypercalcemia.

PMID- 12516917
TI  - A permanent tube-free tracheostomy in a morbidly obese patient with severe
      obstructive sleep apnea syndrome.

PMID- 12516918
TI  - Puzzling fever and neutropenia in a patient with Crohn's disease post-coronary
      artery bypass surgery.

PMID- 12516919
TI  - Bilateral coronary artery-pulmonary fistulae.

PMID- 12516920
TI  - Second Euroconference on Animal Models of Human Diseases.

PMID- 12516921
TI  - Quick detection of malaria.

PMID- 12516922
TI  - More about isosulfan blue.

PMID- 12516923
TI  - An off-duty doctor in the face of terrorism.

PMID- 12516924
TI  - Demographics of health and disease in the geriatric horse.
AB  - Owners of older horses have generally owned them for a long time. They have
      developed a bond that is similar to that seen with companion animals. Their
      desire to have their animal(s) age gracefully with comfort and mobility has
      stirred research in the field of equine geriatric medicine. Equine geriatric
      medicine is to the first decade of the twenty-first century as neonatal medicine
      was to the 1980s. Hopefully, the demographics discussed in this article highlight
      area where research can be most helpful.

PMID- 12516925
TI  - Anesthetic considerations of the older equine.
AB  - This article briefly reviews physiologic changes that may occur with aging in
      equine patients. It summarizes anesthetic protocols and problems encountered in a
      group of older horses (> 20 years old) anesthetized over the previous 10 years in
      the teaching hospital and makes recommendations for appropriate management of
      these patients.

PMID- 12516926
TI  - Managing chronic arthritis.
AB  - Many compounds are being investigated for the control of symptoms of
      osteoarthritis in people and animals. Ideally, treatment should include
      analgesia, inflammation control, and chondroprotection. With further progress in
      this area, combination therapies tailored to the needs of the individual animal
      should enable us to maximize efficacy and minimize side effects. Only a few of
      the newer therapies and pharmaceutic agents have been investigated in the horse,
      however. With more rigorous investigation, they may be determined to be
      ineffective or unsafe. Meanwhile, as much information should be gathered from
      manufacturers as possible so as to ensure that appropriate recommendations are
      made.

PMID- 12516927
TI  - Laminitis in the geriatric horse.
AB  - There are few diseases that instill a comparable sense of doom in the mind of a
      treating veterinarian as laminitis. There is a feeling of cautious optimism when
      a horse with laminitis responds favorably to treatment. Although this optimism
      all too often proves false when treating laminitic patients, management of the
      patient afflicted with chronic laminitis can be rewarding. Through diligent and
      careful client communication and instruction, many geriatric patients with
      chronic laminitis can be maintained for years as comfortable companions, for
      light riding use, or as productive breeding animals.

PMID- 12516928
TI  - Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient
      management.
AB  - Recurrent airway obstruction is a condition that affects some older horses
      maintained in confinement. Clinical signs range from exercise intolerance with
      occasional cough to dyspnea at rest. Bronchoalveolar lavage cytology is
      characterized by neutrophilic leukocytosis (15%-85%) and is recommended for
      making the diagnosis in horses with mild to moderate disease. Environmental
      management combined with periodic bronchodilator and antiinflammatory
      corticosteroid therapy yields the best prognosis for disease remission.

PMID- 12516929
TI  - Exercise physiology of the older horse.
AB  - Surveys indicate that up to 15% of the equine population in the United States is
      older than 20 years of age, with many of these animals performing various
      athletic activities well into their 20s. As is the case with their human
      counterparts, these geriatric equine athletes have the ability to continue to
      perform in athletic events. Unfortunately, many horse owners continue to train
      their active older animals using exercise training protocols that, although
      appropriate for a younger animal, may not be appropriate for the older equine
      athlete. Studies in aged human beings have led to a fine-tuning of exercise
      prescription for the older human athlete so as to prevent the adverse and
      potentially dangerous effects of excessive work. Published results have led to
      new and improved programs to promote fitness for the growing population of older
      adults. Unfortunately, limited data exist regarding the exercise capacity of the
      aged horse. Future studies on the effects of aging on exercise capacity in equine
      athletes need to take a few major directions. One question to be answered is at
      what age does physiologic function first begin to decline in the horse? In human
      beings, this age varies with training, but noticeable changes in aerobic capacity
      are first seen in 40- to 50-year-olds. Second, data are needed to determine what
      levels of exercise enhance the health and well-being of the older horse without
      harm. Lastly, studies are needed to determine the physiologic mechanisms
      associated with the onset of aging-induced decreases in physiologic function in
      the horse. The ultimate goal of all these studies should be to adjust exercise
      levels to meet the needs of the growing population of athletically active older
      equine athletes.

PMID- 12516930
TI  - Nutrition and feeding of the geriatric horse.
AB  - Little is known regarding nutrient requirements and feeding of geriatric horses,
      and more effort should be placed on this area of equine nutrition research. That
      which is known suggests that some geriatric horses may not have different
      requirements than other mature horses, whereas others affected by disease or poor
      dentition may have special nutritional needs. In general, rations for geriatric
      horses should be based on high-quality roughage supplemented with complementary
      minerals and vitamins. The need for additional energy aside from that provided by
      the forage can be supplied by adding energy concentrates, such as cereal grains
      or fat, to the ration. Processing techniques involving heat, such as pelleting
      and extruding, are advised when cereal grains are included in the ration so as to
      improve starch digestibility in the small intestine and avoid starch overload in
      the hindgut and it subsequent problem (ie, colic, laminitis). In addition, the
      environment in which geriatric horses are fed should be one that promotes ease of
      ration consumption and eliminates factors thar impair feed consumption, such as
      competition from other horses and the need to travel relatively long distances
      (eg, grazing marginal pastures). Finally, strict attention should be paid to the
      body condition of geriatric horses so as to evaluate adequacy of the ration and
      the general health of the horse.

PMID- 12516931
TI  - Dental care in the older horse.
AB  - Dental care in any horse need not be looked at as the difficult challenge it used
      to be before the days of sedation and tungsten carbide and diamond cutting
      wheels. Horses are living longer and more comfortable lives thanks, in part, to
      the advancements of dental care and special dietary rations. With the evolution
      of the horse's place in family circles today, people want the best care possible
      for their animals. Dentistry has become an important part of that care.

PMID- 12516932
TI  - Diagnostic workup for weight loss in the geriatric horse.
AB  - In the absence of debilitating medical problems, the geriatric horse can maintain
      a normal body condition when provided with an appropriate diet, adequate shelter,
      and preventive health care that includes regular dental care and deworming.
      Failures in management can lead to inadequate nutritional support, exposure to
      adverse environmental conditions, advanced dental disease, parasitism, and
      failure to detect developing medical problems. All these circumstances can lead
      to loss of condition and debilitation in the aged horse. Weight loss in the aged
      horse should be approached with an understanding of the basic pathophysiologic
      mechanisms of weight loss and the factors that can predispose older horses to
      weight loss. As always, a thorough history and physical examination are critical
      in reaching a diagnosis.

PMID- 12516933
TI  - Equine Cushing's disease.
AB  - Equine Cushing's disease (ECD) is a chronic progressive disease of the
      intermediate pituitary gland of older horses. Horses with Cushing's disease often
      have other health problems, such as laminitis, chronic infections,
      pseudolactation, and other issues. Diagnosis of ECD is usually based on clinical
      signs and endocrine tests. Medical management of affected horses is usually a
      long-term or lifelong commitment. The goal of this article is to review the
      pathophysiology of ECD, outline diagnostic tests, and present treatment options.

PMID- 12516934
TI  - Ophthalmic findings in the geriatric horse.
AB  - Ophthalmic conditions of the older horse are becoming increasingly common as
      geriatric care advances. The close relation between the eye and other structures
      of the head exposes the globe to direct expansion of clinical disease and raises
      management issues. Integrating an ophthalmic and fundic examination into the
      annual evaluation should reward the investment, permit enhanced patient care, and
      potentially provide early identification of systemic conditions. Surgical and
      medical management of neoplastic conditions is most successful with early
      identification and therapy. It is hoped that this article prompts the further
      identification and description of ophthalmic conditions as equine geriatric care
      increases in importance.

PMID- 12516935
TI  - Cardiac disease in the geriatric horse.
AB  - Almost all equine cardiac diseases may affect the geriatric horse. This article
      focuses on those cardiac diseases that are most common in the older horse,
      including degenerative valve disease, aortocardiac fistula, and congestive heart
      failure. Other cardiac diseases, such as bacterial endocarditis, pericarditis,
      and arrhythmias, are seen in all age groups of horses and are beyond the scope of
      this article.

PMID- 12516936
TI  - Reproductive considerations: mare and stallion.
AB  - Functional alterations within the reproductive system and in other supporting
      systems may limit the reproductive capacity of geriatric patients; however, the
      age of onset and degree of compromise show wide individual variation. Aging of
      the hypothalamopituitary-ovarian axis in the mare manifests as delayed entry to
      the breeding season, prolonged follicular phases, reduced response to ovulation
      induction, irregular cycles, oocyte defects, increased early embryonic death,
      and, eventually, persistent anestrus. Aging of the reproductive tract may
      increase her susceptibility to endometritis, compromise placental formation with
      long-term effects on the fetus and viability of the resulting foal, increase her
      risk of ascending placentitis, alter gestation length, and make her more prone to
      catastrophic rupture of the uterine arteries at the time of parturition. Effects
      on the stallion are less well documented but include a reduction in sperm output
      associated with progressive testicular degeneration and potential compromise of
      libido and mating ability that is often associated with degenerative conditions
      of the musculoskeletal system.

PMID- 12516937
TI  - The effect of aging on immune responses.
AB  - Although vaccine manufacturers make no specific recommendations regarding the
      vaccination of older horses and ponies, the similarities in age-induced
      immunologic changes between human beings and equids suggests that similar
      vaccination recommendations should be followed. The need for vaccination of the
      older horse depends, of course, on the relative risk of exposure for the
      individual horse. Particular care should be taken when using attenuated vaccine
      products because these live agents may pose a unique risk to the older
      individual. Immunization with inactivated agent vaccines is likely to be safer.
      In general, annual vaccination against equine influenza virus infection, tetanus,
      rabies, and encephalomyelitis viruses is warranted.

PMID- 12516938
TI  - Use of complementary veterinary medicine in the geriatric horse.
AB  - The use of complementary and alternative veterinary medicine continues to grow
      within the veterinary community. As more clients seek out complementary and
      alternative medicine for their own health care, they begin to seek out these
      forms of therapy for their animals. For the equine practitioner, this includes
      those clients with geriatric animals. It is hoped that this article provides some
      insight into what conditions may be helped with CVM (complementary veterinary
      medicine) and when an equine practitioner may want to consider CVM as a form of
      therapy for the geriatric horse.

PMID- 12516939
TI  - Pharmacokinetics and safety of valaciclovir in children with Epstein-Barr virus
      illness.
AB  - OBJECTIVE: Valaciclovir has in vitro activity against Epstein-Barr virus (EBV)
      and, because of improved absorption with higher achievable serum concentrations,
      may be more effective than aciclovir in the treatment of EBV. No studies to date
      have evaluated the efficacy, safety or proper dosing of valaciclovir in children
      for the treatment of EBV infection. The objectives of this study were to
      determine the pharmacokinetics and safety of valaciclovir tablets and suspension
      in children with EBV illness. METHODS: 24 children with EBV illness were
      randomised to receive valaciclovir suspension 10 mg/kg or 20 mg/kg; eight
      children subsequently were crossed over and also received valaciclovir 500 mg
      tablets. Doses of either suspension or tablets were administered every 8 hours
      for four doses, and pharmacokinetic studies were performed to determine aciclovir
      serum concentrations. Samples for drug assay were obtained at 0, 0.5, 1, 2, 4, 6,
      8 and 24 hours. Samples were assayed by high performance liquid chromatography
      (HPLC) methods and aciclovir pharmacokinetics determined using non-compartmental
      analysis. RESULTS: Valaciclovir pharmacokinetic parameters (mean +/- SD) in
      children who received tablets and suspension (normalised to 500 mg dose) were:
      maximum serum concentration (C(max)) 3.16 +/- 1.30 and 2.42 +/- 0.74 mg/L, time
      to maximum serum concentration (t(max)) 1.88 +/- 0.99 and 1.31 +/- 0.53 hours,
      half-life (t 1/2) 1.72 +/- 0.41 and 1.94 +/- 0.60 hours, apparent total systemic
      clearance (CL/F) 20.01 +/- 6.61 and 15.58 +/- 3.34 ml/min/kg, volume of
      distribution/bioavailability (Vd/F) 3.04 +/- 1.26 and 2.58 +/- 0.81 L/kg, and
      area under the concentration-time curve (AUC) 10.13 +/- 3.47 and 8.59 +/- 2.52 mg
      x h/L, respectively. There were no statistically significant differences in the
      pharmacokinetics of valaciclovir tablets versus suspension. The relative
      bioavailability of the valaciclovir tablets compared with the suspension was 115
      +/- 32%. Valaciclovir was well tolerated, with gastrointestinal disturbances and
      headache being the most common adverse effects in a small number of subjects.
      CONCLUSIONS: Valaciclovir is absorbed and achieves concentrations in children
      that appear to be effective for the treatment of herpes lesions. The
      pharmacokinetics of valaciclovir suspension and tablets are similar, and the
      pharmacokinetics of aciclovir after administration of valaciclovir to children
      are similar to historical observations of aciclovir pharmacokinetics in adults.
      Valaciclovir has a good safety profile and was well tolerated after oral
      administration in this group of children.

PMID- 12516940
TI  - Six-month toxicity study of oral administration of D-003 in Sprague Dawley rats.
AB  - BACKGROUND: D-003 is a mixture of high molecular weight aliphatic primary acids
      purified from sugarcane wax (Saccharum officinarum) having cholesterol-lowering
      and antiplatelet effects. AIM: This study was undertaken to investigate the
      toxicity induced by long-term oral administration of D-003 for 6 months to
      Sprague Dawley rats of both sexes. METHODS: Rats were randomly divided into four
      groups (20 rats of each sex/group): a control group. which received the vehicle,
      and three treatment groups, which received oral D-003 at doses of 250, 500 and
      1000 mg/kg/day, respectively. Daily clinical observations and control of
      bodyweight and food consumption were conducted throughout the study period. On
      completion of active treatment, animals were sacrificed. Pharmacological effects
      associated with D-003 such as inhibition of platelet aggregation and increase in
      bleeding time were assessed in two satellite groups (14 animals of each
      sex/group): a control group and a group treated with the highest dose of D-003.
      Assessments of platelet aggregation to collagen were performed at baseline and at
      6 months, and assessments of bleeding time were done at baseline, after 3 and 6
      months of treatment, and after 30 days' washout. RESULTS: As expected, D-003
      significantly inhibited platelet aggregation. Bleeding time was increased after 3
      months of treatment with D-003; this increase was maintained at 6 months, and was
      reversible after washout. Coagulation factors such as prothrombin time and kaolin
      activated thromboplastin-time, which were determined in eight male animals from
      each group, were unaffected by D-003. Data analyses of bodyweight gain, food
      consumption, clinical observations, blood biochemistry, haematology, organ weight
      ratios and histopathological findings did not show trends related to D-003 dose
      or significant differences between control and treated groups. CONCLUSION: It was
      concluded that the highest studied dose of D-003 (1,000 mg/kg/day) represented a
      non-toxic dose level in the present chronic toxicity study in rats.

PMID- 12516942
TI  - Levonorgestrel--Gedeon Richter. Levonelle-2, Plan B, Postinor, Postinor-2.

PMID- 12516941
TI  - Users' perspectives on bleeding patterns after two years of levonorgestrel
      releasing intrauterine system use.

PMID- 12516943
TI  - Levonorgestrel1--Leiras Oy. Levonova, Mirena.

PMID- 12516944
TI  - Levonorgestrel--implant. Jadelle, Norplant-2.

PMID- 12516945
TI  - Bismuth subcitrate/metronidazole/ tetracycline--Axcan Pharma. Bismuth triple
      therapy--Axcan Pharma, Helicide.

PMID- 12516946
TI  - Blonanserin. AD 5423.

PMID- 12516947
TI  - Ciclesonide. BY 9010, ciclesonide-DPI, ciclesonide-MDI, EL 876.

PMID- 12516948
TI  - HIV vaccine--immune response. AG 1661, IR-8101, IR8101, REMUNE, RG 83894.

PMID- 12516949
TI  - Melagatran. Exanta, H 319/68.

PMID- 12516950
TI  - Prulifloxacin. NAD-441A, NM 441, Quisnon.

PMID- 12516951
TI  - Ximelagatran. Exanta, H 376, H 376/95, H 37695.

PMID- 12516953
TI  - Immune-mediated inflammatory disorders (I.M.I.D.s): the economic and clinical
      costs.
AB  - Immune-mediated inflammatory disorders (I.M.I.D.s) are a group of diseases that
      involve an immune response that is inappropriate or excessive, and is caused,
      signified, or accompanied by dysregulation of the body's normal cytokine milieu.
      I.M.I.D.s cause acute or chronic inflammatory injury, sometimes severe, in any
      organ system. Despite strong evidence linking the pathophysiologies and
      treatments of the diseases that constitute the I.M.I.D. group, providers, payers,
      employers, and benefits consultants have been slow to adopt the I.M.I.D. concept.
      As a result, these stakeholders risk underestimating the significant clinical and
      economic burdens of the I.M.I.D. class. In this review we examine those burdens,
      specifically analyzing I.M.I.D. prevalence and cost data for a group of large
      employers. We also describe the scientific rationale for the I.M.I.D. paradigm,
      examine the cytokine dysregulation that many I.M.I.D.s share, and focus in detail
      on the pathophysiology of 3 I.M.I.D.s with high morbidity: rheumatoid arthritis,
      Crohn's disease, and type 1 diabetes mellitus. The review concludes with an
      evaluation of approved anticytokine I.M.I.D. therapies and those in development.

PMID- 12516954
TI  - Health-related consequences of overactive bladder.
AB  - OBJECTIVE: Overactive bladder (OAB) is a condition of urgency, with or without
      urge incontinence, usually with frequency and nocturia. This study assesses
      whether people with OAB are at greater risk for urinary tract infections (UTIs),
      falls and injuries, and increased number of visits to the doctor compared to age-
      and gender-matched controls. The study also estimates costs associated with these
      health-related consequences. PATIENTS & METHODS: A US representative telephone
      survey under the National Overactive Bladder Evaluation (NOBLE) Program was
      conducted with 5204 English-speaking adults older than 18 years. The survey asked
      respondents about bladder symptoms. Based on the telephone survey, 865 symptom
      identified OAB cases and 903 age- and gender-matched controls were sent a postal
      questionnaire. A total of 397 cases and 522 controls returned the questionnaires.
      Nonrespondent cases and controls did not differ with regard to age, gender,
      educational status, diabetes, congestive heart failure, and self-rated health
      status. Regression analyses were conducted to assess the effect of OAB on health
      related consequences, controlling for age, gender, race, education, marital
      status, number of previous births, self-reported health status, diabetes, and
      congestive heart failure. RESULTS: People with OAB reported 0.84 (20%) more
      visits to the physician (P < .05) and 0.21 (138%) more UTIs in the last year than
      people without OAB (P < .001). Overactive bladder cases also had over twice the
      odds of being injured in a fall than people without OAB (odds ratio = 2.26; 95%
      confidence interval 1.46, 3.51). Consistent with having more falls, OAB cases had
      an increased risk of bone fracture (P < .1). This effect, however, was not
      statistically significant (at alpha level 0.05) due to the limited sample size.
      The estimated cost of UTIs associated with OAB was approximately $1.37 billion US
      dollars in year 2000. The cost of falls without bone fracture due to OAB was $55
      million. Falls with bone fracture accounted for approximately $386 million;
      however, further research with a larger sample is needed to accurately estimate
      these costs. CONCLUSION: People with OAB self-report significantly more UTIs and
      a greater risk of being injured in a fall. Given the large prevalence of UTIs and
      concerns of overprescribing antibiotics, these results are important for health
      plans and policy makers. In addition, people with OAB visit their physicians more
      often than people without OAB. These consequences entail significant economic
      costs, of which a large percentage will be incurred by health plans. To the
      extent that OAB causes these consequences, there may be significant savings from
      effectively treating OAB.

PMID- 12516955
TI  - Health-related quality of life of patients receiving extended-release tolterodine
      for overactive bladder.
AB  - OBJECTIVE: To compare the health-related quality of life (HRQoL) of overactive
      bladder (OAB) patients foilowing treatment with tolterodine extended-release (ER)
      4 mg once daily versus placebo. STUDY DESIGN: Multinational, placebo-controlled,
      randomized, double-blind 12-week study. POPULATION: Patients with urinary
      frequency ( > or = 8 micturitions/24 hours over a 7-day period), urge
      incontinence ( > or = 5 episodes/week), and symptoms of OAB for at least 6 months
      were eligible for inclusion. Patients (81% female) received oral therapy with
      tolterodine ER (n = 507) or placebo (n = 508) for 12 weeks. OUTCOMES MEASURED:
      HRQoL was assessed using the King's Health Questionnaire (KHQ) and Medical
      Outcomes Study Short Form 36-item questionnaire (SF-36). Patients also rated
      their bladder condition. Assessments were performed at baseline and at the end of
      treatment. RESULTS: At end of treatment, KHQ domains selected a priori as primary
      HRQoL end points (incontinence impact and role limitations) significantly
      improved (P < or = .001) with tolterodine ER. Domains selected a priori as
      secondary end points (physical limitations, sleep and energy, severity [coping]
      measures, and symptom severity) were also significantly improved (P < or = .006)
      following treatment with tolterodine ER. The tolterodine ER group had decreased
      symptom severity and statistically significant improvements in patient rating of
      bladder control compared with the placebo group at end of treatment. No treatment
      differences were detected using the SF-36. CONCLUSION: Many aspects of HRQoL, as
      measured by the KHQ, showed statistically significant improvement following
      treatment with tolterodine ER. These HRQoL improvements were consistent with
      clinical efficacy benefits. Patients receiving tolterodine ER experienced overall
      improvement in their condition that was associated with an important impact on
      their HRQoL.

PMID- 12516956
TI  - Long-term health-related quality of life of patients receiving extended-release
      tolterodine for overactive bladder.
AB  - OBJECTIVE: To evaluate the long-term effects of tolterodine on the health-related
      quality of life (HRQoL) of patients diagnosed with overactive bladder with
      incontinence. METHODS: Patients who completed a 12-week randomized, double-blind,
      safety and efficacy trial comparing tolterodine with placebo were invited to
      enroll in a 12-month open-label continuation trial to assess the long-term safety
      and efficacy of tolterodine. This study reports the HRQoL results from the King's
      Health Questionnaire (KHQ) and the Short Form-36 (SF-36) that were administered
      at baseline, at the end of the 12-week trial, and 3 and 12 months following open
      label treatment with tolterodine. RESULTS: One thousand seventy-seven patients
      were included in the intent-to-treat (ITT(B)) population. KHQ translations were
      available for 838 patients (mean age, 61.1 years; 80.9% women) in the ITT(B)
      population. HRQoL, as measured by the KHQ, significantly improved from baseline
      to months 3 and 12 on the following domains: incontinence impact, role
      limitations, physical limitations, social limitations, personal relationships,
      emotions, sleep and energy, severity (coping) measures, and symptom severity.
      Improvements were generally consistent across all analyses for the 3- and 12
      month measurements and for the ITT(B) and completer (C(B)) populations. Patients
      receiving tolterodine in the double-blind study showed additional improvement at
      the 3-month open-label assessment on all but the general health domain. At 12
      months from treatment rollover, all improvements from rollover to 3 months were
      sustained with additional improvement seen on the incontinence impact and role
      limitations domains. The general health perceptions domain showed a slight
      decline from rollover that might be attributable to a natural decline in
      patients' health status at this life stage. These findings were consistent with
      other efficacy results whereby efficacy was maintained over the 12-month open
      label period. SF-36 results were consistent with previous experience of reduced
      sensitivity, as population groups were similar to the SF-36 Physical Component
      and Mental Component scores at various time points and with all populations.
      CONCLUSION: Continued treatment with tolterodine provides additional benefits in
      HRQoL as measured by the KHQ. Of particular importance are improvements on the
      psychological aspects after longer-term treatment not detected after a short-term
      trial. Treatment effects on HRQoL are evident even after a 12-week placebo run-in
      supporting the true clinical effect of active treatment.

PMID- 12516957
TI  - Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in
      orthotopic human pancreatic tumor xenografts.
AB  - Recent studies have shown that the transcription factor, nuclear factor kappaB
      (NF-kappaB), regulates critical survival pathways in a variety of different cell
      types, including human pancreatic cancer cells. The activation of NF-kappaB is
      controlled by proteasome-mediated degradation of its endogenous polypeptide
      inhibitor, inhibitor of nuclear factor kappaBalpha. We investigated the effects
      of PS-341, a peptide boronate inhibitor of the proteasome in human pancreatic
      cancer cells in vitro and in vivo. Comparison of PS-341's effects on the growth
      of eight different human pancreatic cancer cell lines revealed marked
      heterogeneity in drug responsiveness, ranging from highly resistant (IC50 > 10
      microM; Panc-48, HS766T, and Mia-PaCa-2) to extremely sensitive (IC50 < 40 nM;
      L3.6pl, Hpaf2, and BxPC3). However, these effects did not correlate with
      differential inhibition of NF-kappaB activation. Direct quantification of
      apoptosis revealed that PS-341's effects on cell growth largely correlated with
      sensitivity to programmed cell death. Evaluation of PS-341's effects on
      established orthotopic tumor xenografts demonstrated that biweekly intravenous
      administration of the maximum-tolerated dose of the drug (1 mg/kg) led to
      significant reductions in the volumes of L3.6pl tumors but not Mia-PaCa-2 tumors.
      Laser scanning cytometer-mediated quantification of drug-induced apoptosis in the
      xenografts confirmed that PS-341 induced DNA fragmentation and activation of
      caspase-3 in L3.6pl tumors but not in Mia-PaCa-2 tumors. However, histological
      examination of drug-treated tumors revealed extensive central necrosis and
      reductions in microvessel density and VEGF expression in both tumor types. Taken
      together, our results demonstrate that PS-341 inhibits the growth of human
      pancreatic tumors via direct effects on tumor cells and indirect effects on the
      tumor vasculature.

PMID- 12516958
TI  - Pentamidine is an inhibitor of PRL phosphatases with anticancer activity.
AB  - The PRL family oncogenic phosphatases are attractive targets for developing
      inhibitors as anticancer therapeutics given their potentially pathogenic role in
      human malignancies. Herein we demonstrate that pentamidine, an anti-protozoa drug
      with an unknown mechanism of action, is an inhibitor of PRLs with anticancer
      potential. Pentamidine at its therapeutic doses inhibited recombinant PRL
      phosphatases in vitro and inactivated ectopically expressed PRLs in NIH3T3
      transfectants with an effective duration more than 24 h after a pulse cell
      treatment. The drug had in vitro growth-inhibitory activity against human cancer
      cell lines that express the endogenous PRLs. Pentamidine at a tolerable dose
      markedly inhibited the growth of WM9 human melanoma tumors in nude mice
      coincident with the induction of tumor cell necrosis and is capable of
      inactivating ectopically expressed PRL-2 in the cancer cells. These observations
      suggest the potential of pentamidine in anticancer therapies and may provide a
      basis for developing novel PTPase-targeted therapeutics.

PMID- 12516959
TI  - Deregulated cyclooxygenase-2 expression in oral premalignant tissues.
AB  - Establishment of an early and reliable biomarker for oral carcinogenesis whose
      expression can be monitored through noninvasive techniques will enable early
      diagnosis of cancer. Cyclooxygenases (COXs) have been implicated previously in
      several human malignancies, and the therapeutic benefit of specific COX-2
      inhibitors has been elucidated. The expression of COX-2 and subsequent markers of
      malignant progression was studied in archival human specimens representing
      premalignant and malignant stages of oral cancer. We find that changes in COX-2
      gene expression precede changes in expression of biomarkers related to apoptosis
      and angiogenesis in oral premalignant tissues as a veritable phenotype. We also
      report for the first time COX-2 mRNA variants in dysplastic samples and in a
      human papillomavirus-transformed cell line HOK-16B, indicating a possible
      stabilization of COX-2 message by human papillomavirus infection as an early
      event in oral cancer. Expression of other markers of tumor progression related to
      apoptosis and angiogenesis pathway genes shows relatively low level of changes in
      oral premalignant tissue. However, a determinant shift toward decrease in
      antitumor immunity was observed by cytokine gene expression profile changes.

PMID- 12516960
TI  - Endothelin-2 is a hypoxia-induced autocrine survival factor for breast tumor
      cells.
AB  - Endothelins (ETs) are a group of vasoactive peptides (ET-1, ET-2 and ET-3)
      produced by many cell types that bind to G-protein-linked transmembrane
      receptors, ET-A receptors (ET-RAs) and ET-B receptors (ET-RBs). These peptides
      are expressed in several human tumors, including carcinomas of the breast, and
      have a mitogenic effect in ovarian cancer cell lines. We investigated ET
      expression in infiltrating ductal carcinomas (IDCs) of the breast and the
      relationship between ET and hypoxia. ET staining was increased in human grade II
      IDC samples compared with normal breast tissue. ET-2 and ET-RB mRNA expression
      were absent in the majority of normal human breast samples (1 of 5 and 0 of 5,
      respectively) but was present in the majority of IDC tested (13 of 15 and 12 of
      15, respectively). In a murine breast cancer model, HTH-K, ET-2, and ET-RB mRNA
      were detected in tumor but not normal breast tissue, and ET expression
      colocalized with areas of hypoxia. In vitro, ET-2, ET-RA, and ET-RB mRNA were
      increased by incubating HTH-K cells in hypoxia (0.1% oxygen) for 24 h. Hypoxia
      also up-regulated ET-2 mRNA in several human breast tumor cell lines. ET-2 mRNA
      increased within 3 h in a hypoxia-inducible factor 1-dependent manner. The ET-RB
      antagonist BQ-788 increased in hypoxia-associated apoptosis of breast tumor cells
      in vitro. These effects could be reversed by addition of ET-2 peptide.
      Intratumoral injection of BQ-788 led to an increase in the development and extent
      of necrosis within the HTH-K tumor and a decrease in the rate of tumor growth.
      The ET-RA antagonist, BQ-123, also led to a decrease in tumor growth but without
      a concomitant increase in necrosis. We propose that modulation of ET-2 production
      via the hypoxia-inducible factor 1 transcription factor and autocrine signaling
      via ET-RB is a novel mechanism by which tumor cells can withstand hypoxic stress.
      Treatment of breast carcinomas with ET receptor antagonists may have a
      therapeutic benefit.

PMID- 12516961
TI  - Multiple comparisons model-based clustering and ternary pattern tree numerical
      display of gene response to treatment: procedure and application to the
      preclinical evaluation of chemopreventive agents.
AB  - Microarray technology has greatly aided the identification of genes that are
      expressed differentially. Statistical analysis of such data by multiple
      comparisons procedures has been slow to develop, in part, because methods to
      cluster the results of such comparisons in biologically meaningful ways have not
      been available. We isolated and analyzed, by Northern blot and GeneChip,
      replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet
      containing one of three chemopreventive compounds, selected because their
      pharmacological activities, including RNA expression response, are relatively
      well understood. We report on a classification tree, based on the results of
      nonparametric multiple comparisons, which results in the bipolar hierarchical
      clustering of genes in relation to their response to treatment. In addition to
      identifying treatment-responsive genes, application of this procedure to our test
      study identified the known pharmacological relationships among the treatment
      groups without supervision. Also, small treatment-specific subsets of genes were
      identified that may be indicative of additional pharmacophores present in the
      test compounds.

PMID- 12516962
TI  - Multiplex gene expression analysis for high-throughput drug discovery: screening
      and analysis of compounds affecting genes overexpressed in cancer cells.
AB  - Drug discovery strategies are needed that can rapidly exploit multiple
      therapeutic targets associated with the complex gene expression changes that
      characterize a polygenic disease such as cancer. We report a new cell-based high
      throughput technology for screening chemical libraries against several potential
      cancer target genes in parallel. Multiplex gene expression (MGE) analysis
      provides direct and quantitative measurement of multiple endogenous mRNAs using a
      multiplexed detection system coupled to reverse transcription-PCR. A multiplex
      assay for six genes overexpressed in cancer cells was used to screen 9000
      chemicals and known drugs in the human prostate cancer cell line PC-3. Active
      compounds that modulated gene expression levels were identified, and IC50 values
      were determined for compounds that bind DNA, cell surface receptors, and
      components of intracellular signaling pathways. A class of steroids related to
      the cardiac glycosides was identified that potently inhibited the plasma membrane
      Na(+)K(+)-ATPase resulting in the inhibition of four of the prostate target genes
      including transcription factors Hoxb-13, hPSE/PDEF, hepatocyte nuclear factor
      3alpha, and the inhibitor of apoptosis, survivin. Representative compounds
      selectively induced apoptosis in PC-3 cells compared with the nonmetastatic cell
      line BPH-1. The multiplex assay distinguished potencies among structural
      variants, enabling structure-activity analysis suitable for chemical optimization
      studies. A second multiplex assay for five toxicological markers, Hsp70, Gadd153,
      Gadd45, O6-methylguanine-DNA methyltransferase, and cyclophilin, detected
      compounds that caused DNA damage and cellular stress and was a more sensitive and
      specific indicator of potential toxicity than measurement of cell viability. MGE
      analysis facilitates rapid drug screening and compound optimization, the
      simultaneous measurement of toxicological end points, and gene function analysis.

PMID- 12516963
TI  - Synthesis and high content cell-based profiling of simplified analogues of the
      microtubule stabilizer (+)-discodermolide.
AB  - (+)-Discodermolide, a C24:4, trihydroxylated, octamethyl, carbamate-bearing fatty
      acid lactone originally isolated from a Caribbean sponge, has proven to be the
      most potent of the microtubule-stabilizing agents. Recent studies suggest that it
      or its analogues may have advantages over other classes of microtubule
      stabilizing agents. (+)-Discodermolide's complex molecular architecture has made
      structure-activity relationship analysis in this class of compounds a formidable
      task. The goal of this study was to prepare simplified analogues of (+)
      discodermolide and to analyze their biological activities to expand structure
      activity relationships. A small library of analogues was prepared wherein the (+)
      discodermolide methyl groups at C-14 and C-16 and the C-7 hydroxyl were removed,
      and the lactone was replaced by simple esters. The library components were
      analyzed for microtubule-stabilizing actions in vitro, antiproliferative activity
      against a small panel of human carcinoma cells, and cell signaling, microtubule
      architecture and mitotic spindle alterations by a multiparameter fluorescence
      cell-based screening technique. The results show that even drastic structural
      simplification can lead to analogues with actions related to microtubule
      targeting and signal transduction, but that these subtle effects were illuminated
      only through the high information content cell-based screen.

PMID- 12516964
TI  - 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid (XK469) inhibition of
      topoisomerase IIbeta is not sufficient for therapeutic response in human
      Waldenstrom's macroglobulinemia xenograft model.
AB  - The role of DNA topoisomerase (Topo) IIbeta in cancer chemotherapy remains
      unclear, although this particular isoform has been implicated in drug resistance.
      In this study, we investigated Topo IIbeta as a target for 2-[4-(7-chloro-2
      quinoxalinyloxy)phenoxy]-propionic acid (XK469), a novel synthetic quinoxaline
      phenoxypropionic acid derivative, in a Waldenstrom's macroglobulinemia (WM)
      model. In vitro, the WSU-WM cell line was exposed to 1.0, 2.0, 5.0, 8.0, and 10
      microM XK469. Our results demonstrate a concentration-dependent cell growth
      inhibition with a concentration-independent inhibition of Topo IIbeta, as
      determined by band depletion assay. The cell growth inhibition of cells
      correlated well with increase in Bax:Bcl-2 ratio and poly(ADP-ribose) polymerase
      (PARP) cleavage. We used our established WSU-WM severe combined immunodeficient
      mouse xenograft model to test the efficacy and effect of XK469 on Topo IIbeta in
      vivo. Topo IIbeta was inhibited equally using two different dose schedules (20
      and 40 mg/kg, i.v., for a total of 120 and 240 mg/kg, respectively); however,
      there was no significant decrease in tumor weight. Western blot analysis of cells
      isolated from s.c. tumors showed no induction of the Bax protein and a very low
      Bax:Bcl-2 ratio of approximately 0.3 in correlation with minimum PARP cleavage.
      Our study shows that XK469 inhibits Topo IIbeta in WSU-WM cells both in vitro and
      in vivo at or below the maximum tolerated dose in severe combined immunodeficient
      mice. However, there was no change of apoptosis-related molecules such as PARP,
      Bax, and Bcl-2 or reduction in tumor weight in association with Topo IIbeta
      inhibition. We conclude that Topo IIbeta inhibition by XK469 as a target is not
      sufficient for therapeutic effects in WSU-WM.

PMID- 12516965
TI  - 2-[4-(7-chloro-2-quinoxalinyloxyphenoxy]-propionic acid (XK469), an inhibitor of
      topoisomerase (Topo) IIbeta, up-regulates Topo IIalpha and enhances Topo IIalpha
      mediated cytotoxicity.
AB  - Topoisomerase (Topo) IIalpha has proven to be an adequate anticancer target for
      tumors expressing this enzyme. In this study, we elucidated the effect of 2-[4-(7
      chloro-2-quinoxalinyloxyphenoxy]-propionic acid (XK469; a new Topo IIbeta
      inhibitor) in the modulation of Topo IIalpha levels and sensitivity to Topo
      IIalpha poisons. We demonstrate by Western blot analysis that indolent B-cell
      tumors express undetectable levels of this enzyme and are refractory to the
      effects of Topo IIalpha poisons such as VP16. Using the Waldenstrom's
      macroglobulinemia (WM) cell line WSU-WM, we show that XK469 induced the
      expression of Topo IIalpha protein by 24 h compared with control.
      Immunofluorescence studies by confocal microscopy using a specific monoclonal
      antibody against Topo IIalpha supported the immunoblot findings with high
      intensity staining in XK469-exposed cells. To determine the effect of up
      regulating Topo IIalpha on sensitivity of Topo IIalpha-directed inhibitors, WSU
      WM cells were exposed to simultaneous, sequential, and reverse order XK469 and
      VP16. We demonstrate that 24 h of exposure to XK469 before VP16 resulted in a
      maximum synergistic response. In contrast, simultaneous or reverse order exposure
      resulted in an antagonistic effect. A similar trend was observed with cells
      obtained from chronic lymphocytic leukemia patients, but not in normal
      lymphocytes. This increase in VP16 sensitivity after 24 h of XK469 exposure was
      associated with VP16-dependent DNA cleavage, as demonstrated by formation of a
      smeared DNA band in a SDS-KCL DNA cleavage assay. From this study, we concluded
      that XK469 up-regulates Topo IIalpha levels and consequently sensitizes indolent
      malignant B cells to the cytotoxic effect of VP16 in a schedule-dependent manner.

PMID- 12516966
TI  - Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell
      lines by ecteinascidin 743.
AB  - Ecteinascidin 743 (Et-743) is a novel anticancer agent forming covalent guanine
      adducts at specific sites in the DNA minor groove. Et-743 has a unique mechanism
      of action because it kills cancer cells by poisoning transcription-coupled
      nucleotide excision repair. Recent studies suggested a complex relationship
      between P-glycoprotein (P-gp)/MDR1 and Et-743. On one hand, Et-743 was reported
      to down-regulate the MDR1 promoter in vitro. On the other hand, P-gp
      overexpression was hypothesized to contribute to Et-743 resistance in an ovarian
      cell line. The present study was performed to further investigate the
      relationship between P-gp/MDR1 and the activity of Et-743. First, we found no P
      gp/MDR1 overexpression (mRNA and protein levels) in two independently generated
      Et-743-resistant human colon carcinoma cell lines (HCT116/ER5 and SW480/ER0.5).
      Secondly, we found no cross-resistance to Et-743 in two well-characterized P
      gp/MDR1-overexpressing cell lines (KB-8-5 and KB-C-2). Third, Et-743 pretreatment
      enhanced the cytotoxicity and the cellular accumulation of doxorubicin and
      vincristine in P-gp/MDR1-overexpressing KB-8-5/KB-C-2 cell lines. Fourth, we
      observed P-gp/MDR1 down-regulation by Et-743 in KB-C-2 cells. These results
      indicate that Et-743 does not select for the emergence of a P-gp phenotype in all
      cell lines made resistant to Et-743 and that P-gp overexpression is not
      sufficient to confer resistance to Et-743. Furthermore, Et-743 is an effective
      agent in P-gp-overexpressing cells. Et-743 can potentiate the activity of other
      chemotherapeutic agents by down-regulating P-gp/MDR1, suggesting that the
      combination of Et-743 and chemotherapeutic agents that are substrates for P
      gp/MDR1 may be valuable in the clinic.

PMID- 12516967
TI  - Identification and characterization of the canine multidrug resistance-associated
      protein.
AB  - Human multidrug resistance protein 1 (MRP1) confers resistance to the Vinca
      alkaloids, the anthracyclines, and the epipodophyllotoxins. It is also capable of
      binding to and transporting the glutathione S-conjugate leukotriene C4 (LTC4) in
      isolated membrane vesicles. To explore species differences that exist between MRP
      orthologs, we cloned and characterized the mRNA encoding a canine ortholog of
      human MRP1-designated canine MRP1 (canMRP1). The canMRP1 mRNA encodes a protein
      of identical length as MRP1. Sequence alignment revealed that canMRP1 was 92%
      identical to MRP1 and 88% identical to murine mrp1. Five polymorphisms were
      identified in the canMRP1 cDNA coding sequence, including one resulting in an
      amino acid change from alanine to serine at aa149 (canMRP1-A and B alleles,
      respectively). canMRP1 was expressed and functionally characterized in HeLa and
      A2780 cells. Both alleles conferred an increased resistance to vincristine and
      etoposide and transported LTC4. The compound LY402913, a modulating agent
      developed against human MRP1, was able to sensitize canMRP1-expressing cells to
      vincristine. The modulation of canMRP1 by LY402913 was additionally confirmed by
      the calcein-AM accumulation assay. LY402913 inhibited the efflux of calcein in
      canMRP1-expressing cells. Thus, canMRP1 is similar to MRP1 in conferring
      resistance to vincristine and etoposide, transporting calcein-a.m., and being
      inhibited by LY402913. However, despite the high degree of sequence identity and
      functional similarity to MRP1, canMRP1 transgene failed to confer resistance to
      doxorubicin either in HeLa or A2780 cells. Knowledge of species differences
      between canine and human proteins will aid in the design of appropriate
      pharmacokinetic and toxicokinetic studies for the preclinical evaluation of MRP1
      modulators.

PMID- 12516968
TI  - Fas-mediated signaling enhances sensitivity of human soft tissue sarcoma cells to
      anticancer drugs by activation of p38 kinase.
AB  - Sensitivity of human soft tissue sarcoma (STS) cells to methotrexate,
      doxorubicin, and paclitaxel was examined after cells were pretreated with CH-11,
      an agonistic anti-Fas antibody. A subtoxic dose (6 ng/ml) of CH-11 sensitized STS
      cells but not normal fibroblast cells to these anticancer drugs. CH-11 increased
      cytochrome c release and consequent activation of caspase-9, independent of
      caspase-8 and increased p38 activation. Addition of SB203580, a specific
      inhibitor of p38, resulted in a decrease in activation of this kinase and
      abrogation of enhanced chemosensitivity (doxorubicin and paclitaxel) by CH-11.
      These results demonstrate that stimulation of the Fas pathway by a subtoxic dose
      of a Fas agonist can selectively enhance sensitivity of STS cells to certain
      chemotherapeutic agents through activation of p38.

PMID- 12516969
TI  - Neutralizing anti-insulin-like growth factor receptor 1 antibodies inhibit
      receptor function and induce receptor degradation in tumor cells.
AB  - Insulin-like growth factor receptor 1 (IGFR1) plays a crucial role in oncogenic
      transformation [C. Sell et al., Mol. Cell. Biol., 14: 3604-3612,1994]. Compared
      with the normal human mammary epithelial cell line MCF12A, MCF7 human mammary
      carcinoma cells overexpress IGFR1 on the cell surface. To measure the effects of
      IGFR1 inhibition on tumor cells, we tested two mouse neutralizing antibodies
      against human IGFR1 in cell-based assays. Both MAB391 and anti-IR3 antibodies
      inhibit IGFR1 autophosphorylation upon IGF-I ligand stimulation with IC50s of
      0.58 and 0.80 nM, respectively. When cells were treated with neutralizing anti
      IGFR1 antibodies for > or = 4 h, the total receptor level was dramatically
      decreased. IGF-I-stimulated activation of AKT was also inhibited by anti-IGFR1
      antibodies. Furthermore, MAB391 and anti-IR3 inhibited the growth of MCF7 cells
      in soft agar. In addition to MCF7 cells, MAB391 also inhibited IGFR1
      autophosphorylation and induced IGFR1 down-modulation in HT29 colorectal and
      Du145 prostate cancer cells. Therefore, neutralizing antibodies against IGFR1
      represent a valid approach to inhibit growth of tumor cells.

PMID- 12516970
TI  - Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the
      development of pharmacological inhibitors.
AB  - Activation of beta-catenin is a critical step in the pathogenesis of many common
      human cancers and is the initiating event in adenocarcinoma of the colon. Because
      activation of beta-catenin provides a gain-of-function, it is tempting to
      speculate that specific pharmacological inhibition of activated beta-catenin
      might reverse the tumorigenic properties of human cancer cells and therefore form
      the basis of an effective anticancer strategy. In an effort to provide proof-of
      principle for such a strategy, we used a novel clonal growth assay based on human
      somatic cell gene targeting to determine whether activated beta-catenin remains a
      necessary oncogenic stimulus in advanced human cancer cells. Using this approach,
      we demonstrate that beta-catenin is a necessary oncogene in human SW48 and DLD1
      colon cancer cells but not in HCT116 cells. These data indicate that activated
      beta-catenin can remain a critical oncogenic stimulus throughout the progression
      of human colon cancer and suggest that the small molecule inhibitors of activated
      beta-catenin currently under development will be effective anticancer
      therapeutics in a subset of malignant colon cancers.

PMID- 12516971
TI  - Synopsis of a research roundtable presented on cell signaling in myeloma:
      regulation of growth and apoptosis--opportunities for new drug discovery.
AB  - A wide variety of alterations affect important cell-signaling pathways involved
      in growth, survival, and migration of myeloma cells. Several of these pathways
      have been identified, and a number of potential anticancer agents are in
      development to block specific cell signaling proteins. The fifth experts'
      roundtable in multiple myeloma was convened in May 2001 to focus on this
      important issue. The roundtable brought together myeloma experts, researchers
      involved in cell signaling, industry scientists, and investigators studying other
      hematologic malignancies, with the single purpose of challenging current thought
      and increasing the collective knowledge in the evolving field of cell signaling
      and multiple myeloma. The session was cochaired by Dr. William S. Dalton of the
      H. Lee Moffitt Cancer Center and Dr. Kenneth C. Anderson of the Dana-Farber
      Cancer Institute. Sponsored by the Dana-Farber Cancer Institute, the roundtable
      was funded by the Multiple Myeloma Research Foundation and McCarty Cancer
      Foundation of Canada.

PMID- 12516972
TI  - Anatomy and physiology of the perionychium.
AB  - Only primates have a perionychium on the dorsal distal portion of each finger and
      each toe. The flat nail on the end of the human finger allows for increased
      sensory perception in the pad of the finger and for efficient and accurate
      picking up of small objects. It also serves as a guard to protect the very
      sensate fingertip, and functions as a temperature regulator. Nail loss or
      deformity can be not only an aesthetic but also a functional problem. This
      article details the anatomy and physiology of the perionychium, knowledge that is
      essential to providing optimum care for these specialized structures.

PMID- 12516973
TI  - Acute nail bed injuries.
AB  - Although many consider the fingertip injury a very mundane and simple problem,
      the mismanagement of this injury can often lead to a chronic esthetic and
      possibly painful deformity. As noted in this article, the appropriate
      understanding of the involved structures of a fingertip injury as well as the
      meticulous management of these injuries can generally lead to a very esthetic and
      functional fingertip. As previously noted by Elvin Zook, there is probably
      nowhere that Meskimen's Law, "There is never time to do it right but there is
      always time to do it over," is more true.

PMID- 12516974
TI  - Reconstruction of a functional and aesthetic nail.
AB  - There are many causes for nail deformities, the most common being the result of
      trauma or pressure caused by infections, tumors, congenital anomalies, and
      irregularity of the underlying bone or unknown causes such as the pincer nail.
      The corrective treatment of the more common of these will be discussed in this
      and other articles. Examples of nail reconstructions have been described in the
      1990 Hand Clinics and as a rule will not be repeated here.

PMID- 12516975
TI  - Perionychial grafts in trauma and reconstruction.
AB  - With careful attention to anatomic repair and by replacing missing tissue with
      similar tissue, corrections in emergency situations can be accomplished with
      predictably good results. Even in the most complex of injuries, normal nails are
      the expectation rather than the surprise endpoint of surgical repair. Improved
      results in the treatment of chronic nail deformities encourage a bolder surgical
      stance when patients present with nail deformities. Although more work needs to
      be done in the field of total nail replacement, a well-performed full-thickness
      composite graft in carefully selected and prepared patients may be an appropriate
      solution to a problem that has been ignored too often.

PMID- 12516976
TI  - Microtransfers for nail and fingertip replacement.
AB  - We have reported the cases of vascularized nail flap transfer with a short
      pedicle fashion. We consider that reconstruction of fingers should be conducted
      positively, even in the case of the nail defect, except the thumb. Because these
      operations are aimed at aesthetic improvement, reconstruction with a short
      pedicle fashion seems to be the method worth employing because it leaves short
      skin incisions. The final goal of nail surgery is for the patients to use the
      reconstructed finger in public. To achieve this goal, we must keep in our mind
      the aesthetic considerations in nail surgery.

PMID- 12516977
TI  - Nail fungal infections and treatment.
AB  - Treating onychomycosis may be a tantalizing problem depending on the age of the
      patient, the condition's modifications, and the status of the peripheral
      circulation. The clinician will have to choose among three main possibilities:
      topical therapy with the new nail lacquers, new oral drugs, and removal of the
      nail plate. A combination of different modalities often provides the best option.

PMID- 12516978
TI  - Fungal infections of the perionychium.
AB  - There are two types of fungi (yeasts and molds) both of which can cause
      superficial infections of the perionychium. Yeasts (such as Candida albicans)
      grow as single cells and reproduce by asexual budding. In contrast, molds grow in
      long filaments, called hyphae. There are approximately 100,000 species of fungi
      that have been characterized. Most of these are ubiquitous. Fortunately only
      about 200 are human pathogens, and only a handful are commonly found to be
      associated with human disease. This article discusses causes, symptoms,
      diagnosis, and treatment of the most common fungal infections of the
      perionychium, including superficial dermatophytosis, onychomycosis, and chronic
      paronychia.

PMID- 12516979
TI  - Harnessing the osseointegration principle for anchorage of fingernail prostheses.
AB  - On the basis of this preliminary report series of patients, it seems that the
      achievement of fixed anchorage for nail prostheses is feasible using the process
      of osseointegration, the use of standard dental implants, and abutment and
      maxillofacial rehabilitation laboratory to build the superstructure system. The
      osseointegrated procedure is relatively simple, cost-effective, and less time
      consuming compared with other reconstruction techniques. Using local anesthesia
      and day-care facilities the operative time was only 35 minutes for the first
      stage and 15 minutes for the second stage. The attachment should be lifelong, as
      in the face. Loosening and infection are infrequent.

PMID- 12516980
TI  - Imaging of the tumors of the perionychium.
AB  - Despite the high value of clinical examination of the perionychium, radiography
      remains necessary if one suspects a deep mass beneath the nail plate.
      Ultrasonography may be helpful in experienced hands to depict cystic or vascular
      lesions, but MRI offers the most promising developments for imaging the
      perionychium.

PMID- 12516981
TI  - Tumors of the perionychium.
AB  - Tumors of the perionychium are often subtle and difficult to diagnose. Because
      they are somewhat uncommon, the early symptoms of these tumors, which may include
      vague pain, local swelling, nail discoloration, nail deformity, or drainage, may
      be mistaken for signs of infection and/or trauma and therefore treated with
      topical or oral antibiotics for some time. Functionally important in enhancing
      fingertip sensation, protection, and manipulating fine objects, the perionychium
      is continuously subject to day-to-day trauma and injury that can alter the
      natural contours and growth patterns of the nail plate. Bacterial, viral, or
      fungal infections can incite swelling, pain, and distortion of the perionychium
      as well. Both infection and trauma, then, can mask underlying tumors or growths
      that would delay their diagnosis. A delay in treatment can be devastating if the
      growth of the perionychium happens to be malignant. Therefore, a general
      understanding of the signs and symptoms of the perionychium tumors is needed by
      all physicians and surgeons treating nail problems.

PMID- 12516982
TI  - Matricectomy and nail ablation.
AB  - Matricectomy refers to the complete extirpation of the nail matrix, resulting in
      permanent nail loss. Usually however, matricectomy is only partial, restricted to
      one or both lateral horns of the matrix. Nail ablation is the definitive removal
      of the entire nail organ. The most important common denominator in the successful
      matricectomy is the total removal or destruction of the matrix tissue.
      Matricectomy may be indicated for the management of onychauxis, onychogryphosis,
      congenital nail dystrophies, and chronic painful nail, such as recalcitrant
      ingrown toenail or split within the medial or lateral one-third of the nail.

PMID- 12516983
TI  - Statistical issues in cost-effectiveness analyses.

PMID- 12516984
TI  - Analysis of uncertainty in health care cost-effectiveness studies: an
      introduction to statistical issues and methods.
AB  - Cost-effectiveness analysis is now an integral part of health technology
      assessment and addresses the question of whether a new treatment or other health
      care program offers good value for money. In this paper we introduce the basic
      framework for decision making with cost-effectiveness data and then review recent
      developments in statistical methods for analysis of uncertainty when cost
      effectiveness estimates are based on observed data from a clinical trial.
      Although much research has focused on methods for calculating confidence
      intervals for cost-effectiveness ratios using bootstrapping or Fieller's method,
      these calculations can be problematic with a ratio-based statistic where
      numerator and/or denominator can be zero. We advocate plotting the joint density
      of cost and effect differences, together with cumulative density plots known as
      cost-effectiveness acceptability curves (CEACs) to summarize the overall value
      for-money of interventions. We also outline the net-benefit formulation of the
      cost-effectiveness problem and show that it has particular advantages over the
      standard incremental cost-effectiveness ratio formulation.

PMID- 12516985
TI  - Bayesian methods for design and analysis of cost-effectiveness trials in the
      evaluation of health care technologies.
AB  - We review the development of Bayesian statistical methods for the design and
      analysis of randomized controlled trials in the assessment of the cost
      effectiveness of health care technologies. We place particular emphasis on the
      benefits of the Bayesian approach; the implications of skew cost data; the need
      to model the data appropriately to generate efficient and robust inferences
      instead of relying on distribution-free methods; the importance of making full
      use of quantitative and structural prior information to produce realistic
      inferences; and issues in the determination of sample size. Several new examples
      are presented to illustrate the methods. We conclude with a discussion of the key
      areas for future research.

PMID- 12516986
TI  - Decision analytical economic modelling within a Bayesian framework: application
      to prophylactic antibiotics use for caesarean section.
AB  - Economic evaluation of health care interventions based on decision analytic
      modelling can generate valuable information for health policy decision makers.
      However, the usefulness of the results obtained depends on the quality of the
      data input into the model; that is, the accuracy of the estimates for the costs,
      effectiveness, and transition probabilities between the different health states
      of the model. The aim of this paper is to review the use of Bayesian decision
      models in economic evaluation and to demonstrate how the individual components
      required for decision analytical modelling (i.e., systematic review incorporating
      meta-analyses, estimation of transition probabilities, evaluation of the model,
      and sensitivity analysis) may be addressed simultaneously in one coherent
      Bayesian model evaluated using Markov Chain Monte Carlo simulation implemented in
      the specialist Bayesian statistics software WinBUGS. To illustrate the method
      described, a simple probabilistic decision model is developed to evaluate the
      cost implications of using prophylactic antibiotics in caesarean section to
      reduce the incidence of wound infection. The advantages of using the Bayesian
      statistical approach outlined compared to the conventional classical approaches
      to decision analysis include the ability to: (i) perform all necessary analyses,
      including all intermediate analyses (e.g., meta-analyses) required to derive
      model parameters, in a single coherent model; (ii) incorporate expert opinion
      either directly or regarding the relative credibility of different data sources;
      (iii) use the actual posterior distributions for parameters of interest (opposed
      to making distributional assumptions necessary for the classical formulation);
      and (iv) incorporate uncertainty for all model parameters.

PMID- 12516987
TI  - Measuring uncertainty in complex decision analysis models.
AB  - Prediction models used in support of clinical and health policy decision making
      often need to consider the course of a disease over an extended period of time,
      and draw evidence from a broad knowledge base, including epidemiologic cohort and
      case control studies, randomized clinical trials, expert opinions, and more. This
      paper is a brief introduction to these complex decision models, their relation to
      Bayesian decision theory, and the tools typically used to describe the
      uncertainties involved. Concepts are illustrated throughout via a simplified
      tutorial.

PMID- 12516988
TI  - Using inverse-weighting in cost-effectiveness analysis with censored data.
AB  - Due to induced dependent censoring, estimating mean costs and quality-adjusted
      survival in a cost-effectiveness analysis using standard life-table methods leads
      to biased results. In this paper we propose methods for estimating the difference
      in mean costs and the difference in effectiveness, together with their respective
      variances and covariance in the presence of dependent censoring. We consider the
      situation in which the measure of effectiveness is either the probability of
      patients surviving a duration of interest, mean survival time over a duration of
      interest or mean quality-adjusted survival time over a duration of interest. The
      method of inverse-weighting is used for censored cost and quality of life data.
      The methods are illustrated in an example using an incremental net benefit
      analysis.

PMID- 12516989
TI  - Navigating the new "golden age" of clinical research.

PMID- 12516990
TI  - Views from the trenches: clinician-scientist trainees speak up.

PMID- 12516991
TI  - How to look for an academic position.

PMID- 12516992
TI  - Na+/H+ exchange: molecular regulation to therapeutic development.

PMID- 12516993
TI  - Nocturnal hemodialysis: an attempt to correct the "unphysiology" of conventional
      intermittent renal replacement therapy.

PMID- 12516994
TI  - Patient profiles at a centralized, urban, diabetes education centre.
AB  - BACKGROUND: Little is known about the characteristics of patients attending
      diabetes education centres (DECs). To address this knowledge gap, we examined the
      clinical characteristics of patients referred to a centralized urban DEC.
      METHODS: Using a clinically detailed patient registry, we studied the profiles of
      1459 patients seen in an urban DEC, and compared patients referred to the DEC by
      family physicians (FPs) to those referred by other physicians (usually
      specialists), and patients referred to the DEC for the first time to those who
      had been referred a number of times (multiply-referred patients). RESULTS: Among
      patients with a known source of referral, 73% were referred by their FP and 27%
      by a physician other than the FP. Eighty-seven percent of patients were being
      referred for the first time, and 13% had previous referrals. Blood glucose
      control at the time of referral was poorer for non-FP referrals and for multiply
      referred patients. Patients in the former subgroup were more likely taking
      insulin when referred (38% v. 12%, p < 0.000), to have type 1 diabetes (19% v.
      8%, p < 0.000) and to be referred for insulin initiation (12% v. 2%, p < 0.000)
      than were FP referrals. Meanwhile, multiply-referred patients were younger (51.9
      v. 56.1 yr, p < 0.000) and were more likely to be female (59% v. 46%, p = 0.001)
      than were patients referred only once. INTERPRETATION: Source of referral (FP v.
      non-FP) and presence or absence of previous referrals define unique DEC patient
      subgroups. Attention to the relative size and service needs of these subgroups is
      relevant to the planning of diabetes services.

PMID- 12516995
TI  - Simultaneous administration of meningococcal C conjugate vaccine and diphtheria
      tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b
      conjugate vaccine in children: a randomized double-blind study.
AB  - BACKGROUND: Meningococcal C disease can be life-threatening in infants, young
      children and adolescents. New conjugate vaccines are immunogenic in young infants
      and induce immunologic memory, so we should consider incorporating them into the
      routine childhood immunization program. The objective of this study was to
      measure the safety and immunogenicity of a meningococcal C conjugate vaccine when
      given with routine childhood vaccines. METHODS: We carried out a randomized,
      double-blind, controlled clinical trial at children's hospitals in 3 Canadian
      cities. A convenience sample of 351 healthy 2-month-old infants was enrolled from
      the community and randomly allocated to receive either meningococcal C conjugate
      vaccine or the control (hepatitis B) vaccine. All participants received a
      concurrent injection of the combined diphtheria-tetanus-acellular pertussis
      inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) conjugate
      vaccine in the opposite limb. Participants were immunized at 2, 4, 6 and 15
      months of age; adverse events were recorded after each dose. Serum bactericidal
      and ELISA meningococcal antibody levels in the participants were measured at 6,
      7, 15 and 16 months of age; diphtheria, tetanus, H. influenzae type b, poliovirus
      and pertussis antibodies were measured at 7 months of age. A total of 323 (92%)
      participants completed all aspects of the study. The proportion of participants
      who suffered adverse events after each vaccine dose was the primary safety
      outcome. Geometric mean antibody titres and the proportion of participants with
      protective antibody levels after immunization were the primary immunologic
      outcomes. RESULTS: After 2 doses of the meningococcal C conjugate vaccine 99% of
      participants achieved a protective ( > or = 1:8) bactericidal meningococcal
      serogroup C antibody level, and after 3 doses this rate increased to 100%.
      Antibody levels to the concomitant vaccine antigens in the group receiving
      meningococcal C vaccine were similar to those in the control group except for
      higher antidiphtheria antibody titres (p < 0.001). Local injection site reactions
      (redness and induration) after the meningococcal conjugate vaccine were more
      frequent than after hepatitis B vaccine but less frequent than after the DTaP-IPV
      Hib vaccine. CONCLUSIONS: The meningococcal C conjugate vaccine can be safely and
      effectively administered at the same visit as the other vaccine antigens
      routinely given to infants in Canada.

PMID- 12516996
TI  - DNA databanks, public opinion and the law.

PMID- 12516997
TI  - Who was that guy?

PMID- 12516998
TI  - Are clinician-scientists an endangered species? Barriers to clinician-scientist
      training.

PMID- 12516999
TI  - Innate immunity to malaria caused by Plasmodium falciparum.
AB  - Malaria, a widespread disease caused by protozoa of the genus Plasmodium,
      contributes to the death of more than 2 million people each year. Resistance to
      antimalarial drugs is increasing, and an effective vaccine has not yet been
      designed. In the search for alternative means to control malaria infections,
      especially those caused by the most lethal species of malaria parasite,
      Plasmodium falciparum, our attention has turned to elucidating the relationships
      of the parasite and human host at the molecular level. In this review, we
      describe possible mechanisms by which naturally occurring genetic mutations might
      confer resistance to P. falciparum and how our innate immune response mediated by
      the phagocytic action of monocytes and macrophages acts as a first-line defence
      in clearing malaria infections. The potential effectiveness of novel therapies to
      enhance innate phagocytic clearance of malaria parasites, particularly in
      nonimmune people who are at greatest risk of adverse outcomes, is also discussed.

PMID- 12517000
TI  - Detection of Taura syndrome virus (TSV) strain differences using selected
      diagnostic methods: diagnostic implications in penaeid shrimp.
AB  - Anecdotal industry reports of Taura syndrome (TS) epizootics in a Taura syndrome
      virus (TSV) tolerant strain of Penaeus stylirostris and collected evidence of
      field TS epizootics in P. stylirostris suggested that a distinct new TSV strain
      might have emerged since 1994. The Ecuadorian 1992 TSV genome published in
      GenBank is virtually identical to the Hawaiian 1994 TSV isolate (HI94TSV) used as
      reference throughout this investigation. Three other geographic and year isolates
      of TSV from naturally occurring TS epizootics of cultured penaeid shrimp were
      obtained from Mexico (SIN98TSV and MX99TSV from P. vannamei and SON2KTSV from P.
      stylirostris). Selected TSV diagnostic methods set forth by the Office
      International des Epizooties were utilized as the basis for isolate analysis. By
      Southern blot, TSV probes P15 and Q1 reacted specifically with all the diagnostic
      reverse transcription polymerase chain reaction (RT-PCR) fragments. Additionally,
      labeled RT-PCR amplicons from the TSV isolates amplified by routine diagnostic RT
      PCR primers gave positive in situ hybridizations with TSV, indicating that all 4
      isolates shared homology. By Western blot, immuno-dot blot, and
      immunohistochemistry, all TSV-purified isolates reacted with TSV polyclonal
      antibody (PAb). However, with TSV monoclonal antibody (MAb) 1A1 all isolates,
      except SIN98TSV, reacted, indicating that the difference in isolate SIN98TSV is
      within VP1, the target for MAb 1A1. The amino acid (AA) sequence of SIN98TSV VP1,
      MX99TSV VP1 and SON2KTSV VP1 has a 98% homology with the reference HI94TSV VP1. A
      span of 12 AAs are identified in SIN98TSV VP1 containing significant AA
      substitutions which may account for a conformational change of the antigenic
      epitope sufficient to prevent MAb 1A1 from binding. The implications of these
      results with respect to the antibody-based diagnosis of TSV are discussed.

PMID- 12517001
TI  - Cardiac performance in Salmo salar with infectious salmon anaemia (ISA): putative
      role of nitric oxide.
AB  - Infectious salmon anaemia (ISA) is a viral disease which targets the vascular and
      endocardial endothelial cells. An in vitro preparation of the spontaneously
      beating working heart of Salmo salar L. (i.e. able to generate physiological
      values of output pressure, cardiac output, ventricle work and power) was used to
      study cardiac performance under basal (i.e. in the absence of stimuli) and
      loading (i.e. Frank-Starling response) conditions in both control and ISAV
      affected fish. In contrast to control fish, the heart preparations of the
      infected counterparts showed an impairment of the Frank-Starling response,
      particularly evident in fish infected with a higher virus dose. The Frank
      Starling response was progressively impaired with the progression of the viral
      disease from the time of the virus administration until the 20th day. The
      potential involvement of nitric oxide (NO) in cardiac dysfunction was
      investigated by using the authentic nitric oxide synthase (NOS) substrate L
      arginine and the NOS inhibitors L-NMMA and L-NIL. In contrast to control fish,
      infected hearts were particularly sensitive to the inducible nitric oxide
      synthase (iNOS) inhibitor L-NIL and insensitive to L-arginine. While pretreatment
      with NOS inhibitors reduced the Frank-Starling response in control hearts, it
      restored this response in infected counterparts. Taken together, the results
      indicate that cardiac dysfunction and the NO-transduction-pathway can be
      mechanistically linked in infected salmon.

PMID- 12517002
TI  - Occurrence of viral haemorrhagic septicaemia virus (VHSV) in wild marine fish
      species in the coastal regions of Norway.
AB  - This study was aimed at determining the occurrence of viral haemorrhagic
      septicaemia virus (VHSV) in selected stocks of wild fish species in the coastal
      regions of Norway. Six cruises were undertaken covering areas which included the
      coastal regions of northern Norway, the Norwegian Sea, the Barents Sea, and the
      Skagerrak area down to the Danish border. Collected, pooled samples of internal
      organs (kidney, spleen and heart) from 8395 fish were examined for the presence
      of VHSV by inoculation on BF-2 cells. Identification of virus was performed by a
      standard ELISA procedure with monoclonal antibody IP5B11, which is specific for
      the VHSV nucleocapsid protein (N-protein). VHSV was isolated from blue whiting
      and Norway pout in Skagerrak. No positive samples were detected in the northern
      coastal regions of Norway, the Norwegian Sea, or the Barents Sea. The findings
      indicate a very low occurrence of VHSV in the coastal regions of Norway.
      Geographically, the only positive samples were obtained from fish collected in
      areas where VHSV has previously been found in different species of fish.

PMID- 12517003
TI  - Phylogenetic analysis of viral haemorrhagic septicaemia virus (VHSV) isolates
      from France (1971-1999).
AB  - The nucleotide sequences of a specific region of the glycoprotein gene were
      compared among 63 strains of viral haemorrhagic septicaemia virus (VHSV) isolated
      from fish in France between 1971 and 1999. The analysis was performed on a region
      corresponding to amino acids 238 to 331 of the glycoprotein gene, also designated
      the V2 region and previously shown to accumulate most of the mutations. The
      sequences of many VHSV isolates were found to be identical or very conserved. An
      isolate, designated L59X, obtained from elver in the Loire estuary, depicted a
      higher degree of divergence compared to the other French isolates. The deduced
      amino-acid sequences were analysed together with the results of neutralisation
      tests performed using monoclonal antibody 168m4 specific to serotype 1. Non
      neutralised VHSV strains had mutations in the region corresponding to the
      previously described 168m4 epitope. Phylogenetic analysis showed that all the
      VHSV isolates studied, except L59X, belong to genotype I, previously described as
      containing VHSV strains isolated from continental Europe. Most of the VHSV
      isolates studied were found to be genetically related to one of the previously
      described VHSV strains representative of the major serotypes. Isolate L59X, which
      was the only French marine strain studied, was found to belong to genotype II,
      previously shown to encompass the VHSV strains isolated from the British Isles
      coastal waters. Overall there was a good correlation between the geographical
      origin of the studied isolates and their genetic characteristics.

PMID- 12517005
TI  - Temperature effect on the immune defense functions of Arctic charr Salvelinus
      alpinus.
AB  - The Arctic charr Salvelinus alpinus is an endangered fish species in Finland, and
      thus farming is carried out mainly for stocking purposes. Farmed charr are
      susceptible to infection with atypical Aeromonas salmonicida (aAS). Losses of
      valuable brood stock will severely reduce the genetic diversity of stocked charr.
      No commercial vaccines are available to prevent aAS infection, and vaccines
      against furunculosis (caused by typical A. salmonicida, tAS) do not protect the
      charr against aAS infection. The effects of a metabolizable oil-adjuvanted,
      bivalent vaccine (containing killed aAS and A. salmonicida salmonicida bacteria)
      on the immune system of 1 yr old hatchery-reared charr originating from Lake
      Inari in Northern Finland were examined. Fish vaccination in Finland generally
      takes place either from October to November or from February to April, when the
      water temperature is low (1 to 3degrees C). The water temperature starts to
      increase in mid-May. Therefore, we also investigated whether post-vaccination
      (p.v.) temperature had an influence on the immune system of this cold-water fish
      species. The fish were immunized intraperitoneally at 2.9 degrees C at the end of
      April. After 52 d, during which the water temperature increased from 2.9 to 10.0
      degrees C, the charr were exposed to 1 of 3 test temperatures: 10.3, 14.1 or 18.1
      degrees C. Prior to vaccination, and 49, 75 and 103 d p.v., several immune
      parameters were measured in both unvaccinated and vaccinated charr. Vaccination
      induced a significant anti-aAS-specific antibody response, and increased plasma
      lysozyme activity at all p.v. temperatures. The haemolytic activity of the
      complement system was unaffected either by vaccination or p.v. temperatures.
      There was a slight positive correlation between p.v. temperature and lysozyme
      activity of the charr. The significant increase in lysozyme activity took place
      in vaccinated charr in the first 49 d p.v. as water temperatures increased from
      2.9 to 10 degrees C. Furthermore, the highest activity of lysozyme in the plasma
      was observed 49 d p.v. Our results indicate that a rise in water temperature
      above 10 degrees C does not significantly enhance the vaccination response of
      charr. This could be one reason why farmed Arctic charr, which are well adapted
      to a cold climate, are highly susceptible to aAS infection in the summer.

PMID- 12517004
TI  - 16S ribosomal DNA sequencing confirms the synonymy of Vibrio harveyi and V.
      carchariae.
AB  - Seventeen bacterial strains previously identified as Vibrio harveyi (Baumann et
      al. 1981) or V. carchariae (Grimes et al. 1984) and the type strains of V.
      harveyi, V. carchariae and V. campbellii were analyzed by 16S ribosomal DNA
      (rDNA) sequencing. Four clusters were identified in a phylogenetic analysis
      performed by comparing a 746 base pair fragment of the 16S rDNA and previously
      published sequences of other closely related Vibrio species. The type strains of
      V. harveyi and V. carchariae and about half of the strains identified as V.
      harveyi or V. carchariae formed a single, well-supported cluster designed as
      'bona fide' V. harveyi/carchariae. A second more heterogeneous cluster included
      most other strains and the V. campbellii type strain. Two remaining strains are
      shown to be more closely related to V. rumoiensis and V. mediterranei. 16S rDNA
      sequencing has confirmed the homogeneity and synonymy of V. harveyi and V.
      carchariae. Analysis of API20E biochemical profiles revealed that they are
      insufficient by themselves to differentiate V. harveyi and V. campbellii strains.
      16S rDNA sequencing, however, can be used in conjunction with biochemical
      techniques to provide a reliable method of distinguishing V. harveyi from other
      closely related species.

PMID- 12517006
TI  - Susceptibility of rainbow trout Oncorhynchus mykiss, Atlantic salmon Salmo salar
      and coho salmon Oncorhynchus kisutch to experimental infection with sea lice
      Lepeophtheirus salmonis.
AB  - Physiological, immunological and biochemical parameters of blood and mucus, as
      well as skin histology, were compared in 3 salmonid species (rainbow trout
      Oncorhynchus mykiss, Atlantic salmon Salmo salar and coho salmon O. kisutch)
      following experimental infection with sea lice Lepeophtheirus salmonis. The 3
      salmonid species were cohabited in order to standardize initial infection
      conditions. Lice density was significantly reduced on coho salmon within 7 to 14
      d, while lice persisted in higher numbers on rainbow trout and Atlantic salmon.
      Lice matured more slowly on coho salmon than on the other 2 species, and
      maturation was slightly slower on rainbow trout than on Atlantic salmon. Head
      kidney macrophages from infected Atlantic salmon had diminished respiratory burst
      and phagocytic capacity at 14 and 21 d post-infection (dpi), while infected
      rainbow trout macrophages had reduced respiratory burst and phagocytic capacities
      at 21 dpi, compared to controls. The slower development of lice, coupled with
      delayed suppression of immune parameters, suggests that rainbow trout are
      slightly more resistant to lice than Atlantic salmon. Infected rainbow trout and
      Atlantic salmon showed increases in mucus lysozyme activities at 1 dpi, which
      decreased over the rest of the study. Mucus lysozyme activities of infected
      rainbow trout, however, remained higher than controls over the entire period.
      Coho salmon lysozyme activities did not increase in infected fish until 21 dpi.
      Mucus alkaline phosphatase levels were also higher in infected Atlantic salmon
      compared to controls at 3 and 21 dpi. Low molecular weight (LMW) proteases
      increased in infected rainbow trout and Atlantic salmon between 14 and 21 dpi.
      Histological analysis of the outer epithelium revealed mucus cell hypertrophy in
      rainbow trout and Atlantic salmon following infection. Plasma cortisol, glucose,
      electrolyte and protein concentrations and hematocrit all remained within
      physiological limits for each species, with no differences occurring between
      infected and control fish. Our results demonstrate that significant differences
      in mucus biochemistry and numbers of L. salmonis occur between these species.

PMID- 12517007
TI  - Toxicity and pathological effects of orally and intraperitoneally administered
      ivermectin on sea bass Dicentrarchus labrax.
AB  - The toxicity and histopathology of ivermectin was studied in 3 and 35 g sea bass
      Dicentrarchus labrax L. following in-feed, oral intubation and injection
      administration at dose rates ranging from 0.5 to 3.5 mg kg(-1). Estimated LD50
      values for 3 g fish were 0.335 and 0.106 mg kg(-1) following oral intubation and
      injection administration respectively, for fish reared at 11 degrees C; and 0.839
      and 1.023 mg kg(-1) following oral intubation and injection administration,
      respectively for fish reared at 20 degrees C. For 35 g fish reared at 11 degrees
      C, the estimated LD50 was 0.523 and 0.361 mg kg(-1) following oral intubation and
      injection administration respectively. No signs of toxicity were observed when
      the compound was administered via the feed at 0.5 and 0.7 mg kg(-1). However,
      toxicity (> 10%) was observed at dose rates of 0.2 mg kg(-1) and higher when the
      compound was administered via oral intubation and at 0.5 mg kg(-1) when
      administered via injection. The compound was significantly more toxic to fish
      reared at 11 degrees C than at 20 degrees C. Further, ivermectin was more toxic
      to 3 g than to 35 g sea bass when administered via injection. Histopathological
      examination of the major organs revealed pathology was largely restricted to
      gills and intestinal tissue. In 3 g sea bass, lesions were also found in the
      kidneys.

PMID- 12517008
TI  - Insights into fish host-parasite trophic relationships revealed by stable isotope
      analysis.
AB  - Trophic relationships between 10 species of fish host and their associated
      nematode, cestode, and copepod parasites were investigated using stable isotopes
      of carbon and nitrogen. Nematodes and cestodes were consistently depleted in 15N
      with respect to their host, and such fractionation patterns are unlike those
      conventionally observed between consumers and their diets. Species of copepod
      parasite were sometimes depleted and sometimes enriched in 15N with respect to
      fish hosts, and this confirms earlier reports that the nature and magnitude of
      ectoparasite-host fractionations can vary. Significant differences in delta15N
      and delta13C were observed among fish tissues, and the isotopic signature of
      parasites did not always closely correspond to that of the tissue with which the
      parasite was found most closely associated, or on which the parasite was thought
      to be feeding. Several possible explanations are considered for such
      discrepancies, including selective feeding on specific amino acids or lipids,
      migration of the parasite among different fish tissues, changes in the metabolism
      of the parasite associated with life history and migration between different host
      animals.

PMID- 12517009
TI  - Mycobacterial infection in farmed turbot Scophthalmus maximus.
AB  - Mycobacteriosis (piscine tuberculosis) has been reported to affect a wide range
      of freshwater and marine fish species; however, this is the first report
      describing mycobacterial infections in turbot Scophthalmus maximus. High numbers
      of granulomas were initially observed in the organs of moribund farmed turbot.
      Bacteriological analysis of organs with granulomas led to the isolation of
      Mycobacterium marinum. Further analysis, to determine the prevalence of the
      infection in the farm and to identify its source, showed the occurrence of a dual
      infection by M. marinum and M. chelonae. The presence of Nocardia sp. in some of
      the fish infected with mycobacteria was also detected. The presence of granulomas
      in internal organs of apparently healthy fish indicated a high prevalence of the
      disease, a conclusion that was supported by isolating mycobacteria from all fish
      with or without granulomas. The infection was probably responsible for the
      mortality observed (approximately 2% mo(-1)), as most of the recently dead fish
      presented high numbers of granulomas and isolation of mycobacteria was possible
      from all of the fish. The isolation of M. marinum from the inlet water suggested
      this as the most plausible source for the infection occurring in the farm.

PMID- 12517010
TI  - Occupational risk of blood-borne viruses in healthcare workers.

PMID- 12517011
TI  - Bloodstream infections in hemodialysis patients: getting some deserved attention.

PMID- 12517012
TI  - Prospective surveillance for primary bloodstream infections occurring in Canadian
      hemodialysis units.
AB  - OBJECTIVE: Bloodstream infections are a major cause of morbidity and mortality in
      patients receiving long-term hemodialysis. We wanted to determine the incidence
      of hemodialysis-related bloodstream infections in Canadian centers participating
      in the Canadian Nosocomial Infection Surveillance Program. METHODS: Prospective
      surveillance for hemodialysis-related bloodstream infections was performed in 11
      centers during a 6-month period. Bloodstream infections were defined by published
      criteria. Hemodialysis denominators included the number of dialysis procedures,
      the number of patient-days on dialysis, and the frequencies of different types of
      vascular access. RESULTS: There were 184 bloodstream infections in 133,158
      dialysis procedures (1.4 per 1,000) and 316,953 patient-days (0.6 per 1,000).
      Hemodialysis access through arteriovenous (AV) fistulae was associated with the
      lowest risk for bloodstream infection (0.2 per 1,000 dialysis procedures). The
      relative risk for infection was 2.5 with AV graft access, 15.5 with cuffed and
      tunneled central venous catheter (CVC) access, and 22.5 with uncuffed CVC access
      (P < .001). There was marked variation among the 11 centers in the means of
      vascular access used for hemodialysis. Significant variation in infection rates
      was observed among the centers when controlling for types of access. CONCLUSIONS:
      There was a hierarchy of risk of hemodialysis-related bloodstream infection
      according to type of vascular access. There was significant variation in the type
      of vascular access being used among the Canadian hemodialysis centers, and also
      variation in access-specific infection rates between centers.

PMID- 12517013
TI  - Surveillance of hemodialysis-associated primary bloodstream infections: the
      experience of ten hospital-based centers.
AB  - OBJECTIVE: To determine baseline rates of primary bloodstream infection (BSI)
      among a large pool of patients receiving hemodialysis using standardized
      surveillance tools and methodology. DESIGN: Prospective, descriptive analysis of
      primary BSI rates. SETTING: Ten hospital-based hemodialysis centers in
      Connecticut. PATIENTS: All patients receiving long-term hemodialysis in the
      participating facilities. RESULTS: A total of 158 BSIs occurred during 142,525
      dialysis sessions within a 12-month study period. Of the BSIs, 15.2% occurred in
      patients with fistula or graft access and 84.8% in patients with central venous
      catheter access (P < .001). Rates per 100 patient-years in centers ranged from 0
      to 30.8, with a mean of 16.6. Rates per 1,000 dialysis sessions ranged from 0 to
      2.1, with a mean of 1.1. Coagulase-negative staphylococci and Staphylococcus
      aureus (including methicillin-resistant S. aureus) accounted for 61% and
      Klebsiella or Enterobacter species for 14.6% of infections. Of the patients,
      63.3% received vancomycin, 24.7% received cefazolin, and 41.7% received
      aminoglycosides. Rates declined in the second 6 months of the study from 1.4 to
      0.8 infections per 1,000 dialysis sessions (P < .001). CONCLUSIONS: Primary BSI
      rates varied widely among participating centers and declined during the study
      period. BSIs were strongly associated with central venous catheter access.
      Further studies are needed to determine the reasons for variance in rates between
      centers and among various types of hemodialysis access.

PMID- 12517014
TI  - An outbreak of bloodstream infections in an outpatient hemodialysis center.
AB  - OBJECTIVES: Investigate and control an increase in bloodstream infections (BSIs)
      in an outpatient hemodialysis center. PATIENTS AND DESIGN: A retrospective cohort
      study was conducted for patients receiving dialysis at the center from February
      2000 to April 2001. A case-control study compared microbiological data for all
      BSIs that occurred during the study period with those for BSIs that occurred
      during a baseline period January 1999 to January 2000). BSI rates before and
      after a 1-month intervention (May 2001) were assessed. A case was defined as a
      new BSI during the study period. RESULTS: The outbreak was polymicrobial, with
      approximately 30 species. The baseline BSI rate was 0.7 per 100 patient-months.
      From February 2000 to April 2001, the BSI rate increased to 4.2 per 100 patient
      months. Overall, 75% of the BSIs were associated with central venous catheters
      (CVCs), but CVC use did not fully explain the increase in BSIs. In January 2000,
      when the center changed ownership, prepackaged CVC dressing kits and biweekly
      infection control monitoring were discontinued. Beginning in May 2001, staff were
      educated on CVC care, chlorhexidine replaced povidone-iodine for cutaneous
      antisepsis, gauze replaced transparent dressings, antimicrobial ointments
      containing polyethylene glycol at CVC exit sites were discontinued, and patients
      with CVCs were educated on cutaneous hygiene. After the intervention period, by
      October 2001, rates decreased to less than 1 BSI per 100 patient-months.
      CONCLUSIONS: Proper cutaneous antisepsis and access site care is crucial in
      preventing BSIs in patients receiving hemodialysis. Infection control programs,
      staff and patient education, and use of optimal antisepsis agents or prepackaged
      kits are useful toward this end.

PMID- 12517015
TI  - Weekly transparent dressing changes linked to increased bacteremia rates.
AB  - BACKGROUND: In 2000, the rate of primary bloodstream infections (BSIs) was double
      that in 1999 for intensive care unit (ICU) patients with triple lumen catheters,
      pulmonary artery catheters, or both. In December 1999, changes in products and
      practices related to site care were implemented as a cost-saving initiative.
      OBJECTIVE: To determine the factors contributing to an increase of BSIs after
      cost-saving measures for site care had been introduced. DESIGN: Epidemiologic
      study involving prospective identification of infection. SETTING: A community
      teaching hospital. PARTICIPANTS: Patients in a 20-bed, medical-surgical ICU
      identified as having triple lumen catheters, pulmonary artery catheters, or both
      and a primary BSI during 2000 and 2001. METHODS: Alcohol swab sticks were
      reintroduced and the frequency of transparent dressing changes and site care was
      increased. Inservice presentations were conducted on aseptic technique and
      posters were placed reviewing site care protocol for physicians and nurses.
      RESULTS: The incidence of primary BSIs decreased significantly (P = .003) during
      a 3-month intervention and this decrease was sustained through the following 12
      months. CONCLUSIONS: Prolonging the interval between the change of transparent
      dressings from 3 times weekly to once weekly and switching from alcohol swab
      sticks to pads was associated with an increase in BSIs, which was controlled
      after returning to the original policy.

PMID- 12517016
TI  - An outbreak of Serratia marcescens bacteremia after general anesthesia.
AB  - OBJECTIVE: To investigate an outbreak of Serratia marcescens bacteremia among
      patients after general anesthesia. DESIGN: A case-control study. SETTING: A 304
      bed, pediatric teaching hospital. PATIENTS: Twenty-three pediatric patients who
      developed S. marcescens bacteremia within 2 weeks after general anesthesia
      between June 15 and September 22, 1999, were compared with 46 age-matched control
      patients who had undergone procedures on the same clinical services of the
      hospital during the same period. RESULTS: Cases were distributed over a wide
      range of surgical services and were not correlated with exposure to any of the
      surgical, anesthesia, or nursing staff. Case-patients were significantly more
      likely than control-patients to have received cefazolin (odds ratio [OR], 11.1;
      90% confidence interval [CI90], 1.9 to 24.3) or to have had perioperative
      placement of a central vascular catheter (OR, 4.2; CI90, 1.2 to 18.8). The timing
      of the procedures of patients who subsequently developed S. marcescens bacteremia
      was significantly associated with the shifts of one or more of five operating
      room technicians (OR, 2.9 to 6.8) who were responsible for preparing intravenous
      fluids used both to reconstitute perioperatively administered antibiotics and to
      prime central vascular catheter assemblies. CONCLUSIONS: Our findings are
      consistent with a pattern of intermittent contamination due to periodic breaches
      in sterile technique, rather than a point-source of contamination. The unique
      challenges that such a procedural breakdown presents to an epidemiologic
      investigation are discussed. This outbreak stresses the importance of providing
      comprehensive training in antisepsis when multifunctional personnel are
      incorporated into an operating room work environment.

PMID- 12517017
TI  - Serratia bacteremia in a large university hospital: trends in antibiotic
      resistance during 10 years and implications for antibiotic use.
AB  - OBJECTIVE: To identify antibiotic resistance trends and risk factors for
      resistance of Serratia species to third-generation cephalosporins. DESIGN:
      Retrospective survey of medical records. SETTING: A 2,200-bed, tertiary-care
      hospital. PATIENTS: One hundred twenty-two patients with Serratia bacteremia
      between January 1991 and June 2001. METHODS: Infectious disease physicians
      collected data from medical records regarding patient demographics, underlying
      disease or condition, portal of entry, microorganism, antibiogram, complications,
      antibiotics received, and outcome. RESULTS: Among 122 Serratia isolates, 117
      (95.9%) were Serratia marcescens and 110 (90.2%) were of nosocomial origin.
      During the study period, the 122 isolates showed a high rate of resistance to
      third-generation cephalosporins (45.9%) and extended-spectrum penicillins
      (56.6%). The resistance rate to ciprofloxacin was 32.0%. The resistance rate to
      third-generation cephalosporins increased from 31.7% for 1991 to 1995 to 54.9%
      for 1996 to 1998 and 50.0% for 1999 to 2001. In the multivariate analysis, prior
      use of a second-generation cephalosporin (adjusted odds ratio [OR], 5.90; 95%
      confidence interval [CI90], 1.41 to 24.6; P = .015) or a third-generation
      cephalosporin (OR, 3.26; CI95, 1.20 to 8.87; P = .020) was a strong independent
      risk factor for resistance to third-generation cephalosporins. The overall case
      fatality rate was 25.4% (Serratia bacteremia-related case-fatality rate, 13.1%).
      CONCLUSION: Prior use of a second- or third-generation cephalosporin was the most
      important risk factor for bacteremia with Serratia resistant to third-generation
      cephalosporins, suggesting the need for antibiotic control. The potential role of
      patient-to-patient spread could not be fully evaluated in this retrospective
      study.

PMID- 12517018
TI  - Prevention of bloodstream infections with central venous catheters treated with
      anti-infective agents depends on catheter type and insertion time: evidence from
      a meta-analysis.
AB  - OBJECTIVE: To test the evidence that the risk of infection related to central
      venous catheters (CVCs) is decreased by anti-infective coating or cuffing.
      DESIGN: Systematic review of randomized, controlled trials comparing anti
      infective with inactive (control) CVCs. INTERVENTIONS: Average insertion times
      were taken as a measurement of the length of insertion. Dichotomous data were
      combined using a fixed effect model and expressed as odds ratio (OR) with 95%
      confidence interval (CI95). RESULTS: Two trials on antibiotic coating (343 CVCs)
      had an average insertion time of 6 days; the risk of BSI decreased from 5.1% with
      control to 0% with anti-infective catheters. There were no trials with longer
      average insertion times. In three trials on silver collagen cuffs (422 CVCs), the
      average insertion time ranged from 5 to 8.2 days (median, 7 days); the risk of
      BSI was 5.6% with control and 3.2% with anti-infective catheters. In another
      trial on silver collagen cuffs (101 CVCs), the average insertion time was 38
      days; the risk of BSI was 3.7% with control and 4.3% with anti-infective
      catheters. In five trials on chlorhexidine-silver sulfadiazine coating (1,269
      CVCs), the average insertion time ranged from 5.2 to 7.5 days (median, 6 days);
      the risk of BSI decreased from 4.1% with control to 1.9% with anti-infective
      catheters. In five additional trials on chlorhexidine-silver sulfadiazine coating
      (1,544 CVCs), the average insertion time ranged from 7.8 to 20 days (median, 12
      days); the risk of BSI was 4.5% with control and 4.2% with anti-infective
      catheters. CONCLUSIONS: Antibiotic and chlorhexidine-silver sulfadiazine coatings
      are anti-infective for short (approximately 1 week) insertion times. For longer
      insertion times, there are no data on antibiotic coating, and there is evidence
      of lack of effect for chlorhexidine-silver sulfadiazine coating. For silver
      impregnated collagen cuffs, there is evidence of lack of effect for both short-
      and long-term insertion.

PMID- 12517019
TI  - Central venous catheter-related infection: a prospective, observational study to
      assess the incidence rate at a teaching hospital in Argentina.
AB  - One hundred fifty-one central venous catheters (CVCs) were observed for
      development of infection. The infection rate was higher for CVCs with a duration
      of less than 6 days than for those with a longer duration. Our data suggest that
      scheduled replacement of CVCs is not necessary.

PMID- 12517020
TI  - Guidelines for the prevention of intravascular catheter-related infections.
AB  - BACKGROUND: Although many catheter-related bloodstream infections (CRBSIs) are
      preventable, measures to reduce these infections are not uniformly implemented.
      OBJECTIVE: To update an existing evidenced-based guideline that promotes
      strategies to prevent CRBSIs. DATA SOURCES: The MEDLINE database, conference
      proceedings, and bibliographies of review articles and book chapters were
      searched for relevant articles. STUDIES INCLUDED: Laboratory-based studies,
      controlled clinical trials, prospective interventional trials, and epidemiologic
      investigations. OUTCOME MEASURES: Reduction in CRBSI, catheter colonization, or
      catheter-related infection. SYNTHESIS: The recommended preventive strategies with
      the strongest supportive evidence are education and training of healthcare
      providers who insert and maintain catheters; maximal sterile barrier precautions
      during central venous catheter insertion; use of a 2% chlorhexidine preparation
      for skin antisepsis; no routine replacement of central venous catheters for
      prevention of infection; and use of antiseptic/antibiotic-impregnated short-term
      central venous catheters if the rate of infection is high despite adherence to
      other strategies (ie, education and training, maximal sterile barrier
      precautions, and 2% chlorhexidine for skin antisepsis). CONCLUSION: Successful
      implementation of these evidence-based interventions can reduce the risk for
      serious catheter-related infection.

PMID- 12517021
TI  - ECG of the month. Intermittently wide QRS complexes. Sinus rhythm with Wolff
      Parkinson-White type pre-excitation and spontaneous intermittent block in the
      accessory pathway.

PMID- 12517022
TI  - Radiology case of the month. Sclerotic bone disease in an 8-year-old dwarf.
      Pycnodysostosis.

PMID- 12517023
TI  - Pathology case of the month. Abdominal pain and weight loss in a young adult.
      Anaplastic large cell lymphoma.
AB  - A 34-year-old black man presented with a three-month history of abdominal pain,
      anorexia, and weight loss. Physical examination and radiologic studies revealed
      diffuse lymphadenopathy. Ascites and bilateral pleural effusions were also
      evident. The patient's condition deteriorated after admission, and he died prior
      to initiation of therapy. Histologic sections and special studies performed on a
      cervical lymph node biopsy performed shortly before the patient's death are shown
      in Figures 1-4. A bone marrow aspirate and biopsy were also performed and
      revealed no evidence of disease.

PMID- 12517024
TI  - Clinical case of the month. Severe progressive weakness in a 58-year-old man.
      Myasthenia gravis.
AB  - Myasthenia gravis historically has been associated with significant morbidity and
      mortality rates, and most of those afflicted either died of the disease or became
      greatly disabled. However, modern understanding of the pathogenesis of this
      disorder has led to several effective treatments which have transformed the
      prognosis of this disease greatly.

PMID- 12517025
TI  - Congenitally bicuspid aortic valves in adults.
AB  - The congenitally bicuspid aortic valve occurs in more than 1% of the population.
      Although it may never cause difficulty and first be discovered at autopsy, more
      often it results in some hemodynamic abnormality. Its clinical manifestations are
      varied, and its early recognition is essential if we are to prevent the dreaded
      complication of infective endocarditis.

PMID- 12517026
TI  - St. Louis encephalitis outbreak in Louisiana in 2001.
AB  - A description of the St. Louis encephalitis (SLE) outbreak in Northeast Louisiana
      is presented. In the fall of 2001 there were 63 cases of St. Louis encephalitis
      in Monroe and West Monroe and seven additional cases in the neighboring parishes
      of Richland, Morehouse and Franklin. All cases had a clinical presentation of
      encephalitis and were confirmed serologically. Clinically most cases presented
      with fever, meningitis syndrome with altered mental status. Tremors were common
      (56% of cases). There were three deaths. Age-group distribution showed a
      predominance among 45 and older. The epidemic curve based on diagnosis date
      showed an explosive outbreak starting August 8, 2001, reaching a peak by the
      second week, and progressively slowing down. The curve showed that by the time
      the first case was diagnosed, 60% or more of the cases were already infected.
      Most of the cases come from low socio-economic areas. Houses were often run down,
      many with screens in disrepair. Backyards were usually large, with heavy brush
      and many trees. There was an abundance of sources of mosquito larvae,
      particularly for Culex quinquefasciatus which is the main vector. Mosquito pools
      confirmed the presence of SLE virus. As soon as the first case was reported, a
      campaign of health education and increased mosquito adulticiding were
      implemented.

PMID- 12517027
TI  - Myxosarcoma: a rare primary cardiac tumor.
AB  - We describe the case of a patient with myxosarcoma of the left ventricle, a very
      rare type of primary cardiac sarcoma, who presented with features of acute
      pericarditis and discuss the management of this condition.

PMID- 12517028
TI  - Coronary-calcium screening to improve risk stratification in primary prevention.
AB  - Coronary artery disease is very prevalent in the United States where over 7
      million people suffer from it, and more than 500,000 die from its complications
      annually. For the majority of individuals suffering an acute myocardial
      infarction, the event represents the first indication of the presence of
      underlying coronary atherosclerosis. Furthermore, due to the outward remodeling
      of arteries that slowly accumulate atheroma in their imtima (Glagov effect),
      sudden death or acute myocardial infarction may occur in the absence of
      obstructive luminal atherosclerotic plaque. Therefore, it might seem highly
      desirable to detect atherosclerosis in its early stages to implement effective
      preventive measures rather than apply delayed treatment. Yet, statistics from
      primary care and sub-specialty practices indicate that the preventive attitude of
      the majority of physicians is not sufficiently developed, and most training
      programs still struggle to implement strong educational curricula in this field.
      To these limitations, one may add that traditional risk factors help predict only
      about 60% to 65% of the risk, while many individuals continue to suffer events in
      the absence of established risk factors for atherosclerosis. In light of this
      knowledge, several tools have been developed to identify atherosclerotic disease
      in its pre-clinical stages in the hope of modifying its natural history. This
      review deals with the utilization of electron beam tomography for detection of
      coronary arterial calcium as an additional tool to risk stratify asymptomatic
      individuals.

PMID- 12517029
TI  - Hospital ethics committees: formation, function, and case consultation.
AB  - The objective of this paper is to present the concept of hospital ethics
      committees (HEC) with the hope of expanding awareness, knowledge, and use of such
      entities. HECs typically serve three functions--education, development of
      hospital policy, and ethical case consultation. In the last role, HECs aim to
      assist healthcare professionals and their patients achieve mutually acceptable
      decisions when dilemmas about care arise. The theory and practical methodology
      used by an HEC when processing a case are detailed. It is expected that a greater
      awareness of the functions and construction of an HEC will expand use of this
      service by health professionals and ultimately enhance patient care.

PMID- 12517030
TI  - A call to leadership.

PMID- 12517031
TI  - Basic ethical principles in European bioethics and biolaw: autonomy, dignity,
      integrity and vulnerability--towards a foundation of bioethics and biolaw.
AB  - This article summarizes some of the results of the BIOMED II project "Basic
      Ethical Principles in European Bioethics and Biolaw" (1995-1998) connected to a
      research project of the Danish Research Councils "Bioethics and Law" (1993-1998).
      The BIOMED project was based on cooperation between 22 partners in most EU
      countries. The aim of the project was to identify the ethical principles of
      respect for autonomy, dignity, integrity and vulnerability as four important
      ideas or values for a European bioethics and biolaw. The research concluded that
      the basic ethical principles cannot be understood as universal everlasting ideas
      or transcendental truths but they rather function reflective guidelines and
      important values in European culture. The method of the research was conceptual,
      philosophical analysis of the cultural background of the four values or normative
      ideas that people use and find important in their existence. Moreover, this was
      combined with analysis of empirical legal material and policy documents. Also, a
      number of qualitative interviews with relevant experts were carried out. Another
      important result of the BIOMED project was the partner's Policy Proposals to the
      European Commission, the Barcelona Declaration, unique as a philosophical and
      political agreement between experts in bioethics and biolaw from many different
      countries. The Policy Proposals are reprinted here at the end of the article.

PMID- 12517032
TI  - Humane healthcare as a theme for social ethics.
AB  - The concept of 'humane healthcare' cannot and may not be limited to a personal
      virtue. For elucidating its meaning and making it functional as a critical
      ethical criterion for healthcare as a social institution, it is necessary to
      reflect on the social, cultural, and historical conditions in which modern
      healthcare finds its offspring and its further development. Doing this is the
      object and aim of social ethics. Social ethics in itself covers a broad area of
      different approaches. A main division can be made between a liberal and a
      communitarian approach. This article focuses on the latter and concentrates on
      one of its representatives, Charles Taylor. The paper starts with two clarifying
      paragraphs: one about the terms humane and human, a second about the scope of
      social ethics. Next, because the term humane presupposes a certain view of man,
      attention will be paid to the lack of consensus in this respect within modernity,
      using some reflections of Taylor. In his view, resigning in this lack is a threat
      for one of the main motives behind modernity: the pursuit of a good and
      meaningful life. In the following section Taylor's analysis is applied to
      contemporary healthcare, by means of two examples. At the end the question is
      raised how to promote humane healthcare? In a short and conclusive sketch, three
      suggestions are offered for further research: scrutiny of goals and meanings
      within healthcare and culture, the broadening of the concept of autonomy and the
      upholding of human dignity as an intrinsic and imperative value.

PMID- 12517033
TI  - The impact of factitious disorder on the physician-patient relationship. An
      epistemological model.
AB  - Theoretical models for physician-patient communication in clinical practice are
      described in literature, but none of them seems adequate for solving the
      communication problem in clinical practice that emerges in case of factitious
      disorder. Theoretical models generally imply open communication and respect for
      the autonomy of the patient. In factitious disorder, the physician is confronted
      by lies and (self)destructive behaviour of the patient, who in one way or another
      tries to involve the physician in this behaviour. It is no longer controversial
      that the physician should communicate his consideration of a factitious disorder
      without insistence that the patient accepts this diagnosis. However, the balance
      between patient autonomy and open communication on the one hand, and the
      preservation of the patient's health, physician integrity and of a constructive
      physician-patient relationship on the other is easily disrupted. In this article,
      an epistemological model is described to facilitate a positive outcome of
      confrontation in treatment of factitious disorder. Analysing the problem in terms
      of systems theory will help the physician to assess what information is
      appropriate to use in which phase of the patient's treatment, while preserving
      the physician-patient relationship.

PMID- 12517034
TI  - Development of sensitivity to the needs and suffering of a sick person in
      students of medicine and dentistry.
AB  - Doctor and patient meet in a circle of feelings determined by suffering.
      Sensitivity to the suffering is an axis determining the nature of the doctor and
      patient relationship. The patient's experience of an illness is individual,
      private, and very often difficult to describe. But the possibility to understand
      the suffering of another person comes from the fact that suffering is a universal
      feeling. We propose to enter the world of patient's experience by writing a
      letter to a doctor, which would reflect their experiences and expectations
      towards him. This was the task required for 120 students of the second year of
      medicine and dentistry education.

PMID- 12517036
TI  - Wisdom, casuistry, and the goal of reproductive counseling.
AB  - Reproductive counseling includes counseling of prospective parents by
      obstetricians, clinical geneticists, and genetic counselors regarding, for
      example, the use of assisted reproductive technologies, prenatal testing, and
      preimplantation genetic diagnosis. Two different views on wisdom and the goal of
      reproductive counseling are analyzed. According to the first view, the goal of
      reproductive counseling is to help prospective parents reach a wise decision. A
      specific course of action is recommended by the counselor in contrast to other
      possible alternatives. According to the second view, the goal of reproductive
      counseling is not to help prospective parents reach a wise decision but to help
      them reach their own decision wisely. It is the prospective parents who should
      make the decision, and it is their value commitments that should be decisive. It
      is argued that the second approach is to be preferred to the first. It combines
      respect for autonomy with a recognition of the need for assistance in decision
      making. Both the first and second views relate the goal of reproductive
      counseling to wisdom. A problem is, however, what wisdom more precisely means -
      there are many different views. A casuistic view of wisdom is investigated. This
      view roughly defines wisdom as practical prudence in dealing with particular
      cases. What characterizes a casuistic decision-making method is elaborated in
      more detail. Applied to the second view, a casuistic view of wisdom implies that
      the counselor should encourage prospective parents to take into consideration the
      nature of the particular problem at hand, the context of the problem, their own
      individual identities, their personal value commitments, and various alternative
      perspectives, values and arguments.

PMID- 12517035
TI  - Whither our art? Clinical wisdom and evidence-based medicine.
AB  - The relationship between evidence-based medicine (EBM) and clinical judgement is
      the subject of conceptual and practical dispute. For example, EBM and clinical
      guidelines are seen to increasingly dominate medical decision-making at the
      expense of other, human elements, and to threaten the art of medicine. Clinical
      wisdom always remains open to question. We want to know why particular beliefs
      are held, and the epistemological status of claims based in wisdom or experience.
      The paper critically appraises a number of claims and distinctions, and attempts
      to clarify the connections between EBM, clinical experience and judgement, and
      the objective and evaluative categories of medicine. I conclude that to demystify
      clinical wisdom is not to devalue it. EBM ought not be conceived as needing to be
      limited or balanced by clinical wisdom, since if its language is translatable
      into terms comprehensible and applicable to individuals, it helps constitute
      clinical wisdom. Failure to appreciate this constitutive relation will help
      perpetuate medical paternalism and delay the adoption of properly evidence-based
      practice, which would be both unethical and unwise.

PMID- 12517037
TI  - Incomprehensibility: the role of the concept in DSM-IV definition of
      schizophrenic delusions.
AB  - In this paper the role of incomprehensibility in the conceptualization of the DSM
      IV definition of delusion is discussed. According to the analysis, the conceptual
      dependence of DSM-IV definition of delusion on "incomprehensibility" is
      manifested in several ways and infested with ambiguity. Definition of "bizarre"
      delusions is contradictory and gives room for two incompatible readings. Also the
      definition of delusion manifests internal inconsistencies and its tendency to
      account for delusions in terms of misinterpretation is bound to miss the content
      of the traditional comprehension of delusionality. It is suggested that the
      ambiguities in defining delusions has to do with the question whether psychiatric
      practice is better accounted for in terms of the grammar of "incorrectness" or of
      "incomprehensibility".

PMID- 12517038
TI  - (Mis)understanding Singer: replaceability of children or intellectual endeavour?
AB  - Should doctors have the possibility to save children from incurable suffering and
      end their lives?. At first glance, the standpoints in the debate around this
      question seem translucent and well known and the debate intelligible. I contend
      that this is not the case and I will illustrate this in analysing the debate
      between Peter Singer and Ulrich Bleidick. Whomever wants to answer the question
      whether it is acceptable to end the lives of suffering small children will have
      to do some careful reading and thinking about the different and differing moral
      arguments in the debate. This demands emotional restraint and intellectual
      honesty. Trying to understand Singer and his opponents is a challenging way of
      charting what exactly is at stake in this debate.

PMID- 12517039
TI  - Learning outcomes in health care ethics; a case study concerning one course.

PMID- 12517040
TI  - Relation between antibody against oxidized low-density lipoprotein and extent of
      coronary atherosclerosis.
AB  - BACKGROUND AND PURPOSE: The role of antibody against oxidized low-density
      lipoprotein (Ab-ox-LDL) in acute myocardial infarction (AMI) and coronary artery
      disease (CAD) has not been fully elucidated. This study investigated the
      relationship between Ab-ox-LDL titers and the extent of coronary atherosclerosis,
      and determined the clinical significance of this antibody in AMI. METHODS: A
      total of 70 patients with significant coronary atherosclerosis demonstrated by
      coronary angiography were recruited. These patients were divided into AMI (n =
      33; mean age, 63 yr; 29 men) and chronic stable CAD (n = 37; mean age, 62 yr; 30
      men) groups. Serum Ab-ox-LDL was measured using an enzyme-linked immunosorbent
      assay. The extent of coronary atherosclerosis was assessed by an angiographic
      diffuse score system. RESULTS: In all patients, Ab-ox-LDL was significantly
      correlated with white blood cell count (r = 0.309; p = 0.009), but not with lipid
      profile or the diffuse score. Ab-ox-LDL (422.0 +/- 60.4 vs. 263.8 +/- 30.2 U/L; p
      = 0.018), white blood cell count (9,742 +/- 457 vs. 7,211 +/- 327/mm3; p <
      0.001), and C-reactive protein (10.5 +/- 3.1 vs. 2.9 +/- 0.5 mg/L; p = 0.022)
      were significantly higher in patients with AMI than in those with chronic CAD.
      Peak creatine kinase concentration was significantly correlated with Ab-ox-LDL (r
      = 0.499; p = 0.003) among patients with AMI. CONCLUSION: Ab-ox-LDL is higher in
      patients with AMI and is correlated with myocardial damage to a greater degree
      than with the severity of coronary atherosclerosis and lipid profiles.

PMID- 12517041
TI  - Colorectal cancer screening in asymptomaic adults: comparison of colonoscopy,
      sigmoidoscopy and fecal occult blood tests.
AB  - BACKGROUND AND PURPOSE: Fecal occult blood tests (FOBT) and flexible
      sigmoidoscopy have previously been recommended for colon cancer screening. More
      recently, studies have recommended colonoscopy due to the high rates of advanced
      neoplasm not detected by FOBT and sigmoidoscopy. Previous studies of the
      effectiveness of colonoscopic screening in Taiwan were limited to families of
      patients with colorectal cancer. This study compared colonoscopy, sigmoidoscopy
      and FOBT for colorectal cancer screening in asymptomatic adults. METHODS:
      Screening colonoscopies and FOBT were performed in asymptomatic adults enrolled
      in our health-screening program between January 1997 and December 2000. Advanced
      neoplasm was defined as the presence of a polyp larger than 1 cm, polyps with
      villous or severe dysplastic features, or cancer. The junction of the splenic
      flexure and descending colon was defined as the boundary of the proximal and
      distal colon, and it was presumed that the distal colon would be examined using
      sigmoidoscopy in all patients. Data on the prevalence of polyps, advanced
      neoplasm, and cancer among different age groups were obtained. The results of
      chemical and immunologic FOBT were compared. The anatomic distributions of
      advanced neoplasm and cancer were analyzed. RESULTS: A total of 7,411
      colonoscopic examinations were included in the analysis. Advanced neoplasms were
      present in 93 examinations (1.3%), including 16 cancers (0.2%). Chemical FOBT
      detected 20.2% of advanced neoplasms and 37.5% of cancers. Immunologic FOBT
      detected 48.3% of advanced neoplasms and 87.5% of cancers. If sigmoidoscopy had
      been performed in place of colonoscopy, 26.9% of advanced neoplasms and 12.5% of
      cancers would not have been detected. CONCLUSIONS: Colonoscopy can detect
      neoplastic lesions undetectable by FOBT and sigmoidoscopy in asymptomatic
      subjects. These results suggest that colonoscopy should be the method of choice
      in colon cancer screening.

PMID- 12517042
TI  - Neonatal screening for congenital adrenal hyperplasia in Taiwan: a pilot study.
AB  - BACKGROUND AND PURPOSE: Congenital adrenal hyperplasia (CAH) is an autosomal
      recessive disorder with defects in steroidogenesis. Its wide and non-specific
      clinical spectrum poses problems for early diagnosis. Without a screening
      program, affected newborns may be missed, even though they have a life
      threatening illness. The purpose of this study was to survey the prevalence and
      phenotype of CAH in Taiwan by neonatal screening. METHODS: From March 1, 2000, to
      August 31, 2001, 192,687 capillary blood spots were collected nationwide. Enzyme
      linked immunosorbent assay (ELISA) was used to quantitatively measure 17
      hydroxyprogesterone (17-OHP) in all specimens. RESULTS: Thirteen cases of CAH (7
      female and 6 male) were detected, resulting in an estimated prevalence of
      1:14,822. Nine patients (69%) had salt-wasting CAH and four (31%) had simple
      virilizing CAH. All cases were identified before clinical diagnosis, and also
      before the development of adrenal crisis. CONCLUSION: This study estimated that
      20 babies with CAH are born each year in Taiwan. A nationwide neonatal screening
      program is the only way to provide early diagnosis and prompt treatment. This
      would save lives and enhance the health of affected infants.

PMID- 12517043
TI  - The nonadrenergic noncholinergic system can modulate the effect of prokinetic
      agents on contractile response of isolated guinea-pig trachea segments to
      electrical field stimulation.
AB  - BACKGROUND AND PURPOSE: Prokinetic agents are frequently used in patients with
      bronchopulmonary dysplasia for the treatment of gastroesophageal reflux, but the
      effects of these agents on the airway remain unclear. This study investigated
      factors mediating the effects of two prokinetic agents, metoclopramide and
      cisapride, on contractile response to electrical field stimulation (EFS) in
      guinea-pig trachea segments. METHODS: Trachea segments from male Dunkin-Hartley
      guinea pigs were used. Concentration-response curves of metoclopramide and
      cisapride to electrical stimulus of 50 V at 20 Hz were obtained as baseline
      values. A second concentration-response curve to each prokinetic drug was
      obtained after preincubation with 300 microM N(G)-nitro-L-arginine-methyl ester
      (L-NAME, a nitric oxide synthetase inhibitor) and 2 U/mL alpha-chymotrypsin (a
      vasoactive intestinal peptide inhibitor). Parallel control studies were
      undertaken to correct for changes in the sensitivity of the tissue to EFS.
      RESULTS: At lower concentrations (< or = 1 microM), metoclopramide reduced the
      contractile response to EFS, but cisapride did not have a significant effect. At
      concentrations greater than 1 microM, metoclopramide enhanced and cisapride
      suppressed the airway smooth muscle contraction evoked by EFS. However, when
      inhibitory nonadrenergic noncholinergic (NANC) innervations were
      pharmacologically abolished by L-NAME and alpha-chymotrypsin, cisapride caused
      augmentation and metoclopramide did not have a significant effect on the
      contractile response to EFS at concentrations of 1 microM or less. CONCLUSION:
      This study demonstrated that the effect of metoclopramide and cisapride on the
      contractile response to EFS can be influenced by inhibitory NANC innervations in
      guinea-pig trachea.

PMID- 12517044
TI  - Response to influenza vaccine in children with leukemia undergoing chemotherapy.
AB  - BACKGROUND AND PURPOSE: To assess the ability of children with acute
      lymphoblastic leukemia (ALL) to develop an antibody response after influenza
      vaccination. METHODS: A total of 65 children under 15 years old were studied,
      including 25 children with ALL undergoing chemotherapy, 30 with asthma in
      remission who were regularly followed at clinics, and 10 healthy children. The
      influenza vaccine contained antigens B/Yamanashi/166/98, A/New Caledonia/20/99
      (H1N1), and A/Panama/2007/99 (H3N2). RESULTS: Children with ALL developed
      significant antibody titers to A/Panama /2007/ 99 antigen 4 weeks after the
      second immunization. Seroconversion rates after two doses of vaccine were 57.1 to
      84.6% and seroresponse rates were between 24 and 60% in children with ALL.
      Compared to children with asthma in remission, who were regarded as
      immunocompetent individuals, the ALL children had less seroconversion and lower
      seroresponse rates to A/New Caledonia/20/99 (H1N1). The seroconversion and
      seroresponse rates to B/Yamanashi/166/98 and A/ Panama/2007/99(H3N2) antigens
      were comparable in asthmatic and leukemic children. On the other hand, the
      antibody response in children with ALL who received reinduction chemotherapy
      suggests that the therapy did not impair seroresponse rates. CONCLUSION: Our data
      suggest that the influenza vaccine is safe and effective in children with either
      ALL or asthma in Taiwan.

PMID- 12517045
TI  - Psychobehavioral response and weight loss prediction in a hospital-based weight
      reduction program.
AB  - BACKGROUND AND PURPOSE: Depression and binge eating are common adverse
      psychologic responses associated with weight loss in overweight and obese adults.
      This study aimed to assess the effects of different degrees of weight loss on
      psychologic functioning and the relationship between mood change and weight
      reduction, and to identify predictors of short-term weight loss among subjects in
      a hospital-based weight reduction program. METHODS: A total of 189 obese subjects
      who participated in a hospital-based weight-reduction program during a 12-week
      interval were enrolled in this study. They ranged in age from 18 to 67 years
      (mean, 40.5 +/- 12.3 yr) with female predominance (87.8%). Mean body weight was
      79.3 +/- 13.9 kg and mean body mass index was 31.1 +/- 3.8 kg/m2 on entry into
      the program. Body weight was periodically measured and subjects were asked to
      complete two self-administered questionnaires including the Brief Symptom Rating
      Scale (BSRS) and the Bulimic Investigatory Test, Edinburgh (BITE), pre- and post
      treatment. RESULTS: Using the last observation carried forward method of
      analysis, the average weight loss for all participants was 5.6 +/- 3.7 kg. For
      subjects who completed the 12-week program, weight loss was 6.6 +/- 3.6 kg.
      Subjects who completed the program (n = 115, 60.8%) had significantly reduced
      BITE as well as all BSRS subscale scores at the end of the program. There was no
      linear relationship between mood change and weight loss by correlation analysis,
      but subjects with higher degrees of weight loss had improvement in more
      dimensions of psychologic functioning. Initial mood and binge-eating status
      predicted neither compliance nor weight reduction. Two biologic factors (initial
      weight loss, initial body weight) and one behavioral factor (attendance rate)
      were identified as significant predictors of short-term weight loss for all
      subjects. CONCLUSIONS: There was no evidence that weight loss made mood or eating
      pathology worse among those who completed the weight loss program. Beneficial
      effects on general psychologic functioning and eating pathology were demonstrated
      for subjects with a minimal weight loss of 5% of initial weight and who completed
      the program. Psychologic assessments at the start of the program did not predict
      weight loss at the end of participation in this hospital-based weight loss
      program.

PMID- 12517046
TI  - Diffuse gastric polyposis: report of a case.
AB  - In diffuse gastric polyposis, all or a large part of the gastric mucosa is
      covered with polyps. Diffuse gastric polyposis was accidentally found in a 59
      year-old female during study of her anemia. The diagnosis was confirmed by
      esophagogastroduodenoscopy, double-contrast barium upper gastrointestinal
      roentgenography, and colonoscopy. Treatment was total gastrectomy with Roux-en-Y
      esophagojejunostomy. Differential diagnosis of inherited gastrointestinal
      polyposis syndrome should be considered; malignant potential is the greatest
      concern.

PMID- 12517047
TI  - Metastatic hepatocellular carcinoma in the nasal septum: report of a case.
AB  - Metastatic hepatocellular carcinoma (HCC) in the sinonasal region is rare. We
      report the case of a 45-year-old male hepatitis B carrier who had metastatic HCC
      2 years after resection of the primary tumor. The patient died of terminal
      hepatic failure 6 weeks after the discovery of nasal septal metastasis. The
      clinical and histopathologic characteristics of the primary and metastatic
      hepatocellular tumors are described. This is the first reported case of nasal
      septal metastasis from HCC.

PMID- 12517048
TI  - Adrenal insufficiency combined with gastric cardia ulcer due to herpes simplex
      virus type 1 infection.
AB  - Adrenal insufficiency combined with gastric ulcer due to herpes simplex virus
      (HSV) infection is a very unusual condition. A 75-year-old woman suffered from a
      4-day history of poor appetite, constipation, dysuria, severe headache,
      generalized pain and malaise. Hyponatremia was noted. Escherichia coli infection
      was identified from urine culture. Poor pituitary-adrenal axis response to
      hyponatremia and infection, as well as a history of intermittent treatment with
      steroids, led to a diagnosis of iatrogenic tertiary adrenal insufficiency. During
      hospitalization, the patient passed tarry stools. In addition to an antral ulcer,
      panendoscopy revealed an ulcer in the gastric cardia with a clean base and
      irregular margins. Biopsy of the cardia demonstrated multinucleated giant cells
      in the stratified squamous epithelium. Polymerase chain reaction studies
      confirmed HSV type 1 infection. In patients suffering from gastric cardia ulcer,
      the possibility of herpes infection must be considered, especially when
      complicated by steroid treatment or misuse. Because herpes infection in the
      squamous epithelium is self-limiting, practitioners should be aware of it, so
      that overtreatment can be avoided.

PMID- 12517049
TI  - Hereditary hemorrhagic telangiectasia mimicking metastases in a patient with
      gastric carcinoma.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is associated with arteriovenous
      malformation in multiple organs. The association of HHT with primary malignancy
      has rarely been reported. We describe the case of a 68-year-old man with gastric
      carcinoma who presented with abdominal fullness and cramping pain. Radiographic
      examination showed multiple pulmonary nodules and an osteolytic cervical spine
      lesion. The initial diagnosis of gastric cancer with multiple metastases was
      revised after meticulous imaging studies revealed these lesions to be vascular
      malformations in the lungs and vertebra. This case demonstrates that HHT may
      coexist with a primary malignancy and mimic multiple metastases.

PMID- 12517050
TI  - Smith-Magenis syndrome with bilateral vesicoureteral reflux: a case report.
AB  - Smith-Magenis syndrome (SMS) is a syndrome of multiple malformations caused by an
      interstitial deletion of chromosome 17p11.2. We report the case of an 8-year-old
      boy with SMS. Down syndrome was initially suspected in infancy based on the
      findings of generalized hypotonia, flat midface, and upslanting palpebral
      fissures. His sleep had been disturbed since infancy, and self-injurious behavior
      developed at 2 years. When he was 8 years old, these unusual neurobehavioral
      features led to suspicion of SMS, and chromosome analysis showed the 17p
      deletion, which was confirmed by fluorescence in situ hybridization of the SMS
      region. Bilateral vesicoureteral reflux, grade IV, was found at the same time,
      and he underwent bilateral ureteroplasty. The postoperative course was smooth and
      he was discharged with antibiotic prophylaxis. His sleep disturbance improved
      after treatment with melatonin. A high index of suspicion is needed for the
      timely diagnosis of SMS. Patients should be thoroughly evaluated for associated
      complications both at the time of diagnosis and at regular follow-up.

PMID- 12517051
TI  - Diverticulum of the right ventricle associated with pulmonary stenosis,
      rhabdomyoma and Wolff-Parkinson-White syndrome.
AB  - Congenital cardiac diverticulum is a rare anomaly that may present as an isolated
      lesion or in association with other malformations. Diverticulum of the left
      ventricle is more common than that of the right ventricle. We report a case of
      cardiac diverticulum over the right ventricular outflow tract and associated
      pulmonary stenosis, right atrial rhabdomyoma, and Wolff-Parkinson-White syndrome
      in a 9-month-old boy. The delta wave disappeared after removal of the atrial
      rhabdomyoma.

PMID- 12517052
TI  - Use of prophylactic antibiotics in surgery at a medical center in southern
      Taiwan.
AB  - BACKGROUND AND PURPOSE: Use of prophylactic antibiotics to prevent postoperative
      infection (POI) is a common practice in surgery. This study investigated the
      amount and cost of surgical prophylaxis in a representative general hospital in
      Taiwan in order to determine an appropriate course of action to control
      antibiotic use and decrease the burden of resistance. METHODS: The use of
      antibiotic prophylaxis for a wide variety of surgical procedures over a 6-month
      period was retrospectively evaluated in 3,104 patients at a medical center in
      southern Taiwan. RESULTS: Timing of perioperative parenteral antibiotics was
      inappropriate in 738 (23.8%) patients. The average duration of antibiotic use was
      6.4 days (2.4 days intravenous + 4.0 days oral). Only 4.9% of patients did not
      receive prophylactic antibiotics and only 9.2% received a single dose.
      Prophylaxis exceeded 1 day in 80% of patients and 3 days in 68.2%. The most
      common regimen was cefazolin plus gentamicin, used in 2,338 (75.3%) procedures.
      There were 146 POIs in 119 (3.8%) patients. The most common POI was at the
      surgical site. Aerobic gram-negative bacilli were most common among the 81
      pathogens isolated (54.3%), followed by gram-positive cocci (34.6%), anaerobes
      (8.6%) and yeasts (2.4%). The total cost for prophylactic antibiotics was New
      Taiwan (NT)$5,860,242 (approximately US$ 169,862). Had a single dose of cefazolin
      been used for all patients, the cost would have been reduced by 92.1%. Had four
      doses of cefazolin been used, the cost would have been reduced by 68.5%.
      CONCLUSIONS: This study documented the excessive use and often inappropriate
      timing of administration of antibiotics for surgical prophylaxis in a
      representative medical center in Taiwan. Strategies are needed to improve the
      appropriate use of surgical antibiotic prophylaxis in Taiwan, not only to reduce
      costs but, more importantly, to delay the emergence of resistant microorganisms.

PMID- 12517053
TI  - Sarcoidosis in Taiwan: clinical characteristics and atypical mycobacteria.
AB  - BACKGROUND AND PURPOSE: Sarcoidosis is rare in Taiwan, although increasingly more
      cases are being diagnosed. The purpose of this study was to further characterize
      the clinical features of all biopsy-proven cases of sarcoidosis diagnosed between
      1988 and 2002 in a national teaching hospital in southern Taiwan, and to detect
      mycobacterial DNA in sarcoid lesions. MATERIALS AND METHODS: A total of 28 biopsy
      proven cases of sarcoidosis were reviewed. Formalin-fixed, paraffin-embedded
      tissues were used as template for nested polymerase chain reaction (PCR)
      detection of the mycobacterial hsp65 gene. This was followed by direct DNA
      sequencing to identify the species in positive cases. RESULTS: Eleven males and
      17 females, aged 19 to 79 years (mean, 50 yr) were enrolled. Bilateral hilar
      lymphadenopathy, pulmonary lesions or both, were detected in 14 patients (50%).
      Of the 22 patients (78%) with skin involvement, nine manifested angiolupoid
      lesions on the face, a rare form of cutaneous sarcoidosis. Eight patients had
      papular lesions and five had plaque lesions, usually widespread on the
      extremities and trunk. No patients presented with erythema nodosum. Fifteen of
      the 22 patients with skin involvement had had the disease for more than 2 years.
      The hsp65 gene was detected in seven cases, four of which showed greater than 90%
      homology to four different species of atypical mycobacteria. CONCLUSION: Our
      study showed that sarcoidosis tended to affect women older than 40 years, often
      manifested angiolupoid lesions on the face, and ran a subacute to chronic course.
      Atypical mycobacteria might play a role in the etiology in a minority of our
      patients, but more cases and other potential etiologic agents need to be studied.

PMID- 12517054
TI  - Arterial response during cutting balloon angioplasty: a volumetric intravascular
      ultrasound study.
AB  - BACKGROUND AND PURPOSE: Previous studies have demonstrated that the mechanism of
      acute lumen enlargement after balloon angioplasty is a combination of vessel
      expansion and plaque redistribution, but not plaque compression. The purpose of
      this study was to clarify, from a three-dimensional aspect, the vascular response
      to cutting balloon angioplasty. METHODS: Serial intravascular ultrasound (IVUS)
      studies, including pre- and post-intervention, were performed in 36 native
      coronary lesions treated with the cutting balloon device. External elastic
      membrane (EEM), lumen, and plaque + media cross-sectional area were measured at
      16-frame intervals (30 frames = 1 mm) over a lesion length of 16 mm with the
      center on the smallest pre-intervention lumen area. Volumetric calculations were
      based on Simpson's rule. RESULTS: EEM volume (261.16 +/- 89.59 vs. 279.59 +/-
      85.92 mm3; p < 0.01) and lumen volume (106.48 +/- 37.83 v.s. 133.72 +/- 36.57
      mm3; p < 0.01) significantly increased after cutting balloon angioplasty.
      Furthermore, the plaque + media volume throughout the lesion changed
      significantly after cutting balloon angioplasty (154.68 +/- 63.36 vs. 145.87 +/-
      59.20 mm3; p < 0.01). The change in lumen volume correlated strongly with the
      change in EEM volume (r = 0.75; p < 0.01), but poorly with the change in plaque +
      media volume (r = 0.08; p = 0.64). Less longitudinal plaque redistribution was
      also observed throughout the vessel after angioplasty. CONCLUSION: The results of
      this study indicate that the predominant mechanism of lumen enlargement from
      cutting balloon angioplasty is vessel expansion, although total plaque mass
      reduction and longitudinal plaque redistribution do occur.

PMID- 12517055
TI  - Mucin gene expression in gallbladder epithelium.
AB  - BACKGROUND AND PURPOSE: The interaction of mucus, calcium and lipid is important
      in gallstone formation. The epithelium in stone-containing gallbladders has more
      mucin than in gallbladders without stones. There is altered mucin gene expression
      in black pigment stone-bearing gallbladders. In this study, we evaluated mucin
      gene expression in gallbladders containing cholesterol stones or calcium
      bilirubinate stones, and gallbladders without stones. METHODS: In situ
      hybridization with digoxigenin-tailed oligonucleotides was performed on sections
      of paraffin-embedded epithelial tissue from gallbladders with cholesterol stones
      (n = 14) or calcium bilirubinate stones (n = 12), and those without stones (n =
      10) to identify expression of MUC1, MUC2, MUC3, MUC4, MUC5B, and MUC6. RESULTS:
      The findings showed mRNA expression of MUC3, MUC5B and MUC6 in most gallbladders
      in all three groups, but stronger and extensive expression of these mRNAs in
      gallbladders with stones. MUC2 and MUC4 labeling was absent in gallbladders
      without stones, but MUC2 labeling was found in 14% and MUC4 in 50% of
      gallbladders with cholesterol stones. MUC2 expression was found in 25% and MUC4
      in 58% of gallbladders with bilirubinate stones. Increased expression of MUC1 was
      found in gallbladders with cholesterol stones (79%) and calcium bilirubinate
      stones (83%) compared to those without stones (30%). CONCLUSION: Altered mucin
      gene expression was found in gallbladders with cholesterol stones and calcium
      bilirubinate stones, as evidenced by the presence of MUC2 and MUC4 and the
      increased expression of MUC1, MUC3, MUC5B and MUC6.

PMID- 12517056
TI  - Alcohol sensitivity in Taiwanese men with different alcohol and aldehyde
      dehydrogenase genotypes.
AB  - BACKGROUND AND PURPOSE: Previous studies demonstrated that ADH2*2, encoding for
      high-maximal velocity (Vmax) beta2-alcohol dehydrogenase (ADH) activity, and
      mutant ALDH2*2, encoding for null aldehyde dehydrogenase (ALDH) 2 activity,
      independently influence susceptibility to alcoholism. A single copy of the
      ALDH2*2 allele may protect less strongly than a single copy of ADH2*2 in
      individuals carrying only one copy of either ALDH2*2 or ADH2*2. Individuals with
      various ADH2 and ALDH2 gene status may exhibit different alcohol metabolism and
      alcohol sensitivity, which affects drinking behavior. To explore the underlying
      pharmacogenetic mechanism, alcohol metabolism and alcohol sensitivity were tested
      using ethanol challenge in Taiwanese men with different ADH2 and ALDH2 genotypes.
      METHODS: Twenty-four adults, matched by age, body mass index, nutritional state,
      and homozygosity at ADH3, were recruited from a population base of 304 men. Six
      individuals were chosen with each of the different ADH2 and ALDH2 genotypes:
      ADH2*1/*1, ALDH2*1/*1; ADH2*2/*2, ALDH2*1/*1; ADH2*1/*1, ALDH2*1/*2; and
      ADH2*2/*2, ALDH2*1/*2. After a low-to-moderate challenge with ethanol (0.3 g/kg),
      blood ethanol and acetaldehyde concentrations, heart rate, and facial capillary
      blood flow (FCBF) were measured for 130 minutes. RESULTS: All heterozygous
      ALDH2*2 individuals were found to be strongly responsive to low-to-moderate
      ethanol, as evidenced by pronounced increases in heart rate and FCBF. Conversely,
      there were no significant differences in alcohol metabolism and alcohol
      sensitivity between the ADH2*2 and ADH2*1 homozygotes with identical ALDH2
      genotype. CONCLUSION: Individuals heterozygous for ALDH2*2 exhibit strong alcohol
      hypersensitivity caused by persistent accumulation of large amounts of
      acetaldehyde, but homozygosity for ADH2*2 is not dependent upon this pathway
      against alcoholism.

PMID- 12517057
TI  - Feasibility of human T-lymphotropic virus type I screening using pooled sera.
AB  - BACKGROUND AND PURPOSE: The human T-cell lymphotropic virus type I (HTLV-I)
      seroprevalence rate among volunteer blood donors in Taiwan is low. To study the
      feasibility of HTLV-I enzyme immunoassay (EIA) screening using pooled sera, we
      prospectively compared its sensitivity to that of the routine test for each
      donor. METHODS: HTLV-I EIA tests for each serum sample and a pooled-sera test
      with 50 samples from voluntary donated blood samples were performed concurrently
      to assess the effectiveness and cost savings of this screening method. RESULTS:
      Of 135,606 blood samples from volunteer donors tested for HTLV-I infection, 60
      samples (0.044%) were HTLV-I EIA-positive using the routine method. Among these,
      the positive results were confirmed by Western blot in 22 samples (36.7%). In the
      pooled-sera test, 17 of 2,713 pooled samples were EIA-positive and these results
      were all confirmed by Western blot. Five of the 22 (22.7%) EIA-positive samples
      had a false-negative result in the pooled-sera test. Serial dilution in these
      five cases revealed that the maximum dilution before loss of sensitivity was 8
      fold for two specimens and 16-fold for three specimens. CONCLUSION: In this
      study, the 50-pooled sera test had higher specificity (100%), but lower
      sensitivity (77.3%), than the routine HTLV-I screening. Our results suggest that
      use of a pooling method with five samples would leave a reasonable safety margin
      and be feasible for HTLV-I mass screening in areas with low seroprevalence for
      HTLV-I infection.

PMID- 12517058
TI  - Unplanned hospital readmission and its predictors in patients with chronic
      conditions.
AB  - BACKGROUND AND PURPOSE: Unplanned hospital readmission is a devastating
      experience for patients and is costly for society. This study determined the 60
      day unplanned readmission rate and its predicting factors in patients with
      chronic conditions. METHODS: A total of 334 patients discharged from five
      hospitals were followed for 2 months after discharge. Patients enrolled in the
      study were disabled and had a diagnosis of progressive chronic disease
      (congestive heart failure, chronic pulmonary disease, cancer) or chronic
      impairment following an acute episode (stroke, traumatic brain injury, hip
      fracture). Patients were assessed before discharge to collect in-hospital
      variables. Telephone interviews with patients and families were used to collect
      data on hospital readmission. RESULTS: Of the 334 patients followed, 76 had
      unplanned readmission (24.4%). Patients with progressive chronic disease had a
      higher readmission rate (40.9%) than those with chronic impairment following an
      acute episode (15.1%). Frailty and abnormal respiratory pattern were significant
      predictors of readmission for patients with progressive chronic disease. The
      predictors of readmission for patients with chronic impairment following an acute
      episode included frailty, clinical instability and discharge from a regional
      hospital. The major reasons for hospital readmission were exacerbation of the
      initial major disease (33/76, 43.4%) and infection (21/76, 27.7%). CONCLUSIONS:
      Exacerbation of chronic diseases and infection are the two major reasons for
      unplanned readmission. Patients with a progressive chronic disease are more
      likely to be readmitted.

PMID- 12517059
TI  - Aortico-left ventricular tunnel associated with single coronary artery in an
      infant.
AB  - Aortico-left ventricular tunnel (ALVT) is a rare congenital malformation in which
      an abnormal communication between the aorta and the left ventricle (LV) bypasses
      the aortic valve. In infants, it usually presents with congestive heart failure.
      The clinical presentations mimic aortic regurgitation or ruptured sinus of
      Valsalva aneurysm into the LV. Progressive aortic regurgitation is a common
      problem in patients with ALVT. ALVT associated with a single coronary artery is
      extremely rare. We report the case of an infant who had congestive heart failure
      caused by ALVT. The diagnosis was made by echocardiography and angiography. In
      addition, a single coronary artery from the noncoronary cusp was found during
      surgery. Congestive heart failure resolved after successful surgical repair and
      he was asymptomatic throughout 2 years of follow-up. This case illustrates that
      early diagnosis of ALVT and corrective surgery can prevent aortic valve
      incompetence and is associated with a good clinical outcome.

PMID- 12517061
TI  - Subglottic leiomyoma: report of a case.
AB  - Subglottic leiomyoma is a rare disease. We encountered such a tumor in a 7-year
      old boy who was transferred to our hospital with respiratory distress and
      hoarseness of 2 week's duration. Stridor was noted and flexible fiberoscopy
      revealed a huge mass over the subglottis. The tumor was removed endoscopically.
      Pathologic examination disclosed a leiomyoma. The patient recovered well and no
      recurrence was noted during 17 months of follow-up. Although subglottic leiomyoma
      is rare, it should be included in the differential diagnosis of a subglottic
      tumor.

PMID- 12517060
TI  - Thin-plate spline graphical analysis of the mandible in mandibular prognathism.
AB  - The chin cup has been used to treat skeletal mandibular prognathism in growing
      patients for 200 years. The pull on the orthopedic-force chin cup is oriented
      along a line from the mandibular symphysis to the mandibular condyle. Various
      levels of success have been reported with this restraining device. The vertical
      chin cup produces strong vertical compression stress on the maxillary molar
      regions when the direction of traction is 20 degrees more vertical than the chin
      condyle line. This treatment strategy may prevent relapse due to counter
      clockwise rotation of the mandible. In this report, we describe a new strategy
      for using chin-cup therapy involving thin-plate spline (TPS) analysis of lateral
      cephalometric roentgenograms to visualize transformation of the mandible. The
      actual sites of mandibular skeletal change are not detectable with conventional
      cephalometric analysis. A case of mandibular prognathism treated with a chin cup
      and a case of dental Class III malocclusion without orthodontic treatment are
      described. The case analysis illustrates that specific patterns of mandibular
      transformation are associated with Class III malocclusion with or without
      orthopedic therapy, and that visualization of these deformations is feasible
      using TPS graphical analysis.

PMID- 12517062
TI  - Liver cell adenoma with concomitant hepatocellular carcinoma: report of two
      cases.
AB  - Malignant transformation of liver cell adenoma and unequivocal hepatocellular
      carcinoma in resected liver cell adenomas are rare. We report two cases of liver
      cell adenoma with concomitant hepatocellular carcinoma. The first occurred in a
      19-year-old male with an asymptomatic liver mass and was discovered incidentally.
      He had a history of nephrotic syndrome treated with oral prednisolone for 15
      years. The second occurred in a 46-year-old female who was admitted due to right
      tubo-ovarian abscess. Computerized tomography scanning incidentally found a 10-cm
      liver mass in the right lobe. There was no history of oral contraceptive use.
      Both patients were negative for serum hepatitis B surface antigen and anti
      hepatitis C virus antibody. Neither had cirrhosis. These two cases imply that
      malignant transformation of liver cell adenoma does occur, and that liver cell
      adenomas should be excised when malignant transformation is suspected.

PMID- 12517063
TI  - Sarcoidosis in southern Taiwan.
AB  - PURPOSE: To investigate the disease characteristics of sarcoidosis in southern
      Taiwan, and to investigate diagnostic methods. METHODS: We retrospectively
      reviewed the medical records of all patients diagnosed with sarcoidosis at Chang
      Gung Memorial Hospital, Kaohsiung, from March 1988 to February 2002. RESULTS: A
      total of 12 patients (3 men, 9 women), with a mean age of 44.5 years, and a
      diagnosis of sarcoidosis by positive histology and either a typical chest
      roentgenogram or clinical presentation were included. All 12 patients had
      intrathoracic involvement (hilar or mediastinal lymph nodes, 12; lungs, 5), eight
      had skin involvement, and two had extrathoracic lymph node involvement. The most
      frequent biopsy specimens were from the skin (n = 10), followed by the
      intrathoracic lymph nodes (n = 4), lungs (n = 2), and extrathoracic lymph nodes
      (n = 2). Four patients had positive biopsies from two organs. Our data showed an
      older age distribution and a greater female predominance of the disease compared
      with Western countries. A higher rate of intrathoracic and skin involvement was
      also found, but the reason for this was not clear. CONCLUSIONS: Greater awareness
      of possible skin involvement may enable chest physicians and clinical
      practitioners to suspect this condition earlier. A histologic diagnosis from skin
      biopsy should then be made, rather than using more invasive procedures.

PMID- 12517064
TI  - Total knee arthroplasty after failed dome osteotomy.
AB  - A retrospective, clinical and radiographic analysis was done between a study
      group of 15 patients with 17 total knee arthroplasties done following failed,
      proximal-tibial dome osteotomies and a control group of 14 patients with 17
      primary arthroplasties. The groups were matched according to age of patients,
      type of prosthesis, primary disease and length of follow-up. The average length
      of follow-up was 59.4 months (range, 25-146 mo) in the study group and 62.3
      months (range, 43-140 mo) in the control group. On the basis of the knee rating
      scale of the American Knee Society, 94% of the patients had either an excellent
      or a good result in the study group. There were no significant differences in
      knee scores, function scores, or range of motion of the knee between the two
      groups during the follow-up period. Although two overcorrected valgus knees and
      one severe varus knee necessitated an autogeneic bone graft for tibial defects at
      the time of implantation of the secondary prosthesis, dome osteotomy does not
      appear to compromise a subsequent arthroplasty.

PMID- 12517065
TI  - Percutaneous retrieval of intravascular foreign bodies: experience with 19 cases.
AB  - From April 1994 to June 2002, 17 catheter fragments and two guidewires became
      intravascular foreign bodies during venous catheterization at our hospital.
      Retrievals of these 19 foreign bodies were performed percutaneously with loop
      snare techniques (10 cases), Dormia basket retrievers (eight cases) and grasping
      forceps (one case). The percutaneous retrieval procedures were successful in 18
      of 19 cases. A broken Port-A catheter fragment anchored and entrapped in the
      vascular wall of the right brachiocephalic vein failed to be removed. No
      complication was noted during or after these percutaneous procedures. Our
      experience indicates that intravascular foreign bodies can be removed easily,
      safely, and successfully with currently available percutaneous methods. As a
      result, major surgical procedures can be avoided if interventional radiologists
      are familiar with a variety of techniques for the removal of the expanding
      spectrum of intravascular foreign bodies currently encountered.

PMID- 12517066
TI  - Periodontal bone loss in Chinese subjects with untreated early-onset and adult
      periodontitis: a cross-sectional study using digital scanning radiographic image
      analysis.
AB  - The purpose of this investigation was to evaluate the differences in radiographic
      alveolar bone loss (RABL) in Taiwanese subjects with early-onset periodontitis
      (EOP) and adult periodontitis (AP) using the digital scanning radiographic image
      analysis (DSRIA). A total of 4,262 teeth from 178 individuals (96 males and 82
      females) were examined for RABL due to EOP and AP. The subjects with EOP and a
      comparison group with AP were identified from the Periodontal Clinic population
      (College of Dental Medicine, Kaohsiung Medical University). The following
      criteria were used to classify subjects with EOP and AP during the past 20 years.
      The RABL of teeth were calculated using a computer system equipped with
      Microstation 95 software, under 10 X magnification of the radiographs. Quantity
      assessment of RABL using the DSRIA showed that: (1) the means of RABL of
      maxillary and mandibular anterior teeth in the EOP group were significant greater
      than those in the AP group when the two sample t-test was used. (2) The greatest
      values of mean RABL of affected sites in the EOP group occurred most commonly in
      the first molars and mandibular incisors, whereas, in the AP group, the greatest
      values of mean RABL of affected sites occurred most commonly in the first and
      second molars. (3) Molars had the greatest mean RABL followed by incisors,
      premolars and canines. (4) The mean RABL increased with increasing age. We
      conclude that the features of naturally progressing alveolar bone loss at the
      molar and incisor sites in untreated subjects with the EOP and AP revealed that
      the mean RABL in the EOP group was faster and greater than that in the AP group.

PMID- 12517067
TI  - Comprehensive measurement for clinical dosimetry of tertiary multileaf
      collimator.
AB  - To initiate the use of a tertiary multileaf collimator (MLC) in the clinic, a set
      of dosimetry data for clinical use of the MLC, the secondary field size jaw and
      the MLC tracked by the jaw were measured. The dose calculation technique from the
      commissioned jaw field data was established. The dosimetry characteristics
      included absolute output (Dw), collimator scatter factor (Sc), total scatter
      factor (Scp), phantom scatter factor (Sp), percentage depth dose (PDD), tissue
      maximum ratio (TMR), and peak scatter factor (PSF). The absolute output of the
      MLC field was +5% to +2% greater than that of the same jaw size field from 4 x 4
      to 24 x 24 cm2 fields. The variation of Sc and Scp ranged from 4 x 4 to 24 x 24
      cm2 fields and were less than that of the jaw fields, while the Sp, PDD and TMR
      values remained the same. Importantly, when the MLC-only field was performed
      without the collimator jaws tracking close to the field segments, greater output
      was delivered, and PSFs should be used to calculate the MLC field output.

PMID- 12517068
TI  - Concurrent validity of the scale for screening of developmental delay.
AB  - This study establishes the concurrent validity of the Screening Scale of
      Developmental Delay II (SSDD-II) with the Bayley Scale of Infant Development II
      (BSID-II). Three hundred and seventy-nine children referred by pediatricians at
      the Clinic of Developmental Delay at the Kaohsiung Medical University-Medical
      Center were tested using the SSDD-II, and about 1 week to 1 month later, they
      were tested again using the BSID-II. The results indicate that (1) the SSDD-II
      score increased as age increased, fitting the principle of developmental
      sequence. (2) The raw scores of the Mental and Motor scales of the BSID-II
      significantly correlated with the five subscales of the SSDD-II. (3) The three
      facet scale scores (language, cognitive and motor) of the BSID-II also
      significantly correlated with the five subscales of the SSDD-II. The SSDD-II has
      a high concurrent validity, and is a convenient scale to use to screen children
      for developmental delay in clinical practice in Taiwan.

PMID- 12517069
TI  - Arrhythmogenic right ventricular cardiomyopathy: three cases.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare disease
      characterized by replacement of myocardium with fibrofatty tissue. It mainly
      involves the right ventricle (RV) and causes abnormal RV performance. ARVC is the
      most common cause of sudden cardiac death in young Italian athletes because it
      induces malignant ventricular tachyarrhythmias. Clinical manifestations of ARVC
      may be different between Chinese and Western patients. In this paper, we share
      our experience of the clinical manifestations of ARVC and review previous reports
      of ARVC.

PMID- 12517070
TI  - Tc-99m di-isopropyl-iminodiacetic acid cholescintigraphic findings in Rotor's
      syndrome.
AB  - A 10-year-old girl with Rotor's syndrome was studied using Tc-99m di-isopropyl
      iminodiacetic acid cholescintigraphy. The findings showed slow hepatic uptake,
      persistent cardiac blood pool radioactivity, and prominent renal excretion. The
      contribution of cholescintigraphy and pathophysiology will be discussed via a
      literature review.

PMID- 12517071
TI  - Langerhans cell histiocytosis of bone--a case report.
AB  - Langerhans cell histiocytosis of bone causes bone destruction and frequent bone
      reactions that mimic benign and malignant neoplasms as well as osteomyelitis. The
      bony lesion of Langerhans cell histiocytosis consists of histiocytes with
      variable numbers of eosinophils, lymphocytes, and neutrophils. We present a rare
      case of Langerhans cell histiocytosis of bone, including imaging studies and
      pathology. In addition, we discuss the classification and pathology of Langerhans
      cell histiocytosis.

PMID- 12517072
TI  - Cloning, characterization, and expression studies in Escherichia coli of growth
      hormone cDNAs from Indian zebu cattle, reverine buffalo, and beetal goat.
AB  - The growth hormone cDNAs from three different economically important animal
      species of indian origin viz., indian zebu cattle (Bos indicus), indian reverine
      buffalo (Bubalus bubalis), and beetal goat (Capra hircus) were isolated by the RT
      PCR technique. The amplified product was then cloned into phagemid
      pBluescriptIIKS- and the nucleotide sequence of the entire 573 base coding region
      for each product was determined. The genetic sequences as well as the translated
      protein sequence of these ruminant species were compared to that of closely
      related species like taurine cattle (Bos taurus) and sheep (Ovis aries). A very
      high degree of nucleotide sequence homology, ranging between 97-98%, was
      observed. Subsequently, the buffalo and goat cDNAs were used for expression
      studies in Escherichia coli. Very low levels of expression resulted when the
      growth hormone cDNAs were directly placed under the strong E. coli (trc) or phage
      (T7) promoters with the approximate level being less than 0.1% and 1% of the
      intracellular E. coli proteins, respectively. The nearly 10-fold enhancement of
      the level of expression as observed was attributable to the nature of the
      untranslated leader sequence donated by the individual expression element. High
      level (about 20% of soluble E. coli protein) expression of buffalo/goat growth
      hormone was achieved as a fusion protein with glutathione-s-transferase (GST) in
      pGEX-KT. Further, although attempts at converting the GST-GH fusion protein
      system to a two-cistronic gene expression system were unsuccessful, the
      utilization of a short synthetic first cistron in the two-cistronic mode of
      expression resulted in high levels (approximately 30% of soluble protein cell
      fraction) of GH polypeptide with a native N-terminus in E. coli for all three
      cDNAs.

PMID- 12517073
TI  - Development of 47 new microsatellite markers from a BTA6 library.
AB  - Chromosome-specific libraries provide a means to isolate genetic markers from
      specific chromosomal regions. A small-insert BTA6 library, constructed by
      microdissection, was screened for dinucleotide repeats (CA)15 and (GA)15. A total
      of 47 new microsatellite loci were developed and tested for polymorphism and
      informativeness using the MARC bovine mapping family.

PMID- 12517074
TI  - FHF-2 in the turkey (Meleagris gallopavo).
AB  - A cDNA clone homologous to the fibroblast growth factor homologous factor (FHF-2)
      was isolated and sequenced from the turkey (Meleagris gallopavo). The DNA
      sequence of the turkey was almost identical to that of the chicken (99%
      similarity) differing at only 8 of 770 nucleotides in the coding region resulting
      in a single amino acid difference between these poultry species. The 3'UTR of the
      turkey FHF-2 gene was 445 nucleotides in length and included an imperfect CT
      microsatellite (ms) repeat. The sequence of the 3'UTR was amplified from genomic
      DNA of the chicken and found to be highly conserved differing at only three
      nucleotides when compared to the turkey. Length of the CT repeat was indifferent
      in a sample of 52 turkeys (monomorphic) however, the number of CT repeats was
      greater in the turkey than in the chicken. No inter-individual polymorphism was
      detected in multiple sequences of the 3'UTR of the FHF-2 gene in the turkey.
      Based on comparison of the turkey and chicken sequences, the mutation rate for
      coding and associated non-coding (3'UTR) regions of FHF-2 are approximately
      equal.

PMID- 12517076
TI  - PCR multiplexed microsatellite panels to expedite canine genetic disease linkage
      analysis.
AB  - Modern dog breeds possess large numbers of genetic diseases for which there are
      currently few candidate genes or diagnostic tests. Linkage of a microsatellite
      marker to a disease phenotype is often the only available tool to aid in the
      development of screening tests for disease carriers. Detection of linkage to a
      specific disease phenotype requires screening of large numbers of markers across
      known affected and unaffected animals. To establish high throughput genome
      scanning this study placed 100 canine microsatellite markers, arranged by
      fragment size and fluorescent dye label, into 12 PCR multiplexed panels. The
      highest degree of multiplexing was 11 markers per panel while the lowest was five
      markers per panel; each panel was run in one gel lane on automated DNA
      sequencers. Selection of the markers was based upon chromosomal or linkage group
      locations, degree of polymorphism, PCR multiplex compatibility and ease of
      interpretation. The marker set has an average spacing of 22.25 centiMorgan (cM).
      Marker polymorphism was evaluated across 28 American Kennel Club (AKC) recognized
      breeds. The utility of buccal swab vs. blood samples was also validated in this
      study as all template DNA was derived from swabs obtained and submitted by
      participating dog breeders and owners. The PCR multiplexed microsatellite panels
      and sampling method described in this report will provide investigators with a
      cost effective and expedient means of pursuing linkage studies of specific canine
      genetic diseases.

PMID- 12517077
TI  - Words, dictionaries, poems, and pictures.

PMID- 12517078
TI  - Decision making for severely brain-injured newborns.

PMID- 12517079
TI  - Commentary: Biological worth does not equate with moral worth.

PMID- 12517080
TI  - Commentary: Humanity and personhood.

PMID- 12517081
TI  - Regulating research involving adults who lack decision making capacity.

PMID- 12517075
TI  - Generation of expressed sequence tags from a normalized porcine skeletal muscle
      cDNA library.
AB  - Recent developments in microarray technologies permit scientists to analyze
      expression of thousands of genes simultaneously in diverse biological systems. In
      an effort to provide integrated resources for application of microarray
      technologies to studies of skeletal muscle growth and development in swine, we
      have constructed a normalized cDNA library from porcine skeletal muscle. The
      effectiveness of normalization was evaluated by DNA sequencing of clones randomly
      picked from the library before and after normalization, and also by Southern blot
      hybridization using probes representing abundant transcripts. Our data suggests
      that the normalization procedure successfully reduced the highly abundant cDNA
      species in the normalized library. To date, a total of 782 EST (expressed
      sequence tag) sequences have been generated from this normalized library (687
      ESTs) and the original library (95 ESTs). The sequence information of these ESTs
      plus their BLAST results has been made available through a web accessible
      database (http://nbfgc.msu.edu). Cluster analysis of the data indicates that a
      total of 742 unique sequences are present in this collection. BLASTN search of
      the 742 EST sequences against the public database (dbEST) revealed that 139 had
      no significant matches (E-value > 10(-15)) to porcine ESTs already entered in the
      database, suggesting the possibility of their specific expression in porcine
      skeletal muscle. Generation of non-redundant ESTs from this library will allow us
      to construct cDNA microarrays for identification of gene expression changes that
      regulate muscle growth and affect meat quality in swine.

PMID- 12517083
TI  - Mystical mushrooms?

PMID- 12517082
TI  - Commentary: Surrogate decision making: a broader agenda.

PMID- 12517084
TI  - The medical history of chocolate.

PMID- 12517085
TI  - "Remember that I too am mortal": the debut of the ambivalent physician in two
      plays by Shaw and Ibsen.

PMID- 12517086
TI  - Emotional detachment and involvement of physicians in literature.

PMID- 12517087
TI  - The many domains of humanism.

PMID- 12517088
TI  - The many nuances of diversity.

PMID- 12517089
TI  - The many nuances of diversity.

PMID- 12517090
TI  - The many nuances of diversity.

PMID- 12517091
TI  - Referral for abortion.

PMID- 12517092
TI  - More memories of Dr. Barney Brooks.

PMID- 12517093
TI  - Bacteriological and genetic assessment of game meat from Japanese wild boars.
AB  - Bacterial tests were used to assess bacterial contamination of game meat from
      Japanese wild boars. The bacterial contamination of wild boar meat was less than
      that of domestic pork, as determined by aerobic plate counts (APC) and coliform
      counts. None of the meat examined in this study was contaminated by Salmonella or
      E. coli O-157. To detect adulteration by domestic pig meat or European wild boar
      meat, 46 samples of game meat sold as Japanese wild boar were examined
      genetically. A total of 17 samples showed genetic haplotypes of European and
      Asian domestic pigs in the D-loop of mitochondrial DNA (mtDNA), and 16 samples
      showed nuclear glucosephosphate isomerase-processed pseudogene (GPIP) genotypes
      of European domestic pigs. The European GPIP genotypes of these samples were
      confirmed by PCR-RFLP analysis. These results indicate that some game meat sold
      as Japanese wild boar is adulterated by cross-breeding between pigs and wild
      boars or by contamination with meat from domestic pigs or European wild boars.

PMID- 12517094
TI  - Ion chromatography of phytate in roots and tubers.
AB  - The ion chromatographic method for the quantification of phytate (InsP(6)) in
      foods was adapted for the analysis of roots and tubers. To maximize sensitivity,
      ultraviolet (UV) detection following postcolumn derivatization was compared with
      evaporative light-scattering detection (ELSD). Detection limits for phytate were
      0.5 and 1 microg for UV and ELSD, respectively. Unidentified peaks eluting close
      to and after InsP(6) were removed by solid-phase extraction. Phytate was detected
      in 11 of 15 roots or tubers. The highest phytate levels were 0.169 and 0.133% of
      the fresh weight of taro (Colocasia esculenta) and yuca (Manihot esculenta),
      respectively. Potatoes (Solanum tuberosum) contained 0.035-0.073% phytate,
      whereas no phytate at a detection limit of 0.003% of fresh weight was observed in
      sweet potatoes (Ipomoea batatas).

PMID- 12517095
TI  - A method for the analysis of natural and synthetic folate in foods.
AB  - The essentiality of dietary folates for human beings has been known for many
      years. Over the shorter term, biological activities associated with several human
      maladies and the attenuation of biomarkers for several chronic diseases also have
      been assigned to folates. In the United States, these observations have led to
      the addition of folic acid to several foods and food ingredients (food
      fortification) and to dietary recommendations that assign biological activity to
      each of the forms of folate in the food supply. There currently is unavailable a
      robust, instrumental procedure that will distinguish between naturally occurring
      food folates and synthetic folic acid as part of the routine analysis of foods.
      The procedure proposed in this publication is unique in that it uses "off-the
      shelf" supplies and instrumentation, to the extent possible, and was developed
      with "normal" corporate work schedules in mind. This method takes advantage of
      the tri-enzyme food digestion and folate deconjugation steps but was optimized
      with a commercially available rat plasma as the source of conjugase. A high
      capacity styrene-divinylbenzene-based solid-phase extraction column was
      identified, and conditions were developed for quantitative recovery of 5
      methyltetrahydrofolate and folic acid (FA) with it. The various forms of food
      folates are separated on a C-18 high-performance liquid chromatography (HPLC)
      column which is resistant to degradation at low pH. As a result, the mobile phase
      was simplified to a gradient of low-pH phosphate buffer (pH 2.2) and
      acetonitrile. Although FA does not exhibit fluorescence, a UV-induced photolysis
      system was added, which is controlled by the HPLC system, so that an appropriate
      segment of the HPLC column effluent is subjected to photolytic conditions and,
      thereby, FA can be measured as a fluorescent product. The application of the
      system was verified by analyzing several certified reference materials and foods
      and comparing results with certified values and/or total folate values as
      determined by microbiological assay.

PMID- 12517096
TI  - Synthesis and fungistatic activity of new groups of 2,4-dihydroxythiobenzoyl
      derivatives against phytopathogenic fungi.
AB  - Twenty-six compounds, derivatives of amides, hydrazines, hydrazides, hydrazones,
      and semicarbazides, with a 2,4-dihydroxythiobenzoyl moiety, were synthesized from
      sulfinyl-bis(2,4-dihydroxythiobenzoyl). The compositions and chemical structures
      of these compounds were confirmed by IR, (1)H NMR, EI-MS, and elemental analysis.
      Antifungal properties of chemicals under in vitro conditions against five
      phytopathogenic fungi were estimated. In vivo studies against Erisiphe graminis
      were also carried out. The compounds N-substituted with an 2,4
      dihydroxythiobenzamide group proved to be the most active. N-2-(1-Cinnamylbenzene
      ester)-2,4-dihydroxythiobenzamide, under in vitro conditions, showed activity at
      the level of 80-100% development of most pathogens at a concentration of 20
      microg/mL and partially at a concentration of 200 microg/mL. For compounds with 
      HN-NH- or -NH-N= moiety, weak or no fungistatic properties were found at the
      concentrations studied.

PMID- 12517097
TI  - Antifeedant and insecticide properties of a limonoid from Melia azedarach
      (Meliaceae) with potential use for pest management.
AB  - In the course of screening for novel naturally occurring insecticides from
      plants, the activity of the fruit extract of the Argentinian Melia azedarach L.
      (Meliaceae) and its recently described limonoid meliartenin were investigated.
      The antifeedant activity of the fruit extract was tested on a variety of
      herbivore and granivorous insects through choice tests. Sixteen of 17 species
      belonging to three orders consume significantly less food when treated with the
      extract. The bioactivity of the isolated active compound meliartenin and its
      interchangeable isomer 12-hydroxiamoorastatin (1) was further studied. In choice
      tests, compound 1 inhibited feeding of Epilachna paenulata Germ. (Coleoptera,
      Coccinellidae) larvae, with an ED(50) value of 0.80 microg/cm(2), comparable to
      that of azadirachtin (2) and lower than that of toosendanin (3) (0.72 and 3.69
      microg/cm(2), respectively), both compounds used for comparison purposes. In no
      choice tests, E. paenulata larvae reared on food treated with 1 or 2 ate less,
      gained less weight, and suffered greater mortality rates than control larvae. The
      activity of compound 1 was comparable to that of 2, with LD(50) values of 0.76
      and 1.24 microg/cm(2), respectively, at 96 h. Shorter LT(50) values were recorded
      for 1 at 4 and 1 microg/cm(2) in comparison with 2. Thus, M. azedarach fruit
      extract and its active principle have interesting potential for use in pest
      control programs.

PMID- 12517098
TI  - Subcritical water extraction of antioxidant compounds from rosemary plants.
AB  - Subcritical water extraction at several temperatures ranging from 25 to 200
      degrees C has been studied to selectively extract antioxidant compounds from
      rosemary leaves. An exhaustive characterization of the fractions obtained using
      subcritical water at different temperatures has been carried out by LC-MS, and
      the antioxidant activities of the extracts have been measured by a free radical
      method (DPPH). Results indicate high selectivity of the subcritical water toward
      the most active compounds of rosemary such as carnosol, rosmanol, carnosic acid,
      methyl carnosate, and some flavonoids such as cirsimaritin and genkwanin. The
      antioxidant activity of the fractions obtained by extraction at different water
      temperatures was very high, with values around 11.3 microg/mL, comparable to
      those achieved by SFE of rosemary leaves. A study of the effect of the
      temperature on the extraction efficiency of the most typical rosemary antioxidant
      compounds has been performed.

PMID- 12517099
TI  - Purification of fusaproliferin from cultures of Fusarium subglutinans by
      preparative high-performance liquid chromatography.
AB  - Thirty-six Fusarium strains were grown on cracked yellow corn and evaluated for
      optimum fusaproliferin production, with Fusarium subglutinans E-1583 producing
      the highest levels (1600 microg/g). Three solvent systems were tested for
      extracting fusaproliferin from the cultures of F. subglutinans E-1583. Methanol
      gave the highest fusaproliferin recovery, followed by methanol/1% aqueous NaCl
      (55:45, v/v) and acetonitrile/methanol/H(2)O (16:3:1, v/v/v). Hexane partitioning
      was effective in removing many impurities from the crude fusaproliferin extracts
      prior to the liquid chromatography step. Fusaproliferin samples were further
      purified by high-performance liquid chromatography (HPLC) with a C18 preparatory
      column using a mobile phase of acetonitrile/H(2)O (80:20, v/v). The purity of the
      fusaproliferin was verified by analytical HPLC, GC/MS, (1)H NMR spectroscopy, and
      electrospray ionization (ESI) MS. The isolated fusaproliferin was shown to be
      free of impurities and can be used as a standard for routine analysis.
      Fusaproliferin was shown to be temperature-sensitive when samples were stored at
      room temperature (20-24 degrees C) for more than several days. After 30 days at 4
      degrees C, approximately 8% of the fusaproliferin had been transformed to
      deacetyl-fusaproliferin; however, samples stored at -20 degrees C for 1 year
      contained only trace amounts of the deacetylated form.

PMID- 12517100
TI  - Insect antifeedant activity of flavones and chromones against Spodoptera litura.
AB  - The antifeedant polymethylated flavones 5-hydroxy-3,6,7,8,4'-heptamethoxyflavone,
      5-hydroxy-3,6,7,8-tetramethoxyflavone, and 5,6-dihydroxy-3,7-dimethoxyflavone
      have been isolated from the cudweed, Gnaphalium affine D. Don (Compositae). These
      flavonoids and authentic analogues showed insect antifeedant activity against the
      common cutworm (Spodoptera litura F.). In a previous paper, it was suggested that
      there was no substituent on the B-ring of the flavonoid for the beneficial
      antifeedant activity against the common cutworm. These flavonoids having a phenyl
      group as the B-ring and the chromone as elimination of the B-ring from the
      flavonoids were used to test the hypothesis of the previously described B-ring
      effect. The known fact is that Sculletaria baicarensis (Rutaceae) produced the 2
      phenyl flavone. Test compounds and their methylated derivatives were prepared
      from this material for the structure-activity relationship (SAR) study of insect
      antifeedant activity. In spite of the 2-phenyl flavonoids, some tested compounds
      did not show any insect antifeedant activity against the common cutworm, although
      these inactive flavonoids were deficient in the 6-substituent group on the A-ring
      of the flavonoid. This 6-position-substituted derivative almost showed strong
      insect antifeedant activity against common cutworm. Moreover, the tested
      flavonoids having a hydroxyl group as a substituent on any of the positions
      tended to increase the activity. These results suggested the importance of the 6
      position substitution on the flavonoid; however, hydrophilic substituents
      decreased the activity. Baicalein (5,6,7-trihydroxyflavone) derivatives did not
      show any activity despite having the 6-substituent derivative. Although the
      activity of some chromones increased the activity of the flavone, the bulky B
      ring was a disadvantage for the antifeedant activity. It was suggested that the
      charge on C(3) and C(5) of the flavonoid was important for the biological
      activity. Additionally, an adequate hydrogen bonding property, which is different
      from lipophilicity, was an advantage for the activity on the basis of a QSAR
      analysis.

PMID- 12517102
TI  - Determination of the chromium content in commercial breakfast cereals in Spain.
AB  - Chromium (Cr) is an essential element, but the content of this element in many
      foodstuffs, including breakfast cereals, is still unknown. For this reason, the
      Cr content in different types of commercially available breakfast cereals in
      Spain (n = 36) was determined by GFAAS following acid mineralization using HNO(3)
      H(2)SO(4)-HClO(4). On validation, the method yielded a recovery rate of 99 +/-
      1.08%. Results indicated that breakfast cereals are rich in Cr, with contents
      ranging between 0.09 +/- 0.04 and 0.55 +/- 0.08 microg.g(-)(1) and a mean content
      of 0.23 +/- 0.12 microg.g(-)(1). Consumption of breakfast cereals by children and
      adolescents in Spain could supply a Cr intake of 6.9 microg/d, i.e., 3.45-13.8%
      of the ESSADI and 19.72% of the RDI.

PMID- 12517101
TI  - High-pressure effects on Maillard reaction between glucose and lysine.
AB  - Glucose-lysine model systems prepared over a range of pH values (5-10) in
      unbuffered and buffered media were incubated at 60 degrees C either under
      atmospheric pressure or at 400 MPa. The results obtained showed that high
      pressure affected in different ways the different stages of the Maillard reaction
      and that such effects were strongly influenced by pressure-induced changes in the
      pH of the systems. In unbuffered media, at an initial pH < or =8.0, the formation
      of Amadori rearrangement products (ARP) was not considerably affected by
      pressure, whereas the intermediate and advanced stages of the Maillard reaction
      were suppressed, suggesting a retardation of the degradation of the ARP. In
      buffered media, at pH values < or =8.0, pressure slowed the Maillard reaction
      from the initial stages. These effects are attributed to the pH drop caused by
      the pressure-induced dissociation of the acid groups. In unbuffered and buffered
      media at initial pH = 10.2, high pressure accelerated the formation and
      subsequent degradation of ARP, leading to increased levels of intermediate and
      advanced reaction products.

PMID- 12517103
TI  - Compositional changes of Australia-grown Western Schley pecans [Carya
      illinoinensis (Wangenh.) K. Koch] during maturation.
AB  - Changes in composition during the maturation of Western Schley pecans [Carya
      illinoinensis(Wangenh.) K. Koch] grown in Australia were investigated. Pecans of
      different maturity levels were collected at monthly intervals between March and
      June in 1999 and 2000 and analyzed for the concentrations of moisture, total
      lipid, sucrose, raffinose, protein, and the minerals aluminum, boron, calcium,
      copper, iron, potassium, magnesium, manganese, sodium, phosphorus, sulfur, and
      zinc. Moisture, total lipid, and calcium contents changed significantly (p <
      0.05) with harvest time and maturity, whereas the other components did not.
      Western Schley pecans grown in Australia should be harvested after the shuck has
      opened and it is either green or brown in color to maximize total lipid content
      and quality. This occurred after May 11 in 1999 and after May 17 in 2000.

PMID- 12517104
TI  - Controlled-release NPK fertilizer encapsulated by polymeric membranes.
AB  - The commercial granular fertilizer NPK6-20-30 was coated using polysulfone (PSF),
      polyacrylonitrile (PAN), and cellulose acetate (CA). The coatings were formed
      from the polymer solutions by the phase inversion technique. Measurements of the
      thickness and porosity of the prepared coatings and a microphotographic
      observation of the coatings were performed. The physical properties of the
      coatings influence the release rate of macronutrients which are present in the
      core of the coated fertilizer. In the case of PAN coating with 60.45% porosity,
      prepared from a 16% polymer solution, 100% of NH(4)(+) and P(2)O(5) was released
      after 4 h of test and 99.7% of K(+) after 5 h of test, whereas in the case of
      coating with 48.8% porosity, 31.8% of NH(4)(+), 16.7% of P(2)O(5), and 11.6% of
      K(+) was released after 5 h. In all experiments, different selectivities of the
      coatings in terms of the release of components were observed. The release of
      potassium through the coatings made of PSF and PAN was the slowest. The same
      tendency was observed for the release of nitrogen through a coating of CA. The
      release of fertilizer active components was the slowest in the case of PSF. The
      lowest porosity coating was prepared from the 18% PSF solution.

PMID- 12517105
TI  - Characterization of Citrus unshiu (C. unshiu Marcov. forma Miyagawa-wase) blossom
      aroma by solid-phase microextraction in conjunction with an electronic nose.
AB  - The volatile composition of the headspace from Citrus unshiu Marcov. forma
      Miyagawa-wase blossom was investigated. The volatile constituents were absorbed
      by a solid-phase microextraction (SPME) fiber and directly transferred to a GC
      MS. Volatile compositional changes of C. unshiu blossom prepared via different
      drying methods (shade, microwave, and freeze-drying methods) were also
      determined. A total of 96 volatile constituents were confirmed in the headspace
      from these samples. Monoterpene hydrocarbons were prominent in the headspace
      volatiles of C. unshiu blossom: fresh, 84.1%; shade-dried, 60.0%; microwave
      dried, 88.4%; and freeze-dried, 29.9%. p-Cymene (23.3%) was the most abundant
      component in the headspace of fresh C. unshiu blossom; gamma-terpinene was the
      most abundant in shade- and microwave-dried samples (26.8 and 31.2%,
      respectively) and beta-caryophyllene (10.5%) in freeze-dried sample. By using an
      electronic nose consisting of six metal oxide sensors, principal component
      analysis of the volatile compounds showed a clear aroma discrimination of the
      fresh and all dried blossom samples.

PMID- 12517106
TI  - Chemical and sensorial aroma characterization of freshly distilled Calvados. 1.
      Evaluation of quality and defects on the basis of key odorants by olfactometry
      and sensory analysis.
AB  - Eight freshly distilled samples of Calvados, a fermented and distilled apple
      juice, were analyzed by sensory evaluation and direct injection GC to determine
      the composition of higher alcohols, esters, and aldehydes. The composition
      determined by direct injection was tentatively related to sensory descriptors.
      Esters have a probable maximum level around 500 g/hl of pure alcohol (PA). This
      level also corresponds to the threshold of the main ester constituent, ethyl
      acetate. A high ratio of esters to ethyl acetate seems to be of prime importance
      for good quality. Total aldehydes, with a maximum level between 8 and 11 g/hl of
      PA and mainly comprising acetal (maximum between 5 and 9 g/hl of PA), were
      related to a "green" descriptor. Higher alcohols do not have a direct impact on
      quality, but other volatile compounds with a positive impact on flavor should
      probably be present at a high level. As overall quality was not well related to
      sensory quality, it was necessary to perform more a precise analysis to determine
      the key odorants. The Calvados samples were thus extracted using pentane. Gas
      chromatography, employing both a flame ionization detector and an olfactometry
      port, was used to analyze the obtained extracts. Seventy-one odors were detected
      and distributed according to Calvados quality determined by sensory evaluation.
      Nineteen odors common to all Calvados samples constituted the "skeleton" of the
      aroma. Twenty-eight odors were specific to a quality class: 6 for good quality, 4
      for neutral, and 18 for defective. Twenty-four other odors had either too low an
      odor impact or no evident specificity.

PMID- 12517107
TI  - Chemical and sensorial aroma characterization of freshly distilled Calvados. 2.
      Identification of volatile compounds and key odorants.
AB  - Eight samples of freshly distilled Calvados were extracted using pentane. Gas
      chromatography with either a mass spectrometer or flame ionization detector was
      used to determine the volatile compounds composition of the extracts. More than
      120 molecules were identified in Calvados and then correlated with results
      obtained by olfactometric analysis in our earlier work [Guichard, H.; Lemesle,
      S.; Ledauphin, J.; Barillier, D.; Picoche, B. Chemical and Sensorial Aroma
      Characterization of Freshly Distilled Calvados. 1. Evaluation of Quality and
      Defects on the Basis of Key Odorants by Olfactometry and Sensory Analysis. J.
      Agric. Food Chem. 2002, 50, 424-432 (preceding paper in this issue)]. Of these,
      16 of the 19 molecules that constitute the "aroma skeleton" were identified,
      including 5 esters, 2 ketones, 5 phenolic derivatives, 2 alcohols, and 2
      carboxylic acids. Numerous compounds were also associated with odors found in
      part 1. These molecules can be considered as being responsible for the good
      quality of Calvados or, in contrast, for defects. Relative levels of some major
      olfactive compounds were also estimated and tentatively compared with
      olfactometric indices found in part 1. A good correlation was found in many
      cases. Two important markers of defects in Calvados were also identified. 3
      Methylbut-2-en-1-ol leads to an "herbaceous" defect, and 1,1,3-triethoxypropane
      seems to give an "acrolein" defect in the product. "Floral" notes of the aroma of
      freshly distilled Calvados seem to be due to the presence of phenolic derivatives
      such as 2-phenylethanol and 2-phenylethyl acetate. Low-molecular-weight esters
      such as ethyl 2-methylpropanoate, ethyl 2-methylbutanoate, and 3-methylbutyl
      acetate give, in general, the "fruity" notes. However, the overall aroma of
      Calvados seems likely to be a subtle balance of various functionalized compounds.

PMID- 12517108
TI  - A new approach to examine the relationships between sensory and gas
      chromatography-olfactometry data using Generalized Procrustes analysis applied to
      six French Chardonnay wines.
AB  - Six French Chardonnay wines were submitted to both sensory and combined
      headspace/gas chromatography-olfactometry analyses. The detection frequencies
      allowed five hierarchical levels to be distinguished: P25, the odorant areas
      (OAs) having a detection frequency > or =25% (the complete olfactogram without
      the odor noise); P40, > or =40%; P55, > or =55%; P70, > or =70%; and P85, > or
      =85%. Moreover, the detection frequencies were analyzed to distinguish 21
      discriminative OAs. Wines tested by sensory analysis and the headspace samples
      analyzed by gas chromatography-olfactometry (GC-O) were described by a
      heterogeneous vocabulary distributed into nine overall classes of descriptors.
      The new statistical treatment to examine hierarchical or discriminative OA
      categories with respect to sensory data used Generalized Procrustes analysis
      (GPA) from coordinate tables provided by correspondence analysis (CA). The
      successive data sets supplied by CA were subjected to GPA to yield consensus
      method maps. The more selective levels of detection frequency (P70 and P85) were
      responsible for incomplete or distorted information with respect to sensory data.
      The most appropriate segmentation of the OA distribution (olfactogram) to
      represent the sensory profile of the six samples would correspond to the
      intermediate pattern (P40 and P55). The other interest was to study the reasons
      of distortion due to the dynamic headspace extraction. The highest proportions of
      the variance were at all times related to the same classes: spicy, herbaceous,
      and, to a lesser degree, microbiological. This would indicate that the dynamic
      headspace analysis induces a distortion with respect to sensory data, which
      systematically affected the perception of both spicy and herbaceous characters of
      wines.

PMID- 12517109
TI  - The effects of temperature and pressure on the characteristics of the extracts
      from high-pressure CO(2) extraction of Majorana hortensis Moench.
AB  - The aim of this work is to assess the influence of temperature and pressure
      (solvent density) on the characteristics of the essential oil obtained from high
      pressure carbon dioxide extraction of marjoram (commercial marjoram samples
      available in the free market and Majorana hortensis Moench, cultivated in South
      Brazil under rigorous agronomic conditions). The extracts were analyzed in terms
      of the liquid yield (extract/raw material, wt/wt) and distribution of volatile
      chemical components. The experiments were performed in a laboratory-scale unit
      using the dynamic method in the temperature range of 293.15-313.15 K, from 100 to
      200 bar in pressure. Chemical analyses were carried out in a GC/MSD. Results show
      that an increase in temperature leads to a rise in the extract liquid yield
      despite large changes in solvent density. Chromatographic analyses permitted the
      identification of cis-sabinene hydrate, terpineol-4, alpha-terpineol, and cis
      sabinene hydrate acetate as the main volatile compounds present in both
      commercial and cultivated samples.

PMID- 12517110
TI  - Identification and quantitation of the rice aroma compound, 2-acetyl-1-pyrroline,
      in bread flowers (Vallaris glabra Ktze).
AB  - The aroma impact compound, 2-acetyl-1-pyrroline (2AP), has been identified for
      the first time in headspace of fresh bread flowers (Vallaris glabra Ktze) in
      which volatile components were extracted by solid-phase microextraction (SPME) at
      room temperature prior to analysis by gas chromatography-mass spectrometry. A
      total of 50 volatiles were detected. Among these, 23 volatiles were identified,
      predominantly in a group of terpenes. More volatiles were found in the extract of
      fresh bread flowers obtained by continuous steam distillation and solvent
      extraction (SDS). Of the 40 volatiles identified, the additional components were
      mainly straight-chain saturated hydrocarbons. 2AP was found in the extracts
      obtained by both SPME (0.37%) and SDS (2.71% relative proportion). Quantitative
      analyses of 2AP in bread flowers and other plant materials were performed by
      solvent extraction employing acidic solutions and capillary GC with flame
      ionization detection. The highest concentration of 2AP was found in dried flowers
      of V. glabra at 26.1 mg/kg. By comparison with other plant sources, fresh leaves
      of Pandanus amaryllifolius Roxb contain 2AP at 10.3 mg/kg and Thai fragrant rice,
      Khao Dawk Mali 105, at 3.0 mg/kg.

PMID- 12517111
TI  - Biogenetic studies in Syringa vulgaris L.: synthesis and bioconversion of
      deuterium-labeled precursors into lilac aldehydes and lilac alcohols.
AB  - Syringa vulgaris L. inflorescences were fed with aqueous solutions of
      regioselectively deuterated compounds assumed to be precursors of lilac aldehyde
      and lilac alcohol, respectively. Volatiles were extracted by stir bar sorptive
      extraction (SBSE) and analyzed using enantioselective multidimensional gas
      chromatography/mass spectrometry (enantio-MDGC/MS); deuterium-labeled lilac
      aldehydes and lilac alcohols were separated from unlabeled stereoisomers on a
      fused silica capillary column, coated with heptakis(2,3-di-O-methyl-6-O-tert
      butyldimethylsilyl)-beta-cyclodextrin (DIME-beta-CD) (30%) in SE 52 (70%), as the
      chiral stationary phase. Feeding experiments with [5,5-(2)H(2)]mevalonic acid
      lactone 22 and [5,5-(2)H(2)]deoxy-d-xylose 23 indicate that the novel mevalonate
      independent 1-deoxy-d-xylose 5-phosphate/2C-methyl-d-erythritol 4-phosphate
      pathway is the dominant metabolic route for biosynthesis in lilac flowers.
      Additionally, bioconversion of deuterium-labeled d(5)-(R/S)-linalool 3, d(6)-(R)
      linalool 21, d(5)-(R/S)-8-hydroxylinalool 6, d(5)-(R/S)-8-oxolinalool 7, d(5)
      lilac aldehydes 8-11 and d(5)-lilac alcohols 12-15 into lilac during in vivo
      feeding experiments was investigated and the metabolic pathway is discussed.
      Incubation of petals with an aqueous solution of deuterated d(5)-(R/S)-linalool 3
      indicates an autonomic terpene biosynthesis of lilac flavor compounds in the
      flower petals of lilac.

PMID- 12517112
TI  - Fluorescence of muscle and connective tissue from cod and salmon.
AB  - Autofluorescence of salmon and cod muscle was measured and compared with
      autofluorescence of collagen type I and type V. Similarities between fluorescence
      of fish muscle and collagen were found in that the same peaks were obtained
      around 390, 430, and 480 nm. These similarities are supported by principal
      component analyses. Texture and gaping score were predicted from the fluorescence
      spectra by partial least-squares regression. However, the predictions did not
      perform well. Relating fluorescence to the gaping score gave a prediction error
      of 0.91 and a correlation of 0.43 when measuring gaping on a scale from 0 to 5.
      There was no relation between texture and fluorescence spectra. Fluorescence of
      fish muscle could be related to the storage time. However, this relation seemed
      not to be induced by changes in collagen.

PMID- 12517113
TI  - Solubilization of acyl heterogeneous triacylglycerol in phosphatidylcholine
      vesicles.
AB  - The amount of acyl heterogeneous triacylglycerol (TG(HET)) solubilized by
      phosphatidylcholine (PC) vesicles, prepared by co-sonication of egg PC and small
      amounts (<6% w/w) of TG(HET), was determined using (13)C nuclear magnetic
      resonance (NMR). The acyl chains of TG(HET) were predominantly 16 or 18 carbons
      in length, 50% saturated, and approximately 21.7% (13)C isotopically enriched at
      the carbonyl carbon. The (13)C NMR spectra revealed two carbonyl resonances at
      chemical shift values between PC carbonyls and oil-phase TG carbonyls, confirming
      the presence of TG(HET) solubilized in PC vesicles. Oil-phase TG carbonyl peaks
      were present only in spectra of vesicles containing >3 wt % TG(HET). Integration
      of TG(HET) carbonyl resonances determined that PC vesicles solubilized 3.8 wt %
      of TG(HET), compared to 2.8 wt % of acyl homogeneous triolein. The difference
      between the maximum solubility of TG(HET) and that of homogeneous TG (TG(HOM))
      with similar acyl chain lengths provides evidence that specific acyl composition,
      in addition to the acyl chain length of triacylglycerols, affects the solubility
      of TG in PC vesicles and TG-rich lipoprotein surfaces. Thus, TG(HET) may innately
      be a better model substrate than TG(HOM) for determination of substrate
      availability of TG at lipoprotein surfaces.

PMID- 12517114
TI  - New Saccharomyces cerevisiae baker's yeast displaying enhanced resistance to
      freezing.
AB  - Three procedures were used to obtain new Saccharomyces cerevisiae baker's yeasts
      with increased storage stability at -20, 4, 22, and 30 degrees C. The first used
      mitochondria from highly ethanol-tolerant wine yeast, which were transferred to
      baker's strains. Viability of the heteroplasmons was improved shortly after
      freezing. However, after prolonged storage, viability dramatically decreased and
      was accompanied by an increase in the frequency of respiratory-deficient (petite)
      mutant formation. This indicated that mitochondria were not stable and were
      incompatible with the nucleus. The strains tested regained their original
      resistance to freezing after recovering their own mitochondria. The second
      procedure used hybrid formation after protoplast fusion and isolation on
      selective media of fusants from baker's yeast meiotic products resistant to
      parafluorphenylalanine and cycloheximide, respectively. No hybrids were obtained
      when using the parentals, probably due to the high ploidy of the baker's strains.
      Hybrids obtained from nonisogenic strains manifested in all cases a resistance to
      freezing intermediate between those of their parental strains. Hybrids from
      crosses between meiotic products of the same strain were always more sensitive
      than their parentals. The third method was used to develop baker's yeast mutants
      resistant to 2-deoxy-d-glucose (DOG) and deregulated for maltose and sucrose
      metabolism. Mutant DOG21 displayed a slight increase in trehalose content and
      viability both in frozen doughs and during storage at 4 and 22 degrees C. This
      mutant also displayed a capacity to ferment, under laboratory conditions, both
      lean and sweet fresh and frozen doughs. For industrial uses, fermented lean and
      sweet bakery products, both from fresh and frozen doughs obtained with mutant
      DOG21, were of better quality with regard to volume, texture, and organoleptic
      properties than those produced by the wild type.

PMID- 12517115
TI  - Effects of xylanase treatments on gelling and water-uptaking properties of
      psyllium.
AB  - The effects of a commercial food-grade xylanase on the physicochemical properties
      of psyllium were evaluated. The enzymatic reactions were conducted in solid state
      at ambient temperature. The enzyme-treated psyllium preparations were analyzed
      and compared with the starting psyllium for their water-uptake properties,
      gelling capacities, soluble and insoluble fiber contents, and surface structures.
      The solid-state xylanase treatment significantly reduced both water-uptake and
      gelling capacities of psyllium (p < 0.01), with a slight decrease of soluble
      fiber content, whereas no effect on insoluble fiber content was observed. The
      xylanase treatment also resulted in a smoother surface structure of psyllium
      particles. In addition, no special equipment and operation were required to
      conduct the enzymatic reaction, which generated no waste. These data indicated a
      potential to improve the physicochemical properties of psyllium by use of the
      solid-state xylanase reactions to promote the utilization of psyllium fiber in
      functional foods for promoting human health.

PMID- 12517116
TI  - Antioxidant constituents of almond [Prunus dulcis (Mill.) D.A. Webb] hulls.
AB  - Almond hulls (Nonpareil variety) were extracted with methanol and analyzed by
      reversed phase HPLC with diode array detection. The extract contained 5-O
      caffeoylquinic acid (chlorogenic acid), 4-O-caffeoylquinic acid
      (cryptochlorogenic acid), and 3-O-caffeoylquinic acid (neochlorogenic acid) in
      the ratio 79.5:14.8:5.7. The chlorogenic acid concentration of almond hulls was
      42.52 +/- 4.50 mg/100 g of fresh weight (n = 4; moisture content = 11.39%).
      Extracts were tested for their ability to inhibit the oxidation of methyl
      linoleate at 40 degrees C. At an equivalent concentration (10 microg/1 g of
      methyl linoleate) almond hull extracts had higher antioxidant activity than alpha
      tocopherol. At higher concentrations (50 microg/1 g of methyl linoleate) almond
      hull extracts showed increased antioxidant activity that was similar to
      chlorogenic acid and morin [2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1
      benzopyran-4-one] standards (at the same concentrations). These data indicate
      that almond hulls are a potential source of these dietary antioxidants. The
      sterols (3beta,22E)-stigmasta-5,22-dien-3-ol (stigmasterol) and (3beta)-stigmast
      5-en-3-ol (beta-sitosterol) (18.9 mg and 16.0 mg/100 g of almond hull,
      respectively) were identified by GC-MS of the silylated almond hull extract.

PMID- 12517117
TI  - Oxygen radical absorbing capacity of phenolics in blueberries, cranberries,
      chokeberries, and lingonberries.
AB  - The antioxidant activity of phenolics in fruits of blueberry (Vaccinium
      corymbosum cv. Sierra), cranberry (Vaccinium macrocarpon cv. Ben Lear), wild
      chokeberry (Aronia melanocarpa), and lingonberry (Vaccinium vitis-idaea cv.
      Amberland) was determined in this study. The phenolic constituents and contents
      among the different berries varied considerably. Anthocyanins were found to be
      the main components in all these berries. Chlorogenic acid in blueberry,
      quercetin glycosides in cranberry and lingonberry, and caffeic acid and its
      derivative in chokeberry were also present in relatively high concentrations.
      Chlorogenic acid, peonidin 3-galactoside, cyanidin 3-galactoside, and cyanidin 3
      galactoside were the most important antioxidants in blueberry, cranberry, wild
      chokeberry, and lingonberry, respectively. The contribution of individual
      phenolics to the total antioxidant capacity was generally dependent on their
      structure and content in the berries. Phenolics such as quercetin and cyanidin,
      with 3',4'-dihydroxy substituents in the B ring and conjugation between the A and
      B rings, had highly effective radical scavenging structures in blueberries,
      cranberries, chokeberries, and lingonberries. Phenolic acids such as caffeic acid
      also showed high antioxidant activity, probably due to its dihydroxylation in the
      3,4 positions as hydrogen donors.

PMID- 12517118
TI  - Epimerization of tea catechins and O-methylated derivatives of (-)
      epigallocatechin-3-O-gallate: relationship between epimerization and chemical
      structure.
AB  - Epimerization at C-2 of O-methylated catechin derivatives and four major tea
      catechins were investigated. The epimeric isomers of (-)-epicatechin (I), (-)
      epicatechin-3-O-gallate (II), (-)-epigallocatechin (III), (-)-epigallocatechin-3
      O-gallate (IV), and (-)-epigallocatechin-3-O-(3-O-methyl)gallate (V) in green tea
      extracts increased time-dependently at 90 degrees C. The epimerization rates of
      authentic tea catechins in distilled water are much lower than those in tea
      infusion or in pH 6.0 buffer solution. The addition of tea infusion to the
      authentic catechin solution accelerated the epimerization, and the addition of
      ethylenediaminetetraacetic acid, disodium salt (Na(2)EDTA) decreased the
      epimerization in the pH 6.0 buffer solution. Therefore, the metal ions in tea
      infusion may affect the rate of epimerization. The proportions of the epimers to
      authentic tea catechins [III, IV, V, and (-)-epigallocatechin-3-O-(4-O
      methyl)gallate (VI)] in pH 6.0 buffer solution after heating at 90 degrees C for
      30 min were 42.4%, 37.0%, 41.7%, and 30.4%, respectively. These values were
      higher than those of I and II (23.5% and 23.6%, respectively). The O-methylated
      derivatives at the 4'-position on the B ring of IV and VI were hardly epimerized.
      These results suggest that the hydroxyl moiety on the B ring of catechins plays
      an important role in the epimerization in the order 3',4',5'-triol type > 3',4'
      diol type >> 3',5'-diol type.

PMID- 12517119
TI  - Effect of different soaking solutions on nutritive utilization of minerals
      (calcium, phosphorus, and magnesium) from cooked beans (Phaseolus vulgaris L.) in
      growing rats.
AB  - The effects of the commonly used processing techniques of soaking (at different
      pH values) and cooking on the digestive and nutritive utilization of calcium,
      phosphorus, and magnesium from common beans (Phaseolus vulgaris L.) were studied.
      Before the cooking step, the beans were soaked in solutions of acid (2.6 and 5.3)
      or basic (8.4) pH. Chemical and biological methods were used to determine
      nutritional parameters in growing rats, and the fiber content of the beans was
      established. As the pH of the soaking solution increased, so did mineral
      absorption and the apparent digestibility coefficient, which reached suitable
      values for growing rats, due to the reduced losses of soluble minerals and the
      increased food intake. Metabolic utilization also improved with increased pH of
      the soaking solution, although the values were, in general, low as a result of
      urinary losses under the experimental conditions. For the experimental period of
      10 days, the femur and the muscle seem to be good metabolic indicators for
      calcium, but not for phosphorus or magnesium. The increased amount of cellulose
      in the soaked seed did not have a negative effect on the digestive utilization of
      minerals.

PMID- 12517120
TI  - An improved method for the purification of the trichothecene deoxynivalenol
      (vomitoxin) from Fusarium graminearum culture.
AB  - It was hypothesized that a simplified and efficient strategy could be developed
      for large-scale production and purification of the mycotoxin deoxynivalenol from
      Fusarium graminearum rice cultures for toxicological studies. F. graminearum
      R6576 was cultured on rice and extracted with methanol, and the extract was
      concentrated and subjected to silica gel low-pressure liquid chromatography
      (LPLC) under a hexane-acetone gradient system. Deoxynivalenol isolation was
      monitored by thin-layer chromatography, and fractions containing deoxynivalenol
      were pooled, concentrated, and applied to a second LPLC column under the same
      conditions. An enriched deoxynivalenol fraction was obtained, which yielded a
      crystalline material. Repeated crystallization yielded spectroscopically pure
      deoxynivalenol. The identity of this compound was confirmed by HPLC comparison to
      an authentic deoxynivalenol standard, FABMS analysis, and comparison of the (1)H
      and (13)C NMR spectra with published data. This simplified purification scheme
      eliminated many laborious steps and equipment previously required to obtain gram
      quantities of crystalline deoxynivalenol for biological testing in animal models.

PMID- 12517121
TI  - p-Hydroxybenzoic acid alkyl esters in Andrographis paniculata herbs, commercial
      extracts, and formulated products.
AB  - Analysis of two commercial extracts of Andrographis paniculata using high
      performance liquid chromatography (HPLC) with photodiode array absorbance
      detection showed the presence of several unexpected compounds, which were
      isolated and identified as methyl, ethyl, and propyl esters of p-hydroxybenzoic
      acid by using high-resolution mass spectrometry and nuclear magnetic resonance.
      Quantitative analysis using HPLC revealed the presence of 0.22% p-hydroxybenzoic
      acid methyl ester (methlyparaben) in one commercial extract, and both 0.11% p
      hydroxybenzoic acid ethyl ester (ethylparaben) and 0.20% p-hydroxybenzoic acid
      propyl ester (propylparaben) in a second commercial extract of A. paniculata.
      Analyses of additional commercial products of A. paniculata in tablet form
      purchased from Chicago pharmacies also showed the presence of methyl- and
      ethylparabens. To determine whether these compounds were natural chemical
      constituents of the plant, pharmacopoeial reference A. paniculata plant powder as
      well as samples of authenticated A. paniculata plant materials collected from
      Indonesia, Hong Kong, and mainland China were obtained and analyzed by HPLC
      tandem mass spectrometry (LC-MS-MS). LC-MS-MS analyses confirmed the presence of
      trace concentrations (<0.0008% w/w) of p-hydroxybenzoic acid methyl ester but no
      p-hydroxybenzoic acid ethyl or propyl esters in these plant samples. The limits
      of detection of the LC-MS-MS assay for these compounds were 5 pg on-column and 5
      ppb in the plant material. The levels of these p-hydroxybenzoic acid esters
      measured in the commercial products of A. paniculata suggest that they were
      introduced inadvertently during processing or as artificial additives.

PMID- 12517123
TI  - Aerobic oxidation of methyl p-tolyl sulfide catalyzed by a remarkably labile
      heteroscorpionate RuII-aqua complex, fac-[RuII(H2O)(dpp)(tppm)]2+.
AB  - fac-[RuII(Cl)(dpp)(L3)]+ (L3 = tris(pyrid-2-yl)methoxymethane (tpmm) = [1A]+ and
      tris(pyrid-2-yl)pentoxymethane (tppm) = [1B]+ and dpp = di(pyrazol-1-yl)propane)
      rapidly undergo ligand substitution with water to form fac-[RuII(H2O)(dpp)(L3)]2+
      (L3 = tpmm = [2A]2+ and tppm = [2B]2+). In the structure of [2A]2+, the distorted
      octahedral arrangement of ligands around Ru is evident by a long Ru(1)-O(40) of
      2.172(3) A and a large angle O(40)-Ru(1)-N(51) of 96.95(14) degrees . The
      remarkably short distance between O(40) of H2O and H(45a) of dpp confirms the
      heteroscorpionate ligand effect of dpp on H2O. [2B]2+ aerobically catalyzes
      methyl p-tolyl sulfide to methyl p-tolyl sulfoxide in 1,2-dichlorobenzene at 25.0
      +/- 0.1 degrees C under 11.4 psi of O2. Experimental facts in support of this
      aerobic sulfide oxidation are the absence of H2O2 and the oxidative reactivity of
      the putative Ru(IV)-oxo intermediate toward methyl p-tolyl sulfide, 2-propanol,
      and allyl alcohol. This study provides the first documented example of aerobic
      sulfide oxidation catalyzed by the remarkably labile heteroscorpionate Ru(II)
      aqua complex without the formation of a highly reactive peroxide as an
      intermediate.

PMID- 12517124
TI  - Migration of methyl groups between aliphatic amines in water.
AB  - Glycine undergoes spontaneous decarboxylation in dilute aqueous solution at
      elevated temperatures to form methylamine. During that process, we noticed the
      appearance of dimethylamine and trimethylamine in smaller amounts that increased
      gradually with time. These observations suggested the existence of
      disproportionation reactions of methylamines in water, for which there appears to
      be no direct precedent in the literature. Every member of the methylamine series
      is found to yield other members of the methylamine series. When the total
      concentration of amine was held constant and the rate of reaction was examined as
      a function of changing pH using the amine itself as the buffer, the initial rate
      of appearance of the products was found to reach a maximum when the conjugate
      acid and the conjugate base were present at equivalent concentrations. Near this
      equivalence point, the rate of reaction varied with pH as expected for a second
      order reaction between the protonated and the unprotonated species. Under similar
      conditions, methyl groups were also found to migrate between the nitrogen atoms
      of N,N-dimethyl-1,3-propanediamine in a first-order process. With dimethylamine
      as a common acceptor, trimethylsulfonium ion was found to be approximately 104
      fold more reactive than the tetramethylammonium ion at ambient temperature.

PMID- 12517125
TI  - An unusually slow self-assembly of inorganic ions in dilute aqueous solution.
AB  - A combination of static and dynamic laser light-scattering techniques was used to
      monitor an unusual slow self-assembly of giant polyoxomolybdate-based molecules
      into vesicle structures in dilute aqueous solution. Contrary to the behavior of
      common inorganic ions, these giant molecules need months to reach an equilibrium
      state. The process is an endothermic process and roughly follows the rule of a
      first-order reaction. The possible reasons for such a slow solution process are
      also discussed.

PMID- 12517126
TI  - Polyaniline nanofibers: facile synthesis and chemical sensors.
AB  - Polyaniline nanofibers with uniform diameters between 30 and 50 nm can be made in
      bulk quantities through a facile aqueous/organic interfacial polymerization
      method at ambient conditions. The nanofibers have lengths varying from 500 nm to
      several micrometers and form interconnected networks. Thin films made of the
      nanofibers have superior performance in both sensitivity and time response to
      vapors of acid (HCl) and base (NH3).

PMID- 12517127
TI  - Preparation of novel silica-cadmium sulfide composite nanoparticles having
      adjustable void space by size-selective photoetching.
AB  - The size-selective photoetching technique was used to control the size of a CdS
      nanoparticle inside a silica shell. With monochromatic light irradiation, the
      diffuse reflectance spectra of silica-coated CdS nanoparticles were blue-shifted,
      and the size of the resulting CdS nanoparticles incorporated in the silica shells
      was adjustable by varying the wavelength of irradiated light. TEM observation
      revealed that the original CdS nanoparticle seemed to be in close contact with
      the amorphous silica shell to leave almost no clearance, while the monochromatic
      light irradiation caused the decrease in the size of CdS particles, resulting in
      the formation of a void space between the photoetched CdS core particle and the
      silica shell. The average void spaces available in the shells were calculated to
      be ca. 1.4 and 2.4 nm with the irradiation at 514 and 458 nm, respectively. These
      results indicated that the size-selective photoetching technique enables the
      regulation of void space formed in the core-shell structure by choosing the
      wavelength of irradiation light.

PMID- 12517128
TI  - Reduction and methyl transfer kinetics of the alpha subunit from acetyl coenzyme
      a synthase.
AB  - Stopped-flow was used to evaluate the methylation and reduction kinetics of the
      isolated alpha subunit of acetyl-Coenzyme A synthase from Moorella thermoacetica.
      This catalytically active subunit contains a novel Ni-X-Fe4S4 cluster and a
      putative unidentified n = 2 redox site called D. The D-site must be reduced for a
      methyl group to transfer from a corrinoid-iron-sulfur protein, a key step in the
      catalytic synthesis of acetyl-CoA. The Fe4S4 component of this cluster is also
      redox active, raising the possibility that it is the D-site or a portion thereof.
      Results presented demonstrate that the D-site reduces far faster than the Fe4S4
      component, effectively eliminating this possibility. Rather, this component may
      alter catalytically important properties of the Ni center. The D-site is reduced
      through a pathway that probably does not involve the Fe4S4 component of this
      active-site cluster.

PMID- 12517129
TI  - Semiconductor nanocrystals with multifunctional polymer ligands.
AB  - In this letter, we describe the preparation of a versatile polymer ligand, which
      can be attached to CdSe/ZnS semiconductor nanocrystals via a phase transfer
      reaction. The ligand is based on a chain of reactive esters, which can, in
      principle, be substituted by any compound containing amino-functionalities. The
      polymer/nanocrystal complexes are characterized in terms of structure and
      photostability.

PMID- 12517130
TI  - A low-spin d5 iron imide: nitrene capture by low-coordinate iron(I) provides the
      4-coordinate Fe(III) complex [PhB(CH2PPh2)3]Fe=N-p-tolyl.
AB  - Entry into "[PhBP3]Fe" chemistry affords a rare, pseudotetrahedral iron(I)
      complex, [PhBP3]Fe(PPh3), with an S = 3/2 ground state. This precursor undergoes
      rapid oxidation by aryl azide to produce the d5 imide [PhBP3]FeNAr (Ar = p
      tolyl). The Fe(III) imide is significant in that it is low-spin and represents
      the first mononuclear imide of iron. Doublet [PhBP3]FeNAr reacts rapidly and
      quantitatively with CO at room temperature to release isocyanate and
      [PhBP3]Fe(CO)2. The [PhBP3]Fe(CO)2 byproduct is also a precursor to [PhBP3]FeNAr
      upon addition of aryl azide.

PMID- 12517131
TI  - Label-free DNA hybridization probe based on a conducting polymer.
AB  - A new approach to the realization of the electrochemical DNA hybridization probe
      is described. It is based on the exchange of chloride ion between the polypyrrole
      layer and the buffer. The shape of the cyclic voltammogram is modulated by the
      negative charge density at this interface, resulting from the immobilized target
      DNA. The negative charge density increases when the complementary DNA hybridizes
      with the probe DNA. The hybridization event can be clearly seen in the cyclic
      voltammogram before and after the addition of the probe DNA. The immobilization
      is accomplished via the Mg2+ bridging complex between phosphonic acid groups of
      the poly[2,5-dithienyl-(N-3-phosphorylpropyl)pyrrole] grafted at the polypyrrole
      surface and the phosphate groups of the target DNA.

PMID- 12517132
TI  - Charge ordering in lithium vanadium phosphates: electrode materials for lithium
      ion batteries.
AB  - The delithiation process in monoclinic Li3V2(PO4)3 has been determined by powder
      neutron diffraction coupled with 7Li solid-state NMR techniques. Charge ordering
      of vanadium (V3+/V4+) was observed in Li2V2(PO4)3 as shown by the gray and blue V
      O octahedra, respectively, indicating that the electrons are pinned in this phase
      and hence transport is limited.

PMID- 12517134
TI  - Reversible binding of the HPLC6 isoform of type I antifreeze proteins to ice
      surfaces and the antifreeze mechanism studied by multiple quantum filtering-spin
      exchange NMR experiment.
AB  - Antifreeze proteins (AFPs) protect organisms from freezing damage by inhibiting
      the growth of seed-ice crystals. It has long been hypothesized that irreversible
      binding of AFPs to ice surfaces is responsible for inhibiting the growth of seed
      ice crystals as such a mechanism supports the popularly accepted Kelvin effect
      for the explanation of local freezing-point depression. However, whether the
      binding is reversible or irreversible is still under debate due to the lack of
      direct experimental evidence. Here, we report the first direct experimental
      result, by using the newly developed multiple quantum (MQ) filtering-spin
      exchange NMR experiment, that shows that the binding of HPLC6 peptides to ice
      surfaces is reversible. It was found that the reversible process can be explained
      by the model of monolayer adsorption. These results suggest that the Kelvin
      effect is not suitable for explaining the antifreeze mechanism, and direct
      interactions between the peptides and the ice-surface binding sites are the
      driving forces for the binding of AFPs to ice surfaces. We propose that there
      exists a concentration gradient of AFP from an ice-binding surface to the
      solution due to the affinity of ice surfaces to AFPs. This concentration gradient
      creates a dense layer of AFP in contact with the ice-binding surface, which
      depresses the local freezing point because of the colligative property, but not
      the Kelvin effect.

PMID- 12517133
TI  - Ultrabright supramolecular beacons based on the self-assembly of two-photon
      chromophores on metal nanoparticles.
AB  - Silver nanoparticles coated with a self-assembled layer of approximately 2500
      chromophoric alkylthiol ligands, that exhibit a huge per particle two-photon
      absorption cross section (2.7 x 10-45 cm4 s photon-1) and a high fluorescence
      quantum yield (0.33), are reported. Polyfunctionalized variants of these
      nanoparticles have been produced that show reasonable solubility in water/ethanol
      mixtures. By virtue of the large number of tethered chromophores, these particles
      act as strongly two-photon absorbing nanobeacons and may have applications in
      fluorescence imaging and sensing.

PMID- 12517135
TI  - Synthesis of sodium tantalate nanorods by alkalide reduction.
AB  - NaTaO3 nanorods were synthesized with high (>90%) yield by reduction of TaCl5
      with THF solutions of the alkalide K+(15C5)2Na-, followed by product annealing
      under dynamic vacuum at 250 and 600 degrees C. In addition to the nanorods, the
      product is comprised of 5-10% approximately 10-nm diameter spheroidal NaTaO3
      nanocrystals. The nanorods are generally longer than 500 nm, with some exceeding
      1 mum, and 10-100 nm wide, with aspect ratios that vary between 10 and 20:1.
      Select area electron diffraction patterns of individual nanorods indicate that
      each nanorod is a single crystal with its axis oriented in the [010] direction.

PMID- 12517136
TI  - Electrolytic synthesis of ammonia in molten salts under atmospheric pressure.
AB  - Ammonia was successfully synthesized by using a new electrochemical reaction with
      high current efficiency at atmospheric pressure and at lower temperatures than
      the Haber-Bosch process. In this method, nitride ion (N3-), which is produced by
      the reduction from nitrogen gas at the cathode, is anodically oxidized and reacts
      with hydrogen to produce ammonia at the anode.

PMID- 12517137
TI  - Layer-by-layer growth of metal-metal bonded supramolecular thin films and its use
      in the fabrication of lateral nanoscale devices.
AB  - Layer-by-layer self-assembly of metal-metal bonded supramolecules is demonstrated
      and utilized to fabricate lateral nanoelectronic devices. Mercaptoethylpyridine
      is used to bind to Au substrates and to template the sequential assembly of
      alternating layers of redox active dirhodium complexes [Rh2(DAniF)2]2(O2CCH2CO2)2
      (DAniF = N,N'-di-p-anisylformamidinate) and conjugated organic ligands trans-1,2
      bis(4-pyridyl)ethylene. Optical spectroscopy and atomic force microscopy show
      that the structure and composition of these thin films are similar to those found
      in tightly packed single crystals. Electrochemical studies of these films grown
      on Au substrates reveal a reversible oxidation wave at approximately 406 mV,
      corresponding to the one electron oxidation of the Rh24+ center. This directed
      assembly technique has been used to fabricate lateral nano-electronic devices in
      which the supramolecules span the channels. Tailoring the chemistry of the
      templating ligand enables assembly on desired surfaces and engineering the
      chemistry of the supramolecules' dimetal units and coordinating ligands may tune
      the device characteristics.

PMID- 12517138
TI  - A direct catalytic asymmetric mannich-type reaction to syn-amino alcohols.
AB  - The Mannich reaction is one of the most widely utilized chemical transformations
      for the construction of nitrogen-containing compounds. With the increasing
      occurrence of nitrogen in drugs and natural products, highly asymmetric variants
      of the Mannich reaction are desirable. In this communication, we report the
      application of our dinuclear zinc catalyst to a highly asymmetric Mannich-type
      reaction to generate syn 1,2-amino alcohols.

PMID- 12517139
TI  - Metal assembly in novel dendrimers with porphyrin cores.
AB  - A series of phenylazozmethine (DPA) dendrimers with a porphyrin core (PnH2) were
      synthesized by dehydration using TiCl4 from meso-tetrakis(4-aminophenyl)porphyrin
      and the DPA dendrons. The addition of SnCl2 to a dichloromethane/acetonitrile
      solution of dendritic cobalt porphyrin resulted in a stepwise spectral change. By
      using UV-vis spectroscopy to monitor the complexation of the P4CoIIICl until an
      equimolar amount of SnCl2 has been added, four changes in the position of the
      isosbestic point were observed during the addition of SnCl2. Titration results
      suggest that four different complexes are successively formed upon the SnCl2
      addition and that the complexation proceeds in, not a random, but a stepwise
      fashion from the core imines to the terminal imines of P4CoIIICl. The
      electrochemical study reveals that their dendrimers with Tb ion act as a
      multielectron mediator in CO2 reduction at high applied potential on the
      electrode.

PMID- 12517140
TI  - The PcoC copper resistance protein coordinates Cu(I) via novel S-methionine
      interactions.
AB  - The E. coli copper resistance protein PcoC enhances survival of a bacterium under
      conditions of extreme copper stress. This small protein has no cysteines, but
      does have an unusual methionine-rich sequence motif, suggesting that methionine
      ligation may be important in Cu binding. It is shown that PcoC binds both Cu(I)
      and Cu(II), in addition to binding Hg(II) and Ag(I). Previously crystallographic
      studies of PcoC had shown that the apo protein adopts a beta-barrel fold typical
      of that seen for blue-copper electron-transfer proteins. However, in contrast
      with electron-transfer proteins, where the Cu(I) and Cu(II) structures are nearly
      identical, X-ray absorption spectra show that the structures of the Cu site in
      reduced and oxidized PcoC are dramatically different. Cu(II) PcoC has a
      tetragonal Cu structure in which the Cu is coordinated to O or N ligands,
      including at least two histidine ligands. Cu(I) PcoC has a trigonal site with two
      methionine ligands. This is the first well-characterized example of a methionine
      rich protein Cu binding site, demonstrating a new type of biological Cu
      coordination chemistry.

PMID- 12517141
TI  - DNA detection and signal amplification via an engineered allosteric enzyme.
AB  - Rapid, sensitive, and sequence-specific DNA detection can be achieved in one step
      using an engineered intrasterically regulated enzyme. The semi-synthetic
      inhibitor-DNA-enzyme (IDE) construct (left) rests in the inactive state but upon
      exposure to a complementary DNA sequence undergoes a DNA hybridization-triggered
      allosteric enzyme activation (right). The ensuing rapid substrate turnover
      provides the built-in signal amplification mechanism for detecting approximately
      10 fmol DNA in less than 3 min under physiological conditions.

PMID- 12517142
TI  - DNA-based photonic logic gates: AND, NAND, and INHIBIT.
AB  - Conventional microprocessors use elementary logic gates to perform complex
      computational tasks. Mimicking such computational processes using purely
      molecular systems has been limited in most cases by the lack of design generality
      or potential addressability of existing molecular logic gates. Herein we report
      that by employing the universal recognition properties of DNA simple photonic
      logic gates can be created that are capable of AND, NAND, and INHIBIT logic
      operations.

PMID- 12517143
TI  - Discovery of novel dyes with absorption maxima at 1.1 microm.
AB  - During the process of developing organic molecules that match the wavelengths
      used in optical communications, we have discovered a new class of dyes, with
      absorption maxima at 1.1 mum, and clarified their molecular structures. The
      synthesis of this class of dyes was supposed to involve unexpected intramolecular
      tandem reactions, and the effect of alkyl substituents on such a synthesis was
      investigated. As a result, an effective alkyl-substituent structure for realizing
      a high synthetic yield and good solubility in organic solvents was found.
      Furthermore, thin films made of such a highly soluble dye were fabricated by
      solution-coating, and they exhibited a red-shifted absorption band with a maximum
      at approximately 1.3 mum, indicating the formation of J-like aggregates. The
      third-order nonlinear optical susceptibility chi(3) of these thin films at 1.3
      mum, which is the wavelength used in optical communications, was measured by the
      Z-scan technique. The magnitude of chi(3) reaches approximately 10-7 esu. These
      results suggest that the solution-coated thin films of this type of dye are
      potential materials for optical switching at 1.3 mum and for other nonlinear
      optical applications.

PMID- 12517144
TI  - Total synthesis of (+)-13-deoxytedanolide.
AB  - In this communication we describe the first total synthesis of (+)-13
      deoxytedanolide, an architecturally complex marine macrolide possessing
      significant antitumor activity. The cornerstone of the synthesis comprises a
      highly convergent dithiane coupling used to construct the carbon skeleton,
      followed by a novel use of the Evans-Tishchenko reduction to oxidize the C(1)
      aldehyde to an ester in the presence of the oxidatively labile dithiane.

PMID- 12517145
TI  - Alpha-helical-within-discotic columnar structures of a complex between
      poly(ethylene oxide)-block-poly(l-lysine) and a hexa-peri-hexabenzocoronene.
AB  - Poly(ethylene oxide)-block-poly(l-lysine) (PEO-PLL) was complexed with an
      amphiphilic hexa-peri-hexabenzocoronene (HBC). This produced a thermotropic
      liquid crystalline material (PEO-PLL-HBC), which was investigated by FTIR
      spectroscopy and differential scanning calorimetry as well as by wide- and small
      angle X-ray scattering. It was found that the poly(l-lysine) blocks form an alpha
      helical secondary structure. Each helix is surrounded symmetrically by six
      discotic columns of HBC, which gives an alpha-helical-within-discotic column
      structural entity. The dense packing of these entities produces hexagonal
      sublattices (formed by the columns) in the frame of a two-dimensional hexagonal
      lattice (formed by the helices). An order-order transition from a columnar
      structure Col1 to Col2 was found at 54 degrees C. The unit cell constants are
      5.75 nm (Col1) and 6.60 nm (Col2). The larger unit cell size of Col2 was
      explained by a higher intracolumnar order of the latter in which the packing
      distance of the disklike HBC cores is well-defined (0.353 nm). PEO-PLL-HBC
      combines essential features of liquid crystals with a basic structural element of
      proteins into a single material.

PMID- 12517146
TI  - Photoinduced electron-transfer along alpha-helical and coiled-coil
      metallopeptides.
AB  - A peptide-based electron-transfer system has been designed in which the specific
      positions of redox-active metal complexes appended to either an alpha-helix, or
      an alpha-helical coiled-coil, can be reversed to test the effect of the helix
      dipole in controlling photoinduced electron-transfer rates. Two 30-residue
      apopeptides were prepared having the following sequences: (I) Ac-K
      (IEALEGK)(ICALEGK)(IEALEHK)(IEALEGK)-G-amide, and (II) Ac-K-(IEALEGK)(IHALEGK)
      (IEALECK)(IEALEGK)-G-amide. Each apopeptide was reacted first with [Ru(bpy)2(phen
      ClAc)]2+, where bpy = 2,2'-bipyridine and phen-ClAc = 5-chloroacetamido-1,10
      phenanthroline, to attach the ruthenium polypyridyl center to the cysteine side
      chain of the polypeptide. The isolated products were then reacted with
      [Ru(NH3)5(H2O)]2+ to yield the binuclear electron-transfer metallopeptides ET-I
      and ET-II. In these systems, electron-transfer occurred from the photoexcited
      ruthenium polypyridyl donor to the pentammine ruthenium (III) acceptor such that
      the electron-transfer occurred toward the negative end of the helix dipole in ET
      I, and toward the positive end in ET-II. Circular dichroism spectroscopy showed
      that both peptides exist as dimeric alpha-helical coiled-coils in 100 mM
      phosphate buffer at pH 7, and as monomeric alpha-helices in the lower dielectric
      solvents 2,2,2-trifluoroethanol, and a 1:1 (v/v) mixture of CH2Cl2 and 2,2,2
      trifluoroethanol. The peptides were predominately (i.e., 65-72%) alpha-helical in
      these solvents. The emission lifetime behavior of ET-I was seen to be identical
      to that of ET-II in each of the three solvents: no evidence for directional
      electron-transfer rates was observed. Possible reasons for this behavior are
      discussed.

PMID- 12517147
TI  - Acetylcholinesterase complexed with bivalent ligands related to huperzine a:
      experimental evidence for species-dependent protein-ligand complementarity.
AB  - Acetylcholinesterase (AChE) inhibitors improve the cognitive abilities of
      Alzheimer patients. (-)-Huperzine A [(-)-HupA], an alkaloid isolated from the
      club moss, Huperzia serrata, is one such inhibitor, but the search for more
      potent and selective drugs continues. Recently, alkylene-linked dimers of 5-amino
      5,6,7,8-tetrahydroquinolinone (hupyridone, 1a), a fragment of HupA, were shown to
      serve as more potent inhibitors of AChE than (-)-HupA and monomeric 1a. We soaked
      two such dimers, (S,S)-(-)-bis(10)-hupyridone [(S,S)-(-)-2a] and (S,S)-(-)
      bis(12)-hupyridone [(S,S)-(-)-2b] containing, respectively, 10 and 12 methylenes
      in the spacer, into trigonal TcAChE crystals, and solved the X-ray structures of
      the resulting complexes using the difference Fourier technique, both to 2.15 A
      resolution. The structures revealed one HupA-like 1a unit bound to the "anionic"
      subsite of the active-site, near the bottom of the active-site gorge, adjacent to
      Trp84, as seen for the TcAChE/(-)-HupA complex, and the second 1a unit near
      Trp279 in the "peripheral" anionic site at the top of the gorge, both bivalent
      molecules thus spanning the active-site gorge. The results confirm that the
      increased affinity of the dimeric HupA analogues for AChE is conferred by binding
      to the two "anionic" sites of the enzyme. Inhibition data show that (-)-2a binds
      to TcAChE approximately 6-7- and > 170-fold more tightly than (-)-2b and (-)
      HupA, respectively. In contrast, previous data for rat AChE show that (-)-2b
      binds approximately 3- and approximately 2-fold more tightly than (-)-2a and (-)
      HupA, respectively. Structural comparison of TcAChE with rat AChE, as represented
      by the closely related mouse AChE structure (1maa.pdb), reveals a narrower gorge
      for rat AChE, a perpendicular alignment of the Tyr337 ring to the gorge axis, and
      its conformational rigidity, as a result of hydrogen bonding between its hydroxyl
      group and that of Tyr341, relative to TcAChE Phe330. These structural differences
      in the active-site gorge explain the switch in inhibitory potency of (-)-2a and
      2b and the larger dimer/(-)-HupA potency ratios observed for TcAChE relative to
      rat AChE. The results offer new insights into factors affecting protein-ligand
      complementarity within the gorge and should assist the further development of
      improved AChE inhibitors.

PMID- 12517148
TI  - Nanotube-vesicle networks with functionalized membranes and interiors.
AB  - We describe nanotube-vesicle networks with reconstituted membrane protein from
      cells and with interior activity defined by an injection of microparticles or
      molecular probes. The functionality of a membrane protein after reconstitution
      was verified by single-channel ion conductance measurements in excised inside-out
      patches from the vesicle membranes. The distribution of protein, determined by
      fluorescence detection, in the network membrane was homogeneous and could diffuse
      via a nanotube connecting two vesicles. We also show how injecting small
      unilamellar protein-containing vesicles can differentiate the contents of
      individual containers in a network. The combination of membrane activity and
      interior activity was demonstrated by ionophore-assisted accumulation, and
      internal Calcium Green-mediated detection, of Ca2+ within a single network
      container. This system can model a variety of biological functions and complex
      biological multicompartment structures and might serve as a platform for
      constructing complex sensor and computational devices.

PMID- 12517149
TI  - Assay for the enantiomeric analysis of [2H1]-fluoroacetic acid: insight into the
      stereochemical course of fluorination during fluorometabolite biosynthesis in
      streptomyces cattleya.
AB  - A sensitive method for the configurational analysis of (R)- and (S)-[2H1]
      fluoroacetate has been developed using 2H[1H]-NMR in a chiral liquid crystalline
      solvent. This has enabled biosynthetic experiments to be conducted which reveal
      stereochemical details on biological fluorination occurring during the
      biosynthesis of fluoroacetate and 4-fluorothreonine in the bacterium Streptomyces
      cattleya. In particular, feeding experiments to S. cattleya with isotopically
      labeled (1R, 2R)- and (1S, 2R)-[1-2H1]-glycerol 3d and 3e and [2,3-2H(4)]
      succinate 4a gave rise to samples of enantiomerically enriched [2-2H1]
      fluoroacetates 1a. The predominant enantiomer resulting from each experiment
      suggests that the stereochemical course of biological fluorination takes place
      with an overall retention of configuration between a glycolytic intermediate and
      fluoroacetate 1. Consequently, this outcome suggests that the stereochemical
      course of the recently identified fluorinase enzyme which mediates a reaction
      between fluoride ion and S-adenosyl-l-methionine (SAM), occurs with an inversion
      of configuration.

PMID- 12517150
TI  - Stability of cyclic beta-hairpins: asymmetric contributions from side chains of a
      hydrogen-bonded cross-strand residue pair.
AB  - Amino acid structural propensities measured in "host-guest" model studies are
      often used in protein structure prediction or to choose appropriate residues in
      de novo protein design. While this concept has proven useful for helical
      structures, it is more difficult to apply successfully to beta-sheets. We have
      developed a cyclic beta-hairpin scaffold as a host for measurement of individual
      residue contributions to hairpin structural stability. Previously, we have
      characterized substitutions in non-backbone-hydrogen-bonded strand sites;
      relative stability differences measured in the cyclic host are highly predictive
      of changes in folding free energy for linear beta-hairpin peptides. Here, we
      examine the hydrogen-bonded strand positions of our host. Surprisingly, we find a
      large favorable contribution to stability from a valine (or isoleucine)
      substitution immediately preceding the C-terminal cysteine of the host peptide,
      but not at the cross-strand position of the host or in either strand of a folded
      linear beta-hairpin (trpzip peptide). Further substitutions in the peptides and
      NMR structural analysis indicate that the stabilizing effect of valine is general
      for CX(8)C cyclic hairpins and cannot be explained by particular side-chain-side
      chain interactions. Instead, a localized decrease in twist of the peptide
      backbone on the N-terminal side of the cysteine allows the valine side chain to
      adopt a unique conformation that decreases the solvent accessibility of the
      peptide backbone. The conformation differs from the highly twisted (coiled)
      conformation of the trpzip hairpins and is more typical of conformations present
      in multistranded beta-sheets. This unexpected structural fine-tuning may explain
      why cyclic hairpins selected from phage-displayed libraries often have valine in
      the same position, preceding the C-terminal cysteine. It also emphasizes the
      diversity of structures accessible to beta-strands and the importance of
      considering not only "beta-propensity", but also hydrogen-bonding pattern and
      strand twist, when designing beta structures. Finally, we observe correlated,
      cooperative stabilization from side-chain substitutions on opposite faces of the
      hairpin. This suggests that cooperative folding in beta-hairpins and other small
      beta-structures is driven by cooperative strand-strand association.

PMID- 12517151
TI  - The role of amine in the mechanism of pentathiepin (polysulfur) antitumor agents.
AB  - A computational and experimental study is presented, which provides the first
      evidence that amine has an opportunity to engage in bonding with pentathiepin to
      promote its decomposition. The study provides mechanistic insight into the
      process that gives rise to pentathiepin biological activity. Primary or secondary
      amine will allow for an intramolecular addition to the pentathiepin ring at the
      nearest sulfur (S1). In contrast, tertiary amine adds reversibly to S1, because
      nitrogen cannot lose its positive charge by deprotonation. This precludes the
      amine promotion step. An energetically low-lying process is characterized,
      corresponding to S3-loss triggered by nucleophilic activation with a primary or
      secondary amine. Pentathiepin desulfurization via S3-unit transfer is supported
      by a trapping study with norbornene. That the amine may confer an enhanced
      reactivity in the natural products varacin, 1, and lissoclinotoxin A, 2, adds to
      the understanding of the pathway for pentathiepin activation and may provide new
      design concepts that have potential applications for this class of biocides.

PMID- 12517152
TI  - Using nitrile-derivatized amino acids as infrared probes of local environment.
AB  - It is well-known that the C=N stretching vibration in acetonitrile is sensitive
      to solvent. Therefore, we proposed in this contribution to use this vibrational
      mode to report local environment of a particular amino acid in proteins or local
      environmental changes upon binding or folding. We have studied the solvent
      induced frequency shift of two nitrile-derivatized amino acids, which are, AlaCN
      and PheCN, in H(2)O and tetrahydrofuran (THF), respectively. Here, THF was used
      to approximate a protein's hydrophobic interior because of its low dielectric
      constant. As expected, the C=N stretching vibrations of both AlaCN and PheCN
      shift as much as approximately 10 cm(-1) toward higher frequency when THF was
      replaced with H2O, indicative of the sensitivity of this vibration to solvation.
      To further test the utility of nitrile-derivatized amino acids as probes of the
      environment within a peptide, we have studied the binding between calmodulin
      (CaM) and a peptide from the CaM binding domain of skeletal muscle myosin light
      chain kinase (MLCK(579-595)), which contains a single PheCN. MLCK(579-595) binds
      to CaM in a helical conformation. When the PheCN was substituted on the polar
      side of the helix, which was partially exposed to water, the C=N stretching
      vibration is similar to that of PheCN in water. In constrast, when PheCN is
      introduced at a site that becomes buried in the interior of the protein, the C=N
      stretch is similar to that of PheCN in THF. Together, these results suggest that
      the C=N stretching vibration of nitrile-derivatized amino acids can indeed be
      used as local internal environmental markers, especially for protein
      conformational studies.

PMID- 12517153
TI  - An efficient RNA-cleaving DNA enzyme that synchronizes catalysis with
      fluorescence signaling.
AB  - DNA enzymes are single-stranded DNA molecules with catalytic capabilities that
      are isolated from random-sequence DNA libraries by "in vitro selection". This new
      class of catalytic biomolecules has the potential of being used as unique
      molecular tools in a variety of innovative applications. Here we describe the
      creation and characterization of an RNA-cleaving autocatalytic DNA, DEC22-18,
      that uniquely links chemical catalysis with real-time fluorescence signaling
      capability in the same molecule. A trans-acting DNA molecule, DET22-18, was also
      developed from DEC22-18 that behaves as a true enzyme with a k(cat) of
      approximately 7 min(-1)-a rate constant that is the second largest ever reported
      for a DNA enzyme. It cleaves a chimeric RNA/DNA substrate at the lone RNA linkage
      surrounded by a closely spaced fluorophore-quencher pair-a unique structure that
      permits the synchronization of the chemical cleavage with fluorescence signaling.
      DET22-18 has a stem-loop structure and can be conjugated with DNA aptamers to
      form allosteric deoxyribozyme biosensors.

PMID- 12517154
TI  - A new chiral probe for sulfate anion: UV, CD, fluorescence, and NMR spectral
      studies of 1:1 and 2:1 complex formation and structure of chiral guanidinium-p
      dimethylaminobenzoate conjugate with sulfate anion.
AB  - A new chiral chromophoric host 1, possessing a 4-(N,N-dimethylamino)benzoate
      (DMAB) group tethered to a chiral bicyclic guanidinium subunit, was synthesized
      and applied to the probe for sulfate anion. Host 1 showed typical successive 1:1
      and 2:1 host:guest complexation behavior toward the divalent sulfate anion, as
      revealed by UV-vis, CD, fluorescence, and 1H NMR spectroscopic studies. The DMAB
      chromophore was shown to be a sensitive CD spectral probe for assessing not only
      the complexation behavior but also complex stoichiometry and structure. The
      stepwise 1:1 and 2:1 complexation constants (K1 and K2) were determined as 1.53 x
      10(6) and 4.84 x 10(4) M(-1), respectively, by NMR titration in CD3CN. The CD
      exciton chirality method allowed us to determine the chiral sense (spatial
      arrangement) of the two DMAB moieties in the 2:1 complex as negative
      (counterclockwise). The dual fluorescence behavior of DMAB was employed for
      elucidating the role of the countercation upon complexation of host 1 with
      sulfates possessing lipophilic countercation(s) such as tetrabutylammonium.

PMID- 12517155
TI  - Opening of tartrate acetals using dialkylboron bromide: evidence for
      stereoselectivity downstream from ring fission.
AB  - Johnson-type acetals derived from dimethyl tartrate give, after opening with
      Me(2)BBr and cuprate displacement, secondary alcohols with high
      diastereoselectivity (>30:1). The mechanism proposed for the induction of
      diastereoselectivity is downstream from the ring fission. It implies a direct
      participation of the Lewis acid as a source of nucleophile and the stereospecific
      transformation of the resulting bromo acetal through an invertive and temperature
      dependent process. The acetals are prepared by reaction of the desired aldehyde
      with dimethyl tartrate. Removal of the auxiliary is accomplished through SmI(2)
      reduction or by an addition-elimination protocol using methoxide.

PMID- 12517156
TI  - Attaching perylene dyes to polyfluorene: three simple, efficient methods for
      facile color tuning of light-emitting polymers.
AB  - The emission color of fluorene-based polymers can be facilely tuned across the
      whole visible spectrum by copolymerization with perylene dyes. Methods are
      demonstrated for incorporation of the dyes in the polymer mainchain, at the chain
      termini, or as side chains. Efficient energy transfer causes the emission to come
      solely from the dye units. Efficient LEDs have been made from the copolymers with
      dyes in the mainchain.

PMID- 12517157
TI  - Supramolecular recognition. Terpyridyl palladium and platinum molecular clefts
      and their association with planar platinum complexes.
AB  - Molecular receptors, consisting of either two parallel cofacially disposed
      terpyridyl-Pd-Cl+ or terpyridyl-Pt-Cl+ units, are described. Concerted rotation
      of these units about the molecular spacer can alter their separation between 6.4
      and 7.2 A to accommodate the dimensions of molecular guests. Neutral and anionic
      planar complexes of platinum(II) were investigated as guests to determine if
      metal-metal interaction between the host and guest metals could stabilize host
      guest association. With a neutral guest, it was found that host-guest formation
      is signaled by a color change from light yellow to deep red. For one of the
      anionic guests, a visible absorption band appears upon host-guest formation with
      the platinum receptor that is ascribed to transitions associated with a Pt-Pt
      interaction. The association constants found for the neutral guest with the
      palladium and platinum receptors are large, suggesting that metal-metal
      interaction contributes to the molecular recognition. The structures of the host
      (neutral)guest complexes in solution have been determined by 1H NOESY spectra. A
      crystal structure of the platinum host-(neutral)guest complex is the same as that
      found in solution and confirms the presence of a Pt-Pt interaction. Temperature
      dependent (195)Pt NMR spectra in solution provide a quantitative estimate of the
      conformational interconversions of the free platinum receptor.

PMID- 12517158
TI  - Highly stable self-assembly in water: ion pair driven dimerization of a
      guanidiniocarbonyl pyrrole carboxylate zwitterion.
AB  - The synthesis of a novel water-soluble guanidiniocarbonyl pyrrole carboxylate
      zwitterion 2 is described, and its self-association in aqueous solutions is
      studied. Zwitterion 2 forms extremely stable 1:1 dimers which are held together
      by an extensive hydrogen bonding network in combination with two mutual
      interacting ion pairs as could be shown by ESI MS and X-ray structure
      determination. NMR dilution studies in different highly polar solvents showed
      that dimerization is fast on the NMR time scale with association constants
      ranging from an estimated 10(10) M(-1) in DMSO to a surprisingly high 170 M(-1)
      in water. Hence, zwitterion 2 belongs to the most efficient self-assembling
      systems solely on the basis of electrostatic interactions reported so far.
      Furthermore, an amidopyridine pyrrole carboxylic acid 10 was developed as a
      neutral analogue of zwitterion 2, which also dimerizes with an essentially
      identical hydrogen bonding pattern (according to ESI MS and X-ray structure
      determination) but lacking the ionic interactions. NMR binding studies
      demonstrated that the solely hydrogen-bonded neutral dimer of 10 is stable only
      in organic solvents of low polarity (K > 10(4) M(-1) in CDCl3 but <10 M(-1) in 5%
      DMSO in CDCl3). The comparison of both systems impressively underlines the
      importance of ion pair interactions for stable self-association of such H-bonded
      binding motifs in water.

PMID- 12517159
TI  - Photothermal patterning of microgel/gold nanoparticle composite colloidal
      crystals.
AB  - We present a new method for laser direct writing in self-assembled hydrogel
      microparticle colloidal crystals via photothermal excitation of co-assembled
      colloidal Au particles. Close-packed colloidal crystals are assembled from
      approximately 224 nm diameter, thermoresponsive, poly-N-isopropylacrylamide
      hydrogel microparticles (microgels); these crystals display sharp Bragg
      diffraction peaks in the mid-visible region of the spectrum due to the periodic
      dielectric function of the assembly. Raising the temperature of the crystal above
      the characteristic volume phase transition temperature of the microgel particles
      results in a reversible melting of the crystalline material due to the particle
      based deswelling event. This transition can be used either to anneal defects from
      the crystalline material or to controllably and reversibly convert the assembly
      from the colored, crystalline state to a nondiffracting glassy material. Crystal
      to-glass transitions are similarly accomplished via photothermal excitation when
      16 nm diameter colloidal Au particles are co-assembled with the responsive
      microgels. Excitation of the colloidal Au plasmon absorption with a frequency
      doubled Nd:YAG laser (lambda = 532 nm) results in optically directed conversion
      of either glasses to crystals or crystals to glasses, depending on the initial
      state of the assembly and the illumination time. These results represent a
      fundamentally new method for the patterning of self-assembled photonic materials.

PMID- 12517161
TI  - Control of charge recombination dynamics in dye sensitized solar cells by the use
      of conformally deposited metal oxide blocking layers.
AB  - We report herein a methodology for conformally coating nanocrystalline TiO2 films
      with a thin overlayer of a second metal oxide. SiO2, Al2O3, and ZrO2 overlayers
      were fabricated by dipping mesoporous, nanocrystalline TiO2 films in organic
      solutions of their respective alkoxides, followed by sintering at 435 degrees C.
      These three metal oxide overlayers are shown in all cases to act as barrier
      layers for interfacial electron transfer processes. However, experimental
      measurements of film electron density and interfacial charge recombination
      dynamics under applied negative bias were vary significantly for the overlayers.
      A good correlation was observed between these observations and the point of zero
      charge of the different metal oxides. On this basis, it is found that the most
      basic overlayer coating, Al2O3 (pzc = 9.2), is optimal for retarding interfacial
      recombination losses under negative applied bias. These observations show good
      correlation with current/voltage analyses of dye sensitized solar cell fabricated
      from these films, with the Al2O3 resulting in an increase in V(oc) of up to 50 mV
      and a 35% improvement in overall device efficiency. These observations are
      discussed and compared with an alternative TiCl4 posttreatment of nanocrystalline
      TiO2 films with regard to optimizing device efficiency.

PMID- 12517160
TI  - Spectroscopic and electronic structure studies of the diamagnetic side-on CuII
      superoxo complex Cu(O2)[HB(3-R-5-iPrpz)3]: antiferromagnetic coupling versus
      covalent delocalization.
AB  - Magnetic, vibrational, and optical techniques are combined with density
      functional calculations to elucidate the electronic structure of the diamagnetic
      mononuclear side-on CuII-superoxo complex. The electronic nature of its lowest
      singlet/triplet states and the ground-state diamagnetism are explored. The
      triplet state is found to involve the interaction between the Cu xy and the
      superoxide pi v * orbitals, which are orthogonal to each other. The singlet
      ground state involves the interaction between the Cu xy and the in-plane
      superoxide pi v * orbitals, which have a large overlap and thus strong bonding.
      The ground-state singlet/triplet states are therefore fundamentally different in
      orbital origin and not appropriately described by an exchange model. The ground
      state singlet is highly delocalized with no spin polarization.

PMID- 12517162
TI  - Ultrafast processes in bimetallic dyads with extended aromatic bridges. Energy
      and electron transfer pathways in tetrapyridophenazine-bridged complexes.
AB  - The energy and electron transfer processes taking place in binuclear polypyridine
      complexes of ruthenium and osmium based on the tetrapyrido[3,2-a:2',3'-c:3' ',2'
      '-h:2' "-3' "-j]phenazine bridging ligand (tpphz) have been investigated by
      ultrafast absorption spectroscopy. In the binuclear complexes, each chromophore
      is characterized by two spectrally distinguishable metal-to-ligand charge
      transfer (MLCT) excited states: MLCT1 (with promoted electron mainly localized on
      the bpy-like portion of tpphz, higher energy) and MLCT0 (with promoted electron
      mainly localized on the pyrazine-like portion of tpphz, lower energy). In the
      homodinuclear complexes Ru(II)-Ru(II) and Os(II)-Os(II), MLCT1 --> MLCT0
      relaxation (intraligand electron transfer) is observed, with strongly solvent
      dependent kinetics (ca. 10(-10) s in CH2Cl2, ca. 10(-12) s in CH3CN). In the
      heterodinuclear Ru(II)-Os(II) complex, *Ru(II)-Os(II) --> Ru(II)-Os(II) energy
      transfer takes place by two different sequences of time-resolved processes,
      depending on the solvent: (a) in CH2Cl2, ruthenium-to-osmium energy transfer at
      the MLCT1 level followed by MLCT1 --> MLCT0 relaxation in the osmium chromophore,
      (b) in CH3CN, MLCT1 --> MLCT0 relaxation in the ruthenium chromophore followed by
      osmium-to-ruthenium metal-to-metal electron transfer. In the mixed-valence Ru(II)
      Os(III) species, the *Ru(II)-Os(III) --> Ru(III)-Os(II) electron transfer
      quenching is found to proceed by two consecutive steps in CH3CN: intraligand
      electron transfer followed by ligand-to-metal electron transfer. On a longer time
      scale, charge recombination leads back to the ground state. Altogether, the
      results show that the tpphz bridge plays an active mechanistic role in these
      systems, efficiently mediating the transfer processes with its electronic levels.

PMID- 12517163
TI  - Perhydrocarbyl ReVII complexes: comparison of molecular and surface complexes.
AB  - The molecular complex [Re(=CtBu)(=CHtBu)(CH2tBu)2] 1 reacts with a silica
      partially dehydroxylated at 700 degrees C to give syn-2,
      [(=SiO)Re(=CtBu)(=CHtBu)(CH2tBu)], as a single isomer according to mass-balance
      analysis, IR, and solid-state NMR spectroscopy. 1D and 2D solid-state NMR (HETCOR
      and long-range HETCOR) on a 13C-labeled-2 has allowed us to observe the chemical
      shifts of all carbons (including those that are not labeled) and ascertain their
      assignments. Moreover, EXAFS data are consistent with the presence of two carbons
      at a relatively short distance (1.79 A), which cannot be deconvoluted, but which
      are consistent with the presence of alkylidene and alkylidyne carbons along with
      two other first neighbors at a longer distance (2.01 A), the alkyl carbon and the
      O atom by which the Re is attached to the surface. Moreover, the data also
      suggest the presence of a siloxane bridge of the silica surface at 2.4 A in the
      coordination sphere of the Re center. Thermal and photochemical treatment allow
      us to observe the anti isomer, which was also fully characterized by 1D and 2D
      solid-state NMR. This behavior parallels the reactivity of molecular Re
      complexes, and their respective 1H and 13C chemical shifts match those of the
      corresponding molecular analogues syn- and anti-2m and n. Finally, the grafting
      of 1 onto silica involves the reaction of both the alkyl and the alkylidene
      ligand with an equiprobability, leaving the alkylidyne as a spectator ligand.
      Noteworthy is the formation of 2 [(=SiO)Re(=CtBu)(=CHtBu)(CH2tBu)], rather than
      the corresponding trisneopentyl-neopentylidyne Re complex, monografted on silica,
      [(=SiO)Re(=CtBu)(CH2tBu)3], which would have been expected from the reactivity of
      1 with various molecular Bronsted acids and which also suggests that a proximal
      siloxane bridge forces the alpha-H abstraction process, leading to syn-2a.

PMID- 12517164
TI  - Measurements of electron-transfer rates of charge-storage molecular monolayers on
      Si(100). Toward hybrid molecular/semiconductor information storage devices.
AB  - Redox kinetics were measured for two electroactive molecules attached to Si(100)
      surfaces, a ferrocene (Fc-BzOH) and a Zn(II) trimesitylporphyrin (Por-BzOH). Each
      molecule was derivatized with a benzyl alcohol linker for attachment to the Si
      surface via the formation of a Si-O bond. A complete protocol was developed for
      the preparation of stable Si(100) surfaces derivatized with the electroactive
      molecules. The redox-kinetic measurements were performed on the resulting Fc-BzOH
      and Por-BzOH monolayers to probe (1) the rate of electron transfer (k0) for
      oxidation in the presence of applied potentials and (2) the rate of charge
      dissipation after the applied potential is disconnected (in the form of a charge
      retention half-life t1/2). The k0 values for the two types of monolayers were
      found to be similar to one another as were the t1/2 values. Perhaps more
      importantly, the electron-transfer rates for both the Fc-BzOH and the Por-BzOH
      monolayers differ from the charge-dissipation rates by approximately 6 orders of
      magnitude and are strongly dependent on the surface concentration of the
      electroactive species. For the Por-BzOH monolayers on Si(100), the k0 and t1/2
      values and their trends as a function of surface coverage were determined to be
      similar to those previously measured for the analogous thiol-derivatized molecule
      assembled on Au(111). In contrast, the Fc-BzOH monolayers on Si(100) were found
      to exhibit much slower electron-transfer and charge-dissipation rates than those
      in the corresponding thiol-Au(111) case. Two alternative hypotheses are advanced
      to explain both the diminution in rates with increased surface coverage and the
      contrasting behavior with the analogous thiols on Au, one based on space-charge
      effects at the monolayer-solution interface, and a second relying on changes in
      distance of the redox centers from the surface as modulated by the orientation of
      the linking chains. Collectively, the ability to prepare and study stable,
      electroactive molecular media on Si(100) is likely to be key in the development
      of hybrid molecular/semiconductor devices.

PMID- 12517165
TI  - Activation of alkenes and H2 by [Fe]-H2ase model complexes.
AB  - The established ability of the Fe(II) bridging hydride species (micro-H)(micro
      pdt)[Fe(CO)2(PMe3)]2+, 1-H+, to take-up and heterolytically activate dihydrogen,
      resulting in H/D scrambling of H2/D2 and H2/D2O mixtures (Zhao et al. Inorg.
      Chem. 2002, 41, 3917) has prompted a study of simultaneous alkene/H2 activation
      by such [Fe]H2ase model complexes. That the required photolysis produced an open
      site was substantiated by substitution of CO in 1-H+ by CH3CN with formation of
      structurally characterized [(micro-H)(micro
      pdt)[Fe(CO)2(PMe3)][Fe(CO)(CH3CN)(PMe3)]]+[PF6]-. Under similar photolytic
      conditions, H/D exchange reactions between D2 and terminal alkenes (ethylene,
      propene and 1-butene), but not bulkier alkenes such as 2-butene or cyclohexene,
      were catalyzed by 1-H+ and the edt (SCH2CH2S) analogue, 2-H+. Substantial
      regioselectivity for H/D exchange at the internal vinylic hydrogen was observed.
      The extent to which the olefins were deuterium enriched vs deuterated was
      catalyst dependent. The stabilizing effect of the binuclear chelating ligands,
      SCH2CH2CH2S, pdt, and SCH2CH2S, edt, is required for the activity of binuclear
      catalysts, as the mono-dentate micro-SEt analogue decomposed to inactive products
      under the photolytic conditions of the catalysis. Reactions of 1 and 2 with
      EtOSO2CF3 yielded the S-alkylated products, [(micro
      SCH2CH2CH2SEt)[Fe(CO)2(PMe3)]2]+[SO3CF3]- (1-Et+), and 2-Et+, rather than micro
      C2H5 analogues to the micro-H of 1-H+. The stability and lack of reactivity
      toward H2 of 1-Et+ and 2-Et+, indicates they are not on the reaction path of the
      olefin/D2 H/D exchange process. A mechanism with olefin binding to an open site
      created by CO loss and formation of an Fe-(CH2CHDR) intermediate is indicated. A
      likely role of a binuclear chelate effect is implicated for the unique S-XXX-S
      cofactor in the active site of [Fe]H2ase.

PMID- 12517166
TI  - Sonochemical production of fluorescent and phosphorescent latex particles.
AB  - A novel method for producing nanosized polymer latex particles doped with
      fluorescent and phosphorescent solutes is described. Methyl methacrylate monomer
      (10 wt %) containing either pyrene, 4-dicyanomethylene-2-methyl-6-(p
      dimethylaminostyryl)-4H-pyran (DMDP), or 1-bromonaphthalene was ultrasonically
      dispersed in water and simultaneously polymerized to produce approximately 60 nm
      diameter latex particles. A fluorescence spectroscopic examination of the latex
      dispersion containing either pyrene or DMDP showed that the solutes were not
      covalently bound to the polymer and that they were embedded in a highly viscous
      environment possessing a low polarity (dielectric constant on the order of 2).
      The fluorescence lifetime of the pyrene in the core of the poly(MMA) latex was
      found to be 520 ns, irrespective of the oxygen concentration in the dispersion.
      Room-temperature phosphorescence was observed from 1-bromonaphthalene, with a
      lifetime of 2.0 ms in an argon atmosphere. In the presence of air,
      phosphorescence was still observable although with a partially reduced emission
      intensity.

PMID- 12517167
TI  - Direct electrochemistry of a bacterial sulfite dehydrogenase.
AB  - Sulfite dehydrogenase from Starkeya novella is an alphabeta heterodimer
      comprising a 40.6 kDa subunit (containing the Mo cofactor) and a smaller 8.8 kDa
      heme c subunit. The enzyme catalyses the oxidation of sulfite to sulfate with the
      natural electron acceptor being cytochrome c550. Its catalytic mechanism is
      thought to resemble that found in eukaryotic sulfite oxidases. Using protein film
      voltammetry and redox potentiometry, we have identified both Mo- and heme
      centered redox responses from the enzyme immobilized on a pyrolytic graphite
      working electrode: E m,8 (Fe III/II) +177 mV; E m,8 (Mo VI/V) +211 mV and E m,8
      (Mo V/IV) -118 mV vs NHE; Upon addition of sulfite to the electrochemical cell a
      steady-state voltammogram is observed and an apparent Michaelis constant (Km) of
      26(1) microM was determined for the enzyme immobilized on the working electrode
      surface, which is comparable with the value obtained from solution assays.

PMID- 12517168
TI  - Intermolecular coupling in nanometric domains of light-harvesting dendrimer films
      studied by photoluminescence near-field scanning optical microscopy (PL NSOM).
AB  - Near-field scanning optical microscopy (NSOM) has been used to investigate the
      photophysical characteristics of first- to fourth-generation (G1 to G4) light
      harvesting dendrimer thin films containing coumarin-343 and coumarin-2 as the
      core and peripheral chromophores, respectively. Thin film photoluminescence (PL)
      spectra exhibit a significant red shift in the lower generations (G1, G2, and G3)
      as compared to their respective solution PL spectra, implying the formation of
      excimers. Spatially resolved PL NSOM images exhibit pronounced nanoscopic domains
      in G1, which become more homogeneous in higher generations due to site-isolation
      of the core chromophore. G4 exhibits complete site-isolation for these light
      harvesting dendrimer films.

PMID- 12517169
TI  - Accurate first principles prediction of 17O NMR parameters in SiO2: assignment of
      the zeolite ferrierite spectrum.
AB  - 17O NMR parameters, both the chemical shifts and the quadrupolar parameters, are
      calculated for SiO2 polymorphs using density functional theory with the
      generalized gradient-corrected PBE functional. The gauge including projector
      augmented wave (GIPAW) method (Pickard, C. J.; Mauri, F. Phys. Rev. B2001, 63,
      245101) ensures the reproduction of all electron results while using
      computationally efficient pseudopotentials. The use of plane-waves permits fully
      converged calculations to be performed on structures containing 144 atoms in the
      unit cell, without the need to resort to the cluster approximation. The
      calculated NMR parameters of cristobalite, quartz, coesite, and faujasite are in
      excellent agreement with experimental data. This demonstrates that density
      functional theory is able to reproduce with high accuracy the 17O NMR parameters
      in SiO2 systems. This precision is used to assign the spectrum of the zeolite
      ferrierite. The data calculated for SiO2 are used to confirm that no simple
      correlation between the chemical shift and Cq NMR parameters and Si-O-Si angle
      exists, emphasizing the importance of predictive theories in this field.

PMID- 12517170
TI  - Ultrafast electronic relaxation and coherent vibrational oscillation of strongly
      coupled gold nanoparticle aggregates.
AB  - We report the first direct observation of the ultrafast electronic relaxation and
      coherent vibrational oscillation of strongly interacting gold nanoparticle
      aggregates measured by femtosecond laser spectroscopy. The electronic relaxation,
      reflected as a fast decay component with a time constant of 1.5-2.5 ps, becomes
      faster with decreasing pump power, similar to earlier observations of isolated
      gold nanoparticles. Surprisingly, periodic oscillations have been observed in the
      transient absorption/bleach signal and have been attributed to the coherent
      vibrational excitation of the gold nanoparticle aggregates. The oscillation
      period has been found to depend on the probe wavelength. As the probe wavelength
      is varied from 720 to 850 nm, the period changes from 37 to 55 ps. This suggests
      that the broad extended plasmon band (EPB) contains contributions from gold
      nanoparticle aggregates with different sizes and/or different fractal structures.
      Each of the different probe wavelengths therefore interrogates one subset of the
      aggregates with similar size or structure. Interestingly, the observed
      oscillation period for a given aggregate size determined by dynamic light
      scattering is longer than that predicted based on a elastic sphere model. One
      possible explanation is that the actual size of the aggregates is larger than
      what was observed from dynamic light scattering. An alternative, perhaps more
      likely, explanation is that the vibration of the aggregates is "softer" than that
      of hard spherical gold nanoparticles possibly because the longitudinal speed of
      sound is lower in the aggregates than in bulk gold. Persistent spectral hole
      burning was performed and yielded a hole in the nanoparticle aggregate's extended
      plasmon band, further supporting that the near-IR band is composed of absorption
      subbands from differently sized/structured aggregates.

PMID- 12517171
TI  - Fabrication of complex three-dimensional microchannel systems in PDMS.
AB  - This paper describes a method for fabricating three-dimensional (3D) microfluidic
      channel systems in poly(dimethylsiloxane) (PDMS) with complex topologies and
      geometries that include a knot, a spiral channel, a "basketweave" of channels, a
      chaotic advective mixer, a system with "braided" channels, and a 3D grid of
      channels. Pseudo-3D channels, which are topologically equivalent to planar
      channels, are generated by bending corresponding planar channels in PDMS out of
      the plane into 3D shapes. True 3D channel systems are formed on the basis of the
      strategy of decomposing these complex networks into substructures that are planar
      or pseudo-3D. A methodology is developed that connects these planar and/or pseudo
      3D structures to generate PDMS channel systems with the original 3D geometry.
      This technique of joining separate channel structures can also be used to create
      channel systems in PDMS over large areas by connecting features on different
      substrates. The channels can be used as templates to form 3D structures in other
      materials.

PMID- 12517172
TI  - Probing the configurational space of a metalloprotein core: an ab initio
      molecular dynamics study of Duo Ferro 1 binuclear Zn cofactor.
AB  - We present three theoretical models of various degree of completeness to explore
      the chemical phase space available to the Glu4His2Zn2 cofactor found in the four
      helix bundle of de novo designed metalloprotein Duo Ferro 1. We have found that
      the planewave DFT geometry optimization of 94-atom Model I, which contains both
      the protein scaffold constraints as well as the second shell hydrogen bonding
      network, reproduces the crystal structure bonding with remarkable accuracy (0.34
      A). Surprisingly, the geometry optimization of 66-atom Model II (lacking the
      second shell hydrogen bonding) and 48-atom Model III (being also free of the
      protein scaffold constraints) still result in the fidelity with the
      crystallographic structure (RMSDs 0.29 and 0.34 A, respectively). To examine
      whether these structures are close to the global minimum as well as to
      investigate various conformational transitions to which the di-Zn cofactor may be
      susceptible to, we have carried out a 10 ps Car-Parrinello Molecular Dynamics
      (CPMD) simulation of Model III. We suggest that weak hydrogen bonds between
      imidazole hydrogens and carboxylate oxygens modulate the dynamical behavior of
      the system. One part of the molecule was found to be rigid due to the particular
      H(imidazole)-O(carboxylate) interaction restricting both the motion of the
      imidazole ring as well as the terminal carboxylate conformational mobility. The
      second half of the system was very flexible demonstrating a coupling of a
      transient formation of H(imidazole)-O(carboxylate) bonds with the spinning of the
      imidazole ring and syn-anti isomerization of the terminal carboxylate group. In
      addition, two low-energy snapshots from the 10 ps CPMD run were quenched, and
      their geometries were optimized, leading to two new isomers 48 kJ/mol lower in
      energy than the one associated with the crystal structure. We suggest that
      periodic quenching of the CPMD simulation snapshots of a minimalist model may be
      used as an efficient method to generate a large number of competitive local
      minima, which may be consequently pruned by imposing the protein scaffold
      constraints as well as further tuned by the second shell hydrogen bonding
      network.

PMID- 12517173
TI  - Internal degrees of freedom, structural motifs, and conformational energetics of
      the 5'-deoxyadenosyl radical: implications for function in adenosylcobalamin
      dependent enzymes. A computational study.
AB  - The potential energy surface of the free 5'-deoxyadenosyl radical in the gas
      phase is explored using density functional and second-order Moller-Plesset
      perturbation theories with 6-31G(d) and 6-31++G(d,p) basis sets and interpreted
      in terms of attractive and repulsive interactions. The 5',8-cyclization is found
      to be exothermic by approximately 20 kcal/mol but kinetically unfavorable; the
      lowest cyclization transition state (TS) lies about 7 kcal/mol higher than the
      highest TS for conversion between most of the open isomers. In open isomers, the
      two energetically most important attractive interactions are the hydrogen bonds
      (a) between the 2'-OH group and the N3 adenine center and (b) between the 2'-OH
      and 3'-OH groups. The relative ribose-adenine rotation about the C1'-N9 glycosyl
      bond in a certain range changes the energy by as much as 10-15 kcal/mol, the
      origin being (i) the repulsive 2'-H.H-C8 and O1'.N3 and (ii) the attractive 2'
      OH.N3 ribose-adenine interactions. The hypothetical synergy between the glycosyl
      rotation and the Co-C bond scission may contribute to the experimentally
      established labilization of the Co-C bond in enzyme-bound adenosylcobalamin. The
      computational results are not inconsistent with the rotation about the C1'-N9
      glycosyl bond being the principal coordinate for long-range radical migration in
      coenzyme B(12)-dependent enzymes. The effect of the protein environment on the
      model system results reported here remains an open question.

PMID- 12517174
TI  - Dip-pen nanolithography in tapping mode.
AB  - Dip-pen nanolithography (DPN) is becoming a popular nano-patterning technique for
      depositing materials onto a substrate using the probe of an atomic force
      microscope (AFM). Here, we demonstrate the deposition of a short synthetic
      peptide by DPN using the Tapping Mode of AFM rather than the commonly used
      contact mode. DPN in Tapping Mode requires drive amplitude modifications for
      deposition, yet allows for gentle imaging of the deposited material and enables
      deposition on soft surfaces.

PMID- 12517175
TI  - Bound state potential energy surface construction: ab initio zero-point energies
      and vibrationally averaged rotational constants.
AB  - Collins' method of interpolating a potential energy surface (PES) from quantum
      chemical calculations for reactive systems (Jordan, M. J. T.; Thompson, K. C.;
      Collins, M. A. J. Chem. Phys. 1995, 102, 5647. Thompson, K. C.; Jordan, M. J. T.;
      Collins, M. A. J. Chem. Phys. 1998, 108, 8302. Bettens, R. P. A.; Collins, M. A.
      J. Chem. Phys. 1999, 111, 816) has been applied to a bound state problem. The
      interpolation method has been combined for the first time with quantum diffusion
      Monte Carlo calculations to obtain an accurate ground state zero-point energy,
      the vibrationally average rotational constants, and the vibrationally averaged
      internal coordinates. In particular, the system studied was fluoromethane using a
      composite method approximating the QCISD(T)/6-311++G(2df,2p) level of theory. The
      approach adopted in this work (a) is fully automated, (b) is fully ab initio, (c)
      includes all nine nuclear degrees of freedom, (d) requires no assumption of the
      functional form of the PES, (e) possesses the full symmetry of the system, (f)
      does not involve fitting any parameters of any kind, and (g) is generally
      applicable to any system amenable to quantum chemical calculations and Collins'
      interpolation method. The calculated zero-point energy agrees to within 0.2% of
      its current best estimate. A0 and B0 are within 0.9 and 0.3%, respectively, of
      experiment.

PMID- 12517176
TI  - Toward a glucose biosensor based on surface-enhanced Raman scattering.
AB  - This work presents the first step toward a glucose biosensor using surface
      enhanced Raman spectroscopy (SERS). Historically, glucose has been extremely
      difficult to detect by SERS because it has a small normal Raman cross section and
      adsorbs weakly or not at all to bare silver surfaces. In this paper, we report
      the first systematic study of the direct detection of glucose using SERS. Glucose
      is partitioned into an alkanethiol monolayer adsorbed on a silver film over
      nanosphere (AgFON) surface and thereby, it is preconcentrated within the 0-4 nm
      thick zone of electromagnetic field enhancement. The experiments presented herein
      utilize leave-one-out partial least-squares (LOO-PLS) analysis to demonstrate
      quantitative glucose detection both over a large (0-250 mM) and clinically
      relevant (0-25 mM) concentration range. The root-mean-squared error of prediction
      (RMSEP) of 1.8 mM (33.1 mg/dL) in the clinical study is near that desired for
      medical applications (1 mM, 18 mg/dL). Future studies will advance toward true in
      vivo, real time, minimally invasive sensing.

PMID- 12517177
TI  - Macrocyclic glycoclusters. Self-aggregation and phosphate-induced agglutination
      behaviors of calix[4]resorcarene-based quadruple-chain amphiphiles with a huge
      oligosaccharide pool.
AB  - Macrocyclic glycocluster compounds 2n (n = 2-7) with four alkyl (undecyl) chains
      and eight oligosaccharide moieties on the opposite sides of the
      calix[4]resorcarene macrocycle are prepared from the reactions of the
      corresponding octaamine derivative with maltooligosaccharide lactones. Combined
      evidence from dynamic light scattering (DLS), gel permeation chromatography
      (GPC), and transmission electron microscopy (TEM) indicates that they form small
      micelle-like nanoparticles (d congruent with 3 nm) in water. In the presence of
      Na2HPO4/NaH2PO4, nanoparticles are agglutinated with phosphate ions as a glue to
      grow in size up to 60-100 nm, as revealed by DLS as well as microscopy (TEM and
      AFM). The phosphate-induced agglutination processes can be followed by surface
      plasmon resonance (SPR). Amphiphile 2n is readily immobilized on the
      hydrophobized sensor chip of SPR to give a closely packed monolayer with
      oligosaccharide moieties exposed to bulk water. While there is no further
      adsorption of 2n on the resulting monolayer, this does occur when the latter is
      pretreated with the phosphate salts, ultimately giving rise to a multilayer upon
      repeated treatment of the chip with 2n and Na2HPO4/NaH2PO4 in an alternate
      manner. Kinetic analyses show that the phosphate-mediated inter(saccharide)
      interactions in terms of rate and affinity are markedly dependent on the
      oligosaccharide chain lengths (n), becoming more favorable with increasing n's.
      The novel aggregation and agglutination behaviors observed are discussed in terms
      of immobilizable and irreversible micelles on the basis of the cone-shaped
      structure of quadruple-chain amphiphile 2n having a huge saccharide pool and the
      efficiency of multiple hydrogen bonding therein. The unique intermolecular
      binding properties of compound 22 and analogues so far reported are reviewed in
      light of the present finding.

PMID- 12517178
TI  - Organometallic complexes for nonlinear optics. 30.1 electrochromic linear and
      nonlinear optical properties of alkynylbis(diphosphine)ruthenium complexes.
AB  - A combination of cyclic voltammetry, UV-vis-NIR spectroelectrochemistry, time
      dependent density functional theory (TD-DFT), and Z-scan measurements employing a
      modified optically transparent thin-layer electrochemical (OTTLE) cell has been
      used to identify and assign intense transitions of metal alkynyl complexes at
      technologically important wavelengths in the oxidized state and to utilize these
      transitions to demonstrate a facile electrochromic switching of optical
      nonlinearity. Cyclic voltammetric data for the ruthenium(II) complexes trans
      [RuXY(dppe)(2)] [dppe = 1,2-bis(diphenylphosphino)ethane, X = Cl, Y = Cl (1),
      Ctbd1;CPh (2), 4-Ctbd1;CC(6)H(4)Ctbd1;CPh (3); X = Ctbd1;CPh, Y = Ctbd1;CPh (4),
      4-Ctbd1;CC(6)H(4)Ctbd1;CPh (5)] show a quasi-reversible oxidation at 0.50-0.60 V
      (with respect to ferrocene/ferrocenium 0.56 V), which is assigned to the
      Ru(II/III) couple. The ruthenium(III) complex cations trans-[RuXY(dppe)(2)](+)
      were obtained by the in situ oxidation of complexes 1-5 using an OTTLE cell. The
      UV-vis-NIR optical spectra of 1(+)-5(+) contain a low-energy band in the near-IR
      region ( approximately 8000-16 000 cm(-)(1)), in contrast to 1-5, which are
      optically transparent at wavelengths < 22 000 cm(-)(1). TD-DFT calculations have
      been applied to model systems trans-[RuXY(PH(3))(4)] [X = Cl, Y = Cl, Ctbd1;CPh,
      or 4-Ctbd1;CC(6)H(4)Ctbd1;CPh; X = Ctbd1;CPh, Y = Ctbd1;CPh or 4
      Ctbd1;CC(6)H(4)Ctbd1;CPh] to rationalize the optical spectra of 1-5 and 1(+)
      5(+). The important low-energy bands in the electronic spectra of 1(+)-5(+) are
      assigned to the promotion of an electron from either a chloride p orbital or an
      ethynyl p orbital to the partially occupied HOMO. These absorption bands have
      been utilized to demonstrate a facile switching of cubic nonlinear optical (NLO)
      properties at 12 500 cm(-)(1) (corresponding to the wavelength of maximum
      transmission in biological materials such as tissue) using the OTTLE cell, the
      first electrochromic switching of molecular nonlinear refraction and absorption,
      and the first switching of optical nonlinearity using an electrochemical cell.

PMID- 12517179
TI  - Biomethylation of selenium and tellurium: microorganisms and plants.

PMID- 12517180
TI  - Transposition of allylic alcohols into carbonyl compounds mediated by transition
      metal complexes.

PMID- 12517181
TI  - Membrane fusion.

PMID- 12517182
TI  - Nucleophilic substitution reactions by electron transfer.

PMID- 12517183
TI  - Rhodium-catalyzed carbon-carbon bond forming reactions of organometallic
      compounds.

PMID- 12517184
TI  - Thioamides as useful synthons in the synthesis of heterocycles.

PMID- 12517185
TI  - 1,2-Dications in organic main group systems.

PMID- 12517186
TI  - Advances in non-metallocene olefin polymerization catalysis.

PMID- 12517189
TI  - Mirror, mirror on the wall: are we prescribing the right psychotropic medications
      to the right children using the right treatment plan?

PMID- 12517190
TI  - Psychotropic practice patterns for youth: a 10-year perspective.
AB  - OBJECTIVE: To examine changes in the full spectrum of psychotropic medication
      treatment for youths from 1987 to 1996. METHODS: A population-based analysis of
      community treatment data on nearly 900,000 youths enrolled in 2 US health care
      systems included (1) computerized Medicaid data from 2 states (a midwestern state
      and a mid-Atlantic state) composed of outpatient prescription claims and
      enrollment records and (2) computerized prescription dispensing records from a
      group-model health maintenance organization. Ten 1-year cross-sectional data sets
      from 1987 through 1996 were analyzed. RESULTS: Total psychotropic medication
      prevalence for youths increased 2- to 3-fold and included most classes of
      medication. The rapid growth since 1991 of alpha-agonists, neuroleptics, and
      "mood stabilizer" anticonvulsants was particularly notable. The 1996 prevalence
      of any psychotropic medication among youths younger than 20 years was remarkably
      similar (5.9%-6.3%) across all 3 sites, with stimulants and antidepressants
      consistently ranked first and second. Medicaid rates almost always exceeded
      health maintenance organization rates by large margins, particularly for alpha
      agonists, neuroleptics, "mood stabilizer" anticonvulsants, and lithium. Youths in
      health maintenance organizations had rates similar to Medicaid-insured youths for
      antidepressants and hypnotics. Over the decade, there was a proportional increase
      in females receiving stimulants and in males receiving antidepressants,
      particularly for the 10- to 14-year-old group. The prevalence ratios of whites to
      African Americans narrowed substantially in 1 Medicaid site. CONCLUSIONS: Youth
      psychotropic treatment utilization during the 1990s nearly reached adult
      utilization rates. Youth findings can be used to accurately assess the duration
      of treatment and unforeseen practice pattern changes, and to identify safety
      concerns.

PMID- 12517191
TI  - Intrauterine exposure to infection and risk of cerebral palsy in very preterm
      infants.
AB  - OBJECTIVE: To evaluate exposure to intrauterine infection as an independent risk
      factor for spastic cerebral palsy (CP) among very prematurely born infants. STUDY
      DESIGN: Retrospective case-control study. METHODS: Singleton children with
      gestational ages less than 32 weeks and birth weights less than 1999 g who
      survived to age 2 years and were born from 1988 to 1994 in a level 2 or 3
      hospital in California were included in the study. Cases were children with
      congenital spastic CP (n = 170). Controls were children randomly sampled within
      250-g birth weight intervals (n = 270). Gestational age was controlled through
      multiple logistic models. Major analyses were controlled for preeclampsia and
      short time between admission and delivery. RESULTS: Neither clinical nor
      histologic indicators of intrauterine infection were associated with total
      spastic CP or spastic diplegia in these infants. Although not predicted by prior
      hypothesis, we observed an approximate doubling of risk for infants of infected
      mothers among children born to white women, whereas no association was noted
      among children born to women of other races/ethnicities. White controls had lower
      frequency of all measured infection indicators compared with white cases and
      cases and controls of other races/ethnicities. CONCLUSION: Exposure to
      intrauterine infection was not an independent risk factor for CP in very
      premature infants when gestational age and other confounders were tightly
      controlled.

PMID- 12517192
TI  - Infant-parent bed sharing in an inner-city population.
AB  - BACKGROUND: In the United States, infant-parent bed sharing is a controversial
      and poorly understood practice. Proponents site potential advantages such as
      increases in bonding and facilitation of breastfeeding, whereas opponents site
      potential increases in risks of suffocation and sudden infant death syndrome,
      particularly among mothers who smoke. Few studies have examined normative
      practices in low-income populations. OBJECTIVES: To describe sleep practices in a
      cohort of infants born to predominantly low-income, inner-city mothers, to
      examine stability in sleep practices during the first 7 to 12 months of life, and
      to identify factors associated with bed sharing. DESIGN AND SETTING: Prospective
      birth cohort study in the District of Columbia, with recruitment taking place
      between August 1995 and September 1996 and follow-up from November 1995 to
      September 1997. PARTICIPANTS: Maternal-infant pairs were systematically selected
      from 3 hospitals. We interviewed 394 mothers shortly after delivery and at 3 to 7
      months post partum. Of these, 369 were interviewed again at 7 to 12 months post
      partum. MAIN OUTCOME MEASURE: Usual bed sharing. RESULTS: At age 3 to 7 months
      (mean age, 129 days), 201 infants (51%) usually slept alone and 191 (48%) usually
      slept in a bed with a parent or other adult. Similarly, at age 7 to 12 months
      (mean age, 262 days), 190 infants (51%) usually slept alone and 175 (47%) usually
      slept in a bed with a parent or other adult. Of the infants who slept with a
      parent or other adult at age 3 to 7 months, 75% continued to do so at age 7 to 12
      months. Similarly, of infants who usually slept alone at age 3 to 7 months, only
      22% were reported to be usual bed sharers at age 7 to 12 months. In multivariate
      analyses, factors associated with bed sharing at both follow-up interviews
      included single marital status of the mother (first interview: odds ratio [OR] =
      1.90; 95% confidence interval [CI], 1.11-3.27; second interview: OR = 1.81; 95%
      CI, 1.02-3.25) and 1 or more moves since the birth of the infant (first
      interview: OR = 1.82; 95% CI, 1.10-3.01; second interview: OR = 1.73; 95% CI,
      1.05-2.86). Breastfeeding and household crowding were not significantly
      associated with bed sharing. CONCLUSIONS: Bed sharing was common in this inner
      city population, and sleep practices were relatively stable during the first 7 to
      12 months of life. These findings underscore the need for additional research
      clarifying the benefits and risks of bed sharing.

PMID- 12517193
TI  - Trends in infant bed sharing in the United States, 1993-2000: the National Infant
      Sleep Position study.
AB  - BACKGROUND: Bed sharing with parents has been described as both beneficial to
      infant well-being and as a potentially lethal situation. OBJECTIVE: To examine
      trends in bed sharing between infants and caregivers, and the factors that
      influence this behavior. DESIGN: Annual nationally representative telephone
      surveys conducted between 1993 and 2000. SETTING: The 48 contiguous United
      States. PARTICIPANTS: Nighttime caregivers of infants born within 7 months prior
      to interview between 1993 and 2000. Approximately 1000 interviews were conducted
      each year for a total sample of 8453 nighttime caregivers. MAIN OUTCOME MEASURES:
      Where and with whom the infant usually slept at night in the preceding 2 weeks.
      RESULTS: Forty-five percent of infants spent at least some time at night on an
      adult bed in the last 2 weeks. Between 1993 and 2000, the proportion of infants
      usually sharing an adult bed at night increased from 5.5% to 12.8%. More than 90%
      of infants who "usually" slept on an adult bed shared it with their parents. In a
      multivariate analysis, factors associated with increased probability of routine
      bed sharing included: maternal age less than 18 years (odds ratio [OR] = 2.26;
      95% confidence interval [CI], 1.22-4.21), maternal race or ethnicity reported as
      black (OR = 4.04; 95% CI, 3.04-5.36) or as Asian or "other" (OR = 2.72; 95% CI,
      1.74-4.22), household income less than $20,000 (OR = 1.49; 95% CI, 1.15 = 1.92),
      living in the Southern states compared with living in the Midwest (OR, 1.59; 95%
      CI = 1.23, 2.06), and infant age less than 8 weeks (OR = 1.60; 95% CI, 1.10
      2.33). Living in the Mid-Atlantic compared with the Midwest (OR = 0.63; 95% CI,
      0.44-0.90), and being born with low birthweight and preterm (OR = 0.32; 95% CI,
      0.14-0.74) were associated with decreased probability of routine bed sharing.
      CONCLUSIONS: Bed sharing as a routine practice is growing in the United States.
      Given that this practice seems to be widespread and strongly influenced by
      cultural factors, more studies of the consequences of bed sharing are needed to
      inform health care providers and parents on the risks and benefits.

PMID- 12517194
TI  - Prevalence of traumatic injuries in drowning and near drowning in children and
      adolescents.
AB  - OBJECTIVE: To determine the prevalence of traumatic injuries in children involved
      in drowning and near-drowning accidents. DESIGN/METHODS: Ten-year retrospective
      medical chart review of patients at an urban tertiary care pediatric facility.
      Included patients had International Classification of Diseases, Ninth Revision,
      Clinical Modification codes for fatal/nonfatal drowning or E codes for fall into
      water, accidental drowning, and submersion. We recorded demographics, event
      characteristics, diagnostics, and outcome data. We used the chi(2) or the Fisher
      exact test to compare patients with and without injuries. RESULTS: One hundred
      forty-three patients met inclusion criteria. Of these, 95 (66.4%) were male.
      Median age was 3.8 years, and 30 (23.4%) of 128 had preexisting conditions. Site
      of drowning was the pool (70.6%), the bathtub (19.0%), or natural water (10.4%).
      The prevalence of traumatic injury was 4.9% (95% confidence interval, 0%-28%).
      The predominant mechanism of injury was diving, and all injuries were to the
      cervical spine. Patients with injury were more likely to be older (mean age, 13.5
      vs 5.1 years; P<.001) and to have a history of diving (85.7% vs 2.2%; P<.001).
      The presence of injury was not associated with sex, preexisting condition, or
      site of drowning (P>.05). CONCLUSIONS: The prevalence of traumatic injury in
      drowning and near drowning is low. We identified only cervical spine injuries,
      and all but 1 patient had a clear history of diving. Use of specialized trauma
      evaluations may not be warranted for patients in drowning and near-drowning
      accidents without a clear history of traumatic mechanism.

PMID- 12517195
TI  - Association between antibiotic use and primary idiopathic intussusception.
AB  - BACKGROUND: Intussusception is the leading cause of intestinal obstruction in
      young children. Antibiotics are the most frequently prescribed medication in the
      pediatric population and have common adverse effects on the gastrointestinal
      tract. OBJECTIVE: To determine whether a relationship exists between primary
      idiopathic intussusception and antibiotic drug use. DESIGN: Case-control study.
      PARTICIPANTS: Ninety-three case patients with intussusception and 353 injury
      controls younger than 4 years who were seen at the emergency department of the
      Children's Hospital of Alabama between January 1, 1996, and April 30, 2001, were
      included. Controls were matched to cases by quarter and year of time of
      diagnosis, age, and sex. MAIN OUTCOME MEASURES: Odds ratios and 2-sided 95%
      confidence intervals were estimated using conditional logistic regression.
      Prevalence of antibiotic use in an age-standardized, representative sample of US
      children from NHANES III (Third National Health and Nutrition Examination Survey)
      was used for external comparisons. RESULTS: Antibiotic use within 48 hours of
      diagnosis was found in 23 cases (25%) and 33 controls (9%) (odds ratio, 4.15; 95%
      confidence interval, 2.17-7.92; attributable risk, 18.7%). Antibiotic use among
      US children according to NHANES III was 10.7%. In cases, the beta-lactam class
      accounted for 78% of all medications used. Cephalosporin use was associated with
      more than a 20-fold increased risk of intussusception. CONCLUSION: An association
      between antibiotic drug use and intussusception was identified.

PMID- 12517196
TI  - Incidence and impact of adverse drug events in pediatric inpatients.
AB  - OBJECTIVES: To determine the incidence and causes of adverse drug events (ADEs)
      and potential ADEs in hospitalized children, and to examine the consequences of
      these events. DESIGN: Prospective review of medical records and staff interviews
      were performed. The ADEs were defined as injuries from medications or lack of an
      intended medication, and potential ADEs, as errors with the potential to result
      in injury. SETTING: A general pediatric unit and a pediatric intensive care unit
      in a metropolitan medical center. PATIENTS: A total of 1197 consecutive patient
      admissions were studied from September 15, 2000, to May 10, 2001. The admissions
      represented a total of 922 patients and 10,164 patient-days. RESULTS: The ADEs
      (6/100 admissions, 7.5/1000 patient-days) and potential ADEs (8/100 admissions,
      9.3/1000 patient-days) were common in hospitalized children. Demographic
      variables associated with the occurrence of these events were the length of
      hospital stay, case-mix index, and amount of medication exposure. After adjusting
      for length of stay, medication exposure continued to have a significant influence
      on ADEs and potential ADEs. For ADEs, 18 (24%) were judged to be serious or life
      threatening. Most ADEs were not associated with major or permanent disability.
      Patients with both ADEs and potential ADEs were less likely to be routinely
      discharged and more likely to be discharged with home health care or to another
      institution, suggesting that patient disposition was not related to the adverse
      event. CONCLUSIONS: Both ADEs and potential ADEs are common among hospitalized
      children with greater disease burden and medication exposure. These findings
      suggest that these events were a consequence, rather than a cause, of more severe
      illness.

PMID- 12517197
TI  - The effect of maternal milk on neonatal morbidity of very low-birth-weight
      infants.
AB  - OBJECTIVE: To examine the dose effect of maternal milk on neonatal morbidity of
      very low-birth-weight (<1.5 kg) infants. DESIGN: Prospective observational study.
      SETTING: An urban tertiary care neonatal intensive care unit and follow-up
      clinic. POPULATION: One hundred nineteen singleton very low-birth-weight infants
      admitted from January 1, 1997, to February 14, 1999 (mean birth weight, 1056 g;
      mean gestational age, 28 weeks; 57% male; and 43% white). METHODS: A comparison
      of the effect on neonatal outcomes of daily graded doses (1-24, 25-49, and > or =
      50 mL/kg of body weight) of maternal milk through week 4 of life vs a reference
      group receiving no maternal milk. MAIN OUTCOME MEASURES: Neonatal outcomes
      examined included rates of sepsis after age 5 days, retinopathy of prematurity,
      chronic lung disease, necrotizing enterocolitis, jaundice, duration of ventilator
      dependence, and length of hospital stay. RESULTS: Seventy-nine infants (66%)
      received maternal milk, of whom 32 received at least 50 mL/kg per day through
      week 4 of life. Poisson regression analysis adjusting for birth weight, sex, and
      ethnicity revealed that the mean number of episodes of sepsis for infants
      receiving at least 50 mL/kg per day was lower by a factor of 0.27 (95% confidence
      interval, 0.08-0.95) compared with infants receiving no maternal milk. There was
      no effect of maternal milk on other neonatal outcomes. CONCLUSIONS: A daily
      threshold amount of at least 50 mL/kg of maternal milk through week 4 of life is
      needed to decrease the rate of sepsis in very low-birth-weight infants, but
      maternal milk does not affect other neonatal morbidities.

PMID- 12517198
TI  - A pilot study of milk odor effect on nonnutritive sucking by premature newborns.
AB  - OBJECTIVE: To study the effect of milk odor on nonnutritive sucking by premature
      newborns. DESIGN: Blinded, crossover study of the effects of milk vs sham odor on
      nonnutritive sucking. SETTING: Urban neonatal intensive care unit. PATIENTS:
      Twenty-nine premature newborns with gestational age of 29 to 36 weeks.
      INTERVENTION: Fourteen subjects were tested with fortified breast milk odor
      (group 1) and 15 were tested with formula odor (group 2). For the test
      observation, milk odor was directed to the nose (orthonasal exposure) using a
      specially modified pacifier. For the control observation, water was used as a
      sham odor. Observations were made concurrently with tube feeding of the newborn
      with either fortified breast milk (group 1) or formula (group 2). MAIN OUTCOME
      MEASURES: Total number of sucks and sucking bursts, measured from a digital
      record of pressure changes within the pacifier. RESULTS: Nutrient odor increased
      suck bursts in group 1 subjects, with borderline statistical significance (46.6
      bursts/10 min with odor [95% confidence interval (CI), 39-54] vs 35.4 bursts/10
      min without odor [95% CI, 28-43]). Unexpectedly, when test and control
      observations were combined, subjects in group 1 showed an overall increase in
      number of sucks (260.4 [95% CI, 206-315]) and suck bursts (41.0 [95% CI, 36-46])
      compared with group 2 subjects (144.8 [95% CI, 87-203] vs 27.4 [95% CI, 21-34]).
      CONCLUSIONS: Nutrient odor exposure via pacifier may stimulate nonnutritive
      sucking during gavage feeding of premature newborns. Further studies on the
      effects of nutrient odor on nonnutritive sucking by premature newborns must take
      into account the effects of nutrients given via gavage.

PMID- 12517199
TI  - Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to
      treat wheezing in children aged 2 to 24 months in a pediatric emergency
      department.
AB  - OBJECTIVE: To determine if administration of albuterol by a metered-dose inhaler
      with a spacer device is as efficacious as administration of albuterol by
      nebulizer to treat wheezing in children aged 2 years and younger. DESIGN: Double
      blind, randomized, placebo-controlled clinical trial. SETTING: Pediatric
      emergency department. PATIENTS: From a convenience sample of wheezing children
      aged 2 to 24 months, 85 patients were enrolled in the nebulizer group and 83 in
      the spacer group. INTERVENTIONS: The nebulizer group received a placebo metered
      dose inhaler with a spacer followed by nebulized albuterol. The spacer group
      received albuterol by a metered-dose inhaler with a spacer followed by nebulized
      isotonic sodium chloride solution. Treatments were given every 20 minutes by a
      single investigator blinded to group assignment. MAIN OUTCOME MEASURES: The
      primary outcome was admission rate. Pulmonary Index score and oxygen saturation
      were measured initially and 10 minutes after each treatment. RESULTS: The
      nebulizer group had a significantly higher mean (SD) initial Pulmonary Index
      score compared with the spacer group (7.6 [2.5] vs 6.6 [2.0]; P =.002). With the
      initial Pulmonary Index score controlled, children in the spacer group were
      admitted less (5% vs 20%; P =.05). Analyses also revealed an interaction between
      group and initial Pulmonary Index score; lower admission rates in the spacer
      group were found primarily in children having a more severe asthma exacerbation.
      CONCLUSION: Our data suggest that metered-dose inhalers with spacers may be as
      efficacious as nebulizers for the emergency department treatment of wheezing in
      children aged 2 years or younger.

PMID- 12517200
TI  - Asthma medication use and disease burden in children in a primary care
      population.
AB  - BACKGROUND: Children with persistent asthma underuse controller medications and
      overuse relievers. A better understanding of the appropriateness of regimens,
      medication adherence, and adequacy of asthma control is needed. OBJECTIVES: To
      describe use of asthma medications and disease burden in children with persistent
      asthma, to determine whether use of controllers and relievers is consistent with
      national guidelines, and to estimate adequacy of asthma control. DESIGN: Cross
      sectional cohort study. SETTING: Forty-two primary care practices participating
      in 3 regions of the United States. PARTICIPANTS: Parents of 638 children aged 3
      to 15 years with asthma. MAIN OUTCOMES MEASURES: Asthma symptom-days, use of
      reliever and controller medications, and adequacy of asthma control, ascertained
      by face-to-face questionnaire. RESULTS: The mean age was 9.4 years, and 59.9%
      were boys. In the preceding 2 weeks, two thirds (67.5%) of subjects had 0 to 4
      symptom-days, 15.8% had 5 to 9 symptom-days, and 16.6% had 10 to 14 symptom-days
      (percentages do not total 100 because of rounding). One third (32.6%) of children
      using relievers had high levels of use. One third (34.3%) of children using
      controllers used them 4 or fewer days per week. Among children with some evidence
      of persistent disease (use of controllers, excess symptoms, or excess reliever
      use), almost two thirds (64.3%) were inadequately controlled. This group
      consisted both of children reportedly using controllers less than recommended and
      those reporting not receiving controller medication at all. CONCLUSIONS: In this
      insured population, inappropriate reliance on relievers and nonadherence to
      controllers were common. Inadequate asthma control was common regardless of
      whether controllers were prescribed.

PMID- 12517201
TI  - Minimizing risks: the ethics of predictive diabetes mellitus screening research
      in newborns.
AB  - Type 1 diabetes mellitus is the most common metabolic disease of childhood. Two
      states offer newborn screening to identify children with a genetic predisposition
      to it. It is a voluntary test offered in conjunction with the mandatory newborn
      metabolic screening. There are no preventive treatments, but children discovered
      to be at increased risk may participate in follow-up studies to determine whether
      and when the child develops autoantibodies (preclinical disease) or overt
      diabetes. This study examined the ethics of predictive genetic research in
      newborns for type 1 diabetes. Prediction research has serious psychosocial
      implications, and research designs must account for them. The study concluded
      that, to minimize harm to infants and their families, (1) if the research does
      not incorporate a prevention strategy, studies should avoid disclosure of
      results; and (2) if disclosure is necessary, then the research should be
      restricted to newborns with an affected first-degree relative.

PMID- 12517202
TI  - Demographic, intrinsic, and extrinsic factors associated with weapon carrying at
      school.
AB  - BACKGROUND: Recent incidents of school violence have heightened the need to
      identify societal, interpersonal, and adolescent characteristics that contribute
      to weapon carrying. OBJECTIVES: To assess the prevalence of weapon carrying at
      school and to determine associated risk factors for adolescent males and females.
      DESIGN: A cross-sectional study using the 1994-1995 National Longitudinal Study
      of Adolescent Health data. PARTICIPANTS: A nationally representative sample of
      6504 adolescents and their parents. MAIN OUTCOME MEASURE: Whether adolescents
      have ever carried a weapon at school. STATISTICS: chi(2) Analyses and
      hierarchical regressions were done using SPSS (SPSS Inc, Chicago, Ill) and SUDAAN
      (Research Triangle Park, NC) software. Regression models included demographic,
      intrinsic, and extrinsic factors. RESULTS: Of the overall sample, 9.3% (n = 595)
      reported having carried a weapon at school. Of these, 77% were male (male vs
      female adjusted odds ratio [AOR], 3.1; 95% confidence interval [CI], 2.3-4.1).
      Substance use, school problems, perpetration of violence, and witnessing violence
      were significantly associated with weapon carrying for both males and females.
      However, for males, extrinsic factors were more important in mediating the
      effects of substance use and perpetration of physical violence on school weapon
      carrying, while intrinsic factors mediate these variables for females.
      CONCLUSION: These findings suggest that interventions for violence prevention for
      males and females need to be targeted toward different areas.

PMID- 12517203
TI  - Inadequate recognition of education resources required for high-risk students
      with sickle cell disease.

PMID- 12517205
TI  - A piece of my mind. Family history.

PMID- 12517206
TI  - Gene chips inch toward the clinic.

PMID- 12517207
TI  - John Quackenbush talks about the clinical promise of genetic microarrays.
      Interviewed by Brian Vastag.

PMID- 12517208
TI  - Teenage smoking continues to decrease.

PMID- 12517212
TI  - JAMA patient page. Pressure ulcers.

PMID- 12517214
TI  - Shock wave therapy for treatment of plantar fasciitis.

PMID- 12517215
TI  - Shock wave therapy for treatment of plantar fasciitis.

PMID- 12517216
TI  - Shock wave therapy for treatment of plantar fasciitis.

PMID- 12517217
TI  - Vitamin supplementation in elderly persons.

PMID- 12517218
TI  - Vitamin supplementation in elderly persons.

PMID- 12517220
TI  - Pulse pressure and risk of cardiovascular disease.

PMID- 12517222
TI  - Pulse pressure and risk of cardiovascular disease.

PMID- 12517223
TI  - Continuous nursing support during labor.

PMID- 12517225
TI  - Research in medical education.

PMID- 12517227
TI  - El Nino and incidence of hemorrhagic fever with renal syndrome in China.

PMID- 12517228
TI  - Mortality associated with influenza and respiratory syncytial virus in the United
      States.
AB  - CONTEXT: Influenza and respiratory syncytial virus (RSV) cause substantial
      morbidity and mortality. Statistical methods used to estimate deaths in the
      United States attributable to influenza have not accounted for RSV circulation.
      OBJECTIVE: To develop a statistical model using national mortality and viral
      surveillance data to estimate annual influenza- and RSV-associated deaths in the
      United States, by age group, virus, and influenza type and subtype. DESIGN,
      SETTING, AND POPULATION: Age-specific Poisson regression models using national
      viral surveillance data for the 1976-1977 through 1998-1999 seasons were used to
      estimate influenza-associated deaths. Influenza- and RSV-associated deaths were
      simultaneously estimated for the 1990-1991 through 1998-1999 seasons. MAIN
      OUTCOME MEASURES: Attributable deaths for 3 categories: underlying pneumonia and
      influenza, underlying respiratory and circulatory, and all causes. RESULTS:
      Annual estimates of influenza-associated deaths increased significantly between
      the 1976-1977 and 1998-1999 seasons for all 3 death categories (P<.001 for each
      category). For the 1990-1991 through 1998-1999 seasons, the greatest mean numbers
      of deaths were associated with influenza A(H3N2) viruses, followed by RSV,
      influenza B, and influenza A(H1N1). Influenza viruses and RSV, respectively, were
      associated with annual means (SD) of 8097 (3084) and 2707 (196) underlying
      pneumonia and influenza deaths, 36 155 (11 055) and 11 321 (668) underlying
      respiratory and circulatory deaths, and 51 203 (15 081) and 17 358 (1086) all
      cause deaths. For underlying respiratory and circulatory deaths, 90% of influenza
      and 78% of RSV-associated deaths occurred among persons aged 65 years or older.
      Influenza was associated with more deaths than RSV in all age groups except for
      children younger than 1 year. On average, influenza was associated with 3 times
      as many deaths as RSV. CONCLUSIONS: Mortality associated with both influenza and
      RSV circulation disproportionately affects elderly persons. Influenza deaths have
      increased substantially in the last 2 decades, in part because of aging of the
      population, underscoring the need for better prevention measures, including more
      effective vaccines and vaccination programs for elderly persons.

PMID- 12517229
TI  - Years of life lost due to obesity.
AB  - CONTEXT: Public health officials and organizations have disseminated health
      messages regarding the dangers of obesity, but these have not produced the
      desired effect. OBJECTIVE: To estimate the expected number of years of life lost
      (YLL) due to overweight and obesity across the life span of an adult. DESIGN,
      SETTING, AND SUBJECTS: Data from the (1) US Life Tables (1999); (2) Third
      National Health and Nutrition Examination Survey (NHANES III; 1988-1994); and (3)
      First National Health and Nutrition Epidemiologic Follow-up Study (NHANES I and
      II; 1971-1992) and NHANES II Mortality Study (1976-1992) were used to derive YLL
      estimates for adults aged 18 to 85 years. Body mass index (BMI) integer-defined
      categories were used (ie, <17; 17 to <18; 18 to <19; 20 to <21; 21 to 45; or > or
      =45). A BMI of 24 was used as the reference category. MAIN OUTCOME MEASURE: The
      difference between the number of years of life expected if an individual were
      obese vs not obese, which was designated YLL. RESULTS: Marked race and sex
      differences were observed in estimated YLL. Among whites, a J- or U-shaped
      association was found between overweight or obesity and YLL. The optimal BMI
      (associated with the least YLL or greatest longevity) is approximately 23 to 25
      for whites and 23 to 30 for blacks. For any given degree of overweight, younger
      adults generally had greater YLL than did older adults. The maximum YLL for white
      men aged 20 to 30 years with a severe level of obesity (BMI >45) is 13 and is 8
      for white women. For men, this could represent a 22% reduction in expected
      remaining life span. Among black men and black women older than 60 years,
      overweight and moderate obesity were generally not associated with an increased
      YLL and only severe obesity resulted in YLL. However, blacks at younger ages with
      severe levels of obesity had a maximum YLL of 20 for men and 5 for women.
      CONCLUSION: Obesity appears to lessen life expectancy markedly, especially among
      younger adults.

PMID- 12517230
TI  - Burden of systolic and diastolic ventricular dysfunction in the community:
      appreciating the scope of the heart failure epidemic.
AB  - CONTEXT: Approximately half of patients with overt congestive heart failure (CHF)
      have diastolic dysfunction without reduced ejection fraction (EF). Yet, the
      prevalence of diastolic dysfunction and its relation to systolic dysfunction and
      CHF in the community remain undefined. OBJECTIVES: To determine the prevalence of
      CHF and preclinical diastolic dysfunction and systolic dysfunction in the
      community and determine if diastolic dysfunction is predictive of all-cause
      mortality. DESIGN, SETTING, PARTICIPANTS: Cross-sectional survey of 2042 randomly
      selected residents of Olmsted County, Minnesota, aged 45 years or older from June
      1997 through September 2000. MAIN OUTCOME MEASURES: Doppler echocardiographic
      assessment of systolic and diastolic function. Presence of CHF diagnosis by
      review of medical records with designation as validated CHF if Framingham
      criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or
      systolic dysfunction were considered as having either preclinical diastolic or
      preclinical systolic dysfunction. RESULTS: The prevalence of validated CHF was
      2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than
      50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic
      dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and
      0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%
      6.7%) of the population having moderate or severe diastolic dysfunction with
      normal EF. The prevalence of any systolic dysfunction (EF < or =50%) was 6.0%
      (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF < or =40%)
      being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those
      with systolic or diastolic dysfunction than in those with normal ventricular
      function. However, even among those with moderate or severe diastolic or systolic
      dysfunction, less than half had recognized CHF. In multivariate analysis,
      controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31
      [95% CI, 3.00-23.1], P<.001) and moderate or severe diastolic dysfunction (hazard
      ratio, 10.17 [95% CI, 3.28-31.0], P<.001) were predictive of all-cause mortality.
      CONCLUSIONS: In the community, systolic dysfunction is frequently present in
      individuals without recognized CHF. Furthermore, diastolic dysfunction as
      rigorously defined by comprehensive Doppler techniques is common, often not
      accompanied by recognized CHF, and associated with marked increases in all-cause
      mortality.

PMID- 12517231
TI  - Effect of serologic status and cesarean delivery on transmission rates of herpes
      simplex virus from mother to infant.
AB  - CONTEXT: Neonatal herpes most commonly results from fetal exposure to infected
      maternal genital secretions at the time of delivery. The risk of transmission
      from mother to infant as it relates to maternal herpes simplex virus (HSV)
      serologic status and exposure to HSV in the maternal genital tract at the time of
      labor has not been quantified. Furthermore, no data exist on whether cesarean
      delivery, the standard of care for women with genital herpes lesions at the time
      of delivery, reduces HSV transmission. OBJECTIVE: To determine the effects of
      viral shedding, maternal HSV serologic status, and delivery route on the risk of
      transmission of HSV from mother to infant. DESIGN: Prospective cohort of pregnant
      women enrolled between January 1982 and December 1999. SETTINGS: A university
      medical center, a US Army medical center, and 5 community hospitals in Washington
      State. PATIENTS: A total of 58 362 pregnant women, of whom 40 023 had HSV
      cultures obtained from the cervix and external genitalia and 31 663 had serum
      samples tested for HSV. MAIN OUTCOME MEASURE: Rates of neonatal HSV infection.
      RESULTS: Among the 202 women from whom HSV was isolated at the time of labor, 10
      (5%) had neonates with HSV infection (odds ratio [OR], 346; 95% confidence
      interval [CI], 125-956 for neonatal herpes when HSV was isolated vs not
      isolated). Cesarean delivery significantly reduced the HSV transmission rate
      among women from whom HSV was isolated (1 [1.2%] of 85 cesarean vs 9 [7.7%] of
      117 vaginal; OR, 0.14; 95% CI, 0.02-1.08; P =.047). Other risk factors for
      neonatal HSV included first-episode infection (OR, 33.1; 95% CI, 6.5-168), HSV
      isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1 vs HSV-2 isolation
      at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive monitoring (OR, 6.8;
      95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95% CI, 1.2-16), and maternal
      age less than 21 years (OR, 4.1; 95% CI, 1.1-15). Neonatal HSV infection rates
      per 100 000 live births were 54 (95% CI, 19.8-118) among HSV-seronegative women,
      26 (95% CI, 9.3-56) among women who were HSV-1-seropositive only, and 22 (95% CI,
      4.4-64) among all HSV-2-seropositive women. CONCLUSION: Neonatal HSV infection
      rates can be reduced by preventing maternal acquisition of genital HSV-1 and HSV
      2 infection near term. It can also be reduced by cesarean delivery and limiting
      the use of invasive monitors among women shedding HSV at the time of labor.

PMID- 12517232
TI  - Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric
      symptoms and functional impairment in Alzheimer disease: a meta-analysis.
AB  - CONTEXT: Cholinesterase inhibitors are the primary treatment for the cognitive
      symptoms of Alzheimer disease (AD). Cholinergic dysfunction is also associated
      with neuropsychiatric and functional deficits, but results from randomized
      controlled trials of cholinesterase inhibitors are conflicting. OBJECTIVE: To
      conduct a systematic review and meta-analysis to quantify the efficacy of
      cholinesterase inhibitors for neuropsychiatric and functional outcomes in
      patients with mild to moderate AD. DATA SOURCES: We performed a literature search
      of trials using MEDLINE (January 1966-December 2001), Dissertations Abstracts On
      line, PSYCHINFO, BIOSIS, PubMed, and the Cochrane Controlled Trials Register. We
      retrieved English- and non-English-language articles for review and collected
      references from bibliographies of reviews, original research articles, and other
      articles of interest. We searched for both published and unpublished trials,
      contacting researchers and pharmaceutical companies. STUDY SELECTION: We included
      29 parallel-group or crossover randomized, double-blind, placebo-controlled
      trials of outpatients who were diagnosed as having mild to moderate probable AD
      and were treated for at least 1 month with a cholinesterase inhibitor. Sixteen
      trials included neuropsychiatric and 18 included functional measures. DATA
      EXTRACTION: Two investigators (N.H.T. and J.H.) independently extracted study
      methods, sources of bias, and outcomes. Neuropsychiatric outcomes were measured
      with the Neuropsychiatric Inventory (NPI, 0-120 points) and the Alzheimer Disease
      Assessment Scale, noncognitive (ADAS-noncog, 0-50 points) and were analyzed with
      the weighted mean difference method. Functional outcomes were measured with
      several activities of daily living (ADL) and instrumental activities of daily
      living (IADL) scales and analyzed with the standardized mean difference method.
      DATA SYNTHESIS: For neuropsychiatric outcomes, 10 trials included the ADAS-noncog
      and 6 included the NPI. Compared with placebo, patients randomized to
      cholinesterase inhibitors improved 1.72 points on the NPI (95% confidence
      interval [CI], 0.87-2.57 points), and 0.03 points on the ADAS-noncog (95% CI,
      0.00-0.05 points). For functional outcomes, 14 trials used ADL and 13 trials used
      IADL scales. Compared with placebo, patients randomized to cholinesterase
      inhibitors improved 0.1 SDs on ADL scales (95% CI, 0.00-0.19 SDs), and 0.09 SDs
      on IADL scales (95% CI, 0.01 to 0.17 SDs). There was no difference in efficacy
      among various cholinesterase inhibitors. CONCLUSIONS: These results indicate that
      cholinesterase inhibitors have a modest beneficial impact on neuropsychiatric and
      functional outcomes for patients with AD. Future research should focus on how
      such improvements translate into long-term outcomes such as patient quality of
      life, institutionalization, and caregiver burden.

PMID- 12517233
TI  - Artificial and bioartificial support systems for acute and acute-on-chronic liver
      failure: a systematic review.
AB  - CONTEXT: Artificial and bioartificial support systems may provide a "bridge" for
      patients with severe liver disease to recovery or transplantation. OBJECTIVE: To
      evaluate the effect of artificial and bioartificial support systems for acute and
      acute-on-chronic liver failure. DATA SOURCES: Randomized trials on any support
      system vs standard medical therapy were included irrespective of publication
      status or language. Nonrandomized studies were included in explorative analyses.
      Trials were identified through electronic searches (Cochrane Hepato-Biliary Group
      Controlled Trials Register, Cochrane Library, MEDLINE, EMBASE, and the Chinese
      Medical Database), bibliographies, and contact with experts. Searches were
      conducted of the entire databases through September 2002. STUDY SELECTION: Of 528
      references identified, 12 randomized trials with 483 patients were included.
      Eight nonrandomized studies were included in explorative analyses. DATA
      EXTRACTION: Data were extracted and trial quality was assessed independently by 3
      reviewers (L.L.K., J.L., B.A-N.). The primary outcome measure was all-cause
      mortality. Results were combined on the risk ratio (RR) scale. Random-effects
      models were used. Sources of heterogeneity were explored through meta-regression
      and stratified meta-analyses. DATA SYNTHESIS: Of the 12 trials included, 10
      assessed artificial systems for acute or acute-on-chronic liver failure and 2
      assessed bioartificial systems for acute liver failure. Overall, support systems
      had no significant effect on mortality compared with standard medical therapy
      (RR, 0.86; 95% confidence interval [CI], 0.65-1.12). Meta-regression indicated
      that the effect of support systems depended on the type of liver failure (P
      =.03). In stratified meta-analyses, support systems appeared to reduce mortality
      by 33% in acute-on-chronic liver failure (RR, 0.67; 95% CI, 0.51-0.90), but not
      in acute liver failure (RR, 0.95; 95% CI, 0.71-1.29). Compared with randomized
      trials, nonrandomized studies produced significantly larger estimates of
      intervention effects (P =.01). CONCLUSION: This review suggests that artificial
      support systems reduce mortality in acute-on-chronic liver failure compared with
      standard medical therapy. Artificial and bioartificial support systems did not
      appear to affect mortality in acute liver failure.

PMID- 12517234
TI  - Pressure ulcer prevention and management.

PMID- 12517235
TI  - Influenza-related mortality: considerations for practice and public health.

PMID- 12517236
TI  - Obesity in the United States: a fresh look at its high toll.

PMID- 12517239
TI  - Recent progress in ankylosing spondylitis treatment.
AB  - Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease
      responsible for back pain, stiffness and loss of functional capacity. The
      therapeutic management of AS includes regular physical exercise together with the
      use of NSAIDs. Second-line treatments, such as sulfasalazine, are required in
      cases of NSAID-refractory AS. Some patients have severe and inadequately
      controlled disease, explaining the need for the development of new treatments.
      This therapeutic development in AS involves the assessment of new NSAIDs, namely
      COX2 selective agents and new second-line treatments, such as methotrexate (MTX),
      pamidronate and anti-TNFalpha agents. Controlled studies are lacking for MTX.
      Pamidronate showed to be effective in NSAID refractory AS patients in open and
      controlled trials. Anti-TNFalpha agents (infliximab and etanercept) gave
      promising results with dramatic improvement of AS symptoms in open and
      preliminary controlled trials, but further studies are required to evaluate the
      real long-term effects and tolerability of these drugs.

PMID- 12517240
TI  - Paracetamol and asthma.
AB  - Paracetamol (acetaminophen) is one of the over-the-counter analgesics that is
      used frequently for the self-management of some of the common disorders. There
      seems to be two types of relations between paracetamol and asthma - paracetamol
      intolerance leading to bronchospasm in analgesic-induced asthmatics; and the
      relation between asthma and the amount and frequency of consumption of
      paracetamol. Paracetamol is generally recommended as one of the safer analgesics
      in both analgesic tolerant and intolerant asthmatics, without the fear of severe
      bronchospasm that aspirin and other non-steroidal anti-inflammatory drugs can
      induce in these patients. However, Paracetamol is reported to cross-react with
      aspirin at a rate of approximately 20-30% in a dose-dependent way. Therefore, it
      should not be recommended to analgesic intolerant asthmatics, without performing
      oral provocation tests to prove its safety. The possible association between the
      amount and frequency of paracetamol consumption and the prevalence and degree of
      asthma as suggested by some of the recent surveys, needs to be investigated
      further.

PMID- 12517241
TI  - Inhaled corticosteroids plus long-acting beta2-agonists as a combined therapy in
      asthma.
AB  - Inhaled corticosteroids (ICS) are the mainstay of asthma treatment. Since 1994,
      when the first trial showed an equivalent effect of doubling the ICS dose or
      adding salmeterol, it has repeatedly been shown that the combinations of
      beclomethasone dipropionate and salmeterol, budesonide and formoterol, or
      fluticasone propionate and salmeterol have at least the same efficacy as doubling
      the dose of the ICS in adults, though a conclusive trial in asthmatic children is
      still lacking. The addition of a long-acting beta(2)-agonist (LABA) to ICS
      appears more efficacious than adding a short-acting beta(2)-agonist or an
      antileukotriene, even though available data are sparse. Concurrent (two inhalers)
      and combination (same inhaler) modes of administration are equivalent from the
      clinical point of view, as is also true regarding administration via metered dose
      inhaler or dry powder inhaler. Using a single inhaler might eventually have a
      positive effect on treatment compliance, but there are no confirmatory data yet.
      Despite some clues regarding a presumed agonist effect of ICS and LABAs, there
      are still more doubts than certainties. Even though there are still unanswered
      questions, the data available strongly suggest that the fixed combination of ICS
      and LABAs using the same inhaler is an efficacious, safe and practical approach
      for those asthmatic patients who are not well controlled with low doses of ICS
      alone.

PMID- 12517242
TI  - Thrombolytics: prospects for new agents.
AB  - Thrombolytic therapy revolutionised the management of acute myocardial infarction
      (AMI). The ability to re-establish coronary artery patency with intravenous
      thrombolytic drugs has transformed our therapeutic approach, despite patency
      failures and re-occlusions. However, the established agents are not perfect and a
      number of novel thrombolytic drugs have consequently been developed and
      evaluated. This article reviews the currently available agents, discusses
      available adjunctive therapies and examines the future developments that may
      affect the application of this therapy.

PMID- 12517243
TI  - Current pharmacotherapeutic options for treating deep vein thrombosis.
AB  - The treatment of deep vein thrombosis (DVT) has been evolving over the past 50
      years. Initially, unfractionated heparin (UFH) given subcutaneously every 6 h,
      progressed to constant infusion therapy followed by warfarin, which has become
      the mainstay of therapy. Over the past 12 years, a new therapy, low molecular
      weight heparin (LMWH), has proven to be at least as effective or more effective
      than UFH in the acute treatment of DVT. These drugs are administered
      subcutaneously, are better absorbed and do not require monitoring. LMWHs have
      changed the paradigm of caring for patients with DVT. Finally a number of studies
      with thrombolytic agents have attempted to improve the outcome of DVT by reducing
      clot burden and preventing the sequelae of thrombotic valvular damage. This paper
      will review the management of DVT from the acute phase to long-term management.

PMID- 12517244
TI  - Diagnosis and treatment of endometriosis.
AB  - Endometriosis is a chronic and progressive disease that affects approximately 10%
      of women of reproductive age. Its aetiology remains unknown, however, factors
      such as retrograde menstruation, heredity, impaired immune function and
      environmental toxins have been implicated. Laparoscopy is still considered the
      mainstay for diagnosis, however non-invasive diagnostic methods such as
      transvaginal ultrasound and MRI may also be complementary. Treatment should be
      individualised and current treatment options include medical treatment and
      surgery, however, disease recurrence is common following treatment. Hormonal
      therapy induces atrophy of endometriotic lesions. Conservative surgery may be
      successful in removing visible lesions, however in cases of severe or
      incapacitating illness, removal of the uterus and ovaries may be necessary. In
      such cases, extreme care must be taken to remove all traces of disease.
      Experimental treatments for endometriosis show promising preliminary results and
      include GnRH antagonists, aromatase inhibitors, selective oestrogen receptor
      modulators and mifepristone.

PMID- 12517245
TI  - Frovatriptan: a review.
AB  - Frovatriptan is a potent 5-HT(1B/1D) receptor agonist and has the highest 5
      HT(1B) potency in the triptan class. preclinical pharmacology studies
      demonstrated that frovatriptan is apparently cerebro-selective. In clinical
      pharmacology studies, frovatriptan was shown to have a long-terminal elimination
      half-life of 26 h and to be well-tolerated across a broad dose range of 1-100 mg.
      Frovatriptan has no inhibiting or inducing effects on cytochrome P450 isoenzymes
      and is only slightly bound to plasma proteins; thus it has a low potential for
      drug interactions. No dosage adjustments are necessary based on age or renal or
      hepatic impairment. Efficacy studies show significantly higher response rates
      compared with placebo and the lowest reported range of headache recurrence rates
      in the triptan class. Safety studies show a side effect profile similar to
      placebo. The combination of cerebro-selectivity, long half-life, reliable
      efficacy, low recurrence rates and good tolerability make frovatriptan a valuable
      new choice for acute treatment of migraine. Frovatriptan may be particularly well
      suited to patients with migraine of long duration, those prone to recurrence and
      those troubled by "triptan-type" side effects.

PMID- 12517246
TI  - Clinical use of nifedipine GITS in the treatment of hypertension: an overview.
AB  - Given the major role of elevated blood pressure in the pathogenesis of both
      stroke and coronary heart disease, one of the biggest challenges facing public
      health authorities and medical practitioners is the control of hypertension
      worldwide, both in individual patients and at the population level. The
      prevalence of hypertension increases with age and is nearly 60% in people aged 65
      - 74 years. With increasing age, polymorbidity and polypharmacy usually
      contribute to an increasingly complex approach to manage the respective clinical
      conditions, including the treatment of hypertension. All subgroups of calcium
      channel blockers are effective and well-tolerated in lowering blood pressure.
      They are of demonstrated benefit for the prevention of stroke in elderly patients
      with systolic hypertension. Calcium channel blockers are particularly recommended
      for elderly patients with systolic hypertension and for black patients. The
      nifedipine gastrointestinal therapeutic system (GITS) formulation provides a once
      daily dosing regimen with a continuous and slow release of the drug, resulting in
      a smooth plasma concentration/time profile. The INSIGHT study established that
      nifedipine GITS decreased mortality and morbidity at the same level as standard
      diuretic treatment in hypertensive patients with additional risk factors. A
      subgroup analysis showed that the long-term protective effects of nifedipine GITS
      extended to hypertensive patients with diabetes mellitus and with previous
      myocardial infarction. Two substudies of INSIGHT showed that nifedipine slowed
      the progression of atherosclerosis in carotid arteries (intima-media thickness)
      and coronary arteries (coronary calcium) as compared to diuretic.

PMID- 12517247
TI  - Eprosartan for the treatment of hypertension.
AB  - Antihypertensive agents are proven to reduce the cardiovascular risk of stroke,
      coronary heart disease and cardiac failure. The ideal antihypertensive agent
      should control all grades of hypertension and have a placebo-like side effect
      profile. Angiotensin II (AII) receptor antagonists are a relatively new class of
      antihypertensive agent that block AII Type 1 (AT(1)) receptors, and reduce the
      pressor effects of AII in the vasculature. By this mechanism, they induce similar
      pharmacological effects compared with angiotensin-converting enzyme (ACE)
      inhibitors, resulting in a lowering of blood pressure. However, AII receptor
      blockers differ from ACE inhibitors with respect to side effects, and induce less
      cough, a side effect which may be related to bradykinin or other mediators such
      as substance P. Within the class of AII blockers, eprosartan differs from other
      currently available agents in terms of chemical structure, as it is a non
      biphenyl, non-tetrazole, non-peptide antagonist with a dual pharmacological mode
      of action. Eprosartan acts at vascular AT(1) receptors (postsynaptically) and at
      presynaptic AT(1) receptors, where it inhibits sympathetically stimulated
      noradrenaline release. Its lack of metabolism by cytochrome P450 enzymes confers
      a low potential for metabolic drug interactions and may be of importance when
      treating elderly patients and those on multiple drugs. In clinical trials,
      eprosartan has been demonstrated to be at least as effective in reducing blood
      pressure as the ACE inhibitor enalapril, and has significantly lower side
      effects. Eprosartan is safe, effective and well-tolerated in long-term treatment,
      either as a monotherapy or in combination with other antihypertensive drugs such
      as hydrochlorothiazide.

PMID- 12517248
TI  - Losartan for LIFE in hypertension with left ventricular hypertrophy?
AB  - When ACE inhibitors are used to lower blood pressure to the same degree as beta
      adrenoceptor antagonists or calcium channel blockers, ACE inhibitors do not seem
      to have additional benefits to these agents. In the Losartan Intervention for End
      Point Reduction in Hypertension study (LIFE), losartan was compared to atenolol
      in hypertensives with the additional risk factor of left ventricular hypertrophy
      (LVH). For similar effects on blood pressure, losartan had a greater benefit on
      the primary composite end point (cardiovascular mortality, stroke and myocardial
      infarction) than atenolol in the hypertensives with LVH, including a prespecified
      subgroup of patients with additional diabetes mellitus. Losartan also had a
      greater ability to reverse LVH than atenolol. Thus, losartan should become the
      standard treatment for hypertension when LVH is present.

PMID- 12517249
TI  - Pfizer-Pharmacia: the smart fit for the future.

PMID- 12517250
TI  - Novel therapies for the treatment of inflammatory airway disease.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the
      airways with an underlying inflammatory component. The prevalence and healthcare
      burden of asthma and COPD is still rising and is predicted to continue to rise in
      the current century. The beta-agonists and corticosteroids form the basis of the
      treatments available to alleviate the symptoms of asthma, whereas the treatments
      available for COPD have been shown to have a limited effect on slowing the
      progression of the disease. Asthma and COPD are both in need of novel, safe
      treatments to tackle the underlying inflammation that characterises their
      pathology. The inflammatory processes inherent in asthma and COPD provide the
      opportunity for innovative drug research. This review will outline the new
      approaches and targets being investigated, which may provide opportunities for
      novel therapeutic interventions in these debilitating diseases.

PMID- 12517251
TI  - Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile
      idiopathic arthritis).
AB  - The majority of children with juvenile idiopathic arthritis respond well to
      conventional treatment. However, some children will have a more aggressive
      disease course and will be resistant to standard management. Over the past 20
      years, growth in our understanding of the immunopathogenesis of juvenile
      idiopathic arthritis and related diseases has facilitated significant therapeutic
      advances. In this report, recently released antirheumatic drugs, as well as some
      treatments currently in development, will be discussed. Biological agents, such
      as antiTNF and other cytokines inhibitors, and unique drugs, such as thalidomide,
      provide new opportunities to suppress the inflammation found in severe cases of
      systemic onset juvenile idiopathic arthritis and can obtain a satisfactory
      outcome.

PMID- 12517252
TI  - Recent developments in the pharmacological treatment and prevention of corneal
      graft rejection.
AB  - At present, given the high initial success rate of corneal transplantation
      (although late survival is poor), immunosuppression is often reserved for 'high
      risk' patients. Despite immune privilege, corneal graft rejection remains the
      leading cause of corneal allograft failure. Interpreting the limited and also
      restricted design of most trials, immunosuppressive therapy has not enjoyed the
      success seen in solid organ grafts. This review discusses the limited data
      available whilst proposing newer therapies that have developed as a result of our
      increased understanding of the immunobiology of corneal graft rejection.

PMID- 12517253
TI  - Cannabinoids for gastrointestinal diseases: potential therapeutic applications.
AB  - Delta(9)-Tetrahydrocannabinol (the active ingredient of marijuana), as well as
      endogenous and synthetic cannabinoids, exert many biological functions by
      activating two types of cannabinoid receptors, CB(1) and CB(2) receptors. CB(1)
      receptors have been detected on enteric nerves, and pharmacological effects of
      their activation include gastroprotection, reduction of gastric and intestinal
      motility and reduction of intestinal secretion. The digestive tract also contains
      endogenous cannabinoids (i.e., the endocannabinoids anandamide and 2
      aracidonylglycerol) and mechanisms for endocannabinoid inactivation (i.e.,
      endocannabinoids uptake and enzymatic degradation). Cannabinoid receptors,
      endocannabinoids and the proteins involved in endocannabinoids inactivation are
      collectively referred as the 'endogenous cannabinoid system'. A pharmacological
      modulation of the endogenous cannabinoid system could provide new therapeutics
      for the treatment of a number of gastrointestinal diseases, including nausea and
      vomiting, gastric ulcers, irritable bowel syndrome, Crohn's disease, secretory
      diarrhoea, paralytic ileus and gastroesophageal reflux disease. Some cannabinoids
      are already in use clinically, for example, nabilone and delta(9)
      tetrahydrocannabinol are used as antiemetics.

PMID- 12517254
TI  - Small molecule tyrosine kinase inhibitors: clinical development of anticancer
      agents.
AB  - Numerous small molecule synthetic tyrosine kinase inhibitors are in clinical
      development for the treatment of human cancers. These fall into three broad
      categories: inhibitors of the epidermal growth factor receptor tyrosine kinase
      family (e.g., Iressa trade mark and Tarceva trade mark ), inhibitors of the split
      kinase domain receptor tyrosine kinase subgroup (e.g., PTK787/ZK 222584 and
      SU11248) and inhibitors of tyrosine kinases from multiple subgroups (e.g.,
      Gleevec trade mark ). In addition, agents targeting other tyrosine kinases
      implicated in cancer, such as Met, Tie-2 and Src, are in preclinical development.
      As experience is gained in the clinic, it has become clear that unleashing the
      full therapeutic potential of tyrosine kinase inhibitors will require patient
      preselection, better assays to guide dose selection, knowledge of mechanism-based
      side effects and ways to predict and overcome drug resistance.

PMID- 12517255
TI  - Recent developments in the psychobiology and pharmacotherapy of depression:
      optimising existing treatments and novel approaches for the future.
AB  - Effective antidepressants include monoamine oxidase inhibitors and tricyclic
      antidepressants, selective serotonin re-uptake inhibitors and novel agents,
      including serotonin and noradrenaline re-uptake inhibitors. Although effective,
      current treatments most often produce partial symptomatic improvement (response)
      rather than symptom resolution and optimal functioning (remission). While current
      pharmacotherapies target monoaminergic systems, different symptoms of major
      depressive disorder (MDD) may have distinct neurobiological underpinnings and
      other neurobiological systems are likely involved in the pathogenesis of MDD. In
      this article a review of current pharmacotherapeutic options for MDD, current
      understanding of the neurobiology and pathogenesis of MDD and a review of new and
      promising directions in pharmacological research will be provided. It is
      generally accepted that no single neurotransmitter or system is responsible for
      the dysregulation found in MDD. While agents that affect monoaminergic systems
      will likely continue to be first-line treatments for MDD for the foreseeable
      future, a number of new and novel agents, including corticotropin-releasing
      factor antagonists, substance P antagonists and antiglucocorticoids show
      considerable promise for refining treatment options. In order to better
      understand the neurobiology and treatment response of MDD, it is probable that
      more sophisticated theory-driven typologies of MDD will have to be developed.

PMID- 12517256
TI  - Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of
      type 2 diabetes.
AB  - Incretins are peptide hormones, exemplified by glucose-dependent insulinotropic
      peptide and glucagon-like peptide 1 that are released from the gut in response to
      nutrient ingestion and enhance glucose-stimulated insulin secretion. Incretin
      action is terminated due to N-terminal cleavage of the peptides by the
      aminopeptidase dipeptidyl peptidase IV (DPP-IV). Hence, inhibition of glucose
      dependent insulinotropic peptide and glucagon-like peptide 1 degradation via
      reduction of DPP-IV activity represents an innovative strategy for enhancing
      incretin action in vivo. This review summarises the biology of incretin action,
      the structure, expression and pleiotropic biological activities of DPP-IV and
      provides an overview of the rationale, potential merits and theoretical pitfalls
      in the development of DPP-IV inhibitors for the treatment of type 2 diabetes.

PMID- 12517257
TI  - Developing pharmaceutical treatments for peripheral artery disease.
AB  - Peripheral artery disease (PAD) is a debilitating atherosclerotic disease of the
      lower limbs and is associated with an increased risk of cardiovascular morbidity
      and mortality. Treatment goals should be aimed at providing symptom relief
      (claudication) and reducing the risk of systemic cardiovascular morbidity and
      mortality. In the development of pharmaceutical treatment for PAD, aggressive non
      pharmacological intervention and pharmacological treatment of the risk factors
      associated with PAD should be given. Antiplatelet therapy, aspirin, should be
      given to every PAD patient if there are no contraindications. Should symptoms
      worsen or intolerance to aspirin develop, ticlopidine or clopidogrel would be the
      alternative. Several pharmacological agents have been developed to improve the
      functional state of the claudicant and to relieve the symptoms. Many studied
      drugs have shown either no, small or potential benefit. With future development
      of new drugs for PAD, there is an absolute need for very strict, well-designed
      protocols in order to evaluate the claudication distance and progression of the
      disease, as well as the reduction in cardiovascular morbidity and mortality.

PMID- 12517258
TI  - Recombinant fusion toxins for cancer treatment.

PMID- 12517259
TI  - Islet transplantation for diabetes: current status and future prospects.
AB  - There has been an explosion of interest in developing transplantation strategies
      to replace the islets lost during the normal progression of diabetes. In large
      part, the renewed interest is due to the unprecedented success of the 'Edmonton
      protocol' for Type I diabetics following islet allografting and a modified
      immunosuppressive regimen. While these data provide a clear and unequivocal
      demonstration that islet transplantation is a viable treatment strategy, the
      shortage of suitable donor tissue, together with the debilitating consequences of
      life long immunosuppression necessitate a concerted effort to develop novel means
      to enable islet transplantation on a widespread basis. This review outlines
      several of these possibilities including the development of novel, less toxic
      immunosuppressants, tolerising the host immune system to accept islet
      transplants, developing alternative sources of islet cells via gene therapy, stem
      cell technologies and xenotransplantation, immunoisolation of islets and
      providing local immunosuppression to islet grafts using Sertoli cells. These
      possibilities are highlighted in the context of islet cell transplantation as a
      success, but with need for further refinements before it is a panacea for most
      patients.

PMID- 12517260
TI  - Tissue engineering strategies for in vivo neovascularisation.
AB  - Neovascularisation is a promising alternative therapeutic approach to re
      establish blood flow in ischaemic tissues of patients suffering from coronary
      artery or peripheral artery disease. Often, these patients are not suitable
      candidates for current revascularisation procedures such as coronary angioplasty
      or bypass surgery. Several strategies are presently under investigation to induce
      vascularisation by stimulating the body's natural processes of vasculogenesis,
      angiogenesis and arteriogenesis. These strategies involve transplantation of
      various cell types into the ischaemic site and the delivery of recombinant
      angiogenic agents through direct protein administration or gene transfer. We will
      examine the basic approaches for these neovacularisation strategies and their
      therapeutic potential as demonstrated in animal models and human trials to date.

PMID- 12517261
TI  - Ethical and regulatory aspects of embryonic stem cell research.
AB  - Ethical and regulatory issues concerning embryonic stem (ES) cell research are
      reviewed here a year after the controversy became a public and political issue in
      the US. The background of various issues are examined and the current regulations
      in various countries are reviewed. In the US, the debate is linked with abortion,
      as well as the status of a fetus as a human being, and is politically driven.
      Obtaining stem cells from embryonic tissues involves destruction of the embryo,
      to which objections are raised. Religious beliefs are examined and no serious
      impediments to ES cell research could be identified. Regulations vary from one
      country to another and it is unlikely that there will ever be any universally
      uniform ethical and regulatory standards for ES cell research. Currently, the
      most liberal and favourable environments for ES cell research are in the UK,
      Singapore, Sweden, India, Israel and China. Unless the US liberalises ES cell
      research, it may lose its lead in ES cell research and investments in this area
      may drift to countries with better environments for research. Suggestions are
      offered in this review to improve the ethical environment for ES cell research.

PMID- 12517262
TI  - Immunoregulatory T cells in cancer immunotherapy.
AB  - Many of the tumour antigens targeted by active immunisation strategies are in
      fact self-antigens. Successful anticancer immunotherapy will therefore require
      not only potent methods of T cell activation, but also successful interference
      with mechanisms of immune tolerance that have evolved to prevent tissue
      destruction by autoreactive T cells. In addition to thymic deletion, anergy and
      skewing of T cell cytokine expression, a role for immunoregulatory T cells in the
      maintenance of self-tolerance has been suggested. Suppression of autoreactive T
      cells by regulatory T cells has been suggested to occur by both cytokine and cell
      contact-dependent mechanisms. In murine models, suppression of auto-reactive T
      cells mediated by cell contact has been attributed to a population of
      spontaneously occurring CD4+CD25+ T cells. Cells with similar phenotype and
      function have been found in healthy humans. In murine models, these cells behave
      as regulatory T cells, counteracting autoimmune and inflammatory reactions, and
      have a role in tolerance and in peripheral T cell homeostasis. Of interest for
      cancer immunotherapy is the fact that depleting these cells results in the
      induction of antitumour immune responses, particularly after tumour specific
      vaccination. One hypothesis is that depleting these CD4+CD25+ counter-regulatory
      T cells in humans with cancer will enhance the efficacy of anticancer
      immunisations.

PMID- 12517263
TI  - Genetically modified dendritic cells--a new, promising cancer treatment strategy?
AB  - Dendritic cells (DCs), the most potent antigen-presenting cells (APCs), were
      discovered almost 30 years ago. Due to the priming of antigen-specific immune
      responses mediated by CD4+ and CD8+ lymphocytes, DCs are crucial for the
      induction of adaptive immunity against cancer. Therefore, vaccination of cancer
      patients with DCs presenting tumour-associated antigens (TAAs) have been believed
      to be a promising anticancer strategy. Multiple clinical trials have been carried
      out in order to evaluate the safety and efficacy of cancer vaccines based on
      antigen-pulsed DCs. However, pulsing of DCs with particular peptides has several
      disadvantages: i) short-time duration of antigen-major histocompatability complex
      (MHC) complexes, ii) a requirement for matching defined peptides with MHC
      complexes and iii) exclusive presentation of single antigen epitopes. Application
      of gene transfer technologies in the field of DC-based vaccines made possible the
      development of novel, anticancer immunisation strategies. In several animal
      models, DCs modified with genes encoding TAA or immunostimulatory proteins have
      been shown to be effective in the induction of antitumour immune responses. Based
      on these encouraging results, a first clinical trial of prostate cancer patients
      vaccinated with gene modified DCs has recently been initiated. In this article,
      methods used for genetic modification of DCs and anticancer vaccination
      strategies based on genetically modified DCs are reviewed.

PMID- 12517264
TI  - Advances in gene transfer into haematopoietic stem cells by adenoviral vectors.
AB  - Until recently, the cells of haematopoietic origin were not considered good
      adenoviral (Adv) targets, primarily because they lacked the specific Adv
      receptors required for productive and efficient Adv infections. In addition,
      because of limitations inherent in Adv infections, such as short-term expression
      and a non-integrating nature, their application has been precluded from
      haematopoietic stem cell (HSC) and bone marrow transduction protocols where long
      term expression has been required. Therefore, limited research utilising Adv
      mediated gene transfer into haematopoietic cells had been conducted. With recent
      insights into the critical interactions between adenovirus (Adv) and cells, new
      Adv-mediated gene transduction strategies have now been reported that may
      overcome these limitations. These new strategies include Adv possessing synthetic
      polymer coatings, genetically modified capsid proteins or antibody-redirected
      fibres that can efficiently redirect and retarget Adv to transfer genes into HSC.
      Additionally, new hybrid Advs, engineered with both modified capsid proteins and
      novel cis-acting integration sequences, are also being developed which can
      efficiently deliver and integrate Adv delivered genes into HSC. This is an area
      of research that is now rapidly gaining momentum in terms of techniques and
      applications. Here we review the current status of adenovirus-based vectors as a
      means to achieve high-level gene transfer into haematopoietic cell types.

PMID- 12517265
TI  - Cytochrome P450-based cancer gene therapy: current status.
AB  - Results from a number of preclinical studies have demonstrated that a P450-based
      gene-directed enzyme prodrug therapy (GDEPT) strategy for the treatment of cancer
      is both safe and efficacious. This strategy has now moved forward into the
      clinic. At least two different approaches using different delivery methods
      (retroviral vector MetXia [Oxford BioMedica] and encapsulated P450 expressing
      cells), different cytochrome P450 isoforms (human CYP2B6 versus rat CYP2B1) and
      different prodrugs (cyclophosphamide [CPA] versus ifosfamide [IFA]) have
      concluded Phase I/II clinical trial with encouraging results. In the future, P450
      based GDEPT can potentially be further enhanced by improved vectors for P450 gene
      delivery and disease-targeted promoters for focused gene expression at the target
      site. In addition, there is scope for developing synthetic P450s and their
      respective prodrugs to improve both enzyme kinetics and the profile of the active
      moiety.

PMID- 12517266
TI  - Anti-idiotype antibody vaccine therapy for cancer.
AB  - The use of anti-idiotype (Id) antibodies as vaccines to stimulate antitumour
      immunity is one of several promising immunologic approaches to the therapy of
      cancer. Extensive studies in animal tumour models have demonstrated the efficacy
      of anti-Id vaccines in preventing tumour growth and curing mice with established
      tumours. A number of monoclonal anti-Id antibodies that mimic distinct human
      tumour-associated antigens (TAAs) have been developed and tested in the clinic,
      and demonstrate encouraging results. In general, the antigen mimicry by anti-Id
      antibodies has reflected structural homology in the majority of the cases, and
      amino acid sequence homology in a few of them. The greatest challenge of
      immunotherapy by means of anti-Id vaccines is to identify the optimal anti-Id
      antibody that will function as a true surrogate antigen for a TAA system, and
      ideally will generate both humoral and cellular immune responses. Although
      several clinical studies have shown enhanced survival of patients receiving anti
      Id vaccines, the efficacy of these vaccines will depend on the results of several
      randomised Phase III clinical trials that are currently planned or ongoing.

PMID- 12517267
TI  - Vaccines for Category A bioterrorism diseases.
AB  - Vaccination programmes are very successful as a preventive strategy against many
      infectious diseases which have had a major impact on human morbidity and
      mortality. One of these diseases, smallpox, has been eliminated as a natural
      infection. The recent concern about biological attacks has turned attention to
      the use of an immunisation programme to prevent infection with what are
      considered the most significant potentially harmful biowarfare pathogens. This
      review puts into perspective the available information on current immunisation
      and newer vaccine options for anthrax, smallpox, tularaemia, plague and botulism.

PMID- 12517268
TI  - Reverse vaccinology: a genome-based approach for vaccine development.
AB  - During the last century several approaches have been followed for the development
      of vaccines. These include live-attenuated viruses and bacteria, killed
      microorganisms and the subunit vaccines [1]. With the introduction of recombinant
      DNA technologies, new approaches have been exploited for vaccine manufacturing.
      However, the major problem remains the rapid identification of highly immunogenic
      and protective antigens suitable for vaccine development, which still relies on
      standard biochemical and microbiological techniques. The advent of genomics has
      greatly contributed to providing a new impulse to the microbial field. The
      complete genomic sequence of a human pathogen represents a new unexploited field,
      to be used for the design of novel vaccines and antimicrobial drugs. In the case
      of meningococcus B, four decades of continuous efforts, using conventional
      technologies of purifying antigens from the microorganism, had not been
      sufficient to deliver an effective and universal vaccine. It was therefore
      decided to obtain the genomic sequence of serogroup B Neisseria meningitidis
      (MenB) and use this information to identify vaccine candidates. This approach was
      named "reverse vaccinology"[2].

PMID- 12517269
TI  - Immunological approaches as therapy for Alzheimer's disease.
AB  - The pathology of Alzheimer's disease (AD) shows a significant correlation between
      beta-amyloid peptide (AbetaP) conformation and the clinical severity of dementia.
      For many years, efforts have been focused on the development of inhibitors of
      beta-amyloid (Abeta) formation and its related neurotoxic effects. The author has
      developed a new concept showing that site-directed antibodies may modulate
      formation of Abeta. The performance of anti-Abeta antibodies in transgenic mice
      models of AD showed that they are delivered to the central nervous system (CNS),
      preventing in vivo formation of Abeta. Moreover, these antibodies dissolve Abeta
      plaques and protect the mice from learning difficulties and age-related memory
      deficits. Experimental active immunisation with Abeta (1-42) in humans has been
      stopped in Phase II of their clinical trials. However, several new preparations,
      able to provide antibodies against Abeta by either active or passive routes, have
      been formulated and at least one of these is likely to reach clinical testing.
      These data support the hypothesis that AbetaP plays a central role in AD and
      antibodies which modulate Abeta conformation may lead to immunotherapy of the
      disease.

PMID- 12517270
TI  - Dendritic cell-based vaccines and therapies for cancer.
AB  - Dendritic cells (DCs) are the most potent professional antigen-presenting cells
      (APCs), and are capable of stimulating naive T cells and driving primary immune
      responses. Due to this unique property, DCs represent both vectors and targets
      for immunological intervention in numerous diseases and are optimal candidates
      for vaccination protocols in cancer. This review provides an overview of DC
      immunobiology and the integration of these important APCs in immunotherapies for
      cancer.

PMID- 12517271
TI  - Antigen-based immune modulation: DNA vectors and beyond.
AB  - The ultimate goal for autoimmune immunotherapy is to achieve a specific
      downregulation or modification of autoaggressive immune responses while leaving
      in place the normal repertoire, capable of mediating antimicrobial responses. A
      multitude of preclinical studies, particularly during the last 15 years, raised
      hopes that self-antigens could be used to achieve the goal of specific immune
      modulation. Difficulties associated with the translation of this concept to the
      clinic revealed inherent limitations of antigen-based immune modulation. To
      increase the efficiency of antigen-dependent immune modulation, researchers
      started to investigate novel vectors for antigen delivery. Plasmid vectors, as
      opposed to protein antigens or peptides, have the ability to trigger prolonged
      production of limited amounts of antigen in the periphery. However, one
      complicating factor may be the inherent "danger" signal stimulated by the nature
      of the unmethylated CpG motifs on bacterial plasmid. Currently, various
      approaches are being explored to improve the efficacy of response while
      ameliorating the safety concerns of plasmids as immunotherapeutic tools. This
      manuscript offers a perspective on such efforts and outlines how the knowledge
      accumulated in the process will help scientists advance to the next generation of
      immunotherapeutics.

PMID- 12517272
TI  - Oncolytic adenoviruses for treatment of brain tumours.
AB  - Standard therapies are not capable of curing patients with malignant glioma; more
      than 90% of patients die within 2 years after diagnosis. Gene therapy appeared as
      a promising new approach for this disease. However, results of clinical trials
      with replication deficient viral vectors were disappointing. The main reasons
      being poor transduction efficiency of adenovirus towards glioma cells and limited
      spread and distribution of the vector in the tumour. With the increasing
      knowledge of viral genetics and its functions, an attractive alternative tool to
      kill malignant glioma cells has been developed: Replicating adenovirus as an
      oncolytic agent. This type of therapy, also referred to as virotherapy, has the
      potential to overcome some of the limitations connected with replication
      deficient adenoviral vectors. In this review the authors describe the latest
      developments in strategies that are being used to create a tumour- or glioma
      selective replicating adenovirus. Special attention is given to the methods of
      viral delivery to an infiltrating tumour in the brain, regarding optimal dose and
      toxicity. Furthermore, the role of conventional antitumour treatments, such as
      irradiation and chemotherapy, in enhancing the effect of virotherapy is being
      emphasised.

PMID- 12517273
TI  - Recent developments in antiangiogenic therapy.
AB  - The use of antiangiogenic therapy is gaining momentum as a novel treatment for a
      number of conditions, ranging from cancer to psoriasis. This has stemmed from
      research in the early 1970s showing that the formation of new blood vessels by
      pre-existing endothelial cells is essential in tumour growth and progression.
      However, although antiangiogenic therapy was hailed as a new avenue of treatment
      for cancer, initial clinical data have been disappointing. This has led to the
      reassessment of antiangiogenic therapy for cancer, and new strategies have been
      proposed to increase the efficacy of these agents in this setting. Angiogenesis
      has also been implicated in other conditions that are notoriously difficult to
      treat, such as arteriosclerosis, arthritis, psoriasis and diabetic retinopathy.
      Increased understanding of the angiogenic process, the diversity of its inducers
      and mediators, appropriate drug schedules and the use of these agents with other
      modalities may lead to radically new treatment regimens for many of these
      conditions. The role of angiogenesis in different pathological settings, and
      emerging antiangiogenic agents currently in preclinical and clinical studies are
      discussed in this review. However, while potential benefits are profound,
      limitations of antiangiogenic therapy have also been identified, suggesting that
      there is also a need for caution in applying these compounds to the clinical
      setting.

PMID- 12517274
TI  - Alpha-L-iduronidase and enzyme replacement therapy for mucopolysaccharidosis I.
AB  - Mucopolysaccharidosis I (McKusick 25280, Hurler syndrome, Scheie syndrome) is
      caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase (EC
      3.2.1.76) and results in a failure to degrade the glycosaminoglycans, dermatan
      sulfate and heparan sulfate. Mucopolysaccharidosis I patients present within a
      spectrum of clinical phenotypes, where Hurler and Scheie syndromes represent the
      two extremes. In the 80 or more years since the discovery of
      mucopolysaccharidosis I, the molecular defect has been defined, the alpha-L
      iduronidase protein purified and characterised, the alpha-L-iduronidase (IDUA)
      gene cloned, molecular genetic studies performed and expression systems
      developed. These advances have allowed the development of alpha-L-iduronidase
      enzyme replacement therapy as a treatment strategy for mucopolysaccharidosis I
      patients. Using animal models of mucopolysaccharidosis I, the efficacy of alpha-L
      iduronidase replacement therapy has been evaluated and justified the initiation
      of human clinical trials in mucopolysaccharidosis I patients. Phase I/II and
      Phase III clinical trials have recently been conducted and demonstrated that this
      therapy is effective in treating patients with the attenuated forms of
      mucopolysaccharidosis I (that is, little or no neuronal involvement). Further
      development of this technology is required to effectively treat the problem sites
      of neuronal and skeletal pathology, present in severe Hurler syndrome patients.

PMID- 12517275
TI  - Darbepoetin alfa: a new therapy for the management of anaemia associated with
      chronic kidney disease.
AB  - Darbepoetin alfa (Aranesp, Amgen, Inc., Thousand Oaks, California) is a new
      erythropoietic protein that corrects anaemia associated with chronic kidney
      disease (CKD) in the majority of patients. Darbepoetin alfa contains five N
      linked carbohydrate chains compared with three in recombinant human
      erythropoietin (rHuEPO). The two additional sialic acid-containing carbohydrate
      chains prolong the serum half-life of darbepoetin alfa, resulting in greater
      biological activity and a reduced dosing frequency compared with rHuEPO. Clinical
      studies in patients with CKD have demonstrated that darbepoetin alfa is effective
      in correcting anaemia in rHuEPO-naive patients and in patients who have been
      converted from rHuEPO therapy. Darbepoetin alfa provides long-term maintenance of
      haemoglobin levels when administered once weekly or once every other week, with
      the possibility of once-monthly dosing in some patients. Darbepoetin alfa is well
      tolerated and has a safety profile similar to that of rHuEPO. Owing to its half
      life being three times longer than rHuEPO, darbepoetin alfa can be administered
      at an extended dosing interval, without compromising efficacy. Lessfrequent
      dosing has potential benefits for both patients with CKD and healthcare
      providers. These benefits include reduced visits to the clinic, fewer injections
      and a reduced demand on staff and treatment facilities.

PMID- 12517276
TI  - Pegfilgrastim.
AB  - Granulocyte colony stimulating factor (G-CSF) has proven efficacy in the
      prophylaxis of chemotherapy induced neutropenia and is associated with a
      reduction in the duration of neutropenia, febrile neutropenia, hospitalisation
      and intravenous antibiotic use. It is an effective mobiliser of peripheral blood
      progenitor cells and is used in many countries to mobilise and provide a source
      of stem cells for autologous and allogeneic bone marrow transplantation. The
      longevity of G-CSF action is limited by its short half-life, necessitating daily
      injections. Pegfilgrastim (Neulasta, Amgen, Inc.) is a novel form of filgrastim
      (G-CSF) with a sustained duration of action. Single dose pegfilgrastim has been
      shown to be as safe and effective as daily filgrastim in reducing the incidence
      of chemotherapy induced neutropenia. Pegfilgrastim provides clinical and quality
      of life benefits for patients as a result of its once per cycle administration.
      It is licenced in the US for use in the prophylaxis and treatment of chemotherapy
      induced neutropenia. Clinical trials to evaluate its ability to mobilise
      peripheral blood progenitor cells are ongoing.

PMID- 12517277
TI  - Biological therapy in transplantation: an update from the 19th International
      Congress of the Transplantation Society.
AB  - With the recent upsurge in pharmaceutical drugs changing the 'playing field' of
      transplantation therapeutics, the role of old agents, such as polyclonal
      antilymphocyte globulins and anti-CD3 monoclonal antibodies, is being revisited,
      with suggestions of using different, lower dose regimens to spare the use of
      other drugs. Similar suggestions have been made for the newer recombinant anti
      CD25 antibodies. Numerous experimental models and a few early clinical models are
      evolving to try to determine the place of a range of biological reagents with
      specificities for novel targets. These include the costimulatory ligand-receptor
      pairs, such as CD40-CD154 and CD80/CD86-CD28, CD52 and CD45. The role of these
      newer agents is far from clear, but some of these early studies are very
      promising.

PMID- 12517278
TI  - Pharmacogenomics and reducing the frequency of adverse drug events.

PMID- 12517279
TI  - Shaping biological knowledge.

PMID- 12517280
TI  - Diabetic gene linked with fivefold greater risk of developing heart disease.

PMID- 12517281
TI  - "Chemogenomics: tools for protein families" and "Chemical genomics: chemical and
      biological integration".

PMID- 12517282
TI  - Splicing 2002: RNA splicing in human pathology.

PMID- 12517283
TI  - Pharmacogenomics in the treatment of narcolepsy.
AB  - Narcolepsy is a neurological disorder characterized by excessive daytime
      sleepiness and cataplexy. Available treatments of narcolepsy include stimulants
      and antidepressants but the recent discovery of orexin/hypocretin deficiency in
      narcolepsy opens up new perspectives. Narcolepsy is a complex disorder involving
      genetic, immune and environmental factors. Although only a strong association is
      found with the HLA DQB1*0602 gene, other genetic susceptibility factors might be
      involved. Among these, the functional polymorphism of the catechol-O
      methyltransferase (COMT) gene is critically involved in the severity of
      narcolepsy and in the response to the stimulant modafinil. Other pharmacogenetic
      targets include the orexinergic, noradrenergic and possibly the serotonergic
      pathways.

PMID- 12517284
TI  - Pharmacogenetic aspects of bipolar disorder.
AB  - This paper reviews current knowledge of genetic factors in the treatment of
      bipolar disorder. Most studies to date have investigated genetic differences
      between responders and non-responders to lithium. The most provocative findings
      have been obtained in studies of serotonin transporter gene. Another promising
      application of pharmacogenetic research is the identification of subgroups of
      bipolar disorder defined by response (or non-response) to pharmacological
      treatments. Such subgroups could be used to define more homogeneous patient
      populations for gene-mapping studies.

PMID- 12517285
TI  - Analyzing microarray data using cluster analysis.
AB  - As pharmacogenetics researchers gather more detailed and complex data on gene
      polymorphisms that effect drug metabolizing enzymes, drug target receptors and
      drug transporters, they will need access to advanced statistical tools to mine
      that data. These tools include approaches from classical biostatistics, such as
      logistic regression or linear discriminant analysis, and supervised learning
      methods from computer science, such as support vector machines and artificial
      neural networks. In this review, we present an overview of another class of
      models, cluster analysis, which will likely be less familiar to pharmacogenetics
      researchers. Cluster analysis is used to analyze data that is not a priori known
      to contain any specific subgroups. The goal is to use the data itself to identify
      meaningful or informative subgroups. Specifically, we will focus on demonstrating
      the use of distance-based methods of hierarchical clustering to analyze gene
      expression data.

PMID- 12517287
TI  - Techniques patents for SNP genotyping.
AB  - Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic
      variation in the human genome, accounting for more than 90% of all differences
      between individuals. Many complex phenotypes in humans have a significant genetic
      component and most of the variability is therefore likely to stem from
      differences in patterns of SNPs. Association studies involving the large-scale
      analysis of SNPs can help to identify genes affecting many human phenotype
      variations, including complex diseases and drug responses. SNPs therefore play a
      major role in all stages of the drug development process, from target
      identification through to clinical trials. SNPs are also the basis of
      pharmacogenomics, the tailoring of medicines to suit an individual's genome.
      Given the potential impact of SNPs on healthcare, the biotechnology industry has
      focussed urgently on the development of high-throughput methods for SNP
      genotyping. All genotyping methods are a mix and match of different allele
      discrimination and signal detection technologies and as such may represent the
      intellectual property of several individuals or organizations. In this review, we
      explore the patent issues surrounding SNP genotyping and how this is influencing
      large scale, commercially valuable projects involving SNPs.

PMID- 12517286
TI  - Genetics of blood pressure, hypertensive complications, and antihypertensive drug
      responses.
AB  - Hypertension is the most prevalent, treatable risk factor for diseases of the
      heart, brain and kidneys. In this review, we discuss advances in understanding of
      the genetics of blood pressure regulation, the development of hypertensive
      complications and the pharmacodynamics of antihypertensive drug responses.
      Discovery of single gene mutations that cause hypertension or hypotension in
      humans suggests that the common final pathway for regulation of blood pressure
      level is via alterations in renal sodium handling. Based on a working hypothesis
      that common genetic variations contributing to blood pressure variation in the
      population may also act on this same pathway, we summarize supporting evidence
      emerging from linkage and selected association studies of candidate genes-
      including those encoding components of the renin-angiotensin-aldosterone system,
      the epithelial sodium channel, adrenoceptors, G protein subunits, and other
      cellular signaling mediators and modifiers. We proceed to distinguish ischemic
      target organ complications due to arteriolosclerotic changes of the
      microvasculature from those due to atherosclerosis involving larger conduit and
      capacitance arteries. Using the example of subcortical white matter ischemia of
      the brain, we propose that interindividual variation in the arteriolosclerotic
      complications is more likely than atherosclerotic complications to be related to
      the same genetic (and environmental) mechanisms that contribute to hypertension.
      We conclude by summarizing the state-of-the-art of antihypertensive
      pharmacogenetics, which has succeeded in rejecting the null hypothesis that
      genetic variation does not influence blood pressure or protective target organ
      responses to drug therapy. In each of the three areas covered in this review, we
      indicate the many remaining obstacles to the routine clinical use of genetic
      measurements in the diagnosis, evaluation and treatment of hypertension.

PMID- 12517288
TI  - Patentability and maximum protection of intellectual property in proteomics and
      genomics.
AB  - The patenting of inventions in the proteomics and genomics fields has been
      prolific in the last few years and should continue in that vein for some years to
      come. The ingenuity by which inventions can be claimed increases so that even
      computerized methods for finding useful drugs based on the underlying genomic and
      proteomic information find their way into patents. However, with the increasing
      number of patents invalidated and the increasing number of exceptions to patent
      infringement; the value of new biotechnology patents is being whittled away.
      First, it may be hard to find potential infringers who improperly practice the
      claimed invention. Second, these potential infringers may practice in areas of
      the world where there is no patent protection. Third, the practice may be held by
      a court not to be infringing activity because it has as its aim the development
      of a new drug. Finally, the claims may be held invalid for lack of written
      description or enablement as the courts find mechanisms or reasons to narrow the
      allowable claims. With this setting, we must consider what can be done to best
      protect this new generation of inventive activity. Moreover, we must consider the
      possible demise of the drug pipeline should this trend to narrow protection
      continue.

PMID- 12517289
TI  - Nuffield Council on Bioethics consultation.
AB  - The possibility of using genetic analysis to predict response to medicines has
      led some to make the optimistic claim that personalized medicine--"the right
      medicine, for the right patient, at the right dose"--will only be a matter of
      time. Indeed, pharmacogenetic tests could be one of the earliest practical
      applications that information from the Human Genome Project will have on our
      lives. Many patients experience side effects from medicines, and the use of
      pharmacogenetics in the drug discovery process has the potential to improve
      efficacy and safety of some treatments. However, both the research and the
      clinical applications raise ethical, legal, social and regulatory issues that
      need to be addressed before targeted prescription becomes reality. The Nuffield
      Council on Bioethics has established a Working Party to consider these issues and
      has recently issued a consultation document on the subject.

PMID- 12517290
TI  - DxS Ltd.
AB  - DxS is a pharmacogenomics business operating at the interface between genetic
      diagnostics and the pharmaceutical industry. The company strategy is to enable
      pharmacogenomics by the provision of genetic analysis services to the healthcare
      sector. The services provide support for drug discovery, drug development and
      also drug marketing via the introduction of "personalized medicines". Rather than
      specialize in a particular field of medicine, DxS has chosen to operate on a fee
      for service basis and concentrate on the provision of exceptional levels of
      customer, technical and logistical support to facilitate the development and
      introduction of pharmacogenomics. A major focus is the provision of genetic
      analysis services to support clinical trials and consequently the service
      operation is carried out under stringent quality systems. The business is also
      developing the Genetwork--a global alliance of diagnostic service laboratories to
      provide the diagnostic genotyping needed to implement personalized medicine.

PMID- 12517291
TI  - Three-field dissection for squamous cell carcinoma in the thoracic esophagus.
AB  - An esophageal cancer has frequent metastasis in the cervical and upper
      mediastinal lymph nodes, in particular along the recurrent nerves.
      Cervicothoracoabdominal three-field dissection is the most radical and rational
      lymphadenectomy procedure based on this evidence. During three-field dissection,
      the nodes along the recurrent nerves from the neck to the mediastinum are more
      meticulously resected than during any other procedure of radical lymphadenectomy.
      A consensus has been obtained that complete resection of the recurrent nerve
      nodes improves the survival rates of patients with cancer in each of the various
      locations of the thoracic esophagus, and that resection of the supraclavicular
      and internal jugular nodes improves the survival rates of patients with cancer in
      the upper thoracic esophagus. There is, however, still some controversies over
      whether or not resection of the supraclavicular and internal jugular nodes
      improves the survival rates of patients with cancer in the middle or lower
      thoracic esophagus. Moreover, there remains many controversies over the
      indication for three-field dissection regarding metastasis-positivity in the
      lymph nodes, the numbers of the metastasis-positive nodes, the stage, surgical
      risks and other aspects. Large randomized prospective studies are needed to
      accumulate conclusive evidence for the benefits of three-field dissection.

PMID- 12517292
TI  - Necessity of screening for multiple primary cancers in patients with esophageal
      cancer.
AB  - This study divided patients with esophageal cancer and multiple primary cancers
      into two groups, a head and neck cancer (HNC) group and a non-head and neck
      cancer (NHNC) group. These groups were then evaluated on the basis of clinical
      and pathological studies. Among 92 patients with esophageal cancer as one of
      multiple primary cancers, 38 (41.8%) were assigned to the HNC group. The
      following characteristics distinguished patients in the HNC group from those in
      the NHNC group: (1) younger age; (2) shorter interval between diagnosis of
      metachronous cancers; (3) many displayed superficial esophageal cancer. Among the
      cases in which esophageal cancer was discovered synchronously with head and neck
      cancer, head and neck cancers were discovered before esophageal cancer; and (4)
      many patients displayed esophageal dysplasia, and many had multiple esophageal
      cancers. In the present study, we demonstrated the necessity of screening for
      multiple primary cancers in patients with esophageal cancer.

PMID- 12517293
TI  - Effects of leukocyte-depleted reoxygenation on endothelial and ventricular
      function: with observation of a short time period.
AB  - Postoperative myocardial global dysfunction causes mortality and morbidity in
      cyanotic congenital defects. This study investigates whether leukocyte depletion
      during coronary perfusion following reoxygenation can maintain endothelial and
      myocyte function, or less oxidant damage in a porcine neonatal model. After 30
      minutes hypoxemia, 13 piglets underwent 60 minutes reoxygenation. The aorta was
      clamped and coronary reperfusion was either with normal blood (N=6), or leukocyte
      free blood by an inline filter (N=7). Cardiac function and endothelial response
      were assessed before and after cardiopulmonary bypass (CPB). Contractile recovery
      was improved by leukocyte depletion. Additionally, the antioxidant reserve
      capacity reserved more (534 36 versus 772 91; p<0.05) than reoxygenation without
      a leukocyte-depleting filter. Leukocyte depletion returned more extreme
      relaxation to acetylcholine (71.8 20.4% versus 41.2 9.8%; p<0.05), but did not
      change the endothelium-independent relaxation to sodium nitroprusside in either
      group. Activated leukocytes release oxygen free radicals that play a role in
      deterioration of the endothelial/myocardial function after reoxygenation and this
      deterioration in cyanotic heart diseases may be avoided by the use of the
      leukocyte-depleting filter.

PMID- 12517294
TI  - Avoiding the pump in tricuspid valve endocarditis--vegetectomy under inflow
      occlusion.
AB  - BACKGROUND: Surgical treatment of tricuspid valve endocarditis (TVE) ranges from
      vegetectomy to valve replacement with the use of cardiopulmonary bypass (CPB),
      accompanied by risks of systemic and lung complications. We present our
      experience with tricuspid valve vegetectomy under inflow occlusion without CPB.
      METHODS: Between July 1998 and July 2001, seven patients with a mean age of 26
      years underwent tricuspid valve vegetectomy under vena caval inflow occlusion
      (VCIO). Five patients were intravenous drug users. None of them had left-sided
      heart valve involvement. The clinical indications for operating were recurrent
      septic pulmonary emboli with significant bilateral lung infiltrates and
      intractable infection with signs of severe systemic sepsis, despite treatment
      with appropriate intravenous antibiotics for a mean duration of 126 hours. The
      echocardiographic indication was very large localized >1 cm vegetations in all
      patients. Six patients had methicillin sensitive staphylococcus aureus and one
      had streptococcus viridans positive blood cultures. Five patients had
      postoperative high volume veno-venous hemofiltration (HVVF). RESULTS: There were
      no deaths. VCIO time did not exceed 2 minutes (range time was 45 seconds to 2
      minutes). All patients had resolution of sepsis and improvement in respiratory
      status within 48 hours. Five patients had trivial and two moderate tricuspid
      regurgitation. Six patients were discharged home within 14 days with no long-term
      sequelae. One patient required long-term dialysis for renal failure. One patient
      required a late thoracotomy for drainage of a loculated empyema. CONCLUSIONS:
      Tricuspid valve vegetectomy can be performed safely under VCIO. HVVF promotes
      removal of inflammatory mediators, thus improving recovery.

PMID- 12517295
TI  - Radial artery 2000--risk analysis of mortality for coronary bypass surgery with
      radial artery.
AB  - BACKGROUND: The aim of this study is to review our experience with using more
      than 2,000 RAs over the last seven years, and to assess the medium-term outcome
      in terms of morbidity and mortality. METHODS: Between June 1994 and June 2001, a
      total of 2,024 RAs have been used in 1,613 patients. The mean duration of follow
      up was 40.1 months and ranged from one to 88 months. We assessed the results of
      postoperative mortality and morbidity, RA graft patency, coronary event free
      rate, and actuarial survival rate. Specifically, the independent predictors of
      early and late mortalities were examined. RESULTS: Perioperative myocardial
      infarction was indicated in 0.8%, stroke in 1.6%, respectively. Overall hospital
      mortality was 35 patients (2.4%). RA patency rate was 98.1%. Coronary event free
      rate and actuarial survival rates at seven years were 99.6% and 95.1%,
      respectively. Multivariate logistic regression analysis detected an ejection
      fraction of less than 30% (p=0.0009), re-exploration (p=0.02), and stroke
      (p=0.03) as significant independent predictors of operative mortality. The use of
      saphenous vein graft (p=0.0417) and renal impairment (p=0.0045) were significant
      independent predictors of late mortality. CONCLUSIONS: Our seven-year experience
      of CABG with RA suggested that the use of RA was safe and had excellent results
      in postoperative graft patency and low incidence of complications. This study
      suggested that the use of RA instead of the saphenous vein graft made a better
      outcome for late survival in the patients undergoing CABG.

PMID- 12517296
TI  - Concomitant cholecystectomy and coronary artery bypass.
AB  - INTRODUCTION AND METHODS: Cholelithiasis is a common disorder which may be
      present with coronary artery disease. Concomitant cholecystectomy and coronary
      artery bypass grafting (CABG) was performed in selected patients and
      retrospective study was performed to verify the safety of the concomitant
      surgery. RESULTS: A total of 55 patients (41 males and 14 females, mean age 64.6
      8.7 years) underwent concomitant cholecystectomy and CABG between 1992 and 2001
      at the Shin-Tokyo Hospital Group. Exclusion from concomitant surgery was
      choledocholithiasis and/or acute cholecystitis. Cholecystectomy was performed via
      an upper abdominal incision extending the mid-sternal incision. In 48 patients
      (87.3%), the gastroepiploic artery (GEA) was used for coronary revascularization.
      The mean number of bypass grafts was 3.6 1.2. The mean operative time, intubation
      period, ICU stay, and postoperative hospital stay were 376 minutes, 15.6 hours,
      3.9 days, and 23.0 days, respectively. Postoperative feeding was resumed 1 day
      after extubation. No intra-abdominal complications, delays in feeding, abdominal
      wound complications or postoperative bowel obstruction were observed.
      CONCLUSIONS: Concomitant surgery of cholecystectomy and CABG did not increase the
      postoperative complications, and it is a feasible procedure of choice.

PMID- 12517297
TI  - Preoperative parameters predicting the postoperative course of endoventricular
      circular patch plasty.
AB  - It is necessary that preoperative factors predicting the postoperative course be
      easily and precisely documented. We investigated the preoperative predictors and
      defined the indications of endoventricular circular patch plasty (EVCPP) in
      patients with ischemic cardiomyopathy (ICM). Between October 1997 and May 2001,
      22 patients (19 males and 3 females; mean age 63.4 years, range 50 to 75 years)
      with ICM underwent EVCPP. Only one patient underwent EVCPP alone. Coronary artery
      bypass grafting (CABG) associated with EVCPP was performed in 18 patients (82%).
      Twenty-two patients were divided into two groups according to the outcome after
      surgery. Group A consists of three patients who died after surgery and two who
      showed no clinical improvement after surgery. Group B comprises 17 patients who
      showed clinical improvement in terms of New York Heart Association (NYHA)
      functional class, freedom from angina or congestive heart failure. The left
      ventricular systolic dimensions (LVDs) in group A was significantly longer
      compared with that in group B (p=0.02, 5.8 versus 4.8 cm). They were not
      statistically different in other variables between the two groups. We analyzed 10
      preoperative variables which are categorized as crucial predictors of
      postoperative course. We found statistically significant differences in LVDs
      greater than or equal to 5.5 cm and fractional shortening (FS) less than or equal
      to 15% (p=0.0393, p=0.0207) as well as an increased odds ratio (13, 18.6667,
      respectively) between A and B groups. In the present study, LVDs and FS
      demonstrated the dimensional alteration of the cardiac basal segment, and
      identify the degree of contraction in the nonaneurysmal portion of the ventricle
      which will remain after surgery. Therefore, LVDs and FS indicating the functional
      reserve of the basal segment of the ventricle after EVCPP may be the most
      important parameters predicting the postoperative course.

PMID- 12517298
TI  - Surgical treatment of aortic arch aneurysm combined with coronary artery
      stenosis.
AB  - OBJECTIVE: We present operative results of aortic arch aneurysm associated with
      coronary artery stenosis, and evaluate the operative risk of graft replacement of
      the aortic arch and concomitant coronary artery bypass grafting (CABG). PATIENTS
      AND METHODS: From January 1991 to December 2001, we treated 16 patients with
      aortic arch aneurysm and coronary artery stenosis. The patients, 3 women and 13
      men (study group) ranged from 58 to 79 years of age, average 68.1 5.3 years. With
      the aid of deep hypothermic cardiopulmonary bypass, we performed graft
      replacement of the aortic arch aneurysm and concomitant CABG. We bypassed 31
      coronary arteries. The bypass grafts included saphenous vein (n=16), left
      internal thoracic artery (n=4), right internal thoracic artery (n=1), right
      gastroepiploic artery (n=5) and inferior epigastric artery (n=2). The number of
      bypassed coronary arteries per patient ranged from 1 to 3, average 2.1
      0.8/patient. A comparative study was performed between the study group and a
      control group of patients (n=39) who had undergone only graft replacement of the
      aortic arch. RESULTS: There was no significant difference between the two groups
      regarding: operation time, cardiopulmonary bypass time, cardiac arrest time,
      intraoperative bleeding volume, and early mortality rate. However, in the
      patients (n=4) of the study group who had undergone total arch graft replacement
      with three vessel CABG, the cardiopulmonary bypass time was significantly longer
      than that of the patients in the control group who underwent total arch graft
      replacement (n=19, P<0.05). Two of the 16 study group patients died in the early
      postoperative period, resulting in 12.5% early mortality rate. In the control
      group, four of 39 patients (10.3%) died in the early postoperative period.
      CONCLUSIONS: CABG combined with graft replacement of the aortic arch does not
      increase operative risk when the number of bypassed vessels is within two
      vessels, but may increase risk when three or more vessels are bypassed.

PMID- 12517299
TI  - Surgical treatment of Budd-Chiari syndrome induced by Behcet's disease.
AB  - OBJECTIVE: Although Budd-Chiari syndrome in Japanese is usually chronic, and of
      unknown etiology and idiopathic, Behcet's disease is rare as an underlying
      disorder of Budd-Chiari syndrome in Japanese. To clarify the Behcet-induced Budd
      Chiari syndrome, the clinical course and pathologic findings of patients with
      Behcet-induced Budd-Chiari syndrome were compared with those of patients with
      idiopathic Budd-Chiari syndrome. PATIENTS AND METHODS: We treated 45 patients (15
      women and 30 men) with our devised surgical procedure. With normothermic partial
      bypass, the occluded vena cava and hepatic veins were reopened. The age of the
      patients ranged from 24 to 76 years (mean, 48.9 13.0 years). In two patients,
      Budd-Chiari syndrome was induced by Behcet's disease (Behcet group). The other 43
      patients (control group) had no distinct underlying disorder. The Behcet group
      was compared to the control group with regards to (1) onset of symptoms and
      duration of illness prior to medical treatment, (2) preoperative laboratory data
      including liver function, (3) intraoperative findings, (4) microscopic findings
      of liver tissue, and (5) postoperative course. RESULTS: (1) In the Behcet group,
      duration of illness from diagnosis to surgical treatment was markedly shorter
      (P=0.027, 8.5 months vs. 10.1 10.6 years). (2) The preoperative laboratory data
      of liver function were similar in both groups with moderately impaired hepatic
      function. (3) The Behcet group had no patent hepatic vein (P=0.025 vs. 1.22
      0.57). (4) Microscopic examination of the liver tissue showed liver cirrhosis or
      liver fibrosis in the control group, and centrilobular marked congestion only in
      the Behcet group. (5) During hospitalization, one patient of the control group
      died due to preoperative severe hepatic failure. One patient with Behcet's
      disease underwent reoperation due to reocclusion by Behcet-induced vasculitis,
      and the other died of peritonitis by intestinal Behcet's disease. CONCLUSION: In
      Budd-Chiari syndrome in Japanese, the Behcet-induced Budd-Chiari syndrome had an
      acute clinical course, and its postoperative prognosis depends on the prognosis
      of the Behcet's disease.

PMID- 12517300
TI  - The role of antibiotic treatment alone for the management of Brucella
      endocarditis in adults: a case report and literature review.
AB  - Endocarditis is a rare complication of brucellosis but it is the main cause of
      the mortality in this disease. The accepted treatment for Brucella endocarditis
      (BE) is a combination of valve replacement and antibiotics. Conservative
      antibiotic treatment alone is not recommended by most of the authors as it is
      considered ineffective and increase the risk of fatality. In our literature
      search, we found 14 adult patients with BE treated only with antibiotics with a
      favorable outcome. In this report, we described a patient treated with
      antibiotics alone and reviewed the literature. Depending on the data from the
      growing literature and our patient we suggest that in selected patients with BE
      who do not have congestive heart failure, valvular destruction, abscess
      formation, or a prosthetic valve, conservative antibiotic treatment may be a
      valid alternative to surgery.

PMID- 12517301
TI  - Treatment of refractory coronary vasospasm during cardiopulmonary bypass with
      compulsory coronary perfusion.
AB  - Coronary vasospasm is still a devastating complication during cardiac surgery. We
      report on a case of intractable coronary vasospasm in a 45-year-old male during
      coronary bypass surgery refractory to drugs and intra-aortic balloon pumping
      (IABP). Under cardiopulmonary bypass (CPB) support, the aorta was again cross
      clamped and the aortic root was compulsorily perfused with pump blood using a
      small pump for infusion of cardioplegia. Vasodilators were administered through
      the perfusion line. Coronary vasospasm was dramatically resolved. He was then
      successfully weaned from CPB and recovered without further incidents.

PMID- 12517302
TI  - New surgical technique of left ventricular free wall rupture: double patch
      sealing method.
AB  - We experienced two cases of left ventricular free wall rupture (LVFWR) following
      acute myocardial infarction (AMI). Case 1, with the blowout type of LVFWR was
      initially closed by direct suture, followed by hemostasis using a double patch
      sealing method (DPS) by which the tear was doubly sealed with large and small
      bovine pericardium patches to which GRF glue was applied. Case 2 with the oozing
      type of LVFWR was treated only using DPS. Complete hemostasis was achieved in
      both cases, and aneurysmal dilatation or constrictive heart failure were not
      detected by postoperative left ventriculography. Therefore, DPS may be useful for
      treating LVFWR following AMI.

PMID- 12517303
TI  - Combined bilateral lung resections and off-pump coronary artery bypass grafting.
AB  - We report herein a 74 year old man with angina who had an abnormal chest
      roentgenogram. Computed tomography of the chest showed a solitary 1.0-cm
      peripheral, noncalcified lesion in the apical segment of the left lower lobe and
      a 1.5-cm peripheral lesion in the posterior basal segment of the right lower
      lobe. Coronary angiography revealed the left anterior descending coronary artery
      to have a long 90% stenosis. We report here a case of a combined bilateral lung
      resection and off-pump coronary surgery though a midline sternotomy in a
      compromised lung function patient with both severe coronary artery disease and
      bilateral synchronous primary lung cancer.

PMID- 12517304
TI  - A proteomic approach to the identification of heterogeneous nuclear
      ribonucleoproteins as a new family of poly(ADP-ribose)-binding proteins.
AB  - A new class of poly(ADP-ribose) (pADPr)-binding proteins, heterogeneous nuclear
      ribonucleoproteins (hnRNPs), has been identified by a proteomic approach using
      matrix-assisted laser-desorption-ionization time-of-flight ('MALDI-TOF') MS.
      Liquid-phase isoelectric focusing with a Rotofor cell (Bio-Rad) allowed pre
      fractionation of proteins extracted from HeLa cells. Rotofor protein fractions
      were further separated by SDS/PAGE and then transferred to a PVDF membrane. pADPr
      binding proteins were analysed by autoradiography of the protein blot after
      incubation with (32)P-labelled automodified pADPr polymerase-1 (PARP-1). Peptide
      mass fingerprinting of selected bands identified the most abundant pADPr-binding
      proteins as hnRNPs, a family of proteins that bind pre-mRNA into functional
      complexes involved in mRNA maturation and transport to the cytoplasm. Sequence
      homology database searching against a previously reported pADPr-binding sequence
      motif revealed that the hnRNPs contain a putative pADPr-binding sequence pattern
      [Pleschke, Kleczkowska, Strohm and Althaus (2000) J. Biol. Chem. 275, 40974
      40980]. pADPr-binding assays performed with synthetic peptides by the dot-blot
      technique and with nitrocellulose-transferred recombinant hnRNPs confirmed the
      pADPr-binding protein identification and the specificity of the interaction.
      These results could establish a link between increased levels of pADPr in DNA
      damaged cells and the modified protein expression pattern resulting from altered
      mRNA trafficking.

PMID- 12517305
TI  - Overweight and obesity in relation to cardiovascular disease risk factors among
      medical students in Crete, Greece.
AB  - BACKGROUND: Recent data indicate increasing rates of adult obesity and mortality
      from cardiovascular disease (CVD) in Greece. No data, however, are available on
      prevalence of overweight and obesity in relation to CVD risk factors among young
      adults in Greece. METHODS: A total of 989 third-year medical students (527 men,
      462 women), aged 22 +/- 2 years, were recruited from the University of Crete
      during the period 1989-2001. Anthropometric measures and blood chemistries were
      obtained. The relationships between obesity indices (body mass index [BMI], waist
      circumference [WC], waist-to-hip ratio [WHpR], waist-to-height ratio [WHtR]) and
      CVD risk factor variables (blood pressure, glucose, serum lipoproteins) were
      investigated. RESULTS: Approximately 40% of men and 23% of women had BMI > or =
      25.0 kg/m2. Central obesity was found in 33.4% (average percentage corresponding
      to WC > or = 90 cm, WHpR > or = 0.9 and WHtR > or = 50.0) of male and 21.7%
      (using WC > or = 80 cm, WHpR > or = 0.8, WHtR > or = 50.0) of female students.
      Subjects above the obesity indices cut-offs had significantly higher values of
      CVD risk factor variables. BMI was the strongest predictor of hypertension. WHtR
      in men and WC in women were the most important indicators of dyslipidaemia.
      CONCLUSION: A substantial proportion of Greek medical students were overweight or
      obese, obesity status being related to the presence of hypertension and
      dyslipidaemia. Simple anthropometric indices can be used to identify these CVD
      risk factors. Our results underscore the need to implement health promotion
      programmes and perform large-scale epidemiological studies within the general
      Greek young adult population.

PMID- 12517307
TI  - Romanow, Romanow, wherefore art thou Romanow?

PMID- 12517306
TI  - Expression pattern of a nuclear encoded mitochondrial arginine-ornithine
      translocator gene from Arabidopsis.
AB  - BACKGROUND: Arginine and citrulline serve as nitrogen storage forms, but are also
      involved in biosynthetic and catabolic pathways. Metabolism of arginine,
      citrulline and ornithine is distributed between mitochondria and cytosol. For the
      shuttle of intermediates between cytosol and mitochondria transporters present on
      the inner mitochondrial membrane are required. Yeast contains a mitochondrial
      translocator for ornithine and arginine, Ort1p/Arg11p. Ort1p/Arg11p is a member
      of the mitochondrial carrier family (MCF) essential for ornithine export from
      mitochondria. The yeast arg11 mutant, which is deficient in Ort1p/Arg11p grows
      poorly on media lacking arginine. RESULTS: High-level expression of a nuclear
      encoded Arabidopsis thaliana homolog (AtmBAC2) of Ort1p/Arg11p was able to
      suppress the growth deficiency of arg11. RT-PCR analysis demonstrated expression
      of AtmBAC2 in all tissues with highest levels in flowers. Promoter-GUS fusions
      showed preferential expression in flowers, i.e. pollen, in the vasculature of
      siliques and in aborted seeds. Variable expression was observed in leaf
      vasculature. Induction of the promoter was not observed during the first two
      weeks in seedlings grown on media containing NH4NO3, arginine or ornithine as
      sole nitrogen sources. CONCLUSION: AtmBAC2 was isolated as a mitochondrial
      transporter for arginine in Arabidopsis. The absence of expression in developing
      seeds and in cotyledons of seedlings indicates that other transporters are
      responsible for storage and mobilization of arginine in seeds.

PMID- 12517308
TI  - Point: urologists should take an active role in the diagnosis and treatment of
      hypogonadism in the aging male.
AB  - Andropause is a problem that can be identified in some men as distinct from the
      changes associated with aging or chronic disease. These men have mild
      hypogonadism and a clinical picture that is well within the scope of urologists
      to identify and manage. Andropause is neither life threatening nor trivial and
      there are clinical guidelines published that will help to refine the
      understanding and definition of this condition. The character of andropause is
      distinct from profound hypogonadism in its relation to age, the scope and degree
      of contributing symptoms and the marginal reduction in testosterone. Testosterone
      is the established treatment for some men with andropause and the links between
      testosterone and cancer of the prostate create an overlap in management that
      places a premium on urological expertise. Obviously men with cancer of the
      prostate must not be given testosterone and some men may have clinical andropause
      and undetected cancer of the prostate. However, current understanding points to
      the fact that there is no additional risk from re-establishing a normal androgen
      environment (androgen replacement) in terms of initiating a new cancer of the
      prostate while testosterone will encourage growth of an established cancer.
      Therefore, the natural good practice of urology, and only urology, intrinsically
      encompasses the major issues inherent in the medical collision of cancer of the
      prostate and testosterone replacement. The good practice of urology includes the
      use of androgen replacement therapy in men who need it and have been assessed for
      the presence of cancer of the prostate.

PMID- 12517309
TI  - Counterpoint: urologists should take an active role in the diagnosis and
      treatment of hypogonadism in the aging male.
AB  - The recent interest in the potential applications of new testosterone
      preparations has stimulated industry and physicians to develop indications for
      their use. Despite little scientific evidence to support the widespread
      application of testosterone in aging men, a clinical symptom complex called
      Partial Androgen Deficiency in the Aging Male (PADAM) has been described. Many of
      these symptoms can be successfully treated without testosterone administration.
      The author suggests that prospective randomized clinical trials are necessary to
      support the application of testosterone in the PADAM patient and until then
      physicians take a more balanced approach in this patient population.

PMID- 12517310
TI  - Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol.
AB  - INTRODUCTION/OBJECTIVES: PC-SPES is an herbal mixture available over the counter
      for the treatment of prostate cancer. It was re-called in January 2002 due to
      alleged contamination with warfarin. Other laboratories, including our own, claim
      that the potent synthetic estrogen, diethylstilbestrol (DES) which has been used
      for many years to treat hormone dependent prostate cancer, could be detected in
      the herbal mixture. Recent clinical studies report objective responses in men
      with hormone dependent and naive prostate cancer, and also describe isolated
      cases of estrogenic side effects. A lack of effective conventional treatments for
      advanced hormone refractory prostate cancer has led to a widespread use of PC
      SPES by patients across the North America continent. The presence of DES in PC
      SPES might explain both clinical response and observed side effects in men taking
      6-9 capsules per day. METHODS: We tested five batches of commercially available
      PC-SPES using gas chromatography (GC) and high performance liquid chromatography
      (HPLC) upon methanolic extraction. Duplicate aliquots were tested for each batch
      and the results compared to standard curves generated using DES (99% purity).
      RESULTS AND CONCLUSIONS: We detected significant levels of DES in three out of
      five tested batches. The presence of a synthetic steroid in PC-SPES is not likely
      to have occurred as a result of its extraction from a herbal source. The
      implications of this finding highlight the necessity of regulated quality control
      and standardization of natural health products.

PMID- 12517312
TI  - MCDK not excluded by virtue of function on renal scan.
AB  - INTRODUCTION: The conservative management of multicystic dysplastic kidneys
      (MCDK) has been very successful, largely due to advances in diagnostic imaging.
      Classically, MCDK is described as a non-functioning cystic renal mass. However,
      we noticed that the increasing sensitivity of renal scans is able to demonstrate
      function in MCDK that previously would not have been detected. METHODS: We
      describe eight cases of MCDK with elements of function on renal scan, and their
      follow up. RESULTS AND CONCLUSIONS: One half (4/8) of these children underwent
      nephrectomy, and histology was consistent with MCDK. The remaining 4/8 were
      successfully followed to radiographic involution, without any complications.
      Therefore, we believe that minimal function on nuclear scintigraphy does not
      preclude the diagnosis of MCDK, and is yet another adjustment in our
      understanding of this entity.

PMID- 12517313
TI  - Primary low-grade B-cell lymphoma of the urinary bladder: case report and
      literature review.
AB  - The first recorded case of lymphoma of the bladder was reported by Eve and
      Chaffey in 1885. Malignant lymphoma of the bladder can be classified into one of
      three different clinical groups: 1) Primary lymphoma localized to the bladder; 2)
      Lymphoma presenting in the bladder as the first sign of disseminated disease (non
      localized lymphoma); 3) Recurrent bladder involvement by lymphoma in patients
      with a history of malignant lymphoma (secondary lymphoma). Primary extranodal
      marginal zone lymphoma of mucosa associated lymphoid tissue (MALT type) of the
      urinary bladder, first described by Kempton et al in 1990, is the most common
      primary bladder lymphoma and associated with an excellent prognosis. We present a
      patient with gross hematuria who was found to have a primary bladder lymphoma and
      review the relevant literature.

PMID- 12517314
TI  - Segmental testicular infarction: diagnosis and strategy.
AB  - OBJECTIVES: We report the usefulness of ultrasonography and magnetic resonance
      imaging (MRI) findings in testicular infarction, in order to avoid surgical
      exploration. METHODS: In December 2000, a 37-year-old African male presented with
      left testicular pain and no prior history of trauma. Physical examination,
      ultrasonography and MRI were performed by an experienced radiologist (D.T.),
      which suggested a segmental testicular infarction. Surgical exploration was not
      performed and a period of watchful waiting with evolution control by
      ultrasonography was decided. RESULTS: After a 3 month follow-up, the
      ultrasonography control revealed a total re-vascularization of the vessels and a
      reduction of the lesion size. CONCLUSION: The authors suggest that the
      combination of ultrasonography and MRI, in the management of testicular
      infarction, may avoid invasive surgery.

PMID- 12517315
TI  - Renal colic and torsion: case report and review.
AB  - Acute ureteric colic and acute scrotum are among the most commonly seen
      urological emergencies. We present a case in which a male patient presented with
      simultaneous right flank pain and ipsilateral scrotal pain.

PMID- 12517316
TI  - A case of spontaneous perirenal hemorrhage secondary to polyarteritis nodosa.
AB  - A case report of a patient who develops a spontaneous perinephric hemorrhage
      secondary to polyarteritis nodosa (PAN) is described. The diagnosis of PAN was
      delayed in this patient somewhat due to a previously unrecognized relation to a
      recent perihepatic hemorrhage. Unenhanced CT findings in this case were
      nonspecific, but follow up angiography demonstrated characteristic subsegmental
      and interlobular renal artery aneurysms. Spontaneous perinephric hemorrhage is an
      uncommon complication of PAN however an elevated level of suspicion regarding the
      diagnosis of a systemic vasculitis should be considered in any case of
      spontaneous renal, hepatic, or gastrointestinal hemorrhage.

PMID- 12517317
TI  - Reply to editorial -- Technologies and traditional skills, Laurence H. Klotz, Can
      J Urol 2002;9(4):1572-1573.

PMID- 12517318
TI  - Do you know? 

PMID- 12517319
TI  - The population health perspective as a framework for studying child maltreatment
      outcomes.
AB  - The population health perspective (PHP) is commonly used in addressing a wide
      range of health issues. This article examines the strengths and limitations of
      the perspective. The determinants of health that are an integral part of the PHP
      are used as a framework in considering the range of outcomes associated with
      exposure to child maltreatment. Directions for further research are outlined.

PMID- 12517320
TI  - Perceptions of disease severity and barriers to self-care predict glycemic
      control in Aboriginal persons with type 2 diabetes mellitus.
AB  - The Health Belief Model (HBM) was evaluated for secondary prevention of type 2
      diabetes mellitus in an Aboriginal population in British Columbia. Glycemic
      markers (glycated hemoglobin [HbA1c]), insulin and post-load glucose), diabetes
      health beliefs (susceptibility, severity, benefits and barriers), knowledge and
      behaviour were measured for 16 men and 18 women with diabetes (age [SD]=57.7
      [11.6]). Eighteen months later, HbA1c and behaviour were measured for all
      participants, and health beliefs obtained for 17 of them. Perceived severity and
      perceived barriers were related to glycemic status at baseline and follow up, and
      predicted reduction in HbA1c (b[SE]   |0.40| [0.18], p <0.05). The results
      support a therapeutic emphasis on belief in the severity of diabetes
      complications, and the complementary belief that barriers to therapeutic
      behaviour can be overcome in efforts to support Aboriginal persons with diabetes
      to manage their disease. The empirical utility of the HBM in glycemic control was
      partially upheld.

PMID- 12517321
TI  - Do hospital E-codes consistently capture suicidal behaviour?
AB  - Hospital separation data are used to study suicidal behaviour; however, there is
      little information about the appropriateness of these data for research and
      planning activities. The study purpose is to examine how consistently hospital
      separation E-code data reflect suicidal behaviours. Expert clinicians reviewed
      medical records of individuals who had a separation for self-poisoning to
      determine whether the self-poisoning was deliberate. Agreement among clinicians
      was evaluated and latent class analysis performed to derive a summary estimate of
      the prevalence of deliberate self-poisoning. This estimate was then compared to
      the prevalence of deliberate self-poisoning based on the external cause of injury
      (E-codes). Clinicians estimated the prevalence to be 63% higher than the E-code
      based prevalence. Much larger discrepancies were apparent among older age groups,
      those whose care was primarily medical in nature and those with a longer length
      of hospital stay. In acute care settings, self-poisonings among the elderly may
      not receive adequate attention and/or documentation. Estimating the prevalence of
      admissions for suicidal behaviour using hospital separation data is of
      questionable validity, particularly among older age groups.

PMID- 12517322
TI  - The impact of missing birth weight in deceased versus surviving fetuses and
      infants in the comparison of birth weight-specific feto-infant mortality.
AB  - Birth weight-specific is preferred to crude feto-infant mortality in
      epidemiologic studies comparing rates across jurisdictions, because it can help
      limit the bias arising from regional differences in the completeness of reporting
      of vital events and in classification of live versus stillbirth among extremely
      small and immature infants. The potential impact of missing birth weight
      information in deceased versus surviving fetuses and infants in the comparison of
      birth weight-specific feto-infant mortality has been seldom examined, however.
      The authors investigated this issue, using data collected from two nationwide
      surveys of all pregnancy outcomes occurring 15 17 May 1989 and 12 16 February
      1996, respectively, in Taiwan and the 1989 and 1996 linked birth and infant death
      records in Canada (excluding Ontario and Newfoundland). The proportions with
      missing birth weight information in Taiwan in 1989 were 25.0%, 15.4%, 0%, and
      0.6%, respectively, for stillbirths, neonatal deaths, post-neonatal deaths, and
      survivors, and in 1996 were 100%, 5.0%, 0%, and 0.2%. The proportions with
      missing birth weight information in Canada in 1989 were 5.8%, 2.6%, 1.2%, and
      0.6%, respectively, for fetal deaths, neonatal deaths, post-neonatal deaths, and
      survivors, and in 1996 were 5.0%, 2.4%, 1.1%, and 0.6%. Infant and (especially)
      fetal death rates were substantially higher in Taiwan than in Canada among births
      with missing birth weight. The authors concluded that differences in missing
      birth weight information between deaths and survivors can bias comparisons of
      birth weight-specific feto-infant mortality.

PMID- 12517323
TI  - Cancer Care Ontario's New Drug Funding Program: controlled introduction of
      expensive anticancer drugs.
AB  - In the mid 1990s, the high cost and increasing number of new anticancer and
      supportive care drugs began to result in an inequality of access to promising new
      treatment approaches in the Province of Ontario. Starting with a single drug,
      paclitaxel, in 1995, the New Drug Funding Program has evolved to a provincial
      program that enables cancer patients in Canada's most populous province to
      equitably access new and expensive, intravenously administered drugs. This
      article describes the development of the program, including the evolution of the
      administrative mechanisms necessary to manage the program and the decisions of
      the Policy Advisory Committee that shape provincial funding policies. In fiscal
      year 2000/2001, the Program made 14 drugs available for 24 indications for a
      total provincial expenditure of approximately $37.7 million. These intravenous
      drugs can now be accessed through nine Regional Cancer Centres, the province's
      only cancer hospital (Princess Margaret Hospital) and 80 community hospitals and
      will directly benefit more than 8,700 patients.

PMID- 12517325
TI  - Functional characteristics of chorionic plate placental arteries from normal
      pregnant women and women with pre-eclampsia.
AB  - OBJECTIVES: We aimed to compare placental small artery function from women with
      pre-eclampsia and normal pregnancy. In particular, we wished to test the
      hypothesis that these arteries respond differently to an endothelium-dependent
      vasodilator, to the presence of nitric oxide, and to the presence of cyclic
      monophosphate nucleotides. METHODS: A small vessel wire myograph was used to
      study placental arteries (200 to 550 microm). Contractile function was assessed
      with vasopressin. Relaxation was assessed with the endothelium-dependent
      vasodilator, bradykinin, and the endothelium-independent vasodilators sodium
      nitroprusside (a nitric oxide donor) and papaverine (a phosphodiesterase
      inhibitor). RESULTS: The constrictor response to vasopressin did not differ
      between patient groups (p=0.79; repeated measures ANOVA). For both normal
      pregnancy and pre-eclampsia, the response of pre-constricted arteries to the
      endothelium-dependent vasodilator, bradykinin, was minimal. Vasorelaxation to
      sodium nitroprusside and papaverine was attenuated in pre-eclampsia compared to
      normal pregnancy (p=0.03 and p<0.001, respectively; repeated measures ANOVA).
      CONCLUSIONS: In pre-eclampsia, placental arteries exhibit an attenuated
      vasodilatory response to nitric oxide.

PMID- 12517326
TI  - Labetalol decreases cerebral perfusion pressure without negatively affecting
      cerebral blood flow in hypertensive gravidas.
AB  - OBJECTIVE: To research the cerebral hemodynamic effects of labetalol in pregnant
      women with hypertension. DESIGN: Prospective observational study. SETTING:
      Tertiary Care Medical Center. POPULATION: Pregnant patients with hypertension.
      METHODS: Transcranial Doppler (TCD) ultrasound was used to measure the blood
      velocity in the middle cerebral arteries (MCA) of eight pregnant patients with
      hypertension, before and after the administration of a 200 mg oral dose of
      labetalol. Five patients had severe preeclampsia, and three had chronic
      hypertension with superimposed preeclampsia. MCA blood velocity and systemic
      blood pressure were measured simultaneously at the baseline, and at 60 and 180
      min after labetalol. Selected cerebral hemodynamic parameters were compared with
      normative curves. Values outside of the 5th and 95th percentiles were regarded as
      abnormal. MAIN OUTCOME MEASURES: Cerebral perfusion pressure (CPP), resistance
      area product (RAP), and cerebral flow index (CFI). RESULTS: Patient age,
      gestational age, and parity were similar to those of the normal women from whom
      the normative data were obtained. Women with hypertension had higher baseline
      CPP, MAP, and RAP than normal pregnant women, but their CFI was within the normal
      range. Labetalol reduced the CPP, as well as the systolic, diastolic, and mean BP
      significantly at 60 and 180 min without significantly affecting the heart rate,
      MCA velocities, RAP, or CFI. CONCLUSIONS: Labetalol effectively reduces CPP,
      without affecting cerebral perfusion, primarily by a decrease in systemic blood
      pressure. This makes it an ideal agent for blood pressure control in severely
      hypertensive pregnant women.

PMID- 12517327
TI  - Concentrations of apolipoproteins E, C2, and C3 and lipid profile in
      preeclampsia.
AB  - OBJECTIVE: Preeclampsia is associated with an abnormal lipid profile and high
      apolipoprotein E (Apo E) levels. Apo E may favor lipid uptake by macrophages and
      is thought to increase triglycerides clearance. However, high Apo E levels may
      interfere with lipolysis by interacting with the lipoprotein lipase (LPL)
      activator, apolipoprotein C2 (Apo C2). LPL activity may also be impaired by high
      levels of the LPL inhibitor apolipoprotein C3 (Apo C3). Therefore, lipid profile
      depends on the balance between the opposing effects of Apo C2 and Apo C3 and on
      interference due to Apo E. We investigated the involvement of these three
      lipoproteins in lipid disorders associated with preeclampsia. METHODS: Blood
      samples were taken from 25 normotensive and 24 preeclamptic pregnant women after
      a 12-hr fasting period. These samples were analyzed for standard lipid profile
      and Apo E, C2, C3 concentrations. RESULTS: Concentrations of triglycerides, total
      cholesterol, LDL, HDL, and LDL cholesterol did not differ significantly between
      preeclamptic women and pregnant controls. Apo C2 concentration and Apo E/Apo C2
      ratio did not differ between the two groups of women but Apo C3 and Apo E
      concentrations were higher in preeclamptic than in pregnant controls. The ratio
      of triglycerides to Apo E was similar in the two groups of women. In both groups,
      triglycerides levels were positively correlated with Apo E (p=0.0429), Apo C2
      (p=0.0045) and Apo C3 (p=0.0004) concentrations, but not with Apo E/Apo C2 ratio
      (p=0.760). CONCLUSIONS: In preeclamptic women, the increase in Apo E
      concentration may not increase triglycerides clearance because LPL activity seems
      to be inhibited by high Apo C3 concentration.

PMID- 12517328
TI  - Oxidative stress reproduces placental abnormalities of preeclampsia.
AB  - OBJECTIVE: The activities of placental superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px), but not catalase, are lower than normal in preeclampsia,
      which could contribute to the uncontrolled placental production of lipid
      peroxides and thromboxane (TX). Oxidative stress, hyperlipidemia and increased
      iron levels in the maternal compartment in preeclampsia could be responsible for
      these placental changes by causing oxidative stress in the placenta. METHODS: We
      tested this possibility in vitro by exposing a trophoblast-like cell line, ED27,
      to a combination of linoleic acid (LA, 90 microM) and an oxidizing solution
      composed of hypoxanthine, xanthine oxidase and ferrous sulfate (OxLA) for 6 days.
      For these studies, the cells were treated with dexamethasone (10-8 M) for the
      first 72 hr. This was done to differentiate the cells into a phenotype more like
      syncytiotrophoblast cells as evidenced by production of beta-human chorionic
      gonadotropin (beta-hCG). RESULTS: After 6 days of exposure to OxLA, the
      activities of SOD and GSH-Px were significantly decreased as compared to exposure
      to LA alone. In contrast, catalase activity was increased by OxLA. The OxLA
      induced decreases in SOD and GSH-Px activities were attenuated by deferoxamine,
      an iron chelator, suggesting a role for Fe2+ in the decreased activities.
      Compared to LA, OxLA significantly increased TX secretion and lipid peroxidation
      in cells and media at 2, 4 and 6 days. Deferoxamine inhibited the OxLA-induced
      increase in lipid peroxidation, but not the increase in TX. Isolation of
      trophoblast cells and villous core tissue from term placentas verified that
      antioxidant enzyme activity was localized primarily to the trophoblast cell
      compartment lending validity to the in vitro findings. CONCLUSIONS: These data
      mimic the changes in placental SOD, GSH-Px, catalase, TX and lipid peroxidation
      that occur in preeclampsia suggesting that maternal hyperlipidemia and increased
      iron levels may be responsible for placental oxidative stress and abnormalities
      in antioxidants and thromboxane.

PMID- 12517329
TI  - Comparison of the efficacy of continuous furosemide and low-dose dopamine
      infusion in preeclampsia/eclampsia-related oliguria in the immediate postpartum
      period.
AB  - AIM: To compare the efficacy of furosemide infusion with that of low-dose
      dopamine infusion in improving urine output and subsequent renal function in
      preeclamptic/eclamptic patients with oliguria in the immediate postpartum period.
      DESIGN: Prospective randomised single blind clinical trial. SETTING: Obstetric
      High Care Unit of King Edward VIII Hospital, a large referral tertiary hospital.
      METHOD: Eighty postpartum patients with severe preeclampsia/eclampsia with
      oliguria were enrolled. Hypovolaemia was corrected under central venous pressure
      (CVP) monitoring and urine output monitored for 4 hr. Patients who remained
      oliguric were randomly assigned to a continuous infusion of low-dose dopamine (3
      microg/kg/min), or furosemide 5 mg/hr infusion, for 12 hr. In patients with no
      response after 12 hr, the drugs were switched and continued for a further 12 hr.
      A subgroup of patients who responded 4 hr after correction of hypovolaemia was
      observed for 12 hr. The primary outcome measured involved the comparison in urine
      output between the different drug regimes and the number of patients requiring
      haemodialysis. Secondary outcome measures involved assessment of serum urea and
      creatinine values in the two treatment groups. RESULTS: Of the 80 patients
      enrolled, 20 improved their urine outputs within the 4-hr observation period.
      Sixty patients were randomised to furosemide or low-dose dopamine infusion. There
      was no statistical significant difference in the mean hourly urine output, rate
      of change in urine output over time and the mean urea or creatinine levels
      between the treatment groups. Ten percent of patients that failed on furosemide
      primarily, and 8.5% of patients that failed on initial low-dose dopamine,
      received haemodialysis. The difference in demographic and clinic data between
      these groups was not statistically significant. CONCLUSION: Administration of
      continuous infusion of furosemide showed comparable efficacy to low-dose dopamine
      infusion in ameliorating oliguria in severe preeclampsia/eclampsia post delivery;
      there was no difference in the percentage of patients that required haemodialysis
      in either group.

PMID- 12517330
TI  - Basic fibroblast growth factor and hypertensive disorders in pregnancy.
AB  - OBJECTIVE: We examined serum concentrations of basic fibroblast growth factor
      (bFGF) in women with hypertensive disorders in pregnancy and analyzed whether
      serum concentrations of bFGF can be used as a discriminator between mild and
      severe preeclampsia. METHODS: One hundred and twenty pregnant women were included
      in this prospective cohort study. We evaluated serum concentrations of bFGF in
      pregnant women with chronic hypertension (n=22), mild preeclampsia (n=40), severe
      preeclampsia (n=31), and healthy pregnant women (n=27). RESULTS: Median serum
      concentrations of bFGF in healthy pregnant women, women with chronic
      hypertension, and women with mild or severe preeclampsia were 0.0 (0-37.2), 0.0
      (0-3.0), 1.7 (0-97.2), and 0.0 (0-52.0), respectively. Comparison of the median
      values of serum bFGF concentrations showed a significant difference between
      healthy pregnant women and women with mild preeclampsia (P=0.02). In a logistic
      regression model, we found a significant influence of bFGF serum concentrations
      on the diagnosis of mild preeclampsia (P=0.01), but not on the diagnosis of
      chronic hypertension (P=0.19) or severe preeclampsia (P=0.41). CONCLUSIONS:
      Elevated serum concentrations of bFGF are associated with mild preeclampsia, but
      are not discriminatory for the distinction between mild and severe preeclampsia.

PMID- 12517331
TI  - Hold tight (but not too tight) to get it right: accurate bypass of an 8
      oxoguanine lesion by DNA polymerase beta.
AB  - Crystal structures of DNA polymerase beta encountering an 8-oxoguanine lesion
      show how the polymerase selects an otherwise unfavorable conformation of a
      damaged template base to enable error-free bypass.

PMID- 12517332
TI  - Regulating UBP-mediated ubiquitin deconjugation.
AB  - The first crystal structures have been obtained for a UBP domain both alone and
      in complex with ubiquitin aldehyde, thus providing a framework for structural
      conservation throughout the UBP protease family. Comparison of the structures
      provides substantial insight into ubiquitin-mediated activation of UBP protease
      activity, a process that potentially regulates substrate-dependent ubiquitin
      deconjugation.

PMID- 12517333
TI  - A closer look of the HECTic ubiquitin ligases.
AB  - In comparison with previous studies, a new crystal structure of a HECT ubiquitin
      ligase catalytic domain has revealed the structural basis of the conformational
      flexibility of the enzyme and provides insights into the mechanism underlying the
      ubiquitin transfer reaction in the polyubiquitination pathway.

PMID- 12517334
TI  - Twenty thousand ORFan microbial protein families for the biologist?
AB  - The genomes of most newly sequenced organisms contain a significant fraction of
      ORFs (open reading frames) that match no other sequence in the databases. We
      refer to these singleton ORFs as sequence ORFans. Because little can be learned
      about ORFans by homology, the origin and functions of ORFans remain a mystery.
      However, in this era of full genome sequencing, it seems that ORFans have been
      underemphasized. In this minireview, we draw attention to the increasing number
      of ORFans and to the consequences of this growth to biological research in the
      postgenomic era.

PMID- 12517335
TI  - Depositing electron microscopy maps.
AB  - A meeting was held at the European Bioinformatics Institute (EBI) in Hinxton,
      United Kingdom to discuss recent progress in the development of EMD, a database
      for maps determined by electron microscopy that is now integrated with MSD, the
      macromolecular structure database at EBI. This meeting of representatives of many
      of the major image processing groups in electron microscopy also discussed
      possible software developments that would ease the documentation and deposition
      of such datasets. The meeting concluded with a strong endorsement of map
      deposition in electron microscopy and its linkage with the family of archival
      databases in biomedical research.

PMID- 12517336
TI  - How does radiation damage in protein crystals depend on X-ray dose?
AB  - Is radiation damage to cryopreserved protein crystals strictly proportional to
      accumulated dose at the high-flux density of beams from undulators at third
      generation synchrotron sources? The answer is "yes," for overall damage to
      several different kinds of protein crystals at flux densities up to 10(15)
      ph/sec/mm(2) (APS beamline 19-ID). We find that, at 12 keV (1 A wavelength),
      about ten absorbed photons are sufficient to "kill" a unit cell. As this
      corresponds to about one elastically scattered photon, each unit cell can
      contribute only about one photon to total Bragg diffraction. The smallest crystal
      that can yield a full data set to 3.5 A resolution has a diameter of about 20
      microm (100 A unit cell).

PMID- 12517337
TI  - Crystal structure of an inactive Akt2 kinase domain.
AB  - Akt/PKB represents a subfamily of three isoforms from the AGC serine/threonine
      kinase family. Amplification of Akt activity has been implicated in diseases that
      involve inappropriate cell survival, including a number of human malignancies.
      The structure of an inactive and unliganded Akt2 kinase domain reveals several
      features that distinguish it from other kinases. Most of the alpha helix C is
      disordered. The activation loop in this structure adopts a conformation that
      appears to sterically hinder the binding of both ATP and peptide substrate. In
      addition, an intramolecular disulfide bond is observed between two cysteines in
      the activation loop. Residues within the linker region between the N- and C
      terminal lobes also contribute to the inactive conformation by partially
      occupying the ATP binding site.

PMID- 12517338
TI  - Structure of Escherichia coli ribose-5-phosphate isomerase: a ubiquitous enzyme
      of the pentose phosphate pathway and the Calvin cycle.
AB  - Ribose-5-phosphate isomerase A (RpiA; EC 5.3.1.6) interconverts ribose-5
      phosphate and ribulose-5-phosphate. This enzyme plays essential roles in
      carbohydrate anabolism and catabolism; it is ubiquitous and highly conserved. The
      structure of RpiA from Escherichia coli was solved by multiwavelength anomalous
      diffraction (MAD) phasing, and refined to 1.5 A resolution (R factor 22.4%,
      R(free) 23.7%). RpiA exhibits an alpha/beta/(alpha/beta)/beta/alpha fold, some
      portions of which are similar to proteins of the alcohol dehydrogenase family.
      The two subunits of the dimer in the asymmetric unit have different
      conformations, representing the opening/closing of a cleft. Active site residues
      were identified in the cleft using sequence conservation, as well as the
      structure of a complex with the inhibitor arabinose-5-phosphate at 1.25 A
      resolution. A mechanism for acid-base catalysis is proposed.

PMID- 12517339
TI  - Comparison of X-ray crystal structure of the 30S subunit-antibiotic complex with
      NMR structure of decoding site oligonucleotide-paromomycin complex.
AB  - Aminoglycoside antibiotics that bind to 16S ribosomal RNA in the aminoacyl-tRNA
      site (A site) cause misreading of the genetic code and inhibit translocation.
      Structures of an A site RNA oligonucleotide free in solution and bound to the
      aminoglycosides paromomycin or gentamicin C1a have been determined by NMR.
      Recently, the X-ray crystal structure of the entire 30S subunit has been
      determined, free and bound to paromomycin. Distinct differences were observed in
      the crystal structure, particularly at A1493. Here, the NMR structure of the
      oligonucleotide-paromomycin complex was determined with higher precision and is
      compared with the X-ray crystal structure of the 30S subunit complex. The
      comparison shows the validity of both structures in identifying critical
      interactions that affect ribosome function.

PMID- 12517340
TI  - The crystal structure of a cyanobacterial water-soluble carotenoid binding
      protein.
AB  - Carotenoids undergo a wide range of photochemical reactions in animal, plant, and
      microbial systems. In photosynthetic organisms, in addition to light harvesting,
      they perform an essential role in protecting against light-induced damage by
      quenching singlet oxygen, superoxide anion radicals, or triplet-state
      chlorophyll. We have determined the crystal structure of a water-soluble orange
      carotenoid protein (OCP) isolated from the cyanobacterium Arthrospira maxima at a
      resolution of 2.1 A. OCP forms a homodimer with one carotenoid molecule per
      monomer. The carotenoid binding site is lined by a striking number of methionine
      residues. The structure reveals several possible ways in which the protein
      environment influences the spectral properties of the pigment and provides
      insight into how the OCP carries out its putative functions in photoprotection.

PMID- 12517341
TI  - Sequential unfolding of ankyrin repeats in tumor suppressor p16.
AB  - The ANK repeat is a ubiquitous 33-residue motif that adopts a beta hairpin helix
      loop-helix fold. Multiple tandem repeats stack in a linear manner to produce an
      elongated structure that is stabilized predominantly by short-range interactions
      between residues close in sequence. The tumor suppressor p16(INK4) consists of
      four repeats and represents the minimal ANK folding unit. We found from Phi value
      analysis that p16 unfolded sequentially. The two N-terminal ANK repeats, which
      are distorted from the canonical ANK structure in all INK4 proteins and which are
      important for functional specificity, were mainly unstructured in the rate
      limiting transition state for folding/unfolding, while the two C-terminal repeats
      were fully formed. A sequential unfolding mechanism could have implications for
      the cellular fate of wild-type and cancer-associated mutant p16 proteins.

PMID- 12517342
TI  - Metal-free and Ca2+-bound structures of a multidomain EF-hand protein, CBP40,
      from the lower eukaryote Physarum polycephalum.
AB  - Acellular slime mold, Physarum polycephalum, has a unique wound-healing system.
      When cytoplasm of plasmodia is exposed to extracellular fluid, calcium binding
      protein 40 (CBP40) seals damaged areas, forming large aggregates Ca(2+)
      dependently. Part of the CBP40 is truncated at the N terminus by a proteinase in
      plasmodia (CBP40delta), which does not aggregate in the Ca(2+)-bound form. Here
      we report the crystal structures of CBP40delta in both the metal-free and the
      Ca(2+)-bound states. Both structures consist of three domains: coiled-coil,
      intervening, and EF-hand. The topology of the EF-hand domain is similar to that
      of calpain. The N-terminal half of CBP40Delta interacts with the C-terminal EF
      hands through a large hydrophobic interface, necessary for high Ca(2+) affinity.
      Conformational change upon Ca(2+) binding is small; however, the structure of
      CBP40delta provides novel insights into the mechanism of Ca(2+)-dependent
      oligomerization.

PMID- 12517344
TI  - Crystal structure of the human neuropilin-1 b1 domain.
AB  - Neuropilin-1 (Npn-1) is a type I cell surface receptor involved in a broad range
      of developmental processes, including axon guidance, angiogenesis, and
      heterophilic cell adhesion. We have determined the crystal structure of the human
      Npn-1 b1 domain to 1.9 A. The overall structure resembles coagulation factor V
      and VIII (F5/8) C1 and C2 domains, exhibiting a distorted jellyroll fold. Details
      of the structure provide insight to b1 domain regions responsible for ligand
      binding and facilitate rationalization of existing biochemical binding data. A
      polar cleft formed by adjacent loops at one end of the molecule in conjunction
      with flanking electronegative surfaces may represent the binding site for the
      positively charged tails of semaphorins and VEGF(165). The nature of the cell
      adhesion binding site of the b1 domain can be visualized in context of the
      structure.

PMID- 12517345
TI  - Structure of glycerol dehydratase reactivase: a new type of molecular chaperone.
AB  - The function of glycerol dehydratase (GDH) reactivase is to remove damaged
      coenzyme B(12) from GDH that has suffered mechanism-based inactivation. The
      structure of GDH reactivase from Klebsiella pneumoniae was determined at 2.4 A
      resolution by the single isomorphous replacement with anomalous signal (SIR/AS)
      method. Each tetramer contains two elongated 63 kDa alpha subunits and two
      globular 14 kDa beta subunits. The alpha subunit contains structural features
      resembling both GroEL and Hsp70 groups of chaperones, and it appears chaperone
      like in its interactions with ATP. The fold of the beta subunit resembles that of
      the beta subunit of glycerol dehydratase, except that it lacks some coenzyme
      B(12) binding elements. A hypothesis for the reactivation mechanism of reactivase
      is proposed based on these structural features.

PMID- 12517343
TI  - Binary structure of the two-domain (3R)-hydroxyacyl-CoA dehydrogenase from rat
      peroxisomal multifunctional enzyme type 2 at 2.38 A resolution.
AB  - The crystal structure of (3R)-hydroxyacyl-CoA dehydrogenase of rat peroxisomal
      multifunctional enzyme type 2 (MFE-2) was solved at 2.38 A resolution. The
      catalytic entity reveals an alpha/beta short chain alcohol
      dehydrogenase/reductase (SDR) fold and the conformation of the bound nicotinamide
      adenine dinucleotide (NAD(+)) found in other SDR enzymes. Of great interest is
      the separate COOH-terminal domain, which is not seen in other SDR structures.
      This domain completes the active site cavity of the neighboring monomer and
      extends dimeric interactions. Peroxisomal diseases that arise because of point
      mutations in the dehydrogenase-coding region of the MFE-2 gene can be mapped to
      changes in amino acids involved in NAD(+) binding and protein dimerization.

PMID- 12517347
TI  - More review content in TICS 2003.

PMID- 12517346
TI  - Structure of DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine
      reveals structural insights into its coding potential.
AB  - Oxidative damage to DNA generates 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG).
      During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or
      adenine. The ability to accurately replicate through this lesion depends on the
      DNA polymerase. We report the first structure of a polymerase with a promutagenic
      DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine
      residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an
      incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the
      templating nucleotide flips 180 degrees. Thus, the flexibility of the template
      sugar-phosphate backbone near the polymerase active site is one parameter that
      influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into
      the mechanisms employed by polymerases to select the complementary dNTP.

PMID- 12517348
TI  - Depth of strategic reasoning in games.
AB  - Orthodox game theory assumes indefinitely recursive reasoning ('I think that you
      think that I think em leader '), but human decision-makers, who are limited by
      bounded rationality, cannot handle limitless layers of complexity. Recent
      research corroborates earlier findings that human players tend to operate at only
      one or two levels of strategic depth.

PMID- 12517349
TI  - Two paradigms for depth of strategic reasoning in games. Response to Colman.
AB  - We contrast two approaches to probing the depth of theory-of-mind (ToM) reasoning
      by adults in matrix game settings: our own and that of Stahl and Wilson.

PMID- 12517350
TI  - Space is special in Sign.
AB  - Following groundbreaking work by linguists and cognitive scientists over the past
      thirty years, it is now generally accepted that sign languages of the deaf, such
      as ASL (American Sign Language) or BSL (British Sign Language), are structured
      and processed in a similar manner to spoken languages. The one striking
      difference is that they operate in a wholly non-auditory, visuospatial medium.
      How does the medium impact on language processing itself?

PMID- 12517351
TI  - Natural scenes upset the visual applecart.
AB  - The effortless ease of everyday vision seems to contradict numerous findings on
      the limited capacity of visual attention. However, natural scenes appear to
      escape the stringent limitations of attention that apply to seemingly far simpler
      stimuli. This astonishing result will oblige us to rethink the nature of visual
      attention and its limited capacity.

PMID- 12517352
TI  - Why do some perceptual illusions affect visually guided action, when others
      don't?

PMID- 12517353
TI  - Why visual attention and awareness are different.
AB  - Now that the study of consciousness is warmly embraced by cognitive scientists,
      much confusion seems to arise between the concepts of visual attention and visual
      awareness. Often, visual awareness is equated to what is in the focus of
      attention. There are, however, two sets of arguments to separate attention from
      awareness: a psychological/theoretical one and a neurobiological one. By
      combining these arguments I present definitions of visual attention and awareness
      that clearly distinguish between the two, yet explain why attention and awareness
      are so intricately related. In fact, there seems more overlap between mechanisms
      of memory and awareness than between those of attention and awareness.

PMID- 12517354
TI  - Simplicity: a unifying principle in cognitive science?
AB  - Much of perception, learning and high-level cognition involves finding patterns
      in data. But there are always infinitely many patterns compatible with any finite
      amount of data. How does the cognitive system choose 'sensible' patterns? A long
      tradition in epistemology, philosophy of science, and mathematical and
      computational theories of learning argues that patterns 'should' be chosen
      according to how simply they explain the data. This article reviews research
      exploring the idea that simplicity drives a wide range of cognitive processes. We
      outline mathematical theory, computational results and empirical data that
      underpin this viewpoint.

PMID- 12517355
TI  - Learning to see faces and objects.
AB  - Visual recognition of objects is an impressively difficult problem that
      biological systems solve effortlessly. We consider two aspects of this ability.
      First, is the recognition of all objects accomplished by either a single system
      or multiple, domain-specific systems? Behavioral, neuropsychological and
      neuroimaging data indicate that a single system is sufficient for the recognition
      of all objects at all levels. Second, how does such a system 'tune' itself to the
      constraints imposed by recognition at different levels of specificity? Evidence
      indicates that the task demands and learning that arise from different forms of
      feedback determine which computational routines are recruited automatically in
      object recognition.

PMID- 12517356
TI  - Evaluating perception in driving simulation experiments.
AB  - The use of driving simulation for vehicle design and driver perception studies is
      expanding rapidly. This is largely because simulation saves engineering time and
      costs, and can be used for studies of road and traffic safety. How applicable
      driving simulation is to the real world is unclear however, because analyses of
      perceptual criteria carried out in driving simulation experiments are
      controversial. On the one hand, recent data suggest that, in driving simulators
      with a large field of view, longitudinal speed can be estimated correctly from
      visual information. On the other hand, recent psychophysical studies have
      revealed an unexpectedly important contribution of vestibular cues in distance
      perception and steering, prompting a re-evaluation of the role of visuo
      vestibular interaction in driving simulation studies.

PMID- 12517357
TI  - Neural correlates of the first-person-perspective.
AB  - Human self-consciousness depends on the metarepresentation of mental and bodily
      states as one's own mental and bodily states. First-person-perspective taking is
      not sufficient, but necessary for human self-consciousness. To assign a first
      person-perspective is to center one's own multimodal experiential space upon
      one's own body, thus operating in an egocentric reference frame. The brain
      regions involved in assigning first-person-perspective comprise medial
      prefrontal, medial parietal and lateral temporoparietal cortex. These empirical
      findings complement recent neurobiologically oriented theories of self
      consciousness which focus on the relation between the subject and his/her
      environment by supplying a neural basis for its key components.

PMID- 12517358
TI  - Learning, prediction and causal Bayes nets.
AB  - Recent research in cognitive and developmental psychology on acquiring and using
      causal knowledge uses the causal Bayes net formalism, which simultaneously
      represents hypotheses about causal relations, probability relations, and effects
      of interventions. The formalism provides new normative standards for
      reinterpreting experiments on human judgment, offers a precise interpretation of
      mechanisms, and allows generalizations of existing theories of causal learning.
      Combined with hypotheses about learning algorithms, the formalism makes
      predictions about inferences in many experimental designs beyond the classical,
      Pavlovian cue-->effect design.

PMID- 12517359
TI  - Inhaled beta-2 adrenergic receptor agonists and primary cardiac arrest.
AB  - PURPOSE: We sought to investigate if short-acting, inhaled beta2-adrenergic
      receptor agonists were associated with higher risk of primary cardiac arrest in
      patients with asthma or chronic obstructive pulmonary disease (COPD). SUBJECTS
      AND METHODS: We conducted a population-based study involving 454 patients
      enrolled in a health maintenance organization, aged 40 to 79 years, who had
      asthma or COPD and who experienced primary cardiac arrest during 1980 to 1994. We
      randomly selected 586 controls from strata of enrollees, defined by age, sex,
      calendar year, and prior heart disease. Medication use was assessed from
      computerized pharmacy data, and risk factors from medical record review. RESULTS:
      Use of inhaled beta-agonists was associated with a twofold increased risk of
      primary cardiac arrest (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.1
      to 3.3) among patients with asthma, but not among those with COPD (OR = 1.3; 95%
      CI: 0.6 to 2.7), after adjustment for risk factors. This association was observed
      only with use of two or more canisters of metered-dose, inhaled beta-agonists for
      3 months, and when inhaled steroids were not used. CONCLUSION: These results
      support current guidelines recommending inhaled steroids as first-line asthma
      therapy.

PMID- 12517360
TI  - Use of cytosolic and myofibril markers in the detection of ongoing myocardial
      damage in patients with chronic heart failure.
AB  - PURPOSE: Measurement of serum levels of cytosolic and myofibril components of
      cardiac tissue could indicate ongoing myocardial damage in patients with chronic
      heart failure. METHODS: We correlated serum levels of a cytosolic marker (heart
      type fatty acid-binding protein) and a myofibril marker (troponin T) with the
      severity of symptoms (based on the New York Heart Association [NYHA] class),
      neurohumoral derangement, and subsequent cardiac events in 56 patients with
      chronic heart failure. RESULTS: Mean (+/- SD) levels of heart-type fatty acid
      binding protein were greater in patients with NYHA class III or IV heart failure
      (9.9 +/- 5.2 ng/mL) than in those with NYHA class II (4.9 +/- 1.9 ng/mL, P
      <0.0001). Detection of troponin T (> or =0.02 ng/mL) was also more common in
      patients with worse heart failure (81% [13/16] in class III or IV vs. 43% [17/40]
      in class II, P = 0.02). Significant correlations were found between heart-type
      fatty acid-binding protein levels and plasma levels of A-type natriuretic peptide
      (r = 0.45, P = 0.0004), B-type natriuretic peptide (r = 0.66, P <0.0001), and
      norepinephrine (r = 0.36, P = 0.006). Male sex (hazard ratio [HR] = 5.0; 95%
      confidence interval [CI]: 1.3 to 19), detectable troponin T levels (HR = 7.0; 95%
      CI: 1.1 to 44), heart-type fatty acid-binding protein (HR = 2.6 per 3.9-ng/mL
      increase; 95% CI: 1.1 to 6.5), and left ventricular ejection fraction (HR = 3.6
      per 15% decrease; 95% CI: 1.2 to 11) were independently associated with
      subsequent cardiac events (8 deaths or 10 readmissions because of worsening heart
      failure). CONCLUSION: Heart-type fatty acid-binding protein and troponin T are
      markers of ongoing myocardial damage, and are associated with subsequent cardiac
      events in patients with chronic heart failure.

PMID- 12517362
TI  - Conservative management of polymicrobial peritonitis complicating peritoneal
      dialysis--a series of 140 consecutive cases.
AB  - PURPOSE: Because polymicrobial peritonitis is believed to be caused by bowel
      perforation in peritoneal dialysis patients, surgical exploration is often
      recommended. However, there is recent evidence that antibiotic therapy may be a
      safe alternative. METHODS: We studied 140 consecutive episodes of dialysis
      related polymicrobial peritonitis from January 1995 to June 2001. All episodes
      were treated primarily with intraperitoneal antibiotics. When there was no
      response, the Tenckhoff catheter was removed, usually after about 10 days of
      treatment. Laparotomy was performed only when there was clinical suspicion of
      surgical pathology. RESULTS: Ninety patient-episodes (64%) responded to
      antibiotics alone by day 10; 56 patients (40%) had complete cure with no relapse
      in 4 months. Nine patients (6%) died within 2 days. Laparotomy was performed in 8
      patients who did not respond by day 10, but only 3 had underlying surgical
      disease (strangulated hernia, ischemic colitis, and colonic cancer). In a
      multivariate logistic regression analysis, age and the presence of fungus,
      anaerobes, or Pseudomonas species in the dialysis fluid were independent
      predictors of poor primary response; and presence of fungus was the only
      independent predictor of failure to cure in 4 months. CONCLUSION: Most patients
      with dialysis-related polymicrobial peritonitis responded to antibiotic therapy,
      and surgical exploration was needed only in a few patients. A careful examination
      of isolated organisms may help in identifying patients who need Tenckhoff
      catheter removal or surgical intervention.

PMID- 12517361
TI  - Cholesterol-lowering medication, cholesterol level, and reproductive hormones in
      women: the Women's Ischemia Syndrome Evaluation (WISE).
AB  - PURPOSE: Reproductive hormones such as estrogen, progesterone, and testosterone
      are synthesized from a common cholesterol precursor pathway. We hypothesized that
      use of statins and the resultant lower blood lipoprotein levels would be
      associated with lower reproductive hormone levels in women. We also sought to
      evaluate this association, independent of statin use, particularly among
      premenopausal women of childbearing age. METHODS: We enrolled 453 (114 pre-, 30
      peri-, and 309 postmenopausal) women with coronary risk factors (mean [+/- SD]
      age, 58 +/- 13 years) who were undergoing coronary angiography for suspected
      ischemia at four academic medical centers. Blood lipoprotein levels (total
      cholesterol, triglycerides, low-density lipoprotein [LDL] cholesterol, high
      density lipoprotein cholesterol) and serum reproductive hormone levels
      (estradiol, bioavailable estradiol, estrone, progesterone) were measured.
      RESULTS: Use of statins was associated with lower lipoprotein levels, but not
      lower reproductive hormone levels, in all women. Mean estradiol levels were not
      significantly lower among premenopausal women with very low LDL cholesterol
      levels compared with women with higher LDL cholesterol levels (estradiol: 71 +/-
      52 pg/mL vs. 88 +/- 67 pg/mL, P = 0.32). CONCLUSION: Among women undergoing
      coronary angiography for suspected myocardial ischemia, the use of statins, or
      lower cholesterol levels, are not associated with significantly lower levels of
      reproductive hormones.

PMID- 12517363
TI  - Bone mass and the risk of prostate cancer: the Framingham Study.
AB  - PURPOSE: To examine the relation of bone mass-a potential biologic marker for
      cumulative exposure to androgens, insulin-like growth factors, and calcium intake
      to subsequent development of prostate cancer. METHODS: We used radiogrammetry to
      measure the second metacarpal cortical area of 1012 white men with no history of
      prostate cancer who had undergone posteroanterior hand radiography between 1967
      and 1970. Participants were followed until the end of 1999. All incident cases of
      prostate cancer were confirmed histologically. We examined bone mass in relation
      to the risk of prostate cancer using a Cox proportional hazards model. RESULTS:
      During follow-up, 100 men developed prostate cancer. Incidence rates per 1000
      person-years were 3.8 among men in the lowest quartile of bone mass, 4.8 in the
      second quartile, 7.4 in the third quartile, and 6.5 in the highest quartile.
      Compared with men in the lowest quartile of bone mass, the multivariate-adjusted
      rate ratio was 1.3 (95% confidence interval [CI]: 0.7 to 2.5) for those in the
      second quartile, 1.9 (95% CI: 1.0 to 3.4) in the third quartile, and 1.6 (95% CI:
      0.9 to 3.0) in the highest quartile (P for trend = 0.06). CONCLUSION: Men with
      high bone mass may be at an increased risk of prostate cancer. Although the
      biological mechanisms underlying this relation are not understood, cumulative
      exposure to high levels of androgen, insulin-like growth factor 1, or calcium
      intake may be involved.

PMID- 12517364
TI  - Quality markers of drug information on the Internet: an evaluation of sites about
      St. John's wort.
AB  - PURPOSE: We aimed to evaluate websites about St. John's wort for the quality of
      their content, including accuracy as reflected by statement of correct indication
      and mentioning of interacting drugs, the presence of formal criteria as reflected
      by adherence to published standards for health information on the Internet, and
      the validity of individual formal criteria as markers of content quality.
      SUBJECTS AND METHODS: The Internet was searched with the metasearch engine
      WebFerret for sites about St. John's wort. A cross-sectional survey of a
      representative sample of randomly selected sites (n = 208) was performed. The
      main outcomes were the percentage of sites fulfilling the two criteria of content
      quality, the percentage of sites exhibiting eight formal criteria, and the
      associations between formal criteria and criteria of content quality, as
      determined by multivariate logistic regression analysis. RESULTS: Twenty-two
      percent (n = 45) of the websites correctly listed depression as the only
      indication for use of St. John's wort, and 22% (n = 46) identified at least one
      drug interaction with St. John's wort. Citing scientific publications was
      associated with mentioning the correct indication (odds ratio [OR] = 4.4; 95%
      confidence interval [CI]: 1.4 to 14) and mentioning of any interacting drug (OR =
      6.0; 95% CI: 2.0 to 18). Absence of financial interest was associated with
      mentioning the correct indication (OR = 5.4; 95% CI: 2.2 to 14) and interacting
      drugs (OR = 3.1; 95% CI: 1.2 to 7.7). CONCLUSION: The content quality of sites
      about St. John's wort was generally poor. Our results suggest that Internet users
      should prefer noncommercial sites that reference the information to scientific
      publications when searching for drug information.

PMID- 12517365
TI  - Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450
      metabolized drugs.
AB  - Drug-metabolizing enzyme activity is one of many factors affecting patient
      response to medications. The objective of this review is to highlight the
      potential for genetic variability in cytochrome P450 enzyme activity that can
      lead to interperson differences in response to drugs. Awareness and application
      of this knowledge will improve drug use in clinical practice and provide the
      physician with further appreciation that standard drug dosing may not be
      appropriate in all patients.

PMID- 12517366
TI  - Benign migratory glossitis or geographic tongue: an enigmatic oral lesion.
AB  - Benign migratory glossitis, or geographic tongue, is usually an asymptomatic
      inflammatory disorder of unknown etiology that affects the epithelium of the
      tongue. Local loss of filiform papillae leads to ulcer-like lesions that rapidly
      change the color and size. Histopathologic findings parallel the clinical
      appearance, and may have a psoriasiform pattern. The disorder is characterized by
      exacerbations and remissions. In most cases, patients do not require treatment
      other than reassurance about the benign nature of the disorder.

PMID- 12517367
TI  - Profound interferon gamma deficiency in patients with chronic pulmonary
      nontuberculous mycobacteriosis.

PMID- 12517368
TI  - Cases from the Osler Medical Service at Johns Hopkins University. Scedosporium
      apiospermum mycetoma of the lung.
AB  - PRESENTING FEATURES: A 42-year-old man was admitted with a chief complaint of
      cough and night sweats of 2 months' duration. The cough produced brown sputum but
      no blood. He also reported drenching sweats every night for the last several
      weeks before admission. He attributed his cough to exposure to dust while working
      on demolishing a funeral home 2 months ago; he denied any history of respiratory
      symptoms before this recent job. The patient smoked less than one pack of
      cigarettes per week during the previous year. He had no history of tuberculosis
      or contact with infected persons. He denied a history of severe lung infection,
      asthma, sinus disease, or overseas travel, as well as behaviors that are risk
      factors for human immunodeficiency virus (HIV) infection, such as intravenous
      drug use or multiple sexual partners.His physical examination was notable for a
      temperature of 101.4 degrees F and an oxygen saturation of 98% on room air. In
      general, he was thin, although well in appearance, and not visibly short of
      breath. His lungs were clear to auscultation. Laboratory studies and urinalysis
      were normal.A chest radiograph showed a 3-cm by 2-cm mass with a surrounding
      cavity in the right upper lobe (Figure 1). A subsequent chest computed
      tomographic scan showed a 5-cm by 4-cm cavity in the right upper lobe, with
      surrounding infiltrates as well as a mass within the cavity suspicious for a
      fungus ball (Figure 2). Patchy infiltrates were also seen in the left and right
      lower lobes. What is the diagnosis?

PMID- 12517369
TI  - Infodemiology: The epidemiology of (mis)information.

PMID- 12517370
TI  - Overlooking patient outcomes in a meta-analysis of trials of granulocyte colony
      stimulating factor.

PMID- 12517372
TI  - Point of maximal impulse and heart failure.

PMID- 12517373
TI  - Advances in the Internal medicine subinternship.

PMID- 12517374
TI  - Improved collection and developmental competence of immature macaque oocytes.
AB  - Methods previously described to aspirate immature oocytes from ovaries of
      macaques result in approximately half the oocytes being stripped of cumulus
      cells. Here, we describe modifications of the needle aspiration assembly that
      yield much higher percentages of cumulus-intact oocytes when used with an
      ultrasound-guided method for oocyte recovery in monkeys. Sealing of the needle
      assembly appears to stabilize vacuum pressure at the needle tip and prevents air
      from entering the tubing. Reduction of the vacuum pressure from -100 to -20 kPa
      resulted in a significant decrease of denuded oocytes from over 50% to fewer than
      10%. This was accompanied by a significant increase in the percentage of oocytes
      that developed into blastocysts after in vitro fertilization. Reduction of the
      aspiration pressure below -20 kPa significantly reduced the total number of
      oocytes recovered. We concluded that these modifications represent the best
      compromise to collect the largest number of cumulus-intact oocyte complexes from
      macaques.

PMID- 12517375
TI  - Buffalo and cattle hybrid embryo development is decreased by caffeine treatment
      during in vitro fertilization.
AB  - Water buffalo are renowned for difficulties in the implementation of assisted
      reproductive technologies, with both males and females being problematic. In this
      study, we used cattle oocytes to assess the effect of treatments with heparin and
      caffeine on buffalo spermatozoa and subsequent fertilization and embryo
      development in vitro. There was no significant difference between buffalo and
      bovine spermatozoa in the events associated with fertilization. Fertilization of
      cattle oocytes with buffalo spermatozoa resulted in 7.8% of oocytes developing
      into hybrid embryos. A difference in the developmental capability of hybrid
      embryos compared with the cattle control was observed. This has not been
      previously reported. The subsequent transfer of a limited number of hybrid
      embryos did not produce a viable pregnancy. However, control treatments in this
      experiment also failed to achieve pregnancy, so objective data is not available
      to provide conclusions about the developmental competence of the buffalo and
      cattle hybrid embryos. Optimal spermatozoa capacitation treatments achieved 61%
      fertilization and 21% zygote cleavage into two cell embryos. There was no
      significant difference in fertilization or development due to heparin or
      spermatozoa concentrations. However, treatment of buffalo and cattle spermatozoa
      with caffeine significantly decreased embryo cleavage but also tended to decrease
      embryo development to the blastocyst stage. These studies suggest that problems
      with reproduction in buffalo may reside with biological mechanisms associated
      with the oocyte that are often complicated by poor male reproductive performance.
      Selection for bull fertility would prevent some of these complications.

PMID- 12517376
TI  - Stage-specific effects of the osmolarity of a culture medium on the development
      of parthenogenetic diploids in the pig.
AB  - The objective of this study was to investigate the effects of osmolarity of
      culture media on the development of porcine parthenogenetic diploids. Oocyte
      cumulus-granulosa cell complexes were collected from ovaries and then in vitro
      cultured for 48 h. The mature oocytes were subjected to a single electro
      stimulation (El-St; 100 micros, 1500 V/cm), treated with 5.0 microg/ml
      Cytochalasin B for 4h and then cultured under various conditions as described
      below. In Experiment 1, the diploids were cultured for 168 h after El-St in
      modified Whitten's medium with 256 mOsmol (mWM256), mKRB with 309 mOsmol, and mWM
      with 309 mOsmol (mWM309), in which the osmolarity was adjusted by addition of
      NaCl or mannitol, or by reduction of distilled water. In Experiment 2, the
      diploids were cultured in the five media used in Experiment 1 for the first 48 h,
      and then in mWM256 until 168 h after El-St. In Experiment 3, the diploids were
      cultured for the first 48 h in mWM with osmolarity adjusted from 256 to 330
      mOsmol by addition of NaCl for the first 48 h and then in mWM256 until 168 h
      after El-St. In Experiment 4, the diploids were cultured in mWM with 290 mOsmol
      (mWM290) for the first period of 24, 48, or 72 h, and then in mWM256 until 168 h
      after El-St. In Experiment 5, after diploids were cultured in mWM290 for the
      first 48 h, the obtained 4-cell diploids were transferred to mWM with osmolarity
      adjusted from 200 to 310 mOsmol by addition of NaCl, then cultured until 168 h
      after El-St. All media were supplemented with 0.5mg/ml hyaluronic acid and
      4.0mg/ml bovine serum albumin. The results obtained in Experiments 1-5 indicate
      that the osmolarity of a medium, but not the Na(+)/K(+) ratio, exerts effects on
      the development of diploids to the blastocyst stage. The change of osmolarity of
      the culture media after the 4-cell stage increased the rate of expanded
      blastocyst formation in porcine diploids. The optimal osmolarities of culture
      medium for the first 48 h after El-St (before the 4-cell stage) were 290 and 280
      320 mOsmol, and those for the later period (after the 4-cell stage) were 256 and
      220-270 mOsmol, respectively.

PMID- 12517377
TI  - Effects of dead spermatozoa on motion characteristics and membrane integrity of
      live spermatozoa in fresh and cooled-stored equine semen.
AB  - The aim of this study was to determine if dead spermatozoa reduced motility or
      membrane integrity of live spermatozoa in fresh and cooled-stored equine semen.
      Three ejaculates from each of three stallions were centrifuged and virtually all
      seminal plasma was removed. Spermatozoa were resuspended to 25 x 10(6)
      spermatozoa/ml with EZ-Mixin CST extender and 10% autologous seminal plasma, then
      divided into aliquots to which 0 (control), 10, 25, 50, or 75% (v/v) dead
      spermatozoa were added. Dead spermatozoa preparations contained 25 x 10(6)
      spermatozoa/ml and 10% seminal plasma from pooled ejaculates of the three
      stallions, in EZ-Mixin CST extender. Spermatozoa were killed in the pooled
      ejaculates by repeated freezing and thawing, then stored at -20 degrees C until
      warmed to 37 degrees C and mixed with aliquots of fresh spermatozoa to be cooled
      and stored in an Equitainer for 24h. Motion characteristics (% total motility
      (MOT), % progressive motility (PMOT), and mean curvilinear velocity (VCL)) for
      fresh and 24h cooled samples were determined using a computerized spermatozoal
      motion analyzer. The presence of up to 75% dead spermatozoa did not adversely
      affect MOT or PMOT of live spermatozoa in either fresh or cooled-stored semen.
      However, VCL and the percentage of membrane-intact spermatozoa were reduced
      compared to control samples when 75% (v/v) dead spermatozoa were added. Membrane
      integrity, as assessed by staining with carboxyfluoresein diacetate-propidium
      iodide, was highly correlated (r>0.8; P<0.001) with MOT and PMOT in both fresh
      and cooled-stored semen samples. Results of this study have application to the
      processing of both cooled and frozen equine semen.

PMID- 12517378
TI  - Cryopreservation of canine semen using a coconut water extender with egg yolk and
      three different glycerol concentrations.
AB  - Semen was collected by digital manipulation from six adult dogs. The second
      fraction of the ejaculate was used in this study. The semen was assessed by
      macroscopic and microscopic criteria 1 min after collection, first dilution,
      cooling, glycerol addition and thawing. Experiments were conducted to compare the
      effect of three different concentrations of glycerol in coconut water extender.
      The freezing method employed was that one described for caprine semen with slight
      changes. Semen was thawed at 37 degrees C for 1 min. Spermatozoal motility after
      thawing was 49.2+/-26, 44.2+/-18.3 and 35.8+/-26.8% for groups with 4, 6 and 8%
      glycerol, respectively. The vigor after thawing was 2.6+/-1.1, 2.7+/-1.0 and
      2.1+/-1.2 for these groups, respectively. There was no difference among groups in
      motility and vigor. However, a smaller percentage of total and secondary
      abnormalities was observed using 6% glycerol in coconut water extender. In
      conclusion, the three glycerol concentrations (4, 6 or 8%) can be used
      successfully in cryopreservation of canine semen using a coconut water extender.

PMID- 12517379
TI  - Reproductive period affects lipid composition and quality of fresh and stored
      spermatozoa in Turkeys.
AB  - Semen of Turkeys between 31 and 52 weeks of age was analyzed to investigate the
      cause of reduction in Turkey fertility at the end of the reproductive period.
      Sperm motility and viability, lipid concentration, fatty acid composition and
      lipid peroxides were evaluated on fresh spermatozoa or spermatozoa stored for 48h
      at 4 degrees C. Fertility of fresh semen was also evaluated. Fertility obtained
      with fresh semen decreased at 44-47 weeks of age. Ageing was also accompanied by
      a decrease in sperm viability (at 47 weeks) and later by a decrease in motility
      of spermatozoa (at 52 weeks). Polyunsaturated fatty acids (PUFAs) were the first
      lipids of fresh spermatozoa affected by age, especially n-3 and n-9 PUFAs.
      Changes in these PUFAs were followed by a 30% increase in lipid peroxidation at
      47 and 52 weeks of age and a reduction in phospholipid content at 52 weeks. In
      vitro storage did not cause lipid peroxidation in sperm obtained during the first
      half of the reproductive period but malondialdehyde (MDA) levels significantly
      increased in sperm obtained during the second half of this period. In vitro
      storage also decreased phospholipid content of spermatozoa from 41 weeks of age,
      and viability and motility regardless of age. In conclusion, lipid alteration
      mainly originating from PUFAs peroxidation could partly explain the decrease in
      semen quality and fertility observed with ageing. In addition, lipid peroxidation
      was increased during in vitro storage of spermatozoa from older Turkeys.

PMID- 12517380
TI  - Effect of ovary storage and oocyte transport method on maturation rate of horse
      oocytes.
AB  - Two experiments were conducted to determine the effects of storage on equine
      ovaries or isolated oocytes. Ovaries were collected at an abattoir and were
      maintained at room temperature during collection and transport (3-9h total).
      After arrival at the laboratory, ovaries were divided into three groups:
      immediate oocyte collection (control), storage at room temperature overnight (15
      18 h) before oocyte collection, or storage at 4 degrees C overnight before oocyte
      collection. Collected oocytes were cultured in maturation medium for 24h. There
      was a significant increase in the proportion of oocytes classified as having
      compact cumuli in the two storage groups when compared with the controls. For
      oocytes originally having expanded cumuli, the rate of maturation to MII was
      significantly higher in the control group (72%) than in either storage group, and
      the maturation rate for oocytes from ovaries stored at room temperature (27%) was
      significantly higher than that for ovaries stored at 4 degrees C (10%). A similar
      trend was seen for oocytes originally having compact cumuli (24, 11, and 3% in MI
      II for control, room temperature, and cold groups, respectively). In Experiment
      2, we evaluated the effect of different packaging systems on the maturation of
      horse oocytes within a portable incubator. Use of 1 ml of equilibrated maturation
      medium in a 1 ml glass vial was associated with maturation equivalent to that for
      standard incubation.

PMID- 12517381
TI  - Effects of pregnant mare serum gonadotropin (eCG) on follicle development and
      granulosa-cell apoptosis in the pig.
AB  - The effect of eCG on follicular development and granulosa-cell apoptosis in
      sexually mature and immature gilts and on granulosa-cell apoptosis in vitro were
      studied. The sexually mature gilts were treated with eCG on Day 11 of the estrous
      cycle, and effects were analyzed at different times after treatment with
      untreated animals at corresponding stages of the cycle as controls. Apoptosis was
      determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL), hematoxylin and eosin staining, and DNA ladder. The proportion
      of apoptotic cells in atretic follicles (39%) was significantly higher (P<0.01)
      than that in healthy follicles (9%). At 24h after eCG treatment in mature gilts,
      the total number of follicles visible on the ovarian surface (57 per ovary), the
      number of small (<3mm) follicles (31.5 per ovary) and the number of medium-sized
      (3-5mm) follicles (23 per ovary) were significantly higher (P<0.05) than those of
      control animals (28, 20 and 6.5 per ovary, respectively), and declined gradually
      thereafter to below the level of control animals. The number of large (>or=5mm)
      follicles began to show a marked increase at 72h after eCG (8.5 versus 2.5,
      P<0.05). At 24h after eCG treatment, the proportions of apoptotic cells in small
      (7.2%) and medium-sized follicles (7.4%) were markedly lower (P<0.01) than those
      in controls (21.5 and 21%, respectively) and increased gradually thereafter to
      approach the level in controls. The percentage of apoptotic cells in large
      follicles (10% at 24h post-eCG) did not change significantly. Before eCG
      treatment, there were markedly fewer follicles of all types on ovaries of
      immature gilts than of mature gilts (9 versus 25 per ovary) and the proportion of
      apoptotic cells in small and medium follicles was high (25 and 34%,
      respectively). After eCG treatment, the changes in follicle number and proportion
      of apoptotic cells in the immature gilts followed a similar pattern to that of
      the mature gilts. Equine chorion gonadotropin inhibited apoptosis of granulosa
      cells cultured either in vitro or in intact follicles in a dose-dependent manner.
      Thus, follicular atresia in the pig, as in other animals, was characterized by
      apoptosis of large numbers of granulosa cells, and eCG promoted follicular
      development by inhibition of granulosa-cell apoptosis.

PMID- 12517382
TI  - Lymphocyte-mediated lysis of sheep chorion: susceptibility of chorionic cells to
      third-party and maternal cytotoxic lymphocytes and presence of cells in the
      endometrium exhibiting cytotoxicity toward natural-killer cell targets.
AB  - In several species, the trophoblast is resistant to lysis by cytotoxic
      lymphocytes. Such resistance is believed to contribute to survival of the
      semiallogenic conceptus. We tested whether ovine chorionic cells are susceptible
      to lysis by specific and nonspecific cytotoxic lymphocytes in peripheral blood
      (PBL) and whether cytotoxic cells that can lyse target cells for natural-killer
      cells are present in the endometrium. Primary chorionic cells from pregnant ewes
      at Days 51-91 of gestation were labeled with 51Cr and incubated for 20 h at 50:1
      and 100:1 ratios with PBL from the pregnant mother or from a third-party ewe. In
      the absence of interleukin-2 (IL-2), there was no killing of primary chorionic
      cells by third-party PBL even after infection of chorionic cells with bovine
      herpes virus-1. Incubation with IL-2-induced cytotoxic action in third-party PBL
      towards one of six primary chorionic cell preparations only. Primary chorionic
      cells from two of four placentae were lysed by maternal PBL. Luminal epithelial
      cells from cyclic ewes and from the pregnant and nonpregnant uterine horns of
      unilaterally-pregnant ewes were evaluated for the presence of cells capable of
      killing D17 target cells (a natural-killer cell target). Killing was observed but
      there was no difference in activity between physiological stages. In contrast,
      there was intense immunochemical localization of perforin in glandular and
      luminal endometrial epithelial cells in pregnant ewes, and less intense staining
      in nonpregnant animals. It is concluded that ovine chorionic cells are generally
      resistant to killing by natural-killer-like cells and lymphokine-activated killer
      cells. Generation of maternal cytotoxic lymphocytes against trophoblast can occur
      in some cases and may contribute to pregnancy loss.

PMID- 12517383
TI  - Effects of body condition score and score change on the reproductive performance
      of dairy cows: a meta-analysis.
AB  - A meta-analysis was conducted to evaluate the effects of body condition score
      (BCS) at parturition and at first AI, and of body condition change during the
      early lactation period on the variables pregnancy rate at first AI and number of
      days open in dairy cattle. Inclusion criteria for the publications were:
      comparison of at least two groups of animals of different categories of BCS or
      change (independent variables) and consideration of pregnancy rate at first AI or
      number of days open (dependent variables). Fifteen papers were selected and 23
      excluded. Data corresponding to 7733 cows from 11 studies described in 10 papers
      were included in the analysis of pregnancy rate at first AI, and those derived
      from 4529 cows from 11 studies described in 10 papers were used to analyze
      effects on the number of days open. Analyses were stratified according to study
      design and milk production characteristics. We defined low, intermediate and high
      categories of BCS for values lower than 2.5, from 2.5 to 3.5, or higher than 3.5,
      respectively. The categories of body condition change were increase (gain in
      score), slight loss (0-0.5 point loss), moderate loss (0.6-1 point loss), and
      severe loss (over 1 unit loss). Intermediate body condition at parturition and at
      first AI, and a slight loss during the early lactation period were used as
      reference categories. The effects of body condition on the variable pregnancy
      rate at first AI were highly heterogeneous, while all the studies considering the
      number of days open presented homogeneous results. A clear association between
      body condition category and pregnancy rate at first AI was detected only when the
      effect of a low score at parturition was analyzed: pregnancy rate at first AI
      significantly decreased by about 10% in cows delivering in poor condition.
      Animals with a high BCS at parturition showed a significant reduction in the
      number of days open of 5.8 or 11.7 when compared with animals with an
      intermediate or low body condition, respectively. In animals in the high body
      condition category at first AI, the variable days open showed a significant drop
      of 11.9 or 24.1, compared to animals in the intermediate or low categories,
      respectively. A severe loss in score during early lactation was related to a
      significant (10.6) increase in the number of days open, while a slight or
      moderate body condition change, either loss or gain in score, was not
      significantly related to the variable days open. We found that the number of days
      open was a good indicator of the effects of BCS or change in score on
      reproductive performance in dairy cattle. The variable pregnancy rate at first
      AI, however, yielded heterogeneous results among studies.

PMID- 12517384
TI  - Recovery and cryopreservation of sika deer (Cervus nippon) spermatozoa from
      epididymides stored at 4 degrees C.
AB  - The aim of this study is to clarify influence of cold storage of deer
      epididymides on sperm quality and suitability for cryopreservation. The
      epididymides were obtained postmortem from sika deer during the breeding season.
      When epididymides were removed 8-12h postmortem and stored at 4 degrees C for 1-4
      days, the collected spermatozoa showed low motility (6.4%). When spermatozoa were
      collected from epididymides removed within 4h postmortem, sperm motility and
      viability were 71.8 and 82.4%, respectively. Sperm motility decreased as
      prolongation of the storage period of the epididymides continued up to 7 days,
      but sperm viability was not affected. Pyknosis of the epithelial cells and their
      release into the lumen were observed in the stored epididymides. Epididymal
      spermatozoa frozen on Day 0 showed 58.1% motility and 83.2% viability. Motility
      of the frozen-thawed spermatozoa from epididymides stored at 4 degrees C for 1
      day (41.9%) was similar to that of nonfrozen spermatozoa from epididymides stored
      for 4 days (41.8%). These results suggest that refrigeration of deer epididymides
      or cryopreservation of spermatozoa from refrigerated epididymides can be used for
      assisted reproductive techniques when epididymal spermatozoa cannot be collected
      immediately.

PMID- 12517385
TI  - Quality of canine semen submitted to single or fractionated glycerol addition
      during the freezing process.
AB  - Glycerol is the cryoprotector most frequently used to freeze semen from different
      species. The objective of the present study was to compare the effect of single
      and fractionated glycerol addition on canine semen quality after thawing. Sperm
      fractions from 12 stud dogs were collected, evaluated, extended in Tris plus egg
      yolk and separated into two aliquots to which glycerol was added in one step
      (single) or in three steps at 5-min intervals (fractionated). Semen was frozen
      and stored in liquid nitrogen and thawed after 1 week. A thermoresistance test
      was performed over a period of 120 min at 37-39 degrees C to evaluate the
      percentage of mobile spermatozoa (motility) and the status of motility (vigor)
      after thawing. There were no significant differences between the two methods of
      glycerol addition-immediately after thawing, and during the thermoresistance test
      in sperm motility, vigor or morphology. A significant reduction in motility and
      vigor was found at 15 min after thawing and these parameters continued to decline
      until 120 min. In conclusion, glycerol can be added to canine semen in single or
      fractionated manner, but the single addition method is the easiest and the most
      practical to use.

PMID- 12517386
TI  - Production of transgenic goats by pronuclear microinjection of in vitro produced
      zygotes derived from oocytes recovered by laparoscopy.
AB  - Oocytes collected by laparoscopic ovum pick-up (LOPU) were successfully used to
      produce transgenic goats by pronuclear microinjection of in vitro zygotes. Estrus
      cycles of 109 donor goats were synchronized using intravaginal sponges
      impregnated with 60 mg of medroxyprogesterone acetate and treatment with 70 mg
      NIH-FSH-P1 and 300 IU eCG to stimulate follicular development. Follicles were
      aspirated under laparoscopic observation. In vitro maturation (IVM) of oocytes
      was performed in M199 supplemented with hormones, kanamycin and 10% estrus goat
      serum. Following IVM, oocytes were cocultured with capacitated semen in TALP
      supplemented with 20% estrus goat serum for 15-20 h. The resulting zygotes were
      microinjected with a linear DNA fragment. In total, 3293 follicles were aspirated
      (15.7+/-9 follicles aspirated per donor) and 2823 oocytes were recovered (13.4+/
      8 oocytes per donor). A total of 1366 zygotes were microinjected and transferred
      into 219 recipient goats by midventral laparotomy (average 6.2 embryos per
      recipient). A total of 150 kids were born, of which 9 (6 M: 3 F) were confirmed
      to be transgenic by PCR and Southern blotting analyses. These results demonstrate
      that acceptable transgenesis rates can be obtained in goats by DNA microinjection
      of in vitro produced zygotes.

PMID- 12517387
TI  - Male-specific DNA sequences in pigs.
AB  - One hundred primers (Operon kits OPAA, OPAO, OPAV, OPC, and OPE series) were used
      for random amplified polymorphic DNA (RAPD) fingerprinting to determine male
      specific fragments. Seventy-four percent of the primers yielded Yorkshire
      polymorphic fragments. One of these primers, OPAV-18, produced a novel 1098-bp
      DNA fragment found only in tested males. This male-specific fragment was isolated
      and constructed into plasmids for nucleotide sequencing. Two primers (5'
      TTGCTCACGG TAGATAACAA GAGAG-3' and 5'-TTGCTCACGG ACCAGGTAGG GAATG-3') were
      designed according to the cloned male-specific sequence to amplify the male
      specific band using polymerase chain reaction (PCR) for pig sexing. Sex-specific
      bands in the PCR gel products were represented in males but none were found in
      females when Yorkshire, Duroc, and Landrace genomic DNA samples were amplified
      with these two primers by PCR. The PCR products in the gel were transferred to
      nylon membranes and hybridized with a 32P-dCTP labeled probe of the cloned male
      specific DNA fragment. There was a clear hybridization signal in samples from all
      of the male pigs, but not from those of female pigs. Male and female genomic DNA
      samples from these pigs were spotted onto nylon membranes and hybridized with the
      male-specific probe. The probe hybridized strongly to males only. A high degree
      of sequence homology was found among the novel male-specific DNA sequences in
      Yorkshire, Duroc and Landrace. The sex of these three breeds of pigs could be
      easily and effectively determined using these two primers.

PMID- 12517388
TI  - Effects of different sexual stimuli on oxytocin release, uterine activity and
      receptive behavior in estrous sows.
AB  - This study was designed to assess effects of exogenous oxytocin (OT) on uterine
      activity, and to compare three different sexual stimuli in their effects on OT
      release, uterine activity and receptive behavior in estrous sows. Uterine
      activity was recorded nonsurgically, by transcervical insertion of an open-end
      catheter into the caudal part of the uterine lumen. After recording spontaneous
      uterine activity, exogenous OT was administered (Experiment 1), or one of the
      following stimuli was applied to the sow (Experiment 2): tactile stimuli, i.e.
      manual stimulation of the sow's back and flanks, tactile stimulation in
      combination with boar pheromone spray (5alpha-androstenon), or tactile stimuli in
      the presence of a boar. Both exogenous OT and endogenously released OT increased
      uterine activity. The effect depended on the uterine activity before treatment,
      with the effect being greater in those sows with lower uterine activity before
      treatment. In Experiment 2, boar presence was the only stimulus that elicited a
      clear, surge-like release of OT, and also clearly increased uterine activity.
      Release of OT was not necessary for induction of receptive behavior: tactile
      stimulation alone and in combination with pheromone spray elicited a standing
      response in one third of the sows, but had no effect on OT release.

PMID- 12517389
TI  - Effects of thioredoxin on the preimplantation development of bovine embryos.
AB  - Thioredoxin (TRX) is an ubiquitous protein disulfide reductase, which is known to
      be involved in the implantation development of mouse embryos. In the present
      study, recombinant human TRX was used to evaluate its effect on the promotion of
      preimplantation development of bovine embryos derived from in vitro maturation
      and fertilization. Supplementation of the medium 24h post insemination with TRX
      significantly (P<0.05) enhanced the frequency of development to the blastocyst
      stage in 5% O(2) concentration. The optimal concentration was 0.5 microg/ml
      (P<0.05, compared with 0, 0.1 and 1.0 microg/ml). This effect of TRX was evident
      only when added around the time of the first cleavage stage (24 h post
      insemination); no promotion was found with treatment at 6h (one-cell) or 44 h
      (six- to eight-cell) after insemination. Moreover, it is of interest that even
      with the best combination of the dose and timing of TRX treatment (0.5 microg/ml,
      at 24 h post insemination), no promotion of development was observed when embryos
      were cultured under 20% O(2). However, a preincubation of TRX in the culture
      medium under 20% oxygen for 24h did not diminish the promoting effect in the
      subsequent TRX treatment under optimal conditions, thus suggesting that the
      possible oxidation of TRX alone may not be the reason for the disappearance of
      the effect under a high oxygen concentration. These results indicate that TRX
      does improve the development of bovine embryos in vitro, though unlike the
      general reducing reagents such as beta-mercaptoethanol or cysteamine, TRX may
      have to exert its effect at specific times and in more physiologic oxygen
      environments.

PMID- 12517390
TI  - Cryopreservation of semen from endangered pheasants: the first step towards a
      cryobank for endangered avian species.
AB  - In order to improve the genetic management of bird species within the European
      Endangered Programs (EEP), a research project on artificial insemination and
      cryopreservation of Galliformes semen has been developed. The aim of the program
      is to create a sperm cryobank for threatened bird species. During this study,
      semen was collected from 17 pheasant species and specific characteristics of
      ejaculates were analyzed (volume, sperm concentration, motility, pH). Artificial
      insemination with fresh semen was performed in nine species and with frozen semen
      in eight species. Inseminations with frozen and thawed semen were made in 17
      species. Viability of fresh and frozen semen was assessed in vitro using double
      stains, eosin and nigrosin. The effect of pH (7-8.5) on viability of fresh and
      frozen/thawed spermatozoa was also studied. Chicks hatched in eight and three
      species after insemination with fresh and frozen/thawed semen, respectively.
      Species varied widely in semen viability: 1-30% of spermatozoa survived freezing
      and thawing. There was a negative correlation between the viability of frozen
      spermatozoa and semen pH. In our experimental conditions, the pH of diluents had
      no effect on semen viability. However, semen with the highest pH had the lowest
      quality after freezing and thawing. These experiments demonstrated the
      feasibility of using a very simple and inexpensive method to achieve artificial
      insemination and cryopreservation of semen in endangered pheasant species.

PMID- 12517391
TI  - Use of two replacements of serum during bovine embryo culture in vitro.
AB  - This study evaluated the effect of two commercial serum replacements (Ultroser G
      and CPSR-3 on in vitro bovine embryo culture. In Experiment 1, zygotes were
      cultured in SOF+Ultroser G (2, 4 and 6%), SOF+CPSR-3 (2, 4 and 6%), and SOF+5%
      FCS (control). Blastocyst rates obtained after culturing with Ultroser G were
      lower than those with FCS. However, blastocyst rates for CPSR-3 were similar to
      those for serum. In addition, embryos produced in SOF+CPSR-3 had the same
      proportion inner cell mass number and total cell number as embryos cultured with
      FCS. In Experiment 2, a combination of serum replacements during different
      periods showed that treatment before the five-to eight-cell stages had no effect
      on further embryo development. However, treatments up to the morula stage
      affected blastocyst formation. The concentration of supplement and the timing of
      its inclusion in culture markedly affected embryo development. The serum
      replacement CPSR-3 can supplement embryo culture with blastocyst rates and
      quality similar to those for serum.

PMID- 12517392
TI  - Activity of angiotensin-converting enzyme (ACE) in reproductive tissues of the
      stallion and effects of angiotensin II on sperm motility.
AB  - A testis-specific isoform of angiotensin-converting enzyme (ACE) has been
      identified in a number of mammalian species. The purpose of this study was to
      characterize the activity of ACE in equine spermatozoa, seminal plasma, and
      testis. Activity of ACE was determined in seminal plasma, ejaculated and
      epididymal spermatozoa from mature stallions as well as from pre- and
      postpubertal testis. The effect of addition of angiotensin II on equine sperm
      motility was also evaluated. The activity of ACE in detergent extracted sperm
      plasma membrane was approximately 13-fold higher than that detected in seminal
      plasma (93.7 mU/mg versus 7.0 mU/mg protein, respectively). Activity of ACE in
      equine testis was significantly higher in postpubertal than in prepubertal males
      (3.0 mU/mg versus 0.4 mU/mg protein, respectively), and ACE activity was reduced
      (P<0.001) in a dose-dependent fashion by the addition of captopril. The effect of
      angiotensin II on sperm motility was evaluated by computer-assisted semen
      analysis in sperm incubated with angiotensin II (0, 1, 10, 100 nM) at 38.5
      degrees C. There was no significant effect of angiotensin II on the percent
      motile sperm; however, there was a significant main effect of angiotensin II
      (P<0.01) on the kinematic parameters beat cross frequency (BCF), average path
      velocity (VAP), and curvilinear velocity (VCL), respectively. In addition, there
      were significant stallionxconcentration interactions for amplitude lateral
      movement (ALH), BCF, linearity (LIN), straightness (STR), and VCL. This study
      demonstrates that ACE activity is present in sperm membrane from ejaculated and
      epididymal spermatozoa and in postpubertal testis. Further studies are required
      to determine the role of this testis-specific enzyme.

PMID- 12517393
TI  - Components of litter size in gilts with different prolactin receptor genotypes.
AB  - Behavioral estrus and components of litter size at Day 35/36 of pregnancy were
      studied in gilts with prolactin receptor (PRLR) genotype AA (n=9), AB (n=25), and
      BB (n=22). This PRLR polymorphism (two alleles, A and B) has been associated with
      litter size, although it is not known whether the polymorphism itself causes
      differences in litter size or whether it is a marker for a closely linked
      causative gene. Estrus length in three successive estrous cycles was not affected
      by genotype, but estrous cycle length tended (P<0.1) to be longer for AA gilts
      compared to AB and BB gilts. AA gilts had a significantly (P<0.05) higher
      ovulation rate (21.5+/-0.9) than BB gilts (18.7+/-0.6), resulting in a
      numerically higher number of embryos at Day 35/36 (17.0+/-1.3, 15.6+/-0.8, and
      13.7+/-0.9 for AA, AB, and BB gilts, respectively) which may lead to a subsequent
      difference in litter size. Ovulation rate of AB gilts (20.0+/-0.5) was
      intermediate. Genotype affected the total weight of the ovaries (P<0.05). Even
      after subtraction of the total weight of corpora lutea, ovarian weight in AA
      gilts was highest (16.6+/-1.0 g), in BB lowest (13.4+/-0.6g), and in AB gilts
      intermediate (15.0+/-0.6g; P<0.05). Unlike AB gilts, in AA and BB gilts uterine
      length was adapted to litter size, which led to longer (P<0.05) uteri for AA
      gilts (669+/-28 cm) compared to BB gilts (566+/-18 cm). Furthermore, embryos of
      AA gilts had heavier placentae (52.5+/-3.4 g) and larger implantation surface
      areas (309+/-19 cm(2)) than embryos of BB (42.0+/-2.3g, P<0.05; 256+/-12 cm(2),
      P<0.1) or AB (43.2+/-2.0 g, P<0.1; 257+/-11 cm(2), P<0.05) gilts. Results of this
      experiment show that the PRLR gene or a very closely linked gene affects porcine
      ovaries, uterus, and placenta in a way that might lead to differences in litter
      size. Since other genes and also environmental factors, however, might change the
      effect within the 112 days to parturition, it is preferable to state that the
      PRLR gene is a candidate gene for ovulation rate rather than for litter size.

PMID- 12517394
TI  - The association between lameness, ovarian cysts and fertility in lactating dairy
      cows.
AB  - The objective of this observational study was to evaluate the association between
      lameness, ovarian cysts, and fertility in lactating dairy cows. Data analysis of
      historical records from a 3000 Holstein farm was conducted. Sixty-five cows that
      became lame within 30 days postpartum were used as cases, and 130 nonlame cows
      served as controls. The outcome variables were incidence of ovarian cysts (OC,
      %), conception rate at first service (CRFS, %), overall pregnancy rate (PR, %),
      and calving to first service interval (CFSI, day), Incidence of OC and CRFS were
      analyzed by logistic regression, PR by survival analysis and CFSI by ANOVA. Lame
      cows had a lower CRFS (17.5% versus 42.6%) and higher incidence of OC (25.0%
      versus 11.1%) than controls (P<or=0.05). Calving to first service interval was
      not different between lame and control cows (P>0.05). There was a
      multicollinearity relationship between lameness and ovarian cysts. The results
      show that cows that became lame within the first 30 days postpartum were
      associated with a higher incidence of ovarian cysts, a lower likelihood of
      pregnancy, and lower fertility than control cows. Because this is an
      observational study it is not possible to conclude a cause-effect relationship.

PMID- 12517395
TI  - Antioxidant requirements for bovine oocytes varies during in vitro maturation,
      fertilization and development.
AB  - Antioxidants may be beneficial additives to synthetic culture media because these
      well defined media lack serum or other macromolecules that serve as reactive
      oxygen species scavengers. In this study, three separate experiments were
      performed to determine the effects of antioxidants on the development of oocytes
      to the morula and blastocyst stage when added during in vitro maturation (IVM) of
      bovine oocytes, during in vitro fertilization (IVF), and during embryo culture
      for the first 72 h of the development period. Bovine oocytes were matured,
      fertilized (under 20% O(2)), and embryos were cultured (under 7% O(2)) in defined
      conditioned medium in vitro with or without supplementation with the antioxidant
      cysteine, N-acetyl-L-cysteine (NAC), catalase and superoxide dismutase (SOD).
      Significant improvements in the proportion of oocytes undergoing morula and
      blastocyst development (33.3% versus 20.3%, P<0.05) were achieved when cysteine
      (0.6 mM) was added to the maturation medium as compared to control medium without
      antioxidant supplementation. However, the addition of NAC (0.6mM), catalase (5 or
      127 U/ml) or SOD (10 or 1000 U/ml) to the maturation medium did not improve the
      proportion of oocytes undergoing morula and blastocyst development. During the
      IVF period, addition of antioxidants (cysteine or NAC 0.6mM, catalase 127U/ml,
      SOD 100U/ml) significantly reduced the subsequent rate of bovine embryo
      development to the morula and blastocyst stage (P<0.05). In a defined medium for
      embryo culture (7% O(2)), the addition of cysteine improved the development of
      bovine embryos while NAC, catalase and SOD had no positive effect on embryonic
      development. Our study showed that medium supplementation with cysteine during
      IVM and in vitro culture (IVC) improved the rate of bovine embryo development, in
      contrast to extracellular antioxidants like catalase and SOD that caused no
      improvement.

PMID- 12517396
TI  - Comparison of two protocols for the treatment of retained fetal membranes in
      dairy cattle.
AB  - Two protocols for the treatment of retained fetal membranes in dairy cattle were
      evaluated in a field trial. Cows that retained the fetal membranes for more than
      12h were assigned to two treatment groups in an alternating order. In both groups
      rectal temperature was measured daily for 10 days after enrollment. In Group 1
      (n=35) cows with a rectal temperature >or=39.5 degrees C received a systemic
      antibiotic treatment with 600mg ceftiofur intramuscularly on three consecutive
      days. No manual removal of the fetal membranes or intrauterine treatment was
      conducted. In case of elevated temperature of >or=39.5 degrees C on Day 3
      treatment was conducted for another 2 days. In Group 2 (n=35) cows received a
      local antibiotic treatment (2500 mg ampicillin, 2500 mg cloxacillin) and an
      attempt was made to remove the fetal membranes manually. In case of a rectal
      temperature >or=39.5 degrees C 6000 mg of ampicillin were administered
      intramuscularly. Treatment was repeated on three consecutive days. If temperature
      did not decrease below 39.5 degrees C systemic treatment was extended for another
      2 days. During 10 days of observation 33 and 34 cows showed fever, i.e. a body
      temperature >or=39.5 degrees C in Groups 1 and 2, respectively (94.3 versus
      97.1%). The proportion of cows considered as cured (temperature <39.5 degrees C
      on Day 10 after enrollment) was 65.7 and 68.6% in Groups 1 and 2, respectively.
      All cows showed signs of chronic inflammation of the genital tract on Day 14
      after calving. Within 4 weeks postpartum three (8.6%) and four (11.4%) cows were
      culled in Groups 1 and 2, respectively. Days to first service and days open did
      not differ significantly between the groups. Proportion of cows pregnant on Day
      200 postpartum was 71.4 and 54.3% for Groups 1 and 2, respectively (P>0.05).
      Results indicate that treatment of retained fetal membranes without intrauterine
      manipulation and treatment can be as effective as conventional treatment
      including detachment and local antibiotic treatment.

PMID- 12517397
TI  - Production of piglets using intracytoplasmic sperm injection (ICSI) with
      flowcytometrically sorted boar semen and artificially activated oocytes.
AB  - The purpose of the present study was to develop a protocol for the successful
      production of piglets employing intracytoplasmic sperm injection (ICSI) with
      flowcytometrically sexed spermatozoa and artificially activated porcine oocytes.
      In vitro matured oocytes were fertilized by ICSI using non-sorted frozen/thawed
      epididymal semen. Oocytes were either activated by CaCl(2), Ca(2+)-ionophore or
      electrical pulse. Activation and fertilization rates of sperm injected oocytes
      stimulated by CaCl(2)-injection were significantly higher than those without
      activation (70.4% versus 45.9%; 49.9% versus 33.2%, respectively; P<0.001).
      Activation rate of sham injected oocytes increased in parallel (11.2% versus
      26.3%, P<0.05), parthenogenetic development remained low (2.8% versus 8%). Co
      incubation in Ca(2+)-ionophore did not improve activation rates as compared to
      non-activated oocytes (44.8% versus 42.5%). Fertilization rate decreased as
      compared to non-treated sperm injected oocytes (36.8% versus 24.5%, P<0.05).
      Activation of oocytes with a single electrical pulse resulted in significantly
      higher activation rates in all groups of oocytes as compared to non-stimulated
      ones (sperm injected oocytes: 65.6% versus 43.1%, P<0.001; sham injected oocytes:
      48.5% versus 5.6%, P<0.001; control oocytes: 50.7% versus 0.0%, P<0.001).
      Fertilization rates (32.3% versus 48.2%) and parthenogenetic development (0.7%
      versus 38.9%, 0.0% versus 30.9%, P<0.001) increased significantly in parallel. In
      addition, in four replicates of flowcytometrically sorted Y-chromosome bearing
      spermatozoa were injected into in vivo matured oocytes, activated with 1.2 pl of
      a 30 mM CaCl(2) solution. On average 85.3 fertilized oocytes were transferred
      surgically into four recipients. Pregnancies delivered a total of 13 male
      piglets. These are the first piglets born from ICSI with sorted spermatozoa.

PMID- 12517398
TI  - Effects of oviductal and cumulus cells on in vitro fertilization and embryo
      development of porcine oocytes fertilized with epididymal spermatozoa.
AB  - This study was designed to evaluate the effects of adding porcine oviductal
      epithelial cell (POEC) monolayers before or during the fertilization of denuded
      or cumulus-enclosed oocytes, in terms of fertilization results and subsequent
      embryo development. The variables determined were: penetration rate, mean number
      of spermatozoa per oocyte, male pronucleus formation rate, monospermy rate,
      cleavage rate after 48 h of fertilization, blastocyst rate, and mean number of
      nuclei per blastocyst. We used cumulus-free and cumulus-enclosed oocytes
      preincubated or fertilized in the presence of POEC, once the purity in epithelial
      cells of these cultures had been assessed. All the experiments involved the use
      of frozen-thawed epididymal spermatozoa to avoid replicate variability. The POEC
      cultures prepared showed a high proportion of epithelial cells (over 95%).
      Preincubation of oocytes with POEC before fertilization showed no effects on the
      fertilization variables determined. In contrast, during IVF under our
      experimental conditions, these cells attached to the cumulus cells and their
      interaction had a significant effect on some of the fertilization variables
      analyzed. The presence of POEC and cumulus cells during IVF increased oocyte
      penetrability. Moreover, in the absence of POEC, cumulus cells resulted in a
      reduced monospermy rate. On subsequent embryo culture, a lower cleavage and
      blastocyst formation rate were recorded when the oocytes had been preincubated
      with POEC before IVF.

PMID- 12517399
TI  - In vitro maturation of bovine cumulus-oocyte complexes in undiluted follicular
      fluid: effect on nuclear maturation, pronucleus formation and embryo development.
AB  - Since resumption of meiosis and cytoplasmic maturation of bovine oocytes takes
      place in close association with follicular fluid, it would be logical to assume
      that this might be a perfect maturation medium. To test the hypothesis, abattoir
      derived cumulus-oocyte complexes (COCs) were in vitro matured in undiluted (i)
      mixed follicular fluid (FF) from 3 to 15 mm follicles from abattoir ovaries, (ii)
      preovulatory follicular fluid (POF) from the dominant follicle from a cyclic
      unstimulated heifer, (iii) preovulatory follicular fluid (OPU) from synchronised
      and superovulated heifers 60 h after prostaglandin and 20 h after GnRH treatment,
      and in (iv) TCM-199 with 5% serum. Subsequent to IVM, the COC were subjected to
      IVF and IVC, and embryo development was followed until the blastocyst stage at
      Day 8 after insemination. The MII rates in the TCM-199 (69%), POF (69%) and OPU
      (72%) groups were not different from each other but different from the FF (41%)
      group (P<0.05). In spite of the high MII rates, none of the follicular fluids
      supported embryo development: the FF, POF and OPU blastocyst rates were alike
      (3%, 3%, 2%) and different (P<0.05) from the rates in the TCM-199 (19%). During
      IVM in follicular fluids but not in TCM-199, the expanded cumulus masses became
      trapped in a coagulum. Although it could be prevented by the presence of heparin
      during IVM, it did not improve the blastocyst rates. In conclusion, undiluted
      preovulatory follicular fluids supported nuclear maturation but not further
      embryonic development as judged by the high MII and low blastocyst rates.

PMID- 12517400
TI  - Pregnancy rates in mares following hysteroscopic or transrectally-guided
      insemination with low sperm numbers at the utero-tubal papilla.
AB  - This study was conducted to evaluate two methods for insemination of a low number
      of sperm in the tip of the uterine horn, and to determine whether prebreeding
      intrauterine treatment with prostaglandin E(2) would improve pregnancy rates.
      Estrus was synchronized in 36 fertile Quarter Horse and Thoroughbred broodmares.
      When a dominant follicle >or=33 mm diameter was present, mares were treated with
      2500 units hCG intravenously and were assigned to one of four treatment groups
      for insemination with five million total sperm in 200 microl extender the next
      day as follows: (1) Group PGE-HYS (n=9): 0.25mg PGE(2) in 1 ml 0.9% NaCl solution
      infused into the tip of the uterine horn ipsilateral to the dominant follicle 2h
      prior to hysteroscopic-guided inseminate placement onto the oviductal papilla;
      (2) Group SAL-HYS (n=9): 1 ml 0.9% NaCl solution infused into the tip of the
      uterine horn ipsilateral to the dominant follicle 2h prior to hysteroscopic
      guided inseminate placement onto the oviductal papilla; (3) Group PGE-PIP (n=9):
      0.25mg PGE(2) in 1 ml 0.9% NaCl solution infused into the tip of the uterine horn
      ipsilateral to the dominant follicle 2h prior to transrectally-guided pipette
      placement of the inseminate into the tip of the uterine horn; and (4) Group SAL
      PIP (n=9): 1 ml 0.9% NaCl solution infused into the tip of the uterine horn
      ipsilateral to the dominant follicle 2h prior to transrectally-guided pipette
      placement of inseminate into the tip of the uterine horn. Mares in estrus were
      evaluated daily by transrectal ultrasonography to monitor follicular status and
      confirm ovulation. If mares had not ovulated within 2 days of insemination, the
      assigned treatment was repeated. Pregnancy status was evaluated by transrectal
      ultrasonography 12-14 days postovulation, and pregnancy rates were compared. No
      interaction between prebreeding treatment (SAL:PGE) and insemination protocol
      (HYS:PIP) on pregnancy rates occurred (P>0.10). Pregnancy rates did not differ
      between mares inseminated by HYS (12/18; 67%) or PIP (10/18; 56%) (P>0.10).
      Pregnancy rates did not differ between mares treated prior to breeding with PGE
      (11/18; 61%) or SAL (11/18; 61%) (P=1.00). In summary, satisfactory pregnancy
      rates were obtained when a low number of sperm were either placed directly onto
      the oviductal papilla using hysteroscopy or placed in the tip of the uterine horn
      using a transrectally-guided uterine pipette. Infusion of 0.25mg PGE(2) in the
      tip of the uterine horn 2h prior to insemination did not improve pregnancy rates.

PMID- 12517401
TI  - Purification and characterization of a protein tyrosine acid phosphatase from
      boar seminal vesicle glands.
AB  - A protein tyrosine phosphatase (PTPase) with acid phosphatase activity was
      purified (500-fold) from the fluid of boar seminal vesicles. Preparative
      purification was performed with a 3-step procedure, employing FPLC S-Sepharose
      Fast Flow, Mono Q and Superdex 75 column. Protein tyrosine acid phosphatase
      (PTAPase) was homogeneous by polyacrylamide gel electrophoresis (PAGE, SDS-PAGE).
      PTAPase is a glycoprotein which has a molecular weight of about 41-42 kDa. This
      enzyme was maximally active at pH 5.5, and its thermostability was less than 80
      degrees C. The K(m) value for p-nitrophenylphosphate, a specific synthetic
      substrate, was 0.87 x 10(-3)M, however, higher substrate specificity was shown
      when phosphotyrosine (K(m)=0.37 x 10(-3)M) and protein fragments, such as gastrin
      (K(m)=0.0032 x 10(-3)M) and hirudin (K(m)=0.0075 x 10(-3)M), were used as
      substrates. Activity of PTAPase was inhibited by dephostatin, molybdate and
      orthovanadate by 100, 95 and 70%, respectively, when phosphotyrosine was used as
      the substrate. Immunofluorescence study has shown that the seminal vesicles are
      the only source of PTAPase in boar seminal plasma.

PMID- 12517402
TI  - Behavioural development in the neonatal lamb: effect of maternal and birth
      related factors.
AB  - The survival of the neonate relies on the integrated expression of appropriate
      behaviours from both the mother and young. In precocious species, like the sheep,
      the speed with which the lamb stands and seeks the udder is related to lamb
      survival. In this study the effects of birth difficulty, lamb birth weight, ewe
      loss or gain in backfat from conception to delivery, ewe parity, litter size, and
      lamb sex on neonatal lamb behavioural development were investigated in over 500
      lambs of two breeds (Scottish Blackface and Suffolk). Lambs that required
      assistance to be delivered were significantly slower to perform all neonatal
      behaviours than unassisted lambs (P<0.001), and were less active over the first 3
      days after delivery (P<0.05). There were no effects of lamb birthweight that were
      not accounted for by the increased likelihood of requiring assistance in heavier
      birth weight lambs. Ewes that mobilised less body fat during their pregnancy
      produced lambs that stood and sucked quickly (P<0.001), and were more active over
      the first 3 days of life. Lambs born to first parity ewes were slower to stand
      and suck than lambs born to experienced ewes (P<0.001). There was an improvement
      in time taken by lambs to stand, seek the udder and to suck with each increase in
      ewe parity. Litter size had an additional retarding influence on the behaviour of
      multiple-born lambs that could not be accounted for by birthweight. In the
      Suffolk breed male lambs were slower to stand and suck than female lambs, this
      effect was not seen in Blackface lambs. These data demonstrate that lambs that
      require assistance at birth, even if they survive the birth process, lambs born
      to ewes that lose a lot of condition over pregnancy or first parity ewes, triplet
      lambs and, at least in some breeds, male lambs are slower to progress through the
      sequence of neonatal behaviours. These lambs are, therefore, at greater risk of
      not surviving to weaning.

PMID- 12517403
TI  - Studies of the pathogenesis of bovine pestivirus-induced ovarian dysfunction in
      superovulated dairy cattle.
AB  - Two experiments (Experiment I, n=12 Holstein-Friesian heifers; Experiment II, n=8
      Jersey cows) were conducted to investigate the pathogenesis of bovine pestivirus
      induced ovarian dysfunction in cattle. In both experiments the cattle were
      superovulated with twice daily injections of a porcine pituitary extract
      preparation of follicle stimulating hormone (FSH-P), for 4 days commencing on Day
      10+/-2 after a presynchronised oestrus. The heifers received a total dose of 30
      mg and the cows 32 mg of FSH-P. Prostaglandin F(2alpha) (PGF(2alpha)) was
      administered 48 h after commencement of superovulation and all cattle were
      artificially inseminated (AI) between 48 and 66h after PGF(2alpha) treatment. In
      both experiments bovine pestivirus seronegative cattle (Experiment I, n=6;
      Experiment II, n=4) were inoculated intranasally with an Australian strain of non
      cytopathogenic bovine pestivirus (bovine viral diarrhoea virus Type 1) 9 days
      prior to AI. Bovine pestivirus infection was confirmed by seroconversion and/or
      virus isolation in all of the inoculated cattle, consistent with a viremia
      occurring approximately between Day 5 prior to AI and the day of AI. Ovarian
      function was monitored in both experiments by daily transrectal ultrasonography
      and strategic blood sampling to determine progesterone, oestradiol-17beta,
      luteinising hormone (LH) and cortisol profiles. Non-surgical ova/embryo recovery
      was performed on Day 7 after AI. In Experiment II half the cattle were
      slaughtered on Day 2 and the remainder on Day 8 after AI, and the ovaries
      submitted for gross and histopathological examination including
      immunohistochemistry to demonstrate the presence of bovine pestivirus antigen. In
      both studies, comparisons were made between infected and confirmed uninfected
      (control) animals. Overall the bovine pestivirus infected cattle had
      significantly lower (P<0.05) ova/embryo recovery rates compared to the control
      cattle. There was evidence of either an absence (partial or complete) of a
      preovulatory LH surge or delay in timing of the LH peak in the majority (90%) of
      infected heifers and cows, and histologically, there was evidence of non
      suppurative oophoritis with necrosis of granulosa cells and the oocyte in
      follicles from the infected cows. By contrast only 20% of the control heifers and
      cows had evidence of absence of a pre-ovulatory LH surge. These experiments
      collectively demonstrate that bovine pestivirus infection during the period of
      final growth of preovulatory follicles may result in varying degrees of necrosis
      of the granulosa cells with subsequent negative effects on oestradiol-17beta
      secretion which in turn negatively affects the magnitude and/or timing of the
      preovulatory LH surge.

PMID- 12517404
TI  - Health and Safety Advisory Committee (HASAC) of the International Embryo Transfer
      Society (IETS) has managed critical challenges for two decades.
AB  - The International Embryo Transfer Society (IETS) was founded in 1974. Early
      members used the society as a forum for the exchange of scientific and technical
      information relevant to a newly emerging embryo transfer industry. The impact
      that embryo transfer could have on the international trade of livestock genetics
      was clear by 1982, so the IETS commissioned the Import/Export Committee. The
      initial challenge for this Committee was to deal with concerns about disease
      transmission via embryo transfer. Many of the early concerns have been dispelled,
      but at the time they threatened the continued development of a fledgling
      industry. Over the past two decades, many new critical challenges have been met
      and managed by this Committee, which was recently renamed the Health and Safety
      Advisory Committee (HASAC). Assessing risks of animal disease transmission via
      reproductive technologies and establishing protocols for managing these risks are
      still major issues for HASAC. However, additional concerns have developed as
      views of the society changed and as novel applications of biotechnology in farm
      animals were identified. This paper is intended to chronicle some of the major
      changes and challenges that were managed by members of the HASAC and its
      Subcommittees from the early years of embryo transfer to the current millennium
      with technological advances in molecular biology.

PMID- 12517406
TI  - Evolution of mutational robustness.
AB  - We review recent advances in the understanding of the mutation-selection balance
      of asexual replicators. For over 30 years, population geneticists thought that an
      expression derived by Kimura and Maruyama in 1966 fully solved this problem.
      However, Kimura and Maruyama's result is only correct in the absence of neutral
      mutations. The inclusion of neutral mutations leads to a wealth of interesting
      new effects, and, in particular, to a selective pressure to evolve robustness
      against mutations. We cover recent literature on the population dynamics of
      asexual replicators on networks of neutral genotypes, on the outcompetition of
      fast replicators by slower ones with better mutational support, and on the
      probability of fixation at high mutation rates. We discuss empirical evidence for
      the evolution of mutational robustness, and speculate on its relevance for higher
      organisms.

PMID- 12517407
TI  - Clonal expansions of mitochondrial genomes: implications for in vivo mutational
      spectra.
AB  - It is often assumed mutant frequencies, as measured in a DNA sample, faithfully
      represent basic mutation rates associated with these mutations. This paradigm was
      extremely helpful for in vitro studies of the mechanisms of mutagenesis/repair
      and causes of mutations. However, in vivo, mutant fractions appear to vary
      dramatically and randomly from sample to sample. It's unlikely that basic
      mutational rates vary so much. Such variations are probably caused by clonal
      expansions of mutants within tissue. Whether a particular tissue sample includes
      an expansion or not, is a matter of chance, which explains the observed random
      fluctuations of mutant fractions. Well-known examples of clonal expansions
      involve pathological conditions such as cancer or mitochondrial disease. It is
      less appreciated that even in normal tissue, expansions of somatic mutants create
      local deviations from the "expected" mutant frequencies. The sizes of clonal
      expansions appear to span a wide range and thus, may affect samples of various
      sizes, from individual cells to individuals. In conclusion, human body appears to
      be a sort of a "gambling ground" for clonally expanding mutants. We speculate
      that expansion of early mutants rather than de novo mutation at old age may be
      the major source of at least some aging-specific mutants in our bodies.

PMID- 12517408
TI  - Mitotic recombination is an important mutational event following oxidative
      damage.
AB  - The mutagenic effects of hydrogen peroxide (H(2)O(2)), a source of reactive
      oxygen species (ROS) have been determined in human lymphocytes. T-lymphocytes
      mutated at the autosomal HLA-A locus on chromosome 6 have been clonally isolated
      (N = 2097 clones) and the molecular basis of each clonal mutation characterised
      as due to intragenic, deletion or mitotic recombination mutation. H(2)O(2) caused
      a dose dependent increase in mutation frequency. There was no significant
      increase in the frequency of intragenic mutations. Mitotic recombination (MR) was
      responsible for 87% of the increase in mutation frequency induced by H(2)O(2) and
      gene deletion was responsible for 13%. MR results in loss of heterozygosity (LOH)
      distal to the recombination site. It is known that LOH is important in the
      initiation and progression of cancer. These results suggest that the biologically
      important consequence of some ROS may be LOH as a by-product of recombination
      repair. They also suggest that if our observations apply to ROS generally, then
      many of the mutations which accumulate with ageing or which are observed in
      cancer may be due to factors other than ROS.

PMID- 12517409
TI  - Mismatch repair in the antimutator Escherichia coli mud.
AB  - Antimutators are genetic mutants that produce mutations at reduced rates compared
      to the wild type strain. They are interesting because they may provide insights
      into the mechanisms by which spontaneous mutations occur. We have investigated a
      reported antimutator strain of Escherichia coli termed mud for its possible
      mechanism. The mud strain exhibits a decrease in both spontaneous mutagenesis and
      mutability with alkylated agents and base analogs. These types of DNA lesions are
      known to be the substrates for the E. coli methyl-directed mismatch repair
      encoded by the mutHLSU system. We investigated whether the putative antimutator
      effect results from the increased expression or activity of the mutHLSU system.
      To directly measure the mismatch repair capacity of mud cells, we have
      transfected them with phage lambda heteroduplexes and scored the fraction of
      mixed (unrepaired) infective centers. This transfection system has been used
      routinely to assay mismatch repair capacity in E. coli and other organisms. No
      difference between mud and wild type cells is observed. From the results of the
      experiments we conclude that the reported antimutator effect of mud does not
      result from enhanced mismatch repair capacity. This conclusion is consistent with
      recently published evidence that the mud effect does not represent a real
      antimutator effect, but is an artifact due to impaired growth of mud cells under
      certain selective conditions.

PMID- 12517410
TI  - Induction of SOS response, cellular efflux and oxidative stress response genes by
      chlorambucil in DNA repair-deficient Escherichia coli cells (ada, ogt and mutS).
AB  - Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer
      agent and as an immunosuppressant. It is known to be mutagenic, teratogenic and
      carcinogenic. The cellular actions of CLB have remained poorly investigated. It
      is very likely that DNA damage and its repair are the key elements determining
      the destiny of CLB-exposed cells. We investigated the role of two specific DNA
      repair pathways involved in CLB-induced mutagenicity and gene expression changes
      by using Escherichia coli strains lacking either (i) two DNA methyltransferase
      functions (O(6)-methylguanine-DNA methyltransferase I (ada) and II (ogt)), or
      (ii) mismatch repair (MutS (mutS)). Mutagenicity was determined as the
      development of ciproxin and rifampicin resistance and the gene expression changes
      were assessed using expression profiling of all E. coli 4290 open reading frames
      (ORFs) by cDNA array. Chlorambucil-induced mutants in mutS cells, implying the
      importance of mismatch repair in preventing CLB-induced mutations. It also
      induced mutants in the ada, ogt strain, but to a lesser extent than in the wild
      type strain. The simultaneous upregulation of several genes of the SOS response,
      cellular efflux and oxidative stress response, was demonstrated in both of the
      DNA repair-deficient strains but not in the wild-type cells. These and our
      previous results show that single-gene knock-out cells use specific gene
      regulation strategies to avoid mutations and cell death induced by agents such as
      chlorambucil.

PMID- 12517411
TI  - DNA damage by carbonyl stress in human skin cells.
AB  - Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress
      originating from endogenous chemical processes such as lipid peroxidation and
      glycation. Skin deterioration as observed in photoaging and diabetes has been
      linked to accumulative protein damage from glycation, but the effects of carbonyl
      stress on skin cell genomic integrity are ill defined. In this study, the
      genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3
      fibroblasts were assessed. Administration of the alpha-dicarbonyl compounds
      glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell
      proliferation, led to intra-cellular protein glycation as evidenced by the
      accumulation of N(epsilon)-(carboxymethyl)-L-lysine (CML) in histones, and caused
      extensive DNA strand cleavage as assessed by the comet assay. These effects were
      prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal
      and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks
      while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by
      pronounced nuclear condensation and total suppression of comet formation.
      Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro
      and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed
      by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of
      cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is
      followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of
      RCS in cultured skin cells and its suppression by a carbonyl scavenger as
      described in this study have implications for skin damage and carcinogenesis and
      its prevention by agents selective for carbonyl stress.

PMID- 12517412
TI  - Coffee and its chemopreventive components Kahweol and Cafestol increase the
      activity of O6-methylguanine-DNA methyltransferase in rat liver--comparison with
      phase II xenobiotic metabolism.
AB  - A lower rate of colon cancer was observed in consumers of coffee with a high
      content of the diterpenes Kahweol and Cafestol (K/C). In animal models, K/C have
      been found to protect against the mutagenic/carcinogenic effects of compounds
      such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), aflatoxin B1, and
      7,12-dimethylbenz[a]anthracene. Thus far, such chemoprotection by K/C has been
      attributed to modifications of xenobiotic metabolism, e.g. enhanced
      detoxification by UDP-glucuronosyltransferase (UDPGT) and/or glutathione
      transferase (GST). In the present study, we investigated the potential of several
      coffee-related treatments (K/C [1:1], Cafestol-alone, Turkish coffee) to modify
      the expression level of the DNA repair protein O(6)-methylguanine-DNA
      methyltransferase (MGMT) which is involved in the reversal of the precarcinogenic
      DNA damage O(6)-alkylguanine induced by alkylating agents. The results show that,
      in the male F344 rat, K/C and Cafestol increase hepatic MGMT in a dose-dependent
      manner up to a maximum of 2.6-fold at 0.122% K/C in the feed. Turkish coffee led
      to enhancements of up to 16%, the more moderate increase being associated with
      the lower estimated K/C intake through the beverage. In the livers of the rats
      receiving Turkish coffee, we also found 10-30% increases in several GST-related
      parameters (overall GST, GST-pi, glutathione, gamma-glutamylcysteine-synthetase)
      and a two-fold increase in UDPGT activity. Dose-response studies with K/C
      revealed that MGMT increased in parallel with three of the four GST-related
      parameters whereas the dose-response curves of UDPGT and of GST-pi activity
      displayed a steeper slope. Increased expression level of MGMT may extend the
      antimutagenic/anticarcinogenic potential of coffee components to protection
      against DNA alkylating agents.

PMID- 12517413
TI  - Activities of wildtype and mutant p53 in suppression of homologous recombination
      as measured by a retroviral vector system.
AB  - DNA repair of double strand breaks, interstrand DNA cross-links, and other types
      of DNA damage utilizes the processes of homologous recombination and non
      homologous end joining to repair the damage. Aberrant homologous recombination is
      likely to be responsible for a significant fraction of chromosomal deletions,
      duplications, and translocations that are observed in cancer cells. To facilitate
      measurement of homologous recombination frequencies in normal cells, mutant
      cells, and cancer cells, we have developed a high titer retroviral vector
      containing tandem repeats of mutant versions of a GFP-Zeocin resistance fusion
      gene and an intact neomycin resistance marker. Recombination between the tandem
      repeats regenerates a functional GFP-Zeo(R) marker that can be easily scored.
      This retroviral vector was used to assess homologous recombination frequencies in
      human cancer cells and rodent fibroblasts with differing dosages of wild type or
      mutant p53. Absence of wild type p53 stimulated spontaneous and ionizing
      radiation-induced homologous recombination, confirming previous studies.
      Moreover, p53(+/-) mouse fibroblasts show elevated levels of homologous
      recombination compared to their p53(+/+) counterparts following retroviral vector
      infection, indicating that p53 is haploinsufficient for suppression of homologous
      recombination. Transfection of vector-containing p53 null Saos-2 cells with
      various human cancer-associated p53 mutants revealed that these altered p53
      proteins retain some recombination suppression function despite being totally
      inactive for transcriptional transactivation. The retroviral vector utilized in
      these studies may be useful in performing recombination assays on a wide array of
      cell types, including those not readily transfected by normal vectors.

PMID- 12517414
TI  - Repair of DNA alkylation products formed in 9L cell lines treated with 1-(2
      chloroethyl)-1-nitrosourea.
AB  - The purpose of this study has been to measure the formation and repair of
      individual DNA alkylation products in 9L, 9L-2 and BTRC-19 cell lines after
      treatment with 1-(2-chloroethyl)-1-nitrosourea (CNU). The levels of seven DNA
      adducts N7-(2-hydroxyethyl)-guanine, N7-(2-chloroethyl)-guanine; 1,2-(diguan-7
      yl)-ethane, N1-(2-hydroxyethyl)-2-deoxyguanosine, 1-(N1-2-deoxyguanosinyl), 2-(N3
      2-deoxycytidyl)-ethane, O(6)-(2-hydroxyethyl)-2-deoxyguanosine and
      phosphotriesters were separated by HPLC and quantified by liquid scintillation
      counting. The levels of N7-(2-hydroxyethyl)-guanine, N7-(2-chloroethyl)-guanine;
      O(6)-(2-hydroxyethyl)-2-deoxyguanosine and phosphotriesters were not
      significantly different in the three glioma lines. Furthermore, comparison of the
      levels of these products in treated cells with the levels formed in purified DNA
      suggest that they were not actively repaired over the 6h interval. The levels of
      1,2-(diguan-7-yl)-ethane and N1-(2-hydroxyethyl)-2-deoxyguanosine were reduced in
      9L-2 and significantly reduced in BTRC-19 (P = 0.003) compared to 9L. Analysis of
      the data suggests that the reduction in the level of N1-(2-hydroxyethyl)-2
      deoxyguanosine was due to repair of its precursor O(6)-ClEtdG by O(6)
      alkylguanine-DNA-alkyltransferase (AGT). The level of the crosslinked product 1
      (N1-2-deoxyguanosinyl), 2-(N3-2-deoxycytidyl)-ethane was significantly reduced (P
      < 0.001) in both 9L-2 and BTRC-19 as compared to 9L. Reduction in the level of 1
      (N1-2-deoxyguanosinyl), 2-(N3-2-deoxycytidyl)-ethane in 9L-2 and BTRC-19 are
      consistent with repair of the precursor alkylation product O(6)-ClEtdG by AGT.
      This study demonstrates that there are very significant differences in the rates
      of removal of individual DNA adducts formed by CNU treatment of the glioma cell
      lines.

PMID- 12517415
TI  - In vitro characterization of a human calcitonin receptor gene polymorphism.
AB  - Calcitonin is a 32 amino acid peptide hormone that inhibits bone resorption by
      stimulating calcitonin receptors (CTR) located on the surfaces of osteoclasts. A
      polymorphism at nucleotide 1340 of the human calcitonin receptor gene (CALCR)
      lies within the coding region and has the potential to change the amino acid at
      codon 447 from leucine to proline. In the present study, we scanned the coding
      region, portions of the 5'-flanking and 3'-flanking sequences, and the intron
      exon boundaries of the human CALCR gene for additional polymorphisms, and
      determined the frequency of the codon 447 polymorphism in several ethnic groups.
      Because a leucine to proline change has the potential for significant structural
      alteration, receptor genes encoding either leucine or proline at residue 447 were
      transiently expressed in COS-7 cells to determine the binding and functional
      consequences of this polymorphism. Our complete polymorphism scan of the CALCR
      gene identified 11 polymorphic sites in the gene and confirmed the presence of
      the previously identified nucleotide T1340C (codon 447) polymorphism. Ten of the
      11 polymorphisms were single nucleotide polymorphisms (SNPs). For the codon 447
      polymorphism, the prevalence of the TT genotype (leucine) was 59% in Caucasians,
      27% in African-Americans, 0% in Asians, and 20% in Hispanics. The presence of
      this SNP appears to have no statistically significant difference with the
      receptor's ability to bind calcitonin or signal when activated with the hormone.

PMID- 12517416
TI  - Mutagenicity of the oral carcinogen 4-nitroquinoline-1-oxide in cultured BigBlue
      rat tongue epithelial cells and fibroblasts.
AB  - Environmental carcinogen exposures contribute to the development of oral cancer
      and improved test systems for the analysis of such carcinogens are needed. We
      have previously isolated and characterized an epithelial cell line from the
      tongue of a BigBlue rat. Now, we have established an immortalized fibroblast cell
      line from the same organ. We exposed these cells to 4-nitroquinoline-1-oxide
      (NQO), a well-known experimental oral carcinogen in the rat and other species,
      and measured its cytotoxic and genotoxic (cII transgene mutagenesis) effects.
      Both cell lines were very sensitive to NQO toxicity and showed dose-dependent
      mutant frequency responses. At the highest NQO dose tested, 70 ng/ml, the mutant
      frequency was elevated more than eight-fold above background for the epithelial
      cells and more than 25-fold for the fibroblast cells. We examined cellular
      parameters which could affect glutathione-dependent detoxication of mutagens.
      Glutathione (GSH) contents of the two cell lines were similar. Glutathione
      transferase (GST) activities were measured with several substrates and were
      generally higher in the epithelial cells. Although multiple biochemical and
      biological characteristics of individual cell lines are likely to determine
      responses to mutagens, the greater sensitivity of the fibroblast cells to NQO
      mutagenicity is in accord with the lower GST activity and the lower DNA content
      of these cells. These new cell lines are suitable for in vitro testing of
      chemicals as possible oral mutagens and for studies of their biochemical
      mechanisms of action.

PMID- 12517417
TI  - Mannose-binding lectin gene polymorphisms and hepatitis B virus infection in
      Vietnamese patients.
AB  - Mannose-binding lectin (MBL) is a constituent of the human innate immune system
      which may play an important role in combating a variety of infectious diseases.
      We investigated the distribution of MBL gene mutations in a Vietnamese
      population, using polymerase chain reaction and DNA sequence analysis, and sought
      associations with the outcome of hepatitis B virus (HBV) infection. For this
      purpose we used samples from a total of 123 patients with confirmed, well-defined
      HBV infections, representing a full spectrum of clinical presentation from acute
      to chronic to malignant states, as well as from 112 healthy controls. The only
      MBL gene mutation found in this population, that at codon 54 of exon 1, was
      present at an overall frequency of 0.12, with a trend towards a higher frequency
      in the HBV-infected group compared with controls (0.15 versus 0.08, P = 0.079).
      Within the HBV-infected group there was a non-significant trend towards higher
      viral loads in those with this mutation, accompanied by significantly higher
      serum transaminase levels in the same individuals. Segregation according to
      clinical presentation showed that the mutation was present at a significantly
      higher frequency in the group with acute hepatitis B (AHB) compared with the
      healthy control group (0.25 versus 0.08, P = 0.01), and was associated with
      higher serum transaminase levels. Our results indicate that a mutation of the MBL
      gene might influence the clinical outcome of HBV infection in Vietnamese
      patients.

PMID- 12517418
TI  - Effect of recombinant interferon-alpha on streptonigrin-induced chromosome
      aberrations and sister-chromatid exchanges in hamster cells.
AB  - The effect of recombinant interferon-alpha-2a (rIFN-alpha-2a) on the induction of
      chromosomal aberrations (CAs) and sister-chromatid exchanges (SCEs) by the
      radiomimetic antibiotic streptonigrin (SN, 250 ng/ml, 20 min, 37 degrees C) in
      Chinese hamster ovary (CHO) cells was investigated. Recombinant IFN-alpha-2a
      (4500-45,000 IU/ml) was added to the cell cultures 30 min before SN and left in
      the culture medium until the end of SN treatment or until cell harvesting. A
      statistically significant increase in the frequency of CAs and SCEs was observed
      following treatment with SN (P < 0.05), whereas treatments with rIFN-alpha-2a
      alone did not produce any significant increase of CAs and SCEs over control
      values. Low rIFN-alpha-2a doses produced a reduction in the frequency of CAs and
      an increase in the yield of SCEs induced by SN, while high doses of the cytokine
      caused an increase in the yield of CAs and a reduction in the frequency of SCEs
      induced by the antibiotic. In addition, rIFN-alpha-2a caused a marked inhibition
      (around 50%) on the yield of SN-induced chromatid-type aberrations in the G(2)
      phase of the cell cycle. It is suggested that the inhibitory effect of rIFN-alpha
      2a on the SN-induced chromosome damage is due to the stimulation of DNA synthesis
      and repair by the cytokine. On the other hand, our results give further support
      to our previous hypothesis that the induction of CAs and SCEs by SN is based on
      different mechanisms.

PMID- 12517419
TI  - Bcl-2 reduces mutant rates in a transgenic lacZ reporter gene in mouse pre-B
      lymphocytes.
AB  - To assess mutagenesis during early B-lymphocyte development in vitro, progenitor
      B cells (pre-B cells) were obtained from fetal livers of BALB/c mice and DBA/2N
      mice that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter
      gene for the determination of mutant frequencies (MFs). Differentiation-arrested
      pre-B cells demonstrated a marked dose-dependent increase in lacZ mutant levels
      after exposure to gamma-irradiation with a peak MF of 250 x 10(-5) at 2.5 Gy.
      Without genotoxic treatment, pre-B cells undergoing spontaneous differentiation
      into surface IgM expressing immature B cells exhibited lacZ mutant levels of up
      to 95 x 10(-5). The mutational pattern was dominated in both experiments by
      illegitimate recombination mutations of lacZ, not point mutations. Likewise, in
      both experiments, the enforced expression of Bcl-2 resulted in a striking
      reduction of lacZ mutations. These findings indicated that mouse pre-B cells are
      prone to accumulate induced and self-inflicted mutations, particularly
      recombinations. Additionally, our studies revealed a heretofore unknown role of
      Bcl-2 in inhibiting mutagenesis during early B-cell development in mice.

PMID- 12517420
TI  - In vivo deamination of cytosine-containing cyclobutane pyrimidine dimers in E.
      coli: a feasible part of UV-mutagenesis.
AB  - We have estimated in vivo deamination rates for cytosines in cyclobutane
      pyrimidine dimers (CPD or PyPy) in UV-irradiated E. coli deficient in uracil DNA
      glycosylase. The protocol consisted of UV-irradiation, holding in buffer to allow
      for deamination of cytosines in CPDs and photoreversal (PR) to establish uracils
      where cytosines in CPD deaminated. The deamination rate at TC photoproducts
      targeting glutamine tRNA suppressor mutations was estimated from the increase in
      the mutation frequency after PR (MF(PR)) that developed as UV-irradiated cells
      were held before PR. Evidence suggested that an earlier study with this protocol
      under-estimated the deamination rate at sites producing the same mutations in an
      E. coli B/r strain. With a K12 strain, where the targeting apparently is
      principally by CPD and not (6-4) photoproducts, a larger rate of k = 0.0091 min(
      1) at 42 degrees C resulted. The dark assay for MF also increased significantly
      with time for deamination consistent with a model for efficient mutation by
      translesion synthesis at uracil-containing CPD. In addition, we used a strain
      constructed by Cupples and Miller in which beta-galactosidase was inactive
      because -GGG- was at codon 461 and would revert to Lac(+) only when replaced by 
      GAG- or -GAA- for glutamate. CC photoproducts at this target site in the opposite
      DNA strand could reveal effects of first and second deaminations in the same CPD.
      MF(PR) for Lac(+) mutations increased and then decreased as a function of
      deamination time (at six temperatures 36-48 degrees C). Fitting an approximate
      model equation that distinguished two different deamination rates to these data
      suggested a first deamination producing Lac(+) at a rate about eight-fold less
      than a second deamination restoring the Lac(-) phenotype. We conclude that
      deamination, changing a cytosine-containing CPD to a uracil-containing CPD, could
      be an integral part of UV-induced C-to-T mutations.

PMID- 12517421
TI  - Tolerance of five species of tropical marine mussels to continuous chlorination.
AB  - The paper examines the relative lethal and sublethal response of five important
      tropical marine mussels (Perna viridis, Perna perna, Brachidontes striatulus,
      Brachidontes variabilis and Modiolus philippinarum) to different chlorine
      concentrations varying from 0.25 to 15 mg l(-1). The mussels were observed to co
      exist in the cooling water circuits of a coastal power station that adopted
      intermittent chlorination as a fouling control technique. The five mussel species
      showed, in response to chlorination, 100% mortality at significantly different
      exposure times, indicating significant species-specific variability in chlorine
      tolerance. For example, at 1 mg l(-1) residual chlorine, B. variabilis and P.
      viridis took 288 and 816 h, respectively, to achieve 100% mortality. The time
      taken for 100% mortality decreased with increasing chlorine residual
      concentration. The effect of mussel size (= mussel age) of P. viridis, P. perna,
      B. striatulus and M. philippinarum on mortality was significant between 1 and 5
      mg l(-1) residual chlorine, with larger mussels showing greater resistance than
      smaller ones. All mussel species showed progressive reduction in physiological
      activities when chlorine residuals were increased from 0 to 1 mg l(-1). However,
      species-specific differences in the relative rate of physiological activities
      were observed. Accordingly, relative reduction in physiological activities in
      response to chlorination was the lowest in P. viridis and the highest in B.
      variabilis. The data clearly indicate significant differences in the lethal and
      sublethal responses of the five mussel species to chlorination. The results,
      therefore, suggest that for effective fouling control, chlorine treatment against
      mussels has to be employed judiciously, depending on the mussel species involved.

PMID- 12517422
TI  - The effects of sewage discharge on water quality and phytoplankton of Hawai'ian
      coastal waters.
AB  - The effects of sewage discharge on algal populations and the quality of Hawai'ian
      coastal waters were investigated. Two outfalls were studied. One discharges
      primary treated sewage and the other discharges secondary treated sewage but are
      otherwise similar. This enabled comparisons of the effects of these different
      levels of treatment on the water quality and algal productivity of receiving
      waters. Plumes were followed and repeatedly sampled in a time-series manner.
      Rhodamine dye was used as a conservative tracer to compare the dilution behavior
      of the plume constituents MRP, NO(3)+NO(2), NH(4), Silicate, TDP, TDN, total
      bacteria, PC, and PN. Rates of initial dilution ranged from two to almost three
      orders of magnitude, and were in reasonable agreement with engineering model
      predictions. Dilution of plume constituents approximated that of Rhodamine until
      background concentrations were reached, typically within 10 min of discharge. Chl
      a concentrations did not increase through time in the primary sewage plume but
      did increase up to 30% in the secondary sewage plume. However, rates of far-field
      dilution were so rapid that the increase could not have been due to algal growth.
      The increase was attributed to the plume mixing with a water mass whose relative
      chl a concentrations were greater. Rates of secondary dilution ranged from 2 to 3
      orders of magnitude resulting in total dilutions of 10(5)-10(6) within 3 h of
      discharge. These rates of secondary dilution were much greater than model
      predictions. From a nutrient standpoint, secondary treatment exhibited no
      advantages over primary treatment because dilutions were so rapid.

PMID- 12517423
TI  - The influence of fish cage aquaculture on pelagic carbon flow and water chemistry
      in tidally dominated mangrove estuaries of peninsular Malaysia.
AB  - The impact of floating net cages culturing the seabass, Lates calcarifer, on
      planktonic processes and water chemistry in two heavily used mangrove estuaries
      in Malaysia was examined. Concentrations of dissolved inorganic and particulate
      nutrients were usually greater in cage vs. adjacent (approximately 100 m) non
      cage waters, although most variability in water-column chemistry related to water
      depth and tides. There were few consistent differences in plankton abundance,
      production or respiration between cage and non-cage sites. Rates of primary
      production were low compared with rates of pelagic mineralization reflecting high
      suspended loads coupled with large inputs of organic matter from mangrove
      forests, fishing villages, fish cages, pig farms and other industries within the
      catchment. Our preliminary sampling did not reveal any large-scale eutrophication
      due to the cages. A crude estimate of the contribution of fish cage inputs to the
      estuaries shows that fish cages contribute only approximately 2% of C but greater
      percentages of N (32-36%) and P (83-99%) to these waters relative to
      phytoplankton and mangrove inputs. Isolating and detecting impacts of cage
      culture in such heavily used waterways--a situation typical of most mangrove
      estuaries in Southeast Asia--are constrained by a background of large, highly
      variable fluxes of organic material derived from extensive mangrove forests and
      other human activities.

PMID- 12517424
TI  - Input of atmospheric lead to marine sediments in a south-east Pacific coastal
      area (approximately 36 degrees S).
AB  - Atmospheric input of Pb to coastal sediments in the south-east Pacific
      (approximately 36 degrees S) was estimated using: (1) a salt marsh (non-local
      emission sources) as a natural collector of atmospheric fluxes and (2) Pb
      concentrations in rain and air samples, both considered to be representative of
      the atmospheric input in the study area. A radioisotopic geochronology technique
      ((210)Pb) was used to estimate the total Pb atmospheric supply to the sediments.
      The results show that atmospheric input to Concepcion Bay accounts for 13-68% of
      Pb in near shore sediments, evaluated through salt marsh and rain, both showing
      comparable results. Consequently, there are other relevant Pb sources to explain
      the higher concentrations in this area. Sediments in the shelf are subject to
      important influence of upwelling waters, estimated by Salamanca [Sources and
      sinks of (210)Pb in Concepcion Bay, Chile (1993) PhD thesis, Marine Science
      Research Center, State University of New York at Stony Brook, USA] using (210)Pb.
      The atmospheric input, however, is mainly responsible for the total Pb input,
      since the salt marsh (natural atmospheric collector) shows similar Pb(xs)
      inventories than the shelf, corresponding to a regional-scale Pb emissions.

PMID- 12517426
TI  - Going gently into flight: analyzing noncovalent interactions by mass
      spectrometry.

PMID- 12517427
TI  - Synthesis and evaluation of new 5-fluorouracil antitumor cell differentiating
      derivatives.
AB  - Three new antitumour drugs containing two 5-fluorouracil moieties at both ends of
      the structure and a two amide bond linker were synthesized. Appropriated bis
      acetal were reacted with two equivalents of 5-FU to afford the desired compounds.
      These drugs were evaluated for their ability to induce myogenic maturation in
      vitro on human rhabdomyosarcoma cells in an experimental model. Compounds 5 and 6
      induced morphological and phenotypical differentiation in rhabdomyosarcoma cells
      at 4.5 and 3.5 microM, respectively. These new cell differentiating agents could
      be used as an alternative to selective destruction of undifferentiated cells. A
      potential role of the differentiation therapy as an alternative approach to the
      treatment of rhabdomyosarcomas is suggested.

PMID- 12517428
TI  - New nitrogen mustards structurally related to (L)-carnitine.
AB  - Enantiopure nitrogen mustards which mimic (L)-carnitine framework are prepared by
      a multi-step synthesis from the (R)-di-tert-butyl malate and their antitumor
      properties evaluated.

PMID- 12517429
TI  - Synthesis, characterization and biological evaluation of 7 alpha
      perfluoroalkylestradiol derivatives.
AB  - Linkage of a long CH(2 )side chain ('spacer') onto C-7 alpha of estradiol-17 beta
      (E(2)) does not abrogate the binding affinity of this hormone for its receptor.
      Our purpose was to assess whether the linkage of a CF(2 )side chain, which is
      more bulky and rigid, could also be accommodated by the estrogen receptor (ER).
      We describe here the synthesis of 7 alpha-perfluorohexylestradiol 7 by
      perfluoroalkylation of a key silylenolether 2 with FITS-6 (perfluorohexyl
      phenyliodoniurn trifluoromethanesulfonate). 7 alpha-Trifluoromethylestradiol 10a
      was prepared as a fluorinated control compound by UV-light induced
      trifluoromethylation of 2 with Umemoto reagent (S
      trifluoromethyldibenzo[b,d]thiophenium trifluoromethanesulfonate). Endocrine
      properties of these two E(2 )derivatives were tested on the MCF-7 breast cancer
      cell line. Our data reveal that rigidity of the side chain of 7 affected the
      association of its hormone moiety with the ER to the same extent as a long alkyl
      side chain. Rigidity also failed to abrogate estrogenicity, as demonstrated by
      the ability of 7 to enhance ERE-dependent transcription and cell growth. Compound
      retained the capacity of inducing down regulation of the receptor. Interestingly,
      no evidence of antiestrogenicity was recorded since this compound behaved like a
      weak estrogen, exerting a mitogenic effect at high concentration. Of note,
      control 10a displayed a higher binding affinity than 7 for ER and consequently
      acted like the latter, albeit with a higher efficiency. Selection of appropriate
      residues to be linked at the end of a long 7 alpha alkyl side chain is known to
      be essential for generating strong antiestrogenicity. One may hope that such a
      property may also hold for perfluorinated chains to produce antiestrogens with
      strong metabolic stability.

PMID- 12517430
TI  - 2-Phenylimidazo[2,1-i]purin-5-ones: structure-activity relationships and
      characterization of potent and selective inverse agonists at Human A3 adenosine
      receptors.
AB  - Structure-activity relationships of 2-phenyl-imidazo[2,1-i]purin-5-ones as
      ligands for human A(3) adenosine receptors (ARs) were investigated. An ethyl
      group in the 8-position of the imidazoline ring of 4-methyl-2-phenyl
      imidazopurinone leading to chiral compounds was found to increase affinity for
      human A(3) ARs by several thousand-fold. Propyl substitution instead of methyl at
      N4 decreased A(3) affinity but increased A(1) affinity leading to potent A(1)
      selective AR antagonists. The most potent A(1) antagonist of the present series
      was (S)-8-ethyl-2-phenyl-4-propyl-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one
      (S-3) exhibiting a K(i) value of 7.4 nM at rat A(1) ARs and greater than 100-fold
      selectivity versus rat A(2A) and human A(3) ARs. At human A(1) ARs 2
      phenylimidazo[2,1-i]purin-5-ones were generally less potent and therefore less
      A(1)-selective (S-3: K(i)=98 nM). 2-, 3-, or 4-Mono-chlorination of the 2-phenyl
      ring reduced A(3) affinity but led to an increase in affinity for A(1) ARs,
      whereas di- (3,4-dichloro) or polychlorination (2,3,5-trichloro) increased A(3)
      affinity. The most potent and selective A(3) antagonist of the present series was
      the trichlorophenyl derivative (R)-8-ethyl-4-methyl-2-(2,3,5-trichlorophenyl)
      4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (R-8) exhibiting a subnanomolar
      K(i) value at human A(3) ARs and greater than 800-fold selectivity versus the
      other AR subtypes. Methylation of 4-alkyl-2-phenyl-substituted imidazo[2,1
      i]purin-5-ones led exclusively to the N9-methyl derivatives, which exhibited
      largely reduced AR affinities as compared to the unmethylated compounds. [35S]GTP
      gamma S binding studies of the most potent 2-phenyl-imidazo[2,1-i]purin-5-ones at
      membranes of Chinese hamster ovary cells expressing the human A(3) AR revealed
      that the compounds were inverse agonists at A(3) receptors under standard test
      conditions. Due to their high A(3) affinity, selectivity, and relatively high
      water-solubility, 2-phenyl-imidazo[2,1-i]purin-5-ones may become useful research
      tools.

PMID- 12517431
TI  - Research on L-nucleosides. Synthesis and biological evaluation of a series of L-
      and D-2',3'-dideoxy-3'-[tris(methylthio)methyl]-beta-pentofuranosyl nucleosides.
AB  - Novel nucleoside analogues of both D and L enantiomeric series were prepared by
      coupling reaction between a 2',3'-dideoxy-3'-modified furanose moiety and four
      different nucleobases. Though in all cases anomeric mixtures of nucleosides were
      obtained, the presence of the sterically bulky 3'-tris(methylthio)methyl group
      allowed a good stereoselectivity level. All the compounds of both enantiomeric
      series showed high IC(50) values as HSV-1 TK inhibitors and scarce ability to be
      phosphorylated by HSV-1 TK. In order to overcome possible problems related to the
      first phosphorylation step and to facilitate the penetration of the molecule
      through the cellular membrane, a monophosphate prodrug containing a long
      lipophilic chain was synthesized. No appreciable antiviral activity was exhibited
      by this molecule.

PMID- 12517432
TI  - Design, synthesis and biological activity of YM-60828 derivatives. Part 2: potent
      and orally-bioavailable factor Xa inhibitors based on benzothiadiazine-4-one
      template.
AB  - Compound YM-60828 was previously characterized in our laboratory as a potent,
      selective and orally-bioavailable Factor Xa (FXa) inhibitor. The L-shape
      conformation of this compound in the active site of FXa was recognized as an
      important factor in displaying its FXa inhibitory activity. This led to the
      exploration of conformationally restricted cyclic scaffolds bearing a similar
      active conformation. The current study investigated a novel series of
      benzothiadiazine-4-one based compounds as FXa inhibitors. Structure-activity
      relationship (SAR) investigations revealed some potent FXa inhibitors that were
      selected for further in vitro and ex vivo anticoagulant studies. Among them,
      compound 6j (YM-169920) was proved to be most effective anticoagulant in this
      series. The synthesis and SAR in addition to docking studies of this class of
      inhibitors are described.

PMID- 12517433
TI  - Discovery of quinazolines as a novel structural class of potent inhibitors of NF
      kappa B activation.
AB  - We disclose here a new structural class of low-molecular-weight inhibitors of NF
      kappa B activation that were designed and synthesized by starting from
      quinazoline derivative 6a. Structure-activity relationship (SAR) studies based on
      6a elucidated the structural requirements essential for the inhibitory activity
      toward NF-kappa B transcriptional activation, and led to the identification of
      the 6-amino-4-phenethylaminoquinazoline skeleton as the basic framework. In this
      series of compounds, 11q, containing the 4-phenoxyphenethyl moiety at the C(4)
      position, showed strong inhibitory effects on both NF-kappa B transcriptional
      activation and TNF-alpha production. Furthermore, 11q exhibited an anti
      inflammatory effect on carrageenin-induced paw edema in rats.

PMID- 12517434
TI  - Naringenin 7-O-cetyl ether as inhibitor of HMG-CoA reductase and modulator of
      plasma and hepatic lipids in high cholesterol-fed rats.
AB  - Numerous studies in vitro have shown a close relationship between the chemical
      structure and biologic activity of flavonoids, whereby their basic structure is
      modified to increase or decrease their biologic activity. The effects of
      naringenin (1) and its synthetic derivative, naringenin 7-O-cetyl ether (2), on
      the lipid profile, the cholesterol-regulating enzyme activity and the excretion
      of sterol were compared in rats fed a high-cholesterol (1% wt/wt) diet. Either 1
      or 2 was supplemented with a high-cholesterol diet for 6 weeks at a dose of 0.073
      mmol/100g diet. The supplementation of 1 or 2 significantly lowered the levels
      (mean+/-SE) of the plasma total cholesterol (4.93+/-0.19 and 4.75+/-0.16 mmol/L
      vs 5.87+/-0.36 mmol/L, p<0.05) and hepatic triglyceride (0.12+/-0.01 and 0.11+/
      0.01 mmol/g vs 0.18+/-0.01 mmol/g, p<0.05) and cholesterol (0.23+/-0.01 and
      0.21+/-0.01 mmol/g vs 0.31+/-0.01 mmol/g, p<0.05) compared to those of the
      control. The compound 1 or 2 supplementation appeared to decrease the excretion
      of neutral sterols. The plasma HDL-cholesterol concentration and ratio of HDL to
      total cholesterol were significantly higher in 1 and 2 groups than in control
      group. Although the biological effect of 2 on inhibiting hepatic HMG-CoA
      reductase and ACAT activities was only significant compared to the control group,
      both compounds exhibited a significant hypocholesterolemic effect in rats fed a
      high-cholesterol diet. The results suggest that cholesterol biosynthesis and
      esterification were concomitantly reduced by 2, as indicated by the decreased HMG
      CoA reductase and ACAT activities.

PMID- 12517436
TI  - Synthesis, antimicrobial and antifungal activity of a new class of spiro
      pyrrolidines.
AB  - A new class of spiro pyrrolidines, dispiro[oxindole-cyclohexanone]pyrrolidines,
      dispiro[oxindole-tetrahydronaphthalen-1-one]pyrrolidines, dispiro[oxindole
      arylidene-cyclohexanone]pyrrolidines, dispiro[oxindole-hexahydro
      indazole]pyrrolidines, and spiro[butenolide]pyrrolidines, have been screened for
      their antibacterial and antifungal activity against ten human pathogenic bacteria
      and four dermatophytic fungi. They were found to have antimicrobial and
      antifungal activity compounds against various pathogens except Bacillus subtilis.
      The spiro pyrrolidinines were synthesized by the regioselective 1,3-dipolar
      cycloaddition reaction of azomethine ylides generated either from isatin and
      sarcosine or from aziridine. The azomethine ylide so generated reacted with
      various dipolarophiles such as 2-arylidene-cyclohexanones, 2-arylidene
      tetrahydronapthalen-1-ones, 2,6-bis(arylmethylidene)cyclohexanones and 3
      arylidene-5-phenyl- butenolides.

PMID- 12517435
TI  - Rational design, synthesis and biological evaluation of thiadiazinoacridines: a
      new class of antitumor agents.
AB  - A series of potential DNA-binding antitumor agents, 3-[omega-(alkylamino)alkyl]-6
      nitro-thiadiazino[3,4,5-kl]acridines 12 and 1,3-di[omega-(alkylamino)alkyl]-6
      nitro-thiadiazino[3,4,5-kl]acridines 13, has been prepared by cyclization with
      SOCl(2) of 1-[[omega-(alkylamino)alkyl]amino]-9-imino-4-nitro-9,10
      dihydroacridines 16 or 1-[[omega-(alkylamino)alkyl]amino]-9-[omega
      (alkylamino)alkyl]imino-4-nitro-9,10-dihydroacridines 17, respectively. The non
      covalent DNA-binding properties of 12, 13 have been examined using a fluorometric
      technique. In vitro cytotoxic potencies of these derivatives toward six tumor
      cell lines, including human colon adenocarcinoma (HT29) and human ovarian
      carcinoma (A2780 sensitive, A2780cisR cisplatin-resistant, CH1, CH1cisR cisplatin
      resistant, and SKOV-3) cells, are described and compared to that of reference
      drugs. In vivo antitumor activity of some selected derivatives, endowed with
      relevant cytotoxic activity against murine leukemia P388 are reported. The 3-[2
      (dimethylamino)ethyl]-6-nitro-2,7-dihydro-3H-2 lambda(4)-thiadiazino[3,4,5
      kl]acridin-2-one (12d) has been identified as a new lead in the development of
      anticancer tetracyclic acridine derivatives.

PMID- 12517437
TI  - A quantitative structure-activity relationship study on some matrix
      metalloproteinase and collagenase inhibitors.
AB  - A quantitative structure-activity relationship (QSAR) study is made on some
      hydroxamic acid-based inhibitors of matrix metalloproteinases (MMPs) and a
      bacterial collagenase, namely Clostridium histolyticum collagenase (ChC), that
      also belongs to an MMP family, M-31, using Kier's valence molecular connectivity
      index (1)chi(v) of the substituents and electrotopological state (E-state)
      indices of some atoms. The results indicate that out of the four MMPs (MMP-1, MMP
      2, MMP-8, and MMP-9) studied, MMP-2 and MMP-9 can be structurally quite similar,
      but widely differing from MMP-1 and MMP-8 and ChC. For MMP-2 and MMP-9, the
      inhibition activity of compounds is shown to depend on both (1)chi(v )and E-state
      indices, while for MMP-1 and MMP-8 it is shown to depend only on E-state indices
      and for ChC only on (1)chi(v). However, in all the cases, an aromatic group like
      C(6)F(5) or 3-CF(3)-C(6)H(4) attached to SO(2) moiety in the compounds is
      indicated to be equally beneficial, due to probably the involvement of fluorine
      atom(s) in charge-charge interactions with the Zn(2+) ion of the enzymes or in
      the formation of the hydrogen bonds with some sites of the receptors.

PMID- 12517438
TI  - Synthesis of 21,21-difluoro-3 beta-hydroxy-20-methylpregna-5,20-diene and 5,16,20
      triene as potential inhibitors of steroid C17(20) lyase.
AB  - Novel 21,21-difluorovinyl steroids, designed as difluorinated C20(21) enol mimics
      of pregnenolone, were targeted as potential mechanism-based inhibitors of C17(20)
      lyase, a crucial enzyme in the biosynthesis of testosterone. Addition of
      (difluoromethyl)diphenylphosphine oxide reagent to 17-acetyl steroids was the
      approach chosen for the construction of these compounds. Of particular interest
      were the abnormal Wittig products which formed during attempted preparation of
      the triene 9. The target difluoroolefin 3 was found to be a moderately potent,
      time-dependent inhibitor of the enzyme.

PMID- 12517439
TI  - Synthesis and structure-activity relationships of 5,6,7,8-tetrahydropyrido[3,4
      b]pyrazine-based hydroxamic acids as HB-EGF shedding inhibitors.
AB  - HB-EGF Shedding inhibitors have been expected to become effective medicines for
      skin diseases caused by the proliferation of keratinocytes. In order to discover
      novel HB-EGF shedding inhibitors and clarify their structure-activity
      relationships, 5,6,7,8-tetrahydronaphthylidine-based hydroxamic acid and 5,6,7,8
      tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids have been synthesized.
      Among the synthesized compounds, the ethoxyethoxy derivative 3o and the
      methoxypropoxy derivative 3p exhibited much more potent HB-EGF shedding
      inhibitory activity than CGS 27023A. The structural modification of 5,6,7,8
      tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids enabled us to establish
      the following structure-activity relationships; the existence of the hydroxamic
      acid, the sulfonamide, and the phenyl moieties are crucial for a potent HB-EGF
      shedding inhibitory activity, and the stereochemistry of the alpha carbon of
      hydroxamic acid is also important. In addition, from the comparison of their HB
      EGF shedding inhibitory activities with their MMPs inhibitory activities, we
      found that the S1' pocket of the responsible enzyme for HB-EGF shedding is deep
      unlike that of MMP-1.

PMID- 12517440
TI  - Semisynthesis of DB-67 and other silatecans from camptothecin by thiol-promoted
      addition of silyl radicals.
AB  - Thiol- or acid-promoted additions of silyl radicals to camptothecin are reported.
      At 105 degrees C, mixtures of 7-silyl (favored) and 12-silyl camptothecins are
      formed alongside substantial amounts of recovered camptothecin. At 160 degrees C,
      12-silyl isomers are formed preferentially, but the total mass balance is
      substantially reduced. The silyl radical addition is featured in short semi
      syntheses of DB-67 (7-tert-butyldimethylsilyl-10-hydroxy camptothecin) from both
      camptothecin and 10-hydroxycamptothecin.

PMID- 12517441
TI  - Requirement of nucleobase proximal to CpG dinucleotide for immunostimulatory
      activity of synthetic CpG DNA.
AB  - Synthetic oligodeoxyribonucleotides containing CpG dinucleotides exhibit potent
      immunostimulatory activity in vertebrates. Although the molecular mechanisms of
      recognition and interaction of CpG DNA sequences with receptors are not well
      understood, the current evidence suggests that the receptor shows considerable
      selectivity for CpG DNA sequences with different preferences in mouse (GACGTT)
      and human (GTCGTT) species. In our continued effort to understand the chemical
      and structural characteristics of CpG DNA required for the immunostimulatory
      activity and thereby for the recognition of receptors in the immunostimulatory
      pathway, we examined the requirement of nucleobases in the two adjacent
      nucleotide positions on the 5'- and the 3'-side to the CpG dinucleotide
      (P(1)P(2)CGP(3)P(4)) for the immunostimulatory activity. These studies, in which
      a natural nucleoside is substituted with an abasic nucleoside (X), suggest that a
      nucleobase is absolutely required in C, G, P(3), and P(4) positions for
      immunostimulatory activity. Surprisingly, an abasic nucleoside is permitted at
      either P(1) or P(2) depending on the neighboring base. It was found that 'GXCGTT'
      motif has an intermediate immunostimulatory activity between those of 'GACGTT'
      and 'GTCGTT' in the mouse cells.

PMID- 12517442
TI  - Novel strategies for the solid phase synthesis of substituted indolines and
      indoles.
AB  - Using a polymer-bound selenenyl bromide resin, o-allyl and o-prenyl anilines were
      cycloaded to afford a series of solid-supported indoline and indole scaffolds.
      These scaffolds were then functionalized and cleaved via four distinct methods,
      namely traceless reduction, radical cyclization, radical rearrangement, and
      oxidative elimination, to afford 2-methyl indolines, polycyclic indolines, 2
      methyl indoles, and 2-propenyl indolines, respectively. A number of small
      combinatorial libraries of compounds reminiscent of certain designed ligands of
      biological interest were constructed demonstrating the potential utility of the
      developed methodology to chemical biology studies and the drug discovery process.

PMID- 12517444
TI  - AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3
      methylcytosine adducts by a direct reversal mechanism.
AB  - All organisms have multiple DNA repair pathways to protect against alkylation
      induced mutation and cell death. For nearly two decades, we have known that the
      Escherichia coli alkB gene product protects against cell killing by S(N)2
      alkylating agents, probably through DNA repair. Despite numerous attempts, a
      specific DNA repair activity could not be assigned to AlkB. Now, a breakthrough
      in biology and biochemistry, coupled with the discovery of an in silico protein
      structure, has uncovered a novel direct reversal DNA repair mechanism that is
      catalyzed by AlkB, namely the oxidative demethylation of N1-methyladenine or N3
      methylcytosine DNA lesions. This reaction occurs on both single- and double
      stranded DNA, and requires AlkB-bound non-heme Fe(2+), O(2) and alpha
      ketogluterate to oxidize the offending methyl group. This is followed by the
      release of succinate, CO(2) and formaldehyde, and the restoration of undamaged A
      or C in DNA.

PMID- 12517445
TI  - Cellular genomics: which genes are transcribed, when and where?
AB  - Gene expression involves a cascade of events, from transcription factor
      transactivation and RNA polymerase binding to RNA processing and maturation. mRNA
      profiling has yielded a vast amount of information about the total RNA content in
      different tissues physiological states. However, it has been unclear how the
      variable amounts of mRNA might correlate with transcriptional events. Recent
      advances in single-cell imaging offer a platform for 'cellular genomics', the
      high throughput analysis of transcriptional activity in single cells.

PMID- 12517446
TI  - A conserved domain in prokaryotic bifunctional FAD synthetases can potentially
      catalyze nucleotide transfer.
AB  - Biosynthesis of flavin adenine dinucleotides in most prokaryotes is catalyzed by
      a family of bifunctional flavin adenine dinucleotide (FAD) synthetases. These
      enzymes carry out the dual functions of phosphorylation of flavin mononucleotide
      (FMN) and its subsequent adenylylation to generate FAD. Using various sequence
      analysis methods, a new domain has been identified in the N-terminal region that
      is well conserved in all the bacterial FAD synthetases. We also identify remote
      similarity of this domain to the nucleotidyl transferases and, hence, this domain
      is suggested to be invloved in the adenylylation reaction of FAD synthetases.

PMID- 12517447
TI  - Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and
      Galpha-Ggamma interactions.
AB  - Activation of the Galpha subunit of heterotrimeric GTP-binding proteins by
      transmembrane receptors requires the propagation of structural signals from the
      receptor-binding site to the nucleotide-binding site at the opposite side of the
      protein. In a previous model, it was suggested that the Gbeta-Ggamma dimer is
      tilted away from Galpha by a lever-arm motion of the Galpha N-terminal helix.
      Here, we propose that the motion occurs in the opposite direction, close-packing
      the Galpha-Gbeta interface and creating a novel interface between the helical
      domain of Galpha and the N terminus of Ggamma, which determines the specificity
      of activation.

PMID- 12517448
TI  - Is there a unifying mechanism for protein folding?
AB  - Proteins appear to fold by diverse pathways, but variations of a simple mechanism
      - nucleation-condensation - describe the overall features of folding of most
      domains. In general, secondary structure is inherently unstable and its stability
      is enhanced by tertiary interactions. Consequently, an extensive interplay of
      secondary and tertiary interactions determines the transition-state for folding,
      which is structurally similar to the native state, being formed in a general
      collapse (condensation) around a diffuse nucleus. As the propensity for stable
      secondary structure increases, folding becomes more hierarchical and eventually
      follows a framework mechanism where the transition state is assembled from pre
      formed secondary structural elements.

PMID- 12517449
TI  - Transferring substrates to the 26S proteasome.
AB  - Ubiquitin-dependent protein degradation is not only involved in the recycling of
      amino acids from damaged or misfolded proteins but also represents an essential
      and deftly controlled mechanism for modulating the levels of key regulatory
      proteins. Chains of ubiquitin conjugated to a substrate protein specifically
      target it for degradation by the 26S proteasome, a huge multi-subunit protein
      complex found in all eukaryotic cells. Recent reports have clarified some of the
      molecular mechanisms involved in the transfer of ubiquitinated substrates from
      the ubiquitination machinery to the proteasome. This novel substrate
      transportation step in the ubiquitin-proteasome pathway seems to occur either
      directly or indirectly via certain substrate-recruiting proteins and appears to
      involve chaperones.

PMID- 12517450
TI  - Structure, mechanism and regulation of peroxiredoxins.
AB  - Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes that also
      control cytokine-induced peroxide levels which mediate signal transduction in
      mammalian cells. Prxs can be regulated by changes to phosphorylation, redox and
      possibly oligomerization states. Prxs are divided into three classes: typical 2
      Cys Prxs; atypical 2-Cys Prxs; and 1-Cys Prxs. All Prxs share the same basic
      catalytic mechanism, in which an active-site cysteine (the peroxidatic cysteine)
      is oxidized to a sulfenic acid by the peroxide substrate. The recycling of the
      sulfenic acid back to a thiol is what distinguishes the three enzyme classes.
      Using crystal structures, a detailed catalytic cycle has been derived for typical
      2-Cys Prxs, including a model for the redox-regulated oligomeric state proposed
      to control enzyme activity.

PMID- 12517451
TI  - Linking chromatin function with metabolic networks: Sir2 family of NAD(+)
      dependent deacetylases.
AB  - Chromatin remodeling enzymes rely on coenzymes derived from metabolic pathways,
      suggesting a tight synchronization among apparently diverse cellular processes. A
      unique example of this link is the recently described NAD(+)-dependent protein
      and/or histone deacetylases. The founding member of this family - yeast silent
      information regulator 2 (ySir2) - is involved in gene silencing, chromosomal
      stability and ageing. Sir2-like enzymes catalyze a reaction in which the cleavage
      of NAD(+)and histone and/or protein deacetylation are coupled to the formation of
      O-acetyl-ADP-ribose, a novel metabolite. The dependence of the reaction on both
      NAD(+) and the generation of this potential second messenger offers new clues to
      understanding the function and regulation of nuclear, cytoplasmic and
      mitochondrial Sir2-like enzymes.

PMID- 12517452
TI  - Lectin control of protein folding and sorting in the secretory pathway.
AB  - Glycan moieties are essential for folding, sorting and targeting of glycoproteins
      through the secretory pathway to various cellular compartments. The molecular
      mechanisms that underlie these processes, however, are only now coming to light.
      Recent crystallographic and NMR studies of proteins located in the endoplasmic
      reticulum (ER), Golgi complex and ER-Golgi intermediate compartment have
      illuminated their roles in glycoprotein folding and secretion. Calnexin and
      calreticulin, both ER-resident proteins, have lectin domains that are crucial for
      their function as chaperones. The crystal structure of the carbohydrate
      recognition domain of ER-Golgi intermediate compartment (ERGIC)-53 complements
      the biochemical and functional characterization of the protein, confirming that a
      lectin domain is essential for the role of this protein in sorting and transfer
      of glycoproteins from the ER to the Golgi complex. The lectin domains of calnexin
      and ERGIC-53 are structurally similar, although there is little primary sequence
      similarity. By contrast, sequence similarity between ERGIC-53 and vesicular
      integral membrane protein (VIP36), a Golgi-resident protein, leaves little doubt
      that a similar lectin domain is central to the transport and/or sorting functions
      of VIP36. The theme emerging from these studies is that carbohydrate recognition
      and modification are central to mediation of glycoprotein folding and secretion.

PMID- 12517453
TI  - The world's forgotten children.

PMID- 12517455
TI  - Adverts in medical journals: caveat lector.

PMID- 12517456
TI  - Bone marrow transplantation for the heart: fact or fiction?

PMID- 12517457
TI  - Nestle's own goal.

PMID- 12517458
TI  - Lancet correspondence: old letters, new rules.

PMID- 12517460
TI  - Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial
      infarction: a quantitative review of 23 randomised trials.
AB  - BACKGROUND: Many trials have been done to compare primary percutaneous
      transluminal coronary angioplasty (PTCA) with thrombolytic therapy for acute ST
      segment elevation myocardial infarction (AMI). Our aim was to look at the
      combined results of these trials and to ascertain which reperfusion therapy is
      most effective. METHODS: We did a search of published work and identified 23
      trials, which together randomly assigned 7739 thrombolytic-eligible patients with
      ST-segment elevation AMI to primary PTCA (n=3872) or thrombolytic therapy
      (n=3867). Streptokinase was used in eight trials (n=1837), and fibrin-specific
      agents in 15 (n=5902). Most patients who received thrombolytic therapy (76%,
      n=2939) received a fibrin-specific agent. Stents were used in 12 trials, and
      platelet glycoprotein IIb/IIIa inhibitors were used in eight. We identified short
      term and long-term clinical outcomes of death, non-fatal reinfarction, and
      stroke, and did subgroup analyses to assess the effect of type of thrombolytic
      agent used and the strategy of emergent hospital transfer for primary PTCA. All
      analyses were done with and without inclusion of the SHOCK trial data. FINDINGS:
      Primary PTCA was better than thrombolytic therapy at reducing overall short-term
      death (7% [n=270] vs 9% [360]; p=0.0002), death excluding the SHOCK trial data
      (5% [199] vs 7% [276]; p=0.0003), non-fatal reinfarction (3% [80] vs 7% [222];
      p<0.0001), stroke (1% [30] vs 2% [64]; p=0.0004), and the combined endpoint of
      death, non-fatal reinfarction, and stroke (8% [253] vs 14% [442]; p<0.0001). The
      results seen with primary PTCA remained better than those seen with thrombolytic
      therapy during long-term follow-up, and were independent of both the type of
      thrombolytic agent used, and whether or not the patient was transferred for
      primary PTCA. INTERPRETATION: Primary PTCA is more effective than thrombolytic
      therapy for the treatment of ST-segment elevation AMI.

PMID- 12517461
TI  - Medial longitudinal fascicles.

PMID- 12517462
TI  - Radiofrequency lesioning of dorsal root ganglia for chronic lumbosacral radicular
      pain: a randomised, double-blind, controlled trial.
AB  - BACKGROUND: Results of observational studies have shown pain reduction with
      percutaneous radiofrequency lesioning of dorsal root ganglia for lumbosacral
      radicular pain, but there are few randomised controlled trials. We aimed to
      assess the efficacy of radiofrequency lesioning of dorsal root ganglia for
      lumbosacral radicular pain. METHODS: We screened 1001 patients, who were mostly
      referred by their family doctor, in four hospitals for a double-blind randomised
      trial. 83 patients met inclusion criteria and thus were randomly assigned to
      receive a radiofrequency lesion or control treatment of the involved dorsal root
      ganglion. Control treatment was done in the same way as radiofrequency lesioning,
      but without radiofrequency current. Preoperatively and during 3-month follow-up,
      patients reported visual analogue leg-pain and back-pain scores, physical
      impairment, and use of analgesics in a diary. Primary outcome was success or
      failure of treatment, defined by a multidimensional decision rule, which included
      median outcome variables from the diary. Post-hoc analysis for possible covariate
      interference with outcome variables was done. Primary outcome data were analysed
      on an intention-to-treat basis. FINDINGS: 45 patients were assigned
      radiofrequency lesioning and 38 control treatment. Three patients dropped out
      before 3 months. After 3 months, seven (16%) of 44 patients treated with
      radiofrequency lesioning and nine (25%) of 36 in the control group had successful
      treatment (difference -9.1% [95% CI -33.0 to 12.0], p=0.43). No differences
      between groups in side-effects were seen. INTERPRETATION: Lumbosacral
      radiofrequency lesioning of dorsal root ganglia failed to show advantage over
      control treatment with local anaesthetics. Thus, its use as routine treatment in
      lumbosacral radicular pain should not be advocated.

PMID- 12517463
TI  - Accuracy of pharmaceutical advertisements in medical journals.
AB  - BACKGROUND: Because of the effect of the ever-growing evidence-based medicine
      movement on prescribing behaviour of doctors, the pharmaceutical industry
      incorporates bibliographical references to clinical trials that endorse their
      products in their advertisements. We aimed to assess whether the references about
      efficacy, safety, convenience, or cost of antihypertensive and lipid-lowering
      drugs included in advertisements supported the promotional claims. METHODS: We
      assessed all advertisements for antihypertensive and lipid-lowering drugs
      published in six Spanish medical journals in 1997 that had at least one
      bibliographical reference. Two pairs of investigators independently reviewed the
      advertisements to see whether the studies quoted to endorse the advertising
      messages supported the corresponding claims. FINDINGS: We identified 264
      different advertisements for antihypertensive drugs and 23 different
      advertisements for lipid-lowering drugs. We recorded at least one reference in 31
      advertisements in the antihypertensive group and at least one reference in every
      seven advertisements in the lipid-lowering group, providing a total of 125
      promotional claims with references. We could not retrieve 23 (18%) references
      from monographic works and non-published data on file. 79 (63%) of the 125
      references were from journals with a high impact factor; 84 (82%) of the 102
      references retrieved were from randomised clinical trials. In 45 claims (44.1%;
      95% CI 34.3-54.3) the promotional statement was not supported by the reference,
      most frequently because the slogan recommended the drug in a patient group other
      than that assessed in the study. INTERPRETATION: Doctors should be cautious in
      assessment of advertisements that claim a drug has greater efficacy, safety, or
      convenience, even though these claims are accompanied by bibliographical
      references to randomised clinical trials published in reputable medical journals
      and seem to be evidence-based.

PMID- 12517464
TI  - Efficacy and cost-effectiveness of drug and psychological treatments for common
      mental disorders in general health care in Goa, India: a randomised, controlled
      trial.
AB  - BACKGROUND: Common mental disorders are associated with substantial morbidity and
      disability in developing countries, but there are no data for efficacy of
      treatment. We aimed to assess the efficacy and cost-effectiveness of
      antidepressant and psychological treatment for common mental disorders in general
      health-care settings. METHOD: We did a randomised, placebo-controlled trial
      (double-blind for the antidepressant group) in general outpatient clinics in two
      district hospitals in Goa, India. Consecutive eligible adults who scored more
      than 15 on the Revised Clinical Interview Schedule (n=450) were randomly assigned
      to antidepressant (fluoxetine), placebo, or psychological treatment.
      Antidepressant or placebo was provided for up to 6 months. Up to six sessions of
      psychological treatment were provided by trained therapists. The primary outcome
      was psychiatric morbidity; secondary outcomes were disability and costs. Outcome
      measurements were done at 2, 6, and 12 months. Intention-to-treat analyses were
      done with linear regression. FINDINGS: 80% of patients were reviewed; the number
      of drop-outs was similar in all three groups. Psychiatric outcome was
      significantly better with antidepressant than with placebo at 2 months (p=0.02;
      standardised effect size 0.3), but not over the 2-12 month period (p=0.10);
      antidepressants were significantly more cost effective than placebo in the short
      term and long term (p<0.05). Psychological treatment was not more effective than
      placebo for any outcome during either period. INTERPRETATION: Affordable
      antidepressants such as fluoxetine should be the treatment of choice for common
      mental disorders in general health-care settings in India, since they are
      associated with improved clinical and economic outcomes, especially in the short
      term.

PMID- 12517465
TI  - Human papillomavirus type 18 and rapidly progressing cervical intraepithelial
      neoplasia.
AB  - BACKGROUND: Human papillomavirus type 18 (HPV-18) is the second most frequent of
      the HPV types detected when squamous-cell cancer is diagnosed and the type most
      strongly associated with adenocarcinoma of the cervix. However, in cross
      sectional studies, HPV-18 is rarely detected at the time of diagnosis of high
      grade cervical intraepithelial neoplasia (CIN). We used a longitudinal study
      design to describe the occurrence of cytological abnormality after incident HPV
      18 and HPV-16 infections. METHODS: The analysis was based on 1075 women aged 15
      19 years, who had normal cytology and were negative for HPV at recruitment from a
      single family-planning clinic, and who had further follow-up. The women
      reattended every 6 months, and samples were taken for cytological and virological
      examination. FINDINGS: The relative risk of a cytological diagnosis of borderline
      nuclear abnormality after exposure to HPV-18 was 2.06 (95% CI 1.24-3.43) and that
      after exposure to HPV-16 was 1.99 (1.32-3.01). The relative risks of mild
      dyskaryosis were 3.11 (1.86-5.18) and 4.76 (3.15-7.18), and the relative risks of
      moderate or severe dyskaryosis were 0.80 (0.24-2.65) and 2.85 (1.36-5.97). Time
      to acquisition of cytological abnormality was unrelated to the infecting type
      (p=0.88). INTERPRETATION: Our findings do not support the long-held view that the
      reason why HPV-18 infection is under-represented at the time of diagnosis of high
      grade CIN is because HPV-18-associated disease rapidly progresses through the
      preinvasive stages of neoplasia. We suggest that the cytological changes detected
      after HPV-18 infection might understate the severity of underlying disease. This
      feature could compromise the effectiveness of screening programmes in reducing
      the frequency of HPV-18-associated cancers.

PMID- 12517466
TI  - Cotton wool in pine trees.

PMID- 12517467
TI  - Autologous bone-marrow stem-cell transplantation for myocardial regeneration.
AB  - Implantation of bone-marrow stem cells in the heart might be a new method to
      restore tissue viability after myocardial infarction. We injected up to 1.5x10(6)
      autologous AC133+ bone-marrow cells into the infarct border zone in six patients
      who had had a myocardial infarction and undergone coronary artery bypass
      grafting. 3-9 months after surgery, all patients were alive and well, global left
      ventricular function was enhanced in four patients, and infarct tissue perfusion
      had improved strikingly in five patients. We believe that implantation of AC133+
      stem cells to the heart is safe and might induce angiogenesis, thus improving
      perfusion of the infarcted myocardium. See Commentary page 11

PMID- 12517468
TI  - Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow
      mononuclear cell implantation.
AB  - Results of experimental studies have shown that intramyocardial implantation of
      bone marrow cells induces neovascularisation and improves heart function after
      myocardial infarction. Our aim was to test this notion in people. We implanted
      autologous mononuclear bone marrow cells into the ischaemic myocardium of eight
      patients with severe ischaemic heart disease as guided by electromechanical
      mapping with a percutaneous catheter procedure. After 3 months of follow-up,
      there was improvement in symptoms, myocardial perfusion, and function at the
      ischaemic region on MRI. Future randomised, controlled studies are required to
      validate this initial encouraging result.

PMID- 12517469
TI  - High-resolution magnetic resonance angiography of hands with timed arterial
      compression (tac-MRA).
AB  - Timed arterial compression (tac) of blood flow can be achieved by inflation of a
      blood-pressure cuff. We postulated that this technique might improve contrast
      enhanced magnetic resonance angiography (MRA) of the arteries of the hands. We
      studied eight volunteers and six patients with occlusive arterial disease of the
      hands with standard MRA and tac-MRA. Compared with standard MRA, acquisition time
      was extended with the blood-pressure cuff by a factor of four, leading to
      quadrupled image resolution (512x1024). Furthermore, flow-related artifacts were
      not seen. Tac-MRA permits visualisation of the peripheral arterial system in
      finer detail than that achieved with standard MRA.

PMID- 12517470
TI  - The common cold.
AB  - Despite great advances in medicine, the common cold continues to be a great
      burden on society in terms of human suffering and economic losses. Of the several
      viruses that cause the disease, the role of rhinoviruses is most prominent. About
      a quarter of all colds are still without proven cause, and the recent discovery
      of human metapneumovirus suggests that other viruses could remain undiscovered.
      Research into the inflammatory mechanisms of the common cold has elucidated the
      complexity of the virus-host relation. Increasing evidence is also available for
      the central role of viruses in predisposing to complications. New antivirals for
      the treatment of colds are being developed, but optimum use of these agents would
      require rapid detection of the specific virus causing the infection. Although
      vaccines against many respiratory viruses could also become available, the
      ultimate prevention of the common cold seems to remain a distant aim.

PMID- 12517471
TI  - Mistakes are lessons of the past.

PMID- 12517472
TI  - Sexual function in patients treated for benign prostatic hyperplasia.
AB  - CONTEXT: What is the effect of different treatment options for benign prostatic
      hyperplasia (BPH) on sexual function or dysfunction? With increasing age, sexual
      dysfunction and BPH become more prevalent. Some treatments for BPH can affect
      sexual function. Different surgical treatments have different effects on sexual
      function depending on how much the internal involuntary sphincter is affected.
      The same is true for medical therapies, each class of drug having a unique affect
      on sexual function. STARTING POINT: In the past, many articles suggested a causal
      relation between BPH and sexual dysfunction. But a recent report by H Leliefeld
      and colleagues (BJU International 2002; 89: 208-13) confirms the idea that the
      relation is coincidental. Prospectively, these investigators examined patients at
      baseline and 9 months after various treatments for BPH with questionnaires on
      voiding symptoms, related complications, and sexual function. 84% of patients
      reported no change in sexual function. All treatments showed both improvement and
      deterioration in 3-14% and 0-16% of patients, respectively. As expected, age was
      the most important determinant of sexual function. In addition, the effect of
      severe irritative symptoms or the presence of urological comorbidity, such as
      bladder stones, increased the rate of sexual dysfunction. In this study, most
      patients underwent surgical therapy or watchful waiting while fewer had medical
      therapy. Too few patients had minimally invasive procedures to comment on their
      effect on sexual function. WHRE NEXT? Thus the relation between treatment of BPH
      (or watchful waiting) and sexual dysfunction is usually coincidental, unless
      symptoms become severe or complications (such as bladder stones or urinary
      retention) develop. More prospective studies are needed to assess the effect of
      BPH and its treatment on sexual function. Medical therapy is now more common than
      surgery in developed countries and treatment of BPH is commonly advocated for
      improvement in quality of life. Therefore any effects on sexual function become
      even more important. As minimally invasive surgical operations become more
      common, more data will be required for such interventions. The difficulty will be
      in keeping up with the rapidly evolving techniques of minimally invasive
      therapies.

PMID- 12517473
TI  - The hidden alternative: getting investigational treatments off-study.
AB  - Research studies commonly randomise patients between standard care and some new
      form of treatment. In a substantial number of studies, the new treatment could
      have been obtained by the patient directly from their doctor, without
      participating in a study. Yet it is a common practice, endorsed and encouraged by
      the US government, not to advise potential research participants about their
      ability to get the new treatment outside of the study. This policy is even
      occurring in one of the largest studies ever funded by the US government, the
      22000 patient, 5-year comparison of tamoxifen and raloxifene in the prevention of
      breast cancer. This practice has the effect of encouraging more individuals to
      participate in research studies, but the result is that their consent to
      participate is not fully voluntary. Many ongoing studies may therefore be of
      questionable ethical soundness.

PMID- 12517475
TI  - Health and dictatorship: effects of repression in Turkmenistan.

PMID- 12517474
TI  - Women's health and human rights in HIV prevention research.

PMID- 12517476
TI  - The STARD initiative.

PMID- 12517477
TI  - Trade concerns must not be allowed to set the public health agenda.

PMID- 12517478
TI  - The pharmaceutical industry as an informant.

PMID- 12517480
TI  - The pharmaceutical industry as an informant.

PMID- 12517481
TI  - Pfizer Diflucan Partnership Program.

PMID- 12517482
TI  - Open versus laparoscopy-assisted colectomy.

PMID- 12517483
TI  - Open versus laparoscopy assisted colectomy.

PMID- 12517484
TI  - Open versus laparoscopy assisted colectomy.

PMID- 12517485
TI  - Open versus laparoscopy assisted colectomy.

PMID- 12517486
TI  - Open versus laparoscopy assisted colectomy.

PMID- 12517489
TI  - Oral amoxicillin for childhood pneumonia.

PMID- 12517490
TI  - Primary angioplasty or thrombolysis for acute myocardial infarction?

PMID- 12517491
TI  - Primary angioplasty or thrombolysis for acute myocardial infarction?

PMID- 12517492
TI  - Primary angioplasty or thrombolysis for acute myocardial infarction?

PMID- 12517494
TI  - Prevention of coronary artery disease: the south Asian paradox.

PMID- 12517496
TI  - Guidelines for treatment of upper gastrointestinal cancer.

PMID- 12517495
TI  - Prevention of coronary artery disease: the south Asian paradox.

PMID- 12517497
TI  - Guidelines for treatment of upper gastrointestinal cancer.

PMID- 12517498
TI  - Outcome after childhood Henoch-Schonlen purpura.

PMID- 12517499
TI  - Outcome after childhood Henoch-Schonlein purpura.

PMID- 12517501
TI  - Edrecolomab in the adjuvant treatment of colorectal carcinoma.

PMID- 12517502
TI  - Edrecolomab in the adjuvant treatment of colorectal carcinoma.

PMID- 12517506
TI  - Reversible ocular myasthenia gravis or mitochondrial myopathy from statins?

PMID- 12517504
TI  - Dopamine agonists for Parkinson's disease.

PMID- 12517507
TI  - Obesity and type 2 diabetes in Japanese patients.

PMID- 12517508
TI  - Appropriate body-mass index for Asians.

PMID- 12517509
TI  - The dangers of childhood.

PMID- 12517510
TI  - Quadruple treatments for Helicobacter pylori.

PMID- 12517511
TI  - Severe anaemia in west African children: malaria or malnutrition?

PMID- 12517512
TI  - Tianeptine, plasma serotonin, and pulmonary hypertension.

PMID- 12517513
TI  - Physical activity and prevention of type 2 diabetes.

PMID- 12517514
TI  - Simian virus 40 infection in lymphoproliferative disorders.

PMID- 12517515
TI  - New NHS guidelines for PSA testing in primary care.

PMID- 12517517
TI  - Continued threat of Haemophilus influenzae type B disease in the UK.

PMID- 12517518
TI  - Nail in the coffin.

PMID- 12517519
TI  - When the doctor says no.

PMID- 12517524
TI  - A new focus for a new WHO.

PMID- 12517522
TI  - The meaning of detox.

PMID- 12517525
TI  - Nominees for WHO Director General election announced.

PMID- 12517526
TI  - Brundtland's legacy.

PMID- 12517527
TI  - Is industry influencing IARC to downgrade carcinogens?

PMID- 12517528
TI  - Cancer? In Africa?

PMID- 12517529
TI  - WHO's activities in the Eastern Mediterranean Region.

PMID- 12517530
TI  - WHO emphasis on cost-effective cancer-control strategies.

PMID- 12517531
TI  - WHO targets a range of anticancer initiatives in Pacific nations.

PMID- 12517532
TI  - Cancer in the Americas.

PMID- 12517534
TI  - Assessing HRQOL: a neglected issue for high-grade glioma.

PMID- 12517535
TI  - Childhood nasopharyngeal carcinoma: from biology to treatment.
AB  - Nasopharyngeal carcinoma is a rare disease in children with distinct
      epidemiological, histopathological, and clinical characteristics. Incidence
      varies widely around the world but bimodal incidence graphs show that in some
      populations a disproporionate number of cases occur in late childhood. Children
      with nasopharyngeal carcinoma almost always have the undifferentiated variant of
      the disease, which is associated with advanced locoregional spread and distant
      metastases. Both genetic and environmental factors contribute to the development
      of nasopharyngeal carcinoma, as evidenced by its risk factors which include:
      specific HLA subtypes; deletions of chromosomes 3p, 9p, 11q, 13q, and 14q;
      mutations of p53 and RB2/p130; polymorphism of the CYP2E1; and infection with
      Epstein-Barr virus. Traditional treatment consists of high-dose radiotherapy and
      cure rates range between 30% and 60%. The high incidence of failure due to
      systemic disease in children means that chemotherapy is preferable for first-line
      treatment in advanced-stage disease. Currently, cisplatin-based induction or
      adjuvant chemotherapy combinations are used along with high-dose radiotherapy.
      Although combined modality treatment has increased 5-year survival to 70-90%,
      late morbidity is a major concern.

PMID- 12517537
TI  - The safety and tolerability of low-dose irradiation for the management of
      gynaecomastia caused by antiandrogen monotherapy.
AB  - Gynaecomastia--a benign and often painful enlargement of the male breast--is a
      common side-effect of some therapies for prostate cancer, including non-steroidal
      antiandrogen monotherapy. Although gynaecomastia and breast pain are not harmful
      to the overall health of the patient, they can be serious enough to influence
      treatment decisions in the management of prostate cancer. Prophylactic low-dose
      irradiation can be effective in reducing the incidence and severity of both
      gynaecomastia and breast pain. In addition, irradiation may be effective in
      treating breast pain due to the development of gynaecomastia. Low-dose electron
      irradiation confers advantageous tissue dosing, is well tolerated, and has
      manageable side-effects, the most common of which is reversible skin erythema.
      Information on long-term safety after irradiation for gynaecomastia is limited at
      present, but trials are underway. Irradiation is likely to be an effective
      management option with an acceptable low risk of long-term complications for
      gynaecomastia associated with hormone therapy for prostate cancer.

PMID- 12517536
TI  - Emerging pathways in the development of AIDS-related lymphomas.
AB  - The clinicopathological range of AIDS-related non-Hodgkin lymphomas (NHLs)
      includes systemic lymphomas, primary central-nervous-system lymphomas, primary
      effusion lymphoma, and plasmablastic lymphoma of the oral cavity. Most AIDS
      related NHLs belong to one of three categories of high-grade B-cell lymphomas:
      Burkitt's lymphoma, centroblastic lymphoma, and immunoblastic lymphoma. The
      pathological heterogeneity of AIDS-related NHL reflects the heterogeneity of
      their associated molecular lesions. In AIDS-related Burkitt's lymphoma, the
      molecular lesions involve activation of c-MYC, inactivation of p53, and infection
      with Epstein-Barr virus (EBV). AIDS-related immunoblastic lymphomas infected with
      EBV are characterised by frequent expression of latent membrane protein 1-an EBV
      oncoprotein. The biological heterogeneity of AIDS-related NHLs is highlighted by
      their histogenetic differences; AIDS-related NHLs are related to distinct B-cell
      subgroups (eg, germinal-centre or post-germinal-centre B cells). The phenotypic
      pattern of AIDS-related Burkitt's lymphomas and systemic AIDS-related
      centroblastic lymphomas closely reflects that of B cells in germinal centres.
      Conversely, the phenotype of AIDS-related immunoblastic lymphomas and AIDS
      related primary effusion lymphomas reflects post-germinal-centre B cells in all
      cases. Despite their clinicopathological, genetic, and phenotypic heterogeneity,
      most lymphomas in patients with AIDS carry somatic mutations of immunoglobulin
      and BCL-6 genes. However, the somatic hypermutation mechanism functions
      aberrantly in a significant proportion of AIDS-related NHLs, causing the mutation
      of many genes, and possibly favouring chromosomal translocation, which may be a
      powerful contributor to malignant transformation. New molecular and virological
      evidence of such pathways and a greater knowledge of other biological features of
      AIDS-related NHLs may lead to new targets for pathogenetically and biologically
      oriented therapies.

PMID- 12517538
TI  - Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway.
AB  - Tumour resistance and dose-limiting toxic effects restrict treatment with most
      chemotherapeutic drugs. Elucidation of the mechanisms of these effects could
      permit the development of ways to improve the effectiveness of currently used
      agents until better therapeutic agents are developed. Several types of alkylating
      agents are used in the treatment of cancer. The DNA repair protein, O6
      alkylguanine-DNA alkyltransferase (ATase) is an important cellular resistance
      mechanism to one class of alkylating agents. This enzyme removes potentially
      lethal damage from DNA and experiments in vitro and in vivo have shown that its
      inactivation can reverse resistance to such agents. Clinical trials of drugs that
      inactivate ATase are underway and early results indicate that they are active in
      tumour tissues. However, the ATase present in normal tissues, particularly bone
      marrow, is also inactivated, necessitating a reduction in the dose of alkylating
      agent. An important question is whether, in the absence of any tumour-specific
      delivery strategy, such drugs will improve therapeutic effectiveness; initial
      reports are not promising.

PMID- 12517539
TI  - Lung cancer in Europe in 2000: epidemiology, prevention, and early detection.
AB  - Lung cancer is the most common cancer in the world. In men, the highest incidence
      rates are seen in Europe (especially eastern Europe) and North America. In women,
      high incidence rates are found in North America and in Europe, particularly in
      northern and western Europe. It is estimated that there were about 375000 cases
      of lung cancer in Europe in 2000; 303000 in men and 72000 in women. The number of
      resulting deaths was about 347000 (280000 in men and 67000 in women). Tobacco
      smoking is well established as the main cause of lung cancer and about 90% of
      cases are thought to be tobacco related. There is a clear dose-response relation
      between lung-cancer risk and the number of cigarettes smoked per day, degree of
      inhalation, and age at initiation of smoking. Someone who has smoked all their
      life has a lung-cancer risk 20-30 times greater than a non-smoker. However, risk
      of lung cancer decreases with time since smoking cessation. Recently, there has
      been renewed interest in screening because spiral computerised tomography can
      detect small asymptomatic lesions more effectively than conventional radiography.
      Although cure rates for such lesions are very good, there is to date no evidence
      for effectiveness of mass-screening strategies.

PMID- 12517540
TI  - The TNM staging system and breast cancer.

PMID- 12517543
TI  - Paternalistic? Me?

PMID- 12517544
TI  - Blood substitutes: the future is now.

PMID- 12517545
TI  - Effects of morphine analgesia on diagnostic accuracy in Emergency Department
      patients with abdominal pain: a prospective, randomized trial.
AB  - BACKGROUND: Because of concerns about masking important physical findings, there
      is controversy surrounding whether it is safe to provide analgesia to patients
      with undifferentiated abdominal pain. The purpose of this study was to address
      the effects of analgesia on the physical examination and diagnostic accuracy for
      patients with abdominal pain. STUDY DESIGN: The study was a prospective, double
      blind clinical trial in which adult Emergency Department (ED) patients with
      undifferentiated abdominal pain were randomized to receive placebo (control
      group, n = 36) or morphine sulphate (MS group, n = 38). Diagnostic and physical
      examination assessments were recorded before and after a 60-minute period during
      which study medication was titrated. Diagnostic accuracy and physical examination
      changes were compared between groups using univariate statistical analyses.
      RESULTS: There were no differences between control and MS groups with respect to
      changes in physical or diagnostic accuracy. The overall likelihood of change in
      severity of tenderness was similar in MS (37.7%) as compared with control (35.3%)
      patients (risk ratio [RR] 1.07, 95% confidence interval [CI] 0.64-1.78). MS
      patients were no more likely than controls to have a change in pain location
      (34.0% versus 41.2%, RR 0.82, 95% CI 0.50-1.36). Diagnostic accuracy did not
      differ between MS and control groups (64.2% versus 66.7%, RR 0.96, 95% CI 0.73
      1.27). There were no differences between groups with respect to likelihood of any
      change occurring in the diagnostic list (37.7% versus 31.4%, RR 1.20, 95% CI 0.71
      2.05). Correlation with clinical course and final diagnosis revealed no instance
      of masking of physical examination findings. CONCLUSIONS: Results of this study
      support a practice of early provision of analgesia to patients with
      undifferentiated abdominal pain.

PMID- 12517546
TI  - "Components separation technique" for the repair of large abdominal wall hernias.
AB  - BACKGROUND: The "components separation technique" is a method for abdominal wall
      reconstruction in patients with large midline hernias that cannot be closed
      primarily. The early and late results of this technique were evaluated in 43
      patients. METHODS: Records of 43 patients, 11 women and 32 men, with a mean age
      of 49.7 (range 22 to 78), were reviewed for body length and weight, size and
      cause of the hernia, intra- and postoperative mortality and morbidity, with
      special attention given to wound and pulmonary complications. Patients were
      invited to attend the outpatient clinic afterward for at least 12 months for
      physical examination of the abdominal wall. RESULTS: The defect resulted after
      elective surgery in 19 patients and after acute surgery in 24 patients. In 11
      patients, the defect was a result of open treatment of generalized peritonitis,
      and 13 patients had a recurrent incisional hernia. One patient died on the sixth
      postoperative day from mesenteric thrombosis. The postoperative course was
      complicated in 17 patients: fascial dehiscence in one, hematoma in five, seroma
      in two, wound infection in six, skin necrosis in one, and respiratory
      insufficiency in two. Thirty-eight patients were seen for followup. After a mean
      followup of 15.6 months (range 12 to 30 months), a recurrent hernia was found in
      12 of the 38 patients (32%). The remaining four patients had no recurrent hernia
      after 1, 1, 3, and 4 months, respectively. CONCLUSIONS: The "components
      separation technique" is useful for the reconstruction of large abdominal wall
      hernias, especially under contaminated conditions in which the use of prosthetic
      material is contraindicated. Further research is needed to reduce the relatively
      high reherniation rate.

PMID- 12517547
TI  - Concordance with breast cancer pathology reporting practice guidelines.
AB  - BACKGROUND: Accurate pathology reporting is important for treatment of breast
      cancer. The College of American Pathologists (CAP) distributed guidelines for
      reporting cancer specimens in 1998. The aim of this study was to determine
      community-wide concordance with CAP breast cancer reporting guidelines. STUDY
      DESIGN: Pathology reporting of stage I and II breast cancers was examined for
      adherence to CAP guidelines. Pathology reports were reviewed from 100 consecutive
      cases of invasive breast cancers referred to Roswell Park Cancer Institute in
      1998 to 1999 from community hospitals after excisional breast biopsy and 20
      consecutive cases with excisional biopsy at RPCI. Adherence to CAP guidelines for
      clinically relevant items was determined from the original pathology report in
      each case. RESULTS: One hundred one cases met the inclusion criteria. Most
      reports did not include at least one of the guideline required elements. Surgical
      margins were inked in only 77%, and the margins oriented in only 25% of patients.
      Many specimens were not oriented by the surgeon. Grade was reported in most
      cases, but the Bloom Scarf Richardson grade was reported in only 6%. The presence
      or absence of lymphovascular invasion, and of coexisting in situ disease, was
      reported in 57% and 71%, respectively. The extent and type of in situ disease was
      reported in 47% and 49%, respectively. CONCLUSIONS: Breast cancer pathology
      reporting varies widely. Key elements that affect treatment are often omitted.
      These include gross description and size, orientation and involvement of surgical
      margins, and description of histologic features, including Bloom Scarf Richardson
      reporting of grade and the extent of an in situ component. Passive distribution
      of CAP practice guidelines might be insufficient to accomplish community-wide
      quality improvement in breast pathology reporting.

PMID- 12517548
TI  - Prognosis and management of extramammary Paget's disease and the association with
      secondary malignancies.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a rare clinical entity and can
      be associated with other malignancies. We analyzed our experience for prognosis
      and impact of therapy on outcomes. STUDY DESIGN: We conducted a retrospective
      review of all patients (n = 33) with EMPD treated at a tertiary care center from
      1971 to 1998. Pathologic features of EMPD, concurrent secondary malignancies, and
      the effect of operations on recurrence were analyzed. Overall survival was
      compared with that of the general population. RESULTS: Male-to-female ratio was
      4:29, and median age was 70 years. Median followup was 68 months, and no patient
      died from EMPD. The lesion was predominantly found on the vulva (76%). Patch
      like, nonconfluent growth was present in 45% of patients, and no patient had
      pathologic lymph nodes. The most common signs and symptoms were irritation or
      pruritus (73%) and rash (61%). The presence of patches, invasive tumor growth, or
      a second malignancy were significantly associated with a higher recurrence rate.
      The type of operation, either local excision or hemivulvectomy, was not related
      to the time to recurrence. Complete gross resection was achieved in 94% of cases.
      Fifty-six percent of patients had microscopically positive margin and this
      correlated with a significantly higher recurrence rate (p = 0.002). The tumor
      recurred clinically in 14 of 33 patients (42%) after a median of 152 months
      (range 5 to 209 months). In those patients, between one and six reexcisions were
      performed. In 14 of 33 patients with EMPD (42%), 16 concurrent secondary
      malignancies were found. Overall survival rates for EMPD patients were similar to
      those of the general population. CONCLUSIONS: EMPD is an infrequently diagnosed
      disease that is preferably managed with complete local excision and reexcisions
      if needed. A thorough search for frequently occurring secondary malignancies
      might be beneficial to provide the best outcomes for these patients.

PMID- 12517549
TI  - Five-year comprehensive outcomes evaluation in 181 patients after laparoscopic
      Nissen fundoplication.
AB  - BACKGROUND: We conducted an objective followup of 181 patients after laparoscopic
      Nissen fundoplication during a 5-year period after surgery. STUDY DESIGN:
      Patients underwent 24-hour pH recording, esophageal manometry, and symptom score
      assessment for six gastroesophageal reflux disease symptoms preoperatively and at
      6 months, 2 years, and 5 years after surgery. RESULTS: Laparoscopic
      fundoplication was associated with a significant (p < 0.0001) increase in lower
      esophageal sphincter pressure and a significant (p < 0.0001) drop in duration of
      acid reflux in 24 hours, and symptom score, 6, 24, and 60 months after surgery
      when compared with preoperative values. Twenty-one patients (12%) have
      experienced recurrence of reflux-type symptoms, but only six have required repeat
      surgery. Lower esophageal sphincter tone dropped between 6 months and 5 years
      after surgery, but was still an effective antireflux barrier. Patient
      satisfaction with surgery dropped over the 5-year followup but remained high, at
      86%, after 5 years. CONCLUSIONS: Laparoscopic Nissen fundoplication remains an
      effective antireflux procedure at 5 years.

PMID- 12517552
TI  - Impact of antireflux operation on columnar-lined esophagus.
AB  - BACKGROUND: The effect of antireflux operation on the natural history of columnar
      lined esophagus (CLE) is not fully understood. The aim of this study was to
      assess a single center's experience and review the literature on the impact of
      antireflux operation on CLE without high-grade dysplasia. STUDY DESIGN: The
      medical records of 26 patients with CLE but without high-grade dysplasia who
      underwent antireflux operation in our unit were retrospectively analyzed at
      longterm followup with detailed endoscopic investigation. Thirteen patients
      presented with intestinal metaplasia (6 had short segments, and 1 had
      preoperative laser ablation) and 13 without intestinal metaplasia. For the group
      of 13 patients presenting with intestinal metaplasia, the mean endoscopic
      followup was 74.7 months (median 46 months). Three of six with short-segment
      lesion and two of seven with circumferential involvement had complete regression
      of intestinal metaplasia (one after laser therapy). None had progression to
      dysplasia or carcinoma. RESULTS: For the group of 13 patients without intestinal
      metaplasia, mean endoscopic followup was 43.9 months (median 28 months). One had
      complete regression of CLE, and none developed intestinal metaplasia during
      surveillance. CONCLUSIONS: Our study suggests that antireflux operation can alter
      the natural history of CLE, allowing disease stabilization in a substantial
      proportion of patients. After antireflux operation, total regression of CLE is
      possible, but in an unpredictable manner.

PMID- 12517554
TI  - Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection for
      early gastric carcinoma: a review of 43 cases.
AB  - BACKGROUND: Recently, laparoscopy and laparoscopy-assisted surgery have been used
      increasingly as less-invasive alternatives to conventional open surgery. But the
      use of this approach in gastric carcinoma has received little attention, possibly
      from the low incidence of early-stage disease in the West and the relative
      complexity of the surgical procedure. STUDY DESIGN: A prospective feasibility
      study of laparoscopy-assisted distal gastrectomy was performed in patients with
      histologically confirmed gastric carcinoma located in the lower or middle third
      of the stomach. Patients whose preoperative evaluations, including endoscopic
      ultrasonography and computerized tomography, led to a diagnosis of T1 N0 stage
      disease, and who had no advanced disease discovered during laparoscopy, were
      eligible. Intraoperative blood loss, time of operation, mortality, and morbidity
      were assessed, along with the number of lymph nodes retrieved and shortterm
      survival. RESULTS: Between 1998 and 1999, 43 patients were enrolled. Laparoscopy
      assisted distal gastrectomy was converted to an open procedure in one patient.
      There were no operative or in-hospital deaths, but the incidence of anastomotic
      leakage was 14% (6 of 43). The mean blood loss was 239 mL, the time of operation
      was 225 minutes, and lymph node retrieval was 20.2 nodes. These results are
      comparable with a series of conventional open operations. One patient died of
      recurrent disease, and all other patients remain disease-free to date. Port-site
      recurrence was not observed. CONCLUSIONS: Although laparoscopy-assisted distal
      gastrectomy was equivalent to open surgery in several clinical parameters, the
      relatively high morbidity was a drawback. Its appropriateness to gastric cancer
      surgery must be verified by further studies.

PMID- 12517553
TI  - Sentinel lymph node mapping for gastric cancer using a dual procedure with dye-
      and gamma probe-guided techniques.
AB  - BACKGROUND: Increasing evidence supports the sentinel lymph node (SN) concept for
      melanoma and breast cancers. SN biopsy may replace routine lymph node dissection
      in the treatment of these cancers. But there are little data evaluating this
      concept in patients with gastric cancer. The objective of this study was to test
      the feasibility of SN mapping in gastric cancers by using the dual-mapping
      procedure with dye and radioactive colloid. STUDY DESIGN: Thirty-one consecutive
      patients preoperatively diagnosed as T1-2 and N0 underwent SN biopsy using the
      dual-mapping procedure. Distributions of SNs identified by the dye-guided
      technique (blue nodes; BNs) were compared with those identified by the gamma
      probe guided technique (hot nodes; HNs). RESULTS: Among the 31 patients, 7 were
      found to have lymph node metastases. All positive nodes were detected by SN
      biopsy using the dual method. So, an accuracy rate of 100% was achieved in
      predicting the status of regional lymph nodes. Both BNs and HNs were identified
      in 28 of 31 patients (90%), but significant discrepancy of distribution was noted
      between BNs and HNs. Among the 28 patients with identified BNs, there was one
      metastasis in a non-BN. So the accuracy rate was 96% for the dye-guided
      technique. In contrast, among the 28 patients with identified HNs, 2 patients had
      metastasis in non-HNs, making the accuracy rate 93% for the gamma probe-guided
      technique. CONCLUSIONS: SN mapping is feasible in gastric cancer, but the dye
      guided and gamma probe-guided techniques are complementary. So we recommend the
      dual-mapping procedure.

PMID- 12517555
TI  - Longterm survival after extended resections in patients with gallbladder cancer.
AB  - BACKGROUND: Surgery is the treatment of choice for gallbladder cancer, but the
      extent of resection and its benefits remain unclear. STUDY DESIGN: Survival
      analysis of 42 patients who underwent extended resections for gallbladder cancer
      was performed. Resections were labeled R0 (curative) or R1 (noncurative) based on
      histopathologic evaluation. Survival curves were constructed using the Kaplan
      Meier method, and survival data were analyzed by univariate and multivariate
      analyses to identify factors associated with longterm (>2 years) survival.
      RESULTS: R0 status was achieved in 18 patients (43%): 100%, 100%, 45%, and 0% in
      stages I, II, III, and IV, respectively. Patients with R0 resections had a
      significantly better survival than those with R1 resections (median 25.8 months
      versus 17.0 months; p = 0.03). R0 status was achieved in only 3 of 20 patients
      (15%) with node positive (N1) disease compared with 14 of 17 patients (82%) with
      node negative (N0) disease. Patients with N0 disease had a significantly better
      survival than those with N1 disease (median not reached versus 17 months; p =
      0.01). None of the patients with N1 disease survived 5 years; 5-year survival for
      N0 patients was 58%. Adjuvant therapy did not have a significant effect on
      survival. CONCLUSIONS: In patients with gallbladder cancer, R0 status could be
      achieved in only 43% of patients undergoing extended resections. R0 status and N0
      disease were associated with better longterm survival.

PMID- 12517556
TI  - Breast cancer pathology reporting practice and guidelines.

PMID- 12517557
TI  - Pathologic practice standards for breast carcinoma: tumor size, reliable data, or
      miscues?

PMID- 12517558
TI  - How many "surgeries" have you done?

PMID- 12517559
TI  - What's new in colon and rectal surgery.

PMID- 12517561
TI  - Guidelines for withholding or termination of resuscitation in prehospital
      traumatic cardiopulmonary arrest: joint position statement of the National
      Association of EMS Physicians and the American College of Surgeons Committee on
      Trauma.

PMID- 12517562
TI  - Medical professionalism in the new millenium.

PMID- 12517563
TI  - Medical professionalism in the new millenium: a physician charter.

PMID- 12517564
TI  - Preoperative imaging of pancreatic cancer: a management-oriented approach.

PMID- 12517565
TI  - The life and work of the German physician Johannes Scultetus (1595-1645).

PMID- 12517566
TI  - Clinical research for surgeons in palliative care: challenges and opportunities.

PMID- 12517567
TI  - Popliteal artery entrapment syndrome.

PMID- 12517568
TI  - Colonic gallstone ileus.

PMID- 12517569
TI  - Subaquatic laparoscopy for staging of intraabdominal malignancy.

PMID- 12517570
TI  - Vaginoplasty using deepithelialized vulvar transposition flaps: the Grunberger
      method.
AB  - BACKGROUND: One of the most important criteria indicative of the longterm success
      of vaginal enlargement is the absence of postoperative contracture. Numerous
      procedures have been developed for reconstruction of an inadequate vagina. Some
      are technically complex techniques (myo- and fasciocutaneous flaps) with few
      postoperative complications of vaginal contracture, and others implement
      autografts with a greater tendency of tissue contraction. STUDY DESIGN: We report
      here a method of vaginoplasty using deepithelialized vulvar transposition flaps
      to enlarge the width of narrow vaginas found mainly in cases of congenital
      adrenogenital syndrome-associated vaginal atresia, but also in cases of acquired
      vaginal atresia (surgery and radiotherapy-induced). We used deepithelialized
      dermis from the labia majora to construct an enlarged vaginal entrance and
      cavity, a technique that is easy to learn and perform. RESULTS: The healing phase
      of this operation is free of tissue rejection, most likely because of the close
      embryologic relationship of the cornified, paravaginal squamous epithelium of the
      labia majora and the noncornified squamous epithelial lining of the lower third
      of the vagina. The epithelium of the graft loses its cornified layer and becomes
      nonhair-bearing; its cytology and histology mimic normal vaginal epithelium.
      Postoperative function and sexual contentment were reported to be satisfying.
      CONCLUSIONS: The followups of 17 patients who underwent this operation in the
      last 16 years show optimal cosmetic and functional results.

PMID- 12517571
TI  - Adjustable suture-tension closure of the open abdomen.

PMID- 12517572
TI  - Medicine: a science and an art?

PMID- 12517573
TI  - An improved, inexpensive, quick, and easily learned technique for closure of all
      large abdominal trocar wounds after laparoscopic procedures.

PMID- 12517574
TI  - JACS CME-1 featured articles, volume 196, January 2003.

PMID- 12517575
TI  - Allergic. Introduction.

PMID- 12517576
TI  - Role of histamine in the pathophysiology of asthma: immunomodulatory and anti
      inflammatory activities of H1-receptor antagonists.
AB  - Cumulative clinical and laboratory evidence on histamine and its actions suggests
      that it has a pathophysiologic role in asthma. These findings have renewed
      interest in the potential therapeutic role of H1 antihistamines in this disease.
      A murine model of allergen-induced airway inflammation and methacholine-induced
      airway hyperresponsiveness has been used to clarify mechanisms of airway
      function, to identify potential therapeutic targets, and to investigate the
      effects of the H1-receptor antagonist fexofenadine. Findings suggest that there
      may be a role for second-generation antihistamines in treating asthma, with
      patient selection as well as dosing both important therapeutic considerations.
      Because high-dose therapy may be required to achieve a clinical response, agents
      with the widest therapeutic window and the lowest potential for sedation would
      offer the greatest therapeutic potential.

PMID- 12517577
TI  - Treatment of allergic asthma.
AB  - Asthma is a chronic inflammatory disorder of the airways that causes recurrent
      episodes of wheezing, breathlessness, chest tightness, and coughing, particularly
      at night or in the early morning. The airway inflammation also increases
      bronchial hyperresponsiveness to a variety of stimuli. After evaluation that
      includes spirometry, patients with intermittent asthma are treated with a short
      acting bronchodilator on an as-needed basis. Patients with persistent asthma
      should receive inhaled corticosteroids as first-line anti-inflammatory therapy
      and long-acting inhaled beta(2)-agonists as preferred adjunctive therapy.
      Leukotriene modifiers can be used as maintenance therapy in patients with mild
      persistent asthma, or added to the regimen of patients with moderate or severe
      persistent asthma. In patients with asthma and concomitant allergic rhinitis,
      antihistamines may be useful as adjunctive therapy.

PMID- 12517578
TI  - Treatment of allergic rhinitis.
AB  - Allergic rhinitis, a common and often debilitating disease marked by rhinorrhea,
      nasal congestion, nasal itching, and sneezing, is on the increase worldwide.
      Treatment involves allergen avoidance, pharmacotherapy, and, in selected cases,
      immunotherapy. This overview describes the characteristics, pathogenesis, and
      diagnosis of allergic rhinitis. The major contributing allergens of seasonal and
      perennial allergic rhinitis are identified. Pharmacotherapy is described within
      the context of treatment guidelines developed by the major asthma and allergy
      professional organizations. Oral H1 antihistamines are first-line therapy for
      mild-to-moderate allergic rhinitis. The newer, nonsedating agents are recommended
      over first-generation antihistamines. Some of the newer oral antihistamines, such
      as cetirizine, desloratadine, and fexofenadine, have been shown to relieve the
      symptom of nasal congestion. Intranasal steroids are first-line therapy for
      patients with more severe symptoms.

PMID- 12517579
TI  - Pruritic dermatoses: overview of etiology and therapy.
AB  - This review begins with a brief survey of the neurophysiology and neuroanatomy of
      pruritus, and goes on to describe the etiology of the major allergic and
      nonallergic pruritic disorders. The etiology of pruritus often suggests the
      appropriate treatment. For example, urticaria, which is primarily mediated by
      histamine, is amenable to treatment with H1 antihistamines. Second-generation,
      nonsedating antihistamines appear to be more effective than sedating
      antihistamines, perhaps because of better compliance. Other systemic
      pharmacologic options may be useful in nonhistamine-mediated disorders, for
      example, immunomodulators for inflammation-induced pruritus or opiate antagonists
      for atopic dermatitis. Nonpharmacologic measures, such as proper skin care, and
      physical modalities, such as phototherapy or acupuncture, may also be helpful.

PMID- 12517580
TI  - Role of antihistamines in ocular allergy.
AB  - Although H(1) antihistamines are commonly used to treat allergic disorders and
      have demonstrated efficacy in allergic rhinoconjunctivitis, data on the effects
      of these agents specifically on ocular symptoms are limited. Oral H(1)
      antihistamines inhibit some symptoms of pruritus and erythema in laboratory
      models and have been shown to be superior to placebo for relief of symptoms in
      clinical trials. Eye drops typically provide faster relief of ocular symptoms
      than oral agents, and combination therapy with a topical agent and an oral agent
      has been found to be superior to the oral agent alone. In general, oral H(1)
      antihistamines have been considered superior to intranasal corticosteroids for
      relief of ocular symptoms, but some studies have shown equal efficacy for these
      agents, or even superior efficacy for intranasal corticosteroids.

PMID- 12517581
TI  - Comparative pharmacology of H1 antihistamines: clinical relevance.
AB  - H1 antihistamines have similar efficacy in the treatment of allergic disorders;
      however, they differ in terms of their chemical structure, clinical pharmacology,
      and safety. This review focuses on the clinical pharmacology (pharmacokinetics
      and pharmacodynamics) of the newer oral H1 antihistamines (acrivastine,
      cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine,
      and mizolastine). Understanding the pharmacokinetics and pharmacodynamics of
      these H1 antihistamines provides an objective basis for selection of appropriate
      dosages and dose intervals. Pharmacokinetic and pharmacodynamic studies provide a
      rationale for the modified dosage regimens that may be required in special
      populations, such as the very young, the elderly, those with hepatic or renal
      dysfunction, or those taking other medications concurrently. Many H1
      antihistamines are currently available for use. Clinical pharmacology studies
      help physicians to select the best H1 antihistamines for their patients.

PMID- 12517582
TI  - Complementary and alternative medicine herbal therapies for atopic disorders.
AB  - More than 42% of patients with atopic disorders use some type of complementary or
      alternative medicine, underscoring the importance of determining the scientific
      validity of such treatments. This review summarizes herbal therapies from China,
      Japan, Korea, and India, and provides an introduction to some Western
      preparations. Although well-controlled scientific studies of many of the Asian
      herbal therapies have been carried out, and some basic studies have been
      performed for various herbal components (active ingredients), additional research
      is needed to assess the composite effects of many of these remedies.

PMID- 12517586
TI  - Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, in
      maternal and fetal circulation.
AB  - Pronounced dilation of the maternal vasculature occurs during normal pregnancy.
      Likewise, low resistance characterizes the fetoplacental circulation. Nitric
      oxide released by endothelial cells is a potent vasodilator known to be a key
      modulator of both maternal and fetal vascular tone. However, the mechanisms
      underlying the maternal circulatory adaptations and the low resistance of the
      fetal circulation remain unknown. The aim of the present study was to compare
      levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric
      oxide synthase, in the maternal and fetal circulations. High performance liquid
      chromatography was used to measure asymmetric ADMA in the maternal and umbilical
      venous plasma. Plasma ADMA levels during the first trimester were 0.29 +/- 0.05,
      the third trimester before term 0.29 +/- 0.05, and at term 0.32 +/- 0.05 nmol/mL,
      which were significantly (P <.05) lower than the levels measured in nonpregnant
      women (0.41 +/- 0.06 nmol/mL). By contrast, ADMA levels in umbilical venous
      plasma averaged 1.02 +/- 0.18 nmol/mL, significantly (P <.005) higher than
      maternal levels. Unlike ADMA, levels of plasma L-arginine, the nitric oxide
      precursor, did not significantly differ among nonpregnant and pregnant women and
      the fetus.During pregnancy, maternal hemodynamics are modulated, at least in
      part, by a reduction in ADMA. Conversely, the low resistance to umbilical blood
      flow is maintained despite substantially higher fetal ADMA levels. Thus, the
      predominant mechanisms regulating the maternal and fetal circulation apparently
      differ.

PMID- 12517587
TI  - Antioxidant superoxide dismutase attenuates increased endothelial permeability
      induced by platelet-activating factor.
AB  - To study the protective effects of the antioxidant superoxide dismutase (SOD)
      against platelet-activating factor (PAF)-induced endothelial permeability.
      Endothelial cells (ECs) were isolated from human umbilical veins from normal
      pregnancies. The first passage (P1) ECs were grown in polycarbonate transwell
      filters. Confluent ECs were incubated with PAF at concentrations of 2, 5, and 10
      microgram/mL for 2 hours or pretreated with superoxide dismutase. Endothelial
      monolayer permeability was then measured by EC electrical resistance or by the
      leakage of horseradish peroxide (HRP) passing through filters. Endothelial
      junctional protein distribution and expression of VE-cadherin and occludin were
      determined by fluorescent staining of endothelial monolayer and by Western blot
      analysis. mRNA expressions for VE-cadherin and occludin were determined by
      reverse transcriptase-polymerase chain reaction. Data are expressed as Omega.
      cm(2) for electrical resistance and DeltaOD 470 nm for HRP assay and presented as
      mean +/- standard error of the mean. Analysis of variance was used for
      statistical analysis. A P value less than.05 was considered statistically
      significant. Endothelial cell electrical resistance was decreased and HRP leakage
      was increased in ECs treated with PAF. Intercellular gaps were formed at cell
      contact regions in ECs treated with PAF, as evaluated by staining of junctional
      protein VE-cadherin and occludin. The functional changes of the EC barrier and
      the formation of intercellular gaps induced by PAF were concentration dependent,
      which could be partially attenuated by pretreatment of ECs with SOD. Total
      cellular junctional protein expression and mRNA expression of VE-cadherin and
      occludin were not affected by PAF. Increased EC monolayer permeability induced by
      platelet-activating factor is associated with disorganization of EC junctional
      protein distribution of VE-cadherin and occludin. Superoxide dismutase partially
      attenuated the PAF-induced increased endothelial monolayer permeability, which
      suggests that oxidative stress might be involved in the process of PAF-induced
      disturbances of endothelial barrier function.

PMID- 12517588
TI  - Uterine leiomyomas express myometrial contractile-associated proteins involved in
      pregnancy-related hormone signaling.
AB  - We used an animal model to study uterine leiomyoma in the context of pregnancy
      associated changes in gene expression and to determine how they might modulate
      tumor growth. Spontaneous tumors and normal myometrium were collected from Eker
      rats and compared with myometrial samples from pregnant animals. A leiomyoma
      derived cell line was also used to assess pregnancy-related changes in gene
      expression and to determine the impact of signaling by the oxytocin receptor.
      Eker rat leiomyomas expressed several pregnancy-related genes, including connexin
      43, oxytocin receptor (OTR), and cyclooxygenase (COX)-1; however, the tumors did
      not express COX-2, which is expressed in the parturient myometrium. The leiomyoma
      derived cell lines also expressed OTR, which responds to estrogen, binds to
      oxytocin, and exhibits a calcium flux when stimulated with oxytocin. The OTR
      signaling mediated by oxytocin inhibited estrogen-stimulated growth of leiomyoma
      cells. Leiomyoma cells expressed many genes of the parturient myometrium,
      including OTRs, but were deficient in COX-2 expression. Signaling via the OTR
      appears to inhibit estrogen-induced cell proliferation, suggesting that signaling
      by this receptor might help mediate the protective effect of pregnancy on this
      disease.

PMID- 12517589
TI  - Gonadotropin releasing hormone analogue therapy alters signal transduction
      pathways involving mitogen-activated protein and focal adhesion kinases in
      leiomyoma.
AB  - Because gonadotropin releasing hormone analogue (GnRHa) therapy often causes
      leiomyoma regression, in part through alteration of growth factor and receptor
      expression, we determined whether GnRHa therapy alters the expression of
      extracellular signal-regulated kinase (ERK) and focal adhesion kinase (FAK),
      which are linked to intracellular signaling pathways activated by ovarian
      steroids, growth factors, and adhesion molecules. Leiomyoma and matched
      unaffected myometrium were collected from women who received GnRHa therapy (n =
      5) and untreated women (n = 10). We determined the expression of ERK1, ERK2, FAK,
      phosphorylated ERK (pERK1/2), and pFAK using Western blotting and
      immunohistochemical analysis. Leiomyoma and myometrium expressed ERK1 (44 kD),
      ERK2 (42 kD), and FAK (125 kD) at variable levels with increased ERK2, pERK, and
      FAK expression in leiomyoma. We found that GnRHa therapy resulted in a noticeable
      decrease in ERK2 and FAK, with significant reduction in pERK1/2 and low or
      undetectable levels of pFAK in both leiomyoma and myometrium compared with the
      untreated group (P <.05). Immunohistochemically ERK1, ERK2, FAK, pERK1/2, and
      pFAK were localized in smooth muscle cells and connective tissue fibroblasts in
      GnRHa-treated and untreated leiomyoma and myometrium, with considerable reduction
      in their intensity as indicated by HScore in GnRHa-treated tissues. The data
      provide further evidence that leiomyoma regression induced by GnRHa is mediated
      in part through a mechanism involving suppression of signal transduction pathways
      involving growth factors or ovarian steroid and adhesion molecules.

PMID- 12517590
TI  - Hormonal characteristics in the early luteal phase of conceptive and
      nonconceptive menstrual cycles.
AB  - To determine whether serum hormone profiles are different in nonconceptive and
      conceptive menstrual cycles after ovulation and before implantation. Daily blood
      samples obtained during the luteal phase of nonconceptive cycles (n = 31) and
      conceptive cycles (n = 19) were analyzed (intersubject comparison). Samples
      obtained in sequential nonconceptive and conceptive cycles from five subjects
      (intrasubject comparisons) were analyzed to confirm results obtained with
      intersubject analysis. Serum luteinizing hormone (LH), follicle-stimulating
      hormone (FSH), estradiol (E(2)), progesterone, and relaxin were measured by
      immunoassay. A cell-based bioassay was used to determine whether the measurement
      of serum immunoreactive LH is a result of cross-reaction with human chorionic
      gonadotropin (hCG). Intersubject analysis showed that mean serum LH levels were
      significantly higher in conceptive cycles on day 4 and day 5 after the FSH peak
      in urine, and this was confirmed by intrasubject analysis. The addition of
      antibodies that precipitate hCG did not affect the activity of LH receptor ligand
      molecules in serum samples collected during the early luteal phase of conceptive
      cycles, as measured by bioassay. In contrast, this LH receptor binding activity
      was completely removed when precipitating antibodies for LH were added. The mean
      levels of serum E(2) were higher in conceptive cycles after day 4 following the
      FSH peak in urine. The mean values of serum FSH, progesterone, and relaxin were
      not significantly different in nonconceptive and conceptive cycles during the
      same time interval. The differences in luteal phase hormones may reflect
      alterations in signaling in the hypothalamic-pituitary-ovarian axis that begin
      during the preovulatory period of nonconceptive cycles.

PMID- 12517591
TI  - Analysis of an interleukin-6 gene promoter polymorphism in women with
      endometriosis by pyrosequencing.
AB  - Interleukin (IL)-6 has been implicated in the etiology of endometriosis. A single
      nucleotide polymorphism (SNP) at position -174 in the IL-6 gene promoter appears
      to influence IL-6 transcription rates in vitro and basal IL-6 levels in vivo. We
      determined the genotype and the allele frequencies of the -174 IL-6 promoter
      polymorphism and the corresponding IL-6 serum levels in women with endometriosis.
      The pyrosequencing technique was used to assess the IL-6 genotypes in 94 women
      with histologically confirmed endometriosis (study group). A series of 70 healthy
      women without history of uterine disease served as clinical controls (control
      group).Allele frequencies for the G allele among women with and without
      endometriosis were 59.6% and 55.0%, respectively (P =.430; odds ratio [OR] 0.83,
      95% confidence interval [CI] 0.53, 1.29). Homozygotes for the protective allele C
      were present in 17.0% of women with endometriosis and in 18.6% of controls were
      homozygous for the protective allele C (P =.797; OR 0.90, 95% CI 0.40, 2.02).
      When patients with various disease manifestations were compared, we found an
      association between the -174 G allele and chocolate cysts (P =.037). Serum levels
      of IL-6 were significantly higher in women with endometriosis than in controls (P
      <.001), with highest levels in women with chocolate cysts. There was no
      association between serum IL-6 levels and IL-6 genotype. The IL-6 promoter
      polymorphism -174 G/C does not contribute significantly to overall disease
      susceptibility but does predispose the carrier to distinct endometriosis with
      chocolate cysts. A genetically determined high IL-6 response might play a
      pathogenic role in this disease condition.

PMID- 12517592
TI  - Expression of messenger ribonucleic acid encoding steroidogenic enzymes in
      postmenopausal ovaries.
AB  - To investigate expression of steroidogenic enzymes involved in androgen and
      estrogen synthesis in the stroma of postmenopausal ovaries.Ovarian stromal tissue
      samples were obtained at hysterectomy from postmenopausal women who had
      hysterectomy and oophorectomy. Tissues were frozen immediately in liquid nitrogen
      and kept frozen until RNA was extracted. Total RNA was examined by Northern blot
      analysis using (32)P-labeled cDNA probes encoding human P450 side chain cleavage
      (P450(SSC)), P450(17alpha), and cytochrome P450 aromatase (P450(arom)).
      Concentrations of mRNA encoding cytochrome P450(SSC), cytochrome P450 17alpha
      hydroxylase (CYP17), and P450(arom) were determined in the ovarian stroma. We
      detected P450(SSC) mRNA in all postmenopausal ovaries studied. P450(SSC) mRNA was
      increased threefold in the ovarian stroma of postmenopausal women with
      endometrial cancer and endometrial hyperplasia. CYP17 mRNA was detected in the
      ovarian stroma of all women with endometrial cancer. P450(arom) mRNA was not
      detected in the ovaries studied. Postmenopausal ovaries possess enzymes for
      initiation of steroidogenesis. Enzymes essential for androgen synthesis were
      expressed in the ovarian stroma of postmenopausal women with endometrial cancer
      or hyperplasia.

PMID- 12517593
TI  - Effect of 4-hydroxyphenylretinamide on human cervical epithelial and cancer cell
      lines.
AB  - Topical trans-retinoic acid treatment produced a statistically significant
      regression of cervical intraepithelial neoplasia (CIN) 2, but not CIN 3, in
      trials. A promising oral retinoid, 4-hydroxyphenylretinamide (4-HPR) induced
      apoptosis through non-retinoic acid-mediated pathways and is being studied in
      National Cancer Institute phase II trials in several organ sites. We studied the
      effects of 4-HPR on cervical cancer cell lines and on cervical epithelial cell
      lines immortalized by human papillomavirus (HPV). Four immortalized cervical
      epithelial cell lines (in vitro models of precancerous CIN lesions) and nine
      cervical carcinoma cell lines were studied. The growth inhibitory effect of 4-HPR
      was tested in monolayer culture and in semisolid medium, and concentrations
      required for a 50% growth inhibition within 5 days were determined. The agent 4
      HPR inhibited the growth of cervical carcinoma cell lines and HPV-immortalized
      cell lines in a dose- and time-dependent fashion. Doses of 5 and 10 microM were
      more effective than 1 microM. The C33A cell line was most sensitive to 4-HPR, and
      HeLa and HT3 were the least sensitive. Of the HPV-immortalized cell lines, Z132,
      an HPV-16 immortalized cell line, was sensitive; the HPV 18-immortalized cell
      lines (Z173, Z183, and TCL-1) were not, although they were sensitive when grown
      in colonies. The agent 4-HPR is active against several cervical cancer cells
      lines and HPV-immortalized cervical epithelial cell lines. These findings are
      consistent with data from other laboratories studying other organ systems. This
      study helps establish a relevant biologically active dose for clinical trials in
      the cervix, one corresponding to the 5- and 10-microM tissue doses.

PMID- 12517594
TI  - Distinct functional differences of human progesterone receptors A and B on gene
      expression and growth regulation in two endometrial carcinoma cell lines.
AB  - To study the functional differences between the two progesterone receptor
      isoforms (hPRA and hPRB) in human endometrial cancer, two new endometrial
      carcinoma cell lines were created-one expressing hPRA and one expressing hPRB.A
      well-differentiated, hPR-negative Ishikawa cell line was stably transfected with
      either hPRA or hPRB cDNA. Transfected cells were selected, and two cell lines
      expressing approximately equal amounts of receptor were isolated-one expressing
      hPRA (PRA-14) and one expressing hPRB (PRB-59). Cell growth experiments revealed
      a growth-inhibitory response to progestins (MPA and R5020) in the PRB-59 cells
      but not in the PRA-14 cells. Differences in expression of genes targeted by the
      two isoforms were studied using a cDNA expression array technique. A different
      set of genes appeared to be progesterone regulated in the PRA-14 cells than in
      the PRB-59 cells. None of the genes were regulated by both hPRA and hPRB. Insulin
      like growth factor binding protein 3 expression was studied in more detail as an
      example of a gene regulated in PRB-59 cells but not in PRA-14 cells. We
      established a new model to study functional differences between the two hPR
      isoforms in human endometrial carcinoma cells. This model revealed distinctive
      differences in target gene regulation between the two hPR isoforms. Moreover,
      antiproliferative actions of progesterone on human endometrial cancer cells could
      be observed only in the PRB-expressing cell line.

PMID- 12517596
TI  - Rethinking neurosurgical subspecialization.
AB  - In this article, the authors trace the evolution of subspecialty development in
      the relatively young specialty of neurosurgery. The current categorization of
      neurosurgical subspecialties represents an incongruent group of "areas of
      interest" whose origins are historical in their development and whose boundaries
      are indistinct, artificial, and often fail to share a common theme. While
      subspecialty development has undoubtedly improved the quality of care of patients
      with neurosurgical disease in these respective areas, the authors present
      important questions invoked by the artificial boundaries. The current move
      towards formalization of subspecialty training and accreditation, with ultimate
      certification, poses both intended and unintended consequences. The implications
      of these trends in neurosurgery are discussed.

PMID- 12517610
TI  - Comparison of endonasal endoscopic surgery and sublabial microsurgery for
      prolactinomas.
AB  - BACKGROUND: Endonasal endoscopy is a promising minimally invasive surgery for the
      treatment of pituitary adenomas; it is also a good alternative to traditional
      sublabial microsurgery. In this study, we compared endoscopic surgery with
      microsurgery and evaluated both for their safety and effectiveness. We chose
      prolactinomas for study because their hormone and symptomatic changes facilitated
      the comparison. METHODS: During the past five years, 44 randomized prolactinoma
      patients underwent pituitary adenomectomy. Group A (22 patients) underwent
      endonasal endoscopic surgery for prolactinomas. Group B (22 patients) underwent
      sublabial transsphenoidal microsurgery for prolactinomas. RESULTS: In groups A
      and B, patients with prolactinoma exhibited significantly reduced postoperative
      prolactin levels, return of menstrual cycle, and relief of galactorrhea,
      (Wilcoxon signed rank test) (p < 0.001). But there were no statistically
      significant differences in the effectiveness of the procedures used in group A
      and group B. Visual improvement in cases of macroadenoma was satisfactory in both
      groups. Hospital stay in group A ranged from 2-5 days, with a mean of 3.2 days.
      Hospital stay in group B ranged from 4-8 days with a mean of 5.3 days. The
      hospital stay for group A patients was shorter (2.1 days) than for group B
      (Student t test, p < 0.05). The operative time was shorter by 1 hour in Group A
      (mean: 1.7 hours vs. mean: 2.7 hours, p < 0.05). There were fewer complications
      in group A (4.5%) than in group B (27%), p < 0.05. CONCLUSIONS: The endoscopic
      era of pituitary surgery may be coming. Endonasal endoscopic surgery may have the
      same effectiveness as traditional microsurgery. However, endoscopic surgery may
      shorten hospital stay and operative time, and lead to fewer complications. It
      seems to be a good minimally invasive surgical technique for prolactinomas.

PMID- 12517612
TI  - Review: treatment of hydrocephalus in adults.

PMID- 12517615
TI  - The role of postoperative patient posture in the recurrence of chronic subdural
      hematoma: a prospective randomized trial.
AB  - BACKGROUND: Chronic subdural hematoma is known to have a significant recurrence
      rate. In this report, we evaluate the relationship between the recurrence rate of
      chronic subdural hematoma and postoperative patient posture. METHODS: We
      conducted a prospective randomized study of 46 patients with chronic subdural
      hematoma treated surgically at the Osaka City General Hospital from January 1997
      to December 1999. In Group A, the patients were kept in a supine position for 3
      days after the operation. In Group B, the patients assumed a sitting position on
      the day after the operation. RESULTS: The recurrence rates in Group A and Group B
      were not significantly different. CONCLUSIONS: Assuming an upright posture soon
      after operation in cases of chronic subdural hematoma is not thought to be a risk
      factor for recurrence.

PMID- 12517618
TI  - Telemedicine and neurosciences in developing countries.
AB  - It is a universally accepted fact that the number of neurosurgeons in developing
      countries is woefully inadequate. It is also unrealistic to expect this limited
      number to work in professional isolation, in suburban and rural areas, without
      adequate infrastructure. Therefore, this has resulted in concentration of
      neurosurgeons in developing countries, in metropolitan areas, even at the risk of
      being underemployed. The phenomenal advances in communications and information
      technology in India are resulting in a new look at how secondary and tertiary
      health care can be provided to the underprivileged masses. Following a proof of
      concept validation ISRO (Indian Space Research Organization) in conjunction with
      the Apollo Hospitals, is ready to use satellite technology to provide specialist
      care not only to suburban and rural India but to other countries as well, by
      using the large number of highly qualified and trained specialists in urban
      India. The implications of these developments for the delivery of neurosurgical
      care to suburban and rural India is briefly reviewed.

PMID- 12517619
TI  - Diffusion-weighted MR imaging in the preoperative assessment of brain abscesses.
AB  - BACKGROUND: Diffusion-weighted MR imaging (DWI) has recently shown promise in
      differentiating ring-enhancing lesions such as brain abscess and malignant
      neoplasm. The ability of DWI to strongly suggest brain abscess enables a
      neurosurgeon to alter stereotactic planning to optimize diagnosis. We report our
      experience with DWI in 5 patients with lesions on MR imaging and review the
      literature to assess the usefulness of this technique in the preoperative
      evaluation of cerebral abscess. METHODS: The MR images of 5 patients presenting
      with ring-enhancing lesions that ultimately proved to be brain abscesses were
      retrospectively reviewed. In addition to standard MR sequences, trace DWI and
      apparent diffusion coefficient (ADC) calculations were performed on all patients.
      Additionally, 15 recently published articles or references in press concerning
      DWI in cerebral abscesses were reviewed. RESULTS: All lesions were markedly
      hyperintense on DWI and had diminished ADC. Thirty-eight of 39 previously
      reported abscesses were hyperintense on DWI with reduced ADC. Of 165 nonpyogenic
      lesions with DWI findings, 87 were hypointense or isointense, 78 lesions had
      variable hyperintensities, and few manifested the degree of hyperintensity
      observed with abscesses. Most of these included chordomas and epidermoids, which
      are not likely to be confused with abscesses. CONCLUSIONS: Restricted water
      diffusion, as indicated by hyperintensity on DWI and low ADC, in ring-enhancing
      lesions assists in differentiating brain abscess from necrotic tumor. This
      information facilitates stereotactic surgical planning: abscesses should be
      preferentially centrally aspirated, whereas necrotic brain tumors should have
      diagnostic tissue biopsied from cavity walls. Although not definitive for brain
      abscess, restricted water diffusion is an important MR imaging sign and is useful
      in neurosurgical treatment strategies for ring-enhancing lesions.

PMID- 12517621
TI  - Familial ossification of the posterior longitudinal ligament (OPLL) in the
      thoracic spine: case report.
AB  - BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) of the
      spine is most common in the Japanese population and in the cervical spine. We
      present a case of OPLL of the lower thoracic spine in two Caucasian siblings.
      CASE DESCRIPTION: A 58-year-old female presented with lower extremity dysesthesia
      and urinary hesitancy. Family history was significant for a brother who had OPLL
      of the lower thoracic spine removed surgically. Magnetic resonance imaging and
      computed tomography scan of the thoracic spine demonstrated OPLL at T10-11
      causing cord compression and abnormally high T2 signal in the cord. The patient
      underwent posterior decompression with improvement of her symptoms. CONCLUSION: A
      genetic predisposition to develop OPLL has been suggested by previous linkage and
      biochemical studies. While OPLL is an increasingly recognized diagnosis in North
      America, this is the first reported case of familial thoracic OPLL in Caucasian
      siblings.

PMID- 12517623
TI  - A split cord malformation with paresis of the unilateral lower limb: case report.
AB  - BACKGROUND: We report a rare case of split cord malformation. CASE DESCRIPTION: A
      female neonate presented with split cord malformation (SCM) manifesting as right
      lower limb paresis. Myelomeningocele and meningocele were found in the
      lumbosacral region at birth. Magnetic resonance imaging (MRI) demonstrated
      division of the spinal cord into two hemicords below the T5 level. The right
      hemicord formed a hemimyelomeningocele and the left hemicord terminated in the
      low-lying conus. Three-dimensional computed tomography (3D CT) showed extensive
      vertebral body abnormalities. The hemimyelomeningocele was repaired 1 day after
      birth, and septectomy and the repair of the meningocele were performed when the
      patient was 1 year old. The patient has been followed up as an outpatient, and
      has residual right lower limb paresis. CONCLUSION: SCM can be associated with
      multiple spinal abnormalities. MRI and 3D-CT are useful for identifying such
      abnormalities and planning the surgical treatment.

PMID- 12517625
TI  - Alternative management considerations for ethmoidal dural arteriovenous fistulas.
AB  - BACKGROUND: Ethmoidal dural arteriovenous fistulas (EDAFs) are an unusual type of
      intracranial vascular lesion that commonly present with acute hemorrhage. They
      are often best treated surgically; however, recent endovascular advances raise
      questions concerning the best therapeutic approach. METHODS: We present 7 cases
      of EDAFs managed at this institution over a 6-year period, which demonstrate the
      broad spectrum of clinical behavior associated with the lesions. Four patients
      presented with intracranial hemorrhage, 1 patient with rapidly progressive
      dementia, 1 patient with a proptotic, red eye, and 1 with a retro-orbital
      headache. RESULTS: One patient underwent no treatment, 1 underwent embolization
      alone, 2 underwent embolization and resection, and 3 patients underwent resection
      alone. There was complete obliteration of the EDAF in all of the patients who
      underwent surgical resection. Embolization was performed through the external
      carotid circulation and not the ophthalmic artery. There were no treatment
      related neurologic deficits. CONCLUSIONS: Treatment is best managed with a
      multidisciplinary approach, which emphasizes complete resection of the lesions
      with assistance from interventional neuroradiology techniques. However, each
      patient must be evaluated independently as treatment may vary depending on the
      angioarchitecture of the lesion.

PMID- 12517628
TI  - Midbrain hemorrhage presenting with oculomotor nerve palsy: case report.
AB  - BACKGROUND: We report a case of isolated oculomotor nerve palsy caused by a
      midbrain hemorrhage. CASE DESCRIPTION: A 75-year-old man visited our hospital
      complaining of double vision and left eye ptosis without headache. Neuro
      ophthalmic examination showed that his left and right pupils were 3.5 mm and 3 mm
      in diameter, respectively, that left downward eye movement was limited, and that
      convergence of the right eye was limited. Magnetic resonance imaging (MRI)
      demonstrated that there was a hematoma located in the anterior tegmentum of the
      left midbrain. Two weeks after admission and treatment, including conservative
      therapy, his double vision gradually disappeared. CONCLUSION: To date, 73 cases
      have been reported in the literature. Most cases of isolated oculomotor nerve
      palsy have been caused by diabetes mellitus, aneurysm, or infarction. However,
      focal midbrain hemorrhage incidentally produces third nerve palsy. MRI is
      extremely helpful in diagnosing a small hemorrhage of the midbrain in such cases.

PMID- 12517629
TI  - Heterotopic ossification in the orbit.
AB  - BACKGROUND: While calcification of orbital hemangiomas has been reported
      previously, no reports exist of heterotopic ossifications occurring within the
      orbit. CASE DESCRIPTION: A 30-year-old male presented with spontaneous onset of
      painless progressive proptosis of the left eye, with diplopia. The preoperative
      radiologic findings are presented. The lesion was excised completely. The
      pathologic features and probable causes are discussed. CONCLUSIONS: Heterotopic
      ossification of the orbit should be considered in the differential diagnosis of
      an orbital lesion showing radiologic features of calcification or ossification.

PMID- 12517631
TI  - Horsley was the first to use electrical stimulation of the human cerebral cortex
      intraoperatively.
AB  - Fedor Krause has previously been credited with being the first surgeon to use
      electrical stimulation to define epileptic foci in the human cerebral cortex
      before extirpation. We provide evidence indicating that Krause was probably
      preceded by Horsley, and Bidwell and Sherrington in England, and by Keen in the
      United States. Sir Victor Horsley apparently first used electrical stimulation
      diagnostically in 1884 and slightly later (1886) to define epileptic foci.

PMID- 12517632
TI  - "Subspecialization" according to Couldwell and Rovit.

PMID- 12517633
TI  - Practice patterns in the U.S.

PMID- 12517638
TI  - Bacteroides infections in obstetrics and gynecology.

PMID- 12517639
TI  - Neonatal encephalopathy and cerebral palsy: a knowledge survey of Fellows of The
      American College of Obstetricians and Gynecologists.
AB  - OBJECTIVE: To assess practicing obstetricians' knowledge of the etiology and
      pathophysiology of neonatal encephalopathy and its relationship to cerebral
      palsy. METHODS: A questionnaire designed to test both knowledge and practice
      patterns was mailed to 413 members of the Collaborative Ambulatory Research
      Network of The American College of Obstetricians and Gynecologists (ACOG), as
      well as 600 randomly selected non-Network ACOG Fellows. The questionnaire was
      composed of 15 knowledge questions and three clinical scenarios containing seven
      knowledge questions. Six of the questions directly assessed knowledge of cerebral
      palsy. RESULTS: Of those who returned the questionnaire, 351 practiced obstetrics
      and were included in the statistical analyses. For the majority of questions,
      "Don't know" was the most frequent response. The next most frequent response for
      8/13 questions was the correct answer. Performance was strongest as regarded
      actual clinical practice and relatively weak regarding the antecedents of
      neonatal encephalopathy and cerebral palsy. The physicians' actual knowledge
      scores showed a significant correlation with their self-assessments of knowledge
      (r =.41, P <.001). The majority of physicians rated their training on this topic
      in medical school, residency, and through continuing medical education as
      marginal or inadequate. CONCLUSION: The results of this survey identified large
      knowledge gaps in this area, suggesting a need to develop educational projects to
      address these deficits by both professional organizations and individual
      teachers.

PMID- 12517640
TI  - Two-year outcome of infants weighing 600 grams or less at birth and born 1994
      through 1998.
AB  - OBJECTIVE: To assess the neurologic and developmental outcome at 2 years of age
      in preterm infants with birth weights 600 g or lower. METHOD: We conducted a
      retrospective review from January 1994 through December 1998 for placental
      histopathology, maternal factors, neonatal intensive care unit course, growth,
      neurologic/special sense status, and development at 2 years of age corrected for
      prematurity. RESULTS: Of the 104 neonates weighing 600 g or less, 24 survived to
      nursery discharge (23%). Two infants died of chronic lung disease after
      discharge, and 21 of the remaining 22 infants (95%) returned for follow-up.
      Placental pathology was available for 21 (95%); acute inflammation was present in
      67%, and other abnormalities occurred in 76%. Mean birth weight was 537 (430-600)
      g, and mean gestational age was 24 (22-27) weeks. At birth, 55% were below the
      tenth percentile for birth weight. At nursery discharge and 2 years of age, 94%
      were below the tenth percentile for weight, length, and head circumference.
      Nineteen of 21 (90%) infants were abnormal on neurodevelopmental follow-up. Major
      problems were cerebral palsy, blindness, gastrostomies, and ventriculoperitoneal
      shunts. CONCLUSION: Abnormal placental histology was present in all but one
      infant, suggesting fetal injury before birth. Only eight of 20 infants with
      chorioamnionitis were diagnosed clinically, and all infants had a complicated
      course. We found a high incidence of intrauterine growth restriction and an
      almost universal pattern of impaired postnatal growth with extremely poor
      neurodevelopmental outcome at 2 years of age.

PMID- 12517641
TI  - Is maternal obesity a predictor of shoulder dystocia?
AB  - OBJECTIVE: To explore the relationship between maternal obesity and shoulder
      dystocia while controlling for the potential confounding effects of other
      variables associated with obesity. METHODS: We performed a case-control study of
      provincial delivery records audited by the Northern and Central Alberta Perinatal
      Outreach Program. Risk factors evaluated were selected based on previously
      published studies. Cases and controls were drawn from 45,877 live singleton
      cephalic vaginal deliveries weighing more than 2500 g between January 1995 and
      December 1997. There were 413 cases of shoulder dystocia (0.9% incidence).
      Controls (n = 845) were randomly chosen from the remainder of the target
      population to create a 1:2 case/control ratio. Univariate analysis with
      calculation of odds ratios (ORs) was used to determine which of the chosen risk
      factors were significantly related to the incidence of shoulder dystocia.
      Multivariable regression analyses were then used to determine the independently
      associated variables, and the adjusted ORs were obtained for each relevant risk
      factor. RESULTS: Maternal obesity was not significant as an independent risk
      factor for shoulder dystocia after adjusting for confounding variables (adjusted
      OR 0.9; 95% confidence interval [CI] 0.5, 1.6). Fetal macrosomia was the single
      most powerful predictor. The adjusted ORs were 39.5 (95% CI 19.1, 81.4) for birth
      weight greater than 4500 g and 9.0 (95% CI 6.5, 12.6) for birth weight between
      4000 and 4499 g. CONCLUSION: The strongest predictors of shoulder dystocia are
      related to fetal macrosomia. For obese nondiabetic women carrying fetuses whose
      weights are estimated to be within normal limits, there is no increased risk of
      shoulder dystocia.

PMID- 12517642
TI  - Screening interval and risk of invasive squamous cell cervical cancer.
AB  - To compare the risks of developing invasive squamous cell cervical cancer
      associated with screening intervals of 1, 2, and 3 years after a negative
      cervical smear. We conducted a matched case-control study of invasive squamous
      cell cervical cancer patients (n = 482) diagnosed between 1983 and 1995 among
      long-term members of a large health maintenance organization. Controls were
      matched for age, length of membership, and race (n = 934). Screening interval was
      time between the last negative cervical smear and the case diagnosis date. The
      main outcome measure was the relative odds of invasive disease associated with 1
      year, 2-year, and 3-year intervals. The odds ratio for a 2-year versus a 1-year
      interval was 1.72 (95% confidence interval 1.12, 2.64, P =.013) and for a 3-year
      versus a 1-year interval was 2.06 (95% confidence interval 1.21, 3.50, P =.007).
      The odds ratio for a 3-year versus a 2-year interval was 1.20 (95% confidence
      interval 0.65, 2.21, P =.561). Controlling for ever having had an abnormal
      cervical smear or a previous consecutive negative smear did not substantially
      change these results. In this large health plan, the relative risks of invasive
      squamous cell cervical cancer were significantly greater for 2-year and 3-year
      cervical cancer screening intervals compared with a 1-year interval, but not for
      a 3-year interval compared with a 2-year interval. Our findings need to be placed
      in the context of the low absolute risks of developing invasive cervical cancer
      during the first 3 years after a negative cervical smear before making policy
      recommendation.

PMID- 12517643
TI  - Cervical cancer: effect of glandular cell type on prognosis, treatment, and
      survival.
AB  - OBJECTIVE: To investigate survivals from cervical cancer, with special reference
      to effects of glandular histology and its influence on prognostic characteristics
      and management decisions. METHODS: Data on cervical cancers, diagnosed in 1984
      2000, were obtained from the gynecologic oncology registry of hospitals of the
      University of Adelaide. Comparisons were made of disease-specific survival, age
      at diagnosis, diagnostic period, stage, grade, and primary course of treatment.
      RESULTS: The study included 544 squamous cell carcinomas, 43 adenosquamous
      carcinomas, five clear cell cancers, 136 other adenocarcinomas, and 19 cancers of
      "other" histological type. Overall survival was 72.2% at 5 years from diagnosis,
      decreasing to 67.5% at 15 years. Survival was lower for older ages, higher
      grades, and higher International Federation of Gynecology and Obstetrics stages,
      although equivalent for stages IIA and IIB. Unadjusted survivals varied by
      histological type (P =.001), with lower survivals suggested for adenosquamous and
      clear cell lesions and "other" histological types than for squamous cell
      carcinomas and other adenocarcinomas. After adjusting for age, stage, grade, and
      diagnostic period, adenocarcinomas had a higher case fatality than squamous cell
      lesions (relative risk 2.08, 95% confidence limit 1.35, 3.21), whereas the
      elevation in relative risk was lower and not statistically significant for a
      combined adenosquamous and clear cell category at 1.25 (0.69, 2.24). For stage
      II, both adenocarcinomas and the adenosquamous and clear cell group had lower
      survivals than squamous cell cancers. CONCLUSION: Relative to squamous cell
      carcinomas, adenocarcinomas and potentially adenosquamous cancers are becoming
      more common. This has implications for screening, treatment, and prognosis.

PMID- 12517644
TI  - The appearance of levator ani muscle abnormalities in magnetic resonance images
      after vaginal delivery.
AB  - OBJECTIVE: To describe the appearance and occurrence of abnormalities in the
      levator ani muscle seen on magnetic resonance imaging (MRI) in nulliparous women
      and in women after their first vaginal birth. METHODS: Multiplanar proton density
      magnetic resonance images were obtained at 0.5-cm intervals from 80 nulliparous
      and 160 vaginally primiparous women. These had been previously obtained in a
      study of stress incontinence, and half the primiparas had stress incontinence.
      All scans were reviewed independently by at least two examiners blinded to parity
      and continence status. RESULTS: No levator ani defects were identified in
      nulliparous women. Thirty-two primiparous women (20%) had a visible defect in the
      levator ani muscle. Defects were identified in the pubovisceral portion of the
      levator ani in 29 women and in the iliococcygeal portion in three women. Within
      the pubovisceral muscle, both unilateral and bilateral defects were found. The
      extent of abnormality varied from one individual to the next. Of the 32 women
      with defects, 23 (71%) were in the stress incontinent group. CONCLUSION:
      Abnormalities in the levator ani muscle are present on MRI after a vaginal
      delivery but are not found in nulliparas.

PMID- 12517645
TI  - Severity of mastalgia in relation to milk duct dilatation.
AB  - OBJECTIVE: The etiology of mastalgia is poorly understood. Histology cannot
      detect any distinct characteristics. This investigation therefore applied
      ultrasonography to mastalgia patients to investigate morphological structures and
      to obtain further insights into the pathophysiology of mastalgia. The aim of the
      study was to analyze the significance of milk duct dilatation in patients with
      mastalgia. METHODS: A total of 335 premenopausal women participated in a genital
      and breast cancer screening program. Of these, 123 women were asymptomatic and
      212 complained of breast pain (136 had cyclical mastalgia; 76 reported the
      noncyclical type). The width of milk ducts was measured by ultrasonography and
      correlated with the intensity of breast pain. The site of the pain was correlated
      with duct dilatation. Statistical analysis was performed using the t test, the
      chi(2) test, analysis of variance, and Pearson correlation. RESULTS: In
      asymptomatic women, the maximum mean width of the milk ducts was 1.8 +/- 0.84 mm,
      in cyclical mastalgia 2.34 +/- 1.10 mm, and 3.89 +/- 1.26 mm in noncyclical
      mastalgia (P <.001). The intensity of pain showed a significant, positive
      correlation with the width of the milk ducts (r =.5008, P <.001). Noncyclical
      mastalgia patients located the pain at the site where dilated ducts were detected
      ultrasonographically (P <.001). CONCLUSION: The results of this study demonstrate
      that duct ectasia is a major factor in mastalgia. The degree of duct dilatation
      correlates positively with the intensity of breast pain. In the noncyclical type
      of pain, there is a positive correlation between the site of duct dilatation and
      the site of pain.

PMID- 12517646
TI  - Detection of cesarean scars by transvaginal ultrasound.
AB  - OBJECTIVE: To assess the ability of transvaginal ultrasound to detect cesarean
      scars and their defects in the nonpregnant state. METHODS: Asymptomatic, parous
      volunteers underwent transvaginal ultrasound of the cervix, uterus, and adnexa.
      Uterine measurements, the presence or absence of a cesarean scar, and the
      presence of a scar defect, defined as fluid within the scar, were recorded. All
      subjects completed a self-report questionnaire regarding obstetric history.
      Sonographers and investigators were blinded to subject history. RESULTS: A total
      of 70 subjects were enrolled. Of these, 38 women had a prior vaginal delivery and
      32 women a prior cesarean delivery. One woman with a bicornuate uterus and three
      cesarean deliveries was excluded from data analysis. Real-time transvaginal
      ultrasound proved 100% sensitive (exact 95% confidence interval [CI] 88.8, 100)
      and 100% specific (exact 95% CI 90.7, 100). Stored image review had a sensitivity
      of 87% (exact 95% CI 70.2, 96.4) and a specificity of 100% (exact 95% CI 90.7,
      100). Fluid was visualized within the scars of 13 of 31 subjects (42%) with a
      prior cesarean delivery. All 13 were found among the 23 subjects (56%) who had
      labored prior to cesarean delivery. Moreover, women with cesarean scar defects
      had a greater number of cesarean deliveries (P <.04) than women without scar
      defects. CONCLUSIONS: Transvaginal ultrasound is highly accurate in detecting
      cesarean hysterotomy scars. Cesarean scar defect, defined by the presence of
      fluid within the incision site, was more common when labor preceded cesarean
      delivery and with multiple cesarean deliveries.

PMID- 12517647
TI  - Postpartum seizure prophylaxis: using maternal clinical parameters to guide
      therapy.
AB  - OBJECTIVE: To use individual patient clinical parameters to signal cessation of
      postpartum magnesium sulfate seizure prophylaxis for the spectrum of pregnancy
      related hypertensive disorders. METHODS: This was a prospective study using
      clinical symptoms (absence of headache, visual changes, epigastric pain) and
      signs (sustained blood pressure less than 150/100 without need for acute
      antihypertensive therapy, spontaneous diuresis more than 100 mL per hour for no
      less than 2 hours) to signal cessation of intravenous magnesium sulfate
      postpartum in gravidas diagnosed with preeclampsia, eclampsia, and hemolysis,
      elevated liver enzymes, low platelets syndrome. Laboratory assessments (including
      proteinuria) were not used as criteria for drug discontinuation. RESULTS: Five
      hundred three patients were enrolled and classified according to American College
      of Obstetricians and Gynecologists criteria (mild preeclampsia, severe
      preeclampsia, chronic hypertension with superimposed preeclampsia, eclampsia, and
      hemolysis, elevated liver enzymes, low platelets syndrome). Maternal age,
      gestational age, and hours of magnesium therapy before delivery were not
      statistically different among groups. There was no significant difference in the
      duration of postpartum magnesium sulfate therapy among groups with the median
      duration of therapy 4 hours (range 2-77 hours). No eclamptic seizures occurred
      after magnesium discontinuation. Thirty-eight patients (7.6%) required
      reinstitution of magnesium therapy for 24 hours because of exacerbation of blood
      pressure (sustained blood pressure more than 160/110) associated with headache or
      visual changes. CONCLUSION: Clinical criteria, when compared with arbitrary
      protocols, can be used successfully to shorten the duration of postpartum
      magnesium sulfate administration for seizure prophylaxis in patients with
      pregnancy-related hypertensive disorders.

PMID- 12517648
TI  - A randomized trial of oral and vaginal misoprostol to manage delivery in cases of
      fetal death.
AB  - OBJECTIVE: To compare the effectiveness and side effects of oral and vaginal
      misoprostol for the termination of second and third trimester pregnancy with
      intrauterine fetal death. METHODS: Eighty pregnant women at 16-41 weeks'
      gestation with intrauterine fetal death were randomized in two groups to receive
      either 400 micro g of misoprostol orally every 4 hours (n = 40) or 200 micro g of
      misoprostol vaginally every 12 hours (n = 40) until the termination of pregnancy
      was completed. The adverse effects, progress, and outcomes of delivery were
      assessed. RESULTS: The groups were similar in age, weight, height, gestational
      age, parity, and modified Bishop scores before intervention. The mean induction
      to-delivery time in the oral group (13.95 [standard deviation (SD) = 5.63] hours)
      was significantly shorter than the time in the vaginal group (18.87 [SD = 10.38]
      hours, P =.001). The number of deliveries within 24 hours after the initial drug
      administration in the oral group (92.5%) was significantly higher than the number
      in the vaginal group (67.5%, P <.001), and all delivered within 48 hours after
      the initial drug administration. However, the gastrointestinal side effects in
      the oral group was significantly higher than in the vaginal group (P =.005).
      CONCLUSION: Misoprostol (400 micro g given orally every 4 hours) was more
      effective than misoprostol (200 micro g given vaginally every 12 hours) for the
      termination of second and third trimester pregnancy with intrauterine fetal
      death, but with more gastrointestinal side effects.

PMID- 12517649
TI  - Correlates of antibiotic-resistant group B streptococcus isolated from pregnant
      women.
AB  - Despite antibiotic prophylaxis for at-risk mothers during labor and delivery,
      group B streptococcus still causes substantial morbidity and mortality among
      newborns. Resistance to antibiotics recommended for penicillin-allergic pregnant
      women, such as erythromycin and clindamycin, has increased. A better
      understanding of factors associated with group B streptococcus resistance is
      essential to effectively prevent group B streptococcus disease.A total of 117
      sequential group B streptococcus isolates were obtained between August 1999 and
      March 2000 from pregnant women at the University of Michigan Medical Center.
      Serotype and susceptibility to ten antimicrobials using disk diffusion with E
      test for confirmation were determined, and the association between several host
      factors and colonization with a resistant strain was evaluated. Group B
      streptococcus was frequently resistant to erythromycin (29%) and clindamycin
      (21%) but was susceptible to all other antimicrobials tested. A stepwise logistic
      regression model revealed that black ethnicity (P =.02) and carriage of a
      serotype V strain (P =.01) were associated with group B streptococcus resistance.
      Among this population of pregnant women, black ethnicity and serotype V were the
      strongest predictors of colonization with an erythromycin- or clindamycin
      resistant group B streptococcus strain. A better understanding of factors
      associated with antibiotic resistance is needed to minimize group B streptococcus
      disease risks and to maximize effective chemoprophylaxis.

PMID- 12517650
TI  - The effect of intraabdominal irrigation at cesarean delivery on maternal
      morbidity: a randomized trial.
AB  - To determine if intraabdominal irrigation with normal saline at cesarean delivery
      is associated with increased maternal morbidity. One hundred ninety-six women
      undergoing routine cesarean delivery at at least 37 weeks' gestation were
      prospectively randomized to receive 500-1000 mL of normal saline intraabdominal
      irrigation versus no irrigation after closure of the uterine incision, but before
      abdominal wall closure. Data were collected for comparison of demographic
      factors, intrapartum and postpartum complication rates, and maternal and neonatal
      outcomes. The primary outcome measure was the combined incidence of maternal
      morbidity, defined as at least one of the following: postoperative infectious
      morbidity, postpartum hemorrhage, severe anemia, and urinary retention.Ninety
      seven patients were randomized to the irrigation group and 99 to the control
      group. The demographic characteristics of the two groups were similar. Thirteen
      patients (13.1%) in the control group and 14 patients (14.4%) in the irrigation
      group experienced maternal morbidity (P =.84). There were no statistically
      significant differences between the groups in estimated blood loss, operating
      time, incidence of intrapartum complications, hospital stay, return of
      gastrointestinal function, incidence of infectious complications, or neonatal
      outcomes.Routine intraabdominal irrigation at cesarean delivery in a low-risk
      population does not reduce intrapartum or postpartum maternal morbidity.

PMID- 12517651
TI  - Severe preeclampsia and cerebral blood volume response to postural change.
AB  - OBJECTIVE: To compare the cerebral blood volume response, measured by near
      infrared spectroscopy, to a change in maternal posture in pregnant women with and
      without the hypertensive disorders of pregnancy. METHODS: Normotensive (n = 13),
      chronic hypertensive (n = 7), pregnancy-induced hypertensive (n = 9), and
      preeclamptic (n = 15) women were studied cross-sectionally. The change in
      cerebral blood volume in response to a change in maternal posture from the left
      lateral to sitting position was quantified. RESULTS: In the normotensive, chronic
      hypertensive, and pregnancy-induced hypertensive groups there was a fall in
      median (interquartile range) cerebral blood volume of 0.18 (-0.21, -0.15), 0.11 (
      0.26, -0.09), and 0.089 (-0.10, -0.049) mL/100 g, respectively. Conversely, in
      the preeclamptic group there was a rise in median cerebral blood volume of 0.13 (
      0.20, 0.15) mL/100 g. Of these, six of the nine women with a median rise in
      cerebral blood volume of 0.15 mL/100 g (0.13, 0.16) required intravenous
      antihypertensive therapy, volume expansion, and delivery by cesarean within 48
      hours. Conversely, none of the preeclamptic women (n = 6) with a median fall in
      cerebral blood volume of 0.22 mL/100 g (-0.30, -0.18) required these emergency
      measures. CONCLUSION: The cerebral blood volume response, measured noninvasively
      by near-infrared spectroscopy, provides additional evidence of altered cerebral
      hemodynamics in women with preeclampsia.

PMID- 12517652
TI  - Is burning semen syndrome a variant form of seminal plasma hypersensitivity?
AB  - OBJECTIVE: To identify an index population of Gulf War couples with burning semen
      syndrome and to determine whether burning semen syndrome was secondary to seminal
      plasma hypersensitivity. METHODS: Questionnaire surveys, screening laboratory
      testing for underlying medical disorders, including sexually transmitted diseases
      and immunoglobulin G and E immunoassays specific for seminal plasma protein, were
      performed. If subjects met the criteria for seminal plasma hypersensitivity, the
      Gulf War male veteran's seminal plasma proteins were used to desensitize his
      female sexual partner. RESULTS: Eighty-nine percent (188 of 211) of respondents
      had either personally experienced burning after contact with their own semen or
      had a sexual partner who had burning after contact with their semen. Asymptomatic
      female partners (three of five) of Gulf War veterans who exhibited specific
      immunoglobulin E skin and antibody responses to seminal plasma proteins responded
      successfully to rapid desensitization. Treatment results were confirmed by a
      provocative office challenge, consisting of instillation of whole seminal fluid
      into the female's vaginal vault and, if negative, subsequently by natural coitus.
      CONCLUSION: The results of this study indicate that seminal plasma
      hypersensitivity may present as burning semen syndrome in a subpopulation of Gulf
      War couples. Proper screening of Gulf War couples with clinical features of
      burning semen syndrome should include assessment for seminal plasma
      hypersensitivity reactions, as seminal plasma protein desensitization may induce
      remission of burning semen syndrome.

PMID- 12517653
TI  - Prevalence of sexual abuse among women seeking gynecologic care in Germany.
AB  - OBJECTIVE: To estimate the prevalence of sexual abuse among patients seen for
      gynecologic care in Germany. METHODS: A short anonymous questionnaire was
      distributed to 1157 women attending a gynecologic outpatient clinic at a large
      urban teaching hospital. Data collected using the questionnaire included patient
      characteristics, sexual abuse history, and screening practices. Women who
      reported that they had been abused were asked if they had ever discussed the
      issue with their gynecologist. RESULTS: A total of 1075 questionnaires were
      returned, for a response rate of 92.9%. Almost half (n = 479 [44.6%]) of the
      women surveyed reported that they had been the subject of unwanted sexual
      attention. One fifth (n = 216 [20.1%]) had been forced to engage in sexual
      activities: 6.8% in childhood, 10.3% during adolescence, 6.4% as an adult, and
      3.5% across more than one stage. Thirteen women (6%) reported having discussed
      the abuse with their gynecologist. Sixty-six (30.5%) were too afraid to raise the
      issue, and 119 (55.1%) stated it was not relevant to their care. Only one woman
      (0.5%) reported that her gynecologist had asked about sexual abuse. CONCLUSION:
      Despite the high prevalence of sexual abuse among women seeking gynecologic care,
      routine screening does not appear to be part of standardized practice.

PMID- 12517654
TI  - Oil-soluble contrast during hysterosalpingography in women with proven tubal
      patency.
AB  - To determine if there are therapeutic advantages to oil-soluble contrast medium
      compared with water-soluble medium during hysterosalpingography.A randomized,
      controlled trial including 56 infertile patients undergoing hysterosalpingography
      was performed. After a hysterosalpingogram with water-soluble contrast
      demonstrated tubal patency, 30 patients were randomized to receive oil-soluble
      contrast medium (oil group) and 26 patients received no additional contrast
      medium (control group). The outcome was pregnancy and timing of pregnancy in
      relation to hysterosalpingography. There were 18 (64%) pregnancies in the oil
      group and 14 (56%) pregnancies in the control group. Mean time to achieve
      pregnancy was shorter in the oil group: 3.8 months in the oil group compared with
      6.1 months in the control group (P =.06) There was a clinically meaningful
      improvement in pregnancy rates between the oil group and the control group at 1
      month postprocedure (relative risk [RR] 2.1, 95% confidence interval [CI] 0.6,
      7.2). However, at 12 months postprocedure, the advantage was diminished. (RR 1.3,
      CI 0.8, 2.1)Eighteen months after hysterosalpingography, contrast does not appear
      to influence cumulative pregnancy rates; however, the addition of oil-soluble
      contrast medium to water-soluble contrast medium may have the potential to reduce
      the time to conception.

PMID- 12517655
TI  - Physician specialty is significantly associated with hormone replacement therapy
      use.
AB  - OBJECTIVE: To compare the characteristics of postmenopausal women seen by
      gynecologists versus family physicians and to determine factors associated with
      current hormone replacement therapy (HRT) use. METHODS: We conducted a cross
      sectional study of 426 postmenopausal women seen for their annual examination at
      university clinics. Logistic regression was used to identify predictors of
      current versus never HRT use. RESULTS: Overall, 60% of women recruited in family
      practice clinics and 69% in gynecology clinics were current HRT users.
      Significant, positive, multivariable predictors of HRT use were gynecology versus
      family practice clinic attendance (odds ratio [OR] 2.6, 95% confidence interval
      [CI] 1.4, 4.6), surgical menopause (OR 2.3, 95% CI 1.2, 4.6), history of
      depression (OR 2.3, 95% CI 1.2, 4.7), at least two live births (OR 2.1, 95% CI
      1.1, 4.0), and current alcohol use (OR 1.8, 95% CI 1.04, 3.2). Significant,
      negative, multivariable predictors were increasing age (60-70 years versus less
      than 60 years, OR 0.4, 95% CI 0.2, 0.8; 70 years or older versus less than 60
      years, OR 0.4, 95% CI 0.2, 0.9) and history of breast cancer (OR 0.04, 95% CI
      0.01, 0.14). Sociodemographic factors, smoking status, number of self-reported
      medical conditions, number of prescription medications besides HRT, oral
      contraceptive use, history of hypertension, and exercise level were tested as
      covariates and did not enter the model. CONCLUSION: Although current HRT use
      rates between clinics were similar and higher than national averages, we found
      that the adjusted odds of current HRT use among women receiving care from
      gynecologists was 2.6 times that among women receiving care from family
      physicians. This practice variation may reflect physicians' uncertainty
      surrounding the preventive value of HRT.

PMID- 12517656
TI  - The preterm labor index and fetal fibronectin for prediction of preterm delivery
      with intact membranes.
AB  - OBJECTIVE: To compare the preterm labor index with the biochemical marker fetal
      fibronectin in predicting preterm delivery. METHODS: In 185 women with preterm
      labor and intact membranes, the preterm labor index was determined based on
      clinical findings of uterine contractions, bleeding, and cervical dilatation. An
      immunosorbent assay was used to measure oncofetal fibronectin. RESULTS: A
      significant negative correlation was noted between the preterm labor index and
      the interval from hospitalization to delivery. Based on a receiver operating
      characteristic curve, a preterm labor index 4 or higher was defined as positive.
      Rates of preterm delivery overall and of delivery within 1 week in the preterm
      labor index-negative group were 55.2% and 13.8%, respectively. Those in the
      preterm labor index-positive group were significantly higher (88.4% and 56.5%).
      With respect to predicting when a delivery would occur during the first week of
      hospitalization, the preterm labor index and fetal fibronectin did not differ in
      sensitivity (77.7% and 73.8%, respectively), specificity (79.5% and 74.2%),
      positive predictive value (66.7% and 60.8%), or negative predictive value (84.5%
      and 83.9%). However, within the preterm labor index-negative group, the rates of
      preterm delivery (68.4%), delivery within 1 week (28.9%), and neonatal treatment
      in an intensive care unit (36.8%) were significantly higher in fetal fibronectin
      positive than in fibronectin-negative cases (46.2%, 9.0%, and 10.3%,
      respectively). CONCLUSION: The preterm labor index was similar to the fetal
      fibronectin assay in its ability to predict preterm delivery.

PMID- 12517657
TI  - The changing epidemiology of multiple births in the United States.
AB  - OBJECTIVE: To describe changes in the epidemiology of multiple births in the
      United States from 1980 to 1999 by race, maternal age, and region; and to examine
      the impact of these changes on birth weight-specific infant mortality rates for
      singleton and multiple births. METHODS: Retrospective univariate and
      multivariable analyses were conducted using vital statistics data from the
      National Center for Health Statistics. RESULTS: Between 1980 and 1999, the
      overall multiple birth ratio increased 59% (from 19.3 to 30.7 multiple births per
      1000 live births, P <.001), with rates among whites increasing more rapidly than
      among blacks. Women of advanced maternal age, especially those aged 30-34, 35-39,
      and 40-44 experienced the greatest increases (62%, 81%, and 110%, respectively).
      Although all regions of the United States experienced increases in multiple birth
      ratios between 1991 and 1999, the Northeast had the highest twin (33.9 per 1000
      live births) and higher order birth ratios (280.5 per 100,000 live births), even
      after adjusting for maternal age and race. Between 1989 and 1999, multiple births
      experienced greater declines in infant mortality than singletons in all birth
      weight categories. Consequently, very low birth weight and moderately low birth
      weight infant mortality rates among multiples were lower than among singletons.
      CONCLUSION: It is important to understand the changing epidemiology of multiple
      births, especially for women at highest risk (advanced maternal age, white race,
      Northeast residents). The attribution of infertility management requires further
      study. The differential birth weight-specific infant mortality for singletons and
      multiples demonstrates the importance of stratifying by plurality when assessing
      perinatal outcomes.

PMID- 12517658
TI  - Post-cesarean delivery fever and uterine rupture in a subsequent trial of labor.
AB  - OBJECTIVE: To evaluate the association of uterine rupture during a trial of labor
      after cesarean with postpartum fever after the prior cesarean delivery. METHODS:
      We conducted a nested, case-control study in a cohort of all women undergoing a
      trial of labor after cesarean over a 12-year period in a single tertiary care
      institution. The current study was limited to all women undergoing a trial of
      labor after cesarean at term with a symptomatic uterine rupture and who also had
      their prior cesarean at the same institution. Four controls, who all had their
      prior cesarean at the same institution, were matched to each case by year of
      delivery, number of prior cesareans, prior vaginal delivery, and induction in the
      index pregnancy. Medical records were reviewed for maximum postpartum temperature
      for the previous cesarean. Fever was defined as a temperature above 38C.
      Conditional logistic regression analysis was performed taking into account
      potential confounding factors. RESULTS: There were 21 cases of uterine rupture
      included in the analysis. The rate of fever following the prior cesarean was 38%
      (8/21) among the cases, and 15% (13/84) in the controls, P =.03. Multiple
      logistic regression analysis examining the association of uterine rupture and
      postpartum fever adjusting for confounders revealed an odds ratio of 4.0, 95%
      confidence interval 1.0, 15.5. CONCLUSION: Postpartum fever after cesarean
      delivery is associated with an increased risk of uterine rupture during a
      subsequent trial of labor.

PMID- 12517659
TI  - Fluctuations of maternal smoking during pregnancy.
AB  - To examine fluctuations in women's cigarette smoking during pregnancy and
      implications for the design of clinical interventions for pregnant smokers and
      research on the effects of fetal exposure to cigarettes. We examined changes in
      absolute smoking status in 1426 women who reportedly smoked during their last
      pregnancy in the National Health Interview Survey 1991 Pregnancy and Smoking
      Supplement and fluctuations in amount smoked in 60 pregnant smokers in the Family
      Health and Development Project. In the National Health Interview Survey 1991
      Pregnancy and Smoking Supplement, a substantial proportion of women exhibited a
      pattern of repeated cessation and relapse. In multivariable logistic regression
      models, having more than a high school education was significantly associated
      with being an intermittent versus a continuous smoker (odds ratio = 1.55, P <.01)
      and with successful quitting versus continuously smoking or relapsing (odds ratio
      = 1.74, P <.01). Fluctuations in smoking intensity in the Family Health and
      Development Project were also substantial and, although 48% quit or reduced their
      smoking upon learning of their pregnancy, over half changed smoking intensity
      multiple times. We conclude that smoking during pregnancy is a complex and
      variable behavior for many women. Simple measures of smoking may lead to under
      estimation of the impact of smoking on the fetus, and brief smoking cessation
      interventions early in pregnancy are likely to be inadequate for many smokers
      during pregnancy.

PMID- 12517660
TI  - Urinary incontinence and depression in middle-aged United States women.
AB  - OBJECTIVE: To determine the correlates of incontinence in middle-aged women and
      to test for an association between incontinence and depression. METHODS: This was
      a population-based cross-sectional study of 5701 women who were residents of the
      United States, aged 50-69 years, and participated in the third interview of the
      Health and Retirement Study. The primary outcome measure was self-reported
      urinary incontinence. Depression was ascertained based on criteria set by the
      Diagnostic and Statistical Manual of Mental Disorders, using a short form of the
      Composite International Diagnostic Interview. In addition, depressive symptoms
      were assessed using the revised Center for Epidemiologic Studies Depression
      Scale. Multivariable logistic regression models were constructed to determine the
      independent association between incontinence and depression, after adjusting for
      confounders. RESULTS: Approximately 16% reported either mild-moderate or severe
      incontinence. Depression, race, age, body mass index, medical comorbidities, and
      limited activities of daily living were associated with incontinence. After
      adjusting for medical morbidity, functional status, and demographic variables,
      women with severe and mild-moderate incontinence were 80% (odds ratio [OR] 1.82;
      95% confidence interval [CI] 1.26, 2.63) and 40% (OR 1.41; 95% CI 1.06, 1.87)
      more likely, respectively, to have depression than continent women. The
      association did not hold for depressive symptoms measured by the revised Center
      for Epidemiologic Studies Depression Scale after adjusting for covariates.
      CONCLUSION: Depression and incontinence are associated in middle-aged women. The
      strength of the association depends on the instrument used to classify
      depression. This reinforces the need to screen patients presenting for treatment
      of urinary incontinence for depression.

PMID- 12517661
TI  - Venous thromboembolism prophylaxis: patients at high risk to fail intermittent
      pneumatic compression.
AB  - To identify patients who fail intermittent pneumatic compression and who might be
      considered for other more intense thromboembolic prophylaxis.We conducted a
      retrospective review of consecutive gynecologic surgery patients treated with
      intermittent pneumatic compression. Risk factors associated with thromboemboli
      and demographic data were reviewed. Clinical suspicion of thromboemboli was
      confirmed by established diagnostic techniques such as duplex Doppler ultrasound
      and ventilation perfusion scanning. The association between individual risk
      factors and the incidence of thromboemboli was identified. To control for
      confounding of variables, multivariable stepwise logistic regression analysis was
      performed.A total of 1862 patients undergoing gynecologic surgery between 1996
      and 1997 were treated perioperatively with intermittent pneumatic compression.
      The overall incidence of postoperative thromboemboli was 1.3% (15 cases of
      clinically significant postoperative pulmonary emboli and nine deep venous
      thrombosis). Risk factors associated with the occurrence of thromboemboli were:
      cancer (P =.001), history of deep venous thrombosis (P =.03), hypertension (P
      =.05), use of antihypertensives (P =.04), and age at least 60 years (P =.002).
      Intraoperative risk factors included duration of anesthesia more than 3 hours (P
      =.05). The multivariable regression analysis found that the diagnosis of cancer
      (P =.001), history of deep venous thrombosis (P =.006), and age greater than 60
      years (P =.04) were independent prognostic factors. Patients with two or three of
      these variables had a 3.2% incidence of developing thromboemboli as compared with
      a 0.6% incidence of thromboemboli if the patient had none or one risk factor.
      Patients most likely to fail intermittent pneumatic compression prophylaxis
      include those with cancer, a past history of deep venous thrombosis, or who are
      60 years or older. This information identifies a "higher-risk" group of patients
      who should be considered for more intense prophylaxis programs.

PMID- 12517662
TI  - Left lateral predisposition of endometriosis and endometrioma.
AB  - To evaluate lateral distribution of endometriosis and ovarian endometrioma in
      women with endometriosis. We evaluated operative reports of women who underwent
      laparoscopic treatment of endometriosis (n = 330) and ovarian endometrioma (n =
      185) from January 1996 to January 2002. Data on all operative findings consisted
      of a written report, a diagram, the revised American Fertility Society
      classification of endometriosis, and a printout of the dictated report.
      Endometriotic implants were confined to one side of the pelvis in 143 women and
      bilaterally in 187 others. Endometriosis was significantly more frequent in the
      left (64.3%) than in the right hemipelvis (P <.001, odds ratio 3.3, 95%
      confidence interval 2.0, 5.3). Of those with bilateral lesions, adhesions were
      also more frequently found on the left than on the right hemipelvis (16.6% versus
      6.9%, P <.01, odds ratio 2.6, 95% confidence interval 1.3, 5.2). Endometrioma was
      found in the left ovary (n = 90), in the right ovary (n = 59), and bilaterally (n
      = 36). Left ovarian endometrioma was found more frequently (60.4%) than right
      endometrioma (P <.001, odds ratio 2.3, 95% confidence interval 1.5, 3.7). This
      trend was not related to the size of the endometrioma.Our results confirm a left
      lateral predisposition of endometriosis and ovarian endometrioma. It is possible
      that this is related to decreased fluid movement in the left side of the pelvis
      because of the presence of sigmoid colon. These findings may support the theory
      that the origin of endometriosis is from the regurgitated endometrial cells.

PMID- 12517663
TI  - Effects of a depression education program on residents' knowledge, attitudes, and
      clinical skills.
AB  - OBJECTIVE: To determine whether an interactive educational program would improve
      obstetrics and gynecology residents' knowledge, attitudes, confidence, and skills
      in caring for depressed patients. METHODS: We recruited 74 residents from eight
      residency programs to attend the Depression Education Program, which consists of
      a 1-hour lecture and two 2-hour workshops combining discussion, diagnosis and
      treatment tools, critique of a videotape, practice with feedback, and audiotape
      self-assessment. Before and after the program, participants 1) completed a
      questionnaire measuring knowledge, attitudes, and reported actions taken with a
      recent depressed patient; 2) received a standardized patient visit; and 3) kept
      lists of patients they suspected were depressed. Clinic patients completed a
      depression screening questionnaire. To assess improvement, we used paired t
      tests, McNemar chi2 tests, and multivariate models adjusting for training site.
      RESULTS: The education program led to 3-month improvements in participants'
      reported use of formal diagnostic criteria (38% before, 66% after; P =.004),
      clinical actions documented for suspected depression (P =.035), and perceived
      self-efficacy in depression care (P <.001). Perceived preparedness to diagnose
      depression, treat with medications, and comanage with a mental health
      practitioner improved (P <.05 for each). Small improvements in clinical behaviors
      with standardized patients and clinic-based depression detection rates were not
      statistically significant. CONCLUSION: The Depression Education Program improved
      residents' knowledge, confidence, and reported clinical actions with depressed
      patients, but did not improve most objectively assessed outcomes.

PMID- 12517664
TI  - International terminology of colposcopy: an updated report from the International
      Federation for Cervical Pathology and Colposcopy.

PMID- 12517666
TI  - Outcomes of planned home births in Washington State: 1989-1996.

PMID- 12517665
TI  - Preterm premature rupture of the membranes.
AB  - Preterm premature rupture of membranes (PROM) affects over 120,000 pregnancies
      annually in the United States and is associated with significant maternal, fetal,
      and neonatal risk. Management of PROM requires an accurate diagnosis as well as
      evaluation of the risks and benefits of continued pregnancy or expeditious
      delivery. An understanding of gestational age-dependent neonatal morbidity and
      mortality is important in determining the potential benefits of conservative
      management of preterm PROM at any gestation. Where possible, the treatment of
      pregnancies complicated by PROM remote from term should be directed towards
      conserving the pregnancy and reducing perinatal morbidity due to prematurity
      while monitoring closely for evidence of infection, placental abruption, labor,
      or fetal compromise due to umbilical cord compression. Current evidence suggests
      aggressive adjunctive antibiotic therapy to reduce gestational age-dependent and
      infectious infant morbidity. Similarly, review of evaluable data indicates that
      antenatal corticosteroid administration in this setting enhances neonatal outcome
      without increasing the risk of perinatal infection. It is not clear that
      tocolysis in the setting of preterm PROM remote from term reduces infant
      morbidity. When preterm PROM occurs near term, particularly if fetal pulmonary
      maturity is evident, the patient is generally best served by expeditious
      delivery.

PMID- 12517667
TI  - Presumed diagnosis of ectopic pregnancy.

PMID- 12517668
TI  - Presumed diagnosis of ectopic pregnancy.

PMID- 12517670
TI  - Reappraisal of neonatal clavicular fracture: relationship between infant size and
      neonatal mortality.

PMID- 12517672
TI  - Neonatal organ system injury in acute birth asphyxia sufficient to result in
      neonatal encephalopathy.

PMID- 12517674
TI  - ACOG Committee Opinion. Immunization during pregnancy.

PMID- 12517675
TI  - Reduction of pressor response to vasoconstrictor agents by overexpression of
      catalase in mice.
AB  - BACKGROUND: Hydrogen peroxide (H(2)O(2)) has been shown to induce vascular smooth
      muscle cell contraction in vitro. In this study, the effect of endogenously
      produced H(2)O(2) on blood pressure (BP) was examined using a transgenic mouse
      model (hCatTg(+/0)) in which catalase is overexpressed. METHODS: The hCatTg(+/0)
      and wild-type mice received a bolus injection of norepinephrine (NE; 1 microg/g)
      or angiotensin II (Ang II; 0.5 microg/g), or an osmotic minipump infusion of NE
      (2.5 microg/g/day) or Ang II (0.5 microg/g/day) for 7 days. Systolic BP (SBP) was
      measured using a tail-cuff apparatus. H(2)O(2) release from mouse aortas was
      measured using an H(2)O(2) assay kit. RESULTS: The hCatTg(+/0) and wild-type mice
      showed similar basal levels of systolic BP (SBP) and H(2)O(2) release from the
      aorta. A bolus injection of NE or Ang II increased SBP 31 +/- 5 and 37 +/- 6 mm
      Hg, respectively, in wild-type mice. In contrast, same doses of NE and Ang II
      increased SBP only 15 +/- 3 and 17 +/- 4 mm Hg, respectively, in hCatTg(+/0)
      mice. Osmotic minipump infusion of NE or Ang II increased SBP by approximately 30
      mm Hg in wild-type mice, but only by about 10 mm Hg in hCatTg(+/0) mice. The
      addition of NE or Ang II to the incubation media significantly increased H(2)O(2)
      release from the aortic segment of wild-type mice but did not alter H(2)O(2)
      release from the aortic segment of hCatTg(+/0) mice. CONCLUSION: Overexpression
      of catalase diminishes the pressor response to NE and Ang II by reducing H(2)O(2)
      production in the arterial wall.

PMID- 12517676
TI  - Influence of dietary salt intake on the response of isolated perfused mesenteric
      veins of the dog to vasoactive agents.
AB  - BACKGROUND: Previous work has established that a high dietary salt intake results
      in enhanced arterial vasoconstrictor responses to stimulation with agonists. This
      investigation was designed to investigate the effects of dietary salt on the
      responses of isolated capacitance vessels (third order mesenteric veins).
      METHODS: Dogs were fed diets containing low, intermediate, and high levels of
      dietary salt (0.4, 3.0, and 6.0 mmol kg/day). The animals were killed, and
      lengths of mesenteric vein were mounted in a perfusion myograph with changes in
      lumenal diameter measured using a video tracking device. Responses to cumulative
      doses of norepinephrine (NE) and acetylcholine (Ach) were then determined.
      RESULTS: The vasoconstrictor responses to NE were greater in the veins from dogs
      on a high salt diet. Acetylcholine also caused venoconstriction that also was
      greater in the high salt group of animals. Responses to Ach were unaffected by
      N(omega)-nitro-L-arginine methyl ester but were abolished by atropine.
      CONCLUSIONS: These results indicate that mesenteric veins from dogs fed a high
      salt diet constrict more powerfully in response to agonists, which could
      contribute to the hypertensive effects of high intakes of dietary salt.

PMID- 12517677
TI  - Endothelial damage and angiogenesis in hypertensive patients: relationship to
      cardiovascular risk factors and risk factor management.
AB  - BACKGROUND: Hypertensive patients are at particular risk of cardiovascular
      complications, possibly related to endothelial damage or dysfunction, or to
      abnormal angiogenesis. These pathophysiologic processes are assessable by
      measurement of plasma levels of von Willebrand factor (vWf), and by vascular
      endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). We
      hypothesized that these markers would correlate with the Framingham
      cardiovascular risk score and would be responsive to treatment. METHODS: We
      measured these markers by enzyme-linked immunosorbent assay in 286 patients with
      hypertension (239 men; mean age 63 years; mean systolic blood pressure
      [BP]/diastolic BP 162/89 mm Hg) and additional risk factors, and related them to
      the patient's cardiovascular disease (CVD) and cerebrovascular accident (CVA)
      risk, using the Framingham equation. Patients were compared with 60 healthy
      normotensive controls. In 248 patients, the effects of 6 months of intensified
      cardiovascular risk factor management, including BP and (where appropriate) lipid
      lowering treatment, were investigated. RESULTS: Plasma VEGF and vWf levels were
      higher, but sFlt-1 levels lower (all P <.001), in the hypertensive patients
      compared with the controls. The VEGF and vWf levels correlated significantly with
      age, systolic and diastolic BP, 10-year CVD risk, and CVA risk scores (all P
      <.01), whereas sFlt-1 was negatively correlated with these risk scores (P <.01).
      After intensified cardiovascular risk factor management, total cholesterol, BP,
      VEGF, and vWf levels were all reduced, yet sFlt-1 levels increased (all P <.05).
      CONCLUSIONS: In hypertension, the processes of endothelial damage and
      angiogenesis are abnormal, and correlate with overall cardiovascular risk.
      Indices of endothelial damage and angiogenesis are beneficially changed by
      intensive cardiovascular risk factor management.

PMID- 12517678
TI  - Calcium exerts a larger regulatory effect on potassium+ channels in small
      mesenteric artery mycoytes from spontaneously hypertensive rats compared to
      Wistar-Kyoto rats.
AB  - Hypertension is associated with a remodeling of arterial smooth muscle K(+)
      channels with Ca(2+)-gated K(+) channel (BK(Ca)) activity being enhanced and
      voltage-gated K(+) channel (K(v)) activity depressed. Because both of these
      channel types are modulated by intracellular Ca(2+), we tested the hypothesis
      that Ca(2+) had a larger effect on both BK(Ca) and K(v) channels in arterial
      myocytes from hypertensive animals. Myocytes were enzymatically dispersed from
      small mesenteric arteries (SMA) of 12-week-old Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR). Using whole cell patch clamp methods,
      BK(Ca) and K(v) current components were determined as iberiotoxin-sensitive and 
      insensitive currents, respectively. The effects of Ca(2+) on these K(+) current
      components were determined from measurements made with 0.2 and 2 mmol/L external
      Ca(2+). Increasing external Ca(2+) from 0.2 to 2 mmol/L Ca(2+) increased BK(Ca)
      currents recorded using myocytes from both WKY rats and SHR with a larger effect
      in SHR. Increasing external Ca(2+) decreased K(v) currents recorded using
      myocytes from both WKY and SHR also with a larger effect in SHR. In other
      experiments, currents through voltage-gated Ca(2+) channels (Ca(v)) measured at
      0.2 mmol/L external Ca(2+) were 12 +/- 2% (n = 12) of those recorded at 2 mmol/L
      Ca(2+) with no differences in percent effect between WKY and SHR. In isolated SMA
      segments, isometric force development in response to 140 mmol/L KCl at 0.2 mmol/L
      external Ca(2+) was about 23 +/- 6% (n = 8) of that measured at 2 mmol/L external
      Ca(2+). These results suggest that an increase in Ca(2+) influx through Ca(v) or
      in intracellular Ca(2+) secondary to an increase in external Ca(2+) augments
      BK(Ca) currents and inhibits K(v) currents in SMA myocytes with a larger effect
      in SHR compared to WKY. This mechanism may contribute to the functional
      remodeling of K(+) currents of arterial myocytes in hypertensive animals.

PMID- 12517679
TI  - Influence of nitric oxide on neurogenic contraction and relaxation of the human
      gastroepiploic artery.
AB  - BACKGROUND: The objective of this study was to characterize the neurogenic
      contraction and relaxation of the human gastroepiploic artery and to determine
      whether the responses are mediated by nitric oxide (NO) from neural or
      endothelial origin. METHODS: Rings of human gastroepiploic artery were obtained
      from 18 patients (12 men, 6 women) undergoing gastrectomy. The rings were
      suspended in organ baths for isometric recording of tension. We studied the
      contractile and relaxant responses to electrical field stimulation. RESULTS: In
      arteries under resting conditions, electrical field stimulation (2 to 8 Hz)
      caused frequency-dependent contractions that were of greater magnitude in
      arteries denuded of endothelium and blocked by tetrodotoxin (10(-6) mol/L). The
      inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L)
      increased contractile responses only in arteries with endothelium. In
      preparations contracted with norepinephrine in the presence of guanethidine (10(
      6) mol/L) and atropine (10(-6) mol/L), electrical stimulation induced frequency
      dependent relaxations. This neurogenic relaxation was prevented by L-NMMA (10(-4)
      mol/L) and tetrodotoxin (10(-6) mol/L), but was unaffected by removal of the
      endothelium. CONCLUSIONS: The results provide functional evidence that NO is
      released by autonomic nerves of the human gastroepiploic artery. We hypothesize
      that the release of NO from both endothelial and neurogenic origin may modulate
      resistance of the human gastroepiploic artery. Dysfunction in any of these
      sources of NO should be considered in some form of vasospasm.

PMID- 12517680
TI  - Effects of omapatrilat on blood pressure and renal injury in L-NAME and L-NAME
      plus DOCA-treated rats.
AB  - BACKGROUND: This study investigates the effects of chronic administration of
      omapatrilat (OMA) on blood pressure (BP), renal injury, and other variables in
      N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension and in the low-renin
      model produced by the simultaneous administration of L-NAME and
      deoxycorticosterone acetate (DOCA). METHODS: The control, DOCA, L-NAME, L-NAME +
      DOCA, L-NAME + OMA, and L-NAME + DOCA + OMA groups were used. Tail systolic BP
      was measured twice a week. After 4 weeks of treatment, mean arterial pressure
      (MAP), and metabolic, morphologic, and renal variables were measured. RESULTS:
      The final values of MAP were 109 +/- 5.1 mm Hg for the control group, 113 +/- 3.0
      mm Hg for DOCA, 175 +/- 3.7 mm Hg for L-NAME, 193 +/- 3.8 mm Hg for L-NAME +
      DOCA, 117 +/- 3.9 mm Hg for L-NAME + OMA, and 158 +/- 3.0 mm Hg for L-NAME + DOCA
      + OMA. The rats treated with L-NAME showed mild and scarce renal lesions, which
      were prevented by OMA treatment and the L-NAME + DOCA group showed proteinuria
      and hyaline arteriopathy, which were markedly attenuated in the L-NAME + DOCA +
      OMA group. Plasma urea and creatinine were significantly increased in the L-NAME
      + DOCA group, whereas these variables were not significantly greater in the L
      NAME + DOCA + OMA group versus controls. The L-NAME + DOCA group showed relative
      renal and cardiac hypertrophy that was not observed in the L-NAME + DOCA + OMA
      group. CONCLUSIONS: The simultaneous blockade of neutral endopeptidase (NEP) and
      angiotensin converting enzyme (ACE) completely prevents L-NAME hypertension. Our
      results also show that OMA attenuates the increased BP and the renal injury in L
      NAME hypertensive rats treated with DOCA. Assuming that this is a low-renin model
      of hypertension, the protective effect of OMA may be due to an increase in
      vasodilator peptides produced by both ACE and NEP inhibition.

PMID- 12517681
TI  - Short-term predictors of maintenance of normotension after withdrawal of
      antihypertensive drugs in the second Australian National Blood Pressure Study
      (ANBP2).
AB  - BACKGROUND: Antihypertensive drug therapy is considered lifelong but in the
      family practice environment drug cessation may provide an opportunity to attempt
      nonpharmacologic strategies for blood pressure (BP) control with a clear outcome,
      maintaining drug-free status. The identification of simple predictors would
      assist the family physician to select who may or may not have their medication
      ceased. METHODS: To monitor a drug cessation program in currently treated
      hypertensive patients in Australian family practice, 25,826 patients aged 65 to
      84 years currently receiving antihypertensive medication, were offered drug
      withdrawal as part of the run-in phase of a large clinical trial. Outcomes
      investigated were the proportion of patients completing drug withdrawal and
      maintaining short-term BP control and factors that predicted these patients.
      RESULTS: A total of 18,993 patients did not enter the withdrawal program; 6291
      (92% of those who entered) completed drug withdrawal. In comparison to patients
      who did not complete drug withdrawal, they were younger and more likely male. A
      total of 1,228 (18% of those who entered) ceased medication and maintained
      adequate BP control for 0 to 76 weeks (median, 4 weeks). Cox regression analysis
      identified lower on therapy systolic and diastolic BP, younger age, type of
      agent, and monotherapy as predictors of successful drug withdrawal and
      maintenance of BP control. CONCLUSIONS: Cessation of antihypertensive drug
      therapy is possible in a substantial proportion (18%) of patients attending
      family practice who are willing to do so and is most successful in those who are
      younger with BP controlled on monotherapy. Where this strategy is initiated, use
      of such predictors, effective behavioral change, and systematic follow-up is
      recommended.

PMID- 12517682
TI  - Different drug classes have variable effects on blood pressure depending on the
      time of day.
AB  - BACKGROUND: Blood pressure (BP) is controlled by a variety of systems, the
      activities of which vary throughout the day. As drugs are developed that
      selectively block these systems, the fall in BP may not be consistent over 24 h.
      METHODS: A total of 24 patients (aged >65 years) with systolic BP (SBP; >150 mm
      Hg) that had not been treated entered a substudy of a larger study performed in
      74 patients. In a double blind, crossover study with a balanced design, they
      received placebo, atenolol 50 mg, perindopril 8 mg, felodipine 10 mg, or
      hydrochlorothiazide 50 mg. The study periods were 2 months. Ambulatory BP
      monitoring was performed at the end of each period, and was divided into awake
      periods (9:00 AM to 10:00 PM), sleep periods (12:00 AM to 6:00 AM), and morning
      periods (6:00 AM to 9:00 AM). Medication was taken at 9:00 AM. RESULTS: The four
      drug classes lowered 24-h mean SBP (P <.05), but the fall with atenolol was less
      than with the other drugs. The fall in awake BP with perindopril was less than
      with felodipine or hydrochlorothiazide. Atenolol caused no significant fall in
      sleep or morning SBP, and the falls with the other three drugs were significant
      and were greater than the fall with atenolol. The fall in sleep BP with
      perindopril was greater than with the other drug classes. The awake-sleep
      difference in SBP increased with perindopril, stayed the same with felodipine and
      hydrochlorothiazide, and was reduced by atenolol. CONCLUSIONS: In this study, the
      response to the different drug classes differed. The response to drugs that work
      relatively nonspecifically (diuretics, calcium blockers) was relatively
      consistent over 24 h. The response to beta blockers and to angiotensin converting
      enzyme inhibitors reflected the activity of control systems. This finding
      supports the concept of multiple drug therapy that may need to be tailored to the
      time of day.

PMID- 12517683
TI  - Efficacy and safety of a once daily graded-release diltiazem formulation in
      essential hypertension.
AB  - BACKGROUND: The efficacy and safety of a chronotherapeutic, graded-release
      diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose
      administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized,
      double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8
      AM in 478 patients with moderate-to-severe essential hypertension. METHODS: We
      assessed the change from baseline to end point in trough diastolic blood pressure
      (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM
      and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM). RESULTS: Bedtime
      doses of GRD showed dose-related mean reductions in trough DBP that were
      significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated
      with a significantly greater reduction in mean DBP between 6 AM and 12 noon
      compared to morning GRD 360 mg with a least squares mean for treatment difference
      of -3.3 mm Hg (P =.0004). Similar dose-related and significant reductions in
      systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events
      (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo
      group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to
      that observed for the 240-mg group (42.6%). CONCLUSIONS: The GRD dose-dependently
      significantly reduces BP and HR over the 24-h interval after once-daily bedtime
      dosing. Further greater reductions were obtained between 6 AM and 12 noon, when
      circadian BP is highest, compared to morning administration of the same dose. The
      540-mg GRD was safe, well tolerated, and offers further therapeutic option for
      patients with severe hypertension who required additional BP control.

PMID- 12517684
TI  - Detection of a receptor for angiotensinogen on placental cells.
AB  - BACKGROUND: Current evidence indicates that there may be a tissue-specific renin
      angiotensin system (RAS) in the human placenta. To better define the placental
      RAS, this study sought to determine whether placental derived cells possessed a
      receptor for angiotensinogen (AGT), a rate limiting component of the RAS.
      METHODS: A human placenta-derived cell line, CRL-7548, a highly purified AGT and
      iodine-125-labeled angiotensinogen ((125)I-AGT) were used in this study. The
      cells were seeded in 35-mm diameter plastic wells, cultured for 2 days in fetal
      bovine serum-Dulbecco's modified Eagle's medium to reach about 80% to 90%
      confluence, 2 x 10(4) cells/well and passed in Dulbecco's modified Eagle's medium
      free of fetal bovine serum before experimentation. A quantity of 3 microg of
      (125)I-AGT was added to each well at zero time. RESULTS: The cells rapidly bound
      (125)I-AGT in a time dependent manner with saturation being achieved in 2 to 4 h.
      This binding was competitively inhibited by unlabeled AGT. Prior addition of a
      100-fold excess of unlabeled AGT resulted in a 54% decrease in maximal binding.
      Bound AGT was also competitively displaced by AGT. Addition of a 200-fold excess
      of unlabeled AGT displaced 70% of the bound (125)I-AGT. Thus, approximately 30%
      of the total binding can be attributed to nonspecific binding. An acid wash (0.2
      mol/L acetic acid, 0.5 mol/L NaCl, pH 2.5) at 4 degrees C removed 46% of the
      bound (125)I-AGT. An acid wash is known to dissociate cell surface ligand
      receptor complexes, but does not remove internalized ligand. CONCLUSION: The
      results of this study provide evidence for the existence of an AGT receptor on
      placenta-derived cells. This is the first report of an AGT receptor.

PMID- 12517685
TI  - Caffeine increases aortic stiffness in hypertensive patients.
AB  - BACKGROUND: Caffeine is the most widely used pharmacologic substance. Aortic
      stiffness is an important factor for cardiovascular system performance and a
      prognosticator of cardiovascular risk. We investigated the effect of caffeine on
      aortic stiffness in treated hypertensive patients. METHODS: We studied the effect
      of caffeine (250 mg) in 12 treated hypertensive patients according to a
      randomized, placebo-controlled, double-blind, cross-over design during a 3-h
      period. Aortic stiffness was evaluated by carotid-femoral pulse wave velocity.
      RESULTS: Systolic blood pressure (BP) and pulse pressure increased significantly
      throughout the study (by 12.3 and 7.4 mm Hg, P =.005 and P <.01, respectively),
      whereas diastolic BP did not change. Pulse wave velocity increased (by 0.57
      m/sec, P <.05) denoting an increase in aortic stiffness. This effect of caffeine
      lasted throughout the study (3 h), peaking at 60 min and decreasing progressively
      thereafter. CONCLUSIONS: These results demonstrate, for the first time, that
      caffeine exerts an acute unfavorable effect on aortic stiffness in treated
      hypertensive patients. This finding has important implications for the impact of
      caffeine consumption on cardiovascular risk in hypertension.

PMID- 12517686
TI  - Hemodynamic effects of nicotinic acid infusion in normotensive and hypertensive
      subjects.
AB  - Nicotonic acid (NA) infusions are associated with peripheral vasodilation from
      the generation of vascular prostaglandins with minimal effects on blood pressure
      (BP) in normotensive subjects. We studied the effects of a NA infusion in 10
      hypertensive and 11 normotensive individuals to further characterize systemic
      hemodynamic responses to NA using pulse waveform analysis. Blood pressure, stroke
      volume, cardiac output, total peripheral resistance, large and small artery
      elasticity were determined before and after a 1-h NA infusion. In the
      normotensives, systolic, diastolic, mean BP, and pulse pressure were not affected
      by NA. In contrast, the hypertensive subjects experienced a decrease in mean BP
      from 105 +/- 2 mm Hg to 100 +/- 3 mm Hg (P <.01) accompanied by significant
      decreases in systolic, diastolic, and pulse pressures. The differential BP
      response occurred despite comparable increases in heart rate (11% to 13%, P
      </=.05) and similar decreases in total peripheral resistance (6%, P </=.05) in
      both groups. However, the normotensive group demonstrated a decrease in overall
      vascular compliance, measured as stroke volume to pulse pressure ratio, from 2.12
      +/- 0.09 to 1.93 +/- 0.09 mL/mm Hg (P <.05). This finding was supported by a
      decrease in C1 (large artery compliance), assessed by pulse waveform analysis,
      from 15.8 +/- 1 to 14.2 +/- 1 mL/mm Hg (P <.05). In contrast, overall compliance
      and C1 were unchanged after the NA infusion in the hypertensive group. These
      results suggest that there is a differential hemodynamic response to NA infusion
      in normotensive and hypertensive individuals. The adjustment in vascular
      compliance may be an important factor in determining overall BP response to NA.

PMID- 12517687
TI  - Decreased plasma adiponectin concentration in patients with essential
      hypertension.
AB  - Adipocytes secrete several biologically active substances that are presumed to be
      involved in obesity-related hypertension. There are no reports that deal with the
      relationship between plasma adiponectin concentration and blood pressure (BP). To
      evaluate the role of adiponectin in essential hypertension 33 patients with
      essential hypertensive (EHP) (12 women, 21 men) and 33 body mass index-matched
      normotensive healthy subjects (NHS) (13 women, 20 men) were studied. In EHP
      plasma adiponectin concentration was significantly lower than in NHS (9.1 +/- 4.5
      v 13.7 +/- 5.2 microg/mL, respectively). In all subjects a significant negative
      correlation was found between plasma adiponectin concentration and mean,
      systolic, and diastolic BP, suggesting that adiponectin contributes to the
      clinical course of essential hypertension.

PMID- 12517688
TI  - Gestational age and birth weight in relation to aortic stiffness in healthy young
      adults: two separate mechanisms?
AB  - BACKGROUND: Impaired vascular development due to intrauterine growth retardation
      and postnatal-induced vascular damage by an unfavorable cardiovascular risk
      profile may both cause stiffer arteries in later decades. METHODS: Of 524 young
      adults, participating in the Atherosclerosis Risk in Young Adults (ARYA) study,
      data on birth characteristics were obtained from the original medical records of
      the Municipal Health Service and the extent of aortic stiffness was assessed
      using carotid-femoral pulse wave velocity (PWV). RESULTS: The PWV showed an
      inverse trend with gestational age (linear regression coefficient (beta) = -0.07
      m/sec per 1 week; P =.064) whereas it was positively related to birth weight
      (beta = 0.33 m/sec per 1 kg; P =.020), adjusted for blood pressure (BP), gender,
      age, and each other. After exclusion of the 26 prematurely born infants, the
      association with gestational age was attenuated (beta = -0.03 m/sec per 1 week; P
      =.582), whereas the relation with birth weight hardly changed (beta = 0.30 m/sec
      per 1 kg; P =.041). In an analysis in which we excluded the 26 subjects with
      diabetic mothers the birth weight-PWV relation was attenuated (beta = 0.21 m/sec
      per 1 kg; P =.169). CONCLUSIONS: Our findings suggest that prematurity drives the
      relation of gestational age and PWV, whereas risk of impaired glucose tolerance
      drives the relation of birth weight and PWV. We hypothesized that two separate
      mechanisms might be involved in the development of arterial stiffness in healthy
      young adults.

PMID- 12517689
TI  - Aldosterone-induced cardiac damage: focus on blood pressure independent effects.
AB  - Mineralocorticoid receptor (MR) antagonists have been used as potassium-sparing
      diuretics in hypertension. However, in addition to their diuretic and secondary
      blood pressure (BP)-lowering effects, there exists strong evidence from clinical
      and experimental studies that they prevent aldosterone-induced myocardial
      fibrosis independent of their effect on BP. Sustained elevation of aldosterone
      levels and increased sodium intake in animal models has been found to induce
      myocardial fibrosis. Fibrosis of the right ventricle, the atria, and the
      pulmonary artery supports the concept that these effects are BP independent,
      corroborated by the finding that spironolactone in a dosage not sufficient to
      lower BP prevents myocardial fibrosis. Patients suffering from primary
      hyperaldosteronism or Conn's adenoma show more myocardial fibrosis, as assessed
      by echocardiography, than essential hypertensive patients. Several mechanisms
      have been proposed to mediate the profibrotic effects of aldosterone, including
      the possibility of local aldosterone production in the heart, an increase of
      myocardial AT(1)-receptor density, and enhanced local angiotensin converting
      enzyme expression. Furthermore, aldosterone increases endothelin receptor
      expression, which also might cause myocardial fibrosis. Because of the pivotal
      importance of aldosterone binding to the MR, MR antagonists have emerged as
      attractive compounds that provide specific end organ protection beyond solely
      their antihypertensive effects.

PMID- 12517690
TI  - When can the practicing physician suspect white coat hypertension? Statement from
      the Working Group on Blood Pressure Monitoring of the European Society of
      Hypertension.

PMID- 12517691
TI  - DASH-sodium trial: where are the data?

PMID- 12517692
TI  - Role of the Na+/Mg2+ exchanger in hypertensions.

PMID- 12517693
TI  - Hyperinsulinemia, intracellular calcium, and membrane function in essential
      hypertension.

PMID- 12517694
TI  - Left ventricular changes in primary aldosteronism.

PMID- 12517695
TI  - Effect of forced titration of nebivolol on response rate in obese hypertensive
      patients.

PMID- 12517696
TI  - Angiotensin II receptor blockade in diabetic nephropathy.

PMID- 12517697
TI  - Cell structure and dynamics.

PMID- 12517698
TI  - Impact of genome-wide functional analyses on cell biology research.
AB  - The availability of complete genome sequences for a variety of organisms, coupled
      with novel approaches that allow evaluation of the functions of thousands of
      genes in parallel, have the potential to greatly impact on cell biology research.
      Functional genomic approaches in Saccharomyces cerevisiae are beginning to make
      significant contributions to the understanding of complex biological systems.

PMID- 12517699
TI  - Structural insights into actin-binding, branching and bundling proteins.
AB  - Structural advances in our understanding of the functions of the actin
      cytoskeleton have come from diverse sources. On the one hand, the determination
      of the structure of a bacterial actin-like protein MreB reveals the prokaryotic
      origins of the actin cytoskeleton, whereas on the other, cryo-electron microscopy
      and crystallography have yielded reconstructions of many actin crosslinking,
      regulatory and binding proteins in complex with F-actin. Not least, a high
      resolution structure of the Arp2/3 complex and a reconstruction with F-actin
      provides considerable insight into the eukaryotic machinery, vital for the
      formation of new F-actin barbed ends, a prerequisite for rapid actin
      polymerisation involved in cell shape change and motility.

PMID- 12517700
TI  - Integration of signals to the Arp2/3 complex.
AB  - The Arp2/3 complex is necessary for nucleating the formation of branched networks
      of actin filaments at the cell cortex, and an increasing number of proteins able
      to activate the Arp2/3 complex have been described. The Wiskott-Aldrich syndrome
      protein (WASP) family and cortactin comprise the large majority of the known
      activators. WASPs bind to Arp2/3 via an acidic (A) domain, and a WH2 domain
      appears to bring an actin monomer to Arp2/3, promoting the nucleation of the new
      filament. Cortactin also binds the Arp2/3 complex via an A domain; however, it
      also binds to actin filaments, which helps activate the Arp2/3 complex and
      stabilise the newly created branches between the filaments.

PMID- 12517701
TI  - Dynamin at the actin-membrane interface.
AB  - Many important cellular processes such as phagocytosis, cell motility and
      endocytosis require the participation of a dynamic and interactive actin
      cytoskeleton that acts to deform cellular membranes. The extensive family of non
      traditional myosins has been implicated in linking the cortical actin gel with
      the plasma membrane. Recently, however, the dynamins have also been included in
      these cell processes as a second family of mechanochemical enzymes that self
      associate and hydrolyze nucleotides to perform 'work' while linking cellular
      membranes to the actin cytoskeleton. The dynamins are believed to form large
      helical polymers from which extend many interactive proline-rich tail domains,
      and these domains bind to a variety of SH3-domain-containing proteins, many of
      which appear to be actin-binding proteins. Recent data support the concept that
      the dynamin family might act as a 'polymeric contractile scaffold' at the
      interface between biological membranes and filamentous actin.

PMID- 12517702
TI  - Microtubules meet substrate adhesions to arrange cell polarity.
AB  - Cell movement is driven by the regulated and polarised turnover of the actin
      cytoskeleton and of the adhesion complexes that link it to the extracellular
      matrix. For most cells, polarisation requires the engagement of microtubules,
      which exert their effect by mediating changes in the activity of the Rho GTPases.
      Evidence suggests that these changes are effected in a very localised fashion at
      sites of substrate adhesion, via specific microtubule-targeting interactions.
      Targeting serves to bring molecular complexes bound at the tips and along
      microtubules in close proximity with adhesion complexes, to promote adhesion
      disassembly and remodelling of the actin cytoskeleton.

PMID- 12517703
TI  - A plus-end raft to control microtubule dynamics and function.
AB  - Cells require a properly oriented and organised microtubule array to transmit
      positional information. Recent data have revealed a heterogeneous population of
      microtubule-binding proteins that accumulates mainly at distal ends of
      polymerising microtubules. Two mechanisms may account for this concentration:
      transient immobilisation, which involves association of proteins with growing
      ends, followed by release more proximally; and deposition at ends via a molecular
      motor. As with lipid rafts, protein concentration at distal ends may allow a
      cascade of interactions in the restricted area of a microtubule plus end. This
      may, in turn, control the dynamic behaviour of this cytoskeletal network and its
      anchoring to other structures.

PMID- 12517704
TI  - Nuclear positioning: the means is at the ends.
AB  - The nucleus, like other smaller organelles in the cell, is dynamic and can move
      about in the cytoplasm. In some cells, nuclear movements are concerned with
      mitosis or meiosis; in others, they are concerned with orienting nuclear
      divisions; and in still others, they deal with distributing nuclei through the
      cytoplasm. Recent interest in nuclear positioning has shown that nuclear
      movements are often mediated by the interactions of dynein and other proteins at
      the plus ends of astral microtubules with the cell cortex. How the microtubule
      minus ends interact with the nucleus also affects nuclear movements.

PMID- 12517705
TI  - The Golgi apparatus at the cell centre.
AB  - In non-polarised mammalian cells, the Golgi apparatus is localised around the
      centrosome and actively maintained there. Microtubules and molecular motor
      activity are required for determining both the localisation and organisation of
      the Golgi apparatus. Other factors, however, also appear necessary for regulating
      both the static steady-state distribution of this organelle and its relationship
      with microtubule minus-end-anchoring activities of the centrosome. Several non
      motor microtubule-binding proteins have now been found to be associated with the
      Golgi apparatus. Recent advances suggest that, in addition to important roles in
      cell motility, polarisation and differentiation, the interplay between Golgi
      apparatus and centrosome could participate in other physiological processes such
      as intracellular signalling, mitosis and apoptosis.

PMID- 12517706
TI  - Cell polarity: Par6, aPKC and cytoskeletal crosstalk.
AB  - Par6 and atypical protein kinase C are key players in the establishment of cell
      polarity. First discovered in Caenorhabditis elegans, the function of this
      protein complex is conserved in all multicellular organisms. Recent work is
      beginning to throw light on how it converts information generated by
      extracellular cues into intracellular asymmetry.

PMID- 12517707
TI  - Control of cell polarity and mitotic spindle positioning in animal cells.
AB  - Cell polarity is an essential feature of many animal cells. It is critical for
      epithelial formation and function, for correct partitioning of fate-determining
      molecules, and for individual cells to chemotax or grow in a defined direction.
      For some of these processes, the position and orientation of the mitotic spindle
      must be coupled to cell polarity for correct positioning of daughter cells and
      inheritance of localised molecules. Recent work in several different systems has
      led to the realisation that similar mechanisms dictate the establishment of
      polarity and subsequent spindle positioning in many animal cells. Microtubules
      and conserved PAR proteins are essential mediators of cell polarity, and mitotic
      spindle positioning depends on heterotrimeric G protein signalling and the
      microtubule motor protein dynein.

PMID- 12517708
TI  - Cytokinesis: relative alignment of the cell division apparatus and the mitotic
      spindle.
AB  - The cell division apparatus is assembled at different stages of the cell cycle in
      different eukaryotic organisms. Mechanisms exist in all organisms, however, to
      ensure that the cell division apparatus and the mitotic spindle are aligned
      perpendicular to each other. Such an alignment ensures that each daughter cell
      receives a nucleus and that the cell division apparatus does not cleave and
      destroy the genetic material. The interaction(s) of astral microtubules with the
      cell cortex appears to play an important role in establishing perpendicularity
      between chromosome segregation and cell division machinery.

PMID- 12517709
TI  - Nuclear envelope dynamics in oocytes: from germinal vesicle breakdown to mitosis.
AB  - We have recently gained new insight into the mechanisms involved in nuclear
      envelope breakdown, the irreversible step that commits a cell to the M phase.
      Results from mammalian cell and starfish oocyte studies suggest that mechanical
      forces of the cytoskeleton, as well as biochemical disassembly of nuclear
      envelope protein complexes, play important roles in this process.

PMID- 12517710
TI  - Basal body/centriole assembly and continuity.
AB  - The long-standing interest in centrioles and basal bodies stems from the
      evolutionary conservation of their structural design and from their dual mode of
      assembly (templated versus de novo), revealed by electron microscopic studies
      nearly four decades ago and unique for a subcellular organelle. Molecular
      dissection of the assembly pathway during the past few years has recently
      progressed, essentially through direct and reverse genetic approaches. These
      studies revealed essential roles for centrins and the gamma-, delta-, epsilon -
      and eta-tubulins in assembly or as specific signals for centriole duplication.
      Identification of further components of basal bodies and centrioles might help to
      unravel the two assembly pathways and their regulation.

PMID- 12517711
TI  - The vertebrate primary cilium is a sensory organelle.
AB  - The primary cilium is a generally non-motile cilium that occurs singly on most
      cells in the vertebrate body. The function of this organelle, which has been the
      subject of much speculation but little experimentation, has been unknown. Recent
      findings reveal that the primary cilium is an antenna displaying specific
      receptors and relaying signals from these receptors to the cell body. For
      example, kidney primary cilia display polycystin-2, which forms part of a Ca2+
      channel that initiates a signal that controls cell differentiation and
      proliferation. Kidney primary cilia also are mechanosensors that, when bent,
      initiate a Ca2+ signal that spreads throughout the cell and to neighboring cells.
      Primary cilia on other cell types specifically display different receptors,
      including those for somatostatin and serotonin.

PMID- 12517712
TI  - Microtubule nucleation.
AB  - Microtubule nucleation is the process in which several tubulin molecules interact
      to form a microtubule seed. Microtubule nucleation occurs spontaneously in
      purified tubulin solutions, and molecular intermediates between tubulin dimers
      and microtubules have been identified. Microtubule nucleation is enhanced in
      tubulin solutions by the addition of gamma-tubulin or various gamma-tubulin
      complexes. In vivo, microtubule assembly is usually seeded by gamma-tubulin ring
      complexes. Recent studies suggest, however, that microtubule nucleation can occur
      in the absence of gamma-tubulin, and that gamma-tubulin may have other cell
      functions apart from being a major component of the gamma-tubulin ring complex.

PMID- 12517713
TI  - Self-organisation and forces in the microtubule cytoskeleton.
AB  - Modern microscopy techniques allow us to observe specifically tagged proteins in
      live cells. We can now see directly that many cellular structures, for example
      mitotic spindles, are in fact dynamic assemblies. Their apparent stability
      results from out-of-equilibrium stochastic interactions at the molecular level.
      Recent studies have shown that the spindles can form even after centrosomes are
      destroyed, and that they can even form around DNA-coated beads devoid of
      kinetochores. Moreover, conditions have been produced in which microtubule asters
      interact even in the absence of chromatin. Together, these observations suggest
      that the spindle can be experimentally deconstructed, and that its defining
      characteristics can be studied in a simplified context, in the absence of the
      full division machinery.

PMID- 12517717
TI  - A subset of caspase substrates functions as the Jekyll and Hyde of apoptosis.
AB  - Cleavage of caspase substrates is believed to be the commitment point that will
      lead a cell towards apoptosis. While the cleavage of some caspase substrates
      participates directly in the dismantling of the cell, others regulate the extent
      of caspase activation. In this communication, we discuss some recent findings
      indicating that two caspase substrates, MEKK1 and RasGAP, change their functions
      from anti- to pro-apoptotic as caspase activity increases. MEKK1 is a MAPK kinase
      kinase regulating the JNK MAPK pathway. As a full-length protein, MEKK1 generates
      protective signals (e.g. in cardiomyocytes), but potentiates apoptosis when
      cleaved by caspases. This switch is mediated by a translocation of the kinase
      activity from insoluble to soluble cellular structures. RasGAP is a regulator of
      Ras GTPase family members. As a full-length protein, RasGAP does not modulate
      apoptosis. However, low caspase activity readily induces the cleavage of RasGAP
      into an N-terminal fragment that generates potent anti-apoptotic signals. At
      higher caspase activity, the N-terminal fragment is further cleaved into two
      fragments that strongly potentiate apoptosis. RasGAP can, thus, be viewed as an 
      apoptostat  because it allows the cells to determine when caspases have been
      mildly activated to fulfill functions other than apoptosis or when caspases are
      strongly activated to mediate apoptosis.

PMID- 12517715
TI  - Losing balance: cytokine signaling and cell death in the context of hepatocyte
      injury and hepatic failure.
AB  - Fulminant hepatic failure (FHF) represents a clinical scenario that is associated
      with high morbidity and mortality, and very limited treatment options. Therefore,
      great efforts have been made recently on defining its biological mechanisms. This
      article gives an overview of the cellular processes that are linked to the loss
      of hepatocytes as a reaction to various agents that cause hepatic failure, and
      summarizes recent results from clinical and experimental studies of the role of
      pro- and antiapoptotic cytokines and their intracellular signaling in this
      context.

PMID- 12517718
TI  - Cytokines in chronic heart failure: possible interaction in the neurohormonal and
      the cytokine system at the cAMP level?
AB  - In recent years, the pathophysiological concept of chronic heart failure (CHF)
      has changed from an isolated hemodynamic view to a more complex concept involving
      neuroendocrine and inflammatory pathways. New therapeutic strategies, such as
      beta-blocker therapy, are based on these new concepts and provide clinical
      evidence for a clinical benefit in patients with CHF. The survival benefit of
      beta-blocker therapy in CHF has been related to neurohumoral regulation. Thus,
      evidence evolved showing that following beta-blocker therapy cytokine levels in
      CHF patients are altered. We have shown that the levels of soluble TNF receptor
      type 2 correlated well with cAMP in leukocytes. Data from clinical studies in
      adult and infant CHF patients have demonstrated that beta-blocker therapy is
      accompanied by altered cytokine, cytokine antagonist, and/or soluble cytokine
      receptor levels. These alterations may result from a dysregulated interaction of
      beta-adrenergic pathways and the cytokine system, and are possibly related to
      cAMP-dependent regulation of the release or shedding of these mediators.

PMID- 12517719
TI  - Activated STAT-1 pathway in the myocardium as a novel therapeutic target in
      ischaemia/reperfusion injury.
AB  - The signal transducers and activators of transcription (STAT) factors function as
      modulators of cytokine signaling and sensors responding to UV and ischaemic
      stress. Recently, we have reported a number of transcriptional mechanisms that
      induce expression of pro-apoptotic genes following ischaemia/reperfusion (I/R) in
      cardiac myocytes. For example, we have shown that STAT-1 plays a role in
      enhancing apoptotic cell death in cardiac myocytes exposed to I/R. In contrast to
      STAT-1, STAT-3, which is activated by the IL-6 cytokine family, has
      cardioprotective effects in cardiac myocytes exposed to I/R. The induction of
      apoptosis in cardiac myocytes by STAT-1 is dependent on STAT-1 phosphorylation on
      serine-727. Furthermore, we have demonstrated that the C-terminal transactivation
      domain of STAT-1 is required to mediate apoptotic cell death in cardiac myocytes
      exposed to I/R. Finally, cardiac myocytes isolated from mice expressing a
      truncated C-terminal STAT-1 were more sensitive to I/R-induced cell death. The
      isolated intact hearts from these animals exposed to I/R injury, had larger
      infarct size and a greater number of TUNEL-positive myocytes than control hearts.
      Hence, these studies demonstrate that activated STAT-1 is a pro-apoptotic factor
      in cardiac myocytes exposed to I/R, and is therefore a potential therapeutic
      target for the prevention of cell death following I/R injury.

PMID- 12517720
TI  - Senescence: the cost of being young and healthy?

PMID- 12517721
TI  - The regulation of death-associated protein (DAP) kinase in apoptosis.
AB  - DAP-kinase is a calcium/calmodulin (Ca2+/CaM) serine/threonine kinase which
      positively mediates programmed cell death in a variety of cell systems. The
      kinase is localized to the actin microfilament and has a unique, multidomain
      structure consisting of ankyrin repeats and a death domain. One of the substrates
      of DAP-kinase was identified as myosin light chain (MLC), the phosphorylation of
      which mediates membrane blebbing. Another arm in its mode of action leads to the
      formation of autophagic vesicles. Recent work addressed its mode of regulation
      and identified a mechanism which restrains its apoptotic function in growing
      cells and enables its activation during cell death. It involves an inhibitory
      type of autophosphorylation on serine 308 within the CaM regulatory domain. This
      negative phosphorylation takes place in growing cells and is strongly reduced
      upon their exposure to the apoptotic stimulus of C6-ceramide. The substitution of
      serine 308 to alanine, which mimics the ceramide-induced dephosphorylation at
      this site, increases Ca2+/CaM-independent substrate phosphorylation, as well as
      binding and overall sensitivity of the kinase to CaM. At the cellular level, it
      strongly enhances the death-promoting activity of the kinase. These results are
      consistent with a molecular model in which phosphorylation on serine 308
      stabilizes a locked conformation of the CaM regulatory domain within the
      catalytic cleft and, simultaneously, also interferes with CaM binding. We propose
      that this unique mechanism of auto-inhibition evolved to impose a locking device
      which keeps DAP-kinase silent in healthy cells and ensures its activation only in
      response to apoptotic signals.

PMID- 12517722
TI  - Energetic depression caused by mitochondrial dysfunction.
AB  - Mitochondria not only provide most of the ATP needed for cell work and numerous
      specific anabolic and catabolic functions, they also contribute to Ca++
      signalling and play a key role in the pathway to cell death. Impairment of
      mitochondrial functions caused by mutations of the mt-genome or by acute
      processes, is responsible for numerous diseases. Decreased concentrations of
      adenine nucleotides, leaky outer and inner mitochondrial membranes, and decreased
      activities of respiratory chain enzymes contribute to depression of cellular
      energy metabolism, one of the most important consequences of mitochondrial
      impairment as characterized by decreased cytosolic phosphorylation potentials.

PMID- 12517723
TI  - Compromised interferon gamma (IFN-gamma) production in the elderly to both acute
      and latent viral antigen stimulation: contribution to the immune risk phenotype?
AB  - The elderly suffer from an increased incidence of infectious disease, accompanied
      by increased morbidity and mortality. Interferon-gamma plays an important role in
      defense against intracellular pathogens such as mycobacteria and viruses. A
      reduced capacity to produce this cytokine in the elderly, as demonstrated by our
      findings of significant decreases in IFN-gamma production in vitro on stimulation
      with bacterial products (LPS) or viral antigens (influenza vaccine), might
      therefore contribute to disease susceptibility. Moreover, accumulating data
      suggest that persistent infection with EBV and particularly CMV impacts upon the
      immune system in aging and may contribute to the immune risk phenotype (IRP),
      which predicts remaining longevity in the very elderly. Using tetramer technology
      and IFN-gamma ELISPOT assays, we found that the commonly-observed clonal
      expansions of CD8+ T-cells in the elderly were for the most part poorly
      functional CMV- and EBV-specific cells, expressing little CD28. The resulting
      accumulation of dysfunctional cells may lead to a reduction of the repertoire of
      functional T-cells available for responses to novel antigens. Further
      longitudinal studies are needed to demonstrate whether cytokines such as IFN-g
      are also part of the IRP. Improving the definition of the IRP will help to
      understand and thus prevent or reverse age-associated immune dysfunction.

PMID- 12517724
TI  - Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations.
AB  - Aging is associated with low-grade increases in circulating levels of TNF-alpha
      and IL-6. A wide range of factors, including smoking, obesity, infections, the
      decline in sex hormones, and the genotype, induce and modify this age-related
      inflammatory activity, which on the other hand may cause age-related pathology.
      Several classical risk factors are indeed controlled by TNF-alpha and IL-6. TNF
      alpha induces insulin resistance and endothelial dysfunction, IL-6 promotes
      procoagulant changes and both cytokines cause dyslipidaemia. Moreover, systemic
      low-grade elevations in both cytokines have been related to cardiovascular
      diseases and TNF-alpha has been associated with Alzheimer's disease and type 2
      diabetes mellitus. TNF-alpha and IL-6 are also differently and independently of
      each other associated with mortality in elderly populations, indicating points of
      distinction in the biological effects of the two cytokines. Moreover, the
      association between cytokines and mortality is independent of co-morbidity,
      suggesting that low-grade increases in circulating cytokines are strong,
      independent risk factors of morbidity and mortality in old populations, although
      life style factors and co-morbidity may modulate levels.

PMID- 12517725
TI  - Neisseria meningitidis can induce pro-inflammatory cytokine production via
      pathways independent from CD14 and toll-like receptor 4.
AB  - Fulminant meningococcal sepsis (FMS) is considered the prototypical Gram-negative
      sepsis. Lipopolysaccharide (LPS) is thought to be the main toxic element that
      induces pro-inflammatory cytokine production after interaction with CD14 and toll
      like receptor 4 (TLR4). However, there is increasing evidence that LPS is not the
      sole toxic element of meningococci. The aim of the present study was to determine
      the role of CD14 and TLR4 in pro-inflammatory cytokine induction by meningococci.
      To this end, cytokine induction by isolated meningoccal LPS, wild-type N.
      meningitidis H44/76 (LPS+-meningococci) matched for concentrations of LPS and LPS
      deficient N. meningitidis H44/76lpxA (LPS - -meningococci) was studied in human
      PBMCs and murine peritoneal macrophages (PMs). Pre-incubation of PBMCs with WT14,
      a monoclonal antibody against CD14, abolished TNF-alpha and IL-1beta induction by
      E. coli LPS, while cytokine induction by meningococcal LPS was only partially
      inhibited. When LPS+- and LPS - -meningococci at higher concentrations were used
      as stimuli, anti-CD14 had a minimal effect. In C3H/HeJ murine PMs, devoid of a
      functional TLR4, minimal IL-1alpha, IL-6 and TNF-alpha production was seen after
      stimulation with 10 ng/mL E. coli or meningococcal LPS. However, at higher
      concentrations (1000 ng LPS/mL) the production of TNF-alpha, but not IL-1alpha or
      IL-6, occurred also independently of TLR4. The expression of a functional TLR4 in
      murine PMs had no effect on the cytokine induction by LPS+- or LPS - 
      meningococci. It is concluded that pro-inflammatory cytokine induction by N.
      meningitidis can occur independently of CD14 and TLR4.

PMID- 12517726
TI  - Evaluation of tumor necrosis factor alpha production in ex vivo short term
      cultured whole blood from women with polycystic ovary syndrome.
AB  - In mammals, the pleiotropic biological functions of tumor necrosis factor alpha
      (TNF-alpha) may include important effects on human reproductive physiology. Thus,
      chronic anovulation, oligo or amenorrhea, infertility, hyperandrogenism, obesity,
      insulin resistance and increased TNFalpha serum levels have been observed in
      women affected by polycystic ovary syndrome (PCOS). Whole blood short - term cell
      cultures (WBSC) are simple systems where the capacity to produce TNF-alpha by
      circulating leukocytes, mainly of the macrophage/monocyte lineage, can be
      accurately quantified. Given the relevance of monocytes/macrophages in the
      production of TNF-alpha, in this study, in a control-case approach, WBSC from
      women with PCOS were analyzed in their basal and lipolysaccharide (LPS)-
      stimulated capacity to produce the cytokine. These measurements did not correlate
      with the increased serum levels of the cytokine and the normal levels of
      cortisol, found in PCOS women. Increased serum TNF-alpha levels in PCOS women
      correlated positively with body mass index and negatively with insulin
      sensitivity. In spite of the increased serum TNF-alpha levels in PCOS women,
      basal and LPS stimulated production of the cytokine, by the ex vivo WBSC from
      these patients, were within normal values.

PMID- 12517727
TI  - Plasma levels of interleukin-12 (IL-12), interleukin-18 (IL-18) and transforming
      growth factor beta (TGF-beta) in Plasmodium falciparum malaria.
AB  - The interaction between pro- and anti-inflammatory cytokines such as interleukin
      12 (IL-12), interleukin 18 (IL-18) and transforming growth factor beta (TGF-beta)
      may play an important role in malaria pathogenesis and outcome. IL-18 cooperates
      with IL-12 in the IFN-gamma production by T, B, and NK cells, and synergizes with
      IL-12 for IFN-gamma production by Th1 cells. Recently it has been demonstrated
      that these cytokines modulate the immunoresponse in Plasmodium falciparum
      malaria. The aim of this study was to measure the plasma levels of IL-12, IL-18
      and TGF-beta in 105 African children with various degrees of malaria, and
      correlate the production of these cytokines with the severity of the disease. IL
      12, IL-18 and TGF-beta levels were determined using enzyme-linked immunosorbent
      assay. The severity of malaria was established by parasitemia, clinical symptoms
      and haematological parameters. The levels of IL-12, IL-18 and TGF-beta were found
      to be significantly elevated (15.6 + / - 12.3, 22.7 + / - 13.8 pg/ml and 25.14 +
      / - 13.22 pg/ml respectively) in all of the children. IL-12 and IL-18 levels were
      significantly lower (13.2 + / - 5.53 and 21.5 + / - 10 pg/ml pg/ml) in children
      with severe disease, whereas the level of TGF-beta was higher (28.09 + / - 12.39
      pg/ml). In contrast, IL-12 and IL-18 levels were found to be higher (17.32 + / -
      7.8 pg/ml and 25.7 + / - 7.6 pg/ml) in patients with mild disease, whereas the
      level of TGF-beta was lower (20.92 + / - 12.76 pg/ml) compared to the severe
      malaria group. The correlation between IL-12 and IL-18 demonstrated a progressive
      relationship up to a value of IL-12 < 25 pg/ml, while IL-18 remained stable at
      higher levels of IL-12. An inverse correlation was found between IL-12 and TGF
      beta up to a value of IL-12 < 30, after which the level of TGF-beta remained
      stable. This finding suggests that fine mechanisms regulate the interaction
      between IL-12, IL-18 and TGF-beta in the immune response to Plasmodium
      falciparum.

PMID- 12517728
TI  - In vitro analysis of interferon gamma (IFN-gamma) and interleukin-12 (IL-12)
      production and their effects in ileal Crohn's disease.
AB  - Crohn's disease is an inflammatory disease of the gut in which tumour necrosis
      factor (TNF) and T helper 1 (Th1) cytokines (interleukin (IL)-12, interferon
      (IFN)-gamma) are thought to play a major role. After the successes obtained with
      neutralisation of TNF, interest is now growing for therapy aiming at
      neutralisation of Th1-associated cytokines. Since cytokines are linked in a
      delicate network, in vitro cultures of ileal lamina propria mononuclear cells
      (LPMC) were set up for evaluation of a) IFN-gamma and IL-12 production, b)
      effects of rhIFN-gamma and rhIL-12 and c) effects of anti-IFN-gamma and anti-IL
      12 on pro-inflammatory cytokines and IL-10 production. LPMC were isolated from
      surgical specimens of a total of 27 Crohn's disease and 17 caecum carcinoma
      (control) patients. Cells were stimulated with CD40L (which triggers myeloid CD40
      expressing cells) or anti-CD3 +CD80 (which triggers T cells). LPMC from involved
      ileal, Crohn's disease produced, in both non-stimulated and stimulated
      conditions, more IFN-gamma and IL-12p70 than LPMC from non-involved tissue or
      from control patients. rhIFN-gamma significantly enhanced TNF production in both
      controls and in ileal Crohn's disease patients, while rhIL-12 enhanced IFN-gamma
      but not TNF production. LPMC from involved tissue were more sensitive to IL-12
      than control LPMC. LP-T cell-dependent activation of monocytes was then studied
      by co-culture of anti-CD3/CD80-stimulated LPMC with fresh monocytes, which
      resulted in high IL-12, IFN-gamma, TNF and IL-10 production. The data show that
      neutralisation of either IL-12 or IFN-gamma with mAb in these cultures also
      affects secretion of the reciprocal cytokine and (in the case of anti-IL-12) also
      that of the anti-inflammatory cytokine IL-10. However, no effect of anti-IL-12 or
      anti-IFN-gamma on production of TNF, a cytokine with an important pathogenic role
      in Crohn's disease, could be found. Therapies aiming at neutralisation of IFN
      gamma or IL-12 are therefore unlikely to replace anti-TNF, but they might provide
      an additive or synergistic effect.

PMID- 12517729
TI  - Differential modulation of interleukin-2-and interleukin-4-mediated early
      activation of normal human B lymphocytes by the caspase inhibitor zVAD-fmk.
AB  - Caspases are a group of cysteine-related proteases that control the process of
      apoptosis and may also be involved in the control of lymphocyte activation. We
      show here that the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val
      Ala-Asp (Ome)-fluoromethylketone (zVAD-fmk) prevents the proliferation of resting
      human B tonsilar lymphocytes mediated by the B cell mitogen SAC or the
      combination of anti-mu Ab and IL-2. zVAD-fmk inhibits IL-2-induced
      phosphorylation of the retinoblastoma protein, and cyclin D2 expression. However,
      neither the IL-2-mediated proliferation of cycling activated B cells nor that of
      lymphoma cells were inhibited by zVAD-fmk, suggesting that only the early steps
      of SAC- or IL-2-mediated B cell activation were sensitive to the inhibitory
      properties of zVAD-fmk. Our data also demonstrated that the inhibitory effect of
      zVAD-fmk was not observed when B cells were activated with IL-4 in the presence
      of either anti-mu Ab or anti-CD40 Ab. Thus, our results suggest that caspase
      activation is required for the IL-2-mediated entry of primary B lymphocytes into
      the cell cycle and show that caspase activation plays different roles in IL-2-
      and IL-4-mediated B cell proliferation.

PMID- 12517730
TI  - Prolactin-cytokine network in the defence against Acanthamoeba castellanii in
      murine microglia [corrected].
AB  - In the central nervous system, cytokine-primed microglia play a pivotal role in
      host defence against parasite infections. In this study, the effect of
      recombinant (r) prolactin (rPRL) and rIFN-gamma on A. castellanii infection in
      murine microglia was examined. Priming of microglia with rPRL and rIFN-gamma
      synergistically triggered, in a dose-dependent manner, amebastatic activity and
      the release of endogenous IL-1alpha, IL-1beta, IL-6 and TNF-alpha. More than 53,
      57, 49, 89 or 96 % of amebastatic activity was abrogated by anti-PRLR, IFN
      gammaR, IL-1beta (but not IL-1alpha), IL-6 or TNF-alpha antibodies, suggesting
      that these two receptors and proinflammatory cytokines participate in the anti
      microbial function. Inasmuch as DPI and AET, both inhibitors of NO synthase,
      blocked amebastatic activity only during the priming process, the NO-dependent
      pathway itself appears not to be directly involved in the anti-parasitic
      capacity. These data suggest that the PRL/PRLR and IFN-gamma/IFN-gamma/R
      complexes, by the induction of the IFN-gammaR on microglia, up-regulate the
      release of endogenous TNF-alpha, IL-6 and IL-1beta by these cells, which could
      trigger anti-microbial activity against A. castellanii infection in the brain
      [corrected].

PMID- 12517731
TI  - Cytokine-induced neutrophil chemoattractant 1 (CINC-1) mediates the sympathetic
      component of inflammatory mechanical hypersensitivitiy in rats.
AB  - The hyperalgesic effect of cytokine-induced neutrophil chemoattractant 1 (CINC
      1/CXCL1) was measured in a model of mechanical hyperalgesia in rats. CINC-1
      evoked a dose-dependent mechanical hypersensitivity, which was already
      significant 2 h after the cytokine injection, peaked 4 h after and decreased
      thereafter. The local pre-treatment of the rats with the beta-adrenoceptor
      antagonist, atenolol (25 microg paw-1), but not with the cyclooxygenase inhibitor
      indomethacin (100 microg paw-1), inhibited (86%) the CINC-1-induced
      hypersensitivity. Conversely, IL-1beta-evoked hypersensitivity was inhibited
      (76%) by local pre-treatment of the animals with indomethacin, but not by
      atenolol. Carrageenin- and TNF-alpha-evoked hypersensitivity were attenuated to
      about the same extent (50%) by antisera neutralising CINC-1 or IL-1beta. The
      association of both antisera abolished the hypersensitivity effect of carrageenin
      and TNF-alpha. In addition, carrageenin, LPS and TNF-alpha were shown to
      stimulate the production of immunoreactive CINC-1 in the skin of injected paws.
      These data suggest that CINC-1, released at sites of inflammation, mediates
      inflammatory hyperalgesia in rats via release of sympathomimetic amines.

PMID- 12517732
TI  - A CXC chemokine sequence isolated from the rainbow trout Oncorhynchus mykiss
      resembles the closely related interferon-gamma-inducible chemokines CXCL9, CXCL10
      and CXCL11.
AB  - A sequence encoding a CXC - type chemokine from rainbow trout was found to most
      resemble members of the CXCL9/CXCL10/CXCL11 sub-family. In mammals, all 3
      chemokines are regulated by IFN-gamma and are chemotactic for activated T
      lymphocytes. The trout chemokine (gammaIP1), with a message of 787 nucleotides,
      contains 100 amino acids in a typical non-ELR CXC chemokine arrangement. A second
      sequence (gammaIP2), with 6 nucleotide differences in the coding region when
      compared to the first, was also identified although it is not known whether this
      is a second functional gene or a second allele. The gene is separated onto 4
      exons, and the introns intervene in conserved positions according to the
      mammalian equivalents. The sequence encoded by the second exon shares the highest
      amino acid identity (37%) with CXCL10, with lower values of identity to other CXC
      chemokines (17-31%). Furthermore, phylogenetic analysis groups the trout
      chemokine with mammalian CXCL9, CXCL10 and CXCL11 peptides. Constitutive
      expression of gammaIP is seen in trout gill and low level expression in spleen,
      head kidney and liver. In RTS-11 cells, gammaIP expression can be induced with
      poly I:C, but not by LPS, suggesting virus-mediated regulation of gammaIP.
      Intraperitoneal injection of recombinant trout TNF-alpha caused elevation in
      gammaIP mRNA levels in trout head kidney.

PMID- 12517733
TI  - French Society of Immunology: Cytokine Meeting May 16-17, 2002, Le Croisic, Port
      aux-Rocs, France.

PMID- 12517734
TI  - Downregulation of renal aquaporins in response to unilateral ureteral
      obstruction.
AB  - The expression of aquaporin-2 (AQP2) is decreased in rats with bilateral ureteral
      obstruction (BUO) and unilateral ureteral obstruction (UUO). Therefore, the
      expression of additional renal aquaporins (AQP1-4) and phosphorylated AQP2 (p
      AQP2), known to play a role in urinary concentration, was examined in a Wistar
      rat model with 24 h of UUO. In obstructed kidneys, immunoblotting revealed a
      significant decrease in the expression of inner medullary AQP2 to 42 +/- 4, p
      AQP2 to 23 +/- 5, AQP3 to 19 +/- 6, AQP4 to 11 +/- 5, and AQP1 to 64 +/- 8% of
      sham levels. AQP1 expression located in the proximal tubule decreased to 74 +/-
      4% of sham levels (P < 0.05). Immunocytochemistry confirmed the downregulation of
      AQP3, AQP4, and p-AQP2. In contralateral nonobstructed kidneys, immunoblotting
      also revealed significant reductions of AQP1 in the inner medulla, outer medulla,
      and cortex, whereas expression of AQP2, AQP3, AQP4, and p-AQP2 was unchanged.
      Furthermore, we collected the urine from both obstructed and nonobstructed
      kidneys for 2 h, respectively, after 24 h of UUO. Urine collection from
      obstructed kidneys during 2 h after release of UUO revealed a significant
      reduction in urine osmolality and solute-free water reabsorption (T(c)H(2)O).
      Moreover, an increase in urine production and T(c)H(2)O was observed in
      contralateral kidneys. To examine whether vasopressin-independent mechanisms are
      involved in AQP2 regulation, vasopressin-deficient Brattleboro (BB) rats with 24
      h of UUO were examined. Immunoblotting revealed downregulation of AQP2, p-AQP2,
      AQP3, and AQP1 in obstructed kidneys and downregulation of p-AQP2 and AQP1 in
      nonobstructed kidneys. In conclusion, 1) UUO is associated with severe
      downregulation of AQP2, AQP3, AQP4, and AQP1; thus all of these AQPs may play
      important roles in the impaired urinary concentrating capacity in the obstructed
      kidney; 2) the reduced levels of AQP1 in the nonobstructed kidney may contribute
      to the compensatory increase in urine production; and 3) downregulation of AQPs
      in BB rats supports the view that vasopressin-independent pathways may be
      involved in AQP2 and AQP3 regulation in the obstructed kidney.

PMID- 12517735
TI  - Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal
      tubular cells.
AB  - Persistent proteinuria has been indicated to be a major risk factor for the
      development of tubulointerstitial damage through a process of proinflammatory
      molecule expression. Monocyte chemoattractant protein-1 (MCP-1) was shown to
      contribute to recruitment of immune cells into the renal interstitium in acute
      and chronic renal diseases. However, the molecular mechanisms by which
      proteinuria causes MCP-1 expression in proximal tubular cells have not been fully
      clarified. In this study, we examined whether albumin overload-induced MCP-1
      expression was regulated by mitogen-activated protein kinase (MAPK) in mouse
      proximal tubular (mProx) cells. Exposure of mProx cells to delipidated bovine
      serum albumin (BSA) induced mRNA and protein expression of MCP-1 in a time- and
      dose-dependent manner. BSA activated extracellular signal-regulated kinase
      (ERK1/2) and p38 MAPK. The MEK inhibitor U-0126 partially suppressed BSA-induced
      MCP-1 expression and MCP-1 promoter/luciferase reporter activity. U-0126 also
      inhibited an increase in nuclear factor-kappaB and activator protein-1 DNA
      binding activity of MCP-1 promoter by protein overload in mProx cells. In
      addition, we found that U-0126 inhibited BSA-induced nuclear factor-kappaB
      reporter activity and inhibitory protein degradation in mProx cells. In
      conclusion, these findings indicate that ERK signaling is involved in BSA-induced
      MCP-1 expression in mProx cells.

PMID- 12517736
TI  - Thromboxane synthase and TP receptor mRNA in rat kidney and brain: effects of
      salt intake and ANG II.
AB  - A TP receptor (TP-R) mimetic causes salt-sensitive hypertension and renal
      afferent arteriolar vasoconstriction. TP-Rs mediate effects of ANG II on renal
      vascular resistance and drinking. Therefore, we investigated the hypothesis that
      thromboxane A(2) synthase (TxA(2)-S) and/or TP-R expression is regulated by salt
      and/or ANG II. Rats (n = 6) received high-salt (HS) or low-salt (LS) diets.
      Additional HS-diet rats received ANG II while other HS- and LS-diet rats received
      the AT(1) receptor (AT(1)-R) antagonist losartan. Excretion of thromboxane B(2)
      by conscious rats was increased with the HS diet compared with the LS diet (126
      +/- 10 vs. 48 +/- 5 pmol/24 h, respectively; P < 0.01). The mRNA abundance for TP
      Rs (relative to beta-actin) in the kidney cortex was enhanced 30% by the HS diet
      (P < 0.001) and was reduced 50% by the addition of ANG II (P < 0.001). However,
      during losartan administration, the effects of salt were reversed; mRNA more than
      doubled during the LS diet (P < 0.001). Similarly, the mRNA abundance for TP-Rs
      in the brain stem was reduced by 50% with the addition of ANG II (P < 0.001) and
      during losartan administration was almost doubled by the LS diet (P < 0.001). The
      mRNA abundance for TxA(2)-S in the kidney cortex also was increased many times
      with the HS diet (P < 0.001). In contrast, the mRNA for TxA(2)-S in the brain was
      unaffected by salt. ANG II did not affect TxA(2)-S at either site. During
      losartan administration, TxA(2)-S increased modestly in the brain stem with the
      LS diet. mRNA abundance for TP-Rs in the kidney cortex and brain stem is
      suppressed by ANG II acting on AT(1)-Rs. In the absence of AT(1)-Rs, expression
      of TP-Rs at both sites is enhanced by LS intake. In contrast, ANG II does not
      affect the mRNA abundance for TxA(2)-S. Expression of TxA(2)-S is enhanced by HS
      intake in the kidney cortex but by LS intake in the brain stem only during
      losartan administration. Thus TP-Rs are strongly dependent on ANG II acting on
      AT(1)-Rs, whereas TxA(2)-S is regulated differentially in the kidney cortex and
      brain stem by salt intake.

PMID- 12517739
TI  - On-line analysis of gap junctions reveals more efficient electrical than dye
      coupling between islet cells.
AB  - Pancreatic beta-cells constitute a well-communicating multicellular network that
      permits a coordinated and synchronized signal transmission within the islet of
      Langerhans that is necessary for proper insulin release. Gap junctions are the
      molecular keys that mediate functional cellular connections, which are
      responsible for electrical and metabolic coupling in the majority of cell types.
      Although the role of gap junctions in beta-cell electrical coupling is well
      documented, metabolic communication is still a matter of discussion. Here, we
      have addressed this issue by use of a fluorescence recovery after photobleaching
      (FRAP) approach. This technique has been validated as a reliable and noninvasive
      approach to monitor functional gap junctions in real time. We show that control
      pancreatic islet cells did not exchange a gap junction-permeant molecule in
      either clustered cells or intact islets of Langerhans under conditions that
      allowed cell-to-cell exchange of current-carrying ions. Conversely, we have
      detected that the same probe was extensively transferred between islet cells of
      transgenic mice expressing connexin 32 (Cx32) that have enhanced junctional
      coupling properties. The results indicate that the electrical coupling of native
      islet cells is more extensive than dye communication. Dye-coupling domains in
      islet cells appear more restricted than previously inferred with other methods.

PMID- 12517738
TI  - Modulation of muscle insulin resistance by selective inhibition of GSK-3 in
      Zucker diabetic fatty rats.
AB  - A role for elevated glycogen synthase kinase-3 (GSK-3) activity in the
      multifactorial etiology of insulin resistance is now emerging. However, the
      utility of specific GSK-3 inhibition in modulating insulin resistance of skeletal
      muscle glucose transport is not yet fully understood. Therefore, we assessed the
      effects of novel, selective organic inhibitors of GSK-3 (CT-98014 and CT-98023)
      on glucose transport in insulin-resistant muscles of Zucker diabetic fatty (ZDF)
      rats. Incubation of type IIb epitrochlearis and type I soleus muscles from ZDF
      rats with CT-98014 increased glycogen synthase activity (49 and 50%,
      respectively, P < 0.05) but did not alter basal glucose transport (2-deoxyglucose
      uptake). In contrast, CT-98014 significantly increased the stimulatory effects of
      both submaximal and maximal insulin concentrations in epitrochlearis (37 and 24%)
      and soleus (43 and 26%), and these effects were associated with increased cell
      surface GLUT4 protein. Lithium enhanced glycogen synthase activity and both basal
      and insulin-stimulated glucose transport in muscles from ZDF rats. Acute oral
      administration (2 x 30 mg/kg) of CT-98023 to ZDF rats caused elevations in GSK-3
      inhibitor concentrations in plasma and muscle. The glucose and insulin responses
      during a subsequent oral glucose tolerance test were reduced by 26 and 34%,
      respectively, in the GSK-3 inhibitor-treated animals. Thirty minutes after the
      final GSK-3 inhibitor treatment, insulin-stimulated glucose transport was
      significantly enhanced in epitrochlearis (57%) and soleus (43%). Two hours after
      the final treatment, insulin-mediated glucose transport was still significantly
      elevated (26%) only in the soleus. These results indicate that specific
      inhibition of GSK-3 enhances insulin action on glucose transport in skeletal
      muscle of the insulin-resistant ZDF rat. This unique approach may hold promise as
      a pharmacological treatment against insulin resistance of skeletal muscle glucose
      disposal.

PMID- 12517740
TI  - Inhibition of IFN-gamma -induced STAT1 activation by 15- deoxy-Delta 12,14
      prostaglandin J2.
AB  - The inhibitory actions of 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)) on
      inflammatory gene expression have been attributed to the ability of this
      prostaglandin to inhibit the activation of NF-kappaB. In this study, we have
      identified an additional signaling pathway sensitive to inhibition by PGJ(2). We
      show that PGJ(2) inhibits interferon (IFN)-gamma-stimulated phosphorylation and
      DNA-binding activity of STAT1. The inhibitory actions on STAT1 phosphorylation
      are first apparent after a 1- to 2-h incubation and are maximal after a 6-h
      incubation with PGJ(2), and they correlate with the expression of heat shock
      protein (HSP)70 in islets. In previous studies, we have correlated the inhibitory
      actions of PGJ(2) on inducible nitric oxide synthase (iNOS) expression and NF
      kappaB activation in response to IL-1 with the increased expression of HSP70.
      Using overexpression and antisense depletion, we provide evidence that HSP70 does
      not mediate the inhibitory actions of PGJ(2) on IL-1-induced NF-kappaB or IFN
      gamma-induced STAT1 activation or cytokine-stimulated iNOS expression by beta
      cells. Last, we show that the inhibitory actions of a short 6-h pulse with PGJ(2)
      on IL-1 plus IFN-gamma-stimulated iNOS expression and NO production by beta-cells
      are persistent for extended periods (< or =48 h). These findings suggest that
      PGJ(2) inhibits multiple cytokine-signaling pathways (IL-1 and IFN-gamma), that
      the inhibitory actions are persistent for extended periods, and that increased
      HSP70 expression correlates with, but does not appear to mediate, the inhibitory
      actions of PGJ(2) on IL-1 and IFN-gamma signaling in beta-cells.

PMID- 12517741
TI  - Development of models to predict anabolic response to testosterone administration
      in healthy young men.
AB  - Considerable heterogeneity exists in the anabolic response to androgen
      administration; however, the factors that contribute to variation in an
      individual's anabolic response to androgens remain unknown. We investigated
      whether testosterone dose and/or any combination of baseline variables, including
      concentrations of hormones, age, body composition, muscle function, and
      morphometry or polymorphisms in androgen receptor could explain the variability
      in anabolic response to testosterone. Fifty-four young men were treated with a
      long-acting gonadotropin-releasing hormone (GnRH) agonist and one of five doses
      (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE) for 20 wk.
      Anabolic response was defined as a change in whole body fat-free mass (FFM) by
      dual-energy X-ray absorptiometry (DEXA), appendicular FFM (by DEXA), and thigh
      muscle volume (by magnetic resonance imaging) during TE treatment. We used
      univariate and multivariate analysis to identify the subset of baseline measures
      that best explained the variability in anabolic response to testosterone
      supplementation. The three-variable model of TE dose, age, and baseline prostate
      specific antigen (PSA) level explained 67% of the variance in change in whole
      body FFM. Change in appendicular FFM was best explained (64% of the variance) by
      the linear combination of TE dose, baseline PSA, and leg press strength, whereas
      TE dose, log of the ratio of luteinizing hormone to testosterone concentration,
      and age explained 66% of the variation in change in thigh muscle volume. The
      models were further validated by using Ridge analysis and cross-validation in
      data subsets. Only the model using testosterone dose, age, and PSA was a
      consistent predictor of change in FFM in subset analyses. The length of CAG tract
      was only a weak predictor of change in thigh muscle volume and lean body mass.
      Hence, the anabolic response of healthy, young men to exogenous testosterone
      administration can largely be predicted by the testosterone dose.

PMID- 12517744
TI  - Akt activation promotes degradation of tuberin and FOXO3a via the proteasome.
AB  - Growth factor receptors promote cell growth and survival by stimulating the
      activities of phosphatidylinositol 3-kinase and Akt/PKB. Here we report that Akt
      activation causes proteasomal degradation of substrates that control cell growth
      and survival. Expression of activated Akt triggered proteasome-dependent declines
      in the protein levels of the Akt substrates tuberin, FOXO1, and FOXO3a. The
      addition of proteasome inhibitors stabilized the phosphorylated forms of multiple
      Akt substrates, including tuberin and FOXO proteins. Activation of Akt triggered
      the ubiquitination of several proteins containing phosphorylated Akt substrate
      motifs. Together the data indicate that activated Akt stimulates proteasomal
      degradation of its substrates and suggest that Akt-dependent cell growth and
      survival are induced through the degradation of negative regulators of these
      processes.

PMID- 12517745
TI  - The glycoprotein Ib-IX-V complex mediates localization of factor XI to lipid
      rafts on the platelet membrane.
AB  - Factor XI binds to activated platelets where it is efficiently activated by
      thrombin. The factor XI receptor is the platelet membrane glycoprotein (GP) Ib-IX
      V complex (Baglia, F. A., Badellino, K. O., Li, C. Q., Lopez, J. A., and Walsh,
      P. N. (2002) J. Biol. Chem. 277, 1662-1668), a significant fraction of which
      exists within lipid rafts on stimulated platelets (Shrimpton, C. N., Borthakur,
      G., Larrucea, S., Cruz, M. A., Dong, J. F., and Lopez, J. A. (2002) J. Exp. Med.
      196, 1057-1066). Lipid rafts are membrane microdomains enriched in cholesterol
      and sphingolipids implicated in localizing membrane ligands and in cellular
      signaling. We now show that factor XI was localized to lipid rafts in activated
      platelets ( approximately 8% of total bound) but not in resting platelets.
      Optimal binding of factor XI to membrane rafts required prothrombin (and Ca2+) or
      high molecular weight kininogen (and Zn2+), which are required for factor XI
      binding to platelets. An antibody to GPIb (SZ-2) that disrupts factor XI binding
      to the GPIb-IX-V complex also disrupted factor XI-raft association. The isolated
      recombinant Apple 3 domain of factor XI, which mediates factor XI binding to
      platelets, also completely displaces factor XI from membrane rafts. To
      investigate the physiological relevance of the factor XI-raft association, the
      structural integrity of lipid rafts was disrupted by cholesterol depletion
      utilizing methyl-beta-cyclodextrin. Cholesterol depletion completely prevented
      FXI binding to lipid rafts, and initial rates of factor XI activation by thrombin
      on activated platelets were inhibited >85%. We conclude that factor XI is
      localized to GPIb in membrane rafts and that this association is important for
      promoting the activation of factor XI by thrombin on the platelet surface.

PMID- 12517753
TI  - Structure, activity, and distribution of fish osteocalcin.
AB  - Osteocalcin (bone Gla protein) is an extracellular matrix protein synthesized by
      osteoblasts that is a marker of bone. Osteocalcin probably originated in the
      ancestors of Teleostei or bony fish and of the Tetrapoda or amphibians, reptiles,
      birds, and mammals. We have characterized the Cyprinus carpio (carp) osteocalcin
      for mineral binding to hydroxyapatite, amino acid sequence, and extent of
      secondary structure. Hydroxyapatite binding is enhanced in the presence of
      calcium. The alpha-helical content of teleost osteocalcin increases and beta
      sheet structure decreases upon calcium binding, similar to findings in calf
      osteocalcin. The gene structure and primary sequence of prepro-osteocalcin from 2
      pufferfish compared with carp shows that there are many conserved features in
      teleost osteocalcin genes. Using an immunoassay for carp osteocalcin, we
      determined that the relative content of osteocalcin is highest in dorsal fin
      spines and other bones and lowest in scales. The carp osteocalcin antibodies,
      cross-reactive to other species of fish, were used to study the role of
      osteocalcin in teleost model systems.

PMID- 12517756
TI  - The low sulfated chondroitin sulfate proteoglycans of human placenta have sulfate
      group-clustered domains that can efficiently bind Plasmodium falciparum-infected
      erythrocytes.
AB  - Plasmodium falciparum infection in pregnant women results in the chondroitin 4
      sulfate-mediated adherence of the parasite-infected red blood cells (IRBCs) in
      the placenta, adversely affecting the health of the fetus and mother. We have
      previously shown that unusually low sulfated chondroitin sulfate proteoglycans
      (CSPGs) in the intervillous spaces of the placenta are the receptors for IRBC
      adhesion, which involves a chondroitin 4-sulfate motif consisting of six
      disaccharide moieties with approximately 30% 4-sulfated residues. However, it was
      puzzling how the placental CSPGs, which have only approximately 8% of the
      disaccharide 4-sulfated, could efficiently bind IRBCs. Thus, we undertook to
      determine the precise structural features of the CS chains of placental CSPGs
      that interact with IRBCs. We show that the placental CSPGs are a mixture of two
      major populations, which are similar by all criteria except differing in their
      sulfate contents; 2-3% and 9-14% of the disaccharide units of the CS chains are 4
      sulfated, and the remainder are nonsulfated. The majority of the sulfate groups
      in the CSPGs are clustered in CS chain domains consisting of 6-14 repeating
      disaccharide units. While the sulfate-rich regions of the CS chains contain 20
      28% 4-sulfated disaccharides, the other regions have little or no sulfate.
      Further, we find that the placental CSPGs are able to efficiently bind IRBCs due
      to the presence of 4-sulfated disaccharide clusters. The oligosaccharides
      corresponding to the sulfate-rich domains of the CS chains efficiently inhibited
      IRBC adhesion. Thus, our data demonstrate, for the first time, the unique
      distribution of sulfate groups in the CS chains of placental CSPGs and that these
      sulfate-clustered domains have the necessary structural elements for the
      efficient adhesion of IRBCs, although the CS chains have an overall low degree of
      sulfation.

PMID- 12517755
TI  - The selectivity and inhibition of AlkB.
AB  - AlkB is one of four proteins involved in the adaptive response to DNA alkylation
      damage in Escherichia coli and is highly conserved from bacteria to humans.
      Recent analyses have verified the prediction that AlkB is a member of the Fe(II)
      and 2-oxoglutarate (2OG)-dependent oxygenase family of enzymes. AlkB mediates
      repair of methylated DNA by direct demethylation of 1-methyladenine and 3
      methylcytosine lesions. Other members of the Fe(II) and 2OG-dependent oxygenase
      family, including those involved in the hypoxic response, are targets for
      therapeutic intervention. Assays measuring 2OG turnover were used to investigate
      the selectivity of AlkB. 1-Methyladenosine, 1-methyl-2'-deoxyadenosine, 3
      methylcytidine, and 3-methyl-2'-deoxycytidine all stimulated 2OG turnover by AlkB
      but were not demethylated indicating an uncoupling of 2OG and prime substrate
      oxidation and that oligomeric DNA is required for hydroxylation and subsequent
      demethylation. In contrast the equivalent unmethylated nucleosides did not
      stimulate 2OG turnover indicating that the presence of a methyl group in the
      substrate is important in initiating oxidation of 2OG. Stimulation of 2OG
      turnover by 1-methyladenosine was highly dependent on the presence of a reducing
      agent, ascorbate or dithiothreitol. Following the observation that AlkB is
      inhibited by high concentrations of 2OG, analogues of 2OG, including 2
      mercaptoglutarate, were found to specifically inhibit AlkB. The flavonoid
      quercetin inhibits both AlkB and the 2OG oxygenase factor-inhibiting hypoxia
      inducible factor (FIH) in vitro. FIH inhibition by quercetin occurs in the
      presence of excess iron indicating a specific interaction, while the inhibition
      of AlkB by quercetin is, predominantly, due to nonspecific iron chelation.

PMID- 12517763
TI  - The EphB6 receptor inhibits JNK activation in T lymphocytes and modulates T cell
      receptor-mediated responses.
AB  - EphB6 is the most recently identified member of the Eph receptor tyrosine kinase
      family. EphB6 is primarily expressed in thymocytes and a subpopulation of T
      cells, suggesting that it may be involved in regulation of T lymphocyte
      differentiation and functions. We show here that overexpression of EphB6 in
      Jurkat T cells and stimulation with the EphB6 ligand, ephrin-B1, results in the
      selective inhibition of TCR-mediated activation of JNK but not the MAPK pathway.
      EphB6 appears to suppress the JNK pathway by preventing T cell receptor (TCR)
      induced activation of the small GTPase Rac1, a critical event in initiating the
      JNK cascade. Furthermore, EphB6 blocked anti-CD3-induced secretion of IL-2 and
      CD25 expression in a ligand-dependent manner. Dominant negative EphB6 suppressed
      the inhibitory activity of the endogenous receptor and enhanced anti-CD3-induced
      JNK activation, CD25 expression, and IL-2 secretion, confirming the requirement
      for EphB6-specific signaling. Activation of the JNK pathway and the establishment
      of an IL-2/IL-2R autocrine loop have been shown to play a role in the negative
      selection of CD4(+)CD8(+) self-reacting thymocytes. In agreement, stimulation of
      murine thymocytes with ephrin-B1 not only blocked anti-CD3-induced CD25 up
      regulation and IL-2 production, but also inhibited TCR-mediated apoptosis. Thus,
      EphB6 may play an important role in regulating thymocyte differentiation and
      modulating responses of mature T cells.

PMID- 12517764
TI  - The MPB83 antigen from Mycobacterium bovis contains O-linked mannose and (1-->3)
      mannobiose moieties.
AB  - Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of human
      and bovine tuberculosis, have been reported to express a range of surface and
      secreted glycoproteins, although only one of these has been subjected to detailed
      structural analysis. We describe the use of a genetic system, in conjunction with
      lectin binding, to characterize the points of attachment of carbohydrate moieties
      to the polypeptide backbone of a second mycobacterial glycoprotein, antigen MPB83
      from M. bovis. Biochemical and structural analysis of the native MPB83 protein
      and derived peptides demonstrated the presence of 3 mannose units attached to two
      threonine residues. Mannose residues were joined by a (1 --> 3) linkage, in
      contrast to the (1 --> 2) linkage previously observed in antigen MPT32 from M.
      tuberculosis and the (1 --> 2) and (1 --> 6) linkages in other mycobacterial
      glycolipids and polysaccharides. The identification of glycosylated antigens
      within the M. tuberculosis complex raises the possibility that the carbohydrate
      moiety of these glycoproteins might be involved in pathogenesis, either by
      interaction with mannose receptors on host cells, or as targets or modulators of
      the cell-mediated immune response. Given such a possibility characterization of
      mycobacterial glycoproteins is a step toward understanding their functional role
      and elucidating the mechanisms of mycobacterial glycosylation.

PMID- 12517767
TI  - Targeting the epidermal growth factor receptor in cancer: apoptosis takes center
      stage.
AB  - Aberrant activation of the epidermal growth factor receptor (EGFR) is frequently
      observed in neoplasia,notably in tumors of epithelial origin. Attempts to treat
      such tumors with EGFR antagonists have met with remarkable initial successes,
      particularly when EGFR antagonists were used in combination with chemotherapy or
      ionizing radiation. Considering the almost ubiquitous expression of the EGFR in
      normal epithelial tissues, these clinical trials also revealed a surprisingly low
      rate of adverse side effects associated with EGFR blockade. This review
      highlights antiapoptotic effects of EGFR activation as they relate to therapeutic
      efficacy of EGFR blockade. We introduce the concept that control of cell survival
      through EGFR activation is conditional in the sense that it is rate limiting to
      tumor cell survival but not to survival of normal epithelial cells. Specifically,
      normal epithelial cells are provided with a full complement of physiological cell
      cell contacts and cell-matrix interactions that lessen their dependence on
      survival signals provided by the EGFR. By contrast, malignant tumor cells faced
      with inadequate cell-matrix contacts critically depend on EGFR activation for
      survival, rendering them more susceptible to apoptosis induction by EGFR
      blockade. Redundant control of cell survival by the EGFR and extracellular
      matrix/cell adhesion receptors is enabled, in part, by shared signal transduction
      pathways that control expression and activation states of members of the Bcl-2
      family of apoptosis regulators.

PMID- 12517768
TI  - Microarray analysis reveals distinct gene expression profiles among different
      histologic types of endometrial cancer.
AB  - Previous studies of oncogene and tumor suppressor gene alterations have suggested
      that differences exist in the molecular pathogenesis of the various histological
      types of endometrial cancer. To elucidate further the molecular events involved
      in endometrial carcinogenesis, we examined global expression patterns of 16
      nonendometrioid cancers (13 serous papillary and 3 clear cell), 19 endometrioid
      cancers, and 7 age-matched normal endometria using cDNA microarrays. Unsupervised
      analysis of gene expression identified 191 genes that exhibited >2-fold
      differences (P < 0.001) between the histological groups. Many genes were
      similarly dysregulated in both nonendometrioid and endometrioid cancers relative
      to normal endometria. Gene expression differences in only 24 transcripts could
      distinguish serous from endometrioid cancers, the two most common subgroups.
      These data provide the basis for investigation of previously unrecognized novel
      pathways involved in the development of endometrial cancers.

PMID- 12517769
TI  - Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma
      patients is determined by their maturation state.
AB  - Dendritic cells are the professional antigen-presenting cells of the immune
      system. To induce an effective immune response, these cells should not only
      express high levels of MHC and costimulatory molecules but also migrate into the
      lymph nodes to interact with naive T cells. Here, we demonstrate that in vitro
      generated mature, but not immature dendritic cells, efficiently migrate into the
      T-cell areas of lymph nodes of melanoma patients. This difference is confirmed by
      in vitro studies, in which immature dendritic cells are strongly adherent,
      whereas mature dendritic cells remain highly motile. Our present findings
      demonstrate that the ability of dendritic cells to mount a proper immune response
      correlates with their ability to migrate both in vitro and in vivo.

PMID- 12517770
TI  - Nuclear factor-kappaB p65 mediates tumor necrosis factor alpha-induced nuclear
      translocation of telomerase reverse transcriptase protein.
AB  - Sustained proliferation of cancer cells requires telomerase to maintain telomeres
      that regulate chromosomal stability and cellular mitosis. Expression of human
      telomerase reverse transcriptase (hTERT) catalytic subunit, which modulates
      telomerase activity, is regulated at both the transcriptional level and via
      phosphorylation by Akt kinase. Moreover, nuclear localization of hTERT is
      required to promote elongation of telomere sequences. In this study, we show for
      the first time that hTERT protein interacts directly with nuclear factor (NF)
      kappaB p65 in MM.1S cells. Importantly, tumor necrosis factor alpha (TNFalpha)
      modulates telomerase activity by inducing translocation from the cytoplasm to the
      nucleus of hTERT protein bound to NF-kappaB p65. Conversely, a specific IkappaB
      kinase (IKK) inhibitor PS-1145, and a specific NF-kappaB nuclear translocation
      inhibitor SN-50, both block TNFalpha-induced hTERT nuclear translocation. These
      studies suggest that NF-kappaB p65 plays a pivotal role in regulating telomerase
      by modulating its nuclear translocation.

PMID- 12517771
TI  - Requirement for XRCC4 and DNA ligase IV in alignment-based gap filling for
      nonhomologous DNA end joining in vitro.
AB  - In the nonhomologous end joining pathway of DNA double-strand break repair, the
      ligation step is catalyzed by a complex of XRCC4 and DNA ligase IV. Extracts of
      CHO-K1 cells are able to accurately rejoin a site-specific free radical-mediated
      double-strand break with partially complementary overhangs, by a mechanism
      involving alignment-based gap filling followed by ligation. Extracts of XR-1
      cells, which lack XRCC4 and DNA ligase IV, carried out neither gap filling nor
      ligation. Supplementation of the extracts with recombinant XRCC4/ligase IV, but
      not with XRCC4 alone, restored gap filling and accurate end joining. The results
      imply that XRCC4 and ligase IV are essential for alignment-based gap filling, as
      well as for final ligation of the breaks.

PMID- 12517772
TI  - Nuclear factor-kappaB protects the liver against genotoxic stress and functions
      independently of p53.
AB  - p53 and NF-kappaB are two key effectors in the chemotherapy-induced genotoxic
      response. Although p53 is a universal inducer of apoptotosis in many stress
      responses, including the genotoxic response, the role of nuclear factor (NF)
      kappaB is not consistent and was reported to both counteract and mediate
      apoptosis. Although the reason for the apparent contradictory effects of NF
      kappaB is not understood, it may partly be related to the reported cross
      regulation of NF-kappaB and p53. Thus far, all studies exploring the cross-talk
      between p53 and NF-kappaB in conjunction with apoptosis have been performed in
      tissue-cultured cells and may therefore not faithfully represent conditions that
      prevail within a chemotherapy-subjected organism. To address this concern, we
      examined the respective roles of NF-kappaB and p53 in a liver model of
      doxorubicin-induced DNA damage. Using this animal model, we report that NF-kappaB
      is activated in response to doxorubicin-induced genotoxic stress and exerts a
      pronounced protective effect in opposing chemotherapy-induced tissue damage.
      Importantly, the activation of NF-kappaB occurs independently of p53 status.
      Furthermore, although p53 is also induced in this in vivo system, its induction
      is independent of NF-kappaB and does not contribute to the extent of tissue
      damage. These findings may have important implications with respect to the
      potential use of NF-kappaB modulators in cancer therapy.

PMID- 12517773
TI  - The protein kinase C inhibitor Go6976 is a potent inhibitor of DNA damage-induced
      S and G2 cell cycle checkpoints.
AB  - In response to DNA damage, cells arrest progression through the cell cycle at
      either G(1), S, or G(2). We have reported that UCN-01 (7-hydroxystaurosporine)
      abrogates DNA damage-induced S and G(2) arrest and enhances cytotoxicity
      selectively in p53 mutant cells, thus providing a potential, tumor-targeted
      therapy. Unfortunately, UCN-01 binds avidly to human plasma proteins, limiting
      bioavailability. Because UCN-01 also inhibits protein kinase C (PKC), we screened
      other PKC inhibitors, expecting them to be unable to abrogate arrest. However,
      Go6976 potently abrogated S and G(2) arrest and enhanced the cytotoxicity of the
      topoisomerase I inhibitor SN38 only in p53-defective cells. Importantly, Go6976
      was nearly as potent at abrogating S and G(2) arrest in human serum, a property
      not possessed by UCN-01. Cell viability studies demonstrated that Go6976 was
      impressively nontoxic as a single agent. Analysis of proteins that regulate cell
      cycle arrest suggested that both drugs inhibit the checkpoint kinases Chk1 and/or
      Chk2. Additionally, Go6976 abrogated S and G(2) arrest at a concentration
      substantially lower than that required to inhibit PKC; UCN-01 did not demonstrate
      this selectivity for checkpoint inhibition. These properties make Go6976 a
      promising candidate for preclinical and clinical studies.

PMID- 12517774
TI  - Interphase cytogenetic abnormalities in chronic lymphocytic leukemia may predict
      response to rituximab.
AB  - Select cytogenetic abnormalities such as del(17)(p13.1) and del(11)(q22
      q23)predict rapid disease progression and inferior survival in chronic
      lymphocytic leukemia (CLL). We sought to determine the impact of the four most
      common interphase cytogenetic abnormalities in 28 CLL patients relative to
      response to three-times-a-week rituximab therapy. Abnormalities were noted in 25
      of the 28 patients to include del(13)(q14.3) [n = 16 (57%)], del(11)(q22.3) [n =
      10 (36%)], +12 [n = 6 (21%)], del(17)(p13.1) [n = 5 (18%)], and normal [n = 3
      (11%)]. Only a minority of each of these occurred as sole abnormalities. To
      categorize patients into one specific group, we used the hierarchical order
      del(17)(p13.1) > del(11)(q22.3) > trisomy 12 > del(13)(q14.3) to prioritize.
      Response to rituximab was noted to vary by cytogenetic group: del(17)(p13.1), 0%
      [n = 5]; del(11)(q22.3), 66% [n = 9]; del(13)(q14.3), 86% [n = 7]; +12, 25% [n =
      4], and normal, 0% [n = 3]. Response was significantly lower (P = 0.05) in
      patients with del(17)(p13.1) as compared with those with other abnormalities.
      These data suggest that interphase cytogenetics in CLL may be predictive of a
      response to rituximab therapy and provide support for additional studies
      validating risk-adapted therapy in this disease.

PMID- 12517775
TI  - Identification of ErbB-2 kinase domain motifs required for geldanamycin-induced
      degradation.
AB  - The ansamycin antibiotic geldanamycin (GA) induces the intracellular degradation
      of ErbB-2/neu. Degradation of ErbB-2 proceeds through cleavage(s) within the
      kinase domain, resulting in the formation of a 135 kDa ectodomain fragment and a
      fragment(s) of approximately 50 kDa containing the COOH-terminal region. On the
      basis of independent means of identification, two adjacent sequence motifs have
      been identified in ErbB-2 that are required for GA-induced degradation. These
      motifs encompass residues 776-783 and 784-786 within the NH(2)-terminal lobe of
      the ErbB-2 kinase domain. This is also a region in which the epidermal growth
      factor receptor and ErbB-2 kinase domains differ significantly in sequence.
      Although mutations in this region abrogate GA-induced ErbB-2 degradation, the
      tyrosine kinase activity of ErbB-2 is not disrupted. Interestingly, these ErbB-2
      mutants are specifically resistant to GA-induced degradation but retain
      sensitivity to other drugs, such as staurospore and curcumin, which are also able
      to provoke ErbB-2 degradation.

PMID- 12517776
TI  - NOVP chemotherapy for Hodgkin's disease transiently induces sperm aneuploidies
      associated with the major clinical aneuploidy syndromes involving chromosomes X,
      Y, 18, and 21.
AB  - The objective of this research was to determine whether Novantrone, Oncovin,
      Velban, and Prednisone (NOVP) combination chemotherapy for Hodgkin's disease
      increases the frequencies of the specific types of aneuploid sperm that might
      elevate the risk of fathering a child with one of the major clinical aneuploidy
      syndromes, i.e., Down (disomy 21 sperm), Edward (disomy 18 sperm), Turner
      (nullisomy sex sperm), XYY (disomy Y sperm), triple X (disomy X sperm), or
      Klinefelter (XY sperm). A four-chromosome multicolor sperm fluorescence in-situ
      hybridization assay that simultaneously evaluates chromosomes 18, 21, X, and Y
      was applied to semen provided by four healthy men and to repeated samples of
      eight Hodgkin's disease patients before treatment, 35-50 days after treatment to
      examine the effects of treatment on male meiotic cells, and 1-2 years after
      treatment to measure the persistence of damage. There were chromosome-specific
      variations in baseline frequencies and significant inductions of all of the
      detectable types of sperm aneuploidies: XY sperm (14-fold increase), disomy 18 (7
      fold), nullisomy sex (3-fold), disomy 21 (3-fold), and disomy X and Y
      (approximately 2-fold each). Disomy 21 was about twice as frequent as disomy 18,
      and neither showed a preferential segregation with a sex chromosome.
      Extrapolating across the genome, approximately 18% of sperm carried a numerical
      abnormality after NOVP treatment of meiotic cells. Induced effects did not
      persist to 1-2 years after treatment, suggesting that persistent spermatogonial
      stem cells were not sensitive to NOVP. These findings establish the hypothesis
      that conception shortly after certain chemotherapies can transiently increase the
      risks of fathering aneuploid pregnancies that terminate during development or
      result in the birth of children with major human aneuploidy syndromes.

PMID- 12517777
TI  - Delineation of the molecular basis for selenium-induced growth arrest in human
      prostate cancer cells by oligonucleotide array.
AB  - Despite the growing interest in selenium intervention of prostate cancer in
      humans, scanty information is currently available on the molecular mechanism of
      selenium action. Our past research indicated that methylseleninic acid (MSA) is
      an excellent reagent for investigating the anticancer effect of selenium in
      vitro. The present study was designed to examine the cellular and molecular
      effects of MSA in PC-3 human prostate cancer cells. After exposure to
      physiological concentrations of MSA, these cells exhibited a dose- and time
      dependent inhibition of growth. MSA retarded cell cycle progression at multiple
      transition points without changing the proportion of cells in different phases of
      the cell cycle. Flow cytometric analysis of annexin V- and propidium iodide
      labeled cells showed a marked induction of apoptosis by MSA. Array analysis with
      the Affymetrix human genome U95A chip was then applied to profile the gene
      expression changes that might mediate the effects of selenium. Gene profiling was
      done in a time course experiment (at 12, 24, 36, and 48 h) using synchronized
      cells. A large number of potential selenium-responsive genes with diverse
      biological functions were identified. These genes fell into 12 clusters of
      distinct kinetics pattern of modulation by MSA. The expression changes of 10
      genes known to be critically involved in cell cycle regulation were selected for
      verification by Western analysis to determine the reliability of the array data.
      An agreement rate of 70% was obtained based on these confirmation experiments.
      The array data enabled us to focus on the role of potential key genes (e.g.,
      GADD153, CHK2, p21(WAF1), cyclin A, CDK1, and DHFR) that might be targets of MSA
      in impeding cell cycle progression. The data also provide valuable insights into
      novel biological effects of selenium, such as inhibition of cell invasion, DNA
      repair, and stimulation of transforming growth factor beta signaling. The present
      study demonstrates the utility of a genome-wide analysis to elucidate the
      mechanism of selenium chemoprevention.

PMID- 12517778
TI  - Microarray reveals differences in both tumors and vascular specific gene
      expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas.
AB  - Malignant lymphoma is a heterogeneous disease with different clinical features.
      Among diffuse large B-cell lymphomas (DLBCLs), a unique subtype has been
      identified recently based on cell surface marker CD5 and clinicopathological
      features. These de novo CD5(+) DLBCLs account for approximately 10% of all of the
      DLBCLs and have poorer prognosis. To additionally understand this subtype of
      DLBCLs at the molecular level and to find genes that are differentially expressed
      in de novo CD5(+) DLBCLs, CD5(-) DLBCLs, and mantle cell lymphomas, which also
      have poor prognosis, we performed gene expression profiling using cDNA microarray
      technology. Data from a total of 9 samples of CD5(-) DLBCLs, 11 samples of de
      novo CD5(+) DLBCLs, and 10 samples of mantle cell lymphomas were acquired. A
      series of genes were identified that distinguish these three types of lymphomas.
      Among DLBCL cases, integrin beta1 and/or CD36 adhesion molecules were
      overexpressed in most cases of CD5(+) DLBCL. An immunohistochemical confirmation
      study revealed that integrin beta1 was expressed on lymphoma cells, which may
      account for the high extranodal involvement and poor prognosis of CD5(+) DLBCLs.
      In contrast, CD36 was overexpressed on vascular endothelia in CD5(+) DLBCLs,
      although there was no difference in vascularity detected by von Wilbrand factor
      antibody between CD5(+) and CD5(-) DLBCLs. Those results suggest that CD5(+) and
      CD5(-) DLBCLs have different gene expression signatures in both tumor cells and
      their vascular systems.

PMID- 12517779
TI  - Extracellular calcium and calcium sensing receptor function in human colon
      carcinomas: promotion of E-cadherin expression and suppression of beta
      catenin/TCF activation.
AB  - Ca(2+) has chemopreventive activity against colon cancer, albeit its mechanisms
      of action are not understood. In this study, we showed that four different human
      colon carcinoma cell lines (FET, SW480, MOSER, and CBS) expressed the human
      parathyroid calcium sensing receptor (CaSR) and that a function of extracellular
      Ca(2+) and the CaSR in these cells was the promotion of E-cadherin expression and
      suppression of beta-catenin/T cell factor activation. We also found that human
      colonic crypt epithelial cells expressed the CaSR, and histologically
      differentiated carcinomas (i.e., where three-dimensional, crypt-like structures
      were present) expressed less receptor by comparison, whereas an almost complete
      loss of CaSR expression was observed in undifferentiated tumors. These results
      suggest that extracellular Ca(2+) and the CaSR may function to regulate the
      differentiation of colonic epithelial cells and that disruption of this ligand
      receptor system may contribute to abnormal differentiation and malignant
      progression. In addition, the promotion of E-cadherin and suppression of beta
      catenin/T cell factor may be an important mechanism underlying the
      chemopreventive action of Ca(2+) in colon cancer.

PMID- 12517780
TI  - Immunotoxin resistance in multidrug resistant cells.
AB  - Multidrug resistance (MDR) can be mediated, in part, by overexpression of P
      glycoprotein (P-gp) and is characterized by broad resistance to several
      structurally, chemically, and pharmacologically distinct chemotherapeutic
      compounds. It has been hypothesized that immunological approaches to cytolysis
      may be used to overcome drug resistance. RV+ is a P-gp-expressing variant of the
      human myeloid leukemic cell line HL60 that displays a typical MDR phenotype. MDR
      RV+ cells displayed relative resistance to the immunotoxin (IT) HuM195-gelonin
      and to free rGelonin. K562 leukemia cells retrovirally infected to overexpress P
      gp are also resistant to HuM195-gelonin. In addition, a monoclonal antibody
      capable of inhibiting the function of P-gp was able to partially reverse
      resistance to the IT. These data indicated that the expression of P-gp may
      contribute to IT resistance in RV+. Resistance to the IT was not mediated through
      decreased binding to cells, nor reduced internalization into the cell because the
      IT displayed similar kinetics of binding and internalization for both the
      parental HL60 and MDR RV+ cell lines. Comparison of the cytotoxicity of other
      ribosome-inactivating toxins indicated that RV+ cells were not universally
      resistant to toxins: RV+ cells were sensitive to the actions of ricin A chain,
      which acts on precisely the same RNase target as gelonin. Sensitivity of the MDR
      RV+ cells to the protein synthesis inhibitor cycloheximide, saponin, and
      Pseudomonas exotoxin A additionally confirmed that the resistance was not
      mediated through the ribosome and that pathways downstream from the inactivation
      of protein synthesis leading to cell death were not substantially perturbed in
      the MDR cells. Resistance could be partially abrogated by bafilomycin A, which
      inhibits lysosomal function. Moreover, direct visualization by confocal
      microscopy of the intracellular trafficking route of the IT showed that the IT
      accumulated preferentially in the lysosome in MDR RV+ cells but not in sensitive
      cells. These observations implicated the process of increased lysosomal
      degradation as the most likely basis for resistance. Such pathways of resistance
      may be important in the therapeutic applications of ITs, now becoming available
      for human use.

PMID- 12517781
TI  - Efficacy of camptothecin analog DX-8951f (Exatecan Mesylate) on human pancreatic
      cancer in an orthotopic metastatic model.
AB  - We determined the antitumor and antimetastatic efficacy of the camptothecin
      analogue DX-8951f in an orthotopic metastatic mouse model of pancreatic cancer.
      DX-8951f showed efficacy against two human pancreatic tumor cell lines in this
      model. These cell lines were transduced with the green fluorescent protein,
      enabling high-resolution visualization of tumor and metastatic growth in vivo.
      The DX-8951f studies included both an early and advanced cancer model. In the
      early model, using the human pancreatic cancer lines MIA-PaCa-2 and BxPC-3,
      treatment began when the orthotopic primary tumor was approximately 7 mm in
      diameter. DX-8951f was significantly effective against both MIA-PaCa-2 and BxPC
      3. In contrast, 2', 2'-difluorodeoxycytidine (gemcitabine), the standard
      treatment for pancreatic cancer, did not have significant efficacy against MIA
      PaCa-2. Although gemcitabine showed significant activity against BxPC-3 primary
      tumor growth, it was not effective on metastasis. In the model of advanced
      disease, using BxPC-3, treatment started when the orthotopic primary tumor was 13
      mm in diameter. DX-8951f was significantly effective in a dose-response manner on
      the BxPC-3 primary tumor. DX-8951f also demonstrated antimetastatic activity in
      the late-stage model, significantly reducing the incidence of lymph node
      metastasis while eliminating lung metastasis. In contrast, gemcitabine was only
      moderately effective against the primary tumor and ineffective against metastasis
      at both sites in the late-stage model. Therefore, DX-8951f was highly effective
      against primary and metastatic growth in this very difficult-to-treat disease and
      showed significantly higher efficacy than gemcitabine, the standard treatment of
      pancreatic cancer. DX-8951f, therefore, has important clinical promise and has
      more positive features than the currently used camptothecin analogue CPT-11,
      which requires metabolic activation and is toxic.

PMID- 12517782
TI  - Doxorubicin-loaded Fab' fragments of anti-disialoganglioside immunoliposomes
      selectively inhibit the growth and dissemination of human neuroblastoma in nude
      mice.
AB  - Neuroblastoma (NB) is the most common extracranial solid tumor in children.
      Intensive therapeutic intervention does not prolong the overall disease-free
      survival rate for this tumor. NB tumor, but not normal tissues, overexpress the
      disialoganglioside (GD(2)) at the cell surface. Anti-GD(2) whole antibodies
      (aGD(2)) or their corresponding Fab' fragments were covalently coupled to Stealth
      immunoliposomes (aGD(2)-SIL or Fab'-SIL), and their binding to GD(2)-positive NB
      cells was measured. Cytotoxic effects of immunoliposomes loaded with doxorubicin
      (DXR) were determined. Radiolabelled immunoliposomes were used to evaluate
      pharmacokinetics (PK). The effectiveness of different liposomal formulations of
      DXR was tested against a metastatic model of human NB in nude mice. aGD(2)-SIL
      and Fab'-SIL showed concentration-dependent specific binding and uptake by GD(2)
      positive NB cells. DXR entrapped in aGD(2)-SIL or Fab'-SIL (aGD(2)-SIL[DXR], Fab'
      SIL[DXR]) showed higher cytotoxicities than nontargeted liposomes (SL[DXR]). DXR
      loaded Fab'-SIL (Fab'-SIL[DXR]) also showed specific binding, uptake, and
      cytotoxic effects on several GD(2)-positive NB cells in vitro. PK studies showed
      that Fab'-SIL had long-circulating profiles in blood compared with aGD(2)-SIL,
      with the PK profile for Fab'-SIL being almost identical to that obtained with
      nontargeted Stealth liposomes. In vivo, long-term survivors were obtained in mice
      treated with Fab'-SIL[DXR] but not in untreated animals, or those treated with
      free aGD(2) Fab', Fab'-SIL (no drug), free-DXR, or nontargeted Stealth
      liposomes[DXR] (no antibody; P < 0.0001). Immunoliposomes containing DXR
      prevented the establishment and growth of the tumor in all of the organs
      examined. In conclusion, Fab'-SIL[DXR] formulations led to the total inhibition
      of metastatic growth of human NB in a nude mouse metastatic model. This
      formulation should receive clinical evaluation as adjuvant therapy of NB.

PMID- 12517783
TI  - Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast
      cancer cells to epothilone B-induced apoptosis.
AB  - The molecular mechanisms underlying the cell cycle growth-inhibitory and
      apoptotic effects of flavopiridol (FP) were determined in human breast cancer
      cells. Treatment with FP caused accumulation in the G(1) phase of the cell cycle
      and induced apoptosis of SKBR-3 and MB-468 cells. This was associated with down
      regulation of the levels of cyclins D1 and B1, as well as with inhibition of
      cyclin-dependent kinase (cdk) 1, cdk2, and cdk4. FP-induced apoptosis was
      accompanied by a conformational change and mitochondrial localization of Bax.
      This resulted in the accumulations of cytochrome c, Smac, and Omi/HtrA2 in the
      cytosol and induced the poly(ADP-ribose) polymerase cleavage activity of caspase
      3. Treatment with FP also attenuated the mRNA and protein levels of XIAP, cIAP-2,
      Mcl-1, Bcl-x(L), and survivin. In MB-468 cells with overexpression of Bcl-2
      (468/Bcl-2), FP-induced Bax conformational change and apoptosis were inhibited,
      whereas the FP-mediated decline in the levels of IAP proteins, Mcl-11 and Bcl
      x(L) remained unaltered. The effects of cotreatment with FP and the nontaxane
      tubulin-polymerizing agent epothilone (Epo) B were also determined in MB-468
      cells. Sequential treatment with Epo B followed by FP induced significantly more
      apoptosis of MB-468 cells than treatment with the reverse sequence of FP followed
      by Epo B or treatment with either agent alone (P < 0.05). Treatment with Epo B
      followed by FP induced more Bax conformational change and was associated with a
      greater decline in the levels of XIAP, cIAP-2, Mcl-1, and Bcl-x(L). However, MB
      468/Bcl-2 cells remained relatively resistant to Epo B followed by FP. Taken
      together, these findings suggest that the superior sequence-dependent anti-breast
      cancer activity of Epo B followed by FP may be due to FP-induced Bax
      conformational change and down-regulation of the antiapoptotic IAP, Bcl-x(L), and
      Mcl-1 proteins, but this treatment may not overcome the resistance to apoptosis
      of breast cancer cells conferred by overexpression of Bcl-2.

PMID- 12517784
TI  - A nuclear protein complex containing high mobility group proteins B1 and B2, heat
      shock cognate protein 70, ERp60, and glyceraldehyde-3-phosphate dehydrogenase is
      involved in the cytotoxic response to DNA modified by incorporation of anticancer
      nucleoside analogues.
AB  - Thiopurine treatment of human leukemia cells deficient in components of the
      mismatch repair system (Nalm6) initiated apoptosis after incorporation into DNA,
      as revealed by caspase activation and terminal deoxynucleotidyl transferase
      mediated nick end labeling assay. To elucidate the cellular sensor(s) responsible
      for recognition of DNA damage in cells with an inactive mismatch repair system,
      we isolated a multiprotein nuclear complex that preferentially binds DNA with
      thioguanine incorporated. The components of this nuclear multiprotein complex, as
      identified by protein mass spectroscopy, included high mobility group proteins 1
      and 2 (HMGB1, HMGB2), heat shock protein HSC70, protein disulfide isomerase
      ERp60, and glyceraldehyde 3-phosphate dehydrogenase. The same complex was also
      shown to bind synthetic oligodeoxyribonucleotide duplexes containing the
      nonnatural nucleosides 1-beta-D-arabinofuranosylcytosine or 5-fluoro-2'
      deoxyuridine. Fibroblast cell line derived from Hmgb1(-/-) murine embryos had
      decreased sensitivity to thiopurines, with an IC(50) 10-fold greater than Hmgb1
      proficient cells (P < 0.0001) and exhibited comparable sensitivity to
      vincristine, a cytotoxic drug that is not incorporated into DNA. These findings
      indicate that the HMGB1-HMGB2-HSC70-ERp60-glyceraldehyde 3-phosphate
      dehydrogenase complex detects changes in DNA structure caused by incorporation of
      nonnatural nucleosides and is a determinant of cell sensitivity to such DNA
      modifying chemotherapy.

PMID- 12517785
TI  - Suppression of hormone-refractory prostate cancer by a novel nuclear factor
      kappaB inhibitor in nude mice.
AB  - We have synthesized and explored the feasibility of using a novel nuclear factor
      (NF) kappaB inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ,
      against prostate cancer. The activity of NFkappaB, evaluated by transient
      transfection of a luciferase reporter DNA containing a specific binding sequence
      for NFkappaB, was inhibited by DHMEQ in three human hormone-refractory prostate
      cancer cell lines, DU145, JCA-1, and PC-3. Statistically significant growth
      inhibition was achieved by 20 micro g/ml of DHMEQ, and marked levels of apoptosis
      were induced 48 h after DHMEQ administration in vitro. Electrophoretic mobility
      shift assay showed that DHMEQ completely inhibited NFkappaB DNA binding activity
      in JCA-1 cells. Furthermore, i.p. administrations of DHMEQ significantly
      inhibited pre-established JCA-1 s.c. tumor growth in nude mice without any side
      effects. Our result indicates the possibility of using a novel NFkappaB
      activation inhibitor, DHMEQ, as a new treatment strategy against hormone
      refractory prostate cancer.

PMID- 12517786
TI  - Improved iodine radiolabels for monoclonal antibody therapy.
AB  - A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for
      radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells
      after internalization and catabolism of the radioiodinated MAbs. We recently
      reported that a radioiodinated, diethylenetriaminepentaacetic acid-appended
      peptide, designated immunomedics' residualizing peptide 1 (IMP-R1), was a
      residualizing iodine label that overcame many of the limitations that had impeded
      the development of residualizing iodine for clinical use. To determine the
      factors governing the therapeutic index of the labeled MAb, as well as the
      factors required for production of radioiodinated MAb in high yield and with high
      specific activity, variations in the peptide structure of IMP-R1 were evaluated.
      A series of radioiodinated, diethylenetriaminepentaacetic acid-appended peptide
      moieties (IMP-R1 through IMP-R8) that differed in overall hydrophilicity and
      charge were compared. Radioiodinations of the peptides followed by conjugations
      to disulfide-reduced RS7 (an anti-epithelial glycoprotein-1 MAb) furnished
      radioimmunoconjugates in good overall incorporations, with immunoreactivities
      comparable to that of directly radioiodinated RS7. Specific activities of up to 8
      mCi/mg and yields > 80% have been achieved. In vitro processing experiments
      showed marked increases in radioiodine retention with all of the adducts;
      radioiodine retention at 45 h was up to 86% greater in cells than with directly
      iodinated RS7. Each of the (125)I-peptide-RS7 conjugates was compared with (131)I
      RS7 (labeled by the chloramine-T method) in paired-label biodistribution studies
      in nude mice bearing human lung tumor xenografts. All of the residualizing
      substrates exhibited significantly enhanced retention in tumor in comparison to
      directly radioiodinated RS7, but the nontarget uptakes differed significantly
      among the residualizing labels. The best labels were IMP-R4 and IMP-R8, showing
      superior tumor-to-non-tumor ratios by virtue of high tumor uptake and retention
      and low normal organ uptake, as well as superior radiochemical properties. The
      therapeutic efficacy of (131)I-IMP-R4-RS7 was compared with that of
      conventionally (131)I-labeled RS7 and (90)yttrium-RS7 in the nude mice lung
      cancer model. The therapeutic efficacy of (131)I-IMP-R4-RS7 and (90)yttrium-RS7
      were equivalent, and both agents yielded significantly improved control of tumor
      growth compared with conventional (131)I-labeled RS7.

PMID- 12517787
TI  - Identification of genes responsible for cell migration by a library of randomized
      ribozymes.
AB  - Several genes appear to be associated with metastasis, but the underlying
      mechanisms of metastasis still remain unclear. In this study, we used a library
      of randomized ribozymes to identify, by inactivation of transcripts, genes
      involved in cell migration that is an essential aspect of metastasis. Using a
      chemotaxis assay, the ribozymes that inhibited cell migration were selected from
      the library. Among such ribozymes, we found two ribozymes that targeted and
      cleaved ROCK1 mRNA at independent sites. ROCK1 and ROCK2 are Rho kinases, and it
      has been demonstrated that they regulate the organization of the actin
      cytoskeleton and are responsible for cell motility and cytokinesis. The two
      ribozymes that specifically cleaved ROCK1 mRNA inhibited both the migration and
      invasion of invasive HT1080 fibrosarcoma, but neither had any effect on cell
      proliferation. Our analysis indicates that the ribozymes toward ROCK1 can block
      invasive activity but not the proliferation of HT1080 cells without having any
      effect on expression of ROCK2. Ribozymes identified in this study, including the
      ribozymes against ROCK1, might be useful in understanding the mechanisms of cell
      migration and metastasis.

PMID- 12517788
TI  - Genetic analysis of three-dimensional shape of mouse lung tumors reveals eight
      lung tumor shape-determining (Ltsd) loci that are associated with tumor
      heterogeneity and symmetry.
AB  - Most lung tumor linkage studies focus on identifying loci that confer
      susceptibility or resistance irrespective of the tumor types developed. However,
      different mouse strains develop different types of lung tumors. A major obstacle
      for genetic studies of these differences is the lack of reproducible,
      quantitative, and uniform assessment of tumor type. We have previously described
      a new variable (Rratio) that assesses the three-dimensional shape of lung tumors
      in a quantifiable way and showed that nonspherical tumors are correlated with
      tumor heterogeneity and with a tendency to asymmetrical growth (N. Tripodis and
      P. Demant, Exp. Lung Res., 27: 521-531, 2001). In the present study, we use the
      Rratio variable to search for quantitative trait loci affecting tumor phenotype.
      We tested the F(2) cross between the susceptible strain O20 and the recombinant
      congenic strain OcB-9. Both develop mixed alveolar and papillary lung tumors, and
      the OcB9 tumors are, on average, more elongated than the O20 ones. We mapped
      eight new lung tumor shape-determining loci (Ltsd1-8) involved in mutual
      interactions. Two of these loci, Ltsd1 and Ltsd3, seem to play a major role in
      tumor shape formation. The Ltsd4 locus was confirmed in a second F(2) cross
      between strain O20 and the recombinant congenic strain OcB-6. Genotype-phenotype
      associations show that nonspherical tumors are correlated with tumor
      heterogeneity and nonsymmetrical (focal) development of structures. Most of the
      new Ltsd loci map in regions where susceptibility to lung cancer (Sluc) loci have
      been previously mapped, raising the question of whether they are identical or
      closely linked loci. Based on models of tumor growth indicating that supply of
      nutrients and the ability to create a capillary network may be shape-determining
      factors (G. P. Pescarmona et al., Med. Hypoth., 53: 497-503, 1999), we suggest as
      likely candidates for the Ltsd loci genes involved in angiogenesis,
      vascularization, and capillary patterning. This is the first set of loci that
      affects qualitative aspects of lung tumors and may provide biologically and
      clinically interesting indicators of lung tumor progression.

PMID- 12517789
TI  - Transcriptome analysis of HER2 reveals a molecular connection to fatty acid
      synthesis.
AB  - HER2 (erbB2/neu) is a member of the erbB family of receptor tyrosine kinases and
      is involved in regulating the growth of several types of human carcinomas. HER2
      represents a successful therapeutic target of the biotechnology era as
      exemplified by the drug Herceptin (trastuzumab), which has clinical activity in a
      subset of breast cancer patients. Using DNA microarrays, we identified a cohort
      of genes that are differentially regulated by HER2 in breast epithelial cells.
      One of the HER2-regulated genes discovered was fatty acid synthase (FAS), which
      has been shown to be overexpressed in breast cancer as well as other cancers. FAS
      is implicated in tumorigenesis through its role in cell proliferation and
      membrane lipid incorporation of neoplastic cells. Here, we demonstrate that HER2
      mediated induction of FAS is inhibitable by Herceptin and tyrosine kinase
      inhibitors of HER2. Through a phosphatidylinositol 3'-kinase-dependent pathway,
      HER2 stimulates the FAS promoter and ultimately mediates increased fatty acid
      synthesis. Interestingly, pharmacological inhibition of FAS preferentially
      induced apoptosis of HER2-overexpressing breast epithelial cells relative to
      matched vector control cells. These studies characterize a molecular connection
      between two genes individually implicated in tumorigenesis but never linked
      together.

PMID- 12517790
TI  - ERBB2 up-regulates S100A4 and several other prometastatic genes in
      medulloblastoma.
AB  - Medulloblastoma is frequently disseminated throughout the central nervous system
      by the time of diagnosis. Conventional therapeutic approaches have not reduced
      the high mortality associated with metastatic medulloblastoma and little is known
      regarding the molecular mechanisms that promote tumor invasion. Previously, we
      reported that overexpression of ERBB2 in medulloblastoma is associated with poor
      prognosis and metastasis. Here, we demonstrate that ERBB2 overexpression
      increases the migration of medulloblastoma cells across basement membranes in
      vitro. Furthermore, using microarray expression profiling, we show that ERBB2 up
      regulates the expression of prometastatic genes in medulloblastoma cells. These
      include S100A4, which was previously shown to promote metastasis of breast
      cancer. We demonstrate that S100A4 is a direct target of ERBB2 signaling in
      medulloblastoma cells via a pathway involving phosphatidylinositol 3-kinase,
      AKT1, and extracellular signal-regulated kinase 1/2 and that levels of ERBB2 and
      S100A4 are tightly correlated in samples of primary medulloblastoma. Finally, we
      show that ERBB2-dependent medulloblastoma cell invasion in vitro and
      prometastatic gene expression in vivo can be blocked using the ERBB tyrosine
      kinase inhibitor OSI-774. These data identify an ERBB2 driven prometastatic
      pathway that may provide a novel target for therapeutic intervention in
      metastatic medulloblastoma.

PMID- 12517791
TI  - Novel mutations of androgen receptor: a possible mechanism of bicalutamide
      withdrawal syndrome.
AB  - Most prostate cancers (PCs) become resistant to combined androgen blockade
      therapy with surgical or medical castration and antiandrogens after several
      years. Some of these refractory PCs regress after discontinuation of antiandrogen
      administration [antiandrogen withdrawal syndrome (AWS)]. Although the molecular
      mechanisms of the AWS are not fully understood because of the lack of suitable
      experimental models, one hypothesis of the mechanism is mutation of androgen
      receptor (AR). However, bicalutamide, which has become the most prevalent pure
      antiandrogen, does not work as an agonist for any mutant AR detected thus far in
      PC. To elucidate the mechanisms of the AWS, we established and characterized
      novel LNCaP cell sublines, LNCaP-cxDs, which were generated in vitro by culturing
      androgen-dependent LNCaP-FGC human PC cells in androgen-depleted medium with
      bicalutamide to mimic the combined androgen blockade therapy. LNCaP-FGC cells did
      not grow at first, but they started to grow after 6-13 weeks of culture.
      Bicalutamide stimulated LNCaP-cxD cell growth and increased prostate-specific
      antigen secretion from LNCaP-cxD cells both in vitro and in vivo. Sequencing of
      AR transcripts revealed that the AR in LNCaP-cxD cells harbors a novel mutation
      in codon 741, TGG (tryptophan) to TGT (cysteine; W741C), or in codon 741, TGG to
      TTG (leucine; W741L), in the ligand-binding domain. Transactivation assays showed
      that bicalutamide worked as an agonist for both W741C and W741L mutant ARs.
      Importantly, another antiandrogen, hydroxyflutamide, worked as an antagonist for
      these mutant ARs. In summary, we demonstrate for the first time that within only
      6-13 weeks of in vitro exposure to bicalutamide, LNCaP-FGC cells, whose growth
      had initially been suppressed, came to use bicalutamide as an AR agonist via W741
      AR mutation to survive. Our data strongly support the hypothesis that AR mutation
      is one possible mechanism of the AWS and suggest that flutamide might be
      effective as a second-line therapy for refractory PC previously treated with
      bicalutamide.

PMID- 12517792
TI  - EXO1 variants occur commonly in normal population: evidence against a role in
      hereditary nonpolyposis colorectal cancer.
AB  - Mutations in the currently known mismatch repair genes cannot explain all cases
      of hereditary nonpolyposis colorectal cancer (HNPCC), and novel predisposing
      genes are actively sought. Recently, mutations in the DNA repair gene EXO1 have
      been implicated in HNPCC. One truncating and several missense changes were
      observed in familial colorectal cancer (CRC) cases but not in controls. We
      evaluated a series of European CRC patients and population controls to clarify
      whether EXO1 variants may indeed predispose to familial CRC. Several variants
      observed in patients were also observed in controls with similar frequencies,
      including the truncating variant proposed previously to be a disease-causing
      mutation. Thus, little evidence was obtained to support a major causative role of
      EXO1 in HNPCC, although we cannot exclude a role for EXO1 as a low penetrance
      cancer susceptibility or modifying gene.

PMID- 12517793
TI  - Paradoxical effects of thiol reagents on Jurkat cells and a new thiol-sensitive
      mutant form of human mitochondrial superoxide dismutase.
AB  - The imbalance between oxidants and antioxidants in cells often results in
      pathological processes and/or diseases. This delicate balance is achieved in part
      by antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide
      dismutase (SOD), as well as by low-molecular-weight reductants such as
      glutathione. We evaluated the effect of thiol reagents on the proliferation of
      the Jurkat human T-cell leukemia-derived cell line. The cells show a multiphasic
      behavior when grown in the presence of thiols. Low concentrations of N-2
      mercaptopropionyl glycine (0.03 mM) cause growth arrest, and intermediate
      concentrations (0.3-1.0 mM) induce apoptosis. Similarly, 1 mM N-acetylcysteine or
      glutathione induce apoptosis in more than 40% of the cells. Surprisingly, the
      cells grow well in higher concentrations (3-10 mM) of these reagents. Because the
      I58T variant of human SOD2 is thiol-sensitive, we measured SOD in Jurkat cells
      grown in the presence of thiol agents, observing markedly less SOD activity. In
      cell-free extracts, thiols quickly eliminated the SOD2 activity. Jurkat cells
      contain little SOD2 activity, with a different electrophoretic mobility from that
      of normal lymphocytes. Single-strand conformational polymorphism analysis of the
      Jurkat sod2 gene revealed a pattern different from the wild-type gene, suggesting
      a mutation in the sod2 gene. This was confirmed by cloning and sequencing the
      gene. Jurkat cells are heterozygous for a new mutation, L60F, in exon 3 of the
      mature protein. Our findings suggest a possible association between decreased
      SOD2 activity and malignant phenotype.

PMID- 12517794
TI  - Identification of new drug sensitivity genes using genetic suppressor elements:
      protein arginine N-methyltransferase mediates cell sensitivity to DNA-damaging
      agents.
AB  - Genetic suppressor elements (GSEs) are cDNA fragments encoding either truncated
      proteins, acting as dominant-negative mutants, or inhibitory antisense RNA
      segments counteracting with the gene from which they are derived. To identify
      genes controlling the cell response to cytotoxic agents, a normalized retroviral
      library of randomly fragmented cDNAs from Chinese hamster cell line DC-3F was
      screened for GSEs conferring resistance to the topoisomerase II inhibitor 9-OH
      ellipticine. From 218 cDNA fragments isolated, 11 functional GSEs, corresponding
      to at least 8 independent genes, were selected. The gene corresponding to the
      most abundant GSE encodes two proteins, p77 and p82, highly homologous to
      proteins detected in various species and carrying the sequence motifs
      characteristic of the protein arginine N-methyltransferase family. Furthermore, a
      methylase activity was observed on myelin basic protein in immunoprecipitates of
      hemagglutinin-tagged p77 and p82. Therefore, p77 and p82 are the first identified
      members of a new protein arginine N-methyltransferase family. A decreased
      expression of these enzymes is associated with either resistance or
      hypersensitivity to a broad range of DNA-damaging agents. Our data indicate that
      down-regulation of these enzymes in the GSE-expressing cells would alter one or
      several steps downstream of the drug-target interaction in the drug-response
      pathway.

PMID- 12517795
TI  - Role of apical caspases and glucocorticoid-regulated genes in glucocorticoid
      induced apoptosis of pre-B leukemic cells.
AB  - Glucocorticoid (GC) sensitivity in hematopoietic cells requires the activation
      and nuclear translocation of the glucocorticoid receptor (GR) and the subsequent
      activation of caspases. To gain insight into the caspase cascade responsible for
      the execution phase of GC-induced apoptosis, 697 pre-B leukemic cells were stably
      transfected with dominant negative forms of caspase-8, caspase-9, or caspase-10
      and the caspase-8 inhibitor CrmA. We observed that inhibition of caspase-9 or
      caspase-10 activity, but not caspase-8, caused partial resistance of 697 cells to
      GC-induced apoptosis. Inhibition of multiple caspases through the use of specific
      peptide inhibitors had an additive effect and caused complete resistance. To
      identify GR-regulated genes upstream of caspase activation in 697 cells, we
      performed DNA microarray analysis. 113 genes were identified, which were induced
      or repressed at least 3-fold by GC. Surprisingly, mitogen-activated protein
      kinase phosphatase-1 (MKP-1), a GR-induced gene in other cell types, was
      repressed 3-fold and correlated with an induction of JNK activity. These results
      suggest the involvement of mitogen activated protein kinases and apical caspase-9
      and caspase-10 in the GC-induced apoptosis of pre-B lymphocytes.

PMID- 12517796
TI  - Allelic loss of p53 gene is associated with genesis and maintenance, but not
      invasion, of mouse carcinoma in situ of the bladder.
AB  - Carcinoma in situ (CIS) of the bladder has recently been proposed to be a
      heterogeneous group of diseases with varied histogenesis and biological behavior.
      In this study, we describe the sequential steps of CIS development and
      progression in a transgenic mouse model expressing low levels of the SV40 large T
      antigen. We found that CIS in transgenic mice arose from urothelial dysplasia,
      that CIS could persist for an extended period of time without invasion, and that
      the majority of CIS eventually evolved into high-grade, superficial, papillary
      tumors before a small fraction of them advanced to invasion/metastasis. A genome
      wide search of chromosomal imbalances by comparative genomic hybridization
      revealed that 9 of 11 (82%) of CIS had losses on chromosome 11. Southern blotting
      demonstrated the allelic loss of the p53 gene, which resides on mouse chromosome
      11, in four comparative genomic hybridization-tested tumors and 10 of 11 (91%)
      additional CIS examined. Consistent with the reduced p53 gene dosage because of
      the allelic loss and the functional inactivation of p53 protein of the remaining
      allele by SV40T antigen, there was a dramatic decrease in CIS of Mdm-2, a major
      p53 target. In contrast, the level of p21, another p53 target, was largely
      unaltered, suggesting that p21 expression can be regulated by p53-independent
      mechanisms. These results delineate the early stages of bladder tumorigenesis and
      suggest that the loss of a p53-bearing chromosome is an early event in bladder
      tumorigenesis and is crucial for the genesis and the maintenance, but not the
      progression, of bladder CIS. On the basis of our current and previous transgenic
      studies, we have proposed an integrated pathway progression model of bladder
      cancer.

PMID- 12517797
TI  - p53 deficiency accelerates induction and progression of esophageal and
      forestomach tumors in zinc-deficient mice.
AB  - The p53 tumor suppressor protein plays a pivotal role in preventing uncontrolled
      cellular proliferation. By contrast, zinc deprivation enhances esophageal cell
      proliferation and the induction of esophageal tumors in rodents by N
      nitrosomethylbenzylamine (NMBA). We investigated whether p53 deficiency rendered
      zinc-deficient (ZD) mice more susceptible to NMBA-induced esophageal/forestomach
      carcinogenesis. At 6-7 weeks of age, p53 null (-/-), heterozygous (+/-), and wild
      type (+/+) mice were placed on ZD or zinc-sufficient (ZS) diets to form six
      experimental groups: ZD:p53-/-; ZD:p53+/-; ZD:p53+/+; ZS:p53-/-; ZS:p53+/-; and
      ZS:p53+/+. After 3 weeks, 15-23 mice in each group were treated once with NMBA (2
      mg/kg body weight). Control animals were untreated. Zinc deficiency alone induced
      unrestrained cellular proliferation in the esophagus and forestomach of p53-/-
      mice. Forestomach tumors were first detected in a ZD:p53-/- mouse at 13 days. By
      30 days, 100% (21 of 21) of ZD:p53-/- mice developed forestomach tumors and 38%
      showed esophageal tumors versus 42 and 0% in ZS:p53-/- mice (P < 0.004,
      esophagus; P < 0.001, forestomach). ZD:p53-/- mice showed an accelerated
      progression to malignancy, with 10% of esophageal tumors and 38% of forestomach
      tumors presenting as carcinomas. Nearly 20% of ZD:p53-/- mice developed
      esophageal Barrett's metaplasia, a lesion not previously seen in NMBA-induced
      neoplasia. ZD:p53+/- mice had significantly higher tumor incidence than ZS:p53+/-
      mice. The order of tumor incidence in forestomach was as follows: naught
      incidence in ZS:p53+/+ mice; ZD:p53-/- > ZD:p53+/- > ZS:p53-/- > ZD:p53+/+ >/=
      ZS:p53+/- > ZS:p53+/+. The rapid rate of tumor induction/progression in ZD:p53-/-
      mice was accompanied by an increase in the rate of cell proliferation and a
      decrease in apoptosis. cDNA array expression analysis of known genes identified a
      5-fold up-regulation of cytokeratin 14 mRNA expression in ZD:p53-/- versus ZS:p53
      /- forestomach, a result showing gene-modulating effects of zinc deficiency.
      Cytokeratin 14 is a biomarker in human esophageal carcinogenesis. Our findings
      provide in vivo evidence for the collaboration of a deficiency of both p53 and
      zinc in esophageal carcinogenesis and reveal molecular targets of this
      collaboration.

PMID- 12517798
TI  - Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1
      integrins, increased invasion, and metastasis of human breast and ovarian cancer
      cells.
AB  - To determine how AKT2 might contribute to tumor cell progression, a full-length,
      wild-type, human AKT2/protein kinase B (PKB)beta cDNA was transfected into a
      panel of eight human breast and ovarian cancer cells. AKT2 transfectants
      demonstrated increased adhesion and invasion through collagen IV because of up
      regulation of beta1 integrins. In addition, AKT2 cells were more metastatic than
      control cells in vivo. Increased invasion by AKT2 was blocked by preincubation
      with an anti-beta1 integrin function blocking antibody, exposure to wortmannin,
      and by expression of phosphatase and tensin homologue tumor suppressor (PTEN).
      Confocal microscopy performed on transfected human breast cancer cells showed
      that unlike AKT1, AKT2 protein predominantly localized adjacent to the collagen
      IV matrix during cellular attachment. Overexpression of AKT2, but not AKT1 or
      AKT3, was sufficient to duplicate the invasive effects of phosphoinositide 3-OH
      kinase (PI3-K) transfected in breast cancer cells. Furthermore, expression of
      kinase dead AKT2(181 amino acid methionine [M]), and not kinase dead AKT1(179M)
      or AKT3(177M), was capable of blocking invasion induced by either human epidermal
      growth factor receptor-2 (HER-2) overexpression or by activation of PI3-K. Taken
      together, these data indicate that AKT2 mediates PI3-K-dependent effects on
      adhesion, motility, invasion, and metastasis in vivo.

PMID- 12517799
TI  - Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an
      important endogenous mechanism for resistance to liver metastases in murine renal
      cancer.
AB  - Recent reports have suggested that the death ligand tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) may partially limit the formation of hepatic
      metastases of a variety of mouse tumors, and the major source of TRAIL in the
      liver was shown to be local natural killer cells. We isolated a clone (R331) of
      the murine renal cancer cell line Renca that was strikingly more sensitive to
      both Fas and TRAIL death receptor-mediated apoptosis in vitro. R331 grew in
      tissue culture in vitro at a rate similar to that of the parental Renca cell line
      but formed larger and more numerous colonies than parental Renca in soft agar.
      After s.c. implantation, R331 tumors progressed more rapidly than parental Renca
      tumors. However, R331 formed far fewer lung and liver metastases in wild-type
      (WT) BALB/c mice. Administration of antibodies that neutralized TRAIL
      dramatically increased the number of R331 liver metastases. Furthermore, numbers
      of R331 liver metastases were much greater in TRAIL(-/-) than in WT BALB/c mice.
      In contrast, no difference was seen in numbers of lung metastases when comparing
      TRAIL(-/-) and WT mice, suggesting that the antitumor effects of TRAIL in vivo
      were compartment specific. Transfection of cellular Fas-associated death domain
      like interleukin-1beta-converting enzyme inhibitory protein into R331 increased
      the numbers of liver metastases in BALB/c mice by up to 10-fold, indicating that
      local TRAIL in the liver was directly mediating tumor cell apoptosis. These organ
      specific differences in the endogenous levels of death ligands may apply
      different selective pressures on the development of liver or lung metastases.
      Consequently, the efficacy of TRAIL therapy may vary depending on the location of
      the tumor metastases.

PMID- 12517800
TI  - Acetylcholine is synthesized by and acts as an autocrine growth factor for small
      cell lung carcinoma.
AB  - It is well established that small cell lung carcinomas (SCLCs) express receptors
      for acetylcholine (ACh) and that stimulation of these receptors by nicotine or
      other cholinergic agonists stimulates cell growth via activation of nicotinic
      cholinergic receptors (nAChRs) and/or muscarinic cholinergic receptors (mAChRs).
      The aim of this study was to determine whether SCLC cells synthesize and secrete
      ACh and respond to endogenous ACh to create a functioning cholinergic autocrine
      loop. Reverse transcription-PCR was used to screen a panel of SCLC cell lines for
      components of cholinergic signaling. Choline acetyltransferase (ChAT) and the
      vesicular ACh transporter (VAChT), as well as alpha3, alpha5, alpha7, beta2, and
      beta4, nAChR subunits and M3 and M5 mAChRs, were found to be present in most of
      the SCLC cell lines tested. Real-time PCR showed that mRNA levels for ChAT,
      VAChT, and alpha7 and beta2 nAChR subunits varied significantly among different
      SCLC cell lines tested. The H82 cell line was found to express the highest levels
      of ChAT, and that cell line was chosen for additional studies of ACh release and
      cell proliferation. ACh was easily detectable in H82 cell culture media, and
      levels of ACh were increased by the acetylcholinesterase inhibitor neostigmine.
      Vesamicol, an inhibitor of VAChT, and hemicholinium-3, an inhibitor of choline
      transport, both reduced H82 cell ACh basal release in a dose-dependent manner. In
      parallel with the reductions of ACh release, vesamicol and hemicholinium-3 also
      decreased H82 cell proliferation. H82 cell proliferation was also inhibited by
      the muscarinic and nicotinic antagonists atropine and mecamylamine, respectively,
      in dose- and time-dependent manners. Finally, archival cases of SCLC were
      screened by immunohistochemistry for expression of ChAT. Thirteen of 26 tumors
      screened were positive for ChAT. These findings demonstrate that SCLC can
      synthesize, secrete, and degrade ACh and that released ACh stimulates SCLC cell
      growth. Identification of this new autocrine loop provides a potential new target
      for therapeutic intervention.

PMID- 12517801
TI  - Laminin gamma2-chain fragment in the circulation: a prognostic indicator of
      epithelial tumor invasion.
AB  - Laminin (LN) 5, the major component of epithelial-derived extracellular matrix
      (ECM), plays a major role in cell adhesion and motility. Previous reports stated
      that proteolytic processing of the NH(2)-terminal region of the gamma2 chain
      enhances cell motility on LN5, indicating that the degraded gamma2 chain NH(2)
      terminal region would be shed from the ECM. However, soluble LN gamma2 NH(2)
      terminal fragment (G2F) have not been detected in biological fluids. Here, we
      developed a double-monoclonal electrochemiluminescence immunoassay for human G2F
      and detected its presence in the normal human circulation (mean +/- SD: 39.2 +/-
      10.3 ng/ml; n = 10). We also measured serum levels of G2F in nude mice
      orthotopically transplanted with three different human pancreatic carcinoma cell
      lines: MIApaca-II (secreting no LN5), HPAC (secreting the alpha3beta3gamma2
      heterotrimer of LN5), or KP-1 (secreting the monomeric gamma2 chain of LN5).
      Serum levels of G2F drastically increased in the nude mice transplanted with HPAC
      (mean +/- SD: 351 +/- 33 ng/ml, 5 weeks after transplantation), the most invasive
      tumor cells to generate extensive peritoneal dissemination in vivo. A moderate
      increase in serum levels of G2F was also observed in mice transplanted with KP-1
      (87.9 +/- 82 ng/ml, 5 weeks after transplantation), but no antigen was detected
      in the sera of MIApaca-II-transplanted mice. Therefore, circulating G2F was
      demonstrated to be a sensitive marker for LN5 production of primary pancreatic
      carcinomas, even if it was produced only as a monomeric gamma2 chain. In 11
      established human pancreatic tumor cell lines (6 of LN5-producing cells and 5 of
      nonproducing cells), LN5-secreting cells have significantly higher levels of cell
      surface expression of beta4 integrin than nonsecreting cells. Thus, LN5 secretion
      is accompanied by cell surface expression of alpha6beta4 integrin, participating
      in hemidesmosome reorganization to form invading edges of malignant epithelial
      carcinomas. These data reveal that the level of circulating G2F is a new,
      prognostic, tumor-characterizing marker for estimating the invasiveness and
      malignancy of epithelial carcinomas in cancer patients.

PMID- 12517802
TI  - Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor
      cell apoptosis.
AB  - Survivin is a member of the inhibitor of apoptosis gene family that is expressed
      in most human cancers and may facilitate evasion from apoptosis and aberrant
      mitotic progression. Here, exposure of breast carcinoma MCF-7 or cervical
      carcinoma HeLa cells to anticancer agents, including Adriamycin, Taxol, or UVB
      resulted in a 4-5-fold increased survivin expression. Changes in survivin levels
      after anticancer treatment did not involve modulation of survivin mRNA expression
      and were independent of de novo gene transcription. Conversely, inhibition of
      survivin phosphorylation on Thr(34) by the cyclin-dependent kinase inhibitor
      flavopiridol resulted in loss of survivin expression, and nonphosphorylatable
      survivin Thr(34)-->Ala exhibited accelerated clearance as compared with wild-type
      survivin. Sequential ablation of survivin phosphorylation on Thr(34) enhanced
      tumor cell apoptosis induced by anticancer agents independently of p53 and
      suppressed tumor growth without toxicity in a breast cancer xenograft model in
      vivo. These data suggest that Thr(34) phosphorylation critically regulates
      survivin levels in tumor cells and that sequential ablation of p34(cdc2) kinase
      activity may remove the survivin viability checkpoint and enhance apoptosis in
      tumor cells.

PMID- 12517803
TI  - PTEN mutation and epidermal growth factor receptor activation regulate vascular
      endothelial growth factor (VEGF) mRNA expression in human glioblastoma cells by
      transactivating the proximal VEGF promoter.
AB  - Our previous work showed that, compared with parental U87MG human glioblastoma
      cells, vascular endothelial growth factor (VEGF) mRNA levels are decreased in
      U87/T691, a derivative line in which epidermal growth factor receptor (EGFR)
      signaling is inhibited by introduction of a truncated p185(Neu) protein (A. Maity
      et al., Cancer Res., 60: 5879-5886, 2000). The effect of EGFR activation on VEGF
      was mediated at the level of transcription via a phosphatidylinositol 3'-kinase
      (PI3K)-dependent pathway. In the current study we investigated the effect of
      PTEN, a negative regulator of PI3K signaling commonly mutated in glioblastoma
      cells, on VEGF expression. Several glioblastoma cell lines containing mutant
      PTEN, including U87MG, U87/T691, and U251MG, were infected with adenovirus
      expressing wild-type PTEN. This led to a decrease in the levels of both VEGF mRNA
      and phosphorylated Akt, a marker for PI3K activation. Treatment of U87MG cells
      with LY294002, a PI3K inhibitor, or cotransfection with a vector expressing wild
      type PTEN decreased VEGF promoter activity using reporters containing either 1.5
      kb of the promoter or a fragment extending from -88 to +54 bp. Activity of the 
      88/+54 VEGF promoter was down-regulated by dominant negative Akt and up-regulated
      by constitutively active myristoylated Akt. Introduction of wild-type PTEN and
      pharmacological inhibition of EGFR decreased VEGF mRNA expression and VEGF
      promoter activity in U87MG cells to a greater extent that did either manipulation
      by itself. Therefore, in human glioblastoma cells, PTEN mutation can cooperate
      with EGFR activation to increase VEGF mRNA levels by transcriptionally up
      regulating the proximal VEGF promoter via the PI3K/Akt pathway.

PMID- 12517804
TI  - Overexpression of the autocrine motility factor/phosphoglucose isomerase induces
      transformation and survival of NIH-3T3 fibroblasts.
AB  - Autocrine motility factor (AMF)/phosphoglucose isomerase (PGI) is a ubiquitous
      cytosolic enzyme and is produced as a leaderless secretory protein, released from
      cells via a nonclassical pathway. AMF/PGI acts extracellularly as a potent
      mitogen/cytokine (CXXC, chemokine). Increased expression of AMF/PGI and its
      receptor/CXXC-R has been found in a wide spectrum of malignancies, and is
      associated with cancer progression and metastasis. To directly elucidate the
      functional role of AMF/PGI on cell motility and neoplastic transformation, we
      stably transfected AMF/PGI cDNA into NIH-3T3 cells. Ectopic overexpression of
      AMF/PGI results in its secretion and activation via a constitutive autocrine
      activation loop that renders the cells highly motile, acquiring a transformed
      phenotype in vitro and tumorigenicity in vivo. The transformed phenotype of
      AMF/PGI-transfected cells leads in part resistance to induction of apoptosis
      induced by serum starvation, through the activation of phosphatidylinositol 3'
      kinase/Akt signaling pathway and down-regulation of caveolin-1 expression.
      Overexpression of this housekeeping gene induces resistance to apoptosis and
      neoplastic transformation, and, thus, AMF/PGI represents a novel class of
      oncogenic protein.

PMID- 12517805
TI  - Constitutively active forms of c-Jun NH2-terminal kinase are expressed in primary
      glial tumors.
AB  - The c-Jun NH(2)-terminal kinases (JNKs) have a role both in promoting apoptosis
      and tumorigenesis. The JNKs are encoded by three separate genes (JNK1, 2, and 3),
      which are spliced alternatively to create 10 JNK isoforms that are either M(r)
      55,000 or 46,000 in size. However, the functional significance and distinct role
      for each splice variant remains unclear. We have noted previously that 86% of
      primary human glial tumors show activation of almost exclusively the M(r) 55,000
      isoforms of JNK. To further study which isoforms are involved, we constructed
      glutathione S-transferase fusion proteins for all 10 JNK isoforms and examined
      kinase activity with or without the activating upstream kinase. Surprisingly,
      five JNK isoforms demonstrate autophosphorylation activity, and in addition, all
      four JNK2 isoforms (either M(r) 55,000 or 46,000) show a high basal level of
      substrate kinase activity in the absence of the upstream kinase, especially a
      M(r) 55,000 JNK2 isoform. Examination revealed autophosphorylation activity at
      the T-P-Y motif, which is critical for JNK activation, because a mutant lacking
      the dual phosphorylation sites did not show autophosphorylation or basal kinase
      activity. Using green fluorescence protein-JNK expression vectors, transient
      transfection into U87MG cells demonstrates that although the JNK1 isoforms
      localize predominantly to the cytoplasm, the JNK2 isoforms localize to the
      nucleus and are phosphorylated, confirming the constitutive activation seen in
      vitro. We then examined which JNK isoforms are active in glial tumors by
      performing two-dimensional electrophoresis. This revealed that the M(r) 55,000
      isoforms of JNK2 are the principal active JNK isoforms present in tumors.
      Collectively, these results suggest that these constitutively active JNK isoforms
      play a significant role in glial tumors. Aside from epidermal growth factor
      receptor vIII, this is the only other kinase that has been shown to be basally
      active in glioma. The presence of constitutively active JNK isoforms may have
      implications for the design of inhibitors of the JNK pathway.

PMID- 12517806
TI  - Regulation of matrix metalloproteinase-1 by Epstein-Barr virus proteins.
AB  - Matrix metalloproteinases (MMPs) play crucial roles in tumor progression. To
      investigate the roles of MMPs in the progression of nasopharyngeal carcinoma
      (NPC), the expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-12, MMP-13, MMP-14, and
      MMP-19 was explored by microarray assay. Among them, MMP-1 was significantly up
      regulated in NPC biopsies. These results were confirmed further by real-time
      quantitative PCR in additional NPC biopsies and comparison with normal tissues
      and other head and neck cancers. Moreover, the use of RNA from different cellular
      constituents of NPC biopsies revealed that MMP-1 was detected predominantly in
      epithelial cells. Immunohistochemical staining of paraffin-fixed NPC sections
      confirmed that MMP-1 protein was expressed in the epithelial tumor cells. Because
      EBV is strongly associated with NPC formation, we sought a correlation between
      viral gene expression and MMP-1 up-regulation. The results showed clearly that
      the amounts of transcripts, proteins, and enzyme activities of MMP-1 were
      increased in cells expressing EBV proteins, LMP1 (latent membrane protein 1) and
      Zta (Z transactivator; also named as BZLF1 or ZEBRA) but not EBNA-1 (EBV nuclear
      antigen-1). Additionally, the mobility of LMP1 and Zta transfectants was
      increased in scrape-wound migration assays. The invasiveness and ability to
      survive in a three-dimensional collagen gel also were enhanced in LMP1- and Zta
      expressing cells. Furthermore, anti-MMP-1 antibody and peptide inhibitors could
      block the invasiveness and survival properties of LMP1 and Zta transfectants,
      suggesting a real contribution of MMP-1 to cell mobility and survival. Taken
      together, our data show that the viral LMP1 and Zta proteins regulate the
      expression and activity of MMP-1, and thereby confer the invasive properties of
      the cells. This study presents the first evidence that viral proteins are capable
      of regulating MMP-1 and also provides clues for the role of EBV in NPC
      progression.

PMID- 12517808
TI  - Thromboembolic events in children with acute lymphoblastic leukemia (BFM
      protocols): prednisone versus dexamethasone administration.
AB  - Alterations in hemostasis leading to symptomatic thromboembolism have been
      observed in patients with acute lymphoblastic leukemia (ALL) receiving
      Escherichia coli asparaginase (CASP) combined with steroids. Moreover, hereditary
      prothrombotic risk factors are associated with an increased risk for venous
      thromboembolism in pediatric ALL patients treated according to the BFM 90/95
      protocols (including CASP combined with prednisone during induction therapy). To
      assess whether the thromboembolic risk associated with established prothrombotic
      risk factors is modified by treatment modalities (prednisone or dexamethasone),
      the present analysis was performed. Three hundred thirty-six consecutively
      recruited leukemic children treated according to different BFM protocols (PRED
      group, n = 280, 60 mg/m(2) prednisone; DEXA group, n = 56, 10 mg/m(2)
      dexamethasone during induction therapy) were studied. Study end point was the
      onset of symptomatic vascular accidents during induction therapy. Cumulative
      thromboembolism-free survival was significantly reduced in children in the PRED
      group (thrombosis frequency, 10.4%) compared with children in the DEXA group
      (thrombosis frequency, 1.8%; P =.028). Although no significant difference was
      found in the overall prevalence of prothrombotic risk factors, 46.5% of patients
      in the PRED group who experienced thromboembolic events were carriers of a
      prothrombotic risk factor, whereas no carrier in the DEXA group had a
      thromboembolism. At the time of maximum CASP activity, fibrinogen and activities
      of antithrombin, plasminogen, and protein S were significantly reduced in the
      PRED group. No significant correlation could be found between CASP activity and
      levels of coagulation factors. In conclusion, the use of dexamethasone instead of
      prednisone, administered with CASP, significantly reduced the onset of venous
      thromboembolism.

PMID- 12517809
TI  - Lactadherin inhibits enzyme complexes of blood coagulation by competing for
      phospholipid-binding sites.
AB  - Lactadherin, a glycoprotein of the milk-fat globule membrane, contains tandem C
      domains with homology to discoidin-type lectins and to membrane-binding domains
      of blood-clotting factors V and VIII. We asked whether the structural homology
      confers the capacity to compete for the membrane-binding sites of factor VIII and
      factor V and to function as an anticoagulant. Our results indicate that
      lactadherin competes efficiently with factor VIII and factor V for binding sites
      on synthetic phosphatidylserine-containing membranes with half-maximal
      displacement at lactadherin concentrations of 1 to 4 nM. Binding competition
      correlated to functional inhibition of factor VIIIa-factor IXa (factor Xase)
      enzyme complex. In contrast to annexin V, lactadherin was an efficient inhibitor
      of the prothrombinase and the factor Xase complexes regardless of the degree of
      membrane curvature and the phosphatidylserine content. Lactadherin also inhibited
      the factor VIIa-tissue factor complex efficiently whereas annexin V was less
      effective. Because the inhibitory concentration of lactadherin was proportional
      to the phospholipid concentration, and because lactadherin was not an efficient
      inhibitor in the absence of phospholipid, the major inhibitory effect of
      lactadherin relates to blocking phospholipid sites rather than forming inhibitory
      protein-protein complexes. Lactadherin was also an effective inhibitor of a
      modified whole blood prothrombin time assay in which clotting was initiated by
      dilute tissue factor; 60 nM lactadherin prolonged the prothrombin time 150%
      versus 20% for 60 nM annexin V. These results indicate that lactadherin can
      function as a potent phospholipid-blocking anticoagulant.

PMID- 12517810
TI  - Distinct HLA associations by stroke subtype in children with sickle cell anemia.
AB  - Children with sickle cell anemia (SCA) carry a 200-fold increased risk for
      cerebral infarction. Stroke can be the result of small-vessel (SV) or large
      vessel (LV) disease. However, it is unknown whether these subtypes result from
      the same pathophysiologic processes. Complete HLA genotyping was performed on 231
      eligible children previously enrolled in the Cooperative Study of Sickle Cell
      Disease (CSSCD). Cerebral infarction on magnetic resonance imaging (MRI) was
      documented in 71 patients, and 160 patients had negative findings on MRI. Based
      on MRI/magnetic resonance angiography (MRA) findings, infarct size, and location,
      36 patients were classified as having LV stroke and 35 as having SV stroke. When
      comparing the total MRI+ group with the MRI- group, HLA DPB1*0401 was associated
      with increased stroke risk (P =.01), whereas DPB1*1701 (P =.02) conferred
      protection from stroke. These DPB1 associations with stroke were attributed to
      the SV stroke group, in whom DPB1*0401 was associated with susceptibility (P
      =.003) and DPB1*1701 with protection from stroke (P =.06). In the LV stroke
      subgroup, HLA-A*0102 (P =.02) and -A*2612 (P =.007) conferred susceptibility,
      whereas -A*3301(P =.04) protected from stroke. These results suggest that
      specific HLA alleles influence stroke risk and appear to contribute differently
      to SV and LV stroke subtypes. The distinct HLA associations with SV and LV stroke
      suggest that different pathologic processes may be involved in the development of
      stroke in children with SCA. If these results are confirmed in a larger study,
      HLA type may serve as a useful marker for the early identification of SCA
      patients at high risk for stroke.

PMID- 12517811
TI  - Src-family kinase signaling modulates the adhesion of Plasmodium falciparum on
      human microvascular endothelium under flow.
AB  - The pathogenicity of Plasmodium falciparum is due to the unique ability of
      infected erythrocytes (IRBCs) to adhere to vascular endothelium. We investigated
      whether adhesion of IRBCs to CD36, the major cytoadherence receptor on human
      dermal microvascular endothelial cells (HDMECs), induces intracellular signaling
      and regulates adhesion. A recombinant peptide corresponding to the minimal CD36
      binding domain from P falciparum erythrocyte membrane protein 1 (PfEMP1), as well
      as an anti-CD36 monoclonal antibody (mAb) that inhibits IRBC binding, activated
      the mitogen-activated protein (MAP) kinase pathway that was dependent on Src
      family kinase activity. Treatment of HDMECs with a Src-family kinase-selective
      inhibitor (PP1) inhibited adhesion of IRBCs in a flow-chamber assay by 72% (P
      <.001). More importantly, Src-family kinase activity was also required for
      cytoadherence to intact human microvessels in a human/severe combined
      immunodeficient (SCID) mouse model in vivo. The effect of PP1 could be mimicked
      by levamisole, a specific alkaline-phosphatase inhibitor. Firm adhesion to PP1
      treated endothelium was restored by exogenous alkaline phosphatase. In contrast,
      inhibition of the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 MAP
      kinase pathways had no immediate effect on IRBC adhesion. These results suggest a
      novel mechanism for the modulation of cytoadherence under flow conditions through
      a signaling pathway involving CD36, Src-family kinases, and an ectoalkaline
      phosphatase. Targeting endothelial ectoalkaline phosphatases and/or signaling
      molecules may constitute a novel therapeutic strategy against severe falciparum
      malaria.

PMID- 12517812
TI  - Functional and comparative analysis of globin loci in pufferfish and humans.
AB  - To further our understanding of the regulation of vertebrate globin loci, we have
      isolated cosmids containing alpha- and beta-globin genes from the pufferfish Fugu
      rubripes. By DNA fluorescence in situ hybridization (FISH) analysis, we show that
      Fugu contains 2 distinct hemoglobin loci situated on separate chromosomes. One
      locus contains only alpha-globin genes (alpha-locus), whereas the other also
      contains a beta-globin gene (alpha beta-locus). This is the first poikilothermic
      species analyzed in which the physical linkage of the alpha- and beta-globin
      genes has been uncoupled, supporting a model in which the separation of the alpha
      and beta-globin loci has occurred through duplication of a locus containing both
      types of genes. Surveys for transcription factor binding sites and DNaseI
      hypersensitive site mapping of the Fugu alpha beta-locus suggest that a strong
      distal locus control region regulating the activity of the globin genes, as found
      in mammalian beta-globin clusters, may not be present in the Fugu alpha beta
      locus. Searching the human and mouse genome databases with the genes surrounding
      the pufferfish hemoglobin loci reveals that homologues of some of these genes are
      proximal to cytoglobin, a recently described novel member of the globin family.
      This provides evidence that duplication of the globin loci has occurred several
      times during evolution, resulting in the 5 human globin loci known to date, each
      encoding proteins with specific functions in specific cell types.

PMID- 12517813
TI  - Impaired granulocytopoiesis in patients with chronic idiopathic neutropenia is
      associated with increased apoptosis of bone marrow myeloid progenitor cells.
AB  - To probe the pathophysiologic mechanisms underlying neutropenia in patients with
      chronic idiopathic neutropenia (CIN) with hypoplastic and left-shifted
      granulocytic series in the bone marrow (BM), we have studied granulocytopoiesis
      in 32 adults with CIN by evaluating the number and survival characteristics of
      cells in several stages of granulocyte differentiation using flow cytometry and
      BM culture assays. We found that patients with CIN displayed a low percentage of
      CD34(+)/CD33(+) cells, defective granulocyte colony-forming unit (CFU-G) growth
      potential of BM mononuclear or purified CD34(+) cells, and low CFU-G recovery in
      long-term BM cultures (LTBMCs), compared with controls (n = 46). A low percentage
      of CD34(+)/CD33(+) cells in patients was associated with accelerated apoptosis
      and Fas overexpression within this cell compartment compared with controls. No
      significant difference was documented in the percentage of apoptotic cells or the
      Fas(+) cells within the fractionated CD34(+)/CD33(-), CD34(-)/CD33(+), and CD34(
      )/CD33(-)/CD15(+) BM subpopulations or the peripheral blood neutrophils,
      suggesting that the underlying cellular defect in CIN probably concerns the
      committed granulocyte progenitors. LTBMC stromal layers from patients produced
      abnormally high amounts of tumor necrosis factor alpha and cytokine levels in
      culture supernatants inversely correlated with the number of myeloid progenitor
      cells and positively with the proportion of apoptotic CD34(+) cells. Patient
      LTBMC stromal layers displayed pathologic interferon gamma and Fas-ligand mRNA
      expression and failed to support normal myelopoiesis. These data suggest that
      impaired granulocytopoiesis in CIN is probably due to overproduction of
      inflammatory cytokines by immune cells within the BM microenvironment that may
      exert an inhibitory effect on myelopoiesis by inducing Fas-mediated apoptosis in
      the granulocyte progenitors.

PMID- 12517814
TI  - Paracrine interactions of basic fibroblast growth factor and interleukin-6 in
      multiple myeloma.
AB  - Myeloma cells express basic fibroblast growth factor (bFGF), an angiogenic
      cytokine triggering marrow neovascularization in multiple myeloma (MM). In solid
      tumors and some lymphohematopoietic malignancies, angiogenic cytokines have also
      been shown to stimulate tumor growth via paracrine pathways. Since interleukin-6
      (IL-6) is a potent growth and survival factor for myeloma cells, we have studied
      the effects of bFGF on IL-6 secretion by bone marrow stromal cells (BMSCs) and
      its potential reverse regulation in myeloma cells. Both myeloma-derived cell
      lines and myeloma cells isolated from the marrow of MM patients were shown to
      express and secrete bFGF. Cell-sorting studies identified myeloma cells as the
      predominant source of bFGF in MM marrow. BMSCs from MM patients and control
      subjects expressed high-affinity FGF receptors R1 through R4. Stimulation of
      BMSCs with bFGF induced a time- and dose-dependent increase in IL-6 secretion
      (median, 2-fold; P <.001), which was completely abrogated by anti-bFGF
      antibodies. Conversely, stimulation with IL-6 enhanced bFGF expression and
      secretion by myeloma cell lines (2-fold; P =.02) as well as MM patient cells (up
      to 3.6-fold; median, 1.5-fold; P =.002). This effect was inhibited by anti-IL-6
      antibody. When myeloma cells were cocultured with BMSCs in a noncontact transwell
      system, both IL-6 and bFGF concentrations in coculture supernatants increased 2-
      to 3-fold over the sum of basal concentrations in the monoculture controls. The
      IL-6 increase was again partially, but significantly, inhibited by anti-bFGF. The
      data demonstrate a paracrine interaction between myeloma and marrow stromal cells
      triggered by mutual stimulation of bFGF and IL-6.

PMID- 12517815
TI  - A phase 2 trial of combination low-dose thalidomide and prednisone for the
      treatment of myelofibrosis with myeloid metaplasia.
AB  - Single-agent thalidomide (THAL) at "conventional" doses (> 100 mg/d) has been
      evaluated in myelofibrosis with myeloid metaplasia (MMM) based on its
      antiangiogenic properties and the prominent neoangiogenesis that occurs in MMM.
      THAL monotherapy at such doses produces approximately a 20% response rate in
      anemia but is poorly tolerated (an adverse dropout rate of > 50% in 3 months). To
      improve efficacy and tolerability, we prospectively treated 21 symptomatic
      patients (hemoglobin level < 10 g/dL or symptomatic splenomegaly) with MMM with
      low-dose THAL (50 mg/d) along with a 3-month oral prednisone (PRED) taper
      (beginning at 0.5 mg/kg/d). THAL-PRED was well tolerated in all enrolled
      patients, with 20 patients (95%) able to complete 3 months of treatment. An
      objective clinical response was demonstrated in 13 (62%) patients, all
      improvements in anemia. Among 10 patients who were dependent on erythrocyte
      transfusions, 7 (70%) improved and 4 (40%) became transfusion independent. Among
      8 patients with thrombocytopenia (platelet count < 100 x 10(9)/L), 6 (75%)
      experienced a 50% or higher increase in their platelet count. In 4 of 21 patients
      (19%), spleen size decreased by more than 50%. Responses observed were mostly
      durable after discontinuation of the PRED. The dose of THAL in this study (50
      mg/d) was better tolerated than the higher doses used in previous studies.
      Adverse events associated with corticosteroid therapy were mild and transient.
      Clinical responses did not correlate with improvements in either intramedullary
      fibrosis or angiogenesis. THAL-PRED is well tolerated and preliminarily appears
      to be a promising drug regimen for treating cytopenias in patients with MMM.

PMID- 12517816
TI  - Genomically complex lymphomas undergo sustained tumor regression upon MYC
      inactivation unless they acquire novel chromosomal translocations.
AB  - The targeted inactivation of oncogenes may be a specific and effective treatment
      for cancer. However, because human cancers are the consequence of multiple
      genetic changes, the inactivation of one oncogene may not be sufficient to cause
      sustained tumor regression. Moreover, cancers are genomically unstable and may
      readily compensate for the inactivation of a single oncogene. Here we confirm by
      spectral karyotypic analysis that MYC-induced hematopoietic tumors are highly
      genetically complex and genomically unstable. Nevertheless, the inactivation of
      MYC alone was found to be sufficient to induce sustained tumor regression. After
      prolonged MYC inactivation, some tumors exhibited a distinct propensity to
      relapse. When tumors relapsed, they no longer required the overexpression of MYC
      but instead acquired novel chromosomal translocations. We conclude that even
      highly genetically complex cancers are reversible on the inactivation of MYC,
      unless they acquire novel genetic alterations that can sustain a neoplastic
      phenotype.

PMID- 12517817
TI  - High incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric MALT
      lymphoma.
AB  - In approximately 5% to 10% of gastric mucosa-associated lymphoid tissue (MALT)
      lymphomas, evidence of Helicobacter pylori infection is absent, and their
      pathogenesis is poorly understood. We reviewed the clinical data and histology,
      and we examined t(11;18)(q21;q21) and BCL10 expression pattern in 17 such cases.
      In each case, the absence of H pylori was confirmed by negative serology and
      histology/immunohistochemistry. Five cases with stage I(E) disease were first
      treated with antibiotics, and none of them showed any endoscopic or histologic
      response. Review of the histology failed to identify any apparent difference
      between gastric MALT lymphomas with and without H pylori infection. Reverse
      transcription-polymerase chain reaction (RT-PCR) showed t(11;18)(q21;q21) in 9
      (53%) of 17 cases, more frequent in lymphomas at stage II(E) or above (5 of 6)
      than those at stage I(E) (3 of 10). Two t(11;18)(q21;q21)-positive lymphomas were
      treated by partial gastrectomy and more than 16 years later showed lymphoma
      relapse in the gastric stump with dissemination to other mucosal sites, poorly
      responsive to therapy. BCL10 nuclear expression was observed in 7 of 8
      t(11;18)(q21;q21)-positive cases and 4 of 7 t(11;18)(q21;q21)-negative cases,
      including one case suspicious for a BCL10-involved chromosomal translocation. Our
      results show that t(11;18)(q21;q21) occurs at a high frequency in H pylori
      negative gastric MALT lymphomas. Translocation-positive gastric MALT lymphomas
      tend to be aggressive, and patients with such lymphomas might benefit from prompt
      treatment and close follow-up.

PMID- 12517818
TI  - Role of the hospital-based microbiology laboratory in preparation for and
      response to a bioterrorism event.

PMID- 12517819
TI  - Cell wall thickening is a common feature of vancomycin resistance in
      Staphylococcus aureus.
AB  - We have previously shown that a thickened cell wall is responsible for the
      vancomycin resistance of vancomycin-resistant Staphylococcus aureus (VRSA)
      (equivalent to vancomycin-intermediate S. aureus and glycopeptide-intermediate S.
      aureus) strain Mu50 (L. Cui, H. Murakami, K. Kuwahara-Arai, H. Hanaki, and K.
      Hiramatsu, Antimicrob. Agents Chemother. 44:2276-2285, 2000). However, the
      mechanism of vancomycin resistance in other VRSA strains remained unclear. In
      this study, 16 clinical VRSA strains from seven countries were subjected to
      serial daily passage in drug-free medium. After 10 to 84 days of passage in the
      nonselective medium, passage-derived strains with decreased MICs of vancomycin
      (MIC, <4 mg/liter) were obtained. However, all of the passage-derived strains
      except one (15 of 16) still possessed subpopulations that were resistant to
      vancomycin as judged by population analysis, and vancomycin-resistant mutant
      strains were selected from the passage-derived strains by one-step vancomycin
      selection with a frequency of 4.25 x 10(-6) to 1.64 x 10(-3). The data indicated
      that vancomycin-resistant cells are frequently generated from the passage-derived
      strains even after vancomycin selective pressure is lifted. Cell wall thicknesses
      and MICs of glycopeptides (vancomycin and teicoplanin) and beta-lactams (imipenem
      and oxacillin) were determined for a total of 48 strains, including 15 sets of
      three strains: the clinical VRSA strain, the passage-derived strain, and the
      vancomycin-resistant mutant strain obtained from the passage-derived strain. No
      simple correlation between glycopeptide and beta-lactam MICs was seen, while
      significant correlations between MICs of vancomycin and teicoplanin (r = 0.679; P
      < 0.001) and between MICs of imipenem and oxacillin (r = 0.787; P < 0.001) were
      recognized. Moreover, all of the VRSA strains had significantly thickened cell
      walls, which became thinner with the loss of vancomycin resistance during drug
      free passages and again became thick in the resistant mutant strains. The data
      showed that cell wall thickness had high correlation with the MICs of the two
      glycopeptides (correlation coefficients, 0.908 for vancomycin and 0.655 for
      teicoplanin) but not with those of the beta-lactam antibiotics tested. These
      results together with coupled changes of cell wall thickness and vancomycin MICs
      in 16 isogenic sets of strains indicate that thickening of the cell wall is a
      common phenotype of clinical VRSA strains and may be a phenotypic determinant for
      vancomycin resistance in S. aureus.

PMID- 12517821
TI  - Subtyping of Salmonella enterica serotype enteritidis strains by manual and
      automated PstI-SphI ribotyping.
AB  - Salmonella enterica subsp. enterica serotype Enteritidis is not readily subtyped
      beyond the level of phage type (PT). A recently developed method for ribotyping
      of this organism, which uses a mixture of PstI and SphI (PS) for restriction of
      DNA (PS ribotyping), has proved useful for further subtyping of a number of PTs
      of this organism, including PT 4. However, it has not been extensively tested
      with PT 8. In the present study the PS ribotyping method was used to investigate
      outbreaks of both S. enterica serotype Enteritidis PT 4 and PT 8 and provided
      subtyping data that were consistent with information obtained from epidemiologic
      investigations. The method proved to be more discriminatory than phage typing and
      pulsed-field gel electrophoresis (PFGE) combined and was useful for investigating
      a pseudo-outbreak involving isolates that had identical PTs and PFGE types but
      that could not be linked epidemiologically. Several PS ribotypes were found
      within the cluster of isolates indistinguishable by other subtyping methods,
      confirming the epidemiologic findings. Although the PS ribotyping method proved
      to have a superior discriminatory ability in resolving clusters, it did not have
      high enough throughput for use in outbreak investigations. This method has
      therefore been adapted for use in automated ribotyping with a RiboPrinter, and
      the results were compared with those obtained by manual ribotyping. Both methods
      produce equivalent results and are useful for obtaining epidemiologically
      relevant subtyping data for S. enterica serotype Enteritidis, including PT 8
      strains not extensively tested previously.

PMID- 12517820
TI  - Comparative genotyping of Campylobacter jejuni by amplified fragment length
      polymorphism, multilocus sequence typing, and short repeat sequencing: strain
      diversity, host range, and recombination.
AB  - Three molecular typing methods were used to study the relationships among 184
      Campylobacter strains isolated from humans, cattle, and chickens. All strains
      were genotyped by amplified fragment length polymorphism (AFLP) analysis,
      multilocus sequence typing (MLST), and sequence analysis of a genomic region with
      short tandem repeats designated clustered regularly interspaced short palindromic
      repeats (CRISPRs). MLST and AFLP analysis yielded more than 100 different
      profiles and patterns, respectively. These multiple-locus typing methods resulted
      in similar genetic clustering, indicating that both are useful in disclosing
      genetic relationships between Campylobacter jejuni isolates. Group separation
      analysis of the AFLP analysis and MLST data revealed an unexpected association
      between cattle and human strains, suggesting a common source of infection.
      Analysis of the polymorphic CRISPR region carrying short repeats allowed about
      two-thirds of the typeable strains to be distinguished, similar to AFLP analysis
      and MLST. The three methods proved to be equally powerful in identifying strains
      from outbreaks of human campylobacteriosis. Analysis of the MLST data showed that
      intra- and interspecies recombination occurs frequently and that the role of
      recombination in sequence variation is 50 times greater than that of mutation.
      Examination of strains cultured from cecum swabs revealed that individual
      chickens harbored multiple Campylobacter strain types and that some genotypes
      were found in more than one chicken. We conclude that typing of Campylobacter
      strains is useful for identification of outbreaks but is probably not useful for
      source tracing and global epidemiology because of carriage of strains of multiple
      types and an extremely high diversity of strains in animals.

PMID- 12517822
TI  - Characterization of members of the Legionellaceae family by automated ribotyping.
AB  - In order to implement a new and reliable method for characterizing different
      species of Legionella, a genetic fingerprinting study with an automated
      ribotyping system (RiboPrinter) was completed with members of this genus which
      were deposited at the American Type Culture Collection. The RiboPrinter examined
      the different patterns of EcoRI digestion fragments from the rRNA operons of 110
      strains, representing 48 of the 49 described Legionella species as well as 70
      serogroups of those species. Distinctive and consistent patterns were obtained
      for the type strains of the 48 species investigated. Legionella pneumophila
      subsp. fraseri and L. pneumophila subsp. pascullei each generated a specific
      pattern, whereas L. pneumophila subsp. pneumophila produced six different
      fingerprint patterns. No correlation seemed to exist between the ribotypes
      obtained and the 15 serotypes of L. pneumophila. For the other species, those
      with two known serogroups presented two distinctive patterns with the RiboPrinter
      with the exception of L. hackeliae and L. quinlivanii, which yielded only one
      pattern. We also encountered ribotypes for strains which were not identified to
      the species level. The ribotypes generated for these strains with the RiboPrinter
      did not match those generated for known type strains, suggesting the putative
      description of new serogroups or species. Although the automated system did not
      have sufficient discriminatory ability to serve as an epidemiological tool in a
      clinical setting, it appeared to be a powerful tool for general genomic analysis
      of the Legionella isolates (e.g., determination of new species) and assessment of
      the interrelationship among Legionella strains through the RiboPrinter database
      connection.

PMID- 12517823
TI  - Identification of Mycobacterium avium genotypes with distinctive traits by
      combination of IS1245-based restriction fragment length polymorphism and
      restriction analysis of hsp65.
AB  - One-hundred eight Mycobacterium avium isolates from pigs, humans, birds, and
      bovines were typed by the IS1245-based restriction fragment length polymorphism
      (RFLP) method and PCR-restriction enzyme analysis (PRA) of hsp65. Nine clusters
      of isolates showing more than 80% similarity in their RFLP profiles were
      detected. The largest cluster (cluster B) included 32 of 79 pig isolates (40.5%),
      3 of 25 human isolates (12%), and 1 of 2 bovine isolates, comprising 33% of all
      isolates. The second largest cluster (cluster A) included 18 pig isolates (22.8%)
      and 6 human isolates (24%). Six smaller clusters included six pig isolates
      (clusters C and D), four and two human isolates (clusters E and F, respectively),
      two pig isolates (cluster I), and two pig isolates plus one bovine isolate and
      the avian purified protein derivative strain (cluster H). Cluster G represented
      the "bird-type" profile and included the bird isolate in this series, one pig
      isolate, plus reference strain R13. PRA revealed four allelic variants. Seventy
      seven isolates were identified as M. avium PRA variant I, 24 were identified as
      M. avium PRA variant II, 6 were identified as M. avium PRA variant III, and 1 was
      identified as M. avium PRA variant IV. Except for three isolates from cluster B,
      each of the RFLP clusters was associated with a single PRA pattern. Isolates with
      unique (nonclustered) RFLP profiles were distributed between PRA variants I and
      II, and there was one unique isolate of PRA variant IV. These observations are
      consistent with divergent evolution within M. avium, resulting in the emergence
      of distinct lineages with particular competence to infect animals and humans.

PMID- 12517824
TI  - Discrimination of human pathogenic subspecies of Francisella tularensis by using
      restriction fragment length polymorphism.
AB  - We describe the use of two insertion sequence elements (ISFtu1 and ISFtu2) in
      Francisella tularensis to type strains by restriction fragment length
      polymorphism (RFLP). The RFLP profiles of 17 epidemiologically unrelated isolates
      were determined and compared. Our results showed that RFLP profiles can be used
      to assign F. tularensis strains into five main groups corresponding to strains of
      F. tularensis subsp. tularensis, F. tularensis strain ATCC 6223, strains of F.
      tularensis subsp. holarctica, strains of F. tularensis subsp. holarctica from
      Japan, and F. tularensis subsp. mediaasiatica. The results confirm the genetic
      identities of these subspecies and also support the suggestion that strains of F.
      tularensis subsp. holarctica from Japan should be considered members of a
      separate biovar. These findings should support future studies to determine the
      genetic differences between strains of F. tularensis at the whole-genome level.

PMID- 12517825
TI  - Duration of infection and proportion of pigs persistently infected with porcine
      reproductive and respiratory syndrome virus.
AB  - Understanding the dynamics of porcine reproductive and respiratory syndrome virus
      (PRRSV) persistence in individual pigs is essential to the development of
      successful control programs. The objectives of this study were to investigate the
      proportion of inoculated pigs that become persistently infected with PRRSV and
      the duration of their infection. Additionally, different diagnostic techniques
      that detect persistent infections were compared. Twenty-eight 35-day-old pigs
      were inoculated with PRRSV. Serum and tonsil biopsy samples were collected on
      days 0, 7, 14, and 28 and then approximately monthly thereafter until day 251
      postinoculation (p.i.). Tonsil, lymph node, and lung samples were collected
      following euthanasia on day 251 p.i. Virus was isolated from serum and tonsil
      biopsy samples that had been collected through days 28 and 56 p.i., respectively.
      Viral RNA was detected by reverse transcription (RT)-PCR in serum and tonsil
      biopsy samples that had been collected through day 251 p.i., although no serum
      samples collected from days 84 to 196 p.i. were positive and the presence of
      infectious PRRSV was not detected by swine bioassay of tissue samples collected
      at necropsy. The results confirmed that RT-PCR is more sensitive than virus
      isolation in identifying PRRSV-infected pigs. Six pigs that were persistently
      infected through days 225 or 251 p.i. remained seropositive throughout the study,
      although one pig had an enzyme-linked immunosorbent assay sample-to-positive
      ratio that was only slightly above the cutoff value of 0.40. Twenty of 28 tonsil
      biopsy samples collected on day 84 p.i. were positive by RT-PCR compared to only
      1 positive biopsy sample out of 28 collected on day 119 p.i. The study's results
      indicate that most pigs clear PRRSV within 3 to 4 months, but that some may
      remain persistently infected for several months.

PMID- 12517826
TI  - Evaluation of a PCR assay for detection of Streptococcus pneumoniae in
      respiratory and nonrespiratory samples from adults with community-acquired
      pneumonia.
AB  - Streptococcus pneumoniae is the most common cause of community-acquired
      pneumonia, but it is undoubtedly underdiagnosed. We used a nested PCR assay
      (targeting the pneumolysin gene) to detect S. pneumoniae DNA in multiple sample
      types from 474 adults with community-acquired pneumonia and 183 control patients
      who did not have pneumonia. Plasma or buffy coat samples were PCR positive in
      only 6 of the 21 patients with positive blood cultures for S. pneumoniae and in
      12 other patients (4 of whom had no other laboratory evidence of S. pneumoniae
      infection). Buffy coat samples from two control patients (neither having evidence
      of S. pneumoniae infection), but no control plasma samples, were PCR positive.
      Although pneumococcal antigen was detected in the urine from 120 of 420 (29%)
      patients, only 4 of 227 (2%) urine samples tested were PCR positive. Overall, 256
      of 318 (81%) patients had PCR-positive sputum samples, including 58 of 59 samples
      from which S. pneumoniae was cultured. Throat swab samples from 229 of 417 (55%)
      patients were PCR positive and, in those who produced sputum, 96% also had
      positive PCR results from sputum. Throat swabs from 73 of 126 (58%) control
      patients were also PCR positive. We conclude that the pneumolysin PCR assay adds
      little to existing diagnostic tests for S. pneumoniae and is unable to
      distinguish colonization from infection when respiratory samples are tested.

PMID- 12517827
TI  - Deciphering an outbreak of drug-resistant Mycobacterium tuberculosis.
AB  - There have been ample warnings that multidrug-resistant (MDR) tuberculosis (TB)
      will continue to emerge if countries do not strengthen their control of TB. In
      low-incidence European countries, however, these warnings have been substantiated
      mainly by outbreaks in association with human immunodeficiency virus (HIV)
      positive patients. The aim of this study was to investigate an outbreak of
      infection with MDR and drug-resistant Mycobacterium tuberculosis that was
      diagnosed among 20 HIV-negative patients living in Norway. Of these, 19 were
      immigrants from East Africa and one was an ethnic Norwegian. We wanted to find
      out if transmission had taken place in Norway or abroad and to identify the
      genetic basis of drug resistance. The strains were analyzed by IS6110 restriction
      fragment length polymorphism, antibiotic susceptibility tests, spoligotyping,
      reverse hybridization to regions of the rpoB gene, and sequencing of the katG
      gene. Epidemiological links between the patients were mapped, and the strains
      were compared to those isolated in 36 other countries and regions. All strains
      were resistant to isoniazid and carried Ala234Gly, Ser315Thr, and Arg463Leu
      substitutions in the katG gene. Eleven strains were MDR and carried a Ser531Leu
      substitution in the rpoB gene. MDR was acquired in the index patient after
      arrival in Norway. Links were found among 14 patients. The strain was imported
      from Somalia but acquired MDR and was transmitted in Norway. This demonstrated
      that MDR strains are not necessarily imported from high-incidence countries and
      can be highly communicable. The outbreak underscores a deficiency in the TB
      control measures employed in many countries and challenges the adequacy of the
      policy of screening immigrants for TB only on arrival.

PMID- 12517828
TI  - Serotyping of 467 Cryptococcus neoformans isolates from clinical and
      environmental sources in Brazil: analysis of host and regional patterns.
AB  - Cryptococcus neoformans is an important zoopathogen, and it is one of the most
      prevalent lethal mycotic agents. Its polysaccharide capsule, synthesized in vivo
      and in vitro, is a virulence factor, contains predominantly glucuronoxylomannan,
      and is responsible for the antigenic differentiation of serotypes A, B, C, D, and
      AD. A total of 467 isolates of C. neoformans obtained from clinical and
      environmental sources from Brazilian regions were studied serologically by using
      the Crypto Check Iatron RM 304-K kit. Serotyping of the clinical isolates showed
      the following prevalences of the serotypes: A (77.95%), followed by B (18.2%), AD
      (1.3%), D (0.4%), C (0.2%), and untypeable (1.93%). The epidemiology of serotype
      A in the Brazilian southern and southeastern regions reproduces the picture
      observed worldwide. In contrast, serotype B was the most frequent agent of
      cryptococcosis in the northeastern region, occurring nearly equally in male and
      female healthy hosts. Among the isolates from environmental sources, serotypes A
      and B were found to occur in the hollows of tropical trees of the genera Cassia,
      Ficus, and MOQUILLEA: The few isolates from Eucalyptus camaldulensis debris were
      serotypes A and B and untypeable. Overall, no association with a specific host
      tree was identified for these serotypes, denoting a distinct ecoepidemiological
      regional pattern. The one serotype C isolate was recovered from a human
      immunodeficiency virus-negative host. Serotype AD predominated over serotype D
      among both clinical and environmental isolates.

PMID- 12517830
TI  - Regional distribution of antibodies to herpes simplex virus type 1 (HSV-1) and
      HSV-2 in men and women in Ontario, Canada.
AB  - This study estimated the regional and age- and gender-specific seroprevalences of
      herpes simplex virus type 1 (HSV-1) and HSV-2 in Ontario, Canada. Stored serum
      specimens from subjects aged 15 to 44 years, including men (n = 979), women not
      under prenatal care (n = 638), and women under prenatal care (n = 701) submitted
      for routine viral serology were randomly selected according to regional
      population size from public health laboratories. HSV-1 and HSV-2 testing was done
      with the MRL enzyme immunoassay (EIA) (Focus Technologies), and HSV-2 was also
      tested by the Gull/Meridian EIA. Specimens discordant for HSV-2 antibodies
      between the two EIAs were resolved by a recombinant immunoblot assay (Focus
      Technologies). The overall age- and gender-standardized seroprevalences of HSV-1
      and HSV-2 were 51.1% (95% confidence interval [CI], 50.1 to 52.1) and 9.1% (95%
      CI, 8.6 to 9.7), respectively. The seroprevalence of HSV-1 antibodies increased
      from 26.9 to 54.7% in men between 15 to 16 and 40 to 44 years of age, from 32.0
      to 88.7% in women not under prenatal care, and from 55.2 to 69.2% in women under
      prenatal care. The seroprevalence of HSV-2 increased from 3.8 to 21.3% in men
      between 15 to 16 and 40 to 44 years of age, from 0 to 18.9% in women not under
      prenatal care, and from 3.4 to 23.1% in women under prenatal care. HSV-2 results
      were discordant for 3.3% (76 of 2,318) of specimens. Both types of HSV antibodies
      appeared to be acquired earlier among women under prenatal care than among men
      and women not under prenatal care. Antibodies were more prevalent among people in
      northern Ontario (72.9% of subjects [range, 68.4 to 77.4%] for HSV-1 and 13.7% of
      subjects [95% CI, 10.2 to 17.2%] for HSV-2) than elsewhere.

PMID- 12517829
TI  - In vitro activities of voriconazole, posaconazole, and four licensed systemic
      antifungal agents against Candida species infrequently isolated from blood.
AB  - We determined the in vitro susceptibilities of 314 strains of Candida spp.,
      representing 13 species rarely isolated from blood, to posaconazole and
      voriconazole as well as four licensed systemic antifungal agents (amphotericin B,
      flucytosine, fluconazole, and itraconazole). The organisms included 153 isolates
      of C. krusei, 67 isolates of C. lusitaniae, 48 isolates of C. guilliermondii, 10
      isolates of C. famata, 10 isolates of C. kefyr, 6 isolates of C. pelliculosa, 5
      isolates of C. rugosa, 4 isolates of C. lipolytica, 3 isolates of C.
      dubliniensis, 3 isolates of C. inconspicua, 2 isolates of C. sake, and 1 isolate
      each of C. lambica, C. norvegensis, and C. zeylanoides. MIC determinations were
      made by the National Committee for Clinical Laboratory Standards reference broth
      microdilution method and Etest (amphotericin B). Resistance to both amphotericin
      B and fluconazole was observed in strains of C. krusei, C. lusitaniae, C.
      guilliermondii, C. inconspicua, and C. sake. Resistance to amphotericin B, but
      not to fluconazole, was also observed among isolates of C. kefyr and C. rugosa.
      Posaconazole and voriconazole were active (MIC, < or = 1 micro g/ml) against 94
      to 100% of these isolates. In contrast to the more common species of Candida
      causing bloodstream infection, these rare species appear to be less susceptible
      to the currently licensed systemic antifungal agents, with the exception of
      voriconazole. Continued surveillance will be necessary to detect the emergence of
      these species as more prevalent, resistant pathogens. The new triazoles appear to
      offer acceptable coverage of uncommon Candida sp. bloodstream infections.

PMID- 12517831
TI  - Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput
      SNP assays and association with Candida carriage in type I diabetics and
      nondiabetic controls.
AB  - beta-Defensins are cationic antimicrobial peptides expressed in epithelia. They
      exhibit antibacterial, antifungal, and antiviral properties. Defensins are a
      component of the innate immune response, and it has been proposed that they have
      a protective role in the oral cavity. Previous studies have shown that human beta
      defensin 1 (hBD-1) is constitutively expressed in oral epithelial cells but that
      expression varies between individuals. We tested the hypothesis that genetic
      variations in defensin peptide expression may be associated with opportunistic
      infections. This may be critical in the immunocompromised patient population, in
      which innate immune responses may have a relatively more important role. Oral
      Candida carriage status and the presence of six single-nucleotide polymorphisms
      (SNPs) in the DEFB1 gene encoding hBD-1 were evaluated in type I diabetic
      patients (n = 43) and nondiabetic controls (n = 50). Genomic DNA was obtained
      from buccal swabs. Portions of the DEFB1 gene were amplified, and each SNP was
      analyzed by a TaqMan assay, standardized with control DNA of known genotype.
      Candida carriage status was determined from unstimulated saliva on CHROMagar
      plating medium. A low level of Candida carriage was defined as < or = 350 CFU/ml.
      A high level of Candida carriage was seen in 44% of the diabetic subjects but
      only in 28% of the nondiabetic controls (P < 0.05). C. albicans predominated;
      however, diabetic subjects, especially those with high levels of carriage, showed
      an increased proportion of Candida glabrata and C. tropicalis. There was a strong
      association between an SNP in the 5' untranslated region (C-->G at position -44)
      and Candida carriage in both groups. Among individuals in the diabetic population
      who had the SNP allele 2 (G), 58% had low CFU, while 6% had high CFU. The C-->G
      SNP at position -44 is associated with low levels of Candida carriage. The
      resultant odd ratios are statistically significant for a protective effect (odd
      ratios, 25 for diabetic subjects and 8.5 for nondiabetic subjects). These results
      indicate that genetic variations in the DEFB1 gene encoding hBD-1 may have a
      major role in mediating and/or contributing to susceptibility to oral infection.

PMID- 12517832
TI  - Evaluation of Etest method for determining voriconazole and amphotericin B MICs
      for 162 clinical isolates of Cryptococcus neoformans.
AB  - The performance of the Etest for voriconazole and amphotericin B susceptibility
      testing of 162 isolates of Cryptococcus neoformans was assessed against the
      National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution
      method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read
      after incubation for 72 h at 35 degrees C. MICs were determined by Etest for all
      162 isolates with RPMI 1640 agar containing 2% glucose (RPG agar) and were read
      after incubation for 72 h at 35 degrees C. The Etest results for both
      voriconazole and amphotericin B correlated well with reference MICs. Agreement
      was 94% for voriconazole and 99% for amphotericin B. When discrepancy was noted
      between the results obtained by Etest and broth microdilution for voriconazole,
      the Etest generally provided a higher MIC. The Etest method using RPG agar
      appears to be a useful method for determining the susceptibility of C. neoformans
      to voriconazole and amphotericin B.

PMID- 12517834
TI  - Identification of catalase-negative, non-beta-hemolytic, gram-positive cocci
      isolated from milk samples.
AB  - This study was undertaken in an effort to improve the identification scheme of
      catalase-negative, non-beta-hemolytic, gram-positive cocci isolated from milk
      samples obtained from cows. First, the sensitivity and specificity of the
      identification procedure currently in use in our laboratory were compared to the
      results obtained with API 20 STREP strips which were set as the gold standard.
      Second, a number of other identification tests, which could contribute to
      increase the sensitivity and specificity of the identification procedure of these
      microorganisms, were evaluated and selected. The data have shown that there is a
      necessity to review the identification procedure. Some modifications are
      suggested to laboratories doing milk sample analyses. A standardized procedure,
      using the CAMP test, esculin and sodium hippurate hydrolysis, the presence of the
      enzymes pyrolidonyl arylaminase and leucine aminopeptidase, and acid production
      from 1% inulin and raffinose broth, would not only improve the results of the
      identification process of gram-positive cocci isolated from milk samples but also
      ensure greater uniformity of the epidemiological data.

PMID- 12517833
TI  - Molecular assays for detection of human metapneumovirus.
AB  - The recent description of the respiratory pathogen human metapneumovirus (hMPV)
      has highlighted a deficiency in current diagnostic techniques for viral agents
      associated with acute lower respiratory tract infections. We describe two novel
      approaches to the detection of viral RNA by use of reverse transcriptase PCR (RT
      PCR). The PCR products were identified after capture onto a solid-phase medium by
      hybridization with a sequence-specific, biotinylated oligonucleotide probe. The
      assay was applied to the screening of 329 nasopharyngeal aspirates sampled from
      patients suffering from respiratory tract disease. These samples were negative
      for other common microbial causes of respiratory tract disease. We were able to
      detect hMPV sequences in 32 (9.7%) samples collected from Australian patients
      during 2001. To further reduce result turnaround times we designed a fluorogenic
      TaqMan oligoprobe and combined it with the existing primers for use on the
      LightCycler platform. The real-time RT-PCR proved to be highly reproducible and
      detected hMPV in an additional 6 out of 62 samples (9.6%) tested during the
      comparison of the two diagnostic approaches. We found the real-time RT-PCR to be
      the test of choice for future investigation of samples for hMPV due to its speed,
      reproducibility, specificity, and sensitivity.

PMID- 12517835
TI  - Phenotypic and genotypic characterization of provisional serotype Shigella
      flexneri 1c and clonal relationships with 1a and 1b strains isolated in
      Bangladesh.
AB  - The serotypes of 144 strains of Shigella flexneri serotype 1 (serotypes 1a, 1b,
      and 1c) isolated from patients attending the Dhaka treatment center of the
      International Centre for Diarrhoeal Disease Research, Bangladesh, between 1997
      and 2001 were serologically confirmed by using commercially available antisera
      and a panel of monoclonal antibodies specific for S. flexneri group and type
      factor antigen (MASF). Among serotype 1 isolates, the prevalence of provisional
      serotype S. flexneri 1c increased from 0 to 56% from 1978 to 2001 in Bangladesh.
      Detailed biochemical studies revealed that none of the strains of serotype 1
      produced indole, while all the strains fermented mannose, mannitol, and
      trehalose. Twenty percent of the serotype 1c and all the serotype 1a strains
      fermented maltose and 53% of the serotype 1c strains and 60% of the serotype 1a
      strains fermented arabinose, whereas all serotype 1b strains were negative for
      fermentation of these sugars. Only 18% of serotype 1b strains were resistant to
      nalidixic acid, and most of the serotype 1c and 1b strains were resistant to
      ampicillin, tetracycline, and trimethoprim-sulfamethoxazole. All the strains of
      serotypes 1a and 1b and about 88% of the serotype 1c strains were found to be
      invasive by the Sereny test, had a 140-MDa plasmid, and had Congo red absorption
      ability. Plasmid profile analysis showed that 26% of the strains of serotype 1
      contained identical patterns. Most of the serotype 1c strains (72%) had the 1.6
      MDa plasmid, which was not found in either serotype 1a or 1b strains. A self
      transmissible middle-range plasmid (35 to 80 MDa) was found in some strains
      carrying the multiple-antibiotic-resistance gene. Pulsed-field gel
      electrophoresis analysis yielded three types (types A, B, and C) with numerous
      subtypes among the serotype 1c strains, whereas serotypes 1b and 1a yielded only
      one type for each serotype, and those types were related to the types for
      serotype 1c strains. Ribotyping analysis yielded three patterns for serotype 1c
      strains and one pattern each for serotype 1a and 1b strains which were similar to
      the patterns for the serotype 1c strains. Overall analysis of the results
      concluded that subserotype 1c is closely related to serotypes 1a and 1b.
      Furthermore, the high rate of prevalence of serotype 1c necessitates the
      commercial production of antibody against this subserotype to allow the
      determination of the actual burden of shigellosis caused by provisional serotype
      1c.

PMID- 12517836
TI  - Bloodstream infection in neutropenic cancer patients related to short-term
      nontunnelled catheters determined by quantitative blood cultures, differential
      time to positivity, and molecular epidemiological typing with pulsed-field gel
      electrophoresis.
AB  - To determine the rate of catheter-related bloodstream infection (CRBSI) among
      cases of primary bloodstream infection (BSI) in febrile neutropenic cancer
      patients with short-term nontunnelled catheters, quantitative paired blood
      cultures (Isolator) from the central venous catheter (CVC) and peripheral vein
      were obtained between November 1999 and January 2001. Bactec blood culture
      bottles were obtained to determine the differential time to positivity (DTP).
      CRBSI was defined as a quantitative blood culture ratio of >5:1 (CVC versus
      peripheral) with proven identity of isolates from positive peripheral and CVC
      blood cultures as confirmed by pulsed-field gel electrophoresis. Forty-nine
      episodes of primary BSI were detected among 235 cancer patients with febrile
      neutropenia. Of these, 18 episodes (37%) were CRBSI and 31 (63%) were BSI with an
      unknown portal of entry. Coagulase-negative staphylococci were present in nine
      cases of CRBSI (50%). The identity of isolates from peripheral and CVC blood
      cultures was confirmed in all cases. Earlier positivity (>2 h) of CVC-drawn
      versus peripheral blood cultures was observed in 18 of 22 CRBSI-associated blood
      cultures (sensitivity, 82%; specificity, 88%; positive predictive value, 75%;
      negative predictive value, 92%). In summary, CRBSI accounted for 37% of cases of
      primary BSI in this population of neutropenic cancer patients. DTP compares
      favourably with quantitative blood cultures for the diagnosis of CRBSI and may be
      particularly useful for patients in whom catheter salvage is highly desirable.

PMID- 12517837
TI  - Genetic diversity of Vibrio cholerae O1 in Argentina and emergence of a new
      variant.
AB  - The genetic diversity of Vibrio cholerae O1 strains from Argentina was estimated
      by random amplified polymorphic DNA (RAPD) analysis and pulsed-field gel
      electrophoresis (PFGE). Twenty-nine isolates carrying the virulence genes ctxA,
      zot, ace, and tcpA appeared to represent a single clone by both typing methods;
      while 11 strains lacking these virulence genes exhibited several heterogeneous
      RAPD and PFGE patterns. Among the last group, a set of isolates from the province
      Tucuman showed a single RAPD pattern and four closely related PFGE profiles.
      These strains, isolated from patients with diarrhea, did not produce the major V.
      cholerae O1 virulence determinants, yet cell supernatants of these isolates
      caused a heat-labile cytotoxic effect on Vero and Y-1 cells and elicited
      significant variations on the water flux and short-circuit current in human small
      intestine mounted in an Ussing chamber. All these effects were completely
      abolished by incubation with a specific antiserum against El Tor hemolysin,
      suggesting that this virulence factor was responsible for the toxic activity on
      both the epithelial cells and the small intestine specimens and may hence be
      involved in the development of diarrhea. We propose "Tucuman variant" as the
      designation for this new cluster of cholera toxin-negative V. cholerae O1
      strains.

PMID- 12517838
TI  - Evaluation of two new automated assays for hepatitis B virus surface antigen
      (HBsAg) detection: IMMULITE HBsAg and IMMULITE 2000 HBsAg.
AB  - In recent years the diagnostic industry has developed new automated immunoassays
      for the qualitative detection of hepatitis B virus (HBV) surface antigen (HBsAg)
      in serum and plasma samples that are performed on analyzers that permit a high
      speed throughput, random access, and primary tube sampling. The aim of the
      present study was the evaluation of two new automated HBsAg screening assays,
      IMMULITE HBsAg and IMMULITE 2000 HBsAg, from Diagnostic Products Corporation. The
      new HBsAg assays were compared to well-established tests (Auszyme Monoclonal
      [overnight incubation, version B], IMx HBsAg, AxSYM HBsAg, and Prism HBsAg [all
      from Abbott] and Elecsys HBsAg [Roche Diagnostics]). In the evaluation were
      included seroconversion panels, sera from the acute and chronic phases of
      infection, dilution series of various HBsAg standards, HBV subtypes and S gene
      mutants. To challenge the specificity of the new assays, sera from HBsAg-negative
      blood donors, pregnant women, and dialysis and hospitalized patients and
      potentially cross-reactive samples were investigated. IMMULITE HBsAg and IMMULITE
      2000 HBsAg, although not as sensitive as the Elecsys HBsAg assay, were equivalent
      to the AxSYM HBsAg assay and showed a higher sensitivity than the Auszyme
      Monoclonal B and IMx HBsAg systems for detection of acute infection in
      seroconversion panels. The specificities (100%) of both IMMULITE assays on
      unselected blood donors and potentially interfering samples were comparable to
      those of the alternative assays after repeated testing. In conclusion, the new
      IMMULITE HBsAg and IMMULITE 2000 HBsAg assays show a good sensitivity for HBsAg
      detection compared to other well-established tests. The specificity on repeatedly
      tested samples was equivalent to that of the alternative assays. The rapid
      turnaround time, primary tube sampling, and on-board dilution make it an
      interesting assay system for clinical laboratory diagnosis.

PMID- 12517839
TI  - Development and evaluation of a PCR-enzyme-linked immunosorbent assay for
      diagnosis of human brucellosis.
AB  - In order to overcome some of the limitations of conventional microbiological
      techniques in the diagnosis of human brucellosis, a simple PCR-enzyme-linked
      immunosorbent assay (PCR-ELISA) was developed. After amplification of a 223-bp
      sequence of a gene that codes for the synthesis of an immunogenetic membrane
      protein specific for the Brucella genus (BCSP31), the digoxigenin-labeled
      amplified product was hybridized with a biotinylated capture probe which was
      complementary to the inner part of the amplicon. The hybrid was captured on
      streptavidin-coated microtiter plates and detected by using an antidigoxigenin
      Fab-peroxidase conjugate. The detection limit of the PCR-ELISA in a background of
      3.5 micro g of human genomic DNA was 10 fg (two bacterial cells). The PCR-ELISA
      showed an analytical sensitivity higher than that of ethidium bromide staining
      and equal to that obtained by conventional PCR followed by dot blot
      hybridization. In 59 peripheral blood samples from 57 consecutive patients with
      active brucellosis and 113 control samples, the PCR-ELISA was found to be 94.9%
      sensitive and 96.5% specific, whereas the sensitivity of the blood culture was
      only 70.1%. Since the assay can be performed in 1 day, is very reproducible, is
      easily standardized, and avoids the risk of infection in laboratory workers, this
      PCR-ELISA seems to be a practical and reliable tool for the diagnosis of human
      brucellosis.

PMID- 12517840
TI  - Simultaneous detection, subgrouping, and quantitation of respiratory syncytial
      virus A and B by real-time PCR.
AB  - Timely diagnosis of respiratory syncytial virus (RSV) infection is critical for
      appropriate treatment of lower respiratory infection in young children. To
      facilitate diagnosis, we developed a rapid, specific, and sensitive TaqMan PCR
      method for detection of RSV A and RSV B. Two sets of primer-probe pairs were
      selected from the nucleotide sequences encoding the nucleocapsid protein--one
      targeting RSV A and the other targeting RSV B. The specificity of the TaqMan
      reverse transcription-PCR assay was evaluated by testing each primer-probe pair
      against various viruses derived from laboratory virus stocks, as well as clinical
      respiratory specimens. Fluorescent signals were observed only in the presence of
      RSV A and/or RSV B. The sensitivity of our quantitative PCR assay was determined
      on the basis of PFU and virus particle counts. The resulting assay sensitivity
      was found to be 0.023 PFU, or two copies of viral RNA, for RSV A and 0.018 PFU,
      or nine copies of viral RNA, for RSV B. This quantitative TaqMan PCR assay was
      utilized to diagnose 175 nasopharyngeal aspirates obtained from children in Hong
      Kong with respiratory symptoms during the winter of 2000 and 2001. Among these
      specimens, TaqMan PCR detected 36 RSV-positive samples, 10 of which were
      identified as RSV A and 26 of which were identified as RSV B, whereas culture
      confirmation identified 21 RSV-positive specimens and immunofluorescence
      identified 32 RSV-positive specimens, all of which were among those identified by
      PCR. The results confirmed the accuracy of our TaqMan PCR assay and demonstrated
      its improved sensitivity versus classical methods.

PMID- 12517841
TI  - Occurrence and phenotypic characteristics of extended-spectrum beta-lactamases
      among members of the family Enterobacteriaceae at the Tel-Aviv Medical Center
      (Israel) and evaluation of diagnostic tests.
AB  - We assessed the prevalence and phenotypic characteristics of extended-spectrum
      beta-lactamase (ESBL) producers among cefuroxime-resistant (CXM-R) (MIC > or = 32
      micro g/ml) members of the family Enterobacteriaceae in our institution. The 438
      CXM-R clinical isolates obtained from nonurine sources among inpatients were
      screened. ESBL production was confirmed by disk diffusion assay using cefpodoxime
      (CPD), cefotaxime (CTX), and ceftazidime (CTZ) with and without clavulanate
      (CLAV). A difference of > or =5 mm in the size of the zone of inhibition in the
      presence of CLAV for at least one of the agents was considered representative of
      the ESBL phenotype: 186 isolates (42.5%) were confirmed as ESBL producers. The
      isolates tested and the rates of ESBL producers were as follows: Klebsiella spp.
      (n = 81), 79%; Proteus spp. (n = 58), 62%; Escherichia coli (n = 64), 53%;
      Enterobacter spp. (n = 69), 42%; Serratia spp. (n = 70), 14%; Citrobacter spp. (n
      = 25), 24%; Providencia spp. (n = 21), 24%; Morganella spp. (n = 41), 5%; and
      Kluyvera (n = 3), 0%. The overall sensitivity of isolated ESBL confirmatory tests
      was 79% for CPD-CLAV, 66% for CTZ-CLAV, and 91% for CTX-CLAV. Sensitivities of
      CTZ-CLAV confirmatory tests for Klebsiella spp., Proteus spp., E. coli, and
      Enterobacter spp. were 84, 22, 76, and 62%, respectively, and those for CTX-CLAV
      were 95, 97, 94, and 83%, respectively. They were 90% for CPD-CLAV and CTZ-CLAV,
      95% for CPD-CLAV and CTX-CLAV, and 100% for CTZ-CLAV and CTX-CLAV. ESBL
      production was highly prevalent among Enterobacteriaceae. Using resistance to CXM
      as an ESBL screening criterion is a suitable option in high-incidence areas where
      Klebsiella spp. are not the dominant ESBL producers. This screening criterion may
      simplify the screening test and improve its sensitivity, although at the price of
      testing more isolates. The CTX-CLAV combination confirmed ESBL producers better
      than the CTZ-CLAV combination, with sensitivity varying between species. Combined
      CTZ-CLAV and CTX-CLAV testing detected all these strains; CPD-CLAV provided no
      additional benefit.

PMID- 12517842
TI  - Frequent recovery of a single clonal type of multidrug-resistant Staphylococcus
      aureus from patients in two hospitals in Taiwan and China.
AB  - One hundred thirty-two methicillin-resistant Staphylococcus aureus (MRSA)
      isolates recovered from patients with S. aureus infections between January 1998
      and February 1999 in two hospitals, one located in Taipei, Taiwan, and another in
      Nanjing, People's Republic of China, were examined for antibiotic susceptibility
      and for clonal type by a combination of three methods: hybridization of ClaI
      restriction digests with mecA- and Tn554-specific DNA probes and pulsed-field gel
      electrophoresis of chromosomal SmaI digests. Selected isolates representing each
      clonal type were also analyzed by spaA typing, multilocus sequence typing, and a
      multiplex PCR method capable of identifying the structural type of the
      staphylococcal cassette chromosome mec (SCCmec) carried by the bacteria. The
      overwhelming majority of isolates (126 of 132 or 95%) belonged to minor variants
      of a single clonal type resembling the Brazilian and Hungarian epidemic MRSA
      clones, which showed a common spaA type and which were either sequence type 239
      (ST239) or ST241 (a single-locus variant of ST239) in association with SCCmec
      type III or IIIA.

PMID- 12517843
TI  - Multicenter evaluation of the performance characteristics of the NucliSens HIV-1
      QT assay used for quantitation of human immunodeficiency virus type 1 RNA.
AB  - The analytical performance of the NucliSens HIV-1 QT assay, a highly sensitive
      test based on nucleic acid sequence-based amplification technology, was evaluated
      in a multicenter trial. Assay specificity was evaluated with 502 plasma (EDTA)
      specimens from human immunodeficiency virus type 1 (HIV-1)-seronegative volunteer
      donors. No HIV-1 RNA was reported in any of the donor specimens. Analytical
      sensitivity and reproducibility were estimated with panels prepared from a high
      titer well-characterized HIV-1 RNA stock (5.84 x 10(8) RNA copies/ml). The
      assay's dynamic range was linear from 10(6) to 10(1) HIV-1 RNA copies, with a
      lower detectable limit of 25 copies/ml and a 95% detection rate of 176 copies/ml.
      Sensitivity of the assay to detect HIV-1 RNA in clinical specimens from patients
      (n = 101) and in commercially available or prepared panels (n = 24) was compared
      with NASBA HIV-1 RNA QT (an earlier version of NucliSens HIV-1 QT) and with the
      Food and Drug Administration-approved standard and ultrasensitive AMPLICOR HIV-1
      MONITOR, version 1.0, assays. Detection of HIV-1 RNA was reproducible over a 5
      log range (mean standard deviation = 0.15 log). The NucliSens and the standard
      AMPLICOR assays were equivalent in detection of HIV-1 RNA (concentration, 10(3)
      to 10(5) copies/ml) in 57 clinical specimens. The NucliSens assay was more
      sensitive in detecting HIV-1 RNA at lower concentrations (</=10(2) copies/ml) (44
      of 44) than either the standard AMPLICOR test (12 of 19) or the NASBA assay (10
      of 25). A 25% increase in HIV-1 RNA detection frequency with panels was observed
      with the NucliSens assay (23 of 24) compared with the standard AMPLICOR test (17
      of 24). The new assay was highly specific and demonstrated good sensitivity with
      a broad linear dynamic range.

PMID- 12517844
TI  - Detection, isolation, and molecular subtyping of Escherichia coli O157:H7 and
      Campylobacter jejuni associated with a large waterborne outbreak.
AB  - The largest reported outbreak of waterborne Escherichia coli O157:H7 in the
      United States occurred in upstate New York following a county fair in August
      1999. Culture methods were used to isolate E. coli O157:H7 from specimens from
      128 of 775 patients with suspected infections. Campylobacter jejuni was also
      isolated from stools of 44 persons who developed diarrheal illness after
      attending this fair. There was one case of a confirmed coinfection with E. coli
      O157:H7 and C. jejuni. Molecular detection of stx(1) and stx(2) Shiga toxin
      genes, immunomagnetic separation (IMS), and selective culture enrichment were
      utilized to detect and isolate E. coli O157:H7 from an unchlorinated well and its
      distribution points, a dry well, and a nearby septic tank. PCR for stx(1) and
      stx(2) was shown to provide a useful screen for toxin-producing E. coli O157:H7,
      and IMS subculture improved recovery. Pulsed-field gel electrophoresis (PFGE) was
      used to compare patient and environmental E. coli O157:H7 isolates. Among patient
      isolates, 117 of 128 (91.5%) were type 1 or 1a (three or fewer bands different).
      Among the water distribution system isolates, 13 of 19 (68%) were type 1 or 1a.
      Additionally, PFGE of C. jejuni isolates revealed that 29 of 35 (83%) had
      indistinguishable PFGE patterns. The PFGE results implicated the water
      distribution system as the main source of the E. coli O157:H7 outbreak. This
      investigation demonstrates the potential for outbreaks involving more than one
      pathogen and the importance of analyzing isolates from multiple patients and
      environmental samples to develop a better understanding of bacterial transmission
      during an outbreak.

PMID- 12517845
TI  - Pneumocystis jiroveci internal transcribed spacer types in patients colonized by
      the fungus and in patients with pneumocystosis from the same French geographic
      region.
AB  - Pneumocystis jiroveci (human-derived Pneumocystis) infections can display a broad
      spectrum of clinical presentations, of which pulmonary colonization with the
      fungus may represent an important part, occurring frequently in patients with
      various underlying diseases and presenting alternative diagnoses of acute
      pneumocystosis (Pneumocystis carinii pneumonia [PCP]). There are few data
      concerning the P. jiroveci genotypes involved in pulmonary colonization, whereas
      several genotypes responsible for PCP in immunocompromised patients have been
      described. In this study, P. jiroveci genotypes have retrospectively been
      investigated and compared in 6 colonized patients and in 11 patients with PCP who
      were in the same hospital. Seventeen archival bronchoalveolar lavage samples were
      genotyped at internal-transcribed spacer 1 (ITS1) and ITS2 of the nuclear rRNA
      operon. Fourteen different genotypes were identified, of which 1 was found only
      in colonized patients, 10 were found only in patients with PCP, and 3 were found
      in both patient populations. Mixed infections were diagnosed in 2 of the 6
      colonized patients and in 6 of the 11 patients with PCP. The results show that
      similar genotypes can be responsible for PCP as well as pulmonary colonization.
      There is a high diversity of genotypes in colonized patients and in patients with
      PCP. Mixed infections may occur in these two patient populations. These shared
      features of P. jiroveci ITS genotypes in colonized patients and patients with PCP
      suggest that human populations infected by P. jiroveci, whatever the clinical
      manifestation, may play a role as a common reservoir for the fungus.

PMID- 12517846
TI  - Measurement of human cytomegalovirus loads by quantitative real-time PCR for
      monitoring clinical intervention in transplant recipients.
AB  - Quantitative monitoring of human cytomegalovirus (HCMV) infection is helpful in
      determining appropriate antiviral management of transplant recipients.
      Quantitative PCR technologies have demonstrated accuracy in measuring systemic
      HCMV loads. A total of 298 consecutive whole-blood specimens submitted to the
      Clinical Virology Laboratory at Vanderbilt University Medical Center from 15
      February to 31 October 1999 were included in the study. In addition to a
      qualitative colorimetric microtiter plate PCR assay (MTP-PCR) and a
      semiquantitative pp65 antigenemia assay, each specimen was measured for HCMV
      loads by a quantitative PCR assay performed on an ABI PRISM 7700 Sequence
      Detection System (TaqMan). Compared to results of the MTP-PCR, the sensitivity,
      specificity, positive predictive value, and negative predictive value were 70.5,
      97.5, 87.8, and 92.8% for the antigenemia assay and were 96.7, 92.0, 75.6, and
      99.1% for the TaqMan assay, respectively. There was a high correlation between
      antigenemia values and HCMV loads as determined by the TaqMan (r = 0.989; P <
      0.001). Antigenemia values of 0, 1 to 10, 11 to 100, 101 to 1,000, and over 1,000
      positive cells per 2 x 10(5) leukocytes corresponded to median HCMV loads
      measured by TaqMan of 125, 1,593, 5,713, 16,825, and 5,425,000 copies/ml,
      respectively. Corresponding to antigenemia values of 1 to 2, 10, and 50 positive
      cells per 2 x 10(5) leukocytes, HCMV viral loads of 1,000, 4,000, and 10,000
      copies/ml are proposed as cutoff points for initiating antiviral therapy in
      patient groups with high, intermediate, and low risk of CMV diseases.

PMID- 12517847
TI  - Characteristics of Massilia timonae and Massilia timonae-like isolates from human
      patients, with an emended description of the species.
AB  - The description of Massilia timonae, a nonfermentative aerobic gram-negative rod,
      was based on a single strain. A subsequent report of a second isolate has been
      recently published. Phenotypic descriptions of these two strains were based
      primarily on commercial test kit results. We have identified three additional
      strains as M. timonae by 16S rRNA sequence analysis and have characterized them
      phenotypically in parallel with the type strain of M. timonae, CIP 105350, by
      conventional test methods. A fourth strain, designated M. timonae-like, was also
      characterized. All four strains were isolated from human patients: two were blood
      isolates, one was isolated from cerebrospinal fluid, and one was isolated from
      bone. The four strains and the type strain were quite similar phenotypically.
      However, in contrast to the original description, the strains were found to be
      oxidase positive and arginine dihydrolase negative and to have lateral flagella
      as well as a single polar flagellum. Additionally the strains produced acid
      oxidatively from some carbohydrates. Other phenotypic characteristics, including
      cellular fatty acids, agreed with the original description. Based on our emended
      description, M. timonae and M. timonae-like strains can be differentiated from
      other aerobic nonfermentative gram-negative rods by conventional biochemical
      tests combined with cellular fatty acid analysis.

PMID- 12517848
TI  - Genetic diversity of Neisseria gonorrhoeae housekeeping genes.
AB  - Molecular typing of Neisseria gonorrhoeae strains is an important tool for
      epidemiological studies of gonococcal infection and transmission. The recently
      developed multilocus sequence typing (MLST) method is based on the genetic
      variation among housekeeping genes. As a preliminary investigation for the
      development of such a method, we characterized the genetic diversity at 18
      gonococcal housekeeping gene loci. Approximately 17,500 nucleotides, spanning 18
      loci, were sequenced from 24 isolates. Including strain FA 1090, which has been
      fully sequenced, and three unique glnA sequences from GenBank, the number of
      alleles identified for the 18 loci ranged from 2 to 18, with a mean of 8.3
      alleles per locus. The majority of polymorphic sites were distributed randomly
      along the genes, consistent with evolution of DNA sequences by point mutation. In
      addition, several examples of clustered mutations and insertions or deletions
      were detected, which most likely occurred by recombinational events. While
      purifying selection is the dominant force driving the evolution of these
      housekeeping genes, positive selection also appeared to operate on the abcZ and
      gpdh loci. The 25 completely characterized strains each had a unique allelic
      profile with as few as three loci (pilA, abcZ, and pip or pgi2). Molecular typing
      based on the allelic profile of housekeeping genes resolved the isolates better
      than either porB nucleotide sequencing or typing of the opa gene. The allelic
      profiles for the pilA, abcZ, and serC loci of paired strains from 16 sexual
      contacts were identical. A potential MLST for N. gonorrhoeae, based on
      approximately 500- to 600-bp gene fragments of seven housekeeping gene loci,
      would include the pilA, abcZ, serC, glnA, gdh, gnd, and pip loci.

PMID- 12517849
TI  - Nested PCR assays for detection of Blastomyces dermatitidis DNA in paraffin
      embedded canine tissue.
AB  - A Blastomyces dermatitidis nested PCR assay targeting the gene encoding the
      Wisconsin 1 (WI-1) adhesin was developed and compared with a nested PCR targeting
      the 18S rRNA gene (rDNA) of members of the family ONYGENACEAE: We examined 73
      paraffin-embedded tissue samples obtained from nine dogs which died of
      blastomycosis and nine dogs which succumbed to lymphosarcoma according to autopsy
      findings; amplifiable canine DNA was extracted from 25 and 33 specimens from the
      two groups, respectively. The B. dermatitidis PCR amplified DNA from 8 of 13
      tissue samples in which yeast cells were detected by microscopy. Sequencing
      revealed that all PCR products were homologous to the B. dermatitidis WI-1
      adhesin gene. No PCR product was amplified from 12 microscopically negative
      biopsy specimens from dogs with blastomycosis or from 33 biopsy specimens from
      dogs with lymphosarcoma. The 18S rDNA PCR amplified DNA from 10 and 9 tissue
      samples taken from dogs which died of blastomycosis and lymphosarcoma,
      respectively. Only six products were identified as being identical to B.
      dermatitidis 18S rDNA; they were exclusively obtained from specimens positive by
      the B. dermatitidis nested PCR. For specificity testing, 20 human biopsy
      specimens proven to have histoplasmosis were examined, and a specific H.
      capsulatum product was amplified by the 18S rDNA PCR from all specimens, whereas
      no product was obtained from any of the 20 samples by the B. dermatitidis PCR
      assay. In conclusion, the PCR targeting a gene encoding the unique WI-1 adhesin
      is as sensitive as but more specific than the PCR targeting the 18S rDNA for
      detection of B. dermatitidis in canine tissue.

PMID- 12517850
TI  - Commercial assay for detection of Giardia lamblia and Cryptosporidium parvum
      antigens in human fecal specimens by rapid solid-phase qualitative
      immunochromatography.
AB  - The ImmunoCard STAT! Cryptosporidium/Giardia rapid assay (Meridian Bioscience,
      Inc.) is a solid-phase qualitative immunochromatographic assay that detects and
      distinguishes between Giardia lamblia and Cryptosporidium parvum in aqueous
      extracts of human fecal specimens (fresh, frozen, unfixed, or fixed in 5 or 10%
      formalin or sodium acetate-acetic acid-formalin). By using specific antibodies,
      antigens specific for these organisms are isolated and immobilized on a
      substrate. After the addition of appropriate reagents, a positive test is
      detected visually by the presence of a gray-black color bar (regardless of the
      intensity) next to the organism name printed on the test device. A control is
      included in the device. Steps include tube preparation (buffer, patient specimen,
      conjugates A and B), testing (addition of sample onto the test device), and
      visual reading (total time, 12 min). Test performance was evaluated with known
      positive and negative stool specimens (170 specimens positive for Giardia and 231
      specimens negative for Giardia) (85 specimens positive for Cryptosporidium and
      316 specimens negative for Cryptosporidium); they were tested with trichrome,
      iron-hematoxylin, or modified acid-fast stains or the Meridian Bioscience, Inc.,
      Giardia/Cryptosporidium Merifluor combination reagent; specimens with discrepant
      results were retested by using the Merifluor combination reagent. On the basis of
      the results of the reference methods, the sensitivities, specificities, and
      positive and negative predictive values were as follows: for G. lamblia, 93.5,
      100, 100, and 95.5%, respectively; for C. parvum, 98.8, 100, 100, and 99.7%,
      respectively. False-negative results for G. lamblia were obtained with specimens
      with low parasite numbers (n = 7) or specimens containing trophozoites only (n =
      3); one specimen with a false-negative result contained numerous cysts. The one
      specimen false negative for C. parvum was confirmed to be positive by
      immunofluorescence. No cross-reactivity was seen with 10 different protozoa (152
      challenges), nine different helminths (35 challenges), or human cells (4
      challenges) found in fecal specimens. This rapid test system may be very
      beneficial in the absence of trained microscopists; however, for patients who
      remain symptomatic after a negative result, the ova and parasite examination and
      special stains for other coccidia and the microsporidia should always remain
      options.

PMID- 12517851
TI  - Comparison of recovery of blood culture isolates from two BacT/ALERT FAN aerobic
      blood culture bottles with recovery from one FAN aerobic bottle and one FAN
      anaerobic bottle.
AB  - Traditionally, a routine blood culture for adult patients consisted of paired
      aerobic and anaerobic bottles, but the routine use of an anaerobic blood culture
      bottle has been challenged in recent years. In this study, we compared the
      recovery of two FAN aerobic bottles with one FAN aerobic and one FAN anaerobic
      bottle. Each pair of bottles was collected by a separate collection procedure,
      and each bottle held a recommended 8- to 12-ml draw. A total of 704 clinically
      significant isolates were recovered from 8,620 sets (17,240 pairs), with 487
      (69.2%) isolates recovered from one or both bottles in each pair of bottles, 86
      isolates (12.2%) recovered only from the FAN aerobic-FAN aerobic pair, and 131
      isolates (18.6%) recovered only from the FAN aerobic-FAN anaerobic pair.
      Significantly more total organisms (P = 0.002), gram-positive cocci (P = 0.03),
      Staphylococcus aureus (P = 0.05), Enterobacteriaceae other than Escherichia coli
      (P = 0.02), and anaerobes (P = 0.01) were recovered from the FAN aerobic-FAN
      anaerobic pair than from the FAN aerobic-FAN aerobic pair. A separate analysis
      was performed on the 618 isolates that were recovered from the FAN aerobic-FAN
      anaerobic pair to compare recovery by bottle type. Significantly more S. aureus
      (P = 0.005) and anaerobes (P < 0.001) were recovered from the FAN anaerobic
      bottle, while significantly more coagulase-negative staphylococci (P = 0.01),
      Streptococcus pneumoniae (P = 0.03), and other gram-negative bacilli (P = 0.004)
      were recovered from the FAN aerobic bottle. These results support the routine use
      of a FAN anaerobic bottle for use in the culture of blood with the BacT/ALERT
      system in our institution. These results also suggest that the decision of
      whether to routinely utilize an anaerobic blood culture bottle should be
      influenced by the overall recovery of bacteria and yeast, the recovery of
      specific types of bacteria or yeast, the medium type, and the blood culture
      system utilized by the laboratory.

PMID- 12517852
TI  - Extended virulence genotype of pathogenic Escherichia coli isolates carrying the
      afa-8 operon: evidence of similarities between isolates from humans and animals
      with extraintestinal infections.
AB  - The afimbrial AfaE-VIII adhesin is common among Escherichia coli isolates from
      calves with intestinal and/or extraintestinal infections and from humans with
      sepsis or pyelonephritis. The virulence genotypes of 77 Escherichia coli afa-8
      isolates from farm animals and humans were compared to determine whether any
      trait of commonality exists between isolates of the different host species. Over
      half of the extraintestinal afa-8 isolates were associated with pap and f17Ac
      adhesin genes and contained virulence genes (pap, hly, and cnf1) which are
      characteristic of human extraintestinal pathogenic E. coli (ExPEC). PapG, which
      occurs as three known variants (variants I to III), is encoded by the
      corresponding three alleles of papG. Among the pap-positive strains, new papG
      variants (papGrs) that differed from the isolates with genes for the three
      adhesin classes predominated over isolates with papG allele III, which in turn
      were more prevalent than those with allele II. The data showed the substantial
      prevalence of the enteroaggregative E. coli heat-stable enterotoxin gene (east1)
      among afa-8 isolates. Most of the afa-8 isolates harbored the high-pathogenicity
      island (HPI) present in pathogenic Yersinia; however, two-thirds of the HPI
      positive strains shared a truncated HPI integrase gene. The presence of ExPEC
      associated virulence factors (VFs) in extraintestinal isolates that carry genes
      typical of enteric strains and that express O antigens associated with intestinal
      E. coli is consistent with transfer of VFs and O-antigen determinants between
      ExPEC and enteric strains. The similarities between animal and human ExPEC
      strains support the hypothesis of overlapping populations, with members of
      certain clones or clonal groups including animal and human strains. The presence
      of multiple-antibiotic-resistant bovine afa-8 strains among such clones may
      represent a potential public health risk.

PMID- 12517853
TI  - Quality assessment program for genotypic antiretroviral testing improves
      detection of drug resistance mutations.
AB  - Genotypic antiretroviral testing is now widely used for the management of
      patients who are undergoing antiretroviral therapy for human immunodeficiency
      virus infection. The assays are complex, and there is considerable potential for
      variation between laboratories. Informative and ongoing quality assessment
      programs (QAPs) which address all aspects of testing are required. The panel
      distribution of clinical material is a critical component of QAPs. We report on
      the results and data from a recent panel. Four cryopreserved plasma samples from
      treated donors were distributed to nine laboratories. Three laboratories
      performed testing by commercial assays, and six laboratories used in-house
      assays, with one laboratory reporting results from two in-house assays. There was
      complete concordance between results for 95.9% of the nucleotide sequence and
      94.5% of the amino acid sequence. Despite this overall high level of concordance,
      the degree of concordance at drug resistance mutation (DRM) sites when DRMs were
      present was considerably less (38% of DRM sites). Consequently, only 3 of the 10
      methods reported 100% of DRMs as present. This elevated discrepancy rate is
      almost certainly a result of variability in the identification of mixtures of
      nucleotides (mixtures) at any site within the sequence. In addition, laboratories
      differed in the number of codons in the reverse transcriptase gene that were
      sequenced and their ability to amplify all samples. This panel distribution
      demonstrated a requirement for laboratory participation in ongoing QAPs and the
      optimization of assays with standards that contain mixtures.

PMID- 12517854
TI  - Detection and differentiation of Entamoeba histolytica and Entamoeba dispar
      isolates in clinical samples by PCR and enzyme-linked immunosorbent assay.
AB  - Differential diagnosis of Entamoeba histolytica (pathogenic) and Entamoeba dispar
      (nonpathogenic), which are two morphologically identical species of amebae, is
      essential both for treatment decision and public health knowledge. The study
      reported here was designed to choose a reference differentiation technique. Stool
      samples (n = 95) were tested by microscopy, TechLab enzyme-linked immunosorbent
      assays (ELISAs), and an in-house PCR. The target for the PCR amplification was a
      small region (135 bp) of the SSU rRNA selected to increase the sensitivity of the
      test. Sixty-eight specimens tested positive by PCR: 2 for E. histolytica and 66
      for E. dispar. For detection of E. dispar, ELISA performance was lower than that
      of microscopy in this reference context, while PCR was much more sensitive than
      microscopy. Given the low proportion of E. histolytica cases, test performance
      for this species is difficult to assess. However, for differentiation, PCR
      performed well on simulated samples, while ELISA gave a discordant result for one
      of the two samples PCR positive for E. histolytica during the study. This report
      also confirms that E. dispar infection is significantly higher among travelers
      and underlines the possibility of acquiring E. histolytica infection in regions
      that are not areas of endemicity. Because of its lower sensitivity, the interest
      of ELISA for Entamoeba detection and differentiation in stools seems questionable
      in nontropical regions. On the other hand, results suggest that PCR should be
      useful as a reference test for sensitive differentiation of both species and to
      contribute to physicians' decision in treatment of E. histolytica- or E. dispar
      infected patients.

PMID- 12517855
TI  - Comparison of LightCycler PCR, rapid antigen immunoassay, and culture for
      detection of group A streptococci from throat swabs.
AB  - We compared the performance characteristics of a real-time PCR method, the
      LightCycler Strep-A assay (Roche Applied Science, Indianapolis, Ind.), to those
      of a rapid antigen immunoassay, the Directigen 1-2-3 Group A Strep Test kit (BD
      Diagnostic Systems, Sparks, Md.), and a standard culture method for detection of
      group A streptococci (GAS) from 384 throat swabs. The LightCycler PCR produced
      more positive results (n = 58) than either culture (n = 55) or the Directigen
      immunoassay (n = 31). The results of the LightCycler PCR and the Directigen
      method were independently compared to the results of the accepted "gold
      standard," bacterial culture. The sensitivities, specificities, and positive and
      negative predictive values for this comparison were as follows: for the
      Directigen method, 55, 99, 97, and 93%, respectively; for the LightCycler PCR,
      93, 98, 88, and 99%, respectively. In no case was a throat swab positive by both
      the LightCycler PCR and the Directigen method but negative by culture. The
      medical histories of patients whose throat swabs were negative by culture but
      positive by either the LightCycler PCR (n = 7) or the Directigen method (n = 1)
      were reviewed. All of these patients had signs or symptoms compatible with GAS
      disease, and therefore, all of these discordant positive results (along with
      positive results by either the Directigen method or the LightCycler PCR that
      agreed with the culture results) were counted as true positives for statistical
      analysis. For this analysis, the LightCycler PCR detected more true-positive
      results than the culture method (58 versus 55 swabs); however, this difference
      was not statistically significant (P = 0.5465). In contrast, statistically
      significantly more true-positive results occurred by culture than by the
      Directigen method (55 versus 31 swabs; P < 0.0001) and by the LightCycler PCR
      than by the Directigen method (58 versus 31 swabs; P < 0.0001). The LightCycler
      PCR is a suitable stand-alone method for the detection of GAS from throat swabs.
      Additionally, this method requires less than half the personnel time and the
      procedure can be completed in considerably less time ( approximately 1 h) than
      our standard approach (up to 2 days) for detection of GAS in throat swabs (i.e.,
      testing by the Directigen method with negative results verified by culture).

PMID- 12517856
TI  - Evaluation of an enzyme immunoassay technique for detection of antibodies against
      Treponema pallidum.
AB  - In the present study, the performance of an enzyme-linked immunosorbent assay
      (ELISA) technique (Eti-syphilis-G and Eti-syphilis-M; DiaSorin) for detection of
      Treponema pallidum immunoglobulin M (IgM) and IgG antibodies for the laboratory
      diagnosis of syphilis was evaluated. Four hundred forty-one samples were studied.
      The sensitivity and specificity of the ELISA were 100 and 93%, respectively,
      compared with the results of a microhemagglutination assay for Treponema pallidum
      (MHA-TP) and 99.4 and 100%, respectively, compared with the results of the
      fluorescent treponemal antibody absorption (FTA-Abs) test. The results of the
      ELISA technique were concordant with those of MHA-TP for 98% of the samples
      tested, while the rate of concordance with the FTA-Abs test was 99.5%. The
      sensitivities of the rapid plasma reagin (RPR) test, MHA-TP, and the ELISA in the
      different phases of syphilis compared with the results of the FTA-Abs test were
      92, 88, and 100%, respectively, for patients with primary syphilis; 100% for all
      tests evaluated for patients with secondary syphilis; 97.2, 99.4, and 100%,
      respectively, for patients with latent syphilis; and 57.9, 92.6, and 97.9%,
      respectively, for patients with past treated syphilis. The RPR test was reactive
      with 12 samples that were negative by all the specific tests. IgM antibodies were
      most frequently detected by the ELISA for IgM antibodies (32.8%) than by the FTA
      Abs for IgM antibodies (28.4%). Detection of these antibodies by the FTA-Abs test
      and the ELISA for IgM antibodies decreased with the stage of disease (72 and 88%,
      respectively, for patients with primary syphilis to 17 and 19%, respectively, for
      patients with early latent syphilis). The high sensitivity and specificity of
      this ELISA technique during all stages of syphilis, together with the fact that
      it is a simple, objective, and easily automated method, lead us to believe that
      it could be used as a screening test for syphilis.

PMID- 12517857
TI  - Rapid detection of methicillin-resistant Staphylococcus aureus directly from
      sterile or nonsterile clinical samples by a new molecular assay.
AB  - A rapid procedure was developed for detection and identification of methicillin
      resistant Staphylococcus aureus (MRSA) directly from sterile sites or mixed flora
      samples (e.g., nose or inguinal swabs). After a rapid conditioning of samples,
      the method consists of two main steps: (i) immunomagnetic enrichment in S. aureus
      and (ii) amplification-detection profile on DNA extracts using multiplex
      quantitative PCR (5'-exonuclease qPCR, TaqMan). The triplex qPCR assay measures
      simultaneously the following targets: (i) mecA gene, conferring methicillin
      resistance, common to both S. aureus and Staphylococcus epidermidis; (ii) femA
      gene from S. aureus; and (iii) femA gene from S. epidermidis. This quantitative
      approach allows discrimination of the origin of the measured mecA signal. qPCR
      data were calibrated using two reference strains (MRSA and methicillin-resistant
      S. epidermidis) processed in parallel to clinical samples. This 96-well format
      assay allowed analysis of 30 swab samples per run and detection of the presence
      of MRSA with exquisite sensitivity compared to optimal culture-based techniques.
      The complete protocol may provide results in less than 6 h (while standard
      procedure needs 2 to 3 days), thus allowing prompt and cost-effective
      implementation of contact precautions.

PMID- 12517858
TI  - Detection of Mycoplasma genitalium by PCR amplification of the 16S rRNA gene.
AB  - In order to develop a species-specific PCR for the detection of Mycoplasma
      genitalium, the sequence of 1,490 bases of the 16S rRNA gene was determined for
      M. genitalium G37 (type strain) and four Danish isolates of M. genitalium. The
      sequences of the four Danish strains, mutually different with respect to their
      MgPa gene, were 100% homologous, although they carried a single common base
      substitution compared to the type strain. Among members of the Mycoplasma
      pneumoniae phylogenetic cluster, M. genitalium showed the most-prominent homology
      to the 16S rRNA sequence of M. pneumoniae (98% homology). From regions showing
      the least homology to the M. pneumoniae 16S rRNA gene sequence, primers were
      chosen to amplify DNA from M. genitalium only. Two sets of primers were selected
      for their ability to detect <10 to 50 M. genitalium genome copies without cross
      reactions with M. pneumoniae. The performance of these primers was compared to
      the performance of two pairs of primers amplifying parts of the MgPa adhesin
      gene; 1,030 randomly selected specimens submitted for Chlamydia trachomatis
      culture were screened with one of the 16S rRNA gene primer sets. A total of 41
      specimens were found to be positive for this gene; 40 of these could be confirmed
      by one of the MgPa primer sets, whereas the other MgPa primer set detected only
      21 positive specimens out of 40. These results indicate that estimates of the
      prevalence of M. genitalium in various populations using MgPa PCR primers could
      be incorrectly low if the PCR primers are located in variable regions of the MgPa
      gene.

PMID- 12517859
TI  - Characterization of heteroresistance to fluconazole among clinical isolates of
      Cryptococcus neoformans.
AB  - Strains of Cryptococcus neoformans expressing heteroresistance to fluconazole
      have been described previously. The present study was conducted to investigate
      the prevalence of heteroresistance among clinical isolates of C. neoformans and
      to characterize the heteroresistant phenotypes. A total of 107 clinical isolates
      of C. neoformans for which the MICs of fluconazole ranged from 0.25 to 32
      microg/ml were selected. The isolates were chosen to represent a broad geographic
      distribution. Of the 107 C. neoformans isolates tested, 4 grew on medium
      containing fluconazole at concentrations that were four to eight times higher
      than the MICs for each strain. A fifth isolate, for which the fluconazole MIC was
      32 microg/ml, grew on agar with 64 microg of fluconazole per ml. These five
      isolates (4.7% of the total number) were confirmed to exhibit heteroresistant
      compositions by population analysis. The degree and frequency of resistance
      varied among the isolates. Stepwise selection by exposure to fluconazole resulted
      in subclones of all five strains for which the fluconazole MIC was >64 microg/ml.
      Subclones of three strains demonstrated a homogeneous population of resistant
      cells on medium containing 64 microg of fluconazole/ml. The resistance was
      sensitive to incubation temperature, that is, heteroresistance was demonstrable
      only at 30 degrees C by agar-based tests, and was reversible through serial
      transfers on fluconazole-free medium over a period of 8 days. These results
      suggest that the fluconazole-heteroresistant phenotype of C. neoformans exists in
      a significant proportion of clinical isolates and that fluconazole resistance can
      be developed by selection from heteroresistant clones and induction by exposure
      to fluconazole.

PMID- 12517860
TI  - Nonencapsulated Neisseria meningitidis strain produces amylopectin from sucrose:
      altering the concept for differentiation between N. meningitidis and N.
      polysaccharea.
AB  - Neisseria meningitidis is the causative agent of meningococcal sepsis and
      meningitis. Neisseria polysaccharea is a nonpathogenic species. N. polysaccharea
      is able to use sucrose to produce amylopectin, a starch-like polysaccharide,
      which distinguishes it biochemically from the pathogenic species N. meningitidis.
      The data presented here indicate that this may be an insufficient criterion to
      distinguish between these two species. The nonencapsulated Neisseria strain 93246
      expressed a phenotype of amylopectin production similar to that of N.
      polysaccharea. However, strain 93246 reacted with N. meningitidis serotype 4 and
      serosubtype P1.14 monoclonal antibodies and showed the N. meningitidis L1(8) lipo
      oligosaccharide immunotype. Further analyses were performed on four genetic loci
      in strain 93246, and the results were compared with 7 N. meningitidis strains, 13
      N. polysaccharea strains, and 2 N. gonorrhoeae strains. Three genetic loci, opcA,
      siaD, and lgt-1 in strain 93246, were the same as in N. meningitidis.
      Particularly, the siaD gene encoding polysialyltransferase responsible for
      biosynthesis of N. meningitidis group B capsule was detected in strain 93246.
      This siaD gene was inactivated by a frameshift mutation at the poly(C) tract,
      which makes strain 93246 identical to other nonencapsulated N. meningitidis
      strains. As expected, the ams gene encoding amylosucrase, responsible for
      production of amylopectin from sucrose, was detected in strain 93246 and all 13
      N. polysaccharea strains but not in N. meningitidis and N. gonorrhoeae strains.
      These data suggest that strain 93246 is nonencapsulated N. meningitidis but has
      the ability to produce extracellular amylopectin from sucrose. The gene for
      amylopectin production in strain 93246 was likely imported from N. polysaccharea
      by horizontal genetic exchange. Therefore, we conclude that genetic analysis is
      required to complement the traditional phenotypic classification for the
      nonencapsulated Neisseria strains.

PMID- 12517861
TI  - Evaluation of a novel automated chemiluminescent assay system for antimicrobial
      susceptibility testing.
AB  - The newly developed Rapid Lumi Eiken/IS60 (RL/IS60) system automatically
      determines MICs by detecting chemiluminescence produced in the reaction of a
      chemiluminescent probe and oxygen metabolites from living microorganisms. The
      present study evaluated this system for accuracy in antimicrobial susceptibility
      testing. Chemiluminescence intensities after 4 h of cultivation of clinically
      important strains were plotted against various concentrations of antimicrobial
      agents, which resulted in curves reflecting the levels of susceptibility. Sixty
      percent inhibitory concentrations based on the susceptibility curves agreed with
      MICs determined by the reference microdilution method. When the MICs of
      antimicrobial agents for four quality control (QC) strains (Staphylococcus
      aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa) were
      determined by the RL/IS60 system, most (91.1%) of them were within the QC limits
      proposed by the National Committee for Clinical Laboratory Standards. The system
      was further assessed for a total of 162 clinical isolates, including E. coli,
      Citrobacter freundii, Enterobacter cloacae, Klebsiella pneumoniae, Serratia
      marcescens, Proteus mirabilis, Morganella morganii, P. aeruginosa, Haemophilus
      influenzae, S. aureus, coagulase-negative staphylococci, Enterococcus faecalis,
      Enterococcus faecium, and Streptococcus pneumoniae. Overall, there was 90.6%
      agreement between the RL/IS60 system and the reference microdilution method. Our
      results suggest that the RL/IS60 system provides rapid and reliable MICs of a
      variety of antimicrobial agents for clinical isolates as well as QC strains.

PMID- 12517862
TI  - Identification of a gene encoding heat-resistant agglutinin in Escherichia coli
      as a putative virulence factor in urinary tract infection.
AB  - Escherichia coli causes the vast majority of urinary tract infections (UTI) in
      both ambulatory and hospital patients. Several uropathogenic virulence factors
      have been identified, but half of all E. coli isolates that cause UTI have none
      or only one of the known virulence factors. Thus, it is reasonable to presume
      that other bacterial factors may be important in UTI pathogenesis. In order to
      find additional uropathogenic E. coli genes, we used genomic subtraction to
      identify DNA regions present in a uropathogenic strain of E. coli (1128-11).
      Genomic subtraction yielded 40 tester-specific fragments, including a novel heat
      resistant agglutinin (hra) gene fragment. hra occurred in 55% of 486 UTI strains
      compared to 28% of 165 rectal strains (P = 0.001). The hra gene in 1128-11 was
      cloned, sequenced, and found to have 91% homology to the hra gene from E. coli
      meningitis strain RS218. The genetic organization of genes flanking hra in 1128
      11 is distinct from the hra found in E. coli strains J96 and RS218. In our UTI
      and rectal specimen collections, hra was positively associated with a number of
      known virulence genes, including pathogenicity island genes hly and cnf, which
      are absent in 1128-11. The presence of hra in 1128-11 independent of hly/cnf
      suggests multiple mechanisms by which hra can be acquired by pathogenic E. coli
      strains. The flanking genes suggest that in 1128-11, hra may be part of a novel
      variant of a pathogenicity island V.

PMID- 12517863
TI  - Evaluation of a human group a rotavirus assay for on-site detection of bovine
      rotavirus.
AB  - Neonatal diarrhea induced by bovine group A rotavirus causes significant economic
      loss in the dairy and beef industry due to increased morbidity and mortality,
      treatment costs, and reduced growth rates. The objective of this study was to
      evaluate a human group A rotavirus assay (ImmunoCardSTAT Rotavirus [ICS-RV]) as
      an on-site diagnostic test for bovine rotavirus. When used with a collection of
      bovine diarrhea samples submitted to the Virology Section of the Diagnostic
      Center for Population and Animal Health at Michigan State University and compared
      to a bovine group A rotavirus-specific reverse transcription-PCR (RT-PCR), the
      ICS-RV assay had a sensitivity and specificity of 87.0 and 93.6%, respectively. A
      commercially available group A rotavirus enzyme-linked immunosorbent assay
      (ELISA) (Pathfinder; Sanofi Diagnostics, Redmond, Wash.), when used with the same
      fecal sample collection and compared to the same RT-PCR, had a sensitivity and
      specificity of 78.3 and 67.7%, respectively. Subsequently, the ICS-RV assay, RT
      PCR, and a different commercially available group A rotavirus ELISA (Rotaclone;
      Meridian Diagnostics, Cincinnati, Ohio) were used to evaluate fecal samples
      collected from neonatal calves experimentally infected with bovine rotavirus.
      When diarrheic fecal samples that were positive for bovine rotavirus by RT-PCR
      were evaluated, the ICS-RV assay and the Rotaclone assay detected bovine
      rotavirus 85 and 95% of the time, respectively. Based on these studies, the ICS
      RV assay appears to be an excellent test for detecting group A bovine
      rotaviruses. This assay may be useful as an on-site diagnostic test for
      veterinarians as an aid in the management of bovine neonatal diarrhea.

PMID- 12517864
TI  - Culture-independent molecular analysis of microbial constituents of the healthy
      human outer ear.
AB  - Molecular-phylogenetic sequence analyses have provided a new perspective on
      microbial communities by allowing the detection and identification of constituent
      microorganisms in the absence of cultivation. In this study we used broad
      specificity amplification of ribosomal DNA (rDNA) genes to survey organisms
      present in the human outer ear canal. Samples were obtained from 24 individuals,
      including members of three extended families, in order to survey the resident
      microbiota and to examine microbial population structures in individuals related
      by familial or household associations. To examine the stability of the microbial
      populations, one individual was sampled four times and another twice over a 14
      month period. We found that a distinct set of microbial types was present in the
      majority of the subjects sampled. The two most prevalent rDNA sequence types that
      were identified in multiple individuals corresponded closely to those of
      Alloiococcus otitis and Corynebacterium otitidis, commonly thought to be
      associated exclusively with infections of the middle ear. Our results suggest,
      therefore, that the outer ear canal may serve as a reservoir for normally
      commensal microbes that can contribute to pathogenesis upon introduction into the
      middle ear. Alternatively, culture analyses of diseases of the middle ear may
      have been confounded by these contaminating commensal organisms.

PMID- 12517865
TI  - Performance of the APTIMA Combo 2 assay for detection of Chlamydia trachomatis
      and Neisseria gonorrhoeae in female urine and endocervical swab specimens.
AB  - The greater sensitivity of nucleic acid amplification tests (NAATs) for Chlamydia
      trachomatis and Neisseria gonorrhoeae permits the use of urine and other
      noninvasive specimens, which can increase the reach and decrease the costs of
      public health screening programs aimed at controlling these infections. This
      study evaluated the performance of the APTIMA Combo 2 assay, a multiplex assay
      based on the transcription-mediated amplification reaction, for the simultaneous
      detection of both pathogens in endocervical swab and urine specimens from
      females. Combo 2 assay results were compared with patient infected status, which
      were available by using other commercial NAATs. Sensitivity and specificity for
      C. trachomatis were 94.2 and 97.6%, respectively, in swabs and 94.7 and 98.9%,
      respectively, in first-catch urine (FCU). Sensitivity and specificity for N.
      gonorrhoeae were 99.2 and 98.7%, respectively, in swabs and 91.3 and 99.3%,
      respectively, in FCU. The assay reliably detected both infections in coinfected
      patients. The Combo 2 assay can be recommended for use with endocervical swab and
      urine specimens from females, especially for screening tests for asymptomatic
      women in sexually transmitted disease surveillance programs. This Food and Drug
      Administration-cleared assay can be a useful tool in efforts to reduce the
      prevalence and incidence of C. trachomatis and N. gonorrhoeae infections in
      sexually active women and to prevent their costly and serious sequelae.

PMID- 12517866
TI  - Performance evaluation of the VERSANT HCV RNA qualitative assay by using
      transcription-mediated amplification.
AB  - A preclinical evaluation of a qualitative assay for the detection of hepatitis C
      virus (HCV) RNA by transcription-mediated amplification (TMA) was conducted
      according to the guidelines of the National Committee for Clinical Laboratory
      Standards and the U.S. Food and Drug Administration. Our results showed that this
      assay, HCV TMA, detected 95% of samples with HCV RNA concentrations of 5.3 IU/ml
      and 29 copies/ml. HCV TMA showed an overall specificity of 99.6% and was highly
      reproducible, detecting 99.3% of samples with HCV RNA concentrations of 50
      copies/ml across seven different lots of reagents. Experiments with clinical
      samples showed that HCV TMA detected all HCV genotypes with similar efficiencies,
      detecting > or = 95% of samples at 50 HCV RNA copies/ml from patients infected
      with HCV genotypes 1a, 2b, 3a, 4a, 5a, and 6a. In experiments with RNA
      transcripts, HCV TMA detected > or = 96.6% of transcripts derived from HCV
      genotypes 1a, 1b, 2a, 2c, 3a, 4a, 5a, and 6a at 50 HCV RNA copies/ml. Detection
      of transcripts derived from HCV genotype 2b was slightly lower (88.4%) at 50
      copies/ml but was 97.0% at 75 copies/ml. In addition, HCV TMA exhibited robust
      performance in detecting HCV RNA in samples subjected to various conditions
      commonly encountered in a clinical laboratory, including long-term storage,
      multiple freeze-thaw cycles, different collection tubes, and the presence of
      endogenous substances, commonly prescribed drugs, or other microorganisms and
      viruses. With its high sensitivity, specificity, reproducibility, and equivalent
      genotype reactivity, HCV TMA may provide an attractive alternative for routine
      qualitative HCV RNA testing in clinical laboratories.

PMID- 12517867
TI  - Validation of a urine-based PCR-enzyme-linked immunosorbent assay for use in
      clinical research settings to detect Trichomonas vaginalis in men.
AB  - Trichomonas vaginalis infection is highly prevalent worldwide and is associated
      with urethritis, prostatitis, and urethral strictures in men. However, the
      natural history and importance of T. vaginalis in men are poorly understood, in
      part because of difficulties in diagnosing infection. Traditional detection
      methods rely on culture and wet-mount microscopy, which can be insensitive and
      time consuming. Urethral swabs are commonly used to detect T. vaginalis in men,
      but discomfort from specimen collection is a barrier to large studies. One
      thousand two hundred twenty-five Malawian men attending sexually transmitted
      disease and dermatology clinics were enrolled in this cross-sectional study to
      validate detection by urine-based PCR-enzyme-linked immunosorbent assay (ELISA)
      with urine and urethral swab culture as the reference standard. This assay for
      detection of amplified T. vaginalis DNA in first-catch urine (< or = 30 ml)
      performed with a sensitivity of 92.7%, a specificity of 88.6%, and an adjusted
      specificity of 95.2% compared to culture of urethral swabs or urine sediment. For
      clinical research settings in which urethral swabs are not available and culture
      is not feasible, the urine-based PCR-ELISA may be useful for detection of
      trichomoniasis in men.

PMID- 12517868
TI  - Prospective study of the performance of vibrational spectroscopies for rapid
      identification of bacterial and fungal pathogens recovered from blood cultures.
AB  - Rapid identification of microbial pathogens reduces infection-related morbidity
      and mortality of hospitalized patients. Raman spectra and Fourier transform
      infrared (IR) spectra constitute highly specific spectroscopic fingerprints of
      microorganisms by which they can be identified. Little biomass is required, so
      that spectra of microcolonies can be obtained. A prospective clinical study was
      carried out in which the causative pathogens of bloodstream infections in
      hospitalized patients were identified. Reference libraries of Raman and IR
      spectra of bacterial and yeast pathogens highly prevalent in bloodstream
      infections were created. They were used to develop identification models based on
      linear discriminant analysis and artificial neural networks. These models were
      tested by carrying out vibrational spectroscopic identification in parallel with
      routine diagnostic phenotypic identification. Whereas routine identification has
      a typical turnaround time of 1 to 2 days, Raman and IR spectra of microcolonies
      were collected 6 to 8 h after microbial growth was detected by an automated blood
      culture system. One hundred fifteen samples were analyzed by Raman spectroscopy,
      of which 109 contained bacteria and 6 contained yeasts. One hundred twenty-one
      samples were analyzed by IR spectroscopy. Of these, 114 yielded bacteria and 7
      were positive for yeasts. High identification accuracy was achieved in both the
      Raman (92.2%, 106 of 115) and IR (98.3%, 119 of 121) studies. Vibrational
      spectroscopic techniques enable simple, rapid, and accurate microbial
      identification. These advantages can be easily transferred to other applications
      in diagnostic microbiology, e.g., to accelerate identification of fastidious
      microorganisms.

PMID- 12517869
TI  - Evaluation of 11 PCR assays for species-level identification of Campylobacter
      jejuni and Campylobacter coli.
AB  - We examined the sensitivity and specificity of 11 PCR assays described for the
      species identification of Campylobacter jejuni and Campylobacter coli by using
      111 type, reference, and field strains of C. jejuni, C. coli, and Campylobacter
      lari. For six assays, an additional 21 type strains representing related
      Campylobacter, Arcobacter, and Helicobacter species were also included. PCR tests
      were initially established in the laboratory by optimizing conditions with
      respect to five type and reference strains of C. jejuni, C. coli, and C. lari.
      One PCR test for C. coli failed to give appropriate results during this initial
      setup phase and was not evaluated further. The remaining 10 assays were used to
      examine heated lysate and purified DNA templates as appropriate of well
      characterized type, reference, and field strains of C. jejuni (n = 62), C. coli
      (n = 34), and C. lari (n = 15). The tests varied considerably in their
      sensitivity and specificity for their respective target species. No assay was
      found to be 100% sensitive and/or specific for all C. jejuni strains tested, but
      four assays for C. coli gave appropriate responses for all strains examined.
      Between one and six strains of C. jejuni gave amplicons in four of seven C.
      jejuni PCR tests only where purified DNA was used as the template; corresponding
      results were seen with one strain of C. coli in each of three assays for the
      latter species. Our findings indicate that a polyphasic strategy for PCR-based
      identification should be used to identify C. jejuni and C. coli strains. The data
      may assist laboratories in selecting assays suited for their needs and in
      designing evaluations of future PCR tests aimed to identify these species.

PMID- 12517871
TI  - Rapid enterovirus RNA detection in clinical specimens by using nucleic acid
      sequence-based amplification.
AB  - Enterovirus (EV) detection by nucleic acid sequence-based amplification was
      compared with EV isolation in cell culture. The NucliSens Basic kit (bioMerieux)
      was utilized for RNA detection. For virus isolation, samples were inoculated into
      MRC-5, primary rhesus monkey kidney, A549, rhabdomyosarcoma, and/or Buffalo green
      monkey kidney cells.

PMID- 12517870
TI  - Identification of urovirulence traits in Escherichia coli by comparison of
      urinary and rectal E. coli isolates from dogs with urinary tract infection.
AB  - Spontaneously occurring urinary tract infection (UTI) in dogs was exploited as an
      experiment of nature to gain insights into UTI pathogenesis in humans. Concurrent
      urinary and rectal Escherichia coli isolates from 37 dogs with UTI were compared
      with respect to phylogenetic background, O antigens, and extended virulence
      genotype. In 54% of the UTI episodes, the dog's urinary and rectal isolates
      represented the same strain. Urinary isolates differed dramatically from rectal
      only isolates in that they derived predominantly from E. coli phylogenetic group
      B2, expressed typical (human) UTI-associated O antigens, and possessed many
      virulence-associated genes, most notably pap elements (P fimbriae), papG
      (adhesin) allele III, sfa/foc and sfaS (S fimbriae), hly (hemolysin), fyuA
      (yersiniabactin), iroN (siderophore), and ompT (outer membrane protease T). The
      20 urinary isolates that corresponded with the host's predominant rectal strain
      were no less virulent according to the markers analyzed than were the 17 urinary
      isolates that differed from the host's predominant rectal strain. These findings
      suggest that UTI pathogenesis is similar in dogs and humans, provide added
      support for the special-pathogenicity over the prevalence hypothesis of UTI
      pathogenesis, and identify numerous specific virulence-associated factors as
      significant correlates of urovirulence.

PMID- 12517872
TI  - Antimicrobial susceptibility testing of carbapenems: multicenter validity testing
      and accuracy levels of five antimicrobial test methods for detecting resistance
      in Enterobacteriaceae and Pseudomonas aeruginosa isolates.
AB  - From January 1996 to May 1999, Project ICARE (Intensive Care Antimicrobial
      Resistance Epidemiology) received 448 nonduplicate clinical isolates of
      Enterobacteriaceae and Pseudomonas aeruginosa that were reported to be imipenem
      intermediate or resistant. However, broth microdilution (BMD) confirmatory
      testing at the Project ICARE central laboratory confirmed this result in only 11
      of 123 (8.9%) Enterobacteriaceae isolates and 241 of 325 (74.2%) P. aeruginosa
      isolates. To investigate this overdetection of imipenem resistance, we tested 204
      selected isolates from the Project ICARE collection plus five imipenem-resistant
      challenge strains at the Centers for Disease Control and Prevention against
      imipenem and meropenem by agar dilution, disk diffusion, Etest (AB BIODISK North
      America, Inc., Piscataway, N.J.), two MicroScan WalkAway conventional panels (Neg
      MIC Plus 3 and Neg Urine Combo 3) (Dade MicroScan, Inc., West Sacramento,
      Calif.), and two Vitek cards (GNS-116 containing meropenem and GNS-F7 containing
      imipenem) (bioMerieux Vitek, Inc., Durham, N.C.). The results of each test method
      were compared to the results of BMD testing using in-house-prepared panels. Seven
      imipenem-resistant and five meropenem-resistant isolates of Enterobacteriaceae
      and 43 imipenem-resistant and 21 meropenem-resistant isolates of P. aeruginosa
      were identified by BMD. For Enterobacteriaceae, the imipenem and meropenem test
      methods produced low numbers of very major and major errors. All test systems in
      the study produced low numbers of very major and major errors when P. aeruginosa
      was tested against imipenem and meropenem, except for Vitek testing (major error
      rate for imipenem, 20%). Further testing conducted in 11 of the participating
      ICARE hospital laboratories failed to pinpoint the factors responsible for the
      initial overdetection of imipenem resistance. However, this study demonstrated
      that carbapenem testing difficulties do exist and that laboratories should
      consider using a second, independent antimicrobial susceptibility testing method
      to validate carbapenem-intermediate and -resistant results.

PMID- 12517874
TI  - Attempted isolation of Nanobacterium sp. microorganisms from upper urinary tract
      stones.
AB  - A single team has reported isolation of nanobacteria in human and bovine blood
      products, as well as, more recently, kidney stones. This has raised controversy.
      To confirm the data, we searched for nanobacteria from 10 aseptically removed
      upper urinary tract (UUT) stones. We used scanning electronic microscopy (SEM)
      with four stones and culture of stones on either 3T6 fibroblast monolayers or
      liquid RPMI medium. Detection of nanobacteria was made with a commercially
      available monoclonal antibody, 16S ribosomal DNA amplification with specific
      primers, and transmission electronic microscopy (TEM) of inoculated cells. SEM
      showed nanoparticles in four of four UUT stones similar to those recently
      described. TEM of inoculated 3T6 cell monolayers has shown transient
      intracytoplasmic vacuolar formations containing 200- to 500-nm particles in 3 of
      10 cell cultures. Gimenez staining, Hoechst staining, and specific monoclonal
      immunofluorescence failed to reveal nanobacteria. Finally, we could not grow
      Nanobacterium sp. microorganisms by the techniques described. Although with SEM,
      we observed nanoparticles morphologically similar to nanobacteria, we failed to
      isolate Nanobacterium sp. microorganisms in culture and to prove the bacterial
      nature of these nanoparticles in stones.

PMID- 12517873
TI  - Characterization of Mycobacterium tuberculosis complex DNAs from Egyptian mummies
      by spoligotyping.
AB  - Bone and soft tissue samples from 85 ancient Egyptian mummies were analyzed for
      the presence of ancient Mycobacterium tuberculosis complex DNA (aDNA) and further
      characterized by spoligotyping. The specimens were obtained from individuals from
      different tomb complexes in Thebes West, Upper Egypt, which were used for upper
      social class burials between the Middle Kingdom (since ca. 2050 BC) and the Late
      Period (until ca. 500 BC). A total of 25 samples provided a specific positive
      signal for the amplification of a 123-bp fragment of the repetitive element
      IS6110, indicating the presence of M. tuberculosis DNA. Further PCR-based tests
      for the identification of subspecies failed due to lack of specific amplification
      products in the historic tissue samples. Of these 25 positive specimens, 12 could
      be successfully characterized by spoligotyping. The spoligotyping signatures were
      compared to those in an international database. They all show either an M.
      tuberculosis or an M. africanum pattern, but none revealed an M. bovis-specific
      pattern. The results from a Middle Kingdom tomb (used exclusively between ca.
      2050 and 1650 BC) suggest that these samples bear an M. africanum-type specific
      spoligotyping signature. The samples from later periods provided patterns typical
      for M. tuberculosis. This study clearly demonstrates that spoligotyping can be
      applied to historic tissue samples. In addition, our results do not support the
      theory that M. tuberculosis originated from the M. bovis type but, rather,
      suggest that human M. tuberculosis may have originated from a precursor complex
      probably related to M. africanum.

PMID- 12517875
TI  - M protein gene type distribution among group A streptococcal clinical isolates
      recovered in Mexico City, Mexico, from 1991 to 2000, and Durango, Mexico, from
      1998 to 1999: overlap with type distribution within the United States.
AB  - To examine the type distribution of pathogenic group A streptococcal (GAS)
      strains in Mexico, we determined the emm types of 423 GAS isolates collected from
      ill patients residing in Mexico (Durango or Mexico City). These included 282
      throat isolates and 107 isolates from normally sterile sites. Of the other
      isolates, 38 were recovered from other miscellaneous infections. A total of 31
      different emm types were found, revealing a broad overlap between commonly
      occurring emm types in Mexico and the United States. The information obtained in
      this study is consistent with the possibility that multivalent, M type-specific
      vaccines prepared for GAS strain distribution within the United States could
      theoretically protect against the majority of GAS strains causing disease in the
      two cities surveyed in Mexico.

PMID- 12517876
TI  - Detection of North American eastern and western equine encephalitis viruses by
      nucleic acid amplification assays.
AB  - We have developed nucleic acid sequence-based amplification (NASBA), standard
      reverse transcription PCR (RT-PCR), and TaqMan nucleic acid amplification assays
      for the rapid detection of North American eastern equine encephalitis (EEE) and
      western equine encephalitis (WEE) viral RNAs from samples collected in the field
      and clinical samples. The sensitivities of these assays have been compared to
      that of virus isolation. While all three types of nucleic acid amplification
      assays provide rapid detection of viral RNAs comparable to the isolation of
      viruses in Vero cells, the TaqMan assays for North American EEE and WEE viral
      RNAs are the most sensitive. We have shown these assays to be specific for North
      American EEE and WEE viral RNAs by testing geographically and temporally distinct
      strains of EEE and WEE viruses along with a battery of related and unrelated
      arthropodborne viruses. In addition, all three types of nucleic acid
      amplification assays have been used to detect North American EEE and WEE viral
      RNAs from mosquito and vertebrate tissue samples. The sensitivity, specificity,
      and rapidity of nucleic acid amplification demonstrate the usefulness of NASBA,
      standard RT-PCR, and TaqMan assays, in both research and diagnostic settings, to
      detect North American EEE and WEE viral RNAs.

PMID- 12517877
TI  - Stability of serotypes during nasopharyngeal carriage of Streptococcus
      pneumoniae.
AB  - Serotype changes among natural isolates of Streptococcus pneumoniae are well
      documented and occur by recombinational exchanges at the capsular biosynthetic
      locus. However, the frequency with which this phenomenon occurs within the
      nasopharynx of children is not clear and is likely to be highest in the
      nasopharynx of children, who have high rates of pneumococcal carriage. A birth
      cohort of 100 infants was studied, and pneumococci were recovered from
      nasopharyngeal samples taken at monthly intervals during the first 6 months of
      life and then at 2-monthly intervals until the age of 2 years. Among the 1,353
      nasopharyngeal samples were 523 that contained presumptive pneumococci, and three
      colonies from each were serotyped. A total of 333 isolates, including all
      isolates of differing serotypes from the same child, were characterized by
      multilocus sequence typing. Sixty-eight children carried multiple serotypes
      during the first 2 years of life. Two children carried a typeable and a
      nonserotypeable pneumococcus of identical genotype, and five children carried
      genetically indistinguishable isolates of serotypes 15B and 15C. These isolates
      were considered, respectively, to be due to loss of capsule expression and the
      known ability of serotype 15B and 15C pneumococci to interconvert by loss or gain
      of an acetyl group on the capsular polysaccharide. In all other cases, isolates
      from the same children that differed in serotype also differed in genotype,
      indicating the acquisition of a different pneumococcal strain rather than a
      change in capsular type. There was therefore no evidence in this study for any
      change of serotype due to recombinational replacements at the capsular locus
      among the pneumococci carried within the nasopharynges of the children.

PMID- 12517878
TI  - Identification of Haemophilus influenzae serotypes by standard slide
      agglutination serotyping and PCR-based capsule typing.
AB  - To resolve discrepancies in slide agglutination serotyping (SAST) results from
      state health departments and the Centers for Disease Control and Prevention
      (CDC), we characterized 141 of 751 invasive Haemophilus influenzae isolates that
      were identified in the United States from January 1998 to December 1999 through
      an active, laboratory-based, surveillance program coordinated by the CDC. We
      found discrepancies between the results of SAST performed at state health
      departments and those of PCR capsule typing performed at the CDC for 56 (40%) of
      the isolates characterized: 54 isolates that were identified as a particular
      serotype by SAST were shown to be unencapsulated by PCR, and two isolates that
      were reported as serotypes b and f were found to be serotypes f and e,
      respectively, by PCR. The laboratory error most likely to affect the perceived
      efficacy of the conjugate H. influenzae type b (Hib) vaccine was the
      misidentification of isolates as serotype b: of 40 isolates identified as
      serotype b by SAST, 27 (68%) did not contain the correlating capsule type genes.
      The frequency of errors fell substantially when standardized reagents and routine
      quality control of SAST were used during a study involving three laboratories. An
      overall 94% agreement between SAST and PCR results showed that slide
      agglutination could be a valid and reliable method for serotyping H. influenzae
      if the test was performed correctly, in accordance with standardized and
      recommended procedures. An ongoing prospective analysis of all H. influenzae
      surveillance isolates associated with invasive disease in children less than 5
      years old will provide more accurate national figures for the burden of invasive
      disease caused by Hib and other H. influenzae serotypes.

PMID- 12517879
TI  - Real-time PCR assay for rapid and accurate detection of point mutations
      conferring resistance to clarithromycin in Helicobacter pylori.
AB  - The main cause of failure of Helicobacter pylori eradication therapy is
      resistance to clarithromycin. The resistance is due to three point mutations in
      two positions on the 23S rRNA (A2142C, A2142G, and A2143G). Our aim was to
      develop a rapid and accurate method to detect these mutations directly on biopsy
      specimens. We developed a real-time PCR that included a simultaneous detection of
      the amplicons by hybridization of two probes labeled with LC-Red and fluorescein
      by using the fluorescence resonance energy transfer (FRET) technology and melting
      curve analysis with the LightCycler thermocycler. The assay was first applied
      successfully on reference strains, reference plasmids, and H. pylori-negative
      biopsies. Biopsies from 200 patients having failed a first eradication attempt
      and for whom the H. pylori strain was available were then tested with the new
      assay. A result was obtained in 199 cases; a single genotype was detected in 157
      cases, two genotypes were detected in 41 cases, and three genotypes were detected
      in one case. There were, in total, seven discrepancies between the real-time PCR
      and the phenotypic method of determination of clarithromycin susceptibility, and
      in an additional four cases the two phenotypic methods were in disagreement. PCR
      restriction fragment length polymorphism was applied to a sampling of biopsies,
      including all of the cases with multiple genotypes and all the cases with
      discrepant results. Finally, in four cases with discrepant results, the real-time
      PCR detected the resistant population at a concentration so low that it could not
      be detected by the phenotypic method, while in three cases other mutations could
      be involved. This assay had an accuracy at least as satisfactory as that of the
      phenotypic tests and could be performed within 2 h, allowing it to be used before
      the administration of therapy in the case of a first H. pylori eradication.

PMID- 12517880
TI  - Evaluation of broth microdilution testing parameters and agar diffusion Etest
      procedure for testing susceptibilities of Aspergillus spp. to caspofungin acetate
      (MK-0991).
AB  - The NCCLS M38-A document does not describe guidelines for testing caspofungin
      acetate (MK-0991) and other echinocandins against molds. This study evaluated the
      susceptibilities of 200 isolates of Aspergillus fumigatus, A. flavus, A.
      nidulans, A. niger, and A. terreus to caspofungin (MICs and minimum effective
      concentrations [MECs]) by using standard RPMI 1640 (RPMI) and antibiotic medium 3
      (M3), two inoculum sizes (10(3) and 10(4) CFU/ml), and two MIC determination
      criteria (complete [MICs-0] and prominent growth inhibition [MICs-2]) at 24 and
      48 h. Etest MICs were also determined. In general, caspofungin MIC-2 and MEC
      pairs were comparable with both media and inocula (geometric mean ranges of MECs
      and MICs, respectively, with larger inoculum: 0.12 to 0.64 microg/ml and 0.12 to
      0.44 microg/ml with RPMI versus 0.04 to 0.51 microg/ml and 0.03 to 0.21 microg/ml
      with M3); however, MEC results were less influenced by testing conditions than
      MICs, especially with the larger inoculum. Overall, the agreement between
      caspofungin Etest MICs and broth dilution values was higher with MECs obtained
      with M3 (>90%) and the large inoculum than under the other testing conditions.
      Because RPMI is a more stable and chemically defined medium than M3, the
      determination at 24 h of the easier visual MECs with RPMI and the inoculum
      recommended in the M38-A document appears to be a suitable procedure at present
      for in vitro testing of caspofungin against Aspergillus spp. Future in vitro
      correlations with in vivo outcome of both microdilution and Etest procedures may
      detect more-relevant testing conditions.

PMID- 12517881
TI  - Thymidine-dependent small-colony variants of Staphylococcus aureus exhibit gross
      morphological and ultrastructural changes consistent with impaired cell
      separation.
AB  - Thymidine-dependent small-colony variants (SCV) of Staphylococcus aureus
      exhibited unusual colony morphology with "fried-egg" or pinpoint white colonies
      on agar plates and pleomorphic cocci as determined by Gram staining. Electron
      microscopy revealed enlarged cocci with incomplete or multiple cross walls
      consistent with impaired cell separation. Fried-egg SCV phenotypes could be
      reversed by thymidine supplementation.

PMID- 12517882
TI  - Identification of Candida spp. by randomly amplified polymorphic DNA analysis and
      differentiation between Candida albicans and Candida dubliniensis by direct PCR
      methods.
AB  - Because Candida species have innately highly variable antifungal
      susceptibilities, the availability of a fast and reliable species identification
      test is very important so that suitable and effective therapeutic measures may be
      taken. Using three oligonucleotide primers, we established a randomly amplified
      polymorphic DNA (RAPD) analysis method that enabled direct identification of the
      most common opportunistic pathogenic Candida species. RAPD analysis revealed a
      characteristic molecular fingerprint for each Candida species. Differences
      between the profiles for Candida albicans and C. dubliniensis were evident. RAPD
      analysis is a relatively easy, reproducible, and reliable technique that can be
      useful in providing genetic fingerprints for the identification of strains. In
      addition, a collection of different C. albicans strains was identified by a
      specific PCR based on multiple secreted aspartic proteinase (SAP) genes and the
      dipeptidyl aminopeptidase (DAP2) gene. Our findings demonstrate that PCR based
      upon the SAP and DAP2 sequences is a simple, rapid, clear, and direct technique
      for the identification and differentiation of C. albicans and C. dubliniensis.

PMID- 12517883
TI  - Changes in patterns of antimicrobial susceptibility and integron carriage among
      Shigella sonnei isolates from southwestern Korea during epidemic periods.
AB  - Shigella sonnei isolates from southwestern Korea during the epidemic periods of
      1998 to 2000 were genetically related. The antimicrobial susceptibilities of the
      outbreak-related isolates changed annually. All isolates carried class 2
      integrons, and the outbreak-related isolates from 1999 also carried class 1
      integrons. The antimicrobial susceptibilities of S. sonnei isolates are readily
      changed by antibiotic selective pressures, and integrons are responsible for
      resistance to antimicrobial agents commonly used to treat shigellosis.

PMID- 12517884
TI  - Detection of Borrelia lonestari, putative agent of southern tick-associated rash
      illness, in white-tailed deer (Odocoileus virginianus) from the southeastern
      United States.
AB  - To determine if white-tailed deer may serve as a reservoir host for Borrelia
      lonestari, we used a nested PCR for the Borrelia flagellin gene to evaluate blood
      samples collected from deer from eight southeastern states. Seven of 80 deer
      (8.7%) from 5 of 17 sites (29.4%) had sequence-confirmed evidence of a B.
      lonestari flagellin gene by PCR, indicating that deer are infected with B.
      lonestari or another closely related Borrelia species. Our findings expand the
      known geographic range of B. lonestari and provide the first evidence of this
      organism in a vertebrate other than humans.

PMID- 12517885
TI  - Phenotypes and genotypes of erythromycin-resistant pneumococci in Italy.
AB  - Of 120 erythromycin-resistant pneumococci isolated in Italian hospitals, 39
      (32.5%) were M-type isolates, carrying the mef gene alone. The mef gene was also
      detected, together with erm(AM), in one constitutively resistant isolate and in
      five isolates of the partially inducible phenotype. Among the 45 mef-positive
      isolates, 25 (55.6%) carried mef(A) and 20 (44.4%) carried mef(E) as observed
      from PCR-restriction fragment length polymorphism analysis of a 1,743-bp
      amplicon. The same result was obtained by a similar method applied to a more
      common 348-bp amplicon.

PMID- 12517886
TI  - Antigen detection assay for identification of Penicillium marneffei infection.
AB  - Two recently produced monoclonal antibodies were used to develop an antigen
      capture enzyme-linked immunosorbent assay (ELISA) for rapid diagnosis of
      Penicillium marneffei. The method was evaluated with 53 patients with culture
      confirmed penicilliosis and 240 controls. The diagnostic sensitivity,
      specificity, and accuracy of the ELISA were 92.45, 97.5, and 96.59%,
      respectively.

PMID- 12517888
TI  - Use of real-time PCR to detect and quantify Mycoplasma haemofelis and "Candidatus
      Mycoplasma haemominutum" DNA.
AB  - A real-time PCR assay using Taqman probes was developed to detect and quantify
      Mycoplasma haemofelis and "Candidatus Mycoplasma haemominutum" in feline blood
      samples. The assay was rapid and sensitive and was successfully used to monitor
      the in vivo kinetics of cats experimentally infected with each species.

PMID- 12517887
TI  - Determination of immunoglobulin A against Gardnerella vaginalis hemolysin,
      sialidase, and prolidase activities in vaginal fluid: implications for adverse
      pregnancy outcomes.
AB  - A nested case-control study of low birth weight and preterm delivery was
      performed with singleton women. Immunoglobulin A (IgA) against the Gardnerella
      vaginalis hemolysin (anti-Gvh IgA) and sialidase and prolidase activities were
      determined in vaginal fluid at 17 weeks of gestation. Sialidase positivity and
      bacterial vaginosis with high prolidase activity were associated with 2- and 11
      fold increased risks for low birth weight, respectively. No woman with bacterial
      vaginosis plus a strong anti-Gvh IgA response had an adverse outcome.

PMID- 12517889
TI  - Sequence polymorphism of the 16S rRNA gene of Vibrio vulnificus is a possible
      indicator of strain virulence.
AB  - Vibrio vulnificus exhibits considerable strain-to-strain variation in virulence.
      Attempts to associate phenotypic or genotypic characteristics with strain
      virulence have been largely unsuccessful. Based on a 17-nucleotide difference
      throughout the sequence of the small subunit 16S rRNA gene, there are two major
      groups of V. vulnificus designated types A and B. In a survey of the 16S rRNA
      genotype in 67 V. vulnificus human clinical and nonclinical strains, we
      determined that the majority of nonclinical isolates are type A (31 of 33) and
      that there is a statistically significant association between the type B genotype
      and human clinical strains (26 of 34).

PMID- 12517890
TI  - Accuracy of a commercial enzyme-linked immunosorbent assay for CagA in patients
      from Brazil with and without gastric carcinoma.
AB  - We validated a commercial enzyme-linked immunosorbent assay for the detection of
      anti-CagA antibodies in Brazilian patients with Helicobacter pylori infection.
      The test presented high sensitivity (97.4%) and specificity (88.9%) when employed
      in patients without gastric carcinoma. However, in gastric carcinoma patients,
      the test was neither sensitive nor specific enough to detect cagA-positive H.
      pylori infection.

PMID- 12517891
TI  - Comparison of washing and swabbing procedures for collecting genital fluids to
      assess shedding of human immunodeficiency virus type 1 (HIV-1) RNA in
      asymptomatic HIV-1-infected women.
AB  - Human immunodeficiency virus type 1 (HIV-1) RNA was detected by means of
      ultrasensitive reverse transcription-PCR assay of 19 cervicovaginal lavage, 21
      cervical mucus, 18 vaginal wall, and 17 vaginal fornix paired samples from 25
      asymptomatic HIV-1-infected women (76, 84, 72, and 68%, respectively; P > 0.5).
      Levels of HIV-1 RNA in cervicovaginal wash samples were highly correlated with
      those in paired endocervical mucus samples (r = 0.71; P = 0.0006), indicating
      that cervicovaginal washing and endocervical swabbing are equivalent collection
      procedures.

PMID- 12517892
TI  - Identification of Balamuthia mandrillaris by PCR assay using the mitochondrial
      16S rRNA gene as a target.
AB  - Balamuthia mandrillaris is an opportunistic pathogen that causes granulomatous
      amebic meningoencephalitis in animals, including humans. Based on sequence
      analysis of mitochondrial small-subunit-rRNA genes, we developed primers that
      amplify a Balamuthia-specific PCR product. These primers will be useful for
      retrospective analyses of fixed tissues and possible identification of Balamuthia
      in vivo.

PMID- 12517893
TI  - Prevalence of agr specificity groups among Staphylococcus aureus strains
      colonizing children and their guardians.
AB  - PCR-based assays were used to evaluate agr locus nucleotide polymorphism for the
      identification of agr autoinducer receptor specificity groups within a population
      of Staphylococcus aureus isolates colonizing children and their guardians. All
      isolates could be assigned to one of three major agr groups that had similar
      prevalences, regardless of whether isolates were implicated in transmission of S.
      aureus within families. Among healthy carriers, agr groups I to III appear to be
      equally fit, which may reflect selection for the coexistence of S. aureus strains
      in a population.

PMID- 12517894
TI  - Characterization of the first extended-spectrum beta-lactamase-producing
      Salmonella isolate identified in Canada.
AB  - A single Salmonella enterica serovar Typhimurium isolate with an UT2 phage type
      producing an extended-spectrum beta-lactamase (ESBL) was identified in Canada in
      2000. The isolate harbored two plasmids, one containing a bla(TEM-1) gene and the
      other containing a bla(SHV-2a) gene. The ESBL gene was located on a 70-kb
      transferable plasmid which also carried tetracycline and trimethoprim resistance
      elements.

PMID- 12517895
TI  - Epidemiology and antimicrobial susceptibilities of 111 Campylobacter fetus subsp.
      fetus strains isolated in Quebec, Canada, from 1983 to 2000.
AB  - The epidemiology and antimicrobial susceptibilities of 111 Campylobacter fetus
      subsp. fetus strains isolated from 103 patients from 1983 to 2000 in Quebec,
      Canada, were determined. The median number of patients infected annually with
      this bacteria was seven, with an incidence of 0.1 per 100,000 population. The
      male-to-female ratio was 1.1 to 1.0. The patients originated from 13 of the 18
      Quebec socioeconomic regions. The age range of the patients was 6 months to 90
      years old, 53% being > or = 70 years old and 2% being <20 years old. The
      isolation site was blood for 69% of the patients, stools for 20%, and other body
      fluids for 11% of them. Three patients suffered a relapse, with the same strain
      being isolated from the same site at different times as confirmed by pulse-field
      gel electrophoresis. All isolates were susceptible to ampicillin, gentamicin,
      meropenem, and imipenem, with 90% minimal inhibitory concentrations of 4, 1,
      0.12, and < or = 0.06 microg/ml, respectively. Three percent and two percent of
      the strains were, respectively, resistant and intermediate to ciprofloxacin.
      Thirty-four percent of the strains were resistant to tetracycline. There was a
      nonsignificant increase in resistance to ciprofloxacin (P = 0.27) and to
      tetracycline (P = 0.65) in recent years. The percentages of intermediate and
      resistant MICs were, respectively, 12 and 1% for cefotaxime and 71 and 0% for
      erythromycin. All strains were beta-lactamase negative.

PMID- 12517896
TI  - Evaluation of new medium for identification of dermatophytes and primary
      dimorphic pathogens.
AB  - Only 25 of 77 dermatophytic isolates caused dermatophyte identification medium
      (DIM) to turn purple after incubation at the recommended temperature (37 degrees
      C); the accuracy of the results was improved at 30 degrees C (71 of 77 isolates
      yielded positive results). Many dimorphic pathogenic fungi also tested positive
      at both incubation temperatures. Thus, DIM has limited usefulness for presumptive
      identification of dermatophytes.

PMID- 12517897
TI  - Processing sputum specimens in a refrigerated centrifuge does not increase the
      rate of isolation of Mycobacterium tuberculosis.
AB  - A total of 1,047 sputum samples from pulmonary tuberculosis patients was
      collected in cetyl pyridinium chloride-sodium chloride solution. Each sample was
      divided into two parts and randomly allocated for the isolation of Mycobacterium
      tuberculosis, with one part to be processed by the standard method and the other
      by a modified method. In the standard method, the samples were processed by using
      nonrefrigerated centrifuges, while in the modified method, they were processed by
      using a refrigerated centrifuge. Fifty-seven samples that yielded contaminants
      were excluded, and the remaining 990 samples were taken up for analysis. The
      rates of isolation of M. tuberculosis with the standard and modified methods were
      48.6 and 48.1%, respectively, and the difference was not statistically
      significant (McNemar's test; P > 0.5). However, 51% of the positive cultures were
      isolated within 2 weeks with the modified method compared to 37% with the
      standard method (chi-square test; P < 0.001). The results of the study reveal
      that processing of sputum samples in a refrigerated centrifuge does not improve
      the rate of isolation but will result in rapid isolation of M. tuberculosis.

PMID- 12517898
TI  - Prevalence of Candida species, including Candida dubliniensis, in Singapore.
AB  - We present data on the prevalence of Candida species isolated from inpatients in
      three Singapore hospitals and from vaginal samples collected at community
      clinics. Strikingly, approximately 20% of the isolates from blood and vaginal
      samples were fluconazole-resistant species. By analyzing species-specific gene
      sequence signatures, we identified Candida dubliniensis from both groups of
      patients.

PMID- 12517899
TI  - Detecting Candida albicans in human milk.
AB  - Procedures for diagnosis of mammary candidosis, including laboratory
      confirmation, are not well defined. Lactoferrin present in human milk can inhibit
      growth of Candida albicans, thereby limiting the ability to detect yeast
      infections. The inhibitory effect of various lactoferrin concentrations on the
      growth of C. albicans in whole human milk was studied. The addition of iron to
      the milk led to a two- to threefold increase in cell counts when milk contained
      3.0 mg of lactoferrin/ml and markedly reduced the likelihood of false-negative
      culture results. This method may provide the necessary objective support needed
      for diagnosis of mammary candidosis.

PMID- 12517900
TI  - Trichosporon loubieri infection in a patient with adult polycystic kidney
      disease.
AB  - A 45-year-old man from Nepal with a 13-year history of polycystic kidney disease
      was diagnosed as suffering from chronic renal failure with end-stage renal
      disease. After receiving empirical antituberculosis treatment, he was treated
      with broad-spectrum antibiotics. A left nephrectomy was performed, and after 4
      months, he received a kidney transplant. The left kidney was grossly enlarged,
      with multiple cystic spaces filled with blackish material. Histologic examination
      of the excised left kidney tissue stained with hematoxylin and eosin and Gomori's
      methenamine silver stains showed numerous hyaline, septate, fungal hyphae of
      various lengths, many broken into rectangular arthroconidia in the cystic spaces.
      Culture of the kidney tissue yielded white, glabrous, yeast-like colonies. Based
      on its micromorphology, growth at 42 degrees C, and ribosomal DNA (rDNA) sequence
      analysis, and also sequence analysis of the internal-transcribed-spacer and D1/D2
      rDNA regions, the yeast was identified as Trichosporon loubieri. Postsurgically,
      the patient was treated with amphotericin B and oral itraconazole, followed by
      maintenance therapy with fluconazole. He remained afebrile and asymptomatic. At
      the final follow-up, all parameters were found normal and the patient was doing
      well, with normal renal function reports. This paper presents the first known
      case of human infection caused by T. loubieri.

PMID- 12517901
TI  - Antimicrobial activities against 84 Listeria monocytogenes isolates from patients
      with systemic listeriosis at a comprehensive cancer center (1955-1997).
AB  - Listeriosis is a serious complication in patients undergoing treatment for
      cancer. We present antimicrobial susceptibility profiles of 84 clinical Listeria
      monocytogenes isolates. During 1955 to 1997, in vitro susceptibility for
      penicillin (97.6%), ampicillin (90.7%), erythromycin (98.8%), tetracycline
      (96.9%), and gentamicin (98.0%) remained unchanged. All isolates were susceptible
      to amikacin, ciprofloxacin, imipenem, rifampin, trimethoprim-sulfamethoxazole
      (TMP-SMX), and vancomycin. High prevalence of clindamycin resistance (96.2%) was
      unexpected. Ampicillin plus gentamicin is standard therapy for systemic
      listerosis, and TMP-SMX may be used for patients with beta-lactam intolerance. In
      vitro susceptibility profiles for carbapenem and fluoronated quinolone are
      promising, although clinical validation is critically needed before routine use
      is advocated, especially for listeric patients with severe cellular immune
      defects.

PMID- 12517902
TI  - Clarithromycin resistance among Helicobacter pylori strains isolated from
      children: prevalence and study of mechanism of resistance by PCR-restriction
      fragment length polymorphism analysis.
AB  - Clarithromycin and metronidazole resistance was 29.1 and 23.9%, respectively, in
      96 Helicobacter pylori strains obtained from pediatric patients. No resistance to
      amoxicillin was observed. Resistance according to patients' ages to
      clarithromycin and metronidazole was 45.4 and 18.2% in 22 patients from 4 to 8
      years old, 30.2 and 20.7% in 53 patients from 9 to 13 years old, and 9.5 and
      38.1% in 21 patients from 14 to 18 years old, respectively. The A2143G mutation
      was the most prevalent (82.1%) among clarithromycin-resistant strains.

PMID- 12517903
TI  - Evaluation of a method for identification of Candida dubliniensis bloodstream
      isolates.
AB  - To evaluate methods for differentiating Candida albicans and Candida
      dubliniensis, 772 putative C. albicans bloodstream isolates were tested for
      growth at 37 and 42 degrees C. Isolates showing no growth at 42 degrees C,
      abundant chlamydospore production, and the sugar assimilation pattern of the type
      strain were confirmed by DNA-based procedures to be C. dubliniensis.

PMID- 12517904
TI  - Evaluation of MicroScan Autoscan for identification of Pseudomonas aeruginosa
      isolates from cystic fibrosis patients.
AB  - Accurate identification of gram-negative bacilli from cystic fibrosis (CF)
      patients is essential. Only 57% (108 of 189) of nonmucoid strains and 40% (24 of
      60) of mucoid strains were definitively identified as Pseudomonas aeruginosa with
      MicroScan Autoscan. Most common misidentifications were Pseudomonas fluorescens
      Pseudomonas putida (i.e., the strain was either P. fluorescens or P. putida, but
      the system did not make the distinction and yielded the result P.
      fluorescens/putida) and Alcaligenes spp. Extending the incubation to 48 h
      improved identification, but 15% of isolates remained misidentified. The
      MicroScan Autoscan system cannot be recommended for the identification of P.
      aeruginosa isolates from CF patients.

PMID- 12517905
TI  - Detection and treatment of bloodstream infection: laboratory reporting and
      antimicrobial management.
AB  - We analyzed antimicrobial use in 509 episodes of clinically significant
      bloodstream infection to assess the impact that microbiology laboratory reporting
      had on antimicrobial management. Most therapy interventions occurred at the time
      of phlebotomy and after notification of Gram stain results by telephone. Release
      of antimicrobial susceptibility data had the least impact on antimicrobial
      management.

PMID- 12517906
TI  - Analysis of Mycobacterium avium complex isolates from blood samples of AIDS
      patients by pulsed-field gel electrophoresis.
AB  - A molecular analysis of the first Mycobacterium avium complex (MAC) blood
      isolates from 177 patients from 10 Canadian cities revealed that each cluster of
      indistinguishable strains consisted of isolates from epidemiologically unrelated
      patients in the same city or region. This study supports the premise that
      acquisition of MAC from a common environmental source occasionally occurs.

PMID- 12517907
TI  - Rapid detection of classical swine fever virus by a portable real-time reverse
      transcriptase PCR assay.
AB  - A fluorogenic-probe hydrolysis (TaqMan)-reverse transcriptase PCR assay for
      classical swine fever virus (CSFV) was developed and evaluated in experimentally
      infected swine. The assay detected CSFV, representing different phylogenetic
      groupings, but did not amplify viral RNA from related pestiviruses. The assay met
      or exceeded the sensitivity (1 to 100 50% tissue culture infective doses per ml)
      of viral cultures of samples from experimentally infected animals. Viral RNA was
      detected in nasal and tonsil scraping samples 2 to 4 days prior to the onset of
      clinical disease. The assay can be performed in 2 h or less, thus providing a
      rapid method for the diagnosis of classical swine fever.

PMID- 12517908
TI  - Uses and limitations of the XTT assay in studies of Candida growth and
      metabolism.
AB  - Colorimetric tetrazolium assays are used increasingly in studies of fungi, often
      in the absence of standardization or correlation with other methods. We examined
      species- and strain-related tetrazolium metabolism in Candida albicans and
      Candida parapsilosis by using XTT [2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5
      [(phenylamino) carbonyl]-2H-tetrazolium hydroxide] and WST-8 [2-(2-methoxy-4
      nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium] and found
      marked variations. Also, significant signal was often missed in the absence of
      dimethyl sulfoxide extraction.

PMID- 12517909
TI  - Clostridium difficile brain empyema after prolonged intestinal carriage.
AB  - Clostridium difficile, the most common cause of antibiotic-associated diarrhea,
      is occasionally isolated from extraintestinal sites and is usually found as part
      of a polymicrobial flora. We report a case of brain empyema that occurred after
      the recurrent intestinal carriage of a nontoxigenic strain of C. difficile. Brain
      abscess cultures contained both toxigenic and nontoxigenic isolates. Pulsed-field
      gel electrophoresis showed that nontoxigenic isolates from the intestine and from
      the brain were identical.

PMID- 12517910
TI  - Meningitis due to mixed infection with penicillin-resistant and penicillin
      susceptible strains of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is the major cause of bacterial meningitis. We report a
      case of meningitis due to a mixed infection with two distinct strains of S.
      pneumoniae: one penicillin-resistant strain of serotype 9V and one penicillin
      susceptible strain of serotype 7. The two strains exhibited different pulsed
      field gel electrophoresis profiles.

PMID- 12517911
TI  - Acute Mycoplasma pneumoniae infection presenting as cholestatic hepatitis.

PMID- 12517912
TI  - Introduction of human immunodeficiency virus type 2 infection in the Philippines.
AB  - The aim of this study was to describe and document the first case of human
      immunodeficiency virus type 2 (HIV-2) in the Philippines by using serological and
      molecular techniques and to compare the diversity of this strain to that of
      strains from other countries. With the introduction of HIV-2 into the country and
      the presence of diversified strains of HIV-1, the use of highly sensitive assays
      to detect all these strains is recommended.

PMID- 12517913
TI  - Staphylococcus lugdunensis carrying the mecA gene causes catheter-associated
      bloodstream infection in premature neonate.
AB  - A premature neonate had a catheter-associated bloodstream infection due to
      Staphylococcus lugdunensis. The MIC of oxacillin for the strain was >256
      microg/ml, and the mecA gene of S. lugdunensis was detected by PCR. The infection
      was resolved after removal of the line and treatment with vancomycin for 2 weeks.

PMID- 12517914
TI  - Culture-negative childhood empyema is usually due to penicillin-sensitive
      Streptococcus pneumoniae capsular serotype 1.

PMID- 12517916
TI  - Searching for Bacillus anthracis in suspect powders: a French experience.

PMID- 12517915
TI  - Comment on "Acute echinococcosis: a case report".

PMID- 12517920
TI  - Inhibition of tumor necrosis factor alpha-mediated NFkappaB activation and
      leukocyte adhesion, with enhanced endothelial apoptosis, by G protein-linked
      receptor (TP) ligands.
AB  - Tumor necrosis factor (TNF) alpha is a critical mediator of inflammation;
      however, TNFalpha is rarely released alone and the "cross-talk" between different
      classes of inflammatory mediators is largely unexplored. Thromboxane A(2)
      (TXA(2)) is released during I/R injury and exerts its effects via a G protein
      linked receptor (TP). In this study, we found that TXA(2) mimetics stimulate
      leukocyte adhesion molecule (LAM) expression on endothelium via TPbeta. The
      potential interaction between TXA(2) and TNFalpha in altering endothelial
      survival and LAM expression was examined. IBOP, a TXA(2) mimetic, attenuated
      TNFalpha-induced LAM expression in vitro, in a concentration-dependent manner, by
      preventing TNFalpha-enhanced gene expression, and also reduced TNFalpha-induced
      leukocyte adhesion to endothelium both in vitro and in vivo. IBOP abrogated
      TNFalpha-induced NFkappaB activation in endothelial cells, as determined by
      reduced IkappaB phosphorylation and NFkappaB nuclear translocation, by inhibiting
      the assembly of signaling intermediates with the intracellular domain of TNF
      receptors 1 and 2 in response to TNFalpha. This inhibition resulted from the
      Galpha(q)-mediated enhancement of STAT1 activation and was reversed by anti-STAT1
      antisense oligonucleotides. TNFalpha-mediated TNFR1-FADD association and caspase
      8 activation were not inhibited by IBOP co-stimulation, however, resulting in a
      2.6-fold increase in endothelial cell apoptosis. By stimulating the vessel wall
      and inducing endothelial cell apoptosis, TXA(2), in combination with TNFalpha,
      may hamper the angiogenic response during inflammation or ischemia, thus reducing
      revascularization and tissue viability.

PMID- 12517926
TI  - Cutting edge: proliferating fibroblasts respond to collagenous C1q with
      phosphorylation of p38 mitogen-activated protein kinase and apoptotic features.
AB  - Interactions of C1q collagen tails with human fibroblasts induce G(1) mitotic
      arrest. The hypothesis tested in this study is that the antiproliferative effect
      of C1q tails is mediated through activation of stress responsive pathway(s). Upon
      C1q treatment, proliferating fibroblasts were examined by immunoblotting with a
      panel of Abs to the mitogen-activated protein kinase (MAPK) superfamily. The
      cells selectively increased phosphorylation of p38 MAPK, upstream dual activator
      MAPK kinase 3/6, and downstream transcription factors activating transcription
      factor 2, ETS domain transcription factor 1, and C/EBP homologous protein in a
      time-dependent manner. Phosphorylations were mediated, in part, by ligation of
      surface C1q tail-binding calreticulin. These events correlated with the
      appearance of apoptotic nuclei and DNA fragmentation in the cultures, which
      increased with a time response curve. The apoptotic features were linked to p38
      activities because the selective inhibitor SB203580 prevented both
      phosphorylation of the pathway and DNA fragmentation. Hence, p38 activation might
      provide a molecular basis for linking mitotic arrest and apoptosis of fibroblasts
      by C1q tails.

PMID- 12517927
TI  - Cutting edge: homeostatic proliferation of peripheral T lymphocytes is regulated
      by clonal competition.
AB  - Homeostatic proliferation functions to maintain peripheral T cell numbers and is
      regulated by cytokines. In this study, we provide evidence that T cell
      homeostasis is also regulated by clonal competition. Naive polyclonal T cells
      divided when transferred to TCR transgenic hosts, as did monoclonal T cells when
      transferred to TCR transgenic hosts of differing clonotype. However, T cells did
      not divide in hosts of identical clono-type. Transgenic T cell proliferation was
      inhibited in irradiated hosts of the same clonotype, while cotransferred
      nontransgenic T cells proliferated extensively. These results show that clonal
      competition is a component of homeostasis that may contribute to selection of the
      peripheral T cell repertoire.

PMID- 12517928
TI  - Inhibition of metalloproteinase cleavage enhances the cytotoxicity of Fas ligand.
AB  - The Fas ligand (FasL)/Fas receptor (CD95) pathway is an important mediator of
      apoptosis in the immune system and can also mediate cancer cell death. Soluble
      FasL (sFasL), shed from the membrane-bound form of the molecule by a putative
      metalloproteinase (MP), may function to locally regulate the activity of membrane
      bound FasL. Using a replication-defective recombinant adenovirus-expressing FasL
      (RAdFasL), we identified a variable ability of different carcinoma cells to
      respond to FasL-induced cytotoxicity and to shed sFasL. Blockade of FasL cleavage
      with an MP inhibitor significantly enhanced RAdFasL-induced apoptosis suggesting
      that sFasL may antagonize the effect of membrane-bound FasL. In support of this
      concept, a recombinant adenovirus expressing a noncleavable form of FasL (RAdD4)
      was found to be a potent inducer of apoptosis even at very low virus doses. Our
      results highlight the therapeutic potential of noncleavable FasL as an antitumor
      agent and emphasize the important role of MP via the production of sFasL in
      regulating the response of the Fas pathway. Moreover, these findings have general
      implications for the therapeutic exploitation of TNF family ligands and for the
      possible impact of MP-based therapies on the normal physiology of Fas/TNF
      pathways.

PMID- 12517929
TI  - Intrinsic differences in the proliferation of naive and memory human B cells as a
      mechanism for enhanced secondary immune responses.
AB  - Humoral immune responses elicited after secondary exposure to immunizing Ag are
      characterized by robust and elevated reactivity of memory B cells that exceed
      those of naive B cells during the primary response. The mechanism underlying this
      difference in responsiveness of naive vs memory B cells remains unclear. We have
      quantitated the response of naive and memory human B cells after in vitro
      stimulation with T cell-derived stimuli. In response to stimulation with CD40
      ligand alone or with IL-10, both IgM-expressing and Ig isotype-switched memory B
      cells entered their first division 20-30 h earlier than did naive B cells. In
      contrast, the time spent traversing subsequent divisions was similar. Consistent
      with previous studies, only memory cells differentiated to CD38(+) blasts in a
      manner that increased with consecutive division number. These differentiated
      CD38(+) B cells divided faster than did CD38(-) memory B cell blasts.
      Proliferation of CD40 ligand-stimulated naive B cells as well as both CD38(+) and
      CD38(-) cells present in cultures of memory B cells was increased by IL-10. In
      contrast, IL-2 enhanced proliferation of CD38(-) and CD38(+) memory B cell
      blasts, but not naive cells. Thus, memory B cells possess an intrinsic advantage
      over naive B cells in both the time to initiate a response and in the division
      based rate of effector cell development. These differences help explain the
      accelerated Ab response exhibited by memory B cells after secondary challenge by
      an invading pathogen, a hallmark of immunological memory.

PMID- 12517930
TI  - Hypoxia regulates expression and activity of Kv1.3 channels in T lymphocytes: a
      possible role in T cell proliferation.
AB  - T lymphocytes are exposed to hypoxia during their development and also when they
      migrate to hypoxic pathological sites such as tumors and wounds. Although hypoxia
      can affect T cell development and function, the mechanisms by which immune cells
      sense and respond to changes in O(2)-availability are poorly understood. K(+)
      channels encoded by the Kv1.3 subtype of the voltage-dependent Kv1 gene family
      are highly expressed in lymphocytes and are involved in the control of membrane
      potential and cell function. In this study, we investigate the sensitivity of
      Kv1.3 channels to hypoxia in freshly isolated human T lymphocytes and leukemic
      Jurkat T cells. Acute exposure to hypoxia (20 mmHg, 2 min) inhibits Kv1.3
      currents in both cell types by 20%. Prolonged exposure to hypoxia (1% O(2) for 24
      h) selectively decreases Kv1.3 protein levels in Jurkat T cells by 47%, but not
      Kvbeta2 and SK2 Ca-activated K(+) channel subunit levels. The decrease in Kv1.3
      protein levels occurs with no change in Kv1.3 mRNA expression and is associated
      with a significant decrease in K(+) current density. A decrease in Kv1.3
      polypeptide levels similar to that obtained during hypoxia is produced by Kv1.3
      channel blockage. Our results indicate that hypoxia produces acute and long-term
      inhibition of Kv1.3 channels in T lymphocytes. This effect could account for the
      inhibition of lymphocyte proliferation during hypoxia. Indeed, we herein present
      evidence showing that hypoxia selectively inhibits TCR-mediated proliferation and
      that this inhibition is associated with a decrease in Kv1.3 proteins.

PMID- 12517931
TI  - Impaired lymphopoiesis and altered B cell subpopulations in mice overexpressing
      Lnk adaptor protein.
AB  - Lnk is an adaptor protein expressed primarily in lymphocytes and hemopoietic
      precursor cells. Marked expansion of B lineage cells occurs in lnk(-/-) mice,
      indicating that Lnk regulates B cell production by negatively controlling pro-B
      cell expansion. In addition, lnk(-/-) hemopoietic precursors have an advantage in
      repopulating the hemopoietic system of irradiated host animals. In this study, we
      show that Lnk overexpression results in impaired expansion of lymphoid precursor
      cells and altered mature B cell subpopulations. The representation of both B
      lineage and T lineage cells was reduced in transgenic mice overexpressing Lnk
      under the control of a lymphocyte-specific expression vector. Whereas the overall
      number of B and T cells was correlated with Lnk protein expression levels,
      marginal zone B cells in spleen and B1 cells in the peritoneal cavity were
      relatively resistant to Lnk overexpression. The C-terminal tyrosine residue,
      conserved among Lnk family adaptor proteins, was dispensable for the negative
      regulatory roles of Lnk in lymphocyte development. Our results illuminate the
      novel negative regulatory mechanism mediated by the Lnk adaptor protein in
      controlling lymphocyte production and function.

PMID- 12517933
TI  - Decreased E12 and/or E47 transcription factor activity in the bone marrow as well
      as in the spleen of aged mice.
AB  - The E2A-encoded transcription factors E12 and E47 are key regulators of B cell
      functions. They bind to the E-box site, found in regulatory regions of B cell
      specific genes; promote cell survival of early pre-B cells; help to initiate Ig
      rearrangements; and are also involved in class switch in mature B cells in the
      periphery. We have investigated the expression and function of E47 and E12 in IL
      7-expanded pro-B/pre-B cell precursors and in unstimulated or LPS-activated
      splenic B cells from young and old BALB/c mice. Results show that B cell
      precursors from the bone marrow of old mice exhibit a reduced expression of E2A
      proteins and a reduced ability to bind DNA, as compared with young mice. In the
      spleen, E2A protein expression and DNA binding are present in unstimulated B
      cells from young mice and, to a significantly lesser extent, from old mice. These
      are both strongly induced by activation in splenic B cells from young mice but
      only moderately induced in old mice, indicating that aging affects the expression
      and activity of E2A-encoded genes and also that DNA binding correlates with the
      amount of protein expression. The levels of E2A DNA binding in the spleen
      correlate with those in the bone marrow for individual mice. In splenic mature B
      cells, only E47/E47 complexes bind DNA; whereas in bone marrow B cell precursors,
      E47/E12 complexes participate in DNA binding. Only nuclear extracts of splenic
      mature B cells, but both nuclear and cytoplasmic extracts of bone marrow B cell
      precursors, exhibit DNA binding.

PMID- 12517932
TI  - Program death-1 engagement upon TCR activation has distinct effects on
      costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and
      IL-21, but not CD28, IL-7, and IL-15 responses.
AB  - The program death 1 (PD-1) receptor and its ligands, PD-1 ligand (PD-L)1 and PD
      L2, define a novel regulatory pathway with potential inhibitory effects on T, B,
      and monocyte responses. In the present study, we show that human CD4(+) T cells
      express PD-1, PD-L1, and PD-L2 upon activation, and Abs to the receptor can be
      agonists or antagonists of the pathway. Under optimal conditions of stimulation,
      ICOS but not CD28 costimulation can be prevented by PD-1 engagement. IL-2 levels
      induced by costimulation are critical in determining the outcome of the PD-1
      engagement. Thus, low to marginal IL-2 levels produced upon ICOS costimulation
      account for the greater sensitivity of this pathway to PD-1-mediated inhibition.
      Interestingly, exogenous IL-2, IL-7, and IL-15 but not IL-4 and IL-21 can rescue
      PD-1 inhibition, suggesting that among these cytokines only those that activate
      STAT5 can rescue PD-1 inhibition. As STAT5 has been implicated in the maintenance
      of IL-2Ralpha expression, these results suggest that IL-7 and IL-15 restore
      proliferation under conditions of PD-1 engagement by enhancing high-affinity IL
      2R expression and hence, IL-2 responsiveness.

PMID- 12517934
TI  - CD154 plays a central role in regulating dendritic cell activation during
      infections that induce Th1 or Th2 responses.
AB  - We compared splenic DC activation during infection with either the Th2 response
      inducing parasite Schistosoma mansoni or with the Th1 response-inducing parasite
      Toxoplasma gondii. CD8alpha(+) DC from schistosome-infected mice exhibited a 2-
      to 3-fold increase in the expression of MHC class II, CD80, and CD40 (but not
      CD86) compared with DC from uninfected control animals, while CD8alpha(-) DC
      exhibited a 2- to 3-fold increase in the expression of MHC class II and CD80 and
      no alteration, compared with DC from uninfected mice, in the expression of CD86
      or CD40. Intracellular staining revealed that DC did not produce IL-12 during
      infection with S. mansoni. In contrast, infection with T. gondii resulted in a
      more pronounced increase in the expression of activation-associated molecules
      (MHC class II, CD80, CD86, and CD40) on both CD8alpha(-) and CD8alpha(+) splenic
      DC and promoted elevated IL-12 production by DC. Analysis of MHC class I and of
      additional costimulatory molecules (ICOSL, ICAM-1, OX40L, 4-1BBL, and B7-DC)
      revealed a generally similar pattern, with greater indication of activation in T.
      gondii-infected mice compared with S. mansoni-infected animals. Strikingly, the
      activation of DC observed during infection with either parasite was not apparent
      in DC from infected CD154(-/-) mice, indicating that CD40/CD154 interactions are
      essential for maintaining DC activation during infection regardless of whether
      the outcome is a Th1 or a Th2 response. However, the ability of this activation
      pathway to induce IL-12 production by DC is restrained in S. mansoni-infected,
      but not T. gondii-infected, mice by Ag-responsive CD11c(-) cells.

PMID- 12517935
TI  - Either IL-2 or IL-12 is sufficient to direct Th1 differentiation by nonobese
      diabetic T cells.
AB  - Th cell differentiation from naive precursors is a tightly controlled process;
      the most critical differentiation factor is the action of the driving cytokine:
      IL-12 for Th1 development, IL-4 for Th2 development. We found that CD4(+) T cells
      from nonobese diabetic mice spontaneously differentiate into IFN-gamma-producing
      Th1 cells in response to polyclonal TCR stimulation in the absence of IL-12 and
      IFN-gamma. Instead, IL-2 was necessary and sufficient to direct T cell
      differentiation to the Th1 lineage by nonobese diabetic CD4(+) T cells. Its
      ability to direct Th1 differentiation of both naive and memory CD4(+) T cells was
      clearly uncoupled from its ability to stimulate cell division. Autocrine IL-2
      driven Th1 differentiation of nonobese diabetic T cells may represent a genetic
      liability that favors development of IFN-gamma-producing autoreactive T cells.

PMID- 12517936
TI  - CD4+ T cells from lupus-prone mice avoid antigen-specific tolerance induction in
      vivo.
AB  - Activated T cells in spontaneous lupus presumably bypass normal tolerance
      mechanisms in the periphery, since thymic tolerance appears intact. To determine
      whether such T cells indeed avoid in vivo peripheral tolerance mechanisms, we
      assessed their activation and recall responses after in vivo Ag stimulation in
      the absence of exogenously supplied costimulatory signals. Naive CD4(+) AND
      (transgenic mice bearing rearranged TCR specific for pigeon cytochrome c,
      peptides 88-104) TCR-transgenic T cells, specific for pigeon cytochrome c, from
      lupus-prone Fas-intact MRL/Mp+(Fas-lpr) and from H-2(k)-matched control CBA/CaJ
      and B10.BR mice (MRL.AND, CBA.AND, and B10.AND, respectively) were adoptively
      transferred into (MRL x CBA)F(1) or (MRL x B10)F(1) recipients transgenically
      expressing membrane-bound pigeon cytochrome c as a self-Ag. MRL.AND and control
      CBA.AND and B10.AND-transgenic T cells were activated and divided after transfer,
      indicating encounter with their cognate Ag; however, T cells from CBA.AND and
      B10.AND mice were impaired in their ability to proliferate and produce IL-2 after
      challenge with pigeon cytochrome c in ex vivo recall assays, a typical phenotype
      of anergized cells. By contrast, MRL.AND T cells proliferated more, and a
      significantly higher percentage of such cells produced IL-2, compared with
      control T cells. This observation that MRL T cells avoided anergy induction in
      vivo was confirmed in an in vitro system where the cells were stimulated with an
      anti-CD3 in the absence of a costimulatory signal. These experiments provide
      direct evidence that CD4(+) T cells from Fas-intact lupus-prone MRL mice are more
      resistant than nonautoimmune control cells to anergy induction. Anergy avoidance
      in the periphery might contribute to the characteristic finding in lupus of
      inappropriate T cell activation in response to ubiquitous self-Ags.

PMID- 12517937
TI  - Down-modulation of responses to type I IFN upon T cell activation.
AB  - The immunomodulatory role of type I IFNs (IFN-alpha/beta) in shaping T cell
      responses has been demonstrated, but the direct effects of IFN on T cells are
      still poorly characterized. Particularly, because IFN exert an antiproliferative
      activity, it remains elusive how the clonal expansion of effector T cells can
      paradoxically occur in the event of an infection when large amounts of IFN are
      produced. To address this issue, we have studied the effects of type I IFN in an
      in vitro differentiation model of human primary CD4(+) T cells. We found that IFN
      alpha treatment of resting naive T cells delayed their entry into the cell cycle
      after TCR triggering. Conversely, the ongoing expansion of effector T cells was
      not inhibited by the presence of IFN. Moreover, activated T cells showed a
      significantly reduced induction of IFN-sensitive genes, as compared with naive
      precursors, and this decline occurred independently of subset-specific
      polarization. The residual type I IFN response measured in activated T cells was
      found sufficient to inhibit replication of the vesicular stomatitis virus. Our
      data suggest that the activation of T lymphocytes includes regulatory processes
      that restrain the transcriptional response to IFN and allow the proliferation of
      effector cells in the presence of this cytokine.

PMID- 12517938
TI  - Mechanisms of enhanced macrophage-mediated prostaglandin E2 production and its
      suppressive role in Th1 activation in Th2-dominant BALB/c mice.
AB  - PGE(2) has been known to suppress Th1 responses. We studied the difference in
      strains of mice in PGE(2) production by macrophages and its relation to Th1
      activation. Macrophages from BALB/c mice produced greater amounts of PGE(2) than
      those from any other strains of mice, including C57BL/6, after LPS stimulation.
      In accordance with the amount of PGE(2) produced, macrophage-derived IL-12 and T
      cell-derived IFN-gamma production were more strongly suppressed in BALB/c
      macrophages than in C57BL/6 macrophages. When macrophages were treated with
      indomethacin or EP4 antagonist, Th1 cytokines were more markedly increased in
      cells from BALB/c mice than in those from C57BL/6 mice. Although cyclooxygenase-2
      was expressed similarly after LPS stimulation in these mouse strains, the release
      of arachidonic acid and the expression of type V secretory phospholipase A(2)
      mRNA were greater in BALB/c macrophages. However, exogenous addition of
      arachidonic acid did not reverse the lower production of PGE(2) by C57BL/6
      macrophages. The expression of microsomal PGE synthase, a final enzyme of PGE(2)
      synthesis, was also greater in BALB/c macrophages. These results indicate that
      the greater production of PGE(2) by macrophages, which is regulated by secretory
      phospholipase A(2) and microsomal PGE synthase but not by cyclooxygenase-2, is
      related to the suppression of Th1 cytokine production in BALB/c mice.

PMID- 12517939
TI  - Protection against experimental autoimmune encephalomyelitis generated by a
      recombinant adenovirus vector expressing the V beta 8.2 TCR is disrupted by
      coadministration with vectors expressing either IL-4 or -10.
AB  - Adenovirus vectors are increasingly being used for genetic vaccination and may
      prove highly suitable for intervention in different pathological conditions due
      to their capacity to generate high level, transient gene expression. In this
      study, we report the use of a recombinant adenovirus vector to induce regulatory
      responses for the prevention of autoimmune diseases through transient expression
      of a TCR beta-chain. Immunization of B10.PL mice with a recombinant adenovirus
      expressing the TCR Vbeta8.2 chain (Ad5E1 mVbeta8.2), resulted in induction of
      regulatory type 1 CD4 T cells, directed against the framework region 3
      determinant within the B5 peptide (aa 76-101) of the Vbeta8.2 chain. This
      determinant is readily processed and displayed in an I-A(u) context, on ambient
      APC. Transient genetic delivery of the TCR Vbeta8.2 chain protected mice from Ag
      induced experimental autoimmune encephalomyelitis. However, when the Ad5E1
      mVbeta8.2 vector was coadministered with either an IL-4- or IL-10-expressing
      vector, regulation was disrupted and disease was exacerbated. These results
      highlight the importance of the Th1-like cytokine requirement necessary for the
      generation and activity of effective regulatory T cells in this model of
      experimental autoimmune encephalomyelitis.

PMID- 12517940
TI  - Long term maintenance of IgE-mediated memory in mast cells in the absence of
      detectable serum IgE.
AB  - Mast cells and basophils involved in allergic responses do not have clonotypic Ag
      receptors. However, they can acquire Ag specificity through binding of Ag
      specific IgE to FcepsilonRI expressed on their surface. Previous studies
      demonstrated that IgE binding induced the stabilization and accumulation of
      FcepsilonRI on the cell surface and resulted in up-regulation of FcepsilonRI. In
      this study we have further analyzed the maintenance of IgE-mediated memory in
      mast cells and basophils in vivo by comparing kinetics of serum IgE levels,
      FcepsilonRI expression, and ability to induce systemic anaphylaxis. A single i.v.
      injection of trinitrophenyl-specific IgE induced 8-fold up-regulation of
      FcepsilonRI expression on peritoneal mast cells in B cell-deficient (micro m(-/
      )) mice. Serum IgE levels became undetectable by day 6, but the treatment of mice
      with anti-IgE mAb induced a significant drop in body temperature on days 14, 28,
      and 42. The administration of trinitrophenyl -BSA, but not BSA, in place of anti
      IgE mAb gave similar results, indicating the Ag specificity of the allergic
      response. This long term maintenance of Ag-specific reactivity in the allergic
      response was also observed in normal mice passively sensitized with IgE even
      though the duration was shorter than that in B cell-deficient mice. The
      appearance of IgE with a different specificity did not interfere with the
      maintenance of IgE-mediated memory of mast cells and basophils. These results
      suggest that IgE-mediated stabilization and up-regulation of FcepsilonRI enables
      mast cells and basophils not only to acquire Ag specificity, but also to maintain
      memory in vivo for lengthy periods of time.

PMID- 12517941
TI  - Differential requirements for expression of CD80/86 and CD40 on B cells for T
      dependent antibody responses in vivo.
AB  - The CD80/86-CD28 and CD40-CD40 ligand costimulatory pathways are essential for Th
      cell-dependent B cell responses that generate high-affinity, class-switched Ab in
      vivo. Disruption of either costimulatory pathway results in defective in vivo
      humoral immune responses, but it remains unclear to what extent this is due to
      deficient activation of Th cells and/or of B cells. To address this issue, we
      generated mixed chimeras in which CD80/86- or CD40-deficient bone marrow-derived
      cells coexist with wild-type (WT) cells, thereby providing the functional T cell
      help and accessory cell functions required for fully competent B cell responses.
      We were then able to assess the requirement for CD80/86 or CD40 expression on B
      cells producing class-switched Ig in response to a T-dependent Ag. In CD80/86 WT
      plus CD80/86 double-knockout mixed chimeras, both WT- and CD80/86-deficient B
      cells produced IgG1 and IgE responses, indicating that direct signaling by
      CD80/86 is not essential for efficient B cell activation. In marked contrast,
      only WT IgG1 and IgE responses were detected in the chimeras containing CD40
      deficient cells, demonstrating that CD40 expression on B cells is essential for
      class switching by those B cells. Thus, while disrupting either the CD80/86-CD28
      or the CD40-CD40 ligand costimulatory pathway abrogates T-dependent B cell immune
      responses, the two pathways are nonredundant and mediated by distinct mechanisms.

PMID- 12517942
TI  - Complement component 3 is required for optimal expansion of CD8 T cells during a
      systemic viral infection.
AB  - In addition to its established role in innate immune mechanisms, complement
      component C3 is also of critical importance in B cell activation and T cell
      dependent Ab responses. In this study, we have examined the requirement for C3 in
      the generation of primary CD8 T cell responses to an acute systemic viral
      infection. We compared Ag-specific CD8 T cell responses to lymphocytic
      choriomeningitis virus (LCMV) between wild-type (+/+) and C3-deficient (C3(-/-))
      mice on both 129/B6 and B6 backgrounds. These studies revealed that C3 activity
      is required for optimal expansion of LCMV-specific effector CD8 T cells in an
      epitope-dependent fashion, which is influenced by the genetic background of the
      mice. Studies in complement receptor 1/2 (CR1/CR2)-deficient mice showed that
      regulation of LCMV-specific CD8 T cell responses by C3 is not dependent upon
      CR1/CR2. These findings may have implications in vaccine development, therapy of
      autoimmune diseases, and prevention of graft rejection.

PMID- 12517943
TI  - Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell
      adhesion and invasion through a beta 1 integrin-dependent mechanism.
AB  - Beta(1) integrins play a crucial role in supporting tumor cell attachment to and
      invasion into the extracellular matrix. Endotoxin/LPS introduced by surgery has
      been shown to enhance tumor metastasis in a murine model. Here we show the direct
      effect of LPS on tumor cell adhesion and invasion in extracellular matrix
      proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor
      cell lines SW480 and SW620 constitutively expressed high levels of the beta(1)
      subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6)
      expression were detected. SW480 and SW620 did not express membrane-bound CD14;
      however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated
      beta(1) integrin expression; enhanced tumor cell attachment to fibronectin,
      collagen I, and laminin; and strongly promoted tumor cell invasion through the
      Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14
      induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with
      sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition
      of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of
      beta(1) integrin expression and prevented tumor cell adhesion and invasion. These
      results provide direct evidence that although SW480 and SW620 cells do not
      express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB,
      up-regulate beta(1) integrin expression, and subsequently promote tumor cell
      adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and
      invasion through extracellular matrix proteins is beta(1) subunit-dependent.

PMID- 12517944
TI  - The intracellular granzyme B inhibitor, proteinase inhibitor 9, is up-regulated
      during accessory cell maturation and effector cell degranulation, and its
      overexpression enhances CTL potency.
AB  - Granzyme B (grB) is a serine proteinase released by cytotoxic lymphocytes (CLs)
      to kill abnormal cells. GrB-mediated apoptotic pathways are conserved in
      nucleated cells; hence, CLs require mechanisms to protect against ectopic or
      misdirected grB. The nucleocytoplasmic serpin, proteinase inhibitor 9 (PI-9), is
      a potent inhibitor of grB that protects cells from grB-mediated apoptosis in
      model systems. Here we show that PI-9 is present in CD4(+) cells, CD8(+) T cells,
      NK cells, and at lower levels in B cells and myeloid cells. PI-9 is up-regulated
      in response to grB production and degranulation, and associates with grB
      containing granules in activated CTLs and NK cells. Intracellular complexes of PI
      9 and grB are evident in NK cells, and overexpression of PI-9 enhances CTL
      potency, suggesting that cytoplasmic grB, which may threaten CL viability, is
      rapidly inactivated by PI-9. Because dendritic cells (DCs) acquire
      characteristics similar to those of target cells to activate naive CD8(+) T cells
      and therefore may also require protection against grB, we investigated the
      expression of PI-9 in DCs. PI-9 is evident in thymic DCs (CD3(-), CD4(+), CD8(-),
      CD45(+)), tonsillar DCs, and DC subsets purified from peripheral blood (CD16(+)
      monocytes and CD123(+) plasmacytoid DCs). Furthermore, PI-9 is expressed in
      monocyte-derived DCs and is up-regulated upon TNF-alpha-induced maturation of
      monocyte-derived DCs. In conclusion, the presence and subcellular localization of
      PI-9 in leukocytes and DCs are consistent with a protective role against ectopic
      or misdirected grB during an immune response.

PMID- 12517945
TI  - Microbial colonization drives lymphocyte accumulation and differentiation in the
      follicle-associated epithelium of Peyer's patches.
AB  - Peyer's patches (PPs) are lined by follicle-associated epithelium (FAE) with Ag
      transporting M cells. To investigate the spatial relationships of B cells, T
      cells, and dendritic cells (DCs) in PPs during microbial colonization, their in
      situ redistribution was examined in germfree (GF) rats exposed to a conventional
      pathogen-free microflora (conventionalized, CV). Although occasional B and T
      cells occurred in the FAE of GF rats, it contained mainly immature DCs
      (CD4(+)CD86(-)), whereas mature DCs (CD86(high)) were seen in the interfollicular
      zones even under GF conditions. In CV rats, DCs had disappeared from the FAE,
      which instead contained clusters by B and T cells associated with induction of
      putative M cell pockets. CD86 was seen neither in the FAE nor in the follicles
      under GF conditions, but it became apparent on intraepithelial B cells 5 wk after
      colonization. The level of CD86 on these B cells was comparable to that on
      germinal center B cells, although the B cell follicles did not show direct
      contact with the M cell areas. B cells in the follicular mantles acquired Bcl-2
      after 12 wk in CV rats, whereas B cells in the FAE did not express Bcl-2 at a
      substantial level throughout the experimental period. The cellular redistribution
      patterns and phenotypic characteristics observed after colonization suggested
      that immature DCs, but not B cells, are involved in Ag presentation during
      primary immune responses against intestinal bacteria. However, the spatial
      cellular relationships sequentially being established among DCs, B cells, and T
      cells in PPs, are most likely important for the induction of post-germinal center
      B cells subsequently residing within the M cell pockets.

PMID- 12517946
TI  - Indoleamine 2,3-dioxygenase is regulated by IFN-gamma in the mouse placenta
      during Listeria monocytogenes infection.
AB  - The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is expressed
      in macrophages that have been differentiated in the presence of CSF-1 and is
      important in the containment of intracellular pathogens. IDO also appears to play
      a role in suppression of T cell responses in a variety of contexts. In the
      placenta, its enzymatic activity is believed to establish a chemical barrier that
      protects the fetal allograft from T cell-mediated immune aggression. We have
      studied the regulation of IDO in the utero-placental unit of mice following
      infection with the Gram-positive, intracellular bacterium Listeria monocytogenes
      that has a predilection for replication in the decidua basalis. IDO mRNA and
      protein expression is enhanced in the utero-placental unit following infection
      with L. monocytogenes. However, in contrast to the human where IDO is expressed
      by the CSF-1R-positive syncytial trophoblast, IDO is not expressed in murine
      trophoblastic tissue but instead is found in stromal cells of the decidua basalis
      and metrial gland and following infection, in endothelial cells. Using mice
      carrying null mutations in cytokine/growth factor genes, we explored the
      regulation of IDO in the placenta. Consistent with the absence of CSF-1R
      expression in the IDO-expressing cells of mice, neither the basal levels of IDO
      nor its induction following infection is affected by the absence of CSF-1.
      However, although the basal level of IDO is normal, the enhanced expression
      during Listeriosis is completely abrogated in the absence of IFN-gamma, a
      cytokine required for the resolution of this infection. These data suggest that
      IDO plays a role in resolving bacterial infection in the placenta while at the
      same time maintaining a barrier to T cells whose presence might result in fetal
      rejection.

PMID- 12517947
TI  - Nonmyelin-specific T cells accelerate development of central nervous system APC
      and increase susceptibility to experimental autoimmune encephalomyelitis.
AB  - Previously we demonstrated that both myelin-specific and nonmyelin-specific rat T
      cells were capable of accelerating the development of transplanted rat BM-derived
      APC in the CNS of SCID C.B-17/scid (SCID) mice. This suggested that nonmyelin
      specific T cells might be capable of increasing susceptibility to EAE by
      increasing the number and function of APC in the CNS before disease induction. To
      assess this possibility, we evaluated disease incidence, day of onset, duration,
      mean peak severity, cumulative disease index, and histopathology in the presence
      or absence of nonmyelin-specific T cells. The results demonstrate an association
      between T cell responses to nonmyelin Ags, accelerated development of BM-derived
      CNS APC before disease induction, and heightened susceptibility to CNS
      inflammation mediated by myelin-specific T cells. This suggests that T cell
      responses to nonmyelin Ags can potentiate CNS inflammation by elevating the
      functional presence of CNS APC.

PMID- 12517948
TI  - IL-6 and matrix metalloproteinase-1 are regulated by the cyclin-dependent kinase
      inhibitor p21 in synovial fibroblasts.
AB  - During the pathogenesis of rheumatoid arthritis (RA), the synovial fibroblasts
      increase in number and produce proinflammatory cytokines and matrix
      metalloproteinases (MMPs) that function to promote inflammation and joint
      destruction. Recent investigations have suggested that cell cycle activity and
      inflammation may be linked. However, little is known about the mechanisms
      responsible for the coordinate regulation of proliferation and the expression of
      proinflammatory molecules in RA synovial fibroblasts. Here, we demonstrate a 50
      +/- 10% decrease in the expression of p21, a cell cycle inhibitor, in the
      synovial fibroblast population from RA compared with osteoarthritis (OA) synovial
      tissue. Moreover, p21 positivity in the synovial fibroblasts inversely correlates
      with medium synovial lining thickness (r = -0.76; p < 0.02). The expression of
      p21 is also reduced in isolated RA synovial fibroblasts compared with OA synovial
      fibroblasts. Adenovirus-mediated delivery of p21 (Ad-p21) arrests both RA and OA
      synovial fibroblasts in the G(0)/G(1) phase of the cell cycle without inducing
      cytotoxicity. However, the spontaneous production of IL-6 and MMP-1 is suppressed
      only in the Ad-p21-infected RA synovial fibroblasts, indicating a novel role for
      p21 in RA. Analyses of p21-deficient mouse synovial fibroblasts reveal a 100-fold
      increase in IL-6 protein and enhance IL-6 and MMP-3 mRNA. Restoration of p21, but
      not overexpression of Rb, which also induces G(0)/G(1) cell cycle arrest,
      decreases IL-6 synthesis in p21-null synovial fibroblasts. Furthermore, in RA
      synovial fibroblasts the ectopic expression of p21 reduces activation of the AP-1
      transcription factor. Additionally, p21-null synovial fibroblasts display
      enhanced activation of AP-1 compared with wild-type synovial fibroblasts. These
      data suggest that alterations in p21 expression may activate AP-1 leading to
      enhanced proinflammatory cytokine and MMP production and development of
      autoimmune disease.

PMID- 12517949
TI  - A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen
      presentation and induction of dendritic cell maturation.
AB  - Dendritic cells (DCs) are the only APCs capable of initiating adaptive immune
      responses. The initiation of immune responses requires that DCs 1) internalize
      and present Ags; and 2) undergo a differentiation process, called "maturation",
      which transforms DCs into efficient APCs. DC maturation may be initiated by the
      engagement of different surface receptors, including certain cytokine receptors
      (such as TNFR), Toll-like receptors, CD40, and FcRs. The early activation events
      that link receptor engagement and DC maturation are not well characterized. We
      found that FcR engagement by immune complexes induced the phosphorylation of Syk,
      a protein tyrosine kinase acting immediately downstream of FcRs. Syk was
      dispensable for DC differentiation in vitro and in vivo, but was strictly
      required for immune complexes internalization and subsequent Ag presentation to T
      lymphocytes. Importantly, Syk was also required for the induction of DC
      maturation and IL-12 production after FcR engagement, but not after engagement of
      other surface receptors, such as TNFR or Toll-like receptors. Therefore, protein
      tyrosine phosphorylation by Syk represents a novel pathway for the induction of
      DC maturation.

PMID- 12517950
TI  - IFN-gamma production is specifically regulated by IL-10 in mice made tolerant
      with anti-CD40 ligand antibody and intact active bone.
AB  - We have developed a strategy to induce tolerance to allografts, involving
      cotransplantation of allogeneic intact active bone and transient anti-CD40 ligand
      mAb therapy. Tolerance induced by this approach in C57BL/6 mice receiving BALB/c
      hearts is not mediated by deletional mechanisms, but by peripheral regulatory
      mechanisms. Tolerance is associated with diminished ex vivo IFN-gamma production
      that is donor specific, and a reduction in the frequency of IFN-gamma-producing
      cells. Splenocytes from mice tolerant to BALB/c grafts, but sensitized to third
      party C3H skin grafts, demonstrated normally primed ex vivo IFN-gamma responses
      to C3H stimulators. Neutralizing anti-IL-10 and anti-IL-10R, but not anti-TGF
      beta, anti-IL-4, or anti-CTLA-4, Abs restored the ex vivo IFN-gamma response to
      BALB/c stimulators. There was no significant difference in IL-2 or IL-4
      production between tolerant and rejecting mice, and anti-IL-10 mAbs had no effect
      on IL-2 or IL-4 production. The Cincinnati cytokine capture assay was used to
      test whether suppression of IFN-gamma production in vivo was also a marker of
      tolerance. In naive mice, we observed a dramatic increase in serum IFN-gamma
      levels following challenge with allogeneic BALB/c splenocytes or hearts. Tolerant
      mice challenged with allogeneic BALB/c splenocytes or hearts made significantly
      less or undetectable amounts of IFN-gamma. No IL-4 or IL-10 production was
      detected in tolerant or rejecting mice. Collectively, our studies suggest that
      active suppression of IFN-gamma production by IL-10 is correlated with, and may
      contribute to, tolerance induced with intact active bone and anti-CD40 ligand
      mAbs.

PMID- 12517951
TI  - A thyroid tumor-specific antigen formed by the fusion of two self proteins.
AB  - Thyroid epithelial cells frequently express one or more members of the rearranged
      during transfection/papillary thyroid carcinoma (RET/PTC) fusion oncogene family
      during early stages of cancer, and fusion gene transcripts have been found in
      inflammatory conditions of the thyroid such as the autoimmune disease,
      Hashimoto's thyroiditis. Because these oncogenes encode chimeric proteins, novel
      RET/PTC epitopes may be targets of antitumor immune responses. We have been
      interested in the RET/PTC3 (RP3) fusion protein because this family member is
      more frequently expressed in radiation-induced and childhood papillary carcinomas
      than other members of the fusion oncogene family. We hypothesized that the
      activated kinase of c-RET, in the form of RP3, when expressed in patients with
      thyroid disease, presents an unusual altered self target for T cell recognition.
      Interestingly, we find that immunization with mouse RP3 protein can induce a
      strongly immunogenic response to RP3, although this response is not directed
      against the peptide comprising the unique fusion region. Rather, the responses
      are specific for the carboxyl-terminal portion of RP3 that is derived from the
      self protein c-RET. Furthermore, transplantation of RP3-expressing thyroid tumors
      into naive mice resulted in leukocytic infiltration, tumor rejection, and
      induction of RP3-specific T cells. Thus, the somatic fusion of two unrelated self
      proteins results in the development of a uniquely immunogenic response directed
      against self epitopes within RP3. These studies may better define the mechanisms
      controlling the initiation of thyroid-specific immune responses and provide
      insight into the design of novel molecules for invoking tumor-specific immunity.

PMID- 12517952
TI  - Detection of autoreactive myelin proteolipid protein 139-151-specific T cells by
      using MHC II (IAs) tetramers.
AB  - Detection of autoreactive T cells using MHC II tetramers is difficult because of
      the low affinity of their TCR. We have generated a class II tetramer using the
      IA(s) class II molecule combined with an autoantigenic peptide from myelin
      proteolipid protein (PLP; PLP(139-151)) and used it to analyze myelin PLP(139
      151)-reactive T cells. Using monomers and multimerized complexes labeled with PE,
      we confirmed the specificity of the reagent by bioassay and flow cytometry. The
      IA(s) tetramers stimulated and stained the PLP(139-151)-specific 5B6 TCR
      transgenic T cells and a polyclonal cell line specific for PLP(139-151), but not
      a control T cell line specific for PLP(178-191). We used this reagent to optimize
      conditions to detect low affinity autoreactive T cells. We found that high pH (
      approximately 8.0) and neuraminidase treatment enhances the staining capacity of
      PLP(139-151) tetramer without compromising specificity. Furthermore, we found
      that induction of calcium fluxing by tetramers in T cells may be used as a
      sensitive measure to detect autoreactive T cells with a low affinity. Taken
      together, the data show that the tetrameric reagent binds and stimulates PLP(139
      151)-reactive T cells with specificity. This tetrameric reagent will be useful in
      studying the evolution of PLP(139-151)-specific repertoire in naive mice and its
      expansion during the autoimmune disease experimental autoimmune
      encephalomyelitis.

PMID- 12517953
TI  - Suppressor of cytokine signaling-1 has IFN-gamma-independent actions in T cell
      homeostasis.
AB  - Suppressor of cytokine signaling (SOCS)-1 is a member of a family of proteins
      that negatively regulate cytokine signaling pathways. We have previously
      established that SOCS-1 is a key regulator of IFN-gamma signaling and that IFN
      gamma is responsible for the complex inflammatory disease that leads to the death
      of SOCS-1-deficient mice. In this study, we provide evidence that SOCS-1 is also
      a critical regulator of IFN-gamma-independent immunoregulatory factors. Mice
      lacking both SOCS-1 and IFN-gamma, although outwardly healthy, have clear
      abnormalities in their immune system, including a reduced ratio of CD4:CD8 T
      cells in lymphoid tissues and increased expression of T cell activation markers.
      To examine the contribution of TCR Ag specificity to these immune defects, we
      have generated two lines of SOCS-1-deficient mice expressing a transgenic TCR
      specific for an exogenous Ag, OVA (OT-I and OT-II). Although TCR transgenic SOCS
      1(-/-) mice have a longer lifespan than nontransgenic SOCS-1(-/-) mice, they
      still die as young adults with inflammatory disease and the TCR transgenic SOCS
      1(-/-) T cells appear activated despite the absence of OVA. This suggests that
      both Ag-dependent and -independent mechanisms contribute to the disease in SOCS-1
      deficient mice. Thus, SOCS-1 is a critical regulator of T cell activation and
      homeostasis, and its influence extends beyond regulating IFN-gamma signaling.

PMID- 12517954
TI  - IL-4 induces apoptosis in A549 lung adenocarcinoma cells: evidence for the
      pivotal role of 15-hydroxyeicosatetraenoic acid binding to activated peroxisome
      proliferator-activated receptor gamma transcription factor.
AB  - The proinflammatory cytokine IL-4 is secreted in large amounts during allergic
      inflammatory response in asthma and plays a pivotal role in the airway
      inflammation. IL-4 has been shown to up-regulate 15-lipoxygenase and produce
      15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in A549 cells via the Janus
      kinase/STAT6 pathway under coactivation of CREB binding protein/p300. IL-4 has
      also been shown to up-regulate peroxisome proliferator-activated receptor gamma
      (PPARgamma) nuclear receptors in macrophages and A549 cells. In this study we
      demonstrate that 15(S)-HETE binds to PPARgamma nuclear receptors and induces
      apoptosis in A549 cells. Moreover, pretreatment of cells with
      nordihydroguaiaretic acid, a 15-lipoxygenase inhibitor, prevented PPARgamma
      activation and apoptosis. The latter was accomplished by the interaction of the
      15(S)-HETE/PPARgamma complex with the adapter protein Fas-associating protein
      with death domain and caspase-8, as shown by transfection of Fas-associating
      protein with death domain dominant negative vector and cleavage of caspase 8 to
      active subunits p41/42 and p18. Whereas IL-4 and PPARgamma ligands failed to
      induce cleavage of Bid and release of cytochrome c from mitochondria, they caused
      translocation of the proapoptotic protein Bax from cytoplasm to mitochondria with
      a concomitant decrease in the Bcl-x(L) level. We therefore believe that in
      unstimulated cells Bcl-x(L) and Bax form a heterodimer, in which Bcl-x(L)
      dominates and prevents the induction of apoptosis, whereas in IL-4-stimulated
      cells the 15(S)-HETE/PPARgamma complex down-regulates Bcl-x(L), and the resulting
      overweight of Bax commits the cell to apoptosis via caspase-3. However, this
      pathway does not rule out the direct caspase-8-mediated activation of caspase-3.
      In conclusion, IL-4-induced apoptosis may contribute to severe loss of alveolar
      structures and infiltration of eosinophils, mononuclear phagocytes, etc., into
      the lung tissue of chronic asthma patients.

PMID- 12517955
TI  - T cell chemokine receptor expression in aging.
AB  - Changes in chemokine receptor expression are important in determining T cell
      migration and the subsequent immune response. To better understand the
      contribution of the chemokine system in immune senescence we determined the
      effect of aging on CD4(+) T cell chemokine receptor function using microarray,
      RNase protection assays, Western blot, and in vitro chemokine transmigration
      assays. Freshly isolated CD4(+) cells from aged (20-22 mo) mice were found to
      express a higher level of CCR1, 2, 4, 5, 6, and 8 and CXCR2-5, and a lower level
      of CCR7 and 9 than those from young (3-4 mo) animals. Caloric restriction
      partially or completely restored the aging effects on CCR1, 7, and 8 and CXCR2,
      4, and 5. The aging-associated differences in chemokine receptor expression
      cannot be adequately explained by the age-associated shift in the naive/memory or
      Th1/Th2 profile. CD4(+) cells from aged animals have increased chemotactic
      response to stromal cell-derived factor-1 and macrophage-inflammatory protein
      1alpha, suggesting that the observed chemokine receptor changes have important
      functional consequences. We propose that the aging-associated changes in T cell
      chemokine receptor expression may contribute to the different clinical outcome in
      T cell chemokine receptor-dependent diseases in the elderly.

PMID- 12517956
TI  - Lipid raft-independent B cell receptor-mediated antigen internalization and
      intracellular trafficking.
AB  - The Ag-specific B cell receptor (BCR) expressed by B lymphocytes has two distinct
      functions upon interaction with cognate Ag: signal transduction (generation of
      intracellular second messenger molecules) and Ag internalization for subsequent
      processing and presentation. While it is known that plasma membrane domains,
      termed lipid rafts, are involved in BCR-mediated signal transduction, the precise
      role of plasma membrane lipid rafts in BCR-mediated Ag internalization and
      intracellular trafficking is presently unclear. Using a highly characterized
      model system, it was determined that while plasma membrane lipid rafts can be
      internalized by B lymphocytes, lipid rafts do not represent a major pathway for
      the rapid and efficient internalization of cell surface Ag-BCR complexes.
      Moreover, internalized plasma membrane lipid rafts are delivered to intracellular
      compartments distinct from those to which the bulk of internalized Ag-BCR
      complexes are delivered. These results demonstrate that B lymphocytes, like other
      cell types, possess at least two distinct endocytic pathways (i.e., clathrin
      coated pits and plasma membrane lipid rafts) that deliver internalized ligands to
      distinct intracellular compartments. Furthermore, Ag-BCR complexes differentially
      access these two distinct internalization pathways.

PMID- 12517957
TI  - Lipid raft distribution of CD4 depends on its palmitoylation and association with
      Lck, and evidence for CD4-induced lipid raft aggregation as an additional
      mechanism to enhance CD3 signaling.
AB  - By mutagenesis, we demonstrated that the palmitoylation of the membrane-proximal
      Cys(396) and Cys(399)of CD4, and the association of CD4 with Lck contribute to
      the enrichment of CD4 in lipid rafts. Ab cross-linking of CD4 induces an
      extensive membrane patching on the T cell surface, which is related to lipid raft
      aggregation. The lipid raft localization of CD4 is critical for CD4 to induce the
      aggregation of lipid rafts. The localization of CD4 in lipid rafts also
      correlates to the ability of CD4 to enhance receptor tyrosine phosphorylation.
      Thus, our data suggest that CD4-induced aggregation of lipid rafts may play an
      additional role in CD4 signaling besides its adhesion to MHC molecules and
      association with Lck.

PMID- 12517958
TI  - The GTP-binding domain of class II transactivator regulates its nuclear export.
AB  - The transcriptional coactivator class II transactivator (CIITA), although
      predominantly localized in the nucleus, is also present in the cytoplasm. The
      subcellular distribution of CIITA is actively regulated by the opposing actions
      of nuclear export and import. In this study, we show that nuclear export is
      negatively regulated by the GTP-binding domain (GBD; aa 421-561) of CIITA:
      mutation or deletion of the GBD markedly increased export of CIITA from the
      nucleus. Remarkably, a CIITA GBD mutant binds CRM1/exportin significantly better
      than does wild-type CIITA, leading to the conclusion that GTP is a negative
      regulator of CIITA nuclear export. We also report that, in addition to the
      previously characterized N- and C-terminal nuclear localization signal elements,
      there is an additional N-terminal nuclear localization activity, present between
      aa 209 and 222, which overlaps the proline/serine/threonine-rich domain of CIITA.
      Thus, fine-tuning of the nucleocytoplasmic distribution of coactivator proteins
      involved in transcription is an active and dynamic process that defines a novel
      mechanism for controlling gene regulation.

PMID- 12517959
TI  - Up-regulation of early growth response gene-1 via the CXCR3 receptor induces
      reactive oxygen species and inhibits Na+/K+-ATPase activity in an immortalized
      human proximal tubule cell line.
AB  - The CXCR3 chemokine receptor, a member of the CXCR family, has been linked to a
      pathological role in autoimmune disease, inflammatory disease, allograft
      rejection, and ischemia. In the kidney, expression of the CXCR3 receptor and its
      ligands is up-regulated in states of glomerulonephritis and in allograft
      rejection, but little is known about the expression and functional role the CXCR3
      receptor might play. Here, we study the function of the CXCR3 chemokine receptor
      in an immortalized human proximal tubular cell line (IHKE-1). Stimulation of the
      CXCR3 receptor by its selective agonist monokine induced by IFN-gamma leads via a
      Ca(2+)-dependent mechanism to an up-regulation of early growth response gene
      (EGR)-1. Overexpression of EGR-1 induces down-regulation of copper-zinc
      superoxide dismutase and manganese superoxide dismutase and stimulates the
      generation of reactive oxygen species (ROS) via the NADH/NADPH-oxidase system.
      EGR-1 overexpression or treatment with monokine induced by IFN-gamma resulted in
      a ROS-dependent inhibition of basolateral Na(+)/K(+)-ATPase activity,
      compromising sodium transport in these cells. Thus, activation of the CXCR3
      receptor in proximal tubular cells might disturb natriuresis during inflammatory
      and ischemic kidney disease via EGR-1-mediated imbalance of ROS.

PMID- 12517960
TI  - Impaired transporter associated with antigen processing (TAP) function
      attributable to a single amino acid alteration in the peptide TAP subunit TAP1.
AB  - The heterodimeric peptide transporter TAP belongs to the ABC transporter family.
      Sequence comparisons with the P-glycoprotein and cystic fibrosis transmembrane
      conductance regulator and the functional properties of selective amino acids in
      these ABC transporters postulated that the glutamic acid at position 263 and the
      phenylalanine at position 265 of the TAP1 subunit could affect peptide
      transporter function. To define the role of both amino acids, TAP1 mutants
      containing a deletion or a substitution to alanine at position 263 or 265 were
      generated and stably expressed in murine and human TAP1(-/-) cells. The different
      TAP1 mutants were characterized in terms of expression and function of TAP, MHC
      class I surface expression, immune recognition, and species-specific differences.
      The phenotype of murine and human cells expressing human TAP1 mutants with a
      deletion or substitution of Glu(263) was comparable to that of TAP1(-/-) cells.
      In contrast, murine and human TAP1 mutant cells containing a deletion or mutation
      of Phe(265) of the TAP1 subunit exhibit wild-type TAP function. This was
      associated with high levels of MHC class I surface expression and recognition by
      specific CTL, which was comparable to that of wild-type TAP1-transfected control
      cells. Thus, biochemical and functional evidence is presented that the Glu(263)
      of the TAP1 protein, but not the Phe(265), is critical for proper TAP function.

PMID- 12517961
TI  - Systematic analysis of the combinatorial nature of epitopes recognized by TCR
      leads to identification of mimicry epitopes for glutamic acid decarboxylase 65
      specific TCRs.
AB  - Accumulating evidence indicates that recognition by TCRs is far more degenerate
      than formerly presumed. Cross-recognition of microbial Ags by autoreactive T
      cells is implicated in the development of autoimmunity, and elucidating the
      recognition nature of TCRs has great significance for revelation of the disease
      process. A major drawback of currently used means, including positional scanning
      synthetic combinatorial peptide libraries, to analyze diversity of epitopes
      recognized by certain TCRs is that the systematic detection of cross-recognized
      epitopes considering the combinatorial effect of amino acids within the epitope
      is difficult. We devised a novel method to resolve this issue and used it to
      analyze cross-recognition profiles of two glutamic acid decarboxylase 65
      autoreactive CD4(+) T cell clones, established from type I diabetes patients. We
      generated a DNA-based randomized epitope library based on the original glutamic
      acid decarboxylase epitope using class II-associated invariant chain peptide
      substituted invariant chains. The epitope library was composed of seven
      sublibraries, in which three successive residues within the epitope were
      randomized simultaneously. Analysis of agonistic epitopes indicates that
      recognition by both TCRs was significantly affected by combinations of amino
      acids in the antigenic peptide, although the degree of combinatorial effect
      differed between the two TCRs. Protein database searching based on the TCR
      recognition profile proved successful in identifying several microbial and self
      protein-derived mimicry epitopes. Some of the identified mimicry epitopes were
      actually produced from recombinant microbial proteins by APCs to stimulate T cell
      clones. Our data demonstrate the importance of the combinatorial nature of amino
      acid residues of epitopes in molecular mimicry.

PMID- 12517962
TI  - A single polymorphic residue within the peptide-binding cleft of MHC class I
      molecules determines spectrum of tapasin dependence.
AB  - Different HLA class I alleles display a distinctive dependence on tapasin for
      surface expression and Ag presentation. In this study, we show that the tapasin
      dependence of HLA class I alleles correlates to the nature of the amino acid
      residues present at the naturally polymorphic position 114. The tapasin
      dependence of HLA class I alleles bearing different residues at position 114
      decreases in the order of acidity, with high tapasin dependence for acidic amino
      acids (aspartic acid and glutamic acid), moderate dependence for neutral amino
      acids (asparagine and glutamine), and low dependence for basic amino acids
      (histidine and arginine). A glutamic acid to histidine substitution at position
      114 allows the otherwise tapasin-dependent HLA-B4402 alleles to load high
      affinity peptides independently of tapasin and to have surface expression levels
      comparable to the levels seen in the presence of tapasin. The opposite
      substitution, histidine to glutamic acid at position 114, is sufficient to change
      the HLA-B2705 allele from the tapasin-independent to the tapasin-dependent
      phenotype. Furthermore, analysis of point mutants at position 114 reveals that
      tapasin plays a principal role in transforming the peptide-binding groove into a
      high-affinity, peptide-receptive conformation. The natural polymorphisms in HLA
      class I H chains that selectively affect tapasin-dependent peptide loading
      provide insights into the functional interaction of tapasin with MHC class I
      molecules.

PMID- 12517963
TI  - The GDP exchange factor AND-34 is expressed in B cells, associates with HEF1, and
      activates Cdc42.
AB  - AND-34, a novel GDP exchange factor, is expressed constitutively at significant
      levels in murine splenic B cells, but not in murine splenic T cells or
      thymocytes. In B cell lines, anti-IgM treatment up-regulates AND-34 transcript
      levels. B cell AND-34 associates with both the docking molecules p130Cas and
      HEF1. AND-34 binds by its GDP exchange factor domain to the C terminus of HEF1, a
      region of HEF1 previously implicated in apoptotic, adhesion, and cell cycle
      regulated signaling. Overexpression of AND-34 in murine B cell lines activates
      the Rho family GTPase Cdc42, but not Rac, Rho, RalA, or Rap1. Consistent with
      this, a subpopulation of AND-34 overexpressing B cells have long filamentous
      actin-containing cellular extensions. AND-34 overexpression augments both
      autophosphorylation and kinase activity of the Cdc42/Rac-responsive
      serine/threonine kinase PAK1. As previously reported for lymphoid cells
      transfected with constitutively active Cdc42, AND-34 overexpression inhibits SDF
      1alpha-induced B cell polarization. These studies suggest that p130Cas and HEF1
      associated AND-34 may regulate B cell adhesion and motility through a Cdc42
      mediated signaling pathway.

PMID- 12517964
TI  - A complex containing polypyrimidine tract-binding protein is involved in
      regulating the stability of CD40 ligand (CD154) mRNA.
AB  - CD40 ligand (CD154) expression has been shown to be regulated, in part, at the
      posttranscriptional level by a pathway of "regulated instability" of mRNA decay
      throughout a time course of T cell activation. This pathway is modulated at late
      times of activation by the binding of a stability complex (termed complex I) to a
      CU-rich region in the 3' untranslated region of the CD154 message. We have
      undertaken experiments to extend these findings and to analyze the cis-acting
      elements and trans-acting factors involved in this regulation. We have previously
      shown that the minimal binding sequence for complex I is a 63 nt CU-rich motif.
      However, our current study shows that when this site was deleted additional
      complex binding was observed upstream and downstream of the minimal binding
      region. Only after deletion of an extended region (termed Delta1515) was complex
      binding completely abolished. Analysis of complex binding using competition
      experiments revealed that the three adjacent regions bound related but not
      identical complexes. However, all three sites appeared to have a 55-kDa protein
      as the RNA-binding protein. Deletion of the Delta1515 region resulted in reduced
      transcript stability as measured by both in vitro and in vivo decay assays.
      Finally, using Abs against known RNA-binding proteins, we identified the
      polypyrimidine tract-binding protein (or heterogeneous nuclear ribonucleoprotein
      I) as a candidate RNA-binding component of complex I.

PMID- 12517965
TI  - Targeting with bovine CD154 enhances humoral immune responses induced by a DNA
      vaccine in sheep.
AB  - CD40-CD154 interactions play an important role in regulating humoral and cell
      mediated immune responses. Recently, these interactions have been exploited for
      the development of therapeutic and preventive treatments. The objective of this
      study was to test the ability of bovine CD154 to target a plasmid-encoded Ag to
      CD40-expressing APCs. To achieve this, a plasmid coding for bovine CD154 fused to
      a truncated secreted form of bovine herpesvirus 1 glycoprotein D (tgD), pSLIAtgD
      CD154, was constructed. The chimeric tgD-CD154 was expressed in vitro in COS-7
      cells and reacted with both glycoprotein D- and CD154-specific Abs. Both tgD and
      tgD-CD154 were capable of binding to epithelial cells, whereas only tgD-CD154
      bound to B cells. Furthermore, dual-labeling of ovine PBMCs revealed that tgD
      CD154 was bound by primarily B cells. The functional integrity of the tgD-CD154
      chimera was confirmed by the induction of both IL-4-dependent B cell
      proliferation and tgD-specific lymphoproliferative responses in vitro. Finally,
      sheep immunized with pSLIAtgD-CD154 developed a more rapid primary tgD-specific
      Ab response and a significantly stronger tgD-specific secondary response when
      compared with animals immunized with pSLIAtgD and control animals. Similarly,
      virus-neutralizing Ab titers were significantly higher after secondary
      immunization with pSLIAtgD-CD154. These results demonstrate that using CD154 to
      target plasmid-expressed Ag can significantly enhance immune responses induced by
      a DNA vaccine.

PMID- 12517966
TI  - Identification of IFN regulatory factor-1 binding site in IL-12 p40 gene
      promoter.
AB  - IL-12 is a heterodimer composed of p40 and p35 and is a key cytokine that
      functions to protect the host from viral and microbial infections. IL-12 links
      the innate immune system with the acquired immune system during infection, and
      induces differentiation of type 1 T cells that play an important role in the
      eradication of microbes. The induction of the IL-12 p40 gene is regulated by NF
      kappaB in the presence of IFN-gamma. IFN-gamma induces IFN regulatory factor-1
      (IRF-1), which in turn induces the transcription of the IL-12 p40 gene. However,
      the IRF-1 binding site in the promoter region of the IL-12 p40 gene has not yet
      been formally determined. In the present study, we demonstrated that IRF-1
      directly binds to the IL-12 p40 gene promoter and identified its binding site.
      The IRF-1 binding site in the promoter region of the IL-12 p40 gene is shown to
      be in the -72 to -58 area of the 5'-upstream region. The -63 to -61 position is
      the critical site within this region for the binding of IRF-1 to the IL-12 p40
      gene promoter. While IFN-gamma must be present for IL-12 p40 gene induction, the
      p35 gene is strongly induced by LPS, even in the absence of IFN-gamma, and
      therefore the induction of the p35 gene is IRF-1 independent.

PMID- 12517967
TI  - IL-10 modulates host responses and lung damage induced by Pneumocystis carinii
      infection.
AB  - Host responses to Pneumocystis carinii infection mediate impairment of pulmonary
      function and contribute to the pathogenesis of pneumonia. IL-10 is known to
      inhibit inflammation and reduce the severity of pathology caused by a number of
      infectious organisms. In the present studies, IL-10-deficient (IL-10 knockout
      (KO)) mice were infected with P. carinii to determine whether the severity of
      pathogenesis and the efficiency of clearance of the organisms could be altered in
      the absence of IL-10. The clearance kinetics of P. carinii from IL-10 KO mice was
      significantly enhanced compared with that of wild-type (WT) mice. This
      corresponded to a more intense CD4(+) and CD8(+) T cell response as well as an
      earlier neutrophil response in the lungs of IL-10 KO mice. Furthermore, IL-12, IL
      18, and IFN-gamma were found in the bronchoalveolar lavage fluids at earlier time
      points in IL-10 KO mice suggesting that alveolar macrophages were activated
      earlier than in WT mice. However, when CD4(+) cells were depleted from P. carinii
      infected IL-10 KO mice, the ability to enhance clearance was lost. Furthermore,
      CD4-depleted IL-10 KO mice had significantly more lung injury than CD4-depleted
      WT mice even though the intensity of the inflammatory responses was similar. This
      was characterized by increased vascular leakage, decreased oxygenation, and
      decreased arterial pH. These data indicate that IL-10 down-regulates the immune
      response to P. carinii in WT mice; however, in the absence of CD4(+) T cells, IL
      10 plays a critical role in controlling lung damage independent of modulating the
      inflammatory response.

PMID- 12517968
TI  - Autocrine type I IFN and contact with endothelium promote the presentation of
      influenza A virus by monocyte-derived APC.
AB  - Purified monocytes infected with influenza A virus do not become mature dendritic
      cells (DCs) and they present viral peptides poorly to autologous memory T cells.
      In this study, we investigated whether influenza A-infected monocytes matured to
      DCs with a high capacity to stimulate T cells when they were infected with
      influenza A virus in a model tissue setting wherein they were cocultured with
      endothelium grown on a type I collagen matrix. Intercellular interactions with
      endothelium strongly promoted the Ag-presenting capacity of monocyte-derived
      cells infected with influenza A virus, and the heterologous coculture system also
      enhanced production of IFN-alpha by monocytes in the absence of plasmacytoid
      cells. Production of IFN-alpha in the presence of endothelium correlated with
      monocyte differentiation to mature DCs and their ability to stimulate
      proliferation and IFN-gamma production by autologous T cells. Monocyte-derived
      cells that developed into migratory DCs promoted proliferation of influenza A
      virus-specific CD4(+) and CD8(+) cells, whereas those that developed into
      macrophages promoted proliferation of CD8(+) T cells only. This onset of APC
      activity could be partially blocked with Ab to the IFN-alphabeta receptor when
      monocytes were infected with UV-treated virus, but neutralizing this pathway was
      inconsequential when monocytes were infected with live virus. Thus, type I IFN
      and direct contact with endothelium promote development of influenza A virus
      presenting activity in monocyte-derived cells in a setting in which this
      differentiation does not depend on plasmacytoid cells. However, when infected
      with live influenza virus, the role of type I IFN in mediating differentiation
      and Ag-presenting capacity is expendable, apparently due to other mechanisms of
      virus-mediated activation.

PMID- 12517969
TI  - Novel quantitative trait loci controlling development of experimental autoimmune
      encephalomyelitis and proportion of lymphocyte subpopulations.
AB  - The B10.RIII mouse strain (H-2(r)) develops chronic experimental autoimmune
      encephalomyelitis (EAE) upon immunization with the myelin basic protein 89-101
      peptide. EAE was induced and studied in a backcross between B10.RIII and the EAE
      resistant RIIIS/J strain (H-2(r)), and a complete genome scan with microsatellite
      markers was performed. Five loci were significantly linked to different traits
      and clinical subtypes of EAE on chromosomes 1, 5, 11, 15, and 16, three of the
      loci having sex specificity. The quantitative trait locus on chromosome 15 partly
      overlapped with the Eae2 locus, previously identified in crosses between the
      B10.RIII and RIIIS/J mouse strains. The loci on chromosomes 11 and 16 overlapped
      with Eae loci identified in other mouse crosses. By analyzing the backcross
      animals for lymphocyte phenotypes, the proportion of B and T cells in addition to
      the levels of CD4(+)CD8(-) and CD4(-)CD8(+) T cells and the CD4(+)/CD8(+) ratio
      in spleen were linked to different loci on chromosomes 1, 2, 3, 5, 6, 11, and 15.
      On chromosome 16, we found significant linkage to spleen cell proliferation.
      Several linkages overlapped with the quantitative trait loci for disease
      phenotypes. The identification of subphenotypes that are linked to the same loci
      as disease traits could be most useful in the search for candidate genes and
      biological pathways involved in the pathological process.

PMID- 12517970
TI  - Acceleration of human neutrophil apoptosis by TRAIL.
AB  - Neutrophil granulocytes have a short lifespan, with their survival limited by a
      constitutive program of apoptosis. Acceleration of neutrophil apoptosis following
      ligation of the Fas death receptor is well-documented and TNF-alpha also has a
      transient proapoptotic effect. We have studied the role of the death receptor
      ligand TRAIL in human neutrophils. We identified the presence of mRNAs for TRAIL,
      TRAIL-R2, and TRAIL-R3, and cell surface expression of TRAIL-R2 and -R3 in
      neutrophil populations. Neutrophil apoptosis is specifically accelerated by
      exposure to a leucine zipper-tagged form of TRAIL, which mimics cell surface
      TRAIL. Using blocking Abs to TRAIL receptors, specifically TRAIL-R2, and a TRAIL
      R1:FcR fusion protein, we have excluded a role for TRAIL in regulating
      constitutive neutrophil apoptosis. No additional proapoptotic effect of leucine
      zipper TRAIL was identified following TRAIL treatment of neutrophils in the
      presence of gliotoxin, an inhibitor of NF-kappaB, suggesting TRAIL does not
      activate NF-kappaB in human neutrophils. TRAIL treatment of human neutrophils did
      not induce a chemotactic response. The susceptibility of neutrophils to TRAIL
      mediated apoptosis suggests a role for TRAIL in the regulation of inflammation
      and may provide a mechanism for clearance of neutrophils from sites of
      inflammation.

PMID- 12517971
TI  - Role of vesicle-associated membrane protein-2, through Q-soluble N-ethylmaleimide
      sensitive factor attachment protein receptor/R-soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor interaction, in the exocytosis of specific and
      tertiary granules of human neutrophils.
AB  - We have examined the role of the R-soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) synaptobrevin-2/vesicle-associated membrane
      protein (VAMP)-2 in neutrophil exocytosis. VAMP-2, localized in the membranes of
      specific and gelatinase-containing tertiary granules in resting human
      neutrophils, resulted translocated to the cell surface following neutrophil
      activation under experimental conditions that induced exocytosis of specific and
      tertiary granules. VAMP-2 was also found on the external membrane region of
      granules docking to the plasma membrane in activated neutrophils. Specific Abs
      against VAMP-2 inhibited Ca(2+) and GTP-gamma-S-induced exocytosis of CD66b
      enriched specific and tertiary granules, but did not affect exocytosis of CD63
      enriched azurophilic granules, in electropermeabilized neutrophils. Tetanus toxin
      disrupted VAMP-2 and inhibited exocytosis of tertiary and specific granules.
      Activation of neutrophils led to the interaction of VAMP-2 with the plasma
      membrane Q-SNARE syntaxin 4, and anti-syntaxin 4 Abs inhibited exocytosis of
      specific and tertiary granules in electropermeabilized neutrophils.
      Immunoelectron microscopy showed syntaxin 4 on the plasma membrane contacting
      with docked granules in activated neutrophils. These data indicate that VAMP-2
      mediates exocytosis of specific and tertiary granules, and that Q-SNARE/R-SNARE
      complexes containing VAMP-2 and syntaxin 4 are involved in neutrophil exocytosis.

PMID- 12517972
TI  - Cyclooxygenase-2 expression by nonsteroidal anti-inflammatory drugs in human
      airway smooth muscle cells: role of peroxisome proliferator-activated receptors.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to modulate
      cyclooxygenase (COX)-2 expression, but the mechanisms involved are controversial
      and may be cell specific. We show in this study that indomethacin (Indo),
      flurbiprofen (Flur), and the selective COX-2 inhibitor NS-398 induced COX-2
      expression and markedly enhanced IL-1beta-induced COX-2 expression in human
      airway smooth muscle (HASM) cells. These effects were not reversed by exogenous
      PGE(2), suggesting that they are prostanoid-independent. Indeed, PGE(2) also
      induced and enhanced IL-1beta-induced COX-2 expression. Peroxisome proliferator
      activated receptor (PPAR) alpha and PPARgamma (not PPARbeta) were expressed in
      HASM cells. PPARgamma activators ciglitizone (Cig) and 15-Deoxy-Delta(12,14)
      PGJ(2) (15d-PGJ(2)), but not the PPARalpha activator WY-14643, mimicked the
      effect of NSAIDs on COX-2 expression. Treatment with Flur, NS-398, Cig, and 15d
      PGJ(2) alone, but not Indo and WY-14643, elevated COX activity; however, neither
      enhanced IL-1beta-induced COX activity. Pretreatment with dexamethasone
      suppressed COX-2 expression, PGE(2) release, and COX activity induced by NS-398,
      Cig, IL-1beta, alone or in combination. Unlike IL-1beta, NS-398 and Cig did not
      cause NF-kappaB (p65) nuclear translocation, nor did they further enhance IL
      1beta-induced NF-kappaB translocation, but they stimulated PPARgamma
      translocation. Indo, NS-398, Flur, and 15d-PGJ(2), but not WY-14643, induced
      transcriptional activity of a COX-2 reporter construct containing the peroxisome
      proliferator response element (PPRE) on their own and enhanced the effect of IL
      1beta, but had no effect on a COX-2 reporter construct lacking the PPRE. The
      results suggest that COX-2 expression by NSAIDs is biologically functional,
      prostanoid-independent, and involves PPARgamma activation, and provide the first
      direct evidence that the PPRE in the promoter is required for NSAID-induced COX-2
      expression.

PMID- 12517973
TI  - CpG DNA induces self and cross-hyporesponsiveness of RAW264.7 cells in response
      to CpG DNA and lipopolysaccharide: alterations in IL-1 receptor-associated kinase
      expression.
AB  - Exposure of macrophages to LPS induces a state of hyporesponsiveness to
      subsequent challenge with LPS. It has not been known whether previous exposure to
      CpG DNA induces a similar suppressive response to subsequent stimulation with CpG
      DNA. In the present study, we demonstrate that pretreatment with CpG DNA induces
      suppression of cytokine release in a murine macrophage-like cell RAW264.7 in
      response to subsequent challenge by CpG DNA. Additionally, CpG DNA-mediated
      activation of mitogen-activated protein kinases, including c-Jun NH(2)-terminal
      kinase, extracellular signal-regulated kinase, and p38, and activation of
      transcription factors AP-1, CREB, NF-kappaB, and STAT1 are greatly suppressed in
      the cells pre-exposed to CpG DNA. Pretreatment with CpG DNA also partially
      inhibited LPS-mediated production of cytokines and activation of mitogen
      activated protein kinases and transcription factors. Neither LPS nor CpG DNA
      treatment inhibited Toll-like receptor 4, MD2, Toll-like receptor 9, myeloid
      differentiation factor 88, Toll/IL-1R domain-containing adaptor protein, Tollip,
      and TNF-alpha receptor-associated factor 6 expression. Interestingly, CpG DNA or
      LPS stimulation led to the inhibition of IL-1R-associated kinase expression.
      These results indicate that CpG DNA-induced refractory of RAW264.7 cells may be,
      at least in part, due to suppressed IL-1R-associated kinase expression.

PMID- 12517974
TI  - New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental
      autoimmune encephalomyelitis.
AB  - Myelin oligodendrocyte glycoprotein-induced experimental autoimmune
      encephalomyelitis (EAE) is an inflammatory disease in rats that closely mimics
      many clinical and histopathological aspects of multiple sclerosis. Non-MHC
      quantitative trait loci regulating myelin oligodendrocyte glycoprotein-induced
      EAE have previously been identified in the EAE-permissive strain, DA, on rat
      chromosomes 4, 10, 15, and 18. To find any additional gene loci in another well
      known EAE-permissive strain and thereby to assess any genetic heterogeneity in
      the regulation of the disease, we have performed a genome-wide linkage analysis
      in a reciprocal (LEW.1AV1 x PVG.1AV1) male/female F(2) population (n = 185). We
      examined reciprocal crosses, but no parent-of-origin effect was detected. The
      parental rat strains share the RT1(av1) MHC haplotype; thus, non-MHC genes
      control differences in EAE susceptibility. We identified Eae16 on chromosome 8
      and Eae17 on chromosome 13, significantly linked to EAE phenotypes. Two loci, on
      chromosomes 1 and 17, respectively showed suggestive linkage to clinical and
      histopathological EAE phenotypes. Eae16 and Eae17 differ from those found in
      previously studied strain combinations, thus demonstrating genetic heterogeneity
      of EAE. Furthermore, we detected a locus-specific parent-of-origin effect with
      suggestive linkage in Eae17. Further genetic and functional dissection of these
      loci may disclose critical disease-regulating molecular mechanisms.

PMID- 12517975
TI  - Regulation of cyclooxygenase-2 expression by macrophages in response to double
      stranded RNA and viral infection.
AB  - In this study the regulation of macrophage expression of cyclooxygenase-2 (COX-2)
      in response to dsRNA and virus infection was examined. Treatment of RAW 264.7
      macrophages with dsRNA results in COX-2 mRNA accumulation and protein expression
      and the production of PGE(2). Similar to dsRNA, encephalomyocarditis virus (EMCV)
      infection of RAW 264.7 cells stimulates COX-2 expression and PGE(2) accumulation.
      The dsRNA-dependent protein kinase (PKR), which has been shown to participate in
      the regulation of gene expression in response to dsRNA and virus infection, does
      not appear to participate in the regulation of COX-2 expression by macrophages.
      Expression of dominant negative mutants of PKR in RAW 264.7 cells fails to
      attenuate dsRNA- and EMCV-induced COX-2 expression or PGE(2) production.
      Furthermore, dsRNA and EMCV stimulate COX-2 expression and PGE(2) accumulation to
      similar levels in macrophages isolated from wild-type and PKR-deficient mice.
      Recently, a novel PKR-independent role for the calcium-independent phospholipase
      A(2) (iPLA(2)) in the regulation of inducible NO synthase expression by
      macrophages in response to virus infection has been identified. The selective
      iPLA(2) suicide substrate inhibitor bromoenol lactone prevents dsRNA- and EMCV
      stimulated inducible NO synthase expression; however, bromoenol lactone does not
      attenuate dsRNA- or EMCV-induced COX-2 expression by macrophages. In contrast,
      inhibition of NF-kappaB activation prevents dsRNA-stimulated COX-2 expression and
      PGE(2) accumulation by macrophages. These findings indicate that virus infection
      and treatment with dsRNA stimulate COX-2 expression by a mechanism that requires
      the activation of NF-kappaB and that is independent of PKR or iPLA(2) activation.

PMID- 12517976
TI  - Enhanced Th2 cell-mediated allergic inflammation in Tyk2-deficient mice.
AB  - Allergic inflammation is mediated by Th2 cell-derived cytokines, including IL-4,
      IL-5, and IL-13, and down-regulated by IFN-gamma and IL-12. Tyk2 is a member of
      the Janus family of protein tyrosine kinases and is activated by a variety of
      cytokines: IFN-alphabeta, IL-6, IL-10, IL-12, and IL-13. In this study, we
      investigated the role of Tyk2 in the regulation of Ag-induced Th cell
      differentiation and Ag-induced allergic inflammation in the airways using Tyk2
      deficient (Tyk2(-/-)) mice. When splenocytes were stimulated with antigenic
      peptide, IL-12-mediated Th1 cell differentiation was decreased, but IL-4-mediated
      Th2 cell differentiation was increased in Tyk2(-/-) mice. In vivo, Ag-specific
      IgE and IgG1 production was increased, but Ag-specific IgG2a production was
      decreased in Tyk2(-/-) mice as compared with those in control mice. In addition,
      Ag-induced eosinophil and CD4(+) T cell recruitment, as well as the production of
      Th2 cytokines in the airways, was increased in Tyk2(-/-) mice. Adoptive transfer
      experiments revealed that CD4(+) T cells were responsible for the enhanced Ag
      induced eosinophil recruitment in Tyk2(-/-) mice. In contrast, although the level
      of IL-13 was increased in the airways of Tyk2(-/-) mice after Ag inhalation, the
      number of goblet cells, as well as Muc5ac mRNA expression, was decreased in Tyk2(
      /-) mice. Together, these results indicate that Tyk2 plays a bilateral role in
      the regulation of allergic inflammation in the airways: Tyk2 plays a role in the
      down-regulation of Th2 cell-mediated Ab production and eosinophil recruitment in
      the airways by regulating Th1/Th2 balance toward Th1-type, while Tyk2 is
      necessary for the induction of IL-13-mediated goblet cell hyperplasia in the
      airways.

PMID- 12517977
TI  - Chemoattraction of human T cells by IL-18.
AB  - Cell locomotion is crucial to the induction of an effective immune response. We
      report here the chemoattraction of CD4(+) T cells by IL-18, a member of the IL-1
      cytokine family. Recombinant IL-18 increased the proportion of T cells in
      polarized morphology in vitro and stimulated their subsequent invasion into
      collagen gels in an IL-18 concentration gradient-dependent manner.
      Immunofluorescent microscopy studies determined that the major cell type
      responding to IL-18 was IL-18R(+)CD4(+). Importantly, synovial CD4(+) T cells
      from patients with rheumatoid arthritis responded to IL-18, adopting polarized
      morphology and gel invasion without further activation ex vivo, indicating the
      physiologic relevance of our observations. Finally, injection of rIL-18 into the
      footpad of DBA/1 mice led to local accumulation of inflammatory cells. These data
      therefore demonstrate for the first time lymphocyte chemoattractant properties of
      a member of the IL-1 cytokine family and its relevance in inflammatory diseases.

PMID- 12517978
TI  - Selective I kappa B kinase expression in airway epithelium generates neutrophilic
      lung inflammation.
AB  - To determine whether NF-kappaB activation is sufficient to generate lung
      inflammation in vivo, we selectively expressed a constitutively active form of
      IkappaB kinase 1 (cIKK1) or IkappaB kinase 2 (cIKK2) in airway epithelium. After
      intratracheal administration of adenoviral vectors expressing cIKK1 or cIKK2 to
      transgenic reporter mice that express Photinus luciferase under the control of an
      NF-kappaB-dependent promoter, we detected significantly increased luciferase
      activity over time (up to 96 h). Compared with control mice treated with
      adenoviral vectors expressing beta-galactosidase, lung bioluminescence and tissue
      luciferase activity were increased in NF-kappaB reporter mice treated with
      adenovirus (Ad)-cIKK1 or Ad-cIKK2. NF-kappaB activation in lungs of Ad-cIKK1- and
      Ad-cIKK2-treated mice was confirmed by immunoblots for RelA and EMSA from lung
      nuclear protein extracts. Mice treated with Ad-cIKK1 or Ad-cIKK2 showed induction
      of mRNA expression of several chemokines and cytokines in lung tissue. In lung
      lavage fluid, mice treated with Ad-cIKK1 or Ad-cIKK2 showed elevated
      concentrations of NF-kappaB-dependent chemokines macrophage-inflammatory protein
      2 and KC and increased numbers of neutrophils. Coadministration of adenoviral
      vectors expressing a transdominant inhibitor of NF-kappaB with Ad-cIKK1 or Ad
      cIKK2 resulted in abrogated NF-kappaB activation and other parameters of lung
      inflammation, demonstrating that the observed inflammatory effects of Ad-cIKK1
      and Ad-cIKK2 were dependent on NF-kappaB activation by these kinases. These data
      show that selective expression of IkappaB kinases in airway epithelium results in
      NF-kappaB activation, inflammatory mediator production, and neutrophilic lung
      inflammation. Therapies targeted to NF-kappaB in lung epithelium may be
      beneficial in treating inflammatory lung diseases.

PMID- 12517979
TI  - CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or
      colitis in HLA-B27 transgenic rats.
AB  - The class I MHC allele HLA-B27 is highly associated with the human
      spondyloarthropathies, but the basis for this association remains poorly
      understood. Transgenic rats with high expression of HLA-B27 develop a multisystem
      inflammatory disease that includes arthritis and colitis. To investigate whether
      CD8alphabeta T cells are needed in this disease, we depleted these cells in B27
      transgenic rats before the onset of disease by adult thymectomy plus short-term
      anti-CD8alpha mAb treatment. This treatment induced profound, sustained depletion
      of CD8alphabeta T cells, but failed to suppress either colitis or arthritis. To
      address the role of CD8alpha(+)beta(-) cells, we studied four additional groups
      of B27 transgenic rats treated with: 1) continuous anti-CD8alpha mAb, 2)
      continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8alpha
      regimen, or 4) no treatment. Arthritis occurred in approximately 40% of each
      group, but was most significantly reduced in severity in the anti-CD8alpha
      treated group. In addition to CD8alphabeta T cells, two sizeable CD8alpha(+)beta(
      ) non-T cell populations were also reduced by the anti-CD8alpha treatment: 1) NK
      cells, and 2) a CD4(+)CD8(+)CD11b/c(+)CD161a(+)CD172a(+) monocyte population that
      became expanded in diseased B27 transgenic rats. These data indicate that HLA-B27
      retricted CD8(+) T cells are unlikely to serve as effector cells in the
      transgenic rat model of HLA-B27-associated disease, in opposition to a commonly
      invoked hypothesis concerning the role of B27 in the spondyloarthropathies. The
      data also suggest that one or more populations of CD8alpha(+)beta(-) non-T cells
      may play a role in the arthritis that occurs in these rats.

PMID- 12517980
TI  - Diverse repertoire of HIV-1 p24-specific, IFN-gamma-producing CD4+ T cell clones
      following immune reconstitution on highly active antiretroviral therapy.
AB  - HIV-1 Ag-specific CD4(+) T cell proliferative responses in human subjects with
      advanced, untreated HIV-1 disease are often weak or undetectable. Conversely, HIV
      1-specific CD4(+) T cell proliferation is occasionally detected following
      suppression of HIV-1 replication with highly active antiretroviral therapy
      (HAART). These observations suggest that unchecked HIV-1 replication may lead to
      depletion or dysfunction of HIV-1-specific CD4(+) T cells, and that these defects
      may be partially corrected by viral suppression and subsequent immune
      reconstitution. However, the impact of this immune reconstitution on the
      repertoire of HIV-1-specific CD4(+) T cells has not been thoroughly evaluated. To
      examine the HIV-1-specific CD4(+) T cell repertoire in this clinical setting, we
      established HIV-1 p24-specific CD4(+) T cell clones from a successfully HAART
      treated subject whose pretreatment peripheral CD4 count was 0 cells/ micro l.
      Eleven different p24-specific CD4(+) T cell clonotypes were distinguished among
      13 clones obtained. Most clones produced both IFN-gamma and IL-4 upon Ag
      stimulation. Clones targeted eight distinct epitopes that varied in their
      conservancy among HIV-1 strains, and responses were restricted by one of three
      MHC II molecules. Clones showed a range of functional avidities for both protein
      and peptide Ags. Additional studies confirmed that multiple HIV-1 p24-derived
      epitopes were targeted by IFN-gamma-producing CD4(+) cells from subjects first
      treated with HAART during advanced HIV-1 disease (median, 4.5 peptides/subject;
      range, 3-6). These results suggest that in HAART-treated subjects whose
      peripheral CD4(+) T cell pools were once severely depleted, the HIV-1-specific
      CD4(+) T cell repertoire may include a diverse array of clonotypes targeting
      multiple HIV-1 epitopes.

PMID- 12517981
TI  - Biological impacts of deep-sea carbon dioxide injection inferred from indices of
      physiological performance.
AB  - A recent proposal to store anthropogenic carbon dioxide in the deep ocean is
      assessed here with regard to the impacts on deep-living fauna. The stability of
      the deep-sea has allowed the evolution of species ill-equipped to withstand rapid
      environmental changes. Low metabolic rates of most deep-sea species are
      correlated with low capacities for pH buffering and low concentrations of ion
      transport proteins. Changes in seawater carbon dioxide partial pressure
      (P(CO(2))) may thus lead to large cellular P(CO(2)) and pH changes. Oxygen
      transport proteins of deep-sea animals are also highly sensitive to changes in
      pH. Acidosis leads to metabolic suppression, reduced protein synthesis,
      respiratory stress, reduced metabolic scope and, ultimately, death. Deep-sea
      CO(2) injection as a means of controlling atmospheric CO(2) levels should be
      assessed with careful consideration of potential biological impacts. In order to
      properly evaluate the risks within a relevant timeframe, a much more aggressive
      approach to research is warranted.

PMID- 12517982
TI  - Redox signaling in the growth and development of colonial hydroids.
AB  - Redox signaling provides a quick and efficient mechanism for clonal or colonial
      organisms to adapt their growth and development to aspects of the environment,
      e.g. the food supply. A 'signature' of mitochondrial redox signaling,
      particularly as mediated by reactive oxygen species (ROS), can be elucidated by
      experimental manipulation of the electron transport chain. The major sites of ROS
      formation are found at NADH dehydrogenase of complex I and at the interface
      between coenzyme Q and complex III. Inhibitors of complex III should thus
      upregulate ROS from both sites; inhibitors of complex I should upregulate ROS
      from the first but not the second site, while uncouplers of oxidative
      phosphorylation should downregulate ROS from both sites. To investigate the
      possibility of such redox signaling, perturbations of colony growth and
      development were carried out using the hydroid Podocoryna carnea. Oxygen uptake
      of colonies was measured to determine comparable physiological doses of antimycin
      A(1) (an inhibitor of complex III), rotenone (an inhibitor of complex I) and
      carbonyl cyanide m-chlorophenylhydrazone (CCCP; an uncoupler of oxidative
      phosphorylation). Using these doses, clear effects on colony growth and
      development were obtained. Treatment with antimycin A(1) results in 'runner-like'
      colony growth, with widely spaced polyps and stolon branches, while treatment
      with CCCP results in 'sheet-like' growth, with closely spaced polyps and stolon
      branches. Parallel results have been obtained previously with azide, an inhibitor
      of complex IV, and dinitrophenol, another uncoupler of oxidative phosphorylation.
      Perhaps surprisingly, rotenone produced effects on colony development similar to
      those of CCCP. Assays of peroxides using 2',7'-dichlorofluorescin diacetate and
      fluorescent microscopy suggest a moderate difference in ROS formation between the
      antimycin and rotenone treatments. The second site of ROS formation (the
      interface between coenzyme Q and complex III) may thus predominate in the
      signaling that regulates colony development. The fat-rich, brine shrimp diet of
      these hydroids may be relevant in this context. Acyl CoA dehydrogenase, which
      catalyzes the first step in the mitochondrial beta-oxidation of fatty acids,
      carries electrons to coenzyme Q, thus bypassing complex I. These results support
      a role for redox signaling, mediated by ROS, in colony development. Nevertheless,
      other redox sensors between complexes I and III may yet be found.

PMID- 12517983
TI  - Modulation of ingested water absorption by Palestine sunbirds: evidence for
      adaptive regulation.
AB  - Nectarivorous birds feed on dilute sugar solutions containing trace amounts of
      amino acids and electrolytes. To meet their high mass-specific energy demands
      they must often deal with exceptionally high proportionate water fluxes. Despite
      nectar intake rates that may reach more than five times body mass per day,
      hummingbirds appear to absorb all ingested water. Here, we report the results of
      experiments designed to examine the relationship between nectar intake and water
      turnover in nectar-feeding Palestine sunbirds (Nectarinia osea). Like
      hummingbirds, sunbirds ingested large amounts of water. At the lowest sucrose
      concentration (292 mmol l(-1)), food intake rates reached 2.2 times body mass.
      Fractional and total water turnover increased linearly with water ingestion, but
      the fraction of ingested water absorbed by sunbirds decreased from 100% to 36%
      with increasing water intake rate. Palestine sunbirds may therefore avoid
      absorbing, and thus having to eliminate, up to 64% of their ingested water load
      when feeding on dilute nectars. To our knowledge, this is the first documentation
      of regulation of water flux across the gastrointestinal tract to the body. Our
      data suggest that sunbirds regulate transepithelial water flux independently of
      sugar absorption. These intriguing results open the door to many questions about
      how water transport is regulated in the vertebrate gastrointestinal tract. We
      suggest that intestinal water and body water form two separate but interacting
      pools in nectar-feeding birds. Convergence in diet has led to the evolution of
      many similar traits in hummingbirds and sunbirds. The physiological traits of
      these two groups that allow the processing of a water and sugar diet, however,
      may be very different.

PMID- 12517984
TI  - Maneuverability by the sea lion Zalophus californianus: turning performance of an
      unstable body design.
AB  - Maneuverability is critical to the performance of fast-swimming marine mammals
      that use rapid turns to catch prey. Overhead video recordings were analyzed for
      two sea lions (Zalophus californianus) turning in the horizontal plane. Unpowered
      turns were executed by body flexion in conjunction with use of the pectoral and
      pelvic flippers, which were used as control surfaces. A 90 degree bank angle was
      used in the turns to vertically orient the control surfaces. Turning radius was
      dependent on body mass and swimming velocity. Relative minimum radii were 9-17%
      of body length and were equivalent for pinnipeds and cetaceans. However, Zalophus
      had smaller turning radii at higher speeds than cetaceans. Rate of turn was
      inversely related to turn radius. The highest turn rate observed in Zalophus was
      690 degrees s(-1). Centripetal acceleration measured up to 5.1 g for Zalophus.
      Comparison with other marine mammals indicates that Zalophus has a morphology
      that enhances instability, thus providing enhanced turning performance. Enhanced
      turning performance is necessary for sea lions to forage after highly elusive
      prey in structurally complex environments.

PMID- 12517985
TI  - Hypometabolism, antioxidant defenses and free radical metabolism in the pulmonate
      land snail Helix aspersa.
AB  - The aim of this work was to evaluate the effect of a cycle of estivation and
      awakening on free radical metabolism in selected organs of the land snail Helix
      aspersa. Estivation for 20 days induced a 4.9- and 1.8-fold increase in selenium
      dependent glutathione peroxidase activity (Se-GPX) and in total glutathione
      levels (GSH-eq), respectively, in hepatopancreas when compared to activity in
      active animals 24 h after awakening. Foot muscle Se-GPX activity was also
      increased 3.9-fold during estivation, whereas GSH-eq did not vary. The activities
      of other antioxidant enzymes (catalase, superoxide dismutase, glutathione
      reductase and glutathione S-transferase) and glucose 6-phosphate dehydrogenase
      were unchanged in both organs. After 15 min of awakening, the glutathione
      disulphide (GSSG)/GSH-eq ratio increased significantly by 55% in hepatopancreas,
      slowly returning to the levels observed during estivation. The higher GSSG/GSH-eq
      ratio may be caused by increased formation of reactive oxygen species (ROS)
      during awakening. The levels of thiobarbituric acid reactive substances (TBARS)
      decreased from 49 to 30.7 nmol g(-1) wet mass in hepatopancreas after 5 min
      arousal and, after 30 min, TBARS rose significantly to 39.6 nmol g(-1) wet mass,
      gradually declining thereafter. The levels of lipid hydroperoxides in
      hepatopancreas and of carbonyl protein in foot muscle both decreased during
      awakening. The higher levels of products of free radical damage during estivation
      may have resulted from low levels of ROS formation associated with decreased
      rates of lipid hydroperoxide detoxification and oxidized protein turnover caused
      by metabolic depression. The regulation of the antioxidant system during
      hypometabolism may constitute a mechanism to minimize oxidative stress during
      cycles of estivation and awakening.

PMID- 12517986
TI  - Central effects of various ligands on drinking behavior in eels acclimated to
      seawater.
AB  - Intracranial injection of eel angiotensin II (eANG II, 5x10(-13)-5x10(-8) mol),
      acetylcholine (ACh, 5x10(-12)-5x10(-9) mol), substance P (5x10(-10) mol) and
      isoproterenol (a beta-adrenoceptor agonist, 5x10(-11)-5x10(-9) mol) enhanced
      water intake in the seawater eel. The effects of eANG II, ACh and isoproterenol
      were dose-dependent. By contrast, water intake was inhibited by intracranial
      injection of eel atrial natriuretic peptide (eANP, 5x10(-13)-5x10(-10) mol),
      serotonin (5-HT, 5x10(-12)-5x10(-8) mol), ghrelin (5x10(-12)-5x10(-10) mol),
      gamma-amino butyric acid (GABA, 5x10(-11)-5x10(-8) mol), prolactin (PRL, 5x10(
      10)-5x10(-9) mol), arginine vasotocin (AVT, 5x10(-12) mol), vasoactive intestinal
      peptide (VIP, 5x10(-11) mol), noradrenaline (5x10(-9) mol l(-1)) and
      phenylephrine (alpha-adrenoceptor agonist, 5x10(-11)-5x10(-9) mol). The
      inhibitory effects of eANP, 5-HT, ghrelin, GABA, PRL and phenylephrine were dose
      dependent. The intracranial stimulatory effect of eANG II was relatively long
      lasting compared with the intravenous effect. The stimulatory effect of
      intravenous eANG II disappeared immediately, and was followed by an inhibition,
      which could be well explained by an increase in eANP secretion from the atrium.

PMID- 12517987
TI  - The snakehead Channa asiatica accumulates alanine during aerial exposure, but is
      incapable of sustaining locomotory activities on land through partial amino acid
      catabolism.
AB  - The freshwater snakehead Channa asiatica is an obligatory air-breather that
      resides in slow-flowing streams and in crevices near riverbanks in Southern
      China. In its natural habitat, it may encounter bouts of aerial exposure during
      the dry seasons. In the laboratory, the ammonia excretion rate of C. asiatica
      exposed to terrestrial conditions in a 12 h:12 h dark:light regime was one
      quarter that of the submerged control. Consequently, the ammonia contents in the
      muscle, liver and plasma increased significantly, and C. asiatica was able to
      tolerate quite high levels of ammonia in its tissues. Urea was not the major
      product of ammonia detoxification in C. asiatica, which apparently did not
      possess a functioning ornithine urea cycle. Rather, alanine increased fourfold to
      12.6 micromol g(-1) in the muscle after 48 h of aerial exposure. This is the
      highest level known in adult teleosts exposed to air or an ammonia-loading
      situation. The accumulated alanine could account for 70% of the deficit in
      ammonia excretion during this period, indicating that partial amino acid
      catabolism had occurred. This would allow the utilization of certain amino acids
      as energy sources and, at the same time, maintain the new steady state levels of
      ammonia in various tissues, preventing them from rising further. There was a
      reduction in the aminating activity of glutamate dehydrogenase from the muscle
      and liver of specimens exposed to terrestrial conditions. Such a phenomenon has
      not been reported before and could, presumably, facilitate the entry of alpha
      ketoglutarate into the Krebs cycle instead of its amination to glutamate, as has
      been suggested elsewhere. However, in contrast to mudskippers, C. asiatica was
      apparently unable to reduce the rates of proteolysis and amino acid catabolism,
      because the reduction in nitrogenous excretion during 48 h of aerial exposure was
      completely balanced by nitrogenous accumulation in the body. Alanine accumulation
      also occurred in specimens exposed to terrestrial conditions in total darkness,
      with no change in the total free amino acid content in the muscle. Exercise on
      land led to a decrease in glycogen content, and an increase in lactate levels,
      with no significant effect on ammonia and alanine contents in the muscle of C.
      asiatica. Hence, unlike the mudskipper Periophthalmodon schlosseri, C. asiatica
      was incapable of increasing the rate of partial amino acid catabolism to sustain
      locomotory activities on land. Alanine formation therefore appears to be a common
      strategy adopted by obligatory air-breathing fishes to avoid ammonia toxicity
      (not a strategy to detoxify ammonia) on land, but not all of them can utilize it
      to fuel muscular activities.

PMID- 12517989
TI  - Novel natural ligands for Drosophila olfactory receptor neurones.
AB  - Due to its well-defined genome, the fruitfly Drosophila melanogaster has become a
      very important model organism in olfactory research. Despite all the research
      invested, few natural odour ligands have been identified. By using a combined gas
      chromatographic-single receptor neurone recording technique (GC-SC), we set out
      to identify active odour molecules in head space-collected volatiles from
      preferred food sources, i.e. different overripe or rotting fruit. In total, we
      performed 101 GC-SC experiments on 85 contacted sensilla. Using GC-mass
      spectrometry, we identified 24 active compounds. Synthetic samples of these
      compounds were used to establish dose-response curves for several of the receptor
      neurone types encountered. The response patterns of individual neurones were
      repeatable, and neurones were found to reside in stereotyped pairs. In total, we
      identified eight distinct sensillum types based on response profiles of 12
      olfactory receptor neurone types. In most recordings, a single GC peak would
      produce a strong response, whereas a few other, often chemically related,
      compounds would produce weaker responses. The GC-SC recordings revealed that the
      olfactory receptor neurones investigated were often selective and could be
      divided into distinct functional types with discrete characteristics. Dose
      response investigations revealed very low response thresholds to the tested
      compounds. Six of the novel ligands were also tested for their behavioural effect
      in a T-maze set up. Of these, five elicited attraction and one elicited
      repulsion.

PMID- 12517990
TI  - Hydrodynamic stability of swimming in ostraciid fishes: role of the carapace in
      the smooth trunkfish Lactophrys triqueter (Teleostei: Ostraciidae).
AB  - The hydrodynamic bases for the stability of locomotory motions in fishes are
      poorly understood, even for those fishes, such as the rigid-bodied smooth
      trunkfish Lactophrys triqueter, that exhibit unusually small amplitude recoil
      movements during rectilinear swimming. We have studied the role played by the
      bony carapace of the smooth trunkfish in generating trimming forces that self
      correct for instabilities. The flow patterns, forces and moments on and around
      anatomically exact, smooth trunkfish models positioned at both pitching and
      yawing angles of attack were investigated using three methods: digital particle
      image velocimetry (DPIV), pressure distribution measurements, and force balance
      measurements. Models positioned at various pitching angles of attack within a
      flow tunnel produced well-developed counter-rotating vortices along the ventro
      lateral keels. The vortices developed first at the anterior edges of the ventro
      lateral keels, grew posteriorly along the carapace, and reached maximum
      circulation at the posterior edge of the carapace. The vortical flow increased in
      strength as pitching angles of attack deviated from 0 degrees, and was located
      above the keels at positive angles of attack and below them at negative angles of
      attack. Variation of yawing angles of attack resulted in prominent dorsal and
      ventral vortices developing at far-field locations of the carapace; far-field
      vortices intensified posteriorly and as angles of attack deviated from 0 degrees.
      Pressure distribution results were consistent with the DPIV findings, with areas
      of low pressure correlating well with regions of attached, concentrated
      vorticity. Lift coefficients of boxfish models were similar to lift coefficients
      of delta wings, devices that also generate lift through vortex generation.
      Furthermore, nose-down and nose-up pitching moments about the center of mass were
      detected at positive and negative pitching angles of attack, respectively. The
      three complementary experimental approaches all indicate that the carapace of the
      smooth trunkfish effectively generates self-correcting forces for pitching and
      yawing motions--a characteristic that is advantageous for the highly variable
      velocity fields experienced by trunkfish in their complex aquatic environment.
      All important morphological features of the carapace contribute to producing the
      hydrodynamic stability of swimming trajectories in this species.

PMID- 12517988
TI  - Characterisation of intestinal peptide transporter of the Antarctic
      haemoglobinless teleost Chionodraco hamatus.
AB  - H(+)/peptide cotransport was studied in brush-border membrane vesicles (BBMV)
      from the intestine of the haemoglobinless Antarctic teleost Chionodraco hamatus
      by monitoring peptide-dependent intravesicular acidification with the pH
      sensitive dye Acridine Orange. Diethylpyrocarbonate-inhibited intravesicular
      acidification was specifically achieved in the presence of extravesicular glycyl
      L-proline (Gly-L-Pro) as well as of glycyl-L-alanine (Gly-L-Ala) and D
      phenylalanyl-L-alanine (D-Phe-L-Ala). H(+)/Gly-L-Pro cotransport displayed
      saturable kinetics, involving a single carrier system with an apparent substrate
      affinity (K(m,app)) of 0.806+/-0.161 mmol l(-1). Using degenerated primers from
      eel and human (PepT1) transporter sequence, a reverse transcription-polymerase
      chain reaction (RT-PCR) signal was detected in C. hamatus intestine. RT-PCR
      paralleled kinetic analysis, confirming the hypothesis of the existence of a
      PepT1-type transport system in the brush-border membranes of icefish intestine.
      Functional expression of H(+)/peptide cotransport was successfully performed in
      Xenopus laevis oocytes after injection of poly(A)(+) RNA (mRNA) isolated from
      icefish intestinal mucosa. Injection of mRNA stimulated D-Phe-L-Ala uptake in a
      dose-dependent manner and an excess of glycyl-L-glutamine inhibited this
      transport. H(+)/peptide cotransport in the Antarctic teleost BBMV exhibited a
      marked difference in temperature optimum with respect to the temperate teleost
      Anguilla anguilla, the maximal activity rate occurring at approximately 0 degrees
      C for the former and 25 degrees C for the latter. Temperature dependence of
      icefish and eel intestinal mRNA-stimulated uptake in the heterologous system
      (oocytes) was comparable.

PMID- 12517991
TI  - Measuring wing kinematics, flight trajectory and body attitude during forward
      flight and turning maneuvers in dragonflies.
AB  - A robust technique for determining the wing kinematics, body position and
      attitude of a free-flight dragonfly is described. The new method is based on a
      projected comb-fringe technique combined with the natural landmarks on a
      dragonfly, allowing us to establish the local body-centered coordinate system
      with high accuracy, and to measure the body attitude at any instant. The
      kinematic parameters, including wingbeat frequency, flapping angle, angle of
      attack, torsional angle and camber deformation, required no assumptions to be
      made with respect to wing geometry, deformability (except the assumption of rigid
      leading edges) or bilateral wing symmetry. Two typical flight behaviors, forward
      flight and turning maneuvers, of dragonflies Polycanthagyna melanictera Selys
      were measured and analyzed.

PMID- 12517992
TI  - Proprioceptors monitoring forces in a locust hind leg during kicking form
      negative feedback loops with flexor tibiae motor neurons.
AB  - In preparation for jumping and kicking, a locust slowly generates large forces in
      the femoral muscles of its hind legs and stores them in elastic distortions of
      the tendons and femoral cuticle. At the femoro-tibial joints, the semi-lunar
      processes are bent, the cuticle of the dorsal distal femur is crumpled, and the
      femur is expanded in a mediolateral direction. We have analysed whether these
      distortions are monitored by sense organs and whether the information they
      provide is used to limit the forces generated and thus prevent structural damage
      to the joint. The two sensory neurons comprising the lump receptor lie in a
      groove in the ventral part of the distal femur. The sensory neurons spike if
      force is applied to the flexor tendon when the joint is fully flexed, but not
      when it is extended. They also spike as the tendon of the flexor muscle slides
      into the ventral femoral groove when the tibia is fully flexed during the co
      contraction phase of kicking. Their spike frequency correlates with the extent of
      bending of a semi-lunar process that provides a quantifiable measure of the joint
      distortions. If the tibia is not fully flexed, however, then muscle contractions
      still cause distortions of the joint but these are not signalled by sensory
      spikes from the lump receptor. The lump receptor, therefore, does not respond
      primarily to the joint distortions but to the movements or force in the flexor
      tendon. Contractions of the flexor tibiae muscle caused by spikes in individual
      flexor motor neurons can evoke spikes in sensory neurons from the lump receptor
      when the joint is fully flexed. In turn, the sensory neurons cause a
      hyperpolarisation in particular flexor motor neurons in a polysynaptic negative
      feedback loop. The lump receptor could, therefore, regulate the output of the
      flexor motor neurons and, thus, limit the amount of force generated during co
      contraction. It may also contribute to the inhibition of the flexors at the end
      of co-contraction that allows rapid kicking movements to occur.

PMID- 12517993
TI  - Mechanics of cuticular elastic energy storage in leg joints lacking extensor
      muscles in arachnids.
AB  - Certain leg joints in arachnids lack extensor muscles and have elastically
      deformable transarticular sclerites spanning their arthrodial membranes, an
      arrangement consistent with a model in which flexor muscles load transarticular
      sclerites during flexion and energy from elastic recoil is used for extension.
      This study quantifies the potential contribution of elastic recoil to extension
      torque at joints of the fourth leg of representative arachnids. Extension torques
      of isolated joints with and without transarticular sclerites were measured as the
      joint was rotated through angles and at angular velocities comparable with those
      used by walking animals. The procedure was repeated with the joint subjected to
      different internal fluid pressures in order to assess the potential role of
      hydraulically induced extension. The efficiency of elastic energy storage
      (resilience) in the absence of internal fluid pressure was 70-90% for joints with
      well-developed transarticular sclerites, and the magnitude of torque was similar
      to those produced by different joint extension mechanisms in other arthropods.
      Increased internal fluid pressure acted synergistically with transarticular
      sclerites in some joints but had little or no effect in others. Joints that
      lacked both extensor muscles and transarticular sclerites appeared to be
      specialized for hydraulic extension, and joints operated by antagonistic muscles
      lacked apparent specializations for either elastic or hydraulic extension. It is
      well known that elastic energy storage is a significant contributor to propulsion
      in running vertebrates and certain arthropods, where elastic elements are loaded
      as the center of mass falls during one phase of the locomotor cycle. However,
      transarticular sclerites are apparently loaded by contraction of flexor muscles
      when the leg is not in contact with the substratum. Hence the mechanism of a
      transarticular sclerite is more similar to the flight and jumping mechanisms of
      other arthropods than to running vertebrates. The evolutionary significance and
      potential mechanical advantages of the transarticular elastic mechanism are
      discussed.

PMID- 12517995
TI  - Regulation of Na/Pi transporter in the proximal tubule.
AB  - The physiological tuning and pathophysiological alterations of renal proximal
      reabsorption of inorganic phosphate can be ascribed to the net amount of the
      Na/Pi-cotransporter NaPi-IIa localized in the brush border membrane. The net
      amount of NaPi-IIa appears to be the result of an endocytotic rate regulated by a
      complex network of different protein kinases. New approaches demonstrated that
      NaPi-IIa is part of heteromeric protein complexes, organized by PDZ (postsynaptic
      protein PSD95, Drosophila junction protein Disc-large, tight junction protein ZO
      1) proteins. Such complexes are thought to play important roles in the apical
      positioning and regulated endocytosis of NaPi-IIa and therefore such interactions
      have to be considered when explaining proximal phosphate ion reabsorption.

PMID- 12517994
TI  - Expression imbalance map: a new visualization method for detection of mRNA
      expression imbalance regions.
AB  - We describe the development of a new visualization method, called the expression
      imbalance map (EIM), for detecting mRNA expression imbalance regions, reflecting
      genomic losses and gains at a much higher resolution than conventional
      technologies such as comparative genomic hybridization (CGH). Simple spatial
      mapping of the microarray expression profiles on chromosomal location provides
      little information about genomic structure, because mRNA expression levels do not
      completely reflect genomic copy number and some microarray probes would be of low
      quality. The EIM, which does not employ arbitrary selection of thresholds in
      conjunction with hypergeometric distribution-based algorithm, has a high
      tolerance of these complex factors. The EIM could detect regionally
      underexpressed or overexpressed genes (called, here, an expression imbalance
      region) in lung cancer specimens from their gene expression data of
      oligonucleotide microarray. Many known as well as potential loci with frequent
      genomic losses or gains were detected as expression imbalance regions by the EIM.
      Therefore, the EIM should provide the user with further insight into genomic
      structure through mRNA expression.

PMID- 12517996
TI  - Insights into the regulation of gastric acid secretion through analysis of
      genetically engineered mice.
AB  - The regulation of acid secretion in the stomach involves a complex network of
      factors that stimulate secretion in response to the ingestion of a meal and
      maintain homeostasis of gastric pH. Genetically engineered mouse models have
      provided a new opportunity to investigate the importance and function of specific
      molecules and pathways involved in the regulation of acid secretion. Mouse
      mutants with disruptions in the three major stimulatory pathways for acid
      secretion in parietal cells, gastrin, histamine, and acetylcholine, have been
      generated. Disruption of the gastrin pathway results in a major impairment in
      both basal and induced acid secretion. Histamine and acetylcholine pathway
      mutants also have significant alterations in acid secretion, although the
      impairment does not appear to be as severe as in gastrin pathway mutants, perhaps
      due in part to the hypergastrinemia that occurs. Mice with a disruption in the
      somatostatin pathway have increased gastric acid secretion, which confirms an
      important negative regulatory role for this factor. This review discusses these
      genetically engineered mouse models, as well as others, that provide insight into
      the complex regulation of in vivo gastric acid secretion. The regulation of
      growth and cellular morphology of the stomach in these mouse models is also
      presented. In addition, transgene promoters that are expressed in the gastric
      epithelium are discussed because these promoters will be important tools to alter
      cellular physiology in new mouse models in the future.

PMID- 12517997
TI  - The role of exogenous surfactant in the treatment of acute lung injury.
AB  - A number of conditions, such as pneumonia, trauma, or systemic sepsis arising
      from the gut, may result in the acute respiratory distress syndrome (ARDS).
      Because of its significant morbidity and mortality, ARDS has been the focus of
      extensive research. One specific area of interest has been the investigation of
      the role of the surfactant system in the pathophysiology of this disease. Several
      studies have demonstrated that alterations of surfactant contribute to the lung
      dysfunction associated with ARDS, which has led to investigations into the use of
      exogenous surfactant as a therapy for this syndrome. Clinical experience with
      surfactant therapy has been variable owing to a number of factors including the
      nature of the injury at the time of treatment, the specific surfactant
      preparation utilized, the dose and delivery method chosen, the timing of
      surfactant administration over the course of the disease, and the mode of
      ventilation used during and after surfactant administration.

PMID- 12517998
TI  - Second messenger pathways in pulmonary host defense.
AB  - The alveolar macrophage responds to bacterial infection with the production of
      inflammatory mediators that include TNFalpha. Early production of TNFalpha
      results in increased bacterial clearance, whereas too much TNFalpha results in
      many of the hallmarks of bacterial sepsis. TNFalpha production is regulated at
      many levels, including multiple signaling pathways, that lead to transcription,
      translation, and release of functional TNFalpha. Interactions of mitogen
      activated protein (MAP) kinases, lipid signaling pathways, and oxidant-mediated
      mechanisms regulate the response of alveolar macrophages to infection. Animal
      models of sepsis support the central role played by macrophage-derived TNFalpha
      in sepsis.

PMID- 12517999
TI  - Getting ready for the decade of the lipids.

PMID- 12518000
TI  - Dynamics of phosphoinositides in membrane retrieval and insertion.
AB  - The phosphoinositides PtdIns(4,5)P2 and PtdIns(3,4,5)P3 are concentrated in
      plasma membranes of eukaryotic cells, and excluded from endosomes, whereas
      PtdIns(3)P is formed in these latter intracellular membranes and is apparently
      excluded from the plasma membrane. The logic of this asymmetric disposition is
      now revealed by the nature of the effector proteins that selectively bind these
      lipids through specific modules and by the processes that they catalyze.
      PtdIns(3,4,5)P3 has a role in directing exocytosis, in addition to many other
      signaling events, whereas PtdIns(4,5)P2 directs endocytosis through its ability
      to anchor several coat proteins to the plasma membrane. Remarkably, the
      elimination of PtdIns(4,5)P2 from forming endosomes may be required for membrane
      fission to occur. Thus membrane insertion and retrieval can be regulated by
      plasma membrane concentrations of PtdIns(3,4,5)P3 and PtdIns(4,5)P2, whereas
      PtdIns(3)P directs the downstream trafficking and recycling of intracellular
      membranes through its attraction of proteins that catalyze these processes. The
      phosphoinositides thereby control many cell features that depend upon protein
      sorting, including the composition of the plasma membrane itself, which in turn
      determines the cell's responses to its environment.

PMID- 12518001
TI  - Nuclear receptors and the control of metabolism.
AB  - The metabolic nuclear receptors act as metabolic and toxicological sensors,
      enabling the organism to quickly adapt to environmental changes by inducing the
      appropriate metabolic genes and pathways. Ligands for these metabolic receptors
      are compounds from dietary origin, intermediates in metabolic pathways, drugs, or
      other environmental factors that, unlike classical nuclear receptor ligands, are
      present in high concentrations. Metabolic receptors are master regulators
      integrating the homeostatic control of (a) energy and glucose metabolism through
      peroxisome proliferator-activated receptor gamma (PPARgamma); (b) fatty acid,
      triglyceride, and lipoprotein metabolism via PPARalpha, beta/delta, and gamma;
      (c) reverse cholesterol transport and cholesterol absorption through the liver X
      receptors (LXRs) and liver receptor homolog-1 (LRH-1); (d) bile acid metabolism
      through the farnesol X receptor (FXR), LXRs, LRH-1; and (e) the defense against
      xeno- and endobiotics by the pregnane X receptor/steroid and xenobiotic receptor
      (PXR/SXR). The transcriptional control of these metabolic circuits requires
      coordination between these metabolic receptors and other transcription factors
      and coregulators. Altered signaling by this subset of receptors, either through
      chronic ligand excess or genetic factors, may cause an imbalance in these
      homeostatic circuits and contribute to the pathogenesis of common metabolic
      diseases such as obesity, insulin resistance and type 2 diabetes, hyperlipidemia
      and atherosclerosis, and gallbladder disease. Further studies should exploit the
      fact that many of these nuclear receptors are designed to respond to small
      molecules and turn them into therapeutic targets for the treatment of these
      disorders.

PMID- 12518002
TI  - Seeking other disorders within antenatal serum screening programmes for Down's
      syndrome.

PMID- 12518003
TI  - Participation in screening for colorectal cancer based on a faecal occult blood
      test is improved by endorsement by the primary care practitioner.
AB  - OBJECTIVES: To investigate the influence of general practitioner (GP) endorsement
      on participation in screening for colorectal cancer based on a faecal occult
      blood test (FOBT). SETTING: South Australian residents (n=2400), in 1999, aged
      >50 years. METHODS: Random selection of three groups (GP1, GP2, GP3) from two
      general practices and of one group (ER) from the federal electoral roll; n=600
      per group. Without previous communication or publicity, subjects were posted an
      offer of screening by immunochemical FOBT. The GP1 and ER groups were invited
      without indication that their GP was involved; GP2 received an invitation
      indicating support from the practice; and GP3 received an invitation on practice
      letterhead and signed by a practice partner. A reminder was posted at 6 weeks.
      Participation was defined as return of correctly completed FOBT sample cards
      within 12 weeks. RESULTS: Participation rates were: GP1 192/600 (32.0%), GP2
      228/600 (38.0%), and GP3 244/600 (40.7%); chi(2)=10.2, p=0.006. Both GP2 and GP3
      differed significantly from GP1 (odds ratio (OR) 0.77, 95% confidence interval
      (95% CI) 0.60 to 0.98 and relative risk (RR)=0.69, 95% CI 0.54 to 0.87
      respectively). ER (193/600 (32.2%)) and GP1 were not significantly different. Age
      but not sex was significantly associated with participation. Overall test
      positivity rate was 4.6%; five malignancies were found in the 918 who performed
      FOBT. CONCLUSIONS: Association of a GP of recent contact with a screening offer
      in the form of a personalised letter of invitation achieves better participation
      than does the same letter from a centralised screening unit that does not mention
      the GP. Thus, GP enhanced participation is achievable without their actual
      involvement. Additional strategies are needed to further improve participation.

PMID- 12518004
TI  - Programme sensitivity and effectiveness of mammography service screening in
      Helsinki, Finland.
AB  - OBJECTIVES: To evaluate the effectiveness of mammography service screening.
      SETTING: Helsinki (population 0.5 million), the capital of Finland, the breast
      cancer service screening programme was started gradually in 1986. MATERIALS AND
      METHODS: The study was based on the data from the breast cancer screening
      programme in Helsinki. All incident cases of breast cancer and rates in the
      female population in Helsinki during the period 1970-97, and information on the
      subsequent breast cancer mortality were derived from the files of the Finnish
      Cancer Registry. To estimate the sensitivity of the programme, the number of
      screen detected cancers were compared with the overall number of breast cancers
      at the targeted age groups. Effects of screening were estimated for cumulative
      incidence and for the refined mortalities among the birth cohorts screened.
      RESULTS: Altogether 144 400 invitations had been sent during 1986-97 among the 50
      9 year old women as targeted in Helsinki. The average attendance rate was 82%;
      and 545 breast cancers were detected by screening, with a detection rate of
      0.46%. In the birth cohort of women born between the start of 1935 and the end of
      1939-namely, those subjected to most complete screening and long follow up time
      since the onset of the programme-there was an increase in the cumulative
      incidence of breast cancer (relative risk (RR) 1.18, 95% confidence interval (95%
      CI) 1.09 to 1.27). The estimated sensitivity of the screening programme was 58%;
      and 53% if corrected for overdiagnosis. There was also a decrease of 19% (RR
      0.81, 95% CI 0.62 to 1.05) in the refined mortality within this screened birth
      cohort, compared with the death rate of women of comparable ages in the non
      screened reference cohort. CONCLUSION: The study provides further support to the
      hypothesis that service screening with mammography reduces the risk of breast
      cancer mortality.

PMID- 12518005
TI  - All-cause mortality among breast cancer patients in a screening trial: support
      for breast cancer mortality as an end point.
AB  - BACKGROUND: It has recently been suggested that all-cause mortality is a more
      appropriate end point than disease specific mortality in cancer screening trials,
      and that disease specific mortality is biased in favour of screening. This
      suggestion is based partly on supposed inconsistencies between all-cause
      mortality results and disease specific results in cancer screening trials, and
      alleged increases in deaths from causes other than breast cancer among breast
      cancer cases diagnosed among women invited to screening. METHODS: We used data
      from the Swedish Two-County Trial of mammographic screening for breast cancer, in
      which 77 080 women were randomised to an invitation to screening and 55 985 to no
      invitation. We estimated relative risks (RRs) (invited v control) of death from
      breast cancer, death from other causes within the breast cancer cases, and death
      from all causes within the breast cancer cases. RRs were adjusted for age and
      took account of the longer follow up of breast cancer cases in the invited group
      due to lead time. RESULTS: There was a significant 31% reduction in breast cancer
      mortality in the invited group (RR 0.69, 95% confidence interval (CI) 0.58-0.80;
      p<0.001). There was no significant increase in deaths from other causes among
      breast cancer cases in the invited group (RR 1.12, 95% CI 0.96-1.31; p=0.14). A
      significant 19% reduction in deaths from all causes was observed among breast
      cancer cases in the group invited to screening (RR 0.81, 95% CI 0.72-0.90;
      p<0.001). A more conservative estimation gave a significant 13% reduction (RR
      0.87, 95% CI 0.78-0.97; p=0.01). These findings are consistent with the magnitude
      of the reduction in breast cancer mortality. CONCLUSIONS: Invitation to screening
      was associated with a reduction in deaths from all causes among breast cancer
      cases, consistent with high participation rates in screening. There is no
      significant evidence of bias in cause of death classification in the Two-County
      Trial, and as breast cancer mortality is the targeted clinical outcome in breast
      cancer screening, it is the appropriate end point in a breast cancer screening
      trial. All-cause mortality is a poor and inefficient surrogate for breast cancer
      mortality.

PMID- 12518006
TI  - Repeated mammographic screening reduces breast cancer mortality along the
      continuum of age.
AB  - OBJECTIVE: The optimal age boundaries for breast cancer screening are still under
      debate. A case-referent design was used to describe the effect of mammographic
      screening on breast cancer mortality along the continuum of age, based on a 20
      year follow up period. SETTING: The population based breast cancer screening
      programme in Nijmegen, The Netherlands, which has biennially invited women over
      35 years since 1975. METHODS: Cases, defined as women who died from primary
      breast cancer between 1987 and 1997, were selected from the group of women who
      received at least one invitation to the screening programme. For 157 cases, 785
      women from the same group were selected as referents. Information on the index
      screening (the screening examination preceding diagnosis of the case) was
      collected for both cases and referents. The risk of dying from breast cancer was
      calculated per 10 year moving age group for women who had attended the index
      screening versus those who had not. RESULTS: The youngest 10 year age group
      showing an effect in our study were women aged 45-54 at their index screening.
      Breast cancer mortality for women in this group who attended the index screening
      was 32% lower, although not significant, than for women who did not (odds ratio
      (OR) 0.68, 95% confidence interval (95% CI) 0.33 to 1.41). This reduction in risk
      was not explained solely by an effect in women over 50 because the OR in women
      aged 45-49 was 0.56 (95% CI 0.20 to 1.61). Reductions in mortality became smaller
      with increasing age. Nevertheless, for women over 60 at index screening,
      participation in screening over a maximum 4 year period before diagnosis of the
      case yielded protective effects at least up to an age around 80. CONCLUSIONS:
      Although our results are based on a relatively small number of cases, they
      suggest that even in a programme with a 2 year screening interval there may be a
      benefit of starting screening around age 45. Also older women who participate at
      least once every 4 years still have much to gain from screening.

PMID- 12518007
TI  - Monitoring women's experiences during three rounds of breast cancer screening:
      results from a longitudinal study.
AB  - OBJECTIVES: (a) To monitor experiences of women during three successive rounds of
      breast screening; (b) to examine the impact of previous experiences (obtained
      either immediately after the latest mammogram or shortly before the subsequent
      one) on reattendance; and (c) to examine which factors are associated with the
      experience of pain and distress during screening. SETTING: The Dutch Breast
      Cancer Screening Programme METHODS: 2657 women completed a baseline measurement
      (response rate 67%) about 8 weeks after they had been invited for an initial
      mammogram (T(1)). Actual participation data of these women in the second and
      third rounds of screening were collected. Follow up questionnaires were sent to
      subgroups of the sample at different times: shortly before the second screening
      (T(2); response rate 86%), shortly after the second screening (T(3); response
      rate 85%), shortly before the third screening (T(4); response rate 80%), and
      shortly after the third screening (T(5); response rate 78%). RESULTS: Most women
      were satisfied with the first screening round and remained positive about
      subsequent screens. Although pain and anxiety were not uncommon, only a few (10%
      15%) experienced moderate or severe levels of distress or pain. Experiences were
      relatively stable: women who experienced pain in the first screen were more
      likely to experience pain in subsequent screens (r values from 0.39 to 0.50).
      Fear of breast cancer was associated with increased distress related to
      mammography and, to a lesser extent, with increased pain during the mammography.
      Evidence was found for a relief effect: women were more positive about their
      previous screen when asked shortly after this screen, than when asked just before
      the subsequent one. Previous experiences (obtained either proximally or distally)
      were only slightly predictive for future attendance. CONCLUSION: Experiences
      during mammography are fairly stable. Negative experiences were generally not a
      reason to drop out of the programme.

PMID- 12518008
TI  - An investigation into the number of appointment changes and queries arising as a
      result of extending breast screening to older women in the United Kingdom.
AB  - OBJECTIVE: To compare the number of telephone queries and appointment changes
      requested by women aged 65-69 with women aged 50-64. SETTING: Department of
      Health funded demonstration study of extending breast screening to women of 65
      69. METHODS: A survey was conducted for 1 week, each month, over the period of a
      year. Data were collected on the date of the query, the age of the woman, whether
      and why the appointment was changed, and whether the location for screening was
      changed. RESULTS: The proportion of telephone queries or appointment changes was
      significantly more for women aged 50-64 years (p<0.001), 29.7% of women invited
      aged 50-64 compared with 26.5% of women invited aged 65-69. The main reason for
      changing the appointments was inconvenience for both age groups. CONCLUSIONS:
      Administrative costs associated with inviting an older woman for breast screening
      are no more than those for a woman aged 50-64. The number of telephone calls was
      high in both age groups, which has resource implications for extending the breast
      screening programme. The extent of appointment queries or changes needs to be
      considered in the funding of future population screening programmes with
      preallocated appointment systems.

PMID- 12518009
TI  - Estimate of population coverage with the prostate specific antigen (PSA) test to
      screen for prostate cancer in a metropolitan area of northern Italy.
AB  - The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a
      population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was
      examined. Data were drawn from the outpatient database of the local health
      information system. A total of 139 350 PSA tests were used in 83 943 subjects.
      Overall, 26.9% of the male population aged 40 or older, with no history of
      prostate cancer, received a PSA test in the 2 year study period. For subjects
      older than 50 the rate rose to 34%. Results show a high coverage of the male
      population in northern Italy with screening using the PSA test for prostate
      cancer.

PMID- 12518010
TI  - Routine urinalysis of patients in hospital in Lebanon: how worthwhile is it?
AB  - OBJECTIVES: To examine the impact of routine urinalysis at admission on inpatient
      care at a hospital in Lebanon, where physicians perceive it to be a valuable
      diagnostic tool, in a country where preventive services are underdeveloped and
      where the epidemiology of kidney diseases possibly differs from that of the
      western world. SETTING: American University Hospital, a tertiary teaching
      hospital in Beirut, Lebanon. METHODS: A retrospective medical record review of
      all adult patients admitted over 2 weeks to the medicine and surgery wards of the
      American University Hospital. Outcomes measured were frequency of routine
      urinalysis versus urinalysis for a clinical indication, investigation of abnormal
      test results, and implications of test results on clinical management. RESULTS:
      367 (79%) of 462 study patients underwent urinalysis. 266 (73%) patients had
      routine urinalysis. Abnormal results were found in 97(37%) routine tests and 67
      (66%) of those clinically indicated urinalysis (p<0.001). Abnormalities were
      investigated in 21 (22%) of the abnormal routine urinalyses and 45 (67%) of the
      abnormal clinically indicated urinalyses (p<0.001). Logistic regression analysis
      showed no factors to correlate positively with investigation of abnormal
      urinalysis. Treatment was given to two (1%) patients who had had routine
      urinalysis and 26 (26%) of all those tested because of a clinical indication
      (p<0.001). CONCLUSIONS: Clinical response to any abnormal urinalysis is more
      likely when a urine test is done for a clinical indication. In this study
      setting, impact of routine admission urinalysis on patient care was negligible.
      Despite physicians' perception of routine urinalysis being a valuable case
      finding tool, in this study its true value remains questionable.

PMID- 12518011
TI  - What is the risk of mortality for people who are screen positive in a diabetes
      screening programme but who do not have diabetes on biochemical testing? Diabetes
      screening programmes from a public health perspective.
AB  - OBJECTIVES: To assess mortality risk in people classified by the Cambridge risk
      score (CRS), a previously validated simple screening tool for undiagnosed type 2
      diabetes that uses only information routinely available in primary care. SETTING:
      Random sample of the general population between 50 and 75 years of age in Hoorn,
      The Netherlands METHODS: The results of the CRS were compared with the gold
      standard for diabetes, the oral glucose tolerance test (OGTT) results classified
      according to the World Health Organisation (WHO) 1999 diagnostic criteria. Cox's
      proportional hazards regression was used to assess the risk of mortality of
      screen positive and screen negative people. RESULTS: 154 people out of the total
      population of 2297 had previously undiagnosed diabetes and 113 (73%) of these
      would have been detected with the CRS (true positive). However, the CRS
      identified a much larger group (n=1037) who were positive for the score, but who
      did not have diabetes on biochemical testing (false positive). Unadjusted risk of
      mortality was highest in the true positive group (3.40 95% confidence interval
      (95% CI, 2.15 to 5.38)), intermediate in false positive people (2.62 (2.00 to
      3.43)), and lowest in false negative people (1.50 (0.55 to 4.09)) with the true
      negative group as reference. Adjustment for age and sex resulted in similar risk
      estimates for all three groups, but mortality risk was significantly increased
      only in false positive and true positive groups compared with the true negative
      group. CONCLUSIONS: People who have a positive risk score are at high risk of
      mortality whether or not subsequent testing shows them to have diabetes. Direct
      public health interventions in this high risk population may be appropriate.

PMID- 12518014
TI  - Potential biases in Down syndrome birth prevalence estimation.

PMID- 12518017
TI  - The application of computational methods to explore the diversity and structure
      of bacterial fatty acid synthase.
AB  - Acyl carrier protein (ACP) is a central element in the bacterial, type II
      dissociated fatty acid synthase (FAS II) system. ACP delivers the fatty acyl
      intermediates to a variety of enzymes with different biochemical functions and 3
      dimensional (3-D) structures. Computational techniques have proved invaluable in
      guiding the experimental designs that have uncovered the recognition helix on ACP
      and the common features on its target enzymes responsible for specific
      protein*protein interactions. Escherichia coli has been the model organism for
      the study of FAS II, but the availability of complete genomic sequences of a
      growing number of bacteria coupled with computational bioinformatics has led to
      new discoveries on the mechanisms that regulate E. coli FAS II and allowed the
      differences between the E. coli paradigm and major groups of pathogens to be
      identified and experimentally addressed. Computational methods facilitated the
      discovery of the E. coli fatty acid synthesis transcriptional regulator, FabR,
      and led to the identification of novel bacterial FAS II proteins in Gram-positive
      pathogens, including enoyl-ACP reductases (FabK and FabL) and trans-2-cis-3
      decenoyl-ACP isomerase FabM. As more genomic sequences and 3-D coordinates are
      added to the databases, the power and resolution of the computational approaches
      will increase to offer deeper insight into the structure, diversity and function
      of lipid metabolic pathways.

PMID- 12518018
TI  - Caveolins and macrophage lipid metabolism.
AB  - The identification of caveolin-1 more than a decade ago initiated active research
      into its role in the formation of caveolae, membrane trafficking, signal
      transduction pathways, and lipid homeostasis. Although caveolins are ubiquitously
      expressed, the majority of the available information comes from differentiated
      cells rich in caveolins, such as fibroblasts, adipocytes, and endothelial cells.
      During the development of atherosclerosis, macrophages play a pivotal role in the
      formation of the fatty streak lesions. They take up large amounts of lipids and
      accumulate in the subendothelial space, forming foam cells that fill up the
      lesion area. Since caveolins have been implicated in the regulation of cellular
      cholesterol metabolism in several cell types, it is of interest to examine their
      potential function in macrophages. In this review, we attempt to summarize
      current knowledge and views on the role of caveolins in cholesterol metabolism
      with emphasis on macrophages.

PMID- 12518019
TI  - Microsomal triglyceride transfer protein and its role in apoB-lipoprotein
      assembly.
AB  - Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are
      necessary for lipoprotein assembly. ApoB consists of five structural domains,
      betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3). We propose that MTP contains
      three structural motifs (N-terminal beta-barrel, central alpha-helix, and C
      terminal lipid cavity) and three functional domains (lipid transfer, membrane
      associating, and apoB binding). MTP's lipid transfer activity is required for the
      assembly of lipoproteins. This activity renders nascent apoB secretion-competent
      and may be involved in the import of triglycerides into the lumen of endoplasmic
      reticulum. In addition, MTP binds to apoB with high affinity involving ionic
      interactions. MTP interacts at multiple sites in the N-terminal betaalpha(1)
      structural domain of apoB. A novel antagonist that inhibits apoB-MTP binding
      decreases apoB secretion. Furthermore, site-directed mutagenesis and deletion
      analyses that inhibit apoB-MTP binding decrease apoB secretion. Lipids modulate
      protein-protein interactions between apoB and MTP. Lipids associated with MTP
      increase apoB-MTP binding whereas lipids associated with apoB decrease this
      binding. Thus, specific antagonist, site-directed mutagenesis, deletion analyses,
      and modulation studies support the notion that apoB-MTP binding plays a role in
      lipoprotein biogenesis. However, specific steps in lipoprotein assembly that
      require apoB-MTP binding have not been identified. ApoB-MTP binding may be
      important for the prevention of degradation and lipidation of nascent apoB.

PMID- 12518021
TI  - Plasma fatty acids and [13C]linoleic acid metabolism in preterm infants fed a
      formula with medium-chain triglycerides.
AB  - Most preterm infant formulas contain medium-chain triacylglycerols (MCT), but the
      effects of MCT on polyunsaturated fatty acid status and metabolism are
      controversial. Thus, we studied the effects of MCT on linoleic acid metabolism
      using stable isotopes. Enterally fed preterm infants were randomized to receive
      for 7 days 40% of fat as MCT (n = 10) or a formula without MCT (n = 9). At study
      day 5, infants received orally 2 mg/kg body weight of (13)C-labeled linoleic
      acid. Fatty acids in plasma lipid classes and (13)C enrichment of phospholipid
      fatty acids were measured and tracer oxidation was monitored. Compared with the
      control group, the MCT group showed lower breath (13)CO(2) and higher plasma
      triacylglycerol contents of octanoic acid, of decanoic acid, and of total long
      chain polyunsaturated fatty acids (57.1 +/- 4.4 micro mol/l vs. 37.9 +/- 4.8
      micro mol/l, P < 0.01). Concentrations of several polyunsaturated fatty acids in
      plasma phospholipids and non esterified fatty acids were higher in the MCT group.
      (13)C concentrations in phospholipid n-6 fatty acids indicated no difference in
      the relative conversion of linoleic to arachidonic acid. We conclude that oral
      MCT effectively reduce polyunsaturated fatty acid and long chain polyunsaturated
      fatty acid oxidation in preterm infants without compromising endogenous n-6 long
      chain polyunsaturated fatty acid synthesis.

PMID- 12518020
TI  - Cholesteryl ester transfer protein expression attenuates atherosclerosis in
      ovariectomized mice.
AB  - Reduced estrogen levels result in loss of protection from coronary heart disease
      in postmenopausal women. Enhanced and diminished atherosclerosis have been
      associated with plasma levels of cholesteryl ester transfer protein (CETP);
      however, little is known about the role of CETP-ovarian hormone interactions in
      atherogenesis. We assessed the severity of diet-induced atherosclerosis in
      ovariectomized (OV) CETP transgenic mice crossbred with LDL receptor knockout
      mice. Compared with OV CETP expressing ((+)), OV CETP non-expressing ((-)) mice
      had higher plasma levels of total, VLDL-, LDL-, and HDL-cholesterol, as well as
      higher antibodies titers against oxidized LDL. The mean aortic lesion area was 2
      fold larger in OV CETP(-) than in OV CETP(+) mice (147 +/- 90 vs. 73 +/- 42 x
      10(3) micro m(2), respectively). Estrogen therapy in OV mice blunted the CETP
      dependent differences in plasma lipoproteins, oxLDL antibodies, and
      atherosclerosis severity. Macrophages from OV CETP(+) mice took up less labeled
      cholesteryl ether (CEt) from acetyl-LDL than macrophages from OV CETP(-) mice.
      Estrogen replacement induced a further reduction in CEt uptake and an elevation
      in HDL mediated cholesterol efflux from pre-loaded OV CETP(+) as compared with OV
      CETP(-) macrophages. These findings support the proposed anti-atherogenic role of
      CETP in specific metabolic settings.

PMID- 12518022
TI  - In vivo investigation of the placental transfer of (13)C-labeled fatty acids in
      humans.
AB  - Placental fatty acid transfer in humans in vivo was studied using stable
      isotopes. Four pregnant women undergoing cesarean section received 4 h before
      delivery an oral dose of [(13)C]palmitic acid (PA), [(13)C]oleic acid (OA),
      [(13)C]linoleic acid (LA), and [(13)C]docosahexaenoic acid (DHA). Maternal blood
      samples were collected at -4 h (basal), -3 h, -2 h, -1 h, 0 h, and +1 h relative
      to time of cesarean section. At the time of birth, venous cord blood and
      placental tissue were collected. Fatty acid composition was determined by gas
      liquid chromatography and isotopic enrichment by gas chromatography-combustion
      isotope ratio mass spectrometry. (13)C-enrichment of fatty acids in the
      nonesterified fatty acids (NEFA) of cord plasma tended to be higher than in NEFA
      of placenta, with statistically significant differences for the nonesterified OA
      and DHA ([(13)C]PA, 0.024 +/- 0.011 vs. 0.001 +/- 0.001; [(13)C]OA, 0.042 +/-
      0.008 vs. 0.005 +/- 0.003; [(13)C]LA, 0.038 +/- 0.010 vs. 0.008 +/- 0.002;
      [(13)C]DHA, 0.059 +/- 0.009 vs. 0.010 +/- 0.003). The ratio of tracer fatty acid
      concentrations of placenta to maternal plasma was significantly higher for
      [(13)C]DHA than for the other fatty acids ([(13)C]PA, 7.1 +/- 1%; [(13)C]OA, 3.8
      +/- 0.4%; [(13)C]LA, 9.2 +/- 1.3%; [(13)C]DHA, 25.9 +/- 3.4%). These results
      suggest that only a part of the placental NEFA participated in fatty acid
      transfer, and that the placenta showed a preferential accretion of DHA relative
      to the other fatty acids.

PMID- 12518023
TI  - Apoptosis induced by clofibrate in Yoshida AH-130 hepatoma cells: role of HMG-CoA
      reductase.
AB  - Clofibrate is a hypolipidemic drug belonging to the peroxisome proliferator (PP)
      family. PPs are well-recognized hepatocarcinogens, though only for rodents and
      not for humans. Their oncogenicity is usually ascribed to mitogenic or
      antiapoptotic action. However, we have reported that clofibrate can trigger fast
      and extensive apoptosis in rodent and human tumor cell lines. The present study
      examines the possible mechanisms involved in clofibrate-induced apoptosis in AH
      130 hepatoma cells. The results show that the apoptogenic effect of clofibrate
      does not depend on induction of peroxisome proliferator activated receptors
      (PPARs), but on interference with HMG-CoA reductase (HMGR), a key enzyme that
      regulates cholesterol biosynthesis and production of isoprenoid units for protein
      farnesylation. The level and activity of HMGR mRNA are reduced in clofibrate
      treated AH-130 cells and apoptosis can be partially prevented by addition of
      mevalonate. Moreover, cholesterol and cholesterol ester content decreases early
      in mitochondria, and cytocrome c is released in the cytosol. On the contrary,
      perturbations at the level of protein farnesylation are not important in
      determining the fast apoptogenic effect, since treatment of AH-130 cells with an
      inhibitor of farnesyltransferase induces apoptosis only after 4 h. In conclusion,
      inhibition of HMGR and decreased cholesterol content are crucial events in
      clofibrate-induced apoptosis in AH-130 hepatoma cells.

PMID- 12518024
TI  - Biomimetic lipid/polymer colorimetric membranes: molecular and cooperative
      properties.
AB  - Characterization of membranes and of biological processes occurring within
      membranes is essential for understanding fundamental cellular behavior. Here we
      present a detailed biophysical study of a recently developed colorimetric
      biomimetic membrane assembly constructed from physiological lipid molecules and
      conjugated polydiacetylene. Various analytical techniques have been applied to
      characterize the organization of the lipid components in the chromatic vesicles
      and their contributions to the observed blue-to-red color transitions.
      Experiments reveal that both the polymerized units as well as the lipids exhibit
      microscopic phases and form domains whose properties and bilayer organization are
      interdependent. These domains are interspersed within mixed lipid/polymer
      vesicles that have a size distribution different from those of aggregates of the
      individual molecular constituents. The finding that fluidity changes induced
      within the lipid domains are correlated with the chromatic transitions
      demonstrates that the colorimetric platform can be used to evaluate the effects
      of individual molecular components, such as negatively charged lipids and
      cholesterol, upon membrane fluidity and thermal stability.

PMID- 12518025
TI  - ACBP and cholesterol differentially alter fatty acyl CoA utilization by
      microsomal ACAT.
AB  - Microsomal acyl CoA:cholesterol acyltransferase (ACAT) is stimulated in vitro
      and/or in intact cells by proteins that bind and transfer both substrates,
      cholesterol, and fatty acyl CoA. To resolve the role of fatty acyl CoA binding
      independent of cholesterol binding/transfer, a protein that exclusively binds
      fatty acyl CoA (acyl CoA binding protein, ACBP) was compared. ACBP contains an
      endoplasmic reticulum retention motif and significantly colocalized with acyl-CoA
      cholesteryl acyltransferase 2 (ACAT2) and endoplasmic reticulum markers in L-cell
      fibroblasts and hepatoma cells, respectively. In the presence of exogenous
      cholesterol, ACAT was stimulated in the order: ACBP > sterol carrier protein-2
      (SCP-2) > liver fatty acid binding protein (L-FABP). Stimulation was in the same
      order as the relative affinities of the proteins for fatty acyl CoA. In contrast,
      in the absence of exogenous cholesterol, these proteins inhibited microsomal
      ACAT, but in the same order: ACBP > SCP-2 > L-FABP. The extracellular protein BSA
      stimulated microsomal ACAT regardless of the presence or absence of exogenous
      cholesterol. Thus, ACBP was the most potent intracellular fatty acyl CoA binding
      protein in differentially modulating the activity of microsomal ACAT to form
      cholesteryl esters independent of cholesterol binding/transfer ability.

PMID- 12518026
TI  - Physiological characteristics of allo-cholic acid.
AB  - The physiological characterstics of allo-cholic acid (ACA), a typically fetal
      bile acid that reappears during liver regeneration and carcinogenesis were
      investigated. [(14)C] Tauro-ACA (TACA) uptake by Chinese hamster ovary cells
      expressing rat organic anion transporter polypeptide (Oatp)1 or sodium
      taurocholate cotransporter polypeptide (Ntcp) was lower than that of
      [(14)C]taurocholic acid (TCA). Although TACA inhibited ATP-dependent TCA
      transport across plasma membrane vesicles from Sf9 cells expressing rat or mouse
      bile salt export pump (Bsep), no ATP-dependent TACA transport was found. In rats,
      TACA was secreted into bile with no major biotransformation and it had lower
      clearance and longer half-life than TCA. In mice, TACA bile output was lower (
      50%) than that of TCA, whereas TACA induced 9-fold higher bile flow than TCA.
      Even though the intracellular levels were lower for TACA, translocation into the
      hepatocyte nucleus was higher for TACA than for TCA; however, rate of DNA
      synthesis, expression levels of alpha-fetoprotein, albumin, Ntcp, and Bsep, cell
      viability, and apoptosis in rat hepatocytes were similarly affected by both
      isomers. In conclusion, TACA partly shares hepatocellular uptake system(s) for
      TCA. Furthermore, in contrast to other "flat" bile acids, TACA is efficiently
      secreted into bile via transport system(s) other than Bsep and is highly
      choleretic, hence its appearance during certain situations may prevent
      accumulation of cholestatic precursors.

PMID- 12518027
TI  - Sphingosylphosphorylcholine is upregulated in the stratum corneum of patients
      with atopic dermatitis.
AB  - To clarify the functional relevance of sphingomyelin (SM) deacylase to the
      ceramide deficiency seen in atopic dermatitis (AD), we developed a new highly
      sensitive method and measured the metabolic intermediate
      sphingosylphosphorylcholine (SPC) that accumulates in the stratum corneum. SPC in
      intercellular lipids extracted from stratum corneum was reacted with
      [(14)C]acetic anhydride to yield [(14)C-C(2)]SM, which was then analyzed by TLC.
      In both the lesional and non-lesional stratum corneum obtained from patients with
      AD, there was a significant increase in the content of SPC over that of healthy
      control subjects. There was a reciprocal relationship between increases in SPC
      and decreases in ceramide levels of stratum corneum obtained from healthy
      controls, and from lesional and non-lesional skin from patients with AD.
      Comparison with other sphingolipids present in the stratum corneum demonstrated
      that there is a significant positive correlation between SPC and
      glucosylsphingosine, another lysosphingolipid derived from glucosylceramide by
      another novel epidermal enzyme, termed glucosylceramide deacylase. In contrast,
      there was no correlation between SPC and sphingosine, a degradative product
      generated from ceramide by ceramidase. These findings strongly suggest the
      physiological relevance of SM deacylase function in vivo to the ceramide
      deficiency found in the skin of patients with AD.

PMID- 12518029
TI  - Brain lipid metabolism in the cPLA2 knockout mouse.
AB  - We examined brain phospholipid metabolism in mice in which the cytosolic
      phospholipase A(2) (cPLA(2,) Type IV, 85 kDa) was knocked out (cPLA(2)(-/-)
      mice). Compared with controls, these mice demonstrated altered brain
      concentrations of several phospholipids, reduced esterified linoleate,
      arachidonate, and docosahexaenoate in choline glycerophospholipid, and reduced
      esterified arachidonate in phosphatidylinositol. Unanesthetized cPLA(2)(-/-) mice
      had reduced rates of incorporation of unlabeled arachidonate from plasma and from
      the brain arachidonoyl-CoA pool into ethanolamine glycerophospholipid and choline
      glycerophospholipid, but elevated rates into phosphatidylinositol. These
      differences corresponded to altered turnover and metabolic loss of esterified
      brain arachidonate. These results suggests that cPLA(2) is necessary to maintain
      normal brain concentrations of phospholipids and of their esterified
      polyunsaturated fatty acids. Reduced esterified arachidonate and docosahexaenoate
      may account for the resistance of the cPLA(2)(-/-) mouse to middle cerebral
      artery occlusion, and should influence membrane fluidity, neuroinflammation,
      signal transduction, and other brain processes.

PMID- 12518028
TI  - The effects of protease inhibitors on basal and insulin-stimulated lipid
      metabolism, insulin binding, and signaling.
AB  - The objective of our research was to investigate the effects of the protease
      inhibitors ritonavir, saquinavir, and indinavir on triglyceride synthesis,
      lipolysis, insulin binding, and signaling in differentiating 3T3 L1 pre
      adipocytes. Saquinavir, ritonavir, and indinavir all stimulated triglyceride (TG)
      synthesis. Additionally, all concentrations of protease inhibitors employed
      (i.e., 0.1 micro M to 10 micro M) significantly decreased insulin-stimulated TG
      synthesis. No effects of any of the protease inhibitors were observed either on
      basal lipolysis or after stimulation of lipolysis with 100 nM noradrenaline.
      Specific (125)I-insulin binding was observed to be decreased by exposure to all
      the protease inhibitors throughout the period of adipocyte phenotype development.
      This was mediated by indinavir through a receptor decrease and had no effect on
      receptor affinity. During differentiation with ritonavir (i.e., 1-11 days post
      addition of differentiating cocktail), insulin receptor substrate-1 (IRS-1)
      tyrosine phosphorylation was ascertained (day 11) and found to be decreased in
      the ritonavir exposed cells when compared with control cells. The results
      reported herein demonstrate protease inhibitor effects on basal TG synthesis
      while exhibiting decreased insulin-stimulated TG synthesis at physiological
      concentrations of protease inhibitors. These effects may be subsequent to
      decreased insulin binding and/or IRS-1 tyrosine phosphorylation.

PMID- 12518030
TI  - Impact of mitochondrial beta-oxidation in fatty acid-mediated inhibition of
      glioma cell proliferation.
AB  - Tetradecylthioacetic acid (TTA), which cannot be beta-oxidized, exerts growth
      limiting properties in glioma cells. In order to investigate the importance of
      modulated lipid metabolism and alterations in mitochondrial properties in this
      cell death process, we incubated glioma cells both with TTA and the oxidizable
      fatty acid palmitic acid (PA), in the presence of L-carnitine and the carnitine
      palmitoyltransferase inhibitors etomoxir and aminocarnitine. L-carnitine partly
      abolished the PA-mediated growth reduction of glioma cells, whereas etomoxir and
      aminocarnitine enhanced the antiproliferative effect of PA. The production of
      acid-soluble products increased and the incorporation of PA into glycerolipids
      decreased after L-carnitine supplementation. L-carnitine was found to enhance the
      antiproliferative effect of TTA, but did not affect the incorporation of TTA into
      glycerolipids, or ceramide. PDMP, sphingosine 1-phosphate, desipramine, fumonisin
      B(1), and L-cycloserine were able not to rescue the glioma cells from PA and TTA
      induced growth inhibition, suggesting that increased ceramide production is not
      important in the growth reduction. TTA-mediated growth inhibition was accompanied
      with an increased uptake of PA and increased incorporation of PA into
      triacylglycerol (TG). Our data suggest that mitochondrial functions are involved
      in fatty acid-mediated growth inhibition. Whether there is a causal relationship
      between TG accumulation and the apoptotic process remains to be determined.

PMID- 12518031
TI  - Squalene synthase inhibitors suppress triglyceride biosynthesis through the
      farnesol pathway in rat hepatocytes.
AB  - We recently demonstrated that squalene synthase (SQS) inhibitors reduce plasma
      triglyceride through an LDL receptor-independent mechanism in Watanabe heritable
      hyperlipidemic rabbits (Hiyoshi et al. 2001. Eur. J. Pharmacol. 431: 345-352).
      The present study deals with the mechanism of the inhibition of triglyceride
      biosynthesis by the SQS inhibitors ER-27856 and RPR-107393 in rat primary
      cultured hepatocytes. Atorvastatin, an HMG-CoA reductase inhibitor, had no effect
      on triglyceride biosynthesis, but reversed the inhibitory effect of the SQS
      inhibitors. A squalene epoxidase inhibitor, NB-598, affected neither triglyceride
      biosynthesis nor its inhibition by ER-27856 and RPR-107393. The reduction of
      triglyceride biosynthesis by ER-27856 and RPR-107393 was potentiated by
      mevalonolactone supplementation. Treatment of hepatocytes with farnesol and its
      derivatives reduced triglyceride biosynthesis. In addition, we found that ER
      27856 and RPR-107393 significantly reduced the incorporation of [1-(14)C]acetic
      acid into oleic acid, but not the incorporation of [1-(14)C]oleic acid into
      triglyceride. Though ER-27856 and RPR-107393 increased mitochondrial fatty acid
      beta-oxidation, the inhibition of beta-oxidation by RS-etomoxir had little effect
      on their inhibition of triglyceride biosynthesis. These results suggest that SQS
      inhibitors reduce triglyceride biosynthesis by suppressing fatty acid
      biosynthesis via an increase in intracellular farnesol and its derivatives.

PMID- 12518032
TI  - Regulation of the angiopoietin-like protein 3 gene by LXR.
AB  - Angiopoietins are members of the vascular endothelial growth factor family. One
      family member, angiopoietin-like protein 3 (Angptl3), was recently shown to be
      predominantly expressed in the liver and to play an important role in regulating
      lipid metabolism. In this study, we show that the Angptl3 gene is a direct target
      of the liver X receptor (LXR). Mice fed a high cholesterol diet exhibited a
      significant increase in Angptl3 expression in the liver. Oral administration to
      mice of T0901317, a synthetic LXR-selective agonist, increases levels of plasma
      lipids and Angptl3 mRNA in the liver. Treatment of HepG2 cells with LXR selective
      agonists led to a dose-dependent increase of Angptl3 mRNA. Analysis of the DNA
      sequence just 5' of the Angptl3 transcriptional start site revealed the presence
      of several potential transcription factor binding sites, including that for LXR.
      When transfected into HepG2 cells, the promoter activity of Angptl3 was
      significantly induced by LXR- or retinoid X receptor-selective agonists. Mutation
      of the predicted LXR binding site (DR4 element) completely abolished the LXR
      agonist-mediated activation of the promoter. Together, these studies show that
      Angptl3 is transcriptionally regulated by LXR, and reveals a novel mechanism by
      which LXR may regulate lipid metabolism.

PMID- 12518034
TI  - Expression of human hormone-sensitive lipase in white adipose tissue of
      transgenic mice increases lipase activity but does not enhance in vitro
      lipolysis.
AB  - Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and
      cholesteryl esters (CEs). The enzyme is highly expressed in adipose tissues
      (ATs), where it is thought to play an important role in fat mobilization. The
      purpose of the present work was to study the effect of a physiological increase
      of HSL expression in vivo. Transgenic mice were produced with a 21 kb human
      genomic fragment encompassing the exons encoding the adipocyte form of HSL. hHSL
      mRNA was expressed at 3-fold higher levels than murine HSL mRNA in white
      adipocytes. Transgene expression was also observed in brown adipose tissue (BAT)
      and skeletal muscle. The human protein was detected in ATs of transgenic (Tg)
      mice. The hydrolytic activities against triacylglycerol (TG), diacylglycerol (DG)
      analog, and CE were increased in transgenic mouse AT. However, cAMP-inducible
      adipocyte lipolysis was lower in transgenic animals. In the B6CBA genetic
      background, transgenic mice up to 14 weeks of age showed lower body weight and
      fat mass. The phenotype was not observed in older animals and in mice fed a high
      fat diet (HFD). In the OF1 genetic background, there was no difference in fat
      mass of mice fed ad libitum. However, transgenic mice became leaner than their
      wild-type (WT) littermates after a 4 day calorie restriction. The data show that
      overexpression of HSL, despite increased lipase activity, does not lead to
      enhanced lipolysis.

PMID- 12518033
TI  - Mechanisms of liver steatosis in rats with systemic carnitine deficiency due to
      treatment with trimethylhydraziniumpropionate.
AB  - Rats with systemic carnitine deficiency induced by treatment with
      trimethylhydraziniumpropionate (THP) develop liver steatosis. This study aims to
      investigate the mechanisms leading to steatosis in THP-induced carnitine
      deficiency. Rats were treated with THP (20 mg/100 g) for 3 or 6 weeks and were
      studied after starvation for 24 h. Rats treated with THP had reduced in vivo
      palmitate metabolism and developed mixed liver steatosis at both time points. The
      hepatic carnitine pool was reduced in THP-treated rats by 65% to 75% at both time
      points. Liver mitochondria from THP-treated rats had increased oxidative
      metabolism of various substrates and of beta-oxidation at 3 weeks, but reduced
      activities at 6 weeks of THP treatment. Ketogenesis was not affected. The hepatic
      content of CoA was increased by 23% at 3 weeks and by 40% at 6 weeks in THP
      treated rats. The cytosolic content of long-chain acyl-CoAs was increased and the
      mitochondrial content decreased in hepatocytes of THP treated rats, compatible
      with decreased activity of carnitine palmitoyltransferase I in vivo. THP-treated
      rats showed hepatic peroxisomal proliferation and increased plasma VLDL
      triglyceride and phospholipid concentrations at both time points. A reduction in
      the hepatic carnitine pool is the principle mechanism leading to impaired hepatic
      fatty acid metabolism and liver steatosis in THP-treated rats. Cytosolic
      accumulation of long-chain acyl-CoAs is associated with increased plasma VLDL
      triglyceride, phospholipid concentrations, and peroxisomal proliferation.

PMID- 12518035
TI  - Ethanolamine plasmalogens prevent the oxidation of cholesterol by reducing the
      oxidizability of cholesterol in phospholipid bilayers.
AB  - The aims of the present study are to establish an appropriate system for
      assessing the oxidizability of cholesterol (CH) in phospholipid (PL) bilayers,
      and to explore the effect of ethanolamine plasmalogens on the oxidizability of CH
      with the system, through comparing with those of choline plasmalogens,
      phosphatidylethanolamine, and antioxidant alpha-tocopherol (Toc). Investigation
      of the effects of oxidants, vesicle lamellar forms, saturation level, and
      constituent ratio of PLs in vesicles on CH oxidation revealed the suitability of
      a system comprising unilamellar vesicles and the water-soluble radical initiator
      2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH). As CH oxidation in the
      system was found to follow the rate law for autoxidation without significant
      interference from oxidizable PLs, the oxidizability of CH in PL bilayers could be
      experimentally determined from the equation: k (p)/(2k (t))(1/2)=R
      (p)/[LH]R(i)(1/2) by measuring the rate of CH oxidation. It was found with this
      system that bovine brain ethanolamine plasmalogen (BBEP), bovine heart choline
      plasmalogen, and egg yolk phosphatidylethanolamine lower the oxidizability of CH
      in bilayers. Comparison of the dose-dependent effects of each PL demonstrated the
      greatest ability of BBEP to reduce the oxidizability. A time course study of CH
      oxidation suggested a novel mechanism of BBEP for lowering the oxidizability of
      CH besides the action of scavenging radicals.

PMID- 12518036
TI  - Sterol effects and sites of sterol accumulation in Caenorhabditis elegans:
      developmental requirement for 4alpha-methyl sterols.
AB  - Caenorhabditis elegans requires sterol, usually supplied as cholesterol, but this
      is enzymatically modified, and different sterols can substitute. Sterol
      deprivation decreased brood size and adult growth in the first generation, and
      completely, reversibly, arrested growth as larvae in the second. After one
      generation of sterol deprivation, 10 ng/ml cholesterol allowed delayed laying of
      a few eggs, but full growth required 300 ng/ml. C. elegans synthesizes two
      unusual 4alpha-methyl sterols (4MSs), but each 4MS supported only limited growth
      as the sole sterol. However, addition of only 10 ng of cholesterol to 1,000 ng of
      4MS restored full growth and egg-laying, suggesting that both a 4MS and an
      unmethylated sterol are required for development. Filipin stained sterols in only
      a few specific cells: the excretory gland cell, two amphid socket cells, two
      phasmid socket cells and, in males, spicule socket cells. Sterols were also
      present in the pharynx and in the intestine of feeding animals in a proximal-to
      distal gradient. This non-random sterol distribution, the low concentration
      requirements, and the effects of 4MSs argues that sterols are unlikely to be used
      for bulk structural modification of cell membranes, but may be required as
      hormone precursors and/or developmental effectors.

PMID- 12518037
TI  - Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport.
AB  - Plasmalogens are a major sub-class of ethanolamine and choline phospholipids in
      which the sn-1 position has a long chain fatty alcohol attached through a vinyl
      ether bond. These phospholipids are proposed to play a role in membrane fusion
      mediated events. In this study, we investigated the role of the ethanolamine
      plasmalogen plasmenylethanolamine (PlsEtn) in intracellular cholesterol transport
      in Chinese hamster ovary cell mutants NRel-4 and NZel-1, which have single gene
      defects in PlsEtn biosynthesis. We found that PlsEtn was essential for specific
      cholesterol transport pathways, those from the cell surface or endocytic
      compartments to acyl-CoA/cholesterol acyltransferase in the endoplasmic
      reticulum. The movement of cholesterol from the endoplasmic reticulum or
      endocytic compartments to the cell surface was normal in PlsEtn-deficient cells.
      Also, vesicle trafficking was normal in PlsEtn-deficient cells, as measured by
      fluid phase endocytosis and exocytosis, as was the movement of newly-synthesized
      proteins to the cell surface. The mutant cholesterol transport phenotype was due
      to the lack of PlsEtn, since it was corrected when NRel-4 cells were transfected
      with a cDNA encoding the missing enzyme or supplied with a metabolic intermediate
      that enters the PlsEtn biosynthetic pathway downstream of the defect. Future work
      must determine the precise role that plasmalogens have on cholesterol transport
      to the endoplasmic reticulum.

PMID- 12518038
TI  - Efficiency of intestinal cholesterol absorption in humans is not related to apoE
      phenotype.
AB  - The present study investigated the role of apolipoprotein E (apoE) phenotype on
      intestinal cholesterol absorption and cholesterol synthesis. Studies were carried
      out in eight subjects homozygous for the apoE4 and 12 subjects homozygous for the
      E2 allele (six normocholesterolemic volunteers and six patients with type III
      hyperlipoproteinemia). Cholesterol absorption did not differ between the three
      groups of subjects and averaged 38 +/- 2% (mean +/- SEM) in normolipemic E2/2, 37
      +/- 4% in type III hyperlipemic E2/2, and 41 +/- 3% in E4/4 subjects,
      respectively. Dietary intake of fat and cholesterol had no influence on
      cholesterol absorption efficiency. A positive correlation between efficiency of
      cholesterol absorption and the ratio of campesterol to cholesterol in plasma, an
      indirect marker for cholesterol absorption, was observed after combining the
      results of the three groups (r = 0.504; P < 0.02). Bile acid and total
      cholesterol synthesis were also not affected by the different apoE alleles, but
      the well-known relationship between body weight and cholesterol synthesis was
      noticed (r = 0.574; P < 0.01). Thus, the present study provides evidence that the
      efficiency of intestinal absorption and synthesis of cholesterol in humans are
      not related to the apoE phenotype.

PMID- 12518039
TI  - Discordant expression of the sterol pathway in lens underlies simvastatin-induced
      cataracts in Chbb: Thom rats.
AB  - Simvastatin rapidly induced cataracts in young Chbb:Thom (CT) but not Sprague
      Dawley (SD) or Hilltop Wistar (HW) rats. Oral treatment for 14 but not 7 days
      committed CT rat lenses to cataract formation. The cholesterol to phospholipid
      molar ratio in lenses of treated CT rats was unchanged. Differences between
      strains in serum and ocular humor levels of simvastatin acid poorly correlated
      with susceptibility to cataracts. No significant differences were found between
      rat strains in the capacity of simvastatin acid to inhibit lens-basal sterol
      synthesis. Prolonged treatment with simvastatin comparably elevated HMG-CoA
      reductase protein and enzyme activity in lenses of both cataract resistant and
      sensitive strains. However, in contrast to SD and HW rats, where sterol synthesis
      was markedly increased, sterol synthesis in CT rat lenses remained at baseline.
      Discordant expression of sterol synthesis in CT rats may be due to inadequate
      upregulation of lens HMG-CoA synthase. HMG-CoA synthase protein levels, and to a
      much lesser extent mRNA levels, increased in lens cortex of SD but not CT rats.
      Because upregulation of the sterol pathway may result in increased formation of
      isoprene-derived anti-inflammatory substances, failure to upregulate the pathway
      in CT rat lenses may reflect an attenuated compensatory response to injury that
      resulted in cataracts.

PMID- 12518040
TI  - Non-denaturing polyacrylamide gradient gel electrophoresis for the diagnosis of
      dysbetalipoproteinemia.
AB  - Dysbetalipoproteinemia, an uncommon but highly atherogenic mixed hyperlipidemia
      due to the accumulation of remnants of triglyceride-rich lipoproteins, is
      characterized by cholesterol-enriched VLDL that migrates in the beta-position on
      agarose gels. The demonstration of a broad beta-band on agarose gel
      electrophoresis of plasma is an insensitive method and ultracentrifugation is an
      impractical method of diagnosing this condition. Non-denaturing polyacrylamide
      gradient gel electrophoresis (PGGE) was investigated as a screening method for
      the diagnosis of dysbetalipoproteinemia. A minigel procedure separating the Sudan
      Black prestained apolipoprotein B (apoB)-containing lipoproteins on a 2-8%
      polyacrylamide gel at 4 degrees C overnight was analyzed for ultracentrifugally
      and genetically proven dysbetalipoproteinemic subjects as well as matched
      controls for mixed hyperlipidemia. Visual inspection revealed that the presence
      of only small VLDL- and IDL-like particles in untreated patients was highly
      sensitive (72%) and specific (95%) for dysbetalipoproteinemia. Videodensitometric
      analysis of area under the curve for large and small VLDL, as well as IDL and
      LDL, permitted even better discrimination in subjects whose profiles included
      some staining in the LDL-like region. A ratio of area under the curve of more
      than 0.5 for IDL-LDL allowed for a specificity of 100% and a sensitivity of 89%
      for the diagnosis of dysbetalipoproteinemia. This modified PGGE system may be
      useful in screening for dysbetalipoproteinemia.

PMID- 12518041
TI  - Aminopropyl solid phase extraction and 2 D TLC of neutral glycosphingolipids and
      neutral lysoglycosphingolipids.
AB  - Methods for isolation of neutral lysoglycosphingolipids (n-lyso-GSLs) such as
      glucosylsphingosine and galactosylsphingosine normally involve mild alkaline or
      acid hydrolysis followed by multiple chromatography steps, yielding relatively
      low recoveries of n-lyso-GSLs and neutral glycosphingolipids (n-GSLs). We now
      describe a new technique for isolating these compounds using one chromatography
      step, resulting in quantitative recovery of n-GSLs and n-lyso-GSLs. Lipids are
      extracted using a modified Folch procedure in which recovery is optimized by
      reextracting the Folch upper phase with water-saturated butanol. The extract is
      applied to an aminopropyl solid phase column from which both n-GSLs and n-lyso
      GSLs elute in the same fraction. Separation is achieved using a new two
      dimensional thin-layer chromatography procedure. The usefulness of this technique
      for biological samples was tested by examining Glc[4,5-(3)H]ceramide and Glc[4,5
      (3)H]sphingosine accumulation in metabolically-labeled neurons treated with an
      inhibitor of lysosomal glucocerebrosidase. Accurate quantification of both lipids
      was obtained with Glc[4,5-(3)H]ceramide and Glc[4,5-(3)H]sphingosine accumulating
      at levels of 20 nmol/mg DNA and 40 pmol/mg DNA, respectively. This simple and
      rapid technique can therefore be used for the analysis of lyso-GSLs and GSLs in
      the same tissue, which may permit the determination of their metabolic pathways
      in normal and in pathological tissues, such as those taken from Gaucher and
      Krabbe's disease patients.

PMID- 12518042
TI  - 2002: signaling breakthroughs of the year.

PMID- 12518043
TI  - GAF domains: cyclic nucleotides come full circle.
AB  - Cyclic nucleotides are ubiquitous signaling molecules that are present in life
      forms ranging from bacteria to yeast to humans. In higher eukaryotes, conserved
      molecular machinery processes signals through both cyclic adenosine monophosphate
      (AMP) and cyclic guanosine monophosphate (GMP). Hurley describes how one
      widespread cyclic nucleotide recognition module, the GAF (cyclic GMP, adenylyl
      cyclase, FhlA) domain, formerly thought to bind only cyclic GMP, has now been
      found to bind cyclic AMP as well. Recent structural analysis of a cyclic GMP
      binding GAF domain shows how conserved elements among the cyclic nucleotide
      binding subgroup of GAF domains recognize the common chemical moieties in the two
      compounds.

PMID- 12518044
TI  - Cloud cover limits net CO2 uptake and growth of a rainforest tree during tropical
      rainy seasons.
AB  - Recent global-scale analyses indicate that climate variability affects net carbon
      storage but regard temperature and precipitation to be the main contributors.
      Seasonal and interannual variation in light availability may also limit CO(2)
      uptake. As an experimental test of light limitation by cloud cover during
      tropical rainy seasons and by the unusually heavy cloud cover associated with La
      Nina, we installed high-intensity lamps above the forest canopy to augment light
      for Luehea seemannii, a tropical canopy tree species, during cloudy periods of
      1999-2000. Light augmentation only partially compensated for the reduction in
      photosynthetic photon flux density caused by clouds. Nonetheless, leaves
      acclimated to the augmented irradiance, and photosynthesis, vegetative growth,
      and reproduction increased significantly. Light, rather than water, temperature,
      or leaf nitrogen, was the primary factor limiting CO(2) uptake during the rainy
      season.

PMID- 12518045
TI  - Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels.
AB  - The Na+/K+ pump is a ubiquitous P-type ATPase that binds three cytoplasmic Na+
      ions deep within its core where they are temporarily occluded before being
      released to the extracellular surface. The 3Na+/2K+ -exchange transport cycle is
      completed when two extracellular K+ ions bind and become temporarily occluded
      within the protein and subsequently released to the cytoplasm. Coupling of Na+ 
      ion occlusion to phosphorylation of the pump by ATP and of K+ -ion occlusion to
      its dephosphorylation ensure the vectorial nature of net transport. The occluded
      ion conformations, with binding sites inaccessible from either side, represent
      intermediate states in these alternating-access descriptions of transport. They
      afford protection against potentially catastrophic effects of inadvertently
      allowing simultaneous access from both membrane sides. The marine toxin,
      palytoxin, converts Na+/K+ pumps into nonselective cation channels, possibly by
      disrupting the normal strict coupling between opening of one access pathway in
      the Na+/K+ ATPase and closing of the other. We show here that gating of the
      channels in palytoxin-bound Na+/K+ pumps in excised membrane patches is modulated
      by the pump's physiological ligands: cytoplasmic application of ATP promotes
      opening of the channels, and extracellular replacement of Na+ ions by K+ ions
      promotes closing of the channels. This suggests that, despite the presence of
      bound palytoxin, certain partial reactions of the normal Na+/K+ -transport cycle
      persist and remain capable of effecting the conformational changes that control
      access to the pump's cation-binding sites. These findings affirm the alternating
      access model of ion pumps and offer the possibility of examining ion
      occlusion/deocclusion reactions in single pump molecules.

PMID- 12518046
TI  - Identification of a PU.1-IRF4 protein interaction surface predicted by chemical
      exchange line broadening.
AB  - Relaxation values reflecting residue-specific line broadening revealed amino
      acids in the DNA-binding domain of PU.1 on a surface potentially involved in
      protein-protein interactions. Mutation of these amino acids did not cause protein
      unfolding but destabilized PU.1-DNA binding. Addition of IFN response factor 4 to
      form the ternary complex recovered binding stability. Fluorescence quenching
      experiments proved that this surface of PU.1 interacts with IFN response factor 4
      during binding. Our results provide evidence that residues that display increased
      conformational exchange can be used to predict areas of protein-protein
      interactions.

PMID- 12518047
TI  - Urochordates and the origin of natural killer cells: identification of a CD94/NKR
      P1-related receptor in blood cells of Botryllus.
AB  - Transplantation immunity based on the recognition of MHC molecules is well
      described in vertebrates. Vertebrates, however, do not undergo transplantation
      reaction naturally. The phylogenetically closest group in which transplantation
      reactions can occur is the Urochordata. Therefore, these animals occupy a key
      position for understanding the evolution of the vertebrate immune system. When
      screening for genes differentially expressed during allorecognition in Botryllus
      schlosseri, we isolated a gene coding for a type II transmembrane protein with a
      C-type lectin-binding domain and close similarity to vertebrates CD94 and NKR-P1.
      Here we show that the gene, BsCD94-1, is differentially regulated during
      allorecognition and that a subpopulation of blood cells carries the corresponding
      receptor on its cell surface. Southern blot analysis with DNA from individual
      colonies and intronless BsCD94-1 probe reveal variation between individuals at
      the genomic level. CD94 in vertebrates is one of the markers for natural killer
      cells and binds to MHC class I molecules. Natural killer cells play a major role
      in recognition and elimination of allogeneic cells. Their evolutionary origin,
      however, remained unknown. The results presented here indicate that the
      elaboration of the vertebrate immune system may have its roots in an ancestral
      population of cells in the urochordate blood.

PMID- 12518048
TI  - Surface gas-exchange processes of snow algae.
AB  - The red-colored chlorophyte Chlamydomonas nivalis is commonly found in summer
      snowfields. We used a modified Li-Cor gas-exchange system to investigate surface
      gas-exchange characteristics of snow colonized by this alga, finding rates of
      CO(2) uptake up to 0.3 micromol.m(-2).s(-1) in dense algal blooms. Experiments
      varying the irradiance resulted in light curves that resembled those of the
      leaves of higher plants. Red light was more effective than white and much more
      effective than green or blue, because of the red astaxanthin that surrounds and
      masks the algal chloroplasts. Integrating daily course measurements of gas
      exchange showed CO(2) uptake around 2,300 micromol.m(-2).day(-1) in heavily
      colonized patches, indicating that summer snowfields can be surprisingly
      productive.

PMID- 12518049
TI  - Optimal ion channel clustering for intracellular calcium signaling.
AB  - Ion channels and receptors in the cell membranes and internal membranes are often
      distributed in discrete clusters. One particularly well-studied example is the
      distribution of inositol 1,4,5-triphosphate receptors in the plasma membrane that
      controls the flux of Ca2+ from the endoplasmic reticulum into the cytosol. By
      using mathematical modeling, we show that channel clustering can enhance the
      cell's Ca2+ signaling capability. Furthermore, we predict optimal signaling
      cellular capability at cluster sizes and distances that agree with experimentally
      found values in Xenopus oocyte.

PMID- 12518050
TI  - High-efficiency recovery of functional hematopoietic progenitor and stem cells
      from human cord blood cryopreserved for 15 years.
AB  - Transplanted cord blood (CB) hematopoietic stem cells (HSC) and progenitor cells
      (HPC) can treat malignant and nonmalignant disorders. Because long-term
      cryopreservation is critical for CB banking and transplantation, we assessed the
      efficiency of recovery of viable HSCHPC from individual CBs stored frozen for 15
      yr. Average recoveries (+/- 1 SD) of defrosted nucleated cells, colony-forming
      unit-granulocyte, -macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and
      colony-forming unit-granulocyte, -erythrocyte, -monocyte, and -megakaryocyte (CFU
      GEMM) were, respectively, 83 +/- 12, 95 +/- 16, 84 +/- 25, and 85 +/- 25 using
      the same culture conditions as for prefreeze samples. Proliferative capacities of
      CFU-GM, BFU-E, and CFU-GEMM were intact as colonies generated respectively
      contained up to 22,500, 182,500, and 292,500 cells. Self-renewal of CFU-GEMM was
      also retained as replating efficiency of single CFU-GEMM colonies into 2 degrees
      dishes was >96% and yielded 2 degrees colonies of CFU-GM, BFU-E, and CFU-GEMM.
      Moreover, CD34(+)CD38(-) cells isolated by FACS after thawing yielded >250-fold
      ex vivo expansion of HPC. To assess HSC capability, defrosts from single
      collections were bead-separated into CD34(+) cells and infused into sublethally
      irradiated nonobese diabetic (NOD)severe combined immunodeficient (SCID) mice.
      CD45(+) human cell engraftment with multilineage phenotypes was detected in mice
      after 11-13 wk; engrafting levels were comparable to that reported with fresh CB.
      Thus, immature human CB cells with high proliferative, replating, ex vivo
      expansion and mouse NODSCID engrafting ability can be stored frozen for >15 yr,
      can be efficiently retrieved, and most likely remain effective for clinical
      transplantation.

PMID- 12518052
TI  - Formation and character of an ancient 19-m ice cover and underlying trapped brine
      in an "ice-sealed" east Antarctic lake.
AB  - Lake Vida, one of the largest lakes in the McMurdo Dry Valleys of Antarctica, was
      previously believed to be shallow (<10 m) and frozen to its bed year-round. New
      ice-core analysis and temperature data show that beneath 19 m of ice is a water
      column composed of a NaCl brine with a salinity seven times that of seawater that
      remains liquid below -10 degrees C. The ice cover thickens at both its base and
      surface, sealing concentrated brine beneath. The ice cover is stabilized by a
      negative feedback between ice growth and the freezing-point depression of the
      brine. The ice cover contains frozen microbial mats throughout that are viable
      after thawing and has a history that extends to at least 2,800 (14)C years B.P.,
      suggesting that the brine has been isolated from the atmosphere for as long. To
      our knowledge, Lake Vida has the thickest subaerial lake ice cover recorded and
      may represent a previously undiscovered end-member lacustrine ecosystem on Earth.

PMID- 12518051
TI  - Genome-based peptide fingerprint scanning.
AB  - We have implemented a method that identifies the genomic origins of sample
      proteins by scanning their peptide-mass fingerprint against the theoretical
      translation and proteolytic digest of an entire genome. Unlike previously
      reported techniques, this method requires no predefined ORF or protein
      annotations. Fixed-size windows along the genome sequence are scored by an
      equation accounting for the number of matching peptides, the number of missed
      enzymatic cleavages in each peptide, the number of in-frame stop codons within a
      window, the adjacency between peptides, and duplicate peptide matches.
      Statistical significance of matching regions is assessed by comparing their
      scores to scores from windows matching randomly generated mass data. Tests with
      samples from Saccharomyces cerevisiae mitochondria and Escherichia coli have
      demonstrated the ability to produce statistically significant identifications,
      agreeing with two commonly used programs, peptident and mascot, in 86% of samples
      analyzed. This genome fingerprint scanning method has the potential to aid in
      genome annotation, identify proteins for which annotation is incorrect or
      missing, and handle cases where sequencing errors have caused framing mistakes in
      the databases. It might also aid in the identification of proteins in which
      recoding events such as frameshifting or stop-codon read-through have occurred,
      elucidating alternative translation mechanisms. The prototype is implemented as a
      clientserver pair, allowing the distribution, among a set of cluster nodes, of a
      single or multiple genomes for concurrent analysis.

PMID- 12518053
TI  - Crystal structure of saposin B reveals a dimeric shell for lipid binding.
AB  - Saposin B is a small, nonenzymatic glycosphingolipid activator protein required
      for the breakdown of cerebroside sulfates (sulfatides) within the lysosome. The
      protein can extract target lipids from membranes, forming soluble protein-lipid
      complexes that are recognized by arylsulfatase A. The crystal structure of human
      saposin B reveals an unusual shell-like dimer consisting of a monolayer of alpha
      helices enclosing a large hydrophobic cavity. Although the secondary structure of
      saposin B is similar to that of the known monomeric members of the saposin-like
      superfamily, the helices are repacked into a different tertiary arrangement to
      form the homodimer. A comparison of the two forms of the saposin B dimer suggests
      that extraction of target lipids from membranes involves a conformational change
      that facilitates access to the inner cavity.

PMID- 12518054
TI  - Addition of the keto functional group to the genetic code of Escherichia coli.
AB  - Although the keto group is the most versatile of the functional groups in organic
      chemistry, it is absent in the genetically encoded amino acids. To overcome this
      natural limitation on protein biosynthesis, we have evolved an orthogonal tRNA
      synthetase pair that makes possible the efficient incorporation of a keto amino
      acid, p-acetyl-l-phenylalanine, into proteins in E. coli with high translational
      fidelity in response to the amber nonsense codon. To demonstrate the utility of
      this keto amino acid, we have used it to modify a protein selectively with a
      small molecule fluorophore and biotin derivative. This additional genetically
      encoded amino acid should greatly expand our ability to manipulate protein
      structure and function both in vitro and in living cells.

PMID- 12518055
TI  - UDP-Glc:glycoprotein glucosyltransferase recognizes structured and solvent
      accessible hydrophobic patches in molten globule-like folding intermediates.
AB  - Protein folding in the cell involves the action of different molecular chaperones
      and folding-facilitating enzymes. In the endoplasmic reticulum (ER), the folding
      status of glycoproteins is stringently controlled by a glucosyltranferase enzyme
      (GT) that creates monoglucosylated structures recognized by ER resident lectins
      (calnexincalreticulin, CNXCRT). GT serves as a folding sensor because it only
      glucosylates misfolded or partly folded glycoproteins. Nevertheless, the
      molecular mechanism behind this recognition process remains largely unknown. In
      this paper we explore the structural determinants for GT recognition by using a
      single domain model protein. For this purpose we used a family of chemically
      glycosylated proteins derived from chymotrypsin inhibitor-2 as GT substrates.
      Structural characterization of species showing higher glucose acceptor capacity
      suggests that GT recognizes solvent accessible hydrophobic patches in molten
      globule-like conformers mimicking intermediate folding stages of nascent
      glycoproteins. It was further confirmed that BiP (binding protein, a chaperone of
      the heat shock protein 70 family) preferentially recognized neoglycoproteins
      displaying extended conformations, thus providing a molecular rationale for the
      sequential BiP-CNXCRT interaction with folding glycoproteins observed in vivo.

PMID- 12518057
TI  - Crystal structure of oxygen-evolving photosystem II from Thermosynechococcus
      vulcanus at 3.7-A resolution.
AB  - Photosystem II (PSII) is a multisubunit membrane protein complex performing light
      induced electron transfer and water-splitting reactions, leading to the formation
      of molecular oxygen. The first crystal structure of PSII from a thermophilic
      cyanobacterium Thermosynechococcus elongatus was reported recently [Zouni, A.,
      Witt, H. T., Kern, J., Fromme, P., Krauss, N., Saenger, W. & Orth, P. (2001)
      Nature 409, 739-743)] at 3.8-A resolution. To analyze the PSII structure in more
      detail, we have obtained the crystal structure of PSII from another thermophilic
      cyanobacterium, Thermosynechococcus vulcanus, at 3.7-A resolution. The present
      structure was built on the basis of the sequences of PSII large subunits D1, D2,
      CP47, and CP43; extrinsic 33- and 12-kDa proteins and cytochrome c550; and
      several low molecular mass subunits, among which the structure of the 12-kDa
      protein was not reported previously. This yielded much information concerning the
      molecular interactions within this large protein complex. We also show the
      arrangement of chlorophylls and cofactors, including two beta-carotenes recently
      identified in a region close to the reaction center, which provided important
      clues to the secondary electron transfer pathways around the reaction center.
      Furthermore, possible ligands for the Mn-cluster were determined. In particular,
      the C terminus of D1 polypeptide was shown to be connected to the Mn cluster
      directly. The structural information obtained here provides important insights
      into the mechanism of PSII reactions.

PMID- 12518056
TI  - Flexibility and molecular recognition in the immune system.
AB  - Photon echo spectroscopy has been used to measure the response of three antibody
      binding sites to perturbation from electronic excitation of a bound antigen,
      fluorescein. The three antibodies show motions that range in time scale from tens
      of femtoseconds to nanoseconds. Relative to the others, one antibody, 4-4-20,
      possesses a rigid binding site that likely results from a short and inflexible
      heavy chain complementarity-determining region 3 (HCDR3) loop and a critical Tyr
      that acts as a "molecular splint," rigidifying the antigen across its most
      flexible internal degree of freedom. The remaining two antibodies, 34F10 and
      40G4, despite being generated against the same antigen, possess binding sites
      that are considerably more flexible. The more flexible combining sites likely
      result from longer HCDR3 loops and a deletion in the light chain complementarity
      determining region 1 (LCDR1) that removes the critical Tyr residue. The binding
      site flexibilities may result in varying mechanisms of antigen recognition
      including lock-and-key, induced-fit, and conformational selection.

PMID- 12518058
TI  - Substructure synthesis method for simulating large molecular complexes.
AB  - This paper reports a computational method for describing the conformational
      flexibility of very large biomolecular complexes using a reduced number of
      degrees of freedom. It is called the substructure synthesis method, and the basic
      concept is to treat the motions of a given structure as a collection of those of
      an assemblage of substructures. The choice of substructures is arbitrary and
      sometimes quite natural, such as domains, subunits, or even large segments of
      biomolecular complexes. To start, a group of low-frequency substructure modes is
      determined, for instance by normal mode analysis, to represent the motions of the
      substructure. Next, a desired number of substructures are joined together by a
      set of constraints to enforce geometric compatibility at the interface of
      adjacent substructures, and the modes for the assembled structure can then be
      synthesized from the substructure modes by applying the Rayleigh-Ritz principle.
      Such a procedure is computationally much more desirable than solving the full
      eigenvalue problem for the whole assembled structure. Furthermore, to show the
      applicability to biomolecular complexes, the method is used to study F-actin, a
      large filamentous molecular complex involved in many cellular functions. The
      results demonstrate that the method is capable of studying the motions of very
      large molecular complexes that are otherwise completely beyond the reach of any
      conventional methods.

PMID- 12518060
TI  - Insufficiently dehydrated hydrogen bonds as determinants of protein interactions.
AB  - The prediction of binding sites and the understanding of interfaces associated
      with protein complexation remains an open problem in molecular biophysics. This
      work shows that a crucial factor in predicting and rationalizing protein-protein
      interfaces can be inferred by assessing the extent of intramolecular desolvation
      of backbone hydrogen bonds in monomeric structures. Our statistical analysis of
      native structures shows that, in the majority of soluble proteins, most backbone
      hydrogen bonds are thoroughly wrapped intramolecularly by nonpolar groups except
      for a few ones. These latter underwrapped hydrogen bonds may be dramatically
      stabilized by removal of water. This fact implies that packing defects are
      "sticky" in a way that decisively contributes to determining the binding sites
      for proteins, as an examination of numerous complexes demonstrates.

PMID- 12518059
TI  - Imaging whole Escherichia coli bacteria by using single-particle x-ray
      diffraction.
AB  - We report the first experimental recording, to our knowledge, of the diffraction
      pattern from intact Escherichia coli bacteria using coherent x-rays with a
      wavelength of 2 A. By using the oversampling phasing method, a real space image
      at a resolution of 30 nm was directly reconstructed from the diffraction pattern.
      An R factor used for characterizing the quality of the reconstruction was in the
      range of 5%, which demonstrated the reliability of the reconstruction process.
      The distribution of proteins inside the bacteria labeled with manganese oxide has
      been identified and this distribution confirmed by fluorescence microscopy
      images. Compared with lens-based microscopy, this diffraction-based imaging
      approach can examine thicker samples, such as whole cultured cells, in three
      dimensions with resolution limited only by radiation damage. Looking forward, the
      successful recording and reconstruction of diffraction patterns from biological
      samples reported here represent an important step toward the potential of imaging
      single biomolecules at near-atomic resolution by combining single-particle
      diffraction with x-ray free electron lasers.

PMID- 12518061
TI  - Asymmetry of the central apparatus defines the location of active microtubule
      sliding in Chlamydomonas flagella.
AB  - Regulation of ciliary and flagellar motility requires spatial control of dynein
      driven microtubule sliding. However, the mechanism for regulating the location
      and symmetry of dynein activity is not understood. One hypothesis is that the
      asymmetrically organized central apparatus, through interactions with the radial
      spokes, transmits a signal to regulate dynein-driven microtubule sliding between
      subsets of doublet microtubules. Based on this model, we hypothesized that the
      orientation of the central apparatus defines positions of active microtubule
      sliding required to control bending in the axoneme. To test this, we induced
      microtubule sliding in axonemes isolated from wild-type and mutant Chlamydomonas
      cells, and then used electron microscopy to determine the orientation of the
      central apparatus. Transverse sections of wild-type axonemes revealed that the C1
      microtubule is predominantly oriented toward the position of active microtubule
      sliding. In contrast, the central apparatus is randomly oriented in axonemes
      isolated from radial spoke deficient mutants. For outer arm dynein mutants, the
      C1 microtubule is oriented toward the position of active microtubule sliding in
      low calcium buffer, but is randomly oriented in high calcium buffer. These
      results provide evidence that the central apparatus defines the position of
      active microtubule sliding, and may regulate the size and shape of axonemal bends
      through interactions with the radial spokes. In addition, our results indicate
      that in high calcium conditions required to generate symmetric waveforms, the
      outer dynein arms are potential targets of the central pair-radial spoke control
      system.

PMID- 12518062
TI  - Nitric oxide-induced cellular stress and p53 activation in chronic inflammation.
AB  - Free radical-induced cellular stress contributes to cancer during chronic
      inflammation. Here, we investigated mechanisms of p53 activation by the free
      radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)
      and ataxia-telangiectasia mutated and Rad3-related-dependent p53
      posttranslational modifications, leading to an increase in p53 transcriptional
      targets and a G(2)M cell cycle checkpoint. Such modifications were also
      identified in cells cocultured with NO-releasing macrophages. In noncancerous
      colon tissues from patients with ulcerative colitis (a cancer-prone chronic
      inflammatory disease), inducible NO synthase protein levels were positively
      correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and
      p21(WAF1) was consistent with transcriptionally active p53. Our study highlights
      a pivotal role of NO in the induction of cellular stress and the activation of a
      p53 response pathway during chronic inflammation.

PMID- 12518063
TI  - Store-operated calcium channel regulates the chemotactic behavior of ascidian
      sperm.
AB  - The sperm-activating and -attracting factor released from the eggs of the
      ascidians Ciona intestinalis and Ciona savignyi requires extracellular Ca(2+) for
      activating sperm motility and eliciting chemotactic behavior of the activated
      sperm toward the egg. Here, we show that modulators of the store-operated Ca(2+)
      channel, SK&F96365, Ni(2+), 2-aminoethoxydiphenylborane, and thapsigargin inhibit
      the chemotactic behavior of the ascidian sperm; on the other hand, blockers of
      voltage-dependent Ca(2+) channels did not inhibit the chemotaxis, even though
      they inhibited the sperm activation operated by voltage-dependent Ca(2+)
      channels. The blockers of store-operated Ca(2+) channels also inhibited the
      asymmetrical flagellar beating and turning movements of the ascidian sperm, which
      are typical signs of sperm chemotaxis. Depletion of internal Ca(2+) stores by
      thapsigargin induced capacitative Ca(2+) entry into the sperm, which was blocked
      by SK&F96365. These results suggest that the intracellular Ca(2+) concentration
      increase through the store-operated Ca(2+) channels induces asymmetrical
      flagellar movements to establish the chemotactic behavior of the sperm.

PMID- 12518064
TI  - Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of
      small interfering RNA against CCR5.
AB  - Double-stranded RNAs approximately 21 nucleotides long [small interfering RNA
      (siRNA)] are recognized as powerful reagents to reduce the expression of specific
      genes. To use them as reagents to protect cells against viral infection,
      effective methods for introducing siRNAs into primary cells are required. Here,
      we describe success in constructing a lentivirus-based vector to introduce siRNAs
      against the HIV-1 coreceptor, CCR5, into human peripheral blood T lymphocytes.
      With high-titer vector stocks, >40% of the peripheral blood T lymphocytes could
      be transduced, and the expression of a potent CCR5-siRNA resulted in up to 10
      fold inhibition of CCR5 expression on the cell surface over a period of 2 weeks
      in the absence of selection. In contrast, the expression of another major HIV-1
      coreceptor, CXCR4, was not affected. Importantly, blocking CCR5 expression by
      siRNAs provided a substantial protection for the lymphocyte populations from CCR5
      tropic HIV-1 virus infection, dropping infected cells by 3- to 7-fold; only a
      minimal effect on infection by a CXCR4-tropic virus was observed. Thus, our
      studies demonstrate the feasibility and potential of lentiviral vector-mediated
      delivery of siRNAs as a general means of intracellular immunization for the
      treatment of HIV-1 and other viral diseases.

PMID- 12518065
TI  - Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells
      and comparative analysis of smallpox vaccines.
AB  - Despite worldwide eradication of naturally occurring variola virus, smallpox
      remains a potential threat to both civilian and military populations. New, safe
      smallpox vaccines are being developed, and there is an urgent need for methods to
      evaluate vaccine efficacy after immunization. Here we report the identification
      of an immunodominant HLA-A*0201-restricted epitope that is recognized by
      cytotoxic CD8(+) T cells and conserved among Orthopoxvirus species including
      variola virus. This finding has permitted analysis and monitoring of epitope
      specific T cell responses after immunization and demonstration of the identified
      T cell specificity in an A*0201-positive human donor. Vaccination of transgenic
      mice allowed us to compare the immunogenicity of several vaccinia viruses
      including highly attenuated, replication-deficient modified vaccinia virus Ankara
      (MVA). MVA vaccines elicited levels of CD8(+) T cell responses that were
      comparable to those induced by the replication-competent vaccinia virus strains.
      Finally, we demonstrate that MVA vaccination is fully protective against a lethal
      respiratory challenge with virulent vaccinia virus strain Western Reserve. Our
      data provide a basis to rationally estimate immunogenicity of safe, second
      generation poxvirus vaccines and suggest that MVA may be a suitable candidate.

PMID- 12518066
TI  - Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small
      interfering RNAs.
AB  - RNA interference is a cellular process of gene silencing in which small duplexes
      of RNA specifically target a homologous sequence for cleavage by cellular
      ribonucleases. The introduction of approximately 22-nt small interfering RNAs
      (siRNAs) into mammalian cells can specifically silence cellular mRNAs without
      induction of the nonspecific IFN responses that are activated by longer RNA
      duplexes. We investigate in this article whether siRNAs can also silence the
      expression of the cytoplasmically replicating hepatitis C virus (HCV) RNAs by
      using a replicon system that supports robust HCV replication, but not the
      production of infectious virions. We report the efficient silencing of both
      cellular lamin AC and HCV RNAs in Huh-7 hepatoma cell lines supporting HCV
      replication. Silencing of HCV RNAs was dose dependent and specific, inasmuch as
      two HCV variants that differ by 3 nt within the target sequence were only
      silenced by the exact homologous sequence for each. siRNAs designed to target HCV
      RNA triggered an exponential decrease in HCV RNA, resulting in an 80-fold
      decrease in HCV RNA after 4 days. The introduction of siRNAs into cells with
      established HCV replication cured >98% of these cells of detectable HCV antigen
      and replication-competent HCV RNAs. These data support the principle of siRNA
      based HCV antiviral therapy.

PMID- 12518067
TI  - Direct interaction with a nuclear protein and regulation of gene silencing by a
      variant of the Ca2+-channel beta 4 subunit.
AB  - The beta subunits of voltage-gated Ca(2+) channels are known to be regulators of
      the channels' gating properties. Here we report a striking additional function of
      a beta subunit. Screening of chicken cochlear and brain cDNA libraries identified
      beta(4c), a short splice variant of the beta(4) subunit. Although beta(4c) occurs
      together with the longer isoforms beta(4a) or beta(4b) in the brain, eye, heart,
      and lung, the cochlea expresses exclusively beta(4c). The association of beta(4c)
      with the Ca(2+)-channel alpha(1) subunit has slight but significant effects on
      the kinetics of channel activation and inactivation. Yeast two-hybrid and
      biochemical assays revealed that beta(4c) interacts directly with the chromo
      shadow domain of chromobox protein 2heterochromatin protein 1gamma
      (CHCB2HP1gamma), a nuclear protein involved in gene silencing and transcriptional
      regulation. Coexpression of this protein specifically recruits beta(4c) to the
      nuclei of mammalian cells. Furthermore, beta(4c) but not beta(4a) dramatically
      attenuates the gene-silencing activity of chromobox protein 2heterochromatin
      protein 1gamma. The beta(4c) subunit is therefore a multifunctional protein that
      not only constitutes a portion of the Ca(2+) channel but also regulates gene
      transcription.

PMID- 12518068
TI  - Estradiol differentially regulates lipocalin-type prostaglandin D synthase
      transcript levels in the rodent brain: Evidence from high-density oligonucleotide
      arrays and in situ hybridization.
AB  - Microarrays comprise an efficient approach to discovering large numbers of
      differentially expressed mRNA transcripts in the CNS resulting from changes in
      hormonal milieu. We used high-density oligonucleotide microarrays to examine the
      short- and long-term actions of estradiol (E(2)) on the transcriptomes from the
      medial basal hypothalamus and other brain regions of E(2)-treated (10 microg)
      adult female mice. Our results have revealed several unanticipated gene
      regulations. Most striking is lipocalin prostaglandin D(2) synthase (L-PGDS),
      which catalyzes the conversion of prostaglandin (PG) H(2) to PGD(2), a
      neuromodulator involved in a variety of functions, including sleep, pain, and
      odor responses. In situ hybridization revealed significant increases in L-PGDS
      expression in the arcuate and ventromedial nucleus of the medial basal
      hypothalamus compared with vehicle controls. The magnitude of these changes is
      approximately 2-fold and suggests a modulatory role for PGD(2) in E(2)-controlled
      neuroendocrine secretions and behaviors. Surprisingly, L-PGDS gene expression is
      reduced 2-fold after E(2) treatment in the ventrolateral preoptic area (VLPO),
      the suspected site of action for the sleep-promoting effects of PGD(2). Finally,
      whereas L-PGDS has been reported to be expressed primarily in oligodendrocytes of
      the adult rodent brain, we demonstrate, immunocytochemically, that L-PGDS is also
      expressed in a population of VLPO neurons. Thus, our data suggest the intriguing
      possibility that E(2) modulation of L-PGDS plays a role in the regulation of
      sleep-wake states through hitherto unknown mechanisms in VLPO neurons and through
      hormone-dependent neuronal-glial cooperation.

PMID- 12518069
TI  - [Comparative efficacy of antalgesics and non-steroidal anti-inflammatory drugs].
AB  - EFFICACY OF ANALGESICS AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: A systematic
      review of randomized clinical trials demonstrates that common analgesics and
      nonsteroidal anti-inflammatory drugs (NSAID) provide short-term pain relief for
      rheumatism-related pain. There have however been few controlled randomized
      studies on the efficacy of analgesics against rheumatism-related pain. On the
      contrary, the numerous trials conducted with NSAID show a wide variety of doses
      for a wide range of products. Finally, trials comparing NSAID with analgesics are
      scarce and heterogeneous. The comparative efficacy of these two types of
      compounds remains difficult to interpret. CHOICE CRITERIA: The criteria used to
      choose an analgesic or a NSAID are not based solely on their efficacy, but also
      on tolerance, patient status and cost. RECOMMENDATIONS: The European League
      Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the
      American Pain Society recommend acetaminophen for first intention treatment, and
      NSAID (e.g. coxibs) for second intention treatment of patient with rheumatism
      related pain.

PMID- 12518070
TI  - [Comparative safety of traditional non-steroidal anti-inflammatory drugs and COX
      2 selective inhibitors].
AB  - SIDE EFFECTS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: Digestive disorders and
      skin and mucosal reactions, more rarely neurosensorial, renovascular, gyneco
      obstetrical and hematological disorders are the main side effects of non
      steroidal anti-inflammatory drugs. DIGESTIVE USEFULNESS OF COXIBS: Coxibs reduce
      the risk of symptomatic complicated or uncomplicated gastroduodenal ulcers by 1
      to 1.5 per 100 patient-years compared with conventional NSAID. They do however
      induce a similar number of dyspeptic disorders and are contraindicated in case of
      inflammatory bowel disease. Extra-digestive tolerance is comparable with that for
      classical NSAID. PLATELET AGGREGATION AND THROMBOSIS: If the patient's vascular
      status requires an anti-platelet agent, aspirin must be combined with the coxib
      which in itself cannot provide cardiovascular protection.

PMID- 12518071
TI  - [Non-drug treatments for osteoarthritis].
AB  - PHYSICAL EXERCISE: Several epidemiological studies and therapeutic trials have
      provided concordant evidence on the beneficial effect of physical exercise in
      degenerative joint disease despite methodological limitations and the higher
      level of proof for knee disease than hip disease. In addition, programs which led
      to beneficial effects were intensive programs, initiated in a hospital setting
      and continued in the patient's home. WEIGHT LOSS: Body weight has a determining
      effect on degenerative bone and joint disease, particularly when the knee is
      involved. It has been demonstrated that the amount of weight loss depends on the
      quality of the physical exercises performed. WALKING AIDS: Different walking
      aids, crutches, special soles and shoes, splints and braces can be proposed for
      patients with degenerative joint disease. These aids constitute an integral part
      of the non-drug therapeutic approach to patient treatment.

PMID- 12518072
TI  - [Efficacy of diacerein on the symptoms and radiographic progression of
      osteoarthritis].
AB  - SYMPTOMATIC EFFECTS OF DIACEREIN: Data obtained from several clinical trials have
      demonstrated that relief of joint pain obtained with the interleukin-1 inhibitor
      diacerein is comparable with that observed with non-steroidal anti-inflammatory
      drugs (NSAIDS) after four to six weeks of treatment and that relief persists
      after treatment withdrawal. Patients taking diacerein are less handicapped, use
      less NSAID and/or analgesics, and have lower demands for care as well as an
      improved quality of life. RADIOGRAPHIC FINDINGS: The ECHODIAH study conducted to
      evaluate the structure-modifying effect of diacerein in hip osteoarthritis.
      TOLERANCE: Drug watch data and clinical trials have confirmed the safety and
      tolerance of diacerein, so there is no limitation on the duration of its use.

PMID- 12518073
TI  - [Comparison of the pharmacologic effect of diacerein and a selective COX-2
      inhibitor in the mouse induced-granuloma model].
AB  - ANIMAL MODEL OF DEGENERATIVE JOIN DISEASE: A mouse model of joint disease with an
      induced granuloma has demonstrated that diacerein inhibits loss of hydroxyproline
      and proteoglycans in joint cartilage, an effect not observed with conventional
      nonsteroidal antiinflammatory drugs (NSAID) or with a specific inhibitor of
      cyclooxygenase-2 (COX-2). Specific COX-2 inhibitors could thus be beneficially
      combined with disease modifying osteoarthritis drugs DMOD such as diacerein.
      ANTIINFLAMMATORY EFFECTS OF COX-2: During the process of inflammation, COX-2
      activity appears to occur at two specific time points, with a peak at 2 hours,
      associated with maximal activity of PGE(2) synthase (proinflammatory
      prostaglandin) and a second peak after 48 hours, associated with increased levels
      of PGD(2) and cyclopentenones (anti-inflammatory prostaglandins). THERAPEUTIC
      IMPLICATIONS: Treatment with NSAID or selective anti-COX-2 agents appears to have
      a beneficial effect during acute phases of inflammation but their use in long
      term regimens appears to have less favorable effects. Use of long-action
      symptomatic treatments without any apparent effect on COX-2, for example
      diacerein, could protect against the potentially deleterious effects of COX-2
      inhibition.

PMID- 12518074
TI  - [Clinical and radiographic status of patients in the ECHODIAH study who underwent
      THA Pertinence of the pain-function index for operative decision making].
AB  - DATA COLLECTION: The ECHODIAH study conducted to evaluate the chondromodulator
      effect of diacerein on the osteoarthritic hip joint has provided epidemiological
      data on patient symptoms at three-month intervals. Patients with degenerative hip
      joints evaluated their pain and handicap on visual analog scales. The Lequesne
      functional score was also determined. A radiographic study was performed every
      year. IMPROVED PREDICTIVE FACTORS: Among the 507 patients included in the study,
      135 underwent total hip arthroplasty. Clinical and radiological evaluations of
      the operated patients demonstrated that the Lequesne functional score was the
      best predictive factor with an optimal cutoff at 12 points. The second best
      predictive factor was the radiographic measurement of the joint space.

PMID- 12518075
TI  - [Diagnostic approach to the rheumatoid wrist from plain radiographs].
AB  - OBJECTIVE: Monitor a reproducible analysis method based on a simple algorithm.
      DIAGNOSIS OF RHEUMATOLOGIC DISEASE IN WRISTS: The first step is to examine the
      joint space. When the space is preserved, diagnosis may be established on the
      presence of bony defects, demineralization or erosions. DIAGNOSIS OF
      RHEUMATOLOGIC DISEASE IN FINGERS: The first step is to determine whether the
      patient has degenerative or inflammatory joint disease involving the joint space
      or bone disease where bony lesions predominate.

PMID- 12518076
TI  - [How to make a radiographic evaluation of the degenerative knee?].
AB  - EVALUATION AND PROGRESSION OF JOINT DEGENERATION: Progressive destruction of the
      joint cartilage, seen as joint space narrowing on standard x-rays, is one of the
      key features indicative of the severity of joint degeneration. Quantitative
      measurements of space narrowing in the knee joint provide complementary
      information. Analysis techniques using fluoroscopic and standard views have been
      developed. REPRODUCIBILITY: The coefficients of variation of the different
      techniques used to measure joint space demonstrate their relative reliability.
      When studying disease progression over time, for example during longitudinal
      studies, coefficients of variation have however been very wide. X-RAY QUALITY:
      The pertinence of the radiographic exploration requires obtaining high quality X
      rays of the knees, a rather difficult task.

PMID- 12518077
TI  - [Causes of death in HIV-infected French drug users, 1995-2000].
AB  - Since the decline in mortality among HIV-infected persons after introduction of
      highly active antiretroviral therapy, concerns related to co-morbidities have
      increased as they may impair vital prognosis, particularly in intravenous (IV)
      drug users. We describe firstly the changes in the distribution of the causes of
      death between 1995 and 2000 among IV drug users in the "Aquitaine Cohort" based
      on hospital information system, and secondly the distribution of the causes of
      death among IV drug users in the French national survey "Mortalite 2000"
      specifically set up in 2000 for optimal exhaustiveness. The total number of
      deaths declined between 1995 and 2000 and 1/3 were IV drug users. Deceased IV
      drug users were younger than other deceased patients, had longer median time from
      diagnosis of HIV infection and higher median CD4 cell count. Poor socio-economic
      conditions were notified in 55%. Among IV drug users, the proportion of AIDS
      related deaths was above 75% in 1995 and below 30% in 2000. In 2000, 25% of
      deaths were HCV-related, 12% of deaths were due to accident, overdose or suicide,
      and 8% were due to non-AIDS non-HCV related cancer. Among IV drug users,
      improvement in vital prognosis requires to improve management of HCV infection
      and to take into account socio-economic conditions and other addictive behaviours
      like alcohol consumption and smoking.

PMID- 12518078
TI  - Methadone treatment in Ontario after the 1996 regulation reforms. Results of a
      physician survey.
AB  - Over two decades of rather restrictive regulations have kept the availability of
      methadone treatment (MT) at low levels in the province of Ontario, Canada.
      Regulatory changes in the Province of Ontario in the mid-1990s relaxed relevant
      authorization and treatment practice guidelines. Subsequently, the number of
      physicians authorized for methadone treatment and treatment spots increased
      substantially. A large number of the newly authorized physicians are
      general/local medical practitioners. This study reports on the results of a
      survey conducted with the majority of MT prescribing physicians in Ontario
      authorized at the time of study. Physicians were surveyed on their attitudes and
      practices with regards to the MT authorization system, treatment approaches,
      requirements and workload, patient 'stability', additional opiate substitution
      treatment needs, and with regards to general issues and concerns about the new MT
      governance system. The article also discusses patterns and differences that were
      found between physicians when comparing their geographic location, whether they
      see themselves practicing under a 'harm reduction' or an 'abstinence' approach,
      and whether they received MT authorization under the old or the new guidelines.
      It is concluded that the liberalized regulations and the increased incorporation
      of local physicians seems to provide for an overall more desirable system of
      governance of MT. However, some relevant concerns about the current system exist
      and are discussed.

PMID- 12518079
TI  - [Treatment of affective disorder in hepatitis C. A prospective study in 50
      patients].
AB  - Hepatitis C represents a major public health challenge due to its chronic course
      and major complications (e.g. liver tumor and cirrhosis). New treatment
      strategies (pegylated interferon +/- ribavirin) have recently improved the
      prognosis except in case of poor compliance. Psychiatric comorbidity, especially
      affective disorders, is commonly associated with hepatitis C and constitutes the
      main cause of poor compliance and treatment contraindication. The primary aim of
      our study was to emphasize the utility of a multi-disciplinary approach including
      psychiatric evaluation and preventive follow-up. The secondary objective was to
      show that a previous history of depression or attempted suicide should not be
      considered as a formal contraindication prohibiting the implementation of a
      specific follow-up. Fifty interferon treated patients were included in a
      prospective study: 20 were seen in an emergency setting in a context of anxiety
      or major depressive disorders after the initiation of the interferon treatment
      and 30 were followed on a systematic basis prior to the initiation of the
      interferon treatment. Our data confirm the high rate (52%) of major depressive
      disorders among the population of hepatitis C treated patients. A previous
      history of alcoholism might be predictive of such a complication. According to
      the subjective feeling of patients with previous break'off treatment associated
      with major depressive disorders, specific psychiatric follow-up may improve
      tolerance for the treatment. In conclusion, a previous history of depressive
      disorder or attempted suicide should not be considered as a contraindication, but
      should imply a specific psychiatric follow-up especially when alcoholism and
      previous break'off treatment are reported.

PMID- 12518080
TI  - [Is buprenorphine a potential alternative to methadone for treating pregnant drug
      users? Inventory of clinical data in the literature].
AB  - In this review of the literature, we collected 102 case reports of newborns
      exposed in utero to buprenorphine between 1996 and 2000. Reported data show that
      infants born to a mother taking buprenorphine are delivered at term and have a
      birth weight close to infants not exposed to these substances. The published data
      also showed that observations have varied concerning the frequency, intensity,
      and duration of the withdrawal syndrome in newborns exposed in utero to
      buprenorphine.

PMID- 12518081
TI  - [Bupropion: risks and advantages of its use. What preclinical research says].
AB  - There is evidence that nicotine, the major constituent of cigarette smoking,
      leads to addiction. Although a high percent of smokers express the desire to
      quit, only a small percentage of them are successful in achieving sustained
      abstinence. Until recently, pharmacological options for treatment of tobacco
      dependence were primarily limited to the various nicotine replacement therapies.
      Bupropion provides clinicians and patients with a new non-nicotine alternative.
      The mechanisms by which bupropion acts as an aid in smoking cessation are
      unknown. This article is a review of the few explanations taken from the
      literature, to answer questions about the potential risks of the use of this
      atypical antidepressant.

PMID- 12518082
TI  - [Fatal strychnine intoxication. A case report].

PMID- 12518083
TI  - [Informing the hepatitis C diagnosis and the liver biopsy decision. A painful
      case].

PMID- 12518084
TI  - [Analysis of the active consultation files in a specialized drug user care center
      in the North of France. Preliminary results].

PMID- 12518085
TI  - Bulgaria: the urgent need for the development of maintenance treatments.

PMID- 12518086
TI  - [Anhedonia and emotional awareness: facts and perspectives in eating disorders].
AB  - According to clinical reports, patients with eating disorders (EDs) are unable to
      differentiate and regulate emotional states. They are hypothesized alexithymic
      and lacking of emotional awareness. We investigate EDs capacity to experiment
      pleasure and levels of emotional awareness, in a comparative study. As expected,
      EDs show a global deficit of emotional functioning, with inability to identify
      and describe their own emotions, as well as an impairment in mentalising others'
      emotional experience, and an anhedonia. No relations between the duration of
      illness and the emotional dimensions were found. This trouble in regulation of
      emotions either follows the eating disorder and constitutes a lasting sequel, or
      appears to be a personality trait

PMID- 12518087
TI  - [Brain imaging and eating disorders].
AB  - Among the brain imaging studies that have been conducted in eating disorder
      patients, some focused on the morphological alterations associated with these
      disorders, and others aimed at investigating functional cerebral alterations of
      these patients. However, very few studied the links between the observed
      morphological and functional alterations and cognitive functioning of these
      patients more specifically. Here we report the results provided by the various
      brain neuroimaging techniques that were used to assess brain structure and
      functioning, and neuroendocrine dysregulation of eating disorders patients. A
      number of abnormalities evidenced by neuroimaging studies, notably the structural
      ones, do not seem completely reversible with clinical improvement. This article
      stresses the need for more imaging studies examining to which extent these
      alterations are reversible. Based on animal and human literature describing the
      neural bases of eating behavior, that highlight potential pathophysiological
      mechanisms that may be involved in the etiology of eating disorders, we will try
      to determine how understanding eating disorders pathophysiology could benefit
      from the use of neuroimaging.

PMID- 12518091
TI  - [Information of Japanese Society of Radiation Safety Management (JRSM)].

PMID- 12518092
TI  - [Report on the European cancer conference].

PMID- 12518095
TI  - [Reflection on editorial board for advice of honorary counsel Kunio Doi].

PMID- 12518097
TI  - [Dosimetric verification in intensity modulated radiation therapy].
AB  - As part of dosimetric verification for IMRT intensity modulated radiation
      therapy, we examined the selection of a dosimeter in accordance with the purpose
      of physical measurement and the process of data analysis. Because of the high
      dose conformation in the target volume and minimum dose in the organs at risk
      (OAR) in IMRT, dosimetric verification is essential. Because the performance of
      dosimetric verification in a patient is not allowed, a physical phantom and
      dosimeter must be used. Dose verification using a physical phantom, from which
      the beam data optimized for a patient slated for IMRT are transferred, may cause
      latent error as a result of change in the depth of each beam toward an isocenter.
      This effect may change the dose distribution and prescription dose. The basic
      methods of dosimetric verification with physical measurement are point dosimetry,
      when the reference dose is given at a point by planning software, and volumetric
      dosimetry, when planning software gives the dose as a volumetric configuration.
      While the most accurate dosimetry is done using a calibrated ionization chamber,
      IMRT requires volumetric dosimetry using some kind of portal film or a polymer
      gel dosimeter, because of the need for dosimetric verification for an irregular
      dose distribution in IMRT. The importance of indirect dosimetry using these
      methods is to provide calibration as a dosimeter, absolute dose, and preservation
      of calibration. In our study, the verification of dose distribution for IMRT
      using portal film and a RANDO phantom could be performed with an error of less
      than 2% in all cases. The measurement error for the central dose using a JARP
      type ionization chamber and MixDP was less than 3% in all cases except for the
      case with the maximum error. At the moment, IMRT requires a great deal of effort
      in the processes of planning, dosimetric verification, and isocenter checking in
      every fraction to maintain high accuracy. Although the need for a large amount of
      effort in the service of maintaining accuracy may be reasonable, it could be
      enough to inhibit the spread of IMRT. It is hoped that an easy method of
      dosimetric verification that still maintains a high level of accuracy will
      develop as a result of this great effort.

PMID- 12518099
TI  - [Examination of dose verification in intensity modulated radiation therapy (IMRT)
      treatment planning using averaging dose in chamber volume].
AB  - Since the year 2000, our hospital has been equipped with an intensity modulated
      radiation therapy (IMRT) facility. Before IMRT is administered, the absorbed dose
      is measured by the ionization chamber to provide verification for the IMRT
      procedure. In utilizing the current point dose evaluation, large discrepancies
      have been experienced when the measured dose is compared with the calculated
      dose. This discrepancy is due to the lack of uniformity in IMRT irradiation in
      comparison with that of the present method of dose distribution. In order to
      reduce the margin of error, the average dose of the ionization chamber calculated
      on a dose-volume histogram was compared with the measured dose. As a result, the
      margin of error was minimized to <2% in uniform areas and <4% in non-uniform
      areas.

PMID- 12518098
TI  - [Accuracy of dynamic multileaf position and influence of beam profile according
      to change in dose monitor unit in QA plan of intensity modulated radiotherapy].
AB  - The number of dose monitor units in IMRT QA plans differs form the actual
      conditions of IMRT in dosimetry for verification of dynamic multileaf-IMRT (DMLC
      IMRT). We measured the accuracy of the position of the dynamic multileaf
      collimator and the dose profile for various numbers of dose monitor units, and
      verified the accuracy of dosimetry in an IMRT QA plan. The accuracy of the
      position of the dynamic multileaf collimator was measured by using the software
      of the external irradiation device, and the dose profile was measured by using
      the semiconductor profiler. Deviation in the position of the dynamic multileaf
      collimator increased as the number of dose monitor units decreased. When
      deviation in the position of the dynamic multileaf collimator was large and the
      gap width of the multileaf collimator was narrow, the change in dose profile was
      large. Therefore, verification of IMRT QA plans requires a phantom and
      measurement device close to the actual conditions of IMRT.

PMID- 12518100
TI  - [Output factor calculations for intensity modulation radiation therapy as
      dosimetry quality assurance].
AB  - Because intensity-modulated radiation therapy (IMRT) is complicated by many
      small, irregular, and off-center fields, dosimetry quality assurance (QA) is
      extremely important. QA is performed with verifications of both dose
      distributions and some arbitrary point doses. In most institutes, verifications
      are carried out in comparison with dose values generated from radiation treatment
      planning systems (RTPs) and actually measured doses. However, the estimation of
      arbitrary point doses without RTPs should be feasible in order to perform IMRT
      delivery more safely and accurately in terms of the clinical aspect. In this
      paper, we propose a new algorithm for calculating output factors at the center
      point of the collimations in an IMRT field with step and shoot delivery machines
      in which the lower jaws were replaced with multileaf collimators (MLC). We
      assumed that output is independently affected by collimator scatter and total
      scatter according to the position of the upper jaws and each of the MLC leaves
      (lower jaws). Then, the two scatter factors are accurately measured when changing
      their position. Thus, the output factor for an irregular field could be
      calculated with the new algorithm. We adopted this technique for some irregular
      fields and actual IMRT fields for head-and-neck cancer and found that the
      differences between calculated and measured output values were both small and
      acceptable. This study suggests that our methods and this algorithm are useful
      for dosimetry quality assurance.

PMID- 12518101
TI  - [New method of verification of the position of target points in stereotactic
      radiosurgery by linear accelerator].
AB  - A method for quantitatively checking the position to be used for stereotactic
      radiosurgery was devised using a digital reconstruction radiogram (DRR) and
      electric portal images (EPI). On each image, the radiation field and head contour
      were extracted by binary-coded processing. The center of gravity position vector
      of the extracted image was calculated, and the vector from the head contour to
      the radiation field was obtained. By comparing the difference in DRR and EPI, an
      index was made of positional error. The error in the center of gravity position
      coordinate in changing 40~80 of 256 image tones in the binary operation was 0.5mm
      or less. The effect on the center of gravity position vector caused by the image
      distortion of EPI was within 0.5mm in the 200x200mm(2) region. Statistical
      processing was carried out on this index value, and a 95% confidence interval was
      estimated. The index value of the Z component of the lateral image became -1.43+/
      0.66, and it shifted to the negative side. Error was evaluated by the
      verification method devised for the target point position. Results indicate the
      usefulness of the verification method using center of gravity for the target
      point position.

PMID- 12518102
TI  - [Depth dose characteristics of photon beams released from a scanning-type
      racetrack microtron].
AB  - The MM50 is a racetrack microtron that can emit photon beams or electron beams up
      to 50 MeV. The MM22 using the scanning beam method and the MM22 using a
      flattening filter method both to flatten the emission field and a water phantom
      with particular function measurable of PDD etc. in an accelerator using the
      scanning beam method to make up the PDD curve of photon beams from the linear
      accelerator. The Clinac21EX was thus employed. The maximum depth of beam flux was
      shallow, the gradient of the flux decrement large, the surface dose large, and
      the estimated nominal energy low to the same nominal energy. From these findings,
      it can be said that thorough comprehension of the characteristics of beam flux
      properties for these units is necessary when photon beams are to be used.

PMID- 12518103
TI  - [Dose outside the treatment field for external irradiation with high-energy X-ray
      reduction of the dose of the remaining testis in postoperative irradiation of
      seminoma].
AB  - This study aimed to decrease the radiation dose to the disease-free testis in
      postoperative irradiation for seminoma patients. We consider the factors
      influencing the peripheral dose (PD) of 10MV X-ray radiotherapy to be the
      distance between the caudal edge of the irradiation field and the measuring
      point, the size of the therapeutic irradiation field, the thickness of the lead
      shield laid above and lateral to the disease-free testis, and the thickness of
      the lateral absorber. MATERIALS AND METHODS: We measured the scattering radiation
      dose coming from the accelerator head and that due to irradiation volume. We
      measured these doses using a testicular phantom as the non-diseased testis.
      RESULTS: Scattering radiation from the accelerator head mainly contributes to PD,
      whereas the larger the size of the irradiation field the more the scattering
      radiation from the irradiation volume contributed to PD. PD changed more at the
      surface of the phantom than at its center. PD at the testicular phantom could be
      reduced to less than 1% of the therapeutic dose when it was situated more than
      5cm distant from the caudal limit of the irradiation field, the lead shield above
      the testicular phantom was 7.5cm thick, and the lateral lead shield was 2mm
      thick. CONCLUSIONS: PD is influenced by many factors. It is necessary to clarify
      the change in PD at the testicular phantom, and it is important to limit the
      caudal edge of the irradiation field and to lay the lead shield for the
      attenuation of radiation on the disease-free testis.

PMID- 12518104
TI  - [Measurement of the mean energy of the off-axis incident electron without the
      beam guide: using a scintillating fiber beam-energy monitor for electron beam
      therapy].
AB  - In the case of total skin electron therapy without the beam guide, the electron
      beam is scattered just outside the gantry exit, dose uniformity in the field is
      broken, and dose is spread outside the light field. The aims of this study were
      to measure the mean energy of the off-axis incident electron beam without the
      beam guide and to establish a reference for the clinical situation. For the
      measurement, a 4 MeV electron beam was selected among several energies from the
      linear accelerator. A scintillating fiber beam energy monitor measured the mean
      energy of the incident electron beam. This energy monitor is a small, light
      weight piece of equipment composed of a wedge absorber, scintillation fiber, and
      photodiode. We found the relationship between electron energy and the indicated
      value of the energy monitor by means of the estimation of correction factors for
      five different kinds of electron energy. The preferable linear correlation of
      0.997 of the coefficient of determination (R(2)) was obtained. From the results
      of measurement at each point, those variations due to the off-axial distance were
      about 5% within the measured area. It was assumed that the energy did not change
      rapidly beyond the light field. Clinically, this amount of variation in energy
      may not cause any problem.

PMID- 12518105
TI  - [Usefulness of a dose distribution analysis system with a common scanner].
AB  - Although one-dimensional densitometry has been widely performed for linac
      dosimetry, it is a time-consuming, labor-intensive procedure. We studied a new
      densitometry system (DD-System) that consists of a personal computer and common
      flatbed-type scanner, with regard to its usefulness for daily QC checks in
      comparison with conventional densitometry. The spatial resolution of the DD
      System is very high, and its accuracy of measurements of field size and flatness
      are equivalent to those of a conventional system at an optical density <2.0.
      Although the performance of the image scanner limits the maximum optical density
      of our system, this system can acquire high-resolution two-dimensional dose
      distributions quickly and easily. In conclusion, the DD-System is very useful for
      reducing the amount of time and effort required in daily QC activities. We
      consider this system applicable to the analysis of complicated dose distributions
      in this era of IMRT.

PMID- 12518106
TI  - [Improvement of dose distribution of esophageal irradiation using the field
      within-a-field technique].
AB  - The wide radiation field for mediastinal dose distribution should be
      inhomogeneous with the usual simple opposed beam irradiation. The purpose of this
      study was to improve the dose distribution of the mediastinum using a
      conventional planning system with a dose-volume histogram (DVH) and the field-in
      field technique. Three-dimensional (3D) dose distribution is obtained in
      bilateral opposed-field irradiation. An overdose area obtained from the 3D dose
      distribution is defined and reprojected into the irradiation field. A new reduced
      field is created by removing the reprojected overdose area. A 3D dose
      distribution is again obtained and compared with the results from first one.
      Procedures were repeated until each of the target volumes was within +/-5% of the
      prescribed dose and the irradiation volume within 107% or less of the prescribed
      dose. From the DVH analysis, our field-within-a-field technique resulted in a
      more uniform dose distribution within the conventional planning. The field-within
      a-field technique involves many parameters, and an inverse planning algorithm is
      suitable for computation. However, with our method, the forward planning system
      is adequate for planning, at least in a relatively straightforward planning
      system such as bilateral opposed fields therapy.

PMID- 12518107
TI  - [Comments on evaluation method for equivalent square fields to the collimator
      scatter factors of rectangular fields].
AB  - In the measurement of 4 MV and 10 MV X-ray collimator scatter factors (S(c)), the
      method of using an acrylic mini-phantom showed no significant differences between
      cases in which the chamber axis was either parallel or perpendicular to the beam
      axis. Chamber readings with an aluminum or acrylic build-up cap were not
      reflected by contaminant electrons when the chamber axis was parallel to the beam
      axis. On the basis of the data on 4 MV and 10 MV X-ray collimator Sc measured
      using an acrylic mini-phantom, we examined three methods of obtaining square
      fields equivalent to rectangular fields, and reached the following conclusions:
      (1) The A/P method was not accurate because it did not take into account the
      structure of the radiation head. (2) Regarding the geometrical weight factor (k)
      used in the field-mapping method, more accurate k values were obtained when using
      the geometrical places of the flattening filter (or the second source, taken from
      the concept of extra-focal radiation), the upper and lower collimators, and the
      chamber, rather than when using the geometrical places of the source, the upper
      and lower collimators, and the chamber. (3) The most accurate k values could, in
      general, be obtained when determined on the basis of measured S(c) data.

PMID- 12518108
TI  - Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the
      treatment of chronic venous insufficiency. A meta-analysis of randomized
      controlled trials and large observational studies.
AB  - BACKGROUND: Safe and effective oral therapies for chronic venous insufficiency
      (CVI) would provide an important alternative to mechanical compression treatment.
      Several narrative reviews and one systematic review have summarized the efficacy
      of horse chestnut seed extract (HCSE), but to our knowledge no systematic review
      has included data from both randomized controlled trials (RCTs) and large-scale
      observational studies regarding outcomes as well as adverse events. METHODS:
      Using a systematic literature search, we identified 13 RCTs of CVI (1,051
      patients) and 3 observational studies (10,725 patients) that met our inclusion
      criteria. Examined outcomes were leg volume, ankle and calf circumference, edema,
      pain, sensation of tension, swelling, leg fatigue/heaviness, calf cramps, and
      itching. Random and fixed effect models were used to pool outcomes and adverse
      events separately for RCTs and observational studies. RESULTS: Overall, the RCTs
      indicated that HCSE improved symptoms in patients with CVI. Compared to placebo,
      HCSE reduced leg volume by 46.4 ml (95% CI, 11.3-81.4 ml) and increased the
      likelihood of improvement in leg pain 4.1-fold (95% CI, 0.98-16.8). Similarly,
      improvement probabilities were increased 1.5-fold (95% CI, 1.2-1.9) for edema and
      1.7-fold (95% CI, 0.01-3.0) for itching. There was insufficient evidence to
      demonstrate HCSE's effect on leg fatigue/heaviness or calf cramps. Observational
      studies showed significant effectiveness regarding pain, edema, and leg
      fatigue/heaviness. No severe adverse events were reported, and HCSE did not
      significantly increase mild adverse events. CONCLUSIONS: Based on meta-analyses
      of RCTs and observational studies, HCSE appears to be an effective and safe
      treatment for CVI. Further RCTs and carefully conducted large-scale observational
      studies are required to evaluate the long-term effectiveness and safety of HCSE
      in routine settings.

PMID- 12518109
TI  - The incidence of venous disease in Brazil based on the CEAP classification.
AB  - BACKGROUND: Venous disease presents an extremely complex problem with various
      clinical manifestations. This is an epidemiological study of venous disease as it
      occurs in an area of Brazil. For the first time in Brazil the CEAP classification
      is used. METHODS: A total of 2104 people, were randomly recruited at the
      registration desks of the General Policlinic Department of the University
      Hospital and public health centers. The "C" of the CEAP classification was used
      to classify the clinical features of the venous diseases. The subjects were
      categorized according to sex and age. In addition, women were also subdivided
      according to number of their pregnancies. RESULTS: In the age group of females
      aged 14 to 22, we found 46.42% without symptoms and obvious veins (CEAP 0A/0A).
      Only 12.29% were symptomatic, and 41.25% of all patients in this group presented
      with visible veins or telangiectasias, though without symptoms. In the age group
      of women ranging from 23 to 48, 66.47% had had up to 3 pregnancies. In this group
      10.43% were (CEAP 0A/0A). Those who had symptoms with prominent veins totaled
      37.53% and those who presented with prominent veins without symptoms, 51.83%. In
      the female group over 48 years of age, only 4.67% were (CEAP 0A/0A). The majority
      (62.79%) had symptoms and prominent veins. In the male group, the greater part
      (65.54%) was (CEAP 0A/0A). Only 13.97% were considered symptomatic with some kind
      of prominent veins. CONCLUSIONS: This large epidemiological study is the first in
      Brazil to validate the CEAP classification as an important tool in the
      epidemiology of venous pathology: a method allowing an objective approach to
      venous disease. The data in this study were similar to those of western
      countries. Venous disease was found to be much more frequent in females than
      males. Age and number of pregnancies are important factors in the development of
      the disease. Over 50% of young women presented with visible veins in their legs
      but were without symptoms and this was considered a purely esthetic problem.

PMID- 12518110
TI  - Spectrum and prevalence of prothrombotic single nucleotide polymorphism profiles
      in the Greek Cypriot population.
AB  - BACKGROUND: This study was performed to establish the allele, genotype and
      genotype combination/SNP (single nucleotide polymorphism) profile frequencies in
      the general population of Cyprus for 6 genes implicated in thrombotic disorders.
      The genes with their respective functional polymorphisms were the following:
      factor V (G1691A), prothrombin/factor II (G20210A), methylenetetrahydrofolate
      reductase (C677T), platelet glycoprotein receptor IIIa (P1A1/A2), b-fibrinogen
      (G/A-455) and plasminogen activator inhibitor-type 1 (4G/5G). METHODS: DNA
      samples from 121 unrelated individuals were used for this epidemiological study.
      The polymerase chain reaction followed by restriction digestion were used to
      genotype the 6 different polymorphic loci. Allele and genotype frequencies were
      established and shown to be in Hardy-Weinberg equilibrium. RESULTS: Mutant allele
      frequencies for the 6 genes were as follows: factor V-4%, prothrombin-2%,
      methylenetetrahydrofolate reductase -39%, platelet glycoprotein receptor IIIa
      16%, beta-fibrinogen-17% and plasminogen activator inhibitor - type 1-46%.
      Combined defects occurred which may increase the risk for vascular events, 33% of
      individuals (39/118) had 3 or more of the above mutations. CONCLUSIONS: As in
      other European populations, prospective case-control studies to estimate the risk
      for deep vein thrombosis (DVT) and ischemic episodes with respect to genetic and
      environmental risk factors should be performed. Thrombophilia screening should be
      applied for primary and secondary prevention of thrombotic episodes in
      susceptible individuals on the island of Cyprus. Individuals targeted for such
      screening include those with the following: a positive family history for
      thrombosis; a previous DVT or other ischemic episode; prior exposure to
      circumstantial risk factors and in the presence of echolucent plaques.

PMID- 12518111
TI  - Venous thromboembolism. Prophylaxis on a Saturday morning in a district hospital.
AB  - BACKGROUND: Implementation of guidelines to prevent venous thromboembolism (VTE)
      is essential to help guide junior medical staff but adherence to such protocols
      is insufficient. This study aims to audit the use of VTE prophylaxis (Tinzaparin
      3500 units and/or thromboembolic deterrent stockings (TED) in general surgical
      inpatients in a district hospital on a random day at the beginning (Group A) and
      at the end of the junior house officer's 6 monthly term (Group B). METHODS:
      Patients were analyzed within the subgroups elective and emergency admissions and
      assessed regarding the appropriate prescription of tinzaparin and TED-stockings.
      The presence of a significant time lag between patients arriving on the ward and
      VTE-prophylaxis being prescribed was documented. RESULTS: Tinzaparin was
      appropriately prescribed or not prescribed if contraindicated in 86% of elective
      admissions in Group A (versus 91% in Group B) and in 58% of emergency admissions
      in Group A (versus 85% in Group B). The subcutaneous injection of tinzaparin was
      commenced on the day of admission in 67% in Group A and in 75% of patients in
      Group B. CONCLUSIONS. Despite the institution of local guidelines adherence to
      such recommendations appears to be sub-optimal even at the end of the junior
      house officer's 6 monthly term when one would expect a higher vigilance.

PMID- 12518112
TI  - Duplex imaging analysis of the long saphenous vein reflux: basis for strategy of
      endovenous obliteration treatment.
AB  - BACKGROUND: The purpose of this study was to characterize greater saphenous vein
      (GSV) reflux in order to better define indications for appropriate endovascular
      obliteration treatment. METHODS: Color-flow duplex imaging was used prospectively
      to categorize 133 lower limbs of 102 consecutive outpatients, presenting with
      chronic superficial vein disease associated with GSV incompetence. Sapheno
      femoral junction (SFJ) and tributaries morphology and hemodynamics, and GSV main
      trunk reflux extent were assessed. RESULTS: GSV reflux was related to terminal
      valve incompetence in 70 (52.3%) limbs, to sub-terminal valve incompetence in 37
      (27.8%), and to segmental incompetence of the GSV trunk in 26 (19.6%). Reflux
      originated from common femoral vein (CFV) and/or SFJ tributaries and/or GSV
      collaterals, including multiple origins combinations. CFV was the reflux origin
      in 77 (57.9%). GSV reflux arose from SFJ or trunk tributaries in 69 (51.9%) and
      32 (24%), limbs respectively. Circumflex and superficial epigastric veins were
      involved in 65.2% and 50.7% respectively of the SFJ tributaries. GSV reflux
      extended down to the mid-third of the calf or below in only 45 cases (33.7%). The
      age of the patients was not correlated with reflux origin. CONCLUSIONS:
      Preliminary analysis suggests that in 2/3 of the cases, endovenous obliteration
      treatment should extent from the thigh to just below the knee. Furthermore, in
      order to preserve GSV competent valves and collateral veins drainage, treatment
      should start just below the main SFJ tributary when the terminal valve is still
      competent, and just below the main branches connection when only the GSV trunk is
      incompetent.

PMID- 12518113
TI  - Changes of elastic and collagen fibers in varicose veins.
AB  - BACKGROUND: The resistance to stretch and the elasticity of the vein wall depend
      on the collagen and elastic fibers, respectively. Contradicting evidence exists,
      however, on the connective tissue concentration in varicose veins. METHODS: A
      prospective, comparative study was conducted at Asir Central Hospital and the
      College of Medicine in Abha, Saudi Arabia. Twenty-three vein specimens collected
      from both the proximal thigh long saphenous vein (LSV) and the distal calf
      blowouts in 10 primary varicose vein patients and from the normal, proximal thigh
      LSV in 3 young vascular trauma patients were examined. Paraffin sections stained
      with hematoxylin and eosin, Verhoeff von Gieson (VVG) and Masson's Trichrome
      stains were examined under the light microscope. Ultra thin sections were
      examined under the transmission electron microscope (TEM). RESULTS: Compared with
      the normal control LSV, varicose vein sections showed increased diameter of the
      lumen and hypertrophy of the wall, mainly of the intima, due to increased amounts
      of collagen fibers. This marked fibrous infiltration disrupted the normal
      palisade arrangement of the intimal and the regular sheet-like arrangement of the
      medial smooth muscle cells. Collagen fibers also lost their normal pattern and
      showed abnormal forms. Elastic fibers lost their regular laminar arrangement and
      formed clumps or scattered fragments. CONCLUSIONS: Varicose veins showed
      increased collagenosis and distortion of the elastic fibers. The presence of
      abnormal collagen to elastin ratio and the loss of the regular collagen/elastic
      lattice of the vein wall may play a major role in the pathogenesis of varicose
      veins.

PMID- 12518114
TI  - Microembolization during carotid stenting with the distal-balloon antiemboli
      system.
AB  - BACKGROUND: The distal-balloon protection system is being evaluated for its
      efficacy in preventing embolic neurological events during carotid stenting (CAS).
      We sought to determine the effect of this system on the frequency of the Doppler
      detected microembolic signals (MES) during CAS. METHODS: Using transcranial
      Doppler, we compared the frequency of MES during CAS in 2 groups; 39 patients
      without distal protection and 37 with the distal-balloon protection system
      (GuardWire, Percusurge, Sunnyville, CA). There was no significant difference in
      the clinical or angiographic characteristics between the 2 groups. Three phases
      with increased MES counts were identified during the unprotected CAS; stent
      deployment, predilation, and postdilation (mean+/-SD: 75+/-57, 32+/-36, and 27+/
      25, respectively). RESULTS: The distal-balloon protection significantly reduced
      the frequency of MES during CAS (MES-counts: 164+/-108 in the control vs 68+/-83
      in the protection group, p=0.002) particularly during these 3 phases. MES in the
      protection group were detected predominantly during sheath placement, guidewire
      manipulation and during the distal-balloon deflation. CONCLUSIONS: Three phases
      with increased MES counts were identified during the unprotected CAS, e.g. stent
      deployment, predilation and postdilation. The distal-balloon protection system
      significantly reduced the frequency of MES during CAS, particularly during these
      3 phases.

PMID- 12518115
TI  - Aortoiliac angulation and the need for secondary procedures to secure stent graft
      fixation: which angle is important?
AB  - BACKGROUND: The purpose of this study was to quantify the degree of aortoiliac
      tortuosity and determine the relationship between aortoiliac angulation and the
      need for a secondary procedure following endovascular repair. METHODS: Among 206
      patients treated with the AneuRx stent graft, 3-year follow up data were
      available in 71 patients. Twenty eight patients without duplex and CT angiograms
      (CT angiography) on follow-up were excluded. The anatomy of the preoperative
      proximal aortic neck was evaluated using 3D-CT angiography reconstructed images
      in: a) Group I: 15 patients who required secondary procedures and b) Group II: 18
      patients without any endovascular leak during follow up. The groups did not
      differ in age (72.9+/-6.1 versus 73.3+/-9.1) or aneurysm diameter (60.1+/-9.1
      versus 60.5+/-10.1). In order to determine the aortoiliac tortuosity, we
      measured: a) the suprarenal aorta-infrarenal aortic neck angle: angle of the
      aorta at the level of the renal arteries, b) infrarenal aortic neck-aneurysm
      angle: angle of the aorta at the start of aneurysm, c) right iliac angle, d) left
      iliac angle, e) aortic neck length, f) aortic neck diameter. RESULTS: Computer
      based measurements on 3D-CT angiography reconstructed images were: a) suprarenal
      aorta-infrarenal aortic neck angle: group I: (22.6+/-16.2), group II: (11.9+/
      6.9), p<0.05; b) infrarenal aortic neck-aneurysm angle: group I: 17.6+/-12.4,
      group II: 18.8+/-9.4, p=NS; c) right iliac angle: group I: 22.9+/-12.6, group II:
      20.4+/-9.5, p=NS; d) left iliac angle: group I: 22.4+/-10.5, group II: 19.1+/
      12.2, p=NS; e) aortic neck length: group I: 18.9+/-5.3 mm, group II: 20.4+/-5.3
      mm, p=NS; f) aortic neck diameter: group I: 24.1+/-1.0 mm, group II: 23.3+/-1.6,
      p=NS. CONCLUSIONS: Aortoiliac angulation can be defined and quantified. In
      patients requiring secondary procedures, there is an increased angulation at the
      proximal aortic neck angle.

PMID- 12518116
TI  - Hemorrheological variables in critical limb ischemia.
AB  - BACKGROUND: Impaired hemorrheological properties may worsen the tissue hypoxia
      distal to an arterial narrowing in patients with peripheral arterial occlusive
      disease (PAOD). The objective of this study was to investigate the changes in red
      blood cell rigidity, blood viscosity and plasma viscosity as contributing factors
      in the development of hypoxia in patients with critical limb ischemia (CLI).
      METHODS: Forty patients with critical limb ischemia and 40 healthy subjects were
      included in the study. The subjects included in the study were non-diabetic with
      blood pressure measurements within the normal range. Compound known to interfere
      with hemorrheological parameters were not taken by the patients for at least 7
      days prior to investigation. Routine blood counts (WBC, RBC, Hb, Hct), plasma
      fibrinogen levels, plasma total cholesterol levels, red blood cell rigidity,
      blood and plasma viscosity were determined in both groups. Statistical evaluation
      of the results of both groups was compared by student's "t"-test. The level of
      significance was set at p<0.05. RESULTS: Blood viscosity at a shear rate of 6.00
      sec(-1) was found to be significantly lower in the CLI group (p<0.001), whereas
      no significant difference was encountered when blood viscosity was measured at a
      shear rate of 225 sec(-1). Plasma viscosity and plasma fibrinogen levels were
      comparable. Plasma total cholesterol levels were found to be significantly higher
      in the CLI group (p<0.05) and red blood cell rigidity significantly lower
      (p<0.001). CONCLUSIONS: These findings may provide new insights into the role of
      blood viscosity in patients with CLI contrary to the previous reports in the
      literature. Therapies that address red blood cell rigidity more directly may
      decrease tissue hypoxia distal to arterial narrowing by preventing hemolysis,
      improving microcirculation, and increasing oxygen carrying capacity and may be
      more beneficial for these patients.

PMID- 12518117
TI  - Intermittent compression pump for nonhealing wounds in patients with limb
      ischemia. The Mayo Clinic experience (1998-2000).
AB  - BACKGROUND: The aim of this retrospective observational study was to review the
      use of an intermittent pneumatic compression device on nonhealing wounds in
      patients with critical limb ischemia at Mayo Clinic Rochester. METHODS: The
      setting was a community and referral multidisciplinary wound care clinic. The
      authors analysed 107 patients, median age 73, with critical limb ischemia and
      active ulcers started using a compression device between 1998 and 2000; 101
      patients had lower extremity ulcers, and 25% had a history of amputation, and 64%
      had diabetes. Of all the wounds, 64% were multifactorial in etiology, and 60% had
      associated transcutaneous oxygen tension levels below 20 mmHg. Patients were
      typically asked to use the device at home on the affected limb(s) for 6 hours
      daily. The main outcome criterion was complete wound healing with limb
      preservation. RESULTS: The median follow-up after initiation of treatment was 6
      months. Complete wound healing with limb preservation was achieved by 40% of
      patients with TcPO(2) levels below 20 mmHg; by 48% with osteomyelitis or active
      wound infection; by 46% with diabetes treated with insulin; and by 28% with a
      previous amputation. Half of all amputations occurred in patients with prior
      amputations. Seven patients discontinued the device because of pain experienced
      with its use. CONCLUSIONS: Patients with critical limb ischemia and nonhealing
      wounds at high risk of amputation can achieve complete wound healing and limb
      preservation by using an intermittent pneumatic compression device.

PMID- 12518118
TI  - Effect of artificial carbon dioxide foot bathing on critical limb ischemia
      (Fontaine IV) in peripheral arterial disease patients.
AB  - BACKGROUND: It has been reported that artificial carbon dioxide (CO(2)) foot
      bathing improves subcutaneous microcirculation in peripheral arterial disease
      (PAD) patients. However, the effect for critical limb ischemia (CLI) with
      ulceration or gangrene (Fontaine stage IV) is not identified. The physiological
      effects of CO(2) bathing and the outcome of limb salvage in such patients were
      studied. METHODS: In 18 healthy volunteers (Study I), the dorsal pedis peripheral
      blood flow was measured by a laser Doppler flow-meter during CO(2) foot bathing
      (1000 ppm, 37 degrees C) for 10 min. A Holter electrocardiogram was also
      recording in the same period. Blood flow and cell volume significantly increased
      during bathing. Eighty-three CLI limbs (Fontaine IV) in 68 PAD patients (Study
      II) underwent artificial CO(2) foot bathing (for 10 minutes twice daily >2
      months) were followed up >6 months. RESULTS: In Study I, analysis of heart rate
      variability showed that high frequency amplitude (HFA) considerably increased and
      the ratio of low frequency amplitude to HFA (LF/HF) noticeably decreased during
      bathing. In Study II, 69 limbs (83.1%) could be salvaged. Twenty-seven of 28
      limbs (96.4%) which have ulcer and gangrene in only one toe, 13/16 limbs (81.2%)
      in multiple toes and 29/39 limbs (74.4%) in all toes and/or heel respectively
      were saved. CONCLUSIONS: The effect of CO(2) enriched water on the subcutaneous
      microcirculation might be brought about by peripheral vasodilation reflected by
      increased parasympathetic and decreased sympathetic activity, and the artificial
      CO(2) foot bathing is clinically effective on salvage of CLI (Fontaine stage IV)
      limbs.

PMID- 12518119
TI  - A fast arterial duplex ultrasound performed by vascular surgeons. Is the time
      now?
AB  - BACKGROUND: With the technologic advancement in vascular ultrasound imaging,
      surgeons are now encouraged to perform their own examinations. Vascular surgeons
      run the vascular laboratory in the Suez Canal University hospital. The aim of
      this study is to determine the efficiency and advantages of arterial duplex
      scanning performed by the surgeon. METHODS: A prospective comparative study
      between the results of color duplex (performed by a vascular surgeon),
      arteriogram and operative finding in 105 limbs (96 lower and 9 upper) from 63
      patients, with chronic arterial occlusive disease or of peripheral arterial
      emergencies, was performed. The arterial vessels were divided into 13 segments.
      RESULTS: A total of 858 segments were examined. Duplex scanning was able to
      detect significant disease with a sensitivity of 83%, a specificity of 100%,
      positive predictive index 100%, negative predicative index 93%, accuracy 95% and
      k value of 0.85. Accuracy for the final therapeutic decision was 83% in
      arteriography, 80% in duplex and in a combination of both was 100%. CONCLUSIONS:
      Surgeon performed duplex is reliable and should be an integral part of the
      vascular surgeon's practice. Our practice recommends performing arteriography
      additionally in the lower limb to maximise preoperative information.

PMID- 12518120
TI  - Association of the HLA antigens with early atheromatosis in subjects with type 2
      diabetes mellitus.
AB  - BACKGROUND: Inflammation plays an important role in the pathogenesis of
      atherosclerosis. The major histocompatibility complex, as expressed by the human
      leukocyte antigens (HLA) is considered to regulate the immune response. The aim
      of this study was to investigate the association of the HLA antigens with
      vascular remodeling estimated by the carotid intima-media thickness (IMT) in
      subjects with type 2 diabetes mellitus (DM). METHODS: We evaluated 197 patients
      with type 2 DM, 80 males and 117 females, mean age 61.8+/-7.8 years, with no
      history of cardiovascular events. The presence of other major cardiovascular risk
      factors was recorded. The currently identified HLA class I (-A, -B, -Cw) and
      class II (DR, -DQ) antigens were studied by a classical 2 step
      microlymphocytotoxic technique in peripheral blood T and B lymphocytes.
      Measurements of the IMT were performed in the right and left common carotid
      arteries, 15-20 mm proximal to the dilatation of the carotid bulb in an end
      diastolic "frozen" and magnified B-mode ultrasonographic image. Glycosylated
      hemoglobin A1c (HbA1c) and C-reactive protein (CRP) were also measured. The
      results are presented as mean +/-1 standard deviation. RESULTS: Regarding the HLA
      phenotypes in the final analysis we tested a total of 24 HLA antigens that
      exhibited a frequency of at least 5% in our diabetic population. Only HLA A3 was
      found to be significantly associated with the carotid IMT. Forty-nine (24.9%)
      diabetics were HLA A3 positive (group A), while 148 (75.1%) were HLA A3 negative
      (group B) and had mean IMT of 0.89+/-0.16 mm and 0.98+/-0.21 mm, respectively
      (p<0.01). Also the two groups differed significantly in respect to CRP, with
      group A exhibiting lower serum levels (1.1+/-0.4 mg/dl vs 2.6+/-0.7 mg/dl for
      group A and B, respectively, p<0.05). However, no differences were observed
      between the two groups as far as blood glucose control, arterial hypertension and
      dyslipidaemia were concerned. CONCLUSIONS: Human leukocyte antigen A3 is
      associated with less vascular damage, as expressed by carotid wall thickness, in
      subjects with type 2 DM. These subjects may be characterized by a milder
      inflammatory response, as shown by the lower serum levels of CRP.

PMID- 12518121
TI  - The effect of lipoprotein-a on thrombolytic therapy and spontaneous reperfusion
      in acute myocardial infarction. A comparative study.
AB  - BACKGROUND: To evaluate the role of serum lipoprotein-a (Lp-a) levels on the
      success of thrombolytic therapy (TT) in patients with acute myocardial infarction
      (MI). METHODS:  PATIENTS: 56 patients randomly allocated into 2 groups (A and B)
      with an approximately 1 to 2 ratio. Group A consisted of 18 patients who received
      1,5 million IU streptokinase. Group B: 38 patients receiving 100 mg t-PA totally
      and Group C: 22 patients who did not received any TT as controls. All patients
      had undergone coronary angiography in the first 7 days and the degree of TIMI
      flow was determined in the infarct related artery with TIMI-0 and I being
      considered as unsuccessful perfusion, whereas TIMI-II and III as successful. Lp-a
      level gs;30 mg/dl was considered as high Lp-a level. RESULTS: Patency rates were
      similar in Group A and B, in cases with high or low Lp-a levels (p>0.05 for
      both). In Group C patency rate was found significantly higher in patients with
      high Lp-a level compared to patients with low Lp-a (p<0.01). Lp-a level in Group
      C was similar with Group A and B (p>0.05). The time interval for coronary
      angiography was similar in all groups (p>0.05 for all). CONCLUSIONS: Lp-a level
      does not effect the reperfusion outcome of TT in patients with MI. However in
      those patients who not received TT, spontaneous reperfusion rate was found
      significantly higher in patients with low Lp-a level compared to those with high
      Lp-a level.

PMID- 12518122
TI  - Transdermal glyceryl trinitrate for prevention of post-ERCP pancreatitis: A
      randomized double-blind trial.
AB  - BACKGROUND: Pancreatic sphincter hypertension increases the risk of pancreatitis
      in patients undergoing ERCP. Glyceryl trinitrate reduces sphincter of Oddi
      pressure. This study tested the hypothesis that transdermal glyceryl trinitrate
      could be effective in the prevention of post-ERCP pancreatitis. METHODS: One
      hundred forty-four patients undergoing ERCP were randomized: 71 received a 15-mg
      glyceryl trinitrate patch (glyceryl trinitrate group) and 73 a placebo patch
      (control group). RESULTS: In the control group, post-ERCP pancreatitis developed
      in 11 patients versus 3 in the glyceryl trinitrate group (p < 0.05). Twenty-four
      hour to baseline serum amylase and lipase ratios were lower in the glyceryl
      trinitrate group (respectively, 3.6 vs. 7.5, p < 0.05; and 5.3 vs. 27.7, p <
      0.05). In a multivariate analysis, glyceryl trinitrate patch and the number of
      pancreatic injections, but not endoscopic sphincterotomy, were independent risk
      factors for post-ERCP pancreatitis. CONCLUSIONS: The results of this study
      suggest that use of a transdermal glyceryl trinitrate patch protects against post
      ERCP pancreatitis.

PMID- 12518123
TI  - Systematic evaluation of complications related to endoscopy in a training
      setting: A prospective 30-day outcomes study.
AB  - BACKGROUND: The 30-day frequency of negative outcomes after outpatient endoscopy
      performed by gastroenterology fellows is unknown. METHODS: Questionnaires were
      mailed to 1000 consecutive patients 30 days after endoscopy to evaluate procedure
      related negative outcomes (serious and minor adverse events) and patient
      satisfaction. Serious adverse events were defined as follows: oversedation
      requiring administration of a reversal agent, and those that resulted in a
      physician visit, emergency department visit, admission to the hospital, or death.
      Minor adverse events were defined as all problems other than serious adverse
      events that patients related to their endoscopic procedure. RESULTS: The 30-day
      frequency of negative outcomes in the 869 patients who responded was 14.3%, of
      which 0.6% were serious and 13.7% were minor adverse events. The frequency of
      negative outcomes was 17.1% for EGD, 15.0% for colonoscopy, 24.4% for combined
      EGD and colonoscopy, and 7.8% for flexible sigmoidoscopy. One hundred percent of
      the serious adverse events were known to us, but only 16.0% of minor adverse
      events (p < 0.001). Multiple logistic regression identified midazolam dose (OR
      for each 1 mg increase in dose 4.5; 95% CI [2.7, 7.3]; p < 0.001), treatment with
      warfarin (OR 3.0; 95% CI [1.4, 6.2]; p = 0.003), comorbid disease (OR 2.1; 95% CI
      [1.3, 3.4]; p = 0.001), endoscopy performed in July or August (OR 2.0; 95% CI
      [1.1,3.7]; p = 0.02), and age (OR for each 1 year increase in age 1.03; 95% CI
      [1.01, 1.05]; p = 0.01) as independent predictors of negative outcomes. There was
      a significant association between negative outcomes and decreased patient
      satisfaction, and patients who reported negative outcomes were less likely to
      agree to endoscopy in the future. CONCLUSIONS: Serious adverse events were rare
      after endoscopy performed by gastroenterology fellows. Contacting patients 30
      days after outpatient endoscopy significantly improved the detection of negative
      outcomes. Although the majority of negative outcomes were minor, these adverse
      events were associated with decreased patient satisfaction.

PMID- 12518124
TI  - Radiofrequency energy delivery to the gastric cardia inhibits triggering of
      transient lower esophageal sphincter relaxation and gastroesophageal reflux in
      dogs.
AB  - BACKGROUND: Delivery of radiofrequency energy to the lower esophageal sphincter
      and gastric cardia is a new endoluminal technique proposed for the treatment of
      reflux disease. The mechanisms by which it achieves its effects are unclear. The
      study assessed the effect of radiofrequency energy delivery to the gastric cardia
      on the triggering of transient lower esophageal sphincter relaxations and
      gastroesophageal reflux in dogs. METHODS: In 13 dogs, esophageal motility and pH
      were measured for 1 hour after a standard liquid meal and air infusion, as well
      as before and 3 months after radiofrequency energy treatment. At 7 months,
      histologic evaluation of the gastroesophageal junction was performed. RESULTS:
      Radiofrequency energy delivery reduced the frequency of transient lower
      esophageal sphincter relaxations from 4.0 (3.0-6.75) (median [interquartile
      range]) per hour to 3.0 (2.0-3.0) per hour (p < 0.05). This was accompanied by a
      significant reduction in acid reflux episodes and esophageal acid exposure. Basal
      lower esophageal sphincter pressure and lower esophageal sphincter relaxation
      during swallowing were unchanged. There was a 63% increase in wall thickness at
      the gastric cardia compared with that in 2 control dogs, but no gross or
      histopathologic abnormalities of the esophageal or gastric mucosa. CONCLUSION:
      Radiofrequency energy delivery to the gastric cardia in dogs inhibits the
      triggering of transient lower esophageal sphincter relaxations and thereby
      reduces gastroesophageal reflux.

PMID- 12518126
TI  - Cost-effectiveness of pancreatic cancer screening in familial pancreatic cancer
      kindreds.
AB  - BACKGROUND: Endoscopic screening of families predisposed to pancreatic cancer is
      increasingly used, but the cost-effectiveness of screening is unknown. METHODS: A
      decision analysis was used to compare one-time screening for pancreatic dysplasia
      with EUS to no screening in a hypothetical cohort of 100 members of familial
      pancreatic cancer kindreds. Abnormal EUS findings are confirmed with ERCP and
      patients with abnormal findings are candidates for total pancreatectomy. Lifetime
      medical care costs and life expectancy were modeled, and the main analysis was
      conducted from the third-party payer perspective. The base-case analysis assumed
      a 20% prevalence of pancreatic dysplasia and 90% sensitivity of EUS and ERCP.
      RESULTS: Endoscopic screening was cost-effective, with an incremental cost
      effectiveness ratio of $16,885/life-year saved. Screening was more cost-effective
      as the probability of dysplasia increased and as the sensitivity of EUS and ERCP
      increased. Screening remained cost-effective if the prevalence of dysplasia was
      greater than 16% or if the sensitivity of EUS was greater than 84%. Procedure
      costs had a limited impact on cost-effectiveness. CONCLUSIONS: Endoscopic
      screening of carefully selected members of familial pancreatic cancer kindreds
      appears to increase patient life expectancy in a cost-effective manner. Screening
      should be performed in centers that have experience with endoscopic screening for
      pancreatic dysplasia. The cost-effectiveness of repeated screening remains to be
      determined.

PMID- 12518127
TI  - High-resolution EUS in children with eosinophilic "allergic" esophagitis.
AB  - BACKGROUND: The pathophysiology of dysphagia associated with eosinophilic
      esophagitis is unknown. This study investigated possible anatomic alterations in
      children with eosinophilic esophagitis in comparison with healthy children by
      using high-resolution EUS to precisely measure individual tissue layers of the
      esophagus. METHODS: Children with eosinophilic esophagitis (n = 11) and control
      children (n = 8) without esophagitis were prospectively evaluated by high
      resolution EUS with a 20-MHz catheter US probe during an endoscopic examination.
      Real-time measurements of the distal esophagus were obtained including the
      thickness of the total wall, combined mucosa and submucosa, muscularis propria,
      and circular muscle. RESULTS: Statistically significant differences were found
      between patients with eosinophilic esophagitis and control patients for mean
      values for thickness of the total wall (respectively, 2.8 vs. 2.1 mm; p = 0.004),
      combined mucosa and submucosa (respectively, 1.6 vs. 1.1 mm; p = 0.001), and
      muscularis propria (respectively, 1.2 vs. 1.0 mm; p = 0.043). Mean values for
      circular muscle did not differ between patient groups. CONCLUSION: High
      resolution EUS reveals significant expansion of the esophageal wall and
      individual tissue layers including the combined mucosa and submucosa, and
      muscularis propria in children with eosinophilic esophagitis compared with
      healthy control patients.

PMID- 12518128
TI  - An endoscopic pancreatic function test with synthetic porcine secretin for the
      evaluation of chronic abdominal pain and suspected chronic pancreatitis.
AB  - BACKGROUND: Pancreatic function tests are the most reliable methods for the
      diagnosis or exclusion of chronic pancreatitis in patients without obvious
      radiologic changes, but they are cumbersome, time consuming, and unavailable in
      clinical practice. Synthetic porcine secretin, a 27 amino acid peptide identical
      to the biologic form, is available for exocrine function testing. This study
      examined the utility of a simple, newly developed, purely endoscopic pancreatic
      function test with synthetic porcine secretin. METHODS: Three groups of patients
      were studied: patients with chronic abdominal pain with and without risk factors
      for chronic pancreatitis, and patients with advanced chronic pancreatitis. All
      patients with abdominal pain had "pancreatic type" pain for greater than 6 months
      and negative radiographic imaging studies. All patients with chronic pancreatitis
      had advanced disease based on retrograde pancreatography and/or CT findings.
      Participants underwent the following protocol: (1) standard endoscopy to the
      descending duodenum with the patient under conscious sedation; (2) intravenous
      administration of secretin (0.2 microgram/kg); (3) endoscopic duodenal fluid
      collection at 0, 15, 30, 45, and 60 minutes after secretin injection; and (4)
      fluid analysis for bicarbonate concentration. RESULTS: Eighteen patients were
      studied (5 abdominal pain without risk factors, 7 abdominal pain with risk
      factors, and 6 advanced chronic pancreatitis). Median peak (interquartile range)
      bicarbonate concentrations in meq/L for each group were, respectively, 87 (6,
      range 84-108), 72 (10, range 68-90), and 35 (27, range 18-88). Median peak
      bicarbonate concentration values for the 3 groups are significantly different (p
      = 0.010; Kruskal-Wallis test). Bicarbonate secretion in patients with chronic
      pancreatitis was markedly reduced compared with that in patients with abdominal
      pain without risk factors (p = 0.038; the Fisher exact test). The secretory
      function curve for patients with abdominal pain with risk factors was markedly
      abnormal, resembling the attenuated secretory curve seen in patients with chronic
      pancreatitis. The test was safe and well tolerated. CONCLUSIONS: A simple
      endoscopic pancreatic function test with synthetic porcine secretin appears to
      distinguish patients with known chronic pancreatitis from those with chronic
      abdominal pain without chronic pancreatitis. This simple, practical endoscopic
      test can be performed during upper endoscopy and may decrease the need for
      invasive procedures in patients with abdominal pain and normal radiographic
      imaging studies.

PMID- 12518129
TI  - Hydroxypropyl methylcellulose: A better submucosal fluid cushion for endoscopic
      mucosal resection.
AB  - BACKGROUND: Formation of a submucosal fluid cushion has become integral to
      endoscopic mucosal and polyp resection. Solutions available for injection into
      the submucosa of the GI tract create short-lasting submucosal fluid cushions or
      are costly. The feasibility, durability, and histologic response to submucosal
      fluid cushions created by injection of hydroxypropyl methylcellulose were studied
      in the esophagus of pigs. METHODS: Thirty-six esophageal submucosal fluid
      cushions created with hydroxypropyl methylcellulose were studied in 12 animals
      divided in 2 groups of 6 animals each. In Group I, 18 submucosal fluid cushions
      were created by submucosal injection of hydroxypropyl methylcellulose followed by
      tattooing. In Group II, 18 submucosal fluid cushions were created by submucosal
      injection of hydroxypropyl methylcellulose, with sites marked by an
      endoscopically placed suture. In all cases, the duration of the submucosal fluid
      cushion was measured. After 7 days, submucosal fluid cushion sites were assessed
      by EGD, necropsy, and histologic evaluation. RESULTS: The mean submucosal fluid
      cushion duration was 36 minutes (3-45 minutes) and 38 minutes (5-45 minutes) for,
      respectively, Groups I and II. EGD and necropsy after 1 week showed normal
      appearing mucosa at the site of all submucosal fluid cushions in both groups.
      Some Group I animals additionally had nodules at the tattoo sites. Histologic
      assessment demonstrated minimal alterations in 33 of 36 (92%) submucosal fluid
      cushion sites and localized mild inflammatory reaction in 3 of 36 (8%). In Group
      I, 8 of 18 (44%) tattoo sites exhibited a significant inflammatory reaction,
      including 3 abscesses. CONCLUSIONS: Hydroxypropyl methylcellulose creates a long
      lasting submucosal fluid cushion with minimal tissue reaction and should be
      considered a low-cost option for creating submucosal fluid cushions. The use of
      tattooing with carbon black should be carefully considered when histologic study
      is required to assess potential inflammatory tissue responses to an invasive
      technique or instillation of foreign material in the GI tract.

PMID- 12518131
TI  - Does insertion of a rectal tube after colonoscopy reduce patient discomfort and
      improve satisfaction?
AB  - BACKGROUND: Distention of the colon is a major contributor to patient discomfort
      after colonoscopy. Some physicians and nurses believe insertion of a rectal tube
      relieves this discomfort and improves patient satisfaction with the procedure.
      This prospective, randomized, controlled trial assessed rectal tube insertion for
      reduction or prevention of abdominal bloating and discomfort after colonoscopy.
      METHODS: One hundred fifty-seven patients were prospectively randomized to groups
      with (n = 68) and without (n = 89) rectal tube insertion after colonoscopy.
      Patients were evaluated for bloating, discomfort, and pain before the procedure,
      at its conclusion, at discharge, and 24 hours later (by telephone). Satisfaction
      was also assessed at discharge and 24 hours later. RESULTS: There were no
      differences between groups with respect to age, gender, hospitalization status,
      comorbidity, or socioeconomic status. In both groups the cecum was reached in 90%
      of patients and procedure time was similar. There were no differences between the
      groups in abdominal bloating (patient and nurse assessment), abdominal
      discomfort, or satisfaction at any time point. There were no serious
      complications. The subgroup of patients who experienced more severe pain and
      discomfort, regardless of whether a rectal tube was inserted, was characterized
      by more complaints of bloating, more incomplete procedures, and a higher rate of
      previous abdominal operations. CONCLUSIONS: Insertion of a rectal tube after
      colonoscopy does not affect abdominal bloating, pain, or discomfort during
      recovery from the procedure or over the subsequent 24 hours, nor does it affect
      overall patient satisfaction.

PMID- 12518130
TI  - A comparison of magnifying and nonmagnifying colonoscopy for diagnosis of
      colorectal polyps: A prospective study.
AB  - BACKGROUND: Discrimination between neoplastic and non-neoplastic colorectal
      polyps is essential for determining appropriate treatment. The mucosal crypt
      pattern of polyps can be observed with a nonmagnifying colonoscope; however,
      mucosal crypt patterns are better seen by magnifying colonoscopy, which can also
      be a noninvasive means for predicting histopathology. This study prospectively
      compared the ability to distinguish between neoplastic and non-neoplastic lesions
      by magnifying and nonmagnifying colonoscopy. METHODS: Six hundred sixty patients
      were randomly assigned to undergo magnifying or nonmagnifying colonoscopy (2
      groups each of 330 patients). The mucosal crypt pattern of colorectal lesions was
      classified into types I through V after spraying with 0.2% Indigo carmine dye.
      The histopathology of all lesions was confirmed by evaluation of endoscopic
      resection specimens or biopsy specimens. Only lesions 10 mm or less in diameter
      were included in the study. RESULTS: The accuracy of magnifying colonoscopy in
      distinguishing neoplastic from non-neoplastic lesions (92%, 372/405) was
      significantly higher than for nonmagnifying colonoscopy (68%, 278/407). Insertion
      of magnifying and nonmagnifying colonoscopes to the cecum was successful in,
      respectively, 321 patients (97%) and 317 patients (96%), with no significant
      differences in the average time to reach the cecum or average total procedure
      time. No serious complication was observed during or immediately after the
      examinations. CONCLUSIONS: Observation of mucosal crypt pattern with magnifying
      colonoscopy is superior to nonmagnifying colonoscopy for distinguishing between
      neoplastic and non-neoplastic colorectal lesions.

PMID- 12518132
TI  - Endotracheal intubation for airway protection during endoscopy for severe upper
      GI hemorrhage.
AB  - BACKGROUND: Aspiration of blood may cause significant morbidity during emergent
      endoscopy for severe upper GI bleeding. Endotracheal intubation is widely
      performed for airway protection in this setting, but there are few data regarding
      its efficacy. METHODS: Outcomes were compared for intensive care unit patients
      with upper GI bleeding for 1 year (1988) during which prophylactic endotracheal
      intubation was seldom performed before endoscopy, with outcomes during a
      subsequent year (1992) in which endotracheal intubation was routine for airway
      protection before or during EGD when there was hematemesis, altered mentation,
      unstable cardiopulmonary status, or large amounts of blood in the proximal GI
      tract, or before endoscopic treatment of lesions at high risk for bleeding.
      RESULTS: Background variables were similar for intensive care unit patients in
      1988 (n = 101) and 1992 (n = 119) with respect to number of patients who had
      shock (respectively, 66.3% vs. 67.2%), cirrhosis (34.7% vs. 38.6%),
      variceal/portal hypertensive bleeding (22.8% vs. 33.6%), and endoscopic therapy
      (37.6% vs. 42.0%). Although use of endotracheal intubation specifically for EGD
      increased significantly between 1988 and 1992 (3.0% vs. 15.1%; p < 0.05), there
      were no significant changes in endotracheal intubation at any time during
      hospitalization (24.8% vs. 28.6%), in all EGD-related cardiopulmonary
      complications (5.0% vs. 3.4%), in new pulmonary infiltrates after EGD (12.9% vs.
      15.1%), in mean number of intensive care unit days (7.1 vs. 6.4), or in mortality
      (15.9% vs. 11.8%). New infiltrates developed in 10 (48%) of 21 patients after EGD
      despite endotracheal intubation specifically for airway protection. However, in
      1992 there were no fatal episodes of aspiration during EGD (2.0% vs. 0%; p =
      0.21), no emergent post-EGD endotracheal intubation (6.0% vs. 0%; p < 0.05), and
      fewer in-hospital cardiopulmonary arrests (12.9% vs. 5.0%; p < 0.05). CONCLUSION:
      Frequent use of endotracheal intubation for airway protection during EGD for
      upper GI bleeding requiring intensive care unit admission did not significantly
      change the relatively high frequency of acquired pneumonia or cardiopulmonary
      events, but may have prevented the rare fatal episode of massive aspiration.
      Endotracheal intubation may benefit selected patients with upper GI bleeding, but
      its specific role remains unclear, and alternative methods of airway protection
      should be investigated.

PMID- 12518133
TI  - Outcome of endoscopic treatment for peptic ulcer bleeding: Is a second look
      necessary? A meta-analysis.
AB  - BACKGROUND: Endoscopic therapy for GI bleeding is highly effective. Nevertheless,
      bleeding recurs in 10% to 25% of cases, irrespective of the method of treatment
      used. Whether a second-look endoscopy with retreatment after initial hemostasis
      is of clinical value is controversial. A meta-analysis was performed to assess
      whether systematic second-look endoscopy with retreatment reduces the risks of
      recurrent bleeding, salvage surgery, and death in patients with peptic ulcer
      bleeding. METHODS: A systematic review was performed of randomized controlled
      studies of the value of second-look endoscopy in patients with peptic ulcer
      bleeding published between 1990 and 2000. Four studies were selected according to
      predefined criteria. Two investigators extracted the data independently. Pooled
      risk estimates and number need to treat were calculated for each procedure.
      Heterogeneity of effects was tested. RESULTS: The absolute risk reduction in
      clinical recurrent bleeding was 6.2% (p < 0.01). Absolute risk reduction for
      surgery and mortality were, respectively, 1.7% and 1.0% (not significant). The
      second look with retreatment significantly reduced the risk of recurrent bleeding
      compared with control patients (OR 0.64; 95% CI [0.44, 0.95]; p < 0.01), with a
      number needed to treat of 16. There was no heterogeneity among studies. The risk
      of surgery as well as the risk of death were not significantly influenced by the
      second-look endoscopy with retreatment (number needed to treat, respectively, 58
      and 97). CONCLUSIONS: Systematic second-look endoscopy with retreatment
      significantly reduces the risk of recurrent bleeding in patients with peptic
      ulcer bleeding compared with control patients, but it does not substantially
      reduce the risk of salvage surgery or mortality.

PMID- 12518134
TI  - Yield of tissue sampling for submucosal lesions evaluated by EUS.
AB  - BACKGROUND: Evaluation of submucosal nodules or large gastric folds is a common
      indication for EUS. Establishing a tissue diagnosis is challenging because the
      yield of forceps biopsies is low. The aim of this study was to determine the
      diagnostic yield of EUS-guided endoscopic submucosal-mucosal resection and
      forceps biopsy for submucosal nodules and large gastric folds. METHODS: Patients
      who underwent EUS from March 1997 through January 2002 for evaluation of
      submucosal nodules or large gastric folds were identified, and the procedure and
      pathology reports reviewed. Patients were included who underwent endoscopic
      submucosal-mucosal resection (n = 45) or large-capacity ("jumbo") biopsy (n = 36)
      of submucosal lesions (arising from third endosonographic layer) or large gastric
      folds. Endoscopic submucosal-mucosal resection was performed with an
      electrosurgical snare or with a cap-fitted endoscopic mucosal resection device.
      RESULTS: Sixty-six patients (62% men; mean age, 61 years; range 27-80 years)
      underwent 69 EUS procedures to obtain tissue samples of subepithelial lesions.
      Diagnostic yields were as follows: endoscopic submucosal-mucosal resection 40/45
      (89%; 95% CI [80%, 98%]), jumbo biopsy 15/36 (42%; 95% CI [26%, 58%]) (p < 0.001
      by two-tailed Fisher exact test). There were 9 complications: 7 instances of
      bleeding (6 endoscopic submucosal-mucosal resection, 1 jumbo biopsy), 3 requiring
      hospitalization (2 endoscopic submucosal-mucosal resection, 1 jumbo biopsy) and 2
      requiring transfusion; 1 chest pain and odynophagia (esophageal endoscopic
      submucosal-mucosal resection); and 1 oversedation (requiring administration of
      reversal agents). CONCLUSIONS: For submucosal lesions and large gastric folds,
      endoscopic submucosal-mucosal resection has a better diagnostic yield than the
      jumbo biopsy, but may have a higher complication rate.

PMID- 12518135
TI  - Development of a swine model for benign stenosis of the bile duct by endoscopic
      application of intraluminal thermal injury.
AB  - BACKGROUND: A simple animal model is desirable for the study of endoscopic
      therapies used in the management of biliary strictures. The aim of this study was
      to identify a method for inducing benign biliary stenoses in a porcine model by
      using endoscopic techniques. METHODS: Endoscopic retrograde cholangiography was
      performed in 9 swine. Intraluminal injury was applied to the common hepatic duct
      with graded applications of either a heat probe or a multipolar probe.
      Cholangiography was repeated at 7-day intervals. If a stricture was not
      identified by 28 days, injury was created at another site in the common hepatic
      duct by using a higher energy dose. After a stricture was identified, the animal
      was killed and bile duct samples were obtained for histopathologic evaluation.
      RESULTS: Thirteen thermal injuries were created in the 9 animals. Six of 7 heat
      probe treatments and 1 of 6 multipolar probe treatments resulted in a stricture
      (p = 0.025, Fisher exact test). Applications of the heat probe at 10 or 15 J
      produced a stricture in 6 of 6 cases. All strictures were indistinguishable
      histopathologically from benign strictures in humans. CONCLUSIONS: The
      application of intraluminal thermal injury with a heat probe results in a
      reproducible animal model of benign biliary stenosis.

PMID- 12518136
TI  - Efficacy of endoscopic and percutaneous treatments for biliary complications
      after cadaveric and living donor liver transplantation.
AB  - BACKGROUND: Percutaneous transhepatic radiologic procedures as well as ERCP-based
      techniques have been used to treat biliary complications after liver
      transplantation. However, the efficacy of these treatments has not yet been
      clarified, especially for complications occurring after living donor liver
      transplantation. METHODS: A retrospective study was performed to determine the
      frequency and types of the biliary complications after cadaveric donor liver
      transplantation and living donor liver transplantation. The success of ERCP and
      percutaneous transhepatic radiologic procedures was also evaluated. The choice of
      treatment approach, ERCP or percutaneous transhepatic radiologic procedures,
      depended on the type of biliary reconstruction and accessibility of the lesion.
      RESULTS: Among 429 adult patients who underwent liver transplantation, 39 biliary
      complications developed in 25 patients (5.8%): biliary stricture (20), biliary
      stones (10), and bile leak (9). The frequency of biliary complications (5.8%;
      6/103) after cadaveric donor liver transplantation was not significantly
      different compared with that after living donor liver transplantation (5.8%;
      19/326). Success rates for treatment of biliary complications by means of ERCP
      and percutaneous transhepatic radiologic procedures were, respectively, 100%
      (11/11) and 78% (18/23). For endoscopically treated patients, balloon dilation
      alone for biliary strictures and nasobiliary tube placement alone for bile leaks
      resulted in complete resolution of the complication in, respectively, 67% (2/3)
      and 40% (2/5) without further intervention. CONCLUSIONS: Transpapillary
      endoscopic and percutaneous transhepatic radiologic interventions are both
      effective therapies for biliary complications associated with liver
      transplantation. They are complementary approaches that help to avoid surgery for
      these complications.

PMID- 12518137
TI  - Bariatric surgery: Creating new challenges for the endoscopist.

PMID- 12518138
TI  - Villous adenoma of entire biliary tree.

PMID- 12518139
TI  - Mucosal bridging.

PMID- 12518140
TI  - Duodenal lymphangiectatic cyst.

PMID- 12518141
TI  - Ileal adenoma.

PMID- 12518142
TI  - Pseudocholangiocarcinoma caused by right hepatic artery aneurysm.

PMID- 12518143
TI  - Synchronous esophageal squamous carcinomas.

PMID- 12518144
TI  - Preliminary experience with an EUS-guided trucut biopsy needle compared with EUS
      guided FNA.
AB  - BACKGROUND: EUS-guided FNA is a sensitive method for the diagnosis of malignancy.
      However, EUS-FNA is often laborious and usually requires the presence of a
      cytopathologist or cytotechnician. The development of an EUS-guided Trucut biopsy
      (EUS-TCB) needle may simplify the procedure and expand the application of EUS
      directed procurement of biopsy specimens. The aim of this study was to determine
      the feasibility of using the EUS-TCB for the diagnosis of intraintestinal and
      extraintestinal lesions and compare the results with this needle with those of
      EUS-FNA. METHODS: The EUS-TCB and EUS-FNA were used to evaluate patients with
      known or suspected intraintestinal or extraintestinal mass lesions and/or
      lymphadenopathy. Patient records were retrospectively reviewed to determine the
      accuracy and safety of both techniques. RESULTS: Nineteen patients had tissue
      samples obtained with both the EUS-TCB and EUS-FNA from 20 sites (2 sites in 1
      patient) between December 2001 and March 2002. Accuracy was higher with EUS-TCB
      than EUS-FNA, although the difference was not significant (85% vs. 60%), despite
      performing fewer passes with the former (mean [SD] 2.0 [0.7], range 1-4; vs. mean
      3.3 [1.5], range 1-10; p < 0.05). No complications were identified. CONCLUSIONS:
      This preliminary study suggests EUS-TCB can safely be used to obtain biopsy
      specimens of intraintestinal and extraintestinal mass lesions and
      lymphadenopathy. Its use may reduce the number of needle passes compared with EUS
      FNA. This may reduce costs by shortening the procedure, diminishing the need for
      an onsite cytopathologist or technician, and lowering the frequency of
      nondiagnostic procedures. Prospective studies are needed to verify these
      findings.

PMID- 12518145
TI  - Endoscopically inserted endoluminal receiver coil for high-resolution magnetic
      resonance imaging of the pancreas: Initial results in an animal model.
AB  - BACKGROUND: This study assessed the feasibility of high-resolution magnetic
      resonance imaging of the pancreas by means of an endoscopically inserted
      endoluminal magnetic resonance receiver coil. METHOD: A 0.032-inch diameter
      internal magnetic resonance imaging receiver coil was endoscopically inserted
      into the pancreatic duct in 4 pigs through the accessory channel of a standard
      duodenoscope to obtain high-resolution magnetic resonance images by using T1- and
      T2-weighted sequences. RESULTS: The pig anatomy precluded the usual transoral
      approach; however, transgastric access allowed endoscopic transpapillary
      insertion of a receiver coil into the pancreatic duct in all animals without the
      need for sphincterotomy. The small swine pancreas could then be visualized by
      magnetic resonance imaging with a 0.3 x 0.3-mm in-plane resolution. CONCLUSION:
      High-resolution pancreas magnetic resonance imaging is feasible by using an
      endoscopically inserted endoluminal receiver coil. The smaller stomach and larger
      pancreatic duct diameter in humans will facilitate clinical application of the
      imaging procedure.

PMID- 12518146
TI  - Argon plasma coagulation: Clinical experience in pediatric patients.
AB  - BACKGROUND: Argon plasma coagulation has potential advantages in pediatric
      endoscopy. METHODS: Argon plasma coagulation was applied in 13 children (age 0.05
      17 years; median 3 years) with significant comorbid conditions including
      immunosuppression, chemotherapy, acute or chronic organ failure, and
      coagulopathy. Twelve had bleeding lesions; esophageal granulomatous tissue was
      coagulated in one. The bleeding lesion was located in the stomach in 9 of 12, the
      duodenum in 2 of 12 (both with granulomatous tissue), and at an enterocolonic
      anastomosis in 1 of 12. OBSERVATIONS: In total, 23 procedures were performed, 22
      for bleeding (range 1-5 per patient). Hemostasis was achieved in 8 of 12 with one
      session. Blood loss and transfusion requirement were reduced in 3 of the other 4
      patients. Blood loss was not affected in 1. Bleeding recurred in 3 of 12, and
      additional procedures were performed in 7 of 12. Granulomatous tissue was
      completely eradicated in 2 of 3; in one, granulomatous tissue associated with
      surgical staples was only partially removed. Complications occurred in 2 of 13
      patients and included submucosal argon gas and scar formation. CONCLUSION:
      Endoscopic argon plasma coagulation is efficacious for hemostasis and tissue
      ablation in pediatric patients. Minor complications occurred in 17% (2/13) of
      cases in this series.

PMID- 12518147
TI  - EUS-guided ethanol injection for treatment of a GI stromal tumor.

PMID- 12518148
TI  - Duodenal diverticular hemostasis with hemoclip placement on the bleeding and
      feeder vessels: A case report.

PMID- 12518149
TI  - Triad of sclerosing cholangitis, chronic pancreatitis, and Sjogren's syndrome:
      Case report and review.

PMID- 12518150
TI  - Synchronous and metachronous small bowel adenocarcinomas in a patient with celiac
      disease.

PMID- 12518151
TI  - Complex colovesicular fistula: A severe complication caused by biliary stent
      migration.

PMID- 12518152
TI  - Endoscopic removal of a snare entrapped around a polyp by using a dual endoscope
      technique and needle-knife.

PMID- 12518153
TI  - Elongated non-neoplastic duodenal polyp: Endoscopic features.

PMID- 12518154
TI  - Gastric heterotopia in the proximal esophagus complicated by stricture.

PMID- 12518155
TI  - Stroke caused by cerebral air embolism during endoscopy.

PMID- 12518156
TI  - Duodenoscrotal fistula secondary to retroperitoneal migration of an
      endoscopically placed plastic biliary stent.

PMID- 12518158
TI  - Esophagitis dissecans superficialis associated with celiac disease.

PMID- 12518157
TI  - Fractured esophageal nitinol stent: Report of two fractures in the same patient.

PMID- 12518159
TI  - From major to minor: Are all endoscopic complications created equal?

PMID- 12518160
TI  - Wanted: A few good (young) investigators.

PMID- 12518161
TI  - Latin-American gastrointestinal endoscopy training center.

PMID- 12518162
TI  - Trans-PEG ultra thin endoscopy for PEG/J Placement.

PMID- 12518163
TI  - What is the best method of treatment for gastric fundal varices without active
      bleeding?

PMID- 12518164
TI  - Can you catch Behcet's disease?

PMID- 12518165
TI  - Recent advances in allogeneic hematopoietic stem-cell transplantation.

PMID- 12518166
TI  - Expansion of gammadelta T-cells in Behcet's disease: role of disease activity and
      microbial flora in oral ulcers.
AB  - Gammadelta T-cells participate in the immune response to infections and in
      autoimmunity by recognizing bacteria-derived and autologous antigens. The goal of
      this study was to evaluate the involvement of gammadelta T-cells in Behcet's
      disease (BD). Gammadelta T-cells in the peripheral-blood mononuclear cells
      (PBMCs) of Israeli patients with definite BD (n = 23), normal controls (n = 16),
      and patients with familial Mediterrranean fever (FMF; n = 20) were evaluated by
      means of flow cytometry. The responses of patient and control gammadelta T-cells
      to medium conditioned by microorganisms cultured from an oral ulcer of a patient
      with active BD were compared. The proportions of CD3(+) and CD8(+) cells in the
      PBMCs were not significantly different between groups. In contrast, gammadelta-T
      cells accounted for 7.01% +/- 4.42% of the PBMCs in BD compared with 3.56% +/-
      3.45% in FMF (P < .005) and 3.7% +/- 3.15% in normal individuals (P < .009).
      Their numbers were significantly higher during active disease than in remission
      (9.45% +/- 5.08% versus 2.27% +/- 3.3%; P < .009). The number of T-cell-receptor
      gammadelta(+) and Vdelta2(+) cells of BD patients, but not of controls, increased
      after 96 hours of culture in medium containing supernatant of microorganisms
      cultured from an oral ulcer in a patient with BD relative to their proportions in
      control medium: 58.2% vs 13.9% (P < .05) and 28% vs 9% (P < .04), respectively,
      of the cultured T-cells (n = 4).gammadelta T-cells are expanded in BD PBMCs
      during active disease. An exaggerated proliferative response to products released
      by microorganisms present in oral ulcers may play a role in this phenomenon.

PMID- 12518167
TI  - Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in
      health.
AB  - Oxidation of low-density lipoprotein (LDL) and hyperhomocysteinemia are believed
      to play a role in therogenesis. Whether n-3 polyunsaturated fatty acids increase
      LDL susceptibility to oxidation or influence homocysteine (Hcy) metabolism has
      long been a subject of controversy. In this study, we evaluated the effect of 8
      weeks of dietary supplementation with 6 g/day of fish oil (FO; 3 g of n-3 fatty
      acids) on plasma lipoproteins, in vitro LDL peroxidation, antioxidant status, and
      plasma Hcy concentrations in 16 normolipidemic subjects. FO rapidly and
      significantly (P < .01) decreased plasma total and very low density lipoprotein
      triglyceride concentrations and had no effect on LDL or high-density-lipoprotein
      cholesterol. The mean lag time before onset of Cu(2+)-induced LDL oxidation, as
      well as plasma and LDL alpha-tocopherol and beta-carotene concentrations, was
      unchanged. However, changes in plasma aminothiol concentrations occurred during
      the study. Specifically, a progressive and significant increase in total Hcy
      plasma concentrations was observed (13.4% and 20% after 4 and 8 weeks,
      respectively; P < .01). Total glutathione concentrations were significantly
      higher after 8 weeks (P < .05). The tHcy increase was not associated with changes
      in plasma folate or vitamin B(12) concentrations. However, concentrations of
      plasma nitric oxide metabolites (NO(x) = NO(2) + NO(3)) were significantly higher
      than at baseline after 8 weeks of FO intake (74%; P < .01). Further, the changes
      in total Hcy and NO(x) plasma concentrations observed after 8 weeks of FO were
      found to be significantly correlated (r = .78, P < .001). With this study, we
      report for the first time the apparent interaction of n-3 fatty acids and nitric
      oxide on Hcy metabolism.

PMID- 12518168
TI  - Laser-light scattering, a new method for continuous monitoring of platelet
      activation in circulating fluid.
AB  - We evaluated a novel technique of laser-light scattering (LLS) to detect platelet
      volume changes continuously, reflecting platelet aggregation in circulating
      fluid. Carotid arteries from 20 dogs were mounted in a dual perfusion chamber.
      Balloon angioplasty (BA) was performed and arteries perfused with platelet-rich
      plasma (PRP). A He-Ne laser beam was passed through cuvettes connected to tubing
      draining the arteries. From the angle of incidence, the average volume of
      aggregates was measured by the ratio of scattering light at 1 to 5 degrees'
      spread on the diode array of a multichannel analyzer. Platelet volume varied
      linearly with the scattered light ratio at 1 to 5 degrees (y = -24.2 + 27.6 x [y
      = particle size, microm(3); x = scattered light ratio at 1/5 degrees]). For
      comparison, we used an electronic particle counter (Coulter counter) to measure
      platelet volume. P-selectin expression was measured to confirm platelet
      activation. Comparing 10 uninjured and 10 BA-injured arteries, we found that
      platelet volume as measured with LLS increased from 21.6 +/- 4.1 to 52.1 +/- 12.5
      microm(3) (P < .003); as measured with the Coulter counter, it increased from
      29.9 +/- 2.4 to 62.3 +/- 7.0 microm(3) (P < .005). Six BA-injured arteries
      perfused with PRP and aspirin (0.2 mg/mL) were compared with six arteries treated
      with BA alone. The aspirin decreased platelet volume as measured with LLS from
      56.2 +/- 11.8 to 40.2 +/- 12.7 microm(3) (P < .01); the Coulter counter revealed
      a decrease from 51.9 +/- 18.5 to 38.8 +/- 14.2 microm(3) (P < .001). Coulter
      counter and LLS results were correlated: r = 0.74, P < .05. The peak of P
      selectin expression coincided with peak platelet volume. These data demonstrate
      that increases in circulating-platelet size stimulated by endovascular injury can
      be reliably and continuously monitored with the use of LLS.

PMID- 12518169
TI  - 9-cis retinoic acid enhances the antiviral effect of interferon on hepatitis C
      virus replication through increased expression of type I interferon receptor.
AB  - The concentration of type I interferon receptor (IFN-Rc) in the liver is a
      crucial factor in determining the efficacy of interferon (IFN) therapy in
      patients with chronic hepatitis C. Retinoic acids (RAs) can enhance the
      expression of type I IFN-Rc expression. The aim of this study was to investigate
      whether RAs increase the anti-hepatitis C virus (HCV) effect of IFN through an
      increase in IFN-Rc. The hepatocellular carcinoma cell line HuH-7 was treated with
      10(-7) mol/L all-trans RA (ATRA) and 9-cis RA (9-CRA). Expression of type I IFN
      Rc was investigated at both the mRNA and protein levels with the use of real-time
      quantitative polymerase chain reaction and flow cytometry, respectively. We
      investigated the anti-HCV effect, using in vitro HCV transfection, by monitoring
      the level of HCV RNA in the culture medium. ATRA and 9-CRA enhanced the
      expression of type I IFN-Rc at both the mRNA and protein levels. After IFN-alpha
      treatment, the activity of 2,5'-oligoadenylate synthetase was enhanced by RAs,
      and this enhancement was abolished when blocking antibodies had previously been
      bound to the surface receptors. IFN treatment decreased the concentration of HCV
      RNA, and this effect was enhanced by treatment with RAs. Our findings suggest
      that RAs enhance the anti-HCV replication effect of IFN-alpha through up
      regulation of type I IFN-Rc in HuH-7 cells.

PMID- 12518170
TI  - ATP protects, by way of receptor-mediated mechanisms, against hypoxia-induced
      injury in renal proximal tubules.
AB  - We examined the effect of ATP on hypoxia-induced injury in freshly isolated rat
      renal proximal tubules and compared it with the effects of stable ATP analogues
      and ATP degradation products. Extracellular ATP significantly reduced hypoxia
      induced structural cell damage (lactate dehydrogenase release). P(2)-receptor
      agonistic ATP analogues, including 2'-methylthio-ATP (2-Me-S-ATP), were also
      protective. In contrast, the P(1)-agonistic degradation products AMP and
      adenosine were not protective. Hypoxia-induced functional cell damage (loss of
      cellular potassium) was not changed by ATP or 2-Me-S-ATP. We therefore conclude
      that the protective property of ATP is not based on an effect of the degradation
      products or on a direct effect on cellular energy metabolism. The data indicate
      that the protective effect of ATP is mediated by P(2) receptors.

PMID- 12518171
TI  - H1-A extracted from Cordyceps sinensis suppresses the proliferation of human
      mesangial cells and promotes apoptosis, probably by inhibiting the tyrosine
      phosphorylation of Bcl-2 and Bcl-XL.
AB  - H1-A, a pure compound used in traditional Chinese medicine, is effective in the
      treatment of autoimmune disorders of MRL lpr/lpr mice. We have previously
      reported that after 8 weeks of oral therapy with H1-A, 40 microg/kg/day, MRL
      lpr/lpr mice demonstrated significantly less proteinuria, lower serum creatinine
      levels, and less renal mesangial proliferation than mice in an untreated group.
      To clarify the pharmacologic properties of H1-A, we studied its cellular and
      subcellular effects in cultured human mesangial cells. Our results show that H1-A
      inhibits cell proliferation and promotes the apoptosis of interleukin (IL)-1- and
      platelet-derived growth factor (PDGF)-BB-activated human mesangial cells in
      vitro. Uptake of tritiated thymidine was nearly totally suppressed by the
      addition of 12.5 micromol/L H1-A (counts per minute decreased from 3905 +/- 70 to
      141 +/- 5). The population of S-phase cells decreased from 15.5% +/- 1.7% to
      10.0% +/- 0.3%, and G0 + G1 phase cells increased from 68.8% +/- 0.07% to 74.6%
      +/- 0.05%. This suppression was not a result of cytotoxicity. Apoptosis of human
      mesangial cells was detectable after treatment with 12.5 or 25 micromol/L H1-A.
      Using immunoprecipitation and immunoblotting, we found that H1-A inhibits
      tyrosine phosphorylation of human mesangial proteins and that Bcl-2 and Bcl-XL
      were probably among these proteins. These findings suggest that H1-A modulates
      some subcellular signal-transduction pathways and changes the balance between
      proliferation and apoptosis of mesangial cells in vitro or in vivo. H1-A may be
      effective in the management of autoimmune disorders, and the modulation of the
      signal transduction proteins Bcl-2 and Bcl-XL may represent a target for future
      pharmacologic interventions.

PMID- 12518172
TI  - Persistent pain prevalence and medical management.

PMID- 12518173
TI  - Nerve blocks and cognitive therapy: a beneficial failure.

PMID- 12518174
TI  - Chronic pain in Canada--prevalence, treatment, impact and the role of opioid
      analgesia.
AB  - OBJECTIVE: To assess the prevalence, treatment and impact of chronic pain in
      Canada. METHODS: A stratified random sample of 2012 adult Canadians (weighted by
      sex, age and region according to 1996 census data) was surveyed by telephone in
      2001 to determine the prevalence of chronic pain, defined as continuous or
      intermittent pain for at least six months. A second sample of 340 chronic pain
      sufferers who were taking prescription medication for their pain was studied in
      detail to determine current therapeutic approaches and to assess the social and
      economic impact of chronic pain. RESULTS: Chronic noncancer pain was reported by
      29% of the respondents, with increased frequency in women and older age groups.
      The average duration of pain was 10.7 years and the average intensity was 6.3 (on
      a scale from 1 to 10), with 80% reporting moderate or severe pain. Anti
      inflammatory agents were prescribed for 49% of respondents and opioid analgesics
      were prescribed for 22% (two-thirds of these were codeine). Almost 70% were
      worried about addiction potential, and one-third felt that strong analgesics
      should be reserved for terminal illnesses. Almost one-half were unable to attend
      social and family events, and the mean number of days absent from work in the
      past year due to chronic pain was 9.3. INTERPRETATION: Chronic noncancer pain is
      common in Canadian adults and has a major social and economic impact. Despite
      growing evidence supporting the efficacy and safety of major opioid analgesics
      for chronic noncancer pain, less than 10% of chronic pain patients taking
      prescription medication were treated with a major opioid. Chronic pain is
      undertreated in Canada, and major opioid analgesics are probably underutilized in
      the management of moderate to severe pain as part of a multidisciplinary
      treatment program.

PMID- 12518175
TI  - A randomized treatment study to compare the efficacy of repeated nerve blocks
      with cognitive therapy for control of chronic head and neck pain.
AB  - This prospective study compared the efficacy of two antinociceptive modalities:
      nerve blocks and cognitive therapy. A consecutive series of patients receiving
      nerve block therapy was invited to take part in a six-week randomized comparison
      of nerve blocks and cognitive therapy. Sixty-eight of 102 patients approached by
      telephone agreed to participate. Patients attended eight weekly treatment
      sessions. Baseline and seven weekly sets of values were recorded. The principal
      measure of outcome was the Pain on a Visual Analogue Scale (VAS). The secondary
      measures were the Hospital Anxiety and Depression Scale, and the Activities of
      Daily Living as measured on the Primary Care Cooperative Information
      Project/World Organization of National Colleges, Academies (COOP-WONCA) scale.
      Within the first week, one patient of 34 in the nerve block group withdrew and 12
      of 34 in the cognitive therapy group withdrew from the study. After seven weeks,
      33 patients in the nerve block group remained in the trial, but only 21 patients
      completed the questionnaires. Four of 22 patients in the cognitive therapy group
      completed the trial and their questionnaires. Mean VAS scores in the nerve block
      group dropped slightly during treatment. Mean VAS scores in the cognitive therapy
      group rose during the trial. However, the mean VAS score of the remaining four in
      the last week was below the initial group mean. Patients who had been receiving
      nerve blocks proved willing to remain in the study if allocated to the nerve
      block group and unwilling to remain in the cognitive therapy group while
      foregoing their accustomed treatment.

PMID- 12518176
TI  - Interpreting the meaning of pain severity scores.
AB  - Poor pain management practices are generally discussed in terms of barriers
      associated with the patient, clinician and/or health care organization. The
      impact of deficiencies in the tools that are used to measure pain are seldom
      addressed. Three factors are discussed that complicate the measurement of pain:
      the nature of pain, the lack of meaning associated with scores generated by pain
      scales, and treatment goals that lack specificity and are not linked to patients'
      pain scores. The major premise presented in the present article is that the
      utility of pain measurement is limited because health care professionals do not
      have a common understanding of the meaning of scores generated by pain
      measurement tools, especially within the acute care setting. To address this
      issue, approaches to establishing instrument validity need to be broadened to
      include the examination of the meaning and consequences of these measurements
      within a specific context. Substantive improvements in pain management are
      unlikely to occur until criteria are identified to link explicitly the scores
      generated by pain measurement tools to treatment goals.

PMID- 12518177
TI  - Patients' attitudes and prior treatments in neuropathic pain: a pilot study.
AB  - BACKGROUND: Ongoing research continues to expand the knowledge of neuropathic
      pain. It is vital that established treatments and valuable discoveries ultimately
      improve patient care. OBJECTIVES: Attitudes and prior treatments of patients
      being screened for neuropathic pain trials were evaluated to provide further
      understanding of the barriers to the management of neuropathic pain. METHODS: A
      questionnaire was completed by patients with neuropathic pain who were either
      referred by local physicians or self referred in response to clinical trial
      advertisements from the authors' facility. RESULTS: In total, 151 patients
      completed the questionnaire. Diagnoses included diabetic neuropathy (55.6%),
      postherpetic neuralgia (29.8%), idiopathic peripheral neuropathy (9.3%) and
      others (5.3%). The mean pain duration was 4.7 years, and the mean daily pain (on
      a score of 0 to 10) was 7.6. During questioning, 72.8% complained of inadequate
      pain control and 25.2% had never tried any antineuropathic analgesics (tricyclic
      antidepressants, opioids or anticonvulsants). New antineuropathic analgesics (eg,
      gabapentin) were being used by only 16.6%. Opioids, tricyclic antidepressants and
      anticonvulsants had never been tried by 41.1%, 59.6% and 72.2%, respectively.
      Fears of addiction and adverse effects were expressed by 31.8% and 48.3%,
      respectively. CONCLUSIONS: New, and even conventional, therapies are often not
      pursued, despite inadequate pain control. Several issues are discussed, including
      patient barriers to seeking pain management, patient and physician barriers to
      analgesic drug therapy, and appropriate use of and access to multidisciplinary
      pain centres. Failure to implement therapeutic advances in pain management not
      only hinders improvement in patient care, but also may render futile decades of
      research. Widespread professional, patient and public education, as well as
      continued interdisciplinary research on treatment barriers, is essential.

PMID- 12518178
TI  - Looking forward, looking back.

PMID- 12518179
TI  - The tachycardic thief.

PMID- 12518180
TI  - Differential effects of once-daily antihypertensive drugs on blood pressure, left
      ventricular mass and sympathetic activity: Nifedipine-GITS versus felodipine-ER
      versus enalapril.
AB  - BACKGROUND: Recent meta-analyses suggest that once-daily dihydropyridines and
      angiotensin-converting enzyme inhibitors cause similar decreases in left
      ventricular (LV) mass for comparable decreases in blood pressure (BP). However,
      some dihydropyridines, such as felodipine-extended release (ER), still increase
      sympathetic activity and may, therefore, be less effective in decreasing LV mass.
      OBJECTIVES: To evaluate the effects of long term antihypertensive treatment with
      nifedipine-gastrointestinal therapeutic system (GITS) and felodipine-ER compared
      with enalapril on LV mass relative to the extent of BP control (assessed by 24 h
      ambulatory BP monitoring) and sympathetic activity (assessed by plasma
      catecholamine concentrations). PATIENTS AND METHODS: Enalapril was started at 10
      mg/day, felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day, all once
      daily. Doses were increased to 20 mg/day, 10 mg/day or 60 mg/day, respectively,
      if the office BP remained 160/90 mmHg or greater at the end of the dosing
      interval. Evaluable echocardiograms were obtained for 116 patients at the end of
      the study (30 weeks of treatment). RESULTS: On 24 h ambulatory BP monitoring,
      nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing
      interval, whereas felodipine-ER caused a more marked fall in BP during the day,
      and enalapril's effects diminished during the night and had disappeared by the
      morning. Only felodipine-ER significantly increased supine and standing plasma
      noradrenaline by more than 50% similarly after six, 18, and 30 weeks of
      treatment. In BP responders (decrease in systolic BP 10 mmHg or greater),
      enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2,
      whereas felodipine-ER was less effective (decrease by only 6 g/m2, P<0.01 versus
      enalapril). CONCLUSIONS: Once-daily dihydropyridines should not be regarded as
      one homogeneous class and, compared with felodipine-ER, nifedipine-GITS exhibits
      a better profile regarding 24 h BP control, sympathetic activation and regression
      of LV mass.

PMID- 12518181
TI  - New insights into the mechanism of the elevation of plasma brain natriuretic
      polypeptide levels in patients with left ventricular hypertrophy.
AB  - BACKGROUND: Messenger RNA of brain natriuretic polypeptide (BNP) is detected in
      both the atrium and the ventricle in vitro. Clinical usefulness has been shown in
      assessment of BNP level in patients with left ventricular hypertrophy; however,
      few studies have reported the role of the atrium and ventricle separately in the
      secretion of BNP from the hypertrophied heart. OBJECTIVE: To investigate how the
      atrium and ventricle secrete natriuretic peptides by comparing the regional
      concentration of atrial natriuretic polypeptide (ANP) or BNP in the hypertrophied
      heart with clinical parameters. PATIENTS AND METHODS: ANP and BNP were measured
      in blood samples from the aortic root, the anterior interventricular vein (AIV)
      and the coronary sinus in 12 control subjects, 10 subjects with hypertensive
      hypertrophy and eight with non-obstructive hypertrophic cardiomyopathy. The
      difference in concentration between the aortic root and the AIV and that between
      the AIV and the coronary sinus was calculated to estimate ventricular and atrial
      secretion, respectively. RESULTS: Plasma BNP levels correlated significantly with
      left ventricular mass index, pulmonary artery wedge pressure, stroke volume and
      left atrial dimension. Stepwise multiple regression analysis identified BNP from
      the atrium, not the ventricle, as an independent predictor of left ventricular
      mass. CONCLUSIONS: These data suggest that atrium-derived BNP is a significant
      predictor of left ventricular mass index in patients with left ventricular
      hypertrophy. The atrium-derived component contributes significantly to the
      elevation of plasma BNP level, reflecting atrial pressure and volume loading in
      left ventricular hypertrophy without systolic dysfunction.

PMID- 12518182
TI  - Practical considerations for the use of nonsteroidal anti-inflammatory drugs and
      cyclo-oxygenase-2 inhibitors in hypertension and kidney disease.
AB  - BACKGROUND: Selective cyclo-oxygenase (COX)-2 inhibitors (coxibs) produce the
      beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) while sparing
      the COX-1-mediated adverse effects on platelets and the gastrointestinal system.
      However, due to the presence of constitutive COX-2 in the human kidney, coxibs
      have the same potential for adverse renal effects as traditional NSAIDs.
      OBJECTIVE: To provide evidence-based guidelines for the use of traditional NSAIDs
      and coxibs in patients potentially at risk for renal and associated hemodynamic
      blood pressure effects. METHODS: All pertinent peer-reviewed papers were
      retrieved with the usual electronic search tools. RESULTS: Both traditional
      NSAIDs and coxibs compromise the glomerular filtration rate in patients at
      increased risk. If there are differences in the blood pressure-raising potential
      of these drugs, these differences do not appear to be clinically significant.
      CONCLUSIONS: The blood pressure should be monitored for all patients taking
      chronic NSAID or coxib therapy. If a clinically significant (4 to 5 mmHg or more)
      increase in blood pressure is detected, the NSAID or the coxib should be
      discontinued and replaced with acetaminophen, to which codeine might be added. If
      the NSAID or the coxib is considered necessary, the increase in blood pressure
      should be treated. In addition, if the glomerular filtration rate reserve is
      compromised, all patients (including those taking short term therapy) should be
      closely monitored for the early detection of signs and symptoms of renal failure.

PMID- 12518183
TI  - Emerging role of angiotensin II type 1 receptor blockers for the treatment of
      endothelial dysfunction and vascular inflammation.
AB  - BACKGROUND: Angiotensin II type 1 receptor blockers (AT1RBs) share the effect of
      attenuating angiotensin II actions with angiotensin-converting enzyme inhibitors
      (ACEIs) but differ in other respects. Notably, the impact of unopposed
      angiotensin type 2 receptor stimulation and the absence of augmentation of
      bradykinin through inhibition of the kininase pathway may lead to differences
      between the effects of AT1RBs and ACEIs. ACEIs have been shown to improve
      endothelial dysfunction in many clinical settings. OBJECTIVE: To review current
      evidence regarding the effects of AT1RBs on endothelial dysfunction in patients.
      METHODS: MEDLINE and Current Contents searches, augmented by careful analyses of
      the bibliographies in the identified papers, were used to identify studies
      assessing the effects of chronic, oral use of AT1RBs on endothelial function and
      related inflammatory markers in patients. Animal studies and human studies using
      single doses or intravenous infusions were excluded. RESULTS: Clinical studies
      are available pertaining to the elderly and patients with coronary artery
      disease, hypertension and diabetes. The effect on endothelial dysfunction induced
      by postprandial lipemia has also been assessed. In general, AT1RBs improve
      vasomotor endothelial dysfunction and some inflammatory markers, but a few
      studies comparing ACEIs directly with AT1RBs suggest that AT1RBs may be inferior.
      AT1RB activity on endothelial dysfunction in patients with type I diabetes has
      not been shown. CONCLUSIONS: AT1RBs are an important addition to the therapy of
      endothelial dysfunction and vascular inflammation in patients. Further research
      is necessary to determine which AT1RBs and which dosing regimens are optimal.

PMID- 12518184
TI  - Combination therapy as first-line treatment of arterial hypertension.
AB  - Mild to moderate hypertension still remains poorly controlled. This relates to
      multiple factors including low antihypertensive efficacy of single drug
      therapies, reluctance of primary care physicians to modify or titrate initially
      chosen therapy to obtain target blood pressure and poor compliance with
      medication. Evidence discussed in the present paper points to superior control of
      blood pressure by combinations of low doses of two drugs compared with
      monotherapy in regular doses. This superior effectiveness of combined therapy
      relates to a better antihypertensive efficacy and higher response rates in the
      low range of doses as the result of complementary mechanisms of antihypertensive
      effects. It is associated with better tolerance as the result of a lower rate of
      side effects in the low range of dosing, improved compliance from better
      tolerance and simple drug regimen, and lower cost. Increased use of fixed, low
      dose combination therapies can be expected to result in better control of
      arterial hypertension in the population. Given the evidence for superior
      antihypertensive efficacy and better tolerability, and the absence of harm from
      fixed, low dose drug combinations per se, this alternative deserves more
      consideration in the guidelines of major hypertension organizations.

PMID- 12518186
TI  - Tachyarrhythmia-induced cardiomyopathy.

PMID- 12518185
TI  - Angiotensin receptors in the cardiovascular system.
AB  - The angiotensin II receptors mediate the effects of the renin-angiotensin system,
      which has an important role in cardiovascular (patho)physiology. Four types of
      angiotensin receptors are known, of which the type 1 (AT1) and the type 2 (AT2)
      receptors are the most important. Stimulation of the AT1 receptor leads to a
      cascade of signalling pathways in several cell types, which finally leads to
      processes such as vasoconstriction, inflammation and proliferation. These
      processes are of great importance in various cardiovascular diseases, including
      hypertension, atherosclerosis and ventricular hypertrophy. The AT2 receptor is
      expressed mainly in the fetal stage. In adults, the AT2 receptor is minimally
      expressed under normal circumstances. Its role in the adult cardiovascular system
      is not well established, but its effects seem to oppose those of the AT1
      receptor. This overview discusses the pathophysiological role of the angiotensin
      II receptors in various cardiovascular diseases with the emphasis on the signal
      transduction of the AT1 and the AT2 receptors.

PMID- 12518188
TI  - Principles of blood transfusion in sickle cell anemia.
AB  - Sickle cell anemia (SCA) is one of the commonly inherited hemoglobinopathies in
      the Kingdom of Saudi Arabia. It is characterized by periods of remissions and
      exacerbations called crises as well as certain pathological phenomenon such as
      acute chest syndrome, priapism, hepatopathy, and cerebrovascular stroke. Blood
      transfusion (BT) as therapy and prophylaxis in SCA, although was advocated as
      early as the 1940's, there are still debates regarding its benefits and risks.
      This is a review of the value of BT in patients with SCA with emphasis on the
      risks and benefits as well as guidelines towards safe BT.

PMID- 12518189
TI  - Travel epidemiology. WHO perspective.
AB  - International travel is undertaken by large, and ever increasing numbers of
      people for professional, social, recreational and humanitarian purposes, and this
      upward trend looks set to continue. Travelers are exposed to a variety of health
      risks of the unfamiliar environment of the visited area. The risk of exposure is
      determined by destination, duration of the visit, purpose of the visit, behavior
      of the traveler and underlying physical and biological status of the traveler.
      However, most risks can be minimized by suitable precautions taken before, during
      and after travel. Travelers can themselves, also, easily introduce any infectious
      agents they may harbor to the visited area. Many infectious diseases have been
      introduced in many parts of the world through travel and trade. Travel has been
      identified as a prime factor in the global spread of infectious diseases. In a
      world of rapid air travel, no country is safe from infectious diseases. An
      outbreak in one country can easily and rapidly be transmitted across long
      distances to affect other countries through travel and trade. The World Health
      Organization devotes great attention to prevention and control of global spread
      of infectious diseases and minimizing the negative effect of international travel
      on health. The main strategies of the World Health Organization for minimizing
      the negative effects of expanding travel on global health security include
      developing the necessary strategies, rules and regulations; strengthening global
      communicable diseases surveillance and response; dissemination of related
      information throughout the world and strengthening national capacity for
      communicable diseases surveillance and response.

PMID- 12518190
TI  - Pregnancy outcome in women with sickle cell trait.
AB  - OBJECTIVE: The aim of the study is to assess the pregnancy outcome among Omani
      women with sickle cell trait (SCT), and to compare it with a control group of
      Omani women with normal hemoglobin. METHODS: Relevant data of both groups was
      obtained from labor room records, patient files and computerized records at the
      Nizwa Hospital, Dakhliya Region, Nizwa, Oman from January 1999 to July 2000.
      Available data was analyzed. RESULTS: Three thousand, five hundred and one
      pregnant Omani women were included in this study, 319 had SCT (9.1%), the average
      age was 27 years in both groups, and 51% were primigravida. There was an increase
      in the incidence of anemia in the SCT women. The incidence of abortion and
      neonatal death in previous pregnancies was significantly increased among SCT
      women. CONCLUSION: Pregnant women with SCT need special care and attention during
      pregnancy, labor, puerperium and surgery. They should be identified early to
      prevent complications such as anemia, infection and fetal wastage.

PMID- 12518192
TI  - Sentinel node in management of malignant melanoma.
AB  - OBJECTIVE: One of the most important prognostic features of malignant melanoma is
      the involvement of regional lymph nodes. The aim of this study is to identify the
      sentinel lymph node which is the first node to be involved by metastases from
      malignant melanoma and then decide which patients can benefit from lymph node
      dissection and which will only need clinical follow-up. METHODS: Forty-four
      patients were included in this study from October 2000 to November 2001. The
      study was carried out at the St. Bartholomew's and Royal Hospital, London, United
      Kingdom. We undertook a pilot study of patients with malignant melanoma involving
      the outline technique. A consent form for all patients was taken. The only
      criteria for inclusion in this study was the Berslow thickness of the tumor which
      had to be over 2 mm. There were 18 females and 26 males, mean age of 57 years.
      The primary tumor site varied: upper limbs 14, lower limbs 10, trunk 18, and head
      and neck 2. RESULTS: Excision of one to 3 sentinel nodes (mean 1.4) was
      performed. The number of sentinel nodes was removed: one in 24 patients, 2 in 12,
      3 in 6, and 4 in 2 patients. In 8/44 patients metastatic disease was detected in
      the sentinel node. Three patients had therapeutic lymph node dissection. There
      was no major complication. Four patients with one positive node each (evidence of
      micrometastases) have gone for lymph node dissection; one of them had one further
      positive node. CONCLUSION: Sentinel lymph node biopsy is increasingly used to
      stage melanoma in order to avoid lymph node dissection in patients who clinically
      have no lymph node involvement. Sentinel lymph node biopsy is a valuable
      technique for melanoma staging; however, impact on overall survival requires
      longer follow-up.

PMID- 12518191
TI  - Intravesical immunotherapy for superficial bladder cancer.
AB  - OBJECTIVE: To compare and evaluate the efficacy and tolerance of intravesical
      instillation of Bacillus Calmette-Guerin (BCG) and interferon alpha-2b
      immunotherapy for superficial transitional cell carcinoma (TCC) of the urinary
      bladder. METHODS: Thirty-five patients with superficial TCC of the urinary
      bladder, primary and recurrent tumors, stage Ta, T1, and grade 1 and 2, were
      prospectively enrolled for intravesical immunotherapy at the Armed Forces
      Hospital, Riyadh, Kingdom of Saudi Arabia between January 1992 and December 2000.
      The treatment regimes used were either 120 mg of BCG weekly for 6 weeks followed
      by a 2nd 6 week course given only on first tumor recurrence, or 50 million i.u.
      of interferon alpha-2b weekly for 3 months, bi-weekly for the next 3 months and
      monthly for 6 months. Twenty-two patients received BCG and 13 received interferon
      alpha-2b. Adequate blood counts, renal and hepatic function profiles, and
      informed consent were required. Cystoscopy was repeated every 3 months for the
      first 2 years, then 6 monthly for another 2 years and then yearly. RESULTS: The
      follow-up period ranged from 9-96 months (median 31.33 months). Twenty patients
      attended the follow-up and were evaluable in the BCG group and 13 in the
      interferon alpha-2b group. In the BCG versus interferon alpha-2b group, the rates
      of complete response were 80% and 41.6%, partial response were 5% and 33.3%, and
      progression were 15% and 8.3%. Mild side effects occurred in 5 patients and all
      of them completed their treatments. There was only one cancer related death in
      each group after 6 and 7 years of starting the treatment. CONCLUSION: Bacillus
      Calmette-Guerin was confirmed as a more effective intravesical immunotherapy for
      superficial TCC of the urinary bladder as compared to interferon alpha-2b. Both
      agents' treatments are well tolerated.

PMID- 12518193
TI  - A comparative analysis of uterine rupture in 2 decades.
AB  - OBJECTIVE: To compare the changing trends of uterine rupture in 2 decades along
      with the maternal and fetal outcome in scarred and unscarred uterus. METHODS: The
      risk factors of the uterine ruptures, which occurred in the Ministry of Health
      Hospitals in Bahrain in 2 decades, were analyzed. The maternal and the fetal
      outcome was compared between the 2 decades (1981-2000) and between the scarred
      and unscarred uterus. RESULTS: The rise of uterine rupture in the 2nd decade (50)
      as compared with the first decade (25) was parallel to the increasing rate of
      cesarean section (CS). Instrumental deliveries and augmentation of labor were the
      main significant risk factors in the first decade while induction of labor was in
      the later decade. There was a significant decrease of maternal morbidity in the
      2nd decade inspite of the increasing rate of uterine rupture. There was no
      maternal death; however, there were 11 perinatal deaths in the first group
      compared to 14 in the 2nd group. The maternal morbidity and perinatal mortality
      was significantly higher in the uterine ruptures of the intact uterus as compared
      to those with scarred uterus. CONCLUSION: Inspite of the high incidence rate of
      the uterine rupture in the later decade, the morbidity of the mother and the
      fetus show no increase. The increase in the incidence of the uterine rupture is
      connected to the increasing rate of CS. The rupture of the intact uterus is more
      catastrophic as compared to the scarred uterus.

PMID- 12518194
TI  - Repeat intracytoplasmic sperm injection. Clinical perspective.
AB  - OBJECTIVE: To report the results of repeat intracytoplasmic sperm injection
      (ICSI) after complete failure of fertilization with initial ICSI. METHODS: The
      medical records of the couples undergoing repeat ICSI at the Human Reproductive
      Biology Unit, Soliman Fakeeh Hospital, Jeddah, Kingdom of Saudi Arabia, after
      complete failure of fertilization by initial ICSI between December 1994 and
      December 2000 were retrospectively examined. RESULTS: Seven hundred and eighty
      two oocytes from 146 women failed to fertilize by initial ICSI. The main
      indications for the procedure were severe oligoasthenoteratozoospermia or
      azoospermia. Fresh sperms were used in 136 cases, of which 98 (72%) were
      ejaculated, 33 (24.3%) were obtained by testicular sperm extraction, and 5 (3.7%)
      by testicular sperm aspiration. Of the remaining 10: 3 were from cryopreserved
      semen samples and 7 were from cryopreserved testicular biopsies. The age of the
      women (mean standard deviation) was 31 16.2 years. The duration of infertility
      was 10.5 9.4 years. A total of 151 (19.3%) oocytes were fertilized after repeat
      ICSI. The number of cleaved embryos was 125 (15.9%); of which 2 (1.6%) were grade
      5, 47 (37.6%) were grade 4, 65 (52%) were grade 3, and 11 (8.8%) were grade 2. A
      total of 122 embryos were transferred to 71 women. This resulted in one pregnancy
      and the birth of a healthy full term baby. CONCLUSION: In cases of complete
      failure of fertilization with initial ICSI, fertilization and pregnancy can
      follow repeat ICSI. Further clinical and cytogenetic studies in this area are
      necessary.

PMID- 12518195
TI  - The significance of autosomal C-band size polymorphism in male infertility.
AB  - OBJECTIVE: The aim of this study is to assess the possible role of autosomal C
      band size polymorphism in male infertility. METHODS: Two-hundred male patients
      with clinical diagnosis of infertility and 100 normal controls were included in
      the present investigation. All patients were assessed by Urologist Consultant at
      the Department of Pathology and Forensic Medicine, Kufa University, Kufa, Iraq,
      during a 2-year-period, October 1999 to October 2001. C-band evaluation was based
      on both quantitative and qualitative methods. Blood culture, chromosome
      harvesting, and C-band technique were carried out according to standard methods.
      RESULTS: 1. C-band quantitative study indicates a significant increase in the C-
      band size of chromosomes 9 and 16 among infertile groups as compared to normal
      fertile group (p<0.01). 2. C-band qualitative study indicates a significant
      increase in the C-band size (level 3) of chromosome number one among the
      infertile group as compared to normal fertile group (p<0.01). CONCLUSION: The
      present findings require further extensive study to shed light on the possible
      correlation between C-band polymorphism and male infertility.

PMID- 12518196
TI  - Deletion mutations in the dystrophin gene of Saudi patients with Duchenne and
      Becker muscular dystrophy.
AB  - OBJECTIVE: The deletion in the dystrophin gene has been reported for many ethnic
      groups, but until now the mutations in this gene have not been thoroughly
      investigated in Saudi patients with Duchenne muscular dystrophy (DMD) and Becker
      muscular dystrophy (BMD). We examined the deletion pattern in the dystrophin gene
      of the Saudi patients applying multiplex-polymerase chain reaction (PCR). The aim
      of this study is to describe the outcome of our initial effort to identify
      mutations in the dystrophin gene in a representative group of Saudi patients with
      DMD and BMD. METHODS: Genomic deoxyribose nucleic acid was isolated from 41
      patients with DMD and BMD (27 patients confirmed by muscle biopsy and 14 patients
      with clinical suspicion), 3 patients with limb girdle muscular dystrophy, 12 male
      relatives of the patients, and 5 healthy Saudi volunteers. A total of 25 exons
      around the deletion prone regions (hot spots) of the dystrophin gene were
      amplified. The study was carried out at the King Fahad National Guard Hospital,
      Riyadh, Kingdom of Saudi Arabia between 2000 and 2002. RESULTS: The deletion of
      one or more exons was found in 21 of 27 DMD and BMD patients confirmed by muscle
      biopsy. The deletion in the gene was detected in 5 of 14 patients with DMD
      diagnosis, but not confirmed by dystrophin staining of muscle biopsy. No deletion
      in the dystrophin gene was detected in control Saudi volunteers, the limb girdle
      dystrophy patients, and the relatives of patients, as expected. CONCLUSION: The
      present study suggests that intragenic dystrophin gene deletions occur with the
      same frequency in Saudi patients compared with other ethnic groups. The PCR-based
      deletion analysis provides a reasonable first step in the diagnostic care of
      Saudi patients who may be afflicted with DMD and BMD.

PMID- 12518198
TI  - Striae distensae-like lesions. A cause of scarring alopecia among children.
AB  - OBJECTIVE: Although alopecia areata is a common problem among children, many
      misdiagnoses for this condition can happen. The aim of this study was to
      demonstrate the striae distensae as lesions that cause scarring alopecia with a
      great resemblance to alopecia areata. METHODS: A total of 36 children with
      provisional diagnosis of alopecia areata of the scalp were assessed clinically in
      the Department of Dermatology and Venereology, Baghdad Teaching Hospital,
      Baghdad, Iraq, between June 1998 to June 2001. Their age ranged from 3 12 years
      and the mean + standard deviation (SD) was 7.30 + 2.59 years with equal sex
      ratio. RESULTS: All patients provided for this study had a history of patchy hair
      loss of few months duration. Their parents denied any history of obvious trauma
      and many modalities of treatment had been tried without benefit. The clinical
      examination revealed single or multiple (1-6) (mean + SD 2.41 + 1.22) complete
      linear hair loss patches resembling atrophic scar that was similar to striae
      distensae. The histopathological examination showed atrophy of the epidermis,
      full replacement of the dermis by collagen bundles, and complete loss of
      appendages. CONCLUSION: This is a new entity, which seems to be common among
      children and often confused with untreated cases of alopecia areata. This
      condition should be added to the differential diagnosis of patchy hair loss in
      children and the parents should be reassured of the cause of hair loss and no
      treatment therapy needed.

PMID- 12518197
TI  - Spinal brace in tuberculosis of spine.
AB  - OBJECTIVE: To present our experience in the management of 22 patients with
      thoracolumbar spine tuberculosis (TB) using a chemotherapy regimen and locally
      custom-made spinal brace. METHODS: Twenty-two patients with thoracolumbar spine
      TB had been treated conservatively by chemotherapy and locally custom-made spinal
      brace and followed for 36-48 months from June 1996 to June 2000 in the Department
      of Orthopedics and Trauma, Algamhoria Teaching Hospital, Aden, Republic of Yemen.
      In 14 cases, 2 vertebrae were involved, whereas in 8 cases involvement was only
      of one vertebra. All had persistent back pain: 2 had neurological deficit,
      Frankel grade A and B (9%), and 12 (54%) had gibbus deformity. RESULTS: At the
      end of the observation period, all patients had no pain (based on the adjective
      rating scale). Fourteen thoracic and 3 psoas abscesses resolved by 18 months.
      Four cases (18%) had deterioration of the angle of kyphosis. Five cases (22.5%)
      had progressive vertebral loss. Twelve cases (84%) had bony fusion at 36 months.
      CONCLUSION: Chemotherapy regimen and locally custom-made spinal brace is not
      costly, needs neither admission nor surgical intervention that demands skills and
      experience and can be recommended for uncomplicated thoracolumbar spinal TB.

PMID- 12518199
TI  - Immunoglobulin G subclass distribution of bullous pemphigoid autoantibodies and
      complement fixation studies.
AB  - OBJECTIVE: The purpose of this study was to examine the immunoglobulin G (IgG)
      subclass distribution of tissue bound and circulating antibasement membrane zone
      antibodies in bullous pemphigoid. In addition, the complement fixing capability
      of circulating IgG subclasses was also investigated. METHODS: Seventeen skin
      biopsies and 25 serum samples obtained from 25 cases of bullous pemphigoid were
      analyzed by direct and indirect immunofluorescence using mice anti-human IgG
      subclasses monoclonal antibodies. Indirect complement immunofluorescence was used
      to measure the avidity with which antibodies activate the complement. The study
      was carried out between 1992 and 1996 at the King Fahd Hospital of the
      University, Al Khobar, Kingdom of Saudi Arabia and the Western Infirmary
      Immunopathology Laboratory, Glasgow, Scotland. RESULTS: Immunoglobulin G1
      deposits were detected in 10 of 17, IgG2 in one, IgG3 in 3 and IgG4 in 15
      biopsies. Immunoglobulin G1 circulating antibodies were observed in 14, IgG2 in
      0, IgG3 in 4 and IgG4 in 24 serum samples. Complement fixing antibodies were
      detected in 15 sera, 4 of which contained only IgG4 subclass. CONCLUSION: The
      predominance of IgG4 subclass observed in this study is similar to previously
      reported results. Complement fixation capability studies revealed non-complement
      fixing sera and the results were not compatible with the complement binding
      characteristics of IgG subclasses. This suggests that other mechanisms, which do
      not involve the complement, may participate in blister formation in bullous
      pemphigoid.

PMID- 12518200
TI  - Efficacy of Daflon in the treatment of hemorrhoids.
AB  - OBJECTIVE: To demonstrate the value of Daflon in the management of hemorrhoidal
      symptoms in Saudi patients attending the Surgical clinic. METHODS: This is a
      prospective clinical study of 105 consecutive patients suffering from
      hemorrhoidal problems including thrombosed piles. Detailed history and
      proctoscopic examination to determine position, size, and degree of hemorrhoids
      was conducted in all patients attending the Surgical Clinic at Dammam Central
      Hospital, Dammam, Kingdom of Saudi Arabia (KSA). The study was conducted over a 6
      months period (December 2000 to May 2001). All were started on Daflon; 2 tablets
      twice daily for 4 weeks and were followed up weekly during the study period and
      proctoscopic examination was conducted at each consultation. RESULTS: The mean
      age was 35 (range 19-70) years. The majority (77%) suffered congested
      hemorrhoidal disease and only 8% had thrombosed piles. Previous surgery for piles
      was noted in 11%. Concomitant medical diseases were present in 10%. The degrees
      of piles were first degree (23 patients), 2nd degree (73), 3rd degree (9) and 4th
      degree (0). There was a statistically significant (p<0.001) improvement in pain,
      heaviness, bleeding, pruritus, and mucosal discharge from baseline to last visit.
      There was also a significant (p<0.001) improvement on the proctoscopic
      appearance. Five patients failed to improve on Daflon; therefore, they underwent
      surgery. The side effects of Daflon (mainly gastrointestinal symptoms) were
      encountered in 5 patients but did not force interruption of the medication.
      CONCLUSION: Daflon is a very safe and effective drug in the treatment of all
      hemorrhoidal symptoms in the population of Eastern KSA.

PMID- 12518201
TI  - Perianal sinuses in neonates and infants.
AB  - OBJECTIVE: The aim of this study is to evaluate the etiology of perianal abscess
      or discharges in neonates and infants and some of them are perianal sinuses with
      blind inner end without connection to the anal canal, and some of these cases
      have a different histological pattern. Complete surgical excision and primary
      closure of their wounds can cure these patients. METHODS: Between January 1988
      and December 2000, (81) neonates and infants (aged 2 weeks to 2 years) with
      perianal sinuses, fistula-in-ano abscess dealt in the Al-Zahrawi and Al-Khansa
      Teaching Hospitals, Mosul, Iraq, were studied. Fifty-one patients displayed an
      onset of symptoms during their first year of age, all cases had a gentle probing
      and proctoscopy under general anesthesia, and the discharge from abscess from the
      patients were sent for culture. Thirty patients with proper sinuses had excision
      of the sinus and primary closure; children with fistulae underwent fistulectomy;
      perianal abscesses drained. All the excised specimens were examined
      histopathologically. RESULTS: All children, except 3, were boys. Out of the 81
      cases studied, 30 patients (37%) proved to have proper sinuses with blind inner
      end. Eight of these showed a different histological pattern, and in 2 cases, the
      histopathology was that of rectal duplication, the microbiology of the discharge
      from the proper sinuses was showing a predominance of non-gut derived organisms.
      All patients cured by excision of the sinuses and primary closure. CONCLUSION:
      Fistulae are the most common perianal discharging lesions in neonates and
      infants, blind sinuses are another cause in a considerable number. We propose a
      diagnostic strategy and treatment for those children presenting with discharging
      perianal lesions; for anticipation of these sinuses 3 points need to be
      considered before attempting surgery. 1) Blind sinus tract on gentle probing. 2)
      Normal anal and rectal mucosa on proctoscopy. 3) High bacterial yield of non-gut
      derived organisms on culture of the pus or discharge. Their treatment is by
      simple excision (coring) and primary closure; this method will shorten the
      healing and recovery time.

PMID- 12518203
TI  - Availability of resources of diabetic care in primary health care settings in
      Aseer region, Saudi Arabia.
AB  - OBJECTIVE: The objective of this study is to evaluate the availability of
      resources of diabetes care in primary health care settings in Aseer region,
      Southwest, Kingdom of Saudi Arabia. METHODS: This study was conducted during
      September 2001 by distributing a questionnaire to all technical directors of
      primary health care centers (PHCCs) in Aseer region. The questionnaire, designed
      by the authors, contained 6 sections that dealt with the necessary structures of
      diabetic care in the region in addition to the data base of PHCC such as served
      population, distance from the hospital, and total working physicians and nurses
      at the PHCC. The data from the questionnaire was entered and analyzed using
      Statistical Package for Social Sciences. RESULTS: Two hundred and forty-two PHCC
      technical directors responded to the questionnaire. Total served population by
      PHCC was 970,306 individuals. Total working physicians were 391 and nurses were
      902. Diabetics represented 2.7% of the total served population. More than 90% of
      PHCCs have diabetic files, registers, appointment system and protocol for
      diagnosis and treatment of diabetes. Oral hypoglycemic agents were always
      available at 55% of PHCCs while metformin was not available at 52% of PHCCs.
      Diabetic identification cards were available in 80.4% of PHCCs while the health
      education means were less available, except for health education programs was
      available at 97.5% of PHCCs. At least, 40% of PHCCs were provided financially or
      by different means of health education through community health committees.
      CONCLUSION: This study revealed that resource items for diabetic care are
      inadequate in particular drugs and laboratory facilities. Establishment of a
      diabetes committee in Aseer region is a priority in order to manage such
      shortages and to plan, supervise and coordinate the diabetic care in the region.

PMID- 12518202
TI  - Evaluation of direct light microscopy for rapid detection of microorganisms in
      blood cultures.
AB  - OBJECTIVE: The aim of this study was to evaluate the use of direct light
      microscopy (x 40 objective) of unstained uncentrifuged blood-broth mixtures for
      rapid detection of microorganisms in blood cultures. METHODS: Two thousand two
      hundred and ninety-four blood cultures were investigated in this study. Blood
      cultures were processed in the Clinical Microbiology Laboratory, Queen Alia
      General Hospital, Amman, Jordan from January to December 2001. We compared the
      results of direct light microscopy and subcultures in 3 stages: macroscopically
      positive blood culture bottles, macroscopically negative blood culture bottles
      after 9-17 hours, and macroscopically negative blood culture bottles after 7 days
      of incubation. RESULTS: The total positive blood cultures was 434 (18.9%). Three
      hundred and fifty three (81.3%) were positive by macroscopic examination and
      direct light microscopy and grew viable organisms, 34 were macroscopically
      negative blood cultures that grew viable organisms after 9-17 hours of incubation
      in which 32 (94.1%) were positive by direct light microscopy and 47
      macroscopically negative blood cultures that grew viable organisms after 7 days
      of incubation in which 45 (95.7%) were positive by direct light microscopy.
      CONCLUSION: The direct light microscopy methodology proved to be simple, rapid,
      cost effective, accurate and sensitive technique for the early detection of
      bacteremia.

PMID- 12518204
TI  - Clinical presentation of adult celiac disease in Western Saudi Arabia.
AB  - OBJECTIVE: To study the clinical presentation of adult celiac disease. METHODS: A
      retrospective study of adult patients who were diagnosed with celiac disease
      based on findings of small intestinal biopsy, response to gluten free diet and
      exclusion of other causes of malabsorption or vitamin deficiency over a period of
      5 years from 1998-2002. The study was carried out at the King Abdul-Aziz
      University Hospital, Jeddah, Kingdom of Saudi Arabia. RESULTS: Sixteen patients
      were diagnosed with celiac disease. Osteomalacia and iron deficiency anemia were
      common clinical presentations. Diarrhea, malabsorption associated with growth
      failure was observed in 3 patients with a mean age of 14.5 years. Celiac disease
      associated with other autoimmune diseases was reported in 6 patients. Insulin
      dependent diabetes mellitus in 3 patients, Hashimoto's hypothyroidism in 2
      patients and dermatitis herpetiformis in one patient. No malignancy was observed
      during the follow-up of our patients. There was a good clinical and biochemical
      response to gluten free diet in 12 cases. CONCLUSION: Osteomalacia and iron
      deficiency anemia were common clinical presentations of celiac disease. Hence,
      the presence of either one of them in a female patient should raise the
      possibility of celiac disease.

PMID- 12518205
TI  - Screening for congenital hypothyroidism in North-West region of Saudi Arabia.
AB  - OBJECTIVE: The aim of this study is to demonstrate the prevalence of congenital
      hypothyroidism (CH) in Madina Al-Munawara region, Kingdom of Saudi Arabia (KSA)
      and to compare the results with other reported studies. METHODS: All deliveries
      conducted at the Ministry of Health Hospitals, Health Centers and Private
      Hospitals in Madina Al-Munawara region, KSA during the period from 1989 to 1999
      were included in this study. Cord blood samples for thyroid stimulating hormone
      (TSH) measurement was used for screening. RESULTS: Out of 200,040 deliveries
      193,613 infants were screened for CH during the study period. Forty-six infants
      had hypothyroidism with an overall prevalence of 1:4208 live births. Thirty-three
      (72%) of the diagnosed infants were Saudi and 13 (28%) were not Saudi. The male
      to female ratio was 1:3. The mean age at the start of treatment was 9 days.
      CONCLUSION: The screening program based on the initial measurement of TSH in cord
      blood is detected by nearly 97% of the total infants born in Madina region over
      10 years. The overall prevalence of CH was 1:4208 lower than other local studies.
      Mental retardation can be prevented by neonatal screening program; however,
      Neonatologists and Pediatricians should remain vigilant in searching for signs
      and symptoms of CH.

PMID- 12518206
TI  - Successful separation of thoracopagus conjoined twins.
AB  - The first successful separation of thoracopagus conjoined twins in Eastern Saudi
      Arabia with 2-year follow up is presented. Physical examination and radiographic
      studies revealed a conjunction that extended from midsternum to a common
      umbilicus. The shared internal organs included liver and pericardium. The
      separation was performed at the age of 4 months. The resulting chest wall defects
      in both twins were covered by dacron-reinforced silastic prosthesis. The
      abdominal wall defect was primarily closed in the "left twin," and covered with a
      dacron reinforced silastic sheet in the "right". Primary skin closure was
      achieved in both, following extensive mobilization of the skin. The
      musculoskeletal deformities in the neck, chest and vertebral column showed marked
      improvement 20 months after separation.

PMID- 12518207
TI  - Goldenhar syndrome and hereditary tyrosinemia type 1.
AB  - We report a case of Goldenhar syndrome and hereditary tyrosinemia type 1 (HTT1),
      to our knowledge an association not previously described. This case further
      increases the diversity of observations and clinical descriptions of patients
      with this complex syndrome. We discuss pathogenetic aspects, and demonstrate
      further evidence of the effectiveness of 2-(2-nitro-4-trifluoromethyl benzoyl)
      1,3-cyclohexanedione in the treatment of HTT1.

PMID- 12518208
TI  - Traumatic fat embolism syndrome.
AB  - Traumatic fat embolism syndrome occurs most often following fractures of long
      bones sustained in road traffic accidents and is a common cause of medical
      consultation from the orthopedic surgery department. The sub-clinical
      presentation is subtle and expresses itself by the presence of hypoxemia, while
      the full clinical syndrome compromises respiratory insufficiency, an altered
      consciousness and a characteristic petechial rash. Recognition is simple once the
      patient is viewed in the context of his or her clinical setting. Diagnosis is
      aided further by the presence of hematological and biochemical abnormalities
      including anemia, thrombocytopenia, an elevated erythrocyte sedimentation rate
      and fat macroglobulinemia. Imaging by chest radiograph, computed tomography or
      magnetic resonance of the brain is used to confirm the extent of the respective
      organ involvement and to exclude alternative pathologies. The release of free
      fatty acids into the circulation and their subsequent effects is the key
      pathological event. Treatment is based on supportive care and high-dose
      corticosteroid therapy. We report a patient with traumatic fat embolism syndrome
      who developed the syndromes classical symptoms and signs following fracture of
      the long bones of his left lower leg. Admission to an intensive care unit,
      mechanical ventilatory support with positive end-expiratory pressure and
      corticosteroid therapy lead to his improvement and allowed eventual open
      reduction and internal fixation and discharge of our patient. Modern therapy
      offers a relatively good prognosis for patients with traumatic fat embolism
      syndrome; the optimal dose and timing of corticosteroid therapy in prophylaxis
      and treatment however, remain the subject of intense debate.

PMID- 12518209
TI  - Single coronary artery arising from the left sinus of valsalva.
AB  - A single coronary artery is a rare congenital anomaly of the coronary arteries
      where only one coronary artery arises from the aortic trunk by a single coronary
      ostium, supplying the entire heart. We report a case of a 57-year-old woman with
      atypical chest pain, in whom coronary angiography showed a L-I subtype single
      coronary artery (arising from a single ostium in the left sinus of valsalva)
      without associated cardiovascular disease. The clinical significance and subtype
      of the single coronary artery are discussed.

PMID- 12518210
TI  - Diabetes mellitus and cystic fibrosis in 2 Saudi siblings.
AB  - Diabetes mellitus and cystic fibrosis (CF) have been reported before in the
      literature, but they have never been reported in the same patient in the Middle
      East. We present the first reported case of insulin dependent diabetes mellitus
      (IDDM) and CF in 2 siblings of the same family. Both siblings were diagnosed
      early in life with IDDM, and their diabetes was well controlled on insulin.
      Cystic fibrosis was diagnosed in the first case one year after IDDM was diagnosed
      due to history of chronic cough and in the 2nd case by family screening. Both had
      severe failure to thrive, recurrent chest infections and gastro-esophageal
      reflux. With treatment both showed clinical improvement, but continued to have
      moderate lung disease radiologically and by pulmonary function test.

PMID- 12518211
TI  - Peyronie's disease. Who is at risk?

PMID- 12518212
TI  - Hypoglycemia in diabetics during Hajj.

PMID- 12518213
TI  - Cryptorchidism.

PMID- 12518214
TI  - Paradoxical response to anti tuberculous drugs.

PMID- 12518215
TI  - Ovarian diseases at King Abdul-Aziz University Hospital.

PMID- 12518216
TI  - The pattern of peripheral blood chromosomal abnormalities in Northern Jordan.

PMID- 12518217
TI  - Medical research in developing countries still in Cinderella status.

PMID- 12518218
TI  - Extra pulmonary tuberculosis in Saudi Arabia.

PMID- 12518219
TI  - Allergic bronchopulmonary aspergillosis: a view from India.

PMID- 12518220
TI  - [Fatty acid synthase: specific target for cancer therapy].
AB  - Fatty acids, the products of fatty acid synthesis, are essential components and
      forms of energy for cancer growth. Compared to normal human tissues, many common
      human cancers express elevated levels of fatty acid synthase (FAS), the important
      enzyme responsible for the synthesis of fatty acid, suggesting FAS can be a
      specific target for cancer therapy.

PMID- 12518222
TI  - Expression, purification and in vitro N-myristoylation of human Src N-terminal
      region.
AB  - The DNA fragment encoding N-terminal region of human c-Src was amplified from
      Caco-2 cell total RNA by RT-PCR and cloned into vector pMFHT to obtain His-tag
      fusion expression plasmid pMF-SrcHT, which was based on T7 expression system. The
      fusion protein SrcHT was highly expressed in E.coli BL21(DE3) harboring the pMF
      SrcHT and purified from bacterial lysate by Ni-IDA affinity chromatography. The
      assays using [(3)H]-labeled substrate demonstrate that the purified fusion
      protein SrcHT can be effectively N-myristoylated by recombinant human myristoyl
      CoA: protein N-myristoyltransferase (NMT) in vitro. This work is a basis for
      further biochemical studies and development of new anti-cancer chemotherapeutic
      drugs based on specific inhibition of N-myristoylation of human Src.

PMID- 12518221
TI  - Preparation of an anti-Cdx-2 antibody for analysis of different species Cdx-2
      binding to acat2 promoter.
AB  - The homeodomain protein, Cdx-2, as transcription factor has been implicated in
      the transcriptional regulation of genes expressed in small intestine and the
      process of tumorgenesis. In current work, a conserved mouse Cdx-2 domain (mCdx
      2D) coded by its cDNA fragment, which was amplified and cloned into the
      expression vector pGEX-4T1, was expressed as a fusion protein with GST (GST-mCd x
      2D) and purified by one step of affinity chromatography. A polyclonal antibody
      against Cdx-2 was raised by using the recombinant fusion protein GST-mCdx-2D as
      antigen and was fractionated from the rabbit anti-serum. Western blot and EMSA
      (electrophoretic mobility shift assay) demonstrate that the natural and denatured
      Cdx-2s from different species (mouse and human) can be detected by the prepared
      anti-Cdx-2 antibody. Most notably, we found that the Cdx-2 in human intestine
      cell line Caco-2 is expressed in a differentiation-dependent manner and can
      efficiently bind to the mouse and human acat2 (acyl-coenzyme A: cholesterol
      acyltransferase 2) promoter regions, suggesting that the transcriptional factor
      Cdx-2 may play a role in regulating the acat2 expression in the intestinal cells.

PMID- 12518223
TI  - Promoter activities in the baculovirus envelope glycoprotein gp64 gene.
AB  - Baculovirus GP64 envelope glycoprotein is a specific major component of the
      envelope of the budded virus and is involved in virus entry into the host cells
      by endocytosis. For promoter activity analysis in the baculovirus gp64 gene, two
      DNA fragments containing 437 and 439 bp upstream of 5' ends of the BmNPV and
      AcMNPV gp64 ORF were amplified by polymerase chain reaction and cloned,
      respectively. The sequence analysis indicated that two gp64 genes have both early
      (CAGT) and late (A/GTAAG) transcriptional start sites. By use of the plasmids
      with a reporter luciferase gene (Luc) driven by gp64 promoter to transfect insect
      cells, transient expression assay showed that pBmgp64Luc had high expression
      levels in permissive Bm-N cells and very low levels in non-permissive Sf-21
      cells, while pAcgp64Luc had relatively high expression levels both in permissive
      Sf-21 cells and in non-permissive Bm-N cells. Furthermore, the transcription of
      both gp64 promoters appeared to be transactivated by 2.4-4 times in corresponding
      permissive cells by corresponding viral factors, separately. By inserting BmNPV
      homologous region-3 (hr3) into the downstream of luciferase reporter gene driven
      by gp64 promoter, it enhanced transcription from both gp64 promoters by 13 - 22
      times in Bm-N cells and over 7000 - 14,000 times in Sf-21 cells, respectively. In
      the presence of BmNPV hr3, correspondingly, the viral factors transactivated the
      transcriptional activity from two promoters by about 73 - 78 times in
      corresponding permissive cells. It suggested that BmNPV hr3 plays an important
      role in co-activation with viral factors onto the gp64 promoter besides the
      functions of viral DNA origin and enhancer.

PMID- 12518224
TI  - Expression of human papillomavirus type 6 L1 and L2 isolated in China and self
      assembly of virus-like particles by the products.
AB  - To study variations of genome late region of human papillomavirus type 6 (HPV-6)
      isolated in China and assembling capabilities of the encoded capsid proteins, HPV
      6 L1 and L2 sequences were cloned and used for expression in Bac-to-Bac
      baculovirus expression systems (Gibco BRL). Based upon L1 and L2 overlapping
      sequence two sequences (GenBank accession number AY015006, AY015008) of HPV-6
      late region (2869 bp long) were assembled and classified into HPV-6b by
      phylogenetic analysis. Compared with prototype sequence, nine point mutations
      were found, including four missense mutations. L1, instead of L2, could self
      assemble into virus-like particles (VLPs) in Sf9 nucleus. VLPs self-assembled by
      L1 alone (L1-VLPs) and by L1 plus L2 (L1+L2-VLPs) were purified and further
      characterized. Both types of VLPs were spherical particles with a diameter of
      approximately 50 nm. L1+L2 VLPs comprising L1 and L2 in the molar ratio of about
      4:1 possessed the HPV-6 L1 VLP surface and conformational epitopes. In co
      expression assay with a series of MOI combination of L1 and L2 recombinant
      baculoviruses (total MOI=10), existence of L2 of certain level enhanced L1
      production by 0.8 fold and VLP production by 3 - 4 folds under experimental
      conditions. In conclusion, variation rate of HPV-6 genome late region is less
      than 0.28% and the substitutions A to G at position 7081 and G to A at 7099 may
      represent region characteristics. The cloned HPV-6 L1 and L2 sequences can be
      expressed efficiently in Sf9 cells, and the expressed products (L1 or L1+L2) can
      self-assemble into VLPs that resemble naturally occurring virions.

PMID- 12518225
TI  - A soft docking algorithm for predicting the structures of protein-protein
      complexes.
AB  - An efficient soft docking algorithm is described to predict the mode of binding
      between two proteins based on the three-dimensional structures of molecules. The
      molecular model used in this work was grounded on the "simplified protein" model
      used in Janin's docking algorithm. The side chain flexibility of the amino acid
      residues Arg, Lys, Asp, Glu and Met at the protein surface was considered through
      softening the molecular surface. A double filtering technique was used to
      eliminate most of the unlike binding modes. The energy minimization was performed
      on the retained structures, and then these structures were evaluated with the
      scoring function which included electrostatic, desolvation and van der Waals
      energy terms. The 26 complexes were used to test this docking algorithm and good
      results were obtained. The native-like conformations of all the complexes were
      all found, of which 20 were ranked in the top 10.

PMID- 12518226
TI  - [G-protein-coupled muscarinic acetylcholine receptor activation up-regulates Bcl
      2 and phospho-bad via Ras-ERK-1/2 signaling pathway].
AB  - Activation of G-protein coupled muscarinic acetylcholine receptors and MAPKs/ERK
      1/2 has been found to inhibit neural cell apoptosis and promote neural cell
      survival. Bcl-2 protein family also plays an important role in regulating neural
      cell apoptosis and survival. However, signaling pathways coupling muscarinic
      receptors to Bcl-2 family remains to be elucidated. In the present study, it was
      found that carbachol not only activated MEK/ERK-1/2 signaling pathways, but also
      increased the expression levels of Bcl-2 and phospho-Bad proteins in human
      neuroblastoma SH-SY5Y cells. These effects were blocked by a muscarinic receptor
      antagonist (atropine) and a MEK inhibitor(PD98059)   and were significantly
      attenuated by a Src family kinases inhibitor(PP1) and a PKC inhibitor
      (bisindolymaleimide-I), but were not influenced by a G(i/o)-uncoupling reagent
      (pertussin toxin) and a PI-3 kinase inhibitor (wortmannin). Furthermore,
      carbachol also stimulated Bcl-2 promoter-driven luciferase gene expression in
      transfected SH-SY5Y cells. Co-transfection of Ras or Raf dominant negative
      mutants with the pBcl-2-Luc plasmid abolished carbachol  s effects. These data
      suggested that muscarinic acetylcholine receptors regulated the expression of Bcl
      2 protein family by Ras-ERK-1/2 signaling pathway involving the pertussin toxin
      insensitive G-proteins, PKC and Src.

PMID- 12518227
TI  - [Simultaneous expression of CS3 colonization factor antigen and LT-B/ST fusion
      enterotoxin antigen of enterotoxigenic Escherichia coli by attenuated Shigella
      flexneri 2a].
AB  - Enterotoxigenic Escherichia coli (ETEC) causes watery dehydrating diarrhea in
      infants in developing countries, and is the most common cause of travelers  
      diarrhea. It has been known that the colonazition factor antigens (CFAs) and
      enterotoxins are important virulence factors of ETEC, and these two kinds of
      proteins should be included in any effective vaccine against ETEC. In this study,
      a host-plasmid lethal balancing system was constructed based on asd gene in an
      avirulent strain of S.flexneri to express CS3 antigens and the fusion LT-B/ST
      enterotoxins of Escherichia coli. Both of these antigens were expressed steadily
      in the S. flexneri vector without any antibiotic markers. Antibodies against CS3,
      LT, ST and LPS of Shigella were detected in sera of mice that were immunized with
      recombinant bacteria either oragastrically (o.g.) or intranasally (i.n.). SIgA
      against CS3 and enterotoxins were detected simultaneously in feces of mice. This
      work is helpful for constructing multivalent recombinant vaccine for prevention
      of bacterial diarrhea.

PMID- 12518228
TI  - [Effect of expression of gut-enriched Kruppel-like factor on esophageal squamous
      cancer cells].
AB  - Gut-enriched Kruppel-like factor (GKLF) is a newly identified eukaryotic zinc
      finger protein expressed extensively in the gastrointestinal tract, and its
      expression is associated with growth arrest. Previous work showed that GKLF
      expression was down-regulated in esophageal squamous cancer. In the present work,
      the effects of sense and antisense expression of GKLF on the esophageal squamous
      cancer cell line EC9706 were observed to get more knowledge of the role of down
      regulation of GKLF in the initiation and/or progression of esophageal cancer.
      Antisense transfection of GKLF gene in EC9706 led to decreased expression of GKLF
      in the cells, and these cells showed increased cell growth rate, indicating that
      down-regulation of the GKLF gene might contribute to cellular hyperproliferation.
      Both increased and decreased expression of GKLF in EC9706 by sense and antisense
      GKLF expression also led to the decreased adhesion of cells, suggesting a role of
      GKLF in the metastasis of esophageal squamous cancer. The results demonstrate
      that down-regulation of GKLF expression in esophageal squamous cancer causes the
      cancer cells to become hyperproliferative and less adhesive, and suggest that
      decreased expression of GKLF may contribute to the malignant phenotype of
      esophageal squamous cancer.

PMID- 12518229
TI  - [NMR study on solution configuration of mHCN1 pore peptide].
AB  - Spin systems for amino acid residues in mHCN1 pore region peptide have been
      identified through analysis of 2D NMR spectra. The sequence-specific assignment
      of spin systems was obtained by NOEs correlation in WET-NOESY spectra, and the
      complete assignment of proton resonances for backbone and side chain has been
      achieved. CNS software was used to calculate the structure of mHCN1 19 aa
      peptide. The results show that an alpha-helix from residue 10 to residue 13 is
      formed within the pore region. The results of NMR study on mHCN1 pore peptide
      provide the basis for further understanding the mechanism of ion selectivity of
      channels.

PMID- 12518230
TI  - [Ionizing radiation-regulated killing of human hepatoma cells by liposome
      mediated CDglyTK gene delivery].
AB  - EGR-1 gene promoter and CDglyTK gene were used to construct the pcDNA3-EGR
      CDglyTK recombinant vector, in which CDglyTK gene expression was under the
      control of EGR-1 gene promoter. Cationic liposome LipofectAMINE was used to
      transfect plasmids into human hepatoma 7402 cell line. Subsequently, the
      transfected cells were treated with different doses of gamma-ray. Northern blot
      and Western blot showed that ionizing radiation can induce CDglyTK gene
      expression drived by EGR-1 promoter,in a dose-dependant manner. There was no
      ionizing radiation-inducible effect in pcDNA3-CMV-CDglyTK control group. Ionizing
      radiation also markedly enhanced the sensitivity of tumor cells transfected with
      pcDNA3-EGR-CDglyTK to prodrugs (GCV/5-FC) in tumor cell killing. The data
      indicated that EGR-1 promoter was inducible by ionizing radiation, whereas the
      CMV promoter was not. There was a synergetic effect between GCV and 5-FC. The
      cytotoxic effect of the suicide gene-ionizing radiation combination was stronger
      than suicide gene alone or ionizing radiation alone.

PMID- 12518231
TI  - [Combined recombinant DNA vaccine results in significant protection against
      Mycobacterium tuberculosis].
AB  - Three proteins secreted from Mycobacterium tuberculosis, Ag85B, ESAT-6 and MPT63
      were selected as antigens for making combined DNA vaccine by immunizing mice. The
      immune response induced by the vaccine and its protective efficacy were studied.
      It was demonstrated that when mice were immunized with the combined DNA vaccine,
      the titer of antibody for Ag85B in serum increased to more than 10(5), but the
      titers of ESAT-6 and MPT63 specific antibodies were undetectable. After the final
      immunization, the level of gamma specific for Ag85B, ESAT-6 and MPT63 reached
      (17.0+/-7.0) u/ml, (6.0+/-0.8) u/ml and (11.9+/-8.0) u/ml, respectively. Mice,
      that were inoculated with the empty eukaryotic expression vector pJW4303 DNA,
      produced negligible amounts of antigen-specific INF-gamma. The combined DNA
      vaccine resulted also in significantly reduced amount of bacteria in the lungs of
      experimental mice. Microphotographs showed clearly that these lungs were better
      protected against Mycobacterium tuberculosis challenge than control mice. The
      combined DNA vaccine reported in this work shed new lights on the prophylactic
      protection against tuberculosis.

PMID- 12518232
TI  - [The binding sites of estrogen receptor for miyabenol C and kobophenol A].
AB  - To examine the binding sites of miyabenol C (Miy C) and kobophenol A ( Kob A)
      with estrogen receptor (ER), computer modeling was applied to determine 3D
      structure of Miy C and Kob A. Molecular docking of the components to ER was
      carried out to find the binding sites between them. PCR mutagenesis was used to
      change the structure of ER cDNA. After the mutated sites were confirmed by DNA
      sequencing, report gene assay was used to study the effects of Miy C and Kob A on
      the trans-activating ability of ER. Results indicated that the effect of Miy C on
      the trans-activating ability of mutant 1 of ER [M1ER (ER M(517)AG(521)D)] was
      decreased, and Kob A had no stimulating effects on the trans-activating ability
      of M1ER. Miy C and Kob A had no stimulating effects on the trans-activating
      ability of mutant 2 of ER [M2ER (ER E(353)GR(394)G)]. Therefore, the ER sites for
      Miy C and Kob A may be located at Glu(353), Arg(394), Met(517) and Gly(521).

PMID- 12518233
TI  - Inhibition of sodium channels in rat dorsal root ganglion neurons by Hainantoxin
      IV, a novel spider toxin.
AB  - The effects of Hainantoxin-IV (HNTX-IV), a neurotoxic peptide isolated from the
      venom of the Chinese bird spider Seleconosmia hainana, on the adult rat dorsal
      root ganglion (DRG) neurons were investigated. Using the whole-cell patch-clamp
      technique HNTX-IV inhibited mammal neural TTX-sensitive (TTX-S) sodium currents
      evidently but the toxin failed to affect TTX-resistant (TTX-R) ones. The
      inhibition of HNTX-IV is dose-dependent with the IC(50) value of 44.6 nmol/L. The
      toxin didn't affect the activation and inactivation kinetics of sodium currents,
      but it caused a 10.1 mV hyperpolarizing shift in the voltage midpoint of steady
      state sodium channel inactivation on DRG neurons. The results indicated that HNTX
      IV, a novel spider toxin, maybe alternate voltage-gated sodium channels through a
      mechanism distinct from other spider toxins such as delta-ACTXs, mu-agatoxins I
      VI which targeted the receptor site 3 to slow the inactivation kinetics of sodium
      currents.

PMID- 12518234
TI  - [Involvement of PHO80 and PHO85 genes in Saccharomyces cerevisiae ion tolerance].
AB  - PHO85 is a versatile gene in Saccharomyces cerevisiae, which is involved in
      metabolism of inorganic phosphate and usage of carbon source, accumulation of
      glycogen, regulation of protein stability and cell cycle control. The viability
      of wild type budding yeast strain YPH499 and its derivative pho85Delta mutant,
      pho80   mutant, and pap1(pcl-7)Delta mutant in different cations were
      investigated and their tolerance to the cations(LC(50)) was measured. The results
      showed that the deletion of PHO85 or PHO80 gene both increased sensibility of
      Sacchromyces cerevisiae to ions K(+), Mg(2+), Zn(2+), Ca(2+) and Mn(2+), while
      the deletion of pap1(pcl-7) gene did not lead to such phenotype. The difference
      between the patterns of relative growth curve of the mutants and wild type strain
      in the above ions also implied that PHO80 was the unique PCLs in complex with
      PHO85 CDK, that were contributed to K(+) and Mg(2+) ion homeostasis control and
      there were some other PCLs besides PHO80 that were involved in Zn(2+), Ca(2+) and
      Mn(2+) tolerance regulation as cyclin of PHO85 CDK. Furthermore, the amount of
      the total cellular calcium of pho85Delta mutant, pho80Delta mutant and YPH499
      indicated that the ability of calcium accumulation of pho85   mutant and
      pho80Delta mutant was impaired.

PMID- 12518235
TI  - [Cloning of ESTs of spermatogenesis-related genes from early stage spermatogenic
      cells of mice using a modified DDRT-PCR method].
AB  - To avoid the shortcomings of radioactive pollution and high rate of false
      positives in DDRT-PCR method, the technique have been modified by replacement of
      radioactive reagents with fluorescent reagents followed by confirming the results
      using reverse RNA dot blot. The modified DDRT-PCR method was used in this study
      to clone spermatogenesis-related genes from early stage spermatogenic cells of
      mice. Primitive spermatogonia were isolated from 6-day-old mice and type B
      spermatogonia from 9-day-old mice. The purity of isolated cells was over 90%.
      Total RNA was extracted from the cells, fluorescent differential display
      technique was performed to screen the differentially expressed genes. Differences
      in expression of the screened fragments were identified by reverse RNA dot blot.
      16 ESTs were selected for sequencing. The analysis results in GenBank/Blast
      database revealed that 7 of them were novel ESTs, and they were then registered
      in GenBank. All of them expressed stronger in B spermatogonia than in primitive
      spermatogonia. 3 of them were chosen to further identify their expression
      patterns by semi-quantitative RT-PCR. Compared with traditional differential
      display technique, the modified method used in this study can avoid radioactive
      pollution and eliminate false positive results. The present study suggests that
      the gene activation or up-regulation in B spermatogonia may be related to some
      specific process in the following steps of spermatogenesis.

PMID- 12518236
TI  - [Sequence analysis of RNA3 of Rice stripe virus isolates found in China: evidence
      for reassortment in Tenuivirus].
AB  - The RNA3 segments of four isolates of Rice stripe virus (RSV), isolated from
      endemic sites at Panjin (PJ), Liaoning Province, Kunming (KM) and Yiliang (YL),
      Yunnan Province, as well as from outbreak sites at Hongze (HZ), Jiangsu Province,
      were determined. RNA3 of these four isolates were 2480 bp, 2509 bp, 2489 bp and
      2497 bp in length, respectively. Compared with RNA3 of T and M isolates from
      Japan and Y isolate from Yunnan Province of China, that had been previously
      reported, these seven isolates could be divided into two groups. KM and YL
      isolates formed group one, and PJ, HZ, Y, T and M isolates belonged to another
      group. The two groups shared 97%-98% and 93%-94% sequence homology in viral RNA3
      (vRNA3) and viral complementary RNA3 (vcRNA3) at the nucleotide levels,
      respectively, and there was no significant difference between the two groups at
      the amino acid levels. In the first group, Y isolate was significantly different
      from HZ,PJ and two Japan isolates in their RNA4 segment. These results show that
      there were two subgroups in RSV natural population related with geographical
      location, and reassorment may be the main factor leading to different segments of
      Y isolate belonging to different subgroups. The results may provide another
      evidence for reassortment variation in Tenuivirus.

PMID- 12518237
TI  - Inhibitory effects of bucillamine on increased blood-retinal barrier permeability
      in streptozotocin-induced diabetic rats.
AB  - PURPOSE: To investigate the effect of bucillamine for prevention of increasing
      blood-retinal barrier (BRB) permeability in streptozotocin (STZ)-induced diabetic
      rats. METHODS: The groups included control and STZ-induced diabetic rats treated
      with or without bucillamine. Six months after intervention, the concentrations of
      reduced and oxidative glutathione (GSH and GSSG) in the retina were measured
      biochemically. In addition, vitreous fluorescein, which leaks from the vessels
      after intravenous injection of fluorescein sodium, was measured to evaluate BRB
      permeability. To evaluate the scavenging ability against the reactive oxygen
      species (ROS) in vitro, the second-order rate constant for the reaction of
      bucillamine with ROS was estimated from the kinetics based on the rate constant
      for the reaction of ROS. RESULTS: The BRB permeability was significantly higher
      (p = 0.01) in diabetic rats not treated with bucillamine, and bucillamine
      inhibited the BRB permeability. The GSH concentration and the GSH/GSSG ratio in
      the retinas decreased in diabetic rats not treated with bucillamine; bucillamine
      inhibited the decrease of the GSH concentrations. The ROS scavenging activity of
      bucillamine was similar with that of GSH. CONCLUSIONS: In diabetic retinas,
      oxidative stress might increase, which may be one of the causes of BRB breakdown.
      The antioxidant effects of bucillamine might take part in inhibition of increased
      permeability of the BRB in diabetes.

PMID- 12518238
TI  - Blood and lens lipid peroxidation and antioxidant status in normal individuals,
      senile and diabetic cataractous patients.
AB  - PURPOSE: Oxidative mechanisms are believed to play an important role in the
      pathogenesis of cataract, the most important cause of visual impairment at
      advanced age. To determine the body's antioxidant status as well as its lipid
      peroxidation levels, both blood and lens parameters were evaluated. METHODS: This
      study was performed on the blood samples and lenses obtained from 46 patients
      diagnosed as having cataract and 20 control subjects. The control group was
      composed of 10 women and 10 men who do not smoke. Control subjects without any
      lens opacity or vacuoles when observed with a slit lamp were recruited on the
      same exclusion criteria as far as disease and treatment were concerned. No
      antioxidant medicines were used. They were all healthy individuals without any
      systemic diseases. Superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase
      (G6PD), glutathione reductase (GSSG-Red) activities in red blood cell (RBC)
      lysates as well as whole blood glutathione (GSH) and plasma thiobarbituric acid
      reactive substances (TBARS), the indicator of lipid peroxidation concentrations,
      were determined quantitatively both in the blood samples and the lenses of the
      patients with senile and diabetic cataracts. RESULTS: Whole blood GSH values, and
      erythrocyte SOD activities were significantly lower in the cataractous patients
      than those in the control group. The values in the diabetic cataractous group
      were also less than those in the senile cataractous group. Significantly
      decreased erythrocyte GSSG-Red and G6PD activities were detected in the diabetic
      cataractous group. Plasma TBARS values were higher both in the senile and
      diabetic groups when compared to those in the control group. Significantly
      decreased values were observed for GSSG-Red activities and TBARS values in the
      lenses of the senile cataractous patients in comparison with those in the
      diabetic cataractous patients. The lens GSH values were found to be higher in the
      senile cataractous group than the values obtained in the diabetic cataractous
      group. CONCLUSIONS: A strong correlation was found between lens GSH and lens
      TBARS concentrations in the diabetic group. This emphasized the vital role of GSH
      as an antioxidant in the lens over the other antioxidant parameters, e.g.,
      enzymes, and the oxidative stress is at the highest level in lens.

PMID- 12518239
TI  - Angiogenesis in pterygium: morphometric and immunohistochemical study.
AB  - OBJECTIVE: To evaluate the role of angiogenesis in the pathogenesis of pterygium
      by comparing the expression of von-Willebrand factor (vWF) and vascular
      endothelial growth factor (VEGF) in pterygium, and in normal superior bulbar
      conjunctiva. METHODS: 23 human samples from pterygium and the superior bulbar
      conjunctiva were stained using rabbit anti-vWF and anti-VEGF antibodies. The
      density of vWF and VEGF positive vessels, VEGF staining intensity and the number
      of VEGF positive stromal, epithelial and vascular endothelial cells were
      evaluated. RESULTS: Pterygium specimens had higher average vWF and VEGF positive
      microvascular counts per high power field (P = 0.0012), higher average VEGF
      staining intensity scores in epithelial, stromal and endothelial cells (p <
      0.0001) and higher VEGF positive cell counts (P < 0.0001) than normal conjuctiva.
      CONCLUSIONS: Over-expression of VEGF in pterygium tissue, together with the
      abundance of vWF-stained new vessels, may support previous suggestions that
      angiogenesis may play a role in the formation of pterygium.

PMID- 12518240
TI  - Adenosine relaxation in small retinal arterioles requires functional Na-K pumps
      and K(ATP) channels.
AB  - PURPOSE: To study the effect of Na-K pump and K(ATP) channel inhibition on the
      diameter and the adenosine-induced vasodilation of small retinal arterioles.
      METHODS: Thirty isolated porcine arterioles with a diameter of approximately 70
      microm were mounted in a double-barrelled pipette system placed in an organ bath,
      and diameter changes were studied under isobaric no-flow conditions. After an
      equilibration period, the arterioles were incubated with the Na-K pump inhibitors
      ouabain and low K(+) medium or the K(ATP) channel inhibitor glibenclamide, and
      spontaneous diameter changes were studied. Subsequently, the arterioles were
      precontracted and the adenosine concentration response curve was measured with
      and without the presence of inhibitors. RESULTS: Inhibition of the Na-K pump
      elicited a significant decrease in the spontaneous diameter of the vessels (P =
      0.047), whereas no change in the spontaneous diameter was induced by inhibition
      of the K(ATP) channels (P = 0.754). Inhibition of the Na-K pump with ouabain or
      with low K(+) medium, as well as inhibition of the K(ATP) channels with
      glibenclamide, both diminished the adenosine induced vasodilation (P = 0.003, P =
      0.01, and P = 0.003, respectively). CONCLUSION: The adenosine-induced
      vasodilation of small retinal arterioles involves the K(ATP) channels and the Na
      K pump. Changes in the metabolism of adenosine as well as the activity of the
      K(ATP) channels or the Na-K pump can be expected to influence the retinal blood
      flow.

PMID- 12518241
TI  - Gap junctional communication in the human corneal endothelium and epithelium.
AB  - PURPOSE: Gap junctional communication in the epithelium and endothelium of human
      corneas was studied. The influence of corneal storage on endothelial gap
      junctions was also examined. METHODS: Donor human corneal cells were injected
      with carboxyfluorescein while surrounding cells were monitored for traces of
      fluorescence. Dye-spread coefficients were measured in corneal endothelial cells.
      Western blot and immunohistochemical analysis of the endothelium and epithelium
      was employed to determine if connexin 43 was present. RESULTS: Dye coupling
      occurs in both the epithelium and endothelium of the human cornea. Epithelial dye
      coupling was extensive in the basal layers but less apparent in the superficial
      layers. Endothelial dye coupling was similar to that reported for rabbit corneas.
      Western blot and immunohistochemical analyses demonstrated the presence of
      connexin 43 in both cell types. CONCLUSION: Gap junctional communication occurs
      in the endothelium and epithelium of human corneas, and both cell types express
      connexin 43. These results are similar to previous rabbit studies, thereby
      strengthening the use of the rabbit cornea as a gap junction model.

PMID- 12518242
TI  - A portable instrument for measuring macular pigment with central fixation.
AB  - PURPOSE: To evaluate the reliability and validity of a portable instrument for
      measuring macular pigment optical density. METHODS: The instrument is small, uses
      light emitting diodes as light sources and the principles of heterochromatic
      flicker photometry of comparing foveal and extra-foveal minimum flicker matches.
      It uses central fixation for the extra-foveal matches, which subjects found
      easier than eccentric fixation. Subjects with healthy eyes used the instrument to
      measure their pigment density in a number of eye clinics. RESULTS: The mean
      pigment density in 124 eyes in 124 individuals was 0.41 +/- 0.16 (mean +/- SD),
      there was no significant change with age but the density was less in females,
      those with light irides, smokers, subjects on diets low in precursor carotenoids
      and in those exposed to several hours of daylight every day or who used sun beds.
      CONCLUSIONS: The portable instrument gave valid and reliable data that confirmed
      published values for macular pigment. It was convenient to use in the clinic and
      has potential as a screening tool.

PMID- 12518244
TI  - The role of different phospholipids on tear break-up time using a model eye.
AB  - PURPOSE: The effect of different phospholipids in stabilising the tear film was
      investigated to determine if particular polar head groups gave greater stability
      than others. METHODS: Purified phosphatidylcholine (PC), lysophosphatidylcholine
      (LPC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG),
      phosphatidylserine (PS) and cardiolipin (CL) were used. These were applied to a
      model eye loaded with an artificial tear fluid and the tear break-up time (TBUT)
      was measured. Three variants of the artificial tear fluid were utilised: buffered
      saline alone; one with proteins and mucins; and one containing proteins, mucins
      and lipids. RESULTS: TBUT was improved by the presence of phospholipids. In
      particular, the best performance was with PI applied to artificial tear fluid
      containing proteins mucins and lipids. Use of buffered saline as the artificial
      tear fluid gave very short break-up times. CONCLUSION: Increase in tear film
      stability by phospholipids is probably not due to the charge carried by the polar
      head group, but more likely due to the charge distribution, and the presence of
      hydroxyl groups in the head group also tends to increase stability, possibly
      through specific interactions with proteins and mucins in the subphase.

PMID- 12518243
TI  - Lipid hydroperoxide induced corneal neovascularization in hyperglycemic rabbits.
AB  - PURPOSE: To compare the effect of hyperglycemia on corneal neovascularization
      (NV) induced by linoleic acid hydroperoxide (LHP) in a rabbit model. METHODS:
      Male New Zealand rabbits received 80 mg/kg alloxan i.v. and subsequently
      developed hyperglycemia. Four weeks later, 10 microl of LHP (40 mM) was injected
      into corneal stroma 5 mm from the superior limbus with a 30 gauge needle. Vessel
      growth area from the limbal vasculature was measured over a period of 2 weeks and
      was correlated with plasma levels of insulin, HbA(1c), and corneal vascular
      endothelial growth factor (VEGF). RESULTS: Two days after alloxan, blood glucose
      was increased from 97 +/- 4 mg/dl in the untreated control group to 413 +/- 3
      mg/dl. At 24 and 72 hours after LHP injection, VEGF in cornea of hyperglycemic
      rabbits was elevated 2 to 4 times above that of normoglycemic rabbits. At 14 days
      after LHP injection, the normoglycemic rabbits vessel growth area measured 2.42
      +/- 0.31 mm(2), but in the hyperglycemic group, vessel growth area was
      significantly increased to 7.96 +/- 2.26 mm(2) (p < 0.05). At the end of the
      experimental period, HbA(1c) was elevated from 3.9 +/- 0.8 % to 8.4 +/- 0.6 % and
      insulin was decreased from 440 +/- 123.9 pg/ml to 24 +/- 11.0 pg/ml. CONCLUSIONS:
      These data suggest that hyperglycemia may sensitize corneal and vascular
      endothelial cells, perhaps by glucose derived radicals, which enhance production
      of additional LHP through endogenous propagation reactions, and raise in turn the
      concentration of VEGF levels to induce an enhanced, sustained NV response.

PMID- 12518245
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. CONCLUSION: 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- 12518246
TI  - Adrenocortical peptides: autocrine or paracrine regulators for the steroid
      hormone secretion or the cell proliferation?
AB  - There is accumulating evidence that indicates the production and secretion of
      some peptides by adrenal cortex and adrenocortical tumors. These peptides include
      adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP), endothelin-1,
      cerebellin, urotensin-II etc., and appear to be involved in the regulation of
      steroid hormone secretion and the proliferation of adrenocortical cells as
      autocrine and/or paracrine factors. It is noteworthy that expression of
      adrenomedullin is induced by hypoxia and inflammatory cytokines in various cells,
      raising the possibility that the adrenocortical production of adrenomedullin (and
      probably PAMP) may be increased in some inflammatory and/or ischemic conditions,
      and these two peptides may modulate the states of inflammatory and/or ischemic
      disorders. In addition to adrenomedullin and PAMP, adrenal cortex and/or some
      adrenocortical tumors express endothelin-1, cerebellin, urotensin-II, etc. The
      adrenocortical peptides may form a novel autocrine or paracrine regulatory system
      for the steroid hormone secretion and the cell proliferation in the adrenal
      cortex, and involve in the pathophysiology of inflammatory, ischemic or
      neoplastic diseases of the adrenal cortex

PMID- 12518247
TI  - The value of low dose (1 microg) ACTH stimulation test in the investigation of
      non-classic adrenal hyperplasia due to 11beta-hydroxylase deficiency.
AB  - Non-classic congenital adrenal hyperplasia (NCAH) is a rare cause of hirsutism
      and it results from a defect in the biosynthetic pathway of cortisol and/or
      aldosterone. 250 microg ACTH test (SDT) is used in the diagnosis of this disease.
      Our aim was to investigate the responses of 11-deoxycortisol to 1microg ACTH
      (LDT) test in women with NCAH due to 11-beta hydroxylase (11- beta OH) deficiency
      and to compare them with the values obtained after SDT in the patients and in the
      control subjects. Eleven patients with NCAH due to 11- beta OH deficiency and 15
      control subjects were involved in the study. The main complaint of the patients
      with NCAH was hirsutism and the diagnosis was made if the adrenal 11
      deoxycortisol response to SDT exceed threefold the 95th percentile of controls.
      ACTH stimulation tests were carried out consecutively by using 250 microg and 1
      microg intravenous ACTH as a bolus injection after an overnight fast, and blood
      samples were drawn at 0,30 and 60 min. Peak cortisol, 17-hydroxyprogesterone (17
      OHP) and DHEAS responses were similar in LDT and SDT while 11-deoxycortisol
      responses to LDT (15.7 +/- 1.8 nmol/L) were significantly (p < 0.005) lower than
      the results obtained after SDT (76.3 +/- 21.4 nmol/L) in women with 11- beta OH
      deficiency. Peak cortisol and 17-OHP responses to LDT in patients and control
      subjects were similar. Peak 11-deoxycortisol responses to LDT were significantly
      (p < 0.05) higher in NCAH patients (15.7 +/- 1.8 nmol/L) than in the control
      subjects (6.5 +/- 0.8 nmol/L). However, in LDT, all patients had peak 11
      deoxycortisol level lower than threefold the 95th percentile (25.8 nmol/L) of
      controls. This study represents the first demonstration that LDT gives similar
      cortisol but not 11-deoxycortisol responses to SDT in patients with 11- beta OH
      deficiency. This study also showed that LDT can not replace SDT in every clinical
      situation.

PMID- 12518248
TI  - In vitro and in vivo angiogenesis in PC12 pheochromocytoma cells is mediated by
      vascular endothelial growth factor.
AB  - Angiogenesis, the formation of new blood vessels from existing vascular
      endothelium, is essential for tumor growth. Vascular endothelial growth factor
      (VEGF) is an endotheliumspecific mitogen and regulator of angiogenesis.
      Angiogenesis has been associated to the malignant phenotype of pheochromocytomas
      and is readily observed in experimental pheochromocytomas. Although VEGF gene
      expression has already been demonstrated in the rat PC12 cell line, the detailed
      mechanisms of action are not known. We have, therefore, studied angiogenesis in
      the rat PC12 pheochromocytoma cell line in vitro and in vivo. VEGF gene
      expression and accumulation of VEGF protein in cytoplasm and conditioned medium
      of PC12 cells was found. Conditioned medium from PC12 cells significantly
      increased proliferation of VEGF-dependent endothelial cells from human umbilical
      veins, and this effect reversed upon addition of a neutralizing anti-VEGF
      antibody. Dexamethasone and nerve growth factor (NGF) increased VEGF mRNA
      expression and accumulation of VEGF protein of PC12 subclones with established
      metastatic activity in vivo. PC12 cells xenotransplanted to nude mice had marked
      VEGF expression and induced host angiogenesis, confirmed by the presence of CD34
      positive endothelial cells in the experimental PC12 tumors. When NGF-primed PC12
      cells were immobilized in Matrigel supplemented with rising concentrations of the
      growth factor and xenotransplanted, increasing NGF resulted in tumors with
      smaller areas of necrosis and increased vital tumor volume. These results suggest
      that VEGF is a mediator of angiogenesis in the PC12 pheochromocytoma cell line,
      and that dexamethasone and NGF affect VEGF expression. Our data further suggest
      that NGF may contribute to angiogenesis in experimental pheochromocytoma.

PMID- 12518249
TI  - Three-year survey of effects of iodized oil injection in schoolchildren with
      iodine deficiency disorders.
AB  - High prevalence of goiter, other IDD such as impaired physical and intellectual
      growth and hearing deficit have been reported previously in Kiga. In order to
      evaluate the effect of iodized oil injection, this study was conducted in
      schoolchildren of Kiga village from 1989 to 1992. One ml of iodized oil solution
      containing 480 mg of iodine was injected into 198 schoolgirls and boys aged 8-14
      years. Serum thyroid hormones, RT 3 U, TSH and thyroglobulin, before and 12, 24
      and 36 months after the intra-muscular injection of iodized oil were measured.
      Assessment of urinary iodine was performed at the same periods by Foss method.
      Prior to the injection, all schoolchildren had goiters larger than grade 1 A (48%
      were grade 3); 3 years after intervention 20% had grades zero and 1 A and 8%
      grade 3 (P < 0.001). Urinary iodine was 11.4 +/- 19.8 before and increased to 113
      +/- 63 and 83 +/- 66 microg/g creatinine 2 and 3 years after intervention. Mean
      serum T 4 was 5.0 +/- 2.1, 10.8 +/- 2.8, 9.8 +/- 2.5 and 9.5 +/- 2.1 microg/dl
      before and 12, 24 and 36 months after the injection, respectively (P < 0.001).
      Mean serum TSH was 20.3 +/- 22.8, 1.2 +/- 1.6, 0.8 +/- 1.2 and 2.2 +/- 0.9 mU/L
      in the same intervals, respectively (P < 0.001). Mean serum thyroglobulin was 132
      +/- 107, 10 +/- 12 and 23 +/- 20 ng/ml before and at 2 and 3 years after
      injection, respectively (P < 0.001). Slight but significant increases in serum
      TSH and thyroglobulin occurred at 3 years after the injection. Findings show
      benefits of iodized oil administration in decreasing goiter size and in resuming
      normal thyroid function up to 3 years after the intervention. An increase in TSH
      and or thyroglobulin could be considered as the first sign of a fall in
      effectiveness of iodized oil injection.

PMID- 12518250
TI  - Regulation of sodium-iodide-symporter gene expression in human thyrocytes
      measured by real-time polymerase chain reaction.
AB  - The sodium-iodide-symporter (NIS) plays a key role in iodination, the first step
      in the biosynthesis of the thyroid hormones, and is thought to be critically
      involved in several thyroid disorders associated with altered iodine up-take. To
      elucidate the pathogenic role of NIS in these diseases a sensitive technique is
      needed to measure human NIS gene expression. We established a real time RT-PCR
      for accurate quantification of hNIS mRNA levels based on fluorescence-labelled
      hybridisation probes in the LightCycler system. Human NIS expression was
      investigated in primary cultures of human thyrocytes. After optimisation of PCR
      conditions less than 10 molecules hNIS were detected with high sensitivity,
      specificity and reproducibility. Under basal conditions NIS expression varied
      from 83 to 593 copies per 10 6 GAPDH molecules. Stimulation of thyrocytes with
      TSH (0.1-10 U/ml) or forskolin (0.1-15 microM) results in a dose- and time
      dependent up-regulation of NIS expression reaching a maximum at 10 mU/ml TSH
      (2211 +/- 761 copies) or 10 microM forskolin (1663 +/- 302 copies) after 24 h. In
      conclusion, we here established a real-time RT-PCR combining the advantages of
      rapid thermocycling and online detection of NIS mRNA amplification. The sensitive
      quantification of human NIS mRNA expression offered by this novel technique may
      improve analysis of hNIS regulation and measurement of NIS mRNA expression in
      small biopsies.

PMID- 12518251
TI  - Role of conventional ultrasound and color Doppler sonography in the diagnosis of
      medullary thyroid carcinoma.
AB  - Early diagnosis of medullary thyroid carcinoma (MTC) can improve long-term
      prognosis. MTC can be detected at an early stage by calcitonin screening in all
      patients with thyroid nodules. This approach, however, is controversial due to
      high costs and a limited specificity of calcitonin. It was the aim of the present
      study to investigate whether ultrasonography may contribute to the diagnosis of
      MTC in patients with thyroid nodules. The study included 19 patients with newly
      diagnosed MTC. Ten patients had sporadic MTC, 7 had multiple endocrine neoplasia
      (MEN) type 2A, and 2 patients had MEN 2B. In all subjects conventional
      ultrasound, and in 14 patients color Doppler sonography were performed before
      primary surgery. For comparison, ultrasound appearance of 139 benign thyroid
      nodules was evaluated. In conventional ultrasound, MTC in 17/19 (89%) patients
      were hypoechoic, contained intranodular calcifications, and had no "halo sign".
      The combination of these criteria were found in only 8/139 (6%) of benign thyroid
      nodules. Intranodular blood flow was found in 11/14 patients with MTC (79%),
      perinodular blood flow in 7/14 MTC (50%). In conclusion, conventional ultrasound
      reveals a combination of hypoechogenicity, intranodular calcifications, and
      absence of "halo sign" in the vast majority of MTC. Since this sonographic
      pattern only rarely occurs in benign thyroid nodules, the results indicate that
      thyroid ultrasound can contribute to the diagnosis of MTC. In addition, the
      findings may have implications for calcitonin screening in nodular thyroid
      disease.

PMID- 12518252
TI  - Non-autoimmune primary hypothyroidism in diabetic and non-diabetic chronic renal
      dysfunction.
AB  - The aim of this study was to investigate the frequency and mechanisms of
      hypothyroidism observed in diabetic patients with advanced diabetic nephropathy,
      including outcomes of management for this condition. A controlled study was
      designed using 32 diabetic and 31 non-diabetic patients not receiving
      hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) who excreted
      mean urinary protein greater than 0.5 g/day examined on three consecutive days
      during admission to our hospital. Thyroid hormones in both serum and urine, anti
      thyroid antibodies, renal function and iodine concentrations in serum were
      measured during admission in all patients included. In particular, in patients
      who showed overt hypothyroidism, further studies including large-needle biopsies
      of the thyroid and iodine-perchlorate discharge tests were performed. All
      patients in the two groups revealed negative antithyroid antibody titers, and the
      mean serum total iodine levels did not significantly differ between the two
      groups. Mean serum FT4 levels significantly decreased, and the TSH level was
      significantly elevated in the diabetic group compared to those in the non
      diabetic group (p < 0.005, p < 0.02, respectively). The frequency of overt
      hypothyroidism in the diabetic group (22%; 7/32) was significantly higher (p <
      0.05) than that in the non-diabetic group (3.2%; 1/31). The daily urinary thyroid
      hormone excretion in both groups did not show any significant correlation with
      serum thyroid hormone levels. Seven patients who revealed overt hypothyroidism in
      the diabetic group showed elevated serum total iodine levels during hypothyroidal
      status, ranging between 177 and 561 microg/l. Also, the iodine-perchlorate
      discharge tests carried out in six of these patients all showed a positive
      discharge. After management based on iodine restriction, normalization of serum
      thyroid hormone levels in accordance with definite decreases in the serum total
      iodine level was achieved, accompanied by a significant weight reduction. In
      conclusion, we found a significantly high prevalence of non-autoimmune primary
      hypothyroidism in patients with advanced diabetic nephropathy compared to those
      with non-diabetic chronic renal dysfunction, which may partly relate to earlier
      development of oedematous status. Clinical and laboratory findings suggest that
      impaired renal handling of iodine resulting in an elevation of serum iodine
      levels, rather than autoimmune mechanism or urinary hormone loss, may play a
      principal role in the development of these conditions, probably through a
      prolongation of the Wolff-Chaikoff effect. The mechanisms by which this
      phenomenon develops more frequently in diabetic than in non-diabetic renal
      dysfunction remain to be elucidated.

PMID- 12518253
TI  - Differences in pharmacokinetics and pharmacodynamics of insulin lispro and aspart
      in healthy volunteers.
AB  - Pharmacokinetic and pharmacodynamic profiles of the rapid-acting insulin
      analogues lispro and aspart were compared in a randomized, double-blind crossover
      study of 20 fasting healthy men following a single subcutaneous injection. Either
      insulin lispro or aspart, 0.05 U/kg-body-weight, was injected subcutaneously and
      followed by determination of 5-h profiles of plasma glucose, serum C-peptide and
      insulin concentrations. Lowest glucose concentrations were observed after 50 min
      in the aspart group (3.2 +/- 0.1 mmol/l versus lispro 3.5 +/- 0.1 mmol/l; p =
      0.026) and after 60 min in the lispro group (3.4 +/- 0.1 mmol/l). For blood
      glucose t min was 59.3 +/- 3.4 min in the aspart and 63.5 +/- 5.3 min in the
      lispro group (ns). After 40 min a lower C-peptide was determined for aspart (225
      +/- 21 pmol/l versus lispro 309 +/- 33 pmol/l; p = 0.031), whereas minimal C
      peptide concentrations were reached in both groups after 105 min (lispro 117 +/-
      21 pmol/l versus aspart 105 +/- 18 pmol/l). The maximal concentration of insulin
      was detected in both groups after 40 min (lispro 20.8 +/- 1.1 mU/l versus aspart
      24.6 +/- 1.3 mU/l; p = 0.032). For insulin t max was 33.0 +/- 2.6 min in the
      aspart versus 33.3 +/- 2.6 min in the lispro group (ns). The present results
      indicate a more rapid absorption of insulin aspart in comparison to insulin
      lispro. Higher insulin concentrations after subcutaneus injection may be
      advantageous in meal-related treatment of diabetes.

PMID- 12518254
TI  - Combined pancreas and kidney transplantation in a lean type 2 diabetic patient.
      Effects on insulin secretion and sensitivity.
AB  - BACKGROUND/AIMS: Pancreas transplantation is an established method of treating
      Type 1 diabetes. It was our aim to test the consequences of pancreas
      transplantation in a Type 2 diabetic patient by determining insulin secretion and
      sensitivity before and after surgery. PATIENTS AND METHODS: A female patient with
      Type 2 diabetes and end-stage nephropathy was treated with combined pancreas and
      kidney transplantation. Before surgery and at 4 weeks, 6 months and 2 years
      afterwards, insulin sensitivity was measured using hyperinsulinemic euglycemic
      clamps and insulin secretion was quantified after oral glucose or intravenous
      glucagon challenges. RESULTS: The patient was insulin resistant before surgery
      (glucose infusion 4.6 mg. kg (-1). min (-1), normal range 6.4 +/- 0.5 mg.kg( -1).
      min (-1). Insulin sensitivity declined further after transplantation (1.4 and 3.0
      mg. kg -1. min -1 after 4 weeks and 6 months, respectively), but improved to 5.4
      mg. kg (-1). min (-1) after 2 years. Insulin secretion was greatly impaired
      before surgery. Insulin and C-peptide responses after oral glucose and
      intravenous glucagon increased into the normal range from 6 months after surgery
      onwards and oral glucose tolerance remained non-diabetic (IGT). CONCLUSIONS:
      Insulin resistance is first aggravated after pancreas transplantation, probably
      due to immunosuppressive treatment including glucocorticoids, but improves on the
      long term. The initially impaired insulin secretion from the transplant may also
      be explained by the action of glucocorticoids or by transient and reversible
      organ damage.

PMID- 12518255
TI  - [Language activation in ischemic stroke and brain tumor: a PET study].
AB  - Disturbance of neurologic function in disorders of the central nervous system is
      expressed as altered activation pattern in functional networks after specific
      tasks, and can be studied by functional imaging modalities, e.g. positron
      emission tomography (PET). Language, a complex brain function is based on the
      interplay of a distributed network in which partial functions are executed in
      various centers and tasks are hierarchically organized according to their
      complexity. The specialization of different centers and the lateralization of
      integrative functions into the dominant (usually left) hemisphere is achieved by
      collateral and transcallosal inhibition of structures of lower order in the
      network. Patients with ischemic stroke often suffer from aphasia; the features
      and the prognosis of this disturbance is determined by the localization and the
      extent of the infarct in the dominant hemisphere. The preservation of the left
      superior temporal gyrus or its functional reintegration, respectively, is of
      utmost importance for the recovery of the deficits and for a satisfactory
      outcome. Reactivation of this region in repeated PET-activation studies were
      related to a favorable outcome, activation of other eloquent regions or of
      contralateral areas were accompanied by some improvements, but never indicated
      recovery of sufficient speech production. Symptoms develop slowly in patients
      with tumors in the left hemisphere, and the functional network can adapt to the
      lesion. In these patients a dislocation of areas activated during language tasks
      was observed, either to ipsilateral regions usually not involved or to
      contralateral homotopic areas. Aphasia was frequent in cases with activation
      shift to the subdominant hemisphere, and the right over left asymmetry in
      activation of the cerebellum was correlated to the severity of language
      impairment. The shift of dominance in activation could be reversed after surgical
      resection of the tumor leading to improved speech performance. The patterns of
      intrahemispheric as well as interhemispheric compensation may be explained by
      reduction of collateral inhibition of specific centers on other structures within
      the network (disinhibition): circumscript and/or slowly developing lesions
      disinhibit surrounding areas leading to increases and to displacements of
      activated centers; large morphological defects reduce the transcallosal
      inhibition leading to the activation of contralateral regions.

PMID- 12518256
TI  - [Cost analysis of intraoperative neurophysiological monitoring (IOM)].
AB  - INTRODUCTION: A number of studies demonstrate that a significant reduction of
      postoperative neurological deficits can be achieved by applying intraoperative
      neurophysiological monitoring (IOM) methods. A cost analysis of IOM is imperative
      considering the strained financial situation in the public health services.
      MATERIAL AND METHODS: The calculation model presented here comprises two cost
      components: material and personnel. The material costs comprise consumer goods
      and depreciation of capital goods. The computation base was 200 IOM cases per
      year. Consumer goods were calculated for each IOM procedure respectively. The
      following constellation served as a basis for calculating personnel costs: (a) a
      medical technician (salary level BAT Vc) for one hour per case; (b) a resident
      (BAT IIa) for the entire duration of the measurement, and (c) a senior resident
      (BAT Ia) only for supervision. RESULTS: An IOM device consisting of an 8-channel
      preamplifier, an electrical and acoustic stimulator and special software costs
      66,467 euros on the average. With an annual depreciation of 20%, the costs are
      13,293 euros per year. This amounts to 66.46 euros per case for the capital
      goods. For reusable materials a sum of 0.75 euro; per case was calculated.
      Disposable materials were calculate for each procedure respectively. Total costs
      of 228.02 euro; per case were,s a sum of 0.75 euros per case was calculated.
      Disposable materials were calculate for each procedure respectively. Total costs
      of 228.02 euros per case were, calculated for surgery on the peripheral nervous
      system. They amount to 196.40 euros per case for spinal interventions and to
      347.63 euros per case for more complex spinal operations. Operations in the
      cerebellopontine angle and brain stem cost 376.63 euros and 397.33 euros per case
      respectively. IOM costs amount to 328.03 euros per case for surgical management
      of an intracranial aneurysm and to 537.15 euros per case for functional
      interventions. Expenses run up to 833.63 euros per case for operations near the
      motor cortex and to 117.65 euros per case for intraoperative speech monitoring.
      DISCUSSION: Costs for inpatient medical rehabilitation have increased
      considerably in recent years. In view of the financial situation, it is necessary
      to reduce postoperative morbidity and the costs it involves. IOM leads to a
      reduction of morbidity. The costs for IOM calculated here justify its routine
      application in view of the legal and socioeconomic consequences of surgery
      related neurological deficits.

PMID- 12518257
TI  - In-vivo measurement of cytochrome using NIRS during acute focal cerebral
      ischaemia and reperfusion in rats.
AB  - OBJECTIVES: Near-infrared spectroscopy (NIRS) based technology allows in-vivo
      monitoring of focal tissue cytochrome aa3 (cytochrome-c-oxidase). The aim of this
      study was to assess early cell alteration during acute focal cerebral ischaemia
      and reperfusion. METHODS: Focal cerebral ischaemia was induced in 12 rats using
      an endovascular occlusion technique of the middle cerebral artery (MCA).
      Occlusion time was 60 minutes followed by reperfusion for another 60 minutes.
      Monitoring of oxygen saturation (SO2) and oxidized cytochrome complex (oxid.
      Cytaa3 ) was performed by NIRS via a parietal burr hole before (baseline), during
      occlusion and reperfusion. Twenty-four hours after MCA occlusion (MCAO)
      infarction was confirmed by TTC staining. RESULTS: In all animals SO2 and oxid.
      Cytaa 3 immediately decreased to zero during occlusion indicating complete
      ischaemia. According to the results of NIRS measurements during reperfusion
      animals were subdivided into two groups. All animals of group A demonstrated
      identical or even higher levels of SO2 and oxid. Cytaa3 compared to baseline. On
      the contrary, both parameters in group B remained at a distinct lower level
      compared to baseline (p < 0.05). Average reperfusion/baseline ratios for SO2 and
      oxid. Cytaa 3 were 0.8 (+/- 0.4) and 0.4 (+/- 0.2), respectively. The results of
      TTC-staining were distributed to the above mentioned two groups as follows: group
      A, only lesions in the basal ganglia or little cortical infarction (n = 8); group
      B, lesions in the basal ganglia and cortical area (n =4). CONCLUSIONS: After 1
      hour MCAO a subgroup of animals with associated cortical infarction was
      identified, whose oxid. Cytaa3 values did not reach baseline values during
      reperfusion indicating early intracellular disturbance.

PMID- 12518258
TI  - Vertebral artery injury after cervical spine trauma: a prospective study.
AB  - OBJECTIVES: Vertebral artery (VA) -injury is rarely symptomatic and can therefore
      easily be overlooked. However, thromboembolic complications may result in
      permanent morbidity or mortality due to brainstem ischemia and infarction. In
      this prospective study a standardized protocol for the diagnosis and management
      of VA-injury following blunt cervical spine trauma with subluxation or fractures
      affecting the transverse foramen was evaluated. METHODS: During a 48 months
      period 31 (12 female, 19 male; mean age 44.2 years) of 119 patients with blunt
      cervical spine trauma were suspicious for VA-injury and subjected to a predefined
      radiological work-up. Selective digital subtraction angiography (DSA) was
      performed at admission in 31 patients. For comparison magnetic resonance
      angiography (MRA) was added within 2 days in 7 patients. RESULTS: The incidence
      of VA injury detected by DSA (n = 5) was 4% in all types of blunt cervical spinal
      injury, 16% in cases suspicious for VA injury, i.e. cases with mono- or bifacet
      dislocation and/or cases with fractures extending into the transverse foramen.
      Unilateral VA-stenosis was found in 4 and VA-occlusion in one patients. In one
      case a VA-stenosis by an intimal flap after transverse foramen fracture was
      detected by DSA but not by MRA. In 2 patients with VA injury headache occurred
      without signs of vertebro-basilar insufficiency. All 5 patients with VA-injury
      were treated with anticoagulation without complications or side effects. 14 of 31
      patients which had DSA/MRA had unstable spine conditions and were treated
      surgically within 4 days after admission. CONCLUSION: The subgroup of patients
      with dislocation or fracture related stenosis of the transverse foramen should
      undergo early angiography for establishment of anticoagulation to prevent
      thromboembolic complications. It appears that the radiological diagnosis of VA
      insufficiency is more sensitive than clinical findings, which rarely indicate VA
      insufficiency. In this series one VA injury was overlooked with MRA.

PMID- 12518259
TI  - Imaging problems and clinical findings in adolescent lumbar disc herniation: a
      retrospective study.
AB  - OBJECTIVES: Disc degeneration probably begins in childhood although low back pain
      and radicular leg pain is not as common a complaint as in adults. However as yet
      no explanation exists for the appearance of advanced degenerative changes seen
      occasionally in patients in their twenties. PATIENTS AND METHODS: We report 12
      adolescents between the ages of 15 and 20 among a total of 1068 cases with
      radiologically demonstrated lumbar disc herniations treated between March 1991
      and March 1996. RESULTS: Most of their findings were in good agreement with
      earlier and more recent reports. The only different findings worth commenting
      upon were the common presence of multiple level disc herniations, and the
      occasional presence of a so called "fractured epiphysial plate". CONCLUSION:
      Depending on magnetic resonance imaging findings coupled with computed
      tomographic images; we suppose that the so called "fractured bone fragments of
      the vertebral epiphysial rim impinging on the spinal canal at multiple levels"
      and "wedges of bone attached to the disc end plate and associated bony defects in
      the margins of the posterior vertebral bodies" reported to be demonstrated on
      computed tomographic (CT) images may in fact be false images. Inappropriately
      angled CT scan slices may cut partly through the epiphysial ring which has
      totally been distracted backwards together with the firmly attached avulsed disc
      annuli, designated as an "epiphysial avulsion"; giving rise to the mistaken
      interpretation as a "fractured epiphysial ring" appearance. Such a mechanism may
      also involve the posterior longitudinal ligament, which is firmly attached to the
      neighboring annuli, accounting for the common multilevel involvement.

PMID- 12518260
TI  - [Influence of postoperative radiation therapy of cerebral metastases on survival
      time and disease related to living condition].
AB  - Cerebral metastases are frequently observed in patients with systemic carcinoma
      as indication for new progress of the disease. Neurological deficits or seizures
      indicating cerebral metastases reduce the disease-related living conditions of
      the patients. Improving quality of life and survival time is the overriding goal
      of an early treatment after the diagnosis of cerebral metastases. Contemporary
      treatment include surgical removal of the cerebral metastases followed by whole
      brain irradiation and in some cases additional systemic chemotherapy for the
      primary tumor. This study was conducted to test the hypothesis that whole brain
      radiation following surgical removal improves the quality of life and the
      survival time in patients with cerebral metastasis. From January 1, 1994 to
      December 31, 2000, a total of 139 patients (mean age 59 +/- 2.3 years, m : f = 84
      : 55) with cerebral metastases were investigated. Disease-related living
      conditions were assessed by Karnofsky score, the median time of follow-up was 11
      months. For the analysis, patients were divided into groups with and without
      radiation therapy. Additionally, groups of patients with singular and two brain
      metastases were defined. In patients with singular brain metastases neither the
      survival time nor disease-related living conditions during the remaining life
      time was increased by postoperative whole brain irradiation. Almost all patients
      died due to the progression of the primary tumor. Patients with more than one
      metastases seemed to have a slight but not significant benefit from irradiation
      therapy after surgical removal of all metastases. In conclusion, these results
      indicate that an uncritical irradiation therapy of neurocranium after surgical
      removal of cerebral metastases is not beneficial in terms of survival time or
      disease-related living conditions.

PMID- 12518261
TI  - [Colonoscopy and sigmoidoscopy in patients aged eighty years or older].
AB  - BACKGROUND: The demographic development will lead to an increase in endoscopic
      examinations in elderly patients. Indications, feasibility and therapeutic
      consequences following detection of pathologic findings are important assessing
      the relevance of endoscopy in geriatric patients. METHODS: We analyzed all
      colonoscopies and sigmoidoscopies which were performed between January 1995 and
      December 2000 in patients older than 80 years. The parameters indication,
      sedation, colonoscopy completion rate, endoscopic findings, therapeutic
      consequences and complications were evaluated. RESULTS: A total of 951
      endoscopies in patients older than 80 years (781 colonoscopies, 170
      sigmoidoscopies; mean age 84.3 years) were performed. The most frequent
      indications were: abdominal pain (n = 144; 15 %), bleeding (n = 115; 12 %),
      constipation (n = 97; 10 %), anemia (n = 85; 9 %), and history of polyps (n = 78;
      8 %). Sedation was used in 183 examinations (19 %), mostly with midazolam (n =
      179). Colonoscopy was completed successfully to the coecum in 71 %. 214
      examinations were unremarkable (23 %). Frequent pathologic findings were:
      diverticular disease (n = 396; 42 %), polyps (n = 256; 27 %), and colorectal
      carcinoma (n = 75; 8 %). Curative surgery was possible in 55 % and palliative
      surgery in 9 % of patients with colorectal carcinoma, respectively. A
      complication was observed in six patients (0.6 %), four bleedings following
      polypectomy, one perforation after dilatation of a stenotic tumor, and one
      transient neurologic deficit. CONCLUSIONS: Endoscopy of the lower
      gastrointestinal tract is feasible in geriatric patients with a low rate of
      complications. The low number of normal findings and the frequent diagnosis of
      colorectal carcinoma were remarkable. In spite of old age more than half of the
      patients with carcinoma could be operated curatively emphasizing the importance
      of endoscopic investigations in this age group.

PMID- 12518262
TI  - [Topical clinical indications for capsule endoscopy -- a paper by the Endoscopy
      Section of DGVS as of 1.11.2002].

PMID- 12518263
TI  - [Chronic diarrhea after a journey to Sri Lanka].
AB  - A 51-year-old woman was referred for evaluation of chronic diarrhea. She had
      spent a 14 day vacation in Sri Lanka three years ago. The clinical examination of
      the patient was unremarkable. Values for protein, iron, zinc, copper and folic
      acid were decreased and the Shilling- and D-xylose tests revealed pathological
      results. Gliadin and Endomysium antibodies were not detectable. Histologic
      examination of the duodenum displayed chronic duodenitis with increased
      epithelial regeneration and villous atrophy. In the MRI a segment of the mid
      small bowel with increased thickness of the intestinal wall was described.
      Abdominal CT-scans demonstrated multiple, enlarged mesenteric lymph nodes.
      Laparoscopy with biopsies of the ileum and mesenteric lymph nodes excluded a
      malignant lymphoma, mycobacteriosis or Whipple's disease. Oral therapy with
      tetracyclines (250 mg q. i. d.) and substitution of folic acid and iron led to
      rapid improvement of the clinical symptoms which persisted after cessation of the
      antibiotic therapy. In view of the clinical course tropical sprue has to be
      assumed despite the short duration of the journey to a tropical region.

PMID- 12518264
TI  - "For whom the bell tolls!" -- innate defense mechanisms and survival strategies
      of the intestinal epithelium against lumenal pathogens.
AB  - The intestinal epithelium serves as an essential defensive barrier of the mucosal
      immune system that forms a bipolar interface between the diverse populations of
      microbes of the lumen and subjacent immune cells present in the lamina propria.
      Intestinal epithelial cells express various pattern recognition receptors --
      poised to recognize microbial "pathogen-associated molecular patterns" as "non
      self" and to rapidly initiate innate immune responses of survival and active
      defense strategies against lumenal pathogens. Current understanding of the
      variety of innate immune features present in intestinal epithelium to maintain
      homeostasis is summarized and the mechanisms through which dysregulation may play
      a central role in initiation and perpetuation of inflammatory bowel disease are
      discussed.

PMID- 12518265
TI  - [Coagulation system and inflammatory bowel disease: therapeutic and
      pathophysiologic implications].
AB  - Several observations are compatible with an association between an haemostatic
      imbalance and the pathogenesis of inflammatory bowel disease. The prothrombotic
      state in Crohn's disease and ulcerative colitis is probably not simply the cause
      of an increased susceptibility for thrombembolic complications, but might also
      reflect an important element of the pathogenetic changes observed in the small
      vessels of the intestinal wall. However, it is still unclear whether alterations
      in the coagulation system are the cause or the aftermath of the systemic
      inflammatory response observed in inflammatory bowel disease. Several recent
      observations describe therapeutic efficacy of unfractioned or low-molecular
      weight heparin in patients with active ulcerative colitis and Crohn's disease.
      Based on these clinical observations new concepts concerning the pathophysiology
      of inflammatory bowel disease have emerged.

PMID- 12518268
TI  - Obesity and related metabolic abnormalities during antipsychotic drug
      administration: mechanisms, management and research perspectives.
AB  - Excessive body weight gain (BWG) is a common side effect of some typical and
      atypical antipsychotic drugs (APs). Convergent evidence suggests a hierarchy in
      the magnitude of BWG that may be induced by diverse agents, being very high for
      clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and
      thioridazine; moderate for risperidone and sertindole; and low for ziprazidone,
      amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. BWG may be
      related to increased appetite that is due to drug interaction with the brain
      monoaminergic and cholinergic systems and to the metabolic/endocrine effects of
      hyperprolactinemia. Subjects with schizophrenia and bipolar disorders manifested
      a significantly high prevalence of diabetes, even before the introduction of
      atypical APs. However, clozapine and olanzapine appear to display a high
      propensity to induce glucose dysregulation and dyslipidemia. Sudden BWG, insulin
      resistance, increased appetite, and related endocrine changes also may be
      involved in the development of glucose intolerance and dyslipidemia in
      predisposed individuals. Patients should be informed of these side effects in
      order to prevent excessive BWG, and their blood glucose and lipids should be
      monitored before treatment and then at regular intervals. Nutritional advice must
      be given and regular physical exercise recommended. An appropriate selection of
      APs ought to be based on drug efficacy for specific patients and assessment of
      relevant risk factors such as propensity to gain weight; family or personal
      history of diabetes or hyperlipidemia; and elevated fasting serum glucose, lipid,
      or insulin levels. At present, there is no standardized pharmacological treatment
      for AP-induced BWG. Some studies have assessed the effects of agents such as
      amantadine, orlistat, metformin, nizatidine, and topiramate on AP-induced BWG.
      Further studies will provide tools to identify patients at high risk for obesity
      and metabolic abnormalities during AP administration. Excessive body weight gain
      (BWG), glucose intolerance, and dyslipidemia during treatment with antipsychotic
      drugs (APs) were reported in the late 1950s [14,101]. However, after 1990,
      interest in these problems increased noticeably, mainly because of the high
      propensity of some new atypical APs to induce these side effects (Fig.1). The APs
      are currently used in diverse mental disorders. Hence, excessive BWG and
      metabolic dysfunction are not exclusive of subjects with schizophrenia. In the
      case of bipolar disorders, AP-induced BWG may be additive to that induced by mood
      stabilizers [14,48,101]. The clinical features [2,14,24,133,139,140] and
      mechanisms [14,34,68,87,93,101,130] of BWG and metabolic dysfunction have been
      previously reviewed. In this article, we focus on a unified theory to explain
      these side effects, based on the interaction of APs with brain neurotransmitters
      involved in appetite regulation. This review comprises the following sections: 1)
      the clinical features of AP-induced BWG; 2) the effects of APs on carbohydrate
      and lipid metabolism in humans and experimental animals; 3) mechanisms involved
      in BWG, glucose, and lipid dysregulation; 4) strategies for prevention and
      treatment of these side effects; and 5) research perspectives in the field. The
      following sources were consulted: MEDLINE, Cochrane database system, and
      PsychINFO. Numerous articles referred to in leading articles also were consulted.
      The literature on this subject has increased so rapidly that it was impossible to
      include all the data recently published. For the first two sections, references
      that illustrate current controversies in the field were selected.

PMID- 12518269
TI  - Body weight, the tumor necrosis factor system, and leptin production during
      treatment with mirtazapine or venlafaxine.
AB  - Weight gain is a frequent and important side effect of psychopharmacotherapy.
      Recent studies suggest that the fat-cell-derived hormone leptin and the tumor
      necrosis factor-alpha (TNF-alpha) cytokine system are pathophysiologically
      involved. No information is available concerning the influence of the
      antidepressants mirtazapine and venlafaxine on these immunoendocrine variables.
      An open-labeled study was performed in 20 patients suffering from major
      depression treated with either mirtazapine (N = 11) or venlafaxine (N = 9).
      During 4 weeks, the patients' weight, body mass index (BMI), and plasma levels of
      leptin, TNF-alpha, sTNF-R p55, and sTNF-R p75 were assessed. Mirtazapine induced
      a significant increase in weight (mean weight gain: 2.4 kg) that was evident
      after the first week of treatment. In parallel, the plasma levels of TNF-alpha
      and both soluble TNF receptors increased. In addition, a slight rise in leptin
      levels, which occurred slowly and was significant only at the end of the 4 th
      week of treatment, was observed. Weight decreased slightly but significantly in
      patients treated with venlafaxine (mean weight loss: 0.4 kg), whereas plasma
      levels of leptin, TNF-alpha, or soluble TNF receptors did not change
      significantly. The present results further support the notion that the activation
      of the TNF-alpha cytokine system is an early, sensitive, and specific marker of
      weight gain induced by psychotropic agents. In contrast, the effects of such
      drugs on leptin production seem to be less sensitive with respect to weight gain
      and more variable.

PMID- 12518270
TI  - Allelic variants of the serotonin(2C) receptor and neuroendocrinological
      responses to the serotonin(2C) receptor agonist m-chlorophenylpiperazine in
      healthy male volunteers.
AB  - The neurotransmitter serotonin (5-HT) possesses several receptors and their
      subtypes, some of which are polymorphic, such as the 5-HT(2C) receptor. The
      latter has been implicated in the control of neuroendocrine function, and has
      been discussed in the pathophysiology and pharmacotherapy of psychiatric
      disorders such as obsessive-compulsive disorder, panic disorder and bipolar
      affective disorder. To investigate whether the 5-HT(2C) receptor polymorphism
      contributes to the variation of neuroendocrinological responses elicited by
      activation of the hypothalamic-pituitary axis, we performed an m
      chlorophenylpiperazine (m-CPP) challenge and monitored m-CPP and ACTH, cortisol
      and prolactin plasma levels in 16 healthy male volunteers carrying the common 5
      HT(2C)-cys-23 receptor gene and 16 healthy male volunteers carrying the less
      frequent 5-HT(2C)-ser-23 receptor gene. The 5-HT(2C) polymorphism contributed
      little to the variation of the scores regarding hormonal responses of ACTH,
      cortisol and prolactin to the m-CPP challenge. The group carrying the rare 5
      HT(2C)-ser-23 receptor gene showed a faster and stronger but not statistically
      significant ACTH response to the challenge. However, it is noteworthy that there
      is a 'medium' effect size of the ACTH response according to the conventions of
      Cohen, and thus comparable to other studies. Both groups show similar major
      scores in the Temperament and Character Inventory (TCI).

PMID- 12518271
TI  - Relationship between risperidone and 9-hydroxy-risperidone plasma concentrations
      and CYP2D6 enzyme activity in psychiatric patients.
AB  - The implication of cytochrome P450 CYP2D6 enzyme activity in the metabolism of
      the antipsychotic drug risperidone has been reported in vitro and in studies of
      healthy volunteers. Around 7 % of Caucasians have inherited impaired capacity of
      this enzyme (poor metabolisers). These subjects might be prone to higher plasma
      concentrations of risperidone. The aim of the study was to determine the
      relationship between the debrisoquine metabolic ratio (MR), a marker of CYP2D6
      enzyme activity, and risperidone plasma levels in psychiatric patients. A
      population of 40 Spanish and Hungarian schizophrenic patients was studied. The
      possible inhibition of CYP2D6 enzyme was also evaluated in a subgroup of patients
      co-medicated with inhibitors of CYP2D6. The risperidone/9-hydroxy-risperidone
      ratio correlated significantly with debrisoquine MR (p < 0.001). In patients co
      medicated with strong inhibitors of CYP2D6, the plasma levels of risperidone (p <
      0.05) and debrisoquine MR (p < 0.01) and risperidone/9-hydroxy-risperidone ratio
      were higher compared to patients with monotherapy. According to the present data,
      the evaluation of the risperidone/9-hydroxy-risperidone ratio may reflect the
      actual enzyme activity of CYP2D6. Therefore, the use of this ratio may help to
      assess potential pharmacokinetic interactions and to improve risperidone
      treatment.

PMID- 12518272
TI  - Treatment of depressive disorders with and without medication - a naturalistic
      study.
AB  - OBJECTIVE: Although randomized clinical trials are the standard method for
      comparing the efficacy of various depression treatments, the external validity
      and generalizability of findings obtained by this approach can be questioned for
      several reasons. In this naturalistic study, we compared the effectiveness of
      treatments conducted by psychiatrists and clinical psychologists without
      prescription of drugs to treatments by psychiatrists and physicians using
      antidepressant agents in patients with depressive disorders in a representative
      sample of the normal population. Our assumption was that this sample is more
      representative for subjects treated for depressive disorders than subjects
      included in controlled trials. METHODS: In a post hoc analysis, the health status
      of depressed patients under treatment for major, minor or recurrent brief
      depression with medication (20 patients) and without medication (30 patients),
      and untreated depressed subjects were compared over a one-year period using SCL
      90-R depression scale scores. RESULTS: At baseline, the two treatment groups were
      comparable in terms of diagnosis and severity of symptoms. Treatment effects were
      relatively small; patients treated with antidepressants tended to improve,
      whereas patients treated without drugs deteriorated slightly over one year. Seven
      years later, treated and untreated subjects no longer differed. CONCLUSION: The
      results are consistent with previous studies on usual care of depressed patients
      showing low response rates for non-standardized treatments outside of research
      settings. Despite a number of methodological shortcomings (small sample size,
      heterogeneity of subjects and treatments, unusual rating instruments), the
      results presented here are unique, and provide relevant insight into usual care
      of depressed patients. This study underlines the importance of standardized
      psychotherapy and pharmacotherapy in routine practice, of studies investigating
      the transferability of results of outcome studies across clinical populations,
      and of quality assurance in primary care psychiatry.

PMID- 12518273
TI  - Prescribing second-generation antipsychotics and the evolving standard of care in
      Italy.
AB  - The present study was carried out to investigate the routine use of second
      generation antipsychotic drugs in the Italian psychiatric care system. Seven
      outpatient psychiatric services enrolled a consecutive case series of patients
      who were being treated, or had started treatment, with clozapine, olanzapine,
      risperidone, or quetiapine. Information on sociodemographic and clinical
      variables, current psychotropic drug use, side-effects and past use of typical
      drugs was collected. In addition, patient symptoms and functional status were
      evaluated by the Health of the Nation Outcome Scale. Patients receiving off-label
      prescribing of second-generation antipsychotics were identified. A total of 209
      patients were collected. In comparison with patients receiving other second
      generation antipsychotics, living in residential facilities, unemployment, long
      psychiatric histories, and problems with activities of daily living and living
      conditions were more common in clozapine-treated patients. Nearly 80 % of
      patients receiving clozapine had schizophrenia compared to less than 50 % of
      those receiving other second-generation antipsychotics. Overall, 109 patients (52
      %) received off-label prescriptions of second-generation antipsychotic drugs.
      This survey indicates that clozapine was mostly reserved for severe cases and
      poor responders; the high rate of off-label prescriptions highlights the gap
      existing between recommendations derived from randomised clinical trials and the
      current use of drugs.

PMID- 12518274
TI  - Initial triple therapy of acute mania, adding lithium and valproate to
      neuroleptics.
AB  - In a closed inpatient unit, valproate and lithium were initially combined in the
      treatment of 12 severely manic patients (ICD-10 F30, F31, F25). Onset of response
      and the use of additional neuroleptic medication were analyzed. For 5 patients a
      comparision was performed between the index episode and a pre-treatment period
      during which lithium therapy was administered without valproate. Outcome criteria
      for the analysis were the latency of response and remission, as well as the dose
      of neuroleptic medication necessary for additional sedation. The mean severity of
      mania syndrome (AMDP-System) in the study patients was comparable to the mean
      mania score of the total manic patient population of the inpatient unit. All
      patients responded to the combination of valproate and lithium, and the mean
      total-remission time was 30 days for the whole group. Mean serum levels were 0.8
      mmol/L for lithium and 73.8 mg/L for valproate. The mean remission time for the 5
      readmitted patients was 22.8 days under combination treatment compared to 35.6
      days in the pre-treatment episode without additional valproate (p = 0.06). It was
      possible to markedly reduce the use of neuroleptic medication in these patients
      from 18 601.6 mg CPZ equivalents to 3927.6 mg (p < 0.025). Initially combining
      valproate and lithium thus appears to be an effective therapeutic option for the
      inpatient management of severe manic syndromes.

PMID- 12518275
TI  - Acute psychosis after administration of bupropion hydrochloride (Zyban).

PMID- 12518278
TI  - Health promotion in middle childhood: the "tween" years.

PMID- 12518276
TI  - The epidemiology of Leber hereditary optic neuropathy in the North East of
      England.
AB  - We performed the first population-based clinical and molecular genetic study of
      Leber hereditary optic neuropathy (LHON) in a population of 2,173,800 individuals
      in the North East of England. We identified 16 genealogically unrelated families
      who harbor one of the three primary mitochondrial DNA (mtDNA) mutations that
      cause LHON. Two of these families were found to be linked genetically to a common
      maternal founder. A de novo mtDNA mutation (G3460A) was identified in one family.
      The minimum point prevalence of visual failure due to LHON within this population
      was 3.22 per 100,000 (95% CI 2.47-3.97 per 100,000), and the minimum point
      prevalence for mtDNA LHON mutations was 11.82 per 100,000 (95% CI 10.38-13.27 per
      100,000). These results indicate that LHON is not rare but has a population
      prevalence similar to autosomally inherited neurological disorders. The majority
      of individuals harbored only mutant mtDNA (homoplasmy), but heteroplasmy was
      detected in approximately 12% of individuals. Overall, however, approximately 33%
      of families with LHON had at least one heteroplasmic individual. The high
      incidence of heteroplasmy in pedigrees with LHON raises the possibility that a
      closely related maternal relative of an index case may not harbor the mtDNA
      mutation, highlighting the importance of molecular genetic testing for each
      maternal family member seeking advice about their risks of visual failure.

PMID- 12518279
TI  - Overview of female middle childhood in societal context: implications for
      research and practice.
AB  - Preadolescence represents a time of becoming and of change less emphasized in
      popular and empirical literature than adolescence. Yet it is an important period
      and a critical time to teach children, while they are still sufficiently adult
      dependent and adult-centered, to help that learning to persist. These are
      formative years during which children experience marked increases in development
      (physical, cognitive, and psychosocial) and knowledge and an incremental shaping
      of values, attitudes, and behaviors that they will carry into adulthood. This
      period of life can also be called the "tween" years, as children during this
      period are transitioning to adolescence. The purpose of this article is to
      present an overview of the societal context in which preteen girls are developing
      and provide some suggestions for testing and implementing health promotion
      strategies that may contribute toward a safe and successful transition for these
      children through adolescence to adulthood in this fast-paced society.

PMID- 12518280
TI  - Female "tweens" and sexual development.
AB  - Sexual development as a component of interpersonal relationships is essential to
      healthy personality development. Nurses, as health professionals who advise and
      counsel "tweens" (early adolescent females) in a variety of settings, have
      important roles to play in promoting their healthy sexual development. To date,
      empirical documentation has contributed to health professionals' ability to
      describe factors that influence early sexual debuts, but it has contributed
      minimally to their understanding of the processes of sexual development. The
      purposes of this article are (a) to generate thoughtful discussions about the
      sexual development of early adolescent females and (b) to discuss how societal
      constructions of female sexual development and identity create particular
      challenges for open communication about sexual expression.

PMID- 12518281
TI  - Special needs of the chronically ill child during middle childhood: application
      of a stress-coping paradigm.
AB  - The "tween years" are often challenging for both the children experiencing this
      period of development and their families. Adding to this challenge could be the
      stress of a chronic illness. This compounded dilemma can alter the achievement of
      normal developmental milestones and disrupt quality of life. This article
      addresses the special challenges of children with chronic illness during the
      tween years and proposes a conceptual framework based on a stress/coping paradigm
      relating chronic illness, coping resources for adaptation, and quality of life
      for research and practice.

PMID- 12518282
TI  - Girls in the juvenile justice system: leave no girl's health un-addressed.
AB  - Despite an increase in middle to older aged adolescent females' early contact
      with the juvenile justice system, inadequate health care remains a concern. This
      descriptive study surveyed the physical and mental health needs of 130 self
      selected, nonrandomized girls aged 12 to 18 years, with a mean age of 15.42 years
      (SD, 1.24), who were involved with a juvenile justice diversional program located
      in a southeastern region of the United States. Findings revealed early initiation
      of sexual-related activities (mean age, 13.9 years; SD, 1.49) and substance use
      (mean age, 12.9 years; SD, 1.53). The data suggest an increasing need for
      pediatric nurses, and in particular advanced practice nurses, to provide gender
      responsive health care and health promotion services to early middle-childhood
      females in the juvenile justice system.

PMID- 12518283
TI  - Parenting and Childhood Chronicity: making visible the invisible work.
AB  - The work required to raise a child with a chronic illness or disability is above
      and beyond that of raising a typical child. This article presents a model,
      Parenting and Childhood Chronicity (PACC), that was developed during an
      interpretive study with 43 parents of 34 children (aged 15 months to 16 years)
      with various chronic conditions, is presented. "Special needs parenting"
      describes the additional care that a child needs and includes medical care,
      parenting plus, and working the systems. "Minimizing consequences" reflects the
      struggle to balance the rest of family life and includes parenting siblings,
      maintaining relationships, and keeping yourself going.

PMID- 12518284
TI  - Children cycling.

PMID- 12518285
TI  - The Parent-Staff Interaction Model of Pediatric Care.
AB  - Nursing models have had a long and often troubled history of development. Many
      that have been developed are not applicable in the pediatric setting. Models of
      pediatric care, though in use in many developing countries, are often not
      applicable within the cultures of those countries. This article outlines the
      history of the development of nursing models, the debate that has accompanied
      their progress, and the way in which they have been applied. An argument about
      the influence of culture on the way children are cared for in hospitals is
      postulated, and explanations are given as to why current models are not
      appropriate for use in pediatrics. A new philosophical model for pediatric
      nursing, the Parent-Staff Interaction Model of Pediatric Care, is presented and
      analyzed using Jacqueline Fawcett's framework for evaluation of nursing models.
      Its applicability to and use in any culture is explained, and feedback for
      further development is requested.

PMID- 12518286
TI  - Using evidence-based practice to create a venous access team: the Venous Access
      Task Force of the Children's Hospital of Denver.
AB  - The following article is an example of evidence-based practice applied to an
      institutional Quality Improvement (QI) project. QI originated in the 1980s and is
      best associated with the work of W. Deming (1986). It is also known as Continuous
      Quality Improvement, because a major principle of this approach is constant
      improvement of services or products. This improvement process contains other
      critical components: scientific method, employee participation and teamwork,
      accountable leadership, appropriate training and ongoing education, and client
      focus (Demming, 1986). QI has been globally successful and has helped transform
      American industry, including health care services. The following clinically based
      project illustrates the application of QI concepts and evidence-based practice to
      enhance outcomes.

PMID- 12518287
TI  - End-of-life care: a priority issue for pediatric nurses.

PMID- 12518288
TI  - Spatiotemporal activation of the two visual pathways in form discrimination and
      spatial location: a brain mapping study.
AB  - To address the question of the relationship between the two visual pathways, a
      ventral stream for object and form vision and a dorsal stream for spatial and
      motion vision, we measured the spatiotemporal activation patterns in the two
      pathways responding to an integrated visuospatial task to which form
      discrimination and spatial location were assigned simultaneously. The two
      cognitive components of form discrimination and spatial location were interwoven
      in the task; however, the fMRI data demonstrated that such a task still activated
      both ventral GTi/GF (the inferior temporal gyrus/the fusiform gyrus) and dorsal
      Ga/PCu (the angular gyrus/Precuneus), which are supposed to mediate form
      discrimination and spatial location, respectively. In addition, the source
      waveforms of the fMRI foci based on the source analysis of the fMRI-seeded dipole
      modeling and the moving dipole modeling indicated that in responding to the task
      combining simultaneously form perception and spatial location, the activity in
      Ga/PCu begins earlier than that in GTi/GF, but it peaks later and lasts longer.

PMID- 12518289
TI  - Dorsal penile nerve stimulation elicits left-hemisphere dominant activation in
      the second somatosensory cortex.
AB  - Activation of peripheral mixed and cutaneous nerves activates a distributed
      cortical network including the second somatosensory cortex (SII) in the parietal
      operculum. SII activation has not been previously reported in the stimulation of
      the dorsal penile nerve (DPN). We recorded somatosensory evoked fields (SEFs) to
      DPN stimulation from 7 healthy adults with a 122-channel whole-scalp
      neuromagnetometer. Electrical pulses were applied once every 0.5 or 1.5 sec to
      the left and right DPN. For comparison, left and right median and tibial nerves
      were stimulated alternatingly at 1.5-sec intervals. DPN stimuli elicited weak,
      early responses in the vicinity of responses to tibial nerve stimulation in the
      primary somatosensory cortex. Strong later responses, peaking at 107-126 msec
      were evoked in the SII cortices of both hemispheres, with left-hemisphere
      dominance. In addition to tactile processing, SII could also contribute to
      mediating emotional effects of DPN stimuli.

PMID- 12518290
TI  - Reconstruction of extended cortical sources for EEG and MEG based on a Monte
      Carlo-Markov-chain estimator.
AB  - A new procedure to model extended cortical sources from EEG and MEG recordings
      based on a probabilistic approach is presented. The method (SPMECS) was
      implemented within the framework of maximum likelihood estimators. Neuronal
      activity generating EEG or MEG signals was characterized by the number of sources
      and their location and extension. Based on the noise distribution of the measured
      data, source configurations were associated with the according value of the
      likelihood function. To find the most likely source, i.e., the maximum likelihood
      estimator, and its level of confidence, a stochastic solver (Metropolis
      algorithm) was applied. The method presented supports the incorporation of
      virtually any constraint, e.g., based on physiological and anatomical a priori
      knowledge. Thus, ambiguity of the ill-posed inverse problem was reduced
      considerably by confining sources to the cortical surface extracted from
      individual MR images. The influence of different levels and types of noise on the
      outcome was investigated by means of simulations. Somatosensory evoked magnetic
      fields analyzed by the method presented suggest that larger extended cortical
      areas are involved in the processing of combined finger stimulation as compared
      to single finger stimulation.

PMID- 12518291
TI  - Power spectrum ranked independent component analysis of a periodic fMRI complex
      motor paradigm.
AB  - Independent component analysis (ICA) has been demonstrated to be an effective
      data-driven method for analyzing fMRI data. However, a method for objective
      differentiation of task-related components from those that are artifactually non
      relevant is needed. We propose a method of constant-cycle (periodic) fMRI task
      paradigm combined with ranking of spatial ICA components by the magnitude
      contribution of their temporal aspects to the fundamental task frequency. Power
      spectrum ranking shares some similarity to correlation with an a priori
      hemodynamic response, but without a need to presume an exact timing or duration
      of the fMRI response. When applied to a complex motor task paradigm with auditory
      cues, multiple task-related activations are successfully identified and separated
      from artifactual components. These activations include sensorimotor, auditory,
      and superior parietal areas. Comparisons of task-related component time courses
      indicate the temporal relationship of fMRI responses in functionally involved
      regions. Results indicate the sensitivity of ICA to short-duration hemodynamics,
      and the efficacy of a power spectrum ranking method for identification of task
      related components.

PMID- 12518292
TI  - Improvement in variability of the horizontal meridian of the primary visual area
      following high-resolution spatial normalization.
AB  - We investigated the decrease in intersubject functional variability in the
      horizontal meridian (HM) of the primary visual area (V1) before and after
      individual anatomical variability was significantly reduced using a high
      resolution spatial normalization (HRSN) method. The analyzed dataset consisted of
      10 normal, right-handed volunteers who had undergone both an O-15 PET study,
      which localized retinotopic visual area (V1), and a high-resolution anatomical
      MRI. Individual occipital lobes were manually segmented from anatomical images
      and transformed into a common space using an in-house high-resolution regional
      spatial normalization method called OSN. Individual anatomical and functional
      variability was quantified before and after HRSN processing. The reduction of
      individual anatomical variability was judged by the reduction in gray matter (GM)
      mismatch and by the improvement in overlap frequency between individual calcarine
      sulci. The reduction in intersubject functional variability of HM was determined
      by measurements of the overlap frequency between individual HM areas and by
      improvement in intersubject Z-score maps. The HRSN processing significantly
      reduced the individual anatomical variability: GM mismatch was reduced by a
      factor of two and the mean calcarine sulcus overlap frequency was improved from
      37 to 68%. The reduction in functional variability was more subtle. However, both
      HM mean overlap (increased from 18 to 28%) and the average Z-score (increased
      from 2.2 to 2.55) were significantly improved. Although, functional registration
      was significantly improved by matching sulci, there was still residual
      variability. This is believed to be the variability of individual areas within
      the calcarine sulcus, and cannot be resolved by sulcal match. Thus, the proposed
      methodology provides an efficient, unbiased, and automated way to study structure
      functional relationship in human brain.

PMID- 12518293
TI  - Ketamine and fMRI BOLD signal: distinguishing between effects mediated by change
      in blood flow versus change in cognitive state.
AB  - No human fMRI studies have examined ketamine effects on the BOLD signal change
      associated with cognitive task performance. We wished to distinguish between
      effects on 1) cerebral blood flow, with resultant change in BOLD signal; and 2)
      cognition and neural mechanisms underlying BOLD signal change associated with
      task performance. Eight right-handed men (mean age 28.75 years) received ketamine
      or saline i.v. in a randomized, double-blind manner (bolus 0.23 mg/kg; 0.5 mg/kg
      over 45 min to a maximum 1 hr). Subjects viewed 10 alternating 30-sec blocks of
      faces with neutral expressions and a fixation cross and discriminated gender of
      faces. Gradient echo echoplanar images were acquired on a GE Signa 1.5 T
      Neurovascular system. One hundred T2-weighted images depicting BOLD contrast were
      acquired over 5 min (for each task) at each of 14 near-axial noncontiguous 7-mm
      thick planes. Ketamine significantly increased dissociative phenomena and
      negative symptoms, but did not affect performance of the gender discrimination
      task. Significant BOLD signal change was demonstrated predominantly in
      occipitotemporal cortex with both ketamine and placebo. Only two clusters in
      middle occipital gyrus (BA 18) and precentral gyrus (BA 4) showed significantly
      decreased BOLD signal change during ketamine compared to placebo. BOLD signal
      change was not significantly greater in any region during ketamine. Our findings
      demonstrate subtle rather than major differences between the effects of ketamine
      and placebo upon the BOLD signal change during perception of face-non face
      contrast. We suggest that they represent task-dependent effects of the
      drug/placebo, rather than task-independent effects of the drug per se, and
      indicate that the effects of ketamine on cerebral blood flow are predominantly
      focal and task-dependent, rather than global and task-independent.

PMID- 12518296
TI  - State of the art review: molecular diagnosis of inherited movement disorders.
      Movement Disorders Society task force on molecular diagnosis.
AB  - This review is designed to provide practical help for the clinical neurologist to
      make appropriate use of the possibilities of molecular diagnosis of inherited
      movement disorders. Huntington's disease, Parkinson's disease and parkinsonian
      syndromes, ataxias, Wilson disease, essential tremor, dystonias, and other
      genetic diseases associated with a variety of movement disorders are considered
      separately.

PMID- 12518297
TI  - Systematic review of incidence studies of Parkinson's disease.
AB  - Incidence studies of Parkinson's disease (PD) are important for both health-care
      planning and epidemiological research. This report reviews the methods and
      results of previous incidence studies of PD and makes recommendations for future
      studies. Original articles that described the incidence of PD were located using
      several strategies. The methods were summarised, and the results of studies with
      similar methodologies were compared on a standardised population. Twenty-five
      incidence studies were included. Each used different methods to identify incident
      patients, although most screened both primary care and hospital records. Only
      eight studies were prospective, and only two of these had any follow-up. The
      diagnostic criteria for PD varied (11 studies used two or more cardinal motor
      features, four used the UK Brain Bank criteria), as did the exclusion criteria
      and the definition of an incident case. In 16 studies, attempts were made to
      confirm the diagnosis by examination of patients by a specialist as part of the
      study. None of the studies used identical methods, but five were sufficiently
      similar to merit comparison. Four of these gave a similar incidence (16
      19/100000/year), but one from Italy had a much lower incidence (8.4/100000), the
      reason for which was unclear. Five studies found significantly greater incidence
      in men. This review highlights the difficulties in performing good quality
      incidence studies of PD. Further incidence studies using standardised methods are
      required. A set of minimal scientific criteria has been devised to improve the
      quality and consistency of future studies.

PMID- 12518298
TI  - Experimental parkinsonism is associated with increased pallidal GAD gene
      expression and is reversed by site-directed antisense gene therapy.
AB  - The levels of mRNA encoding the two isoforms of glutamic acid decarboxylase
      (GAD(65) and GAD(67)) were measured throughout the pallidal complex in normal and
      acutely (i.e., 1 month duration) and chronically (i.e., 5 years duration)
      parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) 
      treated monkeys as well as in monkeys exposed to MPTP but asymptomatic for
      parkinsonism. GAD(65) mRNA labeling was modestly increased in the mid/caudal
      internal globus pallidus (GPi) but not in the external globus pallidus (GPe) in
      parkinsonian monkeys, compared with normal and asymptomatic monkeys. GAD(67) mRNA
      expression was highly increased in the mid/caudal GPi, and modestly increased in
      the GPe in parkinsonian monkeys compared with normal and asymptomatic animals.
      Infusion of GAD(67) antisense oligodeoxynucleotides bilaterally into the GPi
      resulted in a transient reversal of akinesia and bradykinesia that was not
      produced by infusion of missense oligodeoxynucleotides. These data emphasize the
      role of GAD enzyme (particularly GAD(67)) and GABA in the GPi for the expression
      of parkinsonian motor signs and suggest that selective manipulation of GABAergic
      neurotransmission in the GPi may have therapeutic potential for treating
      parkinsonism.

PMID- 12518299
TI  - Deep brain stimulation of the subthalamic nucleus does not increase the striatal
      dopamine concentration in parkinsonian humans.
AB  - Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an
      effective treatment option in advanced Parkinson's disease (PD). Recent animal
      studies showed an increase of neuronal firing in dopaminergic neurons under
      effective STN-DBS. Increased striatal dopamine levels may also contribute to the
      stimulation's mechanism of action in humans. We investigated the striatal
      dopamine release in 6 patients with advanced PD under effective bilateral STN-DBS
      with positron emission tomography (PET) of the reversible dopamine-D2/3-receptor
      ligand [(11)C]raclopride (RACLO). Although STN-DBS proved to be a highly
      effective treatment in these subjects, we found no significant difference of the
      striatal RACLO binding between the STN-DBS-on and -off condition. The changes of
      radioligand binding did not correlate with the patients' improvement in clinical
      rating scales or with the stimulation amplitudes. Therefore, our PET data in
      living parkinsonian humans do not provide evidence for an increased striatal
      dopamine concentration under effective STN-DBS. We conclude that the modulation
      of dopaminergic activity does not seem to play a crucial role for the
      stimulation's mechanisms of action in parkinsonian humans.

PMID- 12518300
TI  - Limb-kinetic apraxia in corticobasal degeneration: clinical and kinematic
      features.
AB  - Current concepts regarding the organisation of the motor system indicate the
      existence of a frontoparietal circuit involved in prehension and manipulation,
      whose damage may result in a motor behavioural disorder strongly resembling the
      one originally described as limb-kinetic apraxia. To determine the specific
      clinical and kinematic features of this distinctive praxic disorder, 5 patients
      with corticobasal degeneration (apraxic group), 5 with Parkinson's disease
      (nonapraxic group), and 10 control subjects were studied by a comprehensive
      apraxic battery, three-dimensional motion analysis of manipulative movements and
      motor evoked potentials. A mathematical model [quality of movement coefficient
      (QMC)] was applied to quantify differential kinematic characteristics between
      elementary motor deficits and the praxic disorder. Transcranial magnetic
      stimulation was used to evaluate corticomotoneural projections and cortical
      inhibition. All five patients in the apraxic group exhibited a unilateral praxic
      deficit characterised by derangement of fractionated and segmental finger
      movements. QMC was significantly greater in apraxic than in nonapraxic patients
      (P < 0.02), revealing a chaotic movement with marked interfinger uncoordination.
      Conventional transcranial magnetic stimulation parameters were within normal
      limits in both groups of patients; however, the silent period was significantly
      shorter in the apraxic limb when compared with control subjects (P < 0.001). Limb
      kinetic apraxia is a distinctive disorder affecting the performance of finger and
      hand postures and movements over and above a corticospinal or basal ganglion
      deficit. Disruption of the frontoparietal circuit devoted to grasping and
      manipulation, together with defective cortical inhibition, which would also
      interfere with the selection and control of hand muscle activity, are the most
      likely underlying physiopathological mechanisms of limb-kinetic apraxia in
      patients with corticobasal degeneration.

PMID- 12518301
TI  - Secondary cervical dystonia associated with structural lesions of the central
      nervous system.
AB  - We tested the hypothesis that structural lesions of the central nervous system
      (CNS) associated with cervical dystonia more commonly involve the cerebellum and
      its primary afferent pathways than basal ganglia structures. Cervical dystonia is
      the most common focal dystonia, the majority of cases are idiopathic, and only a
      small percentage of patients have a family history of dystonia or other movement
      disorders. Pathophysiological mechanisms operative in solely or predominantly
      appendicular dystonias such as writer's cramp and Oppenheim's dystonia,
      respectively, may not be directly applicable to axial dystonias. The localization
      of structural lesions of the CNS associated with secondary cervical dystonia may
      provide some insight into the neural structures potentially involved in primary
      cervical dystonia. The National Library of Medicine Gateway (from 1960) and a
      clinical database maintained by the senior author (from 1999) were searched for
      cases of secondary cervical dystonia associated with structural lesions of the
      CNS. Search terms included one or more of the following: dystonia, torticollis,
      cervical, secondary, and symptomatic. Lesion localization and type, patient age,
      patient gender, head position, occurrence of sensory tricks, and associated
      neurological findings were tabulated for each case. Structural lesions associated
      with cervical dystonia were most commonly localized to the brainstem and
      cerebellum. The remaining cases were equally divided between the cervical spinal
      cord and basal ganglia. Although inconsistent, head rotation tended to be
      contralateral to lesion localization. Additional neurological abnormalities were
      present in the majority of patients with secondary cervical dystonia. The
      relative paucity of basal ganglia pathology and concentration of lesions in the
      brainstem, cerebellum, and cervical spinal cord in patients with secondary
      cervical dystonia suggests that dysfunction of cerebellar afferent pathways may
      be important to the pathophysiology of primary cervical dystonia.

PMID- 12518302
TI  - Automatic assessment of levodopa-induced dyskinesias in daily life by neural
      networks.
AB  - We developed an objective and automatic procedure to assess the severity of
      levodopa-induced dyskinesia (LID) in patients with Parkinson's disease during
      daily life activities. Thirteen patients were continuously monitored in a home
      like situation for a period of approximately 2.5 hours. During this time period,
      the patients performed approximately 35 functional daily life activities.
      Behavior of the patients was measured using triaxial accelerometers, which were
      placed at six different positions on the body. A neural network was trained to
      assess the severity of LID using various variables of the accelerometer signals.
      Neural network scores were compared with the assessment by physicians, who
      evaluated the continuously videotaped behavior of the patients off-line. The
      neural network correctly classified dyskinesia or the absence of dyskinesia in 15
      minute intervals in 93.7, 99.7, and 97.0% for the arm, trunk, and leg,
      respectively. In the few cases of misclassification, the rating by the neural
      network was in the class next to that indicated by the physicians using the AIMS
      score (scale 0-4). Analysis of the neural networks revealed several new
      variables, which are relevant for assessing the severity of LID. The results
      indicate that the neural network can accurately assess the severity of LID and
      could distinguish LID from voluntary movements in daily life situations.

PMID- 12518303
TI  - Prevalence of amyloid-beta deposition in the cerebral cortex in Parkinson's
      disease.
AB  - The pathological basis for the dementia which occurs in 20 to 40% of patients
      with idiopathic Parkinson's disease (PD) remains uncertain. In the present
      postmortem study, we compared the prevalence and severity of parenchymal and
      vascular amyloid-beta (Abeta) deposition in the cerebral cortex in a group of 57
      PD brains, including 13 cases with dementia, and in 100 control brains. A higher
      proportion of PD brains had vascular Abeta deposition, whereas the proportions
      and severity of parenchymal Abeta were similar in the PD and control groups.
      There was a poor correlation between Abeta deposition and neurofibrillary tangles
      which were present in only small numbers in a minority of cases. Cortical Abeta
      deposition was present in only 6 of the 13 cases with dementia and only 3
      fulfilled the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
      criteria for definite Alzheimer's disease. The present findings confirm that
      dementia in PD is only infrequently due to fully established Alzheimer's disease.
      However, vascular and parenchymal Abeta deposition could still contribute to
      dementia and cognitive decline when combined with other changes such as alpha
      synuclein deposition in the cerebral cortex and cortical Lewy bodies.

PMID- 12518305
TI  - Community-based data on associations of disease duration and age with severity of
      essential tremor: implications for disease pathophysiology.
AB  - The pathophysiology of essential tremor (ET) is not well understood, although the
      tremor often worsens over time. Several processes could contribute, including the
      inherent worsening of the underlying disease with increasing disease duration and
      the effects of aging on the nervous system. Our objective was to examine the
      associations of disease duration and age with tremor severity in ET. Cases were
      ascertained from a community-based study of ET in northern Manhattan, New York. A
      neurologist rated tremor severity using a clinical rating scale and assigned a
      total tremor score (0-36 [maximum]). Analyses were repeated in a sample of cases
      from a tertiary referral center, the Neurological Institute of New York. There
      were 55 cases from the community-based study (mean age, 72.1 years, mean disease
      duration, 13.2 years). Disease duration was associated with the total tremor
      score (r = 0.30; P = 0.02). Age was associated with the total tremor score (r =
      0.30; P = 0.025). In a linear regression analysis the dependent variable was the
      total tremor score and independent variables were disease duration, age gender.
      Duration (beta = 0.11; P = 0.02) and age (beta = 0.10; P = 0.02) were
      independently associated with the total tremor score. Results were similar in 79
      ET cases from the Neurological Institute. Disease duration and age were
      independently associated with tremor severity in ET. This suggests that the
      reported increase in tremor severity may be related to the inherent worsening of
      the disease with increasing duration that this is independent of age and age
      related processes like neuronal attrition and change in tremor frequency.

PMID- 12518304
TI  - Treatment of Parkinson's disease in Spain.
AB  - To assess the patterns of drug use in Parkinson's disease in Spain, information
      about the clinical characteristics and current treatment of 1803 parkinsonian
      patients was obtained from a nationwide survey, involving 241 physicians with
      practice based on the different assistance levels of the Spanish National
      Healthcare System. Approximately 90% of the patients were treated with levodopa,
      regardless of the characteristics of their physicians, but the use of the other
      available antiparkinsonian treatments was highly influenced by the medical
      specialty and interest in movement disorders of the prescribing doctors.

PMID- 12518306
TI  - Movement-related cortical potentials before jaw excursions in oromandibular
      dystonia.
AB  - Oromandibular dystonia is a neurological disorder characterized by involuntary
      contraction of masticatory and/or tongue muscles. Cortical negative shifts
      preceding voluntary movements called "movement-related cortical potentials"
      (MRCPs) reflect a central motor control process. Reduced amplitude of MRCPs has
      been reported in other types of dystonia. To elucidate whether the abnormality is
      observed also in oromandibular dystonia, we compared MRCPs associated with
      mandibular movements in 6 patients with this condition and in 8 normal subjects.
      Electroencephalograms (EEGs) were recorded from 11 electrodes, and
      electromyograms (EMGs) were recorded from the masseter muscle and the suprahyoid
      muscles. The subjects were asked to repeat mouth opening, closing, and left and
      right lateral mandibular excursions. MRCPs were obtained by averaging the EEG
      using the EMG onset as the trigger signal. In the patient group, MRCP amplitudes
      over central and parietal areas for mouth opening and lateral movements were
      significantly reduced compared to normal subjects. In normal controls, the MRCPs
      at mouth opening and closing were symmetrically distributed, whereas those at
      lateral movements showed predominance over the hemisphere ipsilateral to the
      direction of the movement. This laterality was lost in the patient group. These
      results suggest impaired cortical preparatory process for jaw movements in
      oromandibular dystonia.

PMID- 12518307
TI  - Spinally generated electromyographic oscillations and spasms in a low-thoracic
      complete paraplegic.
AB  - We have measured some oscillatory properties of severe lower limb spasms
      experienced by a low-thoracic complete paraplegic during assisted standing.
      Electromyograms (EMG) were recorded from the leg muscles while the patient stood
      passively in a standing frame. The patient also stood using functional electrical
      stimulation (FES) while ground and handle reaction force vectors were measured
      together with EMG activity. During passive standing, spasms appeared
      simultaneously in all leg muscle groups on one side. The interval between spasms
      varied between 3 and 30 seconds. Within the spasms, there was a tendency of
      repetitive grouped discharge of motor units as well as a strong 10-Hz component
      in the EMG that was coherent across ipsilateral muscle groups. Thus, the spasms
      were inherently oscillatory. During FES-assisted standing, clinically similar
      spasms were observed. However, the interspasm interval became relatively fixed at
      around 16 seconds, which may indicate entraining of the spasm cycle by FES. There
      are similarities between this patient's spasms and the pathological motor
      activities seen in other movement disorders that may also be of spinal origin.

PMID- 12518308
TI  - Epilepsia partialis continua mistaken for Parkinson's disease.

PMID- 12518309
TI  - Parkinsonism as a manifestation of multiple sclerosis.
AB  - We describe a 48-year-old patient, with a diagnosis of relapsing-remitting
      multiple sclerosis, who presented to our service with a parkinsonian syndrome
      that markedly improved after corticosteroid treatment. To the best of our
      knowledge, only 12 cases of parkinsonism have been reported from 1970 to the
      present, of which only 8 seemed secondary to MS, i.e., those presenting
      conclusive imaging evidence or unequivocal response to corticosteroids.

PMID- 12518310
TI  - Pelvic movements as rhythmic motor manifestation associated with restless legs
      syndrome.
AB  - Video-polysomnographic monitoring of a patient with a 4-year history of an
      unpleasant restless sensation originating in his lower abdomen showed
      stereotyped, repetitive, rhythmic pelvic body movements resembling coital
      behaviour at the wake-sleep transition. We discuss the association between
      restless legs syndrome and rhythmic movement disorder as a particular
      manifestation of a spectrum of rhythmic sleep-related movement disorders.

PMID- 12518311
TI  - Re: Klintenberg et al, tardive dyskinesia model in the common marmoset.

PMID- 12518312
TI  - Valuable tool for patients with orthostatic tremor.

PMID- 12518313
TI  - Review of the iMovie video-editing system.

PMID- 12518314
TI  - Casein kinase II phosphorylates translation initiation factor 5 (eIF5) in
      Saccharomyces cerevisiae.
AB  - Eukaryotic translation initiation factor 5 (eIF5) interacts with the 40S
      initiation complex (40S-eIF3-mRNA-Met-tRNA(f)-eIF2-GTP) to promote the hydrolysis
      of ribosome-bound GTP. In Saccharomyces cerevisiae, eIF5 is encoded by a single
      copy essential gene, TIF5, that is required for cell growth and viability. In
      this work, we show that eIF5 immunoprecipitated from cell-free extracts of (32)P
      labelled yeast cells is phosphorylated on multiple serine residues.
      Phosphopeptide mapping reveals four major sites of phosphorylation that appear to
      be identical to recombinant yeast eIF5 sites phosphorylated in vitro by casein
      kinase II. Furthermore, analysis of eIF5 isolated from a yeast strain having a
      conditional mutant of casein kinase II indicates that phosphorylation of eIF5 is
      completely abolished at the non-permissive temperature. Additionally, haploid
      yeast strains were constructed to contain Ser-to-Ala mutations at the five casein
      kinase II consensus sequences in eIF5; in these cells, eIF5 phosphorylation was
      absent. Surprisingly, substitution of the TIF5 gene mutated at these sites for
      the wild-type gene had no obvious effect on cell growth under normal growth
      conditions. The implications of these results in eIF5 function are discussed.

PMID- 12518315
TI  - Molecular cloning and DNA analysis of a gene encoding alpha mating pheromone from
      the yeast Saccharomyces naganishii.
AB  - A DNA fragment encoding the precursor peptide for alpha mating pheromone was
      isolated from the S. naganishii genome based on the amino acid sequence of the
      mature pheromone. The precursor peptide contains three copies of the pheromone.
      Hydrophobicity analysis of the precursor peptide revealed an N-terminal signal
      sequence for translocation into the lumen of the endoplasmic reticulum and
      several signals for a series of secretion-related processes. However, upstream
      regulatory sequences necessary for expression of the S. cerevisiae alpha mating
      pheromone gene were not found, suggesting the divergence of systems that regulate
      alpha mating pheromone gene expression in S. naganishii and S. cerevisiae.
      Hybridization of a probe corresponding to the S. naganishii alpha mating
      pheromone nucleotide sequence to S. naganishii chromosomal DNA revealed a single
      gene located on either chromosome VI or VII. The S. naganishii alpha mating
      pheromone sequence has been deposited in the DDBJ/EMBL/GenBank data library under
      Accession No. AB086431.

PMID- 12518316
TI  - Metabolic flux analysis of RQ-controlled microaerobic ethanol production by
      Saccharomyces cerevisiae.
AB  - Microaerobic ethanol production by Saccharomyces cerevisiae CBS 8066 was
      investigated at different growth rates in respiratory quotient (RQ)-controlled
      continuous culture. The RQ was controlled by changing the inlet gas composition
      by a feedback controller while keeping other parameters constant. The ethanol
      yield increased slightly from the anaerobic values with decreasing RQ, reaching a
      broad maximum at RQ 20 to 12. There was little or no glycerol production at RQ
      values below 17 over a wide range of dilution rates. Metabolic flux analysis
      revealed that a decrease in the ethanol yield at RQ 6 coincided with the cyclic,
      oxidative operation of the TCA cycle reactions. The model indicated that
      respiratory dissimilation of glucose only occurs when the oxygen uptake rate is
      high enough to completely substitute for glycerol formation. The cytosolic and
      the mitochondrial NADH balances were important for determining the flux
      distributions. The smallest deviations between estimated and measured product
      yields were obtained when the unknown co-factor requirements of a limited number
      of biosynthetic reactions were chosen so that the amount of excess NADH formed in
      biosynthesis was minimized. The biomass yield was positively correlated with the
      net amount of NADH reoxidized in respiration and glycerol formation, indicating
      that the turnover of excess NADH from biosynthesis is an important factor
      influencing the biomass yield under oxygen-limiting conditions.

PMID- 12518317
TI  - Identification of novel protein-protein interactions at the cytosolic surface of
      the Sec63 complex in the yeast ER membrane.
AB  - Precursors of secretory proteins are targeted to the membrane of the endoplasmic
      reticulum by specific protein complexes that recognize their signal sequence. All
      eukaryotic cells investigated so far have been found to possess the signal
      recognition particle (SRP) that targets the majority of precursors to the
      translocation machinery. In Saccharomyces cerevisiae a number of proteins are
      translocated independently of SRP. These precursors rely on a different signal
      sequence-binding complex, which includes Sec62p, Sec63p, Sec71p and Sec72p.
      Identifying interactions between individual components of this tetrameric protein
      complex is important in the understanding of its function. We demonstrate a
      specific interaction between the only two essential proteins in this complex,
      Sec62p and Sec63p. Second, we show evidence of homodimerization of Sec72p
      molecules and further identify the YLR301w gene product as a novel in vivo
      interacting partner of Sec72p. Finally, we determine the authentic N-terminus of
      Sec62p and describe interacting subdomains of both Sec62p and Sec63p.

PMID- 12518318
TI  - Isolation and sequencing of the Candida albicans MSI3, a putative novel member of
      the HSP70 family.
AB  - We have reported previously that the expression of CGR1 increased at an early
      stage of the yeast-mycelial transition (morphogenesis) in Candida albicans. We
      now show that Cgr1p interacts in a yeast two-hybrid system with the C. albicans
      Msi3p (CaMsi3p), a putative novel member of the heat shock protein 70 (HSP70)
      family. The DNA sequence of CaMSI3 encodes a predicted protein of 702 amino acids
      with a molecular mass of 78.6 kDa. The amino acid sequence of CaMsi3p is 63%
      identical to Msi3p/Sse1p of the HSP70 family of Saccharomyces cerevisiae.
      Further, CaMSI3 complemented the temperature-sensitive phenotype of the msi3(-)
      mutant of S. cerevisiae. Other heat shock proteins of C. albicans are required
      for morphogenesis and are highly antigenic. These observations suggest that
      CaMSI3 may well provide functions for this organism unrelated to a heat shock
      function. The DDBJ Accession No. for the sequence reported in this paper is
      AB061274.

PMID- 12518319
TI  - Identification of multicopy suppressors of cell cycle arrest at the G1-S
      transition in Saccharomyces cerevisiae.
AB  - Inactivation of HAL3 in the absence of SIT4 function leads to cell cycle arrest
      at the G(1)-S transition. To identify genes potentially involved in the control
      of this phase of the cell cycle, a screening for multicopy suppressors of a
      conditional sit4 hal3 mutant (strain JC002) has been developed. The screening
      yielded several genes known to perform key roles in cell cycle events, such as
      CLN3, BCK2 or SWI4, thus proving its usefulness as a tool for this type of
      studies. In addition, this approach allowed the identification of additional
      genes, most of them not previously related to the regulation of G(1)-S transition
      or even without known function (named here as VHS1-3, for viable in a hal3 sit4
      background). Several of these gene products are involved in phospho
      dephosphorylation processes, including members of the protein phosphatase 2A and
      protein phosphatases 2C families, as well as components of the Hal5 protein
      kinase family. The ability of different genes to suppress sit4 phenotypes (such
      as temperature sensitivity and growth on non-fermentable carbon sources) or to
      mimic the functions of Hal3 was evaluated. The possible relationship between the
      known functions of these suppressor genes and the progress through the G(1)-S
      transition is discussed.

PMID- 12518320
TI  - Structural characterization of chromosome I size variants from a natural yeast
      strain.
AB  - Many yeast strains isolated from the wild show karyotype instability during
      vegetative growth, with rearrangement rates of up to 10(-2) chromosomal changes
      per generation. Physical isolation and analysis of several chromosome I size
      variants of one of these strains revealed that they differed only in their
      subtelomeric regions, leaving the central 150 Kb unaltered. Fine mapping of these
      subtelomeric variable regions revealed gross alterations of two very similar
      loci, FLO1 and FLO9. These loci are located on the right and left arms,
      respectively, of chromosome I and encompass internal repetitive DNA sequences.
      Furthermore, some chromosome I variants lacking the FLO1 locus showed evidence of
      recombination at a DNA region on their right arm that is enriched in repeated
      sequences, including Ty LTRs. We propose that repetitive sequences in many
      subtelomeric regions in S. cerevisiae play a key role in karyotype
      hypervariability. As these regions encode several membrane-associated proteins,
      subtelomeric plasticity may allow rapid adaptive changes of the yeast strain to
      specific substrates. This pattern of semi-conservative chromosomal rearrangement
      may have profound implications, both in terms of evolution of wild strains and
      for biotechnological processes.

PMID- 12518321
TI  - Effect of soy protein isolate and conjugated linoleic acid on the growth of
      Dunning R-3327-AT-1 rat prostate tumors.
AB  - BACKGROUND: Epidemiologic and animal model studies suggest that consumption of
      soy isoflavones may be associated with reduced risk of prostate cancer (PC). In
      addition, animal model studies suggest that conjugated linoleic acid (CLA), a
      natural positional isomer of linoleic acid, inhibits tumor growth in various
      models, including models of PC. METHODS: Based on the above-mentioned data, the
      objective of the present study was to test the hypothesis that supplementation of
      the diet with combinations of isoflavone-rich soy protein isolate and CLA would
      act to inhibit the growth of androgen-independent R-3327-AT-1 rat prostate tumor
      cells inoculated ectopically into male Copenhagen rats. RESULTS: The results of
      this study indicate that neither an isoflavone-rich soy protein isolate (SPI),
      nor CLA inhibit the in vivo growth and development of prostate tumor cells when
      administered in the diet either singly or in combination. Moreover, at the
      highest concentrations SPI and CLA (i.e., 20% SPI, 1% CLA), there was a
      statistically significant increase in tumors volume over controls. Administration
      of SPI at 10% in the diet also enhanced tumor growth, whereas at 5%, SPI exerted
      no measurable effect. CLA administration alone had no observable effects on AT-1
      tumor growth. CONCLUSION: These results, in an established rat model, suggest
      caution in using isoflavone-rich SPI in human studies involving advanced hormone
      refractory prostate cancer until further investigation of these effects are
      completed.

PMID- 12518322
TI  - The role of human glandular kallikrein 2 for prediction of pathologically organ
      confined prostate cancer.
AB  - BACKGROUND: In recent studies serum levels of human glandular kallikrein 2 (hK2)
      demonstrated significant differences in pathologically organ-confined versus non
      organ-confined prostate cancer (PCa). In this study we investigated whether hK2
      adds independent information when considered together with traditionally used
      parameters to predict organ confined (pT2a/b) PCa. METHODS: Serum levels of hK2,
      total and free prostate-specific antigens (PSA) were obtained one day before
      radical prostatectomy in 245 consecutive men. These were included with clinical
      stage and biopsy Gleason grade into univariate analysis and multivariate logistic
      regression models. RESULTS: pT2a/b PCa was found in n = 148 patients. In
      univariate analysis all preoperative parameters demonstrated significant
      association with the presence of pT2a/b PCa. Using multivariate logistic
      regression model hK2 (P = 0.022), clinical stage (P < 0.0001), and Gleason grade
      (P < 0.0001) were independent predictors of pT2a/b PCa whereas PSA (P = 0.3) was
      not. In bootstrap corrected logistic regression based nomograms the addition of
      hK2 density marginally enhanced predictive accuracy when PSA, PSA density,
      clinical stage, and Gleason grade were considered (AUC = 0.879 without hK2
      density and 0.883 with hK2 density). CONCLUSIONS: hK2 and hK2 density could
      independently predict pT2a/b PCa. However, improvement in predictive accuracy was
      marginal when nomograms based on traditional variables were complemented with
      this serum marker.

PMID- 12518323
TI  - Down-regulated expression of prostasin in high-grade or hormone-refractory human
      prostate cancers.
AB  - BACKGROUND: We previously conducted a search for genes which are differentially
      expressed in hormone-refractory prostate cancers using cDNA-representational
      difference analysis (RDA). The prostasin gene was isolated as one showing down
      regulation in hormone-refractory cancers. In the present study, linkage to the
      stage in prostate neoplasia was examined. METHODS: Prostasin expressions in 54
      prostate cancer cases were examined by mRNA in situ hybridization and
      immunohistochemistry as well as by northern blot analysis. RESULTS: Expression
      levels of prostasin in hormone-refractory cancers were approximately one-sixth of
      those in organ-confined cancers by northern blotting. Glandular components in
      benign prostatic hyperplasia and high-grade prostatic intraepithelial neoplasias
      tended to exhibit mild to moderate and relatively strong intensities,
      respectively. Expression levels of both prostasin mRNA and protein were inversely
      correlated with histological differentiation but not associated with clinical
      stage of human prostate cancer. Almost all cases of metastatic and hormone
      refractory cancers demonstrated down-regulation of prostasin expression.
      CONCLUSIONS: These results suggest that prostasin cannot be regarded as a
      prognostic indicator for human prostate cancer although it may be a useful marker
      for tumor differentiation.

PMID- 12518324
TI  - Experimental therapy of human prostate cancer by inhibiting MDM2 expression with
      novel mixed-backbone antisense oligonucleotides: in vitro and in vivo activities
      and mechanisms.
AB  - BACKGROUND: MDM2 oncogene is overexpressed in many human cancers including
      prostate cancer and MDM2 levels are associated with poor prognosis. This study
      was undertaken to investigate the functions of MDM2 oncogene in prostate cancer
      growth and the value of MDM2 as a drug target for prostate cancer therapy by
      inhibiting MDM2 expression. METHODS: Antisense anti-human-MDM2 mixed-backbone
      oligonucleotide and its mismatch control were tested in in vitro and in vivo
      human prostate cancer models (LNCaP, DU 145, and PC-3) for anti-tumor activity.
      Targeted gene products and related proteins were analyzed and the anti-tumor
      activity was determined when the oligonucleotides were used alone or in
      combination with cancer therapeutics. RESULTS: The antisense oligonucleotide
      specifically inhibited MDM2 expression in a dose- and time-dependent manner,
      resulting in significant anti-tumor activity in vitro and in vivo. In LNCaP
      cells, p53 and p21 levels were elevated. The antisense oligonucleotide also
      potentiated the effects of p53 activation and p21 induction by chemotherapeutic
      agents 10-hydroxycamptothecin, adriamycin, 5-fluorouracil, and paclitaxel. In
      DU145 cells, following inhibition of MDM2 expression, p21 levels were elevated
      although p53 levels remained unchanged. In both cell lines, the antisense
      oligonucleotide inhibited tumor cell growth and induced apoptosis in vitro. In a
      dose-dependent manner, the antisense oligonucleotide showed anti-tumor activity
      in nude mice bearing DU145 or PC-3 xenografts. It significantly increased
      therapeutic effectiveness of the chemotherapeutic agent irinotecan and slightly
      improved the effects of paclitaxel and Rituxan. CONCLUSIONS: These results
      indicate that MDM2 has a role in prostate tumor growth through both p53-dependent
      and p53-independent mechanisms, indicating that MDM2 inhibitors have a broad
      spectrum of anti-tumor activities in human prostate cancers regardless of p53
      status.

PMID- 12518325
TI  - Plasma matrix metalloproteinase 9 as biomarker of prostate cancer progression in
      Dunning (Copenhagen) rats.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play an important role in invasion
      and metastatic spread of cancer cells. The objective of this study was to assess
      MMPs in plasma of Dunning tumor rats as indicators of the progression of prostate
      cancer and follow-up parameters after treatment. METHODS: Prostate cancer was
      induced in male Copenhagen rats by either subcutaneous or orthotopic implantation
      of R3327-MatLyLu cells. During the development of the tumor, plasma MMP-2, and
      MMP-9 were measured by gelatin-substrate zymography and Western blot technique
      with densitometry in untreated animals, rats treated with laser-induced
      hyperthermia, or with the new synthetic MMP inhibitor RO 28-2653. RESULTS: Normal
      prostatic tissue of the Copenhagen rats predominantly expressed proMMP-2 but not
      proMMP-9 whereas MMP-9 was only found in cancerous tissue. Elevated plasma MMP-9
      values were demonstrated in rats with subcutaneous or orthotopic tumors. Animals
      with tumors and treated with the MMP inhibitor RO 28-2653 had both a lower tumor
      volume and a lower plasma MMP-9 concentration compared with controls.
      CONCLUSIONS: The determination of plasma MMP-9 in Dunning tumor rats is a useful
      tool to monitor the progression of prostate cancer and to assess the efficacy of
      drugs like MMP inhibitors or other treatment protocols.

PMID- 12518326
TI  - Quantitation of apoptotic activity following castration in human prostatic tissue
      in vivo.
AB  - BACKGROUND: Androgen deprivation induces apoptosis in the prostate.
      Representative data, quantitating apoptotic activity in human prostatic
      epithelium following androgen ablation, are lacking. METHODS: Human prostatic
      tissue was grafted beneath the renal capsule of intact male athymic mice and
      allowed to become established. The mice were castrated and specimens were
      harvested on post-castration day 0, 1, 2, 3, 4, 5, 7, 8, 9, 10, 14, 17, 18, and
      21. Tissue was immediately fixed and apoptotic epithelial nuclei were identified.
      RESULTS: The percentage of terminal deoxynucleotidyl-transferase-mediated dUTP
      nick end-labeling (TUNEL) positive epithelial cells increased from a baseline of
      0.026%, peaked on post-castration day 3 (1.54%), and returned to baseline by day
      21. Mathematical analysis predicted that the observed apoptotic activity account
      for the loss of 87% of prostatic epithelial cells in 3 weeks. CONCLUSIONS: Post
      castration apoptosis in human prostatic epithelium was low but was sufficient to
      account for the loss of nearly 90% of epithelial cells.

PMID- 12518327
TI  - Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1)
      improve the discrimination between prostate cancer and benign prostatic
      hyperplasia in combination with total and %free PSA.
AB  - BACKGROUND: There is growing evidence describing an association of hK2 and IGFs
      with cancer. The aim of this study is to investigate the differences in serum
      levels of hK2 and IGFs in a large group of patients with benign prostatic
      hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these
      variables, as well as their various combinations with PSA, for discriminating
      between these two clinical entities. METHODS: Human glandular kallikrein 2 (hK2),
      insulin-like growth factor-1 (IGF-1), free and total PSA concentrations were
      measured with non-competitive immunological procedures. Receiver operating
      characteristic (ROC) analysis as well as univariate and multivariate logistic
      regression analysis were performed to investigate the potential utility of the
      various markers and their combinations for discriminating between BPH and CaP.
      RESULTS: hK2 and IGF-1 concentrations were increased in CaP patients, in
      comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under
      the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF
      1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4
      microg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant
      discriminatory value in patients with total PSA within the "gray zone" (4-10
      microg/L). Multivariate logistic regression models confirmed the observed
      relationships and identified IGF-1/free PSA and hK2/free PSA as independent
      predictors of CaP. CONCLUSIONS: hK2/free PSA and IGF-1/free PSA ratios may be
      useful adjuncts in improving patient selection for prostate biopsy.

PMID- 12518328
TI  - Mechanistic investigation of the adrenergic induction of ventral prostate
      hyperplasia in mice.
AB  - BACKGROUND: The norepinephrine (NE) analog phenylephrine has previously been
      shown to induce atypical prostate hyperplasia in rats. The objective of the
      present study was to provide further insight into the mechanism of phenylephrine
      induced prostate growth. METHODS: Adult male C57/BL6 mice were given daily
      subcutaneous injection of phenylephrine, isoproterenol, or phenylephrine in
      combination with BMY7378, cyclazosin, RS100329, or yohimbine, and the effects on
      ventral prostate histology, and proliferative and apoptotic indices determined.
      Phenylephrine was also administered in combination with testosterone in castrated
      mice. RESULTS: Atypical prostatic hyperplasia characterized by piling up and/or
      papillary infolding of epithelial cells with concomitant stromal smooth muscle
      hyperplasia was seen in adult mice given subcutaneous injection of phenylephrine
      daily for 26 days. Phenylephrine induced hyperplasia was more severe proximally
      and was associated with significantly reduced rates of apoptosis (but no change
      in cell proliferation) in both stromal and epithelial compartments. Only the
      alpha(1A)-adrenoceptor selective subtype antagonist RS100329 abrogated the
      phenylephrine-induced hyperplasia. Using selective antibodies, the alpha(1A-1)
      adrenoceptor subtype was predominantly localized to the stromal compartments of
      the mouse and rat ventral prostates. The effects of phenylephrine were mediated
      independent of testicular androgens. CONCLUSIONS: Prostatic hyperplasia in mice
      occurs as a consequence of subchronic administration of the sympathomimetic
      phenylephrine. Response to phenylephrine is mediated by the alpha(1A)
      adrenoceptor, which predominates in the stroma of the rodent ventral prostate.
      Conceivably, therefore, phenylephrine could directly modulate prostate stromal
      growth, and indirectly modulate epithelial growth in a paracrine fashion. We
      cannot, however, rule out the contribution of other indirect effects such as
      hypoxia/reperfusion or effects on intermediary metabolism.

PMID- 12518329
TI  - Prevalence of prostate cancer and prostatic intraepithelial neoplasia in
      Caucasian Mediterranean males: an autopsy study.
AB  - BACKGROUND: The prevalence of carcinoma of the prostate gland (CaP) and high
      grade prostatic intraepithelial neoplasia (HGPIN) was assessed in a Spanish
      population, representative of the Caucasian Mediterranean (CM) ethnic group. Data
      were compared with those described in populations from other geographical regions
      and in other ethnic groups. METHODS: CaP and HGPIN were evaluated in a
      consecutive series of prostatic glands collected at the post-mortem examination
      of 162 male patients born and living in Spain, aged 20-80 years, and dying from
      trauma. The glands were sliced every 2-3 mm. All slices were paraffin embedded
      and sectioned to obtain 5 microm whole-mount sections. To compare the prevalence
      rate in our series and in other Caucasian populations with that from other
      geographical areas and other ethnic groups, we used data from the autopsy study
      performed at the Wayne State University. RESULTS: Prevalence of CaP is 3.58,
      8.82, 14.28, 23.80, 31.7, and 33.33% in the 3rd, 4th, 5th, 6th, 7th, and 8th
      decades, respectively. The rates of HGPIN were 7.14, 11.75, 35.71, 38.06, 45.40,
      and 48.15% at the 3rd, 4th, 5th, and 8th decades of life. Both CaP and HGPIN are
      located preferentially at the peripheral zone of the gland and in 21/27 cases
      (77.7%), an association between CaP and HGPIN was found. The prevalence of both
      lesions in CM males is significantly lower than in Caucasian American (CA) and
      Afro-American (AA) males in all the age groups evaluated. CONCLUSIONS:
      Microscopic foci of CaP and HGPIN can be documented in CM males from the 3rd
      decade of life onwards. The lesions become more frequent and extensive as age
      increases. The prevalence of both lesions seems to be significantly lower in the
      CM population than in CA and AA males in all the age groups evaluated.

PMID- 12518330
TI  - Discovery and design of novel inhibitors of botulinus neurotoxin A: targeted
      'hinge' peptide libraries.
AB  - Intoxication by the zinc protease botulinus neurotoxin A (BoNT-A) results from
      cleavage of a single Q-R bond in the neuronal protein SNAP-25, which disables the
      docking mechanism required for neurotransmitter release. In the present study,
      potential inhibitors of BoNT-A were assessed from their effects on the BoNT-A
      cleavage of a synthetic 17-mer peptide (SNAP-25, residues 187-203) spanning the Q
      R cleavage site. Compounds that inhibited BoNT-A included thiols (zinc chelators)
      such as dithiothreitol, dimercaptopropanesulfonic acid, mercaptosuccinic acid and
      captopril. In addition, compounds containing multiple acidic functions, such as
      the SNARE motif V2 (ELDDRADALQ), the tripeptide Glu-Glu-Glu and the steroid
      glycoside glycyrrhizic acid, were effective inhibitors. 'Hinge' peptide mini
      libraries (PMLs) having the structure acetyl-X(1)-X(2)-linker-X(3)-X(4)-NH(2) or
      X(1)-X(2)-linker-X(3), where X(1)-X(4) were mixtures of selected amino acids and
      the flexible linker was 4-aminobutyric acid, also provided effective inhibition.
      Targeted PMLs containing the acidic amino acids Asp and Glu, the scissile-bond
      amino acids Gln and Arg and the zinc chelators His and Cys produced pronounced
      inhibition of BoNT-A. Deconvolution of these libraries will provide novel ligands
      with improved inhibitory potency as leads in the design of peptide mimetics to
      treat BoNT poisoning.

PMID- 12518331
TI  - Critical analysis of potential body temperature confounders on neurochemical
      endpoints caused by direct dosing and maternal separation in neonatal mice: a
      study of bioallethrin and deltamethrin interactions with temperature on brain
      muscarinic receptors.
AB  - The present investigation was conducted to understand better possible confounding
      factors caused by direct dosing of neonatal mice during the pre-weaning
      developmental period. By direct dosing, pups might encounter thermal challenges
      when temporarily removed from their 'natural habitat'. Typically, this leads to a
      cold environment and food deprivation (impaired lactation) and modulation of the
      toxic potency of the substance administered. Growth retardation as a consequence
      of such behavioural changes in pups makes it increasingly difficult to
      differentiate specific from non-specific mechanisms. Neonatal NMRI mice were
      dosed daily by gavage (0.7 mg kg(-1) body wt.) from postnatal day (PND) 10-16
      with S-bioallethrin, deltamethrin or the vehicle. Then the pups, including their
      non-treated foster dams, were subjected temporarily for 6 h day to a hypo-, normo
      or hyperthermic environment, which was followed by normal housing. The measured
      temperatures in the environmental chambers were ca. 21, 25 and 30 degrees C,
      respectively. Thus, temperatures in the hypo- and normothermic groups are
      comparable to the temperatures commonly present in testing laboratories, whereas
      the hyperthermic condition is that temperature typically present in the 'natural
      habitat' of pups. A deviation from the normal behaviour of both pups and dams was
      observed in the hypo- and normothermic groups. In these groups the rectal
      temperatures of pups were markedly decreased, especially in the early phase of
      the study (PND 10-12). Neonates that received either test substance displayed
      changes in body weights and brain weights at terminal sacrifice (PND 17) when
      subjected temporarily to a non-physiological environment. An enormous influence
      of environmental temperature on the density of muscarinic receptors in the crude
      synaptosomal fraction of the cerebral cortex was ascertained. In summary, these
      results demonstrate that the direct dosing of thermolabile neonatal mice by
      gavage is subject to significant artefacts that render the interpretation of
      findings from such studies difficult. It appears that if direct dosing of
      neonatal pups is mandated, and inhalation is a relevant route of exposure, the
      combined inhalation exposure of dams with their litters is an alternative
      procedure that does not cause disruption of the 'natural habitat' of pups.
      However, owing to their higher ventilation, under such conditions the pups may
      receive dosages at least double those of the dams.

PMID- 12518332
TI  - Effect of single and binary combinations of plant-derived molluscicides on
      different enzyme activities in the nervous tissue of Achatina fulica.
AB  - Effect of single and binary treatments of plant-derived molluscicides on
      different enzymes--acetylcholinesterase (AChE), lactic dehydrogenase (LDH) and
      acid/alkaline phosphatase (ACP/ALP)--in the nervous tissue of the harmful
      terrestrial snail Achatina fulica were studied. Sublethal in vivo 24-h exposure
      to 40% and 80% LC(50) of Azadirachta indica oil, Cedrus deodara oil, Allium
      sativum bulb powder, Nerium indicum bark powder and binary combinations of A.
      sativum (AS) + C. deodara (CD) and CD + A. indica (AI) oils significantly altered
      the activity of these enzymes in the nervous tissue of Achatina fulica. The
      binary treatment of AS + CD was more effective against AChE, LDH, and ALP than
      the single ones. However, binary treatment of AI + CD was more effective against
      ALP.

PMID- 12518333
TI  - Influence of paraoxon (POX) and parathion (PAT) on apoptosis: a possible
      mechanism for toxicity in low-dose exposure.
AB  - The acute effects of poisoning with organophosphorus compounds (OPCs) are well
      known and have been described extensively. Most of the clinical symptoms are due
      to inhibition of acetylcholinesterase. Although acute OPC poisoning is a well
      established clinical entity, the existence of chronic poisoning due to exposure
      to low levels of OPC (below the threshold required for cholinergic clinical
      symptoms) is a hotly debated issue. Recent studies have suggested the involvement
      of OPCs in apoptotic processes. However, the mechanisms by which they modulate
      this process are poorly investigated. In the present study we evaluated the toxic
      effect of different concentrations of paraoxon (POX) and parathion (PAT) in
      murine EL4 T lymphocytes. We examined cellular responses, including induction of
      apoptosis, involvement of a caspase cascade, the activity of effector caspase
      (caspase-3) and the biochemical and morphological changes that are the hallmarks
      of classical apoptosis. The results of our study indicate that at doses below
      IC(50) POX is a potent inducer of apoptosis, as opposed to PAT that shows little
      apoptotic effect.

PMID- 12518334
TI  - Metabolism of a tetraphenyltin compound in rats after a single oral dose.
AB  - The metabolism of tetraphenyltin in rat liver and kidney has been examined.
      Tetraphenyltin and its metabolites in the tissue were determined periodically for
      96 h after a single oral dose of 55.4 mg kg(-1) of tetraphenyltin by gas
      chromatography. The gas chromatographic method was able to determine
      simultaneously both inorganic tin and phenyltin compounds. Although initial (at
      24 h) levels of tetraphenyltin in the liver approximated four times those in the
      kidneys, the levels of tetraphenyltin decreased more rapidly with time than those
      in the kidneys. These findings show that the tetraphenyltin accumulated more
      rapidly and highly in the liver, but was metabolized faster than that in the
      kidney. The levels of total tin in the liver 24 h after treatment were distinctly
      lower than those of di- or triphenyltin treatments in our previous studies and
      none of the animals showed characteristic symptoms. The toxic potencies of
      organotins generally correlate with accumulation of the chemicals. These results
      imply that the slight toxicities of tetraphenyltin might be due to the relatively
      low uptake of tin compounds after ingestion. The highest tin concentration among
      the metabolites of tetraphenyltin in the tissue, especially in liver, was
      observed as diphenyltin throughout the time period studied. These results suggest
      that part of the administered tetraphenyltin may cause some harmful effects as
      diphenyltin in rats, and this must be taken into consideration in toxicological
      research on tetraphenyltin.

PMID- 12518335
TI  - Intravenous pyruvic acid application in minipigs partially protects acetylcholine
      esteratic but not butyrylcholine-esteratic activity in plasma from inhibition by
      paraoxon.
AB  - Intoxications with organophosphorus compounds such as paraoxon (POX) are
      frequent. Oximes are the only enzyme reactivators clinically available. In vitro
      and in vivo studies have shown that l-lactate reduces the inhibition of plasma
      acetylcholine-esteratic activity (AChEA) (in vitro and in vivo) and plasma
      butyrylcholine-esteratic activity (BChEA) (at least in vitro and possibly in
      vivo) by POX. However, a short infusion of 10 g of lactate was unable to elevate
      the plasma lactate level for >3 h. In this study we tested a substance related to
      l-lactate, i.e. pyruvic acid. The purpose of this animal experimental study
      (female minipigs with historical control group) was to determine in vivo whether
      intravenous (i.v.) pyruvic acid application under
      normoxic/normocapnic/normohydrogenaemic conditions is able to elevate blood
      lactate levels and whether it is able to protect AChEA and BChEA from POX
      inhibition. Animals were anaesthetized, intubated and mechanically ventilated.
      Each received 1 mg kg(-1) body wt. of POX in 50 ml of saline over 50 min and 10 g
      (ca. 0.5 g kg(-1) body wt.) of i.v. pyruvic acid in 50 ml of saline over 50 min.
      They were compared with a historical control group of six animals that received
      only 1 mg kg(-1) body wt. of POX in 50 ml of saline over 50 min. In central
      venous blood measurements of plasma AChEA and BChEA, the measurements were
      performed before (baseline), immediately after POX (50 min after start) and 110,
      170, 230, 290, 530 and 1010 min after the start of infusion. A 10 g aliquot of
      i.v. pyruvic acid had a statistically significant protective effect in vivo on
      AChEA but not on BChE activity. Further study of the in vivo effects of pyruvic
      acid and l-lactate after paraoxon intoxication and a formal comparison with
      standard oxime therapy seems warranted. Also, a combination therapy with l
      lactate and pyruvic acid in vivo should be investigated.

PMID- 12518336
TI  - Oestrogenic activity of benzylparaben.
AB  - Previous work has demonstrated that the alkyl esters of p-hydroxybenzoic acid
      (parabens) possess oestrogenic activity, which increases with length of alkyl
      chain from methylparaben to n-butylparaben and with branching in the alkyl chain
      from n-butylparaben to isobutylparaben. This study reports on the oestrogenic
      activity of benzylparaben in a variety of assays in vitro and in vivo.
      Benzylparaben was able to displace [(3)H]oestradiol from cytosolic oestrogen
      receptor (ER) of MCF7 human breast cancer cells by 22% at 1000-fold molar excess,
      by 40% at 10,000-fold molar excess, by 57% at 100 000-fold molar excess and by
      100% at 1,000,000-fold molar excess. It was able to increase expression of a
      stably transfected oestrogen responsive reporter gene (ERE-CAT) in MCF7 cells
      after 24 h at 10(-5)M/10(-4)M and after 7 days at 10(-6)M/10(-5)M/10(-4)M.
      Proliferation of MCF7 cells could be increased by 10(-6)M/10(-5)M benzylparaben
      and this could be inhibited by 10(-7)M pure anti-oestrogen ICI 182,780,
      indicating that growth effects were ER mediated. Further evidence for ER
      mediation was provided from the ability of benzylparaben to increase the growth
      of a second oestrogen-dependent human breast cancer cell line ZR-75-1, but not
      the oestrogen-insensitive MDA-MB-231 cell line. When tested in the presence of
      10(-10)M 17beta-oestradiol, benzylparaben gave no antagonist response on the
      growth of either MCF7 or ZR-75-1 cells. Finally, benzylparaben could increase
      uterine weight in the immature mouse following topical application of three daily
      doses of 33 mg to dorsal skin. These results demonstrate that the oestrogenicity
      of methylparaben can be increased by the addition of an aryl group as well as by
      lengthening or branching the alkyl grouping.

PMID- 12518337
TI  - Toxicity of some bis Mannich bases and corresponding piperidinols in the brine
      shrimp (Artemia salina) bioassay.
AB  - Some acetophenone-derived bis Mannich bases were synthesized: bis[beta
      benzoylethyl]ethylamine hydrochloride (IIa), bis[beta-(p
      methylbenzoyl)ethyl]ethylamine hydrochloride (IIb), bis[beta-(p
      chlorobenzoyl)ethyl]ethy- lamine hydrochloride (IId), bis[(2
      thienylcarbonyl)ethyl]ethylamine hydrochloride (IIe); some corresponding
      piperidinol derivatives: 3-benzoyl-1-ethyl-4-phenyl-4-piperidinol hydrochloride
      (IIIa), 1-ethyl-3-(p-methyl- benzoyl)-4-(p-methylphenyl)-4-piperidinol
      hydrochloride (IIIb), 1-ethyl-3-(p-methoxybenzoyl)-4-(p-methoxy- phenyl)-4
      piperidinol hydrochloride (IIIc), 1-ethyl-3-(p-chlorobenzoyl)-4-(p-chlorophenyl)
      4-piperidinol hydrochloride (IIId), 1-ethyl-4-(2-thienyl)-3-(2-thienylcarbonyl)-4
      piperidinol hydrochloride (IIIe); and some representative quaternary
      piperidinols: 3-benzoyl-1-ethyl-4-hydroxy-1-methyl-4-phenylpiperidinium iodide
      (IIIf), 1-ethyl-4-hydroxy-1-methyl-3-(p-methylbenzoyl)-4-(p
      methylphenyl)piperidinium iodide (IIIg). Toxicity was tested by the brine shrimp
      bioassay as an intermediate test before further in vivo animal experiments.
      Piperidine derivatives were found to be more potent than bis Mannich bases.
      Quaternary piperidine derivatives IIIf and IIIg and also non-quaternary
      piperidine derivatives IIIb, IIIe, IIIc and IIId were more toxic than 5
      fluorouracil in brine shrimp bioassay. Except for IIe, bis Mannich bases were not
      effective. Quaternization and conversion of bis Mannich bases to corresponding
      piperidines improved the toxicity. The lipid solubility of the compounds may not
      affect the toxicity. From these findings the quaternary piperidine derivatives
      IIIf and IIIg could be used in further drug development and also for in vivo
      experiments.

PMID- 12518338
TI  - Application of pharmacokinetic/pharmacodynamic and stochastic modelling to 6
      mercaptopurine micronucleus induction in mouse bone marrow erythrocytes.
AB  - This study investigates the kinetics of bone marrow micronucleated polychromatic
      erythrocytes and some mechanistic aspects of micronuclei induction using
      mathematical models. Female mice were administered a single intraperitoneal
      injection of the purine antagonist 6-mercaptopurine at 50 mg kg(-1). The time
      course evolution of the drug concentrations in the plasma and the micronucleated
      polychromatic erythrocyte kinetic rate in bone marrow were observed. Two
      mathematical models were developed for this study. The first model was built from
      a simultaneous pharmacokinetic/pharmacodynamic approach, but was invalidated
      after comparing its predictions to experimental data. The second model was a
      stochastic model based on some biological hypotheses involved in micronuclei
      induction. This model predicted a wavy kinetic rate of micronucleated
      polychromatic erythrocytes that was confirmed by a second data set obtained from
      a specifically built experimental design. The biological hypotheses were then
      discussed. It turned out from this work that mathematical modelling could be used
      as a tool to explore the cellular mechanisms of toxicity of the compound: for
      instance, the assumptions that 6-mercaptopurine induced micronuclei mainly in
      cells entering the S phase, and not only during the last cell cycle but during
      one of the earlier cycles preceding the extrusion of the main nucleus, were
      confirmed. Moreover, the use of the stochastic model would help to schedule more
      accurately the bone marrow or blood harvesting times in the in vivo rodent
      micronucleus test.

PMID- 12518339
TI  - Protective effects of erdosteine against doxorubicin-induced cardiomyopathy in
      rats.
AB  - The usefulness of doxorubicin (DXR) is limited by its cardiotoxicity. In order to
      improve future DXR therapy by using a new antioxidant agent, an experimental
      study was designed. This study was undertaken to determine whether DXR-induced
      cardiotoxicity is prevented by erdosteine, a mucolytic agent showing antioxidant
      properties. Three groups of male Sprague-Dawley rats (60 days old) were used: one
      group was untreated as a control; the other groups were treated with DXR (single
      i.p. dosage of 20 mg kg(-1) body wt.) or DXR plus erdosteine (10 mg kg(-1) day(
      1), orally), respectively. The DXR treatment without erdosteine increased
      antioxidant enzyme activities and also increased lipid peroxidation in myocardial
      tissue. The rats treated with DXR plus erdosteine produced a significant decrease
      in lipid peroxidation in comparison with control and DXR groups. Furthermore,
      erdosteine administration led to an increase in antioxidant enzyme activities in
      comparison with the control group. Erdosteine treatment also increased the
      activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in comparison
      with the DXR group. There was no significant difference in lipid peroxidation of
      myocardial tissue between control and DXR plus erdosteine-treated rats. It was
      concluded that erdosteine caused an increase in the activities of antioxidant
      enzymes, especially GSH-Px and CAT, protecting the heart tissue sufficiently from
      oxidative damage to membrane lipids and other cellular components induced by DXR.

PMID- 12518341
TI  - Outcome after relapse in an unselected cohort of children and adolescents with
      Ewing sarcoma.
AB  - BACKGROUND: Survival after relapse in patients with Ewing sarcoma is very poor
      and this retrospective study attempts to identify of prognostic factors
      predicting survival after relapse. PROCEDURE: A total of 191 patients with
      localised Ewing sarcoma were registered in the ET-2 trial of the United Kingdom
      Children's Cancer Study Group (UKCCSG). All patients received standardised
      primary treatment with chemotherapy and surgery and or radiotherapy as local
      modality treatment. Sixty-four patients who relapsed are included in this report.
      Treatment at relapse was variable and included chemotherapy, surgery,
      radiotherapy and high dose therapy (HDT) or megatherapy with peripheral stem cell
      transplantation (PBSCT) or autologous bone marrow transplantation (ABMT) in
      various combinations. A subgroup of patients had only non-specific symptomatic
      treatment at relapse. Both univariate and multivariate methods were used to
      investigate variables affecting survival after relapse. RESULTS: The overall
      actuarial median survival from relapse for all patients was 14 months (95% CI 11
      16 months). Univariate analysis showed that males had a longer survival (median,
      16 months vs. 11 months); patients who relapsed while on treatment did worse
      (median, 3 months vs. 16 months) and patients who had a longer disease-free
      interval (DFI) prior to relapse had a better outcome (DFI <1 year, median
      survival = 3 months; DFI 1-2 years, survival = 8 months; DFI > 2 years, median
      survival = 24 months, P < 0.001). Multivariate analysis confirmed that duration
      of first remission was the only factor associated with longer survival after
      relapse. CONCLUSIONS: These data suggest that although aggressive therapy may
      delay disease progression after relapse for some children, the course of the
      disease after relapse is usually fatal. International co-operative studies are
      needed to evaluate new strategies.

PMID- 12518340
TI  - In vitro protection of plasma cholinesterases by metoclopramide from inhibition
      by paraoxon.
AB  - Metoclopramide (MCP) is a dopamine receptor antagonist and serotonine receptor
      agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP
      is a reversible inhibitor of cholinesterases from human central nervous system
      and blood. MCP may have a cholinesterase protective effect against inhibition by
      organophosphates. The purpose of the study was to quantify "in vitro" by means of
      the IC(50)-shift the extent of MCP conferred protection, using paraoxon (POX) as
      an inhibitor. POX is a widely used organophospate responsible for a large number
      of accidental or suicidal exposures. Cholinesteratic activities (ChE) (with
      acetyl-thiocholine (A) and butyryl-thiocholine (B) as substrates) in human plasma
      were measured photometrically in the presence of different POX concentrations and
      IC(50) was calculated. Determinations were repeated in the presence of increasing
      MCP concentrations. It appears that the shift induced by the presence of MCP
      increases with the MCP concentration in a linear manner. In the presence of a
      clinically easily achievable plasma concentration of 1 micro M MCP the IC(50) of
      POX for ChE 'shifts' by a factor of approximately 2-3. The protective effect of
      metoclopramide on cholinesterases could be of practical relevance in the
      treatment of paraoxon poisoning. We conclude that in vivo testing of MCP as an
      organophosphate protective agent is warranted.

PMID- 12518342
TI  - Liver histology after current intensified therapy for childhood acute
      lymphoblastic leukemia: microvesicular fatty change and siderosis are the main
      findings.
AB  - BACKGROUND: During modern intensified therapy for childhood acute lymphoblastic
      leukemia (ALL) serum liver enzymes reach fairly high levels. Since no recent data
      on liver histopathology after therapy are available, we conducted a study of the
      subject. PROCEDURE: Liver biopsy specimens were evaluated and serum liver
      function tests and lipid profiles measured from 27 consecutive children, aged 3.5
      17.6 years, treated according to the regimens for standard (SR) and intermediate
      risk (IR) ALL. RESULTS: None of the patients had entirely normal liver histology.
      Fatty infiltration was detected in 25 out of 27 (93%) and siderosis in 19 out of
      27 patients (70%). Fourteen (52%) had both. Three (11%) also had mild portal
      and/or periportal fibrosis in addition to fatty change and siderosis. Fatty
      change was mainly microvesicular. Siderosis was in most cases grade II/IV to
      III/IV (in 16/19 or 84%). No hepatitis or cirrhosis was found. Serum total and
      LDL-cholesterol levels were higher in the patients with fibrosis than in the
      patients with fatty change (P = 0.036, P = 0.042) or with siderosis +/- fatty
      change (P = 0.036, P = 0.042). In serial ALT measurements a value of 300 U/L or
      more was oftener reached in the fibrosis than in the fatty change or siderosis
      groups (in 33 vs. in 12 or in 4% of the measurements, respectively, P = 0.014, in
      Kruskall-Wallis test). CONCLUSIONS: Microvesicular fatty change and siderosis are
      the main liver findings after current therapy for childhood ALL. Fibrosis occurs
      rarely. High values in serial serum ALT measurements repeatedly or a disturbed
      serum lipid profile may facilitate decisions about the need for a liver biopsy.

PMID- 12518343
TI  - A prospective study of minimally invasive techniques in pediatric surgical
      oncology: preliminary report.
AB  - BACKGROUND: Thoracoscopic and laparoscopic techniques play a major role in
      pediatric surgery. However, minimally invasive surgery (MIS) has not yet
      established itself in pediatric surgical oncology. The authors present a
      prospective study investigating the role of MIS in children with cancer.
      PROCEDURE: All children with abdominal or thoracic tumors requiring surgery were
      registered between September, 2000 and February, 2002. Decisions regarding
      procedures and approaches-conventional or minimally invasive-were made by the
      interdisciplinary team. Data on diagnoses, surgical procedures, complications,
      and conversion rates were registered prospectively. RESULTS: Seventy-four
      patients received 78 operations, 21 (26.9%) of the 78 operations were minimally
      invasive. Seven of 16 tumor biopsies (43.8%) and 9 of 57 tumor resections (15.8%)
      were performed using MIS, which was also exclusively used for diagnostic
      interventions. Conversions to standard techniques only occurred in 5 of 9 tumor
      resections. No major complications were encountered in the MIS group.
      CONCLUSIONS: MIS was practical in every fourth patient in our experience so far.
      It proved to be an excellent approach in diagnostic interventions and tumor
      biopsies, whereas efficacy is limited in tumor resections. Further factors (tumor
      recurrence, trocar site recurrence, tumor growth, and dissemination after CO(2)
      insufflation) have to be evaluated. Our data encourage the continuation of the
      study.

PMID- 12518344
TI  - Treatment of overt extraocular retinoblastoma.
AB  - BACKGROUND: Overt extraocular retinoblastoma is common in developing countries
      and little information about its treatment is available. The aim of this study is
      to report our experience in the treatment of these cases using a uniform
      approach. PROCEDURE: Patients with overt extraocular retinoblastoma including
      orbital extension, preauricular lymph node invasion and/or metastatic disease on
      diagnosis or after extraocular relapse admitted to the Hospital JP Garrahan from
      August 1987 to December 2000 were retrospectively reviewed. Patients were treated
      according to two different protocols (1987-1993 and 1994-2000). Treatment
      included: neoadjuvant combination chemotherapy followed by limited surgery in
      case of orbital extension (enucleation or resection of residual orbital mass) and
      adjuvant chemotherapy and radiotherapy. Chemotherapy included cyclophosphamide,
      vincristine, etoposide, doxorubicin (in protocol 87), idarubicin (in protocol
      94), cisplatin (in protocol 87), and carboplatin (in protocol 94). RESULTS: Forty
      one patients were included. Fifteen of them had orbital or preauricular disease
      and had a 5-year event-free survival (pEFS) of 84%. Twenty-six had distant
      metastatic disease and non survived 5-years. One patient died of toxicity and one
      died in complete remission. One patient had a secondary leukemia. The remaining
      adverse events included CNS and/or systemic relapse. CONCLUSIONS: This treatment
      strategy was highly efficacious for patients with orbital and/or lymph node
      extension. Orbital exenteration is not necessary for these patients. Those
      patients with distant metastatic or CNS disease were not curable with this
      approach.

PMID- 12518345
TI  - Hodgkin disease in ataxia-telangiectasia patients with poor outcomes.
AB  - BACKGROUND: To determine the presenting clinicopathologic features and treatment
      outcomes of 11 ataxia-telangiectasia (A-T) patients with Hodgkin disease.
      PROCEDURE: We reviewed the charts of 412 A-T patients to ascertain cases of
      Hodgkin disease. The data analyzed included date of diagnosis, duration of
      symptoms, chest radiographic findings, stage and histology, therapy, and outcome.
      RESULTS: The six male and five female patients had a median age at diagnosis of
      12.2 years. Eight patients presented with fever, cough, and/or cervical
      lymphadenopathy with a median duration of symptoms of 3 months. Five patients had
      abnormal chest radiographic findings a median of 3 months prior to diagnosis and
      were treated with antibiotics for presumed pneumonia. Mediastinal and hilar
      adenopathy in addition to bilateral infiltrates were present. Histopathology
      reports were available for nine patients. Three had nodular sclerosing and two
      each had lymphocyte depleted, mixed cellularity, and not otherwise specified
      histology. Eight patients had stage IV disease, one had stage III, and in two the
      staging was not documented. Six patients received reduced-dose chemotherapy, two
      received radiation therapy, two did not receive therapy, and in one the treatment
      was not documented. In no patient did the Hodgkin disease remit and all died with
      a median survival of 3 months. Eight died of pneumonia and three of multiple
      system organ failure. CONCLUSIONS: A-T patients with Hodgkin disease have
      markedly reduced survival compared to Hodgkin disease in the general population.
      Their poor outcomes may be due to advanced Hodgkin disease, failure to recognize
      coincident chronic lung disease, and the use of non-standard treatment regimens.

PMID- 12518346
TI  - Neuroblastoma initially presenting as a primary bone tumor: diagnostic value of
      molecular assays for tyrosine hydroxylase.

PMID- 12518348
TI  - Prognostic significance of elevated lactate dehydrogenase and creatine kinase in
      patients with rhabdomyosarcoma.

PMID- 12518349
TI  - Trisomy 5 as the sole abnormality in a case of acute lymphoblastic leukemia.

PMID- 12518350
TI  - Unusual renal mesenchymoma with unknown malignant potential in an infant.

PMID- 12518351
TI  - Interferon alfa-2a in recurrent metastatic hemangiopericytoma.

PMID- 12518352
TI  - Internal thoracic vein cannulation as a complication of central venous catheter
      insertion.

PMID- 12518353
TI  - Vascular endothelial growth factor in monitoring therapy of hepatic
      haemangioendothelioma.

PMID- 12518354
TI  - Successful chemotherapy for melanotic neuroectodermal tumor of infancy in a baby.

PMID- 12518355
TI  - Metastatic malignant rhabdoid tumor of the liver treated with tandem high-dose
      therapy and autologous peripheral blood stem cell rescue.

PMID- 12518356
TI  - Primary intracranial malignant melanoma evolving from leptomeningeal melanosis.

PMID- 12518358
TI  - Fourteen-gauge needle core biopsy of mammographically evident radial scars: is
      excision necessary?
AB  - BACKGROUND: Radial scars are benign lesions that may mimic breast carcinoma on
      mammography and usually are managed by excision biopsy. The authors report their
      experience with stereotactic needle core biopsy (SNCB) in sampling these lesions.
      METHODS: A prospective study examined a consecutive series of 75 mammographically
      detected radial scars from a population-based screening program. In patients who
      were sampled by SNCB followed by surgical biopsy, the histologic findings of core
      biopsy and the gold standard of excision biopsy were compared. RESULTS: Sixty
      three patients were sampled by core biopsy: SNCB was used in 55 patients (87.0%),
      and ultrasound-guided needle core biopsy (UNCB) was used in 8 patients (13%). One
      patient who underwent SNCB did not undergo a follow-up excision biopsy. Radial
      scars were diagnosed preoperatively by core biopsy in 51 of 62 patients who
      underwent excision (82%; 95% confidence interval [95%CI], 70-91%). The
      sensitivity for SNCB was 85% (95%CI, 73-94%), and the sensitivity for UNCB was
      63% (95%CI, 24-91%). Of 54 patients who underwent SNCB and excision, 4 patients
      had coexistent ductal carcinoma in situ (DCIS) at the time they underwent
      surgical excision: SNCB identified DCIS in 1 patient and identified atypical
      ductal hyperplasia (ADH) in 3 patients. In the entire group of 75 radial scars, 5
      scars were associated with DCIS (7%), and there were no invasive carcinomas. ADH
      was present in association with 42 of 74 radial scars that were excised
      surgically (57%). Twenty-nine of those radial scars were sampled preoperatively
      by SNCB. ADH was found in 21 patients (72%; 95CI, 53-87%). CONCLUSIONS: The
      sensitivity of SNCB in the identification of radial scars was 85%. In four
      patients with associated DCIS, SNCB revealed either ADH or DCIS, both of which
      required excision. These findings suggest that patients with SNCB-proven radial
      scars among a screened population can be managed safely by mammographic follow
      up, provided there is no associated DCIS, ADH, or lobular carcinoma in situ.
      Spiculated abnormalities with discordant SNCB results require surgical biopsy.

PMID- 12518359
TI  - Mammography screening matters for young women with breast carcinoma: evidence of
      downstaging among 42-49-year-old women with a history of previous mammography
      screening.
AB  - BACKGROUND: Breast carcinoma is the leading cause of death for women between the
      ages of 40 and 49 years, yet questions linger regarding the effectiveness of
      screening mammography in reducing mortality rates among women of this age. In the
      current study, the authors report on the association between cancer stage at
      diagnosis and a history of mammography screening in a clinical setting that has
      emphasized informed choice regarding mammography screening for women in this age
      group. METHODS: Previous mammographic screening for 247 breast cancer patients 42
      49 years of age who were diagnosed at Kaiser Permanente Colorado during 1994-2000
      was evaluated relative to cancer stage. Cancer stage was dichotomized into early
      (American Joint Committee on Cancer [AJCC] Stages 0 and I) and late (AJCC Stages
      II-IV) and previous screening was defined as at least one normal screening
      mammogram within 24 months before the breast carcinoma diagnosis. RESULTS: Women
      who were screened were less likely to be diagnosed at a late stage than were
      women who were not screened (40% vs. 52% late stage, respectively). Adjusted for
      age, year of diagnosis, and family history, screened women were 0.56 (95%
      confidence interval = 0.32-0.97) times as likely as unscreened women to be
      diagnosed at a late stage. CONCLUSIONS: Women 42-49 of years with breast
      carcinoma who undergo regular screening mammography have a more favorable cancer
      stage than do women with breast carcinoma who do not undergo regular screening.
      This downstaging of breast carcinoma is likely to translate into improved breast
      carcinoma survival resulting from screening mammography for women 40-49 years of
      age.

PMID- 12518360
TI  - Sentinel lymph node versus axillary lymph node dissection for early-stage breast
      carcinoma: a comparison using a utility-adjusted number needed to treat analysis.
AB  - BACKGROUND: The current study was performed to compare the value of sentinel
      lymph node dissection (SND) and axillary lymph node dissection (AND) in improving
      the utility-adjusted survival for early-stage breast carcinoma patients. METHODS:
      A number needed to treat (NNT) analysis was used to compare SND with AND. In the
      NNT equation, 1/(S(SND) - S(AND)), S is the 5-year utility-adjusted survival. A
      literature review was performed to estimate 1) the prevalence of axillary lymph
      node disease for early-stage breast carcinoma, 2) the sensitivity and specificity
      of SND and AND, 3) the 5-year overall survival as a function of axillary lymph
      node involvement, 4) the risk of arm lymphedema as a function of the intervention
      performed, and 5) the utility correction (Uc; impairment of quality of life) for
      arm lymphedema. RESULTS: The NNT method of analysis favored SND over nearly the
      entire range of parameters with a sign change to a negative value occurring only
      as Uc becomes very close to unity. This suggests the superiority of the SND
      approach. Only when there is minimal loss of utility does AND become favored and
      then only minimally. CONCLUSIONS: Compared with AND, SND improves the utility
      adjusted survival in patients with early-stage breast carcinoma. This finding is
      quite robust and was found to remain constant over a range of values for utility
      and lymph node prevalence.

PMID- 12518361
TI  - Primary germ cell tumors in the mediastinum: a 50-year experience at a single
      Japanese institution.
AB  - BACKGROUND: Primary germ cell tumors (GCT) of the mediastinum share similar
      clinical and biologic characteristics, which are different from their testicular
      counterpart. The purpose of the current study was to review the authors'
      institutional experience of mediastinal GCT, emphasizing the clinical spectrum,
      time trends of treatment, and recent advances in therapeutic modalities for
      malignant GCT. METHODS: Between 1951 and 2000, 129 patients (70 males and 59
      females) underwent surgical treatment for GCT, which accounted for 16.0% of the
      mediastinal tumors during the same period. There were 95 patients with mature
      teratomas, 13 patients with seminomas, and 21 patients with nonseminomatous germ
      cell tumors (NSGCT) with median ages of 26.4 years, 27.6 years, and 28.5 years,
      respectively. RESULTS: Adult patients with mature teratomas were less symptomatic
      (33.3%) than pediatric patients (52.4%). All patients with mature teratoma were
      cured by resection alone. Eight of the 13 patients (61.5%) with seminoma were
      symptomatic and 10 of 13 patients (83.3%) survived after surgery and radiation
      with/without chemotherapy. Nineteen of 21 patients (90.5%) with NSGCT had
      dyspnea, chest pain, and superior vena cava syndrome. Before 1985, patients
      received radical resection and/or chemoradiotherapy. However, all patients died
      due to disease progression, with a median survival period of 7.6 months. After
      1986, six of eight patients received cisplatin-based chemotherapy, including
      three who received additional high-dose chemotherapy with a supporting peripheral
      blood stem cell transplantation until tumor markers normalized. Five patients who
      underwent salvage resection are currently disease free with a median survival
      period of 58.3 months. CONCLUSIONS: The institutional experience indicates the
      benign nature of mediastinal mature teratomas and the excellent prognosis for
      patients with seminomas after resection. An improved survival advantage was
      ensured with cisplatin-based preoperative chemotherapy in patients with NSGCT.

PMID- 12518362
TI  - Health related quality of life in prostate carcinoma patients: a systematic
      review of randomized controlled trials.
AB  - BACKGROUND: Health related quality of life (HRQOL) is increasingly reported as an
      important endpoint in cancer clinical trials. However, evidence suggests that
      HRQOL reporting is often inadequate. Given this, the authors undertook a
      systematic review to evaluate HRQOL assessment methodology and reported outcomes
      of randomized controlled clinical trials (RCTs) with prostate carcinoma patients.
      METHODS: A comprehensive search of the literature from 1980 to 2001, mainly on
      the following databases, was undertaken: MedLine, Cancerlit, and the Cochrane
      Controlled Trials Register. Studies were identified according to a predefined
      coding scheme, including HRQOL measure, cultural validity, compliance data
      reported and the clinical significance of the results. RESULTS: Twenty-five RCTs
      were identified, involving 8015 patients primarily with metastatic cancer.
      Bicalutamide was the medical treatment against which most treatment comparisons
      were made. Limitations identified included the fact that only 44% of the studies
      gave a rationale for selecting a specific HRQOL measure, 64% of the studies
      failed to report information about the administration of the HRQOL measure, and
      56% failed to report compliance at baseline. The measure most often used was the
      European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire-Care 30 (EORTC QLQ-C30), although some studies used non-validated
      HRQOL tools. CONCLUSIONS: The current study revealed a lack of a uniform approach
      to HRQOL assessment and several methodologic limitations. It is possible that
      such methodologic limitations have influenced trial findings for HRQOL outcomes.

PMID- 12518363
TI  - A review of p53 expression and mutation in human benign, low malignant potential,
      and invasive epithelial ovarian tumors.
AB  - BACKGROUND: In the current study, the authors present pooled data from studies
      that investigated p53 protein expression and/or mutation in human epithelial
      ovarian tumors. METHODS: The English literature in the MEDLINE, PubMed, and
      Ingenta databases was searched to the end of the year 2000 to identify relevant
      studies. Data were pooled across eligible studies, and the prevalence of p53
      expression and mutation among benign, low malignant potential (LMP), and invasive
      tumors was determined. Prevalence estimates by tumor histology, International
      Federation of Gynecology and Obstetrics (FIGO) stage, and grade also were
      calculated. RESULTS: The pooled prevalence estimate for p53 overexpression among
      epithelial ovarian carcinomas was 51% (95% confidence intervals [95% CI], 50-53%)
      compared with 17% (95% CI, 15-20%) among LMP tumors and 7% (95% CI, 5-10%) among
      benign tumors. p53 mutation prevalence estimates were 45% (95% CI, 42-47%), 5%
      (95% CI, 2-9%), and 1% (95% CI, 0-5%), respectively, for invasive, LMP, and
      benign tumors. The prevalence of these p53 abnormalities was found to be
      associated positively with increasing tumor grade and stage. Differences based on
      histologic subtype also were found. CONCLUSIONS: Although these pooled estimates
      might appear to offer support for various hypotheses regarding the role of p53 in
      ovarian carcinoma, the limitations inherent in these data hamper the
      interpretation of the significance of any of the findings. Future studies will
      require innovative methods to address the limitations of many previous
      investigations and more comprehensive investigation into defective tumor
      suppression mechanisms.

PMID- 12518364
TI  - Patterns of disease recurrence influenced by hematogenous tumor cell
      dissemination in patients with cervical carcinoma of the uterus.
AB  - BACKGROUND: The presence of isolated tumor cells (ITC) in the bone marrow at the
      time of primary diagnosis indicates an increased risk for subsequent development
      of distant metastases in various solid tumors. This study evaluates the
      prevalence and prognostic significance of ITC in patients with primary carcinoma
      of the cervix uteri. METHOD: We immunocytochemically analyzed bone marrow
      aspirates of 130 patients with newly diagnosed carcinoma of the cervix uteri for
      the presence of cytokeratin(CK)-positive cells from May 1994 to January 2001. We
      used a quantitative immunoassay with the monoclonal anti-CK antibody A45-B/B3 and
      evaluated 2 x 10(6) bone marrow cells per patient. Patients were followed
      prospectively for a median of 43 (range, 1-85) months. RESULTS: Isolated tumor
      cells were found in the bone marrow of 38 patients (29%). The presence of ITC did
      not correlate with the International Federation of Gynecology and Obstetrics
      (FIGO) tumor stage (P = 0.61), pelvic and paraaortal lymph node involvement (P =
      0.41), histopathologic grading (P = 0.67), the histologic type of the carcinoma
      (P = 0.93), invasion of lymph nodes (P = 0.93) and blood vessels (P = 0.92), or
      with menopausal status (P = 0.17). The bone marrow status at the time of primary
      diagnosis did not correlate with the overall survival as estimated by Kaplan
      Meier analysis (P = 0.30). However, distant metastases occurred in 5% of the
      patients (n = 5) with negative bone marrow status and in 15% of the patients (n =
      6) with positive bone marrow status (P = 0.054). The median distant disease-free
      survival period was 78 months (95% confidence interval 73-82) in patients with
      negative bone marrow status and 72 months (95% CI 61-82) in patients with
      positive bone marrow status (P = 0.051). Multivariate analysis revealed the
      presence of ITC as a significant, independent risk factor for the subsequent
      development of distant metastases (relative risk 3.6, P = 0.046). CONCLUSION:
      Despite the locoregional predominance of cervical carcinoma at the time of
      primary diagnosis, the presence of ITC in the bone marrow indicates an increased
      risk for the development of distant metastases. This information may prove useful
      to stratify patients for systemic treatment.

PMID- 12518365
TI  - Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients
      with locally advanced squamous cell carcinoma of the head and neck: the Dana
      Farber Cancer Institute experience.
AB  - BACKGROUND: The authors conducted a series of four Phase I-II trials of high-dose
      and intermediate-dose docetaxel, cisplatin, and 5-fluorouracil (TPF)-based
      induction chemotherapy for patients with advanced squamous cell carcinoma of the
      head and neck (SCCHN). The chemotherapy regimens and response rates for each
      trial were published previously. In the current analysis, the authors report the
      data on long-term survival, patterns of failure, and morbidity among the patients
      who were treated at their institution. METHODS: A total of 101 patients with
      previously untreated, locally advanced, curable SCCHN were entered onto the
      studies. Overall, 68 patients (67%) had N2-N3 disease, and 86 patients (85%) had
      Stage IV disease. Patients were treated with combinations of TPF with or without
      leucovorin. Cycles were repeated every 21-28 days for a total of 3 cycles
      followed by hyperfractionated radiotherapy. RESULTS: After a median follow-up of
      49 months, 65 patients (64%) remain alive with no evidence of disease (NED), and
      3 patients remain alive with disease, for an overall survival rate of 67% (68
      patients). Twenty-six patients had locoregional recurrences (LRR), and 5 patients
      had both LRR and distant metastasis (DM). Only five patients had DM as the sole
      site of failure. Four patients underwent salvage surgery at the primary site and
      remain alive with NED. Excluding 17 patients with nasopharyngeal carcinoma, of 84
      patients, 55 patients remain alive with NED (65%). Notably, 43 of 84 patients
      (51%) had oropharyngeal primary tumors, and 30 of those patients remain alive
      with NED (70%). Significant morbidity was low, with two treatment-related deaths.
      All but two of the surviving patients are able to swallow and had their feeding
      tubes removed. CONCLUSIONS: These data suggest that docetaxel adds incrementally
      to the efficacy of cisplatin and fluorouracil. Local-regional failures continue
      to be the major impediment to cure in these patients. Given the increase in local
      regional dose intensity with chemoradiation, sequential treatment plans that
      integrate induction chemotherapy and chemoradiotherapy seem to be the logical
      next step.

PMID- 12518366
TI  - Ciprofloxacin prophylaxis in patients with acute leukemia and granulocytopenia in
      an area with a high prevalence of ciprofloxacin-resistant Escherichia coli.
AB  - BACKGROUND: Infection remains the major cause of morbidity and mortality in
      patients with neutropenia, and the beneficial effects of oral prophylaxis remain
      controversial. METHODS: From 1993 to December 1999, the authors analyzed the
      clinical and microbiologic outcomes of 144 episodes of febrile neutropenia among
      adult patients with acute leukemia. RESULTS: Forty-three consecutive episodes
      occurred among patients who were on ciprofloxacin prophylaxis during 1993-1996
      (ciprofloxacin group), and 101 subsequent episodes occurred among patients who
      were not exposed to ciprofloxacin prophylaxis (control group). There were no
      differences in clinical presentation, antibiotic treatment received for the
      episode, or a worse outcome between groups. The rate of bacteremia was similar
      (12 of 43 patients [28%] vs. 26 of 101 patients [26%], respectively). There was a
      trend toward a higher rate of Gram positive bacteremia in the control group (12
      of 101 patients [12%] vs. 2 of 43 patients [5%]) and a higher rate of Gram
      negative bacteremia in the ciprofloxacin group (11 of 43 patients [26%] vs. 15 of
      101 patients [15%]). Resistance to fluoroquinolones was greater in Escherichia
      coli blood isolates from patients in the ciprofloxacin group (7 of 8 patients vs.
      2 of 9 patients; P = 0.02). CONCLUSIONS: The current results suggest that
      fluoroquinolone prophylaxis for patients with febrile neutropenia may be
      abandoned safely in areas with a high prevalence of ciprofloxacin-resistant
      enterobacteria.

PMID- 12518367
TI  - Cancer in Fanconi anemia, 1927-2001.
AB  - BACKGROUND: Fanconi anemia (FA) is an autosomal recessive disease associated with
      an abnormal response to DNA damage. Although FA is well known for the association
      of aplastic anemia and characteristic birth defects, leukemia and solid tumors
      also occur at a high rate in this group of patients. A review of all reported
      cases is informative with regard to the specific types of cancer, the ages at
      which they occur, and the cumulative probability of their development. METHODS:
      Medline and bibliographies of publications were searched for articles containing
      "Fanconi's anemia" or "aplastic anemia" and all cases of FA from 1927 through
      2001 were included in the database. Cancer cases were identified within these
      reports. Descriptive statistical analyses were performed using Stata7 software.
      RESULTS: One thousand three hundred cases of FA were identified. Nine percent had
      leukemia (primarily acute myeloid leukemia), 7% had myelodysplastic syndrome, 5%
      had solid tumors, and 3% had liver tumors. Patients with cancer were older than
      the cancer-free patients at the time of diagnosis of FA. The median age for
      cancer (including leukemia) was 16, compared with 68 in the general population.
      The most frequent solid tumors were aerodigestive and gynecological carcinomas.
      In approximately 25% of patients with cancer, the malignancy preceded the
      diagnosis of FA. CONCLUSIONS: If the competing risks of aplastic anemia and
      leukemia could be removed, the estimated cumulative probability of development of
      a solid tumor in FA patients is 76% by the age of 45 years. Carcinogenic pathways
      and cancer prevention, surveillance, and treatment can be studied to advantage in
      this genetic model of human cancer.

PMID- 12518368
TI  - The prognostic significance of bone marrow levels of neurofibromatosis-1 protein
      and ras oncogene mutations in patients with acute myeloid leukemia and
      myelodysplastic syndrome.
AB  - BACKGROUND: It has been reported that point mutations of the ras gene occur
      frequently in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
      However, the prognostic significance of ras gene mutations in patients with these
      disorders has been a controversial issue. Although abnormalities in the
      neurofibromatosis 1 (NF1) gene, which is a gene involved in the ras pathway, have
      been observed frequently in patients with juvenile chronic myelogenous leukemia,
      the role of these abnormalities in adult patients with AML or MDS is not clear.
      METHODS: In this study, bone marrow specimens that were obtained from previously
      untreated patients with AML and MDS were examined for ras mutations, and the
      levels of NF1 protein expression were measured. RESULTS: Ras point mutations were
      detected in 16 of 83 patients with AML (19%) and in 21 of 90 patients with MDS
      (23%). Fourteen of 28 patients with chronic myelomonocytic leukemia (50%) had ras
      gene mutations. Decreased bone marrow levels of NF1 protein (< 70% of the median
      level detected in control bone marrow specimens) were observed in 20 of 66
      patients with AML (30.3%) and in 8 of 29 patients with MDS (27.6%); none of the
      patients with ras gene mutations had decreased bone marrow levels of NF1 protein.
      The presence of a mutant ras gene was associated with a shorter complete
      remission duration (CRD) in patients with MDS (P = 0.05) but had no effect on
      survival in patients with AML or MDS. Patients with AML who had decreased NF1
      protein levels had a slightly longer CRD compared with patients who had normal
      NF1 levels (P = 0.07). However, the NF1 level had no significant impact on
      survival among patients with AML or MDS. When patients with low NF1 levels were
      grouped with patients who had ras mutations, the patients who had AML had a
      significantly longer CRD compared with the patients who had MDS (P = 0.02).
      CONCLUSIONS: The current results suggest that a reduction in NF1 protein
      expression and the presence of ras point mutations may complement each other and
      that they both play a complex role in the biology of AML and MDS.

PMID- 12518369
TI  - Liposomal amphotericin B versus the combination of fluconazole and itraconazole
      as prophylaxis for invasive fungal infections during induction chemotherapy for
      patients with acute myelogenous leukemia and myelodysplastic syndrome.
AB  - BACKGROUND: Fungal infections are a major cause of morbidity and mortality in
      patients undergoing induction chemotherapy for acute myelogenous leukemia (AML)
      and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and
      toxicity of liposomal amphotericin B (L-AmB) compared with a combination of
      fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS:
      Patients with newly diagnosed AML or high-risk MDS who were undergoing initial
      induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg
      orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or
      L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label
      study. RESULTS: Seventy-two L-AmB-treated patients and 67 F+I-treated patients
      were enrolled in the study. Of these, 47% of patients completed antifungal
      prophylaxis without a change in therapy for proven or suspected fungal infection.
      Three patients in each arm developed a proven fungal infection. Twenty-three
      percent of the L-AmB-treated patients and 24% of the F+I-treated patients were
      changed to alternative antifungal therapy because of persistent fever (P value
      not significant). Nine percent of the L-AmB-treated patients developed pneumonia
      of unknown etiology compared with 16% of the F+I-treated patients (P value not
      significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L
      AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin
      levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with
      L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients.
      Responses to chemotherapy and induction mortality rates were similar for the two
      arms. CONCLUSIONS: L-AmB and F+I appear similar in their efficacy as antifungal
      prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB
      was associated with higher rates of increased serum bilirubin and creatinine
      levels.

PMID- 12518370
TI  - Clinical significance of vascular endothelial growth factor C and vascular
      endothelial growth factor receptor 3 in patients with nonsmall cell lung
      carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor C (VEGF-C) plays an important role
      in lymphangiogenesis and activates VEGF receptor 3 (VEGFR-3). By contrast,
      lymphatic spread is an important prognostic factor in patients with nonsmall cell
      lung carcinoma (NSCLC). The objective of the current study was to determine
      whether the expression of VEGF-C and VEGFR-3 correlates with clinicopathologic
      factors and prognosis in patients with primary NSCLC. METHODS: The authors
      conducted a retrospective review of 180 consecutive patients who underwent
      complete resection for NSCLC and who did not receive any chemotherapy or
      radiotherapy prior to surgery. Immunohistochemical staining for VEGF-C and VEGFR
      3 was performed. The clinicopathologic implications of VEGF-C and VEGFR-3
      expression were analyzed statistically. RESULTS: Of 180 patients with NSCLC, 137
      patients (76.1%) were positive for VEGF-C, and 40 patients (22.2%) were positive
      for VEGFR-3. VEGF-C expression was observed frequently in patients with
      adenocarcinoma (P = 0.026). For VEGFR-3 expression, significant correlations were
      demonstrated with age (P = 0.02), gender (P = 0.008), and histologic
      differentiation in patients with squamous cell carcinoma (P = 0.03). Patients who
      had positive staining for VEGF-C showed significantly less favorable survival
      rates compared with patients who had negative staining for VEGF-C (P = 0.003).
      The survival rates of patients who had positive staining for VEGFR-3 also were
      significantly lower compared with patients who had negative staining for VEGFR-3
      (P < 0.001). Patients who had positive staining for both VEGF-C and VEGFR-3
      exhibited the most unfavorable prognoses. Univariate analysis revealed the
      following prognostic factors: gender (P = 0.03), tumor status (T1,T2 vs. T3; P <
      0.01), lymph node status (negative vs. positive; P < 0.01), tumor size (< or = 35
      mm vs. > 35 mm; P < 0.01), disease stage (Stage I vs. Stages II and III; P <
      0.01), VEGF-C expression (negative vs. positive; P < 0.01), VEGFR-3 expression
      (negative vs. positive; P < 0.01) and combined VEGF-C and/or VEGFR-3 expression
      (both positive vs. VEGF-C or VEGFR-3 positive; P < 0.01). Multivariate analysis
      demonstrated that VEGFR-3 expression was the only independent negative prognostic
      factor (P < 0.01). CONCLUSIONS: VEGF-C and VEGFR-3 expression may be indicative
      of survival rates for patients with NSCLC.

PMID- 12518371
TI  - A prognostic model and staging for metastatic uveal melanoma.
AB  - BACKGROUND: To identify factors that independently contribute to overall survival
      in Stage IVB uveal melanoma and to subcategorize by prognosis. METHODS: Data of
      91 consecutive patients who died of metastatic uveal melanoma in 1985-2000 were
      analyzed by Kaplan-Meier and Cox regression analysis. Main covariates were
      participation in annual review, symptoms, Karnofsky index, metastatic burden,
      liver function tests, and age. Time on chemotherapy was modeled as a confounder.
      A working formulation for staging patients according to predicted survival was
      designed. RESULTS: Of the 91 patients, 85% underwent annual liver imaging and
      function tests, 63% were asymptomatic, and 73% received chemotherapy. The median
      survival period was 8.4 months (95% confidence interval [CI], 6.3-11.8).
      Karnofsky index, largest dimension of the largest metastasis, metastatic burden,
      serum transaminase, lactate dehydrogenase, and alkaline phosphatase (AP) levels,
      and time on chemotherapy were strongly (P < 0.001) associated with survival.
      Symptoms (P = 0.031) and regular review (P = 0.081) were weakly associated with
      survival. Karnofsky index (P = 0.013), the largest dimension of the largest
      metastasis (P = 0.003), and serum AP level (P = 0.042) retained independent
      significance, adjusting for time on chemotherapy. Predicted median survival
      calculated for relevant covariate combinations was divided into three periods (>
      or =12 months vs. 6-11 months vs. < 6 months). Observed median survival for Stage
      IVBa was 14.9 months (95% CI, 11.7-21.3), for Stage IVBb 8.9 months (95% CI, 2.7
      13.7), and for Stage IVBc 2.0 months (95% CI, 1.0-3.7). CONCLUSION: The model and
      working formulation for categorization can be tested as an aid in patient
      counseling and as a tool in design and analysis of clinical trials.

PMID- 12518372
TI  - Clinical outcome and survival after palliative surgery for spinal metastases:
      palliative surgery in spinal metastases.
AB  - BACKGROUND: The authors sought to identify treatment-related factors that
      influenced survival after surgical treatment for metastatic spinal tumors and to
      evaluate the relationship between survival and postoperative ambulation time as a
      factor related to quality of life. METHODS: The medical records of 81 patients
      with metastatic spinal tumors who underwent palliative surgery at the study
      institution were assessed. Univariate analysis for factors influencing survival
      used the Kaplan-Meier log rank statistic and multivariate analysis used the Cox
      proportional hazards model. The Spearman correlation test was used to analyze the
      relationship between postoperative ambulation and survival time. RESULTS: The
      patients had a median age of 59.9 years and a median survival of 10.6 months
      after surgery. For patients, postoperative ambulatory median survival was 16.5
      months and median ambulation time was 13.8 months. By univariate analysis,
      anatomic site of the primary tumor, postoperative ambulation, and combined
      adjuvant therapy (chemotherapy plus radiotherapy) were associated with prolonged
      survival (P < 0.05). Multivariate analysis identified primary site and
      postoperative ambulatory function as independent predictors of prolonged survival
      (P < 0.0001). Significant correlations were found between ambulation time and
      survival time of patients who were able to walk after surgery (P < 0.0001), even
      in patients with liver (P < 0.05) or lung carcinoma (P < 0.05). CONCLUSIONS: The
      anatomic site of primary carcinoma and postoperative ambulation were associated
      with longer survival after palliative surgery for metastatic spinal tumor. When
      ambulation is attained after surgery, it can be preserved until late in remaining
      life even when the primary tumor is unfavorable. Palliative surgery for spinal
      metastasis can improve the quality and quantity of life.

PMID- 12518373
TI  - The influence of anatomic location on outcome in patients with soft tissue
      sarcoma of the extremity.
AB  - BACKGROUND: The anatomic location of an extremity soft tissue sarcoma may
      influence the patient's presentation, management, and local and systemic
      recurrence rates. The objective of this study was to compare the presentation,
      management, and outcome of patients with soft tissue sarcomas of the upper
      extremity and the lower extremity. METHODS: Prospectively collected data from
      patients who underwent limb-sparing surgery for extremity soft tissue sarcoma
      between January, 1986 and April, 1997 were analyzed. Local recurrence free rates
      and metastasis free rates were calculated using the method of Kaplan and Meier.
      Univariate and multivariate analyses of potential predictive factors were
      evaluated with the log-rank test and the Cox proportional hazards model. RESULTS:
      Of 480 eligible patients, 48 patients (10.0%) had a local recurrence, and 131
      patients (27.3%) developed distant metastasis. The median follow-up of survivors
      was 4.8 years (range, 0.1-12.9 years). Patients with upper extremity tumors had
      smaller lesions (6.0 cm vs. 9.3 cm; P < 0.001), more often underwent unplanned
      excision before referral (89 patients [64.0%] vs. 160 patients [46.9%]; P <
      0.001), and less often received radiotherapy (98 patients [70.5%] vs. 289
      patients [84.8%]; P < 0.001). The 5-year local recurrence free rate was 82% for
      patients with sarcomas of the upper extremity and 93% for patients with sarcomas
      of the lower extremity (P = 0.002). The 5-year metastasis free rate was 82% for
      patients with sarcomas of the upper extremity and 69% for patients with sarcomas
      of the lower extremity (P = 0.013). CONCLUSIONS: Local recurrence was more
      frequent in patients who had sarcomas of the upper extremity compared with
      patients who had sarcomas of the lower extremity. Factors that contributed to
      this difference included histologic type, the use of radiotherapy, and local
      anatomy. Metastasis was more frequent among patients with sarcomas of the lower
      extremity, because those tumors tended to be large and deeper compared with upper
      extremity tumors.

PMID- 12518374
TI  - Racial differences in the outcome of patients with colorectal carcinoma.
AB  - BACKGROUND: African-American (AA) patients with colorectal carcinoma have a worse
      prognosis compared with Caucasians. To analyze the causes of this disparity in
      survival, a retrospective study of patients with colorectal carcinoma was
      undertaken. The impact of treatments received and the role of socioeconomic
      factors such as income, education, and poverty levels were studied. METHODS: A
      retrospective analysis of patients with colorectal carcinoma at a single
      institution was conducted. The overall survival of AA and Caucasians, stage at
      presentation, treatment received, and socioeconomic factors were analyzed using
      the institutional tumor registry and 1990 census data. RESULTS: The overall
      survival of AA patients was worse compared with Caucasians, both due to all
      causes (P < 0.001) and cancer-related deaths (P < 0.001). The relative risk of
      death due to all causes was 1.4 (95% confidence interval [CI] 1.2-1.8) for AA,
      4.3 for patients with Stage IV disease (95% CI 3.2-5.7), and 2.3 for patients not
      undergoing surgery (95% CI 1.7-3.1). After multivariate adjustment for gender,
      site, socioeconomic factors, and therapeutic modalities, the relative risks for
      death were 1.5 (95% CI 1.2) for AA, 1.4 (95% CI 1.1-1.7) for patients 60 years of
      age or older, and 4.2 (95% CI 3.4-5.2) for Stage IV disease. The survival
      difference between AA and Caucasians was not influenced by income, poverty level,
      and education. African Americans were treated less frequently with chemotherapy
      and radiation therapy compared with their Caucasian counterparts. CONCLUSIONS:
      African American patients with colorectal carcinoma have a poorer prognosis
      compared with Caucasians. This discrepancy may be due to decreased utilization of
      chemotherapy and radiation therapy. Socioeconomic factors and lack of access to
      health care do not entirely explain the worse prognosis of AA. These factors
      should be identified and dealt with to improve the health care of AA patients
      with various malignant disorders.

PMID- 12518375
TI  - Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic
      lesions: a report on 18 patients.
AB  - BACKGROUND: Spindle and/or epithelioid melanocytic proliferations that display
      overlapping histopathologic features of Spitz nevus and Spitz-like melanoma are
      diagnostically difficult and controversial melanocytic tumors. There are reports
      of such lesions metastasizing to regional lymph nodes, with a few widely
      disseminating, resulting in death. METHODS: The authors reviewed clinical and
      histopathologic data on all patients with atypical or borderline spitzoid
      melanocytic proliferations who underwent sentinel lymph node biopsy (SLNB). They
      examined how frequently histologically problematic or borderline spitzoid
      melanocytic lesions metastasized to sentinel lymph nodes (SLNs) and which
      clinical or histologic features, if any, predisposed patients to a higher risk
      lesion. RESULTS: Six male patients and 12 female patients, ages 5-32 years (mean,
      16 years), had tumors ranging in size from 1.2 mm to 7.9 mm (mean, 3.5 mm) in
      thickness. Atypical histologic features that were present most frequently
      included incomplete maturation (18 of 18 patients), deep dermal mitoses (16 of 18
      patients), nuclear pleomorphism (10 of 18 patients), and focal sheet-like growth
      (10 of 18 patients). Eight of 18 patients (44%) had SLN metastasis and were
      offered adjuvant treatment. One of eight patients with SLN positive results who
      underwent regional lymphadenectomy had one additional involved lymph node. All 18
      patients were alive and well with no evidence of recurrent or metastatic disease
      after a follow-up of 3-42 months (mean, 12 months). CONCLUSIONS: Histologically
      atypical or borderline spitzoid, melanocytic tumors are diagnostically
      challenging and controversial melanocytic lesions, some of which represent
      unrecognized melanomas. SLNB aids in confirming a diagnosis of melanoma and
      identifies patients who may benefit from early therapeutic lymph node dissection
      and/or adjuvant therapy.

PMID- 12518376
TI  - A prospective cohort study determining the prevalence of thrombotic events in
      children with acute lymphoblastic leukemia and a central venous line who are
      treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement
      in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA)
      Study.
AB  - BACKGROUND: Thrombotic events (TEs) are serious secondary complications in
      children with acute lymphoblastic leukemia (ALL) who receive L-asparaginase (ASP)
      therapy; however, the prevalence of TEs has not been established. The primary
      objective of the Prophylactic Antithrombin Replacement in Kids with Acute
      Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study was to determine
      the prevalence of TEs. The secondary objective was to detect any association of
      TEs with the presence of congenital or acquired prothrombotic disorders. METHODS:
      Children with ALL were screened for TEs at the end of ASP treatment using
      bilateral venograms, ultrasound, magnetic resonance imaging, and
      echocardiography. Symptomatic TEs were confirmed by appropriate radiographic
      tests. All tests were read by a blinded central adjudication committee. RESULTS:
      Twenty-two of 60 children had TEs, a prevalence of 36.7% (95% confidence
      interval, 24.4-48.8%). TEs were located in the sinovenous system of the brain in
      1 patient, the right atrium in 3 patients, and the upper central venous system in
      19 patients. TEs detected by venography resulted in 1) 25-100% occlusion, with 1
      in 3 patients showing occlusion of > 75% of the greatest vessel dimension, and 2)
      the presence of collaterals in 60% of patients, with 40% categorized as major. No
      children with TEs were positive for factor V Leiden or prothrombin gene 20201A,
      and four of eight children with antiphospholipid antibodies had a TE.
      CONCLUSIONS: The prevalence of TEs is exceedingly high in this population, and it
      is likely that the extent of occlusion is likely clinically significant. No trend
      was seen toward an association between TEs and the presence of congenital
      prothrombotic disorders. A trend was seen toward an association between TEs and
      antiphospholipid antibodies. Carefully designed clinical trials of primary
      prophylaxis for the prevention of TEs are required in this patient population.

PMID- 12518377
TI  - Response to preoperative chemoradiation increases the use of sphincter-preserving
      surgery in patients with locally advanced low rectal carcinoma.
AB  - BACKGROUND: Although controversial, some believe that preoperative chemoradiation
      increases the use of sphincter-preserving surgery in low rectal carcinoma
      patients. This article investigates the relationship between objective tumor
      response and sphincter preservation in low rectal carcinoma patients. METHODS:
      The authors reviewed the records of 238 patients with T3 or T4 low rectal
      carcinoma (< or = 6 cm from the anal verge) who underwent preoperative pelvic
      chemoradiation (45 Gy/25 fractions/5 weeks, n = 182 or 52.5 Gy/30 fractions/5
      weeks, n = 56 with continuous infusion 5-fluorouracil at 300 mg/m(2), Monday to
      Friday) followed by mesorectal (n = 223) or local excision (n = 15). A logistic
      regression analysis was used to analyze the influence of objective tumor response
      (defined as complete clinical response) and other prognostic factors on sphincter
      preservation. Because degrees of partial response could not be objectively
      defined retrospectively, the influence of partial response on sphincter
      preservation could not be evaluated. RESULTS: Overall, 49% of patients (117 of
      238) had sphincter-preserving surgery. The clinical complete response rate was
      47%. Independent predictors of sphincter preservation included the year of
      surgery, tumor distance from the anal verge, circumferential tumor involvement,
      and response to chemoradiation. The sphincter preservation rate increased over
      the period of the study (from 28% [December 1989 to December 1992] to 44%
      [January 1993 to December 1996] to 67% [January 1997 to December 2000]). The
      difference in the rates of sphincter preservation according to response was most
      striking among patients with tumors 3 cm or less from the anal verge (44% vs.
      22%, P = 0.01). The pelvic disease recurrence rate among patients undergoing
      sphincter-preserving surgery has been less than 10% since January 1993 and was
      not statistically different between the groups treated from January 1993 to
      December 1996 and from January 1997 to December 2000. CONCLUSIONS: There has been
      an increase in the use of sphincter-preserving surgery without an increase in
      pelvic disease recurrence over the past decade. Although not necessary for
      sphincter preservation, clinical response to preoperative chemoradiation
      independently contributed to sphincter-preserving surgery, particularly in
      patients with low rectal tumors.

PMID- 12518378
TI  - Editorial board's eye view.

PMID- 12518379
TI  - Breathing easy.

PMID- 12518380
TI  - Turning trusts round.

PMID- 12518381
TI  - Child's play.

PMID- 12518382
TI  - Per vagina (PV) bleeding in early pregnancy.

PMID- 12518383
TI  - Acute poisoning: exposure to DIY products.

PMID- 12518384
TI  - Human resource management.

PMID- 12518385
TI  - [Research on superantigenic toxins integrating bacteriology, immunology,
      bacterial toxins, and clinical infections diseases].

PMID- 12518386
TI  - [Gliding motility of mycoplasma--a mechanism cannot be explained by today's
      biology].

PMID- 12518387
TI  - [Function of the Escherichia coli trigger factor].

PMID- 12518388
TI  - [Multidrug efflux pumps of obligately anaerobic bacteria].

PMID- 12518389
TI  - [Strategy against cancer in 21 century, with emphasis of cancer prevention and
      refractory cancer].

PMID- 12518390
TI  - [Liver stem cells and regenerative medicine].

PMID- 12518391
TI  - [HGF therapy to support liver regeneration].

PMID- 12518392
TI  - [The validity of serum acetaminophen concentration at 45 min as an index of
      gastric emptying rate: a study based on pharmacokinetic theories].
AB  - The reliability of the serum acetaminophen (APAP) concentration at 45 min (C45)
      as a measure of gastric emptying (GE) has been evaluated using a pharmacokinetic
      simulation work. The present results have revealed that C45 is a useful index to
      conveniently detect delayed GE, but it is unreliable to measure rapid GE. In
      addition, the following simple criteria for diagnosis of delayed GE has been
      proposed based on the pharmacokinetic theories: after ingestion of 20 mg/kg APAP
      dissolved in a 200 kcal-containing liquid meal, 1) the delayed GE is excluded
      when C45 > 5.0 micrograms/ml, 2) whether GE is delayed or not is inconclusive
      when 2.0 < C45 < 5.0 micrograms/ml, and 3) the delayed GE is confirmed when C45 <
      2.0 micrograms/ml.

PMID- 12518393
TI  - [Transradial approach for transcatheter arterial chemoembolization in patients
      with hepatocellular carcinoma].
AB  - We devised a catheter designed for a transradial artery approach and carried out
      selective hepatic arteriography and transcatheter arterial chemoembolization
      (TACE) in 1999. To evaluate the clinical usefulness and safety of our new
      catheterization, we compared the results of transradial approach with those of
      the conventional transfemoral approach. In 164 (98.9%) of 166 patients in the
      radial group, hepatic arteries and the SMA were successfully visualized by an
      approach via the left radial artery. TACE via the radial artery was attempted in
      all 164 patients in whom the sheath was able to be inserted. When the amount of
      time required from puncture to sheath removal was compared, the two groups of
      patients showed no intergroup difference. Complications occurred in 4 patients
      (2.6%) in the radial group: there were 2 cases of temporary dull pain and 2 cases
      of numbness at the site of puncture, all of which improved after slight release
      of the tourniquet. In conclusion, the present study reported that TACE by our new
      transradial approach was found to have therapeutic efficacy comparable to that of
      the conventional transfemoral approach. This technique is only minimally invasive
      and is associated with few complications. We consider that the transradial artery
      catheterization may become a technique of first choice of TACE.

PMID- 12518394
TI  - [An adult case of acute organoaxial gastric volvulus].

PMID- 12518395
TI  - [A resected case of primary gastric choriocarcinoma].

PMID- 12518396
TI  - [A rupture of splenic artery into the stomach induced by the pressure of splenic
      arterial aneurysm].

PMID- 12518397
TI  - [An autopsy case of cytomegaloviral proctitis similar to acute hemorrhagic rectal
      ulcer].

PMID- 12518398
TI  - [A case of intraluminal duodenal hematoma, supposed to be caused by the rupture
      of the aneurysm].

PMID- 12518399
TI  - [A case of Crohn's disease with osteomalacia detected by bone fracture].

PMID- 12518400
TI  - [Disappearance of basal ganglia hyperintensity on T1-weighted MR images after
      obliterating portal systemic shunt in a patient with hepatic encephalopathy].

PMID- 12518401
TI  - [A case of intrahepatic dissemination of hepatocellular carcinoma after
      radiofrequency ablation therapy with expandable needle electrode].

PMID- 12518402
TI  - [A case of a 85-year-old female with autoimmune hepatitis].

PMID- 12518403
TI  - [A case of primary sclerosing cholangitis (PSC) complicated with acute
      inflammatory demyelinating polyradiculoneuropathy].

PMID- 12518404
TI  - [Discharge planning for the elderly].

PMID- 12518405
TI  - [Drug discovery based on genes].

PMID- 12518406
TI  - [Aging and QOL].

PMID- 12518407
TI  - [Pulmonary tuberculosis in the elderly: the diagnosis and the treatment].

PMID- 12518408
TI  - [Diseases of the eye in the elderly].

PMID- 12518409
TI  - [Urinary incontinence in the elderly--functional assessment and therapy].

PMID- 12518410
TI  - [Endothelium-derived vasoactive factors and atherosclerosis].

PMID- 12518412
TI  - [COPD (chronic obstructive pulmonary disease)].

PMID- 12518411
TI  - [The Japanese Respiratory Society guidelines for management of community-acquired
      pneumonia in adults: a review from the factor of elderly].
AB  - There is little consideration about the elderly factor in JRS and other
      countries' guidelines for management of community-acquired pneumonia (CAP) in
      adults. However, there seem to be several important differences in clinical
      manifestation, managing methods and outcome of pneumonia between young and
      elderly persons. I hope that the detection, management, and strategies to protect
      against pneumonia in the elderly will be included in the next guidelines.

PMID- 12518413
TI  - [Nature of community pharmacy in home care].
AB  - To analyze the reason why home care service which community pharmacists provide
      has not been effectively utilized, a questionnaire on home care services was
      submitted to 472 home care service users, 215 general practitioners, 10 visiting
      nurses and 153 home-helpers, and 75 community pharmacists. We were interested in
      whether or not gaps existed between users' needs, practitioners' demands, and
      pharmacists' awareness of professional responsibility to pharmacy services. Also,
      we were interested in whether or not gaps existed in awareness of the importance
      of cooperation with community pharmacists and influencing factors between
      practitioners and home-helpers and visiting nurses. The main results were as
      follows: users and practitioners considered that counseling about home care and
      welfare services by community pharmacists was important and home visiting was not
      so important. However, pharmacists considered that home visiting was important
      and counseling about home care and welfare services was not so important.
      Therefore, gaps existed between users' needs, practitioners' demands, and
      pharmacists' awareness of professional responsibility to pharmacy services.
      Practitioners' awareness of the importance of cooperation with community
      pharmacists in comparison to that of other professionals was low as well as that
      of home-helpers, and visiting nurses. However, over 70% of them recognized the
      necessity of home visiting services by pharmacists. As far as factors influencing
      the awareness of the importance of cooperation with community pharmacists,
      practitioners' recognition to home visiting by pharmacists was higher than that
      of home-helpers and visiting nurses. However, expectations regarding community
      pharmacists' participation in home care services was higher than that of
      practitioners.

PMID- 12518414
TI  - [Therapeutic effectiveness of ranimustine chemotherapy for essential
      thrombocythemia in the elderly].
AB  - We studied the therapeutic effectiveness of chemotherapy by ranimustine (MCNU)
      for essential thrombocythemia (ET) in 14 ET patients over 60 years of age. The
      median age was 73 years (range: 61-88 years), and the male/female ratio was 6:8.
      The mean platelet counts before chemotherapy was 1,157 +/- 28.4 x
      10(3)/microliter. Five of them had been referred because of thrombotic episodes
      before admission to our hospital, while one was referred because of nasal
      bleeding. The platelet counts were maintained at a level below 500 x
      10(3)/microliter by intravenous administration of MCNU in 12 patients and below
      700 x 10(3)/microliter in two patients. One of the patients suffered cerebral
      infarction during MCNU therapy. No other patient suffered thrombotic episodes
      during MCNU therapy. The patient who was referred because of nasal bleeding had
      no hemorrhagic episode during control of platelet counts by chemotherapy. MCNU
      chemotherapy appears effective for the prevention of thrombosis and bleeding in
      ET.

PMID- 12518415
TI  - [Bone lesions in elderly multiple myeloma].
AB  - We investigated the incidence of bone lesions in elderly cases of multiple
      myeloma (MM) and the course of those lesions, and also evaluated the
      relationships of skeletal symptoms with prognostic factors, and prognosis. The
      subjects were 146 patients, aged 65 years or more (median age 74, range 65-97
      year), who were admitted to 11 institutions between January, 1988 and December,
      1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88
      patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type
      in three patients, and non-secretory type in one patient. Bone lesions in elderly
      MM patients were compared with those in 65 non-elderly MM patients. Skeletal
      symptoms were noted in 104 patients, and bone pain in 75 patients at the time of
      diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26
      patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in
      2 patients and pathologic bone fractures in 53 patients. The occurrence rate of
      osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than
      that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions
      were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%),
      thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion
      in lumbar vertebrae was higher in elderly patients (58.7%) than that in non
      elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71
      patients because of the bone lesions. The relationship between the prognostic
      factors of MM and bone lesions was evaluated. There was a significant difference
      in the serum Ca level between patients with and without bone pain (P < 0.0001)
      and between those with and without pathologic bone fracture (P < 0.01). There was
      a significant difference in the appearance rate of plasma cells in the bone
      marrow between the patients with and without bone lesions (P < 0.05), between
      those with and without bone pain (P < 0.01), and between those with and without
      pathologic fracture (P < 0.05). There was a significant difference in the serum
      beta 2-microglobulin level between the patients with and without bone pain, and
      between those with and without pathologic fracture. There were no significant
      differences in survival times between elderly MM patients with and without bone
      lesions, bone pain and pathological bone fractures, while significant differences
      of survival times were found between non-elderly MM patients with and without
      bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These
      data suggest that there are some differences in bone lesions between elderly and
      non-elderly MM patients.

PMID- 12518416
TI  - [Long-term prognosis and satisfaction after percutaneous endoscopic gastrostomy
      in a general hospital].
AB  - Although percutaneous endoscopic gastrotomy (PEG) has been widely acknowledged as
      a safer method for enteral feeding, its long-term impact on prognosis and quality
      of life (QOL) in elderly patients is not sufficiently understood. Regarding the
      indications of PEG, there still exist issues to be studied due to lack of
      convincing evidence for reduction of expected complications such as aspiration
      pneumonia or for improvement of prognosis in patients with severe dementia. In
      this study we investigated the survival rate after PEG placement and family
      satisfaction retrospectively in 78 elderly inpatients who underwent PEG, by
      sending questionnaires to the patients or their caregivers. The results of 68
      cases (88%) recovered showed that the 1-year survival rate was 64.0%, and the 2
      year survival rate was 55.5%. Fifty-three percent of families of patients showed
      overall satisfaction regarding the induction of PEG. The survival rate was
      relatively higher than that from previously reported studies. The differences we
      observed may be attributed to variations in patients' backgrounds (clinical,
      socio-economic, cultural) in therapeutic interventions. We recognized the
      importance of clarifying factors which would affect the prognosis and QOL in
      elderly patients who undergo PEG. The indication for PEG can be made based on
      comprehensive assessment of the relevant factors in individual cases, taking
      patient's or caregiver's wishes into consideration.

PMID- 12518417
TI  - [Seven cases of remitting seronegative symmetrical synovitis with pitting edema
      (RS3PE) syndrome].
AB  - Among the elderly patients with seronegative polyarthritis, McCarty et al. (1985)
      proposed a disease entity of "remitting seronegative symmetrical synovitis with
      pitting edema (RS3PE) syndrome", but only a few cases have been reported in
      Japan. Here we report 7 cases suspicious of RS3PE syndrome, 2 men and 5 women
      with an average age of 75.9 years, ranging from 67-82 years. Their common
      findings were (1) relatively acute onset, (2) polyarthritis, (3) pitting edema of
      the dorsum of both hands and both feet, and (4) negative rheumatoid factor and
      antinuclear antibody. McCarty et al. found that RS3 PE syndrome was more
      prevalent in men; however, in our experience, the opposite was observed. The
      clinical courses of all patients were good, and they were effectively treated
      either by small dosages of oral prednisolone, nonsteroidal antiinflammatory
      drugs, or Chinese herbal (Kampo) medicines. Since this syndrome might not be rare
      in Japan, it seems necessary to evaluate elderly patients with seronegative
      polyarthritis with pitting edema as RS3PE syndrome in their routine medical
      examinations.

PMID- 12518418
TI  - [An elderly case with sarcoidosis whose symptom of dementia was effectively
      treated by steroid].
AB  - We report a case of a 74-year-old woman whose symptoms of dementia may have been
      caused by sarcoidosis and in whom steroid treatment was effective. The patient,
      who had recieved treatment for hypertension, started to exhibit symptoms of
      dementia one year previously and progressively deteriorated during the month
      before she was admitted. Brain computed tomography showed multiple lacunae
      infarctions. Chest X-ray showed mild swelling of bilateral lymph nodes in the
      mediastinum. The patient was referred to an ophthalmologist because of complaints
      of disturbed visual field, and bilateral uveitis was diagnosed. Negative
      tuberculin, high serum ACE value and high absorbance in the lung hila on Ga
      scintigram were recognized. Lymph node biopsy revealed typical granuloma
      compatible with sarcoidosis. Cerebrospinal fluid (CSF) showed elevated protein
      concentration without an increased cell count. EEG showed a diffuse slow wave
      pattern. We observed the progression of dementia shown by declining scores of
      Mini-Mental State Examination (MMSE) from 17/30 on admission to 7/30 on day 30
      after admission. Although enhanced MRI of the brain showed no typical findings of
      sarcoidosis, we started treatment with prednisolone (50 mg/day) based on the
      suspicion that the progression of dementia was caused by sarcoidosis. One month
      after the start of steroid treatment, we observed gradual improvement of
      symptoms. The MMSE score increased to 20/30. According to previous reports,
      elderly sarcoidosis patients relatively rare by show dementia, but sarcoidosis
      should be considered in the differential diagnosis because steroid treatment can
      be effective.

PMID- 12518419
TI  - [An elderly case suspected of familial hypocalciuric hypercalcemia subsequent to
      manifestation of hypercalcemia].
AB  - Familial hypocalciuric hypercalcemia (FHH) is a relatively rare disease showing
      autosomal dominant heredity. Despite hypercalcemia, it shows a low urinary
      calcium excretion rate, and calcium clearance-creatinine clearance ratio. Since
      the serum calcium level does not increase to more than 12 mg/dl, this disease is
      basically asymptomatic and is incidentally found on medical examinations in many
      cases. However, it sometimes presents dangerous hypercalcemia and requires
      treatment. In this disease, parathyroidectomy is not sufficiently effective to
      cure hypercalcemia. We encountered a female patient with advanced age who
      presented marked hypercalcemia. Several examinations suggested FHH. While we had
      difficulty in controlling the serum calcium level, periodic administration of
      alendronate sodium hydrate, a bone resorption inhibitor, was effective. In this
      patient, the serum calcium level was normal on the examination about a year and a
      half before the appearance of symptoms, and hypercalcemia manifested itself in
      her advanced age, which is different from the usual course of FHH. This case
      presumably suggests that the pathophysiology of FHH is varied.

PMID- 12518420
TI  - [Role of toll-like receptor in innate immunity].

PMID- 12518421
TI  - [Functional roles of TLR4/MD-2 and RP105/MD-1 in innate recognition of LPS].

PMID- 12518422
TI  - [The regulatory role of V alpha 14 NKT cells in innate and acquired immune
      response].

PMID- 12518423
TI  - [Regulation of cell adhesiveness through an inhibitory receptor].

PMID- 12518424
TI  - [A novel immune receptor family, MAIR-I and II, involved in positive and negative
      regulation of innate immunity].

PMID- 12518425
TI  - [Evolution of NK cell receptors and virus].

PMID- 12518426
TI  - [Immune regulation by dendritic cells].

PMID- 12518427
TI  - [Regulatory mechanism of DC function by IL-15].

PMID- 12518428
TI  - [Viral strategies of interference with MHC functions].

PMID- 12518429
TI  - [Immune system and ubiquitin supersystem].

PMID- 12518430
TI  - [Prethymic and intrathymic pathway of T cell development].

PMID- 12518431
TI  - [Commitment into the lymphoid lineage].

PMID- 12518432
TI  - [Visualization of thymocyte development].

PMID- 12518434
TI  - [B cell development through preB cell receptor signaling].

PMID- 12518433
TI  - [Accessibility control of the TCR gamma locus by the IL-7 receptor].

PMID- 12518435
TI  - [Lnk, an adaptor protein regulate production of B cells and hematopoietic stem
      cells].

PMID- 12518436
TI  - [A critical role of the CDM family molecule DOCK2 in lymphocyte migration].

PMID- 12518437
TI  - [Regulation of integrin-mediated adhesion and migration by Rap1].

PMID- 12518438
TI  - [Lymphocyte subsets and chemokine receptors].

PMID- 12518439
TI  - [Chondroitin sulfate proteoglycan, common ligand of L-selectin and CD44].

PMID- 12518440
TI  - [Chemokines and lymphocyte homing].

PMID- 12518441
TI  - [Molecular mechanism of immunological synapse formation].

PMID- 12518442
TI  - [T cell membrane raft domains: its function in T cell activation].

PMID- 12518443
TI  - [Immunoregulatory role for BCAP in B cell development and function].

PMID- 12518444
TI  - [Regulation of B lymphocyte activation and tolerance by costimulation and co
      receptors].

PMID- 12518445
TI  - [Involvement of immune semaphorins in the immune system].

PMID- 12518446
TI  - [p38 MAP kinase in the immune response].

PMID- 12518447
TI  - [Molecular regulatory mechanism of Fas-mediated apoptosis].

PMID- 12518448
TI  - [Signal(s) from B cell antigen receptors and apoptotic cell death of immature B
      cells].

PMID- 12518449
TI  - [Role of SOCS/CIS/SSI molecules in Th1/Th2 differentiation and allergic immune
      disease].

PMID- 12518450
TI  - [Th1/Th2 cell differentiation processes that regulated by polycomb group gene
      products].

PMID- 12518451
TI  - [Memory B cells: new light on their regulation].

PMID- 12518452
TI  - [Role of GANP in B cell activation].

PMID- 12518453
TI  - [A role for Bcl6 in immune memory development].

PMID- 12518454
TI  - [Role of cytokines for maintenance of memory CD8+ T cells].

PMID- 12518455
TI  - [Development and physiological functions of intraepithelial lymphocytes in the
      intestinal mucosa].

PMID- 12518456
TI  - [M cells: development and function].

PMID- 12518457
TI  - [T cell mediated immunoregulation and autoimmune disease].

PMID- 12518458
TI  - [Abnormal gp130 signaling and autoimmune disease].

PMID- 12518459
TI  - [Abnormalities on physiological IFN signal as the cause of the skin disease].

PMID- 12518460
TI  - [The role of IL-1 in the development of autoimmunity].

PMID- 12518462
TI  - [IL-18 and atopic inflammation].

PMID- 12518461
TI  - [Induction of SOCS family proteins in inflammatory diseases and suppression of
      inflammatory arthritis model by the adenovirus gene transfer].

PMID- 12518463
TI  - [Aberrant high expression of B lymphocyte chemoattractant (BLC/CXCL13) in a
      murine model for SLE].

PMID- 12518464
TI  - [Immune dysfunctions in Fc receptor-deficient mice].

PMID- 12518465
TI  - [Regulation of experimental autoimmune encephalomyelitis by NK and NKT cells].

PMID- 12518466
TI  - Mind as healer, mind as slayer: MindBody medicine comes of age.

PMID- 12518467
TI  - Somatic metaphor: a clinical phenomenon pointing to a new model of disease,
      personhood, and physical reality.
AB  - The rarely discussed phenomenon of somatic metaphor is apparent when a physical
      disease--in its pathology, the organ(s) involved, and/or its body location-
      appears to be "saying" the same thing, expressing the same meaning, as the
      patient's subjective "story," conveyed in verbal language or in the pattern of
      important and meaningful events in the life of the patient. The author offers
      evidence that when patients presenting for diagnosis and treatment of physical
      disease are appraised from both normative physicalist and psychotherapy
      perspectives, somatic metaphors are frequently observed. Building on clinical
      examples, the crucial role of the clinician in observing (or failing to observe)
      this conjunction of physical disease and personal meaning is analyzed; a visual
      modeling of clinician patterns of observation is provided to facilitate
      clinicians in moving away from simplistic, reductionistic, observer patterns so
      that they may accommodate physical and "story" perspectives in the same clinical
      space; biomedical and biopsychosocial models are analyzed, demonstrating that
      neither can explain somatic metaphors and that an alternative theory is therefore
      needed; and a unitary model of personhood and disease is proposed that avoids
      mind-body dichotomies and dualistic assumptions and lays a groundwork for the
      exploration of physical and subjective aspects of patient reality as playing
      active roles in the development and perpetuation of, and recovery from, any
      physical disease.

PMID- 12518468
TI  - Candace Pert: a molecular Jungian in search of the quantum experiment. Interview
      by Sheldon Lewis.

PMID- 12518469
TI  - Entelechy: the intelligence of the body.

PMID- 12518470
TI  - President's address. Thinking seven generations ahead.

PMID- 12518471
TI  - Conducting a systematic literature review: a brief guide.

PMID- 12518472
TI  - Shielding and being shielded: children's perspectives on coping with their
      mother's cancer and chemotherapy.
AB  - Little research has examined children's perceptions of what it was like when
      their mother was diagnosed and treated with chemotherapy for breast cancer. This
      research aimed to describe the children's perspectives and to suggest
      interventions to assist children to manage the experience with less stress.
      Qualitative naturalistic inquiry methods were used. Purposive sampling was used
      to recruit children whose mothers had chemotherapy for breast cancer in the prior
      two years. Eleven children were interviewed individually or with siblings.
      Children were between seven to 21 years of age. The major theme that emerged was
      Shielding and Being Shielded. Shielding refers to how children protected
      themselves from their thoughts and feelings and protected themselves from others.
      Being Shielded refers to what others did to protect the children. Shielding and
      Being Shielded each had components reflective of knowing/understanding,
      acknowledging/feeling, sharing, and shifting/helping. Recommendations directed
      towards assisting children, parents, and nurses and other health care
      professionals are suggested.

PMID- 12518474
TI  - Mentorship: can it help nursing provide improved cancer care closer to home?

PMID- 12518473
TI  - A national survey of Canadian women: breast health practices, influences, and
      satisfaction.
AB  - In an earlier survey of over 900 women in the local automobile industry, several
      influences and preferences for breast screening were identified. The purpose of
      the current study was to extend the survey population to women across Canada, as
      well as to ascertain women's satisfaction with organized (governmental) screening
      programs within their geographic areas. Using random-digit-dialing, 1,224 women
      25 years and older were interviewed in French or English and their responses
      entered in a CATI system. The interviewers used a modified version of Health Care
      Practices: A Worksite Survey. Results were analyzed by age and geographic region.
      Results indicated support for earlier local findings, as well as high
      satisfaction, but low knowledge and usage of organized breast screening clinics.

PMID- 12518475
TI  - Malignant mesothelioma.

PMID- 12518476
TI  - The Oncology Interactive Education Series.

PMID- 12518477
TI  - [Careers in nursing].

PMID- 12518478
TI  - [Nursing knowledge, nursing education and nursing management. Three student paths
      -one related theme].

PMID- 12518479
TI  - [Something else--but still nursing (interview by Ilona Riebe)].

PMID- 12518480
TI  - [Medication errors can be avoided].

PMID- 12518481
TI  - [Hygiene ground rules for nurses. Shelter and clothing in ambulatory nursing].

PMID- 12518482
TI  - [Observations from the nursing point of view. The new chart of patient rights].

PMID- 12518483
TI  - [Psychiatry: psychiatric nurses find themselves in s college in Great Britain.
      Eleven pilgrims come to the south of Scotland].

PMID- 12518484
TI  - [No employment without training. Including when the training in the certain
      handling of instruments is not prescribed but is nevertheless unequivocally
      necessary].

PMID- 12518485
TI  - [Prevention has no limits].

PMID- 12518486
TI  - A second generation battery-powered toothbrush.

PMID- 12518487
TI  - Laboratory evaluations of two battery-powered toothbrushes and a manual
      toothbrush for efficacy and safety.
AB  - Two laboratory testing procedures, predictive of clinical efficacy and safety,
      have been used to evaluate two battery-powered toothbrushes (a new prototype,
      Crest SpinBrush Pro and a commercially available product, Crest SpinBrush) and a
      standard manual toothbrush (Oral-B Indicator). Interproximal access efficacy
      (IAE) and depth of deposit removal (DDR) have been evaluated in laboratory
      methods using pressure-sensitive paper placed around simulated anterior and
      posterior teeth at a brushing pressure of 250 g with horizontal or vertical
      brushing motions. Twenty-four tests on each toothbrush design were conducted, and
      results were statistically analyzed using ANOVA and the post hoc Tukey test. Both
      of the battery-powered toothbrushes had a significantly (p < 0.001) higher mean
      overall IAE value compared to the Oral-B Indicator product. The Crest SpinBrush
      Pro was significantly statistically higher (p < 0.05) compared to the Crest
      SpinBrush for mean overall IAE (access to interproximal spaces). On overall DDR,
      both of the powered toothbrushes had a significantly (p < 0.05-0.001) lower mean
      overall value compared to the Oral-B Indicator toothbrush (higher mean indicates
      higher irritation potential). Based on these results, both the new prototype
      Crest SpinBrush Pro and the commercially available Crest SpinBrush are predicted
      to be more effective clinically for plaque removal, and at least as safe on hard
      and soft intraoral tissues as the standard manual toothbrush (Oral-B Indicator)
      tested. In addition, the results support that the new prototype Crest SpinBrush
      Pro is more effective than the Crest SpinBrush with respect to IAE and predicted
      plaque removal.

PMID- 12518488
TI  - Plaque removal efficacy of a new experimental battery-powered toothbrush relative
      to two advanced-design manual toothbrushes.
AB  - The current study was designed to assess the plaque removal efficacy of a novel
      experimental powered toothbrush (Crest SpinBrush Pro) compared to two leading
      manual toothbrushes, the Oral-B CrossAction and the Colgate Navigator. In
      addition, this paper reports the results of two additional studies examining the
      relative plaque removal efficacy of the two control manual toothbrushes and a
      number of other manual toothbrushes. The comparative study was a randomized,
      controlled, examiner-blind, nine-period crossover design, conducted among 127
      adult subjects over a two-month period, that examined plaque removal with a new
      battery-powered toothbrush and two advanced-design manual toothbrushes. During
      the course of this study, subjects brushed three times with the experimental
      powered toothbrush and three times with each control manual toothbrush. Study
      participation was on a voluntary basis following written informed consent of the
      subjects. Plaque was scored before and after brushing using the Turesky, et al.
      Modification of the Quigley-Hein Index. Average baseline plaque scores were 2.68
      to 2.69 for the three treatment groups. The experimental toothbrush delivered an
      adjusted (via analysis of covariance) mean difference between baseline and post
      brushing plaque scores (i.e., a plaque removal score) of 0.69, while the control
      toothbrushes delivered adjusted mean differences of 0.46 (Colgate Navigator) and
      0.54 (Oral-B CrossAction). All group differences were statistically significant
      (p < 0.001). The experimental powered toothbrush group had, on average, 49% and
      28% greater plaque removal scores than the Colgate Navigator and Oral-B
      CrossAction groups, respectively. In addition, the Oral-B CrossAction group had,
      on average, a 16% greater plaque removal score than the Colgate Navigator group.
      This result was also statistically significant (p < 0.001). Results on buccal and
      lingual surfaces also demonstrated statistically significantly (p < 0.001)
      greater plaque removal for the experimental battery-powered toothbrush relative
      to the control manual toothbrushes.

PMID- 12518489
TI  - The relative effectiveness of six powered toothbrushes for dental plaque removal.
AB  - During the past three years, a number of new powered toothbrushes have been
      marketed in the United States. The objective of this study was to compare the
      single-use plaque removal efficacy of six powered toothbrushes: a new prototype
      (Crest SpinBrush Pro), Crest SpinBrush, Oral-B Battery, Colgate Motion, Oral-B 3
      D Excel, and a Crest experimental toothbrush design. This study was a randomized,
      controlled, examiner-blind, six-period crossover design, which examined plaque
      removal with six powered toothbrushes following a single use in 26 subjects.
      Plaque was scored before and after brushing for one minute using the Turesky, et
      al. Modification of the Quigley-Hein Index. For statistical comparison, the
      plaque scores were averaged on a per-subject basis. Each subject had a single
      whole-mouth average score for baseline and for the exam following a one-minute
      brushing with their assigned toothbrush. The difference (baseline minus post
      brushing) in average scores was calculated and analyzed using an analysis of
      covariance for a crossover design, with baseline whole-mouth average score as the
      covariate, and terms in the model for subjects, periods, and treatments. Mean
      baseline plaque scores ranged from 1.770-1.897 for the six toothbrush treatment
      groups and were not statistically significantly different. Using the analysis of
      covariance, with respect to all surfaces examined, the new prototype powered
      toothbrush (Crest SpinBrush Pro) delivered an adjusted mean difference between
      baseline and post-brushing plaque scores of 0.544, while the five remaining
      powered toothbrushes delivered an adjusted mean difference of 0.470-0.497. These
      results represent 10-16% greater plaque removal for the new prototype powered
      toothbrush. Overall, the six toothbrushes were not statistically significantly
      different (p = 0.199). However, results of unadjusted pair-wise comparisons
      conducted per the study protocol found that the new prototype powered toothbrush
      removed greater levels of plaque than the Oral-B 3-D Excel, Colgate Motion, and
      Crest experimental toothbrush (p = 0.028, p = 0.038, and p = 0.028,
      respectively). With respect to buccal and lingual surfaces, the new prototype
      powered toothbrush (Crest SpinBrush Pro) delivered very similar results relative
      to the control toothbrushes. Collectively, the results suggest that the new
      prototype powered toothbrush may offer enhanced plaque removal efficiency
      relative to the five other toothbrushes, and be at least as good as the five
      tested powered toothbrushes.

PMID- 12518490
TI  - A study to assess the safety and tolerability of three toothbrushes.
AB  - This study evaluated the oral soft tissue safety and tolerability of an
      experimental powered toothbrush (Crest SpinBrush Pro) compared to two leading
      manual toothbrushes: an advanced-design manual toothbrush (Oral-B CrossAction)
      and a flat-trimmed toothbrush (Oral-B 40 Indicator). Manual brushes are generally
      viewed as safe for use, and as such are appropriate controls. A total of 140
      subjects was enrolled in this single-center, randomized, examiner-blind parallel
      study over a four-week test period. Subjects were instructed to brush in their
      normal manner, twice per day for 60 seconds per use. An oral soft tissue
      interview and examination were conducted by a trained dentist examiner at
      baseline, as well as three days and four weeks after baseline to assess clinical
      signs and symptoms of oral irritation associated with use of the toothbrushes.
      Overall, there were 19 adverse events reported for 18 subjects (13% of the
      population). The adverse events were distributed across test groups with five
      subjects in the experimental powered brush group, eight in the advanced design
      manual toothbrush group and five in the flat-trimmed toothbrush group
      experiencing at least one adverse event. The most frequently reported adverse
      event was localized irritation/inflammation of the gingiva. All adverse events
      were mild in severity except for one report of severe hyperesthesia (tooth
      sensitivity) in the advanced-design manual toothbrush group. There were no
      statistically significant differences between the groups for the proportion of
      subjects reporting adverse events at either three days or four weeks of product
      use. The results of this study indicate that daily use with the Crest SpinBrush
      Pro powered toothbrush is at least as safe as two leading manual toothbrushes.

PMID- 12518491
TI  - The reduction of gingivitis using battery-powered toothbrushes over a one-month
      period.
AB  - This study measured the ability of two powered toothbrushes (Crest SpinBrush and
      Crest SpinBrush Pro) to reduce gingivitis relative to baseline levels over a one
      month period. This study made use of a randomized, controlled, examiner-blind,
      parallel design. Subjects were examined for Loe-Silness GI scores at baseline and
      at one month. The primary efficacy variable was GI score change at one month from
      the baseline GI score. Within-group comparisons to baseline were performed using
      paired t-tests. Secondarily, treatment group differences were examined using an
      analysis of covariance model, with baseline as the covariate. Separate analyses
      were performed for Loe-Silness GI scores and for the number of gingival bleeding
      sites. All comparisons were two-sided and used the 0.05 level of significance. A
      total of 87 subjects completed the study. Of these, there were 57 females and 30
      males, ranging in age from 18 to 70 years with a mean age of 33.1 years. Baseline
      GI scores were 0.487 and 0.449 for the Crest SpinBrush and Crest SpinBrush Pro,
      respectively, and were not statistically significantly different. Both brushes
      demonstrated highly statistically significant reductions in GI vs. baseline (all
      p < 0.001), and delivered an approximately 60% reduction in GI. Baseline bleeding
      site scores were 37.6 and 34.4 for the Crest SpinBrush and Crest SpinBrush Pro,
      respectively, and were not statistically significantly different. Both brushes
      demonstrated highly statistically significant reductions in bleeding vs. baseline
      (all p < 0.001), and delivered an approximately 60% reduction in bleeding sites.
      None of the ANCOVA comparisons between brush groups were statistically
      significant (all p > or = 0.354). Both the Crest SpinBrush Pro and Crest
      SpinBrush powered toothbrushes were highly effective at reducing gingivitis when
      used per manufacturer's instructions.

PMID- 12518492
TI  - The relative cleaning effectiveness of manual and powered toothbrushes.
AB  - Recently, a number of new low-cost powered toothbrushes have been marketed
      globally. Assessment of their cleaning capability in vitro is now becoming
      manageable with novel configurations of new brushing machines, which allow for
      the conventional brushing action and added device action. In this study, the in
      vitro stain removal efficiency of two marketed powered toothbrushes (Crest
      SpinBrush and Dr. Best Battery), a new prototype (Crest SpinBrush Pro) and two
      manual toothbrushes (Oral-B Indicator Soft and Oral-B CrossAction) was evaluated
      using a different brushing technique as a modification of the laboratory testing
      method developed by Stookey and associates at Indiana University Oral Health
      Research Institute. This was a randomized, parallel-group design study that
      examined stain removal with a novel toothbrushing configuration adapted for
      powered and manual toothbrushes. Stain was scored before and after brushing for
      two consecutive one-minute periods using digital image analysis. The mean change
      in L* was statistically compared among toothbrushes with analysis of covariance.
      The mean baseline stain scores ranged from 36.3-40.2 for the five toothbrush
      treatment groups. There was statistically significant evidence of imbalance with
      respect to baseline mean L* (p = 0.006), ranging from 36.3 for the CrossAction
      brush to 40.2 for the Crest SpinBrush Pro. Baseline stain imbalance was addressed
      with the ANCOVA statistical model which adjusts for baseline L*, effectively
      comparing all treatments at the same baseline stain level. Baseline L* was not
      statistically significant (p > 0.1) in the ANCOVA model at one or two minutes.
      With respect to all surfaces examined, the new prototype powered toothbrush
      (Crest SpinBrush Pro) delivered an adjusted (via analysis of covariance) mean L*
      reduction of 14.4 and 22.0 at the end of the first and second brushing periods,
      respectively, while the four remaining toothbrushes delivered adjusted mean L*
      reductions ranging from 5.6-8.6 and 9.4-13.3 at the end of the first and second
      brushing periods, respectively. These results represent 67-157% for the first
      brushing period, and 65-134% for the second brushing period greater stain removal
      for the new prototype powered toothbrush. Overall, the new prototype powered
      toothbrush had statistically significantly greater stain removal (p < 0.001) than
      all other toothbrushes tested. The results, using this powered toothbrush
      compatible brushing machine configuration, show that the new prototype powered
      toothbrush (Crest SpinBrush Pro) produced statistically significantly enhanced
      stain removal efficiency relative to the four other toothbrushes, including Crest
      SpinBrush and Dr. Best powered toothbrushes. The newly configured brushing
      machine delivered a robust method for separating statistically significant in
      vitro differences for the complex cleaning action of powered toothbrushes.

PMID- 12518493
TI  - The effectiveness of two different battery-powered toothbrushes on whitening
      through removal of stain.
AB  - Whitening dentifrices have recently become popular, achieving a whitening benefit
      by surface chemical action and/or abrasion that serve to remove extrinsic stains
      and/or prevent extrinsic stain buildup. Some powered toothbrushes have also been
      demonstrated to have whitening/stain-removal efficacy when used with standard
      dentifrice products. The objective of this study was to evaluate the
      effectiveness of an experimental prototype powered toothbrush (Crest SpinBrush
      Pro) and a commercially available powered toothbrush (Crest SpinBrush) on dental
      whitening through the removal of extrinsic stain. This study was a randomized,
      controlled, examiner-blind, parallel-group design, which examined extrinsic stain
      removal over four weeks of brushing by 70 subjects. Following a three-week period
      of stain induction using rinses of chlorhexidine and tea, subjects were
      randomized to use one of the two toothbrushes. Tooth stain was scored using the
      Lobene stain index at baseline, and after two and four weeks of toothbrush use.
      Prior to statistical analysis, the stain scores were averaged on a per-subject
      basis. The stain reductions (baseline minus post-treatment) in average scores
      were calculated and analyzed using an analysis of covariance, with baseline
      average score as the covariate. The experimental prototype powered toothbrush
      (Crest SpinBrush Pro) delivered statistically significant (p < 0.001) adjusted
      (via analysis of covariance) mean reductions from baseline in Lobene composite
      stain scores of 1.90 and 2.11 after 2 weeks and 4 weeks of use, respectively.
      These results represent 56-62% reductions in extrinsic stain compared to
      baseline. The commercially available powered toothbrush (Crest SpinBrush) also
      delivered statistically significant (p < 0.001) adjusted (via analysis of
      covariance) mean reductions from baseline in Lobene composite stain scores, with
      magnitudes of 1.95 and 2.22 after two and four weeks of use, respectively. These
      results represent 60-68% reductions in extrinsic stain compared to baseline. In
      conclusion, both the experimental prototype powered toothbrush and the
      commercially available powered toothbrush were effective in removing extrinsic
      tooth stain.

PMID- 12518494
TI  - Clinical study to compare two in-office (chairside) whitening systems.
AB  - The objective of this clinical study was to compare the whitening/bleaching
      efficacy of two marketed in-office whitening systems: Discus Dental Zoom!
      Chairside System (25% hydrogen peroxide whitening gel) and Opalescence Xtra Boost
      Kit (38% hydrogen peroxide whitening gel), using the Vita Shade Guide and
      chromameter measurements. The study was an examiner-blind, parallel group,
      randomized and controlled clinical trial conducted in a dental setting. All
      subjects signed a study consent form prior to admission and were given Crest
      Regular Toothpaste and an Oral-B 40 straight-handle toothbrush to use during the
      study. Subjects received a supragingival prophylaxis followed by a screening
      eligibility Vita Shade assessment from which 22 subjects were selected. At
      baseline, all six maxillary anterior teeth were assessed with the Vita Shade
      Guide. Chromameter measurements were taken on either the right maxillary central
      or left maxillary central (tooth No. 8 or tooth No. 9). Subjects were assigned to
      one of two treatment groups, and had three applications of their assigned
      product. Following completion of the treatment phase, and on post-treatment Days
      2 and 7, a visual examination of the condition of the oral soft tissues, together
      with a Vita Shade assessment on maxillary anterior teeth, a chromameter reading
      and a questionnaire regarding tooth sensitivity were completed. At the
      termination of the study, the statistical analysis of the Vita Shade scores
      indicated that both products significantly (p < 0.0001) lightened the color of
      the teeth. The average improvement was between 6 and 9 shade changes.
      Additionally, the Zoom! Chairside System was significantly better than the
      Opalescense Xtra Boost Kit at all time points: post-treatment (p < 0.0001); Day 2
      (p < 0.004); Day 7 (p < 0.003). This difference was between 1 and 2 shade
      changes. The chromameter readings showed a significant difference in the overall
      color change (delta E) to a lighter color for both the Zoom! Chairside System and
      the Opalescence Xtra Boost Kit. Using delta E, the Zoom! Chairside System was
      directionally better than the Opalescense Xtra Boost Kit at Day 2 (p < 0.08), and
      significantly better at Day 7 (p < 0.025). Analysis of the composite parameters
      of delta E (L*, a*, b*) showed that no differences could be detected in the a*
      (redness) parameter. Changes were observed in the L* (brightness) and b* (yellow)
      parameters which paralleled the delta E differences. There were no significant
      differences in induced sensitivity between whitening systems at any time point.

PMID- 12518495
TI  - Evaluation of tapered-end toothbrush bristles regarding efficacy of access to
      occlusal fissures.
AB  - The purpose of this in vitro study was to determine how two toothbrushes, with a
      combination of a tapered-end and round-end bristle design (Group A), compared to
      a conventional toothbrush with only rounded-end bristles (Group B) for cleaning
      in simulated occlusal fissures on a brushing machine. The fissure width at the
      surface was 200 microns, and then tapered down to the fissure base depths of 230
      and 400 microns. The toothbrushes were positioned 90 or 180 degrees to the
      fissure groove surface on the model, and a 200 g force was applied to the brush
      head. The fissure model received 190 strokes over one minute by the brushing
      machine. The removal of an artificial plaque substance in the fissure model was
      measured by a two-dimensional analyzing system. For each combination of the
      fissure depth versus bristle angle versus brush head configuration variables,
      five specimens were measured and means were determined. The results were
      statistically analyzed using a three-way ANOVA followed by Scheffe's test (alpha
      = 0.05). The results demonstrated that the combination of tapered and round-end
      bristles (Group A brush) was statistically significantly (p < 0.01) more
      effective in removing the artificial plaque material on the fissure area than the
      Group B brush for specific types and brush stroke directions.

PMID- 12518496
TI  - Comparison of two dentifrices with respect to efficacy for the control of plaque
      and gingivitis, and with respect to extrinsic tooth staining: a six-month
      clinical study on adults.
AB  - The objective of this six-month, double-blind clinical study, conducted in
      harmony with American Dental Association guidelines, was to provide a comparison
      between Colgate Total Toothpaste and Crest Gum Care Toothpaste with respect to
      their levels of efficacy for the control of supragingival dental plaque and
      gingivitis, and with respect to the levels of tooth staining associated with
      their use. Adult male and female subjects from the Edinburgh, Scotland area were
      entered into the study and stratified into two treatment groups which were
      balanced for age, sex, baseline Quigley-Hein Plaque Index scores and baseline Loe
      Silness Gingival Index scores. Subjects received an oral prophylaxis, and were
      instructed to brush their teeth twice daily (morning and evening) for one minute
      with their assigned dentifrice, using a soft-bristled toothbrush. Examinations
      for plaque, gingivitis and extrinsic tooth staining were conducted after three
      months' and again after six months' use of the study dentifrices. One-hundred and
      nine (109) subjects complied with the protocol and completed the entire six-month
      clinical study. At both the three- and six-month study examinations, the Colgate
      Total Toothpaste group exhibited statistically significantly less plaque,
      gingivitis and extrinsic tooth staining compared to the Crest Gum Care Toothpaste
      group. At the six-month examination, the magnitude of these differences exceeded
      18% for all six parameters measured (18.7% for Plaque Index, 60.5% for Plaque
      Severity Index, 22.2% for Gingival Index, 85.1% for Gingivitis Severity Index,
      45.3% for stain intensity, and 46.3% for stain area). Thus, the results of this
      six-month clinical study support the conclusion that Colgate Total Toothpaste
      provides a statistically significant, substantive advantage in efficacy for the
      control of plaque and gingivitis over Crest Gum Care Toothpaste, while, at the
      same time, providing better control against the development of extrinsic tooth
      staining.

PMID- 12518497
TI  - A comparison of the adhesion of three restorative materials.
AB  - This study compared the adhesion of three different composite restoration resins.
      For this investigation, 45 extracted lower wisdom molars were selected and 45
      Class I cavities were prepared by the same operator, and were randomly divided
      into three groups of 15 samples each. GROUP A: the molars of this group were
      filled with Surefil and the adhesive used was Prime & Bond NT. GROUP B: the
      molars of this group were filled with Prodigy Condensable and the adhesive used
      was Optibond Solo. GROUP C: for the molars of this group, Enamel Plus was used as
      composite and Prime & Bond NT was used as adhesive. As a negative control, twenty
      teeth were used without Class I preparations. Teeth were embedded in cold-cure
      acrylic resin and sectioned longitudinally. Dye penetration at the enamel and
      dentin margins were scored at 30 x magnification. Evaluations were rated from 0
      to 3 (0 = no leakage; 1 = dye penetration up to one-half of the preparation
      depth; 2 = dye penetration more than one-half of preparation depth, but less than
      the axial wall; 3 = dye penetration along the axial wall). All the samples were
      analyzed with SEM at the following magnifications: 80 x (I micrograph), 220 and
      740 x (II micrograph), 1200 x and 4200 x (III micrograph). The samples of Groups
      B and C showed no dye penetration. The samples of Group A showed either a level 2
      or a level 3 dye penetration.

PMID- 12518498
TI  - A clinical methods study of the effects of triclosan dentifrices on gingivitis
      over six months.
AB  - The basic design for human clinical trials which examine prevention of gingivitis
      recurrence is well known. However, the anti-gingivitis efficacy of triclosan
      containing dentifrices has not been routinely demonstrated using this design,
      regardless of formulation. In an effort to better understand the subtleties of
      design which show triclosan efficacy, a study was undertaken to prospectively
      test how subjects with a range of baseline disease levels (which encompassed the
      range of gingivitis severity documented in the triclosan literature) benefit from
      a triclosan dentifrice. This trial was a randomized, double-blind, parallel
      group, six-month study where subjects brushed twice daily with either
      triclosan/pyrophosphate, triclosan/copolymer, triclosan placebo or sodium
      fluoride control (NaF) dentifrice following a prophylaxis. Both gingivitis and
      bleeding were measured using the Loe-Silness Gingival Index (GI) and plaque was
      measured using the Turesky Plaque Index. Comparisons between treatments were
      performed using an analysis of covariance. At month 3, the
      triclosan/pyrophosphate group had a relative mean plaque benefit of 14.4% versus
      the triclosan placebo group (with an associated p-value of 0.004), and subjects
      using triclosan/copolymer had a mean reduction in GI bleeding sites of 16.2%
      relative to those brushing with the NaF control (with an associated p-value of
      0.031). The overall results did not demonstrate a treatment effect for gingivitis
      or plaque for either triclosan-containing dentifrice at month 6. There was
      evidence of modest anti-gingivitis efficacy in the triclosan placebo. In an
      effort to better understand how baseline disease severity may have impacted the
      trial outcome, additional analyses were performed to investigate whether the
      magnitude of a triclosan effect was related to baseline gingivitis levels. An
      analysis of covariance model incorporating a baseline group interaction effect
      indicated that the magnitude of the treatment differences depended on the
      baseline scores The effect was most pronounced for GI bleeding sites. Further
      analysis showed that differences between triclosan dentifrices and the NaF
      control dentifrice were only present for subjects with more than 33 to 63
      bleeding sites, depending on the specific comparison. These findings were
      illustrated through a series of subset analyses on subjects with > or = 20
      (entire study population), > or = 31, > or = 40 and > or = 45 baseline GI
      bleeding sites. The magnitude of the treatment effect for both GI and GI bleeding
      sites increased with each succeeding subset. Unlike that required for other
      antimicrobial agents used in oral care products, these findings suggest that a
      study design which includes subjects with more severe gingivitis at baseline has
      the required sensitivity to demonstrate treatment benefits for triclosan
      dentifrices.

PMID- 12518499
TI  - Laboratory evaluations of elmex inter X toothbrushes for interproximal access
      efficacy and posterior tooth surface cleaning.
AB  - Laboratory methods have been developed to evaluate the ability of toothbrush
      bristles to remove artificial plaque deposits at interproximal sites
      (Interproximal Access Efficacy; IAE) and on distal tooth surfaces (Posterior
      Tooth Surface Cleaning; PTSC). In the testing performed for this study, six
      toothbrushes were evaluated. These were: elmex inter X Sensitive; elmex inter X
      Sensitive Short Head; elmex inter X medium; elmex inter X Medium Short Head; Oral
      B Cross Action 40 medium; and the ADA reference standard toothbrush. Six
      toothbrushes of each design were tested four times under wet brushing conditions
      in all assays. In the IAE studies, toothbrushing was conducted using a vertical
      or horizontal brushing motion, simulated anterior or posterior teeth, and a
      brushing weight of 250 g. The bristles were placed at a 90 degree angle to the
      tooth surface, and brushing was performed for 15 seconds at two strokes per
      second with 50 mm strokes. IAE was recorded as the maximum width of simulated
      plaque deposit removed. For the PTSC evaluations, a horizontal brushing motion
      was used on posterior tooth shapes, with a 250 g brushing pressure for ten
      seconds. PTSC was determined as the maximum measurement of artificial plaque
      deposit removed from the mid-facial area to the maximum post-distal area of the
      most posterior simulated tooth shape. All data were assessed with ANOVA and the
      post hoc Tukey test. In the individual IAE tests, with vertical or horizontal
      brushing on anterior and posterior simulated teeth, and on overall IAE mean
      values, the four elmex inter X toothbrushes were significantly higher (p < 0.01
      0.001) than the ADA reference standard and the Oral-B Cross Action 40
      toothbrushes. The mean PTSC values for all toothbrushes were significantly higher
      (p < 0.01-0.001) compared to the ADA Reference Standard toothbrush mean PTSC. All
      elmex inter X brushes were statistically significantly higher (p < 0.01-0.001)
      compared to the Oral-B Cross Action 40 product. The elmex inter X Medium had a
      significantly higher (p < 0.05-0.001) PTSC compared to the PTSC mean values of
      the other elmex inter X products tested.

PMID- 12518500
TI  - A new fluoride-releasing rubber cup for professional oral hygiene.
AB  - Rubber cups in combination with prophylaxis pastes are commonly used for
      supragingival professional tooth cleaning. This procedure requires frequent
      interruption in order to collect fresh paste. Moreover, the paste-saliva slurry
      blurs the visibility, which implies intermittent rinsing to look for residual
      discolorations. Hawe Neos Dental (Bioggio, Switzerland) has developed a new
      prophylaxis cup aimed at cleaning and smoothing the tooth surfaces, while
      simultaneously fluoridating the enamel without a prophylaxis paste. This new
      prophylaxis cup was tested with respect to cleaning efficiency, resulting surface
      roughness, abrasivity, and the promotion of fluoride uptake into enamel. After 15
      seconds of use, the new cup showed a cleaning efficiency which was 20 to 30%
      higher than that of a conventional rubber cup (p < 0.01) used with the
      prophylaxis pastes Nupro coarse or Hawe cleanic (78% vs. 57 and 49%). The
      fluoride cup had a smoothing effect on the enamel surface comparable to that
      effected by the two prophylaxis pastes. The abrasivity on enamel was lowest with
      the new cup. On dentin, abrasivity was comparable to Nupro coarse, but higher
      than with Hawe cleanic. The fluoride cup also produced a higher amount of KOH
      soluble fluoride on the enamel surface when compared to Hawe cleanic. With
      respect to the structurally bound fluoride, no difference was found. The newly
      developed fluoride releasing Hawe Neos cup represents an effective alternative to
      conventional procedures for supragingival professional tooth cleaning on enamel.

PMID- 12518501
TI  - Instrument processing with an eye on safety. Tips for preventing injuries &
      exposures.

PMID- 12518502
TI  - The chain of cross-contamination: link-by-link.
AB  - Conscious efforts must be made to break the chain of cross-contamination--link-by
      link. Pay attention to detail Avoid being careless Avoid touching objects while
      wearing soiled gloves Frequently wash hands (15-second hand washing) to remove
      pathogens--before and after gloving, and before handling food or drink Wear all
      PPE, and change accordingly.

PMID- 12518503
TI  - Health hazards posed by exposure to latex.

PMID- 12518504
TI  - The Army goes rolling along....

PMID- 12518505
TI  - Pathways to a dental assisting career.

PMID- 12518506
TI  - The role of research institutions in seed-related disaster relief: Seeds of Hope
      experiences in Rwanda.
AB  - The article describes the efforts of a coalition of agricultural research
      centres, Seeds of Hope (SOH) in the rebuilding, of Rwanda, after the genocide and
      war of 1994. Research involvement in emergency relief and rehabilitation was
      unusual at the time and SOH had to forge its unique complementary role. Focusing
      on crop and variety development and conservation it: provided technical advice to
      relief agencies on seed procurement; used its baseline ken to assess the effects
      of war on seed diversity and seed security; made preparations to restore specific
      germplasm (which, fortunately, proved unnecessary) and spent substantial effort
      on rebuilding human resource capacity in research as well as basic scientific
      facilities. The involvement of SOH highlighted the critical, yet very different,
      roles for research during emergency versus rehabilitation periods and
      demonstrated the cost effectiveness of building in a diagnostic component--before
      massive seed or germplasm distributions are programmed.

PMID- 12518507
TI  - The need to look beyond the production and provision of relief seed: experiences
      from southern Sudan.
AB  - Free distribution of seeds in selected areas of southern Sudan has been
      widespread as a way of increasing food security. Field research in areas targeted
      for seed relief found that farmer seed systems continue to meet the crop and
      varietal needs of farmers even following the 1998 famine. Donor investments in
      seed multiplication of improved sorghum have not been sustained due to a lack of
      effective demand for the improved seed beyond that created by the relief
      agencies. The article argues that rather than imposing outside solutions, whether
      through seed provisioning or seed production enterprises, greater attention needs
      to be given to building on the strengths of existing farmer systems and designing
      interventions to alleviate the weaknesses. The case is made to support
      dynamically the process of farmer experimentation through the informed
      introduction of new crops and varieties that can potentially reinforce the
      strength and diversity of local cropping systems.

PMID- 12518508
TI  - Getting of the seeds-and-tools treadmill with CRS seed vouchers and fairs.
AB  - The free distribution of seeds and tools is the standard approach to agricultural
      recovery. The predominance of this approach is partly attributable to the: (1)
      perception that farmer seed quality is poor, (2) insistence on seed
      certification, (3) promotion of researcher varieties, (4) misdiagnosis of
      unavailability, (5) difficulty accessing farmer seed, and (6) support for the
      commercial seed sector. This paper presents a Seed Security Assessment Framework
      to distinguish among the causes of seed insecurity and focuses on three principal
      concepts: seed availability; access to seed; and factors associated with seed
      utilisation. Using this diagnostic framework, Catholic Relief Services (CRS) has
      developed a better approach to promoting seed system-based agricultural recovery.
      It involves a combination of seed voucher distribution and the organization of
      seed fairs, which bring together a range of sellers from whom the holders of
      vouchers may purchase seed. This approach is advantageous because it: strengthens
      farmer seed procurement systems; is cost efficient; in economic terms, has a
      multiplier effect in the community; is straightforward to plan and implement;
      allows commercial sector participation; provides an opportunity to promote
      improved varieties for farmer evaluation; brings together different communities.

PMID- 12518509
TI  - Emergency seed aid in Kenya: some case study insights on lessons learned during
      the 1990s.
AB  - This article reviews the effectiveness of seed-aid distributions in Kenya during
      the 1990s. It analyses the internal process and effects, i.e. the performance of
      the aid itself as well as the external process and effects, i.e. how seed-aid
      intervention affected farmers' broader agricultural management strategies. During
      the drought emergency of 1997, Kenyan farmers favourably judged many of the
      immediate seed-aid features such as crop and variety appropriateness and seed
      quality--even through the overarching goals of the seed assistance were muddled,
      ranging from assistance to the poor, to generalised gift-giving to stimulating
      progressive farming practice. However, the longer term analyses, drawn from
      recollections of a decade of relief activity, showed no concrete evidence that
      seed aid, per se, had strengthened their farming systems, nor that those who have
      received it once were less likely to receive it again. Thus, while seed aid has
      been promoted to lessen the effects of an 'acute' stress, drought, Kenyan
      farmers, in practice, have been experiencing much wider, 'chronic' seed system
      problems. This article ends by exploring this distinction between acute and
      chronic seed system stress and suggests a range of interventions appropriate to
      each.

PMID- 12518510
TI  - Do farmers need relief seed? A methodology for assessing seed systems.
AB  - This article outlines a methodology to help agencies better determine whether or
      not relief seed is needed by farmers affected by disaster. A brief review of
      current seed needs assessment procedures in southern Somalia and Mozambique
      illustrates problems of knowing which crops and households are affected, the
      importance of seed access (not just availability) and the need to plan
      interventions earlier than at present. The development of a Seed Systems Profile
      (SSP) is proposed to understand better both the socio-economic and agro
      ecological aspects of farmers' seed systems. A five-step framework for assessing
      seed systems in disaster situations is also presented. These tools are currently
      being tested and further refined in Mozambique. A better understanding of
      farmers' seed systems will allow for the development of relief and rehabilitation
      interventions that effectively enhance the resilience and reduce the
      vulnerability of these systems.

PMID- 12518511
TI  - Seeds and rights: new approaches to post-war agricultural rehabilitation in
      Sierra Leone.
AB  - Based on preliminary findings of ongoing 'action research' in the war zone in
      central Sierra Leone, this paper shows how more equitable seed distribution could
      contribute to fostering a culture of human rights as well as to agricultural
      rehabilitation. Assessment of seeds-and-toosl programmes in 19 villages found
      that aid agency targeting and distribution modalities channelled inputs through
      village committees which denied assistance to intended beneficiary groups. Such
      distribution inequalities constitute violations of fundamental human rights,
      exacerbate grievance and division and maintain the threat of social disorder. The
      benefits and disadvantages of an alternative, more inclusive, rights-based
      approach to seed distribution are discussed, and preliminary results from the
      pilot phase of CARE's Rights-based Approach to Food Security Project are
      presented. Under this project, village-level peace and rights days are held to
      allow villagers to debate the vulnerabilities that facilitated the war and to
      elaborate on local notions of human rights. In symbolising new beginnings, seed
      can be seen as a useful medium through which to debate a more inclusive--and
      ultimately less vulnerable--society.

PMID- 12518512
TI  - Emergency relief, crop diversification and institution building: the case of
      sesame in The Gambia.
AB  - This article examines the case of the Catholic Relief Service's (CRS) sesame
      support programme in The Gambia which has spanned more than 25 years. It outlines
      the transformation process from relief to development and the role that the
      production of an agricultural commodity, sesame, has played as a key building
      block. Following the drought of the 1980s, concerns to move away from dependence
      on food aid first led to agronomic trials of imported oilseed, then to the
      selection and dissemination of improved sesame varieties accompanied by an
      elaborate and costly support programme. This gradually developed into a long-term
      development-oriented intervention, paving the way for the development of a
      national women's farmers' organisation. The paper provides a case study of an
      intervention that has gone beyond the provision of seed to address agronomic
      research and extension, policy, marketing and institutional issues necessary for
      successful crop diversification.

PMID- 12518513
TI  - [Eye complaints indicative of a tumor elsewhere in the body].
AB  - A variety of clinical presentations of malignant tumour metastases outside of the
      eye and orbit, were seen in four patients: a 52-year-old man who was scheduled to
      have a surgical removal of an oesophageal carcinoma and who presented with
      retinal detachment, a 58-year-old woman in whom retinopathy was the first sign of
      a cervical carcinoma (cancer-associated retinopathy), a 71-year-old man who had
      been treated for colon carcinoma and who presented with an orbital mass, and
      finally a 67-year-old woman with an orbital mass as the first sign of a Grawitz
      tumour. Metastasis should be considered in patients with a history of malignancy,
      who present with ophthalmologic complaints. Further it should be borne in mind
      that eye problems can be the first sign of oncological disease outside the eye.

PMID- 12518514
TI  - [The agent used to free the hostages in Moscow and the insufficient Dutch
      preparations in case of a terrorist chemical disaster].
AB  - In its attempt to liberate the hostages in Moscow, the government used a gas or
      vapour. Classical war gases are not appropriate for such a task because they
      cause irreparable damage, while inhalation anaesthetics are inappropriate because
      they take too long to take effect, and because hundreds of litres would have been
      required for a sufficient effect. Following the liberation of the hostages, it
      was reported that a fentanyl derivative had been used, most likely carfentanyl.
      From the way that the hostages, in Moscow were liberated, it is clear that
      terrorist attacks in which chemicals are used may also take place in the future
      in the Netherlands. In order to be able to react adequately to such situations,
      additional training for physicians and other health-care personnel is urgently
      necessary and the hospitals must also be better prepared for this task,
      especially for the artificial respiration of large numbers of patients and for
      the administration of large amounts of antidote in easy-to-use dosage units. From
      now on, on-site treatment and stabilisation will not be reserved only for trauma
      cases.

PMID- 12518515
TI  - [Outbreaks of viral gastroenteritis, in particular due to the Norwalk virus: an
      underestimated problem].
AB  - In the Netherlands about 4 million people (283/1000) suffer from gastroenteritis
      every year, of which 500,000 cases are caused by 'Norwalk-like viruses' (NLVs),
      formerly known as 'small round-structured viruses'. The reports of two outbreaks
      illustrate the difficulties in determining the cause and source of the infection.
      The course is usually mild, but complications may be serious and ought to be
      documented. Vomiting and diarrhoea are the prominent signs and dehydration is the
      most common complication. Strict hygiene is warranted to prevent spreading of the
      disease. NLVs are highly infectious, notably via the faecal-oral route or by
      aerosols generated by vomiting. Fecally contaminated seafood and other food
      components that are not heated are an important source of infection, the main
      vehicle being sewage water. The microbiological quality control of food is often
      still based on bacteriological contamination, and therefore viral contamination
      may remain unnoticed. Reverse transcriptase PCR is a recent diagnostic tool.

PMID- 12518516
TI  - [Complications following liposuction].
AB  - Liposuction is one of those interventions without a medical indication that are
      usually performed in private clinics. The control over these clinics is regulated
      by the government. The control of specialists who are members of a scientific
      society is the responsibility of the society in question. Liposuction can be
      fatal and a number of serious complications are known to occur, but the frequency
      is unknown. The physician should discuss these possible consequences with the
      patient before the intervention, and adequate aftercare if complications occur
      must be provided.

PMID- 12518517
TI  - [Inducing tolerance against antigens through initial contact via the mucous
      membrane].
AB  - Mucosal tolerance arises in response to protein antigens that enter through the
      mucous membranes. This tolerance is unusual in that it becomes systemic and also
      arises when these antigens subsequently enter the body through the skin or via
      the bloodstream. Clinical applications of mucosal tolerance are hampered because
      induction of tolerance does not appear to be possible once systemic sensitisation
      has taken place. Research into the immunological mechanisms which underlie
      tolerance induction indicates marked local differences in antigen presentation
      and the formation of special classes of T lymphocytes which regulate immune
      reactions. In the future, this knowledge could lead to the application of
      tolerance in the selective therapeutic down-regulation of immunological diseases
      such as allergies and autoimmune diseases.

PMID- 12518518
TI  - [The Dutch Pediatric Surveillance System; a quality focused instrument for
      prevention and research].
AB  - The Dutch Paediatric Surveillance System was initiated by the Dutch Paediatric
      Society and is housed within the TNO Prevention and Health office. The purpose of
      the surveillance system is (a) to gain insight on a population level into the
      prevalence of rare and new diseases in youths (0-18 year), and (b) to promote
      scientific research addressing the background, nature and prognosis, as well as
      the treatment and prevention, of these diseases. A monthly report card is sent to
      all clinically active paediatricians with maximally 10 diseases under
      surveillance. The response rate is approximately 90%. The information from the
      registration can lead to primary or secondary prevention (prevention of the
      disease or of its complications, respectively). The system provides information
      for the amelioration of quality of care and for health management and, at the
      same time, acts as an instrument for scientific research.

PMID- 12518519
TI  - [Recommendations for the management of women with an increased genetic risk of
      gynaecological cancer].
AB  - About 5% of all ovarian-cancer cases are caused by a genetic predisposition, in
      particular as a component of the autosomal dominant hereditary breast-ovarian
      cancer syndrome. This syndrome is usually due to germline mutations in the BRCA1-
      or BRCA2-gene. Ovarian and endometrial cancer also occur in families with
      hereditary non-polyposis colorectal cancer (HNPCC). This syndrome is caused by
      germline mutations in DNA mismatch-repair genes. Women at high risk of
      gynaecological cancer based upon familial clustering of disease or a demonstrated
      pathogenic germ-line mutation are candidates for surveillance: annual
      gynaecological examinations, including vaginal echoscopy and serum carcinoma
      antigen CA125 testing. Prophylactic surgery in the form of adnexectomy leads to a
      marked, but not complete, reduction of ovarian-cancer risk in high-risk cases.
      There is insufficient evidence to advise against the use of oral contraceptives
      or hormonal substitution after adnexectomy for healthy women with a genetic
      predisposition to breast cancer. Recommendations for surveillance and prevention
      should only be given after genetic-risk counselling, based on a detailed family
      study and DNA-based diagnosis.

PMID- 12518520
TI  - [Diagnostic image (118). A man suffering from severe abdominal pain. Chronic
      recurrent pancreatitis].
AB  - A 50-year-old man with a history of alcohol abuse had recurring severe epigastric
      pain. He suffered from chronic recurrent pancreatitis; the CT-scan showed a chain
      of-lakes pattern of the pancreatic duct.

PMID- 12518521
TI  - [A gastroenteritis epidemic caused by a Norwalk-like virus after 2 weddings in a
      restaurant; a plea for integral microbiological investigation].
AB  - OBJECTIVE: To elucidate the cause of an epidemic of gastroenteritis amongst the
      guests and waiting staff of two weddings celebrated on the same day in the same
      restaurant. DESIGN: Retrospective and descriptive. METHOD: Following an outbreak
      of gastroenteritis amongst 215 wedding guests and restaurant staff in 1999, the
      Public Health Institute Midden-Limburg, the Netherlands, inventoried the
      demographic and clinical variables and consumed foods by means of a structured
      written interview. Faecal samples and remaining food products were
      bacteriologically examined, and later on faeces were virologically examined for
      the presence of the Norwalk-like virus (NLV). The attack rates and the incidence
      rates of NLV-positive faecal specimens amongst consumers and non-consumers of
      specific food products were calculated, as well as the corresponding relative
      risks with 95% confidence intervals. RESULTS: The overall attack rate was 66%. An
      NLV with the same genotype was found statistically significantly more frequently
      in faecal specimens of ill persons compared with non-ill individuals. Of the 61
      different dishes served, two showed a statistically significant relation with
      being ill. These food products were eaten by 26% of the ill persons. No
      statistically significant association was found between NLV-positive faeces and
      consumption of a specific dish. The index case began having symptoms of
      gastroenteritis at the morning of the wedding party, before food was served. The
      guests of the two wedding parties used the same entrance and toilets. CONCLUSION:
      The epidemic was caused by a single NLV strain. No association could be found
      between the consumption of certain food products and being ill. The NLV epidemic
      was probably caused through direct or indirect contact between wedding guests and
      restaurant personnel. In the case of such reports of gastroenteritis epidemics,
      it is strongly recommended to test faecal, food product and environment samples
      for both bacteria and viruses, with an emphasis on NLV, to ensure early
      diagnosis.

PMID- 12518522
TI  - [Necrotising fasciitis and myositis as serious complications after liposuction].
AB  - Three days after liposuction of the lower abdomen, a 41-year-old woman was
      admitted for toxic shock-like syndrome with necrotising fasciitis and myositis,
      caused by Lancefield-group-A beta-haemolytic streptococci. The patient was
      treated by radical debridement of the skin, subcutis, fasciae and part of the
      pectoral muscle, plus antibiotics. Postoperatively she required artificial
      respiration for respiratory insufficiency. One week after the operation the wound
      was covered by transplantation of autologous skin. The patient survived, but was
      seriously disfigured. Necrotising fasciitis is a progressive soft-tissue
      infection, characterised by widespread necrosis of the superficial and deep
      fascia, often associated with severe systemic toxic reactions. Unless quickly
      recognised and aggressively treated, the course is often fatal. Due to the
      absence of cutaneous findings in the early stages, diagnosis is difficult.
      Important diagnostic aids are routine laboratory tests, contrast-MRI and a
      combination of the finger test and frozen-section biopsy. Treatment consists of
      early radical debridement, broad-spectrum antibiotics and supportive care. In a
      later stage, soft-tissue reconstruction with autografts or artificial skin grafts
      and skin transposition can be performed.

PMID- 12518523
TI  - [An outbreak of vomiting and diarrhea in a nursing home caused by the Norwalk
      like virus: implications of the Dutch law on infectious diseases and new
      diagnostic options].
AB  - Several residents on a psychogeriatric ward developed vomiting and diarrhoea
      within a short time of each other. The causal factor was the highly contagious
      Norwalk-like virus (NLV) with a high rate of infection amongst both residents and
      staff (84%). This virus is the most frequent cause of gastroenteritis in
      institutions. The illness is self-limiting and can be transmitted from person to
      person. In weakened individuals the course can be serious. The virus can be
      detected in faeces with modern molecular-biological techniques (reverse
      transcriptase PCR). The revised law on infectious diseases ('Infectieziektenwet')
      was established in the Netherlands in 1999. This law requires major outbreaks of
      infectious diseases in institutions as described here to be reported to the
      Municipal Health Service. Together with this agency, strategies to prevent
      further spread of the disease can be implemented.

PMID- 12518524
TI  - [The post-whiplash syndrome: don't treat, but unravel].

PMID- 12518525
TI  - [The post-whiplash syndrome: don't treat, but unravel].

PMID- 12518526
TI  - [The post-whiplash syndrome: don't treat, but unravel].

PMID- 12518527
TI  - [The post-whiplash syndrome: don't treat, but unravel].

PMID- 12518528
TI  - [Summary of the practice guideline 'Refraction errors' from the Dutch College of
      General Practitioners].

PMID- 12518529
TI  - [Broader indication for treatment with statins; the 'heart protection study'].

PMID- 12518530
TI  - [Centenary of the Health Council of the Netherlands. IV. Infectious diseases].

PMID- 12518531
TI  - [The DNA test in the diagnosis of Huntington disease].
AB  - Huntington's disease is the most prominent basal ganglion disease. Huntington's
      gene, IT15, in chromosome 4p16.3, has 67 axons with 10,366 bp coding space and
      unstable CAG sequence that codes glutamine on 5' terminal. The molecular-genetic
      analysis of disease determined expansion of nucleotide repeated CAG sequences. In
      large Bosnian family with Huntington's disease specific DNA diagnosis of IT15
      gene mutation is performed, according the wishes of one female member with "high
      genetic risk", that voluntarily accessed to DNA test in order to make plans for
      her own family "without risk" of pathologic gene transmission. A mutation in IT15
      gene (number of CAG tandem repeats 46, size of DNA fragment 165 bp and 245 bp) is
      detected in DNA of her clinically affected brother. But, results of PCR analysis
      of her DNA sample showed 23 CAG tandem repeats (fragment size 180 bp) that
      excluded presence of Huntington's disease. We accentuate importance of DNA test
      in persons with "genetic risk", that are not gene carriers. In that case there
      are able to create own future without fear of pathological gene transmission.

PMID- 12518532
TI  - [Histomorphologic characteristics of osteosarcoma].
AB  - We reviewed the results examinations, made on 16 patients treated for
      osteosarcoma at Orthopaedic end Traumatology Clinic of University Clinical Center
      in Tuzla, over a ten-year period. Clinical aspects were studied using medical
      records (patient, scharts, historyes, radiographs). Quantification of tissue and
      cellular quality structural changes in the focus of bone destruction were done
      using a morphometrical or stereological method. The volume density (Vv) of the
      stroma mass and of the necrotical bone rafters, as well as the numeric density
      (Nv) of cells were determined on the pathohistologic transsections. The results
      suggest that in the bone destruction focus predominate mononuclears and giant
      cells of osteoclast type, and practically there is no osteogenesis reparatory
      cells.

PMID- 12518533
TI  - [Treatment of type 2 diabetes mellitus based on parameters of B-cell functional
      reserve].
AB  - In prospective study we have investigated the results of type 2 diabetes therapy
      selected on base of measuring the endogenous insulin reserves (insulinemia in
      OGTT) and stoutness of the patients (BMI), and on base of evaluating the dominant
      pathogenetic disorder (insulin resistance and/or weakened insulin secretion). The
      investigation included 113 persons with unregulated type 2 diabetes, males and
      females of 35-65 age, having diabetes in period to 20 years, without acute
      metabolic complications and kidney, liver and cardiorespiratory weakness. On base
      of insulin response to stimulation by glucose (alpha index of stimulation) we
      have classified the patients in three groups: I group--index of stimulation > or
      = 2.5; II group--index of stimulation < or = 2.5 > 1.5; III group--index of
      stimulation < 1.5. According to the level of basal insulinemia and BMI we have
      divided the patients of I and II group to two subgroups. After six-month
      treatment by medicaments selected on base of endogenous insulin reserves and BMI,
      the considerable fall has been achieved of medium values of glucose on empty
      stomach, postprandial glucose, HbA1C, triglycerides, HDL-cholesterol (p <
      0.0001), total cholesterol, systolic blood pressure and diastolic blood pressure
      (p < 0.05) in relation to the values of these parameters of metabolic checking
      before the start of therapy. CONCLUSION: Evaluation of pathogenetic disorder
      dominancy on base of measuring the endogenous insulin reserves and BMI is the
      best criterion and the shortest way for selecting the optimum therapy of type 2
      diabetes in every phase.

PMID- 12518534
TI  - [Effect of eradication of Helicobacter pylori infection on endoscopic findings
      and symptoms of gastroesophageal reflux].
AB  - Gastroesophageal reflux disease (GORD) represents an illness which reflects a
      syndrome caused by returning of acid gastric, alkaline pancreatic and bowels
      content into the oesophagus, which is in the stomach, because of the protective
      mechanisms of oesophageal loss. The aim of this study was that this prospective
      study should explain the role of Helicobacter pylori infection in modification of
      GORD, respectively whether the Helicobacter pylori infection acts protectively or
      by deterioration of the disease. According to the settled rules, the inquiry was
      performed as well as the selection of 97 candidates to undergo research in this
      study. Helicobacter pylori infection has been proved by immunoassay in all pts in
      the beginning of this study. Endoscopy has been performed in all pts, the degree
      of gastroesophageal reflux disease by Sawary-Miller was done. The main group
      consisted of 50 candidates in whom the eradication of Helicobacter pylori
      infection was done with triple therapy, pantoprazol + amoxycilin + klaritromicin,
      which was proven by an immunoassay test. Two groups of pts were formed: the main
      one with eradicated Helicobacter infection, and a controlled one with a
      Helicobacter positive infection, which was subject to modification of life style.
      During 12 months, this study consisted of endoscopic evaluations and monthly
      evaluation of pts daily difficulties. The eradication of Helicobacter pylori
      infection acts on the improvement of gastroesophageal disease course by
      improvement of endoscopic findings by Sawary-Miller, and by decreasing daily acid
      symptoms. The eradication of Helicobacter pylori infection in gastroesophageal
      reflux disease does it act at the symptoms such as heartburn, weekly acid
      symptoms and chest pain.

PMID- 12518535
TI  - [Functional ability and parameters of disease activity in rheumatoid arthritis].
AB  - After the pain, the loss of functional ability is the most important sign of
      severity of the disease for patient who suffer from rheumatoid arthritis (RA).
      Our research is based on the correlation between functional disability with other
      parameters which determine the course of a disease, its activity and the level of
      its progression. The sample consists of 40 patients with RA, with mean age 56.67
      + 10.1 and mean disease duration 11.1 + 7.69. We examined functional ability of
      the patient with Health Assessment Questionnaire-HAQ (0-3), pain with Visual
      Analogue Scale-VAS (0-100), duration of disease, acute phase reactant, morning
      stiffness, joint counts (28), Ritchie articulare index, radiographic changes and
      range of motion. Radiographic changes are measured with Short Erosion Scale--SES
      (Score 0-60), and range of motion with Numerical model of range of motion (1-5).
      A stronger correlation of HAQ was found with most of the disease activity
      parameters, but not with acute phaze reactant and the duration of disease. Strong
      correlation of HAQ exists with the number of tender joints (p < 0.001), number of
      swelling joints (p < 0.05), with VAS (p < 0.001), Ritchic articulare index (p <
      0.001), morning stiffness (p < 0.01), range of motion (p < 0.001) and
      radiographic progression (p < 0.01). The received correlations say that duration
      of disease and lab, results do not have an influence on functional ability, but
      the increase of pain, radiographic progression of the disease and the reduction
      of range of motion influence aggravation of functional status. Drugs which lead
      to decrease of pain and radiographic progression, as well as physical therapy
      which increases range of motion will stop functional disability.

PMID- 12518536
TI  - A pilot study of Topiramate (Topamax) in the treatment of tonic-clonic seizures
      of alcohol withdrawal syndromes.
AB  - In this study for the first time in alcohol withdrawal syndrome, the response to
      topiramate was assessed. 12 patients with median age of 49.5 years and median
      body weight of 76.3 kg were treated with topiramate twice daily for up 30 days,
      starting with a dose of 50 mg in the morning and 50 mg in the evening. The
      preliminary findings of this study suggest that topiramate is very effective
      against tonic-clonic seizures in alcohol withdrawal syndrome. No side effects
      were observed. Only two patients had loss of body weight (3-3.5 kg/4 weeks).

PMID- 12518537
TI  - [Thoracoscopy--the method of choice in the determination of a malignancy as the
      cause of pleural effusion of unknown etiology].
AB  - After complete pulmological investigation remains about 20% of all the pleural
      effusions without etiological diagnosis designated as unexplained pleural
      effusions. Thoracoscopy enables further investigation with the final aim-
      establishing of the etiological cause of the unexplained pleural effusions.
      Recently numerous studies demonstrated that the malignancy is the most frequent
      cause of this aforementioned pleural effusions. OBJECTIVE: Descriptive-analytic
      appraisal of validity of thoracoscopy in establishing of malignancy as a cause of
      idiopathic pleural effusions. TASKS: To establish if the malignancy is the most
      frequent cause of unexplained pleural effusions, to establish diagnostic
      thoracoscopic sensitivity and specificity for malignant disease as cause of
      pleural effusions and to establish positive and negative predictive value of
      thoracoscopy for malignancy. PATIENTS AND METHODS: In the period between
      06.11.1984 and 01.02.2002, included in this investigation were all patients with
      pleural effusions of unknown origin who were referred to the Clinic for Thoracic
      Surgery--UCC Sarajevo, for thoracoscopy after less invasive means of diagnosis
      had failed. Investigation had clinical-manipulative, descriptive-analytic and
      retrospective-prospective design. RESULTS: There were 74 patients with the
      pleural effusions of unknown origin. The malignancy was found in 47.3% (35/74)
      patients. Diagnostic sensitivity of the method for malignancy was 89.7% and the
      specificity 100.0%. The positive predictive value of the thoracoscopy for
      malignancy was 100.0% and negative predictive value 89.7%. CONCLUSIONS: The
      malignancy was the most frequent cause of idiopathic pleural effusions.
      Thoracoscopy has high specificity and sensitivity in regard to discovering of
      malignancy as a cause of idiopathic pleural effusions. Undiagnosed malignancy by
      thoracoscopy excludes malignancy as a cause of pleural effusion with high
      security.

PMID- 12518538
TI  - [Early and late complications in patients treated with hysteroscopic surgery].
AB  - In the last couple of years operative hysteroscopy has become a very popular
      surgical method. It provides us with the possibility to visualize the uterine
      cavity and explore it with absolute accuracy. In the majority of world centers,
      it is performed in ambulance. This is a very simple and financially acceptable
      method, for it does not require special pre and post operative treatments. Of
      course, simplicity of the procedure, the result, as well as the possibility of
      complications, depends on the surgeon as well as the preceeding diagnostics. In
      the period from September of 1997, to September of 1998., 320 operative
      hysteroscopies were performed in the Clinic for Gynaecology and Obstetrics in
      Sarajevo. All 320 patients were submitted for infertility. Detailed anamnesis was
      taken for each patient (HSG, diagnostic laparoscopy, operative laparoscopy, IVF).
      Each patient in our program was also subject to transvaginal Color Doppler
      diagnostics before the operation. This form of diagnostics turned out to be
      highly sensitive and highly specific. We used "Stortz" equipment, including an 8
      mm resectoscope and OTV endocamera. Uterine distension was achieved through
      constant flow of "Purisol" solution. Prior to hysteroscope introduction, we
      dilated the cervical tube using Hegar metal dilatator. All patients were in
      general ET anesthesia. We divided complications in two groups: early and late
      complications. Depending on the sort of complication, patients were hospitalized
      from 1 to 7 days. Early complications occurred in 7 patients: unsuccessful
      cervical dilatation--2 patients; uterus perforation--1 patient; uterine bleeding-
      3 patients; intravasation--1 patient. Impossibility to finish the operation was
      also considered a complication: impossibility of septum incision--1 patient;
      incomplete myoma enucleation--1 patient; impossibility to reconstruct womb in the
      whole--1 patient. Late complications are those that appeared 12-24 hours after
      the operation: post-operative bleeding--2 patients; increased body temperature--2
      patients; pain in lower abdomen--4 patients.

PMID- 12518539
TI  - [Netherton syndrome with recurrent herpes of facial skin].
AB  - In this paper the author presents the case of a girl with the typical Netherton's
      syndrome associated with herpes simplex recidivans. There was no relevans family
      history. In the first of life her skin appeared erythrodermic and diagnosis of
      atopic dermatitis was established. The bronchial asthma developed at age of four
      years. Total IgE and number of cosinofiles were elevated. The intradermal tests
      with pollen grass, house dust, eggs and milk were positive. Intradermal tests
      cellular immunity (PPD, Trichophytin) were negative. The number of T cells and B
      cells in the peripheral blood were normal, but NK cells were slightly decreased.
      Once or twice a year she suffers since 5 years of life exacerbation of herpes
      recidivas on her right site of the face. Microscopic examination of hairs
      revealed the typical appearance of trichorrhexis invaginata. Erythroderma
      persisted until the age of 12 years. Since then polycyclic and serpiginous
      lesions appeared.

PMID- 12518540
TI  - [Biology and pathology of prion diseases].
AB  - During the last few decades, intensive research of the nature of causes of
      transmissible spongiform encephalophatics (TSE) have been undertaken. The
      interest in this field of research has risen especially after the outbreak of mad
      cow disease epidemy. According to proposed Prion hypothesis, PSE agents lack
      nucleic acid, with protein as their primary component. Various research has
      detected the presence of Prion genes which code normal cellular Prion proteins.
      Normal and pathogen protein are isomers but of different conformations. It is
      hypothesed that a pathogen protein when in contact with normal protein causes its
      conversion into a pathogen form which leads to disease.

PMID- 12518541
TI  - [Hadron therapy in carcinoma].
AB  - According to some statistics, in the developed countries of west Europe, one in
      three of population will have an encounter with cancer and, only one in eight of
      this will have treated by use a linear accelerator. Conventional accelerator
      based treatments use photon or electron or proton beams collimated to the tumour
      place. However, some tumors are resistant on this therapy, while others have
      complex shapes or are located around vital radiosensitive organs. In those cases
      it is necessary higher radiobiological efficiency and higher precision. New
      generation of hadron therapy accelerators are arming with light ions. This
      therapy is characterized with high precision, in millimeter range over complex
      volumes. That is also good example how particle physics can benefit medical
      treatments.

PMID- 12518542
TI  - [Ten years of medical informatics education at the Medical School in Sarajevo].
AB  - INTRODUCTION: The medical informatics as the separate medical discipline very
      quickly gets developed, both in Bosnia and Herzegovina. In our country, the
      medical informatics is a separate subject the last ten years, regarding to that
      the Medical curriculum at the biomedical faculties in Bosnia and Herzegovina is
      accorded with the project of the education in accordance with Bolonjski
      declaration and the project EURO MEDICINA. This year the Chair for the medical
      informatics of the Medical faculty in Sarajevo celebrates ten years of its
      existence. WORK METHOD: By the descriptive method of the research which
      comprehended the questionnaire about 400 students of the biomedical faculties we
      established the attitudes and opinions of the students of these faculties about
      the adequacy of the contents of the subject the medical informatics, the
      availability of the adoption of the material by the theoretical and practical
      performance of the process of the tuition and the suggestions and the
      recommendations of the students which contents would throw out from the
      curriculum and which new contents include. WORK RESULTS: The research was
      performed by means the separate questionnaire patterns data carriers with the
      defined characteristics for the quality estimation of the performed tuition. The
      total attitude of the questionnaire speaks about dominantly expressed
      satisfaction of the students with the majority of the parameters about the
      quality and the tuition contents which were evaluated during the questionnaire.
      The results are shown tabelararly and graphically, and descriptively is described
      the program of the tuition and the contents of the methodic units, and the system
      of the examination of the students by the method of the "multiple choice".
      CONCLUSION: The education from the medical informatics is based at the concept
      which use the developed countries of the world, and according to the
      recommendations of the working groups of the European and world association of
      the medical informatics. The theoretical and practical tuition performance in the
      wholeness is performed by the help and at the computer, and the final knowledge
      check of the students also is performed at the computer specially by the
      concepted questions set in the basis which encircled nearly 1500 questions
      combinations.

PMID- 12518543
TI  - DoH banks on invisible workforce of 37,000 staff.

PMID- 12518544
TI  - Should nurses ever strike?

PMID- 12518545
TI  - Blazing a trail.

PMID- 12518546
TI  - The impact of the LEO programme.
AB  - Effective leadership is essential if health services are to modernize and provide
      improvements for patients. The Leading an Empowered Organisation programme is
      providing tens of thousands of clinical staff with the tools to achieve these
      goals. This study provides evidence that the programme is empowering clinical
      staff to promote new ways of working, and as a result advances in service
      delivery and patient care are being made. The issue facing clinical leadership
      development is how prepared organisations are to receive the empowered staff once
      they have completed the programme.

PMID- 12518547
TI  - The differential diagnosis of chest pain.
AB  - Chest pain is a frequent complaint of patients seeking urgent medical assistance.
      It is a serious concern for patients and practitioners because of its potentially
      life-threatening implications, and misdiagnosis can be fatal. The shared
      neurologic pathways of thoracic and abdominal visceral organs complicate the
      diagnosis of chest pain. It is vital that patients presenting with chest pain are
      rapidly and skillfully assessed so that the correct working diagnosis can be made
      and appropriate treatment offered.

PMID- 12518548
TI  - What you need to know about ... liver cirrhosis.

PMID- 12518549
TI  - Intravenous therapy.

PMID- 12518550
TI  - Implementing a Chlamydia pilot screening programme.
AB  - Chlamydia trachomatis is the most common, curable bacterial sexually transmitted
      infection in England and Wales. It can have devastating effects in women. Two
      opportunistic screening programmes for sexually active men and women under 25
      years were initiated on the Wirral and in Portsmouth. The results have formed the
      basis for the setting up of a national screening programme over 10 sites in
      England.

PMID- 12518551
TI  - Patient preferences for a single or shared room in a hospice.
AB  - This study considers the preferences of hospice patients in relation to whether
      they would like to stay in a single or a shared bedroom and what factors might
      affect those preferences. It takes note of the circumstances that are likely to
      be found in a hospice in relation to difficult symptoms such as diarrhoea, the
      process of dying and noise from other patients. The findings show that patients
      generally have a preference for single rooms in order to preserve their dignity,
      respect and privacy. It also shows that choice is important and that a number of
      shared rooms will always be required for patients who prefer to have company.

PMID- 12518552
TI  - It's all I ever wanted to do. Interview by Jennifer Taylor.

PMID- 12518553
TI  - Working at the sharp end. Interview by Leona Armstrong.

PMID- 12518554
TI  - A human dynamo.

PMID- 12518555
TI  - National Hospital Discharge Survey: 2000 annual summary with detailed diagnosis
      and procedure data.
AB  - OBJECTIVES: This report presents national estimates for 2000 and selected trend
      data on the use of non-Federal short-stay hospitals in the United States.
      Estimates are provided by demographic characteristics of patients discharged,
      geographic region, ownership and bed size of hospitals, principal expected source
      of payment, conditions diagnosed, and surgical and nonsurgical procedures
      performed. METHODS: The estimates are based on data collected through the
      National Hospital Discharge Survey. The survey has been conducted annually by the
      National Center for Health Statistics since 1965. In 2000, data were collected
      for approximately 313,000 discharges. Of the 481 eligible non-Federal short-stay
      hospitals in the sample, 434 (90 percent) responded to the survey. Measurements
      of hospital use include number and rate of discharges and days of care, and the
      average length of stay. The population estimates used to compute rates were based
      on the 1990 Census. Estimates of first-listed diagnoses, days of care, all-listed
      diagnoses, and all-listed procedures are presented according to their code number
      in the International Classification of Diseases, 9th Revision, Clinical
      Modification (ICD-9-CM). RESULTS: An estimated 31.7 million inpatients were
      discharged from non-Federal short-stay hospitals in 2000. These patients used an
      estimated 155.9 million days of care. Females had 19.2 million discharges
      compared with 12.5 million for males. Fifty-four percent of all discharges under
      age 65 years had a principal expected source of payment from a private source,
      and 22 percent were covered by Medicaid. Discharge rates per 1,000 population
      ranged from 85.4 in the West to 135.5 in the Northeast. The leading discharge
      diagnosis was delivery for patients under age 65 years and heart disease for
      those 65 years of age and over. The rate of discharges with coronary artery
      bypass graft for males was 2.4 times the rate for females, and males had almost
      twice the female rate for discharges with removal of coronary artery obstruction.
      Hospital stays were 1 day or less for 15 percent of women with deliveries in
      2000, compared with 37 percent in 1995.

PMID- 12518556
TI  - Long-term management of asthma in children: effectiveness of inhaled
      corticosteroids compared to other medications.

PMID- 12518557
TI  - Long-term management of asthma in children: safety of inhaled corticosteroids.

PMID- 12518558
TI  - Combination therapy: addition of other long-term-control medications to inhaled
      corticosteroids.

PMID- 12518559
TI  - Use of antibiotics to treat asthma exacerbations.

PMID- 12518560
TI  - Written action plans compared to medical management alone.

PMID- 12518561
TI  - Peak flow-based compared to symptom-based written action plans.

PMID- 12518563
TI  - Family-centered critical care: a practical approach to making it happen.

PMID- 12518562
TI  - Effects of early treatment on the progression of asthma.

PMID- 12518564
TI  - Two lives on the line: a case study in obstetric critical care.

PMID- 12518565
TI  - Family presence during pediatric resuscitation: a focus on staff.

PMID- 12518566
TI  - The SF-36 quality-of-life instrument: updates and strategies for critical care
      research.

PMID- 12518567
TI  - Why families say no to organ donation.

PMID- 12518568
TI  - Using hyperbaric oxygen to treat diabetic foot ulcers: safety and effectiveness.

PMID- 12518569
TI  - Interventions to decrease family anxiety.

PMID- 12518570
TI  - The Synergy Model as a framework for nursing rounds.

PMID- 12518571
TI  - The anatomy of a lawsuit: Part 3.

PMID- 12518572
TI  - Physicians are asking the nurses to irrigate ventriculostomy catheters .

PMID- 12518573
TI  - Understanding and managing anemia in critically ill patients.
AB  - Although anemia is apparently tolerated in most patients, particularly those who
      are relatively healthy, the ICU population must be thought of differently. Anemia
      in the ICU may be due to acute blood loss, phlebotomy, or to the presence of
      inflammatory disease. The anemia in critically ill patients resembles anemia of
      chronic disease, which is believed to result from a poor endogenous
      erythropoietin response or erythropoietin deficiency. The risks of blood
      transfusions are many and ICU patients may not tolerate infusions of older,
      stored blood. Nonetheless, hemoglobin levels at or above 100 g/L may be important
      for oxygen delivery to vital organs, especially in critically ill patients with
      increased oxygen demands. The appropriate transfusion trigger for critically ill
      patients in this setting remains unknown. Blood transfusions in the ICU may not
      improve outcomes, and numerous studies have been published to suggest the
      contrary, that transfusions may actually worsen patients' outcomes in certain ICU
      settings. Recombinant human erythropoietin (rHuEPO, epoetin alfa) has been shown
      to reduce transfusion needs and increase hemoglobin levels in multiple settings
      and now, it appears to also do so in the ICU.

PMID- 12518574
TI  - On the agenda.

PMID- 12518575
TI  - Crisis care.

PMID- 12518576
TI  - Self-harm: look behind the scars.

PMID- 12518577
TI  - Parting words. Interview by Lynne Pearce.

PMID- 12518578
TI  - Are nurses caring a bit too much?

PMID- 12518579
TI  - Get a grip on arthritis.

PMID- 12518580
TI  - Today's lesson: a healthy diet.

PMID- 12518582
TI  - Recruitment problems in intensive care: a solution.
AB  - This article examines the problems associated with recruiting nurses trained in
      intensive care. It discusses the solutions found at a large district general
      hospital intensive care unit (ICU). Nurses were employed as D grades and offered
      an intense training programme by the trust in an attempt to train its own
      intensive care nurses. This, along with early promotion opportunities, could
      provide a solution to recruitment problems in the specialty.

PMID- 12518581
TI  - Nurses' use of evidence in pre-operative fasting.
AB  - BACKGROUND: Ensuring that a patient fasts before an operation is perhaps one of
      the most fundamental pre-operative responsibilities that nurses might perform on
      a daily basis. However, in this article it will be suggested that, despite the
      undisputed body of evidence spanning more than two decades that demonstrates
      appropriate fasting times, nurses still commonly fast patients for too long.
      CONCLUSION: By reviewing the literature on pre-operative fasting and reflecting
      on the evidence base for nursing practice, this article aims to offer
      explanations of why nurses act contrary to evidence which suggests that their
      practice is outdated.

PMID- 12518583
TI  - Corticosteroids: implications for nursing practice.
AB  - Corticosteroids are essential in the management of various inflammatory
      conditions, but their adverse effects can be a problem. The authors describe the
      uses and effects of corticosteroids, and discuss the nursing role in minimising
      problems associated with their use.

PMID- 12518584
TI  - Nursing dynamos.

PMID- 12518585
TI  - General prescribing principles. Choosing a drug: 1.
AB  - Remember... Use no drug 'before its time. Think before recommending alternatives
      to prescription drugs. Conduct a thorough risk/benefit analysis before
      prescribing. Do not be coerced into prescribing a particular drug. Always pratice
      in accordance with professional guidelines.

PMID- 12518586
TI  - There is an increasing emphasis on nurses' need for leisure time.

PMID- 12518587
TI  - A call to employers.

PMID- 12518588
TI  - Trial and error.

PMID- 12518590
TI  - Recruitment and retention. A study in motivation.

PMID- 12518589
TI  - Changing places.

PMID- 12518591
TI  - Survivors' story.

PMID- 12518593
TI  - Managing quality in services. Part 2.

PMID- 12518592
TI  - Leadership in the elderly care home sector.

PMID- 12518594
TI  - Computed tomography of head injury.

PMID- 12518595
TI  - Radiography of the cervical spine in trauma.

PMID- 12518596
TI  - Chest radiography.

PMID- 12518597
TI  - Ultrasonographic imaging of head and neck pathology.

PMID- 12518599
TI  - Making sense of the national sentinel caesarean section audit: an executive
      summary.
AB  - Midwives enjoy the privileged position of being the senior professional at 72%
      births in the UK. It is a logical assumption to make that the quality of
      midwifery care will have an impact on women's experience and outcome. The aim of
      this article is to help midwives make sense of the results of the National
      Sentinel Caesarean Section Audit (for England, Wales and Northern Ireland).

PMID- 12518598
TI  - Folic acid supplements v bread and pasta.

PMID- 12518600
TI  - Three weeks by the seaside--a review of the party conferences.

PMID- 12518601
TI  - 'State your position clearly and briefly'.

PMID- 12518602
TI  - Guidance paper 1a: commercial umbilical cord blood collection.

PMID- 12518603
TI  - Position statement no. 2. Modern matrons in the maternity services.

PMID- 12518604
TI  - Key issues in delivering midwife-led care: data from telephone interviews across
      the UK.
AB  - This paper is the second in a series exploring the issues in midwife-led care. It
      provides details of a small-scale survey of midwife led units in England,
      Scotland and Wales, which was designed to obtain essential information on the
      process of establishing midwife-led units.

PMID- 12518605
TI  - Midwives to take the lead--not leave.

PMID- 12518607
TI  - Ultrasonography response.

PMID- 12518606
TI  - Home birth reflection.

PMID- 12518608
TI  - Breast cancer: patients need to be better informed.

PMID- 12518609
TI  - How can we prevent food poisoning?

PMID- 12518610
TI  - Helping obese patients lose weight.
AB  - Patients who need to lose weight for health reasons require not only realistic
      practical advice, but also continued support in a non-judgemental setting, such
      as nurse-led clinics in primary care settings.

PMID- 12518611
TI  - Tuberculosis: diagnosis and care.
AB  - The recent resurgence of tuberculosis worldwide means it is vital for health
      professionals to be aware of the risks and able to recognise the symptoms.

PMID- 12518612
TI  - Developing the new role of clinical housekeeper in a surgical ward.
AB  - Methicillin-resistant Staphylococcus aureus continues to pose a threat to
      patients admitted to hospital. This paper describes how the role of a clinical
      housekeeper was developed in an acute male surgical ward and how the
      implementation of the role led to better patient care through improvements in
      cleanliness and a subsequent reduction in infections.

PMID- 12518613
TI  - Informing the future: 1. A review of nursing roles and responsibilities in
      community infection control.

PMID- 12518614
TI  - The nature and causes of violent incidents in intensive-care settings.
AB  - Violence in health-care settings is a common occurrence. This paper reports on a
      questionnaire survey to establish the incidence of such events in a critical-care
      environment. Nurses were asked how they had responded to a violent attack,
      whether they felt it was intentional and whether they had made a formal report.
      There are implications for training and reporting systems.

PMID- 12518615
TI  - Reducing the risks of malnutrition by ensuring adequate dietary intake.
AB  - Nurses are responsible for ensuring that patients have a diet rich in nutrients
      and vitamins. This paper discusses factors that can affect an older person's
      nutritional status such as medication and the effects of ageing, describes how to
      recognise malnutrition, and suggests ways of planning care for this client group
      to ensure that they receive an appropriate diet.

PMID- 12518616
TI  - Does cancer nursing education influence patient care planning?
AB  - Specialist post-registration education is available for cancer nurses. But to
      what extent does it help them improve the care that patients receive? A focus
      group-based study of nurses, along with an audit of patient notes, found nurses
      in one trust are reluctant to carry out some aspects of care, even after
      receiving education, which is reflected in documentation and care plans.

PMID- 12518617
TI  - Wound-bed management: key principles for practice.
AB  - Most chronic wounds have become stuck in the late inflammatory phase of wound
      healing. This can be distressing and frustrating for patients who may have lived
      with such a wound for many months. The key to the concept of wound-bed management
      is to prepare the wound so that modern methods of promoting healing can then be
      applied.

PMID- 12518618
TI  - Can quality-of-life measures help in the care of urology patients?
AB  - Measuring a patient's quality of life aims to help practitioners concentrate on
      individuals' needs. But there are disagreements on how quality of life is defined
      and measured. Focusing on men with prostate cancer, this paper considers the
      problems of finding out what patients are really experiencing, and how nurses can
      help improve things.

PMID- 12518619
TI  - Employing a range of methods to meet patient information needs.
AB  - The NHS has moved on from the days when the doctor knew best and chose what to
      tell, or not tell, a patient. Empowerment is the watchword today, and it is
      crucial for nurses to explore all means of providing patients with information,
      from face-to-face interactions, supported by written material, to helping them to
      seek answers via the world wide web.

PMID- 12518620
TI  - Servant leadership.
AB  - The concept of servant leadership involves leading others through collaboration,
      trust and respect and really listening to others' ideas and opinions.

PMID- 12518621
TI  - [Hypoxic pulmonary hypertension].

PMID- 12518622
TI  - [Plasma erythropoietin concentration in lung cancer patients].
AB  - The goal of this study was to evaluate serum level of EPO in 32 men with lung
      cancer (Squamous cell lung cancer N = 11, Adenocarcinoma N = 10, Small cell lung
      cancer N = 11) in relation to the degree of anemia, stage of disease and the
      regimen of anticancer therapy. The control group consisted of 29 men, among whom
      were 15 patients with posthemorrhagic anemia. Blood samples were withdrawn for
      assessment of blood count, serum concentration of EPO, iron, total iron binding
      capacity (TIBC) and ferritin. The assessment of all parameters was repeated after
      3 months of therapy: RESULTS: Patients suffering from lung cancer were
      characterized by a lower hemoglobin level and higher level of EPO as compared
      with the control group. A significant negative correlation was found between
      hemoglobin level and EPO serum concentration in all groups of patients and in the
      control group. The strongest correlation was observed in the control group t = 
      0.812. In each group of patients the serum level of EPO increased after
      treatment; although a significant increase was found only in surgically treated
      patients and patients after chemotherapy. After treatment the correlation between
      hemoglobin and EPO became stronger especially in the group of patients with small
      cell lung cancer. CONCLUSIONS: 1. Patients with lung cancer are characterized by
      inappropriately low serum EPO levels when related to the degree of anemia, 2. The
      suppressive effect of lung cancer on EPO secretion depends on the histological
      type of the cancer (with the exception of small cell lung cancer). 3. The
      increase of EPO level after treatment seems to be caused not only by a decrease
      of hemoglobin concentration, but also by reduction of the tumor mass.

PMID- 12518623
TI  - [Invasive aspergillosis in autopsy material of patients treated at the Institute
      of Tuberculosis and Chest Diseases during the years 1993-2000].
AB  - The aim of this paper is an analysis of clinical documentation and results of
      autopsy of 21 patients (pts) who died of invasive aspergillosis (IA) in the
      Institute of Tuberculosis and Chest Diseases in years 1993-2000 and the
      assessment of predisposing factors for IA. In 17 pts IA was the main and in other
      4 only an accessory cause of death. All pts were treated with corticosteroids
      and/or cytostatic drugs--because of lung cancer (11 pts), cancer in other site (2
      pts), haematologic disorders (2 pts), Wegener's granulomatosis (1 pt),
      polymyositis (1 pt), idiopathic pulmonary fibrosis (1 pt) and other diseases (3
      pts). In 15 out of 21 pts granulocytopenia was revealed (from 0.008 x 10(9)/L to
      0.82 x 10(9)/L) on an average one month before death. In 15 pts IA was limited to
      the lungs, in 6 others there were also fungal lesions in brain, kidneys, liver,
      spleen and heart. Pts with disseminated form of IA had significantly lower
      granulocyte count and were treated with higher doses of corticosteroids than
      others. Immunosuppressive drugs and granulocytopenia can be regarded as
      predisposing factors. Fatal course of IA depended also on the late diagnosis.

PMID- 12518624
TI  - [Evaluation of vascular endothelial growth factor (VEGF) in neoplastic and
      tuberculosis effusions--preliminary results].
AB  - Angiogenesis is an essential process for tumor progression and VEGF is thought to
      be a critical factor for this process. VEGF is also known as a strong capillary
      permeability inducer, what can be important for pleural effusion development. The
      aim of the study was the comparative analysis of VEGF concentration in pleural
      effusions collected from 31 patients with various type of cancer, 8 patients with
      tuberculosis, 5 patients with transudates. Additionally VEGF concentrations in 11
      serum specimens from patients with neoplastic disease was evaluated. VEGF
      concentrations was determined using a sandwich enzyme-linked immunoadsorbent
      assay. The VEGF level in pleural transudates as well as tuberculous effusions was
      significantly lower than in malignant fluid. The were no differences in VEGF
      level in malignant pleural fluid of different origin. The correlation between
      VEGF concentrations in malignant pleural fluid and sera of individual patients
      was not found. Our results indicate that VEGF might play an important role in
      accumulation of pleural fluid especially that of malignant origin. VEGF level in
      pleural fluid differs significantly from cancer to benign group of patients what
      can be important for differential diagnosis of plural effusions origin.

PMID- 12518625
TI  - [The role of high dose rate (HDR) brachytherapy in advanced non-small cell lung
      cancer].
AB  - The aim of this study was to determine the influence of brachytherapy on the
      prognosis in advanced NSCLC, elaboration of clinical criteria useful in patients
      qualification to brachytherapy and the radiation method optimization. Between
      January 1994 and June 1998, 325 patients with symptomatic inoperable
      endobronchial obstructing lung cancer received brachytherapy alone or combined
      with external beam irradiation with palliative or radical intent. Patients were
      given 1 to 4 temporary Ir-192 endobronchial implants at the site of obstruction.
      Implant doses ranged from 6 to 12 Gy specified at a radius of 1 cm from the
      centre of the source. Total implant doses ranged from 6 to 24 Gy. Depending on
      radical or palliative intents external beam irradiation doses ranged from 20 to
      60 Gy. The results were compared with results achieved in control group (N = 191)
      treated exclusively with external beam irradiation. Patients who received
      combined treatment revealed higher frequency of release or disappearance of
      hemoptysis, dysponea and atelectasis. Also the duration of clinical remission was
      significantly longer with combined treatment. In the group treated with radical
      intent higher percentage of patients with total tumor regression in both
      endoscopic and radiologic view was observed after tele--and brachytherapy
      compared with teleradiotherapy alone (respectively 29.8% and 19.4%). The group
      treated with palliative intent brachytherapy alone provided response rates
      comparable to those achieved with external beam irradiation alone or tele and
      brachytherapy. The relative risk of fatal pulmonary haemorrhage (FPH) and
      radiation induced bronchitis (RIB) were higher when NTD > 70 Gy, brachytherapy
      and laser therapy were administered and in patients with lobar bronchus
      infiltration. Knowledge of risk doses of FPA and RIB allow to optimise
      brachytherapy in patients with advanced NSCLC.

PMID- 12518627
TI  - [Transbronchial needle aspiration biopsy in the diagnosis of peripheral lung
      lesions].
AB  - In 1996-2000 in 55 patients (16 females, 39 males) admitted to Department of
      Phtisiopneumonology in Zabrze because of peripheral lung lesions (diameter 2.5
      9.5 cm mean 4.5 cm). The transbronchial aspiration needle biopsy (TANB) was
      performed as diagnostic procedure during fiberoptic bronchoscopy. Subjects
      classified to TANB showed no pathologic changes in the bronchial tree during
      fiberoptic bronchoscopy. In all subjects the TANB was performed using special
      Wang's needles and always under fluoroscopy supervision. Based on pathologic
      examination of specimens obtained by Wang's needle the diagnosis was established
      in 29 (52.7%) cases. The most frequent diagnosis was non small cell carcinoma--in
      22 (40%) of examined patients. The small cell carcinoma was confirmed only in 1
      patient. In 3 (5.5%) patients tuberculosis was diagnosed. TANB was good tolerated
      by almost all patients, only in 1 patient small pneumothorax was recorded and in
      6 cases small bleeding occurred. We conclude that transbronchial aspiration
      needle biopsy is safe and efficient method in diagnosis of peripheral lung
      tumors.

PMID- 12518626
TI  - [Neuron-specific enolase (NSE) serum level as a prognostic factor in non-small
      cell lung cancer].
AB  - The aim of the study was to assess the significance of elevated NSE serum level
      in NSCLC patients for tumor response to chemotherapy and for survival. The NSE
      serum level above 12.5 mg/l was regarded as elevated. We found elevated serum
      level of NSE in 71 of 146 patients (48.6%) at the time of diagnosis of inoperable
      non-small cell lung cancer, independently to age, sex, performance status and
      histological type of cancer. All patients were treated using cisplatin based
      combination chemotherapy. 44 patients were treated with cisplatin/etoposide
      (group PE), 37 with cisplatin/vinblastine (group PV), 20 with
      cisplatin/vinorelbine (group PN) and 58 with cisplatin/etoposide/vinblastine
      (group PEV) combination. In 26.7% partial response and in another 21.2% minimal
      regression were found after chemotherapy. Partial response was observed in 38%
      patients with elevated NSE serum level but only in 16% patients with normal NSE
      serum level and difference was significant (p = 0.0153). Median survival time was
      8.5 months for the whole group with no difference according to serum level of
      NSE. One-year survival rate was 29% and 9 patients survived 24 month or more. We
      conclude that although the tumor in patients with elevated NSE serum levels
      regress more frequently than in others it does not influence their survival.

PMID- 12518628
TI  - [Concentration of nitric oxide in exhaled air in patients with sarcoidosis--pilot
      study].
AB  - Exhaled nitric oxide (eNO) concentration measurement may allow for noninvasive
      estimation of severity of airways inflammation in asthma and other airways
      diseases. The purpose of this study was to evaluate usefulness of eNO
      concentration measurements in patients with pulmonary sarcoidosis. Study group
      consisted of 22 patients with sarcoidosis (8 women, 14 men aged 26-46). They
      included 11 patients with radiographically stage I and II and 11 patients with
      stage III of disease. Sixteen patients had active pulmonary sarcoidosis and 6 had
      nonactive disease. Ten patients had indications for treatment, 12 patients had
      not any. Exhaled NO was measured by means of SIEVERS 280 Nitric Oxide Analyser
      (USA). There was no significant difference in mean eNO concentration in study
      group (6.91 +/- 0.60 ppb) and in normal control (5.2 +/- 0.73 ppb, p = 0.10).
      Exhaled NO concentration was similar in patients with sarcoidosis stage I and II
      (7.5 +/- 1.08 ppb) and in patients with stage III disease (6.2 +/- 0.51 ppb, p =
      0.27). We failed to found significant difference in eNO concentration between
      patients with active (6.7 +/- 0.71 ppb) and nonactive sarcoidosis (7.5 +/- 1.1
      ppb; p = 0.57). Neither did eNO concentration differ between patients with and
      without indications for therapy (5.77 +/- 0.50 ppb vs. 7.8 +/- 0.95 ppb; p =
      0.08). In conclusion our pilot study results indicate that measurement of eNO
      concentrations may be of little value in patients with sarcoidosis.

PMID- 12518629
TI  - [The evolution of threshold values of air conduction in the extended high
      frequency range (9-18 kHz) in patients suffering from the pulmonary tuberculosis
      treated with combination of SM, INH, RFM, and PZA].
AB  - The evolution of threshold values of air conduction in the extended high
      frequency range (9-18 kHz) at patients suffering from the active pulmonary
      tuberculosis treated with the combined therapy (SM, INH, RFM, PZA). There were
      audiologically examined 13 patients (the average age 41.2) suffering from the
      active pulmonary tuberculosis and treated with the combined therapy (SM, INH,
      RFM, PZA). In 13 tuberculosis patients the full range of audiometric tests and
      measurements including: the pure tone audiometry, acoustic impedance and the
      extended high frequency range threshold audiometry (9-18 kHz) have been applied
      before starting the treatment with SM, INH, RMP and PZA and in the two months
      later--after its completion. The reference group was composed of 10
      audiologically healthy individuals (the average age 40.2). A significant hearing
      loss with respect to air conduction within the extended range of high frequencies
      (9-17 kHz) was stated. The said hearing pathology can be diagnosed at earlier
      stages by the use of the extended high frequency range audiometry than through
      applying methods of conventional audiometry.

PMID- 12518630
TI  - [Organizing pneumonia--diagnostic and therapeutic problems].
AB  - Organizing pneumonia (OP) is a well histopathologically defined disease, which
      can be induced by many factors--infections, drugs, connective tissue diseases
      etc. In many cases a rapidly progressive course is observed with clinical picture
      of pneumonia. We report a case of organizing pneumonia with an acute onset and
      rapid deterioration in 58-year-old women. After unsuccessful treatment with
      antibiotics, prompt biopsy of the lung (videothoracoscopy) helped to establish
      the diagnosis. A rapid improvement after corticoid therapy was observed. Low dose
      corticoid treatment is continued. Patients remains well 20 months after onset of
      symptoms.

PMID- 12518631
TI  - [Primary ciliary dyskinesia--Kartagener's syndrome and fertile male].
AB  - Primary ciliary dyskinesia (PCD) is a rare genetic disease, in which a number of
      human organs are involved: upper and lower respiratory tract, spermatozoa in
      males and fallopian tube in females. In minority of cases PCD presents as
      Kartagener's syndrome (KS): sinusitis, bronchiectasis and inversion of internal
      organs. We report a case of Kartagener's syndrome in 43-year-old fertile male.
      After clinical and radiological examination and biopsy of the bronchial mucosa
      diagnosis of KS was established. The problem of fertility in KS males is
      discussed.

PMID- 12518632
TI  - [The quantitative estimation of angiogenesis in lung carcinoma and its prognostic
      significance in the present clinical studies].

PMID- 12518633
TI  - [New aspects of Wegener's granulomatosis pathogenesis].

PMID- 12518634
TI  - [Allergic inflammation and remodeling of airways].

PMID- 12518635
TI  - [Bronchial hyperreactivity in asthma].

PMID- 12518636
TI  - [Monitoring of lung function in obstructive diseases].

PMID- 12518637
TI  - [Immunopathology of bronchial asthma and COPD].

PMID- 12518638
TI  - [Mechanism of COPD exacerbation].

PMID- 12518639
TI  - [Treatment of allergic rhinitis].

PMID- 12518640
TI  - [Inhaled therapy--method of choice in asthma treatment].

PMID- 12518641
TI  - [New cholinergic drugs in asthma and COPD].

PMID- 12518642
TI  - [Specific immunotherapy in patients with allergic rhinitis as a prevention of
      bronchial asthma--myth of reality?].

PMID- 12518643
TI  - [Inflammation mediators in asthma treatment].

PMID- 12518644
TI  - [Leukotriene antagonist drugs].

PMID- 12518645
TI  - [Anti-IgE therapy].

PMID- 12518646
TI  - [Possibilities of allergic inflammation control in patients with bronchial
      asthma].

PMID- 12518647
TI  - [Education program in asthma].

PMID- 12518649
TI  - [COPD methods of treatment--international consensus].

PMID- 12518648
TI  - [Education program in COPD].

PMID- 12518650
TI  - [Difficulties of diagnosing asthma in children].

PMID- 12518651
TI  - [Methods of treatment of children with asthma--international consensus ].

PMID- 12518652
TI  - [Errors in medical practice].
AB  - The frequency of the error in Medicine is not well known but in any case it must
      be quite high. They are several types of errors: related to planning or
      performance, active or latent, and in relation to diagnosis, treatment or
      prevention. The consequences of the errors are potentially serious for both the
      patient and the doctor. The human factor exists in most of the errors, but this
      does mean the doctor is guilty. Lot of circumstances leads to the error which
      could not be avoidable: ambience and organization of the work, type of
      institution and task, and features of the patients. It is very important to
      lessen the numbers of errors in Medicine through registers of errors and research
      based on the system (not centered in the persons) in order to apply corrective
      measures to the system.

PMID- 12518653
TI  - [Bone regeneration in oral surgery].
AB  - Bone regeneration is the technique of choice in order to repair small and medium
      sized bone defects in maxillary. It is used as an auxiliary medical treatment for
      dental implants. In this work, we show the different state of the art techniques
      used in bone lesions repair, and we also show experimental results obtained in
      our research group using bone morphogenetic protein BMP-2. This protein has been
      expressed in an E. Coli strain previously modified with the protein nucleotide
      sequence. We also show a carrier developed in our laboratory that is able to bind
      the rhBMP-2 and to liberate it in its active form. The mechanical properties of
      the carrier can be chemically modified. We have tested Ti implants covered with
      films of this material activated with rhBMP-2. The experimental in vivo results
      obtained with this kind of implants has been impressive.

PMID- 12518654
TI  - [To be born in the 21st century: maternal-fetal perspectives].
AB  - After analyzing the results obtained in 22.239 gestations and assisted
      childbirths between 1997-2000, as well as the observed trends in these
      childbirths, it is obtained data that are valid to predict the most probable
      evolution of a low risk gestation. The ended childbirths happened in 87.3% of
      patients, but only 27% happened in the 40th week. There was 9.9% of pre-ended
      childbirths and only 1.7% post-ended, due to they are induced in the 41st week.
      The prediction of great premature baby continues improving each year, and the
      mortality starting from 1.000 gr. Is similar to others. It is observed the grave
      morbidity in 15%, and with possible sequelas in 6%. The childbirth has been
      iNduced in 13.2%, especially by premature tear of membranes and prevention of
      post-ended childbirth. The incidents of caesaran operation has been 18.57% in
      2001, and forceps 16.7%. This last figure is due to his prophylactic use and the
      high rate of epidural analgesia (61.3% last year). The standard perinatal
      mortality has been 4.2% per 1000 chilbirths, and the hospital mortality 9.72% per
      1000. These facts are useful to answer the questions that pregnant women make
      when the date of delivery is close, patients that use to be more than 30 years
      old in her first gestation, and with tendency to age increase.

PMID- 12518655
TI  - [Deafness and aging: studies in experimental models].
AB  - Since 1970 a progressive aging of the world population, mainly in the most
      developed countries, has been observed. Spain could have, around 2050, the most
      aged human population of the world. Therefore, scientist show an increasing
      interest on the study of the aging-related pathologies (i.e. deafness linked to
      aging process: presbycusis). The deep analysis of the presbycusis physiopathology
      will be based on the study of patients, but also on animal models. This report
      summarizes our results obtained on the analysis of the deafness linked to aging
      on the C57/BL/6 mice.

PMID- 12518656
TI  - [The medical education plans at the Complutense University, Medical School].
AB  - The Medical Education of the Medical Faculty in the Complutense University of
      Madrid is analyzed since its double origin: The Cardinal Cisneros Constitutions,
      January 22-1510 and the Royal Cedula of King Charles III, February 24-1787, in
      which is created the Royal College of Surgery Saint Charles in Madrid. The
      Medical science was divided in independent subjects of study which programs were
      modified by the professors and brought up to date frequently. From 1972 clinical
      training was widen by subscription of agreements with five main hospitals which
      facilities are used and the personal cooperate in medical education. Since 1993
      plan, as in 2000 plan, deep modifications were implemented as an increase of the
      clinical practice which extent was larger than the theory.

PMID- 12518657
TI  - [Neuroprotection by aspirin in cerebrovascular pathology].
AB  - Aspirin reduces the size of infarcts after ischaemic stroke. Although this fact
      has been attributed to its antiplatelet actions, direct neuroprotective effects
      have been also reported. We have demonstrated that aspirin is neuroprotective by
      inhibiting glutamate release in "in vitro" models of brain ischaemia. A
      pharmacological dissection of the components involved, using cell cortical
      culture exposed to oxygen-glucose deprivation, indicated that aspirin selectively
      inhibits the increase in extracellular glutamate concentration which results from
      reversal of the glutamate transporter, a component of release which is due to ATP
      depletion. Moreover, the neuroprotection afforded by aspirin occurred in parallel
      to a lesser decay in ATP levels after OGD. Aspirin not only elevated ATP levels
      in intact cortical neurones, but also in isolated brain mitochondria. On the
      other hand, using a whole-animal model of permanent focal brain ischaemia (MCAO;
      middle cerebral artery occlusion), wed have also demonstrated that aspirin (30
      mg/Kg i.p. administered 2 h before the occlusion) produced a significant
      reduction in infarct volume, effect that correlated with the inhibition caused by
      aspirin on ischaemia-induced increase in brain and serum glutamate concentrations
      after the onset of the ischaemia. Aspirin also inhibited ischaemia-induced
      decrease in brain ATP levels. Finally, clinical studies showed that prior
      treatment with aspirin was associated with a lower risk of neurological
      deterioration after acute ischemic stroke which was related to a reduction of
      glutamate release. Our present findings show a novel mechanism for the
      neuroprotective effects of aspirin, that takes place at concentrations in the
      antiaggregant-analgesic range, useful in the management of patients with risk of
      ischaemic events.

PMID- 12518658
TI  - [A remembrance of Clarin's illnesses in his centenary].
AB  - The Spanish famous writer Leopoldo Alas, also known by the pseudonymous of
      "Clarin" suffered from two main kind of illnesses: nervous and digestives. Both
      began early, when he was only thirty two. At that moment, and during all his
      thirties, nervous ailments were conspicuous, but digestive problems were growing
      up slow but steadily and became the most serious and even menacing during his
      forties. Nervous pathology was double: on the one hand, some attacks of migraine
      with visual disturbances (scotoma), dysphasia and other "indescribable nervous
      oddities", which happened about 4-5 times per year; on the other, several
      emotional and vague symptoms, such as melancholia, dejected mood, anxiety,
      nervousness, etc. Digestive symptomatology, consisting of atonic constipation,
      intestinal dyspepsia, febricula, and a feeling of being "as a blocked drain", is
      due--no doubt--to tuberculous peritonitis diagnosed by his young nephew Dr.
      Martinez. This serious illness was the cause of his death on the 13th June 1901,
      when he was only 49.

PMID- 12518660
TI  - [Present sanitary problems of immigrant women].
AB  - After revising some of the most important migratory phenomenons that have been
      along history, the subject is based on increase of feminine immigration, in the
      same way that in principal responsible causes of the matter. The most important
      sanitary problems are studied. Firstly, the common problems with men: increase of
      tuberculosis, of AIDS, of sexual transmission illness and parasitosis, inside
      transmissible processes, in the same way that psychological processes. Secondly,
      the specific women problems, concerning with the maternity, the delivery, the
      prostitution, and other problems less frequent as the ablation, the lack of
      communication, etc. Equally, possible solutions are expounded, always
      contemplating the three essential aspects: political, social and sanitary
      actions.

PMID- 12518659
TI  - [Microbiology and cystic fibrosis].
AB  - The respiratory infections are the rule in sick persons of cystic fibrosis. After
      the colonization in one's early childhood by Staphylococcus aureus and
      Haemophilus influenzae, it is established the colonization produced by the mucous
      strains of Pseudomonas aeruginosa, the principal etiogenic of this illness, that
      can become to isolate in more than 95% of sick persons at three years old. That's
      why the etiogenic factors of this bacterium are studied, as they are toxins,
      pigments, enzymes, and principally the alginate, hydrocarbonated polymer
      responsible of the mucous substance that covers these characteristic strains of
      cystic fibrosis sick persons. All these components are regulated by a complex
      genome, the biggest until noe sequenced in bacterium, and that explains the
      importance of the microorganism and its natural resistance or acquired to
      environmental alterations and to antibiotics and disinfectants. In the evolution
      of the clinic chart, it can appear others gramnegative bacteriums (among it
      emphasizes Burkholderia cepacia and Stenotrophomonas maltophilia), mycobacterium
      and even fungus; all that would explain the chronification of lung charts and the
      difficulty of these sick persons treatment.

PMID- 12518662
TI  - [Prostate cancer: diagnosis and survival].
AB  - Clinical behaviour of prostate caner is highly variable and difficult to predict
      in the individual patient, but is a generally a slow growing tumor. The modern
      diagnostic tools (prostate specific antigen and ultrasonically guided transrectal
      biopsy of the prostate) allow detection of prostate cancer when it is still
      localized to the gland and thus, potentially curable. Current treatments, surgery
      (radical prostatectomy) and external beam radiotherapy, cause considerable
      morbidity. Considering that many men with a diagnosis of prostate cancer will not
      die from their prostate cancer but with it, currently "most patients are being
      treated in order to save a few". Furthermore, all patients subjected to
      aggressive treatment experiment morbidity from the beginning, hoping to obtain a
      survival benefit after five to ten years. There is an urgent need for new
      treatments with similar efficacy but with reduced morbidity. Ultrasonically
      guided transperineal criosurgery of the prostate is gaining momentum as a
      minimally invasive treatment alternative, that respects patient's quality of life
      and is equally efficacious.

PMID- 12518661
TI  - [The outriggers of personality].
AB  - The authors analyze the self-esteem, their components and his intervention on
      personality protection and the methods that person has to obtain a good self
      esteem. The authors finish marking the strongest support of self-esteem.

PMID- 12518663
TI  - The ethics of research with children.
AB  - In this article, the focus of which is research with children, Peter Allmark
      considers ethical issues in relation to both quantitative and qualitative
      research. Guidelines on the ethical conduct of research with children focus
      primarily on issues to do with quantitative research (e.g. RCPCH 2000). For this
      reason, this article tries to draw out points of particular importance to
      qualitative research. It begins with some assumptions and points of terminology,
      before briefly describing the history of the development of ethical regulation.
      It then discusses specific ethical issues that arise when researching with
      children. These are placed into three main categories: scientific validity,
      welfare, and rights and dignity.

PMID- 12518664
TI  - Interaction as an ethically sensitive subject of research.
AB  - In this paper, Hanna Maijala, Paivi Astedt-Kurki and Eija Paavilainen discuss
      ethically sensitive family nursing research. A study of the interaction between
      caregivers and families expecting a child with an abnormality is used as an
      example: 29 parents and 22 caregivers were interviewed. Complementary data were
      obtained from essays written by five parents. This sensitive subject required
      discretion, especially when the parents were first asked to participate in the
      study, and during subsequent interviews. From the perspective of the data
      analysis, it was essential to obtain the informants' personal experiences
      unaltered. The constant comparative method of grounded theory was used to analyse
      the data. In the study findings, special attention was paid to presenting the
      results truthfully, while safeguarding the informants' anonymity. In conclusion,
      the ethical questions related to the subject of the study are discussed from the
      point of view of both the participant and the researcher.

PMID- 12518665
TI  - Illustrating the ethical dimensions of action research.
AB  - Graham Williamson and Sue Prosser discuss the ethical dimensions of action
      research, informed by their experiences of participation in an action research
      project in the workplace.

PMID- 12518666
TI  - An approach to the phenomenological analysis of data.
AB  - In this paper, Helena Priest describes and justifies a phenomenological research
      method that may be used to explore complex and nebulous concepts relevant to
      nursing and health care, for example, the concept of 'caring'. The history and
      development of Husserlian phenomenology are outlined, followed by an account of
      the use of phenomenology within nursing research. Tensions inherent in the use of
      Husserlian phenomenology in nursing research are noted. A phenomenological
      approach to data analysis, designed to address some of these tensions, is
      described and compared with several well-established phenomenological analysis
      strategies. Issues of reliability, validity and generalisability are discussed,
      as are limitations in the use of the approach, before conclusions relevant to
      healthcare researchers are drawn.

PMID- 12518667
TI  - The final hurdle: preparation for the PhD viva examination.
AB  - The viva examination is the culmination of the PhD process. However, it is
      important to prepare carefully for this final and important hurdle. In this
      paper, Barbara Jack looks at the different stages of the viva examination, which
      include undertaking a careful and systematic preparation. This preparation
      involves gaining a comprehensive awareness of the university procedure for the
      viva, researching examiners, and considering the value of having a mock viva. The
      paper explores the actual viva and makes suggestions to deal effectively with
      questioning from the examiners. Finally, the results of the viva and steps needed
      to address corrections are discussed.

PMID- 12518669
TI  - [Urodynamic criteria of predicting efficacy of therapy with alpha1-adrenergic
      blockaders in patients with benign prostatic hyperplasia].
AB  - AIM: As baseline urodynamic parameters do not correlate well with response to
      medical treatment for lower urinary tract symptoms (LUTS), this study was
      designed to asertain whether urodynamic parameters correlate better with response
      to alpha 1-adrenoblockers. METHODS: 23 men (mean age 64.6 +/- 9.3 years) with
      LUTS have undergone urodynamic examination prior to initiating therapy with
      terazosin titrated to 5 mg and followed for 2.5 months. Parameters of evaluation
      included IPSS symptom score, peak flow rate (Qmax), maximal detrusor pressure
      (Pmax), detrusor pressure at maximal flow (Pdet) and detrusor contraction
      duration (DCD). The correlation and predictive value of therapeutic response and
      baseline urodynamic parameters were assessed. RESULTS: For the entire group, IPSS
      decreased from 13.25 +/- 3.39 to 7.38 +/- 3.21 (44.6%), Qmax increased from 9.75
      +/- 1.95 to 11.00 +/- 3.23 ml/s (21%), Pmax decreased from 109.75 +/- 35.72 to
      93.88 +/- 20.91 cm. H2O (14.4%), Pdet decreased from 84.00 +/- 23.71 to 74.00 +/-
      15.53 cm. H2O (16.8%), DCD increased from 127.63 +/- 53.99 to 130.13 +/- 45.41s
      (2.7%). There was a weak correlation between either Pmax or Pdet and therapeutic
      response (defined as a IPSS decrease of 40% and an increase in Qmax of 30%).
      There was a significant correlation with therapeutic response of DCD > 60 s (p <
      0.05, r = 0.56). CONCLUSION: The pilot data suggest that DCD may be a useful
      urodynamic parameter to predict and optimize therapy with alpha 1-adrenoblockers.

PMID- 12518668
TI  - [Comparative evaluation of the efficacy of using terazosin and tamsulosin in
      patients with benign prostatic hyperplasia].
AB  - AIM: To evaluate effectiveness and safety of terazosin vs tamsulosin in patients
      with benign prostatic hyperplasia (BPH); to elucidate effectiveness of the use of
      tamsulosin followed by terazosin and vice versa. MATERIAL AND METHODS: Group 1 of
      BPH patients received terazosin (5 mg/day) followed in a month by tamsulosin (0.4
      mg/day). Group 2 received the same drug in the opposite sequence. The trial
      included 60 patients with symptoms of the lower urinary tracts due to BPH. The
      results were assessed on the treatment day 5-7, 14, 30 and 60 one month after the
      treatment termination. RESULTS: Terazosin and tamsulosin relieved clinical
      symptoms, reduced QOL and Qmax. One month after the treatment the symptoms
      partially returned to baseline, Qmax returned completely. In cross-over, positive
      trends were weaker. CONCLUSION: Clinical efficiency of both drugs was comparable,
      there was no cross effect. A month interval between the treatments in this case
      was insufficient. This should be taken into account when planning further
      studies.

PMID- 12518670
TI  - [Use of alpha1-adrenergic blockaders in treating voiding disorders after
      transurethral resection of the prostate].
AB  - Removal of infravesicular obstruction by transurethral resection (TUR) of the
      prostate rapidly eradicates obstructive symptoms but irritative symptoms persist.
      We studied the effect of alpha 1-adrenoblockers (A1AB) in respect of optimization
      of TUR effects. The trial was performed in 1998-2002 and included 197 patients
      treated surgically (TUR) for benign prostatic hyperplasia (BPH). 96 patients
      received no A1AB in the postoperative period (group 1). 52 patients took
      terazosine (group 2) and 49 patients were given tansulosine (group 3). IPSS
      symptoms and QoL estimation were registered monthly, the patients recorded the
      urination. After 3 and 6 months after TUR, maximal urination rate (MUR) and
      residual urine were assessed. It was found that MUR and QoL did not differ
      significantly between the groups but in groups 2 and 3 a fall in the overall
      score by IPSS was greater. The positive symptomatic improvement was achieved due
      to relief of the symptoms of urinary bladder filling corresponding to an increase
      in physiological capacity of the organ, the difference being significant (p <
      0.05).

PMID- 12518671
TI  - [Results of monotherapy with terazosin (kornam) in chronic infectious prostatitis
      patients].
AB  - AIM: To evaluate effectiveness of alpha 1-adrenoblockers (a1-AB) in patients with
      chronic non-infectious prostatitis (CP). MATERIAL AND METHODS: a1-AB
      effectiveness was studied in 28 volunteers with non-infectious CP (type IIIA).
      All the patients received terazosin (kornam, Slovenia) in a dose 5 mg/day after
      dose titration for 2-3 weeks (the initial dose was 1 mg/day). The assessment of
      the efficiency was standard with the use of frequency and severity of symptoms
      scales as well as questionnaire NIH CPSI. RESULTS: Symptomatic improvement was
      achieved in 27 patients (96%). Dysuria and intensity of pain diminished in 24
      (82%) and 26 (93%) patients. Voiding disorders proved most sensitive to a1-AB.
      Quality of life rose 2-fold. Probability of the recurrence 1 month after
      terazosin therapy was 0.29, after 6 months--0.43. Recurrent dysuria occurred in
      33%, pain--in 58%. CONCLUSION: Terazosin monotherapy in patients with non
      infectious CP results in reduction of the symptoms severity and pollakiuria
      frequency, frequency of recurrences and in improvement of quality of life. a1-AB
      in CP do not prevent recurrence in half the cases but the symptoms severity in
      recurrent disease is much weaker.

PMID- 12518673
TI  - Dentistry in the Soviet Union.

PMID- 12518672
TI  - [Use of alpha1-adrenergic blockaders in voiding disorders in women].
AB  - Alpha-adrenoblockers are commonly used to treat LUTS suggestive of benign
      prostatic hyperplasia in men. It is well known that they do not modify natural
      history of the disease but only relax the smooth muscle. Several investigations
      confirmed the presence of alpha 1-AR in the spinal cord, bladder neck, urethra
      and periurethral tissue in women (so-called female prostate). So, "prostatism
      like" symptoms seem to be not gender-specific. Therefore, alpha-adrenoblockers
      may be used in the treatment of urinary disorders in women. 32 women (mean age
      26.5 years, range 18-65) with functional BOO took a terazosin course after
      clinical and urodynamic examinations. The patients were divided into three
      groups: detrusor sphincter dyssinergia, primary bladder outlet obstruction and
      learned voiding dysfunction (dysfunctional voiding). Patients with urethral
      stricture, pelvic organ prolapse, bacteriuria were excluded. The initial dose was
      1 mg/day, then it was increased to 5 mg/day. The treatment course lasted 2
      months. Patients recorded the time and volume of every void three days before
      treatment and last three days of drug therapy. All the patients were satisfied
      with the results of the treatment. We noticed an increase in the maximal flow
      rate (55.4%), a decrease of delay time (48.9%) and nocturia (52.9%). CONCLUSIONS:
      Specific agents, such as alpha-adrenoblockers, in low dosage may be effective in
      women with urinary tract disorders in case of careful and comprehensive
      evaluation of functional BOO.

PMID- 12518674
TI  - What it means to volunteer.

PMID- 12518675
TI  - Volunteerism in action: James and Louise Addison Kiwanis Dental Center.

PMID- 12518676
TI  - Called to serve.

PMID- 12518677
TI  - Answering a call to service in Abilene.

PMID- 12518678
TI  - Community Dental Clinic, Amarillo.

PMID- 12518679
TI  - Dentistry overseas--teaching dental public health at the Faculty of Odonto
      Stomatology, Ho Chi Minh City, Vietnam.

PMID- 12518680
TI  - Times donated--Faculty of Odonto-Stomatology (FOS) Medical University, Ho Chi
      Minh City.

PMID- 12518681
TI  - A mission to remember.

PMID- 12518682
TI  - One light in the darkness.

PMID- 12518683
TI  - A journey back in time.

PMID- 12518684
TI  - Call to service: Belize Mission Project from beginning to present.

PMID- 12518685
TI  - Providing volunteer dentistry in a foreign country.
AB  - I would highly recommend taking a dental mission trip if the opportunity presents
      itself. While the work is demanding, there are few situations that produce such a
      high level of personal satisfaction. There are several organizations that sponsor
      medical/dental trips to foreign countries such as Faith In Practice and the
      Christian Medical and Dental Society. You can also check with your local place of
      worship. Many opportunities can be found by simply making your desire to serve
      known. You also can provide care without leaving the State of Texas. The second
      annual Texas Mission of Mercy will be held in Tyler, Texas. The first event was a
      huge success, and this year's event promises to be even more successful!

PMID- 12518686
TI  - Oral and maxillofacial pathology case of the month. Candidiasis.

PMID- 12518687
TI  - Practical solutions for increasing patients' acceptance of your financial
      options.

PMID- 12518688
TI  - Consider the evidence.

PMID- 12518689
TI  - Warning regarding printed digital images.

PMID- 12518690
TI  - A study of orofacial bacterial infections in elderly Nigerians.
AB  - This retrospective study was designed to determine the pattern of occurrence, and
      principles of management of orofacial bacterial infections in elderly Nigerians.
      Ninety-two patients aged 55-90 years (mean +/- SD 62.4 +/- 7.5 years), were
      admitted into the study (male:female ratio 1.1:1). The origin of orofacial
      infection was predominantly odontogenic and the lower face was three times more
      commonly involved. The percentage of patients with underlying systemic disease
      was 16.2%. Patients with underlying disease had a 3.5 times greater risk of
      developing orofacial infections. Similarly, a significant correlation was
      demonstrated between both sexes of patients with orofacial infections and
      underlying illness (P < 0.05). There was a general delay before presenting for
      treatment (average 19.5 weeks) and the mortality rate was 3.3%. The study
      findings demonstrate that a significant relationship exists between elderly
      Nigerians with orofacial infections and systemic disease.

PMID- 12518691
TI  - An implant-supported auricular prosthesis: a team effort between two South
      African tertiary institutions.

PMID- 12518692
TI  - The removal of impacted third molars. Position paper of the South African Society
      of Maxillofacial and Oral Surgeons.

PMID- 12518693
TI  - Prophylactic antibiotic use in oral surgery--a review of current concepts.

PMID- 12518694
TI  - A review of the neurovascular supply of the mandible.

PMID- 12518695
TI  - General practitioner's radiology case 6. Periostitis ossificans.

PMID- 12518696
TI  - Determining factors for implant referral rates.
AB  - The research findings indicate that the field of implant dentistry will only grow
      at a moderately low level unless certain changes are made. Findings indicated
      that the effort by the implant companies has been nothing short of dramatic, and
      yet almost 60% of restorative doctors do not participate annually in any implant
      case. There was no clear indication that younger restorative doctors will
      significantly increase the number of implant referrals, as their overall implant
      education has not dramatically differed from those dentists who graduated in
      earlier years. Once the research was completed, it became obvious to Levin Group
      that the driving force behind implant referral growth will be implant surgeons,
      because of their one-to-one relationship with restorative doctors. The Levin
      Group Implant Management and Marketing Consulting Program is based on approaching
      restorative doctors in several different levels, starting with awareness all the
      way through to case facilitation and long-term tracking and communication.
      Finally, a continuing marketing/education effort needs to be consistently in
      place with effective materials, not only to create a high level of awareness, but
      also to motivate restorative doctors to refer cases and then work through the
      case with the implant surgeon to a satisfactory completion for the restorative
      doctor, implant surgeon, and patient. While the surgical insertion of implants
      may seem to carry a high-profit margin relative to the restoration of implants,
      the truth is that the restoration of implants usually provides a 40% higher
      profit margin for the restorative doctor than traditional dental services. One of
      the key issues is that referring doctors have not necessarily learned how to set
      fees and present cases with regard to implant dentistry. The key factor here is
      to ensure that the patient understands that implant services involve higher fees
      than traditional services, because of the necessarily higher levels of
      experience, education, and cost associated with implant dentistry. It is also
      important to emphasize to patients that the quality of life far outweighs the
      differential in fees.

PMID- 12518697
TI  - Immediate loading.

PMID- 12518698
TI  - Delayed onset of altered sensation following dental implant placement and mental
      block local anesthesia: a case report.
AB  - A case of a delayed-onset post-operative altered sensation of the mental nerve is
      reported with speculations as to etiology. There is a discussion concerning
      intraoperative radiographs and osteotomy positioning. When postoperative altered
      sensation occurs, etiologic considerations should always include local anesthetic
      administration technique. The importance of pulp testing from the first molar to
      the contralateral lateral incisor is key to determining whether the deficit is in
      the mandibular nerve or only the mental nerve, which may be a result of mental
      block local anesthetic administration and not implant placement. This
      differentiation may be important in treatment and/or legal exposure. The altered
      sensation was probably caused by the mental block anesthetic technique. The
      partial anesthetic area in this case was probably a result of crossover
      innervation from the contralateral mental nerve.

PMID- 12518699
TI  - Diagnoses, clinical classification, and proposed treatment of spontaneous early
      exposure of submerged implants.
AB  - Spontaneous early exposure of implants can become a serious complication during
      the initial healing phase. These early perforations and partial exposure of the
      coverscrews are a foci for plaque accumulation which, if left untreated, may
      result in inflammation, damage to the periimplant mucosa, and possible bone loss.
      Sometimes, these exposures are so small so as not to be clinically visible. This
      article presents methods of diagnoses of perforated mucosa around submerged
      implants. In addition, an easy-to-use classification of the spontaneous early
      exposure is proposed. Treatment modalities to prevent or intercept mucositis
      during the initial healing phase, when early exposures occur, are suggested.

PMID- 12518700
TI  - Management of severe hypodontia.
AB  - Developmental absence of one or more teeth referred to as hypodontia is
      frequently encountered in dental practice, whereas severe hypodontia is a rare
      developmental dental anomaly. A case of severe hypodontia is presented. It was
      successfully treated with osseointegrated implants.

PMID- 12518701
TI  - Immediate implant in extraction socket with acellular dermal matrix graft and
      bioactive glass: a case report.
AB  - A buccal plate destroyed as a result of a longitudinal root fracture was
      completely restored by the use of a Frialit-2 implant placed in the alveolus of
      the fractured maxillary left first bicuspid. An acellular dermal matrix material
      was used as a membrane barrier to cover the implant, and a bioactive glass was
      used as grafting material. After 6 months, the defect around the implant was
      completely filled by mineralized tissue.

PMID- 12518702
TI  - Assessment of endodontically treated teeth adjacent to proposed implant sites.
AB  - Many partially dentate dentitions are now being restored using dental implants;
      but assessment of endodontically treated teeth adjacent to the proposed implant
      sites has seldom been reported. Assessment criteria are given for sound- and
      endodontically compromised teeth to ensure adequate preimplant preventive and
      restorative treatment and to minimize the chances of failure of dental implants
      adjacent to these teeth. Cases are used to illustrate pitfalls in the treatment
      planning process.

PMID- 12518703
TI  - Periimplant probing: positives and negatives.
AB  - Periodontium in normal dentition is not as it is surrounding an implant area.
      Thus, periodontal probing with normal dentition is not similar to periimplant
      probing. The periimplant probing protocol should be different from periodontal
      probing because of inherent anatomical differences. The aim of this paper is to
      review the topics related to periimplant probing and to draw inferences to
      develop a periimplant probing protocol.

PMID- 12518704
TI  - Management of deficient anterior maxillary alveolus with mandibular
      parasymphyseal bone graft for implants.
AB  - This paper discusses the use of autogenous bone graft from the symphyseal region
      of the mandible to widen the deficient anterior maxilla. Compressing short or
      narrow implants into deficient ridges is a poor technique that often fails to
      correctly replace ridge anatomy or afford stable restorations. Patients who were
      missing a maxillary incisor, and exhibiting a loss of supporting bone in the
      area, were found suitable for this technique. Ten patients were included in the
      study. In the anterior maxilla, the thin cortices can be split, and a
      corticocancellous bone graft from the mandibular symphyseal region can be
      positioned on the labial-buccal cortex. This surgical procedure enables implant
      placement in previously deficient bone within the maxilla. In comparison with
      other techniques, the use of a mandibular symphysis graft technique offers ease
      of access, good bone quantity for localized repair, a corticocancellous block
      graft morphology, low morbidity, decreased complaints of postoperative sensory
      disturbances and discomfort, and minimal graft resorption. An improved bone
      density results along with a shorter healing time as compared with other methods
      for bone repair. A success rate of 81.2% was obtained after a mean follow-up
      period of 3 years.

PMID- 12518705
TI  - Microvessel density in alveolar ridge regeneration with autologous and
      alloplastic bone.
AB  - PURPOSE: The purpose of this study was to conduct a comparative
      immunohistochemical evaluation of microvessel density (MVD) in alveolar sites
      augmented with autologous bone or Bio-Oss. MATERIALS AND METHODS: Eighteen
      patients participated in this study. All patients presented maxillary ridge
      defects. These defects were filled in a random fashion with autologous bone or
      Bio-Oss. Endosseous implants were inserted after a mean of 3 months in the sites
      augmented with autologous bone and after a mean of 6 months in the sites
      augmented with Bio-Oss. As part of the implant site preparation, a trephine was
      used to harvest bone cores. As control, bone cores retrieved in nonaugmented
      sites were used. The mean value of MVD in control bone was 25.6 +/- 3.425. In the
      sites augmented with autologous bone, the MVD was 29.8 +/- 4.4, while in the
      sites regenerated with Bio-Oss, the MVD was 29.7 +/- 2.4. The statistical
      analysis showed that the difference in MVD between control bone and autologous
      bone (P = 0.057) and between control bone and Bio-Oss (P = 0.023) was
      statistically significant. The difference between the sites regenerated with
      autologous bone and those regenerated with Bio-Oss was not significant (P =
      0.6889). CONCLUSIONS: Our results show that both sites augmented with autologous
      bone and Bio-Oss presented a higher and statistically significant quantity of
      microvessels compared with control specimens. No significant differences were
      found when comparing the MVD of the sites regenerated with autologous bone and
      those regenerated with Bio-Oss. The retrieval time was, however, a mean of 3
      months for the autologous bone sites and a mean of 6 months for the Bio-Oss
      sites. These data could support the hypothesis of faster healing for the sites
      augmented with autologous bone.

PMID- 12518706
TI  - Short-term bone responses to hydroxyapatite cement.
AB  - PURPOSE: The purpose of this study was to evaluate the short-term wound healing
      and repair at the tissue/cement interface with different hydroxyapatite cement
      formulations. MATERIALS AND METHODS: Three groups of Sprague-Dawley rats were
      implanted with HAC for 3, 7, or 14 days. The medial femur-tibia sites on each leg
      of the animals were used to create four separate 1.5-mm defects, which were
      filled with HAC (Bone-Source, Howmedica-Leibinger, Inc.) mixed with either water
      (W) as a control, an accelerant (0.1 M sodium phosphate, SP), or a stabilizer (1%
      hydroxypropylmethyl cellulose, HPMC) as diluents. At the appropriate
      postimplantation times, the animals were euthanized and tissue-implant blocks
      were prepared for qualitative histopathologic evaluations. RESULTS:
      Osseoconduction around and into the HAC was observed with all three cement
      formulations and the control (unfilled) site by day 7 and continued through day
      14. The histologic staining did not reveal resorption lacunae or other cellular
      activities characteristic of osteoclast degradation of HAC. These results
      suggests that other processes, perhaps physical-chemical in nature, contributed
      to the initial degradation of the HAC following surgical placement. Structural
      stability of HAC was noted when using HPMC as the diluent. However, when either W
      or SP were employed, dissociation (washout) of the HAC into the surrounding
      tissue was noted. CONCLUSION: HAC is prone to in situ physical-chemical breakdown
      before the completion of the setting reaction. Diluents designed to stabilize or
      accelerate the HAC mixture appeared to improve the handling properties of the HAC
      without compromising the biological characteristics of the cement.

PMID- 12518707
TI  - Multiple-pool cell lifespan model of hematologic effects of anticancer agents.
AB  - The leukopenic effects of anticancer agents are described using a semi
      physiologic multiple-pool cell lifespan model. The time course of
      myelosuppression in relation to the drug concentration vs. time profile was
      characterized using a three pool indirect model. The proliferation and maturation
      stages of myeloid cells in the bone marrow and cell removal from the circulation
      were quantitated with a cell life-span concept. Drug effects were assumed to take
      place in the bone marrow based on irreversible linear or capacity-limited
      cytotoxicity. Mathematical derivations and computer simulations (Adapt II) were
      used to examine the properties of the model. Data from the literature were also
      analyzed. Cell response profiles after therapy typically exhibit a lag period,
      reduction to a nadir, and return to baseline. The predicted values of the time
      periods of granulopoiesis were 10-14 days for proliferation, and 1-6 days for
      maturation of progenitor cells in the bone marrow. The proposed irreversible
      mechanism of cell killing by anticancer drugs explains previously observed
      relationships between leukocyte nadir counts and exposure to the drug and/or
      duration of drug concentrations above some threshold level. The model was applied
      to literature data for paclitaxel and etoposide effects on leukocyte counts. The
      predicted value of KC50 for paclitaxel ranged from 0.004 to 0.2 microgram/mL and
      for etoposide 2 micrograms/mL. The present model accounts for drug-induced
      leukopenia using a physiologic cell production and loss model and irreversible
      cytotoxicity in a precursor pool.

PMID- 12518708
TI  - Clinical trial simulation using therapeutic effect modeling: application to
      ivabradine efficacy in patients with angina pectoris.
AB  - Ivabradine is a new bradycardic agent with a potential indication for stable
      angina pectoris. To investigate the best compromise between efficacy, safety,
      drug regimen, and number of patients to include in a phase III study, we
      conducted Monte Carlo simulations using a full therapeutic model. The binary
      clinical outcome, chest pain, was simulated using a physiologic model in which
      the coronary reserve was derived from the heart rate. Safety was defined as being
      heart rate dependent. Using real data to build a pharmacokinetic-pharmacodynamic
      model controlling drug effect (i.e., heart rate decrease), and resampling heart
      rate profiles from the database, 100 clinical trials (N = 200) were simulated for
      five oral doses (2.5, 5, 10, 20, and 40 mg QD or BID) of ivabradine. Only 25% of
      the simulated trials showed a significant effect of ivabradine with doses up to
      10 mg QD, and 48 and 55% of the trials with doses of 10 mg BID and 20 mg QD,
      respectively, and more than 80% of the trials with a 40 mg daily dose. For
      safety, 4% of patients had at least one adverse event in the untreated group, and
      from 5 to 13% in the treated groups for the lowest to the highest dose,
      respectively. The number of subjects to include in a future trial to obtain a 15%
      decrease in chest pain under the assumption of a 68% base risk, is 239 subjects
      per group with 10 mg BID or 196 with 20 mg QD. These results illustrate how
      clinical trial simulations including a PK/PD model as well as a physiopathologic
      mechanistic model, describing the relationship between the intermediate and
      clinical endpoint, and the resampling of real patients from a large database can
      help in designing future phase III trials.

PMID- 12518709
TI  - Gastric acid secretion in the dog: a mechanism-based pharmacodynamic model for
      histamine stimulation and irreversible inhibition by omeprazole.
AB  - A mechanism-based pharmacodynamic model was used to describe the inhibitory
      effect by omeprazole on gastric acid secretion measured after histamine
      stimulation in the dog. The model identifies parameters that are related to the
      physiological system, the histamine stimulation, and the irreversible effect of
      omeprazole on the H+, K(+)-ATPase enzyme. Four different experiments with
      omeprazole (Exps. 1-4) and two placebo experiments were performed in each of the
      four Heidenhain pouch dogs used. For placebo and experiments 1-3, saline or
      omeprazole 0.81 mumol/kg was infused during 3 hr with measurements of histamine
      stimulated gastric acid secretion in two periods of 3.5-6.5 hr, one period
      starting just before the omeprazole infusion and a second later period up to 29
      hr post infusion. In experiment 4, 0.18 mumol/kg of omeprazole was infused for
      22.5 min and gastric juice was collected for 5 hr post infusion. The response
      data was well described by the model. Similar parameter estimates were obtained
      by three different analysis methods; naive pooling, two-stage method and
      nonlinear mixed effects modeling. The elimination rate constant for the H+, K(+)
      ATPase enzyme, kout, was estimated to be 0.040 hr-1, corresponding to a half-life
      of about 17 hr. This rate constant determines the duration of omeprazole
      inhibition after long-term exposure. For short-term omeprazole exposure the
      duration is determined by the rate constant for transfer of enzymes from active
      to resting state, estimated to be 1.88 hr-1. The second-order rate constant for
      histamine stimulation was estimated to be 0.064 hr-1 per histamine concentration
      unit and the maximum acid secretion was estimated to be 5.0 mmol H+/30 min. The
      second-order rate constant for the irreversible binding of omeprazole to H+, K(+)
      ATPase, kome, was estimated to be 2.39 L/mumol.hr. By modeling the histamine
      induced baseline response simultaneously with active treatment, predictions of
      the response are possible not only following different dosing regimens of
      omeprazole, but also following different degrees of histamine stimulation.

PMID- 12518710
TI  - Modeling nicotine arterial-venous differences to predict arterial concentrations
      and input based on venous measurements: application to smokeless tobacco and
      nicotine gum.
AB  - Significant arterio-venous differences in nicotine concentrations have been
      observed during and after cigarette smoking, nicotine nasal spray, and
      intravenous nicotine administration. In this paper we describe a novel
      mathematical method for estimating arterial blood levels from venous blood level
      data. The model allows to quantify: (i) the influence of the microcirculation in
      the hands and forearm on the distribution of nicotine, and (ii) the influence of
      disregarding the venous to arterial circulation in the estimate of systemic
      inputs. We also (iii) propose a general method to predict arterial concentrations
      and inputs given venous data. The basic model we adopt is based on the
      relationship Cv = T * Ca, where Cv and Ca are the concentration in the venous and
      arterial site, respectively, T is the arterio-venous transfer function and *
      indicates convolution. We use empirical data to estimate T. We then compare
      estimates of systemic inputs to the venous site obtained taking into account the
      transfer function or, as usually done, disregarding it. The relationship we use
      to compare estimated inputs are: Cv = T * ka * A (where Ka is the arterial
      disposition function and A the systemic input), and Cv = Kv * A (where Kv is the
      venous disposition function), respectively. Finally, the estimated transfer
      function allows to estimate (average) Ca or A given arbitrary venous data. (i)
      Our analysis suggests that a bi-exponential T is needed to describe observed
      arterial-venous differences. The estimated transfer function indicates that no
      elimination of nicotine is involved in the forearm. (ii) Disregarding T, as
      usually done, erroneously obtains too complex venous input functions (because
      these input functions incorporate T). (iii) Disregarding T erroneously estimates
      significantly higher total inputs. (iv) Using the proposed model and previously
      published venous nicotine level data we predict substantial arterial-venous
      differences in blood nicotine levels for smokeless tobacco and nicotine gum. The
      use of disposition functions obtained from venous data may lead to erroneous
      estimation of the rates of entry into the circulation and systemic
      bioavailability for many drugs.

PMID- 12518711
TI  - Commentary on significance levels for covariate effects in NONMEM.

PMID- 12518712
TI  - President's report.

PMID- 12518713
TI  - New trails blazed in the Upper Peninsula.

PMID- 12518714
TI  - Software. MNA members develop computer application to track nursing outcomes.

PMID- 12518715
TI  - Retirement. Will you be comfortable?

PMID- 12518716
TI  - Identifying and modifying barriers to HIV testing and prevention.

PMID- 12518717
TI  - First human trial of "global" HIV vaccine launched.

PMID- 12518718
TI  - Recent research in HIV infection, part 2.

PMID- 12518719
TI  - Strategies to improve access to sterile syringes for injection drug users.
AB  - The high prevalence of infection with HIV and other blood-borne pathogens in
      injection drug users (IDUs) is directly related to the lack of syringe access.
      Needle exchange programs (NEPs), syringe prescription, and syringe deregulation
      are 3 approaches to increasing access to sterile syringes for IDUs. The benefits
      of NEPs have been repeatedly demonstrated, but the impact of NEPs has been
      limited by a lack of federal funding. Syringe prescription for IDUs is a
      promising new strategy supported by many organizations; legalizing syringe
      purchase and possession has led to a substantial improvement in syringe access in
      many states. Because each approach has unique advantages, providing IDUs with a
      variety of options for syringe access is likely to be most beneficial.

PMID- 12518720
TI  - Editorial comment: syringe access versus syringe disposal--the law of diminishing
      returns?

PMID- 12518721
TI  - ADA's Nutrition Trends Survey: a tool for all dietetics professionals. American
      Dietetic Association.

PMID- 12518722
TI  - ProC Global assay in the evaluation of women with history of severe preeclampsia
      or HELLP syndrome.
AB  - Preeclampsia/HELLP syndrome has been associated with a high incidence of defects
      in the protein C pathway and increased anticardiolipin-antibodies/lupus
      anticoagulants. It is also apparent that thrombophilia is responsible for other
      pregnancy complications, such as recurrent spontaneous abortion, fetal growth
      restriction, intrauterine fetal death, and abruptio placentae. ProC Global is a
      new global dotting assay designed to evaluate the abnormalities in the protein C
      anticoagulant pathway. It is based on the ability of endogenous activated protein
      C, generated by activation of protein C by Protac, to prolong an activated
      partial thromboplastin time. A total of 61 patients with a history of severe
      preeclampsia or HELLP syndrome and 61 normal pregnant women (controls) were
      evaluated, 15 of whom had factor V Leiden mutation, 12 had protein C/S
      deficiency, 30 had a repeated lupus anticoagulants, and 27 increased
      anticardiolipin antibodies (ACA). All carriers of factor V Leiden mutation (N=15)
      as well as all the patients with low activated protein C (APC) resistance ratio
      (N=15) had a ProC Global normalized ratio (NR) less than 0.80 (sensitivity 100%).
      Twenty-four patients positive for the lupus anticoagulants (LA) and 19 patients
      positive for ACA (>5.0 IgG U/mL) had a ProC Global NR less than 0.8, while six
      and eight, respectively, had a ProC Global NR greater than 0.8 (sensitivity, 70%
      80%). The detection of a reduced protein C/protein S activity (<70%) was low
      (sensitivity, 33%-44%). In 25 cases with pathologic ProC Global results, a
      thrombophilic defect (protein S/LA/ACA without APC resistance) was diagnosed in
      18 women; but in 7 cases, no known thrombophilic defect was present. ProC Global
      is a new screening test to identify patients with defects of the protein C system
      and an activated dotting system in preeclampsia but cannot correctly cover each
      thrombophilic component.

PMID- 12518723
TI  - Obstetric brachial plexus palsy: a clinical and electrophysiologic evaluation.
AB  - BACKGROUND: Obstetrical brachial plexus palsy (OBPP) occurs as sequelae of birth
      related trauma, antenatal and parturition related complications. It is associated
      with varying degrees of functional disability. Electrodiagnostic studies (EDS)
      are an adjunctive tool and help to localise and prognosticate the outcome of
      OBPP. METHODS: Fourteen children, presenting with OBPP to the Clinical
      Neurophysiology Lab, were analyzed. Details of birth history were obtained, and
      EDS were performed to characterize the lesion. RESULTS: The age ranged from one
      month to one year. Ten had unilateral and four bilateral brachial palsy. On EDS,
      five had pan-plexus, six predominantly upper plexus and three lower plexus
      involvement. A poor re-innervation pattern on EMG correlated with inadequate
      recovery. CONCLUSION: OBPP, a condition associated with considerable disability,
      needs to be prevented. Electrodiagnostic studies are a useful adjunctive tool for
      characterizing the site of injury and prognostication.

PMID- 12518724
TI  - [Photodynamic therapy for age related macular degeneration with and without
      antioxidants].
AB  - BACKGROUND: Antioxidants may affect the lipid components of membrane receptors.
      The purpose of this study was to determine whether treatment with antioxidants
      after photodynamic therapy for age-related macular degeneration (AMD) improves
      visual acuity recovery time after a flicker test METHODS: The study was conducted
      in a university-affiliated ophthalmology clinic in Bologna, Italy, from April
      2000 to April 2001. Thirty-five patients (21 men and 14 women aged 55 to 86 years
      [mean 72 (standard deviation [SD] 8.4) years]) with bilateral AMD and neovascular
      membranes were enrolled in the study. Patients were randomly assigned to either
      receive (20 patients) or not receive (15 patients) vitamin E (200 mg/d given
      orally) and polyunsaturated fatty acids (1,000 mg/d given orally) after
      photodynamic therapy. The outcome measures were visual acuity (logMAR) after 20,
      40 and 60 days, and retinal metabolic function, as evidenced by visual acuity
      recovery after the Magder flicker test. RESULTS: There was no significant
      difference in visual acuity between the two groups at 20, 40 or 60 days. At 20
      days, the visual acuity recovery time was significantly shorter in the group that
      received antioxidants than in the group that received photodynamic therapy only
      (phase II .94 [SD 0.39] minutes vs. 2.56 [SD 0.57] minutes, phase II 2.13 [SD
      0.68] minutes vs. 2.83 [SD 0.60] minutes, and phase III 2.19 [SD 0.70] minutes
      vs. 2.92 [SD 0.65] minutes) (p < 0.001). There was no significant difference
      between the two groups at 40 or 60 days. INTERPRETATION: Treatment with
      antioxidants after photodynamic therapy for AMD improves retinal metabolic
      function in the short term but not in the medium term.

PMID- 12518725
TI  - Descending necrotizing mediastinitis.
AB  - Descending necrotizing mediastinitis (DNM) is an infrequent clinical entity. DNM
      is the result of infection originating in the oropharyngeal regions and spreading
      along cervical fascial planes to cause mediastinal abscess and sepsis. Even with
      prompt recognition and treatment, the mortality and morbidity associated with DNM
      are appreciable. The opportunities for successful outcome are improved with
      liberal use of computed tomography, aggressive surgical therapy, and a
      multidisciplinary team approach. We report a case of DNM that illustrates how
      these principles were employed in the successful management of this rare and
      often fatal condition.

PMID- 12518726
TI  - How to get all the 99214s you deserve.

PMID- 12518731
TI  - What is postmastectomy pain syndrome?

PMID- 12518732
TI  - Protecting a hemodialysis fistula.

PMID- 12518735
TI  - Who should receive the influenza vaccine?

PMID- 12518745
TI  - How to streamline your risk assessment form.

PMID- 12518749
TI  - Pasteurella multocida.

PMID- 12518750
TI  - You routinely administer combination drugs...but do you know what's in them?

PMID- 12518751
TI  - Understanding pneumothorax.

PMID- 12518752
TI  - Myths and facts...about polycystic ovarian syndrome.

PMID- 12518753
TI  - 9 tips for success.

PMID- 12518763
TI  - Evaluation of recombinant cytochromes P450 activity in metabolic pathways.

PMID- 12518764
TI  - Delayed discharge and hospital congestion....And another is primary care
      occurring in hospitals.

PMID- 12518765
TI  - Managing acute appendicitis. Neuroimmune appendicitis may be distinct
      pathological entity.

PMID- 12518766
TI  - Preventing and treating eclamptic seizures. Other causes of death need to be
      treated.

PMID- 12518767
TI  - Alcohol handrubs v soap. Alcohol handrub removes methicillin resistant
      Staphylococcus aureus.

PMID- 12518768
TI  - Noninvasive ventilation allows gastrostomy tube placement in patients with
      advanced ALS.

PMID- 12518769
TI  - Alosetron for irritable bowel syndrome. Risks of using alosetron are still
      unknown.

PMID- 12518770
TI  - [Early irradiation with radiochemotherapy for limited-stage small cell lung
      cancer is superior to late irradiation].

PMID- 12518771
TI  - Tamoxifen and raloxifene may benefit women at high risk for breast cancer.

PMID- 12518772
TI  - Specific comments on echocardiogram reports increase compliance with endocarditis
      guidelines.

PMID- 12518773
TI  - New guidelines suggest childhood training for cardiovascular health.

PMID- 12518774
TI  - Case marks evolution in antibiotic drug resistance.

PMID- 12518775
TI  - Receptor-dependent and genomic-independent actions of estrogen in vascular
      protection.
AB  - Functional evidence for a rapid, receptor-dependent and genomic-independent
      action of estrogen in vascular cells continues to accumulate. Although the nature
      of the receptor is not yet clear, some of the hormone-induced effects can be
      blocked by known estrogen antagonists (e.g., ICI 182,780) and can be mimicked by
      membrane-impermeable forms of estrogen. Because the endothelial output of nitric
      oxide (NO) is a major regulator of several cardiovascular functions, regulation
      of NO production has received a lot of attention as a potential mechanism for the
      cardiovascular protection offered by estrogen. There is ample evidence that
      estrogen can stimulate NO production and activate endothelial NO synthase (eNOS)
      both in vitro and in vivo. Recent investigations have shown that estrogen's rapid
      stimulatory action on eNOS is mediated by the activation of phosphatidylinositol
      3-kinase (PI3-K) and protein kinase B (PKB)/Akt pathway among other signaling
      systems. Although these effects are estrogen receptor-dependent, they are rapid
      (on the order of a few minutes) and transcription-independent and thus represent
      genomic-independent but receptor-mediated effects of a steroid operating in
      vascular cells. In this review, recent evidence for such mechanisms is
      summarized, and the role of estrogen receptors in vivo is also briefly discussed.

PMID- 12518776
TI  - Bronchial responsiveness and lung function related to cigarette smoking and
      smoking cessation.
AB  - BACKGROUND: The relationships between bronchial responsiveness and both cigarette
      smoking and smoking cessation are still controversial. METHODS: To investigate
      the effects of cigarette smoking and smoking cessation on bronchial reactivity
      and the level of pulmonary function, bronchial responsiveness to methacholine
      using the forced oscillation method, the transfer factor, and spirometry were
      measured in 180 nonsmokers, 109 current smokers, and 82 ex-smokers. The following
      indices of bronchial responsiveness were used: (1) baseline respiratory
      resistance (Rrs); (2) the cumulative dose of methacholine (DA) causing an
      increase in Rrs by twice the baseline values (bronchial sensitivity); and (3) the
      slope of linearly decreased respiratory conductance (SGrs) representing bronchial
      reactivity. RESULTS: Current smokers had significantly higher baseline Rrs
      (p<0.001) and bronchial responsiveness than did nonsmokers and ex-smokers. In
      24.7% of smokers, Rrs increased by twice or more upon challenge with methacholine
      (responders), compared with 0% of nonsmokers (p<0.0001) and 19.5% of ex-smokers
      (p=0.28). SGrs for responders among ex-smokers was found not to differ from that
      for responders among smokers. However, smokers had a significantly lower DA of
      inhaled methacholine than did ex-smokers. Cigarette smoking was also associated
      with an appreciable reduction in FEV1/FVC (forced expiratory volume in 1s/forced
      vital capacity), DLCO (carbon monoxide diffusing capacity), and DLCO/VA (alveolar
      volume). CONCLUSION: There seems to be a partially reversible phenomenon that
      leads to improvement in airway responsiveness and DLCO upon smoking cessation.

PMID- 12518777
TI  - Reconstructing humerus defects after tumor resection using an intramedullary
      cortical allograft strut.
AB  - BACKGROUND: The humerus is a frequent involvement site of benign bone lesions.
      Various reconstruction methods have been adopted to restore the defect after
      excavating the lesion and/or to treat associated pathological fractures. In this
      study, we reviewed the clinical outcomes of using allogenous cortical struts to
      the treatment of patients with large humeral defects resulting from benign bone
      lesions, and investigated the mid-term fate of implanted allografts. METHODS:
      From 1988 through 1997, 29 patients with space-occupying humeral lesions were
      treated by eradication of the tumor and reconstruction with an intramedullary
      allogenous cortical strut. No additional internal fixation was needed for
      support. Clinical data were recorded, and functional and radiographic results
      were evaluated. RESULTS: The sizes of defects after eradication of the lesions
      ranged from 61 to 122 ml (mean, 92 ml). The patients were followed for a mean of
      8.8 years. One local recurrence was noted and was successfully treated by
      repeating the procedure. All patients achieved good to excellent functional
      results. Follow-up radiographs showed complete healing of the defects, with
      partial to complete incorporation of the allografts into the host bones. Children
      had a better chance of complete allograft incorporation than adults. CONCLUSION:
      Intramedullary allogenous cortical struts act as internal splint mechanically and
      bone graft material biologically. The combined use of intramedullary allogenous
      cortical struts and chipped cancellous bone grafts provided good stability and
      healing probability for large osseous defects in the humerus without the need for
      implant fixation. Allograft incorporation occurred slowly in adults and might not
      achieve complete incorporation in adults.

PMID- 12518778
TI  - Clinical evaluation of a new model of self-obtained method for the assessment of
      genital human papilloma virus infection in an underserved population.
AB  - BACKGROUND: We designed a self-sampling method to collect exfoliated genital
      cells for human papilloma virus (HPV) detection. The aim was to assess whether it
      was suitable as an assistant tool for the early detection of cervical pre-cancer
      and cancer in a special category of the women who are not frequently screened for
      cervical cancer. METHODS: We compared the results of HPV detection that were self
      obtained and physician-obtained cervical swabs from the same patient that were
      analyzed using hybrid capture II assay. The diagnostic rate of cervical pre
      cancer and cancer between self-obtained method and physician-obtained method were
      analyzed. RESULTS: A total of 1194 women were prospectively registered from
      September 1997 through September 1999. Among them, 144 (12.1%) of self-test
      samples and 155 (13%) of physician-obtained samples were oncogenetic associated
      HPV positive. Statistically, no significant differences existed in the screening
      rate for cervical cancer using either the self-collected samples or the physician
      obtained samples (p > .05). The sensitivity of cervical precancer or cancer
      detection using self-obtained HPV testing was higher (96.3%) as compared with the
      Pap smear (79.2%) (p < .02). CONCLUSION: The detection correlation of the HPV
      test between the self-obtained method and physician-obtained method was 93%. Our
      results indicated that self-sampling was a reliable method for testing for HPV.
      The identification of HPV infection through the self-obtained method can be used
      in early identification of high-risk women with cervical precancer and cancer
      especially in underserved populations.

PMID- 12518779
TI  - Retinal capillary hemangiomas: clinical manifestations and visual prognosis.
AB  - BACKGROUND: To describe the clinical features, visual outcomes, and therapeutic
      complications of patients with retinal capillary hemangiomas. METHODS: A
      retrospective, non-comparative, observational case study of patients diagnosed
      with retinal capillary hemangiomas was conducted. Twelve patients (13 eyes) at
      Chang Gung Memorial Hospital of Kaohsiung from July 1987 to June 2001 were
      reviewed. Pre- and post-treatment visual acuity and ocular complications are
      described. RESULTS: One patient had bilateral and another had unilateral
      juxtapapillary hemangiomas. All of the other 10 patients were diagnosed with
      peripheral retinal capillary hemangiomas. More patients had retinal capillary
      hemangiomas located in the temporal peripheral retina and all had endophytic
      growth patterns. No patient met the diagnostic criteria of von Hippel-Lindau
      disease. Visual acuity levels of peripheral retinal hemangiomas without exudative
      retinal detachment often remained the same after focal laser treatment. Two
      patients received vitreoretinal surgery. Patients with juxtapapillary hemangiomas
      had variable visual outcomes and visual field defects during follow-up.
      CONCLUSION: Early diagnosis of capillary hemangiomas in the retinal periphery and
      treatment by focal laser produced good visual outcomes. If untreated, the tumors
      may eventually be complicated with exudative retinal detachment and have a worse
      visual prognosis even with vitreoretinal surgery.

PMID- 12518780
TI  - Secondary syphilis-related oral ulcers: report of four cases.
AB  - Establishing a diagnosis of syphilis, whatever the stage of the disease, can be
      difficult because syphilis is a great mimic in clinical morphology and histology.
      Many patients infected with venereal diseases have oral manifestations, but very
      few dentists and physicians have the proper experience to diagnose syphilis or
      other STDs from oral lesions. Oral secondary syphilis appears to be very
      uncommon, and few cases have been reported over the recent past. We present 4
      patients who developed secondary syphilis-related oral lesions of moist ulcers,
      irregular linear erosions termed 'snail-track' ulcers, or erythematous mucous
      patches on the labial mucosa, buccal mucosa, palate, or tongue. Concurrent human
      immunodeficiency virus (HIV) infection was diagnosed in 1 patient. The
      histological examination in 2 patients showed dense subepithelial inflammatory
      cell infiltration comprised predominantly of plasma cells, and it was of
      practical help in the diagnosis of syphilis. The diagnostic value of a
      histological examination, serologic tests, and treatment of syphilis are
      discussed. Obviously, coinfection with HIV will complicate the clinical
      presentation, diagnosis, and management of syphilis. Concurrent HIV infection
      should be considered in any patient with a sexually transmitted disease including
      syphilis.

PMID- 12518781
TI  - Endoscopic sinus surgery for solitary abducens palsy in patients with isolated
      sphenoid sinus disease: report of four cases.
AB  - Solitary abducens palsy secondary to isolated sphenoid sinus disease (ISSD) is
      rare and early management is important. There is no report regarding the results
      of endoscopic sinus surgery (ESS) for prolonged abducens palsy due to ISSD. We
      present four cases of ISSD with solitary abducens palsy that received ESS from
      1995 through 2000. The interval between onset of diplopia and ESS was longer than
      96 hours (range, 4 days to 42 months). The sphenoid lesions were caused by
      Aspergillosis in two patients and inflammation in two. Three patients recovered
      completely from abducens palsy after 4-17 months and had no surgical
      complications. In conclusion, ESS is a safe and effective treatment for ISSD with
      abducens palsy. Recovery from abducens palsy is slow and progressive. Improvement
      of extraocular movement is an early sign of recovery.

PMID- 12518782
TI  - Primary carcinoid tumor of the testis: case report.
AB  - Carcinoid tumor of the testis is exceedingly rare. Most carcinoid tumors occur in
      the appendix or ileocecal region (85%), while others are found in the lung,
      liver, and genitourinary tract (15%). A primary carcinoid testis tumor may
      originate from argentaffin or Kulchitsky's cells, which are located in the
      Lieberkuhn crypt. Preoperative ultrasound may show a solid, hypoechoic, well
      defined margin mass combined with calcification or a cyst. Differential diagnosis
      of the ultrasound appearance is testicular tumor (teratoma/embryonal cell
      carcinoma), epidermoid tumor, tuberculous epididymo-orchitis, and the result of
      trauma. Radical orchiectomy remains the main treatment for a carcinoid testis
      tumor. Grossly, surgical removal of the tumor presents with a solid mass, tan to
      white in color. Immunohistochemical study shows that tumor cells are diffusely
      reactive to antibodies to keratins AE1 and AE3, chromogranin-A, neuron-specific
      enolase (NSE), and synaptophysin. A pure primary testicular carcinoid tumor has
      been treated as a benign lesion, while metastatic carcinoid tumor has a poor
      prognosis regardless of the primary site. To rule out the possibility of
      metastasis resulting from an extra-testicular primary carcinoid, careful and
      thorough postoperative whole body surveys are important. Chest X-ray, chest
      computed tomogram (CT), abdominal and pelvic CT, and octreotide scintigraphy are
      indicated. We herein describe a case of primary carcinoid tumor of the testis and
      review the literature.

PMID- 12518783
TI  - Nutcracker syndrome: an overlooked cause of hematuria.
AB  - Nutcracker syndrome is caused by compression of the left renal vein between the
      aorta and the superior mesenteric artery, where it courses in the fork formed at
      the bifurcation of these arteries. The phenomenon results in left renal venous
      hypertension, which leads to left renal vein and left gonadal vein varices and
      unilateral hematuria. The main presenting symptom is hematuria, with or without
      left flank pain. The disorder is easily missed by routine diagnostic methods. Its
      incidence is likely underestimated. We report on a 25-year-old woman who
      experienced intermittent gross hematuria and left flank pain. The diagnosis of
      nutcracker syndrome was missed initially. Abdominal computed tomography,
      angiography, venography, and magnetic resonance angiography, which were later
      performed, showed that the left renal vein was compressed between the aorta and
      the superior mesenteric artery. The pressure gradient between the left renal vein
      and the inferior vena cava was 6.8 cm H2O. A diagnosis of nutcracker syndrome was
      established. She refused surgery and was lost to follow-up. The diagnosis and
      treatment of nutcracker syndrome are discussed. Magnetic resonance angiography is
      a safe and reliable tool for diagnosing this disorder.

PMID- 12518784
TI  - Microangiopathic hemolytic anemia in a patient with recurrent anal cancer and
      liver metastasis.
AB  - Microangiopathic hemolytic anemia (MAHA) is a late but fatal complication in
      advanced cancers (cancer-associated). It may also appear in complete remission
      after chemotherapy (chemotherapy-related). Mucin-producing adenocarcinoma has
      been extensively studied in relation to this phenomenon. Squamous cell carcinoma
      with MAHA, on the other hand, has not often been reported in the English
      literature. Because of the difficulty of case collection, understanding of the
      association of MAHA and anal squamous cell carcinoma remains vague. We present a
      60-year-old woman with anal cancer and liver metastasis. This patient received
      chemotherapy (mitomycin C, 5-fluoruracil, and cisplatin) and reached a good
      partial response. MAHA developed 2 months later, and tumor recurrence with rapid
      deterioration appeared 5 months later. The patient died 5 months after MAHA was
      diagnosed. We consider that the MAHA in this patient is chemotherapy-related.
      However, the possibility of cancer-associated MAHA could not be excluded.

PMID- 12518785
TI  - Origin of the annual symposium on the biology of skin.

PMID- 12518786
TI  - The changing face of cutaneous biology as seen from the National Institutes of
      Health.
AB  - Over the past 50 y, research in skin biology and diseases has changed
      dramatically. These changes include (i) who is doing the research, from M.D.
      clinician dermatologists to predominantly Ph.D. research scientists and full-time
      or nearly full-time M.D. and M.D.-Ph.D. scientists, (ii) where, from small
      laboratories in the U.S.A. to large laboratories and multiinvestigator
      collaborations worldwide, (iii) what, from a focus on common skin diseases to an
      emphasis on understanding basic processes in skin, both in normal and disease
      states, and (iv) how, from patient observations, histology, and clinical
      immunology to cell and tissue culture, molecular biology and genetics, genomics
      and proteomics. Financing of this research has also changed, from the use of
      clinical surplus funds supplemented by U.S. government (National Institutes of
      Health, Veterans Administration, and other) monies to a greater dependence on
      government and private (pharmaceutical industry and philanthropy) funding. The
      future, funding issues aside, promises great advances with translation of basic
      knowledge to the diagnosis, prevention, and treatment of skin diseases.

PMID- 12518787
TI  - Progress in molecular genetics of heritable skin diseases: the paradigms of
      epidermolysis bullosa and pseudoxanthoma elasticum.
AB  - The 42nd Annual Symposium on the Biology of the Skin, entitled "The Genetics of
      Skin Disease", was held in Snowmass Village, Colorado, in July 1993. That meeting
      presented the opportunity to discuss how modern approaches to molecular genetics
      and molecular biology could be applied to understanding the mechanisms of skin
      diseases. The published proceedings of this meeting stated that "It is an
      opportune time to examine the genetics of skin disease" (Norris et al, 1994).
      Indeed, this meeting just caught the wave of early pioneering studies that have
      helped us to understand the molecular basis of a large number of genodermatoses.
      This overview presented in the 50th Annual Symposium on the biology of the skin,
      highlights the progress made in the molecular genetics of heritable skin diseases
      over the past decade.

PMID- 12518788
TI  - Progress in cutaneous cancer research.
AB  - Cutaneous cancers represent a major public health concern due to the very high
      incidence, associated medical costs, substantial mortality, and cosmetic
      deformities associated with treatment. Considerable progress in basic research
      has provided new insights into the underlying genetic basis of the major human
      cutaneous cancers, malignant melanoma, basal cell carcinoma, and squamous cell
      carcinoma. In turn, these genetic insights have illuminated biochemical pathways
      that promise to provide new approaches to the prevention and treatment of
      cutaneous neoplasms. This review will detail the evolving genetic information and
      indicate how this information is being used to refine experimental models that
      serve to both define the biochemistry of cancer pathogenesis and test novel
      approaches to cancer therapy. Combined with preventive measures to reduce
      exposure to sunlight, these advances are likely to reduce this major public
      health burden in the coming decade.

PMID- 12518789
TI  - Life and death signaling pathways contributing to skin cancer.
AB  - Apoptosis is generally regarded as a critical regulatory event in the development
      of malignancies in several different organ systems (Thompson, 1995). Initially,
      oncologists focused on alterations in rates of proliferation and cell cycle
      kinetics, but more recently an emphasis on apoptosis has dominated the fight
      against cancer (Evan and Vousden, 2001). As approximately 1,000,000 individuals
      in the U.S.A. develop skin cancer each year, it is important to elucidate the
      molecular mechanisms that govern cell survival and cell death in the epidermis
      (Miller and Weinstock, 1994). Moreover, given that most skin cancers occur on sun
      exposed skin, the pro-apoptotic and antiapoptotic response of keratinocytes (KC)
      to UV light is of particular relevance to the development of skin cancer (Brash
      et al, 1996). Whereas both squamous cell carcinoma (SCC) and basal cell carcinoma
      (BCC) arise from epidermal KC, it is becoming increasingly apparent that the
      natural history of their development, their underlying molecular pathogenesis,
      and potential involvement of antiapoptotic pathways are significantly different.
      Nonetheless, as pointed out later in the text, significant progress is being made
      in our understanding of the pathophysiology of these relatively common epithelial
      cell-derived neoplasms. In this review we will explore four topics: first, a
      review of the life and death signaling pathways operative in normal human skin
      that prevents premature apoptosis of KC with an emphasis on nuclear factor kappaB
      (NFkappaB) survival signals; second, the molecular pathways that are engaged and
      regulate apoptosis after normal KC are exposed to ultraviolet (UV) light; third,
      the apoptotic resistant mechanisms that premalignant and malignant KC utilize to
      avoid cell death; fourth, therapeutic strategies that can render malignant cells
      more susceptible to apoptosis with an emphasis on a death pathway mediated by the
      death ligand TRAIL.

PMID- 12518790
TI  - Keratinocyte survival, differentiation, and death: many roads lead to mitogen
      activated protein kinase.
AB  - The epidermis is a dynamic and continually renewing surface that provides and
      maintains a life-sustaining interface with the environment. The epidermal
      keratinocyte, the major cell type of the epidermis, undergoes a complex and
      carefully choreographed program of differentiation. This process requires a
      balance between keratinocyte proliferation, differentiation, and apoptosis. This
      overview will concentrate on cascades that regulate the balance between
      keratinocyte cell proliferation and survival, and apoptosis and cell
      differentiation, with a particular emphasis on the role of the mitogen-activated
      protein kinase cascades. A summary of the literature suggests that extracellular
      regulated kinases function to promote keratinocyte proliferation and survival,
      whereas p38 mitogen-activated protein kinase functions to promote differentiation
      and apoptosis.

PMID- 12518791
TI  - Epidermal differentiation: transgenic/knockout mouse models reveal genes involved
      in stem cell fate decisions and commitment to differentiation.
AB  - Epidermal development and differentiation are similar processes and therefore the
      study of one is likely to provide insight into the other. The signaling cascades
      required for epidermal differentiation are largely unknown. Recent evidence,
      however, has implicated two proteins, p63 and c-Myc, in different stages of
      epidermal development and differentiation. p63 was shown to be required for
      embryonic epidermal development. Mice lacking p63 do not develop stratified
      epithelia and appendages suggesting a role for p63 in the commitment to squamous
      epithelial lineages. Subsequent stem cell fate decisions are required to form the
      different structures of stratified epithelia including hair follicles, sebaceous
      glands, and epidermis. Several genes of the Wnt signaling pathway have been
      implicated in this process, including c-Myc, a downstream target of the Wnt
      pathway. Interestingly, targeted overexpression of c-Myc in the basal layer of
      the epidermis results in an increase in sebaceous gland size and number at the
      expense of hair follicles. This suggests that c-Myc promotes differentiation of
      epidermal stem cells into sebaceous glands. In this review, we discuss
      transgenic/knockout mouse models that have provided evidence linking c-Myc and
      p63 to different stages of epidermal development and differentiation.

PMID- 12518792
TI  - 20 years after--milestones in molecular photobiology.
AB  - Ultraviolet radiation represents one of the most relevant environmental factors
      because of its hazardous health effects, which include induction of skin cancer,
      premature skin aging, and exacerbation of infectious diseases. The biologic
      effects exerted by ultraviolet radiation have been well characterized by a
      variety of in vitro and in vivo studies. The events taking place inside the cell
      during the ultraviolet response, however, remained unclear for quite a long time.
      Molecular photobiology has increased our knowledge about ultraviolet-induced
      signal transduction enormously within the last 10 years. For a long time, nuclear
      DNA has been regarded as the only chromophore for ultraviolet radiation. Today we
      know that ultraviolet radiation can affect also other molecular targets located
      in the cytoplasm and at the cell membrane. These targets include cell surface
      receptors, kinases, phosphatases, and transcription factors. Detailed knowledge
      about ultraviolet-induced signal transduction will certainly increase our
      understanding of how ultraviolet radiation exerts its biologic effects and
      furthermore will provide us with tools to interfere with these pathways, thereby
      reducing the adverse effects of ultraviolet radiation.

PMID- 12518793
TI  - Fifty years of skin aging.
AB  - In developed countries, interest in cutaneous aging is in large part the result
      of a progressive, dramatic rise over the past century in the absolute number and
      the proportion of the population who are elderly (Smith et al, 2001). The
      psychosocial as well as physiologic effects of skin aging on older individuals
      have created a demand for better understanding of the process and particularly
      for effective interventions. Skin aging is a complex process determined by the
      genetic endowment of the individual as well as by environmental factors. The
      appearance of old skin and the clinical consequences of skin aging have been well
      known for centuries, but only in the past 50 y have mechanisms and mediators been
      systematically pursued. Still, within this relatively short time there has been
      tremendous progress, a progress greatly enhanced by basic gerontologic research
      employing immunologic, biochemical, and particularly molecular biologic
      approaches (Figs 1, 2).

PMID- 12518794
TI  - A possible role of keratinocytes of skin and mucous membranes in prion
      propagation and transmission.
AB  - Prion diseases or transmissible spongiform encephalopathies are lethal
      neurodegenerative diseases caused by proteinaceous agents that consist of an
      abnormal form of a host protein designated PrP and are devoid of nucleic acids.
      In laboratory settings these diseases are usually transmitted by intracerebral or
      peripheral inoculation. In the field they have been shown to be transmitted by
      uptake of contaminated food but in most instances the route of transmission
      remains obscure. Both nervous and lymphatic tissues in peripheral organs have
      been implicated in the spread and propagation of prions. The exact sites of
      uptake and initial propagation of the infectious agents have not yet been
      determined, however. As the expression of PrPc is required for the propagation of
      the infectious agent the search for peripheral cells positive for PrPc may reveal
      potential routes of entry and transmission. Recently epidermal and mucosal
      keratinocytes have been found to express PrPc. These data together with the
      recent finding that epithelial cells are able to support prion replication in
      vitro suggest that keratinocytes might play a role in the pathogenesis and/or
      transmission of prion diseases.

PMID- 12518795
TI  - Optical non-invasive approaches to diagnosis of skin diseases.
AB  - A number of noninvasive approaches have been developed over the years to provide
      objective evaluation of the skin both in health and in disease. The advent of
      computers, as well as of lasers and photonics, has made it possible to develop
      additional techniques that were impossible a few years ago. These approaches
      provide the dermatologist with sensitive tools to measure the skin's condition in
      terms of physiologic parameters (e.g., color, erythema and pigmentation,
      induration, sebaceous and stratum corneum lipids, barrier function, etc.). Yet, a
      typical dermatologic diagnosis relies primarily on the trained eyes of the
      physician and to a lesser extent on information from other senses, such as touch
      and smell. The trained senses of the dermatologist backed by his/her brain form a
      powerful set of tools for evaluating the skin. The golden rule in diagnosis
      remains the histologic examination of a skin biopsy, a rather invasive method.
      These tools have served the profession well. The advent of ever faster and
      cheaper computers and of sensitive, inexpensive optical instrumentation of
      minimal dimensions provides the professional with the possibility of making
      objective measures of a number of skin parameters.

PMID- 12518796
TI  - Ribozyme therapeutics.
AB  - Since their initial discovery, ribozymes have shown great promise not just as a
      tool in the manipulation of gene expression, but also as a novel therapeutic
      agent. This review discusses the promises and pitfalls of ribozyme technology,
      with a special emphasis on cancer-related applications, though relevance to skin
      disease will also be discussed.

PMID- 12518797
TI  - The potential of metabolic interventions to enhance transdermal drug delivery.
AB  - The stratum corneum is a complex tissue that is metabolically active, and
      undergoes dynamic structural modifications due to the presence of several self
      regulating enzymatic systems. A large number of defensive (protective) functions
      are embodied in this tissue, each with its own structural and biochemical basis.
      Moreover, the stratum corneum is responsive to external perturbations to the
      permeability barrier, upregulating a variety of metabolic processes aimed at
      restoring normal barrier function. Traditional drug delivery methods, which are
      of limited effectiveness, view the stratum corneum as a static, but semipermeable
      membrane. In contrast, newer metabolically based methods, which can be deployed
      alone, or in conjunction with standard methods, have been shown to expand the
      spectrum of drugs that can be delivered transdermally in hairless mouse
      epidermis. Yet, while these new approaches hold great promise, if equally
      effective in human skin, they pose new questions about the risks of a highly
      permeabilized stratum corneum.

PMID- 12518798
TI  - Matrix molecular weight cut-off for encapsulation of carbonic anhydrase in
      polyelectrolyte beads.
AB  - The enzyme bovine carbonic anhydrase (BCA) has been immobilized in the chitosan
      alginate system for the first time, to catalyze the conversion of CO2 to HCO3-.
      Chitosan-coated alginate beads are a biodegradable and environmentally benign
      matrix, chosen for application of the enzyme in a novel biomimetic CO2
      sequestration system. The feasibility of the system and immobilization of the
      enzyme were demonstrated in our earlier studies. Optimization of the matrix to
      improve the retention time of the enzyme in an encapsulated form is the subject
      of the present study. The improvement in the molecular weight cut-off of the
      beads was accomplished by adjusting the cross-linking conditions, coating
      composition, and molecular weight of the system. The quantity of enzyme released
      from the system was measured by a Bio-Rad protein assay. Poly-L-lysine was also
      used as a coating reagent for comparison purposes. The presence of a coating on
      the alginate beads was verified by Kjeldahl analyses. The difference in the
      microstructures of alginate and chitosan/alginate beads was demonstrated by SEM
      studies. Mineralization of the chitosan/alginate matrix in the presence of CaCO3
      was also studied by FT-IR, to assess the possibility of using the beads
      continuously in a bioreactor.

PMID- 12518799
TI  - Growth of various cell types in the presence of lactic and glycolic acids: the
      adverse effect of glycolic acid released from PLAGA copolymer on keratinocyte
      proliferation.
AB  - Poly(alpha-hydroxy-acid)s derived from lactic acid (LA) and glycolic acid (GA)
      are bioresorbable polymers that are currently used in human surgery and in
      pharmacology to make temporary therapeutic devices. Nowadays, increasing
      attention is paid to these polymers in the field of tissue engineering. However,
      the literature shows that a large number of factors can affect many of their
      properties and the responses of biological systems. As part of our investigation
      of the biocompatibility of degradable aliphatic polyesters, the effects of LA and
      GA on the proliferation of various cells under in vitro cell culture conditions
      were studied. The release of LA and GA from films made of a copolymer synthesized
      by the zinc lactate method and composed of 37.5% L-lactyl, 37.5% D-lactyl, and
      25% glycolyl repeating units was first investigated over a period of 30 days
      under abiotic conditions in a cell culture medium in order to identify a range of
      acid concentrations consistent with releases to be expected in real cell
      cultures. Four cell lines, namely 3T3-J2, C3H10(1/2), A431, and HaCat, and three
      primary cell cultures, namely rat endothelial cells, rat smooth muscle cells, and
      human dermal fibroblasts, were then allowed to grow in the presence of LA and GA
      at various concentrations taken within the selected 10-1000 mg/cm3 range. Little
      or no effect was observed on the proliferation of all cells except human
      keratinocytes, whose growth was dramatically inhibited by GA at concentrations as
      low as 10 mg/cm3. The inhibiting effect of GA was confirmed by considering the
      growth of keratinocytes on films made of the same copolymer, in comparison with
      poly(DL-lactic acid) and polystyrene taken as references. This work shows that GA
      releasing degradable matrices are not adapted to the culture of keratinocytes
      with the aim of making skin grafts.

PMID- 12518800
TI  - Cytotoxicity evaluation of gelatin sponges prepared with different cross-linking
      agents.
AB  - Gelatin is a natural polymer used in pharmaceutical and medical applications,
      especially in the production of biocompatible and biodegradable wound dressings
      and drug delivery systems. Gelatin granules hydrate, swell and solubilize in
      water, and rapidly degrade in vivo. The durability of these materials could,
      however, be prolonged by cross-linking by aldehydes, carbodiimides, and aldose
      sugars, but the biocompatibility of collagenous biomaterials is profoundly
      influenced by the nature and extent of cross-linking. In this study, gelatin
      sponges were prepared by using various cross-linkers such as glutaraldehyde (GA),
      1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDAC), and D
      fructose. The effects of the type and the amount of cross-linker on thermal and
      mechanical properties, stability, and cytotoxicity were investigated. The
      mechanical analysis data showed that an increase in the amount of GA in the
      sponge structures caused a slight increase in the modulus of elasticity but had
      almost no effect on the tensile strength. Increase in the EDAC concentration
      produced a maximum in the modulus of elasticity and tensile strength values. The
      stability of the sponges and the time required for complete degradation in
      aqueous media increased in parallel with the cross-linker content. In vitro
      studies carried out with fibroblast cells demonstrated a higher cell viability
      for the samples cross-linked with low concentrations of GA than for those cross
      linked with EDAC.

PMID- 12518801
TI  - In vitro study of drug-loaded bioresorbable films and support structures.
AB  - Bioresorbable films can serve simultaneously as anatomic support structures and
      as drug delivery platforms. In the present study, bioresorbable poly(L-lactic
      acid) (PLLA) films containing dexamethasone were prepared by solution processing
      methods. Their in vitro studies focused on the mechanical properties with respect
      to morphology and degradation and erosion processes. Novel expandable support
      devices (stents) developed from these films were studied. Such a stent would
      support conduits, such as the neonatal trachea to treat tracheal malacia, until
      the airway matures, and would then be totally resorbed, obviating the need for a
      removal operation. The PLLA films showed good initial mechanical properties. They
      can accommodate drug incorporation on the film surface and also in the bulk.
      Water incubation of the films results in a decrease in their tensile mechanical
      properties, due to chain scission and morphological changes. These changes can
      vary from degradation and small changes in morphological features to erosion,
      leading to a microporous structure, depending on the polymer. The cumulative
      release of dexamethasone from the films is linear. The rate of release is
      determined by the film's structure (drug location/dispersion). The stents
      demonstrated good mechanical properties. The initial radial compression strength
      of the stent is determined mainly by the polymer structure. Drug incorporation
      has a minor effect on the initial stent strength. Exposure to radial compression
      stress results in elastic reversible deformation or a sudden brittle fracture,
      depending on the polymer. A 20-week in vitro study of the stents showed that they
      are applicable for supporting body conduits, such as the trachea.

PMID- 12518802
TI  - Composite poly(lactide)/hydroxylapatite screws for fixation of osteochondral
      osteotomies. A morphometric, histologic and radiographic study in sheep.
AB  - The aim of this study was to evaluate the healing of an osteochondral fragment
      created in the distal sheep femur in response to fixation with a biodegradable
      polylactide/hydroxylapatite composite screw. Poly(L-lactide) screws were used for
      comparison. At follow-up times of 4 and 8 weeks, the specimens were examined with
      standard radiography and computed tomography, as well as with macro- and micro
      histomorphometry. The intact contralateral femur served as a control. Only
      minimal signs of degradation of the polymer could be seen in the histologic
      specimens. At 8 weeks, nearly all osteotomies had healed completely and an
      association between implant type and delayed osteotomy healing was found. The
      width of the repair tissue at the tissue-implant interface was 250 +/- 48 microm,
      representing a clear transition zone of newly formed trabecular bone separating
      the implant from the surrounding plexiform bone. This study showed that large
      polylactide implants which are buffered with hydroxylapatite show benign tissue
      responses and good implant osteointegration. The osteotomy healing in a weight
      bearing osteochondral fragment model in sheep utilizing a composite
      polylactide/hydroxylapatite screw was equivalent to a similar polylactide screw
      implant, indicating that hydroxylapatite-buffered screw implants could be used
      for similar indications in current clinical use.

PMID- 12518803
TI  - pH-modulated release of insulin entrapped in a spontaneously formed hydrogel
      system composed of two water-soluble phospholipid polymers.
AB  - To develop a polypeptide drug carrier through oral administration, a polymer
      hydrogel has been found that is very easy to prepare by mixing two water-soluble
      phospholipid polymers. The polymers having 2-methacryloyloxyethyl
      phosphorylcholine (MPC) moieties spontaneously formed a hydrogel, which showed
      controllable dissociation via pH changes. In this study, the MPC polymer hydrogel
      was prepared from aqueous solutions containing water-soluble poly[MPC-co
      methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB),
      and the applicability of the hydrogel as an oral drug delivery carrier was
      examined. The gelation process from the two MPC polymers is spontaneous,
      requiring no chemical reactions and/or no physical stimuli. PMB has a hydrophobic
      domain, which is suitable for loading hydrophobic drugs. Insulin could be very
      easily loaded to almost 100% in the hydrogel. PMA also has carboxyl groups, which
      are well known for pH sensitivity. At pH 1.8, the swelling continued for 8 h,
      with complete dissociation after 16 h. At pH 6.8, the hydrogel completely
      dissociated within 4 h. The hydrogel remained stable at pH 1.8 and released all
      the insulin at pH 6.8. The release rate was approximately four times faster at pH
      6.8. After release, the insulin did not show any denaturing tendency.

PMID- 12518804
TI  - Synthesis and characterization of pH-sensitive glycopolymers for oral drug
      delivery systems.
AB  - pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic
      peptides and proteins, due to their ability to respond to environmental pH
      changes. New pH-sensitive glycopolymers have been developed by free-radical
      photopolymerization of methacrylic acid and 2-methacryloxyethyl glucoside, using
      tetra(ethylene glycol) dimethacrylate as a cross-linking agent. To determine the
      suitability of these hydrogels as carriers for oral drug delivery devices, their
      swelling behavior was investigated as a function of the pH and copolymer
      compositions, and various structural parameters such as the number-average
      molecular weight between cross-links, Mc, the mesh size, xi, and the cross
      linking density, rho(x), were calculated. The transition between the swollen and
      the collapsed states of these hydrogels was at a pH of 5. The swelling ratios of
      the hydrogels increased at pH values above 5. The mesh sizes of the hydrogels
      were between 18 and 35 A in the collapsed state (at pH 2.2) and between 70 and
      111 A in the swollen state (at pH 7.0). Finally, as the cross-linking ratio of
      the copolymer increased, the swelling ratio of the hydrogels decreased at both pH
      2.2 and 7.0.

PMID- 12518805
TI  - Longitudinal relations among parental emotional expressivity, children's
      regulation, and quality of socioemotional functioning.
AB  - The role of regulation as a mediator of the relations between maternal emotional
      expressivity and children's adjustment and social competence was examined when
      children (N = 208) were 4.5 to just 8 years old (Time 1, T1) and 2 years later
      (Time 2, T2). At T2, as at T1, regulation mediated the relation between positive
      maternal emotional expressivity and children's functioning. When T1 relations and
      the stability of variables over time were controlled for in a structural equation
      model, T2 relations generally were nonsignificant, although parents' dominant
      negative expressivity predicted high regulation. In contrast, in regressions, the
      findings for parent positive expressivity, but not negative expressivity, held at
      T2 when T1 variables were controlled. Thus, relations for negative expressivity,
      but not positive expressivity, changed with age.

PMID- 12518806
TI  - Children with lesbian parents: a community study.
AB  - Existing research on children with lesbian parents is limited by reliance on
      volunteer or convenience samples. The present study examined the quality of
      parent-child relationships and the socioemotional and gender development of a
      community sample of 7-year-old children with lesbian parents. Families were
      recruited through the Avon Longitudinal Study of Parents and Children, a
      geographic population study of 14,000 mothers and their children. Thirty-nine
      lesbian-mother families, 74 two-parent heterosexual families, and 60 families
      headed by single heterosexual mothers were compared on standardized interview and
      questionnaire measures administered to mothers, co-mothers/fathers, children, and
      teachers. Findings are in line with those of earlier investigations showing
      positive mother-child relationships and well-adjusted children.

PMID- 12518807
TI  - Parent-child conversations about science: the socialization of gender inequities?
AB  - This study investigated the family as a context for the gender typing of science
      achievement. Adolescents (N = 52) from 2 age levels (mean ages = 11 and 13 years)
      participated with their mothers and fathers on separate occasions; families were
      from predominantly middle-income European American backgrounds. Questionnaires
      measured the parents' and the child's attitudes. Each parent also engaged his or
      her child in 4 structured teaching activities (including science and nonscience
      tasks). There were no child gender or grade-level differences in children's
      science-related grades, self-efficacy, or interest. However, parents were more
      likely to believe that science was less interesting and more difficult for
      daughters than sons. In addition, parents' beliefs significantly predicted
      children's interest and self-efficacy in science. When parents' teaching language
      was examined, fathers tended to use more cognitively demanding speech with sons
      than with daughters during one of the science tasks.

PMID- 12518808
TI  - The formation of in-group favoritism and out-group prejudice in young children:
      are they distinct attitudes?
AB  - Although standardized measures of prejudice reveal high levels of ethnocentric
      bias in the preschool years, it may reflect in-group favoritism or out-group
      prejudice. A measure that partially decouples the two attitudes was given to
      White children between 4 and 7 years of age to examine the reciprocal relation
      between and the acquisition and correlates of in-group and out-group attitudes.
      The two attitudes were reciprocally correlated in 1 sample from a racially
      homogeneous school but not in a 2nd sample from a mixed-race school. In-group
      favoritism did not appear until 5 years of age but then reached significant
      levels; it was strongly related to developing social cognitions. Out-group
      prejudice was weaker, but its targets suffer from comparison with the high
      favoritism accorded in-group members.

PMID- 12518809
TI  - Looking and search measures of object knowledge in preschool children.
AB  - The same preschoolers were tested on an observation task and a search task
      involving the invisible displacement of an object. In the observation task,
      children watched an object roll behind a screen from which protruded the top of a
      solid wall. Analyses revealed significantly longer looking to impossible than to
      possible outcomes in all children. In search, the child was allowed to retrieve
      the rolled object. Most 3-year-olds but significantly fewer 2.5-year-olds
      completed the search successfully. An unexpected sex difference was found, with
      boys outperforming girls. Search performance was not associated with observation
      measures. The findings indicate that children visually discriminate violations of
      solidity but that this sensitivity is not associated with successful search
      performance.

PMID- 12518810
TI  - Adolescents' reasoning about exclusion from social groups.
AB  - Ninth- and 11th-grade students (N = 379) were surveyed regarding their
      evaluations of excluding someone from a social group solely on the basis of his
      or her social reference group membership. Individuals evaluated exclusion in
      ambiguous and nonambiguous situations. Judgments and reasoning about exclusion
      were compared with judgments and reasoning about a more prototypically moral
      situation (denial of resources). Overall, participants evaluated exclusion as
      less wrong than denial of resources and used fewer moral and more conventional
      reasons to justify their judgments. Participants relied more on their group
      knowledge or stereotypes in evaluating ambiguous situations and more on their
      personal knowledge in evaluating nonambiguous situations. Age- and gender-related
      differences in evaluations, reasoning, and use of stereotypes were also found.

PMID- 12518811
TI  - Testosterone and child and adolescent adjustment: the moderating role of parent
      child relationships.
AB  - In a sample of established middle- and working-class families with normally
      developing children and adolescents ranging in age from 6 to 18 years, sons' and
      daughters' testosterone levels showed little direct connection to risk behavior
      or symptoms of depression. In contrast, testosterone's positive relation with
      risk behavior and negative relation with depression were conditional on the
      quality of parent-child relations. As parent-child relationship quality
      increased, testosterone-related adjustment problems were less evident. When
      relationship quality decreased, testosterone-linked risk-taking behavior and
      symptoms of depression were more in evidence. Few relations were found between
      parents' testosterone and child behavior. Boys' and girls' ages and stages of
      pubertal development were important for understanding the expression of hormone
      related problem behavior in some cases but not in others.

PMID- 12518812
TI  - The role of the shared family context in differential parenting.
AB  - This article examines the role of the shared family context in understanding
      differential parental treatment of children. Child-specific and family-context
      predictors of differential parental positivity and negativity were examined using
      multilevel modeling in a population of 8,476 children nested in 3,762 families.
      Child age was the strongest child-specific predictor of positivity and
      differential positivity. Lower socioeconomic status (SES), marital
      dissatisfaction, and larger family size were associated with higher levels of
      differential positivity. There was evidence of potentiation when risks were
      combined. Children's temperament was associated with parental negativity and
      differential negativity. The strength of this association was moderated by SES.
      Mixed-gender sibships in families with marital dissatisfaction and children in
      single-parent families received the highest levels of differential negativity.
      The findings are discussed in the context of shared and nonshared environmental
      influences on development.

PMID- 12518813
TI  - A closer look at preschoolers' freely produced labels for facial expressions.
AB  - Children's performance on free labeling of prototypical facial expressions of
      basic emotions is modest and improves only gradually. In 3 data sets (N = 80,
      ages 4 or 5 years; N = 160, ages 2 to 5 years; N = 80, ages 3 to 4 years), errors
      remained even when method factors (poor stimuli, unavailability of an appropriate
      label, or the difficulty of a production task) were controlled. Children's use of
      emotion labels increased with age in a systematic order: Happy, angry, and sad
      emerged early and in that order, were more accessible, and were applied broadly
      (overgeneralized) but systematically. Scared, surprised, and disgusted emerged
      later and often in that order, were less accessible, and were applied narrowly.

PMID- 12518814
TI  - Behavioral reputation: a cross-age perspective.
AB  - This study examined the measurement of peer perceptions of behavioral reputation
      within the contexts of elementary, middle, and high school environments (Grades 2
      12, N = 2,812) through the systematic evaluation of the psychometric properties
      of the Revised Class Play (A. S. Masten, P. Morison, & D. S. Pellegrini, 1985).
      Confirmatory factor analyses demonstrated that the data did not fit A. S. Masten
      et al.'s original 3-factor structure. Cross-loading of items and different
      patterns of association between subscales across age groups (elementary, middle,
      and high school) contributed to the overall poor fit. Exploratory factor analyses
      revealed an alternative 4-factor structure as a more reliable and valid means of
      assessing behavioral reputation regardless of the age of the peer group sampled.
      Both convergent and divergent patterns of associations emerged across
      developmental levels.

PMID- 12518815
TI  - TV guide: two-year-old children learn to use video as a source of information.
AB  - Learning to use symbols is a challenge for young children even when the symbol in
      question (e.g., a live video image) is iconic and seems transparent to adults.
      This research examined the effect of experience on children's use of video
      presented information. Two-year-old children saw themselves "live" on their
      family television for 2 weeks and then participated in an object-retrieval task.
      The children reliably used a live video presentation of an adult hiding a toy in
      an adjoining room to find the toy. Most also transferred what they learned to a
      task involving another symbol (pictures) that typically is very difficult for
      this age group. The results reveal flexibility in 2-year-olds' symbol use that
      follows from successful representation of a symbolic relation.

PMID- 12518816
TI  - Development of an abstract category representation for the spatial relation
      between in 6- to 10-month-old infants.
AB  - Nine experiments examined the formation of an abstract category representation
      for the spatial relation between by 6- to 10-month-old infants. The experiments
      determined that 9- to 10-month-olds, but not 6- to 7-month-olds, could form an
      abstract category representation for between when performing in an object
      variation version of the between categorization task. The results also
      demonstrated that 6- to 7-month-olds could form category representations for
      between in the object-variation version of the between categorization task but
      that such representations were specific to the particular objects presented. The
      evidence confirms that representations for different spatial relations emerge at
      different points during development, and suggests that each representation
      undergoes its own period of development from concrete to abstract.

PMID- 12518817
TI  - Predicting preschoolers' externalizing behaviors from toddler temperament,
      conflict, and maternal negativity.
AB  - Rarely have researchers elucidated early childhood precursors of externalizing
      behaviors for boys and girls from a normative sample. Toddlers (N = 104; 52
      girls) were observed interacting with a same-sex peer and their mothers, and
      indices of conflict-aggression, emotion and behavior dysregulation, parenting,
      and child externalizing problems were obtained. Results indicated that boys
      initiated more conflictual-aggressive interactions as toddlers and had more
      externalizing difficulties 2 years later, yet girls' (not boys') conflict
      aggressive initiations at age 2 were related to subsequent externalizing
      problems. When such initiations were controlled for, emotional-behavioral
      undercontrol at age 2 also independently predicted externalizing problems at age
      4. Moreover, the relation between conflict-aggressive initiations at age 2 and
      externalizing problems at age 4 was strongest for dysregulated toddlers. Finally,
      the relation between age 2 conflict-aggressive initiations and age 4
      externalizing problems was strongest for those toddlers who incurred high levels
      of maternal negativity. These findings illustrate temperament by parenting
      connections in the development of externalizing problems.

PMID- 12518818
TI  - Diffractive axicons in oblique illumination: analysis and experiments and
      comparison with elliptical axicons.
AB  - Axicons in oblique illumination produce broadened focal lines, a problem, e.g.,
      in scanning applications. A compact mathematical description of the focal segment
      is presented, for the first time, to our knowledge, and the results are compared
      with elliptical axicons in normal illumination. In both cases, analytical
      expressions in the form of asteroid curves are obtained from asymptotic wave
      theory and caustic surfaces. The results are confirmed by direct diffraction
      simulations and by experiments. In addition we show that at a fixed angle an
      elliptical axicon can be used to compensate for the adverse effects of oblique
      illumination.

PMID- 12518819
TI  - Phase grating design for a dual-band snapshot imaging spectrometer.
AB  - Infrared spectral features have proved useful in the identification of threat
      objects. Dual-band focal-plane arrays (FPAs) have been developed in which each
      pixel consists of superimposed midwave and long-wave photodetectors [Dyer and
      Tidrow, Conference on Infrared Detectors and Focal Plane Arrays (SPIE,
      Bellingham, Wash., 1999), pp. 434-440]. Combining dual-band FPAs with imaging
      spectrometers capable of interband hyperspectral resolution greatly improves
      spatial target discrimination. The computed-tomography imaging spectrometer
      (CTIS) [Descour and Dereniak, Appl. Opt. 34, 4817-4826 (1995)] has proved
      effective in producing hyperspectral images in a single spectral region. Coupling
      the CTIS with a dual-band detector can produce two hyperspectral data cubes
      simultaneously. We describe the design of two-dimensional, surface-relief,
      computer-generated hologram dispersers that permit image information in these two
      bands simultaneously.

PMID- 12518820
TI  - Holographic recording of Bragg gratings for wavelength division multiplexing in
      doped and partially polymerized poly(methyl methacrylate).
AB  - Bragg gratings are recorded in doped and partially polymerized poly(methyl
      methacrylate) with green light (wavelength, 532 nm) in transmission geometry, and
      the gratings are read in reflection geometry with infrared light (wavelength,
      approximately 1550 nm). Diffraction efficiencies of more than 99% with a
      wavelength bandwidth of approximately 1 nm are obtained for single gratings with
      a typical length of 15 mm. Superposition of four gratings in a volume sample has
      been demonstrated as well. The material is promising for use in the fabrication
      of add-drop filters, attenuators, switches, and multiplexers-demultiplexers for
      optical networks that use wavelength division multiplexing.

PMID- 12518821
TI  - Optimization of azimuth angle settings in polarizer-compensator-sample-analyzer
      off-null ellipsometry.
AB  - The dependence of the azimuth angle settings on the change in off-null intensity
      of a polarizer-compensator-sample-analyzer ellipsometer owing to changes in
      sample properties is studied. First, a closed-form expression for the
      relationship between azimuth angles that fulfill the null condition is presented.
      An approximation for the off-null light intensity near null that is valid for
      small changes of the p- and s-reflection coefficients of an isotropic sample is
      then derived. This approximation shows that the intensity change near the null
      can be described by changes in the ellipsometric parameters tan phi and A only.
      Expressions for finding the azimuth angle that gives the maximum possible
      intensity change for a given change in the sample parameters are also derived.
      The importance of optimization of azimuth angle settings for different samples is
      investigated and found to depend on tan psi. Numerical and experimental results
      chosen from the investigation of gas sensors based on porous silicon are included
      to verify the approximations as well as the optimization.

PMID- 12518822
TI  - Compact optical smoke sensor that uses an integrating cylinder.
AB  - We report a new kind of compact and portable optical smoke sensor that uses an
      integrating cylinder as the light collector. Theoretical analysis shows that this
      smoke sensor can have high sensitivity and good linearity because a number of
      reflected lights participate in the measurement of smoke concentration. A smoke
      sensor has been constructed, and it has demonstrated improved sensitivity and
      linearity compared with the conventional direct-beam-based smoke sensor. Good
      agreement of theoretical and experimental results has been obtained.

PMID- 12518823
TI  - Holographic common-path interferometer for angular displacement measurements with
      spatial phase stepping and extended measurement range.
AB  - A novel technique for extending the unambiguous measurement range for
      differential measurements of angular deflections is presented. The technique
      utilizes a common-path interferometer that simultaneously probes the out-of-plane
      displacement of three points on the object surface. The system is based on a
      single laser diode, and all the optical functions of the system are implemented
      in a dedicated holographic optical element (HOE). The HOE automatically provides
      spatially phase-stepped interference signals for real-time phase measurement. It
      is therefore not necessary to employ any polarizing optics or active elements to
      introduce the phase stepping. The common-path scheme combined with the HOE
      provides a system that is inherently stable, since the HOE operates as both
      transmitter and receiver in the system. The system is compact, is robust, and has
      the potential for being mass-produced at a low cost and is thus well suited for
      industrial use, such as in commercial vibrometers. The technique is demonstrated
      in a system for measuring angular deflections of a plane mirror. The technique,
      however, is not restricted to this use alone and can easily be configured to
      probe other types of surface displacements, e.g., the deflection of a diaphragm.
      In the present configuration, the system can measure angular deflections with a
      sensitivity of 2.5 x 10(-7) rad over a measurement range that is approximately
      3.5 x 10(-3) rad, i.e., a dynamic range of approximately 1:14,000. Furthermore,
      the system can easily be reconfigured for a desired angular sensitivity and
      measurement range.

PMID- 12518824
TI  - Double sinusoidal phase-modulating distributed-Bragg-reflector laser-diode
      interferometer for distance measurement.
AB  - A previously proposed double sinusoidal phase-modulating (DSPM) laser-diode
      interferometer measures distances larger than a half-wavelength by detecting
      modulation depth. Although it requires a vibrating mirror to provide the second
      modulation to the interference signal, such vibrations naturally affect
      measurement accuracy. We propose a static-type DSPM laser-diode interferometer
      that uses no mechanical modulation. Our experimental results indicate a
      measurement error of +/- 1.6 microm.

PMID- 12518825
TI  - Interferometric sensor based on coherent imaging of gratings.
AB  - A sensitive interferometric sensor scheme that is based on coherent imaging of a
      first phase grating onto a second phase grating, their periods accurately
      matched, is suggested. Experimental data, obtained with a setup based on the
      suggested scheme, are presented. The sensor was found capable of measuring an
      angular tilt of a mirror less than 0.5 microrad. Compared with a previously
      suggested measuring scheme, the novelty of the one presented here is the
      inclusion of a second set of gratings, which eliminates measurement ambiguity.
      Some characteristics of the sensor scheme are discussed.

PMID- 12518826
TI  - Analytical modeling of the white-light fringe.
AB  - An analytical technique for extracting phase, visibility, and amplitude
      information as needed for interferometric astrometry for the Space Interferometry
      Mission (SIM) is presented. This model accounts for a number of physical and
      instrumental effects and is valid for the general case of a bandpass filter. I
      was able to obtain a general solution for polychromatic phasors and to address
      the properties of unbiased fringe estimators in the presence of noise. For
      demonstration purposes I studied a rectangular bandpass filter with two different
      methods of optical path difference (OPD) modulation: stepping and ramping OPD
      modulation. A number of areas for further studies relevant to instrument design
      and simulations are outlined and discussed.

PMID- 12518827
TI  - Phase-shift-locked interferometer with a wavelength-modulated laser diode.
AB  - A phase-shift-locked interferometer has been constructed for distance
      measurement. A phase shift produced by sawtooth-current modulation of a laser
      diode is locked to a phase difference preset by polarization optics that consists
      of a quarter-wave plate and polarizers through an electrical feedback technique.
      An optical path difference can be measured from the locked sawtooth-wave current
      amplitude in real time. The sensitivity of the interferometer is discussed.

PMID- 12518828
TI  - Design of an ultralight and compact projection lens.
AB  - Driven by the need for lightweight head-mounted displays, we present the design
      of an ultralight and compact projection lens for a head-mounted projective
      display (HMPD). An HMPD consists of a pair of miniature projection lenses, beam
      splitters, and miniature displays mounted on the helmet and retroreflective
      sheeting materials placed strategically in the environment. The HMPD has been
      proposed recently as an alternative modality for three-dimensional visualization.
      After demonstrating the concept, building a first-generation custom-designed
      prototype, and investigating perception issues and application potentials, we
      designed an ultralight and compact projective lens with a diffractive optical
      element (DOE), plastic components, and aspheric surfaces for the next-generation
      prototype. The key contribution here lies in the conception, optimization, and
      assessment of the projection optics. Thus a brief review of the HMPD technology
      and related research is followed by a detail discussion of the conception and
      optimization of the ultralight and high-performance projection optics. The design
      of the DOE will be particularly described in detail. Finally, the diffraction
      efficiency of the DOE will be evaluated, and the overall performance of the
      optics will be assessed in both object space for the optical designer and visual
      space for possible end-users of the technology.

PMID- 12518829
TI  - Antireflective silica thin films with super water repellence via a solgel
      process.
AB  - A solgel process was developed, through which silica films possessing both high
      antireflection and super water repellence were obtained. In this process, methyl
      modified SiO2 sols synthesized by colloidal suspension of SiO2 particles and
      hexamethyldisilazane (HMDS) were used to deposit spinning-coating films on
      optical glass substrates. On the resultant films the contact angle for water
      increased with the increasing amount of HMDS in the reaction mixture. The biggest
      contact angle was 165 degrees, and the lowest reflectivity on one-sided film
      reached 0.03%. The antireflections were high all the while. One advantage of this
      process is that neither a roughened surface nor fluoroalkyltrialkoxylsilane (FAS)
      is needed to obtained super water repellence.

PMID- 12518830
TI  - Phosphorescence lifetime imaging in turbid media: the forward problem.
AB  - An adequate description of the propagation of near-infrared light in highly
      scattering media is important for imaging hidden luminescent inhomogeneities in
      tissues. We present an improved approach to modeling of the forward problem based
      on a telegraph equation. The asymptotic solutions of the telegraph equation are
      derived and analyzed. The expression for the mean photon path length is also
      obtained.

PMID- 12518831
TI  - In vivo determination of local skin optical properties and photon path length by
      use of spatially resolved diffuse reflectance with applications in laser Doppler
      flowmetry.
AB  - Methods for local photon path length and optical properties estimation, based on
      measured and simulated diffuse reflectance within 2 mm from the light source, are
      proposed and evaluated in vivo on Caucasian human skin. The accuracy of the
      methods was good (2%-7%) for path length and reduced scattering but poor for
      absorption estimation. Reduced scattering and absorption were systematically
      lower in the fingertip than in the forearm skin (633 nm). A maximum intrasite and
      interindividual variation of approximately 35% in an average photon path length
      was found. The methodology was applied in laser Doppler flowmetry, where path
      length normalization of the estimated perfusion removed the optical property
      dependency.

PMID- 12518832
TI  - Multiwavelength three-dimensional near-infrared tomography of the breast: initial
      simulation, phantom, and clinical results.
AB  - Three-dimensional (3D), multiwavelength near-infrared tomography has the
      potential to provide new physiological information about biological tissue
      function and pathological transformation. Fast and reliable measurements of
      multiwavelength data from multiple planes over a region of interest, together
      with adequate model-based nonlinear image reconstruction, form the major
      components of successful estimation of internal optical properties of the region.
      These images can then be used to examine the concentration of chromophores such
      as hemoglobin, deoxyhemoglobin, water, and lipids that in turn can serve to
      identify and characterize abnormalities located deep within the domain. We
      introduce and discuss a 3D modeling method and image reconstruction algorithm
      that is currently in place. Reconstructed images of optical properties are
      presented from simulated data, measured phantoms, and clinical data acquired from
      a breast cancer patient. It is shown that, with a relatively fast 3D inversion
      algorithm, useful images of optical absorption and scatter can be calculated with
      good separation and localization in all cases. It is also shown that, by use of
      the calculated optical absorption over a range of wavelengths, the oxygen
      saturation distribution of a tissue under investigation can be deduced from
      oxygenated and deoxygenated hemoglobin maps. With this method the reconstructed
      tumor from the breast cancer patient was found to have a higher oxy-deoxy
      hemoglobin concentration and also a higher oxygen saturation level than the
      background, indicating a ductal carcinoma that corresponds well to histology
      findings.

PMID- 12518833
TI  - The post anesthesia care unit experience: a family-centered approach.
AB  - The Post Anesthesia Care Unit (PACU) visitation program of Memorial Sloan
      Kettering Cancer Center needed revision. The process was disorganized, visits
      were unescorted, and nurses and physicians were resistant. A committee was formed
      with the goal of developing a new unit philosophy and improving the overall
      process. Committee steps included reviewing the literature, educating staff about
      the benefits of visitation, empowering nurses to incorporate family visitation
      into patient care, and providing family education. As a result, staff attitudes
      changed, and nurses now contact the family within 90 minutes of the patient's
      arrival to the PACU to develop an individualized visitation plan. Morale is high,
      and nurses take pride in meeting the needs of patients and families.

PMID- 12518834
TI  - A perioperative nurse liaison program: CNS interventions for cancer patients and
      their families.
AB  - Cancer surgery causes stress and anxiety for families and patients. Knowing that
      communication between family and health care professionals is traditionally
      fragmented during the perioperative period, Memorial Sloan-Kettering Cancer
      Center developed a family-centered program to improve information exchange. This
      article describes the Perioperative Clinical Nurse Specialist program and the
      process by which ongoing communication of clinical information and psychosocial
      support for waiting relatives occurs. Good communication during the preoperative,
      intraoperative, and postoperative period is characteristic of quality care at a
      critical time. The subject program serves to bridge the gap in the continuum of
      perioperative care.

PMID- 12518835
TI  - Complementary approaches to palliative oncological care.
AB  - The popularity of complementary and alternative medicine (CAM) has increased
      tremendously in recent years. Thus, it is imperative to distinguish between
      alternative therapies that can be dangerous and complementary therapies that are
      primarily palliative and augment conventional treatment. Memorial Sloan-Kettering
      Cancer Center's Integrative Medicine Service offers complementary therapies to
      patients in an attempt to improve quality of life and provide symptom management.
      In addition to clinical services, it also provides education to health care
      professionals and the public and performs clinical and laboratory research on
      complementary modalities and the antitumor properties of botanicals. If CAM is to
      be accepted by mainstream medicine, research must be done usingstandard research
      methodologies.

PMID- 12518837
TI  - The development of a benchmarking system for a cancer patient population.
AB  - Benchmarking, while a useful way to compare outcomes among health care
      institutions, has been less useful for institutions dealing with specialty
      patient populations such as cancer, rehabilitation, or psychiatry. Because of
      regulatory requirements mandating the use of benchmarking for accreditation and
      performance improvement purposes, a group of comprehensive cancer centers
      developed a specialized database for benchmarking outcomes for cancer patients.
      This article describes the development of the database and some of the obstacles
      encountered by the group. It also outlines solutions to the obstacles. Key words:
      benchmarking, cancer, quality

PMID- 12518836
TI  - Improving patient meal satisfaction with room service meal delivery.
AB  - Cancer and cancer therapies cause side effects that prevent patients from
      consuming adequate amounts of food. As evidenced by patient meal consumption
      studies conducted at patients' bedside, only 39 percent of patients surveyed
      consumed greater than 50 percent of their main entree. The Food and Nutrition
      Services Department at Memorial Sloan-Kettering Cancer Center used the
      organization's performance improvement process, STRAIGHT-A, to develop and
      execute a room service program designed to increase patient meal consumption and
      improve patient meal satisfaction A multidisciplinary task force developed
      policies and procedures and tested new menu items as part of the room service
      plan. After program implementation, 88 percent of patients surveyed consumed
      greater than 50 percent of their main entree.

PMID- 12518838
TI  - Patients' satisfaction and importance ratings of quality in an outpatient
      oncology center.
AB  - Oncology patients requiring outpatient services have expectations that must be
      addressed to ensure continuous and improved quality of care. A convenience sample
      of 96 patients recruited from an oncology outpatient center completed a 26-item
      patient satisfaction questionnaire (SEQUS). Overall satisfaction ratings indicate
      that patients are satisfied with their care. Patients' perception of waiting time
      and lack of questioning regarding their medications by the pharmacist were
      identified as two areas needing improvement. Findings suggest that by identifying
      what is most important to patients, nurses can readily modify the care
      environment to enhance patient satisfaction and quality of care.

PMID- 12518839
TI  - Improving the blood product ordering to administration process.
AB  - A four-pronged approach to improving the blood product delivery system resulted
      in a significant decrease in the number of blood products ordered STAT, increased
      ability of the blood bank to fulfill STAT requests in a timely manner, and a
      significant decrease in the number of blood products outdated and discarded.
      KEYWORDS: blood products, performance improvement

PMID- 12518840
TI  - An interdisciplinary approach to the provision of patient support resources
      across the oncology care continuum: description of a performance improvement
      project.
AB  - Cancer survival has improved, and more attention is now being focused on quality
      of life. Quality-of-life issues include the physical, psychological, social,
      spiritual, and financial aspects of caring. Because patient support services can
      play an important role in helping patients cope with their disease, they are
      critical to patients with cancer and their families. This article describes the
      methods used to address the need for patient support resources and identifies the
      process for identifying and evaluating existing resources and developing
      additional ones. The project goal was to streamline patient care access across
      the oncology care continuum from prevention, diagnosis, and treatment to end of
      life in ambulatory, hospital, and hospice settings.

PMID- 12518841
TI  - Patient identification: the foundation for a culture of patient safety.
AB  - Patients, consumer advocacy groups, and regulatory and accrediting bodies have
      spoken out about the importance of patient safety in the health care environment.
      Understandably, patient safety is a leading concern for both consumers and health
      care providers. These efforts have encouraged health care organizations and
      providers to review and revise, as necessary, routine practices that contribute
      to a culture of patient safety and avoid medical errors. This article outlines
      the process and outcome of a performance improvement initiative to develop a
      standard patient identification policy.

PMID- 12518842
TI  - Establishing clinical guidelines for the management of acute hypersensitivity
      reactions secondary to the administration of chemotherapy/biologic therapy.
AB  - A performance improvement initiative was undertaken to establish treatment
      guidelines for the management of infusion-related hypersensitivity reactions
      (iHSRs) secondary to the administration of chemotherapy/biologic therapy and to
      develop an efficient process to ensure application of these standards in the care
      of patients at increased risk of experiencing iHSRs. The project yielded a
      standardized approach that ensures the application of an evidence-based standard
      of care in managing these reactions. In addition, the effort resulted in
      improvements in the reporting of this type of adverse drug reaction (ADR) to the
      institutional ADR reporting program.

PMID- 12518843
TI  - Malaria infections are randomly distributed in diverse holoendemic areas of Papua
      New Guinea.
AB  - Malaria is holoendemic in the lowlands of Papua New Guinea (PNG), and
      interactions among Plasmodium species may influence prevalence of mixed
      infections. Previously, field samples from a cross-sectional survey in Dreikikir,
      East Sepik Province, analyzed by blood smear and polymerase chain reaction (PCR),
      showed that mixed infections were common and randomly distributed in this malaria
      endemic region. To evaluate further whether Plasmodium species distribution is
      random, blood smear- and PCR/sequence-specific oligonucleotide probe
      hybridization-based analyses of cross-sectional survey samples were conducted in
      2 additional malaria holoendemic regions of northern PNG. Despite ecologic,
      species prevalence, and transmission season differences in these new surveys, all
      4 Plasmodium species were found to be randomly distributed in each area; random
      distribution patterns also were observed when study populations were divided into
      age groups. These findings provide consistent evidence that Plasmodium species
      infections occur independently of one another in PNG malaria holoendemic sites.
      This independent occurrence suggests that age-dependent, acquired malaria
      immunity has limited influence on the distribution pattern of Plasmodium species
      infections in endemic human populations; infection by 1 human malaria parasite
      species does not reduce susceptibility to infection by others; and malaria
      vaccines would exhibit limited protection against blood-stage infection by
      heterologous Plasmodium species.

PMID- 12518844
TI  - Short report: Failure of the OptiMAL rapid malaria test as a tool for the
      detection of asymptomatic malaria in an area of Thailand endemic for Plasmodium
      falciparum and P. vivax.
AB  - We evaluated the efficacy of the OptiMAL assay in a cross-sectional malaria
      survey in western Thailand from April to August 2001. Expert microscopy of Giemsa
      stained thick and thin blood films was used as the gold standard. Positive
      control lines were evident in 99% (1,128 of 1,137) of the assays tested. However,
      34% (384 of 1,128) of assays produced an aberrant result (a positive P.
      falciparum-specific line and a negative panmalarial line). False-positive
      panmalarial and Plasmodium falciparum-specific lines occurred in 25.9% (270 of
      1,042) and 60.3% (628 of 1,042) of microscopy-negative samples, respectively. Due
      to the preponderance of false-positive test results, it was necessary to develop
      subjective criteria for test positivity based on line intensity. For
      determination of assay performance during this study, we therefore considered all
      test lines that were scored as intermediate or strong as positive and lines that
      were faint as negative. Using these criteria, we determined that the sensitivity
      of the OptiMAL assay for P. falciparum was 25% with > 500 parasites/microl and
      10.5% with > 100 parasites/microl, while for P. vivax, the sensitivity at the
      same parasite rates was 100% and 41.7%, respectively. Further studies are
      required to determine whether the problems we identified are limited to this
      particular lot of OptiMAL assays.

PMID- 12518845
TI  - Prevalence of Plasmodium falciparum infection in pregnant Cameroonian women.
AB  - Between 1995 and 1998, a longitudinal study was conducted at 2 health centers in
      Cameroon to determine the prevalence of Plasmodium falciparum infection in
      pregnant women. There were 520 pregnant women enrolled at a rural clinic in the
      village of Etoa and 199 enrolled at the Biyem Assi Clinic in the city of Yaounde.
      In Etoa, pregnant women were younger, fewer took prophylaxis, and malaria
      prevalence was higher compared with pregnant women in the Biyem Assi Clinic. The
      prevalence of malaria infection peaked during the fourth month of pregnancy at
      both sites. Age was identified as a major risk factor because women < or = 20
      years old were 1.8 and 3.4 times more likely to have malaria infection than women
      > 20 years old at Etoa and the Biyem Assi Clinic after adjusting for gravidae and
      other factors. The use of chemoprophylaxis and seasonality did not have a major
      effect.

PMID- 12518846
TI  - A biologic basis for integrated malaria control.
AB  - In a series of models of Plasmodium falciparum dynamics, spontaneous local
      extinctions of the parasite sometimes occurred under steady, perennial
      transmission conditions. These extinctions occurred only with extremely low
      mosquito densities or when the parameter describing the duration of human
      infection-blocking immunity was at its maximum value, and, simultaneously, those
      describing vector survivorship and the duration of human infectivity were at
      their minimum values. The range and frequency of extinctions increased with
      seasonal transmission, and decreased with the emergence of recombinant genotypes.
      Here we extend the immunity parameter up to levels that would describe a
      successful vaccine, and examine the combined influences of seasonality, genotype
      cross-reactivity, meiotic recombination, and human population turnover on
      parasite persistence. As Ross did 90 years ago, we conclude that malaria control
      programs that encompass several methods and targets of intervention are the most
      likely to succeed. Success is more likely if programs are cognizant of local
      circumstances of transmission, and, within that context, aim to reduce vector
      survivorship and human infectivity as well as augment human immunity.

PMID- 12518847
TI  - Gambian children successfully treated with chloroquine can harbor and transmit
      Plasmodium falciparum gametocytes carrying resistance genes.
AB  - Polymorphisms in two genes of Plasmodium falciparum (P. falciparum multidrug
      resistance 1 [pfmdr1] and P. falciparum chloroquine [CQ] resistance transporter
      [pfcrt]) are associated with CQ treatment failure. We found significant linkage
      disequilibrium between these loci among isolates from symptomatic Gambian
      children (P = 0.026) and strong selection for the resistance-associated alleles
      pfmdr1-86Tyr and pfcrt-76Thr in children with persistent or re-emerging P.
      falciparum trophozoites during post-treatment follow-up (P = 1.9 x 10(-7)).
      Therefore, this genotype is characteristic of resistant infections among our
      study population. Since the long-term public health impact of parasites carrying
      such resistant genotypes depends upon their transmissibility, we examined the
      prevalence of pfmdr1-86Tyr and pfcrt-76Thr among Gambian children harboring
      sexual stage parasites during post-treatment follow-up. Gametocytes that emerged
      after successful treatment with CQ were significantly more likely to be of this
      genotype than were those emerging after other treatments (P = 4.83 x 10(-4)), and
      were infective to Anopheles mosquitoes. Therapeutic success may thus be
      accompanied by public health failure as cured children pass resistance genes on
      to mosquitoes at an enhanced rate.

PMID- 12518848
TI  - Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium
      knowlesi infections.
AB  - Experimental infection of non-human primates with simian malaria parasites offers
      a controlled system to study malarial immunity. Plasmodium cynomolgi (P. vivax
      like) and P. knowlesi (P. falciparum-like) infections in the rhesus monkey were
      used as a model to test the hypothesis that initial acute infection stimulates
      type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti
      inflammatory response upon re-infection. This study analyzed cytokine gene
      expression (interleukin-12, interferon-gamma, tumor necrosis factor-alpha = type
      1; interleukin-4, interleukin-10 = type 2) using a semi-quantitative reverse
      transcriptase-polymerase chain reaction in monkeys infected with each of the
      parasites (three per group). Clinicoparasitologic and serologic parameters were
      also monitored. Monkeys were re-infected to assess whether enhanced immunity
      could increase parasite clearance. The immune response to P. cynomolgi infection
      in rhesus monkeys seemed to be mediated by anti-parasite, pro-inflammatory
      responses during primary infection with a transition to protective type 2
      responses after repeat infection. The immune responses to P. knowlesi infection
      were more varied. Anti-inflammatory responses were more prevalent during primary
      infection. Repeat infection stimulated a wide variety of responses; most included
      expression of tumor necrosis factor-alpha, a cytokine that has been associated
      with inflammatory and host-destructive effects (weight loss, fever, anemia).
      These observations further confirmed that the simian malaria/rhesus monkey model
      is well suited for studies on the regulation of immunity to acute Plasmodium
      infection.

PMID- 12518849
TI  - Low antibody responses to variant surface antigens of Plasmodium falciparum are
      associated with severe malaria and increased susceptibility to malaria attacks in
      Gabonese children.
AB  - We measured the levels of IgG antibodies with specificity for the variant surface
      antigens (VSA) of Plasmodium falciparum in plasma samples from a cohort of
      Gabonese children participating in a longitudinal case-control malaria study.
      Children with mild malaria had significantly higher anti-VSA IgG responses than
      their matched counterparts with severe malaria, most markedly during
      convalescence and when they were healthy. Over the course of the study, almost
      twice as many children who presented initially with mild rather than severe
      malaria developed antibodies recognizing the VSA expressed by each of a panel of
      three isolates, and those with the highest anti-VSA IgG responses had the lowest
      malaria attack rates. The results suggest that the clinical outcome of P.
      falciparum infection in young African children depends on their ability to both
      develop and maintain a broad profile of anti-VSA IgG antibodies, and that this
      ability is diminished in children who have experienced a severe malaria attack.

PMID- 12518850
TI  - Impact of preseason treatment on incidence of falciparum malaria and parasite
      density at a site for testing malaria vaccines in Bandiagara, Mali.
AB  - Treating malaria before immunizing has been standard in malaria vaccine field
      trials. To assess the impact of this practice on subsequent infection and disease
      incidence, we conducted a randomized cohort study in Bandiagara, Mali. Subjects
      received a treatment dose of sulfadoxine-pyrimethamine (SP) or no treatment at
      the beginning of the transmission season. Cumulative and age-specific incidence
      of clinical episodes was similar between the 2 groups, but SP treatment delayed
      the median time to first clinical episode from 38.5 to 68 days, and after this
      initial period of protection, disease incidence in the SP group quickly surpassed
      the incidence in the untreated group. Parasite densities during disease episodes
      were lower in the SP group. SP was chosen as the drug for initial parasite
      clearance for the following reasons: 1) it has been used in previous vaccine
      trials; 2) our studies have found it to have >99% efficacy in treating
      uncomplicated malaria in Mali compared to 85-90% efficacy for chloroquine in this
      area; 3) SP is the approved second-line antimalarial agent in Mali; and 4) its
      single-dose regimen ensures compliance when treatment is directly observed.

PMID- 12518851
TI  - Genetic diversity of Plasmodium falciparum field samples from an isolated
      Colombian village.
AB  - Colombian field isolates of Plasmodium falciparum were analyzed for genetic
      diversity. Fifty-three samples were collected as thick smears from patients
      living in Pangui, an isolated area with low migration. While the samples were
      being collected, Pangui was experiencing an epidemic outbreak of malaria. The
      samples were typified using nested polymerase chain reaction (PCR) amplification
      of block 2 of the merozoite surface protein 1 (MSP1) gene and nested PCR with
      mutation-specific primers for position 108 of the dihydrofolate reductase enzyme
      gene. The results for the circulating population of parasites in Pangui show low
      diversity--four allelic forms--using MSP1 as a marker, a fact that contrasts with
      data reported for certain Asian and African zones. A high percentage of mixed
      infections was observed, as was high complexity of the infection. No differential
      distributions were found for any allelic type.

PMID- 12518852
TI  - The role of agricultural use of insecticides in resistance to pyrethroids in
      Anopheles gambiae s.l. in Burkina Faso.
AB  - Agricultural use of insecticides is involved in the selection of resistance to
      these compounds in field populations of mosquitoes in Burkina Faso. Anopheles
      gambiae s.l. was resistant to permethrin and DDT in cotton-growing and urban
      areas, but susceptible in areas with limited insecticide selection pressure (rice
      fields and control areas). Nevertheless, resistance to these insecticides was
      observed in a village on the outskirts of the rice fields at the end of the rainy
      season, suggesting that the latter population of mosquitoes had migrated from the
      surrounding cotton villages into the rice fields. A seasonal variation of
      resistance observed in the cotton-growing area is related to the distribution of
      the molecular M and S forms of An. gambiae, since resistance to pyrethroids has
      so far only been reported in the S form. Pyrethroid resistance in west African
      An. gambiae was conferred by target site insensitivity through a knockdown
      resistance (kdr)-like mutation, which was present at high frequencies in
      mosquitoes in the cotton-growing and urban areas.

PMID- 12518853
TI  - Outbreak of amebiasis in Tbilisi, Republic of Georgia, 1998.
AB  - In 1998, we investigated a suspected outbreak of amebic liver abscesses caused by
      Entamoeba histolytica in the Republic of Georgia, using a case-control study. A
      questionnaire was administered and blood samples were obtained from cases and
      controls for serologic diagnosis. Medical records showed that E. histolytica
      infections were rarely diagnosed before 1998. However, from July through
      September 1998, 177 cases of suspected amebiasis were identified. Of 52 persons
      who had diagnosed liver abscesses, 37 (71%) were confirmed serologically to have
      antibodies against E. histolytica, compared with 11 of 53 persons (20.8%)
      diagnosed with intestinal amebiasis. In addition, 9-14% of asymptomatic controls
      were seropositive. Logistic regression identified the fact that interruptions in
      the water supply, decreases in water pressure, and increased water consumption
      were significantly associated with infection. The data support the hypothesis
      that drinking water was the source of infection, either because of inadequate
      municipal water treatment or contamination of municipal water in the distribution
      system.

PMID- 12518854
TI  - Defective production of reactive oxygen intermediates (ROI) in a patient with
      recurrent amebic liver abscess.
AB  - Previously, we reported the case of a man in the fourth decade of life afflicted
      with three independent episodes of amebic liver abscesses over a period of 4
      years. Previous evidence has indicated that the cellular immune response is
      involved in protection against recurrent invasive amebic infection, and
      macrophage-mediated effector mechanisms appear important for host resistance to
      Entamoeba histolytica infection. The aim of the present work was to investigate
      locomotor activity and oxidative burst function of peripheral mononuclear cells
      of this individual after healing of the third amebic liver abscess. A locomotion
      assay using Boyden chemotaxis chambers and the respiratory burst evaluated by
      chemiluminescence were performed in both mononuclear phagocytes (MPs) and
      polymorphonuclear (PMN) leukocytes. Levels of salivary IgA and serum IgG anti
      amebic antibodies were followed during 48 months after the second amebic liver
      abscess. Results obtained showed a deficiency in MP but not in PMN leukocyte
      respiratory burst. Respiratory burst is a major microbicidal mechanism in MP
      leukocytes; this also has been considered as a host resistance strategy against
      E. histolytica. It may be at least one risk factor in our patient that was
      responsible for recurrence of amebic liver abscess.

PMID- 12518855
TI  - Calreticulin-like molecule in trophozoites of Entamoeba histolytica HM1:IMSS
      (Swissprot: accession P83003).
AB  - In this work, we report the partial sequence of a 51 kDa protein of Entamoeba
      histolytica that is highly immunogenic in humans. Partial sequencing of the N
      terminal end showed that 18 of the first 20 amino acid residues of the protein
      were identified uniquely, indicating that the final product was a homogeneous
      protein preparation. The N-terminal sequence that was found was:
      KVYFEETFENGWKXIWSKW. Comparing the 19-amino acid sequence of the protein in
      automated databases shows significant similarity with amino acid sequences of the
      calreticulin-like protein of spinach leaves (77%) and of the calreticulin
      precursor of Dictyostelium discoideum (60%).

PMID- 12518856
TI  - Influence of vertebrate blood meals on the development of Leishmania (Viannia)
      braziliensis and Leishmania (Leishmania) amazonensis in the sand fly Lutzomyia
      migonei (Diptera: Psychodidae).
AB  - The effect of blood meals from humans and seven domestic, wild, or laboratory
      animals (dogs, horses, chickens, rats, opossums, mice, and hamsters) on the
      development of Leishmania braziliensis and L. amazonensis was studied in the sand
      fly Lutzomyia migonei. The development of L. braziliensis and L. amazonensis
      exhibited peripylarian and suprapylarian patterns of development, respectively,
      in the sand fly gut with all blood meals tested. The blood meal sources
      influenced the infection rate of the sand flies. In both the Leishmania species,
      the highest parasite density was obtained with blood from wild rats followed by
      skunk, human, and horse. The epidemiological significance of these observations
      may be related to the distribution of leishmaniasis and needs to be evaluated
      further.

PMID- 12518857
TI  - Climatic and demographic determinants of American visceral leishmaniasis in
      northeastern Brazil using remote sensing technology for environmental
      categorization of rain and region influences on leishmaniasis.
AB  - Remote sensing (RS) permits evaluation of spatial and temporal variables that can
      be used for vector-borne disease models. A Landsat Thematic Mapper scene covering
      Caninde, Ceara in northeastern Brazil (September 25, 1986) was spectrally
      enhanced and classified using ERDAS (Atlanta, GA) Imagine for 873 4-km2 areas.
      The population and number of cases of American visceral leishmaniasis (AVL) were
      determined for each 4-km2 area. Relative risk (RR) ratios were calculated for
      climate, demographic, and case data recorded for 17 years by the Municipality of
      Conide. The RR of AVL for a child less than 10 years old from the foothills
      relative to non-foothill residency was 4.0 (95% confidence limit = 3.5, 4.5). The
      RR of AVL in children was 9.1 during a time when the three-year rolling rain
      average (current year plus two previous year's precipitation) was between 40 and
      60 cm relative to rain greater than 100 cm. The results suggest that features
      detected by RS techniques combined with climatic variables can be used to
      determine the risk of AVL in northeastern Brazil.

PMID- 12518858
TI  - Detection and stability of Japanese encephalitis virus RNA and virus viability in
      dead infected mosquitoes under different storage conditions.
AB  - A semi-nested polymerase chain reaction (PCR) was evaluated for detection of
      Japanese encephalitis (JE) virus in infected mosquitoes stored under simulated
      northern Australian summer conditions. The effect of silica gel, thymol, and a
      combination of the two on RNA stability and virus viability in dead mosquitoes
      were also examined. While JE virus RNA was relatively stable in mosquitoes held
      for up to 14 days after death, viable virus was not detected after day 1. Thymol
      vapor inhibited fungal contamination. Detection of single mosquitoes infected
      with JE virus in large pools of mosquitoes was also investigated. Single
      laboratory-infected mosquitoes were detected in pools of < or = 200 mosquitoes
      and in pools diluted to 0.2/100 and 0.1/100 mosquitoes, using the semi-nested
      PCR. However, the ability to detect live virus decreased as pool size increased.
      The semi-nested PCR proved more expensive than virus isolation for pools of 100
      mosquitoes. However, the semi-nested PCR was faster and more economical using
      larger pools. Results indicate that surveillance of JE virus in mosquitoes using
      the semi-nested PCR is an alternative to monitoring seroconversions in sentinel
      pigs.

PMID- 12518859
TI  - Epidemic of hepatitis E in a military unit in Abbotrabad, Pakistan.
AB  - An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad,
      Pakistan was traced to fecal contamination of a water system. Of 109 men
      hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis
      E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E
      (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a
      subset of 44 men with acute hepatitis E from whom three serum specimens were
      obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs)
      decreased from 1,519 during the outbreak to 657 at four months. The IgM anti-HEV
      was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute
      disease), but in only six (14%) four months later. The prevalence of anti-HEV in
      this population before the outbreak was estimated to be 30%. The presence of IgG
      anti-HEV appeared to protect against clinical hepatitis or development of
      serologic evidence of new infection with HEV. This is the second major epidemic
      of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked
      immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by
      this ELISA protects against disease is important for assessment of vaccine
      development.

PMID- 12518860
TI  - Transmission intensity and the patterns of Onchocerca volvulus infection in human
      communities.
AB  - We focus on possible constraints upon Onchocerca volvulus establishment in humans
      in relation to exposure rates to infective larvae (L3) as measured by the annual
      transmission potential (ATP). We use mathematical and statistical modeling of pre
      control west African (savanna), Mexican, and Guatemalan data to explore two
      hypotheses relating human infection to transmission intensity: microfilarial (mf)
      loads either saturate with increasing ATP or become (asymptotically) proportional
      to the ATP. The estimated proportion of L3 developing into adult worms ranged
      from 7% to 0.3% (low and high intensity areas, respectively). Relationships
      between mf prevalence and both mf and transmission intensity were nonlinear and
      statistically similar between west Africa (Simulium damnosum s.l.) and Meso
      America (S. ochraceum s.l.). This similarity extended to the relationship between
      mf intensity and ATP. The critical biting rates for onchocerciasis introduction
      and persistence (which depended on vector competence and host preference), were
      approximately 10-fold higher in settings where onchocerciasis is transmitted by
      S. ochraceum than in those where the vector is S. damnosum. A role for focal
      vector control in Mexico and Guatemala, in addition to nodulectomy and
      ivermectin, is suggested.

PMID- 12518861
TI  - Intraobserver and interobserver variation of ultrasound diagnosis of
      Oesophagostomum bifurcum colon lesions.
AB  - Infection by the nematode Oesophagostomum bifurcum is focally distributed in
      Africa and causes a syndrome of abdominal pain, obstruction, or abdominal mass
      because of its predilection for invasion of colonic mucosa. To determine the
      reliability of ultrasound for the detection of colon pathology induced by this
      parasite, three studies to assess the intraobserver and interobserver variation
      of the technique were performed. In an area of northern Ghana endemic for O.
      bifurcum, 181 people from a low-prevalence village and 62 people from a high
      prevalence village were examined twice by the same observer, and 111 people were
      independently examined by two observers in a moderately endemic village. The
      kappa statistics for the prevalence observations in the three studies were 0.82,
      0.87, and 0.81, respectively, and kappa values for the intensity observations
      were 0.66, 0.63, and 0.71, respectively. The upper 95% confidence intervals of
      the average absolute difference in nodule size measurements in Study 1 and Study
      3 were 3.6 and 4.5 mm, respectively. Therefore, ultrasound is useful in the
      diagnosis and management of O. bifurcum colon infection.

PMID- 12518863
TI  - Simultaneous detection of the tumor suppressor FHIT gene and protein using the
      multi-functional biochip.
AB  - The tumor suppressor gene, fragile histidine triad (FHIT), encompasses the most
      common human chromosomal fragile site, at 3pl4.2. Detection of FHIT gene is
      important in cancer diagnostics since its alterations have been associated with
      several human cancers. A unique multi-functional biochip for simultaneous
      detection of FHIT DNA and FHIT protein on the same platform was applied. The
      design of the biochip is based on miniaturization of photodiodes, where
      functioning of multiple optical sensing elements, amplifiers, discriminators, and
      logic circuitry are integrated on a single IC board. Performance of biochip is
      based on biomolecular recognition processes using both DNA and protein
      bioreceptors, Cy5-labeled probes and laser excitation. Application of biochip for
      concurrent detection of various immobilized target DNA and protein molecules and
      multiplex of DNA and protein on the same microarray was accomplished. Linearity
      of biochip for quantitative measurements was demonstrated. Results demonstrated
      utility of this multi-functional biochip as a useful detection technology with
      applications in biological and clinical laboratories.

PMID- 12518862
TI  - The serum resistance-associated gene as a diagnostic tool for the detection of
      Trypanosoma brucei rhodesiense.
AB  - In the search for new diagnostic methods that would distinguish Trypanosoma
      brucei rhodesiense from T. b. brucei and T. b. gambiense, we have developed two
      polymerase chain reaction (PCR) primer sets. The first primer set was derived
      from the serum resistance-associated (SRA) gene of T. b. rhodesiense that confers
      resistance to lysis by normal human serum (NHS). The specificity of the SRA-based
      PCR was tested on 97 different trypanosome populations originating from various
      taxonomic groups, host species, and geographic regions. Only one of 25 T. b.
      rhodesiense samples was negative in this PCR, and none of 72 other samples were
      positive in this assay. Interestingly, a reference T. brucei strain (TREU927/4)
      currently used for genome sequencing was negative for the SRA gene; however, this
      strain was resistant to lysis by NHS. The second primer set was derived from a
      specific variant surface glycoprotein (VSG) expression site where the SRA gene is
      expressed (R-ES). This primer set identified the strain as T. b. rhodesiense in
      17 of 17 SRA gene-positive strains in which it was tested. These data strongly
      suggest that expression of the SRA gene is generally involved in resistance to
      lysis by NHS in T. b. rhodesiense strains.

PMID- 12518864
TI  - Loss of heterozygosity at loci of candidate tumor suppressor genes in
      microdissected primary non-small cell lung cancer.
AB  - To investigate the etiological association of allelic loss at chromosomal regions
      containing tumor suppressor genes (TSGs) in non-small cell lung cancer (NSCLC) in
      Taiwan, we examined 48 microdissected NSCLC samples for loss of heterozygosity
      (LOH) at nine loci where TSGs are localized nearby. The associations of LOH at
      each locus with clinicoparameters and prognosis were also examined. The frequent
      LOH was observed using markers, D3S1285 near the FHIT gene (58.3%), D17S938 near
      the p53 gene (56.7%), D9S925 near the p16 gene (54.5%), and D13S153 near the RB
      gene (47.6%). The occurrence of LOH at each TSG locus was compared with the
      patients' clinicoparameters. The incidence of LOH at D17S938 (p53 gene) and
      D3S4545 (VHL gene) was significantly higher in squamous carcinoma tumors than in
      adenocarcinoma tumors (P = 0.003 and 0.024, respectively). LOH of these two loci
      also occurred frequently in tumors from smoker patients compared to that from
      nonsmoker patients (P = 0.013 and 0.025, respectively). LOH at D13S153 (RB gene)
      was also associated with smoking (P = 0.008). In addition, the prognostic
      analyses indicated that the patients with LOH at D18S535 (18q21, near the SMAD2/4
      gene) had significantly longer post-operative survival time compared to those
      without LOH (P = 0.03). Our results suggested that LOH at FHIT, p53, and p16
      genes may occur frequently in NSCLC patients in Taiwan. In addition, LOH at p53,
      RB, and VHL may associate with smoking or squamous carcinoma patients and LOH at
      SMAD2/4 may be correlated with better prognosis.

PMID- 12518865
TI  - Evidence-based policy recommendations on cancer screening and prevention.
AB  - Ideally, practice guidelines for cancer prevention should reflect the available
      empirical evidence. Although the most persuasive arguments for the efficacy of an
      intervention come from randomized controlled trials (RCTs), such studies are not
      always feasible because of ethical or logistical reasons. The advent of evidence
      based medicine has underscored the need for consortia of researchers specialized
      in reviewing the biomedical literature on a systematic basis, ranking studies
      according to their design, quality, and generalizability of results. This review
      summarizes the recommendations and policies on screening and prevention of
      specific types of cancers from North American and international organizations
      such as: the National Cancer Institute's Physicians's Data Query Program, the US
      Preventive Services Task Force, the Canadian Task Force on the Preventive Health
      Care Force, and the Cochrane Collaboration.

PMID- 12518866
TI  - Early detection of cancer: knowledge and behavior among Dutch adults.
AB  - This paper reports on knowledge and behavior among Dutch adults (n = 1530)
      regarding early detection of cancer (passive detection, active detection and help
      seeking behavior). Written questionnaires assessed knowledge of detection methods
      and cancer symptoms, symptom recognition, detection behaviors, and help-seeking
      behaviors. Respondents did not have much general knowledge of detection methods
      and cancer symptoms, but recognized most cancer symptoms. More women than men
      paid attention to cancer symptoms. For most symptoms, medical help would be
      sought within the appropriate time by the majority of the respondents. Principal
      component analyses revealed relations between symptoms pertaining to the
      'interior' body and those pertaining to the 'exterior' body. Correlations between
      symptom recognition, detection behavior and help-seeking behavior were low.
      Differences in demographic groups and differences in knowledge and behavior
      require adaptation of future health education on early detection of cancer to
      different groups.

PMID- 12518867
TI  - A proposed mechanism of tamoxifen in breast cancer prevention.
AB  - Recent clinical trials suggest that tamoxifen (TAM) is a preventive agent for
      breast cancer, however, the mechanism is unknown. Previously, we found that both
      17beta-estradiol (E2) and estrone (E1) could be activated by epoxidation
      resulting in their ability to bind to DNA, forming DNA adducts both in vitro and
      in vivo, and to inhibit nuclear DNA-dependent RNA synthesis. Since epoxidation is
      required for the activation of many well-known chemical carcinogens including
      benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, aflatoxins, etc., we proposed
      that estrogen epoxidation is the underlying mechanism for the initiation of
      breast cancer (Carcinogenesis 17 (1996) 1957). Here, we report that TAM is able
      to dramatically inhibit the formation of E2 and E1 epoxides as measured by both
      the loss of their ability to inhibit nuclear DNA-dependent RNA synthesis and to
      bind to nuclear DNA. These findings suggest that the breast cancer preventive
      effect of TAM may be through a competitive epoxidation inhibition mechanism that
      prevents the formation of E2 and E1 epoxides and consequently, the initiation of
      breast cancer.

PMID- 12518868
TI  - Glutathione S-transferase GSTP1 genotypes are associated with response to
      androgen ablation therapy in advanced prostate cancer.
AB  - We determined whether the glutathione S-transferase GSTP1 Ile105 --> Val105
      substitution is associated with response to androgen ablation therapy in patients
      with advanced prostate cancer. As response may be associated with tumor grade,
      Gleason score, clinical T stage and presence of metastases we also determined if
      GSTP1 genotypes were associated with these prognostic parameters. We speculated
      that GSTP1 Ile105/Ile105 would be linked with good response to androgen ablation
      therapy and, low/moderate tumor grade, 1/2 clinical T-stage, Gleason score < 6
      and, no metastases. Genotype frequencies in cases and controls were not
      significantly different (P = 0.70) indicating that allelism in GSTP1 is not
      associated with susceptibility. There was no association between GSTP1
      (Ile105/Ile105 versus Ile105/Val105 and Val105/Val105) and grade (P = 0.28, OR =
      0.92), Gleason score (P = 0.84, OR = 0.94) or metastatic state (P = 0.68, OR =
      0.88) though the frequency of GSTP1 Ile105/Ile105 was higher in cases with stage
      1/2 tumors than those with stage 3/4 tumors (P = 0.03, OR = 1.89). GSTP1
      Val105/Val105 was also associated with response to hormone ablation therapy.
      Thus, the GSTP1 Ile105/Ile105 frequency was significantly higher in 86/118
      patients who demonstrated a good response than in those with poor response (P =
      0.03, OR = 2.70). We speculate that the association of GSTP1 with response
      results from an effect of the gene product early in carcinogenesis.

PMID- 12518870
TI  - Evaluation of a "loss-framed" minimal intervention to increase mammography
      utilization among medically un- and under-insured women.
AB  - This study was conducted because mammography is under-utilized, even though it is
      the most effective early detection screening device for breast cancer. A loss
      framed telephonic message based on prospect theory was evaluated for the effects
      on mammography utilization among medically un- and under-insured women living in
      demographically similar rural counties in Florida. The sample consisted mostly of
      White women (approximately 89%) 50-64 years old. Experimental group participants
      received the loss-framed message telephonically and those in the comparison group
      received the "usual telephone procedure." Logistic regression analyses revealed
      that women who received the loss-framed message were six times more likely to
      obtain a mammogram (OR = 6.6, P < 0.0001). The impact of the loss-framed message
      persisted even after adjustment for initial versus re-screen mammogram effects.
      This in-reach, loss-framed, minimal intervention seems to have viability and may
      serve as an alternative or adjunct program for encouraging women to receive
      mammograms.

PMID- 12518869
TI  - Dietary factors affecting uterine weights of immature CD-1 mice used in
      uterotrophic bioassays.
AB  - A study was conducted to determine the effects of dietary factors in natural
      ingredient and purified diets on uterine weights of immature CD-1 mice used in
      uterotrophic bioassays. Factors evaluated included body weight gain, dietary
      phytoestrogen content, total metabolizable energy, and percent crude fiber.
      Fifteen to 147 mice per group, housed 5 per cage, were randomly assigned to each
      of the 20 test diets. The test diets were fed for 7 days to 15-day old immature
      female CD-1 mice and their body weight gain and uterine weights were determined.
      Analysis of covariance procedures were used to evaluate differences in uterine
      weights, after adjusting for body weight and time-related trends. Fisher's least
      significant difference test was used to compare adjusted uterine weights and
      weight gains among the test diets. Additionally, multiple linear regression
      procedures were used to identify those characteristics of the rodent diet that
      were most predictive of the adjusted uterine weights. Total metabolizable energy
      was significantly (P < 0.01) correlated with and was predictive of uterine
      weights. The following dietary variables were not significantly predictive of
      uterine weights: total daidzein and genistein content, percent protein, fat, N-FE
      (carbohydrates) or percent crude fiber. We concluded that: (1) total
      metabolizable energy (ME) in natural ingredient or purified diets has a
      significant (P < 0.01) effect on the uterine weights of immature mice used in 7
      day uterotrophic bioassays; (2) a standardized, estrogen-free diet with a
      constant level of ME should be used for conducting uterotrophic assays when
      comparing results between different laboratories or when determining the
      estrogenic or anti-estrogenic activity of endocrine disruptor compounds; (3) the
      mouse uterotrophic assay remains a sensitive bioassay for assessing chemicals for
      estrogenic activity or for the detection of total estrogenic activity in rodent
      diets that may be contaminated with estrogenic compounds, and (4) chemical assays
      should be used to detect or measure low levels of the phytoestrogens in rodent
      diets.

PMID- 12518871
TI  - Corneal sensitivity in dogs with diabetes mellitus.
AB  - OBJECTIVE: To compare aesthesiometer-determined corneal sensitivity between
      diabetic and nondiabetic dogs and to investigate the correlation between corneal
      sensitivity and duration of diabetes or status of glycemic control, as estimated
      by use of glycated blood protein concentrations. ANIMALS: 23 diabetic and 29
      nondiabetic normoglycemic dogs. PROCEDURE: A Cochet-Bonnet aesthesiometer was
      used to measure corneal touch threshold (CTT) in 5 corneal regions of each dog.
      At the time of ocular examination, duration of diabetes mellitus was estimated
      from the history, and blood was drawn for assessment of blood glycosylated
      hemoglobin and serum fructosamine concentrations. RESULTS: Median CTT for
      central, nasal, dorsal, temporal, and ventral corneal regions in nondiabetic dogs
      (1.6, 2.3, 2.8, 2.8, and 5.1 g/mm2, respectively) was significantly lower than in
      diabetic dogs (2.8, 4.0, 5.1, 5.1, and 6.6 g/mm2, respectively). Median regional
      CTT in diabetic dogs was not significantly correlated with estimated duration of
      diabetes mellitus or blood glycated protein concentrations. No significant
      difference was found in regional CTT between eyes of normoglycemic dogs with
      unilateral cataracts. CONCLUSIONS AND CLINICAL RELEVANCE: Diabetic dogs have
      significantly reduced corneal sensitivity in all regions, compared with
      nondiabetic normoglycemic dogs. Regional variation in corneal sensitivity is
      similar in diabetic and normoglycemic dogs. Neither glycemic control nor duration
      of diabetes, as estimated, is significantly correlated with corneal
      hyposensitivity. Corneal nerve dysfunction may be associated with recurrent or
      nonhealing ulcers in diabetic dogs for which no other underlying cause can be
      found.

PMID- 12518872
TI  - Biocompatibility of three-dimensional chondrocyte grafts in large tibial defects
      of rabbits.
AB  - OBJECTIVE: To evaluate biocompatibility and effects of implantation of 3
      dimensional chondrocyte-agarose autografts in tibial defects in rabbits and to
      compare in vitro and in vivo chondrocyte-agarose constructs with respect to cell
      viability, differentiation, and matrix production. ANIMALS: 24 adult New Zealand
      White rabbits. PROCEDURE: Three-dimensional constructs with (grafted group) or
      without (control group) autogenous chondrocytes were implanted into tibial
      defects of rabbits and cultured in vitro. During an 8-week period, defects were
      evaluated radiographically, grossly, histologically, biochemically, and
      immunohistochemically. In vitro constructs were evaluated histologically,
      biochemically, and immunohistochemically. RESULTS: Tibial defects had
      significantly higher radiographic densitometry values at 4 and 6 weeks after
      implantation in grafted group rabbits, compared with control group rabbits.
      Number of observed centers of endochondral ossification was significantly greater
      in defects of grafted group rabbits, compared with control group rabbits. On day
      14, glycosaminoglycan concentration was significantly higher in tibial defects of
      grafted group rabbits, compared to defects of control group rabbits or in vitro
      constructs. At weeks 2, 4, and 8, glycosaminoglycan concentrations were
      significantly lower in the in vitro control constructs, compared with other
      groups. Collagen type I was present in bone and bony callous in defects of
      grafted and control group rabbits. Collagen type II was identified in
      cartilaginous tissues of grafted and control group rabbits. Collagen type X was
      associated with hypertrophic chondrocytes. Only type II collagen was found in the
      in vitro chondrocyte constructs. CONCLUSIONS AND CLINICAL RELEVANCE: Chondrocyte
      agarose grafts are biocompatible in large tibial defects and appear to provide a
      cell source for augmenting endochondral ossification.

PMID- 12518873
TI  - Effects of ventilation and isoflurane end-tidal concentration on intracranial and
      cerebral perfusion pressures in horses.
AB  - OBJECTIVE: To measure the effects of isoflurane end-tidal concentration and mode
      of ventilation (spontaneous vs controlled) on intracranial pressure (ICP) and
      cerebral perfusion pressure (CPP) in horses. ANIMAL: adult horses of various
      breeds. PROCEDURES: Anesthesia was induced and maintained with isoflurane in O2
      in 6 healthy, unmedicated, adult horses. Using a subarachnoid strain gauge
      transducer, ICP was measured. Blood gas tensions and carotid artery pressures
      also were measured. Four isoflurane doses were studied, corresponding to the
      following multiples of the minimum alveolar concentration (MAC): 1.0 MAC, 1.2
      MAC, 1.4 MAC, and 1.6 MAC. Data were collected during controlled ventilation and
      spontaneous ventilation at each dose. RESULTS: increasing isoflurane end-tidal
      concentration induced significant dose-dependent decreases in mean arterial
      pressure (MAP) and CPP but no change in ICR Hypercapnic spontaneous ventilation
      caused significant increases in MAP and ICR compared with normocapnic controlled
      ventilation; no change in CPP was observed. CONCLUSIONS AND CLINICAL RELEVANCE:
      Hypercapnia likely increases cerebral blood flow (CBF) by maintaining CPP in the
      face of presumed cerebral vasodilation in healthy anesthetized horses. The effect
      of isoflurane dose on CBF however, remains unresolved because it depends on the
      opposing influences of a decrease in CCP and cerebral vasodilation.

PMID- 12518874
TI  - Relationship of age, sex, body weight, and hematologic and respiratory variables
      with airway reactivity in adult cats.
AB  - OBJECTIVE: To evaluate the association between airway reactivity and age, sex,
      body weight, and radiographic findings in cats. ANIMALS: 32 mature cats that
      constituted 2 age groups (17 young cats that were 1 to 2 years old and 15 old
      cats that were 12 to 13 years old). PROCEDURE: Cats were placed in the chamber of
      a barometric whole-body plethysmograph (volume, 38 L), and box pressure was
      measured at baseline and after aerosol administration of increasing
      concentrations of carbachol. Airway reactivity was assessed by monitoring
      increases in enhanced pause (PENH), a unitless variable that measures
      bronchoconstriction as derived from dose-response curves. The endpoint chosen was
      the provocative concentration of carbachol that increased PENH to 300% of the
      baseline value (PCPENH300). RESULTS: We did not find a correlation between
      PCPENH300 and sex, body weight, number of eosinophils, PENH before
      bronchoconstriction, respiratory frequency, tidal volume, or minute ventilation.
      Airway reactivity was significantly less in the old cats (mean +/- SD PCPENH300,
      0.578 +/- 0.051%), compared with the value for the young cats (0.053 +/- 0.006%).
      Radiographic patterns differed significantly between groups of cats; a greater
      proportion of old cats (12/15) had bronchointerstitial patterns, compared with
      the proportion of young cats (4/17). CONCLUSIONS AND CLINICAL RELEVANCE: These
      data support the notion that age exerts a strong influence on airway reactivity
      in adult cats, and radiographic differences suggest that structural changes in
      older cats may contribute to this effect. These findings have important
      implications for interpretation of results of airway reactivity tests in cats.

PMID- 12518875
TI  - Serum immunoglobulin E against storage mite allergens in dogs with atopic
      dermatitis.
AB  - OBJECTIVE: To determine the prevalence of serum IgE against the storage mites
      Acarus siro, Blomia tropicalis, and Tyrophagus putrescentiae in a population of
      dogs with atopic dermatitis. SAMPLE POPULATION: Sera from 84 dogs with atopic
      dermatitis residing in various regions of the United States and Europe.
      PROCEDURE: Immunoblotting of sera from atopic dogs was used to identify proteins
      in mite extracts that bound IgE. RESULTS: 94% of the dogs had serum IgE against
      proteins in extracts of 1 or more of the storage mite species. Ninety-five, 92,
      and 89% of the storage mite-sensitive dogs had serum IgE against proteins in
      extracts of A siro, B tropicalis, and T putrescentiae, respectively. Eighty-two
      percent had serum IgE against at least 1 protein in all 3 species. Most of the
      major allergens had molecular weights > 80 kd. A greater percentage of the dog
      sera had IgE against storage mite proteins, compared with proteins of the house
      dust mites Dermatophagoides farinae and D pteronyssinus. CONCLUSION AND CLINICAL
      RELEVANCE: Many dogs with atopic dermatitis have serum IgE against many allergens
      of storage mites. Most of these allergens, like allergens of dust mites, had
      molecular weights > 80 kd. Storage mite sensitivity in dogs may be as important,
      if not more important, than dust mite sensitivity.

PMID- 12518876
TI  - Efficacy of oral supplementation with L-lysine in cats latently infected with
      feline herpesvirus.
AB  - OBJECTIVE: To examine the effects of orally administered L-lysine on clinical
      signs of feline herpesvirus type 1 (FHV-1) infection and ocular shedding of FHV-1
      in latently infected cats. ANIMALS: 14 young adult, FHV-1-naive cats. PROCEDURE:
      Five months after primary conjunctival inoculation with FHV-1, cats were rehoused
      and assigned to receive 400 mg of L-lysine in food once daily for 30 days or food
      only. On day 15, all cats received methylprednisolone to induce viral
      reactivation. Clinical signs of infection were graded, and viral shedding was
      assessed by a polymerase chain reaction assay throughout our study. Peak and
      trough plasma amino acid concentrations were assessed on day 30. RESULTS: Fewer
      cats and eyes were affected by conjunctivitis, and onset of clinical signs of
      infection was delayed on average by 7 days in cats receiving L-lysine, compared
      with cats in the control group; however, significant differences between groups
      were not demonstrated. Significantly fewer viral shedding episodes were
      identified in the treatment group cats, compared with the control group cats,
      after rehousing but not following corticosteroid-induced viral reactivation. Mean
      plasma L-lysine concentration was significantly increased at 3 hours but not at
      24 hours after L-lysine administration. Plasma arginine concentration was not
      significantly altered. CONCLUSIONS AND CLINICAL RELEVANCE: Once daily oral
      administration of 400 mg of L-lysine to cats latently infected with FHV-1 was
      associated with reduced viral shedding following changes in housing and husbandry
      but not following corticosteroid administration. This dose caused a significant
      but short-term increase in plasma L-lysine concentration without altering plasma
      arginine concentration or inducing adverse clinical effects.

PMID- 12518877
TI  - Evaluation of transcutaneous Doppler ultrasonography for the measurement of blood
      flow in the femoral artery of pigs.
AB  - OBJECTIVE: To compare measurements of blood flow in the common femoral artery
      obtained by duplex Doppler ultrasonography (DDU) and a reference ultrasonic
      transit-time flow (TTF) method and to examine the impact of Doppler spectral
      waveform measurement techniques on volumetric estimates. ANIMALS: 5 healthy
      female pigs. PROCEDURES: Femoral arterial blood flow was measured simultaneously
      in anesthetized pigs by use of a TTF probe (left femoral artery) and
      transcutaneous DDU (right femoral artery). A range of flow states was induced
      pharmacologically by using xylazine, bradykinin, dobutamine, and isoflurane.
      Volumetric blood flow was calculated from DDU waveforms, using the product of the
      flow velocity integral (FVI), the cross-sectional vessel area, and heart rate.
      Three calculations of FVI were obtained by manually tracing the Doppler spectral
      envelopes at the outer envelope, the modal, and the inner envelope of the
      spectral dispersion pattern. Data analysis included calculation of Pearson
      correlation coefficients and Bland-Altman limits of agreement. RESULTS: Blood
      flow measured by DDU was more closely correlated with TTF measurements when the
      modal or inner envelope tracing method was used (r, 0.76 and 0.78; limits of
      agreement, -100 to 54.2 and -48.5 to 770 mL/min, respectively). Limits of
      agreement for the outer envelope tracing method were -238.5 to 64 mL/min.
      CONCLUSIONS AND CLINICAL RELEVANCE: Transcutaneous DDU is a reliable noninvasive
      technique for measuring blood flow in the femoral artery of pigs over a range of
      flow states. Tracing the inner envelope of the Doppler spectral dispersion
      pattern provided the best estimate of blood flow in this study.

PMID- 12518878
TI  - Analgesic and systemic effects of ketamine, xylazine, and lidocaine after
      subarachnoid administration in goats.
AB  - OBJECTIVE: To determine the effects of ketamine hydrochloride, xylazine
      hydrochloride, and lidocaine hydrochloride after subarachnoid administration in
      goats. ANIMALS: 6 healthy goats. PROCEDURE: In each goat, ketamine (3 mg/kg),
      xylazine (0.1 mg/kg), lidocaine (2.5 mg/kg), and saline (0.9% NaCI) solution were
      injected into the subarachnoid space between the last lumbar vertebra and first
      sacral vertebra (time 0). Analgesic, ataxic, sedative, cardiovascular, and
      respiratory effects and rectal temperature were evaluated before (baseline) and
      2, 5, 10, 15, and 30 minutes after administration and at 30-minute intervals
      thereafter as needed. RESULTS: Administration of anesthetics induced varying
      degrees of analgesia. Onset of the analgesic effect was more delayed for xylazine
      (mean +/- SD, 9.5 +/- 2.6 minutes) than for ketamine (6.7 +/- 2.6 minutes) or
      lidocaine (3.5 +/- 1.2 minutes). Duration of analgesia induced by xylazine (88.3
      +/- 15 minutes) was twice as long as the duration of analgesia induced by
      ketamine (48.8 +/- 13.5 minutes) but similar to that induced by lidocaine (66.5
      +/- 31 minutes). Xylazine induced bradycardia, whereas ketamine caused a
      nonsignificant increase in heart rate. Xylazine induced a reduction in arterial
      pressure, whereas ketamine or lidocaine did not affect arterial pressure.
      CONCLUSIONS AND CLINICAL RELEVANCE: Subarachnoid administration of xylazine in
      goats resulted in longer duration of analgesia of the tail, perineum, hind limbs,
      flanks, and caudodorsal rib areas than administration of ketamine or lidocaine.
      However, xylazine caused bradycardia and respiratory depression. Additional
      studies are needed to determine whether the analgesia would be sufficient to
      allow clinicians to perform surgical procedures.

PMID- 12518880
TI  - Effect of passive immunity on the development of a protective immune response
      against bovine viral diarrhea virus in calves.
AB  - OBJECTIVE: To determine whether passively acquired antibodies prevent development
      of a protective immune response to live virus in calves. ANIMALS: 18 calves.
      PROCEDURES: Calves were caught immediately after birth and tested free of bovine
      viral diarrhea virus (BVDV) and serum antibodies against BVDV. Within 48 hours,
      12 calves were fed colostrum that contained antibodies against BVDV and 6 calves
      received BVDV antibody free milk replacer. Three milk replacer fed and 6
      colostrum fed calves were exposed to virulent BVDV2-1373 at 2 to 5 weeks of life
      when passively acquired serum antibody titers were high. After serum antibody
      titers against BVDV had decayed to undetectable concentrations (at 7 to 9 months
      of age), the 3 remaining milk replacer fed calves, 6 colostrum fed calves
      previously exposed to BVDV2-1373, and 6 colostrum fed calves that had not been
      exposed to the virus were inoculated with BVDV2-1373. RESULTS: Passively acquired
      antibodies prevented clinical disease in inoculated colostrum fed calves at 2 to
      5 weeks of life. Serum antibody titers did not increase in these calves following
      virus inoculation, and serum antibody titers decayed at the same rate as in
      noninoculated colostrum fed calves. Inoculated colostrum fed calves were still
      protected from clinical disease after serum antibody titers had decayed to
      nondetectable concentrations. Same age colostrum fed calves that had not been
      previously exposed to the virus were not protected. CONCLUSIONS AND CLINICAL
      RELEVANCE: A protective immune response was mounted in calves with passive
      immunity, but was not reflected by serum antibodies titers. This finding has
      implications for evaluating vaccine efficacy and immune status.

PMID- 12518879
TI  - Estimation of receiver-operating characteristic curves to determine accuracy of a
      competitive enzyme-linked immunosorbent assay for the serodiagnosis of Brucella
      infection in domestic water buffalo (Bubalus bubalis) and cattle.
AB  - OBJECTIVE: To estimate receiver-operating characteristic (ROC) curves for a
      competitive ELISA (c-ELISA) that is used in serodiagnosis of brucellosis in water
      buffalo and cattle, to determine the most appropriate positive cutoff value for
      the c-ELISA in confirmation of infection, and to evaluate species differences in
      c-ELISA function. SAMPLE POPULATION: Sera from 4 herds of cattle (n = 391) and 4
      herds of water buffalo (381). PROCEDURE: Serum samples were evaluated for
      Brucella-specific antibodies by use of a c-ELISA. On the basis of previous
      serologic test results, iterative simulation modeling was used to classify
      animals as positive or negative for Brucella infection without the use of a gold
      standard. Accuracy of c-ELISA for diagnosis of infection was compared between
      cattle and water buffalo by comparison of areas under ROC curves. RESULTS: A
      positive cutoff value of 30% inhibition for c-ELISA yielded sensitivity and
      specificity estimates, respectively, of 83.9 and 92.6% for cattle and 91.4 and
      95.4% for water buffalo. A positive cutoff value of 35% inhibition yielded
      sensitivity and specificity estimates, respectively, of 83.9 and 96.2% for cattle
      and 88.0 and 974% for water buffalo. Areas under ROC curves were 0.94 and 0.98
      for cattle and water buffalo, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      ROC curves can be estimated by use of iterative simulation methods to determine
      optimal cutoff values for diagnostic tests with quantitative outcomes. A cutoff
      value of 35% inhibition for the c-ELISA was found to be most appropriate for
      confirmation of Brucella infection in cattle and water buffalo.

PMID- 12518881
TI  - Influence of age of horse on results of quantitative electromyographic needle
      examination of skeletal muscles in Dutch Warmblood horses.
AB  - OBJECTIVE: To determine the influence of age on results of quantitative analysis
      of electromyographic (EMG) needle examination in the subclavian, triceps, and
      lateral vastus muscles of Dutch Warmblood horses. ANIMALS: 7 healthy young Dutch
      Warmblood horses (range, 13 to 18 months old), 7 healthy adult Dutch Warmblood
      horses (range, 4 to 10 years old), and 7 healthy elderly Dutch Warmblood horses
      (range, 18 to 21 years old). PROCEDURE: An EMG needle examination was performed
      to evaluate insertional activity, spontaneous activity, and motor unit action
      potential (MUAP) variables. Although all horses were conscious, young horses were
      sedated prior to examination. RESULTS: Mean insertional activity in young horses
      was significantly lower than in elderly horses. Pathologic spontaneous activity
      was rarely found in young and adult horses but was frequently evident in all
      muscles in all elderly horses. The MUAP duration and amplitude were significantly
      lower in all muscles of young horses, compared with values for adult and elderly
      horses. The MUAP duration and number of phases and turns were significantly lower
      in adult horses than in elderly horses. Group differences for percentages of
      polyphasic and complex MUAPs were also found. The 95% confidence intervals for
      MUAP duration, MUAP amplitude, and number of phases and turns for the subclavian,
      triceps, and lateral vastus muscles were significantly lower in young horses than
      in adult or elderly horses. CONCLUSIONS AND CLINICAL RELEVANCE: Age of the horse
      being examined should be considered when EMG examination is performed.

PMID- 12518882
TI  - Evaluation of ground reaction forces produced by chickens walking on a force
      plate.
AB  - OBJECTIVE: To evaluate the use of a force plate as a method for objective gait
      analysis in adult poultry, to characterize ground reaction forces (GRFs) produced
      in adult chickens during normal walking, and to assess the variability of GRFs.
      ANIMALS: 18 clinically normal 5-month-old Brown Leghorn hens. PROCEDURE:
      Vertical, craniocaudal, and mediolateral GRFs were measured as hens walked across
      a standard force plate embedded in the middle of a runway. RESULTS: All GRFs were
      significantly affected by speed, and variability was high. With increasing speed,
      overall stance time decreased, but the percentage of stance time spent in braking
      or propulsion remained approximately equal. There was an overall increase in
      maximum propulsion force, which was produced at a greater rate over a shorter
      time; thus, propulsion integral decreased. Maximum braking forces and braking
      integrals were variable, but the rate at which the forces were generated
      increased. Mediolateral forces were 2 to 3 times greater in hens than values that
      have been reported for other species. CONCLUSIONS AND CLINICAL RELEVANCE: A
      standard force plate can be used to objectively measure GRFs in walking adult
      hens; however, the large variation in the data suggests that the technique in its
      current form would be of limited clinical use. Overall, vertical and craniocaudal
      forces had similar characteristics to those of other species, whereas
      mediolateral forces were found to be much greater in chickens than for other
      species.

PMID- 12518883
TI  - New approach for quantitative assessment of articular cartilage degeneration in
      horses with osteoarthritis.
AB  - OBJECTIVE: To evaluate a modified digital imaging technique for quantitative
      assessment of the grade of osteoarthritis across the proximal articular surface
      of the first phalanx in horses. SAMPLE POPULATION: 6 metacarpophalangeal (fet
      lock) joint specimens from 6 horses with various stages of osteoarthritis.
      PROCEDURE: First phalanx specimens, together with 4 gray scale reference
      calibration targets, were positioned in a bath with the proximal articular
      cartilage surface submerged in saline (0.9% NaCl) solution. Digital images were
      obtained from the articular surface before and after staining with Indian ink.
      Computer-controlled gray level analysis of the nonstained and Indian ink-stained
      cartilage surfaces and gray scale reference calibration targets was performed by
      use of the mean pixel value (based on 255-gray scale). An increase in the mean
      pixel value after staining was used to calculate the cartilage degeneration index
      (CDI). RESULTS: The CDI of the proximal articular cartilage surface of the first
      phalanx specimens ranged from 9.2 +/- 5.7 (early stage osteoarthritis) to 41.5 +/
      3.6% (late stage osteoarthritis). The effect of repeating the measurement 6
      times in nonstained (including repositioning) and stained specimens (including
      repositioning and restaining) was not significant. Up to 10 measurements of
      nonstained specimens could be made without refreshing the bath solution. In
      stained specimens, mean gray level increased significantly after the sixth
      measurement. CONCLUSIONS AND CLINICAL RELEVANCE: The modified digital imaging
      technique allowed quantitative assessment of cartilage degeneration across the
      articular cartilage surface. The CDI is the first quantitative measure for
      osteoarthritis-induced cartilage degeneration over an entire joint surface in
      horses.

PMID- 12518884
TI  - Effects of topical application of antimicrobials and bandaging on healing and
      granulation tissue formation in wounds of the distal aspect of the limbs in
      horses.
AB  - OBJECTIVE: To determine whether povidone iodine ointment or 2 forms of silver
      sulfadiazine applied topically to wounds of the distal aspect of the limbs in
      horses affect the rate of second intention healing and to evaluate the additional
      influence of bandaging with these antimicrobials on granulation tissue formation.
      ANIMALS: 6 healthy adult horses. PROCEDURE: Six standardized 2.5-cm2 skin
      wounds/horse were distributed between the dorsomedial surfaces of the metacarpi
      and metatarsi. One of the following 6 treatments was applied to each wound: 1%
      silver sulfadiazine cream with bandage, 1% silver sulfadiazine slow-release
      matrix with bandage, 1% silver sulfadiazine slow-release matrix without bandage,
      povidone-iodine ointment with bandage, untreated control with bandage, and
      untreated control without bandage. Wound area, granulation tissue area, and
      perimeter were measured by use of planimetry software applied to digital images.
      Exuberant granulation tissue was excised when present. Days until healing, rate
      of healing parameter, rate of contraction, and epithelialization were compared
      among wound treatment groups. RESULTS: Healing parameters and mean days to
      healing did not differ significantly among any of the wound treatment groups.
      Percentage wound contraction and rate of epithelialization were similar among
      wound treatments. All bandaged wounds produced exuberant granulation tissue,
      which was surgically excised; none of the unbandaged wounds produced exuberant
      granulation tissue. CONCLUSIONS AND CLINICAL RELEVANCE: When exuberant
      granulation tissue is removed, rates of epithelialization and wound contraction
      were not different among wound treatment groups, whether bandaged or unbandaged.
      Topical application of 1% silver sulfadiazine slow-release matrix on unbandaged
      wounds induced the same result as medications applied beneath bandages, but
      without exuberant granulation tissue formation.

PMID- 12518885
TI  - Comparison between invasive hemodynamic measurements and noninvasive assessment
      of left ventricular diastolic function by use of Doppler echocardiography in
      healthy anesthetized cats.
AB  - OBJECTIVE: To compare Doppler echocardiographic variables of left ventricular
      (LV) function with those obtained invasively via cardiac catheterization under a
      range of hemodynamic conditions. ANIMALS: 7 healthy anesthetized cats (1 to 3
      years of age). PROCEDURE: Cats were anesthetized and instrumented to measure the
      time constant of isovolumic relaxation (tau [tau]), LV end-diastolic pressure
      (LVEDP), peak negative and positive rate of change of LV pressure, arterial blood
      pressure, and cardiac output. Echocardiographic variables of diastolic function
      (isovolumic relaxation time [IVRT], early LV flow propagation velocity [Vp],
      transmitral and pulmonary venous flow velocity indices, and LV tissue Doppler
      imaging indices) were measured simultaneously over a range of hemodynamic states
      induced by treatments with esmolol, dobutamine, cilobradine, and volume loading.
      Correlation between invasive and noninvasive measures of LV filling was
      determined by univariate and multivariate regression analyses. RESULTS:
      Significant correlations were found between tau and IVRT, peak Vp, peak late
      transmitral flow velocity, and peak systolic pulmonary venous flow velocity. A
      significant correlation was found between LVEDP and early diastolic transmitral
      flow velocity (peak E) and the ratio of peak E to peak Vp, but not between LVEDP
      and peak Vp. CONCLUSIONS AND CLINICAL RELEVANCE: IVRT and Vp can be used as
      noninvasive indices of LV relaxation; Vp was independent of preload and heart
      rate in this study. The E:Vp ratio may be useful as an indicator of LV filling
      pressure.

PMID- 12518886
TI  - Evaluation of lysozyme and lactoferrin in lacrimal and other ocular glands of
      bison and cattle and in tears of bison.
AB  - OBJECTIVE: To evaluate lactoferrin and lysozyme content in various ocular glands
      of bison and cattle and in tears of bison. SAMPLE POPULATION: Tissues of ocular
      glands obtained from 15 bison and 15 cattle and tears collected from 38 bison.
      PROCEDURE: Immunohistochemical analysis was used to detect lysozyme and
      lactoferrin in formalin-fixed, paraffin-embedded sections of the ocular glands.
      Protein gel electrophoresis was used to analyze ocular glands and pooled bison
      tears by use of a tris-glycine gel and SDS-PAGE. Western blotting was used to
      detect lactoferrin and lysozyme. RESULTS: Immunohistochemical staining for
      lactoferrin was evident in the lacrimal gland and gland of the third eyelid in
      cattle and bison and the deep gland of the third eyelid (Harder's gland) in
      cattle. Equivocal staining for lactoferrin was seen for the Harder's gland in
      bison. An 80-kd band (lactoferrin) was detected via electrophoresis and western
      blots in the lacrimal gland and gland of the third eyelid in cattle and bison,
      Harder's glands of cattle, and bison tears. An inconsistent band was seen in
      Harder's glands of bison. Lysozyme was not detected in the lacrimal gland of
      cattle or bison with the use of immunohistochemical analysis or western blots.
      Western blots of bison tears did not reveal lysozyme. CONCLUSIONS AND CLINICAL
      RELEVANCE: Distribution of lactoferrin and a lack of lysozyme are similar in the
      lacrimal gland of cattle and bison. Differences in other tear components may be
      responsible for variability in the susceptibility to infectious corneal diseases
      that exists between bison and cattle.

PMID- 12518887
TI  - Oral bioavailability and pharmacokinetic characteristics of ketoprofen
      enantiomers after oral and intravenous administration in Asian elephants (Elephas
      maximus).
AB  - OBJECTIVE: To assess oral bioavailability (F) and pharmacokinetic characteristics
      of the R- and S-enantiomers of ketoprofen administered IV and orally to captive
      Asian elephants (Elephas maximus). ANIMALS: 5 adult Asian elephants. PROCEDURE:
      Elephants received single treatments of racemic ketoprofen at a dose of 2.2
      mg/kg, administered IV and orally, in a complete crossover design. Blood samples
      were collected at intervals during the 24 hours following treatment. At least 4
      weeks elapsed between drug administrations. Samples were analyzed for R- and S
      ketoprofen with a validated liquid chromatography-mass spectroscopic assay.
      Pharmacokinetic parameters were determined by use of noncompartmental analysis.
      RESULTS: The enantiomers of ketoprofen were absorbed well after oral
      administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen.
      Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of
      administration and enantiomer. The area under the concentration-time curve, mean
      residence time, apparent volume of distribution, plasma clearance, and maximum
      plasma concentration values were all significantly different between the 2
      enantiomers for both routes of administration. CONCLUSIONS AND CLINICAL
      RELEVANCE: Ketoprofen has a long terminal half-life and complete absorption in
      this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1
      mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use
      in Asian elephants, although the safety and efficacy of ketoprofen during long
      term administration in elephants have not been determined.

PMID- 12518888
TI  - Radiographic findings before and after oral administration of a magnet in cows
      with traumatic reticuloperitonitis.
AB  - OBJECTIVE: To evaluate by use of radiography the efficacy of oral administration
      of magnets in the treatment of traumatic reticuloperitonitis in cows. ANIMALS: 90
      cows referred because of indigestion. PROCEDURE: Radiography of the reticulum was
      performed. In all cows, radiographic findings revealed a metal foreign body in
      the reticulum. A magnet was administered orally, and the reticulum was again
      radiographed to assess the position of the magnet and to determine whether the
      foreign body was attached to the magnet. RESULTS: The magnet was observed in the
      reticulum in 75 cows and in the cranial aspect of the dorsal sac of the rumen in
      9 cows; in 6 cows, the magnet was not observed. The foreign body was fully
      attached to the magnet in 49 cows. In 6 cows, the foreign body was in contact
      with the magnet but still penetrated the reticulum. In 24 cows, the foreign body
      did not contact the magnet, and in 11 cows, it was not clear whether the foreign
      body was attached to the magnet. A foreign body at an angle to the ventral aspect
      of the reticulum of > 3 degrees was less likely to become attached to a magnet,
      compared with a foreign body situated horizontally on the ventral aspect of the
      reticulum. A foreign body with no contact to the ventral aspect of the reticulum
      or a perforating foreign body was also less likely to become attached to a
      magnet. CONCLUSIONS AND CLINICAL RELEVANCE: Position of the foreign body within
      the reticulum greatly influences the efficacy of treatment with a magnet.

PMID- 12518889
TI  - Anoikis: roadblock to cell transplantation?
AB  - Cell therapy, in particular liver cell transplantation, holds great therapeutic
      potential and is partially hindered by the high rate of apoptosis during cell
      isolation, cryopreservation, and engraftment. Apoptosis occurring due to cell
      detachment from the extracellular matrix is a phenomenon termed "anoikis." The
      purpose of this review is to describe signaling mechanisms pertinent to anoikis
      in both immortalized cell lines, but particularly in primary normal epithelial
      cells. The mechanisms described include integrin signaling and survival
      molecules, caspase activation, and the role of mitochondrial proteins in anoikis.
      Strategies to prevent anoikis during isolation and cryopreservation of
      hepatocytes are discussed.

PMID- 12518890
TI  - Monkey embryonic stem cell lines expressing green fluorescent protein.
AB  - The major limitation of nonhuman primate (NHP) embryonic stem (ES) cell research
      is inefficient genetic modification and limited knowledge of differentiation
      mechanisms. A genetically modified NHP-ES cell with biomarkers, such as green
      fluorescent protein (GFP), that allow noninvasive monitoring of transgenic cells,
      is a useful tool to study cell differentiation control during preimplantation and
      fetal development, which also plays a crucial role in the development of cell
      transplantation medicine. Here we report the establishment of transgenic NHP-ES
      cell lines that express GFP without jeopardizing their pluripotency, which was
      confirmed by in vitro and in vivo differentiation. These GFP-expressing ES cells
      reproducibly differentiated into embryoid bodies, neural cells, and cardiac
      myocytes. They formed teratoma composed of tissues derived from the three
      embryonic germ layers when transplanted into severe combined immunodeficient
      disease (SCID) mice. GFP expression was maintained in these differentiated cells,
      suggesting that these cells were useful for cell transplantation experiments.
      Furthermore, we showed that these ES cells have the ability to form chimeric
      blastocysts by introducing into the early preimplantation stage NHP embryo.

PMID- 12518891
TI  - The release of excitatory amino acids, dopamine, and potassium following
      transplantation of embryonic mesencephalic dopaminergic grafts to the rat
      striatum, and their effects on dopaminergic neuronal survival in vitro.
AB  - A major limitation to the effectiveness of grafts of fetal ventral mesencephalic
      tissue for parkinsonism is that about 90-95% of grafted dopaminergic neurones
      die. In rats, many of the cells are dead within 1 day and most cell death is
      complete within 1 week. Our previous results suggest that a major cause of this
      cell death is the release of toxins from the injured CNS tissue surrounding the
      graft, and that many of these toxins have dissipated within 1 h of inserting the
      grafting cannula. In the present experiments we measured the change over time in
      the concentration of several potential toxins around an acutely implanted
      grafting cannula. We also measured the additional effect of injecting suspensions
      of embryonic mesencephalon, latex microspheres, or vehicle on these
      concentrations. Measurements of glutamate, aspartate, and dopamine by
      microdialysis showed elevated levels during the first 20-60 min, which then
      declined to baseline. In the first 20 min glutamate levels were 10.7 times,
      aspartate levels 5 times, and dopamine levels 24.3 times baseline. Potassium
      levels increased to a peak of 33 +/- 10.6 mM 4-5 min after cannula insertion,
      returning to baseline of <5 mM by 30 min. Injection of cell suspension, latex
      microspheres, or vehicle had no significant effect on these levels. We then
      assayed the effect of high concentrations of glutamate, aspartate, dopamine, and
      potassium on dopaminergic neuronal survival in E14 ventral mesencephalic
      cultures. In monolayer cultures only dopamine at 200 microM showed toxicity. In
      three-dimensional cultures only the combination of raised potassium, dopamine,
      glutamate, and aspartate together decreased dopaminergic neuronal survival. We
      conclude that toxins other than the ones measured are the main cause of
      dopaminergic cell death after transplantation, or the effects of the toxins
      measured are enhanced by anoxia and metabolic challenges affecting newly inserted
      grafts.

PMID- 12518892
TI  - Effects of antioxidant pretreatment on the survival of embryonic dopaminergic
      neurons in vitro and following grafting in an animal model of Parkinson's
      disease.
AB  - The effect of pretreating cell suspensions of embryonic rat ventral mesencephala
      (VM) with antioxidant combinations on the survival of dopaminergic (DA) neurons
      was studied in vitro and following transplantation into the unilateral 6
      hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. The in vitro
      experiments examined the effects of two thiol antioxidants, N-acetyl-L-cysteine
      (NAC) and reduced glutathione (GSH), and a member of the lazaroid family of 21
      aminosteroids, U-83836E, singly and in combination, on survival of DA neurons
      derived from dissociated E14 rat VM tissue. For in vivo studies, cell suspensions
      were pretreated with combinations of NAC, GSH, and U-83836E prior to
      transplanting into 6-OHDA-lesioned rats to investigate whether DA neuron survival
      could be further improved. NAC, GSH, and U-83836E individually increased DA
      neuron survival in vitro and a combination of all three resulted in the greatest
      survival. In vivo, pretreatment with U-83836E alone resulted in a significantly
      greater reduction in amphetamine-induced rotation 6 weeks postgrafting compared
      with a control group receiving nontreated graft tissue. This functional effect
      correlated with a significant improvement in DA neuron survival 6 weeks
      postgrafting. The thiol combination pretreatment of NAC and GSH, and the triple
      combination of NAC, GSH, and U-83836E, however, failed to improve both functional
      recovery and DA neuron survival when compared with the nontreated control grafts.

PMID- 12518894
TI  - Dynamics of the early immune cellular reactions after myogenic cell
      transplantation.
AB  - The role of immune cells in the early donor cell death/survival following
      myoblast transplantation is confusing, one of the reasons being the lack of data
      about the immune reactions following cell transplantation. We used outbred mice
      as hosts for transplantation of primary cultured muscle cells and T-antigen
      immortalized myoblasts. The host muscles were analyzed 1 h to 7 days after cell
      injection. No net loss of the donor primary cultured cell population was observed
      in this period. The immune cellular reaction in this case was: 1) a brief (<48 h)
      neutrophil invasion; 2) macrophage infiltration from days 1 to 7; 3) a specific
      response involving CTL and few NK cells (days 6 and 7), preceded by a low CD4+
      cell infiltration starting at day 3. In contrast, donor-immortalized myoblasts
      completely disappeared during the 7-day follow-up. In this case, an intense
      infiltration of CTL and macrophages, with moderate CD4+ infiltration and lower
      amounts of NK cells, was observed starting at day 2. The nonspecific immune
      response at days 0 and 1 was similar for both types of donor cells. The present
      observations set a basis to interpret the role of immune cells on the early
      death/survival of donor cells following myoblast transplantation.

PMID- 12518893
TI  - Intracerebral transplantation and successful integration of astrocytes following
      genetic modification with a high-capacity adenoviral vector.
AB  - To investigate the ability of genetically modified astrocytes to integrate into
      adult rat brain, two spontaneously immortalized cell lines and the allogenic
      nontumorigenic glioma cell line F98 were transduced with a high-capacity
      adenoviral vector (HC-Adv) expressing the EGFP gene from the hCMV promoter. In
      organotypic slice cultures the transduced astrocytes were shown to integrate into
      the brain tissue. Following transplantation of the transduced astrocytes into the
      striatum of adult rats, the transplanted cells survived at least for 6 weeks,
      continuously expressed the EGFP transgene, in close neighborhood with cells of
      the recipient tissue executing their differentiation capacity along the glial
      lineage. Thus, HC-Adv transduced astrocytes are promising vehicles to locally
      deliver therapeutic proteins for the treatment of neurodegenerative diseases.

PMID- 12518895
TI  - Mechanisms of alloimmune tolerance associated with mixed chimerism induced by
      vascularized bone marrow transplants.
AB  - Rat limb allograft recipients represent surgically induced, immediately
      vascularized bone marrow transplant (VBMT) chimeras. The majority of these
      chimeras undergo tolerance while a minority develop graft versus host disease
      (GVHD). T-cell chimerism and associated mechanisms of cellular immune
      nonresponsiveness were investigated in tolerant VBMT chimeras. A strong
      correlation (p < 0.01) was observed between the clinical onset of GVHD and levels
      of donor T-cell chimerism approximating or greater than 50%. However, stable
      mixed chimerism was associated with tolerance. In conclusion, three major
      sequential mechanisms of immune nonresponsiveness were elucidated in tolerant
      VBMT chimeras over time and included development of nonspecific suppressor cells
      (which potentially represent natural suppressor cells), maturation of antigen
      specific suppressor cell circuits, and eventually putative clonal inactivation.

PMID- 12518896
TI  - Proliferative and cytokine responses in CTLA4-Ig-treated diabetic NOD mice
      transplanted with microencapsulated neonatal porcine ICCs.
AB  - Our goal is to develop effective islet xenografts for treating human diabetes. We
      have studied microencapsulated neonatal porcine islet cell clusters (ICCs)
      transplanted intraperitoneally in spontaneously diabetic NOD mice, where they
      function to maintain normoglycemia in the autoimmune host. Nonencapsulated
      neonatal porcine ICCs functioned for 4.5 +/- 0.5 days before being rejected;
      encapsulation prolonged graft function to 17 +/- 2 days. CTLA4-Ig treatment did
      not enhance the survival of nonencapsulated ICCs. However, CTLA4-Ig treatment
      significantly extended the function of encapsulated ICCs to 73 +/- 5 days.
      Histological analyses demonstrated a profuse pericapsular cellular reaction
      associated with rejection of encapsulated islet xenografts in untreated mice,
      while this reaction was significantly reduced in CTLA4-Ig-treated mice. To study
      mechanisms of xenograft rejection in this model, we analyzed proliferative
      responses to neonatal porcine ICCs and cytokines present in the peritoneal
      cavities of transplanted mice. Spleen cells from both CTLA4-Ig-treated and
      untreated rejecting NODs exhibited vigorous proliferation in the absence of
      antigenic stimulation, suggesting prior activation in vivo, while splenocytes
      from CTLA4-Ig-treated NODs with functioning grafts had low proliferative levels,
      equal to controls. Islet-specific proliferation was not detected in islet
      rejecting mice, perhaps due to their high background levels. With the exception
      of elevated IL-6 levels, empty capsules did not provoke a significant peritoneal
      cytokine response compared with sham surgery or untransplanted control mice.
      However, IL-5, IL-12, TGF-beta, and IL-1beta were significantly elevated in NODs
      receiving encapsulated neonatal porcine ICCs compared with untransplanted
      controls. There were no significant differences between peritoneal cytokine
      concentrations in CTLA4-Ig-treated mice with long-term functioning grafts
      compared to mice that rejected grafts at earlier time points. We conclude that
      the combination of donor islet microencapsulation and brief treatment of the
      recipient with co-stimulatory blockade delays sensitization of the host, possibly
      by altering mechanism(s) for recruitment and/or activation of host effector
      cells.

PMID- 12518897
TI  - Decreased survival of islet allografts in rats with advanced chronic
      complications of diabetes.
AB  - Successful islet transplantation has been possible in experimental animals in
      contrast to humans. One difference between animal models of diabetes and human
      islet transplantation is the presence of advanced chronic complications in
      humans. Even longer-term follow-up of islet transplantation in humans according
      to the Edmonton protocol suggests that advanced chronic complications may
      adversely affect allograft survival with the glucocorticoid-free
      immunosuppressive regimen as well. We developed a rat model of chronic
      complications of diabetes and compared islet allograft survival in rats with
      advanced chronic complications to age-matched control rats with acute onset
      diabetes. Islets were transplanted at either the renal supcapsular, intrahepatic,
      or intramuscular location. The survival of islet allografts in rats with chronic
      complications was decreased at all sites compared with the age-matched controls.
      The best survival in the rats with advanced chronic complications occurred at the
      renal subcapsular site. Blood sugar measurements indicated impaired glucose
      tolerance in most of the rats with chronic complications and surviving renal
      subcapsular islet allograft. Histological and gross examination of the surviving
      renal subcapsular islet allografts indicated disordered angiogenesis in the rats
      with chronic complications. Rats with successful intrahepatic islet allografts
      and the respective age-matched controls had comparable blood sugars. Survival of
      islet allografts at the intramuscular site was poor in rats with chronic
      complications or acute onset diabetes. We conclude that the structural or
      metabolic abnormalities associated with chronic poor control of diabetes impair
      islet allograft survival and function. This should be considered as a possible
      explanation for failure of islet allograft survival in human islet
      transplantation.

PMID- 12518898
TI  - Co-stimulatory molecules in islet xenotransplantation: CTLA4Ig treatment in CD40
      ligand-deficient mice.
AB  - Previous work has demonstrated that short-term systemic administration of
      cytotoxic T lymphocyte antigen-4 (CTLA-4) Ig blocks human pancreatic islet
      xenograft rejection in mice and induces long-term, donor-specific tolerance,
      whereas studies on pig pancreatic islet rejection in mice have failed to
      demonstrate a role for CTLA4Ig in preventing rejection. Treatment with anti-CD40
      ligand (L) monoclonal antibodies alone is somewhat effective in prolonging the
      survival of islet xenografts, but ineffective when applied to skin xenografts.
      However, simultaneous blockade of the CD28 and CD40 co-stimulatory pathways
      prolongs the survival of pig skin on recipient mice. To evaluate the role of CD28
      and CD40 co-stimulatory pathways in pig islet-like cell cluster (ICC) xenograft
      rejection in mice, CD40L-deficient mice transplanted with fetal porcine ICCs were
      given posttransplant treatment with human (h) CTLA4Ig or a human IgG1 chimeric
      mAb (hL6). Xenografts were evaluated 6 or 12 days after transplantation. Fetal
      porcine ICC xenografts were protected from rejection in hCTLA4Ig-treated CD40L
      deficient mice, whereas xenograft rejection persisted in untreated CD40L
      deficient mice. Simultaneous blockade of the CD28 and CD40 co-stimulatory
      pathways is mandatory to inhibit ICC xenograft rejection in the pig-to-mouse
      model, because the CD28 and CD40 co-stimulatory pathways seem capable of
      efficiently substituting for one another.

PMID- 12518899
TI  - Insulin treatment of mice recipients preserves beta-cell function in porcine
      islet transplantation.
AB  - Encapsulation of islets of Langerhans confers protection against cell-mediated
      immune destruction and so should allow the transplantation of islets without
      immunosuppression. Xenotransplantation of encapsulated islets of Langerhans might
      therefore help overcome problems of human organ donor shortage. Given that islets
      exposed to sustained hyperglycemia show impaired beta-cell function, we set out
      to determine whether recipient treatment with insulin could improve
      transplantation success rate. Islets of Langerhans were obtained from Specific
      Germ-Free (SPF) pig pancreas and cultured overnight. Islets were encapsulated in
      AN69 fibers and implanted into the peritoneal cavity of diabetic mice. A group of
      implanted mice was treated with exogenous insulin from day 3 to day 7 after
      grafting. Islet implantation depressed plasma glucose in all the mice, both
      insulin treated and untreated. Glycemia slowly increased in the non-insulin
      treated mice, whereas the decrease observed in the insulin-treated mice was
      maintained until day 29 of follow-up. We found significant differences between
      the two groups (p < 0.05 at day 18 and day 20, p < 0.001 at day 23 and day 29).
      No improvement of hyperglycemia was observed in diabetic mice implanted with
      empty fibers. When islet-containing fibers were removed from the peritoneal
      cavity of mice 1 month after the graft plasma glucose increased markedly. We
      demonstrate that treatment of recipients with exogenous insulin in the immediate
      posttransplantation period has a positive effect on beta-cell function in
      transplanted macroencapsulated porcine islets.

PMID- 12518900
TI  - Autoimmune haemolytic anaemia: pattern of presentation and management outcome in
      a Nigerian population: a ten-year experience.
AB  - Autoimmune haemolytic anaemia (AHA) is one of the commonest autoimmune disorders
      of man. It is characterised by the binding of anti-erythrocyte autoantibodies to
      red blood cells and destruction of the coated cells in the reticulo-endothelial
      system. Autoimnmune disorders are said to be rare in indigenous African
      population, probably due to the widespread infectious diseases, which impair
      host's T-cell immunity. This study is therefore aimed at investigating the
      pattern of presentation and management outcome of patients with AHA seen over a
      period of 10 years (June 1988 to May 1998) at the Obafemi Awolowo University
      Teaching Hospitals Complex, Ile-Ife. We retrospectively analysed the records of
      patients with respect to the clinical, haematological, biochemical and
      serological features of AHA seen within the study period. Diagnosis was based on
      laboratory features of haemolytic anaemia and/or a positive direct anti-human
      globulin (Coombs') test after excluding other causes of haemolytic anaemia.
      Treatment protocol and outcome were noted in all cases. We identified 13 patients
      with AHA (7 females, 6 males) aged 6-70 (median, 42) years. Six (42%) had
      secondary AHA and the remaining 8 presented with primary (idiopathic) AHA.
      Laboratory evidence of haemolysis (bone marrow erythroid hyperplasia and
      hyperbilirubinaemia) was found in all cases, while the direct Coomb's test was
      positive in 10 (76.9%) cases. All the patients had moderate-severe anaemia within
      the course of the disease, requiring blood transfusion. Remission was induced
      with prednisolone in all except three cases with secondary AHA who died of the
      primary disease before AHA could be controlled. Follow-up period post-remission
      ranged between 1 and 78 months. However, 2 (20%) are still being followed-up till
      the time of this report. This study agrees with the view that autoimmune
      disorders are not common in Nigerians, as documented for other Africans. It also
      shows that steroid therapy (prednisolone) is quite effective, especially, in
      idiopathic AHA, and that red cell transfusion could be useful in life-threatening
      anaemia.

PMID- 12518901
TI  - Concomitant injuries in 531 patients with maxillofacial fractures.
AB  - A ten-year review of five hundred and thirty one patients with facial fractures
      who sustained six hundred and forty eight associated injuries was presented. The
      male to female ratio was 2.7:1 and the highest incidence was in the 21-30 years
      age group. Road traffic accident was the commonest aetiology while the most
      frequently associated injury was soft tissue lacerations (71.0%). Neurological
      injuries constituted 9.9% of the total number of concomitant injuries. Other
      associated injuries seen were orthopaedic injuries 9.5%, ophthalmologic injuries
      6.6%, chest injuries 1.9%, abdominal injuries 0.6% and urological injuries 0.5%.
      It is mandatory that the surgical team should be organised in the treatment of
      patients with concomitant injuries coexisting with maxillofacial fractures.

PMID- 12518902
TI  - Pattern of intestinal parasites among hosptial patients at Ile-Ife.
AB  - Intestinal and extraintestinal parasitic diseases continue to constitute
      important public health problems in many developing African countries. While
      malaria continues to ravage the continent, the silent onslaught of intestinal
      helminthiases and protozoal infection seem not to relent. The objectives of this
      study was therefore to determine the prevalence of intestinal helminthic and
      protozoan infections and to determine the trends in intestinal parasitic
      infections. Results of laboratory investigations for parasitic infections during
      a three-year period in two succeeding decades (1988-90 and 1996-98) were
      analysed. During the two periods 4233 (65.1%) of 6504 and 2297 (63.1%) of 3641
      clinical specimens were respectively, positive for intestinal parasites. These
      results are very significant as determinants of the level of environmental and
      domiciliary hygiene. It is concluded that the findings should be of great concern
      to the local Authority Health Departments which should spur the government to
      concerted effort aimed at ameliorating the deplorable situation brought about by
      indiscriminate faecal disposal.

PMID- 12518903
TI  - Contamination levels of in-use disinfectants in a teaching hospital in Lagos,
      Nigeria.
AB  - In-use testing of the disinfectants; Hibitane (5% w/v Chlorhexidinegluconate),
      Hibiscrub (4% w/v Chlorhexidinegluconate), Savlon (3% w/v
      Chlorhexidine/Cetrimide), hydrogen peroxide (6% w/v hydrogen peroxide with
      stabilizer) and a common household bleach Jik (3.5% w/v sodium hypochlorite), was
      carried out over a two-month period at a university teaching hospital in Nigeria.
      Contamination levels were high with 82 (63.1%) of the 130 in-use disinfectants
      contaminated. However, a few of the stock solutions remained sterile. One hundred
      and thirty-four isolates were obtained of which 120 (91%) were gram-negative with
      Pseudomonas species being the commonest, constituting 67.2% of all the isolates.
      Gram-positive organisms made up the remaining 12 (9.0%) isolates. All the
      Pseudomonas spp. were resistant to gentamicin, ceftazidime, nalidixic acid and
      perfloxacin. Contributory factors for the high contamination levels were dilution
      of disinfectants with tap water, inadequate care of stock solution bottles and
      long storage of the diluted disinfectants in the wards.

PMID- 12518904
TI  - Need for preventive and interceptive orthodontic treatment in 3-5 year-old
      Nigerian children in two major cities.
AB  - There is a growing emphasis world-wide for early orthodontic treatment but in
      Nigeria there is very little information regarding the occlusal development in
      pre-school children reported. The need for preventive and interceptive
      intervention for malocclusion was studied in a sample of 563 Nigerian children
      (289 boys and 274 girls) aged 3-5 years. Orthodontic intervention was estimated
      to be needed in 12.8% of the children due to cross bite of the anterior or
      lateral segments. Education was needed in 12.5% of the children in cases of digit
      sucking, lip sucking and tongue thrusting. Extraction was indicated in 0.4% of
      children in cases of retained primary incisors causing displacement of the
      erupting successors. The need for further follow-up of occlusal development was
      noted in 1.4% of the children due to double primary teeth (0.4%), numerical
      variation of primary teeth (0.4%), crown dilaceration of a tooth (0.2%) and true
      class III skeletal malocclusion (0.4%).

PMID- 12518905
TI  - Prevalence of periodontal pocketing and tooth mobility according to tooth types
      in Nigerians--a pilot study.
AB  - The aim of the present study was to evaluate the occurrence of periodontal
      pocketing and tooth mobility according to the tooth types in the mouth. There is
      a paucity of knowledge concerning which tooth types are more prone to periodontal
      disease from the review of literature. The study sample comprised 255 subjects,
      age ranged 16 years to 74 years. These subjects were those referred to the
      Periodontology Clinic of the University College Hospital, Ibadan, Nigeria, for
      one form of periodontal disease or the other. All the teeth were tested for
      periodontal pocketing using William's periodontal probe (Astir Intermedica,
      Kensington, London) and for tooth mobility using the Miller's Mobility Index
      method. The study showed that prevalence of tooth mobility is in this descending
      order--lower incisors, upper incisors, upper first molars, upper second molars,
      lower first and second molar, the premolars and lastly, the canines with the
      least occurrence on the upper left canines. This order is slightly different for
      prevalence of periodontal pocketing. The teeth most affected by pocketing were
      the upper second molars, followed by upper first molars, lower second molars with
      the least being the canines. It is suggested that exceptional care be given to
      these most susceptible teeth for periodontal disease in the mouth in order to
      prevent the development of irreversible damage of the periodontium.

PMID- 12518906
TI  - Correlative study of 3 pain rating scales among obstetric patients.
AB  - The relationship between pain scores obtained on the Visual Analog Scale (VAS)
      the Box Numerical Scale (BNS) and Verbal Rating Scale (VRS) was studied. The
      subjects were 35 volunteer female patients who had their babies through caesarian
      section 1-3 days prior to the study. Demographic data and pain scores were
      collected through a questionnaire, which was available in both English and
      Yoruba, the two most commonly spoken languages in Ibadan where the study was
      carried out. Data were analysed using Pearson Product, Moment Correlation
      Coefficient, and One-way Analysis of Variance. Results indicated that there was
      no significant difference between the pain scores obtained on the 3 pain rating
      scales. Significant correlations existed between pain scores obtained on the VAS
      and VRS (r = 0.48, p = 0.003); VAS and BNS (r = 0.74, P = 0.000); BNS and VRS (r
      = 0.74, P = 0.000). High educational attainment improved correlation between the
      scales in this study. It was concluded that the three pain rating scales measure
      the same construct, and could be used for pain measurement in obstetrically
      related conditions in this environment.

PMID- 12518907
TI  - Neonatal septicaemia in Ilorin: bacterial pathogens and antibiotic sensitivity
      pattern.
AB  - All cases of septicemia among neonates admitted to the neonatal intensive care
      unit of the University of Ilorin Teaching Hospital, Ilorin, Nigeria between Jan
      1995 and Dec 1996 were studied. Our aims were (1) to assess the incidence and
      microbial epidemiology of neonatal sepsis, (2) to generate baseline data and
      necessary research question for a proposed study on predictors of neonatal sepsis
      in our centre. Microbiology records of patients with confirmed septicemia was
      reviewed. Each of these babies had a single venous blood sample from a peripheral
      vein taken under aseptic conditions and before commencement of antibiotics. The
      needed data were entered into a proforma. Of the 198 neonates screened for
      sepsis, there were 61 (30.8%) positive blood cultures. Twenty-nine (48%) of these
      were inborn. The total number of live births in the hospital during the study
      period was 4118, thus giving a hospital-based incidence of neonatal sepsis of
      7.04/1000 for in-born patients. The male:female ratio was 1.2:1. Overall
      Staphylococcus aureus was the commonest pathogen, accounting for 18 (29.5%) of
      the total isolates. Other pathogens were as follows; coagulase negative
      Saphylococcus albus 15 (24.6%), Klebsiella spp 10 (16.4%) and unclassified
      Coliforms 9 (14.8%). The predominant organisms in the first 48 hours were Gram
      negative bacilli; accounting for (70%) of the 10 isolates. Between 3 and 7 days
      of life the Gram positive cocci accounted for 12 (60%) of the 20 isolates while
      the Gram negative bacilli represented 40%. After 7 days, the predominant organism
      was Staphylococcus aureus (38.8%) while coagulase-negative Staphylococci were
      isolated in 7 of 31 isolates (22.6%). The sensitivity pattern showed that 94% of
      the organisms were sensitive to azythromicin, 77.8% to streptomycin, 73.3% to
      gentamicin and 69.2% to ampicillin-sulbactam. For the cephalosporins the isolates
      showed a sensitivity rate of 69% to ceftriaxone, 66.7% to ceftazidime and 58.3%
      to cefuroxime. As a group the Gram positive organisms had 100% sensitivity to
      Azythromcin, 85% to ampicillin-sulbactam, 63% to ceftazidime and 62.5% to
      gentamicin. In the Gram negative group, the best overall sensitivity was to
      ceftriaxone (86.4%). Gentamicin had 85.7% while sensitivity to ceftazidime was
      60%. The distribution of the organisms causing early and late onset sepsis were
      different. For early onset sepsis, the Gram negative bacilli as a group were the
      commonest organisms while Staphylococcus aureus was the commonest cause of late
      onset sepsis. There was a lower incidence of sepsis compared to reports from
      other parts of the country. This, in addition to differences in antibiotic
      sensitivity pattern call for more multi-centre studies on predictors of neonatal
      sepsis. The antibiotic sensitivity profiles suggest that the initial empirical
      choice of ampicillin-sulbactam and gentamicin appears to be the most rational for
      our environment.

PMID- 12518908
TI  - Trace element status and early physical growth of exclusively breastfed normal
      and asphyxiated Nigerian babies.
AB  - Serial anthropometry and assay of plasma iron (Fe), zinc (Zn) and copper (Cu)
      were done on 72 babies with birth asphyxia during the first six months of life to
      assess the pattern of their physical growth and trace element status,
      respectively. Eighty-seven non-asphyxiated babies served as controls. The mothers
      of babies in both groups also had their plasma assayed for Fe, Zn and Cu
      immediately following delivery. Asphyxiated babies were lighter than non
      asphyxiated controls during the first two months of life and they also had
      smaller mean occipito-frontal circumference at birth. While Fe, Zn and Cu status
      was generally comparable in both groups, the newborn Cu concentrations were very
      low compared with earlier reports. No baby showed any overt signs of trace
      element deficiency.

PMID- 12518909
TI  - Previous BFHI training and nurses' knowledge, attitudes and practices regarding
      exclusive breastfeeding.
AB  - The UNICEF/WHO Baby Friendly Hospital Initiative (BFHI) programme was developed
      to train health workers and equip them with the required knowledge and skills to
      protect, promote and support breastfeeding among mothers through the
      implementation of the "Ten Steps to Successful Breastfeeding". This study was
      conducted to assess the effect of BFHI training on knowledge, attitudes and
      support practices of nurses with regards to exclusive breastfeeding. A total of
      298 nurses in maternal and child health care units were interviewed, of these 113
      (37.1%) had participated in the BFHI training workshop. Significantly higher
      proportions of the BFHI trained nurses had the correct knowledge regarding the
      causes and management of common breastfeeding problems. The overall knowledge
      scores of the BFHI trained nurses was significantly higher than that of the
      untrained (11.9 +/- 1.8 versus 10.7 +/- 2.4 P < 0.01). Higher proportions of BFHI
      trained nurses reported correct support practices for the initiation and
      establishment of exclusive breastfeeding among mothers. The findings show that
      nurses who had participated in the BFHI training workshop were significantly more
      knowledgeable about some aspects of exclusive breastfeeding, they had more
      positive attitudes and were more likely to employ correct practices for the
      promotion of exclusive breastfeeding.

PMID- 12518910
TI  - A possible outbreak of Streptococcus pneumoniae invasive infection in children in
      Ibadan, Nigeria.
AB  - Streptococcus pneumoniae is an important aetiological agent of infections in
      children worldwide. The isolation rate of the bacteria has been strikingly low in
      the recent past in Nigeria. In a study of 1000 blood samples from patients, out
      of which 642 were from children in Ibadan between May 1999 and December 2000, 14
      isolates of Streptococcus pneumoniae were obtained (a prevalence rate of 1.4%).
      All the isolates were from children and clustered between 13th September and 22nd
      October 1999, period of 40 days and thereafter no more organisms were isolated.
      Antibiotic sensitivity testing of all isolates by disc diffusion method showed
      resistance to cotrimoxazole, tetracycline and penicillin to be 14%, 21% and 36%
      respectively. All the isolates were sensitive to chloramphenicol and
      erythromycin. No fatalities were recorded among the children. This may have
      indicated an outbreak and underscores the urgency for an epidemiological database
      in Nigeria to ascertain the exact clinical burden of S. pnemoniae infections so
      as to determine the appropriate vaccine strategies required for Nigerian
      children.

PMID- 12518911
TI  - Abdominal computed tomographic scan-merits and demerits over ultrasonography:
      evaluation of 70 cases.
AB  - Computed tomography (CT) and Ultrasonography (USS) are commonly used to ascertain
      the cause of abdominal symptoms. In a retrospective study of 70 Nigerian patients
      who had abdominal ultrasonography prior to abdominal CT scans, the most frequent
      clinical feature was abdominal pain, which was reported in 20.8% of the patients.
      The prevalent ultrasonographic finding was hepatomegaly (12.2%) while bowel
      displacement was the most frequently reported CT finding (18.3%). There was no
      correlation between USS and CT findings in 11 patients (15.7%). There was some
      agreement in the findings of both tests in 75.7% of cases. Additional findings
      were noted in 38 (54.3%) of the latter group of patients on CT scans. Hundred
      percent agreement was reported in both imaging techniques in 5 radiological
      findings namely: dilated gall bladder, renal cysts, ascites, adrenal mass and
      utero-cervical mass. These findings suggest a high yield of diagnostic accuracy
      from abdominal sonography and increased diagnostic details provided by CT
      imaging. Our overall impression is that the diagnostic information provided by
      the two techniques are complimentary.

PMID- 12518912
TI  - Diaphragmatic injuries.
AB  - This study seeks to define the clinical presentation, the usefulness of
      diagnostic tests, surgical management approach and outcome of treatment among
      patients with diaphragmatic injuries. One hundred and sixteen patients with
      diaphragmatic injuries were treated. This was 6.5% of 1,778 chest trauma
      patients. Eighty-four of these patients (6.8%) were among 1230 patients who had
      blunt chest injury and the remaining 32 patients (5.8%) were among 548 patients
      who had penetrating chest injury. The commonest mechanisms of injury were motor
      vehicle accidents (48.8%) for blunt and gunshot wounds (56.3%) for penetrating
      diaphragmatic injuries. The left diaphragm was most commonly involved (86.9% for
      blunt, 59.4% for penetration), 12.5% of the patients with penetrating chest
      injury had bilateral diaphragmatic injuries. There were no bilateral
      diaphragmatic injuries amongst the patients with blunt chest injury. Chest
      radiographs gave a highly positive yield in the diagnosis of blunt diaphragmatic
      hernias (67.9%) while nonspecific chest radiological findings (59.4%) were more
      common among those with penetrating injuries. In 57 patients (49.1%) out of 116,
      preoperative diagnosis of diaphragmatic hernia was certain. In the remaining 59
      patients (50.9%), diagnosis was intraoperative (40 patients), or at postmortem
      (19 patients). Surgery was emergent in 69 patients (71.1%), semi emergent in 21
      patients (21.6%) and elective in 7 patients (7.2%). Surgical approaches were
      mainly thoracotomy (57 patients), laparotomy (17 patients), laparotomy and
      thoracotomy (20 patients). In seventy seven patients (79.4%) the diaphragmatic
      injuries were left sided and in 20 patients (20.6%), the diaphragmatic injuries
      were right sided. There were 19 preoperative and 21 postoperative deaths. The
      overall mortality was 34.5%. Associated abdominal and thoracic injuries were the
      commonest causes of mortality among the patients with diaphragmatic injuries in
      this study. We conclude that diaphragmatic injury should be suspected in all
      thoracoabdominal trauma. Lack of specific signs and symptoms is common and a high
      index of suspicion is required. Routine chest radiograph remains the best
      screening test for diaphragmatic rupture. Diaphragmatic injury may be a predictor
      of severity of injury in blunt trauma patient. Surgical approach should be
      individualized.

PMID- 12518913
TI  - Trends in haemoglobin S, F, and A2 levels in West African and Caribbean sickle
      cell anaemia patients.
AB  - The levels of Haemoglobins S, F and A2, as well as Haemoglobin concentration,
      age, and average admissions per year (AVEADM) were compared in sickle cell
      anaemia patients of West African and Caribbean origins. Correlations of the
      haemoglobin levels with age, and the trends were also determined. The West
      African patients who comprised of 42 Nigerians, 23 Ghanaians and 13 Sierra
      Leoneans were compared to determine any differences in trend within them. One
      hundred and thirty-four patients, made up of 78 West Africans and 56 Caribbeans
      were analysed. The Caribbean patients were significantly older than the West
      African patients (P = 0.023). Haemoglobins S and F showed positive and negative
      significant correlations, respectively, with age in West African patients whereas
      there was no significant correlation in the Caribbean patients. Scatter charts
      and trendlines show that Haemoglobin S continued to increase while Haemoglobin F
      declined with age up to the age of 30 years in West Africans, Nigerians showing
      the steepest slope, while it remained stable with increasing age in the Caribbean
      patients. These findings may be due to the fact that the Caribbeans are genetic
      and socio-cultural mixtures of the different West African peoples, and the
      absence of indigenous malaria pressure.

PMID- 12518914
TI  - Family planning in rural Nigeria: a study among men.
AB  - Too few family planning studies in Nigeria have focused on the men. This
      community-based study determined the level of knowledge, attitude to and the
      practice of contraception among married men in a rural community in south west
      Nigeria. The study also identified socio-demographic and other variables
      associated with male contraceptive use. Knowledge was high for any family
      planning and any modern family planning method (90.9% and 73.3%). High level of
      knowledge alone was however not sufficient enough to promote a high level of use.
      The men's attitude was generally positive. Nearly half (47.3%) of respondents
      reported that they made family planning decisions with their spouses, though the
      larger majority thought it was the wife's responsibility to go for family
      planning. Among the men, 55.7% had ever used, while 26.7% were current users of
      any method. High level of formal education and duration of marriage (10 years and
      longer) were predictive of ever-used of a FP method while having fewer than 5
      surviving children negatively affected the use of FP methods. Current users of
      any family planning method were likely to be men with high formal education and
      with two or more surviving female children. The condom was the most utilized
      method but traditional methods of unproven efficacy, some of which were hitherto
      thought to be used only by women, were also widely used. Current use of
      contraceptives by males in this rural community is lower than what is generally
      reported for the country and the southwest region. It could be further improved
      when child survival is assured and when there is an improvement in the general
      level of education in the community.

PMID- 12518915
TI  - Refractive astigmatism and size of pterygium.
AB  - The study evaluates the relationship between varying sizes of pterygium and
      refractive astigmatism. All patients with pterygium seen at the eye clinic of the
      University College Hospital within a six months period were included. The length,
      width and area of pterygium were measured. Refractive astigmatism in the subjects
      were measured. The findings showed that the length of pterygium on the cornea has
      a statistically significant relationship with the amount of refractive
      astigmatism. The amount of astigmatism increases with increase in the length of
      pterygia. A linear regression analysis showed that 38% of the total variability
      in astigmatism could be explained by the length of pterygium. The width and area
      of pterygium on cornea had no significant association with amount of refractive
      astigmatism. Size of pterygia could be an important predictor of the amount of
      astigmatism in an eye. However, a larger study need to be done to find other
      possible factors associating refractive astigmatism in eyes with pterygium.

PMID- 12518916
TI  - Microbial isolates in chronic osteomyelitis--a guide to management.
AB  - Between August 1995 and December 1999, sixty patients with chronic osteomyelitis
      had the effluent from the discharging sinuses and bone biopsies cultured
      aerobically and anaerobically. 47 positive isolates were obtained and the
      organism commonly isolated both in the single- and two-organism isolates was
      Staphylococcus aureus. The sensitivity patterns of these isolates were carried
      out with the available antibiotic discs. 30 per cent of the organisms isolated
      were sensitive to ceftriaxone (Rocephine) and gentamycin.

PMID- 12518917
TI  - Seasonal accumulation of anthraquinones in leaves of cultivated Cassia podocarpa
      Guill et Perr.
AB  - Seasonal variations and spectrophotometric determination of anthraquinones in
      cultivated Cassia podocarpa are presented. The study shows that combined
      anthraquinones are concentrated in the leaves at peak flowering (2.43%) and
      lowest in the bark (0.21%). Anthraquinone glycosides reached peak levels during
      the months of October to March (dry season), the maximum being recorded during
      January to March. There was significant drop in glycosidic content during the
      period April to September (rainy season). There was slight increase in
      concentration of aglycones during the rainy season which may be due to inter
      conversion of some glycosides to the aglycones. However, the free aglycone
      content is much lower than the glycosides. This is desirable for optimum laxative
      activity and reduced toxicity. This study is significant because it provides
      useful information on the seasonal distribution of anthraquinones and the best
      period for harvesting leaves of C. podocarpa for drug development. The inclusion
      of C. podocarpa in the African Pharmacopoeia will, no doubt, enhance its
      commercialization as laxative and for its antimicrobial effect.

PMID- 12518918
TI  - Calciphylaxis: case report and literature review.
AB  - Tissue calcification is a well-recognized common metabolic disease, but
      calciphylaxis still remains an enigmatic rarity. The latter may be induced
      experimentally and acquired naturally in human diseases. Although many chronic
      azotemic or end stage renal disease patients (ESRD) with hyperparathyroidism
      (HPT) are at risk of calciphylaxis not all of them do develop the disease, even
      non-renal, patients may also develop this disease. Out of a total of about 2000
      hemodialysis, 15,000 dermatology and 26,000 medical patients seen over a three
      year period in a busy Saudi Arabian tertiary medical centre, we report a sentinel
      nephrology patient with sudden excruciatingly painful cutaneous calciphylaxis
      that necessitated acute dermatology emergency consultation, and present a review
      of the medical literature. In order to institute appropriate total quality
      management of this life-threatening, rare disease, it is advisable that a high
      index of suspicion should be entertained by dermatologists, general physicians,
      nephrologists, and pulmonologists in an appropriate clinical scenario.

PMID- 12518919
TI  - Issues and non-issues in hypertension in the Nigerian population.

PMID- 12518921
TI  - Trans-oral irrigation for the management of cervical esophagogastric anastomotic
      leak.
AB  - Over a period of 8 years, 15 of the 65 patients who had transhiatal esophagectomy
      (THE) for esophageal diseases and cervical esophagogastrostomy had cervical
      oesophagogastric anastomotic leak. Seven of the 18 patients (38.9%) with
      corrosive esophageal strictures (CES) due to acid burns had anastomotic leaks
      while 2 out of 6 patients (33.3%) and 6 out of 41 patients (14.6%) were the
      incidences of anastomotic leaks among alkali burnt and carcinoma of the
      esophagus. Anastomotic leaks were more commonly associated with surgery for CES.
      They were managed by trans-oral irrigation with water after ingestion of either
      soft/solid diet or high protein, high carbohydrate fluid diet along with adequate
      jejunostomy feeding. The age of the patients ranged between 5 to 65 years (mean
      38.8 +/- 15.7 year). Anastomotic leaks were diagnosed between 3rd to 10th
      postoperative day (mean 7.1 +/- 2.6 day). The period of transoral irrigation
      before closure of leakage ranged from 2 to 14 days (mean 6.1 +/- 2.9). In 12
      patients (80%) anastomotic leakage closed within 5 days, (mean 3.9 +/- 1.0). Two
      weeks after closure, all the patients had bouginage and every two weeks for
      another 3 dilation. Four of the 15 patients needed repeated two monthly dilation
      for 8 to 12 months. There were no other complications nor mortality in this
      study. There was psychological acceptance of this minimally invasive procedure.

PMID- 12518920
TI  - Effect of adrenaline on the glucose uptake by the canine hindlimb.
AB  - The effect of adrenaline on the glucose uptake by a non-exercising hindlimb was
      studied in fasted anaesthetized dog. Glucose uptake (mg/min) was calculated as
      the product of the venous blood flow and anterio-venous glucose difference (A -
      V). Although, adrenaline caused significant increase in venous blood flow, it
      however, reduced significantly the (A - V) glucose level and the glucose uptake
      by the hindlimb. The adrenaline effects were however, abolished by pretreating
      the animal with propranolol, a beta-adrenergic blocker. It was therefore
      concluded that the skeletal muscle of the canine hindlimb is not involved in
      glucose homeostasis during adrenaline hyperglycemia.

PMID- 12518922
TI  - Evaluation of the effectiveness of post-operative beta-irradiation in the
      management of pterygium.
AB  - A retrospective review of cases of pterygium excision using the bare sclera
      method followed by application of 2500-3500 rads of Sr 90 beta-radiation carried
      out between 1994 and the year 2000 at Ojulowo Eye clinic Ibadan and St Mary's
      Catholic Specialist Eye Hospital Ago-Iwoye, Nigeria. Follow up period was between
      six months and six years. A total of 124 eyes from 95 patients were operated. 58
      (61.1%) were males and 37 (38.9%) were females. The youngest patient was 10 years
      old while the oldest was 89 years mean 46.1 +/- 2 STD of 13.5. Most pterygia were
      unilateral and nasal in location. Improvement in visual acuity of between 2-6
      lines on snellen chart occurred in 6 (4.8%) of operated eyes. Recurrence
      necessitating repeat surgery and additional radiation occurred in 8 eyes (6.9%).
      The complications of surgery and beta radiation consisted of conjunctiva
      inflammation 10 (8.6%), cornea opacities 4 (3.2%), gritty sensation 3 (2.6),
      cataract 1 (0.8%). No case of sclera necroses was observed. Post-operative beta
      radiation is safe and effective in preventing recurrence of pterygium.

PMID- 12518923
TI  - Comparison of Siriraj Stroke Score and the WHO criteria in the clinical
      classification of stroke subtypes.
AB  - Clinical distinction between cerebral haemorrhage (CH) and cerebral infarction
      (CI) is important in the management of stroke patients in areas where CT scan
      facility is lacking or access limited by cost and distance. This distinction is
      necessary in our environment where an increasing proportion of patients are
      suspected to have haemorrhagic stroke. This study compares Siriraj stroke score
      (SSS) and the WHO criteria for the acute stroke syndrome as simple tools for this
      purpose. The computerised tomography (CT) brain scans of all patients referred
      with clinical diagnosis of stroke at the University College Hospital (UCH),
      Ibadan, and RADMED diagnostic centre. Lagos were retrieved and reviewed as well
      as the case notes of these patients at the referral hospitals. Relevant clinical
      data were extracted from the case records. The patients were classified into
      either CI or CH using the WHO criteria for acute stroke syndrome and the SSS.
      This classification was compared with the CT scan diagnosis using the latter as
      the gold standard. Data analysis was performed with Epi-info software, and Kappa
      statistics (k value) for comparability test with 95% confidence interval was used
      to compare the two clinical criteria with the gold standard. Ninety-six patients
      had complete clinical records and CT scan features consistent with the diagnosis
      of stroke, of which 52 were diagnosed as CI and 44 as CH. SSS had sensitivity of
      50% for haemorrhage and 58% for infarction with an overall accuracy of 54.2%. The
      WHO criteria for the acute stroke syndrome had sensitivity of 73% for haemorrhage
      and 69% for infarction with an overall accuracy of 71%. The kappa coefficient was
      0.18 for the SSS and 0.41 for the WHO criteria. The diagnostic accuracy of the
      WHO criteria for the acute stroke syndrome is higher than that of the Siriraj
      stroke score. The WHO criteria showed moderate agreement (k=0.41) with the CT
      scan, while the SSS showed no agreement (k=0.18). When CT scan is not affordable
      or its use is limited by distance, the WHO criteria for acute stroke syndrome
      could be more useful. A prospective study with a larger sample size is suggested
      for definitive conclusion.

PMID- 12518924
TI  - Sensorineural hearing loss in adults with sickle cell anaemia.
AB  - Sensorineural hearing loss (SNHL) is one of the known complications of sickle
      cell disease (SCD). However, there is paucity of information on SNHL as a
      complication of SCD, especially in sickle cell anaemia (SCA) in our environment,
      hence this study. This was a prospective study of pure tone audiological
      assessment of 167 adult SCA patients in stable condition attending the adult
      Sickle Cell Clinic and 100 apparently healthy Haemoglobin AA adults as control in
      the University College Hospital, Ibadan. Their ages ranged from 15 to 56 years
      for SCA and 15 to 65 years for the controls, with a mean age of 24.2 (+/- 8.2)
      and 28.7 (+/- 11.9) years respectively. There were 94 females (56.3%) and 73
      males (43.7%), fifty-two females (52%) and forty-eight males (48%), with a M:F
      ratio of 1:1.3 and 1:1.1 for SCA and controls respectively. Sensorineural hearing
      loss (SNHL) was observed in a total of 178 ears in 110 SCA patients and 68 ears
      in 47 controls with a prevalence of 66% and 47%, respectively. Sixty-eight
      patients (62%) and twenty-one controls (44.7%) had bilateral impairment, although
      only 18 SCA patients (11%) perceived hearing impairment. High frequency loss
      (4000-8000 Hz) was commonly affected in both the SCA patients and controls as
      compared to other frequency ranges. Low frequency range was involved in ten ears
      (9%) especially the right ear of some SCA patients. Decibel hearing level (dBHL)
      loss was in the mild range (26-40 dBHL) in 103 (58%) and 53 (78%) ears in the SCA
      and controls, respectively. Five patients had severe and profound dBHL loss. The
      range of dBHL loss was 26-43 dBHL especially in the high frequency range
      bilaterally for both the SCA and controls. Mean binaural hearing of 13 dBHL was
      recorded in both the SCA and controls for each octave frequency bilaterally in
      those with normal hearing while 26 and 23 dBHL were for those with impaired
      hearing respectively. Also, the mean dBHL for both ears was observed to be
      progressively worse with increasing age groupings, more especially in SCA
      patients. There was no significant correlation between the severity of hearing
      loss and the frequency of vaso-occlusive crisis. It is hoped that this study
      would have increased the awareness that SNHL is a common complication of SCA in
      our patients. There is thus the need for periodic evaluation of the auditory
      function of SCA patients in our environment.

PMID- 12518925
TI  - Pattern of active pulmonary tuberculosis in human immunodeficiency virus
      seropositive adult patients in University College Hospital, Ibadan, Nigeria.
AB  - Fifty-eight confirmed HIV-seropositive adult patients were studied. All subjects
      were interviewed and examined. Subjects with positive respiratory symptoms and
      signs had their sputum examined and cultured for Mycobacterium tuberculosis (M.
      tuberculosis). Their chest radiograph, full blood count (FBC) and erythrocyte
      sedimentation rate (ESR) were also estimated. Subjects with Pulmonary
      tuberculosis were treated using directly observed therapy short course (DOTS)
      regimen. Sixty-three percent of subjects were positive for Mycobacterium
      tuberculosis on direct smear and/or culture. Sputum acid fast bacilli (AFB)
      positive subjects who completed the intensive phase of antituberculous drugs were
      sputum converted at 2 months. The chest x-ray finding at diagnosis showed 2
      subjects (11%) with normal chest x-ray; localised lesion in 7 (37%) subjects;
      diffuse lesion in 7 (37%); pulmonary cavities in 3 (16%); miliary pattern in 2
      (11%); pleural effusion in 2 (11%); hilar adenopathy in 2 (11%). Repeat chest-x
      ray at 3 months showed complete clearance of pulmonary infiltrates in 29% whilst
      71% had appreciable improvement in radiologic features. The study showed that
      although chest x-ray may be "normal" in sputum AFB positive HIV infected
      individuals, radiologic picture tends to be more diffuse and extensive. This
      study was therefore undertaken to determine the pattern of PTB in HIV
      seropositive adult patients in U.C.H., Ibadan.

PMID- 12518926
TI  - Trabeculectomy in young Nigerian patients.
AB  - The results of 89 trabeculectomies performed on 56 patients under the age of 30
      years were reviewed. Data collected included age, sex, type of glaucoma, number
      of years of glaucoma before surgery, visual acuity, intraocular pressure,
      complications of surgery, presence of a filtering bleb and follow-up period.
      Complete success, denoted by a postoperative IOP of 21 mmHg or less without
      medical therapy, occurred in 50 eyes (56.2%). Qualified success, in which IOP was
      21 mmHg or less with additional medical therapy occurred in 31 eyes (34.9%) and
      failure, in which IOP was greater than 21 mmHg in spite of medical treatment
      occurred in 8 eyes (8.9%). Success was therefore achieved in 91.1% attaining an
      IOP of 21 mmHg or less, with or without additional medical therapy. The most
      statistically significant factor was age groups in which the highest success rate
      of 100% was achieved in the age group 20-29 years. The difference in the success
      rate across the age groups was statistically significant (x2 = 8.04, p = 0.01).
      Fornix based conjunctival flaps were also found to be associated with a
      statistically significant higher success rate (97.9%) as opposed to limbal based
      flaps (85.4%), x2 = 4.81, p = 0.03. Males in the study group had a significantly
      higher success rate (97%) than females (78.3%), x2 = 5.86, p = 0.011. A success
      rate of 100% was recorded in patients with developmental glaucoma, 86.1% in
      congenital glaucoma and 33.3% in secondary glaucoma. All the repeat
      trabeculectomies had congenital glaucoma. The presence of a bleb, although it had
      a higher success rate (93.4%) compared with the absence of a bleb (84.6%), was
      not statistically significant (x2 = 1.19, p = 0.27). Complications of surgery
      were mostly transient.

PMID- 12518928
TI  - Gunshot injuries in adults in the Abha region of Saudi Arabia.
AB  - In the four-year period from 1996 to 1999, 42 adult patients (age 12 years and
      above) were admitted to the Assir Central Hospital, Abha, Saudi Arabia, following
      gunshot injuries. The mean annual admissions for gunshot injuries was 10.5 +/-
      4.04 (range = 8-16 cases/annum). All the patients were males. The distribution of
      the patients' nationalities were: Saudis 66.7%, Yemenis 11.9%, Ethiopians 11.9%,
      Eritreans 7.1% and Sudanis 2.4%. In 38 cases, others shot the patient, while only
      one patient (2.4%) admitted to shooting himself accidentally. A pistol was used
      in 81% of cases while an air gun was used in 9.5% of the cases. Wound of entry
      analysis showed that gunshots were to the lower limbs in 20 cases (47.2%), the
      upper limbs in 22% and the chest in 13% of cases. Gunshots to the head and neck
      occurred in 7% and 2% of cases, respectively, while the abdomen was hit in 4% of
      cases. The injuries sustained included: superficial wounds (64.3%), haemothorax
      (9.5%), nerve injury (9.5%), lower limb fractures (9.5%), haematoma (7.1%), liver
      and kidney injuries (2.4%, respectively). Management included wound debridement
      and suturing (76.2%), thoracostomy tube drainage (14.3%), bullet removal (11.9%),
      internal fixation of fractures of long bones (9.5%), laparotomy and repair of gut
      (7.1%), nerve repair (4.8%), ulnar nerve graft (2.4%), and external fixation
      compound fracture of the tibia (2.4%). All the patients survived. The mean
      hospital stay was 15.45 +/- 23.06 days (range = 1-150 days). Although gunshot
      injuries are increasingly being reported from Saudi Arabia, the injuries are
      accidental and the morbidity appears to be low.

PMID- 12518927
TI  - Factors associated with oro-facial injuries among children in Al-Baha, Saudi
      Arabia.
AB  - This study was prompted by the dearth of injury data among children in Saudi
      Arabia. Data were collected prospectively on all children 0-15 years who
      presented to the King Fahad Hospital at Al Baha with oro-facial injuries over a
      period of five consecutive years. These records were analyzed for age, gender,
      seasonal distribution, cause, location and types of injuries. The mean age of the
      injured children was 6.2 +/- 3.7 years. Falls, motor vehicle accidents followed
      by direct blunt trauma were responsible for over 97 percent of all oro-facial
      injuries in children, and over 60 percent of all injuries were due to falls. The
      forehead, eye, periorbital areas and the mouth accounted for about two-thirds of
      all injury sites. Most injuries 356 (75.3%) occurred during the summer months
      while only 117 (24.7%) occurred during the winter months. The difference was
      significant (P<0.0001). The large majority of injuries, which occurred in
      children under the age of 6 years, took place at home, while road traffic
      accidents were the commonest cause of injury in the older children 6 years and
      above. Following logistic regression analysis, age (6 years and under) was
      associated with increased risk of injury while the winter months were associated
      with a lower risk. In addition, the study found no statistically significant
      difference in the prevalence by sex. Having a safe home environment, health
      education programmes directed towards the caretakers of young children and
      legislation in support of seat belts will go a long way towards reducing injuries
      among children in this community. A multi-disciplinary clinical management
      approach is envisaged due to the different injury sites and facilities would need
      to be equipped to take care of all types of oro-facial injuries.

PMID- 12518929
TI  - Beliefs and perceptions of ear, nose and throat-related conditions among
      residents of a traditional community in Ibadan, Nigeria.
AB  - ENT-related conditions constitute a major burden of disease in Nigeria. The bulk
      of the available studies on these conditions are derived from hospital-based
      studies that underestimate the extent of the problem. Few studies have explored
      the perceptions of community residents on the causes and treatment of these
      conditions. This article describes findings of a qualitative study that explored
      the perception of residents of Foko, a traditional community in Ibadan, Nigeria.
      Five traditional healers were interviewed in-depth while four focus group
      discussions were conducted for men and women to determine perception of types,
      causation and treatment modalities for ENT-related conditions. The healers
      mentioned seven ENT-related conditions including ear discharge, deafness,
      epistaxis, nasal catarrh, sore throat, neck swelling and hoarseness. Informants
      and discussants attributed mainly spiritual attack as the cause of many of these
      conditions. Many of the treatment remedies used are topical, including use of
      effirin leaf (Occimum gratissium) for nose bleeding and using cold red oil or
      honey to treat ear discharge. These procedures are dangerous and could aggravate
      the conditions. We discuss the implications of these findings for further
      research and clinical practice.

PMID- 12518930
TI  - Pattern of drug use in geriatric patients undergoing surgery under general
      anaesthesia.
AB  - Ninety-nine elderly patients aged between 65 and 84 years presenting for surgery
      have been studied as to their pattern of current drug use. Of these 47 (48%) were
      found to be on medication. Ten were on drugs prescribed by their physicians while
      37 (37.5%) were on self-prescribed drugs. The self-prescribed drugs used were
      analgesics 23%, haematinics 8%, anti-inflammatory agents 6%, benzodiazepines 4%,
      steroids 2%, and oral hypoglycaemic agent 1%. Apart from the analgesics, patients
      did not know the names of the drugs they were taking. The dangers in the use of
      self-prescribed drugs in anaesthesia are highlighted and a plea is made for
      persistent effort to elicit information of drug use among the elderly presenting
      for general anaesthesia in order to avoid drug interactions.

PMID- 12518931
TI  - Comparative effect of lisinopril and lacidipine on urinary albumin excretion in
      patients with type 11 diabetic nephropathy.
AB  - This study was carried out to assess whether with a similar degree of blood
      pressure reduction, Lisinopril compares favorably or otherwise with lacidipine in
      respect of effects on urinary albumin excretion and renal function as assessed by
      creatinine clearance, plasma creatinine, urea and electrolytes. Thirty
      hypertensive diabetic nephropathy patients with moderate hypertension were
      studied. After a 2-week washout period, they were allocated into two groups
      matched at baseline for age, sex, weight, blood pressure, and urinary albumin
      excretion rate as well as creatinine clearance. There were 8 males and 7 females
      in each group. One group received lisinopril (with furosemide if needed to
      control BP) and the other group received lacidipine. Staged increases in doses of
      antihypertensives were used until BP was controlled or maximum dose of 40 mg/day
      lisinopril or 8 mg/day lacidipine was reached. Furosemide was added to lisinopril
      if BP was not controlled at 40 mg/day. These medications were given for 12 weeks
      at the end of which measurements done at baseline were repeated. Comparison of
      baseline and end of study values of these parameters within the groups and
      between the two groups were made. Lisinopril group and lacidipine group achieved
      similar and highly significant reduction in blood pressure levels P < 0.001.
      There was reduction in urinary albumin excretion rate in both groups but this
      only reached statistical significance in the lisinopril group [480] [269] mg/day
      vs. 315 [202] mg/day P < 0.05] while for the lacidipine group it was not
      significant [491] [257] mg/day vs. 335 [182] mg/day P > 0.05]. However,
      comparison of albumin excretion rate between both groups at baseline and at end
      of the study did not show any significant difference, P > 0.1. With both drugs
      there is a tendency for creatinine clearance to increase and plasma creatinine to
      drop while plasma potassium tended to rise more with lisinopril than lacidipine
      but differences within and between both groups, did not reach statistical
      significance P > 0.05. In conclusion, blood pressure reduction was comparable in
      both drugs; both drugs reduced albuminuria but lisinopril appeared superior.
      Treatment with both drugs tended to increase creatinine clearance but both had no
      significant effects on blood sugar.

PMID- 12518932
TI  - Audit of emergency theatre utilisation.
AB  - This audit was undertaken to assess the utilisation of the emergency theatre in
      University College Hospital, Ibadan. It was also to find out if there was
      effective use of the emergency theatre space on a daily basis. Data was collected
      on all patients scheduled for emergency surgery excluding obstetric emergencies
      between May 1st and July 31st 1999. A total of 498 patients were booked for
      emergency surgery during the study duration and out of these, only 198 patients
      [38%] had their surgery performed. The number of patients booked per day ranged
      between 1 and 18 (Mean +/- S.D) [5.4 +/- 4.1], while the number operated ranged
      between zero and 9 (2.2 +/- 1.7). The General Surgery Unit had the highest number
      of cases booked (31.1%) and performed (38.9%). However, all the patients booked
      by the Gynaecological Unit (4.8% of total) were operated upon. Time interval
      between time of booking and the beginning of surgery ranged from 30 to 990
      minutes (431 +/- 296.7), while duration of surgery ranged from 25 to 750 minutes
      [121 +/- 96.5]. Theatre utilisation during this study was between 5 to 50% (mean
      26.9%) and the period of maximal utilisation was between 16.00 and 03.00 hours.
      Reasons why surgery was not performed on all (100%) booked patients included
      among others "Surgeons did not show up" (62%), "Surgery postponed by surgeons"
      (18%) and "Patient ill prepared for surgery" (10%). This study showed gross under
      utilisation of emergency theatre space with contributing factors mainly human and
      preventable.

PMID- 12518933
TI  - A seven-year audit of a diarrhoea training unit (DTU) in Port Harcourt, Nigeria.
AB  - The Diarrhoea Training Unit [DTU] of the University of Port Harcourt Teaching
      Hospital in Nigeria was established in 1991 and has, in addition to treating
      cases, been involved in training medical students, paediatric residents, health
      workers and mothers caregivers on correct case management of diarrhoeal disease.
      The accomplishment of the Unit over a defined time frame, January 1993 to
      December 1999, was evaluated by employing predetermined indicators and the data
      were analyzed by using the Statistical Package PEPI [Computer Programs for
      Epidemiologic Analysis Version 2.07a]. Eight thousand, four hundred and eighty
      six cases (4557 males and 3929 females) of acute diarrhoea were treated. Those
      with severe dehydration were eleven times fewer in 1998 and eight times fewer in
      1999 than in 1993. The number of Oral Rehydration Salts (ORS) sachets used in the
      Unit increased from 3064 in 1993/94 to 17,549 in 1998/99. There was no reduction
      in the number of cases treated, but the case-fatality rates dropped from 6 per
      1000 in 1993 to 0.6 per 1000 in 1999 [likelihood ratio chi2 = 9.874, p = 0.02].
      There was a significant reduction in the proportion of patients with bloody
      stools towards the end of the observation period [chi2(trend) = 82.60, 1 df, p =
      0.000 (1.00E-19)]. These results indicate some positive impact on the severity of
      diarrhoea in the area, but preventive measures should now constitute the main
      thrust.

PMID- 12518934
TI  - Ectopic chest tube insertions: diagnosis and strategies for prevention.
AB  - In the six-month period from October 1999 to March 2000, the authors carried out
      a prospective study of ectopic chest tube placements (ECTP) diagnosed at the
      Assir Central Hospital, Abha, Saudi Arabia. During the reference period, 63 chest
      tube placements were carried out in 44 patients while one patient was from a
      medium-sized general hospital within a neighbouring city. The grades of the
      surgeons who had performed the ECTP were: surgeon specialists based at peripheral
      hospitals--5 (83.3%), and surgical resident in training at the regional referral
      centre--1 (16.7%). Mean age = 29.7 years; M:F ratio = 2:1. A total of 6 cases of
      ECTP were found constituting 9.5% of all chest tube insertions mostly from small
      hospitals situated in the peripheral, non-urban areas. The diagnosis of ECTP was
      made on plain chest radiographs in 3 patients (50%) and on the CT scans of the
      chest in 3 patients (50%). The ECTP was into the lung (2 cases--33.3%),
      subdiaphragmatic. intraabdominal (3 cases--50%), and chest wall, subcutaneous (1
      case--16.7%). Misdiagnosis and failure to carry out a finger exploration of the
      pleural cavity prior to the placement of the chest tube rather than the use of
      chest tubes with trocars was to blame. The incidence of ECTP (9.5%) is high and
      underlines the need for proper training in the methodology of chest tube
      insertion for junior surgical cadre.

PMID- 12518935
TI  - Dentofacial findings in Down's syndrome: report of case.
AB  - Provision of dental services to the mentally subnormal in our society is
      relatively neglected. A patient with Down's syndrome who sought dental treatment
      is reported. Following the assessment of the patient, he needed orthodontic
      surgical treatment and scaling and polishing. The former was not given due to the
      cost, complications and stress of such an involving procedure vis-a-vis the
      benefit to such a patient. However, patient received thorough scaling and
      polishing with emphasis on routine 6-monthly dental check-ups given. Handicapped
      individuals are beginning to seek dental services and the percentage of them
      doing so is likely to increase as more of such individuals are now staying in the
      normal home setting. Early preventive treatments for such patients are
      encouraged. Therefore, the dentists and the rest of the therapy team should be
      sensitized to face the challenge of providing services to them.

PMID- 12518936
TI  - Rapidly progressive glomerulonephritis in adult Nigerians: a report of 4 cases.
AB  - The clinicopathological features of rapidly progressive glomerulonephritis (RPGN)
      were studied in 4 young adult Nigerians who presented with acute GN. There was a
      predilection for males with a male to female ratio of 3:1. Hypertension.
      nephrotic-range albuminuria, haematuria granular and cellular urinary casts, and
      a rapid progression to severe renal failure or death were the findings in all
      four patients. Renal biopsy revealed histological features compatible with
      findings in RPGN in all the patients, including the presence of crescents and
      epithelial cellular proliferation. The study shows that the early development of
      hypertension and deterioration of renal function in patients with features of
      acute glomerulonephritis should arouse suspicion of a rapidly progressive GN
      whose course could be altered by appropriate therapeutic measures, some of which
      are highlighted.

PMID- 12518938
TI  - Popliteal artery pseudoaneurysm in a child due to gunshot injury.
AB  - This is a case of a 12-year old boy who sustained gunshot injury to his left knee
      region. After initial debridement and closure of his wounds, the patient
      presented seven weeks later with a large pulsatile swelling of his lower thigh
      and painful flexion deformity of his knee. Angiography revealed large
      pseudoaneurysm of the popliteal artery and arteriovenous communication. The
      patient underwent successful repair of his popliteal artery with autologous long
      saphenous vein graft. The initial diagnostic difficulty in these cases, the
      different types of injury and the therapeutic modalities of similar cases in the
      literature are discussed.

PMID- 12518937
TI  - Acute isovolaemic haemodilution in two Jehovah's Witnesses presenting for major
      intracranial surgery.
AB  - The Jehovah's Witnesses (JWS) is a religious sect with strong convictions against
      acceptance of blood and its products for medical care, including surgery. We
      present two cases of JWS, aged 24 and 19 years old, who had craniectomy for
      trauma and craniotomy for tumour excision, respectively. A team approach was
      employed in the care of both patients. During exhaustive preoperative discussions
      they re-affirmed their religious convictions but agreed to some modifications.
      Both patients accepted Acute Isovolaemic Haemodilution (AIH). However one of them
      insisted on non-discontinuation of the line used in collecting the blood from the
      vein, as that would constitute blood storage. The preoperative Packed Cell Volume
      (PCV) was 45% and 41% for the trauma and the tumour patients respectively. Two
      units of blood (1000 ml) were collected from each patient resulting in post
      donation PCV of 40% and 33%. The intraoperative blood loss was 300 ml and 2000
      ml, respectively, and the units and crystalloid fluids were transfused for
      replacement. Postoperative PCV were 42% and 25%. The latter improved to 30% over
      the following two weeks with oral haematinics. The two cases are discussed in the
      light of the experience gained.

PMID- 12518939
TI  - Axillary artery injury: report of two cases and review of the literature.
AB  - These are the cases of two young men, 21- and 28-year old, who sustained
      penetrating stab injuries to their axillary arteries. Both patients presented
      initially with profuse bleeding and were in a state of shock. The first patient
      underwent initial emergency surgery to control his bleeding whereby deep stitches
      were inserted around the axillary vessels and nerves and ended up with permanent
      iatrogenic Median nerve palsy. The bleeding in the second patient was controlled
      initially by compression dressing and he underwent successful vascular repair of
      the axillary artery with full recovery of his upper limb function. In this paper,
      we are discussing the initial management problem of these cases and the results
      of similar injuries and their repair in the literature.

PMID- 12518940
TI  - Evidence-based orthodontics.

PMID- 12518941
TI  - Orthodontic biomaterials: from the past to the present.

PMID- 12518942
TI  - Three-dimensional cephalometry using helical computer tomography: measurement
      error caused by head inclination.
AB  - We performed a study of three-dimensional (3-D) linear measurements in the
      maxillofacial region using helical computer tomography (CT). The high accuracy of
      the linear measurements showed errors of less than 5% from the actual measures.
      But, it is possible that the accuracy was influenced by inaccurate head
      positions. In this study, we evaluated the errors when the head positions were
      tilted using the 3-D measurement system. Helical CT was used to scan a dry skull,
      and the data were reconstructed into a 3-D image. A total of 18 points were
      plotted on the 3-D images, and the distance between two points was calculated
      when the points were expressed as coordinates. A dry skull was tilted by 10
      degrees from the reference position in the horizontal, sagittal, and frontal
      planes and was then tilted in a combination of directions. Scanning was performed
      with slice thicknesses of 1 mm, 3 mm, 5 mm, and 7 mm. The length between two
      points measured by 3-D cephalometry was compared with the actual length
      determined using an antenna meter and a caliper and expressed as percentage
      errors of the actual length. In all head positions, errors in all linear
      measurements on the images and the actual length measured on the skull were less
      than 5% when a slice thickness of 1 mm or 3 mm was used. But, on using a slice
      thickness of 5 mm or 7 mm, some linear measurements showed larger measurement
      errors. Therefore, a thickness of less than 3 mm was thought to be clinically
      appropriate because the accuracy of the measurements was not influenced by head
      rotation.

PMID- 12518943
TI  - Longitudinal investigation of soft palate and nasopharyngeal airway relations in
      different rotation types.
AB  - The relationship between the soft palate and the nasopharyngeal airway in
      different mandibular growth rotation models was investigated. A total of 72
      lateral cephalograms were obtained three years longitudinally from 24
      individuals. The subjects had a mean age of 10.7 +/- 1.2 years and showed a
      normal (n = 8), posterior (n = 8), and anterior (n = 8) mandibular rotation
      pattern. Linear and angular measurements of the soft palate and nasopharyngeal
      airway were recorded by using PORDIOS computer program and were examined by means
      of descriptive statistics and paired t-tests. A linear increase in the soft
      palate length (SPL) was observed in all groups, with the posterior mandibular
      rotation group showing the largest increase within the observation period (28.56
      +/- 4.83 to 34.98 +/- 2.87; P < .01). According to the paired t-test, palatal
      plane (ANS-PNS)/soft palate tip (SPT) angle showed a statistically significant
      decrease in the posterior rotation group (P < .01). The ratio between SPL and
      superior nasopharyngeal space (SPS) did not show a statistically significant
      difference among the groups. Although various amounts of soft palate and
      nasopharyngeal airway growth occurred in the different mandibular rotation types,
      the ratio between SPL and SPS (SPL/SPS), which plays an indispensable role in
      velopharyngeal functions, did not show a statistically significant difference in
      the groups. This assured velopharyngeal closure throughout the active growth
      period.

PMID- 12518944
TI  - Temporomandibular joint effects of activator treatment: a prospective
      longitudinal magnetic resonance imaging and clinical study.
AB  - The aim of this prospective longitudinal clinical and magnetic resonance imaging
      (MRI) study was to analyze the effect of Activator treatment on the disc-condyle
      complex and the posterior attachment of the temporomandibular joint (TMJ)
      considering the degree of compliance in the evaluation. The material was
      comprised of 30 class II, division I patients (nine girls and 21 boys) who
      underwent Activator treatment. The average pretreatment age of the subjects was
      11.4 years. Parasagittal MRIs in closed mouth position from before and after one
      year of Activator treatment were analyzed metrically. Possible clinical and
      subclinical soft tissue lesions of the posterior attachment of the TMJ were
      assessed by passive joint loading before, after six months, and after one year of
      Activator treatment. The overjet was continuously documented as a clinical
      measure for treatment reaction. To assess patient compliance, the subjects had to
      perform daily wearing-time records. Furthermore, the Activator was clinically
      inspected for fitting accuracy and signs of wear. The results revealed the
      following: (1) during the one-year treatment period the sagittal dental arch
      relationship improved, but a class I occlusion could not be achieved in all
      patients; (2) on average, a physiologic position of disc, condyle, and fossa was
      present both before and after one year of Activator treatment; (3) a pretreatment
      physiologic disc-condyle relationship was unaffected by Activator therapy; 4) a
      pretreatment disc displacement could not be repositioned during Activator
      treatment; (5) the prevalence of a subclinical capsulitis of the inferior stratum
      of the posterior attachment increased during Activator treatment; and (6) the
      degree of compliance had no influence on the disc-condyle relationship or the
      reaction of the posterior attachment of the TMJ.

PMID- 12518945
TI  - Comparison of skeletal and dental morphology in asymptomatic volunteers and
      symptomatic patients with bilateral disk displacement with reduction.
AB  - The purpose of this study was to evaluate the effect of bilateral disk
      displacement with reduction (BDDR) on the skeletal and dental pattern of affected
      individuals. There were 42 symptomatic female patients and 46 asymptomatic normal
      female volunteers. All study participants had bilateral high-resolution magnetic
      resonance scans in the sagittal (closed and open) and coronal (closed) planes for
      evaluation of the temporomandibular joints. Linear and angular cephalometric
      measurements were taken to evaluate the skeletal, denture base, and dental
      characteristics of the two groups. Analysis of variance was used to compare the
      symptomatic subjects with the control subjects. The length of both the anterior
      (S-Na) and posterior (S-Ba) cranial base was smaller in the BDDR group. SNA and
      SNB angles were also smaller in the symptomatic group. There were also
      significant differences in the denture pattern. The interincisal angle was larger
      and the upper incisor was more retroclined in the BDDR group. This study showed
      that alterations in skeletal morphology may be associated with disk displacement
      (DD). The mechanisms by which DD is produced or the mechanisms that cause that
      skeletal alteration are yet to be clarified. This study suggests that subjects
      with BDDR may manifest altered craniofacial morphology. The clinician should be
      aware of this possibility especially for the growing patients and the
      orthognathic surgery candidates.

PMID- 12518946
TI  - Effects of mandibular position and body posture on nasal patency in normal awake
      subjects.
AB  - The purpose of this study was to examine the changes in nasal patency induced by
      forward mandibular displacement or changes in body posture. Fifteen healthy
      adults participated in this study. To examine the influence of mandibular
      position, nasal resistance was recorded in intercuspal, middle, and maximum
      forward positions. To evaluate the effect of body posture, nasal resistance was
      recorded in the four postures of sitting erect, 30 degrees and 60 degrees
      dorsally reclined, and supine. The nasal patencies recorded in the middle and
      maximum forward mandibular positions were significantly higher than those
      recorded in the intercuspal position. Regarding the effect of body posture, the
      nasal patency showed a progressive decrease from the sitting erect position to
      the supine position. These results suggest that changes in mandibular position
      and body posture significantly affect nasal patency and that mandibular position
      and body posture should be considered basic information in the treatment of
      obstructive sleep apnea.

PMID- 12518947
TI  - The effect of saliva contamination on shear bond strength of orthodontic brackets
      when using a self-etch primer.
AB  - The purpose of this study was to assess the effect of saliva contamination on the
      shear bond strength of orthodontic brackets, at various stages of the bonding
      procedure using a new self-etch primer. Brackets were bonded to 52 extracted
      human molars according to one of the following four protocols. Group I
      (uncontaminated control): A self-etch acidic primer, Angel I (3M/ESPE
      Minneapolis, Minn) was placed on the enamel for 15 seconds, gently dried with
      air, and light cured for 10 seconds. Precoated brackets APC II (3M Unitek,
      Monrovia, Calif) were then placed on the teeth and light cured for 20 seconds.
      Group II: The enamel surface was first contaminated with human saliva for 10
      seconds, blown off with an air syringe for five seconds. The bonding procedure
      was then repeated as in group I. Group III: The self-etch primer was applied for
      15 seconds, gently dried with air, and light cured for 10 seconds. The surface
      was then contaminated with human saliva for 10 seconds, blown off with an air
      syringe for five seconds. The precoated brackets were then bonded as in groups I
      and II. Group IV: The enamel surface was contaminated with human saliva for 10
      seconds, blown off with an air syringe for five seconds. The self-etch primer was
      applied. The surface was then re-contaminated with human saliva for 10 seconds,
      blown off with an air-syringe for five seconds. The precoated brackets were then
      bonded as in groups I, II, and III. The results of the analysis of variance (F =
      4.79) indicated that the shear bond strengths of the four groups were
      significantly different (P = .005). Tukey HSD tests indicated that contamination
      both before and after the application of the acid-etch primer resulted in a
      significantly lower (=1.7+/-1.4 MPa) shear bond strength than either the control
      group (=6.0+/-3.5 MPa) or the groups where contamination occurred either before
      (=4.8+/-3.3 MPa) or after (=4.8+/-3.3 MPa) the application of the primer. The new
      acid-etch primer can maintain adequate shear bond strength if contamination
      occurs either before or after the application of the primer. On the other hand,
      contamination both before and after the application of the primer significantly
      reduced the shear bond strength of orthodontic brackets.

PMID- 12518948
TI  - Effect of using self-etching primer for bonding orthodontic brackets.
AB  - Questions over the use of self-etching primers with composite resin adhesives in
      the bonding of orthodontic brackets remain unsolved. In addition, there are no
      previous reports on the efficacy of self-etching primers with resin-modified
      glass ionomer cements for bonding orthodontic brackets in orthodontic dentistry.
      The purpose of this study was to determine the shear bond strengths of
      orthodontic brackets bonded with one of four protocols: (1) a composite resin
      adhesive used with 40% phosphoric acid, (2) the same composite resin used with
      Megabond self-etching primer, (3) a resin-modified glass ionomer cement adhesive
      used with 10% polyacrylic acid enamel conditioner, and (4) the same resin
      modified glass ionomer cement used with Megabond self-etching primer. The
      appearance of the tooth surfaces after acid etching or priming was observed with
      a field-emission scanning electron microscope (FE-SEM). When used with resin
      modified glass ionomer cement, Megabond self-etching primer gave no significantly
      different shear bond strength compared with polyacrylic acid etching. But when
      used with composite resin adhesive, Megabond self-etching primer gave
      significantly lower shear bond strength than phosphoric acid etching. However,
      the shear bond strength of orthodontic brackets bonded with composite resin
      adhesive after Megabond priming was almost the same as that of brackets bonded
      with resin-modified glass ionomer cement after polyacrylic acid etching. FE-SEM
      observation revealed that Megabond self-etching primer produced less dissolution
      of enamel surface than did phosphoric acid and polyacrylic acid etching. Megabond
      self-etching primer may be a candidate for bonding orthodontic brackets using the
      resin-modified glass ionomer cement for minimizing the amount of enamel loss.

PMID- 12518949
TI  - Subjective need and orthodontic treatment experience in a Middle East country
      providing free orthodontic services: a questionnaire survey.
AB  - The aims of this study were to explore orthodontic treatment experience,
      subjective need for treatment, and perceptions of teeth and dental appearance in
      relation to background factors such as funding system, area of living, age,
      gender, ethnicity, and socioeconomic status. The subjects were 1076 randomly
      selected second-year high school students from a rural (Jahra) and an urban
      (Capital) area of Kuwait, with a mean age of 15.1 years. Kuwaiti citizens
      constituted 79% of the sample, and the rest were of other Arab origins. The data
      were collected using a questionnaire. Orthodontic treatment rate was
      significantly higher for Kuwaitis (10%) than for non-Kuwaitis (2%). Among Kuwaiti
      subjects, urban area of living and female gender increased the odds of receiving
      orthodontic treatment. Subjective treatment need was 36%, with no difference
      between Kuwaiti and non-Kuwaiti subjects, but Kuwaitis in the rural area
      expressed subjective treatment need less often than those in the urban area. The
      results suggest that access to free-of-cost orthodontic treatment was likely to
      affect treatment rate, whereas it did not seem to influence the self-perceived
      need for treatment. Gender and area of living may be significant for the
      distribution of free-of-cost orthodontic treatment.

PMID- 12518950
TI  - National Institute of Dental and Craniofacial Research efficacy trials of
      bionator class II treatment: a review.
AB  - Reviewing publications from two North American functional appliance efficacy
      trials on Class II/1 malocclusions, we conclude that preadolescents show first
      molar correction in 13% of untreated cases, 38% of bionator-treated cases, and
      50% of combined headgear/biteplane-treated cases. Also, bionator and headgear
      reduce ANB differences at nearly equivalent rates (degrees/year). Thirty-two
      percent of untreated patients show favorable reductions (>0.5 degrees/y),
      compared with 80% of patients treated by either bionators or headgear. Successful
      outcomes, however, are highly dependent on the severity of the malocclusion.
      Using either headgear or bionators, clinicians should expect successful Class II
      molar correction in over 57% of preadolescents presenting with half cusp molar
      discrepancies. When left untreated, 30% of such patients are reported to attain a
      Class 1 molar relation. But only 5% of cases presenting with greater than half
      cusp discrepancies are found to resolve themselves. The bionator appliance,
      though, corrects 30% of such cases, and combined headgear/biteplane treatment
      corrects 40%.

PMID- 12518951
TI  - Detection of an early ossification of thyroid cartilage in an adolescent on a
      lateral cephalometric radiograph.
AB  - We report ossification of the thyroid cartilage detected on a routine lateral
      cephalometric film and discuss the clinical implications of this finding. The
      thyroid cartilage is a part of the laryngeal cartilaginous complex and may
      undergo calcification or endochondral ossification (or both), thereby becoming
      visible radiographically. Usually, ossification is visible only in individuals
      over the age of 20 years. It is unusual to see ossification in children or
      adolescents. We report here a case of thyroid ossification in a 14-year-old
      patient that is visible on a routine lateral cephalometric radiograph. An
      incidental limbus vertebra is also noticed situated anteroinferior to the fourth
      cervical vertebra.

PMID- 12518952
TI  - Cephalometric and in vivo measurements of maxillomandibular anteroposterior
      discrepancies: a preliminary regression study.
AB  - One of the aims of the present investigation was to assess three-dimensionally
      the anteroposterior discrepancy of dental bases using a noninvasive direct
      procedure. A second aim was to verify the relationship of three-dimensional soft
      tissue measurement to the well-established two-dimensional cephalometric
      assessments of anteroposterior discrepancy. Dental and facial landmarks were
      directly digitized on 20 orthodontic and maxillofacial surgery patients aged 8 to
      26 years using an electromagnetic three-dimensional computerized digitizer. The
      anteroposterior maxillomandibular discrepancy was measured by calculating the
      linear distances between the projections of subnasal and sublabial landmarks on
      the occlusal plane, subnasal and sublabial landmarks on Camper's plane, and
      insertion of maxillary and mandibular median labial frenula on the occlusal
      plane. From lateral cephalograms of the same patients, the following measurements
      were obtained: subspinale point-nasion-supramentale point (ANB) angle; corrected
      ANB angle that compensates for the position of the maxilla and rotation of the
      mandible relative to the cranial base; Wits appraisal; MM-Wits, linear distance
      between the projections of points A and B on the bisector of the palatal plane to
      mandibular plane angle; and soft-tissue Wits, linear distance between the
      projections of soft-tissue points A and B on the bisecting occlusal plane. The
      best two-dimensional vs three-dimensional linear regression (r = 0.91) was found
      between Wits appraisal and the linear distances between the projections of
      maxillary and mandibular median labial frenula on the occlusal plane (Wits = 
      1.05 x 3D measurement - 3.75). The three-dimensional evaluation of the sagittal
      discrepancy of the jaws directly performed in vivo may allow a more complete
      analysis of a patient's soft-tissue drape together with the underlying hard
      tissue structure.

PMID- 12518953
TI  - Optimization of unilateral overjet management: three-dimensional analysis by the
      finite element method.
AB  - The main goal of this research was to introduce, evaluate, and mathematically
      optimize the treatment procedure of unilateral overjet cases. Patients with Class
      II subdivision malocclusions usually reach a point with canines in a Class I
      position, and a unilateral overjet remains to be treated at the next stage of
      treatment. This study tried to prepare an archwire design that combines the
      midline-shift correction and the unilateral overjet reduction simultaneously. The
      analyses of displacements were carried out by the finite element method. The
      upper dental arch was designed three-dimensionally. Three archwire designs that
      were thought to be useful in these cases were modeled and engaged the dental-arch
      model separately. Three-dimensional displacements of the mesio- and
      distoincisolabial point angles of each incisor were assessed. Shortcomings of
      each design concerning the main treatment objectives were eliminated by
      optimization. Modeling and optimization of wire ligation methods were the last
      phase of this study. The use of an archwire containing a closed vertical loop
      with a helix distal to the lateral incisor on the affected (excess overjet) side
      and an open vertical loop without a helix distal to the lateral incisor on the
      normal side (normal overjet) while lacing the four incisors can be suggested as
      an optimum procedure to treat a unilateral overjet that is combined with a
      midline shift. The archwire cross-section depends on the initial position of the
      incisors. This mechanotherapy can be prescribed for both dental arches.

PMID- 12518955
TI  - Dialysis in acute renal failure: is more better?
AB  - An increasing body of evidence indicates therapy dose and intensity influence the
      outcome of dialyzed ARF patients. However, a number of unanswered questions
      remain on this issue. These questions need to be addressed in future prospective,
      controlled trials that assess the effect of dose and intensity on outcome both
      within and between the various ARF renal replacement therapies, with appropriate
      and clinically relevant control arms. Such investigations should provide
      guidelines ultimately for the dialytic management of critically ill patients with
      ARF.

PMID- 12518954
TI  - Stress distribution produced by the correction of the mandibular second molar in
      lingual crossbite.
AB  - The purpose of this study was to evaluate the stress distribution produced in the
      dentoalveolar system by a mandibular posterior crossbite appliance used for the
      correction of mandibular second molars in lingual version. A photoelastic model
      was fabricated using a photoelastic material (PL-3) to simulate alvelolar bone
      and ivory-colored resin teeth. The model was observed anteriorly and posteriorly
      with a circular polariscope and photographically recorded before and after
      activation of mandibular posterior crossbite appliances. An uncontrolled tipping
      and an extrusive force were generated when the traction force was applied on the
      buccal surface of the mandibular second molar. A controlled tipping and an
      intrusive force were generated when the traction force was applied on the lingual
      surface of the mandibular second molar. We concluded that to escape the extrusion
      and uncontrolled tipping that creates occlusal interferences associated with the
      correction of mandibular second molars in lingual version, the lingual traction
      force is more useful than the buccal traction force.

PMID- 12518956
TI  - Peripheral vascular disease in end-stage renal disease patients.

PMID- 12518957
TI  - Platelet activation and PDGF-AB release during dialysis.
AB  - During hemodialysis the blood-membrane contact causes a release of platelet
      granule content, which contains Platelet Derived Growth Factor (PDGF-AB). In view
      of its possible role in accelerated atherosclerotic processes, we evaluated the
      intra- and post-dialytic changes in PDGF-AB serum levels during hemodialysis
      sessions performed with Hemophan and Polysulfone membranes. PDGF-AB, PF4, betaTG
      and MPV levels were determined in the peripheral blood in 30 patients each of
      whom underwent 6 dialysis sessions: 3 with Hemophan (HE) membrane and 3 with
      Polysulfone (PS) membrane, interpolated by a wash out session with PS membrane.
      Blood samples were taken at times 0', 30', 120', 180', 240' during dialysis
      sessions and at 1, 4 and 20 hours after the end of the session. Statistical
      analysis was done using the ANOVA one way test and Student's t test PDGF-AB serum
      levels initially increased and, except for a sharp fall at 120', remained
      constantly high during HD with both membranes tested, not returning to basal
      values until 20 hours after the end of the session. PF4, betaTG and MPV all
      showed a similar trend to PDGF. No statistically significant difference was found
      between the two membranes tested. PDGF-AB, a powerful growth factor in cells of
      mesenchymal origin, is released during dialysis mainly as a result of the blood
      membrane contact. This we found regardless of the type of dialyzer we tested,
      and, above all, proved to return very slowly to basal values. We speculate that
      the release of PDGF-AB could play a part like other atherosclerosis risk-factors
      in the appearance and worsening of atherosclerotic lesions in hemodialysis
      patients.

PMID- 12518959
TI  - Model study of blood flow through a stent in the aorto-iliac bifurcation.
AB  - Atherosclerotic ailments play a major role in industrial societies.
      Atherosclerotic disease causes stenotic narrowing of the arterial vessel system.
      These narrow passages can be widened with balloon angioplasty and stents are
      introduced to keep the passage open. In this study, stents designed for the aorto
      iliac bifurcation are considered. Most of these stents used in peripheral
      arteries are self-expanding stents made from Nitinol, a thermo-reactive alloy.
      The insertion is done under radiographic control. However, the delicate metallic
      structure of the stent usually casts only a weak radiographic shadow and thus is
      difficult to detect. A stent with an innovative radio opaque tantalum marker
      (Luminexx, C.R. BARD--Angiomed, Karlsruhe), overcomes this problem. However, the
      markers extend into the blood flow and the question arises whether the markers
      may cause the generation of thrombi. In a model study in an enlarged model of the
      aorto-iliac bifurcation with an inserted stent the flow was visualized. The
      enlarged scale permits the observation and video recording of the flow in great
      detail. The Reynolds similarity is kept. A subsequent analysis of the flow in the
      vicinity of the markers shows a short residence time. These results indicate that
      the additional markers do not increase the risk of thrombus generation.

PMID- 12518958
TI  - Recovery of rats with fulminant hepatic failure by using a hybrid artificial
      liver support system with polyurethane foam/rat hepatocyte spheroids.
AB  - We studied the recovery of rats with fulminant hepatic failure (FHF) by treating
      them with our original hybrid artificial liver support system (HALSS). FHF was
      induced by a two-thirds partial hepatectomy and 10 minutes of hepatic ischemia.
      Rats with FHF were treated with a polyurethane foam/spheroid HALSS including 2.0
      x 10(8) hepatocytes for 1 hour (HALSS group, n = 5), and with the same system
      without hepatocytes in the artificial liver module as a control experiment (sham
      HALSS group, n = 3). The level of blood constituents, ammonia, glucose and
      creatinine, showed no major difference between the two groups at the end of
      treatment. All rats in the sham-HALSS group died within 5 hours after treatment.
      However, the level of blood constituents of rats with FHF in the HALSS group
      improved with time, and all rats in the HALSS group recovered. Liver tissue of
      rats treated with HALSS showed cell mitosis and improvement from injury. These
      results indicated that our HALSS has a strong possibility to induce recovery from
      hepatic failure.

PMID- 12518960
TI  - Heart rate effect on hemodynamics during mechanical assistance by the intra
      aortic balloon pump.
AB  - Heart rate (HR) has been characterized as an important cardiovascular parameter
      that affects acute hemodynamic performance of intra-aortic balloon
      counterpulsation (IABC). However, the effect of HR on hemodynamics during
      mechanical assistance by the IABC has neither been clarified nor quantified. We
      sought to evaluate the relationship between IABC and HR and also to examine
      whether there is a range of HR with optimum hemodynamic response to IABC.
      METHODS: 20 patients (14 males--6 females, mean age 64.4 +/- 11.4 years) with
      post-infarction cardiogenic shock undergoing IABC treatment were evaluated.
      Hemodynamics were recorded for each patient once per day during the assistance
      period; 131 measurements were taken and thus a wide range of heart rates was
      obtained (64-141 bpm). The following changes in aortic pressures were used to
      evaluate acute IABC performance on: a) the maximal increase of diastolic aortic
      pressure induced by IABC and b) the reduction in systolic and end-diastolic
      aortic pressure. RESULTS: Non-linear regression analysis and analysis of variance
      revealed that a significant correlation exists between IABC performance indices
      and heart rate. At HR<80 bpm, IABC performance tended to be reduced, whereas the
      increase in HR above 110 bpm resulted in a significant reduction of all IABC
      performance indices. In contrast, IABC operating at 80-110 bpm resulted in
      optimum hemodynamic performance. In conclusion, the effect of heart rate on IABC
      performance is non-linear indicating that IABC may be more effective when
      operating within 80-110 bpm.

PMID- 12518961
TI  - Polymerized degradable hyaluronan--a platform for stent coating with inherent
      inhibitory effects on neointimal formation in a porcine coronary model.
AB  - Biodegradable hyaluronan (hyaluronic acid, HA) made insoluble by self-cross
      linking in the presence of N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC)
      has been used to cover stents. The maximum polymer-mass on a 16-mm stainless
      steel stent is approximately 2 mg. During manual crimping and simulated
      application, the loss of polymerized HA is negligible. The insoluble HA coating
      has an advantageous inherent antiproliferative effect regarding neointimal
      formation after local vessel wall injury (overstretch model) and leads to a
      reduced inflammatory response compared to uncoated stainless-steel stents, used
      as control, in undiseased pig coronary arteries, over a follow-up period of four
      weeks. Thus, cross-linked HA stent coating warrants further research as an
      interactive degradable biomaterial with an inherent inhibitory effect on
      neointimal formation as a possible biomatrix for local drug delivery to reduce
      restenosis rate.

PMID- 12518962
TI  - Poly(D, L-lactide/epsilon-caprolactone)/hydroxyapatite composites as bone filler:
      an in vivo study in rats.
AB  - In this study, a novel composite bone substitute was implanted in animal models
      (rats) and their in vivo characteristics were examined. A D,L-lactide and E
      caprolactone copolymer (Mw: 80,000; Mn:40,000, and PI:2.00) was synthesized by
      ring-opening polymerization of the respective dimers using stannous octoate as
      the catalyst. The final ratio of D,L-lactide to epsilon-caprolactone obtained by
      1NMR was 60/40. Hydroxyapatite (HA) powder was loaded in the copolymer. The
      HA/copolymer ratio was 60/40 (w/w). These composites were easily shaped by hand.
      Animal tests were performed on mature wistar rats (n=30). Defects were created on
      the proximal, the thickest part of the femur. The bone defects of the first group
      were filled with polymer/HA composite, the second group filled with only HA and
      the third group was left empty. Histologic examination of bone tissues showed new
      bone formation around the yellow-green polymer/HA composite material in the first
      group of animals whereas no evidence of new bone growth was observed in other
      groups.

PMID- 12518963
TI  - Intraindividual comparison of two extracorporeal LDL apheresis methods:
      lipidfiltration and HELP.
AB  - Low density lipoprotein (LDL) apheresis is an effective treatment option for
      patients with severe hypercholesterolemia not adequately responding to diet and
      drug therapy. Membrane differential filtration (MDF), synonymous with double
      filtration plasmapheresis (DFPP), here named Lipidfiltration, and heparin-induced
      extracorporeal LDL-precipitation (HELP) are two of the five methods available for
      extracorporeal LDL apheresis. In this prospective investigation 6 patients with
      severe LDL-hypercholesterolemia and CAD were treated in a cross-over design with
      Lipidfiltration at two stages of technical development and HELP to compare the
      efficacy of these two LDL apheresis methods with respect to lowering and
      modifying plasma lipids and rheologically relevant plasma proteins, especially
      fibrinogen. In total, 44 LDL apheresis sessions were investigated. In weekly
      intervals, patients were treated with consecutive LDL apheresis sessions with
      either Lipidfiltration and HELP, treating identical plasma volumes. In one part
      of the investigation Lipidfiltration was performed with the novel Lipidfilter EC
      50, combined with a newly developed blood and plasma therapy machine allowing
      optimized plasma heating. The results showed that the reduction rates of LDL
      cholesterol, lipoprotein(a) and triglycerides were essentially identical for both
      methods. Also pretreatment levels of total cholesterol, triglycerides, LDL
      cholesterol and HDL-cholesterol were not significantly different in both
      treatment groups. Both methods lead to a significant reduction of serum
      lipoproteins, especially for LDL-cholesterol, which was decreased by 61.4% with
      Lipidfiltration (treated plasma volume: 2998 ml) and 61.3% with HELP (treated
      plasma volume: 3013 ml). With respect to Lipidfiltration LDL-cholesterol
      reduction was more efficient with the novel Lipidfilter EC-50. Mean pretreatment
      HDL cholesterol concentrations remained unchanged. Comparing Cascadeflo AC-1770
      with the novel Lipidfilter EC-50 reduction rates of HDL-cholesterol (17.4% versus
      6.4%) and total protein (17.9% versus 7.8%) were significantly reduced.
      Lipidfiltration and HELP both resulted in a reduction of plasma viscosity and
      hemorheologically relevant plasma proteins, like fibrinogen.

PMID- 12518964
TI  - Hepatitis C therapy with long term remission after renal transplantation.
AB  - Hepatitis C virus infection (HCV) is common in patients with end-stage renal
      disease (ESRD) and long observation periods have shown the detrimental effect of
      HCV infection on patient and graft survival after renal transplantation. At
      present, interferon is the most important agent for the treatment of hepatitis C
      in ESRD; however, limited information exists concerning the long-term response of
      patients who undergo renal transplantation after successful antiviral therapy. We
      describe the evolution of HCV infection in a dialysis patient with hepatitis C
      who was successfully treated with interferon alpha and then underwent renal
      transplantation. He received aggressive immunosuppression during the induction
      phase and for allograft rejection; however, regular screening showed complete
      absence of biochemical and virological relapse of HCV over a 6-year post
      transplantation period. We conclude that interferon can offer excellent response
      in selected dialysis patients with hepatitis C. Alternative strategies with newer
      antiviral agents are currently under active investigation.

PMID- 12518965
TI  - Necrotizing fasciitis successfully treated with extracorporeal blood oxygenation
      and ozonization (EBOO).
AB  - A case of necrotizing fasciitis in a dialysis patient is described. Since
      traditional therapies were unsuccessful, extracorporeal blood oxygenation and
      ozonation (EBOO) was tried. This technique is no longer in the experimental stage
      and is used routinely in our hospital. Patient condition improved radically after
      EBOO.

PMID- 12518966
TI  - Internet and the nephrologist: a new era?

PMID- 12518967
TI  - How chronic self-views influence (and potentially mislead) estimates of
      performance.
AB  - An important source of people's perceptions of their performance, and potential
      errors in those perceptions, are chronic views people hold regarding their
      abilities. In support of this observation, manipulating people's general views of
      their ability, or altering which view seemed most relevant to a task, changed
      performance estimates independently of any impact on actual performance. A final
      study extended this analysis to why women disproportionately avoid careers in
      science. Women performed equally to men on a science quiz, yet underestimated
      their performance because they thought less of their general scientific reasoning
      ability than did men. They, consequently, were more likely to refuse to enter a
      science competition.

PMID- 12518968
TI  - The silence of the library: environment, situational norm, and social behavior.
AB  - On the basis of the idea that situational norms are mentally represented as
      associations between environments and normative behavior, it was proposed that an
      environment can automatically direct normative behavior. More specifically, when
      situational norms are well-established (e.g., when entering the library, one
      should be silent), an environment is capable of automatically activating mental
      representations of normative behavior and the behavior itself. In these
      experiments, participants were exposed to pictures of environments, and effects
      on accessibility of representations of normative behavior and on actual behavior
      were assessed. Results indicated that representations of behavior and actual
      behavior itself are activated automatically when (a) goals to visit the
      environment are active and (b) strong associations between environment and
      normative behavior are established.

PMID- 12518969
TI  - Self-esteem and memory.
AB  - This article describes two potential bases for memory bias associated with global
      self-esteem. According to the mood-congruence model, activation of either
      dimension of self-esteem (self-competence or self-liking) produces an affective
      state that facilitates retrieval of traces that are consistent with that state
      while hindering retrieval of traces that are inconsistent. According to the
      relevance model, activation of either dimension results in superior encoding of
      matching negative content by individuals who are low on the dimension. Three
      studies were conducted to determine which model best accounts for the pattern of
      bias across distinct content categories. Results were generally consistent with
      the relevance model.

PMID- 12518970
TI  - Culture and judgment of causal relevance.
AB  - The authors hypothesized that because the causal theories of East Asians were
      more holistic and complex than those of Americans, the amount of information
      considered before making a final attribution would be larger for East Asians than
      for Americans. This hypothesis was supported through 4 studies. When participants
      attempted to explain a deviant behavior (Study 1) or a prosocial behavior (Study
      2), Korean participants took into consideration a greater amount of information
      than did either American or Asian American participants. Study 3 replicated the
      findings of Studies 1 and 2 within each culture. Finally, Study 4 established a
      link between the present findings and past research on culture and attribution.
      Namely, Study 4 found that Koreans made more external attributions than Americans
      because Koreans considered more information than did Americans.

PMID- 12518971
TI  - Pancultural self-enhancement.
AB  - The culture movement challenged the universality of the self-enhancement motive
      by proposing that the motive is pervasive in individualistic cultures (the West)
      but absent in collectivistic cultures (the East). The present research posited
      that Westerners and Easterners use different tactics to achieve the same goal:
      positive self-regard. Study 1 tested participants from differing cultural
      backgrounds (the United States vs. Japan), and Study 2 tested participants of
      differing self-construals (independent vs. interdependent). Americans and
      independents self-enhanced on individualistic attributes, whereas Japanese and
      interdependents self-enhanced on collectivistic attributes. Independents regarded
      individualistic attributes, whereas interdependents regarded collectivistic
      attributes, as personally important. Attribute importance mediated self
      enhancement. Regardless of cultural background or self-construal, people self
      enhance on personally important dimensions. Self-enhancement is a universal human
      motive.

PMID- 12518972
TI  - Is who you are who you're talking to? Interpersonal style and complementarity in
      mixed-sex interactions.
AB  - To investigate interpersonal theory, the authors examined the social behavior of
      112 previously unacquainted male-female pairs collaborating on a joint task.
      Structural equation modeling analyses provided clear evidence of complementarity:
      In addition to trait affiliation and dominance both predicting situational
      behavior, each interaction partner's behavior influenced the other's in
      accordance with the theory, eliciting similar levels of affiliation and opposite
      levels of dominance. There were also clear biases related to participants'
      interpersonal traits: When behavior, as indexed by observers, was held constant,
      more trait affiliative participants tended to view themselves and their partner
      as warmer during the interaction; likewise, more trait dominant participants
      perceived themselves to act more dominantly than they actually did. Throughout,
      there were no sex differences.

PMID- 12518973
TI  - Differentiating autonomy from individualism and independence: a self
      determination theory perspective on internalization of cultural orientations and
      well-being.
AB  - On the basis of self-determination theory (R. M. Ryan & E. L. Deci, 2000) and
      cultural descriptions drawn from H. C. Triandis (1995), the authors hypothesized
      that (a) individuals from different cultures internalize different cultural
      practices; (b) despite these differences, the relative autonomy of individuals'
      motivation for those practices predicts well-being in all 4 cultures examined;
      and (c) horizontal practices are more readily internalized than vertical
      practices across all samples. Five hundred fifty-nine persons from South Korea,
      Russia, Turkey and the United States participated. Results supported the
      hypothesized relations between autonomy and well-being across cultures and
      gender. Results also suggested greater internalization of horizontal relative to
      vertical practices. Discussion focuses on the distinction between autonomy and
      individualism and the relative fit of cultural forms with basic psychological
      needs.

PMID- 12518974
TI  - Perceptions of stranger and acquaintance rape: the role of benevolent and hostile
      sexism in victim blame and rape proclivity.
AB  - In Studies 1 and 2, after reading an acquaintance-rape but not a stranger-rape
      scenario, higher benevolent sexist but not hostile sexist participants blamed the
      victim significantly more. In Study 2, higher hostile sexist but not benevolent
      sexist male participants showed significantly greater proclivity to commit
      acquaintance (but not stranger) rape. Studies 3 and 4 supported the hypothesis
      that the effects of benevolent sexism and hostile sexism are mediated by
      different perceptions of the victim, as behaving inappropriately and as really
      wanting sex with the rapist. These findings show that benevolent sexism and
      hostile sexism underpin different assumptions about women that generate sexist
      reactions toward rape victims.

PMID- 12518975
TI  - Once hurt, twice hurtful: how perceived regard regulates daily marital
      interactions.
AB  - A daily diary study examined how chronic perceptions of a partner's regard affect
      how intimates interpret and respond to daily relationship stresses. Spouses each
      completed a diary for 21 days. Multilevel analyses revealed that people who felt
      less positively regarded read more into stressful events than did people who felt
      highly regarded, feeling more hurt on days after acute threats, such as those
      posed by a moody or ill-behaved partner. Intimates who felt less valued responded
      to feeling hurt by behaving badly toward their partner on subsequent days. In
      contrast, intimates who felt more valued responded to feeling hurt by drawing
      closer to their partner. Ironically, chronically activated needs for
      belongingness might lead people who are trying to find acceptance to undermine
      their marriage.

PMID- 12518976
TI  - Thinking of you: nonconscious pursuit of interpersonal goals associated with
      relationship partners.
AB  - The mere psychological presence of relationship partners was hypothesized to
      trigger interpersonal goals that are then pursued nonconsciously. Qualitative
      data suggested that people tend to pursue different interpersonal goals within
      different types of relationships (e.g., mother, best friend, coworker). In
      several studies, priming participants' relationship representations produced goal
      directed behavior (achievement, helping, understanding) in line with the
      previously assessed goal content of those representations. These findings support
      the hypothesis that interpersonal goals are component features of relationship
      representations and that mere activation of those representations, even in the
      partner's physical absence, causes the goals to become active and to guide
      behavior nonconsciously within the current situation.

PMID- 12518977
TI  - Portrait of the self-enhancer: well adjusted and well liked or maladjusted and
      friendless?
AB  - Research has variously portrayed self-enhancement as an indicator of narcissistic
      defensiveness or as a concomitant of mental health. To address this controversy,
      the present study used multiple measures of self-enhancement along with multiple
      measures and judges of mental health, comprehensively assessing their
      relationship. The results indicated that self-enhancement is positively
      associated with multiple indicators of mental health and with a more favorable
      impact on others. Discussion centers on a reconciliation of discrepant portraits
      of the self-enhancer.

PMID- 12518978
TI  - "I know you self-handicapped last exam": gender differences in reactions to self
      handicapping.
AB  - Past research has shown that self-handicapping involves the trade-off of ability
      related attributional benefits for interpersonal costs. Study 1 examined whether
      perceiver or target sex moderates impressions of self-handicapping targets.
      Although target sex was not an important factor, female perceivers were
      consistently more critical of behavioral self-handicappers. Two additional
      studies replicated this gender difference with variations of the handicap. Study
      3 examined the motives inferred by perceivers and found that women not only view
      self-handicappers as more unmotivated but also report greater suspicion of self
      handicapping motives; furthermore, these differences in perceived motives
      mediated sex differences in reactions to self-handicappers. Implications for the
      effectiveness of self-handicapping as an impression management strategy are
      discussed.

PMID- 12518979
TI  - Seeking self-evaluative feedback: the interactive role of global self-esteem and
      specific self-views.
AB  - People who verify a negative self-view expose themselves to criticism and
      rejection. Because people with low global self-esteem are hurt more by negative
      feedback than are people with high global self-esteem, the authors predicted that
      they would be less apt to verify a negative self-view in a more specific domain.
      Three investigations found support for this hypothesis. In all 3 investigations,
      high self-esteem participants sought (or tended to seek) self-verifying feedback,
      even if it was negative, but low self-esteem participants sought (or tended to
      seek) positive feedback, even if it was nonself-verifying. These findings show
      that low self-esteem people are especially concerned with self-protection and
      that global self-esteem and specific self-views interact to guide people's
      responses to self-evaluative feedback.

PMID- 12518980
TI  - Stability of self-esteem across the life span.
AB  - Two studies examined the rank-order stability of self-esteem from age 6 to 83:
      Study 1 was a meta-analysis of 50 published articles (N = 29,839) and Study 2
      analyzed data from 4 large national studies (N = 74,381). Self-esteem showed
      substantial continuity over time (disattenuated correlations ranged from the .50s
      to .70s), comparable to the stability found for personality traits. Both studies
      provided evidence for a robust developmental trend: Self-esteem stability was low
      during childhood, increased throughout adolescence and young adulthood, and
      declined during midlife and old age. This trend could not be explained by age
      differences in the reliability of self-esteem measures, and generally replicated
      across gender, ethnicity, self-esteem scale, nationality (U.S. vs. non-U.S.), and
      year of publication.

PMID- 12518981
TI  - Negative affectivity and drug use in adolescent boys: moderating and mediating
      mechanisms.
AB  - This investigation examined variables that might qualify or detail the widely
      accepted relation between negative affectivity and drug use in adolescent boys.
      In Study 1, 311 boys (15-17 years old) completed inventories of negative
      affectivity, positive affectivity, constraint, delinquency, peer delinquency, and
      drug use. Negative affectivity was positively related to drug use, but only for
      individuals exhibiting high peer delinquency or low constraint. Study 2 examined
      mechanisms for this relation by following up 143 of the participants at ages 17
      20 years. Delinquency and peer delinquency mediated the relation between negative
      affectivity and later drug use. These findings suggest that the relation between
      negative affectivity and drug use is best understood within the context of other
      drug use risk factors.

PMID- 12518982
TI  - Self-critical perfectionism and daily affect: dispositional and situational
      influences on stress and coping.
AB  - This study of university students (64 men and 99 women) examined both
      dispositional and situational influences of self-critical (SC) perfectionism on
      stress and coping, which explain its association with high negative affect and
      low positive affect. Participants completed questionnaires at the end of the day
      for 7 consecutive days. Structural equation modeling indicated that the relation
      between SC perfectionism and daily affect could be explained by several
      maladaptive tendencies associated with SC perfectionism (e.g., hassles, avoidant
      coping, low perceived social support). Multilevel modeling indicated that SC
      perfectionists were emotionally reactive to stressors that imply possible
      failure, loss of control, and criticism from others. As well, certain coping
      strategies (e.g., problem-focused coping) were ineffective for high-SC
      perfectionists relative to low-SC perfectionists.

PMID- 12518983
TI  - Dimerization, translocation and localization of Ku70 and Ku80 proteins.
AB  - The Ku protein is a complex of two subunits, Ku70 and Ku80, and was originally
      identified as an autoantigen recognized by the sera of patients with autoimmune
      diseases. The Ku protein plays a key role in multiple nuclear processes, e.g.,
      DNA repair, chromosome maintenance, transcription regulation, and V(D)J
      recombination. The mechanism underlying the regulation of all the diverse
      functions of Ku is still unclear, although it seems that Ku is a multifunctional
      protein that works in nuclei. On the other hand, several studies have reported
      cytoplasmic or cell surface localization of Ku in various cell types. To clarify
      the fundamental characteristics of Ku, we have examined the expression,
      heterodimerization, subcellular localization, chromosome location, and molecular
      mechanisms of the nuclear transport of Ku70 and Ku80. The mechanism that
      regulates for nuclear localization of Ku70 and Ku80 appears to play, at least in
      part, a key role in regulating the physiological function of Ku in vivo.

PMID- 12518984
TI  - Drinking beer reduces radiation-induced chromosome aberrations in human
      lymphocytes.
AB  - We here investigated and reported the effects of beer drinking on radiation
      induced chromosome aberrations in blood lymphocytes. Human blood that was
      collected either before or after drinking a 700 ml beer was in vitro irradiated
      with 200 kVp X rays or 50 keV/microm carbon ions. The relation between the
      radiation dose and the aberration frequencies (fragments and dicentrics) was
      significantly (p < 0.05) lower for lymphocytes collected 3 h after beer drinking
      than those before drinking. Fitting the dose response to a linear quadratic model
      showed that the alpha term of carbon ions was significantly (p < 0.05) decreased
      by beer drinking. A decrease of dicentric formation was detected as early as 0.5
      h after beer drinking, and lasted not shorter than 4.5 h. The mitotic index of
      lymphocytes was higher after beer drinking than before, indicating that a
      division delay would not be responsible for the low aberrations induced by beer
      drinking. An in vitro treatment of normal lymphocytes with 0.1 M ethanol, which
      corresponded to a concentration of 6-times higher than the maximum ethanol
      concentration in the blood after beer drinking, reduced the dicentric formation
      caused by X-ray irradiation, but not by carbonion irradiation. The beer-induced
      reduction of dicentric formation was not affected by serum. It is concluded that
      beer could contain non-ethanol elements that reduce the chromosome damage of
      lymphocytes induced by high-LET radiation.

PMID- 12518986
TI  - Models for mixed irradiation with a 'reciprocal-time' pattern of the repair
      function.
AB  - Suzuki presented models for mixed irradiation with two and multiple types of
      radiation by extending the Zaider and Rossi model, which is based on the theory
      of dual radiation action. In these models, the repair function was simply assumed
      to be semi-logarithmically linear (i.e., monoexponential), or a first-order
      process, which has been experimentally contradicted. Fowler, however, suggested
      that the repair of radiation damage might be largely a second-order process
      rather than a first-order one, and presented data in support of this hypothesis.
      In addition, a second-order repair function is preferred to an n-exponential
      repair function for the reason that only one parameter is used in the former
      instead of 2n-1 parameters for the latter, although both repair functions show a
      good fit to the experimental data. However, according to a second-order repair
      function, the repair rate depends on the dose, which is incompatible with the
      experimental data. We, therefore, revised the models for mixed irradiation by
      Zaider and Rossi and by Suzuki, by substituting a 'reciprocal-time' pattern of
      the repair function, which is derived from the assumption that the repair rate is
      independent of the dose in a second-order repair function, for a first-order one
      in reduction and interaction factors of the models, although the underlying
      mechanism for this assumption cannot be well-explained. The reduction factor,
      which reduces the contribution of the square of a dose to cell killing in the
      linear-quadratic model and its derivatives, and the interaction factor, which
      also reduces the contribution of the interaction of two or more doses of
      different types of radiation, were formulated by using a 'reciprocal-time'
      pattern of the repair function. Cell survivals calculated from the older and the
      newly modified models were compared in terms of the dose-rate by assuming various
      types of single and mixed irradiation. The result implies that the newly modified
      models for mixed irradiation can express or predict cell survival more accurately
      than the older ones, especially when irradiation is prolonged at low dose rates.

PMID- 12518985
TI  - Relative biological effectiveness of 290 MeV/u carbon ions for the growth delay
      of a radioresistant murine fibrosarcoma.
AB  - The relative biological effectiveness (RBE) for animal tumors treated with
      fractionated doses of 290 MeV/u carbon ions was studied. The growth delay of NFSa
      fibrosarcoma in mice was investigated following various daily doses given with
      carbon ions or those given with cesium gamma-rays, and the RBE was determined.
      Animal tumors were irradiated with carbon ions of various LET (linear energy
      transfer) in a 6-cm SOBP (spread-out Bragg peak), and the isoeffect doses; i.e.
      the dose necessary to induce a tumor growth delay of 15 days were studied. The
      iso-effect dose for carbon ions of 14 and 20 keV/microm increased with an
      increase in the number of fractions up to 4 fractions. The increase in the
      isoeffect dose with the fraction number was small for carbon ions of 44
      keV/microm, and was not observed for 74 keV/microm. The alpha and beta values of
      the linear-quadratic model for the radiation dose-cell survival relationship were
      calculated by the Fe-plot analysis method. The alpha values increased linearly
      with an increase in the LET, while the beta values were independent of the LET.
      The alpha/beta ratio was 129 +/- 10 Gy for gamma-rays, and increased with an
      increase in the LET, reaching 475 +/- 168 Gy for 74 keV/microm carbon ions. The
      RBE for carbon ions relative to Cs-137 gamma-rays increased with the LET. The RBE
      values for 14 and 20 keV/microm carbon ions were 1.4 and independent of the
      number of fractions, while those for 44 and 74 keV/microm increased from 1.8 to
      2.3 and from 2.4 to 3.0, respectively, when the number of fractions increased
      from 1 to 4. Increasing the number of fractions further from 4 to 6 was not
      associated with an increase in the RBE. These results together with our earlier
      study on the skin reaction support the use of an RBE of 3.0 in clinical trials of
      80 keV/microm carbon beams. The RBE values for low doses of carbon beams were
      also considered.

PMID- 12518987
TI  - Changes in histological construction and decrease in 3H-QNB binding in the rat
      brain after prenatal X-irradiation.
AB  - To elucidate the mechanisms involved in deleterious neuronal and behavioral
      changes after prenatal ionizing irradiation, in vitro muscarinic acetylcholine
      (mACh) receptor binding and histological construction were investigated in 9-week
      old rat brains after 1.5 Gy X-ray exposure on embryonic day 15 (E15). A gross
      anatomical examination with a magnetic-resonance imaging system showed an
      irregular tissue construction in the hippocampus and cortex of the irradiated rat
      brain. Histological sections stained with hematoxylin and eosin also indicated
      that the structures of the hippocampus and cortex were obviously changed. In
      irradiated rats, the laminar structure of pyramidal cells was selectively
      deranged in the CA1 region. In vitro 3H-Quinuclidinyl benzilate binding in the
      hippocampus was significantly decreased (about 10%) in prenatal irradiated rats
      compared to that in sham-treated rats. On the other hand, no significant change
      in mACh receptor binding was observed in the cerebral cortex. The present study
      revealed that prenatal exposure to ionizing radiation may induce dysfunction of
      the cholinergic neuronal systems, especially in the hippocampus, resulting in
      deleterious changes in memory and behavior.

PMID- 12518988
TI  - Radiosensitization by overexpression of the nonphosphorylation form of IkappaB
      alpha in human glioma cells.
AB  - To assess the role of NF-kappaB in cellular radiosensitivity, we constructed
      mutated IkappaB expression plasmids for SY-IkappaB (with mutations at residues of
      32, 36 and 42) expression in human malignant glioma cells (radiosensitive MO54
      and radioresistant T98 cells), giving respective cell types referred to as MO54
      SY4 and T98-SY14. Both of the clones expressing SY-IkappaB became radiosensitive,
      compared with the parental MO54 and T98 cells. A treatment with herbimycin A or
      genistein did not change the radiosensitivity of cells expressing SY-IkappaB, but
      made both the MO54 and T98 parental cells more sensitive to ionizing radiation. A
      treatment with TNF-alpha induced DNA fragmentation and apoptosis in cells
      expressing SY-IkappaB, but not in MO54 and T98 cells. The survival after X-ray
      exposure of the parental MO54 cells was slightly increased by a TNF-alpha
      treatment, but that of the parental T98 cells did not change. The change in
      sensitivity to ultra-violet (UV) radiation and adriamycin in MO54-SY4 cells was
      very similar to that for X-ray sensitivity, but no change was observed in T98
      SY14 cells. Significant sublethal damage repair was observed in T98 cells,
      whereas MO54 cells showed little repair activity. The expression of p53 was
      enhanced in the parental MO54 cells, while the p53 levels in the MO54-SY4, and in
      the parent and clonal T98 cells, did not change. Our data suggest that the serine
      and tyrosine phosphorylation of IkappaB-alpha may play a role in determining the
      radiosensitivity of malignant glioma cells.

PMID- 12518989
TI  - Radioprotective effects of 2-imino-3-[(chromone-2-yl)carbonyl] thiazolidines
      against gamma-irradiation in mice.
AB  - A series of 2-imino-3-[(chromone-2-yl) carbonyl]thiazolidines substituted at the
      C-5 and/or C-7 positions of a chromone ring were synthesized. The in vivo
      toxicity and radioprotective efficacy of these agents were evaluated in male NMRI
      mice against cobalt-60 gamma-rays. The LD50 values as determined by a Probit
      analysis, were 659, 1216 and 790 mg/kg for compounds, 2, 3 and 4, respectively.
      For studying radioprotective effects, one half of the toxic LD50 values were
      used, namely 330, 605 and 395 mg/kg for compounds 2, 3 and 4, respectively. The
      dose reduced factor (DRF) was determined by dividing the LD50/30 values obtained
      from the radiation survival curve in the presence of a radioprotective agent by
      the LD50/30 value obtained from a control radiation survival curve. A compound
      with a hydroxyl group substituent at the C-5 position afforded better
      radioprotective activity than those without this substituent. The radioprotective
      effect of chromone having a hydroxyl group at only the C-7 position was similar
      to that of the unsubstituted chromone. The most active compound has hydroxyl
      groups at the C-5 and C-7 positions of the chromone ring; it had a DRF of 1.48.

PMID- 12518990
TI  - Immunohistochemical study on cellular origins of rat lung tumors induced by
      inhalation exposures to plutonium dioxide aerosols as compared to those by X-ray
      irradiation.
AB  - Immunohistochemical examinations were performed on rat pulmonary tumors induced
      by inhalation exposures to 239PuO2 aerosols, or by X-ray-irradiation to identify
      and compare cellular origins or, in turn, target cells at risk for radiation
      carcinogenesis. Both plutonium-induced and X-ray-induced pulmonary tumors
      appeared to occur from the lower respiratory tract epithelium through bronchioles
      into alveoli, and were histopathologically diagnosed as adenoma, adenocarcinoma,
      adenosquamous carcinoma, and squamous cell carcinoma. Immunohistochemical
      staining of neoplastic lesions using rabbit polyclonal antibodies to rat
      surfactant apoprotein A specific for alveolar type II pneumocytes, and Clara cell
      antigen specific for nonciliated bronchiolar Clara cells, showed that most of the
      adenomatous and adenocarcinomatous lesions from plutonium-exposed or X-irradiated
      rats were positive for either or both antigens, while, in contrast, adenosquamous
      and squamous lesions were mostly negative for both antigens. Even though there
      were some differences in the proportions and distributions of immunoreactive
      cells between plutonium- and X-ray-induced tumors and among neoplastic lesions,
      the results indicate that radiation-induced pulmonary adenomas and
      adenocarcinomas mostly originate from either alveolar type II pneumocytes or
      bronchiolar Clara cells, while adenosquamous and squamous carcinomas may be
      derived from the other epithelial cell components, or might have lost specific
      antigenicity during their transforming differentiation.

PMID- 12518991
TI  - Dose-response relationship for lifetime excess mortality and temporal pattern of
      manifestation in mice irradiated neonatally with gamma rays.
AB  - The dose-response relationships for the lifetime excess mortality and temporal
      distribution of excess mortality were analysed using a data set from an
      experiment on the long-term effects of gamma irradiation in neonatal mice. The
      excess mortality was calculated based on an assumption that any increase in the
      mortality rate was attributable to radiation exposure. The dose-response
      relationship for the lifetime excess mortality was convex upward, whereas the
      shortening of the mean life span was proportional to the dose. The excess
      mortality at 1 Gy was estimated to be 35.6%. The relative risk decreased markedly
      with increasing age. However, the mortality rate in the irradiated group was
      persistently higher than the background rate of death, and the absolute risk
      increased with age. A logistic specification was used to analyze the temporal
      distribution of the excess mortality. The results of the analysis indicated a
      dose-dependent shortening of the latent period and a broadening of the
      distribution.

PMID- 12518992
TI  - The phosphatidylinositol-3 kinase pathway is not essential for insulin-like
      growth factor I receptor-mediated clonogenic radioresistance.
AB  - The insulin-like growth factor I receptor (IGF-IR) is known to induce clonogenic
      radioresistance in cells following ionizing irradiation. To explore the
      downstream signaling pathways, we focused on the phosphatidylinositol-3 kinase
      (PI3-K) pathway, which is thought to be the primary cell survival signal
      originating from the receptor. For this purpose, R- cells deficient in the
      endogenous IGF-IR were used as a recipient of the human IGF-IR with or without
      mutations at potential PI3-K activation sites: NPXY950 and Y1316XXM. Mutants with
      double mutation at Y950/Y1316 exhibited not abrogated, but reduced activation of
      IRS-1, PI3-K, and Akt upon IGF-I stimulation. However, the mutants had the same
      clonogenic radioresistance as cells with wild type (WT) receptors. Neither
      wortmannin nor LY294002, specific inhibitors of PI3-K, affected the
      radioresistance of cells with WT receptors at concentrations specific for PI3-K.
      Collectively, these results indicate that the PI3-K pathway is not essential for
      IGF-IR-mediated clonogenic radioresistance.

PMID- 12518993
TI  - Dose estimation by ESR on tooth enamel from two workers exposed to radiation due
      to the JCO accident.
AB  - ESR dosimetry is useful to estimate the external dose for the general population
      as well as for occupational workers in a nuclear emergency. Three teeth were
      extracted from two exposed workers (A and B) related to the JCO criticality
      accident. Tooth enamel was carefully separated from other tooth parts and
      subjected to ESR dosimetry. Doses equivalent to the gamma-ray dose of 60Co were
      estimated as follows: for worker A, the buccal and lingual sides of the eighth
      tooth in the upper right side, 11.8 +/- 3.6 and 12.0 +/- 3.6 Gy, respectively;
      for worker B, the buccal and lingual sides of the fourth tooth in the upper right
      side and the fifth tooth in the upper left side, 11.3 +/- 3.4 and 10.8 +/- 3.3
      Gy, 11.7 +/- 3.5 and 11.4 +/- 3.4 Gy, respectively. The estimated doses were
      found to be similar and not dependent on the tooth positions, whether the buccal
      or lingual sides in each tooth.

PMID- 12518995
TI  - Erythrocyte pyruvate kinase activity during chemotherapy in children with
      leukemia and lymphoma.
AB  - OBJECTIVES: To determine both erythrocyte pyruvate kinase activity (ePKA) at the
      time of diagnosis of patients with acute leukemia or lymphoma and the differences
      in the ePKA profiles during the malignant disease and its chemotherapy. METHODS:
      A prospective, longitudinal clinical study was performed involving 57 patients,
      10 were the ones with relapse of acute lymphoblastic leukemia, 32 were the ones
      with acute lymphoblastic leukemia (ALL) and 15 were the ones with lymphoma. None
      of the subjects in this study group received treatment or blood transfusion
      before the study, except the ones diagnosed with relapse of ALL. Forty two
      healthy children were also selected to form the control group. In order to
      measure ePKA, blood samples were taken for five times, with 1.5 months apart
      between each other during the study. Statistical analysis were done by using
      Wilcoxon's signed rank test, Kruskall-Wallis with Mann-Whitney U Test and
      Spearman rank correlation coefficient test. RESULTS: The ePKA of the patients
      with relapse of ALL, and ALL, but not the patients with lymphoma, at the time of
      diagnosis were found to be lower compared to the one's in the control group
      (respectively p = 0.001, p = 0.003). The comparison between the first ePKA
      samples and the third ePKA samples of the patients with both ALL and lymphoma
      showed a significant increase (respectively p = 0.006, and p = 0.047).
      CONCLUSION: The measurement of ePKA can be considered for follow-up the
      neoplastic treatment due to the fact that it is detected to be low in leukemia
      and relapse of ALL and in normal values after chemotherapy. However, more long
      term studies, including more number of cases, are required to be carried out in
      order to prove the accuracy of this hypothesis. (Tab. 2, Fig. 1, Ref. 28.)

PMID- 12518994
TI  - Study of the content of heavy metals related to environmental load in urban areas
      in Slovakia.
AB  - It is natural for the man to take care of his environment so the negative
      influences of intensification of industrial and agricultural production and the
      entire process of pollution are kept at minimum or eliminated as early as
      possible. However, they must first be identified. BACKGROUND: companion animals,
      for example dogs, are a very good indicator of the pollution load on the
      environment. They inhabit the same space as humans and are exposed to the action
      of the same pollutants. The most important role in contamination of the
      environment with heavy metals is played by emissions of different origin. For
      that reason it is appropriate and advantageous to evaluate the load on the man by
      parallel evaluation of the heavy metal load on dogs, particularly in large town
      agglomerations. MAIN PURPOSE: the aim of the study was to compare and evaluate
      the content of three heavy metals, cadmium, arsenic and lead, in the hair of dogs
      from two largest town agglomerations of Slovakia, Bratislava and Kosice. In
      addition to that, an effort was made to compare the environmental load in
      Bratislava and Kosice by using the dog as a bioindicator of environmental
      pollution with heavy metals and to quantify the content of heavy metals in dog'
      hair. METHODS: The generally low level of heavy metals in biological material
      makes it impossible to use common analytical methods. In our study the samples of
      dog hair were analysed using the method of atomic absorption spectrometry. The
      measurements were carried out on a Perkin-Elmer spectrometer, model 5000, using
      the following wavelengths: 228.8 nm for Cd, 193.7 nm for As and 283.3 nm for Pb.
      The results of analyses are presented as means. The concentrations of Cd, As and
      Pb are expressed in microg/kg dog hair. Statistical evaluation of results was
      carried out by means of Student's t-test. RESULTS: The mean values of heavy
      metals in the set of dogs from Bratislava reached the following levels: 38.09
      microg/kg for Cd, 111.07 microg/kg for As, and 729.59 microg/kg for Pb. The set
      of dogs from Kosice allowed us to detect the following mean values: 22.21
      microg/kg for Cd, 79.87 microg/kg for As, and 542.49 microg/kg for Pb. The mean
      values for the entire Slovak territory reached 27.39 microg/kg for Cd, 90.06
      microg/kg for As, and 601.96 microg/kg for Pb. The comparison of the first two
      experimental sets of data with the Slovak mean values showed highly significant
      differences in arithmetic means (p < 0.01) for Cd and significant (p < 0.05) for
      As with the Bratislava set reaching higher values. No statistically significant
      differences were observed with regard to Pb. CONCLUSION: The study confirms the
      need for further research in this area with the dog as a bioindicator involving
      also other environmental loads not only that resulting from heavy metals. It
      indicates the importance of risk assessment in relation to environmental
      pollution. As the studies on animals are applicable also to the human population
      it appears very appropriate to use also this indirect way to point out to the
      negative impact of the polluted environment. Lead, cadmium and arsenic are the
      heavy metals that raise particular concern because of their wide-spectrum
      negative influences on live organisms. (Tab. 4, Fig. 5, Ref 28.)

PMID- 12518996
TI  - Human information processing in different age.
AB  - The aim of investigation was to study the aging pecularities of information
      processing organization. 60 men and 90 women in four age groups: 30-39, 40-49, 50
      59 and 60-65 were examined. The information processing was modeled by special
      computer test with working algorithm changes. The time and accuracy of each
      assignment were registered for each person. The psychophysiological mechanisms of
      informational processing were studied by informative mathematical methods. The
      results are showed that within the aging reduction of perception, processing and
      speed of reaction in older. As a result of the negative influence of aging shows
      the decline of mental activity efficiency. Aging decrease on mental capability
      provokes the compensation of psychophysiological mechanisms of adaptation. The
      main mechanism increases the psychophysiological organization stochastic and
      changes the type organization in informational processing to a self-finishing
      quest response. (Tab. 5, Ref. 22.)

PMID- 12518997
TI  - Small aneurysms as a cause of thromboembolic stroke.
AB  - OBJECTIVE AND IMPORTANCE: A small percentage of patients with intracranial
      aneurysms present with embolic stroke distal to the site of the aneurysm.
      Thromboembolism typically occurs in large or giant aneurysms where reduction of
      flow within the aneurysm is thought to increase the possibility of clot
      formation. Only a few examples are available in the literature of patients with
      smaller aneurysms who develop embolic infarction distal to the lesion. We have
      experience with two such patients with an apparent common pathophysiology.
      CLINICAL PRESENTATION: Patient 1 with a distal left middle cerebral artery
      infarct was found to have an 18 mm carotid artery bifurcation aneurysm (patient
      age 49 years). Patient 2 had a 7 mm right middle cerebral artery aneurysm with a
      small distal embolus (patient age 65 years). At surgery both patients were found
      to have atherosclerotic disease involving the aneurysm base and parent vessel. In
      each instance, the aneurysm was opened during temporary vessel occlusion and
      microendarterectomy was performed. Occlusion of one of the major arterial
      branches exiting the aneurysm was also present with anterior cerebral artery
      occlusion in the case of ICA bifurcation lesion and MCA branch occlusion in the
      case of the MCA aneurysm. Both patients made a good recovery following surgery.
      CONCLUSION: In small aneurysms with atherosclerotic disease distal
      thromboembolism may occur. Surgical treatment with microendarterectomy is
      appropriate to prevent further emboli and potential for subarachnoid hemorrhage.
      (Fig. 5, Ref. 16.)

PMID- 12518998
TI  - The effect of nickel sulphate, potassium dichromate, cobalt nitrate and cadmium
      sulphate on the proteins of cellular contacts and actin skeleton of cultivated
      human keratinocytes.
AB  - The authors tested the effects of known allergens, namely nickel sulphate,
      potassium dichromate, cobalt nitrate and cytotoxic cadmium sulphate on the
      proteins of cellular contacts (vinculin, talin, E-cadherin, desmoplaktin) and
      actin cytoskeleton (actin filaments) of cultivated human keratinocytes. The
      localisation of proteins of cellular contacts was detected by means of direct
      immunofluorescence. The authors have detected a decrease in, and destruction of
      cellular contact proteins and actin cytoskeleton after testing the effect of all
      allergens, while the most significant changes were detected in E-cadherin,
      vunkulin and actin filaments. Desmoplaktin and talin were less damaged. Potassium
      dichromate caused damage already in concentration of 1 microg/ml. A similar
      effect of the other two tested haptanes was brought about in concentration being
      100-fold higher. CONCLUSION: the gained results indicate that the investigation
      of cellular contact proteins and actin cytoskeleton of cultivated human
      keratinocytes can possibly become a part of the testing of allergy-triggering
      potential of chemical substances. (Tab. 1, Fig. 4, Ref. 18.)

PMID- 12518999
TI  - The effect of the pulsatile electromagnetic field in patients suffering from
      chronic obstructive pulmonary disease and bronchial asthma.
AB  - Pulsatile electromagnetotherapy (PETh) stimulates biological tissues and
      processes; it modulates ion exchange across cell membranes and thus regulates the
      tone of smooth muscles. On the basis of these effects we hypothetized that PETh
      might treat COPD and bronchial asthma. We examined 117 (61 females, 56 males)
      adult patients who were decided in 4 groups. The 1st consisted of 16 patients
      with COPD who were treated by PETh and pharmacologically. The 2nd group (control)
      consisted of 24 patients with COPD who were treated only with medicaments. The
      3rd group consisted of 37 asthmatics, treated by PETh and medicaments. The 4th
      group (control) consisted of 40 asthmatics treated only with medicaments. The
      effectiveness of PETh was assessed by lung function tests, which were performed
      using a Spirometer 100 Handi (Germany). We measured FVCex, FEV1, percentage of
      FEV1/FVCex, MEF25, 50, 75, PEF and registered the flow-volume loops. PETh was
      applied by apparatus MTU 500H (Therapy System, Czech Republic). It was
      administered 10 doses; once daily for 20 min, with a frequency of 4.5 Hz and a
      magnetic induction 3 T. The initial 3 doses were about 25% lower then the later
      doses. PETh was very effective in patients with COPD. The measured indexes
      improved about 200-660 ml or ml x s(-1), except FVC. PETh was less effective in
      asthmatics. Most indices improved without statistical significance, about 50-620
      ml or ml x s(-1). The indices of FEV1/FVC and MEF25 deteriorated. The changes in
      controls without PETh were very small. (Tab. 2, Fig. 1, Ref. 19.)

PMID- 12519000
TI  - Rescue systemic thrombolysis during cardiopulmonary resuscitation.
AB  - The main goal of the cardiopulmonary resuscitation is good neurological outcome.
      The primary ischaemic insult initiates a multitude of coagulation and
      inflammatory cascades resulting in cytotoxic brain oedema, necrosis and
      apoptosis. Thrombolytic agents may have experimentally and clinically significant
      beneficial effects in non-traumatic cardiac arrest. Prospective clinical trials
      show that thrombolytic therapy combined with heparin is feasible, safe and
      effective during resuscitation. We demonstrate three cases of successful systemic
      thrombolysis during in hospital CPR in cancer patients. Two patients were
      successfully resuscitated from cardiac arrest with streptase bolus (500.000 IU)
      and infusion (100,000/hr). One patient with pulmonary embolism and gynecological
      bleeding were treated with bolus (10,000 IU) and infusion of heparin (1,000
      IU/hr) and successfully resuscitated. We observed a very good neurological
      outcome in all 3 cases following rescue thrombolysis and standard CPR. Two
      patients were discharged from hospital in good neurological outcome. One patient
      died on ICU on 10th day due to myocardial re-infarction and biventricular
      failure. Systemic thrombolysis is safe and effective treatment modality during
      resuscitative efforts even in cancer patients. In oncological patients with
      dissemination and/or bleeding heparin therapy should be considered due to better
      clinical control. (Ref. 17.)

PMID- 12519001
TI  - Risks of antibiotic treatment.
AB  - Adverse effects of antibiotics can cause a failure of antibiotic treatment. The
      authors give a survey of antibiotic toxicity manifestations, according to the
      target organ systems, with emphasis on identification of at-risk patients and on
      possible prevention of particular adverse effects. Although antibiotics belong to
      relatively safe pharmaceuticals, many of them can be a cause of a serious damage
      to the human organism. Beta-lactam antibiotics are considered the least
      dangerous. A considerable number of adverse effects, especially the dose
      dependent ones, are preventable on condition that the risk factors, as the
      patient's age, functional capacity of eliminating organs (kidney, liver),
      associated diseases and simultaneous administration of drugs, are considered. In
      conclusion, the clinically significant drug interactions of antibiotics are
      pointed out, being of increasing importance especially in patients with multiple
      diseases and polypragmatic manner of treatment. (Tab. 2, Ref. 48.)

PMID- 12519002
TI  - The Tuskegee Legacy Project: history, preliminary scientific findings, and
      unanticipated societal benefits.
AB  - This article is intended to provide a relatively complete picture of how a pilot
      study--conceived and initiated within an NIDCR-funded RRCMOH--matured into a
      solid line of investigation within that center and "with legs" into a fully
      funded study within the next generation of NIDCR centers on this topic of health
      disparities, the Centers for Research to Reduce Oral Health Disparities. It
      highlights the natural opportunity that these centers provide for multicenter.
      cross-disciplinary research and for research career pipelining for college and
      dental school students; with a focus, in this case, on minority students.
      Futhermore, this series of events demonstrates the rich potential that these
      types of research centers have to contribute in ways that far exceed the
      scientific outcomes that form their core. In this instance, the NMOHRC played a
      central--and critical, if unanticipated--role in contributing to two events of
      national significance, namely the presidential apology to the African American
      community for the research abuses of the USPHS--Tuskegee syphilis study and the
      establishment of the National Center for Bioethics in Research and Health Care at
      Tuskegee University. Research Centers supported by the NIH are fully intended to
      create a vortex of scientific activity that goes well beyond the direct
      scientific aims of the studies initially funded within those centers. The maxim
      is that the whole should be greater than the sum of its initial constituent
      studies or parts. We believe that NMOHRC did indeed achieve that maxim--even
      extending "the whole" to include broad societal impact. well beyond the scope of
      important, but mere, scientific outcomes--all within the concept and appropriate
      functions of a scientific NIH-funded research center.

PMID- 12519003
TI  - Understanding health behavior and perceptions.
AB  - Oral health and general health status depend on a dynamic interplay of many
      factors, including the individual's personal characteristics, behaviors, and
      perceptions. There are differences and disparities among different racial and
      ethnic groups in terms of oral health status, and in the physical, socioeconomic,
      cultural, and political environment. Furthermore, response to the environment may
      vary among individuals and populations. Access to care and patient-provider
      interactions are key issues to consider. This article presents a conceptual model
      of the variable influences on behaviors and perceptions that determine oral
      health status in minority and other populations.

PMID- 12519004
TI  - Dental health status and indicators of treatment needs of four Hispanic subgroups
      in New York City.
AB  - This article presents the results of a study of four Hispanic subgroup residents
      of New York City. Utilizing National Institute of Dental and Craniofacial
      Research criteria and a specially designed survey instrument, the authors
      conducted oral examinations and interviews on 1,010 Hispanic adults. Results
      showed that the oral health status and the indicators of treatment needs differed
      among the subgroups. When conducting needs assessment and providing oral health
      care services for this population, differences among the subgroups must be
      considered.

PMID- 12519005
TI  - Dental caries prevalence among a sample of African American adults in New York
      City.
AB  - According to available limited epidemiology studies, the prevalence of oral
      disease is much greater in American minorities (Blacks, Hisoanics, Asians, Native
      Americans) than in the majority population. The purpose of this article is to
      describe the oral health status and current treatment needs of a group of African
      American (AA) adults in New York City. The convenience sample consisted of 951 AA
      adults (M = 662, F = 289) recruited through community- or faith-based
      institutions, and the in-house screening conducted by the Research Center for
      Minority Oral Health in dedicated dental clinics at the New York University
      College of Dentistry. The age of participants ranged from 18 to 64 years, (mean
      age 42, SD = 11.04). Calibrated examiners performed the clinical examinations
      utilizing National Institute of Dental and Craniofacial Research (NIDCR)
      diagnostic criteria. The DMFT, DMFS, DFS, and %D/DFS indices were obtained and
      results indicated the following. For the 18 to 34 age group (n = 246), the mean
      DMFT was 8.83, the mean DMFS was 21.36, the mean DFS was 12.10, and the mean
      %D/DFS was 30. For the 35 to 49 age group (n = 523), the mean DMFT was 14.03, the
      mean DMFS was 48.21, the mean DFS was 18.76, and the mean %D/DFS was 29. For the
      50 to 64 age group (n = 182), the mean DMFT was 15.38, the mean DMFS was 64.48,
      the mean DFS was 17.98, and the mean %D/DFS was 29. For all age groups, the
      findings indicated a high prevalence of dental decay and greater number of filled
      surfaces compared with the United States national surveys.

PMID- 12519006
TI  - Microbiological composition of whole saliva and caries experience in minority
      populations.
AB  - Microbiological factors in whole saliva, previously implicated in dental caries
      formation, were studied in four caries-positive adult ethnic groups: Asians,
      blacks, whites, and Hispanics. Whole saliva was collected from each patient and
      used for the enumeration of total cultivable microflora (T), streptococci, mutans
      streptococci (MS), and lactobacilli. In the female subgroup, statistically
      significant differences were found among the ethnic groups with regard to T in
      saliva. In the male subgroup, statistically significant differences were found
      among the ethnic groups with regard to MS in saliva. Statistically significant
      differences were also found among the ethnic groups in relation to caries score
      (DMFS), with the Hispanic group having the highest mean DMFS score; and among
      socioeconomic groups with regard to MS in saliva. Moreover, microbial composition
      (T and MS) of whole saliva and DMFS scores differed significantly (P < 0.05)
      among the ethnic groups studied.

PMID- 12519008
TI  - Destructive periodontal diseases in minority populations.
AB  - Disparities in the prevalence and severity of destructive periodontal diseases
      have been reported for American minority populations and have raised the
      following questions. Are differences in destructive periodontal disease
      prevalence and severity due to genetic or other confounding variables associated
      with ethnicity race? Do risk factors for destructive periodontal diseases differ
      among American minority populations or differ from the population at large?
      Answers to these questions will have profound impact on the direction of future
      research and the allocation of resources to address disparities in destructive
      periodontal diseases in American minority populations. Risk assessment studies
      that examined a set of clinical, demographic, immunologic, and microbiologic
      parameters of Asian Americans, African Americans, and Hispanic Americans resident
      in the greater New York City region suggest that occupational status, monitored
      as a surrogate variable for socioeconomic status, may be a more robust risk
      factor than ethnicity/race for destructive periodontal diseases in these
      populations.

PMID- 12519007
TI  - Characterization of maternal mutans streptococci transmission in an African
      American population.
AB  - In the current literature database, information on microbiological attributes to
      caries outcomes in African American populations is limited and scattered. Few
      reports have discussed MS infection and transmission from African American
      mothers to their children. During the past few years, the research group at the
      University of Alabama at Birmingham and the Jefferson County Pubic Health
      Department have done a series of extensive studies to systematically investigate
      the prevalence of MS colonization, the time of initial MS infection as defined as
      "the window of infectivity," the source of MS transmission as defined as "the
      fidelity of transmission, and the chemotherapeutic management of MS transmission
      and caries prevention. The objective of this report was to summarize the main
      significant findings generated during a period of 15 years of study. One
      limitation of the studies outlined in this article is that the research
      populations were predominately African American families. The inclusion of white
      and other minorities would make the conclusions more generalizable to the US
      population as a whole. Nevertheless, the information presented in this report can
      serve as baseline knowledge for future studies of caries etiology in African
      American and other ethnic populations.

PMID- 12519009
TI  - Preterm low birth weight and periodontal disease among African Americans.
AB  - African Americans consistently experience higher rates of preterm and low birth
      weight (LBW) deliveries than do whites. LBW and preterm infants are more likely
      to die before their first birthday and survivors may suffer from a number of
      health problems. Therefore, identification of modifiable risk factors for preterm
      deliveries and LBW has considerable public health significance. Pregnant women's
      poor periodontal healtlh is emerging as one such factor. Maternal clinical
      periodontal status and bacteriologic and immunologic profiles related to
      periodontal disease have been associateted with risk of fetal growth and preterm
      LBW, and periodontal treatment during pregnancy has reduced the incidence of
      preterm deliveries. This article reviews the literature on the above association
      and presents data from a previously published prospective study of predominantly
      African Americans to show that preterm LBW deliveries are associated with higher
      midtrimester maternal serum antibody levels against Porphyromonas gingivalis.

PMID- 12519010
TI  - Orofacial injury in underserved minority populations.
AB  - The translation of clinical and epidemiological research findings into cliniical
      practice in the management of orofacial injuries at an inner-city community
      promises a reduction in the incidence and severity of orofacial injuries. This
      article reports on the sociodemographic characteristics, economical impact,
      nature of injuries, and associated risk factors of mandible fractures sustained
      in the inner-city community treated at KDMC. An overwhelmingly high incidence of
      intentional/assaultive injuries were treated at KDMC that contribute to the
      escalating cost of medical care provided at the public county hospital. Knowledge
      of associated risk factors and nature of injuries is fundamental to the
      development of a sound screening and interventional program tailored to the high
      risk minority groups, to reduce the high burden of preventable orofacial injuries
      in this community. Multidisciplinary health professionals should recognize the
      relationship between alcohol and substance abuse and orofacial injuries and the
      subtle signs of domestic abuse. and should provide social support and counseling
      intervention to reduce risk of recurrent injuries in abused victims.

PMID- 12519011
TI  - Psychosocial sequelae and correlates of orofacial injury.
AB  - Orofacial injury is a condition that disproportionately affects disadvantaged
      minorities--particularly young men--with great personal and health care
      consequences. Beyond the overt physical injury, a large proportion of the
      presenting patients manifest acute psychological sequelae. Although many patients
      may recover, in a sizeable proportion the symptoms may persist for extended
      periods of time and prove to be an obstacle to rehabilitation and reintegration.
      Health care givers should pay equal attention to evolving psychological sequelae
      of facial injuries. Strategic questions and screening for risk indicators can
      help with timely posttrauma identification of individuals most vulnerable to the
      development of acute and chronic symptomatology.

PMID- 12519012
TI  - Clinical implications of the oral manifestations of HIV infection in children.
AB  - The authors hypothesized that patients infected with HIV at birth would be more
      vulnerable to oral diseases such as periodontal disease and caries because of
      their compromised immune system. As a result, they designed a 3-year,
      longitudinal, case-controlled study that examined HIV-infected children as
      compared with their normal noninfected household peers. Over 100 HIV-infected
      participants ages 2 to 15 years were examined at 6-month intervals; no
      differences were found with respect to caries or periodontal disease prevalence
      and incidence when the two groups were compared. Although the level of oral
      disease was similar in the two groups, both groups had more caries than the
      national norm. Thus, failure to use a control group would have led to the
      erroneous conclusion that children with HIV infection had a high level of caries.
      In addition, the authors discovered that tooth eruption was delayed in the HIV
      infected group, suggesting some developmental impediment. The HIV-infected group
      also showed more oral lesions that included candidiasis, linear gingival
      erythema, and medial rhomboid glossitis. Overall, oral lesions were not valid
      predictors of the serious consequences of AIDS. The authors speculated, however,
      that examinations at intervals more frequent than every 6 months might be
      required to determine whether oral lesions can predict frank AIDS and lowered CD4
      cell counts.

PMID- 12519013
TI  - The legacy of the regional research centers for minority oral health.
AB  - The Regional Research Centers for Minority Oral Health (RRCMOH) helped to
      redefine the research and education missions of the participating institutions,
      and placed new emphasis on early diagnosis, prevention, and conservative
      interventions in minority-related oral diseases, with an eye toward innovative,
      cost-effective solutions to long-neglected and underfunded areas of dental and
      craniofacial research, education, and health promotion programs. This article
      reviews the legacy of the RRCMOH.

PMID- 12519014
TI  - Interacting roles of myofibroblasts, apoptosis and fibrogenic growth factors in
      the pathogenesis of renal tubulo-interstitial fibrosis.
AB  - The interrelationship between myofibroblasts and fibrogenic growth factors in the
      pathogenesis of renal fibrosis is poorly defined. A temporal and spatial analysis
      of myofibroblasts, their proliferation and death, and presence of transforming
      growth factor-beta1 (TGF-beta1) and platelet-derived growth factor-B (PDGF-B) was
      carried out in an established rodent model in which chronic renal scarring and
      fibrosis occurs after healed renal papillary necrosis (RPN), similar to that seen
      with analgesic nephropathy. Treated and control groups (N = 6 and 4,
      respectively) were compared at 2, 4, 8 and 12 weeks. A positive relationship was
      found between presence of tubulo-interstitial myofibroblasts and development of
      fibrosis. Apoptotic myofibroblasts were identified in the interstitium and their
      incidence peaked 2 weeks after treatment. Levels of interstitial cell apoptosis
      and fibrosis were negatively correlated over time (r = -0.57, p < 0.01),
      suggesting that as apoptosis progressively failed to limit myofibroblast numbers,
      fibrosis increased. In comparison with the diminishing apoptosis in the
      interstitium, the tubular epithelium had progressively increasing levels of
      apoptosis over time, indicative of developing atrophy of nephrons. TGF-beta1
      protein expression had a close spatial and temporal association with fibrosis and
      myofibroblasts, whilst PDGF-B appeared to have a closer link with populations of
      other chronic inflammatory cells such as infiltrating lymphocytes. Peritubular
      myofibroblasts were often seen near apoptotic cells in the tubular epithelium,
      suggestive of a paracrine toxic effect of factor/s secreted by the
      myofibroblasts. In vitro, TGF-beta1 was found to be toxic to renal tubular
      epithelial cells. These findings suggest an interaction between myofibroblasts,
      their deletion by apoptosis, and the presence of the fibrogenic growth factor TGF
      beta1 in renal fibrosis, whereby apoptotic deletion of myofibroblasts could act
      as a controlling factor in progression of fibrosis.

PMID- 12519015
TI  - Secretion of basic fibroblast growth factor (FGF-2) by WEHI-3B myelomonocytic
      leukemia cells.
AB  - In order to investigate the role of Fibroblast Growth Factors in hematopoietic
      cells, we studied the expression of FGF-1, FGF-2, FGF-3, FGF-4, FGF-5 and FGF-6
      mRNAs both in murine myelomonocytic leukemia WEHI-3B and in a murine stromal cell
      line SR-4987. Secretion of FGF-2 in the cell culture supernatant was also
      studied. Expression of mRNA encoding for the above-mentioned FGFs was analyzed by
      RT-PCR. The production of FGF-2 in the conditioned media of WEHI-3B and SR-4987
      cell cultures was evaluated by techniques of affinity chromatography,
      chromatofocusing and immunoblotting. The biological activity of FGF-2 was checked
      on SR-4987 cells by a agar clonogenic assay. In both cell lines mRNA was found
      encoding for FGF-1, FGF-2 and FGF-6 and WEHI-3B cells express also mRNA for FGF-3
      (int-2) and FGF-4 (K-FGF/hst). Furthermore, supernatant from WEHI-3B cells was
      found to stimulate dramatically the agar clonogenicity of SR-4987 cells which
      have a very poor basal capacity for growth in agar. The clonogenic activity of
      WEHI-3B conditioned medium is due to FGF-2 secreted into cell culture supernatant
      whereas SR-4987 cells, although express FGF-2 mRNA, do not seem able to secrete
      this factor. The expression in myeloid leukemia cells of oncogene-related factors
      such as FGF-3, FGF-4 and FGF-6 together with the secretion of FGF-2 able to
      support a positive regulation of bone marrow stromal cells function suggest that
      FGFs may have an important role in sustaining the leukemogenic process and
      related disorders.

PMID- 12519016
TI  - Activation of the gene for the PDGF receptor beta1 (PDGFRbeta) in interleukin-3
      dependent myeloid cells by retroviral insertional mutagenesis: implications for
      the transforming potential of PDGFRbeta.
AB  - Retroviral insertional mutagenesis has proven to be a powerful tool to identify
      genetic lesions disrupting normal hematopoiesis. The gene encoding the beta
      receptor for platelet-derived growth factor (PDGFRbeta) was identified as a
      target of retroviral mutagenesis in mutants selected for interleukin-3 (IL3)
      independent growth. Expression of PDGFRbeta in the parental cells using a
      retroviral vector increased the frequency of factor-independent growth,
      confirming the significance of the retroviral integration site. Significantly,
      however, expression of the receptor did not induce IL3-independent growth in one
      step. In contrast, TEL-PDGFRbeta, the fusion protein generated by the t(5;12)
      translocation associated with chronic myelomonocytic leukemia, induced factor
      independent growth in all transductants, demonstrating that the TEL-PDGFRbeta
      fusion protein is a more potent mitogenic signal. Nevertheless PDGFRbeta
      overexpression is sufficient to give a selective advantage to IL3-dependent cells
      under adverse conditions, allowing the selection of secondary mutations that
      impart IL3-independent growth. These results underline the power of insertional
      mutagenesis to identify subtle but initiating mutations that synergize with other
      lesions in oncogenic transformation.

PMID- 12519017
TI  - Cytotoxicity of paclitaxel or cisplatin on carcinoma cell lines is not inhibited
      by leukemia inhibitory factor (LIF).
AB  - We have established a reliable, reproducible and objective growth assay to
      measure whether leukemia inhibitory factor (LIF) was able to protect tumour
      derived cell lines from toxic effects of the chemotherapy agents, cisplatin and
      paclitaxel. Using this assay, we demonstrated that LIF did not alter the
      cytotoxic action of these drugs, on a panel of seven cancer cell lines. This was
      not because of the inactivity of the LIF or because the cell lines did not
      express components of the LIF receptor. These findings suggest that the potential
      clinical use of LIF, as a neuroprotective agent, in conjunction with chemotherapy
      will not interfere with the anti-tumour treatment.

PMID- 12519019
TI  - The 7th International Conference on NGF and Related Molecules.

PMID- 12519018
TI  - Identification of activin A and follistatin in human milk.
AB  - Activin A is a dimeric protein member of the transforming growth factor-beta (TGF
      beta) family: it is synthesized by a variety of organs and follistatin is an
      activin-binding protein. A sensitive and specific assays for bioactive dimeric
      activin A and follistatin have recently allowed to measure these proteins in
      blood and other biological fluids, giving a new insights into their possible
      physiological role. Since human breast is able to produce activin A, the aim of
      the present study was to evaluate whether it and follistatin are measurable in
      breast milk of women during lactation. Concentrations of activin A and
      follistatin were measured in milk samples collected at 3, 5 and 30 days after
      delivery by using specific and sensitive two-site ELISAs. For the first time the
      presence of immunoreactive activin A and follistatin in human milk has been
      shown; no significant different concentration between the third and the fifth day
      after delivery was found. Furthermore, no difference of activin A and follistatin
      concentration between the whole and the skim milk or between spontaneous delivery
      and cesarean section was found. Milk activin A and follistatin concentrations
      after 1 month of lactation were significantly decreased (P < 0.01). Activin A and
      follistatin are present in human milk in high concentrations in the first week of
      lactation, while decrease after a month suggesting a possible role as growth
      factors in human milk.

PMID- 12519020
TI  - An oscillatory correlation model of visual motion analysis.
AB  - We describe and evaluate a model of motion perception based on the integration of
      information from two parallel pathways: a motion pathway and a luminance pathway.
      The motion pathway has two stages. The first stage measures and pools local
      motion across the input animation sequence and assigns reliability indices to
      these pooled measurements. The second stage groups locations on the basis of
      these measurements. In the luminance pathway, the input scene is segmented into
      regions on the basis of similarities in luminance. In a subsequent integration
      stage, motion and luminance segments are combined to obtain the final estimates
      of object motion. The neural network architecture we employ is based on LEGION
      (locally excitatory globally inhibitory oscillator networks), a scheme for
      feature binding and region labeling based on oscillatory correlation. Many
      aspects of the model are implemented at the neural network level, whereas others
      are implemented at a more abstract level. We apply this model to the computation
      of moving, uniformly illuminated, two-dimensional surfaces that are either opaque
      or transparent. Model performance replicates a number of distinctive features of
      human motion perception.

PMID- 12519021
TI  - Stereoillusory motion concomitant with lateral head movements.
AB  - Stationary objects in a stereogram can appear to move when viewed with lateral
      head movements. This illusory motion can be explained by the motion-distance
      invariance hypothesis, which states that illusory motion covaries with perceived
      depth in accordance with the geometric relationship between the position of the
      stereo stimuli and the head. We examined two predictions based on the hypothesis.
      In Experiment 1, illusory motion was studied while varying the magnitude of
      binocular disparity and the magnitude of lateral head movement, holding viewing
      distance constant. In Experiment 2, illusory motion was studied while varying
      binocular disparity and viewing distance, holding magnitude of head movement
      constant. Ancillary measures of perceived depth, perceived viewing distance, and
      perceived magnitude of lateral head movement were also obtained. The results from
      the two experiments show that the extent of illusory motion varies as a function
      of perceived depth, supporting the motion-distance invariance hypothesis. The
      results also show that the extent of illusory motion is close to that predicted
      from the geometry in crossed disparity conditions, whereas it is greater than the
      predicted motion in uncrossed disparity conditions. Furthermore, predictions
      based on perceptual variables were no more accurate than predictions based on
      geometry.

PMID- 12519022
TI  - The beholder's share in the perception of orientation of 2-D shapes.
AB  - A considerable amount of research demonstrates that people perceive cardinal
      orientations (horizontal and vertical) more accurately than other orientations;
      this is termed the oblique effect. We investigated the interaction of this effect
      with the degree of elongation of the stimulus. Our stimuli were ellipses with a
      wide range of aspect ratios, varying from a circle (aspect ratio = 1) to a line
      (aspect ratio = 123.5). The task was to set a probe line in the same orientation
      as the long axis of the ellipse. In our first experiment, we determined that
      performance is degraded as the aspect ratio decreases; furthermore, the bias and
      response variability are linearly related to a transformation of aspect ratio
      (roundness). We found significant individual differences; the results show high
      within-subjects correlations and low between-subjects correlations. In our second
      experiment, we had observers judge the orientation of circles randomly mixed in
      with ellipses of low aspect ratio. The observers demonstrated intrinsic
      preferences and generated reproducible distributions of orientation settings with
      idiosyncratic profiles. These distributions predict the influence on the response
      to ellipses with an aspect ratio higher than one and can be considered as the
      beholder's share in the perception of shape orientation.

PMID- 12519023
TI  - Gestalt grouping and common onset masking.
AB  - A four-dot mask that surrounds and is presented simultaneously with a briefly
      presented target will reduce a person's ability to identity that target if the
      mask persists beyond target offset and attention is divided (Enns & Di Lollo,
      1997, 2000). This masking effect, referred to as common onset masking, reflects
      reentrant processing in the visual system and can best be explained with a theory
      of object substitution (Di Lollo, Enns, & Rensink, 2000). In the present
      experiments, we investigated whether Gestalt grouping variables would influence
      the strength of common onset masking. The results indicated that (1) masking was
      impervious to grouping by form, similarity of color, position, luminance
      polarity, and common region and (2) masking increased with the number of elements
      in the masking display.

PMID- 12519025
TI  - A test of size-scaling and relative-size hypotheses for the moon illusion.
AB  - In two experiments participants reproduced the size of the moon in pictorial
      scenes under two conditions: when the scene element was normally oriented,
      producing a depth gradient like a floor, or when the scene element was inverted,
      producing a depth gradient like a ceiling. Target moons were located near to or
      far from the scene element. Consistent with size constancy scaling, the illusion
      reversed when the "floor" of a pictorial scene was inverted to represent a
      "ceiling." Relative size contrast predicted a reduction or increase in the
      illusion with no change in direction. The relation between pictorial and natural
      moon illusions is discussed.

PMID- 12519024
TI  - Encoding color and shape from different parts of an object in visual short-term
      memory.
AB  - Can we find an object-based encoding benefit in visual short-term memory (VSTM)
      when the features to be remembered are from different parts of an object? Using
      object parts defined by either figure-ground separation or negative minima of
      curvature, results from five experiments in which the visual change detection
      paradigm was used showed that the object-based encoding benefit in VSTM is
      modulated by how features are assigned to parts of an object: Features are best
      retained when the color and shape features to be remembered belong to the same
      part of an object. Although less well retained in comparison, features from
      different parts of an object are still better remembered than features from
      spatially separated objects. An object-based feature binding therefore exists
      even when the color and shape features to be remembered are from different parts
      of an object.

PMID- 12519026
TI  - The effect of response competition on functional hemispheric asymmetries for
      global/local processing.
AB  - It is widely assumed that the cerebral hemispheres differ in their capacity for
      processing the global and local levels of hierarchical stimuli. However,
      corresponding visual-field (VF) effects in response time studies did not show up
      under all circumstances. In the present article the role of response conflict
      between the levels for the occurrence of these effects is investigated. Three
      experiments with hierarchical letters are reported, in which the absolute and/or
      the relative interference between the stimulus levels was varied. It turned out
      that VF effects occurred only for conflicting stimuli and only when there was at
      least a certain amount of absolute interference, whereas variations of the
      relative interference had no effect in this respect. These results suggest that
      there is a qualitative relationship between interference and VF effects. A
      possible explanation is provided by the assumption that the hemispheres are
      functionally equivalent with respect to early stimulus representations, whereas
      they differ in their efficiency for integrating letter identity and stimulus
      level.

PMID- 12519027
TI  - Influences of hand posture and hand position on compatibility effects for up-down
      stimuli mapped to left-right responses: evidence for a hand referent hypothesis.
AB  - Unimanual left-right responses to up-down stimuli show a stimulus-response
      compatibility (SRC) effect for which the preferred mapping varies as a function
      of response eccentricity. Responses made in the right hemispace and, to a lesser
      extent, at a midline position, are faster with the up-right/down-left mapping
      than with the up-left/down-right mapping, but responses made in the left
      hemispace are faster with the up-left/down-right mapping. Also, for responses at
      the midline position, the preferred mapping switches when the hand is placed in a
      supine posture instead of the more usual prone posture. The response eccentricity
      effect can be explained in terms of correspondence of asymmetrically coded
      stimulus and response features, but it is not obvious whether the hand posture
      effect can be explained in a similar manner. The present study tested the
      implications of a hypothesis that the body of the hand provides a frame of
      reference with respect to which the response switch is coded as left or right. As
      was predicted by this hand referent hypothesis, Experiment 1 showed that the
      influence of hand posture (prone and supine) on orthogonal SRC was additive with
      that of response location. In Experiment 2, the location of the switch relative
      to the hand was varied by having subjects use either a normal grip in which the
      switch was held between the thumb and the index finger or a grip in which it was
      held between the little and the ring fingers. The magnitudes of the mapping
      preferences varied as a function of the grip and hand posture in a manner
      consistent with the hand referent hypothesis.

PMID- 12519028
TI  - Perception without awareness: further evidence from a Stroop priming task.
AB  - In the present research, we examined the influence of prime-target stimulus onset
      asynchrony (SOA) on Stroop-priming effects from masked words. Participants
      indicated the color of a central target, which was preceded by a 33-msec prime
      word followed either immediately or after a variable delay by a pattern mask. The
      prime word was incongruent or congruent with the target color on 75% and 25% of
      the trials, respectively. The words followed by an immediate mask produced
      reliable Stroop interference at SOAs of 300 and 400 msec but not at SOAs of 500
      and 700 msec. The words followed by a delayed mask produced a reversed (i.e.,
      facilitatory) Stroop effect, which reached significance at an SOA of 400 msec or
      longer, but never at the shorter 300-msec SOA. Such an differential time course
      of both types of Stroop priming effects provides further evidence for the
      existence of qualitative differences between conscious and nonconscious
      perceptual processes.

PMID- 12519029
TI  - Hearing speech against spatially separate competing speech versus competing
      noise.
AB  - Listeners had the task of following a target speech signal heard against two
      competitors either located at the same spatial position as the target or
      displaced symmetrically to locations flanking it. When speech was the competitor,
      there was a significantly higher separation effect (maintained intelligibility
      with reduced target sound level), as compared with either steady-state or
      fluctuating noises. Increasing the extent of spatial separation slightly
      increased the effect, and a substantial contribution of interaural time
      differences was observed. When same- and opposite-sex voices were used, a
      hypothesis that the similarity between target and competing speech would explain
      the role for spatial separation was partly supported. High- and low-pass
      filtering showed that both parts of an acoustically similar competing signal
      contribute to the phenomenon. We conclude that, in parsing the auditory array,
      attention to spatial cues is heightened when the components of the array are
      confusable on other acoustic grounds.

PMID- 12519030
TI  - Recognition of notated melodies by possessors and nonpossessors of absolute
      pitch.
AB  - Musically trained listeners compared a notated melody presented visually and a
      comparison melody presented auditorily, and judged whether they were exactly the
      same or not, with respect to relative pitch. Listeners who had absolute pitch
      showed the poorest performance for melodies transposed to different pitch levels
      from the notated melodies, whereas they exhibited the highest performance for
      untransposed melodies. By comparison, the performance of melody recognition by
      listeners who did not have absolute pitch was not influenced by the actual pitch
      level at which melodies were played. These results suggest that absolute-pitch
      listeners tend to rely on absolute pitch even in recognizing transposed melodies,
      for which the absolute-pitch strategy is not useful.

PMID- 12519031
TI  - Leading, but not trailing, primes influence temporal order perception: further
      evidence for an attentional account of perceptual latency priming.
AB  - Presenting a masked prime leading a target influences the perceived onset of the
      masking target (perceptual latency priming; Scharlau & Neumann, in press). This
      priming effect is explained by the asynchronous updating model (Neumann, 1982;
      Scharlau & Neumann, in press): The prime initiates attentional allocation toward
      its location, which renders a trailing target at the same place consciously
      available earlier. In three experiments, this perceptual latency priming by
      leading primes was examined jointly with the effects of trailing primes in order
      to compare the explanation of the asynchronous updating model with the onset
      averaging and the P-center hypotheses. Experiment 1 showed that an attended, as
      well as an unattended, prime leads to perceptual latency priming. In addition, a
      large effect of trailing primes on the onset of a target was found. As Experiment
      2 demonstrated, this effect is quite robust, although smaller than that of a
      leading prime. In Experiment 3, masked primes were used. Under these conditions,
      no influence of trailing primes could be found, whereas perceptual latency
      priming persisted. Thus, a nonattentional explanation for the effect of trailing
      primes seems likely.

PMID- 12519032
TI  - Determining whether attentional control settings are inclusive or exclusive.
AB  - The aim of the present study was to determine whether attentional control
      settings operate with an inclusive rule (orient attention to stimuli that share a
      task-relevant feature with the target) or an exclusive rule (do not orient
      attention to stimuli that do not share a task-relevant feature with the target).
      All three experiments used a variation of the Folk and Remington (e.g., Folk,
      Remington, & Johnston, 1992) paradigm. In Experiment 1, cuing effects were found
      for combination cues (cues containing an onset feature and a color feature) with
      both onset and color targets. Experiment 2, using a delay between cue and target,
      revealed inhibition of return (IOR) for combination cues with onset and color
      targets. Unexpectedly, IOR was also found for onset cues with color targets, and
      this finding was confirmed in Experiment 3. These findings indicate that
      attentional control settings use an inclusive rule. Moreover, the presence of IOR
      with onset cues and color targets suggests that onset cues may automatically
      capture attention, but attention control settings allow for rapid disengagement
      when the onset cue does not contain a task-relevant feature.

PMID- 12519034
TI  - EUROGIN 2003 Conference. Facts, figures and impact. Paris, Cite des Sciences-
      April 13-16, 2003.

PMID- 12519033
TI  - Laudation. Professor Antonio Onnis.

PMID- 12519035
TI  - Current attitudes toward hormone replacement therapy (HRT) prescribed during
      menopause.

PMID- 12519036
TI  - Clinical trial comparing the activity and efficacy of ibuprofen
      isobutanolammonium vs Benzydamine hydrochloride, applied as vaginal irrigations,
      in patients with vaginitis.
AB  - This study was conducted on 30 female patients (average age: 40.5 +/- 11 years,
      age range 19-65), affected by vulval and/or vaginal phlogosis with a prevalence
      of uterine fibromyomatosis and metrorrhagia of a varied nature. Sixteen patients
      were affected with vulvitis and 14 with vulvovaginitis. Fifteen patients were
      assigned to the treatment with Ibuprofen isobutanolammonium and 15 to the
      treatment with Benzydamine hydrochloride. Both the subjective symptoms (burning
      and itching) and the objective symptoms (erythema, oedema, exudation) showed a
      marked reduction as early as the third day of treatment and the comparison
      between the score at the start of treatment and on day three of the treatment was
      highly significant in both study groups (p < 0.01). This improvement was,
      however, more marked in the group of patients treated with ibuprofen
      isobutanolammonium, where a more rapid reduction of both the subjective and
      objective symptoms was observed on the third day. This trend, although not as
      marked as on the third day, was confirmed at the end of the study, on the seventh
      day.

PMID- 12519037
TI  - Clinical study on collagen and stress urinary incontinence.
AB  - OBJECTIVE: To investigate the histological characteristics in uterine ligaments
      of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); to detect
      the alteration of collagen ultrastructure in uterine ligaments that contribute to
      SUI and POP; to study the relationship between collagen alteration and SUI and
      POP. METHODS: The cardinal ligament (Car lig.) and uterosacral ligaments (U-S
      lig.) samples were obtained from 73 subjects suffering from SUI, or normal
      controls who underwent hysterectomy. Collagen ultrastructure was examined with
      transmission electron microscopy (TEM). RESULTS: 1) The smooth muscle fascicles
      in the patients with SUI and POP were thinner. Arrangement of smooth muscle
      fascicles was in disorder. 2) The collagen constituting the ligaments was active
      in metabolism. The mean collagen fibril diameters in the SUI and POP groups were
      about 25% larger than that in the control groups (p < or = 0.01). 3) Histological
      characteristics of the Car lig. and the U-S lig. were similar. CONCLUSIONS: 1)
      The Car lig. and U-S lig. are homologous. Abnormalities in arrangement of smooth
      muscles and the collagen ultrastructure were obviously seen in SUI and POP 2) The
      collagen fibril diameter in the SUI and POP subgroups was significantly larger
      than that in the control groups. Those ligaments are probably less elastic and
      more likely to break. Predominance of collagen degradation during tissue repair
      may contribute to POP and SUI.

PMID- 12519038
TI  - Granulomatous chemical peritonitis on the ileocecum after laparoscopic surgery of
      an ovarian mature cystic teratoma: case report.
AB  - The possibility of granulomatous peritonitis should be considered when
      laparoscopy is necessary in patients with ovarian mature cystic teratoma.

PMID- 12519039
TI  - Postmenopausal osteoporosis and celiac disease.
AB  - Individualizing risk factors is the most important tool to prevent late
      consequences of menopause. Celiac disease is a predisposing condition not very
      considered for some postmenopausal diseases, such as postmenopausal osteoporosis.
      In this review the authors examine climacteric conditions that could be
      heightened by a celiac status especially if disregarded and untreated.

PMID- 12519040
TI  - Ectopic pregnancy without therapy despite previous failure with in vitro
      fertilization and a male partner with an extremely low hypoosmotic swelling test
      score: case report.
AB  - PURPOSE: To record an ectopic pregnancy achieved through natural intercourse
      despite previous implantation failure following in vitro fertilization-embryo
      transfer (IVF-ET) with a male partner who had an extremely low hypoosmotic
      swelling test (HOST) score. METHODS: A hypoosmotic swelling test was performed
      for the first time on the semen of a male partner who was advised previously that
      his sperm specimen was perfectly normal. RESULTS: The standard semen parameters
      except normal morphology with strict criteria were normal. The HOST score was
      33%. CONCLUSIONS: The HOST score of 33% was the lowest level recorded in anyone
      achieving a pregnancy. The fact that it resulted in an ectopic pregnancy in a
      woman with apparently normal tubes and failure to achieve an intrauterine
      pregnancy despite transfer of 13 embryos with good morphology may suggest that
      the low HOST score inhibits the blastocyst from implanting in the uterus rather
      than from failure to develop a blastocyst from a multi-cell embryo.

PMID- 12519041
TI  - Biochemical markers of bone turnover in girls with secondary amenorrhoea.
AB  - Our aim has been to evaluate the influence of menstrual disturbances of the
      secondary amenorrhoea type on the metabolism of bone tissue. We pursued this goal
      by determining selected biochemical markers of bone metabolism. Alkaline
      phosphatase and osteocalcin were used as indices of bone remodelling.
      Deoxypiridinoline was used as an index of bone tissue resorption.

PMID- 12519042
TI  - An unusual case of transitional obstructive acute renal failure during labor.
AB  - An unusual case of transitional obstructive acute renal failure during labor
      which resolved after delivery is described.

PMID- 12519043
TI  - Human fetal adrenal transplant: a possible role in relieving intractable pain in
      advanced rheumatoid arthritis.
AB  - BACKGROUND: The art of transplant surgery has gone a long way in establishing
      itself as an important discipline in medicine with the support of molecular
      biology, immunology, biochemistry, etc., as the ultimate treatment for the
      restoration of function of a failing organ. With the progressive increase in the
      life expectancy of human beings, there is an increasing discrepancy in the demand
      and supply of organ grafts. A less efficient alternative could be synthetic or
      mechanical grafts. Nucleated cell therapy, that is, cellular transplant, is a
      promising new area of study with its proven efficacy in neuro-degenerative
      disorders, hematopoietic disorders, diabetes and trauma-induced tissue loss, to
      name a few. Human fetal cell/tissue with its intrinsic hypo-antigenic advantage
      (up to 20 weeks of study), could be an interesting area of cellular/tissue
      transplant. Our research group has earlier reported on the safe use of umbilical
      cord whole blood and the successful transplant of a human fetal lung, heart,
      pancreas, liver, thymus, in an artificially prepared vascular subcutaneous
      axillary fold in which there was no feature of hyper-acute, acute or chronic
      rejection of the graft in HLA- and sex-randomized adult recipients, without
      concomitant immunosuppressives or radiation of the host to potentiate the
      survival of the fetal graft (within 20 weeks of gestation) within the lowest
      observation period of one month. The present study was aimed at examining the
      role of developing fetal adrenal transplants for patients with rheumatoid
      arthritis and severe pain due to involvement of inflammatory and neuropathic
      components. MATERIALS AND METHOD: Ten cases were enrolled in the present study
      after thorough informed consent and approval by the ethical committee of the
      institute. The age of the patients varied from 50 to 76 years and the group was
      comprised of three males and seven females. The age of the adrenal grafts varied
      from 16 to 20 weeks and these were collected from mothers admitted for
      hysterotomy and ligation. These long-standing rheumatoid patients (suffering for
      five to 15 years), presented with at least four of the seven 1987 revised
      criteria of the American College of Rheumatology for diagnosis of rheumatoid
      arthritis. A 2.5 cm long and 2 cm deep tissue space was dissected and prepared in
      each transplant recipient at the axilla using diathermy and knife after
      infiltrating the site with one percent lignocaine solution. The tissue collected
      from the consenting mother undergoing hysterotomy and ligation was inserted into
      this site, and the site was closed with 00 atraumatic vicryl. All necessary pre-
      and postoperative surgical precautions were taken to prevent infections.
      Sequential total count and differential count of leucocytes were undertaken to
      analyze the impact of the transplant on the host. After one month, a part of the
      transplanted fetal tissue was recovered for histological staining to examine
      whether there was any graft versus host reaction. RESULTS AND ANALYSIS: All ten
      patients tolerated the transplant procedure well. There was no fever, intractable
      pain or any other specific serious side-effect which could justify the removal of
      the transplant before one month. There was no discharge from the incision site
      and the healing of the scar was by and large normal. There was no unusual
      leucocytosis, lymphocytosis and the retrieved graft tissue did not suggest
      transplant rejection. However, there was definite pain relief, reduction in
      swelling and improvement of mobility of varying degree in a majority of the
      patients which was perceivable from the 15th day onwards. There was also a sense
      of well being (in 80%) and a gain in weight of three pounds or more (in 70%)
      among the fetal transplant recipients. DISCUSSION AND CONCLUSION: To understand
      the underlying mechanism, in case of pregnancy immunotolerance, we are of the
      opinion that emphasis should be placed on the role of non-specific and non
      cytopathic blocking antibodies produced during pregnancy. The hypo-antigenicity
      of the developing human fetal system may possibly contribute to the production of
      this blocking antibody during pregnancy, and thus may play a role in the lack of
      recognition by the host's HLA system. This behaviour of the developing human
      fetal tissue provides some advantages over adult tissue for fetal cell/tissue
      transplantation purposes. The relief of pain, inflammation and restoration of
      mobility may be due to the effect of the transplanted adrenal graft, with the
      medullary component contributing to endorphin-like substance liberation and the
      cortical component contributing to glucocorticoid synthesis.

PMID- 12519044
TI  - Disturbances of humour in postpartum: our experience.
AB  - The study was conducted on 64 women who were to give birth. The average age
      ranged from 31-44 years and the instruments for evaluation consisted of: 1)
      Individual and psychological questionnaires; 2) Italian version of the Short Form
      Health Survey Questionnaire (SF-36); 3) Sheehan Disability Scale; 4) Zung self
      rating depression scale. Of the women included in the study 27.7% found their
      humour worsened during their last pregnancy, while 19.15% said that their humour
      worsened after the birth. In these patients we frequently found obstetric and/or
      puerperal pathologies. There was also a strong correlation with the premenstrual
      syndrome and with hyperemesis in the first trimester. On the contrary, there was
      no correlation with familiarity and socio-demographic characteristics. The data
      allow us to conclude that any pregnant woman can develop medium or strong
      symptoms of depression thus calling for great attention to be paid to the
      psychological dynamics of birth.

PMID- 12519045
TI  - The effect of delivery on umbilical arterial cord blood gases and lipid
      peroxides: comparison of vaginal delivery and cesarean section.
AB  - Umbilical arterial blood gas analysis is the most objective method to assess
      fetal well being at birth, is the gold standard assessment of uteroplacental
      function and fetal oxygenation/acid-base status at birth, and it excludes the
      diagnosis of birth asphyxia in approximately 80% of depressed newborns at term.
      This study was designed to determine the effect of the type of delivery on
      umbilical cord blood gases and on free radical activity together with
      antioxidation in the fetus. Ninety-six pregnant women between 37 and 42 weeks of
      gestation were included to the study and randomly assigned to the one of three
      groups: Group 1 (n = 40) were vaginally delivered, Group 2 (n = 26) had cesarean
      section with epidural anaesthesia, and Group 3 (n = 30) had cesarean section
      under general anaesthesia. Umbilical artery blood gas analysis was performed just
      after the delivery of the fetus together with melondealdehyde and glutathione.
      The umbilical arterial PO2 was found to be higher in Group 3, and malondealdehyde
      and glutathione levels were lower in newborns of Group 2. It can be concluded
      that cesarean section with epidural anaesthesia is safer when lipid peroxides are
      concerned.

PMID- 12519046
TI  - Ruptured heterotopic pregnancy: a report of unusual acute abdominal syndrome in
      two cases.
AB  - A heterotopic pregnancy is in effect a multiple pregnancy with one or more
      intrauterine pregnancies coexisting with an ectopic pregnancy. Prompt diagnosis,
      rapid fluid and blood resuscitation, heart-sparing anesthesia and gentle,
      expeditious surgery collectively contribute to a favorable outcome for the mother
      and fetus in patients with a ruptured tubal pregnancy. In this report we present
      two cases of heterotopic pregnancies with ruptured tubal components; one
      spontaneous and the other one after clomiphene citrate treatment. Explorative
      laparotomy and salpingectomy were performed in both patients. After surgery, the
      intrauterine pregnancies were not damaged, and were still healthy on progression.

PMID- 12519047
TI  - Early diagnosed intramural ectopic pregnancy associated with adenomyosis: report
      of an unusual case.
AB  - Intramural pregnancy is the rarest type of ectopic pregnancy and almost always is
      diagnosed intraoperatively. It constitutes less than 1% of ectopic pregnancies
      and the world literature contains only 33 cases. We present an additional case of
      an uncomplicated intramural pregnancy in a patient with extensive adenomyosis,
      which is the earliest preoperatively diagnosed (sixth week of gestation) case in
      the literature.

PMID- 12519048
TI  - Behcet's disease: part of the differential diagnosis of the ulcerative vulva.
AB  - BACKGROUND: Behcet's disease is a heterogeneous pathological entity of unknown
      etiology, most of the time affecting many organs concurrently. CASES: We report
      two cases of women who presented with ulcerations of the vulvar area as the first
      symptom, highlighting the diagnostic difficulties that were encountered until the
      diagnosis of Behcet's disease was confirmed. CONCLUSION: Behcet's disease should
      be kept in mind as a part of the differential diagnosis of vulvar ulcers.

PMID- 12519049
TI  - The effects of add-back therapy with tibolone on myoma uteri.
AB  - In this prospective, randomized, double-blind study, we evaluated the effects of
      tibolone therapy in association with preoperative gonadotropin releasing hormone
      agonist (GnRHa) therapy on the reduction of myoma volume. Twenty patients with
      myoma uteri were divided into two groups. Group I was given monthly triptoreline
      (3.75 mg every 28 days IM) treatment for six months. As for group II, tibolone
      was added on to this treatment. For all of the patients, physical examinations,
      pelvic ultrasonography, and hormone analyses were carried out and the myoma
      volume was measured by ultrasonography. The patients were called every month and
      physical examination, ultrasonography and hormone analyses were repeated. Side
      effects were recorded. The SPSS/PC 6.0 program was used for statistical analysis.
      Statistical significance was defined as a p < 0.05. The results are expressed as
      means +/- SD. While the average volume of myoma was 72.97 +/- 68.5 cm3 in group
      I, 78.83 +/- 74.1 cm3 in group II before treatment; it was reduced to 29.91 +/-
      27.8 cm3 in group I at the end of six months of treatment. Reductions of 59.6% in
      group I and 63.9% in group II were determined, however the difference was not
      statistically significant (p > 0.05). At the beginning the level of serum
      estradiol was 65.4 +/- 22.3 pg/ml in group I which decreased to 37.2 +/- 4.2
      pg/ml by the end of the first month. Amenorrhea occurred in six patients after
      the second injection and four patients after the third injection in group I.
      Whereas the level of estradiol was 60.9 +/- 19.5 pg/ml in group II at the
      beginning, it was reduced to 40.5 +/- 6.2 pg/ml by the end of the first month.
      Amenorrhea occurred in four patients after the second injection and four patients
      after the third injection in group II. In group I the patients had the problem of
      flushing (80%), vaginal dryness (50%), and night sweats (30%). In group II these
      rates were 30%, 20%, and 20%, respectively. Triptoreline is a GnRHa which has
      been found to be effective in reducing myoma volume, but this effect could not be
      deactivated with tibolone. However, a decrease was observed in the side-effects
      resulting from hypoestrogenism.

PMID- 12519050
TI  - Amalgam, autism, and the beauty of Holland.

PMID- 12519051
TI  - Treatment of crown fractures with exposed pulps.
AB  - Traumatic injuries are a common cause of pulpal damage in anterior teeth. Crown
      fractures with exposed pulps represent 18 percent to 20 percent of the traumatic
      injuries that involve the teeth. This clinical study comprised 36 patients, who
      were referred for 40 crown fractures with pulp exposures. There were 39 maxillary
      incisors and one mandibular incisor. The partial pulpotomy (Cvek's technique)
      consists of amputating exposed pulp tissue to a depth of 1 to 2 mm below the
      point of pulp exposure. After partial pulpotomy, the pulpal wound is covered with
      calcium hydroxide; and the cavity is sealed with glass ionomer cement or a
      composite crown. Clinical and radiographic assessment of the hard-tissue barrier
      was done after three months. Patients were monitored for periods ranging from one
      to 12 years. The purpose of this clinical report was to evaluate Cvek's technique
      in the management of coronal fractures with pulp exposures and the long-term
      outcome of the partial pulpotomy in immature and mature teeth. In virtually all
      of the cases, this treatment was successful. Careful partial pulpotomy remains a
      prudent treatment choice with proper case selection.

PMID- 12519052
TI  - Dental care for individuals with developmental disabilities is expensive, but
      needed.
AB  - More than $35 billion in additional lifetime costs will be expended for all
      children in the United States born with mental retardation in 1998 alone. The
      figure is $4.7 billion for California children. These numbers include neither the
      costs for individuals with other developmental disabilities, nor the costs for
      dental services. Despite the findings that individuals with mental retardation
      have more untreated dental needs than individuals in the general population, most
      dental students and many practitioners have limited experience in providing care
      for patients with special needs. The significant additional general costs for the
      care of people with mental retardation and other developmental disabilities are a
      reality, but the dental profession must not lose sight of the need for its
      members to provide services for these individuals.

PMID- 12519053
TI  - Application of problem-based learning to clinical dental education.
AB  - Problem-based learning provides a mechanism for learning in a manner that most
      closely simulates the future practice environment. PBL was initiated in medical
      education in the 1960s, and two-thirds of U.S. medical schools use PBL in their
      programs. The University of Southern California School of Dentistry has moved to
      the PBL model to give its dental students the knowledge base required to meet
      accreditation standards and to prepare them to be beginning general
      practitioners. This article explains how USC uses PBL in its dental curriculum.

PMID- 12519054
TI  - Women dentists: the origins.
AB  - The pioneer women in dentistry are worthy of recognition and admiration. They
      broke the traditional barriers for their sex and set the standards for those who
      followed in their path as dental professionals. As medicine has its Elizabeth
      Blackwell, nursing its Florence Nightingale, so dentistry has its Lucy Taylor
      Hobbs and Henriette Hirschfeld. In 1884, Lucy Hobbs wrote: "People were amazed
      when they learned that a young girl had so far forgotten her womanhood as to want
      to study dentistry." Today, women represent almost 50 percent of the dental
      students in some dental schools. It is projected that by the year 2020, 20
      percent of all dental practitioners in the United States will be women. This
      article details a timeline of women's place in dental history by highlighting
      prominent women dentists and various opinions on women in dentistry.

PMID- 12519055
TI  - Monkeying with medical scheduling.

PMID- 12519056
TI  - Design, synthesis, and biological evaluation of fluoroneplanocin A as the novel
      mechanism-based inhibitor of S-adenosylhomocysteine hydrolase.
AB  - Fluoroneplanocin A (12) was designed as a novel mechanism-based inhibitor of S
      adenosylhomocysteine hydrolase (SAH) and efficiently synthesized via an
      electrophilic vinyl fluorination reaction (n-BuLi, N-fluorobenzenesulfonimide at 
      78 degrees C). Fluoroneplanocin A exhibited 2-fold more potent SAH inhibitory
      activity than the parent neplanocin A. A new mechanism of irreversible inhibition
      discovered in this work might provide new alternatives in the design of a
      different class of antiviral agents operating via SAH inhibition.

PMID- 12519057
TI  - 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective
      metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.
AB  - 2-Methyl-6-(phenylethynyl)pyridine (3), a potent noncompetitive mGlu5 receptor
      antagonist widely used to characterize the pharmacology of mGlu5 receptors,
      suffers from a number of shortcomings as a therapeutic agent, including off
      target activity and poor aqueous solubility. Seeking to improve the properties of
      3 led to the synthesis of compound 9, a highly selective mGlu5 receptor
      antagonist that is 5-fold more potent than 3 in the rat fear-potentiated startle
      model of anxiety.

PMID- 12519058
TI  - Potential tumor-selective nitroimidazolylmethyluracil prodrug derivatives:
      inhibitors of the angiogenic enzyme thymidine phosphorylase.
AB  - Thymidine phosphorylase (TP) is an angiogenic growth factor and a target for
      anticancer drug design. Molecular modeling suggested that 2'
      aminoimidazolylmethyluracils would be potent inhibitors of TP. The novel 5-halo-2
      aminoimidazolylmethyluracils (4b/4c) were very potent inhibitors of E. coli TP
      (IC50 approximately 20 nM). Contrastingly, the corresponding 2'
      nitroimidazolylmethyluracil (as bioreductively activated) prodrugs (3b/3c) were
      1000-fold less active (IC50 22-24 microM). This approach may be used to
      selectively deliver TP inhibitors into hypoxic regions of solid tumors where TP
      is overexpressed.

PMID- 12519059
TI  - Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors.
AB  - Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1)
      inhibitors have been synthesized. Several compounds were found to be powerful
      chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines.
      In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD+
      depletion and ADP-ribose polymer formation caused by chemically induced DNA
      damage.

PMID- 12519060
TI  - Competitive antagonism of AMPA receptors by ligands of different classes: crystal
      structure of ATPO bound to the GluR2 ligand-binding core, in comparison with
      DNQX.
AB  - Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion
      channels that are essential for mediating fast synaptic transmission in the
      central nervous system. This study presents a high-resolution X-ray structure of
      the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4
      isoxazolyl]propionic acid (ATPO) in complex with the ligand-binding core of the
      receptor. Comparison with the only previous structure of the ligand-binding core
      in complex with an antagonist, 6,7-dinitro-2,3-quinoxalinedione (DNQX)
      (Armstrong, N.; Gouaux, E. Neuron 2000, 28, 165-181), reveals that ATPO and DNQX
      stabilize an open form of the ligand-binding core by different sets of
      interactions. Computational techniques are used to quantify the differences
      between these two ligands and to map the binding site. The isoxazole moiety of
      ATPO acts primarily as a spacer, and other scaffolds could potentially be used.
      Whereas agonists induce substantial domain closures compared to the apo
      structure, ATPO only induces minor conformational changes. These results are
      consistent with the hypothesis that domain closure is related to receptor
      activation. To facilitate the design of novel AMPA receptor antagonists, we
      present a modified model of the binding site that includes key residues involved
      in ligand recognition.

PMID- 12519061
TI  - Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in
      complex with CDK2, enzyme selectivity, and cellular effects.
AB  - Cyclin-dependent kinases (CDKs) regulate the cell cycle, apoptosis, neuronal
      functions, transcription, and exocytosis. The observation of CDK deregulations in
      various pathological situations suggests that CDK inhibitors may have a
      therapeutic value. In this article, we report on the identification of 6
      phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) as a novel potent CDK inhibitory
      scaffold. A selectivity study performed on 26 kinases shows that aloisine A is
      highly selective for CDK1/cyclin B, CDK2/cyclin A-E, CDK5/p25, and GSK-3
      alpha/beta; the two latter enzymes have been implicated in Alzheimer's disease.
      Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal
      structure, demonstrate that aloisines act by competitive inhibition of ATP
      binding to the catalytic subunit of the kinase. As observed with all inhibitors
      reported so far, aloisine interacts with the ATP-binding pocket through two
      hydrogen bonds with backbone nitrogen and oxygen atoms of Leu 83. Aloisine
      inhibits cell proliferation by arresting cells in both G1 and G2.

PMID- 12519062
TI  - Structure-activity relationship of imidazo[1,2-a]pyridines as ligands for
      detecting beta-amyloid plaques in the brain.
AB  - A series of novel beta-amyloid (A beta) aggregate-specific ligands, 2-(4'
      dimethylaminophenyl)-6-iodoimidazo[1,2-a]pyridine, 16(IMPY), and its related
      derivatives were prepared. An in vitro binding study with preformed A beta
      aggregates showed that 16(IMPY) and its bromo derivative competed with binding of
      2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [125I]7(TZDM), a known ligand for
      A beta aggregates, with high binding affinities (K(i) = 15 and 10 nM,
      respectively). In vitro autoradiography of brain sections of a transgenic mouse
      (Tg2576) with [125I]16(IMPY) displayed high selective binding to amyloid-like
      structures, comparable to that observed by staining with thioflavin-S visualized
      under fluorescence. In vivo biodistribution after an intravenous injection of
      [125I]16(IMPY) in normal mice showed a high initial brain uptake and fast
      washout, indicating a low background activity associated with this iodinated
      ligand. Taken together, the data suggests that [123I]16(IMPY) may be useful for
      imaging A beta aggregates in patients with Alzheimer's disease.

PMID- 12519063
TI  - Macrocyclization in the design of Grb2 SH2 domain-binding ligands exhibiting high
      potency in whole-cell systems.
AB  - While most SH2 domains bind phosphotyrosyl (pTyr) containing peptides in extended
      fashion, the growth factor receptor-bound protein 2 (Grb2) SH2 domain
      preferentially binds ligands in bend conformations. Accordingly, incorporation of
      bend-inducing functionality into synthetic ligands could potentially enhance
      their affinity for this SH2 domain. A macrocyclic tripeptide mimetic that
      contains a simplified pTyr surrogate lacking an alpha-nitrogen has recently been
      shown to exhibit high Grb2 SH2 domain-binding affinity in extracellular ELISA
      based assays. However, the same compound is largely ineffective in whole-cell
      assays. It is known that acidic functionality originating from the alpha-nitrogen
      of pTyr residues or from the alpha-position of P0 pTyr mimetics not only
      increases binding affinity of peptides to Grb2 SH2 domains in extracellular
      assays but also enhances potency in cell-based systems. Such functionality is
      absent from the previously reported macrocycle. Therefore, the current study was
      undertaken to examine the effects of introducing carboxylic functionality at the
      pTyr mimetic alpha-position of macrocyclic ligands. It was found that such a
      modification not only enhanced Grb2 SH2 domain binding in extracellular assays
      but also conferred high efficacy in whole-cell systems. The most potent compound
      of the current study exhibited an IC(50) value of 0.002 microM in an
      extracellular ELISA-based assay, and in MDA-MB-453 cells, it both inhibited the
      association of Grb2 with p185(erbB-2) and exhibited antimitogenic effects with
      submicromolar IC50 values.

PMID- 12519064
TI  - Novel hexahydrospiro[piperidine-4,1'-pyrrolo[3,4-c]pyrroles]: highly selective
      small-molecule nociceptin/orphanin FQ receptor agonists.
AB  - Novel hexahydrospiro[piperidine-4,1'-pyrrolo[3,4-c]pyrroles that act as potent
      and selective orphanin FQ/nociceptin (N/OFQ) receptor (NOP) agonists were
      identified. The best compound, (+)-5a, potently inhibited 3H-N/OFQ binding to the
      NOP receptor (K(i) = 0.49 nM) but was >1000-fold less potent in binding to MOP,
      KOP, and DOP opiate receptors. Further, (+)-5a potently stimulated GTP gamma S
      binding to NOP membranes (EC50 = 65 nM) and inhibited forskolin-mediated cAMP
      accumulation in NOP-expressing cells (EC50 = 9.1 nM) with a potency comparable to
      that of the natural peptide agonist N/OFQ. These results indicate that (+)-5a is
      a highly selective and potent small-molecule full agonist of the NOP receptor.

PMID- 12519065
TI  - Synthesis and structure-affinity relationship investigations of 5-heteroaryl
      substituted analogues of the antipsychotic sertindole. A new class of highly
      selective alpha(1) adrenoceptor antagonists.
AB  - A new class of 5-heteroaryl-substituted 1-(4-fluorophenyl)-3-(4-piperidinyl)-1H
      indoles as highly selective and potentially CNS-active alpha 1-adrenoceptor
      antagonists is described. The compounds are derived from the antipsychotic
      sertindole. The structure-affinity relationships of the 5-heteroaryl
      substituents, and the substituents on the piperidine nitrogen atom were optimized
      with respect to affinity for alpha 1 adrenoceptors and selectivity in respect to
      dopamine (D(1-4)) and serotonin (5-HT(1A-1B) and 5-HT(2A,2C)) receptors. The most
      selective compound obtained, 3-[4-[1-(4-fluorophenyl)-5-(1-methyl-1,2,4-triazol-3
      yl)-1H-indol-3-yl]-1-piperidinyl]propionitrile (15c), has affinities of 0.99,
      3.2, and 9.0 nM for the alpha(1a), alpha(1b), and alpha(1d) adrenoceptor
      subtypes, respectively, and a selectivity for adrenergic alpha(1a) receptors in
      respect to dopamine D2, D3, and D4 and serotonin 5-HT(2A) and 5-HT(2C) higher
      than 900, comparable to the selectivity of prazosin. In addition, the compound is
      more than 150-fold selective in respect to serotonin 5-HT(1A) and 5-HT(1B)
      receptors. A new basic pharmacophore for alpha 1-adrenoceptor antagonists based
      on a previously reported pharmacophore model for dopamine D2 antagonist is
      suggested.

PMID- 12519066
TI  - Identification of phenylisoxazolines as novel and viable antibacterial agents
      active against Gram-positive pathogens.
AB  - A new and promising group of antibacterial agents, collectively known as the
      oxazolidinones and exemplified by linezolid (PNU-100766, marketed as Zyvox), have
      recently emerged as important new therapeutic agents for the treatment of
      infections caused by Gram-positive bacteria. Because of their significance,
      extensive synthetic investigations into the structure-activity relationships of
      the oxazolidinones have been conducted at Pharmacia. One facet of this research
      effort has focused on the identification of bioisosteric replacements for the
      usual oxazolidinone A-ring. In this paper we describe studies leading to the
      identification of antibacterial agents incorporating a novel isoxazoline A-ring
      surrogate. In a gratifying result, the initial isoxazoline analogue prepared was
      found to exhibit in vitro antibacterial activity approaching that of the
      corresponding oxazolidinone progenitor. The synthesis and antibacterial activity
      profile of a preliminary series of isoxazoline analogues incorporating either a C
      C or N-C linkage between their B- and C-rings will be presented. Many of the
      analogues exhibited interesting levels of antibacterial activity. The piperazine
      derivative 54 displayed especially promising in vitro activity and in vivo
      efficacy comparable to the activity and efficacy of linezolid.

PMID- 12519067
TI  - Discovery of a long-chain carbamoyl aminocarnitine derivative, a reversible
      carnitine palmitoyltransferase inhibitor with antiketotic and antidiabetic
      activity.
AB  - The synthesis and pharmacological activity of reversible CPT I inhibitors as
      potential antiketotic and antidiabetic drugs are reported. Such inhibitors
      constitute a series of enantiomerically pure aminocarnitine derivatives having
      the general formula (CH3)3N+CH2CH(ZR)CH2COO- (with Z = ureido, carbamate,
      sulfonamide, and sulfamide moieties; R = C7-C14 linear alkyl chains). A primary
      pharmacological screening based on the evaluation of CPT I activity in intact rat
      liver (L-CPT I) mitochondria revealed the best activity for the (R) forms of
      ureidic derivative 17 (ZR = NHCONHR, R = C14), sulfonamidic derivative 7 (ZR =
      NHSO2R, R = C12), and sulfamidic derivative 9 (ZR = NHSO2NHR, R = C11). The IC50
      values are 1.1, 0.7, and 0.8 microM, respectively. For the carbamic derivative 11
      (ZR = NHCOOR, R = C8), an IC50 of 9.5 microM was observed. In addition, an
      extraordinarily high selectivity toward the liver isoform with respect to the
      heart isoform (muscle-CPT I identical with M-CPT I) was found for the ureidic
      compound 17 (IC50(M-CPT I) vs IC50(L-CPTI) = 39.4), as well as for other ureidic
      or carbamic compounds. Diabetic db/db mice treated orally with 17 and 7 for 45
      days at a dose of 50 mg/kg twice a day showed a good reduction of serum glucose
      levels with respect to the untreated db/db mice (p < 0.01). In addition, 17
      showed antiketotic activity in normal fasted rats. 17 has been selected for
      development as a potential antiketotic and antidiabetic drug.

PMID- 12519068
TI  - Synthesis and benzodiazepine receptor affinity of pyrazolo[1,5-a]pyrimidine
      derivatives. 3. New 6-(3-thienyl) series as alpha 1 selective ligands.
AB  - New 3-aryl-6-(3-thienyl)pyrazolo[1,5-a]pyrimidin-7-ones (2a-j) are synthesized
      and evaluated in vitro on Bz/GABA(A) receptors and on recombinant benzodiazepine
      receptors (alpha x beta 2/3 gamma 2; x = 1-3, 5) expressed in HEK293 cells. SAR
      studies on the new compounds are conducted and molecular modeling is accomplished
      to better investigate requirements leading to subtype selectivity. Some of the
      synthesized compounds are tested in vivo to explore their pharmacological effect
      as a consequence of their high alpha 1 beta 2 gamma 2 subtype selectivity
      observed in vitro.

PMID- 12519069
TI  - The role of the side chain in determining relative delta- and kappa-affinity in
      C5'-substituted analogues of naltrindole.
AB  - The role of the side chain in 5'-substituted analogues of naltrindole has been
      further explored with the synthesis of series of amides, amidines, and ureas.
      Amidines (8, 13) had greatest selectivity for the kappa receptor, as predicted
      from consideration of the message-address concept. It was also found that an
      appropriately located carbonyl group, in ureas (10) and amides (7), led to
      retention of affinity and antagonist potency at the delta receptor.

PMID- 12519070
TI  - Treponema denticola cystalysin exhibits significant alanine racemase activity
      accompanied by transamination: mechanistic implications.
AB  - To obtain information on the reaction specificity of cystalysin from the
      spirochaete bacterium Treponema denticola, the interaction with L- and D-alanine
      has been investigated. Binding of both alanine enantiomers leads to the
      appearance of an external aldimine absorbing at 429 nm and of a band absorbing at
      498 nm, indicative of a quinonoid species. Racemization and transamination
      reactions were observed to occur with both alanine isomers as substrates. The
      steady-state kinetic parameters for racemization, k (cat) and K (m), for L
      alanine are 1.05+/-0.03 s(-1) and 10+/-1 mM respectively, whereas those for D
      alanine are 1.4+/-0.1 s(-1) and 10+/-1 mM. During the reaction of cystalysin with
      L- or D-alanine, a time-dependent loss of beta-elimination activity occurs
      concomitantly with the conversion of the pyridoxal 5'-phosphate (PLP) coenzyme
      into pyridoxamine 5'-phosphate (PMP). The catalytic efficiency of the half
      transamination of L-alanine is found to be 5.3x10(-5) mM(-1) x s(-1), 5-fold
      higher when compared with that of D-alanine. The partition ratio between
      racemization and half-transamination reactions is 2.3x10(3) for L-alanine and
      1.4x10(4) for D-alanine. The pH dependence of the kinetic parameters for both the
      reactions shows that the enzyme possesses a single ionizing residue with p K
      values of 6.5-6.6, which must be unprotonated for catalysis. Addition of pyruvate
      converts the PMP form of the enzyme back into the PLP form and causes the
      concomitant recovery of beta-elimination activity. In contrast with other PLP
      enzymes studied so far, but similar to alanine racemases, the apoform of the
      enzyme abstracted tritium from C4' of both (4' S)- and (4' R)-[4'-(3)H]PMP in the
      presence of pyruvate. Together with molecular modelling of the putative binding
      sites of L- and D-alanine at the active site of the enzyme, the implications of
      these studies for the mechanisms of the side reactions catalysed by cystalysin
      are discussed.

PMID- 12519071
TI  - Mastoparan binds to glycogen phosphorylase to regulate sarcoplasmic reticular
      Ca2+ release in skeletal muscle.
AB  - The ryanodine receptor, a Ca(2+)-releasing channel in sarcoplasmic reticulum
      (SR), plays an important role in the excitation-contraction coupling of skeletal
      muscle. In a previous study [Hirata, Nakahata and Ohizumi (2000) Mol. Pharmacol.
      57, 1235-1242], we reported that mastoparan caused Ca(2+) release through
      ryanodine receptor from the heavy fraction of SR (HSR) isolated from rabbit
      skeletal muscle, and that it specifically bound to a 97 kDa protein which was
      distinct from Ca(2+)-pump or triadin. The present study was undertaken to
      identify and characterize the 97 kDa mastoparan-binding protein. The 97 kDa
      protein was purified from solubilized HSR by DEAE-Sepharose column chromatography
      and preparative SDS/PAGE. The partial amino acid sequence of the purified 97 kDa
      protein was matched with that of glycogen phosphorylase (GP). The proteolytic
      cleavage pattern of the 97 kDa protein was identical with that of GP.
      Furthermore, [(125)I-Tyr(3)]mastoparan specifically bound to GP. Interestingly,
      mastoparan-induced Ca(2+) release was inhibited by exogenous addition of GP-a,
      and mastoparan dissociated GP from HSR. These results indicate that the 97 kDa
      mastoparan-binding protein is GP, which negatively regulates Ca(2+) release from
      HSR. There may be a functional cross-talk between Ca(2+) release from HSR and
      glycogenolysis for energy supply mediated through GP in skeletal muscles.

PMID- 12519072
TI  - Effects of prenatal glucocorticoid exposure on cardiac calreticulin and
      calsequestrin protein expression during early development and in adulthood.
AB  - Overexpression of the conserved Ca(2+)-binding proteins calreticulin and
      calsequestrin impairs cardiac function, leading to premature death. Calreticulin
      is vital for embryonic development, but also impairs glucocorticoid action.
      Glucocorticoid overexposure during late fetal life causes intra-uterine growth
      retardation and programmed hypertension in adulthood. To determine whether intra
      uterine growth retardation or programmed hypertension was associated with altered
      calreticulin or calsequestrin expression, effects of prenatal glucocorticoid
      overexposure (maternal dexamethasone treatment on days 15-21 of pregnancy) were
      examined during fetal life and postnatal development until adulthood (24 weeks).
      Dexamethasone (100 or 200 microg/kg of maternal body weight) was administered via
      osmotic pump. Calreticulin was detected as a 55 kDa band and calsequestrin as 55
      and 63 kDa bands in 21 day fetal hearts. Only the 55 kDa calsequestrin band was
      detected postnatally. Prenatal glucocorticoid overexposure at the higher dose
      decreased calreticulin protein expression (26%; P <0.05) but increased
      calsequestrin protein expression, both 55 and 63 kDa bands, by 87% ( P <0.01) and
      78% ( P <0.01); only the 55 kDa calsequestrin band was increased at the lower
      dose (66%; P <0.05). Offspring of dams treated at the lower dexamethasone dose
      were studied further. In control offspring, cardiac calreticulin protein
      expression declined between 2 and 3 weeks of age, and remained suppressed until
      adulthood. Cardiac calsequestrin protein expression increased 2-fold between
      fetal day 21 and postnatal day 1 and continued to increase until adulthood, at
      which time it was 3.4-fold higher ( P <0.001). Prenatal dexamethasone exposure
      minimally affected postnatal calsequestrin protein expression, but the postnatal
      decline in calreticulin protein expression was abrogated and calreticulin protein
      expression in adulthood was 2.2-fold increased ( P <0.001) compared with adult
      controls. In view of the known associations between cardiac calreticulin
      overexpression and impaired cardiac function, targeted up-regulation of
      calreticulin may contribute to the increased risk of adult heart disease
      introduced as a result of prenatal overexposure to glucocorticoids.

PMID- 12519073
TI  - Aorsin, a novel serine proteinase with trypsin-like specificity at acidic pH.
AB  - A proteinase that hydrolyses clupeine and salmine at acidic pH, called aorsin,
      was found in the fungus Aspergillus oryzae. Purified aorsin also hydrolysed
      benzyloxycarbonyl-Arg-Arg-4-methylcoumaryl-7-amide optimally at pH 4.0. The
      specificity of aorsin appeared to require a basic residue at the P(1) position
      and to prefer paired basic residues. Aorsin activated plasminogen and converted
      trypsinogen to trypsin. The trypsin-like activity was inhibited strongly by
      antipain or leupeptin, but was not inhibited by any other standard inhibitors of
      peptidases. To identify the catalytic residues of aorsin, a gene was cloned and
      an expression system was established. The predicted mature protein of aorsin was
      35% identical with the classical late-infantile neuronal ceroid lipofuscinosis
      protein CLN2p and was 24% identical with Pseudomonas serine-carboxyl proteinase,
      both of which are pepstatin-insensitive carboxyl proteinases. Several putative
      catalytic residues were mutated. The k (cat)/ K(m) values of the mutant enzymes
      Glu(86)-->Gln, Asp(211)-->Asn and Ser(354)-->Thr were 3-4 orders of magnitude
      lower and Asp(90)-->Asn was 21-fold lower than that of wild-type aorsin,
      indicating that the positions are important for catalysis. Aorsin is another of
      the S53 family serine-carboxyl proteinases that are not inhibited by pepstatin.

PMID- 12519074
TI  - Intersubunit interaction and catalytic activity of catechol 2,3-dioxygenases.
AB  - Catechol 2,3-dioxygenases (C23Os; EC 1.3.11.2) form a large protein family that
      is divided into several subgroups. Amino acid sequences of C23Os belonging to
      subgroup I.2.A and those belonging to I.2.B are found to be approx. 50%
      identical. When the central parts of the C23O sequences belonging to I.2.B were
      fused with the N-terminal and C-terminal sequences of I.2.A C23O, the hybrid
      enzymes were not active. To understand why these hybrid C23Os were inactive,
      hybrids between XylE(P) (C23O found in a Pseudomonas strain; subgroup I.2.A) and
      XylE(S) (C23O found in a Sphingomonas strain; subgroup I.2.B) were constructed.
      HB3-C23O consisted mostly of the XylE(S) sequence, except that its C-terminal end
      was derived from XylE(P). While HB3-C23O was not active, HB4-C23O, carrying
      shorter C-terminal XylE(P) sequences than HB3-C23O, was active. This observation
      indicated that certain amino acid residues at the C-terminus were crucial for
      C23O activity in the hybrid forms of enzymes between XylE(P) and XylE(S).
      According to the crystal structure of XylE(P), the C-terminal region is involved
      in the formation of a quaternary structure. Amino acid differences between HB3
      C23O and HB4-C23O included the specific beta-strand for oligomerization. Thus the
      quaternary structures of active C23Os, XylE(S), XylE(P) and HB4-C23O, as well as
      that of inactive HB3-C23O, were examined. Active enzymes XylE(S), XylE(P) and HB4
      C23O were homotetrameric, while HB3-C23O existed only as a monomer. We concluded
      that hybrids of subgroups I.2.A and I.2.B were often inactive because of a defect
      in their oligomerization.

PMID- 12519075
TI  - Beta1 integrin and alpha-dystroglycan binding sites are localized to different
      laminin-G-domain-like (LG) modules within the laminin alpha5 chain G domain.
AB  - Laminins are a group of extracellular-matrix proteins important in development
      and disease. They are heterotrimers, and specific domains in the different chains
      have specialized functions. The G domain of the alpha5 chain has now been
      produced in transfected mammalian cells as single modules and two tandem arrays,
      alpha5LG1-3 and alpha5LG4-5 (LG is laminin G domain-like). Using these fragments
      we produced specific polyclonal antibodies functional in immunoblotting and
      immunofluorescence studies and in solid-phase assays. Both alpha5LG tandem arrays
      had physiologically relevant affinities for sulphated ligands such as heparin and
      sulphatides. Cells adhered to these fragments and acquired a spread morphology
      when plated on alpha5LG1-3. Binding of integrins alpha3beta1 and alpha6beta1 was
      localized to the alpha5LG1-3 modules, and alpha-dystroglycan binding was
      localized to the alpha5LG4-5 modules, thus locating these activities to different
      LG modules within the laminin alpha5 G domain. However, both these activities
      were of relatively low affinity, indicating that integrin-mediated cell adhesion
      to the laminin 10/11 alpha5G domain depends on contributions from the other
      chains of the heterotrimer and that high-affinity alpha-dystroglycan binding
      could be dependent on specific Ca(2+)-ion-co-ordinating amino acids absent from
      alpha5LG4-5.

PMID- 12519076
TI  - Converging signals synergistically activate the LAMC2 promoter and lead to
      accumulation of the laminin gamma 2 chain in human colon carcinoma cells.
AB  - The trimeric extracellular matrix molecule laminin-5 and its constituent chains
      (alpha 3, beta 3, gamma 2) are normally not detectable intracellularly in
      intestinal epithelial cells but the laminin gamma 2 chain can be detected in
      cancer cells at the invasive front of a subset of colon carcinomas. These cells
      are subjected to cytokines such as transforming growth factor beta 1 (TGF-beta 1)
      and hepatocyte growth factor (HGF), produced by the tumour cells or by the
      surrounding stromal cells. The purpose of the present work was to investigate
      whether TGF-beta 1 and HGF, known to stimulate the LAMC2 gene encoding the
      laminin gamma 2 chain, might synergize to activate the LAMC2 promoter, and to
      identify the promoter elements involved. We find evidence for synergy between TGF
      beta and HGF with respect to laminin gamma 2 chain expression and promoter
      activation and demonstrate that this requires the 5' activator protein-1 (AP-1)
      element of the promoter and an additional upstream element which is also
      responsive to co-expression of the Smad3 protein from the TGF-beta signalling
      pathway. The transcripts encoding the other laminin-5 chains are not
      synergistically activated by HGF and TGF-beta. Thus the synergistic activation of
      the LAMC2 gene is mediated via different cis-elements and results in an
      overproduction of the laminin gamma 2 chain relative to the other laminin-5
      constituent chains. This difference may explain why laminin gamma 2 chains
      accumulate in the cells at the invasive front of colon carcinomas.

PMID- 12519077
TI  - Identification by site-directed mutagenesis of amino acids contributing to ligand
      binding specificity or signal transduction properties of the human FP prostanoid
      receptor.
AB  - Prostanoid receptors belong to the class of heptahelical plasma membrane
      receptors. For the five prostanoids, eight receptor subtypes have been
      identified. They display an overall sequence similarity of roughly 30%. Based on
      sequence comparison, single amino acids in different subtypes of different
      species have previously been identified by site-directed mutagenesis or in hybrid
      receptors that appear to be essential for ligand binding or G-protein coupling.
      Based on this information, a series of mutants of the human FP receptor was
      generated and characterized in ligand-binding and second-messenger-formation
      studies. It was found that mutation of His-81 to Ala in transmembrane domain 2
      and of Arg-291 to Leu in transmembrane domain 7, which are putative interaction
      partners for the prostanoid's carboxyl group, abolished ligand binding. Mutants
      in which Ser-263 in transmembrane domain 6 or Asp-300 in transmembrane domain 7
      had been replaced by Ala or Gln, respectively, no longer discriminated between
      prostaglandins PGF(2alpha) and PGD(2). Thus distortion of the topology of
      transmembrane domains 6 and 7 appears to interfere with the cyclopentane ring
      selectivity of the receptor. PGF(2alpha)-induced inositol formation was strongly
      reduced in the mutant Asp-300Gln, inferring a role for this residue in agonist
      induced G-protein activation.

PMID- 12519078
TI  - Biochemical filtering of a protein-protein docking simulation identifies the
      structure of a complex between a recombinant antibody fragment and alpha
      bungarotoxin.
AB  - The structural characterization of a complex of alpha-bungarotoxin with a
      recombinant antibody fragment that mimics the acetylcholine receptor was achieved
      using docking simulation procedures. To drive the computer simulation towards a
      limited set of solutions with biological significance, a filter, incorporating
      general considerations of antigen-antibody interactions, specificity of the
      selected antibody fragment and results from alpha-bungarotoxin epitope mapping,
      was adopted. Two similar structures were obtained for the complex, both of them
      stabilized by cation-pi and hydrophobic interactions due to tyrosilyl residues of
      the antibody fragment. Site-directed mutagenesis studies, removing each of the
      latter aromatic residues and causing full inactivation of the interaction process
      between the antibody fragment and the neurotoxin, support the validity of the
      calculated structure of the complex.

PMID- 12519079
TI  - Identification of galectin I and thioredoxin peroxidase II as two arsenic-binding
      proteins in Chinese hamster ovary cells.
AB  - In this study, we report the identification of two arsenic-binding proteins from
      Chinese hamster ovary (CHO) cells. The crude extract derived from CHO and SA7
      (arsenic-resistant CHO cells) was applied to a phenylarsine oxide-agarose
      affinity column, and after extensive washing, the absorbed proteins were eluted
      with buffers containing 20 mM 2-mercaptoethanol (2-ME) or dithiothreitol (DTT).
      Three differentially expressed proteins, galectin 1 (Gal-1; in the 2-ME-eluted
      fraction from CHO cells), glutathione S-transferase P-form (GST-P) and
      thioredoxin peroxidase II (TPX-II), respectively in the 2-ME- and DTT-eluted
      fractions from SA7 cells, were identified by partial amino acid sequence analysis
      after separation by SDS/PAGE. The GST-P protein has been previously shown to
      facilitate the excretion of sodium arsenite [As(III)] from SA7 cells. TPX II was
      detected predominately in SA7 cells [routinely cultured in As(III)-containing
      medium], but not in CHO or SA7N (a revertant of SA7 cells cultured in regular
      medium) cells. In contrast, Gal-1 was specifically identified in CHO and SA7N
      cells, but not in SA7 cells. The preferential expression of Gal-1 in CHO cells
      and TPX-II in SA7 cells was further illustrated by quantitative PCR analysis. The
      binding of Gal-1 and TPX-II with As(III) was further verified by both co
      immunoprecipitation and co-elution of Gal-1 and TPX-II with As(III). It is
      suggested that Gal-1 and TPX-II are two proteins that serve as high-affinity
      binding sites for As(III) and thus both may be involved in the biological action
      of As(III).

PMID- 12519080
TI  - A synthetic peptide from the heparin-binding domain III (repeats III4-5) of
      fibronectin promotes stress-fibre and focal-adhesion formation in melanoma cells.
AB  - Cell adhesion to fibronectin results in formation of actin stress fibres and
      focal adhesions. In fibroblasts, this response requires two co-operative signals
      provided by interactions of the RGD sequence with alpha5beta1 integrin and the
      heparin-binding domain II (Hep II) domain with syndecan-4. Within Hep II, this
      activity was mapped to repeat III13 and to the peptide FN-C/H-V(WQPPRARITGY,
      repeat III14). We previously described that the synthetic heparin-binding
      peptide/III5 (HBP/III5) (WTPPRAQITGYRLTVGLTRR, repeat III5) binds heparin and
      mediates cell adhesion via chondroitin sulphate proteoglycans. We have now
      studied whether HBP/III5 co-operates with alpha5beta1 and drives a full
      cytoskeletal response in melanoma cells. SKMEL-178 cells attached and spread on
      the RGD-containing FNIII7-FNIII10 (FNIII7-10) fragment, but did not form stress
      fibres or focal adhesions. Co-immobilization of HBP/III5 with FNIII7-10 or adding
      soluble HBP/III5 to cells prespread on FNIII7-10, effectively induced these
      structures. Cell transfection with dominant-negative N19RhoA, a member of the
      small GTPase family, abolished the HBP/III5 effect. Both chondroitinase and
      heparitinase diminished focal adhesions, indicating that both types of
      proteoglycans bound HBP/III5 in melanoma cells. We have mapped the active
      sequence of HBP/III5 to YRLTVGLTRR, which is a novel sequence in fibronectin with
      focal-adhesion-promoting activity. The last two arginine (R) residues of this
      sequence are required for activity, since their replacement by alanine completely
      abrogated the HBP/III5 cytoskeletal effect. Moreover, this sequence is also
      active in the context of large fibronectin fragments. Our results establish that
      the Hep III region provides co-operative signals to alpha5beta1 for the
      progression of the cytoskeletal response and that these include activation of
      RhoA.

PMID- 12519081
TI  - Increased plasma urotensin II levels in patients with diabetes mellitus.
AB  - Urotensin II (UII) is the most potent vasoconstrictor peptide, whereas it acts as
      a vasodilator on some arteries. We studied plasma levels of UII in diabetic
      patients with normal serum creatinine levels (<90 micromol/l) and the expression
      of UII and its receptor in cultured human vascular endothelial cells. Plasma UII
      levels were significantly elevated by 1.8-fold in diabetic patients without
      proteinuria (7.8+/-0.6 fmol/ml; P <0.0001) and 1.7-fold in those with overt
      proteinuria (7.3+/-0.9 fmol/ml; P =0.0018) when compared with healthy subjects
      (4.4+/-0.2 fmol/ml). No significant correlation was obtained between plasma UII
      levels and fasting blood sugar (P =0.631 and P =0.853 in non-proteinuric and
      proteinuric diabetic patients respectively), glycated haemoglobin levels (P
      =0.376 and P =0.888 respectively) or serum creatinine levels (P =0.301 and P
      =0.568 respectively). Reverse transcriptase-PCR analysis showed the expression of
      mRNAs encoding UII precursor and UII-receptor precursors in cultured human
      coronary artery endothelial cells and umbilical vein endothelial cells,
      suggesting that vascular endothelial cells are one of the sources of UII in
      blood. These findings suggest that elevation of plasma UII levels may be an
      important background factor in diabetic cardiovascular and organ complications in
      diabetic subjects without renal failure.

PMID- 12519082
TI  - Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and
      hyperthyroidism.
AB  - We have examined insulin action on glucose metabolism in six hypothyroid patients
      before and after regular thyroid hormone treatment, and in six healthy volunteers
      before and after transient induction of moderate hyperthyroidism. Insulin was
      infused under euglycaemic and eukalaemic clamps. An appropriate amino acid
      infusion was used to blunt insulin-induced decreases in amino acid levels.
      Glucose kinetics were assessed using a primed continuous infusion of [6,6
      (2)H(2)]glucose. The results showed that basal plasma insulin and glucose levels
      (i.e. before infusion) were similar in each case. Despite similar insulin
      infusion rates, the plateau value of insulin was lower after thyroid treatment in
      both hypothyroid patients and healthy volunteers. The rate of exogenous glucose
      needed to maintain plasma glucose at a steady-state level was increased by
      thyroid hormone in hypothyroid patients (P <0.05), but not in healthy volunteers.
      Thyroid treatment resulted in a significant increase in basal glucose disposal in
      both groups (P <0.05). Insulin, in conjunction with glucose and amino acids,
      significantly stimulated glucose disposal (P <0.05) under all conditions. The
      incremental increase in glucose disposal after infusion tended to be higher
      following thyroid hormone treatment, but this was not statistically significant.
      However, the ratio of the incremental increase in glucose disposal to the
      increase in plasma insulin was significantly improved after thyroid hormone
      treatment in hypothyroid patients (P <0.05). It was also increased in healthy
      volunteers, but not significantly. We conclude that thyroid hormones improve the
      ability of insulin to stimulate glucose disposal related to insulinaemia. This
      phenomenon may be highly sensitive, because it was only apparent at low thyroid
      hormone levels.

PMID- 12519084
TI  - Hartmann's solution and Ringer's lactate: targeting the fourth space.

PMID- 12519083
TI  - (Ab)normal saline and physiological Hartmann's solution: a randomized double
      blind crossover study.
AB  - In this double-blind crossover study, the effects of bolus infusions of 0.9%
      saline (NaCl) and Hartmann's solution on serum albumin, haematocrit and serum and
      urinary biochemistry were compared in healthy subjects. Nine young adult male
      volunteers received 2-litre intravenous infusions of 0.9% saline and Hartmann's
      solution on separate occasions, in random order, each over 1 h. Body weight,
      haematocrit and serum biochemistry were measured pre-infusion and at 1 h
      intervals for 6 h. Biochemical analysis was performed on pooled post-infusion
      urine. Blood and plasma volume expansion, estimated by dilutional effects on
      haematocrit and serum albumin, were greater and more sustained after saline than
      after Hartmann's solution (P <0.01). At 6 h, body weight measurements suggested
      that 56% of the infused saline was retained, in contrast with only 30% of the
      Hartmann's solution. Subjects voided more urine (median: 1,000 compared with 450
      ml) of higher sodium content (median: 122 compared with 73 mmol) after Hartmann's
      than after saline (both P =0.049), despite the greater sodium content of the
      latter. The time to first micturition was less after Hartmann's than after saline
      (median: 70 compared with 185 min; P =0.008). There were no significant
      differences between the effects of the two solutions on serum sodium, potassium,
      urea or osmolality. After saline, all subjects developed hyperchloraemia (>105
      mmol/l), which was sustained for >6 h, while serum chloride concentrations
      remained normal after Hartmann's (P <0.001 for difference between infusions).
      Serum bicarbonate concentration was significantly lower after saline than after
      Hartmann's (P =0.008). Thus excretion of both water and sodium is slower after a
      2-litre intravenous bolus of 0.9% saline than after Hartmann's solution, due
      possibly to the more physiological [Na(+)]/[Cl(-)] ratio in Hartmann's solution
      (1.18:1) than in saline (1:1) and to the hyperchloraemia caused by saline.

PMID- 12519085
TI  - The inflammatory macrophage: a story of Jekyll and Hyde.
AB  - Recent investigations have highlighted new roles for the macrophage (Mphi) in the
      biology of inflammation. Selective depletion of Mphis from inflamed sites has
      confirmed their predominant role in immune-mediated damage. The components of
      this injury have been dissected. Mphis mediate death of stromal, parenchymal and
      other immune cells by engaging the death programme, resulting in apoptosis. In
      addition, Mphis induce destruction of matrix and extracellular structures both
      directly and indirectly by inducing stromal cells to release matrix
      metalloproteinases. However, there is another side to the inflammatory Mphi.
      Evidence is provided that Mphis at the same sites possess the ability to aid cell
      proliferation, secrete and stabilize new matrix components and induce resident
      cells to secrete matrix components themselves. Mphi phagocytosis of apoptotic
      cells brings about a change from the cell-killing matrix-degrading cell to the
      matrix-generating cell-proliferating tissue-healing cell. Just as both Mphi types
      are necessary at the inflamed site, the right balance of these two populations is
      required for healing and resolution. Evidence of excessive inflammation as a
      manifestation of impaired phagocytosis of apoptotic cells emphasizes that defects
      in the transition from one Mphi type to another may account for the uncontrolled
      excessive inflammation seen in disease. Recent insights into the mechanisms by
      which apoptotic cells signal the change of function to the Mphi offer the
      prospect of novel targets for manipulation of Mphis in the inflamed tissue.

PMID- 12519086
TI  - Effects of inhibition of ATP-sensitive potassium channels on metabolic
      vasodilation in the human forearm.
AB  - Experimental data suggest that vascular ATP-sensitive potassium (K(ATP)) channels
      may be an important determinant of functional hyperaemia, but the contribution of
      K(ATP) channels to exercise-induced hyperaemia in humans is unknown. Forearm
      blood flow was assessed in 39 healthy subjects (23 males/16 females; age 22+/-4
      years) using the technique of venous occlusion plethysmography. Resting forearm
      blood flow and functional hyperaemic blood flow (FHBF) were measured before and
      after brachial artery infusion of the K(ATP) channel inhibitors glibenclamide (at
      two different doses: 15 and 100 microg/min) and gliclazide (at 300 microg/min).
      FHBF was induced by 2 min of non-ischaemic wrist flexion-extension exercise at 45
      cycles/min. Compared with vehicle (isotonic saline), glibenclamide at either 15
      microg/min or 100 microg/min did not significantly alter resting forearm blood
      flow or peak FHBF. The blood volume repaid at 1 and 5 min after exercise was not
      diminished by glibenclamide. Serum glucose was unchanged after glibenclamide, but
      plasma insulin rose by 36% (from 7.2+/-0.8 to 9.8+/-1.3 m-units/l; P =0.02) and
      150% (from 9.1+/-1.3 to 22.9+/-3.5 m-units/l; P =0.002) after the 15 and 100
      microg/min infusions respectively. Gliclazide also did not affect resting forearm
      blood flow, peak FHBF, or the blood volume repaid at 1 and 5 min after exercise,
      compared with vehicle (isotonic glucose). Gliclazide induced a 12% fall in serum
      glucose (P =0.009) and a 38% increase in plasma insulin (P =0.001). Thus
      inhibition of vascular K(ATP) channels with glibenclamide or gliclazide does not
      appear to affect resting forearm blood flow or FHBF in healthy humans. These
      findings suggest that vascular K(ATP) channels may not play an important role in
      regulating basal vascular tone or skeletal muscle metabolic vasodilation in the
      forearm of healthy human subjects.

PMID- 12519087
TI  - Chemokines in the pathogenesis of liver disease: so many players with poorly
      defined roles.
AB  - Many new chemokines have been described in recent years, resulting in a new
      classification of these chemoattractant proteins. The characterization of the
      biological functions of most chemokines relates to their ability to induce
      chemotaxis in circulating inflammatory cells. However, it is now clear that
      chemokines have a much wider biological role, including angiogenesis,
      carcinogenesis and involvement in the pathogenesis of HIV infection. Our
      understanding of the role of chemokines in the pathogenesis of disorders of the
      lungs and brain outstrips that with regard to disorders of the liver. An
      increased understanding of the role of chemokines in the pathogenesis of liver
      disease may lead to the development of novel therapies for hepatic disease.

PMID- 12519088
TI  - Urotensin II: a new player in vascular and myocardial disease?

PMID- 12519089
TI  - Peripheral blood leucocyte functional responses to acute eccentric exercise in
      humans are influenced by systemic stress, but not by exercise-induced muscle
      damage.
AB  - The effects of comparable lower-limb eccentric exercise that induces high (bench
      stepping; STEP) and low (repeated eccentric muscle action; ECC) systemic stress
      on neutrophil and monocyte phagocytic and respiratory burst activity, and
      activation antigen (CD11b, CD66b, CD64) expression, were compared in
      recreationally active subjects (20-37 years old). Leucocyte responses were
      determined before and 4, 24, 48 and 72 h after exercise using whole-blood flow
      cytometry. Serum creatine kinase (CK) activity and perceived muscle soreness
      [delayed-onset muscle soreness (DOMS)] were assessed at the same time points up
      to 96 h; as a control, measurements were taken during 5 days of rest. DOMS in
      quadriceps and contralateral triceps surae peaked 24-72 h after STEP (P <0.05)
      and 48-72 h after ECC (P <0.05), whereas serum CK activity (mean+/-S.E.M.) was
      only higher than baseline after ECC (15,123+/-3,488 at 96 h compared with 115+/
      29 units x l(-1) pre-exercise; P <0.01). The total leucocyte count increased from
      (5.4+/-0.4) x 10(9) x l(-1) and (5.7+/-0.5) x 10(9) x l(-1) at baseline to (7.6+/
      0.5)x10(9) x l(-1) and (7.0+/-0.5) x 10(9) x l(-1) at 4 h after STEP and ECC
      respectively; this was largely attributable to changes in the neutrophil count (P
      <0.05). The proportion of neutrophils undergoing phagocytosis and respiratory
      burst was unchanged 4 h after ECC and STEP, which, given the increase in
      neutrophil count after exercise, would suggest an overall improvement in systemic
      neutrophil microbicidal potential. The intensity of neutrophil (P =0.01) and
      monocyte (P <0.05) phagocytosis and neutrophil respiratory burst responses (P
      <0.05) was only increased 24 h after STEP, whereas no changes in these measures
      were observed after ECC. Activation antigen expression was unchanged in all
      groups. These findings suggest that systemic stress evoked during an acute bout
      of eccentric exercise has a greater influence on subsequent leucocyte functional
      responses than the degree of muscle damage induced.

PMID- 12519090
TI  - Effects of angiotensin-converting enzyme inhibition and calcium channel blockade
      on cardiac apoptosis in rats with 2K1C (two-kidney/one-clip) renovascular
      hypertension.
AB  - Apoptosis plays a role in the regulation of heart mass and architecture, and
      might contribute to the cardiac remodelling seen in renovascular hypertension. It
      is not known whether the beneficial effects of angiotensin-converting enzyme
      (ACE) inhibition or calcium channel blockade on cardiac remodelling are linked to
      the modulation of apoptosis. To test this hypothesis, we established four groups
      of rats: (i) sham-operated controls, (ii) a group that underwent the two
      kidney/one-clip (2K1C) procedure, (iii) a group with 2K1C treated for 12 weeks
      with quinapril (6 mg x day(-1) x kg(-1)), and (iv) a group with 2K1C treated for
      12 weeks with diltiazem (24 mg x day(-1) x kg(-1)). Treatment started 2 weeks
      after clipping. Systolic blood pressure was reduced to a similar extent by
      quinapril and diltiazem (2K1C, 223+/-19 mmHg; 2K1C+quinapril, 149+/-15 mmHg;
      2K1C+diltiazem, 160+/-40 mmHg; both P <0.01 compared with 2K1C alone). Left
      ventricular weight, interstitial fibrosis and perivascular fibrosis were reduced
      significantly by both drugs. The apoptotic index (apoptotic cells/total cell
      number) was increased 21.6-fold (P <0.01) after quinapril treatment as compared
      with the 2K1C group, but was not affected by calcium channel blockade. In
      conclusion, our study demonstrates that ACE inhibition, in contrast with calcium
      channel blockade, may cause regression of cardiac hypertrophy/remodelling in 2K1C
      renovascular hypertensive rats through enhanced apoptosis.

PMID- 12519091
TI  - Vasoactive properties of lignocaine administered by iontophoresis in human skin.
AB  - The vasoactivity of lignocaine has an important influence on its clinical
      efficacy and systemic vascular absorption. The aim of this study was to evaluate
      its vasoactive properties when administered by the non-invasive technique of
      iontophoresis. We used laser Doppler imaging to measure the forearm skin blood
      flow responses of seven healthy young males to iontophoretic delivery of two
      preparations of 20 g/l of lignocaine hydrochloride, one containing the
      preservatives methylparaben and propylparaben and one without. The subjects were
      blind to the order of drug administration, and we assessed analgesia at the sites
      using a pinprick test. Delivery of both preparations of (positively charged)
      lignocaine under the anode caused demonstrable analgesia, but no change in skin
      blood flow. An increase in perfusion was measured, however, when the preservative
      containing preparation was administered under the cathode. There was little or no
      response to the solution without preservatives, although the difference in
      response between the two preparations was not statistically significant (P
      =0.063). Although there were no vasoactive effects of lignocaine at the
      relatively low dose used in the present study, our results suggest that the
      preservatives methylparaben and propylparaben are the most likely cause of the
      vasodilatation that we observed under the cathode, and may therefore have a
      significant influence on the vasoactivity of this preparation when administered
      by injection. Both are negatively charged in solution and have been reported to
      possess vasodilator properties. It might be worth considering the use of
      alternative, non-vasoactive preservatives in local anaesthetic preparations, or
      avoiding the use of additives altogether, when this is feasible.

PMID- 12519092
TI  - Renal function and angiotensin AT1 receptor expression in young rats following
      intrauterine exposure to a maternal low-protein diet.
AB  - Recent studies have proposed a link between impaired nephrogenesis, decreased
      activity of the renin-angiotensin system and the onset of hypertension in rats
      exposed in the uterus to a maternal low-protein diet. However, there is no
      detailed information about renal function in this model; hence the aim of the
      present study was to assess renal function in young (4-week-old) rats exposed in
      the uterus to a maternal low-protein diet. Pregnant Wistar rats were fed
      isocalorific diets containing either 18% (normal protein; offspring denoted NP
      rats) or 9% (low protein; offspring denoted LP rats) (w/w) protein from
      conception until birth. At 4 weeks of age, male offspring were anaesthetized and
      prepared for the study of renal function, during which animals received saline
      alone, a bolus of enalapril (5 mg.kg(-1)) or a bolus of enalapril followed by an
      infusion of angiotensin II (30 ng.min(-1).kg(-1)). Under control conditions,
      renal haemodynamic and tubular function did not differ. However, when challenged
      with angiotensin II, LP rats responded with a greater decrease in glomerular
      filtration rate than did NP rats [NP, 2.0+/-0.2 ml.min(-1).g(-1) kidney weight (
      n =9); LP, 1.0+/-0.2 ml.min(-1).g(-1) kidney weight ( n =5); P <0.05]. Renal
      electrolyte excretion did not differ. LP rats had significantly fewer glomeruli
      than NP rats ( P <0.01). Renal angiotensin II AT(1) receptor expression was
      increased ( P <0.01) by 24% in LP rats. It is concluded that blood pressure may
      be elevated in LP rats in order to maintain glomerular filtration rate against a
      background of fewer nephrons. Increased AT(1) receptor expression, which may
      arise as a result of the direct effect of protein restriction or in response to
      the reported decrease in renal tissue angiotensin II concentration, could also
      contribute to the elevated blood pressure of this model.

PMID- 12519093
TI  - Effects of common polymorphisms in the alpha1A-, alpha2B-, beta1- and beta2
      adrenoreceptors on haemodynamic responses to adrenaline.
AB  - Common naturally occurring polymorphisms have been identified in the coding
      regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR)
      genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR
      R389G, beta(2)-AR G16R and beta(2)-AR Q27E] and are associated with modified in
      vivo and in vitro functionality. We tested their possible effects on the
      haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160 ng/kg of
      body weight per min; 5 min for each infusion rate) before and after beta-blockade
      (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood
      pressure (BP), ECG, coronary flow velocity and plasma adrenaline and
      noradrenaline. The Cys/Cys (CC) genotype of the alpha(1A)-AR R492C polymorphism
      was associated with a longer ECG PR interval before and during the adrenaline
      infusions. The deletion/deletion (D/D) genotype of the alpha(2B)-AR I/D
      polymorphism was associated with blunted coronary blood flow increases during the
      adrenaline infusion before beta-blockade. The beta(1)-AR R389G polymorphism was
      not associated with modified responses to infused adrenaline. Subjects carrying
      the Gly/Gly (GG) genotype of the beta(2)-AR G16R polymorphism demonstrated
      increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was
      decreased in the other genotype groups. These results suggest that, upon acute
      adrenaline infusion, the alpha(2B)-AR D/D genotype confers increased
      vasoconstriction and that the beta(2)-AR GG genotype confers reduced
      vasodilatation.

PMID- 12519094
TI  - Serotonergic dysregulation in bipolar disorders: a literature review of
      serotonergic challenge studies.
AB  - OBJECTIVES: Serotonin (5-hydroxytryptamine; 5-HT) and endocrine abnormalities
      have been repeatedly reported in bipolar disorders (BD). Useful methods to
      investigate 5-HT responsivity, and the interaction with neuroendocrine
      functioning, are provided by acute 5-HT challenge and depletion paradigms. In
      this review 5-HT challenges are limited to paradigms that stimulate 5-HT activity
      in BD. METHODS: Literature was searched for in electronic libraries: MEDLINE and
      PSYCHLIT, period 1966-2001. Papers describing effects of an acute 5-HT challenge
      on neuroendocrine functioning in BD patients were selected. RESULTS: Review of
      the literature revealed 15 studies: five papers described the effects of 5-HT
      challenges in manic BD patients, four papers in euthymic BD and seven in
      depressed BD patients. The reviewed 5-HT challenge paradigms are acute
      administration of oral and intravenous (i.v.) dosage of d,l-fenfluramine,
      tryptophan, 5-hydroxytryptophan, ipsapirone and buspirone. There were no papers
      which investigated neuroendocrine effects of m-chlorophenylpiperazine,
      clomipramine and citalopram in BD patients and were therefore not reviewed.
      CONCLUSIONS: The literature on 5-HT challenge procedures in BD shows evidence for
      a blunted prolactin (PRL) in mania and depression as well as a blunted cortisol
      in euthymic BD patients. This suggests that in both mania and depression similar
      changes in the 5-HT system are involved. It is speculated that blunting of
      cortisol responses in euthymic BD patients may be a result of chronically altered
      5-HT functioning, whereas changes in PRL release following 5-HT challenges
      reflect more state-dependent changes in 5-HT activity. The 5-HT responsivity in
      BD patients has also been associated with pharmacological treatment, suicidal
      behaviour, weight loss and age. Recommendations for future research are given.

PMID- 12519095
TI  - Frontal lobe differences in bipolar disorder as determined by proton MR
      spectroscopy.
AB  - OBJECTIVES: Proton magnetic resonance spectroscopy (MRS) provides insight into
      neurochemical processes. Imaging and postmortem studies have implicated
      abnormalities of structure and function within the frontal lobe. Patients with
      bipolar disorder having a manic or mixed episode were hypothesized to demonstrate
      metabolic abnormalities within the frontal lobe. METHODS: Seventeen patients with
      bipolar disorder type I (ages 16-35 years, mean 22 +/- 7.3 years) hospitalized
      for a manic (n = 9) or mixed (n = 8) episode and 21 healthy subjects (ages 16-35
      years, mean 21.7 +/- 5.2 years) were evaluated with proton MRS. The gray matter
      medially and white matter laterally within the frontal lobe were sampled.
      Metabolite concentrations were calculated for each voxel, corrected for cerebral
      spinal fluid (CSF) contributions to the voxel, and compared between study
      populations. RESULTS: Patients demonstrated with multivariate analyses of
      variance (MANOVA) a significant overall difference in gray matter metabolite
      concentrations compared with healthy subjects. The largest effect sizes for group
      differences were found with reductions of N-acetyl aspartate (NAA) and Choline
      (Cho) concentrations (f = 0.41 and 0.37, respectively). A significant group
      difference with MANOVA in white matter metabolite concentrations was also
      observed with the largest effect size at f = 0.44 for elevation of the composite
      amino acid (AA) concentration. CONCLUSIONS: A reduction of NAA within the gray
      matter of patients suggests neuronal dysfunction. Altered phospholipid metabolism
      suggestive of a trend toward decreased volume is implicated with a reduction of
      Cho concentrations. Within white matter, composite concentrations of AAs were
      elevated in patients indicating altered neurotransmission.

PMID- 12519096
TI  - Pharmacotherapy patterns in the treatment of bipolar disorder.
AB  - OBJECTIVES: To assess medication use patterns of patients with bipolar disorder,
      and, through multivariate analysis, to elucidate the role of selected demographic
      and clinical factors on medication choice and use patterns. METHODS: Patients
      were privately insured individuals aged 18-64, continuously enrolled in a health
      plan for 15 months or longer during the years 1994-1998, and either diagnosed
      with bipolar disorder or prescribed lithium or valproate at least 90 days after
      the start of the study period. Medical and pharmacy claims data were used to
      analyze medication therapy over a 12-month period. RESULTS: First-generation
      antipsychotics were used by 16.4% of patients and second-generation agents by
      12.4%. Patients starting on antipsychotics tended to stay with them for 12 months
      or longer, while patients starting on anticonvulsants or antidepressants were
      more likely to stop therapy or to switch to another medication class. Patients
      treated with olanzapine appeared to have more psychiatric comorbidities and more
      psychiatric hospitalizations than users of first-generation agents. CONCLUSIONS:
      Although mood stabilizers and anticonvulsant agents are widely used to treat
      bipolar disorder, antipsychotic agents are also present in the treatment regimens
      of bipolar patients. Demographic and clinical factors were significant predictors
      of the choice of initial medication therapy and subsequent use patterns. In
      particular, patient gender and the number of psychiatric and physical
      comorbidities were significantly related to the course of medication therapy.

PMID- 12519097
TI  - The Maudsley bipolar disorder project. A survey of psychotropic prescribing
      patterns in bipolar I disorder.
AB  - OBJECTIVES: The outcome of Bipolar 1 Disorder (BD1) is greatly dependent on the
      adequacy and appropriateness of its treatment. As the treatment choices in BD1
      disorder are increasing the aim of this study was to examine the current use of
      the pharmacological agents in BD1 patients and its association with clinical
      characteristics. METHODS: Case note review of the pharmacotherapy of a sample of
      BD1 patients from a specified South London sector of a National Health Service
      Trust. RESULTS: Half of the patients were on mood-stabilizers (usually lithium)
      and their use was associated with female gender and multiple admissions.
      Antipsychotics were more commonly used in patients with psychotic features and
      multiple manic episodes. Antidepressants were rarely prescribed alone and were
      not associated with increased number of manic episodes. Combination treatments
      were mostly used in patients in acute episodes and with multiple
      hospitalizations. CONCLUSIONS: In ordinary care, the treatment of BD1 is often
      driven by symptoms and falls short of the existing practice guidelines.

PMID- 12519098
TI  - A pilot study of concordance therapy for individuals with bipolar disorders who
      are non-adherent with lithium prophylaxis.
AB  - OBJECTIVES: To assess the acceptability and feasibility of concordance therapy
      (CCT) in improving adherence with lithium prophylaxis in individuals with bipolar
      disorder. METHODS: Ten subjects with bipolar I disorder and self-reported
      problems with lithium adherence were recruited. Eight participated in a 6-month
      study of CCT delivered by an expert in cognitive therapy. Reliable and valid
      assessments of self-reported adherence with lithium, attitudes towards, and
      knowledge of lithium and serum plasma lithium levels were measured pre- and post
      intervention. Subjects' views of CCT were also recorded. RESULTS: Statistically
      significant improvements in attitudes towards lithium (mean score baseline = 6.8;
      follow up = 4.1; Effect size = 1.6) were associated with improvements in self
      reported adherence. Laboratory results demonstrated statistically significant
      increases in serum plasma lithium levels (mean increased from 0.41 to 0.6; effect
      size 1.7). Subjects viewed CCT as an acceptable intervention. However, only four
      of the 10 subjects completed all seven half-hour therapy sessions and homework
      tasks. CONCLUSIONS: This small open study suggests that CCT may represent a
      useful addition to the 'stepped care' package of treatment for individuals with
      bipolar disorders. Research is underway to assess its efficacy and to establish
      whether novice therapists can also apply the model effectively.

PMID- 12519099
TI  - Thyroid function in mixed and pure manic episodes.
AB  - OBJECTIVES: Associations of both overt thyroid disease as well as subclinical
      thyroid abnormalities with affective disorders have been well established.
      Similar associations have been reported with mixed mania and rapid cycling
      bipolar disorder. We tested for differences in overt and subclinical thyroid
      disease and subclinical differences in a large series of bipolar patients
      examined during mixed or pure manic episodes. METHODS: Rates of previously
      diagnosed thyroid disease were compared by sex, race and manic subtype (mixed
      versus pure) in 443 patients. Serum thyroid stimulating hormone (TSH) and free
      thyroxine (FT4) concentrations obtained from patients with no clinical thyroid
      disease collected during manic and mixed bipolar episodes were compared using
      ANOVA statistics. Race was also included in the model and age was covaried.
      RESULTS: Rates of thyroid disease, in particular hypothyroidism, were higher in
      females and white people, and increased with advancing age. No differences were
      noted between subjects sampled during mixed or pure manic episodes. In patients
      with no history of thyroid disease, serum TSH and FT4 concentrations did not
      differ between manic subtypes or between sexes. TSH levels however, were
      significantly lower in African Americans. CONCLUSIONS: We did not confirm past
      reports of associations of overt or subclinical thyroid disease with mixed manic
      episodes. African Americans had significantly lower serum TSH concentrations than
      white people, while FT4 levels did not differ.

PMID- 12519100
TI  - Health care utilization and costs among privately insured patients with bipolar I
      disorder.
AB  - OBJECTIVE: This study examined health care resource utilization and direct health
      care costs among patients diagnosed with bipolar I disorder in a privately
      insured population. METHODS: Health care claims data for 2883 patients with a
      primary diagnosis of bipolar disorder were compared over a 1-year period (1997)
      with claims data for 2883 randomly selected, age- and sex-matched, non-bipolar
      patients, all covered under the same large private insurer in USA. Resource use
      (i.e. original and refill pharmaceutical dispensing, medical and procedural
      services received, inpatient hospitalization, outpatient services, physician
      visits and emergency room treatment) and their costs are described overall, as
      well as by bipolar disorder diagnosis (based on ICD-9 codes) and type of care
      (i.e. mental health versus non-mental health). RESULTS: Bipolar patients utilized
      nearly three to four times the health care resources and incurred over four times
      greater costs per patient compared with the non-bipolar group during the 1-year
      period ($7663 versus $1962). Inpatient care (hospitalizations) accounted for the
      greatest disparity between groups, as it was the single-most costly resource in
      the bipolar group ($2779 versus $398). Patients with bipolar depression (among
      the single bipolar diagnostic categories of mixed, manic or depressed) incurred
      the highest health care costs. While mental health care cost was a significant
      component of total cost in the bipolar group, it accounted for only 22% of the
      total per-patient cost; in comparison, it accounted for only 6% of the total per
      patient cost in the non-bipolar group. CONCLUSION: Treatment of bipolar disorder,
      particularly inpatient care, is costly to patients and health insurers. Further
      study is needed to find ways to reduce the overall cost of managing these
      patients without jeopardizing patient care.

PMID- 12519101
TI  - Quetiapine in bipolar disorder and cocaine dependence.
AB  - OBJECTIVE: Bipolar disorder is associated with the highest rates of substance
      abuse of any psychiatric illness. Therefore, treatments that stabilize mood and
      decrease drug use or cravings are of great interest. Atypical antipsychotics are
      in widespread use in patients with bipolar disorder. However, minimal data are
      available on their use in bipolar patients with comorbid substance abuse.
      METHODS: Open-label, add-on, quetiapine therapy was examined for 12 weeks in 17
      outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated
      with a structured clinical interview; Hamilton Depression Rating (HDRS), Young
      Mania Rating (YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving
      Questionnaire (CCQ). Urine samples and self-reported drug use were also obtained.
      Data were analyzed using a last observation carried forward method on all
      subjects given medication at baseline. RESULTS: Significant improvement from
      baseline to exit was observed in HDRS, YMRS, BPRS and CCQ scores (p < or = 0.05).
      Dollars spent on cocaine and days/week of cocaine use decreased non
      significantly, and urine drug screens did not change significantly from baseline
      to exit. Quetiapine was well tolerated, with no subjects to our knowledge
      discontinuing because of side-effects. CONCLUSIONS: The use of quetiapine was
      associated with substantial improvement in psychiatric symptoms and cocaine
      cravings. The findings are promising and suggest larger controlled trials of
      quetiapine are needed in this population.

PMID- 12519102
TI  - Acute antimanic efficacy and safety of oxcarbazepine in an open trial with an on
      off-on design.
AB  - RATIONALE AND OBJECTIVES: Carbamazepine has shown reasonable antimanic
      properties, but its use has been limited because of enzyme-inducing effects. The
      keto-derivative oxcarbazepine (OXC) is very similar to carbamazepine, however,
      the metabolic pathway is different. OXC is not metabolized to the 10, 11-epoxide,
      which seems to be responsible for several undesirable side-effects of
      carbamazepine and furthermore OXC has less enzyme-inducing properties. METHODS:
      In this non-random open label study, patients were treated with OXC for 14 days,
      crossed over to no OXC for 7 days, and then crossed back over to OXC for the
      remaining 14 days. OXC was titrated to a final dose in a range of 900-2100 mg due
      to individual response. Treatment success was defined as a reduction of the
      original Young Mania Rating Scale (YMRS) score of more than 50% at the end of
      study period. RESULTS: Four of the 12 included patients (33%) met defined
      response criteria at the end of study period. Fifty percentage of the patients
      had to be prematurely excluded from the trial. The mean YMRS scores of the on
      periods were obviously different from the off-period. Forty-two percentage of the
      patients experienced side-effects leading to premature discontinuation in two of
      12 patients. CONCLUSION: Antimanic activity of OXC was demonstrated in this pilot
      study only for patients with mild or moderate manic symptoms. Further studies are
      encouraged to clarify OXC's role as mood-stabilizer and assess whether it has a
      profile similar to that of carbamazepine.

PMID- 12519103
TI  - Impact of concurrent alcohol misuse on symptom presentation of acute mania at
      initial evaluation.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of current alcohol
      misuse on symptom presentation of acute mania. METHODS: The impact of concurrent
      alcohol misuse on symptom presentation of acute mania was examined by comparing
      comorbid subjects with acute bipolar mania complicated by current alcohol misuse
      (n=60) with subjects with acute bipolar mania without current alcohol misuse
      (n=196). RESULTS: Age- and gender-controlled analysis revealed that the comorbid
      group presented with more severe psychopathology, as indicated by higher number
      of total mood-related symptoms as well as of higher total number of manic
      symptoms. Specifically, they presented with significantly higher rates of mood
      lability and impulsivity, and also demonstrated higher rates of violent behavior,
      and other drug use. CONCLUSIONS: Acute mania complicated by current alcohol
      misuse is differentiated from acute mania without alcohol misuse by the presence
      of higher numbers of manic symptoms and increased high risk behavior such as mood
      lability, impulsivity, violence, and other drug abuse.

PMID- 12519104
TI  - Factor V Leiden and factor II G20210A in preeclampsia and HELLP syndrome.
AB  - BACKGROUND: The association of factor V and factor II mutations with preeclampsia
      and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, and a
      possible role of the two thrombophilic mutations in the pathogenesis of the
      diseases have been previously investigated. The results, however, are still
      inconclusive and contradictory. METHODS: A case-control study was performed over
      an interval of 24 months, on 111 subjects with preeclampsia and 111 normal
      pregnant women matched for age and parity, without previous thromboembolic
      disorders. The subjects were tested for the mutation A1691G in the factor V gene
      (R506Q or Leiden mutation) and the mutation A20210G in the factor II
      (prothrombin) gene. The Student's t-test and the chi2-test were applied when
      appropriate, and odds ratios and 95% confidence intervals were calculated.
      RESULTS: Fourteen patients with preeclampsia (12.6%) had at least one of the two
      mutations, as compared with six controls (5.4%). Factor V Leiden was found in
      eight patients with preeclampsia (7.2%) and in five controls (4.5%). Factor II
      G20210A was detected in eight preeclamptic women (7.2%) and in one normal
      pregnant woman (0.9%)(p = 0.041). In the subgroup of 32 preeclamptic subjects
      with HELLP syndrome, factor V Leiden was found in three patients (9.3%) and
      factor II G20210A in two (6.2%). CONCLUSIONS: The prevalence of factor V and
      factor II mutations is increased in patients with preeclampsia; the thrombophilic
      mutations may interact with other pathogenic factors to determine the clinical
      features of the disease and of its complications.

PMID- 12519105
TI  - Causes and characteristics of maternal deaths in rural northern Tanzania.
AB  - BACKGROUND: To assess causes and characteristics of maternal deaths in a poorly
      characterized area. METHODS: A health facility- and population-based study, with
      an audit of case series on maternal deaths, was done in two divisions with 42
      villages (population 143 000), in Mbulu and Hanang districts, Arusha region,
      Tanzania. In 1995, all known deaths of women between 15 and 50 years, who were
      residents of the study area, were recorded from all the health facilities and
      villages in the study area. Supplementary data from the health facilities were
      collected in 1996. Verbal autopsies, health facility and antenatal records, and
      additional oral information were used to assess each maternal death. RESULTS:
      Forty-five maternal deaths were identified, 26 in 1995 and 19 in 1996. Thirteen
      of the deaths were direct, while 32 were indirect. Hemorrhage was the main cause
      of direct obstetric deaths and cerebral malaria of indirect death, accounting for
      20 cases, with most of them occurring during an epidemic season. Twenty-four of
      the women, including 10 of those dying of malaria, died postpartum. Most of the
      deceased women sought help at a health facility as the first place of seeking
      help, and used the hospital ambulance. Fourteen of the deaths (31%) were
      considered possibly avoidable under the prevailing circumstances, with delay in
      seeking help being most common. CONCLUSIONS: Addressing malaria as a major cause
      of maternal death, both in pregnancy and postpartum, in epidemic-prone areas, and
      increased community and family awareness of when to seek help could be important
      factors in reducing maternal deaths.

PMID- 12519106
TI  - Are recurrent pregnancies a risk in Type 1 diabetes?
AB  - OBJECTIVE: To assess the significance of recurrent pregnancies for the
      progression of Type 1 diabetes as well as the glycemic level and the occurrence
      of pre-eclampsia in consecutive pregnancies of the same Type 1 diabetic women.
      METHODS: A retrospective population-based birth cohort from the years 1986-95,
      comprising data of all (n = 210) Type 1 diabetic mothers and their 296 births in
      a geographically defined catchment area. Of the 125 primiparous women, 46 had
      their first two pregnancies during the study period. The courses of their first
      and second pregnancies were compared to determine the level of glycemic control
      and the occurrence and recurrence of complications, such as pre-eclampsia and
      aggravated retinopathy. The characteristics of the 53 women who remained
      primiparous were evaluated. RESULTS: Retinopathy was aggravated more often during
      the first pregnancy (95% CI 0.1-1.0), but its incidence did not increase further
      by the beginning of the second pregnancy. Pre-eclampsia complicated 16.9% of all
      pregnancies: it was more common during the first than second pregnancy (95% CI
      0.3-1.5) and its occurrence increased with the increasing severity of diabetes.
      Glycemic control was better in the second pregnancy, including both the
      periconceptional period (95% CI 0.7-2.8) and the later stages of pregnancy (95%
      CI 1.1-4.7). The women in the White classes F/R most often remained primiparous.
      CONCLUSIONS: Retinopathy was aggravated most often during the first pregnancy,
      but its infrequent occurrence in the second pregnancy reflects the reversible
      nature of these changes. The significance of the past pregnancy experience
      contributed to the increased tendency for optimal glycemic control in the second
      pregnancy.

PMID- 12519107
TI  - Trends in the management of the breech presentation at term; experience in a
      District General hospital over a 10-year period.
AB  - BACKGROUND: The recent evidence from a randomised controlled study on the
      management of breech delivery has settled the argument, however, this has not
      been to everybody's satisfaction. Elective delivery of all full term breech
      babies has implications. However, the trend seems to have been set long before
      the recent evidence, which is bound to accelerate the changes. MATERIALS AND
      METHODS: This is a retrospective observational study in a district general
      hospital. All planned term singleton (> or = 37 weeks gestation) breech
      deliveries between 1988 and 1997 were reviewed to assess changes in the
      management of the term breech delivery over a 10-year period. The main outcome
      measure was the trend of the intended mode of delivery correlated with the time
      period of the study and its effect on the neonatal and maternal outcome. RESULTS:
      There was a significant almost linear increase in the planned elective caesarean
      birth rate over the study period (OR = 1.25, 95% CI = 1.18-1.32). This was
      associated with a significant decline in neonatal intubation but no other effect
      on maternal or neonatal morbidity. There was no effect on perinatal mortality.
      CONCLUSIONS: Caesarean section has gradually become the preferred mode of
      delivery for the term breech presentation, despite prior lack of clinical
      evidence This change in trend may be influenced by maternal wishes. Reduced
      experience in the conduct of vaginal breech deliveries will have important
      implications for future obstetric specialists. A trial of vaginal delivery should
      be allowed in suitably selected cases before obstetricians lose the skills and
      confidence in performing an assisted vaginal breech delivery.

PMID- 12519108
TI  - Danish gynecologists' opinion about hysterectomy on benign indication: results of
      a survey.
AB  - AIMS: To survey Danish gynecologists' recommendations concerning hysterectomy and
      its method for benign diseases. METHODS: A questionnaire of seven clinical cases
      was sent to all gynecologists in Denmark (n = 450). The gynecologists were asked
      to recommend one of 14 possible treatments as the most appropriate for each case.
      In cases of hysterectomy the gynecologists were asked to rate the appropriateness
      of oophorectomy. Questions about age, employment, geographic area, sex of the
      gynecologist and preference of the hysterectomy method for themselves/their wives
      were included. RESULTS. THE RESPONSE RATE WAS: 73%. For women aged > or = 50
      years meno-metrorrhagia and symptomatic fibroids seemed to be important for
      hysterectomy recommendations, and for those aged < 50 years asymptomatic fibroids
      and unexplained pelvic pain seemed important for recommendation of other
      treatments. Employment, gender and geographic area influenced the recommendation
      of hysterectomy, and employment and geographic area only for the recommended
      method. Most of the gynecologists recommended the abdominal route and preferred
      the subtotal method. The gynecologists agreed on the recommendation concerning
      oophorectomy in cases of women aged under 46 years and over 55 years.
      Disagreement was found in cases of perimenopausal women. The gynecologists'
      preferences for hysterectomy methods did not differ from their recommendations
      for the cases. CONCLUSIONS: Agreement regarding the recommendation of
      hysterectomy was found in cases of postmenopausal metrorrhagia, while
      disagreement was found in cases of asymptomatic leiomyomas and unexplained pelvic
      pain. The gynecologists preferred the abdominal route and the subtotal
      hysterectomy method. Certain attributes of the gynecologists were found to be
      important to the recommendation of hysterectomy and its method.

PMID- 12519109
TI  - Comparative study of vaginal, laparoscopically assisted vaginal and abdominal
      hysterectomies for uterine myoma larger than 6 cm in diameter or uterus weighing
      at least 450 g: a prospective randomized study.
AB  - BACKGROUND: The purpose of this study was to compare peri-operative morbidity,
      preoperative sonographic estimation of uterine weight and postoperative outcomes
      of women with uterine fibroids larger than 6 cm in diameter or uteri estimated to
      weigh at least 450 g, undergoing either vaginal, laparoscopically assisted
      vaginal or abdominal hysterectomies. METHOD: Ninety patients who met the criteria
      of uterine fibroids larger than 6 cm by ultrasonographic examination were
      included in our prospective study. Patients were randomized into laparoscopic
      assisted vaginal hysterectomy (30 patients), vaginal hysterectomy (30 patients)
      and abdominal hysterectomy (30 patients) groups. RESULTS: The laparoscopically
      assisted vaginal hysterectomy group had significantly longer operative times than
      the abdominal and vaginal hysterectomy groups (109 +/- 22 min, 98 +/- 16 min, and
      74 +/- 22 min, respectively, p < 0.001). Blood loss for vaginal hysterectomy was
      significantly lower than for either abdominal or laparoscopically assisted
      vaginal hysterectomies (215 +/- 134 ml, 293 +/- 182 ml, and 343 +/- 218 ml,
      respectively, p = 0.04). Vaginal hysterectomy and laparoscopically assisted
      vaginal hysterectomy groups had shorter hospital stays, lower postoperative pain
      scores, more rapid bowel recovery and lower postoperative antibiotic use than the
      abdominal hysterectomy group. Uterine weight in the abdominal hysterectomy group
      was significantly heavier than in the vaginal and laparoscopically assisted
      vaginal hysterectomy groups (1020 +/- 383 g, 835 +/- 330 g, and 748 +/- 255 g,
      respectively, p = 0.02). We estimated that when a myoma measured between 8 and 10
      cm, the uterus weighed approximately 450 g, and the sensitivity of this
      prediction was 57.5%. For a myoma larger than 13 cm, the estimated uterine weight
      was more than 900 g and the sensitivity of this prediction was 71%. CONCLUSION:
      The study shows vaginal hysterectomy and laparoscopically assisted vaginal
      hysterectomy can be performed in women with uterine weight of at least 450 g.
      Preoperative ultrasonographic examination can provide the surgeon with valuable
      information on the size of the fibroid and the estimated weight of the enlarged
      uterus before implementing a suitable surgical method.

PMID- 12519110
TI  - Ectopic pregnancy revisited in Benin City, Nigeria: analysis of 152 cases.
AB  - BACKGROUND: Ectopic pregnancy is still a major health problem among women of
      childbearing age in our community. The majority of the patients with ectopic
      pregnancy are nulliparous in their mid twenties, with previous induced
      abortion(s) and or pelvic inflammatory disease. It remains a major challenge to
      the reproductive performance of women worldwide. OBJECTIVE: The study is an
      analysis of the clinical profile of patients presenting with ectopic pregnancy,
      to investigate the current status of the incidence, predisposing risk factors and
      the management options available in Benin. MATERIALS AND METHODS: One hundred and
      fifty two cases of ectopic pregnancies managed at the University of Benin
      Teaching Hospital (UBTH) between January 1994 and December 1998 were analyzed.
      Clinical and socio-biological information were retrieved from patients' case
      notes, and supplemented by information from the operating theatre and ward
      registers. RESULTS: The incidence of ectopic pregnancy during this study period
      was 1. 68% of total births and 6.74% of and gynecologic admissions. Nulliparous
      patients were 49.3%, while the peak age of incidence was 20-25 years. 95/152
      (62.5%) of the patients had previous induced abortion(s), while pelvic adhesions
      were noted in 62/152 (40.85 approximately %). 67.8% of the patients were not
      using any method of contraception, while 13.8% and 9.2% were using lUD and
      barrier methods, respectively. Abdominal pain, 2 degrees amenorrhoea and
      irregular vaginal bleeding (83.6%, 77.5% and 73.7%, respectively) were the most
      frequent presenting complaints. 75/152 of the patients (49.3%) were in a state of
      shock, and 80.3% had ruptured tubal pregnancy at presentation. All patients had
      laparotomy, 54.6% and 34.9% had right and left salpingectomy, respectively.
      831/52 of the patients (54.6%) had autotransfusion during surgery. CONCLUSION: In
      Benin, the majority of the patients with ectopic pregnancy are nulliparous in
      their mid twenties, with history of previous induced abortion(s) and or pelvic
      inflammatory disease. Management option is limited to laparotomy and
      salpingectomy.

PMID- 12519111
TI  - Multivariate analysis of histopathologic prognostic factors for invasive cervical
      cancer treated with radical hysterectomy and systematic retroperitoneal
      lymphadenectomy.
AB  - BACKGROUND: The aim of this study was to identify the independent histopathologic
      prognostic factors for patients with cervical carcinoma treated with radical
      hysterectomy including paraaortic lymphadenectomy. METHODS: A total of 187
      patients with stage IB to IIB cervical carcinomas treated with radical
      hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively
      analyzed. The median follow-up period was 83 months. Cox regression analysis was
      used to select independent prognostic factors. RESULTS: Using multivariate Cox
      regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic
      nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis),
      histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and
      histology of pure adenocarcinoma were found to be independently related to
      patients' poor survival. For patients who had a tumor histologically confined to
      the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI
      was the most important prognostic factor, and histologic type, depth of cervical
      stromal invasion, and tumor size were not related to survival. The survival of
      patients with a tumor extending to parametrium or pelvic lymph node(s) was
      adversely affected by histology of pure adenocarcinoma. When the tumor extended
      to common iliac or paraaortic nodes, patients' survival became quite poor
      irrespective of LVSI or histologic type of pure adenocarcinoma. Patients'
      prognosis could be stratified into low risk (patients with a tumor confined to
      the uterus not associated with LVSI: n = 80), intermediate risk (patients with a
      tumor confined to the uterus associated with positive LVSI, and patients with
      squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or
      parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma
      associated with pelvic lymph node metastasis or parametrial invasion, and
      patients with common iliac/paraaortic node metastasis: n = 21) with an estimated
      5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/-
      9.7%, respectively. CONCLUSIONS: LN status, parametrial invasion, LVSI, and
      histology of pure adenocarcinoma are important histopathologic prognostic factors
      of cervical carcinoma treated with radical hysterectomy and systematic
      retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma
      may be stratified by combined analysis of these histopathologic prognostic
      factors. Postoperative therapy needs to be individualized according to these
      prognostic factors and validated for its efficacy using randomized clinical
      trials.

PMID- 12519112
TI  - Hormone levels in pre-eclampsia.

PMID- 12519114
TI  - Heat versus drugs in the treatment of benign prostatic hyperplasia.
AB  - The improvement in symptoms and voiding function is greater with transurethral
      microwave thermotherapy than with drug therapy, and the associated morbidity is
      low. Transient urinary retention necessitating catheterization is of short
      duration after targeted microwave thermotherapy. The short-term effect of
      microwave thermotherapy can be improved by neoadjuvant and adjuvant alpha
      blockade. Microwave treatment offers greater versatility than drug therapy,
      allowing patients with severe baseline symptoms and small prostates to be treated
      successfully. Medical management improves symptoms to a more modest extent than
      does microwave treatment. Finasteride gives comparatively small symptom and flow
      rate improvements and requires several months for the maximum responses. With
      alpha-blockers the onset of action is fast and side-effects reversible, although
      they limit their utility. Finasteride or alpha-blockers must be continued
      indefinitely to maintain improvements in patients with BPH, but they have a
      favourable safety and tolerability profile.

PMID- 12519115
TI  - Ureteric reconstruction.
AB  - Although the ureter is functionally simply a tube to transport urine, ureteric
      surgery requires detailed anatomical knowledge and advanced surgical skills,
      because the ureter has a delicate blood supply. Therefore, the urological surgeon
      must have distinct strategies available to bridge ureteric defects of various
      sites and lengths. Furthermore, handling during and after surgery should be
      individualized to the patient's pre- and intraoperative situation. In this
      review, the indications for reconstruction of a specific ureteric defect, the
      required techniques and postoperative recommendations are discussed.

PMID- 12519116
TI  - Metabolic and functional consequences of urinary reconstruction with bowel.

PMID- 12519117
TI  - Current approaches to assessing the quality of life in children and adolescents.
AB  - Urologists are well aware of the importance of the quality of life (QoL) in
      determining the success of their treatments. The public are increasingly aware of
      this aspect of medicine. The advent of fetal ultrasonography has made knowledge
      of QoL in long-term survivors of congenital anomalies essential in counselling
      about pregnancy termination. It is becoming mandatory that clinical trials
      involving adults include an assessment of QoL. For children, measuring QoL has
      been restricted to life-threatening conditions such as cancer or transplantation
      medicine. Measuring QoL is difficult in children and adolescents, and this is
      reflected in the few suitable instruments available. The development of sexuality
      contributes a further difficulty as many anxieties typical of those with genital
      anomalies may be common to all teenagers. Several instruments rely on the
      opinions of a proxy (parent or carer) but self-assessment by the child is
      preferable where possible. The need for child self-assessment is supported by
      finding little concordance between child and proxy assessments. While measuring
      QoL is challenging, we provide a substantial case for greater consideration of
      QoL in paediatric urology.

PMID- 12519120
TI  - Regulation of yellow pigment formation in mice: a historical perspective.
AB  - Pigment synthesis by hair follicle melanocytes is modulated by a large number of
      environmental and genetic factors, many of which are discussed in this review.
      Eumelanic (non-yellow) pigment is produced by hair follicle melanocytes following
      the binding of alpha-melanocyte stimulating hormone to melanocortin receptor 1.
      Binding of this hormone to the melanocyte membrane is blocked by agouti signaling
      protein (ASP) which is encoded by the agouti locus and results in the synthesis
      of yellow pigment, instead of non-yellow (black/brown) pigment. The cyclical
      release of ASP by hair follicle cells results in a black/brown hair with a
      subapical yellow band. This is the wild-type coat color pattern of many mammals
      and is called agouti. Several dominant mutations at the agouti locus in mice,
      induced by retrotransposon-like intracisternal A particles, result in ectopic
      over-expression of ASP and animals with much higher proportions of all-yellow
      hairs. This abnormal presence of ASP in essentially all body cells results in the
      'yellow agouti obese mouse syndrome.' The obesity has been associated with
      binding of ASP to melanocortin receptor 4 inactivating the latter. The syndrome
      also includes hyperinsulinemia, increased somatic growth, and increased
      susceptibility to hyperplasia and carcinogenesis. The physiologic and molecular
      bases for these syndrome components have not yet been elucidated. This
      historically orientated review is subdivided, where applicable, into pre- and
      post-1992 subsections to emphasize the impact of the cloning of the agouti and
      extension loci and their protein products on the identification of the molecular
      and physiological pathways modulating the manifold aspects of pheomelanogenesis.

PMID- 12519121
TI  - Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate
      experimental access to UV initiating events.
AB  - Cutaneous malignant melanoma, the most lethal of the skin cancers, known for its
      intractability to current therapies, continues to increase in incidence,
      providing a significant public health challenge. There is a consensus that skin
      cancer is initiated by sunlight exposure. For non-melanoma skin cancer there is
      substantial evidence that chronic exposure to the ultraviolet B radiation (UVB)
      (280-320 nm) portion of the sunlight spectrum is responsible. Experimentally, UVB
      is mutagenic and chronic UVB exposure can cause non-melanoma skin cancer in
      laboratory animals. Non-melanoma tumors in animals and in humans show
      characteristic UVB signature lesions in the tumor suppressor p53 and/or in the
      patched (PTCH) gene. An action spectrum or wavelength dependence for squamous
      cell carcinoma in the mouse shows a major peak of efficacy in the UVB. For
      malignant melanoma, however, the situation is unclear and the critical direct
      target(s) of sunlight in initiating melanoma and even the wavelengths responsible
      are as yet unidentified. This lack of information is in major part a result of a
      paucity of animal models for melanoma which recapitulate the role of sunlight in
      initiating this disease. The epidemiology of melanoma differs significantly from
      non-melanoma skin cancer. Intense sporadic sunlight exposure in childhood,
      probably exacerbated by additional adult exposure, is associated with elevated
      melanoma risk. Melanoma is also a disease of gene-environment interactions with
      underlying genetic factors playing a significant role. These major differences
      indicate that extrapolation from information for non-melanoma skin cancer to
      melanoma is unlikely to be useful. We summarize in this review the experimental
      information available on the role of UV radiation in melanoma and give an
      overview of animal melanoma models. A new model derived by neonatal UV
      irradiation of hepatocyte growth factor/scatter factor (HGF/SF) transgenic mice
      is described which recapitulates the etiology, the histopathology and molecular
      pathogenesis of human disease. It is anticipated that the HGF/SF transgenic model
      will provide a means to access the mechanism(s) by which sunlight initiates this
      lethal disease and provide an appropriate vehicle for derivation of appropriate
      therapeutic and preventive strategies.

PMID- 12519122
TI  - Stimulation of melanogenesis by tetradecanoylphorbol 13-acetate (TPA) in mouse
      melanocytes and neural crest cells.
AB  - In vitro studies have shown that the phorbol ester, 12-tetradecanoylphorbol 13
      acetate (TPA) induces neural crest cell differentiation into melanocytes, and
      stimulates proliferation and differentiation of normal melanocytes. As TPA is not
      a physiological agent, its action is clearly mimicking some in vivo pathway
      involved in these processes. An understanding of the effect of TPA on the
      expression of melanogenic genes will therefore provide valuable insight into the
      molecular mechanisms regulating melanocyte differentiation. In this study, we
      utilized primary cultures of neural crest cells and an immortalized melanocyte
      cell line (DMEL-2) which proliferates in the absence of TPA, to explore the
      effects of TPA on key melanogenic effectors. In neural crest cells, TPA was found
      to be necessary for both microphthalmia associated transcription factor (Mitf) up
      regulation and for melanin synthesis. Using northern blots, we show that in DMEL
      2 cells, TPA significantly increases the messenger ribonucleic acid (mRNA) levels
      of the tyrosinase gene family (tyrosinase, Tyrp1 and Dct) and the expression of
      Mitf. Western blots demonstrate that in these TPA-treated cells there is a
      concomitant increase in Tyr, Tyrp1 and glycosylated Dct protein levels. Pax3, a
      known Mitf regulator, is unaltered by TPA treatment. This study demonstrates the
      utility of a novel cell line for investigating the long-term effects of TPA on
      melanogenesis and provides an understanding of how TPA enhances mouse melanocyte
      differentiation.

PMID- 12519123
TI  - Ethnic variation in tyrosinase and TYRP1 expression in photoexposed and
      photoprotected human skin.
AB  - The relative expression of a number of key mediators of human pigmentation
      including tyrosinase, tyrosinase related protein-1 (TYRP1), endothelin-1 and
      adrenocorticotrophic hormone (ACTH) proteins were analysed and quantified in
      immunohistochemically stained skin sections using semiquantitative computer
      assisted image analysis. Comparisons were made between a range of different
      ethnic skin types including European, Chinese, Mexican, Indian and African at
      both chronically photoexposed and photoprotected sites. Melanocyte number varied
      little with ethnicity except in the European group which had 60-80% more
      melanocytes than other skin types (P < 0.01, n = 10; Student Neuman-Keuls).
      However, melanocyte number was increased approximately twofold in chronically
      photoexposed skin of all ethnic groups (P < 0.001, n = 48; paired t-test).
      Tyrosinase protein expression in melanocytes did not vary with ethnicity, but
      TYRP1 protein was significantly elevated (approximately 2.6-fold) in darkly
      pigmented African and Indian skin types compared with lightly pigmented Mexican,
      Chinese and European skin types. In melanocytes from chronically photoexposed
      skin, there was a modest but significant increase in the expression of tyrosinase
      protein (approximately 1.2-fold, P < 0.001, n = 48; paired t-test), together with
      a significant and slightly larger increase in the expression of TYRP1 protein
      (approximately 1.6-fold, P < 0.005, n = 48; paired t-test). In contrast, the
      expression of endothelin-1 and ACTH showed no significant variation with either
      ethnicity or photoexposure. These data are consistent with the view that
      maintenance of a chronically hyperpigmented phenotype in chronically photoexposed
      human skin is largely the result of a stable increase in the number of tyrosinase
      positive melanocytes at these sites. Moreover, the observed ethnic variation in
      TYRP1 protein expression suggests that TYRP1 may play a significant role in
      mediating ethnic differences in melanogenesis and constitutive skin pigmentation
      in vivo.

PMID- 12519124
TI  - Transcription of prostanoid receptor genes and cyclooxygenase enzyme genes in
      cultivated human iridial melanocytes from eyes of different colours.
AB  - Several prostaglandin analogues used for glaucoma treatment have been shown to
      cause increased iridial pigmentation as side-effect. In the present study we
      identified the types of prostanoid receptors and cyclooxygenase (COX) enzymes
      that are expressed in human iridial melanocytes isolated from eyes of different
      colours. Iris specimens were obtained during trabeculectomy surgery, or from
      enucleated eyes, and the iridial melanocytes were isolated and cultivated. The
      transcription of the DP, EP1, EP2, EP3, EP4, FP, IP and TP prostanoid receptor
      genes as well as the COX-1 and COX-2 enzyme genes was investigated using reverse
      transcriptase-polymerase chain reaction (RT-PCR). Of the prostanoid receptors the
      FP receptor gene was found to be most consistently transcribed in the melanocytes
      isolated from both blue- and hazel-coloured eyes. No RNA of the DP, EP2 and TP
      receptor genes could be detected, whereas the EP1, EP3, EP4 and IP receptor genes
      were found to be transcribed in melanocytes from some eyes. The COX-2 gene was
      found to be transcribed, but the COX-1 gene less consistently. There was no
      difference in gene transcription pattern between melanocytes originating from
      eyes treated with latanoprost, and eyes not previously treated with the
      prostaglandin. These results indicate that the FP prostanoid receptor gene is
      transcribed in cultivated human iridial melanocytes of both blue and hazel eyes,
      whereas the other prostanoid receptor genes seem to be transcribed much less
      frequently, or not at all. Surprisingly, the COX-2 rather than the COX-1 gene,
      was found to be transcribed in the melanocytes.

PMID- 12519125
TI  - Xanthophore migration from the dermis to the epidermis and dermal remodeling
      during Salamandra salamandra salamandra (L.) larval development.
AB  - During larval development of Salamandra salamandra salamandra chromatophores
      organize to form the definitive pigment pattern constituted by a black background
      with yellow patches that are characterized by epidermal xanthophores and dermal
      iridophores. Simultaneously the dermis undergoes remodeling from the larval stage
      to that typical of the adult. In the present study we ultrastucturally and
      immunocytochemically examined skin fragments of S. s. salamandra larvae and
      juveniles in order to investigate the modalities of xanthophore migration and
      differentiation in the context of dermal remodeling from the larval to adult
      stage. Semithin and thin sections showed that the dermis in newly born larvae
      consists of a compact connective tissue (basement lamella), to which fibroblasts
      and xanthophores adhere, and of a loose deep collagen layer. As larval
      development proceeds, fibroblasts and xanthophores invade the basement lamella,
      skin glands develop and the adult dermis forms. At metamorphosis, xanthophores
      reach the epidermis crossing through the basal lamina. We examined
      immunocytochemically the expression of signal molecules, such as fibronectin,
      vitronectin, beta1-integrin, chondroitin sulfate, E-cadherin, N-cadherin and
      plasminogen activator, which are known to be involved in regulating morphogenetic
      events. Their role in dermal remodeling and in pigment pattern formation is
      discussed.

PMID- 12519126
TI  - Noradrenaline- and melatonin-mediated regulation of pigment aggregation in fish
      melanophores.
AB  - The effects of melatonin and noradrenaline (NA) on bi-directional melanosome
      transport were analysed in primary cultures of melanophores from the Atlantic
      cod. Both agents mediated rapid melanosome aggregation, and by using receptor
      antagonists, melatonin was found to bind to a melatonin receptor whereas NA binds
      to an alpha2-adrenoceptor. It has previously been stated that melatonin-mediated
      melanosome aggregation in Xenopus is coupled with tyrosine phosphorylation of a
      so far unidentified high molecular weight protein and we show that although
      acting through different receptors and through somewhat different downstream
      signalling events, tyrosine phosphorylation is of the utmost importance for
      melanosome aggregation mediated by both NA and melatonin in cod melanophores.
      Together with cyclic adenosine 3-phosphate-fluctuations, tyrosine phosphorylation
      functions as a switch signal for melanosome aggregation and dispersion in these
      cells.

PMID- 12519127
TI  - Agouti signal protein regulation in human melanoma cells.
AB  - Production of the pigment eumelanin is controlled by alpha-melanocyte stimulating
      hormone (alpha-MSH) stimulation of melanocortin 1 receptor (Mc1r), whereas
      production of pheomelanin results from agouti antagonism of alpha-MSH signalling
      through Mc1r. The role of agouti in mouse pigmentation has been extensively
      investigated but a role for agouti signalling protein (ASIP) in human
      pigmentation has not been determined. To determine whether ASIP regulates known
      melanogenic genes in humans, ASIP was over-expressed in a human melanoma cell
      line. Levels of mRNA and protein were measured in genes known to be up or down
      regulated by agouti in the mouse, namely microphthalmia (Mitf), tyrosinase (Tyr),
      tyrosinase-related protein 1 (Tyrp1), dopachrome tautomerase (Dct), Mc1r, silver,
      initiation transcription factor 2 (Itf2) and mini chromosome maintenance protein
      6 (Mcm6). These melanogenic genes were not found to be significantly up or down
      regulated by ASIP at the transcriptional level in human melanoma cells. However,
      ASIP down-regulation of tyrp1 was observed at the translational level. To
      identify novel genes that may be regulated by ASIP in melanoma cells, microarrays
      were used to determine differences in gene expression between the control and
      ASIP transfected melanoma cells. The expression level of human RNAs were
      determined by microarray analysis using a 19,200 cDNA and a 19,200
      oligonucleotide array representing 13,000 and 18,864 individual genes,
      respectively. Genes observed to be modulated by ASIP were confirmed by
      quantitative real-time polymerase chain reaction. Results identify five genes,
      namely PPARbeta, eIF-4B, RRM2, MINOR and EVI2B that are down-regulated by ASIP,
      indicating a likely role for ASIP in human melanogenesis.

PMID- 12519128
TI  - The effect of preparation procedures on the morphology of melanin from the ink
      sac of Sepia officinalis.
AB  - The structure of melanin extracted from the ink sac of the cuttlefish Sepia
      officinalis was examined for different methods of isolation and purification of
      the pigment. Scanning electron microscopy (SEM) images of Sepia eumelanin
      prepared by different procedures establish that multi-microm-sized aggregates
      reported by previous workers are generated by their sample preparation, and that
      the dominant constituents of Sepia melanin are approximately 150 nm spherical
      granules. Brunauer-Emmett-Teller (BET) measurements reveal that Sepia eumelanin
      from Sigma (prepared by spray drying the pigment) has a surface area of 14.3
      m2/g. Pigment extracted directly from the fresh ink sac and then freeze-dried has
      a surface area of 21.5 m2/g, while CO2-supercritically dried has a surface area
      of 37.5 m2/g. This is consistent with SEM images showing that the process of
      freeze-drying produces aggregates, but to a lesser extent than spray drying.
      Supercritical drying of the sample produces suspensions of the individual
      approximately 150 nm granule, which is more reflective of the natural pigment.
      Brunauer-Emmett-Teller surface area analysis and Barrett-Joyner-Halenda (BJH)
      pore volume analysis indicate that the surface of the granules is not smooth and
      the interior of the granules is not porous, but rather the aggregates of granules
      are porous. Ultra-high resolution SEM and atomic force microscopy (AFM) images
      show the granules are easily deformed and are comprised of smaller constituents.
      De-aggregation of the granules by sonication and ultra-filtration reveal a range
      of structures depending on the pore size of the membrane used. The implications
      of these results on quantifying photochemical properties and kinetic reaction
      rate constants of melanin are discussed.

PMID- 12519132
TI  - Use of caudal-epidural opioids in children: still state of the art or the
      beginning of the end?

PMID- 12519129
TI  - Effects of melanogenesis-inducing nitric oxide and histamine on the production of
      eumelanin and pheomelanin in cultured human melanocytes.
AB  - Melanin pigments produced in human melanocytes are classified into two
      categories; black coloured eumelanin and reddish-yellow pheomelanin. Stimulation
      of melanocytes with alpha-melanocyte-stimulating hormone (alpha-MSH), one of
      several melanogenic factors, has been reported to enhance eumelanogenesis to a
      greater degree than pheomelanogenesis, which contributes to hyperpigmentation in
      skin. Nitric oxide (NO) and histamine are also melanogenesis-stimulating factors
      that are released from cells surrounding melanocytes following ultraviolet (UV)
      irradiation. In this study, the effects of NO and histamine on the ratio of
      eumelanin and pheomelanin were examined in human melanocytes, and then compared
      with that of alpha-MSH. The amounts of eumelanin and pheomelanin were quantified
      using high-performance liquid chromatography analysis after oxidation and
      hydrolysis of melanin. Melanogenesis was induced by the addition of alpha-MSH,
      NO, or histamine to melanocytes. The amount of eumelanin production significantly
      increased with independent stimulation by these melanogenic factors, especially
      histamine, while that of pheomelanin significantly increased with alpha-MSH and
      NO, but only slightly with histamine. As a result, the ratio of eumelanin and
      pheomelanin increased significantly with the addition of NO or histamine. These
      results suggest that NO and histamine, as in the case of alpha-MSH, may
      contribute to UV-induced hyperpigmentation by enhancing eumelanogenesis.

PMID- 12519133
TI  - Childhood obesity: a challenge for the anaesthetist?
AB  - The definition of childhood obesity has not been standardized in the past, making
      studies difficult to compare. In spite of this, the increase in the incidence of
      childhood obesity is evident and has now reached epidemic proportions. Obese
      children experience few of the medical complications seen in obese adults.
      Respiratory physiology appears to be most affected, the degree of which is
      determined by the level of obesity. Although there is a considerable amount of
      information on the anaesthetic management of the obese adult, very little has
      been written concerning the obese child. There is less pathology in the obese
      child when compared with the adult but some evidence shows a higher likelihood of
      a critical incident occurring when anaesthetizing such children. This shows that
      we need to be as worried about anaesthetizing the obese child as we are for the
      obese adult. This concern should increase with increasing body mass index.

PMID- 12519134
TI  - Risk factors for airway complications during general anaesthesia in paediatric
      patients.
AB  - BACKGROUND: Although airway complications are a frequent problem during
      paediatric anaesthesia, no study has prospectively identified risk factors for
      adverse respiratory events during airway management when LMA trade mark
      (laryngeal mask airway), face mask (FM) or a tracheal tube (TT) are used.
      METHODS: A prospective study was performed at a university hospital's paediatric
      centre. Preoperative information included recent history of respiratory infection
      and type of surgery. Intraoperative information included the identification of
      the device user, the duration of anaesthesia and the type of airway device used.
      Adverse respiratory events during the perioperative and postoperative periods
      were registered. One thousand nine hundred and ninety-six patients were included
      (mean age 6.45 +/- 2.9 years). RESULTS: Airway complications occurred in 10.2% of
      the patient for LMA (72/704), 4.7% for FM (19/401) and 7.4% (66/891) for TT.
      Using a stepwise logistic regression, three independent risk factors were
      identified: age < 6 years, odds ratio (OR) 1.84, 95% CI (1.21-2.80); use of LMA,
      OR 2.32, 95% CI (1.29-4.17); presence of respiratory infections (RI) before the
      procedure, OR 3.72, 95% CI (2.3-5.99). CONCLUSIONS: Age < 6 years, recent RI and
      the use of the LMA were identified as independent factors associated with an
      increased risk of airway complications.

PMID- 12519135
TI  - Repeated administration of ketamine may lead to neuronal degeneration in the
      developing rat brain.
AB  - BACKGROUND: This study was conducted to investigate, in vivo, the dose and
      duration effects of ketamine administration on neuronal degeneration in the
      developing rat brain. METHODS: Seven-day-old (P7) Sprague-Dawley rats were
      treated with intraperitoneal injections of ketamine, a noncompetitive N-methyl-D
      aspartate receptor antagonist. Degenerating neurones were identified by the
      cupric-silver stain from 10 brain regions using the stereological disector
      method. RESULTS: A single dose of ketamine (25, 50 and 75 mg.kg-1) did not
      increase neuronal degeneration compared with the saline-treated control. However,
      repeated doses of ketamine (25 mg.kg-1) at 90-min intervals over 9 h increased
      degenerating neurones in seven out of 10 brain regions. CONCLUSIONS: These
      findings suggest that the duration of ketamine exposure correlates with increased
      neuronal degeneration in the developing rat brain.

PMID- 12519136
TI  - Anaesthesia with sevoflurane in children: nitrous oxide does not increase
      postoperative vomiting.
AB  - BACKGROUND: Nitrous oxide (N2O) has been associated with postoperative nausea and
      vomiting (PONV), but some studies show conflicting data. The aim of this study
      was to assess whether the combination of N2O/sevoflurane, in paediatric general
      anaesthesia, increases the incidence of vomiting in the 24 h following surgery
      compared with sevoflurane alone. METHODS: One hundred and fourteen children, aged
      1-10 years, who underwent testicle and inguinal hernia surgery, were randomized
      to receive one of the following two anaesthetic regimens: sevoflurane with 70%
      N2O (group A) or sevoflurane alone (group B). RESULTS: No significant differences
      were observed in the incidence of postoperative vomiting between the two groups.
      The overall incidence of postoperative vomiting was 14.9%; 14.3% in group A and
      15.5% in group B (P=0.9). CONCLUSIONS: Nitrous oxide used in combination with
      sevoflurane is not associated with an increase in the incidence of emesis in
      children who undergo testicle and inguinal hernia procedures.

PMID- 12519137
TI  - Infusion technology: a cause for alarm.
AB  - BACKGROUND: [corrected] Volumetric infusion pumps are widely used in paediatric
      practice. Tissue extravasation is a hazard. The occlusion pressure limit alarm,
      although not intended to detect extravasation, is the only warning sign present
      to indicate flow faults in the infusion systems. METHODS: Extravasations were
      created in the subcutaneous plane of 20 limbs of five piglets with normal saline
      via an infusion pump. Five flow rates were used with each piglet allocated to
      one: 100 ml.h-1, 200 ml.h-1, 300 ml.h-1, 400 ml.h-1, 500 ml.h-1. The occlusion
      pressure limit was first set at low and adjusted to medium, then to high, upon
      alarm activation. Line pressure at 5-min intervals and upon alarm activation and
      volume of infusate given were measured. Limb diameters before and after infusion
      were measured. RESULTS: Six out of 20 cases failed to activate any alarm. The
      low, medium and high occlusion pressure limit alarms were activated in 14, 1 and
      0 instances, respectively. The incidence of alarm activation is higher in the
      forelimb compared with the hindlimb (P=0.001). The tissue compliance and volume
      infused at alarm activation are significantly lower in the former (P < 0.05).
      Line pressure increases with increase in flow rates for the same limb (P=0.013
      Fore, P=0.005 Hind). CONCLUSIONS: Occlusion pressure limit alarm cannot reliably
      detect extravasation especially at sites with high compliance, low flow rates,
      even at low occlusion limit. Line pressure depends on interplay of site
      (compliance) and flow rate and is independent of volume extravasated. Users must
      be aware of the set occlusion pressure limit. Repeated clinical assessment
      remains vital.

PMID- 12519138
TI  - Effect of route of buprenorphine on recovery and postoperative analgesic
      requirement in paediatric patients.
AB  - BACKGROUND: We compared the effects of extradural with intravenous (i.v.)
      buprenorphine on postoperative pain and recovery characteristics. METHODS: Thirty
      patients, aged 11-13 years, who were undergoing inguinal hernia repair with or
      without orchidopexy, were randomly allocated to receive either caudal 0.5%
      bupivacaine alone (group A) or were additionally given i.v. buprenorphine 2.5
      micro g.kg-1 (group B) or caudal buprenorphine in the same dose (group C).
      Patients were followed for 8 h after the end of surgery. RESULTS: All patients
      remained haemodynamically stable during the study period and no clinical
      respiratory depression was seen. Nausea, vomiting, urinary retention and pruritus
      were more common in the extradural buprenorphine group. Three patients in group
      A, five in group B and eight in group C did not require any additional analgesia
      during the study period. The incidence of vomiting was 20%, 50% and 80% in groups
      A, B and C, respectively. Four patients in group C had urinary retention compared
      with one each in the other two groups. CONCLUSIONS: Administration of
      buprenorphine resulted in a higher incidence of side-effects.

PMID- 12519139
TI  - Effect of ilioinguinal nerve block on the catecholamine plasma levels in
      orchidopexy: comparison with caudal epidural block.
AB  - BACKGROUND: Both caudal epidural and ilioinguinal/iliohypogastric nerve blocks
      have been used to provide effective intra- and postoperative analgesia. Stress
      response hormone levels can be used as an objective method to assess the
      analgesic efficacy of the anaesthetic techniques used in infraumbilical surgery
      in children. In this study, we compared catecholamine blood levels in children
      undergoing these two different supplementary analgesic/anaesthetic techniques.
      METHODS: Thirty male paediatric patients undergoing orchidopexy, ASA I, received
      inhalation general anaesthesia, and were randomly allocated to one of two groups:
      a caudal group (n = 15) and an ilioinguinal/iliohypogastric nerve block group (n
      = 15). Plasma epinephrine and norepinephrine concentrations were measured at the
      induction time, at the end of surgery, and in the postanaesthesia care unit.
      Postoperative pain score was also assessed in the postanaesthesia care unit.
      RESULTS: In both groups, there was a substantial decrease in the catecholamine
      blood levels; however, there were significantly higher levels of epinephrine in
      the ilioinguinal group at the end of surgery (P = 0.008) and in the recovery room
      (P = 0.02) and a significant higher level of norpinephrine in the recovery room
      (P = 0.008). CONCLUSIONS: The result of this study revealed that caudal epidural
      block was more effective than ilioinguinal block in suppressing the stress
      response as reflected in epinephrine and norepinephrine blood levels in
      orchidopexy patients.

PMID- 12519140
TI  - Life threatening tension pneumoperitoneum from intestinal perforation during air
      reduction of intussusception.
AB  - We present a case report of a child with intussusception who underwent air
      reduction which was complicated by bowel perforation. Life threatening tension
      pneumoperitoneum developed rapidly and immediate needle decompression was life
      saving in this case. The pathophysiology of hyperacute abdominal compartment
      syndrome is discussed.

PMID- 12519141
TI  - Difficult paediatric intubation when fibreoptic laryngoscopy fails.
AB  - We report an unusual problem with fibreoptic bronchoscopy in an 8-year-old girl
      with Negar syndrome. She had a history of difficult airway since birth, and had
      undergone mandibular distraction for severe obstructive sleep apnoea when she was
      aged 2 years. Nagar syndrome is a Treacher-Collins like syndrome with normal
      intelligence, conductive bone deafness and problems with articulation. The
      patients have malar hypoplasia with down slanting palpebral fissures, high nasal
      bridge, micrognathia, absence of lower eyelashes, low set posteriorly rotated
      ears, preauricular tags, atresia of external ear canal, cleft palate, hypoplasia
      of thumb, with or without radius, and limited elbow extension. Protracted
      attempts with a fibreoptic bronchoscope failed to visualize the glottis, and this
      was only possible when the tube was guided to the larynx by blind nasal
      intubation. Apparently, the healing of the wounds for the mandibular distraction
      in the mandibular space on the inside of the rami of the mandible had caused
      differential fibrosis on either side of the hyoid, leading to a triplane
      distortion of the larynx with a left shift, clockwise rotation to a 2-8 o'clock
      direction and a slight tilt towards the left pharyngeal wall. The large
      epiglottis overlying this had precluded a view of the larynx. Finally, the older
      technique of breathguided intubation facilitated fibreoptic bronchoscopy to
      achieve tracheal intubation.

PMID- 12519142
TI  - Niemann-Pick disease: a rare problem in anaesthesiological practice.
AB  - We describe the problems encountered during general anaesthesia in a 2-year-old
      boy who was suffering from an extremely severe form of Niemann-Pick disease.
      Attention focused on respiratory difficulties and intubation problems. The
      usefulness of the lateral position and the limits of the Mallampati score in this
      case are discussed.

PMID- 12519143
TI  - Hydrothorax: a life threatening complication during thoracotomy.

PMID- 12519144
TI  - Cytochrome P450 pharmacogenetics and anaesthesia.

PMID- 12519145
TI  - Severe back pain post caudal injection.

PMID- 12519146
TI  - Oral granisetron revisited.

PMID- 12519183
TI  - The identification of circular extrachromosomal DNA in the nuclear genome of
      Trypanosoma brucei.
AB  - Nuclear extrachromosomal DNA elements have been identified in several
      kinetoplastids such as Leishmania and Trypanosoma cruzi, but never in Trypanosoma
      brucei. They can occur naturally or arise spontaneously as the result of
      sublethal drug exposure of parasites. In most cases, they are represented as
      circular elements and are mitotically unstable. In this study we describe the
      presence of circular DNA in the nucleus of Trypanosoma brucei. This novel type of
      DNA was termed NR-element (NlaIII repeat element). In contrast to drug-induced
      episomes in other kinetoplastids, the T. brucei extrachromosomal NR-element is
      not generated by drug selection. Furthermore, the element is stable during
      mitosis over many generations. Restriction analysis of tagged NR-element DNA,
      unusual migration patterns during pulsed field gel electrophoresis (PFGE) and
      CsCl/ethidium bromide equilibrium centrifugation demonstrates that the NR-element
      represents circular DNA. Whereas it has been found in all field isolates of the
      parasites we analysed, it is not detectable in some laboratory strains notably
      the genome reference strain 927. The DNA sequence of this element is related to a
      29 bp repeat present in the subtelomeric region of VSG-bearing chromosomes of T.
      brucei. It has been suggested that this subtelomeric region is part of a
      transition zone on chromosomes separating the relatively stable telomeric repeats
      from the recombinationaly active region downstream of VSG genes. Therefore, we
      discuss a functional connection between the occurrence of this circular DNA and
      subtelomeric recombination events in T. brucei.

PMID- 12519184
TI  - The requirement of the LC8 dynein light chain for nuclear migration and septum
      positioning is temperature dependent in Aspergillus nidulans.
AB  - In the filamentous fungus Aspergillus nidulans, the multisubunit motor complex
      cytoplasmic dynein plays essential roles in nuclear migration and septum
      positioning. The 8 kDa light chain, LC8, the smallest subunit, is conserved among
      eukaryotic organisms. Besides being a component in the dynein complex, LC8 also
      interacts with a wide spectrum of mammalian and viral proteins. To date, the
      function of this small polypeptide is not well understood. To address this issue,
      we have created a deletion mutation (DeltanudG) at the nudG locus encoding LC8 in
      A. nidulans. At 42 degrees C, the DeltanudG mutant forms minute colonies lacking
      asexual reproduction: this phenotype resembles the phenotype of the dynein heavy
      chain null mutant. The mutant nuclei largely clustered in the spore body after
      conidial germination, and the septum was often assembled distally toward the
      hyphal apex, whereas a control germling has its nuclei distributed along the
      hypha and the septum formed near the spore body. When the mutant was grown at 23
      degrees C, however, its colony resembled a control one, and so did the patterns
      of nuclear distribution and septum positioning. Elevation of the growth
      temperature gradually reduced colony size and abolished asexual sporulation.
      After a period of growth at 23 degrees C that allowed the nuclei to move out of
      the spore end, a temperature shift to 42 degrees C prevented newly divided nuclei
      from migrating apart, suggesting that LC8/NUDG was required for both initiating
      and maintaining dynein motor functions at elevated temperatures. A functional GFP
      NUDA fusion was used to test whether LC8/NUDG is required for DHC (dynein heavy
      chain)/NUDA localization. We found that at 23 degrees C GFP-NUDA localized to the
      hyphal apex and the septation site in DeltanudG cells as in control cells. Such
      localizations were absent at 42 degrees C in mutant cells, but not in control
      cells. We conclude that LC8 plays a role in DHC localization/function, and the
      requirement for such a role in A. nidulans cells is temperature dependent.

PMID- 12519185
TI  - Autophagy is induced during cell death by incompatibility and is essential for
      differentiation in the filamentous fungus Podospora anserina.
AB  - In filamentous fungi, a cell death reaction occurs when cells of unlike genotype
      fuse. This cell death reaction, known as incompatibility reaction, is genetically
      controlled by a set of loci termed het loci (for heterokaryon incompatibility
      loci). In Podospora anserina, genes induced during this cell death reaction (idi
      genes) have been identified. The idi-6/pspA gene encodes a serine protease that
      is the orthologue of the vacuolar protease B of Saccharomyces cerevisiae involved
      in autophagy. We report here that the PSPA protease participates in the
      degradative autophagic pathway in Podospora. We have identified the Podospora
      orthologue of the AUT7 gene of S. cerevisiae involved in the early steps of
      autophagy in yeast. This gene is induced during the development of the
      incompatibility reaction and was designated idi-7. We have used a GFP-IDI7 fusion
      protein as a cytological marker of the induction of autophagy. Relocalization of
      this fusion protein and detection of autophagic bodies inside the vacuoles during
      the development of the incompatibility reaction provide cytological evidence of
      induction of autophagy during this cell death reaction. Therefore, cell death by
      incompatibility in fungi appears to be related to type II programmed cell death
      in metazoans. In addition, we found that pspA and idi-7 null mutations confer
      differentiation defects such as the absence of female reproductive structures,
      indicating that autophagy is required for differentiation in Podospora.

PMID- 12519186
TI  - Control of the Salmonella ugd gene by three two-component regulatory systems.
AB  - The Salmonella ugd gene is required for the incorporation of 4-aminoarabinose in
      the lipopolysaccharide and resistance to the antibiotic polymyxin B.
      Transcription of the ugd gene is induced by Fe3+ via the PmrA-PmrB two-component
      system and by low Mg2+ in a process that requires the PhoP-PhoQ two-component
      system, the PhoP-activated PmrD protein and the PmrA-PmrB system. Here, we
      establish that mutation of the tolB gene promotes ugd transcription independently
      of both the PhoP-PhoQ and PmrA-PmrB systems. This activation is mediated by the
      RcsC-YojN-RcsB phosphorelay and the RcsA protein, suggesting a role for ugd in
      capsule synthesis. Binding sites for the RcsB, PmrA and PhoP proteins were
      identified in the ugd promoter. Although the PmrA-PmrB and RcsC-YojN-RcsB systems
      promoted ugd transcription independently of the PhoP-PhoQ system under different
      environmental conditions, ugd expression inside macrophages was strictly
      dependent on PhoP-PhoQ, suggesting that low Mg2+ is a cue for the intracellular
      environment.

PMID- 12519187
TI  - A conserved sequence at the C-terminus of MinD is required for binding to the
      membrane and targeting MinC to the septum.
AB  - MinD is a key component of an oscillatory system that spatially regulates cell
      division in Escherichia coli. It is a peripheral membrane ATPase that recruits
      MinC and oscillates between the two halves of the cell in a MinE dependent
      manner. In vitro MinD binds to phospholipid vesicles in an ATP-dependent manner
      and is released through MinE-stimulated ATP hydrolysis. In this study we examined
      the function of the conserved C-terminus of MinD. Short truncations of three and
      ten amino acids dramatically decreased the ability of MinD to localize to the
      membrane and spatially regulate division. These truncations bound MinC but were
      deficient in targeting MinC to the septum. In vitro they dimerized, but were
      deficient in binding to phospholipid vesicles and undergoing MinE stimulation. We
      suggest a model in which the ATP-dependent dimerization of MinD affects the
      conformation of the C-terminal region, a potential amphipathic helix, triggering
      membrane binding.

PMID- 12519188
TI  - Identification and characterization of a Cryptococcus neoformans ATP binding
      cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to
      fluconazole.
AB  - Resistance to fluconazole is a possible event during prolonged suppressive drug
      therapy for cryptococ-cal meningitis, the most frequently encountered life
      threatening manifestation of cryptococcosis. The knowledge of this resistance at
      the molecular level is important for management of cryptococcosis. In order to
      identify genes involved in azole resistance in Cryptococcus neoformans, a cDNA
      subtraction library technique was chosen as a strategy. First, a fluconazole
      resistant mutant BPY22.17 was obtained from a susceptible clinical isolate BPY22
      by in vitro exposure to the drug. Then, a subtractive hybridization procedure was
      used to compare gene expression between the obtained strains. We identified a
      cDNA overexpressed in the fluconazole-resistant strain BPY22.17 that was used as
      a probe to isolate the entire gene in a C. neoformans genomic library. Sequence
      analysis of this gene identified an ATP Binding Cassette (ABC) transporter
      encoding gene called C. neoformans AntiFungal Resistance 1 (CnAFR1). Disruption
      of CnAFR1 gene in the resistant isolate (BPY22.17) resulted in an enhanced
      susceptibility of the knock-out mutant cnafr1 against fluconazole, whereas
      reintroduction of the gene in cnafr1 resulted in restoration of the resistance
      phenotype, thus confirming that CnAFR1 is involved in fluconazole resistance of
      C. neoformans. Our findings therefore reveal that an active drug efflux mechanism
      can be involved in the development of azole resistance in this important human
      pathogen.

PMID- 12519189
TI  - Lithium and valproate decrease the membrane
      phosphatidylinositol/phosphatidylcholine ratio.
AB  - Lithium and valproate, two structurally different anti-bipolar drugs, cause
      decreased intracellular inositol in the yeast Saccharomyces cerevisiae and an in
      crease in expression of a structural (INO1) and a regulatory (INO2) gene for
      phospholipid synthesis that responds to inositol depletion (Vaden, D., Ding, D.,
      Peterson, B., and Greenberg, M.L., 2001, J Biol Chem 276: 15466-15471). We report
      here that both drugs decrease the relative rate of membrane phosphatidylinositol
      synthesis and, to a lesser but still significant degree, the steady state
      relative phosphatidylinositol composition. In addition, both drugs increase the
      rate of phosphatidylcholine (PC) synthesis. Finally, valproate, but not lithium,
      increases expression of phosphatidylcholine pathway genes CHO1 and OPI3. The
      overall effect on membrane phospholipid composition is a reduction in the
      phosphatidylinositol/phosphatidylcholine ratio by both drugs. Because maintenance
      of the appropriate phosphatidylinositol/phosphatidylcholine ratio is required for
      secretory vesicle formation, a decrease in this ratio may have far-reaching
      implications for understanding the therapeutic mechanisms of action of these
      drugs.

PMID- 12519190
TI  - Proteome analysis of Escherichia coli K-12 by two-dimensional native-state
      chromatography and MALDI-MS.
AB  - To identify proteins expressed in Escherichia coli K-12 MG1655 during exponential
      growth in defined medium, we separated soluble proteins of E. coli over two
      dimensions of native-state high-performance liquid chromatography, and examined
      the components of the protein mixtures in each of 380 fractions by peptide mass
      fingerprinting. To date, we have identified the products of 310 genes covering a
      wide range of cellular functions. Validation of protein assignments was made by
      comparing the assignments of proteins to specific first-dimension fractions to
      proteins visualized by two-dimensional gel electrophoresis. Co-fractionation of
      proteins suggests the possible identities of components of multiprotein
      complexes. This approach yields high-throughput gel-independent identification of
      proteins. It can also be used to assign identities to spots visualized by two
      dimensional gels, and should be useful to evaluate differences in expressed
      proteome content and protein complexes among strains or between different
      physiological states.

PMID- 12519191
TI  - DNA gyrase requirements distinguish the alternate pathways of Mu transposition.
AB  - The MuA transposase mediates transposition of bacteriophage Mu through two
      distinct mechanisms. The first integration event following infection occurs
      through a non-replicative mechanism. In contrast, during lytic growth, multiple
      rounds of replicative transposition amplify the phage genome. We have examined
      the influence of gyrase and DNA supercoiling on these two transposition pathways
      using both a gyrase-inhibiting drug and several distinct gyrase mutants. These
      experiments reveal that gyrase activity is not essential for integration; both
      lysogens and recombination intermediates are detected when gyrase is inhibited
      during Mu infection. In contrast, gyrase inhibition causes severe defects in
      replicative transposition. In two of the mutants, as well as in drug-treated
      cells, replicative transposition is almost completely blocked. Experiments
      probing for formation of MuA-DNA complexes in vivo reveal that this block occurs
      very early, during assembly of the transposase complex required for the catalytic
      steps of recombination. The findings establish that DNA structure-based signals
      are used differently for integrative and replicative transposition. We propose
      that transposase assembly, the committed step for recombination, has evolved to
      depend on different DNA /architectural signals to control the reaction outcome
      during these two distinct phases of the phage life cycle.

PMID- 12519192
TI  - Molecular characterization, function and regulation of ammonium transporters
      (Amt) and ammonium-metabolizing enzymes (GS, NADP-GDH) in the ectomycorrhizal
      fungus Hebeloma cylindrosporum.
AB  - External hyphae, which play a key role in nitrogen nutrition of trees, are
      considered as the absorbing structures of the ectomycorrhizal symbiosis. Here, we
      have cloned and characterized Hebeloma cylindrosporum AMT1, GLNA and GDHA genes,
      which encode a third ammonium transporter, a glutamine synthetase and an NADP
      dependent glutamate dehydrogenase respectively. Amt1 can fully restore the
      pseudohyphal growth defect of a Saccharomyces cerevisiae mep2 mutant, and this is
      the first evidence that a heterologous member of the Mep/Amt family complements
      this dimorphic change defect. Dixon plots of the inhibition of methylamine uptake
      by ammonium indicate that Amt1 has a much higher affinity than the two previously
      characterized members (Amt2 and Amt3) of the Amt/Mep family in H. cylindrosporum.
      We also identified the intracellular nitrogen pool(s) responsible for the
      modulation of expression of AMT1, AMT2, AMT3, GDHA and GLNA. In response to
      exogenously supplied ammonium or glutamine, AMT1, AMT2 and GDHA were
      downregulated and, therefore, these genes are subjected to nitrogen repression in
      H. cylindrosporum. Exogenously supplied nitrate failed to induce a downregulation
      of the five mRNAs after transfer of mycelia from a N-starved condition. Our
      results demonstrate that glutamine is the main effector for AMT1 and AMT2
      repression, whereas GDHA repression is controlled by intracellular ammonium,
      independently of the intracellular glutamine or glutamate concentration. Ammonium
      transport activity may be controlled by intracellular NH4+. AMT3 and GLNA are
      highly expressed but not highly regulated. A model for ammonium assimilation in
      H. cylindrosporum is presented.

PMID- 12519193
TI  - Divergence and transcriptional analysis of the division cell wall (dcw) gene
      cluster in Neisseria spp.
AB  - Three of the 18 open reading frames in the division and cell wall synthesis
      cluster of the pathogenic Neisseria spp. are not present in the clusters of other
      bacterial species. The region containing two of these, dcaB and dcaC, displays
      interstrain and interspecies variability uncharacteristic of such clusters. 3' of
      dcaB is a Correia repeat enclosed element (CREE), which is only present in some
      strains. It has been suggested that this CREE is a transcriptional terminator,
      although we demonstrate otherwise. A gearbox-like promoter within this CREE is
      active in Escherichia coli but not in Neisseria meningitidis. There is an active
      promoter 5' of dcaC, although its sequence is not conserved. The presence of
      similarly located promoters has not been demonstrated in other species. In
      Neisseria lactamica, this promoter involves another dcw-associated CREE, the
      first demonstration of active promoter generation at the 5' end of this common
      intergenic, apparently mobile, element. Upstream of this promoter is an inverted
      pair of neisserial uptake signal sequences, which are commonly considered to be
      transcriptional terminators. It has been proposed to terminate transcription in
      this location, although we have demonstrated transcript extending through this
      uptake signal sequence. dcaC contains a 108 bp tandem repeat, which is present in
      different copy numbers in the neisserial strains examined. This investigation
      reveals extensive sequence variation, disputes the presence of transcriptional
      terminators and identifies active internal promoters in this normally highly
      conserved cluster of essential genes, and addresses the transcriptional activity
      of two common neisserial intergenic components.

PMID- 12519194
TI  - A novel apoptosis-inducing protein from Helicobacter pylori.
AB  - Helicobacter pylori infection induces apoptosis in gastric epithelial cells.
      Here, we report a novel apoptosis-inducing protein that functions as a leading
      factor in H. pylori-mediated apoptosis induction. We purified the protein from H.
      pylori by separating fractions that showed apoptosis-inducing activity. This
      protein induced apoptosis of AGS cells in a dose-dependent manner. The purified
      protein consisted of two protein fragments with molecular masses of about 40 and
      22 kDa, which combined to constitute a single complex in their natural form. N
      terminal sequencing indicated that both these protein fragments were encoded by
      the HP1118 gene. The purified protein exhibited gamma-glutamyl transpeptidase
      activity, the inhibition of which by 6-diazo-5-oxo-l-norleucine resulted in a
      complete loss of apoptosis-inducing activity. To the best of our knowledge, the
      apoptosis-inducing function is a newly identified physiological role for
      bacterial gamma-glutamyl transpeptidase. The apoptosis-inducing activity of the
      isogenic mutant gamma-glutamyl transpeptidase-deficient strain was significantly
      lower compared with that of the parent strain, demonstrating that gamma-glutamyl
      transpeptidase plays a significant role in H. pylori-mediated apoptosis. Our
      findings provide new insights into H. pylori pathogenicity and reveal a novel
      aspect of the bacterial gamma-glutamyl transpeptidase function.

PMID- 12519195
TI  - Glycolipid depletion in antimicrobial therapy.
AB  - Mucosal pathogens target sites of infection through specific adherence to host
      glycoconjugate receptors. As a consequence, depletion of such receptors from the
      cell surface may be expected to inhibit attachment, impair bacterial colonization
      and reduce the activation of mucosal inflammation. We have used the glucose
      analogue and glycosphingolipid (GSL) biosynthesis inhibitor N
      butyldeoxynojirimycin (NB-DNJ) to deplete human uroepithelial cells and the
      murine urinary tract mucosa of receptors for P-fimbriated Escherichia coli. NB
      DNJ blocks the ceramide-specific glucosyltransferase, which catalyses the
      formation of glucosyl ceramide (GlcCer), the precursor for GSLs. The inhibitor
      was shown to decrease the GSL content in a dose-dependent way, and depletion
      markedly inhibited P-fimbriated bacterial attachment in vitro. NB-DNJ-fed C3H/HeN
      mice were depleted of GSLs in vivo and showed reduced susceptibility to
      experimental urinary tract infection with P-fimbriated E. coli. The mucosal
      inflammatory response was impaired, as shown by reduced chemokine secretion and
      lower neutrophil recruitment, and the bacteria colonized the urinary tract less
      efficiently than in normal mice. These results confirmed the role of P fimbriae
      mediated adherence for colonization and inflammation and point to an interesting
      alternative to antibiotic treatment for urinary tract infection.

PMID- 12519196
TI  - Molecular analysis of fusidic acid resistance in Staphylococcus aureus.
AB  - Fusidic acid is a potent antibiotic against severe Gram-positive infections that
      interferes with the function of elongation factor G (EF-G), thereby leading to
      the inhibition of bacterial protein synthesis. In this study, we demonstrate that
      fusidic acid resistance in Staphylococcus aureus results from point mutations
      within the chromosomal fusA gene encoding EF-G. Sequence analysis of fusA
      revealed mutational changes that cause amino acid substitutions in 10 fusidic
      acid-resistant clinical S. aureus strains as well as in 10 fusidic acid-resistant
      S. aureus mutants isolated under fusidic acid selective pressure in vitro.
      Fourteen different amino acid exchanges were identified that were restricted to
      13 amino acid residues within EF-G. To confirm the importance of observed amino
      acid exchanges in EF-G for the generation of fusidic acid resistance in S.
      aureus, three mutant fusA alleles encoding EF-G derivatives with the exchanges
      P406L, H457Y and L461K were constructed by site-directed mutagenesis. In each
      case, introduction of the mutant fusA alleles on plasmids into the fusidic acid
      susceptible S. aureus strain RN4220 caused a fusidic acid-resistant phenotype.
      The elevated minimal inhibitory concentrations of fusidic acid determined for the
      recombinant bacteria were analogous to those observed for the fusidic acid
      resistant clinical S. aureus isolates and the in vitro mutants containing the
      same chromosomal mutations. Thus, the data presented provide evidence for the
      crucial importance of individual amino acid exchanges within EF-G for the
      generation of fusidic acid resistance in S. aureus.

PMID- 12519197
TI  - Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and
      cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the
      myxobacterium Stigmatella aurantiaca.
AB  - Steroids, such as cholesterol, are synthesized in almost all eukaryotic cells,
      which use these triterpenoid lipids to control the fluidity and flexibility of
      their cell membranes. Bacteria rarely synthesize such tetracyclic compounds but
      frequently replace them with a different class of triterpenoids, the pentacyclic
      hopanoids. The intriguing mechanisms involved in triterpene biosynthesis have
      attracted much attention, resulting in extensive studies of squalene-hopene
      cyclase in bacteria and (S)-2,3-oxidosqualene cyclases in eukarya. Nevertheless,
      almost nothing is known about steroid biosynthesis in bacteria. Only three
      steroid-synthesizing bacterial species have been identified before this study.
      Here, we report on a variety of sterol-producing myxobacteria. Stigmatella
      aurantiaca is shown to produce cycloartenol, the well-known first cyclization
      product of steroid biosynthesis in plants and algae. Additionally, we describe
      the cloning of the first bacterial steroid biosynthesis gene, cas, encoding the
      cycloartenol synthase (Cas) of S. aurantiaca. Mutants of cas generated via site
      directed mutagenesis do not produce the compound. They show neither growth
      retardation in comparison with wild type nor any increase in ethanol sensitivity.
      The protein encoded by cas is most similar to the Cas proteins from several plant
      species, indicating a close evolutionary relationship between myxobacterial and
      eukaryotic steroid biosynthesis.

PMID- 12519198
TI  - Inducible bacteriocin production in Lactobacillus is regulated by differential
      expression of the pln operons and by two antagonizing response regulators, the
      activity of which is enhanced upon phosphorylation.
AB  - Expression of the five (pln) operons involved in the bacteriocin production of
      Lactobacillus plantarum C11 is regulated by a so-called pheromone-based signal
      transducing network, in which the peptide pheromone (PlnA) induces bacteriocin
      production through the action of a histidine protein kinase (PlnB) and two
      antagonizing response regulators (PlnC as an activator and PlnD as a negative
      regulator). All pln-regulated promoters contain a conserved pair of direct
      repeats that serve as binding sites for PlnC and PlnD. In the present work, we
      show that the five PlnA-responsive operons are differentially expressed with
      regard to both timing and strength, and that the pheromone triggers a strong
      autoactivating loop of the regulatory unit (plnABCD) during an early stage of
      induction that gradually leads to enhanced activation of the other operons. The
      transport operon (plnGHSTUV), which is involved in the secretion of the pheromone
      and bacteriocins, is also expressed relatively early upon induction, but is
      quickly turned off soon after peak expression. Further investigation of the
      various promoters revealed that, although subtle differences within the promoter
      regions could account for the observed differential regulation, the presence of a
      downstream promoter-proximal sequence in one promoter was found to cause delayed
      peak activity. How phosphorylation regulates the activity of the pln response
      regulators was also accessed by direct mutagenesis at their phosphorylation
      sites. It was found that the two response regulators exert activity at two
      different levels: a low level when they are not phosphorylated and an elevated
      level when they are phosphorylated. The present data demonstrate that bacteriocin
      production in L. plantarum C11 is a highly regulated process, in which different
      regulatory mechanisms are applied to fine tune the timing and strength of
      expression of the five pln operons.

PMID- 12519199
TI  - The product of the UTH1 gene, required for Bax-induced cell death in yeast, is
      involved in the response to rapamycin.
AB  - A yeast mutant was isolated that was resistant to Bax-induced cell death. It
      supports a mutation leading to decreased amounts of the protein Uth1p. A strain
      in which the UTH1 gene is disrupted also exhibits resistance to Bax expression.
      The absence of Uth1p does not change the mitochondrial localization of Bax, its
      insertion in the mitochondrial outer membrane or its cytochrome c-releasing
      activity. On the other hand, the absence of Uth1p does prevent the appearance of
      other hallmarks related to Bax expression in yeast, such as oxidation of
      mitochondrial lipid, production of reactive oxygen species and maintenance of
      plasma membrane properties after ethanol stress. The absence of Uth1p was also
      found to induce resistance to rapamycin, a specific inducer of autophagy. This
      resistance only appears when cells are grown under respiratory conditions, but
      not under fermentative conditions, suggesting that Uth1p acts in an autophagic
      pathway involving mitochondria, in accordance with its main localization in the
      outer mitochondrial membrane. Taken together, these data show that Bax is able to
      activate a death pathway related to autophagy in yeast, which also exhibits
      typical hallmarks of apoptosis, revealing a possible dual function of Bax in both
      types of death. This hypothesis is discussed in the light of observations
      suggesting a co-regulation of apoptosis and autophagy in mammalian cells.

PMID- 12519200
TI  - Rga5p is a specific Rho1p GTPase-activating protein that regulates cell integrity
      in Schizosaccharomyces pombe.
AB  - Schizosaccharomyces pombe Rho1p regulates (1,3)beta-d-glucan synthesis and is
      required for cell integrity maintenance and actin cytoskeleton organization, but
      nothing is known about the regulation of this protein. At least nine different S.
      pombe genes code for proteins predicted to act as Rho GTPase-activating proteins
      (GAPs). The results shown in this paper demonstrate that the protein encoded by
      the gene named rga5+ is a GAP specific for Rho1p. rga5+ overexpression is lethal
      and causes morphological alterations similar to those reported for Rho1p
      inactivation. rga5+ deletion is not lethal and causes a mild general increase in
      cell wall biosynthesis and morphological alterations when cells are grown at 37
      degrees C. Upon mild overexpression, Rga5p localizes to growth areas and
      possesses both in vivo and in vitro GAP activity specific for Rho1p.
      Overexpression of rho1+ in rga5Delta cells is lethal, with a morphological
      phenotype resembling that of the overexpression of the constitutively active
      allele rho1G15V. In addition (1,3)beta-d-glucan synthase activity, regulated by
      Rho1p, is increased in rga5Delta cells and decreased in rga5-overexpressing
      cells. Moreover, the increase in (1,3)beta-d-glucan synthase activity caused by
      rho1+ overexpression is considerably higher in rga5Delta than in wild-type cells.
      Genetic interactions suggest that Rga5p is also important for the regulation of
      the other known Rho1p effectors, Pck1p and Pck2p.

PMID- 12519201
TI  - Putrescine or a combination of methionine and arginine restores virulence gene
      expression in a tRNA modification-deficient mutant of Shigella flexneri: a
      possible role in adaptation of virulence.
AB  - The wild-type strain YSH6000 of Shigella flexneri growing in minimal medium
      contains the modified nucleoside epoxy-Q (oQ) in a subset of tRNAs. This
      nucleoside is lacking in tRNA from a tgt mutant of this bacterium. When these
      bacteria are growing in minimal medium, the expression of virulence genes is 10
      fold lower in the tgt mutant than in the wild type, although only a twofold
      reduction in the expression of these virulence factors is observed in broth. Such
      a strong media-dependant expression of virulence genes was not observed in the
      wild type. Accordingly, the level of the positive regulator of virulence, VirF,
      is much lower in the mutant than in the wild type. However, the transcription of
      the virF gene in minimal medium is the same in the wild type and in the tgt
      mutant. As the undermodification of tRNA is not affected by the quality of the
      growth medium, we conclude that such an environmental change in growth conditions
      partly restores virulence gene expression by counteracting poor translation of
      the virF mRNA mediated by an oQ-deficient tRNA. Virulence gene expression is
      partly restored in the tgt mutant by the addition of a mixture of arginine and
      methionine. Addition of the polyamine putrescine, synthesis of which is
      metabolically related to that of arginine and methionine, has a comparable
      stimulatory effect on virulence gene expression. These results not only suggest a
      role for amino acids and polyamines in the environmental regulation of virulence
      gene expression in S. flexneri, but also demonstrate a strong and specific
      involvement of tRNA modifications, and especially oQ, in the adaptation of
      virulence gene expression to the nutritional quality of the growth medium.

PMID- 12519202
TI  - Linkage disequilibrium between minisatellite loci supports clonal evolution of
      Mycobacterium tuberculosis in a high tuberculosis incidence area.
AB  - Deciphering the structure of pathogen populations is instrumental for the
      understanding of the epidemiology and history of infectious diseases and for
      their control. Although Mycobacterium tuberculosis is the most widespread
      infectious agent in humans, its actual population structure has remained
      hypothetical until now because: (i) its structural genes are poorly polymorphic;
      (ii) adequate samples and appropriate statistics for population genetic analysis
      have not been considered. To investigate this structure, we analysed the
      statistical associations (linkage disequilibrium) between 12 independent M.
      tuberculosis minisatellite-like loci by high-throughput genotyping within a model
      population of 209 isolates representative of the genetic diversity in an area
      with a very high incidence of tuberculosis. These loci contain variable number
      tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed
      repetitive units (MIRUs). Highly significant linkage disequilibrium was detected
      among the MIRU-VNTR loci in this model. This linkage disequilibrium was also
      evident when the MIRU-VNTR types were compared with the IS6110 restriction
      fragment length polymorphism types. These results support a predominant clonal
      evolution of M. tuberculosis.

PMID- 12519203
TI  - Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in
      the lateral wall and at mid-cell in comparison with the old cell pole.
AB  - The localization of penicillin-binding protein 2 (PBP2) in Escherichia coli has
      been studied using a functional green fluorescent protein (GFP)-PBP2 fusion
      protein. PBP2 localized in the bacterial envelope in a spot-like pattern and also
      at mid-cell during cell division. PBP2 disappeared from mid-cell just before
      separation of the two daughter cells. It localized with a preference for the
      cylindrical part of the bacterium in comparison with the old cell poles, which
      are known to be inert with respect to peptidoglycan synthesis. In contrast to
      subunits of the divisome, PBP2 failed to localize at mid-cell when PBP3 was
      inhibited by the specific antibiotic aztreonam. Therefore, despite its dependency
      on active PBP3 for localization at mid-cell, it seems not to be an integral part
      of the divisome. Cells grown for approximately half a mass doubling time in the
      presence of the PBP2 inhibitor mecillinam synthesized nascent cell poles with an
      increased diameter, indicating that PBP2 is required for the maintenance of the
      correct diameter of the new cell pole.

PMID- 12519204
TI  - Induction of apoptosis in macrophages by Pseudomonas aeruginosa azurin: tumour
      suppressor protein p53 and reactive oxygen species, but not redox activity, as
      critical elements in cytotoxicity.
AB  - Azurin is a copper-containing protein involved in electron transfer during
      denitrification. We reported recently that purified azurin demonstrates
      cytotoxicity to macrophages by forming a complex with the tumour-suppressor
      protein p53, thereby stabilizing it and enhancing its function as an inducer of
      proapoptotic activity (Yamada, T., Goto, M., Punj, V., Zaborina, O., Kimbara, K.,
      Das Gupta, T. K., and Chakrabarty, A. M. 2002, Infect Immun70: 7054-7062). It is,
      however, not known whether the oxidoreductase (redox) activity of azurin or the
      involvement of copper is important for its cytotoxicity. We have isolated apo
      azurin devoid of copper and site-directed mutants that are redox negative because
      of either replacement of a cysteine residue (Cys-112) involved in co-ordination
      with copper or mutational replacement of two methionine residues (Met-44 and Met
      64) that are present in the hydrophobic patch of azurin and allow interaction of
      azurin with its redox partner cytochrome c551. We demonstrate that, although the
      wild type (wt) and the Cys-112 Asp mutant azurin can form complexes with the
      tumour-suppressor protein p53 and generate high levels of reactive oxygen species
      (ROS), the redox-negative Met-44LysMet-64Glu mutant azurin is defective in
      complex formation with p53, generates low levels of ROS and lacks appreciable
      cytotoxicity towards macrophages. Thus, complex formation with p53 and ROS
      generation, rather than azurin redox activity, are important in the cytotoxic
      action of azurin towards macrophages.

PMID- 12519205
TI  - A novel regulatory gene for light-induced carotenoid synthesis in the bacterium
      Myxococcus xanthus.
AB  - Myxococcus xanthus cells respond to blue light by producing carotenoids. Light
      triggers a network of regulatory actions that lead to the transcriptional
      activation of the carotenoid genes. By screening the colour phenotype of a
      collection of Tn5-lac insertion mutants, we have isolated a new mutant devoid of
      carotenoid synthesis. We map the transposon insertion, which co-segregates with
      the mutant phenotype, to a previously unknown gene designated here as carF. An in
      frame deletion within carF causes the same phenotype as the Tn5-lac insertion.
      The carF deletion prevents the activation of the normally light-inducible genes,
      without affecting the expression of any of the regulatory genes known to be
      expressed in a light-independent manner. Until now, the switch that sets off the
      regulatory cascade had been identified with light-driven inactivation of protein
      CarR, an antisigma factor. The exact mechanism of this inactivation has remained
      elusive. We show by epistatic analysis that the carF gene product participates in
      the light-dependent inactivation of CarR. The predicted CarF amino acid sequence
      reveals no known prokaryotic homologues. On the other hand, CarF is remarkably
      similar to Kua, a family of proteins of unknown function that is widely
      distributed among eukaryotes.

PMID- 12519206
TI  - DNA binding properties of the HrmR protein of Nostoc punctiforme responsible for
      transcriptional regulation of genes involved in the differentiation of
      hormogonia.
AB  - Nostoc punctiforme is an example of a filamentous cyanobacterium that is capable
      of differentiating non-growing cells that constitute gliding filaments termed
      hormogonia. These gliding filaments serve in short distance dispersal and as
      infective units in establishing a symbiosis with plants, such as the bryophyte
      Anthoceros punctatus. Mutants of N. punctiforme exist which show elevated levels
      of initial infection of A. punctatus as a consequence of repeated cycles of
      hormogonium differentiation. Such mutations occur within the hrmA and hrmU genes.
      Further characterization of the hrm locus revealed several genes with an
      organizational and predicted protein sequence similarity to genes of
      heterotrophic bacteria that are involved in hexuronic acid metabolism. Genes in
      the N. punctiforme locus are transcribed in response to the presence of a plant
      extract containing hormogonium-repressing factors. A predicted transcriptional
      repressor encoded in the locus, HrmR, was shown herein to be a specific DNA
      binding protein that regulates the transcription of its own gene and that of
      hrmE, a nearby gene. The ability of HrmR to bind DNA was abolished upon addition
      of either galacturonate or lysate from specifically induced N. punctiforme cells,
      implying that the in vivo HrmR binding activity is modulated via an internal
      compound, most likely a sugar molecule.

PMID- 12519207
TI  - Thinking and decision making, bacterial style: Bacterial Neural Networks,
      Obernai, France, 7th-12th June 2002.
AB  - Bacteria exhibit a bewildering range of behavioural responses and permutations of
      metabolic pathways for maximum exploitation of their environment. These are based
      on sensory perception of external and internal signals through batteries of
      surface and cytoplasmic receptors, evaluation of complex information flows and
      rapid decision making. Appreciation of the diversity of bacterial behaviour and
      adaptation capacities requires the study of a broad range of organisms and at
      this meeting we sampled more than 30 species with new findings which included the
      nature of gaseous receptors, advances in chemotaxis, subversion of host defences
      by pathogens, adaptation to high salt, community life and its obvious benefits,
      cell to cell communications and even the nature of bacterial circadian rhythms.
      With around 80 bacterial genomes now completed, and many more almost there, it
      was appropriate to complete the meeting with an introduction to Systems Biology
      and prospects for simulating the virtual cell. The versatility and seemingly
      'intelligent' behaviour of bacteria will continue to fascinate, and this meeting
      on Bacterial Neural Networks fully reflected the excitement of this field.

PMID- 12519208
TI  - Phosphate availability regulates biosynthesis of two antibiotics, prodigiosin and
      carbapenem, in Serratia via both quorum-sensing-dependent and -independent
      pathways.
AB  - Serratia sp. ATCC 39006 produces two secondary metabolite antibiotics, 1-carbapen
      2-em-3-carboxylic acid (Car) and the red pigment, prodigiosin (Pig). We have
      previously reported that production of Pig and Car is controlled by N-acyl
      homoserine lactone (N-AHL) quorum sensing, with synthesis of N-AHLs directed by
      the LuxI homologue SmaI, and is also regulated by Rap, a member of the SlyA
      family. We now describe further characterization of the SmaI quorum-sensing
      system and its connection with other regulatory mechanisms. We show that the
      genes responsible for biosynthesis of Pig, pigA-O, are transcribed as a single
      polycistronic message in an N-AHL-dependent manner. The smaR gene, transcribed
      convergently with smaI and predicted to encode the LuxR homologue partner of
      SmaI, was shown to possess a negative regulatory function, which is uncommon
      among the LuxR-type transcriptional regulators. SmaR represses transcription of
      both the pig and car gene clusters in the absence of N-AHLs. Specifically, we
      show that SmaIR exerts its effect on car gene expression via transcriptional
      control of carR, encoding a pheromone-independent LuxR homologue. Transcriptional
      activation of the pig and car gene clusters also requires a functional Rap
      protein, but Rap dependency can be bypassed by secondary mutations. Transduction
      of these suppressor mutations into wild-type backgrounds confers a hyper-Pig
      phenotype. Multiple mutations cluster in a region upstream of the pigA gene,
      suggesting this region may represent a repressor target site. Two mutations
      mapped to genes encoding pstS and pstA homologues, which are parts of a high
      affinity phosphate transport system (Pst) in Escherichia coli. Disruption of pstS
      mimicked phosphate limitation and caused concomitant hyper-production of Pig and
      Car, which was mediated, in part, through increased transcription of the smaI
      gene. The Pst and SmaIR systems define distinct, yet overlapping, regulatory
      circuits which form part of a complex regulatory network controlling the
      production of secondary metabolites in Serratia ATCC 39006.

PMID- 12519209
TI  - Effects of intestinal survival surgery on systemic and mucosal immune responses
      in SIV-infected rhesus macaques.
AB  - Evaluation of cellular immunity in the intestinal lamina propria of rhesus
      macaques has been used previously to assess protective immunity against mucosal
      simian immunodeficiency virus (SIV) challenges. As this technique requires
      survival surgery to obtain jejunal tissue, effects of surgical stress on the
      immune system were investigated. SIV-specific immune responses, including IgG and
      IgA binding antibodies in sera and mucosal secretions, IgG and IgA secreting
      cells in peripheral blood, IgG neutralizing antibodies, T-cell proliferative
      responses, and interferon-gamma secretion by peripheral blood mononuclear cells,
      were evaluated pre- and post-surgery in macaques immunized with adenovirus-SIV
      recombinant vaccines and SIV envelope protein and in SIV-infected macaques. No
      differences in these immune parameters were observed in SIV-naive, immunized
      macaques or healthy SIV-infected macaques with regard to surgery. A dramatic
      increase in total IgA antibody level following surgery in the rectal secretions
      of one SIV-infected macaque that was rapidly progressing to AIDS and failed to
      recover from surgery was attributed to an abscess that developed at the
      intestinal site. To date, nearly 30 other macaques have undergone the intestinal
      survival surgery, some on more than one occasion, without experiencing any
      clinical difficulty. Overall, our results suggest that in healthy macaques,
      intestinal resection survival surgery can be conducted safely. Further, the
      method can be used to reliably sample the intestinal mucosa without major or
      persistent impact on humoral or cellular immune responses.

PMID- 12519210
TI  - Immune responses in baboons vaccinated with HIV-2 genetic expression libraries.
AB  - Immunization using genetic expression libraries may be an improvement over
      conventional DNA immunization using a single gene because more epitopes are
      simultaneously presented to the immune system. In this study, we evaluated the
      effectiveness of an HIV-2 vaccine made from a genomic expression library in
      baboons. We found that HIV-2 expression library immunization induced HIV-2
      specific memory responses but low levels of CD8+ cell anti-viral responses and
      neutralizing antibodies. After intravenous virus challenge using a homologous
      pathogenic variant, HIV-2UC2/9429, viral loads were similar in the HIV-2
      immunized and control baboons. We conclude that although immunization using HIV-2
      expression libraries induces immune responses, this approach does not provide
      protection in baboons against intravenous challenge with HIV-2.

PMID- 12519212
TI  - Baseline and stress levels of cortisol in conscious and unrestrained Japanese
      macaques (Macaca fuscata).
AB  - A vest and tethering system was applied to Japanese macaques (Macaca fuscata) to
      collect blood samples under less stressful conditions. The level of plasma
      cortisol was assayed to assess the amount of stress. The pattern of plasma
      cortisol fluctuation during 24 hours was consistent under non-stress conditions.
      The plasma cortisol level was increased significantly by encounter and
      venipuncture. The increase was especially noteworthy when the experimental
      macaques encountered a large adult male, reflecting the strong stress on
      macaques. As venipuncture is a common medical procedure, and the encounter
      between macaques who have never met before occurs frequently, this vest and
      tethering system is useful for the assessment of the amount of stress in the
      daily care of macaques in a laboratory.

PMID- 12519211
TI  - Endometrial function in vervet monkeys (Cercopithecus aethiops): morphology,
      beta3 integrin and insulin-like growth factor binding protein-1 expression during
      the menstrual cycle and pregnancy in the normal and disrupted endometrium.
AB  - The expression of endometrial beta3 integrin and insulin-like growth factor
      binding protein-1 (IGFBP-1) was studied in cycling and pregnant vervet monkeys.
      There were clear changes of beta3 integrin expression during the menstrual cycle,
      with the strongest immunostaining observed on day 26. Moderate to strong
      expression was observed during pregnancy. The expression of IGFBP-1 during the
      menstrual cycle was weak but upregulated during pregnancy with moderate to strong
      staining. The administration of a single dose of onapristone at 10 mg/kg on days
      17, 21 and 22 of the menstrual cycle, followed by a biopsy on days 22, 22 and 26,
      respectively, and during pregnancy (34-44 days menstrual age) 24 h before the
      biopsy, disrupted and desynchronized the endometrium. However, no effect on beta3
      integrin expression could be observed and staining reflected the untreated
      patterns. The same applied to IGFBP-1 except that during pregnancy the expression
      of this protein was reduced or abolished. The results suggest that beta3 integrin
      is associated with endometrial receptivity in vervet monkeys and that IGFBP-1
      plays an important role during pregnancy in this species. The administration of
      onapristone appeared to only influence IGFBP-1 expression. To our knowledge, this
      is the first time that these endometrial proteins have been investigated in
      vervet monkeys. This study should therefore contribute to improving our
      understanding of the reproductive function of this species.

PMID- 12519213
TI  - Spontaneous rat bite fever in non-human primates: a review of two cases.
AB  - Rat bite fever is a worldwide zoonotic, non-reportable disease. This entity
      encompasses similar, yet distinct, disease syndromes caused by Streptobacillus
      moniliformis or Spirillum minus. Naturally occurring rat bite fever has not been
      previously described in non-human primates. This report describes two cases of
      non-human primate rat bite fever caused by S. moniliformis; a rhesus macaque
      (Macaca mullata) with valvular endocarditis, and a titi monkey (Callicebus sp.)
      with septic arthritis. Potential sources of infection included direct contact,
      and ingestion of surface water or feed contaminated with rodent feces.

PMID- 12519214
TI  - Congenitally caused fused labia in the common marmoset (Callithrix jacchus).
AB  - In this paper, the occurrence of an external genital abnormality in female
      marmoset monkeys (fused labia) is discussed. This malformation was detected, for
      the first time, in a group of animals at the German Primate Center (GPC),
      Goettingen. The malformed vulva was completely sealed except for an opening of
      1.5-2.5 mm around the urethra sufficient for urination. Because of this defect
      the animals were not able to copulate. As a consequence, the affected females
      were functionally infertile although they had a normal genital tract and a
      regular cycle. This vulvar abnormality was found in 12 females, offspring of 10
      pairs in which either one or both came to the German Primate Center from two
      genetically related colonies in Munich, Germany, and one colony in Basel,
      Switzerland. The abnormality appeared to be recessive and inheritable from either
      parent. In pairs in which both animals were from one of the mentioned colonies,
      45% of the female offspring were affected. In pairs where only one partner came
      from these colonies, 26% of female offspring had the malformation. These results
      indicate that avoidance of inbreeding, which is frequently performed in primate
      colonies, may reduce, but not eliminate the expression of abnormalities of
      genetic origin. Therefore selective breeding is required, and, in colonies where
      these recessive mutations are widespread, the development of genetic screening
      tests would be advantageous.

PMID- 12519216
TI  - Parathyroid hormone-related peptide: A jack of all trades that masters gastric
      responses to stress.

PMID- 12519217
TI  - Oval cell-mediated liver regeneration: Role of cytokines and growth factors.
AB  - In experimental models, which induce liver damage and simultaneously block
      hepatocyte proliferation, the recruitment of a hepatic progenitor cell population
      comprised of oval cells is invariably observed. There is a substantial body of
      evidence to suggest that oval cells are involved in liver regeneration, as they
      differentiate into hepatocytes and biliary cells. Recently, bone marrow cells
      were shown to be a source of a stem cells with the capacity to repopulate the
      liver. Presently, the relationship between bone marrow cells and oval cells is
      unclear. Investigations will be greatly assisted by the availability of in vitro
      models based on a knowledge of cytokines that affect oval cells. While the
      cytokines, which regulate the different hematopoietic lineages, are well
      characterized, there is relatively little information regarding those that
      influence oval cells. This review outlines recent developments in the field of
      oval cell research and focuses on cytokines and growth factors that have been
      implicated in regulating oval cell proliferation and differentiation.

PMID- 12519218
TI  - Low Helicobacter pylori eradication rates with 4- and 7-day regimens in an
      Iranian population.
AB  - BACKGROUND: In Iran, there is insufficient information on the efficacy of
      Helicobacter pylori eradication regimens shorter than 10 days. This study aims at
      assessing the efficacy of 4- and 7-day H. pylori eradication regimens in a high
      incidence area of gastric cancer in Iran. METHODS: Subjects with an endoscopic
      diagnosis of gastritis, positive urease test, and a histological diagnosis of
      chronic gastritis were enrolled. Patients were randomly assigned to one of three
      groups: AOC7 (1000 mg amoxicillin, 20 mg omeprazole, and 500 mg clarithromycin
      twice daily for 7 days), FOT4 (200 mg furazolidone, 20 mg omeprazole, and 500 mg
      tetracycline twice daily for 4 days) and FOT7 (the same treatment as the FOT4
      group but for 7 days). Sensitivity to these antibiotics was determined in all
      isolates recovered from culture. The efficacy of eradication was assessed 8 weeks
      after the end-of-treatment by the 14C-urea breath test. RESULTS: One hundred and
      twenty-eight patients were enrolled in the study. Culture was positive for 84
      patients and none of these were resistant to amoxicillin, tetracycline or
      furazolidone, 1.2% were resistant to clarithromycin and 32.1% to metronidazole.
      Forty-five, 41 and 42 patients were randomly allocated to the AOC7, FOT4, and
      FOT7 groups, respectively. The intention-to-treat eradication rates were 35.5,
      17.1, and 23.8% for the AOC7, FOT4, and FOT7 groups, respectively. CONCLUSION:
      Treatment regimens of 4 or 7 days are unacceptable for H. pylori infection in
      Iran, even in the presence of a favorable sensitivity profile.

PMID- 12519219
TI  - Relationship between non-steroidal anti-inflammatory drug use and Helicobacter
      pylori infection in bleeding or uncomplicated peptic ulcers: A case-control
      study.
AB  - BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drug (NSAID) use has been
      closely associated with an increased risk of bleeding peptic ulcers, while the
      prevalence of Helicobacter pylori infection has been reported to be lower in
      bleeding ulcers than in non-bleeding ones. However, whether an interaction exists
      between NSAID use and H. pylori infection has not clearly been elucidated yet.
      The aims of this study were to determine the frequency of NSAID use and H. pylori
      infection, to predict risk factors in bleeding peptic ulcers and to determine
      whether NSAID use and H. pylori infection interact with each other. METHODS:
      Ninety-six patients with bleeding ulcer were included in the study. The control
      group consisted of 106 patients with non-bleeding ulcer. Data were analyzed by
      using the chi-squared test, Fisher's exact test and logistic regression analysis
      with or without interaction term (H. pylori by NSAID). RESULTS: Non-steroidal
      anti-inflammatory drug use was significantly more common in patients with
      bleeding ulcers than in controls (79.2 vs 38.7%, unadjusted odds ratio (OR):
      6.02, 95% confidence interval (CI): 3.21-11.29). The frequency of the H. pylori
      infection was significantly lower in patients with bleeding ulcers than in
      controls (66.7 vs 89.6%, unadjusted OR: 0.23, 95% CI: 0.10-0.49). In the logistic
      regression analysis with the interaction term, male sex (adjusted OR: 3.70, 95%
      CI: 1.65-8.29), multiplicity of ulcers (adjusted OR: 4.10, 95% CI: 1.02-16.45)
      and NSAID use (adjusted OR: 33.87, 95% CI: 4.36-262.97) were independent risk
      factors for bleeding ulcers. There was a negative interaction between H. pylori
      and NSAID use (adjusted OR: 0.09, 95% CI: 0.01-0.83). CONCLUSIONS: The negative
      interaction between the two variables suggests that the presence of H. pylori is
      associated with a lower risk of bleeding in ulcer patients taking NSAIDs.

PMID- 12519220
TI  - Evaluation of two stool antigen tests for the detection of Helicobacter pylori
      infection in the Chinese population.
AB  - BACKGROUND AND AIM: The stool antigen test, the HpSA test, has been validated
      mainly in Western countries, but not properly in the Chinese population.
      Recently, another stool antigen test, the Apollo test, was developed, but its
      accuracy has rarely been validated. The aim of this study is to compare the
      accuracy of these two tests in the diagnosis of Helicobacter pylori infection in
      the Chinese population. METHODS: Consecutive dyspeptic patients referred for
      upper endoscopy were recruited. During endoscopy, biopsies were taken for the
      rapid urease test and histological examination as the gold standard. Stool
      specimens were collected and used for the HpSA and Apollo tests. RESULTS:
      Overall, 86 patients (39 males and 47 females, with a mean age of 55.8 years)
      were recruited. Helicobacter pylori infection was present in 44 (51%) patients as
      determined by the gold standard. The sensitivity, specificity and accuracy were
      86.4, 100, and 93.0%, respectively, for the HpSA, and 90.9, 97.6, and 94.2%,
      respectively, for the Apollo test when cases with equivocal results were
      considered as positive. In addition, agreement was achieved in 81 (94.2%) cases
      between the two tests, with a Kappa value of 0.887. CONCLUSION: Both the HpSA and
      Apollo tests achieve acceptable sensitivity and excellent specificity, with
      accuracies of over 90% for the detection of H. pylori infection in the Chinese
      population.

PMID- 12519221
TI  - Impaired expression of proteasome subunits and human leukocyte antigens class I
      in human colon cancer cells.
AB  - BACKGROUND AND AIM: The presentation of human leukocyte antigens (HLA) class I
      requires the coordinated expression of numerous components involved in antigen
      processing and antigen presentation. Tumor cells may alter the expression of
      these components to decrease HLA class I expression, allowing them to escape
      immune surveillance. The aim of this study is to investigate the expressions of
      these components, including proteasome subunits, and their involvement in the
      expression of HLA class I in human colon cancer cells. METHODS: Four human colon
      cancer cell lines, HCT116, SW403, LoVo and DLD-1, were used to examine the
      expression of HLA class I by flow cytometry. Reverse transcription-polymerase
      chain reaction was performed to assess the expression of beta2-microglobulin,
      heavy chains, transporter subunits, immunoproteasomes subunits and proteasome
      activator 28 (PA28) subunits. RESULTS: Human leukocyte antigen class I was
      expressed highly in HCT116 and SW403 cells and weakly in LoVo cells, but was not
      expressed in DLD-1 cells. The DLD-1 cells were deficient in the expression of
      proteasome subunits including low molecular weight polypeptide proteasome subunit
      2 (LMP2), multicatalytic endopeptidase complex-like-1 (MECL-1), PA28alpha and
      PA28beta, whereas other HLA class I-expressing cell lines expressed all
      components tested. gamma-Interferon (IFN-gamma) treatment of DLD-1 cells restored
      the expression of LMP2, MECL-1 and PA28beta, but not the expression of HLA class
      I. Enforced expression of PA28alpha induced the expression of HLA class I in IFN
      gamma-treated DLD-1 cells, but not in untreated DLD-1 cells. CONCLUSION: These
      results suggest that the impaired expression of proteasome subunits is involved
      in the loss of HLA class I expression in human colon cancer cells.

PMID- 12519222
TI  - Infrared spectrometry based 13C-octanoic acid breath test in measuring human
      solid gastric emptying.
AB  - BACKGROUND AND AIMS: Because of the convenience of non-dispersive infrared
      spectrometry (NDIRS), we attempted to validate the usefulness of NDIRS compared
      with scintigraphy in human solid gastric emptying (GE) measurement, and tried to
      establish the normal range of solid GE based on NDIRS. METHODS: Twelve healthy
      volunteers (three men, nine women) were recruited for simultaneous scintigraphy
      and 13C-octanoic acid breath test (13C-OABT) studies. Stomach half-emptying time
      (t1/2) and lag phase (tlag) were the two main GE parameters measured and
      correlated. The breath samples were analyzed using NDIRS every 10-15 min for a
      total of 6 h, while scintigraphy was taken minute by minute for the first 30 min,
      then hourly for 4 h. Another 32 healthy volunteers (19 men, 13 women) received
      only the 13C-OABT to measure their solid GE. RESULTS: A significant correlation
      for t1/2 was found between the breath test and scintigraphy (r = 0.85, P =
      0.001), while tlag was also positively correlated (r = 0.73, P = 0.007). The
      reference range of t1/2B based on all 44 subjects was 89.4-185.1 min (135.9 +/-
      21.1 min (mean +/- SD)), while the range for tlagB was 37.1-117.8 min (81.9 +/-
      17.4 min). No demographic characteristics were found to influence the GE
      parameters. CONCLUSIONS: 13C-octanoic acid breath test determined by NDIRS is a
      simple, non-invasive and reliable measurement, which may provide an 'office
      based' tool to detect solid GE.

PMID- 12519223
TI  - Sialyl Lewis X analog attenuates gastric microcirculatory disturbance and gastric
      mucosal erosion induced by thermal injury in rats.
AB  - BACKGROUND AND AIM: We hypothesize that selectins, which are adhesion molecules,
      are involved in the pathogenesis of stress-induced gastropathy. We therefore
      investigated whether the novel Sialyl Lewis X (SLex) analog, which is a
      clinically available antagonist of selectins, attenuate gastric mucosal lesions
      induced by thermal injury. METHODS: Male Wistar rats were anesthetized and a 30%
      full-skin thickness dorsal burn was inflicted on each rat. The SLex analog was
      administrated into the jugular vein 30 min before and 2.5 h after the thermal
      injury. Saline was administered to the vehicle group. The distribution of E
      selectin immunoreactivity on the luminal side of the gastric mucosal
      microvascular network was observed by immunohistochemical methods. Active oxygen
      species were measured by the chemiluminescence method. Rolling leukocytes and
      endothelial damage, investigated by using Monastral Blue B (MBB), of the gastric
      mucosal microvascular network were observed through an intravital microscope.
      RESULTS: A high intensity of E-selectin fluorescence was observed on the luminal
      surface of the venular endothelial cells 5 h after thermal injury in the vehicle
      group. However, E-selectin-associated fluorescence was almost negligible in the
      non-injury group and in the SLex analog group. The SLex analog also attenuated
      the rolling of leukocytes in the venules, venular deposits of MBB, luminol
      dependent chemiluminescence activities, and gastric mucosal lesion formation.
      CONCLUSION: It is suggested that the selectin family is involved in gastric
      microcirculatory disturbance and the pathogenesis of gastric mucosal lesions
      after thermal injury. A novel preventive therapy using the SLex analog is
      considered to effectively protect both gastric microcirculation and the gastric
      mucosa in rats with thermal injury.

PMID- 12519224
TI  - Examination of small bowel enzymes in chronic diarrhea.
AB  - BACKGROUND: In Indonesia, the proportion of daily carbohydrate intake is
      approximately 60-80%. A number of small bowel disorders can result in the
      impairment of absorption and enzyme deficiency. Chronic diarrhea is common in
      Indonesia. METHODS: Thirty-four functional dyspeptic patients with an
      endoscopically normal small bowel as a control group, and 17 chronic diarrhea
      patients from the Division of Gastroenterology, University of Indonesia/Cipto
      Mangunkusumo Hospital were included in this study. All patients underwent a
      gastroduodenojejunoscopy and an ileocolonoscopy examination. Biopsies were taken
      from the jejunum (two specimens) and the biopsy specimens were examined for
      enzyme analysis (lactase, maltase, sucrase). The data were analyzed by using the
      Kruskal-Wallis or anova. RESULTS: The lactase level of the chronic diarrhea group
      was significantly lower compared with that of the control group (1.941 +/- 1.621
      vs 2.502 +/- 2.098 micro mol/min mg protein; P < 0.001). The maltase level of the
      chronic diarrhea group was significantly lower compared with that of the control
      group (280.942 +/- 148.173 vs 371.920 +/- 250.177 micro mol/min mg protein; P <
      0.001). The sucrase level of the chronic diarrhea group was significantly lower
      compared with that of the control group (48.474 +/- 28.553 vs 66.727 +/- 49.685
      micro mol/min mg protein; P < 0.001). CONCLUSION: The enzyme activity
      concentrations (lactase, maltase, sucrase) were much lower in chronic diarrhea
      cases compared with the controls.

PMID- 12519225
TI  - Gastrointestinal dysmotility in patients with acute pancreatitis.
AB  - BACKGROUND AND AIMS: Gut-origin bacterial translocation is one of the major
      causes of pancreatic necrotic tissue infection in patients with severe acute
      pancreatitis (SAP). The gastrointestinal dysmotility is supposed to be the
      fundamental event in this process. To test this hypothesis, alteration of colonic
      transit time (CTT) in patients with acute pancreatitis (AP) was investigated. In
      order to evaluate the possible mechanisms involved in gastrointestinal
      dysmotility, changes of serum motilin (MTL), cholecystokinin (CCK) and vasoactive
      intestinal peptide (VIP) in patients with AP were also measured. METHODS: Twenty
      four non-consecutive patients with AP and 25 controls were included in this
      study. The diagnosis of AP was based upon clinical features, biochemical indices
      and radiological investigation. The severity of AP at admission was evaluated
      according to the APACHE-II and Balthazar computed tomography (CT) scoring system.
      Total and segmental CTT in patients with AP and in controls were determined by
      ingestion of radiopaque markers (Sitzmarks(R)) according to the modified
      Metcalf's method. Meanwhile, serum MTL and CCK were assessed using
      radioimmunoassay (RIA), and serum VIP was measured by using ELISA in this study.
      RESULTS: Compared to the controls, the total CTT and segmental CTT (mainly right
      and left hemicolon) were prolonged significantly in 10 patients with SAP and 14
      patients with MAP; P < 0.05. Moreover, the total CTT and segmental CTT were
      markedly more delayed in patients with SAP than in patients with MAP; P < 0.05.
      The concentrations of serum MTL and CCK were significantly decreased in both MAP
      and SAP patients compared with those in controls (P < 0.01). There was no
      significant differences in serum MTL and CCK levels between the SAP and MAP
      groups; P > 0.05. In addition, the concentration of serum VIP was increased in AP
      patients, and it reached statistical significance in patients with SAP (P <
      0.05). CONCLUSIONS: In conclusion, gastrointestinal dysmotility often occurred in
      patients with AP, especially more severely in SAP patients. One of the possible
      mechanisms might be related to the synergic actions of gut hormones, such as MTL,
      CCK and VIP.

PMID- 12519226
TI  - Relationship between human leukocyte antigen-DRB1 and autoimmune hepatitis type I
      in Chinese patients.
AB  - AIM: To analyze the association of human leukocyte antigen (HLA)-DRB1 with
      autoimmune hepatitis type I (AIH) among Chinese patients in the Shanghai area.
      METHODS: In 32 patients and 48 healthy controls, polymerase chain reaction
      amplified with sequence-specific primers (PCR-SSP) was performed to elucidate the
      relevance of certain alleles or polymorphic sequences of HLA-DRB1 with autoimmune
      hepatitis. RESULTS: The HLA-DRB1 typing by PCR-SSP showed that DR4 had a
      significantly increased frequency among patients with AIH versus that of healthy
      controls (46.9 vs 20.8%; relative risk = 3.35, P = 0.014). In the subtypes of
      DR4, there was a trend of an increase in the gene frequency of DRB1*0405 in
      patients with AIH versus that of healthy controls (21.9 vs 6.3%, P = 0.04, but
      corrected P (Pc) = 0.08). In addition, our analysis indicated a significant
      increase in the alleles frequency encoding Leu-Leu-Glu-Gln-Lys-Arg (LLEQRR) from
      the third hyperpolymorphic region (HVR3) of DR4 in the patients with AIH (86.7%
      of DR4 positive patients vs 40.0% in DR4 positive controls, P = 0.016, Pc =
      0.028, relative risk (RR) = 9.75). CONCLUSION: Type I AIH among Chinese patients
      is associated with HLA-DR4. There is a relevance of type I AIH and LLEQRR
      sequence within the third hyperpolymorphic region of the DRB1 allele.

PMID- 12519227
TI  - Prediction of relapse after interferon therapy in hepatitis C virus-infected
      patients by the use of triple assay.
AB  - BACKGROUND AND METHODS: In recent years, several tests have been used as
      predictive factors for relapse after the end of interferon therapy of chronic
      hepatitis C carriers. Serum hepatitis C virus (HCV)-RNA has proved insensitive
      for predicting relapse because more than 50% of patients with undetectable
      reverse transcription-polymerase chain reaction (RT-PCR) levels of HCV at the end
      of therapy become positive for viral RNA after interferon withdrawal. The
      detection of a minus RNA strand of HCV in liver also failed to efficiently
      predict relapses in chronic hepatitis patients. Furthermore, the use of a whole
      blood assay of HCV-RNA has been controversial. We used a triple assay comprised
      of RT-PCR tests for the detection of HCV-RNA plus strand in serum and peripheral
      blood mononuclear cells (PBMC), together with testing for the minus strand in
      PBMC for prediction of relapse after interferon + ribavirin combination therapy
      in 45 patients with chronic hepatitis C. RESULTS: The only four patients with a
      negative triple assay had no relapse 1 year after the end of therapy. In
      contrast, two-thirds of the 12 patients who tested negative for viral RNA in
      serum at the end of therapy relapsed 1 year later. CONCLUSION: We concluded that
      the absence of both minus and plus strands in patients who tested negative for
      serum PCR may indicate the total eradication of HCV.

PMID- 12519228
TI  - In vitro binding of hepatitis C virus to CD81-positive and -negative human cell
      lines.
AB  - AIM: The aim of the present study is to study the mechanism of entry of hepatitis
      C virus (HCV) into human cells. We examined the in vitro binding of HCV to
      various human cell lines with or without CD81 expression. METHODS: We first used
      three cell lines, two hepatocyte-derived, huH-7 and HepG2, and one colon cancer
      cell line, Cw2. Among them, HepG2 did not express TAPA-1 (CD81) on their surface
      but two others did. They were incubated with HCV + serum for 1 h and HCV-RNA in
      extracted RNA obtained from these cells was examined by using both a quantitative
      test and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: We
      found that a significant amount of HCV-RNA was detected in huH-7 and HepG2 but
      not in Cw2. In addition, the titer of HCV-RNA in serum-incubated CD81-transfected
      HepG2 was similar to that of the non-transfected titer, and the binding between
      HCV and huH-7 was not inhibited by anti-CD81. Under the same condition, HCV-RNA
      tended to be detectable in serum-pulsed hepatocyte-derived cell lines, but not in
      the others. CONCLUSION: These results suggest that while CD81, as reported,
      specifically binds to HCV-E2 protein, the entry of HCV into human hepatocytes
      might be regulated by CD81-unrelated molecule(s).

PMID- 12519229
TI  - Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model: A
      sequential pathological evaluation.
AB  - BACKGROUND: The introduction of transgenic technology has made it possible to
      study the steps of carcinogenesis and directly establish the link between viral
      subgenomic fragments and specific types of cancer. Research directed at hepatitis
      B virus (HBV)-related carcinogenesis has benefited from this technology. We
      present a detailed pathological evaluation of the sequential steps of
      hepatocarcinogenesis in a hepatitis B 'x' (HBx) transgenic mouse model. In this
      model, the transgene incorporates the region encoding amino acids 58-154 of the
      HBV X protein and the murine c-myc gene. This model demonstrated changes in the
      liver from birth with foci of multicentric dysplasia evolving into nodules and
      overt hepatocellular carcinoma between 20 and 28 weeks. METHODS AND RESULTS: The
      hepatocytes were mitotically active and showed increased proliferative capacity
      soon after birth, with exponential increase thereafter. This was accompanied by a
      high rate of apoptosis, which later declined as the tumors developed. Other
      functional and immunophenotypic characteristics included a high c-myc expression
      in the neoplastic lesions, no alteration in p53 expression, and no alteration in
      the expression of hepatic enzymes except for diffuse expression of succinic
      dehydrogenase. CONCLUSION: The entire process illustrates the disturbances of
      cell growth and death because of the collaborative influence of HBx and c-myc
      genes that result in the development of hepatocellular carcinoma after a
      prolonged latent period.

PMID- 12519230
TI  - Contrast media-enhanced power Doppler sonography for evaluation of hemangiomas
      and malignant tumors in the liver.
AB  - AIM: To evaluate the characterization of liver hemangiomas and malignant tumors
      using power Doppler sonography before and after intravenous injection of a
      sonocontrast agent. METHODS: Forty-five patients with 57 liver tumors (22
      hemangiomas, 24 metastases, 10 hepatocellular carcinomas (HCC) and one
      cholangiocellular carcinoma) were examined prospectively. The distribution
      (peripheral, central, mosaic) and extent (none, minimal, moderate and strong) of
      intratumoral flow pattern in each sonographic examination was subjectively
      classified. RESULTS: The administration of the sonocontrast agent by bolus
      injection caused enhancement to gradually increase up to 2 min and lasted for 4-5
      min. After injection of contrast agent, flow signals appeared or increased in 34
      tumors. No signal enhancement was observed in 18 hemangiomas, four metastases and
      one HCC. The sensitivity and specificity of intratumoral vascularity for the
      detection of malignant liver tumors was 37.1 and 90.9% for unenhanced power
      Doppler sonography, and 85.7 and 81.8% for contrast-enhanced power Doppler
      sonography, respectively. CONCLUSION: Contrast-enhanced power Doppler sonography
      is superior to unenhanced power Doppler sonography in the demonstration of
      malignant tumor vascularity, and is helpful in differentiating between
      hemangiomas and malignant liver tumors. A specific flow pattern within the tumor
      is not established in primary and metastatic malignant tumors with contrast
      enhanced power Doppler sonography.

PMID- 12519231
TI  - Preoperative assessment of hepatic function: Utility of a new convenient two
      compartment model analysis using galactosyl human serum albumin scintigraphy.
AB  - BACKGROUND AND AIM: Preoperative hepatic function was evaluated using technetium
      99 m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin (Tc-GSA)
      and a scintillation camera to detect hepatic Tc-GSA uptake by the
      asialoglycoprotein receptor. METHODS: Sixty-two preoperative patients with liver
      cancer, including hepatocellular and cholangiocellular carcinomas, were studied,
      using two-parameter two-compartment model analysis. This model is simpler than
      either the three- or five-compartment model, both of which are accurate but which
      require complicated analysis and enormous calculation. The parameters k1 and k2
      represented the transfer rate constant from the blood to the liver and from the
      liver to the blood, respectively. We calculated k1, k2, and k1/k2 from time
      radioactivity curves of the heart and liver as well as VLmg, which represented
      the maximal amount of Tc-GSA in the liver. RESULTS: The results were compared to
      those of conventional liver function analysis using Tc-GSA (the index of blood
      clearance (HH15) and the receptor index (LHL15)) or indocyanine green (ICGR15).
      Both HH15 and LHL15 were significantly correlated with k1, k1/k2, and VLmg. In
      addition, they closely correlated with the results of ICGR15 and some serum
      hepatic function tests (aspartate aminotransferase, choline esterase, albumin,
      platelet). The pathological grading for liver cirrhosis also correlated with k1,
      k1/k2, and VLmg. From a clinical point of view, VLmg had a significant
      correlation with the Child-Pugh score. CONCLUSIONS: These results suggest that
      this new compartment analysis will be useful in evaluating liver function, as it
      is accurate, simple and convenient.

PMID- 12519232
TI  - Hepatobiliary and pancreatic: Primary rabdomyosarcoma of the liver.

PMID- 12519233
TI  - Gastrointestinal: Abdominal distension in irritable bowel syndrome.

PMID- 12519234
TI  - A case of pseudotumorous pancreatitis that presented unique pancreatoscopic
      findings with the peroral electronic pancreatoscope.
AB  - A 49-year-old man was admitted to Hospital of Kyoto Prefectural University of
      Medicine complaining of epigastralgia and jaundice. There was a tumor
      (approximately 30 mm) in the pancreatic head on ultrasound, computed tomography
      and magnetic resonance imaging. Endoscopic retrograde cholangiopancreatography
      revealed a stenosis of the main pancreatic duct in the head of the pancreas.
      Pancreatoscopy with the peroral electronic pancreatoscope (PEPS) was performed to
      differentiate between pseudotumorous pancreatitis (PTP) and pancreatic carcinoma.
      The PEPS showed non-erosive erythematous mucosa around the stenosis and this
      unique finding was different from that of pancreatic carcinoma. Pylorus
      preserving pancreatoduodenectomy was performed under the possible diagnosis of
      carcinoma. As a result, the diagnosis of PTP was confirmed histopathologically.
      At present, the diagnosis of PTP is difficult because of similar findings with
      carcinoma in various imaging procedures. However, we consider that detailed
      observation and accurate morphologic assessment of the main pancreatic duct with
      the PEPS has the possibility of differentiating PTP from pancreatic carcinoma.

PMID- 12519235
TI  - Management of bleeding from gastric fundal varices.

PMID- 12519236
TI  - Giant hepatic hemangioma mimicking hepatocellular carcinoma.

PMID- 12519237
TI  - Gastric adenocarcinoma with Sister Mary Joseph's nodule successfully treated with
      combined chemoradiation.

PMID- 12519238
TI  - Of germs in inflammatory bowel disease and of how to fight them.

PMID- 12519239
TI  - Successfull response to alpha 2b interferon plus ribavirin associated with
      venesectomies in a patient with chronic hepatitis C and genetic hemochromatosis.

PMID- 12519243
TI  - Adolescent access to emergency contraception in A and E departments: reviewing
      the literature from a feminist perspective.
AB  - Recent moves in parts of UK to provide opportunities for 'over the counter'
      purchasing at pharmacies, has meant that access to emergency oral hormonal
      contraception for adolescents is undergoing something of a revolution. The
      provision of emergency contraception (EC) to adolescents in Accident and
      Emergency (A and E) departments, however, is nothing new and is now an
      established component of the current government objective to reduce teenage
      pregnancy rates in this country. The tensions apparent in A and E departments
      related to the provision of EC, particularly to adolescents, have recently been
      recognized, but little attention has been paid to analysing the reasons why such
      tensions might exist. This article is based on a literature review carried out as
      part of a study of nurses' encounters with adolescents accessing EC in A and E
      departments in the North-west of England. It is a reappraisal of the salient
      issues in this arena from a feminist perspective, aiming to provide an
      alternative with which to view the encounter between adolescents and service
      providers in A and E.

PMID- 12519246
TI  - Using cost-effectiveness analysis to compare Hospital at Home and in-patient
      interventions. Part 2.
AB  - An economic analysis was conducted as an integral part of a comparison of the
      effectiveness and suitability of Hospital at Home (HaH) and in-patient
      interventions. The sample comprised 109 adult primary total joint replacement
      patients and 21 of their co-resident informal carers. Part 2 is principally a
      methodology paper and describes how nurses may use a variety of methods to
      compare cost between treatment modalities. A Cost-Effectiveness Analysis
      framework uses the data from Paper 1 to calculate the economic feasibility of HaH
      compared with traditional in-patient interventions as a worked example of how the
      principles of economic analysis can be used within health care research. The
      basic information for calculating cost of both interventions was obtained by
      multiplying the mean length of total treatment days by the cost per treatment
      day. However calculating and comparing cost for in-patient and HaH modalities was
      multifaceted and included costs incurred by patients and families as well as any
      shift in cost from tertiary to community and outpatient services. Application of
      the cost-effectiveness analysis framework demonstrated that not only was HaH more
      effective than in-patient care in several aspects, but also it was less costly
      because of a mean reduction in length of stay of 0.9 days per patient and a
      significant reduction in cost per treatment day because of removal of hospital
      overhead costs and reduced special duty payments even when offset against
      additional transport, community and outpatient costs.

PMID- 12519245
TI  - Using cost-effectiveness analysis to compare Hospital at Home and in-patient
      interventions. Part 1.
AB  - An economic analysis was conducted as an integral part of a comparison of the
      effectiveness and suitability of Hospital at Home (HaH) and in-patient
      interventions. The sample comprised of 109 adult primary total joint replacement
      patients and 21 of their coresident informal carers. The paper is presented in
      two parts. Part 1 includes the background and rationale for the study and the
      findings from the comparison of the effectiveness of the two interventions using
      multiple data collection sources. Data were collected using questionnaires, audit
      and semi-structured interviews. Hospital at Home was found to be significantly
      more effective in terms of patient satisfaction and reduced joint stiffness and
      as least as effective as in-patient care in relation to levels of joint pain,
      joint disability and incidence of postoperative complications. In addition
      informal carers reported 107 positive comments compared with 36 negative comments
      related to HaH care and all except one of the 21 carers would choose HaH again in
      preference to in-patient care.

PMID- 12519247
TI  - Referrals from home care to emergency hospital care: basis for decisions.
AB  - The Swedish government implemented a reform, the Adel reform, in the care of
      older citizens in 1992, so that the communities where older people live became
      responsible for their care and housing. Nurses were appointed to make sure that
      older people were given accurate care and to act as supervisors for nurses'
      aides. In this study, 10 Registered Nurses from community home care services and
      four consultant head physicians in primary care were interviewed in order to
      illuminate what they thought influenced nurses' decisions to refer patients for
      emergency treatment and what support they requested to facilitate the decision.
      Content analysis showed the necessity of feeling secure in one's role as a
      community nurse. The categories that developed were: own competence, knowledge
      about the patient and a supportive working environment. The main theme was To
      feel safe in one's role - a basis for decision-making. High demands were put on
      the nurses' competence and their burden of responsibility became too great. This
      influenced decision-making negatively, if nurses felt that they were lacking in
      their own personal competence. Training in documentation for the nurses was
      required, as well as the need for organizations to provide staff with sufficient
      time for accurate documentation. A greater input of nursing and medical care was
      required to make it possible for patients to be cared for at home if they so
      wished. Respondents described considerable deficiencies in their working
      environment and in co-workers' competence, and nurses' professional roles within
      the community were not made clear. If these problems were remedied, this would
      improve working conditions, increase understanding, and reduce feelings of
      uncertainty among decision-makers.

PMID- 12519248
TI  - Telephone nurses' experience of problems with telephone advice in Sweden.
AB  - By telephoning a healthcare call centre, individuals in Sweden can consult a
      nurse to discuss medical problems and health care accessibility, and to receive
      professional information on how to find their way about the health care system.
      The aim of the study was to identify problems, difficulties and disadvantages
      that telephone nurses with varying degrees of experience had met during their
      professional careers. The Delphi technique was used with three sets of
      questionnaires. Twenty-five nurses with varying experience of working with
      telephone advice from six 24-hours call centres participated in the study. The
      response rate was 100%. An open-ended question generated 154 statements. Comments
      were categorized into 24 different problem categories. Ten problem categories
      were mainly related to the nurse perspective, i.e. the problems experienced were
      associated with the qualities of the nurse, eight principally to the patient
      perspective, i.e. problems associated with caller characteristics and six mostly
      to the organizational perspective, i.e. problems linked to the organization of
      the national health service. 'Lack of health care resources' was rated as the
      biggest problem, 'second-hand consultations' as the second and 'always making a
      decision' as the third biggest problem. Decision-making seems to be the core of
      telephone advice nursing and problems related to the nurses, patients and
      organization seem to influence the telephone nurses' working situation. Training
      should focus on active listening and handling social conflicts.

PMID- 12519249
TI  - Health promotion practices of older adults: testing an individualized approach.
AB  - The world's population is getting older. Consequently, the World Health
      Organization has focused efforts on health promotion activities for these
      individuals. The purpose of this study was to explore the factors that influence
      health promotion behaviours and to describe the impact of an individualized
      approach to decision-making with regard to health promotion activities in a group
      of older adults living in a continuing care retirement community. The study used
      a single group pre- and post-test design that included a total of 134 residents.
      Descriptive statistics were used to describe the sample. A McNemar test was used
      to compare health promotion activities pre- and postintervention. Regression
      analysis was used to consider the factors that influenced health promotion
      activities in these individuals. The survey included questions about health
      promotion activities and both mental and physical health status. In the year
      between baseline and follow-up testing a geriatric nurse practitioner provided
      both formal and informal education about health promotion activities. With the
      exception of monitoring dietary fat intake, there was not a statistically
      significant difference in primary and secondary health promotion behaviours pre-
      and post-testing. There was, however, a decline in smoking and alcohol use, an
      increase in physical activity and a slight decline in the percentage of older
      adults who engaged in cancer screenings. An individualized approach may be a
      useful way to help older adults make health decisions and engage in those health
      promotion activities that will increase their quality of life.

PMID- 12519251
TI  - Quality of life as a concept for developing learning disability nursing practice?
AB  - This paper offers a critical examination of how the concept of Quality of Life
      might be used to enhance learning disability nursing practice. Quality of Life
      will increasingly influence the provision and evaluation of services and practice
      in the field of learning disability. Attempting to define and assess Quality of
      Life is, however, problematic because of the complexity and multidimensional
      nature of the concept. The use of domains to measure Quality of Life is advocated
      by many researchers for both objective and subjective measures and use of Quality
      of Life as an evaluation tool is seen as a way of improving the life quality of
      people with learning disabilities. However, there are concerns that the use of
      such an approach could perpetuate professional agendas rather than empower people
      with learning disabilities themselves. To date, Quality of Life approaches have
      not had a major impact on learning disability nursing. However, it is suggested
      that they can be helpful as sensitizing concepts, a basis for collaborative care
      planning and a framework for evaluation. Recommendations are made for education,
      practice and research.

PMID- 12519252
TI  - District nurses' experiences of providing care in residential care home settings.
AB  - Little research describes the involvement and contribution of primary health care
      services in residential homes, despite policy and research concerns that older
      people in residential homes are a vulnerable population for whom care must be
      improved. The aim of this research was to explore the actual and potential
      contribution of primary care nurses in residential homes for older people,
      particularly district nurses. Five focus groups were held with district nurses in
      one county in England, to explore how participants represented their views,
      values and experiences of working in residential homes. Our major finding was the
      importance of context in shaping the experience of district nursing involvement.
      General practitioner attachment determined the frequency of visiting homes and
      affected workload. District nurses had regular contact with residential homes for
      discrete nursing tasks, but appropriateness of referrals and input was not
      agreed. The focus group discussions with district nurses revealed how problematic
      their work in residential homes was and a lack of consensus about their role. The
      data suggested that uncertainty about providing care in a setting that straddles
      the health and social care, public and private divide, and anxieties about
      managing their workload overshadowed their acknowledged concerns about the older
      people in residential care homes. Further research is needed to substantiate the
      findings, obtain residents' views and address issues of how to achieve integrated
      and equitable health and social care for this group.

PMID- 12519253
TI  - Hierarchy of evidence: a framework for ranking evidence evaluating healthcare
      interventions.
AB  - A number of hierarchies of evidence have been developed to enable different
      research methods to be ranked according to the validity of their findings.
      However, most have focused on evaluation of the effectiveness of interventions.
      When the evaluation of healthcare addresses its appropriateness or feasibility,
      then existing hierarchies are inadequate. This paper reports the development of a
      hierarchy for ranking of evidence evaluating healthcare interventions. The aims
      of this hierarchy are twofold. Firstly, it is to provide a means by which the
      evidence from a range of methodologically different types of research can be
      graded. Secondly, it is to provide a logical framework that can be used during
      the development of systematic review protocols to help determine the study
      designs which can contribute valid evidence when the evaluation extends beyond
      effectiveness. The proposed hierarchy was developed based on a review of
      literature, investigation of existing hierarchies and examination of the
      strengths and limitations of different research methods. The proposed hierarchy
      of evidence focuses on three dimensions of the evaluation: effectiveness,
      appropriateness and feasibility. Research that can contribute valid evidence to
      each is suggested. To address the varying strengths of different research
      designs, four levels of evidence are proposed: excellent, good, fair and poor.
      The strength of the proposed hierarchy is that it acknowledges the valid
      contribution of evidence generated by a range of different types of research.
      However, hierarchies only provide a guide to the strength of the available
      evidence and other issues such as the quality of research also have an important
      influence.

PMID- 12519254
TI  - Differences and similarities in the perception of caring between Spanish and UK
      nurses.
AB  - The aim of the present paper was to compare and contrast perceptions of caring in
      nursing between Spanish and UK nurses. There are no previous studies comparing
      directly the perceptions of caring across cultures in nursing. A survey method
      was used employing the 25-item Caring Dimensions Inventory. Data were Mokken
      scaled for comparison with data from a previous study and scores for common items
      on the 25-item Caring Dimension Inventory for Spanish and UK nurses were
      correlated. There were similarities and differences between Spanish and UK
      nurses' perceptions of caring: many similar items were incorporated into Mokken
      scales but the endorsement of items did not correlate. The present work
      demonstrates that it is possible to measure differences and similarities in
      perceptions of caring. The study design could be improved and such work could be
      valuable in cross-cultural work with nurses.

PMID- 12519255
TI  - Video home training as a method of supporting family life control.
AB  - The purpose of this study was to describe video home training as a method of
      early support in problems of family life control. Answers were sought to the
      following questions: how does a family counsellor use video home training to
      support families' own resources and family life control, and what are the uses
      and benefits of video home training from parents' perspective? The data consisted
      of the videotaped counselling sessions and family service plans for five
      families, and were analysed using the general method of analysing photographs and
      video material developed by anthropologist-photographers. Video home training as
      a method in supporting family life control consisted of goal-orientated
      reflection by parents on videotaped episodes of their everyday family life under
      the guidance of a family counsellor. The process of videotaping family life, in
      depth analysis of the videotapes, recognition of instances of successful
      interaction, and search for new alternatives gave participants a feeling that it
      would be possible for them to make their everyday life fluent and functional. The
      findings show that video home training helped the families to gain better control
      over their family life.

PMID- 12519256
TI  - 'Understanding and being understood' as a creative caring phenomenon--in care of
      patients with stroke and aphasia.
AB  - Five care providers particularly successful at communicating with patients with
      communication difficulties were video-recorded together with three patients with
      aphasia after stroke, during morning care activities. The care providers were
      then interviewed immediately after the video-recordings, about their experiences
      of communicating with such patients. The interviews with the care providers were
      interpreted by means of a phenomenological hermeneutic method. Co-creating was
      the main theme found. Care providers invite the patient to participate in the
      creative act of communication. They have a communicative attitude and show
      interest in the patients' personal desires. The care providers encounter the
      patient as a presence in a caring communion. In part, care providers communicate
      by continuously conveying their presence to the patient and even creating
      availability in a close and open intersubjective relationship. A relaxed and
      supportive atmosphere facilitates reciprocity between care provider and patient.
      The communication is not technical or strategic; instead care providers share the
      patients' experiences in a silent dialogue. This silent dialogue involves sharing
      the patients' feelings and thus receiving messages from the patient.

PMID- 12519257
TI  - The relationship of perceived control to outcomes in older women undergoing
      surgery for fractured neck of femur.
AB  - This paper examines the relationship between internal locus of control and
      recovery from surgery for fractured neck of femur in women over the age of 65
      years, in order to inform strategies for nursing care. Structured interviews were
      carried out at 5 and 30 days postsurgery with 112 women (mean age 78.6 years) in
      five general hospitals in the North of England. Locus of control was assessed as
      a factor associated with the outcomes of physical disability (measured as
      dependence in activities of daily living) and psychological distress (measured
      using the Hospital Anxiety and Depression Scale). Internal locus of control was
      significantly related to less physical disability, but no association was found
      between locus of control and depression and anxiety at 30 days postsurgery when
      age, 5-day measures and other 30-day outcome measures were controlled. The
      findings suggest that nursing interventions that enhance perceived internal
      control by patients during rehabilitation may result in better physical outcomes.
      Further work is required to explore the relationship of control to psychological
      outcomes.

PMID- 12519258
TI  - Changes in practice at the nurse-doctor interface. Using focus groups to explore
      the perceptions of first level nurses working in an acute care setting.
AB  - A unique combination of factors has recently triggered a rapid change in the
      clinical practice of nurses in the UK. This study was carried out to explore the
      consequences of changing practice at the nurse-doctor interface, as perceived by
      first level nurses working in an acute care setting in the UK. Qualitative data
      were collected using focus group interviews and analysed thematically. Findings
      suggest that role change to these nurses is represented by a 'shift' in the
      practice of technical activities from junior doctors and a corresponding
      delegation of nursing activity to care assistants. It is suggested that the
      wholesale incorporation of technical interventions into the role of the nurse
      without an increase in the number of qualified nurses is turning nursing back to
      a task system of care delivery. This has the potential to depersonalize patients
      and reduce work satisfaction for nurses.

PMID- 12519259
TI  - Assessing student nurse clinical competency: will we ever get it right?
AB  - In 1997, a revised system was introduced at the University of Glamorgan, Wales,
      to assess student nurse clinical competency. This was firstly as a result of
      concerns that the previous system was based on limited documentary evidence, and,
      secondly as the Welsh National Board for Nursing and Midwifery issued new
      competency statements. This article reports an evaluative research study which
      aimed to determine whether the revised system was an effective measure of
      clinical competency. A series of focus groups were conducted with students,
      tutors and clinical preceptors to discuss their experiences of using the revised
      system. A content analysis was conducted of all evidence written by students to
      support the achievement of clinical competency. The findings of the focus groups
      indicated that each group had some initial problems with the assessment process.
      The main concern for all groups was lack of consistency and uncertainty in the
      assessment process. Although the introduction of written evidence to support
      clinical competency was welcomed, many felt that too much evidence was required.
      Content analysis of competency documentation aimed to compare student evidence
      and to determine whether there were inconsistencies in the assessment process.
      There were many variations in the evidence obtained from students, in particular
      the amount of evidence written by each student. The findings clearly indicate
      that further revisions are necessary to ensure that the system is implemented in
      the most effective way. The Fitness for Practice report (UKCC, 1999) has ensured
      that competency-based assessment is here to stay in the UK. Evaluative research
      of this type is important to ensure that we adopt the most suitable approach to
      assessing clinical competency.

PMID- 12519260
TI  - Changes in self-esteem during a 3-year pre-registration Diploma in Higher
      Education (Nursing) programme.
AB  - Nurses' self-esteem affects patient care. This study measured self-esteem of pre
      registration nursing students over their 3-year training programme. Quantitative
      data were measured by the Professional Self-Concept Nursing Inventory and the
      Tennessee Self-Concept Scale. Students's self-esteem decreased during their
      training programme. Results indicate a need to address the damaging effects of
      the process of becoming a nurse.

PMID- 12519261
TI  - Perceived stress and sense of coherence among critical care nurses in Hong Kong:
      a pilot study.

PMID- 12519262
TI  - An investigation into night-time self-turning by nursing home residents.

PMID- 12519263
TI  - Social stigma as a barrier to diabetes self-management: implications for multi
      level interventions.

PMID- 12519270
TI  - Effectiveness of home-based cardiac rehabilitation for special needs patients.
AB  - BACKGROUND: The benefits of cardiac rehabilitation programmes have been well
      documented including reductions in mortality, improved physical performance, and
      improved quality of life. However, a large number of special needs patients often
      fail to access these programmes. Of particular concern are elderly patients with
      chronic illness and disability. AIMS: To evaluate the effectiveness of a home
      based cardiac rehabilitation programme in improving health outcomes and
      rehabilitation access for special-needs patients. DESIGN: Using a one-group pre
      and post-test quasi-experimental design 40 elderly patients recently discharged
      from hospital following a cardiac event completed the Short Form Health Survey,
      the Angina Quiz, and the Exercise Assessment Questionnaire prior to undertaking
      home-based rehabilitation. The rehabilitation programme consisted of four
      community nursing contacts over a 9-week period primarily aimed at individual
      patient education and carer support. ANALYSIS: Descriptive statistics provided
      analysis for demographic data. Repeated measures multivariate analysis of
      variance (manova) were computed to examine changes in health-state and practices.
      RESULTS: Significant positive changes were found for measures of quality of life,
      knowledge of angina, and exercise tolerance. Additionally, the higher levels of
      participation and completion by older women was encouraging. Development of carer
      competence through an improved knowledge base and nursing support was also
      evident. LIMITATIONS: While theoretically defensible positive outcomes were found
      these results need to be replicated in a larger study. Similarly, the limitations
      imposed by a single group pretest, post-test design suggest that claims of
      generalizability need to be limited to the specific variables measured in this
      study. CONCLUSION: The study demonstrated medium term positive health outcomes.
      These positive findings suggest that home-based rehabilitation using larger
      samples of older patients with comorbidities, and using randomized comparative
      group designs, may be a fruitful area in future research.

PMID- 12519271
TI  - The effectiveness of Watson's Caring Model on the quality of life and blood
      pressure of patients with hypertension.
AB  - BACKGROUND: Nurses caring relationships with hypertensive patients can have a
      positive effect upon their blood pressure and may increase quality of life and
      prolongation of life. Hypertension affects a large number of people. It is
      important that those affected receive, in addition to the best available medical
      treatment, nursing care that best meets their needs and adds to the quality of
      their lives. Watson's Caring Model is one nursing approach consistent with needs
      of persons with hypertension, and was used in this study to guide both research
      and practice. AIM: To determine the effectiveness of a nurse's caring
      relationship according to Watson's Caring Model on the blood pressure and the
      quality of life of patients with hypertension. METHODS: The design of the study
      was a one-group pretest and post-test. The study included 52 patients with
      hypertension in four health care units in Erzurum, Turkey in 2000. These patients
      had been diagnosed with hypertension and invited to participate in a research
      project involving nursing care. After acceptance, patients were given
      questionnaires consisting of demographic characteristics; their blood pressure
      was measured, and a quality of life scale was administered. Each of the
      participating nurse researchers was prepared in the use of Watson's Theory and
      Model of Caring (and the 10 Carative Factors). This training formed the basis of
      the caring process used by the nurse researchers who then visited the patients
      and their families once a week for blood pressure measurement for a 3-month
      period. At the end of care, the quality of life scale was applied to patients,
      and blood pressures were measured as the post-test. RESULTS: There were
      statistically significant differences between mean scores of general well-being
      (t = 3.097, d.f. = 51, P = 0.003), physical symptoms and activity (t = 2.994,
      d.f. = 51, P = 0.004), medical interaction (t = 2.127, d.f. = 51, P = 0.035).
      There were also significant differences between blood pressure (systolic: t =
      4.830, d.f. = 51, P = 0.000; and diastolic: t = 3.51, d.f. = 51, P = 0.001) in
      pre- and post-test. CONCLUSION: This study demonstrated a relationship between
      care given according to Watson's Caring model and increased quality of life of
      the patients with hypertension. Further, in those patients for whom the caring
      model was practised, there was a relationship between the Caring model and a
      decrease in patient's blood pressure. The Watson Caring Model is recommended as a
      guide to nursing patients with hypertension, as one means of decreasing blood
      pressure and increase in quality of life.

PMID- 12519272
TI  - Australian nurses' and midwives' knowledge of computers and their attitudes to
      using them in their practice.
AB  - BACKGROUND: The introduction of a new information retrieval system for the use of
      health service staff at a large tertiary referral hospital provided an excellent
      opportunity for nurses to make greater use of evidence to inform their practice.
      However, the extent to which nurses were able to access the resource was unknown.
      AIM: The aim of the study was to obtain this information and to test nurses'
      knowledge of computers and their attitudes to using them in their practice.
      METHODS: During October 2001 a computer use questionnaire was attached to the pay
      advice slips of all nursing staff at the Royal Brisbane and Royal Women's
      Hospital (n = 1708). Staff were asked to return their completed questionnaire in
      a preaddressed return envelope. To encourage this, a prize (a Gold Class cinema
      pass for two) was offered. RESULTS: Of the 1708 questionnaires distributed, 590
      were returned, giving a 34.5% response rate. Computer use was influenced by
      education, nursing seniority, age, and length of time in the service and, to a
      lesser extent, gender. CONCLUSIONS: Information from the study has assisted
      planners and educators to identify clusters of nurses to target for interventions
      in this area. Results will also be used to assess the success of any
      interventions.

PMID- 12519273
TI  - Obesity in people with intellectual disabilities: the impact of nurse-led health
      screenings and health promotion activities.
AB  - BACKGROUND: Obesity appears to be more common among people with intellectual
      disabilities, with few studies focusing on achieving weight reduction. AIM:
      Firstly, to follow-up people identified as overweight and obese following special
      health screening clinics and to determine the actions taken. Secondly, to
      evaluate the impact of health promotion classes on participants' weight loss.
      METHODS: A clinic led by two learning disability nurses was held for all people
      aged 10 years and over (n = 464) who attended special services within the area of
      one Health and Social Services Trust in Northern Ireland. In a second study, the
      nurses organized health promotion classes for 20 people over a 6- or 8-week
      period. FINDINGS: The health screen identified 64% of adults and 26% of 10-19
      year olds as being overweight or obese. Moreover, those aged 40-49 years who were
      obese had significantly higher levels of blood pressure. However, information
      obtained from a follow-up questionnaire sent after 3 months suggested that of the
      122 people identified for weight reduction, action had been taken for only 34% of
      them and only three were reported to have lost weight. The health promotion
      classes, however, led to a significant reduction in weight and body mass index
      scores. CONCLUSIONS: Health screening per se has limited impact on reducing
      obesity levels in this client group. Rather, health personnel such as general
      practitioners, nurses and health promotion staff need to work in partnership with
      service staff, carers and people with intellectual disabilities to create more
      active lifestyles.

PMID- 12519274
TI  - Limit-setting and decision-making in the management of aggression.
AB  - BACKGROUND: Several published research studies have suggested that inpatient
      aggression against nursing staff may be directly precipitated by common nurse
      patient interactions. This study sought to examine the structure of nurses'
      judgements in situations of conflict. METHOD: Seventy practising United Kingdom
      psychiatric nurses were presented with a number of conflict scenarios and were
      asked to rate a range of intervention options for each scenario according to how
      appropriate they perceived those interventions to be. Their responses were
      analysed using multidimensional scaling techniques. RESULTS: The results suggest
      that issues associated with limit setting and autonomy were perceived as most
      important by the nurses and that these issues are most likely to lead to
      disagreements in judgement between nurses of different status. Nurses of higher
      grades (levels) showed a significantly greater preference for respectful and
      autonomy-confirming interventions than their more junior nurses. These results
      have training and policy implications and further research should examine the
      effects of such nursing judgements on patient care.

PMID- 12519275
TI  - Poorly served? Eating and dementia.
AB  - BACKGROUND: People with dementia encounter problems in eating and these have been
      reported in various studies. Many of these studies focus on individual
      difficulties and neglect the social, environmental and cultural aspects of meals
      and eating. Studies often centre on the problems of providing food instead of the
      experience of those receiving food. Less is known of the perspectives of family
      carers and residential or domiciliary care staff than of nurses' perceptions.
      Only recently are the perspectives of family carers and people with dementia
      joining nurses' discussions. AIM: The present paper considers feeding and eating
      in the context of enhancing support of life for people with dementia. Drawing on
      a range of literature, it highlights themes that are well developed and aims to
      identify areas of little knowledge and potential investigation. CONCLUSIONS: In
      the United Kingdom, the areas of feeding and eating are likely to assume greater
      importance in attempts to promote rehabilitation, in moves to offer training to
      unqualified staff and in enhanced vigilance of the experience of people with
      dementia. Their problems with respect to food and its consumption need to be
      interrogated and informed by interventions that are ethical, socially inclusive
      and acknowledge the importance of food to well-being.

PMID- 12519276
TI  - Practical nurses in elder care and changes in Finnish society - a biographical
      study.
AB  - BACKGROUND: Substantial changes in the socio-economic circumstances in Finnish
      society over the past century have resulted in major changes in the case of older
      people, and in the status of nursing staff who care for them. AIM: The purpose of
      this study was to describe and analyse the work of practical nurses in elder care
      through the experiences and life cycles of two practical nurses with a long
      working experience. METHODS: The data consisted of oral biographical narratives
      produced by the two nurses in repeated interviews. The data were analysed using
      inductive content analysis. FINDINGS: The following chronological stages and
      periods of the work of the informants emerged as the core themes of elder care:
      (1) Collective institutionalized care in the 1950s-1970s: The lowest caste in
      training, obedient subordinates, undemanding service and routine work; (2)
      Elderly orientated institutionalized care in the 1980s and 1990s: From
      subordination to co-operation as an experienced nurse, recognizing the specific
      qualities of the elderly; (3) Prospects of elder care from the 1990s onwards:
      Returning to custodial care? CONCLUSIONS: The themes are related to the more
      general changes that have taken place in Finnish society and health care. The
      future prospects of practical nurses seem challenging because the principles of
      social work and health care in Finnish society have shifted from
      institutionalization towards community care. As a consequence, practical nurses
      are required to have higher qualifications.

PMID- 12519277
TI  - Werna Naloo -'We Us Together': the birth of a midwifery education consortium.
AB  - AIM: The metaphor of a journey will be used to describe the process covering 2
      years of development of a Bachelor of Midwifery curriculum shared between a
      consortium of three universities in Victoria, Australia. BACKGROUND: The
      landscape or background against which this journey took place is described,
      providing a context for understanding the political and pragmatic steps necessary
      to achieve common vision and processes. This journey has necessitated a
      convergence of our thinking about what constitutes the living theory and
      philosophy of the new midwifery in the Australian context, and how this fits with
      international trends. PROCESS: The journey took midwife academics from one
      paradigm to another, forging partnerships between universities to develop an
      innovative undergraduate midwifery curriculum that shares academic expertise and
      resources. Consultation between a multitude of competing interests and voices
      became one of our biggest challenges, but this process itself has helped to
      change the very landscape in which we travel. In the end, we had to examine our
      baggage, and much that was excess had to be abandoned. In particular, our
      emphasis on language and the politics of the midwifery partnership with women
      became the subject of much debate and contention, and reflects the competing
      philosophies developing in the midwifery profession. Despite this, there were
      many who suggested that we had left behind too much, and others who would have us
      pack even more. Compromises were inevitable if we were to proceed and set up the
      next stage of a journey that would open a new and challenging frontier to working
      with Australian childbearing women.

PMID- 12519278
TI  - A training programme for prevention of occupational exposure to bloodborne
      pathogens: impact on knowledge, behaviour and incidence of needle stick injuries
      among student nurses in Changsha, People's Republic of China.
AB  - BACKGROUND: Although the human immunodeficiency virus (HIV) epidemic in China is
      expanding rapidly, the principles of universal precautions (UP) are not widely
      disseminated in Chinese hospitals. Lack of training about occupational prevention
      of bloodborne pathogens (BBP) may place student nurses at risk when they are in
      clinical practice. AIM: To examine the impact of structured training on
      prevention of occupational exposure to BBP on knowledge, behaviour, and incidence
      of medical sharp injuries among student nurses in Changsha, China. METHODS: A
      quasi-experimental study evaluated changes in knowledge, self-reported UP
      behaviours, observed adherence to UP, and needle stick/sharp injuries during a 4
      month follow-up period. The study population consisted of 106 student nurses in
      two classes. One class served as the experimental group, while the other served
      as a control group. Students in the experimental group participated in a
      structured training intervention consisting of lectures and demonstrations.
      RESULTS: At 4 months, the group that received the BBP training scored
      significantly higher than the standard education group on both knowledge (P <
      0.001) and behaviour (P = 0.002). Although students in the experimental group
      were not observed to practise UP significantly more frequently than those in the
      control group, they were less likely to experience needle stick/sharp injuries
      (OR = 0.29; 95% CI 0.11, 0.74; P = 0.004). CONCLUSION: Structured training in
      prevention of occupational exposure to BBP improved knowledge and behaviour and
      reduced the number of needle stick/sharp injuries among Chinese student nurses,
      compared with students who did not receive the training. Training in the
      techniques of UP could play a role in reducing the risk for occupational exposure
      to BBP among Chinese future nurses. In view of the accelerating HIV epidemic,
      implementation and evaluation of such training programmes are urgently needed.

PMID- 12519279
TI  - Creativity: a refinement of the concept for nursing practice.
AB  - AIMS: This paper seeks to remove some of the ambiguity surrounding the conceptual
      meaning of creativity using techniques of concept refinement to advance the
      concept. BACKGROUND: Creativity is an essential component of nursing practice
      that occurs daily in nurse's interactions with clients, families and other
      nurses. Failure to acknowledge and encourage creativity in beginning nurses may
      hinder future development and innovations in nursing practice and in nursing
      science. In order to promote the development of creativity it is first necessary
      to clarify and refine the concept as it applies to nursing. DESIGN/METHODS: A
      comprehensive review of a variety of computer and online databases resulted in
      thousands of articles on creativity between the years 1966 and 1999. The final
      sample (n = 48) was obtained using both stratified random and purposive sampling
      techniques. A content analysis of the literature was conducted using methods
      identified by Morse and illustrated in the work of Hupcey et al. Having
      determined the concept to be partially mature, the concept was advanced using
      techniques of concept refinement. FINDINGS: Content analysis of the literature
      yielded three differing definitions for creativity: revelation, birth and
      reincarnation. Creativity occurs in the presence of intrinsic motivation and a
      nurturing environment. While value is often used to identify whether a product is
      creative, the value of the product cannot determine whether the process has
      occurred. The product produced determines evidence of the process of creativity.
      LIMITATIONS: Limitations of this investigation are the use of secondary sources
      and the relatively small sample size (n = 48). CONCLUSIONS: Refinement of the
      concept of creativity indicates that it is a process that may be developed and
      influenced by the environment and is recognized by the product produced. Further
      investigation is needed to explore methods and techniques for developing
      creativity in nursing.

PMID- 12519283
TI  - Ageism: what's in a word!

PMID- 12519284
TI  - Accommodative speech and terms of endearment: elements of a language mode often
      experienced by older adults.
AB  - AIM: To discuss the use of patronizing patterns of speech and modified forms of
      address in conversations between nurses and other health workers, and older
      people. RATIONALE: The impetus for this paper was the publication of the National
      Service Framework for Older People, which draws attention to the prevalence of
      age discrimination and the need to provide individualized care. APPROACH: The
      literature between 1990 and 2001 was reviewed in a systematic way. Certain key,
      older texts were also identified. Twenty-four publications were found, which
      examine the ways in which nurses and other health workers modify their speech
      when conversing with older people, discuss what older people think about this
      practice, or otherwise contribute to this issue. RESULTS: The paper uses speech
      accommodation theory to explain how the language addressed to older people is
      sometimes modified. The practice of over-accommodation is also described. This
      happens when older people are addressed in a simplified vocabulary with a high
      pitched tone of voice and slow speech. The extent of over-accommodation is
      discussed, and its impact on older people is considered in terms of fostered
      dependence and lowered self-esteem. CONCLUSION: The findings of the review in the
      context of current policy related to older people and implications for nursing
      education are discussed.

PMID- 12519285
TI  - Development and testing of the theory of collaborative decision-making in nursing
      practice for triads.
AB  - BACKGROUND: Although nurses depend heavily on informal family caregivers to
      provide care to clients and to be involved in care planning and decision-making,
      no nursing theories that include the client, the caregiver, and the nurse were
      available to guide collaborative care planning and decision-making. AIM: The
      purpose of this paper is to describe the construction and initial testing of the
      theory of collaborative decision-making in nursing practice for a triad. The
      theory represents an extension of Kim's theory of collaborative decision-making
      in nursing practice. Kim's theory was developed to describe and explain
      collaborative decision-making in a dyad (client and nurse). The inclusion of a
      third person (family caregiver) in the theory required the addition of concepts
      about the caregiver, coalition formation, and nurse and caregiver outcomes. The
      expansion of Kim's dyadic theory to a triadic theory was achieved by means of a
      modified version of the theory derivation process described by Walker and Avant.
      CONCLUSIONS: The theory of collaborative decision-making in nursing practice for
      a triad can be used to guide further research and clinical practice. The theory
      provides a framework for researchers who are interested in studying the effects
      of collaboration regarding decision-making among nurses, family caregivers, and
      clients. The initial testing of the new theory in home health care nursing
      revealed variety in the nature of the client-caregiver-nurse relationships, the
      many processes used by the nurses in proceeding with the home visits, a multitude
      of decisions considered and different collaborative, noncollaborative, and
      coalition-forming interactions. The limited evidence of the empirical adequacy of
      the theory precludes development of definitive guidelines for clinical practice
      at this time. More studies are required before clinical practice guidelines can
      be developed.

PMID- 12519286
TI  - Two-year follow-up of a randomized controlled trial of a clinical nurse
      specialist intervention, inpatient, and day patient team care in rheumatoid
      arthritis.
AB  - AIM: To compare the long-term effectiveness of care delivered by a clinical nurse
      specialist (CNS) with inpatient team care and day patient team care in patients
      with rheumatoid arthritis and increasing functional limitations. Background. The
      role of CNSs in the management of patients with rheumatoid arthritis (RA) is
      evolving, and their effectiveness in comparison with care provided by a
      rheumatologist alone has been established. However, long-term controlled studies
      showing how the effectiveness of CNSs compares with that of other forms of co
      ordinated care, such as multidisciplinary team care, are lacking. METHODS: Two
      hundred and ten patients rheumatoid arthritis patients were randomized to care
      delivered by a CNS in a rheumatology outpatient clinic (12 weeks), inpatient team
      care (2 weeks) and day patient team care (3 weeks). Clinical assessments recorded
      on study entry, weeks 12, 26, 52, 78 and 104 comprised the health assessment
      questionnaire (HAQ) and MacMaster Toronto Arthritis (MACTAR) patient preference
      interview as primary outcome measures. Grip strength, walk test, RAND-36,
      Rheumatoid Arthritis Quality of Life questionnaire and disease activity score
      (DAS) were applied as secondary outcome measures. RESULTS: No significant
      differences in medical treatment, use of services of other health professionals,
      introduction of adaptive equipment or number of hospitalizations were observed
      between the three treatment groups during 2 year follow-up, except that visits to
      nurse specialists were more frequent and home help was less frequent in the CNS
      group. A comparison of clinical outcomes among the three groups and a comparison
      between the nurse specialist and inpatient and day patient care groups together
      did not show any significant differences. Within all three groups functional
      status, quality of life and disease activity improved significantly (P < 0.05).
      In general, the results obtained after 12 weeks remained stable until 104 weeks
      after the start of the study. CONCLUSION: Care provided by a CNS in an outpatient
      rheumatology clinic has a similar long-term clinical outcome to inpatient and day
      patient team care in patients with rheumatoid arthritis. A CNS intervention
      appears to be an effective innovation in the care for patients with rheumatoid
      arthritis.

PMID- 12519287
TI  - Living on dialysis: concerns of clients in a renal setting.
AB  - Background. This article reports a study that sought to understand the experience
      of a group of Caucasian men with end stage renal failure managing their own
      haemodialysis therapy in their homes. Methodology. The study used a critical
      interpretive methodology. The renal setting was critically viewed as a
      specialized health care context constituted by several interrelated discourses.
      Although established by the dominant professional discourse, it also includes a
      number of others, in particular an obscure client discourse that is a response to
      the dominant discourse. Methods. Initially participants' own interpretations of
      their individual experiences were outlined. These were then collectively
      reinterpreted by contextualizing them in terms of the critical view of the renal
      setting, in order to discern their own views as renal clients that were obscured
      by the language and ideas of the dominant discourse with which they had been
      enculturated. Findings. From an analysis of the set of accounts derived from
      interviews with six participants, four concerns of the renal client discourse
      were identified. Together these model their shared perspective, which underlies
      each of their individual accounts of their experience of illness and therapy.
      These concerns were: (1) suffering from continuing symptoms of end stage renal
      failure and dialysis; (2) limitations resulting from negotiating dialysis into
      their lifestyle; (3) ongoingness and uncertainty of life on dialysis; and (4)
      altered relationship between autonomy and dependence inherent in living on
      dialysis. Conclusion. One specific implication of this study is that the
      distinctive potential of the nursing role in renal settings lies beyond the
      performance of a range of technical tasks, in addressing the experience of people
      living on dialysis, described here as the concerns of the renal client discourse.

PMID- 12519288
TI  - Nurses' perceptions of critical incidents.
AB  - AIMS OF THE STUDY: To determine: (1) the types of clinical events nurses
      perceived as 'critical'; and (2) whether nurses' experiences of critical
      incidents were associated with any demographic variables such as qualifications
      and current area of work. BACKGROUND: A review of the literature revealed little
      research has investigated in detail which clinical events nurses perceived as
      'critical', apart from two North American studies. Exploratory research of
      Australian nurses was undertaken to confirm and contrast their understandings and
      views with those of other work specialties and North American findings.
      DESIGN/METHODS: Two hundred and twenty-seven full-time registered nurses at a
      metropolitan medical centre responded to a survey questionnaire designed for the
      study based on findings of earlier studies regarding critical incidents. RESULTS:
      Respondents viewed the sexual abuse of a child and death of a child as the most
      critical of events listed on the questionnaire and an emergency situation as the
      most frequent and stressful incident in the previous year. Factor analysis
      indicated the existence of three types of critical incident represented by Grief,
      Emergency, and Risk Scales. Events on the Grief scale were most stressful for
      respondents. Although several significant relationships were found for
      demographics with the Grief and Risk Scales, findings were considered tentative
      because of disproportionate representation on many of the demographics.
      CONCLUSION: Further research is necessary to substantiate the findings of the
      study. However, the identification of the scales provided a concise way of
      conceptualizing the essential elements of critical incidents.

PMID- 12519289
TI  - Exploring childhood immunization uptake with First Nations mothers in north
      western Ontario, Canada.
AB  - BACKGROUND: Childhood immunization is an important component of preventive health
      care for young children. Successful control of vaccine-preventable diseases
      depends on high levels of immunization coverage. Immunization statistics show
      that on-reserve First Nations (Native Indian) children have lower vaccination
      coverage than children in the general Canadian population. There has been little
      research, however, conducted with First Nations populations on this topic. AIM OF
      THE STUDY: This study explored First Nations parents' beliefs about childhood
      immunizations and examined factors influencing immunization uptake. METHODS: This
      study used a qualitative descriptive design to explore the issue of childhood
      immunization uptake. Twenty-eight mothers from two First Nations communities in
      north-western Ontario, Canada, were interviewed about their perceptions of
      childhood immunizations and vaccine-preventable diseases. The interviews were
      transcribed and content analysis was used to examine the data. FINDINGS: Data
      analysis revealed the following six themes: (1) the fear of disease; (2) the
      efficacy of immunizations; (3) the immunization experience; (4) the consequences
      of immunization; (5) interactions with health professionals; and (6) barriers to
      immunizations. Participants were motivated to seek immunizations for their
      children by a fear of vaccine preventable diseases. A small proportion of
      mothers, however, questioned the effectiveness of vaccines in preventing disease.
      Traumatic immunization experiences, vaccine side-effects and sequelae, negative
      interactions with health professionals, and barriers such as time constraints and
      childhood illnesses all served as deterrents to immunization. CONCLUSIONS: The
      research outcomes highlight the varied beliefs of First Nations parents about
      childhood immunizations and the numerous factors that both positively and
      negatively influence immunization uptake. Further research is needed to explore
      the issue of childhood immunizations in First Nations communities and to
      determine strategies to improve uptake.

PMID- 12519290
TI  - Development and testing of a Faces Scale for the assessment of anxiety in
      critically ill patients.
AB  - BACKGROUND: Many patients experience anxiety during treatment in an intensive
      care unit, but intensive care patients are often not able to respond to existing
      validated measures of anxiety such as the Brief Symptom Inventory. We have
      developed a new single item Faces Anxiety Scale made up of drawings of five
      faces. AIMS: The aims of this study were to: (i) assess the ability of intensive
      care patients to respond to the Faces Anxiety Scale; and (ii) investigate whether
      the scale yields ordinal and interval data. ETHICS: The project was approved by
      two Human Research Ethics Committees. Patients were included in the study if they
      gave informed consent. INSTRUMENTS AND METHODS: (i) Intensive care patients (n =
      40) were asked to respond to the Faces Anxiety Scale, the anxiety subscale of the
      Brief Symptom Inventory, and a numerical analogue anxiety scale; and (ii)
      Hospital and University staff and students (n = 75) were asked to place the five
      faces in rank order. A further 100 staff members and students were asked to place
      each face at a point on a 60-cm triangular wedge according to the level of
      anxiety they thought the face showed. RESULTS: The Faces Anxiety Scale elicited
      more responses from intensive care patients than the numerical analogue anxiety
      scale the or anxiety subscale of the Brief Symptom Inventory (36 vs. 25 vs. 17,
      respectively, P < 0.0001). In the testing of the order of the scale items, 93% of
      respondents independently placed the scale items in the order of least to most
      anxiety as intended in the design of the scale. In the testing for equality of
      intervals respondents placed the faces relatively equidistant, with no overlap of
      95% confidence intervals around the mean distances. CONCLUSION: The Faces Anxiety
      Scale has minimal subject burden, elicits self report from intensive care
      patients more often than other simple scales, and has evidence of the interval
      scale properties of rank order and equality between the points on the scale.

PMID- 12519291
TI  - Establishing methodological rigour in international qualitative nursing research:
      a case study from Ghana.
AB  - BACKGROUND: Attention to rigour, from the identification of the problem to the
      dissemination of the findings, is essential in all qualitative research. In this
      paper, research carried out in Ghana in 1999 is used to highlight methodological
      issues in relation to rigour in international qualitative nursing research. AIM:
      The purpose of this paper is to review the literature in relation to rigour in
      qualitative research, highlight the methodological decisions enhancing rigour
      during this research project, and describe the criteria used to assess rigour
      during the research process. DESIGN: A participatory action research design was
      used to explore the cultural, social, economic, and political factors that
      influenced Ghanaian women's vulnerability to HIV infection. Collaboration with
      participants and partnerships with key professionals were integral to the design
      of the study. FINDINGS: Participatory action research provided a flexible,
      socially, and culturally adaptable framework to guide this international research
      project. Prior to the initiation of international research it was essential to
      establish the relevance and feasibility of the proposed project. This
      international research project posed additional methodological challenges to the
      establishment of rigour. Patience, flexibility and sensitivity were required of
      the researcher to overcome these challenges. CONCLUSION: Collaboration with
      participants and with culture-specific 'experts' may be key to culturally
      competent scholarship, particularly in unfamiliar settings.

PMID- 12519292
TI  - Personal improvement project in nursing education: learning methods and tools for
      continuous quality improvement in nursing practice.
AB  - BACKGROUND: All health care providers, including nurses, need to learn how to
      improve the care they give. Continuous quality improvement (CQI) is a theory and
      method used in health care to guide improvement. The question is how best to
      teach it, particularly to nursing students. It was conjectured that a systematic
      approach to improve study habits and lifestyle would increase nursing students'
      awareness of how they handled their studies and, at the same time, became
      acquainted with improvement knowledge methodology. Using the starting point that
      'quality is personal', students worked on personal change and improvement. The
      purpose was to learn methods and tools for improvement in their personal life and
      enable them to transfer and use this knowledge in their professional work. AIMS:
      To describe the use of a personal improvement project (PIP) by nursing students
      and the resulting increased knowledge, skills, and enthusiasm to continue working
      with CQI. METHODS: Forty-four nursing students worked on a PIP, which they felt
      was important, and presented their projects to fellow students. The students
      answered a questionnaire, and their presentations documented the results of their
      work. RESULTS: All 44 students followed the instructions in a workbook describing
      PIPs over an 8-week period and answered a questionnaire. Forty-five per cent felt
      they had made an improvement in their study habits or lifestyle. Eighty-nine per
      cent reported that this project helped them to start learning CQI, and 75%
      reported that they could see the benefit of this kind of knowledge in their
      future clinical practice. CONCLUSIONS: Personal improvement projects seem to be
      an effective way of introducing CQI knowledge to nursing students. Even those who
      did not succeed in achieving personal improvement felt they had a positive
      learning outcome from the project.

PMID- 12519293
TI  - A study to evaluate the pain knowledge of two sub-populations of final year
      nursing students: Australia and Philippines.
AB  - BACKGROUND: Pain management is an essential and important aspect of nursing care.
      Deficits in pain knowledge and attitudes continue to be reported despite a growth
      of educational programmes. A lack of basic knowledge of pain at an undergraduate
      level may limit nurses from effectively developing their knowledge after
      graduation. AIM OF THE STUDY: To assess the type and level of knowledge of basic
      aspects of pain mechanisms and treatment principles in complete classes of final
      year nurses, at three nursing schools. METHOD: Data were collected in 1999, from
      150 students (81 Australian and 69 Philippine) via a 23-item pain knowledge test
      questionnaire, previously used to assess undergraduate health professionals
      including nurses. RESULTS: The mean score of concordant answers for all students
      was 38.6%, scores ranged from 0% to 70%, 95% Confidence Interval of the mean was
      36-41%. There were few significant differences between the groups for individual
      questions and no significant difference in overall mean scores. Common questions
      answered poorly included those related to complex regional pain syndrome,
      pharmacology and central sensitization. Most students perceived their
      undergraduate pain education to be minimal. Thirty-six per cent of Australian
      students compared with 50% Filipino students perceived their pain knowledge was
      adequate for their clinical needs. Additionally, most students believed that
      graduating doctors should be able to answer the test questions correctly.
      CONCLUSION: The results demonstrate consistently low levels of knowledge and also
      knowledge gaps about basic pain mechanisms, terms and treatment amongst these
      three final year nursing classes. Such information is useful to define levels of
      basic knowledge about this topic, and can be explored further as to whether some
      or all of these facts are deemed necessary for inclusion in nursing curriculum by
      reference to documents such as the International Association for the Study of
      Pain curriculum.

PMID- 12519294
TI  - Response to: 'The writing experiences of a group of student nurses: a
      phenomenological study' by D. Whitehead (2002) Journal of advanced nursing 38(5),
      498-506.

PMID- 12519295
TI  - Natural killer T cells are targets for human immunodeficiency virus infection.

PMID- 12519296
TI  - CD1d-restricted natural killer T cells are potent targets for human
      immunodeficiency virus infection.
AB  - Invariant human natural killer T cells (NKT) express a restricted T-cell receptor
      (TCR) Valpha24Vbeta11 repertoire. These cells share both phenotypic and
      functional similarities between NK and T cells. Given the emerging role of NKT
      cells as critical cells in bridging the gap between innate and adaptive immunity,
      we examined their susceptibility to productive human immunodeficiency virus (HIV)
      infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three
      human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these
      Valpha24+ Vbeta11+ clones indicated that they were predominately positive for
      CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones
      expressed significantly more surface CCR5 molecules/cell and lower CXCR4
      molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear
      cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT
      clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary
      isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay
      and intracellular staining of HIV proteins. The amount of p24 production was
      dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31
      were also susceptible to HIV IIIB infection. The virions produced by these clones
      were able to productively infect PHA-stimulated PBMCs with the same kinetics as
      for primary infection of CD4+ blast. Collectively, this data demonstrates that
      NKT cells can be a target for productive HIV infection but with a lag in the time
      to peak p24 production.

PMID- 12519297
TI  - Distribution of Toll-like receptor 1 and Toll-like receptor 2 in human lymphoid
      tissue.
AB  - To determine how distinct receptors of the immune system can contribute to innate
      immunity, we investigated the pattern of Toll-like receptor 1 (TLR1) and TLR2
      expression in human lymphoid tissue. We found that TLR1 and TLR2 were co
      expressed on cells of the innate immune system, including macrophages and
      dendritic cells. In addition, TLR1 and TLR2 were expressed in mucosa-associated
      lymphoid tissue on tonsillar crypt epithelium. Of the lymphoid tissue examined,
      spleen expressed the highest levels of TLR2. Although TLR1- and TLR2-positive
      cells were in close proximity to T lymphocytes in vivo, lymphocytes themselves
      were devoid of TLR1 and TLR2 expression. The co-expression of TLR1 and TLR2 on
      myeloid cells in lymphoid tissue provides the host with the ability to respond to
      a variety of microbial ligands at sites conducive to the generation of an immune
      response.

PMID- 12519298
TI  - Identification of a new cluster of T-cell receptor delta recombining elements.
AB  - Within the human T-cell receptor delta (TCRD) gene we have identified a new
      cluster of seven delta recombining elements (deltaRec2.1-2.7), located 2.6-5.2
      kilobases downstream of the Vdelta2 gene segment. The deltaRec2 elements are
      isolated recombining signal sequences (RSS), which were shown to rearrange with
      the Ddelta3 and Jdelta1 segments of the TCRD gene as well as with the psiJalpha
      of the TCRA gene. Rearrangements involving the deltaRec2 elements were found in
      all peripheral blood (PB) samples from 10 healthy individuals, although their
      frequency was about 100-fold lower than that of classical deltaRec
      rearrangements. The total frequency of deltaRec2 rearrangements was lower in PB T
      lymphocytes, as compared with thymocytes, suggesting that they are deleted during
      T-cell development. The decrease of the frequency of the deltaRec2-Ddelta3
      rearrangements was most prominent: 11 times lower in PB T lymphocytes than in
      thymocytes. Since the deltaRec2-Jdelta1 rearrangements contained the Ddelta3
      segment in the junctional region, we assume that they are derived from the
      deltaRec2-Ddelta3 rearrangements. In contrast, the majority of deltaRec2
      psiJalpha rearrangements did not contain the Ddelta3 segment, indicating that
      they are single step rearrangements. The deltaRec2-Jdelta1 and deltaRec2
      psiJalpha rearrangements seem to be T-lineage specific, but the deltaRec2-Ddelta3
      rearrangements were also found at very low frequencies in B lymphocytes and
      natural killer cells. Our results suggest that deltaRec2 rearrangements are
      transient steps in the recombinatorial process of the TCRAD locus and are
      probably deleted by subsequent Valpha-Jalpha rearrangements. We hypothesize, that
      in a similar manner to the classical deltaRec rearrangements, the deltaRec2
      rearrangements might also contribute to T-cell differentiation towards the TCR
      alphabeta lineage.

PMID- 12519299
TI  - In vivo maintenance of T-lymphocyte unresponsiveness induced by thymic medullary
      epithelium requires antigen presentation by radioresistant cells.
AB  - The T-cell repertoire developing in the thymus is rid of autospecific cells by
      the process of thymic negative selection. Recognition of major histocompatibility
      complex (MHC)/self-peptide complexes expressed by thymic antigen-presenting cells
      (APC) of bone marrow origin leads to induction of apoptotic death of autospecific
      thymocytes. Induction of tolerance to self-antigens not presented by thymic APC
      is mediated by medullary thymic epithelial cells (mTEC) which express a very wide
      range of proteins, e.g. inducible and tissue-specific proteins. The main type of
      tolerance induced by mTEC is non-deletional and the issue of how it is maintained
      outside the thymus is therefore of crucial interest. We have previously shown
      that the non-T-cell receptor (TCR) -transgenic T-cell repertoire developing in
      conditions in which tolerance to self-MHC/peptide ligands is exclusively induced
      by mTEC is tolerant to syngeneic targets in vivo but lyses such targets in vitro.
      Here we report that this non-deletional in vivo self-tolerance is not due to
      active tolerance assured by known naturally occurring regulatory or immune
      modulating T lymphocytes. Importantly, we show that in vivo maintenance of this
      therefore probably anergic state requires continued interaction of autospecific T
      cells with self-MHC/peptide ligands expressed by radioresistant cells while APC
      are incapable of maintaining the tolerant state. Therefore, maintenance of non
      deletional T-lymphocyte tolerance to the wide range of self-antigens expressed by
      mTEC depends on continued interaction with radioresistant cells that very
      probably express a much more limited repertoire of antigens. Our data may
      therefore have important consequences for tolerance to tissue-specific and
      inducible self-antigens.

PMID- 12519301
TI  - Tumour necrosis factor-alpha but not lipopolysaccharide enhances preference of
      murine dendritic cells for Th2 differentiation.
AB  - Using murine spleen-derived dendritic cells (DC) and DO11.10 T cells specific for
      ovalbumin (OVA), the influences of maturational condition and antigen dose on the
      capability of DC to induce helper T-cell (Th) differentiation were analysed.
      Immature DC (iDC) with high- or low-dose OVA(323-339) predominantly induced Th1
      or Th2 responses in DO11.10 T cells, respectively. DC matured by tumour necrosis
      factor-alpha (TNF/DC) induced a significantly higher Th2 response in the presence
      of low-dose OVA(323-339) than iDC and DC matured by lipopolysaccharide (LPS)
      (LPS/DC). In the presence of high-dose OVA(323-339), LPS/DC induced significantly
      lower levels of Th1 response than iDC. Under these conditions no difference in
      the Th1 response was noted between TNF/DC and iDC. The enhanced capability of
      TNF/DC with a low-dose antigen for Th2 polarization and the decreased preference
      of LPS/DC with a high-dose antigen to Th1 polarization were not related to the
      amount of IL-12 produced in these cultures. These results demonstrate for the
      first time that TNF/DC with a low-dose antigen are potent inducers of Th2
      differentiation.

PMID- 12519300
TI  - Form and pattern of MUC1 expression on T cells activated in vivo or in vitro
      suggests a function in T-cell migration.
AB  - MUC1 is a transmembrane mucin that is expressed on ductal epithelial cells and
      epithelial malignancies and has been proposed as a target antigen for
      immunotherapy. The expression of MUC1 has recently been reported on T and B
      cells. In this study we demonstrate that following activation in vivo or
      activation by different stimuli in vitro, human T cells expressed MUC1 at the
      cell surface. However, the level of expression in activated human T cells was
      significantly lower than that seen on normal epithelial cells or on breast cancer
      cells. In contrast, resting T cells did not bind MUC1-specific monoclonal
      antibodies (mAbs), nor was MUC1 mRNA detectable by reverse transcription
      polymerase chain reaction (RT-PCR) or Northern blot analysis in these cells. The
      profile of activated T-cell reactivity with different MUC1-specific antibodies
      suggested that the glycoform of MUC1 expressed by the activated T cells carried
      core 2-based O-glycans, as opposed to the core 1 structures that dominate in the
      cancer-associated mucin. Confocal microscopy revealed that MUC1 was uniformly
      distributed on the surface of activated T cells. However, when the cells were
      polarized in response to a migratory chemokine, MUC1 was found on the leading
      edge rather than on the uropod, where other large mucin-like molecules on T cells
      are trafficked. The concentration of MUC1 at the leading edge of polarized
      activated human T cells suggests that MUC1 could be involved in early
      interactions between T cells and endothelial cells at inflammatory sites.

PMID- 12519302
TI  - Tumour necrosis factor-alpha is a fundamental cytokine in autoimmune thyroid
      disease induced by thyroglobulin and lipopolysaccharide in interleukin-12 p40
      deficient C57BL/6 mice.
AB  - Experimental autoimmune thyroiditis (EAT) is inducible in mice by immunization
      with mouse thyroglobulin (mTg) together with adjuvant, either lipopolysaccharide
      (LPS) or complete Freund's adjuvant (CFA). The severity of the disease is
      dependent on the mouse strain and on the adjuvant used. We have previously shown
      that interleukin (IL)-12 deficient C57BL/6 mice immunized with mTg and CFA
      develop a significantly less severe thyroid infiltration in comparison to wild
      type C57 BL/6 mice. This result indicated a pivotal role for IL-12 in the
      development of thyroiditis induced with CFA and mTg. In the present study we
      demonstrate that IL-12 deficiency does not impair EAT induction when LPS is used
      as adjuvant. We also demonstrate that peritoneal exudate cells from IL-12
      deficient mice stimulated in vitro either with LPS or IL-18 secrete high levels
      of tumour necrosis factor (TNF). Together the results emphasize the difference
      between the use of CFA and LPS in the induction of EAT, the importance of TNF
      alpha for the pathogenesis of LPS-induced EAT, and also show the capacity of IL
      12-deficient mice to develop a competent response to LPS.

PMID- 12519303
TI  - Differential response of bovine monocyte-derived macrophages and dendritic cells
      to infection with Salmonella typhimurium in a low-dose model in vitro.
AB  - Exposing bovine dendritic cells (DC) and macrophages (MPhi) to Salmonella
      typhimurium at a ratio of 1 cell to 10 bacteria had a cytotoxic effect that was
      not evident with a ratio of 1000 cells to 1 bacterium. This lower dose was
      considered to mimic more closely the in vivo situation and a comparison was made
      with this model of the consequences of infection for MPhi and DC. DC infected
      with S. typhimurium up-regulated cell surface expression of major
      histocompatibility class I (MHC-I), MHC-II, CD40, CD80 and CD86. In contrast,
      infected MPhi did not exhibit detectable changes in expression of cell surface
      molecules, except for a marginal increase in CD40. mRNA transcription for tumour
      necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and inducible nitric oxide
      synthase was up-regulated in both infected DC and infected MPhi, although mRNA
      transcription for granulocyte-macrophage colony-stimulating factor and IL-12p40
      was up-regulated only in infected DC and for IL-10 was only in infected MPhi.
      Infected DC had an increased ability to stimulate both allogeneic and antigen
      specific T-cell responses compared to non-infected controls. In contrast,
      infected MPhi showed an increased ability to induce allogeneic responses but this
      was less than seen for DC and no enhancement of ability to induce antigen
      specific T cell responses was seen. Thus, in a low-dose infection model that does
      not result in the cytotoxicity of a substantial percentage of antigen presenting
      cells, bovine MPhi and DC respond differently to infection with S. typhimurium
      and this could have important implications for the development of the immune
      response.

PMID- 12519304
TI  - Activation of macrophages and interference with CD4+ T-cell stimulation by
      Mycobacterium avium subspecies paratuberculosis and Mycobacterium avium
      subspecies avium.
AB  - Mycobacterium avium subspecies paratuberculosis (M. ptb) and M. avium subspecies
      avium (M. avium) are closely related but exhibit significant differences in their
      interaction with the host immune system. The macrophage line, J774, was infected
      with M. ptb and M. avium and analysed for cytokine production and stimulatory
      capacity towards antigen-specific CD4+ T cells. Under all conditions J774 cells
      were activated to produce proinflammatory cytokines. No influence on the
      expression of major histocompatibility complex (MHC) class II, intracellular
      adhesion molecule-1 (ICAM-1), B7.1, B7.2 or CD40 was found. However, the antigen
      specific stimulatory capacity of J774 cells for a CD4+ T-cell line was
      significantly inhibited after infection with M. ptb, but not with M. avium. When
      a T-cell hybridoma expressing a T-cell receptor identical to that of the T-cell
      line was used, this inhibition was not observed, suggesting that costimulation
      which is essential for the CD4+ T-cell line is influenced by the pathogenic
      bacterium M. ptb.

PMID- 12519305
TI  - Mycobacteria, an environmental enhancer of lupus nephritis in a mouse model of
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease
      characterized by the production of antibodies directed against self antigens.
      Immune complex glomerulonephritis (GN) is one of the most serious complications
      of this disorder and can lead to potentially fatal renal failure. The aetiology
      of SLE is complex and multifactorial, characterized by interacting environmental
      and genetic factors. Here we examine the nature of the renal pathology in
      mycobacteria-treated non-obese diabetic (NOD) mice, in order to assess its
      suitability as a model for studying the aetiopathogenesis of, and possible
      treatment options for, lupus nephritis (LN) in humans. Both global and segmental
      proliferative lesions, characterized by increased mesangial matrix and
      cellularity, were demonstrated on light microscopy, and lesions varied in
      severity from very mild mesangiopathic GN through to obliteration of capillary
      lumina and glomerular sclerosis. Mixed isotype immune complexes (IC) consisting
      of immunoglobulin G (IgG), IgM, IgA and complement C3c were detected using direct
      immunofluorescence. They were deposited in multiple sites within the glomeruli,
      as confirmed by electron microscopy. The GN seen in mycobacteria-treated NOD mice
      therefore strongly resembles the pathology seen in human LN, including
      mesangiopathic, mesangiocapillary and membranous subclasses of LN. The
      development of spontaneous mixed isotype IC in the glomeruli of some senescent
      NOD mice suggests that mycobacterial exposure is accelerating, rather than
      inducing, the development of GN in this model.

PMID- 12519307
TI  - Functional and phenotypic studies of two variants of a human mast cell line with
      a distinct set of mutations in the c-kit proto-oncogene.
AB  - The human mast cell line (HMC)-1 cell line is growth-factor independent because
      of a constitutive activity of the receptor tyrosine kinase Kit. Such deregulated
      Kit activity has also been suggested causative in gastrointestinal stromal
      tumours (GISTs) and mastocytosis. HMC-1 is the only established continuously
      growing human mast cell line and has therefore been widely employed for in vitro
      studies of human mast cell biology. In this paper we describe two sublines of HMC
      1, named HMC-1(560 ) and HMC-1(560,816 ), with different phenotypes and
      designated by the locations of specific mutations in the c-kit proto-oncogene.
      Activating mutations in the Kit receptor were characterized using the
      pyrosequencing trade mark method. Both sublines have a heterozygous T to G
      mutation at codon 560 in the juxtamembrane region of the c-kit gene causing an
      amino acid substitution of Gly-560 for Val. In contrast, only HMC-1(560,816)
      cells have the c-kitV816 mutation found in mast cell neoplasms causing an Asp-
      >Val substitution in the intracellular kinase domain. Kit was constitutively
      phosphorylated on tyrosine residues and associated with phosphatidylinositol 3'
      kinase (PI 3-kinase) in both variants of HMC-1, but this did not lead to a
      constitutive phosphorylation of Akt or extracellular regulated protein kinase
      (ERK), which are signalling molecules normally activated by the interaction of
      stem cell factor (SCF) with Kit. The documentation and characterization of two
      sublines of HMC-1 cells provides both information on the biological consequences
      of mutations in Kit and recognition of the availability of what in reality are
      two distinct cultured human mast cell lines.

PMID- 12519306
TI  - Mycobacterium bovis bacillus Calmette-Guerin-infected dendritic cells potently
      activate autologous T cells via a B7 and interleukin-12-dependent mechanism.
AB  - Mycobacteria are potent adjuvants, can survive intracellularly and have been
      safely used for many years as vaccines against tuberculosis and leprosy. They are
      thus important potential vectors for recombinant vaccines. Many of their adjuvant
      properties are mediated following phagocytosis by dendritic cells (DC), which are
      in turn critical for priming naive T cells. Although the maturation of DC in
      response to mycobacteria, such as Mycobacterium bovis bacillus Calmette-Guerin
      (BCG), is well described the subsequent responses of autologous T cells to
      mycobacterium-infected DC remains uncharacterized. In our experiments DC infected
      with BCG expressed more co-stimulatory molecules than tumour-necrosis factor
      alpha (TNF-alpha) -treated DC and stimulated more potent mixed leucocyte
      reactions. When autologous T cells were co-cultured with BCG-exposed DC they
      became highly activated, as determined by display of CD25, CD54 and CD71 on both
      CD4+ and CD8+ cells. In contrast, the response of T cells to TNF-alpha-matured DC
      was significantly less. Cytokine production from T cells cultured with BCG
      exposed DC was enhanced with elevated secretion of interleukin-2 (IL-2), IL-10
      and interferon-gamma (IFN-gamma) and was produced by both CD4+ and CD8+
      lymphocytes as determined by intracellular staining. In particular, IFN-gamma
      secretion was increased from 50 pg/ml to 25 000 pg/ml and IL-10 secretion
      increased from 20 pg/ml to 300 pg/ml in BCG-exposed DC co-cultures. Blocking
      antibodies to B7.1 and B7.2 or IL-12 significantly reduced the secretion of IFN
      gamma and reductions were also seen in the expression of CD25 and CD71 by CD4+
      cells. These data demonstrate that mycobacterially infected DC are particularly
      potent activators of autologous T cells compared to TNF-alpha-exposed DC and that
      the resultant T cells are functionally superior.

PMID- 12519308
TI  - gammadelta T cells contribute to the systemic immunoglobulin E response and local
      B-cell reactivity in allergic eosinophilic airway inflammation.
AB  - Allergic airway inflammation induced in mice is T-cell dependent and recruitment
      of eosinophils to airspaces requires both alphabeta and gammadelta T cells. From
      previous studies it is evident that alphabeta T cells are essential for the
      allergic T helper type 2 (Th2)-like response, while the mechanistic contribution
      of gammadelta T cells is still unclear. In this study, we have investigated the
      role of gammadelta T cells in allergic airway eosinophilia induced by ovalbumin
      hypersensitivity. By comparing the responsiveness to sensitizing allergen of wild
      type mice with that of T-cell receptor gammadelta knockout mice (TCRgammadelta
      KO) we demonstrated that mice lacking gammadelta T cells are defective in the
      systemic ovalbumin-specific immunoglobulin E (IgE) response. Furthermore, after
      aerosol challenge with allergen, gammadelta T-cell deficient mice exhibited a
      significantly decreased migration of B cells and natural killer cells to airways
      and reduced levels of allergen-specific IgG and IgA in bronchoalveolar lavage
      fluid. The role for B cells in the airway inflammation was indicated by the
      impaired ability of mice lacking functional B cells to evoke an eosinophilic
      response. The diminished eosinophilia in TCRgammadelta KO mice could not be
      explained by a defective Th2 activation since these mice displayed a normal IgG
      response in serum and an unaffected IG2b/IgG1 ratio in airways. Analysis of
      immunoregulatory cytokines in isolated lung tissue, thoracic lymph nodes and
      spleen further supported the notion that these mice are able to evoke a
      sufficient activation of T helper cells and that gammadelta T cells are not
      required for maintaining the Th2 profile. These results indicate that gammadelta
      T cells contribute to allergic airway inflammation by pathways separate from
      classical Th2 immune activation.

PMID- 12519309
TI  - Respiratory syncytial virus infection and virus-induced inflammation are modified
      by contaminants of indoor air.
AB  - The airway epithelium is the first cellular component of the lung to be
      encountered by the particles and pathogens present in inhaled air. In addition to
      its role as a physical barrier, the immunological activity of the airway
      epithelium is an essential part of the pulmonary immune system. This means that
      the symptoms of lung diseases that involve immunological mechanisms are
      frequently exacerbated by infection of the airway epithelium with respiratory
      viruses. The virus-induced enhancement of immunological activity in infected
      epithelial cells is well characterized. However, the effects that contaminants of
      inhaled air have upon the infectivity and replication of respiratory viruses and
      the inflammation they cause, are comparatively unknown. In this study, we have
      shown that pre-exposure of airway epithelial cells to bacterial
      lipopolysaccharides or a proteolytically active house dust mite allergen, is able
      to, respectively, inhibit or enhance the level of cellular infection with
      respiratory syncytial virus and similarly alter virus-induced expression of the
      inflammatory chemokine interleukin-8. These results suggest that respiratory
      syncytial virus infection and the inflammation caused by respiratory syncytial
      virus may be modified by the biologically active contaminants of indoor air.

PMID- 12519313
TI  - Type 2 diabetes and cognitive impairment.

PMID- 12519310
TI  - Apoptosis-inducing protein derived from hepatocyte selectively induces apoptosis
      in lymphocytes.
AB  - The liver is where lymphocytes undergo activation-induced cell death (AICD) at
      the resolution phase of an immune response, which is crucial for homeostasis of
      the immune system and prevention of autoimmunity. Exploring the machinery of AICD
      in the liver, we found that a primary culture supernatant of murine hepatocytes
      had an antiproliferative effect on antigen-stimulated T clone and T lymphoma
      cells. Biological study showed that the antiproliferation was due to induction of
      apoptosis in a caspase-dependent manner. The apoptosis-inducing potential was
      sensitive to trypsin, heat (> 70 degrees ) and acid (< pH 5) treatment but could
      not be neutralized by anti-tumour necrosis factor-alpha, anti-Fas ligand, or anti
      transforming growth factor-beta antibodies. Biochemical study of the isolated and
      purified apoptosis-inducing component from the supernatant showed that it was a
      protein with a molecular mass of about 68,000-70,000. It induced apoptotic change
      in murine T and B cells, and to a lesser degree, in human lymphoid cells, but not
      in macrophages. Biochemical and biological characteristics distinguish this
      protein from others that have been reported to induce apoptosis of lymphocytes.
      The identification of an apoptosis-inducing protein derived from murine
      hepatocytes, which selectively induces apoptosis in lymphocytes, suggests one
      possible mechanism for immune suppression in the liver.

PMID- 12519314
TI  - The role of the growth hormone-insulin-like growth factor axis in glucose
      homeostasis.
AB  - Homeostatic mechanisms normally maintain the plasma glucose concentration within
      narrow limits despite major fluctuations in supply and demand. There is
      increasing evidence that the growth hormone (GH)-insulin-like growth factor (IGF)
      axis may play an important role in glucose metabolism. GH has potent effects on
      intermediary metabolism, some of which antagonize the actions of insulin. In
      contrast, IGF-I has insulin-like actions, which are, in the case of glucose
      metabolism, opposite to those of GH. There is often deranged glucose metabolism
      in situations where GH is deficient or in excess. The clinical administration of
      GH or IGF-I results in altered glucose metabolism and changes in insulin
      resistance. Despite these observations, the precise role of GH and IGF-I and
      their interactions with insulin in controlling normal glucose homeostasis are
      unknown. In diabetes, GH secretion is abnormally increased as a result of reduced
      portal insulin resulting in impaired hepatic IGF-I generation. Evidence suggests
      that this may contribute to the development of diabetic microvascular
      complications. IGF-I 'replacement' in diabetes is under investigation and new
      methods of delivering IGF-I as a complex with IGFBP-3 offer exciting new
      prospects.

PMID- 12519315
TI  - Tissue factor pathway inhibitor (TFPI) release after heparin stimulation is
      increased in Type 1 diabetic patients with albuminuria.
AB  - AIMS: To study heparin-stimulated TFPI release in relation to complications in
      Type 1 diabetic patients. SUBJECTS AND METHODS: Nineteen uncomplicated Type 1
      diabetic patients (group I) were compared with 18 patients with retinopathy
      (group II), and nine patients with retinopathy and albuminuria (group III). Blood
      samples were taken before (basal) and till 30 min after 5000 IU of heparin i.v.
      (post-heparin). TFPI activity was measured chromogenically. Von Willebrand
      factor, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1
      (PAI-1) and thrombomodulin were also measured. RESULTS: Basal TFPI activity was
      higher in group III (121 +/- 10%) compared with group II (111 +/- 8%) or group I
      (110 +/- 13%) (P < 0.05), and strongly correlated with albuminuria (r = 0.66, P <
      0.05). At all time points after heparin administration, TFPI activity in group
      III was significantly higher than in group I. TFPI activity was also higher in
      group III than in group II 5-30 min post-heparin. The increase in post-heparin
      TFPI activity, measured as the incremental area under the curve, was higher in
      group III compared with group I (65 +/- 7 vs. 59 +/- 4; P < 0.05). Of the other
      parameters, only thrombomodulin was higher in group III (44 +/- 24 vs. 26 +/- 7
      (group II) and 28 +/- 9 ng/ml (group I); P < 0.01). CONCLUSIONS: We conclude that
      basal and post-heparin TFPI activity is increased in albuminuric patients. The
      increase in heparin-stimulated TFPI release in patients with albuminuria is
      higher than in patients with retinopathy or without complications. This could be
      the result of altered endothelial glycosaminoglycan characteristics.

PMID- 12519316
TI  - High incidence of Type 2 diabetes mellitus in South African Indians: a 10-year
      follow-up study.
AB  - AIMS: Previous cross-sectional studies have established that South African
      Indians have a high prevalence of Type 2 diabetes mellitus. A prospective
      community study was undertaken to determine the incidence of Type 2 diabetes and
      the risk factors associated with its development in a cohort of South African
      Indians who had been studied 10 years previously. METHODS: This is a report on
      563 subjects who participated both at baseline and at the 10-year follow-up
      study. In the baseline study, 2479 subjects (> 15 years) were studied; using 1985
      World Health Organization criteria for glucose tolerance based on 75 g oral
      glucose tolerance tests (OGTT), the crude prevalence of diabetes mellitus
      (Diabetes) was 9.8% and of impaired glucose tolerance (IGT) 5.8% (age and sex
      adjusted prevalence 13% and 6.9%, respectively). RESULTS: At the 10-year follow
      up study, 563 of the subjects who could be traced consented to a repeat OGTT; of
      these, 91 (16.2%) were classified as Diabetes and 41 (7.3%) as IGT. Of the
      subjects who did not have diabetes at baseline (n = 517), 49 (9.5%) progressed to
      diabetes (PTD) and 40 (7.7%) had IGT. The crude cumulative incidence of diabetes
      was 9.5% (rate of progression 0.95% per annum; incidence density 9.5/1000 person
      years) with an age and sex-adjusted cumulative incidence of 8.3% (rate of
      progression 0.95% per annum; incidence density 8.3/1000 person years).
      Examination of risk factors predictive of subsequent diabetes development was
      undertaken by analysis of baseline (year 0) variables in the 517 subjects who did
      not have diabetes at baseline. In multivariate analysis using a logistic
      regression model, the significant predictive risk factors for future diabetes
      included 2-h post load plasma glucose (2 PG) (P < 0.0001, odds ratio (OR) 1.7,
      95% confidence interval (CI) 1.4-2.1), body mass index (BMI) (P < 0.006, OR 1.1,
      95% CI 1.0-1.3) and obesity (P < 0.01, OR 4.6, 95% CI 1.4-14.7). CONCLUSIONS:
      This long-term study has shown that in South African Indians there is a high
      incidence of Type 2 diabetes, and in this population significant predictors
      include higher baseline blood glucose, BMI and obesity.

PMID- 12519317
TI  - Microalbuminuria is more frequent in South Asian than in European origin
      populations: a comparative study in Newcastle, UK.
AB  - AIMS: We aimed to compare levels of urinary albumin excretion and the prevalence
      of microalbuminuria in UK South Asians and Europeans. Microalbuminuria predicts
      cardiovascular disease in European origin populations, but evidence from the
      general population of South Asians is lacking. Coronary heart disease (CHD)
      mortality is 40-50% higher in UK South Asians compared with the whole population,
      for reasons that are incompletely understood. METHODS: Microalbuminuria was
      measured using the albumin-creatinine ratio in an age- and sex-stratified random
      sample of 1509 adults from European (n = 825), Indian (n = 259), Pakistani (n =
      305) and Bangladeshi (n = 120) ethnic groups. RESULTS: Levels of urinary albumin
      excretion were substantially higher in South Asians (geometric mean albumin
      creatinine ratio (95% confidence interval) 0.83 (0.75, 0.91)) than in Europeans
      (0.55 (0.51, 0.60)). Microalbuminuria was associated with older age, hypertension
      and diabetes, but independently of these risk factors urinary albumin excretion
      was higher in South Asians than Europeans. CONCLUSIONS: Urinary albumin excretion
      is higher and microalbuminuria more frequent in UK South Asians compared with the
      majority ethnic population. Microalbuminuria may be relevant to the causal
      pathways leading to the excess of cardiovascular mortality and possibly renal
      failure in UK South Asians.

PMID- 12519318
TI  - Heterogeneity of non-insulin-dependent diabetes expressed as variability in
      insulin sensitivity, beta-cell function and cardiovascular risk profile.
AB  - AIMS: The present study investigated the variability in insulin sensitivity and
      beta-cell function and their relationship to anti-glutamic acid decarboxylase
      (GAD) positivity and the metabolic syndrome in a group of patients with non
      insulin-dependent diabetes mellitus (NIDDM). METHODS: Fifty-four subjects aged
      59.5 +/- 6.1 (mean +/- SD) years with NIDDM for 7.9 +/- 3.9 years referred to
      hospital due to poor glycaemic control, were investigated. Insulin sensitivity
      was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as
      the glucose disposal rate relative to the insulin level obtained (GDRI), and also
      estimated with the homeostasis model assessment (HOMA-S). beta-cell function was
      measured by assaying the fasting and glucagon-stimulated C-peptide levels and
      with the HOMA-B. RESULTS: The insulin sensitivity varied 18-fold between subjects
      when estimated with the clamp and six-fold when estimated with HOMA-S, and was
      lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova).
      The beta-cell function varied four-fold when measured as stimulated C-peptide,
      and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide
      and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD
      subjects (P = 0.06 and P = 0.08, respectively). From previously published
      coronary risk charts, we estimated the 10-year risk of a coronary heart disease
      (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at
      the time of study, 16 of whom qualified for a diagnosis of the metabolic
      syndrome. CONCLUSIONS: The wide variations in insulin sensitivity and beta-cell
      function found among subjects with NIDDM support the notion that the disorder is
      highly heterogeneous. Reduced insulin sensitivity was clearly related to the
      metabolic syndrome and an increased risk for CHD.

PMID- 12519319
TI  - Pregnancy outcome in Type 1 diabetes mellitus treated with insulin lispro
      (Humalog).
AB  - AIMS: The use of insulin lispro in pregnancy has not been systematically
      investigated despite its increasing use. Pooled data from seven centres with
      experience in the use of insulin lispro were accumulated to evaluate pregnancy
      outcome in women with Type 1 diabetes. METHODS: Seven units with specialist
      obstetric diabetes services were recruited to describe their total experience
      with insulin lispro in pregnancy. Outcomes with respect to the rate of
      miscarriage, congenital abnormality, perinatal mortality and maternal parameters
      were recorded in a standardized format. RESULTS: Outcomes on 71 babies from 76
      pregnancies were documented. There were six (7.8%) early miscarriages. All 71
      babies were liveborn with a mean gestational age of 37.2 weeks, and median
      birthweight of 3230 g. Seven babies weighed > 4 kg. There were four congenital
      abnormalities (5.6%). There was a 72% increase in the mean insulin dose (0.75
      1.29 IU/kg per day). Maternal glycaemic control improved throughout pregnancy. No
      women developed retinopathy de novo during pregnancy and six with established
      retinopathy required laser therapy during pregnancy. CONCLUSIONS: The use of
      insulin lispro in Type 1 diabetes during pregnancy results in outcomes comparable
      to other large studies of diabetic pregnancy.

PMID- 12519320
TI  - Proposed diagnostic thresholds for gestational diabetes mellitus according to a
      75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish
      women.
AB  - AIMS: To study if established diagnostic threshold values for gestational
      diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by
      maternal and perinatal outcomes. METHODS: Historical cohort study of 3260
      pregnant women examined for gestational diabetes on the basis of risk indicators.
      Information on oral glucose tolerance test results and clinical outcomes were
      collected from medical records. RESULTS: There was an increased risk of
      delivering a macrosomic infant in women with 2-h capillary blood glucose of 7.8
      8.9 mmol/l compared with women with 2-h glucose < 7.8 mmol/l. Despite treatment,
      2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with
      increased rates of macrosomia, spontaneous preterm delivery, hypertensive
      complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more
      frequent in women with 2-h glucose > or = 11.1 mmol/l than in women with 2-h
      glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and
      perinatal complications increased with the diagnostic threshold for 2-h glucose.
      Large-scale blinded studies are needed to clarify the question of a clinically
      meaningful diagnosis of gestational diabetes mellitus. Until these results are
      available, a 2-h threshold level of 9.0 mmol/l after a 75-g oral glucose
      tolerance test seems acceptable.

PMID- 12519321
TI  - Long-term outcome after gastrectomy for intractable diabetic gastroparesis.
AB  - AIMS: To examine the long-term outlook for patients with intractable vomiting
      from diabetic gastroparesis who underwent major gastric surgery. METHODS: Of 18
      patients with problems from vomiting referred to the King's Diabetes Centre
      during the years 1994-2000, seven were considered to suffer irreversible symptoms
      not alleviated by protracted periods of medical treatment. They were all Type 1
      Caucasian diabetic women, mean age 32 years (range 28-37 years) with multiple
      symptoms of severe autonomic neuropathy. They underwent major gastric surgery
      comprising 70% gastric resection including pylorus and antrum, with a 60-cm Roux
      en-Y loop of jejunum to prevent reflux gastritis. RESULTS: The vomiting was
      relieved in six of the seven patients almost immediately after surgery and during
      review up to more than 6 years post-operatively. There have been no serious
      relapses, resulting in considerable improvement in quality of life.
      Unfortunately, three of the patients developed renal failure, two of them needing
      renal support treatments 2 and 3 years after successful gastrectomy. One patient
      died suddenly 5 months after successful surgery and one 3 months after starting
      dialysis. CONCLUSIONS: Major gastric surgery can, after careful patient
      selection, effectively relieve distressing vomiting from severe gastroparesis and
      give a greatly improved quality of life to a small group of seriously
      disadvantaged patients where risk of subsequent renal failure is high and where
      life expectancy is poor.

PMID- 12519322
TI  - Clinical characteristics and outcome of pregnancy in women with gestational
      hyperglycaemia with and without antibodies to beta-cell antigens.
AB  - AIMS: To evaluate the prevalence of beta-cell autoantibodies in women with
      gestational diabetes and impaired glucose tolerance, and identify clinical
      characteristics differentiating hyperglycaemic patients with and without
      autoantibodies. METHODS: One hundred and twenty-three pregnant patients with
      gestational diabetes, 84 with impaired glucose tolerance and 290 with
      normoglycaemia were evaluated for anti-islet cell antibodies, glutamic acid
      decarboxylase (GAD) autoantibodies, and the components of the metabolic syndrome.
      RESULTS: Autoantibody positivity was 8.9%, 17.9% and 0.3% in patients with
      diabetes, impaired tolerance and normoglycaemia, respectively. Hyperglycaemic
      patients with autoantibodies had lower body mass index, waist, weight gain at the
      time of the screening test and a lower percentage of previous pregnancies than
      those without autoantibodies. In addition, their fasting insulin values were
      significantly lower and inversely related to the presence of autoantibodies (odds
      ratio (OR) = 0.64; 95% confidence interval (CI) 0.42-0.96), the lowest values
      being found in anti-GAD+ patients. Autoantibody-positive women with diabetes were
      more frequently treated with insulin than negative patients (OR = 7.21; 95% CI
      1.85-28.08). CONCLUSIONS: Autoantibody-positive women with gestational
      hyperglycaemia displayed fewer features of insulin resistance and required more
      frequent insulin therapy than negative women and presumably had presymptomatic
      Type 1 diabetes. If this conclusion is corroborated by the follow-up of larger
      series, clinical and immunological distinction of types of gestational
      hyperglycaemia would be useful.

PMID- 12519323
TI  - Responsiveness of the Problem Areas In Diabetes (PAID) questionnaire.
AB  - AIM: Responsiveness (sensitivity to change over time) is a key psychometric
      quality for an outcome measure. We examined the responsiveness of the Problem
      Areas In Diabetes (PAID) questionnaire, a measure of diabetes-specific emotional
      distress. METHODS: PAID data were obtained from seven diabetes intervention
      studies following a literature search that included both published papers and
      conference abstracts. To estimate responsiveness we used two indices: (i) a
      statistical test (the dependent t-test), and (ii) a commonly used effect size
      index (Cohen's d). RESULTS: Mean patient PAID scores improved from baseline to
      follow-up for all seven studies. Specifically, t-statistics ranged from t= 8.5 (P
      < 0.001) to t= 2.1 (P < 0.06). Effect size results ranged from 0.32 (i.e. small)
      for a disease management intervention to 0.65 (i.e. moderate) for an intensive
      medical/educational intervention. CONCLUSIONS: Despite the pilot nature of the
      studies, the pattern of findings provided strong support for the responsiveness
      of the PAID. Information on responsiveness helps clinical researchers select
      measures, accurately estimate sample size to ensure adequate statistical power,
      and prioritize outcomes to be assessed.

PMID- 12519324
TI  - A protocol for improved glycaemic control following corticosteroid therapy in
      diabetic pregnancies.
AB  - AIMS: Diabetic pregnancies have an increased risk of respiratory distress
      syndrome (RDS) and preterm delivery. Antenatal corticosteroids can prevent RDS
      but induce acute severe hyperglycaemia. We have developed a protocol which
      prevents hyperglycaemia and can be used easily by ward staff. METHODS:
      Intramuscular dexamethasone is given in two doses 12 h apart. Subcutaneous
      insulin and diet are continued but from the first dexamethasone dose until 12 h
      after the second, supplementary intravenous insulin is infused according to
      hourly blood glucose measurements. The protocol incorporates four graded sliding
      scales. The initial scale is selected according to the patient's current
      subcutaneous insulin dose and advanced if the blood glucose is > or = 10.1 mmol/l
      for 2 consecutive hours. RESULTS: In a 10-month period eight (three gestational,
      five pre-gestational) women received antenatal corticosteroids from a total of 37
      diabetic pregnancies. The median amount of supplementary intravenous insulin
      required was 74 U (range 32-88 U); the median glucose values achieved were 5.8
      8.9 mmol/l. Seventy-five percent of glucose measurements were within an
      acceptable range of 4-10 mmol/l. Only one baby developed RDS. DISCUSSION: Large
      amounts of supplementary intravenous insulin are needed to achieve even moderate
      glycaemic control. This protocol enables routine ward staff to manage this
      successfully.

PMID- 12519325
TI  - Treatment with intravenous insulin followed by continuous subcutaneous insulin
      infusion improves glycaemic control in severely resistant Type 2 diabetic
      patients.
AB  - AIMS: Despite high-dose s.c. insulin therapy, some Type 2 diabetes mellitus (DM)
      patients remain in poor metabolic control. We investigated whether a period of
      euglycaemia using i.v. insulin, followed by continuous subcutaneous insulin
      infusion (CSII), would ameliorate the deleterious effects of hyperglycaemia on
      insulin sensitivity and result in sustained, improved metabolic control. METHODS:
      In a prospective observational study, eight Type 2 DM patients with severe
      insulin resistance (insulin dose 1.92 +/- 0.66 U/kg per day (mean +/-sd)), in
      poor metabolic control (HbA(1c) 12.0 +/- 1.7%), were treated with i.v. insulin
      for 31 +/- 10 days aimed at euglycaemia, followed by CSII therapy for 12 months,
      using insulin lispro. Before and after 28 +/- 6 days of i.v. insulin treatment,
      insulin sensitivity was measured by a hyperinsulinaemic euglycaemic clamp.
      RESULTS: Euglycaemia was reached after 12 +/- 6 days of i.v. insulin treatment.
      Subsequently, the i.v. insulin dose required to maintain euglycaemia decreased
      from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg per day (P < 0.005). Whole body glucose
      uptake increased from 12.7 +/- 5.7 to 22.4 +/- 8.8 micromol/kg per min (P <
      0.0005). HbA(1c) decreased to 8.9 +/- 1.2% after 28 +/- 6 days, to 7.1 +/- 0.6%
      after 6 months and to 8.3 +/- 1.4% after 12 months (P < 0.001 vs. pretreatment,
      for all). Lipid profile improved and plasminogen activator inhibitor type 1
      levels decreased significantly. Mean body weight did not change. CONCLUSIONS: In
      Type 2 diabetic patients, who are poorly controlled despite high-dose s.c.
      insulin treatment, a period of 2 weeks of euglycaemia achieved by i.v. insulin
      reverses hyperglycaemia-induced insulin resistance and substantially improves
      metabolic control. Subsequent CSII treatment, using insulin analogues, appears to
      maintain improved metabolic control for at least 1 year. This approach is
      promising but needs further evaluation.

PMID- 12519326
TI  - Feline diabetes--personal experience.

PMID- 12519327
TI  - Is the severity of obstructive sleep apnoea associated with the degree of insulin
      resistance?

PMID- 12519328
TI  - St Vincent's Declaration 10 years on: outcome of diabetic pregnancies.

PMID- 12519330
TI  - Healing after standardized clinical probing of the perlimplant soft tissue seal:
      a histomorphometric study in dogs.
AB  - BACKGROUND/AIMS: Clinical probing of the soft tissues around oral implants has
      become a frequently used parameter for clinical monitoring. However, the healing
      of the disruption of the soft tissue seal as a result of probing has not yet been
      studied. The purpose of this study was to evaluate the healing events in the
      periimplant mucosal tissues following standardized clinical probing. MATERIALS
      AND METHODS: In three foxhounds the mandibular premolars were extracted and,
      after 3 months of healing, TPS screw-shaped implants (ITO Dental Implant System)
      were installed. A plaque control regimen was performed throughout the duration of
      the experiment. After 3 months of healing of the transmucosal implants, clinical
      implant stability and healthy periimplant mucosal tissues with mostly absence of
      bleeding on probing were obtained. Clinical probing of the mesial and distal
      implant sites was performed immediately before 1, 2, 3, 5 and 7 days prior to the
      sacrifice of the animals. A specially manufactured titanium cylinder with a
      mesial and distal groove was fixed to the implants to standardize the insertion
      geometry of a pressure-sensitive probe (0.2-0.25 N, tip diameter 0.45 mm). The
      distances from the alveolar crest to the coronal border of the connective tissue
      adaptation to the implant and the length of the epithelial attachment were
      measured histomorphometrically in nondecalcified ground sections. The buccal and
      lingual aspects of the implants were used to determine the components of the
      biological width in unprobed control sites. RESULTS: The probe caused a
      separation between the surface of the implant and the junctional epithelium, but
      not within the connective tissue adaptation. In general, the probe tip was
      located at the most coronal level of the supracrestal connective tissue as
      determined histologically. By 1 day after separation of the periimplant mucosal
      tissue by probing, an epithelial attachment of approximately 0.5 mm in the apico
      coronal direction was observed. The length of the epithelial adaptation showed a
      tendency to increase over time (day 2: 1.15 mm, day 3: 1.52 mm), and was complete
      at day 5 (1.92 mm). At the unprobed sites the epithelial attachment showed a mean
      length of 1.69 mm. Inflammatory infiltrates were practically nonexistent,
      indicating the absence of tissue trauma or infection as a result of probing.
      CONCLUSIONS: Clinical probing around osseointegrated implants does not appear to
      have detrimental effects on the soft tissue seal and, hence, does not seem to
      jeopardize the longevity of oral implants. The 'healing of the epithelial
      attachment' seems to be complete 5 days after clinical probing.

PMID- 12519331
TI  - Freeze-dried bone for maxillary sinus augmentation in sheep. Part II:
      biomechanical findings.
AB  - This study examines the biomechanical loading capacity of dental implants placed
      in the posterior maxilla in conjunction with subantral augmentation with either
      homogeneous demineralized freeze-dried bone from sheep (s-DFDB) or heterogeneous
      demineralized freeze-dried human bone (h-DFDB) as grafting material in sheep. In
      36 adult female mountain sheep, the Schneiderian membrane was elevated
      extraorally in both maxillary sinuses, and two titanium plasma-flame-sprayed
      cylindrical implants were inserted in each lateral antral wall. Three groups of
      18 maxillary sinuses each were augmented with s-DFDB, h-DFDB and autogenous bone
      from the illiac crest, respectively. In the remaining 18 sinuses, the subantral
      hollow space was left empty. Pull-out tests were carried out after intervals of
      12, 16 and 26 weeks. The mean pull-out force needed, irrespective of time, was
      259.3 N in the empty control group, 356.7 N in the group augmented with
      autogenous bone, 278.1 N in the test group augmented with h-DFDB and 365.2 N in
      the group augmented with s-DFDB, revealing no significant difference between the
      individual groups (P > 0.05). The implants of the group augmented with autogenous
      bone showed an increase in the mean pull-out force from 223.8 N after 12 weeks to
      523.7 N after 26 weeks. The nonaugmented control group yielded values of 248 N
      after 12 weeks, which rose to 269.8 N at the last test, while the values of the h
      DFDB group increased from 275.4 N to 325.4 N. The highest initial pull-out values
      were obtained in the s-DFDB group. They amounted to 310.5 N after 12 weeks and
      rose to 481.4 N after 26 weeks. Time thus proved to have a significant influence
      on the pull-out forces (P = 0.014) with a statistically proven linear trend (P =
      0.007). The findings of this experimental study indicate that the use of
      homogeneous DFDB in one-stage sinus lift procedures results in a mechanical
      loading capacity of implants comparable to that achieved by autogenous cancellous
      bone from the iliac crest. In contrast, the use of heterogenous-DFDB resulted in
      only slightly higher pull-out forces than those observed in the nonaugmented
      control group after 26 weeks.

PMID- 12519332
TI  - Histological assessment of augmented jaw bone utilizing a new collagen barrier
      membrane compared to a standard barrier membrane to protect a granular bone
      substitute material.
AB  - Successful bone augmentation requires predictable space maintenance and adequate
      exclusion of those cells that lack osteogenetic potential from the defect area.
      Natural bone mineral is considered to be osteoconductive and is used as space
      maker in combination with membrane barrier techniques. The aim of this study was
      to compare qualitative histological results achieved by using deproteinized
      bovine bone mineral (DBBM) as a space maintainer and a new collagen barrier
      (Ossix, test group) vs. the same bone substitute and the standard e-PTFE membrane
      (Gore-Tex), control group). Twenty-eight patients were randomly assigned to the
      test or the control group. Seven months after augmentation procedures, biopsies
      were obtained at reentry and were analysed histomorphometrically. In all, 14
      specimens of group I (test group, Ossix) and 13 specimens of group II (controls,
      PTFE-membranes) showed close qualitative similarity of their histologies.
      Histomorphometrically, total mineralized bone area was 42% +/- 18% in group I vs.
      39% +/- 15% in group II. The unmineralized tissue area was 44% +/- 15% vs. 46% +/
      12% and the area of DBBM remnants 14% +/- 9% and 15% +/- 12%, respectively. The
      differences were statistically nonsignificant (Mann-Whitney test). The occurrence
      of barrier exposure did not interfere with the histological outcome either in the
      test or in the control group. The new collagen barrier combined with the DBBM
      provided qualitative bone regeneration comparable to the standard e-PTFE material
      combined with the same mineral.

PMID- 12519333
TI  - Histomorphometric and fluorescence microscopic analysis of bone remodelling after
      installation of implants using an osteotome technique.
AB  - The influence of the osteotome technique on the osseointegration of rough
      surfaced stepped cylinder implants (Frialit)-2) was compared to conventional
      preparation of the implant site in an animal model. A total of 104 implants were
      placed into the distal femoral condyle of 52 New Zealand white rabbits. This
      region contains sufficient trabecular bone for implant placement. The implant
      site was prepared either by the osteotome technique or by conventional technique
      with drills as a control group. During the healing period polychromatic
      fluorescence labelling was performed with four different fluorescent dyes. After
      2, 4 and 8 weeks, the implants were removed with the surrounding bone. The sample
      preparation was done using the 'sawing and grinding' technique. Ground sections
      100 microm thick were used for fluorescence microscopic analysis; 30- microm
      thick ground sections were examined histomorphometrically. After 2 weeks the bone
      to-implant contact ratio was 55.0 +/- 7.1% for the osteotome technique and 29.2
      +/- 4.8% for the control group (P < 0.0005). After 4 weeks, the bone-to-implant
      contact ratio was still significantly better for the osteotome technique (bone-to
      implant contact ratio osteotome technique 71.1 +/- 7.2%, bone-to-implant contact
      ratio control 59.0 +/- 6.3%, P = 0.003). Eight weeks after implant placement the
      bone-to-implant contact ratio was still better for the osteotome technique
      compared to the conventional implant placement. However it was no longer
      statistically significant. The qualitative fluorescence microscopic examination
      showed an earlier and stronger signal for the osteotome technique than the
      control group. With the latter, the zone of mineralization moved slowly towards
      the implant surface. Implant sites prepared by the osteotome technique showed a
      pronounced signal in the whole compressed area already by the second day. In
      conclusion, the osteotome technique increases new bone formation and leads to an
      enhanced osseointegration of dental implants in trabecular bone. However, more
      experimental trials have to be carried out on higher mammals that show a
      metabolic rate of bone that is more comparable to humans.

PMID- 12519334
TI  - Conventional and early loading of unsplinted ITI implants supporting mandibular
      overdentures.
AB  - The aim of this study was to compare the success rates after 1 and 2 years of
      conventionally and early loaded pairs of unsplinted ITI implants supporting
      mandibular overdentures in edentulous patients. Twenty-four participants (age
      range 55-80 years) were randomly allocated with maximum concealment to two
      treatment groups. In the first group, the implants were allowed to heal for 12
      weeks before being functionally loaded (control) and the second group had 6 weeks
      of healing with identical loading. All participants had new conventional complete
      maxillary and mandibular dentures prior to the study. Two sandblasted large-grit
      acid-etched (SLA) surface ITI implants were placed in the mandibular
      interforaminal area, following a standardized nonsubmerged surgical protocol.
      After 6 or 12 weeks of healing, matrices were processed into the fitting surface
      of the pre-existing mandibular dentures and the implants loaded. Implant success
      was determined using mobility tests and radiographs taken at baseline and 52 and
      104 weeks after surgery. Clinical peri-implant parameters were also documented.
      Results showed all implants successfully osseointegrated, according to accepted
      criteria, after 2 years. Mean loss of crestal bone height after 1 year was 0.35
      +/- 0.22 mm (control) vs. 0.27 +/- 0.18 mm (test). After 2 years this reduced to
      0.09 +/- 0.06 mm (control) vs. 0.12 +/- 0.17 mm (test). The mean Periotest value
      after 1 year was -4.9 (control) vs.-3.78 (test). After 2 years, the mean
      resonance frequency value for the control implants was 6797 Hz [mean implant
      stability quotient (ISQ) = 64.77] and for the test implants 6670 Hz (mean ISQ =
      62.0). Shortened loading periods for these ITI implants did not cause any
      statistically significant differences in osseointegration or peri-implant
      parameters. We conclude that pairs of unsplinted SLA-surface ITI implants can be
      successfully loaded with mandibular overdentures 6 weeks after surgery.

PMID- 12519335
TI  - Computer-enhanced stereoscopic vision in a head-mounted display for oral implant
      surgery.
AB  - We developed a head-mounted display (HMD) with integrated computer-generated
      stereoscopic projection of target structures and integrated it into visit, a
      specific oral implant planning and navigation software. The HMD is equipped with
      two miniature computer monitors that project computer-generated graphics
      stereoscopically into the optical path. Its position is tracked by the navigation
      system's optical tracker and target structures are displayed in their true
      position over the operation site. In order to test this system's accuracy and
      spatial perception of the viewer, five interforaminal implants in three dry human
      mandibles were planned with visit and executed using the stereoscopic projection
      through the HMD. The deviation between planned and achieved position of the
      implants was measured on corresponding computed tomography (CT) scan images
      recorded post-operatively. The deviation between planned and achieved implant
      position at the jaw crest was 0.57 +/- 0.49 mm measured from the lingual, and
      0.58 +/- 0.4 mm measured from the buccal cortex. At the tip of the implants the
      deviation was 0.77 +/- 0.63 mm at the lingual and 0.79 +/- 0.71 mm at the buccal
      cortex. The mean angular deviation between planned and executed implant position
      was 3.55 +/- 2.07 degrees. The present in vitro experiment indicates that the
      concept of preoperative planning and transfer to the operative field by an HMD
      allows us to achieve an average precision within 1 mm (range up to 3 mm) of the
      implant position and within 3 degrees deviation for the implant inclination
      (range up to 10 degrees ). Control during the drilling procedure is significantly
      improved by stereoscopic vision through the HMD resulting in a more accurate
      inclination of the implants.

PMID- 12519336
TI  - The relative impact of local and endogenous patient-related factors on implant
      failure up to the abutment stage.
AB  - The aim of the present study was to assess the influence of endogenous and local
      factors on the occurrence of implant failure up to the abutment stage. The study
      comprised a group of 399 consecutive patients, which represented the total of
      patients who had been treated from 1995 to 1997 (with a total of 1263 Branemark
      Bran-system implants) at the Department of Periodontology of the University
      Hospital, Catholic University Leuven. For each patient, the medical history was
      carefully examined. Data collection and analysis were mainly focused on
      endogenous factors such as hypertension, osteoporosis, hypo- or hyperthyroid
      function, chemotherapy, diabetes type I or II, Crohn's disease, some local
      factors (e.g. bone quality, reason for tooth loss) and breach of sterility during
      surgery. The reason for tooth loss, smoking habits, radiotherapy and other local
      bone factors (bone quality and quantity) were also recorded. Implant failures
      were recorded up to the abutment connection. The present study indicated a
      success rate until this stage of 97.8%. General factors such as heavy smoking,
      chemotherapy plus poor bone quality increased implant failure rate. Radiotherapy,
      limited bone volume and claustrophobia, which led to breaching the strict
      preoperative rules of asepsis, appeared to be the most relevant local factors for
      early implant failures.

PMID- 12519337
TI  - Cytokine release by osteoblast-like cells cultured on implant discs of varying
      alloy compositions.
AB  - OBJECTIVE: The aims of this study were (i). to assess the morphological features
      of osteo-blast-like, osteosarcoma cells (cell line SaOS-2) cultured on implant
      surfaces of varying alloys and (ii). to evaluate the biological activity of these
      cells, following their adhesion onto these surfaces. MATERIALS AND METHODS: SaOS
      2 cells (6 x 104) were grown on titanium discs (diameter 30 mm), each with a
      surface of differing composition and roughness (commercially pure titanium,
      titanium-aluminium-vanadium alloy, oxide-blasted titanium and Astra-Tech special
      treatment titanium; the alloys are directly comparable with those used to
      construct implants). The cells were grown for time periods of 1, 3, 5 and 7 days,
      the media were collected and the cells were fixed with 2.5% glutaraldehyde. The
      media were then assayed (using enzyme-linked immunosorbant assay) for the levels
      of interleukin (IL)-1, interleukin-6, interleukin-18 and osteoprotegerin (OPG)
      produced by the cells. The discs, with the cells fixed on them, were viewed under
      scanning electron microscopy (SEM, x 2.0 k) to evaluate cell morphology. RESULTS:
      Following attachment, the cells changed their morphology and released local
      factors known to activate osteoclasts. Commercially pure titanium stimulated the
      cells the most and titanium-aluminium-vanadium alloy the least. All implant
      materials stimulated production of IL-1, IL-6, IL-18 above that produced by cells
      grown on Petri dishes (polystyrene). The titanium-aluminium-vanadium alloy
      allowed cell attachment but levels of IL-1 in this medium were significantly
      lower (31.5 +/- 5.2 pg/ml on same day) than cultures with pure titanium (201.8 +/
      11.5 pg/ml at day 5). The same pattern was observed with the IL-6, IL-18, and
      OPG with polystyrene appearing to stimulate most production of OPG. Titanium
      aluminium-vanadium produced the least biological response.

PMID- 12519338
TI  - Local administration of growth hormone enhances periimplant bone reaction in an
      osteoporotic rabbit model.
AB  - OBJECTIVE: The purpose of this study was to determine whether rhGH administered
      locally during the surgical placement of an implant, in the tibia of an
      osteoporotic rabbit model, would induce qualitative and quantitative differences
      in peri-implant bone reaction. MATERIALS AND METHODS: Eight New Zealand rabbits
      were ovariectomized and fed with a low-calcium diet (with 0.07% of calcium) to
      induce osteoporosis. After 6 weeks, an experimental titanium sheet was inserted
      into the rabbit tibiae. The rabbits were randomly divided into two groups. The
      experimental group was treated with 4 IU of rhGH added locally into the ostectomy
      as a lyophilized powder and the control group was left without any treatment.
      After 2 weeks, animals were sacrificed, tibial sections were prepared and bone
      titanium interface was examined at light microscopy, using Masson, hematoxylin
      eosin and Pichrosirius stains. Light microscopic morphometry and densitometry
      were used to comparatively quantitate bone reaction. RESULTS/CONCLUSION: Local
      administration of rhGH during the surgical placement of titanium sheets on the
      tibiae of an osteoporotic rabbit model enhances periosteal and transcortical
      reaction and mineralization of osteoid 14 days later around titanium sheets,
      without increasing bone resorption.

PMID- 12519340
TI  - The palatal advanced flap: a pedicle flap for primary coverage of immediately
      placed implants.
AB  - The placement of implants immediately after tooth extraction has become a
      relatively common event. This approach has gained popularity because it reduces
      the time between tooth extraction and placement of the final prosthetic
      restoration. One problem that remains unresolved with this procedure, however, is
      that there is usually space left in the area surrounding the coronal portion of
      the implant. As none of the techniques published to date is completely
      satisfactory, we developed an approach that is a modification of the palatal
      pedicle flaps used for closure of oro-antral fistulas. This technique allows for
      precise rotational advancement of the palatal tissue in a coronal direction, thus
      facilitating complete coverage of the extraction site. The procedure was used on
      38 patients treated for primary coverage of postextraction placed implants.
      Thirty-two of the patients required single tooth replacement, three patients
      received two implants each, and three patients received three implants each. In
      27 of the cases, the procedure was performed in conjunction with barrier
      membranes; of the 38 cases, 25 patients required the use of DFDBA to fill the
      defect created by the extraction procedure. The average defect width was 4.70 +/-
      0.2 mm. Complete primary coverage was obtained in all cases without any changes
      in the size or anatomy of the buccal vestibule; complete coverage was maintained
      over the entire healing period of 6-8 months (mean +/- SEM, 6.49 +/- 0.10
      months). Even with guided tissue regeneration cases, there was no exposure of the
      barrier membrane or cover screw of the implant during healing. After a period of
      1-5 years (mean +/- SEM, 39.35 +/- 2.69 months), none of the implants was lost.
      We conclude that the palatal advanced flap procedure is useful, fast, and easy to
      perform in cases of immediate implant placement after tooth extraction.

PMID- 12519339
TI  - Osteocalcin, deoxypyridinoline and interleukin-1beta in peri-implant crevicular
      fluid of patients with peri-implantitis.
AB  - The aim of the present study was to analyze the levels of osteocalcin,
      deoxypyridinoline (Dpd) and interleukin-1beta as markers of bone metabolism in
      peri-implant crevicular fluid (PICF) from peri-implantitis patients. PICF was
      sampled from a total of 34 endosseous titanium implants from 16 patients; nine
      females (mean age 52.8, range 40-62 years) and seven males (mean age 56.0, range
      36-66 years). The implants had been in place for a period of 9-112 months (mean;
      35.8 months) since the loading. These sites were categorized as six peri
      implantitis, eight peri-implant mucositis and 20 healthy implant. PICF volume
      from peri-implantitis sites was significantly higher than mucositis and healthy
      implant sites (P < 0.01). Osteocalcin levels in PICF from mucositis sites were
      significantly higher than healthy implants (P < 0.05), whereas peri-implantitis
      sites were not significantly different from either mucositis or healthy implant
      sites. Dpd could not be detected in any of the samples examined. IL-1beta levels
      in PICF from peri-implantitis sites were significantly higher than levels from
      peri-implant mucositis (P < 0.05) and healthy implant sites (P < 0.01). In
      conclusion, osteocalcin in PICF may reflect increased local bone turnover around
      implants. Further, IL-1beta should be a useful marker for peri-implant
      inflammation.

PMID- 12519341
TI  - Precision of transfer of preoperative planning for oral implants based on cone
      beam CT-scan images through a robotic drilling machine.
AB  - In this study, an image-guided system for oral implant placement was assessed. A
      specially designed mechanical tool has been elaborated to transfer the
      preoperative implant axis planned on 3-dimensional imagery into a surgical
      template by a numerically controlled drilling machine. The main drawback of image
      guiding systems is the use of preoperative computed tomography, which is
      expensive and delivers high radiation doses. Therefore, in this study the image
      guiding system was coupled with a cone-beam tomograph that significantly
      decreased both cost and radiation doses. Three edentulous models were used. To
      determine the accuracy of the system, the ability of a 1.8-mm diameter drill to
      enter a 2.0-mm diameter, 10-mm-long titanium tube inserted on the model with no
      contact was verified. Because the drill entered the tubes with no contact and
      went beyond the end of the tube, the transfer error was less than 0.2 mm for
      translation and less than 1.1 degrees for rotation. The method presented here is
      low cost and high precision compared to other technological solutions such as
      tracking. Further assessment in the surgical field should lead to daily use of
      this system for flapless surgery, to prepare a prosthesis prior to surgery for
      immediate loading, to reduce risk of injuring critical anatomical structures and
      to eliminate manual placement error.

PMID- 12519342
TI  - Three-dimensional finite element analysis of implant stability in the atrophic
      posterior maxilla: a mathematical study of the sinus floor augmentation.
AB  - Sinus lifting is performed with a variety of materials and techniques without a
      precise knowledge of the quantity of augmentation. This study based on three
      dimensional finite element analysis was designed to show which surgical procedure
      and which amount of peri-implant packing yields the best bony support for dental
      implants. Eight 3D-FE models were used. Four modeled standard situations
      simulated quantitatively different packing situations produced by differences in
      surgical approach: i. no packing; ii. thin 1 mm bony sheath; iii. oblique
      subcomplete packing; iv. complete bony peri-implant packing up to the implant
      end. A fifth model compared a standard implant with a length of 13.5 mm and a
      diameter of 3.75 mm with a 7-mm-long and 5-mm-thick implant. In three additional
      models the stress response of the bone-implant system was evaluated in the
      absence of a cortical layer, thus simulating an extreme degree of maxillary
      atrophy. In all models the modeled implants were loaded at their points of
      emergence with an assumed force of 100 N. The vector of the loading force was
      inclined 30 degrees posteriorly relative to the implant axis and 30 degrees away
      from the sagittal plane. The bone-implant interface was assumed to be perfect
      simulating full osseointegration. The final evaluation of the FE models showed
      complete peri-implant packing to reduce displacements of the implant tip by 32%
      vs. no sheathing/packing. Van Mises' equivalent stresses were used to assess the
      stresses in both human bone and titanium alloy implants. The highest stress
      levels in bone were predicted for the case without sufficient implant sheathing.
      In the models with adequate bony implant support, intrabony stresses were
      generally reduced by up to - 40%. The structural stiffness of the bone-implant
      system increased with the extent of sinus floor elevation. The results indicate
      that more extensive peri-implant packing reduces implant displacement, intrabony
      stresses and stresses at the bone-implant interface.

PMID- 12519343
TI  - Analysis of a device for assessment of abutment and prosthesis screw loosening in
      oral implants.
AB  - Screw loosening is an irritating problem in implant dentistry. Loosened abutment
      screws and prosthesis screws are often found at yearly examinations. Loosened
      screws may cause costly complications, such as screw fractures and fracture of
      the framework, and methods to prevent them would be welcome. The purpose of this
      study is firstly to describe a mechanical protractor device designed to fit the
      electrical Torque Controller (Nobel Biocare, DEA 020, Gothenburg, Sweden) and
      measure the number of degrees necessary to retighten the abutment screw or the
      prosthesis screw to reach the target torque value. A second purpose is to analyse
      the precision and validity of the device. The results of the study indicate that
      the degree of preset loosening of abutment and prosthesis screws can be well
      reflected in the number of degrees necessary for retightening. It was also shown
      that it is possible to retighten the abutment and prosthesis screws with a
      precision of 1.7 degrees and 1.3 degrees, respectively. The study shows that the
      device has good precision and validity. By using this device, we hope to be able
      to evaluate various parameters for screw stability, such as the type of implant
      system, the number of fixtures, the type of abutments, the type of bridge
      material and the need for retightening of the abutment and prosthesis screws.

PMID- 12519344
TI  - Is antimicrobial resistance also subject to globalization?
AB  - In recent years one of the more alarming aspects of clinical microbiology has
      been the dramatic increase in the incidence of resistance to antibacterial agents
      among pathogens causing nosocomial as well as community-acquired infections.
      There are profound geographic differences in the incidence of resistance among
      pathogens of the respiratory tract, only some of which can be explained by the
      local use of antibiotics. A high percentage of Moraxella catarrhalis strains
      produce beta-lactamase and are thus resistant to many beta-lactam antibiotics. In
      contrast, beta-lactamase production among strains of Haemophilus influenzae
      rarely reaches more than 30% around the world. Methicillin-resistance in
      Staphylococcus aureus is a common and increasing problem in hospitals but its
      extent varies both locally and nationally. Resistance is usually associated with
      the local spread of resistant strains. High standards of hygiene in hospitals can
      prevent the spread of such strains but once established they can be difficult to
      eradicate. Although Streptococcus pyogenes remains highly susceptible to
      penicillins, even after many decades of their use, resistance to macrolides has
      occurred. This resistance can rise and fall. Although the increase of macrolide
      resistance in S. pyogenes can often be associated with an increase in the use of
      these drugs, this is not always so. In some cases it has been shown to be caused
      by the spread of one or more resistant clones. Eradication of these clones can
      reduce the level of resistance markedly. Resistance to both macrolides and
      penicillins among strains of Streptococcus pneumoniae is seen world-wide but is
      highly variable from country to country. Local habits of drug usage may play a
      part. In Italy, for example, there is preference for the use of parenteral third
      generation cephalosporins for some severe infections and there is a corresponding
      low level of penicillin-resistance among pneumococci.

PMID- 12519345
TI  - The era of antimicrobial resistance-implications for the clinical laboratory.
AB  - The emergence of resistance to antimicrobial drugs in a range of bacterial
      pathogens of the respiratory tract creates a challenge for the clinical
      diagnostic laboratory. Resistance to macrolides among strains of Streptococcus
      pneumoniae has reached high levels in many countries. There are two main types of
      resistance mechanisms, one (MLSB phenotype) leading to high-level resistance and
      the other (M phenotype) resulting in a lower level of resistance. As there are
      indications that high-level resistance may have clinical relevance, it is
      important to be able to detect such strains. This is now possible with the
      erythromycin/clindamycin double disc diffusion test. Although resistance to beta
      lactams has also increased, there is now evidence that some beta-lactams are
      still effective against isolates that have low-level resistance. In response to
      these observations, new breakpoints have now been introduced by the National
      Committee for Clinical Laboratory Standards (NCCLS) for amoxicillin, cefotaxime
      and ceftriaxone, which increase the percentage of pneumococcal isolates that can
      still be treated effectively with these agents. As a consequence of the
      increasing use of fluoroquinolones, resistance has now emerged to this group of
      compounds and this has been associated with clinical failures. Although standard
      minimum inhibitory concentration tests can detect strains with high levels of
      resistance (double step mutants) they are not reliable in detecting strains with
      a single mutation. This is important as there is increasing evidence that strains
      with a single mutation in the target topoisomerase are even more likely to
      develop a second mutation, leading to higher levels of resistance and thus
      probably, therapeutic failure. Because resistance to fluoroquinolones is
      currently low in the US, the NCCLS does not recommend that susceptibility testing
      with the newer respiratory fluoroquinolones be carried out routinely. However,
      since the respiratory fluoroquinolones have in fact become the first line of
      therapy for the treatment of community-acquired pneumonia, it may now be time to
      institute routine testing of clinical isolates of pneumococci to these agents.
      Simple techniques for the clinical diagnostic laboratory to enable these first
      step mutants to be detected are urgently required.

PMID- 12519346
TI  - Bacterial resistance--the clinical challenge.
AB  - Resistance to antibacterial agents has increased among many species of bacterial
      pathogens in the last two decades. While this has been recognized and has been a
      matter of concern among those concerned with infectious diseases, it is only
      relatively recently that prescribing physicians have become aware of the problem.
      A range of official bodies, both national and international, have proposed a
      range of strategies for controlling this increase in resistance. The relationship
      between resistance and clinical efficacy or failure is unclear in many areas,
      although increasingly resistance can be seen to be associated with a less than
      optimal clinical response. Although the relationship between antibiotic use and
      resistance is complex, there is an assumption that excessive use of
      antibacterials may drive an increase in resistance. The term 'prudent
      prescribing' is frequently used in official documents, but it is not easy for the
      prescriber to determine exactly what is prudent prescribing. There have been
      efforts to reduce the unnecessary use of antibacterials in the treatment of many
      community respiratory infections where the etiological agent is likely to be
      viral. Guidelines for prescribing have been drawn up by governments and
      professional societies but their impact can be variable. They need to take
      account of the changing patterns of resistance, for example the rise in high
      level penicillin resistance among pneumococci. They also need to be readily
      accessible to the practicing clinician. Surveillance systems are available in
      abundance and these may be local, national, or international. They often,
      however, suffer from drawbacks and are frequently selective. Frequently the
      prescriber does not have ready access to the most appropriate data. Integrated
      strategies to control resistance are urgently needed, as are improved rapid
      diagnostic facilities.

PMID- 12519349
TI  - Human granulocytic ehrlichiosis in Europe.
AB  - Ehrlichiosis comprises a group of emerging tick-borne infectious diseases caused
      by obligate intracellular Gram-negative bacteria that infect leukocytes.
      Infections caused by members of the genus Ehrlichia have been described in
      animals and humans, but to date there are no convincing reports of the presence
      of other types of human ehrlichiosis different from human granulocytic
      ehrlichiosis (HGE) in Europe. The European vector is the same as that of Lyme
      borreliosis, the hard tick Ixodes ricinus, and HGE has a similar epidemiology to
      that of Borrelia burgdorferi infection. Across Europe, I. ricinus is infected to
      a variable extent (0.4-66.7%) with the causative agent Ehrlichia (Anaplasma)
      phagocytophila genogroup, and since its first description in Slovenia in 1997,
      details of 15 patients have been published. Diagnosis requires careful
      consideration of all circumstances and symptoms (history of tick bite and the
      presence of a flu-like syndrome with variable degrees of anemia,
      thrombocytopenia, and leukopenia, and elevated liver enzymes). Some differences
      can be seen between US and European HGE patients. European HGE cases have a less
      severe course, and the presence of morulae is uncommon. In Europe, verification
      of HGE has been based on PCR and immunofluorescence antibody tests, because no
      isolation from humans has been reported.

PMID- 12519350
TI  - Pre-emptive oral ganciclovir can reduce the risk of cytomegalovirus disease in
      liver transplant recipients.
AB  - A cohort of 65 liver transplant recipients was prospectively monitored with
      qualitative polymerase chain reaction (PCR) in plasma. The first 25 patients did
      not receive prophylaxis. From a consecutive group of 40 recipients, 11 high-risk
      patients donor CMV-seropositive/receptor CMV-seronegative (D+/R-), persistent CMV
      replication) received pre-emptive oral ganciclovir (1000 mg three times daily),
      when a marker of risk was identified, until day 90. The overall incidence of
      cytomegalovirus (CMV) disease at six months was 20% (five of 25 patients) in the
      non-prophylaxis group and 2.5% (one of 40 patients) in the group treated with pre
      emptive oral ganciclovir (relative risk, 0.11; 95% confidence interval; 0.01
      0.96; P = 0.04). The PCR sensitivity for detecting CMV disease was 80%, the
      specificity was 90%, and the positive and negative predictive values were 66% and
      95%, respectively. Adverse events, graft rejection and survival were similar
      between groups. We conclude that pre-emptive oral ganciclovir in high-risk
      patients can reduce the risk of CMV disease.

PMID- 12519351
TI  - Correlation between the activity of different fluoroquinolones and the presence
      of mechanisms of quinolone resistance in epidemiologically related and unrelated
      strains of methicillin-susceptible and -resistant Staphylococcus aureus.
AB  - OBJECTIVE: To study the activity of five different fluoroquinolones against 22
      epidemiologically related and unrelated strains of Staphylococcus aureus (13
      methicillin-resistant (MRSA) strains and nine methicillin-susceptible (MSSA)
      strains) in which the mechanisms of quinolone resistance are also investigated.
      METHODS: The MICs of the different fluoroquinolones were determined by the
      microdilution method, in the presence and absence of reserpine. The quinolone
      resistance-determining regions of the gyrA, gyrB, grlA and grlB genes were
      amplified and sequenced to establish the presence of mutations. The molecular
      epidemiology of the 22 strains was performed by low-frequency restriction
      analysis of chromosomal DNA with SmaI. RESULTS: MSSA strains showed lower
      homology than MRSA strains, in which only two clones were seen. Trovafloxacin
      showed the best activity against these clinical isolates of S. aureus, since
      strains carrying one amino acid change in both GyrA and GrlA subunits remained
      susceptible to this antimicrobial agent. Furthermore, trovafloxacin did not seem
      to be a substrate for NorA. CONCLUSION: Trovafloxacin was the most active
      quinolone tested against S. aureus strains, followed by levofloxacin and
      sparfloxacin, whereas ciprofloxacin and norfloxacin were the least active
      quinolones, in both the presence and absence of reserpine. Epidemiologically
      related S. aureus strains presented different mechanisms of quinolone resistance,
      suggesting a divergent evolution of the same clone. Finally, 16 S. aureus strains
      with a ciprofloxacin plus reserpine MIC > or = 1 mg/L already showed a mutation
      in the grlA gene. This MIC may be useful as a marker of mutation in this gene,
      contraindicating the use of this quinolone, since a second mutation may develop
      during treatment.

PMID- 12519352
TI  - Multicentre assessment of linezolid antimicrobial activity and spectrum in
      Europe: report from the Zyvox antimicrobial potency study (ZAPS-Europe).
AB  - OBJECTIVE: To evaluate the in vitro spectrum and activity of linezolid, a recent
      oxazolidinone, according to well-controlled surveillance data from 42 medical
      centers in 13 countries throughout Europe. METHODS: Participants tested the
      susceptibility of 125 clinical strains of enterococcal and staphylococcal species
      against 13 drugs using reference broth microdilution trays or the standardized
      disk diffusion method of the National Committee for Clinical Laboratory Standards
      (NCCLS). Streptococcal species (n = 25 at each center) were tested against six
      drugs using E test (AB BIODISK, Solna, Sweden). Quality assurance testing was
      conducted using NCCLS-recommended strains and verification of resistance to
      linezolid and other selected agents was performed by retesting strains at the
      regional (Europe) and international (USA) monitor sites. RESULTS: A total of 5598
      strains from throughout Europe (91% compliance) were tested. Vancomycin
      resistance was reported in only 0.6 and 3.0% of Enterococcus faecalis and E.
      faecium, respectively. Penicillin resistance occurred in 25.1% of Streptococcus
      pneumoniae; 4.9% at the high-level (> or =2 mg/L). The MIC90 for linezolid was 1
      mg/L for streptococci and 2 mg/L for enterococci and staphylococci. Using the US
      FDA- and EUCAST-recommended susceptible breakpoints for linezolid, there were no
      confirmed reports of linezolid resistance [minimum inhibitory concentration
      (MIC), > or =8 mg/L]. The distribution of linezolid MIC values was unimodal and
      varied between 0.25 and 1 mg/L for streptococci (>90% of isolates), and between 1
      and 2 mg/L for staphylococci (>90%) and enterococci (>95%). There were no
      differences in linezolid susceptibility in the vancomycin-, oxacillin-, or
      penicillin-resistant subsets of strains when compared to susceptible organism
      populations. CONCLUSIONS: Compared to the North American component of this study,
      there was substantially less vancomycin resistance among E. faecium isolates
      (Europe 3.0% vs. North America 63.4%). While the occurrence of penicillin
      resistant S. pneumoniae in Europe and North America was similar (25.1% vs.
      29.7%), the recovery of high-level penicillin-resistant strains was nearly three
      fold higher in North America (4.9% vs. 13.2%). Only linezolid was universally
      active against all the tested Gram-positive isolates at </=4 mg/L.

PMID- 12519353
TI  - Clinical microbiological case: severe relapsing septal panniculitis in a healthy
      man from the south-eastern USA.

PMID- 12519354
TI  - Pyosalpinx: not always a sexual transmitted disease? Pyosalpinx caused by
      Plesiomonas shigelloides in an immunocompetent host.
AB  - Plesiomonas shigelloides are ubiquitous Gram-negative bacteria that are found in
      fresh or marine water, particularly in tropical or warm climates; they were
      recently implicated in diarrhoeal disease. Patients usually present with a
      history of recent travel to tropical regions or consumption of uncooked seafood.
      Extraintestinal disease has rarely been reported, occurring generally in neonates
      or immunocompromised patients, and is often fatal. We report a case of right
      pyosalpinx due to P. shigelloides acquired by swimming in contaminated water.
      Laparoscopic salpingectomy led to a good outcome.

PMID- 12519355
TI  - Pneumonia due to Candida krusei.
AB  - A case of post-transplantation pneumonia due to Candida krusei is reported. A 42
      year-old man was admitted 28 days after heart transplantation with cough,
      pleuritic pain and fever. A chest computed tomograph showed multiple alveolar
      infiltrates bilaterally. He received broad-spectrum antibiotics, fluconazole for
      oral candidiasis, and cotrimoxazole for possible Pneumocystis carinii. A short
      lived period of improvement was followed by respiratory failure. Cultures of
      bronchial washings grew C. krusei and C. albicans. The infection was documented
      by histology and culture obtained by transthoracic aspiration. Treatment with
      amphotericin B was initiated, but the patient died. Histology and culture of a
      pulmonary specimen, obtained immediately post mortem, further documented the
      infection with C. krusei.

PMID- 12519356
TI  - In vitro effects of cefotaxime and ceftriaxone on Salmonella typhi within human
      monocyte-derived macrophages.
AB  - The main objective of this in vitro study was to assess the effects of cefotaxime
      and ceftriaxone in killing Salmonella typhi in infected human macrophages. Human
      monocyte-derived macrophages isolated from peripheral blood of human volunteers
      were cultured in vitro for macrophage differentiation, and subsequently infected
      with S. typhi strains (a clinical isolate and a standard strain TA-42) at a cell
      ratio of 10 : 1. MICs of cefotaxime and ceftriaxone were determined by broth
      microdilution, and the antibiotics were included in the culture medium at one and
      five times their MIC values. Samples of cell culture medium taken at 0, 3, 6 and
      24 h of incubation were cultured for growth of S. typhi on nutrient agar.
      Gentamicin (10 mg/L) was included in each well except for the control wells, in
      order to prevent growth of extracellular S. typhi. Both antibiotics showed good
      in vitro antibacterial effects against S. typhi strains. There were no
      statistically significant differences between the extracellular and intracellular
      effects of antibiotics with regard to elimination of the bacteria. Cefotaxime and
      ceftriaxone are highly effective against extracellular bacterial growth. The
      results of our in vitro experiments suggest that cefotaxime and ceftriaxone might
      also be used clinically against susceptible intracellular pathogens such as S.
      typhi.

PMID- 12519357
TI  - In vitro anti-anaerobic activity of the cephalosporin derivative RWJ 54428,
      compared to seven other compounds.
AB  - Agar dilution MIC was used to test the activity of RWJ 54428, a new cephalosporin
      derivative, compared to imipenem, meropenem, ceftriaxone, piperacillin,
      piperacillin-tazobactam, clindamycin and metronidazole against 363 anaerobes
      isolated from clinical specimens. RWJ 54428 had low MICs against most beta
      lactamase-negative Gram-negative rods, and all Gram-positive strains except
      Clostridium difficile. Imipenem and meropenem had the lowest MICs (MIC50s of
      0.125 mg/L and MIC90s of 1.0 mg/L). Piperacillin-tazobactam, clindamycin and
      metronidazole were active against most strains, and ceftriaxone was active mainly
      against beta-lactamase-negative organisms.

PMID- 12519358
TI  - Cephalosporinase induction and cephalosporin resistance: a longstanding
      misinterpretation.

PMID- 12519359
TI  - Aseptic meningitis as a delayed neurologic complication of murine typhus.

PMID- 12519360
TI  - Arcanobacterium hemolyticum: identification and susceptibility to nine
      antimicrobial agents.

PMID- 12519363
TI  - Sib-pairs in multifactorial disorders: the sib-similarity problem.
AB  - Common disorders are, by definition, the major cause of ill health and death.
      Most can be modified by avoiding or shielding an environment, as in sunburn and
      coeliac disease, by replacing some deficient substance, as in diabetes or
      myxoedema, or by empirical methods of evident effect as in schizophrenia and
      depressive illness. As expected, all show an increased incidence in relatives and
      the identification of the more influential loci involved may define unexpected
      links in the metabolic map: these may be amenable to therapy, or, in autoimmune
      disorders and asthma, define precipitating factors by sequencing the receptor
      involved. The major investment in trawling the genotype for influential loci has
      been by affected sib-pairs with parents (ASPs). Over a hundred major studies have
      been published with very limited success. No substantial study of normal sib
      pairs has been undertaken, making this family of surveys one of the largest
      undertaken in the absence of controls. Possible reasons for this limited success
      and the many suggestive false positives are considered.

PMID- 12519367
TI  - Genetic technologies, health care policy and the patent bargain.
AB  - The idea of granting patents on human genetic material continues to cause
      controversy. The debate is largely focussed on the moral acceptability of human
      gene patents, the impact of gene patents on the research environment and the
      value of patents to stimulate innovation and the commercialization and
      dissemination of genetic discoveries. As highlighted by a recent controversy in
      Canada, patents can also have a profound effect on health policy and access to
      genetic services. Creative and bold patent reform initiatives are necessary to
      ensure that society will, to the highest degree possible, reap the health care
      benefits of the genetic revolution.

PMID- 12519368
TI  - The TaqIB and -629C>A polymorphisms at the cholesteryl ester transfer protein
      locus: associations with lipid levels in a multiethnic population. The 1998
      Singapore National Health Survey.
AB  - The Singapore population comprises Chinese, Malays and Asian Indians. Within this
      population, Asian Indians have the highest rates of coronary heart disease,
      whereas Chinese have the lowest. Conversely, Indians have the lowest high-density
      lipoprotein cholesterol (HDL-C) concentrations, followed by Malays and Chinese.
      We studied the TaqIB and -629C>A polymorphisms at the CETP locus in 1300 Chinese,
      364 Malay and 282 Asian Indian men, and in 1558 Chinese, 397 Malay and 306 Asian
      Indian women, to determine whether these polymorphisms are responsible for the
      ethnic difference in HDL-C concentration. The frequency of the B2 allele in
      Chinese, Malays and Indians was 0.384, 0.339 and 0.449 in men, and 0.379, 0.329
      and 0.415 in women, respectively (p < 0.001). For the A-629 allele, the relative
      frequencies were 0.477, 0.423 and 0.592 in men and 0.486, 0.416 and 0.575 in
      women (p < 0.001). The two polymorphisms were in linkage disequilibrium (D /
      Dmax= 0.9772, p < 0.00001). The B2 and the A-629 alleles were associated with
      increased HDL-C concentrations in a dose-dependent manner. The B2 allele
      continued to show an association with HDL-C concentration, even after controlling
      for the genotype at position -629. Dietary cholesterol showed a significant
      interaction with the TaqIB polymorphism in determining HDL-C concentrations in
      Indians and Malays, but not in Chinese. In conclusion, the high frequencies of
      these polymorphisms in Asian Indians could not explain the observed ethnic
      differences in HDL-C concentration. Moreover, we observed an ethnic-specific
      interaction among dietary cholesterol, the TaqIB polymorphism and HDL-C
      concentrations.

PMID- 12519369
TI  - The association of cholesteryl ester transfer protein polymorphism with high
      density lipoprotein cholesterol and coronary artery disease in Koreans.
AB  - Cholesteryl ester transfer protein (CETP) is a key protein involved in high
      density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma
      HDL-C levels, and its genetic regulation may be involved in the development of
      coronary artery disease (CAD). The aim of this study was to determine the
      frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its
      relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients
      with significant CAD and 106 controls were examined with respect to their
      genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies
      of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and
      34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other
      ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C
      levels in females (p = 0.049) and non-smoking males (p = 0.037). After
      controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism
      was still significantly associated with HDL-C levels (p = 0.046) and explained
      5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1
      homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed
      by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote
      was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence
      interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B
      polymorphism is associated with low HDL-C levels in females and non-smoking
      males, and may be an independent genetic risk factor of CAD in the Korean
      population.

PMID- 12519370
TI  - A second kindred linked to DFNA20 (17q25.3) reduces the genetic interval.
AB  - A family ascertained in the United States displays significant evidence of
      linkage to 17q25.3 (maximum two-point LOD score 6.32). The non-syndromic
      autosomal-dominant hearing-loss loci DFNA20 and DFNA26 map to this region. The 3
      unit support interval and haplotype for this USA kindred falls within the
      interval for DFNA20 and DFNA26 and reduces the region to 6.05 cM, according to
      the deCode genetic map. The same gene is probably responsible for both
      DFNA20/DFNA26. In addition, the USH1G locus maps to this region and could be an
      allelic variant of the gene responsible for DFNA20/DFNA26. Clinical data is
      presented for this kindred, where hearing-impaired family members present with
      sloping audiograms with mid- and high-frequency hearing loss, which progresses to
      hearing loss that affects all frequencies. The mean age of onset of hearing
      impairment is 13.2 years of age (standard deviation: 4.6 years).

PMID- 12519371
TI  - Fabry disease: a functional and anatomical study of cardiac manifestations in 20
      hemizygous male patients.
AB  - Fabry disease (FD, OMIM 301500) is an X-linked disorder of glycosphingolipid
      metabolism resulting from the deficient activity of alpha-galactosidase A, a
      lysosomal acid hydrolase, leading to progressive lysosomal accumulation of
      incompletely metabolized neutral glycosphingolipids. Cardiac involvement is
      frequent. The objective of this study was to characterize the cardiac
      abnormalities in male patients affected with classic Fabry disease and define the
      context in which the clinicians were able to make the diagnosis. Clinical
      evaluation, laboratory tests, electrocardiography (ECG) and echocardiography were
      performed in 20 hemizygous men (mean age 39 years, range 12-65 years). The
      context of diagnosis was obtained by review of patients' charts. Left ventricular
      hypertrophy (LVH) and/or concentric remodeling were found in 12 patients (60%).
      Structural changes in mitral and aortic valves were found in 25% and 10% of
      cases, respectively. The sensitivity of the ECG Romhilt-Estes score for LVH was
      high (80%). Short PR interval (40%), ST segment abnormalities and conduction
      delay were frequent on ECG. Left ventricular mass index, ECG scores for LVH and
      systolic pulmonary pressure correlated positively with age. There was no relation
      between classic vascular risk factors and coronary artery disease, transient
      ischemic attack (TIA) or stroke. Diagnosis of Fabry disease was frequently
      suggested by nephrologists, dermatologists or geneticists. Echocardiograph and
      ECG abnormalities are frequently observed in patients with Fabry disease.
      Cardiologists should be aware of the diagnosis of Fabry disease in patients
      presenting with LVH, concentric remodeling, mitral and aortic valve thickening on
      echocardiography, short PR interval and conduction defects on ECG.

PMID- 12519372
TI  - Polymorphisms at the SRBI locus are associated with lipoprotein levels in
      subjects with heterozygous familial hypercholesterolemia.
AB  - Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved
      in the pathophysiology of atherosclerosis. We have examined the association of
      three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous
      for familial hypercholesterolemia (FH). The alleles represented by polymorphisms
      in exon 1 and exon 8 were associated with variation in plasma concentrations of
      fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the
      most common allele, and for heterozygotes and homozygotes for the less common
      allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and
      96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment
      for age, sex and body mass index. In addition, the exon 8 polymorphism was
      associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18
      mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9,
      15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL)
      cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041)
      concentrations. In agreement with animal studies, our data also suggest a role
      for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins
      in humans. This pathway may constitute a backup mechanism to LDL receptor
      mediated pathways for the catabolism of these lipoproteins, which could be
      particularly relevant in subjects with high levels of apoB-containing
      lipoproteins, such as those occurring in patients with FH.

PMID- 12519373
TI  - A novel point mutation of the androgen receptor (F804L) in an Egyptian newborn
      with complete androgen insensitivity associated with congenital glaucoma and
      hypertrophic pyloric stenosis.
AB  - Androgen-insensitivity syndrome (AIS) is a major cause of male
      pseudohermaphroditism (MPH). Although AIS is usually reported as a monogenic
      disease resulting from androgen receptor (AR) mutations, on rare occasions it has
      been observed as part of a multiple congenital anomaly syndrome. We report here a
      patient who was the first newborn girl of an unrelated couple. Shortly after
      birth, the diagnoses of congenital glaucoma and pyloric stenosis were made. A
      detailed history of the father's family revealed that nine members presented
      glaucoma before 40 years of age. Clinical and ultrasound evaluation showed two
      inguinal testes, with female external genitalia and no Mullerian derivatives. The
      patient had a 46,XY karyotype, good testicular response to gonadotrophin
      stimulation and a remarkably high T : dihydrotestosterone ratio. Sequencing of
      the five exons of the 5alpha-reductase type 2 gene (SRD5A2) was normal.
      Conversely, a de novo point mutation was found in exon 6 of the AR gene,
      resulting in an F804L substitution, which has never been described previously. To
      our knowledge, the association of complete AIS, congenital glaucoma and pyloric
      stenosis has also never been reported previously.

PMID- 12519374
TI  - Very low incidence of microsatellite instability in rectal cancers from families
      at risk for HNPCC.
AB  - In families at risk for hereditary non-polyposis colorectal cancer (HNPCC) that
      do not fulfill all clinical criteria for HNPCC, additional evidence is sought by
      testing cancer specimens for microsatellite instability (MSI). We investigated
      whether the location of a colorectal cancer (CRC) predicts the result of MSI
      testing in these families. One hundred and seven patients suspected for HNPCC
      were offered MSI-testing. MSI-testing was positive in 6/7 patients with
      endometrial carcinoma and in 22/100 patients with CRC. Only one out of 22 (4%)
      rectal cancers was MSI-positive, and in this patient no mismatch repair (MMR)
      gene mutation was found. Right-sided colon carcinomas were more likely to be MSI
      positive (14/37 or 38%), followed by left-sided colon carcinomas (7/4 or 17%) (p
      < 0.05), with 6/14 and 4/7 MMR gene mutations, respectively. The likelihood that
      a tumor would be MSI-positive was 3.3 times greater for right-sided than for left
      sided colon cancer (OR 3.3, p < 0.05). Microsatellite instability was 8.1 times
      more frequent in colon cancers than in rectal cancers (p < 0.05). The presence of
      MSI was independently related to fulfillment of the Bethesda criteria (OR 7.0, p
      = 0.01). In families with multiple cases of colorectal cancer, the rectal cancers
      are only rarely MSI-positive. This indicates that even in families with multiple
      colorectal cancers, rectal cancers are most commonly of sporadic origin.

PMID- 12519375
TI  - A predominant increase in the APC gene isoform with exon 9a in a case of
      attenuated familial adenomatous polyposis.

PMID- 12519376
TI  - PROMM and deafness: exclusion of ZNF9 as the disease gene in DFNA18 suggests a
      polygenic origin of the PROMM/DM2 phenotype.

PMID- 12519377
TI  - A case of de novo distal duplication of chromosome 15.

PMID- 12519378
TI  - 'Severe' Prader-Willi syndrome with a large deletion of chromosome 15 due to an
      unbalanced t(15,22)(q14;q11.2) translocation.

PMID- 12519380
TI  - After chemotherapy, functional humoral response capacity is restored before
      complete restoration of lymphoid compartments.
AB  - Chemotherapy has, besides the beneficial effects, several adverse effects.
      Suppression of the immune system is one of the most important problems.
      Infections caused by encapsulated bacteria like Streptococcus pneumoniae are
      responsible for a major part of infectious problems during and after treatment.
      The splenic marginal zone is essential in the initiation of an immune response to
      encapsulated bacteria. In this study, we analysed the effects of three different
      cytostatic agents on humoral immune responses. We found a reduced, but detectable
      immune response capacity at two days after treatment although the marginal zone B
      cell population is severely reduced at this time point. Twenty-four days after
      cessation of treatment, the immune response capacity was largely restored
      although lymphoid compartments were still not completely restored at that time
      point. Apparently, the presence of only few marginal zone B cells is sufficient
      to evoke a rise in antibody titres and although antibody titre increases are low,
      even small rises are most likely clinically relevant.

PMID- 12519379
TI  - Prospects for immunotherapy of malignant disease.
AB  - The majority of T cell-recognized tumour antigens in humans are encoded by genes
      that are also present in normal tissues. Low levels of gene expression in normal
      cells can lead to the inactivation of high-avidity T cells by immunological
      tolerance mechanisms. As a consequence, low-avidity T cell responses in patients
      are often inadequate in providing tumour protection. Recently, several
      technologies have been developed to overcome tolerance, allowing the isolation of
      high-affinity, HLA-restricted receptors specific for tumour-associated peptide
      epitopes. Furthermore, transfer of HLA-restricted antigen receptors provides an
      opportunity to empower patient T cells with new tumour-reactive specificities
      that cannot be retrieved from the autologous T cell repertoire.

PMID- 12519382
TI  - Vaginal T lymphocyte population kinetics during experimental vaginal candidosis:
      evidence for a possible role of CD8+ T cells in protection against vaginal
      candidosis.
AB  - Vaginal candidosis represents a significant health problem to women of
      childbearing age worldwide. It has been postulated that localized T cells play a
      role in protection against vaginal candidosis. In an attempt to evaluate the role
      of vaginal T cells in protection against vaginal candidosis, T cell population
      kinetics was evaluated using an oestrogen-dependent vaginal candidosis murine
      model. Vaginal T lymphocytes were isolated at different time points post C.
      albicans inoculation, viable cells were enumerated, phenotypically analysed for
      the expression of CD3, CD4 and CD8 T cell markers and absolute numbers of T cell
      subsets were calculated. Oestrogen-induced persistence of vaginal candidosis
      resulted in a significant increase in the total number of vaginal lymphocytes
      within 24-48 h post infection; increased vaginal lymphocyte numbers persisted
      throughout the infection period. The number of CD3+ T cells dramatically
      increased following C. albicans administration and was maintained at high levels
      throughout the infection period. The majority of CD3+ T cells were of the CD8+
      type; however, considerable numbers of both CD4+ T cells and CD4+CD8+ T cells
      were also observed throughout the infection period. The considerable and
      persistent increase in vaginal T cell numbers in general and that of CD8+ T cells
      in particular are evidence of the possible role played by localized T cells in
      protection against vaginal candidosis.

PMID- 12519381
TI  - Development of CD4+ T cell lines that suppress an antigen-specific immune
      response in vivo.
AB  - It has been suggested for many years that the regulation of the immune system for
      the maintenance of peripheral tolerance may involve regulatory/suppressor T
      cells. In the past few years, several investigators have demonstrated that these
      cells can be generated in vitro. It has also been shown that they can inhibit the
      progression of various autoimmune disease models when infused into susceptible
      mice. We have generated two murine T cell lines in the presence of KLH-specific T
      cell clones from BALB/c or DBA2 mice. The lines are characterized by a low
      proliferative response to mitogens, the capacity to secrete high amounts of IL-10
      and TGF-beta, and small amounts of IFN-gamma. Interestingly, these cells are
      unable to produce IL-2, IL-4 or IL-5. The study of the surface phenotype of both
      lines revealed CD4+, CD25high, CD44low and CTLA-4- cells. When injected
      intravenously in (CBy.D2) F1 mice, these cells were able to inhibit 50-100% of
      the TNP-specific antibody production, when the hapten was coupled to KLH. In the
      present study we offer another evidence for the existence of regulatory T cells
      in the T lymphocyte repertoire, suggesting that they can also regulate immune
      responses to foreign antigens. Furthermore, we demonstrate an alternative pathway
      to generate these cells different from approaches used thus far.

PMID- 12519383
TI  - CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit
      proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid
      mice with colitis.
AB  - Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in
      the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina
      propria (LP), express an activated Th1 phenotype and proliferate vigorously when
      exposed ex vivo to enteric bacterial antigens. As LP CD4+ T cells from normal
      BALB/c mice do not respond to enteric bacterial antigens, we have investigated
      whether colonic LP-derived CD4+ T cells from normal mice suppress the
      antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived
      CD4+ T cells cocultured with bone marrow-derived dendritic cells effectively
      suppress the antibacterial proliferative response of CD4+ T cells from scid mice
      with colitis. The majority of these LP T-reg cells display a nonactivated
      phenotype and suppression is independent of antigen exposure, is partly mediated
      by soluble factor(s) different from IL-10 and TGF-beta, and is not prevented by
      the addition of high doses of IL-2 to the assay culture. Functionally and
      phenotypically the T-reg cells of the present study differ from previously
      described subsets of T-reg cells. The presence of T cells with a regulatory
      potential in the normal colonic mucosa suggests a role for these cells in the
      maintenance of local immune homeostasis of the gut.

PMID- 12519384
TI  - Differential CD86 and CD40 co-stimulatory molecules and cytokine expression
      pattern induced by Trypanosoma cruzi in APCs from resistant or susceptible mice.
AB  - Differential aspects of the host immune response generated by Trypanosoma cruzi
      infection were examined in two different mouse strains, BALB/c (haplotype H2-Kd)
      which does not overcome the acute phase of the infection and C57BL/6 (haplotype
      H2-Kb) which survives to the acute phase. After infection an increase in CD3+ T
      cells was observed in both mouse strains in the peritoneal cavity. However, while
      the CD3+ T cells from the BALB/c mice showed an increase in the IL-4 cytokine
      expression level, the same type of cells from the C57BL/6 mice showed an increase
      in IFN-gamma expression. In addition, only the macrophages from the C57BL/6 mice
      were activated secreting IL-12 and TNF-alpha and producing, moreover, high levels
      of nitrites. It was observed that also after parasite infection the expression of
      macrophage and dendritic cells CD40 and CD86 co-stimulation molecules from the
      spleen were diminished in BALB/c but not in C57BL/6 mice. In correlation with
      this observation the macrophages from the spleen of infected BALB/c mice secreted
      lower concentrations of nitrites than the C57BL/6 mouse cells. Also, the spleen
      dendritic cells from infected BALB/c mice had a small potential to present
      alloantigens in contrast to that observed in the infected C57BL/6 mouse cells.

PMID- 12519385
TI  - Nicotinamide is a potent inhibitor of proinflammatory cytokines.
AB  - The present study investigates the modulating effects of nicotinamide on the
      cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole
      blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high
      levels of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha. When
      coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide,
      all four cytokines measured were inhibited in a dose dependent manner. Inhibition
      was observed already at a nicotinamide concentration of 2 mmol/l. At a
      concentration of 40 mmol/l, the IL-1 beta, IL-6 and TNF alpha responses were
      reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin
      stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair
      enzyme. It has been hypothesized that the anti-inflammatory properties of
      nicotinamide are due to PARP inhibition. In the present study, the endotoxin
      induced PARP activation was dose dependently decreased with 4-40 mmol/l
      nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP
      inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory
      cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems
      not to be due to PARP inhibition. In conclusion, the present study could not only
      confirm previous reports of a down-regulatory effect on TNFalpha, but
      demonstrates that nicotinamide is a potent modulator of several proinflammatory
      cytokines. These findings demonstrate that nicotinamide has a potent
      immunomodulatory effect in vitro, and may have great potential for treatment of
      human inflammatory disease.

PMID- 12519386
TI  - Butyrate modulates intestinal epithelial cell-mediated neutrophil migration.
AB  - Butyrate, a short-chain fatty acid released by colonic bacteria and administered
      therapeutically in inflammatory bowel diseases, exerts immunomodulatory
      properties. The aim of the study was to determine the functional consequences of
      butyrate exposure on the proinflammatory responsiveness of human intestinal
      epithelial cells (IEC). IL-8 promoter activity in IEC pretreated with butyrate
      then exposed to proinflammatory stimuli was assayed by transfection of luciferase
      constructs. IL-8 secretion was determined by ELISA and neutrophil migration by
      flow cytometry. Receptor mRNA was assessed by reverse transcriptase-polymerase
      chain reaction (RT-PCR). Butyrate modulated proinflammatory IL-8 secretion
      differentially in Caco-2 and HT-29 cells on the transcriptional level. Pointing
      to the potentially underlying mechanism of increased IL-1 beta-stimulated IL-8
      secretion in HT-29 cells, butyrate up-regulated IL-1RI mRNA but not IL-1RII.
      Butyrate pretreatment of IEC lines stimulated by IL-1 beta modulated neutrophil
      migration significantly: reduction towards Caco-2 and enhancement towards HT-29/p
      cells. Pharmacological inhibition of protein tyrosine phosphatases or treatment
      with mesalamine or sulphasalazine diminished IL-1 beta-stimulated IL-8 secretion
      by butyrate-exposed HT-29 cells substantially. Immunomodulatory effects of
      butyrate on IEC are functionally relevant for neutrophil migration.
      Pharmacological inhibition of enhanced IL-1 beta-mediated IL-8 secretion in a
      subpopulation of IEC may improve the clinical efficacy of butyrate.

PMID- 12519387
TI  - T cell activation by soluble C1q-bearing immune complexes: implications for the
      pathogenesis of rheumatoid arthritis.
AB  - Both innate and adaptive immune systems are thought to participate in the
      pathogenesis of rheumatoid arthritis in adults and children. The experiments
      reported here were undertaken to examine how immune complexes, potent stimulators
      of inflammation, may regulate cells of the adaptive immune system. Human T cells
      were prepared from peripheral blood by negative selection and incubated with
      bovine serum albumin (BSA)-anti-BSA immune complexes that were formed in the
      presence or absence of human C1q. C1q-bearing immune complexes, but not
      unopsonized complexes, elicited both TNF-alpha and IFN-gamma secretion from human
      T cells. Secretion of both cytokines was time- and dose-dependent. Cross-linking
      C1q on the cell surface of T cells produced the same results. Cytokine secretion
      was not inhibited by blocking the C3b receptor (CR1, CD35) on T cells prior to
      incubation with immune complexes. Reverse transcriptase polymerase chain reaction
      (RT-PCR) of immune complex-stimulated cells revealed accumulation of both TNF
      alpha and IFN-gamma mRNA within 2 h post-stimulation. IL-2 was not detected in
      cell culture supernatants, but IL-2 receptor alpha chain (CD25) was detected in
      low density on a small proportion of T cells activated by C1q-bearing immune
      complexes. Secretion of both cytokines was inhibited partially, but not
      completely, by IL-10. These experiments show that immune complexes, potent
      inflammatory mediators, may activate T cells through a novel mechanism. These
      findings have implications for chronic inflammatory diseases in humans.

PMID- 12519388
TI  - Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of
      rheumatoid arthritis.
AB  - The extracellular domain of the T cell co-stimulatory molecule CD26 possesses
      dipeptidyl peptidase IV (DP IV) enzyme activity. Activated T cells are known to
      increase expression of cell surface DP IV and some specific inhibitors of this
      enzyme have been reported to suppress T cell function. Previously we have
      identified a DP IV inhibitor, designated TMC-2, found in culture supernatant of
      Aspergillus oryzae. Administration of TMC-2 to rats with adjuvant arthritis
      caused marked suppression of paw swelling. To elucidate the mechanism of TMC-2
      antiarthritic activity, we have studied its effects on T cell function. Here we
      show that TMC-2 inhibited DP IV activity of CD26 immunoprecipitated from T cell
      lysates, and also inhibited proliferative responses of T cells to specific
      antigen or anti-CD3 antibody. Suppression of IL-2 production was demonstrated at
      both the mRNA and protein levels. TMC-2 did not alter the PTPase activity of pure
      CD45, but when this molecule was co-precipitated from T cell lysates together
      with associated CD26, its PTPase was virtually completely abolished by TMC-2.
      These results suggest that modulation of CD45 PTPase activity might be
      responsible for functional suppression of T cells by TMC-2. Because the effects
      of TMC-2 on T cells were reversible and it was not toxic at the concentrations
      used, TMC-2 may be a candidate novel therapeutic agent for rheumatoid arthritis.

PMID- 12519389
TI  - Regulation of the interleukin-5 receptor alpha-subunit on peripheral blood
      eosinophils from healthy subjects.
AB  - The aim was to study in vitro regulation of the IL-5 receptor alpha (IL-5R alpha)
      on purified peripheral blood eosinophils from healthy subjects. The IL-5R alpha
      was down-regulated, in a dose-dependent manner, by recombinant IL-5 and GM-CSF,
      with IL-5 being most potent. This down-regulation was not induced by autocrine
      release of GM-CSF or IL-5, respectively. Incubation of eosinophils with cell-free
      peritoneal dialysis fluid (PF) collected from a patient with peritoneal fluid
      eosinophilia (PFE), induced up-regulation of the proportion of CD69 positive
      eosinophils, in parallel with down-regulation of the proportion of IL-5R alpha
      positive eosinophils. Experiments with neutralizing antibodies against IL-5 and
      GM-CSF, revealed that IL-5 was the principal cytokine responsible for the down
      regulation of the IL-5R alpha. When eosinophils were incubated with PF collected
      from the same patient in remission or with PF collected from a newly started
      patient or a patient with bacterial peritonitis, less down-regulation of the IL
      5R alpha was observed. In conclusion our data indicate that IL-5, as opposed to
      its proposed action on eosinophil progenitors, down-regulates the IL-5R alpha
      chain on mature eosinophils. We therefore suggest that an IL-5 driven
      inflammation generates an eosinophil tissue phenotype that is characterized by a
      low IL-5R alpha expression. These aspects of IL-5 action on IL-5R alpha
      expression could gain new insights into the mechanisms of specific immuno
      modulatory therapies, such as anti-IL-5.

PMID- 12519390
TI  - In vitro dendritic cell-induced T cell responses to B cell chronic lymphocytic
      leukaemia enhanced by IL-15 and dendritic cell-B-CLL electrofusion hybrids.
AB  - HLA class II-restricted proliferative and cytotoxic T cell (CTL) responses to B
      cell chronic lymphocytic leukaemia (B-CLL) can be generated using autologous
      dendritic cells (DCs) pulsed with tumour cell lysate. In this study a number of
      different approaches were used to optimize further the in vitro system. First,
      the effects of a variety of maturation agents were studied. The addition of TNF
      alpha, polyriboinosinic polyribocytidylic acid (Poly(I:C)) and LPS to autologous
      DCs resulted in the emergence of only a small percentage of CD83+ DCs, IFN-alpha
      having no demonstrable effect. Only the addition of Poly(I:C) to DCs resulted in
      modestly increased specific cytotoxicity to B-CLL targets, IFN-alpha and LPS
      having no effect. Secondly, T cells were pretreated with IL-15, prior to
      culturing with lysate-pulsed autologous DCs. A significant increase in T cell
      activation (P = 0.038), IFN-gamma secretion (P = 0.030) and specific cytotoxicity
      to B-CLL targets (P = 0.006) was demonstrated compared to untreated T cells.
      Thirdly, monocyte derived DCs electrofused with B-CLL B cells were compared with
      lysate-pulsed DCs. T cells stimulated by fused DCs generated higher levels of
      specific cytotoxicity to autologous B-CLL B cell targets than those stimulated by
      lysate pulsed DCs (P = 0.013). Blocking studies demonstrated inhibition of this
      cytotoxicity by both anti-CD4 (P = 0.062) and anti-CD8 monoclonal antibodies (P =
      0.018), suggesting the generation of both HLA class I- and HLA class II
      restricted CTL responses. In summary, in vitro B-CLL-specific T cell responses
      can be enhanced further by preincubating T cells with IL-15 and using autologous
      fused DC-B-CLL hybrids instead of autologous lysate-pulsed DCs. These preliminary
      data require confirmation with larger numbers of patients. Such an approach,
      however, may eventually provide effective immunotherapy for treatment of B-CLL.

PMID- 12519391
TI  - Increased expression of antimicrobial peptides and lysozyme in colonic epithelial
      cells of patients with ulcerative colitis.
AB  - The impact of chronic inflammation on the expression of human alpha-defensins 5
      and 6 (HD-5, HD-6), beta-defensins 1 and 2 (hBD-1, hBD-2) and lysozyme in
      epithelial cells of small and large intestine was investigated. Intestinal
      specimens from 16 patients with ulcerative colitis (UC), 14 patients with Crohn's
      disease (CD) and 40 controls with no history of inflammatory bowel disease were
      studied. mRNA expression levels of the five defence molecules were determined in
      freshly isolated epithelial cells by real-time quantitative RT-PCR. Specific copy
      standards were used allowing comparison between the expression levels of the
      different defensins. HD-5 and lysozyme protein expression was also studied by
      immunohistochemistry. Colonic epithelial cells from patients with UC displayed a
      significant increase of hBD-2, HD-5, HD-6 and lysozyme mRNA as compared to
      epithelial cells in controls. Lysozyme mRNA was expressed at very high average
      copy numbers followed by HD-5, HD-6, hBD-1 and hBD-2 mRNA. HD-5 and lysozyme
      protein was demonstrated in metaplastic Paneth-like cells in UC colon. There was
      no correlation between hBD-2 mRNA levels and HD-5 or HD-6 mRNA levels in colon
      epithelial cells of UC patients. Colonic epithelial cells of Crohn's colitis
      patients showed increased mRNA levels of HD-5 and lysozyme mRNA whereas ileal
      epithelial cells of Crohn's patients with ileo-caecal inflammation did not.
      Chronic inflammation in colon results in induction of hBD-2 and alpha-defensins
      and increased lysozyme expression. hBD-1 expression levels in colon remain
      unchanged in colitis. The high antimicrobial activity of epithelial cells in
      chronic colitis may be a consequence of changes in the epithelial lining,
      permitting adherence of both pathogenic bacteria and commensals directly to the
      epithelial cell surface.

PMID- 12519392
TI  - Definition of the HLA-A2 restricted peptides recognized by human CD8+ effector T
      cells by flow-assisted sorting of the CD8+ CD45RA+ CD28- T cell subpopulation.
AB  - In response to antigenic stimulation, naive MHC-class I restricted and antigen
      specific CD8+ CD45RA+ CD28+ T cells undergo clonal expansion, differentiate into
      CD8+ CD45RO+ memory T cells and convert to CD8+ CD45RA+ CD28- T cells displaying
      potent immune effector functions upon re-encounter with the nominal antigen. We
      show that the effector CD8+ CD45RA+ CD28- T cell subset is expanded in peripheral
      blood lymphocytes (PBL) from patients with human papilloma virus (HPV)+ cervical
      lesions as well as in PBL from patients with pulmonary tuberculosis. Flow
      cytometric cell sorted CD8+ CD45RA+ CD28- and CD8+ CD45RA+ CD28- T cells were
      tested for recognition of HLA-A2 restricted peptides derived either from the
      human papillomavirus (HPV)16-E7 gene product, or from M. tuberculosis antigens.
      Mostly CD8+ CD45+ CD28- T cells define antigen/peptide-specific and MHC
      restricted responses. These data were confirmed in PBL from patients with
      tuberculosis using HLA-A2 tetramer-complexes loaded with a peptide from the M.
      tuberculosis Ag85b antigen by flow cytometry. The sorting of this T cell subset
      enables to determine the fine specificity of CD8+ effector T cells without the
      need for in vitro manipulation.

PMID- 12519393
TI  - Th1 and Th1-inducing cytokines in Salmonella infection.
AB  - Thl and Thl-inducing cytokines and T cell responses were investigated in human
      salmonellosis. Serum IFN-gamma, IL-12 and IL-18 levels were increased
      significantly in patients with salmonellosis. The increase in serum IL-15 and IL
      18 levels was more significant and prolonged in patients with the systemic form
      of salmonellosis than in those with the gastroenteric form. The serum IFN-gamma
      level was correlated significantly with IL-12 and IL18 levels, and the IL-15
      level was correlated significantly with IL-18. Upon stimulation with Salmonella
      in vitro, mononuclear cells from salmonellosis patients produced significantly
      higher amounts of IFN-gamma and IL-12 compared with those from healthy controls.
      Anti-IL-12 moAb or anti-IL18 MoAb significantly inhibited Salmonella-induced IFN
      gamma production in vitro. gamma delta T cells expressed significantly higher
      levels of IFN-gamma mRNA in salmonellosis patients than in healthy controls. The
      results suggest that Th1-inducing cytokines appear to be involved in the in vivo
      response against Salmonella infection, promoting IFN-gamma production by alpha
      beta and gamma delta T cells which plays a protective role against Salmonella.

PMID- 12519394
TI  - Prevalence of non-organ specific autoantibodies in HCV-infected subjects in the
      general population.
AB  - The significance of non-organ specific antibodies (NOSAs) in HCV-related chronic
      hepatitis is largely unclear. In this study we evaluated the prevalence of NOSAs
      in a non-selected population of HCV-infected subjects. One hundred and seventy
      anti-HCV positive and 192 anti-HCV negative sex and age-matched subjects (median
      age 64 years, range 7-91 years, female 68%) enrolled from the general population
      of a small Italian town were evaluated for NOSAs by indirect immunofluorescence
      on rat tissue sections and HEp-2 cells, and by counterimmunoelectrophoresis with
      thymus and spleen extracts as the antigen source. One hundred and sixty-three
      (96%) HCV-infected subjects had normal ALT serum levels and no evidence of liver
      disease. NOSAs were found in 31 out of 170 (18%) anti-HCV positive subjects and
      in 20 out of 192 (10%) controls (P = NS), with similar median titre (1:40) and
      range (1:40 to 1:160). Neither liver/kidney microsomal antibody type 1 nor
      antiactin reactivity were detected. No significant association between NOSAs and
      HCV genotypes was observed. In the general population, HCV-infected subjects and
      healthy controls have a similar prevalence of NOSAs. Without continuous liver
      damage HCV infection is unlikely to induce the appearance of NOSAs.

PMID- 12519395
TI  - Evidence for lack of cross-genotype protection of CD4+ T cell responses during
      chronic hepatitis C virus infection.
AB  - CD4+ T lymphocyte responses are thought to play a major role in control of the
      hepatitis C virus (HCV). Few, however, have been mapped down to the level of
      peptide and HLA restriction. Furthermore, the ability of such T cells to respond
      to viruses which differ in genotype has not been addressed in detail. In most
      cases of persistent infection with HCV, CD4 proliferative responses are weak or
      absent. From a large cohort of persistently infected patients, we identified an
      individual with unusually robust and persistent responses in the face of chronic
      infection. We firstly mapped two peptide epitopes to regions of the nonstructural
      protein NS4 (aa1686-1705 and aa 1746-1765). However, in contrast to the genotype
      1a derived antigens used for mapping, the infecting virus was identified as
      genotype 3a. Strikingly, the patient's CD4 response to these epitopes were
      specific only for the genotype 1a sequence, and did not recognize genotype 3a
      synthetic peptides. Serologic assays indicated that prior exposure to HCV of
      genotype 1 had occurred. This patient therefore maintains strong CD4
      proliferative responses which are genotype specific and not cross-reactive. The
      apparent 'misdirection' of these nonprotective responses has important
      implications for the role of natural and vaccine induced CD4 responses in the
      face of variable viruses.

PMID- 12519396
TI  - Stimulated proliferative responses in vertically HIV-infected children on HAART
      correlate with clinical and immunological markers.
AB  - The objective of the study was to investigate the relationship between various
      CD4+ T cell subsets and the ability of peripheral blood mononuclear cells (PBMC)
      to proliferate to several stimuli in vertically human immunodeficiency virus type
      1 (HIV-1)-infected children. We studied 29 HIV-1-infected children on highly
      active antiretroviral therapy (HAART) (median duration: 12.3 months). T cell
      subsets were determined by flow cytometry. Plasma viral load (VL) was quantified
      using a standardized molecular method. Proliferative responses were evaluated by
      [3H]-thymidine incorporation. Decreased proliferative responses of PBMC to
      pokeweed mitogen (PWM) were found for HIV-1-infected children in Centers for
      Disease Control (CDC) clinical categories B and C when compared to the control
      group (P < 0.05). Similarly, children with < or = 15% CD4+ T cells showed a
      decrease in proliferative responses to PWM (P < 0.01), anti-CD3 + anti-CD28 (P <
      0.01) and phytohaemagglutinin (PHA) (P < 0.05) with respect to the control group
      and to children with CD4+ T cells > or = 25%. Proliferative responses to PWM,
      anti-CD3+, anti-CD28 and PHA had a statistically significant positive correlation
      with CD3+/mm3, CD4+/mm3, % CD4 T cells, CD4/CD8 ratio and the percentage of naive
      T cell subsets (CD4+CD45RO-HLA-DR-, CD4+ CD45RA+ CD62L+, CD4+ CD45RA+), CD4+
      CD62L+ and CD4+ T cells co-expressing CD38+ (CD4+ HLA-DR-CD38+, CD4+ CD38+).
      Moreover, we found a negative correlation between PBMC proliferative responses
      and % CD8 T cells, memory, memory-activated and activated CD4+ T cell subsets.
      Lower proliferative responses to PWM (P < 0.01) and PHA (P < 0.01) were
      associated with higher VL. Our data show that higher proliferative responses to
      PWM, anti-CD3 + anti-CD28 and PHA are associated with both non-activated and
      naive CD4+ T cell subsets in HIV-1-infected children on HAART.

PMID- 12519397
TI  - Lymphocyte and mast cell counts are increased in the nasal mucosa in symptomatic
      natural colds.
AB  - Knowledge of the virus-induced immune response is important in understanding the
      pathophysiology of respiratory virus infections. Data on the cellular immune
      response is still limited and based mainly on experimental studies. Natural colds
      may differ in their pathophysiology from experimentally induced ones. To evaluate
      the inflammatory cell responses in the upper respiratory tract during natural
      colds we counted the number of lymphocytes, mast cells and macrophages in the
      nasal mucosa. Nasal biopsies were taken from 22 adult volunteers during the acute
      (2-4 days of symptoms) and convalescent phases (day 21) of the cold, and the
      numbers of cells were counted with immunohistochemical methods. Viral aetiology
      was identified in 14 (64%) subjects by using viral isolation, antigen detection
      and rhino-polymerase chain reaction assays. The number of T lymphocytes was
      increased in the nasal epithelium and that of T and B lymphocytes and mast cells
      in the subepithelial layer in the acute phase compared to the convalescent phase.
      Intraepithelial T lymphocyte counts were significantly higher in the subjects who
      had a proven viral infection or a finding of pathogenic bacteria in the
      nasopharynx compared to the subjects without such findings (P = 0.005 and P =
      0.04, respectively). Contrary to the earlier experimental studies, we found that
      viruses cause accumulation of T and B lymphocytes and mast cells during the first
      days of a symptomatic naturally acquired respiratory infection.

PMID- 12519398
TI  - Interferon-gamma levels in nasopharyngeal secretions of infants with respiratory
      syncytial virus and other respiratory viral infections.
AB  - Respiratory syncytial virus (RSV) infection, one of the most common causes of
      hospitalization of children in developed countries, has been implicated as a
      cause of asthma. We aimed to characterize the cytokine profile in nasopharyngeal
      aspirates (NPAs) taken from infants during upper respiratory tract infection to
      investigate whether RSV induced a unique immune response as compared with other
      viruses. Additionally, we sought to determine whether this profile was influenced
      by the infants' atopic status. A prospective birth cohort of babies at high risk
      of atopy was recruited. Ratios of a T-helper 1 (Th1) cytokine, interferon gamma
      (IFN-gamma) and a T-helper 2 (Th2)-like cytokine, interleukin-10 (IL-10), in NPAs
      were determined during episodes of respiratory tract infections in the first
      year. The viral aetiology of the respiratory tract infections was determined
      using polymerase chain reaction (PCR), culture and immunofluorescence. Atopic
      status was ascertained at 1 year of age using skin prick tests. Participants were
      recruited antenatally and subsequently followed in the community. Sixty babies
      with one or both parents atopic were enrolled into the study. IFN-gamma : IL-10
      ratios in NPAs during upper respiratory tract infections and their correlation
      with viral aetiology and atopic status were the main outcome measures. The mean
      IFN-gamma : IL-10 ratio was significantly lower (due to lower IFN-gamma) during
      RSV infections than during infections with other viruses (P = 0.035). The
      cytokine ratio, however, did not differ between infants with or without wheeze
      during URTIs (P = 0.44), or between infants who were atopic or non-atopic (P =
      0.49). This study suggests that RSV is associated with lower IFN-gamma production
      in young babies, regardless of their atopic status, compared to upper respiratory
      tract infections where either another virus is detected or where no viral
      identification is made.

PMID- 12519399
TI  - Changes in immune parameters and their correction in human cases of tick-borne
      encephalitis.
AB  - Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system
      diseases in humans. General infection leads to the development of meningitis or
      encephalitis, which is characterized by swelling of the brain due to
      inflammation. Tetracyclines may act locally to moderate inflammation in the CNS.
      In this study, we investigated the potential clinical benefits of administering
      tetracycline hydrochloride to patients hospitalized due to suspected TBEV
      infection presenting with fever and evidence of a recent tick bite. We also
      characterized an acute immune response to TBEV by profiling certain cytokines and
      soluble receptors in Tetracycline-treated and untreated patients. Increased serum
      levels of TNF-alpha, IL-1 alpha and IL-6 were found in all patients at admission.
      Soluble receptors presented in the serum of patients in a magnitude higher levels
      than the corresponding cytokines and were increasing during first weak of
      hospitalization. Levels of IL-10 were also rising during that period. In our
      study tetracycline hydrochloride acted as an immunomodulator, which was able to
      reduce manifestations of inflammation response during TBE course; this action led
      to quicker improvement of symptoms and, consequently, to a faster clinical
      recovery. The positive result of tetracycline hydrochloride treatment was
      accompanied by certain particularities in the dynamics of studied cytokines and
      receptors: the concentrations of IL-6, IL-1 beta, TNF-alpha dropped quicker and
      reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased
      faster and reached higher maximum levels in the tetracycline-treated groups.
      Children had the highest levels of IL-6, which were not neurotoxic.

PMID- 12519401
TI  - Reactive arthritis and serum levels of mannose binding lectin -- lack of
      association.
AB  - The purpose was to evaluate the possible association of serum mannose binding
      lectin (s-MBL) levels on type of triggering microbe, duration of diarrhoea,
      incidence and course of reactive arthritis (ReA) caused by Salmonella, Yersinia
      and Campylobacter. Sixty patients with ReA of 1-228 months duration, 173 patients
      with ReA or uncomplicated enterocolitis caused by Campylobacter, 226 sera from
      patients with elevated antibody levels against Salmonella, Yersinia or
      Campylobacter, and 114 blood donors were tested for s-MBL using ELISA technique,
      both direct mannan binding assay and sandwich ELISA. s-MBL was compared with C
      reactive protein (CRP) levels and with the ability of activating complement C4.
      Among the 114 donors 9% had s-MBL <50 microg/l, 16% had from 50-500 microg/l and
      75% had >500 microg/l. The distribution of s-MBL levels in the three-patient
      groups did not differ significantly from the controls. There were no indications
      that low s-MBL was associated with prolonged duration of arthritis, diarrhoea or
      individual bacterial infections. The two MBL assays were comparable with respect
      to serum concentrations, indicating that the actual circulating MBL was also
      functionally active. s-MBL exhibited acute phase reactant behaviour and
      correlated to CRP level, but only in patients with s-MBL concentrations exceeding
      1000 microg/l. MBL in 10 randomly selected ReA sera were tested for the ability
      to activate complement C4. The results did not differ from those of donor
      controls. This study demonstrates that the distributions of s-MBL levels in serum
      among patients with ReA are not different from donor controls. The course,
      outcome or triggering bacteria are not associated with a particular level of s
      MBL.

PMID- 12519400
TI  - T cell vaccination in multiple sclerosis patients with autologous CSF-derived
      activated T cells: results from a pilot study.
AB  - Myelin-reactive T cells are considered to play an essential role in the
      pathogenesis of multiple sclerosis (MS), an autoimmune disease of the central
      nervous system. We have previously studied the effects of T cell vaccination
      (TCV), a procedure by which MS patients are immunized with attenuated autologous
      myelin basic protein (MBP)-reactive T cell clones. Because several myelin
      antigens are described as potential autoantigens for MS, T cell vaccines
      incorporating a broad panel of antimyelin reactivities may have therapeutic
      effects. Previous reports have shown an accumulation of activated T cells
      recognizing multiple myelin antigens in the cerebrospinal fluid (CSF) of MS
      patients. We conducted a pilot clinical trial of TCV with activated CD4+ T cells
      derived from CSF in five MS patients (four RR, one CP) to study safety,
      feasibility and immune effects of TCV. CSF lymphocytes were cultured in the
      presence of rIL-2 and depleted for CD8 cells. After 5-8 weeks CSF T cell lines
      (TCL) were almost pure TCR alpha beta+CD4+ cells of the Th1/Th0 type. The TCL
      showed reactivity to MBP, MOG and/or PLP as tested by Elispot and had a
      restricted clonality. Three immunizations with irradiated CSF vaccines (10
      million cells) were administered with an interval of 2 months. The vaccinations
      were tolerated well and no toxicity or adverse effects were reported. The data
      from this small open-label study cannot be used to support efficacy. However, all
      patients remained clinically stable or had reduced EDSS with no relapses during
      or after the treatment. Proliferative responses against the CSF vaccine were
      observed in 3/5 patients. Anti-ergotypic responses were observed in all patients.
      Anti-MBP/PLP/MOG reactivities remained low or were reduced in all patients. Based
      on these encouraging results, we recently initiated a double-blind placebo
      controlled trial with 60 MS patients to study the effects of TCV with CSF-derived
      vaccines in early RR MS patients.

PMID- 12519402
TI  - Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and
      HIV-infected patients.
AB  - The acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases
      and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was
      established to measure antiCR1 IgG autoAb. Plasma containing alloAb to
      polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were
      used as positive controls. AntiCR1 Ab was found in 3/90 (3.5%) plasma samples
      from healthy blood donors. The binding of these Ab was not inhibited by high salt
      concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they
      bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted
      the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An
      increased frequency of antiCR1 autoAb was found in patients with SLE (36/78;
      46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P < 0.0001),
      and in patients with anticardiolipin Ab (4/21; 19%, P < 0.01) multiple sclerosis
      (7/50; 14%, P < 0.02), and myeloma (autoAb (8/56; 14%, P < 0.02), but not in
      those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q
      binds to CR1, antiC1q Ab were analysed in the same patients. There was no
      correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels
      of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or
      soluble CR1 in plasma. The binding of antiCR1 autoAb to rCR1 fixed on ELISA
      plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast
      to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb
      recognize mostly CR1 epitope(s) not present on the native molecule, suggesting
      that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb
      might indicate a specific immune response to denatured CR1.

PMID- 12519403
TI  - The role of somatic mutation in determining the affinity of anti-DNA antibodies.
AB  - Combinatorial antibody libraries were constructed from the spleen of a patient
      with concomitant systemic lupus erythematosus and idiopathic thrombocytopenia.
      Following selection of the libraries with DNA, a panel of 15 anti-DNA Fabs was
      isolated. Sequence analysis of these antibodies coupled with measurements of
      their affinities for ss- and dsDNA were used to investigate the role of somatic
      mutation in affinity maturation of the anti-DNA response. Examination of the
      germline genes used by these Fabs supports previous studies that suggest there is
      no restriction of the gene usage in the anti-DNA response. However, data are
      presented indicating that VH3 genes and the A27 V(kappa) paired with the
      J(kappa)1 may be over-expressed in the anti-DNA repertoire. Analysis of the role
      of somatic mutation in increasing affinity for DNA indicates that affinity
      maturation has occurred and suggests that the CDR1 and CDR2 of the heavy chain
      are of importance in this process.

PMID- 12519404
TI  - Increased expression of the secretory leukocyte proteinase inhibitor in Wegener's
      granulomatosis.
AB  - The secretory leucocyte proteinase inhibitor (SLPI) is a low molecular weight,
      tissue-specific inhibitor of proteases, such as elastase and cathepsin G. It is
      the major local protease inhibitor in the upper airways. Proteinase 3, the main
      autoantigen in Wegener's granulomatosis (WG), can degrade SLPI proteolytically.
      In addition, SLPI is sensitive to oxidative inactivation by myeloperoxidase
      generated free oxygen radicals. SLPI also has an antimicrobial capacity that can
      be of interest, as infection is considered to play a role in the pathogenesis of
      WG. This study focuses on SLPI expression in patients suffering from WG,
      something that to our knowledge has not been explored hitherto. Serum samples and
      nasal biopsies were obtained from 12 Swedish WG patients, while buffy coats were
      obtained from 33 American WG patients. SLPI levels in serum were measured by
      means of ELISA and the protein was detected by means of immunohistochemistry in
      nasal biopsies. mRNA expression was studied by means of in situ hybridization on
      nasal biopsies and RT-PCR on leucocytes. IL-6 or ESR were measured as markers of
      inflammatory activity. Cystatin C or creatinine was measured as a marker of renal
      filtration. White blood cell counts were registered. In serum, we found close to
      normal SLPI levels, without any correlation to IL-6. Two patients had greatly
      elevated values, both of them suffering from severe renal engagement. Strong SLPI
      mRNA expression was found in nasal biopsies. RT-PCR on leucocyte mRNA showed
      normal or greatly elevated expression of SLPI mRNA, correlating with disease
      activity. Leukocyte SLPI expression seems to be up-regulated in active WG. Serum
      levels were measured in a small number of patients and were found to be close to
      normal. Lack of correlation to the acute phase response indicates a specific
      regulation. This might be linked to an altered protease/antiprotease balance.
      These findings could indicate that SLPI locally participates in the anti
      inflammatory and perhaps antimicrobial response in WG.

PMID- 12519405
TI  - Pathophysiological roles of arginine vasopressin and aquaporin-2 in impaired
      water excretion.

PMID- 12519406
TI  - Testing for growth hormone deficiency in adults -- how to respond?

PMID- 12519407
TI  - First-line thyroid function tests -- TSH alone is not enough.

PMID- 12519408
TI  - Hyperadiponectinaemia in anorexia nervosa.
AB  - OBJECTIVE: Adiponectin (ApN) is a fat-derived hormone that enhances insulin
      sensitivity, controls body weight, prevents atherosclerosis and negatively
      regulates haematopoiesis and immune functions. In contrast to many proteins
      secreted by adipose tissue, the circulating level of ApN falls in obesity and
      insulin resistance states. The influence of starvation-induced depletion of fat
      stores on ApN concentrations is yet unknown. We therefore investigated plasma ApN
      in anorexia nervosa (AN). PATIENTS AND DESIGN: We measured plasma ApN in 26
      female anorectic patients and examined its relationships to several
      anthropometric or metabolic parameters. Twenty-four age-matched healthy female
      controls (C) were also studied. RESULTS: Body mass index (BMI) and fat mass were
      markedly decreased in AN. However, plasma ApN levels were 30% higher in anorectic
      than in control subjects (P < 0.01), while a reverse pattern was observed for
      leptin concentrations. When normalized for fatness, ApN values almost doubled in
      AN. ApN levels were negatively correlated with BMI and fat mass (P < 0.05 in the
      combined population, AN + C). Insulin sensitivity tended to be 40% higher in AN
      (n = 7) than in C (n = 12) subjects, and plasma ApN levels were positively
      correlated with insulin sensitivity (P < 0.05 in AN + C subgroups). Total and low
      density lipoprotein (LDL)-cholesterol were higher, or tended to be higher, in AN,
      but there were no correlations between plasma ApN and plasma lipids. By contrast,
      ApN was related to the lipid profile, in a manner consistent with its
      antiatherogenic role, in healthy controls [i.e. negatively correlated with
      triglycerides, total and LDL-cholesterol and total/high density lipoprotein (HDL)
      cholesterol; P < 0.05 or less for each parameter]. In a multiple regression
      analysis, BMI and insulin sensitivity in AN were independent determinants for ApN
      levels, explaining up to approximately 80% of the variance in this measure.
      CONCLUSIONS: Plasma adiponectin levels are increased in anorexia nervosa. This
      may, at least in part, be due to the lack of negative feedback exerted by fat
      mass on adiponectin production and/or to enhanced insulin sensitivity. We
      speculate that hyperadiponectinaemia could, in turn, contribute to maintain a
      state of enhanced insulin sensitivity and possibly exacerbate haematological and
      infectious complications of anorexia nervosa.

PMID- 12519409
TI  - Effects of oestrogen-only and oestrogen-progestogen replacement therapy upon
      circulating angiotensin I-converting enzyme activity in postmenopausal women.
AB  - OBJECTIVE: Levels of angiotensin I-converting enzyme (ACE) in blood are
      associated with variation in cardiovascular disease risk. Serum ACE activity in
      women may be reduced by combined oestrogen-progestogen hormone replacement
      therapy (HRT). However, the relative contribution of each hormonal component to
      this observation is uncertain. We investigated ACE activity in two groups of
      healthy postmenopausal women receiving HRT regimens. DESIGN: The first group
      received placebo or oestrogen-only HRT randomly (oral conjugated equine
      oestrogens or transdermal 17 beta-oestradiol). The second group was treated with
      oestrogen-only HRT (oral 17 beta-oestradiol) followed by sequential oestrogen
      progestogen HRT (17 beta-oestradiol and dydrogesterone). MEASUREMENTS: Assay of
      blood for soluble ACE activity before and whilst receiving HRT. RESULTS: In the
      first group, oral conjugated equine oestrogens significantly reduced (P < 0.01)
      ACE activity by 18% on average relative to pretreatment whereas non-significant
      changes of -9% and +7% were seen with transdermal 17 beta-oestradiol or placebo
      treatment, respectively. In the second group oestrogen-only HRT significantly
      reduced (P < 0.001) ACE activity by 15% on average. The reduction during both the
      oestrogen-only and combined phases of sequential treatment was 12% and 19%,
      respectively, compared with pretreatment values (P < 0.01 and P < 0.001). ACE
      activity also differed significantly (P < 0.05) between the two phases of
      sequential treatment. CONCLUSIONS: Both oestrogen-only and oestrogen-progestogen
      HRT may reduce ACE activity in blood. Oestrogen and progestogen may exhibit
      additive effects on blood ACE activity.

PMID- 12519410
TI  - Thyroid peroxidase and thyroglobulin autoantibodies in a large survey of
      populations with mild and moderate iodine deficiency.
AB  - BACKGROUND AND AIMS: Autoimmune thyroiditis is one of the most common autoimmune
      disorders. Autoantibodies against the thyroid gland, with thyroid peroxidase
      antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) as the most common
      autoantibodies, can often be demonstrated in serum in population surveys. In the
      present study we evaluated if TPO-Ab and Tg-Ab tend to develop in parallel or
      whether one or the other may be more prevalent in subsets of the population.
      METHODS: In a cross-sectional comparative study, performed in two areas of
      Denmark with mild and moderate iodine deficiency, 4649 randomly selected subjects
      in age groups between 18 and 65 years were examined. Blood tests were analysed
      for TPO-Ab and Tg-Ab using assays based on the radioimmunoassay (RIA) technique.
      The participants answered questionnaires, were clinically examined and had urine
      samples collected. RESULTS: The overall prevalence rate of thyroid autoantibodies
      (TPO-Ab and/or Tg-Ab) was 18.8%. The prevalence rates of TPO-Ab and Tg-Ab were
      similar (13.1 vs. 13.0%). Both antibodies were more frequent in females than in
      males, and in females the prevalence rates increased with age. In the age group
      60-65 years thyroid antibodies were more frequently measured in sera from
      moderate than from mild iodine-deficient area (P = 0.02), whereas no differences
      were seen in younger subjects. In 38.8% of participants with thyroid
      autoantibodies in serum, both antibodies were present. In sera with both TPO-Ab
      and Tg-Ab present the concentrations of the antibodies were generally higher than
      in sera with only one type of antibody present. CONCLUSION: The prevalence rates
      of TPO-Ab and Tg-Ab were similar in this large population survey. The results
      suggest that TPO-Ab and Tg-Ab predominantly develop due to a general alteration
      in the immune system, whereas specific antigenic mechanisms are probably of less
      importance. However, further studies are needed to clarify the mechanisms
      involved in the development of thyroid autoantibodies.

PMID- 12519411
TI  - Demonstration of human telomerase reverse transcriptase (hTERT) in human
      parathyroid tumours by in situ hybridization with a new oligonucleotide probe.
AB  - BACKGROUND AND OBJECTIVE: Telomerase activity is present in most malignant
      tumours and might provide a mechanism for unlimited replication of neoplastic
      cells. Expression of the gene encoding human telomerase reverse transcriptase
      (hTERT), the telomerase catalytic subunit gene, is associated with telomerase
      activity, and it is overexpressed in most parathyroid carcinomas. We have
      therefore studied hTERT expression in parathyroid tumours. METHODS: In the
      present study, we assayed telomerase activity by the telomeric repeat
      amplification protocol (TRAP) and used in situ hybridization (ISH) to study hTERT
      mRNA expression in four parathyroid metastatic cancers, six adenomas and two
      parathyroid hyperplasia tissue specimens. RESULTS: Telomerase activity was
      detected by the TRAP assay in all of the parathyroid cancers (100%) but in none
      of the eight parathyroid benign lesions. hTERT gene expression was detected in
      the nuclei of the parathyroid cancer cells in all of the lesions (100%) but in
      none of the eight parathyroid benign lesions. CONCLUSIONS: Our results
      demonstrate a correlation between telomerase activity and hTERT gene expression
      measured by ISH (P < 0.001) in parathyroid tumours. We succeeded in very clearly
      and sensitively demonstrating hTERT mRNA in parathyroid tissues by using a new
      probe.

PMID- 12519413
TI  - Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave
      more aggressively than ACTH immunonegative tumours but do not recur more
      frequently.
AB  - OBJECTIVES: Anecdotal reports have suggested that silent corticotroph tumours
      behave in an aggressive fashion; however, clear comparative data with other non
      functioning adenomas (NFAs) are lacking. The aims of the study were, first, to
      review the natural history of those non-functioning pituitary adenomas with
      positive immunoreactivity for ACTH and secondly, to determine whether this
      subgroup behave more aggressively than ACTH immunonegative NFAs by means of
      comparison with existing departmental data. METHODS AND PATIENTS: Twenty-eight
      patients (16 men, mean age 51.3 years) who underwent transsphenoidal surgery in
      Oxford between 1975 and 2001 for clinically non-functioning adenomas where the
      subsequent immunostaining was positive for ACTH were identified from the patient
      database. All patients with silent corticotroph tumours who presented during this
      time period have been included in the analysis; three of the patients have
      subsequently died but none have been lost to follow-up. The mean follow-up period
      was 7.4 years (range 0.5-26.9 years) and the results were compared with
      departmental data for NFAs which were immunonegative for ACTH. None of the
      patients had clinical evidence of Cushing's syndrome. Tumour invasiveness was
      classified according to the modified Hardy criteria (Grade 1 = microadenoma (< 1
      cm), Grade 2 = macroadenoma (> 1 cm) +/- suprasellar extension, Grade 3 = local
      invasion with bony destruction and tumour in sphenoid/cavernous sinus and Grade 4
      = central nervous system (CNS) spread or extracranial spread, i.e. metastatic).
      Tumour recurrence was defined as an increase in tumour size compared with the
      first postoperative scan which was used as a baseline. Visual field defects were
      documented in 79% of the 28 patients at presentation compared to 69% in the non
      functioning population as a whole (P = 0.3). The preoperative imaging in the
      silent corticotroph group (13 CT, 14 MRI and one air encephalogram) revealed 68%
      Grade 2 and 32% Grade 3 adenomas. RESULTS: The recurrence rate in the ACTH
      immunopositive tumours was 32% at a mean of 5.8 years (range 1-16 years) which
      was not significantly different from the 33% recurrence rate previously recorded
      in the ACTH immunonegative tumours (P = 0.9). Two of the patients with silent
      corticotroph adenomas have suffered multiple recurrences; one patient has had
      three operations and two courses of radiotherapy for two episodes of recurrence
      and one patient has had four operations, two courses of radiotherapy and gamma
      knife therapy after three recurrences in total. In contrast, no patient with an
      ACTH immunonegative tumour has required more than one course of treatment for
      tumour regrowth. CONCLUSIONS: This is the first single-centre comparative study
      of a series of clinically silent ACTH immunopositive tumours and has demonstrated
      that although they do not recur more often than ACTH immunonegative tumours, when
      they do regrow they show a more aggressive course. The practical implication of
      this is that there is no evidence for different postoperative imaging and
      radiotherapy protocols for ACTH immunopositive and immunonegative NFAs at initial
      presentation. However, if regrowth of a silent corticotroph tumour does occur
      then very careful monitoring is essential, after further treatment.

PMID- 12519412
TI  - Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase
      activity but does not impair cholesterol efflux.
AB  - OBJECTIVE: Androgens and other drugs that reduce plasma concentrations of high
      density lipoprotein (HDL) cholesterol are often considered to be pro-atherogenic.
      Tibolone lowers HDL-cholesterol by 20% but the clinical significance of this
      effect is unknown. METHODS: In a randomized, double-blind study, 34 women
      received 2.5 mg tibolone daily and 34 women received placebo. Serum
      concentrations of lipids, lipoprotein subclasses and apolipoproteins, together
      with plasma activities of lipid transfer proteins and lipolytic enzymes and the
      capacity of plasma to induce cholesterol efflux from cultured cells, were
      measured. RESULTS: Compared to placebo, tibolone reduced serum concentrations of
      HDL-cholesterol (-14%), HDL phosphatidylcholine (-14%), apolipoprotein (apo)A-I (
      12%), HDL subclasses lipoprotein (Lp)A-I (-20%), HDL-apoE (-16%), pre beta-LpA-I
      (-10%) and alpha-LpA-I (-12%) and increased hepatic lipase activity (+25%) and
      HDL sphingomyelin : phosphatidylcholine ratio (10.5%), but did not alter serum
      concentrations of HDL sphingomyelin, apoA-IV and LpA-I/A-II, lipoprotein lipase,
      the plasma activities of lecithin : cholesterol acyl transferase, cholesteryl
      ester transfer protein, phospholipid transfer protein or the plasma capacity to
      release cholesterol from cultured fibroblasts or Fu5AH hepatocytes. CONCLUSIONS:
      Tibolone lowers HDL-cholesterol in part by increasing hepatic lipase activity.
      Conservation of sphingomyelin and apoA-II in HDL, as well as cholesteryl ester
      transfer protein activity, preserves the capacity of plasma to release
      cholesterol, despite the lower concentrations of HDL-cholesterol. This may have
      important implications for the use of steroid effects on HDL concentrations as
      surrogates for atherosclerosis.

PMID- 12519414
TI  - Comparisons of leptin, incretins and body composition in obese and lean patients
      with hypopituitarism and healthy individuals.
AB  - OBJECTIVE: To identify possible abnormalities specific for obesity in
      hypopituitary patients. STUDY DESIGN: Cross-sectional case-control study.
      MEASUREMENTS AND STUDY SUBJECTS: Body composition (DEXA) and measurements of
      fasting plasma levels of glucose-dependent insulinotropic polypeptide (GIP),
      glucagon-like peptides (GLPs), insulin, C-peptide, glucose, leptin and lipids
      were performed in 25 hypopituitary patients (15 obese, 10 normal weight) and 26
      BMI and age-matched healthy controls (16 obese, 10 normal weight). All
      hypopituitary patients had GH deficiency and received adequate substitution
      therapy on this and other deficient axes (3 +/- 1). RESULTS: Fasting GIP-levels
      were significantly higher in obese hypopituitary patients compared to lean
      hypopituitary patients (P < 0.01), while the fasting concentrations of GLP-1 and
      GLP-2 were comparable between obese and lean hypopituitary patients. The same
      trend was seen in obese healthy controls vs. lean controls. No differences were
      observed in glucose, insulin or C-peptide between the hypopituitary patients and
      the controls. Leptin levels were increased in obese hypopituitary patients
      compared to lean hypopituitary patients when adjusted for gender. At least a 2
      fold higher level of leptin was observed in women compared to men in both patient
      groups and healthy controls. Lean female hypopituitary patients had higher leptin
      levels than matched controls. CONCLUSIONS: Fasting levels of GIP were elevated in
      obese substituted hypopituitary patients, while fasting concentrations of GLPs
      were similar. Obese hypopituitary patients had the same degree of
      hyperinsulinaemia, affected glucose tolerance, dyslipoproteinaemia and central
      obesity as obese healthy controls. Further studies are required to identify the
      possible biochemical reasons for obesity in patients with apparently well
      substituted hypopituitarism.

PMID- 12519415
TI  - Does subclinical hypercortisolism adversely affect the bone mineral density of
      patients with adrenal incidentalomas?
AB  - OBJECTIVE: Subclinical hypercortisolism (SH) is detected increasingly in a
      substantial proportion of patients with incidentally discovered adrenal adenomas.
      The clinical implications of SH are currently unclear. Osteoporosis is a well
      known complication of glucocorticoid excess. So far, the impact of SH on bone
      mineral density (BMD) has been studied in a limited number of reports with
      discordant results. In the present study we evaluated the BMD in a large cohort
      of post-menopausal women with adrenal incidentalomas. : patients and measurements
      Forty-two post-menopausal women with incidentally discovered adrenal masses and
      radiological features highly suggestive of benign adrenal adenomas were
      investigated. All patients underwent a standard low-dose dexamethasone
      suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of
      subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations
      of > 70 nmol/l. According to this criterion patients were subdivided into two
      groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no
      significant difference in age, years since menopause and body mass index between
      these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal
      femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS: Post
      menopausal women with SH (group A) exhibited slightly but significantly lower
      absolute and age-adjusted BMD values compared to group B patients in the femoral
      neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs.
      +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/-
      0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of
      the Ward's triangle were also lower in group A patients but the difference did
      not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P
      = 0.06). There was no difference in the lumbar vertebrae between the two groups
      (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16
      vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range
      was minimal with no significant difference between the two groups. However, the
      frequency of osteopenia in group A was significantly greater than in group B
      patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP)
      levels were significantly lower in group A compared to group B patients (18.6 +/-
      8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding
      parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P
      = 0.72). CONCLUSIONS: In this series, post-menopausal women with subclinical
      hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate
      of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of
      proximal femur. These data demonstrate that the subtle hypercortisolism of
      patients with adrenal incidentalomas may have an adverse effect on the bone mass
      of these patients.

PMID- 12519416
TI  - Leptin measurement in urine in children and its relationship to other growth
      peptides in serum and urine.
AB  - OBJECTIVE: Leptin has been implicated in the interaction between nutrition,
      energy balance and sexual maturation in humans. A non-invasive method of
      measuring leptin would greatly facilitate longitudinal studies of changes in
      leptin in normal children. The aim of this study was to evaluate the use of
      urinary leptin as a surrogate for serum leptin measurements. DESIGN: We have
      modified and validated a serum immunoradiometric assay (IRMA) kit for the
      measurement of leptin in urine, and subsequently investigated the relationship
      between urinary leptin and other growth-related proteins. METHODS: Cross
      sectional study: urinary leptin, measured in the first morning urine voided and
      expressed as ng excreted overnight, and serum concentrations of leptin, IGF-I,
      IGF-II, IGFBP-3 and IGFBP-1 were determined in a cohort of 188 healthy
      schoolchildren aged 5-19 years (88 males, 100 females). Height, weight and
      pubertal status were assessed in all children. Longitudinal study: urinary levels
      of leptin, IGF-I and GH were measured daily in two adults (one male, one female)
      over a period of 6 weeks. RESULTS: The detection limit of this modified assay was
      0.59 ng/L. The intra- and interassay coefficients of variation range was 4-8% and
      4-9%, respectively. The recovery of recombinant leptin added to urine was 98
      108%, and the assay had a recovery rate for serial dilution in the range of 106
      112%. Urinary leptin correlated significantly with serum leptin (r = +0.65, P <
      0.01). Urinary leptin showed similar changes through puberty to those of serum
      leptin, with levels rising in females throughout puberty, whereas in males levels
      peaked at G2/G3 then decreased. BMI SDS was the main determinant of urinary
      leptin, as it was for serum leptin. In the cross-sectional study urinary leptin
      correlated significantly with serum IGF-I (r = +0.41, P = 0.001), IGF-II (r =
      +0.19, P = 0.05), IGFBP-3 (r = +0.29, P = 0.001) and IGFBP-1 (r = -0.25, P =
      0.001). In the adult study, leptin was also detected in urine with similar night
      to-night variability to that found for IGF-I and GH. CONCLUSION: Urinary leptin
      is a valid marker of serum leptin concentrations, and therefore this non-invasive
      assay would be a useful tool for longitudinal assessment of changes in leptin in
      children.

PMID- 12519417
TI  - Long-term outcome and mortality after transsphenoidal adenomectomy for
      acromegaly.
AB  - OBJECTIVE: Acromegaly has long been associated with increased mortality but few
      long-term follow-up data are available in patients treated for this disease. We
      therefore studied a group of 103 patients who underwent transsphenoidal
      adenomectomy for acromegaly between 1970 and 1999 and were followed for one to 30
      years. DESIGN AND PATIENTS: A retrospective chart review was performed on 103
      patients living in the province of Quebec, Canada. Mortality data were obtained
      by hospital charts, contact with the patient's family or death certificates.
      Stringent biochemical criteria were used to define remission (random GH < 2.5
      microg/l, or GH nadir after an oral glucose load is < 1 microg/l and IGF-I within
      the normal range) and patient survival in the group in remission and the group
      with persistent disease were compared to survival of the population of Quebec,
      Canada, using the probabilities of the Poisson distribution. RESULTS: There were
      four deaths in the perioperative period, one of which was directly related to
      surgery. Initial remission was obtained in 82% of microadenomas, 60% of
      macroadenomas and 24% of invasive adenomas. The long-term (> or = 10 years)
      remission rate for surgery alone was 52%. A second transsphenoidal surgery,
      radiation therapy and/or octreotide were used in a subset of patients with
      persistent disease. Long-term remission was obtained in 63% of patients. Five
      (mean age, 64 years) of the 57 patients in remission died; this rate did not
      differ significantly from the mortality rate expected in the general population
      (P = 0.18). Thirteen (mean age, 59.8 years) of the 34 patients with persistent
      disease died; this rate was significantly higher than that expected in the
      general population (P = 0.008). CONCLUSIONS: Our observations confirm that
      uncontrolled acromegaly increases mortality compared to the general population
      and that mortality rates similar to the general population are restored once
      remission is induced.

PMID- 12519418
TI  - Acetylcholine does not play a major role in mediating the endocrine responses to
      ghrelin, a natural ligand of the GH secretagogue receptor, in humans.
AB  - OBJECTIVE: Ghrelin is a 28 amino residue peptide produced predominantly by the
      stomach with substantially lower amounts deriving from other central and
      peripheral tissues. Ghrelin is a natural ligand of the GH secretagogue (GHS)
      receptor (GHS-R) and possesses a potent GH-releasing activity for which the
      acylation in serine 3 is essential. Ghrelin also possesses other endocrine and
      non-endocrine activities reflecting central and peripheral GHS-R distribution and
      stimulates PRL, ACTH and cortisol secretion, has been reported able to induce
      hyperglycaemia and to decrease insulin levels and has orexigenic activity.
      Moreover, ghrelin stimulates gastric motility and acid secretion and its action
      is mediated by acetylcholine which, in turn, is known to play a stimulatory
      influence on GH, ACTH and insulin secretion. SUBJECTS AND METHODS: In order to
      clarify the influence, if any, of acetylcholine on the endocrine activities of
      ghrelin, we studied the effects of cholinergic enhancement by pyridostigmine (PD,
      120 mg p.o. at -60 minutes) and blockade by pirenzepine (PIR, 100 mg p.o. at -60
      minutes) on GH, PRL, cortisol, insulin and glucose responses to human acylated
      ghrelin (1.0 microg/kg i.v. at 0 minutes) in seven normal young volunteers [age
      (mean +/- SEM): 28.3 +/- 3.1 years; BMI: 21.9 +/- 0.9 kg/m2]. In the same
      subjects, the effects of PD and PIR on the GH response to GHRH (1.0 microg/kg
      i.v. at 0 minutes) have also been studied. RESULTS: The administration of ghrelin
      induced a prompt increase in circulating GH levels (hAUC: 5452.4 +/- 904.9
      microg*min/L) which was markedly higher (P < 0.01) than that elicited by GHRH
      (966.9 +/- 20.50 microg*min/L). Ghrelin also induced a significant increase in
      PRL (1273.5 +/- 199.7 microg*min/L) and cortisol levels (15505.1 +/- 796.3
      microg*min/L) and a decrease in insulin levels (Delta hAUC: -198.1 +/- 39.2
      mU*min/L) which was preceded by an increase in plasma glucose levels (8743.8 +/-
      593.0 mg*min/dL). The GH response to GHRH was markedly potentiated by PD (4363.3
      +/- 917.3 microg*min/L; P < 0.01 vs. GHRH alone). In turn, PD did not modify
      either the GH response to ghrelin (6564.2 +/- 1753.5 microg*min/L) or its
      stimulatory effect on PRL and cortisol as well as its effects on insulin and
      glucose levels. The GH response to GHRH was inhibited by PIR (171.5 +/- 34.7
      microg*min/L, P < 0.01 vs. GHRH alone) which, in turn, did not significantly
      modify the GH response to ghrelin (4044.0 +/- 948.8 microg*min/L). PIR also did
      not modify the effects of ghrelin on PRL, cortisol, insulin and glucose levels.
      CONCLUSIONS: The endocrine activities of ghrelin are not affected significantly
      by cholinergic enhancement and muscarinic blockade. Thus, acetylcholine does not
      play a major role in the endocrine actions of ghrelin. Moreover, as the
      cholinergic system influences GH secretion via modulation of somatostatin
      release, the present data agree with the assumption that ghrelin is partially
      refractory to the influence of somatostatin.

PMID- 12519419
TI  - Recombinant human growth hormone treatment in elderly patients undergoing
      elective total hip replacement.
AB  - OBJECTIVE: Measures to prevent postoperative catabolism may be of greatest
      benefit in the elderly because of their reduced lean tissue reserve. We examined
      the effects of recombinant human growth hormone (GH) treatment on body
      composition and physical performance in elderly patients undergoing elective
      total hip replacement. METHODS: We recruited 33 patients (aged 60-82 years)
      scheduled for hip replacement. The study was double-blind and placebo-controlled
      with parallel groups. GH or placebo was administered for 14 weeks preoperatively
      (target GH dose 0.04 U/kg/day) and 4 weeks postoperatively (with dose doubled for
      first 2 weeks postoperatively). Serum IGF-I, body composition, mid-thigh muscle
      cross-sectional area, muscle strength and 4-min walking distance were measured at
      baseline, 2-3 days preoperatively and 4 weeks postoperatively. RESULTS: Mean
      serum IGF-I doubled during GH treatment. Lean body mass increased preoperatively
      by an average of 5.2% (representing 1.8 kg) with GH treatment (P < 0.05 vs.
      placebo), but fell postoperatively by 3% in both groups. Similar changes pre- and
      postoperatively were seen for mid-thigh muscle cross-sectional area, such that
      there was no net loss in the GH group but a fall of more than 10% in the placebo
      group (P < 0.005 vs. GH). There was a trend towards a favourable effect of GH on
      strength in the majority of muscles tested, but this was significant only for the
      abductors of the nonoperated hip (P < 0.02), where there was a 7% increase in
      strength over the whole study compared with a 25% decrease in the placebo group.
      Four-minute walking distance improved postoperatively by a mean of 26.9 m in the
      GH group compared with a 19.5 m reduction in the placebo group (P < 0.05). Dose
      related side-effects were seen in the majority of patients receiving GH.
      CONCLUSIONS: In elderly patients undergoing total hip replacement, preoperative
      GH treatment results in improvements in lean body mass and skeletal muscle mass
      that are sufficient to offset postoperative losses. The treatment may also
      preserve or improve muscle strength and postoperative walking ability.

PMID- 12519420
TI  - A signal peptide mutation of the arginine vasopressin gene in monozygotic twins.
AB  - Familial neurohypophysial diabetes insipidus (FNDI) is a rare autosomal dominant
      syndrome stemming from the absence of arginine vasopressin (AVP). More than
      thirty-five different germline mutations in the arginine vasopressin-neurophysin
      II gene have been reported. These mutations are either in the signal peptide or
      scattered throughout the neurophysin II domain. A missense mutation altering
      alanine at position -1 to either valine or threonine in the signal peptide domain
      has previously been found in ten unrelated families. In the present report,
      Brazilian female monozygotic twins with clinically typical central DI in whom
      biochemical and molecular characterization were carried out are described. Direct
      mutational analysis by sequencing of the vasopressin gene in germline DNA
      revealed a heterozygous missense mutation (G-->A) at nucleotide 279, predicting
      the substitution of alanine by threonine at position -1 of the signal peptide
      moiety. In summary, we present an extremely rare case of familial central
      diabetes insipidus in monozygotic Brazilian twins with a seemingly common
      missense mutation in the AVP gene.

PMID- 12519421
TI  - A survey of dopamine agonist withdrawal policy in UK endocrinologists treating
      patients with prolactinomas.

PMID- 12519423
TI  - Transfusion medicine illustrated. The mesenchymal stem cell revealed.

PMID- 12519424
TI  - In vitro evaluation of stored platelets: is there hope for predicting
      posttransfusion platelet survival and function?

PMID- 12519425
TI  - Attitudes toward blood donation incentives in the United States: implications for
      donor recruitment.
AB  - BACKGROUND: The potential effectiveness of various donation incentive programs
      may vary by demographics, first-time or repeat status, and collection site. STUDY
      DESIGN AND METHODS: Attitudes toward future incentives were obtained from a 1998
      anonymous survey sent to 92,581 US blood donors. Responses (encouraged,
      discouraged, no difference) to incentives were compared within demographic
      groups, donations sites, and between first-time and repeat community whole-blood
      (WB) donors using chi-square tests and logistic regressions adjusted for sample
      design. RESULTS: Incentives most likely to encourage donation return among all
      45,588 WB respondents were blood credits (61%), cholesterol screening (61%), and
      prostate-specific antigen (PSA) screening (73% of men). Younger donors (< or = 25
      years old) were 4 to 5 times more likely to be encouraged to donate if offered
      compensatory incentives (tickets to events, discounts or lottery and/or raffle
      tickets), gifts, or a token of appreciation than were those donors older than 55.
      This age effect influenced positive attitudes toward incentives in first-time
      donors and in donors giving at schools, universities, or military sites. Among
      all donors, up to 7 to 9 percent reported they would be discouraged to return if
      offered compensatory incentives. CONCLUSIONS: Blood credits and cholesterol and
      PSA screening would be well received at all donation sites. Gifts, compensatory
      incentives, and tokens of appreciation appeal more to younger donors. These data
      may allow blood centers to optimize recruitment by tailoring limited incentive
      resources more effectively.

PMID- 12519426
TI  - Lapsed donors: an untapped resource.
AB  - BACKGROUND: There is a clear need for methods to recruit and retain donors
      without compromising blood safety. Although prior studies report lower viral
      prevalence rates in repeat donors than those in first-time donors, it is unknown
      if this relationship holds after a lapse of several years between donations.
      STUDY DESIGN AND METHODS: A total of 6.4 million allogeneic donations collected
      at five US blood centers from 1991 through 1998 were classified by donation
      history (first-time vs. repeat) and by length of time between donations (lapsed
      interval length). The prevalence of HCV, HIV, and HBsAg was compared by donation
      history and lapsed interval length. The relationship between lapsed interval
      length and donor demographics was explored. RESULTS: Repeat donors who delayed
      their return for over 5 years were significantly less likely to test positive for
      a viral infection than were first-time donors. The likelihood of a positive test
      result appeared to increase steadily with lapsed interval length for HCV and
      HBsAg, but not for HIV. Younger, less educated, and nonwhite donors were less
      likely to return than others. CONCLUSIONS: Recruitment of donors who have not
      returned for several years could be an effective way to increase the blood supply
      while preserving blood safety. Understanding the relationship of donor
      demographics to return behavior is important for recruitment efforts.

PMID- 12519427
TI  - The risks and benefits of accepting men who have had sex with men as blood
      donors.
AB  - BACKGROUND: It has been suggested that men who have had sex with men (MSM) should
      become eligible to donate blood if they recently abstained from male-to-male sex.
      STUDY DESIGN AND METHODS: The impact of a 12-month deferral policy for MSM on the
      risk of introducing contaminated units in the blood supply and the benefit of
      obtaining additional donations were estimated. Considered were the prevalence of
      HIV among MSM, the window period of infection, the rate of laboratory testing
      errors, and the occurrence of other system failures. This was compared with the
      risk and benefit that currently results from accepting female donors who have had
      sex with MSM. RESULTS: The revised policy for MSM would potentially result in one
      HIV-contaminated unit for every 136,000 additional donations (95% CI, 1 in 69,000
      to 1 in 268,000), for an overall increase in HIV risk estimated at 8 percent. The
      number of donations would increase by 1.3 percent (95% CI, 0.9%-1.7%). The risk
      benefit ratio of currently accepting female partners of MSM is approximately five
      times lower. CONCLUSION: The risk increment of accepting 12-month abstinent MSM
      would be very small but not zero. From a risk-benefit perspective, the current
      deferral policy for MSM is more efficient compared to an analogous hypothetical
      criterion for female partners of MSM.

PMID- 12519428
TI  - An objective structured clinical examination to evaluate health historian
      competencies.
AB  - BACKGROUND: Post-donation information events in the blood-collection process
      account for the majority of errors reported to the FDA. An eight-station
      objective structured clinical examination (OSCE) based on information reported
      after donation was developed as a competency examination for health historians.
      STUDY DESIGN AND METHODS: The OSCE measured two individual skill components:
      history-taking technique (HXE) and ability to record and interpret a medical
      history (HXI). Donor historians at the Hoxworth Blood Center, University of
      Cincinnati Medical Center, were examined (n = 56). RESULTS: In general, staff
      performance was acceptable, but several areas for improvement were identified. Of
      particular concern were the deferrals associated with the malaria scenarios. The
      overall reliability score was greater than 0.8 for the total OSCE and HXI. Using
      the cut score of 0.9, or 90 percent, 10 subjects would not have passed the exam
      based on the HXE score and one person would not have demonstrated competency
      based on the HXI score. CONCLUSION: An OSCE is a reliable, valid, and practical
      method for assessing continued competency in health historians. This form of
      competency assessment and subsequent retraining may reduce the incidence of
      errors in information reported after donation and should be further studied as a
      suitable national standard for assessing competency.

PMID- 12519429
TI  - Long-term hematologic reconstitution after autologous peripheral blood progenitor
      cell transplantation: a comparison between controlled-rate freezing and
      uncontrolled-rate freezing at 80 degrees C.
AB  - BACKGROUND: The most widely used system for peripheral blood progenitor cell
      (PBPC) cryopreservation is controlled-rate freezing (CRF). Uncontrolled-rate
      freezing (URF) at -80 degrees C has also been used, but its clinical impact has
      not been studied sufficiently yet. STUDY DESIGN AND METHODS: Two groups of
      patients were compared: Group A consisted of 69 patients autotransplanted with
      PBPCs cryopreserved with CRF; Group B consisted of 192 patients autotransplanted
      with PBPCs cryopreserved with URF at -80 degrees C. The same cryoprotectant
      solution and storage system were used. RESULTS: A significant delay of
      hematologic reconstitution (HR) in the URF group was observed for neutrophils
      greater than 0.5 x 10(9) per L and for platelets greater than 20 x 10(9) per L
      and greater than 50 x 10(9) per L; we did not observe any differences in the
      clinical course. The long-term HR was comparable in the two groups, all patients
      showed stable engraftment, and no late graft failures were observed. CONCLUSION:
      Our study confirms that URF is safe and allows sustained long-term engraftment
      without increasing the risks of transplantation, even though the early
      engraftment after URF is slower.

PMID- 12519431
TI  - Comparison of two leukapheresis programs for computerized collection of blood
      progenitor cells on a new cell separator.
AB  - BACKGROUND: Peripheral blood progenitor cells (PBPCs) can be collected on various
      cell separators. Two leukapheresis programs (LP-MNC and LP-PBSC-Lym) were
      evaluated for computerized collection of PBPCs on a new cell separator. STUDY
      DESIGN AND METHODS: Leukapheresis assisted by the LP-MNC or LP-PBSC-Lym software
      was performed for the harvesting of PBPCs in 52 oncology patients after
      chemotherapy plus G-CSF treatment and in 18 healthy subjects after G-CSF
      mobilization alone. RESULTS: A total of 38 components from 33 donors via LP-MNC
      and 43 components from 37 donors via LP-PBSC-Lym were collected with a median of
      one (range, one to two) standard-volume leukapheresis procedures (9.2-13.3 L) per
      donor. There were no significant differences between the two groups concerning
      median counts of WBCs, CD34+ cells, CD34+ cell yields per harvest, and CD34+ cell
      yields of cumulative harvests. The blood cell counts after leukapheresis revealed
      that the LP-MNC resulted in significantly higher platelet loss than LP-PBSC-Lym
      (p = 0.024): 35.9 percent (range, 19.2%-66.1%) versus 29.7 percent (11.6%-52.3%).
      Regarding the CD34+ cell collection efficiency, the LP-MNC program was
      significantly better than the LP-PBSC-Lym program (p < 0.001): 77.5 percent
      (range, 35.5%-98.9%) versus 58.3 percent (range, 20.4%-98.9%). However,
      concentrates collected by the LP-PBSC-Lym program had significantly higher
      percentages of MNCs (p < 0.001) and CD34+ cells (p = 0.028) than harvests with
      the LP-MNC program: 90 percent (range, 69%-99%) versus 70 percent (range, 35%
      98%) and 1.2 percent (range, 0.2%-7.3%) versus 0.7 percent (range, 0.2%-6.0%),
      respectively. No leukapheresis-related serious adverse events were seen, and time
      for hematopoietic engraftment was equivalent to data published in the literature.
      CONCLUSION: The LP-MNC program shows a significantly better CD34+ cell collection
      efficiency than the LP-PBSC-Lym program. However, collections with the LP-MNC
      program result in PBPC components with a lower MNC and CD34+ cell concentrations
      and a higher apheresis-related loss of patient's platelets.

PMID- 12519430
TI  - Phase III randomized study comparing 5 or 10 microg per kg per day of filgrastim
      for mobilization of peripheral blood progenitor cells with chemotherapy, followed
      by intensification and autologous transplantation in patients with nonmyeloid
      malignancies.
AB  - BACKGROUND: It is not known whether increasing the dose of filgrastim after
      mobilizing chemotherapy improves collection of peripheral blood progenitor cells
      (PBPC) and leads to faster hematopoietic engraftment after autologous
      transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter
      trial was carried out in patients with breast cancer, multiple myeloma, and
      lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per
      day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose
      chemotherapy, the components from the first two leukapheresis procedures were
      returned, and all patients received 5 microg per kg day of filgrastim after
      transplantation. RESULTS: A total of 131 patients were randomized, of whom 128
      were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and
      112 were transplanted. Only six patients were not transplanted because of
      insufficient CD34+ cell numbers. The median number of CD34+ cells collected in
      the first two leukapheresis procedures tended to be higher in Group B than in
      Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no
      significant difference in median times to platelet (9 days in both groups) or
      neutrophil (8 days in both groups) engraftment or the number of platelet
      transfusions (three in both groups). A subsequent subgroup analysis separating
      patients transplanted after first- or second-line chemotherapy also showed no
      measurable impact of filgrastim dose on the median CD34+ cell yield or on
      platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with
      chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg
      per kg of filgrastim does not provide additional clinical benefit.

PMID- 12519432
TI  - Expression levels of H-type alpha(1,2)-fucosyltransferase gene and histo-blood
      group ABO gene corresponding to hematopoietic cell differentiation.
AB  - BACKGROUND: The expression of ABO antigens on the surface of RBCs is regulated by
      ABO gene-encoded ABO transferase activity after the formation of the H antigen.
      The molecular mechanisms that control the expression of the ABO blood group
      antigens along with erythroid differentiation are one of the most important
      subjects of study in transfusion science. STUDY DESIGN AND METHODS: FUT1(H), ABO,
      and beta 2-microglobulin mRNA were determined by semiquantitative RT-PCR from 27
      hematopoietic cultured cell lines showing various differentiation stages and cell
      lineages and normal PBMNCs. The expression level of each cell was analyzed with
      computer software (Image, NIH) and was shown as the ratio of ABO mRNA or H mRNA
      to beta 2-microglobulin mRNA. The H antigen was also determined by
      immunocytochemical methods with flow cytometry in some cell lines. RESULTS: The
      highest expression of H mRNA was found in KOPM-28 and HEL cell lines and a lower
      expression was found in the mature cells. In contrast, it was observed that H
      antigen expression began at the level of HEL and PL-21 cells and increased with
      cell maturation. The highest expression of ABO mRNA was found in K-562 and KOPM
      28 cell lines and it decreased along with cell maturation. CONCLUSION: Based on
      these results, it is concluded that the transcription of both H and ABO genes
      starts early in immature peripheral blood progenitor cells but gradually
      decreases during cellular maturation and also that the H antigen maintains a high
      level of expression thereafter. These results may reflect the active synthesis of
      H and ABO antigens in normal hematopoietic peripheral blood progenitor cells.

PMID- 12519433
TI  - Screening for alloantibodies in the serum of patients receiving platelet
      transfusions: a comparison of the ELISA, lymphocytotoxicity, and the indirect
      immunofluorescence method.
AB  - BACKGROUND: For screening of alloimmunization in patients repeatedly receiving
      platelet transfusions, different tests are used, none of which is the standard.
      Here we describe a comparison of four tests most commonly used for detection of
      alloimmunization in a group of nonselected patients receiving platelet
      transfusions. STUDY DESIGN AND METHODS: In 99 patients with hematologic
      malignancies who received platelet transfusions, 192 random serum samples were
      tested in the ELISA, the lymphocytotoxic test (LCT), the lymphocyte
      immunofluorescence test (LIFT), and the platelet immunofluorescence test (PIFT).
      Results of all tests were compared. RESULTS: The results of all tests were
      significantly correlated with each other (p < 0.005). ELISA and LIFT were more
      often positive than LCT and PIFT. ELISA and LIFT showed the best correlation (chi
      square test = 63.7, p < 0.001). CONCLUSION: ELISA, the least time-consuming test,
      detects alloimmunization as often as LIFT and more often than LCT and PIFT.

PMID- 12519434
TI  - Thrombotic microangiopathy in blood and marrow transplant patients receiving
      tacrolimus or cyclosporine A.
AB  - BACKGROUND: Cyclosporine A (CSA) and tacrolimus (FK-506) are both associated with
      thrombotic microangiopathy (TMA) in allogeneic BMT recipients, although it is not
      known which drug is more likely to cause the syndrome. The optimal treatment of
      BMT-associated TMA is also not known. STUDY DESIGN AND METHODS: To estimate the
      risks, predisposing factors, and outcomes of TMA, data were analyzed from two
      cohorts of BMT patients who had received CSA or FK-506 in our institution with
      the same clinical definition for TMA. TMA was diagnosed in 11 of 55 patients
      (CSA, 3 of 24; FK-506, 8 of 31). RESULTS: The daily risk of developing TMA was
      0.12 percent for patients receiving CSA and 0.26 percent for those receiving FK
      506 (p = 0.16, chi-square). Among patients receiving FK-506, sibling donor BMT
      recipients were as likely to develop TMA as matched unrelated donor recipients.
      Serum CSA and FK-506 concentrations were not elevated above the therapeutic range
      in most patients with TMA. The blood urea nitrogen to serum creatinine ratio was
      elevated in patients with TMA. Despite daily plasmapheresis, 9 of 11 patients
      died without resolution of TMA; however, the causes of death were multifactorial,
      including GVHD. Histologic evidence for TMA was absent in 1 patient who died with
      persistent clinical signs attributed to microangiopathy. CONCLUSIONS: In this
      study, a high incidence of TMA was found in patients receiving either CSA or FK
      506 following BMT, with uniform diagnostic criteria and strict monitoring.
      Neither drug showed elevated levels in most patients with TMA. Plasmapheresis was
      unsuccessful in reversing most cases of TMA.

PMID- 12519435
TI  - Human herpesvirus 8 seroprevalence and viral load in healthy adult blood donors.
AB  - BACKGROUND: Human herpesvirus 8 (HHV-8) is widely suspected to be a human tumor
      virus because it is associated with Kaposi's sarcoma and primary effusion B cell
      lymphoma. Report of a case of HHV-8-positive donor blood in the US has led to
      concern for the safety of donor blood from HHV-8-seropositive donors. STUDY
      DESIGN AND METHODS: The findings of HHV-8 seroprevalence and virus load from 100
      randomly selected blood donors from the Houston, Texas, area are reported.
      Serology with serial titration was performed using a highly sensitive indirect
      immunofluorescence assay to lytic and latent HHV-8 antigens. For detection of
      blood-borne virus, buffy-coat DNA was subjected to two ultrasensitive nested PCR
      dot blot assays to HHV-8 orf26 and orf72 regions. RESULTS: At a screening titer
      of 1 in 10, nearly one-quarter (23%; 95% CI, 15-33) of the blood donors are HHV-8
      seropositive with a geometric mean titer of 1 in 53. Seroreactivity to lytic
      antigens (23%) greatly exceeded that to latent antigens (5%). There was a
      significant association between seropositivity and older age (p < 0.02), white
      ethnicity (OR, 3.33; 95% CI, 1.40-7.95) and ABO blood group B (OR, 6.44; 95% CI,
      2.46-16.80). No association with sex or CMV seropositivity was demonstrated. No
      HHV-8 viremia was detected, even though 64 percent of tested donor blood samples
      were EBV DNA positive. CONCLUSIONS: Despite a relatively high HHV-8
      seroprevalence in this cohort of Houston area blood donors, HHV-8 DNA was not
      detected in any sample of donor whole blood using a highly sensitive PCR assay.
      Thus, at least in the southeast Texas region, large-scale screening of blood
      donor units for HHV-8 antibody or DNA seems unwarranted.

PMID- 12519436
TI  - An improved serodiagnostic test for Chagas' disease employing a mixture of
      Trypanosoma cruzi recombinant antigens.
AB  - BACKGROUND: Blood transfusion is one of the most important transmission routes of
      Chagas' disease, a major parasitic infection in Latin America. Therefore,
      screening for antibodies to Trypanosoma cruzi is mandatory in blood banks in
      South America. Most of the commercial serologic tests employ epimastigote
      antigens and show a high number of inconclusive and false-positive results, with
      high economic and social costs. STUDY DESIGN AND METHODS: An ELISA using a
      mixture of three T. cruzi recombinant antigens, B13, 1F8, and H49 (mix-ELISA),
      was evaluated, first with a panel of well-characterized sera from 617 patients
      with Chagas' disease and 277 nonchagasic individuals, living in nine countries of
      South and Central America. Subsequently, the mix-ELISA was evaluated with 451
      samples, from an endemic area of Brazil (Goias), that were rejected from several
      blood banks because they presented discrepant results by two commercially
      available kits (indirect immunofluorescence assay, indirect hemagglutination
      assay, and/or ELISA). RESULTS: The mix-ELISA exhibited 99.7 percent sensitivity
      and 98.6 percent specificity in the first evaluation with the 894 samples. In the
      second evaluation, 451 sera that had discrepant results in the first screening
      for Chagas' disease were further analyzed with the mix-ELISA. Upon consideration
      of the consensus results obtained with the trypomastigote excreted-secreted
      antigens blot test, a confirmatory test for Chagas' disease, the mix-ELISA led to
      a reduction in 99.6 percent in the number of discordant sera. CONCLUSION: The
      combination of three T. cruzi recombinant antigens in a multiantigen immunoassay
      was highly sensitive and specific for Chagas' disease diagnosis. It is proposed
      that it can be applicable in blood bank screening in conjunction with the
      conventional serologic tests.

PMID- 12519437
TI  - Residual WBC subsets in filtered prestorage RBCs.
AB  - BACKGROUND: New-generation RBC filters reduce WBC concentrations by 4 to 5 logs
      and may prevent or decrease transfusion complications such as HLA
      alloimmunization, nonhemolytic febrile reaction, and transfusion-transmitted
      infections. The residual level of WBC subsets may influence efficacy of WBC
      reduction for preventing various complications. This study analyzed subsets of
      residual WBCs in WBC-reduced RBC components prepared for a large, multicenter
      prospective study. STUDY DESIGN AND METHODS: The Viral Activation Transfusion
      Study (VATS) assessed the impact of WBC reduction in HIV-1-infected patients
      undergoing RBC transfusion. WBC-reduced RBC from 11 clinical sites with variable
      filtration practices were sorted into "low,""middle," and "high" groups based on
      residual WBC concentration. Subsets were isolated from units by immunocapture
      (anti-CD4-, anti-CD8-, anti-CD15-, and anti-CD19-coated magnetic beads) and
      quantified by PCR amplification. RESULTS: After validation studies confirming
      test methodology, 105 VATS WBC-reduced RBC samples were analyzed. Concentrations
      of subsets in low and middle residual WBC groups were very low in contrast to
      relatively high concentrations in the high group. Although highly significant
      differences were identified between the middle and high groups for total WBCs and
      all subsets, no single subset predominated. CONCLUSION: These results suggest
      that overall efficacy of WBC filtration correlates with removal of WBC subsets.

PMID- 12519438
TI  - The Dombrock blood group system: a review.

PMID- 12519439
TI  - Causes of fetal anemia in hemolytic disease due to anti-K.

PMID- 12519440
TI  - Acute HCV infection detected in a blood donor by NAT.

PMID- 12519441
TI  - HCV NAT (minipool RT-PCR) and HCV core antigen ELISA.

PMID- 12519443
TI  - Severe hemolytic disease of the fetus following in vitro fertilization with
      anonymously donated oocytes.

PMID- 12519447
TI  - Abstracts of the 24th annual meeting of the Japanese Society of Biological
      Psychiatry. 10-12 April 2002, Saitama, Japan.

PMID- 12519448
TI  - Pathogenesis of schizophrenia: Part I. Symptomatology, cognitive characteristics
      and brain morphology.
AB  - The objective of the present study was to provide a pathophysiological model of
      the development of schizophrenia. The method used was a selective review of
      recent findings, including those in our own department, concerning the clinical
      symptoms, cognitive characteristics and morphological brain changes in
      schizophrenia. A four-syndrome classification was proposed in which 'alienation
      syndrome' is separated from delusion syndrome. Memory organization deficit in
      schizophrenia patients was correlated with reduced activation of the left
      inferior frontal regions. Magnetic resonance imaging and statistical parametric
      mapping analysis revealed that volume reduction in the temporal lobe was seen in
      both schizotypal disorder and schizophrenia patients, but schizophrenia patients
      had additional changes in the medial and dorsolateral frontal regions. In
      conclusion, a temporo-frontal dual pathology of schizophrenia was suggested.

PMID- 12519449
TI  - Pathogenesis of schizophrenia: Part II. Temporo-frontal two-step hypothesis.
AB  - The objective of the present study was to provide a pathophysiological model of
      the development of schizophrenia. The method used was the selective review of
      recent findings, including those of animal models from our own department, to
      clarify the relationship between morphological brain changes and dopamine
      metabolism, and the pathophysiology of schizophrenia. The results showed that
      entorhinal cortex-lesioned animals had increased concentrations of dopamine in
      the amygdala, and methamphetamine-induced dopamine release in the amygdala of
      lesioned rats was significantly enhanced compared with sham-operated rats. These
      results and the morphological findings in schizotypal disorder patients support
      the view that temporal lobe changes may underlie a vulnerability to
      schizophrenia. Latent dysfunction in these regions may become clinically apparent
      as positive psychotic symptoms due to additional frontal lobe changes in
      schizophrenia. For the emergence of positive Schneiderian symptoms, aberrant
      activity of sociality-related circuits, including the amygdala was postulated. In
      conclusion, a temporo-frontal two-step hypothesis for the development of
      schizophrenia was suggested.

PMID- 12519450
TI  - Minor physical anomalies in childhood and adolescent onset schizophrenia.
AB  - A modified version of the Waldrop scale (WS) was used to assess the prevalence of
      minor physical anomalies in schizophrenic patients (n = 71) and healthy controls
      (n = 65). The mean total WS score was 3.32 (SD 1.98) for the schizophrenic
      patients, significantly higher than that for the controls (2.19, SD 1.18). Minor
      physical anomalies were compared between two schizophrenic groups, divided on the
      basis of age at onset, early onset schizophrenia (EOS, onset under age 18 years)
      group and late onset schizophrenia (LOS, onset at or above age 20 years) group.
      The mean total WS score was 3.92 (SD 1.86) in the EOS group, significantly higher
      than the 2.59 (SD 1.79) in the LOS group. Minor physical anomalies are an
      indirect index for early prenatal central nervous system (CNS) maldevelopment;
      the present study indicated association between minor physical anomalies and EOS,
      thus a relationship between early prenatal CNS maldevelopment and EOS. These
      results support the hypothesis that EOS constitutes a subset of schizophrenia in
      which neurodevelopmental damage is largely involved.

PMID- 12519451
TI  - Cenesthopathy in adolescence.
AB  - Psychopathological investigation was conducted on the basis of the clinical
      observation of 23 subjects whose cenesthopathic symptoms began before 30 years of
      age. This illness is called 'adolescent cenesthopathy' based on the specificity
      of this mental condition to the adolescent period. Adolescent cenesthopathy is
      compared to schizophrenia, depersonalization, sensitive delusion of reference and
      other symptoms. Outstanding features of adolescent cenesthopathy are shown from
      the perspective of its difference from schizophrenia in terms of the specific
      characteristics of the symptoms in this disease.

PMID- 12519452
TI  - Tumor necrosis factor-beta gene polymorphism may not be associated with major
      depressive disorder in the Korean population.
AB  - Tumor necrosis factor (TNF)-beta has been implicated in the regulation of immune
      system. Alterations of the immune system in patients with major depressive
      disorder (MDD) have been also proposed to date. The present study was undertaken
      to investigate whether TNF-beta gene polymorphism is associated with MDD in the
      Korean population. Ninety-five patients with MDD who met the criteria of DSM-IV
      and 202 gender- and age-matched unrelated volunteers participated in the study.
      Genotyping for TNF-beta gene was performed by a polymerase chain reaction
      restriction fragment length polymorphism method. The genotype and allele
      distribution in patients with MDD was similar to that of the controls. This study
      suggests that the TNF-beta gene polymorphism does not confer a susceptibility to
      MDD in the Korean population. A larger scaled study to examine different races is
      necessary to determine a role in the pathogenesis of MDD.

PMID- 12519453
TI  - Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes and male alcohol
      use disorders in Khon Kaen, north-east Thailand.
AB  - A case-control study on the relationship between alcohol dehydrogenase-2 (ADH2),
      aldehyde dehydrogenase-2 (ALDH2) and male probable alcohol use disorders (AUD)
      was performed in Khon Kaen, north-east Thailand. One hundred and fifty-three
      paired cases (probable AUD) and controls (non-probable AUD) were sampled from
      villagers aged 18-65 years using the modified Michigan Alcoholism Screening Test 
      Thai version, controls being matched for gender, age (+/- 4 years) and village.
      All of the cases and 86.9% of the controls were current drinkers. The percentage
      of ADH2*1/1 among cases was 47.1%, being significantly larger than the 29.4%
      among controls, and yielding a univariate odds ratio (OR) of 2.421* (95%
      confidence interval (CI) = 1.419-4.132) for developing probable AUD. The
      ALDH2*1/1 proportion among cases, 92.8%, was comparable to the 92.2% among
      controls, yielding a univariate OR of 1.100 (95%CI = 0.757-1.599). Multivariate
      analysis based on a conditional logistic regression model and a hierarchically
      well-formulated model strategy revealed that: (i) the OR of developing probable
      AUD due to 1 g increment of daily ethanol drinking was 1.110* among farmers
      (95%CI = 1.054-1.170); (ii) OR due to 1 g increment of daily ethanol drinking was
      1.329* among non-farmers (95%CI = 1.109-1.593); (iii) OR due to either ADH2*1/1
      or ALDH2*1/1 was insignificant; and (iv) the daily amount of smoking is
      independently associated with probable AUD. The present findings suggest that one
      of the genetic factors that may be related to probable AUD among Thai males
      living in the north-east is the ADH2 gene.

PMID- 12519454
TI  - Clinical features in two cases with musical obsessions who successfully responded
      to clomipramine.
AB  - Clinical features in two cases with musical obsessions are presented to discuss
      phenomenological and psychopharmacological differences from those in patients
      with musical hallucinations. The present patients commonly experienced music as
      an internally generated cognitive product accompanied by full insight into the
      senselessness of the symptoms. They also attempted to suppress the musical
      symptoms or to neutralize them with other thoughts. Thus, despite no covert or
      systematic compulsive behaviors, the musical symptoms of the present cases are
      consistent with the phenomenological nature of obsessive-compulsive disorder
      defined in DSM-IV. In addition, in contrast to previous case reports of musical
      hallucinations, the present patients failed to respond to neuroleptics, but
      showed significant response to an adequate trial of clomipramine. Thus, their
      symptoms appear to be phenomenologically and biologically distinct from musical
      hallucinations, especially those characteristic of schizophrenia.

PMID- 12519455
TI  - Actigraphic assessment of the circadian rest-activity rhythm in elderly patients
      hospitalized in an acute care unit.
AB  - Hospitalization for acute illness is a major risk factor of rest-activity rhythm
      disturbance among elderly subjects. The rest-activity rhythm is disturbed by the
      acute illness, aging and hospital environment. The purpose of this study is to
      assess the rest-activity rhythm and light exposure (using a wrist worn actigraph)
      of 10 patients (mean age 81 years, seven females) admitted on an acute care unit,
      suffering from cardiac, respiratory or renal acute disease. A non-parametric
      method was used to analyze activity data. With an improvement of the underlying
      diseases, the mean relative amplitude of rhythm increased from 0.31 +/- 0.19 for
      the first 5-day period after admission to 0.54 +/- 0.21 for the second period
      before discharge (P < 0.05). The amount of time at night spent above a lighting
      threshold of 50 lux decreased from 31.4 to 12.3 min between the two periods. The
      rhythm of elderly subjects hospitalized in the acute care unit is severely
      altered during the initial period and is progressively resynchronized following
      clinical improvement. Under the acute underlying disease and/or aging,
      environmental conditions (light, noise) should be considered to maintain regular
      rest-activity rhythm.

PMID- 12519456
TI  - Correlation between electroencephalography and heart rate variability during
      sleep.
AB  - It is known that autonomic nervous activities change in correspondence with sleep
      stages. However, the characteristics of continuous fluctuations in nocturnal
      autonomic nerve tone have not been clarified in detail. The study aimed to
      determine the possible correlation between the electroencephalogram (EEG) and
      autonomic nervous activities, and to clarify in detail the nocturnal fluctuations
      in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven
      healthy males were obtained. These EEGs were analyzed by fast Fourier
      transformation algorithm to extract delta, sigma and beta power. Heart rate and
      heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV
      indices of low frequency (LF), high frequency (HF) and LF/HF ratio were
      calculated from the spectral analysis of R-R intervals. The sleep stages were
      manually scored according to Rechtschaffen and Kales' criteria. Low frequency and
      LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and
      were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG
      showed inverse correlations with LF (r = - 0.44, P < 0.001) and LF/HF (r = -
      0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among
      NREM sleep stages. Detailed analysis revealed that correlation was evident from
      the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power
      showed negative correlations with LF and LF/HF, suggesting that sympathetic
      nervous activities continuously fluctuate in accordance with sleep deepening and
      lightening.

PMID- 12519457
TI  - Features of obsessive-compulsive disorder in patients primarily diagnosed with
      schizophrenia.
AB  - We investigated the prevalence of obsessive-compulsive disorder (OCD) among
      patients who were primarily diagnosed with schizophrenia. We investigated the
      differences in the neuropsychiatric features and motor symptoms between patients
      with schizophrenia who did or did not have OCD. Seventy-one subjects with the DSM
      IV diagnosis of schizophrenia were evaluated by the Structured Clinical Interview
      for DSM-IV Axis I Disorders, the Yale-Brown Obsessive-compulsive Scale and the
      Positive and Negative Syndrome Scale. To assess their motor symptoms, the
      Abnormal Involuntary Movements Scale, the Barnes rating scale for drug-induced
      akathisia and the Simpson and Angus extrapyramidal symptoms (EPS) rating scale
      were used. The 13 subjects with OCD (18.3%) had significantly more severe motor
      symptoms than the non-OCD subjects. Patients with schizophrenia who exhibit
      moderate to severe motor symptoms as side-effects of neuroleptics, should be
      examined for OCD comorbidity. Patients who are found to have OCD comorbidity must
      be treated with carefully chosen medications, including serotonin re-uptake
      inhibitors.

PMID- 12519458
TI  - Psychosocial adjustment among pediatric cancer patients and their parents.
AB  - Children with cancer face both physical and psychosocial challenges. However,
      there is not enough empirical evidence in Taiwan regarding how they and their
      families cope with their illness. The purpose of the present study was to explore
      the psychosocial impact of cancer on target children and their families as well
      as the degree of depression experienced by these children. Twenty-four pediatric
      cancer patients, aged 8 through 17 years, completed the Chinese version of
      Children Depression Inventory (CDI). Both these patients and 18 parents completed
      questionnaires about their psychosocial adjustment since the diagnosis of cancer.
      The results showed: (i) patients did not perceive significant changes in their
      psychosocial adjustment, whereas parents indicated significantly lower mood of
      patients and a slight decrease in the number of friends; (ii) both parents and
      siblings showed positive adjustment; and (iii) there was neither significant
      difference on the CDI scores between the pediatric cancer patients and a
      normative group, nor significant relationships between patients' CDI scores and
      demographic characteristics of both patients and their parents, parenting
      attitudes, as well as variables related to the illness. Lastly, the results are
      discussed in terms of issues of methodology and instruments. Possible direction
      for further investigations is suggested.

PMID- 12519459
TI  - A naturalistic study of risperidone treatment in seven affiliated university
      hospitals in Korea.
AB  - This retrospective naturalistic study, conducted on patients with schizophrenia,
      was undertaken to examine the differences in the clinical characteristics of
      subjects who were treated with risperidone, but who were discontinued soon after
      administration, and those who were maintained on the drug for a long-term period.
      Data on 210 of 580 inpatients with schizophrenia who were treated with
      risperidone and whose complete medical records were available, were analyzed.
      Patients maintained on risperidone for at least 2 years were assigned to a 'long
      term maintenance' (LTM) group and those who were discontinued within 6 months of
      risperidone administration were assigned to an 'early drop-out' (ED) group. The
      parameters used for comparisons included the patients' demographic
      characteristics, the presence/absence of physical or psychiatric comorbidities,
      the severity of the psychopathology, the typology of the schizophrenia, the
      nature and subjects' responses to previous antipsychotic treatments (if any) and
      dosages of risperidone treatment. Of the 210 subjects, 67 (31.9%) belonged to the
      ED group, whereas 143 (68.1%) were maintained on risperidone at 2 years. There
      were no significant differences in the demographics, nor in the severity of the
      psychopathology, nor were there significant differences in the starting or
      maximal dosages of risperidone administered between the two groups. Exposure to
      any previous antipsychotic and the longest maintained final dosage of risperidone
      were significantly different in the two groups. We believed that a multicenter
      based retrospective naturalistic study would provide useful information about the
      efficacy and other practical aspects of antipsychotic administration.

PMID- 12519460
TI  - Psychological factors and survival after bone marrow transplantation in patients
      with leukemia.
AB  - Psychological factors may be associated with the outcome of cancer treatment,
      including bone marrow transplantation (BMT). However, studies on the issue have
      provided controversial results. In the present study, effects of mood status on
      the outcome was studied through a follow-up period of 1-3 years as well as in
      shorter periods (3 and 8 months) post-BMT in 72 Japanese patients with leukemia.
      Psychological status was evaluated 2 weeks before BMT using Profile of Mood
      States (POMS). The most major factor abstracted from the POMS subscales (Factor
      1, mainly comprising anxiety, depression, anger, fatigue and confusion) was
      associated with disease-free survival rate at 3 months post-BMT. However, the
      factor most significantly associated with the outcome was gender. Females had
      better outcome than males through the period of 1-3 years as well as at 8 months
      post-BMT. When analyzed by gender, Factor 1 was associated with poor prognosis at
      3 and 8 months in males. In females, however, Factor 1 was not significantly
      associated with the prognosis. The present results suggest an association between
      mood status pre-BMT and prognosis post-BMT in a gender-specific manner.

PMID- 12519461
TI  - Long-, intermediate- and short-acting benzodiazepine effects on human sleep EEG
      spectra.
AB  - The effects of 10 mg haloxazolam (HAX), 4 mg flunitrazepam (FNZ), and 0.5 mg
      triazolam (TRI), each administered for seven consecutive nights were studied in
      the sleep electroencephalograms (EEG) of 17 (six HAX, five FNZ and six TRI)
      healthy male student volunteers. Recordings of C3-A1 EEG data from one baseline
      night, three drug nights (first, fourth and seventh) and two withdrawal nights
      (second and fourth) were analyzed using a fast Fourier transformation method. All
      three drugs induced similar changes in the 0.5 Hz to 40 Hz power spectrum; namely
      (i) higher frequency (including the sigma and beta bands) activity increased and
      lower frequency activity reduced on the drug nights; (ii) the enhancement of
      sigma activity peaked during non-rapid eye movement sleep following the first
      administration and was maintained at high levels on all drug nights; (iii) beta
      activity increased through the night after administration of HAX and FNZ, but not
      TRI, which suggests a blood concentration level dependent increase of beta
      activity; and (iv) only HAX showed a residual effect on the fourth withdrawal
      night. These results indicate that (i) chronic administration of these three
      benzodiazepine derivatives produce similar profiles in sleep EEG spectral
      changes, with some differences depending on their half-lives and doses; (ii) the
      mechanism of sigma enhancement is sensitive to even the initial administration
      night of BDZ; and (iii) frequencies below and above the sigma band are less
      sensitive to BDZ and also show an increase through the night after
      administration, suggesting differences in the mechanisms reflected by these EEG
      frequency bands.

PMID- 12519462
TI  - Psychological distress among evacuees of a volcanic eruption in Japan: A follow
      up study.
AB  - Psychological distress in 248 evacuees from a volcanic eruption was evaluated
      using a 30-item General Health Questionnaire (GHQ-30) at four time points after
      evacuation: 6 months, 12 months, 24 months and 44 months. The proportion of
      evacuees with psychological distress (defined as a GHQ score >/= 8) significantly
      decreased from 66.1% (6 months) to 45.6% (44 months). The GHQ mean score
      significantly improved from 12.6 to 8.9. Investigation of each factor on the GHQ
      showed progressive improvement over time in 'anxiety, tension and insomnia' and
      'anergia and social dysfunction'. However, 'depression' began to improve only
      after 44 months and 'interpersonal dysfunction' started to worsen after 12
      months. The dysfunction in interpersonal relationships continued at 44 months.
      Examination of the relation between GHQ mean scores and age group showed that
      recovery from psychological distress was more difficult in middle-aged and older
      evacuees than in younger evacuees.

PMID- 12519463
TI  - Childhood autism rating scale--Tokyo version for screening pervasive
      developmental disorders.
AB  - To assess the utility of the Childhood Autism Rating Scale - Tokyo Version (CARS
      TV), its total score was compared among 430 children with DSM-IV per subgroup
      (i.e. autistic disorder (AD), childhood disintegrative disorder (CDD), Asperger's
      disorder, and pervasive developmental disorders (PDD) not otherwise specified
      (PDDNOS)). Values of Cronbach's alpha were 0.91 for the PDD group and 0.89 for
      the non-PDD mental retardation (MR) group, and 0.93 for both groups combined. The
      total score was significantly higher in PDD (mean = 30.1, SD = 4.5) than in non
      PDD MR (mean = 22.9, SD = 3.3), t(503) = 13.7, P< 0.0001. The cut-off to
      distinguish PDD from non-PDD MR was 25.5/26, with sensitivity, specificity,
      positive predictive value and negative predictive value of 0.86, 0.83, 0.97 and
      0.50, respectively. The total score differed significantly among the four groups,
      with CDD and AD being significantly higher than both PDDNOS and Asperger's
      disorder, PDDNOS being significantly higher than Asperger's disorder and no
      significant difference between CDD and AD. The cut-off to distinguish AD from
      PDDNOS was 30/30.5, with sensitivity, specificity, positive predictive value and
      negative predictive value of 0.71, 0.75, 0.77 and 0.69, respectively. CARS-TV
      seems to be a useful instrument for differentiating between PDD and non-PDD MR
      and between AD and PDDNOS, although further replication is needed.

PMID- 12519464
TI  - Suicide attempt and self-mutilation among Turkish high school students in
      relation with abuse, neglect and dissociation.
AB  - A questionnaire consisting of items about abuse, neglect, self-mutilation and
      suicide attempt and the Turkish Version of the Dissociative Experiences Scale
      were given to 862 high school students. The rates of suicide attempt and self
      mutilative behaviors were 10.1% and 21.4%, respectively. Abused or neglected
      groups (34.3%) had 7.6-fold higher suicide attempts and 2.7-fold higher self
      mutilation behaviours. The logistic regression model showed that each type of
      trauma and dissociation contributed to suicide attempts and self-mutilation, but
      dissociation was the most powerful. Suicidal and self-destructive adolescents
      should precisely be evaluated for abuse, neglect and dissociation in clinical
      practice.

PMID- 12519465
TI  - Association of low dose trazodone treatment with aggravated angle-closure
      glaucoma.

PMID- 12519466
TI  - Biodiversity of nematode assemblages from the region of the Clarion-Clipperton
      Fracture Zone, an area of commercial mining interest.
AB  - BACKGROUND: The possibility for commercial mining of deep-sea manganese nodules
      is currently under exploration in the abyssal Clarion-Clipperton Fracture Zone.
      Nematodes have potential for biomonitoring of the impact of commercial activity
      but the natural biodiversity is unknown. We investigate the feasibility of
      nematodes as biomonitoring organisms and give information about their natural
      biodiversity. RESULTS: The taxonomic composition (at family to genus level) of
      the nematode fauna in the abyssal Pacific is similar, but not identical to, the
      North Atlantic. Given the immature state of marine nematode taxonomy, it is not
      possible to comment on the commonality or otherwise of species between oceans.
      The between basin differences do not appear to be directly linked to current
      ecological factors. The abyssal Pacific region (including the Fracture Zone)
      could be divided into two biodiversity subregions that conform to variations in
      the linked factors of flux to the benthos and of sedimentary characteristics.
      Richer biodiversity is associated with areas of known phytodetritus input and
      higher organic-carbon flux. Despite high reported sample diversity, estimated
      regional diversity is less than 400 species. CONCLUSION: The estimated regional
      diversity of the CCFZ is a tractable figure for biomonitoring of commercial
      activities in this region using marine nematodes, despite the immature taxonomy
      (i.e. most marine species have not been described) of the group. However,
      nematode ecology is in dire need of further study.

PMID- 12519467
TI  - Effects of nitric oxide inhalation on periodic breathing in awake patients with
      chronic heart disease.
AB  - BACKGROUND: Periodic breathing, an abnormal pattern of respiration consisting of
      alternating hyperpnea and hypopnea, has been recognized in patients with heart
      failure. Although fluctuations in pulmonary blood flow have been considered as a
      possible cause of this type of breathing, its patho-physiological mechanisms are
      not fully understood. In this study, we sought to determine whether inhaled
      nitric oxide (NO), a selective pulmonary vasodilator, attenuates periodic
      breathing. METHODS: Eight cardiac patients who exhibited clear oscillatory
      ventilation while awake (age: 62 +/- 16 years, left ventricular ejection
      fraction: 48 +/- 20%) were enrolled in the study. After breathing room air (RA)
      for 15 min, the subjects inhaled air containing 30 ppm of NO for 15 min.
      Respiratory gas variables including minute ventilation (VE) were measured on a
      breath-by-breath basis throughout the test. RESULTS: There were no differences in
      VE (10.7 +/- 1.5 vs. 11.0 +/- 1.7 l/min) or among any of the other hemodynamic or
      respiratory gas variables studied in the control and NO tests, with the exception
      of the end-tidal CO(2) partial pressure (5.0 +/- 0.4 vs. 4.8 +/- 0.5%; p =
      0.018). The % magnitude of oscillation (i.e., the difference between the peak and
      nadir of oscillating VE, divided by the mean VE) was 40.0 +/- 22.4% in RA and not
      influenced by inhaled NO (43.9 +/- 20.8%, p = 0.57). CONCLUSION: Inhaled NO at a
      concentration of 30 ppm did not attenuate periodic breathing in awake patients
      with mild heart failure.

PMID- 12519468
TI  - Osmometric and water-transporting properties of guinea pig cardiac myocytes.
AB  - To elucidate the mechanism of water flux across heart cell membranes, osmotically
      induced volume changes and sarcolemmal water permeability were evaluated in
      isolated guinea pig ventricular myocytes by videomicroscopic measurements of cell
      surface dimensions. Superfusion with anisosmotic solution (0.5-4 times normal
      osmolality) caused a rapid (lt;3 min to new steady state) and reversible cell
      swelling or shrinkage mainly because of proportional changes in cell width and
      thickness. The van't Hoff relationship between relative cell volume and the
      reciprocal of relative osmolality was linear and predicted an apparent
      osmotically dead space of approximately 35% cell volume. The osmotic water
      permeability coefficient (P(f)) measured from the time course of cell
      swelling/shrinkage was approximately 22 microm.s(-1) at 35 degrees C. Arrhenius
      activation energy (E(a)), a measure of the energy barrier to water flux, was
      approximately 3.8 kcal.mol(-1) between 11 and 35 degrees C; this value is
      equivalent to E(a) for free-water diffusion in bulk solution ( approximately 4
      kcal.mol(-1)). Treatment with 0.1 mM Hg(2+), a sulfhydryl-oxidizing reagent,
      reduced P(f) by approximately 90%, and the sulfhydryl-reducing reagent
      dithiothreitol (10 mM) antagonized the inhibitory action of Hg(2+). E(a) measured
      from Hg(2+)-treated myocytes (12.3 kcal.mol(-1)) was in the range of that for
      diffusional water movement through the lipid bilayers (>10 kcal.mol(-1)).
      Although the observed P(f) is small in magnitude, both the low E(a) and the
      sulfhydryl-related modifications of P(f) are characteristic of channel-mediated
      water transport. These data suggest that water channels form a major conduit for
      water crossing the sarcolemma of guinea-pig heart cells.

PMID- 12519469
TI  - Possible role of nitric oxide on adipocyte lipolysis in exercise-trained rats.
AB  - A possible role of nitric oxide (NO) on adipocyte lipolysis was studied in
      exercise-trained (9 weeks of running) rats. Lipolysis in adipose tissue tended to
      be greater in trained rats than in control rats. A treatment of adipose tissue
      with 5 mM N(G)-nitro-L-arginine methyl ester (L-NAME) showed that basal and
      isoproterenol-stimulated lipolysis were both significantly greater in trained
      rats than in control rats. In contrast, in isolated adipocytes L-NAME had no
      effect on lipolysis in either group of rats, though the lipolysis of isolated
      adipocytes was significantly greater in trained rats than in control rats.
      Training significantly reduced nitrite/nitrate production in adipocytes, but not
      in tissue. On the other hand, training increased the protein expression of
      endothelial nitric oxide synthase (eNOS), but not that of inducible NOS (iNOS) in
      the extracts of tissue homogenates. In tissue homogenates, eNOS activity but not
      iNOS activity was significantly greater in trained rats than in control rats. In
      cellular extracts, training significantly reduced the activities of both NOS's,
      but the mRNA expressions of both NOS's were not different between groups. The NO
      donors, S-nitroso-N-acetyl-penicillamine (SNAP) and 1-propamine, 3-(2-hydroxy-2
      nitroso-1-propyl-hydrazine) (PAPA-NONOate), significantly inhibited adipocyte
      lipolysis in response to isoproterenol in both groups. This inhibitory effect of
      SNAP, but not that of PAPA-NONOate, was greater in the adipocytes of trained rats
      than in those of the control rats. Thus it is possible that NO is involved in the
      regulation of lipolysis and that exercise training enhances the responsiveness of
      adipocytes to extracellular NO with the reduced production of nitrite/nitrate in
      adipocytes because of decreased activities of NOS's. On the other hand, it is
      also possible that exercise increases either the activity or the protein
      expression of eNOS in adipose tissue.

PMID- 12519470
TI  - Human olfactory contrast changes during the menstrual cycle.
AB  - Several lines of studies have reported that olfactory perception is influenced by
      physical and hormonal conditions. In the present study, we investigated changes
      of olfactory perception during the menstrual cycle of the human.
      Cyclopentadecanolide vapor was used and its perception intensity was measured by
      6-point category scale methods. We especially focused on a novel concept termed
      "olfactory contrast" that has been just very recently derived from the patch
      clamp experiment that uses the solitary olfactory receptor cell. The results
      obtained from 18 trials (15 subjects) showed that olfactory contrast was
      significantly enhanced at the ovulatory and/or menstrual phases. It is suggested
      that olfactory contrast, which we defined as a new parameter, provides a useful
      tool in many kinds of studies exploring the olfactory perceived ability.

PMID- 12519471
TI  - Simulation of Ca2+ release from the sarcoplasmic reticulum with three-dimensional
      sarcomere model in cardiac muscle.
AB  - A simulation of some basic features of Ca(2+) release from the sarcoplasmic
      reticulum (SR) in cardiac muscle was made with a model based on the mechanism of
      Ca(2+)-induced Ca(2+)-release. The half-sarcomere modeled as a circular cylinder
      was divided into 20 annular elements in the radial, 50 slices in the axial, and
      125 slices in the azimuthal direction. The cylindrical surface of the sarcomere
      was covered by a layer of the SR. The rate of Ca(2+) release from the terminal
      sac (TS) is proportional to the product of the open probability of the Ca(2+)
      release channel and the difference of [Ca(2+)] between the TS and an element
      facing the TS. Ca(2+) moves from element to element by simple diffusion and is
      taken up by the tubular SR via Ca(2+)-ATPase. Ca(2+) influx (I(ca)) to trigger
      the TS Ca(2+) release was introduced to either a single element facing the TS
      (local I(ca)) or to 20 elements aligned at the level of the Z-line (uniform
      I(ca)). The simulation showed that with both types of I(ca), TS Ca(2+) release is
      smoothly graded over a wide range of I(ca) with the TS moderately loaded with
      Ca(2+). The gain determined by dividing the total amount of TS Ca(2+) release by
      I(ca) was greater with local than with uniform I(ca). Mechanical alternans was
      simulated with both the local and uniform I(ca) with an appropriate rate of
      Ca(2+) replenishment to the TS. A Ca(2+) wave was simulated with a model
      consisting of 8 longitudinally consecutive sarcomeres with TS heavily loaded with
      Ca(2+). Thus the present model accounted for graded TS Ca(2+) release, mechanical
      alternans, and Ca(2+) wave in cardiac muscle at the same time.

PMID- 12519472
TI  - Nonuniformity of sarcomere shortenings in the isolated rat ventricular myocyte.
AB  - By projecting the image of a single ventricular myocyte upon a linear image
      sensor, the striation pattern was analyzed during resting and contracting states.
      During rest, the individual cycle length (ICL) of the striation pattern varied
      from 1.8 to 2.0 microm within a given cell. ICL measured every 2 ms fluctuated
      approximately 0.05 microm around the mean. The variance of temporal fluctuations
      was decreased by chelating the extracellular Ca(2+) and increased by the Ca(2+)
      overload. Blocking the Ca(2+) release channels with 10 micromol/l ryanodine
      reversed this increase. In the power spectral density, an increase in the power
      occurred in the frequency range below 10 Hz. This increase should reflect overall
      kinetics of both intracellular Ca(2+) handling and responses of contractile
      filaments, because the same pattern was observed when spontaneous contractions
      occurred as well as when contractions were evoked by activating the L-type Ca(2+)
      channels. It is suggested that the temporal fluctuations of ICL in the resting
      state are caused by spontaneous Ca(2+) release from ryanodine receptors on the
      sarcoplasmic reticulum. Furthermore, under evoked contractions the shortenings of
      ICL were spatially inhomogeneous. These findings of nonuniform sarcomere
      shortenings are consistent with the temporal and spatial inhomogeneity of Ca(2+)
      transients.

PMID- 12519473
TI  - Effects of stimulating the nucleus basalis of Meynert on blood flow and delayed
      neuronal death following transient ischemia in the rat cerebral cortex.
AB  - An increase in cortical cerebral blood flow (CBF), independent of metabolic
      vasodilation, via the activation of cholinergic neurons originating in the
      nucleus basalis of Meynert (NBM) in the basal forebrain and projecting to the
      widespread cortices was recently demonstrated. In the present study, we aimed to
      clarify whether the increase in CBF following a stimulation of the NBM can
      improve delayed death of the cortical neurons following transient ischemia in
      rats. CBF was measured with a laser Doppler flowmeter, and the delayed neuronal
      death of the cerebral cortex produced by intermittent (every 5 s) occlusions of
      the unilateral common carotid artery for 60 min was measured histologically in
      the cortical hemisphere at 3 different coronal levels (6 microm thickness). In
      control rats without occlusion there were 6000-8000 intact neurons and 9-19
      damaged neurons in the cortical hemisphere at each coronal level. During the
      occlusions, CBF ipsilateral to the occluded artery decreased by 13-32% of the
      preocclusion level. Five days after the occlusions, the numbers of damaged
      neurons were increased to 75-181. Repetitive electrical stimulation was delivered
      to the NBM, ipsilateral to the occluded artery, starting 5 min before the
      occlusions and finishing around the end of them. The increase in CBF induced by
      NBM stimulation prevented the occlusion-induced decrease in CBF in all 3 of the
      cortices. The delayed death of the cortical neurons previously observed after the
      occlusions was scarcely observable in all the cortices when NBM was stimulated.
      The present results suggest that NBM-originating vasodilative activation can
      protect the ischemia-induced delayed death of cortical neurons by preventing a
      blood flow decrease in widespread cortices.

PMID- 12519474
TI  - Expression of GFP-tagged low affinity Na+-dependent glucose transporter in
      Xenopus oocytes and CHO cells.
AB  - A low-affinity and high-capacity Na(+)-dependent glucose transporter (SGLT2) was
      inserted into the expression vector tagging of green fluorescent protein (EGFP).
      The protein expression and glucose transport activity were examined in Xenopus
      oocytes and Chinese hamster ovary (CHO) cells. In Western blotting analysis, EGFP
      tagged SGLT2 protein expressed in both Xenopus oocytes and CHO cells. We also
      observed the EGFP fluorescence in both cells with a confocal laser microscope. To
      determine the function of EGFP-tagged SGLT2, we measured the uptake of [(14)C]
      alpha-methyl glucopyranoside (AMG), a specific substrate for SGLT. The AMG uptake
      was time-dependently increased and inhibited by phloridzin in the EGFP-tagged
      SGLT2-expressing cells. The K(m) value of 1.7 mM for AMG and the IC(50) of 2
      microM for phloridzin consist with the renal low affinity Na(+)-dependent glucose
      transporter. These results indicate that EGFP-tagged SGLT2 protein functionally
      expressed both in Xenopus oocytes and CHO cells, and these models are useful for
      studying the regulatory mechanisms of glucose reabsorption.

PMID- 12519475
TI  - Dependence of effective communication distance and characteristic time on the
      secretion rate in intercellular signaling.
AB  - Effective communication distance and characteristic time are discussed in
      relation to the temporal nonuniformity of the secretion rate in intercellular
      signaling. We demonstrated that these characteristics significantly depend on
      secretion time and the strength of the enhanced secretion rate for human
      cytokines.

PMID- 12519476
TI  - Patient-controlled analgesia pumps and surgical site infections.

PMID- 12519477
TI  - Association between patient-controlled analgesia pump use and postoperative
      surgical site infection in intestinal surgery patients.
AB  - BACKGROUND: Patient-controlled analgesia (PCA) pumps are widely used after
      surgery, but their association with various outcomes is not completely
      understood. Is PCA pump use related to the incidence of postoperative surgical
      site infections among patients undergoing open intestinal surgery? MATERIALS AND
      METHODS: We undertook a comprehensive retrospective chart review of 515 randomly
      selected patients over age 18 who had major rectal or intestinal surgery
      (Diagnosis Related Groups [DRGs] 146-149) between January 1994 and March 1997
      from eight community or teaching hospitals along the U.S. west coast. Of these
      patients, 214 used PCA pumps. Outcome measures were in-hospital postoperative
      surgical site infections, respiratory complications, ileus/abdominal distention,
      urinary tract infection/urinary retention, and length of stay. RESULTS: Use of a
      PCA pump was significantly associated with increased in-hospital postoperative
      surgical site infections (10.7% for PCA, 4.0% for no PCA). The odds ratio for PCA
      use was about 4.0 after controlling for many variables, including severity of
      illness at admission, body mass index, preadmission use of corticosteroids,
      perforated viscus, number of previous abdominal operations, wound classification
      category, hypothermia, malnutrition on admission, preoperative antibiotic use
      within 2 h before incision, time from hospital admission to surgery, skin prep to
      incision time, anesthesia start to incision time, surgical skin to skin time,
      wound closure type, time from incision closure to the start of PCA, use of
      drains, blood product use, central line use, line infection, mobility assistance
      required, hospital, DRG, and surgeon. CONCLUSION: No confounding variables
      explained the significant association between PCA pump use and in-hospital
      surgical site infection. These results stand firmly on data that merit additional
      study to further elucidate possible immunologic effects of PCA pumps.

PMID- 12519478
TI  - Insulin-like growth factor binding protein-3 is upregulated in LPS-treated THP-1
      cells.
AB  - BACKGROUND: Lipopolysaccharide (LPS) is a potent activator of human monocytic
      cells. We have determined that LPS stimulation of the human monocytic cell line,
      THP-1, results in an increased apoptotic rate. We hypothesized that cDNA
      expression array analysis could be used to identify target genes involved in the
      regulation of this process. METHODS: THP-1 cells (1 x 10(6)/mL) were stimulated
      with LPS (1 microg/mL) or vehicle control. Apoptosis was measured at 0, 24, 48,
      72 and 96 h using propidium iodide staining and flow cytometry to determine the
      percentage of cells with hypodiploid DNA. At 16 h, the Atlas Human cDNA
      expression array system, containing probes for 205 genes related to apoptosis,
      was used to survey and quantify transcript expression. The experiment was
      performed in duplicate and the membranes were normalized to cytoplasmic beta
      actin. Standard Western blotting was performed on the conditioned medium to
      correlate secreted protein expression with RNA expression. Pretreatment with
      insulin-like growth factor I (IGF-I) was performed to determine whether the
      effects of insulin-like growth factor binding protein-3 (IGFBP-3) on apoptosis
      were IGF-dependent. RESULTS: LPS stimulation of THP-1 cells resulted in a greater
      than 2-fold increase in the rate of apoptosis when compared to vehicle control.
      When the cDNA expression arrays were compared, there was a 500-fold increase in
      the expression of the IGFBP-3 transcript in the LPS-stimulated cells. Western
      blotting of culture medium verified an approximately 2-fold increase in secreted
      IGFBP-3. Pretreatment with IGF-I did not prevent the increase in apoptosis seen
      with LPS stimulation. CONCLUSIONS: THP-1 cell apoptosis is increased in response
      to LPS stimulation and is associated with a significant induction of IGFBP-3 mRNA
      and protein. IGFBP-3, which reportedly promotes apoptosis and modulates the
      bioavailability of the pro-survival insulin-like growth factor 1, may serve to
      regulate apoptosis in monocytic cells in an IGF-independent manner. These data
      further support the investigation of the role of the IGF axis in programmed cell
      death of immune cells.

PMID- 12519479
TI  - Association of leukocyte-depleted blood transfusions with infectious
      complications after cardiac surgery.
AB  - BACKGROUND: To test the hypothesis that leukocyte-mediated immunosuppression may
      contribute to postoperative infections after blood transfusions, we compared the
      incidence of postoperative infections in patients undergoing elective coronary
      artery bypass graft (CABG) surgery who received either leukocyte-depleted (LD
      RBCC) or non-LD transfusions of red blood cell concentrates (RBCC) within 48 h of
      surgery. MATERIALS AND METHODS: Data for all primary elective CABG patients
      between 1995 and 1998 who received allogeneic RBCC transfusions in the first 48 h
      after surgery were collected. Patients were divided into two groups (group LD: LD
      RBCC transfusions only; group non-LD: non-LD-RBCC transfusions only were
      excluded). Patients who received a combination of LD and non-LD-RBCC
      transfusions, or any blood products other than RBCC were excluded. Infectious
      complications recorded included pneumonia, acute respiratory distress syndrome,
      mediastinitis, leg wound/sternal wound infection, nosocomial infection, catheter
      related infection, urinary tract infection, decubitus ulcers, and
      bacteremia/fungemia. RESULTS: One hundred forty-two patients received only LD
      RBCC transfusions, and 1,765 patients received only non-LD-RBCC transfusions.
      Power analysis demonstrated that the sample size attained 80% power to detect an
      odds ratio of 2.1 at a significance level of p < 0.05. Infection rates were not
      significantly different between the non-LD and LD groups (7.57% vs. 9.52%, p =
      0.40). Leukocyte depletion status of RBCC transfusions was not a predictor of
      infectious complications (p = 0.73). However, total units of RBCC received was
      highly associated with increased infection (p = 0.0001). CONCLUSIONS: No
      association between postoperative infections and the use of leukocyte-depleted
      blood was identified. However, an increased incidence of postoperative infections
      was observed to be associated with blood transfusions in general.

PMID- 12519480
TI  - Emergence of resistant microbes in critical care units is transient, despite an
      unrestricted formulary and multiple antibiotic trials.
AB  - BACKGROUND: Antimicrobial resistance is a growing problem in the intensive care
      setting. This study was designed to evaluate the trends in bacterial prevalence
      and changes in antibiotic resistance at a large university hospital over the past
      decade. Antimicrobial resistance data were compared among the surgical intensive
      care unit (SICU), medical intensive care unit (MICU), and burn unit (BNU).
      MATERIALS AND METHODS: A large database was created using hospital-wide data from
      1989 to 2000. A retrospective analysis of the evolution of organism prevalence,
      antibiotic resistance, and response to study protocols was evaluated. The
      formulary was relatively unrestricted. All positive cultures were examined,
      focusing on wound, blood, and sputum cultures. Six primary antibiotics were
      targeted specifically to follow resistance patterns. RESULTS: There were 847
      identified positive wound cultures, 2,862 positive sputum cultures, and 2,252
      positive blood cultures. The incidence of gram-positive and gram-negative
      organisms changed little in the SICU and BNU; however, there was a large increase
      in gram-positive organisms and yeast in the MICU over the past 5 years. Anaerobic
      bacteria and yeast were nearly nonexistent pathogens in the SICU and BNU. The
      resistance pattern of most organisms changed little following the introduction of
      a new antibiotic. However, the effectiveness of study antibiotics after formal
      clinical study periods decreased dramatically, albeit transiently. CONCLUSION:
      Hospital-wide antibiotic resistance data may be misleading and may not reflect
      individual critical care units throughout the hospital. Bacterial flora,
      including resistant organisms, changed little over 10 years, despite an
      unrestricted formulary. The emergence of resistant and opportunistic organisms is
      related to antibiotic usage and can vary significantly over time. This suggests
      that a policy of administering limited duration, narrow spectrum antibiotics may
      reduce drug resistance.

PMID- 12519481
TI  - Omega-3 fatty acid lipid emulsion reduces LPS-stimulated macrophage TNF-alpha
      production.
AB  - BACKGROUND: Omega-3 (omega-3) fatty acids (FA), specifically eicosapentaenoic
      acid (EPA), attenuate cytokine-mediated inflammation. Currently, in the United
      States, there is no commercial source of omega-3 lipid for clinical use. A
      clinically used European lipid emulsion, Omegaven, has been shown to have
      beneficial antiinflammatory effects; however, the mechanisms of its action are
      not well defined. In the present work, this omega-3 FA emulsion has been
      evaluated in order to define its effects on TNF-alpha production in a model of
      LPS-stimulated macrophages. MATERIALS AND METHODS: RAW 264.7 cells (1 x 10(6)
      cell/well) were incubated with DMEM, Omegaven, or an isoenergetic omega-6 lipid
      emulsion, Lipovenos for 4 h. Cells were washed and then stimulated with LPS (1
      microg/mL) or media alone for 3 h. Plate well supernatants were collected and
      assayed for TNF-alpha production by ELISA. Statistical analysis was performed by
      ANOVA and post-hoc analyses; the significance was defined as p < 0.05. RESULTS:
      Unstimulated RAW cell TNF-alpha production was similar in all groups and < 60
      pg/mL. Lipovenos pretreatment did not alter TNF-alpha production from that of
      baseline compared to LPS-stimulated cells. Four-hour Omegaven pretreatment
      significantly reduced TNF-alpha production in LPS-stimulated cells, with a 46%
      reduction in TNF-alpha from baseline observed. CONCLUSION: Four-hour omega-3 FA
      emulsion pretreatment significantly attenuated LPS-stimulated macrophage TNF
      alpha production. These data support the contention that antiinflammatory effects
      of omega-3 FA occur at least in part through the inhibition of macrophage TNF
      alpha production in response to endotoxin. Further studies to define the
      antiinflammatory mechanisms of omega-3 FA on macrophages are warranted. The
      availability of Omegaven as an experimental treatment and Lipovenos as an
      equivalent control will be useful for future studies.

PMID- 12519482
TI  - Down-regulated circulating PMN function after injury despite enhanced p38 MAPK
      activity.
AB  - BACKGROUND: Neutrophils (PMN) are initially primed by injury. However, remaining
      PMN found in the circulation postinjury demonstrate a down-regulated phenotype
      with inhibited apoptosis, CXCR2 expression, and endotoxin (LPS) responsiveness
      that may contribute to infectious complications and organ dysfunction. The p38
      mitogen activated protein kinase (MAPK) signal transduction pathway has been
      implicated in regulating each of these PMN functions. We, therefore, hypothesize
      that p38 signaling is similarly down-regulated in postinjury circulating PMN.
      MATERIALS AND METHODS: PMN were isolated from trauma patients (ISS > 20,
      postinjury day 3) and concurrently from healthy volunteers (control). PMN were
      cultured with LPS (100 ng/mL) and p38 activity assessed by Western blotting of
      cell lysates using a dual phosphospecific antibody for phosphorylated, active
      p38. In separate experiments, PMN from healthy volunteers were cultured in plasma
      from either healthy or injured subjects +/- LPS and p38 activity assessed by a
      cell-free in vitro kinase assay using the transcription factor, ATF-2, as a
      substrate. Apoptosis and IL-1beta secretion of the cultured PMN from each
      experimental condition were also quantified. RESULTS: Circulating PMN from trauma
      patients have an upregulated LPS signaled p38 MAPK response (threefold) compared
      to PMN from healthy volunteers (p < 0.05). Furthermore, circulating factors
      present in trauma plasma can transfer this response to normal PMN. There was no
      significant alteration in apoptosis following LPS treatment between control and
      trauma patient's PMN (control: 62 +/- 3% vs. trauma: 55 +/- 5%), but there was
      decreased secretion of IL-1beta (control: 100 +/- 28 pg/mL vs. trauma: 12 +/- 5
      pg/mL, p < 0.05). CONCLUSION: We conclude that injury down-regulates selective
      PMN function despite enhanced p38 activity. These results suggest a shift in the
      role of PMN p38 signal transduction following injury with additional critical
      regulation of LPS responses downstream to p38 MAPK activity.

PMID- 12519484
TI  - The unfolding illness trajectory of stroke.
AB  - PURPOSE: To describe the characteristics of the illness trajectory of stroke
      during the first year. METHOD: A qualitative, prospective case study design;
      repeated in-depth semi-structured interviews with nine mild to moderately
      affected stroke patients during the course of the first year. A total of 63
      interviews were conducted. The interview data were transcribed verbatim and
      analysed as a text, using a hermeneutic approach. RESULTS: A stroke is not
      necessarily experienced as an abrupt psychosocial crisis by the stroke patient.
      The adjustment process seems to be gradually evolving and prolonged over most of
      the first year following the cerebro-vascular accident (CVA). The illness
      trajectory may be divided into four phases, each with characteristic tasks and
      focal points. The adjustment process involves hard physical and psychosocial work
      on the part of patient. A necessary pre-requisite for adjustment is a realistic
      conception of the illness and its implications. This takes time and experience to
      achieve. CONCLUSIONS: The adjustment process following stroke is gradual and
      prolonged. In order to move away from the predominant functional rehabilitation
      approach towards a more comprehensive and better targeted service, increased
      understanding of the complexities of the adjustment process is necessary.

PMID- 12519483
TI  - The nature of the effects of stroke on trunk flexor and extensor muscles during
      work and at rest.
AB  - PURPOSE: To investigate the nature of stroke induced functional disturbances of
      rectus abdominis and erector spinae in their postural and dynamic roles and
      compare the performances of stroke and neurologically unimpaired groups. METHODS:
      EMG activity was recorded from rectus abdominis and erector spinae during five
      rest/work cycles in forward and backward of vertical positions and during
      reaching and shoe donning. Repeated measures ANOVA was used to compare within and
      between group EMG activity to determine the significance of differences between
      paretic and non-paretic muscles of the stroke group and matched muscles of the
      control group in the two postures and dynamic tasks. RESULTS: In the stroke group
      rectus abdominis responded normally in most instances, demonstrating weakness
      only during shoe donning. This weakness was particularly noticeable on the
      paretic side. Erector spinae activity of the stroke group was significantly
      higher than the controls during all postural and dynamic work and at rest after
      most tasks particularly on the paretic side. CONCLUSION: Findings indicated that
      stroke appears to induce increased activity in erector spinae on both sides
      during postural and dynamic roles and at subsequent rest. By contrast, rectus
      abdominis performed reasonably normally after stroke with weakness noted only
      during dynamic postural support of shoe donning. Explanations for these
      differences might depend on the extent to which cortical influences to muscles
      are disrupted by stroke. Generous contributions from the intact hemisphere might
      enable more normal activity in rectus abdominis, whereas, the abnormal responses
      of erector spinae might reflect a more severe disruption of cortical influences
      on motor unit activity.

PMID- 12519485
TI  - Impact of comprehensive gynecologic services on health maintenance behaviours
      among women with spinal cord injury.
AB  - PURPOSE: Women with spinal cord injury (SCI) and other physical disabilities
      often lack access to appropriate gynecologic health care and may be at higher
      risk for preventable gynecologic diseases and other health problems. The purpose
      of this study was to investigate the effects of a women's health clinic that was
      established to meet the needs of women with SCI and other disabilities.
      Specifically, this study examined the effect of clinic participation upon the
      rate of preventive gynecologic health care behaviours and assessed the
      relationship between physical and emotional functioning in women with SCI and
      other disabilities. METHOD: Participants (n =28) were women who completed surveys
      immediately prior to participation in the clinic, and at 3 and 12 month follow
      ups. RESULTS: Results indicated a trend towards increased frequency of breast
      self-exam three months after initial participation in the clinic (p =0.11). Other
      rates of health promoting behaviours (exercise, diet and mammography) did not
      increase. Results also indicated that although physical functioning and life
      satisfaction were not related, women in this study did experience moderate to
      high levels of psychological distress. CONCLUSION: Results indicate that whole
      woman health care may be important to increasing certain health behaviours among
      women with disabilities. Implications for comprehensive treatment are discussed.

PMID- 12519486
TI  - Audiometric configurations of hearing impaired children in Hong Kong:
      implications for amplification.
AB  - PURPOSE: Children with hearing loss who require special school placement may have
      a wide range of audiometric configurations. Since such children will vary in
      auditory status their amplification requirements may also be diverse. This study
      examined the audiological records of 231 children attending four schools for
      hearing impaired children in Hong Kong to gain an understanding of common
      audiometric patterns found in the school children and their auditory
      rehabilitation needs. METHOD: Data on the children's aetiology of hearing loss,
      hearing status, tympanometric findings and the electroacoustic characteristics of
      their hearing aids were obtained. For 424 children's ears considered having
      essentially sensorineural hearing loss, k-means cluster analysis methods were
      used to categorize audiometric configuration groups. RESULTS: Cluster analysis
      that indicated that five distinct audiometric configurations could be found among
      the school children. Different clusters contained children who had differing
      amplification needs. The study analysed a number of parameters to check fitting
      outcomes, including average prescribed gain, frequency-specific measured versus
      prescribed gain, prescribed frequency response, measured versus prescribed
      frequency response and the predicted aided thresholds for the children.
      CONCLUSION: The amplification needs associated with these five configurations,
      including recommended prescription gain, maximum power output and possible signal
      processing strategies, were considered. The clustering algorithm approach proved
      useful as a means of grouping distinctive audiometric profiles.

PMID- 12519487
TI  - University students with learning disabilities advocating for change.
AB  - PURPOSE: In recent decades Western psychology has conceptualized learning
      disabilities (LD) in terms of deficits and such related 'social emotional issues'
      as insecurity, low self-esteem and social isolation that can be rehabilitated
      through combined remedial teaching and psychological intervention. With
      increasing advocacy and legislation on behalf of people with disabilities in the
      US, UK and Australia, more resources are being made available to students with LD
      in institutions of higher education. Due to this increase in the quantity of
      services, written programmes and accommodations made to their needs, increased
      numbers of students with LD have been graduating successfully from institutions
      of higher education. This paper describes an option for treating students with LD
      that is based on a theoretical perspective that understands these students as an
      excluded population and emphasizes the importance of their empowerment. METHOD: A
      project involving social work students with LD at Hebrew University in Jerusalem
      is presented as a case study. Case-study investigation, one of the common methods
      of qualitative research, explores social and human problems in their natural
      context. A 6-year evaluation of this project was conducted based on
      questionnaires, focus groups, documentation of all activities related to the
      project, in-depth interviews and outcome measures. RESULTS: The results suggest
      that the project developed in three stages: raising awareness, building
      partnerships, and lobbying for rights and services. Outcome measures indicate
      that the project was successful in lowering dropout rates and improving students'
      academic achievement. Analysis of interviews with students suggests that the
      project positively affected the students' perceptions by helping them reframe the
      social and emotional connotations of their learning disability. Students reported
      marked social and emotional change, including reduced stress and anxiety levels
      and increased self-esteem. CONCLUSIONS: Empowerment practices that are based on
      partnership, participation, advocacy and social change provide an alternative to
      rehabilitation via individual therapy.

PMID- 12519488
TI  - Body image and prosthesis satisfaction in the lower limb amputee.
AB  - PURPOSE: This study examines the relationship between prosthesis satisfaction and
      body image in lower limb prosthesis users, and the gendered variations within
      these relationships. METHOD: A total of 44 valid responses were obtained to an
      internet survey regarding prosthesis satisfaction, body image and phantom pain.
      Spearman Rho correlations were calculated for these three domains. RESULTS:
      Moderate to high negative correlations were observed between body image
      disturbance and prosthesis satisfaction. These were consistent across genders.
      Other relationships were also revealed, including positive correlations between
      prosthesis satisfaction with hours of use and negative correlations between
      prosthesis satisfaction and pain experience, although strong differences between
      genders were observed for these. The length of time for which respondents had had
      their prosthesis bore little relation to other variables. CONCLUSION: The present
      research is instructive of the close relationship between body image and
      prosthesis satisfaction, as well as gender variations in these relationships, in
      lower-limb prosthesis users. These findings have implications for targeted
      service provision in prosthetic rehabilitation.

PMID- 12519521
TI  - Introducing the objective structured clinical examination to a general practice
      residency programme: results of a French pilot study.
AB  - OSCE for evaluating clinical competence still remains limited in France. This
      study presents the results of the first experimental use of an OSCE as a
      formative assessment of French general practice trainees. Fifty trainees rotated
      through a circuit of 15 standardized patient-based OSCE cases. Differences in
      scores were determined by analysis of variance. Reliability was calculated with
      the coefficient alpha. Pearson correlations were used to determine the
      relationship between station scores and overall OSCE score. Written
      questionnaires based on Likert-type scales were used to measure OSCE feasibility.
      No difference was found between total session scores. Significant item-total
      score correlations were found for 12 of the 15 clinical problems. The reliability
      of the examination was 0.58. Most participants agreed that the clinical
      situations were realistic, simulated patients were believable and sampling of
      cases was representative of general practice. These data confirm the feasibility
      of OSCE in assessing performance of general practice trainees. Optimal training
      of observers should improve examination reliability. This study warrants further
      development to confirm its usefulness as a summative assessment tool.

PMID- 12519522
TI  - Further studies of shoulder and neck pain and exposures in customer service work
      with low biomechanical demands.
AB  - The aim of the study was to establish insight into work exposures that cause
      shoulder and neck pain among occupational groups that have low biomechanical
      exposure and experience work stress from client/customer contact, among other
      exposures. Four occupational groups were studied, in health care (n = 20), retail
      (n = 22), banking (n = 26), and university secretaries (n = 26), a total of 94
      volunteers. Thirty-nine were classified as pain-afflicted in the shoulder and
      neck, while 55 were pain-free. The subjects' perceptions of biomechanical and
      psychosocial exposures were established by use of quantitative questionnaires and
      by explorative interviews with open-ended questions, covering the same themes.
      Heart rate and trapezius EMG were recorded over a full workday and the following
      leisure period. Trapezius median and static activity during work were 3.3% and
      0.3% EMG(max), only marginally higher than trapezius activity in the leisure
      period (2.7% and 0.2% EMG(max)). The quantitative questionnaire did not identify
      any variable that correlated with shoulder and neck pain except perceived general
      tension. The interviews established that the interaction with clients or
      customers was an important source of work stress. Such stress appeared to be a
      complex entity not easily characterized by established psychosocial
      questionnaires. The physiological variables were at most weakly elevated in
      periods with high stress as compared to periods with low stress. The authors
      caution against relying on standardized quantitative questionnaires and/or
      physiological recordings to characterize work stress in occupations with
      emotional stress through client/customer service work.

PMID- 12519523
TI  - Significance of the dimensional view for visualizing relevant aspects of a
      production system in a co-operative planning process.
AB  - Pictorial visualization is expected to facilitate communication between
      industrial professionals when planning working environments and production
      systems. This hypothesis was investigated by studying how 24 participants
      including managers, supervisors, machine operators, and occupational health and
      safety officials, judged three types of computer animated visualization varying
      in dimensional view (scale and scope of a production line): shop floor
      view/survey of shop floor; production unit view/semi-survey of production unit;
      and workplace view/close-up of workplace, in relation to a set of planning
      issues. The participants participated in a controlled 2-day planning workshop,
      redesigning a fictitious manufacturing process by means of computer graphics, and
      then responded to a questionnaire. It can be concluded that shop floor view as
      well as production unit view are significant for survey planning issues, while
      all 3-dimensional views are significant for close-up planning issues.
      Analogously, all dimensional views are significant for technocentric planning
      issues, whereas only the workplace view is valuable for anthropocentric planning
      issues.

PMID- 12519524
TI  - The interaction between lid diameter, height and shape on wrist torque exertion
      in younger and older adults.
AB  - The following study investigated wrist torque strength measurements of a group of
      younger and older adults. The aim of the study was to examine the impact of
      shape, diameter and height of lid on wrist torque opening strength. Forty
      participants took part in the study in four groups, younger males and females and
      older males and females. Data were collected for 12 test pieces. Anthropometric
      data were also obtained for stature, weight, hand breadth, hand length, chuck
      grip force, grip force, lateral grip force and pinch grip force. The analysis of
      the wrist torque strength measurements found that participants could exert
      greater force with square test pieces compared to circular test pieces of the
      same diameter. Examination of the circular test pieces found that as diameter and
      height increased, so did torque exertion data for the test pieces between 20 mm
      and 50 mm diameter. The surface area of the test pieces was found to be highly
      correlated with the level of torque exertion, thus a linear model was developed
      to describe this relationship. The model could be used to predict maximal torque
      closure levels for use in the packaging industry. The anthropometric data
      revealed that as height, weight, hand length and hand breadth increased, there
      was a correlation with the levels of torque exerted. Future research needs to
      further examine the relationship between surface area and torque exerted and the
      design of spherical lids to increase the contact area between the hand and the
      lid.

PMID- 12519525
TI  - Visual performance on detection tasks with double-targets of the same and
      different difficulty.
AB  - This paper reports a study of measurement of horizontal visual sensitivity limits
      for 16 subjects in single-target and double-targets detection tasks. Two phases
      of tests were conducted in the double-targets task; targets of the same
      difficulty were tested in phase one while targets of different difficulty were
      tested in phase two. The range of sensitivity for the double-targets test was
      found to be smaller than that for single-target in both the same and different
      target difficulty cases. The presence of another target was found to affect
      performance to a marked degree. Interference effect of the difficult target on
      detection of the easy one was greater than that of the easy one on the detection
      of the difficult one. Performance decrement was noted when correct percentage
      detection was plotted against eccentricity of target in both the single-target
      and double-targets tests. Nevertheless, the non-significant correlation found
      between the performance for the two tasks demonstrated that it was impossible to
      predict quantitatively ability for detection of double targets from the data for
      single targets. This indicated probable problems in generalizing data for single
      target visual lobes to those for multiple targets. Also lobe area values obtained
      from measurements using a single-target task cannot be applied in a mathematical
      model for situations with multiple occurrences of targets.

PMID- 12519526
TI  - Age differences in perceived workload across a short vigil.
AB  - The main objective of this research was to investigate age differences in the
      perceived workload associated with the performance of a demanding, high event
      rate, vigilance task. Younger participants (n=26) aged 16 to 35 years (M=27.8)
      and older participants (n=24) aged 45 to 65 years (M=52.2) completed perceived
      workload scales (NASA-TLX) following a brief practice session (pretest) on the
      vigilance task, and then again following a test session (posttest) lasting nine
      minutes. In relation to the vigilance task, a statistically significant
      performance decrement was identified, but there was no evidence that performance
      differed according to age in respect to that decrement. However, a dissociation
      was found in relation to the perceived workload ratings: while no age differences
      were found in vigilance performance, the workload ratings revealed older
      participants to perceive a significantly greater increase in workload from
      pretest to posttest. These findings are considered theoretically in relation to
      the demands placed upon attentional resources, and their implications for both
      laboratory-based vigilance research, and workplace systems monitoring situations,
      are discussed.

PMID- 12519527
TI  - Judgments under uncertainty: representativeness or potential surprise?
AB  - Tversky and Kahneman's (1983) account of conjunctive probability judgment in
      terms of the representativeness heuristic is questioned. Instead, potential
      surprise (Shackle, 1969) is proposed as an important mechanism underlying
      subjective probability judgment. Study 1 reveals that, consistent with Shackle's
      theory, probabilities assigned to conjunctions are predominantly determined by
      the magnitude of the smaller component event probability. Also consistent with
      Shackle, Study 2 shows that for disjunctions, this role is performed by the
      larger component. Study 3 again contrasts the relative roles played by the
      component events in determining the value assigned to the conjunction. The
      results of the study are consistent with two reasoning processes: one
      analytically based, in which due account is taken of both component events, the
      other heuristic in nature and consistent with Shackle's theory of potential
      surprise. The implications of these results for a range of different types of
      judgment, e.g. with regard to person perception, stereotyping, categorization,
      and typicality, are evaluated.

PMID- 12519528
TI  - The role of masculinity and distinctiveness in judgments of human male facial
      attractiveness.
AB  - Masculinity and distinctiveness have been found to influence the attractiveness
      of human male faces. The relationship between masculinity and distinctiveness,
      however, has received little attention. In Expt 1, we examine how current
      averaging techniques and manipulated sexual dimorphism influence ratings of
      attractiveness, masculinity, and distinctiveness. In agreement with previous
      studies, composite faces were found to be more attractive than individual faces.
      Averaging resulted in increased ratings of attractiveness but decreased ratings
      of masculinity and distinctiveness. This supports both that attractiveness is
      related to averageness and findings showing a preference for feminine traits in
      male faces. When controlling for attractiveness, no significant relationship was
      found between masculinity and distinctiveness. Manipulating sexual dimorphism did
      not alter distinctiveness ratings, indicating that feminized and masculinized
      faces are equally distinctive. These results are suggestive that masculinity and
      distinctiveness are separable components in face perception. In Expt 2, we look
      to improve on previous studies utilizing composite faces by examining how
      averaging in texture-only or shape-only changes perceptions of attractiveness,
      masculinity, and distinctiveness. Averaging in both shape and texture were found
      to increase attractiveness independently, showing that the increased
      attractiveness of composites is due to the combined action of these two
      manipulations.

PMID- 12519529
TI  - Does performance on theory of mind tasks decline in old age?
AB  - In the first reported study of theory of mind (ToM; the ability to attribute
      mental states) in old age, Happe, Winner, and Brownell (1998) observed better
      performance on ToM tasks in older participants (mean age 73 years) than in young
      participants (mean age 21 years). We present two experiments exploring the
      generality of this finding. Experiment 1 compared young, young-old, and old-old
      age groups (mean ages 19, 67, and 81 years, respectively) on their understanding
      of ToM stories both with and without the need to remember the information, and
      control studies that did not require the ability to attribute mental states. For
      ToM stories with a memory load, the young group performed significantly better
      than both the young-old and old-old groups; without a memory load, the young and
      young-old groups performed significantly better than the old-old group. In
      Experiment 2, young and old-old age groups (mean ages 21 and 81 years,
      respectively) were compared on their understanding of ToM and control stories
      without the need to remember the information. Again, the young group performed
      significantly better than the old-old group on ToM stories. There were no
      significant age differences in performance on the control stories in either
      experiment. The age deficit on ToM stories remained significant after taking
      account of measures of vocabulary and processing speed (Experiments 1 and 2), and
      measures of executive functioning (Experiment 2).

PMID- 12519530
TI  - The mind machine: a mass participation experiment into the possible existence of
      extra-sensory perception.
AB  - This paper describes a mass participation experiment examining the possible
      existence of extra-sensory perception (ESP). The Mind Machine consisted of a
      specially designed steel cabinet containing a multi-media computer and large
      touch-screen monitor. The computer presented participants with a series of
      videoclips that led them through the experiment. During the experiment,
      participants were asked to complete an ESP task that involved them guessing the
      outcome of four random electronic coin tosses. All of their data were stored by
      the computer during an 11-month tour of some of Britain's largest shopping
      centres, museums, and science festivals. A total of 27,856 participants
      contributed 110,959 trials, and thus, the final database had the statistical
      power to detect the possible existence of a very small ESP effect. However, the
      cumulated outcome of the trials was consistent with chance. The experiment also
      examined the possible relationship between participants' ESP scores and their
      gender, belief in psychic ability, and degree of predicted success. The results
      from all of these analyses were non-significant. Also, scoring on 'clairvoyance'
      trials (where the target was selected prior to the participant's choice) was not
      significantly different from 'precognitive' trials (where the target was chosen
      after the participants had made their choice). Competing interpretations of these
      findings are discussed, along with suggestions for future research.

PMID- 12519531
TI  - Conditional reasoning and the Tower of Hanoi: the role of spatial and verbal
      working memory.
AB  - This paper reports a study that investigated the relationships between verbal and
      spatial measures of working memory capacity and performance on the Tower of Hanoi
      and a conditional reasoning task. Four working memory measures were included, a
      simple word span, a simple spatial span, a complex verbal span and a complex
      spatial span. The participants were 70 undergraduate students. Solution time on
      the Tower of Hanoi task correlated highly with both measures of spatial memory
      capacity, but not with the verbal working memory spans. In contrast, logical
      performance on the conditional reasoning task correlated highly with the complex
      verbal working memory span, but not with the spatial spans. A confirmatory factor
      analysis of the data elicited a best-fit model comprising a correlated spatial
      and verbal factor. The results are interpreted in the context of recent work that
      suggests a dissociation between spatial and verbal resources at the level of the
      central executive.

PMID- 12519532
TI  - Do cultural factors affect causal beliefs? Rational and magical thinking in
      Britain and Mexico.
AB  - In two experiments, unusual phenomena (spontaneous destruction of objects in an
      empty wooden box) were demonstrated to adult participants living in rural
      communities in Mexico. These were accompanied by actions which had no physical
      link to the destroyed object but could suggest either scientifically based (the
      effect of an unknown physical device) or non-scientifically based (the effect of
      a 'magic spell') causal explanations of the event. The results were compared to
      the results of the matching two experiments from the earlier study made in
      Britain. The expectation that scientifically based explanations would prevail in
      British participants' judgments and behaviours, whereas Mexican participants
      would be more tolerant toward magical explanations, received only partial
      support. The prevalence of scientific explanations over magical explanations was
      evident in British participants' verbal judgments but not in Mexican
      participants' judgments. In their behavioural responses under the low-risk
      condition, British participants rejected magical explanations more frequently
      than did Mexican participants. However, when the risk of disregarding the
      possible causal effect of magic was increased, participants in both samples
      showed an equal degree of credulity in the possible effect of magic. The data are
      interpreted in terms of the relationships between scientific and 'folk'
      representations of causality and object permanence.

PMID- 12519533
TI  - Sex differences in general knowledge, semantic memory and reasoning ability.
AB  - This paper has the three objectives of attempting to replicate a previous study
      in which it was found that males have substantially greater general knowledge in
      most fields or domains than females, and of determining how far sex differences
      in general knowledge are a function of differences in either Gf (fluid
      intelligence), or experience. The results confirmed the previous study to the
      effect that males have higher means in a general knowledge factor of
      approximately.50 d (half a standard deviation). It was found further that there
      was no significant sex difference in Gf measured by Baddeley's Grammatical
      Reasoning Test, and only a low correlation between general knowledge and Gf.
      Analysis of covariance showed that differential experience as indicated by 'A'
      level points and socio-economic status had only a marginal impact on the observed
      sex difference. The results are interpreted as showing that sex differences in
      general knowledge cannot be explained as a function of differences in either Gf
      or experience. It is proposed further that general knowledge should be regarded
      as a new second-order factor and designated as semantic memory.

PMID- 12519534
TI  - Visuospatial abilities of chess players.
AB  - The extent to which the acquisition of expertise in knowledge-rich domains, such
      as chess, can be influenced by general individual characteristics, such as
      intelligence, has remained unclear. Some previous studies with children have
      documented significant correlations between chess skill and performance on some
      psychometric tests, such as performance IQ. However, we found no evidence for a
      correlation between chess skill and visual memory ability in a group of adult
      chess players (N = 36, age = 28.4 years). This finding, together with other data
      in the literature, suggests that there is surprisingly little evidence that chess
      skill and visuospatial ability are associated in adults. Thus, visual memory
      ability, and perhaps visuospatial intelligence, may be relatively unimportant
      factors in the long-term acquisition of chess skill.

PMID- 12519535
TI  - Gamma and other cephalocondylic intramedullary nails versus extramedullary
      implants for extracapsular hip fractures.
AB  - BACKGROUND: Cephalocondylic intramedullary nails which are inserted proximally to
      distally (cephalocondylic) have been used for the surgical treatment of
      extracapsular hip fractures. OBJECTIVES: To compare all cephalocondylic
      intramedullary nails with extramedullary implants for the surgical treatment of
      extracapsular hip fractures in adults. This is the third substantive update of
      our original review which compared the Gamma nail with the sliding hip screw
      (SHS). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group
      trials register, MEDLINE, select orthopaedic journals and conference proceedings,
      and reference lists of relevant articles. We contacted trialists, colleagues and
      implant manufacturers. Date of the most recent search: August 2002. SELECTION
      CRITERIA: All randomised and quasi-randomised trials comparing cephalocondylic
      nails with extramedullary implants for extracapsular hip fractures. DATA
      COLLECTION AND ANALYSIS: Both reviewers independently assessed trial quality and
      extracted data. Additional information was sought from all trialists. Wherever
      appropriate and possible, results were pooled. MAIN RESULTS: Seventeen trials
      comparing the Gamma nail with the SHS were included, with data available for 2472
      patients. The Gamma nail was associated with an increased risk of operative and
      later fracture of the femur and an increased re-operation rate. There were no
      major differences in the incidence of wound infection, mortality or medical
      complications between implants. Data were inadequate for other outcomes. Five
      trials involving 623 patients compared the intramedullary hip screw (IMHS) with
      the SHS. Fracture fixation complications were more common in the IMHS group: all
      cases of operative and later fracture of the femur occurred in this group.
      Results for post-operative complications, mortality and functional outcomes were
      similar in the two groups. One study of 206 patients with a trochanteric fracture
      showed no advantages for proximal femoral nail (PFN) compared with the SHS. One
      trial of 60 patients reported favourable preliminary results for an experimental
      mini-invasive static intramedullary nail compared with the SHS. The one trial of
      230 patients comparing the Kuntscher-Y nail with the SHS, reported no major
      difference the outcome aside from a significantly increased number of patients
      with leg shortening, and a tendency for poorer recovery of mobility in the
      Kuntscher-Y nail group. Two trials, involving 65 patients with reverse and
      transverse fractures at the level of the lesser trochanter, compared an
      intramedullary nail (Gamma or PFN nail) with an extramedullary implant (a 90
      degree blade plate or dynamic condylar plate). The intramedullary nails were
      associated with better intra-operative results and fewer fracture fixation
      complications for these rare fractures. REVIEWER'S CONCLUSIONS: Given the lower
      complication rate of the SHS in comparison with intramedullary nails, it appears
      that for trochanteric fractures the SHS is superior. Further studies will be
      required to determine if different types of intramedullary nail produce the same
      results, or if intramedullary nails have advantages for selected fracture types,
      for example, reversed fracture lines and subtrochanteric fractures. From the
      evidence available, IMHS appears to have the same problems as the Gamma nail, but
      other theoretical advantages of the IHMS cannot be ruled out.

PMID- 12519536
TI  - Haemodilution for acute ischaemic stroke.
AB  - BACKGROUND: Ischaemic stroke interrupts the flow of blood to part of the brain.
      Haemodilution is thought to improve the flow of blood to the affected areas of
      the brain and thus reduce infarct size. OBJECTIVES: The objective of this review
      was to assess the effects of haemodilution in acute ischaemic stroke. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched
      January 2002), Medline (1966-June 2002) and conference abstracts. We contacted
      manufacturers and investigators in the field to identify any additional published
      and unpublished studies. SELECTION CRITERIA: Randomised trials of haemodilution
      treatment in people with acute ischaemic stroke. Only trials in which treatment
      was started within 72 hours of stroke onset were included. DATA COLLECTION AND
      ANALYSIS: Two reviewers assessed trial quality and independently extracted the
      data. MAIN RESULTS: Eighteen trials were included. A combination of venesection
      and plasma volume expander was used in eight trials. Ten trials used plasma
      volume expander alone. The plasma volume expander was dextran 40 in 12 trials,
      hydroxyethyl starch (HES) in five trials and albumin in one trial. Two trials
      tested haemodilution in combination with another therapy. Evaluation was blinded
      in 11 trials. Five trials probably included some patients with intracerebral
      haemorrhage. Haemodilution did not significantly reduce deaths within the first
      four weeks (odds ratio 1.09, 95% confidence interval 0.86 to 1.38). Similarly,
      haemodilution did not influence deaths within three to six months (odds ratio
      1.01, 95% confidence interval 0.84 to 1.22), or death and dependency or
      institutionalisation (odds ratio 0.98, 95% confidence interval 0.84 to 1.15). The
      results were similar in confounded and unconfounded trials, and in trials of
      isovolaemic and hypervolaemic haemodilution. No statistically significant
      benefits were documented for any particular type of haemodiluting agents, but the
      statistical power to detect effects of HES and albumin was weak. Six trials
      reported venous thromboembolic events. There was a tendency towards reduction in
      deep venous thrombosis and/or pulmonary embolism at three to six months follow-up
      (odds ratio 0.59, 95% confidence interval 0.33 to 1.06). There was no increased
      risk of serious cardiac events among haemodiluted patients. REVIEWER'S
      CONCLUSIONS: The overall results of this review are compatible both with modest
      benefit and moderate harm of haemodilution therapy for acute ischaemic stroke.
      This therapy has not been proven to improve survival or functional outcome.

PMID- 12519537
TI  - Nicotine replacement therapy for smoking cessation.
AB  - BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine
      from cigarettes. This reduces withdrawal symptoms associated with smoking
      cessation thus helping resist the urge to smoke cigarettes. OBJECTIVES: The aims
      of this review were to determine the effectiveness of the different forms of
      nicotine replacement therapy (chewing gum, transdermal patches, nasal spray,
      inhalers and tablets) in achieving abstinence from cigarettes, or a sustained
      reduction in amount smoked; to determine whether the effect is influenced by the
      clinical setting in which the smoker is recruited and treated, the dosage and
      form of the NRT used, or the intensity of additional advice and support offered
      to the smoker; to determine whether combinations of NRT are more effective than
      one type alone; and to determine its effectiveness compared to other
      pharmacotherapies. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction
      Group trials register in July 2002. SELECTION CRITERIA: Randomized trials in
      which NRT was compared to placebo or no treatment, or where different doses of
      NRT were compared. We excluded trials which did not report cessation rates, and
      those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We
      extracted data in duplicate on the type of subjects, the dose and duration and
      form of nicotine therapy, the outcome measures, method of randomization, and
      completeness of follow-up. The main outcome measure was abstinence from smoking
      after at least six months of follow-up. We used the most rigorous definition of
      abstinence for each trial, and biochemically validated rates if available. Where
      appropriate, we performed meta-analysis using a fixed effects model (Peto). MAIN
      RESULTS: We identified 110 trials; 96 with a non NRT control group. The odds
      ratio for abstinence with NRT compared to control was 1.74 (95% confidence
      interval 1.64 - 1.86), The odds ratios for the different forms of NRT were 1.66
      for gum, 1.74 for patches, 2.27 for nasal spray, 2.08 for inhaled nicotine and
      2.08 for nicotine sublingual tablet/lozenge. These odds were largely independent
      of the duration of therapy, the intensity of additional support provided or the
      setting in which the NRT was offered. In highly dependent smokers there was a
      significant benefit of 4 mg gum compared with 2mg gum (odds ratio 2.67, 95%
      confidence interval 1.69 - 4.22). There was weak evidence that combinations of
      forms of NRT are more effective. Higher doses of nicotine patch may produce small
      increases in quit rates. Only one study directly compared NRT to another
      pharmacotherapy, in which bupropion was significantly more effective than
      nicotine patch or placebo. REVIEWER'S CONCLUSIONS: All of the commercially
      available forms of NRT (nicotine gum, transdermal patch, the nicotine nasal
      spray, nicotine inhaler and nicotine sublingual tablets/lozenges) are effective
      as part of a strategy to promote smoking cessation. They increase quit rates
      approximately 1.5 to 2 fold regardless of setting. The effectiveness of NRT
      appears to be largely independent of the intensity of additional support provided
      to the smoker. Provision of more intense levels of support, although beneficial
      in facilitating the likelihood of quitting, is not essential to the success of
      NRT. There is promising evidence that bupropion may be more effective than NRT
      (either alone or in combination). However, its most appropriate place in the
      therapeutic armamentarium requires further study and consideration.

PMID- 12519538
TI  - Prophylactic antibiotics for inhibiting preterm labour with intact membranes.
AB  - BACKGROUND: The contribution of subclinical genital tract infection to the
      aetiology of preterm birth is gaining increasing recognition, but the role of
      prophylactic antibiotic treatment in the management of preterm labour is
      uncertain. Since rupture of the membranes is an important factor in the
      progression of preterm labour, it is important to see if the routine
      administration of antibiotics confers any benefit, prior to membrane rupture.
      OBJECTIVES: To assess the effects of prophylactic antibiotics administered to
      women in preterm labour with intact membranes, on maternal and neonatal outcomes.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's
      specialised register of controlled trials (May 2002), the Cochrane Controlled
      Trials Register (The Cochrane Library, Issue 1, 2002), MEDLINE (1965 to May
      2002). Other sources included contacting recognised experts and cross referencing
      relevant material. SELECTION CRITERIA: Randomised trials which compared
      antibiotic treatment with placebo or no treatment for women in preterm labour
      (between 20 and 36 weeks' gestation) with intact membranes. DATA COLLECTION AND
      ANALYSIS: Standard methods of the Cochrane Collaboration and the Cochrane
      Pregnancy and Childbirth Group were used. Evaluation of methodological quality
      and trial data extraction were undertaken independently by the authors. Results
      are presented using relative risk for categorical data and weighted mean
      difference for continuous data. MAIN RESULTS: This review has been updated (2002)
      to include data from the 'ORACLE II 2001' trial (six times larger than the
      previous 10 trials combined), which now dominates the results of this review.
      Meta-analysis of the 11 included trials (7428 women enrolled) shows a reduction
      in maternal infection with the use of prophylactic antibiotics (relative risk
      0.74, 95% confidence interval 0.64 to 0.87) but fails to demonstrate a benefit or
      harm for any of the prespecified neonatal outcomes. REVIEWER'S CONCLUSIONS: This
      review fails to demonstrate a clear overall benefit from prophylactic antibiotic
      treatment for preterm labour with intact membranes on neonatal outcomes and
      raises concerns about increased neonatal mortality for those who received
      antibiotics. This treatment cannot therefore be currently recommended for routine
      practice. Further research may be justified (when sensitive markers for
      subclinical infection become available) in order to determine if there is a
      subgroup of women who could experience benefit from antibiotic treatment for
      preterm labour prior to membrane rupture, and to identify which antibiotic or
      combination of antibiotics is most effective.

PMID- 12519539
TI  - Calcium antagonists for aneurysmal subarachnoid haemorrhage.
AB  - BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients
      with subarachnoid haemorrhage. Its pathogenesis has not been elucidated yet, but
      may be related to vasospasm. Experimental studies have indicated that calcium
      antagonists can prevent or reverse vasospasm. Calcium antagonists have been
      studied in several trials, but data are conflicting. There is no overview
      concerning all available calcium antagonists. OBJECTIVES: To determine whether
      calcium antagonists improve outcome in patients with aneurysmal subarachnoid
      haemorrhage (SAH). SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials
      Register (last searched November 2001). In addition, we handsearched two Russian
      journals (1990-1995) and contacted trialists and pharmaceutical companies to
      identify further studies SELECTION CRITERIA: All completed, unconfounded, truly
      randomised controlled trials comparing any calcium antagonist with control,
      within ten days of SAH onset. Eleven trials that met the inclusion criteria were
      included in the overview. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted the data and assessed trial quality. Trialists were
      contacted to obtain missing information MAIN RESULTS: We analysed 11 trials
      totaling 2804 randomised patients with subarachnoid haemorrhage (1376 in the
      treatment and 1428 in the control group). The drugs analysed were: nimodipine
      (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877
      (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by
      angiography or autopsy. Overall, calcium antagonists significantly reduced the
      risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95%
      CI 0.72 to 0.93); the absolute risk reduction was 5.1%, the corresponding number
      of patients needed to treat to prevent a single poor outcome event is 20. For
      oral nimodipine alone the RR was 0.69 (0.58 to 0.84). The RR of death on
      treatment with calcium antagonists was 0.94 (95% CI 0.80 to 1.10), that of
      ischaemic neurological deficits 0.67 (95% CI 0.59 to 0.76), and that of CT-scan
      documented cerebral infarction 0.80 (95% CI 0.71 to 0.89). REVIEWER'S
      CONCLUSIONS: Calcium antagonists reduce the proportion of patients with poor
      outcome and ischaemic neurological deficits after aneurysmal SAH. The results for
      'poor outcome' are statistically robust, but depend largely on one large trial
      with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The
      evidence for nimodipine is not beyond every doubt, but given the potential
      benefits and modest risks associated with this treatment, against the background
      of a devastating natural history, oral nimodipine (60 mg every 4 hours) is
      indicated in patients with aneurysmal SAH. Intravenous administration of calcium
      antagonists cannot be recommended on the basis of the present evidence. For oral
      nimodipine uncertainty remains regarding the (dis)advantages in patients in poor
      clinical condition on admission or in patients with established cerebral
      ischaemia, the optimal dose and time window, the question whether other types of
      calcium antagonists offer better protection and the intermediate factors through
      which nimodipine exerts its beneficial effect after aneurysmal SAH.

PMID- 12519540
TI  - Heparin, low molecular weight heparin and physical methods for preventing deep
      vein thrombosis and pulmonary embolism following surgery for hip fractures.
AB  - BACKGROUND: Hip fracture patients have a high risk of thrombo-embolic
      complications following surgical management. OBJECTIVES: To examine the effects
      of heparin (unfractionated (U), and low molecular weight (LMW) heparins), and
      physical methods (compression stockings, calf or foot pumps) for prevention of
      deep venous thrombosis (DVT) and pulmonary embolism after surgery for hip
      fracture in the elderly. SEARCH STRATEGY: We searched the Cochrane
      Musculoskeletal Injuries Group specialised register (up to March 2002), MEDLINE
      (1966 to March 2002), EMBASE (1980 to March 2002), CINAHL (1982 to February week
      4 2002), Current Contents (1993 week 26 to 2002 week 12), reference lists of
      published articles and contacted trialists and other workers in the field. Date
      of most recent search: March 2002. SELECTION CRITERIA: Randomised and quasi
      randomised trials evaluating the use of heparins and physical agents for
      prevention of DVT and pulmonary embolism in patients undergoing surgery for hip
      fracture. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      methodological quality and extracted data. Trials were grouped into five
      categories (heparin versus control, mechanical versus control, LMW heparin versus
      U heparin, heparin versus mechanical, and miscellaneous) and results pooled where
      possible. MAIN RESULTS: The 31 included trials involved at least 2958
      predominantly female and elderly patients. Overall, trial quality was
      disappointing. Ten trials involving 826 patients which compared U heparin with
      control, and five trials of 373 patients which compared LMW heparin with control,
      showed a reduction in the incidence of lower limb DVT (124/474 (26%) versus
      219/519 (42%); relative risk (RR) 0.60; 95% confidence interval (CI) 0.50 to
      0.71). There were insufficient data to confirm the efficacy of either agent in
      the prevention of pulmonary embolism. There was no statistically significant
      difference in overall mortality (42/356 (12%) versus 38/374 (10%); RR 1.16; 95%CI
      0.77 to 1.74). Data were inadequate for all other outcomes including wound
      complications. There is insufficient evidence from five trials, involving 644
      patients, to establish if LMW heparin was superior to U heparin. Most trials
      evaluating heparins had methodological defects. Five trials, involving 487
      patients, testing mechanical pumping devices were also methodologically flawed,
      and so pooled results need to be viewed cautiously. Mechanical pumping devices
      may protect against DVT (16/221 (7%) versus 52/229 (22%); RR 0.31; 95%CI 0.19 to
      0.51) and pulmonary embolism. Data were insufficient to establish any effect on
      the incidence of fatal pulmonary embolism and overall mortality. Problems with
      skin abrasion and compliance were reported. REVIEWER'S CONCLUSIONS: U and LMW
      heparins protect against lower limb DVT. There is insufficient evidence to
      confirm either protection against pulmonary embolism or an overall benefit, or to
      distinguish between various applications of heparin. Foot and calf pumping
      devices appear to prevent DVT, may protect against pulmonary embolism, and reduce
      mortality, but compliance remains a problem. Good quality trials of mechanical
      methods as well as direct comparisons with heparin and low dose aspirin should be
      considered.

PMID- 12519541
TI  - Extramedullary fixation implants and external fixators for extracapsular hip
      fractures.
AB  - BACKGROUND: Extramedullary fixation of hip fractures involves the application of
      a plate and screws to the lateral side of the proximal femur. In external
      fixators, the stabilising component is held outside the thigh by pins or screws
      driven into the bone on either side of the fracture. OBJECTIVES: To compare
      different types of extramedullary fixation implants and external fixators for
      treating extracapsular hip fracture in adults. SEARCH STRATEGY: We searched the
      Cochrane Musculoskeletal Injuries Group specialised register and reference lists
      of relevant articles up to July 2002. SELECTION CRITERIA: All randomised or quasi
      randomised trials comparing these devices for the fixation of extracapsular hip
      fracture in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed trial quality, using a ten item scale, and extracted data. Additional
      information was sought from trialists when required. Wherever appropriate, data
      from comparable trials were pooled. MAIN RESULTS: Two trials examining the
      Gotfried plate and one, an external fixator, are newly included in this update.
      All 13 included trials had methodological flaws, which may affect the validity of
      their results. The limited data available for three trials (355 patients)
      comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw
      (SHS) indicated an increased risk of fixation failure for fixed nail plates. The
      two trials (433 patients) comparing the RAB plate with the SHS had contrasting
      results, notably in terms of operative complications, fixation failure and
      anatomical restoration. One trial (100 patients) found no significant difference
      between the Pugh nail and the SHS. Two trials (292 patients) compared the Medoff
      plate with the SHS. One trial reported higher operative blood loss and longer
      operative times for the Medoff plate. There was a lower risk of fixation failure
      for unstable trochanteric fractures fixed with the Medoff plate. Two trials
      involving, respectively, unstable trochanteric fractures (569 patients) and
      subtrochanteric fractures (107 patients) compared the Medoff plate with three
      different screw-plate systems. There were no statistically significant
      differences in outcome for trochanteric fractures. For subtrochanteric fractures,
      there was a tendency to less fixation failure for the Medoff plate, but no
      evidence for differences in longer-term outcomes. Two trials (226 patients)
      compared the Gotfried percutaneous plate with a SHS. A higher intra-operative
      fixation failure rate of the Gotfried plate indicated some specific restriction
      to its use. The Gotfried plate appeared to involve lower operative blood losses.
      There were insufficient data on long term outcomes. One trial (100 patients)
      provided some evidence of less operative trauma and speedier recovery for
      external fixation when compared with the SHS. Final outcomes appeared similar.
      REVIEWER'S CONCLUSIONS: The fixed nail plate has higher risks of implant breakage
      and fixation failure than the SHS. Though insufficient evidence on other outcomes
      is available from randomised trials, the increased fixation failure rate is a
      major consideration and thus the SHS appears preferable. Insufficient information
      is available to draw firm conclusions of significant differences between the SHS
      and either the RAB, the Pugh, the Medoff or the Gotfried plates, or an external
      fixator.

PMID- 12519542
TI  - Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors
      for acute stroke.
AB  - BACKGROUND: Nitric oxide has several effects that may be beneficial in ischaemic
      stroke and useful in the management of high blood pressure in acute stroke. Some
      forms of nitric oxide synthase inhibition may also be beneficial. However, high
      concentrations of nitric oxide are likely to be toxic to brain tissue.
      OBJECTIVES: The objective of this review was to assess the effects of nitric
      oxide donors, L-arginine, or nitric oxide synthase-inhibitors in people with
      acute stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials
      Register (last searched in March 2002), EMBASE (1980-March 2002), MEDLINE (1966
      March 2002), and ISI Science Citation Indexes (1981-March 2002). We contacted
      drug companies and researchers in the field. SELECTION CRITERIA: Randomised and
      quasi-randomised trials comparing nitric oxide donors, L-arginine, or nitric
      oxide synthase-inhibitors in patients within one week of onset of confirmed
      stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the
      inclusion criteria. The data are given as weighted mean difference (WMD) or odds
      ratio (OR) with 95% confidence intervals (CI). MAIN RESULTS: Two small completed
      trials (127 patients) of transdermal glyceryl trinitrate (GTN), a nitric oxide
      donor, were found. GTN lowered 24 hour ambulatory systolic blood pressure by 7.9
      mmHg (95% CI 0.1, 15.8) and increased heart rate (WMD 6.2 beats per minute, 95%
      CI 2.7, 9.8). Treatment with GTN was not associated with statistically
      significant effects on end-of-treatment death, or combined death or
      deterioration, or end-of-trial death, combined death or dependency, or combined
      death or institutionalisation. REVIEWER'S CONCLUSIONS: There is currently
      insufficient evidence from randomised trials on the effects of nitric oxide
      donors, L-arginine, or nitric oxide synthase-inhibitors in patients with acute
      stroke to recommend their use. A large controlled trial of glyceryl trinitrate
      patches is underway.

PMID- 12519543
TI  - Piracetam for acute ischaemic stroke.
AB  - BACKGROUND: Piracetam has neuroprotective and antithrombotic effects which may
      help to reduce death and disability in people with acute stroke. OBJECTIVES: The
      objective of this review was to assess the effects of piracetam in acute presumed
      ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Review Group
      Trials Register (last searched April 2001). In addition we searched the Cochrane
      Controlled Trials Register (Cochrane Library 2001, issue 2), MEDLINE (1966-April
      2001), EMBASE (1980-April 2001), and ISI Science Citation Index (1981- April
      2001). We also handsearched 15 journals and contacted the manufacturer to
      identify further published and unpublished studies. SELECTION CRITERIA:
      Randomised trials comparing piracetam with control, with at least mortality
      reported and entry to the trial within approximately 48 hours of stroke onset.
      DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial
      quality and this was checked by the other two reviewers. Study authors were
      contacted for missing information. MAIN RESULTS: Three trials involving 1002
      people were included, with one trial contributing 93% of the data. Participants'
      ages ranged from 40 to 85, and both sexes were equally represented. Piracetam was
      associated with a statistically non significant increase in death at one month
      (approximately 31% increase, 95% confidence interval 81% increase to 5%
      reduction). This trend was no longer apparent in the large trial after correction
      for imbalance in stroke severity. Limited data showed no difference between the
      treatment and control groups for functional outcome, dependency or proportion of
      patients dead or dependent. Adverse effects were not reported. REVIEWER'S
      CONCLUSIONS: There is some suggestion (but no statistically significant result)
      of an unfavourable effect of piracetam on early death, but this may have been
      caused by baseline differences in stroke severity in the trials. There is not
      enough evidence to assess the effect of piracetam on dependency.

PMID- 12519544
TI  - Supported housing for people with severe mental disorders.
AB  - BACKGROUND: There has been a significant reduction in the number of people with
      severe mental illness who spend extended periods in long-stay hospitals.
      Psychiatric and social services, both statutory and voluntary, aim to assist
      these people to stay in their local community. District health authorities, local
      authorities, housing associations and voluntary organisations are jointly
      expected to provide support for people with severe mental disorder/s. This
      'support' may well involve some sort of special housing. OBJECTIVES: To determine
      the effects of supported housing schemes compared with outreach support schemes
      or 'standard care' for people with severe mental disorder/s living in the
      community. SEARCH STRATEGY: Cochrane Schizophrenia Group's Register of trials
      (February 2001) and the Cochrane Library (Issue 1, 2001) were searched using
      relevant phrases. These databases are compiled by methodical searches of BIOSIS,
      CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO,
      RUSSMED, Sociofile, supplemented with hand searching of relevant journals and
      numerous conference proceedings. Reference list screening of relevant papers was
      performed. SELECTION CRITERIA: Relevant randomised, or quasi-randomised, trials
      dealing with people with 'severe mental disorder/s' allocated to supported
      housing, outreach support schemes or standard care focusing on outcomes of
      service utilisation, mental state, satisfaction with care, social functioning,
      quality of life, and economic data, were sought. DATA COLLECTION AND ANALYSIS:
      Studies were reliably selected, quality rated and data extracted. For dichotomous
      data, relative risks (RR) would have been estimated, with the 95% confidence
      intervals (CI). Where possible, the number needed to treat statistic (NNT) was to
      have been calculated. Analysis would have been by intention-to-treat. Normal
      continuous data were to have been summated using the weighted mean difference
      (WMD). Scale data were to have been presented for only those tools that had
      attained pre-specified levels of quality. Tests of heterogeneity and for
      publication bias were to have been undertaken. MAIN RESULTS: No studies met the
      inclusion criteria although 139 citations were acquired from the searches.
      REVIEWER'S CONCLUSIONS: Dedicated schemes whereby people with severe mental
      illness are located within one site or building with assistance from professional
      workers have potential for great benefit as they provide a 'safe haven' for
      people in need of stability and support. This, however, may be at the risk of
      increasing dependence on professionals and prolonging exclusion from the
      community. Whether or not the benefits outweigh the risks can only be a matter of
      opinion in the absence of reliable evidence. There is an urgent need to
      investigate the effects of supported housing on people with severe mental illness
      within a randomised trial.

PMID- 12519545
TI  - Vitamin A supplementation for preventing morbidity and mortality in very low
      birthweight infants.
AB  - BACKGROUND: Vitamin A is necessary for normal lung growth and the ongoing
      integrity of respiratory tract epithelial cells. Preterm infants have low vitamin
      A status at birth and this has been associated with increased risk of developing
      chronic lung disease. Several studies have been undertaken to assess whether
      vitamin A supplementation beyond that routinely given in multivitamin
      preparations can reduce the incidence of this outcome. OBJECTIVES: To assess the
      benefit of supplementation with vitamin A in very low birthweight infants. SEARCH
      STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE
      up to June 2002, Cochrane Controlled Trials Register (The Cochrane Library, Issue
      2, 2002), and Science Citation Index. The reference lists of relevant trials,
      recent issues of paediatric and nutrition journals, abstracts and proceedings
      from relevant conferences in the English language were hand searched. SELECTION
      CRITERIA: Randomised controlled trials which compared the effects of supplemental
      vitamin A with standard vitamin A regimes in infants with birthweight </=1500g,
      and which reported clinical outcomes (death, chronic lung disease or
      bronchopulmonary dysplasia) and/or vitamin A concentrations were considered for
      the review. DATA COLLECTION AND ANALYSIS: Data on mortality, requirement for
      supplemental oxygen at one month of age and at 36 weeks post-menstrual age,
      retinopathy of prematurity and nosocomial sepsis were excerpted by both reviewers
      independently. Data analysis was conducted according to the standards of the
      Cochrane Neonatal Review Group. MAIN RESULTS: Seven eligible trials were
      identified, one having a much larger sample size than the others combined. The
      meta-analysis suggests supplementation with vitamin A results in benefit in terms
      of reducing death or oxygen requirement at one month of age [summary RR 0.93
      (0.88, 0.99), RD -0.05 (-0.10, -0.01), NNT 20 (10, 100) and oxygen requirement at
      36 weeks post-menstrual age [summary RR 0.87 (0.77, 0.99), RD -0.07 (-0.14, 
      0.01), NNT 14 (7, 100)], and trends towards reduction in oxygen requirement in
      survivors at one month of age [summary RR 0.93 (0.86, 1.01) and death or oxygen
      requirement at 36 weeks post-menstrual age [summary RR 0.91 (0.83, 1.00)]. Meta
      analysis of the three studies from which data on retinopathy of prematurity are
      available suggests a trend towards reduced incidence in vitamin A supplemented
      infants. REVIEWER'S CONCLUSIONS: Supplementing very low birthweight infants with
      vitamin A is associated with a reduction in death or oxygen requirement at one
      month of age, and oxygen requirement amongst survivors at 36 weeks post-menstrual
      age, with this latter outcome being confined to infants with birthweight less
      than 1000g. Whether clinicians decide to utilise repeat intramuscular doses of
      vitamin A to prevent chronic lung disease may depend upon the local incidence of
      this outcome and the value attached to achieving a modest reduction in this
      outcome, balanced against the lack of other proven benefits and the acceptability
      of treatment. The benefits, in terms of vitamin A status, safety and
      acceptability of delivering vitamin A in an intravenous emulsion compared with
      repeat intramuscular injections, should be assessed in a further trial.

PMID- 12519546
TI  - Interventions for treating tuberculous pericarditis.
AB  - BACKGROUND: Tuberculous pericarditis - tuberculosis infection of the pericardial
      membrane (pericardium) covering the heart - is becoming more common. The
      infection can result in fluid around the heart or fibrosis of the pericardium,
      which can be fatal. OBJECTIVES: In people with tuberculous pericarditis, to
      evaluate the effects on death, life-threatening conditions, and persistent
      disability of: (1) 6-month antituberculous drug regimens compared with regimens
      of 9 months or more; (2) corticosteroids; (3) pericardial drainage; and (4)
      pericardiectomy. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases
      Group trials register (June 2002), the Cochrane Controlled Trials Register (Issue
      2, 2002), MEDLINE (1966 to June 2002), EMBASE (1980 to May 2002), and checked the
      reference lists of existing reviews. We also contacted organizations and
      individuals working in the field. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials of treatments for tuberculous pericarditis. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. Meta-analysis using fixed effects models calculated summary
      statistics, provided there was no statistically significant heterogeneity, and
      expressed results as relative risk. Study authors were contacted for additional
      information. MAIN RESULTS: Four trials met the inclusion criteria, with a total
      of 469 participants. Treatments tested were adjuvant steroids and surgical
      drainage. Two trials with a total of 383 participants tested adjuvant steroids in
      participants with suspected tuberculous pericarditis in the pre-HIV era. Fewer
      participants died in the intervention group, but numbers were small (relative
      risk [RR] 0.65; 95% confidence interval [CI] 0.36 to 1.16, n = 350). One small
      trial tested steroids in HIV positive participants with effusion showed a similar
      pattern (RR 0.50; 95% CI 0.19 to 1.28, n = 58). One trial examined open surgical
      drainage compared with conservative management, and showed surgery relieved
      cardiac tamponade. REVIEWER'S CONCLUSIONS: Steroids could have important clinical
      benefits, but the trials published to date are too small to demonstrate an
      effect. This requires large placebo controlled trials. Subgroup analysis could
      explore whether effusion or fibrosis modify the effects. Therapeutic
      pericardiocentesis under local anaesthesia and pericardiectomy also require
      further evaluation.

PMID- 12519547
TI  - Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.
AB  - BACKGROUND: The newer 5-ASA preparations were intended to avoid the adverse
      effects of SASP while maintaining its therapeutic benefits. The efficacy and
      safety of 5-ASA preparations have been evaluated in numerous clinical trials that
      have often lacked sufficient statistical power to arrive at definitive
      conclusions. Previously, it was found that newer 5-ASA drugs were more effective
      than placebo but no more effective than SASP in inducing remission in ulcerative
      colitis. This updated review includes more recent studies and evaluates the
      effectiveness, dose-responsiveness, and safety of 5-ASA preparations in terms of
      more precise outcome measures. OBJECTIVES: To assess the efficacy, dose
      responsiveness and safety of the newer release formulations of 5-aminosalicylic
      acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of
      remission in ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature
      search for relevant studies (1981-2002) was performed using MEDLINE, BIOS, the
      Cochrane Controlled Trials Register, the Cochrane IBD Group Specialized Trials
      Register, and the Science Citation Index, followed by a manual search of
      reference lists from previously retrieved articles, review articles, symposia
      proceedings, and abstracts from major gastrointestinal conferences. SELECTION
      CRITERIA: Studies were accepted for analysis if they were prospective,
      randomized, double-blinded, and placebo- or SASP-controlled clinical trials of
      parallel design with treatment duration of at least six months. DATA COLLECTION
      AND ANALYSIS: Based on an intention to treat principle, the primary outcome was
      the failure to maintain clinical or endoscopic remission. Secondary outcomes were
      the number of patients experiencing adverse events, the number of patients
      withdrawn due to adverse events, and exclusions or withdrawals after entry into
      the study (not due to relapse). All data were analyzed using the Peto odds ratio
      and corresponding 95% confidence intervals (CI). MAIN RESULTS: The Peto odds
      ratio for the failure to maintain clinical or endoscopic remission (withdrawals
      and relapses) for 5-ASA versus placebo was 0.47 (95% CI, 0.36 to 0.62) with an
      NNT of 6. These values were also calculated for the trials in which SASP and 5
      ASA were compared, revealing an odds ratio of 1.29 (95% CI, 1.05 to 1.57), with a
      negative NNT value (-19), suggesting a higher degree of therapeutic effectiveness
      for SASP. SASP and 5-ASA had similar adverse event profiles, with odds ratios of
      1.16(0.62 to 2.16), and 1.31(0.86 to 1.99), respectively. The NNH values were
      determined to be 171 and 78 respectively. REVIEWER'S CONCLUSIONS: The newer 5-ASA
      preparations were superior to placebo in maintenance therapy. However, the newer
      preparations had a statistically significant therapeutic inferiority relative to
      SASP. This review updates the existing review of oral 5-aminosalicylic acid for
      maintenance of remission in ulcerative colitis which was published in the
      Cochrane Library (Issue 3, 2002).

PMID- 12519548
TI  - Manual therapy for asthma.
AB  - BACKGROUND: A variety of manual therapies with similar postulated biologic
      mechanisms of action are commonly used to treat patients with asthma. Manual
      therapy practitioners are also varied, including physiotherapists, respiratory
      therapists, chiropractic and osteopathic physicians. A systematic review across
      disciplines is warranted. OBJECTIVES: To evaluate the evidence for the effects of
      manual therapies for treatment of patients with bronchial asthma. SEARCH
      STRATEGY: Trials were searched in computerized general (EMBASE, CINAHL and
      MEDLINE) and specialized databases (Cochrane Complementary Medicine Field,
      Cochrane Rehabilitation Field, ICL, and MANTIS). In addition, bibliographies from
      included studies were assessed, and authors of known studies were contacted for
      additional information about published and unpublished trials. Date of most
      recent search: February 2002. SELECTION CRITERIA: Trials were included if they:
      (1) were randomised; (2) included asthmatic children or adults; (3) examined one
      or more types of manual therapy; and (4) included clinical outcomes. DATA
      COLLECTION AND ANALYSIS: All three reviewers independently extracted data and
      assessed trial quality using a standard form. MAIN RESULTS: From 393 unique
      citations, 59 full text articles were retrieved and evaluated, which resulted in
      nine citations to five RCTs (290 patients) suitable for inclusion. Trials could
      not be pooled statistically because studies that addressed similar interventions
      used disparate patient groups or outcomes. The methodological quality of one of
      two trials examining chiropractic manipulation was good and neither trial found
      significant differences between chiropractic spinal manipulation and a sham
      manoeuvre on any of the outcomes measured. Quality of the remaining three trials
      was poor. One small trial compared massage therapy with a relaxation control
      group and found significant differences in many of the lung function measures
      obtained. However, this trial had poor reporting characteristics and the data
      have yet to be confirmed. One small trial compared chest physiotherapy to placebo
      and one small trial compared footzone therapy to a no treatment control. Neither
      trial found differences in lung function between groups. REVIEWER'S CONCLUSIONS:
      There is insufficient evidence to support the use of manual therapies for
      patients with asthma. There is a need to conduct adequately-sized RCTs that
      examine the effects of manual therapies on clinically relevant outcomes. Future
      trials should maintain observer blinding for outcome assessments, and report on
      the costs of care and adverse events. Currently, there is insufficient evidence
      to support or refute the use of manual therapy for patients with asthma.

PMID- 12519549
TI  - Allopurinol for chronic prostatitis.
AB  - BACKGROUND: Chronic prostatitis is a condition that causes men substantial
      morbidity through the associated constellation of urinary symptoms, sexual
      dysfunction, and pelvic pain. The etiology of chronic prostatitis is unknown, and
      the many and varied treatments for chronic prostatitis reflect in part this
      knowledge gap. One novel etiologic theory is that the reflux of urine into
      prostatic ducts causes prostatic inflammation via high concentrations of purine
      and pyrimidine base-containing metabolites in prostatic secretions. This theory
      has led to the use of allopurinol for treatment of chronic prostatitis in hopes
      of lowering prostatic levels of uric acid and improving symptoms. OBJECTIVES: To
      determine the effects of allopurinol in the treatment of chronic prostatitis
      SEARCH STRATEGY: Trials were searched in computerized general and specialized
      databases (MEDLINE, Cochrane Library, Cochrane Prostate Group database),
      bibliographies of obtained articles, and direct contact with authors. SELECTION
      CRITERIA: All randomized trials of allopurinol versus placebo used to treat
      patients with chronic prostatitis. Acute prostatitis, bacterial prostatitis, and
      asymptomatic prostatitis were excluded. The main outcome measure was the change
      in patient-reported discomfort. DATA COLLECTION AND ANALYSIS: The reviewers
      extracted the data independently for the outcomes of change in patient-reported
      discomfort, investigator graded prostate pain, leukocyte counts, and biochemical
      indices. MAIN RESULTS: In this update, no new trials were identified (08/2002).
      Only one trial with 54 men lasting 240 days (with 330 days of follow-up) met
      study inclusion criteria. There was a statistically significant change favoring
      allopurinol in patient-reported discomfort between the study and control groups
      at follow-up. Between days 45-225, the mean score was -0.95 (s.d. 0.19) for the
      allopurinol group (7 men), compared with -0.47 (s.d. 0.21) for the placebo group
      (7 men). The weighted mean difference (WMD) was -0.48 (95%CI -0.690, -0.270). The
      mean score between days 45-135 was -1.08 (s.d. 1.29) for the 25 men in the
      allopurinol group, compared with -0.21 (sd 0.97) for the 14 men in the control
      group. The WMD was -0.87 (95%CI -1.587, -0.153). The allopurinol group had
      significantly less investigator graded prostate pain and had lower levels of
      serum urate, urine urate, and expressed prostatic secretion urate and xanthine.
      No significant differences between the two groups regarding leukocyte counts were
      found. No patient receiving allopurinol had any significant side effects. Three
      patients in the placebo group dropped out because of side effects. REVIEWER'S
      CONCLUSIONS: One small trial of allopurinol for treating chronic prostatitis
      showed improvements in patient-reported symptom improvement, investigator-graded
      prostate pain, and biochemical parameters. However, the data provided, the
      measures used, and the statistics presented do not make these findings convincing
      that changes in urine and prostatic secretion composition regarding purine and
      pyrimidine bases resulted in the relief of symptoms. Further studies of
      allopurinol treatment using standardized and validated outcomes measures and
      analyses are necessary to determine whether allopurinol is effective.

PMID- 12519550
TI  - Magnesium sulphate for preventing preterm birth in threatened preterm labour.
AB  - BACKGROUND: Magnesium sulphate is used to inhibit uterine activity in women in
      preterm labour to prevent preterm birth. OBJECTIVES: To assess the effectiveness
      and safety of magnesium sulphate therapy given to women in threatened preterm
      labour with the aim of preventing preterm birth and its sequelae. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register
      (May 2002) and the Cochrane Controlled Trials Register (The Cochrane Library,
      Issue 2, 2002). SELECTION CRITERIA:  TYPES OF PARTICIPANTS: Women thought to be
      in preterm labour. Types of interventions: Magnesium sulphate as the only
      tocolytic, administered intravenously or orally, compared with either placebo, no
      treatment or alternative tocolytic therapy. Types of outcome measures: Measures
      of effectiveness, complications, women's satisfaction with their care and health
      service use. DATA COLLECTION AND ANALYSIS: Assessments of trial eligibility,
      quality and data extractions were done by at least two of the reviewers. MAIN
      RESULTS: Over 2000 women were recruited into the 23 included trials. Only nine
      trials were rated of high quality for the concealment of allocation. In the
      magnesium sulphate versus control (all studies) no difference was seen for the
      risk of birth within 48 hours of treatment for women given magnesium sulphate
      compared with controls when using a random effects model (relative risk (RR)
      0.85, 95% confidence interval (CI) 0.58-1.25, 11 trials, 881 women). No benefit
      was seen for magnesium sulphate on the risk of giving birth preterm (<37 weeks)
      or very preterm (<34 weeks). The risk of death (fetal and paediatric) was higher
      for infants exposed to magnesium sulphate (RR 2.82, 95% CI 1.20-6.62, 7 trials,
      727 infants). There were only two fetal deaths, both in the magnesium sulphate
      group in one study. The six other trials reported there were no fetal deaths. No
      differences for total paediatric mortality were shown in the six trials with
      data. No beneficial effect was seen from using magnesium sulphate on the risk of
      other neonatal morbidity. A non-significant reduction in the risk of cerebral
      palsy was reported at follow up at 18 months corrected age (RR 0.14, 95% CI 0.01
      2.60, 1 trial, 99 children). REVIEWER'S CONCLUSIONS: Magnesium sulphate is
      ineffective at delaying birth or preventing preterm birth, and its use is
      associated with an increased mortality for the infant. Any further trials should
      be of high quality, large enough to assess serious morbidity and mortality,
      compare different dose regimens, and provide neurodevelopmental status of the
      child.

PMID- 12519551
TI  - Antibiotics for persistent nasal discharge (rhinosinusitis) in children.
AB  - BACKGROUND: Nasal discharge (rhinosinusitis) is extremely common in children. It
      is the result of inflammation of the mucosa of the upper respiratory tract, and
      is usually due to either infection or allergy. OBJECTIVES: To determine the
      effectiveness of antibiotics versus placebo or standard therapy in treating
      children with persistent nasal discharge (rhinosinusitis) for at least 10 days.
      SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE, EMBASE, and
      the references of relevant articles were searched. Authors and pharmaceutical
      companies were contacted. Date of most recent searches: February 2002. SELECTION
      CRITERIA: All randomised controlled trials that compared antibiotics versus
      placebo or standard therapy. Trials which included the use of other medications
      were included if all participants were allowed equal access to such medications
      or if the additional or alternative therapies were regarded as ineffective.
      Trials that only combined or compared antibiotics with surgery, or sinus puncture
      and lavage, were not included in the review. DATA COLLECTION AND ANALYSIS: Data
      were extracted by a single reviewer for the following eight outcomes: overall
      clinical failure (primary outcome), failure to cure, failure to improve, clinical
      improvement, time to resolution, complications, side-effects and bacteriologic
      failure. For the dichotomous outcome variables of each individual study,
      proportional and absolute risk reductions were calculated using a modified
      intention-to-treat analysis. The summary weighted risk ratio and 95% confidence
      interval (fixed effects model) were calculated using the inverse of the variance
      of each study result for weighting (Cochrane statistical package, REVMAN version
      4.1). MAIN RESULTS: A total of six studies involving 562 children compared
      antibiotics with placebo or standard therapy. Only the primary outcome (overall
      clinical failure) was reported in all studies. Around 40% of all randomised
      children did not have a clinical success documented when reviewed two to six
      weeks after randomisation. The control event rate varied from to 22 to 71% (mean
      46%). The risk ratio estimated using a fixed effects model was 0.75 (95% CI 0.61
      to 0.92). There was no evidence of statistical heterogeneity. Side effects
      occurred in 4 of 189 control group children (four studies). More children treated
      with antibiotics had side effects (17 of 330), but this difference was not
      statistically significant (RR 1.75, 95% CI 0.63 to 4.82). REVIEWER'S CONCLUSIONS:
      For children with persistent nasal discharge or older children with
      radiographically confirmed sinusitis, the available evidence suggests that
      antibiotics given for 10 days will reduce the probability of persistence in the
      short to medium-term. The benefits appear to be modest and around eight children
      must be treated in order to achieve one additional cure (NNT 8, 95% CI 5 to 29).
      No long term benefits have been documented. These conclusions are based on a
      small number of small randomised controlled trials and may require revision as
      additional data become available.

PMID- 12519552
TI  - Interventions for treating melioidosis.
AB  - BACKGROUND: Melioidosis is an infectious disease that occurs in tropical regions,
      particularly in Thailand. It is caused by the bacterium Burkholderia pseudomallei
      and is a serious condition which can be fatal. Beta-lactam antibiotics have
      dramatically reduced the risk of death, but mortality still remains high.
      OBJECTIVES: To summarize reliable evidence on the effects of treatment regimens
      on death and relapse. SEARCH STRATEGY: We searched the Cochrane Infectious
      Diseases Group trials register (July 2002), the Cochrane Controlled Trials
      Register (Issue 3, 2002), MEDLINE (1966 to July 2002), EMBASE (1980 to May 2002),
      BIOSIS (up to July 2002), Health Star (up to July 2002), and reference lists of
      articles. We also contacted pharmaceutical companies and researchers in the
      field. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials
      comparing antibiotic regimens in people with melioidosis. DATA COLLECTION AND
      ANALYSIS: We independently assessed the eligibility of studies and the
      methodological quality of the trials. Adverse effects information was collected
      from the trials. MAIN RESULTS: Nine trials, all from Thailand, involving a total
      of 872 participants were included. For intravenous therapy in the acute phase, we
      identified six trials with a total of 619 participants. Chloramphenicol,
      doxycycline, and co-trimoxazole (trimethoprim-sulphamethoxazole) combination
      regimens were associated with a mortality of 50% or more (two studies).
      Participants randomized to regimens including ceftazidime were more likely to
      survive (relative risk [RR] 0.46; 95% confidence interval [CI] 0.30 to 0.71).
      When ceftazidime-containing regimens were compared with beta-lactam or
      alternative beta-lactamase inhibitor regimens such as co-amoxiclav (amoxycillin
      clavulanic acid) and cefoperazone-sulbactam, or with imipenem, mortality rates
      were similar (RR 1.06; 95% CI 0.81 to 1.39). For oral therapy in the maintenance
      phase, we found three trials of 253 participants. They compared the conventional
      regimen (chloramphenicol, doxycycline, and trimethoprim-sulphamethoxazole) with
      other regimens (amoxycillin-clavulanic acid, ciprofloxacin-azithromycin, and
      doxycycline alone). There were fewer deaths with the conventional regimen, but no
      statistically significant differences demonstrated. REVIEWER'S CONCLUSIONS:
      Regimens for the acute phase of illness should contain ceftazidime or imipenem.
      It is not yet clear if combinations of treatments in the early phase reduce
      relapse. For oral therapy after the acute phase of treatment, trials suggest that
      conventional four drug regimens can be used for treatment.

PMID- 12519553
TI  - School-based programmes for preventing smoking.
AB  - BACKGROUND: Smoking rates in adolescents are rising. Helping young people to
      avoid starting smoking is a widely endorsed goal of public health, but there is
      uncertainty about how to do this. Schools provide a route for communicating with
      a large proportion of young people, and school-based programmes for smoking
      prevention have been widely developed and evaluated. OBJECTIVES: To review all
      randomised controlled trials of behavioural interventions in schools to prevent
      children (aged 5 to12) and adolescents (aged 13 to18) starting smoking. SEARCH
      STRATEGY: We searched The Cochrane Controlled Trials and Tobacco Review group
      registers, MEDLINE, EMBASE, Psyclnfo, ERIC, CINAHL, Health Star, Dissertation
      Abstracts and studies identified in the bibliographies of articles. Individual
      MEDLINE searches were made for 133 authors who had undertaken randomised
      controlled trials in this area. SELECTION CRITERIA: Types of studies: those in
      which individual students, classes, schools, or school districts were randomised
      to the intervention or control groups and followed for at least six months. TYPES
      OF PARTICIPANTS: Children (aged 5 to12) or adolescents (aged 13 to18) in school
      settings. Types of interventions: Classroom programmes or curricula, including
      those with associated family and community interventions, intended to deter use
      of tobacco. We included programmes or curricula that provided information, those
      that used social influences approaches, those that taught generic social
      competence, and those that included interventions beyond the school into the
      community. We included programmes with a drug or alcohol focus if outcomes for
      tobacco use were reported. Types of outcome measures: Prevalence of non-smoking
      at follow-up among those not smoking at baseline. We did not require biochemical
      validation of self-reported tobacco use for study inclusion. DATA COLLECTION AND
      ANALYSIS: We assessed whether identified citations were randomised controlled
      trials. We assessed the quality of design and execution, and abstracted outcome
      data. Because of the marked heterogeneity of design and outcomes, we did not
      perform a meta-analysis. We synthesised the data using narrative systematic
      review. We grouped studies by intervention method (information; social
      competence; social influences; combined social influences/social competence and
      multi-modal programmes). Within each category, we placed them into three groups
      according to validity using quality criteria for reported study design. MAIN
      RESULTS: Of the 76 randomised controlled trials identified, we classified 16 as
      category one (most valid). There were no category one studies of information
      giving alone. There were fifteen category one studies of social influences
      interventions. Of these, eight showed some positive effect of intervention on
      smoking prevalence, and seven failed to detect an effect on smoking prevalence.
      The largest and most rigorous study, the Hutchinson Smoking Prevention Project,
      found no long-term effect of an intensive 8-year programme on smoking behaviour.
      There was a lack of high quality evidence about the effectiveness of combinations
      of social influences and social competence approaches. There was limited evidence
      about the effectiveness of multi-modal approaches including community
      initiatives. REVIEWER'S CONCLUSIONS: There is no rigorous test of the effects of
      information giving about smoking. There are well-conducted randomised controlled
      trials to test the effects of social influences interventions: in half of the
      group of best quality studies those in the intervention group smoke less than
      those in the control, but many studies showed no effect of the intervention.
      There is a lack of high-quality evidence about the effectiveness of combinations
      of social influences and social competence interventions, and of multi-modal
      programmes that include community interventions.

PMID- 12519554
TI  - Selective serotonin reuptake inhibitors for premenstrual syndrome.
AB  - BACKGROUND: Severe premenstrual syndrome affects between 3-5% of women of
      reproductive age. Such severe PMS is classified under the Diagnostic and
      Statistical Manual of Mental Disorders as premenstrual dysphoric disorder, PMDD.
      Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used as a
      front-line therapy for premenstrual syndrome (PMS). A systematic review was
      undertaken on the efficacy of SSRIs in the management of severe PMS/PMDD, to
      assess the evidence for this treatment option. OBJECTIVES: The objective of this
      review was to evaluate the effectiveness of SSRIs in reducing premenstrual
      syndrome symptoms in women diagnosed with severe premenstrual syndrome. SEARCH
      STRATEGY: Electronic searches for relevant randomised controlled trials of the
      Cochrane Menstrual Disorders and Subfertility Group specialised register of
      controlled trials, Cochrane Controlled Trials Register, MEDLINE, EMBASE and
      PsychLit were undertaken. References were searched interactively to identify
      missed trials. Where insufficient data were presented original authors were
      contacted for further details. SELECTION CRITERIA: All trials were considered in
      which women with a prospective diagnosis of PMS/ PMDD were randomised to receive
      SSRIs or placebo in a double blind trial for the treatment of premenstrual
      syndrome. DATA COLLECTION AND ANALYSIS: 31 randomised controlled trials were
      identified which reported the use of SSRIs in the management of PMS. 16 trials
      were excluded, 15 trials were included in the systematic review, and ten trials
      were included in the main analyses. The reviewers extracted the data
      independently and standardised mean differences for continuous outcomes were
      estimated from the data. MAIN RESULTS: The primary analysis of reduction in
      overall symptomatology included data on 844 women with premenstrual syndrome.
      SSRIs were found to be highly effective in treating premenstrual symptoms.
      Secondary analysis showed that they were as effective in treating physical as
      well as behavioural symptoms. There was no significant difference between trials
      funded by pharmaceutical companies and those independently funded. Withdrawals
      due to side effects were 2.5 times more likely to occur in the treatment group,
      particularly at higher doses. REVIEWER'S CONCLUSIONS: There is now very good
      evidence to support the use of selective serotonin reuptake inhibitors in the
      management of severe premenstrual syndrome.

PMID- 12519555
TI  - Laparoscopic surgery for subfertility associated with endometriosis.
AB  - BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in
      sites other than the uterine cavity. It is variable in both its surgical
      appearance and clinical manifestation often with poor correlation between the
      two. Surgical treatment of endometriosis aims to remove visible areas of
      endometriosis and restore anatomy by division of adhesions. OBJECTIVES: To assess
      the efficacy of laparoscopic surgery in the treatment of subfertility associated
      with endometriosis. The review aims to compare outcomes of laparoscopic surgical
      interventions compared to no treatment or medical treatment with regard to
      improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders
      and Subfertility Group's specialised register of trials (searched Feb 2000), the
      Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2000),
      MEDLINE (1966-July 2001), EMBASE (1980-July 2001), the National Research Register
      (Issue 1, 2000) and reference lists of articles. SELECTION CRITERIA: Trials were
      selected if they were randomised and compared the effectiveness of laparoscopic
      surgery in the treatment of subfertility associated with endometriosis versus
      other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies
      had data appropriate for inclusion within the review. These studies compared
      laparoscopic surgical treatment of minimal and mild endometriosis compared with
      diagnostic laparoscopy only. The recorded outcomes included live birth,
      pregnancy, fetal losses and complications of surgery. MAIN RESULTS: Meta-analysis
      of the two randomised trials show improvement in infertility associated with
      endometriosis with laparoscopic surgery. The largest trial (Marcoux 1997) clearly
      supports this outcome with an increased chance of pregnancy (OR 2.03, 95% CI 1.28
      to 3.24) and ongoing pregnancy rate after 20 weeks (OR 1.95, 95% CI 1.18 to 3.22)
      but the smaller trial (Gruppo Italiano 1999) does not show benefit (pregnancy OR
      0.76, 95% CI 0.31 to 1.88; livebirth OR 0.85, 95% CI 0.32 to 2.28). Combining
      ongoing pregnancy and live birth rates there was a statistically significant
      increase with surgery (OR 1.64, 95% CI 1.05 to 2.57). REVIEWER'S CONCLUSIONS: The
      use of laparoscopic surgery in the treatment of minimal and mild endometriosis
      may improve success rates. The relevant trials have some methodological problems
      and further research in this area is needed.

PMID- 12519556
TI  - Interventions for toxic epidermal necrolysis.
AB  - BACKGROUND: Toxic epidermal necrolysis is a rare condition where a drug reaction
      induces skin loss, similar to that seen in extensive burns. It is associated with
      high morbidity and mortality and there is no clear agreement on effective
      treatment. OBJECTIVES: To assess the effects of all interventions for the
      treatment of toxic epidermal necrolysis. SEARCH STRATEGY: We searched the
      Cochrane Skin Group Specialised Register (March 2001), the Cochrane Controlled
      Trials Register (March 2001), MEDLINE (1966 to December 2001), EMBASE (1980 to
      December 2001), DARE (4th Quarter 2001) and CINAHL (1982 to October 2001).
      SELECTION CRITERIA: Randomised controlled trials of therapeutic and supportive
      interventions that included participants clinically diagnosed with toxic
      epidermal necrolysis were included. DATA COLLECTION AND ANALYSIS: Two independent
      reviewers carried out study selection and assessment of methodological quality.
      MAIN RESULTS: Only one randomised controlled trial of treatment was identified.
      This trial compared the effectiveness of thalidomide with placebo and included 22
      patients, 12 in the treatment group and 10 in the placebo group. Patients on the
      treatment arm received thalidomide 200 mg twice daily for 5 days. The main end
      point was the measurement of the progression of skin detachment after 7 days.
      Other end points were the overall mortality and severity of the disease evaluated
      with the simplified acute physiology score. The study was terminated as the
      mortality on the treatment arm was 83% compared to 30% on the control arm
      (relative risk 2.78, 95% confidence interval 1.04 to 7.40). No randomised
      controlled trials of the most commonly used current treatments i.e. systemic
      steroids, cyclosporin A and intravenous immunoglobulins were found. REVIEWER'S
      CONCLUSIONS: Treatment with thalidomide was not shown to be effective and was
      associated with significantly higher mortality than placebo. There is no reliable
      evidence on which to base treatment for toxic epidermal necrolysis, a disease
      commonly associated with mortality rates of around 30%. More research is required
      to understand the mechanisms of toxic epidermal necrolysis. International multi
      centre studies are needed in the form of randomised controlled trials, to
      evaluate treatments for toxic epidermal necrolysis, especially those using high
      doses of steroid and intravenous immunoglobulins.

PMID- 12519557
TI  - Drugs for treatment of very high blood pressure during pregnancy.
AB  - BACKGROUND: Very high blood pressure during pregnancy poses a serious threat to
      women and their babies. The use of drugs to lower blood pressure will reduce this
      risk for the women, and possibly also for the baby. OBJECTIVES: The objective of
      this review was to compare different antihypertensive drugs used for treatment of
      severe hypertension during pregnancy. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register (April 2002), the Cochrane
      Controlled Trials Register (The Cochrane Library, Issue 2 2002) and MEDLINE
      (April 2002). SELECTION CRITERIA: Studies were randomised trials. Quasi random
      designs were excluded. Participants were women with severe hypertension during
      pregnancy. Women postpartum at trial entry were excluded. Interventions were any
      comparisons of one antihypertensive agent with another. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by two reviewers to assess
      eligibility and describe the trial characteristics, and by one reviewer for the
      meta-analyses. Discrepancies were resolved by discussion. There was no blinding
      of authorship or results. Whenever possible, unpublished data were sought from
      investigators. MAIN RESULTS: Twenty trials were included (1637 women) and 19 were
      excluded. There were ten different comparisons. Hydralazine was the most common
      drug for others to be evaluated against. Diazoxide, given as 75mg bolus
      injections, appears to be associated with maternal hypotension requiring
      treatment, and ketanserin is less effective than hydralazine at reducing blood
      pressure. There is no other clear evidence that any one of the other
      antihypertensive agents is better than another for women with severe hypertension
      during pregnancy. REVIEWER'S CONCLUSIONS: Until better evidence is available, the
      choice of antihypertensive should depend on the experience and familiarity of an
      individual clinician with a particular drug, and on what is known about adverse
      maternal and fetal side-effects. Exceptions are diazoxide and ketanserin, which
      are probably not good choices.

PMID- 12519558
TI  - Surgery for varicose veins: use of tourniquet.
AB  - BACKGROUND: Varicose vein surgery is a common surgical procedure but there is no
      consensus regarding the best surgical technique. The use of tourniquets during
      varicose vein surgery has been advocated as a means of reducing the potential for
      blood loss during the operation. OBJECTIVES: To identify whether the use of a
      tourniquet should be recommended when undertaking surgery for the management of
      primary varicose veins. SEARCH STRATEGY: The reviewers searched the Cochrane
      Peripheral Vascular Diseases Group trials register (last searched November 2001),
      thirteen electronic bibliographic databases, including the Cochrane Controlled
      Trials Register (CCTR) (last searched Issue 3, 2001), covering biomedical
      science, social science, health economic and grey literature (including current
      research). In addition, the reference lists of relevant articles were checked and
      various health services research related resources were consulted via the
      Internet. These included health economics and HTA organisations, guideline
      producing agencies, generic research and trials registers, and specialist sites.
      SELECTION CRITERIA: All studies described as randomised controlled trials that
      examined the use of tourniquets during surgery for patients with primary varicose
      veins were included. DATA COLLECTION AND ANALYSIS: Data from eligible studies
      were extracted and summarised independently by two reviewers. All studies were
      cross-checked independently by the reviewers. MAIN RESULTS: A total of twenty
      published papers and nineteen studies were identified. Only three of these were
      randomised controlled trials and were included in the review. Sixteen studies
      were excluded as they were non-randomised and one was a duplicate study. All
      three trials had a small sample size and reported the trial design, outcome
      measures and analysis poorly. There were also variations in the outcome measures
      used between the trials. In addition, there was no consistency on the reporting
      of mean and medians for blood loss during the operation. It was therefore not
      possible to pool the data to perform meta-analysis. However, the reported blood
      loss when using a tourniquet was between 0 and 16mls compared to between 107 to
      133mls when not using a tourniquet (p<0.01). REVIEWER'S CONCLUSIONS: Although
      there were significant quality issues with the available evidence, the use of a
      tourniquet would appear to reduce blood loss during surgery. There were no
      reported differences between the use or non-use of a tourniquet in terms of
      complications and morbidity. However, the available trials were not of sufficient
      size to detect rarer complications such as nerve damage.

PMID- 12519559
TI  - Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition
      characterised by progressive airflow limitation that is at most partially
      reversible. Despite the lack of reversibility patients often report symptomatic
      improvement with short-acting beta-2 bronchodilator medication. Short-acting beta
      2 bronchodilators are used in the management of both stable and acute
      exacerbations of COPD. OBJECTIVES: To determine the clinical effectiveness and
      assess the adverse effects of regular treatment with short-acting beta-2 agonists
      bronchodilators in patients with stable COPD. SEARCH STRATEGY: A search was
      carried out using the Cochrane Airways Group database. In addition, the reference
      lists of review articles and the randomised controlled trials (RCTs) retrieved in
      full text were searched for other potentially relevant citations. SELECTION
      CRITERIA: RCTs of at least one week in duration comparing treatment with inhaled
      short-acting beta-2 agonists with placebo in patients with stable COPD. DATA
      COLLECTION AND ANALYSIS: Data extraction and study quality assessment was
      performed independently by two reviewers. Where further or missing data was
      required, authors of studies were contacted. The data was analysed using the
      Cochrane Review Manager 4.1. MAIN RESULTS: Thirteen studies were included in this
      review. All studies used a crossover design and were of high quality. Spirometry
      performed at the end of the study period and after the administration of
      treatment (post-bronchodilator) showed a slight but significant increase in FEV1
      and FVC when compared to placebo (WMD=0.14 L; 95%CI=0.04,0.25 & WMD=0.30 L;
      95%CI=0.02,0.58, respectively). In addition, both morning and evening PEFR were
      significantly better during active treatment than during placebo (WMD=29.17
      L/min; 95%CI=0.25,58.09 & WMD=36.75 L/min; 95%CI=2.56,70.94, respectively). A
      significant improvement in daily breathlessness score was observed during
      treatment with beta-2 agonist when compared to placebo (SMD=1.33;
      95%CI=1.0,1.65). The risk of dropping out of the study (treatment failure) when
      on treatment with placebo was almost twice that of patients on treatment with
      beta-2 agonists (RR=0.49; 95%CI=0.33,0.73). Patients preferred beta-2 agonists
      almost 10 times more frequently to placebo (OR=9.04; 95%CI=4.64,17.61). One study
      that used a validated questionnaire for 'quality of life' assessment, found
      highly significant improvements in the scores for dyspnoea (p=0.003) and fatigue
      (p=0.0003) during treatment with salbutamol. No studies reported serious side
      effects during treatment with inhaled beta-agonists. However, none of the studies
      were of sufficient length or size in order to allow any meaningful information on
      long-term occurrence of side effects. REVIEWER'S CONCLUSIONS: Use of short-acting
      beta-2 agonists on a regular basis for at least seven days in stable COPD is
      associated with improvements in post bronchodilator lung function and a decrease
      in breathlessness. Patients are far more likely to prefer treatment with beta-2
      agonists than placebo, and less likely to drop out from such treatment. None of
      the studies included in this review reported sufficient data or were of
      sufficient length or size in order to provide reliable information on adverse
      effects. Therefore large scale, parallel, longer term studies would be needed to
      investigate the effect of treatment with regular inhaled beta-2 agonists on
      mortality, disease progression and side effects. Newer, long acting
      bronchodilators (including long-acting beta-2 agonists) are currently available
      and they may be more practical and/or effective in these patients. However, this
      review indicates that treatment with these older, inexpensive drugs is beneficial
      in patients with COPD.

PMID- 12519560
TI  - Local corticosteroid injection for carpal tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome is a clinical syndrome manifested by signs and
      symptoms of irritation of the median nerve at the level of the carpal tunnel in
      the wrist. Local corticosteroid injection for carpal tunnel syndrome has been
      studied but its effectiveness and duration of benefit of local corticosteroid
      injection for Carpal tunnel syndrome remain unknown. OBJECTIVES: To evaluate the
      effectiveness of local steroid injection for carpal tunnel syndrome versus
      placebo injection or other non-surgical interventions in improving clinical
      outcome and to determine the length of symptom relief. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group register (searched June 2002),
      MEDLINE (searched January 1966 to May 2002), EMBASE (searched January 1980 to May
      2002)and CINAHL(searched January 1982 to May 2002). SELECTION CRITERIA: We
      included randomized or quasi-randomized studies of participants with carpal
      tunnel syndrome treated with local corticosteroid injection. The primary outcome
      measure was clinical improvement. DATA COLLECTION AND ANALYSIS: Three reviewers
      independently selected the trials to be included rated for their overall quality.
      Relative risks and 95% confidence intervals were calculated for each trial and
      summary relative risks and 95% confidence intervals were also calculated. MAIN
      RESULTS: We identified nine randomized controlled trials. Four were excluded. One
      trial demonstrated clinical improvement of carpal tunnel syndrome at one month
      following local corticosteroid compared to placebo injection (Relative risk 3.83
      (95% confidence intervals 1.82 to 8.05)). One trial compared local corticosteroid
      injection to oral steroid and at three months after treatment there was a
      significant improvement in the injection group (mean difference -7.00 (95%
      confidence intervals -11.58 to -2.42)). In one trial the rate of improvement
      after one month was greater after local than systemic corticosteroid injection
      (Relative risk 3.17(95% confidence intervals 1.02 to 9.87)). In one trial
      symptoms did not improve significantly for the injection group at eight weeks
      after injection compared to treatment with anti-inflammatory medication and
      splinting (mean difference 0.10 (95% confidence intervals -0.33 to 0.53)).
      Although local steroid injection did provide benefit compared to Helium-Neon
      Laser treatment at two weeks after onset of treatment (Relative risk 0.27 (95% CI
      0.09 to 0.83), this effect did not hold at six months follow-up (Relative risk
      0.76 (95% confidence intervals 0.48 to 1.21). REVIEWER'S CONCLUSIONS: Local
      corticosteroid injection for carpal tunnel syndrome provides greater clinical
      improvement in symptoms one month after injection compared to placebo. Symptom
      relief beyond one month compared to placebo has not been demonstrated. Local
      corticosteroid injection provides significantly greater clinical improvement
      compared to oral steroid up to three months after treatment. Local corticosteroid
      injection does not provide improved clinical outcome compared to either anti
      inflammatory treatment and splinting after eight weeks or Helium -Neon laser
      treatment after six months.

PMID- 12519561
TI  - Remacemide for drug-resistant localization related epilepsy.
AB  - BACKGROUND: Epilepsy is a common neurological condition, affecting 0.5 to 1% of
      the population. Nearly 30 per cent of people with epilepsy have seizures that are
      refractory to currently available drugs. In response to this problem, potential
      new drugs are being developed. Remacemide is one of these. OBJECTIVES: To
      evaluate the effects of add-on treatment with remacemide upon seizures, adverse
      effects, cognition and quality of life for people with drug-resistant
      localization related epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy
      Group trials register (4 July 2002), the Cochrane Controlled Trials Register (The
      Cochrane Library Issue 2, 2002) and MEDLINE (28 May 2002). In addition, we
      contacted AstraZeneca (makers of remacemide) and colleagues in the field to see
      if they were aware of any trials that we had missed. SELECTION CRITERIA:
      Randomized placebo controlled add-on trials of people of any age with
      localization related seizures, in which an adequate method of concealment of
      randomization was used. The studies could be blinded or unblinded and be of
      parallel or crossover design. They had to have a minimum treatment period of
      eight weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected
      trials for inclusion and extracted data. Any disagreements were resolved by
      discussion. Outcomes investigated included 50 per cent or greater reduction in
      seizure frequency, treatment withdrawal, adverse effects, effects on cognition
      and quality of life. The primary analyses were by intention-to-treat. Dose
      response was evaluated in regression models. MAIN RESULTS: Two parallel group
      trials were included representing 514 individuals. Daily doses of 300, 600, 800
      and 1200mg of remacemide were tested. The overall relative risk (RR) for
      remacemide versus placebo with 95% confidence intervals(CI) for a 50 per cent or
      greater reduction in seizure frequency was 1.59(95% CI 0.91 to 2.79). Due to
      differences in response rates among trials, regression models were unable to
      provide reliable estimates of responses to individual doses. Regression models
      did however suggest a significant effect for 800-1200mg remacemide per day.
      Remacemide was more likely to be withdrawn than placebo, the RR for treatment
      withdrawal was 1.90(95% CI 1.00 to 3.60). The RR for dizziness indicates that it
      is significantly associated with remacemide 3.08(99% CI 1.37 to 6.95). Effects on
      cognition and quality of life were not reported. REVIEWER'S CONCLUSIONS: Given
      the modest effect on seizure frequency and significant withdrawal rate it is
      unlikely that remacemide will be further developed as an antiepileptic drug.

PMID- 12519562
TI  - Drug management for acute tonic-clonic convulsions including convulsive status
      epilepticus in children.
AB  - BACKGROUND: Tonic-clonic (grand mal) convulsions and convulsive status
      epilepticus (currently defined as a grand mal convulsion lasting at least 30
      minutes) are medical emergencies and demand urgent and appropriate anticonvulsant
      treatment. Diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde may all
      be regarded as drugs of first choice. OBJECTIVES: To review the evidence
      comparing diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in
      treating acute tonic-clonic convulsions and convulsive status epilepticus in
      children. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's specialized
      register (4 July 2002); the Cochrane Controlled Trials Register (Cochrane Library
      Issue 2, 2002); MEDLINE (28 May 2002) and EMBASE (January 2002). SELECTION
      CRITERIA: Randomized controlled trials comparing lorazepam and other
      anticonvulsant drugs used for the treatment of convulsive status epilepticus in
      children. DATA COLLECTION AND ANALYSIS: This was a review of published, aggregate
      data. The main outcome measures included cessation of the presenting tonic-clonic
      convulsion/episode of convulsive status epilepticus; the number of additional
      drugs required to stop the convulsion; people demonstrating respiratory
      depression and people requiring admission to the intensive care unit because of
      respiratory depression. MAIN RESULTS: Only one trial was found, in which children
      were allocated lorazepam or diazepam. The main results are as follows. (1) One or
      two intravenous doses stopped the convulsion in 19 of 27 (70%) lorazepam and 22
      of the 34 (65%) intravenous diazepam-treated children. The relative risk (RR)
      with 95% confidence intervals (CIs) was 1.09(95% CI 0.77 to 1.54). A single dose
      of rectal lorazepam stopped the convulsion in six of six, compared to six of 19
      children treated with rectal diazepam, RR 3.17(95% CI 1.63 to 6.14). (2) Six of
      the 27 (22%) intravenous lorazepam and 12 of the 34 (35%) intravenous diazepam
      treated children respectively, experienced a further convulsion within 24 hours
      after presentation RR 0.63(95% CI 0.27 to 1.46). (3) Only one of 27 children (4%)
      who received intravenous lorazepam compared to five of 34 children (15%) who
      received intravenous diazepam required additional antiepileptic drugs to
      terminate the presenting seizure RR 0.25(95% CI 0.03 to 2.03). (4) A lower
      incidence of respiratory depression occurred in the lorazepam-treated group: one
      of 27 (4%) children compared to seven of 34 in the diazepam-treated group (21%),
      RR 0.21(95% CI 0.02 to 1.37). REVIEWER'S CONCLUSIONS: This review provides no
      evidence to suggest that intravenous lorazepam should be preferred to diazepam as
      the first-line drug in treating acute tonic-clonic convulsions including
      convulsive status epilepticus in children. There was some evidence from this
      review that rectal lorazepam may be more effective and safer than rectal
      diazepam, but the data were insufficient to indicate that lorazepam should
      replace diazepam as the first choice rectal drug in treating acute tonic-clonic
      convulsions and convulsive status epilepticus.

PMID- 12519563
TI  - Oral or topical nasal steroids for hearing loss associated with otitis media with
      effusion in children.
AB  - BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss
      with associated developmental delay. Treatment remains controversial. The
      effectiveness of both systemic and topical intranasal steroids in promoting the
      resolution of effusions has been assessed by randomised controlled trials.
      OBJECTIVES: To examine evidence for or against treating children with hearing
      loss associated with OME with systemic or topical intranasal steroids. SEARCH
      STRATEGY: Searches were conducted in January 2002. We searched the Cochrane
      Controlled Trials Register using the terms 'otitis media', 'otitis media with
      effusion', 'glue ear', or 'OME', and 'steroids', 'glucocorticoids, synthetic',
      'glucocorticoids, topical', 'anti-inflammatory agents, steroidal'. EMBASE and
      MEDLINE were also searched for additional information. SELECTION CRITERIA:
      Randomised controlled trials of oral and topical intranasal steroids, either
      alone or in combination with another agent such as an antibiotic, were included.
      EXCLUSIONS: publications in abstract form only since adequate appraisal was not
      possible; uncontrolled, non-randomised or retrospective studies; studies
      reporting outcomes with ears (rather than children) as the unit of analysis
      unless data were of sufficient detail to allow analysis by child. DATA COLLECTION
      AND ANALYSIS: Data were extracted from the published reports by the two authors
      independently (CCB and JH van der V) using standardised data extraction forms and
      methods. The methodological quality of the included studies was independently
      assessed by the two authors using the scheme described in the Cochrane Handbook.
      Dichotomous results were expressed as an odds ratio using a fixed effects model
      together with the 95% confidence intervals. Continuous data were analysed using
      the weighted mean difference in a fixed effects model. Tests for heterogeneity
      between studies were performed using a Mantel-Haenszel approach. In trials with a
      cross over design, post crossover treatment data were not used. MAIN RESULTS: No
      study prospectively documented hearing loss associated with OME prior to
      randomisation. Follow up was mainly short term. No serious or lasting adverse
      effects were reported in the six studies that did mention adverse effects. Most
      comparisons involved small numbers of subjects. The odds ratio for OME persisting
      after short term follow up in children treated with oral steroids compared to
      control was 0.22 (95% CI 0.08 to 0.63). The odds ratio for OME persisting after
      short term follow up for children treated with oral steroids plus antibiotic
      compared to control plus antibiotic was 0.32 (95% CI 0.20 to 0.52). However there
      was significant heterogeneity between studies included in the latter comparison
      (p<0.01). Trends favoured steroids for most other comparisons, but confidence
      intervals included unity. There was no evidence of benefit for steroid treatment
      for resolution of OME or of resolution of hearing loss associated with OME in the
      longer term. REVIEWER'S CONCLUSIONS: Both oral and topical intranasal steroids
      alone or in combination with an antibiotic lead to a quicker resolution of OME in
      the short term. However, there is no evidence of a long term benefit from
      treating OME effusions or associated hearing loss with either oral or topical
      intranasal steroids. No serious adverse events were reported in the six studies
      that presented data on adverse effects. Future studies should document hearing
      loss associated with OME before the start of study treatment. Follow up should be
      longer and ideally include health related quality of life and hearing
      assessments. Data should not be presented only with ears as the unit of analysis.

PMID- 12519564
TI  - Vitamin A supplementation during pregnancy.
AB  - BACKGROUND: Vitamin A supplements have been recommended in pregnancy to improve
      outcomes that include maternal mortality and morbidity. OBJECTIVES: To review the
      effectiveness of vitamin A supplementation during pregnancy, alone or in
      combination with other supplements, on maternal and newborn clinical and
      laboratory outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's specialised register of controlled trials (April 2002) and the
      Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2002).
      SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating the
      effect of vitamin A supplementation in pregnant women. The types of intervention
      included vitamin A supplementation alone or in combination with other micro
      nutrients. DATA COLLECTION AND ANALYSIS: We assessed trials for methodological
      quality using the standard Cochrane criteria of adequacy of concealment. At least
      two reviewers independently assessed the trials for inclusion and extracted data.
      We collected information on blinding, loss to follow-up, setting, number of
      women, exclusion after randomisation and follow-up as well as supplementation
      type, dose and frequency. The outcomes we sought included maternal and neonatal
      clinical and laboratory outcomes. MAIN RESULTS: Five trials involving 23,426
      women were included. Because the trials were heterogeneous with regard to type of
      supplement given, duration of supplement use and outcomes measured, pooled
      results using meta analysis could not be performed. One large population based
      trial in Nepal showed a possible beneficial effect on maternal mortality after
      weekly vitamin A supplements. In this study a reduction was noted in all cause
      maternal mortality up to 12 weeks postpartum with Vitamin A supplementation (RR
      0.60, 95% CI 0.37-0.97). Night-blindness was assessed in a nested case-control
      study within this trial and found to be reduced but not eliminated. Three trials
      examined the effect of vitamin A supplementation on haemoglobin levels. The trial
      from Indonesia showed a beneficial effect in women who were anaemic ([Hb] <11.0
      g/dl). After supplementation, the proportion of women who became non-anaemic was
      35% in the Vitamin A supplemented group, 68% in the iron-supplemented group, 97%
      in the group supplemented with both Vitamin A and iron and 16% in the placebo
      group. The two trials from Malawi did not corroborate these positive findings.
      REVIEWER'S CONCLUSIONS: Although the two trials from Nepal and Indonesia
      suggested beneficial effects of vitamin A supplementation, further trials are
      needed to determine whether vitamin A supplements can reduce maternal mortality
      and morbidity and by what mechanism.

PMID- 12519565
TI  - Anticoagulation for cerebral sinus thrombosis.
AB  - BACKGROUND: Treatment of cerebral sinus thrombosis with anticoagulants has been
      controversial. Anticoagulants may prevent new venous infarcts, neurologic
      deterioration, and pulmonary embolism but may also promote haemorrhages.
      OBJECTIVES: To review the available evidence regarding the effectiveness and
      safety of anticoagulant therapy in patients with confirmed cerebral sinus
      thrombosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials
      Register (last searched 18 March 2002). We also searched MEDLINE (1966-Oct 2001),
      EMBASE (1980-Feb 2002) and the Cochrane Controlled Trials Register (Cochrane
      Library, 2002 Issue 1) and contacted authors to identify additional published and
      unpublished studies. SELECTION CRITERIA: Unconfounded randomised controlled
      trials in which anticoagulant therapy was compared with placebo or open control
      in patients with cerebral sinus thrombosis (confirmed by intra-arterial contrast
      or magnetic resonance angiography). DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted outcomes for each of the two treatment groups
      (anticoagulant treatment and control). The outcome data for each patient are
      analysed in the treatment group to which the patient was originally allocated
      ('intention to treat' analysis). A weighted estimate of the treatment effects
      across trials (relative risk, absolute risk reduction) is calculated using the
      Cochrane statistical software. MAIN RESULTS: Two small trials involving 79
      patients fulfilled the inclusion criteria. One trial (20 patients) examined the
      efficacy of intravenous, adjusted dose unfractionated heparin. The other trial
      (59 patients) examined high dose, body weight adjusted, subcutaneous, low
      molecular weight heparin (Nadroparin). Anticoagulant therapy was associated with
      a pooled relative risk of death of 0.33 (95 % CI 0.08 to 1.21) and of death or
      dependency of 0.46 (95 % CI 0.16 to 1.31). No new symptomatic intracerebral
      haemorrhages were observed. One major gastro-intestinal haemorrhage occurred
      after anticoagulant treatment. Two control patients (placebo) had a diagnosis of
      probable pulmonary embolism (one fatal). REVIEWER'S CONCLUSIONS: Based upon the
      limited evidence available, anticoagulant treatment for cerebral sinus thrombosis
      appeared to be safe and was associated with a potentially important reduction in
      the risk of death or dependency which did not reach statistical significance.

PMID- 12519566
TI  - Nystatin prophylaxis and treatment in severely immunodepressed patients.
AB  - BACKGROUND: Nystatin is sometimes used prophylactically in patients with severe
      immunodeficiency or in the treatment of fungal infection in such patients,
      although the effect seems to be equivocal. OBJECTIVES: To study whether nystatin
      decreases morbidity and mortality when given prophylactically or therapeutically
      to patients with severe immunodeficiency. SEARCH STRATEGY: MEDLINE and The
      Cochrane Library using a comprehensive search strategy, date of last search
      November 2001. Contacted industry and scanned reference lists. SELECTION
      CRITERIA: Randomised trials comparing nystatin with placebo, an untreated control
      group, fluconazole or amphotericin B. DATA COLLECTION AND ANALYSIS: Data on
      mortality, invasive fungal infection and colonisation were extracted by both
      authors independently. A random effects model was used unless p>0.10 for the test
      of heterogeneity. MAIN RESULTS: We included 12 trials (1,464 patients). The drugs
      were given prophylactically in ten trials and as treatment in two. Seven trials
      were in acute leukaemia, two in cancer, one in liver transplant patients, one in
      critically ill surgical and trauma patients, and one in AIDS patients. Nystatin
      had been compared with placebo in three trials and with fluconazole in nine; the
      dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was similar to
      that of placebo on fungal colonisation (relative risk 0.85, 95% confidence
      interval 0.65 to 1.13). There was no statistically significant difference between
      fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas
      fluconazole was more effective in preventing invasive fungal infection (relative
      risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70). The
      results were very similar if the three studies which were not performed in cancer
      patients were excluded. REVIEWER'S CONCLUSIONS: Nystatin cannot be recommended
      for prophylaxis or treatment of Candida infections in immunodepressed patients.

PMID- 12519567
TI  - Speech and language therapy for dysarthria due to non-progressive brain damage.
AB  - BACKGROUND: Dysarthria is a common sequel of non-progressive brain damage
      (typically stroke and traumatic brain damage). Impairment-based therapy and a
      wide variety of compensatory management strategies are undertaken by speech and
      language therapists with this patient population. OBJECTIVES: To determine the
      efficacy of speech and language therapy interventions for adults with dysarthria
      following non-progressive brain damage. SEARCH STRATEGY: This review has drawn on
      the search strategies developed for the following Cochrane Groups as a whole:
      Stroke, Injuries, Movement Disorders and Infectious Diseases. Relevant trials
      were identified in the Specialised Registers of Controlled Trials (see Review
      Group details for more information). We also searched the trials register of the
      Cochrane Rehabilitation and Related Therapies Field. The Trials Registers were
      last searched in December 2001. The Cochrane Controlled Trials Register (Cochrane
      Library 2002, Issue 1), MEDLINE (1966-December 2001), EMBASE (1980-December
      2001), CINAHL (1983-December 2001), PsycINFO (1974-February 2002) and Linguistics
      and Language Behavior Abstracts (1983-October 2001) were searched electronically.
      We handsearched the International Journal of Language and Communication Disorders
      (1966-2002, Issue 1) and selected conference proceedings, and scanned the
      reference lists of relevant articles. Colleagues were approached to identify
      other possible published and unpublished studies. SELECTION CRITERIA:
      Unconfounded randomised controlled trials. DATA COLLECTION AND ANALYSIS: One
      reviewer assessed trial quality. Two co-reviewers were available to examine any
      potential trials for possible inclusion in the review. MAIN RESULTS: No trials of
      the required standard were identified. REVIEWER'S CONCLUSIONS: There is no
      evidence of the quality required by this review to support or refute the
      effectiveness of Speech and Language Therapy interventions for dysarthria
      following non-progressive brain damage. There is an urgent need for good quality
      research in this area.

PMID- 12519568
TI  - Open mesh versus non-mesh for repair of femoral and inguinal hernia.
AB  - BACKGROUND: Inguinal hernia repair is the most frequent operation in general
      surgery. Until recently the standard procedure has been open musculo-aponeurotic
      repair using sutures under tension to close the defect but 'tension-free' repair
      using prosthetic mesh is becoming increasingly common in many countries.
      OBJECTIVES: The purpose of this review is to evaluate open mesh techniques in
      comparison with open non-mesh techniques for the surgical repair of groin hernia.
      SEARCH STRATEGY: Electronic databases were searched and further trials were
      sought from the reference lists of reports of known trials. Through the EU Hernia
      Trialists Collaboration authors of identified randomised controlled trials were
      asked for information on any other trials known to them. There was no language
      restriction. SELECTION CRITERIA: Studies were eligible for inclusion if they were
      randomised or quasi-randomised trials comparing either a) open mesh with open non
      mesh repair of groin hernia or b) open flat mesh repair with plug and mesh repair
      of groin hernia. DATA COLLECTION AND ANALYSIS: For each outcome the results were
      derived using data from the best available source. The majority of data for this
      review came from individual patient data (IPD) supplied by the trialists. When
      these were unavailable data came from additional aggregated information or from
      published trial reports. All trials were analysed using the 'intention to treat'
      principle. MAIN RESULTS: Twenty trials comparing open mesh with open non-mesh
      repair were identified. Open mesh methods, on average, took 7-10 minutes less to
      perform than Shouldice procedures, but took 1-4 minutes longer than other non
      mesh methods. There were no clear differences between mesh and non-mesh groups
      for haematomas, seromas or wound/superficial infections. Three serious operative
      complications were reported after open mesh repair and three following non-mesh
      repair. Overall, those in the mesh groups had a shorter length of hospital stay
      and quicker return to usual activities, but this pattern was not observed for all
      trials. There was a suggestion that persisting pain was less frequent after mesh
      repair than after non-mesh repair but this result was dependent on one trial and
      data were not available for 11 trials. There was no evidence of a difference
      between the groups with respect to persisting numbness. Fewer hernia recurrences
      were reported after mesh repair (Peto OR: 0.37, 95% CI: 0.26 to 0.51). There were
      too few data to reliably address differential effects for patients with
      recurrent, bilateral or femoral hernias. Two trials comparing flat mesh with plug
      and mesh were identified. There was no clear evidence of differences between the
      groups. REVIEWER'S CONCLUSIONS: There is evidence that the use of open mesh
      repair is associated with a reduction in the risk of recurrence of between 50%
      and 75%. Although the trials were heterogeneous there is also some evidence of
      quicker return to work and of lower rates of persisting pain following mesh
      repair.

PMID- 12519569
TI  - Buprenorphine maintenance versus placebo or methadone maintenance for opioid
      dependence.
AB  - BACKGROUND: Buprenorphine has recently been reported to be an alternative to
      methadone and LAAM for maintenance treatment of opioid dependent individuals,
      differing results are reported concerning its relative effectiveness indicating
      the need for an integrative review. OBJECTIVES: To evaluate the effects of
      buprenorphine maintenance against placebo and methadone maintenance in retaining
      patients in treatment and in suppressing illicit drug use. SEARCH STRATEGY: We
      searched the following databases up to 2001, inclusive: Cochrane Drugs and
      Alcohol Review Group Register, the Cochrane Controlled Trials Register, MEDLINE,
      EMBASE, Current Contents, Psychlit, CORK [www. state.vt.su/adap/cork], Alcohol
      and Drug Council of Australia (ADCA) [www.adca.org.au], Australian Drug
      Foundation (ADF -VIC) [www.adf.org.au], Centre for Education and Information on
      Drugs and Alcohol (CEIDA) [www.ceida.net.au], Australian Bibliographic Network
      (ABN), and Library of Congress databases, available NIDA monographs and the
      College on Problems of Drug Dependence Inc. proceedings, the reference lists of
      all identified studies and published reviews and authors of identified RCT's were
      asked about any other published or unpublished relevant RCT. SELECTION CRITERIA:
      Randomised clinical trials of buprenorphine maintenance compared with either
      placebo or methadone maintenance for opioid dependence. DATA COLLECTION AND
      ANALYSIS: Reviewers evaluated the papers separately and independently, rating
      methodological quality of concealment of allocation; data were extracted
      independently for meta-analysis and double-entered. MAIN RESULTS: Thirteen
      studies met the inclusion criteria, all were randomised clinical trials, all but
      one were double-blind. The method of concealment of allocation was not clearly
      described in 11 of the studies, otherwise methodological quality was good.
      Buprenorphine given in flexible doses appeared statistically significantly less
      effective than methadone in retaining patient in treatment (RR= 0.82; 95% CI:
      0.69-0.96). Low dose buprenorphine is not superior to low dose methadone. High
      dose buprenorphine does not retain more patients than low dose methadone, but may
      suppress heroin use better. There was no advantage for high dose buprenorphine
      over high dose methadone in retention (RR=0.79; 95% CI:0.62-1.01), and high dose
      buprenorphine was inferior in suppression of heroin use. Buprenorphine was
      statistically significantly superior to placebo medication in retention of
      patients in treatment at low doses (RR=1.24; 95% CI: 1.06-1.45), high doses
      (RR=1.21; 95% CI: 1.02-1.44), and very high doses (RR=1.52; 95% CI: 1.23-1.88).
      However, only high and very high dose buprenorphine suppressed heroin use
      significantly above placebo. REVIEWER'S CONCLUSIONS: Buprenorphine is an
      effective intervention for use in the maintenance treatment of heroin dependence,
      but it is not more effective than methadone at adequate dosages.

PMID- 12519570
TI  - Methadone maintenance therapy versus no opioid replacement therapy for opioid
      dependence.
AB  - BACKGROUND: Methadone maintenance was the first widely used form of opioid
      replacement therapy developed to treat heroin dependence, and it remains the best
      researched treatment for this problem. Despite the widespread use of methadone in
      maintenance treatment for opioid dependence in many countries, it is a
      controversial treatment whose effectiveness has been disputed. OBJECTIVES: To
      evaluate the effects of methadone maintenance treatment (MMT) compared with
      treatments that did not involve opioid replacement therapy (i.e., detoxification,
      offer of drug-free rehabilitation, placebo medication, wait-list controls) for
      opioid dependence. SEARCH STRATEGY: We searched all the following databases up to
      2001: Cochrane Drugs and Alcohol Review Group Register, the Cochrane Controlled
      Trials Register, MEDLINE, EMBASE, Current Contents, Psychlit, CORK [www.
      state.vt.su/adap/cork], Alcohol and Drug Council of Australia (ADCA)
      [www.adca.org.au], Australian Drug Foundation (ADF-VIC) [www.adf.org.au], Centre
      for Education and Information on Drugs and Alcohol (CEIDA) [www.ceida.net.au],
      Australian Bibliographic Network (ABN), and Library of Congress databases,
      available NIDA monographs and the College on Problems of Drug Dependence Inc.
      proceedings, the reference lists of all identified studies and published reviews;
      authors of identified RCTs were asked about other published or unpublished
      relevant RCTs. SELECTION CRITERIA: All randomised controlled clinical trials of
      methadone maintenance therapy compared with either placebo maintenance or other
      non-pharmacological therapy for the treatment of opioid dependence. DATA
      COLLECTION AND ANALYSIS: Reviewers evaluated the papers separately and
      independently, rating methodological quality of concealment of allocation, data
      were extracted independently for meta-analysis and double-entered. MAIN RESULTS:
      Six studies met the criteria for inclusion in this review, all were randomised
      clinical trials, two were double-blind. There were a total number of 954
      participants. The method of concealment of allocation was inadequate in one
      study, not clearly described in four studies, but adequate in a sixth study.
      Based on the meta-analysis, methadone appeared statistically significantly more
      effective than non-pharmacological approaches in retaining patient in treatment
      (3 RCTs, RR=3.05; 95%CI: 1.75-5.35) and in the suppression of heroin use (3 RCTs,
      RR=0.32; 95%CI: 0.23-0.44), but not statistically in criminal activity (3 RCTs,
      RR=0.39; 95%CI: 0.12-1.25). REVIEWER'S CONCLUSIONS: Methadone is an effective
      maintenance therapy intervention for the treatment of heroin dependence as it
      retains patients in treatment and decreases heroin use better than treatments
      that do not utilise opioid replacement therapy. It does not show a statistically
      significant superior effect on criminal activity.

PMID- 12519571
TI  - Prophylactic antibiotic administration in pregnancy to prevent infectious
      morbidity and mortality.
AB  - BACKGROUND: Some previous studies suggested that prophylactic antibiotics given
      during pregnancy improved maternal and perinatal outcomes, some did not show any
      benefit and some even reported adverse effects. OBJECTIVES: To determine the
      effect of prophylactic antibiotics during second and third trimester of pregnancy
      on maternal and perinatal outcomes. SEARCH STRATEGY: The Cochrane Pregnancy and
      Childbirth Group trials register (April 2002), the Cochrane Controlled Trials
      Register (The Cochrane Library, Issue 1, 2002) and reference lists of articles
      were searched. SELECTION CRITERIA: Randomized controlled trials comparing
      prophylactic antibiotic treatment with placebo or no treatment for women in the
      second or third trimester of pregnancy before labour. DATA COLLECTION AND
      ANALYSIS: Trial quality assessment and data extraction were done by the
      reviewers. MAIN RESULTS: There were six randomized controlled trials which
      recruited 2184 women to detect the effect of prophylactic antibiotic
      administration in the second or third trimester on pregnancy outcomes. Antibiotic
      prophylaxis in unselected pregnant women reduced the risk of prelabour rupture of
      membranes (Peto odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14 to 0.73).
      In women with a previous preterm birth there was a risk reduction in low birth
      weight (OR 0.48, 95% CI 0.27 to 0.84) and postpartum endometritis (OR 0.46, 95%
      CI 0.24 to 0.89). There was a risk reduction in preterm delivery (OR 0.48, 95% CI
      0.28 to 0.81) in pregnant women with a previous preterm birth associated with
      bacterial vaginosis (BV) during the current pregnancy but there was no risk
      reduction in pregnant women with previous preterm birth without BV during
      pregnancy (OR 1.06, 95% CI 0.68 to 1.64). However, vaginal antibiotic prophylaxis
      during pregnancy did not prevent infectious pregnancy outcomes and there is a
      possibility of adverse effects such as neonatal sepsis (OR 8.07, 95% CI 1.36 to
      47.77). REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis given during the second or
      third trimester of pregnancy reduces the risk of prelabour rupture of the
      membranes when given routinely to pregnant women. Beneficial effects on birth
      weight and the risk of postpartum endometritis were seen for high risk women.

PMID- 12519572
TI  - Plasma exchange for myasthenia gravis.
AB  - BACKGROUND: Myasthenia gravis is an autoimmune disease mediated by auto
      antibodies direct against the nicotinic receptor for acetylcholine. Patients
      would be expected to benefit from plasma exchange. Non-randomised studies suggest
      that plasma exchange is beneficial in the short term. OBJECTIVES: To examine the
      efficacy of plasma exchange in the short and long term treatment of myasthenia
      gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group
      register (searched 17 July 2002) and MEDLINE (January 1966 to June 2002) for
      randomised controlled trials using myasthenia gravis as the search term. We
      checked the bibliographies in reports of randomised trials and contacted one
      author to identify additional published or unpublished data. SELECTION CRITERIA:
      Types of studies: All randomised or quasi-randomised studies. TYPES OF
      PARTICIPANTS: All patients with myasthenia gravis who were diagnosed by an
      internationally accepted definition. Types of intervention: Treatment with plasma
      exchange alone or combined with steroids or immunosuppressive drugs. Types of
      outcome measures: PRIMARY OUTCOME MEASURE: ~bullet~patients treated for
      exacerbation: change in a specific muscle score after plasma exchange;
      ~bullet~patients treated for chronic myasthenia gravis: change in a functional
      scale. SECONDARY OUTCOME MEASURES: ~bullet~patients treated for exacerbation:
      change in a functional scale and percentage weaned from mechanical ventilation;
      ~bullet~patients treated for chronic myasthenia gravis: percentage in remission
      by the end of one year after first plasma exchange; ~bullet~adverse events. DATA
      COLLECTION AND ANALYSIS: One author extracted the data and the two others checked
      them. Since there was only one trial no formal meta-analysis was required. MAIN
      RESULTS: We identified one randomised controlled trial. Improvement in a
      quantitative muscle score was not significantly greater in patients treated with
      plasma exchange and prednisone than in patients treated with prednisone alone one
      month after onset of treatment. More relapses were observed in the plasma
      exchange and prednisone group in the first year as compared with the prednisone
      alone group. Problems in recruitment and matching of patients entered into this
      trial limit the conclusions that can be drawn. On the other hand,experience from
      many non-randomised studies suggests that plasma exchange is beneficial in
      myasthenia gravis. Consequently the relative benefits of plasma exchange are
      still unconfirmed. REVIEWER'S CONCLUSIONS: There are no adequate randomised
      controlled trials but many case series report short-term benefit from plasma
      exchange in myasthenia gravis, especially in myasthenic crisis. There are no
      adequate randomised controlled trials to determine whether plasma exchange
      improves the long-term outcome for myasthenia gravis. Further research is need to
      compare plasma exchange with alternative short-term treatments for myasthenic
      crisis and to determine the value of long-term plasma exchange for treating
      myasthenia gravis.

PMID- 12519573
TI  - Prevention of NSAID-induced gastroduodenal ulcers.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents
      in the management of arthritic and inflammatory conditions, and are among the
      most frequently prescribed medications in North America and Europe. However,
      there is overwhelming evidence linking these agents to a variety of
      gastrointestinal (GI) toxicities. OBJECTIVES: To review the effectiveness of
      common interventions for the prevention of NSAID induced upper GI toxicity.
      SEARCH STRATEGY: A literature search was conducted, according to the Cochrane
      methodology for identification of randomized controlled trials in electronic
      databases, including MEDLINE from 1966 to June 2002, Current Contents for 6
      months prior to June 2002, EMBASE to February 2002, and a search of the Cochrane
      Controlled Trials Register from 1973 to 2002. Biosis Previews(R), ADIS LMS Drug
      Alerts, Pharmaceutical News Index (PNI)(R) were searched to June 2002. New
      articles since the last search update were evaluated. Recent conference
      proceedings were reviewed and content experts and companies were contacted.
      SELECTION CRITERIA: Randomized controlled clinical trials (RCTs) of prostaglandin
      analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI)
      for the prevention of chronic NSAID induced upper GI toxicity were included. DATA
      COLLECTION AND ANALYSIS: Two independent reviewers extracted data regarding
      population characteristics, study design, methodological quality and number of
      patients with endoscopic ulcers, ulcer complications, symptoms, overall drop
      outs, drop outs due to symptoms. Dichotomous data was pooled using RevMan V4.1.
      Heterogeneity was evaluated using a chi square test. MAIN RESULTS: Forty RCTs met
      the inclusion criteria. All doses of misoprostol significantly reduced the risk
      of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day for the
      prevention of endoscopic gastric ulcers (RR=0.17, and RR=0.39 respectively,
      p=0.0055). A dose response relationship was not seen with duodenal ulcers.
      Misoprostol caused diarrhea at all doses, although significantly more at 800
      ug/day than 400 ug/day (p=0.0012). Misoprostol was the only prophylactic agent
      documented to reduce ulcer complications. Standard doses of H2RAs were effective
      at reducing the risk of endoscopic duodenal (RR=0.36; 95% CI: 0.18-0.74) but not
      gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were
      effective at reducing the risk of endoscopic duodenal and gastric ulcers
      (RR=0.44; 95% CI:0.26-0.74 and RR=0.40;95% CI;0.32-0.51 respectively for gastric
      ulcer), and were better tolerated than misoprostol. REVIEWER'S CONCLUSIONS:
      Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic
      NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol
      are less effective and are still associated with diarrhea. Only Misoprostol
      800ug/day has been directly shown to reduce the risk of ulcer complications such
      as perforation hemorrhage or obstruction.

PMID- 12519574
TI  - Nitrates for achalasia.
AB  - BACKGROUND: Achalasia is a disease that impairs oesophageal motility. Though
      nitrates have been used to treat achalasia for a long time, the effectiveness of
      nitrates for achalasia is still controversial. OBJECTIVES: To quantify short-term
      and long-term effects of nitrate therapy in patients with achalasia. SEARCH
      STRATEGY: Trials were identified by searching the Cochrane Controlled Trials
      Register (Issue 4-2001), MEDLINE (1966-2001), EMBASE (1980-2001), LILACS - Latin
      American and Caribbean health science literature (1982-2001) and CBM-Chinese
      Biomedical database(1980-2000). Additionally, all references in the identified
      trials were checked for further relevant trials. SELECTION CRITERIA: All
      randomised controlled trials involving achalasic patients given any type of
      nitrates were included. DATA COLLECTION AND ANALYSIS: Data were extracted by two
      independent observers based on the intention to treat principle. MAIN RESULTS:
      Two randomised cross-over studies were found, but no results are included. Due to
      the design of the studies and the method of reporting the results in the original
      paper it was not possible to extract the necessary information to examine any of
      the outcomes. REVIEWER'S CONCLUSIONS: We can conclude no implications for
      practice at this stage. Appropriately designed parallel group randomised
      controlled trials with long term follow-up are needed to determine the effects of
      nitrates.

PMID- 12519575
TI  - Mechanical ventilation for newborn infants with respiratory failure due to
      pulmonary disease.
AB  - BACKGROUND: Before the 1960s newborn infants with severe lung disease, usually
      due to respiratory distress syndrome (RDS), had a very high mortality rate.
      Standard treatment consisted of supportive measures including supplemental oxygen
      and correction of metabolic acidosis. Mechanical ventilation (MV) was introduced
      in the 1960s to correct hypoxaemia and respiratory acidosis in infants who were
      likely to die. MV is now standard treatment for infants with severe RDS but the
      degree to which this made a contribution to the outcome of such infants compared
      with standard neonatal care, is uncertain. OBJECTIVES: To evaluate the effects of
      the use of MV compared with no MV on mortality and morbidity in newborn infants
      with severe respiratory failure due to pulmonary disease. SEARCH STRATEGY:
      Searches were last updated in March 2002 on the Cochrane Controlled Trials
      Register (Cochrane Library Issue 1, 2002), MEDLINE from 1966 and EMBASE from
      1980. In order to detect trials that may not have been published in full,
      searches carried out of the Oxford Database of Perinatal Trials and for abstracts
      published by the Society for Pediatric Research (1967 to 2001) and the European
      Society for Pediatric Research 1970 to 1977. Experts were consulted with emphasis
      on those who were in active neonatal practice in the 1960s and 1970s when the
      majority of these trials were likely to have been done. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials in newborn infants with
      respiratory failure due to pulmonary disease evaluating the use of MV versus
      standard neonatal care without MV. DATA COLLECTION AND ANALYSIS: The standard
      methods of the Cochrane Collaboration and its Neonatal Review Group were used.
      Two authors independently assessed eligibility, methodological quality of each
      trial and extracted the data. Additional information was obtained from all trial
      authors on methodology or data. The data were analysed using relative risk and
      risk difference and their 95% confidence intervals. A fixed effect model was used
      for meta-analyses. MAIN RESULTS: The five trials reported on a total of 359
      infants with RDS. In one study there is a higher neonatal mortality in the
      mechanical ventilation group [7/10 vs 1/10; RR 7.00 (1.04, 46.95)]. Overall any
      reported mortality is less frequent in the mechanical ventilation group with the
      upper 95% confidence limit on 1.00 [summary RR 0.86 (0.74, 1.00), RD -0.10 (
      0.20, -0.01), NNT 10 (5, 100)]. In infants with a birth weight of 1 - 2 kg, no
      significant difference in mortality is found [summary RR for two trials 0.86
      (0.70, 1.07)]. In infants with a birth weight of more than 2 kg, one study
      reports a significant reduction in mortality in the MV group compared with
      control [RR 0.67 (0.51, 0.86)]; overall for this birth weight group there is a
      significant reduction in mortality with MV in the two trials [summary RR 0.67
      (0.52, 0.87), RD -0.27 (-0.45, -0.10), NNT 4 (2, 10)]. Any IVH at autopsy is not
      significantly different between the groups in any study or overall in four
      studies reporting on 202 infants who had an autopsy. Pneumothorax was reported in
      two studies of 275 infants and there is a non-significant trend towards an
      increase in the mechanical ventilation group [summary RR 2.75 (0.72, 10.45)].
      REVIEWER'S CONCLUSIONS: When MV was introduced in the 1960s to treat infants with
      severe respiratory failure due to pulmonary disease, trials showed an overall
      reduction in mortality which was most marked in infants born with a birthweight
      of more than 2 kg. This review does not provide information to evaluate the
      relative benefits or harms of MV in the setting of modern perinatal care. In
      settings without modern neonatal care, the introduction of MV should ideally be
      evaluated in randomised controlled trials for its relative benefits, harms and
      costs.

PMID- 12519576
TI  - Heparin for prolonging peripheral intravenous catheter use in neonates.
AB  - BACKGROUND: Peripheral intravenous (PIV) catheters are widely used in modern
      medical practice. However, mechanical or infectious complications often
      necessitate their removal and/or replacement. Heparin has been shown to be
      effective in prolonging the patency of peripheral arterial catheters and central
      venous catheters, but may result in life threatening complications, especially in
      preterm neonates. OBJECTIVES: The primary objective was to determine the
      effectiveness of heparin versus placebo or no treatment on duration of PIV
      catheter patency, defined as number of hours of catheter use. The secondary
      objectives were to assess the effects of heparin on catheter blockage, phlebitis
      or thrombophlebitis, catheter related sepsis, and complications including
      abnormality of coagulation profile, allergic reactions to heparin, heparin
      induced thrombocytopenia, intraventricular/intracranial hemorrhage and mortality.
      SEARCH STRATEGY: A literature search was performed using the following databases:
      MEDLINE (1966-December 2001), EMBASE (1980-December 2001), CINAHL (1982-December
      2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001),
      and abstracts from the annual meetings of the Society for Pediatric Research,
      American Pediatric Society and Pediatric Academic Societies published in
      Pediatric Research (1991-2001). No language restrictions were applied. SELECTION
      CRITERIA: Randomized or quasi-randomized trials of heparin administered as flush
      or infusion versus placebo or no treatment were included. Studies which included
      a neonatal population and reported on at least one of the outcomes were included.
      DATA COLLECTION AND ANALYSIS: The methodological quality of the studies was
      assessed using criteria for blinding of randomization, blinding of intervention,
      completeness of follow-up and blinding of outcome assessment. Data on relevant
      outcomes were extracted and the effect size was estimated by calculating WMD
      (weighted mean difference, 95%CI), RR (relative risk, 95% CI) and RD (risk
      difference, 95% CI). MAIN RESULTS: Eight eligible studies were identified.
      Heparin was administered either as a flush solution or as an additive to the
      total parenteral nutrition solution. Five studies reported data on the duration
      of use of the first catheter. Two of these studies found no statistically
      significant effect of heparin; two studies showed a statistically significant
      increase and one study showed a statistically significant decrease in the
      duration of PIV catheter use in the heparin group. The results were not combined
      for meta-analysis due to significant heterogeneity of the treatment effect
      (p<0.01). In addition, there were marked differences between the studies in terms
      of the methodological quality, the dose, the timing, the route of administration
      of heparin and the outcomes reported. From a limited number of studies, there
      were no significant differences between the heparin and the placebo/no treatment
      groups in the risks of infiltration, phlebitis and intracranial hemorrhage.
      REVIEWER'S CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: The effect of heparin on the
      duration of peripheral intravenous catheter use varied across the studies.
      Because of clinical heterogeneity and heterogeneity in treatment effect,
      recommendations for heparin use in neonates with PIV catheters cannot be made.
      IMPLICATIONS FOR RESEARCH: There are insufficient data concerning the effect of
      heparin for prolonging PIV catheter use in neonates. Further research on the
      effectiveness, the optimal dose, and the safety of heparin is required.

PMID- 12519577
TI  - Chelation therapy for atherosclerotic cardiovascular disease.
AB  - BACKGROUND: Chelation therapy is being promoted and practiced all over the world
      as a form of alternative medicine in the treatment of atherosclerotic
      cardiovascular disease. It has been recommended as a safe, relatively inexpensive
      and non-surgical method of restoring blood flow in atherosclerotic vessels. At
      present the benefit of chelation therapy remains controversial at best.
      OBJECTIVES: The objective of this review is to assess the effects of ethylene
      diamine tetraacetic acid (EDTA) chelation therapy on clinical outcomes among
      patients with atherosclerotic cardiovascular disease. SEARCH STRATEGY: The
      reviewers searched the Cochrane Peripheral Vascular Diseases Group Trials
      Register, (last searched July 2002), the Cochrane Controlled Trials Register,
      (Cochrane Library Issue 2, 2002), MEDLINE and EMBASE for published articles and
      other relevant articles. Studies were also requested through correspondence with
      known Filipino practitioners of the procedure. SELECTION CRITERIA: Studies were
      included if they were randomized controlled trials of EDTA chelation therapy
      versus placebo or no treatment in patients with atherosclerotic cardiovascular
      disease. Main outcome measures considered included either total or cause-specific
      mortality, non-fatal cardiovascular events, direct or indirect measurement of
      disease severity, subjective measures of improvement or adverse events. DATA
      COLLECTION AND ANALYSIS: Two reviewers (MVV, FT) extracted data and assessed
      trial quality independently. Unresolved issues were considered by a third
      reviewer (ALD). Discrepancies were discussed until a consensus was reached.
      Authors were contacted for additional information. MAIN RESULTS: A total of five
      studies was included in the review. Mortality, non-fatal events, and
      cerebrovascular events were not reported in any of the studies. Four of the
      studies, with a total recruitment rate of 250 participants, showed no significant
      difference in the following outcomes: direct or indirect measurement of disease
      severity and subjective measures of improvement. One of the studies, which
      included only 10 patients, was interrupted prematurely, because of an apparent
      treatment effect. However, relevant data were not available in the report and
      have been requested from the authors. REVIEWER'S CONCLUSIONS: At present, there
      is insufficient evidence to decide on the effectiveness or ineffectiveness of
      chelation therapy in improving clinical outcomes of patients with atherosclerotic
      cardiovascular disease. This decision must be preceded by conducting randomized
      controlled trials that would include endpoints that show the effects of chelation
      therapy on longevity and quality of life among patients with atherosclerotic
      cardiovascular disease.

PMID- 12519578
TI  - Cyclophosphamide for multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis is a presumed cell-mediated autoimmune disease of
      the central nervous system. Cyclophosphamide (CFX) is a cytotoxic and
      immunosuppressive agent, used in systemic autoimmune diseases. Controversial
      results have been reported on its efficacy in MS. We conducted a systematic
      review of all relevant trials, evaluating the CFX efficacy in patients with
      progressive MS. OBJECTIVES: The main objectives were to determine whether CFX
      slows the disease progression. SEARCH STRATEGY: Electronic databases (including
      MEDLINE, EMBASE, Cochrane Controlled Trials Register) were systematically
      searched. References list of retrieved studies and conference abstracts on the
      main meetings on Multiple Sclerosis were handsearched. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) evaluating the clinical effect of CFX
      treatment in patients affected by clinically definite progressive MS. CFX had to
      be administered alone or in combination with ACTH or steroids. The comparison
      group had to be placebo or no treatment or the same co intervention (ACTH or
      steroids) The main outcome criteria were : progression of disability (defined as
      an increase of 0.5 point in Kurtzke Extended Disability Status Scale (EDSS) for
      patients with baseline EDSS > or = 6 and 1 for EDSS < or = 5.5), differences of
      disability between treatment-control groups and the number of patients with side
      effects. DATA COLLECTION AND ANALYSIS: The identified references were reviewed by
      two reviewers who independently decided the eligibility of the study, extracted
      and summarized data and assessed the trial's quality. The statistical analysis
      was performed using the Cochrane RevMan software and analyzed using Cochrane
      MetaView. MAIN RESULTS: Of the 326 identified references, 80 were selected for
      full review, only four RCTs were selected for the final analysis. Intensive
      immunosuppression with CFX (alone or associated with ACTH or prednisone) in
      patients with progressive MS compared to placebo or no-treatment (152
      participants) did not prevent the long -term (12-18-24 months) risk to evolution
      to a next step of EDSS. However, the mean change in disability (final disability
      subtracted from the baseline) significantly favoured the treated group at 12
      (effect size - 0.21; C. I. - 0.24, - 0.17) and 18 months (- 0.19; C. I. - 0.24, -
      0.14). We were not able to verify the efficacy of other schedules. Five patients
      died; sepsis and amenorrhea frequently occurred in treated patients (descriptive
      analysis). REVIEWER'S CONCLUSIONS: Only limited objectives were reached. This
      review shows a role of CFX in the treatment of progressive MS, but less toxic
      schedules must be considered, before its use in the clinical practice.

PMID- 12519579
TI  - Interventions for relieving the pain and discomfort of screening mammography.
AB  - BACKGROUND: Pain of mammography is recognised as a significant deterrent to
      breast screening and therefore may effect the success or failure of any screening
      programme. OBJECTIVES: To review research of interventions related to any aspect
      of breast screening to reduce or relieve the pain and discomfort of screening
      mammography. SEARCH STRATEGY: The Cochrane Breast Cancer Group conducted a search
      of their specialised register in the Cochrane Library. In addition a wide variety
      of databases and websites were searched using keywords 'mammography' and 'pain',
      along with handsearching selected journals. Information was requested from a wide
      range of interested people and organisations. SELECTION CRITERIA: Randomised
      controlled trials and non-randomised trials with a comparison group were
      considered. Studies had to include assessment of both pain and quality of
      mammograms. DATA COLLECTION AND ANALYSIS: Identified studies were independently
      reviewed by two reviewers to determine if they met the inclusion criteria.
      Additional information was sought from investigators as necessary. Each study was
      reviewed for quality, including concealment of the allocation sequence,
      generation of the allocation sequence, comparability between groups at the
      baseline, inclusion of all randomised participants in the analysis and blinding
      after allocation. MAIN RESULTS: Three RCTs were identified for inclusion. A well
      designed study found that patient controlled breast compression gave a
      significant reduction in discomfort. However, the quality of mammograms was only
      maintained if the technologist controlled the first compression. Another study
      involved the technologist reducing compression force for one view. This study was
      poorly designed and showed no significant differences. The result was the same in
      a well designed study of the use of acetoaminophen as a premedication. The
      differences in interventions, and the inconsistency in measures and validation of
      pain scales and assessment of quality of mammograms, mean that the results of the
      studies cannot be combined. REVIEWER'S CONCLUSIONS: The only intervention
      suggesting significant reduction in the pain and discomfort was of patient
      controlled compression. Further research is required to determine if these
      findings can be replicated. Reducing technologist applied compression force did
      not result in significant reduction in pain suggesting that more than actual
      compression force is involved in pain and discomfort. However, the poor design of
      this study could have influenced the results. Premedication with acetoaminophen
      has no effect on the pain of mammography. More research into interventions to
      reduce the pain of mammography is needed if this is to continue as the preferred
      screening method in the detection of breast cancer.

PMID- 12519580
TI  - Devices and pressure sources for administration of nasal continuous positive
      airway pressure (NCPAP) in preterm neonates.
AB  - BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is used to support
      preterm infants recently extubated, those experiencing significant apnoea of
      prematurity and those with respiratory distress soon after birth as an
      alternative to intubation and ventilation. This review will focus exclusively on
      identifying the most effective pressure source and interface for NCPAP delivery
      in preterm infants. OBJECTIVES: In preterm infants extubated to NCPAP following
      intermittent positive pressure ventilation (IPPV) for respiratory distress
      syndrome (RDS) or in those treated with NCPAP soon after birth, which technique
      of pressure generation and which type of nasal interface for NCPAP delivery most
      effectively reduces the need for additional respiratory support? SEARCH STRATEGY:
      The strategy included searches of MEDLINE (1966-2002), the Cochrane Controlled
      Trials Register (The Cochrane Library, Issue 1, 2002), CINAHL, abstracts from
      conference proceedings, cross-referencing of previous reviews and the use of
      expert informants. SELECTION CRITERIA: Randomised or quasi-randomised trials
      comparing different techniques of NCPAP pressure generation and/or nasal
      interfaces in preterm infants extubated to NCPAP following IPPV for RDS or
      treated with NCPAP soon after birth. DATA COLLECTION AND ANALYSIS: Data was
      extracted and analysed by the first three authors. Dichotomous results were
      analysed using the relative risk (RR), risk difference (RD) and number needed to
      treat (NNT). MAIN RESULTS: 1. Preterm infants being extubated to NCPAP following
      a period of IPPV for RDS: Meta-analysis of the results from Davis 2001 and
      Roukema 1999a demonstrated that short binasal prongs are more effective at
      preventing re-intubation than single nasal or nasopharyngeal prongs [typical RR
      0.59 (CI: 0.41, 0.85), typical RD -0.21 (CI: -0.35, -0.07), NNT 5 (CI: 3, 14)].
      In the single study comparing short binasal prong devices (Sun 1999) the re
      intubation rate was significantly lower with the Infant Flow Driver than with the
      Medicorp prong [RR 0.33 (CI: 0.17, 0.67), RD -0.32 (CI: -0.49, -0.15), NNT 3 (CI:
      2, 7)]. 2. Preterm infants primarily treated with NCPAP soon after birth: The one
      trial identified, Mazzella 2001, found a significantly lower oxygen requirement
      and respiratory rate in those randomised to short binasal prongs when compared
      with CPAP delivered via nasopharyngeal prong. The requirement for intubation
      beyond 48 hours from randomisation was not assessed. No studies comparing
      different techniques of pressure generation were identified. REVIEWER'S
      CONCLUSIONS: Short binasal prong devices are more effective than single prongs in
      reducing the rate of re-intubation. Although the Infant Flow Driver appears more
      effective than Medicorp prongs the most effective short binasal prong device
      remains to be determined. The improvement in respiratory parameters with short
      binasal prongs suggests they are more effective than nasopharyngeal CPAP in the
      treatment of early RDS. Further studies incorporating longer-term outcomes are
      required. Studies are also needed to determine the optimal pressure source for
      the delivery of NCPAP.

PMID- 12519581
TI  - Acyclovir for treating varicella in otherwise healthy children and adolescents.
AB  - BACKGROUND: Acyclovir has the potential to shorten the course of illness which
      may result in reduced costs and morbidity. OBJECTIVES: 1) To examine the evidence
      evaluating the efficacy of acyclovir in alleviating symptoms and shortening the
      duration of illness. 2) To examine complications of chickenpox and adverse
      effects associated with acyclovir as reported in the relevant trials. SEARCH
      STRATEGY: We searched the Cochrane Controlled Trials Register (2002, Issue 2),
      MEDLINE (January 1966 to October 2001), EMBASE (1988 to September 2001). The
      reference lists of all relevant articles were reviewed. The primary author of
      relevant studies and the pharmaceutical company that manufactures acyclovir were
      contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated
      otherwise healthy children 0-18 years of age with chickenpox. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently reviewed the studies for eligibility. Two
      reviewers independently assessed methodological quality of the relevant studies
      using the Jadad scale and allocation concealment. Differences were resolved by
      consensus. Data were extracted by one reviewer using a structured form and
      checked by a second. Continuous data were converted to the weighted mean
      difference (WMD). Weighted mean differences were not combined into an overall
      estimate due to the varied age groups between studies. There were too few studies
      to consider statistical heterogeneity between studies (i.e., differences in
      reported effects), to perform subgroup or sensitivity analyses, or to assess for
      publication bias. MAIN RESULTS: Three studies were included. Study quality was
      three (n=2) and four (n=1) on the Jadad scale. Acyclovir was associated with a
      reduction in the number of days with fever, from -1.0 (95% CI -1.5,-0.5) to -1.3
      (95% CI -2.0,-0.6). Results were inconsistent with respect to the number of days
      to no new lesions, the maximum number of lesions and the number of days to the
      relief of itching. There were no clinically important differences between
      acyclovir and placebo with respect to complications associated with chickenpox or
      adverse effects associated with the drug. REVIEWER'S CONCLUSIONS: Acyclovir
      appears to be effective in reducing the number of days with fever among otherwise
      healthy children with chickenpox. The results were inconsistent with respect to
      the number of days to no new lesions, relief of itchiness and maximum number of
      lesions. The clinical importance of acyclovir treatment in otherwise healthy
      children remains controversial.

PMID- 12519582
TI  - Cardioselective beta-blockers for reversible airway disease.
AB  - BACKGROUND: Beta-blocker therapy has mortality benefit in patients with
      hypertension, heart failure and coronary artery disease, as well as during the
      perioperative period. These drugs have traditionally been considered
      contraindicated in patients with reversible airway disease. OBJECTIVES: To assess
      the effect of cardioselective beta-blockers in patients with asthma or COPD.
      SEARCH STRATEGY: A search of EMBASE, MEDLINE and CINAHL was performed up to May
      2002 using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*,
      wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic
      antagonist*, sympatholytic* or adrenergic receptor block*. SELECTION CRITERIA:
      Randomized, blinded, placebo-controlled trials of single dose or continued
      treatment of the effects of cardioselective beta-blockers in patients with
      reversible airway disease. DATA COLLECTION AND ANALYSIS: Two independent
      reviewers extracted data from the selected articles, reconciling differences by
      consensus. Beta1-blockers were divided into those with or without intrinsic
      sympathomimetic activity (ISA). Interventions were: administration of single or
      continued beta1-blocker, and response to beta2-agonist given after the study
      drug. MAIN RESULTS: Nineteen studies on single-dose treatment and 10 studies on
      continued treatment met the inclusion criteria. Single dose cardioselective beta
      blocker produced a 7.46% (95% CI 5.59, 9.32) reduction in FEV1, but with a 4.63%
      (95% CI 2.47, 6.78) increase in FEV1 with beta2-agonist, compared to placebo.
      Treatment lasting 3 - 28 days produced no change in FEV1 (-0.42%; 95% CI -3.74,
      2.91), symptoms or inhaler use, whilst maintaining a 8.74% (95% CI 1.96, 15.52)
      response to beta2-agonist. There was no significant change in FEV1 treatment
      effect for those patients with COPD: single doses -5.28% (95% CI -10.03, -0.54%),
      continued treatment 1.07% (CI -3.3, 5.44. With continued treatment there was no
      significant difference in FEV1 response for beta1-blockers without ISA compared
      to those with IS: -3.22% (96%CI -7.79, 1.36) compared to 2.72% (95% CI -2.12,
      7.59). Those without ISA produced a 12.0% increase in FEV1 after beta2-agonist
      administration compared to placebo (95%CI 4.12,19.87) while beta1-blockers with
      ISA produced no change compared to placebo (-0.60% [95%CI -13.93, 12.73). These
      results were obtained in a small number od studies of few patients. The
      difference was not significant. REVIEWER'S CONCLUSIONS: Cardioselective beta
      blockers given in mild - moderate reversible airway disease or COPD, do not
      produce adverse respiratory effects in the short term. Given their demonstrated
      benefit in conditions such as heart failure, cardiac arrhythmias and
      hypertension, these agents should not be withheld from such patients, but long
      term safety (especially their impact during an acute exacerbation) still needs to
      be established.

PMID- 12519583
TI  - Techniques for the interruption of tubal patency for female sterilisation.
AB  - BACKGROUND: Female sterilization is the most popular contraceptive method
      worldwide. Several techniques are described in the literature, however only few
      of them are commonly used and properly evaluated. OBJECTIVES: To compare the
      different tubal occlusion techniques in terms of major and minor morbidity,
      failure rates (pregnancies), technical failures and difficulties and women's and
      surgeons' views. SEARCH STRATEGY: The Cochrane Controlled Trials Register has
      been searched. A search of the reference lists of identified trials was
      performed. An additional MEDLINE search was done using an Internet search service
      Pub Med. SELECTION CRITERIA: All randomized controlled trials comparing different
      techniques for tubal sterilization, regardless of the way of entry in the
      abdominal cavity or the method of anesthesia. DATA COLLECTION AND ANALYSIS:
      Trials under consideration were evaluated for methodological quality and
      appropriateness for inclusion. Nine relevant studies were included and the
      results were stratified in five groups: tubal ring versus clip, modified Pomeroy
      versus electrocoagulation, tubal ring versus electrocoagulation, modified Pomeroy
      versus Filshie clip and Hulka versus Filshie clip. Results are reported as odds
      ratio for dichotomous outcomes and weighted mean differences for continuous
      outcomes. MAIN RESULTS: Tubal ring versus clip: Minor morbidity was higher in the
      ring group (Peto OR 2.15; 95% CI 1.22, 3.78). Technical difficulties were found
      less frequent in the clip group ( Peto OR 3.87; 95% CI 1.90, 7.89). There was no
      difference in failure rates between the two groups (Peto OR 0.70; 95% CI 0.28,
      1.76). Pomeroy versus electrocoagulation: Women undergoing modified Pomeroy
      technique had higher major morbidity than with electrocoagulation technique (Peto
      OR 2.87; 95% CI 1.13, 7.25). Postoperative pain was more frequent in the Pomeroy
      group (Peto OR 3.85; 95% CI 2.91, 5.10). Tubal ring versus electrocoagulation:
      Post operative pain was more frequently reported in the tubal ring group. No
      pregnancies were reported. Pomeroy versus Filshie clip: In the trial comparing
      the two interventions only one pregnancy was reported in the Pomeroy group after
      follow-up for 24 months. No differences were found when comparing Hulka versus
      Filshie clip in the only study that compared these two devices (Toplis 1988).
      REVIEWER'S CONCLUSIONS: Electrocoagulation was associated with less morbidity
      when compared with tubal ring and other methods. However the risk of burns to the
      small bowel might be a serious criticism of the approach. The small sample size
      and the relative short period of follow-up in these studies limited the power to
      show clinical or statistical differences for rare outcomes such as failure rates.
      Aspects such as training, costs and maintenance of the equipment may be important
      factors in deciding which method to choose.

PMID- 12519584
TI  - Medical versus surgical methods for first trimester termination of pregnancy.
AB  - BACKGROUND: Induced abortions are very commonly practiced interventions
      worldwide. A variety of medical abortion methods have been introduced during the
      last decade in addition to existing surgical methods. In this review we
      systematically searched for and combined all evidence from randomised controlled
      trials comparing surgical with medical abortion. OBJECTIVES: To evaluate medical
      methods in comparison to surgical methods for first-trimester abortion with
      respect to efficacy, side effects and acceptability. SEARCH STRATEGY: The
      Cochrane Controlled Trials Register, MEDLINE (with the Cochrane 3-stage search
      strategy)(1966-2000) and Popline (1970-2000) were systematically searched. There
      were no language preferences in searching. Reference lists of retrieved papers
      were searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Randomised
      trials of any surgical abortion method compared with any medical abortion method
      in the first trimester. DATA COLLECTION AND ANALYSIS: Trial quality was assessed
      and data extraction was made independently by two reviewers. MAIN RESULTS: Five
      studies mostly with small sample sizes, comparing 4 different interventions
      (prostaglandins alone, mifepristone alone, and mifepristone/misoprostol and
      methotrexate/misoprostol versus vacuum aspiration) were included. Results are
      sometimes based on one trial only. Prostaglandins vs vacuum aspiration: the rate
      of abortions not completed with the intended method was statistically significant
      higher in the prostaglandin group (2.7, 95% CI 1.1 to 6.8) compared to surgery.
      There are no data on the most commonly medical (mifepristone/misoprostol) and
      surgical abortion available to be included in the review. Duration of bleeding
      was longer in the medical abortion groups compared to vacuum aspiration. There
      was only one major complication (uterine perforation) in one trial in the
      surgical group. There was no difference between the groups for ongoing
      pregnancies at the time of follow-up or pelvic infections. No data on
      acceptability, side effects or women's satisfaction with the procedure were
      available for inclusion in the review. REVIEWER'S CONCLUSIONS: The results are
      derived from small trials. Prostaglandins used alone seems to be less effective
      and more painful compared to surgical first-trimester abortion. However, there is
      inadequate evidence to comment on the acceptability and side effects of medical
      compared to surgical first-trimester abortions. There is a need for trials to
      address the efficacy of currently used methods and women's preferences more
      reliably.

PMID- 12519585
TI  - Community animal health services for improving household wealth and health status
      of low income farmers.
AB  - BACKGROUND: Community animal health services in low income countries aim to
      improve the health of animals. They are thought to directly improve the wealth
      and health or livelihood of their owners. These services have been promoted since
      the 1970s by aid organizations. OBJECTIVES: To summarize reliable research of
      community animal health services on indicators for household wealth and health.
      SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized
      trials register (up to May 2002); the AGRIS database (January 1975 to April
      2002); STN SIGLE database (January 1976 to 2002); CAB database (January 1973 to
      January 2002); AGRICultural OnLine Access (US National Agricultural Library;
      accessed 30 April 2002); MEDLINE (PubMed; 1966 to April 2002); the Science
      Citation Index (2000 to April 2002); and checked the reference lists of articles.
      We searched 24 relevant web sites and contacted 22 organizations between July and
      September 2000. SELECTION CRITERIA: Individual, cluster and quasi-randomized
      controlled trials, and controlled before and after studies: comparing community
      animal health services with no community animal health services, or with an
      alternative animal health service. DATA COLLECTION AND ANALYSIS: We independently
      assessed studies for inclusion in the review. We contacted study authors for
      additional information. MAIN RESULTS: No studies met the inclusion criteria.
      Subsidiary analysis of excluded studies indicate a need for methodological rigor
      in evaluating programmes. REVIEWER'S CONCLUSIONS: No studies met the inclusion
      criteria. Reports that draw on observational data show insufficient rigor to
      conclude benefit. Given the amount of money and time invested in this area, these
      observations need to be confirmed by well-designed trials using pragmatic
      outcomes.

PMID- 12519586
TI  - Ginkgo biloba for cognitive impairment and dementia.
AB  - BACKGROUND: Extracts of the leaves of the maidenhair tree, Ginkgo biloba, have
      long been used in China as a traditional medicine for various disorders of
      health. A standardized extract is widely prescribed in Germany and France for the
      treatment of a range of conditions including memory and concentration problems,
      confusion, depression, anxiety, dizziness, tinnitus and headache. The mechanisms
      of action are thought to reflect the action of several components of the extract
      and include increasing blood supply by dilating blood vessels, reducing blood
      viscosity, modification of neurotransmitter systems, and reducing the density of
      oxygen free radicals. OBJECTIVES: The aim of the review is to assess the efficacy
      and safety of Ginkgo biloba for the treatment of patients with dementia or
      cognitive decline. SEARCH STRATEGY: Trials were identified on 26 June 2002
      through a search of the CDCIG Specialized Register which contains records from
      all main medical databases (MEDLINE, EMBASE, CINAHL, PsycINFO, SIGLE,LILACS),
      from ongoing trials databases such as Clinicaltrials.gov and Current Controlled
      Trials and many other sources. The search terms used were ginkgo*, tanakan, EGB
      761, EGB761 and "EGB 761". SELECTION CRITERIA: All relevant, unconfounded,
      randomized, double-blind controlled studies, in which extracts of Ginkgo biloba
      at any strength and over any period were compared with placebo for their effects
      on people with acquired cognitive impairment, including dementia, of any degree
      of severity. DATA COLLECTION AND ANALYSIS: Data for the meta-analyses are based
      on reported summary statistics for each study. For the intention-to-treat
      analyses we sought data for each outcome measure on every patient randomized,
      irrespective of compliance. For the analyses of completers we sought data on
      every patient who completed the study on treatment. For continuous or ordinal
      variables, such as psychometric test scores, clinical global impression scales,
      and quality of life scales, there are two possible approaches. If ordinal scale
      data appear to be approximately normally distributed, or if the analyses reported
      by the investigators suggest that parametric methods and a normal approximation
      are appropriate, then the outcome measures will be treated as continuous
      variables. The second approach, which may not exclude the first, is to
      concatenate the data into two categories which best represent the contrasting
      states of interest, and to treat the outcome measure as binary. For binary
      outcomes, the endpoint itself is of interest and the Peto method of the typical
      odds ratio is used. MAIN RESULTS: Overall, there are no significant differences
      between Ginkgo and placebo in the proportion of participants experiencing adverse
      events. Most studies report the analyses of data from participants who completed
      the treatment, there are few attempts at ITT analyses. Therefore we report
      completers analyses only. The CGI scale, measuring clinical global improvement as
      assessed by the physician, was dichotomized between participants who showed
      improvement and those who were unchanged or worse. There are benefits associated
      with Ginkgo (dose less than 200mg/day) compared with placebo at less than 12
      weeks (54/63 showed improvement compared with 20/63, OR 15.32, 95% CI 5.90 to
      39.80, P=<.0001), and Ginkgo (dose greater than 200mg/day) at 24 weeks (57/79
      compared with 42/77, OR 2.16, 95% CI 1.11 to 4.20, P=.02). Cognition shows
      benefit for Ginkgo (dose less than 200mg/day) compared with placebo at 12 weeks
      (SMD -0.57, 95% CI -1.09, -0.05, P=0.03, random effects model), Ginkgo (greater
      than 200 mg/day) at 12 weeks (SMD -0.56, 95% CI -1.12 to -0.0, P=0.05), at 12
      weeks (Ginkgo any dose) (SMD -0.71, 95% CI -1.23 to -0.19 P=0.008, random effects
      model) at 24 weeks (Ginkgo any dose) (SMD -0.17, 95% CI -0.32 to -0.02 P=0.03)
      and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41, 95% CI -0.71 to -0.11,
      P=<.01). Activities of Daily Living (ADL) shows benefit for Ginkgo (dose less
      than 200mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, 
      0.41, P=0mg/day) compared with placebo at 12 weeks (SMD -1.10, 95% CI -1.79, 
      0.41, P=<.01), Ginkgo (dose less than 200 mg/day ) at 24 weeks (SMD -0.25, 95% CI
      -0.49 to -0.00, P=.05), and at 52 weeks (Ginkgo less than 200 mg/day) (SMD -0.41,
      95% CI -0.71 to -0.11, P=<.01). Measures of mood and emotional function show
      benefit for Ginkgo (dose less than 200 mg/day) compared with placebo at less than
      12 weeks (SMD -0.51, 95% CI -0.99 to -0.03, P=.04) and Ginkgo (dose less than
      200mg/day) at 12 weeks (SMD -1.94, 95% CIs -2.73, -1.15 P=<.0001). There are no
      significant differences between Ginkgo and placebo in the proportion of
      participants experiencing adverse events. There are no data available on Quality
      of Life, measures of depression or dependency. REVIEWER'S CONCLUSIONS: Ginkgo
      biloba appears to be safe in use with no excess side effects compared with
      placebo. Many of the early trials used unsatisfactory methods, were small, and we
      cannot exclude publication bias. Overall there is promising evidence of
      improvement in cognition and function associated with Ginkgo. However, the three
      more modern trials show inconsistent results. Our view is that there is need for
      a large trial using modern methodology and permitting an intention-to-treat
      analysis to provide robust estimates of the size and mechanism of any treatment
      effects.

PMID- 12519587
TI  - Snoezelen for dementia.
AB  - BACKGROUND: Snoezelen, multi-sensory stimulation, provides sensory stimuli to
      stimulate the primary senses of sight, hearing, touch, taste and smell, through
      the use of lighting effects, tactile surfaces, meditative music and the odour of
      relaxing essential oils (Pinkney 1997). The clinical application of snoezelen has
      been extended from the field of learning disability to dementia care over the
      past decade. The rationale for its use lies in providing a sensory environment
      that places fewer demands on intellectual abilities but capitalizes on the
      residual sensorimotor abilities of people with dementia (e.g. Buettner 1999, Hope
      1998). Practitioners are keen to use snoezelen in dementia care, and some
      encouraging results have been documented in the area of promoting adaptive
      behaviours (e.g. Baker, Long 1992, Spaull 1998). However, the clinical
      application of snoezelen often varies in form, nature, principles and procedures.
      Such variations not only make examination of the therapeutic values of Snoezelen
      difficult, but also impede the clinical development of snoezelen in dementia
      care. A systematic review of evidence for the efficacy of snoezelen in the care
      of people with dementia is therefore needed to inform future clinical
      applications and research directions. OBJECTIVES: This review aims to examine the
      clinical efficacy of snoezelen for older people with dementia. SEARCH STRATEGY:
      "Snoezelen", "multi-sensory", "dement*", "Alzheimer*", "randomized control/single
      control/double control" were used as keywords to search seven electronic
      databases (e.g. MEDLINE, PsyLIT). The list of trials was compared with those
      identified from a search of the Specialized Register of the Cochrane Dementia and
      Cognitive Improvement Group. SELECTION CRITERIA: All RCTs in which Snoezelen or
      multi-sensory programmes were used as an intervention for people with dementia
      were included in the review. Trial data included in the review were restricted to
      those involving people aged over 60 years suffering from any type of dementia,
      except one subject of Baker's study was aged below 60 years. DATA COLLECTION AND
      ANALYSIS: Only two RCTs fulfill the inclusion criteria for this systematic
      review. Two reviewers independently extracted the data from these two inclusion
      studies. Quantitative synthesis of the comparable data from the two trials was
      performed. MAIN RESULTS: Two trials were included. Both Baker (and Kragt examined
      the short-term values of snoezelen on the behaviours of people with dementia.
      Although the pooled results were insignificant, the trend was in the direction of
      favouring treatment (hence a negative value of the SMD). The standardized mean
      difference (SMD) was -1.22, with a 95% confidence interval (CI) (-4.08, 1.64).
      Kragt's result, weighted 47%, was significant in favour of treatment, with a SMD
      of -2.77 and a 95% CI (-4.24, -1.29). During the snoezelen session, Kragt's
      subjects presented significantly fewer apathetic behaviours (t=-8.22, p<0.01),
      fewer restless behaviours (t=-3.00, p=0.01), fewer repetitive behaviours (t=
      .822, p<0.01), and fewer disturbances (t=-4.91, p<0.01). Baker's result was
      slightly not in favour of the treatment, with a SMD of 0.16 and a 95% CI (-0.41,
      0.73). The control subjects touched objects/equipment more appropriately within
      the activity sessions than the subjects who participated in snoezelen sessions
      (F(1,47)=5.96, p=.001). Kragt did not examine the carryover and long-term effects
      of snoezelen, so only Baker's results were analysed. Baker used the Behavioural
      and Mood Disturbance scale (BMD), the REHAB, the CAPE and MMSE to assess patients
      mood, behaviour and cognition after (but not immediately after) four treatment
      sessions and eight treatment sessions. Some assessments were carried at home,
      some at day hospital. There were many subscores and mostly there were no
      differences between treatment and control. The following significant differences
      were found with benefit in favour of snoezelen compared with control after four
      sessions: apathy ezelen compared with control after four sessions: apathy score
      of the BRS (CAPE) (MD -3.00, 95%CIs -5.87 to -0.13, P=0.04), after eight
      sessions: mood score of the BRS (CAPE) (MD -2.60, 95%CIs -4.92 to -0.28, P=0.03),
      total score of the BRS (CAPE) (MD -6.92, 95%CIs -13.13 to -0.7, P=0.03), speech
      skills of the REHAB (MD 1.46, 95%CIs 0.01 to 2.82, P=0.03), psychomotor subscore
      of the cognitive assessment scale of CAPE (MD -3.12, 95%CIs -5.31 to -0.93,
      P<0.01). REVIEWER'S CONCLUSIONS: Two trials were reviewed. Although both studies
      examined the short-term values of snoezelen on people with dementia, it is not
      feasible to draw a firm conclusion at this stage, for two main reasons. Firstly,
      very limited data were available for analysis, thus limiting data inference and
      generalization. Secondly, different methodology and control conditions were
      adopted in the two trials. Such variations not only require a careful
      interpretation of results but also make the comparison of results across studies
      less valid. Hence, there is an urgent need for more systematic and scientific
      research studies to examine the clinical value of snoezelen for people with
      dementia. To our knowledge, there are four RCTs currently in progress. It is
      hoped that the data and results of these trials will enrich the systematic review
      of snoezelen for dementia in the next update.

PMID- 12519588
TI  - Granulopoiesis-stimulating factors in the prevention for adverse effects in the
      therapeutic treatment of malignant lymphoma.
AB  - BACKGROUND: Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used
      to prevent febrile neutropenia and infections in the treatment of patients with
      malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity,
      tumour response and overall survival in this patient population has not been
      answered yet. Since the results from single studies are inconclusive a systematic
      review was required. OBJECTIVES: To undertake a systematic review in patients
      with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to
      prevent neutropenia, febrile neutropenia, infection, improve quality of life,
      adherence to the treatment protocol, tumour response, freedom from treatment
      failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and
      GM-CSF. SEARCH STRATEGY: Medline, Embase, CancerLit, the Cochrane Library and
      smaller databases, Internet-databases of ongoing trials, conference proceedings
      of the American Society of Clinical Oncology and the American Society of
      Hematology were searched. We included full-text and abstract publications as well
      as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing
      prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients
      with malignant lymphoma undergoing chemotherapy were included in this review.
      Both study arms had to receive identical chemotherapy and supportive care. DATA
      COLLECTION AND ANALYSIS: Eligibility and quality assessment, data extraction and
      analysis were done in duplicate. All authors were contacted to obtain missing
      data. MAIN RESULTS: We included 11 eligible studies with 1434 randomised
      patients. Compared with no prophylaxis, G-/GM-CSF significantly reduced the
      relative risk for severe neutropenia (RR 0.64 [95% CI 0.55-0.75]), febrile
      neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64
      0.85]). There was no evidence for G-/GM-CSF to decrease the number of patients
      who required iv antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection
      related mortality (RR 2.07 [95% CI 0.81-5.34]), or to improve complete tumour
      response (RR 1.06 [95% CI 0.96-1.16]), FFTF (HR 1.22 [95% CI 0.83-1.80]) and OS
      (HR 0.98 [95% CI 0.81-1.18]). None of the studies evaluated quality of life
      parameters. REVIEWER'S CONCLUSIONS: G-CSF and GM-CSF, when given prophylactically
      in patients with malignant lymphoma undergoing conventional chemotherapy, reduce
      the risk of neutropenia, febrile neutropenia and infection. However, based on the
      currently available randomised trials in this clinical setting, there is no
      evidence for G-/GM-CSF to provide a significant advantage in terms of complete
      tumour response, FFTF and OS.

PMID- 12519589
TI  - Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic
      dystrophy.
AB  - BACKGROUND: Excessive daytime sleepiness is a common symptom of myotonic
      dystrophy. Psychostimulants are drugs increasingly used to treat hypersomnia in
      myotonic dystrophy. OBJECTIVES: To search systematically for, and combine all
      evidence from, randomised trials relating to the effects of psychostimulants in
      myotonic dystrophy patients with hypersomnia. SEARCH STRATEGY: We searched the
      Cochrane Neuromuscular Disease Trial Register (searched May 2001) for randomised
      trials concerning psychostimulants in myotonic dystrophy, we searched of the
      bibliographies of identified papers and we contacted the authors of the papers.
      SELECTION CRITERIA: We considered all randomised or quasi randomised trials that
      have evaluated any type of psychostimulants (versus a placebo or no treatment) in
      children or adults with proven myotonic dystrophy and hypersomnia. DATA
      COLLECTION AND ANALYSIS: Potentially relevant papers were scrutinised by two
      reviewers and the selection of eligible studies was agreed by them and a third
      reviewer. Data were extracted by one reviewer and checked by a second reviewer.
      MAIN RESULTS: Primary outcome We found no trial that assessed the effect of a
      psychostimulant on the results of the maintenance of wakefulness tests. Secondary
      outcomes Only one eligible trial was found. In this crossover double blind study
      of 10 patients with myotonic dystrophy, the efficacy of selegiline was evaluated
      against a placebo on the multiple sleep latency test. There was no difference
      between the selegiline and placebo periods in mean improvement in the multiple
      sleep latency test scale. REVIEWER'S CONCLUSIONS: There is no evidence to support
      the use of a psychostimulant to treat hypersomnia in myotonic dystrophy.
      Randomised trials are needed to evaluate the efficacy and safety of
      psychostimulants.

PMID- 12519590
TI  - Anticoagulants versus antiplatelet agents for acute ischaemic stroke.
AB  - BACKGROUND: Antiplatelet agents produce a small, but worthwhile benefit in long
      term functional outcome and survival, and have become standard treatment for
      acute ischaemic stroke. Anticoagulants are often used as an alternative
      treatment, despite evidence that they are ineffective in producing long-term
      benefits. We wanted to review trials which have directly compared anticoagulants
      and antiplatelet agents, to assess whether any anticoagulant regimen offers net
      advantages over antiplatelet agents, overall or in some particular category of
      patients (e.g. patients with atrial fibrillation). OBJECTIVES: a) To assess the
      effectiveness of anticoagulants compared with antiplatelet agents in acute
      ischaemic stroke b) To assess whether the addition of anticoagulants to
      antiplatelet agents offers any net advantage over antiplatelet agents alone.
      SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register, the
      Cochrane Controlled Trials Register (Central/CCTR), the trials register held by
      the Antithrombotic Therapy Trialists' Collaboration, MEDLINE (1966-2000), and
      EMBASE (1980-2000). All searches were performed during April and May 2001.
      SELECTION CRITERIA: Truly unconfounded, randomised-controlled trials comparing
      anticoagulants with antiplatelet agents, or anticoagulants and antiplatelet
      agents with antiplatelet agents alone, given within 14 days of onset of presumed
      or confirmed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Both reviewers
      independently selected trials for inclusion in the review, assessed trial quality
      and extracted data. MAIN RESULTS: A total of 16,558 patients from four trials
      contributed to the analyses. The methodological quality was high in all four
      trials. The anticoagulants tested were unfractionated heparin (UFH) and low
      molecular-weight heparin. Aspirin was used as control in all trials. Overall,
      there was no evidence that anticoagulants were superior to aspirin in reducing
      'death or dependency' at long-term follow-up (odds ratio [OR] 1.07, 95%
      confidence interval [95% CI] 0.98-1.15). Compared with aspirin, anticoagulants
      were associated with a small but significant increase in the number of deaths at
      the end of follow-up (OR 1.10, 95% CI 1.01-1.29), equivalent to 20 more deaths
      (95% CI 0-30) per 1000 patients treated; a significant increased risk of
      symptomatic intracranial haemorrhage (OR 2.35, 95% CI 1.49-3.46); and a non
      significant increased risk of 'any recurrent stroke' during treatment (OR 1.20,
      95% CI 0.99-1.46). These neutral or adverse effects outweighed a small, but
      significant effect on symptomatic deep vein thrombosis (OR 1.20, 95% CI 0.07
      0.58), equivalent to 10 fewer (95% CI 0-30) DVTs by 14 days per 1000 patients
      treated with anticoagulants instead of aspirin. Subgroup analysis could not
      identify any type, dose, or route of administration of anticoagulants associated
      with net benefit, or any benefit in patients with atrial fibrillation. Overall,
      the combination of UFH and aspirin did not appear to be associated with a net
      advantage over aspirin alone. A subgroup analysis showed that, compared with
      aspirin, the combination of low-dose UFH and aspirin was associated with a
      marginally significant reduced risk of 'any recurrent stroke' (OR 0.75, 95% CI
      0.56-1.03) and a marginally significant reduced risk of death at 14 days (OR
      0.84, 95% CI 0.69-1.01), and with no clear adverse effect on death at end of
      follow-up (OR 0.98, 95% CI 0.85-1.12). REVIEWER'S CONCLUSIONS: Anticoagulants
      offered no net advantages over antiplatelet agents in acute ischaemic stroke. The
      combination of low-dose UFH and aspirin appeared in a subgroup analysis to be
      associated with net benefits compared with aspirin alone, and this merits further
      research.

PMID- 12519591
TI  - Dapsone as an oral corticosteroid sparing agent for asthma.
AB  - BACKGROUND: Oral corticosteroids are used as a treatment for asthma, however they
      are often associated with serious side effects. Dapsone is a sulfone with anti
      inflammatory properties, therefore it may have a beneficial effect in the
      treatment of asthma and act as a corticosteroid-sparing agent. OBJECTIVES: The
      objective of this review is to assess the safety and efficacy of adding dapsone
      to oral corticosteroids in adults with stable asthma who are dependent on oral
      corticosteroids with the intention of eventually minimizing or eliminating the
      use of these steroids. SEARCH STRATEGY: The Cochrane Airways group trials
      register and reference lists of potential articles were searched. SELECTION
      CRITERIA: Randomised controlled trials investigating the addition of dapsone
      compared to placebo in stable corticosteroid dependent asthmatics. DATA
      COLLECTION AND ANALYSIS: No trials were found that met the selection criteria.
      MAIN RESULTS: No meta-analyses could be performed. REVIEWER'S CONCLUSIONS: No
      randomised controlled trials have been published, so there is no reliable
      evidence to show whether dapsone is beneficial or otherwise in the management of
      steroid-dependent asthmatic patients. There is a need for well designed
      randomised controlled trials to be performed. These must be carried out double
      blind, since oral corticosteroid reduction requires a judgement on the part of
      the physician, who may be open to bias if the treatment allocation is known.

PMID- 12519592
TI  - Autologous cartilage implantation for full thickness articular cartilage defects
      of the knee.
AB  - BACKGROUND: A variety of strategies have been employed for managing articular
      cartilage defects of the knee, including drilling and abrasion arthroplasty.
      These treatments are not always effective and when they are, the benefits may
      only be transitory. Unsuccessfully treated cartilage damage may progress to
      degenerative disease states and result in the need for a total knee replacement.
      In recent years the surgical implantation of healthy cartilage cells (autologous
      cartilage implantation [ACI] ) into damaged areas has been seen as an alternative
      option and is currently under investigation as a potential improvement over the
      current strategies for the management and treatment of articular cartilage
      defects. OBJECTIVES: To determine the effectiveness of ACI in patients with full
      thickness articular cartilage defects of the knee. SEARCH STRATEGY: We searched
      the Cochrane Musculoskeletal Injuries Group specialised register (May 2002),
      Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002),
      MEDLINE (1966 to June Week 4 2001), CINAHL (1982 to July Week 2 2001), EMBASE
      (1980 to 2001 Week 27), SPORTDiscus (1949 to June 2001), Current Contents (1993
      Week 26 to 2001 Week 30) and the National Research Register (Issue 2, May 2002).
      SELECTION CRITERIA: Randomised and quasi-randomised trials comparing ACI with any
      other type of treatment (including no treatment or placebo) for symptomatic
      cartilage defects of the medial or lateral femoral condyle, trochlea or patella.
      DATA COLLECTION AND ANALYSIS: Two independent reviewers applied the entry
      criteria to identified studies. MAIN RESULTS: No completed randomised controlled
      trials investigating this treatment were identified through the above searches.
      One possible trial has been placed in Studies Awaiting Assessment, awaiting
      translation of the full trial report. Ongoing trials currently underway will be
      incorporated in future updates of this review. REVIEWER'S CONCLUSIONS: No
      information is available from RCTs which can influence current practice.
      Therefore, since current evidence is subject to the inherent weaknesses of case
      series or reports, ACI must currently be considered as a technology under
      investigation whose effectiveness is yet to be determined in well designed and
      conducted clinical trials. The results of ongoing randomised clinical trials will
      help improve this situation.

PMID- 12519593
TI  - Benzodiazepines and related drugs for insomnia in palliative care.
AB  - BACKGROUND: Insomnia, a subjective complaint of poor sleep and associated
      impairment in daytime function, is a common problem. Currently, benzodiazepines
      are the most used pharmacological treatment for this complaint. They are
      considered helpful for occasional short-term use up to four weeks but longer term
      use is not advised due to potential problems regarding tolerance, dosing
      escalation, psychological addiction and physical dependence. There is no
      consensus on their utility in patients with progressive incurable conditions who
      may require assistance with sleep for many weeks as their condition deteriorates.
      OBJECTIVES: To assess the effectiveness and safety of benzodiazepines or
      benzodiazepine receptor agonists such as Zolpidem, Zopiclone and Zaleplon for
      insomnia in palliative care. SEARCH STRATEGY: Several electronic databases were
      searched including Cochrane PaPaS Group specialized register, Cochrane Library
      Issue 4, 2001, MEDLINE, EMBASE, BNI plus, CINAHL, BIOLOGICAL ABSTRACTS, PSYCINFO,
      CANCERLIT, HEALTHSTAR, WEB OF SCIENCE, SIGLE, Dissertation Abstracts, ZETOC and
      the MetaRegister of ongoing trials. These were searched from 1960 to 2001 or as
      much of this range as possible. Additional articles were sought by handsearching
      reference lists in standard textbooks and reviews in the field and by contacting
      academic centres in palliative care and pharmaceutical companies. There were no
      language restrictions. SELECTION CRITERIA: Studies considered for inclusion were
      randomized controlled trials of adult patients in any setting, receiving
      palliative care or suffering an incurable progressive medical condition. (For
      example, cancers, AIDS, Motor Neurone Disease, Multiple Sclerosis, Parkinson's
      Disease, Chronic Obstructive Pulmonary Disease). There had to be an explicit
      complaint of insomnia in study participants, diagnosed by any of the three main
      classification systems (DSM-IV (APA 1994), ICSD (AASD 1990) or ICD (WHO 1992)),
      or as described in the study if it involved a subjective complaint of poor sleep.
      Studies had to compare a benzodiazepine or Zolpidem or Zopiclone or Zaleplon with
      placebo or active control for the treatment of insomnia. Any duration of therapy
      were considered. DATA COLLECTION AND ANALYSIS: Abstracts were independently
      inspected by both reviewers, full papers were obtained where necessary. Where
      there was uncertainty advice was sought by a third (PW). Data extraction and
      quality assessments were undertaken independently by both reviewers. MAIN
      RESULTS: No randomized controlled trials were identified meeting the a priori
      inclusion criteria. Thirty-seven studies were considered but all were excluded
      from the review. REVIEWER'S CONCLUSIONS: Despite a comprehensive search no
      evidence from randomized controlled trials was identified. It was not possible to
      draw any conclusions regarding the use of benzodiazepines in palliative care.

PMID- 12519594
TI  - Metoclopramide for migration of naso-enteral tube.
AB  - BACKGROUND: Enteral alimentation by feeding tube is a common problem and an
      efficient method of providing nutritional support to hospitalized patients with
      insufficient oral intake, but adequate gastrointestinal function. The use of
      metoclopramide, a prokinetic agent, has been recommended to achieve transpyloric
      placement, but its efficacy is controversial. OBJECTIVES: To determine the effect
      of intravenous metoclopramide on transpyloric passage of the naso-enteral tube.
      SEARCH STRATEGY: Relevant RCTs were identified by electronic search through
      MEDLINE, EMBASE, LILACS and the Cochrane Controlled Trials Register databases.
      SELECTION CRITERIA:  TYPES OF PARTICIPANTS: Adults needing enteral nutrition.
      Types of intervention: Intravenous or intramuscular metoclopramide compared to
      placebo or no intervention. Types of studies: Randomised controlled trials. Types
      of outcome measures: The success of migration of transpyloric intubation. DATA
      COLLECTION AND ANALYSIS: The reviewers evaluated the allocation concealment,
      which was classified as adequate, uncertain or inadequate. Two reviewers
      extracted the data independently. All analyses were performed according to the
      intention-to-treat method. MAIN RESULTS: Four studies were included and analysed.
      There was no statistically significant difference between intravenous or
      intramuscular metoclopramide administered to promote the tube migration (OR 0.65,
      95% CI 0.33 to 1.28). Intravenous metoclopramide 10 mg (OR 0.68, 95% CI 0.37 to
      1.23) and 20 mg (OR 0.27, 95% CI 0.01 to 10.84) were equally ineffective in
      facilitating transpyloric intubation. REVIEWER'S CONCLUSIONS: Four studies were
      included and analysed. There was no statistically significant difference between
      intravenous or intramuscular metoclopramide administered to promote the tube
      migration (OR 0.65, 95% CI 0.33 to 1.28). Intravenous metoclopramide 10 mg (OR
      0.68, 95% CI 0.37 to 1.23) and 20 mg (OR 0.27, 95% CI 0.01 to 10.84) were equally
      ineffective in facilitating transpyloric intubation.

PMID- 12519595
TI  - Physical exercise for sleep problems in adults aged 60+.
AB  - BACKGROUND: The prevalence of sleep problems in adulthood increases with age.
      While not all sleep changes are pathological in later life, severe disturbances
      may lead to depression, cognitive impairments, deterioration of quality of life,
      significant stresses for carers and increased healthcare costs. The most common
      treatment for sleep disorders (particularly insomnia) is pharmacological. The
      efficacy of non-drug interventions has been suggested to be slower than
      pharmacological methods, but with no risk of drug-related tolerance or
      dependency. Physical exercise, taken regularly, may promote relaxation and raise
      core body temperature in ways that are beneficial to initiating and maintaining
      sleep. OBJECTIVES: To assess the efficacy of physical exercise amongst older
      adults (aged 60 and above). SEARCH STRATEGY: We searched: MEDLINE (1966 - October
      2001); EMBASE (1980 - January 2002), CINAHL ( 1982 - January 2002; PsychINFO 1887
      to 2002; The Cochrane Library (Issue 1, 2002); National Research Register (NRR
      [2002]). Bibliographies of existing reviews in the area, as well as of all trial
      reports obtained, were searched. Experts in the field were consulted. SELECTION
      CRITERIA: Randomised controlled trials of physical exercise for primary insomnia
      where 80% or more of participants were over the age of 60. Participants must have
      been screened to exclude those with dementia and/or depression. DATA COLLECTION
      AND ANALYSIS: Abstracts of studies identified in searches of electronic databases
      were read and assessed to determine whether they might meet the inclusion
      criteria. Data were analysed separately depending on whether results had been
      obtained subjectively or objectively. MAIN RESULTS: One trial, including 43
      participants with insomnia, examined the effectiveness of exercise in a
      population within an elderly population. At post-treatment, sleep onset latency
      improved slightly for both men and women. Total sleep duration, sleep onset
      latency and scores on a scale of global sleep quality showed significant
      improvement. Improvements in sleep efficiency were not significant. In some cases
      improvements indicated falls to below what are usually considered pathological
      levels but the wide confidence intervals and small sample size indicate that
      these findings must be interpreted with caution. REVIEWER'S CONCLUSIONS: When the
      possible side-effects of standard treatment (hypnotics) are considered, there is
      an argument to be made for clinical use of alternative treatments in the elderly.
      Exercise, though not appropriate for all in this population, may enhance sleep
      and contribute to an increased quality of life. Research involving exercise
      programmes designed with the elderly in mind is needed.

PMID- 12519596
TI  - Splenectomy versus conservative management for acute sequestration crises in
      people with sickle cell disease.
AB  - BACKGROUND: Acute splenic sequestration crises are a complication of sickle cell
      disease, with high mortality rates and frequent recurrence in survivors of first
      attacks. Splenectomy and blood transfusion, with their consequences, are the
      mainstay of long term management used in different parts of the world.
      OBJECTIVES: To assess whether splenectomy (total or partial) to prevent acute
      splenic sequestration crises in people with sickle cell disease improved survival
      and decreased morbidity in patients with sickle cell disease, as compared with
      regular blood transfusion. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group specialist trials register which comprises
      references identified from comprehensive electronic database searches, hand
      searching relevant journals and hand searching abstract books of conference
      proceedings Additional randomized controlled trials were sought from the
      reference lists of the studies found and reviews identified by the search
      strategy. Date of the most recent search: December 2001 SELECTION CRITERIA: All
      randomized or quasi-randomized controlled trials comparing splenectomy (total or
      partial) to prevent recurrence of acute splenic sequestration crises to no
      treatment or blood transfusion in people with sickle cell disease. DATA
      COLLECTION AND ANALYSIS: No trials of splenectomy for acute splenic sequestration
      were found. MAIN RESULTS: No trials of splenectomy for acute splenic
      sequestration were found. REVIEWER'S CONCLUSIONS: Splenectomy, if full, will
      prevent further sequestration and if partial, may reduce the recurrence of acute
      splenic sequestration crises but there is lack of evidence from trials that it
      improves survival and decreases morbidity in sickle cell disease. There is a need
      for a well-designed, adequately powered randomised controlled trial to assess the
      benefits and risks of splenectomy compared to transfusion programmes as a means
      of improving survival and decreasing mortality from ASS in people with sickle
      cell disease.

PMID- 12519597
TI  - Drugs for preventing red blood cell dehydration in people with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease is an inherited disorder of haemoglobin, which
      results in abnormal red blood cells. These can deform and cause blockages in
      blood vessels, leading to acute crises such as pain, stroke and splenic
      sequestration, and chronic organ and tissue damage. Recently research has begun
      to focus on therapies which prevent the red blood cells deforming by reducing the
      loss of water and ions from the cells. However, little is known about the
      effectiveness and safety of such drugs. OBJECTIVES: To assess the relative risks
      and benefits of drugs which aim to prevent sickle cell related crises by reducing
      red blood cell dehydration. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group specialist register which comprises
      references identified from comprehensive electronic database searches,
      handsearching relevant journals and handsearching abstract books of conference
      proceedings. Date of the most recent search of the Group's specialised register:
      December 2001. SELECTION CRITERIA: All those randomised or quasi-randomised
      controlled trials of drugs which aim to prevent sickle cell crises by reducing
      red cell dehydration, compared to placebo or an alternative treatment. DATA
      COLLECTION AND ANALYSIS: Both reviewers independently selected trials for
      inclusion, assessed trial quality and extracted data from the included studies.
      MAIN RESULTS: Of the 27 trials identified, two met the inclusion criteria. The
      two trials tested the effectiveness of zinc sulphate and piracetam to prevent
      sickle cell related crises in a total of 246 patients. A reduction in pain crises
      was shown in the piracetam study over one year (weighted mean difference (WMD) 
      1.9 (95% CI -3.01, -0.79)), although blood counts were not significantly changed.
      The zinc trial showed a significant reduction in the total number of pain,
      haemolytic, aplastic and sequestration crises over one and a half years (WMD 
      2.83 (95% CI -3.51, -2.15)), but our analysis was limited by non-reporting of
      standard deviations for some data. Changes to red cell parameters and blood
      counts were inconsistent. No serious adverse events were noted in either trial.
      REVIEWER'S CONCLUSIONS: While the results of both zinc and piracetam for reducing
      sickle related crises are encouraging, larger, and/or longer term multicentre
      trials over a number of years are needed to evaluate the effectiveness of these
      therapies for patients with sickle cell disease.

PMID- 12519598
TI  - Naloxone for narcotic-exposed newborn infants.
AB  - BACKGROUND: Naloxone, a specific opiate antagonist, is available for the
      management of newborn infants with respiratory depression that may be due to
      transplacentally-acquired opiates. However, it is unclear which groups of newborn
      infants may benefit from this therapy, and whether naloxone has any harmful
      effects. OBJECTIVES: In newborn infants who have been exposed trans-placentally
      to narcotics, does naloxone reduce the need for, or duration of, ventilatory
      support or neonatal unit admission. SEARCH STRATEGY: The standard search strategy
      of the Cochrane Neonatal Review Group was used. This included electronic searches
      of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002),
      MEDLINE (1966 - February 2002), EMBASE (1988 - February 2002), and previous
      reviews including cross references. SELECTION CRITERIA: Randomised controlled
      trials comparing the administration of naloxone versus placebo, or no drug, or
      another dose of naloxone, to newborn infants with suspected or confirmed trans
      placental exposure to narcotics. DATA COLLECTION AND ANALYSIS: Data were
      extracted using the standard methods of the Cochrane Neonatal Review Group, with
      separate evaluation of trial quality and data extraction by each author and
      synthesis of data using relative risk, risk difference and weighted mean
      difference. MAIN RESULTS: We found nine trials that compared the effects of
      naloxone versus placebo or no drug in newborn infants exposed to maternal
      narcotic analgesia prior to delivery. The main outcomes reported were measures of
      respiratory function in the first six hours of life. Although we found some
      evidence that naloxone increases alveolar ventilation, we did not find any data
      on the pre-specified primary outcomes of this review: the need for assisted
      mechanical ventilation or admission to a neonatal unit. REVIEWER'S CONCLUSIONS:
      There is a need for a randomised controlled trial to determine if naloxone
      confers any clinically important benefits to newborn infants with respiratory
      depression that may be due to trans-placentally acquired narcotic.

PMID- 12519599
TI  - Combined vitamin B6-magnesium treatment in autism spectrum disorder.
AB  - BACKGROUND: The use of mega-vitamin intervention began in the early 1950's with
      the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used
      with children diagnosed with "autism syndrome" when speech and language
      improvement was observed in some children as a result of large doses of B6. A
      number of published studies attempted to assess the effects of vitamin B6-Mg (Mg
      was found to reduce undesirable side effects from B6) on a variety of
      characteristics such as verbal communication, non-verbal communication,
      interpersonal skills, and physiological function, in individuals with autism.
      OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for
      treating social, communication and behavioural responses of children and adults
      with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register
      (Cochrane Library, Issue 2, 2002), MEDLINE (1966- January 2002), EMBASE (1980
      January 2002), PsychINFO (1887 - January 2002), Dissertation Abstracts
      International (1861 - January 2002). The search engine FirstSearch was also used
      (January 2002). Reference lists for all the obtained studies and other review
      articles were examined for additional studies. SELECTION CRITERIA: All studies in
      which the participants were randomly allocated prior to intervention and in which
      outcomes were compared to either a placebo or non-treated group were included.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential
      studies identified as indicated above for inclusion. MAIN RESULTS: Two trials
      were included in the review. Both studies used a double-blind crossover design.
      One study (Tolbert 1993) provided insufficient data to conduct an analysis. The
      senior author was contacted for supporting data but was unable to provide the
      needed information. The remaining study (Findling, 1997) yielded no significant
      differences between treatment and placebo group performances following the B6
      intervention on measures of social interaction, communication, compulsivity,
      impulsivity, or hyperactivity. REVIEWER'S CONCLUSIONS: Due to the small number of
      studies, the methodological quality of studies, and small sample sizes, no
      recommendation can be advanced regarding the use of B6-Mg as a treatment for
      autism.

PMID- 12519600
TI  - Intravascular brachytherapy for peripheral vascular disease.
AB  - BACKGROUND: International treatment of atherosclerotic narrowed and blocked
      arteries involves either bypassing the blockage using a graft, widening it from
      the inside with a balloon, a procedure known as percutaneous transluminal
      angioplasty (PTA), or providing a strut to hold the vessel open, known as a
      stent. All of these treatments are however limited by the high numbers that fail
      within a year. Intravascular brachytherapy (IVBT) is the application of radiation
      directly to the site of vessel narrowing. It is known to inhibit the processes
      that lead to restenosis (narrowing) of vessels and grafts after treatment.
      OBJECTIVES: The objective of this review was to assess the efficacy and
      complications of intravascular brachytherapy on maintaining patency after
      angioplasty or stent insertion in native vessels or bypass grafts of the iliac or
      infrainguinal arteries. SEARCH STRATEGY: The reviewers searched the Cochrane
      Peripheral Vascular Diseases Group Trials Register (last searched 5 July 2002),
      the Cochrane Controlled Trials Register (last searched Issue 2, 2002), MEDLINE,
      EMBASE and reference lists of relevant articles. SELECTION CRITERIA: Randomised
      trials of the use of brachytherapy as an adjunct to the treatment of patients
      with peripheral arterial diseases (PAD) or stenosed bypass grafts of the iliac or
      infrainguinal arteries arteries versus the procedure without brachytherapy. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. Adverse events information was collected from the trials. MAIN
      RESULTS: One trial was identified which met the inclusion criteria, involving 117
      patients, mean age 71 years (43-89). The trial compared PTA versus PTA and IVBT
      in patients with long-segment de novo or restenotic lesions or occlusions of any
      length in the femoropopliteal artery. Results were provided at six month follow
      up in 107 patients (54 PTA alone, 53 PTA+IVBT). The results favoured adjuvant
      IVBT in preventing restenosis/occlusion with an odds ratio (OR) of 0.35 (95% CI
      0.24 to 0.53). Analysis of subgroups showed a significant benefit of IVBT in non
      diabetics, OR 0.22 (95% CI 0.07 to 0.69), in those undergoing IVBT in restenotic
      lesions, OR 0.32 (95% CI 0.10 to 1.01), occlusive lesions, OR 0.19 (95% CI 0.06
      to 0.62) and lesions in which the PTA length was greater than 10cm, OR 0.24 (95%
      CI 0.09 to 0.62). REVIEWER'S CONCLUSIONS: Results from the only trial available
      would suggest that IVBT is effective at improving the patency of femoropopliteal
      arteries undergoing PTA in the short-term, particularly in non-diabetics with
      long occlusions (>10cm).

PMID- 12519601
TI  - Deep transverse friction massage for treating tendinitis.
AB  - BACKGROUND: Deep transverse friction massage (DTFM) is one of several
      physiotherapy interventions suggested for the management of tendinitis pain.
      OBJECTIVES: To assess the efficacy of DTFM for treating tendinitis. SEARCH
      STRATEGY: We searched the MEDLINE, EMBASE, HealthSTAR, Sports Discus, CINAHL, the
      Cochrane Controlled Trials Register, PEDro, the specialized registry of the
      Cochrane musculoskeletal group and the Cochrane field of Physical and Related
      Therapies up to the end of June 2002. The reference list of the trials and key
      experts in the area were also consulted for additional studies. SELECTION
      CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials
      (CCTs) comparing therapeutic ultrasound with control or another active
      intervention in patients with all types of tendinitis, such as iliotibial band
      friction syndrome and extensor carpi radialis tendinitis (i.e. tennis elbow or
      lateral epicondylitis or lateralis epicondylitis humeri), were selected. DATA
      COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included
      based upon the inclusion and exclusion criteria (LB, VR). Data were independently
      abstracted by two reviewers (VR, LB), and checked by a third reviewer (BS) using
      a pre-developed form of the Cochrane Musculoskeletal Group. The two reviewers,
      using a validated checklist, assessed the methodological quality of the RCTs and
      CCTs independently. The pooled analysis was performed using weighted mean
      differences (WMDs) for continuous outcomes. MAIN RESULTS: One RCT included
      patients with ITBFS. DTFM combined with rest, stretching exercises, cryotherapy
      and therapeutic ultrasound was compared to the control group (rest, stretching
      exercises, cryotherapy and therapeutic ultrasound only). This trial showed no
      statistical difference in the three types of pain relief measured after four
      consecutive sessions of DTFM combined with other physiotherapy modalities for
      runners. There was a clinically important relative percentage difference in pain
      while running of 22%. A RCT on ECRT showed no statistical difference in pain
      relief, grip strength and the three types of functional status measured after 9
      consecutive sessions within 5 weeks of DTFM compared with other physiotherapy
      modalities. REVIEWER'S CONCLUSIONS: DTFM combined with other physiotherapy
      modalities did not show consistent benefit over the control of pain, or
      improvement of grip strength and functional status for patients with ITBFS or for
      patients with ECRT. These conclusions are limited by the small sample size of the
      included RCTs. No conclusions can be drawn concerning the use or non use of DTFM
      for the treatment of ITBFS. Future trials, utilizing specific ITBFS methods and
      adequate sample sizes are needed, before conclusions can be drawn regarding the
      specific effect of DTFM on tendinitis.

PMID- 12519602
TI  - Cervical cap versus diaphragm for contraception.
AB  - BACKGROUND: The cervical cap and the diaphragm are vaginal barrier contraceptive
      methods that prevent pregnancy by covering the cervix. The two devices also act
      as a reservoir for spermicide. The cervical cap is smaller and can remain in
      place longer than the diaphragm. Two types of cervical caps, the Prentif cap and
      the FemCap, have been compared to the diaphragm in randomized controlled trials.
      OBJECTIVES: The review seeks to evaluate the contraceptive efficacy, safety,
      discontinuation, and acceptability of the cervical cap with that of the
      diaphragm. SEARCH STRATEGY: We searched MEDLINE, Popline, Cochrane Controlled
      Trials Register, EMBASE, and LILACS for randomized controlled trials of cervical
      caps, and we reviewed the references of the included publications. Also, we wrote
      to the manufacturers and known investigators to request information about any
      other published or unpublished trials not found in our search. SELECTION
      CRITERIA: All randomized controlled trials in any language comparing a cervical
      cap with a diaphragm were eligible for inclusion. DATA COLLECTION AND ANALYSIS:
      All titles and abstracts located in the literature searches were assessed, and
      articles identified for inclusion were independently abstracted by two reviewers.
      Data were entered and analyzed with RevMan 4.1, and a second reviewer verified
      the data entered. Outcome measures include contraceptive efficacy, safety,
      discontinuation, and acceptability. Outcomes were calculated as Peto odds ratios
      with 95 percent confidence intervals using women as the denominators. Life-table
      and Kaplan-Meier cumulative rate ratios for selected measures were also presented
      in "Additional Tables." MAIN RESULTS: The Prentif cap was comparable to the
      diaphragm in preventing pregnancy, but the FemCap was not as effective in
      preventing pregnancy as its comparison diaphragm. The curves for the life-table
      cumulative pregnancy rates through 24 months for the Prentif cap and the
      diaphragm were not statistically significantly different (p-value of 0.39).
      However, the six-month Kaplan-Meier cumulative pregnancy rates for the FemCap and
      the diaphragm did not meet the a priori definition of clinical equivalence. The
      Prentif cap had a higher proportion of Class I to Class III cervical cytologic
      conversions at the three-month visit than the diaphragm; the odds ratio was 2.3
      (95% CI, 1.0-5.1). The FemCap trial did not find differences in Papanicolaou
      smear results between the cap and diaphragm groups. Prentif cap users had a lower
      odds ratio of vaginal ulcerations or lacerations (0.3; 95% CI, 0.1-0.7) than
      diaphragm users. FemCap users had a higher odds ratio of blood in the device on
      removal (2.3; 95% CI, 1.3-4.1), but a lower odds ratio of urinary tract
      infections (0.6; 95% CI, 0.4-1.0) than those in the diaphragm group. In the
      FemCap trial, similar proportions of women reported liking their assigned device
      "somewhat" or "a lot" at the two-week interview. However, FemCap users were less
      likely than the diaphragm users to state that they were "probably" or
      "definitely" likely to use the device alone after completing the trial (odds
      ratio of 0.5; 95% CI, 0.3-0.7) or that they would recommend it to a friend (odds
      ratio of 0.5; 95% CI, 0.3-0.8). REVIEWER'S CONCLUSIONS: The Prentif cap was as
      effective as its comparison diaphragm in preventing pregnancy, but the FemCap was
      not. Both cervical caps appear to be medically safe.

PMID- 12519603
TI  - Debridement of diabetic foot ulcers.
AB  - BACKGROUND: Foot ulceration is thought to affect 15% of people with diabetes at
      some time in their lives. OBJECTIVES: The aim of this review is to assess the
      evidence for the effectiveness of debridement as a treatment for diabetic foot
      ulcers. SEARCH STRATEGY: Searches of electronic databases, hand searching
      journals, bibliographies and identification of unpublished work by written
      communication with recognised experts in the diabetic foot. SELECTION CRITERIA:
      Randomised controlled trials evaluating a method of debridement in the treatment
      of diabetic foot ulcers. The outcome had to include either complete healing or
      rate of healing. There was no restriction on articles/trials based on language or
      publication status. DATA COLLECTION AND ANALYSIS: Data extraction and assessment
      of study quality were undertaken by one reviewer and checked by an Editor of the
      Wounds Group. MAIN RESULTS: 5 RCTs of debridement were identified; 3 RCTs
      assessed the effectiveness of a hydrogel as a debridement method, 1 RCT evaluated
      surgical debridement and 1 RCT evaluated larval therapy. Pooling the 3 hydrogel
      RCTs suggested that hydrogels are significantly more effective than gauze or
      standard care in healing diabetic foot ulcers (absolute risk difference 0.23; 95%
      CI: 0.10,0.36). Surgical debridement and larval therapy showed no significant
      benefit in these small trials. Other debridement methods such as enzyme
      preparations or polysaccharide beads have not been evaluated in RCTs of people
      with diabetes. REVIEWER'S CONCLUSIONS: There is evidence to suggest that hydrogel
      increases the healing rate of diabetic foot ulcers. More research is needed to
      evaluate the effects of a range of widely used debridement methods and of
      debridement per se.

PMID- 12519604
TI  - Interventions for treating collagenous colitis.
AB  - BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of
      chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This
      review was performed to identify therapies for collagenous colitis that have been
      proven in randomized trials. OBJECTIVES: To determine effective treatments for
      patients with clinically active collagenous colitis. SEARCH STRATEGY: Relevant
      papers published between 1970 and January 2002 were identified via the MEDLINE,
      PUBMED, and EMBASE databases. Manual searches from the references of identified
      papers, as well as review papers on collagenous or microscopic colitis were
      performed to identify additional studies. Abstracts from major
      gastroenterological meetings were searched to identify research submitted in
      abstract form only. Finally, the Cochrane Controlled Trials Register and the
      Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were
      searched for other studies. SELECTION CRITERIA: Four randomized trials were
      identified. One trial studied bismuth subsalicylate (published in abstract form
      only), and 3 trials (2 published in abstract form only) studied budesonide in the
      therapy of collagenous colitis. DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by each author onto 2x2 tables (treatment versus placebo and
      response versus no response). For therapies assessed in one trial only, p-values
      were derived using the chi-square test. For therapies assessed in more than one
      trial, summary test statistics were derived using the Peto odds ratio and 95%
      confidence intervals. Data were combined for analysis only if the outcomes were
      sufficiently similar in definition. MAIN RESULTS: There were 9 patients with
      collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg
      tablets daily for 8 weeks). Those randomized to active drug were more likely to
      have clinical (p=0.003) and histological (p=0.003) improvement than those
      assigned to placebo. A total of 86 patients were enrolled in 3 trials studying
      budesonide (9 mg daily for 6 to 8 weeks). The pooled odds ratio for clinical
      response to treatment with budesonide was 16.79 (95% CI 7.28-38.74), with a
      number needed to treat of 2 patients. There was significant histological
      improvement with treatment in all 3 trials studying budesonide therapy.
      REVIEWER'S CONCLUSIONS: Budesonide is effective in the treatment of collagenous
      colitis. The evidence for bismuth subsalicylate is weaker, but still important.
      The roles of these and other therapies in inducing or maintaining remission (as
      opposed to clinical or histological improvement) of collagenous colitis are
      unknown.

PMID- 12519605
TI  - Interventions for replacing missing teeth: preprosthetic surgery versus dental
      implants.
AB  - BACKGROUND: Preprosthetic surgery refers to the surgical procedures that can
      modify the oral anatomy to facilitate the retention of conventional dentures.
      Osseointegrated implants offer an alternative treatment to improve denture
      retention. A denture may be connected by special attachments to implants placed
      into the jaw. OBJECTIVES: To test the null hypothesis of no difference in the
      success (patient satisfaction and morbidity) and cost effectiveness between
      conventional prostheses that require preprosthetic surgery (PPS) and implant
      retained prostheses (IRO) that do not require preprosthetic surgery, against the
      alternative hypothesis of a difference. SEARCH STRATEGY: The Cochrane Oral Health
      Group (OHG) Specialised Register (May 2002), the Cochrane Controlled Trials
      Register (Issue 2, 2002), MEDLINE and EMBASE (May 2002) were searched. In
      addition, 55 implant companies were contacted and the bibliographies of review
      articles were checked for studies outside the hand searched journals and personal
      references were searched. SELECTION CRITERIA: Randomised controlled trials
      comparing preprosthetic surgery and implant retained dentures for improving
      denture retention. DATA COLLECTION AND ANALYSIS: Data were independently
      extracted, in duplicate, by two reviewers (HW, PC). Authors were contacted for
      details of randomisation and withdrawals and a quality assessment was carried out
      (ME, PC). The Cochrane OHG's statistical guidelines were followed. MAIN RESULTS:
      One study, containing 60 participants, reported in four articles was identified
      for inclusion in this review. No studies were excluded. There was a statistically
      significant difference between mean patient satisfaction scores with patients in
      the IRO group being more satisfied in general at both year one (WMD = -0.66(95%
      CI; -1.28 to -0.04)) and five years (WMD = -0.90(95%CI; -1.74 to -0.06). Altered
      sensation of the lower lip and chin was measured at one year and five years.
      There was no statistically significant difference at either time point and no
      patients had altered sensation at five years. REVIEWER'S CONCLUSIONS: There is
      weak evidence from the results of one randomised controlled trial including 60
      subjects that patients are generally less satisfied with preprosthetic surgery
      and a conventional denture than with an implant retained denture. There is a need
      for more well designed trials comparing the success and cost-effectiveness of
      preprosthetic surgery and implant supported dentures. Such trials should be
      reported according to the CONSORT guidelines (http://www.consort-statement.org/).
      However, since preprosthetic surgery is considered to be an obsolete treatment
      nowadays, almost completely replaced by dental implants, it may be that new RCTs
      on this topic will not be designed.

PMID- 12519606
TI  - Interferon for interferon nonresponding and relapsing patients with chronic
      hepatitis C.
AB  - BACKGROUND: Interferon monotherapy leads to sustained virologic clearance in a
      minority of patients with chronic hepatitis C. Studies have yielded conflicting
      results regarding retreatment with interferon in nonresponders and relapsers.
      OBJECTIVES: To assess the beneficial and harmful effects of retreatment with
      interferon in chronic hepatitis C nonresponders and relapsers to previous
      interferon treatment. SEARCH STRATEGY: Trials were identified through electronic
      databases, manual searches, authors, and pharmaceutical companies (August 2001).
      SELECTION CRITERIA: Randomised trials comparing interferon versus control or
      different interferon regimens in chronic hepatitis C patients being nonresponders
      and relapsers to previous interferon were included. DATA COLLECTION AND ANALYSIS:
      The primary outcome was failure to achieve a sustained virologic response defined
      as positive serum hepatitis C virus RNA at least six months following treatment.
      Secondary outcomes included liver-related morbidity, mortality, biochemical
      responses, adverse events, and histology. MAIN RESULTS: Ten randomised trials
      involving 686 nonresponders and eight trials involving 484 relapsers were
      included; their methodological quality was poor. In nonresponders, interferon
      reduced the risk of not achieving an end of treatment biochemical response
      compared with no treatment (relative risk [RR] 0.77, 95% confidence interval [CI]
      0.66 to 0.91); however, virologic responses were not reported. In a post hoc
      subgroup analysis, doses greater than 3 million units (MU) three times weekly
      offered no advantage compared with 3 MU three times weekly for biochemical
      sustained response. Failure to obtain a virologic sustained response was less
      likely with 48 than 24 weeks of therapy (RR 0.87, 95% CI 0.79 to 0.96). Adverse
      events did not differ significantly regardless of treatment dose or duration. In
      relapsers, none of the trials compared interferon with no treatment. In a post
      hoc analysis, doses greater than 3 MU three times weekly were no more effective
      in achieving a virologic sustained response than 3 MU three times weekly.
      Compared with 24 weeks, treatment durations of 48 weeks were less likely to fail
      to achieve a virologic sustained response (RR 0.69, 95% CI Random 0.51 to 0.95),
      but associated with more frequent dosage reduction (RR 9.07, 95% CI 1.20 to
      68.63). No data regarding clinical outcomes or histology was available in either
      patient group. REVIEWER'S CONCLUSIONS: Retreatment with interferon leads to
      sustained virologic clearance in a minority of chronic hepatitis C patients with
      nonresponse or relapse following interferon monotherapy. Treatment durations of
      48 weeks are superior to 24 weeks, but doses greater than 3 MU three times weekly
      are no more effective. No data exists regarding the effect on clinical outcomes.

PMID- 12519607
TI  - Group-based parent-training programmes for improving emotional and behavioural
      adjustment in 0-3 year old children.
AB  - BACKGROUND: Mental health problems in children are common. Research suggests that
      parenting has an important role to play in helping children to become well
      adjusted adults, and that the first few months and years of a child's life are
      especially important in establishing patterns of emotional, cognitive and social
      functioning which will in turn influence the child's future development and in
      particular, their mental health. The parent-infant relationship has been
      highlighted as being of particular importance. Parenting programmes have been
      shown to be effective in improving the mental health of children aged 3-10 years
      and the aim of the current review is to address their role in improving the
      mental of infants and toddlers. OBJECTIVES: The objectives of this review are as
      follows: a) To establish whether group-based parenting programmes are effective
      in improving the mental health of children less than three years of age b) To
      assess the role of parenting programmes in the primary prevention of mental
      health problems SEARCH STRATEGY: A range of biomedical and social science
      databases were searched including MEDLINE, EMBASE, CINAHL, PsychLIT, Sociofile,
      Social Science Citation Index, ASSIA, the Cochrane Library including SPECTR,
      CENTRAL, National Research Register (NRR) and ERIC. SELECTION CRITERIA: Only
      randomised controlled trials were included in which participants had been
      randomly allocated to an experimental or a control group, the latter being a
      waiting-list or no-treatment control group. Studies had to include at least one
      standardised instrument measuring some aspect of infant mental health. DATA
      COLLECTION AND ANALYSIS: Data were extracted by two reviewers. The included
      studies were critically appraised using a number of criteria including the method
      of allocation concealment. The treatment effect for each outcome in each study
      was standardised by dividing the mean difference in post-intervention scores for
      the intervention and treatment group, by the pooled standard deviation, to obtain
      an effect size. The results for each outcome in each study have been presented
      with 95% confidence intervals. Where appropriate the results have been combined
      in a meta-analysis using a fixed effects model. MAIN RESULTS: A total of five
      studies were included in the review. The 5 included studies provided a total of
      36 assessments of infant and toddler mental health including emotional and
      behavioural adjustment, and sleep patterns. All of the results apart from 6
      showed positive findings favouring the intervention group. While some of findings
      were non-significant, most of the effect sizes were large and the wide confidence
      intervals crossing the zero that were obtained in a number of the studies, were
      very probably due to small sample sizes. There was sufficient data from four
      studies to combine the results in a meta-analysis. The results of the meta
      analysis show a significant difference in children's emotional and behavioural
      adjustment favouring the intervention group. Overall, the limited follow-up data
      provide equivocal evidence concerning the maintenance of these effects over time.
      REVIEWER'S CONCLUSIONS: The results of this review suggest that parenting
      programmes can be effective in improving the mental health of infants and
      toddlers. There is, however, insufficient evidence to reach any firm conclusions
      regarding the role that such programmes might play in the primary prevention of
      mental health problems. The paucity of available evidence concerning the extent
      to which the short-term benefit of these programmes is maintained over time is
      also equivocal, and further research is required.

PMID- 12519608
TI  - Effect of the treatment of Type II diabetes mellitus on the development of
      cognitive impairment and dementia.
AB  - BACKGROUND: There is increasing interest in preventing cognitive impairment and
      dementia in later life. Epidemiological evidence shows a relationship between
      cognitive impairment and Type II diabetes. This association is stronger in
      patients who have been diagnosed for longer periods of time and in those who are
      on insulin therapy. There is little information on the short- and long-term
      influence of type of treatment and level of metabolic control on cognitive
      function of people with diabetes. OBJECTIVES: To assess the effects of different
      types and intensities of treatments for Type II diabetes on cognitive function.
      SEARCH STRATEGY: The Cochrane Control Trials Register, MEDLINE, EMBASE, PsycINFO,
      SIGLE LILACS and CINAHL as well as a number of ongoing trials databases were
      searched on 11 June 2002 using appropriate strategies. SELECTION CRITERIA:
      Randomized controlled trials in which different treatments for Type II diabetes
      have been compared and in which measures of cognitive function were made at entry
      and after the treatment. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed trial quality. Five trials were identified for possible
      inclusion but none of them could be included. In one, cognitive function was
      assessed before and after intensive or conventional diabetic treatment, but the
      comparison was not double-blind. The three other studies explored the effect of
      different treatments on QOL but did not include appropriate evaluation of
      cognitive function. The fifth did not report baseline data on cognitive function
      in the trial groups. MAIN RESULTS: No studies were found to be appropriate for
      inclusion in meta-analysis. REVIEWER'S CONCLUSIONS: There is no convincing
      evidence relating type or intensity of diabetic treatment to the prevention or
      management of cognitive impairment in Type II diabetes. Future research on
      treatments for diabetes should include standardized assessments of cognitive
      function as outcome measures.

PMID- 12519609
TI  - Interventions for replacing missing teeth: different types of dental implants.
AB  - BACKGROUND: Dental implants are available in different materials, shapes and with
      different surface characteristics. In particular, numerous implant surface
      modifications have been developed for enhancing clinical performances.
      OBJECTIVES: To test the null hypothesis of no difference in clinical performance
      between various root-formed osseointegrated implant types. SEARCH STRATEGY: The
      Cochrane Oral Health Group Specialised Trials Register, The Cochrane Controlled
      Trials Register, MEDLINE and EMBASE were searched. Hand searching included
      several dental journals. Bibliographies of relevant clinical trials and review
      articles were checked for studies outside the handsearched journals. In addition,
      authors of all identified trials and fifty-five oral implant manufacturers were
      contacted to find unpublished or ongoing RCTs. Two extensive personal libraries
      (ME and AJ) were consulted. The last electronic search was conducted 8th May
      2002. SELECTION CRITERIA: All randomised controlled trials of oral implants
      comparing implants with different materials, shapes and surface properties having
      a follow-up of at least one year. DATA COLLECTION AND ANALYSIS: Data were
      independently extracted, in duplicate, by two reviewers (ME & HW). Authors were
      contacted for details of randomisation and withdrawals and a quality assessment
      was carried out. The Cochrane Oral Health Group's statistical guidelines were
      followed. MAIN RESULTS: Thirty publications, representing 13 different RCTs, were
      identified. Five of these RCTs (seven publications), which reported results from
      a total of 326 patients, were suitable for inclusion in the review. Six implant
      systems were compared: Astra, Branemark, IMZ, ITI, Steri-Oss and Southern with a
      follow-up ranging from one to three years. All implants were made in commercially
      pure titanium and had different shapes and surface preparations. On a patient
      rather than per implant basis there were no statistically significant differences
      for failures and marginal bone level changes on intra-oral radiographs between
      various implant systems. REVIEWER'S CONCLUSIONS: There was no evidence that any
      of the implant systems evaluated was superior to the other. However, these
      findings are based on a few RCTs all having short follow-up periods and few
      participants. More RCTs should be conducted, with follow-up of at least five
      years and including a sufficient number of patients, to detect a true difference
      if any exists. Such trials should be reported according to the CONSORT guidelines
      (http://www.consort-statement.org/).

PMID- 12519610
TI  - Celecoxib for rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder,
      involving persistent joint inflammation. NSAIDs are used to control the symptoms
      of RA, but are associated with significant gastro-intestinal toxicity, including
      a risk of potentially life threatening gastroduodenal perforations, ulcers and
      bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib
      is a member, were developed in order to reduce the GI toxicity, but are more
      expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the
      management of RA by systematic review of available evidence. SEARCH STRATEGY: We
      searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane
      Database of Systematic Reviews, Cochrane Controlled Trials Register, National
      Research Register, NHS Economic Evaluation Database, Health Technology Assessment
      Database. The bibliographies of retrieved papers and content experts were
      consulted for additional references. SELECTION CRITERIA: All eligible randomised
      controlled trials (RCTs) were included. No unpublished RCTs were included in this
      edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted
      independently by two reviewers. Data was analysed using a fixed effects model. A
      validated checklist was used to score the quality of the RCTs. The planned
      analysis was to pool, where appropriate continuous outcomes using mean
      differences and dichotomous outcomes using relative risk ratios. This was not
      however possible due to the lack of data. MAIN RESULTS: Five RCTs were included
      (4465 participants); three of the studies also enrolled individuals with OA. The
      comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence
      reviewed suggests that celecoxib controls the symptoms of RA to a similar degree
      to that of the active comparators examined (naproxen, diclofenac and ibuprofen).
      When compared to placebo, the percentage of patients showing improvement
      according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily
      celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group;
      these were significantly different from the placebo group in which 25/85 (29%)
      improved. The six month data reviewed support a reduced rate of UGI complications
      with celecoxib but there is also evidence to suggest that these benefits may not
      be evident in the long-term and that celecoxib offers no additional benefit in
      patients who are also receiving cardio-prophylactic low dose aspirin. REVIEWER'S
      CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need
      to be balanced against the uncertainty that the short-term reduced incidence of
      upper GI complications are maintained in the long-term and its increased cost in
      comparison to traditional NSAIDs.

PMID- 12519611
TI  - Terazosin for benign prostatic hyperplasia.
AB  - BACKGROUND: Lower urinary tract symptoms associated with benign prostatic
      obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve
      these bothersome symptoms, treatment options include alpha-antagonists, also know
      as alpha-blockers. OBJECTIVES: We conducted a systematic review to evaluate the
      effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment
      of urinary symptoms associated with BPO. SEARCH STRATEGY: Trials were searched in
      computerized general and specialized databases (MEDLINE, Cochrane Library), by
      checking bibliographies, and by contacting manufacturers and researchers.
      SELECTION CRITERIA: Studies were included if they (1) were randomized trials of
      at least 1 month duration, and (2) included men with symptomatic BPO and compared
      terazosin with placebo or active controls. DATA COLLECTION AND ANALYSIS: Study,
      patient characteristics and outcomes data were extracted in duplicate onto
      standardized forms utilizing a prospectively developed protocol. The main outcome
      measure for comparing the effectiveness of terazosin with placebo or other BPO
      medications was change in urological symptoms as measured by validated symptom
      scores. Secondary outcomes included urodynamic measures. The main outcome measure
      for adverse effects was the number of men reporting side effects. We also
      evaluated the number of men withdrawing from treatment and the number withdrawing
      due to adverse effects. MAIN RESULTS: 17 studies involving 5,151 subjects met
      inclusion criteria (placebo-controlled (10); alpha-blockers (7); finasteride
      alone or in combination with terazosin as well as placebo (1); microwave therapy
      (TUMT) (1). Study duration ranged from 4-52 weeks. Mean age was 65 years and 82%
      of men were white. Baseline urologic symptom scale scores and flow rates
      demonstrated that men had moderate BPO. Efficacy outcomes were rarely reported in
      a fashion that allowed for data pooling but indicated that terazosin improved
      symptom scores and flow rates more than placebo or finasteride and similarly to
      other alpha antagonists. The pooled mean percentage improvements for the Boyarsky
      symptom score was 37% for terazosin versus 15% for placebo (n=4 studies). The
      mean percentage improvement for the American Urological Association symptom score
      (AUA) was 38% compared to 17% and 20% for placebo and finasteride, respectively
      (n = 2 studies). The pooled mean improvement in the International Prostate
      Symptom Score (IPSS) (40%) was similar to tamsulosin (43%). Peak urine flow rates
      improved greater with terazosin (22%), than placebo (11%) and finasteride (15%)
      but did not differ significantly from the other alpha-blockers. The percentage of
      men discontinuing terazosin was comparable to men receiving placebo and
      finasteride but was greater then with other alpha-antagonists. Adverse effects
      were greater than placebo and included dizziness, asthenia, headache and postural
      hypotension. REVIEWER'S CONCLUSIONS: The available evidence suggests that
      terazosin improves urinary symptoms and flow measures associated with BPO.
      Effectiveness is superior to placebo or finasteride, similar to other alpha
      blockers but less than TUMT. Adverse effects were generally mild but more
      frequent than other alpha-blockers and associated with between a two-four fold
      increase in treatment discontinuation.

PMID- 12519612
TI  - Water for wound cleansing.
AB  - BACKGROUND: Various solutions have been recommended for cleansing wounds, however
      normal saline is favoured as it is an isotonic solution and does not interfere
      with the normal healing process. Tap water is commonly used in the community for
      cleansing wounds because it is easily accessible, efficient and cost effective,
      however, there is an unresolved debate about its use. OBJECTIVES: The objective
      of this review was to assess the effects of water compared to other solutions for
      wound cleansing. SEARCH STRATEGY: Randomised and quasi-randomised controlled
      trials were identified by electronic searches of Cochrane Wounds Group
      Specialised Trials Register, MEDLINE, EMBASE, CINAHL, and the Cochrane Controlled
      Trials Register. Primary authors, company representatives and content experts
      were contacted to identify eligible studies. Reference lists from included trials
      were also searched. SELECTION CRITERIA: Randomised and quasi randomised
      controlled trials that compared the use of water with other solutions for wound
      cleansing were eligible for inclusion. Additional criteria were outcomes that
      included objective or subjective measures of wound infection or healing. DATA
      COLLECTION AND ANALYSIS: Trial selection, data extraction and quality assessment
      were carried out independently by two reviewers and checked by a third reviewer.
      Differences in opinion were settled by discussion. Some data were pooled using a
      random effects model. MAIN RESULTS: Three trials were identified that compared
      rates of infection and healing in wounds cleansed with water and normal saline,
      two compared cleansing with no cleansing and one compared procaine spirit with
      water. There were no standard criteria for the assessment of wound infection
      across the trials which limited the ability to pool the data. The major
      comparisons were water vs normal saline, and tap water vs no cleansing. For
      chronic wounds, the odds of developing an infection when cleansed with tap water
      compared with normal saline was 0.16, 95 % Confidence Interval (CI) 0.01, 2.96.
      Use of tap water to cleanse acute wounds was associated with a lower rate of
      infection than saline (OR 0.52, 95 % CI 0.28, 0.96). No statistically significant
      differences in infection rates were seen when wounds were cleansed with tap water
      or not cleansed at all (OR 1.06, 95 % CI 0.06, 17.47). Similarly there was no
      difference in the infection rate in wounds cleansed with water or procaine spirit
      and those cleansed with isotonic saline, distilled water and boiled water (OR
      0.55, 95 % CI 0.18,1.62). REVIEWER'S CONCLUSIONS: Although the evidence is
      limited one trial has suggested that the use of tap water to cleanse acute wounds
      reduces the infection rate and other trials conclude that there is no difference
      in the infection and healing rates between wounds that were not cleansed and
      those cleansed with tap water and other solutions. However the quality of the tap
      water should be considered prior to its use and in the absence of potable tap
      water, boiled and cooled water as well as distilled water can be used as wound
      cleansing agents.

PMID- 12519613
TI  - Single dose dipyrone for acute renal colic pain.
AB  - BACKGROUND: Renal colic pain is extremely painful and requires immediate
      treatment with strong analgesics. Dipyrone is the most popular non-opioid first
      line analgesic in many countries but in others it has been banned (e.g. USA, UK)
      because of its association with blood dyscrasias such as agranulocytosis. Since
      dipyrone is used in many countries (e.g. Brazil, Spain) there is a need to
      determine the benefits and harms of its use to treat renal colic pain.
      OBJECTIVES: To assess quantitatively the analgesic efficacy and adverse effects
      of single-dose dipyrone in adults with moderate to severe renal colic pain.
      SEARCH STRATEGY: Published reports were identified from electronic databases
      (MEDLINE, EMBASE, the Cochrane Library, LILACS) and additional studies were
      identified from the reference lists of retrieved reports. Date of the most recent
      search: January 2000. SELECTION CRITERIA: Inclusion criteria were: full journal
      publication; RCT with a double-blind design; adult patients with baseline renal
      colic pain of moderate or severe intensity; treatment arms which included
      dipyrone (oral, intramuscular or intravenous administration) and a control;
      single dose data. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain
      relief data were extracted and converted into dichotomous information to yield
      the number of patients with at least 50% pain relief over 15-30 minutes, 1-2
      hours and six hours. The proportion of patients with at least 50% pain relief was
      calculated. Single dose adverse effect data were collected. MAIN RESULTS: Eleven
      studies with 1053 patients (550 on dipyrone) met the inclusion criteria.
      Unfortunately, few data were available for analysis; most analyses were based on
      the results of single, small trials and statistical pooling of the results was
      inappropriate. Efficacy estimates were calculated as the weighted mean percent of
      patients achieving at least 50% pain relief with the range of values from trials
      contributing to the analysis. However, these estimates were not robust. Commonly
      reported adverse effects with intravenous dipyrone were dry mouth and somnolence,
      and one study reported pain at the injection site. Insufficient information was
      available for safety analyses to be conducted. REVIEWER'S CONCLUSIONS: Limited
      available data indicated that single dose dipyrone was of similar efficacy to
      other analgesics used in renal colic pain, although intramuscular dipyrone was
      less effective than diclofenac 75 mg. Combining dipyrone with antispasmolytic
      agents did not appear to improve its efficacy. Intravenous dipyrone was more
      effective than intramuscular dipyrone. Dry mouth and somnolence were commonly
      reported with intravenous dipyrone. None of the studies reported agranulocytosis.

PMID- 12519614
TI  - Frequency of administration of recombinant human erythropoietin for anaemia of
      end-stage renal disease in dialysis patients.
AB  - BACKGROUND: Although the benefits of recombinant human erythropoietin (rHu EPO)
      administration in dialysis patients have been demonstrated the optimal frequency
      regimen has not as yet been established. Treatment with rHu EPO is expensive,
      there is therefore a need for optimising the efficiency of its administration.
      OBJECTIVES: The objectives of this review were to assess the effects of different
      frequency regimens of rHu EPO administration in dialysis patients in terms of i)
      effectiveness (correction of anaemia, quality of life and freedom from adverse
      events) ii) efficiency (optimal resource use) of different rHu EPO dose regimen
      policies. SEARCH STRATEGY: We searched MEDLINE (1980 to May Week 3 2001), EMBASE
      (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October
      1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996),
      SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14th consolidation,
      September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997),
      IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant
      articles. We contacted biomedical companies and investigators in the field and we
      hand searched Kidney International (including all supplements but excluding all
      conference proceedings except for 1994) July 1983 to May 1997 inclusive. The
      Internet was also searched on: August 1997. We had also identified some studies
      from a previous broad search for all randomised controlled trials (RCTs) relevant
      to the management of end-stage renal disease. Date of the most recent search:
      June 2001. SELECTION CRITERIA: All randomised or quasi randomised controlled
      trials comparing different frequencies of rHu EPO administration in dialysis
      patients. Subgroup analyses were performed comparing haemodialysis and CAPD
      patients and also subcutaneous and intravenous administration. DATA COLLECTION
      AND ANALYSIS: Only published data were used. Data were abstracted by a single
      investigator on to a standard form. The data abstracted were relevant to the
      predetermined outcome measures: measures of correction of anaemia, rHu EPO dose,
      quality of life measures, adverse events, number of withdrawals from study,
      mortality. Where appropriate, a summary relative risk (RR) was calculated for
      dichotomous data and a weighted mean difference (WMD) or standardised mean
      difference (SMD) for continuous data. MAIN RESULTS: Eight studies met our
      inclusion criteria. When once a week administration was compared with twice
      weekly there was no significant difference in the ability to maintain the target
      haemoglobin (RR 1.00, 95% CI 0.42 to 2.40). Mean haemoglobin after twelve weeks
      of therapy was not different between the two groups (WMD -0.21g/dl, 95% CI -0.98
      to 0.56). No difference was found in mean haemoglobin or haematocrit at the end
      of any studies which compared once with thrice weekly administration of rHu EPO
      (SMD -0.31, 95% CI -0.67 to 0.06). A single study which compared once with more
      that thrice weekly administration showed no significant difference in mean
      haemoglobin at the end of the maintenance phase (mean difference -0.2g/dl, 95% CI
      -0.65 to 0.25). The dosage of erythropoietin required by those on haemodialysis
      receiving rHu EPO once weekly was just significantly more (WMD 12.0 U/kg, 95% CI
      0.24 to 23.76) than those receiving it twice weekly but the confidence interval
      is wide. No such difference was found for CAPD patients nor when the results were
      combined (WMD 5.15 U/kg, 95% CI -3.74 to 14.05). The result was not significant
      when comparing once weekly with thrice weekly administration (WMD 10.00 U/kg, 95%
      CI -80.87 to 100.87). There was no difference in the frequency of adverse events
      between any of the groups studies. REVIEWER'S CONCLUSIONS: There is no
      significant difference between once weekly versus thrice weekly subcutaneous
      administration of rHu EPO. Once weekly administration of rHu EPO would require an
      additional 12U/kg/week for patients on haemodialysis, however this is based on
      one very small study. The cost of this additional hRu EPO nee, however this is
      based on one very small study. The cost of this additional hRu EPO needs to
      assessed, in particular with regard to patient preference and compliance.

PMID- 12519615
TI  - Anti-cholinergic bronchodilators versus beta2-sympathomimetic agents for acute
      exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Inhaled bronchodilators form the mainstay of treatment for acute
      exacerbations of COPD. Two types of agent are used routinely, either singly or in
      combination: anticholinergic agents and beta2-sympathomimetic agonists.
      OBJECTIVES: To assess the effect of anti-cholinergic agents on lung function and
      dyspnea in patients with acute exacerbations of COPD, compared with placebo or
      short-acting beta-2 agonists. SEARCH STRATEGY: A comprehensive search of the
      literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD
      Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium.
      References listed in each included trial were searched for additional trial
      reports. SELECTION CRITERIA: Studies were included if the participants were adult
      patients with a known diagnosis of COPD and had symptoms consistent with criteria
      for acute exacerbation of COPD. All randomized controlled trials that compared
      inhaled ipratropium bromide or oxitropium bromide to appropriate controls were
      considered. Appropriate control treatments included placebo, other
      bronchodilating agents, or combination therapies. Studies of acute asthma or
      ventilated patients were excluded. DATA COLLECTION AND ANALYSIS: All trials that
      appeared to be relevant were assessed by two reviewers who independently selected
      trials for inclusion. Differences were resolved by consensus. MAIN RESULTS: Four
      trials compared the short-term effects of ipratropium bromide vs. a beta2
      agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant
      difference between beta2-agonist and ipratropium bromide treated patients. The
      differences were similar among the studies and when combined: Weighted Mean
      Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There
      was no significant additional increase in change in FEV1 on adding ipratropium to
      beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours)
      of the ipratropium bromide and beta2-agonist treatment combination were similar:
      WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant
      changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist,
      although one showed an increase in PaO2 in subjects receiving ipratropium bromide
      at 60 minutes. Adverse drug reactions included dry mouth and tremor. REVIEWER'S
      CONCLUSIONS: There was no evidence that the degree of bronchodilation achieved
      with ipratropium bromide was greater than that using a short-acting beta2
      agonist. The combination of a beta2-agonist and ipratropium did not appear to
      increase the effect on FEV1 more than either used alone.

PMID- 12519616
TI  - Regular treatment with long acting beta agonists versus daily regular treatment
      with short acting beta agonists in adults and children with stable asthma.
AB  - BACKGROUND: Selective beta-adrenergic agonists for use in asthma are: short
      acting (2-6 hours) and long acting (>12 hours). There has been little controversy
      about using short acting beta-agonists intermittently, but long acting beta
      agonists are used regularly, and their regular use has been controversial.
      OBJECTIVES: To determine the benefit or detriment of treatment with regular short
      or long acting inhaled beta-agonists in chronic asthma. SEARCH STRATEGY: A
      search was carried out using the Cochrane Airways Group register. Bibliographies
      of identified RCTs were searched for additional relevant RCTs. Authors of
      identified RCTs were contacted for other published and unpublished studies.
      SELECTION CRITERIA: All randomised studies of at least two weeks duration,
      comparing a long acting inhaled beta-agonist given twice daily with any short
      acting inhaled beta-agonist of equivalent bronchodilator effectiveness given
      regularly in chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers
      performed data extraction and study quality assessment independently. Authors of
      studies were contacted for missing data. MAIN RESULTS: 31 studies met the
      inclusion criteria, 24 of parallel group and 7 cross over design. Salmeterol
      xinafoate was used as long acting agent in 22 studies and formoterol fumarate in
      9. Salbutamol was the short acting agent used in 27 studies and terbutaline in 5.
      The treatment period was over 2 weeks in 29 studies, and at least 12 weeks in 20.
      25 studies permitted a variety of co-intervention treatments, usually inhaled
      corticosteroid or cromones. One study did not permit inhaled corticosteroid. Long
      acting beta-agonists were significantly better than short acting for a variety of
      lung function measurements including morning PEF (Weighted Mean Difference (WMD)
      33 l/min 95% CI 25, 42) or evening PEF (WMD 26 l/min 95% CI 18, 33); and had
      significantly lower scores for day and night time asthma symptom scores and
      percentage of days and nights without symptoms. They were also associated with a
      significantly lower use of rescue medication both during the day and night. Risk
      of exacerbations was not different between the two types of agent, but most
      studies were of short duration which limits the power to test for such
      differences. REVIEWER'S CONCLUSIONS: Long acting inhaled beta-agonists have
      advantages across a wide range of physiological and clinical outcomes for regular
      treatment.

PMID- 12519617
TI  - Oral theophylline for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Oral theophylline has, for many years, been used as a bronchodilator
      in patients with COPD. Despite the introduction of new drugs, and its narrow
      therapeutic index, theophylline is still recommended for COPD treatment.
      OBJECTIVES: To determine the effectiveness of oral theophylline when compared to
      placebo in patients with stable COPD. SEARCH STRATEGY: The Cochrane Airways
      Review Group and Cochrane Controlled Clinical Registers were searched. SELECTION
      CRITERIA: All studies were randomised controlled trials (RCTs). DATA COLLECTION
      AND ANALYSIS: Data were independently abstracted and the methodological quality
      assessed by two reviewers. MAIN RESULTS: Twenty RCTs met the inclusion criteria.
      Concomitant therapy varied from none to any other bronchodilator plus
      corticosteroid (oral and inhaled). The following outcomes were significantly
      different when compared to placebo. FEV1 improved with treatment: Weighted Mean
      Difference (WMD) 100 ml; 95% Confidence Interval (95%CI) 40, 160 ml. Similarly
      for FVC: WMD 210 ml 95%CI 100, 320. Two studies reported an improvement in
      VO2max; WMD 195 ml/min, 95%CI 113,27). At rest, PaO2 and PaCO2 both improved with
      treatment (WMD 3.2 mmHg; 95%CI = 1.2, 5., and WMD -2.4 mmHg; 95%CI = -3.5, -1.2,
      respectively). Walking distance tests did not improve (4 studies, Standardised
      Mean Difference 0.30, 95%CI -0.01, 0.62), neither did Visual Analogue Score for
      breathlessness isn two small studies (WMD 3.6, 95%CI -4.6, 11.8). The Relative
      Risk (RR) of nausea was greater with theophylline (RR 7.7; 95%CI 1.5, 39.9).
      However, patients' preference for theophylline was greater than that for placebo
      (RR 2.27; 95%CI = 1.26, 4.11). Very few patient withdrew from these studies for
      any reason. REVIEWER'S CONCLUSIONS: Theophylline has a modest effect on FEV1 and
      FVC and slightly improves arterial blood gas tensions in moderate to severe COPD.
      These benefits were seen in patients receiving a variety of different concomitant
      therapies. Improvement in exercise performance depended on the method of testing.
      There was a very low dropout rate in the studies that could be included in this
      review, which suggests that recruited patients may have been known by the
      investigators to be theophylline tolerant. This may limit the generalisability of
      these studies.

PMID- 12519618
TI  - Surgical treatment options for carpal tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome is a common disorder, for which several
      surgical treatment options are available. However, there is no consensus on the
      most effective method of treatment. OBJECTIVES: To compare the efficacy of the
      various surgical techniques in relieving symptoms and promoting return to work
      and/or activities of daily living and to compare the occurrence of side-effects
      and complications in patients suffering from carpal tunnel syndrome. SEARCH
      STRATEGY: We conducted computer-aided searches of the Cochrane Controlled Trials
      Register (Cochrane Library, Issue 1, 2000), MEDLINE(searched January 1966-March
      2000) and EMBASE (searched January 1988-February 2000), and tracked references in
      bibliographies. SELECTION CRITERIA: Randomised controlled trials comparing
      various surgical techniques for the treatment of carpal tunnel syndrome. DATA
      COLLECTION AND ANALYSIS: Study selection, assessment of methodological quality
      and data abstraction were performed by two reviewers independently of each other.
      MAIN RESULTS: Sixteen studies were included in the review. The methodological
      quality of the trials was fair to good. However, the application of allocation
      concealment was mentioned explicitly in only two trials. Many studies failed to
      present the results in sufficient detail to enable statistical pooling. Pooling
      was also impeded by the vast variety of outcome measures that were applied in the
      various studies. None of the existing alternatives to standard open carpal tunnel
      release seem to offer better relief from symptoms in the short- or long-term.
      There is conflicting evidence about whether endoscopic carpal tunnel release
      results in earlier return to work and/or activities of daily living than open
      carpal tunnel release. REVIEWER'S CONCLUSIONS: There is no strong evidence
      supporting the need for replacement of standard open carpal tunnel release by
      existing alternative surgical procedures for the treatment of carpal tunnel
      syndrome.

PMID- 12519619
TI  - Short versus long duration infusions of paclitaxel for any adenocarcinoma.
AB  - BACKGROUND: Paclitaxel has become a standard drug used in a number of common
      cancers. At first long infusions were used to reduce the rate of inflow of the
      drug and as a result reduce the occurrence of hypersensitivity types of allergic
      reactions. Trials with shorter durations of infusion, and using a cocktail of
      anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were
      begun. These were interpreted as showing that effectiveness of treatment was not
      lessened by a short infusion time. These studies also appeared to show that some
      important toxicities were less common with short infusions and that they were
      more convenient for the patient and the hospital. OBJECTIVES: To assess the
      effect of varying the duration of infusion of paclitaxel on its anti-cancer
      effectiveness and side-effects. SEARCH STRATEGY: Electronic searches of the
      Cochrane Gynaecological Cancer CRG, the Cochrane Register of Controlled Trials,
      MEDLINE, EmBase, CANCERLIT, PDQ, Meta-register (mRCT) and the M.D. Anderson
      Cancer Centre, GOG were carried out. Information from the manufacturer and
      authors of reports of studies was also acquired. SELECTION CRITERIA: The review
      was restricted to randomised controlled trials of single agent paclitaxel or
      paclitaxel with other drugs, where the only variable was the duration of
      paclitaxel infusion. The review only included patients with advanced
      adenocarcinoma. DATA COLLECTION AND ANALYSIS: Data was extracted by two
      independent reviewers and where there was disagreement this was resolved by
      discussion. Where possible the data was synthesised in a meta-analysis. MAIN
      RESULTS: Three hour paclitaxel infusions appear to result in a smaller fall in
      white blood cell count, less fever, infection and sore mouth than 24 hour
      infusions. In contrast, 24 hour infusions cause less nerve toxicity. Other side
      effects are not dependent on the duration of infusion. Evidence from individual
      trials suggesting efficacy may be slightly greater with 24 hour infusions is
      inconclusive. Combination of data from trials of different cancer sites in a meta
      analysis must be considered speculative, but the combined data also suggest that
      24 hour infusions of paclitaxel may be slightly more effective. REVIEWER'S
      CONCLUSIONS: This review confirms that, apart from neurological effects, three
      hour infusion of paclitaxel causes significantly less side effects than 24 hour
      infusion. Insufficient data exists to state whether varying the duration of
      infusion has a significant effect on its anti-cancer effectiveness. Further study
      would be required to establish whether there genuinely is a significant
      difference in efficacy according to the duration of infusion of paclitaxel.

PMID- 12519620
TI  - Chemotherapy for high-grade glioma.
AB  - BACKGROUND: Trials on the effect of systemic chemotherapy on survival and
      recurrence in adults with high-grade glioma have had inconclusive results. We
      undertook a systematic review and meta-analysis to assess the effects of such
      treatment on survival and recurrence. OBJECTIVES: To compare radiotherapy plus
      chemotherapy with radiotherapy alone in completely resected adults with high
      grade glioma. To investigate whether or not pre-defined patient subgroups benefit
      more or less from chemotherapy. SEARCH STRATEGY: MEDLINE and CancerLit searches
      were supplemented with information from trial registers and by hand searching
      relevant meeting proceedings and by discussion with relevant trialists and
      organisations. These searches were carried out in June 1997, June 1999 and
      December 2000. SELECTION CRITERIA: Trials comparing radiotherapy versus
      radiotherapy + chemotherapy were eligible for inclusion provided that they
      randomized adult patients using a method which precluded prior knowledge of
      treatment assignment. DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis
      using updated information from individual patients from all available randomized
      trials was carried out. Data from all patients randomized in all eligible trials
      were sought directly from those responsible. Updated information on survival and
      date of follow-up were obtained, as were details of treatment allocation, date of
      randomization, age, sex, histological cell type, stage and performance status. To
      avoid potential bias, information was requested for all randomized patients
      including those who had been excluded from the investigators' original analyses.
      All analyses were done on an intention to treat basis on the endpoint of
      survival. For trials using cisplatin-based regimens, subgroup analyses by age,
      sex, histological cell type, tumour stage and performance status were also done.
      MAIN RESULTS: Data from 12 randomized trials and 3004 patients were included. The
      results show a significant prolongation of survival associated with chemotherapy,
      with a hazard ratio of 0.85 (95% CI 0.78-0.91, p=0.00004) or 15% relative
      decrease in the risk of death. This is equivalent to an absolute increase in one
      year survival rate of 6% (95% confidence interval 3% to 9%) from 40% to 46% and a
      two-month increase in median survival time (95% confidence interval one month to
      three months). There was no evidence that the effect of chemotherapy was
      different in any group of patients defined by age, sex, histology, performance
      status or extent of resection. REVIEWER'S CONCLUSIONS: This small but clear
      improvement in survival from chemotherapy encourages further study of drug
      treatment of these tumours

PMID- 12519621
TI  - Terbutaline pump maintenance therapy after threatened preterm labor for
      preventing preterm birth.
AB  - BACKGROUND: Women with preterm labor that is arrested with tocolytic therapy are
      at increased risk of recurrent preterm labor. Terbutaline pump maintenance
      therapy has been given to such women to decrease the risk of recurrent preterm
      labor, preterm birth, and its consequences. OBJECTIVES: To determine the
      effectiveness and safety of terbutaline pump maintenance therapy after threatened
      preterm labor in preventing preterm birth and its complications. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group trials register (searched
      May 2002) and the Cochrane Controlled Trials Register (Cochrane Library Issue 2,
      2002). SELECTION CRITERIA: Randomized trials comparing terbutaline pump
      maintenance therapy with alternative therapy, placebo, or no therapy after
      threatened preterm labor. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the studies for inclusion and then extracted data from
      eligible studies. MAIN RESULTS: We included two studies. Terbutaline pump
      maintenance therapy did not appear to offer any advantages over the saline
      placebo pump or oral terbutaline maintenance therapy in preventing preterm births
      by prolonging pregnancy or its complications among women with arrested preterm
      labor. The weighted mean difference (WMD) for gestational age at birth was -0.1
      weeks (95% confidence interval (CI) -1.7 to 1.4) for terbutaline pump therapy
      compared with saline placebo pump for both trials combined and 1.4 weeks (95% CI 
      1.1 to 3.9) for terbutaline pump versus oral terbutaline therapy for the first
      trial. The second trial reported a relative risk (RR) of 1.17 (95% CI 0.79 to
      1.73) of preterm birth (less than 37 completed weeks) and a RR of 0.97 (95% CI
      0.51 to 1.84) of very preterm birth (less than 34 completed weeks) for
      terbutaline pump compared with saline placebo pump. Terbutaline pump therapy also
      did not result in a higher rate of therapy continuation or a lower rate of infant
      complications. No data were reported on long-term infant outcomes, costs, or
      maternal assessment of therapy. REVIEWER'S CONCLUSIONS: Terbutaline pump
      maintenance therapy has not been shown to decrease the risk of preterm birth by
      prolonging pregnancy. Furthermore, the lack of information on the safety of the
      therapy, as well as its substantial expense, argues against its role in the
      management of arrested preterm labor. Future use should only be in the context of
      well-conducted, adequately powered randomized controlled trials.

PMID- 12519622
TI  - Nonoxynol-9 for preventing vaginal acquisition of HIV infection by women from
      men.
AB  - BACKGROUND: There is a need for female-controlled methods of HIV prevention.
      Vaginal microbicides, substances inserted into the vagina to prevent women
      acquiring HIV and sexually transmitted infections (STIs) from men, could be
      useful in this regard. One potential vaginal microbicide is the widely used
      spermicide, nonoxynol-9 (N-9). OBJECTIVES: To determine the safety and
      effectiveness of N-9 in preventing vaginal acquisition of HIV infection by women
      from men. SEARCH STRATEGY: Extensive searches of electronic databases, conference
      abstracts, reference lists of relevant studies and contact with experts and
      funders. SELECTION CRITERIA: Randomised controlled trials meeting pre-determined
      quality criteria with HIV infection as the outcome. DATA COLLECTION AND ANALYSIS:
      Data were extracted by one reviewer and checked by the another. Any discrepancies
      were adjudicated by a third reviewer. MAIN RESULTS: Five trials were included in
      the review and four contributed to a meta-analysis. Overall, the risk of HIV
      infection was not statistically significantly different among women receiving N-9
      (relative risk [RR] 1.12, 95% CI 0.88-1.42; p=0.4). The risk of genital lesions
      was statistically significantly greater among women receiving N-9 (RR 1.18, 95%CI
      1.02-1.36; p=0.02). REVIEWER'S CONCLUSIONS: There is no evidence that nonoxynol-9
      protects against vaginal acquisition of HIV infection by women from men. There is
      evidence that it may do harm by increasing the frequency of genital lesions.

PMID- 12519623
TI  - Nonoxynol-9 for preventing vaginal acquisition of sexually transmitted infections
      by women from men.
AB  - BACKGROUND: The incidence and prevalence of sexually transmitted infections (STI)
      and other reproductive tract infections (RTI) is high in much of the developing
      and parts of the developed worlds. STIs and RTIs are associated with the vaginal
      transmission of HIV. Additional strategies to improve STI control are needed, and
      vaginal microbicides are a possible strategy. One potential vaginal microbicide
      is the widely used spermicide, nonoxynol-9 (N-9). OBJECTIVES: To determine the
      safety and effectiveness of N-9 in preventing vaginal acquisition of sexual
      transmitted infections (exclusive of HIV) by women from men. SEARCH STRATEGY:
      Systematic search of electronic databases, conference abstracts, reference lists
      of relevant studies and contact with experts and funders. SELECTION CRITERIA:
      Randomised controlled trials meeting pre-determined quality criteria with STI as
      the outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer
      and checked by another. MAIN RESULTS: Ten of 12 identified randomised controlled
      trials were included and findings among them were broadly consistent. In meta
      analysis, the risks of gonorrhoea (relative risk [RR] 0.91, 95%CI 0.67-1.24),
      cervical infection (RR 1.01, 0.84-1.22), trichomoniasis (RR 0.84, 0.69-1.02),
      bacterial vaginosis (0.88, 0.74-1.04), chlamydia (RR 0.88, 0.77-1.01) and
      candidiasis (RR 0.97, 0.84-1.12) were not statistically significantly different
      in women receiving N-9 compared with placebo. Genital lesions were more common in
      the N-9 users (RR 1.17, 95%CI 1.02-1.35). REVIEWER'S CONCLUSIONS: There is good
      evidence that nonoxynol-9 does not protect against sexually transmitted
      infections, and there is some evidence that it may be harmful by increasing the
      rate of genital ulceration. As such, this product cannot be recommended for STI
      prevention.

PMID- 12519624
TI  - Interventions aimed at improving immunization rates.
AB  - BACKGROUND: Immunization rates for children and adults are rising, but coverage
      levels have not reached national goals. As a result of low immunization rates,
      vaccine-preventable diseases still occur. In an era of increasing complexity of
      immunization schedules, rising expectations about the performance of primary
      care, and large demands on primary care physicians, it is important to understand
      and promote interventions that work in primary care settings to increase
      immunization coverage. A common theme across immunization programs in all nations
      involves the challenge of determining the denominator of eligible recipients
      (e.g., all children who should receive the measles vaccine), and identifying the
      best strategy to ensure high vaccination rates. Strategies have focused on
      patient-oriented interventions (e.g., patient reminders), provider interventions,
      and system interventions. One intervention strategy involves patient
      reminder/recall systems. OBJECTIVES: Assess the effectiveness of patient
      reminder/recall systems in improving immunization rates, and compare the effects
      of various types of reminders in different settings or patient populations.
      SEARCH STRATEGY: A systematic search was performed using MEDLINE (1966-1998) and
      4 other bibliographic databases: EMBASE, PsychINFO, Sociological Abstracts, and
      CAB Abstracts. Authors also performed a search of EPOC in April 2001 to update
      the review. Two authors reviewed the lists of titles and abstracts, and used the
      inclusion criteria to mark potentially relevant articles for full review. The
      reference lists of all relevant articles and reviews were back searched for
      additional studies. Publications of abstracts, proceedings from scientific
      meetings, and files of study collaborators were also searched for references.
      SELECTION CRITERIA:  STUDY DESIGN: Randomized controlled trials (RCT), controlled
      before and after studies (CBA), and interrupted time series (ITS) studies written
      in English. TYPES OF PARTICIPANTS: Health care personnel who deliver
      immunizations and children (birth to 18 years) or adults (18 years and up) who
      receive immunizations in any setting. Types of interventions: Any intervention
      that falls within the Effective Practice and Organization of Care Group (EPOC)
      scope and that includes patient reminder and/or recall in at least one arm of the
      study. Types of outcome measures: Immunization rates, or the proportion of the
      target population up-to-date on recommended immunizations. Outcomes were
      acceptable for either individual vaccinations (e.g., influenza vaccination) or
      standard combinations of recommended vaccinations (e.g., all recommended
      vaccinations by a specific date or age). DATA COLLECTION AND ANALYSIS:  DATA
      COLLECTION: Each study was read independently by two reviewers. Disagreements
      between reviewers were resolved by a formal reconciliation process to achieve
      consensus. ANALYSIS: Results are presented for individual studies as relative
      rates for randomized controlled trials, and as absolute changes in percentage
      points for controlled before and after studies. Pooled results were presented
      using the random effects model. MAIN RESULTS: Patient reminder/recall systems
      were effective in improving immunization rates in 33 of 41 included studies,
      irrespective of baseline immunization rates, patient ages, type of setting, or
      type of vaccination. Increases in immunization rates due to reminders were in the
      range of 5 to 20 percentage points. Reminders were effective for childhood
      vaccinations (OR=2.02, 95% CI =1.49,2.72), childhood influenza vaccinations
      (OR=4.19, 95% CI =2.07,8.49), adult pneumococcus or tetanus (OR=5.14, 95%CI =
      1.21, 21.8), and adult influenza vaccinations (OR=2.29, 95%CI = 1.69, 3.10).
      While reminders were most effective in academic settings (OR = 3.33, 95% CI =
      1.98, 5.58), they were also highly effective in private practice settings
      (OR=1.79, 95% CI = 1.45, 2.22) and public health clinics (OR = 2.09, 95% CI =
      1.42, 3.07). All types of reminders were effective (postcards, letters, telephone
      or autodialer calls), with telephone being the most effective but most costly.
      REVIEWER'S CONCLUSIONS: Patient reminder/recall systems in primary care settings
      are effective in improving immunization rates.

PMID- 12519625
TI  - Antidepressants for treating depression in dementia.
AB  - BACKGROUND: The use of antidepressants for patients with dementia accompanied by
      depressive symptoms is widespread, but their clinical efficacy is uncertain. Many
      of the individual trials of antidepressants have been too small to provide
      precise estimates of the moderate benefits that might realistically be expected.
      Combining the information from all appropriate trials may provide a better
      estimate of the likely effects of treatment.Objectives To determine whether
      antidepressants are clinically effective and acceptable for the treatment of
      patients with depression and also dementia.Search methods The CDCIG Specialized
      Register was last searched on 27 April 2005. This register contains records from
      major health care databases and many ongoing trials databases and is updated
      regularly.Medical information departments of pharmaceutical companies were asked
      to search their databases for any relevant clinical trials. Where necessary
      authors of trials were approached with requests for additional
      information.Selection criteria All relevant unconfounded, double-blind,
      randomized trials comparing any antidepressant drug with placebo, for patients
      diagnosed as having dementia and depression, according to established
      criteria.Data collection and analysis Two reviewers extracted data independently
      and settled any differences by agreement.Main results There were seven included
      studies with a total of 1140 subjects of which 769 met inclusion criteria. Four
      included studies reported sufficiently detailed results to enter into meta
      analyses, with a total of 137 subjects. Two of these studies investigated the
      properties of drugs not commonly used in this population with only two studies
      (Petracca 2001 and Lyketsos 2003) using the more common selective serotonin
      reuptake inhibitors (SSRIs). Lyketsos 2003 produced two significant differences
      in favour of treatment in the Cornell Scale for Depression in Dementia (CSDD) at
      12 weeks and in the psychiatrists' global rating. However, the CSDD was not used
      in any of the other studies and no statistical differences were found with the
      other measures used in the meta-analysis. The meta-analysis of the number of
      patients suffering at least one adverse event, one event of the nervous system,
      one event of the gastrointestinal system and one event of dry mouth at 6 to 12
      weeks showed a significant difference in favour of placebo. There were no other
      significant results.Authors' conclusions Available evidence offers weak support
      to the contention that antidepressants are effective for patients with depression
      and dementia.However, only four studies are included in the meta-analysis
      relating to efficacy, and sample sizes are small.Moreover, only two included
      studies investigated the properties of the more commonly used SSRIs and no
      studies investigated the properties of newer classes of antidepressants (e.g.
      selective noradrenergic reuptake inhibitors). This review draws attention to the
      paucity of research and evidence in this area.

PMID- 12519626
TI  - The application of confocal microscopy to the study of liposome adsorption onto
      bacterial biofilms.
AB  - Confocal laser scanning microscopy has been used to visualise the adsorption of
      fluorescently labelled liposomes on immobilised biofilms of the bacterium
      Staphylococcus aureus. The liposomes were prepared with a wide range of
      compositions with phosphatidylcholines as the predominant lipids using the
      extrusion technique. They had weight average diameters of 125 +/- 5 nm and were
      prepared with encapsulated carboxyfluorescein. Cationic liposomes were prepared
      by incorporating dimethyldioctadecylammonium bromide (DDAB) or 3, beta [N-(N1,N1
      dimethylammonium ethane)-carbamoyl] cholesterol (DC-chol) and anionic liposomes
      were prepared by incorporation of phosphatidylinositol (PI). Pegylated cationic
      liposomes were prepared by incorporation of DDAB and 1,2
      dipalmitoylphosphatidylethanolamine-N-[polyethylene glycol)-2000]. Confocal laser
      scanned images showed the preferential adsorption of the fluorescent cationic
      liposomes at the biofilm-bulk phase interface which on quantitation gave
      fluorescent peaks at the interface when scanned perpendicular (z-direction) to
      the biofilm surface (x-y plane). The biofilm fluorescence enhancement (BFE) at
      the interface was examined as a function of liposomal lipid concentration and
      liposome composition. Studies of the extent of pegylation of the cationic
      liposomes incorporating DDAB, on adsorption at the biofilm-bulk phase interface
      were made. The results demonstrated that pegylation inhibited adsorption to the
      bacterial biofilms as seen by the decline in the peak of fluorescence as the
      mole% DPPE-PEG-2000 was increased in a range from 0 to 9 mole%. The results
      indicate that confocal laser scanning microscopy is a useful technique for the
      study of liposome adsorption to bacterial biofilms and complements the method
      based on the use of radiolabelled liposomes.

PMID- 12519627
TI  - Liposomal daunorubicin overcomes drug resistance in human breast, ovarian and
      lung carcinoma cells.
AB  - Multi-drug resistance due in part to membrane pumps such as P-glycoprotein (Pgp)
      is a major clinical problem in human cancers. We tested the ability of
      liposomally-encapsulated daunorubicin (DR) to overcome resistance to this drug. A
      widely used breast carcinoma cell line originally selected for resistance in
      doxorubicin (MCF7ADR) was 4-fold resistant to DR compared to the parent MCF7
      cells (IC50 79 nM vs. 20 nM). Ovarian carcinoma cells (SKOV3) were made resistant
      by retroviral transduction of MDR1 cDNA and selection in vinblastine. The
      resulting SKOV3MGP1 cells were 130-fold resistant to DR compared to parent cells
      (IC50 5700 nM vs. 44 nM). Small-cell lung carcinoma cells (H69VP) originally
      selected for resistance to etoposide were 6-fold resistant to DR compared to H69
      parent cells (IC50 180 nM vs. 30 nM). In all three cases, encapsulation of DR in
      liposomes as Daunoxome (Gilead) did not change the IC50 of parent cells relative
      to free DR. However, liposomal DR overcame resistance in MCF7ADR breast carcinoma
      cells (IC50 20 nM), SKOV3MGP1 ovarian carcinoma cells (IC50 237 nM) and H69VP
      small-cell lung carcinoma cells (IC50 27 nM). Empty liposomes did not affect the
      IC50 for free DR in the three resistant cell lines, nor did empty liposomes
      affect the IC50 for other drugs that are part of the multi-drug resistance
      phenotype (etoposide, vincristine) in lung carcinoma cells. These data indicate
      the possible value of liposomal DR in overcoming Pgp-mediated drug resistance in
      human cancer.

PMID- 12519628
TI  - The transfection of Jurkat T-leukemic cells by use of pH sensitive
      immunoliposomes.
AB  - A gene transfer vector has been developed utilising anionic liposomes as a
      carrier of plasmid DNA (pEGlacZ, 7.6 kb) to transfect CD3+ T lymphocytes (Jurkat
      cells). The plasmid DNA that contained the Escherichia coli beta-galactosidase
      reporter gene was condensed using poly-l-lysine of molecular mass 20,700 (PLK99)
      to form a polyplex which was interacted with several anionic liposome
      formulations to form lipopolyplexes. The liposome formulations where based on
      dioleoylphosphatidylethanolamine (DOPE) in combination with cholesterol and
      dioleoylphosphatidylcholine (DOPC) and oleic acid, or
      dimyristoylphosphatidylethanolamine (DMPE). For targeting to the Jurkat cells
      distearoylphosphatidylethanolamine (DSPE) linked to poly (ethylene glycol)
      molecular mass 2,000 and coupled to anti-CD3 antibody was incorporated. The
      polyplexes and lipopolyplexes were characterised in terms of size, zeta
      potential, agarose gel electrophoresis and electron microscopy and the
      permeability of the lipopolyplexes to liposome-encapsulated glucose was
      determined. The polyplexes consisted of a mixed population of rod-like structures
      (53-160 nm long and 23-31 nm diameter) and spheres (18-30 nm diameter). The
      lipopolyplexes retained a permeability barrier although were more permeable to
      glucose than their component liposomes. The poly-l-lysine condensing agent was
      still susceptible to pronase digestion suggesting that the polyplex was
      associated with the outer surface of the liposome. The lipopolyplexes with lipid
      composition DOPE/cholesterol/OA/DSPE-PEG2000 anti-CD3+ PLK99-plasmid DNA had
      significant gene transfer activity, as monitored by beta-galactosidase
      expression, that depended on the charge ratio of the component polyplex and the
      lipid/DNA weight ratio. The anti-CD3 antibody, the liposomal lipid and pH
      sensitivity were essential for transfection activity.

PMID- 12519629
TI  - The influence of cholesterol and charge on the membrane domains of
      alkylphospholipid liposomes as studied by EPR.
AB  - Alkylphospholipids are physiologically active derivatives of lipids effective in
      the treatment of breast cancer. Among them, octadecyl-(1,1-dimethyl-4-piperidino
      4-yl)-phosphate (OPP) was demonstrated recently to have the strongest antitumor
      effect in micellar as well as in sterically stabilised liposome suspension with a
      low cholesterol content. In this work electron paramagnetic resonance (EPR) was
      used to study the influence of cholesterol, charge, and sterical stabilisation by
      PEG2000DSPE on the domain structure and fluidity characteristics of the membrane
      of OPP liposomes. As a spin probe 5-doxylpalmitoyl methyl ester was used. By
      computer simulation of the EPR spectra it was found that the experimental spectra
      are composed of three spectral components, which were attributed to three types
      of domains with different fluidity characteristics. The EPR parameters as well as
      the proportions of the individual domains were found to be mainly dependent on
      the amount of cholesterol, and only to a minor degree on charge and sterical
      stabilisation. There was a pronounced increase in the proportion of membrane
      domains with low order parameter, when the molar ratio of cholesterol to OPP was
      decreased below 1. At the same time the order parameters of all domains
      decreased, pointing to a transition from a less to a more fluid membrane
      organisation. These results coincide with an improved therapeutic activity of
      formulations with a low molar ratio of cholesterol to OPP and indicates that the
      fluidity characteristics of the membrane may be important for the effectiveness
      of liposomal alkylphospholipids against breast cancer cells.

PMID- 12519630
TI  - Safety of archaeosome adjuvants evaluated in a mouse model.
AB  - Archaeosomes, liposomes prepared from the polar ether lipids extracted from
      Archaea, demonstrate great potential as immunomodulating carriers of soluble
      antigens, promoting humoral and cell mediated immunity in the vaccinated host.
      The safety of unilamellar archaeosomes prepared from the total polar lipids (TPL)
      of Halobacterium salinarum, Methanobrevibacter smithii or Thermoplasma
      acidophilum was evaluated in female BALB/c mice using ovalbumin (OVA) as the
      model antigen. Groups of 6-8 mice were injected (0.1 mL final volume)
      subcutaneously at 0 and 21 days, with phosphate buffered saline (PBS), 11 microg
      OVA in PBS, 1.25 mg of antigen-free archaeosomes in PBS (ca 70 mg/kg body wt), or
      PBS containing 11-20 microg OVA encapsulated in 1.25mg archaeosomes. Animals were
      monitored daily for injection site reactions, body weight,temperature and
      clinical signs of adverse reactions. Sera were collected on days 1, 2, 22, and 39
      for analyses of creatine phosphokinase. Mice were sacrificed on 39 d, sera were
      collected for biochemical analyses, and major organs (liver, spleen, kidneys,
      heart, lungs) were weighed and examined macroscopically. There were no
      indications of adverse reactions or toxicity associated with any of the
      archaeosome adjuvants. None of the antigen-free archaeosomes elicited significant
      anti lipid antibodies when subcutaneously injected (1 mg each at 0, 1, 2, and 4
      weeks) in mice, although anti H. salinarum lipid antibodies were detected. These
      antilipid antibodies cross-reacted with the TPL of T. acidophilum archaeosomes
      but not with the TPL of M. smithii archaeosomes nor with lipids of ester
      liposomes made from L-alpha-dimyristoylphosphatidylcholine (DMPC), L-alpha
      dimyristoylphosphatidylglycerol (DMPG), and cholesterol (CHOL). In vitro
      hemolysis assay on mouse erythrocytes indicated no lysis with M. smithii or T.
      acidophilum archaeosomes at up to 2.5 mg/mL concentration. At this concentration,
      H. salinarum archaeosomes and DMPC/DMPG/CHOL ester liposomes caused about 2% and
      4% hemolysis, respectively. Based on this mouse model evaluation, archaeosomes
      are well-tolerated and appear relatively safe for potential vaccine applications.

PMID- 12519632
TI  - Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate
      toxicity.
AB  - Paraoxonase (PON1) is an A-esterase capable of hydrolysing the active metabolites
      (oxons) of a number of organophosphorus (OP) insecticides such as parathion,
      diazinon and chlorpyrifos. PON1 activity is highest in liver and plasma, and
      among animal species significant differences exist, with birds and rabbits
      displaying very low and high activity, respectively. Human PON1 has two
      polymorphisms in the coding region (Q192R and L55M) and five polymorphisms in the
      promoter region. The Q192R polymorphism imparts different catalytic activity
      toward some OP substrates, while the polymorphism at position -108 (C/T) is the
      major contributor to differences in the level of PON1 expression. Animal studies
      have shown that PON1 is an important determinant of OP toxicity, with animal
      species with a low PON1 activity having an increased sensitivity to OPs.
      Administration of exogenous PON1 to rats or mice protects them from the toxicity
      of OPs. PON1 knockout mice display a high sensitivity to the toxicity of diazoxon
      and chlorpyrifos oxon, but not paraoxon. In vitro assayed catalytic efficiencies
      of purified PON(192) isoforms for hydrolysis of specific oxon substrates
      accurately predict the degree of in vivo protection afforded by each isoform. Low
      PON1 activity may also contribute to the higher sensitivity of newborns to OP
      toxicity.

PMID- 12519633
TI  - The randomized controlled trial in studies using biomarkers.
AB  - The randomized controlled trial (RCT) is a scientific experiment during which
      observations on the effects of therapy or a preventive action are conducted by
      the researcher under rigorous control. The purpose of the experiment is to clear
      the uncertainties surrounding a clinical/research issue and involves isolating
      the 'treatment' and 'end result' variables from external influences. RCTs
      therefore make use of scientific method standards: measuring, which includes the
      possibility of reproducing observations; controlling factors unconnected to the
      cause-effect relationship of interest; and the external verification or
      'falsification' of the cause-effect relationship. Many RCTs are now including
      biomarkers to answer scientific questions in a more accurate way. In the present
      methodological paper, the main aspects involved in the design and conduction of a
      trial are discussed, with special emphasis on the use of biomarkers. Aspects that
      are often overlooked by scientists involved in the design of trials include
      multiple comparisons, subgroup analysis, the duration of the observations, the
      use of surrogate endpoints, and ethical issues. This review summarizes the main
      issues that should be addressed in a protocol, and illustrates these with an
      example.

PMID- 12519634
TI  - Activities of glutamate dehydrogenase and aspartate and alanine aminotransferases
      in freshwater snails Helisoma duryi and Lymnaea natalensis exposed to copper.
AB  - In this paper we investigate the potential of glutamate dehydrogenase (GDH) and
      aspartate and alanine aminotransferases (AST and ALT) as biomarkers of water
      pollution due to copper in the freshwater snails Helisoma duryi and Lymnaea
      natalensis. Snails were dosed with copper(II) ion concentrations of 0.01, 0.1 and
      1 mg kg(-1) breeding water for a period of 96 h, after which those surviving were
      shelled. The copper content in the breeding water, in whole snail tissue and in
      the snail shells was determined at the end of the period of exposure. For enzyme
      determinations, whole snail tissue was first homogenized and fractionated by
      centrifugation at 500 g to remove the nuclei. The resulting supernatant was then
      centrifuged at 10,000 g to give a pellet fraction representing the mitochondrial
      fraction and a supernatant representing the cytosolic fraction. Copper was very
      toxic to both snail species at concentrations above 0.2 mg l(-1), with only 3% of
      the Helisoma and 12% of the Lymnaea surviving at concentrations of approximately
      1 mg l(-1). The copper content in the shells and tissues of snails rose with
      increasing copper concentration in the breeding water, and was 2.1- to 4.9-fold
      in snails exposed to copper ion at a dose of 1 mg kg(-1) water compared with
      undosed snails. Similarly, the activities of GDH and AST rose by up to 4.7-fold
      in the homogenate and the mitochondrial and cytosolic fractions with increasing
      concentrations of copper. These activities, however, fell at copper
      concentrations of approximately 1 mg l(-1), which coincided with massive death of
      snails. Mitochondrial ALT disappeared at copper ion concentrations of
      approximately 0.2 mg l(-1) for Lymnaea and 1 mg l(-1) for Helisoma, possibly
      indicating mitochondrial degeneration. These results show that GDH, AST and ALT
      have the potential to be biomarkers of sublethal copper pollution in these two
      snail species, since their activities were significantly altered by low copper
      concentrations.

PMID- 12519635
TI  - Association between the risk of coronary artery disease in South Asians and a
      deletion polymorphism in glutathione S-transferase M1.
AB  - South Asians living in Western societies show a greater risk of coronary artery
      disease (CAD) than the indigenous Caucasian population, probably related to the
      change to a Westernised lifestyle and an associated genetic susceptibility.
      Modulation of DNA damage and mutation caused by polymorphisms in detoxification
      enzymes, including the glutathione S-transferases (GSTs), is a well-established
      risk factor for tobacco-related carcinogenesis, and a similar change in cellular
      damage may be involved in the risk of vascular disease associated with tobacco
      smoking. In this study we examined whether polymorphisms in GST genes influence
      the risk of CAD in a case-control group of South Asians, following our recent
      observation of such an association in Caucasians from the same region of the UK.
      Blood was obtained from 170 patients of South Asian origin admitted for
      angiographic investigation of chest pain and from 203 controls. Patients were
      subdivided into those with and without previous acute myocardial infarction
      (AMI), and DNA was analysed for deletions in the GSTM1 and GSTT1 genes. An
      association was found between the prevalence of the GSTM1 null genotype and the
      risk of developing CAD in this study population. The frequency of the null
      genotype was 52.7% in healthy controls and 41.2% in patients (odds ratio [OR]
      0.63, 95% confidence interval [95% CI] 0.42-0.95, p = 0.029). The effect was
      similar in subjects with or without a prior history of AMI. The association was
      also independent of smoking history, with both non-smokers and smokers showing a
      similar pattern of genotype distribution, the frequency of the null genotype
      being 51.2% in controls versus 37.0% in patients in 'never' smokers (OR 0.56, 95%
      CI 0.33-0.94, p = 0.037) and 60.0% in controls versus 46.2% in patients in 'ever'
      smokers (OR 0.57, 95% CI 0.25-1.28, p = 0.223). The association remained after
      adjusting for age, sex, body mass index and the presence or absence of stenosis.
      No significant associations were observed between the GSTT1 genotype and
      cardiovascular disease (chi(2) test, p > 0.1). The results of this study indicate
      that the GSTM1 null genotype is protective against both CAD and AMI. However,
      further study is required in order to elucidate the, as yet unexplained,
      mechanisms underlying this association.

PMID- 12519636
TI  - Quantification of human intestinal gene expression profiles using exfoliated
      colonocytes: a pilot study.
AB  - Early detection of colon cancer can result in a high cure rate; therefore, an
      accurate screening method is imperative. Adoption of non-invasive testing
      designed to reduce anxiety over colorectal cancer screening and improve early
      detection is highly desirable. Therefore, we have developed a novel non-invasive
      methodology utilizing exfoliated colonocytes in order to quantify colonic
      messenger RNAs (mRNAs). Previously we have demonstrated in the rat that intact
      eukaryotic mRNA can be isolated due to the presence of exfoliated colonocytes in
      the faecal stream. To assess use of this methodology in humans, this pilot study
      evaluated exfoliated colonocyte mRNA expression of 11 putative biomarkers using
      real-time reverse transcription-polymerase chain reaction (RT-PCR) in seven
      normal subjects, four subjects with inflammation, and 10 tumour-bearing subjects
      presenting for colonoscopy. Expression of the biomarkers was evaluated following
      normalization to TATA box binding protein mRNA levels. Tumour-bearing subjects
      diagnosed with adenoma had elevated levels of cyclin Dl (p = 0.041). In addition,
      subjects displaying inflammation of the colon exhibited higher mRNA levels of
      cyclooxygenase-2 (p = 0.007). These data suggest that mRNA isolated from
      exfoliated colonocytes could be used to detect early stages of colon cancer, and
      possibly chronic inflammation. To broaden the utility of non-invasive marker
      analysis, additional studies are needed to generate a multi-target assay panel of
      diagnostic markers. This will allow for the development of robust classifiers
      that can determine critical gene sets for the diagnosis and prediction of colon
      cancer in animal models and humans.

PMID- 12519637
TI  - Use of biochemical markers to monitor changes in bone turnover in cynomolgus
      monkeys.
AB  - The ovariectomized old cynomolgus monkey is a recognized model of human
      osteoporosis, and the same species can be used for the assessment of the efficacy
      and potential toxicity of agents intended to prevent or treat osteoporosis.
      Several assays have been developed that can measure the same biochemical markers
      of bone turnover as are used in human patients for the diagnosis and treatment
      follow-up of bone-related diseases, including osteoporosis. The aim of the
      present study was to describe the results obtained with these assays in normal
      control monkeys, their variations with age and sex, and their sensitivity in
      monitoring the bone turnover induced by ovariectomy in old skeletally mature
      cynomolgus monkeys. Seven old cynomolgus monkeys were bilaterally ovariectomized
      and 13 age-matched monkeys were sham-operated. Bone mineral density and
      biochemical markers were measured before and at regular intervals after surgery
      for up to 20 months. Total alkaline phosphatase (total ALP), bone-specific
      alkaline phosphatase isoenzyme (bone ALP) and osteocalcin (OC) were highly
      correlated to the decrease in bone mineral density (BMD) induced by ovariectomy.
      Deoxypyridinoline (DPD) measured by enzyme-linked immunoassay was insensitive to
      the bone resorption induced by ovariectomy, but cross-linked N-telopeptide (NTX
      I) was higher in ovariectomized monkeys than in control monkeys. These results
      demonstrate that reliable biochemical parameters are available to adequately
      monitor and provide insight into osteoclastic bone resorption and osteoblastic
      bone formation, the two components of bone turnover in this animal model, and can
      thus be used to assess the efficacy and toxicity of potential therapeutic agents.

PMID- 12519638
TI  - Race differences in a sample of vocational rehabilitation clients with traumatic
      brain injury.
AB  - OBJECTIVE: To evaluate race differences in demographics, injury severity, and
      vocational outcomes for persons with TBI. PARTICIPANTS: Seventy-five individuals
      with TBI (13 African American, 62 Caucasian) who requested services from the
      Missouri Division of Vocational Rehabilitation (VR) over a 2-year period.
      MEASURES: Demographics (i.e. age, race, level of education), injury severity
      (i.e. LOC, PTA, length of hospitalization, neuropsychological test scores), VR
      services provided (e.g. transportation, maintenance, on-the-job training, etc.),
      and VR outcomes (successfully vs unsuccessfully employed; cost per case).
      PROCEDURE: All participants completed a standard neuropsychological evaluation
      and completed VR services (i.e. were followed from enrollment to case closure).
      HYPOTHESES: African Americans and Caucasians would not differ in demographics or
      injury severity, although fewer African Americans would be successfully employed
      through DVR. ANALYSES: Chi-squares and non-parametric MANOVAs to evaluate race
      differences in terms of demographics, injury severity, vocational services
      provided and vocational outcomes. RESULTS: As hypothesized, there were few race
      differences in demographics or injury severity, although African Americans
      received significantly more transportation services (62 vs 21%). Contrary to
      hypotheses, there was no difference in the number of successfully employed
      African Americans (23%) vs Caucasians (18%). CONCLUSIONS: African Americans and
      Caucasians with TBI achieve similar vocational successes if they receive state VR
      services.

PMID- 12519639
TI  - Reported problems and their resolution following mild, moderate and severe
      traumatic brain injury amongst children and adolescents in the UK.
AB  - PRIMARY OBJECTIVES: To examine the problems reported by families of children who
      have suffered traumatic brain injury (TBI), and how these differ from problems
      reported by control families. To identify those problems most likely to resolve
      over time, and to examine information and follow-up requirements. DESIGN, METHODS
      AND PROCEDURES: The families of 97 children with mild (49), moderate (19) and
      severe (29) TBI, aged 5-15 at injury, were interviewed and assessed at a mean of
      2.29 years post-injury and compared with 31 healthy controls. A structured
      questionnaire was used to collect information on problems pre- and post-TBI.
      Initially, respondents reported problems spontaneously, and were subsequently
      prompted using a checklist of problem categories. Problems of behaviour and
      emotion were measured using the Vineland Adaptive Behaviour Scales (VABS) and the
      Hospital Anxiety and Depression Scale (HADS). MAIN OUTCOMES AND RESULTS:
      Following the TBI, 83 children (85.6%) received no therapeutic input, 74 families
      (76.3%) had unmet information needs, particularly regarding long-term
      consequences. At first interview, 1097 problems were reported by the TBI group.
      Behavioural and school problems were frequently reported by all TBI groups,
      significantly more than controls (p < or = 0.001). On the VABS, approximately two
      thirds of children with TBI exhibited 'significant' maladaptive behaviours,
      significantly more than controls (p = 0.002). Children in the mild and
      moderate/severe groups were significantly more anxious than controls on the HADS
      (p = 0.04). At 12 month follow-up, there were no significant differences in
      problem resolution between the TBI groups: 498 (53.9%) problems remained
      unchanged and 75 (8.1%) had worsened. Physical problems were most likely to
      resolve. CONCLUSIONS: Parents should be given information and support following
      their child's TBI, children should be routinely followed-up by health
      professionals and their needs assessed. It was found that children with TBI may
      be at risk of anxiety, yet few parents reported this as a particular concern.
      Future research should examine the relationship between anxiety and TBI.

PMID- 12519640
TI  - Are there sub-types of attentional deficits in patients with persisting post
      concussive symptoms? A cluster analytical study.
AB  - AIM: The present study aimed to examine attentional deficits in patients with
      persisting post-concussive symptoms using a multi-componential framework of
      attention. DESIGN: A cross-sectional investigation using standardized tests and
      questionnaires of attention including 92 patients. METHOD: Participants were
      administered comprehensive measures of attention assessing sustained attention
      (Sustained Attention Response to Task, Backward Digit Span), selective attention
      (Stroop Word-Colour Test, Colour Trails Test), divided attention (Paced Auditory
      Serial Addition Test, Symbol Digit Modalities Test), and attentional control
      (Tower of Hanoi, Six Elements Test). Ecological tests of attention were used to
      validate the cluster solution. MAIN OUTCOME: Three clusters of patients with
      different combinations of attentional deficits were identified. They were 'mild
      sustained attentional deficits', 'selective and divided attentional deficits',
      and 'general attentional deficit'. A MANOVA indicated that these three clusters
      were statistically and clinically different from one another in terms of
      different attentional components proposed. CONCLUSION: This study provides
      preliminary evidence suggesting that sub-types of attentional impairments exit in
      patients with post-concussive symptoms.

PMID- 12519641
TI  - Community integration: a useful construct, but what does it really mean?
AB  - The primary objective of this paper is to contribute to a clearer understanding
      of the construct of community integration. Rehabilitation literature is discussed
      in relation to three measures of community integration: the AIMS Interview,
      Community Integration Measure and Community Integration Questionnaire. Results of
      a principal components analysis with varimax rotation indicated that the measures
      are independent and coherent. Significant correlations were not found between
      total scores on the three measures and problem behaviour or quality of life.
      However, analysis of individual items on the scales yielded one significant
      correlation between the first item on the Community Integration Measure (i.e.
      sense of belonging) and quality of life. The need for a clear statement in future
      research regarding the definition of community integration is emphasized, and
      inclusion of both subjective perceptions and objective indicators of community
      integration is recommended.

PMID- 12519642
TI  - Cognitive retraining in epilepsy.
AB  - Epilepsy is the commonest neurological disorder, so there is a need to establish
      more effective remedial programmes for the deficits in cognitive functioning
      associated with epilepsy. The present paper studies the relative change in the
      targeted skill areas as a consequence of cognitive retraining. For this purpose,
      a pre- and post-multiple baseline design was adopted with the intention of
      treating specific deficient skill. The measures of neuropsychological functioning
      adopted were a composite of tests/tasks, with specific emphasis on attention,
      memory and emotional status. The subject was targeted to a special neuro
      rehabilitation programme comprised of cognitive retraining, supportive therapy
      and a deep breathing relaxation exercise. A regular home intervention programme
      was conducted simultaneously. Cognitive retraining included both paper and pencil
      tasks and real life activities. The training programme covered a 6-week period
      and each weekly session lasted approximately 1 hour. The results showed an
      overall improvement in cognitive performance across sessions, and the regular
      home intervention sessions were found to have enhanced the subject's performance.
      In conclusion, it was noted that by identifying cognitive deficits, effective
      training programmes can be devised that will be of substantial benefit to
      patients with epilepsy.

PMID- 12519643
TI  - The family systems approach to treating families of persons with brain injury: a
      potential collaboration between family therapist and brain injury professional.
AB  - Although brain injury may have a great impact on the family as a whole, family
      reactions are not adequately addressed in rehabilitative programmes. When they
      are, treatment tends to be approached from a family education and support
      perspective and not from a family therapy perspective. The aim of the following
      paper is to illustrate the important role that a family systems approach can play
      in treating families of individuals with brain injury. In particular, clinical
      examples taken from the literature will be presented that illustrate how family
      roles can be modified as a consequence of a brain injury, and the importance of
      re-establishing or re-distributing these roles. It will be argued that an
      intimate collaboration between family therapist and brain injury professional is
      essential, and that the ideal professional make-up of clinicians working with
      families of persons with brain injury are those well-versed in both brain injury
      rehabilitation and family therapy.

PMID- 12519644
TI  - Parental stress and burden following traumatic brain injury amongst children and
      adolescents.
AB  - PRIMARY OBJECTIVES: To assess parental stress following paediatric traumatic
      brain injury (TBI), and examine the relationship between self-reported problems,
      parental stress and general health. RESEARCH DESIGN: Parents of 97 children
      admitted with a TBI (49 mild, 19 moderate, 29 severe) to North Staffordshire
      National Health Service Trust, and parents of 31 uninjured children were
      interviewed and assessed. METHODS AND PROCEDURES: Structured interviews were
      carried out with families, and parents assessed on the Parenting Stress Index
      (PSI/SF) and General Health Questionnaire (GHQ-12) at recruitment, and repeated
      12 months later. MAIN OUTCOMES AND RESULTS: Forty parents (41.2%) of children
      with TBI exhibited clinically significant stress. Regardless of injury severity,
      parents of injured children suffered greater stress than control parents as
      measured by the PSI/SF (p = 0.001). There was a highly significant relationship
      between number of problems reported and level of parental stress (p = 0.001).
      Financial burden was related to severity of TBI. At follow-up, one third of
      parents of children with severe TBI scored > or =18 on the GHQ-12, signifying
      poor psychological health. CONCLUSIONS: The parents of a child with serious TBI
      should be screened for abnormal levels of stress. Parental stress and family
      burden may be alleviated by improved information, follow-up and support.

PMID- 12519645
TI  - Measurement of impaired self-awareness after traumatic brain injury: a comparison
      of the patient competency rating scale and the awareness questionnaire.
AB  - PRIMARY OBJECTIVE: To compare the Patient Competency Rating Scale (PCRS) and the
      Awareness Questionnaire (AQ) in the measurement of impaired self-awareness (ISA)
      in persons with traumatic brain injury (TBI). RESEARCH DESIGN: Prospective cohort
      of patients seen for inpatient rehabilitation following TBI. PROCEDURES: Measures
      of self-awareness were collected at resolution of post-traumatic amnesia and
      outcomes (rated employability) were collected at discharge from inpatient
      rehabilitation. OUTCOMES AND RESULTS: Subjects were 129 persons with TBI.
      Measures from the PCRS and AQ showed moderate correlations. Models using as
      predictors patient/clinician discrepancies for the PCRS and the AQ performed
      comparably in predicting employability (Nagelkerke R(2) = 0.22 and 0.20,
      respectively). CONCLUSIONS: The PCRS and AQ showed only moderate correlations,
      but performed comparably as measures of ISA after TBI. Patient/clinician
      discrepancies appeared to be more valid measures of ISA early after TBI than
      patient/family discrepancies. Preliminary cutting points for severity of ISA were
      presented for the two scales.

PMID- 12519646
TI  - Brain injury and violent crime.
AB  - PRIMARY OBJECTIVE: To test the hypothesis that TBI is associated with violent
      crime, the prevalence and characteristics of traumatic brain injury (TBI) were
      compared between men convicted of domestic violence and a matched comparison
      group. METHODS AND PROCEDURES: Participants were 20 African American men
      convicted of domestic violence and 20 African American men without criminal
      convictions matched for age and socioeconomic status. Participants completed a
      questionnaire regarding health and behaviour history. MAIN OUTCOMES AND RESULTS:
      More than half of the participants in both groups had sustained a TBI, although
      injuries in the offender group were significantly more severe. There were
      significantly more reports of problems with anger management in the offender
      group. CONCLUSIONS: Published epidemiological data regarding TBI may
      underestimate the prevalence in urban populations, which may have confounded
      earlier studies of TBI and domestic violence. The reported prevalence in this
      sample of defendants suggests implications for the justice system.

PMID- 12519647
TI  - Outcome of prolonged coma following severe traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To assess the outcome of severe traumatic brain injury 1 year
      after trauma. RESEARCH DESIGN: Prospective study conducted at the neurosurgical
      department of a university hospital. METHODS AND PROCEDURES: A total of 24
      patients were included. Outcome was assessed by means of Glasgow outcome scale,
      Barthel index, Functional independence measure (FIM) and Disability rating scale
      (DRS). Need of care and job ability were also evaluated. EXPERIMENTAL
      INTERVENTIONS: Patients received multimodal early-onset stimulation and
      continuous inpatient and outpatient rehabilitation therapy. MAIN OUTCOMES AND
      RESULTS: Six patients died, three remained in a vegetative state, six were
      severely disabled, six were moderately disabled and three achieved a good
      recovery 1 year after injury. Mean Barthel index was 68.9, mean FIM was 88.3 and
      mean DRS 27.7. The majority of patients still were at least intermittently
      dependent on care. Most of the trauma survivors were unable to work. CONCLUSIONS:
      Despite intensive rehabilitation treatment, severe traumatic brain injury is
      still burdened with significant mortality and morbidity.

PMID- 12519648
TI  - Understanding outcomes based on the post-acute hospitalization pathways followed
      by persons with traumatic brain injury.
AB  - PRIMARY OBJECTIVES: To identify the factors that determine the pathways of care
      people with traumatic brain injury (TBI) follow after acute care discharge, and
      to identify differences in outcome based on those pathways. RESEARCH DESIGN:
      Telephone survey of a statewide, population-based sample of persons surviving
      through acute hospitalization for TBI. METHODS AND PROCEDURES: Included were 1059
      individuals who: (a) were discharged from acute care in 1996 and 1997; (b) were
      eligible for inclusion in the statewide, population-based TBI follow-up system,
      (c) had either a severe TBI or were among a 20% random sample with milder
      injuries, and (d) consented to participate in a 1-year post-injury follow-up
      survey. The survey included administration of the Functional Independence Measure
      (FIM), the Craig Handicap Assessment and Reporting Technique (CHART), the
      Alertness Behaviour Sub-scale of the Sickness Impact Profile (SIP), and the
      Health Status Questionnaire (HSQ-12). Medical records for all participants were
      abstracted for injury severity, pre-injury history (aetiologic and demographic)
      and discharge disposition data. Data were weighted to represent the population
      from which the sample was derived prior to analyses. MAIN OUTCOMES AND RESULTS:
      Almost 2/3 of TBI survivors in this population-based sample received no
      additional services following discharge from the acute care hospital. Six post
      acute-hospitalization pathways were identified based on combinations of inpatient
      rehabilitation, community-based services and long-term care (LTC). In each
      category--except for the one involving a discharge directly from acute care to
      home--people with the most severe TBIs were disproportionately over-represented.
      Older people and people whose care was funded by government payers were over
      represented in both care pathways involving LTC, while members of minority groups
      were under represented. Those who went to LTC had the poorest outcomes, but even
      those completing rehabilitation had relatively poor outcomes compared with those
      discharged directly to home. CONCLUSIONS: Of concern are the relatively large
      numbers of people receiving no rehabilitation and other services in all severity
      categories. Those in LTC--typically older and government funded people--reported
      the poorest outcomes. Unanswered questions remain relating to the poor perceived
      quality of life reported by those completing rehabilitation programmes. Further
      study is also needed to more fully understand the affects of such characteristics
      as gender, minority status, employment and funding sources on the care pathway
      that is followed.

PMID- 12519649
TI  - Olfactory function after mild traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to determine the incidence of olfactory
      dysfunction after mild traumatic brain injury (MTBI). Damage to the olfactory
      bulbs or frontal cortex has been reported in MTBI, but olfactory dysfunction
      after MTBI has not been studied in a prospective way before. DESIGN: Patients
      with first-time MTBI were included. Patients' olfactory threshold values
      (Hyposmia Utility Kit by Olfacto-Labs) were measured 2 weeks after the trauma.
      Associations between olfactory threshold values and individual symptoms and S
      100B and NSE concentrations were examined, using multiple linear regression
      analysis, adjusting for the influence of age. RESULTS: Twenty-two per cent of 111
      included patients had hyposmia and 4% had anosmia. Thresholds at 2 weeks showed
      no significant associations with the presence of symptoms at the ER, nor with
      early concentrations of S-100B or NSE. CONCLUSIONS: Although a high prevalence of
      olfactory dysfunction was found, no correlation was found between olfactory
      dysfunction and acute parameters of MTBI.

PMID- 12519650
TI  - EMA analysis of tongue function in children with dysarthria following traumatic
      brain injury.
AB  - PRIMARY OBJECTIVE: To investigate the speed and accuracy of tongue movements
      exhibited by a sample of children with dysarthria following severe traumatic
      brain injury (TBI) during speech using electromagnetic articulography (EMA).
      METHODS AND PROCEDURES: Four children, aged between 12.75-17.17 years with
      dysarthria following TBI, were assessed using the AG-100 electromagnetic
      articulography system (Carstens Medizinelektronik). The movement trajectories of
      receiver coils affixed to each child's tongue were examined during consonant
      productions, together with a range of quantitative kinematic parameters. The
      children's results were individually compared against the mean values obtained by
      a group of eight control children (mean age of 14.67 years, SD 1.60). MAIN
      OUTCOMES AND RESULTS: All four TBI children were perceived to exhibit reduced
      rates of speech and increased word durations. Objective EMA analysis revealed
      that two of the TBI children exhibited significantly longer consonant durations
      compared to the control group, resulting from different underlying mechanisms
      relating to speed generation capabilities and distances travelled. The other two
      TBI children did not exhibit increased initial consonant movement durations,
      suggesting that the vowels and/or final consonants may have been contributing to
      the increased word durations. CONCLUSIONS AND CLINICAL IMPLICATIONS: The finding
      of different underlying articulatory kinematic profiles has important
      implications for the treatment of speech rate disturbances in children with
      dysarthria following TBI.

PMID- 12519651
TI  - Advanced maternal age is not only associated with newborn somatometrics but also
      with the mode of delivery.
AB  - BACKGROUND: At both extremes of reproductive phase, female cycles are
      characterized by a high rate of anovulation, and pregnancies at these phases of
      reproductive span are considered as risky for obstetric complications, poor
      pregnancy outcome and increased maternal and newborn morbidity and mortality.
      AIM: To analyse if this high rate of anovulation may be interpreted as an
      adaptation to poor pregnancy outcome. Therefore the association patterns between
      maternal age and newborn somatometric characteristics and the mode of delivery
      were tested. SUBJECTS AND METHODS: The associations between the age as well as
      somatic characteristics such as pre-pregnancy weight, stature, pelvic dimensions
      and pregnancy weight gain of 10 765 women aged between 12 and 49 years (mean =
      25.3, SD = 5.7) and newborn body dimensions and the mode of delivery were
      analysed. RESULTS: With increasing maternal age, maternal and newborn body
      dimensions increased significantly. Although extremely young mothers were
      significantly shorter and lighter and exhibited the significantly lowest pre
      pregnancy weight status and the narrowest pelvic dimensions, they showed the
      lowest rates of caesarean sections (13.1%) and, unexpectedly, not the highest
      rate of low weight newborns (<2,500 g). In contrast, for mothers older than 35
      years the highest rate of low weight newborns (3.7%) and the highest rate of
      macrosom newborns (<4,000 g) were found. Furthermore, mothers older than 40 years
      experienced the significantly highest rate of caesarean section (31.3%).
      CONCLUSIONS: Special risks were found for mothers older than 35 years, so the
      lower rates of ovulatory cycles during this phase of life may be interpreted as
      an adaptation to increased risks for complications and poor pregnancy outcome.

PMID- 12519652
TI  - The characteristics of bone turnover in the second decade in relation to age and
      puberty development in healthy Japanese male and female subjects--Japanese
      Population-based Osteoporosis Study.
AB  - BACKGROUND: There are few studies that clarify the characteristics of bone
      turnover in children and adolescents. Furthermore, little has been published on
      changes in urinary CrossLaps(TM) (CTx) in Japanese subjects. AIM: To investigate
      biochemical markers of bone turnover in subjects, in relation to age and puberty
      development. SUBJECTS AND METHODS: We measured serum bone specific alkaline
      phosphatase (B-Alp) and CTx in 1207 Japanese subjects aged 9-18 years. As an
      indicator of puberty development, the age that pubic hair appeared in males and
      menstruation started in females was obtained from questionnaires. RESULTS: B-Alp
      and CTx/Cr (creatinine) had high values before and just after the indicators and
      was lower thereafter, reaching a plateau in both genders. There was no
      significant difference in these values in males 5-6 years, or 7 years and more
      after the appearance of pubic hair. B-Alp and CTx/Cr values 7 years and more
      after menarche were significantly lower than those 5-6 years after menarche,
      however the differences were relatively small. CONCLUSIONS: Subjects in the
      second decade can be divided into three groups: 'before the appearance of pubic
      hair for males and menarche for females', 'up to and including 3-4 years after
      them' and '5-6 years and more after them'.

PMID- 12519653
TI  - Areca nut, energy metabolism and hunger in Asian men.
AB  - BACKGROUND: The nut of the Areca catechu palm has long been attributed effects on
      hunger and the digestive process. OBJECTIVES: The objectives were to assess
      experimentally effects of areca nut on fasting and postprandial energy
      metabolism, substrate utilization and hunger. SUBJECTS AND METHODS: Two
      randomized, placebo-controlled, double-blind studies were undertaken. In study 1,
      eight Indian men received bioadhesive gels delivering 0, 5, 10 or 20 mg arecoline
      to the buccal sulcus after an overnight fast. Resting energy expenditure and
      substrate utilization were determined by ventilated hood calorimetry over 6 h
      during which hunger was rated on five occasions. In study 2, 15 Indian men
      received gels delivering 0 or 10 mg arecoline after consuming a 2.5 MJ meal, and
      the same protocol was then applied as in study 1. RESULTS: Fasting resting energy
      expenditures exceeded basal metabolic rate (BMR) by 5.4+/-0.8% (Mean+/-SE) after
      placebo, and 5.1+/-0.7% after 20 mg arecoline, but by 0.9+/-0.8% and 0.7+/-0.5%
      following 5 mg and 10 mg arecoline, respectively. Carbohydrate (CHO) utilization
      rates rose after areca nut compared to placebo (F(3,252)= 7.3, p< 0.001). Hunger
      varied across doses (chi(2) = 10.5, p < 0.02), being lowest after 10 mg and
      highest after 20 mg, and was influenced by interaction of dose with delta resting
      energy expenditure. In study 2, areca dose interacted with fat-free mass (FFM) to
      lower by 5.4+/-11.2% the thermic effect of a meal (F(1,28) = 4.9, p = 0.05), and
      retarded peak 'digestive-phase' thermogenesis by 60 min (F(1,58) = 5.7, p =
      0.02). Postprandial delta CHO utilization was greater (F(1,28) = 4.5, p = 0.05),
      and hunger was lower (chi:(2) = 3.8, p = 0.05), after areca nut. The areca nut
      altered relationships of hunger to thermic effects of the meal, and to delta
      substrate utilization, in ways consistent with appetite suppression. CONCLUSION:
      Areca nut constituents modulate metabolic signals regulating appetite in man.
      This concurs with customary belief.

PMID- 12519654
TI  - Ventilatory response to hypoxia in elderly women.
AB  - BACKGROUND: The respiratory system is subject to the ageing process, which could
      limit its responsiveness to stimuli. Attenuation of the ventilatory response to
      hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be
      germane to the pathogenesis of hypoxic respiratory disorders developing more
      often in elderly subjects. AIM: The study seeks to determine the potential
      adverse effects of age on the hypoxic ventilatory response by comparing this
      response in groups of elderly and young female subjects. SUBJECTS AND METHODS:
      Nineteen healthy women of the mean age of 71+/-1.3 (SE) years and 16 women in
      their twenties were required to perform a progressive isocapnic hypoxic test,
      based on the rebreathing technique. The ventilatory response was evaluated from
      the slopes of minute ventilation and mouth occlusion pressure, an index of
      inspiratory neuromuscular drive, against arterial oxygen saturation. The
      breathing pattern components also were measured with the breath-by-breath
      routine. RESULTS: Ventilatory response to hypoxia averaged 0.65+/-0.10 L/min/%
      SaO(2) and neuromuscular output was 0.012+/-0.002 kPa/% SaO(2) in the elderly
      women and these slopes were not reduced compared with those in the young. Nor did
      the ventilatory slopes relate to age in the older subjects. Baseline breathing
      pattern was modified in the elderly in that the mean inspiratory flow was
      significantly higher, but it reached the same stimulated level as that in the
      young. CONCLUSIONS: Ventilatory response to hypoxia is independent of age in
      healthy women. Thus, functional sensitivity of the respiratory control mechanisms
      does not attenuate with age.

PMID- 12519655
TI  - Influence of knowledge, training and experience of observers on the reliability
      of anthropometric measurements in children.
AB  - OBJECTIVE: To elucidate the impact of the observer's level of technical
      knowledge, training and experience with measuring height and triceps skinfold
      thickness on the reliability of these measurements in children. Despite of
      instructions and encouraging careful measurements, these factors may
      significantly affect measurements and lead to interpretation difficulties,
      especially of short term growth data. SUBJECTS AND METHODS: A cross-sectional
      study was designed in which 18 children, aged 2-7 years, were measured in duplo
      by 12 observers with different backgrounds and levels of experience, protocol
      knowledge and protocol training. The main outcome measures, precision and
      accuracy, were expressed as technical error of measurement (TEM) and average bias
      (AB) in comparison with an expert anthropometrist. RESULTS: As expected, the best
      educated and most experienced observers scored the best precision and accuracy.
      By ranking analysis and multiple regressions we learned that precision and
      accuracy in measuring height and triceps skinfold thickness are mainly predicted
      by allround knowledge of the measurement protocol (p< 0.05) and the years of
      experience (p< 0.05). A practical training course of only a few hours does not
      seem to improve reliability significantly. CONCLUSION: To get a more reliable
      insight in growth of a child it is important to be aware of the influence on
      measurement outcome values of protocol knowledge and years of experience. Growth
      studies should use detailed anthropometric standardization protocols and train
      people to acquire better insight into these protocols.

PMID- 12519656
TI  - Assessing non-linear estimation procedures for human growth models.
AB  - BACKGROUND: In the last 20 years several non-linear models with a relatively
      small number of parameters have provided useful descriptions of the complete
      human growth curve. However, some aspects of the estimation procedures used have
      not been properly studied, e.g. estimation of biases, measures of non-linearity,
      and the possibility of autocorrelated errors and heteroscedasticity. OBJECTIVES:
      To present a detailed analysis of these aspects for five well-known non-linear
      models (Preece-Baines, Shohoji-Sasaki and three models proposed by Jolicoeur et
      al.) and a large data set (the MRC Edinburgh Longitudinal Study). SUBJECTS: A
      cohort of 74 females and 103 males collected for the Edinburgh Longitudinal Study
      for the MRC Human Genetics Unit, Edinburgh, UK, comprising approximately
      quarterly height measurements for small ages and semestral height measurements
      for the remaining ages up to the early twenties. RESULTS: We found little
      evidence of extreme curvature and relatively small, cyclical patterns in the
      residuals. The estimates obtained with ordinary non-linear least squares were
      very close to those obtained with more complicated estimation procedures.
      CONCLUSIONS: The five models studied are reasonably robust against most of the
      problems encountered when fitting non-linear models to human growth data; this
      confirms some conjectures which have been taken for granted by a large number of
      authors. The presence of cyclical patterns is a consequence of the global
      description of growth attempted by these five models.

PMID- 12519657
TI  - Correlates of the age at natural menopause in Morocco.
AB  - PRIMARY OBJECTIVE: To determine the median age of natural menopause and factors
      associated with the timing of menopause in Morocco. RESEARCH DESIGN: A population
      based sample of 299 women from Rabat, Morocco were interviewed using a semi
      structured questionnaire. METHODS AND PROCEDURES: Logit analysis and logistic
      regression were used to estimate the median age and identify factors associated
      with the age at menopause. MAIN OUTCOMES AND RESULTS: The median age of natural
      menopause in Morocco is estimated to be 48.4 years (95% CI: 36.9, 70.3). Women
      who reported the onset of menstruation at age 11 or younger (OR = 2.84, 95% CI:
      1.00, 8.10) had an earlier age at menopause than women who started menstruating
      at age 12 or older. Women who had ever used oral contraceptives were more likely
      to have a later age at menopause (OR = 0.55, 95% CI: 0.30, 1.00). The length of
      time a woman used oral contraceptives influenced the timing of the menopause in
      unadjusted models but after adjusting for the age at menarche the effect was no
      longer statistically significant. Marital status, parity, education level, and
      social class were not statistically associated with the age at menopause.
      CONCLUSIONS: The estimated age at natural menopause in Morocco is 1-3 years
      earlier than the median ages reported in industrialized countries and some
      developing countries. Factors that alter the frequency of ovulation or rate of
      follicular atresia appear to be important in determining the age at menopause.

PMID- 12519658
TI  - Romantic partners' use of pornography: its significance for women.
AB  - This article addresses the question of what significance pornography viewing by
      their intimate partners has for women involved in committed relationships. In
      this report, we will (a) briefly review the only two previous studies on this
      topic, both of which were undertaken with highly distressed populations, and (b)
      present the results of a survey designed to assess the attitudes of a broader,
      more diverse population of women.

PMID- 12519661
TI  - Concordance between women's physiological and subjective sexual arousal is
      associated with consistency of orgasm during intercourse but not other sexual
      behavior.
AB  - Many studies have found a discordance between women's genital (vaginal pulse
      amplitude) and subjective sexual arousal responses to erotica. We hypothesized
      that the association between the physiological and subjective domains would be
      greater for women with greater orgasmic consistency during penile-vaginal
      intercourse but not for orgasm consistency during other sexual behaviors. We
      confirmed this specific hypothesis in a sample (N = 38) of postmenopausal women.
      In addition, we discovered that the correlation between the domains was unrelated
      to social desirability responding, that orgasm consistency was not less for
      intercourse than for other sexual activity, and that orgasm consistency during
      intercourse was uncorrelated with orgasm consistency during masturbation. We
      discuss the results in terms of the unique nature of penile-vaginal intercourse,
      our study's implications for sex therapy, and orgasm consistency during
      intercourse being an operational measure of functional vaginal sensitivity and
      sexual pleasure integration and organization.

PMID- 12519663
TI  - Couple therapy for low sexual desire: a systemic approach.
AB  - This article will illustrate how marital therapists and their supervisors can
      instructively use the Basson Sexual Response Cycle (BSRC) as a teaching and
      therapeutic tool to enable students to move their clients toward improved sexual
      relationships. Second, it will illustrate that the Basson model can be integrated
      into Emotionally Focused Martial Therapy (EFT) to track and shift the couple's
      habitual attachment pattern or circular fight. Third, it will show that by
      working the triangle of emotion and the triangle of conflict described in the
      Brief Psychodynamic Model during the second step of stages 4-6 of EFT, the couple
      therapist has a working methodology to create change at a deeper emotional level,
      when the couple's intimacy issues are complex. Two case examples will be used.

PMID- 12519665
TI  - Validation of the Female Sexual Function Index (FSFI) in women with female
      orgasmic disorder and in women with hypoactive sexual desire disorder.
AB  - The Female Sexual Functioning Index (FSFI; Rosen et al., 2000) is a self-report
      measure of sexual functioning that has been validated on a clinically diagnosed
      sample of women with female sexual arousal disorder. The present investigation
      extended the validation of the FSFI to include women with a primary clinical
      diagnosis of female orgasmic disorder (FOD; n = 71) or hypoactive sexual desire
      disorder (HSDD; n = 44). Internal consistency and divergent validity of the FSFI
      were within the acceptable range for these populations of women. Significant
      differences between women with FOD and controls and between women with HSDD and
      controls were noted for each of the FSFI domain and total scores.

PMID- 12519667
TI  - Etiological correlates of vaginismus: sexual and physical abuse, sexual
      knowledge, sexual self-schema, and relationship adjustment.
AB  - This study investigated the role of sexual and physical abuse, sexual self
      schema, sexual functioning, sexual knowledge, relationship adjustment, and
      psychological distress in 87 women matched on age, relationship status, and
      parity and assigned to 3 groups--vaginismus, dyspareunia/vulvar vestibulitis
      syndrome (VVS), and no pain. More women with vaginismus reported a history of
      childhood sexual interference, and women in both the vaginismus and VVS groups
      reported lower levels of sexual functioning and a less positive sexual self
      schema. Lack of support for traditionally held hypotheses concerning etiological
      correlates of vaginismus and the relationship between vaginismus and dyspareunia
      are discussed.

PMID- 12519669
TI  - The influence of coronary bypass graft surgery on the marital relationship and
      family functioning of the patient.
AB  - The primary aim of this study was to assess the effect of coronary bypass graft
      surgery on certain aspects of the marital relationship and on family functioning
      of patients. The secondary aim was to determine which coping strategies families
      used postoperatively. An experimental pre- and posttest research design was used.
      We collected data using the Enriching and Nurturing Relationship Issues,
      Communication and Happiness Scale, the Family Adaptability and Cohesion
      Evaluation Scale II, and the Family Crisis Oriented Personal Evaluation Scales.
      The results indicated that bypass surgery had a negative effect on the patients'
      marital satisfaction, communication, and attitudes toward the division of roles
      in the marriage and family. Bypass surgery had a further negative influence on
      the emotional bonding of the patients and their spouses with other members of the
      family. The patients' adaptability regarding new challenges facing the family was
      also affected negatively. The patients who were still working also showed a
      greater decline in some of the measured variables than the retired patients. The
      coping strategies used most often by the families were the seeking of spiritual
      support and the reframing of the problem. The results also indicated that if
      passive appraisal was used as a coping strategy, the patients' marital
      satisfaction would decrease, and if reframing of the problem was used, the
      patients' adaptability regarding new challenges facing the family would increase.

PMID- 12519679
TI  - Noise problems associated with relocating a bookstore in a gymnasium.

PMID- 12519680
TI  - EPA's exposure assessment tools and models.

PMID- 12519681
TI  - Development of a model for reducing occupational injuries.

PMID- 12519683
TI  - Development of a new respirator for organic vapors with a breakthrough detector
      using a semiconductor gas sensor.
AB  - A method for determining breakthrough of organic vapors in a respirator cartridge
      was developed. A thick film semiconductor gas sensor was used as a breakthrough
      detector. Air containing organic vapor was introduced into the cartridge, and an
      output signal from the sensor inserted in the downstream flow of the cartridge
      was recorded on an IC card. Simultaneously, the breakthrough curve was obtained
      by measuring the vapor concentration at downstream from the respirator cartridge
      with a gas chromatograph (GC) equipped with a flame ionization detector. When the
      breakthrough was almost completed, the data recorded in the card were transferred
      to a personal computer and the change in the output signal from the sensor was
      compared with the breakthrough curve obtained by the GC. Twelve organic solvents
      including aromatic hydrocarbons, chlorinated hydrocarbons, acetates, alcohols,
      ketones, and aliphatic hydrocarbons were tested under low (20%-25%) and high (70%
      80%) relative humidity ranges. The sensitivity of the sensor for chlorinated
      hydrocarbons such as 1,1,1-trichloroethane was relatively low, especially when
      the relative humidity was high, but the rise time of the sensor output signal was
      almost the same as or earlier than the breakthrough time by the GC. Based on the
      experimental results, a new respirator for organic vapors that can detect the end
      of service life was developed.

PMID- 12519684
TI  - An outbreak of hypersensitivity pneumonitis at a metalworking plant: a
      longitudinal assessment of intervention effectiveness.
AB  - The authors describe a longitudinal assessment of intervention effectiveness in
      response to an outbreak of hypersensitivity pneumonitis (HP) at a metalworking
      facility. Thirty-five (29%) of the plant's 120 production workers were given a
      clinical diagnosis of HP during the two years of the investigation. Although
      quantitative exposure assessment tools were of limited utility, the investigators
      successfully used qualitative observations and the patients' return-to-work
      experiences to iteratively evaluate their exposure control recommendations.
      Recommended interventions included improving metalworking fluid management
      practices, enclosing selected metalworking fluid machining operations,
      eliminating mist cooling, exhausting two additional water-based industrial
      processes, increasing general dilution ventilation, and worker training. As of
      November 1999, 26 months into the outbreak, 51 percent (18) of the employees with
      a clinical diagnosis of hypersensitivity pneumonitis had been able to return to
      work. The symptom onset of the 35 workers who were given a clinical diagnosis of
      hypersensitivity pneumonitis during the two-year study period predated the
      implementation of the interventions. The collaboration of a multidisciplinary
      team appears to have allowed for successful intervention in this setting. A
      specific etiological agent(s) associated with the outbreak was not confirmed
      during the investigation. An acid fast isolate identified as being in the
      Mycobacterium chelonae group was detected in only one of the submitted
      metalworking fluid (MWF) sump samples. Longitudinally, there was a statistically
      significant difference in MWF sump bacteria (X(2) = 286.4, df = 17, p <.0001) and
      MWF sump fungi (X(2) = 28.1, df = 7, p <.0002). Measured oil mist air levels did
      not exceed the Occupational Safety and Health Administration's (OSHA's)
      permissible exposure limit (PEL), and in fact, did not exceed 0.5 mg/m(3).

PMID- 12519685
TI  - Development of an HPLC method for simultaneous analysis of five antineoplastic
      agents.
AB  - Simultaneous analysis of common antineoplastic agents potentially hazardous to
      healthcare workers is of much interest for the evaluation of the overall health
      risk to these workers. Such analysis could be applied to both air and surface
      monitoring samples to provide a broader indication of risk to combinations of
      these agents. It was determined that the ability to simultaneously evaluate five
      frequently used, potentially hazardous agents was sufficient for general
      evaluation of exposures to healthcare workers. The approach used to select the
      five agents was to obtain a list of the agents used most frequently in both a
      cancer hospital and an outpatient cancer treatment center, then review the list
      to determine which agents were potentially more hazardous to human health. From
      these reviews, it was decided to attempt to develop an analytical method able to
      detect and quantify the presence of 5-fluorouracil, ifosfamide, cyclophosphamide,
      doxorubicin HCl, and paclitaxel. A reverse-phase high performance liquid
      chromatograph (HPLC) with a Waters Symmetry C8 column and a UV wavelength of 195
      nm was selected for method development. The mobile phase was 22.75 percent
      acetonitrile in water buffered to a pH of 6.0. The HPLC analytical method
      developed is able to detect all five agents of interest, and at minimum
      detectable concentrations of 0.5-microgram/mL for each of the five agents.

PMID- 12519686
TI  - A new monitoring method using solid sorbent media for evaluation of airborne
      cyclophosphamide and other antineoplastic agents.
AB  - Cyclophosphamide is a known human carcinogen. In July 1999, in a report at a
      conference on cytotoxic drugs in Sweden, it was indicated that cyclophosphamide
      (CP) was not effectively controlled by high efficiency particulate air (HEPA)
      filters.((1)) This then raised a concern that the existing air monitoring
      methods, which utilize polytetrafluoroethylene (a.k.a. PTFE, or Teflon) or glass
      fiber filters for evaluation of antineoplastics such as CP in air may also be
      ineffective for collection and quantification of such agents. It was decided that
      further evaluation of the existing filter method for monitoring antineoplastics
      in air be conducted. This evaluation determined that the filter method of
      monitoring was minimally effective for some antineoplastic agents, and that an
      alternate method of monitoring should be sought. The method subsequently
      developed utilizes a solid sorbent tube, Anasorb 708, a methacrylic acid polymer.
      Evaluation of this sorbent tube for adsorption and desorption properties found it
      had a greater than 90 percent recovery for both CP and ifosfamide. Other agents
      evaluated included 5-fluorouracil, doxorubicin, and paclitaxel. All three agents
      were able to be detected and measured by use of Anasorb 708 solid sorbent tube.
      Validation of the method was then conducted with air pulled through the tubes via
      attachment to an air manifold system at air flows ranging from 1.5 to
      approximately 4.0 liters per minute for up to 24 hours. This evaluation did
      validate the Anasorb 708 tube as an effective media for collection of airborne
      concentrations of CP from less than 1 microgram up to approximately 2 mg (2000
      microgram) per tube. This corresponds to a concentration range of approximately
      0.7 microgram/m(3) (0.0007 mg/m(3)) to 0.7 mg/m(3) in a 5.76 m(3) volume of air.
      This method can provide accurate information on airborne concentrations of CP for
      purposes of conducting risk assessments or evaluation of risk management methods.

PMID- 12519687
TI  - Results of the Massachusetts methylene chloride end-users survey.
AB  - A survey of Massachusetts companies reporting use of methylene chloride between
      1995 and 1999 was conducted to assess the status of industrial use of the
      chemical in 2000. Methylene chloride has had wide use in industry although it has
      been identified as potentially hazardous to exposed workers and the environment.
      New and tightened occupational and environmental regulations taking effect in the
      1990s were hypothesized to have reduced use of the chemical in Massachusetts.
      Substitute technologies, especially aqueous cleaning, were expected to have
      replaced methylene chloride in many industries. Seventeen of the 21 Massachusetts
      manufacturing companies reporting use of over 10,000 lb/y of methylene chloride
      between 1995 and 1999 were surveyed by telephone regarding their experiences of
      methylene chloride use and elimination and/or replacement. Fifteen of the 17
      companies had either eliminated (10) or reduced to below 10,000 lbs/yr (5) their
      use of methylene chloride at the time of the survey in 2000. Many of the surveyed
      companies moved to aqueous cleaning from methylene chloride degreasing
      operations. Environmental concerns were the most popular reason given for
      eliminating or reducing use of methylene chloride. Worker health and safety
      concerns, especially concern about compliance with the 1997 Occupational Safety
      and Health Administration methylene chloride standard, were also a motivation. In
      general, the companies associated many benefits and few problems with eliminating
      or reducing use of methylene chloride. Exposure reduction strategies based on
      toxics use reduction techniques appear to be feasible for many manufacturing
      companies. However, research should be conducted to assess the introduction of
      new hazards as a result of tightened regulations on methylene chloride.

PMID- 12519688
TI  - An evaluation of one-time professional cleaning in homes with lead-based paint
      hazards.
AB  - A key challenge in reducing the burden of lead poisoning is to identify cost
      effective interventions that minimize lead-based paint hazards. One-time
      professional cleaning of lead-contaminated dust and debris was conducted in 37
      housing units with deteriorated lead-based paint and dust lead hazards. These
      study units are a subset of a larger cohort of the nearly 3500 housing units
      enrolled in the Evaluation of the HUD Lead-Based Paint Hazard Control Grant
      Program. Dust lead loading measurements were taken prior to cleaning, immediately
      after cleaning (i.e., clearance), and six months, one, two, and three years post
      intervention. The cleaning intervention significantly reduced dust lead loadings
      on floors, windowsills, and window troughs immediately following the work.
      However, these reductions did not persist at six months and one year post
      intervention. Six months and one year post-intervention dust lead loadings are
      not significantly different from the pre-intervention loadings on either bare
      floors or windowsills. Although window trough lead loadings declined over 50
      percent from pre-intervention to one year post-intervention, the loadings
      rebounded markedly from the geometric mean at clearance of 101 microgram/ft(2) to
      5500 microgram/ft(2) at 6 months and 5790 microgram/ft(2) at one-year post
      intervention. These results demonstrate that a single professional cleaning of
      dust and debris without addressing potential sources of lead dust (such as
      deteriorated lead-based paint) or repeating the cleaning are unlikely to result
      in significant and sustained reductions in dust lead loadings. More extensive
      interventions that address deteriorated lead-based paint, although more
      expensive, are likely to provide longer term reductions in dust lead loadings.
      Cleaning strategies, however, may be useful in emergency situations to reduce
      lead dust hazards when paint repair and other lead hazard control activities
      cannot be done immediately.

PMID- 12519690
TI  - 4-Biphenylaldehyde and 9-anthraldehyde: two fluorescent substrates for
      determining P450 enzyme activities in rat and human.
AB  - 1. 4-Biphenylaldehyde (4-BA) and 9-anthraldehyde (9-AA) were examined as
      substrates for cytochrome P450 (CYPs) enzymes in rat and human. Both aldehydes
      were oxidized by CYPs to fluorescent carboxylic acids, which can be assayed with
      a high sensitivity by an easy fluorimetric method. 2. With liver microsomes from
      control and induced rats, the oxidation of both 9-AA and 4-BA followed simple
      Michaelis-Menten kinetics. Only microsomes from rats pretreated with
      phenobarbital (a strong inducer of P4502B1/2) could increase (about threefold)
      the oxidation rates (V(max)) of both aldehydes above the control values, which
      were 6.7+/-1.1 and 3.3+/-0.6 nmol min(-1) mg(-1) protein for 4-BA and 9-AA,
      respectively. On the other hand, the (K)(m)'s, which were similar for both
      aldehydes (about 25 micro M), did not change significantly with any inducer. The
      use of purified rat CYP1A1, 2E1, 2B1 and 2C11 in a reconstituted system showed
      that only 2B1 and 2C11 could oxidize both substrates with a high turnover. 3. In
      human liver microsomes, the oxidation rates of these aldehydes (1.6+/-0.2 and
      0.42+/-0.1 nmol min(-1) mg(-1) protein for 4-BA and 9-AA, respectively) were
      lower than those of rat but with similar K(m)'s(20-26 microm). 4. The oxidation
      of these aldehydes was also determined with cDNA-expressed CYP1A1, 1A2, 2A6, 2B6,
      2C9, 2D6, 2E1 and 3A4 and with a characterized bank of 14 human liver microsomes.
      In a reconstituted system, only CYP2B6, 2A6, 3A4 and with a lower turnover 2C9
      oxidized both substrates. 5. Among the CYP marker activities of the 14 human
      samples, good correlations were only observed between CYP3A-dependent 6 beta
      testosterone hydroxylase and the oxidation of 4-BA (r = 0.74) or 9-AA (r = 0.80)
      and between the oxidation of 4-BA versus 9-AA (r = 0.74). Weak correlations were
      also found between the 2B6-linked S-mephenytoin N- demethylase and the oxidation
      of 4-BA (r = 0.58) or 9-AA (r = 0.65). 6. Inhibition experiments revealed that
      the oxidation of these aldehydes was inhibited by ketoconazole, 8
      methoxypsoralene and sulphophenazole, selective inhibitors for P4503A6, 2A6 and
      2C9, respectively. 7. In summary, based on the use of cDNA-expressed CYPs,
      correlation analysis and chemical inhibition, the metabolism in human liver
      microsomes of these aldehydes appears primarily catalysed by CYP3A, although
      CYP2A6, 2B6 and 2C9 may play a role. 9-AA and particularly 4-BA, owing to the
      high rate of its metabolism, may be two novel useful fluorescent probe substrates
      for assaying CYP activities in various species.

PMID- 12519691
TI  - Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic
      agent mexiletine.
AB  - 1. Mexiletine is extensively metabolized in man by C- and N-oxidation and the aim
      of the present study was to characterize major cytochrome P450 enzyme(s) involved
      in the formation of N-hydroxymexiletine. 2. Incubations with genetically
      engineered microsomes indicated that the formation rate of N-hydroxymexiletine
      was highest in the presence of microsomes expressing high levels of either CYP1A2
      or CYP2E1 and the formation of N-hydroxymexiletine by human liver microsomes was
      inhibited about 40% by antibodies directed against CYP1A1/1A2 or CYP2E1.
      Additional incubations demonstrated that formation of N-hydroxymexiletine was
      decreased 47 and 51% by furafylline, 40 microm and 120 microm, respectively, and
      decreased 55 and 67% by alpha-naphthoflavone, 1 microm and 3 microm, respectively
      (all p < 0.05 versus control). 3. The formation rate of N-hydroxymexiletine in
      human liver microsomes was highly correlated with CYP2B6 (RS-mexiletine, r =
      0.7827; R-(-)-enantiomer, r = 0.7034; S-(+)-enantiomer, r = 0.7495), CYP2E1 (S
      (+)-enantiomer, r = 0.7057) and CYP1A2 (RS-mexiletine, r = 0.5334; S-(+)
      enantiomer, r = 0.6035). 4. In conclusion, we have demonstrated that CYP1A2 is a
      major human cytochrome P450 enzyme involved in the formation of N
      hydroxymexiletine. However, other cytochrome P450 enzymes (CYP2E1 and CYP2B6)
      also appear to play a role in the N-oxidation of this drug.

PMID- 12519692
TI  - Metabolic fate of pitavastatin, a new inhibitor of HMG-CoA reductase: human UDP
      glucuronosyltransferase enzymes involved in lactonization.
AB  - 1. Pitavastatin is a potent competitive inhibitor of HMG-CoA reductase little
      metabolized in hepatic microsomes. Pitavastatin lactone, which can be converted
      back to the unchanged form, is the major metabolite of pitavastatin in humans. To
      clarify the mechanism of the lactonization of pitavastatin and the metabolic
      properties of the lactone, we performed experiments in vitro. 2. On addition of
      UDP-glucuronic acid, human hepatic microsomes produced pitavastatin lactone and
      an unknown metabolite (UM-2). UM-2 was converted to its unchanged form by
      enzymatic hydrolysis and to a lactone form non-enzymatically. Using several human
      UGT-expressing microsomes, UGT1A3 and UGT2B7 were principally responsible for
      glucuronidation of pitavastatin leading to lactonization. 3. No marked difference
      in intrinsic clearance between pitavastatin and its lactone form was detected in
      human hepatic microsomes. 4. Pitavastatin lactone showed no inhibitory effects on
      CYP2C9- and CYP3A4-mediated metabolism of model substrates in contrast to other
      HMG-CoA reductase inhibitors. 5. The mechanism of pitavastatin lactone formation
      has been clarified, in that glucuronidation by UGT occurs first followed by
      lactonization via an elimination reaction. It was also found that pitavastatin
      lactone demonstrates no drug-drug interactions.

PMID- 12519693
TI  - Catalytic activities of cytochrome P450 enzymes and UDP-glucuronosyltransferases
      involved in drug metabolism in rat everted sacs and intestinal microsomes.
AB  - 1. The use of everted sacs of the small intestine as an enzyme source for
      studying the metabolism of xenobiotics by cytochrome P450 (P450, CYP) enzymes and
      UDP-glucuronosyltransferases has been investigated. 2. Most of the drug oxidation
      activities for testosterone, bufuralol, ethoxyresorufin and 7-ethoxycoumarin
      resided in the upper part of the everted sacs and in intestinal microsomes.
      Testosterone 6 beta-hydroxylase activities in the everted sacs were about two
      times higher than those in the intestinal microsomes. By freezing and thawing
      treatment, the testosterone 6 beta- and 16 alpha-hydroxylase activities of the
      everted sacs were considerably decreased, and those of the intestinal microsomes
      were abolished. 3. Microsomal testosterone 6 beta-hydroxylation, bufuralol 1'
      hydroxylation, and pentoxyresorufin and ethoxyresorufin O-dealkylation were
      inhibited by ketoconazole, quinine, metyrapone and alpha-naphthoflavone
      respectively. Immunoreactive proteins using anti-CYP2B1 and anti-CYP3A2
      antibodies were detected in the upper and middle parts of the rat small
      intestine. 4. Except for morphine 3-glucuronidation, glucuronidation activities
      in intestinal microsomes or everted sacs were not dependent on the intestinal
      region. The lower part of the everted sacs exhibited about 10 times higher
      morphine-3-glucuronidation activities compared with those of the upper part. The
      glucuronidation activities of 4-nitrophenol in the everted sacs were 10 times
      higher than those in microsomes. 5. These results demonstrated that the upper
      part of rat small intestine serves as the major site for intestinal P450-mediated
      first-pass metabolism. CYP3A enzymes in rat intestinal microsomes may not be
      stable but probably play an important role in drug oxidations. The high activity
      of glucuronidation in the rat small intestine should also be considered in terms
      of drug metabolism.

PMID- 12519694
TI  - Studies on the inhibition of human cytochromes P450 by selenocysteine Se
      conjugates.
AB  - 1. To investigate whether cytochrome P450 (P450) inhibition can contribute to the
      chemopreventive activity of selenocysteine Se-conjugates (SeCys conjugates), 21
      SeCys conjugates were screened for their inhibitory potency towards seven of the
      most important human P450s. 2. The majority of the SeCys conjugates produced near
      complete inhibition of CYP1A1 at a concentration of 250 microm. The most potent
      inhibitor, Se-benzyl-L-selenocysteine, displayed an IC50 of 12.8 +/- 1.2 microm.
      CYP2C9, -2C19 and -2D6 were moderately (50-60%) inhibited by the SeCys
      conjugates. CYP1A2, -2E1 and -3A4 were least inhibited. 3. Studies on the
      susceptibility of CYP1A1 to SeCys conjugates implicated a thiol-reactive
      intermediate, as evidenced by reduced inhibition levels in the presence of
      glutathione and N-acetyl cysteine. Uncoupling of the P450-catalytic cycle was of
      no importance as ROS scavengers did not influence inhibition levels. 4. P450
      inhibition by two physiologically relevant metabolite classes of SeCys conjugates
      was also studied. N-acetylation of SeCys conjugates consistently increased the
      inhibitory potency towards CYP1A2, -2C19, -2E1 and -3A4. Beta-lyase catalysed
      bioactivation of alkyl-substituted SeCys conjugates or Se-benzyl-L-selenocysteine
      produced little or no additional inhibition of P450 activity. For Se-phenyl-L
      selenocysteine, however, significant increases in P450 inhibition were obtained
      by beta-lyase pre-incubation. 5. It is concluded that the potent and relatively
      selective CYP1A1 inhibition exerted by SeCys conjugates may contribute to their
      chemopreventive activity.

PMID- 12519695
TI  - CYP2A13-catalysed coumarin metabolism: comparison with CYP2A5 and CYP2A6.
AB  - 1. We investigated the total metabolism of coumarin by baculovirus (BV)-expressed
      CYP2A13 and compared it with metabolism by BV-expressed CYP2A6. The major
      coumarin metabolite formed by CYP2A13 was 7-hydroxycoumarin, which accounted for
      43% of the total metabolism. The product of 3,4-epoxidation, o
      hydroxyphenylacetaldehyde (o-HPA), accounted for 30% of the total metabolites. 2.
      The K(m) and V(max) for CYP2A13-mediated coumarin 7-hydroxylation were 0.48+/
      0.07 micro m and 0.15+/-0.006 nmol min(-1) nmol(-1) CYP, respectively. The V(max)
      of coumarin 7-hydroxylation by CYP2A13 was about 16-fold lower than that of
      CYP2A6, whereas the K(m) was 10-fold lower. 3. In the mouse, there were two
      orthologues for CYP2A6: CYP2A4 and CYP2A5, which differed by only 11 amino acids.
      However, CYP2A5 is an efficient coumarin 7-hydroxylase, where as CYP2A4 is not.
      We report here that BV-expressed CYP2A4 metabolizes coumarin by 3,4-epoxidation.
      Two products of the 3,4-epoxidation pathway, o-HPA and o-hydroxyphenylacetic acid
      (o-HPAA), were detected by radioflow HPLC. 4. The K(m) and V(max) for the
      coumarin 3,4-epoxidation by CYP2A4 were 8.7+/-3.6 micro m and 0.20+/-0.04 nmol
      min(-1) nmol(-1) CYP, respectively. Coumarin 7-hydroxylation by CYP2A5 was more
      than 200 times more efficient than 3,4 epoxidation by CYP2A4.

PMID- 12519696
TI  - Sulphoxidation of ethyl methyl sulphide, 4-chlorophenyl methyl sulphide and
      diphenyl sulphide by purified pig liver flavin-containing monooxygenase.
AB  - 1. The biotransformation of ethyl methyl sulphide (EMS), 4-chlorophenyl methyl
      sulphide (CPMS) and diphenyl sulphide (DPS) to their corresponding sulphoxides by
      purified flavin-containing monooxygenase (FMO) is described. 2. Purified pig
      liver flavin-containing monooxygenase catalysed the sulphoxidation of EMS, CPMS
      and DPS to their corresponding sulphoxides and the reactions followed single
      enzyme Michelis-Menten kinetics. 3. The apparent K(m) and V(max) for the
      sulphoxidation of EMS were 1.38+/-0.05 mM and 78.74+/-3.9 nmoles mg(-1) protein
      min(-1), respectively. The apparent K(m) and V(max) for the sulphoxidation of
      CPMS were 0.185+/-0.03 mM and 103+/-5.0 nmoles mg(-1) protein min(-1),
      respectively. The apparent K(m) and V(max) for the sulphoxidation of DPS were
      0.068+/-0.002 mM and 49.26+/-2.05 nmoles mg(-1) protein min(-1), respectively. 4.
      A significant reduction of the sulphoxidation of these simple sulphides was
      observed with addition of 1-naphthylthiourea in the incubation medium. On the
      other hand, incorporation of catalase and superoxide dismutase into the
      incubation media produced no appreciable inhibition of the observed
      sulphoxidation of the sulphides. 5. These results suggest that FMO is
      responsible, at least in part, for the sulphoxidation of nucleophilic sulphides
      as well as for the oxidation of sulphur atoms that reside within or adjacent to
      aromatic systems.

PMID- 12519697
TI  - Oxidative activation of acylguanidine prodrugs: intestinal presystemic activation
      in rats limits absorption and can be inhibited by co-administration of
      ketoconazole.
AB  - 1. The disposition of acyl prodrugs was studied to improve the delivery of a
      guanidine-containing parent compound with poor membrane permeability and poor
      absorption. 2. The prodrugs were evaluated in vitro and in vivo for conversion to
      drug. Prodrugs were evaluated for hydrolytic or oxidative bioactivation in
      intestinal homogenate and rat liver S9 or microsomes. The disposition of the
      prodrugs in vivo was monitored in bile duct-cannulated rats. 3. Compounds with n
      alkylacyl groups were efficiently bioactivated, but were hydrolysed before
      absorption. 4. Hydrolytic bioactivation could be blocked in vitro by branching in
      the alkyl chain. These compounds showed modest improvements in absorption,
      despite favourable permeability. Experiments with liver microsomes demonstrated
      efficient NADPH-dependent oxidative bioactivation, which was proposed to occur
      through a CYP-mediated side chain oxidation followed by cyclization and release
      of parent compound. Ketoconazole co-administration yielded approximately a
      twofold increase in absorption. 5. The hydrolytically stable prodrugs were
      successful in increasing absorption of parent drug and were efficiently
      bioactivated, but they did not yield increased systemic levels of drug.

PMID- 12519698
TI  - Preparation of uniform titanium dioxide (TiO2) polystyrene-based composite
      particles using the glass membrane emulsification process with a subsequent
      suspension polymerization.
AB  - Uniform titanium dioxide (TiO(2))-polystyrene-based composite particles were
      prepared using the glass membrane emulsification process followed by a subsequent
      suspension polymerization. The oil phase, consisting of anatase TiO(2) fine
      powder, monomers, methyl laurate as the hydrophobic additive, Disperbyk-180 and
      the poly(styrene-co-2-ethyl hexylacrylate) were emulsified through the membrane
      pores into the aqueous phase containing stabilizers to form a (solid-in-oil)-in
      water (S/O/W) emulsion of monomer droplets. The suspension polymerization was
      carried out at 343 K for 24 h under a nitrogen atmosphere. An SPG membrane with a
      pore size of 5.25 microm was employed and 20-25 microm TiO(2)-polystyrene based
      composite particles were obtained depending on the composition of polymerizing
      oil phase. The effects of the co-monomer, 2-ethylhexyl acrylate and the cross
      linking agent, divinyl benzene on the dispersion stability of TiO(2) in the oil
      phase, the surface feature of the particle and the encapsulation loading were
      investigated in this study. The membrane emulsification process was capable of
      preparing the composite particles with approximately 5 wt% of TiO(2)
      encapsulated, which accounts for with at least 85 wt% of TiO(2) in the oil phase.

PMID- 12519699
TI  - Performance of titanium dioxide microcapsules as a photo-oxidation catalyst for
      decolourization of methylene blue.
AB  - The performance of anatase type titanium dioxide (TiO(2)) encapsulated with
      styrenic copolymers via the solvent evaporation or suspension polymerization
      process was investigated as a photocatalyst for the decolourization of methylene
      blue (MB, 3,4-bis(dimethylamino)-phenothiazine-5-thionium chloride) in the
      aqueous phase. The TiO(2) microcapsules, loaded with 4-8 wt% TiO(2), were
      dispersed in a MB aqueous solution containing an adequate amount of hydroperoxide
      as an oxygen source, and the mixture was exposed to 365 nm UV light. The
      decolourization of MB proceeded according to the first order of the MB
      concentration. The apparent rate constant, defined based on the unit weight of
      loaded TiO(2), depended on the initial concentration of MB. The capsule walls,
      composed of cross-linked and/or uncross-linked poly(styrene-co-2-ethylhexyl
      acrylate), favoured the adsorption of MB on the capsule surface and promoted the
      decomposition. The observations of the cross-section of microcapsules by
      transmission electron microscopy (TEM) showed similar morphology of microcapsules
      regardless of preparation method; a thin layer of hydrophilic TiO(2) particles
      being localized near the particle surface. The sustainability of the
      microcapsules was also proved by doing experiments successively for 7 days.
      Smaller size microcapsules were favoured for the decomposition of MB, and the
      rate constant increased with the surface area of microcapsules in unit volume of
      the reaction mixture. Although large size microcapsules with uncross-linked
      polymer wall had a disadvantage of breaking under high shear agitation, those
      prepared with cross-linked polymer wall by suspension polymerization still
      remained effective after the sustainability test for 7 days.

PMID- 12519701
TI  - Microcapsules from starch granules.
AB  - A preparation of microcapsules from granular potato starch by its prolonged (up
      to 48 h) soaking in water is proposed. The effects of temperature and size of
      granules is studied. Such treatment removes the amorphous part of the granule
      interior, forming empty domains inside granules. Material evacuated from the
      granules was identified as amylopectin together with amylose. The application of
      such pre-treated granules for microencapsulation of various fragrant compounds
      (angelicalactone, diacetyl, dibenzyl ether, 2,6-lutidine and myrcene) from their
      vapours and from their liquid state is described. Depending on pre-treatment of
      starch and the microencapsulation method applied, the amount of trapped guest
      molecules is up to 30 wt%

PMID- 12519700
TI  - Encapsulation of a lipid precursor, the eicosapentaenoic acid, to study the
      development of the Crassostrea gigas oyster flavours.
AB  - The present study is part of a larger project whose aim is to understand how the
      oyster Crassostrea gigas develops its aromas from a lipid precursor, the
      eicosapentaenoic acid (EPA), in glyceride form. The objective of this study is,
      therefore, to prepare an encapsulation process that will enable the bivalve to be
      supplied with this lipid precursor. The complex coacervation method was chosen as
      it gave the best compatible microcapsules with respect to the nutritional aspects
      of oyster (i.e. digestibility) and the environmental constraints (i.e. behaviour
      and stability in seawater). The aim of this study is to manufacture and optimize
      a process of complex coacervation, to obtain capsules made of gelatin and acacia
      gum with a size under 100 microm in diameter and containing very small drops of
      cod liver oil (rich in EPA). The preservation of these microcapsules in seawater
      has been confirmed.

PMID- 12519702
TI  - Viscosity of polymer solution phase and other factors controlling the dissolution
      of theophylline microspheres prepared by the emulsion solvent evaporation method.
AB  - The objectives of this investigation are to evaluate the effect of the viscosity
      of polymer solution phase on microsphere properties, especially the drug release
      characteristics since no studies on this formulation variable have been reported.
      Also, since it is known that polymer molecular weight affects both the viscosity
      of the polymer solution and the release properties of microspheres, the
      interaction of these factors was studied. Microspheres with 33% theoretical drug
      loading of anhydrous theophylline core material were prepared by the emulsion
      solvent evaporation method. Two cellulose acetate butyrate polymers, (CAB381-2,
      CAB381-20), chemically similar but having different molecular weights, were used
      to prepare different polymer solutions having different apparent viscosities in
      acetone. A Brookfield viscometer was used to evaluate the viscosities of polymer
      solutions. Dissolution rates of microspheres prepared from the polymer solutions
      were inversely related to the initial polymer solution viscosities for both
      CAB381-2 and CAB381-20. The times for the release of 30 and 50% of the drug from
      the microspheres have a linear relationship with initial polymer solution
      viscosity. Initial release was significantly decreased with increasing polymer
      solution viscosity. Unlike CAB381-2 microspheres which follow Higuchi spherical
      matrix release kinetics, microspheres prepared from the higher molecular weight
      polymer (CAB381-20) showed extended release dissolution profiles with near zero
      order kinetics. It is evident that both the polymer solution viscosity and the
      molecular weight have an effect on the drug release from microspheres. These
      results suggest that release rates of matrix microspheres could be predictably
      optimized by adjusting the viscosity of polymer solutions.

PMID- 12519703
TI  - Solvent extraction employing a static micromixer: a simple, robust and versatile
      technology for the microencapsulation of proteins.
AB  - The potential of a static micromixer for the production of protein-loaded
      biodegradable polymeric microspheres by a modified solvent extraction process was
      examined. The mixer consists of an array of microchannels and features a simple
      set-up, consumes only very small space, lacks moving parts and offers simple
      control of the microsphere size. Scale-up from lab bench to industrial production
      is easily feasible through parallel installation of a sufficient number of
      micromixers ('number-up'). Poly(lactic-co-glycolic acid) microspheres loaded with
      a model protein, bovine serum albumin (BSA), were prepared. The influence of
      various process and formulation parameters on the characteristics of the
      microspheres was examined with special focus on particle size distribution.
      Microspheres with monomodal size distributions having mean diameters of 5-30
      micro m were produced with excellent reproducibility. Particle size distributions
      were largely unaffected by polymer solution concentration, polymer type and
      nominal BSA load, but depended on the polymer solvent. Moreover, particle mean
      diameters could be varied in a considerable range by modulating the flow rates of
      the mixed fluids. BSA encapsulation efficiencies were mostly in the region of 75
      85% and product yields ranged from 90-100%. Because of its simple set-up and its
      suitability for continuous production, static micromixing is suggested for the
      automated and aseptic production of protein-loaded microspheres.

PMID- 12519704
TI  - A supercritical fluid-based coating technology 1: process considerations.
AB  - A novel solvent-free particle coating process, based on the solvent properties of
      supercritical fluids (SCF) is described. It consists of dissolving one or more
      coating materials in supercritical CO(2) and then adjusting T/P conditions in the
      autoclave so that the coating material becomes insoluble in the CO(2). This
      insolubilization step causes a coating to deposit on the surface of suspended
      particles. This process has been applied to bovine serum albumin and sugar
      granules. Coating was effective, but different morphologies were obtained
      depending on the coating material used. A discontinuous coating has been made
      using trimyristin, since this material precipitates as micro-needles. Conversely,
      a smooth, regular coating has been obtained with a commercially available mixture
      of glycerides and glyceride esters of PEG (Gelucire 50/02) acting like a film
      forming agent.

PMID- 12519705
TI  - A supercritical fluid-based coating technology. 2: solubility considerations.
AB  - Solubility measurements of candidate coating materials have been performed in
      supercritical (SC) CO(2) so as to select appropriate coating materials for
      implementation of a solvent-free coating process previously described. Solubility
      of lipidic compounds such as waxes (paraffin, beeswax, Carnauba wax), pure
      triglycerides (tricaprin, trimyristin, tripalmitin, tristearin) and mixture of
      glycerides and fatty acid esters (Gelucire) in SC CO(2) were evaluated in a
      static mode under different temperature and pressure conditions, ranging from 13
      52 degrees C and from 50-220 bar, whether the CO(2)was in its liquid or SC state.
      It was shown that the compounds which are mixtures of various components give
      rise to a selective extraction of the lower melting point components, as
      evidenced from thermal analysis of soluble and insoluble fractions of the coating
      materials.

PMID- 12519706
TI  - A supercritical fluid-based coating technology. 3: preparation and
      characterization of bovine serum albumin particles coated with lipids.
AB  - Solvent-free microparticles, loaded with bovine serum albumin as a model protein,
      were produced using a novel supercritical (SC) fluid-based coating technology.
      Coating material consists either of trimyristin (Dynasan 114) or of Gelucire 50
      02. Microparticles obtained were characterized as regards their morphology,
      protein content and in vitro release profile. A discontinuous coating made of
      micro-needles of trimyristin led to an initial burst release of approximately 70%
      in 30 min. However, a prolonged release of the BSA could be achieved in a
      phosphate buffer solution at 37 degrees C over a 24 h period from particles
      coated with Gelucire 50-02. Furthermore, it was shown that BSA does not undergo
      any degradation after SC CO(2) treatment under the conditions used in the coating
      process.

PMID- 12519707
TI  - Anaesthesiological experiences with whole body hyperthermia.
AB  - OBJECTIVE: In order to investigate the safety of whole body hyperthermia (WBH)
      within the context of systemic Cancer Multistep Therapy (sCMT) in patients with
      disseminated malignancies, cardiopulmonary changes and various organ functions
      were examined. METHODS AND PROCEDURES: Fifty-seven sCMT treatments were performed
      in 22 patients. WBH with a plateau phase of 1 h at 41.8 degrees C was induced by
      an IRATHERM 2000 device. Cardiopulmonary parameters were measured at 37, 40, 41.8
      and 39 degrees C by use of a pulmonary artery catheter, femoral oxymetry and a
      radial artery catheter. Organ functions of the liver, kidney, cardiovascular and
      central nervous system were evaluated before and after treatment. RESULTS:
      Compared with the initial values, significant alterations were found of most
      cardiopulmonary parameters in the sense of hypercirculation at 41.8 degrees C.
      With the exception of extra vascular lung water index, all parameters showed a
      clear tendency towards the pre-treatment levels at 39 degrees C. In eight out of
      57 sCMT treatments, reversible organ dysfunctions were observed. Comparison of
      radial and femoral arterial blood pressure showed significantly different values
      at 40 and 41.8 degrees C. CONCLUSIONS: WBH induces cardiovascular stress, but by
      careful selection of patients and appropriate anaesthesiological monitoring it
      can be performed safely using general anaesthesia. This enables further
      evaluation of WBH in multimodal treatment concepts.

PMID- 12519708
TI  - Clinical pilot studies on pre-operative hyperthermic tumour ablation for advanced
      breast carcinoma using an 8 MHz radiofrequency heating device.
AB  - The multimodality treatment approach for advanced breast cancer provides survival
      advantages with decreased locoregional and distant recurrences, but these
      intensive anti-tumour treatments cause severe myelosuppression. Thus, in this
      study, the usefulness of pre-operative anti-tumour treatment without
      myelosuppression was investigated. Nine patients with advanced breast carcinoma
      underwent pre-operative hyperthermic tumour ablation (HTA) using an 8 MHz
      radiofrequency (RF) heating device (Thermotron RF-8) combined with a grounded
      needle electrode. The patients had a mean age of 58.3+/-13.9 years and included
      four patients with stage IIIA, two with stage IIIB and three with stage IV
      cancer. The target temperature was over 50 degrees C. They tolerated pre
      operative HTA therapy well with no early or late complications. The initial mean
      tumour size was 122.1+/-71.5 cm3 and the post-HTA tumour size was 82.2+/-63.4
      cm3; the reduction rate was significant (p = 0.000 293). After the pre-operative
      HTA, all patients underwent surgery with Level III nodal extirpation. Post
      operatively, no locoregional recurrence was observed. Microscopic examination of
      the primary focus showed complete coagulation necrosis expanding for a diameter
      of 3.5-5.0 cm. Taken together, the pre-operative HTA was a safe, well-tolerated
      and effective treatment, achieving tumour reduction as well as complete
      coagulation necrosis that resulted in a large volume of destruction in breast
      cancer tissue.

PMID- 12519709
TI  - Hepatic clearance of arterially infused ferromagnetic particles.
AB  - OBJECTIVE: Arterial embolization hyperthermia (AEH) consists of arterially
      embolizing tumours with ferromagnetic particles that generate hysteretic heating
      on exposure to an alternating magnetic field. It was the objective of this study
      to determine if such particles are cleared from the liver. METHOD: A lobe of
      normal liver in three pigs was arterially embolized with 300 mg of gamma-Fe2O3
      particles (150 nm) suspended in lipiodol. The same liver lobe of three other pigs
      was embolized with 300 mg of ferromagnetic polymer matrix-encapsulated
      microspheres (32 microm) suspended in 1% tween-water. Samples of liver and blood
      were obtained before infusion, and at 60 min and 28 days after arterial infusion.
      At 28 days, samples of lung and other abdominal viscera were also obtained. The
      tissue samples were chemically analysed for iron content, and submitted to
      histopathological examination. RESULTS: There was no significant reduction in the
      hepatic iron concentration in either treatment group 28 days after infusion. Both
      types of particles illicited an immunogenic response and were extensively
      phagocytosed in the liver. The particle/lipiodol suspension caused extensive
      necrosis of liver, while the microsphere/tween-water suspension was well
      tolerated. Small amounts of both types of ferromagnetic particles embolized in
      the lungs, but there was no evidence of embolization into other organs. There
      were no haematological or biochemical changes and all subjects experienced
      uneventful 28-day survivals. CONCLUSION: This study has shown that, although
      arterially infused ferromagnetic particles were extensively phagocytosed, there
      was no significant hepatic clearance 28 days after infusion. It also determined
      that the suspension of 150 nm ferromagnetic particles in lipiodol was too vaso
      occlusive for use in hepatic tissue. However, the suspension of 32 microm
      microspheres containing ferromagnetic particles in tween-water was safe and well
      tolerated.

PMID- 12519710
TI  - Effect of nitric oxide on mortality of mice after whole body hyperthermia.
AB  - The objective of this study is to find the role of nitric oxide (NO) in the
      haemodynamics of mice subjected to heat stress caused by Whole Body Hyperthermia
      (WBH) treatment. L-arginine (L-arg), a natural substrate for NO synthase (NOS), N
      nitro-L-arginine methyl ester (L-NAME), a preferential inhibitor of endothelial
      NOS, and dexamethasone, a preferential inhibitor of inducible NOS, have been used
      to study the role of NO in thermal injury caused by WBH treatment. Nitrite in
      plasma and mortality of Swiss male mice subjected to WBH treatment induced by
      radiant heat (40 degrees C fo 1 h at 50-55% relative humidity), were monitored in
      mice pre-treated with either L-NAME, dexamethasone or L-arg. A batch of mice
      subjected to 24 h fasting prior to WBH treatment was also used to study the above
      parameters. Injections with 1.5 mg/kg or above of L-NAME just before WBH
      treatment, induced mortality in mice, with a corresponding drop in plasma nitrite
      values. L-arg (8 mg/kg) pre-treatment reversed the killing caused by L-NAME in
      WBH treated mice. L-arg (60 mg/kg) pre-treatment induced mortality in mice
      subjected to WBH treatment. In the fasted group, a very low dose of L-arg (8
      mg/kg) given before WBH treatment led to a significant increase in plasma nitrite
      levels. In both the normal and fasted groups of mice, 120 mg/kg of L-arg pre
      treatment resulted in a sharp increase in plasma nitrite values and subsequent
      death of mice. The results throw up an important finding, in that the interaction
      of elevated body temperature, with either a decrease or over production of
      nitrite oxide, leads to modulation of thermal injury of mice, caused by WBH
      treatment.

PMID- 12519711
TI  - Effects of hyperthermia on the rat bladder: a pre-clinical study on thermometry
      and functional damage after treatment.
AB  - The rat bladder was heated using a microwave applicator which was equipped with a
      system of circulating deionized water. The applicator was operated at 434 MHz and
      was placed at the ventral side with the rats in supine position. Temperatures in
      the bladder and adjacent were monitored using thermocouples with single or
      multiple sensors. One thermocouple located most centrally in the bladder served
      as reference. The rats were treated at intravesical reference temperature of 41,
      42, 43, 44 and 45 degrees C for 1 h. The heating time to reach the reference
      temperature was approximately 5 min. Temperatures inside the bladder varied
      within 0.5 degrees C from the reference value, while the temperatures in the
      urethra were approximately 1.0 degrees C lower. At the left and the right side of
      the outer bladder wall, temperatures were approximately 0.5 degrees C lower than
      the reference value, while the temperature on the dorsal and ventral sides of the
      bladder wall were 1.0-1.5 degrees C lower. In the rectum, located in the
      treatment field, the temperature reached 39.1, 40.5, 42.4 and 42.5 degrees C
      after 1 h of hyperthermia at intravesical reference temperatures of 41, 42, 43,
      44 and 45 degrees C, respectively. Body core temperature measured in the
      esophagus behind the pericardium never exceeded 40.0 degrees C. The capacity of
      the bladder was assessed after 1 h at 43, 44 and 45 degrees C at various
      intervals after heat treatment. In the sham treated control group and in the
      animals treated at 43 degrees C, no reduction in bladder capacity was observed.
      The treatment group where the bladder was kept at 44 degrees C for 1 h showed a
      clear reduction in bladder capacity at days 1 and 3 after hyperthermia. In the 45
      degrees C treatment group, four out of seven rats died, this within a few days
      after treatment. The three surviving rats were tested for bladder capacity and
      all had a reduced capacity at days 3 and 7 post-treatment. Four weeks after 44
      degrees C hyperthermia, all rats had recovered. After hyperthermia, depending on
      the heat-dose, an increase in blood urea nitrogen (BUN) was observed. After
      treatment at 42, 43 and 44 degrees C, peak values were observed after
      approximately 1 day (16 or 24 h) followed by recovery; after 42 degrees C, BUN
      levels were almost back to normal after 1 week; after 43 degrees C, the level was
      still twice as high as control levels; and after 44 degrees C, recovery of BUN
      levels to normal seemed slow, 1 week after treatment it was still five times as
      high as control. From these results, it is concluded that temperatures in the
      bladder below 44 degrees C are well tolerated. After 1 h at 44 degrees C, a
      transient decrease in bladder capacity was observed, as well as a high level of
      azotemia. After 1 h at 45 degrees C, a high mortality rate was observed. These
      observations agree with early clinical observations and may be used as guidelines
      for further clinical work.

PMID- 12519712
TI  - Treatment planning for capacitive regional hyperthermia.
AB  - Capacitively coupled hyperthermia devices are widely in use, mainly in Asian
      countries. In this paper, a comprehensive treatment planning system, including a
      Specific Absorption Rate (SAR) and thermal model for capacitively coupled
      hyperthermia, is described and demonstrated using a heterogeneous patient model.
      In order to accurately model a hyperthermia treatment, simulation at high
      resolution is mandatory. Using the quasi-static approximation, the
      electromagnetic problem can be solved at high resolution with acceptable
      computational effort. The validity of the quasi-static approximation is
      demonstrated by comparing the Maxwell solution of a phantom problem to the quasi
      static approximation. Modelling of capacitive hyperthermia of the prostate
      reveals the difficulty of heating deep-seated tumours in the pelvic area.
      Comparison of the SAR distribution in the heterogeneous patient model and a
      patient shaped agar phantom shows a shielding effect of the pelvic bone and the
      influence of the fat-muscle distribution. It is shown that evaluation of
      capacitive hyperthermia with agar phantoms leads to overly optimistic
      conclusions. Therapeutic relevant tumour temperatures can only be obtained by
      permitting temperature extrema in normal tissue. This concurs with clinical
      practice, where treatment-limiting hot spots restrict the tumour temperature. It
      is demonstrated that the use of very cold overlay bolus bags has only a very
      superficial effect. The presented model can be used for individual treatment
      planning and optimization, for the evaluation of capacitive applicator
      modifications and comparison with other devices.

PMID- 12519713
TI  - Stability and accuracy of power and phase measurements of a VVM system designed
      for online quality control of the BSD-2000 (-3D) DHT system.
AB  - Accurate control of power and phase is essential for the quality assurance of
      hyperthermia treatments. Hereto, an external measurement device was inserted,
      built around a Vector Voltmeter (VVM), in order to assess online the performance
      of the steering capability of the BSD-2000 and later the BSD-2000-3D system. This
      paper only concerns the power and phase calibration of the signal in the path
      between the power and phase detection probes of the BSD-system and power and
      phase measurement point of the VVM. The calibration is performed in the frequency
      range of 60-120 MHz using a network analyser with a frequency range of 0.01-500
      MHz. More importantly, by repeating the calibration periodically over the last 3
      years, the stability and accuracy of the power and phase measurements were
      determined using the VVM system. The results of the power calibration show that
      the VVM system, concerning its power and phase measurement, is stable in time.
      The variation of the power measured with the VVM system is less than 0.22 dB
      (5.2%) for the latest configuration of the BSD-2000-3D system. The variation of
      the VVM-based phase measurements of the latter configurations is 1.1 degrees or
      less. From the results of the power and phase measurements in the BSD 2000 system
      reported in previous studies using other measurement systems, it follows that the
      uncertainties of the power and phase measurements with the currently proposed VVM
      system are small enough to assess accurately the performance of the BSD system
      concerning its steering capability.

PMID- 12519714
TI  - Phantom and animal tissues for modelling the electrical properties of human
      liver.
AB  - The dielectric properties of human liver were characterized over the frequency
      range of 0.3-3 GHz for freshly excised tissue samples of primary hepatocellular
      carcinoma, metastatic colorectal carcinoma, and normal liver tissues resected
      from the tumour margin. On average, the dielectric constant (epsilon(r)) of
      freshly excised human liver tumour was 12% higher than that of surrounding normal
      liver, and the electrical conductivity (sigma) of tumour was 24% higher. In order
      to establish suitable tissue models for human liver, the electrical properties
      were compared to measurements of homogenous phantom mixtures, in vitro bovine
      liver, and in vivo canine and porcine liver tissues. The data demonstrate that
      there are several animal tissues that can be used to model the average dielectric
      properties of human liver reasonably accurately, and use of the most readily
      available bovine liver appears well-justified, even when stored for up to 10 days
      in a refrigerator. Additionally, the dielectric properties of in vitro liver
      remained stable over a large temperature range, with sigma rising only 1.1%/
      degrees C in porcine liver (15-37 degrees C) and 2.0%/ degrees C in bovine liver
      (10-90 degrees C), and epsilon(r) decreasing < or =0.2%/ degrees C in both
      tissues. This effort identifies homogeneous solid and liquid phantom models and
      several heterogeneous in vitro tissues that adequately model the dielectric
      properties of human liver tumours for use in quantitative studies of microwave
      power deposition in liver.

PMID- 12519716
TI  - Effect of cooking on the formation of N-nitrosodimethylamine in Korean dried
      seafood products.
AB  - Only N-nitrosodimethylamine (NDMA) was detected when N-nitrosamines (NA) were
      analysed in seven dried seafood products, either uncooked or cooked. The cooking
      methods used were a briquet fire, a gas range, an electric oven, a microwave
      oven, a steam cooker and an electric coil cooker. The contents of NDMA ranged
      from 1.0 to 46.9 microgram kg(-1) in uncooked products. When these samples were
      cooked, regardless of the cooking method, the content of NDMA tended to increase,
      ranging from 1.1 to 630.5 microgram kg(-1). In general, indirect heating such as
      a steam cooker and a microwave oven, as compared with direct heating such as a
      gas range and a briquet fire, caused less increase in NDMA during cooking.

PMID- 12519715
TI  - Effects of caffeine on human health.
AB  - Caffeine is probably the most frequently ingested pharmacologically active
      substance in the world. It is found in common beverages (coffee, tea, soft
      drinks), in products containing cocoa or chocolate, and in medications. Because
      of its wide consumption at different levels by most segments of the population,
      the public and the scientific community have expressed interest in the potential
      for caffeine to produce adverse effects on human health. The possibility that
      caffeine ingestion adversely affects human health was investigated based on
      reviews of (primarily) published human studies obtained through a comprehensive
      literature search. Based on the data reviewed, it is concluded that for the
      healthy adult population, moderate daily caffeine intake at a dose level up to
      400 mg day(-1) (equivalent to 6 mg kg(-1) body weight day(-1) in a 65-kg person)
      is not associated with adverse effects such as general toxicity, cardiovascular
      effects, effects on bone status and calcium balance (with consumption of adequate
      calcium), changes in adult behaviour, increased incidence of cancer and effects
      on male fertility. The data also show that reproductive-aged women and children
      are 'at risk' subgroups who may require specific advice on moderating their
      caffeine intake. Based on available evidence, it is suggested that reproductive
      aged women should consume </=300 mg caffeine per day (equivalent to 4.6 mg kg(-1)
      bw day(-1) for a 65-kg person) while children should consume </=2.5 mg kg(-1) bw
      day(-1).

PMID- 12519717
TI  - Total mercury and methylmercury levels in some New Zealand commercial marine fish
      species.
AB  - Two groups of samples spanning 16 years are reported for methylmercury and total
      mercury. All the samples had been taken from commercial catches and represent 33
      different commercially important New Zealand marine fish species. Results show
      the New Zealand fish species sampled have mean contents of total mercury that
      range between 0.02 and 2.48 mg kg(-1) and mean contents of methylmercury that
      range from less than 0.04 to 1.97 mg kg(-1).

PMID- 12519718
TI  - Determination of several elements in duplicate meals from catering establishments
      using closed vessel microwave digestion with inductively coupled plasma mass
      spectrometry detection: estimation of daily dietary intake.
AB  - An estimation of the dietary exposure of French consumers to 21 essential and non
      essential mineral elements using duplicate meals (breakfast and lunch) purchased
      from catering establishments was investigated after digestion by a closed vessel
      microwave procedure and quantification by ICP-MS. Daily dietary exposure
      estimates for metals and minerals were compared with the Provisional Tolerable
      Weekly Intakes (PTWI), the Tolerable Daily Intake (TDI) or the Acceptable Daily
      Intakes (ADI), as established by the FAO/WHO to estimate the risk of toxicity,
      and the US Recommended Daily Allowances (US RDA) or the Estimate Safe & Adequate
      Daily Dietary Intakes (ESADDI). Moreover, comparisons were made with those from
      previous French studies as well as those from other countries. The estimated mean
      daily intakes were 11 microgram for lithium, 3.42 g for sodium, 192 mg for
      magnesium, 2.03 mg for aluminium, 3.64 g for potassium, 642 mg for calcium, 154
      microgram for chromium, 12.3 mg for iron, 2.15 mg for manganese, 4 microgram for
      cobalt, 74 microgram for nickel, 925 microgram for copper, 10.2 mg for zinc, 147
      microgram for arsenic, 66 microgram for selenium, 112 microgram for molybdenum,
      3.6 microgram for cadmium, 2.32 mg for tin, 3 microgram for antimony, 9 microgram
      for mercury and 34 microgram for lead. For the non-essential (toxic) elements,
      aluminium, tin, antimony, cadmium, arsenic, mercury and lead, the daily intake
      estimates were far below tolerable limits; and similar or somewhat lower than
      their respective PTWI, ADI, TDI, ESADDI and US RDA for individual minerals and
      essential trace elements, with good agreement with other country studies. The
      performance of the multi-elemental ICP-MS technique was also evaluated.

PMID- 12519719
TI  - Pesticide content of infant formulae and weaning foods available in New Zealand.
AB  - A survey of the pesticide content of 25 commercially available infant formulae
      and 30 weaning foods available in New Zealand was undertaken in 1996. It included
      a representative mixture of imported and New Zealand manufactured infant foods.
      Three different pesticide screening techniques were used: a high-sensitivity
      organochlorine screen was carried out on all infant formulae, while a
      multiresidue screen (organochlorine and organophosphorus pesticides, synthetic
      pyrethroids, carbamate pesticides, fungicides and herbicides), and a specific
      screen for dithiocarbamate fungicides were both carried out on all weaning foods
      and on soy-based infant formulae. All results are expressed on a ready-to-feed
      basis. Extremely low levels of residues of three organochlorine compounds (p,p'
      DDE, p,p'-DDT and dieldrin) were detected in infant formulae samples. Residues of
      p,p'-DDE were found in seven of 20 milk-based infant formulae at concentrations
      ranging from 0.03 to 0.5 microgram kg(-1). Residues of p,p'-DDT were found in one
      imported milk-based infant formula at 0.7 microgram kg(-1), and dieldrin residues
      were detected in four of five soy-based infant formulae at concentrations ranging
      from 0.05 to 0.08 microgram kg(-1). The multiresidue pesticide screen detected
      low levels of residues of two organophosphorus pesticides; azinphos-methyl in one
      soy-based infant formula at a level of 22 microgram kg(-1) and pirimiphos-methyl
      in two cereal-based weaning foods at concentrations of 5 and 14 microgram kg(-1).
      None of the other approximately 140 pesticides (including fungicides and
      herbicides) included in the multiresidue screen were detected in any weaning
      foods or soy-based infant formulae, at a detection limit of 10 microgram kg(-1).
      No residues of dithiocarbamate fungicides were detected in any product analysed,
      at a detection limit of 100 microgram kg(-1).

PMID- 12519721
TI  - Occurrence of aflatoxins M(1) and M(2) in milk commercialized in Ribeirao Preto
      SP, Brazil.
AB  - Aflatoxins are toxic metabolites found in foods and feeds. When ruminants eat
      foodstuffs containing aflatoxins B(1) and B(2), these toxins are metabolized and
      excreted as aflatoxin M(1) and M(2) in milk. The aim was to determine the
      incidence of these aflatoxins in commercial milk collected from supermarkets in
      Ribeirao Preto-SP, Brazil, and consisting of 60 ultrahigh temperature (UHT) milk
      samples and 79 pasteurized milk samples. The milk samples were analysed according
      to method 986.16 of AOAC International. None of the milk samples analysed were
      contaminated with aflatoxin M(2), and aflatoxin M(1) was detected in 29 (20.9%)
      of samples in the range 50-240 ng l(-1). The results show that despite a high
      occurrence of aflatoxin M(1) in commercial pasteurized and UHT milk sold in
      Ribeirao Preto in 1999 and 2000, the contamination level of these toxins could
      not be considered a serious public health problem according to MERCOSUR Technical
      Regulations. However, levels in 20.9% of the milk samples exceeded the
      concentration of 50 ng l(-1) permitted by the European Union. Although it is not
      necessary to continue monitoring the incidence and levels of aflatoxins M(1) and
      M(2) in milk samples, surveillance could be appropriate.

PMID- 12519720
TI  - Comparison of dioxin and PCB concentrations in human breast milk samples from
      Hong Kong and the Netherlands.
AB  - The adverse effects of dioxins and polychlorinated biphenyls (PCBs) on human
      health are of increasing concern. These lipophilic compounds are concentrated
      through the food chain and are present in human milk. This study compares PCB
      levels in human milk samples from Hong Kong and Dutch mothers. Ten breast milk
      samples from Hong Kong and 10 from the Netherlands were collected during home
      visits between 2 and 6 weeks postpartum. Total toxic equivalence (TEQ) of dioxin
      and PCBs were determined using the DR-CALUX(R) bioassay. The total dioxin and PCB
      levels in breast milk samples for Hong Kong ranged from 3.1 to 29.9 pg TEQ g(-1)
      lipid and for the Netherlands from 8.9 to 89.5 pg TEQ g(-1) lipid. Despite Hong
      Kong's high degree of industrialization, the levels of dioxin and PCBs were
      fourfold lower in the Hong Kong than in the Dutch samples. This may be due to a
      lower dietary intake of dioxins and PCBs in Hong Kong because of lower background
      levels of these contaminants or to different food habits.

PMID- 12519722
TI  - Ochratoxin A concentrations in Greek domestic wines and dried vine fruits.
AB  - A survey for the presence of ochratoxin A (OTA) was conducted from 1995 to 1999
      on 268 locally produced commercial wines, and on 81 samples of domestic dried
      vine fruits (currants and sultanas) collected between 1998 and 2000 from sites of
      primary storage and processing. The OTA concentration in red dry wines (n = 104,
      median = 0.09 microgram l(-1)) was not significantly different from that for
      white (n = 118, median = 0.06 microgram l(-1)) and rose (n = 20, median = 0.08
      microgram l(-1)) wines. Eighteen samples of dessert wines (sweet, semi-sweet,
      semi-dry) and eight samples of retsina wine showed larger OTA concentrations with
      medians of 0.33 and 0.27 microgram l(-1), respectively. Our data indicate that
      the geographic region of origin influences OTA contamination for the red dry
      wines. In fact, a trend of increasing OTA contamination was observed for red
      wines from northern to southern Greece. Regarding the OTA levels in dried vine
      fruits, sultanas (n = 27, median = 0.6 microgram kg(-1)) were less contaminated
      than currants (n = 54, median = 1.3 microgram kg(-1)). Also, sultanas produced in
      2000 and currants produced in 1999 showed the lowest incidence of OTA
      contamination, with medians of 0.3 and 0.9 microgram kg(-1), respectively.

PMID- 12519723
TI  - Influence of flavour absorption by food-packaging materials (low-density
      polyethylene, polycarbonate and polyethylene terephthalate) on taste perception
      of a model solution and orange juice.
AB  - The influence of flavour absorption by low-density polyethylene (LDPE),
      polycarbonate (PC) and polyethylene terephthalate (PET) on taste perception of a
      model solution containing seven flavour compounds and orange juice in glass
      bottles was studied with and without pieces of the respective plastic films after
      dark storage at 20 degrees C. Owing to absorption, the amount of flavour
      compounds in the model solution exposed to LDPE decreased substantially. From the
      model flavour solution valencene was almost completely absorbed by LDPE, followed
      to a lesser extent by decanal, hexyl acetate, octanal and nonanone. Less flavour
      compounds were absorbed from the model solution by PC and PET. In contrast to
      LDPE, valencene was absorbed in the lowest amounts and decanal in the highest.
      Limonene was readily absorbed from orange juice by LDPE, while myrcene,
      valencene, pinene and decanal were absorbed in smaller quantities. Only three
      flavour compounds were absorbed from orange juice by PC and PET in very small
      amounts: limonene, myrcene and decanal. Although the flavour content between
      controls and polymer-treated samples differed substantially, the loss of flavour
      compounds due to absorption by LDPE, PC and PET did not influence taste
      perception of a model solution and orange juice significantly up to 29 days of
      dark storage at 20 degrees C as determined by triangular taste panel tests.

PMID- 12519724
TI  - Alkylphenol and bisphenol A levels in rubber products.
AB  - Levels of p-t-butylphenol (PTBP), p-t-octylphenol (PTOP), p-nonylphenol (NP) and
      bisphenol A (BPA) in rubber products in food-contact use, infant-related use and
      other uses are reported. Of 60 rubber products tested, PTOP was found in three in
      a concentration range of 2.2-37 microgram g(-1), and NP in 15 in a concentration
      range of 2.6-513 microgram g(-1). PTBP and BPA were not found in any sample. PTOP
      and NP were not detected in any infant-related sample, regardless of the material
      type. In contrast, among the samples with food contact and with other uses, the
      percentages containing PTOP or NP were 33 and 43%, respectively. A migration test
      was performed on eight samples containing NP and used in food-contact
      environments. The migration level of NP from spatulas to n-heptane was 0.83-1.52
      microgram ml(-1). The average migration rates to water, 20% ethanol and n-heptane
      were 0.03, 0.7 and 6.6%, respectively.

PMID- 12519725
TI  - BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts.
AB  - The proapoptotic activity of BID seems to solely depend upon its cleavage to
      truncated tBID. Here we demonstrate that expression of a caspase-8 non-cleavable
      (nc) BID-D59A mutant or expression of wild type (wt) BID induces apoptosis in Bid
      -/-, caspase-8 -/-, and wt primary MEFs. Western blot analysis indicated that no
      cleavage products appeared in cells expressing ncBID. ncBID was as effective as
      wtBID in inducing cytochrome c release, caspase activation, and apoptosis. ncBID
      and wtBID (nc/wtBID) were much less effective than tBID in localizing to
      mitochondria and in inducing cytochrome c release, but only slightly less
      effective in inducing apoptosis. Studies with Apaf-1- and caspase-9-deficient
      primary MEFs indicated that both proteins were essential for nc/wtBID and for
      tBID-induced apoptosis. Most importantly, expression of non-apoptotic levels of
      either ncBID or wtBID in Bid -/- MEFs induced a similar and significant
      enhancement in apoptosis in response to a variety of death signals, which was
      accompanied by enhanced localization of BID to mitochondria and cytochrome c
      release. Thus, these results implicate full-length BID as an active player in the
      mitochondria during apoptosis.

PMID- 12519726
TI  - An iron-dependent bacterial phospholipase D reminiscent of purple acid
      phosphatases.
AB  - Recombinant phospholipase D (PLD) from Streptomyces chromofuscus (scPLD) has been
      characterized using colorimetric assays, spectroscopic investigations, and site
      directed mutagenesis. scPLD, which shows phosphodiesterase activity toward a wide
      variety of phospholipids and phosphatase activity toward p-nitrophenyl phosphate,
      exhibits a visible absorption band with lambda(max) at 570 nm. Metal ion analysis
      performed by inductively coupled plasma mass spectroscopy shows the presence of
      approximately 1 equivalent of iron, 0.27 equivalent of manganese, and 0.1
      equivalent of zinc per mole of protein as isolated. The metal ion content coupled
      with the visible absorption feature is compatible with the presence of Fe(3+)
      tyrosinate coordination. When scPLD was dialyzed against solutions containing
      Mn(2+), Zn(2+) or EDTA, the Fe(3+) content was reduced to variable extents, and
      the residual specific activity correlated well with the residual iron content.
      Sequence homology with metal ion binding motifs in known alkaline phosphatases
      and purple acid phosphatase from red kidney bean shows that most of the residues
      involved in metal ion coordination are conserved among all the sequences
      considered. Mutation of some of these conserved residues (C123A, D151A, Y154F,
      and H391A) produced enzymes lacking iron with dramatically reduced PLD activity
      but little change in secondary structure or ability to bind to small unilamellar
      vesicles of phosphatidylcholine (with Ba(2+)) or phosphatidic acid. We suggest
      that scPLD is a member of a family of phosphodiesterase/phosphatases with
      structural and mechanistic similarity to iron-dependent purple acid phosphatases.

PMID- 12519727
TI  - Pneumonitis and emphysema in sp-C gene targeted mice.
AB  - SP-C-deficient (SP-C -/-) mice developed a severe pulmonary disorder associated
      with emphysema, monocytic infiltrates, epithelial cell dysplasia, and atypical
      accumulations of intracellular lipids in type II epithelial cells and alveolar
      macrophages. Whereas alveolar and tissue surfactant phospholipid pools were
      increased, levels of other surfactant proteins were not altered (SP-B) or were
      modestly increased (SP-A and SP-D). Analysis of pressure-volume curves and forced
      oscillatory dynamics demonstrated abnormal respiratory mechanics typical of
      emphysema. Lung disease was progressive, causing weight loss and cardiomegaly.
      Extensive alveolar remodeling was accompanied by type II cell hyperplasia,
      obliteration of pulmonary capillaries, and widespread expression of alpha-smooth
      muscle actin, indicating myofibroblast transformation in the lung parenchyma.
      Dysplastic epithelial cells lining conducting airways stained intensely for the
      mucin, MUC5A/C. Tissue concentrations of proinflammatory cytokines were not
      substantially altered in the SP-C (-/-) mice. Production of matrix
      metalloproteinases (MMP-2 and MMP-9) was increased in alveolar macrophages from
      SP-C (-/-) mice. Absence of SP-C caused a severe progressive pulmonary disorder
      with histologic features consistent with interstitial pneumonitis.

PMID- 12519728
TI  - Transmembrane nitration of hydrophobic tyrosyl peptides. Localization,
      characterization, mechanism of nitration, and biological implications.
AB  - We have shown previously that peroxynitrite-induced nitration of a hydrophobic
      tyrosyl probe is greater than that of tyrosine in the aqueous phase (Zhang, H.,
      Joseph, J., Feix, J., Hogg, N., and Kalyanaraman, B. (2001) Biochemistry 40, 7675
      7686). In this study, we have tested the hypothesis that the extent of tyrosine
      nitration depends on the intramembrane location of tyrosyl probes and on the
      nitrating species. To this end, we have synthesized membrane spanning 23-mer
      containing a single tyrosyl residue at positions 4, 8, and 12. The location of
      the tyrosine residues in the phospholipid membrane was determined by fluorescence
      and electron spin resonance techniques. Nitration was initiated by slow infusion
      of peroxynitrite, co-generated superoxide and nitric oxide ((.)NO), or a
      myeloperoxidase/hydrogen peroxide/nitrite anion (MPO/H(2)O(2)/NO(2)(-)) system.
      Results indicate that with slow infusion of peroxynitrite, nitration of
      transmembrane tyrosyl peptides was much higher (10-fold or more) than tyrosine
      nitration in aqueous phase. Peroxynitrite-dependent nitration of tyrosyl
      containing peptides increased with increasing depth of the tyrosyl residue in the
      bilayer. In contrast, MPO/H(2)O(2)/ NO(2)(-)-induced tyrosyl nitration decreased
      with increasing depth of tyrosyl residues in the membrane. Transmembrane
      nitrations of tyrosyl-containing peptides induced by both peroxynitrite and
      MPO/H(2)O(2)/NO(2)(-) were totally inhibited by (.)NO that was slowly released
      from spermine NONOate. Nitration of peptides in both systems was concentration
      dependently inhibited by unsaturated fatty acid. Concomitantly, an increase in
      lipid oxidation was detected. A mechanism involving (.)NO(2) radical is proposed
      for peroxynitrite and MPO/H(2)O(2)/NO(2)(-)-dependent transmembrane nitration
      reactions.

PMID- 12519729
TI  - Molecular imaging with PET--the future challenges.

PMID- 12519730
TI  - Against all odds, nuclear medicine has thrived.

PMID- 12519731
TI  - The Internet: the road to more effective PET.

PMID- 12519732
TI  - A combined PET/CT scanner: the path to true image fusion.
AB  - Software-based image fusion is used routinely for the alignment of functional and
      anatomical images of the brain. For other parts of the body, image registration
      is more problematic owing to differences in patient positioning, scanner bed
      profiles and the involuntary movement of internal organs. An alternative to the
      software approach is a scanner that acquires both function and anatomy during a
      single imaging session: a fusion of the technologies rather than a fusion of the
      images post hoc. Consequently, we designed and built a prototype combined PET and
      CT scanner comprising a clinical CT and a clinical PET scanner mounted together
      in a single gantry. Over 300 cancer patients have been imaged in the scanner to
      establish the clinical value of the combined PET/CT approach. The CT images were
      used to provide essentially noiseless attenuation correction factors for the PET
      data. The widespread interest created by the patient studies acquired with the
      prototype PET/CT stimulated commercial activity and several major vendors of
      medical imaging equipment now offer combined PET/CT designs. This paper reviews
      the development of the combined PET/CT scanner, and illustrates the clinical
      aspects with some typical studies in cancer patients. The potential impact on
      medical practice of the commercial availability of PET/CT scanner technology at
      affordable cost is assessed.

PMID- 12519733
TI  - The application of PET-MR image registration in the brain.
AB  - The coregistration in three-dimensional space of positron emission tomography
      (PET) and magnetic resonance (MR) image volumes has, over the last decade, become
      a matter of routine in the analysis of brain PET studies. The ability to
      objectively localize small regions of interest in PET using images more closely
      correlated to tissue structure has itself improved the effective resolution of
      PET. There are a number of highly effective software packages for image
      coregistration available in the public domain. Voxel-by-voxel coregistration,
      involving little or no intervention from the user can, on today's computing
      hardware, provide fast and accurate registration with little or no pre-processing
      and algorithms based on mutual information measures now seem to be the
      mathematical method of choice. Registration may be applied in a number of ways.
      Rigid body registration is used to match a single subject's brain scanned using
      either different imaging modalities or as serial scans with the same modality.
      Increasingly, this technique is being extended to studies of disease involving
      regional atrophy, where location and extent of tissue loss can be identified. Non
      linear registration can be used to warp a subject's brain onto a template, atlas
      or other standardized guide. While numerous examples are available of the added
      value produced by image registration in the brain, similar examples are not yet
      available from registration in the torso, where the problem is much more complex.
      It is here that newly emerging hardware such as combined PET/CT scanners may
      prove their worth.

PMID- 12519734
TI  - Initial clinical experience using a new integrated in-line PET/CT system.

PMID- 12519735
TI  - Where can FDG-PET contribute most to anatomical imaging problems?

PMID- 12519736
TI  - Simultaneous PET and NMR.
AB  - There is currently great interest in combining data from different imaging
      modalities, either by image registration methods that are performed after the
      data has been acquired or using new devices that can acquire data from two
      modalities simultaneously, or near simultaneously. In this paper a small
      prototype NMR-compatible PET scanner capable of acquiring PET images
      simultaneously with either NMR images or NMR spectra is described. In an
      associated paper [1], Pamela Garlick describes some investigations of cardiac
      metabolism that have been made using this system. One of the main challenges in
      constructing an NMR-compatible PET scanner is that photomultiplier tubes, which
      are an essential element of nearly all current PET systems, will not function in
      a high magnetic field. In collaboration with Simon Cherry and the Crump Institute
      of Biomedical Imaging at UCLA Medical School, a small (5.4 cm diameter) NMR
      compatible PET scanner that will operate within the bore of an NMR magnet has
      been developed. Long optical fibres are used to transport light from the
      scintillation crystals that form the detector head to photomultiplier tubes
      situated in a low magnetic field region several metres from the magnet. This
      system has been used to perform simultaneous PET and NMR spectroscopy
      measurements with a 9.4T spectroscopy system, and has also been used to obtain
      simultaneous PET and MR images in several MRI scanners including a 4.7T small
      bore animal imaging system. Current efforts in the development of this technology
      are directed at experimental studies on small animals, both because this is less
      demanding technically and because it is in this area that applications are likely
      to appear first. However, there is no reason in principle why human PET-MR would
      not be feasible. Below, work with the prototype system and the next stage in its
      development are described, and some of the future possibilities and challenges
      are discussed.

PMID- 12519737
TI  - Simultaneous PET and NMR--initial results from isolated, perfused rat hearts.

PMID- 12519738
TI  - Functional imaging for assessment of therapy.

PMID- 12519739
TI  - Inhaled nitric oxide modifies left ventricular diastolic stress in the presence
      of vasoactive agents in heart failure.
AB  - Nitric oxide (NO) inhalation therapy has been widely used in several diseases
      with pulmonary hypertension. However, application of NO inhalation therapy
      remains controversial in heart failure. Cardiovascular effects of inhaled NO
      (iNO) were evaluated in dogs before and after induction of heart failure with and
      without infusion of vasoactive agents. iNO did not affect the baseline left
      ventricular (LV) function or the response to isoproterenol in control conditions
      or heart failure induced by procainamide. Pulmonary vascular resistance was
      significantly decreased by iNO in heart failure with infusion of vasoactive
      agents. Unexpectedly, LV end-diastolic pressure was significantly elevated by iNO
      in heart failure in the presence of infusion of vasoactive agents independent of
      their types; either the vasodilating agents of acetylcholine and nitroglycerin or
      the vasoconstricting agents of norepinephrine and angiotensin-II. The end
      diastolic LV dimension and wall stress were also significantly increased by iNO,
      however, those at end systole were not affected. These results suggested that NO
      inhalation therapy reduced pulmonary vascular resistance, whereas in the presence
      of additional stress of vasoactive agents, it increased LV preload and end
      diastolic wall stress in heart failure.

PMID- 12519740
TI  - Bactericidal and sterilizing activities of antituberculosis drugs during the
      first 14 days.
AB  - Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2
      day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin,
      pyrazinamide, ethambutol, or streptomycin, given alone or in combinations. The
      exponential fall in colony-forming units was measured by linear regression
      coefficients of the log counts during the initial 2-day phase of rapid, drug
      determined killing and during the subsequent 12 days of much slower sterilizing
      activity. The regression coefficients during the first 2 days varied
      significantly according to the drug; the greatest effects in multiple regression
      analyses were due to isoniazid (p < 0.001) and rifampin (p = 0.027). The rapid
      kill obtained with isoniazid was unaffected by addition of other drugs, so that a
      change in activity after adding an unknown drug to isoniazid would not be
      measurable. In multiple regression analysis of the coefficients during Days 2-14,
      rifampin and streptomycin had significant effects (p = 0.007 and 0.006,
      respectively), indicating that both drugs had important sterilizing activity,
      streptomycin particularly early. Isoniazid and pyrazinamide had no significant
      effects. In analyses of combined drug regimens only, ethambutol had an effect (p
      = 0.01) in reverse direction to that of rifampin, suggesting it antagonized the
      sterilizing activity of other drugs.

PMID- 12519741
TI  - Effect of solid meal on gastric emptying of, and glycemic and cardiovascular
      responses to, liquid glucose in older subjects.
AB  - Gastric emptying is a determinant of the postprandial glycemic and cardiovascular
      responses to oral carbohydrate. We evaluated the effects of a solid meal on
      gastric emptying and the glycemic and cardiovascular responses to oral glucose in
      healthy older subjects. Ten subjects aged 72.1 +/- 1.9 yr were studied. Each
      subject had measurements of gastric emptying, blood glucose, serum insulin, blood
      pressure, and heart rate after ingestion of a 50-g glucose drink (300 ml) with
      (mixed meal) or without (liquid only) a solid meal (300 g ground beef). Gastric
      emptying of liquid was initially slightly more rapid (P < 0.05) after the mixed
      meal compared with liquid only at 5 min (92.0 +/- 1.5 vs. 96.0 +/- 1.3%) and much
      slower (P < 0.05) after 120 min. The time to peak blood glucose was less (39.0 +/
      4.0 vs. 67.5 +/- 10.3 min; P < 0.01) and blood glucose subsequently lower (P <
      0.01) after the mixed meal. The increase in serum insulin was greater (P < 0.001)
      after the mixed meal. Blood pressure fell (P < 0.05) in the first 30 min, with no
      difference between the two meals. Increase in heart rate after both meals (P <
      0.005), was greater (P < 0.05) after the mixed meal. The presence of a
      noncarbohydrate solid meal had discrepant effects on early and subsequent
      emptying of a nutrient liquid, which affects postprandial glycemia and increased
      heart rate.

PMID- 12519742
TI  - Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis
      and Socs-3.
AB  - Cytokines may cause an acquired growth hormone (GH) resistance in patients with
      inflammatory diseases. Anabolic effects of GH are mediated through activation of
      STAT5 transcription factors. We have reported that TNF-alpha suppresses hepatic
      GH receptor (GHR) gene expression, whereas the cytokine-inducible SH2-containing
      protein 1 (Cis)/suppressors of cytokine signaling (Socs) genes are upregulated by
      TNF-alpha and IL-6 and inhibit GH activation of STAT5. However, the relative
      importance of these mechanisms in inflammatory GH resistance was not known. We
      hypothesized that IL-6 would prevent GH activation of STAT5 and that this would
      involve Cis/Socs protein upregulation. GH +/- LPS was administered to TNF
      receptor 1 (TNFR1) or IL-6 null mice and wild-type (WT) controls. STAT5, STAT3,
      GHR, Socs 1-3, and Cis phosphorylation and abundance were assessed by using
      immunoblots, EMSA, and/or real time RT-PCR. TNF-alpha and IL-6 abundance were
      assessed by using ELISA. GH activated STAT5 in WT and TNFR1 or IL-6 null mice.
      LPS pretreatment prevented STAT5 activation in WT and TNFR1 null mice; however,
      STAT5 activation was preserved in IL-6 null mice. GHR abundance did not change
      with LPS administration. Inhibition of STAT5 activation by LPS was temporally
      associated with phosphorylation of STAT3 and upregulation of Cis and Socs-3
      protein in WT and TNFR1 null mice; STAT3, Cis, and Socs-3 were not induced in IL
      6 null mice. IL-6 inhibits hepatic GH signaling by upregulating Cis and Socs-3,
      which may involve activation of STAT3. Therapies that block IL-6 may enhance GH
      signaling in inflammatory diseases.

PMID- 12519743
TI  - Motilin effects on the proximal stomach in patients with functional dyspepsia and
      healthy volunteers.
AB  - This study investigates motilin effects on the proximal stomach in patients with
      functional dyspepsia (FD) and healthy volunteers. Eight healthy volunteers and 12
      patients with FD were infused with synthetic motilin or placebo. Proximal gastric
      volume was measured with a barostat at constant pressure and during isobaric
      distensions. Abdominal symptoms were scored by visual analog scales. Plasma
      motilin concentrations were measured by radioimmunoassay. Motilin concentrations
      and baseline gastric volumes were similar for patients and healthy volunteers.
      Motilin, compared with placebo, reduced gastric volume by 112 ml [F(29,195);
      confidence interval (CI) 95%] in patients and by 96 ml [F(-7,200); CI 95%] in
      healthy volunteers. In patients, motilin decreased compliance by 76 ml/mmHg
      [F(9,143); CI 95%] compared with placebo, which was similar in volunteers [66
      ml/mmHg; F(11,120); CI 95%]. Patients were more nauseous during motilin compared
      with placebo (P = 0.04), whereas healthy volunteers did not experience nausea. We
      conclude that in a fasted condition, FD patients have a similar proximal gastric
      motor response to motilin as healthy volunteers, but experience an exaggerated
      sensation of nausea.

PMID- 12519744
TI  - Age-related differences in Na+-dependent Ca2+ accumulation in rabbit hearts
      exposed to hypoxia and acidification.
AB  - In this study, we test the hypothesis that in newborn hearts (as in adults)
      hypoxia and acidification stimulate increased Na(+) uptake, in part via pH
      regulatory Na(+)/H(+) exchange. Resulting increases in intracellular Na(+)
      (Na(i)) alter the force driving the Na(+)/Ca(2+) exchanger and lead to increased
      intracellular Ca(2+). NMR spectroscopy measured Na(i) and cytosolic Ca(2+)
      concentration ([Ca(2+)](i)) and pH (pH(i)) in isolated, Langendorff-perfused 4-
      to 7-day-old rabbit hearts. After Na(+)/K(+) ATPase inhibition, hypoxic hearts
      gained Na(+), whereas normoxic controls did not [19 +/- 3.4 to 139 +/- 14.6 vs.
      22 +/- 1.9 to 22 +/- 2.5 (SE) meq/kg dry wt, respectively]. In normoxic hearts
      acidified using the NH(4)Cl prepulse, pH(i) fell rapidly and recovered, whereas
      Na(i) rose from 31 +/- 18.2 to 117.7 +/- 20.5 meq/kg dry wt. Both protocols
      caused increases in [Ca](i); however, [Ca](i) increased less in newborn hearts
      than in adults (P < 0.05). Increases in Na(i) and [Ca](i) were inhibited by the
      Na(+)/H(+) exchange inhibitor methylisobutylamiloride (MIA, 40 microM; P < 0.05),
      as well as by increasing perfusate osmolarity (+30 mosM) immediately before and
      during hypoxia (P < 0.05). The data support the hypothesis that in newborn
      hearts, like adults, increases in Na(i) and [Ca](i) during hypoxia and after
      normoxic acidification are in large part the result of increased uptake via
      Na(+)/H(+) and Na(+)/Ca(2+) exchange, respectively. However, for similar hypoxia
      and acidification protocols, this increase in [Ca](i) is less in newborn than
      adult hearts.

PMID- 12519745
TI  - Physiological modulation of CFTR activity by AMP-activated protein kinase in
      polarized T84 cells.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      activated, ATP-gated Cl(-) channel and cellular conductance regulator, but the
      detailed mechanisms of CFTR regulation and its regulation of other transport
      proteins remain obscure. We previously identified the metabolic sensor AMP
      activated protein kinase (AMPK) as a novel protein interacting with CFTR and
      found that AMPK phosphorylated CFTR and inhibited CFTR-dependent whole cell
      conductances when coexpressed with CFTR in Xenopus oocytes. To address the
      physiological relevance of the CFTR-AMPK interaction, we have now studied
      polarized epithelia and have evaluated the localization of endogenous AMPK and
      CFTR and measured CFTR activity with modulation of AMPK activity. By
      immunofluorescent imaging, AMPK and CFTR share an overlapping apical distribution
      in several rat epithelial tissues, including nasopharynx, submandibular gland,
      pancreas, and ileum. CFTR-dependent short-circuit currents (I(sc)) were measured
      in polarized T84 cells grown on permeable supports, and several independent
      methods were used to modulate endogenous AMPK activity. Activation of endogenous
      AMPK with the cell-permeant adenosine analog 5-amino-4-imidazolecarboxamide-1
      beta-d-ribofuranoside (AICAR) inhibited forskolin-stimulated CFTR-dependent I(sc)
      in nonpermeabilized monolayers and monolayers with nystatin permeabilization of
      the basolateral membrane. Raising intracellular AMP concentration in monolayers
      with basolateral membranes permeabilized with alpha-toxin also inhibited CFTR, an
      effect that was unrelated to adenosine receptors. Finally, overexpression of a
      kinase-dead mutant AMPK-alpha1 subunit (alpha1-K45R) enhanced forskolin
      stimulated I(sc) in polarized T84 monolayers, consistent with a dominant-negative
      reduction in the inhibition of CFTR by endogenous AMPK. These results indicate
      that AMPK plays a physiological role in modulating CFTR activity in polarized
      epithelia and suggest a novel paradigm for the coupling of ion transport to
      cellular metabolism.

PMID- 12519746
TI  - Reactive oxygen species are important mediators of taurine release from skeletal
      muscle cells.
AB  - The present study illustrates elements of the signal cascades involved in the
      activation of taurine efflux pathways in myotubes derived from skeletal muscle
      cells. Exposing primary skeletal muscle cells, loaded with (14)C-taurine, to 1)
      hypotonic media, 2) the phospholipase A(2) (PLA(2)) activator melittin, 3)
      anoxia, or 4) lysophosphatidyl choline (LPC) causes an increase in (14)C-taurine
      release and a concomitant production of reactive oxygen species (ROS). The
      antioxidants butulated hydroxy toluene and vitamin E inhibit the taurine efflux
      after cell swelling, anoxia, and addition of LPC. The muscle cells possess two
      separate taurine efflux pathways, i.e., a swelling- and melittin-induced pathway
      that requires 5-lipoxygenase activity for activation and a LPC-induced pathway.
      The two pathways are distinguished by their opposing sensitivity toward the anion
      channel blocker DIDS and cholesterol. These data provide evidence for PLA(2)
      products and ROS as key mediators of the signal cascade leading to taurine efflux
      in muscle.

PMID- 12519747
TI  - Sequence mutations in teleost cardiac troponin C that are permissive of high Ca2+
      affinity of site II.
AB  - Cardiac myofibrils isolated from trout heart have been demonstrated to have a
      higher sensitivity for Ca(2+) than mammalian cardiac myofibrils. Using cardiac
      troponin C (cTnC) cloned from trout and mammalian hearts, we have previously
      demonstrated that this comparatively high Ca(2+) sensitivity is due, in part, to
      trout cTnC (ScTnC) having twice the Ca(2+) affinity of mammalian cTnC (McTnC)
      over a broad range of temperatures. The amino acid sequence of ScTnC is 92%
      identical to McTnC. To determine the residues responsible for the high Ca(2+)
      affinity, the function of a number of ScTnC and McTnC mutants was characterized
      by monitoring an intrinsic fluorescent reporter that monitors Ca(2+) binding to
      site II (F27W). The removal of the COOH terminus (amino acids 90-161) from ScTnC
      and McTnC maintained the difference in Ca(2+) affinity between the truncated cTnC
      isoforms (ScNTnC and McNTnC). The replacement of Gln(29) and Asp(30) in ScNTnC
      with the corresponding residues from McNTnC, Leu and Gly, respectively, reduced
      Ca(2+) affinity to that of McNTnC. These results demonstrate that Gln(29) and
      Asp(30) in ScTnC are required for the high Ca(2+) affinity of site II.

PMID- 12519748
TI  - Robust induction of PGHS-2 by IL-1 in orbital fibroblasts results from low levels
      of IL-1 receptor antagonist expression.
AB  - Human orbital fibroblasts are more susceptible to some actions of proinflammatory
      cytokines than are fibroblasts from other anatomic regions. These cells produce
      high levels of PGE(2) when activated by cytokines. Here we report that they
      express high levels of prostaglandin-endoperoxide H synthase (PGHS)-2, the
      inflammatory cyclooxygenase, when treated with IL-1beta. This induction results
      from enhanced PGHS-2 mRNA stability and small increases in gene promoter
      activity. The enhanced transcript stability is a result of actions of the
      cytokine on the 3'-untranslated region. Orbital fibroblasts, unlike those from
      skin, fail to express high levels of IL-1 receptor antagonist (IL-1ra) when
      treated with IL-1beta, leading to loss of modulation of IL-1 action. This can be
      overcome by transiently transfecting cells with IL-1ra. Thus a decreased level of
      IL-1ra expression in orbital fibroblasts may underlie the exaggerated responses
      to IL-1 observed in those cells and, therefore, the susceptibility of the orbit
      to inflammation.

PMID- 12519750
TI  - Regulation of neuregulin/ErbB signaling by contractile activity in skeletal
      muscle.
AB  - Putative roles of neuregulin (NRG) and the ErbB receptors in skeletal muscle
      biology include myogenesis, ACh receptor expression, and glucose transport. To
      date, however, the physiological regulation of NRG/ErbB signaling has not been
      examined. We tested the hypothesis that contractile activity in vivo induces
      NRG/ErbB activation. Rat hindlimb muscle contraction was elicited with a single
      bout of electrical stimulation (RX) or treadmill running (EX). Western blot and
      immunofluorescence confirmed the expression of multiple NRG isoforms and the
      ErbB2, ErbB3, and ErbB4 receptors in adult skeletal muscle. Both RX and EX
      significantly increased phosphorylation of all NRG receptors. Furthermore,
      contraction induced a shift in the expression profile of NRG, consistent with
      proteolytic processing of a transmembrane isoform. Thus two distinct modes of
      exercise activated processing of NRG with concomitant stimulation of ErbB2,
      ErbB3, and ErbB4 signaling in vivo. To our knowledge, this is the first
      demonstration of physiological regulation of NRG/ErbB signaling in any organ and
      implicates this pathway in the metabolic and proliferative responses of skeletal
      muscle to exercise.

PMID- 12519749
TI  - HCO(3)(-)-dependent soluble adenylyl cyclase activates cystic fibrosis
      transmembrane conductance regulator in corneal endothelium.
AB  - cAMP-dependent activation of the cystic fibrosis transmembrane conductance
      regulator (CFTR) regulates fluid transport in many tissues. Secretion by the
      corneal endothelium is stimulated by cAMP and dependent on HCO(3)(-). We asked
      whether HCO(3)(-) can secondarily increase CFTR permeability in bovine corneal
      endothelial cells (BCEC) by activating soluble adenylyl cyclase (sAC).
      Immunofluorescence suggests that sAC is distributed throughout the cytoplasm.
      HCO(3)(-) (40 mM) increased cAMP concentration 42% in the presence of 50 microM
      rolipram (a phosphodiesterase 4 inhibitor), and a standard HCO(3)(-) Ringer
      solution (28.5 mM) increased apical Cl(-) permeability by 78% relative to HCO(3)(
      )-free solution. The HCO(3)(-)-dependent increase in Cl(-) permeability was
      reduced 60% by 20 mM NaHSO(3) (a weak agonist of sAC). NaHSO(3) alone increased
      apical Cl(-) permeability by only 13%. The HCO(3)(-)-dependent increase in Cl(-)
      permeability was reduced 57% in the presence of 50 microM Rp-adenosine 3',5'
      cyclic monophosphorothioate, and 86% by 50 microM 5-nitro-2-(3-phenylpropyl
      amino)benzoic acid but unaffected by 200 microM apical H(2)DIDS. CFTR
      phosphorylation was increased 23, 150, and 32% by 20 mM HSO(3)(-), 28.5 mM
      HCO(3)(-), and 28.5 mM HCO(3)(-) + 20 mM HSO(3)(-), respectively. Activation of
      apical Cl(-) permeability by 5 microM genistein was increased synergistically by
      HCO(3)(-) over that due to genistein and HCO(3)(-) alone. We conclude that
      HCO(3)(-)-stimulated sAC is a form of autocrine signaling that contributes to
      baseline cAMP production, thereby affecting baseline CFTR activity in BCEC. This
      form of autocrine signaling may be important in tissues that express sAC and
      exhibit robust HCO(3)(-) influx (e.g., ocular ciliary epithelium, choroid plexus,
      and airway epithelium).

PMID- 12519751
TI  - Identification of an apical sorting determinant in the cytoplasmic tail of
      megalin.
AB  - Megalin is the main endocytic receptor of the proximal tubule and is responsible
      for reabsorption of many filtered proteins. In contrast to other members of the
      low-density lipoprotein (LDL) receptor gene family, it is expressed on the apical
      plasma membrane (PM) of polarized epithelial cells. To identify megalin's apical
      sorting signal, we generated deletion mutants and chimeric minireceptors composed
      of complementary regions of megalin and LDL receptor-related protein (LRP) and
      assessed the distribution of the mutants in Madin-Darby canine kidney (MDCK)
      cells by immunofluorescence and cell surface biotinylation. Megalin and LRP
      minireceptors are correctly targeted to the apical and basolateral PM,
      respectively, of MDCK cells. We found that the information that directs apical
      sorting is present in the cytoplasmic tail (CT) of megalin, which contains three
      NPXY motifs, YXXO, SH3, and dileucine motifs, and a PDZ-binding motif at its COOH
      terminus. Deletion analysis established that amino acids 107-136 of the megalin
      CT containing the second NPXY-like motif are critical for apical sorting and
      targeting, whereas the regions containing the first and third NPXY motifs are
      required for efficient endocytosis. We conclude that the megalin-CT contains a
      novel apical sorting determinant and that cytoplasmic sorting machinery exists in
      MDCK cells for some apical transmembrane proteins.

PMID- 12519752
TI  - Amino acid substitutions at position 43 of NaeI endonuclease. Evidence for
      changes in NaeI structure.
AB  - NaeI endonuclease contains a 10-amino acid region with sequence similarity to the
      active site KXDG motif of DNA ligase except for leucine (Leu-43) in NaeI
      ((43)LXDG(46)). Changing Leu-43 to lysine abolishes the NaeI endonuclease
      activity and replaces it with topoisomerase and recombinase activities. Here we
      report the results of substituting Leu-43 with alanine, arginine, asparagine,
      glutamate, and histidine. Quantitating specific activities and DNA binding values
      for the mutant proteins determined the range of amino acids at position 43 that
      alter NaeI mechanism. Substituting alanine, asparagine, glutamate, and histidine
      for Leu-43 maintained endonuclease activity, but at a lower level. On the other
      hand, substituting positively charged arginine, like lysine at position 43,
      converted NaeI to a topoisomerase with no observable double-strand cleavage
      activity. The specific activities of NaeI-43K and NaeI-43R and their relative
      sensitivities to salt, the topoisomerase-inhibiting drug N-[4-(9-acridinylamino)
      3-methoxyphenyl]methane-sulfonamide (amsacrine) and single-stranded DNA showed
      that the two activities are similar. The effect of placing a positive charge at
      position 43 on NaeI structure was determined by measuring (for NaeI and NaeI-43K)
      relative susceptibilities to proteolysis, UV, circular dichroism spectra, and
      temperature melting transitions. The results provide evidence that a positive
      charge at position 43 induces dramatic changes in NaeI structure that affect both
      the Endo and Topo domains of NaeI. The identification of four putative DNA ligase
      motifs in NaeI leads us to speculate that structural changes that superimpose
      these motifs on the ligase structure may account for the changes in activity.

PMID- 12519753
TI  - The herpes simplex virus type 1 DNA polymerase processivity factor increases
      fidelity without altering pre-steady-state rate constants for polymerization or
      excision.
AB  - Pre-steady-state and steady-state kinetics of nucleotide incorporation and
      excision were used to assess potential mechanisms by which the fidelity of the
      herpes simplex virus type 1 DNA polymerase catalytic subunit (Pol) is enhanced by
      its processivity factor, UL42. UL42 had no effect on the pre-steady-state rate
      constant for correct nucleotide incorporation (150 s(-1)) nor on the primary rate
      limiting conformational step. However, the equilibrium dissociation constant for
      the enzyme in a stable complex with primer-template was 44 nm for Pol and 7.0 nm
      for Pol/UL42. The catalytic subunit and holoenzyme both selected against
      incorrect nucleotide incorporation predominantly at the level of nucleotide
      affinity, although UL42 slowed by 4-fold the maximum rate of incorporation of
      incorrect, compared with correct, nucleotide. Pol, with or without UL42, cleaved
      matched termini at a slower rate than mismatched ones, but UL42 did not
      significantly alter the pre-steady-state rate constant for mismatch excision (
      approximately 16 s(-1)). The steady-state rate constant for nucleotide addition
      was 0.09 s(-1) and 0.03 s(-1) for Pol and Pol/UL42, respectively, and enzyme
      dissociation was the rate-limiting step. The longer half-life for DNA complexes
      with Pol/UL42 (23 s) compared with that with Pol (8 s) affords a greater
      probability for excision when a misincorporation event does occur, accounting
      predominantly for the failure of Pol/UL42 to accumulate mismatched product at
      moderate nucleotide concentrations.

PMID- 12519754
TI  - Mechanism of loading the Escherichia coli DNA polymerase III beta sliding clamp
      on DNA. Bona fide primer/templates preferentially trigger the gamma complex to
      hydrolyze ATP and load the clamp.
AB  - The Escherichia coli DNA polymerase III gamma complex clamp loader assembles the
      ring-shaped beta sliding clamp onto DNA. The core polymerase is tethered to the
      template by beta, enabling processive replication of the genome. Here we
      investigate the DNA substrate specificity of the clamp-loading reaction by
      measuring the pre-steady-state kinetics of DNA binding and ATP hydrolysis using
      elongation-proficient and deficient primer/template DNA. The ATP-bound clamp
      loader binds both elongation-proficient and deficient DNA substrates either in
      the presence or absence of beta. However, elongation-proficient DNA
      preferentially triggers gamma complex to release beta onto DNA with concomitant
      hydrolysis of ATP. Binding to elongation-proficient DNA converts the gamma
      complex from a high affinity ATP-bound state to an ADP-bound state having a 10(5)
      fold lower affinity for DNA. Steady-state binding assays are misleading,
      suggesting that gamma complex binds much more avidly to non-extendable
      primer/template DNA because recycling to the high affinity binding state is rate
      limiting. Pre-steady-state rotational anisotropy data reveal a dynamic
      association-dissociation of gamma complex with extendable primer/templates
      leading to the diametrically opposite conclusion. The strongly favored dynamic
      recognition of extendable DNA does not require the presence of beta. Thus, the
      gamma complex uses ATP binding and hydrolysis as a mechanism for modulating its
      interaction with DNA in which the ATP-bound form binds with high affinity to DNA
      but elongation-proficient DNA substrates preferentially trigger hydrolysis of ATP
      and conversion to a low affinity state.

PMID- 12519755
TI  - Differential regulation of CXCR4-mediated T-cell chemotaxis and mitogen-activated
      protein kinase activation by the membrane tyrosine phosphatase, CD45.
AB  - The chemokine receptor CXCR4 and its cognate ligand, stromal cell-derived factor
      1alpha (CXCL12), regulate lymphocyte trafficking and play an important role in
      host immune surveillance. However, the molecular mechanisms involved in CXCL12
      induced and CXCR4-mediated chemotaxis of T-lymphocytes are not completely
      elucidated. In the present study, we examined the role of the membrane tyrosine
      phosphatase CD45, which regulates antigen receptor signaling in CXCR4-mediated
      chemotaxis and mitogen-activated protein kinase (MAPK) activation in T-cells. We
      observed a significant reduction in CXCL12-induced chemotaxis in the CD45
      negative Jurkat cell line (J45.01) as compared with the CD45-positive control
      (JE6.1) cells. Expression of a chimeric protein containing the intracellular
      phosphatase domain of CD45 was able to partially restore CXCL12-induced
      chemotaxis in the J45.01 cells. However, reconstitution of CD45 into the J45.01
      cells restored the CXCL12-induced chemotaxis to about 90%. CD45 had no
      significant effect on CXCL12 or human immunodeficiency virus gp120-induced
      internalization of the CXCR4 receptor. Furthermore, J45.01 cells showed a slight
      enhancement in CXCL12-induced MAP kinase activity as compared with the JE6.1
      cells. We also observed that CXCL12 treatment enhanced the tyrosine
      phosphorylation of CD45 and induced its association with the CXCR4 receptor.
      Pretreatment of T-cells with the lipid raft inhibitor, methyl-beta-cyclodextrin,
      blocked the association between CXCR4 and CD45 and markedly abolished CXCL12
      induced chemotaxis. Comparisons of signaling pathways induced by CXCL12 in JE6.1
      and J45.01 cells revealed that CD45 might moderately regulate the tyrosine
      phosphorylation of the focal adhesion components the related adhesion focal
      tyrosine kinase/Pyk2, focal adhesion kinase, p130Cas, and paxillin. CD45 has also
      been shown to regulate CXCR4-mediated activation and phosphorylation of T-cell
      receptor downstream effectors Lck, ZAP-70, and SLP-76. Our results show that CD45
      differentially regulates CXCR4-mediated chemotactic activity and MAPK activation
      by modulating the activities of focal adhesion components and the downstream
      effectors of the T-cell receptor.

PMID- 12519756
TI  - Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of
      transferring plasmid DNA into cells.
AB  - We constructed multimers of the TAT-(47-57) peptide. This polycationic peptide is
      known to be a protein and particle transduction domain and at the same time to
      comprise a nuclear localization function. Here we show that oligomers of the TAT
      (47-57) peptide compact plasmid DNA to nanometric particles and stabilize DNA
      toward nuclease degradation. At optimized vector compositions, these peptides
      mediated gene delivery to cells in culture 6-8-fold more efficiently than poly-L
      arginine or the mutant TAT(2)-M1. When DNA was precompacted with TAT peptides and
      polyethyleneimine (PEI), Superfect, or LipofectAMINE was added, transfection
      efficiency was enhanced up to 390-fold compared with the standard vectors. As
      early as after 4 h of transfection, reporter gene expression mediated by TAT
      containing complexes was higher than the 24-h transfection level achieved with a
      standard PEI transfection. When cells were cell cycle-arrested by serum
      starvation or aphidicolin, TAT-mediated transfection was 3-fold more efficient
      than a standard PEI transfection in proliferating cells. In primary nasal
      epithelial cells and upon intratracheal instillation in vivo, TAT-containing
      complexes were superior to standard PEI vectors. These data together with
      confocal imaging of TAT-DNA complexes in cells support the hypothesis that the
      TAT nuclear localization sequence function is involved in enhancing gene
      transfer.

PMID- 12519757
TI  - Mode of inhibition of short-patch base excision repair by thymine glycol within
      clustered DNA lesions.
AB  - Clustered DNA damage, where two or more lesions are located proximally to each
      other, is frequently induced by ionizing radiation. Individual base lesions
      within a cluster are repaired by base excision repair. In this study we addressed
      the question of how thymine glycol (Tg) within a cluster would affect the repair
      of opposing lesions by human cell extracts. We have found that Tg located
      opposite to an abasic site does not affect cleavage of this site by
      apurinic/apyrimidinic (AP) endonuclease. However, Tg significantly compromised
      the next step of the repair. Although purified DNA polymerase beta was able to
      incorporate the correct nucleotide (dAMP) opposite to Tg, the rate of
      incorporation was reduced by 3-fold. Tg does not affect 5'-sugar phosphate
      removal by the 2-deoxyribose-5-phosphate (dRP) lyase activity of DNA polymerase
      beta, but further processing of the strand break by purified DNA ligase III was
      slightly diminished. In agreement with these findings, although an AP site
      located opposite to Tg was efficiently incised in human cell extract, only a
      limited amount of fully repaired product was observed, suggesting that such
      clustered DNA lesions may have a significantly increased lifetime in human cells
      compared with similar single-standing lesions.

PMID- 12519758
TI  - Substrate specificity of human endonuclease III (hNTH1). Effect of human APE1 on
      hNTH1 activity.
AB  - Base excision repair of oxidized pyrimidines in human DNA is initiated by the DNA
      N-glycosylase/apurinic/apyrimidinic (AP) lyase, human NTH1 (hNTH1), the homolog
      of Escherichia coli endonuclease III (Nth). In contrast to Nth, the DNA N
      glycosylase activity of hNTH1 is 7-fold greater than its AP lyase activity when
      the DNA substrate contains a thymine glycol (Tg) opposite adenine (Tg:A)
      (Marenstein, D. R., Ocampo, M. T. A., Chan, M. K., Altamirano, A., Basu, A. K.,
      Boorstein, R. J., Cunningham, R. P., and Teebor, G. W. (2001) J. Biol. Chem. 276,
      21242-21249). When Tg is opposite guanine (Tg:G), the two activities are of the
      same specific activity as the AP lyase activity of hNTH1 against Tg:A (Ocampo, M.
      T. A., Chaung, W., Marenstein, D. R., Chan, M. K., Altamirano, A., Basu, A. K.,
      Boorstein, R. J., Cunningham, R. P., and Teebor, G. W. (2002) Mol. Cell. Biol.
      22, 6111-6121). We demonstrate here that hNTH1 was inhibited by the product of
      its DNA N-glycosylase activity directed against Tg:G, the AP:G site. In contrast,
      hNTH1 was not as inhibited by the AP:A site arising from release of Tg from Tg:A.
      Addition of human APE1 (AP endonuclease-1) increased dissociation of hNTH1 from
      the DNA N-glycosylase-generated AP:A site, resulting in abrogation of AP lyase
      activity and an increase in turnover of the DNA N-glycosylase activity of hNTH1.
      Addition of APE1 did not abrogate hNTH1 AP lyase activity against Tg:G. The
      stimulatory protein YB-1 (Marenstein et al.), added to APE1, resulted in an
      additive increase in both activities of hNTH1 regardless of base pairing. Tg:A is
      formed by oxidative attack on thymine opposite adenine. Tg:G is formed by
      oxidative attack on 5-methylcytosine opposite guanine (Zuo, S., Boorstein, R. J.,
      and Teebor, G. W. (1995) Nucleic Acids Res. 23, 3239-3243). It is possible that
      the in vitro substrate selectivity of mammalian NTH1 and the concomitant
      selective stimulation of activity by APE1 are indicative of selective repair of
      oxidative damage in different regions of the genome.

PMID- 12519759
TI  - Preadipocyte conversion to macrophage. Evidence of plasticity.
AB  - Preadipocytes are present throughout adult life in adipose tissues and can
      proliferate and differentiate into mature adipocytes according to the energy
      balance. An increasing number of reports demonstrate that cells from adipose
      lineages (preadipocytes and adipocytes) and macrophages share numerous functional
      or antigenic properties. No large scale comparison reflecting the phenotype
      complexity has been performed between these different cell types until now. We
      used profiling analysis to define the common features shared by preadipocyte,
      adipocyte, and macrophage populations. Our analysis showed that the preadipocyte
      profile is surprisingly closer to the macrophage than to the adipocyte profile.
      From these data, we hypothesized that in a macrophage environment preadipocytes
      could effectively be converted into macrophages. We injected labeled stroma
      vascular cells isolated from mouse white adipose tissue or 3T3-L1 preadipocyte
      cell line into the peritoneal cavity of nude mice and investigated changes in
      their phenotype. Preadipocytes rapidly and massively acquired high phagocytic
      activity and index. 60-70% of preadipocytes also expressed five macrophage
      specific antigens: F4/80, Mac-1, CD80, CD86, and CD45. These values were similar
      to those observed for peritoneal macrophages. In vitro experiments showed that
      cell-to-cell contact between preadipocytes and peritoneal macrophages partially
      induced this preadipocyte phenotype conversion. Overall, these results suggest
      that preadipocyte and macrophage phenotypes are very similar and that
      preadipocytes have the potential to be very efficiently and rapidly converted
      into macrophages. This work emphasizes the great cellular plasticity of adipose
      precursors and reinforces the link between adipose tissue and innate immunity
      processes.

PMID- 12519760
TI  - Substrate recognition and molecular mechanism of fatty acid hydroxylation by
      cytochrome P450 from Bacillus subtilis. Crystallographic, spectroscopic, and
      mutational studies.
AB  - Cytochrome P450 isolated from Bacillus subtilis (P450(BSbeta); molecular mass, 48
      kDa) catalyzes the hydroxylation of a long-chain fatty acid (e.g. myristic acid)
      at the alpha- and beta-positions using hydrogen peroxide as an oxidant. We report
      here on the crystal structure of ferric P450(BSbeta) in the substrate-bound form,
      determined at a resolution of 2.1 A. P450(BSbeta) exhibits a typical P450 fold.
      The substrate binds to a specific channel in the enzyme and is stabilized through
      hydrophobic interactions of its alkyl side chain with some hydrophobic residues
      on the enzyme as well as by electrostatic interaction of its terminal carboxylate
      with the Arg(242) guanidium group. These interactions are responsible for the
      site specificity of the hydroxylation site in which the alpha- and beta-positions
      of the fatty acid come into close proximity to the heme iron sixth site. The
      fatty acid carboxylate group interacts with Arg(242) in the same fashion as has
      been reported for the active site of chloroperoxidase, His(105)-Glu(183), which
      is an acid-base catalyst in the peroxidation reactions. On the basis of these
      observations, a possible mechanism for the hydroxylation reaction catalyzed by
      P450(BSbeta) is proposed in which the carboxylate of the bound-substrate fatty
      acid assists in the cleavage of the peroxide O-O bond.

PMID- 12519761
TI  - Glucose 6-phosphate produced by gluconeogenesis and by glucokinase is equally
      effective in activating hepatic glycogen synthase.
AB  - Glucose 6-phosphate (Glc-6-P) produced in cultured hepatocytes by direct
      phosphorylation of glucose or by gluconeogenesis from dihydroxyacetone (DHA) was
      equally effective in activating glycogen synthase (GS). However, glycogen
      accumulation was higher in hepatocytes incubated with glucose than in those
      treated with DHA. This difference was attributed to decreased futile cycling
      through GS and glycogen phosphorylase (GP) in the glucose-treated hepatocytes,
      owing to the partial inactivation of GP induced by glucose. Our results indicate
      that the gluconeogenic pathway and the glucokinase-mediated phosphorylation of
      glucose deliver their common product to the same Glc-6-P pool, which is
      accessible to liver GS. As observed in the treatment with glucose, incubation of
      cultured hepatocytes with DHA caused the translocation of GS from a uniform
      cytoplasmic distribution to the hepatocyte periphery and a similar pattern of
      glycogen deposition. We hypothesize that Glc-6-P has a major role in glycogen
      metabolism not only by determining the activation state of GS but also by
      controlling its subcellular distribution in the hepatocyte.

PMID- 12519763
TI  - Identification of an upstream enhancer in the mouse laminin alpha 1 gene defining
      its high level of expression in parietal endoderm cells.
AB  - Laminin-1 is the major component of the embryonic basement membrane and consists
      of alpha1, beta1, and gamma1 chains. The expression of laminin-1 is induced in
      mouse F9 embryonal carcinoma cells upon differentiation into parietal endoderm
      through transcriptional up-regulation of the genes encoding these subunits. Here,
      we identified a 435-bp enhancer in the 5'-flanking region of the mouse laminin
      alpha1 (LAMA1) gene that activated its transcription in a differentiation
      dependent manner. This enhancer was also active in PYS-2 parietal yolk sac
      derived cells but not in NIH/3T3 fibroblasts, indicating that it was a parietal
      endoderm-specific enhancer. This enhancer was also active in Engelbreth-Holm
      Swarm (EHS) tumor-derived cells characterized by excessive production of laminin
      1 and other basement membrane components, suggesting that EHS tumors have a
      transcriptional control mechanism similar to that of parietal endoderm cells.
      Electrophoretic mobility shift analyses revealed four protein binding sites (PBS1
      PBS4) in the 435-bp region. However, these DNA-binding proteins were detected not
      only in parietal endoderm cells (i.e. differentiated F9 cells, PYS-2 cells, and
      EHS tumor-derived cells) but also in undifferentiated F9 cells and NIH/3T3 cells.
      Mutational analyses revealed that three of these binding sites (PBS2, PBS3, and
      PBS4) function synergistically to confer the parietal endoderm-specific enhancer
      activity. The proteins binding to PBS2 and PBS4 were identified as the Sp1/Sp3
      family of transcription factors and YY1, respectively.

PMID- 12519762
TI  - Repression of farnesoid X receptor during the acute phase response.
AB  - The acute phase response is associated with changes in the hepatic expression of
      genes involved in lipid metabolism. Nuclear hormone receptors that heterodimerize
      with retinoid X receptor (RXR), such as thyroid receptors, peroxisome
      proliferator-activated receptors, and liver X receptors, modulate lipid
      metabolism. We recently demonstrated that these nuclear hormone receptors are
      repressed during the acute phase response induced by lipopolysaccharide (LPS),
      consistent with the known decreases in genes that they regulate. In the present
      study, we show that LPS significantly decreases farnesoid X receptor (FXR) mRNA
      in mouse liver as early as 8 h after LPS administration, and this decrease was
      dose-dependent with the half-maximal effect observed at 0.5 microg/100 g of body
      weight. Gel-shift experiments demonstrated that DNA binding activity to an FXR
      response element (IR1) is significantly reduced by LPS treatment. Supershift
      experiments demonstrated that the shifted protein-DNA complex contains FXR and
      RXR. Furthermore, the expression of FXR target genes, SHP and apoCII, were
      significantly reduced by LPS (70 and 60%, respectively). Also, LPS decreases
      hepatic LRH expression in mouse, which may explain the reduced expression of
      CYP7A1 in the face of SHP repression. In Hep3B human hepatoma cells, both tumor
      necrosis factor (TNF) and interleukin-1 (IL-1) significantly decreased FXR mRNA,
      whereas IL-6 did not have any effect. TNF and IL-1 also decreased the DNA binding
      activity to an IR1 response element and the expression of SHP and apoCII.
      Importantly, TNF and IL-1 almost completely blocked the expression of luciferase
      activity linked to a FXR response element promoter construct transfected into
      Hep3B cells. Together with our earlier studies on the repression of RXRs,
      peroxisome proliferator-activated receptors, LXRs, thyroid receptors,
      constitutive androstane receptor, and pregnane X receptor, these results suggest
      that decreases in nuclear hormone receptors are major contributors to the
      decreased gene expression that occurs in the negative acute phase response.

PMID- 12519764
TI  - Calmodulin-dependent and -independent activation of endothelial nitric-oxide
      synthase by heat shock protein 90.
AB  - Endothelial nitric oxide synthase (eNOS), which generates the endogenous
      vasodilator, nitric oxide (NO), is highly regulated by post-translational
      modifications and protein interactions. Heat shock protein 90 (HSP90) binds
      directly to eNOS, augmenting NO production. We have used purified proteins to
      characterize further the mechanism by which HSP90 increases eNOS activity at low
      (100 nm) and high (10 microm) Ca(2+) levels. In the presence of calmodulin (CaM),
      HSP90 increased eNOS activity dose dependently at both low and high Ca(2+)
      concentrations. This effect was abolished by the specific HSP90 inhibitor
      geldanamycin (GA) at both calcium concentrations. The EC(50) values of eNOS for
      both Ca(2+) and CaM were decreased in the presence of HSP90. HSP90 also
      significantly increased the rate of NADPH-dependent cytochrome c reduction by
      eNOS at both low and high Ca(2+) concentrations. HSP90 bound to eNOS in a dose
      dependent manner, and the amount of bound HSP90 also increased with increasing
      Ca(2+)/CaM. At 100 nm Ca(2+), HSP90 promoted dose-dependent CaM binding to eNOS
      that was fully inhibitable by GA. At high calcium, HSP90 did not affect CaM
      binding to eNOS, but GA inhibited HSP90 binding to eNOS. At high Ca(2+), HSP90
      caused the V(max) of eNOS for l-arginine to increase by 2-fold, but the K(m) of
      eNOS was unchanged. HSP90 bound preferentially to CaM-prebound eNOS and
      significantly increased both its NO synthesis and reductase activities. These
      data support that HSP90 promotes eNOS activity by two mechanisms: (i) a CaM
      dependent mechanism operative at low Ca(2+) concentrations, characterized by an
      increase in the affinity of eNOS for CaM and (ii) a CaM-independent mechanism
      apparent at high Ca(2+) concentrations, characterized by stimulation of eNOS
      reductase activity without further change in CaM binding. These studies
      contribute to our understanding of eNOS activation by HSP90 and provide a basis
      for in vitro studies of other eNOS-interacting proteins.

PMID- 12519765
TI  - Chromosomal region maintenance 1 (CRM1)-dependent nuclear export of Smad
      ubiquitin regulatory factor 1 (Smurf1) is essential for negative regulation of
      transforming growth factor-beta signaling by Smad7.
AB  - Smad ubiquitin regulatory factor 1 (Smurf1), a HECT type E3 ubiquitin ligase,
      interacts with inhibitory Smad7 and induces translocation of Smad7 to the
      cytoplasm. Smurf1 then associates with the transforming growth factor (TGF)-beta
      type I receptor, TbetaR-I, enhancing turnover. However, the mechanism of nuclear
      export of Smad7 by Smurf1 has not been elucidated. Here we identified a
      functional nuclear export signal (NES) in a C-terminal region of Smurf1. In
      transfected cells, the Smurf1-Smad7 complex was accumulated in the cytoplasm by
      the nuclear export receptor, CRM1; this action was prevented by treatment with
      leptomycin B, a specific inactivator of CRM1 function. A green fluorescence
      protein fusion protein containing the C-terminal NES motif of Smurf1, located in
      the cytoplasm, accumulated in the nucleus following treatment with leptomycin B.
      Moreover, Smurf1 was shown to bind physically to CRM1 through NES, and nuclear
      export of the Smurf1-Smad7 complex was prevented by mutations of Smurf1 within
      the NES. Finally, the Smurf1 NES mutant reduced inhibition by Smad7 of the
      transcriptional activation induced by TGF-beta. These results thus suggest that
      CRM1-dependent nuclear export of Smurf1 is essential for the negative regulation
      of TGF-beta signaling by Smad7.

PMID- 12519766
TI  - The solution structure of molt-inhibiting hormone from the Kuruma prawn
      Marsupenaeus japonicus.
AB  - Molting in crustaceans is controlled by molt-inhibiting hormone (MIH) and
      ecdysteroids. It is presumed that MIH inhibits the synthesis and the secretion of
      ecdysteroids by the Y-organ, resulting in molt suppression. The amino acid
      sequence of MIH is similar to that of crustacean hyperglycemic hormone (CHH), and
      therefore, they form a peptide family referred to as the CHH family. Most of the
      CHH family peptides show no cross-activity, whereas a few peptides show multiple
      hormonal activities. To reveal the structural basis of this functional
      specificity, we determined the solution structure of MIH from the Kuruma prawn
      Marsupenaeus japonicus and compared the solution structure of MIH with a homology
      modeled structure of M. japonicus CHH. The solution structure of MIH consisted of
      five alpha-helices and no beta-structures, constituting a novel structural motif.
      The homology-modeled structure of M. japonicus CHH was very similar to the
      solution structure of MIH with the exception of the absence of the N-terminal
      alpha-helix and the C-terminal tail, which were sterically close to each other.
      The surface properties of MIH around this region were quite different from those
      of CHH. These results strongly suggest that this region is a functionally
      important site for conferring molt-inhibiting activity.

PMID- 12519767
TI  - In vitro selection of adenine-dependent hairpin ribozymes.
AB  - Adenine-dependent hairpin ribozymes were isolated by in vitro selection from a
      degenerated hairpin ribozyme population. Two new adenine-dependent ribozymes
      catalyze their own reversible cleavage in the presence of free adenine. Both
      aptamers have Mg(2+) requirements for adenine-assisted cleavage similar to the
      wild-type hairpin ribozyme. Cleavage kinetics studies in the presence of various
      other small molecules were compared. The data suggest that adenine does not
      induce RNA self-cleavage in the same manner for both aptamers. In addition,
      investigations of pH effects on catalytic rates show that both adenine-dependent
      aptamers are more active in basic conditions, suggesting that they use new
      acid/base catalytic strategies in which adenine could be involved directly. The
      discovery of hairpin ribozymes dependent on adenine for their reversible self
      cleavage presents considerable biochemical and evolutionary interests because we
      show that RNA is able to use exogenous reactive molecules to enhance its own
      catalytic activity. Such a mechanism may have been a means by which the ribozymes
      of the RNA world enlarged their chemical repertoire.

PMID- 12519768
TI  - Functional expression and characterization of an archaeal aquaporin. AqpM from
      methanothermobacter marburgensis.
AB  - Researchers have described aquaporin water channels from diverse eubacterial and
      eukaryotic species but not from the third division of life, Archaea.
      Methanothermobacter marburgensis is a methanogenic archaeon that thrives under
      anaerobic conditions at 65 degrees C. After transfer to hypertonic media, M.
      marburgensis sustained cytoplasmic shrinkage that could be prevented with
      HgCl(2). We amplified aqpM by PCR from M. marburgensis DNA. Like known
      aquaporins, the open reading frame of aqpM encodes two tandem repeats each
      containing three membrane-spanning domains and a pore-forming loop with the
      signature motif Asn-Pro-Ala (NPA). Unlike other known homologs, the putative
      Hg(2+)-sensitive cysteine was found proximal to the first NPA motif in AqpM,
      rather than the second. Moreover, amino acids distinguishing water-selective
      homologs from glycerol-transporting homologs were not conserved in AqpM. A fusion
      protein, 10-His-AqpM, was expressed and purified from Escherichia coli. AqpM
      reconstituted into proteoliposomes was shown by stopped-flow light scattering
      assays to have elevated osmotic water permeability (P(f) = 57 microm x s(-1)
      versus 12 microm x s(-1) of control liposomes) that was reversibly inhibited with
      HgCl(2). Transient, initial glycerol permeability was also detected. AqpM
      remained functional after incubations at temperatures above 80 degrees C and
      formed SDS-stable tetramers. Our studies of archaeal AqpM demonstrate the
      ubiquity of aquaporins in nature and provide new insight into protein structure
      and transport selectivity.

PMID- 12519769
TI  - ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in
      response to reoxygenation.
AB  - The ATR kinase phosphorylates both p53 and Chk1 in response to extreme hypoxia
      (oxygen concentrations of less than 0.02%). In contrast to ATR, loss of ATM does
      not affect the phosphorylation of these or other targets in response to hypoxia.
      However, hypoxia within tumors is often transient and is inevitably followed by
      reoxygenation. We hypothesized that ATR activity is induced under hypoxic
      conditions because of growth arrest and ATM activity increases in response to the
      oxidative stress of reoxygenation. Using the comet assay to detect DNA damage, we
      find that reoxygenation induced significant amounts of DNA damage. Two ATR/ATM
      targets, p53 serine 15 and histone H2AX, were both phosphorylated in response to
      hypoxia in an ATR-dependent manner. These phosphorylations were then maintained
      in response to reoxygenation-induced DNA damage in an ATM-dependent manner. The
      reoxygenation-induced p53 serine 15 phosphorylation was inhibited by the addition
      of N-acetyl-l-cysteine (NAC), indicating that free radical-induced DNA damage was
      mediated by reactive oxygen species. Taken together these data implicate both ATR
      and ATM as critical roles in the response of hypoxia and reperfusion in solid
      tumors.

PMID- 12519771
TI  - How additives influence the refolding of immunoglobulin-folded proteins in a
      stepwise dialysis system. Spectroscopic evidence for highly efficient refolding
      of a single-chain Fv fragment.
AB  - The gradual removal of the denaturing reagent guanidine HCl (GdnHCl) using
      stepwise dialysis with the introduction of an oxidizing reagent and l-arginine
      resulted in the highly efficient refolding of various denatured single-chain Fv
      fragments (scFvs) from inclusion bodies expressed in Escherichia coli. In this
      study, the influence of the additives on the intermediates in scFv refolding was
      carefully analyzed on the basis of the stepwise dialysis, and it was revealed
      that the additive effect critically changes the pathway of scFv refolding.
      Circular dichroism and tryptophan fluorescence emission spectroscopies
      demonstrated that distinct secondary and tertiary structures were formed upon
      dialysis from 2 m GdnHCl to 1 m GdnHCl, and 4,4'-dianilino-1,1'-binaphthyl-5,5'
      disulfonic acid dipotassium salt binding analysis indicated that the addition of
      l-arginine to the stepwise dialysis system effectively stabilized the exposed
      hydrophobic area on the scFv. Quantification of the free thiol groups in the scFv
      by means of Ellman's assay revealed that there was a particular stage in which
      most of the free thiol groups were oxidized and that adding an oxidizing reagent
      (the oxidized form of glutathione, GSSG) at that stage was important for complete
      refolding of the scFv. The particular stage depended on the nature of the
      refolding solution, especially on whether l-arginine was present. Spontaneous
      folding at the 1 m GdnHCl stage resulted in a structure in which a free thiol
      group accessed to the proper one for correct disulfide linkage; however, the
      addition of l-arginine resulted in the formation of a partially folded
      intermediate without disulfide linkages. Mass spectrometry experiments on
      alkylated scFv were carried out at each stage to determine the effects of l
      arginine. The spectroscopic studies revealed two different pathways for scFv
      refolding in the stepwise dialysis system, pathways that depended on whether l
      arginine was present. Controlled coupling of the effects of GSSG and l-arginine
      led to the complete refolding of scFv in the stepwise dialysis.

PMID- 12519770
TI  - Vortex-mediated mechanical stress induces integrin-dependent cell adhesion
      mediated by inositol 1,4,5-trisphosphate-sensitive Ca2+ release in THP-1 cells.
AB  - In the downstream regions of stenotic vessels, cells are subjected to a vortex
      motion under low shear forces, and atherosclerotic plaques tend to be localized.
      It has been reported that such a change of shear force on endothelial cells has
      an atherogenic effect by inducing the expression of adhesion molecules. However,
      the effect of vortex-induced mechanical stress on leukocytes has not been
      investigated. In this study, to elucidate whether vortex flow can affect the cell
      adhesive property, we have examined the effect of vortex-mediated mechanical
      stress on integrin activation in THP-1 cells, a monocytic cell line, and its
      signaling mechanisms. When cells are subjected to vortex flow at 400-2,000 rpm,
      integrin-dependent cell adhesion to vascular cell adhesion molecule-1 or
      fibronectin increased in a speed- and time-dependent manner. Next, to examine the
      role of Ca(2+) in this integrin activation, various pharmacological inhibitors
      involved in Ca(2+) signaling were tested to inhibit the cell adhesion.
      Pretreatment of cells with BAPTA-AM, thapsigargin +NiCl(2), or U-73122 (a
      phospholipase C inhibitor) inhibited cell adhesion induced by vortex-mediated
      mechanical stress. We also found that W7 (a calmodulin inhibitor) blocked the
      cell adhesion. However, pretreatment of cells with GdCl(3), NiCl(2), or ryanodine
      did not affect the cell adhesion. These data indicate that vortex-mediated
      mechanical stress induces integrin activation through calmodulin and inositol
      1,4,5-trisphosphate-mediated Ca(2+) releases from intracellular Ca(2+) stores in
      THP-1 cells.

PMID- 12519772
TI  - The 1.92-A structure of Streptomyces coelicolor A3(2) CYP154C1. A new
      monooxygenase that functionalizes macrolide ring systems.
AB  - Evolutionary links between cytochrome P450 monooxygenases, a superfamily of
      extraordinarily divergent heme-thiolate proteins catalyzing a wide array of
      NADPH/NADH- and O(2)-dependent reactions, are becoming better understood because
      of availability of an increasing number of fully sequenced genomes. Among other
      reactions, P450s catalyze the site-specific oxidation of the precursors to
      macrolide antibiotics in the genus Streptomyces introducing regiochemical
      diversity into the macrolide ring system, thereby significantly increasing
      antibiotic activity. Developing effective uses for Streptomyces enzymes in
      biosynthetic processes and bioremediation requires identification and engineering
      of additional monooxygenases with activities toward a diverse array of small
      molecules. To elucidate the molecular basis for substrate specificity of
      oxidative enzymes toward macrolide antibiotics, the x-ray structure of CYP154C1
      from Streptomyces coelicolor A3(2) was determined (Protein Data Bank code ).
      Relocation of certain common P450 secondary structure elements, along with a
      novel structural feature involving an additional beta-strand transforming the
      five-stranded beta-sheet into a six-stranded variant, creates an open cleft
      shaped substrate-binding site between the two P450 domains. High sequence
      similarity to macrolide monooxygenases from other microbial species translates
      into catalytic activity of CYP154C1 toward both 12- and 14-membered ring
      macrolactones in vitro.

PMID- 12519773
TI  - The cyclin D1-dependent kinase associates with the pre-replication complex and
      modulates RB.MCM7 binding.
AB  - The capacity of the cyclin D-dependent kinase to promote G(1) progression through
      modulation of RB.E2F is well documented. We now demonstrate that the cyclin
      D1/CDK4 kinase binds to components of the MCM complex. MCM7 and MCM3 were
      identified as cyclin D1-binding proteins. Catalytically active cyclin D1/CDK4
      complexes were incorporated into chromatin-bound protein complexes with the same
      kinetics as MCM7 and MCM3, where they associated specifically with MCM7. Although
      the cyclin D1-dependent kinase did not phosphorylate MCM7, active cyclin D1/CDK4,
      but not cyclin E/CDK2, did catalyze the dissociation of an RB.MCM7 complex.
      Finally, expression of an active D1/CDK4 kinase but not cyclin E/CDK2 promoted
      the removal of RB from chromatin-bound protein complexes. Our data suggest that
      D1/CDK4 complexes play a direct role in altering an inhibitory RB.MCM7 complex
      possibly allowing for setting of the origin in preparation for DNA replication.

PMID- 12519774
TI  - The heparin/heparan sulfate 2-O-sulfatase from Flavobacterium heparinum. A
      structural and biochemical study of the enzyme active site and saccharide
      substrate specificity.
AB  - In the previous paper (Myette, J. R., Shriver, Z., Claycamp, C., McLean, M. W.,
      Venkataraman, G., and Sasisekharan, R. (2003) J. Biol. Chem. 278, 12157-12166),
      we described the molecular cloning, recombinant expression, and preliminary
      biochemical characterization of the heparin/heparan sulfate 2-O-sulfatase from
      Flavobacterium heparinum. In this paper, we extend our structure-function
      investigation of the 2-O-sulfatase. First, we have constructed a homology-based
      structural model of the enzyme active site, using as a framework the available
      crystallographic data for three highly related arylsulfatases. In this model, we
      have identified important structural parameters within the enzyme active site
      relevant to enzyme function, especially as they relate to its substrate
      specificity. By docking various disaccharide substrates, we identified potential
      structural determinants present within these substrates that would complement
      this unique active site architecture. These determinants included the position
      and number of sulfates present on the glucosamine, oligosaccharide chain length,
      the presence of a Delta4,5-unsaturated double bond, and the exolytic versus
      endolytic potential of the enzyme. The predictions made from our model provided a
      structural basis of substrate specificity originally interpreted from the
      biochemical and kinetic data. Our modeling approach was further complemented
      experimentally using peptide mapping in tandem with mass spectrometry and site
      directed mutagenesis to physically demonstrate the presence of a covalently
      modified cysteine (formylglycine) within the active site. This combinatorial
      approach of structure modeling and biochemical studies provides insight into the
      molecular basis of enzyme function.

PMID- 12519775
TI  - The heparin/heparan sulfate 2-O-sulfatase from Flavobacterium heparinum.
      Molecular cloning, recombinant expression, and biochemical characterization.
AB  - Heparan sulfate glycosaminoglycans are structurally complex polysaccharides
      critically engaged in a wide range of cell and tissue functions. Any structure
      based approach to study their respective biological functions is facilitated by
      the use of select heparan sulfate glycosaminoglycan-degrading enzymes with unique
      substrate specificities. We recently reported of one such enzyme, the Delta4,5
      glycuronidase cloned from Flavobacterium heparinum and recombinantly expressed in
      Escherichia coli (Myette, J. R., Shriver, Z., Kiziltepe, T., McLean, M. W.,
      Venkataraman, G., and Sasisekharan, R. (2002) Biochemistry 41, 7424-7434). In
      this study, we likewise report the molecular cloning of the 2-O-sulfatase from
      the same bacterium and its recombinant expression as a soluble, highly active
      enzyme. At the protein level, the flavobacterial 2-O-sulfatase possesses
      considerable sequence homology to other members of a large sulfatase family,
      especially within its amino terminus, where the highly conserved sulfatase domain
      is located. Within this domain, we have identified by sequence homology the
      critical active site cysteine predicted to be chemically modified as a
      formylglycine in vivo. We also present a characterization of the biochemical
      properties of the enzyme as it relates to optimal in vitro reaction conditions
      and a kinetic description of its substrate specificity. In particular, we
      demonstrate that in addition to the fact that the enzyme exclusively hydrolyzes
      the sulfate at the 2-O-position of the uronic acid, it also exhibits a kinetic
      preference for highly sulfated glucosamines within each disaccharide unit,
      especially those possessing a 6-O-sulfate. The sulfatase also displays a clear
      kinetic preference for disaccharides with beta1-->4 linkages but is able,
      nevertheless, to hydrolyze unsaturated, 2-O-sulfated chondroitin disaccharides.
      Finally, we describe the substrate-product relationship of the 2-O-sulfatase to
      the Delta4,5-glycuronidase and the analytical value of using both of these
      enzymes in tandem for elucidating heparin/heparan sulfate composition.

PMID- 12519776
TI  - Mouse retinal dehydrogenase 4 (RALDH4), molecular cloning, cellular expression,
      and activity in 9-cis-retinoic acid biosynthesis in intact cells.
AB  - This study describes cDNA cloning and characterization of mouse RALDH4. The 2.3
      kb cDNA encodes an aldehyde dehydrogenase of 487 amino acid residues, about two
      orders of magnitude more active in vitro with 9-cis-retinal than with all-trans
      retinal. RALDH4 recognizes as substrate 9-cis-retinal generated in transfected
      cells by the short-chain dehydrogenases CRAD1, CRAD3, or RDH1, to reconstitute a
      path of 9-cis-retinoic acid biosynthesis in situ. Northern blot analysis showed
      expression of RALDH4 mRNA in adult mouse liver and kidney. In situ hybridization
      revealed expression of RALDH4 in liver on embryo day 14.5, in adult hepatocytes,
      and kidney cortex. Immunohistochemistry confirmed RALDH4 expression in
      hepatocytes and showed that hepatocytes also express RALDH1, RALDH2, and RALDH3.
      Kidney expresses the RALDH4 protein primarily in the proximal and distal
      convoluted tubules of the cortex but not in the glomeruli or the medulla. Kidney
      expresses RALDH2 in the proximal convoluted tubules of the cortex but not in the
      distal convoluted tubules or glomeruli. Kidney expresses RALDH1 and RALDH2 in the
      medulla. The enzymatic characteristics of RALDH4, its expression in fetal liver,
      and its unique expression pattern in adult kidney compared with RALDH1, -2, and 
      3 suggest that it could meet specific needs for 9-cis-retinoic acid biosynthesis.

PMID- 12519777
TI  - Mcp1 encodes the molybdenum cofactor carrier protein in Chlamydomonas reinhardtii
      and participates in protection, binding, and storage functions of the cofactor.
AB  - The molybdenum cofactor (Moco) is essential for the activity of all
      molybdoenzymes except nitrogenase. The cDNA for the Moco carrier protein (MocoCP)
      of Chlamydomonas reinhardtii has been cloned by reverse transcription PCR
      approaches with primers designed from microsequenced peptides of this protein.
      The C. reinhardtii MocoCP has been expressed in Escherichia coli. The recombinant
      protein has been purified to electrophoretic homogeneity and is found assembled
      into a homotetramer when Moco is not present under native conditions. Recombinant
      MocoCP has the same biochemical characteristics as MocoCP from C. reinhardtii, as
      it bound Moco from milk xanthine oxidase with high affinity, prevented Moco
      inactivation by oxygen, and transferred Moco efficiently to aponitrate reductase
      from the Neurospora crassa nit1 mutant. The genomic DNA sequence corresponding to
      the Chlamydomonas MocoCP gene, CrMcp1, also was isolated. This gene contained
      three introns in the coding region. The deduced amino acid sequence of CrMcp1 did
      not show a significant identity to functionally known proteins in the GenBank
      data base, although a significant conservation was found with bacterial proteins
      of unknown function. The results suggest that proteins having a Moco binding
      function probably exist in other organisms.

PMID- 12519778
TI  - Structural and kinetic properties of high and low molecular mass
      phosphoenolpyruvate carboxylase isoforms from the endosperm of developing castor
      oilseeds.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is believed to play an important role in
      producing malate as a substrate for fatty acid synthesis by leucoplasts of the
      developing castor oilseed (COS) endosperm. Two kinetically distinct isoforms of
      COS PEPC were resolved by gel filtration chromatography and purified. PEPC1 is a
      typical 410-kDa homotetramer composed of 107-kDa subunits (p107). In contrast,
      PEPC2 exists as an unusual 681-kDa hetero-octamer composed of the same p107 found
      in PEPC1 and an associated 64-kDa polypeptide (p64) that is structurally and
      immunologically unrelated to p107. Relative to PEPC1, PEPC2 demonstrated
      significantly enhanced thermal stability and a much lower sensitivity to
      allosteric activators (Glc-6-P, Glc-1-P, Fru-6-P, glycerol-3-P) and inhibitors
      (Asp, Glu, malate) and pH changes within the physiological range. Nondenaturing
      PAGE of clarified extracts followed by in-gel PEPC activity staining indicated
      that the ratio of PEPC1:PEPC2 increases during COS development such that only
      PEPC1 is detected in mature COS. Dissimilar developmental profiles and kinetic
      properties support the hypotheses that (i) PEPC1 functions to replenish
      dicarboxylic acids consumed through transamination reactions required for storage
      protein synthesis, whereas (ii) PEPC2 facilitates PEP flux to malate in support
      of fatty acid synthesis. Interestingly, the respective physical and kinetic
      properties of COS PEPC1 and PEPC2 are remarkably comparable with those of the
      homotetrameric low M(r) Class 1 and heteromeric high M(r) Class 2 PEPC isoforms
      of unicellular green algae.

PMID- 12519779
TI  - Phosphorylation of Munc18 by protein kinase C regulates the kinetics of
      exocytosis.
AB  - Protein phosphorylation by protein kinase C (PKC) has been implicated in the
      control of neurotransmitter release and various forms of synaptic plasticity. The
      PKC substrates responsible for phosphorylation-dependent changes in regulated
      exocytosis in vivo have not been identified. Munc18a is essential for
      neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro
      on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in
      response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both
      phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts
      as a phosphomimetic mutation. Unlike phorbol ester treatment, expression of
      Munc18 with this phosphomimetic mutation in PKC phosphorylation sites did not
      affect the number of exocytotic events. The mutant did, however, produce changes
      in single vesicle release kinetics, assayed by amperometry, which were identical
      to those caused by phorbol ester treatment. Furthermore, the effects of phorbol
      ester treatment on release kinetics were occluded in cells expressing
      phosphomimetic Munc18. These results suggest that the dynamics of vesicle release
      events during exocytosis are controlled by PKC directly through phosphorylation
      of Munc18 on Ser-313. Phosphorylation of Munc18 by PKC may provide a mechanism
      for the control of exocytosis and thereby synaptic plasticity.

PMID- 12519780
TI  - Identification of a functional link for the p53 tumor suppressor protein in
      dexamethasone-induced growth suppression.
AB  - Serine/threonine phosphatase 5 (PP5) can act as a suppresser of p53-dependent
      growth suppression and has been reported to associate with several proteins,
      including the glucocorticoid receptor/heat-shock protein-90 complex. Still, the
      physiological/pathological roles of PP5 are unclear. To characterize the
      relationship of PP5, glucocorticoid receptor activation and p53, here we describe
      the development of chimeric antisense oligonucleotides that potently inhibit
      human p53 expression. This allowed us to regulate the expression of either p53
      (e.g. with ISIS 110332) or PP5 (e.g. with ISIS 15534) in genetically identical
      cells. Studies with ISIS 110332 revealed that the suppression of p53 expression
      is associated with a decrease in the basal expression of the cyclin-dependent
      kinase inhibitor protein, p21(WAF1/Cip1), and a concomitant increase in the rate
      of cell proliferation. Suppression of p53 also blocks dexamethasone-induced
      p21(WAF1/Cip1) expression and G(1)-growth arrest. Furthermore, treatment with
      ISIS 110332, but not the mismatched controls, ablates the suppression of growth
      produced by prior treatment with dexamethasone. Additional studies revealed that
      dexamethasone-dependent p21(WAF1/Cip1) expression occurs without an apparent
      change in p53 protein levels or the phosphorylation status of p53 at Ser-6, -37,
      or -392. However, dexamethasone treatment is associated with an increase in p53
      phosphorylation at Ser-15. Suppression of PP5 expression with ISIS 15534 also
      results in the hyperphosphorylation of p53 at Ser-15. Together, these findings
      indicate that the basal expression of p53 plays a functional role in a
      glucocorticoid receptor-mediated response regulating the expression of
      p21(Waf1/Cip1) via a mechanism that is suppressed by PP5 and associated with the
      phosphorylation of p53 at Ser-15.

PMID- 12519781
TI  - The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast
      growth factor 23 resists proteolytic cleavage and enhances in vivo biological
      potency.
AB  - Missense mutations in fibroblast growth factor 23 (FGF23) are the cause of
      autosomal dominant hypophosphatemic rickets (ADHR). The mutations (R176Q, R179W,
      and R179Q) replace Arg residues within a subtilisin-like proprotein convertase
      (SPC) cleavage site (RXXR motif), leading to protease resistance of FGF23. The
      goals of this study were to examine in vivo the biological potency of the R176Q
      mutant FGF23 form and to characterize alterations in homeostatic mechanisms that
      give rise to the phenotypic presentation of this disorder. For this, wild type
      and R176Q mutant FGF23 were overexpressed in the intact animals using a tumor
      bearing nude mouse system. At comparable circulating levels, the mutant form was
      more potent in inducing hypophosphatemia, in decreasing circulating
      concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and in causing
      rickets and osteomalacia in these animals compared with wild type FGF23.
      Parameters of calcium homeostasis were also altered, leading to secondary
      hyperparathyroidism and parathyroid gland hyperplasia. However, the raised
      circulating levels of parathyroid hormone were ineffective in normalizing the
      reduced 1,25(OH)(2)D(3) levels by increasing renal expression of 25(OH)D(3)
      1alpha-hydroxylase (Cyp40) to promote its synthesis and by decreasing that of
      25(OH)D(3)-24-hydroxylase (Cyp24) to prevent its catabolism. The findings provide
      direct in vivo evidence that missense mutations from ADHR kindreds are gain-of
      function mutations that retain and increase the protein's biological potency.
      Moreover, for the first time, they define a potential role for FGF23 in
      dissociating parathyroid hormone actions on mineral fluxes and on vitamin D
      metabolism at the level of the kidney.

PMID- 12519782
TI  - Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP)
      interacts with and stimulates its associated DNA-dependent protein kinase.
AB  - Nuclear receptors mediate gene activation through ligand-dependent interaction
      with coactivators. We previously cloned and characterized thyroid hormone
      receptor-binding protein, TRBP (NcoA6: AIB3/ASC-2/RAP250/PRIP/TRBP/NRC), as an
      LXXLL-containing coactivator that associates with coactivator complexes through
      its C terminus. To search for protein factors involved in TRBP action, we
      identified a distinct set of proteins from HeLa nuclear extract that interacts
      with the C terminus of TRBP. Analysis by mass spectrometric protein sequencing
      revealed a DNA-dependent protein kinase (DNA-PK) complex including its catalytic
      subunit and regulatory subunits, Ku70 and Ku86. DNA-PK is a heterotrimeric
      nuclear phosphatidylinositol 3-kinase that functions in DNA repair,
      recombination, and transcriptional regulation. DNA-PK phosphorylates TRBP at its
      C-terminal region, which directly interacts with Ku70 but not Ku86 in vitro. In
      addition, in the absence of DNA, TRBP itself activates DNA-PK, and the TRBP
      stimulated DNA-PK activity has an altered phosphorylation pattern from DNA
      stimulated activity. An anti-TRBP antibody inhibits TRBP-induced kinase activity,
      suggesting that protein content of TRBP is responsible for the stimulation of DNA
      independent kinase activity. Furthermore, in DNA-PK-deficient scid cells, TRBP
      mediated transactivation is significantly impaired, and nuclear localization of
      TRBP is altered. The activation of DNA-PK in the absence of DNA ends by the
      coactivator TRBP suggests a novel mechanism of coactivator-stimulated DNA-PK
      phosphorylation in transcriptional regulation.

PMID- 12519783
TI  - Alterations in the expression of transcription factors and the reduced folate
      carrier as a novel mechanism of antifolate resistance in human leukemia cells.
AB  - The human reduced folate carrier (hRFC) is the dominant transporter mediating the
      uptake of reduced folate cofactors and antifolate anticancer drugs. Defective
      antifolate uptake due to inactivating mutations in the hRFC gene is an
      established mechanism of drug resistance in various tumor cells. However, while
      antifolate transport is frequently impaired, either no or only a single hRFC
      allele is inactivated, suggesting that additional mechanism(s) of resistance are
      operative. Here we studied the relationship between the expression and function
      of transcription factors and antifolate resistance in transport-defective
      leukemia cells that poorly express or completely lack RFC mRNA. Stable
      transfection with a hRFC expression construct resulted in restoration of normal
      RFC mRNA expression and nearly wild type drug sensitivity in these antifolate
      resistant cells. The loss of RFC gene expression prompted us to explore
      transcription factor binding to the hRFC promoter. The hRFC promoter contains an
      upstream GC-box and a downstream cAMP-response element (CRE)/AP-1-like element.
      Electrophoretic mobility shift assays and oligonucleotide competition revealed a
      substantial loss of nuclear factor binding to CRE and GC-box in these drug
      resistant cell lines. Consistently, antibody-mediated supershift analysis showed
      a marked decrease in the binding of CRE-binding protein 1 (CREB-1) and
      specificity protein 1 (Sp1) to CRE and GC-box, respectively. Western blot
      analysis revealed undetectable expression of CREB-1, decreased ATF-1 levels,
      parental Sp1 levels, and increased levels of the short Sp3 isoforms, recently
      shown to repress hRFC gene expression. Transient transfections into these
      antifolate-resistant cells demonstrated a marked loss of GC-box-dependent, and
      CRE-driven reporter gene activities and introduction of CREB-1 or Sp1 expression
      constructs resulted in restoration of hRFC mRNA expression. These results
      establish a novel mechanism of antifolate resistance that is based on altered
      expression and function of transcription factors resulting in transcriptional
      silencing of the hRFC promoter.

PMID- 12519784
TI  - Onset of carbon catabolite repression in Aspergillus nidulans. Parallel
      involvement of hexokinase and glucokinase in sugar signaling.
AB  - The role of hexose phosphorylating enzymes in the signaling of carbon catabolite
      repression was investigated in the filamentous fungus Aspergillus nidulans. A d
      fructose non-utilizing, hexokinase-deficient (hxkA1, formerly designated frA1)
      strain was utilized to obtain new mutants lacking either glucokinase (glkA4) or
      both hexose kinases (hxkA1/glkA4). d-Glucose and d-fructose phosphorylation is
      completely abolished in the double mutant, which consequently cannot grow on
      either sugar. The glucokinase single mutant exhibits no nutritional deficiencies.
      Three repressible diagnostic systems, ethanol utilization (alcA and alcR genes),
      xylan degradation (xlnA), and acetate catabolism (facA), were analyzed in these
      hexose kinase mutants at the transcript level. Transcriptional repression by d
      glucose is fully retained in the two single kinase mutants, whereas the
      hexokinase mutant is partially derepressed for d-fructose. Thus, hexokinase A and
      glucokinase A compensate each other for carbon catabolite repression by d-glucose
      in the single mutants. In contrast, both d-glucose and d-fructose repression are
      severely impaired for all three diagnostic systems in the double mutant. Unlike
      the situation in Saccharomyces cerevisiae, the hexose phosphorylating enzymes
      play parallel roles in glucose repression in A. nidulans.

PMID- 12519785
TI  - Lowered temperature set point for activation of the cellular stress response in T
      lymphocytes.
AB  - The induction of heat shock protein gene expression in response to stress is
      critical for the ability of organisms to cope with and survive exposure to these
      stresses. However, most studies on HSF1-mediated induction of hsp70 gene
      expression have utilized immortalized cell lines and temperatures above the
      physiologically relevant range. For these reasons much less is known about the
      heat shock response as it occurs in mammalian cells within tissues in the intact
      organism. To gain insight into this area we determined the temperature thresholds
      for activation of HSF1 DNA binding in different mouse tissues. We have found that
      HSF1 DNA binding activity and hsp70 synthesis are induced in spleen cells at
      significantly lower temperatures relative to cells of other tissues, with a
      temperature threshold for activation (39 degrees C) that is within the
      physiological range for fever. Furthermore, we found that the lowered temperature
      set point for induction of the stress response in spleen is specific to T
      lymphocytes residing within this tissue and is not exhibited by B-lymphocytes.
      This lowered threshold is also observed in T-lymphocytes isolated from lymph
      nodes, suggesting that it is a general property of T-lymphocytes, and is seen in
      different mouse strains. Fever is an early event in the immune response to
      infection, and thus activation of the cellular stress response in T-lymphocytes
      by fever temperatures could serve as a way to give these cells enough time to
      express hsps in anticipation of their function in the coming immune response. The
      induced hsps likely protect these cells from the stressful conditions that can
      exist during the immune response, for example increasing their protection against
      stress-induced apoptosis.

PMID- 12519786
TI  - Exposure of single-stranded telomeric DNA causes G2/M cell cycle arrest in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, Cdc13p is a single-stranded TG(1-3) DNA binding
      protein that protects telomeres and maintains telomere length. A mutant allele of
      CDC13, cdc13-1, causes accumulation of single-stranded TG(1-3) DNA near telomeres
      along with a G(2)/M cell cycle arrest at non-permissive temperatures. We report
      here that when the single-stranded TG(1-3) DNA is masked by its binding proteins,
      such as S. cerevisiae Gbp2p or Schizosaccharomyces pombe Tcg1, the growth arrest
      phenotype of cdc13-1 is rescued. Mutations on Gbp2p that disrupt its binding to
      the single-stranded TG(1-3) DNA render the protein unable to complement the
      defects of cdc13-1. These results indicate that the presence of a single-stranded
      TG(1-3) tail in cdc13-1 cells serves as the signal for the cell cycle checkpoint.
      Moreover, the binding activity of Gbp2p to single-stranded TG(1-3) DNA appears to
      be associated with its ability to restore the telomere-lengthening phenotype in
      cdc13-1 cells. These results indicate that Gbp2p is involved in modulating
      telomere length.

PMID- 12519787
TI  - Retinoid X receptor (RXR) agonist-induced antagonism of farnesoid X receptor
      (FXR) activity due to absence of coactivator recruitment and decreased DNA
      binding.
AB  - The bile salt export pump (BSEP) plays an integral role in lipid homeostasis by
      regulating the canalicular excretion of bile acids. Induction of BSEP gene
      expression is mediated by the farnesoid X receptor (FXR), which binds as a
      heterodimer with the retinoid X receptor (RXR) to the FXR response element (FXRE)
      located upstream of the BSEP gene. RXR ligands mimic several partner ligands and
      show additive effects upon coadministration. Using real-time quantitative PCR and
      cotransfection reporter assays, we demonstrate that the RXR agonist LG100268
      antagonizes induction of BSEP expression mediated by endogenous and synthetic FXR
      ligands, CDCA and GW4064, respectively. Moreover, this antagonism is a general
      feature of RXR agonists and is attributed to a decrease in binding of FXR/RXR
      heterodimers to the BSEP-FXRE coupled with the inability of RXR agonists to
      recruit coactivators to FXR/RXR. Our data suggest that FXR/RXR is a conditionally
      permissive heterodimer and is the first example of RXR ligand-mediated antagonism
      of FXR activity. Because FXR agonists lower triglyceride levels, our results
      suggest a novel role for RXR-mediated antagonism of FXR activity in the
      development of hypertriglyceridemia observed with RXR agonists in rodents and
      humans.

PMID- 12519788
TI  - Change of conformation of the DNA-binding domain of p53 is the only key element
      for binding of and interference with p73.
AB  - Xenopus p53 has biological and biochemical properties similar to those of human
      p53, except for optimal temperature. The frog protein is fully active at 30
      degrees C and inactive at 37 degrees C, leading to a temperature-sensitive
      behavior similar to that of the human mutant p53Ala(143) and the murine mutant
      p53Val(135). Using hybrid proteins between human and Xenopus expressed from
      artificial p53 minigenes, we have been able to demonstrate that change of
      conformation of the DNA-binding domain is the major determinant of this heat
      sensitivity. It has been reported that some human tumor-derived p53 mutants can
      engage in a physical association with p73, thus inhibiting its transactivating
      properties. The mechanism of this association remains to be elucidated. The
      nature of the mutant p53 that can engage in this association also remains
      controversial. Using the unique opportunity of the temperature sensitivity of
      Xenopus p53, we demonstrate that binding of and interference with p73 require a
      change of conformation in the p53 protein. This interaction occurs through the
      DNA-binding domain of p53 only when it is in a denatured state. These results
      reinforce the notion that mutant p53 with a conformational change can act as a
      down-regulator of the p73 pathway in human cancer and could confer a selective
      advantage to the tumor.

PMID- 12519789
TI  - Proteomic and biochemical analyses of human B cell-derived exosomes. Potential
      implications for their function and multivesicular body formation.
AB  - Exosomes are 60-100-nm membrane vesicles that are secreted into the extracellular
      milieu as a consequence of multivesicular body fusion with the plasma membrane.
      Here we determined the protein and lipid compositions of highly purified human B
      cell-derived exosomes. Mass spectrometric analysis indicated the abundant
      presence of major histocompatibility complex (MHC) class I and class II, heat
      shock cognate 70, heat shock protein 90, integrin alpha 4, CD45, moesin, tubulin
      (alpha and beta), actin, G(i)alpha(2), and a multitude of other proteins. An
      alpha 4-integrin may direct B cell-derived exosomes to follicular dendritic
      cells, which were described previously as potential target cells. Clathrin, heat
      shock cognate 70, and heat shock protein 90 may be involved in protein sorting at
      multivesicular bodies. Exosomes were also enriched in cholesterol, sphingomyelin,
      and ganglioside GM3, lipids that are typically enriched in detergent-resistant
      membranes. Most exosome-associated proteins, including MHC class II and
      tetraspanins, were insoluble in 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonic acid (CHAPS)-containing buffers. Multivesicular body-linked MHC
      class II was also resistant to CHAPS whereas plasma membrane-associated MHC class
      II was solubilized readily. Together, these data suggest that recruitment of
      membrane proteins from the limiting membranes into the internal vesicles of
      multivesicular bodies may involve their incorporation into tetraspanin-containing
      detergent-resistant membrane domains.

PMID- 12519790
TI  - ADP-ribosylation factor-dependent phospholipase D2 activation is required for
      agonist-induced mu-opioid receptor endocytosis.
AB  - Agonist exposure of many G protein-coupled receptors induces a rapid receptor
      phosphorylation and uncoupling from G proteins. Resensitization of these
      desensitized receptors requires endocytosis and subsequent dephosphorylation.
      Using a yeast two-hybrid screen, the rat mu-opioid receptor (MOR1, also termed
      MOP) was found to be associated with phospholipase D2 (PLD2), a phospholipid
      specific phosphodiesterase located in the plasma membrane, which has been
      implicated in the formation of endocytotic vesicles. Coimmunoprecipitation
      experiments in HEK293 cells coexpressing MOR1 and PLD2 confirmed that MOR1
      constitutively interacts with PLD2. Treatment with the mu receptor agonist DAMGO
      ([d-Ala(2), Me Phe(4), Glyol(5)]enkephalin) led to an increase in PLD2 activity,
      whereas morphine, which does not induce MOR1 receptor internalization, failed to
      induce PLD2 activation. The DAMGO-mediated PLD2 activation was inhibited by
      brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) but not by the protein
      kinase C (PKC) inhibitor calphostin C indicating that opioid receptor-mediated
      activation of PLD2 is ARF- but not PKC-dependent. Furthermore, heterologous
      stimulation of PLD2 by phorbol ester led to an accelerated internalization of the
      mu-opioid receptor after both DAMGO and morphine exposure. Conversely the
      inhibition of PLD2-mediated phosphatidic acid formation by 1-butanol or
      overexpression of a negative mutant of PLD2 prevented agonist-mediated
      endocytosis of MOR1. Together, these data suggest that PLD2 play a key role in
      the regulation of agonist-induced endocytosis of the mu-opioid receptor.

PMID- 12519792
TI  - Hepatocyte nuclear factor-4 is a novel downstream target of insulin via FKHR as a
      signal-regulated transcriptional inhibitor.
AB  - Previous studies have shown that FKHR, a member of the forkhead family of
      transcription factors, acts as a DNA binding-independent cofactor of nuclear
      receptors, including estrogen, retinoid, and thyroid hormone receptors, in
      addition to the original function as a DNA binding transcription factor that
      redistributes from the nucleus to the cytoplasm by insulin-induced
      phosphorylation. Here, we demonstrated the physical interaction of FKHR with
      hepatocyte nuclear factor (HNF)-4, a member of steroid/thyroid nuclear receptor
      superfamily, and the repression of HNF-4 transactivation by FKHR. FKHR interacted
      with the DNA binding domain of HNF-4 and inhibited HNF-4 binding to the cognate
      DNA. Furthermore, the binding affinity of HNF-4 with phosphorylated FKHR
      significantly decreased in comparison to that with unphosphorylated FKHR.
      Therefore, a phosphorylation of FKHR by insulin followed by its dissociation from
      HNF-4 and the redistribution of FKHR from the nucleus to the cytoplasm would
      expect to induce the transcriptional activation of HNF-4 by facilitating to the
      access of HNF-4 to its DNA element. Indeed, most intriguingly, insulin
      stimulation reversed the repression of HNF-4 transcriptional activity by
      phosphorylation-sensitive (wild-type) FKHR, but not by phosphorylation-deficient
      FKHR. These results suggest that insulin regulates the transcriptional activity
      of HNF-4 via FKHR as a signal-regulated transcriptional inhibitor.

PMID- 12519791
TI  - Role of G protein-coupled receptor kinase 4 and beta-arrestin 1 in agonist
      stimulated metabotropic glutamate receptor 1 internalization and activation of
      mitogen-activated protein kinases.
AB  - The metabotropic glutamate 1 (mGlu(1)) receptor in cerebellar Purkinje cells
      plays a key role in motor learning and motor coordination. Here we show that the
      G protein-coupled receptor kinases (GRK) 2 and 4, which are expressed in these
      cells, regulate the mGlu(1) receptor by at least in part different mechanisms.
      Using kinase-dead mutants in HEK293 cells, we found that GRK4, but not GRK2,
      needs the intact kinase activity to desensitize the mGlu(1) receptor, whereas
      GRK2, but not GRK4, can interact with and regulate directly the activated
      Galpha(q). In cells transfected with GRK4 and exposed to agonist, beta-arrestin
      was first recruited to plasma membranes, where it was co-localized with the
      mGlu(1) receptor, and then internalized in vesicles. The receptor was also
      internalized but in different vesicles. The expression of beta-arrestin V53D
      dominant negative mutant, which did not affect the mGlu(1) receptor
      internalization, reduced by 70-80% the stimulation of mitogen-activated protein
      (MAP) kinase activation by the mGlu(1) receptor. The agonist-stimulated
      differential sorting of the mGlu(1) receptor and beta-arrestin as well as the
      activation of MAP kinases by mGlu(1) agonist was confirmed in cultured cerebellar
      Purkinje cells. A major involvement of GRK4 and of beta-arrestin in agonist
      dependent receptor internalization and MAP kinase activation, respectively, was
      documented in cerebellar Purkinje cells using an antisense treatment to knock
      down GRK4 and expressing beta-arrestin V53D dominant negative mutant by an
      adenovirus vector. We conclude that GRK2 and GRK4 regulate the mGlu(1) receptor
      by different mechanisms and that beta-arrestin is directly involved in glutamate
      stimulated MAP kinase activation by acting as a signaling molecule.

PMID- 12519793
TI  - After Nice: where now for health policy in the European Union?

PMID- 12519794
TI  - Update on squint and amblyopia.

PMID- 12519795
TI  - Hearing loss in motorcyclists: occupational and medicolegal aspects.

PMID- 12519796
TI  - Symptom severity in advanced cancer, assessed in two ethnic groups by interviews
      with bereaved family members and friends.
AB  - Little research has been reported on the experience of cancer among minority
      ethnic communities in the UK. As part of a wider survey in inner London we
      interviewed bereaved family members or close friends of 34 first-generation black
      Caribbeans and of 35 UK-born white patients about symptoms and symptom control in
      the year before death with cancer. They were drawn from population samples in
      which the response rates were equal at about 46%. Symptoms in the two ethnic
      groups were similar. However, multivariate logistic regression indicated greater
      symptom-related distress in black Caribbeans for appetite loss, pain, dry mouth,
      vomiting and nausea, and mental confusion. Respondents were also more likely to
      say, in relation to black Caribbean patients, that general practitioners (though
      not hospital doctors) could have tried harder to manage symptoms. The findings
      suggest a need for better assessment and management of cancer symptoms in first
      generation Caribbean Londoners, guided by a deeper understanding of cultural
      influences on their responses to advanced illness.

PMID- 12519798
TI  - Babington's aphasia-overcoming left hemisphere trauma.

PMID- 12519797
TI  - How objective are systematic reviews? Differences between reviews on
      complementary medicine.
AB  - Systematic reviews are considered the most reliable tool to summarize existing
      evidence. To determine whether reviews that address the same questions can
      produce different answers we examined systematic reviews of herbal medicine,
      homeopathy, and acupuncture taken from a previously established database.
      Information on literature searching, inclusion criteria, selection process,
      quality assessment, data extraction, methods to summarize primary studies, number
      of included studies, results and conclusions was compared qualitatively.
      Seventeen topics (eight on acupuncture, six on herbal medicines, three on
      homeopathy) had been addressed by 2-5 systematic reviews each. The number of
      primary studies in the reviews varied greatly within most topics. The most
      obvious reason for discrepancies between the samples was different inclusion
      criteria (in thirteen topics). Methods of literature searching may have
      contributed with some topics but the equivalence of the searches was difficult to
      assess. Differences were frequently observed in other methodological aspects, in
      results and in conclusions. This analysis shows that, at least in the three areas
      examined, systematic reviews often differ considerably. Readers should be aware
      that apparently minor decisions in the review process can have major impact.

PMID- 12519799
TI  - Visual field compression by a non-secreting pituitary tumour during pregnancy.

PMID- 12519800
TI  - Mesh repair of sacral hernia following sacrectomy.

PMID- 12519801
TI  - Phacomatosis pigmentokeratotica.

PMID- 12519802
TI  - Antibiotic-resistant cellulitis acquired in Turkey.

PMID- 12519803
TI  - Mixed blessings: ethical issues in assisted conception.

PMID- 12519805
TI  - Singular scientists.

PMID- 12519806
TI  - Philosophy for physicians.

PMID- 12519808
TI  - Triggering of thyroid hormone autoantibodies.

PMID- 12519809
TI  - Anonymized dysgraphia.

PMID- 12519810
TI  - Hereditary somnambulism in Dracula.

PMID- 12519811
TI  - Illegible handwriting in medical records.

PMID- 12519812
TI  - Diabetes in Ramadan.

PMID- 12519813
TI  - Consent for autopsy.

PMID- 12519814
TI  - William Budd and typhoid fever.

PMID- 12519815
TI  - HIV in Africa.

PMID- 12519817
TI  - William Budd and typhoid fever.

PMID- 12519819
TI  - Pharmacologic approaches to the prevention of type 2 diabetes in high risk
      pediatric patients.

PMID- 12519820
TI  - Reduced metabolic rate after caloric restriction-can we agree on how to normalize
      the data?

PMID- 12519821
TI  - Energy expenditure of rhesus monkeys subjected to 11 years of dietary
      restriction.
AB  - Dietary restriction (DR) is currently the only paradigm that has consistently
      extended maximal life span and reduced the onset of age-related chronic diseases
      in all of the nonprimate species tested. Although it is controversial, some
      investigators have suggested that the underlying mechanisms may be mediated by
      adaptations in energy expenditure. We evaluated the extent to which DR alters
      energy metabolism in a unique cohort of rhesus monkeys submitted to DR for 11 yr.
      Total energy expenditure (doubly labeled water), resting energy expenditure (REE;
      indirect calorimetry), and nonbasal energy expenditure (calculated by difference)
      were measured in DR (n = 12) and control (n = 11) animals. Body composition was
      determined by dual energy x-ray absorptiometry. Both fat mass and fat-free mass
      were lower in the restricted animals (56 and 12%, respectively). DR induced a 17%
      lower total energy expenditure that was attributable to a 20% decrease in REE
      without changes in the nonbasal energy expenditure. Adjusted for fat-free mass,
      REE was 13% lower with DR (-250 kJ/d). Taken together with a reanalysis of
      previous DR experiments published in humans, rodents, and monkeys, these results
      suggest that DR may lower REE independent of the DR-induced changes in body
      composition. Whether this reduction in REE contributes to the life-extending
      properties of DR warrants further analysis, but it suggests that the long
      standing debate regarding DR effects on metabolic rates may derive from the lack
      of consensus on how to adjust for body size and composition.

PMID- 12519822
TI  - Time to wake-up to the individual variation in sleep needs.

PMID- 12519823
TI  - A longer biological night in long sleepers than in short sleepers.
AB  - Habitual sleep duration varies greatly among individuals. The physiological basis
      of this variation is unknown. We sought to determine whether individual
      differences in sleep duration are associated with systematic differences in the
      duration of the biological night that is programmed by the circadian pacemaker
      and reflected in the nocturnal interval of circadian rhythms in neuroendocrine
      function, body temperature, and arousal. Ten young, healthy long sleepers (sleep
      duration >9 h) and 14 short sleepers (<6 h) were studied under constant
      environmental conditions and in the absence of sleep. The nocturnal intervals of
      high plasma melatonin levels, increasing cortisol levels, low body temperature,
      and increasing sleepiness were longer in long sleepers than in short sleepers.
      The maxima in cortisol and sleepiness exhibited a close relationship to habitual
      wake-up time, which occurred approximately 2.5 h later in long sleepers than in
      short sleepers. It is concluded that the circadian pacemaker programs a longer
      biological night in long sleepers than in short sleepers. We propose that
      individual differences in the circadian pacemaker's program may contribute to the
      variability of sleep duration in the general population. The persistence or
      inertia of an individual's circadian program, as was evident in constant
      conditions, may underlie the commonly experienced difficulty of changing habitual
      sleep duration willfully.

PMID- 12519824
TI  - Cushing's disease, 70 years later. and the beat goes on.

PMID- 12519825
TI  - Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's
      disease: an effective second-line treatment.
AB  - Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's
      disease (CD). Options for treatment of postoperative persisting hypercortisolemia
      are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From
      1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All
      underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven
      (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative
      period (2-20 d), indicating lack of cure. These patients (6 males and 1 female;
      mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received
      external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a
      dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective,
      hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4)
      and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane,
      3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval
      from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr
      (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300
      nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty
      occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH
      secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH
      deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and
      received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr
      post RT in two patients showed normal gonadotropin secretion and recovery of GH
      peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr
      (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT
      is an effective and relatively rapid-onset treatment for pediatric CD after
      failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up
      suggests some recovery of GH secretion and preservation of other anterior
      pituitary function.

PMID- 12519826
TI  - Familial combined pituitary hormone deficiency due to a novel mutation R99Q in
      the hot spot region of Prophet of Pit-1 presenting as constitutional growth
      delay.
AB  - Combined pituitary hormone deficiency (CPHD) is characterized by impaired
      production of GH and one or more of the other anterior pituitary hormones.
      Prophet of Pit-1 (PROP-1), one of the pituitary specific homeodomain
      transcription factors, is involved in the differentiation of the anterior
      pituitary cells (somatotrophs, lactotrophs, thyrotrophs, and gonadotrophs), and
      PROP-1 gene mutations may interfere with the development of these cells,
      resulting in CPHD. We performed molecular analyses of the PROP-1 gene in two
      siblings, born to consanguineous parents, who presented with short stature. The
      index patient, a boy, was initially diagnosed with constitutional growth delay
      based on familial short stature, low parental target height, normal GH secretion,
      and imaging of the pituitary gland. On follow-up, auxological data and pubertal
      delay prompted a thorough reevaluation, which documented GH, TSH, and
      gonadotropin deficiencies. Direct sequencing of the PROP-1 gene revealed a novel
      homozygous transition 296G-->A in exon 2 in the two affected siblings. The
      mutation substitutes a highly conserved arginine by a glutamine at codon 99
      (R99Q) in the second helix of the DNA-binding domain of the PROP-1 protein.
      Compared with wild-type PROP-1, R99Q displays a significant decrease in DNA
      binding on a paired box response element (PRDQ9) and trans-activation of a
      luciferase reporter gene. The findings emphasize the importance of repeated
      evaluations and illustrate that patients with CPHD associated with PROP-1
      mutations present with a phenotypic spectrum, suggesting that the consequences of
      distinct PROP-1 mutations may be diverse and/or that additional factors, such as
      modifier genes, may have an impact on their expressivity.

PMID- 12519827
TI  - Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic
      nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient.
AB  - HESX1/Hesx1 is a member of the paired-like class of homeobox genes and is
      essential for pituitary and forebrain development. Mice with a targeted
      homozygous deletion of the Hesx1 show severe central nervous system defects,
      absence of optic vesicles, and a very small anterior pituitary gland. This
      phenotype is similar to the abnormalities observed in the human disorder called
      septo-optic dysplasia, a syndromic form of congenital hypopituitarism. To date,
      four missense mutations in the human HESX1 have been described in individuals
      with phenotypes ranging from severe septo-optic dysplasia, relatively mild
      combined pituitary hormone deficiency (CPHD), to isolated GH deficiency. Here we
      report a Japanese patient with CPHD (GH, TSH, LH, FSH, and ACTH deficiency) due
      to a novel sporadic HESX1 mutation. Brain magnetic resonance imaging examination
      revealed hypoplastic anterior pituitary, ectopic posterior lobe, and left optic
      nerve hypoplasia. Molecular analysis identified the insertion of a heterozygous
      mutation (306/307ins AG) in the exon 2 of the HESX1. This mutation changes a
      reading frame and introduces a premature stop codon soon after the mutation site.
      Therefore, this mutation would be predicted to generate a protein lacking the
      carboxyl-terminal homebox domain (DNA-binding domain) and cause the disease.
      Family analysis demonstrated that neither of the patient's parents harbored this
      mutation, indicating that the mutation had arisen de novo. In conclusion, a de
      novo heterozygous frameshift mutation in exon 2 of the HESX1 causes severe CPHD
      with optic nerve hypoplasia in a human.

PMID- 12519829
TI  - Central diabetes insipidus due to cytomegalovirus infection of the hypothalamus
      in a patient with acquired immunodeficiency syndrome: a clinical, pathological,
      and immunohistochemical case study.
AB  - We report a case of central diabetes insipidus (CDI) in a patient with AIDS due
      to cytomegalovirus (CMV) infection of the vasopressin-producing areas of the
      hypothalamus. The clinical diagnosis is established by definitive clinical and
      laboratory evidence of CDI. Detailed histopathological and immunohistochemical
      studies establish CMV as the causative agent and demonstrate the deficit of
      vasopressin in the synthesizing neurons. Physicians caring for patients with AIDS
      should be aware of CDI and adipsic hypernatremia as potential complications of
      CMV infection. The case also demonstrates that patients with diabetes insipidus
      do not have polyuria when glucocorticoid deficiency coexists.

PMID- 12519830
TI  - Peroxisome proliferator-activated receptor-gamma in thyroid eye disease:
      contraindication for thiazolidinedione use?
AB  - A male type-2 diabetic, treated with the peroxisome proliferator-activated
      receptor (PPAR) agonist, Pioglitazone, experienced exacerbation of his thyroid
      eye disease (TED), which had been stable and inactive for more then 2 yr.
      Expansion of the orbital fat developed, and we have investigated the effects of
      PPAR gamma agonists, including Pioglitazone and, subsequently, an antagonist on
      the adipogenesis of preadipocytes from TED orbits and Graves' neck fats. The
      percentage of differentiating cells, assessed by oil red O staining,
      morphological changes, and PPAR gamma transcript levels, was determined for
      preadipocytes in hormone/agonist-induced models of adipogenesis, supplemented or
      not with PPAR gamma agonists or antagonist. The PPAR gamma agonists resulted in a
      2- to 13-fold increase, and a PPAR gamma antagonist produced a 2- to 7-fold
      reduction in adipogenesis in vitro. Effects were dose dependent and maximal at 1
      or 10 micro M. We suggest that care should be exercised when selecting patients
      for treatment with PPAR gamma agonists and that such agonists may be
      contraindicated in individuals with a previous history of autoimmune thyroid or
      eye diseases. Our work also suggests that PPAR gamma antagonists could provide a
      novel therapy for TED patients in the active stage of disease.

PMID- 12519831
TI  - A syndrome of hypocalciuric hypercalcemia caused by autoantibodies directed at
      the calcium-sensing receptor.
AB  - Antibodies to cell surface receptors can cause endocrine dysfunction by mimicking
      or blocking the actions of their respective hormones. We sought patients with
      autoantibodies to the extracellular calcium (Ca(2+)(o))-sensing receptor (CaR),
      which sets the normal level of blood calcium, that mimic the genetic disorder,
      familial hypocalciuric hypercalcemia, caused by heterozygous inactivating
      mutations of the CaR. Four individuals from two kindreds were identified with PTH
      dependent hypercalcemia, who had other autoimmune manifestations: one with sprue
      and antigliadin and antiendomyseal antibodies and three with antithyroid
      antibodies. Three of the patients also had relative or absolute hypocalciuria.
      The patients' sera contained antibodies that reacted with the cell surface of
      bovine parathyroid cells in a manner similar to an authentic polyclonal anti-CaR
      antibody, stained bands on Western analysis of sizes similar to those labeled by
      the anti-CaR antiserum, and reacted with several synthetic peptides derived from
      sequences within the CaR's extracellular amino terminus. The patients' sera also
      stimulated PTH release from dispersed human parathyroid cells compared with the
      effect of sera from normocalcemic control subjects. This stimulation could be
      blocked by preabsorbing serum with membranes from CaR-transfected, but not
      nontransfected, human embryonic kidney (HEK293) cells. Finally, in two of the
      patients, antibodies affinity-purified using a synthetic peptide from within the
      CaR's extracellular domain inhibited high Ca(2+)(o)-stimulated, CaR-mediated
      accumulation of inositol phosphates and activation of mitogen-activated protein
      kinase in CaR-transfected HEK293 cells. DNA sequencing revealed no mutations
      within the index patients' CaR genes in the two families. Therefore, a
      biochemical phenotype of PTH-dependent hypercalcemia resembling that caused by
      heterozygous inactivating mutations of the CaR in familial hypocalciuric
      hypercalcemia can be observed in patients with antibodies to the CaR's
      extracellular domain that stimulate PTH release, probably by inhibiting
      activation of the CaR by Ca(2+)(o). Autoimmune hypocalciuric hypercalcemic is an
      acquired disorder of Ca(2+)(o) sensing that should be differentiated from that
      caused by inactivating mutations of the CaR.

PMID- 12519832
TI  - Virilization in bilateral macronodular adrenal hyperplasia controlled by
      luteinizing hormone.
AB  - We report a case of a virilized 59-yr-old woman with elevated serum testosterone
      levels and bilateral macronodular adrenal hyperplasia. The patient underwent
      laparoscopic right adrenalectomy, after which the elevated testosterone level
      transiently normalized. The immediate postoperative depression of the
      testosterone level suggested that the process was driven by gonadotropins that
      were suppressed by the stress of surgery. The excised right adrenal mass
      contained testosterone by immunohistochemistry and LH receptor mRNA by in situ
      hybridization. The recurrence of hyperandrogenemia suggested that the enlarged
      left adrenal was also secreting testosterone. The serum testosterone level
      increased in response to im injection of human chorionic gonadotropin, suggesting
      control by aberrant LH receptors. Injection of leuprolide acetate (7.5 mg im) to
      suppress LH levels resulted in normalization of the testosterone level 12 d later
      that persisted for several weeks. Ectopic receptors mediating Cushing's syndrome
      have been described in several cases of bilateral adrenal hyperplasia and adrenal
      adenoma. This is the first case to our knowledge in which pure androgen
      overproduction in adrenal hyperplasia has been shown to be controlled by LH
      receptors. In our patient, the control of androgen secretion by LH may explain
      the postmenopausal onset of virilization and the transient postoperative
      normalization of the serum testosterone level.

PMID- 12519833
TI  - A randomized controlled trial of estrogen replacement therapy in long-term users
      of depot medroxyprogesterone acetate.
AB  - Long-term use of the injectable contraceptive depot medroxyprogesterone acetate
      (DMPA, Depo-Provera) is associated with a reduction in bone mineral density
      (BMD), particularly in the lumbar spine. The cause of DMPA-associated bone loss
      is not known, but the relative estrogen deficiency induced by DMPA use could be
      responsible. We have undertaken a randomized, double-blind controlled trial of
      oral estrogen replacement therapy in 38 premenopausal women (mean age 37) with a
      minimum 2 yr DMPA use who had a below average baseline lumbar spine BMD (T score
      < or = 0). Nineteen women were allocated to receive conjugated estrogens (0.625
      mg/d orally) and 19 to receive a matching placebo. All continued with regular
      DMPA injections throughout the study. Areal bone density was measured by dual
      energy x-ray absorptiometry at the lumbar spine, femoral neck, and total body
      sites every 6 months for 2 yr; the main outcome measure being the change in areal
      BMD at the lumbar spine. At baseline, the two groups were well matched for
      demographic, anthropometric, and biochemical variables, and for BMD. Twenty-seven
      subjects completed at least 18 months in the study, and 26 the full 2 yr, with
      similar numbers dropping out from each group (mainly for personal reasons). In
      the estrogen-treated group, mean lumbar spine BMD increased 1%, whereas in the
      placebo group it fell 2.6%, over 2 yr. The between group differences were 2.0% at
      12 months (P = 0.058), 3.2% at 18 months (P < 0.01), and 3.5% at 24 months (P <
      0.002). Differences of lesser statistical magnitude were seen at the femoral neck
      (between group differences at 2 yr: 2.7%, P = 0.24), Ward's triangle (5.0%, P =
      0.055), greater trochanter (3.6%, P = 0.056), total body (1.3%, P = 0.046), legs
      (1.3%, P = 0.065), and trunk (2.0%, P = 0.029). There were no major adverse
      events. These data support the view that the likely cause of DMPA-associated bone
      loss is estrogen deficiency and demonstrate that it can be arrested by estrogen
      replacement therapy.

PMID- 12519834
TI  - Insulin resistance in type 2 diabetes: association with truncal obesity, impaired
      fitness, and atypical malonyl coenzyme A regulation.
AB  - Abdominal obesity and physical inactivity are associated with insulin resistance
      in humans and contribute to the development of type 2 diabetes. Likewise,
      sustained increases in the concentration of malonyl coenzyme A (CoA), an
      inhibitor of fatty-acid oxidation, have been observed in muscle in association
      with insulin resistance and type 2 diabetes in various rodents. In the present
      study, we assessed whether these factors are present in a defined population of
      slightly overweight (body mass index, 26.2 kg/m2), insulin-resistant patients
      with type 2 diabetes. Thirteen type 2 diabetic men and 17 sex-, age-, and body
      mass index-matched control subjects were evaluated. Insulin sensitivity was
      assessed during a two-step euglycemic insulin clamp (infusion of 0.25 and 1.0
      mU/kg x min). The rates of glucose administered during the low-dose insulin clamp
      were 2.0 +/- 0.2 vs. 0.7 +/- 0.2 mg/kg body weight x min (P < 0.001) in the
      control and diabetic subjects, respectively; rates during the high-dose insulin
      clamp were 8.3 +/- 0.7 vs. 4.6 +/- 0.4 mg/kg body weight x min (P < 0.001) for
      controls and diabetic subjects. The diabetic patients had a significantly lower
      maximal oxygen uptake than control subjects (29.4 +/- 1.0 vs. 33.4 +/- 1.4 ml/kg
      x min; P = 0.03) and a greater total body fat mass (3.7 kg), mainly due to an
      increase in truncal fat (16.5 +/- 0.9 vs. 13.1 +/- 0.9 kg; P = 0.02). The plasma
      concentration of free fatty acid and the rate of fatty acid oxidation during the
      clamps were both higher in the diabetic subjects than the control subjects (P =
      0.002-0.007). In addition, during the high-dose insulin clamp, the increase in
      cytosolic citrate and malate in muscle, which parallels and regulates malonyl CoA
      levels, was significantly less in the diabetic patients (P < 0.05 vs. P < 0.001).
      Despite this, a similar increase in the concentration of malonyl CoA was observed
      in the two groups, suggesting an abnormality in malonyl CoA regulation in the
      diabetic subjects. In conclusion, the results confirm that insulin sensitivity is
      decreased in slightly overweight men with mild type 2 diabetes and that this
      correlates closely with an increase in truncal fat mass and a decrease in
      physical fitness. Whether the unexpectedly high levels of malonyl CoA in muscle,
      together with the diminished suppression of plasma free fatty acid, explains the
      insulin resistance of the diabetic patients during the clamp remains to be
      determined.

PMID- 12519835
TI  - Effect of growth hormone (GH) and/or testosterone replacement on the prostate in
      GH-deficient adult patients.
AB  - The prostate is a target organ of the GH and IGF-I axis because prostate
      hypertrophy is found in acromegaly, reduced prostate size is found in GH
      deficiency (GHD) patients, and additionally, IGF-I is reported to be a positive
      predictor factor of prostate cancer. To investigate whether GH replacement
      therapy in adult patients with GHD has adverse effects on the prostate, we
      studied the effect of 12-month GH or GH plus testosterone replacement on prostate
      pathophysiology in 24 adult patients with GHD (11 euandrogenemic and 13
      hypoandrogenemic), compared with 24 age-matched healthy controls. At study entry,
      GHD patients had lower prostate volume than controls (19.4 +/- 1.7 vs. 24.9 +/-
      1.7 ml; P = 0.03). After 12 months of treatment, all hypoandrogenemic patients
      achieved normal testosterone levels, and prostate volume increased in the
      patients to the same level as controls (25.0 +/- 1.9 ml). The percentage increase
      in prostate volume was greater in hypoandrogenemic patients receiving both GH and
      testosterone replacement (51 +/- 11%) than in those receiving GH replacement
      alone (15 +/- 3%; P < 0.0009). At baseline, prostate volume was similar in GHD
      patients below or above 60 yr of age (16.8 +/- 1.3 vs. 23 +/- 3.6 ml; P = 0.08),
      whereas after treatment it was higher in the latter patients (21.8 +/- 1.2 vs.
      29.5 +/- 3.9 ml; P = 0.04). Prostate-specific antigen (PSA) and free PSA did not
      change, whereas PSA density was significantly reduced after treatment in
      hypoandrogenemic patients; there was also no change in calcifications, cysts, or
      nodules. In conclusion, GH replacement restores prostate size to normal in both
      young and elderly patients, with no increase in prostate abnormalities. Because
      the simultaneous treatment with GH and testosterone induces an increase of
      prostate size by 50% of baseline on average, care is suggested in elderly
      patients with prostate hyperplasia to avoid any risk of prostate symptoms. In
      these cases, GH replacement might be performed sequentially to reduce the
      hypertrophic effect of combining GH and testosterone.

PMID- 12519836
TI  - The usefulness of the combined growth hormone (GH)-releasing hormone and arginine
      stimulation test in the diagnosis of radiation-induced GH deficiency is dependent
      on the post-irradiation time interval.
AB  - The diagnostic usefulness of the insulin tolerance test (ITT) in patients with
      radiation-induced GH deficiency (GHD) is well established, whereas that of the
      combined GHRH plus arginine stimulation test (AST) is unproven. Both tests were
      undertaken in 49 adult survivors (aged 16-53.7 yr), who were previously
      irradiated for non-pituitary brain tumors or leukemia, and 33 age-, gender-, and
      BMI-matched controls. The aims of the study were to examine the impact of the
      time interval after irradiation on the pattern of GH responsiveness to the two
      provocative tests and to establish the role of the GHRH + AST in the diagnosis of
      radiation-induced GHD. The median (range) peak GH responses to either test were
      significantly lower (P < 0.0001) in the patients [GHRH + AST, 19.9 (range, 2.7
      103.5) microg/liter; ITT, 5 (0.2-34.8) microg/liter] than in normals [GHRH + AST,
      55 (5.7-173.5) microg/liter; ITT, 23.8 (4.2-80) microg/liter]. In patients and
      normal controls, the median peak GH response to the GHRH + AST was significantly
      greater (P < 0.0001) than the response to the ITT. However, the ratio of the peak
      GH response to the GHRH + AST over that achieved with the ITT (discordancy ratio)
      was significantly higher (P = 0.007) in the patients (median, 3.45; range, 0.8
      53.5) compared with normals (median, 2; range, 0.34-18.6), consistent with
      dominant hypothalamic damage and relatively preserved somatotroph responsiveness.
      The peak GH response to the ITT fell significantly within 5 yr of irradiation
      with little further change over the subsequent 10 yr. In contrast, the peak GH
      response to the GHRH + AST barely changed within 5 yr of irradiation but
      subsequently declined significantly over the next 10 yr. Thus, the evolution of
      change in GH responsiveness to the two different stimuli over time was markedly
      different, resulting in a significantly raised discordancy ratio of 6 within the
      first 5 postirradiation years, which then normalized over the next 10 yr. The
      peak GH responses to the GHRH + AST and the discordancy ratio were negatively
      correlated with the time interval after irradiation (r = -0.40, P = 0.0037; and r
      = -0.4, P = 0.0046, respectively). On a practical clinical level, the discordancy
      between the GH test results was important; 50% of those classified as severely
      GHD patients by the ITT were judged normal or only GH insufficient by the GHRH +
      AST. In conclusion, these findings suggest that hypothalamic dysfunction occurs
      early and somatotroph dysfunction occurs late, following radiation damage to the
      hypothalamic-pituitary axis. This time dependency of somatotroph dysfunction may
      reflect either secondary somatotroph atrophy due to hypothalamic GHRH deficiency
      or delayed direct radiation-induced damage to the pituitary gland. The high false
      negative diagnosis rate for severe GHD makes the GHRH + AST an unreliable test in
      clinical practice when GH status is explored in the early years after cranial
      irradiation with the intention to treat.

PMID- 12519837
TI  - Screening strategies for the identification of multiple antibody-positive
      relatives of individuals with type 1 diabetes.
AB  - The objective of this study was to determine the extent to which different
      screening strategies could identify a population of nondiabetic relatives of a
      proband with type 1 diabetes who had two or more immunologic markers from the
      group consisting of islet cell antibodies (ICA), micro insulin autoantibodies
      (MIAA), GAD65 autoantibodies (GAA), and ICA512 autoantibodies (ICA512AA).
      Relatives of subjects with type 1 diabetes were screened for ICA as part of the
      Diabetes Prevention Trial-Type 1. A total of 71,148 samples were also tested for
      GAA and ICA512AA. IAA results were available on 17,207 of these samples using a
      protein A/protein G MIAA assay as well. The study population was defined to be
      those in which all four antibodies were tested. There were 1010 (5.9%) relatives
      with a single autoantibody on initial screening and 394 (2.3%) with two or more
      autoantibodies. GAA was more sensitive than ICA [GAA, 91% (357 of 394); ICA, 82%
      (324 of 394)] in the detection of multiple antibody-positive individuals. The
      addition of ICA512AA to GAA as a screening test increased sensitivity to 97% (381
      of 394), whereas adding ICA512AA to ICA as a screening test increased sensitivity
      to 93% (367 of 394). GAA and ICA identified somewhat nonoverlapping subgroups of
      multiple antibody-positive subjects. Thus, the substitution of GAA or ICA for the
      other failed to detect 8-17% of multiple antibody subjects. Higher ICA titers
      were associated with increased percentages of multiple antibody-positive
      subjects; 86% of subjects having Juvenile Diabetes Foundation titers of at least
      160 were positive for two or more antibodies. A screening strategy combining GAA
      and ICA512AA resulted in a higher sensitivity than using any marker individually,
      although statistically it was not significantly higher than using GAA alone.
      Screening for any three antibodies guaranteed that all multiple antibody-positive
      subjects were detected. Screening for two antibodies at one time and testing for
      the remaining antibodies among those who are positive for one resulted in a
      sensitivity of 99% for GAA and ICA, 97% for GAA and MIAA or GAA and ICA512AA, 93%
      for ICA512AA and ICA, 92% for MIAA and ICA, and 73% for ICA512AA and MIAA. From a
      laboratory perspective, screenings for GAA, ICA512AA, and MIAA are semiautomated
      tests with high throughput that, if used as initial screen, would identify at
      first testing 67% of the 2.3% of multiple antibody-positive relatives (100% if
      antibody-positive subjects are subsequently tested for ICA) as well as 4.7% of
      relatives with a single biochemical autoantibody, some of whom may convert to
      multiple autoantibody positivity on follow-up. Testing for ICA among relatives
      with one biochemical antibody would identify the remaining 33% of multiple
      antibody-positive relatives. Further follow-up and analysis of actual progression
      to diabetes will be essential to define actual diabetes risk in this large
      cohort.

PMID- 12519838
TI  - Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and
      constitutionally thin women.
AB  - Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in
      rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition
      to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects
      in both rodents and humans. As the endogenous peptide appears directly related to
      feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients
      before and after renutrition and in constitutionally thin subjects with body mass
      indexes (BMIs) equivalent to those of AN women but with no abnormal feeding
      behavior. The relationships between plasma ghrelin levels and other
      neuroendocrine and nutritional parameters, such as GH, leptin, T3, and cortisol,
      were also investigated. In AN patients, morning fasting plasma ghrelin levels
      were doubled compared with levels in controls, constitutionally thin subjects,
      and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and
      cortisol levels determined every 4 h were significantly increased, whereas 24-h
      plasma leptin levels were decreased in AN patients compared with controls and
      constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to
      control values in AN patients after renutrition. Constitutionally thin subjects
      displayed intermediate 24-h plasma ghrelin and leptin levels, significantly
      different from controls and AN patients, whereas GH and cortisol were not
      modified. Ghrelin was negatively correlated with BMI, leptin, and T(3) in
      controls, constitutionally thin subjects, and AN patients, whereas no correlation
      was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI
      or T3 were still correlated after renutrition, suggesting that ghrelin is also a
      good nutritional indicator. Basal and GHRH-stimulated GH release were
      significantly increased in AN patients only. In conclusion, ghrelin is increased
      in AN and constitutionally thin subjects who display very low BMI but different
      eating behaviors, suggesting that not only is ghrelin dependent on body fat mass,
      but it is also influenced by nutritional status. Even though endogenous ghrelin
      is not strictly correlated with basal GH secretion, it may be involved in the
      magnitude of GHRH-induced GH release in AN patients.

PMID- 12519839
TI  - Epitope heterogeneity of thyroid-stimulating antibodies predicts long-term
      outcome in Graves' patients treated with antithyroid drugs.
AB  - Differences in the epitopes of thyroid-stimulating antibodies (TSAbs) from
      patients with untreated Graves' disease were compared with long-term response to
      antithyroid drugs. Epitopes were measured using Chinese hamster ovary cells
      transfected with wild-type human TSH receptor (TSHR) and two receptor chimeras,
      wherein TSHR residues 9-165 or 90-165 had been substituted with comparable
      residues of the LH/chorionic gonadotropin receptor. Of 159 patients studied, 52
      (32.7%) exhibited positive TSAb activity with one or both chimera lines
      (heterogeneous group), and 107 (67.3%) had no activity with either (homogeneous
      group). Independent of all other parameters, patients with heterogeneous epitopes
      responded more favorably to oral antithyroid drugs than patients with homogeneous
      epitopes (65.4% vs. 41.9%, P = 0.011: estimated odds ratio by logistic
      regression, 2.17). Although most clinical parameters were not different at
      presentation, significant differences in the size of goiters, total T(3)
      concentrations, and titers of TSH-binding inhibitory Igs were evident in the
      successfully treated group (n = 80) by comparison to the group of patients whose
      treatment failed (n = 79). Alone, these three parameters did not predict outcome;
      however, when either of these parameters were considered together with epitope
      heterogeneity, predictability of a positive therapeutic response was increased to
      nearly 80%. Thus, the presence of TSAbs with a heterogeneous epitope in a patient
      with Graves' disease is not only associated with a favorable response to
      antithyroid drug treatment, it may help predict the response to treatment when
      the patient is initially seen.

PMID- 12519840
TI  - Prediction of response to growth hormone treatment in short children born small
      for gestational age: analysis of data from KIGS (Pharmacia International Growth
      Database).
AB  - A model was developed that allows physicians to individualize GH treatment in
      children born short for gestational age (SGA) who fail to show spontaneous catch
      up growth. Data from children (n = 613) in a large pharmacoepidemiological
      survey, the KIGS (Pharmacia International Growth Database), or who had
      participated in clinical trials were used to develop the model. Another group of
      similar children (n = 68) from KIGS was used for validation. In the first year of
      GH treatment, the growth response correlated positively with GH dose, weight at
      the start of GH treatment, and midparental height SD score and negatively with
      age at treatment start. Using this model, 52% of the variability of the growth
      response could be explained, with a mean error SD of 1.3 cm. GH dose was the most
      important response predictor (35% of variability), followed by age at treatment
      start. The second year growth response was best predicted by a three-parameter
      model (height velocity in yr 1 of treatment, age at start of treatment, and GH
      dose), which accounted for 34% of the variability, with an error SD of 1.1 cm.
      The first year response to GH treatment was the most important predictor of the
      second year response, accounting for 29% of the variability. No statistically
      significant differences between the predicted and observed growth responses were
      found when the models were applied to the validation groups. In conclusion, using
      simple variables, we have developed a model that can be used in clinical practice
      to adjust the GH dose to achieve the desired growth response in patients born
      SGA. Furthermore, this model can be used to provide patients with a realistic
      expectation of treatment and may help to identify compliance problems or other
      underlying causes of treatment failure.

PMID- 12519841
TI  - Free and total insulin-like growth factor (IGF)-I, -II, and IGF binding protein
      1, -2, and -3 serum levels in patients with active thyroid eye disease.
AB  - To determine whether serum levels of total (T) and free (F) IGF-I and -II and IGF
      binding protein (IGFBP),-1, -2, and -3 are normal in euthyroid patients with
      Graves' disease and active thyroid ophthalmopathy, we investigated the above
      mentioned parameters in 21 patients (11 male, 10 female) aged 50.8 +/- 11.8 yr
      (range 35-70) and 19 healthy individuals matched for age, gender, and body mass
      index. All patients had active thyroid eye disease (TED) with clinical activity
      scores > or = 4 and positive orbital octreoscan in both eyes. Serum T and F IGF-I
      and IGF-II were determined using noncompetitive time-resolved monoclonal
      immunofluorometric assays, IGFBP-1 was determined by an in-house RIA, IGFBP-2 by
      a novel in-house time-resolved immunofluorometric assay, whereas IGFBP-3 by an
      immunoradiometric assay. All data are expressed as mean +/- SD. Our results show
      that T and F IGF-I, -II, and IGFBP-1, -2, and -3 levels in patients were similar
      to controls and did not show any significant difference. Specifically, mean T IGF
      I for patients group was 131 (61), F IGF-I was 0.47 (0.16), T IGF-II was 1056
      (300), F IGF-II was 1.45 (0.54), IGFBP-1 was 33 (14), IGFBP-2 was 848 (377), and
      finally IGFBP-3 was 3953 (1422). For controls, mean T IGF-I was 146 (51), F IGF-I
      was 0.85 (0.43), T IGF-II was 939 (197), F IGF-II was 1.53 (0.53), IGFBP-1 was 44
      (24), IGFBP-2 was 764 (316) and finally IGFBP-3 was 3721 (1017). Furthermore, no
      statistically differences emerged in the ratio between molar weights of T IGF
      I/IGFBP-3 and T IGF-II/IGFBP-3, as well as to the F/T IGF-I and F/T IGF-II.
      Finally, no relationship was found between the levels of the above-mentioned
      parameters and clinical activity scores, octreoscan scores, and thyroid hormones.
      Our data demonstrate for the first time that serum levels of IGFs (including free
      fractions) and IGFBPs are not increased in euthyroid Graves' patients with active
      TED. The increased IGF levels in retrobulbar tissues previously described, appear
      to be independent of serum IGFs concentration and probably represent autocrine
      and/or paracrine activity.

PMID- 12519842
TI  - A population-based study of thyroid function after radiotherapy and chemotherapy
      for a childhood brain tumor.
AB  - The effect of craniospinal irradiation (CSI) vs. cranial irradiation (CIR) only
      with or without chemotherapy (CT) on the hypothalamus/pituitary (HP) thyroid axis
      was assessed in a population-based study of patients treated for a childhood
      brain tumor not directly involving the HP axis. Thyroid function was evaluated
      and compared with that in healthy controls (n = 27), measuring TSH, free T4,
      total T4, total T3, and TRH. The biological effective dose (BED) of radiotherapy,
      determined for the HP region and spine and expressed in grays (Gy) as BED, gives
      a means of expressing the biological effects of different dosage schedules in a
      uniform way. Seventy-one children (45 males and 26 females), less than 15 yr of
      age when diagnosed between 1970-1997 in the eastern part of Denmark, were
      included. Twenty-nine had received CSI, and 42 had received CIR only. The median
      age at time of radiotherapy was 8.4 yr (range, 0.8-14.9). The median length of
      follow-up was 12.0 yr (range, 2.0-28.0). There was no significant difference
      between CSI and the CIR only patients with respect to median BED to the HP
      region. Primary hypothyroidism was found in 24%, of whom 71% had been treated
      with CSI and 29% with CIR only; 73% had compensated hypothyroidism, and 27% had
      overt primary hypothyroidism. Central hypothyroidism was found in 6%. Free T4 and
      total T3 were significantly lower in the CSI and CIR only groups compared with
      controls. As the CIR only group had significantly higher median basal TSH levels
      compared with controls and as the CSI compared with the CIR only group and
      controls had significantly higher median basal TSH levels, we speculate that this
      was probably due to scattered irradiation from both cranial and spinal fields to
      the thyroid gland. There was a significant relation between basal TSH and time of
      follow-up (r(s) = -0.39; P = 0.001). Stepwise backward multiple linear regression
      analysis showed that the best-fit model to predict basal TSH was free T4 (P <
      0.0001), the length of follow-up (P = 0.02), and total T3 (P = 0.06). In
      contrast, age at radiotherapy, BED to the HP region and spine, and whether the
      patient had been treated with CT were not included in the model. The TRH test
      showed significantly exaggerated and prolonged TSH responses for the CSI and CIR
      only groups compared with controls, indicating HP dysfunction. In conclusion,
      these data suggest that both CSI and CIR for childhood brain tumor may affect the
      HP-thyroid axis, resulting in hypothyroidism. CT had no significant influence on
      HP-thyroid function. We recommend prolonged surveillance of pituitary-thyroid
      function in long-term survivors of childhood brain tumor and institution of
      thyroid hormone replacement if the levels of TSH and free T4 are above and below
      the normal range, respectively, to ensure normal growth and metabolism.

PMID- 12519843
TI  - Hormonal profile of women with self-reported symptoms of oligomenorrhea and/or
      hirsutism: Northern Finland birth cohort 1966 study.
AB  - The hormonal profiles of nested female patients (n = 500) with self-reported
      symptoms typical of polycystic ovary syndrome (PCOS), oligomenorrhea, and/or
      hirsutism and their randomly selected controls (n = 1026) at the age of 31 yr
      were analyzed in a general population-based Northern Finland birth cohort 1966 to
      find out whether the symptomatic women also have the endocrine characteristics of
      PCOS and could be detected in a general population using simple questions. Higher
      medians of serum testosterone (T) (2.10 vs. 1.90 nmol/liter, P < 0.001), LH (5.40
      vs. 4.85 U/liter, P = 0.005), insulin (53.8 vs. 51.66 pmol/liter, P = 0.040), and
      free androgen index (FAI) (4.01 vs. 3.03, P < 0.001) and lower glucose/insulin
      ratio (91.1 x 10(8) vs. 94.9 x 10(8), P = 0.048) and SHBG (52.4 vs. 60.7
      nmol/liter, P < 0.001) were observed among the cases, but no difference was
      observed in cortisol and glucose levels between the cases and controls. Of all
      the women in the cohort, 10.2% reported only oligomenorrhea and had biochemical
      findings similar to the whole case group. Those who reported only hirsutism
      (10.4%) were in between the case and control groups according to biochemical
      findings. The subjects who reported both oligomenorrhea and hirsutism (3.4%) had
      the highest T, LH, FAI, insulin, and glucose and the lowest SHBG and
      glucose/insulin ratio, compared with the case group and the groups with either
      symptom only indicating a dose-response manner in typical endocrine profile of
      PCOS by adding up symptoms. The levels of T and FAI were higher and SHBG lower in
      groups with overweight or obesity both at 14 and 31 yr, compared with groups with
      normal weight at 14 yr and overweight or obesity at 31 yr. In the group with
      normal weight at 14 and 31 yr and the group with overweight or obesity at 14 yr
      but normal weight at 31 yr, the levels of T and FAI were lowest and SHBG highest.
      T and FAI were higher and SHBG lower among the cases than the controls in groups
      stratified by weight development from adolescence to adulthood. In conclusion,
      this longitudinal study of a large, stable population indicates that women with
      self-reported symptoms of hirsutism and/or oligomenorrhea show endocrine
      characteristics of PCOS and can be detected in a general population using simple
      questions. These symptoms are markers of the underlying metabolic alterations
      possibly associated with increased health risks in later life.

PMID- 12519844
TI  - Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of
      nonobese women with polycystic ovary syndrome: a randomized study.
AB  - Metformin, an insulin-sensitizing drug, has been shown to improve ovarian
      function and glucose metabolism in obese women with polycystic ovary syndrome
      (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not
      well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS
      were randomized to receive either metformin (500 mg twice daily for 3 months,
      then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35
      microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9).
      Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin
      during a 75-g oral glucose tolerance test; early phase insulin and C-peptide
      secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were
      assessed at baseline and at 3 and 6 months of treatment. Metformin did not have
      any effect on glucose tolerance or insulin sensitivity, but fasting insulin
      concentrations decreased from 44.4 +/- 5.1 (SE) to 29.8 +/- 4.3 pmol/liter (P =
      0.03), the waist to hip ratio decreased from 0.78 +/- 0.01 to 0.75 +/- 0.01 (P =
      0.01), and hepatic insulin clearance increased during the treatment. Furthermore,
      metformin decreased serum testosterone levels from 2.7 +/- 0.3 to 2.0 +/- 0.2
      nmol/liter (P = 0.01) and improved menstrual cyclicity. EE-CA did not have any
      significant effect on glucose tolerance, serum insulin levels, or insulin
      sensitivity, but it increased slightly the body mass index (P = 0.09) and
      significantly serum leptin concentrations (P < 0.001) and decreased serum
      testosterone levels from 2.1 +/- 0.2 to 1.4 +/- 0.2 nmol/liter (P = 0.03). In
      conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic
      symptoms associated with PCOS, but its possible negative effects on insulin and
      glucose metabolism also have to be taken into consideration in nonobese subjects.
      Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity,
      most likely through its positive effect on insulin clearance and abdominal
      adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with
      anovulation may also benefit from metformin treatment.

PMID- 12519845
TI  - Body fat content and 25-hydroxyvitamin D levels in healthy women.
AB  - Obesity is associated with alterations in the vitamin D endocrine system. Lower
      levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be
      secondary to an alteration in tissue distribution resulting from an increase in
      adipose mass. Therefore, morbidly obese individuals are expected to need higher
      doses of vitamin D supplementation than the general population. However, it is
      still unknown whether adiposity (or percentage body fat) should be taken into
      consideration while assessing vitamin D requirements in the general population.
      To study the relationship between 25-OHD levels and percentage body fat content
      in healthy women, we studied 410 healthy women between 20 and 80 yr of age with
      body mass index ranging from 17 to 30 kg/m2. We analyzed the correlation between
      serum 25-OHD level and percentage body fat measured by dual energy x-ray
      absorptiometry. We also analyzed the influence of season, dietary vitamin D
      intake, age, and race on this relationship. The levels of serum 25-OHD inversely
      correlated with percentage body fat. The correlation was -0.13 (P = 0.013) after
      adjusting for race, age, season, and dietary vitamin D intake. In a multiple
      stepwise regression, race and season were found to have a major influence on
      serum 25-OHD (cumulative R2 = 0.34), and percentage body fat, although modest
      (additional R2 = 0.02), also had an independent statistically significant
      influence on serum 25-OHD levels. We conclude, percentage body fat content is
      inversely related to the serum 25-OHD levels in healthy women.

PMID- 12519846
TI  - Six months of gluten-free diet do not influence autoantibody titers, but improve
      insulin secretion in subjects at high risk for type 1 diabetes.
AB  - Removal of gluten from the diet can attenuate the intensity of autoimmunity and
      reduces the incidence of diabetes in the nonobese diabetic mouse. In this study,
      we tested whether a gluten-free diet could reduce autoimmunity in human
      preclinical type 1 diabetes. A trial consisting of 6 months of a gluten-free diet
      followed by another 6 months of normal gluten-containing diet was performed in 17
      first-degree relatives with at least 2 antibodies among islet cell antibodies,
      glutamic acid decarboxylase autoantibodies, protein tyrosine islet antigen-2
      autoantibodies, and insulin autoantibodies. Treatment effect was measured as
      autoantibody titers and acute insulin response to iv glucose tolerance test. Two
      subjects dropped out for lack of compliance to diet restrictions. Of the
      remaining 15 subjects, 3 developed diabetes. Autoantibody titers did not show
      significant changes after 6 months of gluten-free diet and again after return to
      normal diet. Acute insulin response to iv glucose tolerance test significantly
      increased in 12 of 14 subjects after the first 6 months of gluten deprivation (P
      = 0.04) and decreased in 10 of 13 subjects during the following 6-month period of
      normal diet (P = 0.07). Insulin sensitivity (homeostasis model assessment-insulin
      resistance) nonsignificantly improved after the gluten-free diet and subsequently
      decreased (P < 0.005) after 6 months of normal diet. These findings indicate that
      6 months of gluten deprivation do not influence humoral autoimmunity, but may
      have a beneficial effect on preservation of beta-cell function in subjects at
      risk for type 1 diabetes.

PMID- 12519847
TI  - A randomized comparison of two ovarian stimulation protocols with gonadotropin
      releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization
      commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the
      standard long GnRH agonist protocol.
AB  - Extending the FSH window for multifollicular development by administering FSH
      from the midfollicular phase onward constitutes a novel mild protocol for ovarian
      stimulation for in vitro fertilization (IVF) based on the physiology of single
      dominant follicle selection in normo-ovulatory women. We compared outcomes from
      this protocol with two other stimulation protocols. One hundred and forty-two
      normo-ovulatory patients with an indication for IVF (or IVF/ICSI) were randomized
      to a GnRH agonist long protocol (group A; n = 45) or one of two GnRH antagonist
      protocols commencing recombinant FSH on cycle d 2 (group B; n = 48) or cycle d 5
      (group C; n = 49). A fixed dose (150 IU/d) of rFSH was used for ovarian
      stimulation, and GnRH antagonist cotreatment was initiated on the day when the
      leading follicle reached 14 mm diameter. Group C showed a shorter duration of
      stimulation (median duration, 11, 9, and 8 d for groups A, B, and C,
      respectively; P < 0.001), reflected in a significantly lower total dose of rFSH
      used (median amount of rFSH, 1650, 1350, and 1200 IU for groups A, B, and C,
      respectively; P < 0.001). In group C more cycles were cancelled during the
      stimulation phase due to insufficient response, resulting in a lower percentage
      of oocyte retrievals (84%, 73%, and 63% for groups A, B, and C; P = 0.02).
      However, women in group C obtained better quality embryos (percentage of embryo
      score of 1 for best embryo, 29%, 37%, and 61% for groups A, B, and C,
      respectively; P = 0.008), resulting in more transfers per oocyte retrieval (68%,
      71%, and 90% for groups A, B, and C, respectively; P = 0.04). After profound
      ovarian stimulation (groups A and B) only 7% of the patients who retrieved four
      oocytes or less conceived, whereas after mild stimulation (group C) 67% of these
      patients conceived (P < 0.01). Overall, no differences were found among the three
      groups comparing pregnancy rate per started IVF cycle. In conclusion, application
      of the described mild ovarian stimulation protocol resulted in pregnancy rates
      per started IVF cycle similar to those observed after profound stimulation with
      GnRH agonist cotreatment despite shorter stimulation and a 27% reduction in
      exogenous FSH. A higher cancellation rate before oocyte retrieval was compensated
      by improved embryo quality concomitant with a higher chance of undergoing embryo
      transfer. A relatively low number of oocytes retrieved after mild ovarian
      stimulation distinctly differs from the pathological reduction in the number of
      oocytes retrieved after profound ovarian stimulation (poor response) associated
      with poor IVF outcome. The relatively small number of oocytes obtained after mild
      ovarian stimulation may represent the best of the cohort in a given cycle.

PMID- 12519848
TI  - Serum ghrelin levels are inversely correlated with body mass index, age, and
      insulin concentrations in normal children and are markedly increased in Prader
      Willi syndrome.
AB  - Ghrelin, an endogenous ligand of the GH secretagogue receptor, stimulates
      appetite and causes obesity in animal models and in humans when given in
      pharmacologic doses. Prader-Willi Syndrome (PWS) is a genetic obesity syndrome
      characterized by GH deficiency and the onset of a voracious appetite and obesity
      in childhood. We, therefore, hypothesized that ghrelin levels may play a role in
      the expression of obesity in this syndrome. We measured fasting serum ghrelin
      levels in 13 PWS children with an average age of 9.5 yr (range, 5-15) and body
      mass index (BMI) of 31.3 kg/m2 (range, 22-46). The PWS group was compared with 4
      control groups: 20 normal weight controls matched for age and sex, 17 obese
      children (OC), and 14 children with melanocortin-4 receptor mutations (MC4)
      matched for age, sex, and BMI, and a group of 3 children with leptin deficiency
      (OB). In non-PWS subjects, ghrelin levels were inversely correlated with age (r =
      0.36, P = 0.007), insulin (r = 0.55, P < 0.001), and BMI (r = 0.62, P < 0.001),
      but not leptin. In children with PWS, fasting ghrelin concentrations were not
      significantly different compared with normal weight controls (mean +/- SD; 429 +/
      374 vs. 270 +/- 102 pmol/liter; P = 0.14). However, children with PWS did
      demonstrate higher fasting ghrelin concentrations (3- to 4-fold elevation)
      compared with all obese groups (OC, MC4, OB) (mean +/- SD; 429 +/- 374 vs. 139 +/
      70 pmol/liter; P < 0.001). In conclusion, ghrelin levels in children with PWS
      are significantly elevated (3- to 4-fold) compared with BMI-matched obese
      controls (OC, MC4, OB). Elevation of serum ghrelin levels to the degree
      documented in this study may play a role as an orexigenic factor driving the
      insatiable appetite and obesity found in PWS.

PMID- 12519849
TI  - Testicular volume in relation to hormonal indices of gonadal function in
      community-dwelling elderly men.
AB  - Aging is accompanied by involutional changes in testicular function; limited data
      suggest a decrease in bilateral testicular volume (BTV). We studied BTV by
      ultrasonography in relation to serum gonadal hormones in 115 healthy elderly men
      (median age, 78 yr) and 42 young men (median age, 26.5 yr). Elderly men had a
      clearly smaller BTV (mean, 20.6 vs. 29.7 ml; P < 0.001), whereas serum inhibin B
      was slightly but significantly decreased (mean, 176.8 vs. 212.8 ng/liter; P =
      0.04); lower values in the elderly were observed for bioavailable (Bio)
      testosterone (T), Bio 17 beta-estradiol, inhibin B/FSH (mean, 18 vs. 58 ng/mU; P
      < 0.001), and T/LH ratios. In the elderly and the young, respectively, BTV was
      associated with inhibin B (r = 0.53, P < 0.001; r = 0.41, P < 0.01), FSH (r = 
      0.53, P < 0.001; r = -0.48, P < 0.01), and inhibin B/FSH ratio. Only in the old
      men was BTV significantly associated with LH (r = -0.32; P < 0.001), Bio T (r =
      0.26; P < 0.01), and T/LH (r = 0.48; P < 0.001). In a multivariate analysis, FSH,
      inhibin B, and Bio T were independently associated with BTV in the elderly (R(2)
      = 0.34). Receiver operating characteristics curve analysis indicated that BTV at
      a criterion value of 14.3 ml had a sensitivity of 46% and a specificity of 79% to
      predict low serum Bio T levels in the elderly. In conclusion, the moderately
      decreased BTV observed in elderly men, strongly associated with a decrease of the
      inhibin B/FSH ratio, is consistent with a reduced Sertoli cell mass, compensated
      by increased FSH stimulation resulting in only limited decrease of Sertoli cell
      function. Finding of a low testicular volume in elderly men can contribute to the
      diagnosis of hypogonadism, but this criterion has low sensitivity to detect
      decreased T production.

PMID- 12519850
TI  - Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone
      relationship suggest a different reason why older adults require more vitamin D.
AB  - Vitamin D requirements are thought to vary with age, but there is little
      comparative evidence for this. One goal in establishing a vitamin D requirement
      is to avoid secondary hyperparathyroidism. We studied 1741 euthyroid, thyroid
      clinic outpatients without evidence of calcium abnormalities, ranging in age from
      19 to 97 yr, whose serum and urine had been analyzed for calcium, vitamin D, and
      parathyroid status. We found no effect of age on the 25-hydroxyvitamin D
      [25(OH)D] concentration associated with specific vitamin D intakes, and there was
      no relationship between 25(OH)D and 1,25hydroxyvitamin D [1,25(OH)2D]. In every
      age group, serum 1,25(OH)2D declined with increasing creatinine (P < 0.001). What
      changed with age included creatinine, which correlated with 25(OH)D (r = 0.146, P
      < 0.001) only in the youngest age group (19-50 yr) but not in the older age
      groups (P > 0.1). Creatinine did not correlate with PTH in the youngest age
      group, but the relationship became significant as age increased (e.g. for the
      elderly, r = 0.365, P < 0.001). Linear regression of log PTH vs. log 25(OH)D
      agreed with the natural shape of the relationship observed with scatterplot
      smoothing, and this showed no plateau in PTH as 25(OH)D increased. We compared
      PTH concentrations among age groups, based on 20 nmol/liter increments in
      25(OH)D. Mean PTH in adults older than 70 yr was consistently higher than in
      adults younger than 50 yr (P < 0.05 by ANOVA and Dunnett's t test). PTH levels of
      the elderly who had 25(OH)D concentrations greater than 100 nmol/liter matched
      PTH of younger adults having 25(OH)D concentrations near 70 nmol/liter. This
      study shows that all age groups exhibit a high prevalence of 25(OH)D
      insufficiency and secondary hyperparathyroidism. Older adults are just as
      efficient in maintaining 25(OH)D, but they need more vitamin D to produce the
      higher 25(OH)D concentrations required to overcome the hyperparathyroidism
      associated with their diminishing renal function.

PMID- 12519851
TI  - Influence of family history of type 2 diabetes on insulin sensitivity in
      prepubertal children.
AB  - The objective of this study was to examine the influence of positive family
      history (FH) of type 2 diabetes (T2D) on aspects of insulin resistance in
      prepubertal children. Twenty-one children (Tanner stage I or II) with a positive
      FH were compared with children with no FH. FH was defined by presence of T2D in a
      parent or grandparent as assessed by interview. The two groups of children were
      matched for age, gender, Tanner stage, ethnicity, geographical location, and body
      fat mass using a pair-matched design. These 21 pairs of children included
      Caucasian, African American, and Hispanic children who were studied either in
      Birmingham, Alabama, or Los Angeles, California, using similar techniques.
      Insulin sensitivity (S(I)) and the acute insulin response to glucose (AIR) were
      determined by an iv glucose tolerance test and minimal modeling, and body
      composition was determined by dual-energy x-ray absorptiometry. There were no
      significant differences in fasting glucose or insulin, S(I), AIR, the disposition
      index (product of S(I) and AIR), or body composition between children with a FH
      vs. those without a FH of T2D, and there were no significant differences in these
      parameters when the data were analyzed separately in each ethnic group. In
      conclusion, a positive FH for T2D does not seem to have any significant effect on
      insulin sensitivity, as assessed by the minimal model and associated risk factors
      for T2D in young children.

PMID- 12519852
TI  - Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in
      predicting the lateralization of Cushing's disease pituitary microadenoma:
      influence of catheter position and anatomy of venous drainage.
AB  - Bilateral inferior petrosal sinus sampling (BIPSS) is the most reliable procedure
      for distinguishing Cushing's disease from ectopic ACTH secretion. However, it is
      less reliable at predicting the lateralization of the pituitary corticotroph
      microadenoma. We sought to determine whether this could be improved by taking
      into account the pattern of venous drainage and the precise location of the
      catheters. We retrospectively studied data from 86 patients who underwent BIPSS.
      Cushing's disease was predicted in 74 patients, of whom 69 underwent
      transsphenoidal surgery. Surgical cure was obtained in 65 patients, with
      identification of a corticotroph microadenoma in 58 cases. In 49 patients the
      location of the microadenoma predicted by the intersinus ACTH gradient could be
      compared with the pathologist's data. BIPSS accurately predicted the
      lateralization of the microadenoma in only 57% of these patients. Prediction was
      improved to 71% when both venograms and catheters were symmetric (35 patients).
      In this subgroup accuracy was 86% in patients with both catheters in the inferior
      petrosal sinuses compared with 50% in patients with both catheters in the
      cavernous sinuses (CS). Two transient sixth nerve palsies occurred during CS
      catheterization. Our data suggest that BIPSS results are much improved when
      venous drainage is symmetric. Catheterization of CS did not improve the results
      and was less safe.

PMID- 12519853
TI  - Differential effects of androgens and estrogens on bone turnover in normal men.
AB  - The physiologic role of androgens and estrogens in the maintenance of normal bone
      turnover in men is a fundamental issue in bone biology. To address this question,
      we randomized 70 men between the ages of 20 and 44 yr to receive one of three
      treatment regimens. Group 1 (n = 25) received a GnRH analog (goserelin acetate
      3.6 mg by sc injection every 4 wk) alone for 12 wk to suppress endogenous gonadal
      steroids to prepubertal levels. Group 2 (n = 22) received goserelin plus
      transdermal testosterone (Androderm 5 mg topically daily) to normalize
      circulating testosterone and estradiol levels. Group 3 (n = 23) received
      goserelin plus testosterone plus an aromatase inhibitor (anastrozole 1 mg orally
      daily) to induce selective estrogen deficiency. The selective effects of
      androgens and estrogens on skeletal homeostasis were then assessed by measuring
      changes in biochemical markers of bone turnover and analyzing the between-group
      differences. Bone resorption markers increased in both the hypogonadal group
      (group 1) and in the group with selective estrogen deficiency (group 3). Urinary
      deoxypyridinoline excretion increased more in group 1 than in group 3 (P =
      0.023), suggesting a significant effect of androgens on bone resorption, whereas
      serum N-telopeptide levels increased more in group 3 than in group 2 (P = 0.037),
      suggesting a significant effect of estrogen on bone resorption. Bone formation
      markers initially declined in all groups and then increased in groups 1 and 3.
      The between-group comparisons were consistent for all formation markers. Bone
      formation markers increased more in group 1 than in group 2 (P = 0.001, 0.037,
      0.005 for osteocalcin, carboxy-terminal propeptide of type I procollagen, and
      amino-terminal propeptide of type I procollagen, respectively). Bone formation
      markers also increased more in group 1 than in group 3 but these differences were
      not statistically significant (P = 0.065 0.073, 0.099 for osteocalcin, carboxy
      terminal propeptide of type I procollagen, and amino-terminal propeptide of type
      I procollagen, respectively). Taken together, these data suggest that both
      androgens and estrogens play independent and fundamental roles in regulating bone
      resorption in men. These data also suggest that androgens may play an important
      role in the regulation of bone formation in men.

PMID- 12519854
TI  - Cardiovascular safety of acute recombinant human thyrotropin administration to
      patients monitored for differentiated thyroid cancer.
AB  - Eleven patients who had undergone total thyroidectomy for differentiated thyroid
      cancer and who were on chronic TSH-suppressive therapy with levothyroxine (L-T4),
      underwent 24-h Holter electrocardiogram and Doppler-echocardiography before and
      after acute recombinant human TSH (rhTSH) administration for disease staging. The
      treatment, which was generally well tolerated, did not affect circulating thyroid
      hormones levels, nor did it have measurable effects on heart rate, rhythm, left
      ventricular morphology, or systo-diastolic function. Notably, arterial blood
      pressure tended to be slightly reduced after rhTSH administration, although in no
      instance did the patients become frankly symptomatic. Our data demonstrate that
      rhTSH does not alter cardiovascular function acutely. Consequently, it can safely
      be used in the routine staging of patients affected by differentiated thyroid
      cancer.

PMID- 12519855
TI  - Urinary free cortisol increases in adolescent caucasian females during
      perimenarche.
AB  - Urinary free cortisol (UFC) excretion has been thought to be constant during
      female reproductive maturation when normalized for body surface area. We sought
      to determine whether there are longitudinal changes in urinary free cortisol
      excretion during perimenarche in adolescent females. We performed a longitudinal
      study of 24-h UFC excretion obtained at 6-month intervals over a 4-yr period in a
      cohort of 112 adolescent non-Hispanic white perimenarchal females from south
      central Pennsylvania. The overall mean values (mean +/- SD) for UFC/24 h for all
      measurements between ages 12 and 17 yr was 67.4 +/- 43.8 micro g/24 h (to convert
      to nanomoles per day, multiply by 2.759). In our model, we found a significant
      positive association between UFC excretion with both gynecological age (P =
      0.002) and chronological age (P = 0.0001). For every incremental increase in
      Tanner stage, the UFC/BSA increased by 3.0 microg/24 h per square meter.
      Correcting the UFC values by both creatinine and BSA creates a fairly constant
      number (6.3 +/- 3.1 microg/mg per square meter per 24 h) over the age range 12-17
      yr represented in this study. An increase in cortisol excretion may be part of
      normal reproductive maturation.

PMID- 12519856
TI  - Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic
      patients and healthy subjects.
AB  - We have previously shown that type 2 diabetic patients have decreased plasma
      concentrations of glucagon-like peptide 1 (GLP-1) compared with healthy subjects
      after ingestion of a standard mixed meal. This decrease could be caused by
      differences in the metabolism of GLP-1. The objective of this study was to
      examine the pharmacokinetics of GLP-1 in healthy subjects and type 2 diabetic
      patients after iv bolus doses ranging from 2.5-25 nmol/subject. Bolus injections
      iv of 2.5, 5, 15, and 25 nmol of GLP-1 and a meal test were performed in six type
      2 diabetic patients [age, mean (range): 56 (48-67) yr; body mass index: 31.2
      (27.0-37.7) kg/m(2); fasting plasma glucose: 11.9 (8.3-14.3) mmol/liter;
      hemoglobin A(1C): 9.6 (7.0-12.5)%]. For comparison, six matched healthy subjects
      were examined. Peak plasma GLP-1 concentrations increased linearly with
      increasing doses of GLP-1 and were similar for type 2 diabetic patients and
      healthy subjects. The peak concentrations of total GLP-1 (C-terminal) after 2.5,
      5, 15, and 25 nmol of GLP-1 were 357 +/- 56, 647 +/- 141, 1978 +/- 276, 3435 +/-
      331 pmol/liter in the type 2 diabetic patients and 315 +/- 37, 676 +/- 64, 1848
      +/- 146, 3168 +/- 358 pmol/liter, respectively, in the healthy subjects (not
      statistically significant). Peak concentrations of the intact GLP-1 peptide (N
      terminal) were: 69 +/- 17, 156 +/- 44, 703 +/- 77, and 1070 +/- 117 pmol/liter in
      the type 2 diabetic patients and 75 +/- 14, 160 +/- 40, 664 +/- 79, 974 +/- 87 in
      the healthy subjects (not statistically significant). GLP-1 was eliminated
      rapidly with clearances of intact GLP-1 after 2.5, 5, 15, and 25 nmol of GLP-1
      amounting to: 9.0 +/- 5.0, 8.1 +/- 6.0, 4.0 +/- 1.0, 4.0 +/- 1.0 liter/min in
      type 2 diabetic patients and 8.4 +/- 4.2, 7.6 +/- 4.5, 5.0 +/- 2.0, 5.0 +/- 1.0
      liter/min in healthy subjects. The volume of distribution ranged from 9-26 liters
      per subject. No significant differences were found between healthy subjects and
      type 2 diabetic subjects. We conclude that elimination of GLP-1 is the same in
      obese type 2 diabetic patients and matched healthy subjects. The impaired
      incretin response seen after ingestion of a standard breakfast meal must
      therefore be caused by a decreased secretion of GLP-1 in type 2 diabetic
      patients.

PMID- 12519857
TI  - Contribution of plasma galactose and glucose to milk lactose synthesis during
      galactose ingestion.
AB  - We have previously demonstrated that plasma glucose contributed 80% in the fed
      and 60% in the fasted state to lactose synthesis in humans, and de novo synthesis
      in the breast contributing to both the glucose and galactose moieties accounted
      for the remaining 20% and 40%, respectively, of lactose. The present study was
      conducted to determine, in lactating women, whether oral galactose is directly
      incorporated from plasma galactose into glucose and galactose in milk lactose or
      via conversion of galactose to glucose in the liver. Six healthy exclusively
      breast-feeding women (30 +/- 2 yr) (mean +/- SE) ingested galactose at 22
      micromol x kg-1 x min-1 for 9 h after an overnight fast during infusion of [6,6
      2H2]glucose and [1-13C]galactose. We observed that 69 +/- 6% of glucose and 54 +/
      4% of galactose in lactose were derived directly from plasma glucose, whereas 7
      +/- 2% and 12 +/- 2% of glucose and galactose in lactose, respectively, were
      derived directly from plasma galactose. De novo synthesis of glucose and
      galactose via hexoneogenesis accounted for 25 +/- 8% and 35 +/- 6%, respectively.
      We conclude that during ingestion of galactose the contribution from plasma
      glucose to glucose and galactose in lactose was similar to that of a short-term
      fasting, but part of the de novo synthesis of glucose and galactose in the breast
      was replaced by direct uptake of galactose.

PMID- 12519858
TI  - Luteinizing hormone (LH)-responsive Cushing's syndrome: the demonstration of LH
      receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond
      to chorionic gonadotropin and serotonin agonists in vitro.
AB  - In a substantial part of adrenal adenomas and hyperplasias from patients with
      Cushing's syndrome, cortisol production is controlled by the expression of
      aberrant hormone receptors on adrenocortical cells. We present in vivo and in
      vitro data of two patients with a LH-responsive Cushing's syndrome based on ACTH
      independent bilateral adrenal hyperplasia. Patients 1 and 2 are women who
      presented with Cushing's syndrome and bilateral adrenal hyperplasia. Endocrine
      testing demonstrated absence of cortisol diurnal rhythm, insufficient cortisol
      suppression after 1 mg dexamethasone orally, and undetectable ACTH levels in both
      patients. Both patients were treated by laparoscopic biadrenalectomy. In in vivo
      testing, in patients 1 and 2, a profound cortisol rise was found after
      administration of GnRH [change in cortisol (Delta F), 118 and 106%,
      respectively], human CG (Delta F, 133 and 44%), LH (Delta F, 73 and 43%), ACTH
      (Delta F, 89 and 181%), and the 5-hydroxy-tryptamine receptor type 4 (5-HT(4))
      agonists cisapride (Delta F, 141 and 148%) and metoclopramide (Delta F, 189 and
      95%). In in vitro testing, adrenal cells from patient 2 responded, in a dose
      dependent fashion, with cortisol production after exposure to human CG (Delta F,
      45%), cisapride (Delta F, 68%), and metoclopramide (Delta F, 81%). ACTH induced
      cortisol production by cells from both patients (Delta F, 135 and 159%). In
      receptor studies, LH receptor mRNA was demonstrated in adrenal tissue of both
      patients but also in control adrenal tissue of two patients with persisting
      pituitary-dependent Cushing's syndrome treated by biadrenalectomy. In neither
      patient were mutations found in the ACTH receptor gene. LH-responsive Cushing's
      syndrome associated with bilateral adrenal hyperplasia may result from aberrant
      (or possibly increased) adrenal LH receptor expression. This variant is further
      characterized by adrenal responsiveness to 5-HT4 receptor agonists, possibly
      pointing to an interaction between LH and serotonin in the regulation of cortisol
      secretion. Despite the regulatory potential of LH and 5-HT4 receptor agonists on
      cortisol production in our patients, their adrenals seemed to be still sensitive
      to ACTH, both in vivo and in vitro.

PMID- 12519859
TI  - Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium
      of patients with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) affects approximately 5% of reproductive-age
      women and is characterized by anovulation and increased androgen production.
      Despite the ability to correct ovulatory disorders, pregnancy rates remain
      paradoxically low, and spontaneous pregnancy loss rates are high. To determine
      whether uterine dysfunction contributed to the adverse reproductive outcomes in
      PCOS, we assessed the effect of the increased ovarian androgens on a well
      characterized gene essential to endometrial receptivity. Up-regulation of HOXA10
      in the endometrium is necessary for receptivity to embryo implantation. In vitro,
      HOXA10 expression was repressed by testosterone but not by
      dehydroepiandrosterone, dehydroepiandrosterone sulfate, or insulin. Testosterone
      also prevented the increased expression of HOXA10 previously reported with
      estradiol or progesterone. Dihydrotestosterone produced an effect similar to that
      of testosterone, whereas flutamide blocked the testosterone effect. Endometrial
      biopsies, obtained from women with PCOS, demonstrated decreased HOXA10 mRNA.
      Testosterone is a novel regulator of HOXA10. Diminished uterine HOXA10 expression
      may contribute to the diminished reproduction potential of women with PCOS.

PMID- 12519860
TI  - Genetic variations in calpain-10 gene are not a major factor in the occurrence of
      type 2 diabetes in Japanese.
AB  - The 112/121 haplotype combination defined by the UCSNP-43, -19, and -63 alleles
      in the calpain-10 gene is associated with type 2 diabetes in Mexican Americans.
      To determine whether this genetic variation constitutes risk of type 2 diabetes
      in Japanese, we investigated its frequency in 177 patients with type 2 diabetes
      and 172 controls. Though this variation occurs in Japanese more frequently than
      in Mexican Americans, there is no significant difference in frequency between
      diabetic (29.9%) and control (31.9%) subjects. We also screened all exons and the
      putative promoter of the calpain-10 gene for mutations in 96 of the genotyped
      patients, resulting in the identification of 7 coding variants, including 3
      missense mutations and 5 nucleotide alterations in the promoter. However, their
      frequencies all are similar in patients and controls, suggesting that these
      genetic variations are not a major factor in the occurrence of type 2 diabetes in
      Japanese, although they could yet be associated with various phenotypes of the
      disease.

PMID- 12519861
TI  - Overexpression of serotonin4 receptors in cisapride-responsive
      adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia
      causing Cushing's syndrome.
AB  - The serotonin4 (5-HT4) receptor agonists cisapride and/or metoclopramide have
      been shown to stimulate cortisol secretion in some patients with ACTH-independent
      bilateral macronodular adrenal hyperplasias (AIMAH) causing Cushing's syndrome.
      In the present study, we have investigated quantitatively and qualitatively the
      expression of the 5-HT4 receptor in both normal adrenal cortex and tissues
      removed from six patients (P1-P6) with cisapride-responsive AIMAH and Cushing's
      syndrome. Real-time quantitative PCR assay revealed that the 5-HT4 receptor was
      overexpressed in four of the six hyperplasias studied when compared with normal
      adrenal cortex. In these tissues, 5-HT4 receptor mRNA expression was 3 to 16
      times higher than in normal glands, likely explaining the abnormal in vivo
      cortisol response to cisapride. Characterization of 5-HT4 receptor splice
      variants by RT-PCR in both hyperplastic and normal adrenals showed that the
      variants present in the two hyperplasias that did not overexpress the 5-HT4
      receptor, i.e. P2 and P5, could also be detected in the normal adrenal tissue. In
      addition, sequencing of the full-length cDNAs encoding 5-HT4 receptors in
      hyperplasias P2 and P5 did not reveal any mutation. Taken together, our results
      show an overexpression of the 5-HT4 receptor in cisapride-responsive AIMAH.
      However, in two cases, the level of expression of the receptor in the
      hyperplastic adrenal cortex was similar to that of normal adrenal gland. The
      enhanced sensitivity of these two tissues to 5-HT4 receptor agonists was not due
      to ectopic expression of 5-HT4 receptor isoforms or to the occurrence of somatic
      gain-of-function mutation of the receptor.

PMID- 12519862
TI  - Two promoter polymorphisms regulating interleukin-6 gene expression are
      associated with circulating levels of C-reactive protein and markers of bone
      resorption in postmenopausal women.
AB  - IL-6 is a pleiotropic cytokine that plays a critical role in bone resorption. We
      describe two allelic variants in the IL-6 promoter, -572 and -174 G-->C, that
      alone and in combination influence IL-6 activity in vitro and in vivo. The
      association of IL-6 -572 genotypes and -572/-174 G-->C haplotypes with serum C
      reactive protein (CRP), serum and urinary C-terminal cross-linking of type I
      collagen (a marker of bone resorption), and osteocalcin (a marker of bone
      formation) was investigated in a cohort of healthy postmenopausal women (n = 495;
      mean age +/- SD, 72 +/- 5.7 yr). Among IL-6 -572 genotypes, CRP was 37% higher (P
      = 0.02) and urinary C-terminal cross-linking of type I collagen was 20% higher (P
      = 0.01) in the presence of the C allele, whereas serum osteocalcin was not
      different. IL-6 -572/-174 haplotypes (G/C, G/G, and C/G) were significantly
      associated with all biochemical markers, and additive effects of the two
      polymorphic loci were found. Thus, there was a significant increase in the level
      of CRP (up to +79%; P = 0.007) and bone resorption markers (up to +32%; P =
      0.017) with a decreasing number (from four to one) of IL-6 protective alleles 
      572G and -174C. In addition, there was a trend for lower age-adjusted bone
      mineral density at the lumbar spine in subjects with less IL-6 protective alleles
      (up to -9.6%; P = 0.037; P = 0.08 after further adjustment for weight). In
      conclusion, we describe two functional polymorphisms in the IL-6 gene regulatory
      region associated with IL-6 activity in postmenopausal women, both systemically
      (CRP) and locally in bone. As such, IL-6 polymorphisms are able to influence the
      risk of osteoporosis as well as other chronic disorders involving IL-6 activity.

PMID- 12519863
TI  - Integrin-dependent cell growth and survival are mediated by different signals in
      thyroid cells.
AB  - Cell adhesion to extracellular matrix regulates proliferation and survival of
      several cell types including epithelial thyroid cells. Activation of integrin
      receptors by binding to extracellular matrix generates a complex cell type
      dependent signaling. Adhesion to extracellular matrix induces proliferation and
      survival in primary cultures of thyroid cells and induces survival in
      immortalized human thyrocytes. In this study we demonstrate that in immortalized
      human thyrocyte cells, adhesion to immobilized fibronectin (FN) stimulates DNA
      synthesis and proliferation through the p21Ras/MAPK pathway, whereas cell
      survival is mediated by phosphatidylinositol 3-kinase (PI3K) signal pathway.
      Integrin activation by immobilized FN induced phosphorylation of pp125 focal
      adhesion kinase and paxillin and induced the formation of focal adhesion
      kinase/Grb-2/Sos complex. Western blot and in vitro kinase assay demonstrated the
      activation of Ras and the p44/p42 MAPK/ERK1/2. Inhibition of p21Ras activity and
      inhibition of MAPK enzymatic activity completely arrested cell growth but did not
      induce cell death. Integrin activation by cell adhesion to FN also induced
      activation of PI3K. Inhibition of PI3K enzymatic activity induced apoptosis
      demonstrated by annexin V-binding assay and loss of cellular DNA content. These
      results demonstrate that in thyroid cells adhesion to FN regulates proliferation
      through the p21Ras/MAPK signal pathway, whereas integrin-mediated cell survival
      is mediated by PI3K.

PMID- 12519865
TI  - Cortistatin rather than somatostatin as a potential endogenous ligand for
      somatostatin receptors in the human immune system.
AB  - Cells of the human immune system have been shown to express somatostatin
      receptors (sst). The expression of sst suggests a functional role of the peptide
      somatostatin (SS). However, SS expression has not been demonstrated yet in
      different human immune tissues. Therefore, we investigated by RT-PCR the
      expression of both SS and cortistatin (CST), a SS-like peptide, in various human
      lymphoid tissues and immune cells. We detected SS mRNA expression in the human
      thymus only, while not in thymocytes. CST mRNA was clearly expressed in the
      immune cells, lymphoid tissues, and bone marrow. Using quantitative RT-PCR,
      significant differences in expression levels between tissues were demonstrated.
      Expression of CST mRNA was up-regulated during differentiation of monocytes into
      macrophages and dendritic cells and could be up-regulated by lipopolysaccharide
      stimulation. Two differently sized cDNA fragments of CST were detected in the
      majority of cells and tissues. However, although both fragments were detected in
      nearly all T-cell lines (7 of 8), most of the B-cell lines expressed the short
      fragment only (8 of 10). Using autoradiography, we showed that CST displaced
      [125I-Tyr3]octreotide binding with relatively high affinity on human thymic
      tissue and sst2-expressing cells. This is the first extensive study demonstrating
      that human lymphoid tissues and immune cells express different levels of CST mRNA
      and that its expression can be regulated. On the basis of these observations, we
      hypothesize a role for CST as an endogenous ligand of at least the sst2 receptor
      in the human immune system, rather than SS itself.

PMID- 12519866
TI  - Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid
      expression: a potential marker for glucocorticoid sensitivity, potency, and
      bioavailability.
AB  - To reduce the side effects of corticosteroid treatment, the administered dose of
      glucocorticoids (GCs) should be kept to a minimum while preserving
      therapeutically needed intracellular levels. Currently available assays to
      determine individual sensitivity to GCs are either imprecise or based on
      inhibition by GCs of lymphocyte proliferation following stimulation with
      phytohemagglutinin or other mitogens, which may influence the GC signal
      transduction pathway. Using the human lymphoblastoid cell line IM-9 as a model
      system, we studied whether the GC-induced increase of the mRNA encoding the 51
      kDa FK506-binding protein (FKBP51) could be used for the development of a novel
      assay, ultimately to be used in native human peripheral blood mononuclear cells
      (PBMCs). GC addition to IM-9 cells resulted in a dose-dependent increase of
      FKBP51 mRNA levels within 2 h, followed by a further increase until 24 h.
      Northern blot analysis and real-time PCR yielded similar results. Coincubation of
      GCs with the GC receptor antagonist ORG 34116 or the protein synthesis inhibitor
      cycloheximide suggested a direct, GC receptor-mediated up-regulation of FKBP51
      gene transcription. Expected differences in potency among different GCs could be
      readily demonstrated in this system. Extending our observations in IM-9
      lymphoblasts to normal PBMCs, we found a dose-dependent increase of FKBP51 mRNA
      on ex vivo incubation of native human PBMCs with GCs, with a sensitivity of about
      10(-9) M for dexamethasone. Moreover, dexamethasone ingestion increased FKBP51
      mRNA in PBMCs in vivo, extending the use of this assay to the measurement of GC
      bioavailability. Finally, using this method we were able to demonstrate partial
      GC-insensitivity in a 6-month-old infant suffering from congenital adrenal
      hyperplasia caused by 21-hydroxylase deficiency. We conclude that the induction
      of FKBP51 mRNA by GCs may be a suitable marker to assess individual GC
      sensitivity, the in vitro measurement of GC potency, and the in vivo
      determination of GC bioavailability.

PMID- 12519867
TI  - Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on
      insulin sensitivity in men with type 2 diabetes.
AB  - 11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) regenerates cortisol
      from inactive cortisone in liver and adipose tissue. Inhibition of 11 beta-HSD1
      offers a novel potential therapy to lower intracellular cortisol concentrations
      and thereby enhance insulin sensitivity and hepatic lipid catabolism in type 2
      diabetes, obesity, and hyperlipidemia. We evaluated this approach using the
      nonselective 11 beta-HSD inhibitor, carbenoxolone, in healthy men and lean male
      patients with type 2 diabetes. Six diet-controlled nonobese diabetic patients
      with hemoglobin A(1c) less than 8%, and six matched controls participated in a
      double-blind, cross-over comparison of carbenoxolone (100 mg every 8 h, orally,
      for 7 d) and placebo. They were admitted overnight for infusions of insulin (as
      required to maintain arterialized plasma glucose of 5.0 mM) and [13C6]glucose.
      Glucose kinetics were measured in the fasted state from 0700-0730 h, during a 3-h
      euglycemic hyperinsulinemic clamp (including somatostatin infusion and
      replacement of physiological GH and glucagon levels), and during a 2-h euglycemic
      hyperinsulinemic clamp with a 4-fold increase in glucagon levels. Data are the
      mean +/- SEM. Carbenoxolone had the expected effects of raising blood pressure
      and lowering plasma potassium. Carbenoxolone reduced total cholesterol in healthy
      subjects (5.25 +/- 0.34 vs. 4.78 +/- 0.40 mM; P < 0.01), but had no effect on
      other serum lipids or on cholesterol in diabetic patients. Carbenoxolone did not
      affect the rate of glucose disposal or the suppression of free fatty acids during
      hyperinsulinemia. However, carbenoxolone reduced the glucose production rate
      during hyperglucagonemia in diabetic patients (1.90 +/- 0.2 vs. 1.53 +/- 0.3
      mg/kg x min; P < 0.05). This was attributable to reduced glycogenolysis (1.31 +/-
      0.2 vs. 1.01 +/- 0.2 mg/kg x min; P < 0.005) rather than altered gluconeogenesis.
      These observations reinforce the potential metabolic benefits of inhibiting 11
      beta-HSD1 in the liver of patients with type 2 diabetes. Further studies in
      obesity and hyperlipidemia are now warranted. However, clinically useful
      therapeutic effects will probably require selective 11 beta-HSD1 inhibitors that
      lower intraadipose cortisol levels and enhance peripheral glucose uptake.

PMID- 12519868
TI  - Androgen-responsive aspects of cognition in girls with Turner syndrome.
AB  - Turner syndrome (TS) represents a unique, sex hormone-deficient model in which to
      study the biological effects of androgen treatment (replacement) on cognition in
      females because TS girls have gonadal dysgenesis and absent ovarian androgen and
      estrogen production. We investigated the effects of androgen replacement therapy
      in TS girls, ages 10-14 yr, on cognitive function. A total of 64 TS girls were
      randomized to receive oxandrolone or placebo for 2 yr. They had a cognitive
      evaluation of four domains (verbal abilities, spatial cognition, executive
      function, and working memory) at baseline, 1, and 2 yr of the study. In addition,
      all subjects were examined for study safety every 6 months. Three of the four
      domains studied did not change significantly in response to oxandrolone treatment
      (verbal abilities, spatial cognition, and executive function). In contrast, the
      working memory summary score had a significant group by time interaction. The
      oxandrolone-treated group demonstrated improved performance after 2 yr, compared
      with the placebo group (P < 0.03). Minimal or no side effects were observed. In
      conclusion, oxandrolone treatment for 2 yr improves working memory in adolescent
      girls with TS. What this degree of improvement will mean in real life terms for
      TS girls remains to be determined.

PMID- 12519869
TI  - Luteinizing hormone pulsatility is disrupted at a threshold of energy
      availability in regularly menstruating women.
AB  - To investigate the dependence of LH pulsatility on energy availability (dietary
      energy intake minus exercise energy expenditure), we measured LH pulsatility
      after manipulating the energy availability of 29 regularly menstruating,
      habitually sedentary, young women of normal body composition for 5 d in the early
      follicular phase. Subjects expended 15 kcal/kg of lean body mass (LBM) per day in
      supervised exercise at 70% of aerobic capacity while consuming a clinical dietary
      product to set energy availability at 45 and either 10, 20, or 30 kcal/kg LBM.d
      in two randomized trials separated by at least 2 months. Blood was sampled daily
      during treatments and at 10-min intervals for the next 24 h. Samples were assayed
      for LH, FSH, estradiol (E2), glucose, beta-hydroxybutyrate, insulin, cortisol,
      GH, IGF-I, IGF-I binding protein (IGFBP)-1, IGFBP-3, leptin, and T3. LH
      pulsatility was unaffected by an energy availability of 30 kcal/kg LBM.d (P >
      0.3), but below this threshold LH pulse frequency decreased, whereas LH pulse
      amplitude increased (all P < 0.04). This disruption was more extreme in women
      with short luteal phases (P < 0.01). These incremental effects most closely
      resembled the effects of energy availability on plasma glucose, beta
      hydroxybutyrate, GH, and cortisol and contrasted with the dependencies displayed
      by the other metabolic hormones (simultaneously P < 0.05). These results
      demonstrate that LH pulsatility is disrupted only below a threshold of energy
      availability deep into negative energy balance and suggest priorities for future
      investigations into the mechanism that mediates the nonlinear dependence of LH
      pulsatility on energy availability.

PMID- 12519870
TI  - The inhibition of growth hormone secretion presented in obesity is not mediated
      by the high leptin levels: a study in human leptin deficiency patients.
AB  - GH secretion is regulated by hypothalamic and peripheral hormones under a very
      complex interplay. Superimposed on this regulation, signals of a metabolic nature
      connect GH secretion with the metabolic and energetic homeostasis of a given
      individual. GH secretion is enhanced in malnutrition and is severely impeded in
      obesity, but no information is available to explain why GH secretion is severely
      impeded or blocked in excess adiposity. Obesity is associated with high plasma
      levels of leptin, and leptin participates at the hypothalamic and pituitary
      levels in the regulation of GH secretion. Thus, it has been postulated that the
      inhibitory action of obesity on GH discharge may be mediated by excess leptin
      levels. The only situation in which obesity does not parallel leptin values is
      the rare case of morbid obesity due to leptin deficiency caused by missense
      mutation of the leptin gene. To understand the causes of GH blockade presented in
      obesity, patients with both homozygous and heterozygous mutations of the leptin
      gene and matched controls for both sex and body mass index (BMI) were studied.
      Three homozygous and 5 heterozygous patients with leptin gene mutations as well
      as 13 control subjects were studied. In all subjects basal levels of leptin and
      GH values stimulated by the combined administration of GHRH plus GH-releasing
      peptide-6 (GHRP-6) were analyzed. To analyze the effects of obesity and leptin
      levels, 5 groups were designed, all them matched by sex and adiposity. The number
      of subjects (n), leptin levels in micrograms per liter, and adiposity in BMI were
      as follows: nonobese subjects: n = 5, BMI = 22.1 +/- 0.9 kg/m2, leptin = 5.4 +/-
      0.9; heterozygous patients: n = 5, BMI = 27.0 +/- 1.0 kg/m2, leptin = 2.3 +/-
      0.1; controls for the heterozygous group: n = 5, BMI = 24.7 +/- 1.1 kg/m2, leptin
      = 5.7 +/- 1.2; homozygous patients: n = 3, BMI = 54.4 +/- 0.2 kg/m2, leptin = 1.0
      +/- 0.2; and controls for the homozygous group: n = 3, BMI = 50.3 +/- 2.0 kg/m2,
      leptin = 35.0 +/- 6.6. In these matched groups, the GHRH- and GHRP-6-stimulated
      GH secretion (mean peak +/- SE; micrograms per liter) was: nonobese, 86.8 +/- 8.9
      [significantly higher than heterozygous (28.6 +/- 4.9) and control for
      heterozygous (39.9 +/- 10.4)]; homozygous group, 9.4 +/- 3.0; control for
      homozygous, 9.3 +/- 1.0 (significantly lower than the heterozygous, control for
      heterozygous, and nonobese groups). Hence, it appeared that GH discharge was
      negatively conditioned by adiposity and was not influenced by leptin levels. To
      further analyze this observation, a correlation analysis showed that GH peaks
      were negatively correlated with BMI in the 13 control subjects as well as in the
      8 leptin-deficient patients. On the contrary, the GH peaks were negatively
      correlated with leptin levels in controls, but showed the opposite pattern in
      homo- and heterozygous patients. In conclusion, the GH secretion blockade, which
      is characteristic of obese states, is due to adiposity or some factor linked to
      adiposity, but not to elevated plasma leptin levels.

PMID- 12519871
TI  - Polymorphisms of the insulin receptor substrate-2 in patients with type 2
      diabetes.
AB  - We investigated the significance of Gly1057Asp and Leu647Val insulin receptor
      substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose
      tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region
      (i.e. representative of central Italy), and 123 glucose-tolerant subjects from
      the Sicily region (i.e. representative of south Italy). The allelic frequency of
      Gly1057Asp variant did not differ between diabetics (32.9%) and nondiabetic
      subjects, whatever their ethnicity was (35.8% and 33.7% from Lazio and Sicily,
      respectively). As compared with Gly/Gly subjects within each group, Asp/Asp
      individuals showed no differences in quantitative traits, including fasting
      insulin and C-peptide, and several indices of insulin sensitivity and secretion.
      Only one of the diabetic patients was heterozygous for the Leu647Val variant, and
      none of the control subjects carried this variant. This patient had three
      children who were also heterozygous for this variant. They were glucose tolerant,
      and their insulin sensitivity and insulin secretion indices were within the range
      of age-matched controls. We also analyzed IRS-2 function in fibroblasts from
      carriers of Gly1057Asp or Leu647Val variant. No defects in IRS-2 expression,
      insulin-stimulated phosphorylation, or binding to the p85 subunit of
      phosphatidylinositol 3-kinase were observed. These results strongly argue against
      a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes.

PMID- 12519872
TI  - Termination of pregnancy with mifepristone and prostaglandin suppresses
      transiently circulating glucocorticoid bioactivity.
AB  - Mifepristone is a potent antiglucocorticoid, the administration of which results
      in a dose-dependent activation of the hypothalamic-pituitary-adrenal axis.
      However, the net effect of this compound on circulating glucocorticoid activity
      is not known. We have used a recombinant cell bioassay to study glucocorticoid
      bioactivity (GBA), measured directly from serum, in 18 women undergoing medical
      termination of an early pregnancy with 200 mg mifepristone, followed by 0.8 mg
      misoprostol, a prostaglandin. Increased serum mifepristone was accompanied by an
      increase in serum cortisol that was insufficient to maintain circulating GBA
      within the normal (pre-mifepristone) range (34.7-93.8 nM cortisol equivalents);
      after approximately 43, 46, and 68 h of mifepristone ingestion, the mean serum
      GBA levels were much lower than the mean pre-mifepristone level (P < 0.0001). At
      the corresponding times, 16, 13, and 12 women displayed subnormal serum GBA
      levels (ranges, <15.6-23, <15.6-25.6, and <15.6-32.5 nM cortisol equivalents,
      respectively). Altogether 11 subjects displayed subnormal serum GBA (range, <15.6
      32.5 nM cortisol equivalents) continuously in the presence of high concentrations
      of mifepristone. Two weeks after mifepristone administration, circulating GBA had
      returned to normal levels in all subjects. We conclude that 200 mg mifepristone
      elicits a significant suppression of serum GBA, to one third of the pretreatment
      value, despite the compensatory increase in the serum cortisol concentration.

PMID- 12519873
TI  - Characterization of human NOV in biological fluids: an enzyme immunoassay for the
      quantification of human NOV in sera from patients with diseases of the adrenal
      gland and of the nervous system.
AB  - Immunochromatography has shown that human NOV (NOVH), a member of the CCN
      (CTGF/CYR61/NOV) family, forms a physiological complex with fibulin-1 in blood.
      We developed an enzyme immunoassay specific for NOVH and showed for the first
      time that the concentration of NOVH differs in each of these biological fluids.
      The normal concentration of NOVH circulating in the blood is 350-400 ng/ml, but
      this concentration varies with age. By using sera from patients with adrenal
      gland diseases we found that in vivo ACTH or glucocorticoids are not responsible
      for the high concentration of NOVH in this endocrine gland. However, the NOVH
      concentration was significantly modified in malignant adrenocortical tumors, but
      not in benign adrenocortical tumors. The concentration of NOVH was significantly
      decreased in patients suffering from astrocytomas or multiple sclerosis, two
      diseases of the nervous system. Thus, NOVH is a potentially useful marker for the
      diagnosis of these diseases.

PMID- 12519874
TI  - Luteal phase deficiency in recreational runners: evidence for a hypometabolic
      state.
AB  - Exercising women with amenorrhea exhibit a hypometabolic state. The purpose of
      this study was to evaluate the relationship of luteal phase deficient (LPD)
      menstrual cycles to metabolic hormones, including thyroid, insulin, human GH
      (hGH), leptin, and IGF-I and its binding protein levels in recreational runners.
      Menstrual cycle status was determined for three consecutive cycles in sedentary
      and moderately active women. Menstrual status was defined as ovulatory or LPD.
      Subjects were either sedentary (n = 10) or moderately active (n = 20) and were
      matched for age (27.7 +/- 1.2 yr), body mass (60.2 +/- 3.3 kg), menstrual cycle
      length (28.4 +/- 0.9 d), and reproductive age (14.4 +/- 1.2 yr). Daily urine
      samples for the determination of estrone conjugates, pregnanediol 3-glucuronide,
      and urinary levels of LH were collected. Blood was collected on a single day
      during the follicular phase (d 2-6) of each menstrual cycle for analysis of TSH,
      insulin, total T3, total T4, free T4, leptin, hGH, IGF-I, and IGF binding protein
      (IGFBP)-1 and IGFBP-3. Among the 10 sedentary subjects, 28 of 31 menstrual cycles
      were categorized as ovulatory (SedOvul). Among the 20 exercising subjects, 24
      menstrual cycles were included in the ovulatory category (ExOvul), and 21
      menstrual cycles were included in the LPD category (ExLPD). TSH, total T4, and
      free T4 levels were not significantly different among the three categories of
      cycles. Total T3 was suppressed (P = 0.035) in the ExLPD (1.63 +/- 0.07
      nmol/liter) and the ExOvul categories of cycles (1.75 +/- 0.8 nmol/liter)
      compared with the SedOvul category of cycles (2.15 +/- 0.1 nmol/liter). Leptin
      levels were lower (P < 0.001) in both the ExOvul (5.2 +/- 0.4 microg/liter) and
      the ExLPD categories of cycles (5.1 +/- 0.4 microg/liter) when compared with the
      SedOvul category of cycles (13.7 +/- 1.7 microg/liter). Insulin was lower (P =
      0.009) only in the ExLPD category of cycles (31.9 +/- 2.8 pmol/liter) compared
      with the SedOvul (60.4 +/- 8.3 pmol/liter) and ExOvul (61.8 +/- 10.4 pmol/liter)
      categories of cycles. IGF-I, IGFBP-1, IGFBP-3, IGF-I/IGFBP-1, IGF-I/IGFBP-3, and
      hGH were comparable among the different categories of cycles. These data suggest
      that exercising women with LPD menstrual cycles exhibit hormonal alterations
      consistent with a hypometabolic state that is similar to that observed in
      amenorrheic athletes and other energy-deprived states, although not as
      comprehensive. These alterations may represent a metabolic adaptation to an
      intermittent short-term negative energy balance.

PMID- 12519875
TI  - Effect of discontinuation of growth hormone treatment on risk factors for
      cardiovascular disease in adolescents born small for gestational age.
AB  - Hyperlipidemia, diabetes mellitus type 2, and coronary heart disease have been
      associated with being born small for gestational age (SGA). It has been reported
      that GH treatment induced higher insulin levels, which has led to concern
      regarding the long-term effect of GH treatment in predisposed individuals such as
      children born SGA. In this study, we assessed the effect of discontinuation of
      long-term GH treatment in 47 adolescents born SGA on oral glucose tolerance
      tests, blood pressure (BP), and serum lipid levels for two GH dosage groups (3
      vs. 6 IU/m2 x d). At 6 months after discontinuation of GH treatment mean (SD) age
      was 16.0 (2.1) yr. Mean duration of GH treatment had been 6.9 (1.5) yr. Fasting
      glucose levels and 120-min area under the curve for glucose 6 months after
      discontinuation of GH treatment showed no difference from pretreatment levels for
      both GH dosage groups. After discontinuation of GH treatment, fasting insulin
      levels returned to pretreatment levels (8.4 mU/liter), whereas the 120-min area
      under the curve for insulin decreased, compared with 6-yr levels (P < 0.01),
      regardless of GH dosage group. No significant difference was found when levels
      were compared with a control group. In addition, for both GH dosage groups, no
      significant changes in systolic and diastolic BP SD score, total cholesterol, and
      atherogenic index (total cholesterol/high-density lipoprotein cholesterol) were
      seen from 6 yr of GH until 6 months after discontinuation of GH treatment. In
      conclusion, in children born SGA, the GH-induced insulin insensitivity
      disappeared after discontinuation of GH, even after long-term GH treatment.
      Furthermore, the beneficial effect of GH on BP was not changed after
      discontinuation of GH, and most children had normal lipid levels.

PMID- 12519876
TI  - Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid
      carcinomas and adenomas.
AB  - Chromosomal translocations encoding fusion oncoproteins are common in
      hematological malignancies, sarcomas, and papillary thyroid carcinomas. A recent
      study of follicular thyroid carcinomas reported a novel chromosomal
      translocation, t(2;3)(q13;p25), that fused the thyroid-specific transcription
      factor PAX8 with a nuclear receptor, peroxisome proliferator-activated receptor
      gamma (PPAR gamma). Herein we report the detection of this putative oncoprotein
      in 6 of 17 (35%) follicular thyroid carcinomas as well as in 6 of 11 (55%)
      follicular thyroid adenomas. Concordant expression of protein was found in 91% of
      those tumors in which PAX8-PPAR gamma mRNA was detected by RT-PCR, whereas a
      further 20% of follicular tumors were positive for PPAR gamma
      immunohistochemistry alone. Our findings suggest that the PAX8-PPAR gamma fusion
      protein promotes differentiated follicular thyroid neoplasia, although it is not
      sufficient per se for carcinogenesis.

PMID- 12519877
TI  - Differential anabolic effects of testosterone and amino acid feeding in older
      men.
AB  - The interaction between testosterone and exogenous amino acids was studied in
      older men before and after 6 months of testosterone administration. Twelve
      healthy older male subjects were randomly assigned in double-blind fashion to
      receive either testosterone enanthate [T; n = 7; 68 +/- 3 (+/-SE) yr] or placebo
      (n = 5; 67 +/- 3 yr) for 6 months. Muscle protein kinetics were determined using
      stable isotope methodology, arterial-venous difference across leg muscle, and
      muscle biopsies. In addition, ubiquitin-proteasome activity was measured in
      muscle biopsies as an indicator of muscle protein breakdown. T improved fasting
      net protein balance, although it remained significantly negative. The improvement
      in net balance was due to a decrease in muscle protein breakdown, as protein
      synthesis was unchanged. Ubiquitin-proteasome activity was also decreased with T.
      Exogenous amino acids increased protein synthesis in both placebo and T groups,
      but to a lesser degree after 6 months of T treatment. These results indicate that
      prolonged T administration increases net protein balance in the fasted state, but
      no additive effect is demonstrated when combined with amino acid feedings. Taken
      together, however, these diverse stimulatory effects can increase lean body mass
      and muscle strength over time.

PMID- 12519878
TI  - Reduced expression of corticotropin-releasing hormone receptor type-1 alpha in
      human preeclamptic and growth-restricted placentas.
AB  - Placentally derived CRH seems to play a major role in the mechanisms controlling
      human pregnancy and parturition, via activation of specific receptors widespread
      in reproductive tissues. In the human placenta, CRH seems to modulate
      vasodilation, prostaglandin production, and ACTH secretion. It has also been
      suggested that CRH might act as a placental clock, determining the length of
      gestation. In addition, maternal plasma CRH concentrations are further elevated
      in pregnancies associated with abnormal placental function, such as preeclampsia
      and intrauterine growth retardation (IUGR). In this study, we sought to
      investigate the expression of CRH-R1 alpha levels in placentas from women who
      have undergone normal deliveries (control group) and patients who have been
      diagnosed as having preeclampsia or IUGR. Results showed that placental CRH-R1
      alpha mRNA levels (as shown by quantitative RT-PCR) and protein levels (shown by
      Western blotting analysis) were significantly (P < 0.05) reduced in all of the
      complicated pregnancies. In contrast, levels of the angiotensin II receptor were
      elevated in preeclampsia and reduced in IUGR subjects, as shown by RT-PCR and
      Western blotting analysis. These findings might suggest that changes in receptor
      expression may contribute toward dysregulation of the dynamic balance controlling
      vascular resistance.

PMID- 12519879
TI  - Thyroglobulin-thyroperoxidase autoantibodies are polyreactive, not bispecific:
      analysis using human monoclonal autoantibodies.
AB  - Autoantibodies (Ab) to thyroglobulin (Tg) and to thyroid peroxidase (TPO) are
      reported to share common epitopes, and an assay for bispecific TgPOAb has been
      developed that may distinguish between different clinical presentations of
      thyroid autoimmunity. We sought to clone TgPOAb from an Ig gene combinatorial
      library constructed from B cells infiltrating the thyroid of a patient with
      TgPOAb. As described for isolating serum TgPOAb, we panned the phage display
      library by alternating from Tg- to TPO-coated ELISA wells. After panning, the
      library was enriched for TgPO-binding phage. Of 526 clones tested for expressed
      Ab, most were negative; 3 clones were specific for Tg, and 5 clones specifically
      recognized TPO. Antibody from a single clone, encoded by a non-Tg, non-TPO Ig
      heavy chain gene, bound both Tg and TPO (TgPO activity). However, this antibody
      also bound equally well to nonthyroid antigens. In conclusion, enrichment for Tg-
      and TPO-binding phage was largely attributable to phage specific for either Tg or
      TPO. This finding, albeit from a single patient, questions previous observations
      of serum TgPOAb prepared by affinity chromatography. Combined with the isolation
      of a polyreactive monoclonal antibody, our data provide powerful evidence against
      shared, cross-reactive epitopes on 2 major thyroid autoantigens.

PMID- 12519880
TI  - 11 beta-Hydroxysteroid dehydrogenase activity in hypothalamic obesity.
AB  - After extensive suprasellar operations for hypothalamic tumor removal, some
      patients develop Cushing-like morbid obesity while they receive replacement doses
      of glucocorticoids. In this study, we examined the hypothesis that target tissue
      conversion of inactive 11-ketosteroids to active 11 beta-OH glucocorticoids might
      explain the obesity of some patients with hypothalamic lesions. Toward this aim,
      we studied 10 patients with hypothalamic obesity and secondary adrenal
      insufficiency and 6 control Addisonian patients while they were on glucocorticoid
      replacement therapy. Pituitary hormone deficiencies were replaced when medically
      indicated. Twenty-four-hour urine was collected after a single oral dose of 12
      mg/m(2) hydrocortisone acetate. The ratios of free and conjugated cortisol (F) to
      cortisone (E) and their metabolites, [tetrahydrocortisol (THF)+5 alpha
      THF]/tetrahyrdocortisone (THE), dihydrocortisols/dihydrocortisones,
      cortols/cortolones, and (F+E)/(THF+THE+5 alpha THF), were considered to represent
      11 beta-hydroxysteroid dehydrogenase (HSD) activity. The 11-OH/11-oxo ratios were
      significantly higher in the urine of patients with hypothalamic obesity. The 11
      OH/11-oxo ratios, however, did not correlate with the degree of obesity, yet a
      significant correlation was found between conjugated F/E and the ratio of
      visceral fat to sc fat measured by computerized tomography at the umbilical
      level. The consequence of increased 11 beta-HSD1 activity and the shift of the
      interconversion toward cortisol may contribute to the effects of the latter in
      adipose tissue. We propose that deficiency of hypothalamic messengers after
      surgical injury induces a paracrine/autocrine effect of enhanced glucocorticoid
      activity due to up-regulated 11 beta-HSD1 activity.

PMID- 12519881
TI  - Modulation of 11 beta-hydroxysteroid dehydrogenase type 1 in mature human
      subcutaneous adipocytes by hypothalamic messengers.
AB  - Glucocorticoids are regulated at the prereceptor level by 11 beta-hydroxysteroid
      dehydrogenase (11 beta-HSD), which interconverts inactive cortisone and active
      cortisol. In a previous study, we noted that patients with hypothalamic obesity
      had an increased ratio of cortisol/cortisone metabolites, suggesting enhanced 11
      beta-HSD-1 activity. In this in vitro study, we tested the hypothesis that
      adipose 11 beta-HSD-1 is regulated by the hypothalamus via circulating hormones,
      sympathetic nervous system innervation, and/or cytokines. Preadipocytes were
      retrieved from sc fat from healthy nonobese individuals and differentiated in
      vitro to mature adipocytes. Cells were incubated with several potential
      effectors, and the activity of 11 beta-HSD-1 was assayed by measuring conversion
      of added 500 nM cortisone to cortisol. Expression of 11 beta-HSD-1 mRNA was
      determined by real-time PCR, whereas lipolytic effects were determined by
      measuring glycerol concentration in the culture medium. CRH down-regulated 11
      beta-HSD-1 activity with maximal effect at 10(-9)M (65 +/- 10% of control; P <
      0.001) and caused a reduction in lipolysis. Likewise, ACTH down-regulated 11 beta
      HSD-1 activity with maximal effect at 10(-9) M (65 +/- 20%; P < 0.05) and reduced
      medium glycerol. Neither CRH nor ACTH affected 11 beta-HSD-1 mRNA expression. TNF
      alpha up-regulated 11 beta-HSD-1 activity maximally at 0.6 x 10(-9) M (140 +/-
      20%; P < 0.001); the same cytokine increased 11 beta-HSD-1 mRNA levels to 3-fold
      of control (P < 0.05) and increased medium glycerol levels to 165 +/- 14% of
      control (P < 0.01). IL-1 beta also up-regulated 11 beta-HSD-1 activity maximally
      at 0.6 x 10(-9) M (160 +/- 33%; P < 0.001) and caused an increase in glycerol
      levels (159 +/- 11% of control; P < 0.001). Of the adrenergic agonists,
      salbutamol up-regulated 11 beta-HSD-1 activity maximally at 10(-7) M (162 +/-
      46%; P < 0.02), and clonidine down-regulated it at 10(-7) M (82 +/- 15%; P <
      0.005). We conclude that possible distinct hypothalamic mediators regulating
      adipose tissue 11 beta-HSD-1 might include down-regulation of 11 beta-HSD-1
      activity by CRH, ACTH, and alpha 2 sympathetic stimulation, and up-regulation of
      the enzyme by beta 2 sympathetic stimulation and by the cytokines TNFalpha and IL
      1 beta.

PMID- 12519882
TI  - The growth hormone/insulin-like growth factor-I axis hormones and bone markers in
      elite athletes in response to a maximum exercise test.
AB  - The aim of the GH-2000 project is to develop a method for detecting GH doping
      among athletes. Previous papers in the GH-2000 project have proposed that a
      forthcoming method to detect GH doping will need specific components from the
      GH/IGF-I axis and bone markers because these specific variables seem more
      sensitive to exogenous GH than to exercise. The present study examined the
      responses of the serum concentrations of these specific variables to a maximum
      exercise test in elite athletes from selected sports. A total of 117 elite
      athletes (84 males and 33 females; mean age, 25 yr; range, 18-53 yr) from
      Denmark, the United Kingdom, Italy, and Sweden participated in the study. The
      serum concentrations of total GH, GH22 kDa, IGF-I, IGF binding protein (IGFBP)-2,
      IGFBP-3, acid-labile subunit, procollagen type III (P-III-P), and the bone
      markers osteocalcin, carboxy-terminal cross-linked telopeptide of type I collagen
      (ICTP), and carboxy-terminal propeptide of type I procollagen were measured. The
      maximum exercise test showed, in both genders, a peak concentration of total GH
      (P < 0.001) and GH22 kDa (P < 0.001) by the time exercise ended compared with
      baseline, and a subsequent decrease to baseline levels within 30-60 min after
      exercise. The mean time to peak value for total GH and GH22 kDa was significantly
      shorter in males than females (P < 0.001). The components of the IGF-I axis
      showed a similar pattern, with a peak value after exercise compared with baseline
      for IGF-I (P < 0.001, males and females); IGFBP-3 (P < 0.001, males and females);
      acid-labile subunit [P < 0.001, males; not significant (NS), females], and IGFBP
      2 (P < 0.05, females; NS, males). The serum concentrations of the bone markers
      ICTP (P < 0.001, males; P < 0.05, females) and P-III-P (P < 0.001, males and
      females) increased in both genders, with a peak value in the direct post-exercise
      phase and a subsequent decrease to baseline levels or below within 120 min. The
      osteocalcin and propeptide of type I procollagen values did not change during the
      exercise test. Specific reference ranges for each variable in the GH/IGF-I axis
      and bone markers at specific time points are presented. Most of the variables
      correlated negatively with age. In summary, the maximum exercise test showed a
      rather uniform pattern, with peak concentrations of the GH/IGF-I axis hormones
      and the bone markers ICTP and P-III-P immediately after exercise, followed by a
      subsequent decrease to baseline levels. The time to peak value for total GH and
      GH22 kDa was significantly shorter for females compared with males. This paper
      presents reference ranges for each marker in each gender at specific time points
      in connection to a maximum exercise test to be used in the development of a test
      for detection of GH abuse in sports.

PMID- 12519883
TI  - Intact sympathetic nervous system is required for leptin effects on resting
      metabolic rate in people with spinal cord injury.
AB  - Compared with able-bodied (AB), people with spinal cord injury (SCI) have a 3- to
      5-fold higher risk of developing type 2 diabetes mellitus, which may be
      associated with increased fat mass. Evidence suggests that leptin regulates body
      adiposity through the sympathetic nervous system, which is impaired in people
      with high lesion SCI. The purpose of this study was to determine the relationship
      among leptin levels, body composition, and resting metabolic rate (RMR) in people
      with high lesion SCI and body mass index-, weight-, height-, and waist
      circumference-matched AB subjects. Fourteen subjects (seven SCI and seven AB)
      participated in the study. After an overnight fast, various hormones, glucose,
      and RMR were measured. There was no significant difference in plasma glucose,
      insulin, GH, cortisol, and glucagon levels between the two groups. The SCI group
      had 105% higher plasma leptin levels than the AB group (P < 0.05). Plasma leptin
      levels correlated with body mass index (SCI: r = 0.80; P = 0.028; AB: r = 0.79; P
      = 0.035) and fat mass (SCI: r = 0.95; P = 0.001; AB: r = 78; P = 0.038) in both
      groups. The plasma leptin level correlated with the absolute RMR (SCI: r = 0.15;
      P = 0.75; AB: r = 0.99; P < 0.006) and the RMR per unit fat-free mass (SCI: r = 
      0.70; P < 0.08; AB: r = 0.845; P < 0.017) in the AB group, but not in the SCI
      group. The absolute RMR was significantly reduced in the SCI group compared with
      the AB group, but there was no difference in the relative RMR between the groups.
      In conclusion, the SCI group has a significantly higher plasma leptin level than
      the AB group. The absolute and relative RMR correlated with leptin only in the AB
      group.

PMID- 12519884
TI  - CXC chemokine receptor 4 expression and function in human anaplastic thyroid
      cancer cells.
AB  - Anaplastic thyroid carcinomas (ATCs) are highly aggressive, extremely lethal
      human cancers with poor therapeutic response. Chemokines are a superfamily of
      small cytokine-like proteins that induce, through their interaction with G
      protein-coupled receptors, cytoskeletal rearrangement, firm adhesion to
      endothelial cells, and directional migration. In this study, we characterized the
      expression of CXC chemokine receptor 4 (CXCR4) and analyzed its functions in ARO
      cells, a human ATC cell. The normal primary cultured thyroid cells and ATC cell
      lines expressed CXCR4 and stromal cell-derived factor (SDF)-1 alpha transcripts,
      detected by RT-PCR. Fluorescence activated cell sorting analysis of CXCR4
      expression in normal and ATC cells showed that ARO cells expressed significant
      levels of CXCR4. FRO, NPA, and normal thyroid cells did not express membrane
      CXCR4, as determined by fluorescence activated cell sorting analysis. To identify
      the functional role of CXCR4 in ARO cells, we treated ARO cells with SDF-1 alpha
      and analyzed the signaling pathways, cellular migration, and proliferation. SDF
      1alpha enhanced the migration but did not affect the proliferation of ARO cells
      or activate the Janus kinase/signal transducer and activator of transcription
      signaling pathways. However, SDF-1 alpha/CXCR4 activation resulted in
      phosphorylation of the p70S6 kinase and its target protein, ribosomal S6 protein,
      and also activation of the ERK1/ERK2 signaling pathways. Furthermore, SDF-1
      alpha/CXCR4- mediated activation of the p70S6 kinase and phosphorylation of the
      S6 protein were inhibited by treatment with an mTOR/FRAP inhibitor. The
      specificity of the CXCR4-mediated migration of ARO cells was demonstrated by the
      dose-dependent inhibition of migration by neutralizing anti-CXCR4. The ATC cells,
      FRO and NPA, which do not express CXCR4, did not demonstrate significant SDF-1
      alpha-mediated migration in vitro. In addition, the CXCR4-mediated migration of
      ARO cells was inhibited by treatment with pertussis toxin (a Gi-protein
      inhibitor) and PD 98059 (a mitogen-activated ERK kinase inhibitor) but not by
      LY294002 and wortmanin, phosphatidylinositol 3-kinase inhibitors. These findings
      suggest that a subset of ATC cells expresses functional CXCR4, which may be
      important in tumor cell migration and local tumor invasion.

PMID- 12519885
TI  - An alternate translation initiation site circumvents an amino-terminal DAX1
      nonsense mutation leading to a mild form of X-linked adrenal hypoplasia
      congenita.
AB  - Mutations in DAX1 [dosage-sensitive sex reversal-adrenal hypoplasia congenita
      (AHC) critical region on the X chromosome gene 1; NR0B1] cause X-linked AHC, a
      disease characterized by primary adrenal failure in infancy or childhood and
      reproductive abnormalities later in life. Most of these patients have nonsense or
      frameshift mutations that cause premature truncation of the DAX1 protein, thereby
      eliminating its transcriptional silencing activity. We evaluated a patient with
      an unusual form of AHC manifest as late-onset adrenal insufficiency and gonadal
      failure. DNA sequence analysis revealed a novel amino-terminal DAX1 nonsense
      mutation (Q37X), predicted to cause a severe truncation of the protein. Using a
      combination of in vitro translation assays and studies of DAX1 expression and
      function in transfected cells, we demonstrate that, in contrast to more distal
      mutations leading to a nonfunctional protein, this mutation is associated with a
      milder phenotype due to the expression of a partially functional, amino-truncated
      DAX1 protein generated from an alternate in-frame translation start site
      (methionine, codon 83). The production of this amino-truncated isoform appears to
      rescue the classical AHC phenotype, thereby delaying the onset of clinically
      significant adrenal dysfunction until early adulthood. Thus, this case
      demonstrates a relatively rare phenomenon by which the clinical severity of an
      inherited human disease is reduced after alternate translation from a site
      downstream of a premature stop codon.

PMID- 12519886
TI  - Differential expression of two estrogen receptor beta isoforms in the human fetal
      testis during the second trimester of pregnancy.
AB  - Testicular cancer is more common in individuals with disorders of the male
      reproductive tract. It has been suggested that inappropriate exposure to
      estrogens during fetal life may have an impact on maturation of testicular germ
      cells that are the cells of origin of the majority of testis cancers. The aim of
      the present study was to establish whether human fetal germ cells (gonocytes) are
      a potential target of estrogen action. To address this issue, we used RT-PCR and
      immunohistochemistry to examine the pattern of expression of estrogen receptors
      (ER alpha, ER beta, and ER beta 2 variant) in human fetal testes at 12-19 wk
      gestation. ER alpha, mRNA, and protein were not detected in any of the fetal
      testes. In contrast, using an antibody directed against the hinge domain of ER
      beta expression was detected in multiple testicular nuclei. RT-PCR with primers
      specific for full-length wild-type ER beta (ER beta 1) or the ER beta 2 variant
      formed by splicing of an alternative eighth exon, was performed on whole-tissue
      extracts and materials recovered by laser capture and revealed that mRNAs for
      both isoforms were expressed. Immunohistochemistry with isotype-specific
      monoclonal antibodies showed that ER beta 1 was low/undetectable in gonocytes,
      whereas these cells expressed the highest levels of ER beta 2, compared with
      other testicular cell types. Both ER beta 1 and ER beta 2 were detected in some
      but not all Sertoli cells, peritubular cells, and other interstitial cells
      including those tentatively identified as Leydig cells. Our immunohistochemical
      results demonstrate that during the second trimester, some but not all somatic
      cells within the human fetal testis express wild-type ER beta (ER beta 1) protein
      and/or the variant isoform of ER beta (ER beta 2) that lacks amino acids
      essential for binding of estradiol. ER beta 2 protein was readily detectable in
      fetal gonocytes, whereas ER beta 1 was not. We did not detect expression of ER
      alpha. The expression of ER beta 2, a variant proposed act as a dominant negative
      receptor, might prevent estrogen action in gonocytes. We suggest that during this
      period of fetal life, estrogenic ligands are most likely to act on somatic cells
      that contain ER beta 1 protein.

PMID- 12519887
TI  - Expression and localization of prostaglandin E synthase isoforms in human fetal
      membranes in term and preterm labor.
AB  - Increased prostaglandin (PG) synthesis by fetal membranes occurs at parturition.
      PGE(2) synthesis from arachidonic acid involves multiple enzymes and two isoforms
      of the terminal enzyme of this biosynthetic pathway, PGE synthase (PGES), were
      recently identified. Cytosolic PGES (cPGES) is identical to the heat shock
      protein 90 chaperone, p23, and is reportedly functionally coupled to constitutive
      PG endoperoxide H synthase-1. Microsomal PGES (mPGES) is inducible by
      proinflammatory cytokines such as IL-1 beta. We have studied expression and
      localization of both enzyme isoforms in human fetal membranes either at term or
      preterm, with or without labor. The cPGES was immunolocalized in the amnion
      epithelium, and associated with fibroblasts and macrophages in the choriodecidual
      layer, whereas mPGES was localized in the amnion epithelium as well as the
      chorion trophoblast. Both enzymes were found to be associated with lipid
      particles present in the amnion epithelium, which are more prevalent in term
      tissues. Western blot analysis of the amnion and choriodecidua showed no
      differences in amounts of either cPGES or mPGES at term or preterm, with or
      without labor, in either tissue with advancing gestation. It does not appear that
      expression of PGES is the rate-limiting step in PGE2 synthesis in fetal membranes
      at labor.

PMID- 12519888
TI  - Steroid receptor expression in uterine natural killer cells.
AB  - The endometrium contains a unique subset of uterine-specific natural killer (uNK)
      cells, the proposed functions of which include a role in decidualization,
      menstruation, and implantation. These cells increase in number during the mid
      late secretory phase of the menstrual cycle and are also present in large numbers
      in early pregnancy. The cyclical nature of uNK cell appearance suggests hormonal
      regulation of these cells. To date, it has not been possible to localize either
      estrogen receptors (ERs) or progesterone receptors (PRs) to uNK cells. In the
      present study, we have investigated the steroid receptor expression of uNK cells,
      including not only ER alpha and PR but also wild-type ER beta 1, its variant form
      ER beta cx/beta 2, and glucocorticoid receptor (GR) using specific monoclonal
      antibodies and real-time quantitative RT-PCR. mRNA encoding ER alpha, PR, ER beta
      cx/beta 2, ER beta 1, and GR were identified in extracts of human endometrium
      across the menstrual cycle and in decidua. Quantitative real-time RT-PCR
      demonstrated an absence of ER alpha and PR mRNA in purified uNK cells. In
      contrast, mRNA for ER beta cx/beta 2, ER beta 1, and GR was present in uNK cells.
      ER alpha, PR, ER beta cx/beta 2, ER beta 1, and GR proteins were identified in
      endometrial and decidual biopsies. Colocalization using specific monoclonal
      antibodies confirmed that uNK cells were immunonegative for ER alpha and PR
      protein. These cells were also immunonegative for ER beta cx/beta 2 but did
      express ER beta 1 and GR proteins. These results raise the possibility that
      estrogens and glucocorticoids could be acting directly on uNK cells through ER
      beta and GR, respectively, to influence gene transcription in the endometrium and
      decidua.

PMID- 12519889
TI  - mt1 Melatonin receptor in the primate adrenal gland: inhibition of
      adrenocorticotropin-stimulated cortisol production by melatonin.
AB  - The pineal hormone melatonin participates in circadian, seasonal, and
      reproductive physiology. The presence of melatonin binding sites in human brain
      and peripheral tissues is well documented. However, in the mammalian adrenal
      gland, low-affinity melatonin binding sites have been detected only in the rat by
      some but not all authors. Conflicting evidence for a regulatory role of melatonin
      on adrenal cortisol production, prompted us to investigate this possibility in a
      New World primate, the capuchin monkey. Expression of melatonin receptors in the
      adrenal cortex was demonstrated through pharmacological characterization and
      autoradiographic localization of 2-[125I]iodomelatonin binding sites
      (dissociation constant = 96.9 +/- 15 pM; maximal binding capacity = 3.8 +/- 0.4
      fmol/mg protein). The mt1 identity of these receptors was established by cDNA
      sequencing. Melatonin treatment of dispersed cells and explants from adrenal
      gland did not affect basal cortisol production. However, cortisol production
      stimulated by 100 nM ACTH was significantly inhibited by low melatonin
      concentrations (0.1-100 nM); this inhibitory effect was reversed by the mt1/MT2
      melatonin antagonist luzindole. Melatonin also inhibited dibutyril-cAMP
      stimulated cortisol production, suggesting that melatonin acts through a cAMP
      independent signaling pathway. The present data demonstrate that the primate
      adrenal gland cortex expresses functional mt1 melatonin receptors and shows that
      melatonin inhibits ACTH-stimulated cortisol production.

PMID- 12519890
TI  - Amplification and overexpression of mutant RET in multiple endocrine neoplasia
      type 2-associated medullary thyroid carcinoma.
AB  - We have previously identified two second hit mechanisms involved in the
      development of multiple endocrine neoplasia type 2 (MEN 2)-associated tumors:
      trisomy 10 with duplication of the mutant RET allele and loss of the wild-type
      RET allele. However, some of the MEN 2-associated tumors investigated did not
      demonstrate either mechanism. Here, we studied the TT cell line derived from MEN
      2-associated medullary thyroid carcinoma with a RET germline mutation in codon
      634, for alternative mechanisms of tumorigenesis. Although we observed a 2:1
      ratio between mutant and wild-type RET at the genomic DNA level in this cell
      line, fluorescence in situ hybridization analysis revealed neither trisomy 10 nor
      loss of the normal chromosome 10. Instead, a tandem duplication event was
      responsible for amplification of mutant RET. In further studies we could for the
      first time demonstrate that the genomic chromosome 10 abnormalities in this cell
      line cause an increased production of mutant RET mRNA. These findings provide
      evidence for a third second hit mechanism resulting in overrepresentation and
      overexpression of mutant RET in MEN 2-associated tumors.

PMID- 12519891
TI  - Genetic mapping studies of familial juvenile hyperuricemic nephropathy on
      chromosome 16p11-p13.
AB  - Familial juvenile hyperuricemic nephropathy (FJHN), which is inherited as an
      autosomal dominant disorder, is characterized by hyperuricemia, a low fractional
      renal excretion of urate, and chronic renal failure that is associated with
      interstitial fibrosis. Studies in 4 families (3 European and 1 Japanese) have
      mapped the gene causing autosomal dominant FJHN to chromosome 16p11-p13. To
      refine this location we have pursued linkage studies in 7 European families with
      autosomal dominant FJHN and used 11 chromosome 16p11-p13 polymorphic loci whose
      order has been established as 16pter-D16S3069-D16S3060-D16S3041-D16S3036-D16S3046
      [D16S403,D16S417]-D16S420-D16S3113-D16S401-D16S3133-16cen. Cosegregation between
      these polymorphic loci and FJHN was observed in 5 of the families, and linkage
      was established between FJHN and 6 loci (peak LOD score, 5.32 with D16S417, at 0%
      recombination), with the most likely location of FJHN being within a 22
      centimorgan interval flanked centromerically by D16S401 and telomerically by
      D16S3069. Furthermore, FJHN in 2 families was found not to be linked to
      chromosome 16p11-p13, thereby demonstrating genetic heterogeneity. Thus, 5
      additional families with FJHN showing linkage to chromosome 16p11-p13 loci have
      been identified, and genetic heterogeneity has been demonstrated in more than 25%
      of FJHN families. These results will facilitate the characterization of this gene
      regulating urate metabolism.

PMID- 12519892
TI  - Fetal lung maturation in estrogen-deprived baboons.
AB  - We have previously shown that estrogen plays a central integrative role in
      regulating key aspects of fetal-placental development and that inhibition of
      estrogen production during the second half of baboon pregnancy suppressed fetal
      adrenal function. Because maturation of the fetal lung is dependent on cortisol
      of fetal adrenal origin, the current study determined whether lung development
      and expression of surfactant proteins (SPs) A and B were altered at term in
      estrogen-deprived baboons. Fetal lungs were obtained on d 100, 165, and 175 of
      gestation (term = d 184) from untreated baboons and on d 165 from animals treated
      daily during the second half of pregnancy either with the aromatase inhibitor CGS
      20267 alone or with CGS 20267 and estradiol benzoate. Umbilical venous estradiol
      levels were suppressed by more than 95% by CGS 20267 and elevated by CGS 20267
      and estrogen. Although umbilical serum cortisol levels were also suppressed by
      35% by CGS 20267, cortisol levels in the fetal lung of estrogen-suppressed
      baboons were similar to values in untreated animals. Immunocytochemistry
      demonstrated that CGS 20267 treatment did not alter fetal lung expression of the
      11 beta-hydroxysteroid dehydrogenase enzyme-1 enzyme catalyzing reduction of
      cortisone to cortisol. However, immunocytochemical expression of the 11 beta
      hydroxysteroid dehydrogenase enzyme-2 catalyzing oxidation of cortisol to
      cortisone appeared lower in lungs of estrogen-deprived fetuses and restored to
      normal by CGS 20267 and estrogen. SP-A levels in fetal lungs of untreated baboons
      were increased 16- to 20-fold between d 100 and d 165-175 of gestation in
      untreated baboons and baboons treated with CGS 20267 or CGS 20267 and estrogen.
      Similarly, SP-B levels in fetal lungs of untreated baboons were increased 10-fold
      between d 100 and d 165-175 of gestation in untreated baboons and baboons treated
      with CGS 20267 or CGS 20267 and estrogen. Moreover, in estrogen-suppressed
      baboons, as in untreated animals, the fetal lung continued to grow and exhibited
      normal alveolarization on histology. We conclude that development of the primate
      fetal lung can occur in utero in baboons in which fetal serum cortisol levels
      have been suppressed by the relative absence of estrogen perhaps because of the
      ability of the lung to coordinate local production of cortisol.

PMID- 12519893
TI  - Urocortin in human gastric mucosa: relationship to inflammatory activity.
AB  - The presence of CRH and urocortin (Ucn), members of the CRH family of
      neuropeptides, was examined in human gastric biopsies from normal controls and in
      patients with active gastritis from Helicobacter pylori (H. pylori) and after
      eradication treatment. RT-PCR analysis showed the presence of the Ucn transcript
      in biopsies (obtained by gastroscopy) from normal and inflamed gastric mucosa,
      whereas the CRH transcript was not detectable. Immunoreactive (ir-) Ucn was
      localized (by immunohistochemistry) in gastric epithelial cells and in
      inflammatory elements of the surrounding negative for Ucn gastric stroma. The
      level of ir-Ucn was higher in gastric biopsies from the group of patients with
      active H. pylori gastritis than in normal controls (10.4 +/- 1.8 vs. 2.0 +/- 1.3
      pg/ micro g total protein; P < 0.001). After the apparent eradication of H.
      pylori infection (by clinical and morphological criteria) ir-Ucn levels increased
      dramatically to 43.1 +/- 9.8 pg/ micro g total protein, (P < 0.001) compared with
      pretreatment values. Interestingly, nonresponders to the eradication treatment
      did not show any significant change in ir-Ucn levels (18.7 +/- 12.3 pg/ micro g
      total protein) compared with their pretreatment values. In conclusion, our data
      suggest that in human gastric epithelium Ucn is present and plays an important
      physiological role, whereas CRH is absent. In addition, and in contrast to what
      has been found for CRH in ulcerative colitis, a highly significant, but negative,
      correlation has been found between Ucn levels and gastric inflammation,
      suggesting that Ucn may exert an antiinflammatory effect in gastric mucosa.

PMID- 12519895
TI  - Placental 11 beta-hydroxysteroid dehydrogenase-2 and fetal cortisol/cortisone
      shuttle in small preterm infants.
AB  - Glucocorticoids rate among the most controversial topics in today's perinatology
      and neonatology. Many sick preterm infants exhibit signs of adrenal
      insufficiency, the etiology, diagnostic criteria, and optimal treatment of which
      are under debate. Moreover, most of these infants are exposed to pharmacological
      glucocorticoid doses both in utero and after birth. In face of this, surprisingly
      little is known about the physiological glucocorticoid exposure before early
      preterm birth. This exposure is highly variable and mainly regulated by the
      placental enzyme 11 beta-hydroxysteroid dehydrogenase-2 (11 beta-HSD2), which
      converts excess cortisol (F) to inactive cortisone (E). Impaired activity of this
      enzyme is common in intrauterine growth restriction and preeclampsia, conditions
      frequently associated with early preterm birth. To identify clinical determinants
      associated with decreased placental 11 beta-HSD2 function, we studied 107 small
      preterm infants [mean birth weight, 1067 g (range, 395-2453 g); gestational age,
      28.2 wk (range, 22.4-32.0 wk)] by determining their placental 11 beta-HSD2
      activity rate (per milligram protein) and total activity (per placenta) as well
      as cord vein F and E concentrations. An E/(E+ F) ratio expresses the overall
      balance of the F/E shuttle. There were positive correlations between relative
      birth weight and placental 11 beta-HSD2 activity rate (r = 0.30; P = 0.002) and
      total activity (r = 0.56; P < 0.0001) as well as E/(E+ F) ratio (r = 0.27; P =
      0.01) and E concentration (r = 0.32; P = 0.003). Infants with increased umbilical
      artery resistance had lower total placental 11 beta-HSD2 activity (P = 0.02),
      E/(E+ F) ratio (P = 0.04), and E concentration (P = 0.0002). Gestational age was
      inversely associated with placental 11 beta-HSD2 activity rate (r = -0.25; P =
      0.009). We conclude that, in small preterm infants, reduced placental 11 beta
      HSD2 function is associated with low relative birth weight and severe fetal
      distress. Whether these conditions are associated with early postnatal adrenal
      insufficiency or long-term cardiovascular risk remains an important issue for
      further study.

PMID- 12519894
TI  - Stromal cells of the human postmenopausal ovary display a distinctive biochemical
      and molecular phenotype.
AB  - The stroma of the human postmenopausal ovary is postulated to produce androgens,
      but evidence for and against this idea exits in the literature. The purpose of
      this study was to determine whether key steroidogenic enzymes involved in
      androgen synthesis are expressed in the postmenopausal ovarian stroma. Stromal
      cells were isolated from postmenopausal ovaries and expression for genes involved
      in steroidogenesis [steroidogenic acute regulatory protein (StAR), P450scc, 3
      beta-hydroxysteroid dehydrogenase (3 beta-HSD) P450c17, and P450c27] as well as
      for several growth factor binding proteins [gremlin, IGF binding protein-4,
      follistatin, and secreted frizzled-related protein (sFRP)-1 and -4], were
      compared with cultured human theca cells and dermal fibroblasts. Production of
      steroids (pregnenolone, progesterone, and hydroxysterol metabolites) and the
      metabolism of [3H] pregnenolone by ovarian stromal cells were also assessed.
      Isolated ovarian stromal cells from different subjects had a uniform morphology
      within and across cultures. Quantitative real time RT-PCR revealed that StAR,
      P450scc, and 3 beta-HSD transcripts were, respectively 30, 25, and 45 times more
      abundant in theca cells than in stromal cells. Mean levels of P450scc and 3 beta
      HSD transcripts in stromal cells were similar to those found in dermal
      fibroblasts, whereas StAR transcripts in stromal cells were 285-fold more
      abundant than in fibroblasts. There was no significant expression of P450c17 in
      ovarian stromal cells or fibroblasts ( approximately 2000-fold less than in theca
      cells). Western analysis demonstrated the presence of the 30-kDa StAR mature
      protein in the cultured stromal cells, whereas P450c17 protein was not
      detectable. Ovarian stromal cells did not metabolize [3H] pregnenolone in the
      presence or absence of 8-Br-cAMP. Furthermore, pregnenolone and progesterone
      secretion by stromal cells was also undetectable, even in the presence of 22
      hydroxycholesterol. P450c27 protein was detected in ovarian stromal cells and its
      metabolic products (i.e. 27-hydroxycholesterol and cholestenoic acid) were found
      in the culture media, reflecting functional cholesterol 27-hydroxylase activity.
      Follistatin, gremlin, IGF binding protein-4, and sFRP-1 and -4 transcripts were
      detected in the stromal cells in relative amounts significantly higher than theca
      cells, but not significantly different from fibroblasts, except for sFRP-1, which
      was significantly higher in stromal cells. Our observations demonstrate that
      stromal cells of the postmenopausal ovary have a signature biochemical and
      molecular phenotype that can be distinguished from fibroblasts. These cells do
      not appear to have significant steroidogenic potential in vitro, but they do
      metabolize cholesterol into hydroxysterols. We conclude that the predominant
      stromal cells of the postmenopausal ovary are not a significant site of androgen
      biosynthesis.

PMID- 12519896
TI  - Purification and characterization of a novel intracellular 17 beta-estradiol
      binding protein in estrogen-resistant New World primate cells.
AB  - Compared to Old World primates, including man, New World primates display target
      tissue resistance to gonadal steroid hormones. In female New World primates this
      resistant phenotype is characterized by elevated concentrations of plasma
      estradiol and progesterone. Here we describe the discovery of an intracellular
      estrogen binding protein (IEBP) that acts to concentrate 17 beta-estradiol (E2)
      in the cytoplasm of New World primate target cells. IEBP was purified by E2
      affinity chromatography from postnuclear extracts of the B95-8 cells established
      from an E2-resistant New World primate. Compared with unpurified extract,
      affinity-purified IEBP demonstrated a 300-fold enrichment in specific E2 binding
      activity; half-maximal displacement of [3H]E2 from affinity-purified IEBP was
      observed with 0.1 nM E2. Affinity-purified extracts were subjected to SDS-PAGE
      with isolation of a dominant 27-28 kDa protein. N-terminal sequencing of tryptic
      peptides of the protein showed sequence homology with human heat shock protein-27
      (hsp27). By immunoblot and E2 binding capacity, IEBP was 1] 2-3-fold greater in
      New World than in Old World primate tissues and cell lines, 2] heat-inducible and
      3] up-regulated in vivo in the presence of the functioning female gonad. In
      conclusion, IEBP is a specific E2-interacting heat shock protein in the hsp-27
      family that is relatively overexpressed in estrogen-resistant cells.

PMID- 12519897
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 12519898
TI  - National hormone & peptide program-NIDDK: recombinant hormones, hypothalamic
      peptides & other hormones, antisera, reagents, & hormone assay services
      available.

PMID- 12519899
TI  - Factors affecting the errors in the estimation of evolutionary distances between
      sequences.
AB  - Phylogenetic methods that use matrices of pairwise distances between sequences
      (e.g., neighbor joining) will only give accurate results when the initial
      estimates of the pairwise distances are accurate. For many different models of
      sequence evolution, analytical formulae are known that give estimates of the
      distance between two sequences as a function of the observed numbers of
      substitutions of various classes. These are often of a form that we call "log
      transform formulae". Errors in these distance estimates become larger as the time
      t since divergence of the two sequences increases. For long times, the log
      transform formulae can sometimes give divergent distance estimates when applied
      to finite sequences. We show that these errors become significant when t
      approximately 1/2 |lambda(max)|(-1) logN, where lambda(max) is the eigenvalue of
      the substitution rate matrix with the largest absolute value and N is the
      sequence length. Various likelihood-based methods have been proposed to estimate
      the values of parameters in rate matrices. If rate matrix parameters are known
      with reasonable accuracy, it is possible to use the maximum likelihood method to
      estimate evolutionary distances while keeping the rate parameters fixed. We show
      that errors in distances estimated in this way only become significant when t
      approximately 1/2 |lambda(1)|(-1) logN, where lambda(1) is the eigenvalue of the
      substitution rate matrix with the smallest nonzero absolute value. The accuracy
      of likelihood-based distance estimates is therefore much higher than those based
      on log transform formulae, particularly in cases where there is a large range of
      timescales involved in the rate matrix (e.g., when the ratio of transition to
      transversion rates is large). We discuss several practical ways of estimating the
      rate matrix parameters before distance calculation and hence of increasing the
      accuracy of distance estimates.

PMID- 12519900
TI  - Partitioning the variation in mammalian substitution rates.
AB  - We have used analysis of variance to partition the variation in synonymous and
      amino acid substitution rates between three effects (gene, lineage, and a gene-by
      lineage interaction) in mammalian nuclear and mitochondrial genes. We find that
      gene effects are stronger for amino acid substitution rates than for synonymous
      substitution rates and that lineage effects are stronger for synonymous
      substitution rates than for amino acid substitution rates. Gene-by-lineage
      interactions, equivalent to overdispersion corrected for lineage effects, are
      found in amino acid substitutions but not in synonymous substitutions. The
      variance in the ratio of amino acid and synonymous substitution rates is
      dominated by gene effects, but there is also a significant gene-by-lineage
      interaction.

PMID- 12519901
TI  - Pervasive adaptive evolution in mammalian fertilization proteins.
AB  - Mammalian fertilization exhibits species specificity, and the proteins mediating
      sperm-egg interactions evolve rapidly between species. In this study, we
      demonstrate that the evolution of seven genes involved in mammalian fertilization
      is promoted by positive Darwinian selection by using likelihood ratio tests
      (LRTs). Several of these proteins are sperm proteins that have been implicated in
      binding the mammalian egg coat zona pellucida glycoproteins, which were shown
      previously to be subjected to positive selection. Taken together, these represent
      the major candidates involved in mammalian fertilization, indicating positive
      selection is pervasive amongst mammalian reproductive proteins. A new LRT is
      implemented to determine if the d(N)/d(S) ratio is significantly greater than
      one. This is a more refined test of positive selection than the previous LRTs
      which only identified if there was a class of sites with a d(N)/d(S) ratio >1 but
      did not test if that ratio was significantly greater than one.

PMID- 12519902
TI  - Positive selection within sperm-egg adhesion domains of fertilin: an ADAM gene
      with a potential role in fertilization.
AB  - Genes with a role in fertilization show a common pattern of rapid evolution. The
      role played by positive selection versus lack of selective constraints has been
      more difficult to establish. One problem arises from attempts to detect selection
      in an overall gene sequence analysis. I have analyzed the pattern of molecular
      evolution of fertilin, a gene coding for a heterodimeric sperm protein belonging
      to the ADAM (A disintegrin and A metalloprotease) gene family. A nonsynonymous to
      synonymous rate ratio (d(N)/d(S)) analysis for different protein domains of
      fertilin alpha and fertilin beta showed d(N)/d(S) < 1, suggesting that purifying
      selection has shaped fertilin's evolution. However, an analysis of the
      distribution of single positively selected codon sites using phylogentic analysis
      by maximum likelihood (PAML) showed sites within adhesion domains (disintegrin
      and cysteine-rich) of fertilin beta evolving under positive selection. The region
      3' to the EGF-like domain of fertilin alpha, where the transmembrane and
      cytoplasmic tail regions are supposed to be localized, showed higher d(N) and
      d(S) than any other fertilin alpha region. However, it was not possible to
      identify positively selected codon sites due to ambiguous alignments of the
      carboxy-end region (ClustalX vs. DiAlign2). When this region was excluded from
      the PAML analysis, most single positively selected codon sites were concentrated
      within adhesion domains (cysteine-rich and EGF-like). The use of an ancestral
      sequence prior to a recent duplication event of fertilin alpha among non
      Hominidae primates (Macaca, Papio, and Saguinus) revealed that the duplication is
      partially responsible for masking the detection of positively selected sites
      within the disintegrin domain. Finally, most ADAM genes with a potential role in
      sperm maturation and/or fertilization showed significantly higher d(N) estimates
      than other ADAM genes.

PMID- 12519903
TI  - Transiently beneficial insertions could maintain mobile DNA sequences in variable
      environments.
AB  - The maintenance of mobile DNA sequences in clonal organisms has been seen as a
      paradox. If selfish mobile sequences spread through genomes only by
      overreplication in transposition, then sexuality is necessary for their spread
      through populations. The persistence of bacterial transposable elements without
      obvious dominant selectable markers has previously been explained by horizontal
      transfer. However, advantageous insertions of mobile DNAs are known in bacteria.
      Here we model maintenance of an otherwise selfish mobile DNA element in a clonal
      species in which selection for null mutations occurs during one of two temporally
      alternating environments. Large areas of parameter space permit maintenance of
      mobile DNAs where, without selection, they would have gone extinct. Horizontal
      transfer diminishes, rather than enhances, mean copy number. In finite
      populations, effective population sizes are greatly reduced by selective sweeps,
      and mean copy number can be increased as the reduced variance in copy number
      results in reduced selection.

PMID- 12519904
TI  - The esterase and PHD domains in CR1-like non-LTR retrotransposons.
AB  - Most active non-LTR (long terminal repeat) retrotransposons carry two open
      reading frames (ORFs) encoding ORF1p and ORF2p proteins. The ORF2p proteins are
      relatively well studied and are known to contain endonuclease/reverse
      transcriptase domains. At the same time, the biological function of ORF1p
      proteins remains poorly understood, except in that they nonspecifically bind
      single-stranded mRNA/DNA molecules. CR1-like elements form the most widely
      distributed clade/superfamily of non-LTR retrotransposons. We found that ORF1p
      proteins encoded by diverse CR1-like elements contain conserved esterase domain
      (ES) or plant homeodomain (PHD). This indicates that CR1-like ORF1p proteins are
      either lipolytic enzymes or are involved in protein-protein interactions related
      to chromatin remodeling. Sequence conservation of ES suggests that interaction
      with cellular membranes is an important phase in life circles of CR1-like
      elements. Presumably such interaction helps in penetrating host cells. As a
      consequence, the presence of multiple young CR1 families characterized by
      approximately 10% intrafamily and 40% interfamily identities may be explained by
      a relatively frequent horizontal transfer of these CR1-like elements.
      Unexpectedly, ES links together non-LTR retrotransposons and single-stranded RNA
      viruses like influenza C and coronaviruses, which are known to depend on their
      own ES.

PMID- 12519905
TI  - A low rate of simultaneous double-nucleotide mutations in primates.
AB  - The occurrence of double-nucleotide (doublet) mutations is contrary to the normal
      assumption that point mutations affect single nucleotides. Here we develop a new
      method for estimating the doublet mutation rate and apply it to more than a
      megabase of human-chimpanzee-baboon genomic DNA alignments and more than a
      million human single-nucleotide polymorphisms. The new method accounts for the
      effect of regional variation in evolutionary rates, which may be a confounding
      factor in previous estimates of the doublet mutation rate. Furthermore we
      determine sequence context effects by using sequence comparisons over a variety
      of lineage lengths. This approach yields a new estimate of the doublet mutation
      rate of 0.3% of the singleton rate, indicating that doublet mutations are far
      rarer than previously thought. Our results suggest that doublet mutations are
      unlikely to have caused the correlation between synonymous and nonsynonymous
      substitution rates in mammals, and also show that regional variation and sequence
      context effects play an important role in primate DNA sequence evolution.

PMID- 12519906
TI  - Microsatellite evolution at two hypervariable loci revealed by extensive avian
      pedigrees.
AB  - Genealogies generated through a long-term study of superb fairy-wrens (Malurus
      cyaneus) were used to investigate mutation within two hypervariable
      microsatellite loci. Of 3,230 meioses examined at the tetranucleotide locus (Mcy
      micro 8), 45 mutations were identified, giving a mutation rate of 1.4%. At the
      dinucleotide locus (Mcy micro 4) 30 mutations were recorded from 2,750 meioses
      giving a mutation rate of 1.1%. Mutations at both loci primarily (80%; 60/75)
      involved the loss or gain of a single repeat unit. Unlike previous studies, there
      was no significant bias toward additions over deletions. The mutation rate at Mcy
      micro 8 increased with allele size, and very long alleles (>70 repeats) mutated
      at a rate of almost 20%. The length of the mutating allele and allele span,
      however, were strongly correlated so it was not possible to isolate the causative
      factor. Allele size did not appear to affect mutation rate at Mcy micro 4, but
      the repeat number was considerably lower at this locus. The gender of the
      mutating parent was significant only at Mcy micro 8, where mutations occurred
      more frequently in maternal alleles. However, at both loci we found that alleles
      inherited from the mother were on average larger than those from the father, and
      this in part drove the higher mutation rate among maternally inherited alleles at
      Mcy micro 8.

PMID- 12519907
TI  - A novel polyubiquitin structure in Cercozoa and Foraminifera: evidence for a new
      eukaryotic supergroup.
AB  - Ubiquitin is a 76 amino acid protein with a remarkable degree of evolutionary
      conservation. Ubiquitin plays an essential role in a large number of eukaryotic
      cellular processes by targeting proteins for proteasome-mediated degradation.
      Most ubiquitin genes are found as head-to-tail polymers whose products are
      posttranslationally processed to ubiquitin monomers. We have characterized
      polyubuiquitin genes from the photosynthetic amoeboflagellate Chlorarachnion sp.
      CCMP 621 (also known as Bigelowiella natans) and found that they deviate from the
      canonical polyubiquitin structure in having an amino acid insertion at the
      junction between each monomer, suggesting that polyubiquitin processing in this
      organism is unique among eukaryotes. The gene structure indicates that processing
      likely cleaves monomers at the amino terminus of the insertion. We examined the
      phylogenetic distribution of the insertion by sequencing polyubiquitin genes from
      several other eukaryotic groups and found it to be confined to Cercozoa
      (including Chlorarachnion, Lotharella, Cercomonas, and Euglypha) and Foraminifera
      (including Reticulomyxa and Haynesina). This character strongly suggests that
      Cercozoa and Foraminifera are close relatives and form a new "supergroup" of
      eukaryotes.

PMID- 12519908
TI  - Polyphyletic origin of cultivated rice: based on the interspersion pattern of
      SINEs.
AB  - The wild rice species Oryza rufipogon with wide intraspecific variation is
      thought to be the progenitor of the cultivated rice species Oryza sativa with two
      ecotypes, japonica and indica. To determine the origin of cultivated rice,
      subfamily members of the rice retroposon p-SINE1, which show insertion
      polymorphism in the O. sativa -O. rufipogon population, were identified and used
      to "bar code" each of 101 cultivated and wild rice strains based on the presence
      or absence of the p-SINE1 members at the respective loci. A phylogenetic tree
      constructed based on the bar codes given to the rice strains showed that O.
      sativa strains were classified into two groups corresponding to japonica and
      indica, whereas O. rufipogon strains were in four groups, in which annual O.
      rufipogon strains formed a single group, differing from the perennial O.
      rufipogon strains of the other three groups. Japonica strains were closely
      related to the O. rufipogon perennial strains of one group, and the indica
      strains were closely related to the O. rufipogon annual strains, indicating that
      O. sativa has been derived polyphyletically from O. rufipogon. The subfamily
      members of p-SINE1 constitute a powerful tool for studying the classification and
      relationship of rice strains, even when one has limited knowledge of morphology,
      taxonomy, physiology, and biochemistry of rice strains.

PMID- 12519909
TI  - Intra-deme molecular diversity in spatially expanding populations.
AB  - We report here a simulation study examining the effect of a recent spatial
      expansion on the pattern of molecular diversity within a deme. We first simulate
      a range expansion in a virtual world consisting in a two-dimensional array of
      demes exchanging a given proportion of migrants (m) with their neighbors. The
      recorded demographic and migration histories are then used under a coalescent
      approach to generate the genetic diversity in a sample of genes. We find that the
      shape of the gene genealogies and the overall pattern of diversity within demes
      depend not only on the age of the expansion but also on the level of gene flow
      between neighboring demes, as measured by the product Nm, where N is the size of
      a deme. For small Nm values (< approximately 20 migrants sent outwards per
      generation), a substantial proportion of coalescent events occur early in the
      genealogy, whereas with larger levels of gene flow, most coalescent events occur
      around the time of the onset of the spatial expansion. Gene genealogies are star
      shaped, and mismatch distributions are unimodal after a range expansion for large
      Nm values. In contrast, gene genealogies present a mixture of both very short and
      very long branch lengths, and mismatch distributions are multimodal for small Nm
      values. It follows that statistics used in tests of selective neutrality like
      Tajima's D statistic or Fu's F(S) statistic will show very significant negative
      values after a spatial expansion only in demes with high Nm values. In the
      context of human evolution, this difference could explain very simply the fact
      that analyses of samples of mitochondrial DNA sequences reveal multimodal
      mismatch distributions in hunter-gatherers and unimodal distributions in post
      Neolithic populations. Indeed, the current simulations show that a recent
      increase in deme size (resulting in a larger Nm value) is sufficient to prevent
      recent coalescent events and thus lead to unimodal mismatch distributions, even
      if deme sizes (and therefore Nm values) were previously much smaller. The fact
      that molecular diversity within deme is so dependent on recent levels of gene
      flow suggests that it should be possible to estimate Nm values from samples drawn
      from a single deme.

PMID- 12519910
TI  - Evolution and phylogenetic utility of alignment gaps within intron sequences of
      three nuclear genes in bumble bees (Bombus).
AB  - To test whether gaps resulting from sequence alignment contain phylogenetic
      signal concordant with those of base substitutions, we analyzed the occurrence of
      indel mutations upon a well-resolved, substitution-based tree for three nuclear
      genes in bumble bees (Bombus, Apidae: Bombini). The regions analyzed were exon
      and intron sequences of long-wavelength rhodopsin (LW Rh), arginine kinase
      (ArgK), and elongation factor-1alpha (EF-1alpha) F2 copy genes. LW Rh intron had
      only a few uninformative gaps, ArgK intron had relatively long gaps that were
      easily aligned, and EF-1alpha intron had many short gaps, resulting in multiple
      optimal alignments. The unambiguously aligned gaps within ArgK intron sequences
      showed no homoplasy upon the substitution-based tree, and phylogenetic signals
      within ambiguously aligned regions of EF-1alpha intron were highly congruent with
      those of base substitutions. We further analyzed the contribution of gap
      characters to phylogenetic reconstruction by incorporating them in parsimony
      analysis. Inclusion of gap characters consistently improved support for nodes
      recovered by substitutions, and inclusion of ambiguously aligned regions of EF
      1alpha intron resolved several additional nodes, most of which were apical on the
      phylogeny. We conclude that gaps are an exceptionally reliable source of
      phylogenetic information that can be used to corroborate and refine phylogenies
      hypothesized by base substitutions, at least at lower taxonomic levels. At
      present, full use of gaps in phylogenetic reconstruction is best achieved in
      parsimony analysis, pending development of well-justified and generally
      applicable methods for incorporating indels in explicitly model-based methods.

PMID- 12519911
TI  - Evolution of the bacterial species Lactobacillus delbrueckii: a partial genomic
      study with reflections on prokaryotic species concept.
AB  - The species Lactobacillus delbrueckii consists at present of three subspecies,
      delbrueckii, lactis and bulgaricus, showing a high level of DNA-DNA hybridization
      similarity but presenting markedly different traits related to distinct
      ecological adaptation. The internal genetic heterogeneity of the bacterial
      species L. delbrueckii was analyzed. Phenotypic and several genetic traits were
      investigated for 61 strains belonging to this species. These included 16S rDNA
      sequence mutations, expression of beta-galactosidase and of the cell wall
      anchored protease, the characterization of the lactose operon locus and of the
      sequence of lacR gene, galactose metabolism, and the distribution of insertion
      sequences. The high genetic heterogeneity of taxa was confirmed by every trait
      investigated: the lac operon was completely deleted in the subsp. delbrueckii,
      different mutation events in the repressor gene of the operon led to a
      constitutive expression of lacZ in the subsp. bulgaricus. Structural differences
      in the same genetic locus were probably due to the presence of different IS
      elements in the flanking regions. The different expression of the cell wall
      anchored protease, constitutive in the subsp. bulgaricus, inducible in the subsp.
      lactis, and absent in the subsp. delbrueckii was also a consequence of mutations
      at the gene level. The galT gene for galactose metabolism was found only in the
      subsp. lactis, while no specific amplification product was detected in the other
      two subspecies. All these data, together with the absence of a specific IS
      element, ISL6, from the major number of strains belonging to the subsp.
      bulgaricus, confirmed a deep internal heterogeneity among the three subspecies.
      Moreover, this evidence and the directional mutations found in the 16S rDNA
      sequences suggested that, of the three subspecies, L. delbrueckii subsp. lactis
      is the taxon closer to the ancestor. Limitations of the current prokaryotic
      species definition were also discussed, based on presented evidences. Our results
      indicate the need for an accurate investigation of internal heterogeneity of
      bacterial species. This study has consequences on the prokaryotic species
      concept, since genomic flexibility of prokaryotes collides with a stable
      classification, necessary from a scientific and applied point of view.

PMID- 12519912
TI  - Base compositions of genes encoding alpha-actin and lactate dehydrogenase-A from
      differently adapted vertebrates show no temperature-adaptive variation in G + C
      content.
AB  - There is a long-standing debate in molecular evolution concerning the putative
      importance of GC content in adapting the thermal stabilities of DNA and RNA. Most
      studies of this relationship have examined broad-scale compositional patterns,
      for example, total GC percentages in genomes and occurrence of GC-rich isochores.
      Few studies have systematically examined the GC contents of individual
      orthologous genes from differently thermally adapted species. When this has been
      done, the emphasis has been on comparing large numbers of genes in only a few
      species. We have approached the GC-adaptation temperature hypothesis in a
      different manner by examining patterns of base composition of genes encoding
      lactate dehydrogenase-A (ldh-a) and alpha-actin (alpha-actin) from 51 species of
      vertebrates whose adaptation temperatures ranged from -1.86 degrees C (Antarctic
      fishes) to approximately 45 degrees C (desert reptile). No significant positive
      correlation was found between any index of GC content (GC content of the entire
      sequence, GC content of the third codon position [GC(3)], and GC content at
      fourfold degenerate sites [GC(4)]) and any index of adaptation temperature
      (maximal, mean, or minimal body temperature). For alpha-actin, slopes of
      regression lines for all comparisons did not differ significantly from zero. For
      ldh-a, negative correlations between adaptation temperature and total GC content,
      GC(3), and GC(4) were observed but were shown to be due entirely to phylogenetic
      influences (as revealed by independent contrast analyses). This comparison of GC
      content across a wide range of ectothermic ("cold-blooded") and endothermic
      ("warm-blooded") vertebrates revealed that frogs of the genus Xenopus, which have
      commonly been used as a representative cold-blooded species, in fact are outliers
      among ectotherms for the alpha-actin analyses, raising concern about the
      appropriateness of choosing these amphibians as representative of ectothermic
      vertebrates in general. Our study indicates that, whereas GC contents of
      isochores may show variation among different classes of vertebrates, there is no
      consistent relationship between adaptation temperature and the percentage of
      thermal stability-enhancing G + C base pairs in protein-coding genes.

PMID- 12519913
TI  - Molecular evolution of the mammalian prion protein.
AB  - Prion protein (PrP) sequences are until now available for only six of the 18
      orders of placental mammals. A broader comparison of mammalian prions might help
      to understand the enigmatic functional and pathogenic properties of this protein.
      We therefore determined PrP coding sequences in 26 mammalian species to include
      all placental orders and major subordinal groups. Glycosylation sites, cysteines
      forming a disulfide bridge, and a hydrophobic transmembrane region are perfectly
      conserved. Also, the sequences responsible for secondary structure elements, for
      N- and C-terminal processing of the precursor protein, and for attachment of the
      glycosyl-phosphatidylinositol membrane anchor are well conserved. The N-terminal
      region of PrP generally contains five or six repeats of the sequence P(Q/H)GGG(G/
      )WGQ, but alleles with two, four, and seven repeats were observed in some
      species. This suggests, together with the pattern of amino acid replacements in
      these repeats, the regular occurrence of repeat expansion and contraction.
      Histidines implicated in copper ion binding and a proline involved in 4
      hydroxylation are lacking in some species, which questions their importance for
      normal functioning of cellular PrP. The finding in certain species of two or
      seven repeats, and of amino acid substitutions that have been related to human
      prion diseases, challenges the relevance of such mutations for prion pathology.
      The gene tree deduced from the PrP sequences largely agrees with the species
      tree, indicating that no major deviations occurred in the evolution of the prion
      gene in different placental lineages. In one species, the anteater, a prion
      pseudogene was present in addition to the active gene.

PMID- 12519914
TI  - Inferring the rate and time-scale of dengue virus evolution.
AB  - Dengue is often referred to as an emerging disease because of the rapid increases
      in incidence and prevalence that have been observed in recent decades. To
      understand the rate at which genetic diversification occurs in dengue virus and
      to infer the time-scale of its evolution, we employed a maximum likelihood method
      that uses information about times of virus sampling to estimate the rate of
      molecular evolution in a large number of viral envelope (E) gene sequences and to
      place bounds around the dates of appearance of all serotypes and specific
      genotypes. Our analysis reveals that dengue virus generally evolves according to
      a molecular clock, although some serotype-specific and genotype-specific rate
      differences were observed, and that its origin is more recent than previously
      suggested, with the virus appearing approximately 1,000 years ago. Furthermore,
      we estimate that the zoonotic transfer of dengue from sylvatic (monkey) to
      sustained human transmission occurred between 125 and 320 years ago, that the
      current global genetic diversity in the four serotypes of dengue virus only
      appeared during the past century, and that the recent rise in genetic diversity
      can be loosely correlated both to human activities such as population growth,
      urbanization, and mass transport and to the emergence of dengue hemorrhagic fever
      as a major disease problem.

PMID- 12519915
TI  - Placozoa are not derived cnidarians: evidence from molecular morphology.
AB  - The phylum Placozoa is represented by a single known species, Trichoplax
      adhaerens, a tiny marine organism that represents the most simple metazoan
      bauplan. Because of the latter, placozoans were originally considered the most
      basal metazoan phylum. A misinterpretation of the life cycle at the turn of the
      century and some more recent molecular phylogenetic analyses have placed
      Trichoplax as a derived species within the Cnidaria. The latter hypothesis
      assumes that the primitive organization of the Placozoa is the result of
      secondary reduction. Here we compare the molecular morphology of the predicted
      16S rDNA structure and the mitochondrial genome between Trichoplax and
      representatives of all four cnidarian classes. Trichoplax shares a circular mtDNA
      molecule as a plesiomorphy with all other metazoans except for the derived
      cnidarian classes Hydrozoa, Scyphozoa, and Cubozoa. The predicted secondary
      structure of the 16S rRNA molecule differs substantially between Trichoplax and
      cnidarians, particularly with respect to the number and length of stem and loop
      regions. The new molecular morphological characters provide compelling evidence
      that Trichoplax is not a derived (medusozoan) cnidarian. Furthermore, it was
      found that the mitochondrial genome in Cubozoa consists of four linear molecules
      instead of a single circular molecule or two linear molecules, suggesting that
      the cubozoans may represent the most derived cnidarian group.

PMID- 12519916
TI  - Modification of heat-shock gene expression in Drosophila melanogaster populations
      via transposable elements.
AB  - We report multiple cases in which disruption of hsp70 regulatory regions by
      transposable element (TE) insertions underlies natural variation in expression of
      the stress-inducible molecular chaperone Hsp70 in Drosophila melanogaster. Three
      D. melanogaster populations from different continents are polymorphic for jockey
      or P element insertions in the promoter of the hsp70Ba gene. All three TE
      insertions are within the same 87-bp region of hsp70Ba promoter, and we suggest
      that the distinctive promoter architecture of hsp genes may make them vulnerable
      to TE insertions. Each of the TE insertions reduces Hsp70 levels, and RNase
      protection assays demonstrate that such insertions can reduce transcription of
      the hsp70Ba gene. In addition, the TEs alter two measures of organismal fitness,
      inducible thermotolerance and female reproductive success. Thus, transposition
      can create quantitative genetic variation in gene expression within populations,
      on which natural selection can act.

PMID- 12519917
TI  - Structure of the bc1 complex from Seculamonas ecuadoriensis, a jakobid flagellate
      with an ancestral mitochondrial genome.
AB  - In eubacteria, the respiratory bc(1) complex (complex III) consists of three or
      four different subunits, whereas that of mitochondria, which have descended from
      an alpha-proteobacterial endosymbiont, contains about seven additional subunits.
      To understand better how mitochondrial protein complexes evolved from their
      simpler bacterial predecessors, we purified complex III of Seculamonas
      ecuadoriensis, a member of the jakobid protists, which possess the most bacteria
      like mitochondrial genomes known. The S. ecuadoriensis complex III has an
      apparent molecular mass of 460 kDa and exhibits antimycin-sensitive
      quinol:cytochrome c oxidoreductase activity. It is composed of at least eight
      subunits between 6 and 46 kDa in size, including two large "core" subunits and
      the three "respiratory" subunits. The molecular mass of the S. ecuadoriensis
      bc(1) complex is slightly lower than that reported for other eukaryotes, but
      about 2x as large as complex III in bacteria. This indicates that the departure
      from the small bacteria-like complex III took place at an early stage in
      mitochondrial evolution, prior to the divergence of jakobids. We posit that the
      recruitment of additional subunits in mitochondrial respiratory complexes is a
      consequence of the migration of originally alpha-proteobacterial genes to the
      nucleus.

PMID- 12519918
TI  - The temporal distribution of gene duplication events in a set of highly conserved
      human gene families.
AB  - Using a data set of protein translations associated with map positions in the
      human genome, we identified 1520 mapped highly conserved gene families. By
      comparing sharing of families between genomic windows, we identified 92
      potentially duplicated blocks in the human genome containing 422 duplicated
      members of these families. Using branching order in the phylogenetic trees, we
      timed gene duplication events in these families relative to the primate-rodent
      divergence, the amniote-amphibian divergence, and the deuterostome-protostome
      divergence. The results showed similar patterns of gene duplication times within
      duplicated blocks and outside duplicated blocks. Both within and outside
      duplicated blocks, numerous duplications were timed prior to the deuterostome
      protostome divergence, whereas others occurred after the amniote-amphibian
      divergence. Thus, neither gene duplication in general nor duplication of genomic
      blocks could be attributed entirely to polyploidization early in vertebrate
      history. The strongest signal in the data was a tendency for intrachromosomal
      duplications to be more recent than interchromosomal duplications, consistent
      with a model whereby tandem duplication-whether of single genes or of genomic
      blocks-may be followed by eventual separation of duplicates due to chromosomal
      rearrangements. The rate of separation of tandemly duplicated gene pairs onto
      separated chromosomes in the human lineage was estimated at 1.7 x 10(-9) per gene
      pair per year.

PMID- 12519919
TI  - Is microanatomy destiny?

PMID- 12519920
TI  - Nephron number in patients with primary hypertension.
AB  - BACKGROUND: A diminished number of nephrons has been proposed as one of the
      factors contributing to the development of primary hypertension. METHODS: To test
      this hypothesis, we used a three-dimensional stereologic method to compare the
      number and volume of glomeruli in 10 middle-aged white patients (age range, 35 to
      59 years) with a history of primary hypertension or left ventricular hypertrophy
      (or both) and renal arteriolar lesions with the number and volume in 10
      normotensive subjects matched for sex, age, height, and weight. All 20 subjects
      had died in accidents. RESULTS: Patients with hypertension had significantly
      fewer glomeruli per kidney than matched normotensive controls (median, 702,379
      vs. 1,429,200). Patients with hypertension also had a significantly greater
      glomerular volume than did the controls (median, 6.50x10(-3) mm3 vs. 2.79x10(-3)
      mm3; P<0.001) but very few obsolescent glomeruli. CONCLUSIONS: The data support
      the hypothesis that the number of nephrons is reduced in white patients with
      primary hypertension.

PMID- 12519921
TI  - Roles of drinking pattern and type of alcohol consumed in coronary heart disease
      in men.
AB  - BACKGROUND: Although moderate drinking confers a decreased risk of myocardial
      infarction, the roles of the drinking pattern and type of beverage remain
      unclear. METHODS: We studied the association of alcohol consumption with the risk
      of myocardial infarction among 38,077 male health professionals who were free of
      cardiovascular disease and cancer at base line. We assessed the consumption of
      beer, red wine, white wine, and liquor individually every four years using
      validated food-frequency questionnaires. We documented cases of nonfatal
      myocardial infarction and fatal coronary heart disease from 1986 to 1998.
      RESULTS: During 12 years of follow-up, there were 1418 cases of myocardial
      infarction. As compared with men who consumed alcohol less than once per week,
      men who consumed alcohol three to four or five to seven days per week had
      decreased risks of myocardial infarction (multivariate relative risk, 0.68 [95
      percent confidence interval, 0.55 to 0.84] and 0.63 [95 percent confidence
      interval, 0.54 to 0.74], respectively). The risk was similar among men who
      consumed less than 10 g of alcohol per drinking day and those who consumed 30 g
      or more. No single type of beverage conferred additional benefit, nor did
      consumption with meals. A 12.5-g increase in daily alcohol consumption over a
      four-year follow-up period was associated with a relative risk of myocardial
      infarction of 0.78 (95 percent confidence interval, 0.62 to 0.99). CONCLUSIONS:
      Among men, consumption of alcohol at least three to four days per week was
      inversely associated with the risk of myocardial infarction. Neither the type of
      beverage nor the proportion consumed with meals substantially altered this
      association. Men who increased their alcohol consumption by a moderate amount
      during follow-up had a decreased risk of myocardial infarction.

PMID- 12519922
TI  - Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.
AB  - BACKGROUND: Despite the prevalence of multidrug-resistant tuberculosis in nearly
      all low-income countries surveyed, effective therapy has been deemed too
      expensive and considered not to be feasible outside referral centers. We
      evaluated the results of community-based therapy for multidrug-resistant
      tuberculosis in a poor section of Lima, Peru. METHODS: We describe the first 75
      patients to receive ambulatory treatment with individualized regimens for chronic
      multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective
      review of the charts of all patients enrolled in the program between August 1,
      1996, and February 1, 1999, and identified predictors of poor outcomes. RESULTS:
      The infecting strains of Mycobacterium tuberculosis were resistant to a median of
      six drugs. Among the 66 patients who completed four or more months of therapy, 83
      percent (55) were probably cured at the completion of treatment. Five of these 66
      patients (8 percent) died while receiving therapy. Only one patient continued to
      have positive cultures after six months of treatment. All patients in whom
      treatment failed or who died had extensive bilateral pulmonary disease. In a
      multiple Cox proportional-hazards regression model, the predictors of the time to
      treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent
      confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio,
      3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide
      and ethambutol in the regimen (when susceptibility was confirmed) was associated
      with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95
      percent confidence interval, 0.11 to 0.83). CONCLUSIONS: Community-based
      outpatient treatment of multidrug-resistant tuberculosis can yield high cure
      rates even in resource-poor settings. Early initiation of appropriate therapy can
      preserve susceptibility to first-line drugs and improve treatment outcomes.

PMID- 12519923
TI  - Images in clinical medicine. Page kidney.

PMID- 12519924
TI  - Trends in care by nonphysician clinicians in the United States.
AB  - BACKGROUND: The 1990s saw rising numbers of graduates of training programs for
      nonphysician clinicians, passage of legislation expanding their scope of
      practice, and a proliferation of managed-care models that emphasized the use of
      these providers as a strategy for containing health care costs. METHODS: We used
      two nationally representative surveys to examine trends in outpatient care
      provided by physicians and nonphysician clinicians between 1987 and 1997,
      adjusting for the case mix. Analyses examined care provided by 10 categories of
      nonphysician clinicians: chiropractors, midwives, nurses or nurse practitioners,
      optometrists, podiatrists, physician assistants, physical or occupational
      therapists, psychologists, social workers, and others. RESULTS: Between 1987 and
      1997, the proportion of patients who saw a nonphysician clinician rose from 30.6
      percent to 36.1 percent (adjusted relative risk for 1997 as compared with 1987,
      1.42 [95 percent confidence interval, 1.35 to 1.50]). The trend was driven by an
      increase in the proportion of persons who visited both a physician and a
      nonphysician clinician (from 23.5 percent to 30.9 percent; adjusted relative
      risk, 1.49 [95 percent confidence interval, 1.40 to 1.58]), rather than an
      increase in the proportion who saw only a nonphysician clinician (from 7.2
      percent to 5.3 percent; adjusted relative risk, 0.81 [95 percent confidence
      interval, 0.70 to 0.93]). This pattern was consistent in analyses of specific
      medical conditions and specific types of nonphysician clinicians. There was an
      increase in the proportion of patients obtaining preventive services from
      nonphysician clinicians and a decline in the proportion receiving acute care
      services from such clinicians. CONCLUSIONS: From 1987 to 1997, there was a degree
      of differentiation between physicians and nonphysician clinicians with respect to
      the services they provided but not with respect to the patients they treated. The
      implications of these findings hinge on the degree to which the increase in
      conjoint service delivery represents growing coordination or fragmentation of
      care.

PMID- 12519925
TI  - The pathophysiology and treatment of sepsis.

PMID- 12519926
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-2003. A 43-year-old man with fever and night sweats.

PMID- 12519927
TI  - To drink or not to drink?

PMID- 12519928
TI  - Achieving an interdisciplinary workforce in health care.

PMID- 12519929
TI  - Complement C5a in the sepsis syndrome--too much of a good thing?

PMID- 12519930
TI  - Prostatectomy or watchful waiting in prostate cancer.

PMID- 12519931
TI  - Endotoxin and asthma.

PMID- 12519932
TI  - Mammographic density of the breast.

PMID- 12519933
TI  - Respiratory protection.

PMID- 12519934
TI  - Case 28-2002: a traveler with a rapidly progressive soft-tissue infection.

PMID- 12519935
TI  - Tenofovir disoproxil fumarate in patients with HIV and lamivudine-resistant
      hepatitis B virus.

PMID- 12519936
TI  - Hepatitis C virus, human herpesvirus 8, and the development of plasma-cell
      leukemia.

PMID- 12519937
TI  - The Molecular Biology Database Collection: 2003 update.
AB  - The Molecular Biology Database Collection is an online resource listing key
      databases of value to the biological community. This Collection is intended to
      bring fellow scientists' attention to high-quality databases that are available
      throughout the world, rather than just be a lengthy listing of all available
      databases. As such, this up-to-date listing is intended to serve as the jumping
      off point from which to find specialized databases that may be of use in
      advancing biological research. The databases included in this Collection provide
      new value to the underlying data by virtue of curation, new data connections or
      other innovative approaches. Short, searchable summaries and updates for each of
      the databases included in this Collection are available through the Nucleic Acids
      Research Web site at http://nar.oupjournals.org.

PMID- 12519938
TI  - DNA Data Bank of Japan (DDBJ) in XML.
AB  - The DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) has collected and
      released more entries and bases than last year. This is mainly due to large-scale
      submissions from Japanese sequencing teams on mouse, rice, chimpanzee, nematoda
      and other organisms. The contributions of DDBJ over the past year are 17.3%
      (entries) and 10.3% (bases) of the combined outputs of the International
      Nucleotide Sequence Databases (INSD). Our complete genome sequence database,
      Genome Information Broker (GIB), has been improved by incorporating XML. It is
      now possible to perform a more sophisticated database search against the new GIB
      than the ordinary BLAST or FASTA search.

PMID- 12519939
TI  - The EMBL Nucleotide Sequence Database: major new developments.
AB  - The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl/) incorporates,
      organizes and distributes nucleotide sequences from all available public sources.
      The database is located and maintained at the European Bioinformatics Institute
      (EBI) near Cambridge, UK. In an international collaboration with DDBJ (Japan) and
      GenBank (USA), data are exchanged amongst the collaborating databases on a daily
      basis to achieve optimal synchronization. Webin is the preferred web-based
      submission system for individual submitters, while automatic procedures allow
      incorporation of sequence data from large-scale genome sequencing centres and
      from the European Patent Office (EPO). Database releases are produced quarterly.
      Network services allow free access to the most up-to-date data collection via
      FTP, Email and World Wide Web interfaces. EBI's Sequence Retrieval System (SRS)
      integrates and links the main nucleotide and protein databases plus many other
      specialized molecular biology databases. For sequence similarity searching, a
      variety of tools (e.g. Fasta, BLAST) are available which allow external users to
      compare their own sequences against the latest data in the EMBL Nucleotide
      Sequence Database and SWISS-PROT. All resources can be accessed via the EBI home
      page at http://www.ebi.ac.uk.

PMID- 12519940
TI  - GenBank.
AB  - GenBank (R) is a comprehensive sequence database that contains publicly available
      DNA sequences for more than 119 000 different organisms, obtained primarily
      through the submission of sequence data from individual laboratories and batch
      submissions from large-scale sequencing projects. Most submissions are made using
      the BankIt (web) or Sequin programs and accession numbers are assigned by GenBank
      staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and
      the DNA Data Bank of Japan helps ensure worldwide coverage. GenBank is accessible
      through NCBI's retrieval system, Entrez, which integrates data from the major DNA
      and protein sequence databases along with taxonomy, genome, mapping, protein
      structure and domain information, and the biomedical journal literature via
      PubMed. BLAST provides sequence similarity searches of GenBank and other sequence
      databases. Complete bimonthly releases and daily updates of the GenBank database
      are available by FTP. To access GenBank and its related retrieval and analysis
      services, go to the NCBI home page at: http://www.ncbi.nlm.nih.gov.

PMID- 12519941
TI  - Database resources of the National Center for Biotechnology.
AB  - In addition to maintaining the GenBank(R) nucleic acid sequence database, the
      National Center for Biotechnology Information (NCBI) provides data analysis and
      retrieval resources for the data in GenBank and other biological data made
      available through NCBI's Web site. NCBI resources include Entrez, PubMed, PubMed
      Central (PMC), LocusLink, the NCBITaxonomy Browser, BLAST, BLAST Link (BLink),
      Electronic PCR (e-PCR), Open Reading Frame (ORF) Finder, References Sequence
      (RefSeq), UniGene, HomoloGene, ProtEST, Database of Single Nucleotide
      Polymorphisms (dbSNP), Human/Mouse Homology Map, Cancer Chromosome Aberration
      Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker
      (MM), Evidence Viewer (EV), Clusters of Orthologous Groups (COGs) database,
      Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online
      Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the
      Conserved Domain Database (CDD), and the Conserved Domain Architecture Retrieval
      Tool (CDART). Augmenting many of the Web applications are custom implementations
      of the BLAST program optimized to search specialized data sets. All of the
      resources can be accessed through the NCBI home page at:
      http://www.ncbi.nlm.nih.gov.

PMID- 12519942
TI  - NCBI Reference Sequence project: update and current status.
AB  - The goal of the NCBI Reference Sequence (RefSeq) project is to provide the single
      best non-redundant and comprehensive collection of naturally occurring biological
      molecules, representing the central dogma. Nucleotide and protein sequences are
      explicitly linked on a residue-by-residue basis in this collection. Ideally all
      molecule types will be available for each well-studied organism, but the initial
      database collection pragmatically includes only those molecules and organisms
      that are most readily identified. Thus different amounts of information are
      available for different organisms at any given time. Furthermore, for some
      organisms additional intermediate records are provided when the genome sequence
      is not yet finished. The collection is supplied by NCBI through three distinct
      pipelines in addition to collaborations with community groups. The collection is
      curated on an ongoing basis. Additional information about the NCBI RefSeq project
      is available at http://www.ncbi.nih.gov/RefSeq/.

PMID- 12519943
TI  - Ensembl 2002: accommodating comparative genomics.
AB  - The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics
      framework to organise biology around the sequences of large genomes. It is a
      comprehensive source of stable automatic annotation of human, mouse and other
      genome sequences, available as either an interactive web site or as flat files.
      Ensembl also integrates manually annotated gene structures from external sources
      where available. As well as being one of the leading sources of genome
      annotation, Ensembl is an open source software engineering project to develop a
      portable system able to handle very large genomes and associated requirements.
      These range from sequence analysis to data storage and visualisation and
      installations exist around the world in both companies and at academic sites.
      With both human and mouse genome sequences available and more vertebrate
      sequences to follow, many of the recent developments in Ensembl have focusing on
      developing automatic comparative genome analysis and visualisation.

PMID- 12519944
TI  - The European Bioinformatics Institute's data resources.
AB  - As the amount of biological data grows, so does the need for biologists to store
      and access this information in central repositories in a free and unambiguous
      manner. The European Bioinformatics Institute (EBI) hosts six core databases,
      which store information on DNA sequences (EMBL-Bank), protein sequences (SWISS
      PROT and TrEMBL), protein structure (MSD), whole genomes (Ensembl) and gene
      expression (ArrayExpress). But just as a cell would be useless if it couldn't
      transcribe DNA or translate RNA, our resources would be compromised if each
      existed in isolation. We have therefore developed a range of tools that not only
      facilitate the deposition and retrieval of biological information, but also allow
      users to carry out searches that reflect the interconnectedness of biological
      information. The EBI's databases and tools are all available on our website at
      www.ebi.ac.uk.

PMID- 12519945
TI  - The UCSC Genome Browser Database.
AB  - The University of California Santa Cruz (UCSC) Genome Browser Database is an up
      to date source for genome sequence data integrated with a large collection of
      related annotations. The database is optimized to support fast interactive
      performance with the web-based UCSC Genome Browser, a tool built on top of the
      database for rapid visualization and querying of the data at many levels. The
      annotations for a given genome are displayed in the browser as a series of tracks
      aligned with the genomic sequence. Sequence data and annotations may also be
      viewed in a text-based tabular format or downloaded as tab-delimited flat files.
      The Genome Browser Database, browsing tools and downloadable data files can all
      be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu),
      which also contains links to documentation and related technical information.

PMID- 12519946
TI  - CORG: a database for COmparative Regulatory Genomics.
AB  - Sequence conservation in non-coding, upstream regions of orthologous genes from
      man and mouse is likely to reflect common regulatory DNA sites. Motivated by this
      assumption we have delineated a catalogue of conserved non-coding sequence blocks
      and provide the CORG-'COmparative Regulatory Genomics'-database. The data were
      computed based on statistically significant local suboptimal alignments of 15 kb
      regions upstream of the translation start sites of, currently, 10 793 pairs of
      orthologous genes. The resulting conserved non-coding blocks were annotated with
      EST matches for easier detection of non-coding mRNA and with hits to known
      transcription factor binding sites. CORG data are accessible from the ENSEMBL web
      site via a DAS service as well as a specially developed web service
      (http://corg.molgen.mpg.de) for query and interactive visualization of the
      conserved blocks and their annotation.

PMID- 12519947
TI  - MBGD: microbial genome database for comparative analysis.
AB  - MBGD is a workbench system for comparative analysis of completely sequenced
      microbial genomes. The central function of MBGD is to create an orthologous gene
      classification table using precomputed all-against-all similarity relationships
      among genes in multiple genomes. In MBGD, an automated classification algorithm
      has been implemented so that users can create their own classification table by
      specifying a set of organisms and parameters. This feature is especially useful
      when the user's interest is focused on some taxonomically related organisms. The
      created classification table is stored into the database and can be explored
      combining with the data of individual genomes as well as similarity relationships
      among genomes. Using these data, users can carry out comparative analyses from
      various points of view, such as phylogenetic pattern analysis, gene order
      comparison and detailed gene structure comparison. MBGD is accessible at
      http://mbgd.genome.ad.jp/.

PMID- 12519948
TI  - ParaDB: a tool for paralogy mapping in vertebrate genomes.
AB  - We present ParaDB (http://abi.marseille.inserm.fr/paradb/), a new database for
      large-scale paralogy studies in vertebrate genomes. We intended to collect all
      information (sequence, mapping and phylogenetic data) needed to map and detect
      new paralogous regions, previously defined as Paralogons. The AceDB database
      software was used to generate graphical objects and to organize data. General
      data were automatically collated from public sources (Ensembl, GadFly and
      RefSeq). ParaDB provides access to data derived from whole genome sequences (Homo
      sapiens, Mus musculus and Drosophila melanogaster): cDNA and protein sequences,
      positional information, bibliographical links. In addition, we provide BLAST
      results for each protein sequence, InParanoid orthologs and 'In-Paralogs' data,
      previously established paralogy data, and, to compare vertebrates and Drosophila,
      orthology data.

PMID- 12519949
TI  - ArrayExpress--a public repository for microarray gene expression data at the EBI.
AB  - ArrayExpress is a new public database of microarray gene expression data at the
      EBI, which is a generic gene expression database designed to hold data from all
      microarray platforms. ArrayExpress uses the annotation standard Minimum
      Information About a Microarray Experiment (MIAME) and the associated XML data
      exchange format Microarray Gene Expression Markup Language (MAGE-ML) and it is
      designed to store well annotated data in a structured way. The ArrayExpress
      infrastructure consists of the database itself, data submissions in MAGE-ML
      format or via an online submission tool MIAMExpress, online database query
      interface, and the Expression Profiler online analysis tool. ArrayExpress accepts
      three types of submission, arrays, experiments and protocols, each of these is
      assigned an accession number. Help on data submission and annotation is provided
      by the curation team. The database can be queried on parameters such as author,
      laboratory, organism, experiment or array types. With an increasing number of
      organisations adopting MAGE-ML standard, the volume of submissions to
      ArrayExpress is increasing rapidly. The database can be accessed at
      http://www.ebi.ac.uk/arrayexpress.

PMID- 12519951
TI  - An improved version of the DNA Methylation database (MethDB).
AB  - Cytosine methylation is a characteristic property of prokaryotic and eukaryotic
      genomes. In the latter, it is indispensable for a healthy development of the
      organism and uncontrolled changes in the distribution of 5-methylcytosine (5mC)
      have been linked to severe disorders, in particular cancer. The growing
      scientific interest in DNA methylation has led to a considerable amount of data
      about this epigenetic phenomenon. In order to make these data readily available,
      we have established a dedicated database. The DNA Methylation database (MethDB)
      is currently the only public database for DNA methylation
      (http://www.methdb.net). This constantly growing database has become a key
      resource in the field of DNA methylation research. The database contains
      currently methylation patterns, profiles and total methylation content data for
      46 species, 160 tissues and 72 phenotypes coming from a total of 6667 experiments
      (as of September 4, 2002). About 14% of the data have not been published
      elsewhere. These data can be conveniently searched and represented in different
      ways. Recently, we have included an on-line submission tool that permits the
      scientific public to directly enter new data into MethDB.

PMID- 12519950
TI  - MEPD: a Medaka gene expression pattern database.
AB  - The Medaka Expression Pattern Database (MEPD) stores and integrates information
      of gene expression during embryonic development of the small freshwater fish
      Medaka (Oryzias latipes). Expression patterns of genes identified by ESTs are
      documented by images and by descriptions through parameters such as staining
      intensity, category and comments and through a comprehensive, hierarchically
      organized dictionary of anatomical terms. Sequences of the ESTs are available and
      searchable through BLAST. ESTs in the database are clustered upon entry and have
      been blasted against public data-bases. The BLAST results are updated regularly,
      stored within the database and searchable. The MEPD is a project within the
      Medaka Genome Initiative (MGI) and entries will be interconnected to integrated
      genomic map databases. MEPD is accessible through the WWW at
      http://medaka.dsp.jst.go.jp/MEPD.

PMID- 12519952
TI  - MTID: a database of Sleeping Beauty transposon insertions in mice.
AB  - The Sleeping Beauty (SB) transposon system provides the first random insertional
      mutagen available for germline genetic screens in mice. In preparation for a
      large scale project to create, map and manage up to 5000 SB insertions, we have
      developed the Mouse Transposon Insertion Database (MTID;
      http://mouse.ccgb.umn.edu/transposon/). Each insertion's genomic position, as
      well as the distance between the insertion and the nearest annotated gene, are
      determined by a sequence analysis pipeline. Users can search the database using a
      specified nucleotide or genetic map position to identify the nearest insertion.
      Mouse reports describe insertions carried, strain, genotype and dates of birth
      and death. Insertion reports describes chromosome, nucleotide and genetic map
      positions, as well as nearest gene data from Ensembl, NCBI and Celera. The
      flanking sequence used to map the insertion is also provided. Researchers will be
      able to identify insertions of interest and request mice or frozen sperm that
      carry the insertion.

PMID- 12519953
TI  - NetAffx: Affymetrix probesets and annotations.
AB  - NetAffx (http://www.affymetrix.com) details and annotates probesets on Affymetrix
      GeneChip microarrays. These annotations include (i) static information specific
      to the probeset composition; (ii) sequence annotations extracted from public
      databases; and (iii) protein sequence-level annotations derived from public
      domain programs, as well as libraries of hidden Markov models (HMMs) developed at
      Affymetrix. For each probeset, NetAffx lists the probe sequences, and the
      consensus sequence interrogated by the probes; for the larger chip sets,
      interactive maps display this sequence data in genomic context. Sequence
      annotations include Gene Ontology (GO) terms and depiction of GO graph
      relationships; predicted protein domains and motifs; orthologous sequences; links
      to relevant pathways; and links to public databases including UniGene, LocusLink,
      SWISS-PROT and OMIM.

PMID- 12519954
TI  - RECODE 2003.
AB  - The RECODE database is a compilation of translational recoding events (programmed
      ribosomal frameshifting, codon redefinition and translational bypass). The
      database provides information about the genes utilizing these events for their
      expression, recoding sites, stimulatory sequences and other relevant information.
      The Database is freely available at http://recode.genetics.utah.edu/.

PMID- 12519955
TI  - The Arabidopsis SeedGenes Project.
AB  - The SeedGenes database (http://www.seedgenes.org) presents molecular and
      phenotypic information on essential, non-redundant genes of Arabidopsis that give
      a seed phenotype when disrupted by mutation. Experimental details are synthesized
      for efficient use by the community and organized into two major sections in the
      database, one dealing with genes and the other with mutant alleles. The database
      can be queried for detailed information on a single gene to create a SeedGenes
      Profile. Queries can also generate lists of genes or mutants that fit specified
      criteria. The long-term goal is to establish a complete collection of Arabidopsis
      genes that give a knockout phenotype. This information is needed to focus
      attention on genes with important cellular functions in a model plant and to
      assess from a genetic perspective the extent of functional redundancy in the
      Arabidopsis genome.

PMID- 12519956
TI  - The Stanford Microarray Database: data access and quality assessment tools.
AB  - The Stanford Microarray Database (SMD; http://genome
      www.stanford.edu/microarray/) serves as a microarray research database for
      Stanford investigators and their collaborators. In addition, SMD functions as a
      resource for the entire scientific community, by making freely available all of
      its source code and providing full public access to data published by SMD users,
      along with many tools to explore and analyze those data. SMD currently provides
      public access to data from 3500 microarrays, including data from 85 publications,
      and this total is increasing rapidly. In this article, we describe some of SMD's
      newer tools for accessing public data, assessing data quality and for data
      analysis.

PMID- 12519957
TI  - TRANSPATH: an integrated database on signal transduction and a tool for array
      analysis.
AB  - TRANSPATH is a database system about gene regulatory networks that combines
      encyclopedic information on signal transduction with tools for visualization and
      analysis. The integration with TRANSFAC, a database about transcription factors
      and their DNA binding sites, provides the possibility to obtain complete
      signaling pathways from ligand to target genes and their products, which may
      themselves be involved in regulatory action. As of July 2002, the TRANSPATH
      Professional release 3.2 contains about 9800 molecules, >1800 genes and >11 400
      reactions collected from approximately 5000 references. With the ArrayAnalyzer,
      an integrated tool has been developed for evaluation of microarray data. It uses
      the TRANSPATH data set to identify key regulators in pathways connected with up-
      or down-regulated genes of the respective array. The key molecules and their
      surrounding networks can be viewed with the PathwayBuilder, a tool that offers
      four different modes of visualization. More information on TRANSPATH is available
      at http://www.biobase.de/pages/products/databases.html.

PMID- 12519958
TI  - ASAP: the Alternative Splicing Annotation Project.
AB  - Recently, genomics analyses have demonstrated that alternative splicing is
      widespread in mammalian genomes (30-60% of genes reported to have multiple
      isoforms), and may be one of their most important mechanisms of functional
      regulation. However, by comparison with other genomics data such as genome
      annotation, SNPs, or gene expression, there exists relatively little database
      infrastructure for the study of alternative splicing. We have constructed an
      online database ASAP (the Alternative Splicing Annotation Project) for biologists
      to access and mine the enormous wealth of alternative splicing information coming
      from genomics and proteomics. ASAP is based on genome-wide analyses of
      alternative splicing in human (30 793 alternative splice relationships found)
      from detailed alignment of expressed sequences onto the genomic sequence. ASAP
      provides precise gene exon-intron structure, alternative splicing, tissue
      specificity of alternative splice forms, and protein isoform sequences resulting
      from alternative splicing. Moreover, it can help biologists design probe
      sequences for distinguishing specific mRNA isoforms. ASAP is intended to be a
      community resource for collaborative annotation of alternative splice forms,
      their regulation, and biological functions. The URL for ASAP is
      http://www.bioinformatics.ucla.edu/ASAP.

PMID- 12519959
TI  - MICdb: database of prokaryotic microsatellites.
AB  - The MICdb (Microsatellites Database) (http://www.cdfd.org.in/micas) is a
      comprehensive relational database of non-redundant microsatellites extracted from
      fully sequenced prokaryotic genomes. The current version (1.0) of the database
      has been compiled from 83 genomes belonging to different phylogenetic groups.
      This database has been linked to MICAS, the web-based Microstatellite Analysis
      Server. MICAS provides a user-friendly front-end to systematically extract data
      on microsatellite tracts from genomes. The database contains the following
      information pertaining to the microsatellites: the regions (coding/non-coding, if
      coding, their GenBank annotations) containing microsatellite tracts; the
      frequencies of their occurrences, the size and the number of repeating motifs;
      and the sequences of the tracts. MICAS also provides an interface to Autoprimer,
      a primer design program to automatically design primers for selected
      microsatellite loci.

PMID- 12519960
TI  - PACRAT: a database and analysis system for archaeal and bacterial intergenic
      sequence features.
AB  - Analysis of intergenic sequences for purposes such as the investigation of
      transcriptional signals or the identification of small RNA genes is frequently
      complicated by traditional biological database structures. Genome data is
      commonly treated as chromosome-length sequence records, detailed by gene calls
      demarcating subsequences of the chromosomes. Given this model, the determination
      of non-called subsequences between any gene and its nearest neighbors requires an
      exhaustive search of all gene calls associated with the chromosome. Further
      compounding the issue, the location of intergenic regions for many called genes
      cannot be resolved unambiguously due to uncertainties in gene boundaries, as well
      as the presence of other conflicting gene calls. To address these difficulties we
      have constructed the PACRAT (http://www.biosci.ohio-state.edu/~pacrat/) database
      system. PACRAT preprocesses GenBank genome submissions, evaluates for every gene
      the character of its relationship to those genes nearest to it, and produces a
      relationally linked model of the gene ordering for the genome. Using this
      information, the interface allows the researcher to query gene data as well as
      intergenic sequence data based on a number of criteria. These include the ability
      to filter searches based on the status of start and stop positions, or
      upstream/downstream sequences as conflicting with called genes and automated
      extension of upstream or downstream searches to find probable operon promoters or
      terminators. The database is also indexed by KEGG classification, allowing, for
      example, functionally-related groups of high-quality promoter-containing regions
      to be easily retrieved as a group.

PMID- 12519961
TI  - PlantProm: a database of plant promoter sequences.
AB  - PlantProm DB, a plant promoter database, is an annotated, non-redundant
      collection of proximal promoter sequences for RNA polymerase II with
      experimentally determined transcription start site(s), TSS, from various plant
      species. The first release (2002.01) of PlantProm DB contains 305 entries
      including 71, 220 and 14 promoters from monocot, dicot and other plants,
      respectively. It provides DNA sequence of the promoter regions (-200 : +51) with
      TSS on the fixed position +201, taxonomic/promoter type classification of
      promoters and Nucleotide Frequency Matrices (NFM) for promoter elements: TATA
      box, CCAAT-box and TSS-motif (Inr). Analysis of TSS-motifs revealed that their
      composition is different in dicots and monocots, as well as for TATA and TATA
      less promoters. The database serves as learning set in developing plant promoter
      prediction programs. One such program (TSSP) based on discriminant analysis has
      been created by Softberry Inc. and the application of a support ftp: vector
      machine approach for promoter identification is under development. PlantProm DB
      is available at http://mendel.cs.rhul.ac.uk/ and http://www.softberry.com/.

PMID- 12519962
TI  - rSNP_Guide, a database system for analysis of transcription factor binding to DNA
      with variations: application to genome annotation.
AB  - The analysis of gene regulatory networks has become one of the most challenging
      problems of the postgenomic era. Earlier we developed rSNP_Guide
      (http://util.bionet.nsc.ru/databases/rsnp.html), a computer system and database
      devoted to prediction of transcription factor (TF) binding sites (TF sites),
      which can be responsible for disease phenotypes. The prediction results were
      confirmed by 70 known relationships between TF sites and diseases, as well as by
      site-directed mutagenesis data. The rSNP_Guide is being investigated as a tool
      for TF site annotation. Previously analyzed and characterized cases of altered TF
      sites were used to annotate potential sites of the same type and at the same
      location in homologous genes. Based on 20 TF sites with known alterations in TF
      binding to DNA, we localized 245 potential TF sites in homologous genes. For
      these potential TF sites, rSNP_Guide estimates TF-DNA interaction according to
      three categories: 'present', 'weak', and 'absent'. The significance of each
      assignment is statistically measured.

PMID- 12519963
TI  - RTPrimerDB: the real-time PCR primer and probe database.
AB  - The real-time polymerase chain reaction (PCR) methodology has become increasingly
      popular for nucleic acids detection and/or quantification. As primer/probe design
      and experimental evaluation is time-consuming, we developed a public database
      application for the storage and retrieval of validated real-time PCR primer and
      probe sequence records. The integrity and accuracy of the data are maintained by
      linking to and querying other reference databases. RTPrimerDB provides free
      public access through the Web to perform queries and submit user based
      information. Primer/probe records can be searched for by official gene symbol,
      nucleotide sequence, type of application, detection chemistry, LocusLink or
      Single Nucleotide Polymorphism (SNP) identifier, and submitter's name. Each
      record is directly linked to LocusLink, dbSNP and/or PubMed to retrieve
      additional information on the gene/SNP for which the primers/probes are designed.
      Currently, the database contains primer/probe records for human, mouse, rat,
      fruit fly and zebrafish, and all current detection chemistries such as
      intercalating dyes (SYBR Green I), hydrolysis probes (Taqman), adjacent
      hybridizations probes and molecular beacons. Real-time PCR primer/probe records
      are available at http://www.realtimeprimerdatabase.ht.st.

PMID- 12519964
TI  - The SNP Consortium website: past, present and future.
AB  - The SNP Consortium website (http://snp.cshl.org) has undergone many changes since
      its initial conception three years ago. The database back end has been changed
      from the venerable ACeDB to the more scalable MySQL engine. Users can access the
      data via gene or single nucleotide polymorphism (SNP) keyword searches and browse
      or dump SNP data to textfiles. A graphical genome browsing interface shows SNPs
      mapped onto the genome assembly in the context of externally available gene
      predictions and other features. SNP allele frequency and genotype data are
      available via FTP-download and on individual SNP report web pages. SNP linkage
      maps are available for download and for browsing in a comparative map viewer. All
      software components of the data coordinating center (DCC) website
      (http://snp.cshl.org) are open source.

PMID- 12519965
TI  - Sputnik: a database platform for comparative plant genomics.
AB  - Two million plant ESTs, from 20 different plant species, and totalling more than
      one 1000 Mbp of DNA sequence, represents a formidable transcriptomic resource.
      Sputnik uses the potential of this sequence resource to fill some of the
      information gap in the un-sequenced plant genomes and to serve as the foundation
      for in silicio comparative plant genomics. The complexity of the individual EST
      collections has been reduced using optimised EST clustering techniques.
      Annotation of cluster sequences is performed by exploiting and transferring
      information from the comprehensive knowledgebase already produced for the
      completed model plant genome (Arabidopsis thaliana) and by performing additional
      state of-the-art sequence analyses relevant to today's plant biologist.
      Functional predictions, comparative analyses and associative annotations for 500
      000 plant EST derived peptides make Sputnik (http://mips.gsf.de/proj/sputnik/) a
      valid platform for contemporary plant genomics.

PMID- 12519966
TI  - WormBase: a cross-species database for comparative genomics.
AB  - WormBase (http://www.wormbase.org/) is a web-accessible central data repository
      for information about Caenorhabditis elegans and related nematodes. The past two
      years have seen a significant expansion in the biological scope of WormBase,
      including the integration of large-scale, genome-wide data sets, the inclusion of
      genome sequence and gene predictions from related species and active literature
      curation. This expansion of data has also driven the development and refinement
      of user interfaces and operability, including a new Genome Browser, new searches
      and facilities for data access and the inclusion of extensive documentation.
      These advances have expanded WormBase beyond the obvious target audience of C.
      elegans researchers, to include researchers wishing to explore problems in
      functional and comparative genomics within the context of a powerful genetic
      system.

PMID- 12519967
TI  - The GENETPIG database: a tool for comparative mapping in pig (Sus scrofa).
AB  - The GENETPIG database has been established for storing and disseminating the
      results of the European project: 'GENETPIG: identification of genes controlling
      economic traits in pig'. The partners of this project have mapped about 630
      porcine and human ESTs onto the pig genome. The database collects the mapping
      results and links them to other sources of mapping data; this includes pig maps
      as well as available comparative mapping information. Functional annotation of
      the mapped ESTs is also given when a significant similarity to cognate genes was
      established. The database is accessible for consultation via the Internet at
      http://www.infobiogen.fr/services/Genetpig/.

PMID- 12519968
TI  - Human Gene-Centric Databases at the Weizmann Institute of Science: GeneCards,
      UDB, CroW 21 and HORDE.
AB  - Recent enhancements and current research in the GeneCards (GC)
      (http://bioinfo.weizmann.ac.il/cards/) project are described, including the
      addition of gene expression profiles and integrated gene locations. Also
      highlighted are the contributions of specialized associated human gene-centric
      databases developed at the Weizmann Institute. These include the Unified Database
      (UDB) (http://bioinfo.weizmann.ac.il/udb) for human genome mapping, the human
      Chromosome 21 database at the Weizmann Insti-tute (CroW 21)
      (http://bioinfo.weizmann.ac.il/crow21), and the Human Olfactory Receptor Data
      Explora-torium (HORDE) (http://bioinfo.weizmann.ac.il/HORDE). The synergistic
      relationships amongst these efforts have positively impacted the quality,
      quantity and usefulness of the GeneCards gene compendium.

PMID- 12519969
TI  - ASAP, a systematic annotation package for community analysis of genomes.
AB  - ASAP (a systematic annotation package for community analysis of genomes) is a
      relational database and web interface developed to store, update and distribute
      genome sequence data and functional characterization
      (https://asap.ahabs.wisc.edu/annotation/php/ASAP1.htm). ASAP facilitates ongoing
      community annotation of genomes and tracking of information as genome projects
      move from preliminary data collection through post-sequencing functional
      analysis. The ASAP database includes multiple genome sequences at various stages
      of analysis, corresponding experimental data and access to collections of related
      genome resources. ASAP supports three levels of users: public viewers, annotators
      and curators. Public viewers can currently browse updated annotation information
      for Escherichia coli K-12 strain MG1655, genome-wide transcript profiles from
      more than 50 microarray experiments and an extensive collection of mutant strains
      and associated phenotypic data. Annotators worldwide are currently using ASAP to
      participate in a community annotation project for the Erwinia chrysanthemi strain
      3937 genome. Curation of the E. chrysanthemi genome annotation as well as those
      of additional published enterobacterial genomes is underway and will be publicly
      accessible in the near future.

PMID- 12519970
TI  - BSD: the Biodegradative Strain Database.
AB  - The Biodegradative Strain Database (BSD) is a freely-accessible, web-based
      database providing detailed information on degradative bacteria and the hazardous
      substances that they degrade, including corresponding literature citations,
      relevant patents and links to additional web-based biological and chemical data.
      The BSD (http://bsd.cme.msu.edu) is being developed within the phylogenetic
      framework of the Ribosomal Database Project II (RDPII:
      http://rdp.cme.msu.edu/html) to provide a biological complement to the chemical
      and degradative pathway data of the University of Minnesota
      Biocatalysis/Biodegradation Database (UM-BBD: http://umbbd.ahc.umn.edu). Data is
      accessible through a series of strain, chemical and reference lists or by keyword
      search. The web site also includes on-line data submission and user survey forms
      to solicit user contributions and suggestions. The current release contains
      information on over 250 degradative bacterial strains and 150 hazardous
      substances. The transformation of xenobiotics and other environmentally toxic
      compounds by microorganisms is central to strategies for biocatalysis and the
      bioremediation of contaminated environments. However, practical, comprehensive,
      strain-level information on biocatalytic/biodegradative microbes is not readily
      available and is often difficult to compile. Similarly, for any given
      environmental contaminant, there is no single resource that can provide
      comparative information on the array of identified microbes capable of degrading
      the chemical. A web site that consolidates and cross-references strain, chemical
      and reference data related to biocatalysis, biotransformation, biodegradation and
      bioremediation would be an invaluable tool for academic and industrial
      researchers and environmental engineers.

PMID- 12519971
TI  - CATMA: a complete Arabidopsis GST database.
AB  - The Complete Arabidopsis Transcriptome Micro Array (CATMA) database contains gene
      sequence tag (GST) and gene model sequences for over 70% of the predicted genes
      in the Arabidopsis thaliana genome as well as primer sequences for GST
      amplification and a wide range of supplementary information. All CATMA GST
      sequences are specific to the gene for which they were designed, and all gene
      models were predicted from a complete reannotation of the genome using uniform
      parameters. The database is searchable by sequence name, sequence homology or
      direct SQL query, and is available through the CATMA website at
      http://www.catma.org/.

PMID- 12519972
TI  - CnidBase: The Cnidarian Evolutionary Genomics Database.
AB  - CnidBase, the Cnidarian Evolutionary Genomics Database, is a tool for
      investigating the evolutionary, developmental and ecological factors that affect
      gene expression and gene function in cnidarians. In turn, CnidBase will help to
      illuminate the role of specific genes in shaping cnidarian biodiversity in the
      present day and in the distant past. CnidBase highlights evolutionary changes
      between species within the phylum Cnidaria and structures genomic and expression
      data to facilitate comparisons to non-cnidarian metazoans. CnidBase aims to
      further the progress that has already been made in the realm of cnidarian
      evolutionary genomics by creating a central community resource which will help
      drive future research and facilitate more accurate classification and comparison
      of new experimental data with existing data. CnidBase is available at
      http://cnidbase.bu.edu/.

PMID- 12519973
TI  - The ERGO genome analysis and discovery system.
AB  - The ERGO (http://ergo.integratedgenomics.com/ERGO/) genome analysis and discovery
      suite is an integration of biological data from genomics, biochemistry, high
      throughput expression profiling, genetics and peer-reviewed journals to achieve a
      comprehensive analysis of genes and genomes. Far beyond any conventional systems
      that facilitate functional assignments, ERGO combines pattern-based analysis with
      comparative genomics by visualizing genes within the context of regulation,
      expression profiling, phylogenetic clusters, fusion events, networked cellular
      pathways and chromosomal neighborhoods of other functionally related genes. The
      result of this multifaceted approach is to provide an extensively curated
      database of the largest available integration of genomes, with a vast collection
      of reconstructed cellular pathways spanning all domains of life. Although access
      to ERGO is provided only under subscription, it is already widely used by the
      academic community. The current version of the system integrates 500 genomes from
      all domains of life in various levels of completion, 403 of which are available
      for subscription.

PMID- 12519974
TI  - The FlyBase database of the Drosophila genome projects and community literature.
AB  - FlyBase (http://flybase.bio.indiana.edu/) provides an integrated view of the
      fundamental genomic and genetic data on the major genetic model Drosophila
      melanogaster and related species. FlyBase has primary responsibility for the
      continual reannotation of the D. melanogaster genome. The ultimate goal of the
      reannotation effort is to decorate the euchromatic sequence of the genome with as
      much biological information as is available from the community and from the major
      genome project centers. A complete revision of the annotations of the now
      finished euchromatic genomic sequence has been completed. There are many points
      of entry to the genome within FlyBase, most notably through maps, gene products
      and ontologies, structured phenotypic and gene expression data, and anatomy.

PMID- 12519975
TI  - GOBASE--a database of mitochondrial and chloroplast information.
AB  - GOBASE is a relational database containing integrated sequence, RNA secondary
      structure and biochemical and taxonomic information about organelles. GOBASE
      release 6 (summer 2002) contains over 130 000 mitochondrial sequences, an
      increase of 37% over the previous release, and more than 30 000 chloroplast
      sequences in a new auxiliary database. To handle this flood of new data, we have
      designed and implemented GOpop, a Java system for population and verification of
      the database. We have also implemented a more powerful and flexible user
      interface using the PHP programming language.
      http://megasun.bch.umontreal.ca/gobase/gobase.html.

PMID- 12519976
TI  - GenoPlante-Info (GPI): a collection of databases and bioinformatics resources for
      plant genomics.
AB  - Genoplante is a partnership program between public French institutes (INRA,
      CIRAD, IRD and CNRS) and private companies (Biogemma, Bayer CropScience and
      Bioplante) that aims at developing genome analysis programs for crop species
      (corn, wheat, rapeseed, sunflower and pea) and model plants (Arabidopsis and
      rice). The outputs of these programs form a wealth of information (genomic
      sequence, transcriptome, proteome, allelic variability, mapping and synteny, and
      mutation data) and tools (databases, interfaces, analysis software), that are
      being integrated and made public at the public bioinformatics resource centre of
      Genoplante: GenoPlante-Info (GPI). This continuous flood of data and tools is
      regularly updated and will grow continuously during the coming two years. Access
      to the GPI databases and tools is available at http://genoplante
      info.infobiogen.fr/.

PMID- 12519977
TI  - GrainGenes, the genome database for small-grain crops.
AB  - GrainGenes, http://www.graingenes.org, is the international database for the
      wheat, barley, rye and oat genomes. For these species it is the primary
      repository for information about genetic maps, mapping probes and primers, genes,
      alleles and QTLs. Documentation includes such data as primer sequences,
      polymorphism descriptions, genotype and trait scoring data, experimental
      protocols used, and photographs of marker polymorphisms, disease symptoms and
      mutant phenotypes. These data, curated with the help of many members of the
      research community, are integrated with sequence and bibliographic records
      selected from external databases and results of BLAST searches of the ESTs.
      Records are linked to corresponding records in other important databases, e.g.
      Gramene's EST homologies to rice BAC/PACs, TIGR's Gene Indices and GenBank. In
      addition to this information within the GrainGenes database itself, the
      GrainGenes homepage at http://wheat.pw.usda.gov provides many other community
      resources including publications (the annual newsletters for wheat, barley and
      oat, monographs and articles), individual datasets (mapping and QTL studies,
      polymorphism surveys, variety performance evaluations), specialized databases
      (Triticeae repeat sequences, EST unigene sets) and pages to facilitate
      coordination of cooperative research efforts in specific areas such as SNP
      development, EST-SSRs and taxonomy. The goal is to serve as a central point for
      obtaining and contributing information about the genetics and biology of these
      cereal crops.

PMID- 12519978
TI  - HGT-DB: a database of putative horizontally transferred genes in prokaryotic
      complete genomes.
AB  - The Horizontal Gene Transfer DataBase (HGT-DB) is a genomic database that
      includes statistical parameters such as G+C content, codon and amino-acid usage,
      as well as information about which genes deviate in these parameters for
      prokaryotic complete genomes. Under the hypothesis that genes from distantly
      related species have different nucleotide compositions, these deviated genes may
      have been acquired by horizontal gene transfer. The current version of the
      database contains 88 bacterial and archaeal complete genomes, including multiple
      chromosomes and strains. For each genome, the database provides statistical
      parameters for all the genes, as well as averages and standard deviations of G+C
      content, codon usage, relative synonymous codon usage and amino-acid content. It
      also provides information about correspondence analyses of the codon usage, plus
      lists of extraneous group of genes in terms of G+C content and lists of
      putatively acquired genes. With this information, researchers can explore the G+C
      content and codon usage of a gene when they find incongruities in sequence-based
      phylogenetic trees. A search engine that allows searches for gene names or
      keywords for a specific organism is also available. HGT-DB is freely accessible
      at http://www.fut.es/~debb/HGT.

PMID- 12519979
TI  - MOsDB: an integrated information resource for rice genomics.
AB  - The MIPS Rice (Oryza sativa) database (MOsDB; http://mips.gsf.de/proj/rice)
      provides a comprehensive data collection dedicated to the genome information of
      rice. Rice (O. sativa L.) is one of the most important food crops for over half
      the world's population and serves as a major model system in cereal genome
      research. MOsDB integrates data from two publicly available rice genomic
      sequences, O. sativa L. ssp. indica and O. sativa L. ssp. japonica. Besides
      regularly updated rice genome sequence information, MOsDB provides an integrated
      resource for associated analysis data, e.g. internal and external annotation
      information as well as a complex characterization of all annotated rice genes.
      The MOsDB web interface supports various search options and allows browsing the
      database content. MOsDB is continuously expanding to include an increasing range
      of data type and the growing amount of information on the rice genome.

PMID- 12519980
TI  - MGD: the Mouse Genome Database.
AB  - The Mouse Genome Database (MGD) (http://www.informatics.jax.org) one component of
      a community database resource for the laboratory mouse, a key model organism for
      interpreting the human genome and for understanding human biology. MGD strives to
      provide an extensively integrated information resource with experimental details
      annotated from both literature and on-line genomic data sources. MGD curates and
      presents the consensus representation of genotype (sequence) to phenotype
      information including highly detailed information about genes and gene products.
      Primary foci of integration are through representations of relationships between
      genes, sequences and phenotypes. MGD collaborates with other bioinformatics
      groups to curate a definitive set of information about the laboratory mouse.
      Recent developments include a general implementation of database structures for
      controlled vocabularies and the integration of a phenotype classification system.

PMID- 12519981
TI  - MtDB: a database for personalized data mining of the model legume Medicago
      truncatula transcriptome.
AB  - In order to identify the genes and gene functions that underlie key aspects of
      legume biology, researchers have selected the cool season legume Medicago
      truncatula (Mt) as a model system for legume research. A set of >170 000 Mt ESTs
      has been assembled based on in-depth sampling from various developmental stages
      and pathogen-challenged tissues. MtDB is a relational database that integrates Mt
      transcriptome data and provides a wide range of user-defined data mining options.
      The database is interrogated through a series of interfaces with 58 options
      grouped into two filters. In addition, the user can select and compare unigene
      sets generated by different assemblers: Phrap, Cap3 and Cap4. Sequence
      identifiers from all public Mt sites (e.g. IDs from GenBank, CCGB, TIGR, NCGR,
      INRA) are fully cross-referenced to facilitate comparisons between different
      sites, and hypertext links to the appropriate database records are provided for
      all queries' results. MtDB's goal is to provide researchers with the means to
      quickly and independently identify sequences that match specific research
      interests based on user-defined criteria. The underlying database and query
      software have been designed for ease of updates and portability to other model
      organisms. Public access to the database is at http://www.medicago.org/MtDB.

PMID- 12519982
TI  - OGRe: a relational database for comparative analysis of mitochondrial genomes.
AB  - Organellar Genome Retrieval (OGRe) is a relational database of complete
      mitochondrial genome sequences for over 250 Metazoan species. OGRe provides a
      resource for the comparative analysis of mitochondrial genomes at several levels.
      At the sequence level, OGRe allows the retrieval of any selected set of
      mitochondrial genes from any selected set of species. Species are classified
      using a taxonomic system that allows easy selection of related groups of species.
      Sequence alignments are also available for some species. At the level of
      individual nucleotides, the system contains information on base frequencies and
      codon usage frequencies that can be compared between organisms. At the level of
      whole genomes, OGRe provides several ways of visualizing information on gene
      order. Diagrams illustrating the genome arrangement can be generated for any
      selected set of species automatically from the information in the database.
      Searches can be done based on gene arrangement to find sets of species that have
      the same order as one another. Diagrams for pairwise comparison of species can be
      produced that show the positions of break-points in the gene order and use colour
      to highlight the sections of the genome that have moved. OGRe is available from
      http://www.bioinf.man.ac.uk/ogre.

PMID- 12519984
TI  - PlasmoDB: the Plasmodium genome resource. A database integrating experimental and
      computational data.
AB  - PlasmoDB (http://PlasmoDB.org) is the official database of the Plasmodium
      falciparum genome sequencing consortium. This resource incorporates the recently
      completed P. falciparum genome sequence and annotation, as well as draft sequence
      and annotation emerging from other Plasmodium sequencing projects. PlasmoDB
      currently houses information from five parasite species and provides tools for
      intra- and inter-species comparisons. Sequence information is integrated with
      other genomic-scale data emerging from the Plasmodium research community,
      including gene expression analysis from EST, SAGE and microarray projects and
      proteomics studies. The relational schema used to build PlasmoDB, GUS (Genomics
      Unified Schema) employs a highly structured format to accommodate the diverse
      data types generated by sequence and expression projects. A variety of tools
      allow researchers to formulate complex, biologically-based, queries of the
      database. A stand-alone version of the database is also available on CD-ROM (P.
      falciparum GenePlot), facilitating access to the data in situations where
      internet access is difficult (e.g. by malaria researchers working in the field).
      The goal of PlasmoDB is to facilitate utilization of the vast quantities of
      genomic-scale data produced by the global malaria research community. The
      software used to develop PlasmoDB has been used to create a second Apicomplexan
      parasite genome database, ToxoDB (http://ToxoDB.org).

PMID- 12519983
TI  - The PEDANT genome database.
AB  - The PEDANT genome database (http://pedant.gsf.de) provides exhaustive automatic
      analysis of genomic sequences by a large variety of established bioinformatics
      tools through a comprehensive Web-based user interface. One hundred and seventy
      seven completely sequenced and unfinished genomes have been processed so far,
      including large eukaryotic genomes (mouse, human) published recently. In this
      contribution, we describe the current status of the PEDANT database and novel
      analytical features added to the PEDANT server in 2002. Those include: (i)
      integration with the BioRS data retrieval system which allows fast text queries,
      (ii) pre-computed sequence clusters in each complete genome, (iii) a
      comprehensive set of tools for genome comparison, including genome comparison
      tables and protein function prediction based on genomic context, and (iv)
      computation and visualization of protein-protein interaction (PPI) networks based
      on experimental data. The availability of functional and structural predictions
      for 650 000 genomic proteins in well organized form makes PEDANT a useful
      resource for both functional and structural genomics.

PMID- 12519985
TI  - Saccharomyces Genome Database (SGD) provides biochemical and structural
      information for budding yeast proteins.
AB  - The Saccharomyces Genome Database (SGD: http://genome
      www.stanford.edu/Saccharomyces/) has recently developed new resources to provide
      more complete information about proteins from the budding yeast Saccharomyces
      cerevisiae. The PDB Homologs page provides structural information from the
      Protein Data Bank (PDB) about yeast proteins and/or their homologs. SGD has also
      created a resource that utilizes the eMOTIF database for motif information about
      a given protein. A third new resource is the Protein Information page, which
      contains protein physical and chemical properties, such as molecular weight and
      hydropathicity scores, predicted from the translated ORF sequence.

PMID- 12519986
TI  - SOURCE: a unified genomic resource of functional annotations, ontologies, and
      gene expression data.
AB  - The explosion in the number of functional genomic datasets generated with tools
      such as DNA microarrays has created a critical need for resources that facilitate
      the interpretation of large-scale biological data. SOURCE is a web-based database
      that brings together information from a broad range of resources, and provides it
      in manner particularly useful for genome-scale analyses. SOURCE's GeneReports
      include aliases, chromosomal location, functional descriptions, GeneOntology
      annotations, gene expression data, and links to external databases. We curate
      published microarray gene expression datasets and allow users to rapidly identify
      sets of co-regulated genes across a variety of tissues and a large number of
      conditions using a simple and intuitive interface. SOURCE provides content both
      in gene and cDNA clone-centric pages, and thus simplifies analysis of datasets
      generated using cDNA microarrays. SOURCE is continuously updated and contains the
      most recent and accurate information available for human, mouse, and rat genes.
      By allowing dynamic linking to individual gene or clone reports, SOURCE
      facilitates browsing of large genomic datasets. Finally, SOURCEs batch interface
      allows rapid extraction of data for thousands of genes or clones at once and thus
      facilitates statistical analyses such as assessing the enrichment of functional
      attributes within clusters of genes. SOURCE is available at
      http://source.stanford.edu.

PMID- 12519987
TI  - The Arabidopsis Information Resource (TAIR): a model organism database providing
      a centralized, curated gateway to Arabidopsis biology, research materials and
      community.
AB  - Arabidopsis thaliana is the most widely-studied plant today. The concerted
      efforts of over 11 000 researchers and 4000 organizations around the world are
      generating a rich diversity and quantity of information and materials. This
      information is made available through a comprehensive on-line resource called the
      Arabidopsis Information Resource (TAIR) (http://arabidopsis.org), which is
      accessible via commonly used web browsers and can be searched and downloaded in a
      number of ways. In the last two years, efforts have been focused on increasing
      data content and diversity, functionally annotating genes and gene products with
      controlled vocabularies, and improving data retrieval, analysis and visualization
      tools. New information include sequence polymorphisms including alleles,
      germplasms and phenotypes, Gene Ontology annotations, gene families, protein
      information, metabolic pathways, gene expression data from microarray experiments
      and seed and DNA stocks. New data visualization and analysis tools include
      SeqViewer, which interactively displays the genome from the whole chromosome down
      to 10 kb of nucleotide sequence and AraCyc, a metabolic pathway database and map
      tool that allows overlaying expression data onto the pathway diagrams. Finally,
      we have recently incorporated seed and DNA stock information from the Arabidopsis
      Biological Resource Center (ABRC) and implemented a shopping-cart style on-line
      ordering system.

PMID- 12519989
TI  - ToxoDB: accessing the Toxoplasma gondii genome.
AB  - ToxoDB (http://ToxoDB.org) provides a genome resource for the protozoan parasite
      Toxoplasma gondii. Several sequencing projects devoted to T. gondii have been
      completed or are in progress: an EST project
      (http://genome.wustl.edu/est/index.php?toxoplasma=1), a BAC clone end-sequencing
      project (http://www.sanger.ac.uk/Projects/T_gondii/) and an 8X random shotgun
      genomic sequencing project (http://www.tigr.org/tdb/e2k1/tga1/). ToxoDB was
      designed to provide a central point of access for all available T. gondii data,
      and a variety of data mining tools useful for the analysis of unfinished, un
      annotated draft sequence during the early phases of the genome project. In later
      stages, as more and different types of data become available (microarray,
      proteomic, SNP, QTL, etc.) the database will provide an integrated data analysis
      platform facilitating user-defined queries across the different data types.

PMID- 12519988
TI  - The TIGR rice genome annotation resource: annotating the rice genome and creating
      resources for plant biologists.
AB  - Rice is not only a major food staple for the world's population but it also is a
      model species for a major group of flowering plants, the monocotyledonous plants.
      Draft genomic sequence of two subspecies of rice, Oryza sativa spp. japonica and
      indica ssp. are publicly available. To provide the community with a resource to
      data-mine the rice genome, we have constructed an annotation resource for rice
      (http://www.tigr.org/tdb/e2k1/osa1/). In this resource, we have annotated the
      rice genome for gene content, identified motifs/domains within the predicted
      genes, constructed a rice repeat database, identified related sequences in other
      plant species, and identified syntenic sequences between rice and maize. All of
      the data is available through web-based interfaces, FTP downloads, and a
      Distributed Annotation System.

PMID- 12519990
TI  - WorfDB: the Caenorhabditis elegans ORFeome Database.
AB  - WorfDB (Worm ORFeome DataBase; http://worfdb.dfci.harvard.edu) was created to
      integrate and disseminate the data from the cloning of complete set of
      approximately 19 000 predicted protein-encoding Open Reading Frames (ORFs) of
      Caenorhabditis elegans (also referred to as the 'worm ORFeome'). WorfDB serves as
      a central data repository enabling the scientific community to search for
      availability and quality of cloned ORFs. So far, ORF sequence tags (OSTs)
      obtained for all individual clones have allowed exon structure corrections for
      approximately 3400 ORFs originally predicted by the C. elegans sequencing
      consortium. In addition, we now have OSTs for approximately 4300 predicted genes
      for which no ESTs were available. The database contains this OST information
      along with data pertinent to the cloning process. WorfDB could serve as a model
      database for other metazoan ORFeome cloning projects.

PMID- 12519991
TI  - The Zebrafish Information Network (ZFIN): the zebrafish model organism database.
AB  - The Zebrafish Information Network (ZFIN) is a web based community resource that
      serves as a centralized location for the curation and integration of zebrafish
      genetic, genomic and developmental data. ZFIN is publicly accessible at
      http://zfin.org. ZFIN provides an integrated representation of mutants, genes,
      genetic markers, mapping panels, publications and community contact data. Recent
      enhancements to ZFIN include: (i) an anatomical dictionary that provides a
      controlled vocabulary of anatomical terms, grouped by developmental stages, that
      may be used to annotate and query gene expression data; (ii) gene expression
      data; (iii) expanded support for genome sequence; (iv) gene annotation using the
      standardized vocabulary of Gene Ontology (GO) terms that can be used to elucidate
      relationships between gene products in zebrafish and other organisms; and (v)
      collaborations with other databases (NCBI, Sanger Institute and SWISS-PROT) to
      provide standardization and interconnections based on shared curation.

PMID- 12519992
TI  - ZmDB, an integrated database for maize genome research.
AB  - Zea mays DataBase (ZmDB) seeks to provide a comprehensive view of maize (corn)
      genetics by linking genomic sequence data with gene expression analysis and
      phenotypes of mutant plants. ZmDB originated in 1999 as the Web portal for a
      large project of maize gene discovery, sequencing and phenotypic analysis using a
      transposon tagging strategy and expressed sequence tag (EST) sequencing.
      Recently, ZmDB has broadened its scope to include all public maize ESTs, genome
      survey sequences (GSSs), and protein sequences. More than 170 000 ESTs are
      currently clustered into approximately 20 000 contigs and about an equal number
      of apparent singlets. These clusters are continuously updated and annotated with
      respect to potential encoded protein products. More than 100 000 GSSs are
      similarly assembled and annotated by spliced alignment with EST and protein
      sequences. The ZmDB interface provides quick access to analytical tools for
      further sequence analysis. Every sequence record is linked to several display
      options and similarity search tools, including services for multiple sequence
      alignment, protein domain determination and spliced alignment. Furthermore, ZmDB
      provides web-based ordering of materials generated in the project, including
      ESTs, ordered collections of genomic sequences tagged with the RescueMu
      transposon and microarrays of amplified ESTs. ZmDB can be accessed at
      http://zmdb.iastate.edu/.

PMID- 12519993
TI  - BIND: the Biomolecular Interaction Network Database.
AB  - The Biomolecular Interaction Network Database (BIND: http://bind.ca) archives
      biomolecular interaction, complex and pathway information. A web-based system is
      available to query, view and submit records. BIND continues to grow with the
      addition of individual submissions as well as interaction data from the PDB and a
      number of large-scale interaction and complex mapping experiments using yeast two
      hybrid, mass spectrometry, genetic interactions and phage display. We have
      developed a new graphical analysis tool that provides users with a view of the
      domain composition of proteins in interaction and complex records to help relate
      functional domains to protein interactions. An interaction network clustering
      tool has also been developed to help focus on regions of interest. Continued
      input from users has helped further mature the BIND data specification, which now
      includes the ability to store detailed information about genetic interactions.
      The BIND data specification is available as ASN.1 and XML DTD.

PMID- 12519994
TI  - InterDom: a database of putative interacting protein domains for validating
      predicted protein interactions and complexes.
AB  - Advances in proteomics technology have enabled new proteins to be discovered at
      an unprecedented speed, and high throughput experimental methods have been
      developed to detect protein interactions and complexes en masse. Such bottom-up,
      data-driven approach has resulted in data that may be uninformative or
      potentially errorful, requiring further validation and annotation. The InterDom
      database focuses on providing supporting evidence for the detected protein
      interactions based on putative protein domain interactions. Using an integrative
      approach, InterDom derives potential domain interactions by combining data from
      multiple sources, ranging from domain fusions, protein interactions and
      complexes, to scientific literature. The InterDom database is available at
      http://InterDom.lit.org.sg.

PMID- 12519995
TI  - KDBI: Kinetic Data of Bio-molecular Interactions database.
AB  - Understanding of cellular processes and underlying molecular events requires
      knowledge about different aspects of molecular interactions, networks of
      molecules and pathways in addition to the sequence, structure and function of
      individual molecules involved. Databases of interacting molecules, pathways and
      related chemical reaction equations have been developed. The kinetic data for
      these interactions, which is important for mechanistic investigation,
      quantitative study and simulation of cellular processes and events, is not
      provided in the existing databases. We introduce a new database of Kinetic Data
      of Bio-molecular Interactions (KDBI) aimed at providing experimentally determined
      kinetic data of protein-protein, protein-RNA, protein-DNA, protein-ligand, RNA
      ligand, DNA-ligand binding or reaction events described in the literature. KDBI
      contains information about binding or reaction event, participating molecules
      (name, synonyms, molecular formula, classification, SWISS-PROT AC or CAS number),
      binding or reaction equation, kinetic data and related references. The kinetic
      data is in terms of one or a combination of the following quantities as given in
      the literature of a particular event: association/dissociation or on/off rate
      constant, first/second/third/. order rate constant, equilibrium rate constant,
      catalytic rate constant, equilibrium association/dissociation constant,
      inhibition constant and binding affinity constant. Each entry can be retrieved
      through protein or nucleic acid or ligand name, SWISS-PROT AC number, ligand CAS
      number and full-text search of a binding or reaction event. KDBI currently
      contains 8273 entries of biomolecular binding or reaction events involving 1380
      proteins, 143 nucleic acids and 1395 small molecules. Hyperlinks are provided for
      accessing references in Medline and available 3D structures in PDB and NDB. This
      database can be accessed at http://xin.cz3.nus.edu.sg/group/kdbi/kdbi.asp.

PMID- 12519996
TI  - STRING: a database of predicted functional associations between proteins.
AB  - Functional links between proteins can often be inferred from genomic associations
      between the genes that encode them: groups of genes that are required for the
      same function tend to show similar species coverage, are often located in close
      proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion
      events. The database STRING is a precomputed global resource for the exploration
      and analysis of these associations. Since the three types of evidence differ
      conceptually, and the number of predicted interactions is very large, it is
      essential to be able to assess and compare the significance of individual
      predictions. Thus, STRING contains a unique scoring-framework based on benchmarks
      of the different types of associations against a common reference set, integrated
      in a single confidence score per prediction. The graphical representation of the
      network of inferred, weighted protein interactions provides a high-level view of
      functional linkage, facilitating the analysis of modularity in biological
      processes. STRING is updated continuously, and currently contains 261 033
      orthologs in 89 fully sequenced genomes. The database predicts functional
      interactions at an expected level of accuracy of at least 80% for more than half
      of the genes; it is online at http://www.bork.embl-heidelberg.de/STRING/.

PMID- 12519997
TI  - The University of Minnesota Biocatalysis/Biodegradation Database: post-genomic
      data mining.
AB  - The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD,
      http://umbbd.ahc.umn.edu/) provides curated information on microbial catabolism
      and related biotransformations, primarily for environmental pollutants.
      Currently, it contains information on over 130 metabolic pathways, 800 reactions,
      750 compounds and 500 enzymes. In the past two years, it has increased its breath
      to include more examples of microbial metabolism of metals and metalloids; and
      expanded the types of information it includes to contain microbial
      biotransformations of, and binding interactions with many chemical elements. It
      has also increased the ways in which this data can be accessed (mined). Structure
      based searching was added, for exact matches, similarity, or substructures.
      Analysis of UM-BBD reactions has lead to a prototype, guided, pathway prediction
      system. Guided prediction means that the user is shown all possible
      biotransformations at each step and guides the process to its conclusion. Mining
      the UM-BBD's data provides a unique view into how the microbial world recycles
      organic functional groups. UM-BBD users are encouraged to comment on all aspects
      of the database, including the information it contains and the tools by which it
      can be mined. The database and prediction system develop under the direction of
      the scientific community.

PMID- 12519998
TI  - PRODORIC: prokaryotic database of gene regulation.
AB  - The database PRODORIC aims to systematically organize information on prokaryotic
      gene expression, and to integrate this information into regulatory networks. The
      present version focuses on pathogenic bacteria such as Pseudomonas aeruginosa.
      PRODORIC links data on environmental stimuli with trans-acting transcription
      factors, cis-acting promoter elements and regulon definition. Interactive
      graphical representations of operon, gene and promoter structures including
      regulator-binding sites, transcriptional and translational start sites,
      supplemented with information on regulatory proteins are available at varying
      levels of detail. The data collection provided is based on exhaustive analyses of
      scientific literature and computational sequence prediction. Included within
      PRODORIC are tools to define and predict regulator binding sites. It is
      accessible at http://prodoric.tu-bs.de.

PMID- 12519999
TI  - ALFRED: the ALelle FREquency Database. Update.
AB  - Elaboration of ALFRED (http://alfred.med.yale.edu) is being continued in two
      directions. One of which is developing tools for efficiently annotating the
      entries and checking the integrity of the data already in the database while the
      other is to increase the quantity and accessibility of data. Information
      contained in ALFRED such as, polymorphic sites, number of populations and
      frequency tables (one sample typed for one site) has significantly increased.

PMID- 12520000
TI  - Atlas of Genetics and Cytogenetics in Oncology and Haematology, year 2003.
AB  - The 'Atlas of Genetics and Cytogenetics in Oncology and Haematology'
      (http://www.infobiogen.fr/services/chromcancer) contains concise and updated
      cards on genes involved in cancer, cytogenetics and clinical entities in
      oncology, and cancer-prone diseases, a portal towards genetics/cancer, and
      teaching materials in genetics. This database is made for and by researchers and
      clinicians, who are encouraged to contribute. The Atlas is part of the genome
      project and it participates in research on cancer epidemiology.

PMID- 12520001
TI  - Online Mendelian Inheritance in Animals (OMIA): a comparative knowledgebase of
      genetic disorders and other familial traits in non-laboratory animals.
AB  - Online Mendelian Inheritance in Animals (OMIA) provides up-to-date information on
      inherited disorders and other familial traits in non-laboratory animals. It is
      freely available online at http://www.angis.org.au/omia. With a strong emphasis
      on comparative biology, OMIA is modelled on, and reciprocally hyperlinked with,
      Online Mendelian Inheritance in Man (OMIM). It provides a comprehensive catalog
      of animal models of human inherited disorders, and also provides comprehensive
      access to information on potential human homologues of inherited disorders and
      traits in animals. Because its whole structure is based on comparative biology,
      it provides phenotypic information in a format that is complementary to all the
      relevant mapping and sequence databases now existing or being created across the
      animal kingdom.

PMID- 12520002
TI  - BayGenomics: a resource of insertional mutations in mouse embryonic stem cells.
AB  - The BayGenomics gene-trap resource (http://baygenomics.ucsf.edu) provides
      researchers with access to thousands of mouse embryonic stem (ES) cell lines
      harboring characterized insertional mutations in both known and novel genes. Each
      cell line contains an insertional mutation in a specific gene. The identity of
      the gene that has been interrupted can be determined from a DNA sequence tag.
      Approximately 75% of our cell lines contain insertional mutations in known mouse
      genes or genes that share strong sequence similarities with genes that have been
      identified in other organisms. These cell lines readily transmit the mutation to
      the germline of mice and many mutant lines of mice have already been generated
      from this resource. BayGenomics provides facile access to our entire database,
      including sequence tags for each mutant ES cell line, through the World Wide Web.
      Investigators can browse our resource, search for specific entries, download any
      portion of our database and BLAST sequences of interest against our entire set of
      cell line sequence tags. They can then obtain the mutant ES cell line for the
      purpose of generating knockout mice.

PMID- 12520003
TI  - INFEVERS: the Registry for FMF and hereditary inflammatory disorders mutations.
AB  - We have established the INFEVERS--INternet periodic FEVERS--website (which is
      freely accessible at http://fmf.igh.cnrs.fr/infevers/). Our objectives were to
      develop a specialist site to gather updated information on mutations responsible
      for hereditary inflammatory disorders: i.e. Familial Mediterranean Fever (FMF),
      TRAPS (TNF Receptor 1A Associated Syndrome), HIDS (HyperIgD Syndrome), MWS
      (Muckle-Wells Syndrome)/FCU (Familial Cold Urticaria)/CINCA (Chronic Infantile
      Neurological Cutaneous and Articular Syndrome). Contributors submit their novel
      mutations through a 3 step form. Depending on the disease concerned, a member of
      the editorial board is automatically solicited to overview and validate new
      submissions, via a special secured web interface. If accepted, the new mutation
      is available on the INFEVERS web site and the discoverer, who is informed by
      email, is credited by having his/her name and date of the discovery on the site.
      The INFEVERS gateway provides researchers and clinicians with a common access
      location for information on similar diseases, allowing a rapid overview of the
      corresponding genetic defects at a glance. Furthermore, it is interactive and
      extendable according to the latest genes discovered.

PMID- 12520004
TI  - The MetaFMF website: a high quality tool for meta-analysis of FMF.
AB  - We present here the MetaFMF database (freely accessible at
      http://fmf.igh.cnrs.fr/metaFMF/index_us.html) that attempts to gather and unify,
      in a common resource, data on phenotype-genotype correlation in familial
      Mediterranean fever (FMF). A single accession form, including a large number of
      quality controls, has been implemented such that data, collected worldwide, are
      included in an homogeneous manner. The inclusion criterion has the objective to
      avoid interpretational bias: patients will be included only if they bear at least
      two mutations. The clinical form has been set up by an International editorial
      board (12 FMF expert centres), which guarantees the validity of the data. Data
      are anonymous and submitted by a secure interface, in which the researcher is
      logged in with a specific ID and password. A pilot study on 211 patients has
      shown the feasibility and relevance of this project. We anticipate that the use
      of MetaFMF will enable reliable assessment of phenotype-genotype correlations in
      FMF, and define a set of severe versus mild mutations/genotypes. It should also
      highlight reasons for previous inconsistencies in such correlations.

PMID- 12520005
TI  - PGDB: a curated and integrated database of genes related to the prostate.
AB  - The Prostate Gene Database (PGDB: http://www.ucsf.edu/pgdb) is a curated and
      integrated database of genes or genomic loci related to the human prostate and
      prostatic diseases. Currently, PGDB covers genes involved in a number of
      molecular and genetic events of the prostate including gene amplification,
      mutation, gross deletion, methylation, polymorphism, linkage and over-expression,
      as published in the literature. Genes that are specifically expressed in
      prostate, as evidenced by analysis of data from expressed sequence tags (ESTs)
      and serial analysis of gene expression (SAGE), are also included. There are a
      total of 165 unique entries in the database. Users can either browse or query the
      PGDB through a web interface. For each gene, in addition to basic gene
      information and rich cross-references to other databases, inclusive and relevant
      literature references are provided to support the inclusion of the gene in the
      database. Detailed expression data calculated from the UniGene and SAGEmap
      databases are also presented.

PMID- 12520006
TI  - GPCRDB information system for G protein-coupled receptors.
AB  - The GPCRDB is a molecular class-specific information system that collects,
      combines, validates and disseminates heterogeneous data on G protein-coupled
      receptors (GPCRs). The database stores data on sequences, ligand binding
      constants and mutations. The system also provides computationally derived data
      such as sequence alignments, homology models, and a series of query and
      visualization tools. The GPCRDB is updated automatically once every 4-5 months
      and is freely accessible at http://www.gpcr.org/7tm/.

PMID- 12520007
TI  - Human immunodeficiency virus reverse transcriptase and protease sequence
      database.
AB  - The HIV reverse transcriptase and protease sequence database is an on-line
      relational database that catalogues evolutionary and drug-related sequence
      variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT)
      and protease enzymes, the molecular targets of antiretroviral therapy
      (http://hivdb.stanford.edu). The database contains a compilation of nearly all
      published HIV RT and protease sequences, including submissions to GenBank,
      sequences published in journal articles and sequences of HIV isolates from
      persons participating in clinical trials. Sequences are linked to data about the
      source of the sequence, the antiretroviral drug treatment history of the person
      from whom the sequence was obtained and the results of in vitro drug
      susceptibility testing. Sequence data on two new molecular targets of HIV drug
      therapy--gp41 (cell fusion) and integrase--will be added to the database in 2003.

PMID- 12520008
TI  - The Homeodomain Resource: 2003 update.
AB  - The Homeodomain Resource is a searchable, curated collection of information for
      the homeodomain protein family. The resource is organized in a compact form and
      provides user-friendly interfaces for both querying the component databases and
      assembling customized datasets. The current release (version 5.0, October 2002)
      contains 1056 full-length homeodomain-containing sequences, 37 experimentally
      derived structures, 81 homeodomain interactions, 84 homeodomain DNA-binding sites
      and 114 homeodomain proteins implicated in human genetic disorders. A new feature
      of this new release is the inclusion of experimentally-derived protein-protein
      interaction data for homeodomain family members. All entries are cross-linked for
      easy retrieval of the original records from source databases. The Homeodomain
      Resource is freely available through the World Wide Web at
      http://research.nhgri.nih.gov/homeodomain/.

PMID- 12520009
TI  - IMGT, the international ImMunoGeneTics database.
AB  - The international ImMunoGeneTics database (IMGT) (http://imgt.cines.fr), is a
      high quality integrated information system specializing in Immunoglobulins (IG),
      T cell Receptors (TR) and Major Histocompatibility Complex (MHC) of human and
      other vertebrates, created in 1989, by the Laboratoire d'ImmunoGenetique
      Moleculaire (LIGM), at the Universite Montpellier II, CNRS, Montpellier, France.
      IMGT provides a common access to standardized data which include nucleotide and
      protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms,
      specificities, 2D and 3D structures. IMGT includes three sequence databases
      (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB)
      with different interfaces (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView), one
      3D structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML
      pages ('IMGT Marie-Paule page') and interactive tools for sequence analysis
      (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/Allele-Align, IMGT/PhyloGene). IMGT
      data are expertly annotated according to the rules of the IMGT Scientific chart,
      based on IMGT-ONTOLOGY. IMGT tools are particularly useful for the analysis of
      the IG and TR repertoires in physiological normal and pathological situations.
      IMGT has important applications in medical research (autoimmune diseases, AIDS,
      leukemias, lymphomas, myelomas), biotechnology related to antibody engineering
      (phage displays, combinatorial libraries) and thera-peutic approaches (graft,
      immunotherapy). IMGT is freely available at http://imgt.cines.fr.

PMID- 12520010
TI  - IMGT/HLA and IMGT/MHC: sequence databases for the study of the major
      histocompatibility complex.
AB  - The IMGT/HLA database (http://www.ebi.ac.uk/imgt/hla) has provided a centralized
      repository for the sequences of the alleles named by the WHO Nomenclature
      Committee for Factors of the HLA System for the past four years. Since its
      initial release the database has grown and is the primary source of information
      for the study of sequences of the human major histocompatibilty complex. The
      initial release of the database contained a limited number of tools. As a result
      of feedback from our users and developments in HLA we have been able to provide
      new tools and facilities. The HLA sequences have also been extended to include
      intron sequences and the 3' and 5' untranslated regions in the alignments and
      also the inclusion of new genes such as MICA. The IMGT/MHC database
      (http://www.ebi.ac.uk/imgt/mhc) was released in March 2002 to provide a similar
      resource for other species. The first release of IMGT/MHC contains the sequences
      of non-human primates (apes, new and old world monkeys), canines and feline
      sequences. Further species will be added shortly and the database aims to become
      the primary source of MHC data for non-human sequences.

PMID- 12520011
TI  - The InterPro Database, 2003 brings increased coverage and new features.
AB  - InterPro, an integrated documentation resource of protein families, domains and
      functional sites, was created in 1999 as a means of amalgamating the major
      protein signature databases into one comprehensive resource. PROSITE, Pfam,
      PRINTS, ProDom, SMART and TIGRFAMs have been manually integrated and curated and
      are available in InterPro for text- and sequence-based searching. The results are
      provided in a single format that rationalises the results that would be obtained
      by searching the member databases individually. The latest release of InterPro
      contains 5629 entries describing 4280 families, 1239 domains, 95 repeats and 15
      post-translational modifications. Currently, the combined signatures in InterPro
      cover more than 74% of all proteins in SWISS-PROT and TrEMBL, an increase of
      nearly 15% since the inception of InterPro. New features of the database include
      improved searching capabilities and enhanced graphical user interfaces for
      visualisation of the data. The database is available via a webserver
      (http://www.ebi.ac.uk/interpro) and anonymous FTP
      (ftp://ftp.ebi.ac.uk/pub/databases/interpro).

PMID- 12520012
TI  - The Lipase Engineering Database: a navigation and analysis tool for protein
      families.
AB  - The Lipase Engineering Database (LED) (http://www.led.uni-stuttgart.de)
      integrates information on sequence, structure, and function of lipases,
      esterases, and related proteins. Sequence data on 806 protein entries are
      assigned to 38 homologous families, which are grouped into 16 superfamilies with
      no global sequence similarity between each other. For each family, multisequence
      alignments are provided with functionally relevant residues annotated. Pre
      calculated phylogenetic trees allow navigation inside superfamilies. Experimental
      structures of 45 proteins are superposed and consistently annotated. The LED has
      been applied to systematically analyze sequence-structure-function relationships
      of this vast and diverse enzyme class. It is a useful tool to identify
      functionally relevant residues apart from the active site residues, and to design
      mutants with desired substrate specificity.

PMID- 12520013
TI  - MitoDrome: a database of Drosophila melanogaster nuclear genes encoding proteins
      targeted to the mitochondrion.
AB  - Mitochondria are organelles present in the cytoplasm of most eukaryotic cells;
      although they have their own DNA, the majority of the proteins necessary for a
      functional mitochondrion are coded by the nuclear DNA and only after
      transcription and translation they are imported in the mitochondrion as proteins.
      The primary role of the mitochondrion is electron transport and oxidative
      phosphorylation. Although it has been studied for a long time, the interest of
      researchers in mitochondria is still alive thanks to the discovery of
      mitochondrial role in apoptosis, aging and cancer. Aim of the MitoDrome database
      is to annotate the Drosophila melanogaster nuclear genes coding for mitochondrial
      proteins in order to contribute to the functional characterization of nuclear
      genes coding for mitochondrial proteins and to knowledge of gene diseases related
      to mitochondrial dysfunctions. Indeed D. melanogaster is one of the most studied
      organisms and a model for the Human genome. Data are derived from the comparison
      of Human mitochondrial proteins versus the Drosophila genome, ESTs and cDNA
      sequence data available in the FlyBase database. Links from the MitoDrome entries
      to the related homologous entries available in MitoNuC will be soon imple-mented.
      The MitoDrome database is available at
      http://bighost.area.ba.cnr.it/BIG/MitoDrome. Data are organised in a flat-file
      format and can be retrieved using the SRS system.

PMID- 12520014
TI  - The Mitochondrial Protein Import Machinery of Plants (MPIMP) database.
AB  - The Mitochondrial Protein Import Machinery of Plants database (MPIMP) is an
      Internet-accessible database containing detailed information on the protein
      import apparatus of plant mitochondria. The Arabidopsis genome was searched for
      com-ponents of the mitochondrial protein import apparatus using components from
      the well-characterized model system of Saccharomyces cerevisiae. Twenty six
      homologues of 34 components could be found, encompassing the essential components
      for the general and carrier import pathways. The database is available through
      the Internet at http://millar3.biochem.uwa.edu.au/~lister/index.html.

PMID- 12520015
TI  - The Nuclear Protein Database (NPD): sub-nuclear localisation and functional
      annotation of the nuclear proteome.
AB  - The Nuclear Protein Database (NPD) is a curated database that contains
      information on more than 1300 vertebrate proteins that are thought, or are known,
      to localise to the cell nucleus. Each entry is annotated with information on
      predicted protein size and isoelectric point, as well as any repeats, motifs or
      domains within the protein sequence. In addition, information on the sub-nuclear
      localisation of each protein is provided and the biological and molecular
      functions are described using Gene Ontology (GO) terms. The database is
      searchable by keyword, protein name, sub-nuclear compartment and protein
      domain/motif. Links to other databases are provided (e.g. Entrez, SWISS-PROT,
      OMIM, PubMed, PubMed Central). Thus, NPD provides a gateway through which the
      nuclear proteome may be explored. The database can be accessed at
      http://npd.hgu.mrc.ac.uk and is updated monthly.

PMID- 12520016
TI  - NRMD: Nuclear Receptor Mutation Database.
AB  - The NRMD is a database for nuclear receptor mutation information. It includes
      mutation information from SWISS-PROT/TrEMBL, several web-based mutation data
      resources, and data extracted from the literature in a fully automatic manner.
      Because it is also possible to add mutations manually, a hundred mutations were
      added for completeness. At present, the NRMD contains information about 893
      mutations in 54 nuclear receptors. A common numbering scheme for all nuclear
      receptors eases the use of the information for many kinds of studies. The NRMD is
      freely available to academia and industry as a stand-alone version at:
      www.receptors.org/NR/.

PMID- 12520017
TI  - PANTHER: a browsable database of gene products organized by biological function,
      using curated protein family and subfamily classification.
AB  - The PANTHER database was designed for high-throughput analysis of protein
      sequences. One of the key features is a simplified ontology of protein function,
      which allows browsing of the database by biological functions. Biologist curators
      have associated the ontology terms with groups of protein sequences rather than
      individual sequences. Statistical models (Hidden Markov Models, or HMMs) are
      built from each of these groups. The advantage of this approach is that new
      sequences can be automatically classified as they become available. To ensure
      accurate functional classification, HMMs are constructed not only for families,
      but also for functionally distinct subfamilies. Multiple sequence alignments and
      phylogenetic trees, including curator-assigned information, are available for
      each family. The current version of the PANTHER database includes training
      sequences from all organisms in the GenBank non-redundant protein database, and
      the HMMs have been used to classify gene products across the entire genomes of
      human, and Drosophila melanogaster. The ontology terms and protein families and
      subfamilies, as well as Drosophila gene c;assifications, can be browsed and
      searched for free. Due to outstanding contractual obligations, access to human
      gene classifications and to protein family trees and multiple sequence alignments
      will temporarily require a nominal registration fee. PANTHER is publicly
      available on the web at http://panther.celera.com.

PMID- 12520018
TI  - The PlantsP and PlantsT Functional Genomics Databases.
AB  - PlantsP and PlantsT allow users to quickly gain a global understanding of plant
      phosphoproteins and plant membrane transporters, respectively, from evolutionary
      relationships to biochemical function as well as a deep understanding of the
      molecular biology of individual genes and their products. As one database with
      two functionally different web interfaces, PlantsP and PlantsT are curated plant
      specific databases that combine sequence-derived information with experimental
      functional-genomics data. PlantsP focuses on proteins involved in the
      phosphorylation process (i.e., kinases and phosphatases), whereas PlantsT focuses
      on membrane transport proteins. Experimentally, PlantsP provides a resource for
      information on a collection of T-DNA insertion mutants (knockouts) in each kinase
      and phosphatase, primarily in Arabidopsis thaliana, and PlantsT uniquely combines
      experimental data regarding mineral composition (derived from inductively coupled
      plasma atomic emission spectroscopy) of mutant and wild-type strains. Both
      databases provide extensive information on motifs and domains, detailed
      information contributed by individual experts in their respective fields, and
      descriptive information drawn directly from the literature. The databases
      incorporate a unique user annotation and review feature aimed at acquiring expert
      annotation directly from the plant biology community. PlantsP is available at
      http://plantsp.sdsc.edu and PlantsT is available at http://plantst.sdsc.edu.

PMID- 12520019
TI  - The Protein Information Resource.
AB  - The Protein Information Resource (PIR) is an integrated public resource of
      protein informatics that supports genomic and proteomic research and scientific
      discovery. PIR maintains the Protein Sequence Database (PSD), an annotated
      protein database containing over 283 000 sequences covering the entire taxonomic
      range. Family classification is used for sensitive identification, consistent
      annotation, and detection of annotation errors. The superfamily curation defines
      signature domain architecture and categorizes memberships to improve automated
      classification. To increase the amount of experimental annotation, the PIR has
      developed a bibliography system for literature searching, mapping, and user
      submission, and has conducted retrospective attribution of citations for
      experimental features. PIR also maintains NREF, a non-redundant reference
      database, and iProClass, an integrated database of protein family, function, and
      structure information. PIR-NREF provides a timely and comprehensive collection of
      protein sequences, currently consisting of more than 1 000 000 entries from PIR
      PSD, SWISS-PROT, TrEMBL, RefSeq, GenPept, and PDB. The PIR web site
      (http://pir.georgetown.edu) connects data analysis tools to underlying databases
      for information retrieval and knowledge discovery, with functionalities for
      interactive queries, combinations of sequence and text searches, and sorting and
      visual exploration of search results. The FTP site provides free download for PSD
      and NREF biweekly releases and auxiliary databases and files.

PMID- 12520020
TI  - ProtoNet: hierarchical classification of the protein space.
AB  - The ProtoNet site provides an automatic hierarchical clustering of the SWISS-PROT
      protein database. The clustering is based on an all-against-all BLAST similarity
      search. The similarities' E-score is used to perform a continuous bottom-up
      clustering process by applying alternative rules for merging clusters. The
      outcome of this clustering process is a classification of the input proteins into
      a hierarchy of clusters of varying degrees of granularity. ProtoNet (version 1.3)
      is accessible in the form of an interactive web site at
      http://www.protonet.cs.huji.ac.il. ProtoNet provides navigation tools for
      monitoring the clustering process with a vertical and horizontal view. Each
      cluster at any level of the hierarchy is assigned with a statistical index,
      indicating the level of purity based on biological keywords such as those
      provided by SWISS-PROT and InterPro. ProtoNet can be used for function
      prediction, for defining superfamilies and subfamilies and for large-scale
      protein annotation purposes.

PMID- 12520021
TI  - RTKdb: database of Receptor Tyrosine Kinase.
AB  - Receptor Tyrosine Kinases (RTK) are transmembrane receptors specifically found in
      metazoans. They represent an excellent model for studying evolution of cellular
      processes in metazoans because they encompass large families of modular proteins
      and belong to a major family of contingency generating molecules in eukaryotic
      cells: the protein kinases. Because tyrosine kinases have been under close
      scrutiny for many years in various species, they are associated with a wealth of
      information, mainly in mammals. Presently, most categories of RTK were identified
      in mammals, but in a near future other model species will be sequenced, and will
      bring us RTKs from other metazoan clades. Thus, collecting RTK sequences would
      provide a good starting point as a new model for comparative and evolutionary
      studies applying to multigene families. In this context, we are developing the
      Receptor Tyrosine Kinase database (RTKdb), which is the only database on tyrosine
      kinase receptors presently available. In this database, protein sequences from
      eight model metazoan species are organized under the format previously used for
      the HOVERGEN, HOBACGEN and NUREBASE systems. RTKdb can be accessed through the
      PBIL (Pole Bioinformatique Lyonnais) World Wide Web server at http://pbil.univ
      lyon1.fr/RTKdb/, or through the FamFetch graphical user interface available at
      the same address.

PMID- 12520022
TI  - SDAP: database and computational tools for allergenic proteins.
AB  - SDAP (Structural Database of Allergenic Proteins) is a web server that provides
      rapid, cross-referenced access to the sequences, structures and IgE epitopes of
      allergenic proteins. The SDAP core is a series of CGI scripts that process the
      user queries, interrogate the database, perform various computations related to
      protein allergenic determinants and prepare the output HTML pages. The database
      component of SDAP contains information about the allergen name, source, sequence,
      structure, IgE epitopes and literature references and easy links to the major
      protein (PDB, SWISS-PROT/TrEMBL, PIR-ALN, NCBI Taxonomy Browser) and literature
      (PubMed, MEDLINE) on-line servers. The computational component in SDAP uses an
      original algorithm based on conserved properties of amino acid side chains to
      identify regions of known allergens similar to user-supplied peptides or selected
      from the SDAP database of IgE epitopes. This and other bioinformatics tools can
      be used to rapidly determine potential cross-reactivities between allergens and
      to screen novel proteins for the presence of IgE epitopes they may share with
      known allergens. SDAP is available via the World Wide Web at
      http://fermi.utmb.edu/SDAP/.

PMID- 12520023
TI  - SRPDB: Signal Recognition Particle Database.
AB  - The Signal Recognition Particle Database (SRPDB) at
      http://psyche.uthct.edu/dbs/SRPDB/SRPDB.html and
      http://bio.lundberg.gu.se/dbs/SRPDB/SRPDB.html assists in the better
      understanding of the structure and function of the signal recognition particle
      (SRP), a ribonucleoprotein complex that recognizes signal sequences as they
      emerge from the ribosome. SRPDB provides alphabetically and phylogenetically
      ordered lists of SRP RNA and SRP protein sequences. The SRP RNA alignment
      emphasizes base pairs supported by comparative sequence analysis to derive
      accurate SRP RNA secondary structures for each species. This release includes a
      total of 181 SRP RNA sequences, 7 protein SRP9, 11 SRP14, 31 SRP19, 113 SRP54
      (Ffh), 9 SRP68 and 12 SRP72 sequences. There are 44 new sequences of the SRP
      receptor alpha subunit and its FtsY homolog (a total of 99 entries). Additional
      data are provided for polypeptides with established or potential roles in SRP
      mediated protein targeting, such as the beta subunit of SRP receptor, Flhf, Hbsu
      and cpSRP43. Also available are motifs for the identification of new SRP RNA
      sequences, 2D representations, three-dimensional models in PDB format, and links
      to the high-resolution structures of several SRP components. New to this version
      of SRPDB is the introduction of a relational database system and a SRP RNA
      prediction server (SRP-Scan) which allows the identification of SRP RNAs within
      genome sequences and also generates secondary structure diagrams.

PMID- 12520024
TI  - The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003.
AB  - The SWISS-PROT protein knowledgebase (http://www.expasy.org/sprot/ and
      http://www.ebi.ac.uk/swissprot/) connects amino acid sequences with the current
      knowledge in the Life Sciences. Each protein entry provides an interdisciplinary
      overview of relevant information by bringing together experimental results,
      computed features and sometimes even contradictory conclusions. Detailed
      expertise that goes beyond the scope of SWISS-PROT is made available via direct
      links to specialised databases. SWISS-PROT provides annotated entries for all
      species, but concentrates on the annotation of entries from human (the HPI
      project) and other model organisms to ensure the presence of high quality
      annotation for representative members of all protein families. Part of the
      annotation can be transferred to other family members, as is already done for
      microbes by the High-quality Automated and Manual Annotation of microbial
      Proteomes (HAMAP) project. Protein families and groups of proteins are regularly
      reviewed to keep up with current scientific findings. Complementarily, TrEMBL
      strives to comprise all protein sequences that are not yet represented in SWISS
      PROT, by incorporating a perpetually increasing level of mostly automated
      annotation. Researchers are welcome to contribute their knowledge to the
      scientific community by submitting relevant findings to SWISS-PROT at swiss
      prot@expasy.org.

PMID- 12520025
TI  - The TIGRFAMs database of protein families.
AB  - TIGRFAMs is a collection of manually curated protein families consisting of
      hidden Markov models (HMMs), multiple sequence alignments, commentary, Gene
      Ontology (GO) assignments, literature references and pointers to related
      TIGRFAMs, Pfam and InterPro models. These models are designed to support both
      automated and manually curated annotation of genomes. TIGRFAMs contains models of
      full-length proteins and shorter regions at the levels of superfamilies,
      subfamilies and equivalogs, where equivalogs are sets of homologous proteins
      conserved with respect to function since their last common ancestor. The scope of
      each model is set by raising or lowering cutoff scores and choosing members of
      the seed alignment to group proteins sharing specific function (equivalog) or
      more general properties. The overall goal is to provide information with maximum
      utility for the annotation process. TIGRFAMs is thus complementary to Pfam, whose
      models typically achieve broad coverage across distant homologs but end at the
      boundaries of conserved structural domains. The database currently contains over
      1600 protein families. TIGRFAMs is available for searching or downloading at
      www.tigr.org/TIGRFAMs.

PMID- 12520026
TI  - TRANSFAC: transcriptional regulation, from patterns to profiles.
AB  - The TRANSFAC database on eukaryotic transcriptional regulation, comprising data
      on transcription factors, their target genes and regulatory binding sites, has
      been extended and further developed, both in number of entries and in the scope
      and structure of the collected data. Structured fields for expression patterns
      have been introduced for transcription factors from human and mouse, using the
      CYTOMER database on anatomical structures and developmental stages. The
      functionality of Match, a tool for matrix-based search of transcription factor
      binding sites, has been enhanced. For instance, the program now comes along with
      a number of tissue-(or state-)specific profiles and new profiles can be created
      and modified with Match Profiler. The GENE table was extended and gained in
      importance, containing amongst others links to LocusLink, RefSeq and OMIM now.
      Further, (direct) links between factor and target gene on one hand and between
      gene and encoded factor on the other hand were introduced. The TRANSFAC public
      release is available at http://www.gene-regulation.com. For yeast an additional
      release including the latest data was made available separately as TRANSFAC
      Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download
      versions are available at http://www.biobase.de:8080/index.html.

PMID- 12520027
TI  - Active Sequences Collection (ASC) database: a new tool to assign functions to
      protein sequences.
AB  - Active Sequences Collection (ASC) is a collection of amino acid sequences, with
      an unique feature: only short sequences are collected, with a demonstrated
      biological activity. The current version of ASC consists of three sections:
      DORRS, a collection of active RGD-containing peptides; TRANSIT, a collection of
      protein regions active as substrates of transglutaminase enzyme (TGase), and BAC,
      a collection of short peptides with demonstrated biological activity. Literature
      references for each entry are reported, as well as cross references to other
      databases, when available. The current version of ASC includes more than 800
      different entries. The main scope of this collection is to offer a new tool to
      investigate the structural features of protein active sites, additionally to
      similarity searches against large protein databases or searching for known
      functional patterns. ASC database is available at the web address
      http://crisceb.unina2.it/ASC/ which also offers a dedicated query interface to
      compare user-defined protein sequences with the database, as well as an updating
      interface to allow contribution of new referenced active sequences.

PMID- 12520028
TI  - CDD: a curated Entrez database of conserved domain alignments.
AB  - The Conserved Domain Database (CDD) is now indexed as a separate database within
      the Entrez system and linked to other Entrez databases such as MEDLINE(R). This
      allows users to search for domain types by name, for example, or to view the
      domain architecture of any protein in Entrez's sequence database. CDD can be
      accessed on the WorldWideWeb at
      http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=cdd. Users may also employ the
      CD-Search service to identify conserved domains in new sequences, at
      http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. CD-Search results, and pre
      computed links from Entrez's protein database, are calculated using the RPS-BLAST
      algorithm and Position Specific Score Matrices (PSSMs) derived from CDD
      alignments. CD-Searches are also run by default for protein-protein queries
      submitted to BLAST(R) at http://www.ncbi.nlm.nih.gov/BLAST. CDD mirrors the
      publicly available domain alignment collections SMART and PFAM, and now also
      contains alignment models curated at NCBI. Structure information is used to
      identify the core substructure likely to be present in all family members, and to
      produce sequence alignments consistent with structure conservation. This
      alignment model allows NCBI curators to annotate 'columns' corresponding to
      functional sites conserved among family members.

PMID- 12520029
TI  - Improvements to CluSTr: the database of SWISS-PROT+TrEMBL protein clusters.
AB  - The CluSTr database (http://www.ebi.ac.uk/clustr/) offers an automatic
      classification of SWISS-PROT+TrEMBL proteins into groups of related proteins. The
      clustering is based on analysis of all pair-wise sequence comparisons between
      proteins using the Smith-Waterman algorithm. The analysis, carried out on
      different levels of protein similarity, yields a hierarchical organization of
      clusters. Information about domain content of the clustered proteins is provided
      via the InterPro resource. The introduced InterPro 'condensed graphical view'
      simplifies the visual analysis of represented domain architectures. Integrated
      applications allow users to visualize and edit multiple alignments and build
      sequence divergence trees. Links to the relevant structural data in Protein Data
      Bank (PDB) and Homology derived Secondary Structure of Proteins (HSSP) are also
      provided.

PMID- 12520030
TI  - iProClass: an integrated database of protein family, function and structure
      information.
AB  - The iProClass database provides comprehensive, value-added descriptions of
      proteins and serves as a framework for data integration in a distributed
      networking environment. The protein information in iProClass includes family
      relationships as well as structural and functional classifications and features.
      The current version consists of about 830 000 non-redundant PIR-PSD, SWISS-PROT,
      and TrEMBL proteins organized with more than 36 000 PIR superfamilies, 145 000
      families, 4000 domains, 1300 motifs and 550 000 FASTA similarity clusters. It
      provides rich links to over 50 database of protein sequences, families, functions
      and pathways, protein-protein interactions, post-translational modifications,
      protein expressions, structures and structural classifications, genes and
      genomes, ontologies, literature and taxonomy. Protein and superfamily summary
      reports present extensive annotation information and include membership
      statistics and graphical display of domains and motifs. iProClass employs an open
      and modular architecture for interoperability and scalability. It is implemented
      in the Oracle object-relational database system and is updated biweekly. The
      database is freely accessible from the web site at
      http://pir.georgetown.edu/iproclass/ and searchable by sequence or text string.
      The data integration in iProClass supports exploration of protein relationships.
      Such knowledge is fundamental to the understanding of protein evolution,
      structure and function and crucial to functional genomic and proteomic research.

PMID- 12520031
TI  - NESbase version 1.0: a database of nuclear export signals.
AB  - Protein export from the nucleus is often mediated by a Leucine-rich Nuclear
      Export Signal (NES). NESbase is a database of experimentally validated Leucine
      rich NESs curated from literature. These signals are not annotated in databases
      such as SWISS-PROT, PIR or PROSITE. Each NESbase entry contains information of
      whether NES was shown to be necessary and/or sufficient for export, and whether
      the export was shown to be mediated by the export receptor CRM1. The compiled
      information was used to make a sequence logo of the Leucine-rich NESs, displaying
      the conservation of amino acids within a window of 25 residues. Surprisingly,
      only 36% of the sequences used for the logo fit the widely accepted NES consensus
      L-x(2,3)-[LIVFM]-x(2,3)-L-x-[LI]. The database is available online at
      http://www.cbs.dtu.dk/databases/NESbase/.

PMID- 12520032
TI  - NLSdb: database of nuclear localization signals.
AB  - NLSdb is a database of nuclear localization signals (NLSs) and of nuclear
      proteins. NLSs are short stretches of residues mediating transport of nuclear
      proteins into the nucleus. The database contains 114 experimentally determined
      NLSs that were obtained through an extensive literature search. Using 'in silico
      mutagenesis' this set was extended to 308 experimental and potential NLSs. This
      final set matched over 43% of all known nuclear proteins and matches no currently
      known non-nuclear protein. NLSdb contains over 6000 predicted nuclear proteins
      and their targeting signals from the PDB and SWISS-PROT/TrEMBL databases. The
      database also contains over 12 500 predicted nuclear proteins from six entirely
      sequenced eukaryotic proteomes (Homo sapiens, Mus musculus, Drosophila
      melanogaster, Caenorhabditis elegans, Arabidopsis thaliana and Saccharomyces
      cerevisiae). NLS motifs often co-localize with DNA-binding regions. This
      observation was used to also annotate over 1500 DNA-binding proteins. NLSdb can
      be accessed via the web site: http://cubic.bioc.columbia.edu/db/NLSdb/.

PMID- 12520034
TI  - The SBASE domain sequence library, release 10: domain architecture prediction.
AB  - SBASE (http://www.icgeb.trieste.it/sbase) is an on-line collection of protein
      domain sequences and related computational tools designed to facilitate detection
      of domain homologies based on simple database search. The 10th 'jubilee release'
      of the SBASE library of protein domain sequences contains 1 052 904 protein
      sequence segments annotated by structure, function, ligand-binding or cellular
      topology, clustered into over 6000 domain groups. Domain identification and
      functional prediction are based on a comparison of BLAST search outputs with a
      knowledge base of biologically significant similarities extracted from known
      domain groups. The knowledge base is generated automatically for each domain
      group from the comparison of within-group ('self') and out-of-group ('non-self')
      similarities. This is a memory-based approach wherein group-specific similarity
      functions are automatically learned from the database.

PMID- 12520033
TI  - PRINTS and its automatic supplement, prePRINTS.
AB  - The PRINTS database houses a collection of protein fingerprints. These may be
      used to assign uncharacterised sequences to known families and hence to infer
      tentative functions. The September 2002 release (version 36.0) includes 1800
      fingerprints, encoding approximately 11 000 motifs, covering a range of globular
      and membrane proteins, modular polypeptides and so on. In addition to its
      continued steady growth, we report here the development of an automatic
      supplement, prePRINTS, designed to increase the coverage of the resource and
      reduce some of the manual burdens inherent in its maintenance. The databases are
      accessible for interrogation and searching at
      http://www.bioinf.man.ac.uk/dbbrowser/PRINTS/.

PMID- 12520035
TI  - TMPDB: a database of experimentally-characterized transmembrane topologies.
AB  - TMPDB is a database of experimentally-characterized transmembrane (TM)
      topologies. TMPDB release 6.2 contains a total of 302 TM protein sequences, in
      which 276 are alpha-helical sequences, 17 beta-stranded, and 9 alpha-helical
      sequences with short pore-forming helices buried in the membrane. The TM
      topologies in TMPDB were determined experimentally by means of X-ray
      crystallography, NMR, gene fusion technique, substituted cysteine accessibility
      method, N-linked glycosylation experiment and other biochemical methods. TMPDB
      would be useful as a test and/or training dataset in improving the proposed TM
      topology prediction methods or developing novel methods with higher performance,
      and as a guide for both the bioinformaticians and biologists to better understand
      TM proteins. TMPDB and its subsets are freely available at the following web
      site: http://bioinfo.si.hirosaki-u.ac.jp/~TMPDB/.

PMID- 12520036
TI  - PEP: Predictions for Entire Proteomes.
AB  - PEP is a database of Predictions for Entire Proteomes. The database contains
      summaries of analyses of protein sequences from a range of organisms representing
      all three major kingdoms of life: eukaryotes, prokaryotes and archaea. All
      proteins publicly available for organisms were aligned against SWISS-PROT, TrEMBL
      and PDB. Additionally, the following annotations are provided: secondary
      structure, transmembrane helices, coiled coils, regions of low complexity, signal
      peptides, PROSITE motifs, nuclear localization signals and classes of cellular
      function. Proteins that contain long regions without regular secondary structure
      are also identified. We have produced a related database of structural domain
      like fragments derived from PEP and clusters based on homology between all
      fragments. The PEP database, fragments and clusters are distributed freely as a
      set of flat files and have been integrated into SRS. The PEP group of databases
      can be accessed from: http://cubic.bioc.columbia.edu/pep.

PMID- 12520037
TI  - The Proteome Analysis database: a tool for the in silico analysis of whole
      proteomes.
AB  - The Proteome Analysis database (http://www.ebi.ac.uk/proteome/) has been
      developed by the Sequence Database Group at EBI utilizing existing resources and
      providing comparative analysis of the predicted protein coding sequences of the
      complete genomes of bacteria, archeae and eukaryotes. Three main projects are
      used, InterPro, CluSTr and GO Slim, to give an overview on families, domains,
      sites, and functions of the proteins from each of the complete genomes. Complete
      proteome analysis is available for a total of 89 proteome sets. A specifically
      designed application enables InterPro proteome comparisons for any one proteome
      against any other one or more of the proteomes in the database.

PMID- 12520038
TI  - REBASE: restriction enzymes and methyltransferases.
AB  - REBASE contains comprehensive information about restriction enzymes, DNA
      methyltransferases and related proteins such as nicking enzymes, specificity
      subunits and control proteins. It contains published and unpublished references,
      recognition and cleavage sites, isoschizomers, commercial availability, crystal
      and sequence data. Homing endonucleases are also included. REBASE contains the
      most complete and up-to-date information about the methylation sensitivity of
      restriction endonucleases. In addition, there is extensive information about the
      known and putative restriction-modification (R-M) systems in more than 100
      sequenced bacterial and archaeal genomes. The data is available on the web
      (http://rebase.neb.com/rebase/rebase.html), through ftp (ftp.neb.com) and as
      monthly updates via email.

PMID- 12520039
TI  - ARED 2.0: an update of AU-rich element mRNA database.
AB  - The Adenylate Uridylate (AU)-Rich Element Database, ARED-mRNA version 2.0,
      contains information not present in the previous ARED. This includes additional
      data entries, new information and links to Unigene, LocusLink, RefSeq records and
      mouse homologue data. An ARE consensus sequence specific to the 3'UTR is the
      basis of ARED that demonstrated two important findings: (i) AREs are present in a
      large, previously unrecognized set of human mRNAs; and (ii) ARE-mRNAs encode
      proteins of diverse functions which are largely involved in early and transient
      biological responses. In this update, we have modified the strategy for
      identifying ARE-mRNA in order to systematically deal with inconsistencies of
      molecule type and mRNA region in GenBank records. Potential uses for the ARED in
      functional genomics are also given. The database is accessible via the web,
      http://rc.kfshrc.edu.sa/ared, with a new querying system that allows searching
      ARE-mRNAs by any public database identifier or name. The ARED website also
      contains relevant links to uses for the ARED.

PMID- 12520040
TI  - Database for mobile group II introns.
AB  - Group II introns are self-splicing RNAs and retroelements found in bacteria and
      lower eukaryotic organelles. During the past several years, they have been
      uncovered in surprising numbers in bacteria due to the genome sequencing
      projects; however, most of the newly sequenced introns are not correctly
      identified. We have initiated an ongoing web site database for mobile group II
      introns in order to provide correct information on the introns, particularly in
      bacteria. Information in the web site includes: (1) introductory information on
      group II introns; (2) detailed information on subfamilies of intron RNA
      structures and intron-encoded proteins; (3) a listing of identified introns with
      correct boundaries, RNA secondary structures and other detailed information; and
      (4) phylogenetic and evolutionary information. The comparative data should
      facilitate study of the function, spread and evolution of group II introns. The
      database can be accessed at http://www.fp.ucalgary.ca/group2introns/.

PMID- 12520041
TI  - IRESdb: the Internal Ribosome Entry Site database.
AB  - Internal Ribosome Entry Sites (IRES) are cis-acting RNA sequences able to mediate
      internal entry of the 40S ribosomal subunit on some eukaryotic and viral
      messenger RNAs upstream of a translation initiation codon. These sequences are
      very diverse and are present in a growing list of mRNAs. Novel IRES sequences
      continue to be added to public databases every year and the list of unknown
      IRESes is certainly still very large. The IRES database is a comprehensive WWW
      resource for internal ribosome entry sites and presents currently available
      general information as well as detailed data for each IRES. It is a searchable,
      periodically updated collection of IRES RNA sequences. Sequences are presented in
      FASTA form and hotlinked to NCBI GenBank files. Several subsets of data are
      classified according to the viral taxon (for viral IRESes), to the gene product
      function (for cellular IRESes), to the possible cellular regulation or to the
      trans-acting factor that mediates IRES function. This database is accessible at
      http://ifr31w3.toulouse.inserm.fr/IRESdatabase/.

PMID- 12520042
TI  - Noncoding regulatory RNAs database.
AB  - The noncoding RNAs database is a collection of currently available sequence data
      on RNAs, which have no protein-coding capacity and have been implicated in
      regulation of cellular processes. The RNAs included in the database form very
      heterogenous group of molecules that act on different levels of information
      transmission in the cell. It includes RNAs acting on the level of chromatin
      structure, transcriptional and translational regulation of gene expression,
      modulation of protein function and regulation of subcellular distribution of RNAs
      and proteins. Those RNAs, with potential regulatory functions have been
      identified in prokaryotic, animal and plant cells. The database can be accessed
      at http://biobases.ibch.poznan.pl/ncRNA/.

PMID- 12520043
TI  - Plant snoRNA database.
AB  - The Plant snoRNA database (http://www.scri.sari.ac.uk/plant_snoRNA/) provides
      information on small nucleolar RNAs from Arabidopsis and eighteen other plant
      species. Information includes sequences, expression data, methylation and
      pseudouridylation target modification sites, initial gene organization
      (polycistronic, single gene and intronic) and the number of gene variants. The
      Arabidopsis information is divided into box C/D and box H/ACA snoRNAs, and within
      each of these groups, by target sites in rRNA, snRNA or unknown. Alignments of
      orthologous genes and gene variants from different plant species are available
      for many snoRNA genes. Plant snoRNA genes have been given a standard
      nomenclature, designed wherever possible, to provide a consistent identity with
      yeast and human orthologues.

PMID- 12520044
TI  - PLMItRNA, a database on the heterogeneous genetic origin of mitochondrial tRNA
      genes and tRNAs in photosynthetic eukaryotes.
AB  - The updated version of PLMItRNA reports information and multialignments on 609
      genes and 34 tRNA molecules active in the mitochondria of Viridiplantae (27
      Embryophyta and 10 Chlorophyta), and photosynthetic algae (one Cryptophyta, four
      Rhodophyta and two Stramenopiles). Colour-code based tables reporting the
      different genetic origin of identified genes allow hyper-textual link to single
      entries. Promoter sequences identified for tRNA genes in the mitochondrial
      genomes of Angiospermae are also reported. The PLMItRNA database is accessible at
      http://bighost.area.ba.cnr.it/PLMItRNA/.

PMID- 12520045
TI  - Rfam: an RNA family database.
AB  - Rfam is a collection of multiple sequence alignments and covariance models
      representing non-coding RNA families. Rfam is available on the web in the UK at
      http://www.sanger.ac.uk/Software/Rfam/ and in the US at http://rfam.wustl.edu/.
      These websites allow the user to search a query sequence against a library of
      covariance models, and view multiple sequence alignments and family annotation.
      The database can also be downloaded in flatfile form and searched locally using
      the INFERNAL package (http://infernal.wustl.edu/). The first release of Rfam
      (1.0) contains 25 families, which annotate over 50 000 non-coding RNA genes in
      the taxonomic divisions of the EMBL nucleotide database.

PMID- 12520046
TI  - The Ribosomal Database Project (RDP-II): previewing a new autoaligner that allows
      regular updates and the new prokaryotic taxonomy.
AB  - The Ribosomal Database Project-II (RDP-II) pro-vides data, tools and services
      related to ribosomal RNA sequences to the research community. Through its website
      (http://rdp.cme.msu.edu), RDP-II offers aligned and annotated rRNA sequence data,
      analysis services, and phylogenetic inferences (trees) derived from these data.
      RDP-II release 8.1 contains 16 277 prokaryotic, 5201 eukaryotic, and 1503
      mitochondrial small subunit rRNA sequences in aligned and annotated format. The
      current public beta release of 9.0 debuts a new regularly updated alignment of
      over 50 000 annotated (eu)bacterial sequences. New analysis services include a
      sequence search and selection tool (Hierarchy Browser) and a phylogenetic tree
      building and visualization tool (Phylip Interface). A new interactive tutorial
      guides users through the basics of rRNA sequence analysis. Other services include
      probe checking, phylogenetic placement of user sequences, screening of users'
      sequences for chimeric rRNA sequences, automated alignment, production of
      similarity matrices, and services to plan and analyze terminal restriction
      fragment polymorphism (T-RFLP) experiments. The RDP-II email address for
      questions or comments is rdpstaff@msu.edu.

PMID- 12520047
TI  - SubViral RNA: a database of the smallest known auto-replicable RNA species.
AB  - We describe here the establishment of an online database containing a large
      number of sequences and related data on viroids, viroid-like RNAs and human
      hepatitis delta virus (vHDV) in a customizable and user-friendly format. This
      database is available on the World Wide Web at
      http://penelope.med.usherb.ca/subviral.

PMID- 12520048
TI  - tmRDB (tmRNA database).
AB  - Maintained at the University of Texas Health Science Center at Tyler, Texas, the
      tmRNA database (tmRDB) is accessible at the URL
      http://psyche.uthct.edu/dbs/tmRDB/tmRDB.html with mirror sites located at Auburn
      University, Auburn, Alabama (http://www.ag.auburn.edu/mirror/tmRDB/) and the
      Bioinformatics Research Center, Aarhus, Denmark (http://www.bioinf.au.dk/tmRDB/).
      The tmRDB collects and distributes information relevant to the study of tmRNA. In
      trans-translation, this molecule combines properties of tRNA and mRNA and binds
      several proteins to form the tmRNP. Related RNPs are likely to be functional in
      all bacteria. In this release of tmRDB, 186 new entries from 10 bacterial groups
      for a total of 274 tmRNA sequences have been added. Lists of the tmRNAs and the
      corresponding tmRNA-encoded tag-peptides are presented in alphabetical and
      phylogenetic order. The tmRNA sequences are aligned manually, assisted by
      computational tools, to determine base pairs supported by comparative sequence
      analysis. The tmRNA alignment, available in a variety of formats, provides the
      basis for the secondary and tertiary structure of each tmRNA molecule. Three
      dimensional models of the tmRNAs and their associated proteins in PDB format give
      evidence for the recent progress that has been made in the understanding of tmRNP
      structure and function.

PMID- 12520049
TI  - CADB: Conformation Angles DataBase of proteins.
AB  - Conformation Angles DataBase (CADB) provides an online resource to access data on
      conformation angles (both main-chain and side-chain) of protein structures in two
      data sets corresponding to 25% and 90% sequence identity between any two
      proteins, available in the Protein Data Bank. In addition, the database contains
      the necessary crystallographic parameters. The package has several flexible
      options and display facilities to visualize the main-chain and side-chain
      conformation angles for a particular amino acid residue. The package can also be
      used to study the interrelationship between the main-chain and side-chain
      conformation angles. A web based JAVA graphics interface has been deployed to
      display the user interested information on the client machine. The database is
      being updated at regular intervals and can be accessed over the World Wide Web
      interface at the following URL: http://144.16.71.148/cadb/.

PMID- 12520050
TI  - The CATH database: an extended protein family resource for structural and
      functional genomics.
AB  - The CATH database of protein domain structures
      (http://www.biochem.ucl.ac.uk/bsm/cath_new) currently contains 34 287 domain
      structures classified into 1383 superfamilies and 3285 sequence families. Each
      structural family is expanded with domain sequence relatives recruited from
      GenBank using a variety of efficient sequence search protocols and reliable
      thresholds. This extended resource, known as the CATH-protein family database
      (CATH-PFDB) contains a total of 310 000 domain sequences classified into 26 812
      sequence families. New sequence search protocols have been designed, based on
      these intermediate sequence libraries, to allow more regular updating of the
      classification. Further developments include the adaptation of a recently
      developed method for rapid structure comparison, based on secondary structure
      matching, for domain boundary assignment. The philosophy behind CATHEDRAL is the
      recognition of recurrent folds already classified in CATH. Benchmarking of
      CATHEDRAL, using manually validated domain assignments, demonstrated that 43% of
      domains boundaries could be completely automatically assigned. This is an
      improvement on a previous consensus approach for which only 10-20% of domains
      could be reliably processed in a completely automated fashion. Since domain
      boundary assignment is a significant bottleneck in the classification of new
      structures, CATHEDRAL will also help to increase the frequency of CATH updates.

PMID- 12520051
TI  - DSMM: a Database of Simulated Molecular Motions.
AB  - We describe a Database of Simulated Molecular Motions (DSMM). This database is
      designed to serve as a single searchable site for locating movies and animations
      from simulations of biomolecules. DSMM is accessible via a webserver at:
      http://projects.villa-bosch.de/mcm/database/dsmm.

PMID- 12520052
TI  - E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.
AB  - The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd)
      is designed to be a single access point for protein and nucleic acid structures
      and related information. The database is derived from Protein Data Bank (PDB)
      entries. Relational database technologies are used in a comprehensive cleaning
      procedure to ensure data uniformity across the whole archive. The search database
      contains an extensive set of derived properties, goodness-of-fit indicators, and
      links to other EBI databases including InterPro, GO, and SWISS-PROT, together
      with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is
      available, coupled with a fast secondary structure domain search tool.

PMID- 12520053
TI  - Enlarged FAMSBASE: protein 3D structure models of genome sequences for 41
      species.
AB  - Enlarged FAMSBASE is a relational database of comparative protein structure
      models for the whole genome of 41 species, presented in the GTOP database. The
      models are calculated by Full Automatic Modeling System (FAMS). Enlarged FAMSBASE
      provides a wide range of query keys, such as name of ORF (open reading frame),
      ORF keywords, Protein Data Bank (PDB) ID, PDB heterogen atoms and sequence
      similarity. Heterogen atoms in PDB include cofactors, ligands and other factors
      that interact with proteins, and are a good starting point for analyzing
      interactions between proteins and other molecules. The data may also work as a
      template for drug design. The present number of ORFs with protein 3D models in
      FAMSBASE is 183 805, and the database includes an average of three models for
      each ORF. FAMSBASE is available at http://famsbase.bio.nagoya-u.ac.jp/famsbase/.

PMID- 12520054
TI  - Gene3D: structural assignments for the biologist and bioinformaticist alike.
AB  - The Gene3D database (http://www.biochem.ucl.ac.uk/bsm/cath_new/Gene3D/) provides
      structural assignments for genes within complete genomes. These are available via
      the internet from either the World Wide Web or FTP. Assignments are made using
      PSI-BLAST and subsequently processed using the DRange protocol. The DRange
      protocol is an empirically benchmarked method for assessing the validity of
      structural assignments made using sequence searching methods where appropriate
      assignment statistics are collected and made available. Gene3D links assignments
      to their appropriate entries in relevent structural and classification resources
      (PDBsum, CATH database and the Dictionary of Homologous Superfamilies). Release
      2.0 of Gene3D includes 62 genomes, 2 eukaryotes, 10 archaea and 40 bacteria.
      Currently, structural assignments can be made for between 30 and 40 percent of
      any given genome. In any genome, around half of those genes assigned a structural
      domain are assigned a single domain and the other half of the genes are assigned
      multiple structural domains. Gene3D is linked to the CATH database and is updated
      with each new update of CATH.

PMID- 12520055
TI  - MMDB: Entrez's 3D-structure database.
AB  - Three-dimensional structures are now known within most protein families and it is
      likely, when searching a sequence database, that one will identify a homolog of
      known structure. The goal of Entrez's 3D-structure database is to make structure
      information and the functional annotation it can provide easily accessible to
      molecular biologists. To this end, Entrez's search engine provides several
      powerful features: (i) links between databases, for example between a protein's
      sequence and structure; (ii) pre-computed sequence and structure neighbors; and
      (iii) structure and sequence/structure alignment visualization. Here, we focus on
      a new feature of Entrez's Molecular Modeling Database (MMDB): Graphical summaries
      of the biological annotation available for each 3D structure, based on the
      results of automated comparative analysis. MMDB is available at:
      http://www.ncbi.nlm.nih.gov/Entrez/structure.html.

PMID- 12520056
TI  - MolMovDB: analysis and visualization of conformational change and structural
      flexibility.
AB  - The Database of Macromolecular Movements (http://MolMovDB.org) is a collection of
      data and software pertaining to flexibility in protein and RNA structures. The
      database is organized into two parts. Firstly, a collection of 'morphs' of solved
      structures representing different states of a molecule provides quantitative data
      for flexibility and a number of graphical representations. Secondly, a
      classification of known motions according to type of conformational change (e.g.
      'hinged domain' or 'allosteric') incorporates textual annotation and information
      from the literature relating to the motion, linking together many of the morphs.
      A variety of subsets of the morphs are being developed for use in statistical
      analyses. In particular, for each subset it is possible to derive distributions
      of various motional quantities (e.g. maximum rotation) that can be used to place
      a specific motion in context as being typical or atypical for a given population.
      Over the past year, the database has been greatly expanded and enhanced to
      incorporate new structures and to improve the quality of data. The 'morph
      server', which enables users of the database to add new morphs either from their
      own research or the PDB, has also been enhanced to handle nucleic acid structures
      and multi-chain complexes.

PMID- 12520057
TI  - NTDB: Thermodynamic Database for Nucleic Acids, Version 2.0.
AB  - The second release of Thermodynamic Database for Nucleic Acids, NTDB 2.0,
      includes more than 4600 entries (250% increase over release 1.0). It contains
      sequence types and details of several thermodynamic parameters (enthalpy, DeltaH;
      entropy, DeltaS; Gibbs free energy, DeltaG; melting temperature, T(m)),
      experimental models and methods for extracting thermodynamic parameters, buffer
      conditions as well as all relevant literature information. In addition, the
      database statistics and references related to NTDB are included. Information on
      normal and modified nucleobases and nucleosides are collected in a new section
      'Nucleoside' whereby data collected thus far will be release in NTDB 2.0. The
      NTDB is freely available at http://ntdb.chem.cuhk.edu.hk.

PMID- 12520058
TI  - Integration of related sequences with protein three-dimensional structural
      families in an updated version of PALI database.
AB  - The database of Phylogeny and ALIgnment of homologous protein structures (PALI)
      contains three-dimensional (3-D) structure-dependent sequence alignments as well
      as structure-based phylogenetic trees of protein domains in various families. The
      latest updated version (Release 2.1) comprises of 844 families of homologous
      proteins involving 3863 protein domain structures with each of these families
      having at least two members. Each member in a family has been structurally
      aligned with every other member in the same family using two proteins at a time.
      In addition, an alignment of multiple structures has also been performed using
      all the members in a family. Every family with at least three members is
      associated with two dendrograms, one based on a structural dissimilarity metric
      and the other based on similarity of topologically equivalenced residues for
      every pairwise alignment. Apart from these multi-member families, there are 817
      single member families in the updated version of PALI. A new feature in the
      current release of PALI is the integration, with 3-D structural families, of
      sequences of homologues from the sequence databases. Alignments between
      homologous proteins of known 3-D structure and those without an experimentally
      derived structure are also provided for every family in the enhanced version of
      PALI. The database with several web interfaced utilities can be accessed at:
      http://pauling.mbu.iisc.ernet.in/~pali.

PMID- 12520059
TI  - The Protein Data Bank and structural genomics.
AB  - The Protein Data Bank (PDB; http://www.pdb.org/) continues to be actively
      involved in various aspects of the informatics of structural genomics projects-
      developing and maintaining the Target Registration Database (TargetDB),
      organizing data dictionaries that will define the specification for the exchange
      and deposition of data with the structural genomics centers and creating software
      tools to capture data from standard structure determination applications.

PMID- 12520060
TI  - PDB-REPRDB: a database of representative protein chains from the Protein Data
      Bank (PDB) in 2003.
AB  - PDB-REPRDB is a database of representative protein chains from the Protein Data
      Bank (PDB). Started at the Real World Computing Partnership (RWCP) in August
      1997, it developed to the present system of PDB-REPRDB. In April 2001, the system
      was moved to the Computational Biology Research Center (CBRC), National Institute
      of Advanced Industrial Science and Technology (AIST) (http://www.cbrc.jp/); it is
      available at http://www.cbrc.jp/pdbreprdb/. The current database includes 33 368
      protein chains from 16 682 PDB entries (1 September, 2002), from which are
      excluded (a) DNA and RNA data, (b) theoretically modeled data, (c) short chains
      (1<40 residues), or (d) data with non-standard amino acid residues at all
      residues. The number of entries including membrane protein structures in the PDB
      has increased rapidly with determination of numbers of membrane protein
      structures because of improved X-ray crystallography, NMR, and electron
      microscopic experimental techniques. Since many protein structure studies must
      address globular and membrane proteins separately, this new elimination factor,
      which excludes membrane protein chains, is introduced in the PDB-REPRDB system.
      Moreover, the PDB-REPRDB system for membrane protein chains begins at the same
      URL. The current membrane database includes 551 protein chains, including
      membrane domains in the SCOP database of release 1.59 (15 May, 2002).

PMID- 12520061
TI  - The PSSH database of alignments between protein sequences and tertiary
      structures.
AB  - We introduce the PSSH ('Protein Sequence-to-Structure Homologies') database
      derived from HSSP2, an improved version of the HSSP ('Homology-derived Secondary
      Structure of Proteins') database [Dodge et al. (1998) Nucleic Acids Res., 26, 313
      315]. Whereas each HSSP entry lists all protein sequences related to a given 3D
      structure, PSSH is the 'inverse', with each entry listing all structures related
      to a given sequence. In addition, we introduce two other derived databases:
      HSSPchain, in which each entry lists all sequences related to a given PDB chain,
      and HSSPalign, in which each entry gives details of one sequence aligned onto one
      PDB chain. This re-organization makes it easier to navigate from sequence to
      structure, and to map sequence features onto 3D structures. Currently (September
      2002), PSSH provides structural information for over 400 000 protein sequences,
      covering 48% of SWALL and 61% of SWISS-PROT sequences; HSSPchain provides
      sequence information for over 25 000 PDB chains, and HSSPalign gives over 14
      million sequence-to-structure alignments. The databases can be accessed via SRS
      3D, an extension to the SRS system, at http://srs3d.ebi.ac.uk/.

PMID- 12520062
TI  - The RESID Database of Protein Modifications: 2003 developments.
AB  - The RESID Database is a comprehensive collection of annotations and structures
      for protein pre-, co- and post-translational modifications including amino
      terminal, carboxyl-terminal and peptide chain cross-link modifications. The RESID
      Database includes: systematic and alternate names, atomic formulas and masses,
      enzyme activities generating the modifications, keywords, literature citations,
      Gene Ontology cross-references, Protein Information Resource (PIR) and SWISS-PROT
      protein sequence database feature table annotations, structure diagrams and
      molecular models. This database is freely accessible on the Internet through the
      European Bioinformatics Institute at http://srs.ebi.ac.uk/srs6bin/cgi-bin/wgetz?
      page+LibInfo+-lib+RESID, through the National Cancer Institute - Frederick
      Advanced Biomedical Computing Center at http://www.ncifcrf.gov/RESID, or through
      the Protein Information Resource at
      http://pir.georgetown.edu/pirwww/dbinfo/resid.html.

PMID- 12520063
TI  - RNABase: an annotated database of RNA structures.
AB  - RNABase is a unified database of all three-dimensional structures containing RNA
      deposited in either the Protein Data Bank (PDB) or Nucleic Acid Data Base (NDB).
      For each structure, RNABase contains a brief summary as well as annotation of
      conformational parameters, identification of possible model errors, Ramachandran
      style conformational maps and classification of ribonucleotides into conformers.
      These same analyses can also be performed on structures submitted by users. To
      facilitate access, structures are automatically placed into a variety of
      functional and structural categories, including: ribozymes, pseudoknots, etc.
      RNABase can be freely accessed on the web at http://www.rnabase.org. We are
      committed to maintaining this database indefinitely.

PMID- 12520064
TI  - The Structure Superposition Database.
AB  - The need for new tools for investigating biological systems on a large scale is
      becoming acute, particularly with respect to computationally intensive analyses
      such as comparisons of many three-dimensional protein structures. Structure
      superposition is a valuable approach for understanding evolutionary relationships
      and for the prediction of function. But while available tools are adequate for
      generating and viewing superpositions of single pairs of protein structures,
      these tools are generally too cumbersome and time-consuming for examining
      multiple superpositions. To address this need, we have created the Structure
      Superposition Database (SSD) for accessing, viewing and understanding large sets
      of structure superposition data. The initial implementation of the SSD contains
      the results of pairwise, all-by-all superpositions of a representative set of 115
      (beta/alpha)8 barrel structures (TIM barrels). Future plans call for extending
      the database to include representative structure superpositions for many
      additional folds. The SSD can be browsed with a user interface module developed
      as an extension to Chimera, an extensible molecular modeling program. Features of
      the user interface module facilitate viewing multiple superpositions together.
      The SSD interface module can be downloaded from http://ssd.rbvi.ucsf.edu.

PMID- 12520065
TI  - GlycoSuiteDB: a curated relational database of glycoprotein glycan structures and
      their biological sources. 2003 update.
AB  - GlycoSuiteDB is an annotated and curated relational database of glycan structures
      reported in the literature. It contains information on the glycan type, core
      type, linkages and anomeric configurations, mass, composition and the analytical
      methods used by the researchers to determine the glycan structure. Native and
      recombinant sources are detailed, including species, tissue and/or cell type,
      cell line, strain, life stage, disease, and if known the protein to which the
      glycan structures are attached. There are links to SWISS-PROT/TrEMBL and PubMed
      where applicable. Recent developments include the implementation of searching by
      2D structure and substructure, disease and reference. The database is updated
      twice a year, and now contains over 7650 entries. Access to GlycoSuiteDB is
      available at http://www.glycosuite.com.

PMID- 12520066
TI  - probeBase: an online resource for rRNA-targeted oligonucleotide probes.
AB  - Ribosomal RNA-(rRNA)-targeted oligonucleotide probes are widely used for culture
      independent identification of microorganisms in environmental and clinical
      samples. ProbeBase is a comprehensive database containing more than 700 published
      rRNA-targeted oligonucleotide probe sequences (status August 2002) with
      supporting bibliographic and biological annotation that can be accessed through
      the internet at http://www.probebase.net. Each oligonucleotide probe entry
      contains information on target organisms, target molecule (small- or large
      subunit rRNA) and position, G+C content, predicted melting temperature, molecular
      weight, necessity of competitor probes, and the reference that originally
      described the oligonucleotide probe, including a link to the respective abstract
      at PubMed. In addition, probes successfully used for fluorescence in situ
      hybridization (FISH) are highlighted and the recommended hybridization conditions
      are listed. ProbeBase also offers difference alignments for 16S rRNA-targeted
      probes by using the probe match tool of the ARB software and the latest small
      subunit rRNA ARB database (release June 2002). The option to directly submit
      probe sequences to the probe match tool of the Ribosomal Database Project II (RDP
      II) further allows one to extract supplementary information on probe
      specificities. The two main features of probeBase, 'search probeBase' and 'find
      probe set', help researchers to find suitable, published oligonucleotide probes
      for microorganisms of interest or for rRNA gene sequences submitted by the user.
      Furthermore, the 'search target site' option provides guidance for the
      development of new FISH probes.

PMID- 12520069
TI  - The safety of genetically modified foods produced through biotechnology.

PMID- 12520070
TI  - Bile pigments: newcomers to the cell signaling arena.
AB  - The article highlighted in this issue is "2,3,7,8-Tetrachlorodibenzo-p-dioxin
      (TCDD)-Induced Accumulation of Biliverdin and Hepatic Peliosis in Rats," by Marjo
      Nittynen, Jouni T. Tuomisto, Seppo Auriola, Raimo Pohjanvirta, Paula Syrjala,
      Ulla Simanainen, Matti Viluksela, and Jouko Tuomisto (pp. 112-123).

PMID- 12520071
TI  - Real-time polymerase chain reaction analysis of CYP1B1 gene expression in human
      liver.
AB  - Procarcinogen-activating cytochrome P450 (CYP) enzymes such as CYP1B1, CYP1A1,
      and CYP1A2 are considered to play an important role in chemical carcinogenesis.
      However, conflicting data exist with respect to CYP1B1 expression in human liver.
      In the present study, we measured CYP1B1 mRNA and protein expression in liver
      samples from 12 individuals (7 nonsmokers, 4 smokers, and 1 ex-smoker) and
      compared the levels to those of CYP1A1 and CYP1A2. As analyzed by real-time
      polymerase chain reaction, CYP1B1 mRNA was present in all samples and the inter
      individual variability was 16-fold. The group mean level was 5-fold greater in
      smokers than nonsmokers (121 +/- 46 vs. 26 +/- 5 molecules/ng double-stranded
      DNA, p < 0.05). By comparison, CYP1A1 mRNA was detectable in samples from 4 of 7
      nonsmokers, 3 of 4 smokers, and one ex-smoker, whereas CYP1A2 mRNA was detectable
      in samples from 5 nonsmokers, 4 smokers, and the ex-smoker. The mean levels of
      CYP1A1 and CYP1A2 mRNA were 4-fold and 9-fold greater, respectively, in smokers
      than nonsmokers, but the differences were not statistically significant. The
      inter-individual variability in CYP1A1 and CYP1A2 mRNA expression was 26-fold and
      500-fold, respectively. Immunoblot analysis using several antibodies and with a
      larger panel (n = 27) of liver microsomes showed that CYP1A1 and CYP1B1 proteins
      were undetectable, whereas CYP1A2 was detectable in all samples and quantifiable
      in 24 of 27 samples. In summary, our novel finding indicates that CYP1B1 mRNA is
      expressed in human liver and the levels are increased in smokers, but the protein
      is undetectable.

PMID- 12520072
TI  - Correlation between gene expression of aryl hydrocarbon receptor (AhR),
      hydrocarbon receptor nuclear translocator (Arnt), cytochromes P4501A1 (CYP1A1)
      and 1B1 (CYP1B1), and inducibility of CYP1A1 and CYP1B1 in human lymphocytes.
AB  - The relationships between gene expression of aryl hydrocarbon receptor (AhR),
      aryl hydrocarbon receptor nuclear translocator (Arnt), cytochromes P4501A1
      (CYP1A1), 1B1 (CYP1B1), CYP1A1, and the inducibility of CYP1A1 and CYP1B1 were
      determined in 32 cultivated human lymphocytes. Cytochrome P450 induction was
      performed by incubating lymphocytes with benzanthracene. The relative gene
      expression levels were determined by quantitative real-time RT-PCR assay. We
      found that gender is an important confounding factor for gene expression in
      cultivated lymphocytes. AhR, CYP1A1 and CYP1B1 levels in noninduced lymphocytes
      were significantly higher in female nonsmokers than in male nonsmokers (p <
      0.05). Nevertheless, CYP1A1 and CYP1B1 inducibility was lower in female
      nonsmokers. CYP1A1 inducibility was higher in male smokers than in male
      nonsmokers (p < 0.05). After controlling for gender and cigarette smoking, AhR
      levels positively correlated with CYP1B1 levels and CYP1A1 inducibility (p < 0.01
      and p = 0.03, respectively). Arnt levels also correlated with CYP1B1 levels in
      induced lymphocytes (p < 0.01). However, AhR levels were negatively correlated
      with CYP1B1 inducibility. These data indicate that AhR expression associates with
      individual variation of CYP1A1 inducibility and CYP1B1 expression in cultivated
      lymphocytes. Furthermore, gender and cigarette smoking are important confounding
      factors for gene expression levels in cultivated lymphocytes.

PMID- 12520073
TI  - Physiologically based pharmacokinetic model parameter estimation and sensitivity
      and variability analyses for acrylonitrile disposition in humans.
AB  - A physiologically based pharmacokinetic (PBPK) model of acrylonitrile (ACN) and
      cyanoethylene oxide (CEO) disposition in humans was developed and is based on
      human in vitro data and scaling from a rat model (G. L. Kedderis et al., 1996,
      TOXICOL: Appl. Pharmacol.140, 422-435) for application to risk assessment. All of
      the major biotransformation and reactivity pathways, including metabolism of ACN
      to glutathione conjugates and CEO, reaction rates of ACN and CEO with glutathione
      and tissues, and the metabolism of CEO by hydrolysis and glutathione conjugation,
      were described in the human PBPK model. Model simulations indicated that
      predicted blood and brain ACN and CEO concentrations were similar in rats and
      humans exposed to ACN by inhalation. In contrast, rats consuming ACN in drinking
      water had higher predicted blood concentrations of ACN than humans exposed to the
      same concentration in water. Sensitivity and variability analyses were conducted
      on the model. While many parameters contributed to the estimated variability of
      the model predictions, the reaction rate of CEO with glutathione, hydrolysis rate
      for CEO, and blood:brain partition coefficient of CEO were the parameters
      predicted to make the greatest contributions to variability of blood and brain
      CEO concentrations in humans. The main contributor to predicted variance in human
      blood ACN concentrations in people exposed through drinking water was the Vmax
      for conversion of ACN to CEO. In contrast, the main contributors for variance in
      people exposed by inhalation were expected to be the rate of blood flow to the
      liver and alveolar ventilation rate, with the brain:blood partition coefficient
      also contributing to variability in predicted concentrations of ACN in the brain.
      Expected variability in blood CEO concentrations (peak or average) in humans
      exposed by inhalation or drinking water was modest, with a 95th-percentile
      individual expected to have blood concentrations 1.8-times higher than an average
      individual.

PMID- 12520074
TI  - Route-specific differences in distribution characteristics of
      octamethylcyclotetrasiloxane in rats: analysis using PBPK models.
AB  - Octamethylcyclotetrasiloxane (D(4)) is used in selected consumer products and has
      a potential for human exposure from multiple routes. Here we develop a
      physiologically based pharmacokinetic (PBPK) model to describe the tissue
      dosimetry, plasma concentration, and clearance in the rat following inhalation
      and dermal, oral, and iv exposure. An initial multiroute PBPK model, based on a
      previously published inhalation PBPK model for D(4), provided excellent fits to
      the observed concentration time course of D(4) metabolites in urine and D(4)
      exhalation rate following dermal exposures. However, the pharmacokinetics of
      D(4), following oral and iv exposure, were sensitive to the mode of entry into
      the blood compartment. A refined model, describing delivery of D(4) from the GI
      tract to the nonexchangeable/deep blood compartment, provided the best fits to
      observed plasma D(4), exhaled D(4), and D(4) metabolites excreted in the urine
      following oral exposure. Pharmacokinetics following iv administration was best
      described by delivery of D(4) directly into the deep blood compartment, possibly
      reflecting a kinetically identifiable characteristic of the administration of
      D(4) as an emulsion for the intravenous route of exposure. This model-based
      analysis indicates that the pharmacokinetics of D(4) delivered by the inhalation
      or dermal routes is similar, and is different from the iv or oral delivery
      routes.

PMID- 12520075
TI  - Evaluation of potential modes of action of inhaled ethylbenzene in rats and mice.
AB  - Potential factors underlying the tumorigenic activity of ethylbenzene (EB) were
      examined in F344 rats and B6C3F1 mice inhaling 750 ppm EB vapor 6 h/day, 5
      days/week, for one or four weeks. Target tissues (kidneys of rats and livers and
      lungs of mice) were evaluated for changes in organ weights, mixed function
      oxygenases (MFO), glucuronosyl transferase activities, S-phase DNA synthesis,
      apoptosis, alpha2u-globulin deposition, and histopathology. In male rats, kidney
      weight increases were accompanied by focal increases in hyaline droplets, alpha2u
      globulin, degeneration, and S-phase synthesis in proximal tubules. In female
      rats, only decreased S-phase synthesis and MFO activities occurred. In mice,
      increased liver weights were accompanied by hepatocellular hypertrophy, mitotic
      figures, S-phase synthesis, and enzyme activities. S-phase synthesis rates in
      terminal bronchiolar epithelium were elevated and accompanied by loss of MFO
      activity. Exposure to a nontumorigenic level of 75 ppm for one week caused few
      changes. These data, considered with the general lack of EB genotoxicity, suggest
      a mode of tumorigenesis dependent upon increased cell proliferation and altered
      population dynamics in male rat kidney and mouse liver and lungs. A similar
      response in the kidneys of female rats appears to require a longer exposure
      period than was employed.

PMID- 12520076
TI  - Metabolism of chrysene by brown bullhead liver microsomes.
AB  - We have investigated the regio- and stereoselective metabolism of chrysene, a
      four-ring symmetrical carcinogenic polycyclic aromatic hydrocarbon (PAH), by the
      liver microsomes of brown bullhead (Ameriurus nebulosus), a bottom-dwelling fish
      species. The liver microsomes from untreated and 3-methylcholanthrene (3-MC)
      treated brown bullheads metabolized chrysene at the rate of 30.1 and 82.2 pmol/mg
      protein/min, respectively. Benzo-ring diols (1,2-diol and 3,4-diol) were the
      major chrysene metabolites formed by liver microsomes from control and 3-MC
      treated fish. However, the control microsomes produced a considerably higher
      proportion of chrysene 1,2-diol (benzo-ring diol with a bay region double bond)
      plus 1-hydroxychrysene, than 3,4-diol plus 3-hydroxychrysene, indicating that
      these microsomes are selective in attacking the 1,2- position of the benzo-ring.
      On the other hand, 3-MC-induced microsomes did not show such a regioselectivity
      in the metabolism of chrysene. Control bullhead liver microsomes, compared to
      control rat liver microsomes, produced a considerably higher proportion of
      chrysene 1,2-diol, the putative proximate carcinogenic metabolite of chrysene.
      Like rat liver microsomes, bullhead liver microsomes produced only trace amounts
      of the K-region diol. Chrysene 1,2-diol and 3,4-diol formed by the liver
      microsomes from both control and 3-MC-treated bullheads consisted predominantly
      of their R,R-enantiomers. Chrysene is metabolized by bullhead liver microsomal
      enzymes to its benzo-ring diols with a relatively lower degree of
      stereoselectivity compared to benzo[a]pyrene (a five-ring PAH), but with a higher
      degree of stereoselectivity compared to phenanthrene (a three-ring PAH). The data
      of this study, together with those from our previous studies with phenanthrene,
      benzo[a]pyrene and dibenzo[a,l]pyrene (a six-ring PAH), indicate that the
      regioselectivity in the metabolism of PAHs by brown bullhead and rainbow trout
      liver microsomes does not vary greatly with the size and shape of the molecule,
      whereas the degree of stereoselectivity in the metabolism of PAHs to benzo-ring
      dihydrodiols does.

PMID- 12520077
TI  - The effects of the phytoestrogen genistein on the postnatal development of the
      rat.
AB  - The present studies report the effects on neonatal rats of oral exposure to
      genistein during the period from birth to postnatal day (PND) 21 to generate data
      for use in assessing human risk following oral ingestion of genistein. Failure to
      demonstrate significant exposure of the newborn pups via the mothers milk led us
      to subcutaneously inject genistein into the pups over the period PND 1-7,
      followed by daily gavage dosing to PND 21. The targeted doses throughout were 4
      mg/kg/day genistein (equivalent to the average exposure of infants to total
      isoflavones in soy milk) and a dose 10 times higher than this (40 mg/kg
      genistein). The dose used during the injection phase of the experiment was based
      on plasma determinations of genistein and its major metabolites.
      Diethylstilbestrol (DES) at 10 micro g/kg was used as a positive control agent
      for assessment of changes in the sexually dimorphic nucleus of the preoptic area
      (SDN-POA). Administration of 40 mg/kg genistein increased uterus weights at day
      22, advanced the mean day of vaginal opening, and induced permanent estrus in the
      developing female pups. Progesterone concentrations were also decreased in the
      mature females. There were no effects in females dosed with 4 mg/kg genistein,
      the predicted exposure level for infants drinking soy-based infant formulas.
      There were no consistent effects on male offspring at either dose level of
      genistein. Although genistein is estrogenic at 40 mg/kg/day, as illustrated by
      the effects described above, this dose does not have the same repercussions as
      DES in terms of the organizational effects on the SDN-POA.

PMID- 12520078
TI  - EGF and TGF-alpha expression influence the developmental toxicity of TCDD: dose
      response and AhR phenotype in EGF, TGF-alpha, and EGF + TGF-alpha knockout mice.
AB  - The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces
      cleft palate (CP) and hydronephrosis (HN) in mice. The etiology of these defects
      involves hyperproliferation of epithelial cells of the secondary palatal shelf
      and ureter, respectively. These effects correlate with altered expression of the
      epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), and
      transforming growth factor-alpha (TGF-alpha). In this study, the developmental
      toxicity of TCDD was examined in EGF, TGF-alpha, and double EGF + TGF-alpha
      knockout (-/-) and wild type (WT) mice. The influence of background genetics in
      responsiveness to TCDD was examined using liver 7-ethoxyresorufin-O-deethylase
      (EROD) activity. Animals were dosed by gavage with 0, 0.2, 1, 5, 24, 50, 100, or
      150 micro g TCDD/kg (5 ml/kg) body weight on gestation day 12. The mixed genetic
      background of WT, EGF (-/-), and EGF + TGF-alpha (-/-) made these mice less
      responsive to TCDD relative to C57BL/6J and TGF-alpha (-/-), which have a C57BL
      background. These results show that EGF and TGF-alpha are not required for
      response to TCDD; however, the specific ligand available to bind EGFR affects the
      responsiveness to TCDD. EGF (-/-) mice are less responsive for CP, but more
      sensitive to HN. TGF-alpha (-/-) mice were similar to WT in sensitivity for
      induction of CP and HN. The responses of EGF + TGF-alpha (-/-) mice were like the
      WT except at higher doses where sensitivity to CP increased, suggesting that the
      responses may be mediated by alternative ligands for EGFR that are not functional
      equivalents of EGF or TGF-alpha. In conclusion, the EGFR pathway is
      mechanistically important in responses of the embryo to TCDD. Specific ligands
      confer sensitivity or resistance that are target tissue-dependent.

PMID- 12520079
TI  - Exposure to 1-bromopropane causes ovarian dysfunction in rats.
AB  - Although 1-bromopropane has been used in chemical and electronic industries as an
      alternative to ozone layer-depleting solvents, its toxicity on female
      reproductive organs has not been fully elucidated. The aim of this experiment was
      to determine the effect of 1-bromopropane on female reproductive function in
      rats. Forty female Wistar rats were divided into four equal groups. Each group
      was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day.
      After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill
      and were sacrificed during the 8th week. The other dose groups were exposed for
      12 weeks. In the 800-ppm group, but not in the other two exposed groups, body
      weight was significantly less than the control at each time point from 2 to 7
      weeks after the beginning of exposure. Tests of vaginal smears showed a
      significant increase in the number of irregular estrous cycles with extended
      diestrus in the 400- and 800-ppm groups. Histopathological examination of the
      ovary showed a significant dose-dependent reduction of the number of normal
      antral follicles and a decrease in the number of normal growing follicles in the
      400-ppm group. No significant change was found in plasma concentrations of LH or
      FSH in any group when compared with the control. Our results indicate that 1
      bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant
      female rats associated with disruption in follicular growth process.

PMID- 12520080
TI  - Respiratory deposition and inhalability of monodisperse aerosols in Long-Evans
      rats.
AB  - Because of limitations on conducting exposure experiments using human subjects to
      evaluate adverse health effects, the deposition and fate of airborne particles in
      animals are often studied. The results of such studies are extrapolated to humans
      to estimate equivalent dose and subsequent response. In this article, particle
      inhalability and respiratory deposition of micron-size particles are determined
      for female Long-Evans rats. Monodisperse aerosols were generated from a solution
      of radiolabeled iron chloride ((59)FeCl(3)). Long-Evans rats were exposed to the
      radiolabeled particles in a Cannon nose-only exposure tower to determine head,
      lung lobar, and total lung deposition fractions. Particle deposition fractions in
      a hypothetical situation, when all particles are inhalable, were found from an
      experimentally validated deposition model. Particle inhalability in a Cannon nose
      only exposure scenario was obtained by comparing the measured deposition
      fractions with the predicted values for the case of 100% inhalability. Particle
      deposition fraction and inhalability were compared with data available in the
      literature. For large particles, the measured deposition fraction was lower than
      the literature values. Consequently, our inhalability estimates were found to be
      lower than previously published values. The findings here will directly affect
      health risk assessments in humans from exposure to airborne particles. The
      deposition results will improve the database on particle deposition in the lung
      airways of rats, and inhalability information will improve the accuracy of rat-to
      human data extrapolation.

PMID- 12520081
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced accumulation of biliverdin and
      hepatic peliosis in rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread, persistent, and
      highly toxic environmental pollutant. The most TCDD-sensitive and the most TCDD
      resistant rat strains (Long-Evans [Turku/AB] and Han/Wistar [Kuopio],
      respectively) were crossbred to separate the alleles of two genes (Ahrand an
      unidentified gene "B") mediating resistance against TCDD toxicity. During
      crossbreeding, a new type of toxicity in livers of both sexes was detected,
      characterized macroscopically by intense dark green to black color and swelling
      that appeared most frequently after a large dose (300 micro g/kg or more as a
      single intragastric dose) and a follow-up period of more than three weeks.
      Therefore, studies were undertaken to identify the causative pigment chemically
      and to examine the hepatotoxicity histologically. The pigment fractions were
      separated by thin layer chromatography and then analyzed by HPLC and electrospray
      mass spectrometry. The pigment was found to consist of biliverdin and several
      biliverdin-related compounds. In liver histopathology carried out on male rats,
      progressive sinusoidal distension and hepatic peliosis with membrane-bound cysts
      were seen. The clinical manifestations of pigment accumulation were recorded most
      often in intermediately resistant rat lines such as line B (homozygous for the
      gene B), but never occurred in rats expressing only the Han/Wistar (Kuopio)-type
      Ah receptor with an altered transactivation domain structure.

PMID- 12520082
TI  - The role of Kupffer cells and TNF-alpha in monocrotaline and bacterial
      lipopolysaccharide-induced liver injury.
AB  - Coexposure to small, noninjurious doses of the pyrrolizidine alkaloid phytotoxin
      monocrotaline (MCT) and bacterial lipopolysaccharide (LPS) results in synergistic
      hepatotoxicity. Both centrilobular and midzonal liver lesions occur and are
      similar to those seen from large, toxic doses of MCT and LPS, respectively. The
      nature of the lesions in vivo and results from studies in vitro suggest that
      injury is mediated indirectly rather than from a simple interaction of MCT and
      LPS with hepatic parenchymal cells. Accordingly, the role of inflammatory
      factors, such as Kupffer cells and TNF-alpha, in the development of MCT/LPS
      induced liver injury was investigated. In Sprague-Dawley rats, MCT (100 mg/kg,
      i.p.) was administered 4 h before LPS (7.4 x 10(6) EU/kg, i.v.). Pretreatment of
      these animals with gadolinium chloride, an inhibitor of Kupffer cell function,
      attenuated liver injury 18 h after MCT administration. An increase in plasma TNF
      alpha preceded the onset of hepatic parenchymal cell injury, raising the
      possibility that this inflammatory cytokine contributes to toxicity. Either
      pentoxifylline, an inhibitor of cellular TNF-alpha synthesis, or anti-TNF-alpha
      serum coadministered to MCT/LPS-treated animals significantly attenuated liver
      injury. These results suggest that Kupffer cells and TNF-alpha are important
      mediators in the synergistic hepatotoxicity resulting from MCT and LPS
      coexposure.

PMID- 12520083
TI  - Molecular evidence-based use of bone resorption-targeted therapy in prostate
      cancer patients at high risk for bone involvement.
AB  - BACKGROUND: To improve median survival of patients with prostate cancer that has
      metastasized to bone, we need to better understand the early events of the
      metastatic process in skeleton and develop molecular tools capable of detecting
      the early tumor cell dissemination into bones (micrometastasis stage). However,
      the initial phase of tumor cell dissemination into the bone marrow is promptly
      followed by the migration of tumor cells into bone matrix, which is a crucial
      step that signals the transformation of micrometastasis to macrometastasis stage
      and clinically evident metastasis. The migration of cancer cells into bone matrix
      requires the activation of local bone resorption. Such an event contributes to
      tumor cell hiding/ escaping from high immunologic surveillance of bone marrow
      cells. Within bone matrix, tumor cells are establishing plethoric cell-cell
      interactions with bone marrow-residing cells, ensuring their survival and growth.
      Recently, RT-PCR detections of tumor marker transcripts, such as PSA and PSMA
      mRNA performed in RNA extracts of peripheral blood nucleated cells and bone
      marrow biopsy, have enabled the stratification of patients with clinically
      localized prostate cancer being of high risk for extraprostatic disease and bone
      involvement. Therefore, it is conceivable that bisphosphonate blockade of bone
      resorption can inhibit the migration of tumor cells into bone matrix during the
      early phase of disease dissemination into bone marrow (micrometastasis stage).
      Consequently, assessment of the efficacy and efficiency of bisphosphonates to
      arrest the evolution of bone lesions in this particular clinical setting of
      patients with clinically localized prostate cancer and positive molecular staging
      status (high risk for bone involvement) is warranted.

PMID- 12520085
TI  - Involvement of [beta]-glucans in the wide-spectrum antimicrobial activity of
      Williopsis saturnus var. mrakii MUCL 41968 killer toxin.
AB  - BACKGROUND: Williopsis saturnus var. mrakii MUCL 41968 secretes a 85-kDa
      glycoprotein killer toxin (WmKT) that displays a cytocidal activity against a
      wide range of microorganisms, making WmKT a promising candidate for the
      development of new antimicrobial molecules. Although the killing mechanism of
      WmKT is still unknown, the toxin was recently proposed to bind to the surface of
      sensitive microorganisms through the recognition of beta-glucans. Indeed,
      Saccharomyces cerevisiae strains sensitive to the toxin become resistant when
      mutated in their beta-glucan synthesis pathway. MATERIALS AND METHODS: To
      investigate the interaction of WmKT with beta-glucans, we examined in agar
      diffusion assays the WmKT activity in the presence of enzymes displaying beta
      glucanase activity. The toxin activity was also investigated using spheroplasts
      derived from sensitive yeast cells. The hydrolytic activity of WmKT was studied
      using specific glucosidase inhibitors as well as various sugar molecules
      covalently linked to p-nitrophenyl as potential substrates. Finally, the
      ultrastructural modifications induced by WmKT activity on sensitive yeasts were
      assessed by scanning electron microscopy. RESULTS: The data reported here support
      the hypothesis that WmKT binds to sensitive cells using surface-exposed beta
      glucans. Indeed beta-glucanase exerts an antagonistic effect on WmKT activity and
      spheroplasts derived from WmKT-sensitive yeast cells are shown to be resistant to
      WmKT, suggesting that cell wall beta-glucans are required for WmKT lethal effect.
      Because WmKT exhibits amino acid sequence similarities with proteins suspected to
      be glucanase, we also investigated the effect of castanospermine, a potent
      glucosidase inhibitor, on WmKT activity. Castanospermine completely abolished
      WmKT killer activity as well as its hydrolytic enzymatic activity against p
      nitrophenyl beta-D-glucopyranoside. The scanning electron microscopy analysis of
      sensitive yeast cells treated with the toxin reveals that WmKT causes cell wall
      modifications similar to those observed with zymolyase. CONCLUSION: The results
      reported in this study show that WmKT activity requires an interaction between
      the mycocin and the cell wall beta-glucans. Moreover, they indicate that WmKT
      acts on sensitive yeast cells through a hydrolytic activity directed against cell
      wall beta-glucans that disrupts the yeast cell wall integrity leading to death.

PMID- 12520084
TI  - HIV-1 gp120-induced tubular epithelial cell apoptosis is mediated through p38
      MAPK phosphorylation.
AB  - BACKGROUND: HIV-associated nephropathy is accompanied by significant tubular
      alterations in the form of tubular cell proliferation, apoptosis, and microcystic
      dilatation. In the present study we evaluated the role of CD4 receptors in HIV-1
      induced tubular cell injury. METHODS: To confirm the presence of CD4 receptors in
      tubular cells, immunocytochemical, Western and Northern blot studies were carried
      out. To determine the downstream effect of CD4 and gp120 interaction, we
      evaluated the effect of gp120 on tubular cell p38 mitogen-activated protein
      kinase (MAPK) activity and phosphorylation. To establish causal relationships
      between gp120, CD4, and p38 MAPK pathways, we studied the effect of anti-CD4
      antibody and SB 202190 (an inhibitor of p38 MAPK) on gp120-induced tubular cell
      apoptosis. RESULTS: Proximal tubular cells in culture as well as in intact tissue
      showed expression of CD4 (immunocytochemical and Western blot studies). Cultured
      tubular cells also showed mRNA expression for CD4 (Northern blot studies). Gp120,
      at concentrations of 10-100 ng/ ml, triggered tubular cell apoptosis; however,
      this effect of gp120 was inhibited by anti-CD4 antibody. SB 202190 also inhibited
      gp120-induced tubular cell apoptosis. In addition, gp120 promoted tubular cell
      p38 MAPK phosphorylation in a time- and dose- dependent manner. CONCLUSION: Gp120
      through interaction with CD4 triggers tubular cell apoptosis. This effect of
      gp120 on tubular cells is mediated through phosphorylation of p38 MAPK.

PMID- 12520086
TI  - Overexpression of the Shb SH2 domain-protein in insulin-producing cells leads to
      altered signaling through the IRS-1 and IRS-2 proteins.
AB  - BACKGROUND: Overexpression of the Src homology 2 domain protein Shb in beta-cells
      of transgenic mice has been shown to promote an increased beta-cell mass. To
      investigate the mechanisms by which Shb controls the beta-cell mass, we have
      presently studied the effects of Shb overexpression on the IRS-1-induced
      signaling pathway in mouse islet beta-cells and in insulin-producing RINm5F cells
      and correlated these effects to growth and death patterns. MATERIALS AND METHODS:
      Shb overexpression was achieved in RINm5F cells by selection of stable clones or
      by FACS purification of transiently transfected cells. For Shb overexpression in
      primary mouse islet cells, a Shb-transgene mouse was used. Cell proliferation and
      death rates were determined using flow cytometry. Serum-, insulin-, and IGF-1
      stimulated signaling events were studied by immunoblot, immunoprecipitation, and
      in vitro kinase procedures. RESULTS: Transient Shb overexpression in RINm5F cells
      resulted in increased proliferation. Both Shb-overexpressing RINm5F cells and
      islet cells from transgenic mice (islet Shb) exhibited increased basal tyrosine
      phosphorylation of IRS-1. Shb overexpression resulted also in the assembly and
      activation of a multiunit complex consisting of at least Shb, IRS-1, IRS-2, FAK,
      and PI3K. Consequently, the phosphorylation of Akt was enhanced under basal
      conditions in Shb overexpressing cells. Finally, Shb overexpression did not
      affect insulin-induced phosphorylation of the PI3K-antagonist PTEN. CONCLUSION:
      It is concluded that the Shb-induced alterations in the IRS-1/PI3K/Akt pathway
      may be relevant to the understanding of growth and death patterns of insulin
      producing cells.

PMID- 12520088
TI  - The multidrug transporters belonging to major facilitator superfamily in
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Both intrinsic and acquired multidrug resistance play an important
      role in the insurgence of tuberculosis. Detailed knowledge of the molecular basis
      of drug recognition and transport by multidrug transport systems is required for
      the development of new antibiotics that are not extruded or of inhibitors that
      block the multidrug transporter and allow traditional antibiotics to be
      effective. MATERIALS AND METHODS: We have undertaken the inventory of the drug
      transporters subfamily, included in the major facilitator superfamily (MFS),
      encoded by the complete genome of Mycobacterium tuberculosis (MTB). These
      proteins were identified on the basis of their characteristic stretches of amino
      acids and transmembrane segments (TMS) number. CONCLUSIONS: Genome analysis and
      searches of homology between the identified transporters and proteins
      characterized in other organisms revealed 16 open reading frames encoding
      putative drug efflux pumps belonging to MFS. In the case of two of them, we also
      have demonstrated that they function as drug efflux proteins.

PMID- 12520087
TI  - GTK tyrosine kinase-induced alteration of IRS-protein signalling in insulin
      producing cells.
AB  - BACKGROUND: Insulin receptor substrate proteins (IRS) mediate various effects of
      insulin, including regulation of glucose homeostasis, cell growth and survival.
      To understand the underlying mechanisms explaining the effects of the Src-related
      tyrosine kinase GTK on beta-cell proliferation and survival, insulin-signalling
      pathways involving IRS-1 and IRS-2 were studied in islet cells and RINm5F cells
      overexpressing wild-type and two different mutants of the SRC-related tyrosine
      kinase GTK. MATERIALS AND METHODS: Islets isolated from transgenic mice and
      RINm5F cells overexpressing wild-type and mutant GTK were analysed for IRS-1, IRS
      2, SHB, AKT and ERK phosphorylation/activity by Western blot analysis. RESULTS:
      RINm5F cells expressing the kinase active mutant Y504F-GTK and islet cells from
      GTK(Y504F) -transgenic mice exhibited reduced insulin-induced tyrosine
      phosphorylation of IRS-1 and IRS-2. In RINm5F cells, the diminished IRS
      phosphorylation was accompanied by a reduced insulin-stimulated activation of
      phosphatidylinositol 3-kinase (PI3K), AKT and Extracellular Signal-Regulated
      Kinase, partly due to an increased basal activity. In addition, increased
      tyrosine phosphorylation of the SHB SH2 domain-adaptor protein and its
      association with IRS-2, IRS-1 and focal adhesion kinase was observed in these
      cells. RINm5F cells overexpressing wild-type GTK also exhibited reduced
      activation of IRS-2, PI3K and AKT, whereas cells expressing a GTK mutant with
      lower kinase activity (GTK(Y394F)) exhibited insignificantly altered responses to
      insulin compared to the mock transfected cells. Moreover, GTK was shown to
      associate with and phosphorylate SHB in transiently transfected COS-7 cells,
      indicating that SHB is a specific substrate for GTK. CONCLUSIONS: The results
      suggest that GTK signals via SHB to modulate insulin-stimulated pathways in beta
      cells and this may explain previous results showing an increased beta-cell mass
      in GTK-transgenic mice.

PMID- 12520089
TI  - Selective inhibition of FLICE-like inhibitory protein expression with small
      interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL
      induced apoptosis.
AB  - BACKGROUND: Most tumors express death receptors and their activation represents a
      potential selective approach in cancer treatment. The most promising candidate
      for tumor selective death receptor-activation is tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)/Apo2L, which activates the death receptors
      TRAIL-R1 and TRAIL-R2, and induces apoptosis preferentially in tumor cells but
      not in normal tissues. However, many cancer cells are not or only moderately
      sensitive towards TRAIL and require cotreatment with irradiation or chemotherapy
      to yield a therapeutically reasonable apoptotic response. Because chemotherapy
      can have a broad range of unwanted side effects, more specific means for
      sensitizing tumor cells for TRAIL are desirable. The expression of the cellular
      FLICE-like inhibitory protein (cFLIP) is regarded as a major cause of TRAIL
      resistance. We therefore analyzed the usefulness of targeting FLIP to sensitize
      tumor cells for TRAIL-induced apoptosis. MATERIALS AND METHODS: To selectively
      interfere with expression of cFLIP short double-stranded RNA oligonucleotides
      (small interfering RNAs [siRNAs]) were introduced in the human cell lines SV80
      and KB by electroporation. Effects of siRNA on FLIP expression were analyzed by
      Western blotting and RNase protection assay and correlated with TRAIL sensitivity
      upon stimulation with recombinant soluble TRAIL and TRAIL-R1- and TRAIL-R2
      specific agonistic antibodies. RESULTS: FLIP expression can be inhibited by RNA
      interference using siRNAs, evident from reduced levels of FLIP-mRNA and FLIP
      protein. Inhibition of cFLIP expression sensitizes cells for apoptosis induction
      by TRAIL and other death ligands. In accordance with the presumed function of
      FLIP as an inhibitor of death receptor-induced caspase-8 activation, down
      regulation of FLIP by siRNAs enhanced TRAIL-induced caspase-8 activation.
      CONCLUSION: Inhibition of FLIP expression was sufficient to sensitize tumor cells
      for TRAIL-induced apoptosis. The combination of TRAIL and FLIP-targeting siRNA
      could therefore be a useful strategy to attack cancer cells, which are resistant
      to TRAIL alone.

PMID- 12520090
TI  - Adenoviral-induced islet cell cytotoxicity is not counteracted by Bcl-2
      overexpression.
AB  - BACKGROUND: The ability to transfer immunoregulatory, cytoprotective, or anti
      apoptotic genes into pancreatic islet cells may allow enhanced resistance against
      the autoimmune destruction of these cells in type 1 diabetes. We describe here an
      inducible transduction system for expression of the anti-apoptotic bcl-2 gene in
      insulin-producing cells as a potential tool for protecting against beta-cell
      death. MATERIALS AND METHODS: Isolated pancreatic rat islet cells or rat
      insulinoma (RINm5F) cells were transduced using a progesterone antagonist (RU
      486) inducible adenoviral vector system, expressing the bcl-2 gene. Bcl-2
      overexpression was measured by Western blot assays and flow cytometry analysis.
      Following exposure to cytokines or to the mitochondrial uncoupler FCCP, cell
      survival was determined using fluorescence and electron microscopy, and a
      colorimetric assay (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]- 2H-tetrazolium-5
      carboxanilide [XTT]-based) for cell viability. The mitochondrial membrane
      potential ((m)) was assessed using the lipophilic cationic membrane potential
      sensitive dye JC-1. RESULTS: The adenoviral gene transfer system induced Bcl-2
      expression in more than 70% of beta-cells and the protein expression levels were
      successfully regulated in response to varying concentrations of progesterone
      antagonist RU 486. Exposure of islet cells to proinflammatory cytokines IL-1beta,
      TNF-alpha, and IFN-gamma, or to the mitochondrial uncoupler FCCP resulted in
      disruption of the mitochondrial membrane potential ((m)) and beta-cell death. Bcl
      2 overexpression stabilized (m) and prevented cell death in RINm5F cells but not
      in islet cells. In addition, prolonged in vitro culture revealed adenoviral
      induced islet cell necrosis. CONCLUSIONS: The RU 486-regulated adenoviral system
      can achieve an efficient control of gene transfer at relatively low doses of the
      adenoviral vector. However, Bcl-2 overexpression in islet cells did not prevent
      adenoviral- or cytokine-induced toxicity, suggesting that the specific death
      pathway involved in adenoviral toxicity in beta-cells may bypass the
      mitochondrial permeability transition event.

PMID- 12520091
TI  - Early exposure to genistein exerts long-lasting effects on the endocrine and
      immune systems in rats.
AB  - BACKGROUND: Although the immunologic effects of endogenous and synthetic
      estrogens are well studied, few studies have examined the hormonal effects of
      phytoestrogens (i.e., plant-derived estrogens) on the immune system. The primary
      goal of this study was to compare the effects of perinatal exposure with life
      long exposure to genistein, an estrogenic compound in soy, on the endocrine and
      immune system in adulthood. MATERIALS AND METHODS: Pregnant female rats were
      exposed to no, low (5 mg/kg diet), or high (300 mg/kg diet) genistein diets
      throughout gestation and lactation. At weaning, male offspring exposed to
      genistein perinatally were either switched to the genistein-free diet or remained
      on the genistein-dosed diets. At 70 days of age, immune organ masses, lymphocyte
      subpopulations, cytokine concentrations, and testosterone concentrations were
      assessed in male offspring. RESULTS: Data were analyzed based on the diets that
      males were exposed to during gestation and lactation because life-long exposure
      to genistein had no additional effect on any of the dependent measures. Relative
      thymus masses were greater among males exposed to the high genistein diet than
      among males exposed to no genistein. Although the proportions of splenic and
      thymic CD4+ T cells were not altered by genistein, the percentages of CD4+CD8+
      thymocytes, CD8+ splenocytes, and total T cells in the spleen were higher and the
      percentages of CD4-CD8- thymocytes were lower among males exposed to genistein
      than among males not exposed to genistein. Synthesis of interferon-gamma (IFN
      gamma) was marginally higher and testosterone concentrations were lower among
      genistein-exposed than genistein-free males. DISCUSSION: These data illustrate
      that exposure to genistein during pregnancy and lactation exerts long-lasting
      effects on the endocrine and immune systems in adulthood. Whether exposure to
      phytoestrogens during early development affects responses to infectious or
      autoimmune diseases, as well as cancers, later in life requires investigation.

PMID- 12520093
TI  - The urodele egg-coat as the apparatus adapted for the internal fertilization.
AB  - Fertilization is a significant event for reproducing offspring. It is achieved
      under a species-specific environment, which influences the conditions to assure
      the successful fertilization in some cases. Several studies about the basic
      mechanism of fertilization suggest that the fertilization mechanism is modified
      among species to be suited for the fertilization environment. In amphibians, many
      anurans undergo external fertilization while most urodeles do internal
      fertilization. An amphibian egg is surrounded by egg-coats, which are composed of
      vitelline envelope and layered egg-jelly. They are significant as fields for the
      sperm-egg interaction at fertilization. The fertilization processes that take
      place in the egg-coats are supposed to be easily influenced by the fertilization
      environment, because they, especially egg-jelly, are exposed to the surroundings
      at fertilization. In the present article, we describe the fertilization system
      equipped in newt egg-coats. Newt sperm are stored in spermatheca that exists in
      cloaca of a female and directly inseminated on the surface of egg-jelly. Sperm
      motility and acrosome reaction are induced in the outermost portion of the egg
      jelly. Motion of the moving sperm becomes vigorous in the egg-jelly and sperm are
      guided to vitelline envelope by the aid of egg-jelly structure. Most of the sperm
      passing through the egg-jelly, as the result, has been induced acrosome reaction
      and those sperm can bind to the vitelline envelope to contribute to the
      successful fertilization. This fertilization system has a distinct feature from
      the known system in species undergoing external fertilization. The feature of the
      system in the newt egg-jelly is discussed with the view to achieving the
      successful fertilization in the internal environment.

PMID- 12520092
TI  - Coordinate changes in Myosin heavy chain isoform gene expression are selectively
      associated with alterations in dilated cardiomyopathy phenotype.
AB  - BACKGROUND: The most common cause of chronic heart failure in the US is secondary
      or primary dilated cardiomyopathy (DCM). The DCM phenotype exhibits changes in
      the expression of genes that regulate contractile function and pathologic
      hypertrophy. However, it is unclear if any of these alterations in gene
      expression are disease producing or modifying. MATERIALS AND METHODS: One
      approach to providing evidence for cause-effect of a disease-influencing gene is
      to quantitatively compare changes in phenotype to changes in gene expression by
      employing serial measurements in a longitudinal experimental design. We
      investigated the quantitative relationships between changes in gene expression
      and phenotype n 47 patients with idiopathic DCM. In endomyocardial biopsies at
      baseline and 6 months later, we measured mRNA expression of genes regulating
      contractile function (beta-adrenergic receptors, sarcoplasmic reticulum Ca(2) +
      ATPase, and alpha- and beta-myosin heavy chain isoforms) or associated with
      pathologic hypertrophy (beta-myosin heavy chain and atrial natriuretic peptide),
      plus beta-adrenergic receptor protein expression. Left ventricular phenotype was
      assessed by radionuclide ejection fraction. RESULTS: Improvement in DCM phenotype
      was directly related to a coordinate increase in alpha- and a decrease in beta
      myosin heavy chain mRNA expression. In contrast, modification of phenotype was
      unrelated to changes in the expression of beta(1)- or beta(2)-adrenergic receptor
      mRNA or protein, or to the mRNA expression of sarcoplasmic reticulum Ca(2) +
      ATPase and atrial natriuretic peptide. CONCLUSION: We conclude that in human DCM,
      phenotypic modification is selectively associated with myosin heavy chain isoform
      changes. These data support the hypothesis that myosin heavy chain isoform
      changes contribute to disease progression in human DCM.

PMID- 12520094
TI  - Fluorescent in situ hybridisation to amphioxus chromosomes.
AB  - We describe an efficient protocol for mapping genes and other DNA sequences to
      amphioxus chromosomes using fluorescent in situ hybridisation. We apply this
      method to identify the number and location of ribosomal DNA gene clusters and
      telomere sequences in metaphase spreads of Branchiostoma floridae. We also
      describe how the locations of two single copy genes can be mapped relative to
      each other, and demonstrate this by mapping an amphioxus Pax gene relative to a
      homologue of the Notch gene. These methods have great potential for performing
      comparative genomics between amphioxus and vertebrates.

PMID- 12520095
TI  - Estrogen inhibits development of yolk veins and causes blood clotting in
      transgenic medaka fish overexpressing estrogen receptor.
AB  - We established three transgenic medaka fish lines overexpressing the medaka
      estrogen receptor under the constitutive medaka beta-actin promoter. The
      transgenic embryos became hypersensitive to estrogens (17 beta-estradiol and
      17alpha-ethinylestradiol), and failed to develop yolk veins while blood clots
      formed in the blood island within 3 days after exposure to the estrogens. The
      embryos developed normally if exposed to estrogen after an early neurula stage,
      suggesting that the sensitive stage is before neurulation. The developmental
      defects were recovered by incubation with an anti-estrogen, tamoxifen. These
      results indicate that activation of estrogen receptor caused the estrogen-induced
      developmental defects. Our results show that the transgenic embryos can be used
      to assay the blood clotting activity of estrogenic compounds in vivo.

PMID- 12520096
TI  - New species of Metacaligus (Caligidae, Copepoda) parasitic on the cutlassfish
      (Trichiurus lepturus) of Taiwan, with a cladistic analysis of the family
      Caligidae.
AB  - Metacaligus latus n. sp. (Copepoda, Caligidae) is described from specimens found
      parasitic in the oral and gill cavities of the cutlassfish, Trichiurus lepturus
      Linnaeus, caught from the Strait of Taiwan and landed at Dong-Shih Fishing Port
      in Chiayi County, Taiwan. It is close to M. uruguayensis (Thomsen, 1949), but can
      be distinguished from the latter by the possession of shorter caudal rami in both
      sexes and wider cephalothorax and genital complex in the male. Cladistic
      (phylogenetic) analysis of the Family Caligidae, based on 23 selected
      morphological characters, revealed that Metacaligus Thomsen, 1949 is distantly
      related to Caligus Muller, 1758. It is a valid genus and occurs in sister-group
      relationship with Apogonia Cressey and Cressey, 1990.

PMID- 12520097
TI  - Morphological comparison among Drosophila lini and its two new sibling species
      (Diptera: Drosophilidae).
AB  - Morphological differences are investigated using several culture strains of three
      sibling species collected from Taiwan and Guangdong in China and Pyinoolwin and
      Yangon in Myanmar. Careful examination of male terminalia reveals distinguishable
      differences in the paramere and the aedeagal basal process among the three
      species. In addition, a number of quantitative characters are compared. Kruskal
      Wallis tests with Bonferroni correction, which are carried out separately for
      each sex, detect significant differences in 15 characters, of which two are male
      specific, among the three species. Canonical discriminant analysis using these
      characters reveals that the three species can be distinguished from each other
      with high confidence for both sexes. The results clearly show the presence of
      three good species, Drosophila (Sophophora) lini Bock & Wheeler, 1972 and its two
      new siblings. The new species are described as Drosophila (Sophophora) ohnishii
      sp. nov. from Pyinoolwin and Drosophila (Sophophora) ogumai sp. nov. from Yangon.
      The morphological differentiation among the three sibling species does not
      coincide with the degree of reproductive isolation (based on a previous study).
      The premating isolation pattern suggests two possibilities that premating
      isolation has been evolved or reinforced in sympatric populations between D.
      ohnishii and D. lini and between D. ohnishii and D. ogumai or that it has evolved
      in a very restricted local population of D. ohnishii, possibly by a few
      mutations.

PMID- 12520098
TI  - Polymorphisms and the antiviral property of porcine Mx1 protein.
AB  - We determined the cDNA sequences of the type I interferon-inducible proteins, pig
      Mx1 from PK(15) and LLC-PK1 cells, and compared the antiviral activities of both
      Mx proteins, including Mx1 polymorphisms against vesicular stomatitis virus
      (VSV). Mx1 cDNA derived from PK(15) cells had an 11 bp-deletion in the 3' end of
      the coding region, and was estimated to encode 8 amino acid substitutions and a
      23 amino acid extension compared to that from LLC-PK1 cells. VSV replication was
      inhibited in the 3T3 cells expressing Mx1 mRNA after the cDNA was transfected.
      However, the efficiency of this inhibition was not different between the cells
      expressing Mx1 mRNA from both PK and LLC. These results indicate that pig Mx1
      protein confers resistance to VSV.

PMID- 12520099
TI  - Suppression of transcription activity of the MEQ protein of oncogenic Marek's
      disease virus serotype 1 (MDV1) by L-MEQ of non-oncogenic MDV1.
AB  - Meq is one of the candidate oncogenes in the MDV1 genome. We previously reported
      a difference in the meq open reading frame (ORF) between oncogenic and non
      oncogenic MDV1: L-meq, in which a 180-bp sequence is inserted into the meq ORF,
      is detected in non-oncogenic MDV1. To study the functions of a gene product of L
      meq (L-MEQ), transactivation by L-MEQ was analyzed by dual luciferase assay using
      a reporter gene under the control of long (-1--873 bp) and short (-1 - -355 bp)
      meq promoter (LMP and SMP, respectively). LMP showed higher promoter function
      than SMP. L-MEQ transactivated the expression of the reporter gene, but less than
      MEQ did. In the presence of SMP or the cytomegalovirus immediate-early promoter,
      the same or slightly higher transactivation was observed in cells cotransfected
      with both meq and L-meq than cells transfected only with meq. However, in the
      presence of LMP, lower transactivation was observed in cells cotransfected with
      both meq and L-meq than cells transfected only with meq, suggesting that L-MEQ
      can be a transrepressor. Replication of a vvMDV1 was enhanced in the cells with
      meq. Interestingly, however, replication of vvMDV1 was suppressed in the cells
      with L-meq or with both L-meq and meq, compared to untransfected cells. Thus, L
      MEQ could suppress replication of vvMDV1 displaying the meq gene in coinfected
      cells.

PMID- 12520100
TI  - Diversity (polymorphism) of the meq gene in the attenuated Marek's disease virus
      (MDV) serotype 1 and MDV-transformed cell lines.
AB  - The meq gene encoding a 339-amino-acid bZIP transactivator protein has been
      identified as a candidate oncogene of Marek's disease virus serotype 1 (MDV1),
      which induces malignant lymphomas in chickens. We have previously reported that,
      in addition to meq, L-meq, in which a 180-bp sequence is inserted into the region
      encoding the transactivation domain of meq, is also detected in chickens
      experimentally infected with MDV. To further analyze the diversity in meq, PCR
      was performed using a primer set which specifically amplify the proline-rich
      repeat (PRR) region in the transactivation domain of meq. In CVI988/R6, a vaccine
      strain of MDV1, and JM, an MDV1 strain attenuated by prolonged passage in vitro,
      a major band of a 0.8 kb corresponding to L-meq as well as a minor band of 0.6 kb
      corresponding to meq was detected by PCR. Furthermore, extra 0.5- and 0.3-kb
      bands, corresponding to genes termed as short meq (S-meq), and very short meq (VS
      meq), respectively, were also detected. These genes were also detected in MDV
      transformed cell lines, MSB1 and MTB1. In Md5, an oncogenic MDV1, attenuated by
      prolonged passage in vitro, the 0.6-kb meq was consistently detected, and 0.5-kb
      S-meq was occasionally detected. This diversity in meq was due to the difference
      in the copy number of the PRR region: L-meq and meq contained 9 and 6 copies of
      PRR while 4 and 2 copies of PRR were present in S-meq and VS-meq, respectively.
      Thus, the meq gene is polymorphic in the attenuated MDV1 and the MDV-transformed
      cell lines, and gene products from different meq genes may have different
      functions from each other.

PMID- 12520101
TI  - Distribution of apoptotic cells and apoptosis-related molecules in the developing
      murine palatine rugae.
AB  - Distribution of apoptotic cells and expression of the apoptosis-related factors
      p53, bcl-2 and bad during morphogenesis of the murine palatine rugae (PR) were
      examined histochemically using the terminal deoxynucleotidyl transferase-mediated
      UTP nick end-labeling (TUNEL) technique and specific antibodies against apoptosis
      and cell cycle-related molecules. Formation of the PR rudiment was controlled by
      cell proliferation and apoptosis in the palatal epithelium. TUNEL-positive cells
      were detected only at the epithelial placode area at 12.5-13.5 days post coitus
      (dpc), but only a few cells were positive at the protruding PR area at 14.5-16.5
      dpc. Bcl-2 protein was expressed mainly in the areas outside of those containing
      TUNEL-positive cells at 15.5 -6.5 dpc. P53 protein was not detected throughout
      gestation. Bad was detected in the epithelial layer at 13.5 and 15.5 dpc and
      overlapping the apoptotic area at 13.5-15.5 dpc. Apoptosis of palatal epithelial
      cells might therefore involve spatiotemporally regulated expression of bad during
      murine PR development.

PMID- 12520102
TI  - Complex vertebral malformation in a stillborn Holstein calf in Japan.
AB  - A female stillborn Holstein calf with shortened cervical and thoracic regions,
      protrusion of the tongue, and bilateral symmetric flexural contraction of the
      anterior limbs was delivered on gestation day 281. Multiple hemivertebrae, fused
      and misshaped vertebrae, synostosis and scoliosis of cervical, thoracic and
      lumbar vertebral column were found in the affected calf by radiographic and
      computed tomographic (CT) analysis. Ten pairs of ribs were present and the
      sternum consisted of 9 sternebrae. Multiple morphologic abnormalities including
      fusion, malformation, and displacement, were found in the ribs and sternum.
      Cardiac anomalies, including atrial septal defect and hypertrophy of right
      ventricle, were observed. DNA-polymerase chain reaction (PCR) analysis
      demonstrated that amplified product from the liver DNA of the affected calf had
      identical pattern to that associated with complex vertebral malformation (CVM) of
      Holstein calves and that her dam was a heterozygous carrier of CVM. The affected
      calf was diagnosed as having CVM based on the DNA-PCR results and the
      characteristic findings, and was recorded as a first documentation of CVM
      confirmed in a Holstein calf in Japan.

PMID- 12520103
TI  - Bovine milk enhances the oxidative burst activity of polymorphonuclear leukocytes
      in low concentrations.
AB  - Bovine milk contains various immunoreactive components, and the activation of
      polymorphonuclear leukocytes (PMNLs) function in breast-fed infants has been
      reported. In this study, the effect of milk on the oxidative burst of bovine
      PMNLs was investigated in vitro. When PMNLs were incubated with 0.1% colostrum or
      normal milk, the oxidative burst induced by serum-opsonized Staphylococcus aureus
      was enhanced, and the enhancement declined dose-dependently. The enhancement of
      the oxidative burst by milk was not due to opsonins but the priming activities.
      Also, the phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst increased
      after incubation with 0.1% colostrum, but the colostral enhancement of the
      oxidative burst was unaffected by the incubation time. These results suggest that
      bovine milk contains oxidative burst promoting factor(s).

PMID- 12520104
TI  - Factors affecting transuterine migration of canine embryos.
AB  - Dogs, cats, and pigs have a bicornuate uterus, and transuterine migration of
      embryos occurs in 40% or more of pregnant animals. However, the mechanism of the
      transuterine migration has not been elucidated in dogs. Thus, we investigated the
      occurrence of transuterine migration of embryos when embryos were retained in an
      unilateral uterine tube with more ovulated ova (Experiment 1), when one ovary was
      excised (Experiment 2), and when ova ovulated from the right and left ovaries
      were fertilized with sperm from male dogs with different blood types (Experiment
      3). Transuterine migration of embryos was observed in 7/8 (87.5%), 10/10 (100%),
      and 11/17 (67.4%) fertilized animals in Experiments 1, 2, and 3, respectively. In
      Experiment 3, intrauterine embryo mixing reported in pigs did not occur. These
      findings suggest that transuterine migration of embryos occurs due to the number
      of embryos that enter the uterus but that differences in the number of ovulated
      ova between the right and left ovaries or the number of embryos retained in the
      uterine tube do not affect the migration.

PMID- 12520105
TI  - Diagnostic survey of bovine abortion in Korea: with special emphasis on Neospora
      caninum.
AB  - Causes of bovine abortion were surveyed in Korea within a designated period from
      the cases submitted to the Department of Veterinary Pathology, College of
      Veterinary Medicine, Seoul National University. One hundred and eighty aborted
      fetuses and maternal sera were evaluated by necropsy, histopathology,
      bacteriology, virology, PCR, and serologic tests. The causes of abortion were
      identified in 108 (60%) cases, of which 38 (21.1%) were due to the infection with
      Neospora caninum. None of the 38 cases showed any co-infection with either virus
      or bacteria. Viral and bacterial causes were diagnosed in 28 (15.5%) and 13
      (7.2%) aborted fetuses, respectively. Non-infectious causes such as multiple
      pregnancy, maternal weakness or torsion of umbilical cord were observed in 22
      (12.3%) cases. Results of the present study suggest that N. caninum is believed
      to be the leading cause of bovine abortion in Korea. Thus, more attention should
      be paid to this emerging disease in Korea. However, the causes of many aborted
      fetuses remain undiagnosed in this study. Therefore, this enigma should be
      clarified through further studies such as chromosomal analysis.

PMID- 12520106
TI  - Morphology of the oviduct fluke, Prosthogonimus ovatus, isolated from Indonesian
      native chickens and histopathological observation of the infected chickens.
AB  - Prosthogonimus ovatus infection was detected in 5 of 130 chickens in the oviduct
      and 4 chickens in the bursa of Fabricius. Scanning electron microscopy (SEM)
      revealed that the spines of the P. ovatus were densely distributed on the
      cuticula of the entire dorsal surface of body, but on the ventral surface, they
      were densely present to the level of ventral sucker but gradually decreased in
      density posteriorly, and they could not be seen in the posterior 1/3 area. The
      spines were finger-shaped and denticulate at the tip. Histopathological
      examination showed that polypous elevations, degeneration and exfoliation of the
      mucosal epithelium were detected in the bursa of Fabricius possibly by the
      suction of flukes, in addition to the stratification of the mucosal epithelium,
      and interstitial cell infiltration.

PMID- 12520107
TI  - Penetration of drug resistance in Escherichia coli isolated from laboratory
      animals.
AB  - A total of 713 strains of fecal Escherichia coli (E. coli) isolated from
      laboratory animals in the colonies of 4 research laboratories and 4 commercial
      breeders in Japan in 1994 were examined in regard to resistance to 8
      antibacterial agents. The incidence of resistance to sulfadimethoxine (Su),
      streptomycin (Sm), ampicillin, cephaloridine, tetracycline, chloramphenicol,
      kanamycin, and gentamicin was 99.9%, 32.5%, 6.7%, 0.7%, 7.0%, 2.6%, 6.6% and
      0.7%, respectively. These results indicated that Su and Sm resistance are
      penetrating into normal E. coli strains isolated from laboratory animals.

PMID- 12520108
TI  - Acute vascular and interstitial rejection following renal allograft
      transplantation in dogs.
AB  - Renal allograft transplantation was performed in four beagles. Immunosuppressive
      treatment using cyclosporine, mizoribin and prednisolone was continued from Day 5
      pre- until Day 20 post-transplantation. Between Days 28 and 32 post
      transplantation, an abrupt elevation of the serum creatinine values followed by
      the development of uremia was seen in all recipients. Histopathology of the
      allografts examined between Days 28 and 37 revealed edema, necrosis, hemorrhage
      and severe diffuse interstitial cellular infiltration as well as tubulitis.
      Glomerular changes notably included swelling of the tufts due to
      hypercellularity, which was consistent with transplant glomerulitis. The
      intrarenal arteries exhibited fibrinoid necrosis of the walls and intimal or
      transmural cellular infiltration. These renal lesions were consistent with those
      of acute vascular and interstitial rejection in humans.

PMID- 12520109
TI  - Cytokine profile of a Holstein calf with bovine leukocyte adhesion deficiency
      during the acute-phase inflammatory response.
AB  - Changes in interleukin (IL)-1beta, IL-6 and IL-8 in serum, and their mRNA
      expression on neutrophils from a 4.6-month old Holstein young calf with bovine
      leukocyte adhesion deficiency (BLAD) during the acute phase were evaluated. IL
      1beta concentrations in the serum of the calf with BLAD at age 143-162 days
      ranged from 8.7 to 16.6 ng/ml, whereas the values were less than 2.7 ng/ml in
      control calves. Serum IL-6 (0.04 ng/ml) was only detected on the 1st day when the
      animal was diagnosed with the BLAD. IL-1beta and IL-8 mRNA expression on
      neutrophils from the affected calf appeared to be similar to those of controls.
      Serum cytokine levels and their mRNA expression on neutrophils from the calf with
      BLAD appeared to be little affected by the deficient expression of beta(2)
      integrin on leukocytes, and are considered to be modulated by the inflammatory
      stimuli.

PMID- 12520110
TI  - Studies of certain factors affecting the microenvironment and microflora of the
      external ear of the dog in health and disease.
AB  - A total of 187 dogs, 110 with clinical signs of otitis externa (OE), and 77
      without history or clinical signs of OE, were examined microenvironment and
      microbiological analysis of their ear exudates made. The aural temperature and
      humidity of 160 dogs were measured. There were no significant difference between
      healthy dogs and OE dogs. German shepherd showed relatively lower temperature
      (p<0.01) and higher humidity (p<0.01). The mean log(10) number of microbial
      organisms of ears of OE dogs (4.16 +/- 0.31 cfu/g) was significantly increased,
      compared to that from the ears of non-OE group (2.55 +/- 0.24 cfu/g). Pseudomonas
      spp. and Proteus spp. were detected only from OE dogs. In addition, three
      enterotoxigenic Staphylococcus aureus were isolated from ear specimens.

PMID- 12520112
TI  - Three-dimensional image analysis of a head of the giant panda by the cone-beam
      type CT.
AB  - The cone-beam type CT (Computed Tomography) enabled us to collect the three
      dimensional (3D) digitalized data directly from the animal carcass. In this
      study, we applied the techniques of the cone-beam type CT for a carcass head of
      the giant panda (Ailuropoda melanoleuca) to obtain the 3D images easily without
      reconstruction process, and could morphologically examine the sections from the
      3D data by means of non-destructive observations. The important results of the
      study represent the two following points. 1) We could show the morphological
      relationships between the muscles of mastication and the mandible in non
      destructive status from the 3D data. The exact position of the coronoid process
      could be recognized in the rostro-lateral space of the temporal fossa. 2) By the
      serial sections from the 3D data sets, the morphological characteristics in the
      nasal cavity were detailed with high resolution in this rare species. The nasal
      concha was well-developed in the nasal cavity. The ethmoidal labyrinth was
      encountered immediately caudal to the nasal cavity and close to the region of the
      olfactory bulb. The ethmoidal labyrinth consisted of the complicated osseous
      structure in this area. The data will be useful to discuss the olfactory function
      in the reproduction behavior of this species.

PMID- 12520111
TI  - A new method for counting of quail leukocytes by flow cytometry.
AB  - An automatic counting method was developed for fish blood cells using a
      fluorescent dye, 3, 3-dihexyloxacarbocyanine (DiOC (6)(3)), that selectively
      stain lipid bilayers in living cells. In the present study, the DiOC(6)(3) method
      was applied to quail (Cotumix cotumix japonica) blood cells. After quail blood
      cells were stained with DiOC(6)(3), absolute counts and relative proportions of
      erythrocytes, granulocytes, monocytes, and lymphocytes plus thrombocytes in whole
      blood were obtained by means of flow cytometry (FC). The number of each cell
      types by the FC was in good agreement with those counted microscopically. This
      method will offer new possibilities for routine blood cell counting for avian
      medicine.

PMID- 12520113
TI  - Omental herniation through the esophageal hiatus in a cat.
AB  - A four-year-old male cat was presented with regurgitation. Thoracic radiography
      and contrast radiogram showed a large oval mass and elevated esophagus.
      Exploratory thoracotomy showed omental herniation into the posterior mediastium
      through the esophageal hiatus. Because the mass of the omental herniation was so
      large, celiotomy through a paracostal incision was combined in order to return
      the omentum to its normal position. The diameter of the esophageal hiatus was
      approximately 1 cm but no fibrous adhesion was observed around the hiatus.
      Continuous 1-0 surgical sutures on the hiatus reduced the diameter of the hiatus.
      The cat made a successful postoperative recovery without complications.

PMID- 12520114
TI  - Characteristics of the 16S-23S rRNA intergenic spacer region of Mycoplasma
      haemomuris, previously classified as 'Haemobartonella muris'.
AB  - The intergenic spacer region between the 16S and 23S rRNA genes of Mycoplasma
      haemomuris, previously classified as 'Haemobartonella muris', was amplified by
      PCR and sequenced for analysis of the primary and secondary structures of the RNA
      transcript. The spacer region consisted of 219 base-pairs and lacked the spacer
      tRNA gene. A hypothetical secondary structure predicted in the RNA transcript of
      the spacer region was tentatively assigned box A and box B loci peculiar to the
      members of the Mycoplasma. Mycoplasma haemomuris and the other species of the
      genus Mycoplasma are consistent with these characteristics of the spacer region.

PMID- 12520115
TI  - Experimental infection of cats with Chlamydophila felis.
AB  - Cats experimentally infected with a British isolate of Chlamydophila felis (C.
      felis), B166 strain, by droplet into the eye and nose developed conjunctivitis,
      mild rhinitis and fever. The chlamydophila were first isolated from conjunctiva,
      nictitating membrane and then from lung, tonsil, liver, spleen, kidney, nasal and
      vaginal swabs and blood. These results indicate that C. felis B166 strain first
      infected and replicated in the conjunctiva and nictitating membrane in cats with
      symptoms which were mostly limited to conjunctivitis, and then pervaded the whole
      body by bacteremia.

PMID- 12520116
TI  - Characterization of Staphylococcus aureus strains isolated from bovine mastitis
      in Japan.
AB  - Fifty-three strains of Staphylococcus aureus isolated from cows affected with
      mastitis from 21 prefectures in Japan were characterized by phenotypic and
      genotypic methods. Thirty-three (62.3%) strains showed biotype K-beta+CV:A,
      coagulase type VI, and sensitivity to bovine phages of group III or IV. These 33
      strains could be subdivided into two groups on the basis of the production of
      staphylococcal enterotoxins (SEs) and on toxic shock syndrome toxin-1 (TSST-1).
      By pulsed-field gel electrophoresis, the 16 SEC- and TSST-1-producing strains
      showed similar patterns that differed by only a few fragments, suggesting that
      they were genetically closely related. Fifteen of 17 non SEC-producing strains
      which did not produce any other SEs and TSST-1 were genetically different from
      the SEC-producing strains and showed genetic diversity.

PMID- 12520117
TI  - Effect of intravenous infusion of isotonic sodium bicarbonate solution on
      acidemic calves with diarrhea.
AB  - The effect of 1.35% isotonic sodium bicarbonate solution (ISB) administered
      intravenously on acid-base equilibrium was examined in 18 acidemic Japanese black
      beef calves with spontaneous diarrhea. The infusion volumes of ISB were decided
      based on the first half volumes of base needed. In 72.2% (13/18) of calves,
      improvement of acidemia was detected. There was good correlation (r=0.693,
      p<0.01) between infused volume of ISB and changes in base excess (y=1.097x +
      4.762). Infusion volumes of ISB were 7.5, 10.2, 12.9 and 15.7 ml/kg,
      respectively, enough to correcting the first half of 5, 10, 15 and 20 mEq/l of
      base deficit in acidemic calves. Our finding suggested that ISB could be used to
      correct metabolic acidosis without altering electrolyte concentrations in calves.

PMID- 12520119
TI  - Spectrophotometric and potentiometric determination of piroxicam and tenoxicam in
      pharmaceutical preparations.
AB  - Two simple and accurate methods are described for the determination of piroxicam
      and tenoxicam in their pharmaceutical preparations. The spectrophotometric method
      involves the oxidation of these drugs with potassium iodate in acid medium with
      the liberation of iodine and subsequent extraction with cyclohexane followed by
      measuring the absorbance at lambda=522 nm. Beer's law is obeyed in the
      concentration range of 0.05-1.1 and 0.05-0.6 mg x ml(-1) for piroxicam and
      tenoxicam, respectively. The apparent molar absorptivities of the resulting
      coloured products are found to be 2.7 x 10(3) and 2.5 x 10(3) l mol(-1) x cm(-1),
      whereas Sandell sensitivities are 0.012 and 0.013 g x cm(-2) for piroxicam and
      tenoxicam, respectively. The potentiometric method involves the direct titration
      of both drugs with N-bromosuccinimide in acid medium and the end point is
      determined potentiometrically using platinum indicator electrode. Piroxicam and
      tenoxicam can be determined quantitatively in the concentration range of 0.33
      3.37 and 0.33-4.08 mg x ml(-1) for tenoxicam and piroxicam, respectively. The
      standard deviation and relative standard deviation values are found to be ranged
      from 0.05-0.07 and 0.37-0.98% and 0.025-0.078 and 0.25-1.2% for tenoxicam and
      piroxicam, respectively. The two methods are accurate within +/-1.0%. Optimum
      conditions affecting both methods are studied. The proposed methods are applied
      for the determination of the drugs in pure form and in commercial pharmaceutical
      preparations.

PMID- 12520118
TI  - Preparation of dry powder inhalation by surface treatment of lactose carrier
      particles.
AB  - An attempt was made to produce carrier particles for dry powder inhalations by
      the surface treatment of lactose particles with aqueous ethanol solution.
      Drug/carrier powder mixtures were prepared consisting of lactose carriers with
      different particle surface properties and micronized salbutamol sulfate. These
      powder mixtures were aerosolized by Spinhaler, and in vitro deposition properties
      of salbutamol sulfate were evaluated by twin impinger. The degree of adhesion
      between drug particles and carrier particles was determined by the
      ultracentrifuge separation method. In addition, the air jet sieve method was used
      to evaluate characteristics of the separation of drug particles from carrier
      particles in airflow. The average adhesion force (F50) between the surface
      treated lactose carrier and drug particles was significantly lower than that of
      powder mixed with the untreated lactose carrier, indicating that the degree of
      separation (T50) of drug particles from carrier particles was improved when
      surface-treated lactose carrier was used. This resulted in an improvement of in
      vitro inhalation properties.

PMID- 12520120
TI  - Novel method to control release of lipophilic drugs with high potency from
      silicone.
AB  - Silicone has been utilized as a carrier material for sustained release system of
      lipophilic drugs. Extensive studies revealed that drug release rate is influenced
      by factors such as physicochemical properties of the drug and additives.(1-5))
      When a lipophilic drug is highly potent at low concentrations, the drug release
      rate should be strictly controlled so as to avoid side effects. In this study,
      using vitamin D(3) (VD(3)) as an example of such drugs, we investigated novel
      method to suppress initial burst and to modify drug release rate from silicone
      matrix. As a result, it was found that (a). addition of human serum albumin (HSA)
      suppressed initial burst and enhanced release rate in the later stage, resulting
      constant release of VD(3), (b). covering a matrix formulation with a membrane of
      low diffusivity (core-rod formulation) suppressed initial burst and released drug
      in a constant rate, and (3) using materials for which the drug has high affinity
      as dissolution solvent (reservoir formulation), the drug release rate was
      reduced.

PMID- 12520121
TI  - Novel drug delivery device using silicone: controlled release of insoluble drugs
      or two kinds of water-soluble drugs.
AB  - Drug release mechanism from silicone carrier differs depending on physicochemical
      properties of the drug. So far, there have been few reports on controlled release
      of insoluble drug and on simultaneous release of two kinds of water-soluble
      drugs. The purposes of this study are to establish methods for (1). continuous
      release of insoluble drug, and (2). release of two kinds of water-soluble drugs
      from silicone carrier. Polystyrene beads (PSTB) and proteins such as interferon
      (IFN) and human serum albumin (HSA) were used as model drugs. PSTB was released
      from silicone only when citric acid (CA) and sodium bicarbonate (SB) existed as
      additives. The release patterns of IFN and HSA were almost same in the case of
      matrix and covered-rod formulations, but double-layered formulation released them
      in different patterns. As far as we are aware, this is the first report on the
      release of insoluble drug from silicone and the controlled release of two kinds
      of water-soluble drugs.

PMID- 12520122
TI  - The absolute configuration of (+)-oxopropaline D by theoretical calculation of
      specific rotation and asymmetric synthesis.
AB  - The specific optical rotations of (R)-oxopropaline D calculated by two ab initio
      MO methods were +52+/-31 degrees and +61+/-29 degrees, respectively, and (+)
      oxopropaline D (3) was presumed to have an R-configuration. On the basis of this
      theoretical result, the reaction of 1-litio-beta-carboline with (R)
      glyceraldehyde acetonide followed by oxidation with MnO(2) gave (R)-oxopropaline
      D acetonide (4a), which was consistent with the previously synthesized (+)
      oxopropaline D acetonide (4) in all respects. From the results of theoretical
      calculations and the experimental synthesis, we determined that natural (+)
      oxopropaline D (3) has an R-configuration.

PMID- 12520123
TI  - Heat-accelerated degradation of solid-state andrographolide.
AB  - The stability of andrographolide, the major active diterpene lactone from
      Andrographis paniculata (BURM. f.) WALL. ex NEES., was determined to show that,
      while crystalline andrographolide was highly stable even at 70 degrees C (75%
      relative humidity) over a period of 3 months, its amorphous phase degraded
      promptly. Heat-accelerated conditions revealed second-order kinetics of the
      decomposition with the rate constant at 25 degrees C (k(25 degrees C)) predicted
      from the Arrhenius plot of 3.8 x 10(-6) x d(-1). The major decomposed product
      under elevated temperature (70 degrees C, 75% relative humidity) is 14-deoxy
      11,12-didehydroandrographolide.

PMID- 12520124
TI  - Synthesis and DNA strand breakage activity of some 1,4-diazepines.
AB  - Reactions of 1,3-propanediamine with alpha-dicarbonyl compounds (1a-e) were
      examined and various condensed heterocyclic compounds such as 1,4-diazepines (2)
      and 3-pyrimidine derivatives (3) were obtained. Some of 1,4-diazepines (2) showed
      DNA strand breakage activity.

PMID- 12520125
TI  - Water-soluble constituents of coriander.
AB  - From the water-soluble portion of the methanol extract of coriander (fruit of
      Coriandrum sativum L.), which has been used as a spice and medicine since
      antiquity, 33 compounds, including two new monoterpenoids, four new monoterpenoid
      glycosides, two new monoterpenoid glucoside sulfates and two new aromatic
      compound glycosides were obtained. Their structures, were clarified by spectral
      investigation.

PMID- 12520126
TI  - Improvement of physicochemical properties of N-4472. Part III. VC/N-4472 complex
      formation and self-association in aqueous solution.
AB  - To improve the aqueous solubility of a poorly water-soluble drug, N-[2-(3,5-di
      tert-butyl-4-hydroxyphenethyl)-4,6-difluorophenyl]-N'-[4-(N-benzylpiperidyl)]urea
      (N-4472), organic acid/N-4472 evaporates were prepared by using succinic acid, L
      tartaric acid, citric acid and L-ascorbic acid (VC). Among these evaporates, only
      the VC/N-4472 evaporate at a molar ratio of more than 2 (VC/N-4472) formed stable
      colloidal particles (with a mean particle size <or=100 nm) in aqueous solution.
      In particular, the evaporate prepared at the molar ratio of 5 (VC/N-4472) formed
      a clear solution comprising fine particles with a narrow particle size
      distribution of 8-15 nm. On the basis of surface tension measurement, zeta
      potential determination and static light scattering measurement, it was
      conceivable that both N-4472 and VC contributed to the formation of a surface
      active complex in aqueous solution, while the colloidal particles could be
      interpreted as the self-association product of these complexes. According to the
      findings on (1)H-NMR and attenuated total reflectance Fourier transform infrared
      spectra, it was postulated that upon combining both components at a molar ratio
      of 2 (VC/N-4472), a 1 : 1 association complex of N-4472 and VC was formed,
      whereas the higher order complexes were assumed formed with use of a molar ratio
      of more than 2 (VC/N-4472). Furthermore, it was evidenced that all of these
      complexes were composed of amphiphilic structures comprising both hydrophobic N
      4472 moiety and hydrophilic VC moiety, thereby properly accounting for surface
      active property of these complexes.

PMID- 12520127
TI  - Constituents of Holothuroidea, 13. Structure of neuritogenic active ganglioside
      molecular species from the sea cucumber Stichopus chloronotus.
AB  - Three ganglioside molecular species, SCG-1, SCG-2, and SCG-3, were obtained from
      the lipid fraction of the chloroform-methanol extract of the sea cucumber
      Stichopus chloronotus. On the basis of chemical and spectroscopic evidence, the
      structures of these gangliosides have been determined to be 1-O-[(N-glycolyl
      alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (SCG-1), 1-O-[8-O
      sulfo(major)-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]
      ceramide (SCG-2), and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D
      neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (SCG-3). The ceramide
      moieties were composed of heterogeneous long-chain base and fatty acid units. SCG
      3 is the first type of ganglioside containing a fucopyranose in the sialosyl
      trisaccharide moiety. Moreover, these three gangliosides exhibited neuritogenic
      activity toward the rat pheochromocytoma PC12 cells in the presence of nerve
      growth factor.

PMID- 12520128
TI  - Determination of ofloxacin in tablets by room-temperature phosphorimetry on a
      poly(vinyl alcohol) solid substrate.
AB  - An easy and sensitive method for the quantitative determination of ofloxacin
      (OFLX), a new fluoroquinolone antimicrobial agent, in a pharmaceutical
      formulation, tablet, was developed by using solid-substrate room-temperature
      phosphorimetry (RTP) on a poly(vinyl alcohol) substrate. The method did not
      require a dry gas flush during the measurement of phosphorescence. The influence
      of different conditions such as solution pH and concentrations of heavy atoms,
      used as the enhancer, were studied. The phosphorescence intensity of OFLX was
      enhanced using NaOH and KI as enhancers. A linear relationship between
      concentration and RTP intensity for each standard solution was obtained in the
      concentration range of 4-18000 ng/ml, and the determination limit was 4 ng/ml.
      The proposed method was applied to a determination of OFLX in a commercial
      tablet, and the results were compared with those of fluorescence and UV methods.
      It was proven that OFLX in a commercial tablet can be accurately measured by this
      method with a very small amount of sample solution.

PMID- 12520129
TI  - Naucleamides A-E, new monoterpene indole alkaloids from Nauclea latifolia.
AB  - Five new monoterpene indole alkaloids, naucleamides A-E (1-5), were isolated from
      the bark and wood of Nauclea latifolia, and the structures and relative
      stereochemistry were elucidated from the spectroscopic data. Naucleamide E (5) is
      a unique monoterpene indole alkaloid possessing a pentacyclic ring system with an
      amino acetal bridge.

PMID- 12520130
TI  - Medicinal foodstuffs. XXXI. Structures of new aromatic constituents and
      inhibitors of degranulation in RBL-2H3 cells from a Japanese folk medicine, the
      stem bark of Acer nikoense.
AB  - Four new aromatic constituents, rhododendroketoside, (-)-sakuraresinoside,
      acernikol, and nikoenoside, were isolated from a Japanese folk medicine, the stem
      bark of Acer nikoense MAXIM. The structures of the new constituents were
      determined on the basis of chemical and physicochemical evidence. The principle
      cyclic diarylheptanoids were found to show inhibitory effects on the release of
      beta-hexosaminidase in RBL-2H3 cells.

PMID- 12520131
TI  - Four guaianolides from Sinodielsia yunnanensis.
AB  - Four new guaianolides, sinodielides A-D (1-4), were isolated from Sinodielsia
      yunnanensis WOLFF together with a known polyacetylene, falcarindiol, and two
      known coumarins, bergapten and scopoletin. Their structures were established by
      spectral and X-ray analyses.

PMID- 12520132
TI  - Transformation of Cinchona alkaloids into 1-N-oxide derivatives by endophytic
      Xylaria sp isolated from Cinchona pubescens.
AB  - The microbial transformation of four Cinchona alkaloids (quinine, quinidine,
      cinchonidine, and cinchonine) by endophytic fungi isolated from Cinchona
      pubescens was investigated. The endophytic filamentous fungus Xylaria sp. was
      found to transform the Cinchona alkaloids into their 1-N-oxide derivatives.

PMID- 12520133
TI  - Preparation of new nitrogen-bridged heterocycles. 53. Syntheses of 3
      (benzylthio)thieno[3,4-b]indolizine derivatives and their intramolecular arene
      arene interactions.
AB  - Various ethyl 1-arylcarbonyl-3-[(un)substituted methylthio]thieno[3,4
      b]indolizine-9-carboxylates were synthesized in good yields by a novel
      methodology in which the S-alkylation of 5-arylcarbonyl-4-ethoxycarbonylmethyl-3
      (1-pyridinio)thiophene-2-thiolates with alkyl or benzyl halides, the 1,5-dipolar
      cyclization of the resulting pyridinium salts in the presence of a base, and the
      aromatization were performed. In the X-ray analyses of some 3
      (benzylthio)thieno[3,4-b]indolizine-9-carboxylates, a gauche and two anti
      conformers in relation to the exocyclic sulfide linkage were found.
      Interestingly, all of the 3-(benzylthio)thieno[3,4-b]indolizine derivatives
      showed significant high-field shifts (delta up to 0.3 ppm) for the 5- and 6
      proton signals compared with those of the 3-methylthio derivatives in the (1)H
      NMR spectra and exhibited a definite absorption band near 425 nm in their UV
      spectra, indicating an intramolecular arene-arene interaction between the
      thieno[3,4-b]indolizine and the phenyl ring.

PMID- 12520134
TI  - Three new trimeric stilbenes from Gnetum gnemon.
AB  - Three stilbene trimers (gnemonols D, E, F) were isolated from the root of Gnetum
      gnemon. The structures were determined by spectroscopic analysis. In addition,
      the antioxidant activity of the compounds on lipid peroxide inhibition and super
      oxide scavenging activity were also investigated.

PMID- 12520135
TI  - New triterpenoids from Gentiana lutea.
AB  - Three new triterpenoids, 2,3-seco-3-oxours-12-en-2-oic acid, 2,3-seco-3-oxoolean
      12-en-2-oic acid, and betulin 3-O-palmitate, have been isolated from the rhizomes
      and roots of Gentiana lutea, together with five known ones. The structures of the
      new compounds were determined by spectral and chemical methods.

PMID- 12520136
TI  - Norlanostane and lanostane glycosides from the bulbs of Chionodoxa luciliae and
      their cytotoxic activity.
AB  - Ten lanostane glycosides (1-10), including two new norlanostane glycosides (2 and
      7) and a new lanostane glycoside with a spirolactone ring system (9), were
      isolated from the fresh bulbs of Chionodoxa luciliae (Liliaceae). The structures
      of the new compounds were determined on the basis of extensive spectroscopic
      analysis and the results of hydrolytic cleavage to be (23S)-3beta-[(O-beta-D
      apiofuranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->3)]-O-beta-D-glucopyranosyl
      (1-->2)-alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranosyl)oxy]-17alpha,23
      epoxy-28,29-dihydroxy-27-norlanost-8-en-24-one (2), (23S)-17alpha,23-epoxy-29
      hydroxy-3beta-[(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-
      >2)-beta-D-glucopyranosyl-(1-->3)]-O-beta-D-glucopyranosyl-(1-->2)-alpha-L
      arabinopyranosyl-(1-->6)-beta-D-glucopyranosyl)oxy]-27-norlanost-8-ene-15,24
      dione (7), and (23S,25R)-17alpha,23-epoxy-29-hydroxy-3beta-[(O-alpha-L
      rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->3)]-O-beta-D-glucopyranosyl
      (1-->2)-alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranosyl)oxy]lanost-8-en
      23,26-olide (9), respectively. The cytotoxic activity of the isolated compounds
      against HSC-2 human oral squamous cell carcinoma cells are also reported.

PMID- 12520137
TI  - Stereospecific synthesis of azetidine-cis-2,3-dicarboxylic acid.
AB  - Electrocyclic reaction product of 1-(methoxycarbonyl)-1,2-dihydropyridine was
      stereospecifically converted by RuO(4) oxidation into azetidine-cis-2,3
      dicarboxylic acid.

PMID- 12520138
TI  - A facile preparation of 1-(6-hydroxyindol-1-yl)-2,2-dimethylpropan-1-one.
AB  - An effective synthesis of 1-(6-hydroxyindol-1-yl)-2,2-dimethylpropan-1-one (4)
      was developed starting from 1H-indole (2). The key step involved suitable
      utilization of 4-(1-pyrrolidino)pyridine for the removal of the chloroacetyl
      moiety from chloroacetic acid 1-(2,2-dimethylpropionyl)-1H-indol-6-yl ester (3);
      a possible mechanism is, also, presented. Compound 4 might lead to selectively
      substituted derivatives, either on the phenolic-OH or the indolyl-NH, with
      putative biological interest. In this respect, we found that the core structure
      of 1H-indol-6-ol (1) possesses a degree of aldose reductase inhibitory potential,
      at a concentration of 100 microM.

PMID- 12520139
TI  - Synthesis of aminocyclohexitol via carbon-carbon bond-forming radical cyclization
      of oxime ether.
AB  - The stannyl radical mediated-cyclization of oxime ether, derived from D-glucose,
      gave the aminocyclohexitol derivative. Stereoselective C-C bond forming
      cyclization proceeded via favorable conformers minimizing A(1,3)-strain between
      the oxime ether group and alpha-substituents.

PMID- 12520140
TI  - A new route to (+)-estrone using a bicyclo[3.2.1]octane chiral building block.
AB  - A new route to (+)-estrone has been developed starting from the chiral building
      block having a bicyclo[3.2.1]octane framework based on the inherent
      stereochemical chemical nature of the chiral building block.

PMID- 12520141
TI  - Anti-smoking declaration: a message from the Japanese Circulation Society.

PMID- 12520142
TI  - Changing spectrum of infective endocarditis: review of 194 episodes over 20
      years.
AB  - A review of admission records identified 194 episodes of infective endocarditis
      (IE) from January 1980 to December 1999 at a community hospital in Tokyo. The
      cases were divided into decades, and the clinical picture and short-term outcomes
      were compared and analyzed. The mean age of patients in the 1990s was older (45.5
      +/-13.2 vs 55.1+/-12.6 years, p<0.001), and prosthetic valve endocarditis was
      significantly more frequently seen (14.4% vs 31.8%, p=0.004). None had a history
      of intravenous drug abuse (IVDA). Patients on chronic hemodialysis comprised 5.8%
      of IE cases in the 90s. Overall, dental procedure or caries still remained the
      main presumed source of infection. Staphylococcal IE showed a tendency to
      increase, and methicillin-resistant staphylococcal IE was significantly prominent
      in the 90s (0% vs 10.4%, p=0.0006). The overall in-hospital mortality was similar
      between the 2 groups (13.6% vs 18.8%, NS). Multivariate analysis found
      neurological abnormality, renal insufficiency and staphylococcal IE as predictors
      of in-hospital mortality. The characteristics of IE in Japan have changed, even
      among non-IVDA patients, and it appears to occur in a more high-risk patient
      population, which may warrant a more aggressive therapeutic approach to its
      management and treatment.

PMID- 12520143
TI  - New ECG criteria for high-risk Brugada syndrome.
AB  - To identify high-risk patients with Brugada syndrome, the present study reviewed
      60 standard 12-lead electrocardiograms from 60 patients collected by the Japanese
      Brugada syndrome registry. Under blinded conditions, the S wave of lead V(1) was
      measured from the tip of r to r', and the amplitude of the ST segment in lead
      V(2) was measured at 0.08 s from the J point. In patients with ventricular
      fibrillation (n=17), the S wave was significantly longer in V(1) (0.085+/-0.007 s
      vs 0.075+/-0.011 s, p=0.001), and ST segment elevation in V(2) was significantly
      greater (0.323+/-0.133 mV vs 0.236+/-0.129 mV, p=0.012) than in patients without
      fibrillation. An S wave width of 0.08 s or more in V(1) had a positive predictive
      value of 40.5% and negative predictive value of 100% for ventricular
      fibrillation, with 100% sensitivity. ST elevation of 0.18 mV or more in V(2) had
      a positive predictive value of 37.8% and a negative predictive value of 100% for
      ventricular fibrillation, with 100% sensitivity. Both an S wave width > or =0.08
      s in V(1) and ST elevation > or =0.18 mV in V(2) were highly specific indicators
      of ventricular fibrillation and are proposed as new criteria for high-risk
      Brugada syndrome.

PMID- 12520144
TI  - Evaluation of the effect of bepridil on paroxysmal atrial fibrillation:
      relationship between efficacy and the f-f interval in surface ECG recordings.
AB  - Bepridil, a multi-ion channel blocker, is effective for some types of cardiac
      arrhythmias, and so its effect on the paroxysmal atrial fibrillation (PAF) was
      evaluated in the present study, comparing it with class Ic antiarrhythmic drugs.
      The relationship between efficacy and the f-f interval in the surface ECG
      recording was also analyzed. Sixty-one symptomatic PAF patients were randomized
      to a bepridil group (200 mg/day, n=23) or class Ic drug group (flecainide 100-200
      mg/day or pilsicainide 75-150 mg/day, n=38). The drug was considered effective
      for PAF prevention when symptomatic episodes of PAF were decreased to less than
      50% during the follow-up period of 2-6 months. The f-f interval in the surface 12
      lead ECG trace was evaluated during a PAF episode. Both bepridil and the class Ic
      drugs were effectively prevented PAF (15/23 (65.2%) vs 24/38 (63.1%) patients,
      NS). In the class Ic drug group, the f-f interval was longer in the effective
      cases (114+/-48 ms) than in the non-effective cases (68+/-26 ms, p=0.0002). In
      contrast, in the bepridil group the f-f interval was shorter in the effective
      cases (85+/-26 ms) than in the non-effective ones (152+/-45 ms, p=0.0005). When
      comparing the non-effective cases in the 2 groups, the bepridil group showed a
      significantly longer f-f interval than the class Ic drug group (p=0.0003). As a
      result of drug administration, the class Ic drugs prolonged the f-f interval from
      78+/-33 ms to 128+/-46 ms (p=0.0004) whereas bepridil showed no change (109+/-39
      ms vs 135+/-47 ms). For clinical PAF prevention, the effect of bepridil matched
      that of class Ic antiarrhythmic drugs. Because bepridil was effective in PAF
      patients with relatively shorter f-f intervals without prolonging the f-f
      interval, bepridil is considered to work mainly as a class III antiarrhythmic
      drug.

PMID- 12520145
TI  - Mitochondrial 5178A/C genotype is associated with acute myocardial infarction.
AB  - A single nucleotide polymorphism of mitochondrial 5178A/C, causing a Met to Leu
      replacement within the NADH dehydrogenase subunit, is reported to be associated
      with longevity. The purpose of the present study was to assess the contribution
      of mitochondrial polymorphisms, particularly the 5178A/C genotype, to the
      susceptibility to acute myocardial infarction (AMI) in a Japanese study
      population. There were 4 groups: 150 patients with AMI, 150 with essential
      hypertension, 100 with diabetes mellitus, and 150 subjects matched for age and
      sex who served as the control group. Mitochondrial 5178A/C was detected by the
      polymerase chain reaction restriction fragment length polymorphism method. The
      allelic frequency of 5178C was significantly higher in the AMI group than in the
      control group, and this difference was more marked in younger patients. There
      were differences in allelic frequencies among the essential hypertension group,
      diabetes mellitus group and control group, but a higher frequency of the C allele
      was seen in the AMI group compared with the essential hypertension and diabetes
      mellitus groups. This particular polymorphism was found to be associated with
      development of AMI, especially in younger patients and constitutes a new risk
      factor for AMI.

PMID- 12520146
TI  - Comparison of cutting balloon vs stenting alone in small branch ostial lesions of
      native coronary arteries.
AB  - Angioplasty of small vessels is associated with a higher rate of restenosis, even
      in the ostium. The present study compared the acute, late results of cutting
      balloon vs those of stenting alone in small branch ostial lesions of native
      coronary arteries and the effect on the parent vessel. The study group comprised
      61 patients with successful angioplasty of smaller branch ostial lesions in
      native coronary arteries. The reference vessel diameter was between 2.5 and 3.0
      mm. Patients were divided into 2 groups: group I (cutting balloon, n=30) and
      group II (stenting alone, n=31). After intervention, patients in group II
      achieved significant acute lumen gain, larger minimal lumen diameter (MLD) and
      less diameter stenosis. At 3-month follow-up, the MLD and diameter stenosis of
      the 2 groups were almost identical; however, late loss was lower in group I. At
      the 6-month follow up, the cumulative restenosis rate was 41% (11/27) in group I
      compared with 63% (19/31) in group II (p=0.05), and the target lesion
      revascularization was also lower in the cutting balloon group [29% (8/27) vs 53%
      (16/30) p=0.05]. In group 1, the MLD of the parent vessel did not change before,
      after cutting balloon or at follow-up. In contrast, there were significant
      reductions in parent vessel MLD following stenting alone and at follow-up. Plaque
      shift did not occur in the cutting balloon group. Cutting balloon angioplasty is
      a feasible approach for the treatment of small branch ostial lesions and does not
      cause significant narrowing of the parent vessel.

PMID- 12520147
TI  - Association between hepatitis C virus core protein and carotid atherosclerosis.
AB  - A link between certain infectious microorganisms and an increased risk of
      atherosclerotic disease has been suggested. By analyzing the data of subjects who
      had undergone general health-screening tests, a possible association between
      carotid atherosclerosis and seropositivity of antibody against hepatitis C virus
      (HCV) has been previously reported. In the present study, a possible link between
      carotid atherosclerosis and HCV core protein positivity was assessed, because it
      is postulated to be a better marker of viremia and thus persistent infection. Of
      the 1992 enrolled subjects, 496 (25%) had carotid artery plaque, and 25 (1.3%)
      were positive for HCV core protein. Carotid artery plaque was positive in
      480/1967 (24%) and 16/25 (64%) of the core protein-negative and core protein
      positive subjects, respectively (p<0.0001 by chi(2) test). Serum concentrations
      of transaminases were higher in core protein-positive subjects, but albumin
      concentrations were not significantly different between the 2 groups.
      Multivariate logistic regression analysis showed that HCV core protein positivity
      is an independent predictor of carotid plaque with an odds ratio of 5.61 (95%
      confidence interval 2.06-15.26, p<0.001). These data further support the possible
      link between persistent HCV infection and carotid atherosclerosis in the subjects
      without severe liver dysfunction.

PMID- 12520148
TI  - Noncardioplegic surgery for ischemic mitral regurgitation.
AB  - Twenty-seven consecutive patients underwent surgery for ischemic mitral
      regurgitation (MR): papillary muscle rupture (1), papillary muscle dysfunction
      (11) and annular dilatation (15). The grade of MR was moderate or severe, and the
      ejection fraction (EF) was less than 30% in 8 patients (mean, 43%). Three cases
      were reoperation and 3 were emergencies. Under ventricular fibrillation (VF) and
      intermittent aortic cross-clamping at moderate hypothermia, coronary artery
      bypass grafting (CABG) was performed first, followed by the mitral procedure
      through a right-sided left atriotomy (repair 21, replacement 6) performed under
      VF with the heart perfused through the native coronary arteries and CABG grafts.
      Concomitant procedures were CABG (23), Dor's procedure (5), and tricuspid
      annuloplasty (3). In one reoperative case with cardiogenic shock, CABG was
      impossible because of dense adhesions and the patient died just after surgery
      (hospital mortality, 3.7%). Five patients required intra-aortic balloon pump
      (IABP) support intraoperatively, but none required prolonged (> or =7 days)
      inotropic support or IABP use, although the serum concentrations of creatine
      kinase and its myocardial fraction were elevated remarkably. Other morbid events
      were refractory ventricular arrhythmia in one case and stroke in another. Median
      duration of mechanical ventilation and intensive care unit stay was 8 h and 3
      days, respectively. Mean EF at hospital discharge was 48%. The extended period of
      VF was not associated with unfavorable clinical outcomes. Noncardioplegic surgery
      for ischemic MR was carried out with acceptable mortality and morbidity, and can
      be a good alternative, especially when clamping the aorta is undesirable.

PMID- 12520149
TI  - Effect of intraaortic balloon pumping on left ventricular function in patients
      with persistent ST segment elevation after revascularization for acute myocardial
      infarction.
AB  - The purpose of the present study was to assess the impact of intraaortic balloon
      pumping (IABP) in patients with persistent ST elevation who underwent
      revascularization within 6 h of their first acute anterior myocardial infarction
      (AMI). Persistent ST elevation after revascularization was defined as being > or
      =50% of the initial value on return to the coronary care unit. Twenty-four
      patients were treated without IABP (control group) and 27 patients were treated
      with IABP (IABP group). There was no significant difference between the 2 groups
      in pretreatment left ventricular ejection fraction (LVEF), end-diastolic volume
      index or end-systolic volume index. After 137+/-46 days, the change in the LVEF
      was significantly higher in the IABP group than in the control group (5+/-13% vs
      13+/-15%, p=0.04). However, the left ventricular end-diastolic volume index was
      similar between the 2 groups during follow-up (pretreatment: 77+/-19 ml/m(2) vs
      74+/-13 ml/m(2), p=0.54; follow-up: 86+/-22 ml/m(2) vs 83+/-18 ml/m(2), p=0.60).
      These data suggest that IABP enhances the improvement in LVEF independent of
      remodeling in AMI patients with persistent ST elevation after revascularization.

PMID- 12520150
TI  - Event rates of acute myocardial infarction and coronary deaths in Niigata and
      Nagaoka cities in Japan.
AB  - Mortality from coronary heart disease in Japan is the among lowest recorded in
      the industrialized nations; however, little is known about the rate of events
      including nonfatal cases. A survey of event registration and a review of death
      certificates was carried out to estimate event rates of acute myocardial
      infarction (AMI) and coronary deaths in the largest 2 cities of the Niigata
      prefecture where there are 480,720 residents aged between 15 and 65 years. The
      definitions for these cardiac events used for the WHO-MONICA project were:
      (1)'definite AMI', (2) 'possible AMI or coronary death' (not including
      unclassifiable fatal events), and (3) 'unclassifiable fatal events'. Age-adjusted
      rates for AMI and coronary deaths (per 100,000/year) according to the
      registration survey were 54.6 for men and 7.2 for women according to definition 1
      and 41.9 for men, and 5.3 for women according to definition 2. When data from the
      death certificate review were taken into account for the estimation, these rates
      increased to 80.6 for men and 14.2 for women according to definition 1, and 50.0
      for men and 9.0 for women according to definition 2. These estimated rates are
      considerably lower than those in other industrialized nations surveyed in the WHO
      MONICA project, and these findings are consistent with those from other studies
      conducted in Japan.

PMID- 12520151
TI  - Acute massive pulmonary thromboembolism associated with risperidone and
      conventional phenothiazines.
AB  - To assess the contribution of antipsychotic medication in Japanese patients
      suffering acute massive pulmonary thromboembolism, records of patients with
      idiopathic pulmonary thromboembolism associated with antipsychotic medication who
      were seen in a Japanese Emergency Center from January 1996 to December 2000 were
      reviewed. Age, gender, physical status, clinical presentation, antiphospholipid
      antibody, outcome, psychiatric profile, and antipsychotic medication use were
      examined. Seven patients had acute pulmonary thromboembolism associated with
      antipsychotic drug use, representing 44% of all patients with idiopathic
      pulmonary thromboembolism. The 7 patients developed symptoms in the early
      morning. More women than men were affected. In 5 cases, chlorpromazine and other
      phenothiazines had been prescribed, whereas in 2 cases, risperidone, a mixed
      serotonin 5HT(2A) and dopamine D(2) receptor antagonist, had been taken for 40
      days and 6 days, respectively. In 4 cases, including the patients taking
      risperidone, antiphospholipid antibodies were not present. Although statistically
      significant conclusions can not be drawn from this study, the data suggest that
      patients receiving risperidone, as well as conventional phenothiazines, are at
      risk for acute pulmonary thromboembolism, even if otherwise healthy. Strong
      affinity for the 5HT(2A) receptor of the novel antipsychotic may increase
      coagulability and the risk of thromboembolism.

PMID- 12520152
TI  - Color kinesis during contrast-enhanced dobutamine stress echocardiography:
      feasibility and applicability.
AB  - Accurate interpretation of dobutamine stress echocardiography (DSE) needs
      expertise. Color kinesis (CK) allows objective assessment of wall motion (WM),
      and its feasibility and accuracy are enhanced under harmonic imaging with
      contrast agents. To explore its utility, CK was performed in 41 unselected
      patients during contrast-enhanced DSE. After bolus injection of Levovist, the CK
      image was acquired in the apical 4- and 2-chamber views at baseline and peak
      stress using the ultraharmonic mode. Quad screen format with second harmonic
      imaging after another injection of Levovist was also obtained as a reference.
      Regional WM (12 segments in the apical view) was independently assessed by both
      methods. Heart rate increased from 67 beats/min at baseline to 135 beats/min (88%
      of age predicted maximal heart rate) at peak stress. The CK image was
      successfully obtained in all patients at baseline and in 38/41 patients at peak
      stress. CK tracked endocardial motion accurately in 93% (456/492) of left
      ventricular segments at baseline and 87% (427/492) at peak stress. The
      concordance rate of normal and abnormal WM between the 2 methods was 86%
      (392/456, Kappa 0.61) at baseline and 85% (362/427, kappa 0.53) at peak stress.
      Among the 38 patients in whom both methods were completed, the standard quad
      screen display showed abnormal DSE results in 17 patients and 28/114 vascular
      territories. The sensitivity, specificity and diagnostic accuracy of CK for
      detecting abnormal findings were, respectively, 71% (12/17), 90% (19/21) and 82%
      (31/38) in patients and 57% (16/28), 97% (83/86) and 87% (99/114) in vascular
      territories. The application of CK was highly feasible during contrast-enhanced
      DSE and gave an objective assessment of WM. This method can be a valuable adjunct
      to the conventional interpretation of DSE.

PMID- 12520153
TI  - Significance of monocyte chemotactic protein-1 and thymidine phosphorylase in
      angiogenesis of human cardiac myxoma.
AB  - Angiogenesis is indispensable to tumor development and proliferation. The aim of
      this study was to investigate whether the expression of monocyte chemotactic
      protein-1 (MCP-1) and of thymidine phosphorylase (TP) correlates with the
      angiogenesis and clinicopathologic features in cardiac myxoma. Paraffin-embedded
      specimens of 17 resected cardiac myxomas were immunohistochemically stained for
      MCP-1, CC chemokine receptor-2 (CCR-2), TP, CD31, and CD68. Correlations among
      MCP-1 expression, TP expression, microvessel count (determined by CD31 staining),
      macrophage count (determined by CD68 staining), and the clinicopathologic
      features of the patients were analyzed statistically. Immunohistochemical
      analysis revealed that MCP-1 and TP were expressed in myxoma cells, as well as in
      stromal cells such as infiltrating cells, fibroblast-like cells and endothelial
      cells. CCR-2 was abundantly expressed in stromal infiltrating cells in all
      myxomas and occasionally in the endothelial cells. In the tumor stroma, the major
      source of MCP-1, TP and CCR-2 was macrophages, and the sites of positive staining
      for MCP-1, TP and CCR-2 matched in most of the myxomas. Statistical analysis
      revealed that the proportions of MCP-1-positive myxoma and stromal cells, and TP
      positive myxoma and stromal cells significantly correlated with increased
      microvessel count. The proportions of MCP-1-positive myxoma and stromal cells
      significantly correlated with the proportion of TP-positive stromal cells. The
      mean microvessel count in myxomas with both high tumor and high stromal MCP-1 or
      TP expression was significantly higher than that in myxomas with low tumor and
      low stromal MCP-1 or TP expression. Small tumors (< or =55 mm in diameter)
      exhibited high MCP-1 or TP expression, and the microvessel count in small tumors
      was significantly higher than in large myxomas. Although the difference was not
      significant, myxomas with both high tumor and high stromal MCP-1 expression had a
      higher macrophage count than other myxomas. These results indicate that in
      cardiac myxoma, MCP-1 and TP may be regarded as important angiogenic signals
      accompanying growth.

PMID- 12520154
TI  - Isolated post-challenge hyperglycemia in patients with normal fasting glucose
      concentration exaggerates neointimal hyperplasia after coronary stent
      implantation.
AB  - Postprandial hyperglycemia has been shown to increase the risk of cardiovascular
      disease as much as overt diabetes mellitus does. The aim of this study was to
      determine whether isolated post-challenge hyperglycemia during an oral glucose
      tolerance test (OGTT) is related to exaggerated neointimal proliferation after
      coronary stent implantation. Forty seven coronary lesions treated with stents in
      40 patients who had normal fasting glucose levels (<110 mg/dl) were categorized
      into the following 2 groups according to the results of a 75-g OGTT: 29 lesions
      in 24 patients with normal glucose tolerance (NGT group) and 18 lesions in 16
      patients with abnormal glucose tolerance (AGT group). Although there were no
      differences in angiographic characteristics before and immediately after stenting
      between the 2 groups, the minimal lumen diameter was significantly smaller
      (p=0.04) and the degree of stenosis and late loss were also significantly greater
      (p=0.01 and p=0.047) in the AGT group than in the NGT group at 6-month follow-up.
      Multiple regression analysis including the insulin concentrations during an OGTT
      revealed that the 120-min plasma glucose concentration after glucose load
      significantly correlated with late loss (p=0.0018) and the degree of stenosis
      (p=0.0100) at follow-up. It is concluded that isolated post-challenge
      hyperglycemia exaggerates neointimal hyperplasia after coronary stent
      implantation.

PMID- 12520155
TI  - Relationship between left atrial appendage function and left atrial thrombus in
      patients with nonvalvular chronic atrial fibrillation and atrial flutter.
AB  - The relationship between the left atrial appendage (LAA) function, as assessed by
      transesophageal echocardiography, and the incidence of left atrial thrombus was
      evaluated in 62 patients with nonvalvular chronic atrial fibrillation (AF; n=50)
      and atrial flutter (AFL; n=12). It was hypothesized that in both AF and AFL not
      only the LAA flow velocity (LAAFV), but also the frequency of the LAA movement
      (the LAA flow time, LAAFT) is a major contributing factor to thrombus formation.
      LAAFT was defined as the average duration of LAA flow with emptying and filling
      waves. The patients with AF were divided into 2 groups: lone AF (n=14) and non
      lone AF (n=36). LAA thrombus was found in 6 patients with none-lone AF. LAAFV was
      lower and LAAFT was shorter in patients with thrombus as compared with patients
      without thrombus (12.0+/-2.2 cm/s vs 24.1+/-10.6 cm/s, 68.7+/-1.5 ms vs 72.9+/
      3.3 ms, p<0.01, respectively). Patients with AFL had higher LAAFV and longer
      LAAFT than those with chronic AF. The present data suggest that, in addition to
      LAAFV, LAAFT characterized LAA function and might serve as a predictor of
      thrombus formation in chronic AF. With respect to LAA function, patients with
      lone AF or AFL are at low risk for thrombus formation.

PMID- 12520156
TI  - Effects of phase III cardiac rehabilitation programs on health-related quality of
      life in elderly patients with coronary artery disease: Juntendo Cardiac
      Rehabilitation Program (J-CARP).
AB  - The purpose of this prospective randomized controlled trial was to assess the
      impact of phase III comprehensive cardiac rehabilitation (CR) on health-related
      quality of life (HRQOL) in elderly patients with coronary artery disease (CAD).
      Thirty-eight elderly males (mean age, 70 years) with CAD were stratified as the
      intervention group (n=20) and the control group (n=18). In the intervention
      group, patients participated in CR for 6 months, whereas in the control group,
      they received standard care. Validated questionnaires were obtained to evaluate
      HRQOL using the Medical Outcome Study Short-Form 36 Health Status Survey (SF-36),
      State-trait anxiety inventory questionnaire (STAI) and Self-rating Depression
      Scale (SDS) at baseline and after 6 months. At baseline, scores of SF-36 except
      for general health, STAI and SDS were not different in either group. After 6
      months, in the intervention group, scores of bodily pain, general health,
      vitality and mental health of SF-36 improved significantly compared with
      baseline. State anxiety scores also improved significantly (p<0.01), but SDS
      depression scores were not improved. In the control group, none of the parameters
      significantly changed. These results indicate that elderly patients with CAD
      should be vigorously encouraged to pursue CR even in chronic phase III.

PMID- 12520157
TI  - Determinants of the development of mitral regurgitation in pacing-induced heart
      failure.
AB  - The pacing-induced heart failure model provides an opportunity to assess the
      structural and functional determinants of mitral regurgitation (MR) in dilated
      cardiomyopathy. This study aimed to evaluate MR to better understand the
      multitude of factors contributing to its development. Heart failure was induced
      by rapid ventricular pacing (230 beats/min) in 40 mongrel dogs. Left ventricular
      (LV) size and MR were evaluated echocardiographically. LV contractility was
      analyzed using a conductance catheter. MR increased to mild in 12 animals
      (regurgitant orifice area, 0.06+/-0.05 cm(2)), moderate in 15 (0.14+/-0.07
      cm(2)), and severe in 13 (0.34+/-0.16 cm(2)). The grade of MR had an inverse
      relationships with E(max) (the slope of the end-systolic pressure-volume
      relationship, p<0.01) and dE/dt (the slope of the maximum rate of change of
      pressure-end-diastolic volume [V(ED)] relationship, p<0.01) and positive
      relationships with V(ED) and end-diastolic cross-sectional areas and lengths
      (p<0.05) by univariate analysis. The dE/dt had an independently significant
      (p<0.01) relationship by multivariable logistic regression. Many factors
      influence the development of MR and because of its similarity to the clinical
      situation, this model can be used to investigate MR and heart failure, as well as
      new surgical therapies.

PMID- 12520158
TI  - Characteristic effects of alpha1-beta1,2-adrenergic blocking agent, carvedilol,
      on [Ca2+]i in ventricular myocytes compared with those of timolol and atenolol.
AB  - Beta-adrenergic stimulation and the resultant Ca(2+) load both seem to be
      associated with progression of heart failure as well as hypertrophy. Because the
      alpha(1)-, beta(1,2)-blocker, carvedilol, has been shown to be outstandingly
      beneficial in the treatment of heart failure, its direct effects on intracellular
      calcium ion concentration ([Ca(2+)](i)), including antagonism to isoproterenol,
      in ventricular myocytes were investigated and then compared with a selective
      beta(1)-blocker, atenolol, and a non-selective beta(1,2)-blocker, timolol. At 1
      300 nmol/L, carvedilol decreased the amplitude of [Ca(2+)] (i) by approximately
      20% independently of its concentration, which was a similar effect to timolol.
      All the beta-blockers at 10 nmol/L decreased the amount of cAMP, but atenolol had
      the least effect. Carvedilol in the micromol/L order further diminished the
      amplitude of [Ca(2+)](i) transients, and at 10 micromol/L increased the voltage
      threshold for pacing myocytes. These effects were not observed with timolol or
      atenolol. L-type Ca2+ currents (I(Ca)) were decreased by carvedilol in the
      micromol/L order in a concentration dependent manner. As for the beta
      antagonizing effect, the concentrations of carvedilol, timolol, and atenolol
      needed to prevent the effect of isoproterenol by 50% (IC(50)) were 1.32, 2.01,
      and 612 nmol/L, respectively. Furthermore, the antagonizing effect of carvedilol
      was dramatically sustained even after removal of the drug from the perfusate.
      Carvedilol exerts negative effects on [Ca(2+)](i), including inhibition of the
      intrinsic beta-activity, reduction of I(Ca) in the micromol/L order, and an
      increase in the threshold for pacing at > or =10 micromol/L. Data on the IC(50)
      for the isoproterenol effect suggest that carvedilol could effectively inhibit
      the [Ca(2+)](i) load induced by catecholamines under clinical conditions.

PMID- 12520159
TI  - Atrial blood cyst with ischemic heart disease.
AB  - A 52-year-old male with coronary artery disease had the extremely rare occurrence
      of a blood cyst in the right atrium. Surgical removal with coronary artery bypass
      grafting was performed successfully.

PMID- 12520160
TI  - Brugada syndrome with ventricular tachycardia and fibrillation related to
      hypokalemia.
AB  - A 60-year-old man with asymptomatic Brugada syndrome and neither a history of
      syncope nor family history of sudden death was admitted because of bronchial
      asthma. Serum potassium concentration was 3.8 mmol/L on admission, and decreased
      to 3.1 mmol/L on the 6th day, probably as a side effect of steroid therapy. The
      patient was found unconscious on the 7th day, and his serum potassium
      concentration was 3.4 mmol/L immediately after the episode. On the 8th day, the
      patient was again found unconscious, and polymorphic ventricular tachycardia and
      fibrillation (VT/VF) was documented on electrocardiographic (ECG) monitoring. The
      coved type of ST-segment elevation in leads V(1-3) was observed on the ECG after
      spontaneous recovery of sinus rhythm, and VT/VF associated with Brugada syndrome
      was diagnosed. The serum potassium concentration decreased to 2.9 mmol/L
      immediately after the episode, but QT prolongation was not observed during the
      clinical course. After the correcting the serum potassium concentration, there
      was no further recurrence of the malignant ventricular arrhythmia and syncope. An
      implantable cardioverter defibrillator was inserted to prevent sudden death.
      Hypokalemia that does not induce QT prolongation may contribute to the occurrence
      of VT/VF in Brugada syndrome.

PMID- 12520161
TI  - Acute pulmonary thromboembolism induced by prophylactic heparin use and a heparin
      coated catheter: a case of heparin-induced thrombocytopenia and thrombosis
      syndrome.
AB  - Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a potentially
      life-threatening side effect of heparin therapy, triggered by an immune response,
      and has been reported to be related not only to the therapeutic use of heparin
      but also to heparin-coated catheters. A 45-year-old woman with intrapelvic
      malignancy developed an acute pulmonary thromboembolism (PE) after hysterectomy
      despite prophylactic heparin use. Subsequent large doses of heparin for treatment
      of the PE exacerbated the thrombocytopenia and, moreover, a large thrombus formed
      around the heparin-coated central venous catheter. Anti-heparin-platelet factor 4
      complex antibody and heparin-induced platelet aggregation assay were positive, so
      the diagnosis was HITTS, and heparin was replaced by argatroban after carrying
      out thrombectomy. This therapy was successful, and the patient made favorable
      progress.

PMID- 12520162
TI  - Laparoscopy-assisted abdominal aortic aneurysm repair: first case reports from
      Japan.
AB  - Laparoscopy-assisted abdominal aortic aneurysm (AAA) repair consists of
      retroperitoneal laparoscopic dissection of the AAA and graft replacement
      performed via a mini-laparotomy. Two patients with infrarenal AAA underwent
      successful straight graft replacement using this hybrid approach. The
      retroperitoneal space was bluntly dissected under carbon dioxide
      pneumoretroperitoneum and further dissection was performed laparoscopically. This
      enabled proximal and distal control of the aneurysm, and occlusion of the lumbar
      arteries and the inferior mesenteric artery with hemoclips. A 7 cm mini
      laparotomy was sufficient for the straight graft replacement. Laparoscopy
      assisted repair is a less invasive technique for the treatment of AAA and can be
      regarded as the initial step towards totally endoscopic repair.

PMID- 12520163
TI  - Oxidized low-density lipoproteins: what is understood and what remains to be
      clarified.
AB  - Oxidized low-density lipoprotein (OxLDL) has previously been thought to promote
      atherogenesis through foam cell formation. However, the actual nature of OxLDL
      present in vivo remained obscure until recently. We have produced a monoclonal
      antibody, DLH3, which specifically binds to OxLDL but not to native LDL. The
      presence of OxLDL in the LDL fraction of human plasma was demonstrated by
      introducing a sandwich ELISA procedure using DLH3 together with an anti-apoB
      antibody. Furthermore, OxLDL levels appeared to increase in certain pathological
      conditions including acute myocardial infarction and carotid artery
      atherosclerosis. Accumulation of OxLDL in atherosclerotic lesions has also been
      demonstrated by immunohistochemical and biochemical studies using the DLH3
      antibody. This antibody recognizes oxidized phosphatidylcholines (OxPC) generated
      during oxidative modification of LDL, and OxPC-apoB adducts formed in OxLDL are
      the presumed antigens. Measuring OxLDL in plasma would be a useful diagnostic
      tool for cardiovascular diseases. However, there still remain some major
      questions related to OxLDL, the answers to which are crucial for understanding
      the mechanisms of atherogenesis.

PMID- 12520164
TI  - Cytotoxicity and apoptotic inducibility of Vitex agnus-castus fruit extract in
      cultured human normal and cancer cells and effect on growth.
AB  - A crude extract was prepared with ethanol from dried ripened Vitex agnus-castus
      fruits growing in Israel (Vitex extract). Cytotoxicity of the extract against
      human uterine cervical canal fibroblast (HCF), human embryo fibroblast (HE-21),
      ovarian cancer (MCF-7), cervical carcinoma (SKG-3a), breast carcinoma (SKOV-3),
      gastric signet ring carcinoma (KATO-III), colon carcinoma (COLO 201), and small
      cell lung carcinoma (Lu-134-A-H) cells was examined. After culture for 24 h
      (logarithmic growth phase) or 72 h (stationary growth phase), the cells were
      treated with various concentrations of Vitex extract. In both growth phases,
      higher growth activity of cells and more cytotoxic activity of Vitex extract were
      seen. The cytotoxic activity against stationary growth-phase cells was less than
      that against logarithmic growth-phase cells. DNA fragmentation of Vitex extract
      treated cells was seen in SKOV-3, KATO-III, COLO 201, and Lu-134-A-H cells. The
      DNA fragmentation in Vitex extract-treated KATO-III cells was inhibited by the
      presence of the antioxidative reagent pyrrolidine dithiocarbamate or N-acetyl-L
      cysteine (NAC). Western blotting analysis showed that in Vitex extract-treated
      KATO-III cells, the presence of NAC also inhibited the expression of heme
      oxygenase-1 and the active forms of caspases-3, -8 and -9. It is concluded that
      the cytotoxic activity of Vitex extract may be attributed to the effect on cell
      growth, that cell death occurs through apoptosis, and that this apoptotic cell
      death may be attributed to increased intracellular oxidation by Vitex extract
      treatment.

PMID- 12520165
TI  - Increase of intracellular glutathione by low-dose gamma-ray irradiation is
      mediated by transcription factor AP-1 in RAW 264.7 cells.
AB  - The mechanism of the elevation of intracellular glutathione induced by low-dose
      gamma-rays was examined in RAW 264.7 cells. The expression of mRNA for gamma
      glutamylcysteine synthetase (gamma-GCS) increased soon after gamma-ray (0.5 Gy)
      irradiation, and peaked between 3 h and 6 h post-irradiation. A dose of 0.25 to
      0.5 Gy was optimum for induction of gamma-GCS mRNA expression at 3 h post
      irradiation. The effect of inhibitors of activator protein-1 (AP-1) and nuclear
      factor kappaB (NF-kappaB) on the radiation-induced gamma-GCS gene expression was
      then examined. The induction of gamma-GCS mRNA expression was significantly
      suppressed when AP-1 DNA binding, but not NF-kappaB DNA binding, was inhibited.
      Finally, electrophoretic mobility shift assay showed that the low-dose radiation
      markedly increased the DNA binding of AP-1, but not NF-kappaB, soon after
      irradiation. These results suggest that the increase of glutathione levels in RAW
      264.7 cells by low-dose gamma-ray irradiation is mediated by transcriptional
      regulation of the gamma-GCS gene, predominantly through the AP-1 binding site in
      its promoter.

PMID- 12520166
TI  - Effects of sucralfate on gastric irritant-induced necrosis and apoptosis in
      cultured guinea pig gastric mucosal cells.
AB  - We previously reported that several gastric irritants, including ethanol,
      hydrogen peroxide, and hydrochloric acid, induced both necrosis and apoptosis in
      cultured gastric mucosal cells. In the present study, we examined the effects of
      sucralfate, a unique gastroprotective drug, on gastric irritant-induced necrosis
      and apoptosis produced in vitro. Sucralfate strongly inhibited ethanol-induced
      necrosis in primary cultures of guinea pig gastric mucosal cells. The
      preincubation of cells with sucralfate was not necessary for its cytoprotective
      effect to be observed, thus making its mechanism of action different from that of
      other gastroprotective drugs. Necrosis of gastric mucosal cells induced by
      hydrogen peroxide or indomethacin was also suppressed by sucralfate. On the other
      hand, sucralfate only weakly inhibited ethanol-induced apoptosis. These results
      suggest that the cytoprotective effect of sucralfate on gastric mucosa in vivo
      can be explained, at least in part, by its inhibitory effect on gastric irritant
      induced necrosis.

PMID- 12520167
TI  - Okadaic acid decreases the leptin content in isolated mouse fat pads.
AB  - Okadaic acid (OA) decreased the leptin content in isolated mouse fat pads in a
      time and dose-dependent manner. MG-132, a membrane-permeable proteasome
      inhibitor, prevented the decrease by OA, suggesting the involvement of proteasome
      in the OA action. No significant decrease in the incorporation of [(3)H]leucine
      into leptin was observed with a 4-h incubation, although the amino acid
      incorporation was stimulated by insulin and decreased by cycloheximide. These
      results suggest that the OA action is independent of the decrease in protein
      synthesis. The proteasome fraction, which had been separated from the fat pads
      pretreated with OA, enhanced the proteolytic degradation of exogenous
      [(125)I]leptin in the presence of an ATP-regenerating system together with an
      ubiquitination system. No enhancement of hydrolytic activity against Suc-Leu-Leu
      Val-Tyr-AMC was detected in the OA-treated proteasome fraction, suggesting that
      the activation of proteasome is not involved in the OA action. The OA-treated
      proteasome fraction had decreased phosphatase activity against p-nitrophenyl
      phosphate, suggesting that OA entering the cells may exert its action by
      preventing dephosphorylation of key molecules. OA may reduce the intracellular
      leptin content through the increased ubiquitination and proteolytic turnover of
      leptin by the proteasome, based on the decreased phosphatase activity.

PMID- 12520168
TI  - Analysis of cell cycle gene expression responding to acetoxyscirpendiol isolated
      from Paecilomyces tenuipes.
AB  - Paecilomyces tenuipes is believed to contain potential oncostatic and tumor
      reducing components. Molecular mechanism, however, is poorly understood
      concerning the potential antitumor components and their biological function. We
      purified acetoxyscirpendiol (ASD) from methanolic extracts (MPT) of the fungus
      and tested the two compounds for the molecular profile of their antitumor
      potential. Using a differential display protocol, cyclin C and Mad-1 were
      identified as candidate genes responding to MPT. When a quantitative PCR was
      performed on the total RNA from MCF-7 treated by MPT or ASD, gene expressions of
      cyclin C and Mad-1 were greatly augmented. In terms of protein expression, cyclin
      C level increased up to 12 folds in response to ASD as well as MPT. Similar as
      MPT treatments, ASD-treated cells synthesize cyclin C as 2-4 fold compared to the
      control treatments. In terms of Mad-1 expression in cells treated with ASD, the
      level of Mad-1 expression increased up to 2.5 folds by MPT treatment. Cyclin C
      expression was compared with non-treated cells in various cell lines. MCF-7 cell
      was shown highly responsive to the MPT or ASD treatment. Taken together, these
      results strongly indicate that MPT contains potential antitumor components which
      might exert their action by modulating cell cycle-related genes such as cyclin C
      and Mad-1 in MCF-7. The major antioncogenic component in MPT may be ASD which
      modulates cyclin C and Mad-1 expression.

PMID- 12520169
TI  - Effect of Puerariae radix on c-Fos expression in hippocampus of alcohol
      intoxicated juvenile rats.
AB  - Alcohol consumption is known to cause substantial neuronal loss in several
      regions of the brain. In Oriental medicine, medications based on Puerariae radix
      have been known to be of efficacy in the treatment of alcohol-related problems.
      In the present study, the effect of the aqueous extract of Puerariae radix on the
      expression of c-Fos, an immediate early gene whose expression is sometimes used
      as a marker for stimulus-induced changes in the metabolic activity of neurons, in
      the hippocampus of acutely alcohol-intoxicated juvenile rats was investigated via
      immunohistochemistry. In the first part of the experiment, Sprague-Dawley rats
      were divided into six groups: the control group, the alcohol-treated group, the
      alcohol- and 0.3 mg/kg Puerariae radix-treated group, the alcohol- and 3 mg/kg
      Puerariae radix-treated group, the alcohol- and 30 mg/kg Puerariae radix-treated
      group, and the alcohol- and 300 mg/kg Puerariae radix-treated group. In the
      second part of the experiment, animals were divided into four groups: the control
      group, the 30 mg/kg Puerariae radix-treated group, the alcohol-treated group, and
      the alcohol- and 30 mg/kg Puerariae radix-treated group. From the results, it was
      demonstrated that alcohol administration significantly decreases the number of
      Fos-positive cells in the various regions of the hippocampus, and Puerariae radix
      treatment inhibits the alcohol-induced suppression of the expression of Fos in
      the hippocampus in a dose-dependent manner. Puerariae radix exerted no
      significant effect on Fos expression in the hippocampus of normal rats. The
      results presented in this study suggest that Puerariae radix may alleviate
      alcohol-induced disruption of hippocampal functions.

PMID- 12520170
TI  - Hypotensive activity and toxicology of constituents from Bombax ceiba stem bark.
AB  - A novel constituent, shamimicin, 1"', 1"""'-bis-2-(3,4-dihydroxyphenyl)-3,4
      dihydro-3,7-dihydroxy-5-O-xylopyranosyloxy-2H-1-benzopyran along with lupeol,
      which possesses potent hypotensive activity, has been isolated from Bombax ceiba
      stem bark. BCBMM--one of the most active hypotensive fractions has revealed its
      adverse effects on heart, liver and kidneys of mice at the dose of 1000 mg/kg/d.

PMID- 12520171
TI  - Induction of triglyceride accumulation in the liver of rats by perfluorinated
      fatty acids with different carbon chain lengths: comparison with induction of
      peroxisomal beta-oxidation.
AB  - The potency to accumulate triglyceride (TG) was compared between perfluorinated
      fatty acids (PFCAs) with different carbon chain lengths in the liver of male and
      female rats and induction of peroxisomal beta-oxidation. In male rats, either
      perfluoroheptanoic acid (C7) or perfluorooctanoic acid (C8) had no effect,
      although perfluorononanonic acid (C9) and perfluorodecanoic acid (C10) markedly
      accumulated TG. In female rats, C7, C8, and C9 did not cause TG accumulation,
      whereas C10 caused TG accumulation at the same level as in male rats. TG
      accumulation induced by C9 was regulated by the level of testosterone in male
      rats. In contrast with TG accumulation, peroxisomal beta-oxidation was induced by
      C8, C9, and C10 in male rats and by C9 and C10 in female rats. Only a slight
      difference was observed in the induction by C9 between male and female rats. The
      induction of TG accumulation by these PFCAs occurred in a dose-dependent manner
      and significantly correlated with hepatic concentrations of PFCA regardless of
      their carbon chain length, as was observed with induction of peroxisomal beta
      oxidation. There is, however, a striking difference in the hepatic concentration
      of PFCA required to cause induction of TG accumulation and that of peroxisomal
      beta-oxidation. The concentration of PFCA required to induce TG accumulation is
      much higher than that to induce peroxisomal beta-oxidation. These results
      strongly suggest that TG accumulation induced by PFCAs, as well as the induction
      of peroxisomal beta-oxidation, is dependent only on the number of PFCA molecules
      in hepatocytes, but is not due to the difference in their chemical structures,
      and that there is a marked difference in the PFCA threshold to cause distinct
      biological effects.

PMID- 12520172
TI  - Total coenzyme Q10 concentrations in Asian men following multiple oral 50-mg
      doses administered as coenzyme Q10 sustained release tablets or regular tablets.
AB  - Coenzyme Q(10) (CoQ(10)), a highly lipophilic compound present in the inner
      mitochondrial membrane, is essential for production of cellular energy in the
      form of ATP. CoQ(10) is used as a dietary supplement and for treatment of various
      cardiovascular disorders. Our goal was to compare the CoQ(10) levels in Asians
      following multiple oral doses administered as sustained release or regular
      tablets. Twenty healthy male volunteers (19-23 years old) were divided into two
      equal groups. Each subject in Group I received 50 mg oral doses of coenzyme Q(10)
      as sustained release tablets once a day for fifteen days, while subject in Group
      II received 50 mg doses of coenzyme Q(10) regular tablets. The CoQ(10) levels
      were measured by HPLC-UV (reverse phase ODS column, 10 microm, 250 x 4.6 mm; oven
      temperature 30 degrees C). Mobile phase was constituted by methanol-ethanol 9 : 1
      v/v. Flow rate was 1.5 ml/min and UV detection was carried out at 275 nm.
      Coenzyme Q(9) was used as an internal standard. CoQ(10) baseline in the morning
      was 0.88+/-0.48 mg/l. Following 1 week 50 mg/d dosing of CoQ(10), plasma CoQ(10)
      concentrations increased to 1.85+/-1.03 mg/l for sustained release tablets and up
      to 1.37+/-0.74mg/l for regular tablets. The net increment proportion in AUC for
      sustained release and regular tablets were 148.26+/-176.56%, 102.57+/-130.00%,
      respectively. Both preparations significantly increased the systemic exposure
      when compared to endogenous baseline.

PMID- 12520173
TI  - Saiko-ka-Ryukotsu-Borei-To inhibits intimal thickening in carotid artery after
      balloon endothelial denudation in cholesterol-fed rats.
AB  - Oral administration of Saiko-ka-Ryukotsu-Borei-To (SRB), a traditional Chinese
      formulation, dose dependently inhibited intimal thickening in carotid artery
      injured by balloon endothelial denudation in cholesterol-fed rats. SRB also
      inhibited vascular smooth muscle cell (VSMC) proliferation, which is assessed by
      counting the VSMCs immunoreactive with antiproliferating cell nuclear antigen
      (PCNA) antibody in the intimal area. VSMC proliferation is considered to play a
      central role in the development of intimal thickening. SRB slightly, but not
      significantly, reduced serum total cholesterol and low-density lipoprotein
      cholesterol. These results indicate that the suppressive effect of SRB on intimal
      thickening may result from its inhibitory effect against VSMC proliferation, but
      does not depend on lowering of lipid levels. The balloon injury model used in
      this study has similar pathological processes to restenosis after percutaneous
      coronary intervention (PCI). Therefore the present results may provide a new
      therapeutic strategy using SRB to reduce restenosis after PCI in the treatment of
      patients with ischemic coronary artery disease. Furthermore, since it is
      considered that artery restenosis after balloon injury in PCI is "accelerated
      atherosclerosis, " SRB may have beneficial effects in atherosclerosis that
      develops over a long clinical course in hyperlipidemia, diabetes, etc.

PMID- 12520174
TI  - Inhibitors of nitric oxide production from hops (Humulus lupulus L.).
AB  - Nitric oxide (NO) plays an important role in many inflammatory responses and is
      also involved in carcinogenesis. In the present study, we investigated the
      inhibitory effect of extracts from Humulus lupulus L. on both the production of
      NO and the expression of inducible NO synthase (iNOS) in mouse macrophage RAW
      264.7 cells. The production of NO was induced by a combination of
      lipopolysaccharide (LPS) and IFN-gamma, and determined by Griess assay. The
      expression of iNOS was detected by Western blotting. The LPS/IFN-gamma-induced
      production of NO and expression of iNOS were significantly inhibited by the ethyl
      acetate soluble fraction of Humulus lupulus L. Through bioactivity guided
      fractionation, humulene, five chalcones, 2,2-di-(3-methyl-2-butyleyl)-4,5
      dihydoxy-cyclopent-4-en-1,3-dione, lupulone and three of its derivatives were
      isolated from the ethyl acetate soluble fraction. The chalcones, including
      xanthohumol, significantly inhibited the production of NO by suppressing the
      expression of iNOS.

PMID- 12520175
TI  - Examination of the mechanism of oleic acid-induced percutaneous penetration
      enhancement: an ultrastructural study.
AB  - The epidermal permeability barrier appears to be regulated primarily by the
      lamellar arrangement of lipid bilayers between coneocytes of the stratum corneum
      and presents a significant barrier to the transdermal delivery of drugs. The aim
      of the present study was to investigate the effects of oleic acid on the
      ultrastructure of stratum corneum lipids in rat skin. Wistar rats were treated
      topically with 10% oleic acid/propylene glycol for 2 h, the structure of stratum
      corneum was examined by electron microscopy using osmium tetroxide or ruthenium
      tetroxide postfixation, and the epidermal barrier function was evaluated in a
      lanthanum tracer study. Ultrastructural examination revealed that there was a
      marked alteration in the stratum corneum and the tracer penetrated into the
      intercellular spaces of the stratum corneum after application of oleic acid.
      These results suggest that ruthenium tetroxide postfixation is a powerful tool
      for the study of the stratum corneum lipid structure. Oleic acid might increase
      the epidermal permeability through a mechanism involving the perturbation of
      stratum corneum lipid bilayers and lacunae formation to enhance transdermal drug
      delivery.

PMID- 12520176
TI  - Drug delivery to the eye with a transdermal therapeutic system.
AB  - A matrix-type transdermal therapeutic system was developed for treating diseases
      of the eye where it is difficult for drug molecules to reach with conventional
      topical instillation. Prednisolone was employed as a model drug. An in vivo study
      using rats showed that the daily application of the patch maintained a constant
      plasma concentration of the drug, which was equivalent the therapeutic plasma
      level following three times daily oral administration (30 mg), for approximately
      24 h. Transdermal delivery provided equivalent to or higher bioavailability (drug
      distribution) to the eyeball of topical administration. Moreover, pharmacokinetic
      analysis indicated that the present transdermal therapeutic system may be
      clinically effective as a new treatment for ocular diseases.

PMID- 12520177
TI  - Inhibitory effect of acyl-CoA:cholesterol acyltransferase inhibitor-low density
      lipoprotein complex on experimental atherosclerosis.
AB  - KV-2920 is a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor. To
      confirm the efficacy of KV-2920-low density lipoprotein (LDL) complex (KV-LDL
      complex) as a drug-carrier complex on experimental atherosclerosis, we examined
      its inhibitory effects in vitro and in vivo. LDL was isolated from human plasma
      and the KV-LDL complex was prepared by incubation in the presence of Celite 545.
      The complex contained about 800 mol KV-2920 in 1 mol LDL. The cholesterol levels
      in the serum and aorta of atherogenic mice after 14 weeks of feeding were
      significantly higher than those of nonatherogenic mice. With the intravenous
      injection of KV-LDL complex, although the cholesterol levels in the serum were
      not influenced, the level of cholesterol ester in the aorta of atherogenic mice
      was significantly reduced. The concentration of cholesterol ester in the
      macrophages derived from ICR mice was predominantly increased by incubation with
      LDL for 48 h, this increase was significantly inhibited by incubation with KV-LDL
      complex. Moreover, the complex also inhibited the increase of cholesterol ester
      in macrophages following incubation with oxidized LDL. These findings suggest
      that KV-LDL complex inhibits the foam cell formation of macrophages though action
      of KV-2920 as an ACAT inhibitor, and prevents the accumulation of cholesterol
      ester in the aorta of atherogenic mice. Therefore, KV-LDL complex may be useful
      as a drug-carrier complex in antiatherosclerotic therapy.

PMID- 12520178
TI  - Urinary pharmacokinetics of baicalein, wogonin and their glycosides after oral
      administration of Scutellariae Radix in humans.
AB  - Baicalin, baicalein, wogonoside and wogonin are flavone constituents of
      Scutellariae Radix with various beneficial biological activities. The purpose of
      this study was to investigate the urinary pharmacokinetics of these flavones
      after oral administration of Scutellariae Radix commercial powder. Ten healthy
      male volunteers received a dose of 5.2 g commercial powder (comparable to 9 g
      crude drug), respectively. The concentrations of baicalin, baicalein and wogonin
      in the commercial powder as well as their metabolites in urine were assayed by
      HPLC method. The glucuronides and sulfates of baicalein and wogonin in urine were
      hydrolyzed with beta-glucuronidase and sulfatase, respectively. Our results
      showed that the mean cumulated renal excretion of baicalein glucuronides and
      sulfates were 43.1+/-4.5 micromol (2.9% of dose) and 64.8+/-6.3 micromol (4.3% of
      dose), respectively, whereas wogonin glucuronides and sulfates were 21.6+/-2.0
      micromol (5.9% of dose) and 20.7+/-1.7 micromol (5.7% of dose), respectively. The
      result indicated that the renal excretion of conjugated metabolites of wogonin
      (11.6% of dose) were higher than that of baicalein (7.2% of dose). The baicalein
      sulfates was predominant than the corresponding glucuronides, whereas wogonin
      sulfates was comparable to the corresponding glucuronides.

PMID- 12520179
TI  - Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps
      sinensis.
AB  - This study was conducted to investigate the hypocholesterolemic effect of the hot
      water fraction (HW) from cultured mycelia of Cordyceps sinensis in a 5 l
      fermenter. The composition of HW was mainly carbohydrate (83.9%) and protein
      (11.8%) on a dry basis, and the carbohydrate of HW consisted of glucose, mannose,
      galactose, and arabinose in the molecular ratio of 1.0 : 0.8 : 0.5 : 0.1,
      respectively. In mice fed a cholesterol-free diet and those fed a cholesterol
      enriched diet, body and liver weights were not significantly different from those
      of the controls. The serum total cholesterol (TC) of all mice groups administered
      HW (150 and 300 mg/kg/d, respectively) with the cholesterol-enriched diet
      decreased more than in the control group. Among the mice fed the cholesterol
      enriched diet, HW also increased the high-density lipoprotein (HDL) cholesterol
      level, but decreased the very low-density lipoprotein plus low-density
      lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL- and VLDL+LDL
      cholesterol levels consequently decreased the atherogenic value. The results
      indicate that HW in rats administered a cholesterol-enriched diet decreased the
      plasma cholesterol level. The 300 mg/kg dose had a significant effect on the
      serum TC level.

PMID- 12520180
TI  - Modulation of vacuolar H+ -pumps and aquaporin by phytohormones in rice seedling
      leaf sheaths.
AB  - The effects of exogenously applied gibberellic acid (GA(3)) or brassinolide (BL)
      on the H(+)-pumps and aquaporin in the vacuolar membrane of rice seedling leaf
      sheath were investigated. Antibodies against mung bean H(+)-PPase, the B subunit
      of V-ATPase, and radish tonoplast intrinsic protein (TIP) cross-reacted with the
      vacuolar membrane proteins of rice seedling leaf sheath. The results of
      immunoblot analysis showed that the amounts of H(+)-PPase and V-ATPase were
      retained at a high level for two days in the presence of GA(3), although the
      level gradually decreased without phytohormones, indicating that GA(3) has a
      promotive effect on the activities of vacuolar H(+)-pumps. However, the levels of
      V-ATPase and H(+)-PPase were increased on day 2 and then decreased when treated
      with BL. There were no visible differences in the level of TIP upon treatment
      with GA(3) and BL. In comparison with the water control, the activity of H(+)
      PPase treated with BL was also retained at a relatively high level, suggesting
      that BL has a stimulative effect on the activities of H(+)-PPase. These results
      indicate that GA(3) and BL might be involved in the regulation of the quantity
      and activities of plant vacuolar H(+)-pumps.

PMID- 12520181
TI  - Peroxisome proliferative drugs do not induce an increase of rat mevalonate
      pyrophosphate decarboxylase.
AB  - To determine whether or not the expression of mevalonate pyrophosphate
      decarboxylase (MPD) depends on the proliferation of peroxisomes, we examined
      change in the protein level of MPD in the crude extract, the cytosol and the
      peroxisome-enriched fraction of the livers of rats administered peroxisome
      proliferative drugs. No increase of MPD was observed in any of these fractions.
      These data suggest that the expression of MPD is independent of the proliferation
      of peroxisomes and may be maintained via a specific regulatory mechanism
      different from that of the expression of peroxisome proliferator-activated
      receptor alpha.

PMID- 12520182
TI  - Apoptosis-inducing effect of a new bisphosphonate, YM529, on various
      hematopoietic tumor cell lines.
AB  - In recent years, it has been reported that bisphosphonates inhibited the cell
      cycle of myeloma cells to inhibit cell proliferation directly, and it was also
      reported that bisphosphonates induced apoptosis of myeloma cells in vitro.
      Recently, YM529 was developed as a new third-generation bisphosphonate. In our
      experiment, we investigated whether YM529 showed an antitumor effect on
      hematopoietic tumor cell lines other than myeloma, and we compared YM529 with
      YM175, which had a relatively more potent antitumor effect than that of existing
      bisphosphonates. We found that YM529 inhibited cell proliferation in various
      hematopoietic tumor cell lines (acute promyelocytic leukemia cell line HL-60,
      chronic myeloid leukemia cell line K562, histiocytic lymphoma cell line U937,
      lymphoblastic leukemia T cell line Jurkat, acute lymphoblastic leukemia T cell
      line MOLT-4, lymphoblastic leukemia B cell line CCRF-SB) including myeloma
      (myeloma cell line HS-Sultan) dose-dependently and time-dependently to a degree
      equivalent or superior to that in myeloma, and induced apoptosis at a lower
      concentration as compared with YM175. We confirmed many dead cells as well as
      apoptosis based on the detection of the nuclei with separate globular structure,
      the activation of caspase-3, and the decrease in mitochondrial transmembrane
      potential. Therefore, it is concluded that further utilization of YM529 can be
      expected against hematopoietic tumor cells in the future.

PMID- 12520183
TI  - Some gastrointestinal function regulatory Kampo medicines have modulatory effects
      on human plasma adrenocorticotropic hormone and cortisol levels with continual
      stress exposure.
AB  - Rikkunshi-to, a gastrointestinal function regulatory traditional Chinese herbal
      (Kampo) medicine, has recently been evaluated for its clinical usefulness in
      stress and depression. This medicine has modulatory effects on the hypothalamo
      pituitary-adrenal axis and autonomic nervous function. We examined the effect of
      Rikkunshi-to and the other gastrointestinal function regulatory Kampo medicines,
      Hange-shashin-to, Hange-koboku-to, and Ninjin-to, on the plasma levels of
      adrenocorticotropic hormone (ACTH) and cortisol under stress conditions by
      repetitive blood sampling. Rikkunshi-to, Hange-shashin-to, and Hange-koboku-to
      significantly suppressed increases in plasma ACTH-immunoreactive substance (IS)
      levels compared with the response to a placebo. Rikkunshi-to and Hange-shashin-to
      significantly suppressed increases in plasma cortisol levels compared with the
      response to placebo. Ninjin-to had no significant effect on plasma ACTH-IS and
      cortisol levels. In this study, Rikkunshi-to, Hange-shashin-to, and Hange-koboku
      to (partially) regulated plasma ACTH and cortisol levels under stress. These
      modulatory effects might be beneficial in stress-related disease and suggest that
      these medicines have clinical pharmacologic activity.

PMID- 12520184
TI  - Leptin inhibits food intake without affecting brain NOx levels in food-deprived
      mice.
AB  - Effects of leptin on food intake and nitric oxide (NO) metabolites (nitrite and
      nitrate, NOx) levels of brain were investigated in mice. Leptin dose-dependently
      decreased milk intake in food-deprived mice. Administration of leptin at a dose
      of 1 mg/kg, which induces an apparent hypophagia, did not affect NOx levels in
      the hypothalamus and frontal cortex. These results suggest that leptin reduces
      food intake in food-deprived mice without altering NO production in the
      hypothalamus, which plays an important role in regulation of feeding.

PMID- 12520185
TI  - Anti-Sindbis activity of flavanones hesperetin and naringenin.
AB  - The effect of hesperetin, naringenin and its glycoside form on the Sindbis
      neurovirulent strain (NSV) replication in vitro was studied. All flavanones
      tested were not cytotoxic on Baby Hamster cells 21 clone 15 (BHK-21). Antiviral
      effect was evaluated by a colorimetric assay using MTT (3-(4,5 dimethylthiazol-2
      yl)-2,5-dipheyl-tetrazolium bromide) and by plaque reduction assay. Hesperetin
      and naringenin had inhibitory activity on NSV infection. The 50% inhibitory doses
      (ID(50%)) of both compounds were 20.5 and 14.9 microg/ml respectively, as
      established by plaque assay. However their glycosides, hesperidin and naringin
      did not have inhibitory activity. Implying that the presence of rutinose moiety
      of flavanones blocks the antiviral effect. Oxygenation on the 3' positions at the
      B rings on the hesperetin skeleton decrease the anti viral activity at 25
      microg/ml.

PMID- 12520186
TI  - Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis
      model.
AB  - The effects of berberine in senescence accelerated mice P6 (SAMP6) were
      investigated to learn whether the alkaloid affects bone mineral density (BMD).
      Oral administration of berberine (10 mg/kg/d) to male and female mice for 22
      weeks resulted in an increase in BMD in both sexes. A decreased concentration of
      deoxypyridinoline (Dpd) in urine was only observed in female mice. There was no
      effect on body or tibia weight or on the concentration of procollagen type I
      carboxyterminal extension peptide (PICP) in serum.

PMID- 12520187
TI  - Relaxation of uterine and aortic smooth muscle by glaucolides D and E from
      Vernonia liatroides.
AB  - Vernonia spp. (Asteraceae) are used in herbolaria in Latin America in menstrual
      and stomach disorders, suggesting smooth muscle relaxing properties of some of
      their chemical constituents. For pharmacological support for this belief,
      sesquiterpene lactones glaucolides D and E were assayed on isolated rat smooth
      muscle. Glaucolide E proved more potent than glaucolide D to relax high KCl- or
      noradrenaline-induced contractions in aorta and to relax the high KCl-contraction
      in uterus. Hirsutinolide-type sesquiterpene lactone also was tested but displayed
      no effect. Relaxation of smooth muscle by structurally related sesquiterpene
      lactone parthenolide has been attributed mainly to the alpha-methylene gamma
      lactone moiety; because glaucolides D and E lack this functional group, their
      relaxant properties may rely on other alkylating sites such as C10 of the
      germacra-1(10),4-diene-4-epoxide skeleton.

PMID- 12520188
TI  - Antitumor properties of irinotecan-containing nanoparticles prepared using
      poly(DL-lactic acid) and poly(ethylene glycol)-block-poly(propylene glycol)-block
      poly(ethylene glycol).
AB  - Irinotecan-containing nanoparticles (NP) were prepared by coprecipitation with
      addition of water to acetone solution of poly(DL-lactic acid), poly(ethylene
      glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) and irinotecan,
      and subsequent evaporation of organic solvent. NP were purified by gel filtration
      and used for experiments after condensation by evaporation. The obtained NP
      showed the drug content of 4.5% (w/w) and the mean particle diameter of 118 nm
      with the particle diameter distribution between 80-210 nm. When the antitumor
      effect was examined at a repeated dose of 20 mg irinotecan eq/kg for 3 d (3 x 20
      mg/kg) using mice bearing Sarcoma 180 subcutaneously, only NP suppressed tumor
      growth significantly. After i.v. injection in rats, NP maintained irinotecan
      plasma concentration longer than CPT-11 aqueous solution. The present
      nanoparticle formation is suggested as a possibly useful dosage form of
      irinotecan against solid tumor.

PMID- 12520189
TI  - Effects of various storage conditions and alterations of antioxidant contents on
      chromatic aberration of hydroquinone ointment.
AB  - Ointments of the skin depigmentation agent hydroquinone (HQ) have been prepared
      by extemporaneous nonsterile compounding in our hospital. The HQ ointments were
      highly effective in the treatment of various types of skin pigmentations;
      however, various problems have emerged including chromatic aberration of the
      ointments, a relatively large variability of efficacy, and mild side effects.
      Chromatic aberration is expected to induce non-compliance, and this may be the
      reason for the relatively large variability in efficacy. In this paper, the
      effects of various storage conditions on the chromatic aberration and HQ content
      of HQ ointments were evaluated, and it was suggested that the chromatic
      aberration was accelerated by exposure to high temperature, air and light,
      although these had no effect on the HQ content. In addition, various types of HQ
      ointments were prepared to find a formulation to minimize chromatic aberration,
      and it was found that the concentrations of antioxidants, Na(2)SO(3) and L(+)
      ascorbic acid (AsA), seemed to be too high, and that the protective effect of AsA
      on chromatic aberration was mainly due to its acidifying effect.

PMID- 12520190
TI  - Effects of alpha 1-acid glycoprotein on erythrocyte deformability and membrane
      stabilization.
AB  - The effects of alpha(1)-acid glycoprotein (AGP) on human erythrocyte membrane
      were examined in vitro. Bovine and dog AGP, in addition to human AGP or asialo
      human AGP were used, and the collected data were compared with that for human
      serum albumin (HSA). A new technique developed by Kikuchi was used to investigate
      erythrocyte deformability. The addition of AGPs including human AGP facilitated
      the passage of human erythrocytes with an average diameter of 7.2 microm
      suspended in phosphate buffered saline (PBS) through a 5 microm wide
      microchannel; hemolysis was suppressed after the passage. The stabilizing effects
      of AGPs on membrane were evaluated. Human AGP prevented hemolysis induced by
      hypotonic phosphate buffer solution. The effects of human AGP on the oxidative
      changes in erythrocytes exposed to oxygen radicals were investigated. Human AGP
      protected erythrocytes from H(2)O(2) and prevented the oxidation of
      dihydrorhodamine 123 to rhodamine 123 from H(2)O(2). We propose that the
      antioxidant activity of human AGP is due to the binding of free radicals. In all
      studies, the effects of human AGP on erythrocytes might not be a function of the
      negative charge associated with sialyl residues, because the presence of N
      acetylneuraminic acid had no effect. However, human AGP may promote
      microcirculation and antioxidant activity compared with HSA. No species
      differences in the physiological function of AGP were found. These results
      suggest that an increase in the AGP content of serum above the normal value found
      under pathological conditions facilitates the passage of erythrocytes through
      capillaries, stabilizes erythrocyte membranes and protects against oxidative
      stress, all of which are favorable for microcirculation.

PMID- 12520191
TI  - Specific methylation status of the entire CpG island is not a prerequisite for
      the formation of an inactive chromatin at the promoter region in cancer cells.
AB  - It is well-recognized that DNA methylation causes gene silencing. However,
      although DNA methylation is closely associated with alterations in chromatin
      structure, it is not clear whether methylation at a particular locus contributes
      to the formation of an inactive chromatin structure. In this study, we have
      investigated the chromatin structure of the CpG island of the human CDH1 gene in
      cancer cells. The CDH1-CpG island was differentially methylated between silenced
      cells, however, DNase I hypersensitive site that are present in the expressing
      cell were commonly lost in silenced cells and transcription factors were excluded
      from their binding sites. These results demonstrate that formation of an inactive
      structure was not affected by heterogeneous methylation status of the CpG island.

PMID- 12520192
TI  - [Is the care of drug users infected with hepatitis C virus effective?].

PMID- 12520193
TI  - [Does a living donor have a freedom choice?].

PMID- 12520194
TI  - [Adult living donor liver transplantation: why and how?].

PMID- 12520195
TI  - [Adult living donor liver transplantation: why the scepticism?].

PMID- 12520196
TI  - [Hepatitis C virus screening in drug users in an addiction out-patient unit].
AB  - AIM: To investigate the feasibility and efficacy of hepatitis C virus screening
      in drug users in an addiction out-patient unit. PATIENTS AND METHODS: All
      patients followed in an addiction out-patient unit were asked to undergo anti
      hepatitis C virus antibody testing; further evaluation and treatment if
      indicated, were offered to positive patients. When treatment was initiated
      (Metavir score >=F2), patients were followed-up both by the hepatologist and the
      out-patient unit physician. RESULTS: Between July 1997 and September 2000, 404
      consecutive patients (310 men, mean age: 32, alcohol intake >=50 g per day in
      51%, 94% in opiate substitution program) were included. Sixty-six per cent
      (269/404) of patients agreed to undergo HCV antibodies testing: 84% had a
      positive test. 68% of these patients accepted ALT serum measurement and 120 had
      indications for liver biopsy. Eighty-eight liver biopsies were performed, showing
      severe fibrosis (Metavir score F3 or F4) in 20 cases (22%). Ethanol intake was
      significantly correlated to fibrosis (P<0.05). Antiviral treatment was indicated
      in 47 patients but was only initiated in 27 due to patient refusal (n=7) or
      contraindication (n=13). Treatment had to be discontinued in 12 cases because of
      psychiatric side effects (depression: n=3; delirium: n=3; severe irritability:
      n=3; relapse with heroin injection: n=3). Finally, only 5 patients were sustained
      responders. CONCLUSION: Despite the high seroprevalence of HCV antibodies in this
      unit, the benefits of antiviral therapy are low due to high drop out rate.
      Ethanol withdrawal should be the highest priority in these patients.

PMID- 12520198
TI  - [Hirschsprung's disease: and then three loci].

PMID- 12520197
TI  - [Polycystic liver disease and its main complications].

PMID- 12520199
TI  - [Increased expression of HOXA9 gene in Hirschsprung disease].
AB  - OBJECTIVE: Hirschsprung disease is characterized by segmental aganglionosis of
      the terminal bowel. Neurons of the enteric nervous system arise from neural
      crest, migrate and colonize intestinal muscle coat where they proliferate and
      differentiate. The first pathophysiologic hypothesis suggests an absence of
      neural cell migration. The most recent hypothesis involves disorders of their
      homing and/or their differentiation due to an altered intestinal
      microenvironment. PATIENTS AND METHODS: We analyzed the expression of muscle
      markers and laminin isoforms by immunocytochemistry and of homeotic genes
      involved in the regionalization of the intestinal mesenchyme during development
      (HOXA4, HOXA9, HOXD9) by RT-PCR, in colon specimens from two children with
      Hirschsprung disease (pathological and transition regions) and from healthy adult
      controls. RESULTS: We showed an increase in HOXA9 gene expression in Hirschsprung
      disease specimens while HOXA4 and HOXD9 mRNA expressions were unchanged. No
      significant differences in the muscle markers nor in the laminin isoforms were
      noted. CONCLUSION: These data suggest that intrinsic dysregulation of the
      intestinal wall microenvironment could account for the pathophysiology of
      Hirschsprung disease.

PMID- 12520200
TI  - Prevalence of irritable bowel syndrome in the French population according to the
      Rome I criteria.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastro
      intestinal disease. In the absence of specific markers, definition and hence
      diagnosis depend on clinical presentation. Of the various attempts to set
      criteria for IBS, the most recent are Rome I and Rome II classifications. AIMS:
      To estimate in a general population the prevalence of IBS using the modified Rome
      I criteria, and to investigate socio-demographic criteria, symptoms and
      management. METHODS: A total of 11,131 people aged 18 years and over,
      representative of the French population, were surveyed. A diagnostic
      questionnaire based on the modified Rome I criteria was used to identify IBS
      sufferers, who were then questioned further about the symptoms and medical
      management of their IBS. RESULTS: Of the 5,299 men and 5,832 women interviewed,
      445 had IBS according to the Rome I criteria, a prevalence of 4% (95% CI: 3.6%
      4.4%). IBS was more frequent in women (5.3%) than in men (2.5%), with a sex ratio
      (F/M) of 2.3. In 9.1% of sufferers, onset had occurred less than 12 months ago, a
      yearly incidence of 3.6 per 1,000 of the population. In 32.3% of IBS sufferers
      diarrhoea was predominant, and in 34.6% constipation was predominant. Of IBS
      sufferers 83.7% had consulted a physician for their condition, and 87.6% had
      taken medication for their IBS symptoms over the previous 12 months. CONCLUSION:
      The prevalence of IBS observed in this study in France was close to the lower
      limit in published data (3 to 20%). Our results suggest that the Rome I criteria
      are not sensitive enough to detect all IBS patients in a population not actively
      seeking health care intervention for the condition. In this regard, the refined
      classification (Rome II) which was established after our study was carried-out
      should be evaluated.

PMID- 12520201
TI  - [Patient-doctor relationship in the irritable bowel syndrome. Results of a French
      prospective study on the influence of the functional origin of the complaints].
AB  - The attention given by the physician and the quality of the patient-physician
      relationship mainly determine the outcome of a consultation. Care seeking is a
      main characteristic of patients with functional bowel disorders, including
      irritable bowel syndrome (IBS), while patients with suspected organic disease
      (Org) would rather expect a precise answer about their condition. The aim of this
      study was thus to evaluate the outcome of the consultation with a
      gastroenterologist in IBS patients, as compared to a group of patients with
      suspected organic disease. PATIENTS AND METHODS: A prospective multicenter cross
      sectional study "one given week" included 158 patients consulting for the first
      time 18 gastroenterologists. Patients were consulting for abdominal pain and were
      classified as IBS or Org on the basis of the physician's clinical impression.
      Questionnaires including 27 common questions were distributed to the patients and
      the physicians at the end of the consultation and filled separately. RESULTS: The
      diagnosis of IBS was done in 110 patients and that of Org in 48. Groups were
      comparable for the characteristics, the intensity and the frequency of attacks of
      abdominal pain. The index of satisfaction of the patients was not different
      between groups (IBS: 8.7 +/- 1.4; Org: 9.1 +/- 1.4; P=0.16). The intensity of
      abdominal pain was reported in the same range by the patient (IBS: 5.1 +/- 2.9;
      Org: 4.5 +/- 2.8) and the physician (IBS: 4.6 +/- 2.3; Org: 4.8 +/- 2.6) in both
      groups. Digestive and extra-digestive symptoms were quoted equally by physicians,
      whatever the group the patient belonged to. Information given by the physician on
      diagnosis and therapy were equally well perceived by patients of both groups.
      However, the physician tended to evaluate the efficacy of the prescribed therapy
      to be lower in IBS (7.1 +/- 2.0) than in Org patients (8.0 +/- 1.7; P<0.01).
      CONCLUSION: In this study, the consultation with a gastroenterologist is equally
      well perceived by IBS and Org patients and it seems to meet the expectancy of the
      patient in most cases. However, the physician appeared less confident in the
      efficacy of the therapy proposed to IBS patients.

PMID- 12520202
TI  - [Somato-psychiatric interactions in celiac disease].

PMID- 12520203
TI  - [What can be done for patients with cancer of the digestive tract in 2003?
      Guidelines of the Francophone Federation of Digestive Tract Cancerology - Part
      I].

PMID- 12520204
TI  - [Regression of hepatocellular carcinoma under Tamoxifen: report of one case and
      review of the literature].
AB  - Hepatocellular carcinoma is a malignant tumor with a poor prognosis, particularly
      when it is unresectable. The results of tamoxifen treatment in hepatocellular
      carcinoma have been disappointing and randomized studies have shown conflicting
      results. We report the case of a 72-yr-old-man with histologically confirmed
      hepatocellular carcinoma on a normal liver, that regressed with tamoxifen
      treatment. Regression was confirmed by normalization of serum alpha-fetoprotein
      levels and a significant decrease in radiological lesions by 66%. The patient was
      alive in excellent clinical condition more than 30 months after the initial
      diagnosis.

PMID- 12520205
TI  - [Squamous cell carcinoma of the celiac area. Report of a case and review of the
      literature].
AB  - Primary squamous cell carcinoma of the pancreas or of the stomach is rare and
      represents a controversial entity. The unusual case of a 50-year-old woman with a
      large squamous cell carcinoma located in the celiac area and involving liver,
      stomach and pancreas, is reported here. The patient underwent complete surgical
      resection. The microscopic diagnosis was well-differentiated squamous cell
      carcinoma without glandular structure. Following the procedure, search for
      another possible primary lesion (esophagus, anus, colon, lung, head and neck,
      pelvic floor) was performed. This search was negative. In this context, final
      diagnosis was primary gastric or pancreatic squamous cell carcinoma. Local
      recurrence located in the eso-jejunal anastomosis was discovered three years
      later. Subsequent radiation combined with chemotherapy was instituted, allowing
      complete remission. During the subsequent 27-month follow-up, no local or
      systemic recurrence was observed. Pathogenesis of gastric as well as pancreatic
      primary squamous cell carcinoma remains obscure and controversial. These tumors
      usually have a very poor prognosis with rapid vascular and lymphatic involvement.
      Nevertheless, favorable outcome seems possible, as exhibited in our patient.

PMID- 12520206
TI  - [Intraductal papillary mucinous tumor with pancreatobiliary and
      pancreatodigestive fistulae: a case report].
AB  - Pancreatobiliary or pancreatodigestive fistulae are rare during the course of
      intraductal papillary mucinous tumors. The mechanism of the fistula is either
      malignant involvement or mechanical. We report the case of an 81-year-old patient
      with intraductal papillary mucinous tumor complicated by fistulae between the
      main pancreatic duct and common bile duct, duodenum and stomach. These fistulae
      were treated endoscopically and radiologically by several metallic stents.

PMID- 12520207
TI  - [Lyme's disease presenting as increased gamma-GT activity].

PMID- 12520208
TI  - [Microvacuolar steatosis following low doses of doxycycline].

PMID- 12520209
TI  - [Chronic dysphagia by impaction of drug packaging after general anesthesia].

PMID- 12520210
TI  - [Acinous-cell carcinoma of a metastatic pancreas treated by chemotherapy].

PMID- 12520211
TI  - [Implication of nitrogen oxide producing enzymes in the pathophysiology of
      fulminant hepatitis].

PMID- 12520219
TI  - [Evaluation of t(1)-weighted black blood imaging using triple inversion
      recovery].
AB  - The black blood sequence, in which the blood signal is suppressed, fundamentally
      provides T(2)-weighted images. We developed a T(1)-weighted black blood sequence.
      This new sequence improved the triple IR sequence that uses three inversion
      pulses by continuously providing three inversion pulses. By so doing, the
      sequence lengthens the time from the third inversion pulse to data sampling. The
      new sequence sets the flip angle of the third inversion pulse to 95-110 degrees.
      Consequently, the difference in T(1) is emphasized in favor of the longitudinal
      magnetization component with the null point of blood. Data sampling uses the fast
      spin-echo sequence of a wide sampling bandwidth. The wide bandwidth shortens echo
      space. T(1)-weighted black blood images were obtained by these methods. Fat
      suppression is possible by using a CHESS pulse before data sampling.

PMID- 12520220
TI  - Allergies correlated to adverse reactions induced by non-ionic monomeric and
      ionic dimeric contrast media for contrast enhanced CT examination.
AB  - Although contrast media are indispensable for x-ray diagnosis, they are
      xenobiotics and may cause undesirable adverse reactions. We have correlated
      several allergies to the adverse reactions caused by three representative
      contrast media in order to predict and prevent possible problems. The adverse
      reactions were observed at probabilities of up to 100%(odds ratio 8.0) in drug
      allergy and contact dermatitis patients. These allergies were proven in this
      study to be type IV reactions, and all the observed adverse reactions were
      classified as allergies of either type I or IV. Thus, one can predict to some
      extent even the time when the adverse reaction will appear after the injection of
      contrast medium. Finally, a questionnaire to be administered prior to contrast
      enhanced CT examinations has been proposed. The questionnaire is designed to
      predict adverse reactions on the basis of statistical analysis. Since the
      physicochemical properties of contrast media are different, this questionnaire is
      also useful for selecting the most suitable contrast medium for the patient.

PMID- 12520221
TI  - [Survey of bone mineral density in residents of selected areas of Hiroshima
      prefecture: effects of age and constitution on bone mineral density].
AB  - Because the complications of decreased bone mineral density, such as femoral neck
      fractures and severe spinal deformities, have a strong impact on daily life,
      prevention has become more important than therapy. The present study included as
      subjects 771 women residing in Innoshima City, Sera-gun, and Mihara City, all in
      Hiroshima Prefecture. We determined bone mineral density in the lumbar spine and
      femoral neck of these women, measured their height and weight, and examined the
      effect of age and body mass index (BMI) on bone density rate (YAM%). The subjects
      of the study were all volunteers. As no significant difference could be
      demonstrated in comparison with the results of the 1998 National Nutrition Survey
      of height, body weight, and BMI, we considered there would be no problem in
      extrapolating the results of the present determinations to middle-aged and
      elderly women. In the relationship between age and YAM%, a negative trend was
      observed prior to menopause, but was not significant. After menopause, however, a
      significant negative correlation was demonstrated. In addition, a significant
      positive correlation was observed between BMI and age-corrected YAM% for the
      lumbar spine and femoral neck. In future studies, the YAM% of the lumbar spine
      and femoral neck corrected for age and BMI should be investigated to determine
      the influence of lifestyle.

PMID- 12520222
TI  - [New method of measuring presampling MTF by fourier transform of square-wave
      chart image].
AB  - We developed an easy method of measuring the presampling modulation transfer
      function (MTF) using the square wave chart in digital radiography. In this
      method, the presampling MTF is measured by Fourier transform of image data of the
      square wave chart. When Fourier analysis of the sampling data of a square wave is
      carried out, it is generally difficult to find the starting point and terminal
      point of the periodic data that should be extracted because of an insufficient
      number of data. To solve this problem, interpolated data were calculated by using
      a window function of the frequency domain. The aliasing error was avoided using a
      characteristic such that the square wave has discrete frequency components. The
      accuracy of this method was investigated by computer simulation study. Actual
      measurement of the presampling MTF by this method was also performed with a CR
      system. These studies indicated the effectiveness of our proposed method in terms
      of accuracy and ease of use.

PMID- 12520224
TI  - [Financial impact of introducing filmless CRT diagnosis].
AB  - There has been a great deal of discussion as to the cost and benefit of
      introducing filmless CRT diagnosis for radiological exams. Although the various
      advantages of the filmless system tend to be highlighted, very few studies have
      attempted to provide a quantitative estimate of the degree of impact. We analyzed
      the potential financial impact on the cost of film management (film development,
      maintenance, and transportation) if CRT diagnosis were to be introduced in Seirei
      Hamamatsu Hospital. In conducting this analysis, we assumed that CRT diagnosis
      initially would be limited to CT and MR. The analysis demonstrated that the
      actual yearly cost of managing films amounts to about 240 million yen. As
      individual items, the cost of film materials, labor, and depreciation of assets
      were the three largest cost sectors, with the cost of film accounting for more
      than 30% of the total. The expense attributable to CT and MR exams was roughly
      half of the total cost. Against this level of expense, the expected savings in
      the first year after shifting to the filmless system would be 100 million yen, or
      a 36% reduction in current expenses. This savings reflects various effects of
      system change, including lack of need for related materials, reduction in staff
      workload, elimination of unnecessary equipment, etc. Under the simulation we
      conducted, 70% of savings occurred in the area of variable costs and 30% in the
      area of fixed costs.

PMID- 12520223
TI  - [Development of an image processing scheme for chest radiographs using a dot
      printer].
AB  - The performance of dot printers has recently been improved. Images output by dot
      printers can provide simple, economical medical reference images if important
      diagnostic information is not lost. We developed an image processing scheme for
      chest radiographs that employed a dot printer. We used two types of pixel value
      conversions, a nonlinear pixel value correction using a lookup table and a linear
      pixel value conversion using histogram analysis. The density distribution of
      chest radiographs was analyzed and classified into high-density and low-density
      images. The two types of pixel value conversions were used depending on the
      density of chest radiographs. Converted pixel value had density characteristics
      that were adapted to the output image of the dot printer, and thus the density
      distributions of the lungs of radiographs became comparable. In addition, an
      adaptive unsharp masking technique with processing parameters optimized for each
      of the lungs and mediastinum was applied. An ROC study for the detection of lung
      nodules was carried out to evaluate the performance of dot printer images. The
      area under the ROC curve (A(z)) for dot printer images was 0.816, while
      sensitivity and specificity were 77.6% and 75.2%, respectively. The performance
      indicated the usefulness of our image processing scheme.

PMID- 12520226
TI  - [In situ therapy of deep-seated canver by radioactive microspheres].

PMID- 12520225
TI  - [Clinical application of a spot filter for exposure dose reduction].
AB  - An added filter on the collimator of the X-ray tube is useful for reducing
      exposure dose in interventional radiology (IVR). During IVR, high-quality
      fluoroscopic images are needed around the target region, but the portion of the
      fluoroscopic image that shows catheter/guide wires need not to be of high
      quality. Thus, we constructed an additional filter (spot filter) consisting of a
      copper sheet with an open hole in the center. The spot filter is moved by a
      remote control technique and can be used in cases of neurological, cardiac,
      abdominal, and pelvic IVR. Using this filter, image quality was improved at the
      target region of the image intensifier, because scatter radiation was attenuated
      in the periphery. Although image quality was deteriorated in the periphery, there
      was no significant disadvantage for IVR. The spot filter would be effective in
      reducing exposure dose in cases where the image quality of the target region
      needs to be maintained and in prolonged fluoroscopy.

PMID- 12520227
TI  - [Digital imaging technology from the viewpoint of optics].

PMID- 12520228
TI  - [Basics of three dimensional image processing].

PMID- 12520229
TI  - [3D- CT angiography (3D-CTA) of the head and neck regions].

PMID- 12520230
TI  - [Quality assurance for radiation oncology in Germany-Uniklinikum der Freiburg-].

PMID- 12520231
TI  - [Evaluation and routine testing in medical imaging departments part 2-5: Contancy
      tests-imaging display devices].

PMID- 12520232
TI  - [The report of the electromagnetic interference at the medical facilities
      (questionnaire for the enterprise)].

PMID- 12520233
TI  - [A practice of various quantitative methods for cerebral blood flow using brain
      SPECT--notes in clinical application].

PMID- 12520234
TI  - [Apparatus engineering of X ray CT equipment (4) : Development of multi slice
      CT].

PMID- 12520235
TI  - [The radiation safety guideline for installation adjustment of the high energy
      medical radiation generators (medical linear acceleratar)].

PMID- 12520236
TI  - [New method of screening chest radiography with computer analysis of respiratory
      kinetics].
AB  - To develop a new method of screening chest radiography that would provide
      respiratory kinetics easily and automatically using flat-panel-detector
      capacitated fluoroscopy, we carried out a motion analysis of the diaphragm at
      several respiratory phases. We obtained five chest radiographs of healthy
      volunteer at five respiratory phases, from maximum inspiration to normal
      expiration. The edges of the diaphragm were enhanced by the first derivative
      filter, which select edge graduents within a limited range of orientations, and
      were detected by thresholding and analysis of connectivity in the horizontal
      direction. We measured the distance from the apex to the diaphragm as well as the
      changes at each phase. The apex was determined previously at the step of lung
      region recognition. At the costophrenic angle, the change in the distance from
      the apex to the diaphragm was 2.44 cm on the right and 3.06 cm on the left, while
      at the paramedian region the changes were 0.74 cm on the right and 1.36 cm on the
      left. This new method of chest examination with computer analysis can provide
      information on diaphragm kinetics during respiration. In addition, it may aid in
      the early diagnosis of diseases such as chronic pulmonary emphysema and phrenic
      nerve paralysis.

PMID- 12520237
TI  - [Evaluation of median filtering after reconstruction with maximum likelihood
      expectation maximization (ML-EM) by real space and frequency space].
AB  - Maximum likelihood expectation maximization (ML-EM) image quality is sensitive to
      the number of iterations, because a large number of iterations leads to images
      with checkerboard noise. The use of median filtering in the reconstruction
      process allows both noise reduction and edge preservation. We examined the value
      of median filtering after reconstruction with ML-EM by comparing filtered back
      projection (FBP) with a ramp filter or ML-EM without filtering. SPECT images were
      obtained with a dual-head gamma camera. The acquisition time was changed from 10
      to 200 (seconds/frame) to examine the effect of the count statistics on the
      quality of the reconstructed images. First, images were reconstructed with ML-EM
      by changing the number of iterations from 1 to 150 in each study. Additionally,
      median filtering was applied following reconstruction with ML-EM. The quality of
      the reconstructed images was evaluated in terms of normalized mean square error
      (NMSE) values and two-dimensional power spectrum analysis. Median filtering after
      reconstruction by the ML-EM method provided stable NMSE values even when the
      number of iterations was increased. The signal element of the image was close to
      the reference image for any repetition number of iterations. Median filtering
      after reconstruction with ML-EM was useful in reducing noise, with a similar
      resolution achieved by reconstruction with FBP and a ramp filter. Especially in
      images with poor count statistics, median filtering after reconstruction with ML
      EM is effective as a simple, widely available method.

PMID- 12520238
TI  - [CT scanners with automatic focus alteration capability].
AB  - Heat accumulation in X-ray tubes results in disarrangement of focus owing to heat
      expansion of the anode. CT scanners with automatic focus alteration capability
      have been developed to counteract this problem. We compared CT scanners with and
      without focus alteration capabilities and discuss the effect of focus
      disarrangement on the CT images. Images were obtained when heat accumulation was
      high and low. Subtraction images were made to define the disarrangement of focus.
      A comparison was made between CT scanners with and without automatic focus
      alteration capability. ROI was selected and changes in CT values, SD, and slice
      thickness were observed under changing anode heat accumulation. Results indicated
      that images from both scanners showed disarrangement of the focus and elevation
      of CT values as anode heat accumulated. However, the scanner with automatic focus
      alteration produced images with less focus disarrangement from the center of the
      slice and less elevation of CT values. Scanners with automatic focus alteration
      are less prone to the focus disarrangement and elevation of CT values caused by
      anode heat accumulation and enable reproducible images to be obtained.

PMID- 12520239
TI  - [Influence of deficit in top-of-the-head CT images on STI dose calculation].
AB  - In 54 cases of stereotactic irradiation (STI) seen at our hospital from April
      2000 to March 2001, we examined the deficit in top-of-the-head computed
      tomography (CT) images and the influence that this deficit had on calculation of
      the STI dose. Results showed a slice deficit of more than 5 mm in 16 of the 54
      cases and a maximum deficit of 25 mm. In most cases, the Gill-Thomas-Cosman (GTC)
      frame was used. The error in total dose monitor unit (DMU) calculation can be
      ignored if the top-of-the-head CT image deficit is less than 10 mm. If the
      deficit is more than 20 mm, it is possible that the total DMU calculation error
      will exceed 2  . In cases in which the deficit was greater than 30 mm, the
      average calculation error was 2.00  , and, in one case, the error was more than 7
      . The GTC frame tends to produce CT image deficits in top-of-the-head images,
      whereas such images do not suffer this loss when a Brown-Roberts-Wells (BRW) head
      ring is used. When the CT image deficit is large, it is necessary to reduce the
      ratio of the arc that passes the area of the CT image deficit and to decrease the
      dose weight of the arc.

PMID- 12520240
TI  - [Effect of sharpening filter on vessel diameter measured by quantitative coronary
      arteriography].
AB  - At cardiac catheterization, analog images obtained using cinefilm are translated
      into digital images, and images appearing on the CRT are filtered by a sharpen
      filter. We investigated the effect of the sharpening filter on vessel diameter as
      measured by quantitative coronary arteriography. We acquired images of a vessel
      phantom filled with contrast material using an X-ray image intensifier. Vessel
      diameters measured by quantitative coronary arteriography were 1 mm, 1.5 mm, 2
      mm, 3 mm, 4 mm, and 6 mm. Results showed that vessel diameters were decreased
      when the sharpening filter was used and that more intense filtering decreased the
      measured diameter further. When the diameter of the vessel phantom was less than
      4 mm, the diameter was smaller and the ratio of decrease was larger. Vessel
      diameters of 2 mm, 3 mm, 4 mm, and 6 mm measured a maximum of 2.9   smaller,
      while those of 1 mm and 1.5 mm measured a maximum of 9.2   smaller.

PMID- 12520241
TI  - [Visualization by dynamic CT: invention of 2D-CT chronogram].
AB  - Dynamic computed tomography is one of the methods used for the functional
      analysis of blood flow information. We devised a simple method of visualization
      for dynamic CT. Re-sliced images were stacked as multi-slice images for the
      different acquisition times to show a continuous spatial arrangement with dynamic
      data. Images processed into re-sliced images termed 2D-CT Chronograms were
      observed in many directions and were useful for comprehending the blood flow
      function of the target organ. Time-density curves with motion dependency and
      color displays similar to those of ultrasound images are easily acquired from the
      2D-Chronogram. We introduce some clinical applications of the 2-D Chronogram.

PMID- 12520242
TI  - [Simulation study of scan timing in three-dimensional contrast-enhanced MR
      angiography].
AB  - In our study of three-dimensional contrast-enhanced MR angiography, we performed
      a computer simulation to quantitatively investigate vessel visibility according
      to scan timing. To construct the simulated MR images, we varied the position
      (scan timing) and range (enhancement-duration) of k-space data assumed to be
      acquired during contrast enhancement. In the present study, either the sequential
      or centric phase-encoding order in k(y) and k(z) on k-space was assumed to be
      used. When scan timing was shifted from the optimal timing, the visibility of
      thick vessels decreased, and the signal intensity in thin vessels was higher than
      that in thick vessels. We found that the appropriate setting of scan timing was
      an important factor in the visibility of thick vessels. Meanwhile, we also noted
      that extending the enhancement-duration (or shortening the scan time) could
      increase the visibility of thin vessels. Our results and the simple technique
      used for simulation are considered to be useful for the study of three
      dimensional contrast-enhanced MR angiography.

PMID- 12520243
TI  - Critical choices in mentoring the next generation of academic pediatricians: nine
      circles of hell or salvation?

PMID- 12520244
TI  - Getting the lead out: can iron help?

PMID- 12520245
TI  - Gender, death and cystic fibrosis: is energy expenditure a component?

PMID- 12520246
TI  - Neurologic and developmental morbidity in children with complex congenital heart
      disease.

PMID- 12520247
TI  - Association between iron deficiency and blood lead level in a longitudinal
      analysis of children followed in an urban primary care clinic.
AB  - OBJECTIVE: To determine if iron deficiency (ID) is longitudinally associated with
      lead poisoning. STUDY DESIGN: Blood lead levels, hemoglobin, mean corpuscular
      volume (MCV), red cell distribution width (RDW), insurance status, and age were
      determined for 1,275 children. ID was defined as MCV <70 fl and RDW >14.5 if age
      was <2 years and MCV <73 fl and RDW >14.5 if age was >/=2 years. Logistic
      regression models were constructed by using the second-visit blood lead levels
      dichotomized at >/=0.48 microm/L (10 microg/dL) as the outcome. RESULTS: The odds
      ratio (OR) for baseline ID predicting lead poisoning at the second visit was 4.12
      (95% CI, 1.96-8.65). In the second model, using children who were iron-replete at
      both visits as the referent group, for children with ID at both visits, the OR
      for predicting lead poisoning at the second visit was 5.54 (95% CI, 2.25-13.62).
      For children with ID at the first visit and iron-replete at the second visit, the
      OR was 2.73 (95% CI, 0.90-8.27), and for children iron-replete at the first visit
      and ID at the second visit, the OR was 0.81 (95% CI, 0.10-6.30). CONCLUSIONS: ID
      is associated with subsequent lead poisoning. These data are consistent with a
      biological mechanism of increased lead absorption among iron deficient children.

PMID- 12520248
TI  - Differences in resting energy expenditure between male and female children with
      cystic fibrosis.
AB  - OBJECTIVES: To evaluate which factors might contribute to raised resting energy
      expenditure (REE) in patients with cystic fibrosis (CF). STUDY DESIGN: REE and
      anthropometry were measured in 134 (males = 68) children with CF and 100 (males =
      51) controls (range, 3-18.7 years) in an outpatient setting. Bacterial
      colonization, liver disease, inhaled steroid use, pancreatic and pulmonary
      function, sex, and genotype were determined and regression analysis was used to
      determine the predictors of REE in the group with CF. RESULTS: REE for children
      with CF was increased on average by 7.2% compared with controls. This increase
      was greater for females than for males. REE in males was positively associated
      with fat-free mass (FFM), pancreatic insufficiency (PI), and liver disease, and
      negatively associated with pulmonary function, whereas in females, REE was
      positively associated with FFM and PI. REE (adjusted for FFM) was higher in
      children with a severe mutation (5495 +/- 47 kJ) compared with a mild mutation
      (5,176 +/- 124 kJ, P <.02). CONCLUSIONS: PI, severe mutations, and female sex are
      the main contributing factors to elevated REE in patients with CF with near
      normal pulmonary function.

PMID- 12520249
TI  - Developmental outcome of patients with hypoplastic left heart syndrome treated
      with heart transplantation.
AB  - OBJECTIVE: To describe the outcome of children treated for hypoplastic left heart
      syndrome (HLHS) with heart transplantation. STUDY DESIGN: We evaluated outcomes
      in 26 children treated for HLHS in a single center; 13 children were evaluated
      with the Bayley Scales of Infant Development, Child Behavior Checklist (CBCL),
      and Vineland Adaptive Behavior Scales (VABS), and 13 were seen after 36 months of
      age and were evaluated with the Wechsler Preschool and Primary Scale of
      Intelligence, CBCL, and VABS at 36 to 72 months or the Wechsler Intelligence
      Scale for Children-III, CBCL, and VABS for those older than 72 months of age.
      RESULTS: Bayley Scales of Infant Development results revealed a median Mental
      Developmental Index of 88 (range <50 to 102) and a Psychomotor Developmental
      Index of 86.5 (<50 to 113), both significantly lower than expected in the general
      population. Intelligence quotient results on either the Wechsler Preschool and
      Primary Scale of Intelligence or Wechsler Intelligence Scale for Children-III
      were also significantly lower than expected, with a mean verbal score of 90.5 +/-
      12.4, performance score of 88.9 +/- 14.5, and full scale score of 88.5 +/- 13.0.
      On the Vineland scales, 39% scored >1 SD below the mean on measures of daily
      living scales, 22% on the socialization subscale, 48% on the communication
      subscale, and 52% on the adaptive behavior scale. CONCLUSIONS: In this small
      population of children treated for HLHS with heart transplantation, both
      cognitive deficits and adaptive/behavioral abnormalities are described. Early
      identification with appropriate referral for services could potentially enhance
      the outcomes for these children.

PMID- 12520250
TI  - Effect of cardiopulmonary bypass on urea cycle intermediates and nitric oxide
      levels after congenital heart surgery.
AB  - OBJECTIVE: To test the hypothesis that cardiopulmonary bypass used for repair of
      ventricular septal defects and atrioventricular septal defects would decrease
      availability of urea cycle intermediates including arginine and subsequent nitric
      oxide availability. STUDY DESIGN: Consecutive infants (n = 26) undergoing
      cardiopulmonary bypass for repair of an unrestrictive ventricular septal defect
      or atrioventricular septal defect were studied. Blood samples were collected
      immediately before surgery, immediately after surgery, and 12 hours, 24 hours,
      and 48 hours after surgery. Urea cycle intermediates, including citrulline,
      arginine, and ornithine, were measured by amino acid analysis. Nitric oxide
      metabolites were measured by means of the modified Griess reaction. RESULTS:
      Cardiopulmonary bypass caused a significant decrease in the urea cycle
      intermediates arginine, citrulline, and ornithine at all postoperative time
      points compared with preoperative levels. The ratio of ornithine to citrulline, a
      marker of urea cycle function, was elevated at all postoperative time points
      compared with preoperative values, indicating decreased urea cycle function.
      Nitric oxide metabolites were significantly decreased at all postoperative time
      points except for 48 hours, compared with preoperative levels. CONCLUSIONS:
      Cardiopulmonary bypass significantly decreases availability of arginine,
      citrulline, and nitric oxide metabolites in the postoperative period. Decreased
      availability of nitric oxide precursors may contribute to the increased risk of
      postoperative pulmonary hypertension.

PMID- 12520251
TI  - Maternal cell microchimerism in newborn tissues.
AB  - OBJECTIVES: On the basis of reports of maternal cells being detected in the
      umbilical cord blood of newborn infants, we tested the hypothesis that maternal
      cells can migrate out of the circulation into newborn tissues. STUDY DESIGN: We
      studied autopsy material from 4 newborn infants who never received a blood
      transfusion and died during the first week of life. The study subjects' diagnoses
      were trisomy 21 with nonimmune hydrops, 46, XY, 4q+ with multiple congenital
      anomalies, Potter syndrome, and congenital ichthyosis. Fluorescence in situ
      hybridization analysis with X and Y chromosome-specific probes was performed on
      sections of paraffin-embedded tissue, including liver, spleen, thymus, thyroid,
      and skin. RESULTS: Female cells, as defined by the presence of intact nuclei with
      two X chromosome signals, were detected in multiple tissue types from all 4 male
      neonates. The number of female cells varied from 3 to 45 per slide. CONCLUSIONS:
      Maternal cells enter the fetal circulation and are capable of migration to fetal
      and neonatal organs. This is of importance with regard to potential consequences
      of umbilical cord blood transplantation and postnatal development of autoimmune
      disease.

PMID- 12520252
TI  - The maturation and coordination of sucking, swallowing, and respiration in
      preterm infants.
AB  - OBJECTIVES: Our objectives were to establish normative maturational data for
      feeding behavior of preterm infants from 32 to 36 weeks of postconception and to
      evaluate how the relation between swallowing and respiration changes with
      maturation. STUDY DESIGN: Twenty-four infants (28 to 31 weeks of gestation at
      birth) without complications or defects were studied weekly between 32 and 36
      weeks after conception. During bottle feeding with milk flowing only when infants
      were sucking, sucking efficiency, pressure, frequency, and duration were measured
      and the respiratory phase in which swallowing occurs was also analyzed.
      Statistical analysis was performed by repeated-measures analysis of variance with
      post hoc analysis. RESULTS: The sucking efficiency significantly increased
      between 34 and 36 weeks after conception and exceeded 7 mL/min at 35 weeks. There
      were significant increases in sucking pressure and frequency as well as in
      duration between 33 and 36 weeks. Although swallowing occurred mostly during
      pauses in respiration at 32 and 33 weeks, after 35 weeks swallowing usually
      occurred at the end of inspiration. CONCLUSIONS: Feeding behavior in premature
      infants matured significantly between 33 and 36 weeks after conception, and
      swallowing infrequently interrupted respiration during feeding after 35 weeks
      after conception.

PMID- 12520253
TI  - Newborn hearing screening: tobramycin and vancomycin are not risk factors for
      hearing loss.
AB  - OBJECTIVE: To investigate the chance of detecting hearing loss with neonatal
      hearing screening in relation to exposure to tobramycin and vancomycin. STUDY
      DESIGN: Automated auditory brainstem response (A-ABR) hearing screening was
      performed in all neonates with at least one risk factor. Data on drug
      administration were abstracted from patient files. Exposure to these drugs was
      related to the result of hearing screening. In patients failing hearing
      screening, exposure to ototoxic medication was assessed in the light of other
      risk factors for hearing loss. RESULTS: Six hundred twenty-five patients were
      analyzed; 45 neonates failed hearing screening. Tobramycin, vancomycin, and
      furosemide were used in 508, 130, and 174 patients, respectively. Exposure to
      vancomycin, tobramycin, or furosemide or a combination, defined in terms of
      treatment duration, total dose, or serum concentrations of antibiotics, was not
      related to failure to pass A-ABR screening. Ototoxic medication was not the most
      probable risk factor in any of the patients with serum concentrations outside the
      therapeutic range. CONCLUSIONS: Routine therapeutic drug monitoring of vancomycin
      and tobramycin in neonates for ototoxicity reasons is not helpful in detecting
      patients at risk for clinically important hearing loss in the 2- to 4-kHz range.
      A longer period of audiometric follow-up is needed to determine any long-term
      effects.

PMID- 12520254
TI  - Pharmacokinetics and tolerance of zidovudine in preterm infants.
AB  - OBJECTIVE: To determine zidovudine pharmacokinetics and tolerance in premature
      human human immunodeficiency virus-exposed infants. STUDY DESIGN: Pediatric AIDS
      Clinical Trials Group Study 331 was a multicentered prospective, open-label study
      of the use of zidovudine in premature infants. Thirty-eight infants <35 weeks'
      gestational age (GA) were studied while receiving zidovudine 1.5 mg/kg every 12
      hours until 2 weeks of age, then 2.0 mg/kg every 8 hours until 6 weeks of age.
      Population pharmacokinetics were evaluated at 1, 2, and 4 weeks' postnatal age;
      zidovudine doses were adjusted to maintain troughs <3 microM. RESULTS: Zidovudine
      clearance was lower than reported in term infants at similar postnatal ages. Nine
      premature infants required dose reduction because of high levels (7/19 <30 weeks'
      and 2/19 >/=30 weeks' GA). Postnatal age, GA, serum creatinine, and furosemide
      use independently predicted zidovudine clearance. Zidovudine was generally well
      tolerated in this high-risk population. CONCLUSIONS: Zidovudine clearance is
      greatly reduced in premature infants. We recommend the following zidovudine
      dosing schedule in this population: 1.5 mg/kg (intravenous) or 2.0 mg/kg (oral)
      every 12 hours increased to every 8 hours at 2 weeks of age (>/=30 weeks' GA) or
      at 4 weeks (<30 weeks' GA).

PMID- 12520255
TI  - Montelukast pharmacokinetics in cystic fibrosis.
AB  - OBJECTIVES: To determine if patients with cystic fibrosis (CF) have an altered
      pharmacokinetic profile of montelukast, we studied the single-dose
      pharmacokinetics in 12 patients with CF and 12 age- and gender-matched controls
      after they received a 10-mg oral dose. METHODS: Plasma samples were collected
      before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours
      after drug administration. The specimens were analyzed by high-performance liquid
      chromatography (HPLC). RESULTS: The mean systemic clearance (mL/min) values (+/-
      SD) were not statistically different between the CF subjects (55.53 +/- 44.0
      mL/min) and the controls (57.12 +/- 18.42 mL/min), nor were the results
      significantly different when normalized to body surface area or body weight. The
      mean value for elimination half-life, elimination rate constant, area under the
      plasma concentration versus time curve, and maximum concentration for controls
      was 2.37 +/- 0.38 hours, 0.30 +/- 0.05 hours(-1), 2,680.0 +/- 693.6 ng. min/mL,
      and 448.9 +/- 165.3 ng/mL; and for the CF patients it was 2.97 +/- 1.21 hours,
      0.28 +/- 0.13 hrs(-1), 3976.1 +/- 2073.4 ng. min/mL, 606.7 +/- 237.8 ng/mL. There
      were no statistically significant differences (all P >.05) in the measured
      pharmacokinetic parameters between the CF and control subjects. CONCLUSIONS: We
      conclude that the dose of montelukast and the dosing interval does not need to be
      modified if the goal is to mimic the serum concentration used to treat asthma.
      The effectiveness of these concentrations for the inflammatory lung disease of
      patients with CF is unknown.

PMID- 12520256
TI  - Efficacy of telephone teaching of conservative therapy for infants with
      symptomatic gastroesophageal reflux referred by pediatricians to pediatric
      gastroenterologists.
AB  - OBJECTIVES: To evaluate the efficacy of a specific protocol of conservative
      therapy for infant gastroesophageal reflux. STUDY DESIGN: Retrospective
      evaluation of the response to telephone teaching of conservative therapy by a
      single instructor as part of the screening process for a pharmacotherapy study of
      infantile reflux. Feeding modifications included the use of a protein-hydrolysate
      formula thickened with one tablespoon of dry rice cereal per ounce, at restricted
      volumes. Positioning changes included avoidance of seated and supine positions.
      Elimination of all tobacco smoke exposure was advised. SETTING: Single-center,
      outpatient. SUBJECTS: 394 infants <12 months old. ANALYSIS:  EFFICACY: the
      percentage responding to conservative therapy instruction. Factors possibly
      predicting success for isolated conservative therapy instruction: evaluated as
      explanatory variables by chi(2) analysis; significance at P <.05. RESULTS: Ninety
      six infants (24%) had sufficient symptom improvement and no additional
      intervention was required. Infants with isolated vomiting or irritability were
      more likely to respond than infants with both or other symptoms (P <.001).
      Neither formula type fed nor use of pharmacotherapy at referral were significant
      in determining response to conservative therapy. CONCLUSIONS: As many as 24% of
      infants with gastroesophageal reflux disease may respond to conservative therapy
      instruction provided by telephone. Benefits include savings of cost, time, and
      drug exposure of infants.

PMID- 12520257
TI  - The effect of short-term dimethylglycine treatment on oxygen consumption in
      cytochrome oxidase deficiency: a double-blind randomized crossover clinical
      trial.
AB  - OBJECTIVE: To study the effectiveness of dimethylglycine (DMG) on oxygen
      consumption (VO(2)) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase
      (SLSJ-COX) deficiency (OMIM 220111). STUDY DESIGN: In a crossover randomized
      double-blind clinical trial, 5 children with SLSJ-COX deficiency, who were stable
      and old enough to comply with VO(2) measurement, were treated with placebo or DMG
      for 3 days, and with the alternate treatment after a 2-week washout period. VO(2)
      was measured by indirect calorimetry before and after treatment. Dietary caloric
      intake was calculated for 3 days before each measurement. Mean caloric intakes
      per day were 1562 and 1342 kcal x m(-2) before and during placebo, 1,336 and
      1,380 before and during DMG, respectively. RESULTS: DMG was well tolerated and,
      in all cases, resulted in markedly increased blood DMG levels (617 + 203 mmol x
      L(-1)), versus 0 to 2 mmol x L(-1) without treatment. Mean VO(2) was lower after
      administration of either DMG (-1 +/- 3 mL x min(-1) x m(-2)) or placebo (-6 +/-
      4), but neither difference was statistically significant. There was no detectable
      effect of DMG treatment on blood levels of lactate, pyruvate, bicarbonate, or pH.
      VO(2) values of patients (range, 101-135 mL x min(-1) x m(-2)) were lower than
      published norms (150-160 mL x min(-1) x m(-2)). CONCLUSION: This study suggests
      that treatment with DMG does not substantially change VO(2) in children with SLSJ
      COX deficiency.

PMID- 12520259
TI  - Improving body composition and physical activity in Prader-Willi Syndrome.
AB  - OBJECTIVE: To determine if muscle training in Prader-Willi Syndrome (PWS) can
      improve local body composition, physical capacity, and activity. STUDY DESIGN:
      Seventeen children and adolescents with PWS and 18 control children were enrolled
      in a daily short calf muscle training program for 3 months. Before (t(0)) and
      after 3 months of training (t(3m)), spontaneous physical activity and exercise
      capacity were assessed by pedometer registrations and activity protocols. Local
      body composition was determined by calf circumference and skinfold measurements
      at t(0), t(3m), and 3 months after t(3m) (t(6m)). RESULTS: During training, calf
      skinfold decreased from 1.1 to 0.8 SD (P <.01) and calf circumference in PWS
      increased from 1.4 to 1.9 SD (P <.05), reflecting improved muscle mass. At t(3m),
      a significant increase in spontaneous physical activity (from 45% to 71%,
      compared with baseline data of control children, P <.05) and physical capacity
      (from 31%-78%, P <.01) was found. CONCLUSIONS: In persons with PWS, a well
      defined and easy-to-accomplish training program improves local body composition
      and has generalized effects on physical activity and capacity, opening up a new
      therapeutic option to improve metabolic conditions.

PMID- 12520258
TI  - Sunburn reduction through parental role modeling and sunscreen vigilance.
AB  - OBJECTIVES: To identify characteristics associated with child sunburn experience
      and sun protection practices, including parent and child demographics, phenotype,
      and sun-related knowledge, attitudes, and behaviors. STUDY DESIGN: A nationally
      representative telephone survey conducted in 1999 with 651 parents of children 5
      to 12 years of age to collect data relating to the sun-related knowledge,
      attitudes, and behaviors of the parent and child. RESULTS: Nearly half of parents
      (49%) and children (44%) were sunburnt during the previous summer. Parents who
      reported that they had been sunburnt were more likely to have children who had
      been sunburnt (OR = 2.9, 95% CI = 2.0, 4.2). Conversely, parents with a high
      level of sun protection behavior were less likely to report being sunburnt (OR =
      0.6, 95% CI = 0.4, 0.9), and their children were more likely to have a high level
      of sun protection behavior (OR = 3.0, 95% CI = 2.0, 4.6) and sunscreen vigilance
      (OR = 2.7, 95% CI = 1.7, 4.5). High sunscreen vigilance was associated with a 60%
      reduction in child sunburning. CONCLUSIONS: The sunburn experience and sun
      protection practices of children (5-12 years of age) are closely linked to a
      number of modifiable attitudes and behaviors of their parents. Therefore the
      inclusion of parents and care givers in interventions targeting children may
      increase program efficacy.

PMID- 12520260
TI  - Transient elevation in risk of injury in siblings following injury encounters.
AB  - OBJECTIVE: To examine patterns of injury risk within sibling groups to determine
      whether a clinical encounter for injury care could be used as a marker to
      identify siblings at high risk for subsequent injury. STUDY DESIGN: Children (n =
      16,335; 0-15 years of age) enrolled in a health maintenance organization between
      1995 and 1997 contributed 38,215 child-years of data. We tracked medically
      treated injuries that were diagnosed and classified as unintentional. Incidence
      rates and hazard ratios were calculated for children whose sibling had been
      injured in the previous 180 days compared with children without such exposure,
      adjusted for age, sex, sibling group size, and noninjury health care utilization.
      RESULTS: The 5,851 children had a total of 8,973 injuries. Injury incidence was
      319 per 1,000 child-years among children with recent sibling injury and 235 per
      1,000 child-years among children without this exposure (relative risk, 1.44; 95%
      CI, 1.36-1.53). When minor injuries were excluded, the adjusted relative risk was
      1.95 (95% CI, 1.54-2.47). CONCLUSIONS: Injury risk is shared within sibling
      groups and varies according to recent sibling injury experience. Clinical
      encounters for injury care might be used to identify sibling groups at increased
      injury risk.

PMID- 12520261
TI  - Usefulness of helical CT angiography and MRI in the diagnosis and treatment of
      pentalogy of Cantrell.

PMID- 12520262
TI  - Malaria after the genome.

PMID- 12520263
TI  - Los Alamos directors resign after row over sacked whistleblowers.

PMID- 12520264
TI  - Insurers left reeling by disaster year.

PMID- 12520265
TI  - US societies unite in plea for boost to research budgets.

PMID- 12520266
TI  - British chemists warned of impending stagnation.

PMID- 12520267
TI  - China plans clean sweep on dust storms.

PMID- 12520268
TI  - Indian prime minister pledges to revamp science.

PMID- 12520269
TI  - Comet mission hangs in the balance.

PMID- 12520270
TI  - NSF urged to take multidisciplinary tack on environment.

PMID- 12520271
TI  - Biologists seek blueprint for international stem-cell effort.

PMID- 12520273
TI  - Bioterrorism: Agriculture shock.

PMID- 12520274
TI  - Climate change: The oresmen.

PMID- 12520275
TI  - Strict guidelines make it clear who's responsible.

PMID- 12520276
TI  - Funding should recognize the value of peer review.

PMID- 12520277
TI  - Biology can be helpful to open-minded physicists.

PMID- 12520282
TI  - Synthetic biology: Act natural.

PMID- 12520283
TI  - Planetary science: Model for magnetic mystery.

PMID- 12520284
TI  - Developmental biology: A larval revelation.

PMID- 12520285
TI  - Global change: Leads, lags and the tropics.

PMID- 12520288
TI  - Materials science: Bursting apart.

PMID- 12520286
TI  - Molecular systematics: Counting angels with DNA.

PMID- 12520289
TI  - Physiology: Cost-free longevity in mice?

PMID- 12520290
TI  - Atomic-force microscopy: Rhodopsin dimers in native disc membranes.

PMID- 12520291
TI  - Coulomb fission: Rayleigh jets from levitated microdroplets.

PMID- 12520292
TI  - Econophysics: Master curve for price-impact function.

PMID- 12520293
TI  - Econophysics: Two-phase behaviour of financial markets.

PMID- 12520294
TI  - Continuing emissions of methyl chloroform from Europe.
AB  - The consumption of methyl chloroform (1,1,1-trichloroethane), an industrial
      solvent, has been banned by the 1987 Montreal Protocol because of its ozone
      depleting potential. During the 1990s, global emissions have decreased
      substantially and, since 1999, near-zero emissions have been estimated for Europe
      and the United States. Here we present measurements of methyl chloroform that are
      inconsistent with the assumption of small emissions. Using a tracer transport
      model, we estimate that European emissions were greater than 20 Gg in 2000.
      Although these emissions are not significant for stratospheric ozone depletion,
      they have important implications for estimates of global tropospheric hydroxyl
      radical (OH) concentrations, deduced from measurements of methyl chloroform.
      Ongoing emissions therefore cast doubt upon recent reports of a strong and
      unexpected negative trend in OH during the 1990s and a previously calculated
      higher OH abundance in the Southern Hemisphere compared to the Northern
      Hemisphere.

PMID- 12520295
TI  - An early lunar core dynamo driven by thermochemical mantle convection.
AB  - Although the Moon currently has no internally generated magnetic field,
      palaeomagnetic data, combined with radiometric ages of Apollo samples, provide
      evidence for such a magnetic field from approximately 3.9 to 3.6 billion years
      (Gyr) ago, possibly owing to an ancient lunar dynamo. But the presence of a lunar
      dynamo during this time period is difficult to explain, because thermal evolution
      models for the Moon yield insufficient core heat flux to power a dynamo after
      approximately 4.2 Gyr ago. Here we show that a transient increase in core heat
      flux after an overturn of an initially stratified lunar mantle might explain the
      existence and timing of an early lunar dynamo. Using a three-dimensional
      spherical convection model, we show that a dense layer, enriched in radioactive
      elements (a 'thermal blanket'), at the base of the lunar mantle can initially
      prevent core cooling, thereby inhibiting core convection and magnetic field
      generation. Subsequent radioactive heating progressively increases the buoyancy
      of the thermal blanket, ultimately causing it to rise back into the mantle. The
      removal of the thermal blanket, proposed to explain the eruption of thorium- and
      titanium-rich lunar mare basalts, plausibly results in a core heat flux
      sufficient to power a short-lived lunar dynamo.

PMID- 12520296
TI  - Measuring intense rotation and dissipation in turbulent flows.
AB  - Turbulent flows are highly intermittent--for example, they exhibit intense bursts
      of vorticity and strain. Kolmogorov theory describes such behaviour in the form
      of energy cascades from large to small spatial and temporal scales, where energy
      is dissipated as heat. But the causes of high intermittency in turbulence, which
      show non-gaussian statistics, are not well understood. Such intermittency can be
      important, for example, for enhancing the mixing of chemicals, by producing sharp
      drops in local pressure that can induce cavitation (damaging mechanical
      components and biological organisms), and by causing intense vortices in
      atmospheric flows. Here we present observations of the three components of
      velocity and all nine velocity gradients within a small volume, which allow us to
      determine simultaneously the dissipation (a measure of strain) and enstrophy (a
      measure of rotational energy) of a turbulent flow. Combining the statistics of
      all measurements and the evolution of individual bursts, we find that a typical
      sequence for intense events begins with rapid strain growth, followed by rising
      vorticity and a final sudden decline in stretching. We suggest two mechanisms
      which can produce these characteristics, depending whether they are due to the
      advection of coherent structures through our observed volume or caused locally.

PMID- 12520297
TI  - Observation of surface and bulk phase transitions in nematic liquid crystals.
AB  - The behaviour of liquid crystal (LC) molecules near a surface is of both
      fundamental and technological interest: it gives rise to various surface phase
      transition and wetting phenomena, and surface-induced ordering of the LC
      molecules is integral to the operation of LC displays. Here we report the
      observation of a pure isotropic-nematic (IN) surface phase transition-clearly
      separated from the bulk IN transition-in a nematic LC on a substrate. Differences
      in phase behaviour between surface and bulk are expected, but have hitherto
      proved difficult to distinguish, owing in part to the close proximity of their
      transition temperatures. We have overcome these difficulties by using a mixture
      of nematic LCs: small, surface-induced composition variations lead to complete
      separation of the surface and bulk transitions, which we then study independently
      as a function of substrate and applied magnetic field. We find the surface IN
      transition to be of first order on surfaces with a weak anchoring energy and
      continuous on surfaces with a strong anchoring. We show that the presence of high
      magnetic fields does not change the surface IN transition temperature, whereas
      the bulk IN transition temperature increases with field. We attribute this to the
      interaction energy between the surface and bulk phases, which is tuned by
      magnetic-field-induced order in the surface-wetting layer.

PMID- 12520298
TI  - Magnitude and timing of temperature change in the Indo-Pacific warm pool during
      deglaciation.
AB  - Ocean-atmosphere interactions in the tropical Pacific region have a strong
      influence on global heat and water vapour transport and thus constitute an
      important component of the climate system. Changes in sea surface temperatures
      and convection in the tropical Indo-Pacific region are thought to be responsible
      for the interannual to decadal climate variability observed in extra-tropical
      regions, but the role of the tropics in climate changes on millennial and orbital
      timescales is less clear. Here we analyse oxygen isotopes and Mg/Ca ratios of
      foraminiferal shells from the Makassar strait in the heart of the Indo-Pacific
      warm pool, to obtain synchronous estimates of sea surface temperatures and ice
      volume. We find that sea surface temperatures increased by 3.5-4.0 degrees C
      during the last two glacial-interglacial transitions, synchronous with the global
      increase in atmospheric CO2 and Antarctic warming, but the temperature increase
      occurred 2,000-3,000 years before the Northern Hemisphere ice sheets melted. Our
      observations suggest that the tropical Pacific region plays an important role in
      driving glacial-interglacial cycles, possibly through a system similar to how El
      Nino/Southern Oscillation regulates the poleward flux of heat and water vapour.

PMID- 12520299
TI  - Group decision-making in animals.
AB  - Groups of animals often need to make communal decisions, for example about which
      activities to perform, when to perform them and which direction to travel in;
      however, little is known about how they do so. Here, we model the fitness
      consequences of two possible decision-making mechanisms: 'despotism' and
      'democracy'. We show that under most conditions, the costs to subordinate group
      members, and to the group as a whole, are considerably higher for despotic than
      for democratic decisions. Even when the despot is the most experienced group
      member, it only pays other members to accept its decision when group size is
      small and the difference in information is large. Democratic decisions are more
      beneficial primarily because they tend to produce less extreme decisions, rather
      than because each individual has an influence on the decision per se. Our model
      suggests that democracy should be widespread and makes quantitative, testable
      predictions about group decision-making in non-humans.

PMID- 12520300
TI  - Larval stages of a living sea lily (stalked crinoid echinoderm).
AB  - The embryos and larvae of stalked crinoids, which are considered the most basal
      group of extant echinoderms, have not previously been described. In contrast,
      much is known about the development of the more accessible stalkless crinoids
      (feather stars), which are phylogenetically derived from stalked forms. Here we
      describe the development of a sea lily from fertilization to larval settlement.
      There are two successive larval stages: the first is a non-feeding auricularia
      stage with partly longitudinal ciliary bands (similar to the auricularia and
      bipinnaria larvae of holothurian and asteroid echinoderms, respectively); the
      second is a doliolaria larva with circumferential ciliary bands (similar to the
      earliest larval stage of stalkless crinoids). We suggest that a dipleurula-type
      larva is primitive for echinoderms and is the starting point for the evolution of
      additional larval forms within the phylum. From a wider evolutionary viewpoint,
      the demonstration that the most basal kind of echinoderm larva is a dipleurula is
      consistent with Garstang's auricularia theory for the phylogenetic origin of the
      chordate neural tube.

PMID- 12520301
TI  - Robust judgement of inter-object distance by an arthropod.
AB  - Animals use several strategies for depth vision, reflecting the constraints
      imposed by body size, the structure of the visual system and the visual geometry
      of the environment. Arthropods in particular have restricted depth perception,
      because they are small and possess closely set, low-resolution compound eyes.
      Yet, here we show that fiddler crabs defending their burrows from conspecifics
      can judge how close other crabs are to their burrow. When confronted with small
      dummy crabs, the burrow owners assess the dummy's position and motion relative to
      their burrow and not relative to themselves--in other words, by using an
      allocentric rather than an egocentric frame of reference. Irrespective of their
      own distance from the dummy, the likelihood that the crabs rush back to defend
      their burrow increases strongly as the dummy approaches the burrow. In addition,
      the mean dummy-burrow distance at which the crabs respond is constant and
      independent of the dummy's direction of approach. We propose that to solve this
      sophisticated task of relative distance judgement, the crabs combine visual
      information on dummy position and direction with information on burrow location
      acquired during path integration. In doing so, the crabs, like humans, make
      clever use of the visual geometry of their environment.

PMID- 12520302
TI  - An active DNA transposon family in rice.
AB  - The publication of draft sequences for the two subspecies of Oryza sativa (rice),
      japonica (cv. Nipponbare) and indica (cv. 93-11), provides a unique opportunity
      to study the dynamics of transposable elements in this important crop plant. Here
      we report the use of these sequences in a computational approach to identify the
      first active DNA transposons from rice and the first active miniature inverted
      repeat transposable element (MITE) from any organism. A sequence classified as a
      Tourist-like MITE of 430 base pairs, called miniature Ping (mPing), was present
      in about 70 copies in Nipponbare and in about 14 copies in 93-11. These mPing
      elements, which are all nearly identical, transpose actively in an indica cell
      culture line. Database searches identified a family of related transposase
      encoding elements (called Pong), which also transpose actively in the same cells.
      Virtually all new insertions of mPing and Pong elements were into low-copy
      regions of the rice genome. Since the domestication of rice mPing MITEs have been
      amplified preferentially in cultivars adapted to environmental extremes-a
      situation that is reminiscent of the genomic shock theory for transposon
      activation.

PMID- 12520303
TI  - The plant MITE mPing is mobilized in anther culture.
AB  - Transposable elements constitute a large portion of eukaryotic genomes and
      contribute to their evolution and diversification. Miniature inverted-repeat
      transposable elements (MITEs) constitute one of the main groups of transposable
      elements and are distributed ubiquitously in the genomes of plants and animals
      such as maize, rice, Arabidopsis, human, insect and nematode. Because active
      MITEs have not been identified, the transposition mechanism of MITEs and their
      accumulation in eukaryotic genomes remain poorly understood. Here we describe a
      new class of MITE, called miniature Ping (mPing), in the genome of Oryza sativa
      (rice). mPing elements are activated in cells derived from anther culture, where
      they are excised efficiently from original sites and reinserted into new loci. An
      mPing-associated Ping element, which has a putative PIF family transposase, is
      implicated in the recent proliferation of this MITE family in a subspecies of
      rice.

PMID- 12520304
TI  - Mobilization of a transposon in the rice genome.
AB  - Rice (Oryza sativa L.) is an important crop worldwide and, with the availability
      of the draft sequence, a useful model for analysing the genome structure of
      grasses. To practice efficient rice breeding through genetic engineering
      techniques, it is important to identify the economically important genes in this
      crop. The use of mobile transposons as gene tags in intact plants is a powerful
      tool for functional analysis because transposon insertions often inactivate
      genes. Here we identify an active rice transposon named miniature Ping (mPing)
      through analysis of the mutability of a slender mutation of the glume-the seed
      structure that encloses and determines the shape of the grain. The mPing
      transposon is inserted in the slender glume (slg) mutant allele but not in the
      wild-type allele. Search of the O. sativa variety Nipponbare genome identified 34
      sequences with high nucleotide similarity to mPing, indicating that mPing
      constitutes a family of transposon elements. Excision of mPing from slg plants
      results in reversion to a wild-type phenotype. The mobility of the transposon
      mPing in intact rice plants represents a useful alternative tool for the
      functional analysis of rice genes.

PMID- 12520305
TI  - Intracardiac fluid forces are an essential epigenetic factor for embryonic
      cardiogenesis.
AB  - The pattern of blood flow in the developing heart has long been proposed to play
      a significant role in cardiac morphogenesis. In response to flow-induced forces,
      cultured cardiac endothelial cells rearrange their cytoskeletal structure and
      change their gene expression profiles. To link such in vitro data to the intact
      heart, we performed quantitative in vivo analyses of intracardiac flow forces in
      zebrafish embryos. Using in vivo imaging, here we show the presence of high
      shear, vortical flow at two key stages in the developing heart, and predict flow
      induced forces much greater than might have been expected for micro-scale
      structures at low Reynolds numbers. To test the relevance of these shear forces
      in vivo, flow was occluded at either the cardiac inflow or outflow tracts,
      resulting in hearts with an abnormal third chamber, diminished looping and
      impaired valve formation. The similarity of these defects to those observed in
      some congenital heart diseases argues for the importance of intracardiac
      haemodynamics as a key epigenetic factor in embryonic cardiogenesis.

PMID- 12520306
TI  - Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the
      transcription factor Ste12.
AB  - The budding yeast Saccharomyces cerevisiae differentiates into filamentous
      invasively growing forms under conditions of nutrient limitation. This response
      is dependent on the transcription factor Ste12 and on the mating pheromone
      response mitogen-activated protein (MAP) kinase cascade, but a mechanism for
      regulation of Ste12 by nutrient limitation has not been defined. Here we show
      that Ste12 function in filamentous growth is regulated by the cyclin-dependent
      kinase Srb10 (also known as Cdk8), which is associated with the RNA polymerase II
      holoenzyme. Srb10 inhibits filamentous growth in cells growing in rich medium by
      phosphorylating Ste12 and decreasing its stability. Under conditions of limiting
      nitrogen, loss of Srb10 protein and kinase activity occurs, with a corresponding
      loss of Ste12 phosphorylation. Mutation of the Srb10-dependent phosphorylation
      sites increases pseudohyphal development but has no effect on the pheromone
      response of haploid yeast. Srb10 kinase activity is also regulated independently
      of the mating pheromone-response pathway. This indicates that Srb10 controls
      Ste12 activity for filamentous growth in response to nitrogen limitation and is
      consistent with the hypothesis that Srb10 regulates gene-specific activators in
      response to physiological signals to coordinate gene expression with growth
      potential.

PMID- 12520310
TI  - Sweet dreams.

PMID- 12520311
TI  - Seeking strength in numbers.

PMID- 12520312
TI  - D1-receptor drugs and cocaine-seeking behavior: investigation of receptor
      mediation and behavioral disruption in rats.
AB  - RATIONALE: Dopamine D1-receptor antagonists and agonists both attenuate cocaine
      seeking behavior (i.e., operant responding in the absence of cocaine
      reinforcement) elicited by a cocaine prime or cocaine-paired stimuli. It remains
      unclear whether these effects are D1-receptor mediated. OBJECTIVES: The present
      study tested whether a D1 antagonist (SCH-23390) would reverse the attenuating
      effects of a D1 agonist (SKF-81297) on cocaine-seeking behavior and whether
      behavioral disruption is involved in these effects. METHODS: Rats trained to
      press a lever for cocaine reinforcement with light and tone cues paired with each
      infusion underwent daily extinction sessions during which responding had no
      scheduled consequences (i.e., neither cocaine nor the cocaine-paired stimulus
      complex was available). After responding diminished, the effects of the D1
      antagonist on the dose-response functions of the D1 agonist for reinstatement of
      cocaine-seeking behavior by response-contingent cue presentations or cocaine
      priming were examined. A separate experiment assessed the effects of the agonist
      on the dose-response function of the antagonist for cue reinstatement.
      Stereotyped behavior and activity were also measured during each test session.
      RESULTS: The attenuating effects of SKF-81297 on cocaine-seeking behavior during
      cocaine-primed reinstatement were reversed by co-administration of SCH-23390.
      However, no evidence for reversal of the attenuation during cue reinstatement was
      found even though agonist-induced stereotypy and antagonist-induced hypoactivity
      were reversed by co-administration of the two drugs during the same test session.
      CONCLUSIONS: The findings suggest that the attenuating effects of D1-receptor
      drugs on cocaine-seeking behavior during cocaine reinstatement are mediated by
      dopamine D1 receptors; however, it remains unclear whether the effects of these
      drugs on cocaine-seeking behavior during cue reinstatement are D1-receptor
      mediated. Nevertheless, it is evident that the attenuation of cocaine-seeking
      behavior by these drugs is not simply due to behavioral disruption.

PMID- 12520313
TI  - Neuroendocrine and behavioral responses to dopaminergic agonists in adolescents
      with alcohol abuse.
AB  - RATIONALE: Dopaminergic systems are involved in the pathophysiology of alcohol
      use disorders, but there is little research investigating the role of these
      systems in adolescents. OBJECTIVES: In this study, we investigated dopaminergic
      systems in adolescents with alcohol abuse by determining neuroendocrine and
      behavioral responses to dopaminergic drug challenges. METHODS: Twenty-six
      participants (11 with DSM IV alcohol abuse and 15 controls) were enrolled in the
      study. Neuroendocrine and behavioral response to the dopaminergic indirect
      agonist methylphenidate (10 mg) and the direct agonist pergolide (50 mcg), were
      examined. The primary response measures were spontaneous eye-blink rate, plasma
      prolactin (PRL), and growth hormone (GH). Additionally, participants completed a
      visual analog mood scale (VAMS). RESULTS: The rate of increase in plasma GH level
      was blunted for adolescents with alcohol abuse compared to the control group,
      after methylphenidate administration [ t=-2.75, P=0.0066, 95% confidence interval
      (CI) -0.3, -0.048]. The rate of decrease in PRL level after pergolide
      administration was greater in adolescents with alcohol abuse as compared to the
      control group ( t=-3.05, P=0.0028, 95% CI -0.01923, -0.00409). Adolescents with
      alcohol abuse rated themselves as less "energized" in comparison to the control
      group after methylphenidate (rate difference=-0.4, P=0.0231). CONCLUSIONS: This
      preliminary study suggests that adolescents with alcohol abuse may have a
      differential response to dopaminergic agonists, as also reported for adults with
      alcohol use disorders. Further studies investigating gender differences, and
      other neurotransmitter systems are needed to understand the differential
      dopaminergic response in adolescents with alcohol use disorders.

PMID- 12520315
TI  - Spinal hematoma: a literature survey with meta-analysis of 613 patients.

PMID- 12520314
TI  - Spinal hematoma: a literature survey with meta-analysis of 613 patients.
AB  - Spinal hematoma has been described in autopsies since 1682 and as a clinical
      diagnosis since 1867. It is a rare and usually severe neurological disorder that,
      without adequate treatment, often leads to death or permanent neurological
      deficit. Epidural as well as subdural and subarachnoid hematomas have been
      investigated. Some cases of subarachnoid spinal hematoma may present with
      symptoms similar to those of cerebral hemorrhage. The literature offers no
      reliable estimates of the incidence of spinal hematoma, perhaps due to the rarity
      of this disorder. In the present work, 613 case studies published between 1826
      and 1996 have been evaluated, which represents the largest review on this topic
      to date. Most cases of spinal hematoma have a multifactorial etiology whose
      individual components are not all understood in detail. In up to a third of cases
      (29.7%) of spinal hematoma, no etiological factor can be identified as the cause
      of the bleeding. Following idiopathic spinal hematoma, cases related to
      anticoagulant therapy and vascular malformations represent the second and third
      most common categories. Spinal and epidural anesthetic procedures in combination
      with anticoagulant therapy represent the fifth most common etiological group and
      spinal and epidural anesthetic procedures alone represent the tenth most common
      cause of spinal hematoma. Anticoagulant therapy alone probably does not trigger
      spinal hemorrhage. It is likely that there must additionally be a "locus minoris
      resistentiae" together with increased pressure in the interior vertebral venous
      plexus in order to cause spinal hemorrhage. The latter two factors are thought to
      be sufficient to cause spontaneous spinal hematoma. Physicians should require
      strict indications for the use of spinal anesthetic procedures in patients
      receiving anticoagulant therapy, even if the incidence of spinal hematoma
      following this combination is low. If spinal anesthetic procedures are performed
      before, during, or after anticoagulant treatment, close monitoring of the
      neurological status of the patient is warranted. Time limits regarding the use of
      anticoagulant therapy before or after spinal anesthetic procedures have been
      proposed and are thought to be safe for patients. Investigation of the
      coagulation status alone does not necessarily provide an accurate estimate of the
      risk of hemorrhage. The most important measure for recognizing patients at high
      risk is a thorough clinical history. Most spinal hematomas are localized dorsally
      to the spinal cord at the level of the cervicothoracic and thoracolumbar regions.
      Subarachnoid hematomas can extend along the entire length of the subarachnoid
      space. Epidural and subdural spinal hematoma present with intense, knife-like
      pain at the location of the hemorrhage ("coup de poignard") that may be followed
      in some cases by a pain-free interval of minutes to days, after which there is
      progressive paralysis below the affected spinal level. Subarachnoid hematoma can
      be associated with meningitis symptoms, disturbances of consciousness, and
      epileptic seizures and is often misdiagnosed as cerebral hemorrhage based on
      these symptoms. Most patients are between 55 and 70 years old. Of all patients
      with spinal hemorrhage, 63.9% are men. The examination of first choice is
      magnetic resonance imaging. The treatment of choice is surgical decompression. Of
      the patients investigated in the present work, 39.6% experienced complete
      recovery. The less severe the preoperative symptoms are and the more quickly
      surgical decompression can be performed, the better are the chances for complete
      recovery. It is therefore essential to recognize the relatively typical clinical
      presentation of spinal hematoma in a timely manner to allow correct diagnostic
      and therapeutic measures to be taken to maximize the patient's chance of complete
      recovery.

PMID- 12520316
TI  - Spinal hematoma: a literature survey with meta-analysis of 613 patients.

PMID- 12520317
TI  - Spinal hematoma: a literature survey with meta-analysis of 613 patients.

PMID- 12520318
TI  - Frame-based and frameless stereotaxy in the localization of cavernous angiomas.
AB  - Cavernous angiomas are mostly small intracranial vascular lesions which can be
      intraoperatively localized by sonography or stereotactic methods. This paper
      compares the results of cavernous angioma surgery localized by frame-based vs
      frameless techniques. Thirty-nine patients with cortical or subcortical lobar
      cavernoma were operated on by a microsurgical trans-sulcal approach. The
      localization of the lesion was performed in 19 (49%) patients by frame-based
      technique and in 20 (51%) patients by frameless navigation. In 22 (56%) of the
      patients, the cavernomas were located in an eloquent cortical area. Ten of 22 of
      these lesions were localized by frame-based stereotaxy and 12/22 by frameless
      navigation. The patients demonstrated the following preoperative symptoms:
      seizures 20 (51%), hemorrhage 18 (46%), focal neurologic deficit 11 (28%), and
      headache three (7%), and three (7%) were asymptomatic. Thirteen of 19 patients
      localized with frame-based stereotaxy were postoperatively asymptomatic or their
      preoperative neurological symptoms improved. Four of 19 had a transitory
      neurologic deficit and 2/19 a permanent worsening. Seventeen of 20 patients
      localized by frameless navigation were asymptomatic or neurologically improved.
      Three out of 20 suffered from a transient neurologic deficit. Regarding the
      seizures, 14 (70%) patients were postoperatively free of seizures, three (15%)
      were improved, and three (15%) were unchanged. The frameless navigation was
      superior regarding the flexibility for approaches along the skull base and
      midline, and the frame-based method was superior regarding the accuracy for very
      small lesions (less than 7 mm). In other cases, both methods were equal. Frame
      based and frameless stereotactic methods are useful in the localization of small
      cavernous angiomas. They make it possible to remove cavernous angiomas in
      eloquent cortical regions with low risk of a permanent neurologic deficit.

PMID- 12520319
TI  - Intraoperative management of cystic meningiomas.
AB  - Cystic meningiomas are uncommon tumors that are easily confused with metastatic
      or glial tumors with cystic components. We report on our experience of
      intraoperative findings and management of peritumoral cyst wall and cyst fluid in
      cystic meningiomas. We reviewed all the meningiomas operated on at our department
      in a 3 1/2-year period (January 1998 to June 2001). Pathological and
      intraoperative findings of cystic meningiomas compared to noncystic meningiomas
      are examined. There were 111 cases of intracranial meningiomas operated on,
      including seven cystic meningiomas (6.3%). In six cases, we found peritumoral
      cyst configurations. The tumor locations of cystic meningiomas were the cerebral
      convexity and sphenoid ridge. One peritumoral cyst formation had meningioma cells
      in the cyst wall. Cytologic examination of the cystic fluid displayed the
      presence of meningiothelial cells in one case. In one case, intraoperative
      findings and pathological examination provided the diagnosis of two differently
      located meningiomas in one cyst configuration, its walls lined by clear
      arachnoid. Four of the seven cases had peritumoral cystic meningiomas of the
      atypical type according to the WHO classification. One case with intratumoral
      cyst configuration was associated with the anaplastic type (WHO degrees 3).
      Intraoperative biopsies and histopathological studies of the cyst wall are
      recommended in peritumoral cystic meningiomas. Our observations suggest that
      cystic meningiomas have the potential to spread through cystic fluid to the
      cystic wall in peritumoral cyst configuration. The follow-up intervals should be
      short in cystic meningiomas.

PMID- 12520320
TI  - Acute phase effects of ATP-MgCl2 on experimental spinal cord injury.
AB  - The purpose of this study was to study the acute phase effects of adenosine
      triphosphate (ATP)-MgCl2 on experimental spinal cord clip compression injury.
      Spinal cord clip compression injury was performed on 36 albino Wistar rats. The
      rats were divided into five groups. T4-T8 total laminectomy was performed on all
      rats. Group 1: sham-operated group. Group 2: clip compression group. In group 3,
      ATP-MgCl2 (100 micro mol/kg) was given 2 min before the "clip compression
      injury." In group 4, ATP-MgCl2 (100 micro mol/kg) was given 5 min after the clip
      compression injury. In group 5, ATP MgCl2 (100 micro mol/kg) was administered 8 h
      after the injury. The spinal cords were excised for a length of 2 cm and deep
      frozen at -76 degrees C. Tissue malondialdehyde (MDA) levels were used to
      determine the effects of ATP-MgCl2 on spinal cord lipid peroxidation. In the
      groups in which ATP MgCl2 was administered after the clip compression injury
      (groups 4 and 5), the decrease in spinal cord MDA levels was statistically
      significant when compared with those of the injury group (group 2). Although MDA
      levels of group 4 were lower than those of group 5, this difference was not
      statistically significant. Administration of the ATP-MgCl2 before the clip
      compression injury (in group 3) did not have a statistically significant effect
      on lipid peroxidation when compared with the injury group (group 2). In this
      study, we found that ATP-MgCl2 has decreased lipid peroxidation in spinal cord
      injury and protected the spinal cord from secondary injury after the trauma. We
      concluded that ATP-MgCl2 may be used in the treatment of spinal cord injuries in
      conjunction with the other treatment modalities, but further investigations are
      mandatory.

PMID- 12520323
TI  - "What goes up must immediately come down!" Which indication for short-acting
      nifedipine in children with arterial hypertension?

PMID- 12520324
TI  - Does growth hormone treatment affect the risk of post-transplant renal cancer?
AB  - According to the analysis of the Collaborative Transplant Study (CTS), the
      incidence of renal carcinoma in patients with renal transplantation as well as
      with heart transplantation is significantly increased at any given patient age.
      The cumulative incidence 10 years after kidney transplantation is 185 per 100,000
      patients in children below the age of 19 years at the time of transplantation.
      Age and immunosuppressive treatment seem to be the major risk factors. The
      majority of cancers develop within the native kidneys. Chronic transplant
      nephropathy and accelerated senescence may be further risk factors for the
      development of cancer within a kidney transplant. Growth hormone (GH) treatment
      could not be identified as an additional risk factor.

PMID- 12520325
TI  - Why is the oncogene WT1 in the developing kidney and what is it doing there?

PMID- 12520326
TI  - The plasma membrane proton pump ATPase: the significance of gene subfamilies.
AB  - The plasma membrane proton pump ATPase (H(+)-ATPase) plays a central role in
      transport across the plasma membrane. As a primary transporter, it mediates ATP
      dependent H(+) extrusion to the extracellular space, thus creating pH and
      potential differences across the plasma membrane that activate a large set of
      secondary transporters. In several species, the H(+)-ATPase is encoded by a
      family of approximately 10 genes, classified into 5 gene subfamilies and we might
      ask what can this tell us about the concept, and the evolution, of gene families
      in plants. All the highly expressed H(+)-ATPase genes are classified into only
      two gene subfamilies, which diverged before the emergence of present plant
      species, raising the questions of the significance of the existence of these two
      well-conserved subfamilies and whether this is related to different kinetic or
      regulatory properties. Finally, what can we learn from experimental approaches
      that silence specific genes? In this review, we would like to discuss these
      questions in the light of recent data.

PMID- 12520327
TI  - Light interacts with auxin during leaf elongation and leaf angle development in
      young corn seedlings.
AB  - Modern corn ( Zea mays L.) varieties have been selected for their ability to
      maintain productivity in dense plantings. We have tested the possibility that the
      physiological consequence of the selection of the modern hybrid, 3394, for
      increased crop yield includes changes in responsiveness to auxin and light.
      Etiolated seedlings in the modern line are shorter than in an older hybrid, 307,
      since they produce shorter coleoptile, mesocotyl, and leaves (blade as well as
      sheath). Etiolated 3394 seedlings, as well as isolated mesocotyl and sheath
      segments, were less responsive to auxin and an inhibitor of polar auxin
      transport, N-1-naphthylphthalamic acid (NPA). Reduced response of 3394 to auxin
      was associated with less reduction of elongation growth by light (white, red, far
      red, blue) than in 307, whereas the activity of polar auxin transport (PAT) and
      its reduction by red or far-red light was similar in both genotypes. NPA reduced
      PAT in etiolated 3394 seedlings much less than in 307. A characteristic feature
      of 3394 plants is more erect leaves. In both hybrids, light (white, red, blue)
      increases leaf declination from the vertical, whereas NPA reduces leaf
      declination in 307, but not in 3394. Our results support findings that auxin and
      PAT are involved in elongation growth of corn seedlings, and we show that light
      interacts with auxin or PAT in regulation of leaf declination. We hypothesize
      that, relative to 307, more erect leaves in the modern hybrid may be primarily a
      consequence of a reduced amount of auxin receptor(s) and reduced responsiveness
      to light in etiolated 3394 plants. The more erect leaves in 3394 may contribute
      to the tolerance of the modern corn hybrid to dense planting.

PMID- 12520328
TI  - Molecular characterization of two plant BI-1 homologues which suppress Bax
      induced apoptosis in human 293 cells.
AB  - To date, few homologues of animal programmed cell death (PCD) regulators have
      been identified in plants. Among these is the plant Bax Inhibitor-1 (BI-1)
      protein, which possesses, like its human counterpart, the ability to suppress Bax
      induced lethality in yeast cells. As the role of BI-1 in the regulation of plant
      PCD remains to be elucidated, we cloned BnBI-1 and NtBI-1 from cDNA libraries of
      oilseed rape ( Brassica napus L.) and tobacco ( Nicotiana tabacum L.). The
      analysis of the deduced amino acid sequences of BnBI-1 and NtBI-1 indicated that
      these proteins share a relatively high level of identity with other plant BI-1
      proteins (73-95%) as well as with animal BI-1 proteins (26-42%). Comparative
      analysis with other available plant BI-1 proteins allowed the establishment of a
      structural model presenting seven transmembrane domains. Moreover, transient co
      transfection of Bax with BnBI-1 or NtBI-1 in human embryonic kidney 293 cells
      revealed that both proteins can substantially inhibit apoptosis induced by Bax
      overexpression. Localization studies were also conducted using stable
      transformation of tobacco BY-2 cells and Saccharomyces cerevisiae, or transient
      expression in tobacco leaves, with the fusion protein BnBI-1GFP under control of
      the cauliflower mosaic virus 35S promoter. All transformants showed a
      fluorescence pattern of distribution typical of an endoplasmic reticulum (ER)
      protein. Results from differential permeabilization experiments in BY-2 cells
      expressing BnBI-1GFP also showed that the C-terminus is located on the cytosolic
      side of the ER. Taken altogether, our results suggest that BI-1 is evolutionarily
      conserved and could act as a key regulator of a death pathway common to plants
      and animals.

PMID- 12520329
TI  - Identification of the pepper SAR8.2 gene as a molecular marker for pathogen
      infection, abiotic elicitors and environmental stresses in Capsicum annuum.
AB  - Pepper ( Capsicum annuum L.) SAR8.2 genes, designated CASAR82A, B and C, which
      are induced by all the biotic and abiotic stresses, were isolated from a pepper
      cDNA library constructed with the mRNAs from pepper plants infected with
      Xanthomonas campestris pv. vesicatoria. The pepper CASAR82A, B and C gene
      products, which are very similar to each other in amino acid sequences, have 43
      50% homology with those of tobacco SAR8.2 genes. The CASAR8.2 genes were not
      constitutively expressed in any of the organs of healthy pepper plants. In
      contrast, the CASAR82A gene was locally or systemically induced in pepper plants
      infected by X. campestris pv. vesicatoria, Colletotrichum coccodes or
      Phytophthora capsici. Strong induction of the CASAR82A gene also was found in
      pepper leaves treated with ethylene, methyl jasmonate, indole-3-acetic acid,
      abscisic acid, salicylic acid, benzothiadiazole, DL-beta- n-amino butyric acid or
      hydrogen peroxide. Interestingly, the transcription of the CASAR82A gene was
      rapidly triggered by high salinity, drought or low-temperature stresses, but not
      by mechanical wounding. In situ hybridization results revealed that the CASAR82A
      mRNAs were localized in phloem and epidermal cells of pepper leaf and stem
      tissues infected by C. coccodes and P. capsici, or treated with salicylic acid.
      These results thus suggest that pepper SAR8.2 genes may be valuable as a
      molecular marker for the detection of various pathogen infections, abiotic
      elicitors and environmental stresses.

PMID- 12520330
TI  - Rapid increase of vacuolar volume in response to salt stress.
AB  - Suspension-cultured cells of mangrove [Bruguiera sexangula (Lour.) Poir.] showed
      a rapid increase in vacuolar volume under salt stress, although there was no
      change in the cell volume. The rapid increase in the vacuolar volume was an
      active process, which followed the activation of the tonoplast H(+)-ATPase and
      the vacuolar acid phosphatase. The same phenomenon was observed in barley
      (Hordeum vulgare L. cv. Doriru) root meristematic cells under salt stress but not
      in pea ( Pisum sativum L.). Increases in vacuolar volume could potentially
      protect the cytoplasm by decreasing the cytoplasmic volume during the initial
      phases of salt stress.

PMID- 12520331
TI  - A germination-specific epoxide hydrolase from Euphorbia lagascae.
AB  - The endosperm of Euphorbia lagascae Spreng. seeds contains high levels of the
      epoxidated fatty acid vernolic acid [12(S),13(R)-epoxy-12-octadecenoic acid]. To
      learn more about the function and metabolism of vernolic acid, we have initiated
      an investigation into the gene activities involved in the processes of vernolic
      acid mobilization and oxidation during germination. Here we report the cloning
      and characterization of a soluble epoxide hydrolase from E. lagascae. Epoxide
      hydrolases are a group of functionally related enzymes that catalyze the co
      factor-independent hydrolysis of epoxides to their corresponding vicinal diols by
      the addition of a water molecule. A detailed investigation of the transcription
      pattern of the E. lagascae epoxide hydrolase gene shows that it is induced during
      germination. Results from in situ hybridization show that the gene is expressed
      in the cotyledons and in the hypocotyl. We conclude that soluble epoxide
      hydrolase plays an important role during germination of E. lagascae seeds.

PMID- 12520332
TI  - Cytokinins: new apoptotic inducers in plants.
AB  - High concentrations of cytokinins block cell proliferation and induce programmed
      cell death (PCD) in both carrot ( Daucus carota L.) and Arabidopsis thaliana (L.)
      Heynh. cell cultures [13 and 27 micro M N(6)-benzylaminopurine (BAP),
      respectively]. In the present work, cell death was scored by Evan's blue staining
      and was also demonstrated to be programmed by various parameters, including
      chromatin condensation, oligonucleosomal DNA degradation (laddering), and release
      of cytochrome c from mitochondria. In carrot cells, this induction takes
      approximately 24 h, with proliferating cells being more sensitive than quiescent
      ones. Two hormones, namely abscisic acid and 2,4-dichlorophenoxyacetic acid (2,4
      D), protect cells against the cytokinin-induced death. PCD is not merely a
      consequence of the inability of the culture to proliferate, since high levels of
      2,4-D block carrot cell proliferation without promoting PCD. Increased ethylene
      production was also observed in BAP-treated cultures, although this increase was
      not responsible for PCD because inhibitors of ethylene synthesis and action did
      not block PCD in BAP-treated cultures. Programmed cell death in the form of DNA
      laddering was also seen in plants treated with cytokinins. This process was
      accompanied by accelerated senescence in the form of leaf yellowing.

PMID- 12520333
TI  - Hormone levels and response during de-etiolation in pea.
AB  - The objective of this study was to increase our understanding of the hormonal
      regulation of de-etiolation by investigating endogenous hormone levels and
      response in etiolated pea ( Pisum sativum L.) seedlings after exposure to
      continuous white light. Recent reports suggest that de-etiolation may result from
      the down-regulation of an enzyme in the brassinosteroid (BR) biosynthesis pathway
      in pea. A subsequent review highlighted the need for direct measurements of BR
      levels to support this hypothesis. We have shown that endogenous castasterone and
      6-deoxocastasterone levels are not greatly reduced after exposure to light;
      indeed, 6-deoxocastasterone levels were actually increased. Similarly, the
      elongation response to exogenous brassinolide was greater in plants grown in
      continuous light, or in dark-grown plants that had been transferred into the
      light, than in plants that were grown in continuous darkness. These results
      provide further evidence to suggest that BRs do not negatively regulate de
      etiolation in pea. However, changes in the levels of several other hormones have
      also been implicated in light-regulated development. We have simultaneously
      quantified indole-3-acetic acid (IAA), gibberellin (GA), and abscisic acid levels
      in whole seedlings, which revealed a complex pattern of changes in the levels of
      these substances after exposure to light. The first and most dramatic of these
      changes was a significant reduction in GA(1) levels, which reached a minimum 8 h
      after exposure to light. Whilst GA(1) levels rapidly decreased, IAA levels
      remained unchanged in the short term after exposure to light, suggesting that
      GA(1) levels may be the primary factor regulating the reduction in elongation
      growth during de-etiolation. In the long term after exposure to light, IAA levels
      underwent a transitory increase, which peaked at 48 h, and had abated by 96 h.
      However, abscisic acid levels remained unchanged in the first 1 h after exposure
      to light before undergoing a steady decline over time. The relative importance of
      these changes in mediating light-induced changes in plant morphology is
      discussed.

PMID- 12520334
TI  - Formation of benzoquinol moiety in cornoside by salidroside mono-oxygenase, a
      cytochrome P450 enzyme, from Abeliophyllum distichumcell suspension cultures.
AB  - A microsomal fraction prepared from Abeliophyllum distichumNakai (Oleaceae) cell
      suspension cultures oxidized salidroside, a glucoside of 4-hydroxyphenylethyl
      alcohol, to cornoside possessing a unique benzoquinol ring. The enzyme named
      salidroside mono-oxygenase required NADPH as the only cofactor, and molecular
      oxygen. The reaction was strongly inhibited by CO as well as several cytochrome
      P450 inhibitors, such as cytochrome c and miconazole, indicating the involvement
      of a cytochrome P450 enzyme. Salidroside mono-oxygenase accepted salidroside as
      the only substrate, but did not oxidize 4-hydroxyphenylethyl alcohol, the
      salidroside aglucone, and 4-hydroxybenzoic acid. The optimum pH of the reaction
      was 7.5, and apparent K(m) values for salidroside and NADPH were 44 micro M and
      33 micro M, respectively. The benzoquinol ring formation mechanism is discussed
      in comparison to the mechanism for ipso substitution of 4-hydroxybenzoate by
      active oxygen species followed by elimination leading to hydroquinone.

PMID- 12520335
TI  - A host-specific bacteria-to-plant signal molecule (Nod factor) enhances
      germination and early growth of diverse crop plants.
AB  - Lipo-chitooligosaccharides (LCOs), or Nod factors, are host-specific bacteria-to
      plant signal molecules essential for the establishment of a successful N(2)
      fixing legume-rhizobia symbiosis. At submicromolar concentrations Nod factors
      induce physiological changes in host and non-host plants. Here we show that the
      Nod factor Nod Bj V(C18:1,MeFuc) of Bradyrhizobium japonicum 532C enhances
      germination of a variety of economically important plants belonging to diverse
      botanical families: Zea mays, Oryza sativa (Poaceae), Beta vulgaris
      (Chenopodaceae), Glycine max, Phaseolus vulgaris (Fabaceae), and Gossypium
      hirsutum (Malvaceae), under laboratory, greenhouse and field conditions. Similar
      increases in germination were observed for filtrates of genistein-induced
      cultures of B. japonicum 532C, while non-induced B. japonicum, induced Bj 168 (a
      nodC mutant of B. japonicum deficient in Nod factor synthesis) or the pentamer of
      chitin did not invoke such responses, demonstrating the role of Nod factor in the
      observed effects. In addition, three out of four synthetic LCOs evaluated also
      promoted germination of corn, soybean and Arabidopsis thaliana seeds. LCO also
      enhanced the early growth of corn seedlings under greenhouse conditions. These
      findings suggest the possible use of LCOs for improved crop production.

PMID- 12520336
TI  - Transcriptional regulation of genes encoding subunits of photosystem I during
      acclimation to high-light conditions in Synechocystis sp. PCC 6803.
AB  - Cyanobacteria, algae and plants reduce photosystem contents and modulate
      photosystem stoichiometry upon acclimation to high-light (HL) conditions to avoid
      the damage due to excess light energy. In order to elucidate the molecular
      mechanism of HL acclimation, mRNA levels of genes encoding subunits of
      photosystems were examined in response to change of photon flux density in the
      wild-type strain of Synechocystis sp. PCC 6803. Transcript levels and promoter
      activities of photosystem I (PSI) genes rapidly decreased upon the shift to HL to
      less than 10% of the initial level within 1 h, whereas responses of photosystem
      II (PSII) transcript levels were not coordinated. The prompt change in promoter
      activities of PSI genes, but not PSII genes, seems important for Synechocystis
      cells to regulate their photosystem contents in response to changes in photon
      flux density. The mRNA stabilities of PSI genes also decreased during HL
      incubation. The down-regulation of PSI transcripts under HL did not depend on de
      novo protein synthesis, contrasting with the requirement of newly synthesized
      protein factor(s) for the accumulation of PSI transcripts under low light. When
      gene expression profiles of wild-type cells and a pmgA-disrupted mutant that
      cannot modulate photosystem stoichiometry under HL were compared, a large
      increase in the psaAB and psaA transcript levels was observed in the mutant under
      prolonged exposure to HL for 6 h. Repression of the promoter activity of the psaA
      gene by a pmgA-dependent mechanism was shown to be essential for the adjustment
      of photosystem stoichiometry under HL conditions.

PMID- 12520337
TI  - Thioredoxin and germinating barley: targets and protein redox changes.
AB  - The endosperm and embryo of barley ( Hordeum vulgare L.) grain were investigated
      to relate thioredoxin h and disulfide changes to germination and seedling
      development. The disulfide proteins of both tissues were found to undergo
      reduction following imbibition. Reduction reached a peak 1 day earlier in the
      embryo than in the endosperm, day 1 vs. day 2. The profile in both cases
      resembled those observed with wheat and rice, i.e., the reduction of the storage
      proteins increased initially and then declined during the period of seedling
      growth. The extent of the increase in reduction observed with barley endosperm
      was, however, less pronounced than with the other cereals. Also, unlike wheat and
      rice, the storage proteins of the endosperm were highly reduced in the dry seed
      and the sulfhydryl content of glutelins showed no appreciable change during this
      period. The relative abundance of thioredoxin h during germination and early
      seedling growth differed in the embryo and endosperm: a progressive decrease in
      the endosperm (as seen with wheat) vs. an increase in the embryo. Thioredoxin h
      was found in the major seed tissues in characteristic forms. Three forms were
      found in the scutellum and aleurone, whereas two, which may represent isoforms,
      were identified in the root and the shoot. Using a recently developed strategy
      based on two-dimensional gel electrophoresis, several proteins were identified as
      specific targets for thioredoxin in the embryo following oxidation with H(2)O(2),
      among them barley embryo globulin 1, peroxiredoxin and acidic ribosomal protein
      P(3). The results confirm earlier findings with the endosperm of other cereals
      and extend the importance of thioredoxin-linked redox change to the germinating
      embryo for functions that potentially include dormancy, protection against
      reactive oxygen species, translation and the mobilization of storage proteins.

PMID- 12520338
TI  - Opposing effects of reduced DNA methylation on flowering time in Arabidopsis
      thaliana.
AB  - Demethylation of DNA promotes flowering in plants from the vernalization
      responsive ecotype C24 of Arabidopsis thaliana (L.) Heynh., but delays flowering
      in the ecotype Landsberg erecta which is not responsive to vernalization. To
      investigate these contrasting effects of low methylation we have monitored
      flowering times and expression of two repressors of flowering, FLC and FWA, in
      low-methylation plants from three late-flowering mutants in the ecotype Landsberg
      erecta. Demethylation of DNA decreased FLC expression in the vernalization
      responsive mutants, but was not associated with a promotion of flowering; rather,
      in some lines, demethylation delayed flowering. The opposing effects of
      demethylation could be explained by its differential effect on the expression of
      two repressors of flowering. FLC was down-regulated in plants with low
      methylation, promoting flowering, while FWA was activated in response to
      demethylation, which probably delays the transition to flowering. Expression of
      the FWA gene did not delay flowering in plants of ecotype C24; our data suggest
      that the FWA protein of C24 may be non-functional.

PMID- 12520339
TI  - Overexpression of a soybean cytosolic glutamine synthetase gene linked to organ
      specific promoters in pea plants grown in different concentrations of nitrate.
AB  - A glutamine synthetase gene ( GS15) coding for soybean cytosolic glutamine
      synthetase (GS1) fused to a constitutive promoter (CaMV 35S), a putative nodule
      specific promoter (LBC(3)) and a putative root-specific promoter (rolD) was
      transformed into Pisum sativum L. cv. Greenfeast. Four lines with single copies
      of GS15 (one 35S-GS15 line, one LBC (3) -GS15 line, and two rolD-GS15 lines) were
      tested for the expression of GS15, levels of GS1, GS activity, N accumulation,
      N(2) fixation, and plant growth at different levels of nitrate. Enhanced levels
      of GS1 were detected in leaves of three transformed lines (the 35S-GS15 and rolD
      GS15 transformants), in nodules of three lines (the LBC (3) -GS15 and rolD-GS15
      transformants), and in roots of all four transformants. Despite increased levels
      of GS1 in leaves and nodules, there were no differences in GS activity in these
      tissues or in whole-plant N content, N(2) fixation, or biomass accumulation among
      all the transgenic lines and the wild-type control. However, the rolD-GS15
      transformants, which displayed the highest levels of GS1 in the roots of all the
      transformants, had significantly higher GS activity in roots than the wild type.
      In one of the rolD-GS15 transformed lines (Line 8), increased root GS activity
      resulted in a lower N content and biomass accumulation, supporting the findings
      of earlier studies with Lotus japonicus (Limami et al. 1999 ). However, N content
      and biomass accumulation was not negatively affected in the other rolD-GS15
      transformant (Line 9) and, in fact, these parameters were positively affected in
      the 0.1 mM treatment. These findings indicate that overexpression of GS15 in
      various tissues of pea does not consistently result in increases in GS activity.
      The current study also indicates that the increase in root GS activity is not
      always consistent with decreases in plant N and biomass accumulation and that
      further investigation of the relationship between root GS activity and growth
      responses is warranted.

PMID- 12520340
TI  - Characterization of two phases of chlorophyll formation during greening of
      etiolated barley leaves.
AB  - The esterification kinetics of chlorophyllide, obtained by a single flash of
      light, were investigated in etiolated barley ( Hordeum vulgare L.) and oat (
      Avena sativa L.) leaves. A rapid phase, leading to esterification of 15% of total
      chlorophyllide within 15-30 s, was followed by a lag-phase of nearly 2 min and a
      subsequent main phase, leading to esterification of 85% of total chlorophyllide
      within 30-60 min. The presence of additional protochlorophyllide, produced in the
      leaves by incubation with 5-aminolevulinate, did not change the esterification
      kinetics. The rapid phase was identical after partial (11-15%) and full (>80%)
      photoconversion of protochlorophyllide; the ability for a second rapid
      esterification phase was restored in a dark period of at least 10 min. Cooling
      the leaves to 0 degrees C abolished the esterification of the main phase while
      the rapid phase remained unchanged. The prolamellar bodies were already in part
      transformed into prothylakoid-like structures within 2-5 min after a full flash
      but not after a weak flash (11% photoconversion); in the latter case, the
      corresponding transformation required a dark period of about 45 min. The
      existence of subcomplexes of prolamellar bodies containing
      NADPH:protochlorophyllide oxidoreductase and chlorophyll synthase in the ratio
      7:1 is discussed.

PMID- 12520341
TI  - Gentiobiose: a novel oligosaccharin in ripening tomato fruit.
AB  - Two neutral disaccharides, gentiobiose [beta- D-Glc p-(1-->6)- D-Glc] and
      nigerose [alpha- D-Glc p-(1-->3)- D-Glc], were detected in tomato ( Lycopersicon
      esculentum Mill.) pericarp and locule. Gentiobiose was present in the locule of
      green fruit and ripe fruit at 0.88 and 5.8 micro mol (kg fresh weight)(-1),
      respectively. When vacuum-infiltrated into green tomato fruit, exogenous
      gentiobiose (50 or 200 micro g per fruit) hastened the initiation of ripening (as
      judged by colour change) by 1-3 days relative to fruit that were infiltrated with
      glucose or isomaltose. Nigerose plus gentiobiose was particularly effective, but
      nigerose alone had no significant effect. The endogenous disaccharides were found
      to be present in the apoplastic fluid of the fruit, compatible with a proposed
      intercellular signalling role. The origin and metabolic fate of the disaccharides
      were investigated. Phenolic esters of these disaccharides were not detectable in
      tomato fruit and it is therefore unlikely that the free disaccharides were formed
      from a pool of such esters. An alternative possible biosynthetic origin, via
      transglycosylation, is discussed. When [(14)C]gentiobiose was vacuum-infiltrated
      into unripe or ripe fruit, the disaccharide remained intact for at least 1 h but
      was largely degraded within 24 h. The results suggest that gentiobiose is a new,
      naturally occurring oligosaccharin with a rapid turnover rate.

PMID- 12520342
TI  - Multiform biosynthetic pathway of syringyl lignin in angiosperms.
AB  - To clarify the pathway for biosynthesis of sinapyl alcohol in angiosperms, tracer
      experiments using stable isotopes were performed on robinia ( Robinia
      pseudoacacia L.), oleander ( Nerium indicum Mill.), magnolia ( Magnolia kobus
      DC.) and Arabidopsis thaliana (L.) Heynh. Precursors used in the experiment were
      (13)C- and (2)H ( D)-labeled [8-(13)C, 3-OCD(3)]ferulic acid and [8-(13)C, 3,5
      OCD(3)]sinapic acid. The incorporation of labeled precursor into lignin was
      confirmed by gas chromatography-mass spectrometry of the products of
      derivatization followed by reductive cleavage. Crude extracts of differentiating
      xylem or stems from these plants were also assayed for 4-coumarate-CoA ligase
      (4CL; EC 6.2.1.12) activity using sinapic acid and ferulic acid as substrates. In
      robinia and oleander, 4CL activity toward sinapic acid was detected, and labeled
      sinapic acids were incorporated into syringyl lignin. These results indicate that
      robinia and oleander have a pathway that produces sinapyl alcohol from sinapic
      acid via sinapoyl-CoA. By contrast, in magnolia and Arabidopsis, 4CL activity
      toward sinapic acid could not be detected, and labeled sinapic acid was not
      incorporated into lignin. These results suggest that syringyl lignin biosynthesis
      in angiosperms operates via multiple pathways that depend on the species.

PMID- 12520343
TI  - In vitro biosynthesis of 1,4-beta-galactan attached to a pectin-xyloglucan
      complex in pea.
AB  - Particulate enzyme preparations were prepared from etiolated pea ( Pisum sativum
      L.) epicotyls and used to assay for 1,4-beta-galactan synthase using UDP-[U
      (14)C]galactose. Optimum conditions for 1,4-beta-galactan synthesis were
      determined. The enzyme products were characterized by selective enzymic
      degradation, gel permeation chromatography and anion-exchange chromatography.
      Evidence was obtained for the formation of 1,4-beta-galactan chain attached to a
      pectic backbone containing both polygalacturonic acid and rhamnogalacturonan I.
      The results also indicated that part or all of this nascent pectin was present as
      a complex with xyloglucan.

PMID- 12520344
TI  - Development of Agrobacterium tumefaciens C58-induced plant tumors and impact on
      host shoots are controlled by a cascade of jasmonic acid, auxin, cytokinin,
      ethylene and abscisic acid.
AB  - The development of Agrobacterium tumefaciens-induced plant tumors primarily
      depends on the excessive production of auxin and cytokinin by enzymes encoded on
      T-DNA genes integrated into the plant genome. The aim of the present study was to
      investigate the involvement of additional phytohormone signals in the
      vascularization required for rapid tumor proliferation. In stem tumors of Ricinus
      communis L., free auxin and zeatin riboside concentrations increased within 2
      weeks to 15-fold the concentrations in control stem tissue. Auxin and cytokinin
      immunolocalization revealed the highest concentrations within and around tumor
      vascular bundles with concentration gradients. The time-course of changes in free
      auxin concentration in roots was inversely correlated with that in the tumors.
      The high ethylene emission induced by increased auxin- and cytokinin correlated
      with a 36-fold accumulation of abscisic acid in tumors. Ethylene emitted from
      tumors and exogenously applied ethylene caused an increase in abscisic acid
      concentrations also in the host leaves, with a diminution in leaf water vapor
      conductance. Jasmonic acid concentration reached a maximum already within the
      first week of bacterial infection. A wound effect could be excluded. The results
      demonstrate the concerted interaction of a cascade of transiently induced, non-T
      DNA-encoded phytohormones jasmonic acid, ethylene and abscisic acid with T-DNA
      encoded auxin and zeatin riboside plus trans-zeatin, all of which are required
      for successful plant tumor vascularization and development together with
      inhibition of host plant growth.

PMID- 12520345
TI  - Structural and functional characterization of the phytoene synthase promoter from
      Arabidopsis thaliana.
AB  - The expression of the gene coding for the carotenogenic enzyme phytoene synthase
      is highly regulated. To study this, its promoter and truncated versions thereof
      were translationally fused to the luciferase gene as a reporter and these
      constructs were used to transform Arabidopsis thaliana. The full-length promoter
      was shown to be active in the dark, but mediated positive responses towards
      different light qualities (far-red, red, blue and white light). Among the
      herbicides tested, norflurazon and gabaculine showed no notable effects, while
      CPTA abolished light induction completely. Response towards different light
      qualities was mediated by a TATA box-proximal promoter region up to position 
      300, containing G-box-like elements involved in the distinction of different
      monochromatic light qualities applied. This is detected in electrophoretic
      mobility shift assays (EMSAs), which reveal differential complex formation. A
      TATA box distal region of the promoter was shown to be responsible for a high
      basal promoter activity that was not modulated by different light qualities.
      Using EMSAs, a novel cis-acting element ATCTA occurring in tandem between
      positions -854 and -841 proved to be decisive in this respect. The motif was
      found in several other promoter regions involved in carotenoid and tocopherol
      biosynthesis, as well as in the promoter regions mediating the expression of
      photosynthesis-related genes. The functional equivalence of the motifs was shown
      by successfully using the respective regions in EMSAs. We conclude that the ATCTA
      motif represents an element capable of mediating a coordinated regulation of
      these pathways at the transcriptional level.

PMID- 12520346
TI  - Integration of photo- and chemosensory signaling pathways in Chlamydomonas.
AB  - The behavior of Chlamydomonas reinhardtii Dangeard is regulated by both light and
      chemical stimuli. Generation of a transmembrane photoreceptor current is the
      earliest so far resolved event in phototaxis of green flagellates. Tryptone
      rapidly inhibits the photoreceptor current in gametes of C. reinhardtii and
      induces their accumulation. The time-course, concentration dependence and
      induction during gametogenesis of these two processes coincide. On the other
      hand, tryptone causes a weak stimulation of the photoreceptor current in the
      absence of any behavioral responses in vegetative cells. This shows that the
      tryptone-induced inhibition of the photoreceptor current in C. reinhardtii is due
      to activation of a gamete-specific chemosensory system, and that integration of
      the photo- and chemosensory signals already occurs at the initial steps of the
      signaling pathways.

PMID- 12520347
TI  - Phonosurgery of the vocal folds: a classification proposal.
AB  - The Phonosurgery Committee of the European Laryngological Society (ELS) has
      examined the definition and technical description of phonosurgical procedures.
      Based on this review, the committee has proposed a working classification. The
      current presentation is restricted to vocal fold surgery (VFS) with phonosurgical
      intent. Both the pathology and the therapeutic aim define VFS: (1). vocal fold
      lesions that impair vibratory movements require excision (e.g., vocal fold
      nodule), incision and suction (e.g., Reinke's edema), dissection and/or
      augmentation (e.g., sulcus-vergeture), coagulation or vaporization (e.g.,
      varicosity) and incision and stenting (e.g., glottal web); (2.vocal fold movement
      disorders require position and/or tension correction by augmentation (e.g., vocal
      fold paresis), injection (e.g., botulinum toxin for spasmodic dysphonia) and
      excision (e.g., dysphonia plicae ventricularis). This presentation excludes
      surgical instrumentation, implants or injectable materials. Being essentially
      surgeon-dependent, usage may vary over time and with experience.

PMID- 12520348
TI  - Secondary placement of a voice prosthesis after total pharyngolaryngectomy with
      colon interposition: voice restoration in colon interposition.
AB  - We present a patient treated by a total pharyngolaryngoesophagectomy and
      postoperative radiotherapy for a hypopharyngeal T4N2bM0 squamous cell carcinoma.
      The upper digestive tract was reconstructed with a pedicled left colon
      interposition through the posterior mediastinum. A voice prosthesis was placed 9
      months after the initial treatment, following measurement of the tracheo
      neopharyngeal wall thickness by sonography. Fifteen months after the total
      pharyngolaryngectomy, the patient remains free of recurrent disease and has
      successfully resumed speaking with the voice prosthesis.

PMID- 12520349
TI  - Perilymphatic and endolymphatic pressures during endolymphatic hydrops.
AB  - We analysed the fluid pressure in the perilymphatic and endolymphatic spaces of
      the cochlea in eight guinea pigs after endolymphatic hydrops (EH) was surgically
      created. The control experiments were done in the opposite ears. EH was
      histologically confirmed after the conclusion of the pressure measurements. No
      statistically significant pressure difference between the scala media and the
      scala tympani was found, either in ears with EH or the control ears. However, the
      endocochlear potential, which we evaluated for position verification of the
      measurement pipette in the cochlea, was statistically significantly decreased in
      ears with EH.

PMID- 12520350
TI  - Management strategies in neurofibromatosis type 2.
AB  - The objective of this study was to review the experience of the Neurotology and
      Skull Base Surgery Unit of Addenbrooke's Hospital in Cambridge, England, in the
      management of patients with neurofibromatosis type 2 (NF2). This was a
      retrospective review of the institution's series conducted at a neurotological
      tertiary referral centre. Over a 17-year period (1984-2001), 35 patients with NF2
      were managed. These patients presented with multiple cranio-spinal neoplasms,
      including 62 cerebellopontine angle tumours of which 59 were vestibular
      schwannomas (nine patients with unilateral tumours and 25 patients with bilateral
      tumours). Clinical presentation, diagnosis and patient management were reviewed.
      The outcome parameters measured were tumour progression, the incidence of
      complications (hearing deterioration and facial nerve palsy) and the need for
      secondary intervention. Five vestibular schwannomas were treated with
      stereotactic radiosurgery (gamma-knife), all of which showed evidence of
      progression in size and/or deterioration in hearing. Thirty-one VS were
      conservatively treated with annual surveillance. In nine cases, the tumours had a
      follow-up shorter than 6 months and were therefore excluded from the results. In
      13 cases the VS did not progress in size, and the hearing remained stable, while
      in the remaining nine cases, tumour progression was evident. In fifteen cases,
      surgery was performed at the authors' institution. In 11 cases a
      translabyrinthine approach was adopted, and in the remaining four cases a
      retrosigmoid approach was preferred. In all these cases, tumour removal was total
      and facial nerve function was House-Brackmann grade I-III in 55%. Successful
      hearing preservation was elusive in those patients in whom a hearing preservation
      approach was attempted. NF2 remains an extremely challenging disorder for the
      neurotologist and the patient alike. Early diagnosis offers distinct advantages
      to the patients, their families and the community at large. Of the treatment
      modalities, surgery unequivocally offers the most superior tumour control.
      Hearing preservation remains a challenge in these patients, but is optimised by
      the early detection of tumours in the NF2 patient.

PMID- 12520351
TI  - The effect on the middle-ear cavity of an absorbable gelatine sponge alone and
      with corticosteroids.
AB  - The objectives of this study were to establish whether there is an obvious
      difference between intact mucosa and abraded mucosa of the middle-ear cavity in
      respect to the potential side effects from the application of absorbable gelatine
      sponge (Gelfoam) and to investigate if Gelfoam combined with corticosteroid
      ointment (cortimycine, sterile 1% hydrocortisone acetate) can reduce the
      occurrence of these effects. Twenty Albino rats were used in the study. These
      animals were divided into four groups, with ten ears in each group. In group A,
      the middle-ear mucosa was kept intact, and Gelfoam was inserted into the middle
      ear cavity. In group B, the middle-ear mucosa was abraded, and Gelfoam was
      inserted. In group C, Gelfoam with corticosteroid was implanted over the intact
      mucosa, and in group D, the mucosa was abraded prior to the insertion of Gelfoam
      with corticosteroid. The changes were evaluated 8 weeks postoperatively. In group
      A, there was a minimal increase in fibroblastic activity, vascular proliferation
      with mild to moderate fibrosis and all but two tympanic membranes were perfectly
      normal. However, in group B, we encountered a significant increase in
      fibroblastic activity, vascular proliferation and fibrosis, and we observed that
      all tympanic membranes were moderately to severely thickened. These
      histopathologic changes related to Gelfoam were noted to be decreased in group C
      and especially in group D. As previously reported in the literature, Gelfoam was
      found to promote the formation of connective tissue in the middle-ear cavity
      regardless of the status of the mucosa. The unwanted effects of this material may
      be decreased if it is combined with corticosteroids in the middle-ear cavity.

PMID- 12520352
TI  - Concomitant otomycosis and dermatomycoses: a clinical and microbiological study.
AB  - Otomycosis tends to recur despite long-term treatment. To our knowledge, there is
      no study in the English literature concerning the clinical importance of
      concomitant otomycosis and dermatomycoses. We investigated the presence of
      dermatomycoses in 52 patients with otomycosis in order to document the clinical
      and microbiological importance of their coexistence. Dermatomycoses on the feet
      and/or hands were identified in 19 patients (36.5%). The most common pathogen for
      otomycosis was Aspergillus niger, while it was Candida albicans for the
      dermatomycoses. The same pathogenic fungi were isolated from the otomycosis and
      dermatomycoses in nine of the 19 patients (47.4%). Aspergillus niger was the most
      common shared pathogen. The pathogens isolated in concomitant dermatomycoses were
      common pathogens for the fungal infection of the ear ( Aspergillus niger,
      Aspergillus flavus, Aspergillus fumigatus, Candida albicans). It was concluded
      that the autoinoculation of the ear canal by pathogenic fungi might be possible
      in the presence of the untreated dermatomycoses. Dermatomycoses must be
      investigated in patients with otomycosis and must be treated simultaneously in
      order to prevent the recurrence of both.

PMID- 12520354
TI  - Evaluation of factors concerning the patency of the internal jugular vein after
      functional neck dissection.
AB  - The aim of this study was to evaluate the effects of several factors on the
      patency of the internal jugular vein (IJV) after functional neck dissection
      (FND). A prospective clinical study was undertaken in 21 patients (36 neck
      dissections) before and after FND at the 1st and 3rd postoperative months by
      using duplex Doppler ultrasonography. The patients who had radiation therapy (RT)
      were evaluated again in the 6th postoperative month in order to assess possible
      late effects of radiation therapy. In our patients the patency rate was 100%, and
      no thrombosis was found. But the area at rest and during Valsalva's maneuver was
      reduced, and this difference was found to be statistically significant. It was
      concluded that the patency of the IJV remains normal after FND. Radiation
      therapy, infection or fistula formation have no detrimental effects on patency.
      In addition, the number of ligated branches do not seem to be related to the
      patency rate.

PMID- 12520353
TI  - Prognostic value of cell proliferation markers, tumour suppressor proteins and
      cell adhesion molecules in primary squamous cell carcinoma of the larynx and
      hypopharynx.
AB  - In an attempt to identify molecular prognostic markers, a series of laryngeal and
      hypopharyngeal carcinomas was examined for PCNA, Ki67, p27(Kip1), p53, E-cadherin
      and CD44 by immunohistochemistry and for DNA content by flow cytometry. No
      correlation was found between E-cadherin, CD44, p53 or DNA ploidy and the
      clinicopathological data. The fraction of cancer cells immunolabelled for
      p27(Kip1) correlated with tumour differentiation, but not with lymph node
      metastasis. In contrast, the PCNA, Ki67 and S-phase fractions of cancer cells
      were significantly higher in tumours with lymph node metastasis than in those
      without lymph node metastasis and were correlated with pathological T-stages and
      with tumour dedifferentiation. In univariate analysis, advanced pathological T
      stage, lymph node metastasis and high fractions of cancer cells immunolabelled
      for PCNA or Ki67 inversely correlated with overall and disease-free survival. In
      multivariate analysis, lymph node metastasis was the only factor significantly
      associated with poor survival. The data suggest that immunohistochemical
      investigation of PCNA and Ki67 and flow cytometric analysis of S-phase fractions
      may be useful predictive markers of biological aggressiveness in laryngeal
      carcinomas.

PMID- 12520355
TI  - Spontaneous internal jugular vein thrombosis associated with distant
      malignancies.
AB  - Internal jugular vein (IJV) thrombosis is an extremely rare vascular disease that
      is easily overlooked or misdiagnosed. It is usually secondary to intravenous drug
      abuse, prolonged central venous catheterization or deep head-neck infections or
      trauma. Associated malignancies, either known or occult, are also uncommon and
      not well documented in the etiology of IJV thrombosis. A previously healthy, 48
      year-old man presented to our Ear, Nose and Throat (ENT) Department with pain and
      swelling of the right side of the neck, which had been going on for a period of 9
      days, with the absence of any other ENT symptoms. Examination of his neck showed
      swelling and tenderness along the anterior border of the right
      sternocleidomastoid muscle. An ultrasound scan of the neck confirmed right IJV
      thrombosis. Further investigation to determine the cause for the thrombosis
      revealed two coincidental malignancies: prostate and lung. This shows that every
      patient with spontaneous thrombophlebitis must undergo a careful history, a
      complete physical examination and a thorough investigation to avoid missing or
      delaying the diagnosis of a hidden malignancy.

PMID- 12520356
TI  - Studies on the radioprotective potency of amifostine on salivary glands of rats
      during fractionated irradiation: acute and late effects.
AB  - The purpose of this study was to evaluate the radioprotective potential of
      amifostine on the salivary glands of rats with respect to the acute and late
      effects. The head and neck area of WAG/RijH rats was irradiated with (60)Co-gamma
      rays (60 Gy/30f for 6 weeks). Amifostine (250 mg/m(2) body surface) or an equal
      volume of physiologic saline was applied intravenously 15 min before each
      irradiation. In the course of treatment the salivary glands were examined
      histopathologically. Body weight was measured sequentially during irradiation. A
      cytoprotective effect of amifostine on the acute toxicity of salivary glands
      could not be detected under fractionated irradiation. However, late effects such
      as fibrosis and necrosis of the glands 6 months after irradiation were less
      developed in the amifostine group. The weight loss of the amifostine-treated
      animals during fractioned irradiation was higher than in the irradiated group.
      Amifostine has a significant cytoprotective effect on the late toxicity of
      irradiated salivary glands. However, the acute toxicity of the glands during
      radiotherapy cannot be reduced.

PMID- 12520357
TI  - Bilateral submandibular duct relocation for drooling: an evaluation of results
      for the Birmingham Children's Hospital.
AB  - Drooling is a problem of the neurologically impaired that often leads to
      stigmatisation and social isolation. Bilateral submandibular duct relocation
      (BSMDR) is a surgical procedure that may be used to control troublesome drooling.
      The aim of this study was to assess the results following surgery and attempt to
      identify those factors that would mitigate against a successful outcome. A
      retrospective case note review was performed, and data were collected on 23
      neurologically impaired patients who underwent the procedure between 1993 and
      2000 at the Birmingham Children's Hospital, UK. An overall improvement in
      drooling was demonstrated in 20 (87%) cases, with complete cessation of drooling
      in 13 (57%) cases. The complications included one ranula, three transient
      submandibular gland swellings and two persistent swellings requiring gland
      excision. It is difficult to predict which patients will have an unsuccessful
      outcome following surgery. In our series, three (13%) patients had poor results.
      We could not determine any special features that could account for this, except
      that these patients in particular demonstrated the greatest degree of oral-motor
      dysfunction. BSMDR is a technically straightforward procedure associated with
      minimal morbidity and a high success rate. It is the procedure of choice at our
      institution.

PMID- 12520358
TI  - Otolaryngologic aspects of tetanus.
AB  - Tetanus is considered a major health problem in the developing and under
      developed countries, with approximately 1 million new cases occurring each year.
      We have evaluated the tetanus patients and their presenting complaints, the
      clinical findings and their relations to the head and neck region along with the
      frequency of otolaryngological findings and their correlation to the prognosis of
      this highly mortal disease. There were a total of 37 patients with generalized
      tetanus diagnosed and treated between 1991 and 2001. There were 25 women and 12
      men with a mean age of 55+/-15.6 years. The most common presenting symptom was
      trismus, followed by neck pain, dysphagia, generalized pain and facial muscular
      contractions. Wound evaluation revealed that 72.9% of the patients had tetanus
      prone wounds, and 27% had either no obvious wounds or a wound considered to be
      trivial by the patient. Only 62% percent of the patients had sought medical
      attention immediately after being injured. Three patients in our series were
      admitted to the otolaryngology clinic with upper aerodigestive tract symptoms. A
      comparison of complaints with clinical findings revealed a significant lack of
      correlation, emphasizing that complete physical examination must be performed
      when evaluating patients with trismus, dysphagia and neck pain. Tracheotomy was
      performed in 21 cases. There was a direct correlation between the clinical stage
      and the requirement of tracheotomy. Wound debridment was performed, and
      antibiotherapy, tetanus toxoid vaccine and immunoglobulin were administered. The
      mortality rate was 59.4% (22/37). Shorter incubation periods and periods of onset
      and a higher grade of disease were significantly related to high mortality rates
      ( P=0.001). It is important to realize the fact that instead of looking for
      tetanus-prone wounds, one should be on the lookout for tetanus-prone patients.
      Consequently, on the part of the otolaryngologist, there should always be a high
      index of suspicion, and concerning patients with trismus or subacute progressive
      dysphagia, the possibility of tetanus must be borne in mind.

PMID- 12520359
TI  - Algal and cyanobacterial biofilms on calcareous historic buildings.
AB  - Major microorganisms in biofilms on external surfaces of historic buildings are
      algae, cyanobacteria, bacteria, and fungi. Their growth causes discoloration and
      degradation. We compared the phototrophs on cement-based renderings and limestone
      substrates at 14 historic locations (47 sites sampled) in Europe and Latin
      America. Most biofilms contained both cyanobacteria and algae. Single-celled and
      colonial cyanobacteria frequently constituted the major phototroph biomass on
      limestone monuments (32 sites sampled). Greater numbers of phototrophs, and
      especially of algae and of filamentous morphotypes, were found on cement-based
      renderings (15 sites), probably owing to the porosity and small pore size of the
      latter substrates, allowing greater entry and retention of water. All
      phototrophic groups were more frequent on Latin American than on European
      buildings (20 and 27 sites, respectively), with cyanobacteria and filamentous
      phototrophs showing the greatest differences. The results confirm the influence
      of both climate and substrate on phototroph colonization of historic buildings.

PMID- 12520360
TI  - Cloning and characterization of katA, encoding the major monofunctional catalase
      from Xanthomonas campestris pv. phaseoli and characterization of the encoded
      catalase KatA.
AB  - The first cloning and characterization of the gene katA, encoding the major
      catalase (KatA), from Xanthomonas is reported. A reverse genetic approach using a
      synthesized katA-specific DNA probe to screen a X. campestris pv. phaseoli
      genomic library was employed. A positively hybridizing clone designated pKat29
      that contained a full-length katA was isolated. Analysis of the nucleotide
      sequence revealed an open reading frame of 1,521 bp encoding a 507-amino acid
      protein with a theoretical molecular mass of 56 kDa. The deduced amino acid
      sequence of KatA revealed 84% and 78% identity to CatF of Pseudomonas syringae
      and KatB of P. aeruginosa, respectively. Phylogenetic analysis places Xanthomonas
      katA in the clade I group of bacterial catalases. Unexpectedly, expression of
      katA in a heterologous Escherichia coli host resulted in a temperature-sensitive
      expression. The KatA enzyme was purified from an overproducing mutant of X.
      campestris and was characterized. It has apparent K(m) and V(max) values of 75 m
      M [H(2)O(2)] and 2.55 x 10(5) micromol H(2)O(2) micromol heme(-1) s(-1),
      respectively. The enzyme is highly sensitive to 3-amino-1,2,4-triazole and
      NaN(3), has a narrower optimal pH range than other catalases, and is more
      sensitive to heat inactivation.

PMID- 12520361
TI  - Complementation of bacteriophage induction and recombination defects in
      Escherichia coli RecA(-) mutants by expression of the cloned T4 bacteriophage
      uvsX gene.
AB  - Previous workers reported that the T4 bacteriophage UvsX protein could promote
      neither RecA-LexA-mediated DNA repair nor induction of lysogenized bacteriophage,
      only recombination. Reexamination of these phenotypes demonstrated that, in
      contrast to these prior studies, when this gene was cloned into a medium but not
      a low-copy-number vector, it stimulated both a high frequency of spontaneous
      induction and mitomycin C-stimulated bacteriophage induction in a strain
      containing a recA13 mutation, but not a recA1 defect. The gene when cloned into a
      low- or medium- copy-number vector also promoted a low frequency of recombination
      of two duplicated genes in Escherichia coli in a strain with a complete recA gene
      deletion. These results suggest that a narrow concentration range of T4 UvsX
      protein is required to promote both high-frequency spontaneous and mitomycin C
      stimulated bacteriophage induction in a recA13 gene mutant, but it facilitates
      recombination of duplicated genes at only a very low frequency in E. coli RecA(-)
      mutants with a complete recA deletion. These results also suggest that the
      different UvsX phenotypes are affected differentially by the concentration of
      UvsX protein present.

PMID- 12520362
TI  - Cloning and characterization of a cytolytic and mosquito larvicidal delta
      endotoxin from Bacillus thuringiensis subsp. darmstadiensis.
AB  - The cytolytic delta-endotoxin gene from Bacillus thuringiensis subsp.
      darmstadiensis was amplified from genomic DNA by PCR by using primers designed
      from the sequence of cyt2Aa1 gene of B. thuringiensis subsp. kyushuensis. DNA
      sequence analysis revealed an open reading frame translating to a 259-amino acid
      sequence. The cloned gene was designated cyt2Aa2. This gene was highly expressed
      in Escherichia coli as inclusion bodies that could be solubilized in 50 m M
      Na(2)CO(3), pH 10.5. Activation of the solubilized protoxin by proteinase K (1%
      wt/wt, proteinase K/protoxin) yielded the active fragment of about 23 kDa.
      Cyt2Aa2 showed high hemolytic activity against sheep erythrocytes (hemolytic end-
      point 0.25 microgram/ml) and was toxic to Culex quinquefasciatus and Aedes
      aegypti larvae (LC(50) 0.5-1.0 microgram/ml).

PMID- 12520363
TI  - Growth optimization procedures for the phytopathogen Xylella fastidiosa.
AB  - For the first time, growth curves are shown for the phytopathogen Xylella
      fastidiosa on traditional growth media such as PW (periwinkle wilt), BCYE
      (buffered charcoal yeast extract), and on new ones such as GYE (glutamate yeast
      extract) and PYE (phosphate yeast extract) that were developed in this work. The
      optimal growth conditions on solid and liquid media as well as their measurements
      are presented, by using total protein content and turbidity determinations. The
      results demonstrated that yeast extract provided sufficient nutrients for X.
      fastidiosa, since the cells grew well on PYE medium.

PMID- 12520364
TI  - Preferential inhibition of protein synthesis by ketolide antibiotics in
      Haemophilus influenzae cells.
AB  - The ketolide antibiotics are semi-synthetic derivatives of erythromycin A with
      enhanced inhibitory activity in a wide variety of microorganisms. They have
      significantly lower MICs than the macrolide antibiotics for many Gram-positive
      organisms. Two ketolides, telithromycin and ABT-773, were tested for growth
      inhibitory effects in Haemophilus influenzae. Both antibiotics increased the
      growth rate and reduced the viable cell number with IC(50) values of 1.5
      microgram/ml. Protein synthesis was inhibited in cells with a similar IC(50)
      concentration (1.25 microgram/ml). Macrolide and ketolide antibiotics have been
      shown to have a second equivalent target for inhibition in cells, which is
      blocking the assembly of the 50S ribosomal subunit. Pulse and chase labeling
      assays were conducted to examine the effect of the ketolides on subunit formation
      in H. influenzae. Surprisingly, both antibiotics inhibited 50S and 30S subunit
      assembly to the same extent, with no specific effect of the compounds on 50S
      assembly. Over a range of antibiotic concentrations, 30S particle synthesis was
      diminished to the same extent as 50S formation. H. influenzae cells seem to have
      only one significant target for these antibiotics, and this may help to explain
      why these drugs are not more effective than the macrolides in preventing the
      growth of this microorganism.

PMID- 12520365
TI  - Porphyromonas gingivalis modulates the production of interleukin 8 and monocyte
      chemotactic protein 1 in human vascular endothelial cells.
AB  - Porphyromonas gingivalis seems to perturb the cytokine network to maintain
      periodontal disease. Although endothelial cells are a leading source of
      interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), the effect of P.
      gingivalis on the cells remains unclear. We used reverse transcription-PCR (RT
      PCR) to assess levels of IL-8 and MCP-1 mRNA and enzyme-linked immunosorbent
      assays (ELISA) to evaluate their protein production by human umbilical vein
      endothelial cells (HUVEC) challenged with P. gingivalis. IL-8 and MCP-1 protein
      levels decreased in response to challenge with P. gingivalis, and N-a- p-tosyl- L
      lysine chloromethylketone (TLCK) prevented the degradation of these chemokines.
      Furthermore, the bacteria upregulated expression of the mRNAs of these
      chemokines. Our results indicate that P. gingivalis proteases degraded IL-8 and
      MCP-1. Degradation of chemokines secreted from endothelial cells may decrease the
      recruitment of leukocytes and their migration through the endothelium, thus
      contributing to a delay in the host immune defense mechanism.

PMID- 12520366
TI  - Organization of carboxysome genes in the thiobacilli.
AB  - The order of genes in the carboxysome gene clusters of four thiobacilli was
      examined and the possibility of the cluster forming an operon evaluated.
      Furthermore, carboxysome peptide homologs were compared with respect to
      similarities in primary sequence, and the unique structural features of the shell
      protein CsoS2 were described.

PMID- 12520367
TI  - Morphological changes of Pseudomonas pseudoalcaligenes in response to temperature
      selection.
AB  - Adaptation to novel environments usually entails morphological changes. The cell
      morphology of six experimental populations of Pseudomonas pseudoalcaligenes and
      their common ancestor were examined with scanning electron microscopy (SEM). The
      six experimental populations were propagated under different temperatures for 10
      months: three of them cultured at constant normal temperature (35 degrees C)
      forming the control group, and the other three cultured at incremental higher
      temperatures (from 41 degrees to 47 degrees C) as the HT group. SEM showed the
      deformed and elongated cells in the 6-h cultures of both ancestral and control
      populations at 45 degrees C, indicating that 45 degrees C is stressful for the
      ancestral and the control populations. In contrast, the HT populations retained
      normal cell shape in the 6-h cultures at both 35 degrees C and 45 degrees C. The
      mean cell volumes of control and HT populations increased 29% and 34%,
      respectively, relative to the ancestor at their respective thermal regimens,
      suggestion that the culturing conditions might favor larger cells.

PMID- 12520368
TI  - Accumulation of a cocoa-butter-like lipid by Yarrowia lipolytica cultivated on
      agro-industrial residues.
AB  - Yarrowia lipolytica was cultivated on mixtures of saturated free fatty acids (an
      industrial derivative of animal fat called stearin), technical glycerol (the main
      by-product of bio-diesel production facilities), and glucose. The utilization of
      technical glycerol and stearin as co-substrates resulted in higher lipid
      synthesis and increased citric acid production than the combination of glucose
      and stearin. The lipids produced contained significant amounts of stearic acid
      (50-70%, wt/wt) and lower ones of palmitic (15-20%, wt/wt), oleic (7-20%, wt/wt),
      and linoleic (2-7%, wt/wt) acid. Single-cell oil having a composition similar to
      cocoa-butter up to 3.4 g/L was produced, whereas in some cases relatively
      increased citric acid quantities (up to 14 g/L) were excreted into the growth
      medium. The microorganism presented a high specificity for lauric, myristic, and
      palmitic acid, while a discrimination for the stearic acid was observed. As a
      conclusion, microbial metabolism could be directed by using mixtures of
      inexpensive saturated fats, glycerol, and glucose as co-substrates, in order to
      accumulate lipids with predetermined composition, e.g., cocoa-butter equivalents.

PMID- 12520369
TI  - Effect of plant growth-promoting Rhizobacteria and culture filtrate of Sclerotium
      rolfsii on phenolic and salicylic acid contents in chickpea (Cicer arietinum).
AB  - Two plant growth-promoting rhizobacteria (PGPR), viz., Pseudomonas fluorescens
      strain Pf4 and P. aeruginosa strain Pag, protected chickpea ( Cicer arietinum)
      plants from Sclerotium rolfsii infection when applied singly or in combination as
      seed treatment. Pag gave the best protection to the seedlings, applied either
      singly (mortality 16%) or in combination with Pf4 (mortality 17%) compared with
      44% and 24% mortality in control and Pf4 treatment, respectively. The two PGPR
      strains induced the synthesis of specific phenolic acids, salicylic acid (SA), as
      well as total phenolics at different growth stages of chickpea seedlings with
      varied amount. The maximum amount of total phenolics was recorded in all the
      aerial parts of 4-week-old plants. Gallic, ferulic, chlorogenic, and cinnamic
      acids were the major phenolic acids detected in high-performance liquid
      chromatography (HPLC) analysis. Induction of such phenolic acids in the seedlings
      was observed up to 6 weeks in comparison with control. Salicylic acid (SA) was
      induced frequently during the first 3 weeks of growth only. Between the two
      strains, Pag was more effective in inducing phenolic acid synthesis applied
      either singly or in combination with strain Pf4 during the entire 6 weeks of
      growth of chickpea. In the presence of a culture filtrate of S. rolfsii, the two
      Pseudomonas strains induced more phenolic acids in treated than in non-treated
      and control plants. The occurrence of salicylic acid was frequent in the first 24
      h, but infrequent at 48 and 96 h. Foliar spray of Pseudomonas strains also
      enhanced the phenolic acid content as well as total phenolics within 24 h of
      application. Gallic, chlorogenic, and cinnamic acids were consistently discerned
      in the treated leaves, whereas SA was absent even up to 96 h of application.
      Resistance in chickpea plants by Pseudomonas strains through induction of
      phenolic compounds as well as induced systemic resistance via SA-dependent
      pathway was evident.

PMID- 12520370
TI  - Glucose fermentation by Propionibacterium microaerophilum: effect of pH on
      metabolism and bioenergetic.
AB  - pH affected significantly the growth and the glucose fermentation pattern of
      Propionibacterium microaerophilum. In neutral conditions (pH 6.5-7.5), growth and
      glucose fermentation rate (qs) were optimum producing propionate, acetate, CO(2),
      and formate [which together represented 90% (wt/wt) of the end products], and
      lactate representing only 10% (wt/wt) of the end products. In acidic conditions,
      propionate, acetate, and CO(2) represented nearly 100% (wt/wt) of the
      fermentation end products, whereas in alkaline conditions, a shift of glucose
      catabolism toward formate and lactate was observed, lactate representing 50%
      (wt/wt) of the fermentation end products. The energy cellular yields ( Y(X/ATP)),
      calculated (i) by taking into account extra ATP synthesized through the reduction
      of fumarate into succinate, was 6.1-7.2 g mol(-1). When this extra ATP was
      omitted, it was 11.9-13.1 g mol(-1). The comparison of these values with those of
      Y(X/ATP) in P. acidipropionici and other anaerobic bacteria suggested that P.
      microaerophilum could not synthesize ATP through the reduction of fumarate into
      succinate and therefore differed metabolically from P. acidipropionici.

PMID- 12520371
TI  - Carbon and pH modulate the expression of the fungal glucose repressor encoding
      genes.
AB  - The phytopathogenic necrotrophic fungus Sclerotinia sclerotiorum secretes large
      amounts of oxalic acid and cell wall-degrading enzymes (CWDE). Enzyme synthesis
      is pH dependent and subject to carbon catabolite repression. Because of the
      possible involvement of the glucose repressor CRE1 in the transcriptional control
      of the CWDE encoding genes, we studied crel expression with respect to the nature
      of the extracellular carbon source and the value of the external pH. Comparative
      analysis of the cre1 homologous gene creA from Aspergillus nidulans was performed
      with pH-deregulated mutants. The data obtained showed that ambient pH controls
      the expression level of the carbon repressor genes, and this control does not
      depend on the pH transcription factor PacC.

PMID- 12520372
TI  - The survival of ingested Serratia marcescens in houseflies (Musca domestica L.)
      after electrocution with electric fly killers.
AB  - Electric fly killers (EFKs) are commonly used to control flying insects that
      enter food establishments. For establishment of the incidence of pathogen-bearing
      insects in food establishments, insect samples obtained from EFK trays could be
      used. The principal difficulty with this approach is that the survival time of
      microorganisms on or within insect corpses after electrocution is unknown. This
      study determined the survival of Serratia marcescens (as a representative of the
      enteric bacteria) within houseflies following their electrocution by a commercial
      EFK. S. marcescens was successfully ingested by houseflies and survived on and
      within the corpses after electrocution for up to 5 weeks. Maximal levels of
      bacteria were recovered 24 h postelectrocution. The study also demonstrates the
      ability of ingested S. marcescens to out-compete resident microbial flora within
      houseflies. The findings are intended to pave the way for further research to
      determine the incidence of pathogen-laden flying insects in food establishments.

PMID- 12520373
TI  - Shifting priorities at the Department of Energy's bomb factories: protecting
      human and ecological health.
AB  - More than 50 years of research, development, manufacture, and testing of nuclear
      weapons at Department of Energy (DOE) sites has left a legacy of on-site
      contamination that often spreads to surrounding areas. Despite substantial
      cleanup budgets in the last decade, the DOE's top-to-bottom review team concluded
      that relatively little actual cleanup has been accomplished, although milestones
      have been met and work packages completed. Rather than solely use regulatory
      constraints to direct cleanup, many people have suggested that human and
      ecological health should guide long-term stewardship goals of DOE-managed sites.
      The main questions are how ecological and human health considerations should be
      applied in deciding the extent of cleanup that contaminated sites should receive
      and how near-term and longer run considerations of costs and benefits should be
      balanced as cleanup decisions are made. One effort to protect ecological
      integrity is the designation of the largest sites as National Environmental
      Research Parks (NERPs). Recently, the Competitive Enterprise Institute (CEI)
      suggested isolating and conserving DOE sites as a policy priority because of
      their rich ecological diversity. A more effective long-term stewardship approach
      for former nuclear weapons complex sites may emerge if the guiding principles are
      to (1) reduce risks to human and ecological health, (2) protect cultural
      traditions, and (3) lower short- and long-term cleanup and remediation costs. A
      "net benefits" perspective that takes both near- and longer-term costs and
      consequences into account can help illuminate the trade-offs between expensive
      cleanup in the near term and the need to assure long-term protection of human
      health, cultural values, and high levels of biodiversity and ecological integrity
      that currently exist at many DOE sites.

PMID- 12520375
TI  - Soft systems methodology and the ecosystem approach: a system study of the Cooum
      River and environs in Chennai, India.
AB  - This paper discusses the integration of soft systems methodology (SSM) within an
      ecosystem approach in research to support rehabilitation and management of the
      Cooum River and environs in Chennai, India. The Cooum is an extremely polluted
      urban stream. Its management is complicated by high rates of population growth,
      poverty, uncontrolled urban development, jurisdictional conflicts, institutional
      culture, flat topography, tidal action, blockage of the river mouth, and monsoon
      flooding. The situation is characterized by basic uncertainty about main
      processes and activities, and the nature of relationships among actors and
      elements in the system.SSM is an approach for dealing with messy or ill
      structured problematic situations involving human activity. In this work SSM
      contributed techniques (such as "rich picture" and "CATWOE" tools) to description
      of the Cooum situation as a socioecological system and informed the approach
      itself at a theoretical level. Application of three general phases in SSM is
      discussed in the context of the Cooum River research: (1) problem definition and
      exploration of the problem situation, (2) development of conceptual models of
      relevant systems, and (3) the use of these to generate insight and stimulate
      debate about desirable and feasible change. Its use here gives weight to the
      statement by others that SSM would be a particularly appropriate methodology to
      operate the ecosystem approach. As well as informing efforts at management of the
      Cooum system, this work led the way to explore an adaptive ecosystem approach
      more broadly to management of the urban environment for human health in Chennai.

PMID- 12520374
TI  - Local peoples' knowledge, aptitude and perceptions of planning and management
      issues in nanda devi biosphere reserve, India.
AB  - Local peoples' knowledge, aptitude, and perceptions of planning and management
      issues were investigated in Nanda Devi Biosphere Reserve (NDBR) in Uttaranchal
      State of India. Conflicts ensued between local inhabitants and the management
      authority due to lack of community participation. Although most respondents seem
      to claim the knowledge of the objectives of Nanda Devi Biosphere Reserve, the
      source of information indicates their interaction with the management authority
      is not frequent. While local population seem to agree on reduced intensity of
      agriculture with compensation equal to loss of net income, there is a perceptible
      difference in responses among different age groups. While the younger generation
      seems to agree to move away to other areas with suitable compensation packages,
      the older generation prefer those options that require some adjustments in use
      and access to natural resources. The option of ecotourism as a source of income
      is acceptable to most respondents, but young and old respondents disagreed about
      impact of such activity on social behavior of local inhabitants. Among those
      groups studied, only the "self-employed group" seem to be more interested in
      ecotourism in comparison to other occupation classes. Gender differences in
      perceptions are prominent with reference to development options. While the men
      preferred economic opportunities, the women preferred improved living conditions.
      An evaluation mechanism similar to the one described in this paper will be
      helpful to the management authority to assess and modify their management plans
      to mitigate conflicts with local people.

PMID- 12520376
TI  - Lakes, wetlands, and streams as predictors of land use/cover distribution.
AB  - The importance of the surrounding landscape to aquatic ecosystems has been well
      established. Most research linking aquatic ecosystems to landscapes has focused
      on the one-way effect of land on water. However, to understand fully the complex
      interactions between aquatic and terrestrial ecosystems, aquatic ecosystems must
      be seen not only as receptors of human modification of the landscape, but also as
      potential drivers of these modifications. We hypothesized that the presence of
      aquatic ecosystems influences the spatial distribution of human land use/cover of
      the nearby landscape (</=1 km) and that this influence has changed through time
      from the 1930s to the 1990s. To test this hypothesis, we compared the
      distribution of residential, agricultural, and forested land use/cover around
      aquatic ecosystems (lakes, wetlands, and streams) to the overall regional land
      use/cover proportion in an area in southeast Michigan, USA; we also compared the
      distribution of land use/cover around county roads/highway and towns (known
      determinants of many land use/cover patterns) to the regional proportion. We
      found that lakes, wetlands, and streams were strongly associated with the
      distribution of land use/cover, that each ecosystem type showed different
      patterns, and that the magnitude of the association was at least as strong as the
      association with human features. We also found that the area closest to aquatic
      ecosystems (<500 m) was more strongly associated with land use/cover distribution
      than areas further away. Finally, we found that the strength of the association
      between aquatic ecosystems and land use/cover increased from 1938 to 1995,
      although the overall patterns were similar through time. Our results show that a
      more complete understanding is needed of the role of aquatic ecosystems on the
      distribution of land use/cover.

PMID- 12520377
TI  - Physiological and morphological response patterns of Populus deltoides to
      alluvial groundwater pumping.
AB  - We examined the physiological and morphological response patterns of plains
      cottonwood [ Populus deltoides subsp. monilifera (Aiton) Eck.] to acute water
      stress imposed by groundwater pumping. Between 3 and 27 July 1996, four large
      pumps were used to withdraw alluvial groundwater from a cottonwood forest along
      the South Platte River, near Denver, Colorado, USA. The study was designed as a
      stand-level, split-plot experiment with factorial treatments including two soil
      types (a gravel soil and a loam topsoil over gravel), two water table drawdown
      depths ( approximately 0.5 m and >1.0 m), and one water table control (no
      drawdown) per soil type. Measurements of water table depth, soil water potential
      (Psi(s)), predawn and midday shoot water potential (Psi(pd) and Psi(md)), and D/H
      (deuterium/hydrogen) ratios of different water sources were made in each of six
      600-m(2) plots prior to, during, and immediately following pumping. Two
      additional plots were established and measured to examine the extent to which
      surface irrigation could be used to mitigate the effects of deep drawdown on P.
      deltoides for each soil type. Recovery of tree water status following pumping was
      evaluated by measuring stomatal conductance ( g(s)) and xylem water potential
      (Psi(xp)) on approximately hourly time steps from before dawn to mid-afternoon on
      11 August 1996 in watered and unwatered, deep-drawdown plots on gravel soils. P.
      deltoides responded to abrupt alluvial water table decline with decreased shoot
      water potential followed by leaf mortality. Psi(pd) and percent leaf loss were
      significantly related to the magnitude of water table declines. The onset and
      course of these responses were influenced by short-term variability in surface
      and ground water levels, acting in concert with physiological and morphological
      adjustments. Decreases in Psi(pd) corresponded with increases in Psi(md),
      suggesting shoot water status improved in response to stomatal closure and crown
      dieback. Crown dieback caused by xylem cavitation likely occurred when Psi(pd)
      reached -0.4 to -0.8 MPa. The application of surface irrigation allowed trees to
      maintain favorable water status with little or no apparent cavitation, even in
      deep-drawdown plots. Two weeks after the partial canopy dieback and cessation of
      pumping, g(s) and Psi(xp) measurements indicated that water stress persisted in
      unwatered P. deltoides in deep-drawdown plots.

PMID- 12520378
TI  - Response of three plant communities to trampling in a sand dune system in
      brittany (france).
AB  - Dunes that are protected because of their very rich and diverse plant communities
      are often exposed to excessive visitor pressure. The effects of trampling on the
      habitat must be known from a conservation viewpoint but also are important for
      management. To determine the response of plant assemblages to trampling by
      people, an experimental study was conducted on the state-owned dunes at Quiberon
      (Brittany, France). Indices of resistance and resilience were used to compare
      three typical plant communities belonging to the various landscape units: mobile
      dune, semifixed dune, and fixed dune. The strong contrasts between communities
      belonging to different successional stages reflect their ecological functioning.
      The mobile dune and semifixed dune with their low resistance contrasted with the
      fixed dune. Only the vegetation cover of the semifixed dune benefited from long
      term trampling and had a very high resilience (134%). This response could be
      explained by a good balance of two opposite factors: soil compaction increasing
      soil stability and moisture content, and vegetation destruction. Because of their
      low resilience, trampling seems to be harmful for fixed dunes in the long term.
      The tourist pressure seems easier to integrate in to the mobile dunes and the
      semifixed dunes if periods of recovery are included in the management.

PMID- 12520379
TI  - Recovery trajectories after in situ burning of an oiled wetland in coastal
      Louisiana, USA.
AB  - The high degree of physical disturbance associated with conventional response
      options to oil spills in wetlands is driving the investigation of alternative
      cleanup methodologies. In March 1995, a spill of gas condensate in a brackish
      marsh at Rockefeller Wildlife Refuge in southwestern Louisiana was remediated
      through the use of in situ burning. An assessment of vegetation recovery was
      initiated in three treatment marshes: (1) oil-impacted and burned, (2) oil
      impacted and unburned, and (3) a nonoiled unburned reference. We compared percent
      cover, stem density, and biomass in the treatment marshes to define ecological
      recovery of the marsh vegetation and soil hydrocarbon content to determine the
      efficacy of in situ burning as a cleanup technique. Burning led to a rapid
      decrease in soil hydrocarbon concentrations in the impacted-and-burned marsh to
      background levels by the end of the first growing season. Although a management
      fire accidentally burned the oil-impacted-and-unburned and reference marshes in
      December 1995, stem density, live biomass, and total percent cover values in the
      oil-impacted-and-burned marsh were equivalent to those in the other treatment
      marshes after three years. In addition, plant community composition within the
      oil-impacted-and-burned marsh was similar to the codominant mix of the grasses
      Distichlis spicata (salt grass) and Spartina patens (wire grass) characteristic
      of the surrounding marsh after the same time period. Rapid recovery of the oil
      impacted-and-unburned marsh was likely due to lower initial hydrocarbon exposure.
      Water levels inundating the soil surface of this grass-dominated marsh and the
      timing of the in situ burn early in the growing season were important factors
      contributing to the rapid recovery of this wetland. The results of this in situ
      burn evaluation support the conclusion that burning, under the proper conditions,
      can be relied upon as an effective cleanup response to hydrocarbon spills in
      herbaceous wetlands.

PMID- 12520380
TI  - Land-cover assessment of conservation and buffer zones in the BOSAWAS natural
      resource reserve of Nicaragua.
AB  - The BOSAWAS Natural Resource Reserve of Nicaragua was established in 1991, to
      protect a portion of the remaining tropical rain forest and to promote the
      sustainable use of the region's resources. Information required to effectively
      manage the reserve includes the extents and locations of present land-cover types
      and recent land-cover changes in the management use zones that were delineated by
      local indigenous communities. These zones include areas designated for
      conservation, limited resource extraction, agriculture, and watershed protection.
      Land-cover for 1986 and 1995 was identified for three of the communities from
      remotely sensed images and then input into a geographic information system
      database to identify land-cover types within these management use zones. For both
      dates of the analysis, advanced forest was the dominant land cover, with the
      conservation zones entirely forested. The amount of both agricultural land and
      scrub/early secondary forest increased between the two dates, with much of these
      land-cover classes occurring in the agriculture zones. Conflicts between the land
      cover present and designated use were identified in some of the limited-use
      buffer and watershed protection zones. Changes between 1986 and 1995 were
      identified by overlaying the two land-cover data sets. Three change processes
      were identified as occurring: deforestation, reforestation, and reconversion.
      Changes were concentrated in the agriculture zones but were found to occur in
      every type of zone, except for conservation. The results of this study will
      establish baseline information for the future management of the BOSAWAS Reserve,
      an important component in uniting conservation areas along the Central American
      isthmus.

PMID- 12520381
TI  - Introduced species and management of a Nothofagus/Austrocedrus forest.
AB  - Isla Victoria (Nahuel Huapi National Park, Argentina), a large island dominated
      by native Nothofagus and Austrocedrus forest, has old plantations of many
      introduced tree species, some of which are famed invaders of native ecosystems
      elsewhere. There are also large populations of introduced deer and shrubs that
      may interact in a complex way with the introduced trees, as well as a recently
      arrived population of wild boar. Long-standing concern that the introduced trees
      will invade and transform native forest may be unwarranted, as there is little
      evidence of progressive invasion, even close to the plantations, despite over 50
      years of opportunity. Introduced and native shrubs allow scattered introduced
      trees to achieve substantial size in abandoned pastures, but in almost all areas
      neither the trees nor the shrubs appear to be spreading beyond these sites. These
      shrub communities may be stable rather than successional, but the technology for
      restoring them to native forest is uncertain and probably currently impractical.
      Any attempt to remove the exotic tree seedlings and saplings from native forest
      would probably create the very conditions that would favor colonization by exotic
      plants rather than native trees, while simply clear-cutting the plantations would
      be unlikely to lead to regeneration of Nothofagus or Austrocedrus. The key to
      maintaining native forest is preventing catastrophic fire, as several introduced
      trees and shrubs would be favored over native dominant trees in recolonization.
      Deer undoubtedly interact with both native and introduced trees and shrubs, but
      their net effect on native forest is not yet clear, and specific management of
      deer beyond the current hunting by staff is unwarranted, at least if preventing
      tree invasion is the goal. The steep terrain and shallow soil make the recently
      arrived boar a grave threat to the native forest. Eradication is probably
      feasible and should be attempted quickly.

PMID- 12520382
TI  - SO2 dispersion and monthly evaluation of the industrial source complex short-term
      (ISCST32) model at Mina Al-Fahal refinery, Sultanate of Oman.
AB  - Modeling of air pollutant dispersion has been undertaken for emissions of sulfur
      dioxide (SO(2)) at the Mina Al-Fahal refinery in the Sultanate of Oman. The study
      was conducted during the period of November 1999 to October 2000. The Industrial
      Source Complex Short-Term (ISCST32) air pollution model was adopted to predict
      the ground level concentration of SO(2) in and around the refinery. The modeling
      results were validated against measured data during the study period. The
      comparison, based on the monthly average measurements, showed that the model
      underestimates the observed SO(2) concentrations. However, the predicted ground
      level concentrations of SO(2) during the months of September, October, November,
      and June were in better agreement with the observations. The predicted SO(2)
      values are presented in the form of concentration contours to determine the
      spatial distribution of SO(2) and to assess the impact on air quality over the
      survey area. Predicted SO(2) concentrations were found lower than the World
      Health Organisation (WHO) guideline value of 365 microg/m(3), with the maximum
      ground level concentrations being found to occur relatively close to the sources
      of emission. Moreover, concentration contour patterns for the modeled area vary
      with changes in meteorological conditions. On the basis of this study, the
      refinery is not likely to cause any significant deterioration in air quality, and
      predicted concentrations of SO(2) are well below those likely to influence
      health.

PMID- 12520383
TI  - Additivity of state inventories of greenhouse-gas emissions.
AB  - In addition to national inventories of emissions of greenhouse gases, there are
      inventories for most, but not all, states constituting the United States. This
      paper analyzes the state inventories to see if reported emissions of carbon
      dioxide, methane, and nitrous oxide are additive. Considerable reanalysis of the
      state inventories is required before they can be added to yield a larger-scale
      inventory. Some specific sources were considered by some states but not by
      others. Estimation techniques evolved over time as inventories were produced, and
      there are instances of both double-counting (two states reporting the same
      emission) and omission (neither state reporting the same emission), where
      interstate transfers of energy or materials occurred. Nevertheless, the
      inventories, when adjusted for obvious double-counting or omissions, are probably
      approximately additive, although it is difficult to quantify the extent to which
      this is true.

PMID- 12520384
TI  - Prioritizing wetland restoration for sediment yield reduction: a conceptual
      model.
AB  - In a climate of limited resources, it is often necessary to prioritize
      restoration efforts geographically. The synoptic approach is an ecologically
      based tool for geographic prioritization of wetland protection and restoration
      efforts. The approach was specifically designed to incorporate best professional
      judgment in cases where information and resources are otherwise limited. Synoptic
      assessments calculate indices for functional criteria in subunits (watersheds,
      counties, etc.) of a region and then rank the subunits. Ranks can be visualized
      in region-scale maps which enable managers to identify areas where efforts
      optimize functional performance on a regional scale. In this paper, we develop a
      conceptual model for prioritizing watersheds whose wetlands can be restored to
      reduce total sediment yield at the watershed outlet. The conceptual model is
      designed to rank watersheds but not individual wetlands within a watershed. The
      synoptic approach is valid for applying the sediment yield reduction model
      because there is high demand for prioritizing disturbed wetlands for restoration,
      but there is limited, quantitative, accurate information available with which to
      make decisions. Furthermore, the cost of creating a comprehensive database is
      prohibitively high. Finally, because the model will be used for planning
      purposes, and, specifically, for prioritizing based on multiple decisions rather
      than optimizing a single decision, the consequence of prioritization errors is
      low. Model results cannot be treated as scientific findings. The conclusions of
      an assessment are based on judgement, but this judgement is guided by scientific
      principles and a general understanding of relevant ecological processes. The
      conceptual model was developed as the first step towards prioritizing of wetland
      restoration for sediment yield reduction in US EPA Region 4.

PMID- 12520385
TI  - Targeting cytokine/chemokine receptors: a challenge for molecular nuclear
      medicine.
AB  - Radiolabelled cytokines and chemokines are a group of radiopharmaceuticals that,
      by highlighting in vivo the binding to specific high-affinity receptors expressed
      on selected cell populations, allow the molecular and functional characterisation
      of immune-mediated processes Recently, several authors have described the use of
      radiolabelled cytokines and chemokines not only for imaging of inflammation and
      infection, but also as an approach to study in vivo the biology of primary and
      metastatic cancer cells. The latter avenue of research has been pursued
      particularly to help oncologists in therapeutic decision making and to follow up
      the efficacy of new immune therapies. In this paper we describe the
      characteristics of cytokines and chemokines, focussing on their role as
      radiopharmaceuticals for the imaging of cancer cells in vivo, a new challenge for
      molecular nuclear medicine.

PMID- 12520386
TI  - Direct and indirect exogenous contamination by pesticides of rice-farming soils
      in a Mediterranean wetland.
AB  - It is known that the sources of soil contamination can be endogenous or exogenous
      and that exogenous contamination may be direct or indirect. In this work, an
      environmental pesticide fate study was conducted in soil profiles collected from
      23 rice field sites in an important Mediterranean wetland (Albufera Natural Park,
      Valencia, Spain) from April 1996 to November 1997. Temporal and spatial
      distribution of 44 pesticide residues in an alluvial Mediterranean soil (gleyic
      calcaric Fluvisol, Fluvaquent) were monitored. During this period, the levels of
      pesticide residues in different soil horizons (Ap1 0-12 cm, Ap2 12-30 cm, ApCg 30
      50 cm, C1gr 50-76 cm, and C2r 76-100 cm) were investigated. In addition,
      information was collected on agricultural pesticide application practices and
      soil characteristics. Distribution throughout the soil profile showed that
      pesticide concentrations were always higher in the topsoil (Ap1 horizon), in the
      autumn season, and in the border with citrus-vegetable orchard soils (calcaric
      Fluvisol, Xerofluvent). Chlorpyrifos (organophosphorus), endosulfan
      (organochlorine), and pyridaphenthion (organophosphorus) insecticides were,
      respectively, the most detected of all the pesticides investigated. These results
      were associated with processes, such as nonleaching, transport by movement into
      surface waters, retention, volatilization, and chemical and biological
      degradation in the topsoil, as well as with direct and indirect exogenous
      contamination sources.

PMID- 12520387
TI  - Statistical implications of pyrene and phenanthrene sorptive phenomena: effects
      of sorbent and solute properties.
AB  - A 3 x 2 factorial experiment in a generalized randomly complete block was
      conducted to assess the effects of soil type, soil preparation, and solute
      concentration on the sorptive behavior of pyrene (PYR) and phenanthrene (PHE).
      Three bulk soils were treated to remove the soil organic matter (SOM) or clay
      fractions, then spiked with an initial PYR/PHE concentration of either 3 or 15
      mg/L. On average, 98.3% PYR and 91.3% PHE were sorbed to the bulk soils in 24 h,
      with 4.96 mg PYR kg(-1) soil and 22.48 mg PHE kg(-1) soil desorbed after three
      successive 24-h desorption steps. Both clay minerals and SOM greatly contributed
      to the sorptive behavior. For example, an average 95.1% and 96.1% of the initial
      PYR sorbed to the clay-removed and SOM-removed subsoils, respectively.
      Conversely, 16.5 mg/kg and 12.9 mg/kg of the sorbed PYR was desorbed from the
      clay-removed and SOM-removed subsoils, respectively.

PMID- 12520388
TI  - Distribution of heavy metals in the street dusts and soils of an industrial city
      in northern Spain.
AB  - This study characterizes the elemental composition of street dust and soils in
      Aviles (N. Spain), a medium-size city of approximately eighty thousand
      inhabitants, where industrial activities and traffic strongly affect heavy metal
      distribution. A total of 112 samples of street dust were collected within a 7
      km(2) area, encompassing residential and industrial sites (ferrous and non
      ferrous plants). Elevated geometric mean concentrations of zinc (4,892 microg x
      g(-1)), cadmium (22.3 microg x g(-1)), and mercury (2.56 microg x g(-1)) in
      street dust were found in samples located near industrial areas. Two types of
      anthropic influence were distinguishable: the first and most important one is
      that related to metallurgical activity and transportation of raw materials for
      local industries. Secondly, exhaust emissions from traffic are an important
      source of lead concentration in areas with high vehicular density (geometric
      mean: 514 microg x g(-1)). The zinc content in the dust samples decreased with
      the distance from a zinc smelter located in the northern part of the city. The
      same trend was found for other elements in association with zinc in the raw
      materials used by the smelter, such as cadmium and mercury. A simultaneous
      research campaign of urban soils, that involved the collection of 40 samples from
      a 10-km(2) area, revealed geometric mean concentrations of 376 microg x g(-1) Zn,
      2.16 microg x g(-1) Cd, 0.57 microg x g(-1) Hg, and 149 microg x g(-1) Pb, and
      distribution patterns almost identical to those found for street dust.

PMID- 12520389
TI  - Assessment of organochlorine pesticide residues in West African city farms:
      Banjul and Dakar case study.
AB  - Validated analytical procedures for the determination of 21 organochlorine
      pesticides have been applied to 74 water samples, 76 soil samples, and 160
      vegetable samples from nine Sene-Gambian farms. Mean pesticide residue levels
      found were compared to the results of other studies. The main contaminants were
      DDTs in water (231.9 ng/L), in soil (71.4 ng/g), and in vegetables (5.03 ng/g).
      The distribution of pesticide residues in water and neighboring soils and the
      soil-plant transfer of these pesticides is briefly discussed. Different
      bioconcentration factors for sum HCHs, sum DDTs, and sum endosulfans obtained in
      this study allow us to confirm the complex processes already reported in the
      literature concerning the uptake and translocation of chemicals from soil to
      plant.

PMID- 12520390
TI  - The concentrations and bioconcentration factors of copper and zinc in edible
      mushrooms.
AB  - Copper and zinc contents have been determined in up to 28 species of edible
      mushrooms from different sites in the province of Lugo (NW Spain). Two hundred
      thirty-eight collected samples were analyzed by an anodic stripping voltammetric
      technique using a drop mercury as the working electrode. The results showed that
      the element concentrations were species-dependent, and the highest metal levels
      corresponded to the following species: Calvatia utriformis (235.5 mg Cu/kg),
      Macrolepiota procera (217.8 mg Cu/kg), and Agaricus macrosporus (217.7 mg Cu/kg)
      and Calvatia utriformis (265.8 mg Zn/kg), Lactarius delicious (231.0 mg Zn/kg),
      and Agaricus macrosporus (221.3 mg Zn/kg) for Cu and Zn, respectively. All
      mushroom species bioaccumulated copper and zinc. Nevertheless, some individual
      samples of the species, such as Hydnum repandum, Cantharellus cibarius, and
      Coprinus comatus, were bioexclusors (BCF < 1). The hymenophore in mushrooms
      showed higher mean metal levels than the rest of the fruit bodies, with
      statistically significant differences. The copper and zinc concentrations were
      compared to literature data and levels set by legislation. It can be concluded
      that the consumption of these mushrooms cannot be considered a toxicological
      risk, and they provide an important nutritional requirement to the diet.

PMID- 12520391
TI  - Impacts of Cd and Zn on the development of periphytic diatom communities in
      artificial streams located along a river pollution gradient.
AB  - Many field and experimental studies have been conducted to reveal modifications
      of periphytic diatom communities under metal pollution, but most of the
      approaches presented drawbacks: variability of environmental factors for field
      studies and lack of representativity for experimental ones. An original approach
      that allows growth of periphytic communities under conditions more controlled
      than in the field and more realistic than experimental investigations was
      developed to try conclusions being drawn on the real impact of metallic
      pollution. Artificial streams were placed on the river bank at three sites along
      the pollution gradient (Cd/Zn) of the River Lot (SW France): reference (upstream
      pollution discharge), slightly polluted (around 1.5 microg Cd x L(-1) and 50
      microg Zn x L(-1)), and polluted (around 6 microg Cd x L(-1) and 400 microg Zn x
      L(-1)) sites. Structural characteristics of diatom communities growing in these
      artificial streams, on glass substrates, and under homogenized current velocity
      and water depth were compared after four durations (1, 2, 3, and 4 weeks) to
      study effects of metal on first steps of community development. Marked
      perturbations of diatom community development were observed overall in the
      polluted site: after 1 week, early biofilms differed already by taxonomic
      composition; after 4 weeks, cell density was significantly lower than in the
      reference site and taxonomic composition was very different. These results,
      generated by a methodology intermediate between field and experimental
      approaches, compare well with literature findings based on more traditional
      approaches, strongly attesting that metallic pollution affects diatom community
      architecture and induce rising of abnormal cells.

PMID- 12520392
TI  - Phytotoxicity of 2,4,6-trinitrotoluene (TNT) and octahydro-1,3,5,7-tetranitro
      1,3,5,7-tetrazocine (HMX) in spiked artificial and natural forest soils.
AB  - Toxicity of 2,4,6-trinitrotoluene (TNT) and octahydro-1,3,5,7-tetranitro-1,3,5,7
      tetrazocine (HMX) using two terrestrial plant species, lettuce (Lactuca sativa)
      and barley (Hordeum vugare), was assessed in artificial soil (silica) and forest
      soil. Lettuce emergence was significantly decreased after 5 days of exposure to
      TNT nominal spiked concentrations >/= 1,040 mg/kg dry soil in silica. Barley
      emergence was significantly reduced after 14 days of exposure at initial (t = 0)
      TNT concentrations >/= 55.9 +/- 4.5 mg/kg dry soil in silica and at >/= 291.9 +/-
      42.8 mg/kg dry forest soil. Biomasses of shoot and roots of barley seeds were
      significantly reduced after 14 days of exposure at TNT initial exposure
      concentrations >/= 55.9 +/- 4.5 (LOEC) mg/kg dry soil in silica. Results were
      similar with the forest soil (LOEC = 91.4 +/- 7.9 mg TNT/kg dry soil) using the
      root growth parameter, but the shoot biomass was reduced only at concentrations
      >/= 291.9 +/- 42.8 mg TNT/kg dry soil. Plants were not affected by an HMX
      exposure up to 3,320 +/- 1,019 mg/kg dry soil using silica or 1,866 +/- 438 mg/kg
      dry soil using a forest soil. During the 14-day experiments, TNT was partially
      transformed in the spiked soil samples, as indicated by the presence of its amino
      metabolites (2-ADNT and 4-ADNT). Higher quantities of metabolites were detected
      in forest soils having higher initial TNT concentrations (</= 1,849.4 +/- 228.2
      mg/kg) compared to silica (</= 239.3 +/- 88.0 mg TNT/kg). After 14 days, TNT
      concentrations in spiked silica and forest soil were reduced up to 80.5% at 55.9
      +/- 4.5 mg/kg initial concentration and 94.4% at 91.4 +/- 7.9 mg/kg initial
      concentration, respectively. Data indicate that TNT is the probable phytotoxicant
      because it decreased plant emergence and growth in the presence and absence of
      the ADNT metabolites.

PMID- 12520393
TI  - The combined effects of hardness, pH, and dissolved organic carbon on the chronic
      toxicity of Zn to D. magna: development of a surface response model.
AB  - The effect of changes in pH, hardness, and dissolved organic carbon (DOC) and the
      possible interactions among these parameters on the chronic toxicity of zinc to
      D. magna were investigated. Based on a Central Composite Design, models were
      developed that can explain the observed variation in EC(10) and EC(50) as a
      function of these toxicity modifying factors. All three parameters significantly
      altered the observed effect concentrations based on net reproductive rate. The
      largest differences in 21-day EC(10)s and EC(50)s caused by these factors were
      10.1 and 4.9, respectively. An increase in pH and/or DOC decreased zinc toxicity.
      The significant interaction between pH and DOC on observed chronic Zn toxicity is
      in accordance with earlier reported increased sorption efficiency of Zn to humic
      substances at higher pH levels. Lowest Zn toxicity was observed in tests
      performed with moderately hard test media (between 200 and 300 mg/L as CaCO(3)).
      Lower or higher hardness of the test medium resulted in lower effect
      concentrations. Based on physico-chemical characteristics of the test media,
      developed models can be used to explain the variation between reported NOECs for
      Zn and may improve current environmental risk assessment procedures of metals.

PMID- 12520394
TI  - A comparison of the metal content of some benthic species from coastal waters of
      the Florida panhandle using high-resolution inductively coupled plasma mass
      spectrometry (ICP-MS) analysis.
AB  - Benthic marine invertebrates, sediment, and water from several locations along
      the Florida panhandle coast from St. Joseph Bay in the west to the mouth of the
      Wakulla River in the east, including from several river estuaries, were analyzed
      by double focusing ICP-MS (Finnigan MAT ELEMENT) for Cd, Hg, Pb, Cu, Zn, and As.
      All were detected in all samples. Sponges generally contained higher levels of Cd
      than other species. Microciona prolifera sponges from St. Joseph Bay had higher
      As levels (8.1-13.6 microg/g dry weight) than sponges collected from Dickerson
      Bay or Appalachee Bay (2.20-9.7) and higher Cd levels (0.43-0.73) than that of a
      single Microciona specimen collected from Dickerson Bay (0.29). Water content of
      As was about 20-30x higher in St. Joseph Bay than in any other location, and
      sediment levels of Cd were about 9x higher. Cu and Zn were higher in organic
      sediment from St. Joseph Bay than they were in other areas. The Pb content of
      several sponge species and two of tunicates was considerably higher than in other
      species. The uptake of most metals in this study (except As) appeared to be
      affected by the metal, genus, species, and location as much as by levels in
      either water or sediment. In general, sponges and tunicates seemed to accumulate
      higher levels than most other species, possibly a function of high filtration
      rates. The ICP-MS method is useful for environmental studies, but the instrument
      requires considerable maintenance.

PMID- 12520395
TI  - PCB and PCDD/F totals, TEQs, and congener patterns in Korean coastal marine
      environments, 1987, 1988, 1990, and 1996-1999.
AB  - Various mussel and oyster samples and select top sediment samples were taken over
      27 industrial and pristine coastal sites form South Korea's west, south, and east
      coasts. Site-specific total PCB, PCDD/F, and organochlorine TEQ levels in biota
      were 1-306 ng/g ww, 3-9,400 pg/g ww, and 0.3-200 pg/g ww, respectively. Temporal
      trends showed a general decrease in total TEQ with an increase in TEQ
      contribution by PCDD/Fs at most locations over the past decade. Linear regression
      was used to establish a relationship between each contaminant total and the
      respective TEQ contribution. Principal component analysis was used to model the
      congener-specific PCB and PCDD/F data, and two three-component models were
      developed that describe the congener-specific patterns based on the variance
      between samples over the entire data set. Unique PCDD/F patterns were identified
      and discussed with respect to outliers identified in the previously established
      TEQ regressions and a distinct PCDD/F pattern was found that related to a single
      industrial source (i.e., steel mill). PCB patterns were explored in relation to
      those of common commercial mixtures of PCBs (i.e., Aroclors) and patterns were
      discussed with respect to TEQ. It was found that sites with relatively high PCB
      TEQs showed an Aroclor 1254-like contamination.

PMID- 12520396
TI  - Bioconcentration and toxicity of dodecylbenzene sulfonate (C12LAS) to aquatic
      organisms exposed in experimental streams.
AB  - Fish, mollusks, and crustaceans were caged in the tail pool of streams during a
      C(12)LAS (dodecyl benzene sulfonate) model ecosystem experimental program.
      Bioconcentration of total C(12)LAS and individual isomers and acute and chronic
      toxicity were investigated during this study. Toxicity endpoints were based on
      water and tissue (i.e., body burden) concentrations at which adverse effects were
      observed. At 32 days, total C(12)LAS bioconcentration factors (BCFs) for the
      fathead minnow and three invertebrate species ranged from 9 to 116. In general,
      bioconcentration was affected by isomer position, exposure concentration, and
      species. BCF values tended to decrease as isomer position moved from external
      (e.g., 2-phenyl) to internal (e.g., 5,6-phenyl). BCFs also decreased as exposure
      concentration increased. Mean acute 4-d LC(50) values ranged from 1.5 to >3.0
      mg/L for the six species tested. Lethal body burdens associated with 50%
      mortality (LBB(50)) varied from 0.21 to 0.60 mmole/kg (wet weight). During the 32
      day chronic exposures, the EC(20) values were 0.27 (0.204-0.352), 0.95 (0.597
      1.29), and approximately 1.0 mg/L for Corbicula (length), Hyalella (survival),
      and fathead minnow (survival), respectively. At these EC(20) values, C(12)LAS
      body burdens were 0.035, 0.23, and 0.19 mmoles/kg wet weight in Corbicula,
      Hyalella, and fathead minnow, respectively. Fish exposed to wastewater treatment
      plant effluent had total C(12)LAS tissue concentrations ranging from 0.0005 to
      0.0039 mmoles/kg wet weight. These concentrations are approximately 45-360 times
      below the tissue concentration associated with subtle effects in the model
      ecosystem stream exposures. Total C(12)LAS body burdens in feral and caged
      Corbicula exposed to WWTP effluents were approximately 0.0013 mmoles/kg;
      approximately 25-fold below concentrations associated with effects in stream
      exposures.

PMID- 12520397
TI  - The effects of anti-androgenic and estrogenic disrupting contaminants on breeding
      gland (nuptial pad) morphology, plasma testosterone levels, and plasma
      vitellogenin levels in male Xenopus laevis (African clawed frog).
AB  - Nuptial pads are areas, digits, and forearm characterized by epidermal keratin
      hooks and dermal breeding glands opening on the epidermis surface in male frogs.
      The presence of the epidermal hooks and secretory activity of the breeding glands
      are androgen-dependent and considered functioning during mating. Chemical
      pollutants released into the aquatic environment by humans are suspected of
      disrupting the normal hormonal pathways and functioning. Among the best known of
      these endocrine-disrupting contaminants (EDCs) are compounds that mimic the
      steroid 17beta-estradiol. However, recently specific anti-androgenic activity by
      certain EDCs, including DDE and several fungicides, have been shown in mammalian
      studies. The African clawed frog, Xenopus laevis, has been proposed as an ideal
      species to be used as a model system for screening of endocrine disruptors. In
      this study we employed a newly developed ELISA for the measurement of plasma
      vitellogenin (VTG), normally produced in the liver of females under the influence
      of estrogens but also in males when exposed to exogenous estrogens. Furthermore,
      we investigated the potential of breeding (nuptial) gland activity to be employed
      as a biomarker system for screening for anti-androgenic activity by certain EDCs.
      Our results indicate that the pharmaceutic anti-androgen flutamide did
      significantly (p < 0.05) effect the androgen-dependent breeding (nuptial) glands
      and plasma testosterone concentrations in male X. laevis. Our results further
      confirm that the dicarboximide fungicide vinclozolin mimics the anti-androgenic
      action of flutamide. Vinclozolin, however, did not significantly effect the
      plasma testosterone concentration. Results also confirm the ability of 17beta
      estradiol to stimulate production and release of VTG in the liver of male X.
      laevis, although we could not confirm the in vivo induction of VTG by estrogenic
      mimics octylphenol and nonylphenol. Although more dose-response research is
      needed, this preliminary study confirms the potential of VTG production and
      breeding gland activity as biomarkers to screen chemicals and environmental
      samples for estrogenic and anti-androgenic activity using X. laevis males.

PMID- 12520398
TI  - Embryotoxic thresholds of mercury: estimates from individual mallard eggs.
AB  - Eighty pairs of mallards ( Anas platyrhynchos) were fed an uncontaminated diet
      until each female had laid 15 eggs. After each female had laid her 15th egg, the
      pair was randomly assigned to a control diet or diets containing 5, 10, or 20
      microg/g mercury as methylmercury until she had laid a second set of 15 eggs.
      There were 20 pairs in each group. After the second set of 15 eggs, the pair was
      returned to an uncontaminated diet, and the female was permitted to lay another
      30 eggs. For those pairs fed the mercury diets, the even-numbered eggs were
      incubated and the odd-numbered eggs were saved for possible mercury analysis.
      Mercury in the even-numbered eggs was estimated as the average of what was in the
      neighboring odd-numbered eggs. Neurological signs of methylmercury poisoning were
      observed in ducklings that hatched from eggs containing as little as 2.3 microg/g
      estimated mercury on a wet-weight basis, and deformities were seen in embryos
      from eggs containing about 1 microg/g estimated mercury. Although embryo
      mortality was seen in eggs estimated to contain as little as 0.74 microg/g
      mercury, there were considerable differences in the sensitivity of mallard
      embryos, especially from different parents, with some embryos surviving as much
      as 30 or more microg/g mercury in the egg.

PMID- 12520399
TI  - Mercury occurrence in prothonotary warblers (Protonotaria citrea) inhabiting a
      National Priorities List site and reference areas in southern Alabama.
AB  - Mercury occurrence in prothonotary warblers (Protonotaria citrea) was evaluated
      over two years in southern Alabama. Mercury was found in warbler nestlings and
      adults inhabiting National Priority List (NPL) sites in McIntosh, Alabama. Food
      items that were collected from nestlings also contained elevated mercury. When
      mercury concentrations in soil, food, and nestling were plotted at each nest box
      location, the distribution of mercury in the three matrices yielded information
      that direct bioaccumulation factors could not. There were site differences in
      mercury accumulation in nestlings inhabiting the NPL sites. Nestling mercury
      accumulation correlated with solid mercury concentrations near the nest box where
      the nestling was raised. Trophic transport of mercury was poorly defined by
      mercury in food; however, closer examination of prey items shows that food source
      influences accumulation. Mercury distributions in matrices provide useful
      information of uptake that can be integrated with risk assessment endpoints.

PMID- 12520400
TI  - Biological effects of gestational and lactational PCB exposure in neonatal and
      juvenile C57BL/6 mice.
AB  - The purpose of this study was to obtain a better understanding of polychlorinated
      biphenyl (PCB) immunotoxicity in the developing mouse. Adult female mice were
      dosed with three subcutaneous injections per week of 50 mg/kg Aroclor 1242
      (A1242), Aroclor 1254 (A1254), or corn oil for 2 weeks and then mated with
      nondosed males. First-litter pups were sacrificed at 7 or 28 days of age. At both
      ages, the tissue concentration of PCB was significantly higher in both the A1242
      and A1254 pups than in oil-treated controls. Seven-day-old pups exposed to A1242
      or A1254 had significantly decreased splenic IL-2 production. Alterations in the
      percentages of T cell subsets compared to controls were observed in A1242-exposed
      pups; an increased spleen somatic index was noted only in A1254-exposed pups.
      Twenty-eight-day-old pups exposed to A1254 demonstrated a significant decrease in
      thymus somatic index, an increase in liver somatic index, a 25% decrease in total
      circulating T(4), and decreased B cell percentages relative to their controls.
      Alteration in the percentages of CD3(int) T cells was observed in A1254-exposed
      28-day-old pups. A significant increase in 7-ethoxyresorufin- O-deethylase (EROD)
      and 7-benzoxyresorufin-O-dearylase (BROD) activity was measured at both ages in
      A1254-exposed pups and in A1242-exposed 28-day-old pups. These data confirm that
      during gestation and lactation A1242 and A1254 are transferred from dams to pups
      and that such exposure results in immune-related effects in neonatal (7-day-old)
      and juvenile (28-day-old) mice. Furthermore, A1254 exposure produces more
      frequent and pronounced effects than exposure to A1242.

PMID- 12520401
TI  - Interjoint coordination in lower limbs during different movements in humans.
AB  - Redundancy is associated with the ability of the nervous system to select
      different interjoint coordinations and movement trajectories to achieve the same
      motor goal. The nervous system may coordinate multiple degrees of freedom (DF) by
      combining them in a task-specific way to control them as a unit or synergy. Some
      movements may be accomplished using only one synergy, whereas other movements may
      employ several synergies. To investigate the problem of interjoint coordination,
      we applied principal component (PC) analysis to eight types of movement in
      healthy male subjects: forward squats, backward squats, sideways squats, squats
      on one leg, walking three steps, stepping in place, going up a step, and going
      down a step. Angular changes in four DF were analyzed: thigh flexion-extension,
      knee flexion-extension, ankle flexion-extension, thigh abduction-adduction, with
      the former three DF investigated in all movements. For many movements, two
      synergies were sufficient to account for more than 95% of DF angular excursions.
      Squatting on one leg could be described using only one synergy (99%). The angle
      between the vectors representing PCs for movements produced with the right and
      left legs could be less than 10 degrees for some movements but could reach 25
      degrees for other movements. The nervous system may thus use somewhat different
      interjoint coordinations while producing movements on the right and the left
      sides. The angle between the first PCs of different movements could be smaller
      than 10 degrees. Thus there may be a common but adjustable basic synergy that is
      used to produce different movements. Additional synergies provide the transition
      from one movement to another.

PMID- 12520402
TI  - The effects of graded compression of the median nerve in the carpal canal on grip
      force.
AB  - The relationship between tactile hypoesthesia and precision grip force was
      examined using compression of the median nerve in healthy adults. Hypoesthesia
      was graded by varying the pressure that an external clamp exerted over the carpal
      canal. Electrical stimulation of the median nerve in the forearm evoked a
      compound sensory nerve action potential (SNAP) that we recorded from the digital
      nerves of the index finger. Clamp pressure was varied to achieve SNAPs that were
      75%, 50%, and 25% of precompression amplitude (100%). Grip force and tactile
      sensibility (Semmes-Weinstein filaments, cotton wisps, sharp/dull) did not change
      in parallel with reductions of the SNAP. Subjects reported paresthesias at the
      thumb and index finger at 75% SNAP. Tactile pressure thresholds increased to the
      clinical range of 'diminished light touch', but subjects detected cotton wisps
      stroked along the finger. At 75% SNAP grip force did not change compared to 100%
      SNAP. Simple prehension can proceed efficiently despite these modest reductions
      in tactile signals. At 50% SNAP the digits remained sensate, but were reported to
      feel "thick, like cardboard". No subject could detect cotton wisps and tactile
      thresholds increased by one filament. Sharp/dull distinctions remained. Grip
      force increased by 55% compared to grip force at SNAPs of 100% and 75%. There
      were no changes in skin slipperiness, so the increased grip force represented
      elevated 'safety margin' (grip force exceeding that needed to prevent slip). At
      25% SNAP subjects described the skin innervated by the median nerve as feeling
      "numb", but grip force increased little compared to 50% SNAP. Grip force
      continued to reflect changes in grip surface friction, and mechanical transients
      from setting the object on the table triggered coordinated reductions in grip
      force. We suspect that the loss of information from SA I and FA I, but not FA II,
      tactile afferents provoked the increased grip force.

PMID- 12520403
TI  - Cross-axis adaptation of torsional components in the yaw-axis vestibulo-ocular
      reflex.
AB  - The three pairs of semicircular canals within the labyrinth are not perfectly
      aligned with the pulling directions of the six extraocular muscles. Therefore,
      for a given head movement, the vestibulo-ocular reflex (VOR) depends upon central
      neural mechanisms that couple the canals to the muscles with the appropriate
      functional gains in order to generate a response that rotates the eye the correct
      amount and around the correct axis. A consequence of these neural connections is
      a cross-axis adaptive capability, which can be stimulated experimentally when
      head rotation is around one axis and visual motion about another. From this
      visual-vestibular conflict the brain infers that the slow-phase eye movement is
      rotating around the wrong axis. We explored the capability of human cross-axis
      adaptation, using a short-term training paradigm, to determine if torsional eye
      movements could be elicited by yaw (horizontal) head rotation (where torsion is
      normally inappropriate). We applied yaw sinusoidal head rotation (+/-10 degrees,
      0.33 Hz) and measured eye movement responses in the dark, and before and after
      adaptation. The adaptation paradigm lasted 45-60 min, and consisted of the
      identical head motion, coupled with a moving visual scene that required one of
      several types of eye movements: (1) torsion alone (-Roll); (2)
      horizontal/torsional, head right/CW torsion (Yaw-Roll); (3) horizontal/torsional,
      head right/CCW torsion (Yaw+Roll); (4) horizontal, vertical, torsional combined
      (Yaw+Pitch-Roll); and (5) horizontal and vertical together (Yaw+Pitch). The
      largest and most significant changes in torsional amplitude occurred in the Yaw
      Roll and Yaw+Roll conditions. We conclude that short-term, cross-axis adaptation
      of torsion is possible but constrained by the complexity of the adaptation task:
      smaller torsional components are produced if more than one cross-coupling
      component is required. In contrast, vertical cross-axis components can be easily
      trained to occur with yaw head movements.

PMID- 12520404
TI  - Linearity, symmetry and additivity of the human eye-movement response to
      maintained unilateral and bilateral surface galvanic (DC) vestibular stimulation.
AB  - Recent studies have shown that, although responses to long-duration, constant
      current surface galvanic vestibular stimulation (GVS) show substantial
      interindividual variability, individual subjects show a reliable, repeatable,
      idiosyncratic oculomotor response pattern to GVS. It follows that GVS may be a
      more reliable stimulus than may have been anticipated from the literature. The
      aim of the present study was to examine the metrics of 3D eye-movement responses
      to maintained (120 s), unilateral and bilateral surface GVS. Eye movements were
      measured using computerised video-oculography. Two experiments were conducted:
      Experiment 1 examined whether the normal response is linear over increasing
      levels of current; and Experiment 2 examined (1) whether the normal response to
      surface GVS is symmetrical when comparing stimulated sides, (2) whether the
      normal response to surface GVS is symmetrical when the polarity of the
      stimulating current was reversed, and (3) whether there is additivity in the
      normal response to combinations of unilateral/bilateral surface GVS. Five
      subjects participated in Experiment 1 and eight subjects participated in
      Experiment 2. In both experiments, the onset of stimulation produced
      characteristic eye-movement responses: changes in torsional position with the
      upper pole of both eyes rolling towards the anode and away from the cathode;
      together with horizontal and torsional nystagmus with slow phases towards the
      anode and away from the cathode; and negligible vertical nystagmus. These
      responses reversed direction at stimulus offset. In the fixation condition of
      Experiment 1, the magnitude of ocular torsional position (OTP) and torsional
      nystagmus responses showed a linear relationship over conditions of increasing
      current strength, as did OTP, torsional and horizontal nystagmus responses in
      darkness. The results of Experiment 2 showed that responses to unilateral
      stimulation are symmetrical between stimulated sides, symmetrical between
      stimulating polarities, and additive (with respect to responses to bilateral
      stimulation). The principles derived from these findings, as well as those of
      recent studies, provide a foundation for future work investigating eye-movement
      responses to surface GVS in patients with known types of vestibular dysfunction.

PMID- 12520405
TI  - Excitability of the ipsilateral motor cortex during phasic voluntary hand
      movement.
AB  - We investigated the influence of self-paced, phasic voluntary hand movement on
      the excitability of the ipsilateral motor cortex. Single- and paired-pulse
      transcranial magnetic stimulation (TMS) was applied to the right motor cortex
      triggered by EMG onset of self-paced movements of individual right hand fingers
      at intervals ranging from 13 to 2,000 ms. Motor evoked potentials (MEPs) were
      evaluated in several left arm muscles. Significant suppression of MEP amplitudes
      was observed when TMS was applied between 35 and 70 ms after EMG onset. This
      inhibition was diffuse, affecting "adjacent" muscles (those near the homologous
      muscle in the same extremity) as well as homologous muscles, but more inhibition
      was observed in adjacent and distal muscles than homologous and proximal muscles.
      Significant inhibition of ipsilateral motor cortex was produced by index finger
      movements (both the extensor indicis proprius and the first dorsal interosseus),
      but not by little finger movement (the abductor digiti minimi). Paired-pulse TMS
      (at 2- and 10-ms interstimulus intervals) showed a significant increase in
      intracortical facilitation (ICF) selectively in the homologous muscle when
      triggered by self-paced movement of the opposite hand, but no change was observed
      in intracortical inhibition. When stimulation was triggered by self-paced
      movements, the silent period of the homologous muscle was significantly
      shortened, but the F-wave and compound muscle action potential were unchanged.
      Our findings demonstrate that voluntary hand movement exerts an inhibitory
      influence on a diffuse area of the ipsilateral motor cortex. This inhibitory
      influence is both time and movement dependent. The inhibitory influence is
      nonselective, while the facilitatory influence (enhancing ICF) appears to act
      selectively on the homologous muscles. These effects are most likely mediated by
      a transcallosal pathway.

PMID- 12520406
TI  - Somatosensory evoked magnetic fields following passive movement compared with
      tactile stimulation of the index finger.
AB  - Cortical processing of passive finger movement was assessed
      magnetoencephalographically in 12 healthy volunteers and compared with
      somatosensory evoked magnetic fields (SEF) following tactile stimulation. A new
      device comprising a clamp-like digit holder facilitated bilateral guidance of the
      briskly elevated index finger. Both passive movement and tactile stimulation
      induced activation of the contralateral primary somatosensory (SI) cortex,
      indicated by six SEF deflections with inter-individually rather consistent peak
      latencies of 20-230 ms following proprioceptive and 20-300 ms following tactile
      stimulation. SEF responses to the two stimulus modalities clearly differed with
      regard to peak latencies, amplitudes and orientations of equivalent current
      dipoles (ECDs). The strength and orientation of proprioception-related ECDs
      suggested sequential activation of SI generators, with possible involvement of
      areas 3a and/or 2 at around 20 ms, area 4 at approximate peak latencies of 65 and
      100 ms and area 3b between 150 to 230 ms. Passive movement elicited additional
      activation of cortical regions outside SI, including the bilateral perisylvian
      regions and the contralateral cingulate gyrus at latencies of 40-470 and 150-500
      ms respectively. The study provides new results with respect to the
      spatiotemporal analysis of proprioception-related cortical processing and may
      contribute to a better understanding of the modality-specific organization of the
      human somatosensory cortex.

PMID- 12520407
TI  - Reaching for virtual objects: binocular disparity and the control of prehension.
AB  - Although, in principle, binocular cues provide veridical information about the
      three-dimensional shape of objects, our perception on the basis of these cues is
      distorted systematically. The consequences of these distortions may be less
      serious than they first appear, however, since in everyday life we rarely are
      required to judge the absolute shape, size or distance of objects. An important
      exception to this is in the control of prehension, where veridical information
      about an object to be grasped is required to plan the transport of the hand and
      to select the most appropriate grip. Here we investigate whether binocular cues
      provide accurate depth information for the control of prehension using disparity
      defined, virtual objects and report that whilst binocular disparity can support
      prehensile movements, the kinematic indices, which reflect distance-reached and
      perceived size, show clear biases. These results suggest that accurate metric
      depth information for the control of prehension is not available from binocular
      cues in isolation.

PMID- 12520408
TI  - Effects of inertial load and cervical-spine orientation on a head-tracking task
      in the alert cat.
AB  - Simultaneous video-fluoroscopic and neck muscle EMG data were recorded from one
      cat performing +/-15 degrees sinusoidal (0.25 Hz) head-tracking movements in the
      sagittal plane in a standing body posture with two initial neck orientations and
      four inertial loads. Radio-opaque markers were inserted into the
      anterior/posterior and lateral aspects of the occipital ridge and C(1)-C(7) to
      measure vertebral displacement. Kinematic data were analyzed, and a computer
      model was applied to the data to characterize the limits of movement in the
      cervical spine and to estimate the moment arms of the neck muscles at different
      orientations of head-neck movement. For each initial neck orientation, the cat
      utilized a distinct set of vertebral alignments, relative joint movements, and
      muscle-activation patterns to achieve the same movement outcome. As inertial load
      increased, vertebral alignments and relative joint movements were constant with a
      vertically oriented neck but differed when the neck was more horizontally
      oriented. Different muscle-activation patterns were used to maintain the same
      kinematic pattern with increased inertial loads. Some muscle EMG response gains
      (rectus capitis major and splenius capitis) increased with increasing mass, while
      others (biventer cervicis and occipitoscapularis) demonstrated an initial
      increase and then a plateau. EMG phases were not affected by changing the mass of
      the system but were affected by changing neck orientation. The model predicted
      that muscle moment arms would vary little for the different vertebral alignments,
      suggesting a robust biomechanical system minimally compensates for small changes
      in task geometry.

PMID- 12520410
TI  - After-effects of visuo-manual adaptation to prisms on body posture in normal
      subjects.
AB  - Postural equilibrium is known to be controlled by sensorimotor reflexes and
      automatic control loops but also depends on high-level body representation in
      space, probably implicating the right temporoparietal cortex. Indeed, short-term
      prism adaptation to a 10 degrees rightward visual shift has been shown to reduce
      predominant postural imbalance in patients with right hemisphere damage, as it
      did for neglect symptoms. These effects are likely to be explained by a high
      level effect of prism adaptation on body and space representation, rather than by
      a sensorimotor effect. Cognitive after-effects of prism adaptation to a leftward
      visual shift, suggesting neglect-like symptoms, have also recently been shown in
      normal subjects on line bisection tasks. In the present study, we investigated
      the effect of wedge prism adaptation on postural control in normal subjects. Two
      groups of seven healthy subjects were either adapted to a leftward or a rightward
      visual shift. Results showed that our procedure induced changes in lateral
      postural control in normal subjects. Furthermore, this lateral postural after
      effect was dependent on direction of prism adaptation. Indeed, only adaptation to
      a leftward visual shift induced significant rightward postural bias in normal
      subjects. The rightward postural lateral displacement was negatively correlated
      with the visual vertical. Both transfer and direction specific effect of visuo
      manual adaptation to prisms on postural control suggest that effects of
      adaptation act more on high-level postural control linked to body representation
      in space or at least reveal close interaction between sensorimotor plasticity and
      body representation.

PMID- 12520409
TI  - Activation of brain stem neurons by irritant chemical stimulation of the throat
      assessed by c-fos immunohistochemistry.
AB  - The method of c-fos immunohistochemistry was used to identify the brain stem
      distribution of neurons activated following irritant chemical stimulation of the
      laryngopharyngeal mucosa. In pentobarbital-anesthetized rats, either water
      (control), nicotine (600 mM, 1 ml) or capsaicin (330 microM, 1 ml) was applied to
      the pharynx via a cannula placed posterior to the soft palate. Following nicotine
      and capsaicin, there was a significant increase in fos-like immunoreactivity
      (FLI) compared with controls in the following areas: nucleus of the solitary
      tract from the level of the pyramidal decussation caudally to the level of the
      area postrema rostrally; dorsomedial aspect of trigeminal subnucleus caudalis
      (Vc); and paratrigeminal islands interspersed in the spinal trigeminal tract.
      There was significantly more FLI in Vc and paratrigeminal nuclei following
      capsaicin than following nicotine, while the reverse was true for NTS. In
      addition, there was a significant increase in FLI in area postrema and the
      ventrolateral medullary region dorsal to the lateral reticular nucleus following
      nicotine but not capsaicin. The distributions of FLI in NTS, area postrema, Vc,
      and paratrigeminal nuclei are consistent with prior anatomical tract-tracing
      studies and suggest roles for these brain stem regions in mediating sensory and
      reflex responses to irritant chemical stimulation of the upper respiratory
      mucosa.

PMID- 12520411
TI  - Nicotinamide prevents the long-term effects of perinatal asphyxia on basal
      ganglia monoamine systems in the rat.
AB  - Asphyxia during birth can cause gross brain damage, but also subtle perturbations
      expressed as biochemical or motor deficits with late onset in life. Thus, it has
      been shown that brain dopamine levels can be increased or decreased depending
      upon the severity of the insult, and the region where the levels are determined.
      In this study, perinatal asphyxia was evoked by immersing pup-containing uterus
      horns removed by hysterectomy in a water bath at 37 degrees C for various periods
      of time from 0 to 20 min. After the insult, the pups were delivered, given to
      surrogate mothers, treated with nicotinamide, further observed and finally, 4
      weeks later, killed for monoamine biochemistry of tissue samples taken from
      substantia nigra, neostriatum and nucleus accumbens. The main effect of perinatal
      asphyxia was a decrease in dopamine and metabolite levels in nucleus accumbens,
      and a paradoxical increase in the substantia nigra. Nicotinamide (100 mg/kg i.p.,
      once a day for 3 days, beginning 24 h after the perinatal asphyctic insult)
      prevented the effect of asphyxia in nucleus accumbens. Furthermore, striatal
      dopamine levels were increased by nicotinamide in asphyctic animals. No apparent
      changes were observed in substantia nigra. A prominent unexpected effect of
      perinatal asphyxia alone was on the levels of the metabolite of 5
      hydroxytryptamine, 5-hydroxyindoleacetic acid (5-HIAA), which were increased in
      substantia nigra and decreased in both neostriatum and accumbens. However,
      nicotinamide increased 5-HIAA levels in all regions, which appeared to be related
      to the extent of the asphyctic insult. These results suggest that nicotinamide is
      a useful treatment against the long-term consequences produced by perinatal
      asphyxia on brain monoamine systems, and that there is a therapeutic window
      following the insult, providing a therapeutic opportunity to protect the brain.

PMID- 12520412
TI  - Microstimulation of macaque V1 disrupts target selection: effects of stimulation
      polarity.
AB  - Microstimulation of the intermediate layers of V1 in rhesus monkeys disrupts
      target selection with saccadic eye movements. To study target selection, one
      visual target was presented in the receptive-field location of the stimulated
      neurons and a second target was presented outside this location. Microstimulation
      delivered with the appearance of the two targets decreased the probability that
      the monkey would select the target placed in the receptive-field location when
      intermediate layers of V1 were stimulated. This interference effect was more
      pronounced when anodal-first pulse pairs were used as compared to when cathodal
      first pulse pairs were used. The superior effectiveness of anodal pulses suggests
      that the interference effect is due to activation of axonal terminals residing
      within intermediate V1.

PMID- 12520413
TI  - Processing of temporal information and the basal ganglia: new evidence from fMRI.
AB  - Temporal information processing is a fundamental brain function, which might
      include central timekeeping mechanisms independent of sensory modality.
      Psychopharmacological and patient studies suggest a crucial role of the basal
      ganglia in time estimation. In this study, functional magnetic resonance imaging
      (fMRI) was applied in 15 healthy right-handed male subjects performing an
      auditory time estimation task (duration discrimination of tone pairs in the range
      of 1,000-1,400 ms) and frequency discriminations (tone pairs differing in pitch,
      around 1,000 Hz) as an active control task. Task difficulty was constantly
      modulated by an adaptive algorithm (weighted up-down method) reacting on
      individual performance. Time estimation (vs rest condition) elicited a distinct
      pattern of cerebral activity, including the right medial and both left and right
      dorsolateral prefrontal cortices (DLPFC), thalamus, basal ganglia (caudate
      nucleus and putamen), left anterior cingulate cortex, and superior temporal
      auditory areas. Most activations showed lateralisation to the right hemisphere
      and were similar in the frequency discrimination task. Comparing time and
      frequency tasks, we isolated activation in the right putamen restricted to time
      estimation only. This result supports the notion of central processing of
      temporal information associated with basal ganglia activity. Temporal information
      processing in the brain might thus be a distributed process of interaction
      between modality-dependent sensory cortical function, the putamen (with a timing
      specific function), and additional prefrontal cortical systems related to
      attention and memory. Further investigations are needed to delineate the
      differential contributions of the striatum and other areas to timing.

PMID- 12520414
TI  - Initiation of the human heave linear vestibulo-ocular reflex.
AB  - The linear vestibulo-ocular reflex (LVOR) was studied in eight normal human
      subjects of average age 24+/-5 years. Subjects underwent a sudden heave
      (mediolateral) translation delivered by a pneumatic servo-driven chair with a
      peak acceleration of 0.5 g while viewing earth-fixed targets at 15, 25, 50, and
      200 cm. Stimuli were provided both with targets continuously visible or
      extinguished just prior to motion. Cancellation was tested using chair-fixed
      targets at each viewing distance. Eye movements were recorded using binocular
      magnetic search coils. Head translation was measured using a linear accelerometer
      attached to the upper teeth, to which also was attached a magnetic search coil
      verifying absence of head rotation. Vergence angles achieved by all subjects were
      appropriate to interpupillary distance and target distance. Heave translations
      evoked horizontal ocular rotations in the opposite direction following a brief
      latency. Latency of the LVOR was determined by automated algorithms based on
      identification of times when eye position and head acceleration exceeded three
      standard deviations (SDs) of baseline noise, and was corrected for differing
      transducer delays. Mean LVOR latency was 30+/-16 ms (mean +/- SD), range 12-53
      ms. Slow phase LVOR amplitude was greater for near and less for more distant
      targets, although all observed responses were suboptimal. Measured 100 ms after
      head translation onset, mean response was 20% of ideal for the target at 15 cm,
      22% at 25 cm, 31% at 50 cm, and 53% at 200 cm. Mean latency was significantly
      longer than the previously reported values for both the human angular VOR and the
      monkey LVOR, and had significant inverse correlation with response magnitude. The
      relatively longer latency of the human LVOR than angular VOR may be tailored to
      match human head movement dynamics.

PMID- 12520415
TI  - Effects of inhibition of neuronal nitric oxide synthase on NMDA-induced changes
      in cerebral blood flow and oxygen consumption.
AB  - This study was performed to determine whether neuronal nitric oxide synthase
      (nNOS) is involved in altering regional cerebral blood flow (rCBF) and oxygen
      consumption during N-methyl- D-aspartate (NMDA) receptor stimulation. A
      craniotomy was performed in rats, under isoflurane anesthesia, to expose the
      cerebral cortex. For the control group (n=7), an NMDA patch (10(-3) M) was
      applied to the exposed cortex (ipsilateral cortex, IC) for 10 min before
      determining rCBF and O(2) consumption. The patch was changed every 5 min. To
      block nNOS, 7-nitroindazole (7-NI, 25 mg/kg i.p.) was administered 30 min before
      NMDA application (7-NI group, n=7). The autoradiographic technique was used to
      determine rCBF and regional O(2) consumption was measured using
      cryomicrospectrophotometry. Blood pressure, heart rate, blood gases, and
      hemoglobin were similar between the two groups. In the control group, rCBF (108+/
      32 ml/100 g per min) and O(2) consumption (4.8+/-0.8 ml O(2)/100 g per min) of
      the IC where NMDA was applied were higher than those of the contralateral cortex
      (CC) (78+/-16 ml/100 g per min and 3.1+/-0.4 ml O(2)/100 g per min,
      respectively). Neither rCBF nor O(2) consumption of the IC of the 7-NI group was
      statistically different from that of the CC. However, O(2) consumption of the IC
      of the 7-NI group was lower (3.9+/-1.0 ml O(2)/100 g per min) than that of the IC
      of the control group. Our data demonstrated that a direct cortical application of
      NMDA increased O(2) consumption and rCBF, and that pretreatment with 7-NI not
      only attenuated the effects of NMDA on rCBF but also decreased the O(2)
      consumption during NMDA receptor stimulation.

PMID- 12520416
TI  - Remote effects of self-paced teeth clenching on the excitability of hand motor
      area.
AB  - We studied remote effects of teeth clenching on motor cortical and spinal cord
      excitability using transcranial magnetic stimulation (TMS), brainstem electrical
      stimulation (BES), and ulnar nerve stimulation (F-wave) in eight normal
      volunteers. The TMS, BES, and ulnar nerve stimulation at the wrist were given at
      different intervals (0-200 ms) after the onset of masseter contraction. Surface
      electromyographic responses were recorded from the first dorsal interosseous
      muscle. Responses at different intervals were compared with the response elicited
      when the subject made no teeth clenching (control response). In TMS, conditioned
      responses (during teeth clenching) were significantly larger than the control at
      all intervals. In contrast, in BES and F-waves, conditioned responses were not
      larger than the control at an early phase (intervals shorter than 50 ms), whereas
      they were larger than the control at later intervals (longer than 50 ms). These
      results suggest that facilitation occurs in the hand motor area at the early
      phase of teeth clenching, and spinal facilitation dominates at its late phase.
      This time course of facilitation may indicate that the motor cortex must regulate
      hand muscles finely at the early phase of teeth clenching, and spinal cord may
      stabilize them firmly at the late phase. The excitability changes of the hand
      motor area may be in parallel with that of the masseter motor area which reflects
      the pattern of masseter contraction when the subject activates the masseter
      muscle phasically at the early phase and sustains that contraction at the late
      phase.

PMID- 12520417
TI  - Balance in a rotating artificial gravity environment.
AB  - When subjects stand at the center of a fully enclosed room that is rotating at
      constant velocity, their natural postural sway generates Coriolis forces that
      destabilize their center of mass and head. We quantitatively assessed how
      exposure to constant velocity rotation at 10 rpm affected postural control.
      Twelve subjects stood in a heel-to-toe stance in the rotating room. Each test
      session involved three phases: (1) pre-rotation, (2) per-rotation, and (3) post
      rotation. In each phase, subjects were tested in both eyes open and eyes closed
      conditions. Four measures were used to characterize center of mass movement and
      head movement: mean sway amplitude, total power, mean power frequency, and
      frequency of maximum power. Each measure was computed for anterior-posterior and
      medial-lateral sway. Both anterior-posterior and medial-lateral head and center
      of mass sway during rotation had significantly greater mean sway amplitude and
      total power compared with pre- and post-rotation values. Mean power frequency and
      frequency of maximum power were little affected. Eyes open conditions were
      significantly more stable in all test phases than eyes-closed, but vision did not
      completely suppress the effects of rotation. The greatest effect of rotation was
      in the eyes-closed condition with mean sway amplitude and total power increasing
      more than twofold. Inverted pendulum sway was maintained in all phases of both
      test conditions. No aftereffects of rotation were present after the four 25-s
      exposures each subject received. We expect that with longer exposure periods and
      with active generation of body sway subjects would both adapt to rotation and
      exhibit post-rotary aftereffects.

PMID- 12520419
TI  - The past, present and future of Spanish analytical chemistry.

PMID- 12520420
TI  - The Austrian Society of Analytical Chemistry (ASAC) becomes a supporting partner
      of Analytical and Bioanalytical Chemistry.

PMID- 12520418
TI  - Anticipatory adjustments in the unloading task: is an efference copy necessary
      for learning?
AB  - In the unloading task, a weight is held in the palm of one hand. When an external
      agent removes the weight, an upward perturbation of the loaded hand is observed.
      However, when a person removes the weight by lifting it with their own hand, the
      perturbation is attenuated due to an anticipatory adjustment of the flexor
      muscles in the load-bearing arm. An experiment was conducted to examine
      conditions under which this anticipatory response could be learned. Using a
      virtual reality system with force-feedback robotic arms, normal subjects
      performed the unloading task under one of four learning conditions: (a) the
      participant initiated the unloading by pressing a button, (b) the unloading was
      cued by a brief visual stimulus, (c) the unloading was performed by a virtual
      "hand" that moved smoothly towards the object, and (d) the unloading followed
      three rhythmic force-pulses applied to the finger of the participant. After
      extended practice (192 trials) we found a significant reduction of the upward
      perturbation only in the button pressing condition. Control conditions indicated
      that the acquired response was due to an anticipatory feedforward response rather
      than due to a change in tonic state such as an increase in arm stiffness. These
      results indicate that a voluntary action is necessary to acquire an anticipatory
      adjustment in the unloading task.

PMID- 12520421
TI  - Analytical partnership.

PMID- 12520424
TI  - Diversify, diversify.change is good.and necessary.

PMID- 12520425
TI  - The international patent system, your instrument of revolution.

PMID- 12520426
TI  - Classification of protein microarrays and related techniques.

PMID- 12520427
TI  - Chemometrics for spectroscopic analysis.

PMID- 12520428
TI  - Capillary electromigration separation techniques - current trends.

PMID- 12520430
TI  - Capillary columns in liquid chromatography.

PMID- 12520429
TI  - Computational bioanalysis of proteins.

PMID- 12520432
TI  - Aerosol particle analysis: challenges and progress.

PMID- 12520431
TI  - Single-cell analysis by capillary electrophoresis.

PMID- 12520433
TI  - Miniaturization of electroanalytical systems.

PMID- 12520434
TI  - Real-time mass spectrometry.

PMID- 12520435
TI  - Analytical advances in the SEM.

PMID- 12520436
TI  - Isotope dilution analysis for speciation.

PMID- 12520437
TI  - Environmental immunoassays.

PMID- 12520438
TI  - Analytical characterization of thin carbon films.
AB  - CH(x) films on silicon substrates deposited by a Mesh Hollow Cathode Process
      (MHC) were analyzed by various techniques. The films were produced with varying
      deposition times, resulting in thicknesses ranging from ~2-20 nm. X-Ray
      Reflectivity (XRR) was used to determine the film thicknesses and the deposition
      rate. A good correlation of measured XRR thicknesses with SIMS sputter depths
      down to the film-substrate transition was found. An AFM-based nanoscratching
      technique was applied to test the wear resistance of the thin overcoats. The MHC
      films reveal slightly decreasing scratch resistance for reduced film thicknesses,
      which can be explained by a higher fraction of soft interface zones for thinner
      films. This is in accordance with Raman spectroscopic measurements in the visible
      spectral range which were carried out to examine the carbon bonding properties.
      Combined analysis of G peak position and D/G peak intensity ratio indicates a
      more graphitic structure for film thicknesses less than 10 nm.

PMID- 12520439
TI  - Protein adsorption on surfaces: dynamic contact-angle (DCA) and quartz-crystal
      microbalance (QCM) measurements.
AB  - Adsorption of the protein bovine serum albumin (BSA) on gold has been tested at
      various concentrations in aqueous solution by dynamic contact-angle analysis
      (DCA) and quartz-crystal microbalance (QCM) measurements. With the Wilhelmy plate
      technique advancing and receding contact angles and the corresponding hysteresis
      were measured and correlated with the hydrophilicity and the homogeneity of the
      surface. With electrical admittance measurements of a gold-coated piezoelectrical
      quartz crystal, layer mass and viscoelastic contributions to the resonator's
      frequency shift during adsorption could be separated. A correlation was found
      between the adsorbed mass and the homogeneity and hydrophilicity of the adsorbed
      film.

PMID- 12520440
TI  - A century of progress in the sciences due to atomic weight and isotopic
      composition measurements.
AB  - Even before the 20th century, a consistent set of internationally accepted atomic
      weights was an important objective of the scientific community because of the
      fundamental importance of these values to science, technology and trade. As the
      20th century progressed, physicists, geoscientists, and metrologists collaborated
      with chemists to revolutionize the science of atomic weights. At the beginning of
      the century, atomic weights were determined from mass relationships between
      chemical reactants and products of known stoichiometry. They are now derived from
      the measured isotopic composition of elements and the atomic masses of the
      isotopes. Accuracy in measuring atomic weights has improved continually, leading
      to the revelation of small but significant variations in the isotope abundances
      of many elements in their normal terrestrial occurrences caused by radioactivity
      and a variety of physicochemical and biochemical fractionation mechanisms. This
      atomic-weight variability has now been recognized as providing new scientific
      insights into and knowledge of the history of materials. Atomic weights, except
      those of the monoisotopic elements, are thus no longer regarded as "constants of
      nature". At the beginning of the 20th century, two scales for atomic weights were
      in common use: that based on the atomic weight of hydrogen being 1 and that based
      on the atomic weight of oxygen being 16. Atomic weights are now scaled to (12)C,
      which has the value 12 exactly. Accurate atomic weights of silicon, silver, and
      argon, have enabled the values of the Avogadro, Faraday and Universal Gas
      constants, respectively, to be established, with consequent effects on other
      fundamental constants.

PMID- 12520441
TI  - Coupling solid-phase microextraction to liquid chromatography. A review.
AB  - Solid-phase microextraction (SPME) is a technique for extraction of organic
      compounds from gaseous, aqueous, and solid matrices. SPME is rapid and simple,
      ideal for automation and for in situ measurements, and no harmful solvents are
      needed. The principle of SPME involves equilibration of the analytes between the
      sample matrix and an organic polymeric phase coated on a fused-silica fiber. SPME
      is traditionally combined with analysis by gas chromatography (GC) and this
      combination has proved sensitive, accurate, and precise for quantitative analysis
      of different classes of volatile compound. More recently SPME has been coupled
      with liquid chromatography to widen its range of application to non-volatile and
      thermally unstable compounds also. This article reviews the status of SPME
      coupled with liquid chromatography. It focuses on different applications of the
      technique, e.g. environmental samples, biological fluids, and food samples, to
      show that SPME-HPLC has great potential in the analysis of a wide range of
      compounds in different matrices.

PMID- 12520442
TI  - Modern stationary phases for ion chromatography.
AB  - Due to the better understanding of the processes taking place at the surface of
      the stationary phases, the number of ion-exchange materials for ion
      chromatography (IC) has increased tremendously over recent years. As a result,
      the multitude of commercially available columns today with their different
      selectivities for anion and cation chromatography is almost confusing. Hence, the
      aim of this article is to describe the different principles determining
      selectivity and ion-exchange capacity and to classify the various ion-exchange
      materials accordingly. To ensure a fair comparison of these columns, the
      selectivity differences are illustrated by showing separations of standards
      rather than individual samples.

PMID- 12520443
TI  - Rapid separation of phenylthiohydantoin amino acids: ambient pressure ion
      mobility mass spectrometry (IMMS).
AB  - An electrospray ionization (ESI) ambient pressure ion-mobility spectrometer
      (APIMS) interfaced to an orthogonal reflector time-of-flight mass spectrometer
      (TOFMS) was evaluated for the first time as a detector for the identification of
      phenylthiohydantoin (PTH)-derivatized amino acids, the final products in the
      Edman sequencing process of peptides and proteins. The drift and flight times of
      the twenty common PTH amino acids were characterized by a well-defined 2-D
      mobility/mass spectral pattern. The combination of mobility/mass modes of
      analysis gave rise to a unique trend-line formation for the series of PTH amino
      acids. In addition, each PTH amino acid had a unique reduced mobility constant
      K(o), thus enabling the differentiation of all the amino acid derivatives
      including the PTH-leucine and PTH-isoleucine isomers. More importantly it was
      shown that it was possible to resolve a complete reference mixture of PTH amino
      acids in a single experimental run in less than 1 min. Detection limits for the
      PTH amino acids were found to range from 1.04 to 3.52 ng; indicating that the
      limits of detection were less than 17.0 pmol for all of the PTH amino acids.

PMID- 12520444
TI  - Carbon nanotube array-based biosensor.
AB  - Aligned multi-wall carbon nanotubes (MWNT) grown on platinum substrate are used
      for the development of an amperometric biosensor. The opening and
      functionalization by oxidation of the nanotube array allows for the efficient
      immobilization of the model enzyme, glucose oxidase. The carboxylated open-ends
      of nanotubes are used for the immobilization of the enzymes, while the platinum
      substrate provides the direct transduction platform for signal monitoring. It is
      also shown that carbon nanotubes can play a dual role, both as immobilization
      matrices and as mediators, allowing for the development of a third generation of
      biosensor systems, with good overall analytical characteristics.

PMID- 12520445
TI  - First investigation of an original device dedicated to the determination of
      gaseous mercury in interstitial air in snow.
AB  - The GAMAS (gaseous mercury in interstitial air in snow) instrument developed in
      our laboratory is a new device devoted to sampling and determination of gaseous
      mercury concentration in interstitial air in snow. Sampling probes inserted in
      the snowpack, coupled with a Gardis mercury vapour analyser, provide reliable and
      original data of vertical profiles of both snow temperature and gaseous mercury
      concentration at several depths in a snow mantle. This instrument has been tested
      successfully in Station Nord in Greenland in February-March 2002. A description
      of this instrument, of the sampling area and its setting up is presented with
      precise details. Illustrations of the first investigations are given showing a
      rapid decrease of gaseous mercury concentration simultaneously with depth. A
      concentration of 0.10 ng/m(3) is reached at 120 cm depth. It may be the result of
      fast oxidation processes occurring within the snowpack. Gaseous mercury behaviour
      in the snowpack is a central parameter to elucidate the fate of deposited mercury
      after mercury depletion events in polar regions. With our new device, we have now
      the opportunity to determine this key parameter.

PMID- 12520446
TI  - The reverse auto-compression system: a new type of column for preparative liquid
      chromatography.
AB  - Axial compression of the stationary phase is an easy technique for packing
      preparative liquid chromatography columns. However, the compression piston often
      needs an important external device to move the external jack. A new type of
      column is described which uses an auto-compression system to move the piston and
      compress the packing material. The system is fitted with a new annular injector
      which is known to reduce the peak tailing. The results of the tests demonstrate
      the ease of use of this column, its efficiency and stability.

PMID- 12520447
TI  - Multi-analyte analysis system using an antibody-based biochip.
AB  - A multi-analyte detection system using a unique antibody (Ab) biochip is
      described. The Ab-based biochip, also referred to as the protein biochip, uses a
      sensor array based on a complementary metal oxide silicon (CMOS) integrated
      circuit. The Ab-biochip has a sampling platform of four-by-four microarrays of
      antibodies deposited onto a Nylon membrane substrate. The micro-arrayed
      antibodies can be interrogated simultaneously or sequentially using the biochip
      sensing array detector with the use of a diffractive optical element illuminating
      each antibody spot individually. The usefulness of the Ab biochip is illustrated
      by the measurements of immunoglobulin G (IgG) used as the model analyte system.
      The detection limit for Cy5-labeled IgG molecules was 13 pg.

PMID- 12520448
TI  - A capillary-based amperometric flow immunoassay for 2,4,6-trichlorophenol.
AB  - This paper describes the development of two different capillary-based
      heterogeneous competitive flow immunoassay formats (capillary flow injection
      immunoassay (CFIIA) and capillary sequential injection immunoassay (CSIIA)) for
      the determination of 2,4,6-trichlorophenol (2,4,6-TCP). The assays are based on
      the competition between the analyte and an analyte derivative labelled with the
      enzyme beta-galactosidase, for an anti-TCP antibody, followed by the injection of
      the mixture at equilibrium into a flow stream, where separation between the
      fractions bound and unbound to the antibody is performed in a glass capillary
      containing immobilised protein A. The antibody-tracer fraction retained inside
      the protein A capillary was measured by injection of 4-aminophenyl- beta- D
      galactoside (4-APG), followed by amperometric detection of the enzymatically
      generated 4-aminophenol (4-AP), leading to a negative correlation between the
      signal and the analyte concentration. The two immunoassay formats were compared
      in terms of sensitivity and speed, giving IC(50) values of 1.41+/-0.03 and 1.64+/
      0.07 micro g L(-1), detection limits of 0.2 and 0.4 micro g L(-1), and sample
      throughputs of 6 and 4 h(-1) for the CFIIA and CSIIA system, respectively. The
      influence of different interfering chlorophenolic compounds in the assay was
      minor, with only one exception (i.e. 2,4-dichlorophenol). In addition, different
      water matrices were tested (surface, tap, and rain water), showing that the
      matrix influence was negligible, except for rainwater, which resulted in a 30%
      increase in sensitivity. As a conclusion, the assay is suitable for the fast
      screening of TCP present at low concentration levels in water samples.

PMID- 12520449
TI  - Hydrolysis of proteins with methanesulfonic acid for improved HPLC-ICP-MS
      determination of seleno-methionine in yeast and nuts.
AB  - In this work, the use of methanesulfonic acid for protein hydrolysis is proposed
      for evaluation of Se-methionine in yeast, Brazil nuts, and possibly other
      selenium-rich biological samples. The hydrolysis was carried out by heating the
      sample with 4 mol L(-1) acid at reflux for 8 h. Two chromatographic techniques
      (size-exclusion and ion-pairing) coupled with ICP-MS detection were used to
      compare the release of Se-methionine from proteins by enzymatic (proteinase K,
      protease XIV) and acid hydrolyses. A more efficient liberation of Se-methionine
      was observed by acid hydrolysis. For quantification, the sample extracts were
      introduced onto a C8 Alltima column, and the separation was achieved with a
      mobile phase containing 5 mmol L(-1) hexanesulfonic acid in citrate buffer (pH
      4.5)/methanol (95:5). The results obtained by standard addition showed 816+/-17
      micro g g(-1) and 36.2+/-1.5 micro g g(-1) of selenium in the form of Se
      methionine in yeast and nuts, respectively (65% and 75% of total selenium).

PMID- 12520450
TI  - Simultaneous determination of arsenic(III) and arsenic(V) by flow injection
      inductively coupled plasma-atomic emission spectrometry (ICP-AES) with ultrasonic
      nebulization.
AB  - A dual-column protocol for the sequential determination of As(III) and As(V) is
      described using inductively coupled plasma-atomic emission spectrometry (ICP-AES)
      with ultrasonic nebulization (USN). This procedure employed a 16-way valve
      containing two different homemade mini columns for selective preconcentration of
      As(III) and As(V). One column was filled with Muromac A-1, which selectively
      preconcentrated As(III) at pH 3 after complexation with ammonium pyrrolidine
      dithiocarbamate (APDC, 0.05%). The effluent of the first column was then passed
      through the second column, which was filled with an anion-exchange resin to
      collect As(V). By using 0.6 M sodium hydroxide, both species were eluted
      sequentially and measured by ICP-AES. Enrichment factors of 136 (17 for micro
      column x8 for USN) for As(V) and 160 (20 for micro column x8 for USN) for As(III)
      were achieved with 4 min preconcentration. With the proposed procedure, the
      detection limits were calculated to be 0.7 micro g L(-1) for As(V) and 0.8 micro
      g L(-1) for As(III) based on (3 sigma) blank determination ( N=10). The relative
      standard deviations for 20 micro g L(-1) of As(V) and As(III) were 5.8% and 6.5%,
      respectively. The recovery for spiked water samples was in the range of 85-112%.

PMID- 12520451
TI  - Identification and quantification of metallothionein isoforms and superoxide
      dismutase in spiked liver extracts using HPLC-ESI-MS offline coupling and HPLC
      ICP-MS online coupling.
AB  - A two-dimensional chromatographic method for the characterization of
      metallothionein isoforms (MT) and superoxide dismutase (SOD) in spiked liver
      extracts was developed for the optimization of extraction procedures from liver
      samples. Element-specific detection (ICP-MS) and molecule-specific detection (ESI
      MS) were applied for maximum species information. A special focus was laid on the
      quantitative data evaluation (species stoichiometry, calibration with and without
      matrix, recovery), which is neglected in most MT/SOD publications with hyphenated
      techniques. Linearity, precision (residual standard deviation of calibration
      curves <10%), and detection limits (<0.6 mg L(-1) for MT isoforms and 13 mg L(-1)
      for SOD) prove the suitability of the method for quantification. An alternative
      quantification is proposed for the extension towards other lesser or even unknown
      trace element species, especially the native porcine MT and SOD.

PMID- 12520452
TI  - Enantiomeric purity determination of ketoprofen by capillary electrophoresis:
      development and validation of the method.
AB  - A simple, fast capillary electrophoresis method for determining the total
      ketoprofen content in an oral pharmaceutical formulation is proposed. The
      addition of 75 mM of heptakis(tri- O-methyl)-beta-cyclodextrin to the background
      electrolyte allows the quantitation of the enantiomeric impurity of ( R)-(-)
      ketoprofen contained in the formulation. A relative limit of detection is
      proposed as a measure of the lowest detectable enantiomeric impurity and the
      results show that the method can detect the minor enantiomer at levels as low as
      0.04% in ( S)-(+)-ketoprofen. The chiral method was validated following ICH
      recommendations and the quality parameters obtained show the suitability of the
      proposed method. The analysis of samples examined during the course of a
      stability study under chiral and achiral conditions revealed that the total
      ketoprofen content did not change significantly with time and the enantiomeric
      impurity range was 0.1-0.4%.

PMID- 12520453
TI  - Voltammetric determination of thiodiglycolic acid in urine.
AB  - In urine the level of thiodiglycolic acid (TDGA) is a sensitive indicator of
      exposure of the human organism to some physiologically active or toxic
      substances, gases and vapors. The determination of TDGA by use of a voltammetric
      method based on electroreduction of TDGA in acidic solution at the hanging
      mercury drop electrode has been developed and practically tested. In order to
      eliminate the matrix effect of urine, prior to voltammetric measurement the
      samples are eluted from a small column of PVC powder. The method is simple, low
      cost, rapid and sensitive, appropriate for the needs of occupational medicine.

PMID- 12520454
TI  - A fluorescence-based assay for nanogram quantification of proteins using a
      protein binding ligand.
AB  - Fluorescence emission has been investigated in the context of estimation of
      proteins at nanogram levels. A Schiff base ligand with donor-acceptor
      substituents has been utilized as a fluorescent probe. The potency of this ligand
      is that it possesses the binding sites for both hydrophobic as well as
      hydrophilic groups in the proteins. The fluorescence emission of the probe was
      enhanced in the presence of nanogram levels of protein, which clearly signifies
      that even the least concentration of the protein is sufficient to perturb the
      environment around the probe. We demonstrate here that the fluorescence
      characteristic of the probe can be utilized to estimate even nanogram levels (66
      ng-1 microgram mL(-1)) of protein. The major limitation of the currently
      available standard methods is the range of protein estimation, which terminates
      at microgram level and the interference due to the specificity of the amino
      acids, which vary from proteins to proteins. This fluorescence emission-based
      method is free from interference from any type of buffers, ionic strength of the
      medium and any specific amino acid residue and is a simple, rapid, single-step,
      sensitive method of estimation which can be applied to different classes of
      proteins.

PMID- 12520455
TI  - Sensitive method for the determination of nitrated polycyclic aromatic
      hydrocarbons in the human diet.
AB  - The presence of nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) as
      contaminants in foods is nowadays a legitimate cause of concern, as they are
      reported to be strong direct-acting mutagens and carcinogens that may pose a risk
      to human health. Nevertheless, their concentrations in foods are in the ultra
      trace region. In this study, we present a very sensitive analytical method for
      the determination of this compound class in complex food matrices. Special
      emphasis was put on sample extraction and clean up. Recoveries of 75% could be
      obtained for 1- and 2-nitronaphthalene; for all other compounds investigated the
      recoveries were >/=94%. The determination of the compounds was performed by gas
      chromatography-mass spectrometry. The results show that the use of negative
      chemical ionization (NCI) increases the sensitivity by one order of magnitude in
      comparison to electron impact ionization (EI) (limits of detection 0.07-0.25
      micro g kg(-1) for EI and 0.01-0.02 micro g kg(-1) for NCI). The influence of the
      sample matrix on the sensitivity of the method is demonstrated with extracts of a
      sample from a duplicate diet study. Due to the lack of a certified reference
      material the suitability of the method is demonstrated with pumpkin seed oil that
      was spiked with nitro-PAHs at two different concentration levels.

PMID- 12520456
TI  - Enhanced selectivity and sensitivity for inorganic anions using an ion-pairing
      reagent and sample stacking in capillary zone electrophoresis with direct UV
      detection.
AB  - In this paper, the use of an ion-pairing reagent to improve the separation
      selectivity of inorganic anions in CZE was demonstrated by the addition of
      tetramethylammonium hydroxide (TMAOH) to the electrolyte. The separation of
      inorganic anions (Cl(-), I(-), Br(-), NO(2)(-), NO(3)(-) and SCN(-)) was
      performed using co-electroosmotic flow (EOF) with direct UV detection at 185 nm.
      The parameters affecting the mobility of the tested anions and the EOF such as
      the electrolyte pH and concentration of TMAOH in the electrolyte were examined to
      optimise the separation conditions. In addition, sample-stacking techniques were
      investigated to improve detection sensitivity. Detection sensitivities were
      improved 5-13-fold using electrokinetic sample stacking. The detection limits
      ranged from 1-3 micro mol L(-1). Finally, the proposed method was used for the
      separation of anions in groundwaters.

PMID- 12520457
TI  - Strategies for detection of the ecotoxicological risks of degradation
      metabolites.

PMID- 12520459
TI  - Clinical promise tempered by reality in the delivery of combined chemoradiation
      for common solid tumors.
AB  - Until quite recently, there was no firmly established role for cytotoxic
      chemotherapy in the curative management approach for many of our most common
      malignancies. Systemic therapy was often reserved for recurrent or metastatic
      disease after initial surgery and/or radiotherapy. Today, the treatment of many
      advanced cancer patients involves integration of chemotherapy into the definitive
      treatment strategy. This evolution in therapy is largely a reflection of the
      clinical trials process that has defined clinical benefit for the addition of
      chemotherapy in several settings. This is good news overall. It validates years
      of preclinical experimentation that predicted advantage in combining chemotherapy
      with radiation. Moreover, with a primary objective to increase cancer cure rates,
      we now see confirmatory evidence across a spectrum of recent clinical trials.
      Tempering this good news is the fact that these gains are often quite small. They
      are commonly accompanied by increased toxicity and are generally achieved in good
      performance status patients who may not accurately reflect the broad cancer
      population. In addition, the first generation of positive trials for a particular
      disease site are often accomplished with vastly differing treatment regimens.
      This frequently leaves the general oncologist to query "which specific approach
      is best?" In this article, we briefly trace the evolution of current therapy
      approaches in 2 common human solid tumors, namely cancer of the head and neck and
      non-small-cell cancer of the lung. The focus involves the development of
      chemoradiation strategies in the definitive treatment setting. Clearly, surgery
      plays a critical role in treatment for many patients in these anatomic
      categories. However, we lack randomized trials that directly compare operative
      versus nonoperative treatment approaches and thus have consciously neglected
      review of the surgical series for purposes of this article.

PMID- 12520460
TI  - The mechanism of action of radiosensitization of conventional chemotherapeutic
      agents.
AB  - It is not an exaggeration to state that most of the advances in curing cancer in
      the last decade have come from successful combinations of conventional
      chemotherapeutic agents with radiation therapy. Further improvements in therapy
      will depend on understanding the mechanisms by which chemotherapy improves the
      effectiveness of radiation in model systems and in patients. In this review, we
      discuss the mechanisms of action of the fluoropyrimidines, gemcitabine, and the
      platinums. The fluoropyrimidines (5-fluorouracil and fluorodeoxyuridine) increase
      the effectiveness of radiation chiefly when given before and during radiation.
      Increased radiation sensitivity occurs in cells that progress inappropriately
      into S phase in the presence of drug, suggesting a key role for dysregulation of
      S-phase checkpoints. Gemcitabine may radiosensitize by a similar mechanism,
      although the relative roles of specific DNA repair pathways (such as homologous
      end rejoining) and of apoptosis remain to be determined. For both of these
      categories of drugs, sensitization probably results when cells that are
      progressing inappropriately through S phase misrepair DNA damage inflicted by
      radiation. Thus, loss of the S-phase checkpoint in cancer cells may provide the
      molecular basis for selective killing of tumors compared with normal tissues.
      Cisplatin has multiple effects on cells, such as adduct formation and DNA damage
      repair inhibition, but the mechanism for selectivity against cancer cells
      compared with normal cells is not yet determined. The identification of the
      enzymatic targets for these drugs offers the potential to develop predictive
      assays for response and to develop methods of imaging the progress of therapy.

PMID- 12520461
TI  - Epidermal growth factor family receptors and inhibitors: radiation response
      modulators.
AB  - Growing evidence suggests that epidermal growth factor family receptors (HERs)
      play a significant role in radiation response. EGFR expression levels and
      activation by ligand correlate with radioresistance, and exogenous HER2
      expression alters radiation response. Preclinical studies of anti-EGFR anti-HER2
      antibodies, and kinase inhibitors that inhibit EGFR, both EGFR and HER2, or all 4
      family members show potential for clinical radiosensitization. Early-phase
      clinical trials of the anti-EGFR antibody, C225, prove the combination of C225
      and radiotherapy to be well tolerated and promising. A phase 3 randomized trial
      in head and neck cancer is underway, and clinical investigation of other HER
      inhibitors is in progress. The mechanisms(s) of radiation response modulation by
      HERs appear complex and diverse. Signal transduction initiated by receptor
      activation promotes survival and proliferation after ionizing radiation, and HER
      inhibitors affect cellular responses to ionizing radiation (IR) in diverse ways,
      including inducing apoptosis, cell cycle arrest, and impeding DNA repair. HER
      signaling and inhibition also affect tumor-stroma interactions, particularly
      angiogenesis and endothelial survival after IR. Further investigation of the
      radiation response modulation by EGFR family members and their inhibitors will
      lead to optimization of this promising therapeutic approach.

PMID- 12520462
TI  - Modulation of cell death in the tumor microenvironment.
AB  - The microenvironment of solid human tumors is characterized by heterogeneity in
      oxygenation. Hypoxia arises early in the process of tumor development because
      rapidly proliferating tumor cells outgrow the capacity of the host vasculature.
      Formation of solid tumors thus requires coordination of angiogenesis with
      continued tumor cell proliferation. However, despite such neovascularization,
      hypoxia is persistent and frequently found in tumors at the time of diagnosis.
      Tumors with low oxygenation have a poor prognosis, and strong evidence suggests
      this is because of the effects of hypoxia on malignant progression, angiogenesis,
      metastasis, and therapy resistance. The presence of viable hypoxic cells is
      likely a reflection of the development of hypoxia tolerance resulting from
      modulation of cell death in the microenvironment. This acquired feature has been
      explained on the basis of clonal selection-the hypoxic microenvironment selects
      cells capable of surviving in the absence of normal oxygen availability. However,
      the persistence and frequency of hypoxia in solid tumors raises a second
      potential explanation. We suggest that stable microregions of hypoxia may play a
      positive role in tumor growth. Although hypoxia inhibits cell proliferation and
      in tumor cells will eventually induce cell death, hypoxia also provides
      angiogenic and metastatic signals. The development of hypoxia tolerance will thus
      allow prolonged survival in the absence of oxygen and generation of a persistent
      angiogenic signal. We will discuss the concept of hypoxia tolerance and review
      mechanisms used by cancer cells to acquire this phenotype. The concept of hypoxia
      tolerance has important implications for current and future therapeutic
      approaches. Most therapeutic efforts to combat hypoxia have focused on targeting
      the presence of hypoxia itself. Our hypothesis predicts that targeting the
      biological responses to hypoxia and the pathways leading to hypoxia tolerance may
      also be attractive therapeutic strategies.

PMID- 12520464
TI  - Targeting the tumor blood vessel network to enhance the efficacy of radiation
      therapy.
AB  - It has been well established that the vascularization of solid tumors is a
      prerequisite if a clinically relevant size is to be reached. For progressive
      tumor growth, the vessel network must continuously expand to satisfy the
      neoplastic cells' nutritional needs and waste product removal requirements. This
      utter reliance of the tumor on its vasculature provides a logical target for new
      approaches to cancer therapy. Indeed, there currently exists a great deal of
      enthusiasm for the development of interventions that compromise the growth and/or
      function of the tumor neovasculature. Two primary directions are being pursued.
      Inhibitors of angiogenesis seek to interrupt the angiogenic process to prevent
      new vessel formation. Antivascular approaches aim to cause direct damage to the
      tumor endothelium and thus lead to extensive secondary neoplastic cell death. The
      application of such strategies as adjuvants to conventional radiation treatments
      offers unique opportunities to develop more effective cancer therapies.

PMID- 12520463
TI  - Combining bioreductive drugs and radiation for the treatment of solid tumors.
AB  - Methods now exist for the identification of human tumors that contain significant
      numbers of hypoxic cells and are thereby suitable for treatment with bioreductive
      drugs to eliminate this refractory cell population. However, to fully exploit the
      potential of bioreductive drugs, they will need to be used in combination with
      other modalities likely to target the proliferating aerobic cells in the tumor.
      Radiation is the treatment that is most effective in killing aerobic cells;
      therefore, the present report reviews the available preclinical data on combined
      radiation/bioreductive drug treatments.

PMID- 12520465
TI  - Chemical radioprotection: a critical review of amifostine as a cytoprotector in
      radiotherapy.
AB  - The use of chemical radioprotectors represents an obvious strategy to improve the
      therapeutic index in radiotherapy. Amofostine (WR-2721) has recently been
      approved for use in head and neck cancer to protect against radiation-induced
      xerostomia. Currently, the question has arisen whether amifostine could be used
      for radioprotection in broader terms. Amifostine may have the potential to enable
      intensified treatment by ameliorating mucosal reactions that are often a limiting
      factor in accelerated fractionation or concomitant chemoradiation. However, it
      has as yet not been clarified whether sufficient amifostine to reduce mucositis
      can be administered before each radiation fraction without causing unacceptable
      toxicity. Also, the optimal dosage and schedule of amifostine in chemoradiation
      combinations have not yet been established. The major concern related to
      radioprotectiors is the potential hazard of collateral tumor protection. A number
      of clinical studies have concluded that amifostine does not reduce antitumor
      efficacy. However, not even the largest study conducted, with over 300 patients,
      has sufficient statistical power to detect a clinically significant reduction in
      tumor control rate. To put this issue ultimately to a rest, a clinical trial with
      a sufficient accrual to definitely rule out a tumor protective effect of
      amifostine needs to be conducted. Substances reducing radiation-induced toxicity
      by modulating the biological response to radiation injury may represent an
      alternative concept in radioprotection. However, such agents are still at a
      developmental stage.

PMID- 12520466
TI  - Pharmacological intervention to prevent or ameliorate chronic radiation injuries.
AB  - Until the 1990s, chronic radiation-induced normal-tissue injury was viewed as
      being due solely to the delayed mitotic death of parenchymal or vascular cells;
      these injuries were held to be inevitable, progressive, and untreatable. It is
      now clear that parenchymal and vascular cells are active participants in the
      response to radiation injury rather than passive observers dying as they attempt
      to divide. This offers fundamentally new approaches to radiation injury because
      it allows for the possibility of pharmacological interventions directed at
      modulating steps in the cascade of events leading to expression of injury. Such
      interventions would be relevant to both cancer patients and victims of radiation
      accidents. Prophylaxis and treatment of chronic radiation injuries have been
      experimentally shown in multiple organ systems (eg, lung, kidney, soft tissue)
      and with fundamentally different pharmacological agents (eg, corticosteroids,
      angiotensin-converting enzyme inhibitors, pentoxifylline, superoxide dismutase).
      For the most part, this has been achieved using clinically relevant radiation and
      drug schedules and with agents that have already been approved for human use.
      Unfortunately, assessment of the utility of these agents for clinical use has
      been minimal, and there are no established mechanisms for any of the experimental
      or clinical successes. Clinical development of pharmacological approaches to
      modification of chronic radiation injuries could lead to significant improvement
      in survival and quality of life for radiotherapy patients and for victims of
      radiation accidents or nuclear terrorism.

PMID- 12520468
TI  - The embryology of the foregut.
AB  - Until today, several theories have been developed to explain the occurrence of
      common foregut malformations as esophageal atresia and tracheoseophageal fistula.
      Most researchers believe that these malformations are the result of an impaired
      process of septation of the early foregut. However, a detailed review of the
      literature makes clear that a unified embryologic concept of the normal foregut
      development is still missing. This statement is still true after the development
      of an animal model, the so-called Adriamycin model in rats, which allows the
      reproduction of embryos, fetuses, and newborns with a huge spectrum of
      malformations, including foregut malformations. In the first part of this review,
      data from the literature are presented and analyzed critically, which deal with
      the differentiation of the foregut into the esophagus and the respiratory tract.
      In general, it is a shortcoming that reliable illustrations of these crucial
      embryologic processes still are missing in most of these reports. Therefore, in
      the second part, scanning electron microscopy pictures of the developing foregut
      are presented in a series of chicken embryos. In these pictures, signs of a
      septum are completely missing as an important structure during the
      differentiation of the foregut. In the third part, the spectrum of theories that
      should explain abnormal foregut malformations is presented and critically
      discussed. In the last section, the Adriamycin model and its implications for the
      current understanding of the foregut malformations is discussed.

PMID- 12520469
TI  - Management of congenital lung lesions.
AB  - The prenatal diagnostic hallmarks, natural history, and management of congenital
      cystic adenomatoid malformation of the lung and pulmonary sequestration are
      reviewed. Large lung tumors may disappear partially on serial prenatal
      sonography, suggesting that improvement can occur occasionally during fetal life.
      The fetus with a lung mass but without hydrops has an excellent chance for
      survival with maternal transport, planned delivery, and postnatal evaluation and
      surgery. The finding that fetuses with hydrops are at very high risk for fetal or
      neonatal death has led to successful fetal thoracoamniotic shunt placement or
      fetal surgical resection.

PMID- 12520470
TI  - New concepts in the pathology of congenital lung malformations.
AB  - Focal developmental malformations of the lung are a heterogeneous group of
      lesions that display a variety of features. They often are thought to be quite
      distinct entities, but there is considerable overlap among these lesions. Both
      standard nomenclature and common usage do not identify clearly the components of
      these lesions in a distinctive fashion. A classification based on pathologic
      features is presented. A malformation sequence based on airway obstruction during
      development is proposed as a unifying pathogenetic mechanism for some seemingly
      unrelated lesions.

PMID- 12520471
TI  - Central hypoventilation and diaphragmatic eventration: diagnosis and management.
AB  - Congenital central alveolar hypoventilation syndrome (CCAHS) is a disorder of
      ventilatory control that occurs without neuromuscular blockade or pulmonary
      disease. It is characterized by a lack of response to habitual respiratory
      stimulants, especially hypercapnia. In this article, the management of this
      syndrome by diaphragmatic pacing is discussed. Paralysis of the phrenic nerve in
      small children usually results from injury during birth or during a
      cardiothoracic operation and results in eventration of the hemidiaphragm.
      Alternatively, eventration of the diaphragm may be a congenital condition. In
      both cases it may lead to respiratory distress in the newborn. In this article,
      we review the diagnosis of these conditions and their management, focusing on the
      surgical indications. We also discuss outcome.

PMID- 12520472
TI  - Diagnosis and treatment of foregut duplications.
AB  - In its broadest sense, the term, foregut duplication encompasses the full
      spectrum of developmental aberrations of the embryonic foregut (bronchopulmonary
      and alimentary tract). Evidence is emerging that the notochord may have a pivotal
      role to play in foregut development through the Shh-GLi signalling pathway. The
      investigation and management of these lesions depends on the clinical
      presentation and the level of the foregut affected. The presentation of
      symptomatic foregut duplications also depends on any space-occupying effect they
      exert and where specific complications related to the malformation occur, such as
      when the mucosal lining contains acid-secreting cells. In a minority of cases,
      (eg, where they cause respiratory compromise or spinal cord compression) urgent
      intervention is required. In the remainder, precise diagnostic imaging according
      to the level and location of the foregut duplication provides the necessary
      information to plan surgical excision of the lesions. Magnetic resonance imaging
      best shows the relationships of complex bronchopulmonary foregut malformations
      and associated anomalies of the spine. eg, neurenteric canal. Most lesions can be
      excised with minimal morbidity. Minimal-access surgical techniques can be applied
      to the simpler cysts, particularly some bronchogenic cysts. Thoraco-abdominal
      duplications and neurenteric cysts require careful preoperative delineation and
      more complex surgery.

PMID- 12520473
TI  - Pediatric spontaneous pneumothorax.
AB  - The aim of this study was to review pediatric spontaneous pneumothorax and
      describe diagnostic and therapeutic approaches and to review our institutional
      experience with spontaneous pneumothorax. A medline search using keywords
      pneumothorax and pediatric in both French and English from 1988 through May 2002
      was performed, and pertinent papers regarding the natural history, diagnosis,
      imaging, and therapy were reviewed. A 10-year chart review of spontaneous
      pneumothorax recording data on demographics, diagnostic imaging, therapeutic
      approach, and outcomes was performed. Only 4 case series and one review article
      were produced by the medline search involving exclusively pediatric spontaneous
      pneumothrax. One hundred ninety-six other articles involved adult series with a
      minority of patients under 18 years of age. A subset of articles from this adult
      based group were examined to assist in formulating recommendations for diagnosis,
      imaging, treatment, and surgical management of pediatric spontaneous
      pneumothorax. Few articles on this topic report randomized studies in the adult
      literature and none in the pediatric literature. The chart review yielded 53
      cases of spontaneous pneumothorax in 40 patients with important data presented in
      the current review. Although few articles are able to provide best-evidence
      information, the diagnosis, imaging, treatment, and surgical management of
      patients with primary spontaneous pneumothorax is achieved with good results.
      Stronger data specific to pediatric patients are needed.

PMID- 12520474
TI  - The role of thoracoscopy in pediatric surgical practice.
AB  - Originally described in the early 20th century, the technique of thoracoscopy was
      first applied to children in the mid 1970s. Since that time, the technique has
      become adopted widely by pediatric surgeons and is currently considered to be the
      optimum technique for management of many intrathoracic disorders in children. In
      most pediatric surgical practices, the most common indications for thoracoscopy
      include pleural debridement for empyema, mediastinal lymph node biopsy, and
      pulmonary parenchymal biopsy for inflammatory infiltrates or nodules. With proper
      adherence to patient selection and preoperative imaging as well as appropriate
      anesthetic techniques, this procedure has proven to be extremely accurate in
      achieving a diagnosis and very successful in treating most patients.
      Postoperative recovery is rapid, and complications of the procedure have been
      relatively infrequent. As pediatric surgeons gain more experience with this
      technique and as better instrumentation becomes available, thoracoscopy surely
      will be used for an increasing number of complex intrathoracic disorders.

PMID- 12520475
TI  - Endoscopic management of tracheal and esophageal strictures.
AB  - The management of a pediatric patient with a severe tracheoesophageal stricture
      may be the most frustrating and enduring experience encountered by the pediatric
      general surgeon; yet, when successful, it is one of the most rewarding. Adopting
      a multidisciplinary approach to these problems offers the greatest chance for
      success. Endoscopic management of such cases at times seems the most reasonable
      choice. With advances in pediatric anesthesia, endoscopic equipment, and stent
      technology, currently these procedures can be performed safely and offer a viable
      alternative to the more invasive conventional redo operations. A review of
      available, yet, by no means, all-inclusive endoscopic options with an emphasis on
      stent technology is presented using select case illustrations.

PMID- 12520477
TI  - Diagnosis of multiple myeloma.
AB  - Appropriate diagnosis of multiple myeloma is critical for proper initial therapy.
      This article describes the criteria necessary for the diagnosis of multiple
      myeloma and differentiates multiple myeloma from smoldering multiple myeloma,
      monoclonal gammopathy of undetermined significance, other metastatic cancers, and
      amyloidosis.

PMID- 12520478
TI  - Myeloma and the newly diagnosed patient: a focus on treatment and management.
AB  - An evidence-based approach to the management of newly diagnosed multiple myeloma,
      developed at the Mayo Clinic (Rochester, MN), is summarized in this article. The
      optimum pretransplant induction regimen for multiple myeloma is described, and
      outcomes for early and delayed transplantation, one versus two transplants, the
      role of thalidomide in smoldering multiple myeloma, and the role of maintenance
      therapy are discussed. The role of supportive care strategies for patients with
      bone disease, such as the use of bisphosphonates, is also discussed.

PMID- 12520480
TI  - Moving disease biology from the laboratory to the clinic.
AB  - To address the urgent need for novel therapies for multiple myeloma (MM), long
      term research efforts have characterized the mechanisms whereby MM cells home to
      the bone marrow and adhere to bone marrow stromal cells and extracellular matrix
      proteins. Research also characterizes the functional sequelae of this binding to
      identify targets for novel therapies. This article describes the mechanisms by
      which MM cells home to bone marrow and adhere to bone marrow stromal cells and
      extracellular matrix proteins, and describes the functional sequelae of this
      binding. Adhesion molecules that mediate MM cell binding to bone marrow stromal
      cells are identified, and the growth and survival advantage conferred by this
      binding is discussed. The biologic significance of cytokines in MM pathogenesis
      and the signaling cascades mediating their effects are delineated. Apoptotic and
      targeted therapeutic strategies to overcome drug resistance based on interrupting
      growth or triggering apoptotic-signaling cascades also are identified, providing
      the basis for novel biologically based therapies, such as
      thalidomide/immunomodulatory drugs and proteasome inhibitor PS-341.

PMID- 12520479
TI  - Advances in the biology and treatment of myeloma bone disease.
AB  - The major clinical manifestations of multiple myeloma are related to the loss of
      bone. This bone loss often leads to pathologic fractures, spinal cord
      compression, hypercalcemia, and bone pain. This article reviews the cytokine
      network involved in myeloma bone disease; describes the signaling cascade
      involved in osteoclastogenesis and mechanisms of action of novel therapeutic
      options for myeloma bone disease such as osteoprotegerin, RANK human
      immunoglobulin fusion protein, the proteasome inhibitor PS-341, and
      bisphosphonates; and summarizes the latest clinical trial results using oral and
      intravenous bisphosphonates for bone disease in multiple myeloma.

PMID- 12520481
TI  - Drug resistance and drug development in multiple myeloma.
AB  - Circumvention of drug resistance in multiple myeloma is a major obstacle to
      improving clinical outcomes for myeloma patients. Identification of several
      mechanisms of acquired drug resistance has led to the development of
      chemosensitizing agents that counter specific drug resistance mechanisms. Initial
      successes in therapy using chemosensitizers often culminate in relapse because of
      the multifactorial nature of acquired multidrug resistance. Therefore, it may be
      important to design therapeutic strategies that focus on mechanisms that allow
      for cell survival following initial treatments, before the acquisition of
      multidrug resistance. It has been proposed that extracellular effectors such as
      cytokines, matrix components, and adjacent cells may provide a sanctuary for
      cancer cells by preventing stress-induced cell death. This review focuses on
      research implicating the cancer cell environment as a particularly important
      determinant in the emergence of drug resistance.

PMID- 12520482
TI  - High-dose therapy and immunomodulatory drugs in multiple myeloma.
AB  - The principle of alkylating agent dose intensity, especially with melphalan-based
      tandem autotransplants, has been effective in increasing the rate of complete
      remission beyond 40% and effecting 10-year survivorship in about 40% of the three
      fourths of patients presenting without cytogenetic abnormalities (Total Therapy
      I). Further dose escalation and post-transplant consolidation therapy, as
      practiced with Total Therapy II, seems to further improve results in these
      patients, but not in those with chromosome 13 abnormalities or lactate
      dehydrogenase elevation. Phase III trials for post-transplant relapse indicate
      higher complete remission and near-complete remission rates among patients
      randomized to thalidomide added to dexamethasone versus dexamethasone alone. In a
      phase I/II study, thalidomide derivative CC-5013, with less sedative and
      neurotoxic effects, promoted responses in eight of 15 patients with post
      transplant relapse, refractory to other salvage therapies, at dose levels of > or
      = 25 mg daily. Based on a profound graft-vs-myeloma effect with allografts, mini
      allotransplants were evaluated in 31 high-risk patients with cytogenetic
      abnormalities and prior autotransplants; all nine with responsive disease and
      only one prior autotransplant remain disease-free and alive. Such mini
      allotransplants are now offered as consolidation after one standard
      autotransplant to patients with cytogenetic abnormalities. The systematic
      application of gene expression profiling attempts to classify multiple myeloma
      (MM) patients according to molecular features and to dissect the genetic basis
      for drug sensitivity or resistance. Given the availability of an expanding
      treatment armamentarium (eg, thalidomide, CC-5013, the proteasome inhibitor PS
      341, farnesyltransferase inhibitors, IL-6 receptor antibody, endothelial receptor
      inhibitor), gene expression profiling is anticipated to help in the selection of
      agents with the greatest probability of activity toward individualized treatment.
      Careful scrutiny of gene expression will also help in the identification of
      unrecognized targets for therapeutic intervention.

PMID- 12520483
TI  - Low-dose thalidomide in myeloma: efficacy and biologic significance.
AB  - The efficacy of thalidomide at doses as low as 50 mg every other day was first
      reported at the VII International Multiple Myeloma Workshop in Stockholm, Sweden,
      in September 1999. This article discusses the duration of responses with low-dose
      thalidomide and the subsequent efficacy with thalidomide combination approaches.
      The median effective dose of thalidomide was 200 mg/d. Thalidomide's mechanism of
      action, particularly its effects on macrophages, is described. Current approaches
      to single-agent and combination therapy are presented.

PMID- 12520484
TI  - Use of an active intra-abdominal drain in 67 horses.
AB  - OBJECTIVE: To describe the insertion technique, efficacy, and complications
      associated with the use of an active (closed-suction) abdominal drain in horses.
      STUDY DESIGN: Retrospective study. Animals-Sixty-seven horses with abdominal
      contamination treated by abdominal lavage and use of a closed-suction abdominal
      drain. METHODS: Medical records of horses (1989-1996) that had a closed-suction
      abdominal drain were reviewed. Follow-up information was obtained by telephone
      interviews with owners. RESULTS: Sixty-eight closed-suction abdominal drains were
      used in 67 horses that had abdominal contamination, peritonitis, or to prevent
      adhesion formation. The drain was placed under general anesthesia (62 horses) or
      in a standing position (6 horses). Abdominal lavage was performed every 4 to 12
      hours and about 83% of the peritoneal lavage solution was retrieved. Minor
      complications associated with drain use occurred in 49% of the horses and
      included obstruction or slow passage of fluid through the drain in 18 horses
      (26%), leakage of fluid around the drain in 11 horses (16%), and subcutaneous
      fluid accumulation around the drain in 8 horses (12%). Incisional suppuration
      developed in 20 of 62 (32%) and incisional herniation in 5 of 46 (11%) horses.
      CONCLUSIONS: A closed-suction drain system was easily placed and was associated
      with only minor complications in most horses. CLINICAL RELEVANCE: Active
      abdominal drainage and lavage is a useful adjunct in the treatment of peritonitis
      or as a prophylactic procedure in horses at risk of developing septic peritonitis
      and abdominal adhesions. Clinicians should be aware of the high incidence of
      minor complications.

PMID- 12520485
TI  - Use of veterinary interlocking nails for diaphyseal fractures in dogs and cats:
      121 cases.
AB  - OBJECTIVE: To report clinical outcome after use of an interlocking nail
      (veterinary interlocking nail [VIN]) for stabilization of diaphyseal fractures in
      dogs and cats. STUDY DESIGN: Retrospective study. ANIMALS: Seventy-eight dogs and
      43 cats with diaphyseal fractures of the femur (n = 96), tibia (n = 14), or
      humerus (n = 11). METHODS: Interlocking nails (4 mm diameter [n = 72], 6 mm [n =
      25] or 8 mm [n = 24]), were used in static (n = 106) or dynamic (n = 15) fixation
      mode. Cerclage wires also were used in 63 (52%) cases. Data about the patient
      (species, breed, weight, age), characteristics of the fracture, and details of
      the surgery and perioperative complications were recorded. The surgeon evaluated
      functional outcome, and fracture healing was quantified 6 weeks (W6) and 3 months
      (M3) after surgery with a radiographic index. RESULTS: Twelve cases had been
      unsuccessfully treated by another technique. Of 106 comminuted fractures, 60 were
      classified as unstable. Only 112 animals were evaluated at W6; 86 (77%) healed
      without complication and had a functional outcome considered excellent (n = 80,
      93%), good (n = 5, 4%), or fair (n = 1). Twenty-six complications were noted: 16
      (14%) patients did not require additional surgery and had a good or excellent
      outcome, whereas 10 (8%) patients needed surgical intervention to CONCLUSIONS:
      VINs can be used to repair diaphyseal fractures of the femur, tibia, and humerus
      in dogs and cats provided the implants are appropriately sized for the fractured
      bone. The high healing rate (even with unstable fractures), associated with a
      functional outcome, and low complication rate support the use of VINs for these
      fracture types. However, a period of training and the application of basic
      principles are necessary to ensure successful results. CLINICAL RELEVANCE: VINs
      should be considered as alternative technique for management of selected
      diaphyseal fractures of the femur, tibia, and humerus in dogs and cats.

PMID- 12520487
TI  - Repair of femoral capital physeal fractures in 12 cattle.
AB  - OBJECTIVE: To document signalment, clinical signs, and long-term outcome of
      surgical treatment for femoral capital physeal fractures in cattle. STUDY DESIGN:
      Retrospective study. Animals-Twelve cattle with femoral capital physeal
      fractures. METHODS: Cases were identified by a search of radiographic records.
      Historical, diagnostic, surgical, and outcome data were collected from the
      medical records. Owners were contacted for follow-up information by telephone.
      RESULTS: Fractures were repaired by screws inserted in lag fashion in 4 animals
      and by use of multiple intramedullary pins in 8 animals. Six of 12 animals
      required repeat surgery to reposition screws or pins. Nine animals were
      considered successfully treated at discharge. Six months after surgery, 6 of 11
      animals for which follow-up was obtained were still sound. At 12 months, 4 of 4
      animals alive were still sound. Animals that bore weight earliest postoperatively
      were more likely to have a successful outcome. Animals <12 months of age had
      better outcomes than animals >12 months of age. CONCLUSIONS: Prognosis for
      serviceable soundness is good in cattle <12 months of age and fair in animals >12
      months of age after surgical repair of femoral capital physeal fracture by
      stacking intramedullary pins or by screws inserted in lag fashion. CLINICAL
      RELEVANCE: Surgical repair of femoral capital physeal fracture is most successful
      in younger cattle and can result in productive animals.

PMID- 12520486
TI  - Lumbosacral stenosis in 29 military working dogs: epidemiologic findings and
      outcome after surgical intervention (1990-1999).
AB  - OBJECTIVE: To study the outcome of military working dogs (MWDs) diagnosed with
      degenerative lumbosacral stenosis (DLS) after surgical intervention and to
      determine what prognostic indicators affected outcome. STUDY DESIGN:
      Retrospective study. ANIMALS: Twenty-nine MWDs with DLS. METHODS: The medical
      records of dogs diagnosed and surgically treated for DLS at the Department of
      Defense Military Working Dog Veterinary Service Hospital were reviewed. Retrieved
      data were signalment, clinical signs, survey radiograph results, and surgical
      findings. RESULTS: Breed and sex were not found to have prognostic significance.
      Increasing age at surgery correlated with a poor surgical outcome. Twelve dogs
      (41%) returned to normal function, 11 (38%) improved, and 6 (20%) never returned
      to active duty. The average age at surgery was 74 months, 93 months, and 112
      months for normal, improved, and dogs not returning to duty, respectively.
      Significant clinical findings associated with a poor prognosis were related to
      increasing neurologic severity. The only significant radiographic finding
      indicating a poor prognosis was foraminal narrowing. Surgical findings with
      negative prognostic significance were hypertrophic articular facets and
      interarcuate ligament. Recurrence rates were 16.7% and 54.5% for normal and
      improved dogs, respectively. CONCLUSIONS: MWDs with DLS have a good prognosis
      with surgical decompression if they are young dogs with mild clinical signs at
      the time of diagnosis. As age and severity of clinical signs increase, the
      prognosis for successful outcome decreases. Recurrence may be seen in some dogs.
      CLINICAL RELEVANCE: Information provided by this study should help military
      veterinarians determine the prognosis for working dogs with DLS after surgical
      treatment.

PMID- 12520488
TI  - The effects of femoral stem and neck length on cement strains in a canine total
      hip replacement model.
AB  - OBJECTIVE: To determine the effects of femoral prosthesis stem length and head
      size on cement strains in a canine hip replacement system. STUDY DESIGN: An in
      vitro experimental model. SAMPLE POPULATION: (1) Three standard and 3 1-cm
      shortened femoral implants with +3 femoral heads. (2) Two standard implants with
      +0, +3, and +6 femoral heads. METHODS: Femoral stems were embedded in
      polymethylmethacrylate cement. A uniaxial proximodistal-oriented strain gauge was
      applied to the cement on the medial and lateral aspects of the construct 1.5 cm,
      6.0 cm and 7.0 cm distal to the collar. Each construct with a +3 femoral head was
      mounted in a materials testing system. An axial compressive load (0-200 N) was
      applied to the femoral head and cement strains were recorded. Additionally, 2
      standard length constructs were also tested with +0 and +6 femoral heads. The
      effects of stem length and neck length on cement strains were assessed with
      analysis of variance. RESULTS: Strains increased at all locations with increasing
      loads for all constructs. Shorter implants had higher strains by 152% and 171%,
      lateral (P =.003) and medial (P =.0025) to the stem tip. No significant strain
      differences were noted, at any strain gauge location, between different neck
      lengths (P values ranged from.20 to.67). CONCLUSIONS: Although a shorter implant
      stem has a potential to improve implant fit, it led to significantly higher
      cement strains that may increase the risk for aseptic loosening. Changes in
      femoral neck length did not significantly affect cement strains under the
      conditions tested. CLINICAL RELEVANCE: Shortening of the femoral stem currently
      cannot be recommended in canine total hip replacement. The existing use of
      variable neck lengths likely does not increase the risk of failure of the femoral
      stem.

PMID- 12520489
TI  - Reduction and stabilization of hip luxation by the transposition of the
      ligamentum sacrotuberale in dogs: an in vivo study.
AB  - OBJECTIVES: To evaluate the effectiveness of transposition of the sacrotuberous
      ligament (LST) for the treatment of coxofemoral luxation in the dog. STUDY
      DESIGN: In vivo experimental study. SAMPLE POPULATION: Ten mixed-breed dogs
      (weighing 12 to 26 kg). METHODS: After general anesthesia, the LST was exposed
      and released from the sacrum with a sacral bone fragment. Coxofemoral luxation
      was created by capsulotomy and transection of the ligament of the head of the
      femur. Suture was passed through 2 small holes in the bone fragment to guide
      transposition of the LST through a tunnel drilled through the acetabulum and
      femoral head and neck. The suture material was pulled tight and an interference
      screw was placed into the femoral tunnel to lock the sacral bone fragment and LST
      securely in the tunnel. Butorphanol was administered for pain relief and dogs
      were allowed unrestricted activity. Coxofemoral radiographs were obtained at 15
      day intervals. Two dogs were euthanatized for macroscopic and histopathologic
      examinations at 3 months. RESULTS: Release of the sacral bone was moderately
      difficult. The transposed ligament and bone fragment were of an appropriate
      length and were easily and securely fixed by a interference screw method. Visible
      severe lameness, during the first 7 to 10 days improved to mild lameness within
      10 to 21 days. Gait was subjectively normal after 5 weeks. No radiographic
      abnormalities were observed at any time point. Grossly, the LST was intact and
      apparently viable and functional. On histopathology, the space in the bone tunnel
      was filled with new tissue and a hyaline-like layer surrounded the LST. The
      sacral bone fragment attached to the LST was united with the femoral bone.
      CONCLUSIONS: Transposition of the LST reduced and stabilized experimentally
      induced coxofemoral luxation in 10 dogs. Survival of the LST up to 3 months and
      its adaptation to transposition suggest that this surgical technique could be
      considered as a permanent treatment option for hip luxations. Transposition and
      fixation of the LST was easy, but releasing the sacral edge of the LST was
      difficult because of its deep location and division of the origin into 2 branches
      in some dogs. CLINICAL RELEVANCE: Results of this experimental study suggest that
      the technique may be satisfactorily used in dogs with coxofemoral luxation.

PMID- 12520490
TI  - Use of an isolated intestinal circuit to evaluate the effect of ischemia and
      reperfusion on mucosal permeability of the equine jejunum.
AB  - OBJECTIVES: To evaluate the efficacy of an isolated perfusion circuit and the
      effect of ischemia-reperfusion on mucosal permeability of the jejunum. STUDY
      DESIGN: In vitro study of intestinal mucosal permeability. ANIMALS: Twelve
      healthy adult horses. METHODS: A control segment of jejunum was placed in an
      isolated perfusion circuit for 240 minutes and mucosal permeability was measured.
      After detecting no deleterious effects of the isolated system on the control
      intestine, low flow ischemia was created in experimental segments for 20, 40, 60
      and 90 minutes followed by 60 minutes of reperfusion and mucosal permeability was
      evaluated. At the completion of the studies, histologic evaluation was used to
      determine mucosal grades, surface area, and volume. RESULTS: Control tissue was
      maintained in the isolated circuit for 240 minutes without effect on mucosal
      grade, surface area, or volume relative to intact tissue. After ischemia
      reperfusion, mucosal grade increased, and volume and surface area decreased
      progressively with longer periods of ischemia. Mucosal clearance of albumin
      remained constant during 240 minutes of perfusion in control tissue and was
      elevated after ischemia-reperfusion. CONCLUSIONS: No deleterious changes were
      noted in jejunum perfused with this isolated circuit, whereas alterations in
      mucosal permeability were present after ischemia-reperfusion. CLINICAL RELEVANCE:
      The isolated perfusion circuit successfully maintained an isolated segment of
      jejunum within physiologic limits, and can be used to evaluate the effects of
      injury and the efficacy of pharmaceuticals to attenuate these changes.

PMID- 12520491
TI  - The effect of two modifications of unilateral arytenoid lateralization on rima
      glottidis area in dogs.
AB  - OBJECTIVES: To evaluate the clinical outcome and percentage increase in rima
      glottidis area achieved using a combined technique of cricoarytenoid and
      thyroarytenoid cartilage lateralization compared with cricoarytenoid cartilage
      lateralization alone in live anesthetized dogs clinically affected with bilateral
      laryngeal paralysis. STUDY DESIGN: Randomized prospective clinical study.
      ANIMALS: Twenty dogs with bilateral laryngeal paralysis. Methods-Bilateral
      laryngeal paralysis was diagnosed by direct laryngoscopy. Each dog was allocated
      randomly to 1 of 2 surgical groups: CAL (cricoarytenoid lateralization) and CTAL
      (cricoarytenoid and thyroarytenoid lateralization). Photographs were taken of
      each larynx before and after surgery, the images were digitized, and the
      preoperative and postoperative areas of each rima glottidis were measured. The
      percentage increase in rima glottidis area produced by each of the arytenoid
      lateralization procedures was compared. Follow-up was obtained by telephone
      survey of owners and referring veterinarians. RESULTS: There was no significant
      difference in mean (+/- SD) percentage increase in rima glottidis area for the
      CAL group (241.5 +/- 42.9%) or the CTAL group (236.4 +/- 44.5%). Clinical follow
      up (median, 18 months postoperatively) indicated 60% of the dogs were still alive
      and only 1 dog had died as a result of complications related to surgery.
      CONCLUSIONS: CTAL for the treatment of canine laryngeal paralysis does not
      significantly increase rima glottidis area compared with CAL alone. The mean
      percentage increase in rima glottidis area obtained with both procedures was
      comparable to previously reported mean increases with CAL in live anesthetized
      dogs. Both procedures resulted in good long-term clinical outcome. CLINICAL
      RELEVANCE: CTAL is as effective as CAL in providing an increased rima glottidis
      for the treatment of bilateral laryngeal paralysis in dogs.

PMID- 12520492
TI  - Use of an ipsilateral vascularized ulnar transposition autograft for limb-sparing
      surgery of the distal radius in dogs: an anatomic and clinical study.
AB  - OBJECTIVE: To develop a surgical technique for using the distal aspect of the
      ulna as a transposition autograft in a distal radial defect and to assess patency
      of vascular supply and viability of the distal ulna in a heterotopic position.
      STUDY DESIGN: Cadaveric study and clinical cases. ANIMALS: Twenty-two normal
      canine thoracic limbs; 3 dogs with distal radial osteosarcoma. METHODS: The
      arteries and veins of 12 limbs were injected with latex. Barium sulfate
      suspension was injected into the brachial artery of 10 other limbs after removal
      of the distal radius only (n = 2), ulna transposition (UT) (n = 6), or no
      procedure (n = 2). The distal ulna grafts were then harvested and decalcified in
      formic acid. The grafts were cut into 3-5 mm transverse sections and radiographed
      with a nonscreen film system to determine filling of intramedullary vessels with
      barium suspension. UT was performed in 3 dogs with distal radial osteosarcoma.
      Bone scintigraphy was performed 2-7 days after surgery to assess viability of the
      transposed ulna graft. RESULTS: Angiography confirmed patency of the caudal
      interosseous artery in all but 2 limbs in which the UT technique was performed;
      however, barium-filled vessels were identified in the medullary cavity of all
      ulnar grafts. Scintigraphy confirmed graft viability in the 3 dogs, all of which
      had good to excellent limb function. CONCLUSIONS: The distal aspect of the canine
      ulna can be used as a vascularized transposition autograft to replace distal
      radial defects, and viability can be maintained. CLINICAL RELEVANCE: The UT
      technique appears to be an acceptable limb-sparing technique for dogs with tumors
      of the distal aspect of the radius.

PMID- 12520493
TI  - Extraosseous cement granuloma associated with total hip replacement in 6 dogs.
AB  - OBJECTIVE: To report the clinical, radiographic, and pathologic features of
      extraosseous cement granuloma (ECG), a low occurrence, long-term complication of
      total hip replacement (THR). STUDY DESIGN: Retrospective clinical study. Sample
      Population-Six client-owned dogs. METHODS: Medical records for 6 dogs that had a
      cemented modular THR and developed ECG were reviewed for the clinical,
      radiologic, and histopathologic findings of ECG. Morphologic and elemental
      analyses of retrieved particles were conducted in 2 dogs using scanning electron
      microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). RESULTS: Three
      golden retrievers and 3 Labrador retrievers had progressive lameness in the
      operated limb 4 to 7 years after THR and developed ECG. Other clinical features
      included an acute deterioration to non-weight bearing associated with pathologic
      fracture of the proximal femur in 2 dogs, and obstipation in 1 dog. In 5 dogs,
      there was a large caseous mass surrounding the proximal femur. Obstipation in 1
      dog was caused by a similar mass adjacent to bone cement used for fixation of the
      acetabular cup. Radiographic changes included a multilobular soft tissue mass,
      containing irregular mineral densities, in the gluteal mass surrounding the
      proximal femur, THR interface deterioration, osteolysis, new bone formation, and
      implant subsidence were consistent with chronic aseptic loosening. The
      histopathologic diagnosis was sterile granuloma associated with a massive
      heterogeneous particulate burden, which was assumed to have resulted from severe
      wear of all prosthesis components. CONCLUSIONS: ECG is a manifestation of severe
      aseptic loosening of cemented total hip replacement, with the generation of wear
      debris probably responsible for granuloma formation. CLINICAL RELEVANCE: Because
      revision can offer a good prognosis in early aseptic femoral loosening, yearly
      radiographic monitoring of the recipients is recommended.

PMID- 12520494
TI  - Treatment of biologically inactive nonunions by a limited en bloc ostectomy and
      compression plate fixation: a review of 17 cases.
AB  - OBJECTIVE: To describe a surgical technique for treatment of biologically
      inactive nonunions using en bloc ostectomy and compression plate fixation and
      clinical outcome in 17 dogs. STUDY DESIGN: Retrospective clinical study. SAMPLE
      POPULATION: Seventeen dogs. METHODS: A transverse ostectomy was performed
      adjacent and parallel to the nonunion to eliminate nonviable tissue and provide a
      new, viable fracture surface with a minimum circumferential contact area of 315
      degrees. With most of the bony column anatomically reconstructed, compression
      plate fixation was used to stabilize the fracture. Autogenous cancellous bone
      grafting was used if a fracture gap was present (<45 degrees of missing
      circumferential bone contact). Resection of bone was limited so that bone
      shortening was less than 20% of the overall bone length. Clinical and
      radiographic follow-up evaluations were obtained whenever possible. RESULTS:
      Complete circumferential bone contact and compression plate fixation was achieved
      after ostectomy in 12 dogs; cancellous bone graft was used in 5 dogs. En bloc
      ostectomy sites were radiographically healed in a median time of 2.5 months after
      surgery in 11 dogs that returned for complete in-hospital follow-up, and
      progressive healing was observed in 3 other dogs, where in-hospital follow-up was
      obtained up to 2 months after surgery. These dogs had a median follow-up time of
      2 months, at which time 6 dogs had no lameness, 4 had minimal lameness, and one
      had moderate lameness. No complications occurred, and no implants were removed.
      CONCLUSIONS: En bloc ostectomy with compression plate fixation was considered
      successful for the treatment of biologically inactive nonunions. A good to
      excellent prognosis can be expected with minimal complications. CLINICAL
      RELEVANCE: Use of an en bloc ostectomy technique for the treatment of
      biologically inactive nonunions permits easy resection of nonviable tissue.
      Subsequent fracture stabilization with compression plate fixation resulted in
      rapid bone healing without complications.

PMID- 12520495
TI  - Re: Tomlinson and Cook. Effects of degree of acetabular rotation after triple
      pelvic osteotomy on the position of the femoral head in relationship to the
      acetabulum. Vet Surg 31:398-403, 2003.

PMID- 12520501
TI  - Ru(salen)-catalyzed asymmetric sulfimidation and subsequent [2,3]sigmatropic
      rearrangement.
AB  - (OC)Ru(salen) 1 was found to catalyze sulfimidation of alkyl aryl sulfides in the
      presence of arylsulfonyl azide with high enantioselectivity, up to 99% ee. When
      the substrates were allylic sulfides, the resulting sulfimides underwent
      [2,3]sigmatropic rearrangement to give the corresponding N-allyl
      toluenesulsulfonamides with greater than 80% ee.

PMID- 12520502
TI  - Ligand-accelerated cadmium-catalyzed asymmetric allylation reactions in aqueous
      media.
AB  - Catalytic asymmetric allylation of aldehydes with allyltributyltin in aqueous
      media has been realized using combinations of cadmium bromide and chiral diamine
      ligands. These ligands were found to accelerate the reactions significantly.

PMID- 12520504
TI  - New bulky chiral Lewis acid catalyst: 3,3'-di(2-mesitylethynyl)binaphthol
      titanium(IV) complex.
AB  - A new chiral Lewis acid catalyst 9 was prepared in situ from a 1:2 molar mixture
      of (R)-3,3'-di(2-mesitylethynyl)binaphthol (6) and titanium(IV) isopropoxide at
      ambient temperature. The 3- and 3'-substituents on 6 were effective for
      preventing undesired aggregation between Ti(IV) complexes and increasing the
      enantioselectivity (up to 82% ee) in the Diels-Alder reaction of methacrolein
      with cyclopentadiene.

PMID- 12520503
TI  - Synthesis of 9-N-cinchona alkaloid peptide hybrid derivatives: preparation and
      conformational study of 9-N-acylamino(9-deoxy)cinchona alkaloids.
AB  - The synthesis and conformational analyses of several 9-N-acylamino(9
      deoxy)cinchona alkaloids is presented. Peptides were connected to cinchona
      alkaloids via a 9-amino group. The synthesis of the new cinchona alkaloid
      derivatives was performed straightforwardly from 9-amino(9-deoxy)dihydroquinidine
      via coupling with carboxylic acid chlorides and several dipeptides. Both alkaloid
      derivatives with the configuration of the corresponding natural product as well
      as its unnatural epimer were studied. The conformations of the prepared
      derivatives in solution were determined by NMR spectroscopy. It is shown that the
      conformation is strongly influenced by the configuration at the 9-position.

PMID- 12520505
TI  - First asymmetric synthesis of chiral beta-iodo Baylis-Hillman esters via tandem
      1,4-conjugate addition/carbonyl coupling reactions.
AB  - A new asymmetric approach to chiral beta-iodo Baylis-Hillman hydroxy esters was
      developed via a tandem asymmetric I-C/C-C formation reaction. The reaction was
      conveniently carried out by slow addition of diethylaluminum iodide into a
      mixture of aldehyde and alpha,beta-acetylenic menthyl ester in dichloromethane at
      -23 degrees C. Excellent geometric selectivity, promising diastereoselectivity
      and modest to high yields (up to 91%) were obtained.

PMID- 12520506
TI  - Studies on the racemization of a stereolabile 5-aryl-thiazolidinedione.
AB  - The enantiomers of the stereolabile peroxisome proliferator-activated receptor
      (PPAR) agonist, 1, were isolated by preparative chiral chromatography and their
      absolute configuration established using a combination of chromatographic and NMR
      methods. Enantiomer interconversion was investigated under a variety of
      conditions, with rapid racemization being observed in most solvents, including
      all aqueous systems studied, irrespective of pH. Rapid racemization in both dog
      and human plasma was confirmed by chiral HPLC with MS detection.

PMID- 12520507
TI  - Stereocontrolled synthesis of 1-acetylen-2,3-di-o-benzyl-tetrahydrofurans, 1,4
      anhydro-arabinitol, and alpha,beta-dihydroxy-gamma-alkyl-butyrolactones.
AB  - This article describes a concise and efficient synthesis of 1-acetylen-2,3-di-O
      benzyl-tetrahydrofurans from tartaric acid esters using as the key step the
      stereocontrolled cyclization of Co(2)(CO)(6)-complexed propargylic diols. This
      molecule led to enantiomerically pure 1,4-anhydro-arabinitol and alpha,beta
      dihydroxy-gamma-alkyl-butyrolactones. In the latter case, the critical methylene
      oxidation at the oxygen vicinal position was performed by RuO(4).

PMID- 12520508
TI  - Concise stereocontrolled routes to fumagillol, fumagillin, and TNP-470.
AB  - A concise, diastereoselective synthesis of (+/-)-fumagillol (3) and formal,
      enantioselective syntheses of the potent angiogenesis inhibitors fumagillin (1)
      and TNP-470 (2) are reported. The origin of asymmetry is a highly
      diastereoselective Diels-Alder reaction using a diene with a chiral oxazolidinone
      auxiliary. The stereochemical course of a key conjugate addition reaction is
      controlled by the cup-shaped architecture of a cis-fused bicyclic enal. Other key
      steps include a facile hetero-Claisen rearrangement and a site-selective
      Sharpless epoxidation.

PMID- 12520510
TI  - Derivatization, complexation, and absolute configurational assignment of chiral
      primary amines: application of exciton-coupled circular dichroism.
AB  - We report here a sensitive method for the determination of the absolute
      configurations of primary amines using exciton-coupled circular dichroism (ECCD).
      The method works on a microgram scale by derivatization of chiral amines with
      quinoline chromophores. Complexation of the chiral ligands with metal ion fixes
      the geometry of the chromophores, resulting in a twist that is governed by the
      asymmetric carbon configuration and steric environment of the amine. The absolute
      configurations of the primary amines can be interpreted from the couplets of the
      ECCD spectra of the derivatized complexes. Crystal structures, 2D NMR studies,
      and semiempirical calculations provide structural evidence for our model.

PMID- 12520509
TI  - Stereostructure-activity studies on agonists at the AMPA and kainate subtypes of
      ionotropic glutamate receptors.
AB  - (S)-Glutamic acid (Glu), the major excitatory neurotransmitter in the central
      nervous system, operates through ionotropic as well as metabotropic receptors and
      is considered to be involved in certain neurological disorders and degenerative
      brain diseases that are currently without any satisfactory therapeutic treatment.
      Until recently, development of selective Glu receptor agonists had mainly been
      based on lead compounds, which were frequently naturally occurring excitants
      structurally related to Glu. These Glu receptor agonists generally contain
      heterocyclic acidic moieties, which has stimulated the use of bioisosteric
      replacement approaches for the design of subtype-selective agonists. Furthermore,
      most of these leads are conformationally restricted and stereochemically well
      defined Glu analogs. Crystallization of the agonist binding domain of the GluR2
      subunit of the (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid
      (AMPA) receptor subtype of ionotropic Glu receptors in the presence or absence of
      an agonist has provided important information about ligand-receptor interaction
      mechanisms. The availability of these binding domain crystal structures has
      formed the basis for rational design of ligands, especially for the AMPA and
      kainate subtypes of ionotropic Glu receptors. This mini-review will focus on
      structure-activity relationships on AMPA and kainate receptor agonists with
      special emphasis on stereochemical and three-dimensional aspects.

PMID- 12520511
TI  - Enantiomerically pure nucleophiles in diastereoselective palladium catalysed
      allylic substitution reactions.
AB  - Enantiomerically pure alpha-amino esters were applied in palladium catalysed
      allylic substitution reactions with moderate diastereoselectivity (up to 70%
      d.e.) using achiral ligands on symmetrical allylic acetates. Nucleophilic
      substitution of amino esters with enantiomerically pure ligands enabled
      diastereoselective ratios of 95:5 to be obtained.

PMID- 12520512
TI  - Determination of the absolute configuration and solution conformation of gossypol
      by vibrational circular dichroism.
AB  - Vibrational circular dichroism (VCD) measurements and density functional theory
      (DFT) calculations were used to obtain the first definitive assignment of the
      absolute configuration for the polyphenolic binaphpthyl dialdehyde gossypol and a
      determination of the solution conformation in CDCl(3). VCD spectra recorded for
      the two resolved enantiomers are near mirror images and excellent agreement
      between the observed IR and VCD spectra and intensity calculations carried out at
      the DFT (B3LYP/6-31G*) level establish the absolute configurations of (+)
      gossypol as P and (-)-gossypol as M, with two conformations in CDCl(3) solution
      that differ in isopropyl group orientation.

PMID- 12520513
TI  - Chiral separation of 2,3-allenoic acid by capillary zone electrophoresis using
      cyclodextrin derivatives.
AB  - In this paper, five of six samples of 2,3-allenoic acid enantiomers were
      separated by capillary zone electrophoresis (CZE) using hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as
      chiral selectors. Using HP-beta-CD for chiral separation, three of the six
      enantiomers were separated. Five experimental conditions including HP-beta-CD
      concentration, pH, buffer concentration, temperature, and running voltage were
      investigated for their influence on separation and migration using enantiomers of
      2-methyl-4-phenyl-2,3-butadienoic acid (A) and 2-(n-propyl)-4-phenyl-2,3
      butadienoic acid (B) as samples. Good separation results were observed when [HP
      beta-CD] = 3-12 mmol/L and pH = 7-9 for samples A and B. The temperature range of
      15-25 degrees C can be selected for convenience. According to the chiral
      separation results, HP-beta-CD and HP-gamma-CD should be valuable selectors to
      separate 2,3-allenoic acids and HP-gamma-CD was suggested to separate the 2,3
      allenoic acid samples with a group at 4-position bulkier than phenyl.

PMID- 12520516
TI  - Role of the vitamin D-endocrine system in the pathophysiology of postmenopausal
      osteoporosis.
AB  - Impaired calcium absorption and impaired adaptation to a low calcium diet are
      common features of aging in women and these processes are even more severely
      impaired in patients with osteoporotic fractures. The calcium absorption defects
      are associated with several abnormalities of the vitamin D-endocrine system
      including secondary hyperparathyroidism, intestinal resistance to 1,25
      dihydroxyvitamin D (1,25(OH)(2)D) action, decreased 1,25(OH)(2)D production due
      to impaired 25(OH)D 1alpha-hydroxylase activity, and, in some elderly persons,
      nutritional deficiency of vitamin D. However, in postmenopausal women, most of
      these abnormalities are normalized by administration of physiologic replacement
      dosages of estrogen and, thus, appear to be secondary consequences of estrogen
      deficiency. Nonetheless, a minority of them, especially nutritional vitamin D
      deficiency and impaired 25(OH)D 1alpha-hydroxylase activity late in life, appear
      to be primary and are independent of estrogen deficiency.

PMID- 12520517
TI  - Vitamin D and autoimmune diabetes.
AB  - The biologically active form of vitamin D, 1,25(OH)(2)D(3), is a potent modulator
      of the immune system as well as a regulator of bone and mineral metabolism.
      Vitamin D-deficiency in infancy and vitamin D receptor gene polymorphisms may be
      risk factors for insulin-dependent Diabetes mellitus (IDDM). 1,25(OH)(2)D(3) and
      its analogs significantly repress the development of insulitis and diabetes in
      the non-obese diabetic (NOD) mouse, a model of human IDDM. 1,25(OH)(2)D(3) may
      modulate IDDM disease pathogenesis by repression of type I cytokines, inhibition
      of dendritic cell maturation, and upregulation of regulatory T cells. The
      function of vitamin D as a genetic and environmental determining factor for IDDM,
      the protective role of 1,25(OH)(2)D(3) and its analogs in a mouse model of IDDM,
      and the possible mechanisms by which this protection occurs will be reviewed.

PMID- 12520518
TI  - Analogs of 1alpha,25-dihydroxyvitamin D3 as pluripotent immunomodulators.
AB  - The active form of vitamin D(3), 1,25(OH)(2)D(3), is known, besides its classical
      effects on calcium and bone, for its pronounced immunomodulatory effects that are
      exerted both on the antigen-presenting cell level as well as directly on the T
      lymphocyte level. In animal models, these immune effects of 1,25(OH)(2)D(3) are
      reflected by a strong potency to prevent onset and even recurrence of autoimmune
      diseases. A major limitation in using 1,25(OH)(2)D(3) in clinical immune therapy
      are the adverse side effects on calcium and on bone. TX527 (19-nor-14,20-bisepi
      23-yne-1,25(OH)(2)D(3)) is a structural 1,25(OH)(2)D(3) analog showing reduced
      calcemic activity associated with enhanced in vitro and in vivo immunomodulating
      capacity compared to the mother-molecule. Indeed, in vitro TX527 is more potent
      that 1,25(OH)(2)D(3) in redirecting differentiation and maturation of dendritic
      cells and in inhibiting phytohemagglutinin-stimulated T lymphocyte proliferation.
      In vivo, this enhanced potency of TX527 is confirmed by a stronger potential to
      prevent type 1 diabetes in nonobese diabetic (NOD) mice and to prolong the
      survival of syngeneic islets grafts, both alone and in combination with
      cyclosporine A, in overtly diabetic NOD mice. Moreover, these in vivo effects of
      TX527 are obtained without the adverse side effects observed for 1,25(OH)(2)D(3)
      itself. We believe therefore that TX527 is a potentially interesting candidate to
      be considered for clinical intervention trails in autoimmune diseases.

PMID- 12520519
TI  - Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance
      regulatory T cells inhibiting allograft rejection and autoimmune diseases.
AB  - Dendritic cells (DCs) not only induce but also modulate T cell activation. 1,25
      dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induces DCs with a tolerogenic phenotype,
      characterized by decreased expression of CD40, CD80, and CD86 costimulatory
      molecules, low IL-12 and enhanced IL-10 secretion. We have found that a short
      treatment with 1,25(OH)(2)D(3) induces tolerance to fully mismatched mouse islet
      allografts that is stable to challenge with donor-type spleen cells and allows
      acceptance of donor-type vascularized heart grafts. This effect is enhanced by co
      administration of mycophenolate mofetil (MMF), a selective inhibitor of T and B
      cell proliferation that has also effects similar to 1,25(OH)(2)D(3) on DCs. Graft
      acceptance is associated with an increased percentage of CD4(+)CD25(+) regulatory
      cells in the spleen and in the draining lymph node that can protect 100% of
      syngeneic recipients from islet allograft rejection. CD4(+)CD25(+) cells, able to
      inhibit the T cell response to a pancreatic autoantigen and to significantly
      delay disease transfer by pathogenic CD4(+)CD25(-) cells, are also induced by
      treatment of adult nonobese diabetic (NOD) mice with 1,25-dihydroxy-16,23Z-diene
      26,27-hexafluoro-19-nor vitamin D(3) (BXL-698). This treatment arrests
      progression of insulitis and Th1 cell infiltration, and inhibits diabetes
      development at non-hypercalcemic doses. The enhancement of CD4(+)CD25(+)
      regulatory T cells, able to mediate transplantation tolerance and to arrest type
      1 diabetes development by a short oral treatment with VDR ligands, suggests
      possible clinical applications of this approach.

PMID- 12520520
TI  - Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin
      D3 and parathyroid hormone.
AB  - The 25-hydroxyvitamin D(3)-24-hydroxylase mRNA is tightly and reciprocally
      regulated by 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and parathyroid hormone
      (PTH). The upregulation of the 24-hydroxylase by 1,25(OH)(2)D(3) is well
      established and occurs at the transcriptional level through two vitamin D
      response elements in the promoter of the gene. However, this induction is blocked
      by the protein synthesis inhibitor cycloheximide (CHX) indicating a protein
      component in the regulation pathway. CHX treatment reduced total vitamin D
      receptor (VDR) protein levels in cells, but reintroduction of VDR and/or retinoid
      X receptor protein into cells by transfection did not reduce the inhibition by
      CHX. This indicates that production of another transcription factor or mRNA
      stabilizing protein synthesized in response to 1,25(OH)(2)D(3) is required for
      optimal accumulation of 24-hydroxylase mRNA. PTH downregulates the 24-hydroxylase
      mRNA by affecting its stability. The half-life of 24-hydroxylase mRNA is reduced
      4.2-fold in AOK-B50 cells by PTH. Untranslated regions of the 24-hydroxylase mRNA
      in reporter gene assays did not confer PTH responsiveness. Further analysis of
      the coding region of the rat 24-hydroxylase may reveal sites of action of PTH.

PMID- 12520521
TI  - Vitamin D target proteins: function and regulation.
AB  - Recent findings have indicated that calbindin-D(28k), the first known target of
      vitamin D action, is present in osteoblasts and protects against TNF and
      glucocorticoid induced apoptosis of osteoblastic cells. Cytokine mediated
      destruction of pancreatic beta cells, a cause of insulin dependent diabetes, is
      also inhibited by calbindin-D(28k). In calbindin-D(28k) transfected pancreatic
      beta cells free radical formation by cytokines is inhibited by calbindin. Thus,
      besides its role as a facilitator of calcium diffusion, calbindin has a major
      role in protecting against cellular degeneration in different cell types. Besides
      calbindin, the other known pronounced effect of 1,25(OH)(2)D(3) in intestine and
      kidney is increased synthesis of 25(OH)D(3) 24-hydroxylase (24(OH)ase) which is
      involved in the catabolism of 1,25(OH)(2)D(3). We have noted that CCAAT enhancer
      binding protein beta (C/EBPbeta) is induced by 1,25(OH)(2)D(3) in kidney and
      osteoblastic cells and can enhance the transcriptional response of 24(OH)ase to
      1,25(OH)(2)D(3). These studies establish C/EBPbeta as a novel 1,25(OH)(2)D(3)
      target gene and indicate a role for C/EBPbeta in 24(OH)ase transcription. These
      studies extend our previous studies related to factors that affect vitamin D
      receptor (VDR) mediated 24(OH)ase transcription (YY1, TFIIB, CBP) and the effect
      of signaling pathways on 24(OH)ase transcription and cofactor recruitment.

PMID- 12520522
TI  - Conventional and tissue-specific inactivation of the 25-hydroxyvitamin D-1alpha
      hydroxylase (CYP27B1).
AB  - Mutations in the human 25-hydroxyvitamin-D(3)-1alpha-hydroxylase (CYP27B1) gene
      cause pseudo vitamin D deficiency rickets (PDDR). The kidney is the main site of
      expression of the CYP27B1 gene, but expression has been documented in other cell
      types, including chondrocytes. We engineered a tissue-specific and a conventional
      knockout of CYP27B1 in mice. The conventional knockout strain reproduced the PDDR
      phenotype. Homozygote mutant animals were treated with 1,25(OH)(2)D(3) or fed a
      high-calcium diet (2% calcium, 1.25% phosphate, 20% lactose) for 5 weeks post
      weaning. Blood biochemistry revealed that both rescue treatments corrected the
      hypocalcemia and secondary hyperparathyroidism. Bone histomorphometry confirmed
      that rickets were cured. The rescue regimen restored the biomechanical properties
      of the bone tissue. Mice carrying the loxP-bearing allele were bred to transgenic
      animals expressing the Cre recombinase in chondrocytes under the control of the
      collagen type II promoter. Genotyping confirmed excision of exon 8 in
      chondrocytes. Serum biochemistry revealed that mineral ion homeostasis is normal
      in mutant animals. Preliminary observation of bone tissue from mutant mice did
      not reveal major changes to the growth plate. Precise histomorphometric analysis
      will be required to assess the impact of chondrocyte-specific inactivation of
      CYP27B1 on the maturation and function of growth plate cells in vivo.

PMID- 12520523
TI  - Synthetic LXXLL peptide antagonize 1,25-dihydroxyvitamin D3-dependent
      transcription.
AB  - The vitamin D receptor (VDR) is known to mediate the biological actions of 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) through its ability to regulate cellular
      programs of gene expression. We identified VDR- and retinoid X receptor (RXR)
      interacting LXXLL peptides using a mammalian two-hybrid system and examined
      whether these molecules could block vitamin D and 9-cis retinoic acid (9-cis RA)
      response. Peptides were identified that were reactive to RXR alone as well as to
      both VDR and RXR. Peptide fusion proteins were then examined in MC3T3 E1 cells
      for their ability to block induction of the osteocalcin promoter by
      1,25(OH)(2)D(3) or stimulation of an RARE-TK reporter by 9-cis RA. Peptides that
      interacted with both VDR and RXR blocked 1,25(OH)(2)D(3)-dependent transcription
      by up to 75%. Peptides that interacted with RXR blocked 9-cis RA induced
      transcription. Two RXR-interacting peptides, however, were also found to block
      1,25(OH)(2)D(3) response effectively. These studies support the idea that
      comodulator recruitment is essential for VDR- and RXR-mediated gene expression
      and that RXR is required for 1,25(OH)(2)D(3)-induced osteocalcin gene
      transcription. This approach may represent a novel means of assessing the
      contribution of RXR in various endogenous biological responses to
      1,25(OH)(2)D(3).

PMID- 12520524
TI  - Vitamin D and bone.
AB  - It is now well established that supraphysiological doses of 1alpha,25
      dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] stimulate bone resorption. Recent
      studies have established that osteoblasts/stromal cells express receptor
      activator of NF-kappaB ligand (RANKL) in response to several bone-resorbing
      factors including 1alpha,25(OH)(2)D(3) to support osteoclast differentiation from
      their precursors. Osteoclast precursors which express receptor activator of NF
      kappaB (RANK) recognize RANKL through cell-to-cell interaction with
      osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of
      macrophage-colony stimulating factor (M-CSF). Osteoprotegerin (OPG) acts as a
      decoy receptor for RANKL. We also found that daily oral administration of
      1alpha,25(OH)(2)D(3) for 14 days to normocalcemic thyroparathyroidectomized
      (TPTX) rats constantly infused with parathyroid hormone (PTH) inhibited the PTH
      induced expression of RANKL and cathepsin K mRNA in bone. The inhibitory effect
      of 1alpha,25(OH)(2)D(3) on the PTH-induced expression of RANKL mRNA occurred only
      with physiological doses of the vitamin. Supraphysiological doses of
      1alpha,25(OH)(2)D(3) increased serum Ca and expression of RANKL in vivo in the
      presence of PTH. These results suggest that the bone-resorbing activity of
      vitamin D does not occur at physiological dose levels in vivo. A certain range of
      physiological doses of 1alpha,25(OH)(2)D(3) rather suppress the PTH-induced bone
      resorption in vivo, supporting the concept that 1alpha,25(OH)(2)D(3) or its
      derivatives are useful for the treatment of various metabolic bone diseases such
      as osteoporosis and secondary hyperparathyroidism.

PMID- 12520525
TI  - Evidence for tissue- and cell-type selective activation of the vitamin D receptor
      by Ro-26-9228, a noncalcemic analog of vitamin D3.
AB  - Our recent studies have shown that the vitamin D analog Ro-26-9228 restores bone
      mineral density without inducing hypercalcemia in osteopenic rats. Our ex vivo
      experiments demonstrated that the analog upregulated gene expression in
      trabecular bone but not in the duodenum of female rats. We examined the mechanism
      for the tissue selectivity of Ro-26-9228 in Caco-2, a human cell line of
      intestinal origin, and hFOB, and a human fetal osteoblast cell line. We found
      that the abilities of Ro-26-9228 and the natural hormone, 1,25-dihydroxyvitamin
      D(3) (1,25D(3)) to induce VDRE-reporter gene expression in transiently
      transfected human osteoblasts are similar. In contrast, in Caco-2 cells, Ro-26
      9228 induces 40-fold less reporter gene expression than 1,25D(3) does. We also
      examined the abilities of the vitamin D receptor (VDR)-ligand complexes from
      these two cell lines to interact with partners of transcription (glucocorticoid
      receptor-interacting protein, VDR-interacting protein, and retinoid X receptor),
      in pull-down assays. These assays revealed that 1,25D(3) induces similar levels
      of interaction of these co-factors with VDR from both osteoblasts and intestinal
      cells. In contrast, Ro-26-9228 induces significant interaction of VDR from
      osteoblast cells with these co-factors, but less of VDR from Caco-2 cells. These
      results suggest that the cellular environment of intestinal cells, unlike that of
      osteoblasts, represses the ability of VDR-Ro-26-9228 complexes to interact with
      transcription partners.

PMID- 12520526
TI  - Molecular basis of the selective activity of vitamin D analogues.
AB  - More than 2,000 synthetic analogues of the biological active form of vitamin D,
      1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), are presently known.
      Basically, all of them interfere with the molecular switch of nuclear
      1alpha,25(OH)(2)D(3) signaling, which is the complex of the vitamin D receptor
      (VDR), the retinoid X receptor (RXR), and a 1alpha,25(OH)(2)D(3) response element
      (VDRE). Central element of this molecular switch is the ligand-binding domain
      (LBD) of the VDR, which can be stabilized by a 1alpha,25(OH)(2)D(3) analogue
      either in its agonistic, antagonistic, or non-agonistic conformation. The
      positioning of helix 12 of the LBD is of most critical importance for these
      conformations. In each of the three conformations, the VDR performs different
      protein-protein interactions, which then result in a characteristic functional
      profile. Most 1alpha,25(OH)(2)D(3) analogues have been identified as agonists, a
      few are antagonists (e.g., ZK159222 and TEI-9647), and only Gemini and some of
      its derivatives act under restricted conditions as non-agonists. The functional
      profile of some 1alpha,25(OH)(2)D(3) analogues, such as EB1089 and Gemini, can be
      modulated by protein and DNA interaction partners of the VDR. This provides them
      with some selectivity for DNA-dependent and -independent signaling pathways and
      VDRE structures.

PMID- 12520527
TI  - Rat cytochrome P450C24 (CYP24) does not metabolize 1,25-dihydroxyvitamin D2 to
      calcitroic acid.
AB  - 1alpha-Hydroxy-23 carboxy-24,25,26,27-tetranorvitamin D(3) (calcitroic acid) is
      known to be the major water-soluble metabolite produced during the deactivation
      of 1,25-(OH)(2)D(3). This deactivation process is carried out exclusively by the
      multicatalytic enzyme CYP24 and involves a series of oxidation reactions at C(24)
      and C(23) leading to side-chain cleavage and, ultimately, formation of the
      calcitroic acid. Like 1,25-(OH)(2)D(3), 1alpha,25-1,25-(OH)(2)D(2) is also known
      to undergo side-chain oxidation and side-chain cleavage to form calcitroic acid
      (Zimmerman et al. [2001]. 1,25-(OH)(2)D(2) differs from 1,25-(OH)(2)D(3) by the
      presence of a double bond at C(22) and a methyl group at C(24). To date, there
      have been no studies detailing the participation of CYP24 in the production of
      calcitroic acid from 1,25-(OH)(2)D(2). We, therefore, studied the metabolism of
      1,25-(OH)(2)D(3) and 1,25-(OH)(2)D(2) using a purified rat CYP24 system. Lipid
      and aqueous-soluble metabolites were prepared for characterization. Aqueous
      soluble metabolites were subjected to reverse-phase high-pressure liquid
      chromatography (HPLC) analysis. As expected, 1,23(OH)(2)-24,25,26,27-tetranor D
      and calcitroic acid were the major lipid and aqueous-soluble metabolites,
      respectively, when 1,25-(OH)(2)D(3) was used as substrate. However, when 1,25
      (OH)(2)D(2) was used as substrate, 1,24(R),25-(OH)(3)D(2) was the major lipid
      soluble metabolite with no evidence for the production of either 1,23(OH)(2)
      24,25,26,27-tetranor D or calcitroic acid. Apparently, the CYP24 was able to 24
      hydroxylate 1,25-(OH)(2)D(2), but was unable to effect further changes, which
      would result in side-chain cleavage. These data suggest that the presence of
      either the double bond at C(22) or the C(24) methyl group impedes the metabolism
      of 1,25-(OH)(2)D(2) to calcitroic acid by CYP24 and that enzymes other than CYP24
      are required to effect this process.

PMID- 12520528
TI  - A new active vitamin D analog, ED-71, causes increase in bone mass with
      preferential effects on bone in osteoporotic patients.
AB  - As a candidate for active vitamin D analogs that have selective effects on bone,
      1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71) has been
      synthesized and is currently under clinical trials. In ovariectomized rat model
      for osteoporosis, ED-71 caused an increase bone mass at the lumbar vertebra to a
      greater extent than 1alpha-hydroxyvitamin D3 (alfacalcidol), while enhancing
      calcium absorption and decreasing serum parathyroid hormone levels to the same
      degree as alfacalcidol. ED-71 lowered the biochemical and histological parameters
      of bone resorption more potently than alfacalcidol, while maintaining bone
      formation markers. An early phase II clinical trial was conducted with 109
      primary osteoporotic patients. The results indicate that oral daily
      administration of ED-71 (0.25, 0.5, 0.75, and 1.0 microgram) for 6 months
      increased lumbar bone mineral density in a dose-dependent manner without causing
      hypercalcemia and hypercalciuria. ED-71 also exhibited a dose-dependent
      suppression of urinary deoxypyridinoline with no significant reduction in serum
      osteocalcin. These results demonstrate that ED-71 has preferential effects on
      bone with diminished effects on intestinal calcium absorption. ED-71 offers
      potentially a new modality of therapy for osteoporosis with selective effects on
      bone.

PMID- 12520529
TI  - Vitamin D regulated keratinocyte differentiation: role of coactivators.
AB  - 1,25 Dihydroxyvitamin D (1,25(OH)(2)D) regulates the differentiation of
      keratinocytes. 1,25(OH)(2)D raises intracellular free calcium (Cai) as a
      necessary early step toward stimulating differentiation. 1,25(OH)(2)D induces the
      calcium sensing receptor (CaR) in keratinocytes and enhances the calcium response
      of these cells. Activation of the CaR by calcium increases intracellular free
      calcium by a mechanism involving phospholipase C (PLC) cleavage of
      phosphatidylinositolbisphosphate into inositoltrisphosphate (IP(3)) and
      diacylglycerol (DG). 1,25(OH)(2)D induces the family of PLCs. PLC-gamma1 has a
      DR6 VDRE in its promoter which binds and is activated by VDR/RAR rather than
      VDR/RXR. The involucrin gene, which encodes a critical component of the cornified
      envelope, contains a DR3 VDRE in its promoter that acts in conjunction with a
      nearby AP-1 site. The sequential regulation of these genes is critical for the
      differentiation process. In undifferentiated keratinocytes, the VDR binds
      preferentially to the DRIP complex of coactivators. However, with differentiation
      DRIP 205 is no longer produced, and the VDR switches partners to the SRC family
      (SRC2 and 3). These studies suggest that at least part of the sequential
      activation of genes required during keratinocyte differentiation is regulated by
      the change (availability) of these different coactivator complexes.

PMID- 12520530
TI  - Vitamin D: A millenium perspective.
AB  - Vitamin D is one of the oldest hormones that have been made in the earliest life
      forms for over 750 million years. Phytoplankton, zooplankton, and most plants and
      animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin
      D is critically important for the development, growth, and maintenance of a
      healthy skeleton from birth until death. The major function of vitamin D is to
      maintain calcium homeostasis. It accomplishes this by increasing the efficiency
      of the intestine to absorb dietary calcium. When there is inadequate calcium in
      the diet to satisfy the body's calcium requirement, vitamin D communicates to the
      osteoblasts that signal osteoclast precursors to mature and dissolve the calcium
      stored in the bone. Vitamin D is metabolized in the liver and then in the kidney
      to 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. 1,25(OH)(2)D receptors (VDR) are
      present not only in the intestine and bone, but in a wide variety of other
      tissues, including the brain, heart, stomach, pancreas, activated T and B
      lymphocytes, skin, gonads, etc. 1,25(OH)(2)D is one of the most potent substances
      to inhibit proliferation of both normal and hyperproliferative cells and induce
      them to mature. It is also recognized that a wide variety of tissues, including
      colon, prostate, breast, and skin have the enzymatic machinery to produce
      1,25(OH)(2)D. 1,25(OH)(2)D and its analogs have been developed for treating the
      hyperproliferative disease psoriasis. Vitamin D deficiency is a major
      unrecognized health problem. Not only does it cause rickets in children,
      osteomalacia and osteoporosis in adults, but may have long lasting effects.
      Chronic vitamin D deficiency may have serious adverse consequences, including
      increased risk of hypertension, multiple sclerosis, cancers of the colon,
      prostate, breast, and ovary, and type 1 diabetes. There needs to be a better
      appreciation of the importance of vitamin D for overall health and well being.

PMID- 12520531
TI  - Novel regulators of vitamin D action and metabolism: Lessons learned at the Los
      Angeles zoo.
AB  - We undertook an investigation of an outbreak of rachitic bone disease in the
      Emperor Tamarin New World primate colony at the Los Angeles Zoo in the mid-1980s.
      The disease phenotype resembled that observed in humans with an inactivating
      mutation of the vitamin D receptor (VDR), hypocalcemia, high 1,25
      dihydroxyvitamin D (1,25-(OH)(2)D) levels, and rickets in rapidly growing
      adolescent primates. In contrast to the human disease, the New World primate VDR
      was functionally normal in all respects. The proximate cause of vitamin D hormone
      resistance in New World primates was determined to be the constitutive
      overexpression of a heterogeneous nuclear ribonucleoprotein in the A family which
      we coined the vitamin D response element binding protein (VDRE-BP). VDRE-BP
      competed in trans with the VDR-retinoid X receptor (RXR) for binding to the
      vitamin D response element. VDRE-BP-legislated resistance to 1,25-(OH)(2)D was
      antagonized (i.e., compensated) by another set of constitutively overexpressed
      proteins, the hsp-70-related intracellular vitamin D binding proteins (IDBPs).
      IDBPs, present but expressed at much lower levels in Old World primates including
      man, exhibited a high capacity for 25-hydroxylated vitamin D metabolites and
      functioned to traffic vitamin Ds to specific intracellular destinations to
      promote their action and metabolism.

PMID- 12520532
TI  - Prostatic 25-hydroxyvitamin D-1alpha-hydroxylase and its implication in prostate
      cancer.
AB  - Evidence suggests that vitamin D may have a protective role for prostate cancer.
      1alpha,25-Dihydroxyvitamin D [1alpha,25(OH)(2)D] inhibits growth and induces
      differentiation of prostate cells. 25-Hydroxyvitamin D-1alpha-hydroxylase [1alpha
      OHase], the enzyme that is responsible for the synthesis of 1alpha,25(OH)(2)D, is
      expressed in cultured prostate cells. We observed a marked decrease in 1alpha
      OHase activity in prostate cancer cells, suggesting some defect of the 1alpha
      OHase in these cells. To investigate whether the defect was due to dysregulation
      of the enzyme at the promoter level, a series of deletion constructs of the
      promoter was synthesized and incorporated upstream into the luciferase reporter
      gene. Two regions were identified with high basal activity in transfected normal
      prostate cell line (PZHPV-7), -1100 bp (AN2), and -394 bp (AN5) upstream of ATG
      start site of the 1alpha-OHase gene. When the reporter gene with either AN2 or
      AN5 was transfected into prostate cancer cell lines, we observed a lower basal
      promoter activity in PC-3 cells and DU145 cells than that found in PZHPV-7 cells
      for both constructs, and a loss of promoter activity in LNCaP cells. Thus, the
      results suggest that the defect in enzyme activity may result from the decreased
      promoter activity in prostate cancer cells.

PMID- 12520533
TI  - Effects of 1alpha,25(OH)2D3 and its analogs on dendritic cell function.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) and non-calcemic vitamin D
      analogs induce a persistent state of immaturity in dendritic cells both in vitro
      and in vivo. These effects are transcriptional in nature, involve alterations in
      surface ligands as well as cytokine synthesis and release, and are dependent upon
      the presence of the vitamin D receptor. The vitamin D endocrine system could also
      play a role in altering immune function in normal physiological conditions.
      Distinct differences exist in lymph node dendritic cells of vitamin D receptor
      null mutant mice when compared to normal mice.

PMID- 12520534
TI  - Vitamin D regulation of the renin-angiotensin system.
AB  - The renin-angiotensin system (RAS) plays a central role in the regulation of
      blood pressure, electrolyte, and volume homeostasis. Epidemiological and clinical
      studies have long suggested an association of inadequate sunlight exposure or low
      serum 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels with high blood
      pressure and/or high plasma renin activity, but the mechanism is not understood.
      Our recent discovery that 1,25(OH)(2)D(3) functions as a potent negative
      endocrine regulator of renin gene expression provides some insights into the
      mechanism. The concept of vitamin D regulation of blood pressure through the RAS
      opens a new avenue to our understanding of the physiological functions of the
      vitamin D endocrine system, and provides a basis for exploring the potential use
      of vitamin D analogues in prevention and treatment of hypertension.

PMID- 12520535
TI  - Intestinal calcium absorption: Molecular vitamin D mediated mechanisms.
AB  - Rickets and hyperparathyroidism caused by a defective Vitamin D receptor (VDR)
      can be prevented in humans and animals by high calcium intake, suggesting that
      intestinal calcium absorption is critical for 1,25(OH)(2) vitamin D [1,25
      (OH)(2)D(3)] action on calcium homeostasis. We assessed the rate of serum (45)Ca
      accumulation within 10 min after oral gavage in two strains of VDR-knock out (KO)
      mice (Leuven and Tokyo KO) and observed a threefold lower area under the curve in
      both KO-strains. Moreover, we evaluated the expression of intestinal candidate
      genes, belonging to a new class of calcium channels (TRPV), involved in
      transcellular calcium transport. The calcium transport protein ECaC2 was more
      abundantly expressed at mRNA level than ECaC1 in duodenum, but both were
      considerably reduced (ECaC2 > 90%, ECaC1 > 60%) in the two VDR-KO strains on a
      normal calcium diet. Calbindin-D(9K) expression was only significantly decreased
      in the Tokyo KO, whereas PMCA(1b) expression was normal in both VDR-KOs. In
      Leuven wild type mice, a high calcium diet inhibited (> 90%), and 1,25(OH)(2)D(3)
      or low calcium diet induced (sixfold) duodenal ECaC2 expression and, to a lesser
      degree, ECaC1 and calbindin-D(9K) expression. In Leuven KO mice, however, high or
      low calcium intake decreased calbindin-D(9K) and PMCA(1b) expression, whereas
      both ECaC mRNA expressions remained consistently low on any diet. These results
      suggest that the expression of the novel duodenal epithelial calcium channels (in
      particular ECaC2 or TRPV6) is strongly vitamin D dependent and that calcium
      influx, probably interacting with calbindin-D(9K), should be considered as a rate
      limiting step in the process of vitamin D dependent active calcium absorption.

PMID- 12520536
TI  - Intranuclear trafficking of transcription factors: Requirements for vitamin D
      mediated biological control of gene expression.
AB  - The architecturally associated subnuclear organization of nucleic acids and
      cognate regulatory factors suggest functional interrelationships between nuclear
      structure and gene expression. Mechanisms that contribute to the spatial
      distribution of transcription factors within the three-dimensional context of
      nuclear architecture control the sorting of regulatory information as well as the
      assembly and activities of sites within the nucleus that support gene expression.
      Vitamin D control of gene expression serves as a paradigm for experimentally
      addressing mechanisms that govern the intranuclear targeting of regulatory
      factors to nuclear domains where transcription of developmental and tissue
      specific genes occur. We will present an overview of molecular, cellular,
      genetic, and biochemical approaches that provide insight into the trafficking of
      regulatory factors that mediate vitamin D control of gene expression to
      transcriptionally active subnuclear sites. Examples will be presented that
      suggest modifications in the intranuclear targeting of transcription factors
      abrogate competency for vitamin D control of skeletal gene expression during
      development and fidelity of gene expression in tumor cells.

PMID- 12520537
TI  - Expression, structure-function, and molecular modeling of vitamin D P450s.
AB  - Although vitamin D(3) is a natural product of a sunlight-mediated process in the
      skin, the secosteroid's biological function is dependent upon specific cytochrome
      P450 enzymes that mediate the parent vitamin's bioactivation and inactivation.
      Cytochrome P450C1 (CYP27B1) is the regulatory rate-limiting enzyme that directs
      the bioactivation process through introduction of a C-1alpha hydroxyl group. The
      resultant 1,25-dihydroxyvitamin D(3) (1,25D) is the biologically active
      secosteroid hormone that directs the multitude of vitamin D-dependent actions
      involved with calcium homeostasis, cellular differentiation and growth, and the
      immune response. The circulating and cellular level of 1,25D is regulated through
      a coordinated process involving the hormone's synthesis and degradation. Central
      to the degradation and turnover of 1,25D is the regulatory multi-catalytic
      cytochrome P450C24 (CYP24) enzyme that directs the introduction of C-24R groups
      onto targeted 25-hydroxy substrates. Discussed in this article is the action of
      the rat CYP24 to catalyze the side-chain oxidation and cleavage of 25
      hydroxylated vitamin D metabolites. Expression and characterization of purified
      recombinant rat CYP24 is discussed in light of mutations directed at the enzyme's
      active site.

PMID- 12520538
TI  - Inhibition of prostate cancer growth by vitamin D: Regulation of target gene
      expression.
AB  - Prostate cancer (PCa) cells express vitamin D receptors (VDR) and 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inhibits the growth of epithelial cells
      derived from normal, benign prostate hyperplasia, and PCa as well as established
      PCa cell lines. The growth inhibitory effects of 1,25(OH)(2)D(3) in cell cultures
      are modulated tissue by the presence and activities of the enzymes 25
      hydroxyvitamin D(3) 24-hydroxylase which initiates the inactivation of
      1,25(OH)(2)D(3) and 25-hydroxyvitamin D(3) 1alpha-hydroxylase which catalyses its
      synthesis. In LNCaP human PCa cells 1,25(OH)(2)D(3) exerts antiproliferative
      activity predominantly by cell cycle arrest through the induction of IGF binding
      protein-3 (IGFBP-3) expression which in turn increases the levels of the cell
      cycle inhibitor p21 leading to growth arrest. cDNA microarray analyses of primary
      prostatic epithelial and PCa cells reveal that 1,25(OH)(2)D(3) regulates many
      target genes expanding the possible mechanisms of its anticancer activity and
      raising new potential therapeutic targets. Some of these target genes are
      involved in growth regulation, protection from oxidative stress, and cell-cell
      and cell-matrix interactions. A small clinical trial has shown that
      1,25(OH)(2)D(3) can slow the rate of prostate specific antigen (PSA) rise in PCa
      patients demonstrating proof of concept that 1,25(OH)(2)D(3) exhibits therapeutic
      activity in men with PCa. Further investigation of the role of calcitriol and its
      analogs for the therapy or chemoprevention of PCa is currently being pursued.

PMID- 12520539
TI  - Inhibitors of vitamin D hydroxylases: structure-activity relationships.
AB  - Aiming at new drugs to efficiently treat diseases, in which either increased or
      decreased levels of active vitamin D are desirable, we have designed some 400
      structurally different azole-type inhibitors and examined their capacity to
      selectively block vitamin D metabolism by CYP24 or synthesis by CYP27B, in human
      keratinocytes. Based on resulting data, we built pharmacophore models of the
      active sites using commercial software. The overlay of potent selective compounds
      indicated similar docking modes in the two-substrate pockets and allowed for
      identification of bioactive conformations. Superimposing these bioactive
      conformations with low energy conformers of 25(OH)D(3) suggested that the
      substrate-mimicked by strong inhibitors in size, shape and lipophilic character
      binds to both enzymes in 6s-trans configuration. Pharmacophoric models implied a
      similar geometry of the substrate sites, nevertheless specific features of CYP24
      and CYP27B could be defined. Bulky substituents in alpha-position to the azole
      caused selectivity for CYP24, whereas bulky substituents in beta-position could
      result in selectivity for CYP27B. Moreover, studies with small sterically
      restricted inhibitors revealed a probable location of the 3-OH-group of
      25(OH)D(3) in CYP27B. In the absence of crystal structures, our inhibitors are
      valuable tools to model and understand the active sites of vitamin D
      hydroxylases, resulting in the design of powerful, selective therapeutics.

PMID- 12520540
TI  - Rationale for active vitamin D and analogs in the treatment of osteoporosis.
AB  - In 1981, Chugai Pharmaceutical succeeded in marketing alfacalcidol, a prodrug of
      calcitriol, as a therapeutic agent for renal osteodystrophy. In 1983, Chugai
      succeeded in extending the application of alfacalcidol to the treatment of
      osteoporosis as well. Clinicians in Japan have accepted alfacalcidol as a remedy
      for osteoporosis. However, the use of calcitriol and its analogs for the
      treatment of osteoporosis is still controversial. Some misunderstandings exist
      internationally about the efficacy of the active form of vitamin D for the
      treatment of osteoporosis. It is important to emphasize that patients with
      osteoporosis have intestinal calcium malabsorption and dysfunction in renal
      activation of vitamin D. When massive doses of parent vitamin D were administered
      to OVX rats, bone mass increased, but surprisingly, many porotic area were
      observed in the cortical bone. On the other hand, administration of alfacalcidol
      increased physiological bone without porotic observation. It is necessary to give
      the active form of vitamin D, D-hormone, with an RDA-equivalent supply of
      calcium. Alfacalcidol forms physiological strong bones that are hardly fractured
      by regulating calcium and bone metabolism. We proposed a new vitamin D analog,
      2beta (3-hydroxypropoxy)calcitriol [ED-71] as a therapeutic drug for
      osteoporosis, which is more potent than calcitriol. ED-71 is now being
      investigated in phase 2 clinical studies in Japan. ED-71 will appear as more
      improved drugs for osteoporosis until 2010.

PMID- 12520541
TI  - Mechanisms of intestinal calcium absorption.
AB  - Calcium is absorbed in the mammalian small intestine by two general mechanisms: a
      transcellular active transport process, located largely in the duodenum and upper
      jejunum; and a paracellular, passive process that functions throughout the length
      of the intestine. The transcellular process involves three major steps: entry
      across the brush border, mediated by a molecular structure termed CaT1,
      intracellular diffusion, mediated largely by the cytosolic calcium-binding
      protein (calbindinD(9k) or CaBP); and extrusion, mediated largely by the
      CaATPase. Chyme travels down the intestinal lumen in approximately 3 h, spending
      only minutes in the duodenum, but over 2 h in the distal half of the small
      intestine. When calcium intake is low, transcellular calcium transport accounts
      for a substantial fraction of the absorbed calcium. When calcium intake is high,
      transcellular transport accounts for only a minor portion of the absorbed
      calcium, because of the short sojourn time and because CaT1 and CaBP, both rate
      limiting, are downregulated when calcium intake is high. Biosynthesis of CaBP is
      fully and CaT1 function is approximately 90% vitamin D-dependent. At high calcium
      intakes CaT1 and CaBP are downregulated because 1,25(OH)(2)D(3), the active
      vitamin D metabolite, is downregulated.

PMID- 12520542
TI  - Proprotein convertases regulate activity of prostate epithelial cell
      differentiation markers and are modulated in human prostate cancer cells.
AB  - Prostate derived factor (PDF) is a member of transforming growth factor-beta (TGF
      beta) superfamily proteins involved in differentiation of the prostate
      epithelium. Proprotein convertases (PCs) such as furin are thought to mediate the
      processing of TGF-beta superfamily. In the present study, we demonstrated for the
      first time that human prostate cancer cell lines differentially synthesize and
      secret prostate derived factor (PDF), and that PDF secreted by LNCaP is processed
      by PCs. Exposure of LNCaP cells to the decanoyl-Arg-Val-Lys-Arg
      chloromethylketone (CMK), a synthetic furin-like protease inhibitor, inhibited
      PDF processing and resulted in the loss of luminal cell phenotype and induction
      of basal cell phenotype in LNCaP cells as demonstrated by alternations in the
      expression of cytokeratins 8, 14, 18, and 19, markers of prostate epithelial cell
      differentiation. These results suggest that proprotein convertases may be
      involved in the regulation of prostate epithelial cell differentiation, and may
      be an important target of prostate cancer therapy.

PMID- 12520543
TI  - Regulation of imprinting: A multi-tiered process.
AB  - Although most mammalian genes are expressed from both alleles, there is a small
      group of special genes which are imprinted so that only one of the parental
      alleles is actually expressed in target cells. This epigenetic process involves
      regulation at a number of different stages of development and is very complex. In
      principle, imprinted gene regions must be marked in cis in the gametes using
      epigenetic features capable of being maintained through cell division and able to
      direct multigenic monoallelic expression in differentiated cells of the mature
      organism. The difference between alleles must be erased during early
      gametogenesis to allow the imprint to be reset in the mature gametes. In this
      review we will summarize what is currently known about the molecular mechanisms
      which mediate these steps.

PMID- 12520544
TI  - HGF/SF-met signaling in the control of branching morphogenesis and invasion.
AB  - Hepatocyte growth factor/Scatter factor (HGF/SF) is a multifunctional growth
      factor which can induce diverse biological events. In vitro, these include
      scattering, invasion, proliferation and branching morphogenesis. In vivo, HGF/SF
      is responsible for many processes during embryonic development and a variety of
      activities in adults, and many of these normal activities have been implicated in
      its role in tumorgenesis and metastasis. The c-Met receptor tyrosine kinase is
      the only known receptor for HGF/SF and mediates all HGF/SF induced biological
      activities. Upon HGF/SF stimulation, the c-Met receptor is tyrosine
      phosphorylated which is followed by the recruitment of a group of signaling
      molecules and/or adaptor proteins to its cytoplasmic domain and its multiple
      docking sites. This action leads to the activation of several different signaling
      cascades that form a complete network of intra and extracellular responses.
      Different combinations of signaling pathways and signaling molecules and/or
      differences in magnitude of responses contribute to these diverse series of
      HGF/SF-Met induced activities and most certainly are influenced by cell type as
      well as different cellular environments. In this review, we focus on HGF/SF
      induced branching morphogenesis and invasion, and bring together recent new
      findings which provide insight into how HGF/SF, via c-Met induces this response.

PMID- 12520545
TI  - Gene therapy for tissue regeneration.
AB  - Tissue repair and regeneration are the normal biological responses of many
      different tissues in the body to injury. During the healing process, profound
      changes occur in cell composition and extracellular matrix (ECM) formation.
      Fibroblasts and equivalent reparative cells migrate to the wounded area and
      subsequently proliferate. These cells and reparative cells from the surrounding
      tissue are responsible for the rapid repair which results in tissue regeneration.
      Growth factors, one of which is transforming growth factor-beta (TGF-beta),
      stimulate fibroblasts and smooth muscle cells to proliferate and synthesize ECM
      proteins. This process of early repair provides a rapid way to restore new tissue
      and mechanical integrity. This early tissue repair process is normally followed
      by involution, which requires the production and activation of proteases, tissue
      maturation and remodeling, reorganization and finally regeneration. Alternately,
      failure to replace the critical components of the ECM, including elastin and
      basement membrane, results in abnormal regeneration of the epithelial cell layer.
      Although remodeling should occur during healing, provisional repair may be
      followed by excessive synthesis and deposition of collagen, which results in
      irreversible fibrosis and scarring. This excessive fibrosis which occurs in
      aberrant healing is at least in part mediated by persistent TGF-beta. Because of
      the central role of collagen in the wound healing process, the pharmacological
      control of collagen synthesis has been of paramount importance as a possible way
      to abrogate aberrant healing and prevent irreversible fibrosis. Fibrosis is an
      abnormal response to tissue injury.

PMID- 12520546
TI  - Dwarf male of Symbion pandora (cycliophora).
AB  - This study clarifies the identity and development of the male in the life cycle
      of Symbion pandora. The male is not produced directly by the feeding stage, as
      previously thought, but arises as a distinct individual from budding cells inside
      an intermediate stage named the Prometheus larva. The morphology and the
      development of the two distinct stages are described with light and electron
      microscopy. Furthermore, the following terminology is suggested to clearly
      distinguish between the different individuals: 1) the Prometheus larva, which is
      the free-swimming individual being produced inside the feeding stage; 2) the
      attached Prometheus larva on the feeding stage, which mostly degenerates
      following settlement, except for the internal budding cells; and 3) the dwarf
      male, which is the ciliated, sexually mature stage. The budding cells inside the
      attached Prometheus larva usually develop two internal dwarf males. Each dwarf
      male is heavily ciliated and has a well-developed nervous system with a
      relatively large brain, numerous gland and muscle cells, testis with bundles of
      sperm, and one penial structure. The male lacks a gut, as in the other free
      stages in the life cycle of Symbion pandora. This study also indicates that the
      dwarf male is freed from the attached Prometheus larva. Copulation, which has not
      been observed yet, probably takes place between a free-swimming male and the
      female, either while the female is released or afterwards.

PMID- 12520547
TI  - Functional-adaptive anatomy of the axial skeleton of some extant marsupials and
      the paleobiology of the paleocene marsupials Mayulestes ferox and Pucadelphys
      andinus.
AB  - In this study, the axial skeletons of two Early Paleocene marsupials, Mayulestes
      ferox and Pucadelphys andinus, were analyzed functionally and compared to that of
      six South American and three Australian species of extant marsupials. In the case
      of the South American opossums, myological data of the epaxial musculature were
      collected and analyzed and osteological-myological associations were related to
      locomotor behavior. Various features of the vertebral column that relate to diet
      or to locomotor or postural patterns were pointed out. These features include:
      the craniocaudal development of the neural process of the axis; the position of
      the anticlinal vertebra; the morphology of the neural processes of the
      thoracolumbar vertebrae (orientation, length, and craniocaudal width); the
      length, orientation, and curvature of the transverse processes of the lumbar
      vertebrae; and the length and robustness of the caudal vertebrae. In both fossil
      forms the vertebral column is mobile and allows a great range of flexion and
      extension of the spine, more so than in most of the living didelphids. It is
      emphasized here that the analysis of the axial skeleton complements and improves
      the conclusions provided by the forelimb and hindlimb analyses. It is proposed
      that Mayulestes and Pucadelphys represent an ancestral morphotype suggesting that
      the generalized type of locomotion of Paleocene marsupials was partly terrestrial
      with some climbing ability.

PMID- 12520548
TI  - Morphometry of Macaca mulatta forelimb. III. Moment arm of shoulder and elbow
      muscles.
AB  - The conversion of muscle activity into smooth, purposeful movement of the limb
      depends complexly on the morphometry of muscles and their mechanical action on
      the skeleton. Although nonhuman primates are common subjects in motor control
      experiments (Scott [2000] Can J Physiol Pharmacol 78:923-933), little information
      is available on the morphometric properties of their upper limbs. One key
      variable is muscle moment arm, or mechanical advantage, which defines how linear
      motion or force of a muscle is translated into angular motion or torque at a
      joint. This study reports moment arm values with respect to joint angle
      (flexion/extension) of 14 muscles spanning the shoulder and elbow in Macaca
      mulatta. The magnitude of moment arm values ranged widely across muscles. In some
      muscles mechanical advantage remained constant with joint angle, whereas the
      moment arm of others varied strongly. The angle (Theta(f)(o)) at which optimal
      fascicle length (L(f)(o)) occurred showed strong trends, where the elbow-spanning
      muscles had Theta(f)(o) values clustered at mid-flexion and the shoulder
      musculature Theta(f)(o) values tended to be grouped around the neutral joint
      angle of 0 degrees. Estimates of peak muscle torque for flexor and extensor
      muscle groups at each joint were surprisingly similar in both magnitude and
      dependency on joint angle. The present study, along with the previous two in this
      series (Cheng and Scott [2000] J Morphol 245:206-224; Singh et al. [2002] J
      Morphol 251:323-332), provides a comprehensive description of the morphology of
      the proximal portion of the limb suitable for the development of a
      musculoskeletal model of the M. mulatta upper limb.

PMID- 12520549
TI  - Positional information by Rauber's sickle and a new look at the mechanisms of
      primitive streak initiation in avian blastoderms.
AB  - The present experimental in vitro study suggests that a primitive streak (PS) in
      avian blastoderms is induced by diffusion of morphogenetic substances emanating
      from Rauber's sickle. Indeed, even without direct contact between a quail
      Rauber's sickle and the reacting upper layer (by interposition of a vitelline
      membrane), a PS can be induced in the isolated area centralis or antisickle
      region of unincubated chicken blastoderms. The so-formed PSs are localized below
      the vitelline membrane in the immediate neighborhood of the apposed Rauber's
      sickle material. This seems to indicate that Rauber's sickle organizes the
      formation of the avian PS according to the basic concept of "positional
      information." The morphogenetic substances seem to have an effect only on the
      formation of a PS. Each part of Rauber's sickle seems to have, point by point,
      the same thickening and PS-inducing effect on each corresponding part of the
      underlying upper layer (UL). By a mechanism of sliding over the basement membrane
      and fusion, this finally results in the formation of one single median PS. Our
      study shows that a PS can be induced in the total absence of hypoblast (sickle
      endoblast) or caudal marginal zone, by only the presence of Rauber's sickle
      material. In contrast, the differentiation of mesoblast into blood islands under
      the influence of Rauber's sickle and neural tissue development are impaired by
      the interposition of a vitelline membrane. The latter could be due to the absence
      of a normal interaction of Rauber's sickle-derived sickle endoblast with
      endophyll and/or upper layer and the absence of cranial migration of the
      mesoblast. Thus, earlier studies and the present study indicate the existence of
      a temporospatially bound cascade of gastrulation and neurulation phenomena and
      blood island formation in the avian blastoderm, starting from Rauber's sickle,
      the primary major organizer with inducing, inhibiting, and dominating potencies.
      The latter not only plays a role by secretion of signaling molecules, but also
      influences development by its cell lineages (junctional endoblast and sickle
      endoblast).

PMID- 12520550
TI  - Microscopic anatomy of the orbital Harderian gland in the common tree shrew
      (Tupaia glis).
AB  - The orbital Harderian gland of the common tree shrew (Tupaia glis) was
      investigated at the macroscopic and microscopic levels. In the glands of both
      sexes only one acinar cell type was found. The cell is characterized by the
      presence of numerous lipid vacuoles of variable size and by a small number of PAS
      positive, electron-dense granules distributed throughout the cytoplasm, which are
      predominant at the basal portion of each acinar cell. The duct system is well
      developed within the gland. The content of lipid vacuoles within the acinar cells
      is secreted from the apical portions by exocytosis, indicating the exocrine
      function of the organ. Apart from the lipid vacuoles, both acinar and ductal
      luminal contents of the Harderian gland also contain accretion of electron-dense
      materials. The vascularization within the Harderian gland is unique in that two
      capillary types (small fenestrated and irregular sinusoidal capillaries) could be
      demonstrated. The presence of fenestrated capillaries together with other
      morphological features (such as accumulation of the small electron-dense granules
      at the basal pole and the presence of basolateral microvilli) near the basal
      portion of the acinar cells suggest that the Harderian gland in T. glis might
      also be involved in an endocrine function.

PMID- 12520551
TI  - Cytological evaluation of spermatogenesis and organization of the germinal
      epithelium in the male slider turtle, Trachemys scripta.
AB  - The germ cell development in the slider turtle (Trachemys scripta) testis was
      investigated by viewing the histology of the seminiferous epithelium in plastic
      sections with a light microscope. Germ cell morphologies in the slider turtle
      testis were similar to the morphologies of other vertebrate germ cell types.
      However, the slider turtle seminiferous epithelium contained germ cells that
      progress through spermatogenesis in a temporal rather than a spatial pattern,
      resulting in a single spermatogenic event that climaxed with one massive sperm
      release in November. Mature sperm then are stored within the epididymis until
      breeding commences in the following spring. The germ cell development strategy in
      the slider turtle is different from that of other amniotes and is more
      reminiscent of the developmental strategy found in the anamniotic testis. This
      temporal progression of germ cells through spermatogenesis within a tubular
      testis represents a transitional model that may be evolutionarily significant.

PMID- 12520552
TI  - Immunocytochemical and ultrastructural characterization of mammosomatotrope-,
      growth hormone-, and prolactin-cells from the gilthead sea bream (Sparus aurata
      l., Teleostei): an ontogenic study.
AB  - Growth hormone (GH), prolactin (PRL), and mammosomatotrope (MS) cells of gilthead
      sea bream, Sparus aurata, a teleost fish, were studied in specimens from hatching
      to 15 months (adults) using conventional electron microscopy and an immunogold
      method using anti-tilapia GH sera and anti-chum salmon PRL serum. MS cells,
      immunoreactive to both anti-GH sera and anti-PRL sera, had been first identified
      in fish in a previous study in newly hatched larvae and in older larvae and
      juvenile specimens of Sparus aurata by light microscopic immunocytochemistry. In
      the present work, MS cells reacted positively to immunogold label only in older
      larvae and juveniles and their secretory granules immunoreacted with both GH and
      PRL antisera or with only one of them. MS cells were ultrastructurally similar to
      the PRL cells, with which they coincided in time. This is the first report on the
      ultrastructural characterization of MS cells in fish. In adults, the secretory
      granules of GH cells (immunoreactive to anti-GH serum) were mainly round, of
      variable size, and had a homogeneous, highly electron-dense content. Irregularly
      shaped secretory granules were also present. PRL cells (immunoreactive to anti
      PRL serum) were usually observed in a follicular arrangement; they showed few,
      small, and mainly round secretory granules with a homogeneous and high or medium
      electron-dense content. Some oval or elongated secretory granules were also
      observed. GH and PRL cells that showed involutive features were also found. In
      newly hatched larvae, GH, PRL, and MS cells could not be distinguished either by
      their ultrastructure or by the immunogold labeling of the secretory granules. In
      1-day-old larvae, presumptive GH and PRL cells were observed according to their
      position in the pituitary gland. In 2-day-old larvae, a few cells showed some of
      the ultrastructural features described for GH and PRL cells of adults. During
      development, the number, size, and shape of the secretory granules in both cell
      types clearly increased and the organelles developed gradually. Some GH cells
      were found undergoing mitosis.

PMID- 12520553
TI  - Anatomy and histology of the brain and sense organs of the antarctic plunderfish
      Dolloidraco longedorsalis (Perciformes: Notothenioidei: Artedidraconidae), with
      comments on the brain morphology of other artedidraconids and closely related
      harpagiferids.
AB  - In the high-latitude shelf waters of Antarctica, fishes in the perciform suborder
      Notothenioidei dominate the fish fauna and constitute an adaptive radiation and a
      species flock. The 25 species of notothenioid plunderfishes, comprising four
      genera of the family Artedidraconidae, contribute substantially to fish species
      diversity on the high Antarctic shelf. A mental barbel is an autapomorphy for the
      family. Dolloidraco longedorsalis is the most abundant artedidraconid at depths
      over 400 m in these waters. In this article we present the anatomy and histology
      of the brain and special sense organs of Dolloidraco and compare it to the brains
      of other artedidraconids, closely related harpagiferids, and more generally to
      other notothenioids. We provide a detailed drawing of the brain and cranial
      nerves. The brain of Dolloidraco is simple, without external hypertrophy of
      sensory or motor regions, but contains several unusual features associated with
      the ventricular system and CSF, including well-developed circumventricular
      organs, subependymal expansions, and subarachnoid cisterns; and a ventricle in
      the corpus cerebellum. The brain of Dolloidraco also contains a lobed chief
      sensory nucleus of the trigeminal nerve that is correlated across species with
      barbel length. The eyes are large and contain a small choroid rete, a structure
      previously thought to be absent from members of this family. We document the
      histology of the duplex retina, olfactory apparatus, cutaneous taste buds, and
      barbel musculature and innervation. We discuss the role of pedomorphy in
      producing simplified brain morphologies. We consider the possibility that
      Dolloidraco is a somatosensory specialist-an unusual feature among vertebrates
      and decide that this is unlikely.

PMID- 12520555
TI  - Non-inferiority trials: design concepts and issues - the encounters of academic
      consultants in statistics.
AB  - Placebo-controlled trials are the ideal for evaluating medical treatment
      efficacy. They allow for control of the placebo effect and are most efficient,
      requiring the smallest numbers of patients to detect a treatment effect. A
      placebo control is ethically justified if no standard treatment exists, if the
      standard treatment has not been proven efficacious, there are no risks associated
      with delaying treatment or escape clauses are included in the protocol. Where
      possible and justified, they should be the first choice for medical treatment
      evaluation. Given the large number of proven effective treatments, placebo
      controlled trials are often unethical. In these situations active-controlled
      trials are generally appropriate. The non-inferiority trial is appropriate for
      evaluation of the efficacy of an experimental treatment versus an active control
      when it is hypothesized that the experimental treatment may not be superior to a
      proven effective treatment, but is clinically and statistically not inferior in
      effectiveness. These trials are not easy to design. An active control must be
      selected. Good historical placebo-controlled trials documenting the efficacy of
      the active control must exist. From these historical trials statistical analysis
      must be performed and clinical judgement applied in order to determine the non
      inferiority margin M and to assess assay sensitivity. The latter refers to
      establishing that the active drug would be superior to the placebo in the setting
      of the present non-inferiority trial (that is, the constancy assumption).
      Further, a putative placebo analysis of the new treatment versus the placebo
      using data from the non-inferiority trial and the historical active versus
      placebo-controlled trials is needed. Useable placebo-controlled historical trials
      for the active control are often not available, and determination of assay
      sensitivity and an appropriate M is difficult and debatable. Serious
      consideration to expansions of and alternatives to non-inferiority trials are
      needed.

PMID- 12520556
TI  - Non-inferiority trials: the 'at least as good as' criterion.
AB  - To demonstrate in a clinical trial that a new or experimental therapy (et) is 'at
      least as good as' a standard therapy (st), a statistical test or confidence
      interval procedure must rule out clinical inferiority with a high probability.
      The term 'at least as good as' implies equivalent but not necessarily superior
      efficacy. As it is statistically impossible to demonstrate equivalence (that is,
      prove the null hypothesis of no difference), Blackwelder proposed a one-sided
      significance test to reject the null hypothesis that standard therapy is better
      than experimental therapy by a clinically acceptable amount, delta(BW). In this
      paper, Blackwelder's approach is redefined in terms of the ratio of two means
      (R(True)= mu(et)/mu(st)) based on a continuous variate with higher values
      denoting greater improvement. The ratio-based equivalents to Blackwelder's
      hypotheses will be shown. The ratio parameter has the benefit of being available
      as a dimensionless percentage, not tied to a specified difference in means. Thus,
      a study can be sized to assure, with high probability, that the experimental
      therapy is 'at least' (R(LB)x100) per cent 'as effective as' the standard
      therapy, where R(LB) is the selected lower bound on the percentage effectiveness.
      A practical rationale is given for defining non-inferiority as a high fraction or
      percentage of the standard drug's efficacy, both in terms of statistical
      efficiency and medical relevance. For most typical 'at least as good as'
      applications (when R(LB)<R(True) < or =1), the ratio formatted test of
      H(0):R(True)< or =R(LB) is shown to be more efficient than Blackwelder's test of
      H(0): mu(st) - mu(et) > or = delta(BW), thereby requiring smaller sample sizes to
      detect the directionally based non-null alternatives contained in H(1):
      mu(et)/mu(st)>R(LB) or, equivalently, mu(st) - mu(et)<delta(BW). Further, when
      R(True)= 1.0, tests of Blackwelder's hypotheses, their ratio-based equivalents
      and conventional superiority can be evaluated for comparative efficiency. Testing
      H(0):R(True)< or =R(LB) with single-sided critical region of size alpha, versus
      H(1):R(True)>R(LB), is shown to be more efficient than excluding R(LB) from the
      lower limit of a 100(1-2alpha) per cent two-sided symmetric confidence interval
      centred by R. Relevant examples will be presented.

PMID- 12520557
TI  - A new test of non-inferiority for anti-infective trials.
AB  - This paper describes a new statistical test of non-inferiority in clinical trials
      of anti-infective medications. The test allows the inferiority limit, delta, to
      vary with the underlying success rates. The test is a simple modification of the
      standard fixed-delta test, and its parameters can be adjusted to yield the fixed
      delta test, a test similar to the FDA's Points-to-Consider procedure, or a test
      with nearly constant power values over a range of success rates. The test
      satisfies the size and power criteria for a valid statistical test. The effects
      on the test of lowering success rates through stringent criteria or through error
      are discussed.

PMID- 12520558
TI  - Some fundamental issues with non-inferiority testing in active controlled trials.
AB  - In an active controlled non-inferiority trial without a placebo arm, it is often
      not entirely clear what the primary objective is. In many cases the considered
      goal is to demonstrate that the experimental treatment preserves at least some
      fraction of the effect of the active control. The active control effect is a
      parameter, the value of which is unknown. To test the hypothesis of effect
      preservation, the classical confidence interval approach requires specification
      of a non-inferiority margin which is a function of the unknown active control
      effect. When the margin is estimated, it is also not clear what is the relevant
      type I error of making a false assertion about preservation of the active control
      effect. The statistical uncertainty of the estimated margin arguably needs to be
      incorporated in evaluation of the type I error. In this paper we discuss these
      fundamental issues. We show that the classical confidence interval approach
      cannot attain the target type I error exactly since this error varies as the
      sample size or as the values of the nuisance parameters in the active controlled
      trial change. In contrast, the preservation tests, as proposed in literature, can
      attain the target type I error rate exactly, regardless of the sample size and
      the values of the nuisance parameters, but can do so only at the price of several
      strong assumptions holding that may not be directly verifiable. One assumption is
      the constancy condition holding whereby the effect of the active control in the
      historical trial populations is assumed to carry to the population of the active
      control trial. When this condition is violated, both the confidence interval
      approach and the preservation test method may be problematic.

PMID- 12520559
TI  - TACT method for non-inferiority testing in active controlled trials.
AB  - In active controlled trials without a placebo arm, non-inferiority testing is
      often considered but has different objectives. For the objective of demonstrating
      the efficacy of an experimental treatment or retention of a fraction of the
      control effect by the treatment, there are two types of statistical methods for
      testing - the synthesis method and the confidence interval method. According to
      the study of Wang, Hung and Tsong, the former is efficient under the so-called
      constancy condition but may have the alpha error rate inflate rapidly if the
      condition does not hold. In contrast, the latter method with careful selection of
      the non-inferiority margin tends to be conservative if the condition holds and
      may still have a valid alpha error otherwise unless the effect of the active
      control is less to a large extent in the active controlled trial than in the
      historical trials. We developed the TACT method, Two-stage Active Control
      Testing, as a viable compromise between the two methods. Through the TACT method,
      the uninterpretable non-inferiority testing may be avoided prior to the end of
      the trial. The TACT method carefully constructed can have a valid alpha error
      rate and the power close to the synthesis method if the constancy condition
      holds. In addition, the TACT method is more powerful than the confidence interval
      method for testing for the efficacy of the new treatment relative to the putative
      placebo and for showing that the new treatment is not inferior to the active
      control comparator.

PMID- 12520560
TI  - Design and analysis of non-inferiority mortality trials in oncology.
AB  - The recent revision of the Declaration of Helsinki and the existence of many new
      therapies that affect survival or serious morbidity, and that therefore cannot be
      denied patients, have generated increased interest in active-control trials,
      particularly those intended to show equivalence or non-inferiority to the active
      control. A non-inferiority hypothesis has historically been formulated in terms
      of a fixed margin. This margin was historically designed to exclude a 'clinically
      meaningful difference', but has become recognized that the margin must also be no
      larger than the assured effect of the control in the new study. Depending on how
      this 'assured effect' is determined or estimated, the selected margin may be very
      small, leading to very large sample sizes, especially when there is an added
      requirement that a loss of some specified fraction of the assured effect must be
      ruled out. In cases where it is appropriate, this paper proposes non-inferiority
      analyses that do not involve a fixed margin, but can be described as a two
      confidence interval procedure that compares the 95 per cent two-sided CI for the
      difference between the treatment and the control to a confidence interval for the
      control effect (based on a meta-analysis of historical data comparing the control
      to placebo) that is chosen to preserve a study-wide type I error rate of about
      0.025 (similar to the usual standard for a superiority trial) for testing for
      retention of a prespecified fraction of the control effect. The approach assumes
      that the estimate of the historical active-control effect size is applicable in
      the current study. If there is reason to believe that this effect size is
      diminished (for example, improved concomitant therapies) the estimate of this
      historical effect could be reduced appropriately. The statistical methodology for
      testing this non-inferiority hypothesis is developed for a hazard ratio (rather
      than an absolute difference between treatments, because a hazard ratio seems
      likely to be less population dependent than the absolute difference). In the case
      of oncology, the hazard ratio is the usual way of comparing treatments with
      respect to time to event (time to progression or survival) endpoints. The
      proportional hazards assumption is regarded as reasonable (approximately
      holding). The testing procedures proposed are conditionally equivalent to two
      confidence interval procedures that relax the conservatism of two 95 per cent
      confidence interval testing procedures and preserve the type I error rate at a
      one-sided 0.025 level. An application of this methodology to Xeloda, a recently
      approved drug for the treatment of metastatic colorectal cancers, is illustrated.
      Other methodologies are also described and assessed - including a point estimate
      procedure, a Bayesian procedure and two delta-method confidence interval
      procedures. Published in 2003 by John Wiley & Sons, Ltd.

PMID- 12520561
TI  - Exact unconditional tests for testing non-inferiority in matched-pairs design.
AB  - The problem of testing non-inferiority in a 2 x 2 matched-pairs sample is
      considered. Two exact unconditional tests based on the standard and the
      confidence interval p-values are proposed. Although tests of non-inferiority have
      two nuisance parameters under the null hypothesis, the exact tests are defined by
      reducing the dimension of nuisance parameter space from two to one using the
      monotonicity of the distribution. The exact sizes and powers of these tests and
      the existing asymptotic test are considered. The exact tests are found to be
      accurate in view of their size property. In addition, the exact test based on the
      confidence interval p-value is more powerful than the other exact test. It is
      shown that the asymptotic test is inaccurate, that is, its size exceeds the
      claimed nominal level alpha. Therefore, it recommends a cautious approach in use
      of the asymptotic test for the problem of testing non-inferiority, particularly
      when sample sizes are small or moderately large.

PMID- 12520562
TI  - Analysis of clustered matched-pair data for a non-inferiority study design.
AB  - Hypothesis testing of matched-pair data has been adapted for equivalence (one-
      and two-sided) study designs; however, a statistical problem arises when more
      than one measurement is recorded for each study subject. Ignoring the correlation
      between the repeated measurements per subject may underestimate the standard
      error of the parameter estimate. A method of testing for non-inferiority or
      equivalence of clustered matched-pair data is not yet available. This paper
      proposes a Wald-type test statistic for a non-inferiority hypothesis and applies
      it to the comparison of two diagnostic procedures.

PMID- 12520563
TI  - Rank-based tests for non-inferiority and equivalence hypotheses in multi-centre
      clinical trials using mixed models.
AB  - Rank-based procedures for testing non-inferiority and equivalence hypotheses for
      data (continuous) arising from multi-centre clinical trials are developed using
      mixed models. The centres are presumed to be a random sample from the population
      of centres which might conceivably use the treatments under investigation, and
      the treatment effects are assumed to be fixed. It is assumed that there are no
      interactions between treatments and centres. Non-inferiority and equivalence
      hypotheses are tested using rank (R) estimators. The R-estimators are obtained by
      minimizing a combined dispersion function. The combined dispersion function is a
      sum of separate dispersion functions from each centre. Both the combined
      dispersion function and the centre-specific dispersion functions are piecewise
      linear functions. As a result, the R-estimates are expected to be less influenced
      by outliers. Large sample properties of the R-estimators including efficiencies
      are developed. A small scale simulation study is conducted to compare the
      performances (empirical levels and powers) of the non-parametric procedures and
      the normal theory based procedures.

PMID- 12520564
TI  - Application of models for multivariate mixed outcomes to medical device trials:
      coronary artery stenting.
AB  - The approval process for some medical devices involves a single-arm trial in
      which the outcomes associated with the new device are compared to the expected
      outcomes associated with approved devices, the latter denoted the objective
      performance criterion (OPC). In this paper, models for multivariate mixed
      outcomes are applied to derive the OPC for a medical device to be used in
      clinical evaluations of the same type of device. We illustrate the techniques by
      determining the OPC for coronary artery stents, metal cages used to widen blocked
      coronary arteries in patients with coronary artery disease, using data from seven
      randomized trials of stents approved for use in the U.S.A. involving 5806
      patients. The OPC is based on two 9-month endpoints: target lesion
      revascularization, a binary outcome, and proportion diameter stenosis, a
      continuous outcome. To account for the correlation between mixed outcomes we
      consider factorization of the likelihood into marginal and conditional
      components, or adoption of a latent variable model. Because the models have
      different structural forms, standard methods for model comparison (such as the
      AIC and BIC) cannot be used. We discuss how model identifiability and valid
      inference are achieved, and then adapt the deviance information criterion (DIC)
      and the pseudo-Bayes factor (PSBF) to select the best model. Nine months post
      stenting, we find that the average posterior probability (standard deviation) of
      target lesion revascularization ranges from 0.086 (0.008) for non-diabetics with
      one diseased vessel to 0.163 (0.022) for diabetics with three diseased vessels.
      When considering proportion diameter stenosis, the corresponding posterior means
      are 0.375 (0.020) and 0.427 (0.030). The correlation coefficient of the
      components of the OPC lies in the range 0.042 to 0.116.

PMID- 12520566
TI  - Pre-emptive surgery and increasing demands for technical perfection.

PMID- 12520567
TI  - Effect on diagnostic efficiency of analgesia for undifferentiated abdominal pain.
AB  - BACKGROUND: The question of whether it is safe to provide analgesia for patients
      with undifferentiated acute abdominal pain is marked by longstanding controversy
      over the possible masking of physical findings. The goal of this review is to
      assess the pertinent studies. METHOD: A Medline search was performed in April
      2002, using the terms 'analgesia', 'abdominal pain', 'acute abdomen' and
      'morphine'. Other articles were identified using the bibliographies of papers
      found through Medline. All articles reporting clinical trials of analgesia and
      its effects on diagnosis or physical examination were reviewed. RESULTS: A total
      of eight trials (one reported only as an abstract) were identified. Because of
      significant disparity in trial design, no formal analysis such as meta-analysis
      was performed. However, detailed review of the trials revealed a striking
      consistency in results. In no study was there an association between analgesia
      and diagnostic impairment or dangerous masking of the findings of physical
      examination. CONCLUSION: The literature addressing early pain relief for
      abdominal pain is characterized by weaknesses, but there is a common theme
      suggesting that analgesia is safe. Pending further research, which should address
      some of the shortcomings of extant studies, a practice of judicious provision of
      analgesia appears safe, reasonable and in the best interests of patients in pain.

PMID- 12520568
TI  - Surgeons and cognitive processes.
AB  - BACKGROUND: The surgical mind is geared to make important decisions and perform
      highly skilled tasks. The aim of this review is to explore the cognitive
      processes that link these actions. METHODS: The core of this review is derived
      from a literature search of a computer database (Medline). RESULTS AND
      CONCLUSION: The surgical image is one of action. However, the effective
      performance of surgery requires more than mere manual dexterity and it is evident
      that competent surgeons exhibit the cognitive traits that are held by all
      experts. The changes that are occurring in surgery indicate a need to place
      greater emphasis on the cognitive processes that underpin the practice of
      surgery. It is important that surgeons do not become victims of their own cult
      image.

PMID- 12520569
TI  - Prospective randomized study of steroids in the prevention of ischaemic injury
      during hepatic resection with pedicle clamping.
AB  - BACKGROUND: The major drawback of hepatic pedicle clamping is ischaemia
      reperfusion injury with impairment of liver function. Perioperative steroid
      administration has been advocated to reduce liver damage. The aim of this
      prospective, randomized study was to determine whether steroid administration can
      reduce liver injury and improve short-term outcome. METHODS: Fifty-three patients
      undergoing liver resection were randomized to a steroid group (group 1) or to a
      control group (group 2); patients in group 1 received methylprednisolone 30 mg/kg
      30 min before liver resection whereas those in group 2 did not. Serum levels of
      interleukin (IL) 6, total bilirubin, aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT), and prothrombin time (PT) were measured. Length of stay,
      and type and number of complications were recorded. RESULTS: Serum IL-6 levels
      were significantly lower in the steroid group than in the control group 24 h
      after surgery. Steroid administration significantly modified AST, ALT and PT
      levels only in patients with chronic liver disease. Overall and lung-related
      morbidity were not significantly different between the two groups. CONCLUSIONS:
      Steroid administration suppresses serum IL-6 levels, but has no effect on short
      term outcome.

PMID- 12520570
TI  - Autologous blood storage before hepatectomy for hepatocellular carcinoma with
      underlying liver disease.
AB  - BACKGROUND: Preoperative autologous blood donation has been suggested for
      patients with liver disease who are to undergo liver resection. The aim of this
      retrospective study was to clarify the risk factors for increased blood loss and
      the need for blood transfusion during hepatectomy for hepatocellular carcinoma
      (HCC). METHODS: From January 1996 to December 2000, 206 consecutive patients,
      98.5 per cent of whom had underlying liver disease, underwent elective
      hepatectomy for HCC. RESULTS: Major hepatectomy was performed in 34 patients
      (16.5 per cent) and minor hepatectomy in 172 patients (83.5 per cent). The mean
      blood loss was 410 (median 260) ml. Eleven (5.3 per cent) of the 206 patients
      received blood transfusion during or after the operation. Operation time (P =
      0.004) and central venous pressure (CVP) (P = 0.041) were independently
      correlated with blood loss of more than 1000 ml. Only preoperative haemoglobin
      level (P = 0.001) was independently correlated with the need for blood
      transfusion. CONCLUSION: In patients with underlying liver disease, maintaining
      CVP at a level below 5 cm H2O during parenchymal transection to reduce blood loss
      is more important than reserving autologous blood before the operation.

PMID- 12520571
TI  - Organ-preserving pancreatic head resection in chronic pancreatitis.
AB  - BACKGROUND: Twenty to thirty per cent of patients with chronic pancreatitis
      develop inflammatory enlargement of the head of the pancreas. A safe procedure
      has been developed for duodenum-preserving pancreatic head resection; this report
      describes the preliminary results achieved. METHODS: Thirty patients, 27 men and
      three women of mean age 44 years, underwent surgical resection following the
      development of an inflammatory mass in the pancreatic head. All patients had
      weight loss and frequent abdominal pain. Jaundice was present in three and
      diabetes mellitus in ten patients. The diagnosis of chronic pancreatitis was made
      by a combination of endoscopic retrograde cholangiopancreatography, sonography
      and computed tomography. Pancreatic function was assessed by amylum tolerance
      test (ATT), oral glucose tolerance test and stool elastase measurement. The
      surgical procedure involved wide local resection of the inflammatory tumour in
      the pancreatic head, without division of the pancreas over the portal vein.
      Reconstruction involved drainage via a jejunal Roux-en-Y loop. In three icteric
      cases, prepapillary bile duct anastomosis was also performed using the same
      jejunal loop. RESULTS: There were no hospital deaths or major complications.
      After a median follow-up of 10 (range 6-14) months, all patients were symptom
      free. The mean increase in body-weight was 8.9 (range 4-20) kg. The ATT and stool
      elastase level demonstrated improved exocrine function but there was no change in
      endocrine function. CONCLUSION: This type of pancreatic head resection is a safe
      procedure that provides good short-term relief of symptoms associated with
      inflammatory changes in the head of the pancreas in chronic pancreatitis.

PMID- 12520572
TI  - Risk factors for perioperative morbidity and mortality after extended hepatectomy
      for hepatocellular carcinoma.
AB  - BACKGROUND: Extended hepatectomy with resection of more than four segments is a
      high-risk operation, especially in patients with hepatocellular carcinoma (HCC)
      associated with chronic liver disease. This study evaluated the risk factors for
      morbidity and mortality following extended hepatectomy for HCC. METHODS:
      Preoperative and intraoperative variables of 155 patients who underwent extended
      hepatectomy for HCC were analysed to identify risk factors for postoperative
      morbidity and mortality. RESULTS: The overall morbidity rate was 55.5 per cent (n
      = 86). Most morbidity was due to ascites or pleural effusion. Significant life
      threatening complications occurred in 20.0 per cent (n = 31). The perioperative
      mortality rate was 8.4 per cent (n = 13). Multivariate analysis found that portal
      clamping (P = 0.023) and perioperative blood transfusion (P < 0.001) were risk
      factors for morbidity, whereas perioperative blood transfusion (P < 0.001) was
      the only risk factor for significant morbidity. Co-morbid illness (P = 0.019) and
      perioperative blood transfusion (P = 0.004) were risk factors for perioperative
      mortality. CONCLUSION: Meticulous operative techniques to minimize blood loss and
      transfusion, while avoiding a prolonged Pringle manoeuvre, may help reduce
      postoperative morbidity. Avoidance of perioperative blood transfusion and careful
      preoperative selection of patients in terms of overall physiological status are
      important measures to reduce the postoperative mortality rate.

PMID- 12520573
TI  - The value of magnetic resonance cholangiopancreatography in predicting common
      bile duct stones in patients with gallstone disease.
AB  - BACKGROUND: The application of available predictive scoring systems for the
      detection of common bile duct (CBD) stones has not reduced the number of patients
      who undergo unnecessary endoscopic retrograde cholangiopancreatography. The aim
      of this study was to create a predictive model for CBD stones and to assess the
      value of magnetic resonance cholangiopancreatography (MRCP) in prediction.
      METHODS: In 1998, 366 patients with gallstone disease (118 males, 248 females;
      mean age 57 (range 8-84) years) underwent cholecystectomy. Statistical analysis
      was performed on patient data obtained at the time of first presentation.
      RESULTS: CBD stones were demonstrated in 43 (12 per cent) of 366 patients. The
      predictive model for common duct stones included ultrasonography showing CBD
      stones or bile duct dilatation, age greater than 60 years, fever, serum alkaline
      phosphatase level above 670 units/l and serum amylase level above 95 units/l. In
      patients with a predicted probability greater than 5 per cent, CBD stones were
      present in 11 per cent, compared with 1 per cent in patients with a probability
      of 5 per cent or less. MRCP had an observed sensitivity of 95 per cent,
      specificity of 100 per cent, positive predictive value of 100 per cent and
      negative predictive value of 98 per cent. CONCLUSION: In patients with a
      predicted probability for CBD stones of more than 5 per cent, MRCP is recommended
      in order to confirm the presence or absence of stones and as guidance in further
      management.

PMID- 12520574
TI  - Right lobe living donor liver transplantation with or without venovenous bypass.
AB  - BACKGROUND: Venovenous bypass was considered necessary to maintain haemodynamic
      stability and avoid splanchnic and retroperitoneal congestion during the
      anhepatic phase of liver transplantation. It was essential for right lobe living
      donor liver transplantation (LDLT) in which the inferior vena cava needed to be
      cross-clamped to construct wide and short hepatic vein anastomoses. However, many
      complications related to venovenous bypass have been reported. This study aimed
      to determine whether venovenous bypass was necessary for right lobe LDLT.
      METHODS: Between June 1996 and June 2001, 72 patients underwent right lobe LDLT.
      The outcomes for the first 29 patients who had venovenous bypass during the
      operation were compared with those of the remaining 43 patients who did not have
      venovenous bypass. In patients without bypass, blood pressure was maintained
      during the anhepatic phase by boluses of fluid infusion and vasopressors.
      RESULTS: Compared with patients undergoing operation without venovenous bypass,
      patients who had venovenous bypass required significantly more blood, fresh
      frozen plasma and platelet infusion, and had a lower body temperature; their
      postoperative hepatic and renal function in the first week was worse than that in
      patients who did not have a bypass. The time to tracheal extubation was longer
      and the incidence of reintubation for ventilatory support was higher with
      venovenous bypass. Six of the 29 patients with venovenous bypass died in
      hospital, compared with two of the 43 patients without a bypass (P = 0.05). By
      multivariate analysis, the lowest body temperature during the transplant
      operation was the most significant factor that determined hospital death.
      CONCLUSION: Venovenous bypass is not necessary and is probably harmful to
      patients undergoing right lobe LDLT, and should therefore be avoided.

PMID- 12520575
TI  - Radial artery as a conduit for diabetic crural bypass.

PMID- 12520576
TI  - Mortality, morbidity and functional outcome after ileorectal anastomosis.
AB  - BACKGROUND: Total colectomy with an ileorectal anastomosis (IRA) is a commonly
      performed operation. Postoperative mortality and morbidity are reported to be low
      and functional outcome is generally rated as good to excellent. The aim of this
      study was to review postoperative mortality, morbidity and functional results in
      an effort to identify risk factors predictive of a poor outcome. METHODS: Some
      215 patients (118 women and 97 men) with a median age of 33 (interquartile range
      (i.q.r.) 25-47) years underwent an IRA between November 1990 and December 1999.
      Median follow-up was 2 years 9 months (i.q.r. 1-5 years). The clinical notes of
      these patients were reviewed retrospectively to analyse the postoperative course,
      bowel function and long-term clinical outcome. RESULTS: The indications for
      surgery included familial adenomatous polyposis (52.1 per cent), Crohn's disease
      (14.4 per cent), functional bowel disorder (14.4 per cent), ulcerative colitis
      (8.4 per cent) and colonic carcinoma (4.7 per cent). The overall 30-day mortality
      and morbidity rates were 0.9 and 26.0 per cent respectively. This included
      anastomotic leak (6.5 per cent), small bowel obstruction (14.4 per cent), fistula
      (2.8 per cent) and anastomotic stricture (1.4 per cent). The incidence of fistula
      and anastomotic stricture was significantly higher in Crohn's disease (P < 0.001
      and P = 0.005 respectively). Only 16 of 31 patients with Crohn's disease had a
      functioning IRA at long-term follow-up. Median stool frequency was 3 (i.q.r. 3-5)
      per day one year following surgery and did not change with longer follow-up.
      CONCLUSION: Mortality and morbidity rates following IRA are low. Postoperative
      fistula and anastomotic stricture are more common in patients with Crohn's
      disease, approximately half of whom will eventually need a permanent ileostomy.
      Long-term bowel function for all groups is satisfactory.

PMID- 12520577
TI  - Effect of antiadhesive agents on peritoneal carcinomatosis in an experimental
      model.
AB  - BACKGROUND: Auto-crosslinked polysaccharide hyaluronan-based solution
      (Hyalobarrier-gel) prevents postoperative adhesions. However, its effect on
      tumour growth is still unknown. The aim of the present study was therefore to
      investigate the impact on survival of intra-abdominally administered Hyalobarrier
      gel, native hyaluronan (HA) and hyaluronan/carboxymethylcellulose (HA/CMC), after
      intraperitoneal tumour implantation. METHODS: After receiving an intraperitoneal
      inoculum of the human HT29 colorectal cell line, 615 athymic nude mice were
      assigned randomly to five groups: groups 1 and 2 received Hyalobarrier-gel 20
      mg/ml (n = 124) and 40 mg/ml (n = 126) respectively; groups 3 and 4 received HA
      (n = 120) and HA/CMC film (Seprafilm) (n = 123) respectively. The survival of
      each treated group was compared with that of group 5, the control, which had no
      treatment (n = 122). RESULTS: As 34 of the 615 mice were not eligible, 581
      animals were considered for the analysis. At 120 days, 136 animals (23.4 per
      cent) were still alive. At autopsy there was macroscopic absence of tumour in 75
      cases (12.9 per cent). No statistically significant differences were found
      between the treatment and the control groups with respect to postoperative death
      and absence of tumour implantation. There was no difference in survival rate
      between the control group and groups treated with Hyalobarrier-gel, HA or HA/CMC.
      CONCLUSION: Hyalobarrier-gel, HA and HA/CMC had no negative impact on the
      survival rate in mice that received an intraperitoneal implantation of HT29
      colorectal human tumour cells.

PMID- 12520578
TI  - Risk of dysplasia in the columnar cuff after stapled restorative proctocolectomy.
AB  - BACKGROUND: Stapled restorative proctocolectomy (SRP) for ulcerative colitis
      retains a 'cuff' of columnar epithelium, which carries a risk of undergoing
      malignant change. The risk of neoplastic transformation was studied in a series
      of patients who underwent SRP for ulcerative colitis. METHODS: One hundred and
      thirty-five patients who underwent SRP for ulcerative colitis between 1988 and
      1998 were followed up by cuff surveillance biopsy. The median follow-up was 56
      (range 12-145) months and the median time since diagnosis of ulcerative colitis
      was 8.8 (range 2-32) years. RESULTS: The cuff biopsies showed no dysplasia or
      carcinoma. The accuracy of obtaining cuff mucosa in the biopsy was 65 per cent.
      Chronic inflammation was present in 94 per cent of cuff biopsies. CONCLUSION:
      This study shows no evidence of either dysplasia or carcinoma in the columnar
      cuff mucosa, up to 12 years after pouch formation. This suggests that cuff
      surveillance in the first decade after SRP, in the absence of dysplasia or
      carcinoma in the original colectomy specimen, may be unnecessary. Regular cuff
      surveillance biopsies after SRP should continue for patients with high-grade
      dysplasia or carcinoma in the original resection specimen.

PMID- 12520579
TI  - Lymphoedema and reduced shoulder function as indicators of quality of life after
      axillary lymph node dissection for invasive breast cancer.
AB  - BACKGROUND: The aim was to explore measurements of arm circumference and shoulder
      abduction as indicators of quality of life after axillary lymph node dissection
      for invasive breast cancer. METHODS: Differences in arm circumference and
      shoulder abduction were measured in 465 consecutive women who underwent axillary
      lymph node dissection. These women received a treatment-specific questionnaire on
      the severity of physical disability and the effects on their daily life and well
      being. RESULTS: The questionnaire was returned by 400 women (86 per cent). Of
      these 400, only the 332 women who did not receive axillary radiotherapy were
      included in the analysis. Their mean time since axillary lymph node dissection
      was 4.2 (range 0.3-28) years. For 86 patients (26 per cent) there was a
      difference in arm circumference of 2 cm or more, or a difference in abduction of
      20 degrees or more. These patients found it more difficult to do household
      chores, were more likely to have given up hobbies, felt more disabled and were
      more likely to be treated by a physiotherapist. However, complaints also occurred
      among the women with smaller differences in arm circumference and shoulder
      abduction, although the frequency and severity of their complaints were similar
      to those in women without swelling of the arm or without restricted shoulder
      abduction. CONCLUSION: Measuring arm circumference and shoulder abduction during
      control visits identifies only some of the women whose daily life and well-being
      is affected by the side-effects of axillary lymph node dissection.

PMID- 12520580
TI  - The National Health Service Breast Screening Programme and British Association of
      Surgical Oncology audit of quality assurance in breast screening 1996-2001.
AB  - BACKGROUND: The National Health Service Breast Screening Programme (NHSBSP) is an
      example of a nationally coordinated quality assurance programme in which all the
      professional groups involved participate. METHODS: Surgeons, radiologists and
      pathologists defined the clinical outcome measures against which they would
      subsequently be audited. The NHSBSP and the Association of Breast Surgery at BASO
      are jointly responsible for coordinating an annual audit of all surgical
      activities undertaken within the NHSBSP. RESULTS: The trends for key outcome
      measures between 1996 and 2001 are provided. The preoperative diagnosis rate
      (minimum standard 70 per cent or more) improved from 63 to 87 per cent. This rise
      was mirrored by an increase in the use of core biopsy in preference to fine
      needle cytology. The proportion of patients in whom lymph node status was
      recorded improved from 81 to 93 per cent. There was no significant change in the
      number of women treated by low case-load surgeons and waiting times for surgery
      increased through the study interval. CONCLUSION: The BASO-NHSBSP Breast Audit
      has recorded major changes in clinical practice over 5 years. A key feature has
      been the dissemination of good practice through feedback of the results at local
      and national level.

PMID- 12520581
TI  - Current practice of emergency vagotomy and Helicobacter pylori eradication for
      complicated peptic ulcer in the United Kingdom.
AB  - BACKGROUND: The aim was to assess the current opinion of surgeons, by
      subspecialty, towards vagotomy and the practice of Helicobacter pylori testing,
      treatment and follow-up, in patients with bleeding or perforated duodenal ulcer.
      METHODS: A postal questionnaire was sent to 1073 Fellows of the Association of
      Surgeons of Great Britain and Ireland in 2001. RESULTS: Some 697 valid
      questionnaires were analysed (65.0 per cent). Most surgeons did not perform
      vagotomy for perforated or bleeding duodenal ulcer. There was no statistical
      difference between the responses of upper gastrointestinal surgeons and those of
      other specialists for perforated (P = 0.35) and bleeding (P = 0.45) ulcers.
      Respondents were more likely to perform a vagotomy for bleeding than for a
      perforated ulcer (P < 0.001). Although more than 80 per cent of surgeons
      prescribed H. pylori eradication treatment after operation, fewer than 60 per
      cent routinely tested patients for H. pylori eradication. Upper gastrointestinal
      surgeons were more likely to prescribe H. pylori treatment and test for
      eradication than other specialists (P < 0.01). CONCLUSION: Most surgeons in the
      UK no longer perform vagotomy for duodenal ulcer complications.

PMID- 12520582
TI  - Impact of surgical procedure for gastric cancer on quality of life.
AB  - BACKGROUND: The aim was to assess quality of life in a group of patients who had
      a curative resection for gastric cancer. METHODS: The European Organization for
      Research and Treatment of Cancer QLQ-C30 questionnaire with a gastric cancer
      specific module was used in patients who had undergone R0 gastrectomy between
      1992 and 1999, and who had no disease at the last check-up. A response was
      obtained from 54 patients, 36 men and 18 women, of mean age 67 years. Of these,
      24 patients had total gastrectomy and 26 D2 lymphadenectomy. RESULTS: Significant
      differences were found only in the social domain of quality of life in patients
      aged over 70 years (P = 0.036); there was no impact of operation type on overall
      quality of life. CONCLUSION: The quality of life of patients undergoing curative
      surgery for gastric cancer, regardless of age, was not significantly influenced
      by the type of gastrectomy, or whether lymphadenectomy was performed.

PMID- 12520583
TI  - Combined evaluation of mucin antigen and E-cadherin expression may help select
      patients with gastric cancer suitable for minimally invasive therapy.
AB  - BACKGROUND: MUC1 mucin is known to be highly expressed in carcinomas that show
      invasive growth and poor prognosis. Impairment of adhesion molecule E-cadherin
      expression has been widely accepted as a critical event for cancer invasion and
      metastasis. The present study evaluated the combination of mucin and E-cadherin
      status as a possible predictor of patients suitable for minimally invasive
      therapy for gastric cancer. METHODS: Two hundred and nine paraffin-embedded
      specimens of gastric carcinoma (141 early, 68 advanced) were examined by
      immunohistochemical staining using monoclonal antibodies against MUC1 mucin (MUC
      1-CORE, DF3), MUC2 mucin (Ccp58) and E-cadherin (anti-E-cad). RESULTS: Gastric
      carcinoma with MUC1-positive expression demonstrated malignant characteristics.
      Normal E-cadherin expression showed an inverse correlation with MUC1 expression.
      Patients with early gastric carcinoma who had a combination of normal E-cadherin
      and MUC1-negative expression had no recurrence and a favourable prognosis.
      Moreover, cancers with normal E-cadherin/MUC1-negative expression were not found
      at an advanced stage in differentiated-type carcinoma. CONCLUSION: A normal E
      cadherin/MUC1-negative expression pattern in gastric cancer is a favourable
      marker. Preoperative estimation of the E-cadherin and MUC1 status of an
      endoscopic biopsy specimen may help select appropriate patients for minimally
      invasive treatment of gastric cancer.

PMID- 12520584
TI  - Major amputation for soft-tissue sarcoma.
AB  - BACKGROUND: Advances in oncological practice have reduced the number of major
      amputations performed for soft-tissue sarcoma, but this remains a valuable, if
      infrequent, option for both curative and palliative indications. METHODS: A
      review of patients and case-notes was carried out from the prospective sarcoma
      database at the Royal Marsden Hospital. RESULTS: Over a 10-year interval, 40
      major amputations (18 forequarter, 17 hindquarter and five through hip) were
      performed, predominantly for disease recurring after previous limb-conserving
      surgery (31 of 40). A wide variety of soft-tissue sarcoma subtypes was seen; they
      were often large (more than 10 cm; 18 of 40) or multifocal (six), usually high
      grade (25), and frequently proximal or involving neurovascular structures such
      that limb salvage was precluded. Median range age of the patients was 59 (17-87)
      years. The operative 30-day mortality rate was zero. Hospital stay was a median
      of 10.5 days for forequarter amputation, and 19 days for hindquarter and through
      hip amputation. Local recurrence occurred in ten patients, six of whom had
      concurrent distant metastases. Twenty-seven patients were alive (20 disease free)
      at a median follow-up of 12 months, nine of whom were alive without evidence of
      disease beyond 2 years. Ten patients died after a median of 7.5 months; three
      survived more than 2 years. CONCLUSION: Major amputation is a useful procedure in
      carefully selected patients with soft-tissue sarcoma.

PMID- 12520585
TI  - A comparison of video-assisted thoracoscopic oesophagectomy and radical lymph
      node dissection for squamous cell cancer of the oesophagus with open operation.
AB  - BACKGROUND: A direct comparison of open operation and video-assisted
      thoracoscopic surgery (VATS) for radical oesophagectomy has yet to be published.
      METHODS: Medical records of 149 patients with oesophageal squamous cell carcinoma
      who underwent oesophagectomy and three-field lymphadenectomy were reviewed.
      Seventy-seven patients had the thoracic procedure performed via a 5-cm
      minithoracotomy and four ports (VATS group); the others were operated on by
      conventional posterolateral thoracotomy (open group). RESULTS: The mean number of
      retrieved mediastinal nodes, blood loss and morbidity were similar in the VATS
      and open groups (33.9 versus 32.8 nodes, 284 versus 310 g, and 32 versus 38 per
      cent respectively). The thoracic procedure took longer in patients having VATS
      than in the control group (227 versus 186 min; P = 0.031). Vital capacity
      reduction was less with VATS than in the open group (15 versus 22 per cent; P =
      0.016). The 3- and 5-year survival rates were similar: 70 and 55 per cent
      respectively for VATS compared with 60 and 57 per cent for the open procedure.
      CONCLUSION: VATS provides comparable results to open radical oesophagectomy, with
      less surgical trauma.

PMID- 12520586
TI  - Individual inflammatory response of human blood monocytes to mesh biomaterials.
AB  - BACKGROUND: Alloplastic implants such as those employed in hernia repair induce
      distinct local inflammation and seroma production. As monocytes take a key
      position in the inflammatory foreign body reaction, their specific release of
      cytokines was investigated in vitro after incubation with alloplastic materials.
      METHODS: Human blood monocytes were isolated from buffy coats of 42 healthy blood
      donors. Cells were cultivated in polystyrene culture wells (4 x 10(6) cells/well)
      on polypropylene-polyglactin mesh, on polytetrafluoroethylene, in control wells
      with the addition of 1 micro g lipopolysaccharide (LPS) and on pure polystyrene.
      Supernatant was taken after 1 h and 5 days, and concentrations of tumour necrosis
      factor (TNF) alpha, interleukin (IL) 6 and IL-10 were determined. Donors were
      defined as 'high' or 'low' responders when concentrations of TNF-alpha were above
      the 75th or below the 25th percentiles, respectively. RESULTS: In contact with
      biomaterials, the monocytes liberated TNF-alpha, IL-6 and IL-10, similar to
      levels observed after stimulation with LPS. Median cytokine concentrations were
      not normally distributed and were influenced by donor, timepoint and applied
      stimulus. One donor matched the criteria for low responder and three for high
      responder. CONCLUSION: The individual was identified as an independent factor for
      the inflammatory response of monocytes to biomaterials. Moreover, high and low
      responders could be identified. The variability of cytokine release and the lack
      of a normal distribution suggest that a larger sample size should be used in
      future studies of cellular response.

PMID- 12520587
TI  - Complications and functional outcome following artificial anal sphincter
      implantation (Br J Surg 2002; 89: 877-881).

PMID- 12520588
TI  - Adjuvant therapy for rectal cancer cannot be based on the results of other
      surgeons (Br J Surg 2002; 89: 946-947).

PMID- 12520590
TI  - Experimental study of large-volume microwave ablation in the liver (Br J Surg
      2002; 89: 1003-1007).

PMID- 12520591
TI  - Letter 1: Randomized clinical trial of specific lactobacillus and fibre
      supplement to early enteral nutrition in patients with acute pancreatitis (Br J
      Surg 2002; 89: 1103-1107).

PMID- 12520592
TI  - Randomized clinical trial comparing quality of life after straight and pouch
      coloanal reconstruction (Br J Surg 2002; 89: 1108-1117).

PMID- 12520593
TI  - Letter 2: Randomized clinical trial of specific lactobacillus and fibre
      supplement to early enteral nutrition in patients with acute pancreatitis (Br J
      Surg 2002; 89: 1103-1107).

PMID- 12520595
TI  - [Measles return].

PMID- 12520596
TI  - Topical anaesthesia for small incision cataract surgery.

PMID- 12520597
TI  - Why viscoadaptives? Are they really new?

PMID- 12520599
TI  - The Staar Wave.

PMID- 12520598
TI  - Comparison of four viscoelastic substances for cataract surgery in eyes with
      cornea guttata.

PMID- 12520600
TI  - Phacotmesis.

PMID- 12520601
TI  - Tilt and tumble phacoemulsification.

PMID- 12520602
TI  - Phacoemulsification in the anterior chamber: preliminary results.

PMID- 12520603
TI  - Phaco chop: making the transition.

PMID- 12520604
TI  - Ultrasound-assisted phaco aspiration.

PMID- 12520605
TI  - Management of the mature cataract.

PMID- 12520606
TI  - Phacoemulsification in the vitreous cavity.

PMID- 12520607
TI  - Capsular tension ring as adjuvant in phacoemulsification surgery.

PMID- 12520608
TI  - Optical coherence biometry.

PMID- 12520609
TI  - Optical biometry in cataract surgery.

PMID- 12520610
TI  - White-to-white corneal diameter measurements using the eyemetrics program of the
      Orbscan topography system.

PMID- 12520611
TI  - Injector systems for foldable intraocular lens implantation.

PMID- 12520612
TI  - Incisions for implantation of foldable intraocular lenses. Development of a new
      caliper, measurement of incision sizes, and wound morphology of the cornea.

PMID- 12520613
TI  - Scheimpflug imaging of modern foldable high-refractive silicone and hydrophobic
      acrylic intraocular lenses.

PMID- 12520614
TI  - Does the PCO preventing square edge concept apply to acrylic-hydrophilic
      intraocular lenses?

PMID- 12520615
TI  - Posterior capsule opacification after implantation of polyfluorocarbon-coated
      intraocular lenses: a long-term follow-up.

PMID- 12520616
TI  - Piggyback intraocular lens implantation.

PMID- 12520617
TI  - Multifocal intraocular lenses.

PMID- 12520618
TI  - Medicare and the November elections.

PMID- 12520619
TI  - Drug seeking patients: a prescription for problems.

PMID- 12520620
TI  - The perfect prescription for Iowa's health insurance market: competition.

PMID- 12520621
TI  - Antitrust enforcers cast a wary eye on health care--AMA admonition: pay attention
      to health plans!

PMID- 12520622
TI  - Famotidine disposition in children and adolescents with chronic renal
      insufficiency.
AB  - The pharmacokinetics of intravenous famotidine (0.5 mg/kg, maximum 20 mg) were
      evaluated in 18 pediatric patients (ages 1-18 years) with stable, chronic renal
      insufficiency. Subjects were stratified by calculated creatinine clearance (Clcr)
      into mild (Clcr > or = 50 to < 90 mL/min/1.73 m2), moderate (Clcr > or = 25 to <
      50 mL/min/1.73 m2), and severe (Clcr < or = 10 mL/min/1.73 m2) renal
      insufficiency groups. Significant differences between the mild, moderate, and
      severe groups were found for elimination rate (Kel), apparent elimination half
      life (t1/2), area under the curve (AUC), and total plasma clearance (Clp) (p <
      0.01). Famotidine renal clearance (Clr) was found to be significantly different
      between the mild and severe groups (p < 0.05). A linear relationship was observed
      between Clcr and Clp (p < 0.0001; R2 = 0.70). No significant differences in
      nonrenal clearance (Clnr) were found between groups; however, Clnr as a
      percentage of Clp was significantly different in the severe group (92.9% +/- 7.3%
      Clnr) compared to the combined mild and moderate groups (21.9% +/- 45.6% Clnr) (p
      < 0.05). It was concluded that the pharmacokinetics of famotidine are
      significantly altered in children with chronic renal insufficiency; accordingly,
      dosing should be based on glomerular filtration rate (i.e., Clcr).

PMID- 12520623
TI  - Influence of mild liver impairment on the pharmacokinetics and metabolism of
      bosentan, a dual endothelin receptor antagonist.
AB  - The purpose of the study was to investigate the effect of mild liver impairment
      on the pharmacokinetics and metabolism of bosentan. Eight patients with mild
      liver impairment and 8 matching healthy subjects were treated with single and
      multiple oral 125-mg doses of bosentan. The pharmacokinetic parameters of
      bosentan and its metabolites were similar in both groups: geometric means for
      Cmax and AUC for bosentan were 2534 and 1980 ng/ml and 11,957 and 10,781 ng.h/ml
      after single doses and were 1831 and 1715 ng/ml and 7216 and 7838 ng.h/ml after
      multiple doses, respectively, in healthy subjects and patients. In both groups,
      the exposure to the metabolites was low when compared to that to bosentan. The
      decrease in exposure to bosentan after multiple dosing, indicative of
      autoinduction, tended to be less pronounced in patients as compared to healthy
      subjects. Bosentan was well tolerated in this study. In conclusion, the
      pharmacokinetics, metabolism, and tolerability of bosentan are similar in healthy
      subjects and patients with mild liver impairment.

PMID- 12520624
TI  - Pharmacokinetics of repaglinide in healthy caucasian and Japanese subjects.
AB  - The objective of this study was to investigate the pharmacokinetics of three
      different single doses (0.5, 1.0, and 2.0 mg) of repaglinide in healthy Caucasian
      and Japanese subjects. In this single-center, open-label, randomized, three
      period crossover study, 27 healthy male subjects (15 Caucasian and 12 Japanese)
      each received three different single doses of repaglinide (0.5, 1.0, and 2.0 mg)
      at consecutive 24-hour intervals. Pharmacokinetic profiles, including area under
      the curve (AUC0-t), maximum serum concentration (Cmax), time to Cmax (tmax), and
      half-life (t1/2), were determined for each dose of repaglinide. The relative
      change in blood glucose level (RC1h) and area under the blood glucose curve
      (AUGC0-1) at 1 hour after dose were also measured. After oral dosing, both Cmax
      and AUC0-t increased linearly with dose within the 0.5- to 2.0-mg dose range,
      regardless of ethnic group. Both Cmax and AUC0-t were significantly higher in
      Japanese subjects than in Caucasian subjects. At each dose of repaglinide, Cmax
      and AUC were statistically significantly higher in Japanese than in Caucasian
      subjects (p = 0.0038 and 0.023, respectively). Discrepancies in body weight and
      body mass index (BMI) between Caucasian and Japanese subjects could not explain
      the between-group differences in Cmax or AUC0-t. Statistically significant
      differences in pharmacodynamic parameters (RC1h and AUGC0-1) were found between
      ethnic groups (p < 0.0001), the difference being more pronounced for RC1h than
      AUGC0-1. At a dose of 2.0 mg, the mean decrease in RC1h was 41% for Japanese
      subjects and 24% for Caucasian subjects. Hypoglycemic reactions were more common
      at the highest dose (2.0 mg), where they were observed more frequently in
      Japanese (7 cases) than in Caucasian subjects (4 cases). It was concluded that
      higher serum levels of repaglinide and greater reductions in blood glucose levels
      are found in Japanese than in Caucasian subjects following a single oral dose of
      repaglinide within the 0.5- to 2.0-mg dose range. Repaglinide is well tolerated
      in both ethnic groups. The results indicate that glycemic control targets may be
      achieved at lower doses within the recommended range (0.5-4.0 mg/meal) when
      repaglinide is used to treat Japanese patients in comparison to Caucasian
      patients.

PMID- 12520625
TI  - Single- and multiple-dose pharmacokinetics of oral creatine.
AB  - Supplementation with exogenous creatine (Cr) has shown physiological benefits in
      humans, but little is known about the pharmacokinetics of Cr in humans. Six
      healthy males completed an open-label study consisting of a full pharmacokinetic
      analysis following a single oral dose of Cr monohydrate (71 mg kg-1) and at
      steady-state after 6 days of Cr administration (71 mg kg-1 qid). After the single
      oral dose, the clearance (CL/F) was 0.20 +/- 0.066 L h-1 kg-1, tmax was 1.9 +/-
      0.88 hours, and Cmax = 102.1 +/- 11.2 mg h L-1. At steady-state, CL/F decreased
      to 0.12 +/- 0.016 L h-1 kg-1, tmax did not change, and Cmax increased to 162.2 +/
      30.0 mg L-1. Penetration (AUCMUSCLE/AUCPLASMA) of Cr into the interstitial
      muscle space, as determined by microdialysis, was 0.47 +/- 0.09 and 0.37 +/- 0.27
      for the single dose and at steady-state, respectively. Plasma and muscle data
      were simultaneously fitted with a model incorporating a saturable absorption and
      first-order elimination process. In conclusion, repeated dosing of Cr caused a
      reduction in clearance that could result from saturation of the skeletal muscle
      pool of Cr.

PMID- 12520626
TI  - Pharmacokinetics of cyclosporine pre- and post-liver transplantation.
AB  - Cyclosporine (CyA) is an immunosuppressant metabolized primarily by the liver and
      small intestine. The pharmacokinetics (PK) of CyA-were studied in 6 patients
      prior to and 1 to 3 months after liver transplantation (tx). Sixteen blood
      samples were collected over 24 hours following a 2-3 mg/kg intravenous dose of
      CyA. PK parameters, presented as mean +/- SD, were estimated using
      noncompartmental techniques. Pre-tx AUCs (14,540 +/- 5200 micrograms.h/L) were
      found to be significantly higher than during the post-tx phase (8120 +/- 2870
      micrograms.h/L, p = 0.04). CyA clearance values were lower pre-tx as compared to
      post-tx (0.21 +/- 0.06 L/h/kg vs. 0.38 +/- 0.14 L/h/kg, respectively). There was
      no change in volume of distribution. End-stage liver disease can markedly
      decrease hepatic clearance of CyA relative to patients with stable hepatic
      function post-liver tx. The degree of impairment in clearance is not consistent
      or predictable based on liver function tests.

PMID- 12520627
TI  - Pharmacokinetics and renal effects of cidofovir with a reduced dose of probenecid
      in HIV-infected patients with cytomegalovirus retinitis.
AB  - To reduce possible nephrotoxicity, intravenous prehydration with normal saline
      and administration of probenecid must be used with each infusing of the antiviral
      cidofovir. The recommended standard-dose probenecid (SDP) regimen is 2 g at 3
      hours before cidofovir, then 1 g at 2 and 8 hours after cidofovir (total 4 g). A
      new regimen of reduced-dose probenecid (RDP), 2 g at 1 hour before cidofovir
      without additional probenecid administrations after infusion (total 2 g), was
      compared with SDP using a randomized, open-label, parallel design. A single dose
      of cidofovir (5 mg/kg) was given as a 1-hour infusion after saline prehydration
      to 24 HIV-infected patients (11 males, 13 females) with cytomegalovirus retinitis
      and good renal function. Blood was sampled for 48 hours and urine for 24 hours
      after the start of the cidofovir infusion. Cidofovir pharmacokinetics did not
      differ significantly between groups. Average key pharmacokinetic parameters
      (Cmax, tmax, lambda z, AUC0-infinity, Vss, CL, CLR, fe, ER) for RDP differed by
      less than 17% from SDP and were consistent with previously reported SDP data.
      Renal function parameters, other safety endpoints, and adverse events were
      similar between the groups. Therefore, the reduced-dose regimen of probenecid
      provided renal protection after a single dose of cidofovir and did not alter the
      pharmacokinetics of cidofovir in patients with moderately good renal function.
      Although the overall pharmacokinetic results do not show a significant difference
      in cidofovir exposure with the new probenecid regimen, the main issue of safety
      of the new dose regimen, both relating to renal toxicity and probenecid-related
      adverse events, is not adequately addressed in a small study.

PMID- 12520629
TI  - The influence of gender and food on the pharmacokinetics of sodium oxybate oral
      solution in healthy subjects.
AB  - Sodium oxybate (Xyrem; gamma-hydroxybutyrate) oral solution was recently approved
      in the United States for the treatment of cataplexy in patients with narcolepsy.
      Two single-center, randomized, open-label studies in healthy volunteers receiving
      single oral 4.5-g doses of sodium oxybate evaluated effects of (1) gender on
      oxybate pharmacokinetics and (2) food on its oral bioavailability. In the latter
      study, one dose was administered after an overnight fast, another after a high
      fat meal; 1 week separated treatments. Sodium oxybate pharmacokinetics was not
      significantly different between sexes. However, food significantly altered the
      bioavailability of oxybate by decreasing mean peak plasma concentration,
      increasing median time-to-peak concentration, and decreasing the area under the
      plasma concentration-time curve. Food did not affect elimination and urinary
      excretion of unchanged drug. No dose adjustment of sodium oxybate based on sex is
      indicated. Although significant food effects were observed, these are minimized
      in patients by the nocturnal dosing of sodium oxybate hours after the evening
      meal at a consistent time interval following food ingestion.

PMID- 12520628
TI  - The effect of food on the bioavailability of norethindrone and ethinyl estradiol
      from norethindrone acetate/ethinyl estradiol tablets intended for continuous
      hormone replacement therapy.
AB  - As part of the development of a combination product containing norethindrone
      acetate and low-dose ethinyl estradiol for continuous hormone replacement therapy
      in postmenopausal women, a study was conducted to determine the effect of a high
      fat meal on the bioavailability of norethindrone and ethinyl estradiol from
      tablets containing 1 mg norethindrone acetate/10 micrograms ethinyl estradiol.
      Eighteen healthy postmenopausal women participated in an open-label, single-dose,
      randomized, three-way crossover study in which 2 x 1/10 norethindrone
      acetate/ethinyl estradiol tablets were administered fasting and with a high-fat
      breakfast, and the same dose was administered in solution. Following each
      treatment, serial blood samples were collected for 48 hours, and plasma ethinyl
      estradiol and norethindrone concentrations were determined by a validated gas
      chromatography/mass spectrometry (GC/MS) method. Individual plasma ethinyl
      estradiol and norethindrone pharmacokinetic parameters were calculated by
      noncompartmental methods for each treatment and analyzed by ANOVA to obtain
      differences between least squares treatment mean values and associated 90%
      confidence intervals. Rates of ethinyl estradiol and norethindrone availability
      from tablets administered with food were slower than availability rates from
      tablets administered while fasting. Systemic exposure to ethinyl estradiol was
      unaffected by administration of tablets with food, whereas exposure to
      norethindrone increased by 27%. Because administration of norethindrone
      acetate/ethinyl estradiol 1/10 tablets with a high-fat meal did not decrease
      systemic exposure to norethindrone and ethinyl estradiol, this formulation can be
      taken without regard to meals.

PMID- 12520630
TI  - Safety and pharmacokinetics of ReN1869: a first human dose study in healthy
      subjects after single-dose administration.
AB  - ReN1869 (NNC 05-1869) is a novel, selective H1 receptor antagonist that has been
      developed for analgesic purposes. In a first human dose administration study, the
      safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95
      mg ReN1869 were studied. The study was a randomized, double-blind, placebo
      controlled, dose-escalating study in 56 healthy subjects. No serious or severe
      adverse events were reported. After active doses, an average of 0.6 adverse
      events (AEs) was reported per subject in comparison to 0.5 AEs per subject after
      placebo, and the frequency of subjects reporting AEs was not related to dose
      level. The most frequently reported adverse events were dizziness, fatigue, and
      somnolence, and their occurrence was not proportional to dose. Vital signs, ECG
      recordings, and clinical laboratory results showed no changes of clinical
      relevance. During telemetric monitoring at all dose levels until 4 hours after
      dosing, no clinically relevant abnormalities were observed. A maximally tolerated
      dose was not identified. ReN1869 was rapidly absorbed after dosing. The overall
      mean value of t1/2 and oral clearance was 4.7 hours and 11.7 L/h, respectively.
      The parameters Cmax and AUC increased proportionally with dose level, whereas all
      other pharmacokinetic parameters were independent of the dose. In conclusion,
      single-dose administration of ReN1869 in doses up to 95 mg exhibited very few
      adverse events and no clinically relevant effects on any of the observed safety
      parameters. The pharmacokinetics points to simple first-order pharmacokinetics
      for ReN1869. All together, it makes ReN1869 a potential new drug candidate for
      the treatment of chronic pain and inflammatory conditions of neurogenic origin.

PMID- 12520631
TI  - Pharmacokinetics and pharmacodynamics of a novel nizatidine controlled-release
      formulation in healthy subjects.
AB  - The pharmacokinetics and intragastric pH effects of a novel nizatidine controlled
      release (CR) formulation were compared to a currently marketed immediate-release
      (IR) nizatidine formulation (Axid). The bimodal pulsatile release characteristics
      of nizatidine CR decreased its Cmax by approximately 42% compared to nizatidine
      IR while maintaining 90% relative bioavailability; tmax was approximately 1.6
      times longer with the CR formulation. These characteristics enabled controlled
      release nizatidine to sustain effective plasma drug concentrations for a greater
      duration than immediate-release nizatidine over the dosing intervals. In multiple
      doses, the 24-hour AUC ratio for all comparisons of nizatidine CR 150 mg bid,
      nizatidine CR 300 mg daily, and nizatidine IR 150 mg bid was between 97% and 99%.
      Mean pH AUC values for nizatidine CR 150 mg bid and nizatidine IR 150 mg bid were
      similar overall during the 0- to 14-hour and 14- to 24-hour dosing intervals. For
      the 14- to 24-hour dosing interval, nizatidine CR 150 mg maintained gastric pH
      over 3.0 and 4.0 for 42% and 27% of the time compared to 39% and 23% for
      nizatidine IR, respectively. Nizatidine CR 300 mg, compared to the 150-mg CR and
      IR regimens, had a greater effect on increasing evening intragastric pH, thus
      providing support for the potential utility of nizatidine CR 300 mg dosed at
      night in alleviating nocturnal symptoms of gastroesophageal reflux disease.

PMID- 12520632
TI  - Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans.
AB  - The metabolic activity of CYP2C9 in 16 subjects expressing four different
      genotypes (CYP2C9*1/*1, *1/*2, *1/*3, and *2/*2) was evaluated. Single oral doses
      of tolbutamide, flurbiprofen, and losartan were administered in a randomized,
      crossover design. Plasma and urine were collected over 24 hours. The urinary
      metabolic ratio and amount of metabolite(s) excreted were correlated with
      formation clearance. The formation clearance of tolbutamide to its CYP2C9
      mediated metabolites demonstrated a stronger association with genotype compared
      to flurbiprofen and losartan, respectively (r2 = 0.64 vs. 0.53 vs. 0.42). A
      statistically significant correlation was observed between formation clearance of
      tolbutamide and the 0- to 12-hour urinary amount of 4'-hydroxytolbutamide and
      carboxytolbutamide (r = 0.84). Compared to tolbutamide, the correlations observed
      between the respective measures of flurbiprofen and losartan metabolism were not
      as strong. Tolbutamide is a better CYP2C9 probe than flurbiprofen and losartan,
      and the 0- to 12-hour amount of 4'-hydroxytolbutamide and carboxytolbutamide is
      the best urinary measure of its metabolism.

PMID- 12520633
TI  - Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified
      orange juice in healthy volunteers.
AB  - Previous work has demonstrated that the chelation interaction seen with
      ciprofloxacin when it is coadministered with antacids also happens when it is
      coadministered with calcium-fortified foods. This study was conducted to study
      whether this was a drug-specific finding or whether the interaction occurs with
      other members of the fluoroquinolone class of drugs. Sixteen healthy volunteers
      received single 400-mg oral doses of gatifloxacin with 12 ounces each of water,
      nonfortified orange juice, and calcium-fortified orange juice and had plasma
      samples drawn for assay over the subsequent 48 hours. Results demonstrated
      significant increases in total oral clearance (15%) and volume of distribution
      (13%) along with a matching significant decrease (12%) in exposure (AUC) when
      gatifloxacin was taken with the fortified juice. Although not statistically
      significant, peak concentrations decreased by 15% and were reached (tmax)
      approximately 38% later when gatifloxacin was coadministered with the calcium
      fortified juice. Bioavailability testing indicated that although the 90%
      confidence intervals (CIs) for the ratio of the geometric means of the calcium
      fortified juice and water arms' AUC stayed within the range of 80% to 125%, those
      for Cmax did not. This study demonstrated a chelation or adsorption interaction
      between the fortified juice and gatifloxacin that reached regulatory
      significance. As a result, clinicians may wish to instruct patients to take
      gatifloxacin either with nonfortified foods or on an empty stomach.

PMID- 12520634
TI  - Capecitabine/irinotecan in colorectal cancer: European early-phase data and
      planned trials.
AB  - Capecitabine (Xeloda) and irinotecan (CPT-11, Camptosar) exhibit single-agent
      activity in colorectal cancer, have nonoverlapping major toxicities, and exhibit
      a synergistic effect in tumor xenograft models. European early-phase trials of
      the combination in patients with metastatic colorectal cancer indicate good
      response rates across doses tested and manageable toxicities, with available data
      supporting use of a regimen of oral capecitabine at 1,000 mg/m2 twice daily on
      days 1 to 14 plus IV irinotecan at 250 mg/m2 on day 1 every 21 days in this
      setting. The European Organisation for Research and Treatment of Cancer has
      planned a phase III trial (EORTC 40015) comparing this regimen of
      capecitabine/irinotecan with infusional fluorouracil (5-FU)/leucovorin plus
      irinotecan in approximately 700 patients with metastatic colorectal cancer. The
      QUASAR (Quick and Simple and Reliable) 2 adjuvant trial will compare 5
      FU/leucovorin with capecitabine/irinotecan given over 6 months as adjuvant
      therapy in patients with stage II/III colorectal cancer. These trials will help
      define the roles of this combination in the treatment of colorectal cancer.

PMID- 12520635
TI  - Current status of capecitabine in the treatment of colorectal cancer.
AB  - Capecitabine (Xeloda) is an oral prodrug that is enzymatically converted to
      fluorouracil (5-FU) within cancer cells. Data from two large phase III trials
      performed in patients receiving first-line chemotherapy for metastatic colorectal
      cancer showed that capecitabine yielded higher objective response rates and
      equivalent median time to tumor progression and overall survival rates as 5
      FU/leucovorin. In these studies, capecitabine demonstrated lower rates of
      diarrhea, stomatitis, nausea, and severe neutropenia than bolus 5-FU/leucovorin,
      but a higher rate of hand-foot syndrome and hyperbilirubinemia. The natural
      extension of this work has been to evaluate substitution of capecitabine for 5
      FU/leucovorin in combination chemotherapy trials with irinotecan (CPT-11,
      Camptosar) or oxaliplatin (Eloxatin). This is especially important due to
      concerns regarding toxicities observed with regimens that combine bolus 5
      FU/leucovorin with irinotecan or oxaliplatin. Phase I/II and phase II trials of
      capecitabine in combination with irinotecan or oxaliplatin in patients with
      advanced disease indicate that the combinations are well tolerated and produce
      response rates that are in the range of those that would be expected with
      infusional 5-FU/leucovorin combined with irinotecan or oxaliplatin. Phase III
      trials have been initiated in the advanced disease and adjuvant settings and
      should help determine the efficacy, toxicity, and tolerability of the
      capecitabine/irinotecan or capecitabine/oxaliplatin combination in direct
      comparison to intravenous 5-FU/leucovorin and irinotecan or oxaliplatin.

PMID- 12520636
TI  - Can capecitabine replace 5-FU/leucovorin in combination with oxaliplatin for the
      treatment of advanced colorectal cancer?
AB  - The combination of capecitabine (Xeloda) and oxaliplatin (Eloxatin), or XELOX, is
      an effective and safe approach to the treatment of advanced colorectal cancer,
      with the potential advantage of convenience over standard combination regimens.
      In a large multicenter phase II trial for patients with metastatic colorectal
      cancer (N = 96), first-line treatment with oral capecitabine at 1,000 mg/m2 twice
      daily for 14 days and oxaliplatin at 130 mg/m2 by 2-hour infusion on day 1 every
      21 days produced objective response in 55% of patients and stable disease
      (greater than 3 months) in a further 32%. Preliminary data indicate a median
      progression-free survival of 7.6 months (with 14% of patients still having not
      progressed) and median survival of over 16 months (with 59% of patients still
      alive); the 1-year survival rate was 72%. Grade 3 or 4 toxicity was relatively
      infrequent; in particular, grade 3 hand-foot syndrome occurred in just 3% of
      patients and severe neutropenia in only 6%. Treatment delivery was highly
      successful, with a median of 10 cycles being administered (range: 1-23 cycles).
      Both efficacy and safety outcomes with the XELOX combination compare well with
      those observed with infusional fluorouracil (5-FU)/leucovorin plus oxaliplatin
      (FOLFOX4) in first-line treatment for advanced disease. However, 3-weekly XELOX
      requires less time in hospital and is simpler than the 2-weekly standard FOLFOX4
      regimen. Phase III trials comparing XELOX with infusional 5
      FU/leucovorin/oxaliplatin are ongoing.

PMID- 12520637
TI  - Capecitabine and radiation therapy for advanced gastrointestinal malignancies.
AB  - Accumulating data indicate a beneficial effect of combining infusional
      fluorouracil (5-FU) with radiation therapy in gastrointestinal cancers, and phase
      II/III studies are under way to examine this approach in a variety of tumor
      types. The oral fluoropyrimidine capecitabine (Xeloda) provides a more convenient
      approach to radiosensitization. The agent has good single-agent activity in a
      variety of tumor types. The final step in activation of the drug to 5-FU occurs
      via activity of thymidine phosphorylase; thymidine phosphorylase activity is
      markedly upregulated in many tumor tissues compared with healthy tissue (Miwa M,
      Ura M, Nishida M, et al: Eur J Cancer 34:1274-1281, 1998), allowing greater
      accumulation of 5-FU in tumor tissue, and there is evidence indicating that
      radiation therapy results in augmented upregulation of this enzyme. A variety of
      data suggest benefits of 5-FU as a radiosensitizer in improving outcome of
      radiation therapy in a number of gastrointestinal cancers, including data
      indicating improved survival with this chemoradiation therapy approach.
      Prospective and randomized studies of 5-FU-based chemoradiation are under way in
      esophageal, gastric, biliary tract, pancreatic, rectal, and anal cancer. Early
      phase studies are planned to examine the combination of capecitabine, celecoxib
      (Celebrex), and radiation therapy in esophageal cancer and pancreatic cancer and
      to compare the effects of capecitabine and capecitabine/oxaliplatin (Eloxatin)
      with radiation therapy in rectal cancer. A phase III trial comparing capecitabine
      and infusional 5-FU in chemoradiation therapy in rectal cancer has also been
      planned. Additional studies should be conducted in gastric, biliary tract, and
      anal cancer. Capecitabine shows promise in replacing infusional 5-FU as the
      platform for gastrointestinal chemoradiation therapy.

PMID- 12520639
TI  - Pancreatic cancer: epidemiology, genetics, and approaches to screening.
AB  - Pancreatic cancer is a leading cause of cancer-related mortality. Treatment has
      limited efficacy, and 5-year survival rates remain less than 5%. Insights from
      epidemiology and discoveries in molecular genetics have laid the groundwork for a
      rational screening strategy for high-risk individuals. High-risk populations
      include those in their 6th to 8th decades of life, those with a family history of
      pancreatic cancer, and those with a personal history of tobacco smoking. Roughly
      10% of cases are due to an inherited genetic susceptibility. Several familial
      syndromes with known genetic defects have been implicated, but the majority of
      familial cases result from as yet undefined genes. Acquired mutations have been
      identified in the oncogenes K-ras and HER2/neu, and in the tumor suppressor genes
      p16, p53, SMAD4, and BRCA2. No standard for screening or prevention exists, but
      strategies employing endoscopic, radiologic, and molecular methods to screen high
      risk individuals are under investigation.

PMID- 12520638
TI  - Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor
      activity.
AB  - We hypothesized that hand-foot syndrome is an inflammatory phenomenon mediated by
      the overexpression of cyclooxygenase 2 (COX-2). Therefore, a specific COX-2
      inhibitor such as celecoxib (Celebrex) could attenuate both the incidence and
      severity of hand-foot syndrome. We undertook a retrospective study comparing the
      incidences of hand-foot syndrome in 67 patients with metastatic colorectal cancer
      who took capecitabine (Xeloda) with or without celecoxib. Surprisingly, celecoxib
      seemed to attenuate capecitabine-induced diarrhea as well. Capecitabine/celecoxib
      was also associated with increased tumor response, proportion of stable disease
      (62.5% vs 22.8%, P = .001), and increase in median time to tumor progression (6
      vs 3 months, P = .002) compared with capecitabine alone, despite the fact that
      patients on capecitabine/celecoxib had less favorable disease characteristics
      (age, performance status, and prior chemotherapies). Overexpression of COX-2,
      implicated in promoting angiogenesis, enhanced tumor invasiveness, evasion of
      apoptosis, and immune suppression, is a bona fide molecular target for many solid
      tumors, including colorectal cancer. Combining capecitabine with celecoxib in the
      treatment of colorectal cancer has strong preclinical rationales. A prospective
      study is being designed to evaluate capecitabine and celecoxib with or without
      epidermal growth factor receptor antagonist ZD1839 in the frontline treatment of
      metastatic colorectal cancer. These regimens under study are orally based and may
      significantly impact quality of life in the frontline treatment of metastatic
      colorectal cancer.

PMID- 12520640
TI  - Is there a role for dose-intensive chemotherapy with stem cell rescue in breast
      cancer?
AB  - Over the past decade, high-dose chemotherapy with autologous bone marrow and/or
      peripheral blood rescue has been increasingly used to treat women with breast
      cancer. Laboratory and clinical studies have shown that dose intensity may be
      important in treating selected patients with breast cancer. Initial phase I
      studies showed good response rates of short durations. Further trials in
      metastatic disease with high-dose chemotherapy and stem cell rescue earlier in
      the treatment course had been encouraging. However, the optimal timing of high
      dose chemotherapy remains a question. In addition, randomized trials in high-risk
      early-stage breast cancer have completed accrual. Technologic improvements in
      stem cell procurement and hematopoietic growth factors have contributed to
      decreased morbidity and mortality. This review will discuss the role of such
      therapy in the treatment of women with breast cancer.

PMID- 12520641
TI  - Clinical trials referral resource. Clinical trials in ovarian cancer, Part 2.

PMID- 12520642
TI  - Advances in the treatment of gynecologic malignancies. Part 2: Cancers of the
      uterine corpus and ovary.
AB  - Over the past few decades, we have gained a better understanding of the risk
      factors associated with the recurrence of endometrial cancer. Adjuvant
      postoperative radiotherapy in an intermediate-risk group of endometrial cancer
      patients resulted in improvement in local control, but survival was not improved
      significantly. Postoperative management of uterine sarcomas remains
      investigational. The management of ovarian cancer has notably advanced during the
      1990s. Platinum- and paclitaxel-based combination chemotherapy set a new standard
      of care for patients with advanced ovarian cancer. During the late 1990s, a trend
      emerged favoring the use of carboplatin over cisplatin for first-line management
      of advanced ovarian cancer because of its more favorable safety profile. Adjuvant
      therapy for early-stage high-risk ovarian cancer continues to be actively
      investigated.

PMID- 12520643
TI  - Plastic surgery: a component in the comprehensive care of cancer patients.
AB  - Plastic surgery represents a small but critical component of the comprehensive
      care of cancer patients. Its primary role in the treatment of cancer patients is
      to extend the ability of other surgeons and specialists to more radically treat
      cancer, offering patients the best opportunity for cure. Although the most
      convincing data for improved psychosocial well-being through plastic surgery is
      in the setting of breast cancer reconstruction after mastectomy, it is reasonable
      to assume that all patients who undergo major reconstruction to minimize
      deformity due to cancer therapy feel some improvement in quality of life. This
      article will provide an overview of the role of plastic surgery in cancer
      treatment.

PMID- 12520644
TI  - Cytokines in septic shock.

PMID- 12520645
TI  - Chlamydia pneumoniae and the heart: impact of diagnostic methods.

PMID- 12520646
TI  - Impetigo: etiology and therapy.

PMID- 12520647
TI  - West Nile virus in the US and abroad.

PMID- 12520649
TI  - Life threatening infections in the asplenic or hyposplenic individual.

PMID- 12520648
TI  - Blastomycosis: Gilchrist's disease revisited.

PMID- 12520650
TI  - Update on Q fever, including Q fever endocarditis.

PMID- 12520651
TI  - The direct and indirect effects of infection in liver transplantation:
      pathogenesis, impact, and clinical management.

PMID- 12520652
TI  - The potential roles of C-reactive protein and procalcitonin concentrations in the
      serum and cerebrospinal fluid in the diagnosis of bacterial meningitis.

PMID- 12520653
TI  - Testing for genital herpes: how, who, and why.

PMID- 12520654
TI  - A review of progressive multifocal leukoencephalopathy in persons with and
      without AIDS.

PMID- 12520655
TI  - Diagnosis and management of empyema.

PMID- 12520656
TI  - Use of antiretroviral drugs to prevent sexual transmission of HIV.

PMID- 12520657
TI  - Pneumococcal vaccines for infants and children--past, present, and future.

PMID- 12520658
TI  - [Quo vadis radioimmuno- and radiopeptide therapy? What roles do they play in the
      everyday clinical setting?].

PMID- 12520659
TI  - PET in patients with clear-cut multiple chemical sensitivity (MCS).
AB  - AIM: Multiple chemical sensitivity (MCS) is a controversially discussed symptom
      complex. Patients afflicted by MCS react to very low and generally non-toxic
      concentrations of environmental chemicals. It has been suggested that MCS leads
      to neurotoxic damage or neuroimmunological alteration in the brain detectable by
      position emission tomography (PET) and single photon emission computer tomography
      (SPECT). These methods are often applied to MCS patients for diagnosis, although
      they never proved appropriate. METHOD: We scanned 12 MCS patients with PET,
      hypothesizing that it would reveal abnormal findings. RESULTS: Mild glucose
      hypometabolism was present in one patient. In comparison with normal controls,
      the patient group showed no significant functional brain changes. CONCLUSION:
      This first systematic PET study in MCS patients revealed no hint of neurotoxic or
      neuroimmunological brain changes of functional significance.

PMID- 12520660
TI  - Does an individual estimation of halflife improve the results of radioiodine
      therapy of Graves' disease?
AB  - AIM: The impact of our dosimetry concept on radioiodine therapy success in
      Graves' disease (GD) was analysed. Three questions arised: Did individual
      estimation of pretherapeutic halflife improve therapeutic success? Did individual
      dosimetry result in accurate dose calculation? Did antithyroid medication have a
      measurable influence on therapeutic success under the prevailing conditions?
      METHODS: 126 consecutive patients were treated with 200 Gy I-131 in our therapy
      ward for GD and followed-up six to nine months after therapy. Success quote was
      assessed using a standardized protocol and treatment was classified as successful
      when the patient was eu- or hypothyroid, or unsuccessful when he or she presented
      with a suppressed TSH-level or in hyperthyroid condition after antithyroid
      medication withdrawal. Antithyroid medication, activity I-131, dose,
      concentration of fT3 and fT4, specific delivered dose and halflife were put into
      a multiple regression model to assess their influence on therapeutic success. In
      order to assess possible factors disturbing the therapeutic outcome, relevant
      parameters were analyzed using Logit transformation. RESULTS: Out of 126 patients
      84 were classified as successfully treated and 42 (33.3%) as failures. A
      significant influence on the outcome only was found for thyroid mass. However,
      therapeutic success appeared to be more distinctly determined by the specific
      delivered dose using an estimated halflife of 5.5 days (Odds: 10.0, p < 0.001).
      Accurate intratherapeutic dosimetry did not play a significant role to enhance
      therapeutic success. Neither did antithyroid medication during radioiodine
      therapy exert any significant impact. CONCLUSIONS: Measurement of individual
      intratherapeutic halflife as opposed to an estimate using a standard halflife did
      not provide improved results concerning the target dose. Retrospectively, the
      therapeutic outcome on the basis of a measured halflife as compared to a standard
      halflife did not significantly improve. In addition, no influence of antithyroid
      medication on therapy success was found.

PMID- 12520661
TI  - Radioiodine treatment of feline hyperthyroidism in Germany.
AB  - AIM: Establishment of radioiodine treatment of feline hyperthyroidism in
      veterinary routine in accordance with German radiation protection regulations.
      PATIENTS AND METHODS: 35 cats with proven hyperthyroidism were treated with 131I
      in a special ward. Thyroid uptake and effective halflife were determined using
      gammacamera dosimetry. Patients were released when measured whole body activity
      was below the limit defined in the German "Strahlenschutzverordnung". RESULTS:
      17/20 cats treated with 150 MBq radioiodine and 15/15 cats treated with 250 MBq
      had normal thyroid function after therapy, normal values for FT3 and FT4 were
      reached after two and normal TSH levels after three weeks. In 14 cats normal
      thyroid function was confirmed by controls 3-6 months later. Thyroidal iodine
      uptake was 24 +/- 10%, effective halflife 2.5 +/- 0.7 days. Whole body activity <
      1 MBq was reached 13 +/- 4 days after application of 131I. Radiation exposure of
      cat owners was estimated as 1.97 microSv/MBq for adults. CONCLUSION: Radioiodine
      therapy of feline hyperthyroidism is highly effective and safe. It can easily be
      performed in accordance with German radiation protection regulations, although
      this requires hospitalisation for approximately two weeks. Practical
      considerations on radiation exposure of cat owners do not justify this long
      interval. Regulations for the veterinary use of radioactive substances similar to
      existing regulations for medical use in humans are highly desirable.

PMID- 12520662
TI  - [Cervical tuberculosis in a thyroid gland cyst].

PMID- 12520663
TI  - Unusual radioiodine uptake in a patient with thyroid cancer and cranial metallic
      clips.

PMID- 12520664
TI  - User based pacemaker and ICD registries.

PMID- 12520665
TI  - High quality performance of pacemakers and implantable defibrillators.

PMID- 12520666
TI  - Changing trends in pacemaker and implantable cardioverter defibrillator generator
      advisories.
AB  - Pacemaker and implantable cardioverter defibrillator (ICD) generator recalls and
      safety alerts (advisories) occur frequently, affect many patients, and are
      increasing in number and rate. It is unknown if advances in device technology
      have been accompanied by changing patterns of device advisory type. Weekly FDA
      Enforcement Reports from January 1991 to December 2000 were analyzed to identify
      all advisories involving pacemaker and ICD generators. This article represents
      additional analysis of previously cited advisories and does not contain
      additional recalls or safety alerts over those that have been previously
      reported. The 29 advisories (affecting 159,061 devices) from the early 1990s
      (1991-1995) were compared to the 23 advisories (affecting 364,084 devices) from
      the late 1990s (1996-2000). While the annual number of device advisories did not
      change significantly, ICD advisories became more frequent and a three-fold
      increase in the number of devices affected per advisory was observed. The number
      of devices affected by hardware advisories increased three-fold, due primarily to
      a 700-fold increase in electrical/circuitry abnormalities and a 20-fold increase
      in potential battery/capacitor malfunctions. Other types of hardware
      abnormalities (defects in the device header, hermetic seal, etc.) became less
      common. The number of devices recalled due to firmware (computer programming)
      abnormalities more than doubled. The remarkable technological advances in
      pacemaker and ICD therapy have been accompanied by changing patterns of device
      advisory type. Accurate, timely physician and patient notification systems, and
      routine pacemaker and ICD patient follow-up continue to be of paramount
      importance.

PMID- 12520667
TI  - Rate responsive pacing using transthoracic impedance minute ventilation sensors:
      a multicenter study on calibration stability.
AB  - Previous studies showed that transthoracic impedance minute ventilation (IMV), as
      measured by a pacemaker sensor, is closely correlated to actual minute
      ventilation (VE) determined by standard methods. The aim of this study was to
      analyze the changes in the calibration between IMV and VE at rest and during
      exercise over time. Fifteen patients (age 60 +/- 13 years) with Medtronic Kappa
      400 pacemakers completed a baseline visit followed by two visits separated by 1
      month and 1 week, respectively. In each patient, VE (L/min) was monitored at rest
      in the supine and sitting positions and during graded bicycle ergometer exercise
      using a standard cardiopulmonary metabolic gas analysis system with simultaneous
      recording of IMV (omega/min) using DR-180 extended telemetry monitors.
      Calibration at rest was defined as the ratio of IMV to VE, calculated from 1
      minute average values in the supine and sitting positions. Calibration during
      bicycle exercise was defined as intercept (IMV value at VE = 10 L/min-typical VE
      value at beginning of exercise), and slope of the IMV/VE regression line. The
      calibration of IMV showed individual variability over time. The magnitude
      (absolute value) of observed fractional changes in calibration at 1 month was
      0.23 +/- 0.20 (rest-supine), 0.20 +/- 0.15 (rest-sitting), 0.18 +/- 0.19
      (exercise-intercept), 0.28 +/- 0.35 (exercise-slope), and 0.18 +/- 0.15, 0.15 +/-
      0.09, 0.28 +/- 0.39, and 0.27 +/- 0.15, respectively, at 1 week. The magnitude of
      change at 1 month was not statistically different from the magnitude of change at
      1 week. In conclusion, the calibration of IMV, as measured by a pacemaker sensor,
      versus actual VE may demonstrate variability. However, this study also suggests
      that the observed changes are not cumulative over time. These results have
      implications for patient monitoring applications using these sensors and for
      development of future pacemaker rate response algorithms.

PMID- 12520668
TI  - Pacemaker therapy in isolated congenital complete atrioventricular block.
AB  - The aim of this study was to evaluate the effect of pacemaker (PM) therapy in
      patients with isolated congenital complete atrioventricular block (CCAVB).
      Patients with CCAVB eventually quality for PM implantation, however, timing
      remains controversial. Retrospective evaluation of left ventricular end-diastolic
      diameter (LVEDD), shortening fraction (SF), and cardiothoracic ratio (CTR) in 149
      CCAVB patients, before, at, and after PM implantation was carried out. LVEDD
      shows an average increase of 0.48%/month in non-PM patients, and an average
      decrease of 0.88%/month in PM patients. SF shows an average increase of
      0.10%/month in non-PM, and an average decrease of 0.32%/month in PM patients. CTR
      shows an average increase of 0.02%/month in non-PM, and an average decrease of
      0.19%/month in PM patients. The difference between the non-PM and PM groups is
      significant (P = 0.05) for all variables. Symptomatic patients show no
      significant change in LVEDD after PM therapy (from 66.5% before to 68.5% after PM
      therapy). Asymptomatic patients do show a significant (P < 0.001) decrease in
      LVEDD after PM therapy (from 78.4% before to 73.3% after PM therapy). CTR does
      not differ significantly between symptomatic and asymptomatic patients before PM
      therapy (58% and 57%, respectively). CTR does differ significantly (P < 0.001)
      between symptomatic and asymptomatic patients after PM therapy (52% and 48%,
      respectively). Heart size and SF are increased in most patients with isolated
      CCAVB. PM implantation is associated with a decrease in heart size and
      normalization of SF in most patients. Indications for PM therapy in children may
      require reevaluation in asymptomatic patients with increased cardiac size and
      decreased cardiac function.

PMID- 12520669
TI  - Single lead DDD pacing using electrodes with longitudinal and diagonal atrial
      floating dipoles.
AB  - In this study, an assessment was made of the possibilities of single lead DDD
      pacing in two groups: a group of 15 patients in whom a lead with a longitudinal
      atrial "floating" dipole was implanted, and another group of 10 patients with a
      lead with a diagonal atrial "floating" dipole. In both groups, the electrodes
      were connected to a SLD generator. At discharge, atrial capture was achieved with
      the unipolar mode in 17 of 25 patients, whereas in the group carrying the
      longitudinal atrial dipole, atrial capture was achieved with the overlapping
      biphasic impulses (OLBI) system in 12 of 15 patients and in all 10 patients in
      the group with the diagonal atrial dipole. At 3 months, atrial capture was
      achieved with the unipolar mode in 13 of 22 patients (5.75 +/- 1.77 V/0.5 ms),
      whereas with the OLBI system atrial capture was achieved in 8 of 13 patients
      carrying the longitudinal atrial dipole (3.11 +/- 1.13 V/0.5 ms), and in 8 of the
      9 patients carrying the diagonal atrial dipole (2.80 +/- 0.69 V/0.5 ms). In this
      study, the use of the OLBI system led to a significant reduction of atrial
      threshold (P < 0.0001). Phrenic stimulation is the main untoward effect reported
      during single lead DDD pacing, a lower incidence being detected in the group
      carrying the diagonal atrial dipole (10 vs 35.7%, P = NS). Other limitations of
      this form of pacing could result from a crossed stimulation phenomenon detected
      in a patient during single lead DDD pacing.

PMID- 12520670
TI  - Radiofrequency ablation of cardiac arrhythmias using a three-dimensional real
      time position management and mapping system.
AB  - A recently developed three-dimensional real-time position management system (RPM)
      uses an ultrasound ranging technique that enables multiple distance measurements
      between two reference catheters and a mapping catheter each equipped with
      ultrasound transducers. In addition to three-dimensional representation of the
      catheters and ablation sites it displays real-time movements of catheters
      (including the tip and shaft). A recently released version of the system enables
      additional geometry reconstruction of the heart chamber and activation mapping.
      This study included 21 patients (mean age 59 +/- 14.5 years) referred for
      radiofrequency catheter ablation of various arrhythmias. Geometry was
      reconstructed by tracing the endocardial contour of the respective heart
      chambers. Global and local color coded activation maps were constructed to
      confirm the nature of arrhythmia and to guide ablation. Spontaneous or induced
      arrhythmias were typical atrial flutter (n = 8), atypical atrial flutter (n = 3),
      atrioventricular nodal reentrant tachycardia (n = 3), atrial tachycardia (n = 2),
      atrial fibrillation (n = 2), ventricular tachycardia (n = 2), and Wolff-Parkinson
      White syndrome (n = 1). Geometry reconstruction and mapping of arrhythmias were
      possible in 20 of 21 patients. RPM-guided radiofrequency ablation was successful
      in 19 (95%) of 20 patients. Due to difficulties in steering the RPM
      mapping/ablation catheter, in 6 (28%) successfully mapped patients,
      radiofrequency ablation was performed using another catheter. In one patient, the
      RPM-guided map was inconclusive and in another patient, ablation failed due to
      multiple reentrant circuits. No complications were observed. In conclusion, the
      new RPM system enables geometry reconstruction and three-dimensional positioning
      of the ablation catheters, reconstruction of the activation maps, marking of
      anatomic structures and reproducible tracking of multiple ablation sites. The
      system could be used to guide radiofrequency ablation of atrial and ventricular
      arrhythmias.

PMID- 12520671
TI  - Ventricular rate stabilization for the prevention of pause dependent ventricular
      tachyarrhythmias: results from a prospective study in 309 ICD recipients.
AB  - Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long
      short intervals preceding the onset of recurrent ventricular tachyarrhythmias.
      Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore,
      been suggested to prevent onset of pause dependent tachyarrhythmias. However, the
      clinical efficacy of this approach has not been studied systematically. In a
      prospective multicenter crossover study, patients were randomized to activation
      or deactivation of an implemented ventricular rate stabilization algorithm (VRS)
      after first implant of a dual chamber ICD. After 3 months, all patients were
      crossed over to the alternate programming. The rate of appropriate spontaneous VA
      episodes was compared between VRS On and VRS Off. Stored electrograms were
      reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall
      efficacy analysis was based on 309 patients enrolled in the study. Forty percent
      (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to
      treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized
      to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment
      basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P =
      0.24) was seen. In an extended Cox model adjusting for confounding variables, the
      relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95%
      CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in
      only 36 (8%) of 427 visually analyzed episodes. There was no significant
      reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On
      compared to the Off programming in this prospective study.

PMID- 12520672
TI  - Upgrade of permanent pacemakers and single chamber implantable cardioverter
      defibrillators to pectoral dual chamber implantable cardioverter defibrillators:
      indications, surgical approach, and long-term clinical results.
AB  - The aim of this study was to describe the indications for upgrade of pacemakers
      (PMs) or single chamber (VVIR) ICDs to dual chamber (DDDR) ICDs, surgical
      approach, hardware hybridization, and clinical outcome. Patients with preexisting
      PMs or VVIR ICDs may develop indications for ICD therapy or dual chamber pacing,
      respectively, that can be served by DDDR ICDs that incorporate preexisting
      transvenous leads. Fifty-seven patients underwent upgrade from PMs (29/57) or
      VVIR ICDs (28/57) to pectoral DDDR ICDs. Preexisting transvenous atrial and/or
      ventricular leads suitable for continued use were incorporated into new DDDR ICDs
      in 88.5% and 100% of PM and VVIR ICD upgrades, respectively. Acceptable DFTs were
      achieved in 56 (98.2%) of 57 patients. Appropriate VT/VF therapies were
      registered among 33.3% of patients during follow-up. No shocks due to lead noise
      were observed in any patient with hybridized transvenous leads. Atrial far-field
      R wave (FFRW) oversensing occurred in 24% of DDDR ICD systems incorporating a
      preexisting atrial lead. FFRW was overcome by programming reduced atrial
      sensitivity without interfering with the normal ICD system performance in all
      instances. Upgrade of PMs and VVIR ICDs to pectoral DDDR ICDs is safe and
      technically feasible in most patients. Preexisting transvenous leads can be
      successfully incorporated into new DDDR ICDs, simplifying the surgical procedure,
      minimizing transvenous hardware, and eliminating the possibility of hazardous
      pacemaker-ICD interactions.

PMID- 12520673
TI  - Continuous Holter telemetry of atrial electrograms and marker annotations using a
      common Holter recording system: impact on Holter electrocardiogram interpretation
      in patients with dual chamber pacemakers.
AB  - The impact of continuous telemetry of atrial electrogram and marker annotations
      on Holter ECG interpretation was assessed in 98 patients with bipolar dual
      chamber pacemakers (VDD pacemakers n = 29, DDD(R) systems n = 69). Atrial
      electrogram and marker annotations were continuously sampled by a telemetry coil
      that was externally positioned on the pacemaker pocket, amplified, and transduced
      to a three-channel Holter ECG recorder in addition to an ECG recording. Holter
      tapes were analyzed by two experienced investigators for quality of P wave
      recognition and episodes suspicious of pacemaker dysfunction. Initially, only the
      ECG channel was analyzed. Thereafter, results were compared to those achieved on
      the basis of the complete recording including atrial electrogram and marker
      annotations. Recognition of atrial rhythm was markedly improved by Holter
      telemetry. During 99.3% of recording time telemetry showed a satisfying quality,
      whereas ECG alone allowed a reliable P wave recognition only during 84.4% of
      recording time (P < 0.001). One hundred twenty-nine episodes suspicious of
      pacemaker malfunction occurred in 17 of 98 patients. By analysis of ECG, only
      78.3% of episodes were concordantly classified by the investigators. However,
      98.4% of all episodes were properly identified when atrial electrogram and marker
      annotations were added to the analysis (P < 0.001). In particular, discrimination
      between atrial undersensing, sinus bradycardia, and atrial sensed events within
      the refractory periods was facilitated. Holter telemetry of atrial electrogram
      and marker annotations facilitates the analysis of Holter ECGs in pacemaker
      recipients and improves the detection of pacemaker dysfunctions.

PMID- 12520674
TI  - Hemodynamic effect of the ventricular pacing site in fetal lambs with complete
      atrioventricular block.
AB  - Complete atrioventricular (AV) block in hydrops fetalis is associated with high
      mortality. Fetal ventricular pacing to restore ventricular rate can be an
      effective procedure, however, no fetal data has shown an appropriate epicardial
      ventricular pacing site. To evaluate the hemodynamic effect of right and left
      ventricular pacing in fetal lambs with complete AV block, a fetal complete AV
      block model was created. Aortic pressure, central venous pressure, and QRS
      duration were measured, and right and left ventricular output was estimated in
      seven fetal lambs. The uterus was opened under maternal anesthesia, and under
      local anesthesia, catheters were inserted into the fetal superior vena cava and
      ascending aorta through a neck incision. Pacing leads were then sutured onto the
      fetal right and left ventricular epicardium via a midline thoracotomy. Complete
      AV block was created by cryoablation of the AV node. Ventricular output was
      estimated using echocardiography by a transuterine approach. Fetal hemodynamics
      were observed before AV block creation (control), and after complete AV block
      creation with the right and left ventricular pacing set at 150/min. The right
      ventricular output was 320 +/- 66 mL/kg per minute at control, decreased to 243
      +/- 65 mL/kg per minute during right ventricular pacing (P < 0.05), and was 254
      +/- 61 mL/kg per minute during left ventricular pacing. The left ventricular
      output was 224 +/- 98 mL/kg per minute at control, 176 +/- 77 mL/kg minute during
      right ventricular pacing, and 178 +/- 67 mL/kg per minute during left ventricular
      pacing. Biventricular (combined ventricular) output was 544 +/- 134 mL/kg per
      minute at control, 419 +/- 114 mL/kg per minute during right ventricular pacing,
      and 432 +/- 100 mL/kg minute during left ventricular pacing. Systolic aortic
      pressure was 62.2 +/- 8.7 mmHg at control, 55.2 +/- 9.5 mmHg during right
      ventricular pacing, and 53.4 +/- 9.1 mmHg during left ventricular pacing. Central
      venous pressure (CVP) was 2.6 +/- 0.5 mmHg at control, 4.0 +/- 2.7 mmHg during
      right ventricular pacing, and 4.4 +/- 2.5 mmHg during left ventricular pacing.
      The QRS duration was 51 +/- 54 ms at control, but lengthened to 87 +/- 19 ms
      during right ventricular pacing and to 78 +/- 21 ms during left ventricular
      pacing (P < 0.05). In conclusion, the right ventricular output decreased during
      right ventricular pacing in fetal lambs with complete AV block, while it was
      preserved during the left ventricular pacing. Left ventricular pacing might be
      superior for treating hydropic fetuses with complete AV block.

PMID- 12520675
TI  - Isochronal difference mapping: an approach for mapping dynamic changes during
      reentrant ventricular tachycardia.
AB  - During clinical electrophysiological study for treatment of reentrant ventricular
      tachycardia, activation maps constructed from the acquired electrophysiological
      data can be difficult to interpret when the reentrant circuit is changing from
      one cardiac cycle to the next. Reduction of complexity would be beneficial but
      has been difficult. A new technical method termed isochronal difference mapping
      (IDM) was devised to reduce complexity and enhance distinctive conduction
      patterns present in the data. Electrograms were acquired from 196 sites using a
      canine model of a reentrant ventricular tachycardia circuit with a figure eight
      conduction pattern occurring in the epicardial border zone. Activation maps were
      constructed for all cardiac cycles during episodes of tachycardia in five
      experiments. IDM maps were then created, which are subtractive comparisons of the
      activation maps from two different cardiac cycles during a given tachycardia
      episode. In each map the electrical activation occurring for only one or for both
      of the cardiac cycles was separately highlighted in distinct spatial areas of the
      border zone during an isochronal interval. Based on the mappings, areas of
      conduction velocity change, regions of breakthrough of the wavefront across
      functional lines of block, regions with coherent activation, and regions with
      irregular activation became readily apparent. IDM maps showed that when cycle
      length prolonged due to deceleration of conduction within the reentrant circuit
      isthmus, conduction velocity increased elsewhere in the circuit. IDM accentuates
      cycle-to-cycle differences in multi-channel electrophysiological data and can be
      used to reduce complexity and enhance distinctive conduction patterns.

PMID- 12520676
TI  - Spectral analysis of chronic atrial fibrillation and its relation to minimal
      defibrillation energy.
AB  - The average rate of fibrillatory activity may reflect the global activation
      pattern of AF. Electrical cardioversion is the most effective method of
      converting chronic AF to sinus rhythm. The aim of this study was to investigate
      the relation between the minimal defibrillation energy requirement and the
      dominant frequency of chronic AF. Twenty-nine patients with chronic AF (mean
      duration 57.9 +/- 7.7 months) underwent external electrical cardioversion. Before
      cardioversion, the frequency content of the 60-second AF in ECG lead V1 was
      quantified using digital signal processing. After band-pass filtering, QRST
      complexes were cancelled using a recursive lease squares algorithm. The resulting
      fibrillatory baseline signal was subjected to fast Fourier transform and was
      displayed as a power spectrum. The dominant AF frequency was found to range from
      4.9 to 8.7 Hz (mean 6.7 +/- 0.9 Hz). Twenty-six patients had successful
      conversion of AF to sinus rhythm without immediate recurrence. There was a
      positive correlation between the minimal defibrillation energy and the dominant
      frequency of chronic AF (rho = 0.414, P = 0.035). Thus, power spectral analysis
      of AF using the surface ECG is feasible and may be useful in predicting the
      minimal shock energy required for successful cardioversion of chronic AF.

PMID- 12520677
TI  - Bleeding and thromboembolic risks of internal cardioversion for persistent atrial
      fibrillation.
AB  - Although internal cardioversion is an effective method for converting AF the
      thromboembolic risk and bleeding complication of this procedure remains unclear.
      Retrospective analysis of the thromboembolic events and bleeding complications
      was performed in 114 consecutive patients (mean age 63 +/- 10 years, 91 men) who
      underwent internal cardioversion for persistent AF (mean AF duration 31 +/- 42
      months). All patients received therapeutic warfarin for 3 weeks prior to the
      procedure, which was then replaced by periprocedural heparin therapy during
      internal cardioversion. The mean INR value before the internal cardioversion was
      1.3 +/- 0.2. A total of 992 R wave synchronized shocks were delivered (mean 8.7
      shocks/patients) without ventricular proarrhythmia. Successful internal
      cardioversion of AF was achieved in 100 (88%) patients. Two (2%) patients
      developed major bleeding complications with pericardial effusion after the
      procedure. Both of them subsided with conservative treatment. Minor bleeding with
      wound hematoma occurred in 8 (7%) of 114 after the procedure. Overall, there was
      no significant difference in the risk of procedure related complication between
      the use of heparin infusion and subcutaneous LMWH injection (6/78 [13%] vs 3/36
      [8%], P = 0.9). No thromboembolic event was observed after 4 weeks of follow-up.
      In conclusion, the risk of thromboembolism after discontinuation of
      anticoagulation before the procedure is low in patients with persistent AF
      underwent internal cardioversion. However, the use of periprocedural heparin
      therapy was associated with an increase risk of procedure related bleeding
      complications.

PMID- 12520678
TI  - The reliable electrocardiographic diagnosis of regular broad complex tachycardia:
      a holy grail that will forever elude the clinician's grasp?
AB  - The reliable and accurate diagnosis of regular broad complex tachycardia (BCT) by
      the ECG is a goal that has eluded clinicians and electrophysiologists alike for
      years. This article explores the reason for this by first giving an historical
      account on the development of the subject. Next, the electrophysiological
      mechanisms of ventricular tachycardia, supraventricular tachycardia with aberrant
      conduction, and preexcited tachycardia, the three main differential diagnoses for
      regular BCT, according to the latest knowledge from cellular and clinical
      electrophysiology study will be reviewed, together with considerations on how
      such understanding may help account for the manifestations of these tachycardias
      on the ECG and the difficulty in distinguishing between them. Finally, the use of
      electrophysiological study as the criterion standard for diagnosing regular BCT,
      as has been the case in most studies on the subject, will be critiqued in terms
      of the potential for misdiagnosis by the method and the use of any ECG diagnostic
      algorithms developed with its aid in the acute medical care setting.

PMID- 12520679
TI  - Electrocardiograms from the turtle to the elephant that illustrate interesting
      physiological phenomena.
AB  - This article describes a collection of ECGs from many species obtained over the
      past 50 years. Presented are ECGs of species in which the pacemaker is a separate
      contractile chamber with its own action and recovery potentials. In such species,
      pacemaker atrial and AV block can be produced. Shortening of the atrial
      refractory period and the negative inotropic effect can be produced by vagal
      stimulation. The cardiac electrogram and stroke volume are recorded from the
      turtle heart. The ECG and respiration were recorded from the snake. ECG records
      were obtained from the anesthetized and decapitated housefly. ECG records of the
      rabbit show slowing when the nose encountered irritating vapors. Records from a
      dog with atrial fibrillation exhibit rhythmic fibrillation frequency changes
      correlated with respiration. In addition, in a morphinized dog with atrial
      fibrillation, impulses crossed the AV node only during inspiration. The ECGs of a
      cow and camel exhibit long P-R intervals and biphasic P waves. Finally the
      elephant ECG shows a clear U wave following the T wave.

PMID- 12520680
TI  - An unusual bigeminal pattern: what is the mechanism?

PMID- 12520682
TI  - Radiofrequency catheter ablation of atypical atrial flutter masquerading as
      atrial fibrillation.
AB  - A patient with a surgically repaired double outlet right ventricle developed AF 6
      months after successful RF catheter ablation of typical atrial flutter. Guided by
      a 64-electrode basket catheter, the patient's AF was found to be dependent on an
      atypical atrial flutter circuit rotating around the fossa ovalis. Successful RF
      catheter ablation was performed by creating a line of conduction block from the
      superior vena cava to the fossa ovalis.

PMID- 12520681
TI  - Split atrial electrograms recorded during dual chamber pacing.
AB  - Split atrial electrograms (AEGs), as a measure of intraatrial conduction delay,
      have been previously identified during electrophysiological studies and as such,
      may be related to the development of atrial tachyarrhythmias. This article
      reports the finding of split AEGs observed in two patients with implanted dual
      chamber pacemakers. The event marker and the surface electrogram identified these
      AEGs by using and interpreting the intracardiac AEG derived from the atrial
      pacing lead.

PMID- 12520683
TI  - Treatment of superior vena caval obstruction following permanent pacemaker
      extraction.
AB  - Superior vena caval (SVC) obstruction following permanent pacemaker lead
      extraction is a serious but uncommon complication. This report describes the case
      of an 83-year-old man treated by balloon angioplasty and femoral pacemaker
      implantation.

PMID- 12520684
TI  - Permanent transfemoral pacemaker implantation in a child with Maroteaux Lamy
      syndrome.
AB  - Permanent transfemoral pacing has been described as an alternative route in
      patients in whom the superior venous approach is not feasible. This report
      describes the use of the femoral venous approach to insert a permanent pacemaker
      in a child with Maroteaux Lamy syndrome who has complete atrioventricular block
      and abnormal subclavian venous anatomy. Transfemoral pacing may be a suitable
      alternative in children with short stature.

PMID- 12520685
TI  - Bidirectional tachycardia eliminated with radiofrequency ablation.
AB  - This report describes an unusual case of bidirectional tachycardia eliminated
      with radiofrequency ablation. The tachycardia had alternating right and left
      bundle branch block morphology on a beat-to-beat basis and was successfully
      eliminated by ablating the right and left bundle branch block ventricular ectopic
      beats present during sinus rhythm.

PMID- 12520686
TI  - Cardiac vein angioplasty for biventricular pacing.
AB  - Biventricular pacing for the treatment of congestive heart failure has
      consistently demonstrated improvement in quality-of-life and reduction in heart
      failure symptoms. Though the over-the-wire systems will be helpful in overcoming
      many existing obstacles to optimal lead placement, anatomic variability will
      still limit overall success. Cardiac vein angioplasty may be required for
      deployment of leads into tortuous or obstructed cardiac veins. This case report
      describes the angioplasty of a focal cardiac vein stenosis allowing for
      successful implantation of a left ventricular pacing lead. The safety of this
      procedure is unknown, though the risks may be acceptable in certain patients.

PMID- 12520687
TI  - Right-sided prepectoral implantation of an implantable cardioverter defibrillator
      in a right pneumonectomized patient.
AB  - Right-sided prepectoral implantation of an ICD is performed in unusual
      circumstances only, like in patients with abnormal venous drainage and
      preexisting left-sided devices. This case report describes a 42-year-old man who
      had undergone previous right pneumonectomy and who required ICD implantation for
      symptomatic inducible nonsuppressable hemodynamically unstable ventricular
      tachycardia. To avoid the small but real possibility of inadvertent iatrogenic
      left-sided pneumothorax in a patient with previous right pneumonectomy, a dual
      chamber ICD with an active can was implanted in the right prepectoral position.

PMID- 12520688
TI  - Einthoven's first electrocardiogram 100 years ago.

PMID- 12520689
TI  - P wave over-sensing as a cause of ventricular asystole in a patient with a DDD
      pacemaker.

PMID- 12520690
TI  - Postpacemaker implant pericarditis: incidence and outcomes with active-fixation
      leads.

PMID- 12520691
TI  - Diagnosis of invasive mold infection. Is PCR the answer?

PMID- 12520692
TI  - On the use of quantitative modeling to help understand prostate-specific antigen
      dynamics and other medical problems.

PMID- 12520693
TI  - Toward complete and accurate reporting of studies of diagnostic accuracy. The
      STARD initiative.
AB  - Our objective was to improve the accuracy and completeness of reporting of
      studies of diagnostic accuracy, to allow readers to assess the potential for bias
      in the study, and to evaluate its generalizability. The Standards for Reporting
      of Diagnostic Accuracy Steering Committee searched the literature to identify
      publications on the appropriate conduct and reporting of diagnostic studies and
      extracted potential items into an extensive list. Researchers, editors, and
      members of professional organizations shortened this list during a 2-day
      consensus meeting with the goal of developing a checklist and a generic flow
      diagram for studies of diagnostic accuracy. The search for published guidelines
      regarding diagnostic research yielded 33 previously published checklists, from
      which we extracted a list of 75 potential items. At the consensus meeting,
      participants shortened the list to a 25-item checklist, using evidence whenever
      available. A prototypical flow diagram provides information about the method of
      patient recruitment, the order of test execution, and the numbers of patients
      undergoing the test under evaluation, the reference standard, or both. Evaluation
      of research depends on complete and accurate reporting. If medical journals adopt
      the checklist and the flow diagram, the quality of reporting of studies of
      diagnostic accuracy should improve, to the advantage of clinicians, researchers,
      reviewers, journals, and the public.

PMID- 12520694
TI  - The integration of molecular diagnostics with therapeutics. Implications for drug
      development and pathology practice.
AB  - It is widely anticipated that during the next 5 years the molecular diagnostic
      industry will continue to grow at double-digit pace to meet increasing demand for
      personalized medicine. A wide variety of drugs in late preclinical and early
      clinical development are being targeted to disease-specific gene and protein
      defects that will require coapproval of diagnostic and therapeutic products by
      regulatory agencies. An increasingly educated public will demand more information
      about their predisposition for serious diseases and how these potential illnesses
      can be detected in an early stage when they can be arrested or cured with new
      therapies custom-designed for their individual clinical status. To respond to
      this demand, major pharmaceutical companies will partner with diagnostics
      companies or develop their own in-house capabilities that will permit efficient
      production of more effective and less toxic integrated personalized medicine drug
      and test products. For clinical laboratories and pathologists, this integration
      of diagnostics and therapeutics represents a major new opportunity to emerge as
      leaders of the new medicine, guiding the selection, dosage, route of
      administration, and multidrug combinations and producing increased efficacy and
      reduced toxicity of pharmaceutical products.

PMID- 12520695
TI  - Diagnosis of invasive mold infection by real-time quantitative PCR.
AB  - We report the design and evaluation of a quantitative real-time polymerase chain
      reaction (PCR) assay to diagnose invasive mold infection (IMI) by detecting mold
      DNA in the serum. This assay detected 200 fg to 20 ng (5-log range) mold DNA and
      permitted a cutoff of 110 fg (3 genomes). Human or candidal DNA was not
      amplified. Specificity also was demonstrated by negative results in all 35
      patients (76 serum samples) with unlikely IMI at the cutoff. For patients with
      possible, probable, and documented IMI diagnosed by a combination of clinical,
      microbiologic, and histologic criteria, this real-time PCR showed positivity in
      40% (12/30), 68% (19/28), and 85% (11/13) cases, respectively, in testing of
      multiple serum samples. The overall serum positivity rate for these patients was
      15.1% (73/483). Quantitative analysis of the positive serum samples estimated the
      bodily circulating mold burden to be 1.6 x 10(5) genomes (5.3 ng) by geometric
      mean with 4.2 x 10(7) genomes (1,400 ng) the highest. These results suggest that
      for the diagnosis of IMI, this real-time PCR may be a promising alternative to
      other invasive methods. Further evaluation is underway.

PMID- 12520696
TI  - Clinical usefulness of components of the Triage immunoassay, enzyme immunoassay
      for toxins A and B, and cytotoxin B tissue culture assay for the diagnosis of
      Clostridium difficile diarrhea.
AB  - We studied 557 nonduplicate fresh stool specimens from adult patients clinically
      suspected of having Clostridium difficile-associated diarrhea. All samples were
      tested in parallel with an in-house cytotoxin B tissue culture assay (CTA), the C
      DIFFICILE TOX A/B II test (TA/B; TechLab, Blacksburg, VA), and the Triage Micro C
      DIFFICILE Panel (Biosite Diagnostics, San Diego, CA). The Triage device detects
      toxin A (TA) and glutamate dehydrogenase (GDH) simultaneously. Of the specimens,
      350 were negative and 95 were positive for all markers. Another 112 specimens
      yielded discrepant results. The CTA found 143 positive specimens. Results of the
      components of the Triage and TA/B were compared separately with those of CTA. GDH
      was the most sensitive but least specific marker, whereas TA and TA/B were less
      sensitive but highly specific. Because of these attributes and a quick turnaround
      time, GDH would be the best screening test for C difficile-associated diarrhea.
      CTA detected the highest number of cases of C difficile-associated diarrhea and
      would be most useful as a confirmatory test for GDH-positive and TA-negative
      specimens.

PMID- 12520697
TI  - Activated protein C resistance assay detects thrombotic risk factors other than
      factor V Leiden.
AB  - Activated protein C (APC) resistance is a common risk factor for venous
      thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden
      (FVL) polymorphism. FVL is considered responsible for up to 95% of APC
      resistance; however, other factor V polymorphisms and elevated factor VIII levels
      also have been implicated. We assessed whether additional mechanisms contribute
      to APC resistance in a blinded case-control study of 65 subjects by measuring APC
      resistance using 3 methods: 2 activated partial thromboplastin time-based methods
      with and without dilution in factor V-deficient plasma and 1 Russell viper venom
      based assay (RVV). Without factor V-deficient plasma, 24 subjects were APC
      resistant; with factor V-deficient plasma, the assay identified fewer APC
      resistant subjects, as did RVV. All assays detected the 7 heterozygous FVL
      subjects. Thirteen subjects had factor VIII levels above 150% (1.50). After
      excluding subjects with FVL or elevated factor VIII levels, 4 subjects still had
      APC resistance. VTE risk trended higher for subjects with APC resistance in the
      absence of FVL. Measurement of APC resistance without dilution in factor V
      deficient plasma is needed to assess for potentially important thrombotic risk
      factors other than FVL.

PMID- 12520698
TI  - Clinical significance of a borderline titer in a negative ELISA test for heparin
      induced thrombocytopenia.
AB  - We studied the usefulness of repeated enzyme-linked immunosorbent assay testing
      for heparin-induced thrombocytopenia (HIT) when the initial test result was
      negative and sought to determine whether the titer of the initial negative result
      correlated with the likelihood of obtaining a positive test result in repeated
      testing. We divided 150 patients who underwent HIT testing into 3 groups (50
      patients each): (1) very low titer negative (0.0%-33.3% of the threshold for a
      positive test); (2) low titer negative (33.4%-66.6% of the threshold); and (3)
      high titer negative (66.7%-99.9% of the threshold). Among the patients who
      underwent a repeat test, 5% (1/20) of group 1 patients, 13% (4/32) of group 2
      patients, and 43% (13/30) of group 3 patients tested positive in the repeat test
      (P = .0026). Thus, nearly half of patients with initially negative HIT test
      results had positive results in the repeat test if the negative titer was 66.7%
      or more of the threshold. If laboratories report the HIT titer, rather than just
      negative or positive, the titer might help clinicians predict which patients have
      HIT despite a negative initial test, and the overall sensitivity for diagnosing
      HIT might be improved.

PMID- 12520699
TI  - The effect of lupus anticoagulant in the second-generation assay for activated
      protein C resistance.
AB  - The activated protein C resistance (APCR) assay is the test of choice to screen
      for factor V Leiden. We evaluated the effect of lupus anticoagulant on the
      baseline clotting time of the second-generation APCR assay with plasma samples
      from 54 patients to determine whether a falsely low APCR ratio could be
      predicted. We also assessed whether a modification of the assay could make it
      more reliable in the presence of strong lupus anticoagulants. Of 54 plasma
      samples, 5 yielded a false-positive APCR ratio, and all 5 had a prolonged
      baseline clotting time. Further dilution (1:40) of the plasma samples in factor V
      deficient plasma led to correction of the APCR ratio and did not affect the
      sensitivity of the test for factor V Leiden. Our data support that the baseline
      clotting time is a good predictor of a false-positive APCR test result and should
      be checked before calculating the ratio. The modified APCR assay reliably
      identified the false-positive ratios and could be used to screen for factor V
      Leiden in samples with strong lupus anticoagulant.

PMID- 12520700
TI  - Fetal-maternal hemorrhage detection in Ontario.
AB  - The results from fetal-maternal hemorrhage (FMH) detection and quantitation
      external quality assessment surveys conducted in Ontario indicate that the
      rosette test had a sensitivity and specificity for an FMH of more than 10 mL of
      1.0 and 0.75, respectively, compared with 0.96 and 0.92, respectively, for acid
      elution. With FMH quantitation, the percentage error of the mean from the target
      FMH was 20% or more in 7 of 8 surveys, and coefficients of variation ranged from
      39.5% to 71.8%. Inadequate Rho(D) immune globulin prophylaxis could have occurred
      in 19.4% of the challenges with an FMH of more than 10 mL. The rosette and acid
      elution techniques are both effective for the detection or exclusion of FMH, but
      acid elution lacks adequate accuracy and precision for reliable FMH quantitation.
      Furthermore, a strategy of prescribing an extra 1,500-IU Rho(D) immune globulin
      dose, in addition to the dose required to treat the volume of fetal blood
      detected, is an effective strategy to overcome the limitations of FMH
      quantitation by acid elution.

PMID- 12520701
TI  - Tumor volume in prostate cancer and serum prostate-specific antigen. Analysis
      from a kinetic viewpoint.
AB  - Many have observed poor correlations between serum prostate-specific antigen
      (PSA) and tumor volume, and this noise undoubtedly reduces the diagnostic
      specificity of PSA. To explore this phenomenon, we addressed the problem from a
      theoretical viewpoint. Specifically, we used a compartmental model and first
      order kinetics to develop the mathematics necessary to relate serum PSA to tumor
      volume. We found that the resulting model fit well the observed kinetic data of
      PSA measured after biopsy or prostatectomy. The model also predicted a linear
      relationship between PSA and the sum of volumes of benign and malignant tissues,
      but the coefficients for this linear equation are more complex than previously
      thought. They reflect not only how much PSA may be present in each tissue but
      also 3 rate parameters and the volume of serum. Much of the noise in the linkage
      between PSA and tumor volume is due to individual patient differences in the 3
      rate parameters and in serum volume. Our model predicts that without ways to
      directly measure the several involved rate parameters, we will not be able to
      accurately predict tumor volume from PSA. Nevertheless, surrogates for the
      missing parameters may exist and could lead to statistical models that could
      improve the prediction of tumor volume.

PMID- 12520702
TI  - Non-tumor-associated psammoma bodies in the thyroid.
AB  - Psammoma bodies in the thyroid are common in glands with papillary thyroid
      carcinoma. Psammoma bodies that are not associated with tumor cells, however,
      represent a diagnostic problem for pathologists. Should we treat isolated
      psammoma bodies as representing metastatic disease? This study included patients
      who had non-tumor-associated psammoma bodies in their thyroids or in the
      perithyroidal lymph nodes. Clinical, pathologic, and follow-up information was
      obtained for the patients. Our results indicate that 27 of 29 patients had a
      contralateral or an ipsilateral tumor, the majority of which were papillary. We
      noted a high frequency of microscopic carcinomas (12/27) and of tall cell
      variants of papillary thyroid carcinoma (8/27 cases). Based on these findings, we
      recommend that thyroid glands with non-tumor-associated psammoma bodies and no
      histologically identified carcinoma be entirely submitted to identify any
      microscopic carcinoma. If no carcinoma is identified in a lobectomy, discussion
      with the surgeon should indicate the need for close clinical follow-up.

PMID- 12520703
TI  - Detection of extrahepatic hepatitis C virus replication by a novel, highly
      sensitive, single-tube nested polymerase chain reaction.
AB  - We established a cell culture system for the replication of hepatitis C virus
      (HCV) by using human T and B leukemia cell lines. These 2 cell lines were
      infected in vitro by using HCV-positive pooled patient serum samples. HCV RNA was
      extracted from infected cell lines at different times after infection, and a
      sequence of the virus 5' untranslated region was analyzed. Hepatitis C minus
      strand RNA was detected in the infected cell lines by highly strand-specific rTth
      (recombinant Thermus thermophilus DNA polymerase)-based reverse transcription
      followed by a novel, highly sensitive, single-tube nested polymerase chain
      reaction (PCR) method. PCR products were analyzed by direct DNA sequencing. These
      results indicate that the HCV can replicate in T and B lymphocytes. This model
      should represent a valuable tool for the detailed study of the initial steps of
      the HCV replication cycle and for the evaluation of antiviral molecules.

PMID- 12520704
TI  - Infiltration of Helicobacter pylori in the gastric mucosa.
AB  - It is our hypothesis that if Helicobacter pylori could be demonstrated
      conclusively to have transgressed the mucosal surface into the lamina propria,
      this would help explain how H pylori recruits inflammatory cells. We report our
      immunohistochemical and electron microscopic findings that demonstrate that H
      pylori can be detected in the lamina propria of the stomach, offering evidence of
      its invasive potential. We stained 67 endoscopic gastric biopsy specimens with
      Warthin-Starry silver and immunoperoxidase stains for H pylori. In addition,
      transmission electron microscopy was performed on 1 case. The presence of surface
      H pylori was associated significantly with active (P < .0001) and chronic (P <
      .0001) inflammation. H pylori could not be identified in the lamina propria using
      the Warthin-Starry silver stain alone. Immunoreactivity for H pylori in the
      lamina propria was detected in 20 (30%) of 67 gastric biopsy specimens.
      Transmission electron microscopy confirmed the immunohistochemical findings. H
      pylori can infiltrate the lamina propria of the gastric mucosa, thereby proving
      morphologic evidence of its invasive capability.

PMID- 12520705
TI  - Peritoneal involvement in stage II colon cancer.
AB  - A pathologist (K.S.) reviewed histologic slides for peritoneal involvement by
      tumor cells for 118 patients with stage II colon cancer. Patients were followed
      up for a median of 6 years. Tumor cells were found free in the peritoneal space
      in 16 cases (13.6%). The presence of cancer cells free in the peritoneal space
      was associated with lymphovascular invasion (P = .001) and neural invasion (P <
      .001). The overall 5-year survival was 80% in the patient population, but was 39%
      and 86% for those with and without tumor cells free in the peritoneal space,
      respectively (P < .0001). Multivariate analysis confirmed that free tumor cells
      within the peritoneal space (P < .0001) and lymphovascular invasion (P = .007)
      were related independently to outcome. Peritoneal involvement with tumor cells
      free in the peritoneal space in stage II colon cancer is a powerful indicator of
      outcome; patients have a survival similar to that for patients with stage III
      disease.

PMID- 12520706
TI  - The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin,
      lung, muscle, and kidney.
AB  - Although the histologic characteristics of cryofibrinogenemia have been described
      in skin lesions, the literature is largely devoid of descriptions of this
      disorder in other organs. This series is the first to document the
      histopathologic manifestations of intrapulmonary, intramuscular, and renal
      cryofibrinogenemia. We describe the histopathologic manifestations of
      cryofibrinogenemia in 10 cases with manifestations in 4 organ systems: skin in 7
      cases, skeletal muscle in 2, lung in 2, and kidney in 1. Irrespective of anatomic
      site, all lesions showed an occlusive thrombotic diathesis comprising
      eosinophilic refractile deposits within vessel lumina with extension into the
      intima, with or without an accompanying characteristic granulomatous vasculitic
      component. Ultrastructural examination of the renal deposits showed fibrillary
      material within glomerular capillary lumina with unique morphologic features not
      previously described. Analysis of plasma from several cases revealed a cold
      precipitable protein, which in most cases included a monoclonal paraprotein. The
      laboratory and histologic distinctions between cryofibrinogenemia and
      cryoglobulinemia are addressed. We provide guidelines for the proper handling of
      patient specimens in the workup of cryofibrinogenemia.

PMID- 12520707
TI  - Immunohistochemical expression of cathepsin D in meningiomas.
AB  - We retrospectively studied the expression of cathepsin D by immunohistochemical
      analysis in 86 meningiomas (World Health Organization [WHO] grade I, n = 44; WHO
      grade II, n = 21; WHO grade III, n = 21) and correlated the results with tumor
      grade and outcome. Staining was scored semiquantitatively based on distribution
      among neoplastic cells as follows: 0, no staining; 1+, 5% or less of the cells;
      2+, 6% to 20%; 3+, 21% to 50%; and 4+, more than 50% of the cells. Cathepsin D
      expression was observed as follows: 0, 10 cases (12%); 1+, 25 cases (29%); 2+, 15
      cases (17%); 3+, 12 cases (14%); and 4+, 24 cases (28%). A higher degree of
      cathepsin D immunostaining was associated with low tumor grade (P = .0014), low
      mitotic count (P < .0001), low apoptotic count (P < .0001), and the development
      of recurrence (P = .035). There was no correlation with outcome or MIB-1
      proliferation index. Cathepsin D expression by immunohistochemical analysis was
      identified in the majority (88% [76/86]) of meningiomas studied. A greater degree
      of immunoreactivity was observed in the WHO grade I group.

PMID- 12520708
TI  - Comparative analysis of light chain expression in germinal center cells and
      mantle cells of reactive lymphoid tissues. A four-color flow cytometric study.
AB  - We studied skewing of light chain ratios (LCRs) in germinal center cells (GCCs)
      relative to mantle cells (MCs) by flow cytometry (FC) in 98 reactive lymphoid
      tissues. LCRs were assessed using a 4-color lambda/kappa/CD20/CD38 tube. GCCs and
      MCs were discriminated by CD20 and CD38 density. Of 98 cases, 65 contained
      distinct GCCs and MCs. Light chain expression usually was dimmer on GCCs than on
      MCs; in 22 cases, the kappa and lambda clusters converged and accurate LCRs could
      not be determined. Of the remaining 43 cases, the mean GCC LCR was 1.78 (range,
      1.10-3.07) vs 1.56 (range, 1.00-2.24) in the MCs (P = .001). The overall
      kappa/lambda ratio in cases containing GCCs and MCs was 1.65 (range, 1.18-2.69)
      compared with 1.46 (range, 1.00-1.98) in cases containing MCs only. Of 43 cases,
      19 (44%) showed differences of 20% or more between the LCRs of GCCs and MCs. LCRs
      of GCCs and MCs may differ substantially in reactive lymphoid tissues. These
      subsets may form distinct clusters and skews in their LCRs and should not be
      misinterpreted as evidence of occult lymphoma.

PMID- 12520709
TI  - A novel method for the detection, quantitation, and breakpoint cluster region
      determination of t(15;17) fusion transcripts using a one-step real-time multiplex
      RT-PCR.
AB  - Individuals with acute promyelocytic leukemia (APL) usually express 1 of 3
      primary hybrid transcripts associated with a t(15;17). The 3 fusion transcripts
      are the result of heterogeneous breakpoint cluster regions (bcr) within the
      promyelocytic leukemia (PML) gene and are denoted bcr1 (long), bcr2 (variant),
      and bcr3 (short) forms. Many researchers have shown that real-time quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) of the involved
      transcript is a valuable tool for monitoring APL and its treatment. In addition,
      some research suggests that identification of a specific breakpoint region may be
      used to predict an individual's likelihood of relapse and possibly their response
      to all-trans retinoic acid treatment. We describe the first reported 1-step
      multiplex RT-PCR assay capable of t(15;17) fusion transcript real-time relative
      quantitation and simultaneous transcript form identification in 2 reactions. This
      assay uses a novel dual-probe technique to achieve what has required a laborious
      procedure of 2 or more reactions followed by postamplification analysis. We found
      a correlation of 100% in detection and breakpoint determination of the long,
      short, and variant forms with a breakpoint 5' to nucleotide 1709 compared with
      results from traditional methods.

PMID- 12520710
TI  - bcl-2 expression by multicolor flow cytometric analysis assists in the diagnosis
      of follicular lymphoma in lymph node and bone marrow.
AB  - The expression of bcl-2, CD10, and CD20 was examined by multicolor flow cytometry
      in 78 samples including lymph node or other tissue biopsy specimens containing
      follicular lymphoma (FL; n = 17), reactive hyperplasia (RH; n = 28), or other
      malignant lymphomas (n = 20), as well as bone marrow aspirates (n = 13). The
      presence of CD10+ cells with high bcl-2 expression predicted the presence of FL
      rather than RH with a positive predictive value of 100% and negative predictive
      value of 96%. CD10+ cells with high bcl-2 expression also were found in a subset
      of diffuse large B-cell lymphomas and were otherwise rare in other types of
      malignant lymphoma. In contrast with immunohistochemical studies, a reduced but
      apparently measurable level of bcl-2 was present in benign follicular center
      cells. Hematogones showed lower bcl-2 levels than did FL cells in the bone
      marrow, and neutrophils were bcl-2-. Measurement of bcl-2 expression levels by
      multiparameter flow cytometry offers a rapid, quantitative assessment that may
      assist in the diagnosis of FL in lymph nodes or bone marrow, even when other
      CD10+ cells or admixed normal B cells are present.

PMID- 12520712
TI  - We come bearing gifts.

PMID- 12520711
TI  - Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in
      sequential bone marrow biopsy specimens.
AB  - Although the new World Health Organization (WHO) classification acknowledges
      "prefibrotic" phases, progression of myelofibrosis in chronic idiopathic
      myelofibrosis (cIMF) is controversial because there are only a few studies about
      sequential biopsy specimens, and they yield conflicting results. The conflicting
      results might be due to a mixture of different degrees of myelofibrosis and
      therapy regimens within the respective groups studied. To prove this hypothesis,
      we studied sequential bone marrow biopsy specimens from patients with cIMF and
      compared 3 groups with different degrees of myelofibrosis at initial diagnosis
      with a group of patients with primarily unfibrosed disease who met the WHO
      criteria for prefibrotic cIMF. Patients receiving chemotherapy were considered
      separately from patients without treatment. Our results favor a steady
      progression of myelofibrosis unrelated to therapy modalities, whereas confusing
      literature data can be explained: fibrosis may remain static or lessen,
      especially in more advanced stages of cIMF.

PMID- 12520713
TI  - A voice to be heard in mental health.

PMID- 12520714
TI  - The consumer movement in mental health care.

PMID- 12520716
TI  - Self-cutting.

PMID- 12520715
TI  - When I am on medication, I cease to be myself: misgivings about taking
      antidepressants.

PMID- 12520717
TI  - On stigma in our society.

PMID- 12520718
TI  - "Madness"--is there madness?

PMID- 12520719
TI  - Childhood neglect and its effects a personal perspective.

PMID- 12520721
TI  - Living with a schizoid personality.

PMID- 12520720
TI  - The things that help one cope.

PMID- 12520722
TI  - The Internet as a means for promoting the recovery and empowerment of people with
      mental health problems.

PMID- 12520723
TI  - Living through the Yom Kippur war.

PMID- 12520724
TI  - The enclave of schizophrenia.

PMID- 12520725
TI  - [What is your diagnosis? Display of typical atrial flutter].

PMID- 12520726
TI  - [Hormone replacement and breast carcinoma].
AB  - This review discusses the effect of Oestrogens, Progestagens, Tibolone,
      Raloxifene and Phytooestrogens in postmenopausal women on the breast.
      Epidemiological statisticians are only speaking of a clinical significance if the
      relative risk is half (< 0.05) or doubled (> 2.0). All published data from
      observational studies or from important meta- and reanalyses concerning the
      relative risk of breast cancer in women using postmenopausal hormone therapy are
      within these limits and clearly below the risk observed in young smokers. The
      relative risk for breast cancer observed in the Womens Health Initiative (WHI)
      stays within these limits too, in women treated by a fix Oestrogen-Progestagen
      combination. However, in the WHI, there was no increase of the relative risk for
      breast cancer in women using oestrogens alone. The risk for breast cancer rises
      in parallel to the duration of the hormone treatment. The risk for hormone users
      to suffer from breast cancer does not increase earlier than 4-5 years after the
      start of the therapy. An important reanalysis reports, that after 5 years of
      hormone use, a breast cancer is diagnosed in 2 additional women out of 1000 (47
      instead of 45 women). The absolute risk should be indicated in addition to the
      relative risk because, for non-specialists, the exclusive indication of the
      relative risk might be misleading. Following the results from the WHI and from
      some other, older studies, the relative risk for breast cancer might be higher in
      women taking an oestrogen-progestagen combination than in women using oestrogens
      alone. Experimental and preliminary clinical data on Tibolone and Raloxifene do
      not show a negative effect on breast tissue. However, if Tibolone and Raloxifene
      as well as Phytooestrogens possess a protective activity remains open because
      prospective randomized long-term clinical studies are still missing.

PMID- 12520727
TI  - [Schizophrenia, diabetes and new neuroleptics].
AB  - Diabetes mellitus occurs more frequently in schizophrenic patients. The use of a
      novel antipsychotic drug seems to be concomitant to a further increase in
      imbalance of blood glucose homeostasis. Such cases have already been reported in
      the literature indicating that diabetes mellitus might be a real side effect of
      this novel class of neuroleptics. In conclusion, it seems that schizophrenic
      patients under such treatment would greatly benefit from a closer clinical and
      biological follow up regarding glucose metabolism. Further randomised studies
      would be needed.

PMID- 12520728
TI  - [Methods for treating children with newly diagnosed idiopathic thrombocytopenic
      purpura--evidence versus opinion based medicine].

PMID- 12520729
TI  - [20-year-old patient with unilateral headache. Migraine with aura].

PMID- 12520730
TI  - [Hypophyseal hyperplasia in primary hypothyroidism].

PMID- 12520731
TI  - [Molecular mechanism of inhibition of sodium butyrate on activation of tumor
      associated aromatase promoters].
AB  - BACKGROUND & OBJECTIVE: Sodium butyrate, a histone deacetylase inhibitor, can
      inhibit tumor conditioned medium-induced levels of promoter II and I. 3-specific
      transcripts. This study was designed to investigate the action of sodium butyrate
      on promoter II and I. 3 activity, which can be directed to elucidation of local
      estrogen production in breast cancer. METHODS: Primary human adipose fibroblasts
      (HAF) treated with MCF-7 breast cancer cell-conditioned medium were used as a
      cell model system. Promoter II and I. 3 deletion luciferase constructs was
      transfected into HAF. Western blotting and electrophoretic mobility shift assay
      were performed to evaluate the effect of sodium butyrate on promoter II and I .3.
      RESULTS: Breast cancer cell-conditioned medium enhanced phosphorylation of
      activator transcription factor-2 (ATF-2) which was the main modulatory subtype in
      CREB/ATF-2 family. The effect of sodium butyrate on aromatase expression in
      breast tumor fibroblasts was mediated by inhibition of phosphorylation of ATF-2,
      and hence, the inhibition of binding of a transcriptional complex containing
      phosphorylated ATF-2, C/EBP beta and CREB binding protein (CBP) to promoter II/I.
      3 regulatory region. CONCLUSIONS: Sodium butyrate reduces the level of aromatase
      mRNA arising from cancer-induced promoter region. The aberrant activation of
      promoter II and I. 3 in HAF is dependent on the phosphorylation of ATF-2.

PMID- 12520733
TI  - [Effects of matrine on the activity of protein tyrosine kinase and phosphatase in
      K562 cells].
AB  - BACKGROUND & OBJECTIVE: The differentiation of K562 cells can be induced by a
      given concentration of matrine. This study was designed to investigate the
      mechanism of signal transduction in induced differentiation of K562 cells.
      METHODS: ELISA coupled with streptavidin-biotin system was used to dynamically
      detect the activity of protein tyrosine kinase and phosphatase in the cytoplasm
      and the membrane of K562 cells treated by matrine. RESULTS: Matrine inhibited the
      activity of protein tyrosine kinase in K562 cells, and the inhibitive effect
      depended on matrine of the concentration within 0.1 mg/ml. The effects of
      different concentration of matrine on the protein tyrosine phosphatase activity
      had no significant difference. Activity of the protein tyrosine phosphatase
      decreased transiently accompanied with the activity of the protein tyrosine
      kinase in K562 cells treated with 0.1 mg/ml matrine. CONCLUSIONS: The change of
      protein tyrosine kinase activity is involved in the differentiation of K562 cells
      induced by matrine. The tyrosine kinase activity in cell membrane decreased more
      rapidly than that in cell cytoplasm, suggesting there be a transmembrane signal
      transduction. The change of tyrosine phosphatase activity following the kinase
      indicates the real time regulation of phosphorylation and dephosphorylation.
      Moreover, the inhibitory effect of matrine on the protein tyrosine kinase shows
      the characters of specificity and saturation, suggesting the exist of matrine
      associated receptor in K562 cells.

PMID- 12520732
TI  - [Relationship between expression of apoptosis-associated proteins and caspase-3
      activity in cisplatin-resistant human ovarian cancer cell line].
AB  - BACKGROUND & OBJECTIVE: Cisplatin-based chemotherapy is an important way for
      treatment of ovarian cancer, but resistance to cisplatin is one of the reasons of
      treatment failure of ovarian cancer. This study was designed to investigate the
      relationship between apoptosis-associated proteins and caspase-3 activity as well
      as their effects on chemoresistance in human ovarian cancer cell lines. METHODS:
      The expression of apoptosis-associated proteins (bcl-2, bcl-xL, bax, bcl-xs), the
      activity of caspase-3 and cleavage of poly ADP-ribose polymerase (PARP) were
      determined with Western blot analysis in the cisplatin-resistant cell (COC1/DDP)
      and cisplatin-sensitive human ovarian cancer cell (COC1). The apoptotic ratios of
      COC1 and COC1/DDP were measured with flow cytometry after treated with different
      concentration of cisplatin. RESULTS: The expression of bcl-2 and bcl-XL in
      COC1/DDP cell was significantly higher than that in COC1 cell, whereas the
      expression of bax showed no change in COC1/DDP and COC1. There was no bcl-xs
      expression in both COC1 and COC1/DDP cells. The activity of caspase-3, the amount
      of PARP fragments, and apoptotic ratio in COC1/DDP reduced much more than COC1
      did after treated with cisplatin. CONCLUSIONS: Cisplatin-resistance in human
      ovarian cancer cell lines may associated with the overexpression of anti
      apoptotic protein bcl-2 and downregulation of caspase-3 activity, but not
      associated with the expression of bax and bcl-xs.

PMID- 12520734
TI  - [Inhibitory effects of curcumin on apoptosis of human ovary cancer cell line
      A2780 and its molecular mechanism].
AB  - BACKGROUND & OBJECTIVE: Curcumin is the major effective component of curcuma,
      which is a kind of traditional Chinese medicine. It has been paid more attention
      to curcumin recently for its specific proliferation inhibition and apoptosis
      inducing effects on tumor cells; however, the involved mechanisms were not clear.
      This study was designed to explore the apoptosis inducing effects of curcumin on
      human ovary A2780 cell line and its related molecular mechanisms. METHODS: A2780
      cancer cells were treated with 10-50 mumol/L curcumin for 6-24 h and the growth
      inhibition rates of A2780 cancer cells were measured by MTT method. Cell
      apoptosis was inspected by flow cytometry (FCM) and acridine orange-ethidium
      bromide fluorescent staining method. The protein levels of NF-kappa B (P65) and
      Caspase-3 in cancer cells were observed by SP immunohistochemistry. RESULTS: The
      growth inhibition rates of the cancer cells reached 62.05%-89.24%, with the peak
      of sub G1 appeared on DNA histogram in FCM. Partial cells presented the
      characteristic morphological changes of apoptosis under the fluorescent
      microscope; the apoptosis rates were 21.5%-33.5%. The NF-kappa B (p65) expression
      was decreased while Caspase-3 expression was increased, which depended on the
      action time. CONCLUSIONS: Curcumin could significantly inhibit the growth of
      ovary cancer cells; inducing apoptosis through up-regulating Caspase-3 and down
      regulating expression of NF-kappa B was probably one of its molecular mechanisms.

PMID- 12520735
TI  - [Bcl-2 antisense oligodeoxynucleotide enhances araninosyl cytosine-induced
      apoptosis of primary leukemia cells].
AB  - BACKGROUND & OBJECTIVE: The previous study has identified two novel antisense
      oligonucleotides (AS-ODN) of new target point in the translation initiation and
      the coding region of bcl-2 mRNA that could increase the sensitivity of HL-60 and
      K562 cells lines to etoposide, daunorubicin, and araninosyl cytosine (Ara-C).
      This study was designed to investigate whether the two novel bcl-2 AS-ODNs could
      increase Ara-C-induced apoptosis of cultured primary acute leukemia (AL) and
      chronic lymphocytic leukemia (CLL) Cells. METHODS: Cell surviving fraction was
      determined using the trypan blue dye exclusion assay. The expression levels of
      bcl-2 protein were assayed by immunofluorescence using fluorescein isothiocyanate
      label. Apoptosis was detected by Giemsa staining and flow cytometry. RESULTS:
      Treatment with the two AS-ODNs/Ara-C combination respectively for 48 h
      significantly inhibited the growth of AL and CLL cells. There was significant
      difference on AL and CLL cells survival between nonsense oligodeoxynucleotide(NS
      ODN)/Ara-C combination and Ara-C treated cells alone (P < 0.05). It was found
      that the two AS-ODNs respectively combined with Ara-C could significantly
      downregulate bcl-2 protein expression (P < 0.05). There was a significant
      increase in apoptotic rates of AL or CLL cells after treatment with the two AS
      ODNs respectively combined with Ara-C as respectively compared with the NS
      ODN/Ara-C combination and Ara-C treated cells alone; and the effect had
      statistical difference (P < 0.05). Compared to the AS-ODN directed against the
      translation initiation of bcl-2 mRNA, the AS-ODN directed against the coding
      region showed stronger effect in the aspects of increasing the sensitivity of AL
      cells to Ara-C (P < 0.05). CONCLUSIONS: The two novel AS-ODNs of new target point
      in the translation initiation and the coding region of bcl-2 mRNA could enhance
      Ara-C induced apoptosis of AL and CLL cells.

PMID- 12520736
TI  - [Preliminary study of apoptosis of human hepatocarcinoma cell line HepG2 induced
      by topotecan].
AB  - BACKGROUND & OBJECTIVE: Topotecan, a semisynthetic water-soluble derivative of
      camptothecin, is a potent inhibitor of DNA topoisomerase I and cell cycle
      specific antitumor agent; The incidence rate of hepatocarcinoma ranks the third
      in all types of malignant tumor in China. The clinical curative effect of the
      present treatments and drugs for hepatocarcinoma are not so satisfactory. The
      inducing effect of topotecan on apoptosis of hepatocarcinoma cell line HepG2 and
      its cytotoxicity on HepG2 were studied in this paper. METHODS: Microculture
      tetrazolium assay (MTT), HE staining, transmission electron microscope (TEM),
      flow cytometer (FCM) and immunohistochemistry were employed to determine and
      observe the apoptosis of HepG2 induced by topotecan and its lethal action on
      HepG2. RESULTS: Topotecan killed HepG2 cell by inducing apoptosis. Topotecan had
      strong anti-HepG2 activity in vitro, suggesting distinct dose- and time-dependent
      relationship. The drug IC50 was about 95 micrograms/L. Topotecan block HepG2 in S
      phase, then further initiate apoptosis program. The morphologic characteristic of
      apoptosis showed that it is a typical interphase apoptosis process: the nuclei
      showed chromatin pycnosis, and clustered on the inner border of karyotheca,
      cytoplasm condensed, many vacuoles occurred in it. The expression of bcl-2 were
      not affected in the course of HepG2 apoptosis induced by topotecon (P > 0.05).
      CONCLUSION: Topotecan had significant cytotoxicity on HepG2 by inducing
      apoptosis.

PMID- 12520737
TI  - [Multidrug resistance mechanisms in cell line HL-60/VCR].
AB  - BACKGROUND & OBJECTIVE: Drug resistance is a major factor in chemotherapeutic
      failure of leukemia. Multidrug resistant cell lines are the good models for
      investigating the mechanisms and reversal of acquired drug resistance. This study
      was designed to explore the multidrug resistance (MDR) mechanisms in cell line HL
      60/VCR. METHODS: Flow cytometry and a panel of antibodies were used to analyze
      the expression of MDR proteins (P-gp, MRP, LRP, BCRP, GST-pi) and apoptosis
      modulating proteins (bcl-2, bcl-x, bax, bad) in MDR cell line HL-60/VCR and drug
      sensitive cell line HL-60. RESULTS: The expression levels of MDR proteins (P-gp,
      MRP, BCRP, GST-pi) were (18.62, 1.19, 1.50, 1.32-flod) higher in HL-60/VCR than
      in HL-60, while the expression of LRP level was similar. The levels of apoptosis
      modulating proteins(bcl-2, bcl-x, bad) were (2.48, 1.25, 1.08-fold) higher in HL
      60/VCR than in HL-60, while the pro-apoptosis protein bax contrarily decreased in
      HL-60/VCR. CONCLUSION: Various MDR mechanisms were involved in multi-drug
      resistance HL-60/VCR cell line, which including increasing expression of drug
      resistance protein (P-gp, MRP, BCRP, and GST-pi); the apoptosis-modulating
      proteins (bcl-2, bcl-x, bax, and bad) might take part in the mechanism of drug
      resistance.

PMID- 12520738
TI  - [Research of the anti-tumor effect of human endostatin mediated by recombinant
      adeno-associated virus].
AB  - BACKGROUND & OBJECTIVE: It was reported that endostatin could inhibit tumor
      angiogenesis, then inhibit the growth and metastasis of tumor. However, there was
      few report about the treatment usage of endostatin. This study was designed to
      explore the effect of endostatin mediated with recombinant adeno-associated
      virus(rAAV) on tumor growth and metastasis. METHODS: To obtain the endostatin
      gene complete cDNA by RT-PCR, and clone it into the plasmid pSNAV and package the
      recombinant rAAV-SS-endostatin; to analyze its anti-tumor effect through animal
      experiments. RESULTS: In the B16F10 melanoma tumor model, C57BL/6 mice were
      inoculated with 10(11)TU rAAV-SS-endostatin i.m. injection, which the inhibition
      rate was 57.1%; In the lung metastatic model, the inhibition rate of metastases
      was 70.7%. CONCLUSIONS: rAAV-SS-endostatin can effectively inhibit tumor growth
      and metastasis.

PMID- 12520739
TI  - [Inhibitory effects of TNP-470 in combination with 5-fluorouracil on growth of
      human colon cancer].
AB  - BACKGROUND & OBJECTIVE: Neovascularization is critical for growth of primary
      tumors and their distant metastasis. This study was designed to investigate the
      effects of angiogenesis inhibitor TNP-470 in combination with 5-fluorouracil (5
      FU) on the growth of human colon cancer cell line, LOVO, in vitro and in vivo.
      METHODS: In vitro, the growth inhibitory effect of TNP-470 or 5-FU on LOVO cells
      was examined by MTT assay, and synergetic effect of these two agents was
      evaluated by Burgi analysis. In vivo, human colon cancer xenografts were
      transplanted into BALB/C nude mice and treated with TNP-470 alone and combination
      with 5-FU. Tumor microvessel density (MVD) was measured by immunostaining with
      anti-von Willebrand factor monoclonal antibody; the expression of vascular
      endothelial growth factor (VEGF) in tumor tissue was detected using an
      immunohistochemical method with image analysis system. RESULTS: In vitro, TNP-470
      and 5-FU inhibited the growth of LOVO cells, with the IC50 at 55.8 ng/ml and 4.6
      ng/ml, respectively. Burgi analysis revealed synergism of these two agents, a
      remarkable growth inhibitory effect on LOVO cells was obtained. In vivo, in every
      treatment group, tumor growth was suppressed significantly. The combination group
      showed significant enhancement in antitumor efficacy. Expression of VEGF in
      tumors was clearly inhibited by TNP-470 in combination with 5-FU or 5-FU alone
      compared to the control. Tumor MVD was lower in TNP-470 combination with 5-FU
      group or TNP-470 group compared to control group. CONCLUSION: TNP-470 suppressed
      the growth of LOVO cells and human colon cancer xenografts and the angiogenesis;
      TNP-470 in combination with 5-FU might product synergetic effect.

PMID- 12520740
TI  - [Combination of thalidomide and rituximab in suppressing myeloma cells in vitro].
AB  - BACKGROUND & OBJECTIVES: The efficiency of rituximab (Mabthera) is related to
      CD20 expression density on cell membrane. It is not yet to be solved how to
      heighten expression level of CD20 on multiple myeloma (MM) cell membrane and to
      increase the efficacy of Mabthera to MM. This study was designed to observe
      whether thalidomide could promote the effect of Mabthera on suppressing myeloma
      cells in vitro and its possible mechanism. METHODS: Colony growth of 18 untreated
      and 20 relapsed or refractory MM patients' myeloma cells were observed in the
      methylcellulose semisolid medium adding thalidomide (10, 50, 75, 100, 150, 200,
      300 micrograms/ml) or Mabthera (0.5, 1, 2, 4, 8, 12, 16 micrograms/ml) or
      thalidomide above 7 doses in combination with Mabthera of 16 micrograms/ml or
      Mabthera above 7 doses in combination with thalidomide of 75 micrograms/ml.
      Change of CD20 expression on the myeloma cells were measured by flow cytometer
      after and before myeloma cells were treated with thalidomide. RESULTS: The
      inhibition of the colony formation of untreated MM patients' myeloma cells
      occurred in 1. use only of thalidomide at more than or equal to 75 micrograms/ml
      or use only of Mabthera at 16 micrograms/ml, 2. use of thalidomide at 75
      micrograms/ml with or without Mabthera at 16 micrograms/ml, 3. use of thalidomide
      at more than or equal to 75 micrograms/ml with or without Mabthera at 16
      micrograms/ml; The inhibition of the colony formation of relapsed or refractory
      MM patients' myeloma cells occurred in 1. use of thalidomide at 75 micrograms/ml
      with Mabthera at 16 micrograms/ml, 2. use of thalidomide at more than or equal to
      100 micrograms/ml with or without Mabthera at 16 micrograms/ml; Thalidomide at
      more than 75 micrograms/ml enhanced the expression of CD20 antigen in untreated
      and relapsed or refractory MM patients' myeloma cells. CONCLUSION: Thalidomide
      could enhance the inhibition of Mabthera on colony formation of MM patients'
      myeloma cells, which is related to that thalidomide enhances CD20 antigen
      expression of myeloma cells.

PMID- 12520741
TI  - [Treatment of spontaneous metastatic lung cancer with interleukin-12 gene
      modified dendritic cells vaccine].
AB  - BACKGROUND & OBJECTIVE: Although many works have been done in treatment of
      metastatic lung cancer, effective method is lacked. This study was designed to
      investigate the treatment of spontaneous metastatic lung cancer by interleukin-12
      (IL-12) gene-modified dendritic cells (DC) vaccine. METHODS: The spontaneous
      metastatic lung cancer model, prepared by injection of the 3LL Lewis lung cancer
      cells into the footpads of C57BL/6 mice, were treated by subcutaneous vaccination
      with tumor antigen peptide Mut1-pulsed, IL-12 gene-modified dendritic cells (DC
      IL-12/Mut1) derived from the normal bone marrow. After treatment, the lung
      weight, the number of lung metastatic nodes, the survival time of the tumor
      bearing mice were observed, and the NK and CTL activities were respectively
      determined. RESULTS: Compared with mice treated with Mut1-pulsed, control LacZ
      gene modified DC and untreated DC, tumor-bearing mice treated with DC-IL-12/Mut1
      had the lightest lung weights (P < 0.01), the least lung metastatic node numbers
      (P < 0.01), the longest survival time (P < 0.01), also with the induction of
      potent CTL activity (P < 0.01) and NK activity (P < 0.01). CONCLUSION: Tumor
      antigen-pulsed, IL-12 gene-modified dendritic cells have significant therapeutic
      effects on the spontaneous metastatic lung cancer, the possible mechanism
      involved with induction of CTL activity and enhancement of NK activity.

PMID- 12520742
TI  - [Expression of lung resistant-related protein in ovarian cancer and its clinical
      significance].
AB  - BACKGROUND & OBJECTIVE: It was reported that there was negative correlation
      between the over-expression of lung resistant-related protein (LRP) and the
      sensitivity of cisplatin and cyclophosphamide. Also it was reported that the over
      expression of LRP could predict the chemosensitivity and prognosis of ovarian
      cancer, and it was an independent index of remission and exist period. This study
      was designed to investigate the function of LRP in cisplatin resistance and the
      relationship with prognosis of ovarian cancer by combining with the
      chemosensitivity test. METHOD: 1. ATP bioluminescence assay was used to determine
      the drug sensitivity of 50 specimens of fresh epithelial ovarian cancer tissues.
      Patients' responses were obtained by accepted clinical assessment methods after
      three treatment courses. 2. Expression of LRP in 50 paraffin specimens of ovarian
      cancer was determined using immunohistochemistry. RESULTS: 1. The non
      overexpression of LRP in ovarian cancer was 24%, and the overexpression of LRP
      was 76%. 2. The non-overexpression of LRP in the cisplatin-sensitive ovarian
      cancer was 10/12(75%), while in the cisplatin-resistance was 3/12(25%). There was
      no significantly different. 3. The over-expression of LRP was increased in
      advanced and low grade ovarian cancer, and there was significantly different.
      CONCLUSIONS: Expression of LRP is related to stages, grades, and chemosensitivity
      of ovarian cancer, and it could become an index of screening drug and judging the
      prognosis of patients.

PMID- 12520743
TI  - [Primary study on establishment of namalwa 12/MTX resistant cell strain and its
      mechanism].
AB  - BACKGROUND & OBJECTIVE: Methotrexate has been used to treat malignant tumor for
      50 years. Different mechanisms of methotrexate resistance has been known in
      various kinds of leukemias. Because of individualized chemotherapy according to
      different drug metabolism in different leukemia patients, the treatment became
      more reasonable and scientific and the treatment effect has been gradually
      improved. However, there was few report about its drug resistance mechanism in
      lymphoma. This study was designed to establish Burkitt's lymphoma methotrexate
      resistant cell strain--Namlwa 12/MTX and study its resistant mechanism. METHODS:
      Namlwa 12/MTX resistant cell strain was established by repeated impulsed exposure
      to methotrexate. The difference of the methotrexate effect on Namlwa 12/MTX and
      Namlwa cell strains were evaluated with MTT method. The level of dihydrofolate
      reductase (DHFR) mRNA expression was assayed with RT-PCR. The function of the
      reduced folate carrier (RFC) were tested with 3H-MTX labeling and counted with
      beta-liquid scintillation counter. The capacity to form the polyglutamate
      methotrexate (MTXPG) in these cell strains was assayed with 3H-MTX labeling and
      high pressure liquid chromatography (HPLC) separation. RESULTS: More than 20
      times methotrexate resistance was found in Namalwa 12/MTX cell strain in
      comparison with the Namalwa cell strain. This resistance was not associated with
      the dysfunction of the RFC, but was closely associated with the amount of MTXPG
      formed. The amount of total MTXPG (MTXPG1-6) formed in these 2 cell strains was
      (1583 +/- 26) pmol/10(9) tumor cells and (4453 +/- 236) pmol/10(9) tumor cells,
      respectively (P < 0.05), while the amount of long chain MTXPG (MTXPG4-6) formed
      only accounted for 5.5% and 25.4% of the MTXPG1-6, respectively (P < 0.05). The
      level of DHFR mRNA expression was gradually increased with the formation of the
      drug resistance in Namalwa 12/MTX. CONCLUSION: Synthesizing difficulty of MTXPG
      and over-expression of DHFR mRNA level result in methotrexate resistance in
      Namalwa 12/MTX cell strain.

PMID- 12520744
TI  - [Inhibition of mixture of lucid garoderma and lucid garoderma spore on tumor cell
      in vitro and in vivo].
AB  - BACKGROUND & OBJECTIVE: Garoderma lucidum (lingzhi) is a kind of medicinal fungus
      with a long history in China as a valuable tonic folk remedy. It has been
      demonstrated that lingzhi had growth inhibition effect against implanted mice
      tumors. It is generally regarded that anti-tumor action of lingzhi is induced by
      promoting function of immune system. Recently, we found that mixture of lucid
      garoderma and lucid garoderma spore (MLGLGS) could markedly inhibit activities of
      topoisomerase I and II, so this study was designed to further evaluate the
      inhibition effects of MLGLGS on tumor cell in vitro and in vivo. METHODS:
      Inhibition of MLGLGS on tumor cell were detected by MTT or SRB method in vitro
      study and by human tumor nude mice xenografts as models in vivo study. RESULTS:
      Among them, the IC50 values were lower than 2 mg/ml in P388, U-937, and HL-60
      leukemias, and lower than 4 mg/ml in 2 human lung cancer and 2 human gastric
      cancer cells, respectively. In vivo study revealed that MLGLGS had certain
      experimental therapeutic action on human lung tumor xenograft LAX-83 (dose: 1
      g/kg, inhibitory rate: 49.47%) and gastric xenograft SGC-7901 (dose: 2 g/kg,
      inhibitory rate: 43.09%). CONCLUSION: MLGLGS has inhibitory action on tumor cell
      at high concentration and high dosage.

PMID- 12520745
TI  - [Clinical results of 295 patients with Hodgkin's disease treated by chemotherapy
      predominant comprehensive modality].
AB  - BACKGROUND & OBJECTIVE: Hodgkin's disease (HD) is a chemo- and radio-sensitive
      hematologic malignancy. At present, improvement of cure rate, reduction of long
      term toxicity, and maintenance of good quality of life are the major issues in
      the treatment of HD. The results of long term follow-up from Cancer Center, Sun
      Yat-sen University were analyzed retrospectively in terms of efficacy and late
      side effects in this article. METHODS: The results of 295 patients with histology
      proven HD from 1970 to 2000, especially from 1980 to 2000 were analyzed.
      Meanwhile, multivariant analysis (COX model) was employed to determine the
      prognostic factor. RESULTS: A total of 295 HD patients were treated by
      chemotherapy-predominant comprehensive modality. The 5, 10, and 20 years overall
      survival for 295 HD patients were 63.5%, 55.8%, and 47.1%, respectively, with
      median survival time of 172.3 months (28-351.9 months) at the median follow-up
      time of 42.9 months (17-351.9 months). The 5, 10, and 20 years overall survival
      and disease-free survival were 79.6%, 74.5%, and 66.8% as well as 74.5%, 69.4%,
      and 69.4% respectively for the patients treated with regular chemotherapy and
      radiotherapy from 1980 to 2000. The incidence rate of late toxicities was low.
      Multivariate analysis demonstrated that age over 45-year-old, B symptoms and
      stage III/IV were the main prognostic factors (P = 0.000, P = 0.035, and P =
      0.047) in this clinical study. The prognosis of the patients with stage I/II and
      nodular sclerosis was better in comparison to stages III/IV and other histologic
      subtypes. CONCLUSIONS: Chemotherapy-predominant combined with involved fields
      irradiation play an important role in HD treatment with promising long term
      survival and lower late toxicities. Further investigation for this simplified and
      convenient comprehensive modality is warranted.

PMID- 12520746
TI  - [Phase III clinical study of a new anticancer drug atofluding].
AB  - BACKGROUND & OBJECTIVE: Atofloding (ATFU) is a new derivative of 5-fluorouracil.
      The phase I and II clinical study have been finished. The current study was a
      phase III clinical trail of ATFU. The aim of this study was to evaluate the
      efficacy, toxicity of ATFU combination chemotherapy and compare with ftorafur (FT
      207) in patients with gastric cancer, colorectal, esophageal cancer, and liver
      cancer. METHODS: A multicenter, open randomized controlled trial was carried out.
      A total of 320 patients with gastric cancer, colorectal, esophageal cancer and
      liver cancer were randomized into ATFU group (study group) and FT207 group
      (control group) (a ratio of 2:1), treated with MMC + VP-16 + ATFU (FT-207), DDP +
      HCPT + ATFU (FT-207), DDP + VDS + ATFU (FT-207), and ADM + MMC + ATFU (FT-207)
      regimen, respectively. The same dosage of combine drugs were used in the two
      groups. RESULTS: The response rates of the study group (213 cases) and the
      control group (107 cases) were 17.1% and 7.9% in gastric cancer (P > 0.05), 16.7%
      and 9.4% in colorectal cancer (P > 0.05), 20.0% and 24.6% in esophageal cancer (P
      > 0.05), 5.0% and 9.0% in liver cancer (P > 0.05), respectively. The major
      adverse effects were mylosuppression and gastrointestinal reactions which
      frequency and intensity had no statistical difference in the two groups.
      CONCLUSION: ATFU combination chemotherapy is effective and similar to FT207 in
      the efficiency and adverse effects for treatment of advanced GI cancers.

PMID- 12520747
TI  - [Phase II clinical trial of nedaplatin in advanced non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: The aim of this study was to observe the efficacy and the
      side effects of nedaplatin in treatment of non-small cell lung cancer (NSCLC).
      METHODS: This is a multi-center phase II clinical trial. The previously
      chemotherapy treated patients with NSCLC were administrated nedaplatin alone.
      Nedaplatin was given at 100 mg/m2, i.v., repeated every 3 weeks. The chemonaive
      patients with NSCLC were randomized to two groups. The combination trial group
      was given with nedaplatin + vindesine regimen, and the combination control group
      with cisplatin + vindesine. RESULTS: Of 138 patients, 16 were in the nedaplatin
      single drug group; 60 were in the combination trial group; and 62 were in the
      combination control group. All of the 16 cases in the single drug group, which
      were treated with platinum previously, achieved 12.5% of response rate. And the
      combination trial group and control group had a very similar response rate, which
      were 26.7% versus 25.8%, respectively. The incidence rates of neutropenia and
      anemia were similar in the two groups. But the incidence rate of thrombocytopenia
      was higher in the trial group than that in the control group. Nedaplatin has a
      possibility to result in mild nausea/vomiting. CONCLUSION: Nedaplatin is an
      effective platinum drug in the treatment of NSCLC, not only for no previously
      chemotherapy patients, but also for those patients resistant to
      cisplatin/carboplatin. Nedaplatin has a good clinical tolerance. And the main
      adverse reaction was myelosuppression, especially thrombocytopenia.

PMID- 12520748
TI  - [Comparison of effects of three chemotherapy regimens for advanced non-small cell
      lung cancer].
AB  - BACKGROUND & OBJECTIVE: The platinum-combination chemotherapy has been proved to
      be benefit to the patients with advanced non-small cell lung cancer (NSCLC), but
      the suitable regimen of chemotherapy has been much debated during the last
      decade. This study was designed to compare MIP regimen [mitomycin + ifosfamid +
      cisplatin], TP regimen [Taxol + cisplatin], and DP regimen [docetaxel +
      cisplatin] and to evaluate the efficacy of the three regimens in patients with
      advanced NSCLC. METHODS: Ninety-two patients were enrolled in this study, 32 for
      MIP, 30 for TP, and 30 for DP. The characteristics of patients were comparable
      except there were more stage IV patients and second chemotherapy patients in DP
      group. RESULTS: For MIP, TP, and DP groups, the objective response rates were
      43.8%, 40%, and 46.7%, respectively; the median duration of survival were 11, 10,
      and 12 months respectively; the 1 year survival rate were 46%, 40%, and 50%,
      respectively. The major toxicities were bone marrow suppression, nausea,
      vomiting, and alopecia. CONCLUSIONS: MIP, TP, and DP regimens are effective and
      safe chemotherapy protocols for the treatment of advanced NSCLC patients.

PMID- 12520749
TI  - [Comparison of NP and MVP regimen in treatment of advanced non-small cell lung
      cancer].
AB  - BACKGROUND & OBJECTIVE: Chemotherapy is the major treatment for advanced non
      small cell lung cancer (NSCLC). However, the efficacy is not satisfactory. From
      January 1996 to December 2000, two chemotherapy regimen [NP: vinorelbine(NVB) +
      cisplatin(DDP); MVP: mitomycin (MMC) + vindesine(VDS) + cisplatin] have been used
      to treat 110 advanced NSCLC patients. The response and major adverse reaction
      were analyzed and compared. METHODS: Forty-eight cases of advanced NSCLC (stage
      III-IV) patients were treated with NP (NVB: 25 mg/m2, d1, 8; DDP: 35 mg/m2, d1
      3). The other 62 cases were treated with MVP regimen (MMC: 6 mg/m2, d1; VDS: 3
      mg/m2, d1, 8; DDP: 30 mg/m2 d1-3). RESULTS: In NP group, the overall response
      rate was 50% (CR + PR = 24); medium response time was 5.5 months; medium survival
      time was 11 months. In MVP group, the overall response rate was 51.6% (CR + PR =
      32), medium response time and survival time were 6.5 and 14.5 months,
      respectively. The major toxicities were myelosuppression and phlebitis in NP
      group, nausea/vomiting, myelosuppression in MVP group, respectively. CONCLUSION:
      NP and MVP regimen for advanced NSCLC have similar response rate (P > 0.05). Deep
      vein injection and improved infusion can be used to prevent phlebitis in NP
      regimen.

PMID- 12520750
TI  - [Combination chemotherapy with Taxol and cisplatin for 57 patients with non-small
      cell lung cancer by intraartery and intravenous infusion].
AB  - BACKGROUND & OBJECTIVE: Although previous studies showed that intravenous
      infusion chemotherapy combined with Taxol and cisplatin (DDP) can improve the
      effects of the treatment of advanced non-small cell lung cancer (NSCLC), the
      results remained unsatisfactory because of the lower concentration of local
      chemotherapeutic agent. This study was designed to administrate the
      chemotherapeutic agents through the local artery and to evaluate the efficacy of
      the intraartery (IA) and the intravenous (i.v.) infusion chemotherapy combined
      Taxol with cisplatin (DDP) in the treatment of NSCLC. METHODS: Fifty-seven
      patients with advanced NSCLC were enrolled and randomized into two groups. Group
      A (27 patients) was given by IA chemotherapy consisting of Taxol 135 mg/m2 and
      DDP 80 mg/m2 within 3 hours in the first day. Group B (30 patients) was given by
      i.v. chemotherapy consisting of Taxol 135 mg/m2 and DDP 80 mg/m2 within 3 hours
      in the first day. The patients in two groups were repeatedly treated every 3-4
      weeks for at least 2 cycles. RESULTS: The recent effect was evaluated by the CT
      or X-ray results. Of the 57 patients, 1 case acquired complete response, 29
      partial response. The overall response rate was 52.63% with 66.67% (18/27) in
      group A and 40.00% (12/30) in group B. The median TTP was 5.5 months in group A
      and 4.0 months in group B. The median survival time was 13.5 months in group A
      and 10.5 months in group B. The 0.5, 1, 2, and 3-year survival rates were 85.18%,
      66.67%, 48.15%, and 18.51% months in group A, respectively. The 0.5, 1, 2, and 3
      year survival rates were 70.00%, 53.33%, 30.00%, and 6.67% months in group B,
      respectively. The main side effects were myelosuppression, gastrointestinal
      reactions and peripheral neuropathy. They could be effectively treated with large
      amount of vitamines, antacid, guastil, white blood cell stimulating drugs and
      liquid compensation. CONCLUSION: The artery infusion Taxol and DDP chemotherapy
      is one of the useful methods in the treatment of NSCLC patients. The local
      response rate in the patients treated by IA may be higher than those treated by
      i.v.

PMID- 12520751
TI  - [Teniposide and cisplatin compared with etoposide and cisplatin for treatment of
      small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: EP regimen[etoposide (VP-16) + cisplatin (DDP)] is a
      standard regimen for treatment of small cell lung cancer (SCLC), but the cure
      rate is still low. Teniposide (VM-26) is highly active single agent for SCLC as
      VP-16, and penetratable through blood-brain barrier. This clinical trial was
      designed to compare the efficacy and toxicity of teniposide plus cisplatin (VM-26
      + DDP) regimen and EP regimen in treatment of SCLC, and the possible role of VM
      26 on prevention of brain metastasis of SCLC. METHODS: A total of 70 previously
      untreated SCLC patients without brain metastasis were included; 34 patients
      received VM-26 + DDP and 36 patients received EP. The characteristics of patients
      were comparable according to chi 2 test. RESULTS: The overall response rate-was
      76.5% for VM-26 + DDP group with 12 complete response (CR) and 14 partial
      response (PR), and 69.4% in the EP group with 12 CR and 13 PR (P = 0.595). The
      median duration of survival was 10.4 months for VM-26 + DDP group versus 9.8
      months for EP group (P > 0.05). The 1, 2, and 5-year survival rates were 35.3%,
      14.7%, 8.8% in the VM-26 + DDP group; and 38.9%, 13.9%, 8.3% in the EP group (P >
      0.05, without statistical difference). The rate of brain metastasis was 5.9% for
      VM-26 + DDP group and 19.4% for EP group (P = 0.027, with statistical
      difference). The main toxicity was mylosuppression (I-II); there was no
      significant difference between the two groups (P > 0.05). CONCLUSION: VM-26 + DDP
      is a highly active regimen for treatment of SCLC; there is no difference in the
      effectiveness and toxicity versus EP regimen; VM-26 is possibly effective in
      prevention of brain metastasis in SCLC patients.

PMID- 12520752
TI  - [Role of induction chemotherapy with bleomycin A5 in treating stage T2 tongue
      squamous cell carcinoma].
AB  - BACKGROUND & OBJECTIVE: Induction chemotherapy play an important role in
      treatment of the patients with tongue squamous cell carcinoma. This study was
      designed to evaluate the role of induction chemotherapy with single agent
      bleomycin A5 in treating stage T2 tongue squamous cell carcinoma. METHODS: The
      authors retrospectively analyzed the influence of surgery and induction
      chemotherapy with single agent bleomycin A5 plus surgery on survival rate and
      locoregional control among 72 patients with tongue squamous cell carcinoma.
      RESULTS: The 5-year survival rates were 81.46% and 57.14% respectively for the
      group of surgery alone and the group of induction chemotherapy plus surgery, the
      difference between the two groups were significant (P = 0.0229). The rates of
      locoregional recurrence were 22.2%, 33.3% and the medial time of recurrence was
      20, 24 months respectively in the two groups. For the patients in stage II and
      stage III plus stage IV, there was no difference between the two groups for the 5
      year survival rate (P = 0.0949; P = 0.0739). For the patients in stage III plus
      stage IV, the rates of locoregional recurrence were 12.5%, 35.7% and the medial
      time of recurrence was 12, 12.8 months, respectively, in the two groups.
      CONCLUSIONS: It has no significant role in treatment of the patients with stage
      T2 tongue squamous cell carcinoma for single agent bleomycin A5. Induction
      chemotherapy using single agent bleomycin A5 did not improve the 5-year survival
      rate for early or late primary lesions. The impact on the control rate of
      locoregional recurrence would be studied further for single agent bleomycin A5.

PMID- 12520753
TI  - [Practical control methods for the dose individualization of anticancer drugs].
AB  - Most anticancer drugs are characterized by a narrow therapeutic index, wide inter
      patient variability of pharmacokinetic parameters and high toxicity. The need for
      dose individualization of anticancer drugs is now well accepted. The strategies
      that can be employed for optimizing dosage regimen were reviewed. The aim of this
      paper was to provide an insight into the feasibility of these techniques in
      anticancer chemotherapy and their application at all stages of clinical trials
      and practice.

PMID- 12520754
TI  - [Research advances on effect of arsenic trioxide on tumor].
AB  - Arsenic compounds are natural substances that have been used medically for more
      than 2,400 years in China. Since 1990s, Chinese physicians have began to use
      arsenic trioxide in treating the patients with acute promyelocytic leukemia
      (APL), and the results showed that arsenic trioxide was effective on APL
      patients. Further study of arsenic trioxide demonstrated that arsenic trioxide
      was safe and effective not only on patients with leukemia, but also on patients
      with many other kinds of malignant cancers. Arsenic trioxide exerted its anti
      cancer effects mainly by inhibiting the cell growth and angiogenesis, inducing
      the cell partial cytodifferentiation and apoptosis, etc. In addition, this review
      looked forward to the prospect of application of gene chip, a newly developed and
      powerful technology in analysis of gene expression profile, in elucidation of the
      mechanism of arsenic trioxide on tumor.

PMID- 12520755
TI  - New insights and new issues in developmental neurotoxicology.
AB  - Here, I will review accumulating evidence that during the developmental period of
      synaptogenesis, also known as the brain growth spurt period, neurons are very
      sensitive to specific disturbances in their synaptic environment. During this
      period, abnormal increases in NMDA glutamate (Glu) receptor activity triggers
      excitotoxic neurodegeneration, and abnormal inhibition of neuronal activity (by
      blockade of NMDA Glu receptors or excessive activation of GABAA receptors)
      triggers neuronal suicide (apoptosis). Only a transient disturbance, lasting for
      a few hours, is sufficient to trigger either excitotoxic or apoptotic
      neurodegeneration during this developmental period. Ethanol, which has both NMDA
      antagonist and GABAmimetic properties, triggers widespread apoptotic
      neurodegeneration in the developing rat, mouse or guinea pig brain, and this
      provides a likely explanation for the reduced brain mass and lifelong
      neurobehavioral disturbances associated with the human fetal alcohol syndrome
      (FAS). The brain growth spurt occurs in different species at different times
      relative to birth. In rats and mice it is a postnatal event, but in humans it
      extends from the 6th month of gestation to several years after birth. Thus, there
      is a period in fetal and neonatal human development, lasting for several years,
      during which immature central nervous system (CNS) neurons are exquisitely
      sensitive to environmental agents (the specific number and variety of which
      remains to be established) that can trigger widespread neurodegeneration by
      inducing specific abnormal changes in the synaptic environment. Agents identified
      thus far include drugs that may be abused by pregnant mothers (ethanol,
      phencyclidine (PCP) (angel dust), ketamine (Special K), nitrous oxide (laughing
      gas), barbiturates, benzodiazepines) and many medicinals used in obstetric and
      pediatric medicine as sedatives, anti-convulsants or anesthetics (all general
      anesthetics are either NMDA antagonists or GABAmimetics). Many other chemicals in
      the human environment remain to be evaluated for their ability to cause
      developing CNS neurons to commit suicide, and this provides an exciting challenge
      for the field of developmental neurotoxicology.

PMID- 12520756
TI  - T1-weighted hyperintensity in basal ganglia at brain magnetic resonance imaging:
      are different pathologies sharing a common mechanism?
AB  - Basal ganglia bilateral symmetric hyperintensity in T1-weighted sequences at
      magnetic resonance imaging (MRI) is recognized to be due to the presence of
      manganese deposits. This abnormal finding has been reported in occupational
      exposures, liver cirrhosis and total parenteral nutrition with unbalanced
      solutions. However, the same imaging is often observed "by chance" in brain MRIs
      of patients not belonging to these groups. In order to better understand which
      are the clinical conditions coexisting with such findings, we decided to study
      systematically patients which showed this kind of imaging, focusing on their
      manganese and iron status, as it is known that these two metals have similar
      properties and that iron-deficiency can competitively increase manganese
      absorption. The 20 patients studied underwent clinical evaluation and the
      following laboratory tests: whole blood iron and manganese, hemoglobin, plasma
      iron, transferrin and ferritin. The neuroradiologic evaluation was integrated by
      pallidal index calculation, in order to provide a semi-quantitative esteem of the
      hyperintensity. The patients could be classified into four subgroups:
      Parkinsonism, anemia, cirrhosis, central nervous system tumors. In 18 out of 20
      cases, we found abnormalities in iron and/or manganese-related values.
      Particularly, iron-deficiency seems to be frequent among patients showing brain
      MRI abnormalities compatible with manganese deposits in basal ganglia. This
      observation suggests that iron-deficiency could be an important risk factor for
      manganese-induced neurotoxicity and should, therefore, be accurately considered
      and treated.

PMID- 12520757
TI  - Induction of GADD45 and GADD153 in neuroblastoma cells by dopamine-induced
      toxicity.
AB  - Dopamine (DA) metabolism and oxidation produce both reactive oxygen species (ROS)
      and reactive quinones. These chemical species are implicated in dopamine
      neurotoxicity and neurodegeneration. In the present studies, human neuroblastoma
      (SK-N-SH) cells were exposed to toxic concentrations of dopamine (333 microM) in
      order to investigate molecular pathways involved in dopamine toxicity. cDNA
      hybridization array (microarray) technology demonstrated that GADD45 and GADD153
      (growth arrest and DNA-damage inducible) gene expression was increased in
      dopamine-treated cells (333 microM for 18 h). Subsequent Northern and Western
      blot analysis confirmed these changes in GADD45 and GADD153 gene expression. The
      antioxidant, ascorbic acid, significantly reduced the increase in GADD45 gene
      expression but did not significantly reduce GADD153 gene expression. Currently,
      the precise function of the GADD gene products is not known. It is known,
      however, that these genes are upregulated in response to stress to allow cells
      time to repair macromolecular damage. In the present case, GADD gene expression
      (manifested as increased mRNA and protein levels) preceded dopamine-induced
      cytotoxicity. It appears that dopamine, through the formation of reactive oxygen
      species and quinones, may damage cellular macromolecules to the point of inducing
      GADD gene expression. Other genes that displayed changes, but that have not been
      subjected to post-hoc confirmation, include clusterin (increased), ubiquitin
      (increased), CD27 ligand (increased), CD27BP (increased), and rac-PK-beta
      (decreased).

PMID- 12520758
TI  - Inhibition of muscarinic receptor-induced proliferation of astroglial cells by
      ethanol: mechanisms and implications for the fetal alcohol syndrome.
AB  - In utero exposure to ethanol is deleterious to fetal brain development. Children
      born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the
      most significant of which are central nervous system (CNS) dysfunctions, such as
      microencephaly and mental retardation. An interaction of ethanol with glial
      cells, particularly astrocytes, has been suggested to contribute to the
      developmental neurotoxicity of this alcohol. At low concentrations (10-100 mM)
      ethanol inhibits the proliferation of astroglial cells in vitro, particularly
      when stimulated by acetycholine through muscarinic M3 receptors. Of the several
      signal transduction pathways activated by these receptors in astrocytes or
      astrocytoma cells, which are involved in mitogenic signaling, only some (e.g.
      protein kinase C (PKC) zeta, p70S6 kinase) appear to be targeted by ethanol at
      the same low concentrations which effectively inhibit proliferation. Inhibition
      of astroglial proliferation by ethanol may contribute to the microencephaly seen
      in FAS.

PMID- 12520759
TI  - Chronic ethanol produces increased taurine transport and efflux in cultured
      astrocytes.
AB  - Due to ethanol's low potency and low level of toxicity, high amounts of ethanol
      are consumed to achieve pharmacological effects. Blood levels of ethanol in
      chronic alcoholics may reach as high as 80-100 mM. We undertook a series of
      studies to determine if these high levels of ethanol stimulated osmoregulatory
      processes in cultured astrocytes. The uptake and efflux of taurine, the major
      osmoregulatory amino acid with potentially neuroprotective actions, was assessed.
      In addition, uptake and efflux of the excitatory amino acid aspartate was studied
      since astrocytes are vital in maintaining proper synaptic excitatory amino levels
      through uptake, metabolism, and efflux. Ethanol exposure for 96 h resulted in
      increased uptake of both 3H-taurine and 3H-D-asparate. There were no significant
      changes in transporter function at 24 h consistent with the delayed time course
      of transporter up-regulation seen during chronic hyperosmotic stress. Following
      EtOH withdrawal, efflux of preloaded 3H-taurine was significantly increased as
      compared to controls for up to 1 h. In contrast to the efflux profile seen during
      hypotonic induced swelling and regulatory volume decrease (RVD), no increased 3H
      D-asparate efflux was demonstrated. Cell volume measurements suggest that
      inhibition of the normal RVD response be involved in the increased taurine
      release.

PMID- 12520760
TI  - Relationship between lipophilicity of C6-10 hydrocarbon solvents and their ROS
      inducing potency in rat cerebellar granule cells.
AB  - We have studied the effects of aliphatic, alicyclic, and aromatic C6-10 solvents
      on the formation of reactive oxygen species (ROS) in rat cerebellar granule cell
      cultures. ROS formation was assessed by monitoring oxidation of 2',7'
      dichlorofluorescin (DCFH) to the fluorescent compound 2',7'-dichlorofluorescein
      (DCF). We found that aromatic solvents with C > 7, and aliphatic and alicyclic
      solvents with C > or = 7 induce ROS formation in rat cerebellar granule cells in
      vitro. The response increased with increasing solvent concentration. The potency
      of the compounds within each homologous group seemed to be correlated to their
      octanol water partition-coefficients. The aromatic solvents were generally less
      efficient in inducing ROS formation than the aliphatic and the alicyclic
      compounds.

PMID- 12520762
TI  - Color vision and occupational chemical exposures: I. An overview of tests and
      effects.
AB  - The paper presents a summary of the literature published until December 2000 on
      effects from some industrial chemical exposures on color perception, as well as
      short descriptions of the tests applied. Several different tests have been used
      to study acquired alterations of color vision. These changes are frequently found
      in the blue-yellow axis. Many of the tests were originally designed to detect
      congenital alterations in the red-green axis, and thus have relatively low
      sensitivity when studying chemically induced deficits in color perception. At
      present, the Lanthony D15-desaturated panel seems most suitable for application
      in industrial settings, since it is clearly the most sensitive and easily
      administered test. Color vision seems to be a physiological function very
      sensitive to several chemicals. The potency of industrial chemicals to induce
      color vision deficiencies has often been investigated during the last two
      decades. The chemicals most frequently studied are different solvents and
      mercury. Pronounced effects on color perception have been reported following
      chronic exposure to organic solvents such as styrene, carbon disulphide,
      perchloroethylene, n-hexane and solvent mixtures, and to organic as well as
      inorganic mercury. The effect of occupational toluene exposure seems not as well
      established, since only slight effects and several negative studies have been
      reported. For some of these compounds the effect on color vision has been further
      established through the finding of clear dose-effect relationships. In a few
      cases, even acute exposure situations, e.g. exposure to toluene for a few hours
      or acute alcohol intake, seem to affect color perception. Follow-up studies are
      needed to investigate the possible reversibility of effects in relation to
      discontinued or reduced exposures.

PMID- 12520761
TI  - EUROQUEST--a questionnaire for solvent related symptoms: factor structure, item
      analysis and predictive validity.
AB  - The study evaluates the factor structure and predictive validity of the symptom
      questionnaire EUROQUEST (EQ) that had been developed with the goal of simplifying
      the evaluation of health effects associated with long-term solvent exposure. The
      EQ was added to the normal evaluation procedures for 118 male patients with
      suspected solvent-induced toxic encephalopathy (TE) referred to seven Swedish
      clinics of occupational medicine during an 18-month period. EQ was also completed
      by 239 males from a random sample of 400 Swedish males aged 25-64 years selected
      from the general population and a sample of 559 occupationally active male spray
      painters aged 25-64 years. Factor and item analyses of EQ responses were
      performed. Ordinary least square regression analysis was used to evaluate
      sensitivity and correlation to evaluate the specificity of EQ and the separate
      components. Questions concerning memory and concentration symptoms alone showed
      better sensitivity than the other five EQ dimensions singly or combined for the
      entire EQ and for a subset of questions approximating Q16, a widely used organic
      solvent symptom screening questionnaire. However, the diagnosis of TE required
      information in addition to exposure and responses to EQ and Q16-like questions.
      The results indicate that the subset of EQ questions concerning memory and
      concentration might replace the more cumbersome EQ and less sensitive Q16 in
      screening for TE, although none of the screening instruments alone replaces
      current clinical diagnostic procedures.

PMID- 12520763
TI  - Color vision and occupational chemical exposures. II. Visual functions in non
      exposed subjects.
AB  - This paper presents data on visual functions (visual acuity, contrast
      sensitivity, and several tests of color vision), in a group of 199 non-exposed
      healthy subjects with an even distribution over the age range 18-65 years, and
      sex. Although subjects with obvious congenital color vision deficiencies were
      removed from the analyses (four males), females were superior to males on several
      of the color vision tests applied. Age influenced visual acuity and contrast
      sensitivity, while color discrimination was less affected. Correlations between
      functions of the right and the left eye in the individual subjects were rather
      low, ranging from 0.40 to 0.73. Correlations between visual acuity and contrast
      sensitivity on the one hand and color discrimination ability on the other hand
      were still lower (r < 0.20). These low correlations between functions in the two
      eyes support the need for testing each eye separately.

PMID- 12520764
TI  - Evidence of zinc protection against 2,5-hexanedione neurotoxicity: correlation of
      neurobehavioral testing with biomarkers of excretion.
AB  - Risk prevention of human exposure against n-hexane neurotoxicity is relevant
      towards the protective measures to be proposed in occupational toxicology.
      Metabolic studies have identified 2,5-hexanedione (2,5-HD) as the main neurotoxic
      metabolite of n-hexane, which reacts with amino groups of lysine in axonal
      neurofilaments forming 2,5-dimethylpyrrole adducts, which are responsible for n
      hexane neurotoxicity. In the present study, we have investigated the interaction
      of zinc with 2,5-HD, by correlating the decrease of pyrrole derivatives excretion
      with changes of neurobehavioral effects. Two subchronic experiments (11 and 8
      weeks of exposure) were performed in Wistar rats exposed to different doses of
      2,5-HD (200, 400 mg/kg per day) and to the mixture of 2,5-HD + zinc acetate (200
      + 300 mg/kg per day) and (400 + 500 mg/kg per day). The results obtained show a
      significant increase in the excretion of pyrroles in the groups exposed to 2,5-HD
      alone as compared to controls, and a significant decrease in the excretion of
      pyrrole derivatives in the groups of rats co-exposed to 2,5-HD + zinc acetate
      when compared to the rats exposed to 2,5-HD alone. These biochemical changes were
      immediately evident after the first day of exposure. Simultaneously,
      neurobehavioral testing (rearing and ambulation in open field) was performed
      weekly in the same groups of rats. The results demonstrated a significant
      decrease in neurobehavioral dysfunction in rats co-exposed to 2,5-HD and zinc
      acetate. At the end of the exposure period, pyrroles levels returned to control
      values progressively, and the recovery of the neurotoxic effects was gradually
      established depending on the dose of exposure. The results suggest that zinc is a
      potential chemo-protector against 2,5-HD neurotoxicity which was identified by
      neurobehavioral testing. Moreover, pyrrole derivatives are good predictive
      biochemical biomarkers of 2,5-HD exposure and could be used as a complementary
      tool to characterize its neurotoxic effects.

PMID- 12520765
TI  - The consequences of methylmercury exposure on interactive functions between
      astrocytes and neurons.
AB  - Methylmercury (MeHg) is a highly neurotoxic, environmentally ubiquitous chemical
      that exerts its toxic effects by largely unknown mechanisms. Maintenance of
      optimal intracellular concentrations of glutathione (GSH) is vital for cellular
      defenses against damage from free radicals. Since astrocytes play an essential
      role in providing GSH precursors to neurons, studies were directed at the effect
      of MeHg on cystine transport in both cell types. Astrocytes accumulated cystine
      via three independent transporters, referred to as system XAG-, system XC-, and
      gamma-glutamyltranspeptidase (GGT). In contrast, neurons accumulated cystine
      exclusively via system XC- and GGT. MeHg potently inhibited cystine uptake in
      astrocytes (but not in neurons), and this effect could be fully accounted for by
      inhibition of the system XAG- transporter. The transport of glutamate in
      astrocytes is also inhibited by reactive oxygen species (ROS). Accordingly,
      additional studies examined the ability of thiol reducing or oxidizing agents to
      inhibit the astrocytic transport of 3H-D-aspartate, a glutamate analog. The
      antioxidant catalase significantly attenuated MeHg-induced inhibition of
      astrocytic 3H-aspartate uptake. Combinedly, these studies suggest that inhibition
      of cystine uptake and decreased astrocytic GSH levels and efflux reduce the
      availability of precursors for GSH synthesis in neurons. In addition, MeHg
      induced generation of H2O2 plays a role in the inhibition of astrocytic glutamate
      transport. These effects likely increase neuronal vulnerability to MeHg-induced
      oxidative stress, and excess N-methyl D-aspartate (NMDA) receptor activation
      leading to neuronal demise.

PMID- 12520766
TI  - Neurotoxic effects of aluminium among foundry workers and Alzheimer's disease.
AB  - BACKGROUND: In a cross-sectional case-control study conducted in northern Italy,
      64 former aluminium dust-exposed workers were compared with 32 unexposed controls
      from other companies matched for age, professional training, economic status,
      educational and clinical features. The findings lead the authors to suggest a
      possible role of the inhalation of aluminium dust in pre-clinical mild cognitive
      disorder which might prelude Alzheimer's disease (AD) or AD-like neurological
      deterioration. METHODS: The investigation involved a standardised occupational
      and medical history with particular attention to exposure and symptoms,
      assessments of neurotoxic metals in serum: aluminium (Al-s), copper (Cu-s) and
      zinc (Zn-s), and in blood: manganese (Mn-b), lead (Pb-b) and iron (Fe-b).
      Cognitive functions were assessed by the Mini Mental State Examination (MMSE),
      the Clock Drawing Test (CDT) and auditory evoked Event-Related Potential (ERP
      P300). To detect early signs of mild cognitive impairment (MCI), the time
      required to solve the MMSE (MMSE-time) and CDT (CDT-time) was also measured.
      RESULTS: Significantly higher internal doses of Al-s and Fe-b were found in the
      ex-employees compared to the control group. The neuropsychological tests showed a
      significant difference in the latency of P300, MMSE score, MMSE-time, CDT score
      and CDT-time between the exposed and the control population. P300 latency was
      found to correlate positively with Al-s and MMSE-time. Al-s has significant
      effects on all tests: a negative relationship was observed between internal Al
      concentrations, MMSE score and CDT score; a positive relationship was found
      between internal Al concentrations, MMSE-time and CDT-time. All the potential
      confounders such as age, height, weight, blood pressure, schooling years,
      alcohol, coffee consumption and smoking habit were taken into account.
      CONCLUSIONS: These findings suggest a role of aluminium in early neurotoxic
      effects that can be detected at a pre-clinical stage by P300, MMSE, MMSE-time,
      CDT-time and CDT score, considering a 10 micrograms/l cut-off level of serum
      aluminium, in aluminium foundry workers with concomitant high blood levels of
      iron. The authors raise the question whether pre-clinical detection of aluminium
      neurotoxicity and consequent early treatment might help to prevent or retard the
      onset of AD or AD-like pathologies.

PMID- 12520767
TI  - Influence of age on aluminum-induced neurobehavioral effects and morphological
      changes in rat brain.
AB  - Aluminum (Al) is potentially toxic for mammals. In contrast to well documented Al
      neurotoxicity, neurobehavioral studies of Al in rodents have generally not
      produced robust or consistent results. In the present study, 16 young male (21
      days old) and 16 old male (18 months) rats were exposed to 0 (control group) and
      100 mg/kg/day of Al administered as Al nitrate nonahydrate in drinking water
      concurrently with citric acid (356 mg/kg/day) for a period of 100 days. At the
      end of the exposure period, rats were evaluated for motor activity in an open
      field apparatus and learning in a passive avoidance test. After behavioral
      testing, rats were sacrificed and brain samples were collected to determine Al
      concentrations and to study synapses in the left CA1 fields of hippocampal
      formation. While no significant effects of Al exposure between groups could be
      detected on behavior, the total number of synapses decreased with age and Al
      exposure. In turn, the percentage of perforated synapses significantly increased
      in old Al-loaded rats.

PMID- 12520768
TI  - Constitutive and TCDD-induced expression of Ah receptor-responsive genes in the
      pituitary.
AB  - The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related substances cause a
      wide variety of pathological alterations, with the most severe being progressive
      anorexia and body weight loss. These features suggest a possible involvement of
      the nervous system and endocrine organs, including the pituitary gland. TCDD
      related toxicity is considered mainly to be mediated by the aryl hydrocarbon
      receptor (AHR) protein, which binds TCDD, and heterodimerizes with its partner
      protein, the aryl hydrocarbon receptor nuclear translocator (ARNT), and binds to
      xenobiotica responsive elements (XREs) in the promoter regions of
      biotransformation genes as well as genes involved in growth, differentiation and
      cellular homeostasis. In the present study, we have investigated the expression
      of AHR responsive genes in the pituitary of untreated and TCDD treated
      129/SV/C57BL/6 mice in vivo and in pituitary cells in vitro. After TCDD or beta
      naphthoflavone (beta NF) treatment, the relative levels of cytochrome P4501A1
      (CYP1A1) mRNA and protein were dramatically increased in pituitary cells. The AHR
      repressor (AHRR) mRNA level was induced 7-13-fold by TCDD and beta NF.
      Furthermore, the expression of the adrenocorticotrophic hormone (ACTH) precursor,
      the proopiomelanocortin (POMC) gene, was investigated. A three-fold increase in
      POMC mRNA was observed in the pituitary of TCDD treated mice. POMC mRNA level was
      also increased in the pituitary cell line AtT-20 after TCDD treatment. The
      proteins encoded by POMC translational products, ACTH and beta-endorphin, were
      found with immunocytochemistry staining to be increased in AtT-20 cells after
      TCDD exposure. The presence of several XRE sequences in the promoter region and
      in the first intron of the human POMC gene suggest that the up-regulation of POMC
      expression in the pituitary may play a role in the endocrine alterations induced
      by TCDD. All together, the results point to the pituitary gland being a direct
      target for TCDD.

PMID- 12520769
TI  - Chlorpyrifos shares stimulus properties with pentylenetetrazol as evaluated by an
      operant drug discrimination task.
AB  - Based on previous data from elevated plus-maze tests suggesting a possible
      anxiogenic effect of the insecticide chlorpyrifos (CPF), the experiment reported
      here was designed to determine whether this organophosphate (OP) caused an
      interoceptive discriminative stimulus (IDS) in rats similar to that produced by
      the anxiogenic drug pentylenetetrazol (PTZ). Rats were trained to discriminate
      PTZ (20 mg/kg) from saline, using a drug discrimination procedure. When
      appropriate lever selection was achieved, generalization tests were performed.
      Tests of various doses of PTZ showed that the drug exerts dose-dependent
      discriminative control over response. Two more generalization tests were
      conducted with 250 mg/kg of CPF and 76.8 mg/kg of LiCl for up to 9 days. Results
      revealed that CPF (250 mg/kg s.c.) produced a PTZ-like IDS that fully substituted
      for PTZ 24 h after injection and that subjective effects remain for at least 6
      days. However, administration of LiCl did not produce any generalization to PTZ
      on any of the days tested. These results suggest that CPF shares a site of
      action, and perhaps functional properties, with PTZ that last for several days,
      are not due to general malaise and should be taken into account in the use of
      cholinesterase inhibitors in the treatment of different types of dementia.

PMID- 12520770
TI  - [Characteristics of psychological features in patients with spinal pains,
      cerebrovascular pathology and fibromyalgia].
AB  - Three hundred thirty-seven patients with neurological symptoms of lumbar
      osteochondritis (163 patients, mean age 40.3 +/- 0.51 years), fibromyalgia (32
      patients, mean age 45.3 +/- 1.15 years), initial forms of cerebrovascular
      pathology (142 patients, mean age 46.8 +/- 0.56 years) and 40 healthy controls
      (mean age 43.2 +/- 1.07 years) have been examined using cliniconeurological and
      psychological diagnostic methods. Higher frequency of emotional tension was found
      in patients of all the groups (53.4, 65.6 and 61.3% respectively). Similar
      personality characteristics predominated both in patients with chronic back pain
      and in those with cerebrovascular pathology. Along with reaction to disease,
      other factors (chronic psycho-traumatizing influences, interpersonal conflicts of
      needs and personal reactivity deficit) promoted psychic dysadaptation.

PMID- 12520771
TI  - [Late-onset dysthymic states].
AB  - Sixty patients with dysthymic states which had emerged in later age of 60-80
      years were examined. Two clinical types of dysthymic states were described:
      anergic (20 patients) and hypothymic (40 patients). Different comorbid mental
      disorders--obsessive-phobic (14 cases), somatoform (10), personality deviations
      (20) and psycho-organic (7)--were found to be characteristic of late-onset
      dysthymic states. According to developmental features, late dysthymia was primary
      (first manifested in the elderly) and secondary (develops after several
      depressive episodes). In diagnostic terms, the former is considered as
      "dysthymia" (F34.1 ICD-10) and the latter--as "recurrent depressive disorder"
      (F33).

PMID- 12520772
TI  - [Radiation of parotid glands for salivary flow reduction in amyotrophic lateral
      sclerosis].
AB  - Radiation of the parotid and submandibular glands was performed in 18 patients
      with pronounced hypersalivation at a late stage of amyotrophic lateral sclerosis
      (ALS). Single bilateral radiation of the parotid and posterior submandibular
      glands was made in the dosage of 7.0-7.5 Gy. Salivation volume was measured
      before and after the radiation therapy. Sixteen patients exhibited satisfactory
      and marked salivary flow reduction during 4-6 months. Xerostomia developed in 1
      patient who needed assignment of artificial salivary substitute and 1 patient did
      not respond to the therapy. The patient's caregivers reported a positive effect
      in all the cases. Tolerance of the therapy was good except rare side effects.
      Radiation of the parotid glands significantly reduced salivary flow in ALS,
      especially in patients receiving an adequate amount of water.

PMID- 12520773
TI  - [Application of impulse complex modulated electromagnetic fields in management of
      patients with diabetic polyneuropathy].
AB  - One hundred and twenty-one patients with diabetic polyneuropathy (DP) underwent a
      clinical and electroneuromyographic investigation before and after treatment with
      impulse complex modulated electromagnetic fields (ICM EMF) of varying frequency
      (100 and 10 Hz). Based on TSS and NIS LL scale tests, a correlation between the
      progression and occurrence of the basic subjective and objective signs of the
      disease and a DP stage was revealed. The alterations of segmental and peripheral
      neuromotor system manifesting in reduction of muscular bioelectrical activity,
      impulse conduction velocities in efferent fibers of peripheral nerves and maximal
      M-response amplitude were found to be related to DP stage and diabetes mellitus
      duration. A decrease of H-reflex amplitude and Hmax/Mmax ratio measured in crural
      muscles proved to be the earliest and most significant electroneuromyographic DP
      trait. ICM EMF application promotes a regression of DP basic clinical symptoms,
      an improvement of conduction function of peripheral nerves and 1a afferents state
      as well as a reflex excitability of functionally different spinal motoneurons.
      Therapeutic efficacy of a 10 Hz ICM EMF, particularly for DP primary stages and
      diabetes mellitus up to 10-year duration, was proved.

PMID- 12520774
TI  - [Lymphocyte reaction and humoral immune response to brain specific protein in
      children with pathology of the central nervous system].
AB  - Blood lymphocyte reaction to brain specific protein (BSP) in vitro and anti-brain
      antibodies (AB) levels were studied in newborns and infants with perinatal
      central nervous system (CNS) damages of various severity. A relationship between
      severity of CNS damages and a lymphocyte reaction to BSP as well as immuno
      regulative index (IRI) changes. A combination of high AB to BSP levels with IRI
      elevation after cells incubation with BSP was found to be a favorable prognostic
      sign. In contrast, IRI reduction combined with higher AB levels appeared to be an
      unfavorable one.

PMID- 12520775
TI  - [Disturbance of the premorbid knowledge reproduction in patients with hemispheric
      and intraventricular brain damages].
AB  - One hundred four patients with hemispheric arteriovenous malformations (AVM)
      (frontal, parietal and temporal brain lobes), 21 patients with craniopharyngiomas
      and 21 patients with aresorptive hydrocephalus were studied. Disturbance of the
      premorbid knowledge reproduction was found in 12 patients with hemispheric AVM.
      All the patients survived severe intraventricular hemorrhage. Similar memory
      defects were detected in 3 patients with craniopharyngiomas and in 12 patients
      with hydrocephalus. In these cases medio-basal (periventricular) brain regions
      (frontal and temporal), preferentially of right hemisphere, and diencephalic
      region were damaged. Selective retrograde amnesia in all above damages was
      characterized by inability to recall dates, less often autobiography and events
      content. The author stressed a role of the processes of events sequence
      representation and of traces selectivity in "old" knowledge actualization in the
      mechanisms of studied disturbances development. A possible role of right and left
      hemispheres as well as diencephalic region in information coding and decoding is
      discussed.

PMID- 12520777
TI  - [Combination of frontal temporal dementia and motor neuron disorder].

PMID- 12520776
TI  - [Neuromorphologic and psychological correlates of electrical brain activity in
      patients with schizophrenia and their relatives].
AB  - The study aimed at elucidation of potential correlations between EEG features,
      neuromorphologic and psychological characteristics in patients with schizophrenia
      and in subjects with familial predisposition to the disease. EEG has been
      conducted in 71 patients, 162 first-degree relatives of schizophrenia subjects
      and 67 healthy controls. In the patients and relatives, correlations of power
      indices for 7 frequency ranges of resting EEG with computed tomography and
      cognitive parameters were analyzed. The patients revealed negative correlations
      between slow EEG rhythms and sizes of bodies as well as of posterior horns of
      lateral ventricules. Positive correlations were shown between expression of alpha
      and beta-bands and verbal memory. In the relatives, an increase of slow and fast
      EEG rhythms power correlated with reduction of sizes of ventricular system
      regions studied and with deterioration of cognitive indices (mental activity,
      attention, memory). Overall, the data obtained indicate negative functional
      consequences of slow and fast EEG rhythms power augmenting in subjects at high
      genetic risk for schizophrenia, but do not confirm a hypothesis that ventricular
      enlargement causes EEG slowing in schizophrenia.

PMID- 12520778
TI  - [Use of cluster analysis of rheoencephalogram for evaluation of dyscirculatory
      encephalopathy stages].

PMID- 12520780
TI  - [Mental state of patients in late period after surgery of prostate gland benign
      hyperplasia].

PMID- 12520779
TI  - [Dynamics of asthenic syndrome in patients with major head arteries pathology at
      preclinical stage].

PMID- 12520781
TI  - [Treatment of mental autonomic disorders with Notta drugs].

PMID- 12520782
TI  - [Use of dopamine analogs in Parkinson's disease treatment].

PMID- 12520783
TI  - [Posttraumatic stress disorder in children and adolescents].

PMID- 12520784
TI  - [Value of magnesium in the pathogenesis of nervous system disease].

PMID- 12520785
TI  - Health and human rights. A South African experience.

PMID- 12520786
TI  - Ideas on how to retain family physicians.

PMID- 12520787
TI  - Larger cuffs accommodate bigger arms.

PMID- 12520788
TI  - Sojourn in South Africa.

PMID- 12520789
TI  - Mental health care and nutrition. Integrating specialist services into primary
      care.
AB  - PROBLEM BEING ADDRESSED: Primary care reform is an important component of health
      services restructuring. One of the goals of primary care reform is to integrate
      specialized services into primary care settings. To date, few programs have
      successfully achieved this. OBJECTIVE OF PROGRAM: To integrate specialized mental
      health services into the offices of family physicians through the Hamilton Health
      Services Organization (HSO) Mental Health and Nutrition Program. MAIN COMPONENTS
      OF PROGRAM: Since 1994, the Hamilton HSO Mental Health and Nutrition Program has
      integrated mental health counselors, psychiatrists, and dietitians into the
      offices of 87 family physicians. Activities of specialists are coordinated by a
      central administrative body. CONCLUSION: Lessons learned from this program can
      indicate how to succeed in integrating specialist services into primary care
      offices.

PMID- 12520790
TI  - Case report: allergic contact dermatitis and new-onset asthma. Chromium exposure
      during leather tanning.

PMID- 12520792
TI  - Caught in the middle: ethics and human rights.

PMID- 12520791
TI  - Return to work after occupational injury. Family physicians' perspectives on soft
      tissue injuries.
AB  - OBJECTIVE: To document physicians' views about facilitating factors for and
      barriers to their helping workers recover after occupational soft-tissue injuries
      and to ascertain physicians' knowledge and attitudinal barriers to their
      involvement in return to work. DESIGN: Faxed survey. SETTING: Manitoba family
      practices and emergency departments. PARTICIPANTS: General practitioners, family
      physicians, and emergency physicians regularly caring for injured workers. MAIN
      OUTCOME MEASURES: Physicians' ranking of facilitating factors and barriers,
      changes to help their involvement in return to work, and their attitudes and
      knowledge about return to work. RESULTS: Respondents and nonrespondents were
      demographically similar, 232 physicians (51.3%) responded. Respondents believed
      the main facilitating factors were physicians' ability to explain the nature and
      prognosis of injuries to workers (69%) and the willingness of workplaces to
      accommodate injured workers (26%). The main barriers were workers'
      misunderstandings and fears about their injuries (70.7%) and non-supportive
      supervisors and co-workers (20.8%). The most frequently requested change was
      better workplace job accommodation (48%). Most physicians agreed they had a role
      in planning return to work and were aware of the effect of job satisfaction,
      psychosocial elements, and work-related factors. Despite supporting evidence,
      only one third of physicians stated they would say "try to continue usual
      activities" to patients with occupational low back pain. CONCLUSION: Most
      physicians seemed aware of their role in return to work and the effect of
      occupational factors, but their advice on activity after injury differed from
      that in practice guidelines.

PMID- 12520793
TI  - Faces scale copyright.

PMID- 12520794
TI  - Childhood obesity: a public health threat.

PMID- 12520795
TI  - A model for improving communication in children's services.

PMID- 12520796
TI  - Consumer evaluation of a head injury assessment and rehabilitation unit.
AB  - This study was undertaken to assess parents' evaluations of the services provided
      by a children's head injury rehabilitation unit. A questionnaire was designed to
      determine levels of satisfaction with seven aspects of care: physical
      surroundings, transfer of information, convenience and accessibility, discharge
      procedure, perceived technical competence, staff's interpersonal skills and
      general satisfaction. A sample of 16 sets of parents of former patients was
      identified and sent a copy of the questionnaire. Fourteen questionnaires were
      returned (response rate of 87.5 per cent). Results showed that overall levels of
      satisfaction were high, with respondents' ratings ranging from 3.23 to 4.38 (on a
      scale of one to five). Satisfaction with convenience/accessibility and discharge
      procedure was rated significantly lower than the other five sub-scales. The study
      focused attention on areas where improvements were needed and supported the
      unit's goal of providing a consumer-led service.

PMID- 12520797
TI  - Time to go home: assisting families to take their child home following a planned
      hospital or hospice death.
AB  - During the past decade an increasing number of children whose deaths are planned,
      have died in their own homes. Smaller numbers die in hospitals and children's
      hospices. A minority of parents has always taken their child home with them after
      death from hospital or hospice. A survey was carried out to identify the numbers
      of children who are taken home in this way from selected hospitals and children's
      hospices in Southern England and South Wales. Information was sought on current
      policies and practices and the views of professionals. Replies from 20 units
      suggest that fewer than 10 per cent of children are taken home. Seven of the
      units had written policies and these generally had a higher rate of taking home.
      All hospitals/hospices should have a bereavement policy sensitive to the unique
      needs of children and families and including guidance on taking the child home
      should they wish to.

PMID- 12520798
TI  - Learning from experience: a first-year student reflects.

PMID- 12520799
TI  - Inter-professional collaboration and children with asthma.

PMID- 12520800
TI  - Work-based learning in pre-registration programmes.

PMID- 12520801
TI  - Paediatric pharmacological principles: an update. Part 3. Pharmacokinetics:
      metabolism and excretion.

PMID- 12520802
TI  - NMC ponders controversial indemnity insurance question.

PMID- 12520803
TI  - Warning issued about morning sickness remedy.

PMID- 12520804
TI  - Pregnant asylum seekers in detention.

PMID- 12520806
TI  - Passive smoking initiative.

PMID- 12520805
TI  - Healthy start.

PMID- 12520807
TI  - BMA calls for ban on smoking in public places.

PMID- 12520808
TI  - Listening to mothers.

PMID- 12520810
TI  - The pregnant pagan.

PMID- 12520809
TI  - Labour and spirituality.

PMID- 12520811
TI  - Antenatal classes and spirituality. An oxymoron or opportunity for transcendancy?

PMID- 12520812
TI  - The placenta. Symbolic organ or waste product?

PMID- 12520813
TI  - The rhombus of Michaelis. A key to normal birth, or the poor cousin of the RCT?
      Interview by Sara Wickham.

PMID- 12520814
TI  - Thrush and breastfeeding.

PMID- 12520815
TI  - Midwifery basics. Antenatal care--blood tests in pregnancy.
AB  - Joanna is now 16 weeks pregnant. She has been feeling particularly tired and her
      mum suggested that she might be anaemic. Louis is rather insulted as he prides
      himself on buying the best fresh ingredients from the local market, they love
      cooking and eat plenty of fruit and vegetables. Joanna had a full blood count
      taken by the community midwife who came to the flat to do her booking history.
      The midwife said that the surgery would contact her if she needed treatment for
      anaemia, but she hasn't heard anything yet.

PMID- 12520816
TI  - Northern Ireland: the way forward.

PMID- 12520817
TI  - Policy documents which impact on midwives. The Scottish dimension.

PMID- 12520818
TI  - Consent and the code.

PMID- 12520819
TI  - New aspects of the blood coagulation cascade, anticoagulants and vein thrombosis
      in Asia.
AB  - PURPOSE: This review describes recent views on blood coagulation and
      abnormalities of its physiological control that predispose to thrombosis,
      suggests that venous thrombosis and pulmonary embolism are more prevalent in Asia
      than was previously thought, and examines recent trials of novel anticoagulants
      for thrombosis prevention. SOURCES: 'Medline' was used to search for publications
      in English or with English language abstracts. CONTENT AND CONCLUSIONS: The study
      of blood coagulation is basic to understanding clotting and bleeding disorders,
      their prevention and treatment. Tissue factor, factor Xa, and thrombin are
      pivotal; together with physiological controls (positive and negative feedback
      loops, and natural anticoagulants) that first enhance thrombin generation but
      then preserve vessel patency by limiting haemostatic plug formation to areas of
      injury. Abnormalities in these mechanisms can increase thrombosis risk
      (thrombophilia). The traditional impression that venous thromboembolism is rare
      in Asia has been reinforced by the rarity of thrombophilic genetic polymorphisms
      outside of European populations. Nevertheless, there is increasing evidence for
      an increasing prevalence of symptomatic vein thrombosis and pulmonary embolism in
      Asia, and that thrombosis rates in 'high risk' clinical settings among elderly
      patients (as after major joint surgery or a stroke) now approach levels reported
      from the West. This indicates the need for greater clinical awareness of these
      conditions. Drugs now used routinely for thrombosis prevention in the West
      (especially low molecular weight heparins) are effective and relatively safe. New
      anticoagulants were even more effective in recent trials. There is urgent need
      for studies in Asia that define the locally relevant benefits and hazards of the
      increasing range of agents now available.

PMID- 12520820
TI  - Recent advances in the obstructive sleep apnoea/hypopnoea syndrome.

PMID- 12520821
TI  - Immunotherapy in autoimmune diseases.
AB  - Immunotherapy has the potential to modify or re-balance the immune system and
      hence useful in the management of autoimmune conditions. This article aims to
      review clinically useful immunotherapies available for treatment of autoimmune
      conditions, with particular emphasis on Type I diabetes mellitus, multiple
      sclerosis, rheumatoid arthritis and systemic lupus erythematosus. A Medline
      search for the period 1992 to 2002 (10 years) using the unrestricted keywords
      "immunotherapy AND autoimmune" was done. Full-length articles were selected for
      reviews based on the contents of their published abstracts. Additional Medline
      searches were focussed on the keywords "immunotherapy AND diabetes mellitus",
      "immunotherapy AND multiple sclerosis", "immunotherapy AND rheumatoid arthritis",
      and "immunotherapy AND systemic lupus erythematosus". Relevant publications
      referenced in the reviewed literature were further included for review, if not
      present in the original Medline search. Immunotherapy in Type I diabetes mellitus
      has focussed on the induction of tolerance to beta cell antigens, and in multiple
      sclerosis trials of anti-alpha 4 integrins and altered peptide ligand of myelin
      basic protein (MBP 83-99) showed initial promising results. The use of anti
      cytokine therapy (anti-TNF alpha and IL-1Ra) in rheumatoid arthritis has improved
      the quality of life of patients with refractory disease. The use of anti-CD20
      monoclonal antibody for in vivo B cells depletion and early trials of autologous
      peripheral stem cell transplants represent additional immunomodulatory treatment
      modalities for systemic lupus erythematosus patients. Better understanding of
      autoimmune conditions and advances in the production of humanized monoclonal
      antibodies, promises better immunotherapy in the near future.

PMID- 12520822
TI  - Leveraging on information technology to enhance patient care: a doctor's
      perspective of implementation in a Singapore academic hospital.
AB  - Information technology (IT) can improve the safety of patient care by minimising
      prescribing errors and organising patient-specific information from diverse
      databases. Apart from legibility, prescribing safety is enhanced as online access
      to databases carrying patient drug history, scientific drug information and
      guideline reference, and patient-specific information is available to the
      physician. Such specific information includes discharge summaries, surgical
      procedure summaries, laboratory data and investigation reports. In addition,
      decision support and prompts can be built in to catch errant orders. For such
      system implementations to work, the IT backbone must be fast, reliable and simple
      to use. End-user involvement and ownership of all aspects of development are key
      to a usable system. However, the hospital leadership must also have the will to
      mandate and support these development efforts. With such support, the design and
      implementation team can then map out a strategy where the greatest impact is
      achieved in both safety and enhanced information flow. The system should not be
      considered a finished work, but a continual work in progress. The National
      University Hospital's continuously updated Computerised Patient Support System
      (CPSS) is an example of an IT system designed to manage information and
      facilitate prescribing. It is a client-server based, one-point ordering and
      information access portal for doctors that has widespread adoption for drug
      prescription at outpatient and discharge medication usage areas. This system has
      built in safety prompts and rudimentary decision support. It has also become the
      choice means of accessing patient-related databases that impact on diagnoses and
      management.

PMID- 12520823
TI  - The clinician meets the computer--uneasy bedfellows.
AB  - The transformation of healthcare has been one of the great, but unfulfilled,
      promises of the information technology revolution. This disappointment has been
      due in part to the enormously complex processes involved in bedside clinical
      care. Selective adoption of advances in information technology has resulted in
      enhancement of point-of-care healthcare delivery, medical record management and
      professional communication. However, the introduction of these refinements has
      encountered resistance, as well as sparked new challenges. The exciting progress
      in this field is reviewed, with reference to global and local developments.

PMID- 12520824
TI  - Update in the management of stroke.
AB  - Recent advances have improved the outlook for patients with stroke, Singapore's
      fourth leading cause of death. Stroke unit care reduces death, dependency and
      institutionalisation, independent of age, gender and stroke severity.
      Neuroimaging is essential prior to initiation of specific therapies. While
      computed tomography (CT) Head remains the most widely used modality, magnetic
      resonance imaging (MRI), particularly diffusion weighted imaging (DWI) has
      enhanced the positive diagnosis of ischaemic stroke. General medical measures
      include close monitoring, adequate oxygenation, avoidance of excessive blood
      pressure lowering, reduction of hyperthermia, control of hyperglycaemia, adequate
      nutrition, prevention of complications and early rehabilitation. Despite the risk
      of fatal intracranial haemorrhage, thrombolysis may improve outcomes in
      appropriately selected patients with ischaemic stroke. No safe and effective
      neuroprotectant has been found. While suboccipital craniectomy is established for
      large cerebellar infarcts and haemorrhage, surgical evacuation of supratentorial
      haemorrhage has not been shown to be beneficial. Hemicraniectomy reduces
      mortality after massive hemispheric ischemic stroke. Early and sustained
      antiplatelet use after atherothrombotic stroke reduces stroke recurrence. Stroke
      recurrence is also reduced by sustained warfarin use for cardioembolic stroke,
      carotid endarterectomy for severe symptomatic internal carotid artery stenosis,
      blood pressure lowering starting after the acute phase of stroke and lipid
      lowering. On-going clinical trails are likely to provide better treatments in the
      near future.

PMID- 12520825
TI  - Current therapeutic strategies for type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is now regarded a worldwide epidemic with diabetes
      related complications exacting a heavy toll on those with poor metabolic control.
      Although there is no cure currently, the therapeutic armamentarium has expanded
      over the last few years to five classes of oral agents--sulfonylureas,
      biguanides, meglitinides, thiazolidinediones and alpha-glucosidase inhibitors.
      Sulfonylureas continue to be the mainstay oral hypoglycaemic agents for type 2
      diabetics because they are potent insulin secretagogues and cost-effective.
      Metformin exerts its main effect by reducing hepatic glucose output and is proven
      to particularly benefit obese type 2 diabetics. Meglitinides are rapid-acting
      insulin secretagogues targeting a postprandial hyperglycaemia and this class of
      drug is useful for those who are at risk of hypoglycaemia with longer-acting
      sulfonylurea drugs. Thiazolidinediones constitute a new class of insulin
      sensitizers that work predominantly in improving glucose uptake by the adipose
      tissues and skeletal muscles. Alpha-glucosidase inhibitors delay the digestion
      and absorption of polysaccharides, thus attenuating postprandial hyperglycaemia.
      This review article briefly examines the nature of these oral agents, including
      the role of combination therapy and insulin where clinically indicated.

PMID- 12520826
TI  - High-dose therapy followed by autologous haematopoietic stem cell transplantation
      in multiple myeloma.
AB  - INTRODUCTION AND OBJECTIVES: The median survival of patients with multiple
      myeloma (MM) after conventional chemotherapy is 3 years or less. Previous studies
      have shown that high-dose therapy, supported by haematopoietic stem cell rescue,
      improves survival of patients with MM. We analysed the outcome of 29 myeloma
      patients who had autologous haematopoietic stem cell transplantation (AHSCT) in
      our institution over an 8-year period. MATERIALS AND METHODS: Between May 1993
      and August 2001, 29 patients with MM underwent high-dose therapy followed by
      unpurged AHSCT. There were 16 male and 13 female patients. The median age of the
      patients was 52 years (range, 31 to 67 years). All patients had at least a
      partial remission after initial chemotherapy. The preparative regimen for the
      AHSCT was melphalan 200 mg/m2 in 25 patients, melphalan-total body irradiation in
      1 patient, and busulphan-cyclophosphamide (BuCy) in 3 patients. Twenty-three
      patients received peripheral blood stem cells (PBSCs) autograft, 3 patients
      received bone marrow autograft and 3 patients received both. RESULTS: Treatment
      related death occurred in only 2 patients (7%). The median time to neutrophil
      engraftment was 11 days (range, 8 to 22 days). With a median follow-up period of
      18.5 months, the 5-year overall survival (OS) and event-free survival (EFS) rates
      were 71% and 21%, respectively. The OS was found to be superior to a group of
      historical controls who were treated with conventional chemotherapy without
      transplantation (71% vs 19%; P = 0.014). CONCLUSION: In conclusion, high-dose
      therapy followed by AHSCT is safe and beneficial for patients with MM.

PMID- 12520827
TI  - Early unplanned readmission of elderly in Singapore: a retrospective study.
AB  - STUDY OBJECTIVE: To study the incidence and profile of elderly patients requiring
      early unplanned readmission within 15 days of discharge from a regional hospital
      and the predictive factors for readmission. PATIENTS: All patients (n = 150) aged
      65 years old and above who were readmitted within 15 days into the hospital's
      geriatric unit in the western region of Singapore over a period of 10 months were
      retrospectively studied. METHODOLOGY: Demographic data, information on patients'
      medical problems and social environment were gathered from the patients' medical,
      nursing and therapist records. A control group (n = 103) consisting of patients
      not readmitted over 15 days were gathered over the same period. RESULTS: The
      percentage of readmission over the period between 1 January 1999 and 31 October
      1999 was (150/1632) 9.2% (95% CI, 7.8% to 10.7%). There were a total of 150
      patients with an equal number of male and female patients. The patients had a
      mean of 4 medical problems. Cardiovascular disease was noted in 73% (95% CI,
      65.5% to 80.2%) of the patients during the index admissions. They were noted to
      be ambulatory and were staying with their own families. Half of the patients were
      discharged from the index admission with no adjustment to their previous care
      system. The majority of patients (68.7%; 95% CI, 59.9% to 75.4%) required
      readmission because of medical problems. Fifty per cent of the patients admitted
      for a new medical complaint were secondary to sepsis. Thirty per cent (95% CI,
      22.8% to 38.0%) of the study population had both medical and social issues. The
      main predictive factors noted when compared to a control group of 103 patients
      (using a stepwise logistic regression model) were number of medical problems (P =
      0.0128; OR = 1.4; 95% CI, 1.1 to 1.9) and number of previous admissions (P =
      0.005; OR = 1.6; 95% CI, 1.2 to 2.3). CONCLUSION: Unplanned readmissions are
      relatively common in elderly patients. They cannot be entirely prevented in view
      of multiple chronic illnesses. Further studies, looking at early detection of
      medical problems and prevention of nosocomial infections are warranted to
      decrease the problem of readmissions for this group of elderly.

PMID- 12520828
TI  - Cancer incidence in Singapore, 1998 to 1999.
AB  - The age-standardised incidence rates for all cancers for 1998-1999 were 235.0 per
      100,000 in males and 199.8 per 100,000 in females. The corresponding rates for
      1993-1997 were 233.1 per 100,000 in males and 198.1 per 100,000 in females. The
      greatest difference was for breast cancer in females with age-standardised
      incidence rates increasing from 46.1 to 53.1 cases per 100,000 persons per year
      between these time periods. There also appears to be a shift of the peak age
      specific incidence for breast cancer from premenopausal to postmenopausal years
      over this period. This suggests that our breast cancer incidence pattern is
      rapidly becoming more similar to populations in the West.

PMID- 12520829
TI  - A retrospective study on the characteristics of androgenetic alopecia among Asian
      races in the National Skin Centre, a tertiary dermatological referral centre in
      Singapore.
AB  - OBJECTIVE: To study the characteristics and psychosocial impact of androgenetic
      alopecia among Asian races. METHODOLOGY: A retrospective telephone interview
      study of patients managed for androgenetic alopecia in 1997 in a tertiary
      dermatological referral centre in Singapore. RESULTS: Two hundred and fifty-six
      patients (111 females and 145 males) were included in the study. Their mean age
      at presentation was 33.7 years. There were no significant statistical mean age
      differences among the different races (Chinese, Malay and Indian). The mean
      duration of disease before consultation was 31.2 months; 33.2 months for males
      and 28.9 months for females (ns). Almost all patients (96.4%) were socially
      embarrassed and "unhappy" about their androgenetic alopecia. Most (90.5%) sought
      treatment for "cosmetic" reason. Slightly more males sought treatment for
      cosmetic reason than female (P = 0.01). 7.5% were worried about an underlying
      systemic disease as a cause of their alopecia. A positive family history of
      androgenetic alopecia was recorded in 58.9% (151/256). Male patients tend to have
      higher proportion of having a father or male sibling with similar problem,
      whereas female patients tend to have higher proportion of having a mother or
      females sibling with androgenetic alopecia. The predominant balding patterns for
      males were a combination of frontal, bi-temporal recession and vertex thinning
      (43%, 45% and 55%, respectively). Whereas in females, the predominant
      presentation was vertex thinning (60%) and, infrequently, frontal and bi-temporal
      thinning (19% and 15%, respectively). Diffuse pattern was also more predominant
      in females (28%) compared to males (10%). CONCLUSIONS: Most patients presented in
      their thirties with females presenting earlier than males and almost all patients
      presented for treatment for cosmetic reasons. Patients are generally unhappy
      about their appearance as a result of their alopecia. A strong positive family
      history appears to suggest that the disorder may be acquired through an autosomal
      dominant trait. Male patients tend to have a father or male sibling with similar
      condition and female patients tend to have a mother or female sibling with
      similar condition.

PMID- 12520830
TI  - Aseptic meningitis in children--the Singapore experience.
AB  - OBJECTIVE: To study the incidence, aetiology, clinical characteristics and
      management of paediatric aseptic meningitis in a paediatric hospital in
      Singapore. MATERIALS AND METHODS: Patients with cerebrospinal fluid (CSF)
      pleocytosis, a negative Gram stain and bacterial culture were reviewed
      retrospectively from 1 January to 31 December 2000. Eighty-seven patients who
      fulfilled the criteria for aseptic meningitis and without neurological deficits
      were studied. In addition, reverse transcriptase polymerase chain reaction (RT
      PCR) using pan enterovirus primers was subsequently performed on 73 of these CSF
      specimens which were available for storage. RESULTS: The incidence of aseptic
      meningitis was approximately 37 cases per 10,000 admissions. Non-polio
      enteroviruses were isolated from 29 of 64 (45.3%) CSF and 38 of 52 (73.1%) stool
      samples. RT-PCR was positive in 43 (58.9%) of the archived CSF specimens. The
      aetiologies of the remaining cases were mostly unidentified. Their ages ranged
      from 5 days to 12 years (median, 2 months). All patients except 1 had fever.
      Vomiting or poor feeding occurred in 44.7%, cough or running nose in 35.3%,
      irritability was observed in 35.3%, seizures in 7.1%, a rash in 10.6% and
      diarrhoea in 5.9%. All patients recovered without sequelae. The median CSF white
      cell count was 212 cells/mm3 (range, 7 to 12,000). The median glucose
      concentration was 2.7 mmol/L (range, 1.6 to 4.4). The median CSF/blood glucose
      ratio was 0.52 (range, 0.23 to 0.73). Median length of stay was 7 days (range, 4
      to 17). Eighty-four patients (96.6%) received antibiotics for a median of 5.5
      days (range, 2 to 14). CONCLUSION: Enteroviruses were the most common aetiologic
      agent identified. A method of early diagnosis using RT-PCR for enteroviruses is
      necessary to reduce the current duration of antibiotic usage and to decrease the
      length of hospital stay.

PMID- 12520831
TI  - Deep vein thrombosis is not rare in Asia--the Singapore General Hospital
      experience.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is perceived to be rare in Asia, but
      our recent clinical experience at Singapore General Hospital (SGH) suggests
      otherwise. Between 1996 and 1997, there were 388 cases of confirmed deep vein
      thrombosis (DVT). MATERIALS AND METHODS: All patients with symptomatic DVT
      confirmed by duplex ultrasound studies from January 1996 to December 1997 were
      retrospectively studied. Their case notes were searched for a record of
      predisposing risk factors. RESULTS: Ultrasound imaging indicated acute thrombosis
      in 320 patients (82.5%), and previous, but not acute thrombosis in 68 patients
      (17.5%). The overall frequency rate of acute DVTs was 15.8 per 10,000 hospital
      admissions. The average age of patients with acute thrombosis was 58.2 years.
      9.2% of patients developed pulmonary embolism (PE). Their most frequently
      recorded clinical predispositions were immobilisation (67%), malignancy (33%) and
      recent surgery (30%). One hundred and thirty patients were tested for
      antithrombin, protein C or protein S deficiency, and the presence of
      antiphospholipid antibody and 45 (35%) were found to have at least 1 positive
      result. CONCLUSION: DVT is not uncommon in Singapore. Our frequency rate of acute
      DVT of 15.8 per 10,000 admissions is much higher than previously reported rates
      of 2.8 and 7.9 per 10,000 admissions in 1990 and 1992, respectively. These
      findings confirm the need for increased awareness of VTE in Asian populations,
      and support the relevance of systematic studies of thrombosis risk and
      prophylaxis in Asia.

PMID- 12520832
TI  - CD4 lymphocyte enumeration in patients with human immunodeficiency virus
      infection using three-colour and four-colour dual-platform flow cytometry: an
      inter-laboratory comparative evaluation.
AB  - INTRODUCTION: This study aims to evaluate the correlation and agreement between 2
      methodologies of CD4 lymphocyte enumeration. MATERIALS AND METHODS: Fifty-two
      blood samples from patients with human immunodeficiency virus (HIV) infection
      were sent for CD4 lymphocyte enumeration at 2 major hospitals using dual-platform
      flow cytometry where the absolute lymphocyte counts were determined on separate
      haematology analyzers. CD4 cell enumeration was accomplished using 3-colour flow
      cytometry on the FACSCalibur cytometer (Becton Dickinson) in Hospital A and 4
      colour flow cytometry on the Coulter Epic XL cytometer (Beckman Coulter) in
      Hospital B. The percentages and absolute counts of CD4 lymphocytes obtained were
      analysed using both linear regression and Bland-Altman plots. RESULTS: On linear
      regression plots, the total white cell counts, absolute lymphocyte counts, CD4
      lymphocyte percentages and absolute CD4 counts from the 2 hospitals correlated
      well with correlation coefficients, r > 0.95. On the Bland-Altman plots, there
      was a mean difference of 0.13 x 10(9)/L and 0.06 x 10(9)/L in the total white
      cell and absolute lymphocyte counts from the 2 hospitals respectively. The CD4
      lymphocyte percentages revealed a mean difference of only 0.05% (95% limits of
      agreement, -3.6 to 3.7%) but there was a mean difference of 14/uL in the absolute
      CD4 lymphocyte counts (95% limits of agreement, -113 to 142/uL). CONCLUSIONS: The
      CD4 lymphocyte percentages obtained using the 3-colour and 4-colour flow
      cytometry correlated and agreed well. However, the absolute CD4 lymphocyte counts
      obtained using the dual-platform technique in both the hospitals did not agree
      well. Hence, absolute CD4 lymphocyte counts from the 2 hospitals cannot be used
      interchangeably in clinical practice due to poor inter-laboratory comparability.

PMID- 12520833
TI  - A preliminary study of the utility of combined cardiac markers in the evaluation
      of patients presenting early with suspected acute coronary syndrome.
AB  - OBJECTIVE: The aim of the study was to investigate and compare the usefulness and
      accuracy of various cardiac markers [troponin I, creatine kinase MB (CKMB) mass,
      creatine kinase (CK), CKMB activity] to aid early diagnosis of myocardial
      infarction. We also examined the ability of the various cardiac markers to
      prognosticate future adverse cardiac events. MATERIALS AND METHODS: Patients
      admitted within 8 hours of maximal chest pain suggestive of acute coronary
      syndrome with non-diagnostic electrocardiograms were recruited. Blood samples
      were obtained on admission to the wards and repeated 4 hours later. These results
      were later correlated to the final hospital discharge diagnosis. RESULTS: The 37
      patients in the study were a high-risk population with over 50% presenting with a
      Thrombolysis in Myocardial Infarction (TIMI) risk score of greater or equal to 3.
      Myoglobin was the most sensitive marker (100% sensitivity) in early prediction of
      patients who were subsequently diagnosed to have a myocardial infarction.
      Patients with an elevated troponin I level but normal CK and myoglobin levels had
      a significantly higher risk of developing a major adverse clinical event (MACE)
      within 3 months of the initial presentation. CONCLUSION: Myoglobin is the most
      sensitive marker when compared to CK, CKMB and troponin I for diagnosing patients
      presenting early with chest pain and a non-diagnostic electrocardiogram and who
      subsequently develop either a ST-elevation myocardial infarction or non-ST
      elevation myocardial infarction. Patients with an elevated troponin I level but
      normal CK and myoglobin levels are at higher risk of an adverse clinical event.

PMID- 12520834
TI  - Pilot study to assess the viability of a rape trauma syndrome questionnaire.
AB  - INTRODUCTION: Studies have revealed that rape victims undergo a number of
      psychological symptoms following the attack, which constitute a specific syndrome
      termed the rape trauma syndrome (RTS). Evidence of the RTS has been admitted as
      scientific testimony in the prosecution of sexual offences and has been integral
      in their successful conviction. The present study aims to assess the viability of
      a questionnaire designed to identify the RTS in victims of alleged rape.
      MATERIALS AND METHOD: A 77-item rape trauma syndrome questionnaire (RTSQ) was
      developed and administered to 30 women who reported rape and 57 nurses who formed
      the control group. The data were analysed using the Statistical Package for the
      Social Sciences (Windows Version 6.0). RESULTS: Statistical analysis suggested
      that the questionnaire was internally consistent and effective in uncovering
      significant differences between rape victims and controls in their experience of
      rape trauma symptoms. Rape victims scored significantly higher than controls on
      the RTS scale. Those who faked rape were also found to endorse a greater number
      of the rape trauma symptoms than actual rape victims, as well as a greater number
      of fictitious and unlikely symptoms. CONCLUSION: This pilot study confirmed the
      viability of the RTSQ and paves the way for a more rigorous examination of its
      reliability and validity. In the future, the questionnaire may be of use in
      ascertaining the veracity of victims' claims of rape in the conviction of sexual
      offences where circumstances are equivocal.

PMID- 12520835
TI  - Intravenous adrenaline or vasopressin in sudden cardiac arrest: a literature
      review.
AB  - INTRODUCTION: The chain of survival concept implies that provision of early
      access, early advanced care, including early intravenous drugs would improve
      survival in sudden cardiac arrest. Intravenous adrenaline (epinephrine) has been
      used as the drug of choice since 1906. What is the evidence for its
      effectiveness? Is vasopressin a better alternative? METHODS: We performed a
      systematic literature search in order to answer these questions. Evidence from
      the clinical trials that have been conducted on this subject was reviewed.
      RESULTS: Experimental evidence confirms the beneficial effect adrenaline has on
      coronary perfusion pressure. However, adrenaline has not been shown conclusively
      to improve survival in clinical trials. Extensive trials have also failed to show
      any benefit of high-dose adrenaline over standard doses. Vasopressin seems to be
      more effective than adrenaline in animal studies for treatment of cardiac arrest
      due to resistant ventricular fibrillation. However, it has yet to be proven to be
      superior to adrenaline in clinical trials. CONCLUSION: More research is needed
      into this area, especially randomised controlled trials studying the
      effectiveness of vasopressin. Meanwhile, in order to improve survival from sudden
      cardiac arrest, continuing effort should be made to achieve early initiation of
      cardiopulmonary resuscitation, early defibrillation and early advanced care.

PMID- 12520836
TI  - CerbB2 status in breast cancer: pathologic issues.
AB  - INTRODUCTION: CerbB2 status determination in breast cancer is currently performed
      for predictive and prognostic information. However, much has yet to be learned
      about the accuracy, reproducibility and clinical correlation of the different
      testing methods available today. This is a review of the testing methods commonly
      in use and their applications in the management of breast cancer. METHODS: A
      Medline search for review articles with keywords cerbB2, Her2 testing,
      immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and breast
      cancer was done. Manual cross-referencing from the afore-mentioned articles and
      perusal of the package inserts, recommendations and manuals from the
      manufacturers of various commercially available test kits were also performed.
      RESULTS: The 2 main methods of testing in use in most routine laboratories are
      IHC and FISH on formalin fixed, paraffin embedded, breast cancer tissue. There is
      no single, universally accepted method and the plethora of testing and
      interpretative protocols has confounded the issue of clinical correlation of
      cerbB2 status with outcome and patient selection for therapy. The current
      consensus in the literature is leaning towards FISH; however, as pointed out in
      this paper, the use of FISH as a routine test in most diagnostic laboratories is
      not yet a reality mainly due to cost, technical and manpower constraints. In this
      regard, IHC is by default the preferred choice in many routine laboratories.
      CONCLUSION: Universal standardisation of testing methods for cerbB2 status
      determination, together with further clinical studies on the correlation of each
      method with outcome and response to therapy, will aid in the identification of
      the ideal method for stratifying patients with breast cancer into prognostic and
      optimal therapeutic groups.

PMID- 12520837
TI  - Double omental hernia--case report on a very rare cause of intestinal
      obstruction.
AB  - INTRODUCTION: We report a case of transomental herniation of the ileum through a
      defect in the gastrocolic ligament with re-emergence through a defect in the
      gastrohepatic ligament. This type of herniation is extremely rare and a review of
      the literature is presented. CLINICAL PRESENTATION: A 41-year-old Chinese male
      presented with signs and symptoms of intestinal obstruction. TREATMENT: An urgent
      laparotomy was undertaken and he was found to have a rare form of intra-abdominal
      hernia. The hernia was reduced and the defects were closed. OUTCOME:
      Postoperative recovery was unremarkable. CONCLUSION: Urgent operation should not
      be delayed because of the high mortality associated with strangulation.

PMID- 12520838
TI  - Gemella empyema cured without antibiotics: a case report.
AB  - INTRODUCTION: Gemella are gram-positive bacteria that are commensals of the upper
      respiratory tract in humans and infrequently known to cause infections. CLINICAL
      PICTURE: We report a case of thoracic empyema due to Gemella morbillorum in an
      elderly Chinese male who had been having symptoms for 3 months and no response to
      multiple courses of antibiotics. INTERVENTION: The collection was drained with
      ultrasound guidance. OUTCOME: Drainage of the empyema produced rapid resolution
      of symptoms and no antibiotics were started. CONCLUSIONS: Gemella is a very rare
      cause of empyema which usually responds well to treatment.

PMID- 12520839
TI  - Sudden death due to granulomatous myocarditis: a case of sarcoidosis?
AB  - INTRODUCTION: We report a case of sudden death due to granulomatous myocarditis
      and propose that cardiac sarcoid could have been the underlying aetiology. This
      is the first case reported in Singapore. The differential diagnoses for
      granulomatous myocarditis including sarcoidosis and its cardiac manifestations as
      well as idiopathic giant cell myocarditis are discussed. CLINICAL PICTURE: A 53
      year-old Indian woman died suddenly and autopsy revealed bilateral hilar
      adenopathy and myocardial infiltrates which proved to be granulomatous in nature.
      CONCLUSION: Sarcoidosis may not be a rarity here and it is important to recognise
      the different clinical manifestations.

PMID- 12520840
TI  - Hospital ethics committees: will America's model work in Asia?
AB  - Hospital Ethics Committees (HECs), a well-established component of institutional
      healthcare in the United States (US), are beginning to take root in Asia. A major
      function of HECs is to provide ethics consultation in the clinical setting.
      Whereas the modus operandi for ethics consultation is reasonably uniform in the
      US, one should anticipate significant structural and functional deviations in
      Asia. For HECs to be effective in Asia, substantive and procedural modifications
      are necessary to accommodate fundamental cultural and attitudinal differences
      including differences within Asia itself.

PMID- 12520841
TI  - 12th chapter of surgeons lecture: shifting paradigms in the management of breast
      cancer--a surgical perspective.

PMID- 12520842
TI  - [Interdisciplinary complications conference--also a (simple) kind of quality
      assurance].
AB  - Documentation of complications is a "must" today. Several societies have been
      formed and several systems of documentation exist to fulfill these requirements.
      But there are also very simple tools for quality management in every hospital.
      Since 1995 all surgical/orthopedic interventions have been prospectively recorded
      at the hospital of Frutigen. Every other month a list of all operations and their
      complications is put together by the two surgeons-in-chief. This list is then
      presented at the so-called interdisciplinary complications-conference. This
      meeting is open to all employees of the hospital and to all medical doctors of
      the region. From the 1st January 1995 to the 31st December 2001 7396 surgical
      interventions were performed on in- or outpatients. 134 complications (1.8%)
      occurred. These were: 49/7396 infections (0.7%), 14/1395 re-osteosyntheses (1%),
      21/7396 hematomas requiring evacuation (0.3%), 8/7396 disturbances in wound
      healing (0.1%) and 42 other, postoperative complications. Postoperative infection
      occurred most frequently after appendectomies 10/251 (4%), the rate after
      internal fixation was 0.6% (9/1395). Hematomas were encountered most frequently
      after total joint replacement (hip and knee) 4/180 (2.2%), followed by inguinal
      hernias 4/287 (1.4%). The rate of re-osteosynthesis was highest after internal
      fixation of proximal humerus fractures 5/58 (8.6%). This systematic documentation
      of complications allows an analysis of the operative/perioperative management. By
      introducing specific measures (compression-bandage after operations of inguinal
      hernias and total hip prosthesis, new implant with rotational stability for
      proximal humerus fractures) an attempt can be made to reduce the rate of the most
      frequent complications. The public presentation of the complications at the
      meeting makes it possible to communicate good and bad results to the whole staff
      including the general practitioners, and the interdisciplinary mode of discussion
      permits the inclusion of not only the surgical but also all other possible
      aspects of the treatment of the patients.

PMID- 12520843
TI  - [Laparoscopic and conventional cholecystectomy. Didactic concept for training and
      introduction of laparoscopic cholecystectomy and preventing complications].
AB  - AIM: This study has assessed the suitability of an educational concept for the
      introduction and training of laparoscopic cholecystectomy, a newly established
      operational procedure, within an university teaching hospital with a large number
      of surgeons. PATIENTS AND METHODOLOGY: Since introduction of the first
      laparoscopic cholecystectomy all cholecystectomies were prospectively assessed
      over a period of two years (from May 1990 till May 1992). The educational concept
      applied was such that a given surgeon would first receive training from an
      instructor for 15 procedures and then assume responsibility for instruction of a
      subsequent trainee. RESULTS: In two years 355 patients underwent cholecystectomy.
      60% of the operations were performed laparoscopically and 40% of the operations
      performed openly. During the two year period 13 surgeons were trained in the new
      technique, with an average of 16 operations per surgeon. Throughout the
      introductory phase there were no serious complications, and in particular no
      damage to the bile duct. DISCUSSION: The advantage of this introductory training
      phase has repeatedly been subject of discussion in the literature. In the
      meanwhile guidelines from specialist bodies and national institutions exist for
      regulating the education of new surgical techniques. In the past few years
      introduction to new techniques has gradually shifted toward training on the skill
      stations and virtual reality trainers. CONCLUSION: The described educational
      concept for the introduction and training of laparoscopic cholecystectomy has
      been well approved and accepted since the early 90's.

PMID- 12520844
TI  - Pilonidal sinus: how to choose between excision and open granulation versus
      excision and primary closure? Study of a series of 141 patients operated on from
      1991 to 1995.
AB  - AIMS: The purpose of this study was to evaluate excision and open granulation
      versus excision and primary closure as treatments for pilonidal sinus. SUBJECTS
      AND METHODS: We evaluated a group of 141 patients operated on for a pilonidal
      sinus between 1991 and 1995. Ninety patients were treated by excision and open
      granulation, 34 patients by excision and primary closure and 17 patients by
      incision and drainage, as a unique treatment of an infected pilonidal sinus.
      RESULTS: The first group, receiving treatment of excision and open granulation,
      experienced the following outcomes: average length of hospital stay, four days;
      average healing time; 72 days; average number of post-operative ambulatory
      visits, 40; average off-work delay, 38 days; and average follow-up time, 43
      months. There were five recurrences (6%) in this group during the follow-up
      period. For the second group treated by excision and primary closure, the
      corresponding outcome measurements were as follows: average length of hospital
      stay, four days; average healing time, 23 days; primary healing failure rate, 9%;
      average number of post-operative ambulatory visits, 6; average off-work delay, 21
      days. The average follow-up time was 34 months, and two recurrences (6%) were
      observed during the follow-up period. In the third group, seventeen patients
      benefited from an incision and drainage as unique treatment. The mean follow-up
      was 37 months. Five recurrences (29%) were noticed, requiring a new operation in
      all the cases. DISCUSSION AND CONCLUSION: This series of 141 patients is too
      limited to permit final conclusions to be drawn concerning significant advantages
      of one form of treatment compared to the other. Nevertheless, primary closure
      offers the advantages of quicker healing time, fewer post-operative visits and
      shorter time off work. When a primary closure can be carried out, it should be
      routinely considered for socioeconomical and comfort reasons.

PMID- 12520845
TI  - [Brain concussion: risk factors].
AB  - AIM: Identification of risk factors for intracranial bleeding after minor
      traumatic brain injury. METHOD: The charts of 464 patients treated between
      January 1976 and December 1997 with the initial diagnosis of minor traumatic
      brain injury were reviewed. They were analyzed for clinical and diagnostic signs
      putting the patients at risk for intracranial bleeding. RESULTS: About two thirds
      of the patients (67.5%) were males, the average age being 36.1 years. Leading
      causes of accident were sudden falls (27.4%) and bike/autocycle crashes (24.8%).
      30.4% of the patients were under the influence of alcohol. At the time of
      admission to the hospital 17.2% of the patients showed impaired consciousness and
      12.5% presented neurologic signs. In ten patients an intracranial bleeding was
      found. All these bleedings were diagnosed at the primary investigation.
      DISCUSSION/CONCLUSIONS: Following groups of patients with traumatic brain injury
      have an increased risk for intracranial bleeding: Age > 60 and < 16 years, sudden
      falls, tachycardia, Glasgow-Coma-Scale < 15, impairment of consciousness,
      neurologic signs, fracture of the skull and patients suffering from coagulopathy.
      Drunk patients are difficult to judge; therefore, they should be handled as being
      at risk. Patients at increased risk should be observed on an intensive care unit
      whereas patients without those risk factors can be observed on a normal ward or,
      alternatively, discharged after reexamination and uneventful course after some
      hours.

PMID- 12520846
TI  - [Vacuum sealing of problem wounds].
AB  - Within the scope of a retrospective study, the efficiency of the vacuum sealing
      technique, a recent alternative to methods used in treatment of both chronic or
      acute infected wounds and acute traumatic soft tissue defects, was evaluated in
      120 patients in the period between January 1995 and November 1997. The vacuum
      sealing technique offers an effective therapeutic option for the temporary
      closure of defect as well as of infected wounds, decreases the risk of wound
      infection and offers advantage regarding patient's comfort and hospital hygiene.

PMID- 12520847
TI  - Stromal tumor in a perforated Meckel's diverticulum: a case report.
AB  - Stromal tumors are rare neoplasms of the small bowel that locate in Meckel's
      diverticulum with high preference. Perforation of those tumors is very uncommon.
      There are 96 cases reported in current literature, including only 6 perforations.
      The diagnosis of that kind of tumor is very difficult because of lack of
      pathognomonic signs and symptoms. The clinical presentation include abdominal
      pain, intestinal bleeding, abdominal mass, intestinal obstruction and less
      commonly, acute perforation. We report the case of a 61-years old patient with a
      poorly differentiated stromal tumor in a perforated Meckel's diverticulum. The
      difficulty of identifying a stromal tumor preoperatively and the therapeutic
      options are emphasised. It is suggested that an aggressive attitude should be
      taken in the preoperative management of any patient over 50 years of age who
      presents with melena and abdominal pain.

PMID- 12520848
TI  - [Solitary duodenal diverticulum with enterolith as a rare cause of acute
      abdomen].
AB  - Diverticula of the duodenum are not rare and in the most cases without any
      symptoms. The incidence of duodenal diverticula in autopsies is known to be 20
      22%. Only in a very small number of cases, they are complicated and therefore
      clinically presented by diverticulitis, perforation, hemorrhage, pancreatitis, or
      biliary obstruction. The most uncommon complication is the enterolith formed
      within the diverticulum. In all reported cases, the enterolith--formation was
      associated with small bowel obstruction or perforation. Complications of duodenal
      diverticula have a high mortality rate (33-48%) that could be due to difficulties
      in diagnostics and the adequate surgical procedure. In our case report, a patient
      presented at our institution with symptoms of an acute abdomen caused by an
      enterolith inside a solitary duodenal diverticulum "ante perforationem". The
      ultrasound and the CT scan of the abdomen showed free intraabdominal fluid beside
      the duodenum, the exact diagnosis however was not made. The indication for
      laparotomy was given by the clinical signs. The dicerticula was resected and
      ligated.

PMID- 12520849
TI  - [Acute ischemia of the hand in a drug addict after accidental intra-arterial
      injection].
AB  - We report a case of a 31-year-old male drug addict with acute ischaemia of the
      right hand after inadverted intraarterial injection of suspended tablets into
      brachial artery. He was successfully treated with intraarterial administration of
      urokinase (250'000 IU as bolus, then continuous infusion of 250'000 IU per 12
      hours), papaverin (40 mg i.v. 3 x every 4 hours), systematic heparinisation and
      with axillary plexus anesthesia (Bupivacain 0.25%, 10 ml/h). Treatment options
      are discussed reviewing recent publications. Early onset of treatment is
      mandatory for a good outcome.

PMID- 12520850
TI  - [Prevention of thromboembolism in conservative ambulatory fracture treatment.
      Verification of an out-of-court FMH (Federation Mediation Helvetica) expert
      assessment].
AB  - In an extra judicial assessment for the Medical Assessment Centre of the FMH
      (Federation Mediation Helvetica) a clinical case of a female patient who had
      suffered from deep vein thrombosis was reviewed. The patient had been treated
      conservatively for a malleolar fracture and had not received any pharmaceutical
      thrombosis prophylaxis. The question of false treatment had to be discussed. The
      final conclusion of the judicial assessment is that the medical treatment with a
      physical thrombosis prophylaxis of the patient was correct. Due to the various
      controversial judgements found in the literature concerning the thrombosis
      prophylaxis, a certain insecurity remains for the treating physician. Taking into
      account the different risk factors, the indication for a prophylaxis must
      therefore still be decided on an individual basis.

PMID- 12520851
TI  - [Role of nutritional care in hospitals in the prevention of disease-related
      malnutrition].
AB  - The prevalence of undernutrition is about 30% at admission to hospitals, and in
      many cases the nutritional risk is not recognized and significantly increases in
      patients during hospitalisation in Hungary. Undernutrition and acute rapid weight
      loss of as little as 2-3 kg (cc. 5%) in combination with disease increases the
      risk of complications, lowers resistance to infection, impairs physical and
      mental functioning and delays recovery. Undernourished patients are at greater
      risk for adverse medical outcomes than well-nourished ones. In most hospitals the
      nutritional risk of patients is not determined and nutritional treatment plan
      isn't developed; fewer than 10 Nutritional Support Teams are established in
      hospitals. Nutritional care of ill patients is considered as a part of clinical
      treatment in very few hospitals in Hungary. There is no adequate recognition of
      the problem of undernutrition. The simplest and safest way to provide nutritional
      support is the adequate energy rich oral nutrition. If the oral nutrition fails
      or is inappropriate then artificial nutritional support becomes necessary.
      Nutrition is the most cost effective measure to prevent the complications of
      diseases. To improve the intolerable situation it would be necessary to increase
      the nutritional knowledge and the awareness of health care teams of the real
      importance of nutritional status in illnesses, and improve the quality of
      hospital food and eating conditions and environment.

PMID- 12520852
TI  - [Diabetes insipidus: etiology, diagnosis, and therapy].
AB  - Diabetes insipidus is a disorder of the water retaining ability of the organism.
      It is a polydipsic-polyuric syndrome caused by partial or complete vasopressin
      deficiency (central diabetes insipidus) or vasopressin resistance of the kidney
      tubules (nephrogenic diabetes insipidus) or increased water intake due to
      oversensitivity of the thirst centre (dipsogenic diabetes insipidus = primary
      polydipsia). The pathogenetic factors may affect the osmoreceptors, the
      vasopressinergic magnocellular nuclei of the hypothalamus, the median eminence,
      the pituitary stalk, the vasopressin release from the neurohypophysis, the
      vasopressin inactivating mechanisms and the renal structures mediating the
      antidiuretic effect of vasopressin. In the evaluation of the results of the
      diagnostic procedures, it is to be considered that long-term overhydration of any
      origin suppresses the vasopressin secretion and the "washout" effect of the long
      term water-diuresis decreases the concentration gradient of the renal medulla
      leading to blunted sensitivity towards vasopressin. This is, why the differential
      diagnostics of central, nephrogenic and dipsogenic diabetes insipidus seems
      sometimes to be enigmatic. Central diabetes insipidus can be excluded only on the
      basis of proportional parallel increase of plasma osmolality and plasma
      vasopressin level. Similarly, nephrogenic diabetes insipidus will be excluded
      when plasma vasopressin increases proportionately with the increase of urinary
      osmolality. In equivocal cases T1-weighted MRI of the pituitary may be of help in
      the establishment of an exact diagnosis. As far as possible, the therapy is to be
      focused on the diabetes insipidus evoking basal diseases. In central diabetes
      insipidus, diuresis can be decreased by vasopressin substitution. The first
      choice compound for this purpose is 1-desamino-8-D-arginine-vasopressin. The non
      vasopressin containing oral antidiuretics have become outdated in the treatment
      of central diabetes insipidus. There is no specific treatment for nephrogenic and
      dipsogenic diabetes insipidus, so far. Nephrogenic diabetes insipidus can be
      influenced by non-steroidal antiinflammatory agents or diuretics. Their combined
      administration is even more effective, however, still does not exceed a 50
      percent mitigation in diuresis.

PMID- 12520853
TI  - [Possibilities for correction of n-3 fatty acids insufficiency in the Hungarian
      population].
AB  - Long since several experiences have proved that the diverse fatty acids
      significantly differ in their effects on the human organism. These differences
      originate in the variety of the structure of the fatty acids, and the diverse
      structures are reflected in significantly diverse physical, chemical and
      biological characteristics. Among different fatty acids, n-6 and n-3 essential
      fatty acids are very important. Since they have had a vital importance in respect
      of growth, development and body functions, the population's food has to contain
      both fatty acids in a satisfactory amount. According to a general opinion, our
      national diet contains n-6 fatty acids in a proper amount: however, it is largely
      insufficient in n-3 fatty acids. Therefore, this unfavourable situation should be
      improved by a considerable increase of our consumption of n-3 fatty acids. The
      author has presented presumable reasons of this deficiency, and has highlighted
      that production, marketing and consumption of special 'functional foods', rich in
      n-3 fatty acids may considerably improve this unfavourable situation.

PMID- 12520854
TI  - [Investigation of the gene locus in autosomal polycystic kidney disease in a 21
      year old female patient with congenital hepatic fibrosis and polycystic liver].
AB  - BACKGROUND: Congenital hepatic fibrosis is an uncommon cause of portal
      hypertension in childhood or the early adolescence, usually presented with
      hepatomegaly and bleeding from esophageal varices. Despite the hepatomegaly and
      the fibrotic reconstruction of the liver the liver function tests are usually
      normal. In most cases it is associated with cystic disease of the kidneys.
      Congenital hepatic fibrosis is a constant feature of autosomal recessive
      polycystic kidney disease. CASE: The authors report on the case of a female
      patient with polycystic kidneys and polycystic liver. The symptoms of portal
      hypertension presented in the age of 20, on the basis of liver biopsy congenital
      hepatic fibrosis was diagnosed. AIMS: The authors intended to investigate whether
      there is genetic alteration as common etiology behind the rare association of
      congenital hepatic fibrosis confirmed in the adolescence and the polycystic
      disease of the liver and the kidneys. The clinical manifestation raised the
      possibility of autosomal recessive polycystic kidney disease. Segregation of
      microsatellite markers for autosomal recessive polycystic kidney disease gene
      locus 6p21.1-p12 was examined in the affected family to assess the possible role
      of theis gene. RESULTS: Four out of the 6 polymorphic microsatellite markers were
      informative, indicating that the autosomal recessive polycystic kidney disease
      may be responsible for the development of the rare association of the lesions of
      the liver and the kidneys in authors' patient.

PMID- 12520855
TI  - [Public health in Southern Transdanubia of Hungary during the era of dualism].

PMID- 12520856
TI  - [Medicine and history].

PMID- 12520857
TI  - Opinions about 'unexplained subfertility'.
AB  - The term 'unexplained subfertility' applies to the situation in which a couple,
      despite serious attempts, does not achieve pregnancy, while according to current
      knowledge no physiological or anatomical abnormalities can be found. In this
      paper, possible causes of this phenomenon are reviewed and opinions of six
      doctors working in the field of reproductive medicine are described. The most
      significant finding of this study is that all doctors hold personal views with a
      high level of certainty about the causes of unexplained subfertility. However,
      they hardly agree with each other! In conclusion, in the field of reproductive
      medicine there is a dangerous combination of strong personal opinions and much
      disagreement with regards to unexplained infertility.

PMID- 12520858
TI  - Munchausen syndrome in obstetrics and gynecology.
AB  - Munchausen syndrome (MS) is a well-defined clinical psychiatric entity.
      Furthermore, it is a complicated and intriguing problem in medicine in general
      and in obstetrics and gynecology in particular. The proportion of MS cases in
      obstetrics and gynecology is rising. This review covers relevant reports from the
      last four decades. Emphasis is put on the clinical expression of MS cases in
      obstetrics and gynecology. A discussion about their validity as such is included.
      Awareness of attending physicians to this type of illness in the era of patient
      rights, on the one hand, and the existence of defensive medicine on the other, is
      crucial.

PMID- 12520859
TI  - Gendered personality dispositions, hormone values, and hot flushes during and
      after menopause.
AB  - The study aim was to test the relationship between gendered personality
      dispositions (GPD), sex hormones, and vasomotor complaints in the menopausal
      transition. Fifty-seven healthy women (mean age 51.1 years, standard deviation
      2.0) were drawn from a population registry. At enrollment all women were
      menstruating regularly, and all women reached menopause in the course of the
      study. Questionnaire data and blood samples were collected once a year over a
      period of five years. GPD scores (based on the Bem Sex-Role Inventory, BSRI),
      frequencies of hot flushes and hormone data (estradiol, follicle-stimulating
      hormone, luteinizing hormone, testosterone, androstendione and
      dehydroepiandrostendione sulfate) were determined. Subjects were placed into four
      categories based on the BSRI: masculine, feminine, androgynous and
      undifferentiated. GPD did not change during the menopausal transition.
      Testosterone and androstendione were related to GPD in that testosterone and
      androstendione were higher in the sex typed categories (masculine and feminine)
      than in the non sex-typed categories (androgynous and undifferentiated). GPD are
      related both to androgens and to vasomotor complaints such as hot flushes during
      the menopausal transition, but the mechanisms of these relationships are not
      known.

PMID- 12520860
TI  - Fear of childbirth during pregnancy: a study of more than 8000 pregnant women.
AB  - In today's modern obstetrics, perinatal morbidity and mortality of mother and
      neonate have become extremely rare. Despite these advances, are pregnant women
      still afraid of childbearing and, if so, what--and how intense--are their fears?
      Are these fears influenced by previous birthing experiences and by birth
      preparation classes? Data from more than 8000 expectant mothers (collated via a
      prenatal questionnaire distributed between November 1, 1991 and October 31, 1999)
      are evaluated. This study examines and discusses the answers concerning quantity
      and quality of childbirth-related fear among women of differing parity and its
      possible relation to attended birth preparation classes. The women delivered in a
      hospital setting that practices modern obstetrics combined with alternative
      delivery methods. The most frequent fears mentioned are fear for the child's
      health (50%) and fear of pain (40%). Fears dealing with medical intervention,
      such as operative delivery, anesthesia, nerve blockage and of being at the mercy
      of obstetrics all lie at around 12%. It is difficult to establish a clear-cut
      benefit of birth preparation classes in reducing childbirth fears.

PMID- 12520861
TI  - An exploration of the nature and causes of distress in women attending gynecology
      outpatient clinics.
AB  - This study evaluates the distress experienced by women attending gynecology
      outpatient clinics (GOCs). We investigate causes of this distress and explore
      women's own experience of their distress. A questionnaire survey of 197 women
      attending GOCs was carried out, both quantitative and qualitative analyses were
      undertaken. Thirty-five percent of women showed clinical levels of anxiety, 13%
      had clinically significant depression and half reported feeling distressed. A
      range of feelings was reported, though commonly mixed emotions were expressed.
      Women had a low sense of personal control and uncertainty in relation to their
      gynecologic problem. Both coincidental stress, such as life changes, and the
      direct consequences of the gynecologic problem were predictive of anxiety.
      Qualitative analysis suggested four ways in which women experienced their
      distress and the gynecologic problem: (i) gynecologic symptoms were a direct
      cause of distress, (ii) gynecologic symptoms caused distress indirectly through
      reactions to diagnosis and treatment, (iii) gynecologic symptoms caused distress
      because of their impact on relationships, social life and self identity, and (iv)
      distress was unrelated to the gynecologic symptoms. Results highlight diversity
      and complexity in women's experiences and support the need for a fuller
      understanding of distress in this group in order to meet their needs adequately
      and appropriately.

PMID- 12520862
TI  - Gender and unwanted pregnancy: a community-based study in rural Ghana.
AB  - This study investigates attitudes concerning unwanted pregnancies in a rural
      district of western Ghana. Structured questionnaires were used to interview men
      and women between 15 and 49 years of age (n = 2179) to measure the prevalence of
      unwanted pregnancy, how often it led to induced abortion and to establish the
      reasons why a pregnancy was considered unwanted. At some time in their life at
      least one unwanted pregnancy was experienced by 41% of men and 43.6% of women.
      Men and women reported a similar proportion of pregnancies (17.3% and 16.1%,
      respectively) as unwanted. The proportion of unwanted pregnancies terminated by
      induced abortion varied with the reason why the pregnancy was undesirable. Among
      both men and women socio-economic problems were most commonly cited with unwanted
      pregnancies. Pregnancies perceived by women as unwanted ended more often in an
      induced abortion than those unwanted by men. Reproductive health programs need to
      make contraceptives available, accessible and acceptable for both women and men.
      More research is needed to facilitate a clear understanding of the impact of
      gender on unwanted pregnancy and its prevention.

PMID- 12520863
TI  - Variables influencing anxiety of patients with abnormal cervical smears referred
      for colposcopy.
AB  - The state anxiety scores of women with abnormal cervical smears referred for
      colposcopy were investigated to identify causes of anxiety, factors influencing
      anxiety and emotions involved with anxiety, in order to define strategies to
      reduce this anxiety. Forty-seven women were interviewed and completed a
      questionnaire and the Spielberger State and Trait Anxiety Inventory (STAI): 22
      women prior to their intake consultation at the colposcopy clinic of the
      University Medical Center St Radboud, Nijmegen, and 25 women during their second
      visit before the actual colposcopy. The mean State anxiety score was 48.2,
      without significant differences between the intake and colposcopy consultation.
      The majority experienced anxiety because of a fear of cancer and/or the
      colposcopy. The mean State anxiety score was significantly higher in women who
      considered the level of information provided by the gynecologist/family
      practitioner insufficient, who experienced a long waiting time, who did not have
      a partner, and who experienced additional emotions like anger and sadness. In
      conclusion, patients referred for colposcopy after an abnormal cervical smear
      result have high levels of anxiety. High levels of anxiety may be reduced by
      uniform and explicit information about cervical smear results and colposcopy, by
      reduction of clinic waiting times, by stimulating social support, and by
      attention to emotions like anger and sadness.

PMID- 12520864
TI  - Sexuality and globalization.

PMID- 12520865
TI  - Euthanasia--or, death on request.

PMID- 12520866
TI  - [Hemoglobin, from microorganisms to man: a single structural motif, multiple
      functions].
AB  - Haemoglobins from unicellular organisms, plants or animals, share a common
      structure, which results from the folding, around the heme group, of a
      polypeptide chain made from 6-8 helices. Nowadays, deciphering the genome of
      several species allows one to draw the evolutionary tree of this protein going
      back to 1800 millions of years, at a time when oxygen began to accumulate in the
      atmosphere. This permits to follow the evolution of the ancestral gene and of its
      product. It is likely that, only in complex multicellular species, transport and
      storage of oxygen became the main physiological function of this molecule. In
      addition, in unicellular organisms and small invertebrates, it is likely that the
      main function of this protein was to protect the organism from the toxic effect
      of O2, CO and NO*. The very high oxygen affinity of these molecules, leading them
      to act rather as a scavenger as an oxygen carrier, supports this hypothesis.
      Haemoglobins from microorganisms, which may probably be the closest vestiges to
      the ancestral molecules, are divided into three families. The first one is made
      from flavohaemoglobins, a group of chimerical proteins carrying a globin domain
      and an oxido-reduction FAD-dependant domain. The second corresponds to truncated
      haemoglobins, which are hexacoordinated with very high oxygen-affinity molecules,
      20-40 residues shorter than classical haemoglobins. The third group is made from
      bacterial haemoglobins such as that of Vitreoscilla. Some specific structural
      arrangements in the region surrounding the heme are cause of their high oxygen
      affinity. In plants, two types of haemoglobins are present (non-symbiotic and
      symbiotic), that arose from duplication of an ancestral vegetal gene. Non
      symbiotic haemoglobins, which are probably the oldest, are scarcely distributed
      within tissues having high energetic consumption. Conversely, symbiotic
      haemoglobins (also named leghaemoglobins) are present at a high concentration
      (mM) mostly in the rhizomes of legumes, where they are involved in nitrogen
      metabolism. In some species, haemoglobin was proposed to be an oxygen sensor
      bringing to the organism information to adjust metabolism or biosynthesis to the
      oxygen requirement. Elsewhere haemoglobin may act as final electron acceptors in
      oxido-reduction pathways. Evolution of haemoglobin in invertebrates followed a
      large variety of scenarios. Some surprising functions as sulphide acquisition in
      invertebrates living near hydrothermal vents, or a role in the phototrophism of
      worm need to be mentioned. In invertebrates, the size of haemoglobin varies from
      monomers to giant molecules associating up to 144 subunits, while in vertebrates
      it is always a tetramer. In some species, several haemoglobins, with completely
      different structure and function, may coexist. This demonstrates how hazardous
      may be to extrapolate the function of a protein from only structural data.

PMID- 12520867
TI  - [Multilocus allozyme differentiation of populations of the mussel Mytilus
      galloprovincialis Lmk. from Moroccan coasts].
AB  - Along the Moroccan coasts, the systematic status of Mytilus populations have been
      for a long time uncertain and confused, due to the use of unreliable morphometric
      criteria. In the present study, allozyme markers reveal the exclusive existence
      of M. galloprovincialis on Mediterranean and Atlantic coasts. Nei's genetic
      distances are low and reflect a high gene flow between Atlantic and Mediterranean
      populations. However, a significant multilocus discontinuity revealed by F
      statistics separate southern Atlantic populations from Mediterranean and north
      Atlantic ones and could be explained by a gene flow breaking because of a larval
      dispersal decrease, due to a sea surface current direction change from Cap Ghir
      towards the Canaries archipelago, and probably by differential selection effects
      in these two geographic areas.

PMID- 12520868
TI  - Evolution of freezing susceptibility and freezing tolerance in terrestrial
      arthropods.
AB  - Arthropods have evolved various adaptations to survive adverse seasons and it has
      long been discussed why some arthropods are freezing-susceptible and some are
      freezing-tolerant. However, which mode of frost resistance came first during the
      course of evolution? A commonly held opinion is that no choice of strategy has
      been offered in evolution, because each species of arthropod may have its own
      evolutionary and natural history, leading to cold-hardiness. Freezing tolerance
      is more frequent in holometabolous insect orders and partially used by certain
      vertebrates, like some terrestrially hibernating amphibians and reptiles.
      Supported by phylogenetic, ontogenetic and ecological arguments, we suggest here
      that freezing tolerance is more recent than freezing susceptibility in the course
      of arthropods evolution. In addition, we observe that three basic modes of
      freezing resistance in insect species exist in the field: (i) permanent or year
      round freezing-susceptible species, (ii) alternative or seasonal freezing
      susceptible/freezing-tolerant species, (iii) permanent or year-round freezing
      tolerant species.

PMID- 12520869
TI  - Assessment of otocephalan and protacanthopterygian concepts in the light of
      multiple molecular phylogenies.
AB  - The rise of cladistics in ichthyology has dramatically improved our knowledge of
      teleostean basal interrelationships. However, some questions have remained open,
      among them the reliability of the Otocephala, a clade grouping clupeomorphs and
      ostariophysans, and the relationships of the Esocoidei. These two questions have
      been investigated in the light of new DNA sequences (from 28S and rhodopsin
      genes) and sequences from data banks (cytochrome b, 12-16S, 18S, MLL and RAG1).
      The ability of each of these markers to resolve basal teleostean
      interrelationships is assessed, and the cytochrome b was not found appropriate.
      Practical (i.e. different taxonomic samplings) and epistemological grounds led us
      to perform multiple separated phylogenetic analyses, in order to estimate the
      reliability of the above clades from their repeatability among trees from
      independent sequence data. The Otocephala are found monophyletic from most of the
      datasets; otherwise, they are not significantly contradicted from the others,
      which exhibit unresolved relationships. We conclude that the evidence provided
      here favours the sister-group relationship of clupeomorphs and ostariophysans.
      Morphological evidence including fossils is discussed, concluding that
      morphological works have not yet provided sufficient data to support this group.
      Salmonids and esocoids are found sister-groups from every molecular dataset in
      which these groups were sampled. Based on these convincing results, the
      Protacanthopterygii of Johnson and Patterson [1] are redefined, including the
      Esocoidei.

PMID- 12520870
TI  - The effect of hydrostatic pressure on biological systems.

PMID- 12520871
TI  - The analytical ultracentrifuge as a probe for interface transport phenomena.

PMID- 12520872
TI  - TransChromo Mouse.

PMID- 12520873
TI  - Marrow stromal stem cells for repairing the skeleton.

PMID- 12520875
TI  - Preventing sexual transmission of HSV and HIV: the challenge for active and
      passive immunization of mucosal surfaces.

PMID- 12520874
TI  - A super-channel in bacteria: macromolecule uptake and depolymerization systems of
      Sphingomonas sp. A1 with a special cell surface structure.

PMID- 12520876
TI  - Engineered commensal bacteria as delivery systems of anti-infective mucosal
      protectants.

PMID- 12520877
TI  - Recent developments in the production of novel polyketides by combinatorial
      biosynthesis.

PMID- 12520878
TI  - A rational design approach for developing immunomodulators based on CD4 and CD8.

PMID- 12520879
TI  - Prospects for an HIV vaccine: conventional approaches and DNA immunization.

PMID- 12520880
TI  - Viruses as vectors for the expression of foreign sequences in plants.

PMID- 12520881
TI  - Nitric oxide and reactive nitrogen oxide species in plants.

PMID- 12520882
TI  - Bioengineered rice for plant protection.

PMID- 12520883
TI  - The self-assembly and structure of caseins in solution.

PMID- 12520885
TI  - A phenomenology of closeness and its application to sexual boundary violations: a
      framework for therapists in training.
AB  - Sexual boundary violations remain a persistent problem in psychiatry despite
      increased attention, disciplinary activity, and educational efforts. Currently,
      therapists in training are often overwhelmed by a sense of danger in every
      direction, including the risk of false accusation. The authors present a
      framework for understanding experiences of closeness that can help overcome a
      trainee's paralyzing bewilderment and attendant longing to retreat from the
      practice of psychotherapy. Eight characteristics of ordinary psychotherapeutic
      engagement effectively maximize the intensity of interpersonal closeness between
      patient and psychotherapist while simultaneously reducing the experience of
      closeness outside the treatment setting for both patient and clinician. An
      important consequence is that drifts toward sexual boundary violations can arise
      from the everyday dynamics of closeness, even in the absence of individual
      pathology or intent. The implications for the practice of psychotherapy and
      personal lives of psychotherapists are explored.

PMID- 12520884
TI  - Envy and jealousy.
AB  - Clinical study of envy and jealousy in the psychotherapy situation indicates that
      these two states of mind are biopsychosocial response patterns involving the
      perceptual, cognitive, affective, and intentional mental functions. These
      response patterns are evoked by perceptual events that inform the individual of
      one's relative position vis-a-vis the requirements of one's life. Once these
      patterns can be discerned in the patient, the clinician is able to bear things in
      the psychotherapy situation not previously heard and understand, interpret, and
      work through conflict in a new and useful way. In this paper psychotherapy
      paradigms and strategies are discussed from the new perspective afforded by the
      psychology of envy and jealousy.

PMID- 12520886
TI  - False accusations: genesis and prevention.
AB  - Professionals engaged in trust relationships can become the target of false
      allegations in courts and ethics committees. An allegation is considered false
      when it is not possible to establish a direct and clear causal link between
      actions (or inactions) of the accused and damage sustained by the accuser. Long
      term psychotherapy allows a unique setting to observe and document the formation
      of false allegations in slow motion over time. Expert witness work can be likened
      to a detailed analysis of a battery of psychological tests in which a profile of
      abusive experiences spanning a lifetime can be constructed to demonstrate the
      likelihood that the current allegation is false. In such instances the accuser
      confuses in transference the perpetrator of past abuse with the person in the
      present trust relationship. Guidelines for prevention of false accusations in
      professional practice are suggested.

PMID- 12520887
TI  - Treating Haitian patients: key cultural aspects.
AB  - The Haitian community in the United States is growing steadily. They make up a
      significant portion of many cities. As a group, Haitian immigrants are a
      challenge to mental health professionals. Their view and concepts of the world
      are unique. Non-Haitian clinicians need to be knowledgeable of the culture in
      order to provide competent care. The goal of this article is to help clinicians
      understand aspects of Haitian culture that will facilitate mental health
      treatment. A historical perspective is offered since the history of Haiti has
      shaped society, families and therefore individuals. The role of the supernatural
      is addressed to provide a better understanding of the Haitian psyche. The
      political and economic climate in Haiti has led to a significant increase in the
      number of Haitians migrating to the United States. Haitians are faced with the
      challenge of adapting to a new culture; they experience stress and become
      vulnerable to mental illness. As a result, there is increasing demand for mental
      health services. This article highlights aspects of Haitian culture relevant to
      mental health clinicians. It provides an overview of Haitians' attitudes toward
      mental health and the utilization of psychotherapy. Concepts relevant to Voodoo
      beliefs and practices are discussed since these beliefs can shape attitudes, and
      compliance with treatment. Recommendations for engaging and maintaining Haitian
      clients in psychotherapy are made. Case vignettes are provided for illustration.

PMID- 12520888
TI  - The role of couple therapy in the treatment of narcissistic personality disorder.
AB  - Recommendations for psychotherapeutic management of patients with narcissistic
      personality disorder are based on clinical experience; however, little attention
      has been given to the role of couple therapy with these patients. A stable
      intimate relationship appears to positively affect the course and outcome of
      narcissistic personality disorder. Based on clinical experience with narcissistic
      individuals in couple therapy and using a psychoanalytic framework, three
      characteristics that differentiate couples who will from those who will not
      benefit from couple therapy are described. These characteristics are the ability
      of the narcissistic individual to curtail acting out, the narcissistic
      vulnerability as evidenced by their level of defensiveness, and the couple's
      complementarity of narcissistic gratification. Two clinical examples are given to
      demonstrate the usefulness of the proposed characteristics in deciding on the
      appropriateness of couple therapy.

PMID- 12520889
TI  - Contribution of defensive functioning to the quality of working alliance and
      psychotherapy outcome.
AB  - We analyzed whether defense mechanisms changed and/or predicted outcome during
      brief dynamic psychotherapy (N = 43, max 40 sessions, Norwegian Multisite Study
      on Process and Outcome of Psychotherapy). Defenses were rated with the Defense
      Mechanism Rating Scales (DMRS, clinician-rated) and Defense Style Questionnaire
      (DSQ self-rated). Overall defensive functioning (ODF) as rated by DMRS changed
      significantly. We found that the initial ODF's neither predicted the quality of
      working alliance nor influenced the outcome. Symptoms improved most rapidly early
      in therapy, while defenses changed during the last half of therapy, consistent
      with the phase model of change.

PMID- 12520890
TI  - Depression after cardiac transplant treated with interpersonal psychotherapy and
      paroxetine.
AB  - This case study discusses the treatment of a 67-year-old man with no prior
      history of psychiatric illness diagnosed with major depression following cardiac
      transplantation. Shortly after surgery, the patient demonstrated depressive
      symptoms, including weight loss, emotional instability, and social isolation.
      Psychiatric consultation revealed that the patient first experienced these
      symptoms after learning that the donor heart he had received belonged to a woman.
      The patient had preconceived, stereotypical ideas that a woman's heart would
      inhibit his physical recovery and transform him into a more emotional man. The
      patient was prescribed the selective serotonin reuptake inhibitor paroxetine and
      began interpersonal psychotherapy. Results from this case study indicate that
      treatment with paroxetine, combined with interpersonal psychotherapy, may be
      successful in treating patients who had transplants and suffer from postsurgical
      depression.

PMID- 12520891
TI  - Posttraumatic stress disorder (PTSD) after heart transplant: the influence of
      earlier loss experiences on posttransplant flashbacks.
AB  - The incidence of posttraumatic stress disorder (PTSD) after heart transplant is
      about 17%, making it an important psychosocial complication. This case study
      discusses the relationship between early traumatizing experiences of loss and the
      lead symptoms of PTSD (e.g., flashbacks, nightmares). It is demonstrated how the
      encoding of a traumatic experience into existing representations leads not only
      to a reactivation of an earlier trauma, but may constitute a protective function
      in the processing of a PTSD.

PMID- 12520892
TI  - Family therapy and dialectical behavior therapy with adolescents: Part I:
      Proposing a clinical synthesis.
AB  - Although the practice of family therapy in dialectical behavior therapy (DBT)
      with multiproblem suicidal adolescents is common and generally indicated, a
      particular model has yet to be delineated with this age group. The purpose of
      this article is to propose a coherent clinical synthesis of the more individually
      oriented DBT strategies with a broader family-systems orientation that maintains
      the integrity of both theoretical approaches while addressing the treatment needs
      of adolescents and their families. First, the authors briefly review the
      literature. Second, they describe the core dialectic of DBT, balancing acceptance
      and change, and its relevance to family therapy. Finally, the authors propose
      several specific acceptance and change strategies useful when implementing DBT
      family therapy with multi-problem adolescents.

PMID- 12520893
TI  - Family therapy and dialectical behavior therapy with adolescents: Part II: A
      theoretical review.
AB  - Dialectical Behavior Therapy (DBT) is based on a transactional model of the
      etiology of borderline personality disorder (BPD). It assumes that the associated
      emotional dysregulation is not simply biological or family induced but the result
      of a dynamic interaction between the biology and characteristics of an individual
      with the individual's social environment. This paper discusses the theoretical
      issues and empirical research relating to a synthesis of family therapy and DBT
      with adolescents. A review of the literature identifies support for a greater
      understanding and inclusion of families in treatment, attention to relational
      aspects of affect, and a dialectical framework for synthesizing individual
      oriented and systemic-oriented theories and practice. Some implications for the
      development of a DBT family therapy model are discussed.

PMID- 12520901
TI  - [Public health service and occupational medicine].
AB  - The article tackles problems of public health development, role of industrial
      hygiene to coordinate public efforts on preservation of national occupational
      resources. The authors formulated main activity trends of occupational medicine
      to specify public policy on workers' health preservation, on creation of
      favorable working environment, on increase of public activities to health
      preservation at workplace, methods of health services' reorientation for the
      problem solution.

PMID- 12520902
TI  - [Occupation-related compression neuropathies of the lower limbs].
AB  - Occupational medical examinations and hospital studies considered prevalence and
      clinical features of compression neuropathies of lower limbs in workers subjected
      to static and dynamic overload of legs. Findings are locomotory and vascular
      disorders causing compression of peripheral nerves.

PMID- 12520903
TI  - [Some features of gastric disorders in occupational diseases].
AB  - Some features were revealed after study of 185 patients with various occupational
      diseases: chronic lead intoxication, bronchial asthma, and disorders caused by
      fluor. Considering polyetiology and nonspecificity of gastric diseases, the
      authors could not determine the changes revealed as caused only by occupational
      exposure.

PMID- 12520904
TI  - [Early clinical and laboratory signs of exposure to nickel in electroplating shop
      workers].
AB  - The authors studied diagnostic value of biochemical, immunologic parameters in
      workers exposed to lower levels of nickel. Suggestion is a complex of
      characteristics having the highest sensitivity and appropriate in screening for
      early changes in health state of workers exposed to nickel.

PMID- 12520905
TI  - [Role of genetic blood markers (ABO-HLA systems) in the formation of increased
      sensitivity to occupational allergen epichlorohydrin].
AB  - The authors demonstrated that genetic factors play the certain role in
      hypersensitivity to occupational allergen epichlorohydrin. The sensibilized
      workers demonstrated higher incidence of individuals with OB (III) blood group
      and having phenotypic B8 antigen of HLA-system.

PMID- 12520906
TI  - [Cytogenetic and cellular-molecular changes under exposure to some occupational
      factors (review of the literature)].

PMID- 12520907
TI  - [Activities of the regional occupational health center under present-day
      conditions].
AB  - The authors represented experience of contemporary activities of Occupational
      center in Rostov region, demonstrated efficiency of thorough medical examinations
      carried by mobile clinical and diagnostic laboratories, suggested 4-levels
      structure of occupational service organization.

PMID- 12520908
TI  - [Use of antimicrobial articles in the prevention of pyoderma and dermatomycoses].
AB  - The authors present results of experimental and clinical studies of antimicrobial
      articles (underwear, socks, insoles and gloves) containing catamine AB and base
      use of these articles for prevention of pyoderma and dermatomycoses.

PMID- 12520909
TI  - [Diagnosis of acetylation phenotype in the protection of production personnel].
AB  - The authors elaborated noninvasive method to diagnose acetylation phenotype
      through photocolorimetric studying kinetics of sulfadimesine urinary excretion.
      Suggestion is approach to people protection through selection of inductors which
      purposefully increase individual activity of N-acetyltransferase.

PMID- 12520910
TI  - [Gas chromatography in detection of sodium formate in the ambient air].

PMID- 12520911
TI  - [Studies of biological activity of mineral oil dialkyl disulfide (an experimental
      study)].

PMID- 12520912
TI  - [Physiologic evaluation of students' resistance to examination stress].

PMID- 12520913
TI  - [Study on the relationship between cadmium immunotoxicity and corticotropin
      releasing factor].
AB  - To explore the relationship between cadmium immunotoxicity and corticotropin
      releasing factor(CRF), murine T- and B-lymphocytes mitogen-induced proliferation
      function(3H-TdR incorporation method) and CRF levels of hypothalami and blood
      plasma were observed both in cadmium chloride(CdCl2) and CdCl2 + alpha-hCRF
      treated animals in vivo. In cadmium-treated animals, T and B lymphocytes
      stimulation indexes were significantly lower than those in control(P < 0.05) with
      a dose dependent response. And interestingly, the central CRF levels in CdCl2
      treated groups were significantly higher than those in control (P < 0.05), an
      increasing CRF level was also observed accompanied by the increase of CdCl2
      level. In peripheral blood plasma, no significant difference of CRF levels was
      found among all groups(P > 0.05). When animals were treated with CdCl2 in
      combination with alpha-hCRF, no significant difference of B-lymphocyte
      proliferation function existed among the alpha-hCRF + CdCl2 groups (P > 0.05).
      Similar results were also observed in detecting T-lymphocyte proliferation
      function. Hypothalamic CRF levels among various doses of CdCl2 + alpha-hCRF
      groups showed no statistical difference, but all were higher than those in the
      control, and peripheral CRF levels had a trend to increase in alpha-hCRF + CdCl2
      co-administrated groups. The results suggested that CdCl2 showed an
      immunosuppressive action upon murine T and B lymphocytes, CdCl2 could cause
      central CRF increase. alpha-hCRF could partially reduce the cadmium
      immunotoxicity. Central CRF-mediated immunomodulation was shown in cadmium
      immunotoxical effects on murine splenic lymphocytes.

PMID- 12520915
TI  - [Effects of the expression of mouse metallothionein-I gene in human HeLa cell
      line on drug resistance].
AB  - Metallothionein-I (MT-I) gene was inserted into EcoRI site by using pSV2-neo
      plasmid vector. Recombiant plasmid was transfected into HeLa cells by DNA-calcium
      phosphate precipitation technique. MT-I expression colones were growing in medium
      including G418. The amount of MT-I expression in transfected cells was found 2.6
      times higher than that of non-transfected ones. In order to observe the
      relationship between the expression of MT-I gene in cells and drug resistance,
      cells were treated with different concentrations of cisplatin and adriamycin
      respectively. The results indicated that cisplatin (0.1 mumol/ml) inhibited the
      growth of both transfected and non-transfected cells. The inhibitory rates were
      34% and 82% respectively(P < 0.05). IC50(50% inhibitory concentration for cell
      growing) was 0.144 mumol/ml and 0.061 mumol/ml and the ratio of them was 2.36: 1
      after the treatment of cisplatin 72 h later. The cells were treated with
      adriamycin 72 h later, the inhibitory rates of transfected and non-transfected
      cells were 18% and 25% separately. The rates showed no significant difference (P
      > 0.05). The results indicated that MT was related to drug resistance of tumor
      cells.

PMID- 12520914
TI  - [MTHFR gene expression in EB virus transformed human B lymphoblasts].
AB  - In order to detect the expression of N5, N10-methylene-tetra hydrofolate
      reductase(MTHFR) gene in Epstein-Barr virus(EBV) transformed human B lymphoblast,
      as well as the cDNA sequence, human peripheral blood was transformed by EBV to
      build B lymphoblast cell line. Total RNA was isolated from the cell culture.
      Variant segments of MTHFR cDNA were amplified using RT-PCR protocol and analysed
      by polyacrylamide gel electrophoresis(PAGE). One of the cDNA segments was
      sequenced. Results showed MTHFR gene was expressed in human B lymphoblast cell
      line. The cDNA sequence was almost the same as that of human liver cDNA from
      Genbank.

PMID- 12520916
TI  - [Effects of 6 kinds of metal elements on meiotic maturation and in vitro
      fertilization on mouse oocyte].
AB  - To study the effects of Cd, Pb, Ni, Mn, Cr and Al on reproductive toxicity, the
      meiotic maturation and in vitro fertilization(IVF) of mouse oocytes were studied
      using in vitro culture and IVF of mouse oocytes. The results showed that except
      Al(NO3)2, the other groups [CdCl2, Pb(NO3)2, NiCl2, MnSO4 and CrCl3] could
      significantly reduce the number of superovulation oocyte. All of them could
      inhibit the meiotic maturation, the rates of IVF and extruding of the first polar
      body, but there was no impact on the germinal vesicle breakdown (GVBD) in vivo.
      The results also showed that except Al(NO3)3, other elements could obviously
      inhibit germinal vesicle breakdown of mouse oocytes. The results suggested that
      these elements might damage the process of meiotic maturation of oocyte of women
      at child-bearing age oocyte and reduce the fertility and reproductive capacity
      and result in sterile.

PMID- 12520917
TI  - [Study on method of sampling and analysis of acephate in the air].
AB  - Acephate in the air was collected with polyurethane foamed plastics, desorbed
      with methanl, separated with a column 2% DEGS and determined by GC-FPD. The
      detectable limit was 0.052 mg/m3. When the concentration of standard solution was
      3-15 micrograms/ml, the relative standard deviation(RSD) was 4.5%-2.3%. The
      desorption efficiency was above 85%. The sampling efficiency was 100%. The
      samples were stable for 24 h. It was proved that the method was accurate, fast
      and simple. It was suitable for the determination of acephate in the air.

PMID- 12520918
TI  - [Effects of bacterial protective liquid on radiation biology effect of mouse bone
      marrow cells].
AB  - To study the relationship between bacterial protective liquid (BPL) and the
      biological effect of mouse bone marrow cells by gamma-ray irradiation, apoptosis
      and the number of CD4+, CD8+ and NK cells were analyzed by flow cytometry(FCM),
      the results showed that BPL decreased the apoptosis and increased the
      proliferation of cells(P < 0.01). The theorem of action was related with raising
      the percentage vitality of NK cells and the quantity of CD4+ and CD8+. This study
      proved that BPL might have protective effect against radiation injury.

PMID- 12520919
TI  - [Relationship between the ultrastructural characteristic of coal dust and its
      toxicity].
AB  - To study the relationship between the ultrastructural characteristic of coal dust
      and its toxicity, we compared two types of coal dusts which damaged alveolar
      macrophages(AMs) concerning with the coal dusts ultrastructural characteristic by
      using microscopy and biochemical techniques. The results showed that coal dusts
      damaged not only AMs plasma and lysosomal enzymes but also in ultrastructure. The
      coal dust in Nanpiao mine had a sharp form, fragile texture and a structure
      putting in order. It was concluded that: (1) the toxicity of coal dust in Nanpiao
      mine was higher than in Kailuan mine and which was related to the ultrastructural
      feature of the coal dusts; (2) the AMs injury degree by coal dusts was more and
      more serious with the duration of exposure to coal dusts.

PMID- 12520920
TI  - [Electric maze test in rats after prenatal methylmercury exposure].
AB  - To study the changes of rat's learning and memory ability in maze test after
      prenatal methylmercury exposure, methylmercury in doses of 0, 0.01, 0.05 and 2.00
      mg/(kg.d) were fed to pregnant rats at the 6th-9th day after conception. We
      adopted a Y-shaped electric maze to detect learning and memory ability of the rat
      offspring. Double blind was used in the experiment. The results showed that the
      error times and arrival time of all exposure groups were more, and active
      avoidance ratio of all exposure groups was less than that of control group. The
      differences were significant(P < 0.05 or P < 0.01). There was no difference
      between male and female rats. It is concluded that methylmercury could affect the
      growth and development of central nerve system. The learning and memory ability
      of rat offspring was greatly damaged.

PMID- 12520921
TI  - [Value of combined detection of tumor markers for the prediction of small cell
      and non-small cell lung cancer].
AB  - To evaluate the value of detection of 4 tumor markers(CEA, CA125, gastrin, and
      NSE) for histological types in patients with lung cancer and to improve the
      predicted efficiency of tumor markers for distinguishing between small cell lung
      cancer(SCLC) and non-small cell lung cancer (NSCLC), these 4 tumor markers in
      serum were determined in 51 patients (21 cases with SCLC, 30 cases with NSCLC)
      with confirmed primary diagnosis of lung cancer of different histology by
      radioimmunoassay. Linear learning machine method, PRIMA method and KNN method
      were used to classify SCLC and NSCLC. The levels of gastrin and NSE in SCLC were
      apparently higher than those of gastrin and NSE in NSCLC, but the levels of CEA
      and CA125 in SCLC were significantly lower than those in NSCLC. Smoking had an
      effect on the levels of CEA and CA125, but had little effect on those of gastrin
      and NSE. The total accuracy of the three methods was over 85% in distinguishing
      SCLC from NSCLC. So combined detection of the four tumor markers in serum might
      be useful in the prediction of histological types in patients with lung cancer.

PMID- 12520922
TI  - [Effects of selenium and zinc on the DNA damage caused by fluoride in pallium
      neural cells of rats].
AB  - To investigate the effects of fluoride on DNA damage as well as the effects of
      selenium and zinc against fluoride respectively or jointly in pallium neural
      cells of rats, single cell gel electrophoresis was used to detect the DNA damage
      of neural cells prepared in vitro. The results showed that the degree of DNA
      damage in the fluoride group and the selenium group were significantly greater
      than that in control group(P < 0.01). The damage in the fluoride group was even
      more serious. The damage in the fluoride + selenium group and fluoride + zinc
      group was slighter than that in the fluoride group but with no significant
      difference. The extent of DNA damage in the fluoride + selenium + zinc group was
      significantly slighter than that in the fluoride group(P < 0.05). It suggested
      that fluoride and selenium could induce DNA damage in pallium neural cells of
      rats respectively. Moreover, the joint antagonistic effect of selenium and zinc
      against fluoride was more obvious.

PMID- 12520923
TI  - [Survey on children's dental fluorosis and fluoride content in urine after
      defluridation to improve drinking water].
AB  - The authors surveyed the dental fluorosis and fluoride content in urine of 8-12
      years old children's in 1993 to 1999 for the evaluation of the efficiency to
      prevent endemic fluorosis after defluoridation to change drinking water source in
      Guangdong Province. Three villages: slight fluorosis area in Dazhai village,
      middle fluorosis area in Hupi village and severe fluorosis area in Anquan village
      in Fengshun County were surveyed. The results showed that the fluoride contents
      in drinking water were 1 mg/L (or less) in Anquan village, at the same time the
      prevalence of dental fluorosis and indexes of dental fluorosis were decreasing as
      changing water time. Fluoride contents in urine were normal. But in other two
      villages, the fluoride contents in drinking water exceeded 1 mg/L, therefore the
      children's prevalence rates and indexes of dental fluorosis were higher than the
      national standards. It is important to keep fluoride contents in drinking water
      under 1 mg/L for preventing endemic fluorosis by defluoridation to improve
      drinking water.

PMID- 12520924
TI  - [Analysis on skin allergy of rural residents in Anqing area].
AB  - To investigate the allergy reaction of rural residents against 12 categories
      sensibiligen, 9,232 sensibiligen peasants from rural areas of Anqing were
      observed by 12 categories sensibiligen in skin(methods: point thron). If the
      diameter of papule erygthema was bigger than that of histamines of control, the
      reaction was considered to be positive. All cata was analyzed by sas software.
      The results showed that the allergy reaction degrees were different among the
      groups with different genders and ages. Family susceptibility was noticed.

PMID- 12520925
TI  - [Effects of silk hydrates on the blood glucose metabolism in rats with
      experimental diabetes].
AB  - Male Wistar rats were divided into two groups by random. One group was injected
      with streptozotocin(STZ) 30 mg/kg BW via tail vein. Three weeks later, the rats
      were fed on diet of high fat, high sucrose and high calorie for another 8 weeks.
      There were 38 rats with impaired glucose tolerance and insulin level higher or
      equal to the control group selected as the diabetic model group. Another 36 rats
      not injected with STZ and fed on normal diet were selected as controls. The two
      groups were divided into two subgroups and fed with normal diet for another 4
      weeks. The four subgroups were normal control group, normal +SH group, diabetes
      control group and diabetes +SH group. The rats in normal +SH group and diabetes
      +SH group were tube feeding every day with silk hydrate (SH) 1.0 g/kg BW for 4
      weeks. The results showed that in the diabetes +SH group, the glucose tolerance,
      blood lipid and the predictive index of coronary heart disease were significantly
      improved, but no effect on their blood insulin level. There was no change in the
      normal +SH group. The results suggested that SH could modulate the metabolism of
      blood glucose and partly improve the disorder of the serum lipid of diabetic
      rats.

PMID- 12520926
TI  - [Effects of vitamin E and vitamin C on nonenzymatic glycation and peroxidation in
      experimental diabetic rats].
AB  - SD rats were peritoneally injected with streptozotocin (STZ) to establish
      diabetic animal model. The changes of nonenzymatic glycation and peroxidation in
      rats supplemented with vitamin C and/or vitamin E during five weeks were
      investigated. It was found that the glycated hemoglobin, glycated LDL, renal
      cortical AGEs and MDA in sera and renal cortex significantly decreased after
      supplementation of vitamins E and C jointly. It was also observed that the MDA in
      serum and the cortex of kidney but not glycated hemoglobin, glycated LDL and AGEs
      significantly decreased in the groups supplemented with vitamin C or vitamin E
      separately. The results suggested that joint supplementation of vitamin C and
      vitamin E could inhibit nonenzymatic glycation obviously and peroxidation in
      diabetic rats and protect the kidney from damage under hyperglycemia.

PMID- 12520927
TI  - [Effects of alpha-tocopherol and beta-carotene on the oxidized low density
      lipoprotein induced by Cu2+].
AB  - The effects of different concentrations of alpha-tocopherol and beta-carotene on
      low density lipoprotein(LDL) oxidation were examined. LDL was oxidized by Cu2+ in
      a cell-free(10 mumol/L Cu2+ in PBS) system. The results showed that alpha
      tocopherol and beta-carotene inhibited the oxidative modification of LDL in this
      system as evidenced by a concentration-dependent decrease in lipid
      peroxide(thiobarbituric-acid-reasting substances activity, TBARS) and the
      electrophoretic mobility of LDL. The effect of alpha-tocopherol on the generation
      of TBARS was stronger, while on the electrophoretic mobility was weaker than that
      of beta-carotene. Both alpha-tocopherol and beta-carotene slightly but not
      significantly reduced lipofusin. It suggested that the mechanisms were different.
      Thus, beta-carotene, as well as alpha-tocopherol, inhibit LDL oxidation and might
      play important roles in reducing the generation of oxidized LDL.

PMID- 12520928
TI  - [Study on the chemical form and extraction rate of Cr, Cu, Fe, Mn, Ni and Zn in
      tea].
AB  - The content of Cr, Cu, Fe, Mn, Ni and Zn in the tea commonly available in China
      market were measured by inductivity coupled plasma-optical emission spectrometry
      (ICP-OES). The extraction rates of the six elements in tea leachate were
      measured. The solubilitied were 39.8% for Cr, 42.5% for Cu, 8.6% for Fe, 45.5%
      for Mn, 87.1% for Ni and 71.0% for Zn. The process of making tea leachate affects
      the elements extraction rates. The content of the microelements in tea leave
      extracts decreases gradually with the processing. About 80% of Cr, Cu, Mn, Ni and
      Zn and 60% of Fe were in the first infusion of tea. Moreover, the chemical forms
      of six elements were determined. The ratios of organic to inorganic forms were
      0.33 for Cr, 0.022 for Cu, 0.18 for Fe, 0.002 for Mn, 0.01 for Ni and 0.18 for
      Zn. It is concluded that the six elements from the tea infusion extracted from 5
      g tea are too little to meet the recommend dietary allowance (RDA). Therefore,
      tea is not a rich food source of Cr, Cu, Fe, Mn, Ni and Zn.

PMID- 12520929
TI  - [Study on vitamin E succinate inducing apoptosis of human gastric carcinoma
      cell].
AB  - The effects of vitamin E succinate (VES) on the growth of human gastric carcinoma
      SGC-7901 cell were observed in cell culture. The apoptosis of SGC-7901 cell
      induced by VES was studied by fluorescent staining and flow-cytometry. The
      results showed that VES (5, 10 and 20 mg/L) could obviously inhibit the growth of
      gastric carcinoma cell, and it could be the result of inducing apoptosis.

PMID- 12520930
TI  - [Protection of beta-carotene and vitamin C on the transformation of human lung
      fibroblasts cell induced by nickel sesquioxide].
AB  - In order to study the protection of beta-carotene and vitamin C against the
      transformation of human lung fibroblasts (HLF) cell induced by nickel
      sesquioxide, HLF cells were treated repeatedly by different concentrations of
      Ni2O3 in vitro. beta-carotene (5.4 mg/L) and vitamin C(1.8 mg/L) were added into
      the media containing Ni2O3(1.0 mg/L) respectively. The identification of
      malignancy of the transformation of HLF cell was carried out by the tests of ConA
      and the growth on semisolid agar culture. The results showed that Ni2O3 could
      induce the malignant transformation of HLF cell. The transformed cell
      proliferated rapidly. The transformed colonies exhibited in extensively random
      orientation and the cells were crossingover. The frequency of transformation
      showed a dose-response relation at the experimental concentrations. The
      transformed cell could be agglutinated by lower concentration of ConA and could
      grow in semisolid agar. The frequencies of transformation of HLF cell exposed to
      beta-carotene and vitamin C were decreased significantly. The cells could not be
      agglutinated by ConA and not grow in semisolid agar. It was concluded that Ni2O3
      could induce strongly the malignant transformation of HLF cell and might be
      carcinogenic to human. The protection of beta-carotene and vitamin C on the
      transformation of HLF cell induced by Ni2O3 was observed. The increase of foods
      riched in beta-carotene and vitamin C was suggested for workers exposed to
      nickel.

PMID- 12520931
TI  - [Regulation effect of curcumin on blood lipids and antioxidation in
      hyperlipidemia rats].
AB  - The regulation effects of curcumin on lowering blood lipids and antioxidation
      were studied in the hyperlipoidemia model Wistar rats fed with high fat diet for
      4 weeks. The hyperlipoidemia model rats were then separated into four groups:
      normal diet group, normal diet + curcumin (5 g/kg) group, high-fat diet group and
      high-fat diet + curcumin group. The rats were fed with experimental diets for
      another 4 weeks respectively. The results indicated that curcumin decreased the
      serum levels of cholesterol and triglyceride and increased the serum level of
      apolipoprotein A. Curcumin decreased TBA value and improved total antioxidation
      capability. The activities of SOD and GSH-PX in liver were enhanced. After taking
      normal diet for four weeks, the blood fat and cholesterol levels of the
      hyperlipoidemia rats recovered. But in the normal diet + curcumin group, the same
      results could be found in two weeks.

PMID- 12520932
TI  - [Determination of guanine plus cytosine content of Pseudomonas cocovenenans subsp
      farinofermantans with two methods and the comparative study].
AB  - The guanine plus cytosine content (G + C) mol% of Pseudomonas cocovenenans subsp
      farinofermantans, Burkholderia gladioli and Burkholderia cocovenenans, which were
      similar in biochemical characteristics, were determined with Tm values method and
      HPLC method, and the comparative study of these two methods was discussed. A
      negative conclusion could not be made from the results. The three bacteria were
      the same species. The HPLC method was more accurate than the Tm values method,
      but the repeatability of the latter was better.

PMID- 12520933
TI  - [Identification of Listeria species in 167 kinds of foods].
AB  - Through preliminary identification of isolation of Listeria species in six types
      foods, which consisted of 167 kinds of foods, we found both S-form and R-form
      colonies were suspected colonies of Listeria species, and some of them were
      catalase-negative, urease-positive, methyl red(MR) negative and Voges
      Proskauer(VP) negative. The results showed that S-form, catalase-positive, urease
      negative, MR-positive and VP-positive colony should not be used as the strict
      criteria for the identification of Listeria.

PMID- 12520934
TI  - [Study on the effect of several antioxidants on the stability of oils].
AB  - The stability of oils is very important for ensuring the sanitation and quality
      of oils and the foods containing oils and fats. In this study, BHT, TBHQ and
      micro-capsule antioxidants (mixed antioxidants) were tested for their properties
      of antioxidation in oils under different temperatures. The results showed that
      the mixed antioxidant used in oils was more effective than the single
      antioxidant, especially under high temperature. It was concluded that
      microcapsule antioxidant was effective, economical and relatively safe when it
      was used in oils for frying foods.

PMID- 12520935
TI  - [Indicators for the assessment of iodine nutritional status].
AB  - Selecting appropriate evaluation indicators for surveying and monitoring iodine
      nutritional status is needed. The indicators, which are used commonly in recent
      literature, are urinary iodine, thyroid volume, dietary iodine intake, thyroid
      function parameters and intelligence quotient. These indicators are summarized on
      their clinical significance, application range, expression method and so on. The
      purpose of this review is to provide some scientific references for people who
      are working on prevention and treatment of iodine deficiency disorders.

PMID- 12520936
TI  - [Domoic acid and glutamate receptors].
AB  - Domoic acid is a kind of neurotoxin produced by diatoms and accumulated in food
      chain, which is harmful to the human health. The N-methyl-D-aspartate receptor
      and kainic acid/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor
      could be activated by domoic acid. The concentration of the intracellular Ca2+
      could be elevated, causing a series of physiological and biochemical changes. The
      possible mechanisms of neurotoxicity induced by domoic acid through glutamate
      receptors are discussed.

PMID- 12520937
TI  - [General report on food and nutrition surveillance in 1998 and policy
      recommendation].
AB  - Based on the data of collection, nutrition status of children, food consumption
      and nutrition of urban and rural residents are analyzed, and related policy
      recommendations are presented. The improvement of the nutritional status of
      children in China is the consequence of socioeconomic development. The strategy
      for child nutrition improvement should focus on rural area and complementary
      feeding should be a key approach as important as breastfeeding to be stressed on.
      Immediate set priority on approaches promoting consumption production and
      processing of soybean. Nutrition problem of the poor should and could be resolved
      to consolidate the achievement of the National Poverty Alleviation Program.

PMID- 12520938
TI  - [Protocol and quality control for Chinese food and nutrition surveillance system
      in 1998 (1998 CFNSS)].
AB  - Establishment of Chinese Food and Nutrition Surveillance System is of great
      importance in providing information on food consumption behavior and nutrition
      status of the people which is essential for health, economic planning and
      agriculture development. Sampling of CFNSS is based on the 145 sites Disease
      Surveillance Point (DSP) System built by Ministry of Health, and in conjunction
      with the 600 sites Household Social Economic Survey System founded by State
      Statistics Bureau. According to indicator system developed by the Ministry of
      Health for stratification, strata of urban, general rural and less-developed
      rural were defined and 40 sites were randomly sampled as national sample. The
      CFNSS sample was the common sub-sample of DSP system and the SSB Household Survey
      System that makes sharing of information resources possible. The 40 sites are
      distributed in 26 Provinces/Municipalities/Autonomous Regions. All the sites
      information was collected on body weight and height of children under 6 years of
      age, and questionnaire covering the basic family information, feeding practice
      and disease, health conditions of the households were surveyed by interviews.
      Whole year food consumption data collected at the sampled households by SSB Urban
      Household Survey Team and Rural Household Survey Team in the previous year was
      provided. Comprehensive data analysis was done to formulate the information on
      the relationship of food, nutrition and health. The protocol, methodologies and
      principles for the survey are described. 5 sites of CFNSS were selected for
      quality evaluation on the anthropometric measurement and questionnaire interview.
      The body weight and length of 20 children of 3-5 years of age in each of 5 sites
      was measured again. The result showed that the completeness of questionnaires
      interview was 96%, the rate of logic error was zero. There was no significant
      difference between the results measured by supervisor and investigator and no
      significant error on repeated measurements. The reliability of data R = 0.95. The
      results showed that the data was accurate and reliable.

PMID- 12520939
TI  - [Protocol for sampling of Chinese food and nutrition surveillance system
      (CFNSS)].
AB  - Based on the 145-site Disease Surveillance Point System (DSP) of the Ministry of
      Health in conjunction with 600-site Urban/Rural Household Socio-economic Survey
      System of State Statistic Bureau carried out by the Urban Household Socio
      Economic Survey Team and Rural Household Socio-Economic Survey Team. Three strata
      including urban, general rural and less-developed rural were defined. Sample size
      of 16,000 children was designed according to the estimate of 5% underweight
      prevalence of children under 6 years of age. 40 sites were sampled by stratified
      random sampling, involving 14 urban sites, 17 general rural sites and 9 poor
      rural sites in 26 provinces. The total population of the 40 sites is 20.678
      million, which is 1.7% of whole population of the country. 400 children under 6
      years of age were sampled by Multi-stage Cluster Sampling at each site. The
      consistency of age distribution of children between the sample and the National
      Population Census data in 1990 by Goodness of Fit Test indicated the
      representativeness of the sample is reliable.

PMID- 12520940
TI  - [Current situation and trend of child growth in China].
AB  - Data of Food and Nutrition Surveillance in 1990, 1995 and 1998 was analyzed; it
      indicated the evident improvement of weight and height of children under 5 in the
      past eight years. The prevalence of underweight were reduced from 8.0% in 1990 to
      2.7% in 1998 in the urban, and in the rural, the prevalence were 22.0% and 12.6%
      respectively. The reduction of prevalence of stunting in the urban decreased from
      9.4% to 4.1%, and in the rural from 41.4% to 22.0% in the same period. During
      1990-1995, weight of children under 5 went up evidently, but linear growth
      improvement was very slow and did not match the weigh gain. Height of children
      increased in a higher speed during 1995-1998. Height and weigh of age groups
      indicated that 6-18 month was the critical period for prevention of malnutrition
      of children under 5. The paper further analyzed the favorable changes of the
      attributable factors of malnutrition, such as diarrhea, safe drinking water,
      breastfeeding, education level of mothers, household diet and income during this
      period. The conclusion is the remarkable nutrition improvement of children under
      5 in 1990s is the consequence of the rapid socio-economic development of China.

PMID- 12520941
TI  - [Exclusive breastfeeding and growth of infants under 4 months in China].
AB  - Data collected at the 40 CFNSS sites in 1998 was analyzed on the relationship of
      exclusive breastfeeding and the growth, diseases of infant aged under 4 months.
      The results showed that the exclusive breastfeeding rates (EBF) of children under
      4 months were 53.7% in urban and 76.6% in general rural, but was 64.6% in the
      poor rural. EBF rate of the stunted children was 57.3% that was significantly
      lower than the infants with normal length. 73.0%. The infants EBF under 4 months
      were 0.36 kg heavier, 1.2 cm longer, and WAZ 0.4 and HAZ 1.53 higher than the non
      EBF infants. Prevalence of diarrhea were 13.1% among EBF and 29% in non-EBF
      infants. Logistic regression analysis showed that odds ratio (OR) of stunting for
      non-EBF infants was 2.19, OR of diarrhea was 2.74.

PMID- 12520942
TI  - [Relationship between growth of young children and complementary feeding].
AB  - Description analysis, correlation regression analysis and logistic regression
      analysis were applied to evaluate the impact of complementary food on the growth
      of children from the aged 4 to 24 months, results on the effect of the
      complementary feeding were presented. Among children under 2 years in poor rural
      areas, 42% of them got complementary food containing animal food, 30.5% got milk,
      57.8% got starchy foods, and 48.6% got vegetables and fruits. The coverage of
      complementary food containing animal food, vegetables/fruits was only half of
      that in the urban areas. Analysis revealed significantly positive correlation of
      HAZ, WAZ of all age group of children under 2 years with the appearance of animal
      foods, vegetable and fruit in the complementary food, but there was no
      significantly correlation with starchy foods. According to the regression
      coefficient, it was estimated that the prevalence of stunting aged 18-24 months
      could be reduced 2.6 percentage points if 10% increase of coverage of animal food
      containing complementary food in the CFNSS site was achieved. Logistic regression
      analysis showed the odds ratio (OR) of non-animal food complementary food for
      stunting was 2.21 for children aged 4-6 months, 1.73 for 6-12 months, 2.81 for 12
      18 months, 2.58 for 18-24 months, OR for underweight was 2.87 for 12-18 months,
      and 2.08 for 18-24 months.

PMID- 12520943
TI  - [Status and economic losses of respiratory infection and diarrhea of children
      under 6 years].
AB  - Based on the data collected from the CFNSS in 1998, the status and trends of
      respiratory infection and diarrhea of children and the economic losses caused by
      the two diseases were analyzed. The prevalence of two-week respiratory infection
      of urban children under 6 was 23.75% and 21.97% in the general rural, and 26.03%
      in poor rural. The peak of respiratory infection of rural children was at 6-18
      months, but in the urban, that was at age of 3-4 years. Before 2 year of age, the
      respiratory infection was higher in the rural, and after that age it was higher
      in the urban. Since 1990, the prevalence of respiratory infection went up and
      increased 9.5 percentage points over 8 years in the urban, the percentage point
      of increase was 6.9 in the rural during the same period. In 1998, the prevalence
      of diarrhea of rural children under 6 was 7.0%, higher than in the urban, which
      was 4.3%. The prevalence reduced from 9.4% to 4.3% during 1990-1998 in the urban,
      and in the rural from 13.0% to 7.0%. Weight and height of children with diarrhea
      incidence were significantly lower than children without diarrhea. Calculation
      based on the cost for the episodes of the two diseases and the disease prevalence
      was made and estimate of the economic losses was 11,793 yuan (RMB) for urban,
      5458 yuan (RMB) for rural areas.

PMID- 12520944
TI  - [Food consumption and dietary pattern in China during 1990-1998].
AB  - Based on data of food consumption collected in the household survey of State
      Statistics Bureau in 1990 and 1995, consumption of soybeans and its production
      decreased in all household. Urban population over-consumed animal food, intake of
      cereals reduced and energy share of cereals was dropped to less than 60%. Rural
      population consumed mainly cereals, animal food, fruit and oil consumption was
      lower. 1998 data showed that the animal food consumption increased along with
      income increase, but vegetable oil consumption kept stable. Dietary pattern of
      urban household were still relatively rational, but animal food consumption still
      needed to be increase in the rural households, and more attention should be paid
      to the poor households. Enhancement of nutrition education and promotion of
      soybean consumption and production for nutrition improvement for both urban and
      rural population was recommended to make urban diet to meet the goals of a
      balanced diet and the rural diet to be nutritionally adequate.

PMID- 12520945
TI  - [Assessment of dietary pattern in China with desirable dietary pattern].
AB  - Applying desirable dietary pattern (DDP) to analyze the quality of the diet in
      urban and rural household in 1995 and 1998 was presented. The results showed
      that: urban people should adjust the structure of their diet, to level down the
      increasing trend of animal food, as a replacement, more soybean consumption
      should be encouraged. Rural people should increase moderate amount of animal food
      and oils, and increase of vegetable/fruits and overall non-staple foods could
      keep the diet quantitatively and qualitatively improved and balanced. Promotion
      of soybean consumption in the rural households was the most feasible and
      effective way of improving nutritional quality of the diet in the rural in the
      near future.

PMID- 12520946
TI  - [Sampling survey for iodine content of iodized salt in household of CFNSS in
      1998].
AB  - The sampling survey for iodine content of iodized salt was conducted in 36 food
      and nutrition surveillance sites of CFNSS in 1998 in China, which covered 26
      provinces, 362 portions of salt samples. The average compliance rate was 76.0%,
      83.2% in Urban area and 71.9% in Rural. Iodine content of salt less then 20 mg/kg
      at the rural households was 20.4%, and 9.9% in urban.

PMID- 12520947
TI  - [Preliminary analysis of the hemoglobin levels of children under 6 years of age].
AB  - Among the 40 survey sites in the "China Food and Nutrition Surveillance Project",
      we picked six sites to estimate the Levels of preschool children and collected
      2416 valid cases. Our analysis formed the following results: Children anemia
      prevalence level was 16.8%, which was higher than the figure from the "Third
      National Nutrition Survey in 1992", and was lower than that from the Nutrition
      Surveillance and Improvement Project in 101 poor countries". The situation where
      the anemia prevalence was above 20% existed not only in poor rural villages, but
      also in other rural areas in general as well as cities. Looking at different age
      structures, we found that the anemia prevalence level was the highest for
      children aged six to twelve months. The number was as high as 30.90%, consistent
      with results from many earlier research projects.

PMID- 12520948
TI  - [Reporting system of Chinese food and nutrition surveillance in 1998].
AB  - The software of reporting system for Chinese food and nutrition surveillance in
      1998 is the key part of China Food and Nutrition Surveillance System (CFNSS) in
      1998. By means of modern information technology to process the contents of
      questionnaires of CFNSS, and using professional software to conduct data
      analysis, useful information has been created. The software consists of 4
      modules: data entry program for CFNSS, anthropometric calculation, data analysis
      and data transmission. It is also an open system, the users can use the tool
      offered by the system to conduct further analysis based on their own situation,
      and even developing a surveillance system.

PMID- 12520949
TI  - [Nutrition and economic development of poor areas].
AB  - The relationship between nutrition and economic development is discussed, it
      illustrates that nutrition is not only the consequence of economic development,
      but also as one of the motive power, playing important role in economic
      development. The authors reviewed the scientific insight of the impact of
      malnutrition on disease prevalence, mental development, adult physical capability
      and productivity. Data on nutrition status of population in the poor areas and
      the analysis on the risk of chronic disease poverty population facing to are
      presented. In order to protect the health of the poor, and to guarantee the
      physical efficiency and productivity of the current labor force in poor areas,
      and to provide a mentally and physically well developed manpower for the future
      economy, the authors appeal to the policy-makers to integrate nutrition component
      into poverty alleviation program. Several low cost and effective approaches for
      nutrition improvement are listed.

PMID- 12520950
TI  - [Effect of exposure to low concentration of benzene and its analogues on luteal
      function of female workers].
AB  - The effect of benzene and its analogues(BIA) on the luteal function of female
      workers was studied in a petrochemical corporation. The female workers from a
      chemical fiber corporation without benzene exposure were selected as controls.
      The levels of BIA(toluene and xylene) in the air at breathing zone were sampled
      and determined with gas chromatography(GC). The menstrual function was followed
      up. Urine pregnanediol-3-glucuronide (PdG) and follicular stimulating
      hormone(FSH) were measured by enzyme immunoassay(EIA). The results showed that
      BIA existed in low concentration in air. The exposure could lead to a shorter
      length of time of luteal phase(P < 0.05 or P < 0.01) and decrease luteal
      progesterone level (P < 0.05). It was suggested that the low concentration of BIA
      exposure could have effect on the luteal function in exposed female workers, and
      urinary hormones could be used as biomarker for the influences of benzene and BIA
      on reproduction.

PMID- 12520951
TI  - [Effect of sub-acute low level exposure to lead on cellular immune function in
      rats].
AB  - In order to observe the influence of low level exposure to lead on cellular
      immune functions in rats, sixty rats were randomly divided into six groups and
      were received diets with different levels of lead for eight weeks. Blood lead,
      serum tumor necrosis factor-alpha(TNF-alpha) level and the distribution of T
      lymphocyte subsets were measured. The pathological and ultrastructural changes of
      spleen were investigated. It was shown that lead exposure resulted in a
      significant increase of blood lead and decrease of the number of CD4 T-cells. But
      no significant difference was found in CD8 T-cell among all groups. Serum TNF
      alpha at the lowest exposure group was significantly increased but that in other
      groups was lower than the control group. Electron microscopy for splenic immune
      cells indicated no significant difference between the lowest lead exposure group
      and the control group. The mitochondria of other groups were swollen, vaculated
      and pyknotic, endoplasmic reticulum were swollen and degranulated, nuclear
      chromatin were loosen. It was suggested that sub-acute exposure to lead, even at
      relative low exposure, would impair cell-mediated immunity and be harmful to
      spleen and thymus.

PMID- 12520952
TI  - [Application of indigo disulphonate spectrophotometry on the determination of
      ozone in indoor air].
AB  - Spectrophotometric determination of ozone in indoor air by using indigo
      disulphonate was investigated. The results showed that the average recovery of
      ozone was 99% and the relative standard deviation was 2.3% when the concentration
      of indoor ozone was in the range of 0.2-1.0 microgram/ml. The lowest detection
      concentration was 0.009 mg/m3 (sampling 20 L) when the range of determination was
      0.18-10.0 mg/10 ml.

PMID- 12520953
TI  - [Study on multi-element determination in drinking water by ICP-OES and ICP-MS].
AB  - A new method was developed for the determination of twenty-three elements in
      water samples by ICP-OES and ICP-MS. The detection limits, standard deviations
      and linear calibration ranges were measured. The sensitivity of the method was
      excellent and the determination was very fast for various elements including Ca,
      Mg, Fe, Mn, B, Cr, Si, Zn, Be, Al, V, Co, Ni, Cu, As, Se, Mo, Ag, Cd, Sb, Ba, Tl
      and Pb. Preconcentration and separation procedures were not required and hence
      the potential cross contamination was minimized. Recoveries of the standards
      spiked to natural samples were at the range of 94.5%-116.2%. Besides, the
      analytical values of standard reference materials obtained by the proposed method
      were conformed well with the certified values. The accuracy of results was
      further validated by comparing with the data obtained by using AAS and AFS. The
      proposed method was applied in the quality study of Shenzhen drinking water. A
      precise and accurate background data of various trace elements content of the
      city was obtained.

PMID- 12520954
TI  - [Relationship between blood lead and free erythrocyte-protoporphyrin of female
      workers exposed to low concentration of lead operating environment].
AB  - The thesis focused in the research on whether low-lead operation would have
      effects on female workers. Based on investigation of 82 female workers under an
      operation environment with lead concentration of 0.0315 mg/m3, the following
      report indicated that differences did exist in terms of free erythrocyte
      protoporphyrin(FEP), lead-blood(Pb-B) and lead-urine(Pb-U) values between the
      exposure and control groups. Pb-B, FEP and Pb-U were found closely interrelated
      and comparatively sensitive. Dose-response relationship was discovered in the
      process, positive percentage of Pb-B and FEP were 20.73% and 21.95% respectively,
      13.4% above the maximal standard in both cases. In consequence, it was concluded
      that exposure to the 0.0315 mg/m3 lead concentration (0.03 mg/m3 being the
      normal) was still harmful to the female workers. Apart from that, the article
      suggested that the upper limit of lead in blood for common women (in Changchun
      city) was properly defined at 1.46 mumol/L. With FEP as the standard, the article
      made repective comparisons on the female workers' intelligence quotient (IQ) and
      the symptom occurrence of the neural system. People with IQ value between 60 to
      79, 80 to 89, 90 to 109 or 110 to 119, the rates of showing positive report with
      FEP > or = 0.90 mumol/L were 27.6%, 22.6% and 15.0% respectively. The general
      occurrence rate on various level of FEP was obviously higher than that of the
      control group. The highest occurrence rate of 208.32% and 58.74% appeared when
      the FEP value was between 0.36 mumol/L to 0.54 mumol/L. When we made the
      comparison according to different symptoms as headache, dizziness, hypomnesis,
      somnipathy, palpitation and ephidrosis, the occurrence rate of headache was
      distinctively highger than that of the somnipathy.

PMID- 12520955
TI  - [Effects of cadmium on the expression of proto-oncogene c-fos and c-jun of liver
      cell in rats].
AB  - The effects of cadmium chloride on the expression of proto-oncogene c-fos and c
      jun of rat liver cells were studied with Northern dot hybridization. The results
      showed that at the dose of 5, 10 or 20 mumol/kg of cadmium chloride, the
      expression of proto-oncogene c-fos and c-jun could be induced obviously.

PMID- 12520956
TI  - [Effects of electromagnetic radiation from cellular telephone handsets on
      symptoms of neurasthenia].
AB  - In order to study the effects of electromagnetic radiation from cellular
      telephone handsets on symptoms of neurasthenia, 115 and 101 persons with or
      without handsets were selected. The subjects were investigated by questionnaire
      on their general health, lifestyle, habit, mental stress, the frequency of using
      the handsets, living and working environment, the cases of suffered from diseases
      and symptoms of neurasthenia. The data were analyzed by Chi-square test and
      Logistic regression statistics. The results showed that the time of using handset
      was positively associated with depression (P < 0.05), nausea (P < 0.01) and loss
      of appetite(P < 0.05). The results showed that long time use of cellular
      telephone handset could induce the symptoms of neurasthenia.

PMID- 12520957
TI  - [Simultaneous determination of fluoroacetamide and tetramethylendisulfotetramin
      with gas chromatography-mass spectrography].
AB  - Simultaneous determination of fluoroacetamide and tetramethylendisulfotetramin
      with gas chromatography-mass spectrography was established. The condition of
      separation, ways of extraction, the qualitative and quantitative determination of
      two compounds were discussed. The linear ranges of fluoroacetamide and
      tetramethylendisulfotetramin were 5-40 micrograms/ml and 0.5-20.0 micrograms/ml,
      respectively. The recoveries of these two compounds in different sample were
      52.25%-94.30% and 61.85%-92.50%, respectively. The method was fast, sensitive and
      accurate.

PMID- 12520958
TI  - [Effect of chromium gluconate on body weight, serum leptin and insulin in rats].
AB  - In order to observe the effect of chromium on rat body weight, serum leptin and
      insulin, eight groups of rats were randomly fed diets (basal diet or high-fat
      diet) with different levels of chromium gluconate [proximally Cr(III) 1,2 and 3
      mg/kg BW]. All rats were weighted once a week. By the end of the 8th week, all
      rats were decapitalized and the levels of serum leptin and insulin were tested by
      RIA method. The ratio of liver, spleen, kidney and testickle to body weight were
      calculated. The average body weight and the levels of leptin and insulin of high
      fat-diet groups were significantly higher than those of the basal-diet group (P <
      0.05), but the insulin and leptin of groups with chromium were significantly
      lower than their corresponding control groups without chromium(P < 0.05). It was
      concluded that chromium could cause weight loss slightly and reduce the levels of
      insulin and leptin.

PMID- 12520959
TI  - [Cloning of mouse endostatin and primary analysis on its biological activity].
AB  - The mouse endostatin cDNA was cloned by the total RNA of Chinese Kunming mouse
      liver as template with RT-PCR. The results of sequencing showed one base pair
      difference. The ctg was replaced by gtg(L22545 in GenBank) at position 278 base
      pair, causing the encoded amino acid from reported Val to Leu in this experiment.
      This new endostatin cDNA was registered in GenBank with an accession number of
      AF257775. The recombinant eukaryotic expression plasmid pSecTag2-ES was then
      constructed and transfected into COS-7 cells for transient expression. The
      results of testing by Western blotting showed an expression fragment in
      supernatants of pSecTag2-ES transfected COS-7 cells at 48 and 72 hours of
      transfection. Cultured HUVECs were used to detect the biological effect of
      supernatants in pSecTag2-ES transfected COS-7 after 48 hours of transfection. 3H
      incorporation assay showed an obvious inhibition of endothelial cell
      prolifetation. The results demonstrated primary that the cloned endostatin cDNA
      had biological activity.

PMID- 12520961
TI  - [Mechanism of silk hydrates on modulating the blood glucose metabolism in rats
      with experimental diabetes].
AB  - Thirty eight adult male Wistar rats injected with streptozotocin(STZ) 30 mg/kg BW
      via tail vein and fed on a diet of high fat, high sucrose and high calorie for 3
      weeks and then for another 8 weeks were successfully established as the diabetes
      model(type II diabetes mellitus). The effects of feeding silk hydrates(SH) for 12
      weeks on the activities of insulin receptors and postreceptors were observed. The
      results showed that: 1) SH greatly improved the glucose tolerance of diabetic
      rats, but no effect on the secretion of insulin in rats with or without diabetes;
      2) Only the low-affinity constant of insulin binding rates(K2) in skeletal muscle
      cell membranes of diabetic rats fed with SH were obviously increased, the high
      affinity binding constant and the number of receptors were not changed; 3) the
      uptake of glucose in skeletal muscle of diabetic rats fed on SH was significantly
      increased. 4) SH partly improved the metabolism of serum lipids. The results
      indicated that SH could modulate the metabolism of blood glucose mainly through
      the mechanism on the activity of insulin postreceptor.

PMID- 12520960
TI  - [Study on nutrition composition and protein quality of a Chinese wild rice].
AB  - In order to exploit and develop the resource of a kind of Chinese wild
      rice[Zinania Lalifolia (Griseb) Turcz], the nutrition values of the Chinese wild
      rice from Luoma, Baoying, Hongze, Weishan and Tai lake were analyzed. The
      nutrients of Chinese wild rice per 100 g samples were protein 13.2 g, vitamin B1
      0.59 mg, vitamin B2 0.07 mg, vitamin E 0.29 mg, zinc 1.60 mg, iron 2.69 mg, and
      they were higher than those of white rice. The amino acid score of Chinese wild
      rice was 84, the first limiting amino acid was threonine, and the protein
      efficiency ratio(PER) was 2.75. These data showed that the Chinese wild rice was
      a good food resource with higher nutrition value, therefore, the ancient and
      novel food resource might be used in Chinese diet as the North American wild rice
      that was used in American diet.

PMID- 12520962
TI  - [Fasting serum glucose and its related indexes in 1477 middle aged and elderly
      people].
AB  - In order to study the relationship between higher fasting serum glucose (FSG) and
      other related indexes in middle aged and elderly people, FSG, triglyceride,
      cholesterol, urate and insulin of serum, blood pressure and body mass index(BMI)
      of 1477 men and women over 40 years of age were analyzed. The results showed that
      the level of FSG rised with the increase of age. The relations between FSG and
      cholesterol, urate, blood pressure and BMI were significant. The levels of
      cholesterol, urate, blood pressure and BMI in the abnormal FSG group were higher
      than those in the normal FSG group. There were positive relationships between FSG
      and cholesterol, urate, blood pressure, BMI, age, waist and buttock
      circumferences. The factors related to FSG were age, BMI, cholesterol and
      diastolic pressure by stepwise regression.

PMID- 12520963
TI  - [Development of a peristaltic inhibition model in mice].
AB  - Diphenoxylate was administered to mice at the dose of 5 mg/kg BW for the
      development of peristaltic inhibition model for formulating the examination
      procedure of health foods. An ink solution containing 5% charcoal was then
      administered 30 minutes later. The length of ink progradation of the small
      intestine of mice was calculated 25 minutes after the administration of ink. The
      results in this model was stable and reliable, and it was recommended to use this
      model to verify the function of health foods.

PMID- 12520964
TI  - [Effects of deoxynivalenol on proliferation and tumor necrosis factor-alpha
      secretion of human peripheral blood mononuclear cells in vitro].
AB  - Deoxynivalenol (DON) is one of the most common contaminating mycotoxins in food
      at high risk areas of esophageal carcinoma in China. The effects of DON on
      proliferation and tumor necrosis factor-alpha (TNF-alpha) secretion of human
      peripheral blood mononuclear (HPBM) cells in vitro were determined with flow
      cytometric (FCM) analysis, cell counting, MTT bioassay and ELISA method
      respectively. FCM analysis revealed that after HPBM were prestimulated with PHA
      for 48 h, the proliferation indexes(PI) of the cells treated with low
      concentration of DON (50-500 ng/ml) for 6 h were all dramatically lower than that
      of normal control (19.80%-26.01% vs 37.84%), while the PI of cells treated with
      high concentration of DON(1000-2000 ng/ml) for 24 h were higher than that of
      normal control (35.74%-34.37% vs 22.85%). Cell number counting and MTT bioassay
      results showed that at the presence of PHA, DON inhibited the proliferation of
      HPBM. Double antibody sandwich enzyme linked immunosorbent assay (ELISA) showed
      that the secretion of TNF-alpha in cells treated with DON(500-1000 ng/ml) was
      significantly lower than that in the control (P < 0.01). The results suggested
      that DON could either inhibit or stimulate cell proliferation depending on active
      time, concentration and PHA stimulation. In general, DON mainly inhibited the
      proliferation of HPBM and decrease TNF-alpha secretion in vitro. Thus, DON might
      have some negative impacts on human immunological system.

PMID- 12520965
TI  - [Determination of ochratoxin A by ELISA].
AB  - The determination of ochratoxin A by Enzyme-linked immunosorbent assay (ELISA),
      including the method of preparation of antigen and antibody, and the promising of
      ELISA in mycotoin determinations was introduced.

PMID- 12520966
TI  - [Study on the combined toxicity of aflatoxin B1 and deoxynivalenol].
AB  - The toxicity of aflatoxin B1(AFB1) and deoxynivalenol(DON) on the injury and
      repair of DNA was studied. Replicative DNA synthesis was used to detect the
      change of DNA synthesis in the primary rat hepatocytes at the S phase of cell
      cycle. The results showed that both AFB1 and DON could induce DNA synthesis in
      primary rat hepatocytes at the S phase of cell cycle, and an interaction between
      them was found. It suggested that AFB1 and DON produced marked effects on
      engendering tumor as genetoxic and nongenotoxic carcinogens complementarily.

PMID- 12520967
TI  - [Determination of trace elements in serum of tuberculosis patients].
AB  - In order to investigate the changes of molybdenum (Mo), zinc (Zn), copper (Cu),
      manganese (Mn) and seleniumin (Se) level in serum of tuberculosis patients, the
      concentrations of Mo, Zn, Cu, Mn and Zn in serum of 30 tuberculosis patients and
      30 health controls were determined by inductively coupled plasma mass
      spetrometry. The results showed that compared with the control group, the levels
      of Mo, Zn, Cu, and Se in the serum of tuberculosis patients decreased
      significantly (P < 0.001), but the change of Mn was insignificant (P > 0.05).

PMID- 12520968
TI  - [Methionine synthase and neural tube defects].
AB  - It has been indicated lately that higher plasma homocysteine is one of the risk
      factors in neural tube defects(NTDs) and vascular disease. Methionine synthase is
      a key enzyme in homocysteine metabolism. The defects of methionine synthase
      activity could result in hyperhomocysteinemia and methionine auxotrophy. The gene
      mutations of methionine synthase with the epidemiological studies of NTDs are
      reviewed in this paper. It is considered that the gene mutations of methionine
      synthase can not make a relation to NTDs and hyperhomocysteine, but methionine
      synthase reductase may be a clue for the study on NTDs in the future.

PMID- 12520969
TI  - [Study on the revision of hygiene standard for fresh-cream cake].
AB  - In order to revise the hygiene standard for fresh-cream cake, 44 samples were
      examined. With regard to the specific selling condition and the results
      inspected, a reference for acid value, peroxide value, bacterial colony forming
      efficiency and mould count was proposed. Moreover the yeast count was suggested
      as one of the hygienic standard for GB7099 too. The result of this study could be
      used as a reference for developing the law on the hygienic inspection and control
      of fresh-cream cake.

PMID- 12520970
TI  - [Effect of estrogen on the expression of c-myc protein of bone in mice].
AB  - In order to study the mechanism by which estrogen effects on bone, the effect of
      estrone on expression of c-myc protein in the epiphyseal plate of fetal mouse
      long bone was detected by immunohistochemistry procedure in vitro. The result
      showed that the concentrations of estrone areas of positively staining cells
      increased significantly in proliferative zone at 10(-9) mol/L, in proliferative
      zone and resting zone at 10(-8) mol/L, and in resting zone, proliferative zone
      and hypertrophic zone at 10(-7) mol/L respectively. It was considered that
      estrogen might enforce endochondral bone formation by enhancing expression of c
      myc in long bone.

PMID- 12520971
TI  - [Effect of pretreatment on the measurement of folate in foods].
AB  - In order to measure the content of folate in foods accurately, to hydrolyze and
      extract folate in foods with suitable pretreatment is necessary because folate in
      foods is always in polyglutamate structure. The pretreatment of samples including
      hydrolysis with phosphate buffer(0.05 mol/L, pH 6.8) once or twice, with chick
      pancreatin, protease and/or amylase, and a combining of trienzyme methods was
      compared and discussed. A microbiological method with lactobacillus casei was
      used. A high result of folate in foods could be obtained when extracting folate
      enriched samples or vegetables with phosphate buffer once or twice respectively,
      or hydrolyzing "extracted oral liquids" with chick pancreatin, or when extracting
      samples rich in protein and/or starch with trienzyme. The RSD of interassay and
      intrassay were 6.5%-9.9% and 3.5%-14.1% respectively, and the recovery rate was
      86.8%-106.8%.

PMID- 12520972
TI  - [Hygienic status of deep fried oils in 1998 and the contrast with 10 years ago].
AB  - The hygienic status and influence factors of deep fried oil were studied. The
      samples from 29 individual producers, 38 state-operated or cooperated restaurants
      and 30 joint-invested enterprises were collected to investigate the hygienic
      condition on the spot, and to analyze the acid value(AV), carbonyl value (COV)
      and polar compound(PC) with national standard methods(GB). The data showed that
      the degree of rancidity of the deep fried oils varied with different types of
      oil, refinement of oil and the kind of fried food. Comparing with the results
      obtained a decade ago, COV was decreased while PC was increased. It was
      suggested: (1) to specify some types of oil for flying foods; (2) to develop some
      quick methods for checking fried oil; (3) to improve the method for detecting PC
      for solid oil at ordinary (indoor) temperature; (4) to study the quality and
      safety of fried foods prepared by solid oils.

PMID- 12520973
TI  - Nurses have the power to be advocates.

PMID- 12520974
TI  - Preventing and managing dehydration.
AB  - Sufficient body water and electrolyte homeostasis are essential for healthy
      physiologic functioning. Nurses are key to preventing, detecting early, and
      treating fluid and electrolyte imbalances. Dehydration significantly alters both
      physical and psychological functioning, and older adults are at increased risk.
      Identifying fluid disorders early can prevent complications and reduce hospital
      stays. Understanding the mechanisms of fluid homeostasis enables nurses to
      assess, prevent, and collaborate in managing isotonic, hypertonic, and hypotonic
      dehydration.

PMID- 12520975
TI  - Nurses and back injuries.

PMID- 12520976
TI  - Diabetes expertise: a subspecialty on a general medical unit.
AB  - A medical unit developed a subspecialty in diabetes care by increasing the
      expertise of its staff nurses. A task force was formed to set goals and create an
      action plan. An educational curriculum was developed, implemented, and evaluated.
      Medical staff nurses were integrated as diabetes educators and now provide 24
      hour diabetes specialty care coverage for the hospital.

PMID- 12520977
TI  - Perspectives of caregivers of stroke survivors: implications for nursing.
AB  - The majority of stroke survivors receive home care. To offer better support, home
      caregivers and nurses must understand the caregiving experience. This knowledge
      will enable nurses to help home care givers provide more effective care and
      conserve their own resources.

PMID- 12520978
TI  - Genetic advances in coronary artery disease.
AB  - Traditionally, many health care providers consider clinical genetics to be a
      field that only applies to specialists who provide services to individuals with
      rare single-gene or chromosomal disorders. But this concept is changing rapidly.
      In the year 2000, nine of the ten leading causes of mortality, including heart
      disease, have identified genetic components. As patient advocates and health care
      providers, nurses have a responsibility to become familiar with genetic advances
      and translate this knowledge into improved individualized care for patients.

PMID- 12520979
TI  - Gleevec: zeroing in on cancer.

PMID- 12520980
TI  - How do you spell relief?

PMID- 12520981
TI  - An evidence-based practice study: critical events following eye surgery in one
      ophthalmic PACU.

PMID- 12520982
TI  - A brighter future for the AIDS patient.
AB  - This article explores the etiology, medical and surgical treatment, and care of
      the acquired immune deficiency syndrome (AIDS) patient with cytomegalovirus (CMV)
      retinitis. CMV retinitis is the most common intraocular infection as well as the
      leading cause of vision loss in people with AIDS. CMV, part of the herpesvirus
      group, is an opportunistic pathogen that is transmitted through body fluids. Both
      the human immunodeficiency virus (HIV) and the herpesvirus are factors in
      predisposing retinal tissue to CMV. CMV usually remains dormant in a healthy
      immune system. However, in people who are immunosuppressed, the virus can become
      active and cause infections in the GI tract, lungs, and central nervous system,
      as well as in the eyes.

PMID- 12520983
TI  - An assessment tool for screening ROP in the preterm infant.
AB  - An increased incidence of retinopathy of prematurity (ROP) parallels the
      increased incidence of viable births at earlier gestational ages. However,
      advancements in laser therapy can treat ROP and ultimately prevent blindness.
      This paper describes the development, implementation, and evaluation of a tool
      that consistently documents ROP assessments by medical staff, as well as
      pertinent medical history necessary to safely manage this critical population.
      The assessment tool was designed for an outpatient ophthalmology clinic. The
      outpatient population included all infants delivered at or transferred to the
      neonatal intensive care unit of a large university hospital located in the
      Midwestern United States. The infants were considered at risk for ROP if they
      weighed less than 1500 grams or if they had a gestational age of less than or
      equal to 34 weeks. At any given time, the outpatient clinic manages from 50 to 70
      infants. Implementation of the tool increased consistency in documentation by
      medical staff and guided the initial assessment for nursing and technical staff
      members.

PMID- 12520984
TI  - Eye safety in the workplace.

PMID- 12520986
TI  - How to acknowledge people without turning them off.

PMID- 12520985
TI  - Management of anxiety in the refractive surgery patient.
AB  - Refractive surgery has rapidly evolved to become a preferred alternative for the
      correction of refractive errors. As the quest to obtain faster visual recovery,
      fewer complications, and early stability continues, there is little in the
      literature that addresses the anxiety experienced by most refractive surgical
      patients. Although vision-correction surgery uses highly technical and precise
      procedures, the need to develop therapeutic caring and communicative techniques
      for these patients has not been adequately addressed. There has been insufficient
      research in the literature focusing on the patient's fear. Respecting the
      patient's fear and concerns and supporting them by developing a humanistic
      approach to patient care may prove to be beneficial to the patient and the
      refractive team.

PMID- 12520987
TI  - Researchers examine the benefits of potent antiretroviral therapy and treatment
      compliance among patients with HIV.

PMID- 12520988
TI  - The great HIPAA ripoff.

PMID- 12520989
TI  - When your employees are your patients, too.

PMID- 12520990
TI  - Non-shrinking composite matrix shows promise for restorations.

PMID- 12520991
TI  - Are all powder-free gloves the same?

PMID- 12520992
TI  - Meet Dr. Vince Mack. Interviewed by Jeff Mertens.

PMID- 12520993
TI  - Questions and answers about HIPAA--Part Two.

PMID- 12520994
TI  - And now, the rest of the staff.

PMID- 12520995
TI  - [Nutritional anemia of pregnancy in the Zulia state. 30 years later].
AB  - Thirty years ago, we reported a high frequency of nutritional anemia among
      pregnant women of low socioeconomic class, from Zulia State, Venezuela. Today,
      preliminary results, show an increase of anemia from 20% in the year of 1972 to
      44% at the end of the first trimester of gestation, and from 53% to 63% at the
      end of the third trimester. These results could be the reflection of the
      impairment of the economic conditions in the country and the failure of the
      prenatal care services in preventing or treating anemia in pregnancy.

PMID- 12520996
TI  - [Prevalence of giardiasis in day care centers in San Francisco municipality,
      state of Zulia, Venezuela].
AB  - The number of children Day Care Centers has increased progressively in
      underdeveloped countries. These Institutions offer conditions that facilitate the
      transmission of enteric agents. The aim of the present study was to determine the
      prevalence of Giardiasis in Day Care Centers from San Francisco municipality,
      Zulia state, Venezuela. A poll was applied to collect personal and clinical data.
      Fecal samples from 82 children of one or another sex, between 11 months and 6
      years old, who normally assist to four Day Care Centers of the municipality
      mentioned above, were analyzed. The samples were processed by fresh examination,
      lugol temporal coloration and the formol-ether technique. A percentual analysis
      was applied for the statistical study. From the 82 processed samples, 37 (45.1%)
      showed the presence of Giardia lamblia. The clinical symptoms most frequently
      observed in the study were abdominal pain, diarrhea, weight loss and inappetence.
      Statistical results did not show a significant difference of this parasitic
      disease with relationship to sex; however, there is a predominance in children of
      school age (75%). The result of this work shows a high prevalence of Giardiasis
      in Day Care Centers of the municipality studied, which suggests that this
      institutions gather the conditions that facilitate the transmission of this
      flagellate, and that preventive measures must be put into practice.

PMID- 12520997
TI  - [Carrier detection of Duchenne/Becker muscular dystrophy by analysis of STRs loci
      linked to the gene of dystrophin in Venezuelan families].
AB  - The Duchenne/Becker Muscular Dystrophy (DMD/BMD) is an X linked recessive lethal
      disease. The female carrier will transmit the disease gene to half of her sons
      and half of her daughters; half of the daughters will be carriers, while half
      will be normal. Half of the sons will be normal and, on average, half will have
      the disease. It is of particular relevance to be able to detect carrier status
      among female relatives of the patients for genetic counseling and prenatal
      diagnosis. The method of Short Tandem Repeat (STR) sequence polymorphism analysis
      can determine haplotype at normal status or at risk status and, to establish
      genetic linkage between the mutated gene and the segregated haplotype. We have
      analyzed 105 members from 15 unrelated Venezuelan families with one or more
      siblings affected with DMD/DMB and 7 unrelated males. Of the 105, 37 were male
      (26 affected and 11 normal) and 68 were female. STR sequences (STR44, STR45,
      STR49, STR50, STR3'DYS) of the gene of the Dystrophin were amplified by
      polymerase chain reaction (PCR) to analyze allelic polymorphism in the families.
      Five of the 15 families (33%) had a deletion of one or several of the exons. Of
      the 68 females, 27 (39.7%) were carriers, 27 (39.7%) were non-carriers and in 14
      cases (20.58%) it was not possible to reach a definitive diagnosis. The
      definitive diagnosis could be established in 79% of the females. This analysis
      also shows that the mutation occurred on the grandpaternal X chromosome in one
      family. Hemizygocity was detected and carrier status ascertained in the mother of
      other patient and in one family we were able to do prenatal diagnosis. The
      germinal mosaicism could not be excluded in 3 patients.

PMID- 12520999
TI  - [Clonal chromosomal anomalies in colorectal tumors].
AB  - Colorectal tumors constitute a reason of frequent consultation in
      gastroenterology services in the world. They constitute the second cause of
      mortality in the world and the fourth cause of mortality for cancer in Venezuela.
      It usually begins as a polyp that becomes malignant due to a mutation at the
      level of the genetic code that controls the growth and the repair of cells. The
      present work reports the clonal chromosomal abnormalities observed in 15 samples
      from benign tumors as well as malignant colorectal tumors and to relate these
      findings. There were clonal chromosomal anomalies in 11/15 (73.33%), 4
      corresponded to carcinomas and 7 to adenomatous polyps. In 7/11 (63.6%) there
      were anomalies of the monosomy type in the chromosomes 8 and 22, other anomalies
      corresponded to trisomy of the chromosomes 11 and 18, and a single case with a
      structural anomaly that corresponded to a del(17p). The chromosomal anomalies in
      adenomatous polyposis have been related with the beginning of malignant disease
      and, in the case of carcinomas, it has been related with progression of the
      illness toward metastasis and death. The use of this tool could be used as a
      prognostic factor for patients with non familial adenomatous polyposis.

PMID- 12520998
TI  - [Susceptibility to the infection of Anopheles nuneztovari Gabaldon and Aedes
      aegypti L with Romanomermis iyengari Welch (Rhabditida: Mermitidae)].
AB  - A laboratory-based study was performed in order to assess the infestation
      capacity of the mosquito parasite nematode Romanomermis iyengari Welch, on
      Anopheles nuneztovari Gabaldon and Aedes aegypti L. For each mosquito species,
      nine hundred (900) I to III instars larvae were taken. These larvae were infested
      with pre-parasitic larvae of R. iyengari in proportions of 5:1 and 10:1. The
      infestation averages obtained were 3.9 and 6.7 for Anopheles nuneztovari, and 1.9
      and 4.7 for Aedes aegypti respectively. Mortality ranked between 95 and 100% for
      both mosquito species and Anopheles nuneztovari showed the highest susceptibility
      to the nematode parasitism.

PMID- 12521000
TI  - [Organizational stress and noise exposure in workers at the packing plant of a
      brewer factory].
AB  - The purpose of this study was to identify and to evaluate the psychosocial
      factors that produce organizational stress in workers at the packing plant of a
      brewering industry, and to determine the influence of industrial noise in the
      occurrence of stress at work. The Questionnaire of Organizational Stress of the
      ILO/WHO was applied to 163 workers to evaluate psychosocial factors at work, and
      the socio-demographic characteristics were explored on an individual basis. The
      equivalent continuous sound level (Leq) was determined and the octave band were
      determined with a sonometer according to the COVENIN guidelines. Total stress was
      found in 55 workers (33.74%). Of those, 42 workers were in an intermediate level
      (25.76%) and 13 workers (7.98%) were in the stress level (p < 0.0001). The
      occurrence of pondered stress was 100%, classified as: influences of the leader
      (14.00 +/- 7.27; 87.7%), organizational structures (12.36 +/- 5.14; 93.3%) and
      organizational climate (11.83 +/- 5.09; 95.1%). The mean of total and pondered
      stress showed an upward tendency as age and labor antiquity increased (p < 0.05).
      Leq was in a range of 87.9-100 dB(A), which exceeds the threshold value limit.
      There was no association between Leq was stress. The level of total stress that
      these workers perceive is similar to that described in other studies. The
      pondered stress becomes a highly sensitive variable to determine which
      psychosocial factors produce stress. This can be used for implementing control
      and preventive measures of organizational stress.

PMID- 12521001
TI  - [Fibrinogen: cardiovascular risk factor].
AB  - This paper demonstrate that plasmatic fibrinogen is a risk factor for ischaemic
      cardiovascular disease. Apart from its hemostatic functions, it has an important
      role in the atherothrombotic process. Prospective studies in a normal population
      and on patients with pre-existent cardiovascular disease demonstrate that
      fibrinogen is a predictor of cardiovascular events, either as first episode or
      recurrence. It is also reviewed a epidemiological study which is been carried out
      in Venezuela as a pilot study for Latinamerica because our population is
      different from those where the studies have been performed up to now. It is also
      mentioned the factors that influence the fibrinogen levels, some of them can be
      modified which could be useful for the prevention of the disease. It is
      considered the necessity of further studies to evaluate the benefit of the
      control of the fibrinogen level.

PMID- 12521002
TI  - Herbal products: what's in the bottle? ...and does it really work?

PMID- 12521003
TI  - How dangerous are "glow sticks"?

PMID- 12521004
TI  - Smallpox vaccination: pediatric academy perspective.

PMID- 12521005
TI  - Swaddling: an option to encourage "back to sleep"?

PMID- 12521006
TI  - Hope for peanut allergy?

PMID- 12521007
TI  - Product recalls. Baby walkers...IKEA stuffed teddy bears...and BRIO caterpillar
      pull toy.

PMID- 12521008
TI  - Enterococcus faecalis: an unusual cause of meningitis in HIV-infected patients.
AB  - A case of a severely immunosuppressed HIV-infected man with meningitis caused by
      Enterococcus faecalis is presented. E faecalis is a distinctly unusual cause of
      bacterial meningitis in patients with HIV infection and should be considered in
      the differential diagnosis of purulent meningitis in such patients to ensure
      optimal empiric treatment.

PMID- 12521009
TI  - [Secret drug tribulations and French legislation].
AB  - From an official Montpellier prefecture paper of 18th century, we are interested
      in a secret drug from Provence origin: the Irroe powder. This purgative will pass
      from "secret" drug status to "patent" drug. It's notoriety will come from its
      arrival to Paris. The law of 21th germinal year XI, the decret of 25 prairial
      year XIII and this of 18th 1810 imposed to give the drug composition to an
      official status; that examined and permit it's sale. This secret will be produce
      for half century.

PMID- 12521010
TI  - Non-gonococcal urethritis due to Chlamydia trachomatis: the Ibadan experience.
AB  - Using a qualitative amplified enzyme-linked immunoassay, two hundred and eighty
      nine male patients with symptoms and signs suggestive of urethritis were
      investigated for Chlamydia trachomatis as a cause of non-gonococcal urethritis
      (NGU). Ninety-one (31.49%) of the 289 male patients investigated had gonococcal
      urethritis whilst 198 (68.51%) had NGU out of which 112 (56.60%) had chlamydial
      urethritis and 14 (7.1%) had Trichomonal urethritis. Two (6.7%) of the control
      subjects had C. trachomatis in their urethral swabs. The difference in the
      occurrence of C. trachomatis between the patients and the controls was highly
      statistically significant (P<0.001). The age range of peak incidence among the
      patients investigated was 20-29 years. Thirteen of the men treated for gonorrhoea
      still had watery urethral discharge and irritation and were diagnosed as having
      post-gonococcal urethritis (PGU), eleven (84.6%) of whom had C. trachomatis
      demonstrated in their urethral swabs. We were able to demonstrate a significant
      difference in clinical symptoms in men with gonorrhoea and NGU but only a slight
      difference between men with chlamydia-positive NGU and chlamydia-negative NGU.

PMID- 12521011
TI  - Placement, performance and complications of the Ash Split Cath hemodialysis
      catheter.
AB  - A tunneled catheter is the alternative vascular access for those patients in need
      of hemodialysis who cannot undergo dialysis through an arterio-venous fistula or
      a vascular graft. This study was undertaken to evaluate the performance of the
      Ash Split Cath, a 14 French chronic hemodialysis catheter with D-shaped lumens
      and a Dacron cuff. After tunneling through a transcutaneous portion the catheter
      enters the venous system, where it splits into two separate limbs. Data regarding
      catheter positioning, function and adequacy of dialysis were collected from two
      hemodialysis facilities. Twenty-eight Ash-split catheters were placed in 28
      patients, with no complications, and immediate technical success was 100%.
      Patients were followed up for a total of 7,286 catheter days. No catheter-related
      infections were observed. Only one catheter failed after 15 days, with a primary
      catheter patency of 96% for the whole study length. Mean blood flow was 303 +/-
      20 ml/min at 1 week after insertion, 306 +/- 17 ml/min at 3 months, 299 +/- 44
      ml/min at 6 months, and 308 +/- 16 ml/min at 12 months. With a mean dialysis
      session duration of 234 +/- 25 minutes, adequate dialysis dose was observed for
      96% of catheters, as reflected by a mean urea reduction ratio (URR) of 71% +/- 8
      or a mean urea kinetic modeling, or Kt/V, value of 1.51 +/- 0.3 during follow up.
      In conclusion, compared with previous studies we report the best permanent
      catheter performance, confirming that the Ash-split catheter is a good
      alternative for vascular access in hemodialysis patients who are not candidates
      for surgical A-V fistula or graft placement.

PMID- 12521012
TI  - Effects of heavy-ion radiosurgery on the hemopoietic function of the silkworm
      Bombyx mori.
AB  - To study the effects of heavy-ion radiosurgery on the hemopoietic function of a
      silkworm, hemopoietic organs of larvae were locally irradiated with carbon-ion
      beams, and the changes in the hemocyte density and in the hemocyte function were
      investigated. When the larvae were irradiated by 50 Gy to 300 Gy carbon ions on
      the 3rd day of the 4th instar, the hemocyte densities did not change for a while,
      though they gradually increased at a later stage, but were finally still
      significantly lower than those of unirradiated controls. The hemocyte densities
      of the larvae irradiated at different developmental stages showed suppressed
      increments, and carbon-ion irradiation given to larvae at early stages compared
      to the later stages had a significant suppressive effect on the hemocyte
      densities. On unilateral irradiated larvae a hemocyte intermediate increment
      between those of bilateral irradiated larvae and unirradiated controls was
      observed. The percentage of dead hemocytes was obviously higher for irradiated
      larvae than unirradiated controls during the later 5th instar. Thus, it is
      evident that carbon-ion radiosurgery on hemopoietic organs of silkworm induced
      not only a quantitative change, but also a qualitative change in the hemocytes.

PMID- 12521015
TI  - Integrating population outcomes, biological mechanisms, and research methods in
      the study of human milk and lactation. Proceedings of the 10th International
      Conference of the Society for Research on Human Milk and Lactation (ISRHML).
      September 15-19, 2000. Tucson, Arizona, USA.

PMID- 12521013
TI  - Evidence that exclusive use of Follistim may produce better pregnancy results
      than the use of Gonal-F following in vitro fertilization (IVF) - embryo transfer
      (ET).
AB  - PURPOSE: To evaluate whether the equal mixture of human menopausal gonadotropin
      (hMG) to recombinant (r) follicle stimulating hormone (FSH) for controlled
      ovarian hyperstimulation (COH) adversely affects outcome following in vitro
      fertilization (IVF). Furthermore, to determine if the specific rFSH preparation
      used has any differing effects on outcome. METHODS: Retrospective study of women
      using the luteal phase leuprolide acetate-gonadotropin COH regimen. Outcome
      measures included clinical and viable pregnancy rates (PRs) and implantation
      rates. RESULTS: The clinical and viable PRs and implantation rates were
      significantly lower in the group receiving exclusively Gonal-F. Addition of hMG
      to the treatment protocol not only did not lower the PRs further, but in fact
      seemed to obviate the adverse effect of Gonal-F. CONCLUSION: Since exclusive use
      of Gonal-F did not adversely affect fertilization rates or quality of embryos we
      suspect its exclusive use in some way makes the uterine environment less
      receptive.

PMID- 12521016
TI  - Redefining the Reserve response.

PMID- 12521017
TI  - My brilliant career--clinical governance. Oar inspiring. Interview by Lyn
      Whitfield.

PMID- 12521018
TI  - Adverse reactions to bovine proteins: changing patterns, mechanisms and
      treatment. December 13-15, 2001. Milan, Italy.

PMID- 12521019
TI  - Flavonoids in cell function. Proceedings of the 19th National Meeting of the
      American Chemical Society. San Francisco, California, USA. March 29-30, 2000.

PMID- 12521020
TI  - Instrumentation, control and automation 2001 (ICA2001). Proceedings of the 1st
      IWA International Conference on Instrumentation, Control and Automation. Malmo,
      Sweden. June 3-7, 2001.

PMID- 12521021
TI  - The cardiovascular risk in special populations: hypertensive disease in women.
      Bologna, Italy. September 22-23, 2000.

PMID- 12521022
TI  - Social and health insurances in agriculture. Lublin, 23-25 October 2002. IX
      International Symposium on Ergonomics, Work Safety and Occupational Hygiene.

PMID- 12521023
TI  - Cumulative Index: a glimpse into otolaryngology's past.

PMID- 12521024
TI  - Janus on the mudflats.

PMID- 12521026
TI  - Bibliography of current world literature.

PMID- 12521025
TI  - Guiding drug discovery through 2003.

PMID- 12521027
TI  - Antithrombotic drug market.

PMID- 12521028
TI  - Drotrecogin alpha (activated).

PMID- 12521029
TI  - What makes a good forecaster?

PMID- 12521030
TI  - Pituitary tumour therapy: using the biology.
AB  - Pituitary tumours are benign but cause significant problems, both because of
      their compressive effects on brain structures and also because of the syndromes
      of hormone excess or deficiency that they can cause. Endocrine therapy has become
      increasingly successful, with the development of dopamine agonists and
      somatostatin analogues. Recently growth hormone receptor antagonists have been
      developed by modification of the GH molecule. It is likely that further advances
      based on our understanding of the biology will dramatically improve the treatment
      of these tumours.

PMID- 12521031
TI  - Strengthening WHO's position should be a priority for the new Director-General.

PMID- 12521032
TI  - WHO must continue its work on access to medicines in developing countries.

PMID- 12521033
TI  - WHO should work to develop Alzheimer's standards.

PMID- 12521034
TI  - WHO should build partnerships with the pharmaceutical industry to improve public
      health.

PMID- 12521035
TI  - WHO's drugs work must continue.

PMID- 12521036
TI  - New WHO leader should keep health of the poor at the heart of the political
      agenda.

PMID- 12521037
TI  - New WHO leader should aim for equity and confront undue commercial influences.

PMID- 12521038
TI  - Cancer should be prioritised on WHO agenda.

PMID- 12521039
TI  - New leader should re-establish WHO's credibility.

PMID- 12521040
TI  - Communication, cooperation, leadership--priorities for the new WHO Director
      General.

PMID- 12521041
TI  - Keep polio eradication at the top of WHO's agenda.

PMID- 12521042
TI  - WHO should focus on improving health systems.

PMID- 12521043
TI  - Outcomes of planned home births in Washington State: 1989-1996.

PMID- 12521044
TI  - Outcomes of planned home births in Washington State: 1989-1996.

PMID- 12521045
TI  - [Boulduc's dynasty, apothecaries in Paris in XVIIth an XVIIIth centuries
      (following the article published in Revue d'histoire de la pharmacie, 2001, no.
      331, p. 339-354)].
AB  - Like his father Simon Boulduc, Gilles-Francois Boulduc worked as a demonstrator
      in chemistry at the Jardin Royal. He was the apothecary of King Louis XIV and
      King Louis XV, a member of the Academie Royale des Sciences. In addition he was
      appointed alderman of the town of Paris. He worked in Paris rue des Boucheries
      and went into partnership with another apothecary, Claude Pia. He was also the
      drug supplier of the Duke de Saint-Simon who quoted him several times as a Royal
      apothecary in his Memoires. Gilles-Francois Boulduc's main chemistry research
      work is presented in this article.

PMID- 12521046
TI  - [About "Almanach de la Pharmacie Brunot", pharmaceutical advertising in
      "Limousin" at the beginning of the XXth century].
AB  - It seems necessary to bring further information after Mr. Portenart's paper. The
      "Almanach" published by "Pharmacie Brunot" was a good example of advertising
      pharmacists used at the beginning of the XXth century. It is not abnormal and
      advertising were numerous during the first fifty years of the century.

PMID- 12521047
TI  - Transmission measurement based on STM observation to detect the penetration depth
      of low-energy heavy ions in botanic samples.
AB  - The penetration depth of low-energy heavy ions in botanic samples was detected
      with a new transmission measurement. In the measurement, highly oriented
      pyrolytic graphite (HOPG) pieces were placed behind the botanic samples with
      certain thickness. During the irradiation of heavy ions with energy of tens of
      keV, the energetic particles transmitted from those samples were received by the
      HOPG pieces. After irradiation, scanning tunneling microscope (STM) was applied
      to observe protrusion-like damage induced by these transmitted ions on the
      surface of the HOPG. The statistical average number density of protrusions and
      the minimum transmission rate of the low-energy heavy ions can be obtained. The
      detection efficiency of the new method for low-energy heavy ions was about 0.1-1
      and the background in the measurement can be reduced to as low as 1.0 x 10(8)
      protrusions/cm2. With this method, the penetration depth of the energetic
      particles was detected to be no less than 60 micrometers in kidney bean slices
      when the slices were irradiated by 100 keVAr+ ion at the fluence of 5 x 10(16)
      ions/cm2.

PMID- 12521049
TI  - Innovation, cooperation keys to terror response.

PMID- 12521048
TI  - Effects of space flight, clinorotation, and centrifugation on the substrate
      utilization efficiency of E. coli.
AB  - Cultures of Escherichia coli grown in space reached a 25% higher average final
      cell population than those in comparably matched ground controls (p<0.05).
      However, both groups consumed the same quantity of glucose, which suggests that
      space flight not only stimulated bacterial growth as has been previously
      reported, but also resulted in a 25% more efficient utilization of the available
      nutrients. Supporting experiments performed in "simulated weightlessness" under
      clinorotation produced similar trends of increased growth and efficiency, but to
      a lesser extent in absolute values. These experiments resulted in increases of
      12% and 9% in average final cell population (p<0.05), while the efficiency of
      substrate utilization improved by 6% and 9% relative to static controls (p=0.12
      and p<0.05, respectively). In contrast, hypergravity, produced by centrifugation,
      predictably resulted in the opposite effect--a decrease of 33% to 40% in final
      cell numbers with corresponding 29% to 40% lower net growth efficiencies
      (p<0.01). Collectively, these findings support the hypothesis that the increased
      bacterial growth observed in weightlessness is a result of reduced extracellular
      mass transport that occurs in the absence of sedimentation and buoyancy-driven
      convection, which consequently also improves substrate utilization efficiency in
      suspended cultures.

PMID- 12521050
TI  - Hospitals manage assets via Intellamed.

PMID- 12521051
TI  - Few IDNs have what it takes to self-contract.

PMID- 12521052
TI  - Iowa Health finds new frontier in data cleaning.

PMID- 12521053
TI  - A naive accelerometer acting in the continuum range.
AB  - The space experiment TRAMP (Thermal Radiation Aspects of Migrating Particles)
      flown in 1999 onboard the mission Foton 12 sponsored by the European Space Agency
      (ESA), was conceived to reveal and measure a new kind of forces, named Thermal
      Radiation Forces (TRF). The experiment was dramatically disturbed by the
      occurrence of undesired convective motions due to the rotation of the spacecraft.
      Apart from that, corrosion occurred in some parts of the flight apparatus,
      resulting in the presence of gas bubbles inside the experimental liquid,
      completely compromising the results. Consequently, the experiment did not allow
      to reveal and/or to measure TRF, but it turned out to be useful in another way,
      as a very sensitive accelerometer, since the accelerations deduced from velocity
      measurements concurred with those measured by the Quasi-Steady Acceleration
      Measurement (QSAM) system.

PMID- 12521054
TI  - Interactions among dietary fat, mineral status, and performance of endurance
      athletes: a case study.

PMID- 12521055
TI  - E-Z shopping. E-procurement can buy efficiencies, savings.

PMID- 12521056
TI  - [From Institut Pasteur to Radio Luxembourg. The surprising history of Tho-Radia].
AB  - The authors study of the history of "Tho-Radia", a cream with base of thorium and
      radium, launched in 1933 by Dr Alfred Curie and a pharmacist, Alexis Moussali.
      Tho-Radia disappears near 1960.

PMID- 12521057
TI  - [Hufeland (1762-1836) and homeopathy].
AB  - In 1796 homeopathy was born by the publication of an Hahnemann's article in a
      periodic founded by C. W. Hufeland, a German physician, Professor in Iena, who
      was friendly with Hahnemann during more of thirty years. This periodic, which
      defended the experimental philosophy and was devoted to the practical medicine,
      will be nevertheless the mean instrument to spread Hahneman's ideas until the
      issue of the Organon in 1810. Also, the thought of Hahneman looks us as built up
      itself partly in large connection with the ideas of this review, and probably
      still more with the Hufeland's writings. The prolix author Hufeland published in
      1795, 1796, and 1800, at the same time of homeopathy's foundation, three main
      works that Hahnemann has certainly distinguished. Between 1825 and 1830, Hufeland
      tried to put himself as an unprejudiced judge of the attacked homeopathy. His
      pleading, as well as his straight critical remarks is an authentic and right
      enough testimony, only made a little false by the state of medicine in these
      days. He put up the controversy at least so high as the today's polemics.

PMID- 12521058
TI  - Using OSCE-based evaluation: curricular impact over time.
AB  - The Objective Structured Clinical Examination (OSCE) is becoming more widely used
      for performance assessment in dentistry. The department of pediatric dentistry at
      Baylor College of Dentistry (BCD) began incorporating the OSCE into its
      curriculum in 1995. This article describes the evolution of the department's use
      of the OSCE and its impact on teaching and the curriculum. The discussion focuses
      on logistics and station design, curricular content and order, student anxiety,
      writing and scoring exams, and curriculum assessment. BCD has found that using an
      OSCE-based testing format is time-consuming and labor-intensive, but provides
      unprecedented feedback about students' understanding and pinpoints areas of
      confusion. The demands of an OSCE-based testing format reveal that students can
      master, to the level of competency, only a finite amount of information in a
      given time period. The timed, interactive aspects of the OSCE create high levels
      of student anxiety that must be addressed. Writing and scoring OSCE items are
      different from traditional test items. The OSCE is a valuable mechanism to assess
      the students' progress toward competency. This review of the process of
      incorporating OSCEs into a curriculum is the foundation for future assessment of
      the OSCE and its use for curricular improvement.

PMID- 12521059
TI  - A comparison of student performance in a simulation clinic and a traditional
      laboratory environment: three-year results.
AB  - With simulation clinics, dental schools have improved their preclinical
      laboratories to provide a more realistic clinical teaching environment. However,
      there is very little data to support the assumption that these facilities
      actually improve student performance of technical skills. This study compared the
      scores of two fixed preparations for full cast crowns by third-year dental
      students. One of the preparations was made in the simulation clinic manikin, and
      the other was prepared on the bench top. Three prosthodontic faculty members
      scored the preparations in the areas of occlusal reduction, axial reduction,
      resistance and retention, and margination. The study also compared the
      performance of three classes of dental students: one class with no experience in
      the simulation clinic, one with one year of experience, and one with two years of
      experience. The amount of time since completing the fixed prosthodontics course
      among the students was also evaluated. This was done because the third-year
      students at the University of Iowa rotate through a series often-week clerkships
      rather than a comprehensive care model. (Therefore, not all students start
      clinical prosthodontics at the same time.) In addition, all student participants
      completed a questionnaire that addressed their perception of their clinical
      readiness prior to treating their first fixed prosthodontic patient. When we
      compared the classes of years 1, 2, and 3 by average preparation score, we found
      a significant difference among the scores for teeth prepared on the bench top (p
      = 0.0001) but not for the teeth prepared in the mannequin (p = 0.1176). For Year
      1 (no simulation clinic experience), the amount of elapsed time following
      completion of the fixed prosthodontic course was not significant for the tooth
      prepared on the bench top or in the manikin (p = 0.57113 and 0.0661). For Year 2
      (one year of simulation clinic experience), the elapsed time following completion
      of the fixed prosthodontic course was significant for the tooth prepared on the
      bench top (p = 0.0482), but it was not significant for the tooth prepared in the
      manikin (p = 0.2968). For Year 3 (two years of simulation clinic experience), the
      amount of elapsed time following completion of the fixed prosthodontic course was
      not significant for the tooth prepared on the bench top or in the manikin (p =
      0.7275 and 0.6007). The questionnaire revealed that, in general, the majority of
      the students perceived their clinical readiness as more than adequate. These
      results are mixed in that students with more bench top experience scored better
      on the bench top, and students with more manikin experience scored equally in
      both environments.

PMID- 12521060
TI  - Trends in dental specialty education and practice, 1990-99.
AB  - Policy issues related to dental specialty education and practice have been the
      responsibility of the American Dental Association's Council on Dental Education
      and Licensure. In 2001, the council concluded a comprehensive study of the ADA
      recognized dental specialties that included a review of specialty practice and
      the practice environment, membership in specialty organizations, requirements and
      trends in board certification, advances in research and technology related to
      each specialty, and trends in advanced specialty education. This paper provides
      an overview of the results of this study and the council's analysis of data and
      information provided by the dental specialty organizations and the ADA Survey
      Center with an emphasis on dental specialty education. The council concluded that
      none of the dental specialties should be considered for rerecognition, but
      identified concerns regarding the shortage of qualified faculty and educational
      program directors. As a result of the council's study, recommendations have been
      made to the dental specialty organizations and ADA-recognized dental specialty
      certifying boards that they continue to monitor the number of board-certified
      specialists and identify ways to increase the number of board-certified
      specialists.

PMID- 12521061
TI  - PGD training and its impact on general dentist practice patterns.
AB  - This study compares the practice patterns of general dentists with and without
      formal advanced training in AGED or GPR programs. The UCLA School of Dentistry
      surveyed a random selection of dentists from graduating years 1989, 1993, and
      1997 as part of a Health Resources Services Administration (HRSA)-supported
      evaluation of the impact of federal funding on postgraduate general dentistry
      (PGD) programs. Using a sample drawn by the American Dental Association (ADA),
      6,725 dentists were surveyed about their practice, advanced training, patients
      served, and services provided. Of the 2,029 dentists (30 percent) who responded,
      49 percent were practicing dentists with no formal advanced training in general
      dentistry or one of the eight ADA specialties; 7 percent had Advanced Education
      in General Dentistry (AEGD) experience; 20 percent trained in a General Practice
      Residency (GPR); and 24 percent were specialists. Additionally, 7 percent of
      respondents had PGD training and a clinical specialty. GPR-trained dentists were
      significantly more likely to be on a hospital staff and to treat medically
      compromised patients even after ten years of practice. PGD dentists were less
      likely to seek specialty training. Major reasons for seeking PGD training were
      increasing treatment speed, learning to treat medically compromised patients, and
      wanting hospital experience. Primary reasons for not selecting training were
      starting a practice and having a great practice opportunity. Our conclusion is
      that PGD training has an enduring impact on practice patterns and improves access
      to dental care for underserved populations.

PMID- 12521062
TI  - Gender differences in career and practice patterns of PGD-trained dentists.
AB  - This study compares differences by gender in the practice patterns and
      professional activities of general dentists, specialists, and dentists with
      Advanced Education in General Dentistry (AEGD) or General Practice Residency
      (GPR) training. The UCLA School of Dentistry surveyed a random sample of 6,725
      dentists graduating from dental school in 1989, 1993, and 1997 as part of an
      evaluation of the impact of federal funding on postgraduate general dentist (PGD)
      programs. The survey asked about current practice, services referred and
      provided, and professional activities. Of the 2,029 dentists (30 percent) who
      responded, 49 percent were general dentists with no specialty training; 7 percent
      had AEGD training; 20 percent had GPR training; and 24 percent had specialty
      training. General dentists were more likely to be in private practice (p < 0.05).
      AEGDs, specialists, and females were more likely to report faculty positions as a
      secondary occupation. General dentists were more likely to be practice owners
      than AEGD- or GPR-trained dentists. The mean number of patients seen was highest
      for specialists. Females reported fewer patients than males, and this difference
      was significant for GPR-trained dentists. With respect to services, GPR-trained
      dentists reported significantly more biopsy procedures, conscious sedation,
      periodontal surgery, and implants than general dentists. AEGD-trained dentists
      reported more conscious sedation than general dentists. GPR dentists were more
      likely to volunteer time than general dentists without specialty training. PGD
      training appears to result in different types of employment and specific practice
      patterns that strengthen primary care dentistry. We further conclude that there
      are gender differences in the types of practice, patients seen, and services
      provided. These findings occur in addition to training differences.

PMID- 12521063
TI  - Goals, costs, and outcomes of a predoctoral student research program.
AB  - The aims of this work were to describe the goals and costs of a predoctoral
      student research program and compare the career choice and school donations of
      dental alumni who received student research experience to those without the
      experience. The identity of participants in the student research program was
      obtained from college records, and outcomes data on the student researchers from
      the years 1991 to 1994 were obtained with a telephone survey. Survey responses
      were compared to recent alumni surveys of the classes of 1992 and 1994,
      mathematically corrected to provide an estimate for non-research participants. A
      student research program that involves about one-fourth of the class currently
      costs in excess of $100,000. However, the benefits were found to be considerable.
      Compared to the class as a whole, after seven to ten years student researchers
      were 3.5 times more likely to complete specialty training, nearly five times more
      likely to become full-time faculty members, and 32 percent more likely to be
      donors.

PMID- 12521064
TI  - Perspectives on dental education in the Nordic countries.
AB  - The object of this review is to discuss the state of dental education and
      describe current developments at dental schools in the Nordic countries. The main
      focus is the undergraduate dental education; however, the postgraduate system
      will also be addressed. The curriculum model for undergraduate dental education
      in the Nordic countries is based upon the odontological tradition. The influence
      of biomedicine on dental education is increasing at present due to scientific and
      medico-technological developments and the altered disease profiles of oral and
      systemic diseases. These circumstances create new possibilities for dental
      education, but at the same time they raise some problems. In the long-term, the
      strong biomedical influence on dental education will be an advantage to future
      dentists' function and tasks in health care systems in the Nordic countries. In
      the short term, it may result in an identity crisis for dental schools, students,
      and our profession, as we experience the evolution from the traditional
      odontological curriculum model to one significantly influenced by ongoing changes
      in the biomedical field. Continuing professional education and advanced training
      in clinical specialties are likely to play important roles in this evolution.

PMID- 12521065
TI  - Bone scintigraphy as an adjunct for the diagnosis of oral diseases.
AB  - Bone scintigraphy is a very sensitive method for the detection of osteoblastic
      activity of the skeleton. The technique consists of imaging the uptake of bone
      seeking radiopharmaceuticals, particularly technetium-99m labeled diphosphonates,
      in the mineral component of bone, which consists of hydroxyapatite crystals and
      calcium phosphate, as well as in the organic matrix such as collagen fibers.
      Plain radiographs, computed tomography, and magnetic resonance imaging are
      classified as structural imaging modalities, whereas bone scintigraphy is a
      functional method. In many cases, radionuclide imaging techniques are the only
      means by which early physiologic changes that are a direct result of biochemical
      alteration may be assessed, before significant bone mineral changes can be
      detected by other means. Since many oral diseases may cause metabolic changes in
      the oromaxillofacial complex, it would be of great value to use bone scintigraphy
      to evaluate more completely some conditions involving the bones in the region to
      formulate more appropriate treatment plans. Based upon the current literature,
      the authors discuss the possible applications of bone scintigraphy as a
      diagnostic and treatment planning adjunct for oral diseases. Bone scintigraphy
      has proven particularly useful in the study of malignant lesions and in the
      evaluation of vascularized bone grafts used for maxillofacial reconstructions.

PMID- 12521066
TI  - Annual ADEA survey of dental school seniors: 2002 graduating class.

PMID- 12521067
TI  - Forward planning using multileaf collimation as a replacement for patient tissue
      compensation.
AB  - In treatment planning, a dosimetrist may encounter a technique that would best be
      treated by including some type of compensation to correct for tissue or depth
      variations throughout the field, allowing for a more homogeneous dose
      distribution. Recent innovations, such as intensity-modulated radiotherapy
      (IMRT), have been introduced in an effort to address these issues. In many
      institutions, however, the treatment planning capabilities available may not
      accommodate consideration of such new technologies. The treatment planner is
      therefore left to determine how to incorporate these concepts with the current
      technologies available. While compensation may be an option, this may not always
      be possible due to the position of the beam or to actual mechanical restraints.
      Some institutions may also lack the ability and equipment to consider
      compensation at all. The answer is forward planning IMRT. This concept combines
      current forward planning techniques with multiple asymmetrically blocked
      treatment fields, varying the intensity of the beam from a given orientation to
      produce the desired treatment plan.

PMID- 12521068
TI  - The application of dynamic field shaping and dynamic dose rate control in
      conformal rotational treatment of the prostate.
AB  - The current philosophy of dose escalation in the treatment of prostate cancer has
      forced the treatment planner to re-evaluate his/her planning approach. Precise
      and accurate delivery of dose to the prostate while maintaining the required dose
      limits to the normal critical structures, such as the rectum, has become
      increasingly difficult in light of these escalated doses. Conformal treatment
      techniques allow the treatment planner to precisely shape each individual
      treatment field so that desired volume coverage and normal tissue sparing can be
      achieved. In addition to these beam-shaping advantages, adjustment of an
      individual beam's weighting also helps to create the desired distribution and
      tissue sparing. Rotational therapy "simulates" treatment with multiple beams and
      angles, similar to the thought process behind conformal treatment technique. With
      rotational therapy, however, the treatment planner's inability to provide
      adequate beam shaping and weighting adjustment has placed limits on its value as
      a viable planning option. The introduction of computer-controlled treatment
      machines, which allow dynamic adjustment of the field shape with the rotation of
      the beam, makes it possible to re-evaluate rotational therapy as a potential
      option. Similarly, the treatment planner's ability to change field weighting can
      be accomplished by the application of dynamic dose rate control, allowing a
      rotational beam to deliver a weighting similar to that possible with conformal
      fixed-field techniques. Dose-volume histogram data will be used to evaluate doses
      delivered to the prostate, rectum, and bladder using rotational therapy with
      dynamic field shape and dynamic dose rate control as a treatment planning option.
      The dose delivery and normal tissue-sparing potential of this technique compared
      to coplanar and noncoplanar conformal fixed-field techniques will also be
      presented.

PMID- 12521069
TI  - Intensity-modulated photon arc therapy for treatment of pleural mesothelioma.
AB  - Radiotherapy plays a key role in the definitive or adjuvant management of
      patients with mesothelioma of the pleural surface. Many patients are referred for
      radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of
      efficacious doses of radiation to the pleural lining while avoiding lung
      parenchyma toxicity has been a difficult technical challenge. Using opposed
      photon fields produce doses in lung that result in moderate-to-severe pulmonary
      toxicity in 100% of patients treated. Combined photon-electron beam treatment, at
      total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung
      volume receiving over 2100 cGy. We have developed a technique using intensity
      modulated photon arc therapy (IMRT) that significantly improves the dose
      distribution to the pleural surface with concomitant decrease in dose to lung
      parenchyma compared to traditional techniques. IMRT treatment of the pleural
      lining consists of segments of photon arcs that can be intensity modulated with
      varying beam weights and multileaf positions to produce a more uniform
      distribution to the pleural surface, while at the same time reducing the overall
      dose to the lung itself. Computed tomography (CT) simulation is critical for
      precise identification of target volumes as well as critical normal structures
      (lung and heart). Rotational arc trajectories and individual leaf positions and
      weightings are then defined for each CT plane within the patient. This paper will
      describe the proposed rotational IMRT technique and, using simulated isodose
      distributions, show the improved potential for sparing of dose to the critical
      structures of the lung, heart, and spinal cord.

PMID- 12521070
TI  - Heading in the right direction? An innovative approach toward proper patient head
      positioning.
AB  - An in-house-manufactured modification of the standard A-F foam rubber head-neck
      supports (aka. Timo Supports) was designed to eliminate clinical setup problems
      with head immobilization and instability during treatment, thus providing for a
      more comfortable head rest for the patient. The custom design of this head holder
      seeks to eliminate superior-to-inferior shift, and minimize the lateral right-to
      left rotational movement of the head when coupled with an AquaPlast casting
      system. By focusing attention to the seating of the occipital portion of the head
      and contour of the patient's neck, the aforementioned problems of movement were
      addressed, while adhering to the interests of patient comfort in this modified
      head support system.

PMID- 12521071
TI  - The application of electron beam delivery using dose rate variation and dynamic
      couch motion in conformal treatment of the cranial-spinal axis.
AB  - Radiation therapy to the cranial-spinal axis is typically targeted to the spinal
      cord and to the cerebrospinal fluid (CSF) in the subarachnoid space adjacent to
      the spinal cord and brain. Standard techniques employed in the treatment of the
      whole central nervous system do little to compensate for the varying depths of
      spinal cord along the length of the spinal field. Lateral simulation films,
      sagittal magnetic resonance imaging (MRI), or computerized tomography (CT) are
      used to estimate an average prescription depth for treatment along the spine
      field. However, due to the varying depth of the target along the spinal axis,
      even with the use of physical compensators, there can be considerable dose
      inhomogeneity along the spine field. With the advent of treatment machines that
      have full dynamic capabilities, a technique has been devised that will allow for
      more conformal dose distribution along the full length of the spinal field. This
      project simulates this technique utilizing computer-controlled couch motion to
      deliver multiple small electron beams of differing energies and intensities. CT
      planning determines target depth along the entire spine volume. The ability to
      conform dose along the complete length of the treatment field is investigated
      through the application of superpositioning of the fields as energies and
      intensities change. The positioning of each beam is registered with the treatment
      couch dynamic motion. This allows for I setup in the treatment room rather than
      multiple setups for each treatment position, which would have been previously
      required. Dose-volume histograms are utilized to evaluate the dose delivered to
      structures in the beam exit region. This technique will allow for precise
      localization and delivery of a homogeneous dose to the entire CSF space.

PMID- 12521072
TI  - A simple method of alignment for pelvic irradiation in obese patients.
AB  - Administering radiation therapy to obese pelvic patients can pose a difficult
      challenge to even the veteran radiation therapist. Daily reproducibility can be
      achieved with the sacrifice of additional time and filming. We have developed a
      technique which has shown consistent reproducibility of the radiation treatments
      with a minimum of inconvenience to busy schedules.

PMID- 12521073
TI  - Ultrasound imaging for external-beam prostate treatment setup and dosimetric
      verification.
AB  - Ultrasound (US) image-guided patient positional verification was performed daily
      on four prostate cancer patients using the BAT system (NOMOS Corporation, CA).
      The BAT system has shown that the prostate can shift by as much as 1 cm from its
      intended position in any direction. Furthermore, the daily shifts measured by the
      BAT system were included into the treatment planning system to assess changes in
      prostate dose coverage. Dose volume histograms were used to compare the dosimetry
      between the ideal patient set-up situation (prostate always positioned correctly)
      and that taking all patient daily shifts into consideration. Daily patient shifts
      on the order of magnitudes measured, can significantly and adversely affect
      dosimetric coverage, therefore an US-based patient positioning system is required
      for improving the therapeutic ratio.

PMID- 12521074
TI  - Dose calculation errors due to inaccurate representation of heterogeneity
      correction obtained from computerized tomography.
AB  - Computerized tomography (CT) is used routinely in evaluating radiation therapy
      isodose plans. With the introduction of 3D algorithms such as the voxel raytrace,
      which determines inhomogeneity corrections from actual CT Hounsfield numbers,
      caution must be used when evaluating isodose calculations. Artifacts from
      contrast media and dental work, radiopaque markers placed by the treatment
      planner, and changing bowel and rectal air patterns all have the potential to
      introduce error into the calculation due to inaccurate assessment of high or low
      density. Radiopaque makers such as x-spot BB's or solder wire are placed
      externally on the patient. Barium contrast media introduced at the time of
      simulation may be necessary to visualize specific anatomical structures on the CT
      images. While these localization and visualization tools may be necessary, it is
      important to understand the effects they may introduce in the planning process.
      Other problems encountered are patient specific and out of the control of the
      treatment planner. These include high- and low-density streaking caused by dental
      work, which produce computational errors due to overestimation, and small bowel
      and rectal air, the patterns of which change on a daily basis and may result in
      underestimation of structure density. It is important for each treatment planner
      to have an understanding of how this potentially tainted CT information may be
      applied in dose calculations and the possible effects they may have. At our
      institution, the voxel raytrace calculation is automatically forced any time
      couch angle is introduced. Errors in the calculation from the above mentioned
      situations may be introduced if a heterogeneity correction is applied. Examples
      of potential calculation errors and the magnitude of each will be discussed. The
      methods used to minimize these errors and the possible solutions will also be
      evaluated.

PMID- 12521075
TI  - Design, fabrication, and testing of a fiduciary tray to be used with the
      multileaf intensity-modulating collimator for portal film localization.
AB  - The purpose of this study was to design, fabricate, and test a fiduciary tray to
      be used for portal film localization using the multileaf intensity-modulating
      collimator (MIMiC) developed by NOMOS Corporation of Sewickley, PA. The MIMiC is
      a tertiary collimator that is utilized in intensity-modulated radiation therapy
      (IMRT) treatments. At this time, no MIMiC fiduciary tray exists for commercial
      use. Due to the escalation of dose in IMRT treatments, the need for accurate
      localization is of utmost importance. A slight error in interpretation could lead
      to significant errors in dosimetric coverage of the target volume and possible
      overdosing of normal tissues. A fiduciary tray that fits onto the MIMiC was
      designed. Special attention was given to ensure that treatment could not be
      accidentally given with the tray in place. Various localization tests were
      administered to ensure accuracy for brain and pelvic treatments. The fiduciary
      tray should directly impact the daily operations for not only the radiation
      therapists but also the radiation oncologists by aiding in the direct comparison
      of setup films to weekly port films.

PMID- 12521076
TI  - Evaluation of post-plan dosimetry using TRUS and CT after transperineal prostate
      seed implant.
AB  - The purpose of this study was to evaluate the variability in dosimetry due to the
      change in prostate volume for permanent transperineal brachytherapy seed implant.
      This research is the beginning of an in-house quality assessment program.
      Nineteen cases were retrospectively evaluated. A single physician defined
      prostate volumes in all cases. Group A consisted of 3 cases that were treated
      with external-beam radiation therapy (EBRT) to 4500 cGy, followed by a
      brachytherapy implant boost of 10,800 cGy. Group B included 16 cases that were
      implant only, prescribed to 14,400 cGy. Prostate images were acquired before seed
      implant using transrectal ultrasound (TRUS), immediately following seed implant
      using TRUS, and by computed tomography (CT) acquired several weeks postimplant.
      The prostate images were digitized into a commercial treatment planning system
      for planning purposes and dosimetric evaluation for the 3 procedures. Prostate
      volumes were calculated by the treatment planning system. Additional data
      collected included the percentage of prostate receiving the prescribed dose and
      dose to 90% and 80% of the prostate. The dose delivered to V150 was also
      recorded. Overall, the postimplant ultrasound plan showed similar coverage to the
      ultrasound preplan, while the CT postplan revealed less than expected dosimetric
      coverage. The postplan CT results prompted us to evaluate our scheduling process,
      as well as prostate definition using TRUS and CT.

PMID- 12521077
TI  - TLD linearity vs. beam energy and modality.
AB  - Thermoluminescent dosimetry (TLD) is considered to be a valuable dosimetric tool
      in determining patient dose. Lithium fluoride doped with magnesium and titanium
      (TLD-100) is widely used, as it does not display widely divergent energy
      dependence. For many years, we have known that TLD-100 shows supralinearity to
      dose. In a radiotherapy clinic, there are multiple energies and modality beams.
      This work investigates whether individual linearity corrections must be used for
      each beam or whether a single correction can be applied to all beams. The
      response of TLD as a function of dose was measured from 25 cGy to 1000 cGy on
      both electrons and photons from 6 to 18 MeV. This work shows that, within our
      measurement uncertainty, TLD-100 exhibits supralinearity at all megavoltage
      energies and modalities.

PMID- 12521078
TI  - Immunotherapy: an alternative for bone marrow transplantation (BMT) in severe
      acquired aplastic anemia?

PMID- 12521079
TI  - Strokes in adolescents and young adults.

PMID- 12521080
TI  - Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) with
      methylprednisone and oxymethalone in aplastic anaemia.
AB  - From 1986 to 1994 we treated 26 patients of aplastic anaemia between 6 to 61
      years age group with ATG/ALG, Methylprednisone and Oxymethalone. Five had very
      severe aplastic anaemia, 16 had severe and 5 nonsevere disease. Disease was
      associated with hepatitis in 5 patients and with pregnancy and drug use in 2
      patients each. In others no cause could be ascertained. A total of 31 courses of
      treatment were given (range 1-3 courses per patient). Nine patients had complete
      response (34.62%) and 3 had partial response (11.54%) with an overall response
      rate of 46.16%. Four patients died within 2 months of starting the treatment. The
      median follow up was 24 months (range 6-102 months) with an overall survival
      probality of 45% at 2 yr. At the time of evaluation 12 patients have died, 9 are
      alive disease-free and 5 are alive with disease. The side effects associated with
      therapy were tolerable and did not require cessation of therapy in any patient.
      We conclude that ATG/ALG with Methylprednisone and Oxymethalone is beneficial to
      significant number of patients with aplastic anaemia.

PMID- 12521081
TI  - Non-traumatic coma--profile and prognosis.
AB  - Two hundred consecutive patients of non-traumatic coma, were investigated to
      establish its aetiology. Neurologic profile of these patients included assessment
      of Glasgow Coma Scale (GCS) score and evaluation of brainstem reflexes. 102
      patients died and only 54 patients could make good recovery. Cerebrovascular
      diseases (33%), CNS infections (21%), and hepatic encephalopathy (18%) were the
      frequent causes of non-traumatic coma, with the first two carrying relatively
      poor prognosis. Poor outcome was also associated with low GCS score and absence
      of brainstem reflexes specially absent pupillary, oculocephalic and
      oculovestibular responses and decerebrate posture.

PMID- 12521082
TI  - Clinical dysautonomia in diabetes mellitus--a study with seven autonomic reflex
      function tests.
AB  - Thirty-eight patients of NIDDM, 12 of IDDM and 10 healthy age matched controls
      were subjected to seven standardised autonomic reflex function tests. A scoring
      criteria was utilised for diagnosing and grading the severity of dysautonomia.
      Eight patients of IDDM and 24 of NIDDM had dysautonomia. One-third of the
      patients in each group had grade IV autonomic dysfunction. Severity of autonomic
      dysfunction was directly related to the duration of disease in NIDDM whereas in
      IDDM this relation was not seen. Peripheral neuropathy was almost always
      associated with dysautonomia in NIDDM. On the contrary, in IDDM dysautonomia was
      independent of peripheral neuropathy. Charcot's arthopathy, dysphagia,
      constipation and nocturnal diarrhea were always associated with evidence of
      dysautonomia. Other symptoms viz. gustatory sweating, postural dizziness and
      impotence did not necessarily indicate dysautonomia.

PMID- 12521083
TI  - Cholesterol lipoproteins, triglycerides, rural-urban differences and prevalence
      of dyslipidaemia among males in Rajasthan.
AB  - To develop profiles of serum cholesterol lipoproteins and triglycerides,
      influence of rural versus urban lifestyle in their levels and prevalence of
      dyslipidaemias, we studied cohorts of male population in Rajasthan. Fasting blood
      samples were obtained from 401 men (age range 20-73 years) randomly selected from
      a larger sample of 3397 during a comprehensive cardiovascular risk factor survey
      in rural (202 men) and urban (199 men) populations. Serum total cholesterol, low
      density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol
      and triglycerides (TG) were determined and correlated with age and anthropometric
      variables. The lipid levels were classified according to US National Cholesterol
      Education Program (NCEP) guidelines. The mean +/- SD levels in mg/dl were, total
      cholesterol 170.5 +/- 40, LDL cholesterol 102.1 +/- 36, HDL cholesterol 43.6 +/-
      12 and TG 124.0 +/- 50. The mean levels in rural vs. urban population were total
      cholesterol 165 +/- 37 vs. 176 +/- 43 (p = 0.008), LDL cholesterol 97 +/- 33 vs.
      108 +/- 39 (p = 0.003), HDL cholesterol 44 +/- 13 vs. 43 +/- 12 (p = 0.44) and TG
      122 +/- 46 vs 126 +/- 55 (p = 0.41). There was significant positive correlation
      of age and body-mass index with total and LDL cholesterol and triglycerides but
      not with HDL cholesterol. When classified according to the NCEP guidelines high
      total cholesterol (> or = 240 mg/dl) and LDL cholesterol (> or = 160 mg/dl) was
      in 33 (8.3%). Borderline high total cholesterol (200-239) was in 64 (16%) and
      borderline high LDL cholesterol (130-159) in 55 (13.7%). Borderline high
      triglyceride (200-400 mg/dl) was in 33 (8.2%) and severe hypertriglyceridaemia in
      none. Low HDL cholesterol (< 35 mg/dl) was in 96 (23.9%) and protective level of
      HDL cholesterol (> or = 60 mg/dl) in 47 (11.7%). In urban as compared to rural
      men the prevalence of hypercholesterolaemia > 200 mg/dl (28% vs 22%) and hyper
      LDL cholesterolaemia (26% vs 18%) were significantly more.

PMID- 12521084
TI  - Detection of antibodies to HIV-1 in serum and saliva.
AB  - In this study we report the detection of antibodies to HIV-1 in paired serum and
      saliva collected from 118 HIV-1 infected patients and 80 normal controls in
      Madras, South India. Saliva was collected using Omnisal (R) collection device.
      All the reactive samples were confirmed by Western blot test (WB), while all the
      control serum and saliva were negative for HIV-1 antibodies. 107 (90.6%) HIV
      individual's serum and saliva contained antibodies to HIV-1. When these reactive
      samples were tested by WB test for confirmation the following results were
      obtained; 68% HIV individuals' paired serum and saliva were positive; while 9% of
      serum samples were positive and the saliva specimens were negative on WB. 3% of
      paired samples showed indeterminate Western blot pattern in contrast to 10% of
      serum showed full WB pattern while the saliva result was indeterminate. It is
      suggested that saliva testing may be appropriate for surveillance and
      epidemiological studies. However, if used for individual HIV diagnosis it is
      imperative to use a confirmatory test.

PMID- 12521085
TI  - Role of fibronectin in diagnosis of malignant ascites.
AB  - The aim of the study was to evaluate the role of ascitic fluid fibronectin in the
      diagnosis of malignant ascites. Fibronectin is a glycoprotein which plays an
      important role in regulating the organisation of the cell cytoskeleton and cell
      morphology. Ascitic fluid samples from 35 patients, 20 with portal hypertension
      (Group-I) and 15 with malignant ascites (Group-II) were analysed for proteins,
      cell counts, fibronectin levels and malignant cell cytology. Mean ascitic fluid
      fibronectin level was found to be significantly higher in malignant ascites as
      compared to portal hypertension (p < 0.001). At a cut off value of 94.67
      microg/ml, the sensitivity, specificity, positive accuracy, negative accuracy and
      overall diagnostic accuracy was found to be 100%, 95%, 93.8%, 100% and 97.1%
      respectively.

PMID- 12521086
TI  - Cholelithiasis in sickle cell disease in India.
AB  - Eighty cases (63 Males and 17 Females) of sickle cell disease were searched for
      gall stone by ultrasonography, 8 (10%) cases had gall stone. Gall stones were
      more common in males (11.1%) than females (5.8%). It was not found below 13 years
      of age. Three cases had single and five cases had multiple gall stones. Three of
      them had thickened gall bladder wall. Typical biliary colic was uncommon (1
      case). There was no case of obstructive jaundice. HbF% level was significantly
      lower in cases with gall stone (12.31 +/- 3.95) than without gall stones (16.73
      +/- 6.30). Episodes of aggravated anaemia and total serum bilirubin was
      significantly higher (1.27/pt and 4.12 +/- 1.34 mg%) in cases with gall stone
      than without gall stone (0.31/pt and 2.74 +/- 1.47 mg%). The above findings
      suggest association of greater degree of haemolysis with formation of gall stone
      in sickle cell disease cases.

PMID- 12521087
TI  - Multifocal motor neuropathy.
AB  - A brief report of four patients with Multifocal Motor Neuropathy (MMN) two of
      whom improved with cyclophosphamide is presented. This is the first report of MMN
      from India.

PMID- 12521088
TI  - Pulmonary eosinophilia.

PMID- 12521089
TI  - Helicobacter pylori: current status.

PMID- 12521090
TI  - Prevention and treatment of coronary artery disease.

PMID- 12521091
TI  - Radiculopathy as presenting manifestation of primary CNS lymphoma.

PMID- 12521092
TI  - Subarachnoid haemorrhage resulting from rhinocerebral mucormycosis.

PMID- 12521093
TI  - Secondary narcolepsy in a case of multiple sclerosis.

PMID- 12521094
TI  - Intrahepatic calculi in sickle cell anaemia.

PMID- 12521095
TI  - Protein S deficiency in brain infarction of unknown cause.

PMID- 12521096
TI  - Female hemophilia.

PMID- 12521097
TI  - Rabies after mongoose bite.

PMID- 12521098
TI  - Lupus anticoagulant presenting as a stroke in young.

PMID- 12521100
TI  - Hashimoto's thyroiditis with ophthalmopathy and dermopathy.

PMID- 12521099
TI  - Carcinomatous meningitis in a case of ovarian carcinoma.

PMID- 12521101
TI  - Missing jig saw puzzle piece in coarctation of inferior vena cava.

PMID- 12521102
TI  - Evaluation of two treatment regimens of pralidoxime.

PMID- 12521103
TI  - Signed referee's comments.

PMID- 12521104
TI  - Metals in bulk deposition and surface waters at two upland locations in northern
      England.
AB  - Concentrations of aluminium and minor metals (Mn, Ni, Cu, Zn, Sr, Cd, Ba, Pb)
      were measured in precipitation and surface water at two upland locations (Upper
      Duddon Valley, UDV; Great Dun Fell, GDF) in northern England for 1 year
      commencing April 1998. At both locations, the loads in bulk precipitation were at
      the lower ends of ranges reported for other rural and remote sites, for the
      period 1985-1995. The deposited metals were mostly in the dissolved form, and
      their concentrations tended to be greatest when rainfall volumes were low. The
      concentrations of Cu, Zn and Pb in deposition were correlated (r2 > or = 0.40)
      with concentrations of non-marine sulphate. Three streams, ranging in mean pH
      from 5.07 to 7.07, and with mean concentrations of dissolved organic carbon (DOC)
      < 1 mg l(-1). were monitored at UDV, and two pools (mean pH 4.89 and 6.83, mean
      DOC 22 and 15 mg l(-1)) at GDF. Aluminium and the minor metals were mainly in the
      dissolved form, and in the following ranges (means of 49-51 samples. microg l(
      1)): Al 36-530. Mn 4.4-36, Ni 0.26-2.8, Cu 0.25-1.7, Zn 2.1-30, Cd 0.03-0.16, Ba
      1.9-140, Pb 0.10-4.5. Concentrations were generally higher at GDF. Differences in
      metal concentrations between the two locations and between waters at each
      location, and temporal variations in individual waters, can be explained
      qualitatively in terms of sorption to solid-phase soil organic matter and mineral
      surfaces, complexation and transport by DOC, and chemical weathering. The UDV
      catchments are sinks for Pb and sources of Al, Mn, Sr, Cd and Ba. The GDF
      catchments are sources of Al, Mn, Ni, Zn, Sr, Cd and Ba. Other metals measured at
      the two locations are approximately in balance. Comparison of metal:silicon
      ratios in the surface waters with values for silicate rocks indicates enrichment
      of Ni and Cu, and substantial enrichment of Zn, Cd and Pb. These enrichments,
      together with high metal deposition in the past, make it likely that
      concentrations of the metals in the surface waters are governed by release from
      catchment pools of atmospherically-deposited metal. The catchments appear to be
      responding on a time scale of decades, possibly centuries, to changes in metal
      deposition. For the more acid waters at UDV, the calculated free-ion
      concentrations of Al are similar to published LC50 values for acute toxicity
      towards fish. The free-ion concentrations of Ni, Cu, Zn and Cd in all the surface
      waters are one-to-four orders of magnitude lower than reported LC50 values for
      fish.

PMID- 12521105
TI  - Macrobenthic community in the Douro estuary: relations with trace metals and
      natural sediment characteristics.
AB  - The relationship between macrobenthic community structure and natural
      characteristics of sediment and trace metal contamination were studied in the
      lower Douro estuary (Portugal, NW, Iberian Peninsula), using an innovative
      threefold approach (SQG, Sediment Quality Guidelines), metal normalization to Fe,
      and macrobenthic community structure. This study allowed detection of a clear
      signature of anthropogenic contamination, in terms of Zn, Cu, Pb, and Cr in the
      north bank of the estuary, which experiences high urban pressure. Using the SQG
      approach, metal concentrations above ERM (effects range-median) were observed
      only at one sampling station, but several stations had levels above ERL (effects
      range-low). The macrobenthic community had a low diversity, with only 19 species
      found in the entire estuarine area, dominated by opportunistic species. The
      granulometric distribution of the sediments (estimated from the combination of
      organic matter, Fe and Al) seemed to be the major structuring factor for the
      communities, establishing the natural macrobenthic distribution pattern. The
      metals (Zn, Cu, Pb, and Cr) seemed to act as a disturbing factor over the natural
      distribution, with deleterious consequences for the macrobenthic communities.

PMID- 12521106
TI  - Biofiltration of gasoline vapor by compost media.
AB  - Gasoline vapor was treated using a compost biofilter operated in upflow mode over
      4 months. The gas velocity was 6 m/h, yielding an empty bed retention time (EBRT)
      of 10 min. Benzene, toluene, ethylbenzene and xylene (BTEX) and total petroleum
      hydrocarbon (TPH) removal efficiencies remained fairly stable approximately 15
      days after biofilter start-up. The average removal efficiencies of TPH and BTEX
      were 80 and 85%, respectively, during 4 months of stable operation.
      Biodegradation portions of the treated TPH and BTEX were 60 and 64%,
      respectively. When the influent concentration of TPH was less than 7800 mg
      TPH/m3, approximately 50% of TPH in the gas stream was removed in the lower half
      of the biofilter. When the influent concentration of BTEX was less than 720 mg
      BTEX/m3, over 75% of BTEX in the gas stream was removed in the lower half of the
      biofilter. Benzene removal efficiency was the lowest among BTEX. A pressure drop
      could not be detected over a 1-m bed height at a gas velocity of 6 m/h after
      approximately 4 months of operation. Results demonstrated that BTEX in gasoline
      vapor could be treated effectively using a compost biofilter.

PMID- 12521107
TI  - Physiological and biochemical responses of two cultivars of wheat to elevated
      levels of CO2 and SO2, singly and in combination.
AB  - In view of the present increasing trends of anthropogenic emissions of carbon
      dioxide (CO2) and sulphur dioxide (SO2) throughout the world, the present study
      was aimed at investigating the long-term influence of elevated concentrations of
      CO2 and SO2, singly and in combination on the physiological and biochemical
      characteristics of two cultivars of wheat (Triticum aestivum L. cv. Malviya 234
      and HP1209). For this purpose, the plants were grown in open top chambers under
      field conditions and were fumigated with 600 ppm CO2, 0.06 ppm SO2 and 600 ppm
      CO2 + 0.06 ppm SO2 separately for 8 h daily (0800-1600 h) from germination to
      grain maturity. The individual treatment of SO2 advers#ely affected both the
      cultivars of wheat by reducing protein and starch contents. The respiration rate,
      total soluble sugars and total phenolics, however, increased in response to SO2.
      Stimulation of photosynthesis rate and reduction in stomatal conductance and
      transpiration rate were observed under CO2 treatment. Concentrations of total
      soluble sugars, starch and total phenolics increased in response to CO2 and CO2 +
      SO2 treatments. In combined treatment, CO2 modified the plant response to SO2 in
      both the cultivars. Elevated CO2 increased the photosynthesis rate under combined
      treatment. Higher levels of starch and soluble sugars under combined treatment
      provided extra carbon for SO2 detoxification. The pattern of intraspecific
      response of wheat to different treatments was more or less similar, but the
      magnitude of response differed significantly.

PMID- 12521108
TI  - Determination of beta-adrenergic receptor blocking pharmaceuticals in United
      States wastewater effluent.
AB  - Beta adrenergic receptor antagonists (beta-Blockers) are frequently prescribed
      medications in the United States and have been identified in European municipal
      wastewater effluent, however no studies to date have investigated these compounds
      in United States wastewater effluent. Municipal wastewater effluent was collected
      from treatment facilities in Mississippi, Texas, and New York to investigate the
      occurrence of metoprolol, nadolol, and propranolol. Propranolol was identified in
      all wastewater samples analyzed (n = 34) at concentrations < or = 1.9 microg/l.
      Metoprolol and nadolol were identified in > or = 71% of the samples with
      concentrations of metoprolol < or = 1.2 microg/l and nadolol < or = 0.36
      microg/l. Time course studies at both Mississippi plants and the Texas plant
      indicate that concentrations of propranolol, metoprolol, and nadolol remain
      relatively constant at each sampling period. This study indicates that beta
      Blockers are present in United States wastewater effluent in the ng/l to microg/l
      range.

PMID- 12521109
TI  - Reproductive success and chlorinated hydrocarbon contamination of resident great
      blue herons (Ardea herodias) from coastal British Columbia, Canada, 1977 to 2000.
AB  - Over the period 1977-2000, eggs of Pacific great blue heron (Ardea herodias
      fannini) were collected from 23 colonies along the southern coast of British
      Columbia, Canada, and analyzed for persistent organochlorine (OC) pesticides and
      polychlorinated biphenyls (PCBs). Concentrations of OC pesticides in eggs
      declined sharply in the late 1970s, after which there were minimal changes. The
      sums of PCB congeners were not reduced appreciably during the 1980s and 1990s,
      but Aroclor 1260 concentrations suggested a sharp decline in PCB contamination of
      eggs in the late 1970s, similar to that shown for OC pesticides. Eggs collected
      along or near the Fraser River delta showed higher levels of most pesticides
      compared to other monitored colonies. Although the delta lands support a long
      standing agricultural economy, the primary factors influencing OC levels in the
      delta colonies were thought to be driven by estuarine processes. We suggest two
      possible influencing factors were: 1) a greater rate of bioaccumulation in the
      estuary due to the deposition of particulates collected over a vast area
      encompassed by the Fraser River watershed; or 2) a higher rate of
      biomagnification in the estuary due to species differences at lower trophic
      levels of the heron food chain. Eggs from urban colonies contained higher levels
      of PCBs. The congener pattern was not clearly different from that observed in
      less contaminated eggs from rural and pulp mill-influenced colonies, except that
      colonies in Vancouver had greater proportions of PCB-66, suggesting a local
      source of Aroclor 1242. Productivity in the coastal heron colonies was highly
      variable over the period of study, with 71% of recorded colony-wide reproductive
      failures occurring in colonies near pulp mills. However, the predominant factors
      influencing reproductive success were probably disturbance by humans and bald
      eagles, combined with loss and degradation of nesting habitat, and not sublethal
      toxicity.

PMID- 12521110
TI  - Lead in grain size fractions of road-deposited sediment.
AB  - Road-deposited sediment (RDS) is an important environmental medium for assessing
      contaminant levels in urban systems. Their atmospheric resuspension has
      significant implications for human health, and storm water transport can directly
      impact aquatic biota. Data from 20 RDS samples from Palolo Valley, Oahu, Hawaii,
      were fractionated into six grain-size classes and analyzed for Pb using a weak
      HCl (0.5 M) digestion. Data indicate significant Pb contamination in all samples.
      Median labile Pb concentration (n = 120) was 170 mg/kg, with a range from 4 to
      1750 mg/kg. The five sediment fractions < 1000 microm had statistically similar
      Pb concentrations, but all were significantly greater than the coarsest fraction
      examined (1000-2000 microm). Silt plus clay ( < 63 microm) was the single most
      important mass component with 38% of the total sediment stored in this fraction.
      Mass of sediment < 63 microm combined with a median labile Pb concentration of
      222 mg/kg accounted for 51% of the total Pb load stored in road sediments. These
      findings are significant from an environmental management perspective, and these
      issues are discussed in light of street sweeper sediment grain size removal
      efficiencies.

PMID- 12521111
TI  - Levels and patterns of persistent organochlorines in minke whale (Balaenoptera
      acutorostrata) stocks from the North Atlantic and European Arctic.
AB  - Regional variation in PCBs and organochlorine (OC) pesticide concentrations was
      examined using the blubber of 155 minke whales (Balaenoptera acutorostrata)
      sampled in seven regions in the North Atlantic and European Arctic, including
      western and southeastern Greenland, the Norwegian Sea, the North Sea and the
      Barents Sea. The levels and relative proportions of OCs were also used to examine
      the boundaries for North Atlantic minke whale stocks previously defined by the
      International Whaling Commission (IWC). Concentrations of major OC groups
      (sigmaPCB, 89.1-22 800 ng/g lipid; sigmaDDT, 65.3-6280 ng/g lipid; sigmaCHL, 33.3
      2110 ng/g lipid) generally increased from west to east, while HCH concentrations
      (sigmaHCH, < 1-497 ng/g lipid) showed the opposite trend. Statistical comparison
      between six regions using sex-adjusted least squared mean concentrations showed
      that minke whales from the Barents Sea had significantly higher concentrations of
      EPCBs than those from the Vestfjorden/Lofoten, the North Sea, and west Svalbard,
      as well as significantly higher sigmaDDT concentrations compared to west
      Greenland animals. The differences in concentrations suggest that west and
      southeast Greenland minkes may represent one group of whales, which are distinct
      from both the Jan Mayen minkes and those from other IWC defined stocks in
      northern European waters. Principal components analysis using proportions of 71
      PCB congeners and 20 OC pesticides (of total OCs) did not reveal any major
      differences among groups although minkes from the North Sea were distinguished
      from those from Greenland waters by higher loadings of more highly chlorinated
      PCBs and recalcitrant OC pesticides. The general similarity in mean levels of
      sigmaPCBs, sigmaDDT and sigmaCHL, as well as mean principal components analysis
      scores, among minkes sampled at Jan Mayen, Svalbard, Vestfjorden/Lofoten, the
      North Sea and the Barents Sea suggests that the whales are quite mobile and may
      feed in multiple areas within the northeastern Atlantic.

PMID- 12521112
TI  - Mayfly larvae (Baetis rhodani and B. vernus) as biomonitors of trace metal
      pollution in streams of a catchment draining a zinc and lead mining area of Upper
      Silesia, Poland.
AB  - Larvae of two Baetis species were used to investigate spatial and temporal
      variability in the bioavailabilities of cadmium, copper, lead, zinc and iron in
      the river Biala Przemsza and its tributaries draining an area of lead and zinc
      mining in Upper Silesia, Poland. Accumulated metal concentrations were measured
      in April, May, August and November 2000. Both species indicated significant local
      geographical variability in availabilities of zinc, iron, lead and cadmium, but
      not copper. Accumulated concentrations of lead, zinc and cadmium confirmed the
      high general contamination of the Biala Przemsza system by these three trace
      metals. Larvae showed little seasonal variation in concentrations of cadmium,
      copper, lead and iron. Accumulated zinc concentrations were low in Baetis rhodani
      in August, perhaps as a result of insufficient time for high concentrations to
      accumulate since hatching of the larvae. Samples collected in August most nearly
      matched criteria of the greatest availability of larvae for collection and their
      size homogeneity, minimising the possibilities of any effect of differential
      larval size and/or age on accumulated metal concentrations. Mayfly larvae are
      members of a suite of potential stream biomonitors in Central Europe, which
      together can provide information on the different sources of bioavailable trace
      metals present in aquatic ecosystems.

PMID- 12521113
TI  - Distribution of polycyclic aromatic hydrocarbons in water and surface sediments
      from Daya Bay, China.
AB  - Marine culture is thriving in China and represents a major component of the
      regional economy in coastal zones, yet the environmental quality of many of those
      areas has never been studied. This paper attempts to investigate the quality
      status of Daya Bay, a key aquaculture area in China. The levels of 16 polycyclic
      aromatic hydrocarbons (PAHs) were determined in water and sediment samples of the
      bay. The total concentrations of 16 PAHs varied from 4228 to 29325 ng l(-1) in
      water, and from 115 to 1134 ng g(-1) dry weight in sediments. In comparison to
      many other marine systems studied, the PAH levels in Daya Bay waters were
      relatively high, and at six sites they were sufficiently high (> 10 microg l (
      1)) to cause acute toxicity. The PAH composition pattern in sediments suggest
      dominance by medium to high molecular weight compounds, and the ratio of certain
      related PAHs indicate important pyrolytic and petrogenic sources. Further
      analysis showed that the distribution coefficient (KD) increased with the
      particular organic carbon content of sediments, consistent with the PAH partition
      theory. The organic carbon normalised distribution coefficient (K(oc)) also
      increased with the compounds' octanol/water partition coefficient (K(ow)),
      confirming the potential applicability of the linear free energy relationships in
      the modelling and prediction of PAH behaviour in marine environments.

PMID- 12521114
TI  - Metal behaviour in an estuary polluted by acid mine drainage: the role of
      particulate matter.
AB  - The concentrations of dissolved and suspended particulate Cd, Cu and Zn have been
      determined in water samples obtained during two axial transects of the Rio Tinto
      Huelva Ria system in south-west Spain, which is severely impacted by acid mine
      drainage. Although the metal concentrations in both phases were elevated,
      dissolved metals were dominant and, in the upper estuary, constituted > 99% of
      total metal in the water column. Dissolved metals behaved non-conservatively on
      each transect, with maximum concentrations in the low salinity region. There was
      no evidence of metal adsorption within the turbidity maximum zone, despite the
      high specific surface areas of resuspending particles. Measurements of
      electrophoretic mobility showed that the suspended particulate matter (SPM) had a
      positive surface charge in the salinity range 0-4, where the waters had a pH < 3.
      Desorption experiments were carried out in which SPM from the turbidity maximum
      zone was resuspended in coastal seawater. The desorption of the metals was
      monitored for 24 h, using anodic stripping voltammetry (ASV) to detect the
      variation in total dissolved Cd, Cu and Zn and the species of Cu and Zn. Total
      dissolved Cd concentrations doubled during the incubation period, whereas the
      concentration of total dissolved Cu declined and that of Zn remained rather
      constant. The ASV-labile fraction of dissolved Cu and Zn showed an initial sharp
      release followed by a slower uptake. However, desorption was shown to be a minor
      source of dissolved metals and made little contribution to the non-conservative
      behaviour in the low salinity zone. The results are used to predict the effects
      of acid mine drainage on estuarine ecology.

PMID- 12521115
TI  - Polychlorinated camphenes (toxaphenes), polybrominated diphenylethers and other
      halogenated organic pollutants in glaucous gull (Larus hyperboreus) from Svalbard
      and Bjornoya (Bear Island).
AB  - The levels of polychlorinated camphenes (toxaphenes) were investigated in liver
      samples from 18 glaucous gulls (Larus hyperboreus) from Bjornoya (74 degrees N,
      19 degrees E) and four individuals from Longyearbyen (78 degrees N, 15 degrees
      E). Additionally brominated flame retardants (BFRs), PCBs and chlorinated
      pesticides were investigated in liver and intestinal contents of 15 of the
      glaucous gulls from Bjornoya. Of the analysed BFRs only 2,2',4,4'-tetra- and
      2,2',4,4',5-pentabrominated diphenylethers (PBDE 47 and 99) could be detected.
      The concentrations ranged between 2 and 25 ng/g ww. In addition, high resolution
      measurements with GC/HRMS revealed the existence of several, not quantified,
      PBDEs and polybrominated biphenyls (PBBs) congeners in the samples. B9-1679 and
      B8-1413 were the dominating toxaphenes with median concentrations of 8 and 15
      ng/g ww. Concentrations of toxaphenes and PBDEs were up to 100-times lower than
      the concentrations of PCB and some of the pesticides. PCB and p,p/-DDE
      constituted 90% of the contaminants found.

PMID- 12521116
TI  - Temporal variations in atmospheric CO2 concentrations in Kuwait City, Kuwait with
      comparisons to Phoenix, Arizona, USA.
AB  - Hourly atmospheric carbon dioxide (CO2) concentration measurements are available
      from 1996 to present for a suburban site within the growing metropolitan area of
      Kuwait City. Analyses of this record reveal (a) an annual cycle with highest
      values in February and lowest values in September reflecting the growth and decay
      of vegetation in the Northern Hemisphere as well as fluctuations in motor
      traffic, (b) a weekly cycle with highest values during the weekdays and lowest
      values during weekends, and (c) a diurnal cycle with highest values after sunset
      when the local atmosphere becomes more stable following vehicular emission of CO2
      throughout the day and lowest values in late afternoon following several hours of
      relatively unstable conditions. During the daytime, CO2 concentrations are
      related to wind direction, with westerly winds (coming from the desert) promoting
      lowest CO2 concentrations. At night, lowest CO2 levels are associated with higher
      wind speeds and winds from the north. The findings from the Kuwait City area,
      particularly when contrasted with the situation in Phoenix, further our
      understanding of the dynamics of CO2 levels in urban environments.

PMID- 12521117
TI  - Evaluation of internal transcribed spacer region of ribosomal DNA sequence
      analysis for molecular characterization of Candida albicans and Candida
      dubliniensis isolates from HIV-infected patients.
AB  - Molecular typing systems have been needed to study Candida colonization in HIV
      infected patients, particularly for investigating virulence and fluconazole
      resistance. Three methods--electrophoretic karyotyping (EK), detection of
      restriction fragment length polymorphisms (RFLP) and randomly amplified
      polymorphic DNA analysis (RAPD)--have been most frequently used. In this study,
      comparative sequence analysis of the internal transcribed spacer (ITS) region of
      rDNA was evaluated for delineation of Candida isolates from 14 HIV-infected
      patients. EK, ITS sequence analysis, RFLP and RAPD resulted in 11, 10, 9 and 8
      DNA genotypes, respectively, from 39 Candida albicans isolates. The 10 genotypes
      observed using ITS sequence analysis were defined by six variation sites in the
      sequence. Molecular typing of sequential oral isolates showed the persistence of
      the same genotype of C. albicans in nine patients, and genotype variation in one
      patient. EK and RAPD showed that another patient was co-infected by two distinct
      genotypes and ITS analysis identified one of the two genotypes as Candida
      dubliniensis. Comparative ITS sequence analysis is a quick and reproducible
      method that provides clear and objective results, and it also identifies C.
      dubliniensis. The discriminatory power of this new typing approach could be
      improved by concomitant analysis of other DNA polymorphic sequences.

PMID- 12521118
TI  - Molecular diversity, new species and antifungal susceptibilities in the Exophiala
      spinifera clade.
AB  - Black yeasts morphologically identified as Exophiala cf. spinifera were re
      analyzed on the basis of morphology, nutritional physiology and ITS rDNA
      sequencing data. Ribosomal small subunit (SSU) DNA sequence data confirmed that
      strains belonged to a clade containing the ex-type strain of E. spinifera.
      Variation in the Internal Transcribed Spacer (ITS) region of the rDNA was studied
      within this group. Five infraspecific groups were delineated. Phylogenetic
      analysis of the SSU rDNA data revealed that several of the strains analyzed were
      located at considerable evolutionary distance from the E. spinifera clade. ITS
      rDNA sequencing showed that the deviating strains could not be identified with
      any existing species. Two new species, E. attenuata and E. nishimurae, were
      therefore proposed. Antimycotic susceptibility data of the new species were
      compared with those obtained with members of the E spinifera clade.

PMID- 12521119
TI  - Relative contributions of myeloperoxidase and NADPH-oxidase to the early host
      defense against pulmonary infections with Candida albicans and Aspergillus
      fumigatus.
AB  - Generation of oxidative products by phagocytic cells is known to be an important
      host defense mechanism directed toward killing of invading microorganisms. The
      importance of two major oxidant-producing enzymes, myeloperoxidase (MPO) and
      NADPH-oxidase, in in vivo fungicidal action was directly compared in genetically
      engineered mice. Both MPO-deficient (MPO-/-) and NADPH-oxidase-deficient (X
      linked chronic granulomatous disease [X-CGD]) mice showed increased
      susceptibility to pulmonary infections with Candida albicans and Aspergillus
      fumigatus compared with normal mice, and the X-CGD mice exhibited shorter
      survivals than MPO-/- mice. This increased mortality of X-CGD mice was associated
      with a 10- to 100-fold increased outgrowth of the fungi in their organs during
      the first 6 days. These results suggest that superoxide (O2-) produced by NADPH
      oxidase is more important than hypochlorous acid (HOCl) produced by MPO, although
      both oxidative products obviously contribute to the host defense against
      pulmonary infection with those fungi. We also observed that MPO-/-/X-CGD double
      knockout mice showed comparable levels of susceptibility to the X-CGD mice
      against C. albicans and A. funigatus, indicating that MPO is unable to play a
      role in host defense in the absence of NADPH-oxidase. This strongly suggests that
      hydrogen peroxide, the precursor of HOCl, is solely derived from O2- produced by
      NADPH-oxidase.

PMID- 12521120
TI  - Epidemiological aspects of clinical and environmental Cryptococcus neoformans
      isolates in the Brazilian state Rio Grande do Sul.
AB  - Cryptococcus neoformans is a pathogenic fungus that causes life-threatening
      meningoencephalitis in immunocompromised patients (HIV-positive patients), and
      lymphoproliferative disorders in patients subjected to organ transplantation and
      other immunosuppressive therapies. This fungus is commonly found in soil and
      avian excreta, mainly from pigeon and turkey. We describe the isolation and
      characterization of 17 clinical and 10 environmental (pigeon excreta) isolates
      from the Brazilian state Rio Grande do Sul. We analyzed capsule formation, carbon
      assimilation pattern, canavanine-glycine-bromothymol blue (CGB) reaction, and
      nitrate and urease tests, as well as susceptibility to antifungal drugs. The
      genetic variability among C. neoformans isolates was studied using randomly
      amplified polymorphic DNA (RAPD) analysis. Eight of 22 arbitrary polymerase chain
      reaction primers used confirmed genetic polymorphism among the environmental
      isolates tested, suggesting that it remains feasible to use RAPD analysis as a
      typing method. Three of the selected primers yielded 10 molecular subclasses. The
      majority of the clinical isolates were assigned to the molecular subclass F. The
      RAPD data obtained reinforce the developing consensus about the population
      structure of this fungus.

PMID- 12521121
TI  - Arachnomyces kanei (anamorph Onychocola kanei) sp. nov., from human nails.
AB  - Five isolates of a slow-growing cycloheximide resistant hyphomycetous fungus were
      obtained from nail specimens and investigated for their relationship to
      Onychocola canadensis (teleomorph Arachnomyces nodosetosus), a known agent of
      onychomycosis. In one patient diagnosed with superficial white onychomycosis,
      etiology was confirmed by a nail sample showing atypical filaments in direct
      microscopy, and by a follow-up specimen yielding cultures of the same fungus. A
      case of mixed infection with Aspergillus sydowii was also confirmed after
      examination of cultures grown from three successive microscopic-positive hallux
      nail specimens. For other isolates, etiological significance could not be
      confirmed by repeat sampling or results of direct microscopy were negative or
      unknown. Mating experiments yielded setose ascomata containing smooth oblate
      ascospores typical of Arachnomyces species. Phylogenetic analysis of ITS 2 region
      sequences support the conspecificity of the isolates and their placement within
      the genus. A. kanei sp. nov. (anamorph O. kanei sp. nov.) is described.

PMID- 12521122
TI  - Role of mitochondrial carrier protein Mrs3/4 in iron acquisition and oxidative
      stress resistance of Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a pathogenic basidiomycete that causes meningitis in
      immunocompromised patients. In this paper, we demonstrate that a previously
      described oxidant-sensitive mutant, oxy1, has constitutive ferric reductase and
      iron uptake, similar to a ferric reductase regulatory mutant, frr1. Through
      meiotic genetic analysis, we show that the two mutations are allelic. By
      complementation of frr1 with a genomic library, we isolated a gene, MRS3/4. The
      encoded protein is a putative solute transporter of the inner mitochondrial
      membrane. Disruption of this gene led to high ferric reductase, iron uptake and
      iron content, as well as increased sensitivity to hydrogen peroxide and slow
      growth in low iron medium. The disrupted gene is allelic with oxy1 and frr1. We
      sequenced the oxy1 and frr1 alleles of MRS3/4 and found that the frr1 mutation
      results in a premature stop codon, while the oxy1 mutation results in the
      substitution of a highly conserved glutamate residue with lysine. The Mrs3/4
      protein appears to be involved in mitochondrial iron transport in eukaryotes.
      Resistance to strong oxidants requires stringent control of iron metabolism.

PMID- 12521123
TI  - A note on the isolation of Cryptococcus neoformans serotype A MATa strain from
      the Italian environment.
AB  - The first known mating-competent isolate of Cryptococcus neoformans serotype A
      MATa (CBS 9172/ATCC MYA 2742), recently reported, was found during an
      environmental study of a rural aviary in the Italian province of Apulia. Data are
      presented to facilitate the finding of more such isolates.

PMID- 12521124
TI  - Expression of SSX-2 and SSX-4 genes in neuroblastoma.
AB  - The SSX genes are members of the family of cancer/testis antigens that encode
      tumor-associated antigens recognizable by autologous cytolytic T lymphocytes.
      Their expression is common in tumors of diverse lineages and absent in normal
      tissues except testis and thyroid. In this study, sixty-seven neuroblastomas (NB)
      (12 stage 1, 13 stage 2, 12 stage 3, 12 stage 4S and 13 stage 4) were examined by
      RT-PCR and a sensitive chemiluminescent detection method for SSX-2 and SSX-4
      expression. Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67%
      (12/18) expressed SSX-4. SSX-2 and SSX-4 positivity correlated with metastatic NB
      stage 4 (p=0.02 and p=0.006, respectively). Sensitivity experiments showed SSX-2
      detection was one tumor cell in 10(6) normal cells, and one in 10(4) for SSX-4.
      All normal tissues (n=6), with the exception of testis, normal bone marrow (BM,
      n=12) and normal peripheral blood (PBL, n=10) were negative for SSX-2 and SSX-4
      expression. Thirty-two BM and 14 PBL obtained from 35 stage 4 NB patients at 24
      months from their diagnosis were evaluated for SSX-2 expression. Unlike another
      cancer/testis antigen, GAGE, only one BM sample was positive, and no prognostic
      utility could be established. Further investigation of SSX expression at other
      relevant time points is warranted.

PMID- 12521125
TI  - Genomic instability on hMSH2, hMLH1, CD48 and IRF4 loci in pulmonary sarcoidosis.
AB  - Pulmonary sarcoidosis shares certain features with immune disease and neoplasia,
      and microsatellite DNA alterations are detectable in sputum specimens of
      pulmonary sarcoidosis patients. The biological basis and significance of these
      findings remain obscure, while information regarding the genetic basis of the
      disease is limited. Using multiplex PCR-based microsatellite analysis, we
      investigated 40 markers located on 1p, 1q, 2p, 2q, 3p, 5q, 6p, 7p, 9p, 11q, 14q
      and 17p in 38 sputum specimens of pulmonary sarcoidosis patients. Loss of
      heterozygosity (LOH) was found in 13 of 38 (34.2%) patients in at least one
      locus. These alterations occurred in the subset of markers located in or close to
      DNA mismatch repair (MMR) genes, hMSH2 (2p22.3-p16.1) and hMLH1 (3p2l.32-p21.1),
      as well as in CD48 (1q21-q23) and IRF4 (6p23-p25), genes associated with
      lymphocyte activation. Microsatellite instability (MIN) was observed in five
      cases (13.2%) in at least one locus. Our data suggest that genomic instability in
      pulmonary sarcoidosis could be due to MMR defects, while alterations of
      lymphocyte-specific agents could account for granuloma formation.

PMID- 12521126
TI  - Prognostic value of CA 15.3 kinetics for metastatic breast cancer.
AB  - Up to 80% of breast cancer patients developing metastases have high levels of CA
      15.3. We studied the prognostic implications of CA 15.3 kinetics in 119 patients
      before and at first metastasis by univariate and multivariate statistics. At
      first metastasis, CA 15.3 was elevated in 82.4% of patients, with a lead time
      (median 162 days) in 42.0% of them. Kaplan-Meier analysis showed overall survival
      (median 1477 days) to be significantly related to estrogen receptor (ER) and
      progesterone receptor (PgR) status (p=0.0001) and tumor size (p=0.025). The
      interval between diagnosis and first abnormal CA 15.3 (p=0.0001), the CA 15.3
      concentration (p=0.013), and the presence or absence of a lead time (p=0.001)
      also had prognostic value. ER and PgR status (p=0.0005 and p=0.0103,
      respectively), metastasis-free interval (p=0.0003), existence of a CA 15.3 lead
      time (p=0.0028), and days from diagnosis to first abnormal CA 15.3 (p=0.0055)
      entered in the Cox model. After first metastasis (median survival 573 days), ER
      and PgR status (p=0.0001 and p=0.0004, respectively), existence of a lead time
      for CA 15.3 (p=0.0138), and the concentration of first abnormal CA 15.3
      (p=0.0145) had individual prognostic value. In the Cox model ER status
      (p=0.0001), nodal status (p=0.0191), existence of a lead time for CA 15.3
      (p=0.0033), days from diagnosis to first abnormal CA 15.3 (p=0.0132), and
      concentration of first abnormal CA 15.3 (p=0.0320) were found to be independent
      prognostic variables. Compared to a matched historical control group that was not
      monitored by CA 15.3 assaying (n=140), the study group had a significantly longer
      survival after the first metastasis (p=0.0005). In conclusion, the kinetics of CA
      15.3 before the first metastasis is of prognostic value. When associated with 18
      fluorodeoxyglucose imaging, serial CA 15.3 assays may help to implement early
      treatment of metastases.

PMID- 12521127
TI  - Value of percent free prostate-specific antigen for the prediction of
      pathological stage in men with clinically localized prostate cancer.
AB  - PURPOSE: To analyze if the percentage of free prostate-specific antigen (PSA) can
      provide additional information to the combination of local clinical stage, serum
      PSA and Gleason score in the prediction of final stage and pathological features
      of prostate cancer. MATERIALS AND METHODS: A group of 480 men with clinically
      localized prostate cancer underwent lymphadenectomy and radical prostatectomy.
      Total and free PSA were measured in preoperative serum. Clinical stage was T1 in
      70.4% of patients and T2 in 29.6%. The biopsy Gleason score ranged between 2 and
      4 in 5.6%, between 5 and 7 in 78.4%, and was higher than 7 in 16%. Total serum
      PSA was below 4.1 ng/mL in 4.3%, between 4.1 and 10 ng/mL in 66.4%, between 10.1
      and 20 ng/mL in 22.5%, and higher than 20 in 6.7% of patients. The tumor was
      organ-confined in 49.8% and specimen-confined in 64.2%, and its pathological
      features were favorable in 35%. RESULTS: Multiple logistic regression analysis
      demonstrated that percent free PSA has independent predictive value for
      pathological stage only in the subset of patients with cT1 tumors and serum PSA
      between 4.1 and 10 ng/mL. In this group the probability of organ-confined cancer
      was 68.3% if the percent free PSA was above 15 and 56.3% if it was lower
      (p<0.001). The probability of specimen-confined disease was 86.6% and 71.3%,
      respectively (p<0.007), and the probability of favorable pathology was 59.8% and
      39.6%, respectively (p<0.002). We also found higher rates of organ- and specimen
      confined tumors and favorable pathology for every Gleason score when the percent
      free PSA was higher than 15. CONCLUSIONS: Percent free PSA seems to provide
      additional information to the combination of clinical stage and Gleason score for
      the prediction of pathological features only in patients with clinical stage T1c
      and serum PSA between 4.1 and 10 ng/mL.

PMID- 12521128
TI  - Metabolic effects of single-dose pamidronate administration in prostate cancer
      patients with bone metastases.
AB  - BACKGROUND: Increased osteolysis usually accompanies sclerotic bone metastases
      from prostate cancer. This provides a rationale for the use of bisphosphonates to
      treat bone pain and prevent skeletal complications. METHODS: The fasting urinary
      levels of calcium, hydroxyproline (OHPRO), pyridinolines (PYD),
      deoxypyridinolines (DPYD), collagen cross-linked N-telopeptide (NTX) and the
      serum values of calcium, total alkaline phosphatase and relevant bone isoenzyme,
      bone gla protein (BGP), carboxy-telopeptide of type I collagen (ICTP) and
      parathyroid hormone (PTH) were determined at baseline and on the 15th, 30th, 60th
      and 90th days after single-dose (90 mg) pamidronate administration in 35
      consecutive prostate cancer patients with bone metastases. These biochemical
      indices and serum interleukin 6 (IL-6) were also measured after four days in the
      last consecutive 17 cases. RESULTS: PYD, DPYD and NTX showed a significant
      decrease lasting four weeks (p<0.01, <0.01 and <0.001, respectively). OHPRO and
      ICTP did not change significantly. The NTX decline was greater than that of PYD
      and DPYD (maximum percent decrease: -71.3, -23.1 and -28.2, respectively). Bone
      formation markers and serum calcium did not change significantly. Serum PTH
      showed a rapid initial increase followed by a slow decrease (p<0.001). DPYD and
      NTX patterns did not correlate with changes in bone pain. As observed in the last
      17 cases, the maximum osteolysis inhibition after pamidronate occurred on the
      fourth day after drug infusion. Serum IL-6 levels showed a short-lived decrease
      preceded by a transient rise on the fourth day. CONCLUSIONS: Pamidronate is able
      to induce a decrease in bone resorption without significantly influencing bone
      formation. The maximum decrease in bone resorption occurs very early. NTX is the
      most sensitive bone resorption marker in bisphosphonate therapy monitoring.
      Changes in IL-6 but not bone resorption markers may be useful in the prediction
      of symptomatic response.

PMID- 12521129
TI  - Serum levels of tartrate-resistant acid phosphatase-5b in breast cancer patients
      treated with pamidronate.
AB  - A novel immunoassay specific for the osteoclast-produced TRAP isoform 5b has been
      developed recently. By means of this assay we studied the usefulness of serum
      TRAP-5b in monitoring the response to palliative treatment with pamidronate in
      breast cancer patients with bone metastases. We correlated serum TRAP-5b levels
      with pain intensity and intake of analgesics to assess the possible utility of
      the marker in identifying patients who could benefit from pamidronate treatment.
      Twenty-eight advanced breast cancer patients with bone metastases entered the
      study. Patients were treated according to the following schedule: two two-week
      cycles of 60 mg/week pamidronate IV, with a three-week interval in between (six
      infusions over seven weeks), followed by one infusion every three weeks for a
      total of 24 infusions over a treatment period of 61 weeks. Blood samples were
      taken before the start of treatment and before each infusion during two treatment
      cycles. To measure serum TRAP levels we employed the new immunoassay kit BoneTRAP
      produced by Suomen Bioanalytiikka Oy (SBA), Oulu, Finland. In order to assess the
      usefulness of this marker in evaluating the response to pamidronate treatment we
      divided patients into two groups (group A, worsened; group B, improved) with
      respect to pain trend and analgesic intake. Our results did not show any
      statistically significant difference in baseline serum TRAP levels in the two
      groups. However, one week after the first pamidronate infusion TRAP-5b serum
      levels decreased by 39% and 18% in groups A and B, respectively (p=0.01); these
      levels persisted throughout the treatment period. In conclusion, a decrease in
      TRAP-5b serum levels may reflect the pharmacological activity of pamidronate and
      seems to predict pain relief and a reduction in analgesic consumption.

PMID- 12521130
TI  - Comparison of single and dual platform methodologies for the estimation of CD34+
      hematopoietic progenitor cells: correlation with colony assay.
AB  - In this study three assays for the enumeration of CD34+ progenitors were
      compared: 1) a modified version of the Milan protocol, used in the standard dual
      platform format; 2) a dual-platform version of the ISHAGE protocol; 3) the
      ProCOUNT software version 2.0/ProCOUNT kit. The assays were compared to validate
      the accuracy of CD34+ cell counts in mobilized peripheral blood (PB), apheresis
      products (AP), and cord blood (CB). The ProCOUNT protocol uses reference beads
      for absolute CD34+ cell counting, whereas CD34 counts by other techniques are
      derived from a separate leukocyte count performed by a hematology analyzer. A
      good correlation between the ISHAGE and ProCOUNT methods was obtained for
      estimation of CD34+ counts in PB (n=42 samples analyzed) and AP (n=35)--except
      for samples having a leukocyte count >25 x 10(9)/L or a CD34 count <0.0025 x
      10(9)/L)--while a suboptimal correlation between the methods was observed for CB
      (n=30). The ProCOUNT system proved to be effective in reducing the variability in
      CD34+ cell counting and appeared to be useful for intralaboratory methodology
      standardization. The main disadvantage of the ProCOUNT assay was its inability to
      calculate CD34 counts in leukopenic samples and in CB samples showing a high
      erythroblast count. As far as the correlation with hematopoietic colonies is
      concerned, data collected from apheresis samples showed a good correlation
      between the three flow cytometry methods and colony-forming unit granulocyte
      macrophage (CFU-GM) counts, confirming the value of the flow cytometric test as a
      real-time, truly predictive test to measure the hematopoietic potential of the
      graft. In summary, all methods are suitable for enumeration of most PB samples,
      while the single-platform methodology should be preferred for the analysis of AP
      and CB. We also found the dual-platform format of the ISHAGE method precise and
      accurate for the estimation of CD34+ cells from CB samples. Based on these data
      it can be concluded that the single-platform flow cytometry assay format should
      be the preferred approach for CD34+ stem cell enumeration in different types of
      samples.

PMID- 12521131
TI  - The role of big endothelin-1 in colorectal cancer.
AB  - INTRODUCTION: Changes in liver blood flow caused by an unknown splanchnic
      vasoconstrictor have been noted in colorectal cancer patients with liver
      metastases. This prospective study was performed to assess whether plasma levels
      of big endothelin-1 (big ET-1) were raised in patients with colorectal cancer.
      METHODS: Plasma samples from peripheral vein of patients who underwent surgery
      for primary colorectal cancer (n=60) and those with known colorectal liver
      metastases (n=45) for a period of 15 months were taken prior to treatment and
      compared to age- and sex-matched controls (n=20). Plasma samples were analysed by
      using a single-step sandwich enzyme immunoassay. Immunohistochemistry and in situ
      hybridisation were also performed on tumour sections to investigate the
      expression of ET-1 by cancer cells. RESULTS: The median (range) plasma
      concentration of big ET-1 in controls was 2.1 pg/mL (1.2-13.4 pg/mL). The median
      (range) plasma concentration of big ET-1 in colorectal cancer patients with no
      overt hepatic metastases was 3.8 pg/mL (1.2-15.8 pg/mL), p=0.002, and the median
      (range) plasma concentration of big ET-1 in colorectal cancer patients with
      hepatic metastases was 5.2 pg/mL (1.7-30 pg/mL), p=0.0001; both were
      significantly elevated compared to the control group. A significant difference in
      immunostaining for big ET-1 was noted between paired normal colonic mucosa
      (median score-1) and tumour sections (median score-3), p=0.01. CONCLUSION: This
      study has demonstrated elevated concentrations of big ET-1 in colorectal cancer
      patients, especially in those with hepatic metastases. Upregulation of ET
      activity in colorectal cancer could be inferred by the increased immunostaining
      of big ET-1 in cancer cells. Therefore, plasma big ET-1 levels should be
      evaluated as a potential tumour marker for the identification of hepatic
      metastases at an earlier stage.

PMID- 12521132
TI  - Diagnostic value of plasma vascular endothelial growth factor as a tumor marker
      in patients with non-small cell lung cancer.
AB  - We assessed the diagnostic value of circulating VEGF as a tumor marker in
      patients with lung cancer and compared its clinical utility with that of other
      markers such as carcinoembryonic antigen (CEA) and cytokeratin 19 (CYFRA). One
      hundred and sixty non-small cell lung cancer patients and 70 healthy volunteers
      were included in the study. Circulating VEGF was assessed by enzyme-linked
      immunosorbent assay (ELISA). The serum concentrations of both CEA and CYFRA were
      measured by means of immunoradiometric assays. The diagnostic value of plasma
      VEGF (VEGFp) was better than that of CYFRA and similar to that of CEA. When the
      diagnostic value of VEGFp and CEA for the diagnosis of adenocarcinoma was
      compared, the two markers proved to have nearly equal discriminatory power. In
      diagnosing squamous cell carcinoma, VEGFp showed less discrimination than CYFRA.
      When the diagnostic value of VEGFp was analyzed for stage I adenocarcinoma
      patients, VEGFp was slightly more discriminatory than CEA. The combination assay
      of VEGFp and CEA had a sensitivity of 75% and a specificity of 60% at a cutoff of
      104.4 pg/mL for VEGFp and 5.2 ng/mL for CEA. The combination of VEGF and CEA was
      superior to CEA alone in the early diagnosis of adenocarcinoma of the lung.

PMID- 12521133
TI  - Interaction of CD44 with different forms of hyaluronic acid. Its role in adhesion
      and migration of tumor cells.
AB  - Interaction between hyaluronic acid (HA) and CD44 has been considered a key event
      in tumor invasion and metastasis. HA is a linear, high molecular weight
      glycosaminoglycan in its native state, but fragmented low molecular forms are
      found at sites ofneoplastic or inflammatory infiltrates. Both high and low
      molecular weights HA are involved in diverse biological functions. In this study,
      we used two clonal variants of a T cell murine lymphoma designated LBLa and LBLc.
      These cell lines were found to differ in their in vivo and in vitro growth rates.
      LBLa grew faster and exhibited an enhanced invasive capacity as compared to LBLc.
      In contrast, cell lines did not differ in the expression of surface markers (CD8,
      CD24, CD25, CD44, and CD18), or in their capacity to bind HA. However, LBLa cells
      exhibited higher capacity to migrate to low molecular weight HA than did LBLc.
      Migration was mediated by CD44 since it was abrogated by anti-CD44 monoclonal
      antibody as well as by hyaluronidase. We suggest that interaction between CD44
      and low molecular weight HA may trigger migration mechanisms in LBLa cells, thus
      contributing to enhanced invasive cell capacity.

PMID- 12521134
TI  - Expression level of neural cell adhesion molecule (NCAM) inversely correlates
      with the ability of neuroblastoma cells to adhere to endothelium in vitro.
AB  - The precise function of cell adhesion molecules in the hematogenous phase of
      neuroblastoma metastasis is poorly understood. The aim of this study was to
      investigate whether neural cell adhesion molecule (NCAM) modulates neuroblastoma
      cell (NB) adhesion and transendothelial penetration in a coculture model. Our
      data, assessed on 11 NB cell lines, demonstrate an inverse correlation between
      NCAM expression and NB cell adhesion. Transfection of the NB cell line UKF-NB-4
      with a cDNA encoding the human NCAM-140 kD isoform enhanced NCAM expression and
      the amount of tumor cell aggregates, reduced the amount of single tumor cells,
      and diminished initial NB cell adhesion to an endothelial cell monolayer.
      Treatment of UKF-NB-4 with NCAM antisense oligonucleotides reduced NCAM surface
      level, increased the number of single tumor cells, and induced up-regulation of
      NB cell adhesion to endothelium. Modulation of NCAM expression had no effect on
      transendothelial penetration. Fluorescence analysis revealed a down-regulation of
      NCAM in single tumor cells, prior to NB adhesion. The data support the view that
      low levels of NCAM are necessary for NB cells to leave a tumor cell aggregate and
      adhere to endothelial cells.

PMID- 12521135
TI  - The microenvironment of AFT024 cells maintains primitive human hematopoiesis by
      counteracting contact mediated inhibition of proliferation.
AB  - We have previously shown that maintenance of primitive human hematopoietic stem
      cells is poor when cultured in contact with marrow stromal feeders. However, when
      separated from stromal contact, human progenitors can be maintained because
      adhesion mediated proliferation inhibition does not occur. In this study we
      demonstrate how the murine fetal liver cell line, AFT024, supports primitive
      human hematopoiesis better in contact cultures compared to primary feeders. We
      evaluated if better progenitor maintenance in contact with AFT024 cells can be
      explained by decreased adhesion itself or decreased adhesion mediated inhibition
      of proliferation. We show that primitive human hematopoietic cells adhered
      equally well to AFT024 and primary feeders, such as M2-10B4. Further, contact
      with metabolically inactive AFT024 cells prevented cell cycle progression and
      decreased maintenance of primitive progenitors to the same extent as contact with
      M2-10B4 feeders. However, contact with viable AFT024 feeders did not inhibit
      proliferation, suggesting that AFT024-factors counteract contact mediated
      inhibition of proliferation. Cytokine production by M2-10B4 and AFT024 cells was
      similar. Large-size O-sulfated heparan sulfate glycosaminoglycans, known to be
      important for hematopoietic support, were found only in AFT024-matrix. We
      hypothesize that these factors may explain, in part, our observations. Finally,
      we show that more than 100% of primitive myeloid progenitors could be maintained
      for at least five weeks when cultured in contact with AFT024 feeders in the
      presence of Interleukin-3 and Macrophage Inflammatory Protein-1alpha. In
      conclusion, AFT024 cells produce factor(s), that counteract contact induced
      growth inhibition of primitive human hematopoietic progenitors, leading to
      expansion of these cells in contact with the microenvironment.

PMID- 12521136
TI  - Local cell membrane deformations due to receptor-ligand bonding as seen by
      reflection microscopy.
AB  - Understanding surface receptor clustering and redistribution processes at the
      cell-matrix contact zone requires detailed knowledge of the spatial integration
      of these molecules in the architecture of this complex interface. Here we present
      and discuss critically a procedure to extract such information combining
      reflection contrast microscopy (RCM) and reflection interference microscopy
      (RIM). As model system, we used living human umbilical vein endothelial cells
      (HUVEC) adhering to laminin-coated surfaces and investigated the distribution of
      the alpha2beta1 (CD29/CD49b) integrin at the contact zone of these cells. First,
      we applied freeze-fracture electron microscopy to gain information on microscopic
      details of the alpha2beta1 distribution at the contact zone. Next, we visualized
      and analyzed the overall lateral distribution of the integrins applying RCM using
      immunogold-labeling with 10 nm labels and a special silver enhancement technique.
      We found that RCM can be used to determine the lateral position of the marked
      receptor molecules to an accuracy of about 100-200 nm, instead of large
      morphological changes at the contact zone during silver enhancement. Finally, we
      combined RCM with RIM and analyzed the interference pattern of the contact zone
      around the label positions. Thus, we were able to detect changes of the average
      shape of the cell membrane due to receptor-ligand bonding of a size down to the
      resolution of the techniques.

PMID- 12521137
TI  - The effects of elutriates from PAH and heavy metal polluted sediments on
      Crassostrea gigas (Thunberg) embryogenesis, larval growth and bio-accumulation by
      the larvae of pollutants from sedimentary origin.
AB  - The release, bio-availability and toxicity of contaminants, when sediments are
      resuspended have been examined, studying concurrently their effects on the
      embryogenesis and on the larval growth of the Crassostrea gigas larvae and their
      bio-accumulation in those organisms. Three characteristic sediments have been
      selected (one contaminated by PAHs, a second by heavy metals and the last by the
      both pollutants). The organisms were directly exposed to elutriates obtained from
      each sediment or fed on algae (Isochrysis galbana) contaminated with the same
      elutriates. The elutriates used in this study show contamination levels similar
      to those observed in some polluted coastal and estuary environments. The larval
      growth test has appeared to be more sensitive that the embryotoxicity test. The
      biological effects and the contaminant bio-accumulation were more pronounced when
      larvae were directly exposed to different elutriates. In the case of PAHs, the
      contamination of algae was sufficient to lead to effect on the larval growth of
      the Crassostrea gigas. In all cases, a fraction of contaminants adsorbed on
      suspended particles was bio-available and accumulated by the larvae. This study
      has shown that resuspending polluted sediments constitutes a threat to pelagic
      organisms and than the C. gigas larval growth may be proposed as a test to
      protect the most sensitive areas.

PMID- 12521138
TI  - Lead burdens and behavioral impairments of the lined shore crab Pachygrapsus
      crassipes.
AB  - Sublethal burdens of lead impair behaviors critical to survival in a variety of
      animals. In a test arena, I measured refuge-seeking behaviors of adult, male,
      lined shore crabs from lead-free and lead-contaminated sites. The body sizes of
      the test groups did not differ although the mean total body lead burdens differed
      by over 2,300%. A lead-contaminated environment does not appear to affect growth.
      Each of the 31 crabs had at least six trials in the arena. The fraction of trials
      with more than one pause, number of pauses per trial, mean time per pause, and
      the fraction of time a crab spent in pauses did not differ between groups. The
      absence of behavioral effects of the lead burdens may be because a large portion
      of the lead burden was sequestered in the carapace. The neurological and other
      soft tissues would then have lower levels of lead. Predators that ingest
      primarily soft tissues would have little exposure to the lead burden of these
      crabs. Those that also ingest the carapace may benefit from its high calcium
      content that inhibits lead uptake from the gut, regardless of the location of
      lead in the crab body.

PMID- 12521139
TI  - Window of sensitivity for the estrogenic effects of ethinylestradiol in early
      life-stages of fathead minnow, Pimephales promelas.
AB  - Sexual differentiation in fish occurs after hatching during early life-stages and
      is believed to be a time when the gonad has a heightened sensitivity to
      disruption by chemicals that mimic hormones. In this study fathead minnows
      (Pimephales promelas) were exposed to an environmentally relevant concentration
      of ethinylestradiol (EE2) for short intervals in fish early life-stages and
      vitellogenic and gonadal responses were measured at 30 and 100 dph (sexual
      maturity), respectively. All EE2 exposure regimes induced vitellogenin (VTG)
      synthesis and disruption in duct development (a feminization) in males, with a
      window of enhanced sensitivity between 10 and 15 dph (where 60% of the males had
      feminized ducts). There was an altered pattern in sex cell development in males
      (inhibition of spermatogenesis) in the solvent controls (ethanol 0.1 ml/l) and
      all EE2 treatments when compared with the dilution water controls. Furthermore,
      fewer spermatozoa were observed in the testis of males exposed to EE2 from 15 to
      20 dph and fertilized eggs (<24 h post-fertilization)-20 dph, compared with both
      the solvent and dilution water controls. These data show that short exposures of
      embryos/very early life-stage fathead minnows to an environmentally relevant
      concentration of EE2 lead to alterations in gonadal development that potentially
      have reproductive consequences and thus population level effects.

PMID- 12521140
TI  - Statistical analysis of sediment toxicity by additive monotone regression
      splines.
AB  - Modeling nonlinearity and thresholds in dose-effect relations is a major
      challenge, particularly in noisy data sets. Here we show the utility of nonlinear
      regression with additive monotone regression splines. These splines lead almost
      automatically to the estimation of thresholds. We applied this novel method to
      explore the relation between the toxicity of aquatic sediments, as observed in
      bioassays with Daphnia magna, Chironomus riparius and Vibrio fischeri, and the
      degree of contamination of the sediments. Despite the low signal-to-noise ratio
      in the data, some interesting thresholds and (non)linear effects were found. The
      method has added value compared to the linear multivariate methods applied
      earlier to these data. Percentages of explained variance remained low, but could
      be doubled by diminishing the effect of local variability.

PMID- 12521141
TI  - Biomarkers as diagnostic tools for evaluating effects of unknown past water
      quality conditions on stream organisms.
AB  - The following biomarkers were investigated in stream populations of juvenile
      brown trout (Salmo trutta f. fario) and gammarids (Gammarus pulex) to determine
      if crayfish mortality could have been confounded by pollutants: (1) alterations
      of fish liver ultrastructure, (2) fish gill and kidney histopathology, (3) stress
      protein (hsp70) expression in fish liver and gills and in gammarids, and (4)
      changes in various blood parameters of brown trout. In addition, the following
      measurements were conducted in parallel with the biological sampling: (a)
      chemical analyses including several pesticides, organochlorines, PCBs, and PAHs
      in sediment and tissue samples of brown trout and crayfish (Astacus astacus), and
      (b) limnochemical analyses of nutrients, electrolytes, dissolved oxygen content,
      temperature and pH. Biomarkers together with chemical and limnochemical analyses
      concomitantly indicated moderate pollution of the stream at all sampling sites.
      Biological data indicated a transient, episodic event at one sampling site
      resulting (a) in altered stress protein levels in gills and livers of trout and
      in whole gammarids as well as (b) in elevated numbers of macrophages in liver
      tissue. Biomarker responses provided spatial and temporal evidence that a
      contaminant release was associated with the crayfish mortalities observed in this
      stream system.

PMID- 12521143
TI  - Assimilation efficiency and toxicokinetics of 14C-lindane in the terrestrial
      isopod Porcellionides pruinosus: the role of isopods in degradation of persistent
      soil pollutants.
AB  - An achievable way to evaluate the bioavailability of a certain toxic in the
      environment is to measure the concentration inside soil organisms. Non-target
      saprotrophic organisms like isopods are often exposed to agrochemicals or other
      kind of persistent chemicals. In this study the isopod Porcellionides pruinosus
      was exposed to a constant concentration of Lindane (gamma-HCH) via food. Using
      toxicokinetic models the bioaccumulation and fate of the pesticide by isopods was
      assessed and compared with previous studies, where an unexpected decrease in
      gamma-HCH concentration was observed. Animal body burdens showed higher values,
      and a lower assimilation rate constant, although the elimination rate constant
      was twice the value previously observed. It was also observed that a significant
      amount of gamma-HCH had an unknown fate. To discover its possible destiny, a
      factorial experiment was carried out using two types of CO2 traps and
      contaminated leaves in the presence and absence of isopods. It was concluded that
      isopod activity might have been responsible for a more rapid biotransformation of
      gamma-HCH in leaves, since the amount of the pesticide is reduced in their
      presence.

PMID- 12521142
TI  - Histopathologic biomarkers in three spined sticklebacks, Gasterosteus aculeatus,
      from several rivers in Southern England that meet the freshwater fisheries
      directive.
AB  - This study demonstrates the utility and sensitivity of histopathologic biomarkers
      by recording lesions to the gill, liver and spleen in three spined sticklebacks
      (Gasterosteus aculeatus) from several rivers in Southern England which broadly
      comply with the water quality directives to protect fish health. The main study
      site was the Letcombe Brook system near Wantage, graded 1 (good) to 3 (fair) by
      the Environment Agency, using the River Ecosystem (RE) Class system. Sites with
      similar grades on the rivers Erme, Clyst, Exe and Plym were also selected in
      Devon. A normal condition factor (0.9 +/- 0.02, mean +/- S.E., n = 90), the
      presence of food in the stomach, and the whole body ionic composition (Na, K, Mg,
      Ca, Cu, Zn) suggested that fish were generally healthy. All fish showed some
      minor incidence of gill and liver lesions, even in the best (grade RE1) river
      water quality. Scoring the percentage of branchial secondary lamellae showing
      lesions did not reflect water quality because of biotic factors such as parasite
      load. However, fatness of secondary lamellae (length/width) increased in lower
      class rivers. Hepatic fatty change and focal necrosis was related to river
      quality grades with fatty change increasing from 0.8% to 12% of total liver area
      in grade RE1 and RE2 rivers, respectively. The gross anatomy of the spleen showed
      normal red and white pulp, and sinusoid space varied between 11% and 34% of the
      tissue area, but was not correlated with river grade. Overall, we conclude that
      histopathologic lesions are present in fish even when water quality meets the
      Freshwater Fisheries Directive. The Directive therefore only partly protects fish
      health. The incidence of fatty change in the liver, or fatness of secondary
      lamellae, in adult three spined sticklebacks are suggested as simple but
      sensitive histopathologic biomarkers which may be used to protect freshwater
      fishes as a novel alternative approach to water quality based Directives. We
      propose histopathologic biomarkers of the three spined stickleback for routine
      monitoring of fish health in EU freshwaters.

PMID- 12521144
TI  - The usefulness of elemental iron for cereal flour fortification: a SUSTAIN Task
      Force report. Sharing United States Technology to Aid in the Improvement of
      Nutrition.
AB  - Fortification of cereal flours may be a useful public health strategy to combat
      iron deficiency. Cereal flours that are used shortly after production (e.g.,
      baking flour) can be fortified with soluble iron compounds, such as ferrous
      sulfate, whereas the majority of flours stored for longer periods is usually
      fortified with elemental iron powders to avoid unacceptable sensory changes.
      Elemental iron powders are less well absorbed than soluble iron compounds and
      they vary widely in their absorption depending on manufacturing method and
      physicochemical characteristics. Costs vary with powder type, but elemental iron
      powders are generally less expensive than ferrous sulfate. This review evaluates
      the usefulness of the different elemental iron powders based on results from in
      vitro studies, rat assays, human bioavailability studies, and efficacy studies
      monitoring iron status in human subjects. It concludes that, at the present time,
      only electrolytic iron powder can be recommended as an iron fortificant. Because
      it is only approximately half as well absorbed as ferrous sulfate, it should be
      added to provide double the amount of iron.

PMID- 12521145
TI  - Effect of n-3 polyunsaturated fatty acids on risk reduction of sudden death.
AB  - Two recent reports confirm the role of n-3 polyunsaturated fatty acid (PUFA)
      consumption in risk reduction for sudden death. The mechanism likely involves an
      antiarrhythmic effect, further supporting the role of dietary n-3 PUFA in
      maintenance of human health.

PMID- 12521146
TI  - Homocysteine, folate deficiency, and Parkinson's disease.
AB  - Folate deficiency sensitizes mice to dopaminergic neurodegeneration and motor
      dysfunction caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). Additional experiments indicate that this effect of folate deficiency may
      be mediated by homocysteine. These findings suggest that folate deficiency and
      hyperhomocysteinemia are risk factors for Parkinson's disease.

PMID- 12521147
TI  - Abdominal aortic aneurysm.

PMID- 12521148
TI  - Case of the month. Ischemic colitis.

PMID- 12521149
TI  - CT quantification of pulmonary emphysema: assessment of lung structure and
      function.
AB  - Accurate diagnosis and quantification of pulmonary emphysema in vivo is important
      to understand the natural history of the disease, to assess the extent of the
      disease, and to evaluate and follow-up therapeutic interventions. Because
      pulmonary emphysema is defined by pathology, new diagnostic methods for
      quantification should be validated by reference to pathological and histological
      standards. Recent studies have addressed the capability of computed tomography
      (CT) to accurately quantify pulmonary emphysema. These studies that have been
      overviewed in this article have been based on CT scans obtained after deep
      inspiration or expiration, on subjective visual grading, and on objective
      measurements of attenuation values by using dedicated software providing
      numerical data on two-dimensional and on three-dimensional approaches, and
      compared CT data with pulmonary function tests. More recently, fractal and
      textural analyses were applied to CT scans to assess the presence, extent, and
      types of emphysema. Quantitative CT has already been used in patient selection
      for surgical treatment of pulmonary emphysema and in pharmacotherapeutical
      trials. However, despite numerous and extensive studies already available, this
      technique has not yet been standardized, and important questions about how to
      best use CT for the quantification of pulmonary emphysema remain to be addressed.

PMID- 12521150
TI  - 3D-CT evaluation of metallic implants: principles, techniques, and applications.

PMID- 12521151
TI  - Microbial source tracking: state of the science.
AB  - Although water quality of the Nation's lakes, rivers and streams has been
      monitored for many decades and especially since the passage of the Clean Water
      Act in 1972, many still do not meet the Act's goal of "fishable and swimmable".
      While waterways can be impaired in numerous ways, the protection from pathogenic
      microbe contamination is most important for waters used for human recreation,
      drinking water and aquaculture. Typically, monitoring methods used for detecting
      potential pathogenic microorganisms in environmental waters are based upon
      cultivation and enumeration of fecal indicator bacteria (i.e. fecal coliforms, E.
      coli, and fecal enterococci). Currently, there is increasing interest in the
      potential for molecular fingerprinting methods to be used not only for detection
      but also for identification of fecal contamination sources. Molecular methods
      have been applied to study the microbial ecology of environmental systems for
      years and are now being applied to help improve our waters by identifying problem
      sources and determining the effect of implemented remedial solutions. Management
      and remediation of water pollution would be more cost-effective if the correct
      sources could be identified. This review provides an outline of the main methods
      that either have been used or have been suggested for use in microbial source
      tracking and some of the limitations associated with those methods.

PMID- 12521152
TI  - A taxing environment: evaluating the multiple objectives of environmental taxes.
AB  - Environmental taxes have attracted attention in recent years as a tool to
      internalize environmental externalities. This paper evaluates Sweden's experience
      with environmental taxes in the energy sector by examining how environmental
      taxes compare with estimated environmental externalities associated with the use
      of oil, coal, natural gas, and forest residue fuels. We also analyze how
      environmental taxes influence fuel choices in the energy sector by comparing the
      production, environmental, and tax costs for the same fuels. We find that (i) the
      Swedish environmental taxes correspond imperfectly with environmental costs; (ii)
      the Swedish tax and subsidy system introduces changes in fuel choice decisions;
      (iii) the energy users are responding to the incentives created by the tax and
      subsidy systems in ways that are consistent with economic theory; and (iv) the
      Swedish experience with environmental taxes and subsidies bears directly on wider
      evaluations of energy policy approaches internationally.

PMID- 12521153
TI  - Impacts of phosphate amendments on lead biogeochemistry at a contaminated site.
AB  - Soil amendments can be used to cost-effectively reduce the bioavailability and
      mobility of toxic metals in contaminated soils. In this study a field
      demonstration was conducted at a Pb-contaminated site to evaluate the
      effectiveness of P-induced Pb immobilization. Phosphate was applied at a 4.0
      molar ratio of P to Pb with three treatments: T1, 100% of P from H3PO4; T2, 50% P
      from H3PO4 + 50% P from Ca(H2PO4)2; and T3, 50% P from H3PO4 + 5% phosphate rock.
      Phosphate amendments effectively transformed soil Pb from the nonresidual (sum of
      exchangeable, carbonate, Fe/Mn, and organic) to the residual fraction, with
      residual Pb increase by 19-48% for T1, 22-50% for T2, and 11-55% for T3,
      respectively. Lead immobilization was attributed to the P-induced formation of
      chloropyromorphite [Pb10(PO4)6Cl2], which was identified in the surface soil,
      subsurface soil, and plant rhizosphere soil. Occurrence of chloropyromorphite was
      evident 220 days after P addition for T1 and T2 treatments and 330 days for T3.
      Visual MINTEQ model and activity-ratio diagram indicated that lead phosphate
      minerals controlled Pb2+ activities in the P-treated soils. Phosphate treatments
      significantly reduced Pb translocation from the roots to the shoots in the St.
      Augustine grass (Stenotaphrum secundatum), possibly via the formation of
      chloropyromorphite on the cell walls of roots. This field observation suggested
      that P amendments are efficient in reducing Pb mobility via in situ formation of
      insoluble chloropyromorphite minerals at a field setting. Lead immobilization
      shows a long-term stability. A mixture of H3PO4 and phosphate rock yields the
      best overall results for in situ Pb immobilization, with less soil pH change and
      less P leaching. Application of combined H3PO4 with phosphate rock may provide an
      effective alternative to the current phosphate remediation technologies for
      contaminated soils.

PMID- 12521154
TI  - Using sulfur as a tracer of outdoor fine particulate matter.
AB  - Six homes in the metropolitan Boston area were sampled between 6 and 12
      consecutive days for indoor and outdoor particle volume and mass concentrations,
      particle elemental concentrations, and air exchange rates (AERs). Indoor/outdoor
      (I/O) ratios of nighttime (i.e., particle nonindoor source periods) sulfur, PM2.5
      and the specific particle size intervals were used to provide estimates of the
      effective penetration efficiency. Mixed models and graphical displays were used
      to assess the ability of the I/O ratios for sulfur to estimate corresponding I/O
      ratios for PM2.5 and the various particle sizes. Results from this analysis
      showed that particulate sulfur compounds were primarily of outdoor origin and
      behaved in a manner that was representative of total PM2.5 in Boston, MA. These
      findings support the conclusion that sulfur can be used as a suitable tracer of
      outdoor PM2.5 for the homes sampled in this study. Sulfur was more representative
      of particles of similar size (0.06-0.5 microm), providing evidence that the size
      composition of total PM2.5 is an important characteristic affecting the
      robustness of sulfur-based estimation methods.

PMID- 12521155
TI  - Hypoxia in the Baltic Sea and basin-scale changes in phosphorus biogeochemistry.
AB  - Deep-water oxygen concentrations in the Baltic Sea are influenced by
      eutrophication, but also by saltwater inflows from the North Sea. In the last two
      decades, only two major inflows have been recorded and the lack of major inflows
      is believed to have resulted in a long-term stagnation of the deepest bottom
      water. Analyzing data from 1970 to 2000 at the basin scale, we show that the
      estimated volume of water with oxygen, <2 mL L(-1), was actually at a minimum at
      the end of the longest so-called stagnation period on record. We also show that
      annual changes in dissolved inorganic phosphate water pools were positively
      correlated to the area of bottom covered by hypoxic water, but not to changes in
      total phosphorus load, thus addressing the legacy of eutrophication on a
      basinwide scale. The variations in phosphorus pools that have occurred during the
      past decades do not reflect any human action to reduce inputs. The long residence
      time and internally controlled variation of the large P pool in the Baltic Sea
      has important implications for management of both N and P inputs into this
      eutrophicated enclosed basin.

PMID- 12521156
TI  - Chromium speciation in rainwater: temporal variability and atmospheric
      deposition.
AB  - The concentrations of the various chromium species were determined in 89
      rainwater samples collected in Wilmington, NC, from October 1, 1999, to December
      31, 2001. Volume-weighted annual average concentrations of Cr(total), particulate
      Cr, Cr(III)(aq), and Cr(VI)(aq) were 4.6, 2.2, 0.8, and 1.2 nM, respectively.
      There was distinct seasonal and diurnal variability in the concentrations of the
      various chromium species. Chromium emissions to the global atmosphere by both
      natural and anthropogenic sources are estimated to be 2.2 x 10(9) mol/yr. Using
      our rainwater concentration data along with other published rainwater Cr
      concentrations and an estimate for total global annual rain, the total global
      flux of chromium removed from the atmosphere via wet deposition is 2.1 x 10(9)
      mol/yr. This represents complete removal of Cr and indicates that essentially all
      chromium released into the global atmosphere is removed via rain. About half this
      chromium is dissolved with roughly equal concentrations of toxic Cr(VI) and
      relatively harmless Cr(III) species.

PMID- 12521157
TI  - Release and phase partitioning of metals from anoxic estuarine sediments during
      periods of simulated resuspension.
AB  - Periodically, marine sediments are subjected to physical processes which
      resuspend them into the water column, releasing previously sequestered metals.
      The role of resuspension energy and duration on release and subsequent
      redistribution of sediment bound metals was measured experimentally using a
      particle entrainment simulator. Two metal contaminated anoxic sediments with
      different physical and chemical characteristics were resuspended for 12 h at
      energies of 2 and 5 dynes cm(-2). Samples were taken at specified intervals, and
      the water column pH, Eh and dissolved oxygen levels were monitored continuously.
      Over time, metal concentrations increased in the particulate (nonfilterable > or
      = 1 microm) and filterable (< 1 microm) phases of the overlying water. In
      general, metal enrichment followed the Irving-Williams order of complex
      stability. Overall, the sediment's chemical and physical composition were major
      factors in determining the amount of metal released, more so than the level of
      resuspension energy applied. These results provide insight into how physical and
      chemical processes interact during sediment resuspension to release sediment
      bound metals and control their phase distribution in the water column.

PMID- 12521158
TI  - In situ mobilization of colloids and transport of cesium in Hanford sediments.
AB  - Radioactive waste, accumulated during Pu production, has leaked into the
      subsurface from underground storage tanks at the U.S. Department of Energy's
      Hanford site. The leaking solutions contained 137Cs and were of high ionic
      strength. Such a tank leak was simulated experimentally in steady-state flow
      experiments with packed Hanford sediments. The initial leak was simulated by a 1
      M NaNO3 solution, followed by a decrease of ionic strength to 1 mM NaNO3. Cesium
      breakthrough curves were determined in both 1 M and 1 mM NaNO3 background.
      Colloidal particles were mobilized during the change of ionic strength. Mobilized
      colloids consisted mainly of quartz, mica, illite, kaolinite, and chlorite.
      Electrophoretic mobilities of colloids in the eluent solution were 
      3(microm/s)(V/cm) and increased to less negative values during later stages of
      mobilization. Mobilized colloids carried a fraction of the cesium along. While
      transport of cesium in 1 M NaNO3 background was much faster than in 1 mM NaNO3,
      cesium attached to colloids moved almost unretarded through the sediments. Cesium
      attached to mobilized colloids was likely associated with high affinity sorption
      sites on micas and illites.

PMID- 12521159
TI  - Photocatalytic atrazine degradation by synthetic minerals, atmospheric aerosols,
      and soil particles.
AB  - In this work, the photocatalytic atrazine degradation by seven synthetic minerals
      and five environmental particle samples was examined to investigate a possible
      contribution of photocatalysis to the abiotic degradation of atrazine in the
      environment. Particle suspensions containing 500 ng/L atrazine were irradiated
      with a sun simulator, and the atrazine degradation was monitored by enzyme-linked
      immunosorbent assay (ELISA). Atrazine detection by ELISA proved to be an useful
      analytical tool because of low cross-reactivity of atrazine metabolites and high
      sensitivity with detection limits in the lower nanograms per liter range. The
      atrazine degradation followed first-order kinetics, and the obtained rate
      coefficients were compared with the rate of direct photolysis. Known
      photocatalysts, such as TiO2 and ZnO, showed the expected fast photocatalytic
      degradation (k = 27-327 x 10(-3) min(-1)) of atrazine. The degradation rates
      detected upon irradiation of titanium-, zinc-, or iron-containing minerals were
      orders of magnitudes lower (k = 0.15-0.70 x 10(-3) min(-1)) but still
      significantly faster than direct photolysis without particles (k = 0.10 x 10(-3)
      min(-1)). With environmental particle samples (soot, fly ash, sand, road dust,
      and volcanic ash), however, no significant photocatalytic activity was observed
      (k = 0.07-0.16 x 10(-3) min(-1)). The atrazine degradation rates were in the
      range of direct photolysis. Thus photocatalysis by aerosol or soil particles
      appears not to enhance abiotic atrazine degradation in the environment.

PMID- 12521160
TI  - Abiotic reductive dechlorination of chlorinated ethylenes by iron-bearing soil
      minerals. 2. Green rust.
AB  - Abiotic reductive dechlorination of chlorinated ethylenes by the sulfate form of
      green rust (GR(SO4)) was examined in batch reactors. Dechlorination kinetics were
      described by a modified Langmuir-Hinshelwood model. The rate constant for
      reductive dechlorination of chlorinated ethylenes at reactive GR(SO4) surfaces
      was in the range of 0.592 (+/-4.4%) to 1.59 (+/-6.3%) day(-1). The specific
      reductive capacity of GR(SO4) for target organics was in the range of 9.86 (+/
      10.1%) to 18.0 (+/-4.3%) microM/g and sorption coefficient was in the range of
      0.53 (+/-2.4%) to 1.22 (+/-4.3%) mM(-1). Surface area-normalized pseudo-first
      order initial rate constants for chlorinated ethylenes by GR(SO4) were 3.4 to 8.2
      times greater than those by pyrite. Chlorinated ethylenes were mainly transformed
      to acetylene, and no detectable amounts of chlorinated intermediates were
      observed. The rate constants for the reductive dechlorination of
      trichloroethylene (TCE) increased as pH increased (6.8 to 10.1) but were
      independent of solid concentration and initial TCE concentration. Magnetite
      and/or maghemite were produced by the oxidation of GR(SO4) by TCE. These findings
      are relevant to the understanding of the role of abiotic reductive dechlorination
      during natural attenuation in environments that contain GR(SO4).

PMID- 12521161
TI  - Photocatalytic reduction and recovery of copper by polyoxometalates.
AB  - A series of polyoxometalates PW12O40(3-), SiW12O40(4-), and P2Mo18O62(6-) have
      been used as photocatalysts for recovery of copper and production of fine metal
      particles. The process involves absorption of light by polyoxometalates,
      oxidation of an organic substrate, for instance, propan-2-ol as sacrificial
      reducing reagent, and reoxidation of the reduced polyoxometalates by Cu2+ ions,
      closing the photocatalytic cycle. Copper(II) ions are reduced to copper(I) and
      finally to zero-state particles in a 2-electron process, as also suggested by the
      half-order dependence. Increase of catalyst or propan-2-ol concentration, or
      both, accelerates the photodeposition of copper until a saturation value is
      reached. The method is operational at a wide range of copper concentrations
      varying from 3 to 1300 ppm, leading to very low final concentrations (<0.2 ppm).
      The presence of dioxygen suppresses the initiation of copper recovery, though the
      process is equally effective after dioxygen is consumed. The process is
      independent of pH within the range 0.3-5.0. Addition of ClO4-, NO3-, or CH3COO-
      has no effect on the removal of copper ions. Chloride ions retard the enhancement
      of copper precipitation through stabilization of copper(I). This homogeneous,
      polyoxometalate-based process exhibits some benefits in comparison with the
      semiconductor-based (heterogeneous) recovery of metals: The final zero-state
      metal particles are obtained in pure form. No separation from the catalyst is
      needed, and moreover, the process is catalytic as the photodeposited metal
      particulates do not hinder the photocatalytic action of polyoxometalate anions.

PMID- 12521162
TI  - Reduced Cd accumulation in Zea mays: a protective role for phytosiderophores?
AB  - Cadmium is a nonessential trace metal and a frequent soil contaminant. Because
      plants vary in their accumulation of Cd, an understanding of the specific
      processes that control uptake could reveal methods for reducing Cd levels in
      edible plant tissues and conversely increasing Cd accumulation in plants used for
      phytoremediation. Phytosiderophores are iron chelators excreted by graminaceous
      plants under conditions of iron limitation, but they also complex other metals
      including cadmium. Here we examine the influence of Cd exposure on
      phytosiderophore production by hydroponically grown maize. Cd increased the rate
      of the phytosiderophore 2'-deoxymugineic acid (DMA) release under both Fe
      sufficient and Fe-limiting conditions (+/-Fe). In addition, the -Fe plants
      released more DMA while taking up less Cd than the +Fe plants. In other short
      term Cd uptake experiments, plants exposed to Cd in the presence of root exudates
      in which the DMA-Cd complex was likely the dominant Cd species displayed reduced
      Cd accumulation in root tissue, and plants similarly exposed to strongly chelated
      Cd in the presence of EDTA (employed as a positive control) contained the least
      Cd. Collectively, these results indicate that Cd stress causes Fe deficiency
      symptoms that result in greater DMA production by maize roots, and then the DMA
      appears to reduce Cd accumulation.

PMID- 12521163
TI  - Significance of kinetics for sorption on inorganic colloids: modeling and
      experiment interpretation issues.
AB  - A two-site kinetic model for solute sorption on inorganic colloids is developed.
      The model quantifies linear first-order sorption on two types of sites ("fast"
      and "slow") characterized by two pairs of rates (forward and reverse). We use the
      model to explore data requirements for long-term predictive calculations of
      colloid-facilitated transport and to evaluate laboratory kinetic sorption data of
      Lu et al.. Five batch sorption data sets are considered with plutonium as the
      tracer and montmorillonite, hematite, silica, and smectite as colloids. Using
      asymptotic results applicable on the time scale of limited duration experiments,
      a robust estimation procedure is developed for the fast-site partitioning
      coefficient K(C) and the slow forward rate alpha. The estimated range of K(C) is
      1.1-76 L/g, and the range for alpha is 0.0017-0.02 1/h. The fast reverse rate
      k(r) is estimated in the range 0.012-0.1 1/h. Comparison of one-site and two-site
      sorption interpretations reveals the difficulty in discriminating between the two
      models for montmorillonite and to a lesser extent for hematite. For silica and
      smectite, the two-site model clearly provides a better representation of the data
      as compared with a single site model. Kinetic data for silica are available for
      different colloid concentrations (0.2 g/L and 1 g/L). For the range of
      experimental conditions considered, alpha appears to be independent of colloid
      concentration.

PMID- 12521164
TI  - Source apportionment of secondary airborne particulate matter in a polluted
      atmosphere.
AB  - Secondary airborne particulate matter formed from gas-phase pollutants
      contributes significantly to the most severe particulate air quality events that
      occur in the United States each year. In this study, a mechanistic air quality
      model is demonstrated that can predict source contributions to the size
      distribution of secondary airborne particulate matter. Calculations performed for
      a typical air quality episode in Southern California show that NOx released from
      diesel engines and catalyst-equipped gasoline engines account for the majority of
      the secondary particulate nitrate aerosol measured at inland locations. NH3
      released from catalyst-equipped gasoline engines, farm animals, and residential
      sources account for the majority of the secondary particulate ammonium ion at
      inland locations in the region. When both tailpipe and road dust emissions are
      considered, transportation sources dominate the size distribution of total
      (primary plus secondary) airborne particulate matter in the South Coast Air Basin
      during the episode studied. These findings suggest that the public health risk
      associated with air pollution released from transportation sources is significant
      relative to other public health threats such as traffic accidents.

PMID- 12521165
TI  - Effectiveness and reliability of arsenic field testing kits: are the million
      dollar screening projects effective or not?
AB  - The exposure of millions to arsenic contaminated water from hand tube wells is a
      major concern in many Asiatic countries. Field kits are currently used to
      classify tube wells as delivering arsenic below 50 microg/L (the recommended
      limit in developing countries) as safe, painted green or above 50 microg/L,
      unsafe and painted red. More than 1.3 million tube wells in Bangladesh alone have
      been tested by field kits. A few million U.S. dollars have already been spent and
      millions are waiting for the ongoing projects. However, the reliability of the
      data generated through field kits is now being questioned. Samples from 290 wells
      were tested by field kits and by a reliable laboratory technique to ascertain the
      reliability of field kits. False negatives were as high as 68% and false
      positives up to 35%. A statistical analysis of data from 240 and 394 other wells
      yielded similar rates. We then analyzed 2866 samples from previously labeled
      wells and found 44.9% mislabeling in the lower range (<50 microg/L) although
      mislabeling was considerably reduced in the higher range. Variation of analytical
      results due to analysts and replicates were pointed out adopting analysis of
      variance (ANOVA) technique. Millions of dollars are being spent without
      scientific validation of the field kit method. Facts and figures demand improved,
      environmentally friendly laboratory techniques to produce reliable data.

PMID- 12521166
TI  - Comparison of inductively coupled plasma-mass spectrometry and radiochemical
      techniques for total uranium in environmental water samples.
AB  - Inductively coupled plasma-mass spectrometry (ICP-MS) method EPA 200.8 is
      gradually finding acceptance as an alternative to uranium analysis. A comparison
      of the ICP-MS with the accepted radiochemical method EPA 908.0 has been carried
      out based on data from laboratory control standards, national proficiency test
      samples, and environmental and drinking water samples from the State of Utah. The
      method detection limit (MDL) for ICP-MS was determined to be 0.017 microg/L or
      (0.011 pCi/L), and the minimum reporting limit (MRL) was 0.17 microg/L (MDL x 10)
      or (0.11 pCi/L). The minimum reporting limit for radiochemical 908.0 method is 1
      pCi/L. Our spiked matrix recoveries, spiked blank samples, and reference
      materials deviate only a few percentage from the listed true values. Results
      demonstrate that the ICP-MS is a superior analytical tool for the determination
      of uranium in drinking and environmental waters at concentrations required by the
      United States Environmental Protection Agency.

PMID- 12521167
TI  - Bioconcentration of organic chemicals: is a solid-phase microextraction fiber a
      good surrogate for biota?
AB  - When organic chemicals are extracted from a water sample with solid-phase
      microextraction (SPME) fibers, the resulting concentrations in exposed fibers are
      proportional to the hydrophobicity of the compounds. This fiber accumulation is
      analogous to the bioconcentration of chemicals observed in aquatic organisms. The
      objective of this study was to investigate the prospect of measuring the total
      concentration in SPME fibers to estimate the total body residue in biota for the
      purpose of risk assessment. Using larvae of the midge, Chironomus riparius and
      disposable 15-microm poly(dimethylsiloxane) fibers, we studied the accumulation
      and accumulation kinetics of a number of narcotic compounds with a range of log
      K(ow) between 3 and 6. The fibers, which have a larger surface area-to-volume
      ratio, had consistently higher uptake and elimination rate constants (k1 and k2,
      respectively) than midge larvae and accumulated the chemicals 5 times faster.
      Comparison of the relationships of the partition coefficients K(PDMS-water) and
      K(midge-water) (lipid-normalized) to log K(ow) for all compounds yielded a factor
      of 28 for translating fiber concentrations to biota concentrations. This factor
      can be used to estimate internal concentrations in biota for compounds
      structurally similar to the compounds in this study. The exact chemical domain to
      which this factor can be applied needs to be defined in future research.

PMID- 12521168
TI  - Levels and sources of personal inhalation exposure to volatile organic compounds.
AB  - Personal exposures to VOCs of 12 urban dwellers were measured directly via
      personal monitoring and indirectly via static monitoring combined with personal
      activity diaries. Over 5-10 days, day-to-day variations in personal exposures of
      individuals were substantial, with statistically significant (p<0.05) deviation
      from the normal distribution observed for daily exposures to one or more VOCs for
      several subjects. Daytime concentrations generally exceeded night time, with
      day:night mean concentration ratios for each sampling day >1 for most VOCs, with
      the maximum (3.85) occurring for 1,3-butadiene. Exposure in the home contributed
      50-80% of overall individual exposure to 1,3-butadiene and benzene. For most
      VOCs, while absolute values of direct and indirect exposure estimates were
      significantly different (p<0.05), linear regression of direct and indirect
      exposure estimates revealed statistically significant correlation (p<0.01),
      confirming previous observations that indirect monitoring can provide
      satisfactory estimates of personal inhalation exposure to VOCs. ETS, the use of
      vehicles, and heating (but not cooking) all made appreciable contributions to
      personal exposure to all target VOCs.

PMID- 12521169
TI  - Selective trace analysis of sulfonylurea herbicides in water and soil samples
      based on solid-phase extraction using a molecularly imprinted polymer.
AB  - A molecularly imprinted polymer (MIP) was synthesized using the herbicide
      metsulfuron-methyl (MSM) as a template, 2-(trifluoromethyl)acrylic acid as a
      functional monomer, divinylbenzene as a cross-linker, and dichloromethane as a
      porogen. This polymer was used as a solid-phase extraction material for the
      quantitative enrichment of five sulfonylureas (nicosulfuron, thifensulfuron
      methyl, metsulfuron-methyl, sulfometuron-methyl, and chlorsulfuron) in natural
      water and soil samples and off-line coupled to a reversed-phase HPLC/diode array
      detection (HPLC/DAD). Washing solvent was optimized in terms of kind and volume
      for removing the matrix constituents nonspecifically adsorbed on the MIP. It has
      been shown that the nonspecific binding ability of the sulfonylureas to the
      polymer largely increased along with increasing the concentration of Ca2+ ions in
      the water sample, whereas complexation of divalent ions with EDTA eliminated this
      interference completely. The stability of MIP was tested by consecutive
      percolation of water sample, and it was shown that the performance of the MIP did
      not vary even after 200 enrichment and desorption cycles. Recoveries of the five
      sulfonylureas extracted from 1 L of tap water and surface water samples such as
      river water and rainwater at a 50 ng/L spike level were not lower than 96%. The
      recoveries of sulfonylureas extracted from 10-g soil sample at the 50 microg/kg
      level were in the range of 71-139%. Depending on the particular compound, the
      limit of detection varied from 2 to 14 ng/L in water and from 5 to 12 microg/kg
      in soil samples. The MIP was also compared with a commercially available C-18
      column and an immunoaffinity support with encapsulated polyclonal anti-MSM
      antibodies in sol-gel glass.

PMID- 12521170
TI  - Fractionation and determination of aluminum and iron in soil water samples using
      SPE cartridges and ICP-AES.
AB  - The use of commercially available solid phase extraction (SPE) cartridges for the
      fractionation of Al and Fe in soil water is described. The quantitative
      determination was done by inductively coupled plasma atomic emission spectrometry
      (ICP-AES). Different types of SPE cartridges, based on cation exchange, anion
      exchange, and chelation were studied. To avoid pH changes, the SPE cartridge
      should be conditioned with a buffer that has a pH close to that of the sample.
      Both strong cation exchange (SCX) and chelation were found to work well, whereas
      low recovery was observed for Al when anion exchange was used. For Fe, the sum of
      the anionic and cationic fractions that passed through the cartridges was nearly
      100%. The results obtained for Al for 23 soil water samples using a SPE/SCX
      cartridge and ICP-AES were compared with equilibrium calculations using the
      program ALCHEMI and also with a fractionation method that was based on separation
      on a manually prepared SCX column and detection by molecular spectrophotometry,
      after complexation with pyrocatechol violet (SCX-PCV method). The SPE/SCX-ICP-AES
      results for the labile Al fraction (Al bound to the SCX cartridge) showed an
      acceptable correlation with the results obtained by the equilibrium calculations,
      except for the samples with the highest DOC concentrations, whereas the values
      obtained for labile Al by the more traditional SCX-PCV method were much lower. We
      recommend that the SPE/SCX-ICP-AES procedure described in this work be selected
      for the fractionation of Al and Fe species in soil and freshwater samples.

PMID- 12521171
TI  - Conductivity reduction due to emulsification during surfactant enhanced-aquifer
      remediation. 1. Emulsion transport.
AB  - Surfactant-enhanced aquifer remediation (SEAR) is a promising technology for the
      remediation of subsurface zones contaminated with organic liquids. To ensure the
      success of SEAR, the potential reduction in hydraulic conductivity must be
      evaluated. The objective of this study was to examine the process of conductivity
      reduction due to the transport of an emulsion, generated by mixing
      tetrachloroethylene with 4% solutions of two nonionic surfactants, in packed beds
      of sand-sized silica particles. The injection of the emulsion resulted in a 75
      85% reduction in conductivity, depending on the properties of the surfactant and
      the porous medium. The greater viscosity of the emulsion relative to that of
      water accounted for about 25% of the reduction. The remainder was attributed to
      the clogging of the porous medium by the emulsion. The relative sizes of the
      emulsion droplets and the packed bed's pores, coupled with measurements of zeta
      potential of the emulsion droplets and silica particles, suggested that
      multilayer deposition was the principal mechanism of clogging. This hypothesis
      was corroborated by direct observation of the emulsion transport process in a
      micromodel. To simulate the reduction in hydraulic conductivity in these systems
      accurately, it was necessary to modify the emulsion transport model by Soo and
      Radke to include the phenomena of viscosity variation and multilayering.

PMID- 12521172
TI  - Conductivity reduction due to emulsification during surfactant enhanced-aquifer
      remediation. 2. Formation of emulsion in situ.
AB  - Permeability reduction due to surfactant emulsification can impact the
      effectiveness of surfactant-enhanced aquifer remediation (SEAR). The objective of
      this study was to examine the process of in situ emulsification in systems
      composed of tetrachloroethylene (PCE) and solutions of two nonionic surfactants
      selected for their ability to enhance solubility. The injection of the surfactant
      solutions into columns packed with sand-sized silica particles containing
      residual saturations of PCE resulted in the formation of an emulsion with an
      average droplet diameter of 0.1-0.2 microm, about an order of magnitude smaller
      than that of the ex situ formed emulsion. The measurements of hydraulic
      conductivity showed an initial decrease, followed by a gradual increase, with a
      final steady-state reduction of about 35% after the injection of 7-8 pore volumes
      of surfactant solution, of which about 8% could be attributed to the deposition
      of the emulsion. To describe the observed trends, the modified emulsion transport
      model from Part 1 was modified to include the processes of the formation of the
      emulsion and the reduction of the PCE residual. The good comparison between the
      simulations and the experimental data suggests that the model correctly reflects
      the multiple processes controlling the hydraulic conductivity of the packed
      columns during surfactant solution injection.

PMID- 12521173
TI  - Experimental determination of the fate of rising CO2 droplets in seawater.
AB  - Direct oceanic disposal of fossil fuel CO2 is being considered as a possible
      means to moderate the growth rate of CO2 in the atmosphere. We have measured the
      rise rate and dissolution rate of freely released CO2 droplets in the open ocean
      to provide fundamental data for carbon sequestration options. A small amount of
      liquid CO2 was released at 800 m, at 4.4 degrees C, and the rising droplet stream
      was imaged with a HDTV camera carried on a remotely operated vehicle. The initial
      rise rate for 0.9-cm diameter droplets was 10 cm/s at 800 m, and the dissolution
      rate was 3.0 micromol cm(-2) s(-1). While visual contact was maintained for 1 h
      and over a 400 m ascent, 90% of the mass loss occurred within 30 min over a 200 m
      ascent above the release point. Images of droplets crossing the liquid-gas-phase
      boundary showed formation of a gas head, pinching off of a liquid tail, and rapid
      gas bubble separation and dissolution.

PMID- 12521174
TI  - Development of a kinetic model for the NOx reduction process by potassium
      containing coal pellets.
AB  - A four step kinetic model was developed to describe the NOx reduction process by
      potassium containing coal-pellets. The relevance and significance of the
      different steps considered in the model as well as the considerations assumed to
      introduce the equations associated to this model were properly discussed. The
      simulation both of the NOx reduction and carbon conversion evolution shows good
      agreement with the experimental data obtained throughout lifetime tests at 350
      degrees C for samples with different potassium contents. The set of parameters
      predicted by the kinetic model have physical significance and are helpful in
      explaining the different behavior exhibited by the samples. Some of these
      parameters can be correlated with different features of the samples. The
      potassium loading influences mainly on the kinetic rate constant governing the
      NOx chemisorption step, thus explaining the increase in selectivity with the
      catalyst content exhibited by this type of samples.

PMID- 12521175
TI  - Arsenic(III) and arsenic(V) reactions with zerovalent iron corrosion products.
AB  - Zerovalent iron (Fe0) has tremendous potential as a remediation material for
      removal of arsenic from groundwater and drinking water. This study investigates
      the speciation of arsenate (As(V)) and arsenite (As(III)) after reaction with two
      Fe0 materials, their iron oxide corrosion products, and several model iron
      oxides. A variety of analytical techniques were used to study the reaction
      products including HPLC-hydride generation atomic absorption spectrometry, X-ray
      diffraction, scanning electron microscopy-energy-dispersive X-ray analysis, and X
      ray absorption spectroscopy. The products of corrosion of Fe0 include
      lepidocrocite (gamma-FeOOH), magnetite (Fe3O4), and/or maghemite (gamma-Fe2O3),
      all of which indicate Fe(II) oxidation as an intermediate step in the Fe0
      corrosion process. The in-situ Fe0 corrosion reaction caused a high As(III) and
      As(V) uptake with both Fe0 materials studied. Under aerobic conditions, the Fe0
      corrosion reaction did not cause As(V) reduction to As(III) but did cause As(III)
      oxidation to As(V). Oxidation of As(III) was also caused by maghemite and
      hematite minerals indicating that the formation of certain iron oxides during Fe0
      corrosion favors the As(V) species. Water reduction and the release of OH- to
      solution on the surface of corroding Fe0 may also promote As(III) oxidation.
      Analysis of As(III) and As(V) adsorption complexes in the Fe0 corrosion products
      and synthetic iron oxides by extended X-ray absorption fine structure
      spectroscopy (EXAFS) gave predominant As-Fe interatomic distances of 3.30-3.36 A.
      This was attributed to inner-sphere, bidentate As(III) and As(V) complexes. The
      results of this study suggest that Fe0 can be used as a versatile and economical
      sorbent for in-situ treatment of groundwater containing As(III) and As(V).

PMID- 12521176
TI  - Selective photocatalytic oxidation of NH3 to N2 on platinized TiO2 in water.
AB  - Selective photocatalytic oxidation of NH3 to N2 is proposed as a new treatment
      method for controlling the levels of ammonia in water. The photocatalytic
      oxidation of ammonia on naked and metallized TiO2 in water saturated with air,
      nitrogen, or NO2 gas was investigated. While the slow photocatalytic oxidation of
      NH3 to NO2-/NO3- is the only pathway for decomposition of NH3 on naked TiO2 and
      Au/TiO2, a new pathway, that of selective oxidation of ammonia to dinitrogen,
      opens up on Pt/TiO2. The formation of dinitrogen from the oxidation of 15NH3 was
      confirmed by mass spectrometric detection of 15N2. The photocatalytic conversion
      of NH3 to N2 greatly increases when the Pt/TiO2 suspension is saturated with NO2
      gas, whereas NO2 itself shows little reactivity with naked TiO2 and Au/TiO2. Over
      80% of the total nitrogen available in ammonia (0.1 mM) is converted into N2
      within 40 min illumination of the N2O-saturated Pt/TiO2 suspension. The ability
      of N2O to accept the conduction band electrons of Pt/TiO2 was verified by
      photoelectrochemical measurements. NO2 reductively decomposes to generate OH
      radicals on Pt/TiO2; the rate of ammonia degradation in the NO2-saturated Pt/TiO2
      suspension significantly decreases in the presence of excess tert-butyl alcohol,
      an OH radical scavenger. The presence of Pt deposits on the TiO2 particles
      changes the photocatalytic pathway of ammonia conversion by both enhancing OH
      radical production from NO2 and stabilizing intermediate NHx (x=0, 1, 2) species
      to facilitate their recombination into N2.

PMID- 12521177
TI  - Formation of ferrihydrite and associated iron corrosion products in permeable
      reactive barriers of zero-valent iron.
AB  - Ferrihydrite, which is known to form in the presence of oxygen and to be
      stabilized by the adsorption of Si, PO4 and SO4, is ubiquitous in the fine
      grained fractions of permeable reactive barrier (PRB) samples from the U.S. Coast
      Guard Support Center (Elizabeth City, NC) and the Denver Federal Center
      (Lakewood, CO) studied by high-resolution transmission electron microscopy and
      selected area electron diffraction. The concurrent energy-dispersive X-ray data
      indicate a strong association between ferrihydrite and metals such as Si, Ca, and
      Cr. Magnetite, green rust 1, aragonite, calcite, mackinawite, greigite and
      lepidocrocite were also present, indicative of a geochemical environment that is
      temporally and spatially heterogeneous. Whereas magnetite, which is known to form
      due to anaerobic Fe0 corrosion, passivates the Fe0 surface, ferrihydrite
      precipitation occurs away from the immediate Fe0 surface, forming small (<0.1
      microm) discrete clusters. Consequently, Fe0-PRBs may remain effective for a
      longer period of time in slightly oxidized groundwater systems where ferrihydrite
      formation occurs compared to oxygen-depleted systems where magnetite passivation
      occurs. The ubiquitous presence of ferrihydrite suggests that the use of Fe0-PRBs
      may be extended to applications that require contaminant adsorption rather than,
      or in addition to, redox-promoted contaminant degradation.

PMID- 12521178
TI  - Understanding chromate reaction kinetics with corroding iron media using Tafel
      analysis and electrochemical impedance spectroscopy.
AB  - The kinetics of chromate removal from contaminated water by zerovalent iron media
      are not well understood. This study investigated the reactions occurring on iron
      surfaces in chromate solutions in order to understand the removal kinetics and to
      assess the long-term ability of zerovalent iron for removing Cr(VI) from
      contaminated water. Tafel polarization analysis and electrochemical impedance
      spectroscopy were used to determine the corrosion rates and charge-transfer
      resistances associated with Cr(VI) removal by iron wires suspended in electrolyte
      solutions with initial Cr(VI) concentrations of 10,000 microg/L. The condition of
      the iron surfaces at the time of their exposure to chromate determined the
      effectiveness of the iron for chromate removal. Both iron coated with a water
      formed oxide and initially oxide-free iron were effective for chromate removal.
      However, iron coated with an air-formed oxide was an order of magnitude less
      effective for removing soluble chromium. Although iron with the air-formed oxide
      was largely passivated with respect to chromate removal, its overall rate of
      corrosion was similar to that for iron with the other initial surface conditions.
      This indicates that water, but not chromate, was able to penetrate the air-formed
      oxide coating and access cathodic sites. For all initial surface conditions,
      addition of chromate decreased the corrosion rate by increasing the corrosion
      potential and the anodic charge transfer resistance. Although Cr(VI) is a strong
      oxidant rates of iron corrosion were not proportional to the aqueous Cr(VI)
      concentrations due to anodic control of iron corrosion. Under anodically
      controlled conditions, the rate of corrosion was limited by the rate at which
      Fe2+ could be released at anodic sites and not by the rate at which oxidants were
      able to accept electrons. This study shows that the zero order removal kinetics
      of Cr(VI) by iron media can be explained by anodic control of iron corrosion and
      the concomitant anodic control of Cr(VI) reduction.

PMID- 12521179
TI  - Influence of heterotrophic microbial growth on biological oxidation of pyrite.
AB  - The rate and extent of pyrite oxidation by the iron-oxidizing bacteria
      Acidithiobacillus ferrooxidans was limited by the growth of the heterotrophic
      microbe Acidiphilium acidophilum. In batch systems containing a mixture of both
      organisms, the maximum zero-order rate of ferric iron accumulation was about 1.4
      mg of Fe3+ L(-1) d(-1) as compared to 9.4 mg of Fe3+ L(-1) d(-1) for pure
      cultures of A. ferrooxidans under the same conditions. Pyrite oxidation was
      limited in cases where both cultures of organisms were initially present as well
      as situations where the heterotrophic organisms were added to established, pyrite
      oxidizing systems containing A. ferrooxidans. Results also indicated that organic
      carbon remaining in solution following heterotrophic bacterial growth reduced the
      rate of abiotic pyrite oxidation by the ferric ion. Furthermore, a cell-free
      solution of the residual organic carbon resulted in a lag of A. ferrooxidans
      growth in soluble ferrous medium. The residual organic carbon solution that
      accumulated during the growth of Aph. acidophilum had a diverse molecular weight
      distribution, indicating that different compounds could be responsible for the
      inhibition of chemical pyrite oxidation and the A. ferrooxidans growth lag
      observed. Titration of dissolved copper ions with residual dissolved organic
      carbon originating from Aph. acidophilum cultures indicated that a metal
      complexation mechanism could be responsible for the lower rates of pyrite
      oxidation observed. These data suggest that encouraging the growth of
      heterotrophic microorganisms under acid mine drainage conditions may be a
      feasible strategy for decreasing both the rate and the extent of sulfide mineral
      oxidation.

PMID- 12521180
TI  - Laboratory evaluation of custom-designed surfactants to remediate NAPL source
      zones.
AB  - Laboratory column studies were conducted using custom-designed anionic
      surfactants, the branched alcohol propoxylated sulfates, to evaluate their
      effectiveness in removing nonaqueous phase liquids (NAPLs) from both Ottawa sand
      and field alluvium. Surfactant efficacy was tested at temperatures ranging
      between 11 and 50 degrees C for contaminants such as tetrachloroethene (PCE),
      weathered gasoline, and Naval Special Fuel Oil. It has been shown that use of
      branched alcohol propoxylated sulfates can achieve very low final NAPL
      saturations even with recalcitrant NAPLs, while exhibiting low induced hydraulic
      gradients, low microemulsion viscosity, and minimal sorption on contaminated
      field soils. These custom-designed surfactants are effective with both dense
      NAPLs (DNAPLs) and light NAPLs. Finally, these surfactants were used to create
      neutrally buoyant microemulsions with a PCE DNAPL. The laboratory experiments
      show that these custom-designed, high-performance surfactants can be tailored to
      optimize contaminant solubility for specific field NAPLs.

PMID- 12521181
TI  - Nitric oxide reduction in coal combustion: role of char surface complexes in
      heterogeneous reactions.
AB  - Nitrogen oxides are one of the major environmental problems arising from fossil
      fuel combustion. Coal char is relatively rich in nitrogen, and so this is an
      important source of nitrogen oxides during coal combustion. However, due to its
      carbonaceous nature, char can also reduce NO through heterogeneous reduction. The
      objectives of this work were on one hand to compare NO emissions from coal
      combustion in two different types of equipment and on the other hand to study the
      influence of char surface chemistry on NO reduction. A series of combustion tests
      were carried out in two different scale devices: a thermogravimetric analyzer
      coupled to a mass spectrometer and an FTIR (TG-MS-FTIR) and a fluidized bed
      reactor with an on line battery of analyzers. The TG-MS-FTIR system was also used
      to perform a specific study on NO heterogeneous reduction reactions using chars
      with different surface chemistry. According to the results obtained, it can be
      said that the TG-MS-FTIR system provides valuable information about NO
      heterogeneous reduction and it can give good trends of the behavior in other
      combustion equipments (i.e., fluidized bed combustors). It has been also pointed
      out that NO-char interaction depends to a large extent on temperature. In the low
      temperature range (<800 degrees C), NO heterogeneous reduction seems to be
      controlled by the evolution of surface complexes. In the high-temperature range
      (>800 degrees C), a different mechanism is involved in NO heterogeneous
      reduction, the nature of the carbon matrix being a key factor.

PMID- 12521182
TI  - The 1.7 kilogram microchip: energy and material use in the production of
      semiconductor devices.
AB  - The scale of environmental impacts associated with the manufacture of microchips
      is characterized through analysis of material and energy inputs into processes in
      the production chain. The total weight of secondary fossil fuel and chemical
      inputs to produce and use a single 2-gram 32MB DRAM chip are estimated at 1600 g
      and 72 g, respectively. Use of water and elemental gases (mainly N2) in the
      fabrication stage are 32,000 and 700 g per chip, respectively. The production
      chain yielding silicon wafers from quartz uses 160 times the energy required for
      typical silicon, indicating that purification to semiconductor grade materials is
      energy intensive. Due to its extremely low-entropy, organized structure, the
      materials intensity of a microchip is orders of magnitude higher than that of
      "traditional" goods. Future analysis of semiconductor and other low entropy high
      tech goods needs to include the use of secondary materials, especially for
      purification.

PMID- 12521184
TI  - How green is a chemical reaction? Application of LCA to green chemistry.
AB  - In the present work Life Cycle Assessment (LCA) is used in order to evaluate a
      chemical reaction from an environmental point of view. The objective is to assess
      the usefulness of this methodology as an environmental tool to be applied to
      green chemistry. As an example, two routes of obtaining maleic anhydride are
      compared using LCA, to ascertain which one is the most environmentally friendly.
      From the results obtained in this work it can be concluded that LCA seems to be a
      valuable tool for the environmental assessment of a chemical reaction, because it
      takes into account all the life cycle stages of the process and discusses the
      impact of the environmental burdens inventoried according to a diversity of
      impact categories.

PMID- 12521183
TI  - Green technology for conversion of food scraps to biodegradable thermoplastic
      polyhydroxyalkanoates.
AB  - A new technology is developed and demonstrated that couples anaerobic digestion
      of food scraps with production of biodegradable thermoplastics,
      polyhydroxyalkanoates (PHAs). The food wastes were digested in an anaerobic
      reactor producing four major organic acids. The concentrations of acetic,
      propionic, butyric, and lactic acids reached 5.5, 1.8, 27.4, and 32.7 g/L,
      respectively. The fermentative acids were transferred through membranes via
      molecule diffusion into an air-bubbling reactor where the acids were utilized to
      produce PHAs in an enriched culture of Ralstonia eutropha. With a silicone rubber
      membrane, butyric acid and small amounts of acetic and propionic acids were
      transferred and used, producing a homopolymer PHA, poly(3-hydroxybutyrate). The
      dry cell weight and PHA content reached 11.3 g/L and 60.2% (w/w), respectively.
      With a dialysis membrane, the mass transfer rates of fermentative acids were
      enhanced, and the PHA production was significantly improved. The dry cell weight
      and its PHA content reached 22.7 g/L and 72.6% (w/w), respectively. The formed
      PHA was a copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate (HV) with 2.8 mol
      % HV monomer unit. The polymer content (72.6% of dry cell mass) reported in this
      study is the highest one obtained from organic wastes and is comparable with the
      PHA content from pure glucose fermentation.

PMID- 12521185
TI  - Hyperesthesia: an early manifestation of diabetic polyneuropathy.

PMID- 12521186
TI  - Fungal infection: relation with cerebrovascular disease during chemotherapy for
      acute leukemia.

PMID- 12521187
TI  - Ursodeoxycholic acid as an alternative therapy for autoimmune pancreatitis.

PMID- 12521188
TI  - Familial hypocalciuric hypercalcemia.

PMID- 12521189
TI  - Does IL-6 mediate renal manifestations of Castleman's disease?

PMID- 12521190
TI  - Renal involvement in sarcoidosis.

PMID- 12521191
TI  - Development of treatment for pulmonary alveolar proteinosis.

PMID- 12521192
TI  - Chronic myelogenous leukemia with p190BCR-ABL expression: the missing link with
      monocytosis.

PMID- 12521193
TI  - Headache and spontaneous vertebral artery dissection.

PMID- 12521194
TI  - Clinical significance of anti-Ku autoantibodies--a serologic marker of overlap
      syndrome?

PMID- 12521195
TI  - Asian variant of intravascular large B-cell lymphoma: still a diagnostic enigma?

PMID- 12521196
TI  - Procerus sign in progressive supranuclear palsy and corticobasal degeneration.

PMID- 12521197
TI  - Clinical analysis of pulmonary tuberculosis in association with corticosteroid
      therapy.
AB  - OBJECTIVE: Due to the increased incidence of pulmonary tuberculosis in
      association with corticosteroid therapy during the last five years in our
      associated hospitals, we studied the clinical characteristics of these patients.
      PATIENTS: Fourteen cases of pulmonary tuberculosis were collected which occurred
      in association with corticosteroid drugs in our associated hospitals during the
      last 10 years; four patients (2.1%) from April 1991 to March 1996 and 10 patients
      (4.3%) from April 1996 to March 2001. RESULTS: The average age of the 14 patients
      was 74.1 years old and the male:female ratio was 9:5. Regarding underlying
      diseases, respiratory diseases (7 patients) were the most frequent and a past
      history of pulmonary tuberculosis was recognized in six patients. The duration of
      corticosteroid administration ranged from two months to seven years and the total
      dose of corticosteroids ranged from 1.20 g to 12.05 g. Pulmonary tuberculosis was
      detected by chance during a health examination in eight patients and radiological
      findings showed an infiltration shadow without cavity located in a portion other
      than the predominant location in four patients. A microbiological examination was
      smear positive in eight patients but tolerance was not shown to any
      antituberculous drugs. The prognosis was poor because the mortality rate was
      high, but the cause of death was not related to the progress of pulmonary
      tuberculosis. CONCLUSION: Careful observation of patients is considered to be
      important because pulmonary tuberculosis in association with corticosteroid drugs
      was found among inpatients, there was no relationship to the total dose or
      duration of administration of corticosteroid drugs, there were no clinical
      symptoms, and the patients exhibited atypical radiographic findings.

PMID- 12521198
TI  - Welder's pneumoconiosis: diagnostic usefulness of high-resolution computed
      tomography and ferritin determinations in bronchoalveolar lavage fluid.
AB  - OBJECTIVE: We assessed the usefulness of high-resolution computed tomography
      (HRCT) and ferritin determinations in bronchoalveolar lavage (BAL) fluid for
      diagnosis of welder's pneumoconiosis. PATIENTS AND METHODS: We investigated 11
      patients with welder's pneumoconiosis who were 34 to 67 years old and had been
      welding for 17 to 45 years. Ten patients were current smokers. We performed chest
      radiography and HRCT, and measured serum ferritin on all 11 patients. We obtained
      BAL fluid in 9 cases and transbronchial lung biopsy (TBLB) specimens in 7.
      Ferritin concentrations in BAL fluid were compared with those in welders without
      pneumoconiosis and other pneumoconiosis cases. RESULTS: HRCT revealed small
      centrilobular nodules in 9 cases, mild fibrotic changes in 3, and emphysematous
      changes in 3. Serum ferritin concentrations were elevated (>240 ng/ml) in 10
      cases. Ferritin concentrations in BAL fluid were higher in welder's
      pneumoconiosis than in the occupational control group. CONCLUSION: In welder's
      pneumoconiosis, small centrilobular nodules are frequently seen on HRCT, and
      ferritin shows elevations in serum and/or BAL fluid. Such ferritin determinations
      are of value in diagnosis.

PMID- 12521199
TI  - Open-label compassionate use one year-treatment with pirfenidone to patients with
      chronic pulmonary fibrosis.
AB  - OBJECTIVE: We attempted to evaluate the feasibility (therapeutic efficacy,
      tolerance, and clinical courses after treatment) of pirfenidone, an anti-fibrotic
      drug for patients with chronic pulmonary fibroses such as idiopathic pulmonary
      fibrosis (IPF). METHODS: Open-label one-year treatment for compassionate-use.
      PATIENTS OR MATERIALS: Oral pirfenidone (40 mg/kg body weight) was administered
      to 8 patients with advanced IPF and 2 with interstitial pneumonia associated with
      diffuse systemic sclerosis. The plasma concentration of the drug was serially
      followed. Radiographic scores, pulmonary functions, and arterial blood oxygen
      pressure were compared at three time points: at one-year before treatment, at the
      time of entry, and at one-year after entry. RESULTS: While pirfenidone did not
      show a definite therapeutic effect on overall survival (2 years after entry).
      During one-year treatment, there was no significant deterioration in terms of
      chest radiographic scores and arterial oxygen pressure, and the drug was well
      tolerated with minimal adverse effects within the ranges observed in this study,
      plasma pirfenidone concentrations did not seem to relate to the appearance of
      adverse effects or differences in therapeutic effects. CONCLUSION: The
      feasibility of Pirfenidone as a therapeutic drug was confirmed for patients with
      advanced pulmonary fibrosis.

PMID- 12521200
TI  - Prevalence of hyperesthesia detected by current perception threshold test in
      subjects with glucose metabolic impairments in a community.
AB  - OBJECTIVE: Recent studies reported that hyperesthesia may be an indicator of
      early diabetic polyneuropathy. Using the current perception threshold (CPT) test,
      which stimulates peripheral sensory nerve fibers by three different frequencies
      (2,000, 250, and 5 Hz), we investigated the relationship between hyperesthesia
      and glucose metabolic impairment in a community. METHODS: The number of subjects,
      aged 40 to 79 years, was 2,074. The CPT values at each frequency were classified
      into three categories (hyperesthesia, normal, and hypoesthesia). Subjects were
      also subgrouped into three groups (normal, insulin resistance, and diabetes)
      according to glucose metabolic status, and those with hypoesthesia at each
      frequency were excluded in the analyses. RESULTS: The prevalence of hyperesthesia
      at 2,000, 250, and 5 Hz in male diabetic subjects were 14.1, 15.6, and 7.7%,
      respectively, and 22.2, 24.5, and 16.4% respectively in female diabetic subjects.
      In logistic regression analysis adjusted for age, females with diabetes showed a
      significantly high odds ratio (OR) for hyperesthesia at 2,000 Hz (OR, 2.42; 95%
      confidence interval (95%CI), 1.18 to 4.97) and 250 Hz (OR, 2.65; 95%CI, 1.31 to
      5.37). In male diabetic subjects, a significantly high odds ratio for
      hyperesthesia was seen at 250 Hz (OR, 2.09; 95%CI, 1.07 to 4.05). CONCLUSION: Our
      results suggested that hyperesthesia may emerge coupled with developing diabetes,
      supporting the precedent hypothesis.

PMID- 12521201
TI  - Cerebrovascular disease in acute leukemia: a clinicopathological study of 14
      patients.
AB  - OBJECTIVE: Cerebrovascular disease (CVD) is a serious complication of acute
      leukemia, and the underlying conditions are different from the common risk
      factors for CVD. The aim of this study was to characterize the clinical and
      pathological features of CVD in patients with acute leukemia. PATIENTS OR
      MATERIALS: In our series of 116 autopsied cases of acute leukemia during the
      period between January 1978 and December 1998, we had 14 patients who had CVD
      during the course of acute leukemia. The neuropathological and clinical features
      of those patients were examined. RESULTS: Neuropathological examination showed
      hemorrhagic infarction due to disseminated aspergillosis or mucormycosis (5
      cases), multiple hemorrhages due to leukemic cell infiltration (2 cases) and a
      single massive hemorrhage with petechial hemorrhages in various regions of the
      brain (4 cases). Three patients had CVD due to miscellaneous causes.
      Clinicopathological correlation revealed that fungal disseminations occurred
      under agranulocytosis, while leukemic cell infiltration occurred under a marked
      leukocyotosis (peripheral white blood cell count >100,000/microl). Four patients
      with coagulopathy, including three with disseminated intravascular coagulation
      (DIC) had a single massive hemorrhage. CONCLUSION: Our study demonstrated that
      there were at least three types of CVD with specific clinicopathological
      features. Hemorrhagic infarction under agranulocyotosis was due to disseminated
      aspergillosis or mucormycosis. Multiple cerebral hemorrhages under marked
      leukocyotosis was due to leukemic cell infiltration into the brain. Massive
      cerebral hemorrhage was associated with coagulopathy including DIC.

PMID- 12521202
TI  - Chronological evaluation of the onset of histologically confirmed interstitial
      pneumonia associated with polymyositis/dermatomyositis.
AB  - OBJECTIVE: The present study was designed to determine the chronological sequence
      of interstitial pneumonia, skin involvement, and muscle involvement associated
      with polymyositis/dermatomyositis (PM/DM). METHODS: We examined our own cases of
      histologically confirmed interstitial pneumonia associated with PM/DM. In
      addition, a review of the literature was done to evaluate other cases of
      histologically confirmed interstitial pneumonia associated with PM/DM. Lung
      involvement was the first clinical symptom for all of our 8 patients. RESULTS:
      Including the literature review and our 8 cases, there were 94 patients with
      PM/DM in whom interstitial pneumonia was histologically confirmed (36 PM, 50 DM,
      and 8 amyopathic DM). Chronological evaluation between the diagnosis of PM/DM and
      lung involvement demonstrated that most lung involvement occurred just before or
      just after the diagnosis of PM/DM. Interstitial pneumonia was preceded in 35 of
      87 evaluable patients [21 cases with PM (61.8%), 14 cases with DM and amyopathic
      DM (40.2%)]. In 60 of 87 evaluable patients (69.0%), lung involvement occurred as
      a clinical manifestation at the diagnosis of PM/DM. CONCLUSION: The present data
      demonstrate that interstitial pneumonia was frequently the initial onset in
      patients with PM/DM.

PMID- 12521203
TI  - Autoimmune pancreatitis successfully treated with ursodeoxycholic acid.
AB  - A 51-year-old woman with autoimmune pancreatitis is reported in whom treatment
      with ursodeoxycholic acid (UDCA) was beneficial. Complaining of epigastric
      discomfort, she presented with liver dysfunction of the cholestatic type, and
      diabetes mellitus. Pancreatic imaging revealed a diffuse swelling of the body, an
      irregular narrowing of the main pancreatic duct, and a terminal stricture of the
      common bile duct. Histologically, the biopsied pancreas was replaced by fibrous
      tissue with a small amount of mononuclear cell infiltration. She had anti
      carbonic anhydrase-II antibody and anti-lactoferrin antibody. After treatment
      with UDCA, her liver dysfunction and diabetes mellitus improved and the pancreas
      size was reduced. Steroid therapy is usually indicated for this disorder, but
      UDCA may be given as an alternative choice.

PMID- 12521204
TI  - Normalization of left ventricular parameters following combined pimobendan and
      carvedilol treatment in a case of unclassified cardiomyopathy with longstanding
      refractory status.
AB  - A 58-year-old man with a 64-month history of unclassified cardiomyopathy
      developed congestive heart failure (CHF) and had been dependent on long-term
      intravenous positive inotropes. Combined pimobendan and carvedilol administration
      resulted in marked symptomatic improvement from New York Heart Association
      functional class IV to I. Echocardiograms showed improvement of left ventricular
      (LV) ejection fraction from 15 to 48%, and LV end-diastolic diameter from 6.7 to
      4.9 cm. This mode of therapy not only improved LV contractile function but also
      normalized LV volume, which was an unusual clinical course compared with the
      general course of advanced CHF.

PMID- 12521205
TI  - Marked hypercalcemia in a patient with hypocalciuric hypercalcemia without a
      mutation in the calcium-sensing receptor gene.
AB  - A 60-year-old man was admitted to our hospital with marked hypercalcemia. He had
      no symptoms that might be caused by hypercalcemia. Plasma concentrations of
      calcium and intact parathyroid hormone were 15.2 mg/dl and 103 pg/ml,
      respectively. Radiological examinations revealed no abnormal findings. His
      calcium-creatinine clearance ratio was calculated to be 0.004, thus he was
      diagnosed as having hypocalciuric hypercalcemia. Familial hypocalciuric
      hypercalcemia was a plausible diagnosis, however, gene analysis of his calcium
      sensing receptor (CaSR) revealed no mutation. The patient was thought to be a
      case of hypocalciuric hypercalcemia without mutation in the CaSR gene.

PMID- 12521206
TI  - Acute interstitial nephritis with polyclonal B cell infiltration and development
      of mantle cell lymphoma.
AB  - A 69-year-old man with proteinuria, hematuria and abnormal renal and hepatic
      function developed acute renal failure. His clinical and laboratory examinations
      showed splenomegaly, edema, anemia and polyclonal hypergammaglobulinemia with
      high IgG levels. Renal biopsy showed interstitial nephritis with predominant B
      cell and plasma cell infiltration without monoclonality. After corticosteroid
      treatment, the patient showed remission in clinical symptoms and laboratory
      findings. However, one year later, he developed mantle cell lymphoma (MCL) with
      typical lymphocyte markers of cyclin D1 and CD5. When evaluated retrospectively,
      this patient appeared to have multicentric Castleman's disease initially and
      developed MCL later.

PMID- 12521207
TI  - Gross hematuria rapidly deteriorated renal function in a patient with polycystic
      kidney disease and Klippel-Trenaunay-Weber syndrome.
AB  - A case of polycystic kidney disease (PKD) associated with Klippel-Trenaunay-Weber
      syndrome is described. A 58-year-old man with chronic renal failure experienced
      urinary retention following gross hematuria. Intermittent drainage was necessary
      for significant urination for five days. Thereafter his urinary retention was
      relieved, but renal failure progressively developed and hemodialysis was started.
      Right hydronephrisis and hydroureter disappeared one month later. In spite of
      relief of obstruction, of which the cause was likely blood clots, renal function
      was not restored. Obstructive nephropathy was most likely explicable for notable
      deterioration in renal function. Our case might have susceptibilities to PKD
      development in terms of angiogenesis.

PMID- 12521208
TI  - Progression of renal failure delayed by use of losartan in a case of IgA
      nephropathy.
AB  - We report a case of IgA nephropathy with renal failure in which the deterioration
      of renal function was inhibited by the addition of angiotensin II receptor
      blocker (ARB) losartan. Before administration of losartan, the mean decline in
      the patient's glomerular filtration rate (GFR) was 0.64 ml/min/1.73 m2/month.
      Losartan treatment was started when serum creatinine rose above 4.0 mg/dl. With
      this treatment the serum creatinine level has remained stable for 3.5 years, and
      the mean decline in GFR was 0.06 ml/min/1.73 m2/month. We document successful
      retardation of renal failure with the use of losartan. Our experience suggests
      that dialysis therapy can be delayed significantly in patients using this drug.

PMID- 12521210
TI  - Pulmonary alveolar proteinosis successfully treated with ambroxol.
AB  - A 79-year-old woman was admitted to hospital due to a four-month history of a
      cough and dyspnea on exertion. Chest CT scans revealed ground glass opacity with
      thickened interlobular septa in both lungs. Bronchoalveolar lavage fluid (BALF)
      had milky appearance and revealed large acellular eosinophilic amorphous bodies
      positively stained with periodic acid-Schiff (PAS). Autoantibodies against
      granulocyte-macrophage colony-stimulating factor (GM-CSF) were present in sera
      and BALF from the patient. Ambroxol was started in a daily dose of 45 mg orally.
      Her oxygen saturation improved and abnormal shadows in CT scan disappeared 6
      months after beginning the therapy.

PMID- 12521209
TI  - A patient with sarcoidosis presenting with acute renal failure: implication for
      granulomatous interstitial nephritis and hypercalcemia.
AB  - A woman was admitted for acute renal failure and erythematous lesions. She was
      diagnosed with sarcoidosis after analysis of biopsy specimens revealed
      noncaseating epithelioid granulomas, elevated serum angiotensin-converting enzyme
      levels, and bilateral hilar lymphadenopathy. Serum concentrations of ionized
      calcium and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] were extremely high. Serum
      intact osteocalcin concentration and urinary deoxypyridinoline excretion were
      within reference ranges. Treatment with prednisolone induced a prompt improvement
      with normalization of serum concentrations of ionized calcium and 1,25-(OH)2D3.
      Serum intact osteocalcin concentration was markedly suppressed and urinary
      deoxypyridinoline excretion increased. It is possible suppressed bone resorption
      may be associated with overproduction of 1,25-(OH)2D3.

PMID- 12521212
TI  - Philadelphia chromosome-positive chronic myeloid leukemia expressing p190(BCR
      ABL).
AB  - We describe a case of Philadelphia chromosome-positive chronic myeloid leukemia
      (Ph-positive CML) expressing p190(BCR-ABL). Reverse transcription-polymerase
      chain reaction (RT-PCR) analysis of bone marrow cells showed a 472-bp band using
      primers specific for the p190(BCR-ABL) but not p210(BCR-ABL) transcript.
      Sequencing analysis revealed that the PCR product was derived from the fusion
      between BCR exon e1 and ABL exon a2 (e1a2). CML expressing p190(BCR-ABL) is
      relatively rare. In a review of the literature, it may be grouped into 2
      categories; approximately half of the patients exhibited prominent monocytosis
      and intermediate hematological phenotype between CML and chronic myelomonocytic
      leukemia, and the remaining patients showed no monocytosis.

PMID- 12521211
TI  - Humidifier lung: possible contribution of endotoxin-induced lung injury.
AB  - A 56-year-old man was admitted with cough, fever, myalgia, and arthralgia. Chest
      computed tomography demonstrated bilateral diffuse ground-glass opacities
      predominantly in the upper lungs. Subpleural non-segmental consolidation was
      observed in the late phase. Hypersensitivity pneumonitis was suspected, and an
      environmental provocation test with the incidental use of a home ultrasonic
      humidifier was positive. Unlike typical hypersensitivity pneumonitis, serum KL-6
      levels were normal. Although several microorganisms were isolated from the
      humidifier water, there was no evidence for immune sensitization. We detected
      high amounts of endotoxin in the humidifier water, which may have contributed to
      the lung injury of this patient.

PMID- 12521213
TI  - Hepatitis A virus infection associated with hemophagocytic syndrome: report of
      two cases.
AB  - Virus-associated hemophagocytic syndrome (VAHS) is reported to be a rare
      complication in hepatitis A virus infections. We encountered two patients with
      hepatitis A virus-associated hemophagocytic syndrome (HAV-AHS). Although
      hemophagocytosis associated with other types of virus infections is fatal, the
      present patients with HAV-AHS recovered well without any treatment.
      Thrombocytopenia is an initial important finding of VAHS which is not rare in
      patients with acute hepatitis A. If bone marrow aspiration is performed more
      frequently, more HAV-AHS will be diagnosed. Further investigations are necessary
      to clarify the clinical features of HAV-AHS in more patients.

PMID- 12521214
TI  - Early diagnosis of vertebral dissecting aneurysm: a magnetic resonance
      angiography study.
AB  - We report a patient with dissecting aneurysm who presented with a sudden severe
      headache without any neurological symptoms. Although brain computed tomography
      (CT) scan and MRI were negative, magnetic resonance angiography (MRA) showed a
      pseudocavity in a segment of the left vertebral artery. In addition, the
      dissecting wall of the left vertebral artery was clearly visualized in the
      original images of MRA. Our findings indicate that brain CT, MRI or cerebral
      angiography alone are sometimes inadequate for the diagnosis of vertebral
      dissecting aneurysm, and that MRA and its original images are necessary to
      establish the correct diagnosis.

PMID- 12521215
TI  - Diurnal fluctuation of edema synchronized with plasma VEGF concentration in a
      patient with POEMS syndrome.
AB  - A case of POEMS syndrome in a 49-year-old Japanese woman is reported. The patient
      exhibited prominent edema in her legs at night, but her edema usually improved by
      the following morning. The plasma concentrations of VEGF in the patient showed
      diurnal fluctuations; plasma VEGF levels peaked at night and decreased in the
      daytime. Immunocytochemical study demonstrated the expression of VEGF in IgA- and
      lambda-positive plasma cells in bone marrow. The results indicate that VEGF was
      produced at least by plasma cells and that VEGF production was regulated by
      circadian rhythm in synchronization with the development of edema.

PMID- 12521216
TI  - Anti-Ku antibody-positive scleroderma-dermatomyositis overlap syndrome developing
      Graves' disease and immune thrombocytopenic purpura.
AB  - Graves' disease (GD) has been reported to be frequently complicated with other
      autoimmune diseases. However, it is rarely complicated with scleroderma
      polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who
      developed GD and immune thrombocytopenic purpura during follow-up observation of
      scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after
      high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The
      present case is the first report of a combination of scleroderma,
      dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku
      antibody-positive and had relatively low natural killer T cell counts, both of
      which might contribute to the complication of multiple autoimmune diseases.

PMID- 12521217
TI  - Propylthiouracil-induced lupus-like syndrome developing in a Graves' patient with
      a sibling with systemic lupus erythematosus.
AB  - A 13-year-old girl with Graves' disease, whose younger sister had systemic lupus
      erythematosus, developed polyarthralgia, fever, neutropenia,
      hypergammaglobulinemia, and microscopic hematuria after treatment with
      propylthiouracil (PTU) for 2 years. Myeloperoxidase-anti-neutrophil cytoplasmic
      antibodies were strongly positive. Anti-single- and anti-double-stranded DNA
      antibodies were positive, whereas LE cells and anti-Sm antibodies were negative.
      PTU was discontinued and all symptoms subsided gradually. Two years later, the
      microscopic hematuria had disappeared completely. Both patients had the identical
      HLA-DR alleles (HLA-DR9). These present two cases in siblings suggest that both
      sisters had lupus diathesis, and that the elder sister developed a PTU-induced
      lupus-like syndrome.

PMID- 12521218
TI  - Successful treatment with paclitaxel of advanced AIDS-associated Kaposi's
      sarcoma.
AB  - Kaposi's sarcoma (KS) is the most prevalent AIDS-associated tumor. We report a 44
      year-old Japanese man with advanced AIDS-associated KS, which was spread over
      bilateral pulmonary parenchyma. He was initially treated with combination
      chemotherapy with a partial response. Upon the recurrence of his KS two months
      after the completion of the combination chemotherapy, the patient received
      paclitaxel, which brought about a complete response. Highly active antiretrovial
      therapy (HAART) was initiated three months before the combination chemotherapy,
      and the CD4+ T-cell count had risen before starting paclitaxel. His dinical
      course suggests that paclitaxel was highly effective for KS disease control as
      previously reported, and that immune restoration with HAART is crucial in the
      treatment of KS.

PMID- 12521219
TI  - Hydroxyl radical generation by the combination of iron and ascorbic acid is
      greatly attenuated but still significant in human gastric juice.

PMID- 12521220
TI  - An Asian variant of intravascular lymphoma diagnosed through splenectomy.

PMID- 12521221
TI  - Procerus sign in corticobasal degeneration.

PMID- 12521222
TI  - Sickle cell disease--pathophysiology, clinical and diagnostic implications.
AB  - We review the current knowledge of the pathophysiology of sickle cell disease
      (SCD), the clinical complications and the state of the art in SCD diagnostics.
      Today, a flexible laboratory concept allows the fast and economic clarification
      of the patients' sickle cell hemoglobin (HbS) status, e.g. additional compound
      heterozygosities. In contrast to a well-investigated pathophysiology of the
      disease, factors influencing the severity of symptoms as well as some laboratory
      findings in SCD still lack a final explanation. In this review, we focus on red
      cell lysis resistance as an additional diagnostic tool in SCD. There is a need
      for further studies regarding lysis resistance in blood samples from patients
      with HbS.

PMID- 12521223
TI  - Family studies: their role in the evaluation of genetic cardiovascular risk
      factors.
AB  - Early epidemiological studies showed that genetic factors contribute to the risk
      of cardiovascular disease. Genetic epidemiological studies based upon families
      can be used to investigate familial trait aggregation, to localize genes
      implicated in cardiovascular diseases in the human genome, and to establish the
      role of environmental factors. Family studies can be also used to identify the
      physiological role of candidate genes for cardiovascular diseases, and to
      characterize shared environmental risk factors and their impact on the expression
      of genetic predisposition. The present paper reviews the existing family studies
      with special emphasis on those which have studied healthy populations in relation
      to cardiovascular disease such as the Framingham Heart Study, the National Heart,
      Lung, and Blood Institute Family Heart Study, and the STANISLAS cohort.

PMID- 12521224
TI  - Polymorphisms in the lipopolysaccharide-binding protein and
      bactericidal/permeability-increasing protein in patients with myocardial
      infarction.
AB  - Gram-negative bacterial infection, namely Chlamydia pneumoniae has been recently
      discussed as a risk factor for myocardial infarction. The lipopolysaccharide
      binding protein (LBP) and the bactericidal/permeability-increasing protein (BPI)
      play a role in the processes leading to recognition and neutralisation of the
      Chlamydia pneumoniae and their endotoxins lipopolysaccharides (LPS). LPS interact
      with plasma LBP, and LBP-LPS complex activates monocytes/macrophages, which can
      influence the atherosclerotic process. BPI is cytotoxic for Gram-negative
      bacteria and BPI-LPS complexes do not activate monocytes. We have analysed the
      polymorphisms in the LBP gene (Gly98-->Cys; Pro436-->Leu) and BPI gene (Lys216-
      >Glu; PstI polymorphism in intron-5; G545-->C) in 313 patients after myocardial
      infarction (MI) and in 302 control individuals. Genotype frequencies in the LBP
      gene and BPI gene did not differ between MI patients and control individuals. Our
      findings suggest that LBP and BPI polymorphisms do not influence the risk of MI.

PMID- 12521225
TI  - Effect of S-(1,2-dicarboxyethyl) glutathione and S-(1,2-dicarboxyethyl) cysteine
      on the stimulus-induced superoxide generation and tyrosyl phosphorylation of
      proteins in human neutrophils.
AB  - We investigated the effects of S-(1,2-dicarboxyethyl) glutathione (DCEG) and S
      (1,2-dicarboxyethyl) cysteine (DCEC) on the stimulus-induced superoxide
      generation and tyrosyl phosphorylation of proteins in human neutrophils. When the
      cells were preincubated with DCEG, the superoxide generation induced by N-formyl
      methionyl-leucyl-phenylalanine (fMLP) was enhanced in concentration-dependent
      manner but DCEC showed no effect. The influence of DCEG and DCEC on phorbol 12
      myristate 13-acetate-induced superoxide generation showed no effect. On the other
      hand, the superoxide generation induced by arachidonic acid was markedly
      suppressed by DCEG and DCEC in concentration-dependent manner. The suppression of
      DCEG was more effective than that of DCEC. The superoxide generation induced by
      fMLP in the DCEG-treated cells was suppressed by genistein. DCEG enhanced tyrosyl
      phosphorylation of 80.0 kDa, 60.0 kDa, and 45.0 kDa proteins in human
      neutrophils. The tyrosyl phosphorylation of 80.0 kDa, 60.0 kDa, and 45.0 kDa
      proteins was suppressed by genistein. The enhancement of tyrosyl phosphorylation
      of these proteins in the DCEG-treated cells was parallel to the enhancement of
      the fMLP-induced superoxide generation.

PMID- 12521227
TI  - Frequencies of Q188R and N314D mutations and IVS5-24g>A intron variation in the
      galactose-1-phosphate uridyl transferase (GALT) gene in the Slovenian population.
AB  - Numerous mutations in the galactose-1-phosphate uridyl transferase (GALT) gene
      have been found to impair GALT activity to different extent, causing
      galactosemia. This disorder exhibits considerable allelic heterogeneity in
      different populations and ethnic groups. The Q188R mutation accounts for 60-70%
      of classical galactosemia alleles in the Caucasian population. Individuals
      homoallelic for Q188R have a severe phenotype with complete loss of enzyme
      activity. Another form of GALT deficiency is Duarte galactosemia with N314D
      mutation associated alleles (Duarte-2). Although heterozygotes for classical
      galactosemia are asymptomatic at birth and Duarte galactosemia appears to be
      quite benign, there are some indications that these disorders can increase the
      risk of developing certain diseases later in life. The aim of our study was to
      analyze a healthy Slovenian population for the frequencies of Q188R and N314D
      mutations, and for the Duarte-2 indicative intronic variation IVS5-24G>A. DNA
      samples from 174 healthy subjects were analyzed for all three mutations by
      polymerase chain reaction and digestion with restriction enzymes. Allele
      frequencies for Q188R and N314D mutations and IVS5-24G>A intron variation were
      found to be 0.29%, 8.0% and 5.7%, respectively. These results correlate well with
      those reported for most other healthy Caucasian populations.

PMID- 12521226
TI  - Hyperhomocysteinemia is related to a decreased blood level of vitamin B12 in the
      second and third trimester of normal pregnancy.
AB  - Hyperhomocysteinemia has been associated with several pregnancy complications. We
      have investigated the variation of plasma total homocysteine (tHcys) during the 2
      last trimesters of normal pregnancy and related it to blood vitamin B12 and
      folate and to the excretion of the degraded intrinsic factor receptor (IFCR) in
      urine, in a follow-up study of 15 cases. A significant rise in tHcys was observed
      between the beginning of the second trimester and the third trimester with
      respective values (median) 6.1, 5.8 and 6.7 micromol/l (p = 0.038). The
      tHcys/albumin ratio also increased significantly, while no correlation was found
      between albumin and folate blood concentration. In contrast, a significant
      decrease in vitamin B12 was observed (279, 225 and 199 pmol/l, between the 4th
      and 6th, and the 6th and 9th month, respectively (p = 0.017-0.002)). A
      significant negative correlation was found between tHcys between the 4th and 9th
      month of pregnancy and the ratio of vitamin B12 between the 4th and 9th month of
      pregnancy (r = 0.55, p = 0.037). The urine excretion of IFCR was increased and
      was not related to vitamin B12 and tHcys. In conclusion, we have observed a rise
      in tHcys between the beginning of the second trimester and the third trimester of
      pregnancy which was related to the decreased blood level of vitamin B12.
      Subclinical deficiency of vitamin B12 should be further investigated in pregnant
      women who remain on inadequate diet.

PMID- 12521228
TI  - Umbilical cord and maternal blood leptin concentrations in intrauterine growth
      retardation.
AB  - Leptin, the ob gene product, plays an important role in the regulation of body
      fat mass and weight. In previous studies, it was demonstrated that leptin is
      detectable in human fetal cord blood as early as at 18 weeks of gestation and
      that serum leptin concentrations are significantly reduced in small gestational
      age newborns. In the present study, we investigated whether umbilical and
      maternal serum leptin concentrations correlate with intrauterine growth
      retardation (IUGR). In addition, we aimed to determine the relationships between
      leptin concentration in the maternal and cord blood. We studied 40 newborn
      infants (21 female and 19 male; gestational age, 38-42 weeks) and their mothers.
      Of the infants studied, 10 had IUGR. Serum leptin concentrations were measured by
      radioimmunoassay. All newborns had detectable leptin concentrations. Leptin
      concentrations were significantly lower in newborns with IUGR and in their
      mothers (n = 10; 3.53 +/- 1.42 ng/ml, 6.75 +/- 1.47 ng/ml, respectively) than in
      infants experiencing normal growth and their mothers (n = 30; 5.58 +/- 2.98
      ng/ml, 9.85 +/- 6.50 ng/ml, respectively) (p < 0.01 for newborns, p < 0.05 for
      mothers). There was no significant correlation between umbilical leptin
      concentration and maternal leptin concentration (r = 0.229; p = 0.155) in all
      study groups but, significantly, a correlation was observed in the group with
      IUGR (r = 0.736; p = 0.015). There were no significant correlations between both
      umbilical and maternal leptin concentrations and parity, delivery type and
      gestational age. There was a correlation between umbilical leptin concentration
      and birth weight of newborns (r = 0.383; p = 0.015) but no correlation with body
      mass index (BMI) of the newborns (r = 0.034; p = 0.834). Maternal leptin
      concentrations correlated with maternal weight and BMI (r=0.606; p=0.000,
      r=0.535; p=0.000, respectively). There was no correlation between maternal leptin
      concentrations and birth weight of the newborns (r=0.179; p=0.269) and with BMI
      of the newborns (r = 0.146; p = 0.367). There was no gender difference in leptin
      concentrations in the newborns (n=21; 5.50 +/- 3.37 ng/ml, for females; n = 19;
      4.58 +/- 1.98 ng/ml for males) (p = 0.296). In summary, we have shown that IUGR
      is associated with a decreased leptin concentration in newborns and their
      mothers. The association between umbilical serum leptin and birth weight in this
      and other studies suggests a pivotal role of fetal leptin in regulating fetal
      growth and development.

PMID- 12521229
TI  - Blood concentrations of selenium, zinc, iron, copper and calcium in patients with
      hepatocellular carcinoma.
AB  - We used an atomic absorption spectrophotometric method to determine the
      concentration of selenium, zinc, iron, copper and calcium in the whole blood of
      patients with hepatocellular carcinoma. The results demonstrate that these
      patients have a lower concentration of selenium (0.18 +/- 0.02 microg/ml vs. 0.28
      +/- 0.06 microg/ml) and zinc (11.2 +/- 2.75 microg/ml vs. 18.2 +/- 7.33
      microg/ml) than healthy controls (p < 0.05). On the other hand, the
      hepatocellular carcinoma patients have higher mean concentrations of iron
      (651.9+/-66.2 microg/ml vs.473.0 +/- 88.0 microg/ml; p < 0.05), copper (1.43 +/-
      0.33 microg/ml vs. 0.95 +/- 0.19 microg/ml; p < 0.05) and calcium (75.0 +/- 13.1
      microg/ml vs. 39.9 +/- 12.3 microg/ml; p < 0.01) than healthy controls. Thus,
      hepatocellular carcinoma seems to be associated with the changes in the whole
      blood concentrations of selenium, zinc, iron, copper and calcium.

PMID- 12521230
TI  - TaqMan systems for genotyping of disease-related polymorphisms present in the
      gene encoding apolipoprotein E.
AB  - Polymorphisms of the gene encoding apolipoprotein E have been implicated in the
      pathogenesis of peripheral and coronary artery disease and neurodegenerative
      disorders such as sporadic and late-onset familial forms of Alzheimer's disease.
      We have developed TaqMan assay systems for the single nucleotide polymorphisms 
      219G/T, located in the promoter of the apolipoprotein E gene, 113G/C, present in
      the transcriptional enhancer element of intron 1, 334T/C, determining Cys or Arg
      as amino acid residue 112 of mature apolipoprotein E, and 472C/T, determining Arg
      or Cys as residue 158. The accuracy of genotype determination with the TaqMan
      systems was demonstrated by analyses with restriction endonucleases. We
      determined the genotypes of the apolipoprotein E polymorphisms in 2349 study
      subjects. The genotypes were distributed as: -219GG = 27.3%, -219GT = 49.1%, and 
      219TT = 23.6% (p = 0.435); 113GG = 41.3%, 113GC = 45.2%, and 113CC = 13.5% (p =
      0.343); 334TT = 73.4%, 334TC = 24.7%, and 334CC = 1.9% (p = 0.539); 472CC =
      86.3%, 472CT=12.8%, and 472TT= 0.9% ( p = 0.004) (Hardy-Weinberg equilibrium
      estimates are given in parentheses). The allele combinations which define the
      three major isoforms of apolipoprotein E, namely apoE2, apoE3, and apoE4, had the
      following allele frequencies: 334T/472T (epsilon2; 112Cys/158Cys) = 7.3%,
      334T/472C (epsilon3; 112Cys/158Arg) = 78.4%, and 334C/472C (epsilon4;
      112Arg/158Arg) = 14.2%, respectively. ApoE genotypes were distributed as:
      epsilon2epsilon2 = 0.9%, epsilon2epsilon3 = 11.2%, epsilon2epsilon4 = 1.6%,
      epsilon3epsilon3 = 61.3%, epsilon3epsilon4 = 23.1%, and epsilon4epsilon4 = 1.9%
      (p = 0.014). The TaqMan assays allow for fast and sensitive genotyping and are
      especially suitable for studies including large numbers of participants.

PMID- 12521231
TI  - Antioxidant status in thyroid dysfunction.
AB  - Our study was designed to test and compare the levels of enzymatic antioxidants
      (ARS), endogenous peroxides (POX), non-enzymatic antioxidants (Antiox-cap) and
      anti-oxidized low-density lipoprotein (LDL) antibody titers (oLAb) in
      hyperthyroid and hypothyroid patients. We measured POX, ARS, Antiox-cap and oLAb
      in the plasma from 68 patients (34 patients with hyperthyroidism, thyroid
      stimulating hormone (TSH) <0.04; and 34 patients with hypothyroidism, TSH >4.0)
      and 34 healthy euthyroid controls. POX were highest in hyperthyroid patients, but
      differences between hyperthyroid and hypothyroid patients and controls were not
      significant. ARS were significantly higher in patients compared to controls.
      Antiox-cap were significantly lower in patients compared to controls. oLAb were
      significantly higher in hypothyroid patients compared to controls and
      hyperthyroid patients. Our study shows that both hyperthyroidism and
      hypothyroidism are associated with enhanced oxidative stress involving enzymatic
      and non-enzymatic antioxidants. Higher POX in hyperthyroid patients might reflect
      the hypermetabolic state of these patients. oLAb, indicating progression of
      atherosclerosis, were highest in hypothyroid patients.

PMID- 12521232
TI  - Diagnostic efficiency of cystatin C and serum creatinine as markers of reduced
      glomerular filtration rate in the elderly.
AB  - This is a secondary analysis of data from a cross-sectional study to evaluate the
      diagnostic efficiency of cystatin C as a marker of the glomerular filtration rate
      in the elderly. Thirty patients (15 male, 15 female, mean age 75.4 +/- 7.1 years)
      attending a geriatric ward were enrolled. Exclusion criteria were previously
      diagnosed renal disease, dementia and heart failure (NYHA III or IV). Cystatin C
      in serum was determined by a particle-enhanced turbidimetric assay. Inulin
      clearance was assessed using a single-shot method. Also, Cockcroft-Gault formula
      was calculated. Twelve patients had a reduced glomerular filtration rate (<70
      ml/min/ 1.73 m2). The mean values were 88.4 micromol/l (+/- 27.7) for serum
      creatinine, 1.57 mg/l (+/- 0.34) for cystatin C and 88.7 ml/min/1.73 m2 (+/-
      34.6) for inulin clearance. Maximum efficiency was 0.73 for serum creatinine (cut
      off limit 82 micromol/l), 0.67 for cystatin C (cut-off limit 1.63 mg/l) and 0.8
      for Cockcroft and Gault estimation (cut-off limit 54 ml/min/1.73 m2). A receiver
      operating characteristics (ROC) analysis did not show any differences between the
      various methods. Therefore, cystatin C in serum may not improve the diagnostic
      efficiency in detecting a reduced glomerular filtration rate in the elderly.
      Furthermore, normal ranges for serum creatinine in the elderly might need to be
      adjusted.

PMID- 12521233
TI  - Comparing different methods for homocysteine determination.
AB  - Slightly elevated values of homocysteine are commonly associated with
      thromboembolic diseases, while high values can be found in patients with
      congenital metabolic defects or nutritional problems. The clinical use of
      homocysteine as an independent marker of cardiovascular disease was limited in
      the past by technical problems with its measurement, the instrumentation (HPLC,
      radioenzymatic assays, gas chromatography-mass spectrometry, etc.) and the
      necessary skills required. Commercially available immunoassays now permit a
      simpler and more rapid measurement of homocysteine, that is more suitable for
      routine clinical laboratories; in this paper we analyze the results obtained by
      using three fully automated methods for homocysteine determination (Abbott IMx
      immunoassay, Abbott AxSYM immunoassay and Immulite 2000 homocysteine immunoassay)
      and their correlation with the widely used HPLC method. The results clearly
      indicate that all three automated immunochemical methods correlate well with the
      HPLC method (slope 0.97-1.03; intercept 0.95-1.91 with a recovery above 95% for
      all three methods).

PMID- 12521234
TI  - Classification of renal proteinuria: a simple algorithm.
AB  - Total protein, albumin, alpha1-microglobulin, and immunoglobulin G (IgG) were
      analyzed in 1,622 urine samples without Bence-Jones proteinuria or gross
      hematuria. There was correlation with the histological picture obtained on renal
      biopsy in 61 patients. We established 24-h reference intervals for alpha1
      microglobulin and IgG on 659 urine samples with total protein and albumin
      excretion rates below 100 mg/24 h and 30 mg/24 h, respectively, and creatinine
      clearance above 80 ml/min. The central 95% reference interval was found to be
      between 4 and 17 mg/24 h for alpha1-microglobulin and between 3 and 8.5 mg/24 h
      for IgG. In 80 urine samples with albumin excretion rate above 30 mg/24 h and
      alpha1-microglobulin and IgG within their reference intervals, we analyzed the
      95% central interval of the distribution of the IgG/albumin ratios, and it was
      found to be within 0.01 and 0.20 (0.90 confidence interval: 0.17-0.24).
      Proteinuria was considered to be of the selective glomerular type if the albumin
      excretion rate was abnormal and the IgG/albumin ratio was under 0.20, even when
      the IgG excretion was within a pathological range. For the classification of
      proteinuria as predominantly tubular, we estimated the alpha1
      microglobulin/albumin ratio in 173 urine samples with normal excretion rates of
      albumin and IgG and pathological excretion of alpha1-microglobulin. The
      discriminating value of 0.91 (0.90 confidence interval: 0.78-1.08) was accepted
      in order to define proteinuria of a tubular origin in the presence of a
      pathological albumin excretion rate. The association between albumin and IgG
      excretion rates and tubular reabsorption of the alpha1-microglobulin normally
      filtered by the glomerulus was studied in 33 urine samples from patients with no
      histologically significant tubulo-interstitial or vascular disease and a serum
      creatinine concentration below 141 pmol/l. The optimal curve-fitting function
      between albumin plus IgG and alpha1-microglobulin excretion rates was of the
      quadratic type (r = 0.927). Mixed proteinuria was considered when both, albumin
      and alpha1-microglobulin excretion rates were pathological and could not be
      included in the previously described groups.

PMID- 12521235
TI  - Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH),
      estradiol (E2), prolactin, progesterone, sex hormone-binding globulin (SHBG),
      dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin in neonates,
      children and young adults.
AB  - The aim of this study was to establish reference ranges for children (neonates to
      young adults), for serum lutropin (LH), follitropin (FSH), estradiol (E2),
      progesterone, prolactin, sex hormone-binding globulin (SHBG),
      dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin, using the
      nonisotopic, automated chemiluminescence immunoassay system, Immulite (DPC).
      Serum samples from 762 children (369 female; age 1 day to 19 years) were
      examined. Of these, 381 were classified as pubertal. Due to non-normal
      distribution, the 2.5th, 50th and 97.5th percentiles (central 95% interval) were
      calculated for each group. Statistical differences between the reference ranges
      were analyzed with respect to age, sex and the stage of sexual maturation. The
      median concentrations of E2, prolactin, progesterone, DHEAS, cortisol and
      ferritin were higher during the first 2 weeks post-partum than thereafter. The
      largest difference was seen with prolactin, which showed up to 27-fold higher
      values during this period. In contrast, before the onset of puberty, hardly any
      sex difference was observed and all analyte concentrations remained relatively
      constant, apart from SHBG which increased steadily after the neonatal period. The
      increase of gonadal activity in females with the onset of sexual maturation
      included an increase in LH and FSH, which was accompanied by a strong increase in
      E2, progesterone and prolactin. Cortisol increased to a lesser extent during
      puberty. In males, the increase in the median concentrations of the hormones was
      smaller, except for DHEAS. The concentration of ferritin was high in the neonatal
      period but did not change during sexual maturation. Our findings agree with
      earlier studies. The calculated reference intervals can be used to assess the
      development of children, particularly for measurements performed by the Immulite
      and Immulite 2000 chemiluminescence assay systems.

PMID- 12521236
TI  - Validation of a kinetic model for the reactions in RIA.
AB  - The goal of this work was to check the validity of a model previously described
      for the study of kinetics of the processes taking place during the immuno
      analytical measurement of insulin. The antibody was immobilized on the suface
      wall of the reaction tube. Tracer and insulin concentration, temperature,
      viscosity and ionic strength in the reaction medium were taken as independent
      variables. Biexponential kinetics depending on the concentration was observed.
      The results of the viscosity study show a clear negative influence of this
      parameter on the direct reaction velocity. Ionic strength had a slight effect,
      which suggests that the observed variation due to the addition of glycerol is not
      induced by the influence of the dielectric constant of the solution used. The
      effect of the temperature shows activation parameters similar to water flow
      viscosity energy, which suggests a diffusion control for the reaction. The
      proposed model correctly interprets the influence of the studied variables.

PMID- 12521237
TI  - Automated counting of cells in cerebrospinal fluid using the CellDyn-4000
      haematology analyser.
AB  - Counting of cells in cerebrospinal fluid is currently performed manually. Because
      of the inherent analytical and economical disadvantages, we attempted to
      introduce a fully automated method. Therefore, we validated the Abbott CellDyn
      4000 haematology analyser for counting cells in cerebrospinal fluid. The analyser
      was used in its standard configuration with the simple precaution of a preceding
      blank sample. As for leukocyte counting the analyser yielded high precision (CV
      approximately 5% above the upper reference limit), good linearity, low limit of
      detection (2/microl) and excellent correlation (r > 0.99) with the counting
      chamber method. The differential leukocyte count was equally accurate and
      precise, even in the low concentration range. Performance of the erythrocyte
      count was impaired by its high limit of detection (6/nl) and it appeared
      satisfactory only for detecting blood admixture due to traumatic puncture. The
      specificity of the analyser is excellent, since it correctly classified non
      viable leukocytes and excluded yeast cells from the leukocyte count in a patient
      with cryptococcal meningitis. We conclude that the CellDyn-4000 is well suited
      for quickly and reliably counting leukocytes in cerebrospinal fluid. Developing
      some software modifications might make the analyser useful also for performing
      erythrocyte counting in cerebrospinal fluid.

PMID- 12521238
TI  - Urine trans,trans-muconic acid levels in residents of a business area of Bangkok,
      Thailand.

PMID- 12521240
TI  - Things visible and invisible: the Leather Archives and Museum.
AB  - This paper explores the reasons underlying the relative absence of research on
      the leather/levi community in gay and lesbian studies and summarizes the history
      and special collections of Chicago's Leather Archives and Museum.

PMID- 12521239
TI  - Hemoglobin electrophoresis in Thai non-anemic pregnant subjects, a need for
      additional screening for hemoglobin E.

PMID- 12521241
TI  - The institutional climate for lesbian, gay and bisexual education faculty: what
      is the pivotal frame of reference?
AB  - This article presents data gathered from a national sample (n = 104) of lesbian,
      gay, and bisexual education faculty members and researchers. Here, the author
      examines three general dimensions through which these respondents judge their
      institutional climate--characterized as gay affirming, gay tolerant, gay neutral,
      gay intolerant, or gay hostile--and four unique factors that distinguish their
      assessment. Four questions are addressed: (1) How do sexual minority faculty in
      schools, colleges, and departments of education characterize their institutional
      climate? (2) What institutional dimension is most salient in these faculty
      members' assessment of this climate? (3) What are the factors that differentiate
      sexual minority faculty members' perceptions in this study? (4) Which of these
      factors, if any, significantly contribute to their assessment of institutional
      climate? Using multivariate analyses, the author identifies one pivotal frame of
      reference that accounts for most of the variance in respondents' differing
      assessments of their institutional climate and explores differences between
      lesbian and gay male respondents as well as those working in public and private,
      independent institutions. Implications for those seeking to reduce institutional
      heterosexism and homophobia are discussed.

PMID- 12521242
TI  - Prejudice, internalization, and the accessibility of personal standards for
      responding to gay men.
AB  - Heterosexual participants who were very low, moderately low, moderately high and
      very high in prejudice toward gay men reported their personal standards for
      responding to gay men (i.e., how they believed they should feel or think in an
      imagined scenario involving a gay man) via computer. As expected, the standards
      of very low-prejudice individuals were the least prejudiced, the most
      internalized (i.e., most important and central to the self), and the most
      accessible (i.e., reported most quickly). Regression analyses revealed the
      predicted relation between accessibility and internalization, such that the more
      internalized the standard the greater its accessibility. A significant quadratic
      trend for prejudice revealed that accessibility decreases with increasing
      prejudice, except that at very high levels of prejudice accessibility begins to
      increase. Implications for prejudice reduction for both low- and high-prejudice
      individuals are discussed.

PMID- 12521243
TI  - Attitudes toward gay, lesbian, and bisexual persons among heterosexual liberal
      arts college students.
AB  - This research focuses on attitudes toward homosexuals and homosexuality among 692
      heterosexual students at six liberal arts colleges. Attitudes, assessed in a
      variety of ways, are examined in relation to students' Greek affiliation, sex
      role attitudes, religion and religiosity, and contact with and knowledge of gays,
      lesbians, and bisexuals. Results suggest that attributes predicting acceptance of
      gay, lesbian, and bisexual persons are female sex, liberal sex-role attitudes,
      lower religiosity as measured both by beliefs and by attendance, membership in
      more liberal Protestant denominations, attendance at colleges that do not have
      Greek letter social organizations, and having positive contacts with gay,
      lesbian, and/or bisexual persons.

PMID- 12521244
TI  - Gender differences and attitudes towards homosexuality.
AB  - The aim of this research is two-fold. First, it examined individuals' attitudes
      towards homosexuals in Singapore. Second, it also investigated whether gender
      differences in attitudes towards homosexuals exist. Respondents comprised 365
      students and data were collected through the use of questionnaires. Results
      generally suggested that respondents harboured negative attitudes towards
      homosexuals. The prevalence of such ambivalent attitudes seemed to suggest that
      respondents were still generally quite conservative in their attitudes towards
      gender roles and homosexuality. Our findings also revealed that, generally, women
      reported that they were more comfortable in working closely with male homosexuals
      while the reverse was true for men. Implications of our findings were discussed.

PMID- 12521245
TI  - Suspected adverse reactions, 2001.

PMID- 12521246
TI  - Sea lice infestations on farmed Atlantic salmon in Scotland and the use of
      ectoparasitic treatments.
AB  - A recently compiled national database on sea lice infestations on farmed Atlantic
      salmon, contains detailed records for the period 1996 to 2000 from over 30
      commercial sites on the west coast of Scotland. The data indicate that the two
      prevalent species of lice, Lepeophtheirus salmonis and Caligus elongatus, have
      different trends in abundance and distinctive seasonal patterns of infestation on
      farmed salmon. For the economically important species L salmonis, its abundance
      on fish varies with the time of the production cycle, the time of year and the
      particular year. Weekly fluctuations in sea lice counts indicate that treatment
      can be very effective in controlling infestations but that the counts recover
      rapidly and regular treatments are necessary to ensure control. A comparison of
      sites using medium or large numbers of treatments suggests that they do not
      reduce sea lice infestations to the same levels. There is also evidence that
      sites using treatments based on different chemical constituents had significantly
      different levels of infestation.

PMID- 12521247
TI  - M gene evolution of canine coronavirus in naturally infected dogs.
AB  - Two stray pups (A and B), three and five months old, respectively, both naturally
      infected with canine coronavirus (CCoV), were studied for 180 days. The virus was
      detected intermittently in the pups' faeces by PCR for periods of 156 and 146
      days, respectively. Sequence analysis of a fragment of the gene encoding the M
      protein revealed that the viruses detected at the onset of the infection were
      very similar to typical strains of CCoV, whereas from 42 days after infection in
      pup A and 40 days after infection in pup B the viruses had nucleotide and amino
      acid mutations resembling sequences in feline coronavirus.

PMID- 12521248
TI  - New method for objectively assessing lameness in broiler chickens.
AB  - A new method for assessing the severity of lameness in broiler chickens is
      described. The length of time that birds remained standing in shallow water was
      measured and the results were compared with the results of conventional gait
      scoring. There was a highly significant (P < 0.001) relationship between the
      birds' gait scores and their latency to lie down. Over 750 broilers aged between
      32 and 45 days of age were tested in commercial houses and whereas nearly all the
      sound birds were able to stand for at least 15 minutes, the majority of lame
      birds lay down within five minutes.

PMID- 12521249
TI  - Detection of Lawsonia intracellularis in wild pigs in the Czech Republic.

PMID- 12521250
TI  - Mastitis caused by Yersinia pseudotuberculosis in a cow.

PMID- 12521251
TI  - T3-T4 disc herniation in a German shepherd dog.

PMID- 12521252
TI  - Carcinoid in the lung of a hooded seal (Cystophora cristata).

PMID- 12521253
TI  - Efficacy of selamectin in the treatment of canine cheyletiellosis.

PMID- 12521254
TI  - Supply of medicines and herd health planning.

PMID- 12521256
TI  - Quality assurance of milk somatic cell count results.

PMID- 12521255
TI  - Quality assurance of milk somatic cell count results.

PMID- 12521258
TI  - Retraining course in small animal practice.

PMID- 12521259
TI  - Ovarian teratoma in a camel (Camelus dromedarius).

PMID- 12521260
TI  - The ecology of fish parasites with particular reference to helminth parasites and
      their salmonid fish hosts in Welsh rivers: a review of some of the central
      questions.
AB  - Ecological studies carried out in Welsh rivers on the feeding behaviour of
      salmonid fish, their helminth parasites and intermediate hosts in the early 1950s
      and in 1998 have been used as a basis to review the literature dealing with the
      following questions. First, how are the helminth populations dispersed in space
      time? Second, to what extent are the distributional patterns and the life history
      strategies of the parasites influenced by physicochemical factors? Third, to what
      extent are populations of helmith parasites in salmonid fish influenced by host
      characteristics including the genome, sex, age, size, social position and Feeding
      behaviour? Fourth, are the populations of parasites regulated in a density
      dependent manner? Fifth, do the parasites influence the survival and wellbeing of
      their salmonid hosts and the evolution of sex? Sixth, to what extent is the
      parasite community influenced by environmental changes including those of an
      anthropogenic nature and can the parasites be used as bioindicators of pollution?
      As with most parasites the helminth species found were highly overdispersed thus
      making it necessary to undertake a log10 (1 + x) conversion for statistical
      analyses. Statistical analyses confirm that the genome, age and sex of salmonid
      fish hosts, the station and seasonal change in radiation levels were significant
      factors in predicting the number of parasites. The evidence given supports the
      hypothesis that the feeding behaviour and habitat selection by the host fish,
      their position in the social hierarchy and the overdispersed nature of the
      transmission sites are the key factors in causing differences in the parasitic
      fauna related to host species, age, size and sex. Differences in the helminth
      parasite community related to station can be explained on the basis of
      differences in water types, sediments and chemistry. Although the evidence
      presented is in accord with the consensus view that temperature is correlated
      with seasonal changes in the abundance of many species of helminth parasites, it
      is argued that it may not be the direct causative mechanism. It is postulated
      that the life history strategy that results in a decline in abundance of the more
      vulnerable adult parasites in the gut of the salmonid hosts during the summer has
      arisen as a result of evolutionary pressures. At this time, the gut environment
      is particularly inhospitable because of the temperature-related enhancement of
      the host's immune mechanism and the increased gut turnover rate. In contrast, the
      larval stages in the immunologically and metabolically more benign intermediate
      host would be under less intensive selective pressures. It is postulated
      therefore that evolutionary pressures have caused the parasites to leave the
      definitive host and concentrate their reproductive efforts in the intermediate
      hosts during the warmer months. Evidence is given in support of the hypothesis
      that the parasite populations are regulated in a density-dependent manner and
      that the regulatory mechanisms may involve the host's immune mechanisms and
      intraspecies competition and interspecies competition of an exploitative or
      interference nature. Quantitative studies using 'K' factor analysis and
      biochemical research to elucidate the nature of the interference mechanisms are
      required to test this hypothesis. The absence of age-related resistance indicates
      an old and stable relationship in which the immunosuppressive and immunoavoidance
      mechanisms of the parasites and hosts, respectively, are in balance. This
      indicates that the introduction of novel parasites or new genetic strains of host
      fish could result in harmful epidemics. Despite causing tissue damage, there was
      no evidence of parasite-induced mortality among the salmonids in the Teifi. This
      finding is in accord with the generally accepted view that most freshwaters are
      not troubled by parasite problems. although parasites are present in abundance.
      In fact, parasite abundance in the salmonid fish in the Teifi was positively
      correlated with the condition factor and the adipose index. Two testable
      hypotheses were advanced to explain these observations. First, the more dominant
      well-conditioned fish in the hierarchy are more likely to acquire parasites
      because they ingest more food items and spend more time in sheltered habitats
      with depositing sediments where transmission mainly occurs. Second, the parasites
      may release factors that stimulate the host's immune and endocrinological systems
      to produce factors that enhance somatic growth and inhibit reproduction of the
      host. This benign relationship is considered to be indicative of long-term
      coevolution. The sex of the fish had a significant influence on the abundance of
      the parasites in total and also on particular species with the bias in all cases
      being in favour of the female fish. This review shows that sex bias in parasitism
      is generally not strong and that male bias in parasitism is not a general rule.
      Taken as a whole, the results fail to support most of the predictions based on
      the Hamilton-Zuk and the immunocompetence hypotheses. Possible hypotheses to
      explain why parasitism tends to be higher in female than in male trout include
      testosterone immunosuppression, corticosteroid-based immune suppression and
      differences between the size and behaviour of the sexes. However, the latter two
      hypotheses have more credence, although testosterone levels are higher in female
      than male trout. Between the early 1950s and 1998 there has been a marked decline
      in the prevalence, abundance and diversity of the helminth parasite communities
      in salmonid fish as well as their intermediate hosts. Possible reasons for these
      declines include heavy metal pollution, increased acidity and habitat degradation
      linked to changes in land use. It is concluded that although helminth parasites
      can provide supplementary information on pollution. the use of biotic indices
      based on the Biological monitoring working party (BMWP) or River invertebrate
      prediction and classification system (RIVPACS) methods are preferable. However,
      as these methods were designed to measure the impact of organic pollution they
      lack the sensitivity for measuring metal pollution. It is advocated therefore
      that new biomonitoring methods should be developed to measure the impact of heavy
      metal pollution using biotic indices based on the sampling of the susceptible
      invertebrate communities inhabiting depositing sediments in the transmission
      sites of helminth parasites.

PMID- 12521261
TI  - Biology of the schistosome genus Trichobilharzia.
AB  - Trichobilharzia is the largest genus within the family Schistosomatidae, covering
      over 40 species of avian parasites. To clarify the existing confusion in the
      systematics of the genus, we recommend combining knowledge of life cycles and
      developmental stages, snail/bird hosts, cytogenetical and molecular data together
      with morphological criteria for the characterization of particular species. The
      high specificity of Trichobilharzia for the intermediate host is a likely
      reflection of the ability to avoid the internal defence of specific snails. The
      spectrum of final hosts (birds) seems to be much wider. The infection of birds-
      trichobilharziasis--may lead to considerable tissue injuries, caused by eggs of
      the parasite or migration of immature/mature worms through the body. Most
      Trichobilharzia (visceral species) migrate through the viscera of the host, but
      nasal species display a neurotropic mode of migration. Due to a low specificity
      of penetrating cercariae, mammals (including humans) can be attacked. This leads
      to cercarial dermatitis, predominantly in sensitized hosts. Experimental
      infections indicate that Trichobilharzia never mature in an incompatible
      (mammalian) host. However, not all cercariae and schistosomula are necessarily
      trapped and eliminated in the skin, and parasites may migrate throughout the
      viscera and the nervous system of mammals. These findings suggest that the
      pathogenicity of Trichobilharzia may have been underestimated in the past and
      health risks associated with trichobilharziasis need to be studied further.

PMID- 12521262
TI  - The consequences of reducing transmission of Plasmodium falciparum in Africa.
AB  - Malaria transmission intensity in Africa varies over several log orders, from
      less than one infected bite per year to more than one thousand. In this review we
      examine the consequences in terms of age pattern, clinical spectrum and overall
      burden of disease and discuss the possible implications for interventions that
      reduce exposure to infected bites. With very low transmission intensity, all age
      groups are susceptible to severe malaria. With increasing transmission
      intensities, older children and adults suffer less severe disease and with high
      transmission rates the majority of severe cases occur in infants under one year
      of age. This pattern reflects the increasingly rapid acquisition of immune
      responses that limit the life-threatening effects of malaria with increasing
      exposure to the parasite. The clinical spectrum of severe malaria varies with
      transmission: with high transmission, severe malarial anaemia dominates and
      cerebral malaria is rare. As one moves towards lower transmission rates, cerebral
      malaria accounts for an increasingly large proportion of cases. Although the
      population risk of severe disease falls with age, the risk of death at an
      individual level may rise with age after an initial fall from very high case
      fatality rates in children aged under 6 months. Of central interest to malaria
      control is how the overall amount of disease in childhood varies with
      transmission. Data from a number of sources suggest that, with low transmission,
      the amount of malarial disease rises with increasing exposure but that this
      saturates relatively early. A key issue is whether the same pattern obtains for
      deaths, both those directly due to malaria and those from all causes. The
      methodological limitations of ecological comparisons between different areas are
      discussed before presenting a review of attempts to use this approach in Africa.
      This suggests that children living in areas of low malarial endemicity have all
      cause mortality rates about half of those of children living in areas of moderate
      to high transmission. Deaths in the first year of life rise linearly with
      increasing exposure to malaria over a wide range of transmission intensities; by
      contrast all-cause mortality in children aged 0-4 years appears to saturate at
      relatively low transmission intensities. These data suggest that interventions
      that reduce exposure to malaria parasites, such as insecticide-treated bed nets
      (ITNs), will have the greatest chance of a sustained effect when used in areas
      where disease burdens are high but the frequency of parasite exposure is low-to
      moderate. In conditions of high transmission, initial reductions in mortality may
      prove difficult to sustain as the reduced level of transmission may still lie on
      the part of the curve where mortality has saturated. However, at all levels of
      transmission the overall balance of benefits, including reduced load on families
      and health services from non-life-threatening malaria, favours the widespread
      introduction of ITNs in endemic areas of Africa.

PMID- 12521263
TI  - Cytokine-mediated host responses during schistosome infections; walking the fine
      line between immunological control and immunopathology.
AB  - Most helminth infections of humans and animals induce similar immune responses,
      which are characterised by the production of Th2-associated cytokines
      (interleukin (IL)-4, IL-5, IL-9, IL-10, IL-13) and antibodies (IgG1--mouse, IgG4-
      man, IgE--both). This type-2-biased immune phenotype generally persists for the
      duration of the infection. Although similar types of immune responses are also
      triggered during allergy, atopy and anaphylaxis, chronic helminth-induced type-2
      associated responses are usually held in check by appropriately regulated control
      mechanisms that limit the destructive potential of prolonged cytokine bias. Among
      numerous reported activities, helminth-induced type-2-associated immune responses
      have been linked to the expulsion of gastrointestinal nematodes and the formation
      of circumoval granulomas during schistosomiasis. However, what happens when this
      highly regulated, and often beneficial, type-2 immune response becomes chronic,
      improperly controlled, or exaggerated during helminth infections? Using
      schistosomiasis as a model disease, we describe the lethal consequences of
      inappropriate immune response induction by reviewing the literature generated
      from experimental animal studies and human epidemiological investigations.
      Development of severe and non-overlapping immunopathological phenotypes will be
      discussed in the context of immune deviation and in the setting of chronic and/or
      hyper-polarised cytokine environments.

PMID- 12521264
TI  - Antimalarial activity of plant metabolites.
AB  - This review covers the structures of compounds with antiplasmodial activity
      isolated from plants and is organized according to plant family. A total of 170
      structures has been reviewed from 186 references found in the literature up to
      December 2000.

PMID- 12521265
TI  - Trends in selenium biochemistry.
AB  - The biochemistry of selenium-containing natural products, including
      selenoproteins, is reviewed up to May 2002. Particular emphasis is placed on the
      assimilation of selenium from inorganic and organic selenium sources for
      selenoprotein synthesis, the catalytic role of selenium in enzymes, and medical
      implications of an unbalanced selenium supply. The review contains 393 references
      on key discoveries and recent progress.

PMID- 12521266
TI  - Indolizidine and quinolizidine alkaloids.
AB  - This review covers the isolation, structure determination, synthesis and
      biological activity of indolizidine and quinolizidine alkaloids from microbial,
      plant and animal sources. Included in the review are slaframine; hydroxylated
      indolizidines and their analogues; alkaloids from ants and amphibians;
      metabolites of the genera Prosopis, Streptomyces and Nuphar and the Lythraceae;
      phenanthroindolizidines and related alkaloids; lupin alkaloids; and alkaloids
      from sponges. tunicates and coccinellid beetles. The literature from July 2000 to
      June 2001 is reviewed, and 172 references are cited.

PMID- 12521267
TI  - Quinoline, quinazoline and acridone alkaloids.
AB  - This review covers the isolation, structure determination, synthesis and
      biological activity of quinoline, quinazoline and acridone alkaloids from plant,
      microbial and animal sources. The literature from July 2000 to June 2001 is
      reviewed, and 119 references are cited.

PMID- 12521268
TI  - Flavoenzymes that catalyse reactions with no net redox change.
AB  - This review covers unusual flavoenzymes that catalyse reactions with no net redox
      change. Some of these enzymes utilise the redox properties of flavin directly in
      catalysis with either two-electron chemistry (N-methylglutamate synthase and 5
      hydroxyvaleryl-CoA dehydratase) or free radical chemistry (chorismate synthase,
      DNA photolyase, (6-4) photolyase and 4-hydroxybutyryl-CoA dehydratase). Whether
      the flavin has a redox role in some other flavoproteins is not yet clear ((R)-2
      hydroxyacyl-CoA dehydratases, isopentenyl diphosphate isomerase and
      UDPgalactopyranose mutase). The remaining flavoenzymes do not make use of the
      redox properties of the flavin (acetohydroxyacid synthases and hydroxynitrile
      lyase). The literature is reviewed up to early 2002 and 121 references are cited.

PMID- 12521269
TI  - Pyrrolizidine alkaloids.
AB  - This review covers a range of pyrrolizidine alkaloids which have been isolated
      from various natural sources. The synthesis of necines and necic acids is
      described along with pharmacological and biological studies of pyrrolizidine
      alkaloids. The literature from July 2000 to June 2001 is reviewed, and 59
      references are cited.

PMID- 12521270
TI  - Developing services for children with cerebral palsy.

PMID- 12521271
TI  - Vitamin A for the treatment of children with measles--a systematic review.
AB  - Vitamin A deficiency is a recognized risk factor for severe measles. WHO and
      UNICEF have recommended vitamin A for the treatment of measles but there are
      children still dying from measles. A systematic review, including the use of meta
      analysis was done of randomized controlled trials comparing vitamin A with
      placebo obtained from a systematic search of the medical literature to determine
      whether vitamin A prevents mortality and pneumonia-specific mortality in children
      with measles. We identified five trials conducted in Africa, four in hospitals
      and one in a community that met the inclusion criteria. There were 445 children
      aged 6 months to 13 years supplemented with vitamin A and 478 with placebo. There
      was a 39 per cent reduction in overall mortality when vitamin A was used for the
      treatment of measles but this was not statistically significant (relative risk
      0.61; 95 per cent confidence interval 0.32-1.12). When stratified by dose, 200
      000 IU of vitamin A given for 2 days was associated with a reduction in overall
      mortality (0.36, 0.14-0.82) and pneumonia-specific mortality (0.33, 0.08-0.92) in
      hospitalized children in areas with high case fatality. Greater reduction in
      mortality was observed in children under the age of 2 years (0.17, 0.03-0.61). On
      the other hand, a single dose of 200 000 IU of vitamin A was not associated with
      reduced mortality (1.25, 0.48-3.1). There were no trials comparing a single dose
      with two doses of vitamin A. There were not enough studies to separate out the
      individual effects of age, dose, formulation, hospitalization and case fatality
      in the study area. We conclude that 200 000 IU of vitamin A repeated on 2 days
      should be used for the treatment of measles as recommended by WHO in children
      admitted to hospitals in areas where the case fatality is high.

PMID- 12521272
TI  - Ocular toxocariasis in a North Indian population.
AB  - Sera form 68 patients aged 1-30 years, suffering from posterior pole granuloma,
      peripheral granuloma, uveitis, endophthalmitis, optic neuritis and with a
      clinical diagnosis of suspected ocular toxocariasis, were tested for the presence
      of anti-Toxocara antibodies. Antibodies to Toxocara were detected in 11 (17 per
      cent) subjects less than 15 years old and three (4 per cent) subjects more than
      15 years of age using enzyme-linked immunosorbent assay. None of the controls
      sera (other helminthic diseases) were positive for anti-Toxocara antibody.

PMID- 12521273
TI  - Hymenolepis nana: a common cause of paediatric diarrhoea in urban slum dwellers
      in India.
AB  - The prevalence of intestinal parasitic infections was studied for a period of 5
      years (April 1996-April 2001) among urban slum dwellers. All age groups were
      represented in the study. Parasitological examinations were performed on 939
      faecal specimens collected on a household basis. The total prevalence of
      pathogenic parasites was 33.6 per cent. No significant age and sex differences in
      pathogenic parasites were observed. The prevalence of intestinal helminths and
      pathogenic protozoa was as follows: Hymenolepis nana (9.9 per cent), Ascaris
      lumbricoides (8.5 per cent), Giardia lamblia (8.4 per cent) and Entamoeba
      histolyticaldispar (3.7 per cent). Thirty-four E. histolytica/dispar positive
      samples were cultured and speciation was done using polymerase chain reaction
      (PCR). The predominant isolate was E. dispar compared to E. histolytica. The
      notable finding of the present study was high prevalence of Hymenolepis nana
      compared with other parasitic infections in slum dwellers.

PMID- 12521274
TI  - Randomized comparison of oxygen mask treatment vs. nasal continuous positive
      airway pressure in dengue shock syndrome with acute respiratory failure.
AB  - Dengue hemorrhagic fever (DHF) is caused by dengue virus. Patients with DHF grade
      3-4, termed Dengue Shock Syndrome (DSS), may develop acute respiratory failure
      after initial fluid resuscitation. Previously, these patients were treated with
      oxygen on a nasal cannula, or if necessary with tracheal intubation and
      mechanical ventilation. In the present prospective randomized study, we compared
      the effectiveness of oxygen treatment administered by a face mask vs. nasal
      continuous positive airway pressure (NCPAP). Morbidity, mortality, and supportive
      treatment was evaluated. Thirty-seven patients with DSS complicated by
      respiratory failure were enrolled. On admission and after 30 min of treatment,
      clinical and paraclinical data were obtained. Chest X-ray revealed pleural
      effusion in 92 per cent and showed interstitial oedema in 33 per cent. After 30
      min of treatment the respiratory rate decreased significantly in the NCPAP group
      (p < 0.05), while SaO2 and PaO2 increased in both groups (p < 0.01). However,
      subsequently a significant difference of unresponsiveness to treatment between
      the oxygen mask group and the NCPAP group (13/19 vs. 4/18,p < 0.01) was noted.
      Complications of NCPAP or oxygen mask treatment were not documented. We conclude
      that NCPAP is useful in improving the management of acute respiratory failure in
      children with DHF/DSS in dengue-endemic areas.

PMID- 12521276
TI  - Cystic fibrosis transmembrane regulator gene mutations in Bahrain.
AB  - A genotypic study was undertaken to characterize the cystic fibrosis
      transmembrane regulator gene mutations (CFTR) in the Bahraini cystic fibrosis
      (CF) population using a polymerase chain reaction-based direct gene test to
      search for 15 common CF mutations amongst Arabs. During the period October 2000
      to May 2001, 19 patients (12 males and seven females; aged at time of study
      between 4 months and 14 years with a mean age of 5.4 +/- 4.3 years) from 13
      families were recruited in the study. Patients were diagnosed as having CF, based
      on a typical clinical picture and sweat chloride levels > 60 mmol/l and were
      screened for CFTR mutations. The rate of consanguinity among the families was 77
      per cent. Eight mutations were detected in 21 of the 26 alleles examined. The
      overall detection rate was approximately 81 per cent. The allele frequency of the
      eight mutations was estimated to be approximately 73 per cent. There was no
      specific phenotypic pattern that correlated with a specific genotype. All
      families except two were of Bahraini origin. Of the eight mutations detected,
      four were common among Bahrainis (2043delG > 548A --> T > 4041C --> G =
      deltaF508, in order of decreasing frequency), accounting for 66 per cent of the
      Bahraini CF alleles. However, we also detected four different heterozygous
      mutations, namely: 1161delC, 1756G -->T, 3120 + 1G --> A, and 3661A --> T,
      accounting for 16 per cent of the Bahraini CF alleles.

PMID- 12521275
TI  - Disease progression markers during asymptomatic phase of HIV-1 infected children
      with unimpaired CD4+ cell values: evaluation of repeat CD4+ cell evaluation vs.
      other immunological parameters.
AB  - The availability of a marker that could predict the course of disease progression
      in HIV-infected individuals would be of considerable relevance during the
      asymptomatic stage in order to undertake timely prophylactic measures. A
      prospective study was undertaken in a group of 42 children suffering from
      thalassemia major with HIV-1 infection to assess the status of immune parameters,
      such as peripheral CD4+ T lymphocyte (CD4+ cell) percentage, delayed type of
      hypersensitivity (DTH) response to recall antigens, detection rate and levels of
      p24 antigen, and levels of beta-2 microglobulin and cytokines in serum. All were
      assessed at an interval of 2 years during the asymptomatic period, (baseline and
      follow-up assessments) in relation to the development of AIDS defining illness
      within a follow-up period of 3 years. No difference could be observed in the mean
      CD4+ cell percentage at baseline between those who progressed subsequently to
      develop AIDS within the follow-up period (progressors) and those who did not (non
      progressors). However, at the point of follow-up assessment the progressor group
      showed significantly lower CD4+ cell percentage compared to the non-progressor
      group (33 +/- 4.9 vs. 22 +/- 5.6; p < 0.05), although in the progressor group
      there was no correlation of the baseline and follow-up CD4+ cell percentage with
      the duration of the AIDS-free interval. However, in the progressor group there
      was a strong negative correlation between the rate of decline in CD4+ cell
      percentage and subsequent duration of the AIDS-free interval (r = -0.859).
      Analysis of additional immune parameters at baseline revealed that the progressor
      group, despite having CD4+ cell values comparable to non-progressors, showed
      impaired DTH response (number and total induration of positive responses being
      2.0 +/- 1.23 and 6.2 +/- 1.4 in the former group vs. 3.2 +/- 0.76 and 12.6 +/-
      3.80 in the later group; p < 0.05 for both the parameters), and elevated levels
      (mg/l) of serum beta-2 microglobulin (2.92 +/- 0.89 vs. 1.38 +/- 0.43; p < 0.05).
      The serum cytokine profile at baseline in the progressor group showed a T helper
      type-2 (Th2) dominant pattern, i.e. elevation of interleukin-4 (IL-4) and
      interleukin-10 (IL-10) levels with decreased levels of interleukin-2 (IL-2) and
      gamma interferon (gamma-IFN) compared to the non-progressor group that showed a T
      helper type-1 (Th1) dominant profile, i.e., elevation of IL-1 and gamma-IFN level
      with decreased levels of IL-4 and IL-10 (p < 0.05 for all four cytokines). The
      present study points out that rate of decline rather than single point of
      assessment of CD4+ cell values is a more reliable predictor for disease
      progression in HIV-1 infected children. In addition, parameters such as DTH
      response, serum levels of beta-2 microglobulin and serum cytokine profile, may
      provide valuable predictors of subsequent fall in CD4+ cell value.

PMID- 12521277
TI  - Comparisons of oral calcium, high dose vitamin D and a combination of these in
      the treatment of nutritional rickets in children.
AB  - Nutritional rickets remains a common child health problem in Turkey and many
      other developing countries. Although vitamin D deficiency is accepted as the
      basic problem underlying the disease, others postulate that a deficiency of
      dietary calcium, rather than vitamin D, is often responsible for the nutritional
      rickets in sunny countries. We conducted a placebo-controlled study to determine
      the best treatment regimen for nutritional rickets in children residing in lower
      socioeconomic regions of a sunny city, Istanbul. Forty-two infants (aged 6-30
      months) with rickets were divided into three groups and included in the study. In
      a randomized fashion vitamin D (300 000 units, intramuscularly), calcium lactate
      (3 g daily) or a combination of vitamin D and calcium were given to the children.
      Alkaline phosphatase, calcium, albumin, ionized calcium and phosphorus levels
      were measured each week. X-ray examinations of the left wrist and left knee were
      undertaken at the beginning of the study and were repeated at the 2nd and 4th
      weeks and were scored in order to assess the response to treatment. Treatment
      produced an increase in serum calcium and a decrease in alkaline phosphatase
      concentration in all three groups, but the most important increase was reached in
      the vitamin D plus calcium group. We conclude that vitamin D deficiency appears
      to be the primary etiologic factor of rickets in our study group, but a better
      response to treatment with vitamin D or in combination with calcium was obtained
      than to treatment with calcium alone.

PMID- 12521278
TI  - Safety evaluation of MMR vaccine during a primary school campaign in Saudi
      Arabia.
AB  - Monitoring of adverse events following the administration of MMR vaccine
      containing the Urabe mumps virus vaccine strain, to over 2 million schoolchildren
      (aged 6-13 years) revealed that the incidence of vaccine-associated aseptic
      meningitis was one case per 295 000 doses given. About 92 per cent of these
      children had had their primary immunization against MMR at 12 months of age and,
      therefore, were probably not immunologically naive. It appears from our data that
      the use of the Urabe-based mumps vaccine in the booster-dose format induces much
      less adverse effects than usually observed following the primary immunization
      with it. Further studies are needed to prove this conclusively.

PMID- 12521279
TI  - Urinary tract infection in severely malnourished children at the University of
      Maiduguri Teaching Hospital.
AB  - One hundred and ninety-four children with severe protein energy malnutrition were
      investigated for urinary tract infection in this prospective study. The
      prevalence of urinary tract infection was found to be 11.3 per cent. There was no
      difference either between the sexes or the different categories of malnutrition.
      The commonest isolates were Gram-negative organisms predominantly Escherichia
      coli. The antibiotic sensitivity pattern of the organisms in this study differs
      from other reports. In this study, we observed poor sensitivities of organisms
      especially the Gram negatives to the second and third generation cephalosporins.
      We therefore conclude that regular surveillance of urinary tract infection
      pathogens and their antibiotic sensitivity patterns should be carried out.

PMID- 12521281
TI  - Blood pressure, hematologic and erythrocyte fragility changes in children
      suffering from sickle cell anemia following ascorbic acid supplementation.
AB  - The effect of ascorbic acid supplementation (100 mg/day for 6 weeks) on blood
      pressure, packed cell volume, irreversibly sickled cells, per cent fetal
      hemoglobin, hemoglobin concentration, and erythrocyte osmotic fragility was
      assessed in children suffering from sickle cell anemia. Fifteen children whose
      ages ranged from 4 to 11 years (7.5 +/- 0.75 years) were studied. Ascorbic acid
      supplementation reduced systolic blood pressure by 10.9 +/- 3.4 mmHg (p < 0.01),
      diastolic blood pressure by 7.3 +/- 2.0 mmHg (p < 0.01) and mean arterial
      pressure by 9.4 +/- 2.6 mmHg (p < 0.01). It significantly increased packed cell
      volume (p < 0.001), hemoglobin concentration (p < 0.001) and per cent fetal
      hemoglobin (p < 0.001), but reduced per cent irreversibly sickled cells (p <
      0.001). Ascorbic acid supplementation also abolished the long tail of the
      erythrocyte osmotic fragiligram and increased the resistance of the cells to
      lysis.

PMID- 12521280
TI  - Prognostic factors in childhood tuberculous meningitis.
AB  - The risk factors affecting the outcome in 50 children with tuberculous meningitis
      were evaluated over a period of 20 months. Five children (10 per cent) had stage
      1 disease, 29 (58 per cent) had stage II disease, and 16 (32 per cent) had stage
      III disease at admission. Seventeen cases (34 per cent) showed complete recovery,
      five (10 per cent) had mild, 14 (28 per cent) had moderate, and nine (18 per
      cent) had severe neurological sequelae. Five children (10 per cent) died. Younger
      age, tonic posturing, papilloedema, focal neurological deficit and stage at
      presentation were found to affect adversely the prognosis independently in
      children with tuberculous meningitis.

PMID- 12521282
TI  - User fees impact access to healthcare for female children in rural Zambia.
AB  - The World Bank and International Monetary Fund favor healthcare user fees. User
      fees offer revenue and may decrease inappropriate care. However, user fees may
      deter needed care, especially in vulnerable populations. A cross-sectional
      analysis of healthcare utilization in a large Zambian hospital was conducted for
      children 3-6 years of age during a 1-month observation period. Diagnoses and
      treatments were compared using paired t-tests. Chi-squared tests compared
      outpatient service use. The relative risk of admission was determined for each
      stratum. Logistic models were developed to evaluate the impact of age, gender,
      and the age-gender interaction on hospital admissions. Trends suggest female
      children may be less likely to present for care when user fees are imposed.
      However, treatment type, treatment number, and number of diagnoses did not differ
      between genders. The relative risk of admission was highest for males 5-6 years
      old. Neither age nor gender alone was a significant determinant of hospital
      admission. However, the age-gender interaction was significant with female
      admissions least likely when costs were incurred. We conclude that user fees
      appear to decrease differentially utilization of inpatient care for female
      children in rural Zambia.

PMID- 12521284
TI  - Increased heights and weights of Isfahani female children and adolescents in
      Iran.
AB  - Considering the different patterns of growth in various societies, an
      anthropometric evaluation of 6-18-year-old female students was carried out in
      1997 in Isfahan, Iran with the goal of establishing height and weight values for
      use in clinical settings. 4638 female Isfahani students aged 6-18 years were
      selected by a random cluster sampling. Their height (cm) and weight (kg) were
      measured and the related percentiles were determined. The results were compared
      with previous studies in Iran using Student's t-test. Findings show an increase
      of 6-12 cm in height and of 1-4 kg in weight of Isfahani female 6-18-year-old
      students as compared with a similar study in 1975. The height curves can be
      approximately superposed on those of NCHS growth charts, but American girls are
      significantly heavier than Isfahani girls after the age of 14. The growth
      parameters among Isfahani female students have improved compared with those of
      their compatriots and also their fellow citizens 22 years earlier. Improvements
      in nutrition, health services or other unknown environmental factors may have
      contributed to an increase in the growth indexes.

PMID- 12521283
TI  - Bacteremia in childhood cancer.
AB  - Infection-related mortality affects the overall survival rates of children who
      are receiving treatment for cancer. The leading cause of mortality is bacteremia
      and sepsis related to it in febrile neutropenic patients. All positive blood
      cultures of febrile neutropenic patients treated in the Department of Pediatric
      Hematology-Oncology, Cerrahpasa Medical School, between January 1995 and January
      2001 were reviewed. Cultures grew 159 micro-organisms, 95 (60 per cent) of which
      were Gram-positive bacteria, 56 (35 per cent) were Gram-negative bacteria and
      eight (5 per cent) were fungi. Coagulase-negative staphylococci (63, 40 per cent)
      and S. aureus (8, 5 per cent) were the most frequent Gram-positive pathogens.
      Klebsiella, E. coli, Enterobacter and Pseudomonas infections were the primary
      Gram-negative pathogens. Twenty cases were lost because of sepsis: in 11 cases
      (55 per cent) Gram-negative bacteria, in eight cases (40 per cent) Gram-positive
      bacteria, and in only one case a fungus were the causative organisms. Although
      vancomycin was not included in the first-line treatment, the mortality rate of
      Gram-positive bacteremia was 8 per cent. In Gram-negative bacteremia it was 20
      per cent. Gram-negative pathogens, which were resistant to multiple antibiotics,
      caused the mortality. Drug resistance and mortality due to micro-organisms must
      be taken into consideration while febrile neutropenia protocols are prepared.

PMID- 12521286
TI  - Combining photolysis and bioprocesses for mineralization of high molecular weight
      polyacrylamides.
AB  - The influence of ultraviolet photolysis as a pretreatment to the aerobic and
      anaerobic biological mineralization of a 14C-polyacrylamide was assessed using a
      series of radiorespirometry bioassays. The polyacrylamide studied was non-ionic
      with molecular weights ranging between 100,000 and 1 million. Aerobic and
      anaerobic biomineralization of the unphotolysed (raw) polyacrylamide was found to
      be only 0.60% and 0.70%, respectively, after 6 weeks of incubation, and hence
      indicative of the natural recalcitrance of polyacrylamide to microbial
      degradation. The effectiveness of UV irradiation in the physical breakdown of the
      polyacrylamide chain into oligomers was demonstrated by the shift in the
      molecular weight distribution and the positive correlation between the time of
      irradiation and the degree of its biological mineralization. The molecular weight
      fraction below 3 kD, which represents only 2% of the raw polyacrylamide, was
      increased to 41, 60 and 80% after 12, 24 and 48 hours of photolysis,
      respectively. This in turn, yielded, after 6 weeks of incubation, an aerobic
      mineralization of 5, 17 and 29% of 150 mg/L polyacrylamide, respectively, and an
      anaerobic mineralization of 3, 5 and 17%, respectively. Biomass acclimation
      substantially improved the specific initial rate of biomineralization of the
      photolysed polyacrylamides, but not the overall percentage of polyacrylamides
      mineralized.

PMID- 12521285
TI  - Proximal muscle weakness--an unusual presentation of celiac disease.
AB  - The identification of the etiology of metabolic bone disease that leads to
      myopathy is important as this type of muscle weakness often responds fully to
      treatment. We present the case history of an 11-year-old girl with celiac disease
      who had rickets masquerading as muscle weakness and bone pains.

PMID- 12521287
TI  - Biotransformation of naphthalene and diaryl ethers by green microalgae.
AB  - The role of green microalgae in the biotransformation of naphthalene (a
      polycyclic aromatic hydrocarbon) and diaryl ethers was investigated using axenic
      cultures of Chlorella vulgaris and two environmental isolates, Scenedesmus SI1
      and Ankistrodesmus SI2. Biotransformation experiments with dense cell cultures
      showed that these three green algae transformed toxic xenobiotics to more polar
      metabolites. Chlorella vulgaris metabolized naphthalene to 1-naphthol (0.36
      0.65%). Ankistrodesmus SI2 biotransformed dibenzofuran to six metabolites (total
      over 7%), three of which (possibly four) were identified as monohydroxylated
      dibenzofurans, the remaining two may be dihydroxylated derivatives. Scenedesmus
      SI1 biotransformed dibenzo-p-dioxin to three metabolites, one of which was
      tentatively identified as 2-hydroxydibenzo-p-dioxin (approximately 3.8%), the
      remainder may be dihydroxylated derivatives. This is the first time that the
      biotransformation of diaryl ethers by green microalgae has been investigated.

PMID- 12521288
TI  - Mathematical modeling of precipitation and dissolution reactions in
      microbiological systems.
AB  - We expand the biogeochemical model CCBATCH to include a precipitation/dissolution
      sub-model that contains kinetic and equilibrium options. This advancement extends
      CCBATCH's usefulness to situations in which microbial reactions cause or are
      affected by formation or dissolution of a solid phase. The kinetic option employs
      a rate expression that explicitly includes the intrinsic kinetics for reaction or
      mass-transport control, the difference from thermodynamic equilibrium, and the
      aqueous concentration of the rate-limiting metal or ligand. The equilibrium
      feature can be used alone, and it also serves as check that the kinetic rate
      never is too fast and "overshoots" equilibrium. The features of the expanded
      CCBATCH are illustrated by an example in which the precipitation of Fe(OH)3(s)
      allows the biodegradation of citric acid, even though complexes are strong and
      not bioavailable. Precipitation releases citrate ligand, and biodegradation of
      the citrate increases the pH.

PMID- 12521289
TI  - Application of a reverse transcription-PCR assay to monitor regulation of the
      catabolic nahAc gene during phenanthrene degradation.
AB  - Biodegradation of polycyclic aromatic hydrocarbons (PAH), such as phenanthrene,
      in environmental samples is often limited by low bioavailability which results
      from a combination of low aqueous solubility and/or high sorption. The purpose of
      this study was to investigate the influence of agents that increase PAH
      bioavailability on expression of the PAH catabolic gene nahAc. Phenanthrene was
      used as a model PAH and Pseudomonasputida PpG7, which contains the NAH7 plasmid
      that encodes the genes responsible for naphthalene and phenanthrene degradation,
      was used as a model degrader. PAH bioavailability was altered by the addition of
      two biosurfactants, rhamnolipid and hydroxypropyl-beta-cyclodextrin (HPCD). Gene
      expression was determined by extraction of bacterial mRNA followed by RT-PCR
      amplification of two transcripts; nahAc, a naphthalene dioxygenase gene, and
      rpoD, a housekeeping gene. Results indicate that the lag period preceding nahAc
      gene induction decreased from 312 to 48 h in the presence of biosurfactants.
      Expression of the nahAc gene, as measured by RT-PCR, in the presence of
      surfactants was bimodal on a temporal basis, indicating that induction stopped
      briefly during biodegradation. Cessation of induction could have resulted from
      the up-regulation of alternate pathways or the accumulation of toxic
      intermediates. In contrast, expression of the rpoD gene was maintained throughout
      the duration of each experiment. This research demonstrates that the use of a
      gene expression assay to monitor the impact of substrate bioavailability on
      substrate utilization provides unique information concerning the biodegradation
      process that cannot be obtained from more traditional biodegradation assays such
      as cell growth or substrate disappearance. Gene expression assays also have the
      potential for use in assessing the impact of other environmental factors on
      biodegradation.

PMID- 12521290
TI  - Mesophilic and thermophilic activated sludge post treatment of anaerobic
      effluent. Sludge and wastewater characterisation using batch experiments.
AB  - Anaerobic pretreated paper process water was characterized in terms of readily
      biodegradable, slowly biodegradable, very slowly biodegradable and inert
      wastewater fractions under mesophilic and thermophilic conditions. The anaerobic
      pretreated paper process water contained a relatively high amount of slowly
      biodegradable components and few easily biodegradable components as indicated by
      the ratio of short-term BOD over the BOD5. Wastewater readily biodegradable COD,
      determined as short-term BOD, was almost similar when measured under both
      temperature conditions. Fractions of slowly biodegradable COD and inert COD of
      the same wastewater were found to depend on the type of biomass involved in the
      test. Thermophilic aerobic biomass was not able to degrade the wastewater to the
      same extent as the mesophilic biomass resulting in higher apparent inert COD
      levels. Furthermore, wastewater colloidal COD did not flocculate under
      thermophilic conditions and was thus not removed from the liquid phase.

PMID- 12521291
TI  - Degradation of petroleum model compounds immobilized on clay by a hypersaline
      microbial mat.
AB  - In this study the degradation of hydrophobic petroleum model compounds
      (phenanthrene, pristane, octadecane and dibenzothiophene) added to a submersed
      hypersaline microbial mat was investigated. Montmorillonite with an artificially
      altered, hydrophobic surface was used as carrier material, forming an organo-clay
      complex (OCC) with the attached mixture of petroleum model compounds. 6 mg/cm2
      OCC were applied to cyanobacterial mat pieces, containing approximately 33.3
      microg/mg OCC of each compound. The degradation experiment was performed under
      controlled laboratory conditions and accompanied by chemical analyses by GC/GC
      MS, molecular analyses by PCR and DGGE as well as functional analyses by
      microsensor measurements of oxygen, photosynthesis, sulfide, pH and light. All
      applied model compounds were degraded, but residues were still present after 18
      weeks. The aromatic compounds phenanthrene (5.1 microg/mg OCC) and
      dibenzothiophene (4.3 microg/mg OCC) were preferentially degraded compared to the
      alkanes pristane (12.4 microg/mg OCC) and n-octadecane (13.4 microg/mg OCC).
      Metabolic changes during the degradation process could not be detected by
      microsensor measurements. The molecular population analyses did not reveal any
      significant community changes concomitant with the decrease of the petroleum
      model compounds. We conclude, that the pristine mats represent an intact, robust
      ecosystem in which the enzymatic requirements for the degradation of the applied
      pollutants exist. The slow degradation process did not affect the usual high
      internal turnover rates and did not favor a certain population in the community
      of the mats.

PMID- 12521292
TI  - Microbial activity in soils following steam treatment.
AB  - Steam enhanced extraction (SEE) is an aquifer remediation technique that can be
      effective at removing the bulk of non-aqueous phase liquid (NAPL) contamination
      from the subsurface, particularly highly volatile contaminants. However, low
      volatility compounds such as polynuclear aromatic hydrocarbons (PAHs) are less
      efficiently removed by this process. This research evaluated the effects of steam
      injection on soil microbial activity, community structure, and the potential for
      biodegradation of contaminants following steam treatment. Three different soils
      were evaluated: a laboratory-prepared microbially-enriched soil, soil from a
      creosote contaminated field site, and soil from a chlorinated solvent and waste
      oil contaminated field site. Results from field-scale steaming are also
      presented. Microbial activity before and after steam treatment was evaluated
      using direct epifluorescent microscopy (DEM) using the respiratory activity dye 5
      cyano-2,3, ditolyl tetrazolium chloride (CTC) in conjunction with the
      fluorochrome 5-(4,6-dichlorotriazinyl) aminofluorescein (DTAF) to yield a
      quantitative assessment of active and total microbial numbers. DEM results
      indicate that steamed soils that were analyzed while still hot exhibited
      microbial activity levels that were below detection. However, soil samples that
      were slowly cooled, more closely reflecting the conditions of applied SEE,
      exhibited microbial activity levels that were comparable to presteamed soils.
      Samples from a field-site where steam was applied continuously for 6 weeks also
      showed high levels of microbial activity following cooling. The metabolic
      capabilities of the steamed communities were investigated by measuring cell
      growth in enrichment cultures on various substrates. These studies provided
      evidence that organisms capable of biodegradation were among the mesophilic
      populations that survived steam treatment. Fluorescent in situ hybridization
      (FISH) analysis of the soils with domain-level rRNA probes suggest that both
      Archaea and Bacteria survived steam exposure.

PMID- 12521293
TI  - The control of mRNA stability in response to extracellular stimuli.
AB  - Regulated mRNA turnover is a highly important process in control of gene
      expression. The specific sequence elements in mRNA modulate the stability of
      different mRNAs, which varies considerably in response to extracellular stimuli.
      But the mechanistic basis for regulation of mRNA turnover remains nebulous.
      Recent works indicate that several signaling pathways have been implicated in
      regulating the decay of specific mRNA and certain ARE binding proteins mediate
      rapid degradation of the mRNAs. This review provides a current knowledge of
      diverse extracellular signals contributing to stabilization of short-lived mRNA.

PMID- 12521294
TI  - Different mechanisms for membrane and nuclear damages in apoptosis induced by an
      immunosuppressant, FTY720.
AB  - A novel immunosuppressant, FTY720, that was purified from cultures of Isaria
      sinclairii has been shown to cause apoptosis of lymphocytes, but its biochemical
      and molecular mechanisms are largely unknown. In this study, we investigated the
      signal transduction of FTY720-induced apoptosis in comparison with the Fas
      induced apoptosis. Although FTY720 induced nuclear and membrane damages in a dose
      dependent manner, nuclear damage, but not membrane damage, was suppressed by the
      caspase-3 inhibitor, DEVD-FMK. It blocked both the nuclear and membrane damages
      that were induced by the anti-Fas antibody. Experiments using enucleated
      cytoplasts also demonstrated that membrane damage was induced by FTY720. However,
      the ones that were induced by the anti-Fas antibody were not blocked by DEVD-FMK.
      Exogenously-added sphingolipids partially suppressed the FTY720-induced membrane
      damage. These results suggest that FTY720 induces membrane damage through the
      caspase-3-independent pathway that is modulated by sphingolipids.

PMID- 12521296
TI  - MAPK signaling is involved in camptothecin-induced cell death.
AB  - Camptothecin, a topoisomerase I inhibitor, is a well-known anticancer drug.
      However, its mechanism has not been well studied in human gastric cancer cell
      lines. Camptothecin induced apoptotic cell death in human gastric cancer cell
      line AGS. Z-VAD-fmk, pan-caspase inhibitor, blocked apoptotic phenotypes induced
      by camptothecin suggesting that caspases are involved in camptothecin-induced
      cell death. An inhibitor of caspase-6 or -8 or -9 did not prevent cell death by
      camptothecin. Various protease inhibitors failed to prevent camptothecin-induced
      cell death. These results suggest that only few caspases are involved in
      camptothecin-induced cell death. Camptothecin induced phosphorylation of ERK1/2,
      JNK, and p38 MAPK, in a dose and time-dependent manner in AGS. Z-VAD-fmk did not
      affect MAPK signaling induced by camptothecin suggesting that caspase signaling
      occurs downstream of MAPK signaling. Blocking of p38 MAPK, but not ERK1/2,
      resulted in partial inhibition of cell death and PARP cleavage by camptothecin in
      AGS. Taken together, MAPK signaling is associated with apoptotic cell death by
      camptothecin.

PMID- 12521297
TI  - Expression of steroidogenic acute regulatory protein mRNA in rat placenta during
      mid-late pregnancy.
AB  - The production of a steroid hormone in the placenta is essential for maintaining
      the pregnancy and developing the fetus during gestation. In various steroidogenic
      tissues (including gonads and adrenal cortex), the steroidogenic-acute-regulatory
      protein (StAR) acutely transfers cholesterol from the outer to the inner
      mitochondrial membrane for rapid steroidogenesis. Although steroid hormones were
      synthesized in the rat placenta, the developmental expression of StAR has been
      poorly understood in the rat placenta during mid-late pregnancy. Therefore, the
      aim of the present study was to establish the expression and localization of StAR
      mRNA in the rat placenta during mid-late pregnancy using Northern blots and in
      situ hybridization. The Northern blot analysis showed that the StAR mRNA
      expression significantly changed as the gestation day (GD) progressed. The
      placental expression of StAR mRNA increased between GD 11 and 13, and then
      slightly decreased until term. In situ hybridization showed a strong StAR
      expression in giant trophoblast cells on GD 11 and 13, and a moderate expression
      in trophoblast and stroma cells within the villi of the labyrinth zone throughout
      the pregnancy. In this study, we reveal for the first time the existence of StAR
      mRNA in steroidogenic cells of the placenta during mid-late pregnancy. In
      conclusion, our results suggest that StAR may regulate steroidogenesis in the rat
      placenta to maintain the pregnancy and developing the fetus.

PMID- 12521295
TI  - Effects of MK-801 and CNQX on various neurotoxic responses induced by kainic acid
      in mice.
AB  - Effects of MK-801 (a NMDA receptor blocker) and CNQX (6-cyano-7-nitroquinoxaline
      2,3-dione; a non-NMDA receptor blocker) on several neurotoxic responses induced
      by kainic acid (KA) were examined in ICR mice. In a lethality test,
      intracerebroventricular (i.c.v.) pretreatment of MK-801 (1 microg), but not CNQX
      (0.5 microg), attenuated the time to lethality induced by KA (0.5 microg)
      administered i.c.v. In the memory test (a passive avoidance test), MK-801, but
      not CNQX, prevented the memory loss induced by KA (0.1 microg). The damage
      induced by KA (0.1 microg) administered i.c.v. in the hippocampus was markedly
      concentrated in the CA3 pyramidal neurons. Both MK-801 and CNQX blocked the
      pyramidal cell death in CA3 hippocampal region induced by KA. In the
      immunocytochemical study, KA dramatically increased the phosphorylated ERK (p
      ERK) and decreased the phosphorylated CREB (p-CREB) in the hippocmapus. Both MK
      801 and CNQX attenuated, in part, the increased p-ERK and the decreased p-CREB
      induced by KA. In addition, both MK-801 and CNQX partially reduced the increased
      c-Fos and c-Jun protein expression in hippocampus induced by KA. Our results
      suggest that both NMDA and non-NMDA receptors are involved in supraspinally
      administered KA-induced pyramidal cell death in CA3 region of hippocampus in the
      mouse and the p-ERK and the dephosphorylation of CREB protein may play an
      important role in CA3 region cell death of the hippocampus induced by KA
      administered supraspinally. Furthermore, c-Fos and c-Jun proteins may serve as
      third messengers responsible for CA3 pyramidal cell death induced by
      supraspinally administered KA.

PMID- 12521298
TI  - Morphology of calretinin-immunoreactive neurons in the superficial layers of
      hamster superior colliculus after enucleation: lack of co-localization with GABA.
AB  - We recently reported on the distribution and effects of eye enucleation on the
      immunoreactivity of calretinin in the superficial layers of the hamster superior
      colliculus (SC). In the present study, we describe the types of labeled cells and
      compare this labeling to that of GABA, the major inhibitory neurotransmitter in
      the central nervous system. An almost complete depletion of calretinin
      immunoreactive (IR) fibers in the superficial layers of the contralateral SC was
      found following unilateral enucleation. On the contralateral SC, many calretinin
      IR cells were newly appeared. The majority of the newly-appeared cells had small-
      to medium-sized round, oval, or vertical fusiform cell bodies. Two-color
      immunofluorescence revealed that none of these newly-appeared cells were labeled
      with an antibody to GABA. The present results show that the calretinin-IR cells
      are unique in the superficial hamster SC when compared to most of the other brain
      areas, where many calretinin-IR cells are GABAergic interneurons.

PMID- 12521299
TI  - Ex vivo expansion and clonality of CD34+ selected cells from bone marrow and cord
      blood in a serum-free media.
AB  - Although umbilical cord blood is increasingly being used in allogeneic marrow
      transplantation, delayed platelet engraftment is often a concern for cord blood
      transplant recipients. We evaluated the potential of ex vivo expansion and
      clonality in CD34+ cells separated from a bone marrow source, and cord blood, in
      a serum-free Media. The CD34+ cells, selected from bone marrow (BM) and umbilical
      cord blood (CB), were expanded with hematopoietic growth factors. They were then
      cultured for burst-forming units of erythrocytes (BFU-E), colony-forming units of
      granulocytes and monocytes (CFU-GM) and colony-forming units of megakaryocytes
      (CFU-Mk) at days 0, 4, 7, and 14 under the combination of growth factors, with
      cell counts. The cytokines included the recombinant human megakaryocyte growth
      and development (100 ng/ml), interleukin-3 (10 ng/ml), stem cell factor (100
      ng/ml), flt-3 ligand (50 ng/ml) and interleukin-11 (200 ng/ml). The CB-selected
      CD34+ cells showed significantly higher total cell expansion than those from the
      BM at day 7 (3.0 fold increase than BM), day 14 (2.4 fold), and day 17 (2.6
      fold). The colony count of the BFU-E/CFU-E per CD34+ cell at day 0 was 0.14 +/-
      0.023 in the CB, which was significantly higher than 0.071 +/- 0.015 in the BM.
      The CB-selected CD34+ cells produced more BFU-E colonies than the BM on culture
      days 4, 7, and 14. The BFU-E colonies from the CB cells increased markedly on
      culture days 4 and 7, with a 4-fold increase at day 14. The colony count of the
      CFU-Mk per CD34+ cell at day 0 was 0.047 +/- 0.011 in the CB-selected CD34+ cells
      cultures, which was higher than the 0.026 +/- 0.014 in the BM. The CB-selected
      CD34+ cells produced more CFU-Mk colonies than the BM on culture days 4, 7 and
      14. In conclusion, the ex vivo expansion of the CB cells may be very promising in
      producing total cellular expansion, CFU-Mk and BFU-E compared with BM, especially
      at day 7. The ex vivo expansion of the CB may have rationale in making an ex vivo
      culture for 7 to 14 d.

PMID- 12521300
TI  - Expression, purification, and crystallization of glutamyl-tRNA(Gln) specific
      amidotransferase from Bacillus stearothermophilus.
AB  - Although the genes that encode the glutamyl-tRNA(Gln) (Glu-tRNA(Gln)) specific
      amidotransferase (Glu-AdTase) from various bacteria and eukaryotic organelles are
      known, the precise mechanism of the enzyme is still unclear. One of the reasons
      is that there is no information on the three-dimensional structure of the
      complex, the Glu-AdTase:Glu-tRNA(Gln):ATP:amino group donor. To obtain the
      crystals of Glu-AdTase, the Glu-AdTase of Bacillus stearothermophilus was
      overexpressed and purified after cloning of the gene that encodes the enzyme. The
      cloned DNA contained the full-length gene cluster that represented the Glu-AdTase
      of B. stearothermophilus, and was organized as an operon that consisted of three
      open-reading frames (ORFs). The order of the genes was gatCAB, as shown in
      Bacillus subtilis. The ORFs showed a high amino-acid homology to those of B.
      subtilis (A subunit, 73.2%; B subunit, 81.6%; C subunit, 69.5%) and
      Staphylococcus aureus (A subunit, 61.9%; B subunit, 71.8%; C subunit, 45.9%). The
      ORFs were re-cloned on the overexpression vector, pTrc99a, and a recombinant
      pTrcgatCABBST was obtained. The Glu-AdTase that was overexpressed with
      pTrcgatCABBST in Escherichia coli retained transamidation activity on the
      mischarged glutamic acid on the tRNA(Gln). It also produced correctly-charged Gln
      tRNA(Gln) at 37, 42, and 50 degrees C. Although Glu-AdTases from both B. subtilis
      and B. stearothermophilus were subjected to crystallization, the micro-crystals
      were only obtained from the B. stearothermophilus enzyme.

PMID- 12521301
TI  - Gene expression profile analysis in human hepatocellular carcinoma by cDNA
      microarray.
AB  - We performed gene expression profiling of normal and hepatocellular carcinoma
      (HCC) liver tissues using a high-density microarray that contained 3,063 human
      cDNA. The results of a microarray hybridization experiment from eight different
      HCC tissues were analyzed and classified by the Cluster program. Among these
      differentially-expressed genes, the galectin-3, serine/threonine kinase SGK,
      translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and
      ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the
      insulin-like growth factor binding protein-3 were down-regulated in HCC. The
      differential expression of these genes was further confirmed by an RT-PCR
      analysis. In addition, our data suggest that the gene expression profile of HCC
      varies according to the histological types.

PMID- 12521302
TI  - In vivo import experiments in protoplasts reveal the importance of the overall
      context but not specific amino acid residues of the transit peptide during import
      into chloroplasts.
AB  - The N-terminal transit peptide of chloroplast proteins is necessary and
      sufficient to direct proteins to the chloroplasts. However, the requirement of
      the transit peptide of chloroplast proteins is not fully understood. In this
      study we investigated the requirement of a transit peptide at the level of amino
      acid sequence using an in vivo targeting approach. Targeting experiments with
      green fluorescent protein (GFP) fusion proteins containing varying lengths of the
      N-terminal region of the small subunit of rubisco complex (RbcS) revealed that at
      least 73 amino acid residues of the N-terminal region is required to direct GFP
      to the chloroplasts without affecting the efficiency. Even a small deletion from
      the C- or N-termini of the minimal length of the transit peptide results in
      strong inhibition of targeting. Also, a small internal deletion within the
      minimal transit peptide strongly affected targeting of GFP fusion proteins.
      However, when we replaced one or two amino acid residues of the transit peptide
      with corresponding numbers of alanine residues sequentially, all the mutants were
      imported into chloroplasts with 80 to 100% efficiency. Together these results
      suggest that the overall context of amino acid sequence, but not any specific
      amino acid residue, of the transit peptide is critical for targeting to the
      chloroplasts.

PMID- 12521303
TI  - Herpes simplex virus type 1 glycoprotein D inhibits T-cell proliferation.
AB  - Herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) binds to its cellular
      receptor, herpesvirus entry mediator (HVEM), to enter into activated T cells.
      Since gD is expressed on the cell surface of activated T cells after infection
      and can interact with HVEM, a co-stimulatory molecule for T cells, we
      hypothesized that the membrane-bound gD can exert an immunomodulatory effect on
      activated T cells. In this report, we demonstrated the following: (1) The gD
      expression was detected on the cell surface of activated T cells after HSV-1
      infection. (2) Recombinant soluble gD protein or gD-expressing mouse fibroblasts
      inhibited T-cell proliferation that was induced by OKT3 [anti-CD3 monoclonal
      antibody (mAb)]. (3) The co-expression of gD and HVEM resulted in the inhibition
      of the nuclear factor (NF)-kappaB activation that was induced by the HVEM
      overexpression. Taken together, our results suggest that the inhibitory effect of
      gD may be due to its ability to actively inhibit the signaling pathway that is
      mediated by HVEM on the cell surface level, which may be a novel immune evasion
      mechanism that is utilized by HSV-1.

PMID- 12521304
TI  - Identification of non-telomeric G4-DNA binding proteins in human, E. coli, yeast,
      and Arabidopsis.
AB  - G4-DNA binding proteins of E. coli, Saccharomyces cerevisiae, Arabidopsis, and
      human have been identified by a synthetic non-telomeric G4-DNA oligo 5'
      d(ACTGTCGTACTTGATATGGGGGT)-3' using gel mobility shift assays. G4-DNA binding
      proteins are specific to G4-DNA, a four-stranded guanine-DNA structure. Bound
      complexes of G4-DNA and proteins were identified in nuclear extracts of all
      examined organisms in this study. In humans, three different G4-DNA and protein
      complexes were identified. However, human telomeric G-quadruplex oligo did not
      compete with G4-DNA oligo in the competition assays, suggesting that the
      identified G4-DNA binding proteins may be different from the known human
      telomeric G4-DNA binding proteins. We discovered two complexes of G4-DNA and
      protein in Arabidopsis identified in mobility shift assays. Interestingly, two
      complexes of G4-DNA and proteins were identified from E. coli, which have a
      circular genomic DNA structure. Results of this investigation suggest that non
      telomeric G4-DNA structure and its binding proteins may be involved in important
      functional roles in both prokaryotes and eukaryotes.

PMID- 12521305
TI  - Mutations induced by 1,3-butadiene metabolites, butadiene diolepoxide, and
      1,2,3,4-diepoxybutane at the Hprt locus in CHO-K1 cells.
AB  - Butadiene (BD) is an important industrial chemical that is classified as a
      probable human carcinogen. Butadiene diolepoxide (BDE) and 1,2,3,4-diepoxybutane
      (DEB) are metabolites of carcinogenic BD and contain the DNA-reactive one and two
      epoxides, respectively. In this study, the mutation frequencies and mutation
      spectra that are induced by BDE and DEB have been investigated at the hprt locus
      in CHO-K1 cells. The BDE- and DEB-treated CHO-K1 cells were allowed to grow for
      several days, then seeded in a medium that contained 6-thioguanine in order to
      select the hprt mutants. BDE exhibited the mutagenic activity at concentrations
      that were approximately 100-times higher than DEB. The mutation spectra for BDE
      and DEB were determined by a reverse transcription-polymerase chain reaction of
      hprt mRNA, which was followed by automatic DNA sequencing of the PCR products.
      The mutational spectrum for BDE was exon deletions (16/41), G x C --> A x T
      transitions (11/41), and A x T --> G x C transitions (5/41). The mutational
      spectrum for DEB was exon deletions (15/39), G x C --> A x T transitions (11/39),
      and A x T --> T x A transversions (5/39). The most common base substitution that
      was induced by both BDE and DEB was G x C --> A x T transitions. The sites of the
      single base substitutions that were induced by BDE and DEB were guanine and
      adenine, which was consistent with the DNA adduct profiles. The high frequencies
      of the exon deletions by each metabolite occurred in the regions of exons 2, 3,
      or 4. These data indicate that BDE and DEB are mutagenic carcinogens by forming
      DNA adducts at the site of adenine and guanine, and inducing large exon deletions
      and single base substitutions.

PMID- 12521306
TI  - RACK-1, a receptor for activated C kinase, interacts with the transcription
      factor NFAT and represses its transactivation.
AB  - To isolate and characterize a novel protein that interacts with nuclear factor of
      activated T cells (NFAT) and potentially regulates its activity, we screened a
      Jurkat cDNA library by using the NFAT regulatory domain as bait in the yeast two
      hybrid system. RACK-1, a receptor for activated protein kinase C and a homologue
      of the G-protein beta subunit, was identified as a NFAT-binding protein.
      Mammalian two hybrid tests in CV-1 cells and a coimmunoprecipitation assay
      confirmed protein-protein interaction between NFAT and RACK-1. In addition,
      overexpression of RACK-1 specifically suppressed transcriptional activation
      derived by NFAT, but not by NF-kappaB. These results demonstrate RACK-1 as a
      potent negative modulator of NFAT activation and suggest a novel mechanism in
      NFAT regulation.

PMID- 12521307
TI  - Regulation of septation and cytokinesis during resumption of cell division
      requires uvi31+, a UV-inducible gene of fission yeast.
AB  - uvi31+ is a sequence homolog of Escherichia coli bolA gene in Schizosaccharomyces
      pombe, identified as a UV-inducible gene. Here, the cellular function of uvi31+
      was investigated by null mutant analysis. Deletion of uvi31+ led to a delayed
      germination of spore and defects in subsequent cell division. However, the uvi31
      mutant cell proliferated faster with smaller cell size than the wild-type cell
      during vegetative growth. In addition, the uvi31 mutant was sensitive to UV
      light. It showed a normal cell cycle delay after UV-irradiation but displayed
      aberrant septum formation and defective cytokinesis when released from the UV
      damage checkpoint. These results suggest that uvi31+ may be involved in control
      of cell division, especially during the resumption from cell cycle arrest.

PMID- 12521308
TI  - Pap1-dependent regulation of the GSTII gene from the fission yeast.
AB  - The genomic DNA encoding a second glutathione S-transferase (GSTII) was
      previously isolated from the fission yeast Schizosaccharomyces pombe. Its
      expression was shown to be induced by menadione, mercuric chloride, o
      dinitrobenzene, and NO-generating S-nitroso-N-acetylpenicillamine using the GSTII
      lacZ fusion harboring the 910 bp upstream region from the translational
      initiation point. In this study, the additional fusion plasmids pGST50-590 and
      pGST50-6R-590 were constructed to carry the 590 bp upstream region in the vectors
      YEp357 and YEp367R, respectively. The synthesis of beta-galactosidase from the
      fusion plasmid pGST50-590 was about 3-fold higher than that from the fusion
      plasmid pGST50-F, indicating the presence of negatively activating sequence in
      the -910 to approximately -590 region. It was also enhanced by the same agents,
      which induced the synthesis of beta-galactosidase from the fusion plasmid pGST50
      F. The synthesis of beta-galactosidase from both fusion plasmids pGST50-F and
      pGST50-590 was enhanced by the overexpressed Pap1 protein. The synthesis of beta
      galactosidase from the two YEp367R derivatives pGST50-6R-F and pGST50-6R-590 was
      greatly decreased in the Pap1-negative strain TP108-3C. These results propose the
      Pap1-dependent regulation of the GSTII gene from the fission yeast.

PMID- 12521309
TI  - Post-transcriptional regulation of ura4+ gene expression by glucose in
      Schizosaccharomyces pombe.
AB  - Glucose-inducible gene expression is a fundamental cellular response for optimal
      cell growth, but identities of glucose-inducible genes and its regulatory
      mechanism remain largely elusive in Schizosaccharomyces pombe. Here we report
      that ura4+, encoding orotidine monophosphate decarboxylase (OMPdecase), shows
      glucose-inducible expression regulated at post-transcriptional level. The ura4+
      mRNA level was rapidly decreased by approximately 50% within 20 min after glucose
      depletion and it was readily recovered upon glucose-readdition within 1 h.
      Glucose at above 2% similarly raised the transcript level of ura4+, while low
      concentration (0.1%) was not effective. Interestingly, control of mRNA turnover
      would be the main regulatory step of the glucose-dependent expression of ura4+.
      Moreover, stress-activated MAPK (SAPK) pathway was partially responsible for the
      glucose-regulated expression of ura4+ and rrg1+, another example of glucose
      dependent mRNA stability control in S. pombe. These results suggest that the SAPK
      pathway might participate in the glucose-dependent regulation of ura4+ and rrg1+
      mRNA stabilities.

PMID- 12521310
TI  - The Pap1-independent induction by metal ions of a third gene encoding glutathione
      S-transferase gene from the fission yeast.
AB  - A third gene that encodes glutathione S-transferase (GSTIII) was previously
      cloned from the fission yeast Schizosaccharomyces pombe. Using the GSTIII-lacZ
      fusion plasmid pGDA-19, its expression was shown to be enhanced by various metal
      ions. In the present study, four additional fusion plasmids, pGDA-29, pGDA-39,
      PGDA-49, and pGDA-59, were designed to carry 998, 378, 276, and 115 bp upstream
      regions from the translational initiation point, respectively. The major
      activation region was located between -998 and -378 bp upstream of the GSTIII
      gene. Regulatory sequences that are responsible for the induction by metal ions
      reside between -998 and -378 bp and between -276 and -115 bp upstream of the
      gene. The overexpressed Pap1 exerts a repression effect on the GSTIII expression
      via -998 to approximately -378 bp region, whereas it exerts an activation effect
      on the GSTIII expression via -270 to approximately -115 bp region. However, the
      induction of the GSTIII gene by metal ions occurs independent of Pap1.

PMID- 12521311
TI  - The effect of head posture on the pharyngeal airway space (PAS).
AB  - The purpose of this study was to investigate the relationship between cranio
      cervical inclination and pharyngeal airway space (PAS) by measuring these
      parameters at different head postures in the same subjects and to obtain a
      regression equation to correct the values measured. Fifty lateral cephalometric
      radiographs taken at five different head postures per individual were obtained
      from ten adults (seven males and three females) aged from 25 to 30 years with
      nose breathers and Class I occlusion. The changes in cranio-cervical inclination
      produced by head extension were correlated with changes in the variables
      describing the PAS. The OPT/NSL (cranio-cervical inclination in the second
      vertebrae) and C3-Me (distance between the third vertebrae and the Menton)
      correlated strongly with PAS-TP (the most proximal distance measured between the
      posterior pharyngeal wall and the tongue base) in the pharyngeal airway space (r
      = 0.807 and 0.854 respectively). The regression equations were Y = - 27.177+0.39X
      (Y = PAS-TP, X = OPT/NSL), and Y = -21.105+0.402X (Y = PAS-TP, X = C3-Me),
      respectively. From these equations we could conclude that an increase of 10
      degrees in OPT/NSL or 10 mm in C3-Me increased the pharyngeal airway space (PAS
      TP) by about 4 mm.

PMID- 12521312
TI  - A modified temporalis transfer in facial reanimation.
AB  - A modified surgical procedure for temporalis transfer in facial reanimation of
      five consecutive cases is presented. Instead of the traditional stripping of the
      temporalis from its origin, its attachment at the coronoid removed, and to its
      end, the harvested fascia lata graft was sutured to lengthen the muscle's action.
      These fibres were then passed to the Orbicularis Oculi and Oris to aid in
      reanimation and to improve their tone. The procedure is less extensive, provides
      a direct line of pull with good functional results, no muscle atropy since
      vascularity and innervation is maintained. No complaints of paresthesia,
      hyposthesia or scar on donor leg was noticed. None of the patients required a
      revision of surgery for unacceptable contour or asymmetry. This simple procedure
      has helped reconstruction of natural symmetrical smile with highly successful
      results.

PMID- 12521313
TI  - The influence of orthodontics on selection and breakage underlying food
      comminution in pre-orthognathic surgery patients.
AB  - Comminution of food is the composite result of selection and breakage. Selection
      is characterized by the chance that a food particle will at least be damaged by
      the teeth during a chew. For any particle size, this chance equals the ratio
      between the weight of damaged and broken particles and that of all initial
      particles. The breakage process refers to fracturing of selected particles. Since
      orthodontic treatment applied to patients before orthognathic surgery has an
      effect on the position and orientation of teeth, it may alter chewing efficiency
      by influencing selection and/or breakage. The effect of such orthodontic
      treatment on chewing efficiency was examined using eight cubes of 8.0 mm of a
      silicone-rubber (Optosil) as a test food for determining the number of chews
      required to halve the initial particle size (N(1/2)) in 12 patients. Three
      particle sizes (2.4, 4.8 and 8.0 mm) were used for determining selection and
      breakage in one-chew experiments. Orthodontic treatment had no effect on the
      chewing efficiency and the selection chances of all particle sizes whereas the
      degree of breakage was significantly (P<0.05) increased only for a particle size
      of 8.0 mm. These findings suggest that presurgical orthodontics has only a minor
      effect on food comminution.

PMID- 12521314
TI  - Magnetic resonance imaging findings of osteoarthrosis and effusion in patients
      with unilateral temporomandibular joint pain.
AB  - The purpose of this study was to investigate the relationship between the
      presence of temporomandibular joint (TMJ) pain and the magnetic resonance (MR)
      imaging findings of osteoarthrosis (OA), and effusion. The study comprised 112
      consecutive TMJ pain patients. Criteria for including a patient were report of
      unilateral pain near the TMJ, with the presence of unilateral TMJ pain during
      palpation, function, and/or unassisted or assisted mandibular opening. Bilateral
      sagittal and coronal MR images were obtained to establish the presence or absence
      of TMJ OA, and/or effusion. Comparison of the TMJ side-related data showed a
      significant relationship between the clinical finding of TMJ pain and the MR
      imaging diagnoses of TMJ OA (P=0.000), and TMJ effusion (P=0.000). Further, there
      was a significant relationship between the MR imaging diagnosis of TMJ OA and TMJ
      effusion (P=0.000). Use of the Kappa statistical test indicated poor diagnostic
      agreement between the presence of TMJ pain and the MR imaging diagnosis of TMJ OA
      (K=0.22), TMJ effusion (K=0.29), and TMJ 'OA and effusion' (K=0.30). The study's
      findings suggest that while clinical pain is correlated to TMJ-related MR imaging
      findings, clinical pain in and of itself, is not reliable for predicting the
      presence of TMJ OA and/or effusion. Validation of MR imaging diagnoses would
      involve the investigation of cross-sectional and longitudinal evidence to assess
      decisive differences in terms of prognosis and/or treatment outcome.

PMID- 12521315
TI  - The evaluation of temporomandibular joint disc position in TMJ disorders using
      MRI.
AB  - The purpose of this study was to correlate disc position and the type of disc
      displacement, intra-capsular effusion and degenerative changes of the condyle as
      demonstrated in MRI studies. In this study, 126 temporomandibular joints (TMJs)
      of 63 patients with TMJ disorders were investigated using clinical examination
      and MRI. One hundred and twelve TMJs were found to have internal derangement as
      disc displacement. The angle between the posterior margin of the disc and the
      vertical line drawn through the centre of the condyle was measured on MRI for
      each TMJ. The positions of the discs were normal, 0 degrees-10 degrees, in
      11.11%; slightly displaced, 11 degrees-30 degrees, in 37.30%; mildly displaced 31
      degrees-50 degrees, in 15.08%; moderately displaced, 51 degrees-80 degrees, in
      7.14% of the TMJs with anterior displacement with reduction (ADDR). The disc
      position was severely displaced anteriorly, as over 80 degrees, in all TMJs with
      anterior disc displacement without reduction (ADD), constituting 27.78% of all
      cases. We found that the smaller the degree of disc displacement the milder the
      internal derangement and that the intra-capsular effusion was more frequently
      associated with TMJ with ADDR. The degenerative condylar changes were more severe
      with an increased degree of anterior disc displacement.

PMID- 12521316
TI  - Neck dissection in oral cancer--clinical review and analysis of prognostic
      factors.
AB  - The purpose of this study was to evaluate the oncologic effectiveness of radical
      and different types of modified neck dissections with preservation of the spinal
      accessory nerve, internal jugular vein and sternocleidomastoid muscle and to
      identify prognostic factors for regional control and survival in univariate and
      multivariate analysis. This retrospective study included 373 patients with
      squamous cell carcinoma of the oral cavity who underwent 401 neck dissections
      between January 1986 and December 1997 at the Department for Oral and
      Maxillofacial Surgery, Hanover Medical School. The actuarial neck control rate
      after 5 years was estimated with 87%. Neck failure occured only within the first
      2 years after neck dissection. The number of positive nodes, macroscopic
      extracapsular spread, peeling off metastases from carotid artery and cranial base
      and preoperative radiochemotherapy were significant prognostic factors. Grade of
      metastases, microscopic extracapsular spread, lymphangiosis carcinomatosa and
      postoperative radiation showed no prognostic significance. The comparison of neck
      failures after radical and modified neck dissection demonstrated a tendency to
      improved regional control after radical neck dissection with increasing extent of
      neck disease.

PMID- 12521317
TI  - Autologous concentrated platelet-rich plasma (cPRP) for local application in bone
      regeneration.
AB  - Platelets are rich in growth factors that may contribute to an accelerated tissue
      regeneration process. The therapeutic osteogenic effect of local platelet
      administration probably depends on the amount of growth factors delivered within.
      To improve platelet-derived factor preparations, the platelets have to be
      concentrated without loss of the granular growth factor load. An autologous
      procedure according to the Good Manufacture Practice (GMP) guidelines to prepare
      a high concentrate from platelet-rich plasma (cPRP) for clinical application in
      bone regeneration is presented. Platelet-rich plasma (PRP) was generated from the
      centrifugation supernatant of 250 ml anticoagulated autologous blood. The PRP was
      then further centrifuged at the day of operation to generate concentrated PRP
      (cPRP) in 8 ml plasma. The data from 34 patients (9 m, 25 f), ageing from 21 to
      71 years (median 50.4) were evaluated. Both, the platelet counts as well as the
      TGF-beta1 concentrations in the cPRP were found to be 12-fold increased compared
      to the PRP values. Overall, a 17-fold increase in platelet concentrations was
      achieved compared to the patients' whole bloods and platelet counts correlated
      with increased levels of TGF-beta1 within the cPRP. These results give rise to
      quality control specifications for a safe and cost effective preparation of cPRP.
      The method has proven to be suitable for blood services to support the needs for
      treatment in oral and maxillofacial surgery.

PMID- 12521318
TI  - Is lingual nerve protection necessary for lower third molar germectomy? A
      prospective study of 300 procedures.
AB  - Lingual nerve damage is one of the most common complications of lower third molar
      removal. However evaluation of the factor involved in these lesions is difficult
      since most previous series are heterogeneous. The purpose of this prospective
      randomized study was to ascertain the impact of lingual nerve protection in a
      homogeneous series including only patients undergoing third molar germectomy
      (i.e. removal of the developmental bud prior to anchoring of the roots in the
      jaw). Data from a total of 300 germectomy procedures were included in this study.
      All procedures were performed by the same experienced surgeon randomly with or
      without lingual nerve protection. No lingual nerve injury was observed after
      third molar germectomy regardless of whether or not lingual nerve protection was
      used. Lingual nerve protection is unnecessary for lower third molar germectomy.

PMID- 12521319
TI  - Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy.
AB  - We selected two homogenous groups, each of 22 patients with idiopathic dysgeusia,
      an altered perception of taste, matched for age and sex, for an open trial of
      alpha lipoic acid compared with placebo. The 22 patients in the study group were
      treated with alpha lipoic acid for 2 months. The 22 patients in the control group
      were treated for 2 months with carboxymethylcellulose. The latter group was then
      treated with alpha lipoic acid for 2 months. The results showed significant
      symptomatic improvements compared with placebo, in both groups of patients with
      dysgeusia treated with alpha lipoic acid, suggesting that idiopathic dysgeusia
      may be a neuropathy comparable to the burning mouth syndrome.

PMID- 12521320
TI  - Oral surgical management of patients with mechanical circulatory support.
AB  - After the introduction of mechanical circulatory support (MCS) for treatment of
      patients with severe cardiogenic shock, the survival rate of these patients
      increased significantly. Temporary MCS may be applied over a period of several
      days up to months prior to heart transplantation (HTx). Oral surgical management
      of patients with MCS is seriously complicated by a combination of anticoagulant
      and antiaggregant medication. Moreover, contact of blood with artificial
      surfaces, i.e. polyurethane and silicone, may increase the risk of thromboembolic
      events and infections. A total of 32 patients with MCS (29 men and three women
      with a median age 48 years [range 27-60 years]) were examined for odontogenic
      foci, treatment needs and local and cardiovascular complications after oral
      surgical intervention. In 27 patients (84%) at least one potential focus was
      diagnosed. Following tooth extraction 4 out of 6 patients presented with local
      haemorrhage (n=3) and thromboembolic events (n=2). Generally MCS has to be
      considered a relative contraindication for elective oral surgical interventions.

PMID- 12521321
TI  - Complications in HIV-infected and non-HIV-infected haemophiliacs and other
      patients after oral surgery.
AB  - Dental extractions and other oral surgical procedures, including local analgesic
      injections, potentially can cause problems in haemophiliac and HIV infected
      persons. There are few data on treatment results in HIV-infected haemophiliacs
      compared with non-HIV-infected haemophiliacs. The oral surgery treatment results
      in 48 patients with special needs, including HIV-infected haemophiliacs, non-HIV
      infected haemophiliacs, HIV-infected non-haemophiliacs, and a group with other
      medical problems were therefore studied. Around 20% of the haemophiliacs
      developed post-oral surgical complications, which was not significantly different
      whether or not they were HIV-infected. However, complications were less frequent
      (8%) in HIV-infected non-haemophiliacs or other patients with special needs.
      Although the patient groups are not large, it would appear that haemophiliacs had
      more postoperative complications but that the presence of HIV infection had no
      notable influence on treatment outcome.

PMID- 12521322
TI  - Early bone healing events in the human extraction socket.
AB  - The tooth extraction socket is unique in terms of a bone-healing defect in that
      it contains the remnants of periodontal ligament fibroblasts attached to the
      socket wall. Although these cells have an osteogenic potential in vitro, the
      origin of cells populating the human extraction socket is unknown and may include
      bone marrow, periosteum and pericytic cells. Recently, monoclonal antibodies (AML
      3, SB-10 and SB-20) have become available which can identify cells undergoing
      osteogenic differentiation. The aim of this work was to investigate the pattern
      of osteoblast differentiation in the human extraction socket using these markers.
      Immunolocalization was used to identify the osteoprogenitor cell population in
      the extraction sockets of three patients. Runx2 was most strongly expressed by
      the osteoblasts at the socket margin and in the surrounding marrow spaces.
      Osteoprogenitor, pre-osteoblast and osteoblast cells surrounded the newly formed
      trabeculae, and expressed on their cell surface antigens which reacted with the
      SB-10 and SB-20 antibodies. In a specimen with the tooth and periodontium
      present, both osteo-blasts and periodontal ligament fibroblasts were
      immunoreactive with SB-10, and SB-20 and also expressed Runx2. There was
      heterogeneity of expression of these osteogenic markers e.g. not all osteoblasts
      expressed Runx2. We have shown that osteoprogenitor cells in the residual
      periodontal ligament and bone marrow may contribute to bone regeneration
      following tooth extraction.

PMID- 12521323
TI  - Temporomandibular joint synovial fluid sampling: estimation of dilution factor
      using calcium ion concentration.
AB  - Saline aspirates have been commonly used in the biochemical investigations of
      temporomandibular joint (TMJ) pathology. However, due to presence of adhesions in
      the diseased temporomandibular joint, full equilibration between the injected
      saline and the synovial fluid may not be achieved in all cases. We measured
      calcium ion concentration in the saline aspirates and the plasma to assess the
      degree of dilution of the synovial fluid by the injected media. Saline aspirates
      obtained prior to the arthroscopic examination of 17 patients with painful TMJs
      not responding to 3 months of conservative treatment were analysed for their
      calcium content by a highly sensitive spectrophotometric autoanalyser. In 10
      patients with unilateral symptoms, the contralateral asymptomatic side was used
      as a control. Using a concentration volume equation the amount of the synovial
      fluid in the saline aspirates was calculated. The yield of the saline aspirates
      was variable ranging from 330 to 1000 microl. The mean calcium level was 0.787
      mg/dl in the symptomatic group (C.I. 95% 0.337-1.237 mg/dl) and 0.512 mg/dl (C.I.
      95% 0.235-0.797) in the asymptomatic group. Using a Student t-test there was no
      significant difference between the two groups. Furthermore, there was no
      demonstrable correlation between the volume of the aspirate and its synovial
      fluid content. This study confirms that the saline aspirate may not be a
      representative sample of the TMJ synovial fluid, and that expression of the
      results of the biochemical assays per volume of the aspirate may be misleading.

PMID- 12521324
TI  - The biological behaviour of human adenoid cystic carcinoma cells transduced with
      interleukin-2-gene.
AB  - Adenoid cystic carcinoma (ACC) of the salivary glands is a highly infiltrative
      malignant tumour with a tendency for lung metastasis. Gene therapy could be a
      potentially effective therapy for ACC and its metastasis. The aims of the study
      were: To transduce interleukin-2 (IL-2) gene into an ACC cell line with
      predisposition for lung metastasis (ACC-M); to compare the bioactivity of the
      gene-transduced cells and the parent cell line in vitro and in vivo. The IL-2
      gene was transduced via a bicistronic retroviral vector into the ACC-M cells. The
      growth rate and DNA cell cycles of the parent ACC-M, the control viral vector
      AmGCEN, and the gene transduced AmIL-2 cell cultures were compared quantitatively
      and by flow cytometry, respectively. The tumourigenic ability of the three cell
      lines was verified by inoculation in athymic nude mice. The tumours developed
      were extracted and compared quantitatively and histologically. There was no
      difference in the growth rate and the DNA count between the ACC-M, AmGCEN, and
      AmIL-2 cell cultures. In the animal experiment, both the ACC-M and AmGCEN cells
      stimulated lung metastasis in all the mice, whereas there was no tumour found in
      the 1 x 10(6) AmIL-2 cells inoculation. On 3 x 10(6) AmIL-2 cells stimulation,
      three out of six mice developed tumours but the mass and volume of the tumours
      were smaller than the other two groups. Under light microscopy, the ACC-M tumours
      were mainly poorly differentiated with minimal cellular matrix, whereas the AmIL
      2 tumours were well differentiated with ample matrix. The transduction of IL-2
      gene can reduce the tumourigenicity of ACC-M cells and induces tumour cell
      differentiation in mice. The IL-2 gene can be a potential effective gene for the
      treatment of adenoid cystic carcinoma of salivary glands and its lung metastasis.

PMID- 12521325
TI  - Alcohol-related violence and the role of oral and maxillofacial surgeons in multi
      agency prevention.
AB  - The maxillofacial region is by far the most frequently selected target in
      assaults on adults. There is a causal link between alcohol intoxication and
      injury. Therefore, oral and maxillofacial surgery is, in effect, the lead
      speciality for those injured in violence and has a responsibility to orchestrate
      holistic care that takes into account mental health needs. Recent years have also
      seen a determined effort by oral and maxillofacial surgeons to get involved in
      wider issues of prevention, exemplified by the national UK BAOMS Facial Injuries
      Awareness Week. Multi-agency prevention, not just with mental health
      professionals in the case of individual patients, but also with emergency
      medicine, public health, local government, the police and the voluntary sector is
      key to success. Given the potential complexity of collaborations like this, it is
      important to understand what works in multi-agency prevention. This paper reviews
      successful interventions: their rationale and how oral and maxillofacial surgeons
      can contribute to local injury prevention.

PMID- 12521326
TI  - Quality of life 2-10 years after combined treatment for advanced oral and
      oropharyngeal cancer.
AB  - This study reports the findings of an evaluation of Quality of Life (QOL) in long
      term survivors of advanced oral and oropharyngeal cancer treated with
      preoperative chemoradiotherapy followed by surgery (combined treatment=multimodal
      therapy). All patients had T2-T4 tumours and all received locoregional radical
      resection and simultaneous microvascular reconstruction. From 1990 to 1998, 181
      patients have been treated at the University Hospital of Cranio-Maxillofacial and
      Oral Surgery in Vienna. 100 (55%) of these patients were alive and free of
      disease in 2000. Sixty-seven of them completed the EORTC questionnaires QLQ 30
      and QLQ H&N 35. We found these questionnaires to be very good tools for
      determining QOL, which constitutes part of the therapeutic success. Patients
      tended to report good to very good QOL. A comparison between groups according to
      clinical data was conducted as well as a group comparison of patients who claimed
      especially high or low QOL in the questionnaires. It was found that combined
      treatment not only offers the best chances for survival, but also allows a
      subsequent QOL, that is comparable to other forms of therapy.

PMID- 12521327
TI  - Patient-centred outcome measures in oral medicine: are they valid and reliable?
AB  - The present study evaluates the performance of patient-centred outcome measures
      in the oral medicine setting in patients with oral lichen planus. The study
      included 48 patients with a histologically confirmed diagnosis of oral lichen
      planus who completed a questionnaire incorporating two patient-centred outcome
      measures: the 16-item UK Oral Health Related Quality Of Life Measure (OHQOL-UK)
      and 14-item Oral Health Impact Profile (OHIP-14). They subsequently underwent an
      oral examination and rated the pain they experienced on a visual analogue scale
      (VAS). The impact of oral health on their life quality was considerable with
      physical, social and psychological consequences. Both OHQOL-UK (P<0.01) and OHIP
      14 scores (P<0.01) were associated with clinical findings; demonstrating
      criterion validity. Patient rating of pain experienced (on a VAS) correlated with
      OHQOL-UK scores (P<0.01) and OHIP-14 (P<0.01); demonstrating construct validity.
      The mean inter-item correlation for OHQOL-UK was 0.93 and was 0.90 for OHIP-14;
      demonstrating high internal consistency reliability. Our results suggest both
      OHQOL-UK and OHIP-14, patient-centred outcome measures perform well in patients
      with oral lichen planus, demonstrating validity and reliability. This implies
      patient-centred outcome measures may be utilized in both oral medicine and oral
      and maxillofacial surgery to assess patient needs and opinions.

PMID- 12521328
TI  - Transport distraction osteogenesis following marginal resection of the mandible.
AB  - We performed sliding transport distraction osteogenesis (STDO) of an alveolar
      segment containing an unerupted third molar in the mandible of a 22-year-old man
      with a benign cementoblastoma. Marginal mandibulectomy including the tumour and
      the right mandibular second premolar and first and second molars was done. STDO
      was performed to horizontally reconstruct the alveolar ridge and to restore
      occlusion with the use of the third molar. After forward horizontal distraction
      of the alveolar segment, the third molar spontaneously erupted and was gradually
      moved to the position previously occupied by the second molar.

PMID- 12521329
TI  - Repair of oroantral communications in the third molar region by random palatal
      flap.
AB  - Various palatal flap procedures based on the greater palatine vessels have been
      advocated for the repair of oroantral communications (OACs). However, when the
      defect is located in the third molar region, difficulty is encountered in using
      the palatal flap because rotation is hindered by the vascular pedicle. In this
      study, we used random palatal flaps to repair OACs in the third molar area in 21
      patients. The vascular pedicles were ligated and severed in all cases in order to
      evaluate whether it was necessary to preserve the greater palatine vessels when
      using the palatal rotation flap (PRF). The repair was successful in 16 cases
      (76.2%). The length/width ratio of the flap was the most important factor
      determining the outcome. The ratios were 2.23 +/- 0.12 and 2.40 +/- 0.14 in the
      success and failure groups, respectively and their difference was statistically
      significant (P<0.05). Other clinical parameters such as age, gender, antral
      infection, tooth displacement into the sinus and duration of the communication
      had no influence on the outcome (P>0.05). The study showed that the PRF with the
      appropriate length/width ratio can safely be used in a random fashion. This
      provided another option in the repair of oroantral communications of difficult
      locations such as in the tuberosity area.

PMID- 12521330
TI  - Solitary fibrous tumour of the tongue: a case report with immunohistochemical
      studies.
AB  - The solitary fibrous tumour (SFT), also known as a localized fibrous
      mesothelioma, is a neoplasm characterized by the proliferation of capillaries
      surrounded by masses of round or spindle-shaped cells. SFT has been discovered in
      many locations, however, it is extremely rare for SFT to be found in the
      intraoral region. We report here case of SFT arising from the tongue of a 75-year
      old woman. To our knowledge, this is the second case reported of SFT originating
      from the tongue.

PMID- 12521331
TI  - A recurrent case of odontogenic ghost cell tumour of the mandible.
AB  - Odontogenic ghost cell tumour (OGCT), also referred to as dentinogenic ghost cell
      tumour, is an extremely rare tumour classified as a neoplastic variant of
      calcifying ondontogenic cyst (COC). To date, only 13 cases of OGCT arising in the
      maxilla or mandible have been reported. We describe an OGCT that recurred after
      segmental resection of the mandible in a 59-year-old man. Histopathological
      examination revealed tumour invasion of the surrounding cortical bone, areas
      containing numerous calcifying flaky cell nests, and dentinoid matrix near
      epithelial cell nests. No atypical mitosis was found. There has been no evidence
      of recurrence or metastasis in the 4 years after operation.

PMID- 12521332
TI  - Fatal necrotizing stomatitis due to Trichoderma longibrachiatum in a neutropenic
      patient with malignant lymphoma: a case report.
AB  - Primary invasive mold infection of the oral cavity is a rare but serious
      complication in immunocompromised hosts. We report a case of fatal Trichoderma
      longibrachiatum stomatitis in a 66-year-old female patient with malignant
      lymphoma. The infection rapidly disseminated from the oral mucosa to the lungs
      during neutropenia. Despite intensive antifungal therapy with amphotericin B and
      itraconazole, there was a fatal progression of the condition. While Trichoderma
      species have been recognized to be pathogenic in profoundly immunosuppressed
      hosts, this is the first report of the primary oral focus causing a fatal
      infection.

PMID- 12521333
TI  - Noninvasive assessment of cardiac resynchronization therapy for congestive heart
      failure using myocardial strain and left ventricular peak power as parameters of
      myocardial synchrony and function.
AB  - INTRODUCTION: Although invasive studies have shown that cardiac resynchronization
      therapy by biventricular pacing improves left ventricular (LV) function in
      selected heart failure patients, it is impractical to apply such techniques in
      the clinical setting. The aim of this study was to assess the acute effects of
      cardiac resynchronization therapy by noninvasive techniques. METHODS AND RESULTS:
      Twenty-two patients enrolled in the InSync trial (age 64 +/- 9 years, 18 men and
      4 women; all with ejection fraction < 35% and QRS > 130 msec) were studied 1 to
      12 months after pacemaker implantation during pacing, and while ventricular
      pacing was inhibited. Regional myocardial strains of the interventricular septum,
      LV free wall, and right ventricular free wall were derived from color Doppler
      tissue echocardiography. Peak power index was calculated as a product of
      simultaneously recorded noninvasive blood pressure and pulse-wave (PW) Doppler
      velocity of the LV outflow tract. The Z ratio (sum of LV ejection and filling
      times divided by RR interval) and tei index were calculated from PW Doppler data.
      During pacing, overall regional strain improved (P = 0.01), while the LV strain
      coefficient of variation decreased from 2.7 +/- 2.4 to 1.3 +/- 0.7 (P = 0.009).
      Additionally, peak power index improved from 84 +/- 24 to 94 +/- 27 cm x mmHg/sec
      (P = 0.004). The Z ratio increased from 0.71 +/- 0.08 to 0.78 +/- 0.07 (P =
      0.0005), while the tei index decreased from 0.86 +/- 0.33 to 0.59 +/- 0.16 (P =
      0.0002). CONCLUSION: Using novel noninvasive indices, we demonstrated that
      cardiac resynchronization therapy improves LV performance.

PMID- 12521334
TI  - The strain of resynchronizing the failing heart.

PMID- 12521335
TI  - Linearly scaled, rate-invariant normal limits for QT interval: eight decades of
      incorrect application of power functions.
AB  - INTRODUCTION: Normal limits for QT traditionally are derived as mean +/- 2*SD,
      with rate adjustment done by dividing QT values by power functions such as RR 1/2
      (proportional scaling). METHODS AND RESULTS: We evaluated procedures for deriving
      normal limits by comparing adjusted QT distributions versus heart rate using ECG
      data of 11,739 normal men and women aged > or = 40 years. QT decreased as
      predicted by many power functions with heart rate but its SD remained relatively
      unchanged. Consequently, proportional scaling induced rate-dependent distortion
      of normal limits. Furthermore, QT distributions by heart rate were variably
      skewed and non-normal. Therefore, normal limits expressed as mean +/- 2*SD were
      misleading. Omission of regression intercept was an additional reason for failure
      of Bazett's and Fridericia's formulas. Regularized normal limits for adjusted QT
      (Qta) were obtained with linear instead of proportional scaling of type QTa = QT
      + k1*(1 - RR(k2)), for instance, with k2 = 0.5, k1 = 0.360 for males and 0.353
      for females, or with k2 = 0.42, k1 = 0.414 for males and 0.420 for females. With
      linear scaling, QTa = 460 msec was established as the upper 2% normal limit, with
      32 msec as the limit for a significant QTa increase from reference ECG in serial
      comparison. CONCLUSION: Traditional procedures for establishment of normal limits
      failed because of proportional scaling, assumption of normal QT distribution, or
      omission of regression intercept. Percentile distributions of linearly scaled
      adjusted QT produced regularized rate invariant normal limits within normal sinus
      rates.

PMID- 12521336
TI  - Is there a physiologic QT/RR relationship?

PMID- 12521337
TI  - Accessory pathway localization by QRS polarity in children with Wolff-Parkinson
      White syndrome.
AB  - INTRODUCTIONS: Location of the accessory pathway (AP) in Wolff-Parkinson-White
      (WPW) syndrome can be determined accurately by the QRS polarity on resting ECG.
      These ECG characteristics may be different in children, and no algorithm has yet
      been tested. METHODS AND RESULTS: A total of 153 resting ECGs of symptomatic
      children with WPW syndrome were retrospectively analyzed. The anatomic AP
      location had been established fluoroscopically at eight possible sites during
      radiofrequency catheter ablation. Two independent observers predicted AP location
      on blinded ECGs with a QRS polarity algorithm for adults using leads II, III,
      aVL, V1, and V2. Subsequently, the QRS polarity for all individual ECG leads was
      evaluated and a new algorithm for children was devised. With the adult algorithm,
      the observers correctly predicted only 55% to 58% of AP locations. The septal and
      right-sided pathways often were inseparable, and mid-septal and parahisian
      pathways were missed. In the new children's algorithm, left lateral, left
      posteroseptal, and posteroseptal pathways shared a positive or intermediate QRS
      polarity on V1, with the left lateral pathway separated by a positive QRS
      polarity on lead III. Negative QRS polarity on lead V1 and positive QRS polarity
      on lead V3 were shared by right posteroseptal, mid-septal, parahisian, and
      anteroseptal pathways, with the latter two having a positive QRS polarity on lead
      aVF. Right lateral pathways had negative QRS polarity on lead V1 and negative or
      intermediate QRS polarity on lead V3. Overall accuracy for these five regions was
      90%. CONCLUSION: AP characterization by QRS polarity in children with WPW
      syndrome is more diverse than in adults and requires other ECG leads to establish
      five AP regions.

PMID- 12521338
TI  - Postinfarction risk assessment for sudden cardiac death using late potential
      analysis of the digital Holter electrocardiogram.
AB  - INTRODUCTION: Noninvasive postinfarction risk assessment for sudden cardiac death
      is limited. Standard analysis of the signal-averaged QRS complex can identify
      patients at risk for monomorphic ventricular tachycardia, but its value for
      discriminating patients at risk for sudden death is low. METHODS AND RESULTS: The
      aim of this study was to prospectively investigate repeated late potential
      analysis of digital Holter ECG and compare it with standard analysis of the
      signal-averaged QRS complex within a short ECG period and with common clinical
      risk factors for sudden cardiac death in 756 consecutive patients after acute
      myocardial infarction. Digital Holter ECG were subdivided into 5-minute segments,
      and late potential analysis was performed on each 5-minute segment. During follow
      up of 32 +/- 15 months, 35 patients died of sudden cardiac death and 50 patients
      died of nonsudden cardiac death. Sudden cardiac death was associated with
      ejection fraction < 40%, nonsustained ventricular tachycardia, creatine kinase >
      1,000 IU/L, and late potentials in > 75% of analyzed Holter ECGs (abnormal LP75),
      but not with late potentials determined by only a short ECG period. According to
      multivariate analysis, the best independent significant predictor of sudden
      cardiac death was abnormal LP75 (P = 0.002, sensitivity 29%, specificity 96%,
      positive predictive value 40%, negative predictive value 97%). Nonsudden cardiac
      death was associated with ejection fraction < 40% (P = 0.001). CONCLUSIONS: Late
      potential analysis of digital Holter ECG is a powerful tool that can be used to
      determine postinfarction patients at risk for sudden cardiac death and is
      optimized when combined with determination of ejection fraction.

PMID- 12521339
TI  - Bundle branch reentrant tachycardia in patients with apparent normal His-Purkinje
      conduction: the role of functional conduction impairment.
AB  - INTRODUCTION: His-Purkinje conduction delay, manifested by bundle branch block
      QRS complex configuration or by HV interval prolongation, is considered an
      essential condition for maintenance of bundle branch reentrant tachycardia
      (BBRT). METHODS AND RESULTS: Of 178 patients with different types of ventricular
      tachycardia (VT), 13 were found to have BBRT as the underlying electrophysiologic
      mechanism. Of these 13 patients (9 men and 4 women; mean age 64 +/- 13 years), 6
      had an HV interval < or = 55 msec (group A), and 7 had a prolonged HV interval (>
      55 msec; group B) during sinus rhythm (SR). PR interval (169 +/- 32 vs 339 +/-
      138 msec, P = 0.01) and QRS duration (116 +/- 17 vs 167 +/- 29 msec, P = 0.003)
      during SR were significantly shorter in group A than in group B. In group A, the
      HV interval was significantly longer during VT than during SR (73 +/- 18 vs 47 +/
      7 msec, P = 0.007). There were more patients with functional His-Purkinje block
      (split His potentials, a jump of HV interval induced by programmed atrial
      stimulation or burst pacing) or phase 3 block in group A than group B (6/6
      patients vs 0/7 patients, P < 0.001). Successful ablation of the right bundle
      branch was performed in all 13 patients without deteriorating AV block. Two
      patients died in each group, and VTs (other than BBRT) or ventricular
      fibrillation were documented by ICD electrogram storages in 4 patients during
      follow-up of 27 +/- 17 months. CONCLUSION: A prolonged HV interval during SR is
      not a prerequisite for BBRT. Functional His-Purkinje system abnormalities appear
      to be the electrophysiologic substrate for this specific type of BBRT.

PMID- 12521340
TI  - Global P wave duration on the 65-lead ECG: single-site and dual-site pacing in
      the structurally normal human atrium.
AB  - INTRODUCTION: Pacing is believed to prevent atrial fibrillation by reducing
      atrial activation time. Exact correlation between P wave duration (PWD) on
      surface ECG and endocardial atrial activation time is still unexplored. METHODS
      AND RESULTS: In 15 patients without structural heart disease (9 women, age 45 +/-
      14 years), single site [high right atrium (HRA), coronary sinus ostium (CSos),
      distal CS (CSd), high RA septum (Bachmann's bundle, BB)] and dual-site pacing
      (various combinations) was performed after ablation of supraventricular
      tachycardia. A 65-lead surface ECG was recorded simultaneously. Endocardial
      atrial activation time was measured off-line (stimulus - last bipolar recording),
      and the respective PWD was assessed using the root mean square and 65-channel
      summary plots. PWD during pacing from BB was significantly shorter (96 +/- 12
      msec) than during HRA (121 +/- 15 msec), CSos (108 +/- 9 msec), and CSd pacing
      (126 +/- 14 msec; P < 0,01, respectively). PWD during dual-site pacing (HRA+BB,
      91 +/- 14 msec; HRA+CSos, 96 +/- 7 msec; HRA+CSd, 90 +/- 7 msec; BB+CSd, 96 +/-
      12 msec) was not significantly shorter than during pacing from BB. Correlation
      between endocardial atrial activation time and PWD was 0.83. CONCLUSION: PWD
      during single-site and dual-site atrial pacing represents endocardial atrial
      activation time and can be measured precisely using the 65-lead surface ECG. The
      fact that high septal pacing results in the shortest PWD may have implications
      for preventive pacing in patients with atrial fibrillation.

PMID- 12521341
TI  - Microelectrode study of the genesis of the monophasic action potential by contact
      electrode technique.
AB  - INTRODUCTION: Despite widespread use of the contact electrode for recording
      monophasic action potentials (MAPs) in both clinical and experimental research,
      the mechanism underlying the genesis of the contact MAP remains unproven. The
      "Franz hypothesis" assumes that the MAP is driven by a current source originating
      at the boundary between cells depolarized by the MAP electrode pressure and
      normal cells immediately adjacent to it. To date, no direct experimental data
      exist to support this hypothesis. METHODS AND RESULTS: In 10 Langendorff-perfused
      mouse hearts, a miniaturized MAP probe was inserted into the right ventricle (RV)
      and gently pressed against the endocardium of the upward-facing RV free wall.
      During stable contact and stable MAP recording, KCl-filled glass microelectrodes
      were lowered from above the RV to record transmembrane action potentials (TAPs)
      at the center of and 0.05 and 0.2 mm outside the perimeter of the MAP electrode
      contact site. TAPs at the center had normal resting potentials (RP) in epicardial
      layers (-78 +/- 4 mV) but showed gradual decrease toward deeper layers, reaching
      a minimum RP of -23 +/- 0.8 mV directly above the MAP electrode surface. RPs at
      0.05 mm outside the MAP perimeter were normal at the epicardial surface and with
      increasing transmural depth showed significantly less decrease than central
      recordings (min RP -41 +/- 0.8 mV, n = 11, P < 0.00001). TAPs at 0.2 mm from the
      MAP electrode perimeter had normal RPs across the entire RV wall. CONCLUSION:
      These direct data are the first to support the hypothesis that the MAP is
      generated locally through pressure depolarization of a circumscript volume of
      cells that (1) has sharp voltage gradients toward normal cells, (2) provides a
      strong local current source, and (3) when simulated with a circuit model creates
      the field potential recorded by the contact MAP electrode.

PMID- 12521342
TI  - Termination of reentry by a long-lasting AC shock in a slice of canine heart: a
      computational study.
AB  - INTRODUCTION: A heart in fibrillation can be entrained by long-lasting
      alternating current (AC) stimuli, leading to defibrillation. To investigate the
      role entrainment plays in defibrillation, computer simulations of AC
      cardioversion in a three-dimensional slice of the canine heart were performed.
      METHODS AND RESULTS: A bidomain finite element model of a 1-mm thick slice across
      the ventricles of a canine heart was used to simulate termination of transmural
      reentry with AC shocks. Cardioversion defibrillation thresholds (DFTs) were
      determined for 200-msec (L) AC shocks at varying frequencies. At the DFT, the
      entire tissue is entrained by the AC shock. DFT decreases as the frequency of the
      long-lasting AC shock increases. We hypothesize that this decrease is due to the
      short period of the high-frequency AC waveform, leaving strong virtual electrode
      polarization (VEP) after the shock ends. To test this hypothesis, the end-shock
      VEP were compared for different frequencies, demonstrating stronger polarization
      as frequency increased. To examine whether entrainment by the long-lasting AC
      shock contributes to the VEP at the end of the shock, additional simulations were
      conducted using single-period (Z) AC waveforms. Z waveform DFTs were higher than
      L waveform DFTs; the Z waveform VEP was weaker than the L waveform VEP at the
      same frequency. This indicates that entrainment contributes to the development of
      stronger VEP and, thus, to lower DFT at high frequencies. CONCLUSION: This study
      offers for the first time a mechanistic insight into cardioversion with long
      lasting AC shocks.

PMID- 12521343
TI  - Critique of a computer model study of AC defibrillation.

PMID- 12521344
TI  - Is there an optimal pacing site to prevent atrial fibrillation?: an experimental
      study in the chronically instrumented goat.
AB  - INTRODUCTION: Atrial pacing can reduce the number of recurrences of atrial
      fibrillation (AF). It is unclear the extent to which this effect is determined by
      the site(s) of pacing. METHODS AND RESULTS: In six electrically remodeled goats
      (24-hour AF), the window of inducibility of AF was determined by applying
      premature stimuli (S1-S2) at the right (RA) or left (LA) atrium (baseline
      values). Determination of the window of inducibility of AF at RA and LA was
      repeated during preventive pacing at four sites: RA, LA, Bachmann's bundle (BB),
      and RA+LA (biatrial). Mapping was used to elucidate the mechanisms of prevention
      of AF. At baseline, the window of inducibility of AF was 49 +/- 9 msec at RA and
      45 +/- 17 msec at LA. Initiation of AF was associated with conduction block of
      the premature beat at BB. Preventive pacing at BB markedly shortened the window
      of inducibility of AF at RA (25 +/- 11 msec) and LA (17 +/- 8 msec, P < 0.01).
      Pacing at RA only shortened the window of inducibility of AF at LA (23 +/- 9
      msec, P < 0.01), whereas pacing at LA only shortened the window of inducibility
      of AF at RA (23 +/- 11 msec, P < 0.01). Biatrial pacing failed to shorten the
      window of inducibility of AF both at RA and LA. Prevention of AF by pacing was
      due to prolongation of the premature interval at BB. CONCLUSION: In the caprine
      model of AF, BB is a critical area of conduction of premature beats and
      initiation of AF. Pacing at BB can prevent but not completely abolish the
      initiation of AF by single premature beats (shortening of the window of
      inducibility). Prevention of AF by pacing is based on prolongation of the
      premature interval at BB, thus preventing conduction block and reentry. In
      general, the optimal site for preventive pacing is close to the area of block and
      remote from the origin of premature beats.

PMID- 12521345
TI  - Partial vagal denervation increases vulnerability to vagally induced atrial
      fibrillation.
AB  - INTRODUCTION: Cervical vagal stimulation shortens the atrial effective refractory
      period (ERP) primarily in the high right atrium (HRA) and facilitates induction
      of atrial fibrillation (AF) by single premature HRA extrastimuli. We hypothesized
      that vagal denervation of the HRA prevents both ERP shortening in the HRA and AF
      induction during vagal stimulation. METHODS AND RESULTS: Vagal denervation of the
      HRA was achieved using radiofrequency catheter ablation (RFA) of the fat pad at
      the right pulmonary vein-atrial junction (RPV fat pad). Programmed stimulation
      was performed at each of four atrial sites to measure ERP and inducibility of AF
      during vagal stimulation. RPV fat pad RFA increased only the HRA ERP during vagal
      stimulation (70 +/- 8.7 vs 117 +/-14.8, P < 0.05). RPV fat pad RFA increased
      measures of dispersion of refractoriness, the standard deviation of ERP (24 +/-
      2.1 vs 33 +/- 2.0, P < 0.01), and the standard deviation of AF cycle length (11
      +/- 0.8 vs 22 +/- 1.7, P < 0.001) during vagal stimulation. RPV fat pad RFA
      increased the incidence of AF (15/28 vs 24/28, P < 0.05) and the vulnerability
      (22 +/- 4.7 vs 39 +/- 5.6, P < 0.01) to AF induction during vagal stimulation,
      particularly from left atrial premature beats. After RPV fat pad RFA, premature
      beats induced AF by causing conduction block primarily in the HRA and
      macroreentrant activation around the block. CONCLUSION: Partial right atrial
      vagal denervation facilitated rather than prevented initiation of vagally
      mediated AF.

PMID- 12521346
TI  - Vagal stimulation and atrial fibrillation: experimental models and clinical
      uncertainties.

PMID- 12521347
TI  - Demonstration of electrical and anatomic connections between Marshall bundles and
      left atrium in dogs: implications on the generation of P waves on surface
      electrocardiogram.
AB  - INTRODUCTION: The muscle bundles within the ligament of Marshall (LOM) are
      electrically active. The importance of these muscle bundles (Marshall bundle
      [MB]) to atrial activation and the generation of the ECG P wave is unclear.
      METHODS AND RESULTS: We used optical mapping techniques to study epicardial
      activation patterns in isolated perfused left atrium in four dogs. In another
      seven dogs, P waves were studied before and after in vivo radiofrequency (RF)
      ablation of the connection between coronary sinus (CS) and the LOM. Computerized
      mapping was performed before and after RF ablation. Optical mapping studies
      showed that CS pacing resulted in broad wavefronts propagating from the middle
      and distal LOM directly to the adjacent left atrium (LA). Serial sections showed
      direct connection between MB and LA near the orifice of the left superior
      pulmonary vein in two dogs. In vivo studies showed that MB potentials were
      recorded in three dogs. After ablation, the duration of P waves remained
      unchanged. In the other four dogs, MB potentials were not recorded. Computerized
      mapping showed that LA wavefronts propagated to the MB region via LA-MB
      connection and then excited the CS. After ablation, the activation of CS muscle
      sleeves is delayed, and P wave duration increased from 65.3 +/- 14.9 msec to 70.5
      +/- 17.2 msec (P = 0.025). CONCLUSION: In about half of the normal dogs, MB
      provides an electrical conduit between LA free wall and CS. Severing MB alters
      the atrial activation and lengthens the P wave. MB contributes to generation of
      the P wave on surface ECG.

PMID- 12521348
TI  - Initiation of atrial fibrillation by ectopic beats originating from the ostium of
      the inferior vena cava.
AB  - Ectopic beats triggering atrial fibrillation may arise from atrial myocardial
      extensions in the pulmonary veins, superior vena cava, coronary sinus, and vein
      of Marshall. We report two patients with paroxysmal atrial fibrillation initiated
      by ectopic beats originating from the inferior vena cava. The foci responsible
      for the ectopic beats were located and ablated, resulting in elimination of
      atrial fibrillation. Ectopic beats originating from the os of the inferior vena
      cava can result in atrial fibrillation. This finding may explain the recurrence
      of atrial fibrillation in some patients after pulmonary vein isolation.

PMID- 12521349
TI  - Ventricular fibrillation: ablation of a trigger?
AB  - We report the case of a patient with recurrent ventricular fibrillation (VF) and
      no evidence of structural heart disease. VF was consistently initiated by a
      relatively early-coupled premature ventricular contraction with identical
      morphology on each occasion. Treatment with antiarrhythmic agents failed to
      suppress the arrhythmia. Electrophysiologic testing showed high-frequency
      potential at the earliest activation site, and radiofrequency ablation resulted
      in abolition of the ventricular ectopy with no further VF recurrence. Suppression
      of VF arising from focal triggers in patients with frequent ventricular ectopy
      and normal heart can be achieved with catheter ablation, but further studies are
      needed to evaluate the prevalence of such a mechanism.

PMID- 12521350
TI  - Pulmonary vein firing triggering atrial fibrillation after open heart surgery.
AB  - We report the case of a 44-year-old woman with obstructive hypertrophic
      cardiomyopathy without history of prior arrhythmias who underwent surgical
      myectomy. She developed symptomatic postoperative atrial fibrillation (AF) that
      was refractory to antiarrhythmic therapy and could not be adequately rate
      controlled. AF always was preceded by short and fast runs of atrial tachycardia.
      In the electrophysiology laboratory, this arrhythmia appeared to originate from
      the right superior pulmonary vein and conducted with variable degrees of exit
      block. Pulmonary vein isolation guided by circular mapping was performed, and no
      further episodes of either atrial tachycardia or AF were noted. This case
      highlights the potential role of the pulmonary veins in the pathophysiology of
      postoperative AF.

PMID- 12521351
TI  - Are we lost in the labyrinth of the sinoatrial node pacemaker mechanism?
AB  - Despite extensive electrophysiologic studies performed to date, the ionic
      mechanisms of sinoatrial node pacemaker activity are unclear. This article
      highlights three recent topics associated with this issue: (1) sustained inward
      current (Ist)); (2) the role of Ca2+ release from the sarcoplasmic reticulum; and
      (3) the role of L-type Ca2+ current (I(Ca,L)). New observations on these topics
      seem to make the scenario of the pacemaker mechanism increasingly complex.
      However, such complexity and diversity of ionic events and their orchestration
      may be important for the sinoatrial node to perform its robust pacemaking
      activity under a variety of pathophysiologic circumstances.

PMID- 12521352
TI  - Induction of supraventricular tachycardia by ventricular pacing: what is the
      mechanism?

PMID- 12521353
TI  - Atrioventricular sequential pacing by an implantable cardioverter defibrillator
      during sustained ventricular tachycardia: what is the mechanism?

PMID- 12521354
TI  - Three-dimensional visualization of phase singularities on the isolated rabbit
      heart.

PMID- 12521355
TI  - Bidirectional ventricular tachycardia.

PMID- 12521356
TI  - Bupropion for the treatment of tobacco dependence: guidelines for balancing risks
      and benefits.
AB  - Tobacco use, particularly cigarette smoking, is now a global pandemic. The
      expected morbidity and mortality from smoking-attributable diseases will continue
      to rise for the next 30 years. In order to reduce this negative impact on
      worldwide health, effective therapy to aid smoking cessation must be provided to
      current smokers. Treatment for tobacco dependence involves the combination of
      behavioural therapies and pharmacological treatment. The most common
      pharmacological treatments include nicotine replacement therapy and non-nicotine
      medications, including antidepressants. The antidepressant with the greatest
      weight of evidence for efficacy in the treatment of tobacco dependence is
      bupropion. Sustained-release bupropion is approved for the treatment of tobacco
      dependence in over 50 countries worldwide. The efficacy of bupropion for the
      treatment of tobacco dependence is attributed to the blockage of dopamine
      reuptake in the mesolimbic dopaminergic system. This area of the brain is
      believed to mediate reward for nicotine use and for other drugs of dependence.
      Randomised, controlled clinical trials have shown that bupropion approximately
      doubles abstinence rates compared with placebo. In addition, long-term treatment
      with bupropion may reduce or delay smoking relapse. Bupropion also appears to be
      effective in the treatment of smokers who have recently relapsed and smokers with
      other comorbid psychiatric conditions. Bupropion has a good adverse events
      profile, but the risk exists for serious adverse effects such as seizures. Recent
      postmarketing surveillance reports have raised safety concerns about bupropion,
      although no causal relationship between bupropion and the reported serious
      adverse events or death has been established.

PMID- 12521357
TI  - Pharmacological treatment of vertigo.
AB  - This review discusses the physiology and pharmacological treatment of vertigo and
      related disorders. Classes of medications useful in the treatment of vertigo
      include anticholinergics, antihistamines, benzodiazepines, calcium channel
      antagonists and dopamine receptor antagonists. These medications often have
      multiple actions. They may modify the intensity of symptoms (e.g. vestibular
      suppressants) or they may affect the underlying disease process (e.g. calcium
      channel antagonists in the case of vestibular migraine). Most of these agents,
      particularly those that are sedating, also have a potential to modulate the rate
      of compensation for vestibular damage. This consideration has become more
      relevant in recent years, as vestibular rehabilitation physical therapy is now
      often recommended in an attempt to promote compensation. Accordingly, therapy of
      vertigo is optimised when the prescriber has detailed knowledge of the
      pharmacology of medications being administered as well as the precise actions
      being sought. There are four broad causes of vertigo, for which specific regimens
      of drug therapy can be tailored. Otological vertigo includes disorders of the
      inner ear such as Meniere's disease, vestibular neuritis, benign paroxysmal
      positional vertigo (BPPV) and bilateral vestibular paresis. In both Meniere's
      disease and vestibular neuritis, vestibular suppressants such as anticholinergics
      and benzodiazepines are used. In Meniere's disease, salt restriction and
      diuretics are used in an attempt to prevent flare-ups. In vestibular neuritis,
      only brief use of vestibular suppressants is now recommended. Drug treatments are
      not presently recommended for BPPV and bilateral vestibular paresis, but physical
      therapy treatment can be very useful in both. Central vertigo includes entities
      such as vertigo associated with migraine and certain strokes. Prophylactic agents
      (L-channel calcium channel antagonists, tricyclic antidepressants, beta-blockers)
      are the mainstay of treatment for migraine-associated vertigo. In individuals
      with stroke or other structural lesions of the brainstem or cerebellum, an
      eclectic approach incorporating trials of vestibular suppressants and physical
      therapy is recommended. Psychogenic vertigo occurs in association with disorders
      such as panic disorder, anxiety disorder and agoraphobia. Benzodiazepines are the
      most useful agents here. Undetermined and ill-defined causes of vertigo make up a
      large remainder of diagnoses. An empirical approach to these patients
      incorporating trials of medications of general utility, such as benzodiazepines,
      as well as trials of medication withdrawal when appropriate, physical therapy and
      psychiatric consultation is suggested.

PMID- 12521358
TI  - Stimulation of the nervous system for the management of seizures: current and
      future developments.
AB  - Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to
      have started from the theory that since VNS can alter the EEG, it may influence
      epilepsy. It proved effective in several models of epilepsy and was then tried in
      short-term, open-label and double-blind trials, leading to approval in Canada,
      Europe and the US. Follow-up observations in these patients demonstrated
      continued improvement in seizure control for up to 2 years. Close to 50% of
      treated patients have achieved at least a 50% reduction in seizure frequency.
      This therapy was also useful as rescue therapy for ongoing seizures in some
      patients; many patients are more alert. The initial trials were completed in
      patients >/=12 years of age with refractory partial seizures. Subsequently,
      similar benefits were shown in patients with tuberous sclerosis complex, Lennox
      Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures.
      Implanting the generator and leads is technically easy, and complications are
      few. The method of action is largely unknown, although VNS appears to alter
      metabolic activity in specific brain nuclei. Considering that improvement in mood
      is frequently found in patients using VNS, it has undergone trials in patients
      with depression. Other illnesses deserving exploration with this unusual therapy
      are Alzheimer's disease and autism. Some aspects of VNS have proven
      disappointing. Although patients have fewer seizures, the number of antiepileptic
      drugs they take is not significantly reduced. In addition, there is no way to
      accurately predict the end of life of the generator. Optimal stimulation
      parameters, if they exist, are unknown. Deep brain stimulation is a new method
      for controlling medically refractory seizures. It is based on the observation
      that thalamic stimulation can influence the EEG over a wide area. Several
      thalamic nuclei have been the object of stimulation in different groups of
      patients. Intraoperative brain imaging is essential for electrode placement. The
      procedure is done under local anaesthesia. Experience with this therapy is
      currently limited, but growing.

PMID- 12521360
TI  - Opinion and evidence in neurology and psychiatry.

PMID- 12521359
TI  - Compliance with stimulants for attention-deficit/hyperactivity disorder: issues
      and approaches for improvement.
AB  - Attention-deficit/hyperactivity disorder (ADHD) affects approximately 8-10% of
      school-aged children in the US and for many individuals persists into adolescence
      and adulthood. Both pharmacological and nonpharmacological (behavioural)
      therapies are used to treat individuals with ADHD. Treatment with stimulant
      medications, which include methylphenidate and amphetamine, typically requires
      multiple daily doses to maintain efficacy. The frequency of treatment, coupled
      with the importance of timing of doses and the long-term nature of treatment,
      make noncompliance a particular issue in the treatment of ADHD. Studies report
      noncompliance rates of 20-65% with stimulant treatment, although there are only
      limited published studies and these show considerable individual variation.
      Noncompliance can arise through inadequate supervision of those receiving
      medication, leading to delayed or missed doses, or through the reluctance of
      individuals to take medication, which is influenced by a number of factors (e.g.
      social attitudes, pressures or worries surrounding medication use and the
      inconvenience of multiple daily doses). Two approaches are likely to increase
      compliance with stimulant treatment: effective once-daily formulations of
      medication and improved treatment information. The development of effective once
      daily formulations for stimulant treatments removes the need for multiple daily
      doses, with the associated problems of ensuring adequate treatment supervision
      and personal privacy. Improved provision of education and information for
      individuals with ADHD, as well as their families and teachers, should help them
      address the issues surrounding stimulant medication and allow full participation
      in the treatment process. Together, these strategies should improve treatment
      compliance for individuals with ADHD.

PMID- 12521361
TI  - Lack of specificity of cyclosporine immunoassays. Results of a College of
      American Pathologists Study.
AB  - OBJECTIVE: To evaluate the cross-reactivity of the 6 most abundant cyclosporine A
      (CsA) metabolites in commonly used assays for CsA. DESIGN: Whole blood samples
      containing either only 62 ng/mL CsA (A) or 62 ng/mL CsA and between 49 and 86
      ng/mL of 1 of the 6 most abundant CsA metabolites (B) were lyophilized. One
      sample of A and 1 of B were mailed to each of the laboratories participating in
      the College of American Pathologists Proficiency Testing Program quarterly during
      a 3-year period (1999-2001). Method means and coefficients of variation were
      calculated for each mailing. RESULTS: The study showed significant cross
      reactivity of metabolites in all the immunoassay systems studied. Overall degree
      of interference decreased from Abbott TDx polyclonal > Abbott TDx monoclonal >
      DiaSorin > Syva EMIT. High-performance liquid chromatography methods gave results
      close to those found using mass spectrometric techniques. CONCLUSIONS:
      Significant metabolite interference was found to occur with the immunoassay
      systems studied.

PMID- 12521362
TI  - Customer satisfaction in anatomic pathology. A College of American Pathologists Q
      Probes study of 3065 physician surveys from 94 laboratories.
AB  - CONTEXT: Measurement of physicians' and patients' satisfaction with laboratory
      services has recently become a requirement of health care accreditation agencies
      in the United States. To our knowledge, this is the first customer satisfaction
      survey of anatomic pathology services to provide a standardized tool and
      benchmarks for subsequent measures of satisfaction. OBJECTIVE: This Q-Probes
      study assessed physician satisfaction with anatomic pathology laboratory services
      and sought to determine characteristics that correlate with a high level of
      physician satisfaction. DESIGN: In January 2001, each laboratory used
      standardized survey forms to assess physician customer satisfaction with 10
      specific elements of service in anatomic pathology and an overall satisfaction
      rating based on a scale of rankings from a 5 for excellent to a 1 for poor. Data
      from up to 50 surveys returned per laboratory were compiled and analyzed by the
      College of American Pathologists. A general questionnaire collected information
      about types of services offered and each laboratory's quality assurance
      initiatives to determine characteristics that correlate with a high level of
      physician satisfaction. SETTING: Hospital-based laboratories in the United States
      (95.8%), as well as others from Canada and Australia. PARTICIPANTS: Ninety-four
      voluntary subscriber laboratories in the College of American Pathologists Q
      Probes quality improvement program participated in this survey. Roughly 70% of
      respondents were from hospitals with occupied bedsizes of 300 or less, 65% were
      private nonprofit institutions, just over half were located in cities, one third
      were teaching hospitals, and 19% had pathology residency training programs. MAIN
      OUTCOME MEASURES: Overall physician satisfaction with anatomic pathology and 10
      selected aspects of the laboratory service (professional interaction, diagnostic
      accuracy, pathologist responsiveness to problems, pathologist accessibility for
      frozen section, tumor board presentations, courtesy of secretarial and technical
      staff, communication of relevant information, teaching conferences and courses,
      notification of significant abnormal results, and timeliness of reporting).
      RESULTS: The database of 3065 physician surveys was derived from 94 laboratories.
      An average of 32.6 surveys (median 30) was returned per institution, with a range
      of 5 to 50 surveys per institution. The mean response rate was 35.6% (median
      32.5%). The median (50th percentile) laboratory had an overall median
      satisfaction score of 4.4. The lowest satisfaction scores that were obtained all
      related to poor communication, which included timeliness of reporting,
      communication of relevant information, and notification of significant abnormal
      results. Statistically significant associations of customer satisfaction with
      certain institutional characteristics and laboratory performance improvement
      activities were identified. CONCLUSIONS: The importance of this satisfaction
      survey lies not in its requirement as an exercise for accrediting agencies but in
      understanding the needs of the customer (in this case the physician) to direct
      performance improvement in the delivery of quality anatomic pathology laboratory
      services.

PMID- 12521363
TI  - Hantaviruses. a short review.
AB  - OBJECTIVES: Hantaviruses are rodent viruses that have been identified as
      etiologic agents of 2 diseases of humans: hemorrhagic fever with renal syndrome
      (HFRS) and hantavirus pulmonary syndrome (HPS). This article presents a concise
      review of hantavirus biology, the medical features of HFRS and HPS, and tests for
      the detection of hantavirus infections in humans. DATA SYNTHESIS: Hemorrhagic
      fever with renal syndrome is a disease found outside the Americas and denotes a
      group of clinically similar illnesses that vary in severity relative to the
      causative agent. Hantavirus pulmonary syndrome is associated with higher
      mortality than HFRS, was first recognized as a hantavirus disease in 1993, and
      occurs within the American continents. Recent genetic studies show that both Old
      and New World hantavirus species coevolved with specific rodent hosts. The list
      of distinct hantaviruses associated with HPS is growing. The burgeoning human
      population is causing disruption of natural habitats as more and more land is
      cleared for commercial and residential purposes. Many rodents readily adapt to
      life in human settlements, where they generally benefit from reduced predation
      and where they sometimes proliferate to high numbers. CONCLUSIONS: Although often
      referred to as emerging pathogens, HPS-associated hantaviruses emerge through
      increased exposure of humans to rodents and their excreta, not through genetic
      drift or reassortment of the viral genome. Based on current human population
      growth and development trends, hantavirus diseases will become more common in the
      near future unless public health measures are taken to curtail or eliminate
      rodents from human communities.

PMID- 12521364
TI  - Male versus female breast cancers.   A population-based comparative
      immunohistochemical analysis.
AB  - CONTEXT: The rate of male breast cancer is a small fraction of that observed in
      females, thus severely limiting our understanding of the pathogenesis of this
      condition. It remains unclear whether the biological behavior and tumor
      progression associated with male breast cancer parallel that of the female form.
      OBJECTIVES: To evaluate the immunohistochemical profile of male breast carcinomas
      and to compare this profile with that of stage-matched female breast cancers.
      DESIGN: Seventy-five cases of primary male breast cancer were identified using
      the records of the Saskatchewan Cancer Foundation over a period of 26 years (1970
      1996). Fifty-nine of these cases had formalin-fixed, paraffin-embedded tissue
      blocks available for the purposes of this study. All cases were reviewed and a
      standardized modified Bloom-Richardson grading criterion was applied. Estrogen
      receptor status, progesterone receptor status, c-Erb-B2 expression, p53
      expression, and Bcl-2 expression were evaluated by immunohistochemistry. Results
      from 240 consecutive cases of stage-matched female breast cancers analyzed in the
      same laboratory were used as a standard set for comparison. RESULTS: Male breast
      cancers tended to be high grade (85% grade 3) in comparison with the female
      breast cancers (50% grade 3). In descriptive analysis across all stages of
      disease, male carcinomas were more frequently estrogen receptor positive (81% vs
      69%) than their female counterparts. Despite their high grade, they were less
      likely to overexpress p53 (9% vs 28%) and Erb-B2 (5% vs 17%) than the female
      counterparts. There was no significant difference in either progesterone receptor
      (63% vs 56%) or Bcl-2 (79% vs 76%) overexpression. Stratified analysis by stage
      matched controls showed no statistically significant differences among the men
      and women with stage I disease. However, in stage II-matched samples,
      statistically significant differences were observed between the 2 groups. The
      male cancers were more likely to overexpress estrogen receptor (81.6% vs 64.4%, P
      = .04), progesterone receptor (71.1% vs 47.5%, P = .01), and Bcl-2 (78.9% vs
      69.4%, P = .20). They also showed statistically significant lower expression of
      p53 (7.9% vs 36.3%, P = .001) and Erb-B2 (5.3% vs 23.8% P = .01). CONCLUSION:
      Male breast cancers display distinct immunophenotypic differences from those
      occurring in women, implying a different pathogenesis in the evolution and
      progression of this disease. Such differences may play key roles in therapeutic
      management, warranting different treatment strategies in comparison to female
      breast cancers.

PMID- 12521365
TI  - Flow cytometric analysis of acute leukemias.   Diagnostic utility and critical
      analysis of data.
AB  - CONTEXT: Acute leukemia displays characteristic patterns of surface antigen
      expression (CD antigens), which facilitate their identification and proper
      classification and hence play an important role in instituting proper treatment
      plans. In addition to enzyme cytochemical analysis, multiparameter flow
      cytometric analysis has become commonplace in most laboratories for that purpose.
      The essential role and caveats of flow cytometry in that regard, however, have
      received little scrutiny. OBJECTIVE: To evaluate the expression of commonly used
      immunomarkers and patterns in various acute leukemias to help define the best use
      and role of multiparameter flow cytometry in the diagnosis and proper
      classification of acute leukemias. DESIGN: We have retrospectively analyzed the
      immunophenotypic data from 508 de novo adult and pediatric acute leukemia
      patients, as studied using multiparameter flow cytometry in addition to routine
      morphologic and enzyme cytochemical analysis. Cytogenetic and/or molecular data
      were correlated in all 41 cases of acute promyelocytic leukemia (APL) and in 203
      other cases of acute leukemia where those data were available. We have also
      determined the positive and negative predictive values of a combined CD34 and HLA
      DR expression pattern for the differentiation of APL from other myeloid
      leukemias. RESULTS: In acute myeloid leukemia (AML) other than APL, expression of
      CD34 was seen in 62% and expression of HLA-DR in 86% of all cases. Twenty-six
      (10%) of 259 cases of non-APL AML were negative for both CD34 and HLA-DR as
      opposed to 33 (80%) of 41 cases of APL. None of the cases of APL were positive
      for both CD34 and HLA-DR in contrast to 149 (58%) of 259 cases of non-APL AML.
      Fifty-three cases were found to be examples of minimally differentiated AML (AML
      M0) based on the lack of expression of cytoplasmic CD3 and cytoplasmic CD79a and
      expression of one or more myelomonocytic-associated antigens and/or
      myeloperoxidase. Expression of CD20 was seen in 40 (24%) of 168 cases of
      precursor B-cell acute lymphoblastic leukemia (pB-ALL) and 52 (29%) lacked CD34
      expression. Five of 180 cases of pB-ALL and 2 cases of precursor T-cell ALL (pT
      ALL) were negative for terminal deoxynucleotidyl transferase (TdT). Aside from
      cytoplasmic CD3, CD5 and CD7 were the most sensitive antigens present in all 21
      cases of pT-ALL. CD33 was more sensitive but less specific than CD13 for myeloid
      lineage. CONCLUSION: Aside from identification of blasts, flow cytometry was
      found to be especially useful in the correct identification of AML M0,
      differentiation of APL from AML M1/M2, and correct identification of TdT-negative
      ALL and unusual variants, such as transitional B-cell ALL and undifferentiated
      and biphenotypic acute leukemias.

PMID- 12521366
TI  - Pathologic review of atypical hyperplasia identified by image-guided breast
      needle core biopsy.   Correlation with excision specimen.
AB  - CONTEXT: Management of breast needle core biopsies diagnosed as atypical ductal
      hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ is
      controversial. Current recommendations involve excisional biopsy to rule out
      ductal carcinoma in situ and/or invasive carcinoma, which have been reported in
      more than 50% of cases in some series. OBJECTIVE: To determine how frequently
      these diagnoses made on needle core biopsy are ultimately found to represent in
      situ or invasive carcinoma based on excisional biopsy specimens, in order to
      identify predictive factors. DESIGN: One thousand eight hundred thirty-six image
      guided needle core biopsies were performed between January 1, 1995 and May 1,
      2001. Fifty-four (2.9%) patients diagnosed with atypical ductal hyperplasia (n =
      36), atypical lobular hyperplasia (n = 12), atypical ductal hyperplasia +
      atypical lobular hyperplasia (n = 3), or lobular carcinoma in situ (n = 3)
      subsequently underwent breast excisions. Pathologic features were reviewed in
      each of the needle core biopsies using Page's criteria and were then correlated
      with excision specimens. SETTING: University medical center. RESULTS: Review of
      the needle core biopsy cases with either ductal carcinoma in situ or invasive
      carcinoma + ductal carcinoma in situ on final excision showed that nucleoli were
      evident in most of the needle core cases, with foci of nuclear pleomorphism and
      individual cell necrosis or apoptosis. CONCLUSION: A more precise diagnosis can
      be made by using strict criteria for atypical ductal hyperplasia versus ductal
      carcinoma in situ on needle core biopsy. Cytologic atypia, even if in a small
      area, particularly when there is apoptosis/individual cell necrosis, correlates
      with the finding of a more serious lesion on excision.

PMID- 12521367
TI  - Artifactual hyperbilirubinemia due to paraprotein interference.
AB  - CONTEXT: Paraprotein interference in automated chemistry is uncommon. We describe
      2 patients with paraproteinemia and elevated total bilirubin levels measured
      erroneously using the Roche total bilirubin assay. OBJECTIVES: To explain the
      mechanism of this artifactual hyperbilirubinemia and to determine its frequency
      in patients with monoclonal or increased immunoglobulins. MATERIALS AND METHODS:
      The assay was performed manually using serum from 2 index patients and from
      control patients (without M proteins). Total bilirubin was also determined using
      another manufacturer's assay. A prospective study was then undertaken using serum
      from 100 consecutive patients with various monoclonal gammopathies and from 13
      patients with polyclonal hypergammaglobulinemia and cryoglobulins. For all
      patients, serum immunoglobulin (Ig) G, IgA, IgM, total and direct bilirubin,
      creatinine, and a direct spectrophotometric assessment of icterus were measured.
      RESULTS: After the addition of assay reagents, a white precipitate formed in the
      reaction mixtures containing serum from the index patients, but not in other
      samples. This turbidity, rather than the expected color change to pink, increased
      the absorbance and falsely elevated the total bilirubin value. Serum from both
      index patients was anicteric, their direct bilirubin measurements were
      unaffected, and total bilirubin measured using an alternate assay was normal.
      Among the 113 patients studied, no additional spurious total bilirubin values
      were detected. CONCLUSION: Paraprotein interference with the Roche automated
      total bilirubin assay is caused by precipitate formation. This interference is
      rare and probably idiosyncratic. Spurious hyperbilirubinemia from paraprotein
      interference may cause clinical confusion. If artifactual elevation of total
      bilirubin is suspected, the laboratory should examine the specimen for icterus
      (manually or by spectrophotometry) or measure total bilirubin using a different
      method.

PMID- 12521368
TI  - Lymph node infarction.   An immunohistochemical study of 11 cases.
AB  - CONTEXT: The etiology of lymph node infarction may be difficult or impossible to
      determine by histologic examination. Lymph node infarction is followed by
      malignant lymphoma in some but not all patients. The role of immunohistochemistry
      in the evaluation of lymph node infarction is not well defined. Although it is
      widely believed that necrotic tissue is not suitable for immunohistochemical
      study, this view may be inaccurate. OBJECTIVE: To determine whether lymphoid
      antigens are preserved in infarcted lymph nodes and to determine the utility of
      immunohistochemical staining in the evaluation of lymph node infarction. DESIGN:
      Retrospective immunohistochemical study of infarcted lymph nodes using archival
      formalin-fixed, paraffin-embedded tissue. SETTING: Academic medical center.
      PATIENTS: Eleven adult patients with lymph node infarction retrieved from
      pathology files. MAIN OUTCOMES MEASURES: Results of immunohistochemistry,
      diagnosis of lymphoma. RESULTS: Preservation of lymphoid antigens was observed in
      4 of 6 cases of lymph node infarction associated with malignant lymphoma,
      including 3 of 5 cases of diffuse large B-cell lymphoma and 1 case of peripheral
      T-cell lymphoma. Nonspecific staining was not encountered. In 1 case, in which an
      infarcted lymph node showed a benign pattern of lymphoid antigen expression,
      lymphoma has not developed after 5 years. CONCLUSION: Lymphoid antigens are
      frequently preserved in cases of lymph node infarction, and immunohistochemical
      study of infarcted lymph nodes may provide clinically useful information.

PMID- 12521369
TI  - Interpretative problems and preparative technique influence reliability of
      intraoperative parathyroid touch imprints.
AB  - CONTEXT: Identification of parathyroid tissue (PT) is crucial during parathyroid
      and thyroid surgery. Touch imprint preparation (TIP) examination is potentially a
      more time-effective and less labor-intensive approach than frozen section
      examination for identification of PT during intraoperative consultation. However,
      the reliability of PT-TIP remains controversial, and this fact has hindered its
      adoption as a replacement for frozen section examination. OBJECTIVE: To assess
      the factors contributing to the relative lack of reliability of TIP in a
      retrospective study. METHODS: Fifty randomly selected, alcohol-fixed, hematoxylin
      eosin- and/or Diff-Quik-stained TIPs of specimens that had been submitted to
      confirm PT during intraoperative consultation were retrospectively reviewed by 5
      observers. The observers were blinded to the final interpretation (based on
      hematoxylin-eosin-stained permanent sections), which included PT in 39 (78%) of
      the 50 specimens, thyroid in 9 (18%), lymph node in 1 (2%), and adipose tissue 1
      (2%). Cases in which a unanimous diagnosis was not attained were re-reviewed by 3
      observers. RESULTS: Of 50 TIPs reviewed, a unanimous diagnosis was rendered in 33
      cases (66%), including 27 (69%) of 39 PT cases, 5 (56%) of 9 thyroid cases, and
      the 1 lymph node case. Cytologic features observed in the TIPs that were
      unanimously accepted as being diagnostic of PT included the presence of small
      uniform cells in isolation or in small groups, round to oval nuclei, salt-and
      pepper chromatin, occasional naked nuclei, and delicate vacuoles both within the
      cytoplasm and in the background. Re-review of the 17 remaining TIPs cases, in
      which diagnostic unanimity was not achieved, demonstrated that factors hindering
      assessment of the TIPs included hypocellularity (n = 5 cases), air-drying effect
      (n = 4), hemorrhagic background (n = 4), and presence of PT cells in follicular
      (thyroid-like) arrangements (n = 4). CONCLUSIONS: The major factors influencing
      reliability of TIP of PT during intraoperative consultation are related primarily
      to interpretative problems and preparative technique. Awareness of interpretative
      problems and attention to preparation of TIPs may further enhance the accuracy of
      TIP during intraoperative consultation.

PMID- 12521370
TI  - Misdiagnosis of high-grade vulvar intraepithelial neoplasia (VIN III) as mild
      cervical intraepithelial neoplasia (CIN I) on Papanicolaou tests.
AB  - CONTEXT: Although high-grade vulvar intraepithelial neoplasia (VIN III) is a
      clinically significant lesion, it can be overlooked because of nonspecific
      clinical findings and the fact that its cytomorphologic features mimic those of
      mild cervical intraepithelial neoplasia (CIN I). OBJECTIVE: To determine if there
      are cytomorphologic features on Papanicolaou tests that can reliably distinguish
      between VIN III and CIN I. DESIGN: Papanicolaou tests diagnosed as CIN I from
      patients with biopsy-proven CIN I were compared with Papanicolaou tests diagnosed
      as CIN I from patients with biopsy-proven VIN III but with no biopsy-proven CIN
      I. RESULTS: None of the cytomorphologic features evaluated could reliably
      distinguish CIN I from VIN III. CONCLUSION: Since the Papanicolaou test cannot be
      used to distinguish between CIN I and VIN III, the clinician must pay careful
      attention to the clinical and colposcopic findings. Further research evaluating
      the use of ancillary studies, such as human papillomavirus typing, may be useful.

PMID- 12521371
TI  - Personnel standards and quality assurance practices of biochemical genetic
      testing laboratories in the United States.
AB  - CONTEXT: It has been suggested that specific regulation of laboratories
      performing genetic testing may be needed to ensure standards and quality
      assurance, and to safeguard the rights of patients with regard to confidentiality
      and providing informed consent. Previously, a comprehensive analysis of current
      practices of molecular genetic testing laboratories was conducted, the results of
      which have assisted in the assessment of the need for regulation and its impact
      on access to testing. However, a study designed to determine clinical laboratory
      practices with regard to biochemical genetic testing has not been carried out.
      OBJECTIVE: To collect and analyze data regarding availability of clinical
      biochemical genetic testing, personnel standards, and laboratory quality
      assurance practices. DESIGN: A mail survey of biochemical genetic testing
      laboratory directors and assignment of a quality assurance score based on
      responses to genetic testing process items. SETTING: Hospital-based, independent,
      and research-based biochemical genetic testing laboratories in the United States.
      PARTICIPANTS: Directors of biochemical genetic testing laboratories (n = 133;
      response rate 68.5%). MAIN OUTCOME MEASURE: Laboratory process quality assurance
      score based on the standards defined by the American College of Medical Genetics
      Laboratory Practice Committee. RESULTS: Personnel qualifications varied, although
      all directors had doctoral degrees. The mean quality assurance score was 77%
      (range 28%-100%). Higher scores were associated with the following variables:
      test director having an MD degree versus PhD degree (P = .002), director board
      certification in biochemical genetics (P = .002), research and hospital
      laboratory versus independent laboratory setting (P < .001), and participation in
      a proficiency testing program (P = .03). Twelve percent of participants had a
      confidentiality policy, and 19% required informed consent before testing.
      CONCLUSION: The finding that a number of laboratories had quality assurance
      scores that may reflect suboptimal laboratory practices, particularly with regard
      to reporting practices, suggests that personnel qualification and laboratory
      practice standards may be in need of improvement to ensure quality in clinical
      biochemical genetic testing laboratories, as well as the appropriate clinical use
      of the test results.

PMID- 12521372
TI  - Ten-year follow-up of mammary carcinoma arising in microglandular adenosis
      treated with breast conservation.
AB  - adenosis is a rare proliferative lesion of the breast that may mimic carcinoma
      grossly and histologically. Although the lesion in its simplest form is benign,
      it can give rise to carcinoma, which may be found at the time of diagnosis in a
      minority of cases. Limited follow-up data have indicated no predisposition to
      develop subsequent carcinoma in patients treated with excisional biopsy for
      microglandular adenosis when carcinoma was not initially present. Breast
      conservation has rarely been used in patients with carcinoma arising in
      microglandular adenosis. We report here the unique 10-year follow-up of a woman
      who underwent breast conservation treatment for carcinoma that arose in
      microglandular adenosis.

PMID- 12521373
TI  - Fibrosarcoma of the ovary arising in a fibrothecomatous tumor with minor sex cord
      elements.   A Case report and review of the literature.
AB  - We report the case of a 69-year-old woman who presented with postmenopausal
      bleeding. Endometrial curettings showed complex atypical hyperplasia with focal
      well-differentiated adenocarcinoma. A computed tomographic scan of the abdomen
      revealed a right ovarian mass. Histologically, the right ovarian tumor was a
      fibrothecoma with minor sex cord elements showing focal fibrosarcomatous change.
      Fibrosarcoma of the ovary is a rare tumor that is considered to arise de novo or
      secondary to benign fibromatous tumors. Fibrothecoma of the ovary with minor sex
      cord elements is also a rare entity. To the best of our knowledge, this is the
      first reported case of a fibrosarcoma arising in a fibrothecoma with minor sex
      cord elements.

PMID- 12521374
TI  - Primary pleural synovial sarcoma.   A case report and review of the literature.
AB  - Synovial sarcoma (SS) is an uncommon soft tissue tumor that occurs primarily in
      the extremities of young adults, especially in the periarticular region. In this
      report, we describe the rare occurrence of primary SS of the pleura in a 15-year
      old boy. Histologically, the tumor demonstrated monophasic morphologic findings
      and showed positive staining with vimentin and Bcl-2 and focally for cytokeratin
      CK7. Fluorescent in situ hybridization identified t(X;18) translocation. The
      patient developed recurrences 20 months following resection of the tumor. The
      literature on this uncommon entity is reviewed, and its histogenesis,
      differential diagnoses, and cytologic features are also discussed.

PMID- 12521375
TI  - Multifocal subcutaneous phaeohyphomycosis caused by Phialophora verrucosa.
AB  - An otherwise healthy 85-year-old woman presented with purulent multifocal
      subcutaneous nodules on the dorsal side of the right forearm and hand.
      Histopathologic examination of the biopsied specimen showed a subcutaneous
      granuloma with central abscess and necrosis, consistent with phaeomycotic cyst.
      Faint brown septate hyphae and moniliform fungal elements were found in the
      granuloma. Culture of the discharge grew Phialophora verrucosa. This fungus has
      rarely been reported as a pathogen of subcutaneous phaeohyphomycosis.
      Subcutaneous phaeohyphomycosis usually presents as a single lesion. In this case
      of multifocal lesions, initial imperfect excision seems to have caused satellite
      lesions. To our knowledge, this is the first report of multifocal subcutaneous
      phaeohyphomycosis caused by P verrucosa. The disease responded to oral
      itraconazole administration.

PMID- 12521376
TI  - Marked calvarial thickening and dural changes following chronic ventricular
      shunting for shaken baby syndrome.
AB  - We report the case of a 23-year-old woman who was abused at the age of 5 months.
      She suffered from complications frequently associated with shaken baby syndrome,
      such as hydrocephalus secondary to subarachnoid hemorrhage. The patient underwent
      a procedure to place a ventriculoperitoneal shunt 3 weeks after her presentation
      with signs of abuse. The ventricular shunt remained in place throughout her life,
      and the patient received multiple revisions. She also was noted to have a
      markedly thickened calvarium on both radiographs and computed tomographic scan at
      6 years old. She died following an episode of grand mal status epilepticus. An
      autopsy was performed and her skull was found to be thickened circumferentially.
      Histologic examination revealed increased cancellous space with normal trabecular
      bone. It is hypothesized that intracranial hypotension resulting from chronic
      ventricular shunting lead to her thickened calvarium, a condition previously
      reported as hyperostosis cranii ex vacuo. Dural changes seen microscopically
      corroborate this hypothesis.

PMID- 12521377
TI  - CD83+ dendritic cells in inflammatory infiltrates of Churg-Strauss myocarditis.
AB  - Churg-Strauss syndrome (CSS) is characterized by a granulomatous vasculitis of
      multiple organs with the cardiovascular system being commonly affected. The
      initiation of the disease is not well understood, but immunologic phenomena are
      thought to contribute at least partially to the syndrome. We have studied
      endomyocardial biopsy specimens from a patient with CSS and eosinophilic
      myocarditis for characterization of infiltrating immune cells by
      immunofluorescence staining techniques and found a major population to be
      composed of CD83+CD14-CD19-CD56-HLA-DR+ dendritic cells (DCs). Further phenotypic
      characterization of infiltrating CD83+ cells in CSS myocarditis showed a surface
      profile reminiscent of immature DCs. In the same patient, the cytokine expression
      pattern of mitogen-stimulated peripheral blood mononuclear cells revealed a TH0
      response as evidenced by multiplex polymerase chain reaction, and interleukin-5
      levels were elevated in plasma analyzed by enzyme-linked immunosorbent assay.
      Thus, in this case of CSS myocarditis, we found DC-like cells in myocardial
      lesions, which may suggest that DCs are involved in the inflammatory process
      possibly triggered or sustained by an imbalance of DCs and their failure to
      confer tolerance to self-antigens.

PMID- 12521378
TI  - Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2)
      domain (APS) and SH2-B enhance insulin-receptor autophosphorylation,
      extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent
      signalling.
AB  - Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2)
      domain (APS) and SH2-B are adapter proteins and substrates that interact with the
      activation loop of the insulin-receptor (IR) kinase. These proteins are
      homologous and share substantial sequence similarity. We previously showed
      [Ahmed, Smith and Pillay, FEBS Lett. 475, 31-34], for the first time, that
      insulin-stimulated phosphorylation of APS led to interaction with c-Cbl in 3T3-L1
      adipocytes and in transfected Chinese-hamster ovary (CHO) cells. In the present
      study, we find that insulin stimulates the membrane translocation and
      phosphorylation of APS to a much greater extent than SH2-B, despite the
      structural similarity of these proteins. Expression of APS or SH2-B delays IR
      tyrosine and IR substrate (IRS) dephosphorylation. This enhancement of signalling
      is also observed downsteam of the receptor. In control cells that lack APS,
      following insulin stimulation, extracellular-signal-regulated kinase (ERK) and
      Akt kinase reach maximal activation and then decline to basal levels by 60 min.
      In contrast, in APS- and SH2-B-expressing cells, ERK and Akt kinase activation
      remains at peak levels at 60 min. These effects may occur because these proteins
      either stabilize the active conformation or prevent dephosphorylation of the IR.
      We therefore conclude that, despite the ability to couple to c-Cbl, APS functions
      as a positive regulator of IR signalling and, although SH2-B is a poor substrate
      for the IR, its association with the IR allows it to regulate pathways downstream
      of the receptor independently of its phosphorylation.

PMID- 12521379
TI  - Cloning of a new type II cytokine receptor activating signal transducer and
      activator of transcription (STAT)1, STAT2 and STAT3.
AB  - In the present paper, we report the identification of a new gene encoding a
      transmembrane protein of 520 amino acids, showing 22% amino acid identity with
      the extracellular domain of the interleukin (IL)-20 receptor. This gene, termed
      likely interleukin or cytokine receptor-2 ( LICR2 ), is located on chromosome 1,
      at 25 kb from the IL22R (IL-22 receptor) gene, and is constitutively expressed in
      most tissues. A chimaeric receptor, consisting of the extracellular domain of the
      IL-10 receptor alpha chain and the intracellular domain of LICR2, activated
      signal transducer and activator of transcription (STAT)1, STAT2, STAT3 and STAT5
      upon IL-10 stimulation, in a Janus kinase 1-dependent manner. In contrast, none
      of the IL-10-related cytokines described so far could activate LICR2-transfected
      cells, suggesting that LICR2 is a signalling receptor for a new cytokine of the
      IL-10 family.

PMID- 12521380
TI  - Gene disruption discloses role of selenoprotein P in selenium delivery to target
      tissues.
AB  - Selenoprotein P (SePP), the major selenoprotein in plasma, has been implicated in
      selenium transport, selenium detoxification or antioxidant defence. We generated
      SePP-knockout mice that were viable, but exhibited reduced growth and developed
      ataxia. Selenium content was elevated in liver, but low in plasma and other
      tissues, and selenoenzyme activities changed accordingly. Our data reveal that
      SePP plays a pivotal role in delivering hepatic selenium to target tissues.

PMID- 12521381
TI  - Solitary pancreatic tuberculous abscess mimicking prancreatic cystadenocarcinoma:
      a case report.
AB  - BACKGROUND: The incidence of pancreatic tuberculosis is extremely rare, and it
      frequently misdiagnosed as pancreatic neoplasms. The nonsurgical diagnosis of
      this entity continues to be a challenge. CASE PRESENTATION: A 33 year old male
      with six-month history of intermittent right epigastric vague pain and weight
      lost had found a solitary pancreatic cystic mass and diagnosed as pancreatic
      cystadenocarcinoma. The chest X-ray film and physical examination revealed no
      abnormalities. Abdominal ultrasound (US) examination showed an irregular
      hypoechoic lesion of 6.6 cm x 4.4 cm in the head of pancreas, and color Doppler
      flow imaging did not demonstrate blood stream in the mass. The attempts to obtain
      pathological evidence of the lesion by US-guided percutaneous fine needle
      aspiration failed, an exploratory laparotomy and incisional biopsy revealed a
      caseous abscess of the head of pancreas without typical changes of tuberculous
      granuloma, but acid-fast stain was positive. CONCLUSIONS: Pancreatic tuberculosis
      should be considered in the differential diagnosis of focal pancreatic lesions,
      especially for young people in developing countries.

PMID- 12521383
TI  - Overview of rational and individualized therapeutic strategies for non-Hodgkin's
      lymphomas.
AB  - For nearly 20 years CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)
      has been the gold standard of therapy for aggressive non-Hodgkin's lymphomas
      (NHLs), curing = 30% of patients with diffuse large-cell NHL. A variety of
      strategies are being tested to identify regimens that might increase the disease
      free survival rate for aggressive NHLs. One approach has been to intensify
      chemotherapy either by administering higher doses or by using shorter
      chemotherapy cycles. There are data suggesting that elderly patients benefit from
      CHOP given in 14-day cycles with granulocyte colony-stimulating factor. Based on
      in vitro observations that continuous exposure to cytotoxic agents can override
      multidrug-resistance pumps, several groups have studied combination chemotherapy
      regimens that include continuous 2- or 3-day intravenous infusions of cytotoxic
      agents. These studies have had short follow-up but encouraging early disease-free
      survival rates. There also has been interest in integrating monoclonal antibodies
      such as rituximab into therapies for aggressive NHLs. One randomized trial found
      CHOP/rituximab to be superior to CHOP alone in elderly patients with aggressive
      NHLs. With high-dose chemotherapy and stem cell support established as a salvage
      regimen for aggressive NHLs, many trials have evaluated the value of upfront high
      dose therapy, especially in poor-prognosis patients. Other approaches to managing
      aggressive NHLs, which appear promising but are under investigation, are
      allogeneic transplants and lymphoma vaccines. An advance in the study of lymphoid
      malignancies is the development of a lymphoma classification system, the World
      Health Organization Classification of Lymphoid Malignancies, which recognizes the
      distinct molecular, morphologic, and genetic characteristics of differential
      lymphoma subtypes. It is anticipated that accurate and specific differential
      diagnosis, coupled with recognition of important clinical prognostic factors,
      will provide useful background for selecting and designing rational (and perhaps
      individualized) therapies for patients with aggressive NHLs.

PMID- 12521384
TI  - Treatment paradigms in aggressive non-Hodgkin's lymphoma in elderly patients.
AB  - Half of the patients newly diagnosed with lymphoma are > 60 years of age and can
      thus be defined as elderly. Older patients treated for lymphoma may not tolerate
      the high-dose therapies used in younger patients, usually because of the presence
      of concomitant diseases. Diffuse large B-cell lymphoma represents > 50% of all
      lymphomas seen in elderly patients. Clinical presentation and prognostic
      parameters are identical to those described in young patients. However, response
      rate is usually lower in elderly patients compared to young patients, even if the
      patients are treated with a CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone) regimen. Therefore, event
      free and overall survival rates are shorter in the elderly patients, even if
      disease-free survival is not really shorter than in young patients. Rituximab
      added to the CHOP regimen has recently been shown to dramatically improve the
      survival of these older patients without increasing the toxicity of the
      treatment.

PMID- 12521385
TI  - Challenges in the management of Burkitt's lymphoma.
AB  - Burkitt's lymphoma and small noncleaved Burkitt's-like lymphoma are rare and are
      highly aggressive forms of non-Hodgkin's lymphoma that are characterized by
      dysregulation of the c-myc oncogene. Patients with human immunodeficiency virus
      (HIV) also appear to be at risk for developing Burkitt's lymphomas. Treatment
      options for Burkitt's lymphoma involve complex chemotherapy regimens that contain
      as many as 10 cytotoxic agents. Approximately 50%-80% of adult patients with
      Burkitt's lymphoma or small, noncleaved lymphoma can be cured with these
      intensive chemotherapy regimens, and in pediatric populations, the cure rate is
      even higher. However, a number of factors often compromise the outcome of
      patients with Burkitt's lymphoma. For instance, the high proliferation rate of
      Burkitt's lymphoma enhances the risk for tumor lysis syndrome, which results from
      metabolic imbalances, such as hyperuricemia, that occur as large numbers of
      malignant cells are lysed during cytotoxic chemotherapy. Standard treatment for
      tumor lysis syndrome includes adjustments in the chemotherapy regimen, vigorous
      hydration, administration of a uric acid synthesis inhibitor like allopurinol,
      and alkalinization. The administration of recombinant urate oxidase (rasburicase)
      also has been shown to provide effective prophylaxis against hyperuricemia in
      pediatric and adult patients with hematologic malignancies. The lifetime risk of
      developing central nervous system disease is 20%-30% for Burkitt's lymphoma.
      Consequently all chemotherapy regimens with activity in Burkitt's lymphoma
      utilize some form of central nervous system prophylaxis, such as systemic or
      intrathecal methotrexate or cytarabine. In the past, patients with HIV who
      developed Burkitt's lymphoma often received inadequate chemotherapy doses because
      of their immunosuppression. With the discovery of highly active antiretroviral
      therapy, the ability to treat and control Burkitt's lymphoma in patients with HIV
      has improved.

PMID- 12521386
TI  - Prevention and treatment of hyperuricemia in hematological malignancies.
AB  - The standard prophylactic and treatment regimen for hyperuricemia in patients
      with hematological malignancies previously included vigorous hydration, urinary
      alkalinization, and a xanthine oxidase inhibitor, allopurinol, which blocks the
      conversion of hypoxanthine and xanthine to uric acid. However, xanthine is less
      soluble than uric acid, and preexisting uric acid is not affected by allopurinol.
      The enzyme urate oxidase, not present in mammals, converts uric acid to
      allantoin, which is 5-10 times more soluble than uric acid. A new recombinant
      form of urate oxidase, rasburicase, has recently been developed. In a phase I/II
      study of rasburicase in children and young adults with hematological
      malignancies, rasburicase was demonstrated to be well tolerated at 0.2 mg/kg/day
      intravenously, had a mean T1/2 of 21.2 +/- 12.0 hours, and induced a median
      decrease in uric acid from 9.7 mg/dL to 1.0 mg/dL (P < 0.001). We recently
      demonstrated, in a randomized prospective trial comparing rasburicase versus
      allopurinol in children with hematological malignancies at high risk of tumor
      lysis syndrome, that rasburicase significantly lowered the mean uric acid area
      under the curve 0 to 96 hours (128 +/- 70 mg/dL/hour vs. 329 +/- 129 mg/dL/hour;
      P < 0.001) and 4 hours post uric acid by 86% versus 12% (P < 0.001). Furthermore,
      in the hyperuricemic group, the baseline creatinine level decreased from 144% to
      102% by 96 hours following rasburicase compared to an increase from 132% to 147%
      following allopurinol. Although the difference in effect on creatinine levels is
      not significant, the study was not designed or powered to question this effect.
      Lastly, in 510 patients with hematological malignancies at risk for tumor lysis
      syndrome who received rasburicase, only 2 (0.4%) have developed new renal
      complications requiring hemodialysis. In summary, in the prevention and treatment
      of hyperuricemia, patients with hematological malignancies at risk of tumor lysis
      syndrome appear to benefit significantly from the use of a recombinant urate
      oxidase (rasburicase).

PMID- 12521387
TI  - Metabolic abnormalities in lymphoma.
AB  - Metabolic abnormalities occur relatively frequently in lymphoma patients
      undergoing chemotherapy. These abnormalities include hyperuricemia,
      hypercalcemia, hyperphosphatemia, hypocalcemia, hypomagnesemia, hyponatremia, and
      hyperkalemia. In addition, tumor lysis syndrome can result in several metabolic
      abnormalities, leading to potential renal failure. If these syndromes are
      identified promptly, they can be corrected. Guidelines for identifying metabolic
      abnormalities in lymphoma patients, as well as management suggestions, are
      presented

PMID- 12521389
TI  - VIII International Conference on Malignant Lymphoma: June 12-15, 2002, Lugano,
      Switzerland.

PMID- 12521391
TI  - Hepatitis C virus infection and B-cell non-Hodgkin's lymphomas: more than a
      simple association.
AB  - Several studies have reported that the prevalence of the hepatitis C virus (HCV)
      infection is significantly overrepresented in patients affected by non-Hodgkin's
      lymphoma (NHL), thus suggesting that besides the well-established link with
      essential mixed cryoglobulinemia, a possible role for HCV is determining the
      development of at least some types of B-cell NHL. Such an association, however,
      seems to be limited to geographic areas where the presence of HCV is more
      relevant or endemic. According to a multistep pathogenetic model based on a large
      series of clinical, immunological, histological, and molecular evidences, an HCV
      antigen-driven polyclonal B-cell lymphoproliferation could be the initial phase
      of a process leading, in a variable time, into a true clonal disease. Particular
      genetic and environmental backgrounds could play a role in the development of a
      malignant phenotype, while specific HCV genotypes do not seem to be relevant in
      this setting. Hepatitis C virus correlated with NHL often shows some distinctive
      clinicopathological features, such as older age, liver damage, presence of
      monoclonal gammopathy (often with no clinically relevant cryoglobulinemic and/or
      rheumatoid activity), increased rate of autoimmune disorders, extranodal
      localizations, and restricted histological subtypes. Overall, the clinical
      outcome of HCV-positive NHL does not seem to be different from that of NHL
      patients without HCV infection. However, the evidence of a significant hepatic
      injury may predict a worse prognosis in these subjects.

PMID- 12521392
TI  - Hepatitis C infection and B-cell non-Hodgkin's lymphoma.

PMID- 12521393
TI  - Extended rituximab therapy for previously untreated patients with Waldenstrom's
      macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia is a low-grade lymphoplasmacytoid lymphoma
      characterized by CD20 expression on malignant cells. Several studies have
      indicated that the anti-CD20 monoclonal antibody rituximab has activity against
      this disease. Thus, we performed a prospective study in which 17 previously
      untreated patients with symptomatic macroglobulinemia were treated with rituximab
      375 mg/m2 intravenously for 4 weeks. Three months after completion of rituximab,
      patients without evidence of progressive disease received repeat 4-week courses
      of this agent. Six patients (35%) achieved a partial response after extended
      treatment with rituximab. Median time to response was 3 months. The median time
      to progression (TTP) for all patients was 13 months. One of 6 responding patients
      has progressed at 10 months, while the other 5 patients remain progression free
      with a follow-up range of > 22-40 months. Eight patients (47%) were rated as
      stable disease, and their median TTP was 9 months. Treatment with rituximab was
      well tolerated and was not associated with myelosuppression; one third of the
      patients experienced infusion-related toxicity, usually fever and chills of mild
      degree. Our prospective trial of extended rituximab therapy for previously
      untreated patients with Waldenstrom's macroglobulinemia indicates that this agent
      is active, well tolerated, and might be associated with a long period without the
      need for further treatment. Studies that will combine rituximab with chemotherapy
      or with other monoclonal antibodies might be of interest.

PMID- 12521394
TI  - Stage I-IIE primary non-Hodgkin's lymphoma of the testis: results of a
      prospective trial by the GOELAMS Study Group.
AB  - Sixteen patients with aggressive primary testicular involvement were analyzed
      separately from a prospective multicenter series of 494 patients with stage I/II
      aggressive nonlymphoblastic lymphoma. The treatment strategy included 3 cycles of
      anthracycline-based chemotherapy followed by regional radiation therapy on
      inguinal, iliac, and para-aortic lymph nodes and central nervous system (CNS)
      prophylaxis by intrathecal chemotherapy and brain irradiation. Chemotherapy was
      stratified by age group. Patients aged 18-60 years received the Groupe Ouest Est
      d'Etude des Leucemies Aigues et Maladies du Sang (GOELAMS) 02 protocol: 3 monthly
      cycles of VCAP (vindesine 3 mg/m2 day 1, doxorubicin 80 mg/m2 day 2,
      cyclophosphamide 1500 mg/m2 day 2, and prednisone 80 mg/m2 days 1-5). Patients
      aged 61-75 years received the GOELAMS 03 protocol: 3 monthly cycles of VECP-Bleo
      (vindesine 3 mg/m2 day 1, epirubicin 60 mg/m2 day 1, cyclophosphamide 750 mg/m2
      day 1, prednisone 50 mg/m2 days 1-7, and bleomycin 10 mg/m2 days 1 and 5).
      Sixteen patients had testicular involvement (3.3%). Median age was 62 years
      (range, 29-73 years). The histological subtypes were diffuse large-cell lymphoma
      in all cases. Ann Arbor stage was IEA in 11 patients, IEB in 3 patients, and IIEA
      in 2 patients. All patients achieved a complete response. One patient died from
      septic shock during the last course of chemotherapy. After a median follow-up
      period of 73.5 months, the probability of disease-free survival (DFS) and overall
      survival (OS) were 70% and 65%, respectively for all patients. Disease-free
      survival and OS were 66% and 83% in patients = 60 years of age, and 74% and 56%
      in patients > 60 years of age. Relapse occurred in extranodal sites in 4 cases
      and in abdominal lymph nodes in the last case. Relapse in the CNS occurred in
      only 1 patient and in the contralateral testis in 1 patient. We found no
      correlation between OS, DFS and extent of testicular involvement, Ann Arbor
      stage, International Prognostic Index score, or lactate dehydrogenase level. This
      is the first report of a prospective study in which treatment of testicular non
      Hodgkin's lymphoma was precisely defined at diagnosis. Compared to other series,
      a combination of orchiectomy with 3 cycles of CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone)-derived chemotherapy,
      regional radiation therapy, and CNS prophylaxis seems to improve prognosis. The
      improvement in prognosis seemed to be due in part to irradiation, including the
      pelvic and lomboaortic lymphatic areas, and in part to CNS prophylaxis.

PMID- 12521395
TI  - Testicular lymphoma: a mysterious link between the testis and the brain.

PMID- 12521396
TI  - Subcutaneous panniculitis-like T-cell lymphoma: presentation of 2 cases and
      observations.
AB  - Subcutaneous panniculitis-like T-cell lymphoma is a rare tumor of primary
      cutaneous origin representing far < 1% of all non-Hodgkin's lymphomas. The
      disease typically follows a distinctive, indolent course of recurrent, self
      healing subcutaneous nodules. These nodules mimic lipomas clinically, while
      histologically resembling a panniculitis. Alternatively, a rapidly progressive
      course might be seen with subcutaneous nodules accompanied by constitutional
      symptoms and, in some cases, the development of a potentially fatal
      hemophagocytic syndrome with significant cytopenia. This tumor is widely regarded
      as a tumor of CD8+ cytotoxic T cells with the presence of cytotoxic proteins, T
      cell-restricted intracellular antigen, and granzyme B commonly demonstrated. A
      number of modalities have been reported in the treatment of this tumor, with
      varying degrees of success. In this report, we present 2 cases of subcutaneous
      panniculitis-like T-cell lymphoma with variable clinical courses. We also review
      the literature of this unusual lymphoma.

PMID- 12521397
TI  - Subcutaneous panniculitis-like T-cell lymphoma.

PMID- 12521398
TI  - Phase I study of bryostatin-1 and fludarabine in patients with chronic
      lymphocytic leukemia and indolent non-Hodgkin's lymphoma.

PMID- 12521399
TI  - Methodological issues in measuring treatment outcome in adolescent smoking
      cessation studies.
AB  - As the prevalence of adolescent smoking and, notably, regular smoking has
      increased over the last decade, researchers and practitioners have called for a
      consideration of treatment programs to promote cessation among adolescents who
      smoke. The adolescent smoking cessation treatment field is still in its infancy,
      though. The literature addressing adolescent cessation is rather limited to date,
      often plagued by methodological problems and characterized by little success.
      Many basic methodological questions remain for researchers to address before we
      will be able to answer questions such as which treatment approaches work best for
      which adolescent smokers. The purpose of this paper is to review briefly what is
      known about adolescent smoking cessation, to identify some important
      methodological issues to consider in treatment outcome studies, and to make
      recommendations to researchers to help provide a common ground for future
      comparisons of results across studies. We will address the natural history of
      adolescent smoking cessation, treatment outcomes, validity of self-reports and
      biochemical validation, and research recommendations.

PMID- 12521400
TI  - Chronic tolerance to nicotine in humans and its relationship to tobacco
      dependence.
AB  - Chronic tolerance to any drug of abuse traditionally has been thought critical to
      understanding drug dependence. This paper reviews research on chronic
      pharmacodynamic tolerance to nicotine in humans. An overview of tolerance and a
      discussion of methodological issues are first presented, followed by examination
      of cross-sectional comparisons of tolerance between groups differing in smoking
      history, as well as the few prospective studies of change in tolerance after
      quitting smoking. The relationship of nicotine tolerance to tobacco dependence is
      then evaluated. While somewhat modest in size, the literature on chronic
      tolerance to nicotine in humans is reasonably consistent in showing clear
      evidence of tolerance to subjective mood effects but little or no tolerance to
      cardiovascular, performance or other nicotine effects, within the limitations
      inherent in most human research on tolerance. However, this research also
      indicates that chronic tolerance to nicotine is not closely associated with
      tobacco dependence: non-dependent and dependent smokers are equally tolerant;
      tolerance declines very little even years after quitting; and tolerance before
      quitting may have no relationship to clinical outcome of a cessation attempt.
      Recent research from the alcohol and substance abuse fields is consistent with
      the notion that tolerance has little clinical utility in determining dependence.
      These results question the relevance of nicotine tolerance to dependence and
      suggest that research into mechanisms of tolerance, while important for
      understanding biological adaptation, may not elucidate factors responsible for
      nicotine dependence. Future research should focus on whether dependence may be
      related to tolerance or to other, as yet unexamined, effects of nicotine,
      including conditioned tolerance effects, and on the possibility that tolerance
      may influence the early onset of dependence in teens even if apparently unrelated
      to maintenance of dependence in adult smokers.

PMID- 12521401
TI  - Factors influencing cotinine half-life during smoking abstinence in African
      American and Caucasian women.
AB  - Cotinine, the proximate metabolite of nicotine, has been identified as an
      indicator of smoke constituent exposure. Higher cotinine levels in African
      American cigarette smokers have been identified. Because African Americans
      experience disproportionate smoking-related morbidity and mortality, it is
      important to examine potential factors influencing these higher levels of
      cotinine. The current study examined selected factors of ethnicity, menthol
      cigarette preference, body composition and alcohol-use history on cotinine half
      life in 6 days of smoking abstinence in African American and Caucasian women. A 7
      day inpatient protocol was conducted in the General Clinical Research Center, in
      which day 1 was ad lib smoking and days 2-7 were smoking abstinence (n = 32).
      Plasma cotinine was measured every 8 h throughout. Average cotinine half-life was
      21.3 h, similar to previously reported 18-20 h. Three women exhibited >14 ng/ml
      cotinine after 136 h of smoking abstinence. Host factors explaining 52.0% of
      variance in cotinine half-life and associated with longer half-life were being an
      African American menthol smoker, fewer years of alcohol use and greater lean body
      mass. Among menthol smokers, baseline cotinine level and cotinine half-life were
      not significantly different in Caucasian and African American women. Intra
      individual cotinine half-life variation and CYP2A6 genotype were examined in
      substudies. To improve accuracy in correctly classifying non-smokers with
      cotinine levels, a period of at least 7 days of smoking abstinence may be
      warranted.

PMID- 12521402
TI  - Influence of long-term smoking reduction on health risk markers and quality of
      life.
AB  - We have recently published efficacy and safety data of a study using an oral
      nicotine inhaler in smoking reduction. The current analysis was undertaken to
      assess the secondary objectives of the trial: the influence of long-term smoking
      reduction on health risk markers. Four hundred healthy volunteers, unable or
      unwilling to stop smoking immediately, were enrolled in a double-blind,
      randomized, placebo-controlled trial in smoking reduction; 310 were evaluable up
      to 2 years. Participants were randomized to active or placebo inhalers as needed
      for up to 18 months, with subjects encouraged to reduce their smoking as much as
      possible; counseling took place over a 2-year period. For the current prospective
      cohort study, the number of daily cigarettes, carbon monoxide (CO), cotinine,
      cardiovascular risk factors, pulmonary function tests, and quality of life were
      compared between successful reducers (n = 25) and unsuccessful reducers (control
      group, n = 285). Success was defined as a reduction of daily cigarettes of at
      least 50% from week 6 to 2 years, verified by a decrease in exhaled CO at all
      visits compared with baseline. At 2 years, successful reducers showed a
      significantly greater decrease in cotinine levels (60% vs. 1%, p < 0.001),
      cholesterol/high-density lipoprotein (HDL) ratios (-2.42 vs. -1.67, p = 0.025),
      hemoglobin concentrations (-5.67 vs. -1.34 g/l, p = 0.023), pulse rate (-3.7 vs.
      +1.0 bpm, p = 0.043), and significantly improved general health score (9.40 vs.
      2.34, p = 0.049); whereas no difference was found in forced expiratory volume
      during 1 s (FEV1) and forced vital capacity (FVC) compared with controls. The
      benefits of long-term smoking reduction of at least 50% of daily cigarettes were
      not offset by compensatory smoking, and the marked decrease in markers of smoke
      exposure had a positive influence on several cardiovascular risk markers and
      quality of life assessments.

PMID- 12521403
TI  - A comparison of a nicotine sublingual tablet and placebo for smoking cessation.
AB  - This study assessed the efficacy and safety of a nicotine sublingual tablet in
      smoking cessation in a randomized, double-blind, placebo-controlled outpatient
      trial conducted between January 1996 and May 1997. Two hundred and forty-one
      adult smokers (> or = 10 cigarettes/day for at least 3 years) used nicotine 2-mg
      sublingual tablet (n = 120) or placebo (n = 121) for up to 6 months (a 3-month
      treatment period followed by a 3-month tapering period). Subjects who scored <7
      on the Fagerstrom Tolerance Questionnaire used 1 tablet/h (up to maximum of
      20/day), whereas subjects who scored (7 used 2 tablets/h (up to maximum of
      40/day). Brief counseling was provided at baseline and at all visits. Self
      reported abstinence was measured from week 2 onwards, confirmed by expired carbon
      monoxide (CO) levels <10 ppm at each visit (1, 2, 3 and 6 weeks and 3, 6 and 12
      months). After 6 weeks of treatment, CO-validated abstinence rates were 48% in
      the active group and 23% in the placebo group (p < 0.0001). At the 3-, 6- and 12
      month visits, abstinence rates (active vs. placebo) were 33% vs. 17% (p =
      0.0046), 21% vs. 11% (p = 0.0304) and 18% vs. 10% (p = 0.0606). Adverse events
      were mild and transient and reflected those reported with existing nicotine
      replacement formulations. We concluded that the nicotine 2-mg sublingual tablet
      was effective as a smoking cessation aid.

PMID- 12521404
TI  - Effects of smoking cessation or reduction on hormone profiles and bone turnover
      in postmenopausal women.
AB  - The purpose of this study was to prospectively evaluate the impact of smoking
      cessation on hormonal concentrations, sex hormone-binding globulin (SHBG) and
      markers of bone turnover in postmenopausal women. Sixty-six women who were either
      users or non-users of estrogen replacement therapy (ERT) were randomly assigned,
      using a weighted randomization scheme, to smoking cessation (SC) or to smoking
      cessation after 6 weeks of monitoring (wait-list control group, WLC). We measured
      hormones [estrone, estradiol, testosterone, parathyroid hormone,
      dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and
      androstenedione] and SHBG, markers of bone turnover [procollagen peptide (PINP),
      bone alkaline phosphatase (BAP), and osteocalcin (OC), N- and C-terminal collagen
      cross-links (NTx and CTx)], and cotinine, at baseline and again at 6 weeks in
      women who reported smoking cessation and in women randomized to the WLC group.
      Analyses included 20 subjects who quit or significantly reduced their smoking and
      18 subjects in the WLC group. After controlling for differences in age and ERT
      use between groups, we found a significant change in SHBG in the SC vs. the WLC
      group (-8% vs. +5%, respectively; p = 0.01), and in DHEA (-18% vs. -5%,
      respectively; p = 0.04), but not in other hormonal concentrations. We also noted
      a significant change in NTx in the SC vs. WLC group (-5% vs. +56%, respectively,
      p = 0.01), but not in other markers of bone turnover. Percentage changes in SHBG
      and NTx were correlated with changes in plasma cotinine (r = 0.48; p = 0.004 and
      r = 0.36; p = 0.04, respectively). Six weeks of smoking abstinence produces
      reductions in SHBG and NTx. This may partly explain how smoking contributes to
      osteoporosis in postmenopausal women.

PMID- 12521405
TI  - Effects of smoking status and smoking cessation on leptin levels.
AB  - Cigarette smoking is associated with lower body weight, and quitting smoking
      typically produces weight gain. An effect of chronic smoking on increasing
      leptin, a protein product associated with reducing weight, may help explain this
      influence of smoking on lowering body weight. We examined fasting serum leptin
      levels in male and female adult smokers (n = 52) and non-smokers (n = 12) as well
      as long-time ex-smokers (n = 13), with all groups similar in body mass index
      (BMI). Partial regression analyses controlling for BMI and, where relevant, age
      were used to relate leptin to indices of smoking exposure and dependence within
      the smokers, and with typical alcohol and caffeine intake in the entire sample.
      Furthermore, a subset of the smokers (n = 22) quit for at least 3 weeks, and
      changes in leptin and weight were prospectively assessed. Results showed no
      difference in mean leptin levels as a function of smoking status and no
      significant associations of leptin with smoking exposure variables after
      controlling for BMI and age. However, leptin was significantly correlated with
      alcohol intake (inversely) in women. In addition, smoking cessation increased
      leptin, the opposite change expected if leptin were responsible for weight gain,
      but again only in women and not in men. This leptin change remained significant
      after controlling for the increase in weight observed in both men and women. In
      conclusion, the influence of cigarette smoking on body weight does not appear to
      be due directly to changes in leptin levels, as there is no difference in leptin
      due to smoking status and leptin does not decline after cessation.

PMID- 12521406
TI  - Evaluation of subclinical respiratory tract inflammation in heavy smokers who
      switch to a cigarette-like nicotine delivery device that primarily heats tobacco.
AB  - Cigarette smoking remains a major public health problem. For smokers who cannot
      or do not wish to quit, few options exist to reduce health risks. A cigarette
      like nicotine delivery device that heats rather than burns tobacco might deliver
      nicotine with fewer toxins. The current study was designed to determine whether
      asymptomatic heavy smokers who did not wish to quit had improvement in lower
      respiratory tract inflammation after switching to Eclipse, a cigarette-like
      nicotine delivery device that primarily heats rather than burns tobacco. Twelve
      smokers of at least 40 cigarettes daily, asymptomatic and in good health,
      underwent paired bronchoscopies, bronchoalveolar lavages and endobronchial
      biopsies before and after 2 months of using Eclipse. Eight normal non-smoking
      individuals were evaluated on one occasion for comparison. Inflammation was
      assessed by direct inspection and by cytological parameters. Goblet cell
      metaplasia was assessed histologically. Compared to non-smokers, smokers had
      increased visible inflammation, increased recovery of inflammatory cells and
      increased percentage of goblet cells. There were significant reductions in all
      these parameters following a switch to Eclipse use, although the improvement did
      not reach the normal range. No significant differences were observed in
      peripheral blood measures. Nicotine levels were generally maintained, and exhaled
      carbon monoxide (CO) levels trended strongly upward. One individual experienced a
      transient twofold increase in CO and concurrently experienced transient
      headaches. Eclipse use may be a strategy to reduce the health risks for heavy
      smokers unwilling or unable to quit.

PMID- 12521407
TI  - Efficacy of over-the-counter nicotine patch.
AB  - This study aimed to assess the efficacy of the nicotine patch for smoking
      cessation, under simulated conditions of over-the-counter sale, absent any direct
      instruction or behavioral treatment. In a randomized, double-blind, placebo
      controlled, multicenter study, 567 smokers were randomized to an active nicotine
      patch (n = 283) or placebo (n = 284). Treatment followed a three-step program of
      21 mg/day for 6 weeks, 14 mg/day for 2 weeks and 7 mg/day for 2 weeks.
      Participants received brief written instructions, an audiotape and a written
      User's Guide. There was no other intervention and no contact with participants
      between enrollment and the primary outcome assessment at 6 weeks. Analyses were
      based on intent to treat, with lost subjects counted as failures, and claimed
      abstinence was verified by carbon monoxide measures. Use of active patch produced
      significantly higher abstinence rates. Continuous abstinence rates (subject to a
      2-week grace period) for nicotine and placebo were 19.4% and 7.0% at 6 weeks (OR
      = 3.2; 95% CI 1.8-5.4) and 15.2% and 5.3% at 10 weeks (OR = 3.2; 95% CI 1.7-5.9),
      respectively. Seven-day point-prevalence rates for nicotine and placebo patches
      were 26.1% and 7.7% at 6 weeks (OR = 4.2; 95% CI 2.5-7.0) and 23.3% and 7.7% at
      10 weeks (OR = 3.6; 95% CI 2.2-6.1), respectively. Reported adverse events were
      mild and consistent with prior observations of nicotine patch use. The nicotine
      patch was safe and effective for smoking cessation at least during 10 weeks of
      treatment under open-sale conditions, without face-to-face instruction or
      counseling.

PMID- 12521409
TI  - Primary postpartum haemorrhage.
AB  - Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. In
      the developing countries, it is responsible for the death of about 125 000 women
      each year. Death from postpartum haemorrhage is eminently preventable. It is
      essential that first-line staff are able to prevent, make early diagnosis and
      provide prompt management of primary PPH. This article focuses on the prevention
      and management of primary PPH and highlights recent developments. Relevant
      current literature using the MEDLINE search strategy was examined.

PMID- 12521408
TI  - Nicotine delivery from smoking bidis and an additive-free cigarette.
AB  - The present study was conducted to determine whether smoking bidis, an additive
      free cigarette, and conventional cigarettes caused similar biochemical,
      physiological and subjective effects. This was an open-label, within-subject
      design. In each session, subjects (n = 10) smoked a single cigarette: an
      unfiltered Natural American Spirit, an unfiltered Irie bidi, an unfiltered Sher
      bidi, or one of the participant's own brand. The presentation of the cigarettes
      was randomized. Before and up to 1 h after smoking, biochemical markers [plasma
      nicotine levels and exhaled carbon monoxide (CO)] and physiological effects of
      nicotine (heart rate and blood pressure) were measured. After smoking, subjects
      completed two standardized tests of cigarette liking and cigarette sensations.
      American Spirit (32.1 ng/ml) and Irie bidi (26.0 ng/ml) cigarettes increased
      plasma nicotine more than the participant's own brand (18.5 ng/ml). Subjects
      smoked longer and took more puffs to consume the American Spirit (452.8 s, 14
      puffs) and Sher bidi (354.4 s, 14 puffs) than the participant's own brand (297.4
      s, 10 puffs). In spite of differences in nicotine delivery, participants rated
      all cigarettes as similar in nicotine content. Overall, the results indicate that
      bidis and the additive-free cigarette delivered nicotine, CO and (presumably)
      other toxic components of tobacco smoke in equal or greater amounts than
      conventional cigarettes. These results do not support an emerging belief that
      bidi cigarettes are safer than conventional brands.

PMID- 12521410
TI  - Care management problems on the labour ward: 5 years' experience of clinical risk
      management.
AB  - This is a retrospective review of 310 reports by staff following clinical risk
      incidents on the labour ward between 1996 and 2000 in a district general hospital
      with 3600 deliveries per year. Care management problems were identified and
      Reason's model of critical incident analysis applied to classify them into person
      and system-based problems. Care management problems occurred in 165 (53%) cases,
      representing 0.9% of all deliveries. The main person-based problems were errors
      in CTG interpretation (22%), poor operative technique (22%) and non-standard
      practice/poor clinical judgement (19%). System-based problems included
      insufficient staff numbers (45%), ineffective teamwork/communication (39%) and
      inadequately maintained equipment (7%). Structured analysis of clinical incident
      reports can identify the extent and nature of obstetric care management problems
      and highlight important contributory areas potentially amenable to improvement.

PMID- 12521411
TI  - The plasma and placental levels of malondialdehyde, glutathione and superoxide
      dismutase in pre-eclampsia.
AB  - The aim of the study is to investigate the plasma and placental levels of
      malondialdehyde, glutathione and superoxide dismutase in normotensive and pre
      eclamptic pregnancies. Peripheral venous blood samples were collected before
      labour (35.3 +/- 1.1 and 34.2 +/- 3.4 weeks for normotensive and pre-eclamptic,
      respectively) and placental tissues was obtained after delivery from 34 pre
      eclampsia and 33 normotensive pregnancies. The mean plasma and placental levels
      of malondialdehyde were significantly higher, glutathione and superoxide
      dismutase levels were significantly lower in pre-eclamptic compared with
      normotensive patients (P < 0.01). The plasma and placental levels of
      malondialdehyde significantly increased, glutathione and superoxide dismutase
      significantly decreased with the increments in diastolic blood pressure. As a
      conclusion maternal circulating and placental tissue levels of lipid peroxides
      increase whereas antioxidants decrease in pre-eclampsia. The magnitude of
      oxidative stress and antioxidant changes correlate well with diastolic blood
      pressure.

PMID- 12521412
TI  - Development of an instrument to measure nausea and vomiting in pregnancy.
AB  - Severity of nausea, retching and vomiting was determined using a newly developed
      nausea and vomiting in pregnancy instrument (NVPI) in two groups of pregnant
      women at two gestational time periods. Participants at Time 1 (approximately
      gestational week 9), completed a postal questionnaire (N = 643) and those at Time
      2 (approximately 13 weeks) completed the instrument at the clinic (N = 284). The
      three scale items forming the instrument had acceptable internal reliability
      (Time 1 alpha = 0.76; Time 2 alpha = 0.82). It was noted that approximately 60%
      of women did not vomit, approximately 30% experienced no retching, but 30-40%
      experienced nausea either all the time or more than once a day. The instrument
      may prove to be useful as a research tool to study nausea and vomiting in
      pregnancy.

PMID- 12521413
TI  - Women's attitudes towards management of breech presentation at term.
AB  - Current advice on the management of breech presentation at term is that all
      uncomplicated cases should be offered external cephalic version (ECV) or an
      elective caesarean section. Clinical experience suggests that ECV is currently
      not offered as widely as advised and that the majority are delivered electively
      by caesarean section. We present the results of a patient attitude survey of term
      breech deliveries in a university teaching hospital over 12 months. The results
      show that half of respondents were not offered ECV and that two-thirds of these
      women were not eligible for ECV, either having had a previous caesarean or breech
      presentation diagnosed in labour. One-third of women, potentially suitable for
      ECV, were not made aware of their options. The majority are offered elective
      caesarean section with a small minority (10%) opting for planned vaginal breech
      delivery.

PMID- 12521414
TI  - Omphalocele and gastrochisis.
AB  - Between January 1989 and November 1996 we detected a total of 44 cases of
      anterior abdominal wall defects comprising 29 with an omphalocele and 15 with
      gastrochisis. The gestational age at antenatal diagnosis of gastrochisis (mean =
      17 weeks, 95% CI = 15-19) was significantly lower than for omphalocele (mean =
      19.0 weeks, 95% CI = 17-21). Whereas gastrochisis tended to occur in relatively
      younger mothers (mean age = 23 years), omphalocele was associated with a
      comparatively advanced maternal age (mean age = 28 years). The sensitivity of
      ultrasound detection was the same for both malformations (omphalocele = 86.2%;
      gastrochisis = 86.7%). Additional structural anomalies were found in a higher
      proportion of those with an omphalocele compared with those with gastrochisis
      (62% vs. 20%). All the three cases of chromosomal anomalies were detected in
      omphalocele fetuses with an intracorporeal liver. Perinatal mortality was higher,
      albeit nonsignificantly, among fetuses with omphalocele.

PMID- 12521415
TI  - A randomised controlled trial of outpatient versus inpatient cervical cerclage.
AB  - Fifty patients with cervical incompetence were randomised to have cervical
      cerclage either as inpatients, spending 3 days in hospital post-procedure on
      supervised bed rest or as outpatients spending the time at home on bed rest. Both
      groups had a clinical diagnosis of cervical incompetence and both had either
      McDonald or Shirodkar cerclage with mersilene tape. Both groups were given
      salbutamol tablets for tocolysis, postoperatively. There were no significant
      difference in the demographic variables between the groups such as previous
      cerclage, gestational age at insertion, parity and gestational age at delivery.
      There were also no significant differences in early complications such as
      bleeding. Most late complications were also not different, including the
      spontaneous abortion rate, premature rupture of membranes, cervical dystocia and
      preterm delivery. However, more patients in the outpatient group had premature
      contractions (26.1% vs. 4.3% P=0.0479). More patients in the inpatient group had
      a delivery of a live neonate, 86.9% vs. 78.3%, but the difference was not
      statistically significant. In conclusion, out patient cerclage appears to be a
      valid option, the higher rate of premature contraction in this group is not a
      cause for concern in view of the similar mean gestational age at delivery.

PMID- 12521416
TI  - Evaluation of the impact of current antismoking advice in the UK on women with
      planned pregnancies.
AB  - Smoking during pregnancy (active or passive) is associated with increased health
      risks to the unborn child. Current policy on antismoking advice for pregnant
      women in the United Kingdom is based essentially on written information by means
      of leaflets given to them at the first antenatal visit. We evaluated the impact
      of this policy on the smoking habits of pregnant women. A sample of 180 women
      with planned pregnancies attending antenatal clinics at two teaching hospitals in
      North London was recruited over a 6-month period. All women were provided with
      the current antismoking counselling at their first visit at the end of the first
      trimester and asked to fill in a questionnaire around mid-gestation. The study
      population included 117 (65%) women who did not currently smoke (non-smokers) and
      63 (35%) who were active smokers at the beginning of their pregnancy. Thirty-nine
      non-smokers were found to be passive smokers. Three women took up smoking during
      pregnancy. Among the smokers, 53 (84.1%) women made no change in their smoking
      behaviour during pregnancy, seven (11.1%) reduced their cigarette consumption and
      only three (4.8%) gave up smoking during the first half of pregnancy. None of the
      partners changed their smoking habits. All women were aware that smoking in
      pregnancy could be deleterious to their health and that of their fetus. Despite
      awareness of dangers of smoking, the prevalence of smoking among pregnant women
      remains very high after the first antenatal visit and the current antismoking
      policy based essentially on leaflets is not effective. Health-care professionals
      should spend more time to inform women adequately about the dangers of smoking
      and help them to quit before pregnancy.

PMID- 12521417
TI  - Neural tube defects in the Czech Republic during 1961-1999: incidences, prenatal
      diagnosis and prevalences according to maternal age.
AB  - We set out to present the incidences of the neural tube defects (anencephaly,
      spina bifida and encephalocele) and to document maternal age distribution and the
      influence of the prenatal diagnostics on incidences in neonates. We also analysed
      maternal age as a risk factor for the defects studied. This was a retrospective
      epidemiological study of neural tube defects using data from the population-based
      register of congenital malformations in the Czech Republic over the 1961-99
      period. The total number of neural tube defects detected both pre- and
      postnatally was 4696 in this period (anencephaly 1857, spina bifida 2420 and
      encephalocele 419 cases). In this period, a significant decrease (due to improved
      prenatal diagnostic efficiency) in the above-mentioned defects occurred in the
      Czech Republic. No statistically significant correlation between any of the
      particular defects and the maternal age was revealed. However, neural tube
      defects as a whole show some correlation, the probability of these defects
      occurring being higher than expected in 15- and 32-year-old mothers. By
      application of the two-sided 95% CI, statistically significant correlation was
      found in 15-, 35- and 39-year cohorts; in other age-groups above the age of 32
      years this correlation was neither confirmed nor rejected. In this study,
      maternal age as a risk factor for the origin of neural tube defects has not been
      statistically confirmed. However, probability estimate makes this correlation
      possible. Statistical methods in use reveal the risk for these defects (regarding
      their relative incidences) only in maternal age groups of 15, 35 and 39 years.

PMID- 12521418
TI  - Post-partum mental disorders: pattern and problems of management in Wesley Guild
      Hospital, Ilesa, Nigeria.
AB  - Sixty-seven consecutive women who presented with postpartum mental disorder
      within 1 year after delivery over a 5-year period in a teaching hospital serving
      rural and semi-urban communities were evaluated. All patients were followed-up
      until they defaulted or for a maximum period of 1 year after presentation. There
      were more primiparous women (43.3%) than women of other parities. In 16.4%, a
      previous history of mental disorder was elicited. Family history of mental
      disorder was present in 13.4%. Premorbidly, marital disharmony was present in
      23.9%, obstetric complications in 22.4%, neonate/infant mortality in 19.4% and
      unwanted pregnancy in 16.4%. Onset of illness occurred during the peurperium in
      majority of cases (58.2%). Schizophrenia topped the list of clinical types. Short
      term prognosis was good but defaulting rate was high. Breastfeeding was stopped
      permanently by nine patients and two babies died. Ten husbands deserted their
      wives. The pattern of postpartum mental disorders has remained stable in the past
      two decades. Although the cause and effect relationship is difficult to establish
      in our study, the relative stability of some sociocultural factors suggests their
      usefulness in planning preventive strategies. A multidisciplinary approach is
      essential.

PMID- 12521419
TI  - Maternal height and labour outcome.
AB  - The aim of this study was to assess if maternal height has an effect on duration
      of labour, mode of delivery and birth weight. This was a retrospective analysis
      of casenotes of 1000 white primigravidae in a district general hospital.
      Spearman's rank correlation coefficient, logistic regression analysis, and
      Pearson's correlation coefficient was used to determine the relation between
      height and duration of labour, height and mode of delivery and birth weight,
      respectively. Odds ratio was used to quantify the association. There was no
      significant association between height and duration of labour. There was a
      statistically significant positive correlation between height and birth weight
      and a negative association between height and incidence of caesarean sections. A
      cut-off height of 160 cm is proposed as a screening tool to predict a need for
      caesarean section.

PMID- 12521420
TI  - Road traffic accidents in pregnancy in Southwest Nigeria: a 21-year review.
AB  - A 21-year (1980-2000) retrospective review of 84 pregnant women involved in road
      traffic accidents in Southwest Nigeria was conducted. Case notes of these 84
      pregnant women treated at the Obafemi Awolowo University Teaching Hospitals
      Complex, Ile-Ife, were studied. Pregnant women formed 0.3% of all individuals
      involved in accidents during the study period compared to 7% reported in
      developed countries. The fetal death rate of 3.6% and maternal death rate of 2.4%
      in this study were lower than the fetal death rates of 57% and maternal death
      rate of 8-16% reported in developed countries. There was no obvious injury in
      23.8%, while in 76.2% there were serious maternal injuries ranging from limb
      fractures, pelvic bone fracture, quadriplegia, uterine rupture, abruption
      placenta, lacerations, etc. Fetal tachycardia was observed in 11.9%. Despite
      these injuries, the majority (80.9%) achieved spontaneous vaginal deliveries;
      16.7% were lost to follow-up, while 2.4% had an emergency caesarean section for
      reasons unrelated to the accidents. Preventive measures such as proper screening
      of drivers before issuing driving licences, separation of vehicular and
      pedestrian traffic, installation and enforcement of the use of seat belts,
      restrictions of alcohol ingestion while driving, use of a crash helmet by
      cyclists would drastically reduce the incidence of these accidents.

PMID- 12521421
TI  - A multicentre review of the tension-free vaginal tape procedure in clinical
      practice.
AB  - A multicentre study was conducted to determine the success of the TVT in a
      clinical practice and to try to identify factors which may be associated with
      operative failure or postoperative complications. Three hundred and twenty women
      were included; the overall subjective success rate was 92.2%; 245 patients had
      reliable documentation regarding postoperative voiding, 25 had voiding problems
      (10.2%). Operative success did not appear to be diminished by previous surgery.
      Increased patient weight had a positive effect on outcome. Irritative symptoms
      preoperatively had an odds ratio of 1.8 for postoperative voiding difficulties.
      This study shows that the TVT appears to be an effective operation for genuine
      stress incontinence with low intra and postoperative complication rates. These
      results also show that it is highly successful in patients who may not be ideal
      candidates for other continence procedures either because of previous pelvic
      surgery or body weight.

PMID- 12521422
TI  - Quality of life studies in unselected gynaecological outpatients and inpatients
      before and after hysterectomy.
AB  - Quality of life was measured in 348 women attending gynaecological outpatients
      using EuroQol 5D. Their responses were compared to the results taken from a UK
      national questionnaire (Kind et al., 1998). Quality of life was then measured in
      131 women before and after hysterectomy. Of the outpatient group 50% of the women
      reported problems with pain and 40% with depression which were significantly more
      than a representative sample of normal UK women. Women undergoing hysterectomy
      reported similar preoperative levels of pain and depression. However, 6 months
      postoperatively there were significantly fewer women complaining of both pain and
      depression. Mean calculated scores of self-rated quality of life improved
      significantly from 0.72 preoperatively to 0.89 postoperatively (P < 0.0001). In
      conclusion, quality of life can be simply quantified using the EuroQol instrument
      and is suitable for gynaecological patients. Hysterectomy for the treatment of
      benign conditions improves the overall quality of life for the majority of women.

PMID- 12521423
TI  - Fine needle aspiration cytology compared with open biopsy histology for the
      diagnosis of azoospermia.
AB  - This was a comparative study to determine the diagnostic value of fine needle
      aspiration of the testis compared with open testicular biopsy in azoospermic men.
      A total of 34 infertile, azoospermic patients aged from 26-54 years underwent
      concurrent testicular fine needle aspiration (FNA) and biopsy. The testis was
      aspirated at three separated sites (upper, middle and lower pole) using a 20 ml
      syringe and 21-G butterfly needle. A testicular biopsy was taken from the same
      sites. Samples obtained from FNA were air-dried and stained with Romanowsky-May
      Grunwald-Giemsa method. Sections obtained from testicular biopsy were stained
      with haematoxylin and eosin (H&E). The patient's history, semen analyses,
      hormonal profile and testicular volume were analysed, and in addition to the
      histological results azoospermia was classified into obstructive and non
      obstructive. A good correlation between cytological smears and histological
      sections was found in 65 of 68 testes (95.6%). Normal spermatogenesis was
      diagnosed in seven patients (20.6%), hypospermatogenesis in nine (26.5%), late
      maturation arrest in five (14.7%), early maturation arrest in three (8.8%) and
      Sertoli only-cell in 10 (29.4%) patients. Discordance between cytology and
      histology was observed in three of 68 testes (4.4%) and was related to inadequacy
      of FNA. Testicular fine needle aspiration is a simple, minimally-invasive
      procedure that can diagnose accurately testicular function. In addition to the
      testicular volume and hormonal status, it can differentiate the obstructive from
      non-obstructive azoospermia. In cases of non-obstructive azoospermia, multiple
      passes with a fine needle can be performed instead of open testicular biopsy for
      sperm extraction if present.

PMID- 12521424
TI  - Short-term and long-term follow-up of abdominal sacrocolpopexy for vaginal vault
      prolapse: initial experience in a district general hospital.
AB  - The aim of this study was to evaluate the short-term and long-term outcome with
      patients' satisfaction of abdominal sacrocolpopexy performed on our initial 11
      patients for vaginal vault prolapse. All patients included in this study
      underwent surgery at a district general hospital and was performed by one
      experienced clinician (co-author). A retrospective analysis was performed on all
      11 consecutive women who underwent abdominal sacrocolpopexy for vaginal vault
      prolapse between September 1996 and January 1997 and were followed-up at 6 months
      and at 5-year intervals. Our initial experience reveals that abdominal
      sacrocolpopexy is a safe and effective method in the treatment of
      posthysterectomy prolapse of the vaginal vault. It is associated with a low
      incidence of intraoperative and immediate postoperative complications and
      recurrent vault prolapse. Latent stress incontinence may be unmasked and
      preoperative urodynamic evaluation is therefore recommended. Our study also
      agrees with the other studies in that co-existent cystocoele, rectocoele and
      enterocoele should be corrected at the same setting. Following this series we
      have modified our technique to reduce postoperative complications such as graft
      erosion, which is being analysed separately. It finally concludes that this
      operation should be considered by every gynaecologist and that it can be
      performed in any district general hospital.

PMID- 12521425
TI  - Who are the women who default from colposcopy clinics?
AB  - Compliance at colposcopy clinics is an essential factor for effectiveness of a
      cervical screening programme. However, there is not enough research on women who
      default from the colposcopy clinic. In this study, we have looked at some of the
      factors which might influence non-attendance at colposcopy clinics. We found that
      women who were younger and nulliparous appeared to be at greater risk of non
      attendance than older and parous women. Women tend to miss follow-up appointments
      rather than primary appoints and none of them missed treatment appointments.
      There was no relation between non-attendance and grade of the lesion. We were not
      able to assess other factors such as smoking, socio-economic status or marital
      status in this study due to inadequate documentation.

PMID- 12521426
TI  - Prevalence and determinants of contraceptive practice in a defined Nigerian
      population.
AB  - This study investigates the prevalence and determinants of contraceptive practice
      in Ile-Ife, Nigeria. A prospective study of 500 rural women in the reproductive
      age group was conducted between April to June 1999 in the Igboya health district
      of Ife central local government area of Osun State. A comprehensive contraceptive
      promotion and distribution had been carried out in this area by the University
      Teaching Hospital, the State Ministry of Health and many non-governmental
      organisations in the past 10 years. It is therefore expected that the
      contraceptive awareness and use in this environment would be high. Unfortunately,
      although all the respondents (100%) were aware of contraception and 78% were
      sexually active, only 18.8% used contraception. A majority of the non-users gave
      no reasons for failure to use contraception. Among reasons given by others
      include fear of side effects, no need for contraception, not married, religion,
      need for more children and student status. The most common contraceptive method
      among users was intrauterine contraceptive device followed by pills, condoms and
      injectable contraceptives. Factors which were significantly associated with
      utilisation of contraception were availability of family planning services,
      parity, knowledge of contraception and child spacing (P < 0.05). Religion,
      literacy level, attitudes of family planning providers and distance to family
      planning services were not found to be significant (P > 0.05). Recommendations
      that will improve wide contraceptive usage are preferred.

PMID- 12521427
TI  - The effect of hysterectomy on urinary symptoms and residual bladder volume.
AB  - This was a prospective, clinical study to evaluate the effect of abdominal and
      vaginal hysterectomy for benign indications on urinary symptoms and residual
      bladder volume. One hundred and seven women undergoing hysterectomy for benign
      conditions were included in the study that took place in a district general
      hospital between April 1998 and January 2000. Urinary symptoms such as stress
      incontinence of urine, urgency, frequency, nocturia, sensation of incomplete
      voiding and voiding difficulties were considered. A questionnaire was filled out
      and the residual bladder volume measured with a 'Bard' bladder scanner on three
      occasions-before the operation, postoperative days 3 or 4 and at the 6-week
      postoperative visit. Statistical analysis involved using a generalised estimating
      equation and significance assessed at the 5% level. Each woman acted as her own
      control. There was no evidence of changes in nocturia and voiding difficulties
      after surgery. All other symptoms and residual bladder volumes decreased
      significantly postoperatively. The type of hysterectomy did not have an effect.

PMID- 12521428
TI  - Mortality and morbidity associated with misdiagnosis of ectopic pregnancy in a
      defined Nigerian population.
AB  - Ectopic pregnancies can be very difficult to diagnose at initial admission. This
      paper reviewed the morbidity and mortality associated with misdiagnosis of
      ectopic gestation over a 15-year period (1985-99) at Ile-Ife, Nigeria. There were
      380 confirmed ectopic pregnancies of 35 857 live births, giving an incidence of
      10.5 per 1000 live births. Of the 380 cases, 38 (10%) were misdiagnosed initially
      at presentation. Mistaken diagnoses include pelvic inflammatory diseases,
      cholera, acute appendicitis, typhoid enteritis, incomplete septic abortion,
      uterine fibroid with menorrhagia, malaria, gastroenteritis, peptic ulcer and
      intestinal obstruction. There were five maternal deaths among the 38 misdiagnosed
      cases compared to two maternal deaths among the 342 initially correctly diagnosed
      cases. Significant morbidity included prolonged hospital stay, increased hospital
      costs and an enterocutaneous fistula. To improve the chances of correct diagnosis
      at initial admission, accurate menstrual and sexual history should be obtained.
      Facilities for improved diagnosis such as serum beta HCG and transvaginal
      ultrasonography should be provided. Colleagues from other specialities should be
      educated to increase their suspicion of ectopic pregnancy in any woman of
      childbearing age and perform the appropriate investigations.

PMID- 12521430
TI  - Cutaneous endometriosis and its association with caesarean section and
      gynaecological procedures.

PMID- 12521429
TI  - Referral to treatment time interval for patients with endometrial cancer in a
      district general hospital.

PMID- 12521431
TI  - Labial adhesions following normal delivery.

PMID- 12521432
TI  - Laparoscopic cholecystectomy in third trimester of pregnancy.

PMID- 12521433
TI  - Post-partum toxic shock syndrome due to an unexpected source.

PMID- 12521434
TI  - Apparent absence of lochia after elective caesarean section.

PMID- 12521435
TI  - Prostaglandin E2 induction of labour proceeding to vaginal delivery after two
      previous caesarean sections.

PMID- 12521436
TI  - Stress fracture of rib in pregnancy: what analgesia?

PMID- 12521437
TI  - Uterine fibroids and adenomyosis in a woman with Rokitansky-Kuster-Hauser
      syndrome.

PMID- 12521438
TI  - Angiomyofibroblastoma of the vulva occurring in a teenaged girl.

PMID- 12521439
TI  - Haemangiopericytoma of the sigmoid mesocolon. An unexpected finding during
      laparoscopic tubal evaluation.

PMID- 12521440
TI  - Torsion of an appendix epiploica: a rare cause of acute abdominal pain.

PMID- 12521441
TI  - Ovarian pregnancy: an unusual presentation of an uncommon condition.

PMID- 12521442
TI  - Brenner tumour arising from the wall of a mucinous cystadenoma.

PMID- 12521443
TI  - Ectopic pregnancy in the levonorgestrel releasing intrauterinesystem (LNG-IUS)
      user: atypical presentation.

PMID- 12521444
TI  - Vaginal evisceration: a report of two cases.

PMID- 12521445
TI  - Magnetic resonance appearances of ovarian fibroma with myxomatous changes.

PMID- 12521446
TI  - Treatment of intractable vaginal bleeding with formaldehyde soaked packs.

PMID- 12521447
TI  - A case of bilateral primary endometroid adenocarcinoma of the fallopian tubes.

PMID- 12521448
TI  - Two case reports of ovarian cancer after long-term tamoxifen treatment for breast
      cancer.

PMID- 12521449
TI  - Chemotherapy for ovarian adult granulosa cell tumour with synchronous endometrial
      adenocarcinoma.

PMID- 12521450
TI  - A randomised prospective trial of the obstetric forceps versus vacuum extraction
      using defined criteria.
AB  - The objective of this study was to determine the safety of obstetrics forceps
      when used under strictly defined criteria compared to vacuum extraction for
      delivery in the second stage of labour. A randomised prospective trial was
      performed on 442 women undergoing instrumental delivery in the second stage. Two
      hundred and four women were in the forceps group and 238 in the vacuum group.
      When using forceps traction efforts to deliver the baby were kept to less than
      three and the head was always delivered in the occipito-anterior position. In the
      two groups there were no significant difference in the incidence of third-degree
      perineal tears, post-partum haemorrhage or ruptured uterus. Cervical tears were
      slightly higher in the forceps group. Babies delivered by vacuum extraction
      showed a higher incidence of cephalhaematomas. There was no significant
      difference in babies needing resuscitation at birth, admission to neonatal
      intensive care unit, stillbirth or neonatal death rates. The failure rate was
      significantly higher in the vacuum group. The time taken to complete the
      procedure was significantly less in the forceps group. Forceps deliveries when
      performed under defined criteria are as safe as vacuum deliveries to the mother
      with a lesser failure rate and a lower incidence of cephalhaematomas in the
      neonate compared with vacuum deliveries.

PMID- 12521451
TI  - The 'Severe Hypertensive Illness in Pregnancy' (SHIP) audit: promoting quality
      care using a high risk monitoring chart and eclampsia treatment pack.
AB  - We set out to measure the standards of care in a regional cohort of women with
      severe hypertensive illness of pregnancy and to subsequently improve the quality
      of care using a series of interventions. This was a multi centre cyclical
      criterion audit involving 21 maternity units in the West Midlands Region.
      Prospective data collection involved named co-ordinators in each unit using
      customised proformas. Intervention comprised feedback of baseline results to each
      hospital, a monitoring chart and eclampsia treatment pack. The first audit period
      (n = 183) was for a 4-month period between 1/9/96 and 31/12/96 and the second
      audit period (n = 111) was during the same 4-month period 1 year later. Although
      compliance with the audit standards set increased in all but one standard, there
      is clearly a need to make further improvements in the quality of care
      administered.

PMID- 12521452
TI  - Induction or caesarean section for preterm pre-eclampsia?
AB  - Controversy continues over the mode of delivery in severe pre-eclampsia remote
      from term. The aim of this study was to assess prospectively the mode of delivery
      in severe pre-eclampsia remote from term. The clinical data of 108 women who
      presented consecutively with severe pre-eclampsia over a 1-year period was used
      for the study material. Sixty-eight (63%) patients were delivered by elective
      caesarean section and 40 (37%) underwent induction of labour. Twenty-six had a
      vaginal delivery following induction, the others (n = 14) had emergency caesarean
      section. No baby with a gestational age of < or = 27 weeks survived after
      delivery. Perinatal mortality was highest for the babies delivered following
      induction of labour (vaginal delivery vs. caesarean section after induction of
      labour, P = 0.0004; vaginal delivery vs. elective caesarean section, P = 0.002).
      Severe pre-eclampsia remote from term is associated with a high caesarean section
      rate. In this study, carried out in a developing country, elective caesarean
      section contributed to a better perinatal outcome than vaginal delivery or
      emergency caesarean section following induction of labour.

PMID- 12521453
TI  - Conservative management of early-onset pre-eclampsia and fetomaternal outcome in
      Nigerians.
AB  - The aim of this study was to determine the effect of conservative management of
      pre-eclampsia with onset in the second trimester on fetomaternal outcome. This
      was a prospective study of 749 consecutive cases of pre-eclampsia seen over a 5
      year period in a tertiary care centre in Enugu, Eastern Nigeria. One hundred and
      seventy-five (23.4%) of the 749 cases started at less than 30 weeks' gestational
      age. These early-onset cases formed the study group, while the remaining 574 with
      onset at 30 weeks' gestation or later (the late-onset cases) served as controls.
      The two groups were compared for some fetomaternal outcome variables at the 95%
      confidence level. Ninety-one (52%) of the early-onset group had pure pre
      eclampsia while the remaining 84 were thought to have pre-eclampsia superimposed
      on chronic hypertension. The mean gain in gestational age in the early-onset
      group was 8.8 +/- 1.5 (range: 0-19) weeks. Compared to the late-onset group, the
      early-onset group had a twofold increase in maternal mortality ratio and a
      significantly increased incidence of renal failure and HELLP syndrome. The
      perinatal mortality rate increased fourfold in the early-onset compared to the
      late-onset group due principally to prematurity and intrauterine growth
      restriction. The perinatal mortality rate was, however, comparable to results
      from similar Caucasian studies. It was concluded that there has been an increased
      incidence of early-onset pre-eclampsia in Nigerian women. Although conservative
      management of such cases may improve fetal results, it is associated with
      increased maternal mortality and morbidity because of institutional delays and
      non-availability of magnesium sulphate at the time of the study. Minimising
      institutional delays, providing magnesium sulphate and improving neonatal
      services will enhance maternal and fetal results in early-onset pre-eclampsia in
      Nigeria and are recommended.

PMID- 12521454
TI  - Who is responsible for the rising caesarean section rate?
AB  - In view of the rising trend in caesarean section rates all over the world and
      women requesting caesarean section without any medical indication, we conducted a
      questionnaire survey to assess the opinion of clinicians in the field of
      obstetrics to assess their views regarding this issue. We found that clinicians
      agree that the caesarean section rates are increasing and most of them hold the
      media and women responsible for this rising trend. However, in situations where
      no definite medical indication was evident, most of the clinicians favoured
      caesarean section. The findings of this study suggest that there is a need for
      change in the attitude of clinicians before attempting to educate women regarding
      the caesarean section for non-medical reasons.

PMID- 12521455
TI  - Maternal homocysteine levels and plasma lipids in gestational diabetes: is there
      any relationship?
AB  - The aim of the study was to investigate the possible relationship between
      maternal homocysteine levels and plasma lipid parameters and whether gestational
      diabetes can alter the serum maternal concentration of this substance. The study
      included 36 primigravidas divided into two groups: group A consisted of 21
      healthy pregnant women with a mean gestational age of 38.2 weeks, and group B
      consisted of 15 diabetic women with a mean gestational age of 38.4 weeks. No
      difference in maternal homocysteine levels was noted between the two groups
      (6.006 +/- 1.64 vs. 7.004 +/- 1.36 micromol/L). Serum cholesterol levels and
      serum triglyceride levels in normal pregnant women were not statistically
      significantly different compared to those seen in diabetic pregnant women.
      Similarly, no difference was found between the two groups regarding LDL levels
      and atheromatic index. In women with diabetes there was a weak positive relation
      between plasma concentrations of homocysteine and LDL levels as well as
      atheromatic index, but this relation was not statisticially significant. We
      conclude that serum homocysteine levels are not elevated in women with
      gestational-onset diabetes. There was also no relation between serum
      concentrations of homocysteine and lipid parameters in this complication of
      pregnancy.

PMID- 12521456
TI  - Delivery of macrosomic babies: management and outcomes of 330 cases.
AB  - This study reviews the deliveries of macrosomic babies and their outcomes. A
      total of 330 macrosomic (birth weight > or =4 kg) cases were studied
      retrospectively from July 1999 to December 1999 in the Maternity Hospital of
      Kuala Lumpur. The variables studied included induction of labour, mode of
      delivery and the incidence of maternal and perinatal complications. Three hundred
      and thirty macrosomic infants were delivered during the period of study. Vaginal
      delivery was achived in 56% of the study cases. The percentage of vaginal
      delivery was higher among those who had induction of labour (63%) compared to the
      group without induction of labour (50%). Vaginal delivery was planned in 267
      mothers and of these 69% achieved vaginal delivery. Twelve per cent of the
      macrosomic infants were delivered by elective caesarean section. Shoulder
      dystocia occurred in 4.9% of vaginal deliveries. Eighty-eight neonates were
      admitted to the special care nursery unit and 57% of these infants were delivered
      by elective caesarean section. Perineal trauma occurred in 26% of vaginal
      deliveries. Post-partum haemorrhage occurred in 32% of caesarean deliveries
      compared to 4% in vaginal deliveries. Two cases of stillbirths were documented
      but no maternal death occurred during the period of study. Vaginal delivery is
      the most frequent mode of delivery for a fetus weighing in excess of 4 kg and
      vaginal delivery should be attempted in the absence of contraindications, because
      vaginal delivery has less maternal morbidity compared to caesarean delivery.
      However, shoulder dystocia remains a significant complication of vaginal delivery
      for macrosomic fetuses.

PMID- 12521457
TI  - Delivery of the impacted head of the fetus at caesarean section after prolonged
      obstructed labour: a randomised comparative study of two methods.
AB  - Obstructed labour is a common obstetric complication in Nigeria associated with
      poor fetal and maternal outcome. Delivery of the fetus at caesarean section is
      always difficult, especially if the fetal head is impacted in the pelvis. The
      mode of delivery at caesarean section may occasionally compound the morbidity
      associated with obstructed labour. The purpose of this study was to examine and
      compare the morbidity and mortality associated with two methods of delivery of
      the impacted fetal head at caesarean section for obstructed labour (the push
      method and the pull (reverse breech) method). This study is a prospective study
      of cases of obstructed labour admitted into the labour ward of Obafemi Awolowo
      University Teaching Hospitals Complex, Ile-Ife between 1 June 1998 and May 31
      2000. One hundred and eight women with obstructed labour at term with live fetus
      undergoing caesarean section were assigned randomly to either of the methods of
      admission. The maternal and fetal outcomes were analysed and compared between
      groups. Patients in the push group had statistically significant higher rates of
      maternal morbidity (longer operation time, more blood loss, extension of uterine
      incision, endometritis, longer hospital stay and higher hospital bills) than the
      pull method (P < 0.05). Also the fetal morbidity was worse in the push group. The
      'pull' method of delivery of impacted fetal head at caesarean section for
      obstruction is safer and faster than the 'push' method.

PMID- 12521458
TI  - Abdominal delivery of the second twin.
AB  - In a series of 220 consecutive twin deliveries, 10 second twins were delivered by
      caesarean section after vaginal birth of the first, but only six survived. The
      mean time-interval between the birth of twins was 68 minutes. Because a
      protracted interdelivery interval carries risks of placental separation and
      cervical contraction, prompt trial of version of the second twin followed by
      vaginal breech extraction under anaesthesia might improve perinatal outcome.

PMID- 12521459
TI  - Ultrasound assessment of the effect of parity on postpartum uterine involution.
AB  - A longitudinal study of 300 women in the puerperium was undertaken in an African
      population. The aim was to determine the influence of parity on postpartum
      uterine diameters during involution. The patients were divided into two groups,
      nulliparous and multiparous based on parity. The uterine diameters were larger in
      the multiparous group when compared with the nulliparous group. Further analysis
      revealed positive (Pearson's) correlation between parity and uterine diameters
      and uterine volume. There was no significant correlation between parity and
      uterine volume on the 42nd puerperal day. In conclusion, Negroid patients have
      large uteri, which correlate in size positively with parity.

PMID- 12521460
TI  - Brought-in maternal deaths in south-west Nigeria.
AB  - Not all pregnant women who decide to seek care at a medical facility in Nigeria
      arrive in time to be treated. Some die while trying to get there. Data on such
      deaths are, however, scarce. In this study, conducted over a 5-year period (1995
      99), when any pregnant woman was brought in dead into the Obafemi Awolowo
      University Teaching Hospitals Complex, Ile-Ife, Nigeria, the relatives were
      interviewed immediately to discover the immediate and remote causes. Reasons
      given for late presentation include: inability to obtain transportation in time
      (41.7%), inability of the health-care staff to detect an obstetric emergency
      early enough and refer to an appropriate centre (33.3%), inability of the
      referring hospital to perform an emergency caesarean section (33.3%), fear of
      caesarean section (25%), unwillingness of drivers to travel by night (25%) and no
      money to pay for hospital costs (16.7%). Causes of death include eclampsia,
      ruptured uterus, severe postpartum haemorrhage, severe antepartum haemorrhage,
      sickle cell anaemia with crises and road traffic accidents. Prevention of
      'brought-in' maternal deaths requires social transformation, overhauling the
      health-care delivery services and improving the socio-economic status of the
      population.

PMID- 12521461
TI  - Can the New Zealand antenatal scoring system be applied in the United Kingdom?
AB  - We aimed to assess the sensitivity and predictive values of using Knox scoring in
      the United Kingdom, in order to reduce unnecessary hospital referral. One hundred
      and sixty-six pregnant women were assessed at booking by the current antenatal
      scoring as well as by Knox scoring and then the same women were reassessed at 36
      weeks' gestation. At booking Knox scored 11.7% of women as high risk while the
      current antenatal system scored 48.9%. At 36 weeks' gestation Knox scored 1.4% of
      the same pregnant women as high-risk when our scoring system identified 37.9% as
      high-risk women. We had one case of perinatal death and nine cases of perinatal
      morbidity. Knox scoring showed a higher positive predictive value (17.6% vs.
      12.1%) but less sensitivity (30% vs. 90%) than the current scoring system. That
      will lead to dramatic reduction of hospital referral at the booking visit from
      48.9% to 11.7% and late in pregnancy from 37.9% to 1.4%.

PMID- 12521462
TI  - Serum screening for anomalies in pregnancy: reasons for acceptance or refusal of
      the test.

PMID- 12521463
TI  - The management of women with apparent early ovarian cancer in the south-west
      region of England.
AB  - This study investigated the management of women with apparent early ovarian
      cancer in the South West region of England. This was retrospective review of
      prospectively collected data supplement by case note review. All women registered
      with stage 1 ovarian cancer in the 2 years from January 1997 to December 1998
      were identified from the database of the Regional Cancer Organisation (RCO). Data
      on staging and subsequent management were obtained from the RCO database.
      Additional information was collected from the patients' casenotes. We considered
      the accuracy of staging, consideration of fertility-sparing surgery, evidence of
      multidisciplinary approach to management, appropriateness of oncological referral
      and adjuvant therapy. Of 222 cases of stage 1 ovarian cancer identified from the
      RCO database, 168 casenotes were available for inspection. Eighty-seven cases
      were confirmed as FIGO stage 1 but the substage was amended in 21 cases. There
      were insufficient data available in 75 cases to confirm the stage assigned. Six
      cases were re-staged to FIGO stage 3a. Fertility-sparing surgery was considered
      in four of 10 nulliparous patients of reproductive age. Thirty-nine patients with
      disease more advanced than FIGO stage 1b were not referred for onco1 logical
      opinion. Even after Calmine-Hine guidelines are implemented, women with early
      ovarian cancer may still be treated in general hospitals. There is an urgent need
      to provide clear local guidelines for the management of these patients.

PMID- 12521464
TI  - Menstrual pattern in women with sickle cell anaemia and its association with
      sickling crises.
AB  - This was a prospective observational study based on 6-month menstrual diaries in
      women with sickle cell anaemia (SCA). The aim was to evaluate the natural
      menstrual pattern and to establish if there was an association between menses and
      painful crises in these women. The main outcome measures included length of
      cycle, duration of loss and the occurrence of painful crises in relation to
      menses. Eighty-two women were recruited initially and 42 returned completed
      menstrual diaries. A total of 213 continuous natural cycles were evaluated. The
      mean cycle length was 28.9 (+/- 5.95) days, while the mean duration of menstrual
      loss was 4.69 (+/- 4.65) days. Thirty-seven per cent of the women had definite
      cyclical painful crises with each menses and in this group, 61.5% of crises
      occurred with menstrual flow. An additional 21% had at least three cyclical
      crises documented in the 6-month period. In 42%, there was no association between
      menses and crises. In summary, 58% of women had some form of cyclical crises
      (albeit not severe) in association with menstrual cycles. In severe cases, the
      use of a continuous combined contraceptive pill regime or Depo-Provera to induce
      amenorrhoea (as well as to provide contraception) should be considered.

PMID- 12521465
TI  - Levonorgestrel-releasing intrauterine system for menstrual dysfunction: patient
      satisfaction in the district general hospital setting.
AB  - Over a 3-year period, 102 women had a levonorgestrel-releasing intrauterine
      system (LNG-IUS) inserted for menstrual dysfunction at the gynaecology clinics of
      a small district general hospital. A retrospective observation study was carried
      out to review the use of the levonorgestrel-releasing intrauterine system for
      menstrual dysfunction and patient satisfaction with the device. Sixty-six women
      felt their periods improved after insertion of the LNG-IUS. Thirty-one had the
      device removed prematurely, the most common indication being excessive bleeding.
      Nineteen underwent hysterectomy. Twenty-one experienced hormonal side effects.
      Fifty-seven of the 102 women were satisfied with the LNG-IUS and 53 would use it
      again. The continuation and satisfaction rates with the LNG-IUS at the hospital
      compare favourably with those found in research trials.

PMID- 12521466
TI  - Evaluation of menstrual and haematological parameters, after 36 months of
      Norplant contraception.
AB  - This ongoing prospective longitudinal study involved 23 women who had complete
      records, of 37 healthy non-breastfeeding informed volunteers recruited from our
      family planning clinic since August 1997 to the Norplant training programme.
      Packed cell volume (PCV), white blood cell (WBC) concentration (total and
      differential and platelet concentration were analysed at pretreatment and at 12,
      24 and 36 months' followup. Statistical analysis was with paired t-tests. The
      level of significance was set at 5%. Each acceptor received a menstrual calendar
      to document all events of bleeding. The mean PCV was 40.5 +/- 2.4% at
      pretreatment. This rose to a statistically significant (P < 0.001) mean value of
      44.9 +/- 4.4% at 36 months. The mean WBC concentration at pretreatment was 5552
      +/- 1423 per mm3 which declined statistically (P < 0.001) to a mean value of 4400
      +/- 1281 per mm3 at 12 months without any further significant changes at 24
      months (P > 0.6; 4143 +/- 1301 per mm3 and at 36 months (P > 0.9; 4070 +/- 875
      per mm3). At 24 months of study the mean concentration of neutrophils,
      lymphocytes, monocytes eosinophils and basophils did not change significantly
      from their respective mean concentrations at 12 months. These insignificant
      changes were also manifested at 36 months of study in the lymphocytes (P > 0.2),
      eosinophils (P > 0.5) and basophils (P > 0.2), even though there was a
      significant decrease in the neutrophils (P < 0.05) with a corresponding
      significant increase (P < 0.001) in the monocyte concentration. However, there
      was still a significant decrease (P < 0.001) in the WBC at 36 months of study
      compared with the mean preinsertion value, which was manifested mainly in the
      neutrophil concentration (1403 +/- 517 per mm3 (P < 0.001). The mean value of
      platelet count (136260 +/- 27664 per mm3) at 24 months showed no significant
      change compared with the 12 months value (126174 +/- 37977 per mm3). The value at
      36 months (125391 +/- 18858 per mm3), however, still showed a significant decline
      over the pretreatment mean concentration (208043 +/- 27250 per mm3). None of the
      acceptors had thrombocytopenia at 24 and 36 months. At 2 years and 3 years of
      studies 60.9% and 47.8% of Norplant users reported irregular bleeding patterns,
      mainly of reduced episodes. The continuation rate at 36 months was 100%. Women
      using the Norplant implant are at an advantage, because in spite of the variable
      aberrations in their menstrual pattern, the packed cell volume increased. The
      changes ob-served in the white cell and the platelet concentrations did not lead
      to adverse effects.

PMID- 12521467
TI  - Laparoscopic management of ectopic pregnancy: a 5-year experience.
AB  - The objective of this study was to review our management of ectopic pregnancy
      with the introduction of a laparoscopic service to the obstetrics and gynaecology
      department at South Cleveland Hospital. A retrospective analysis of 210 cases of
      ectopic pregnancy managed from May 1995 to May 2000 including operative findings
      and surgical data were collected prospectively over the past 5 years. All our
      women with an ectopic pregnancy were treated surgically. One hundred and seventy
      seven (84.3%) patients were managed successfully laparoscopically with no major
      intraoperative or postoperative complications. Thirty-three (15.7%) women were
      managed by laparotomy for various reasons. Salpingectomy was the main (80%)
      procedure performed either by laparoscopy or by laparotomy. Thirty-five (16.7%)
      women were treated conservatively by salpingostomy. Of these 22.9% achieved a
      successful pregnancy and delivery. Half of our patients were managed by senior
      registrars. The estimated blood loss, the need for blood transfusion and the
      length of hospital stay following laparoscopic treatment were significantly less
      than those in laparotomy group. This study demonstrated that laparoscopic
      management of ectopic pregnancy is the most beneficial procedure with maximum
      safety and efficiency when the laparoscopic service is added to the unit.

PMID- 12521468
TI  - Can pre-colposcopy sessions reduce anxiety at the time of colposcopy? A
      prospective randomised study.
AB  - The main objective of this prospective randomised study was to evaluate whether
      offering pre-colposcopy group sessions reduces anxiety at the time of colposcopy.
      We also examined whether this strategy improved knowledge about abnormal smears
      and colposcopy and improved satisfaction with the colposcopy service provided.
      One hundred and forty-seven women undergoing colposcopy for the first time were
      randomised into two groups. The control group (n = 75) received conventional
      management. The study group (n = 72), in addition to conventional management,
      were invited to attend a pre-colposcopy group session led by a trained colposcopy
      nurse. Questionnaires were used to determine state anxiety inventory scores and
      knowledge scores at the time of randomisation, immediately before colposcopy and
      6 weeks after the clinic visit. Satisfaction questionnaires were completed 6
      weeks after the clinic visit. We found that women attending colposcopy clinics
      are anxious. Those women who attended the pre-colposcopy session had improved
      knowledge scores (P = 0.039) at the time of colposcopy and satisfaction (P =
      0.037). However, the intervention failed to significantly reduce anxiety at the
      time of colposcopy (P > 0.05).

PMID- 12521469
TI  - Jordanian women's attitudes towards cervical screening and cervical cancer.
AB  - This paper looks at Jordanian women's attitudes towards cervical screening and
      cervical cancer. The sample consisted of 600 women attending gynaecology clinics
      at King Hussein Medical Centre, Amman, Jordan. Seventy-five per cent of women had
      never had a smear before; however, the majority agreed that it is important;
      34.5% of women did not know the significance of a positive cervical smear; 77% of
      women were not aware of causes of cervical cancer. Finally, when asked who would
      they like to take their cervical smear test, a clear preference was stated for a
      female doctor or a female nurse. These findings provide a useful background for
      developing strategies to increase the uptake of cervical smears among Jordanian
      women. It also emphasises the need to educate and promote awareness of women to
      risk factors for cervical cancer and to the need for screening programmes.

PMID- 12521470
TI  - A clinico-pathological study of complete and partial hydatidiform moles in a
      Nigerian population.
AB  - In a review of 208 cases of hydatidiform moles (HM) managed at the University
      College Hospital Ibadan, Nigeria between January 1966 and December 1996, there
      were 105 cases of complete hydatidiform mole (CHM) and 103 cases of partial
      hydatidiform mole (PHM). The ratio of PHM to CHM was 1:1. The institutional
      frequency for PHM is one per 667 deliveries, while that of CHM is one per 655
      deliveries. In contrast to CHM, the presentation of PHM was less dramatic. The
      mean age for both types of HM was 28 years, although there was a slightly
      increased difference in the population of younger patients aged (21-30 years) for
      PHM (56.3%) as against CHM (40%), respectively. The pre-evacuation uterine size
      was larger than dates in CHM (40%) compared to PHM (8%), although the mean
      gestational age was higher in PHM (19.8 weeks) when compared to CHM (15.2 weeks).
      Sixty-five patients with CHM (61.9%) presented with heavy irregular vaginal
      bleeding before evacuation compared to five patients (4.9%) with PHM. Gestational
      trophoblastic tumour (GTT) occurred in 20 patients with CHM (19.0%) compared to
      two patients (2.1%) with PHM. We conclude that the incidence of PHM is higher in
      our environment than hitherto reported and consequently there is need for greater
      awareness among health-care providers of the clinicopathological features of this
      enigmatic but interesting disease entity and development of facilities for
      routine cytogenetics. It is advisable that the follow-up period in patients with
      PHM should not be more than a year, because of the rarity of post-evacuation
      sequelae.

PMID- 12521471
TI  - Gynaecological malignancies in a rural institute in India.
AB  - A rural institutional study was carried out with the object of recording the
      number and type of gynaecological malignancies in relation to socio-economic
      status, age, parity, contraceptive use and mode of presentation in current
      gynaecological practice. Between 1985 and 1999 gynaecological malignancies
      comprised 42.52% of all malignancies in women. Cancer of the cervix (33.3%) and
      breast (27.3%), constituted 60.6% of all cancers in women. Cervical cancer (80%)
      and ovarian cancer (15%) were the main gynaecological tumours. Endometrial cancer
      was found only in 2.0% of all female genital malignancies; 76.5% women were from
      villages. Seventy-two per cent of women with gynaecological malignancies were
      from a lower socio-economic class. Nearly half (44.6%) of the overall cases
      occurred between ages of 35 and 49 years. Most women, irrespective of the site of
      cancer, were multiparous. Sterilisation had been the main birth control method
      used. Other methods of contraception had hardly been used and hence had no
      relevance to the incidence of cancers. Over the years the number of
      gynaecological cancers is increasing, irrespective of social class, with more
      cases at younger age.

PMID- 12521472
TI  - Vaginal hysterectomy after previous ventral scar hernia repair.
AB  - A series of 20 women with a previous ventral (incisional) hernia repair underwent
      successful hysterectomy by the vaginal route and 17 of them also underwent
      prophylactic oophorectomy or salpingo-oophorectomy, all without laparoscopic
      assistance. There was no trauma to the bladder or the rectum and the hernia
      repair remained intact. They were adequately counselled on the possibility of a
      switch to laparotomy or laparoscopic assistance.

PMID- 12521473
TI  - Observational case reports of intra- and postoperative ultrasound monitoring of
      uterine balloon ablation.
AB  - Uterine balloon ablation (UBT) is an established treatment of women with
      menorrhagia. Success rates in terms of amenorrhoea following UBT vary between
      about 15 and 40%. The aim of these case reports was to attempt to explain some of
      the reasons behind the low amenorrhoea rate as well as the variation seen in
      outcome. This was facilitated by intraoperative ultrasound observation of the
      position of the heater element within the uterine cavity, including its proximity
      to the endometrial walls and the direction of microbubbles produced by the heater
      element. These findings were then correlated with postoperative ultrasound
      findings and clinical outcome. The position of the balloon catheter within the
      uterine cavity varied and we hypothesise that this may have an effect on outcome.
      A thin postoperative endometrium on ultrasound signifies successful ablation, yet
      is not always associated with a cessation of troublesome menorrhagia, nor patient
      satisfaction.

PMID- 12521474
TI  - Terminating an unwanted pregnancy-the economic implications in Nigeria.

PMID- 12521475
TI  - Is 3-D ultrasound-based virtual hysteroscopy feasible?

PMID- 12521476
TI  - In utero ductal closure following near-term maternal self-medication with
      nimesulide and acetaminophen.

PMID- 12521477
TI  - Vulval carcinoma in pregnancy.

PMID- 12521478
TI  - Beware the negative pregnancy test.

PMID- 12521479
TI  - The potential consequence of early recognition and treatment of retained fetal
      bony fragments.

PMID- 12521480
TI  - Delayed presentation of a post-episiotomy rectovaginal fistula in a patient with
      Crohn's disease.

PMID- 12521481
TI  - Leiomyomatosis peritonealis disseminata-is a different approach needed?

PMID- 12521482
TI  - Allergic contact dermatitis of the vulva-an overlooked diagnosis.

PMID- 12521483
TI  - Isolated vesical endometriosis in the absence of previous surgery.

PMID- 12521484
TI  - Prolapsed leiomyoma with severe haemorrhage after GnRH analogue therapy.

PMID- 12521485
TI  - Feigned miscarriage by genital self-mutilation in a hysterectomised patient.

PMID- 12521486
TI  - Long-term survival of an advanced stage clear cell carcinoma of the endometrium
      occurring in a young woman.

PMID- 12521487
TI  - Endometrial carcinoma presenting as an adnexal mass.

PMID- 12521488
TI  - Exclusion of abnormal endometrial histology before balloon endometrial ablation:
      lessons to be learnt.

PMID- 12521489
TI  - Torsion of a normal adnexum in an adolescent.

PMID- 12521490
TI  - An atypical presentation of ovarian cancer.

PMID- 12521491
TI  - Unexplained subfertility: a pragmatic approach.
AB  - The treatment of infertility has made substantial progress over the last two
      decades. Infertility is said to be unexplained when a couple do not conceive and
      no definite cause could be identified. Unexplained subfertility continues to pose
      some difficulty in management principally because of the lack of a specific, and
      potentially treatable, abnormality and the treatment is generally empirical. In
      this review, an effort is made to define the current state of the art, efficient
      and cost-effective infertility care to permit the treatment of a larger number of
      patients suffering from unexplained subfertility within a reasonable time period.

PMID- 12521492
TI  - Could some fetocides be avoided by more prompt referral after diagnosis of fetal
      abnormality?
AB  - When a fetal abnormality has been diagnosed, a woman may be offered termination
      of pregnancy. It is important that delays in the assessment process are avoided,
      as after 21 weeks' gestation fetocide must be performed as part of the
      termination, with only a few rare exceptions. To determine whether preventable
      delays in the assessment of suspected fetal abnormalities are occurring, a
      retrospective review of all stillbirths resulting from termination of pregnancy
      in 1998 and 1999 in the North Western Region of England was conducted. There were
      47 terminations of pregnancy after 24 weeks gestation. Of these, 43 cases had
      intracardiac potassium chloride fetocide before induction of labour. One of the
      47 women was not referred to the tertiary referral centre; 39 women were referred
      within 1 week of the diagnosis of an abnormality, but in seven cases referral was
      delayed for more than 2 weeks. Inappropriate and preventable delays are
      occurring. In some cases this may mean that a woman has to undergo fetocide,
      which could have been avoided had she been referred to a tertiary centre more
      promptly.

PMID- 12521493
TI  - The effects of prenatal group genetic counselling on knowledge, anxiety and
      decisional conflict: issues for nuchal translucency screening.
AB  - This study evaluates the effects of prenatal genetic group counselling on women's
      anxiety, decisional conflict and levels of knowledge. Participants (N=271) were
      aged 35 years and older. ANOVA results indicated that pre/postcounselling scores
      for anxiety did not change significantly, while decisional conflict decreased
      significantly (P<0.001). Pre/postcounselling scores on two different knowledge
      measures were analysed using 2x3 mixed ANOVAs for time by highest level of
      education and by having discussed prenatal diagnosis with one's health care
      provider. No potential interactions were statistically significant; time alone
      had a strong significant effect for both knowledge measures (P<0.01); P<0.01,
      respectively), suggesting that the effects of the counselling intervention were
      robust. Group genetic counselling is an effective method for education and
      decision support in the prenatal context, and may serve as a model for other
      clinical populations facing genetic screening decisions.

PMID- 12521494
TI  - Serum lipoprotein (A) and apolipoproteins during pregnancy and postpartum in
      normal women.
AB  - This study was designed to investigate whether serum lipoprotein (a) is affected
      by pregnancy and to relate this to changes in other lipids, lipoproteins and
      apolipoproteins. The study involved twenty-nine healthy Caucasian pregnant women
      at term and 27 non-pregnant women matched for age who acted as controls. Samples
      of venous blood were obtained from 29 pregnant women at term (between 37 and 42
      weeks) and 22 of these women provided a second sample after 12 weeks post-partum.
      Twenty-seven non-pregnant women acted as controls. Samples were taken for Lp(a)
      and also cholesterol, triglyceride, HDL-cholesterol, apolipoprotein (apo) A and
      B1. No significant difference was found in the serum concentrations of Lp(a).
      However, the pregnant women had significantly higher serum concentrations of
      cholesterol, triglyceride, apo A1 and B (P<0.001) than the controls. The ratio of
      apo A1: apo B was significantly lower than controls (P<0.001). HDL-cholesterol
      was not altered by pregnancy but was lower (P<0.05) than the controls after a
      period of 12 weeks post-partum. Despite a hyperlipidaemia in pregnancy the serum
      concentrations of Lp(a) are not affected suggesting different metabolic control
      for this lipoprotein.

PMID- 12521495
TI  - Prenatal anger effects on the fetus and neonate.
AB  - One hundred and sixty-six women were classified as experiencing high or low anger
      during the second trimester of pregnancy. The high-anger women also had high
      scores on depression and anxiety scales. In a follow-up across pregnancy, the
      fetuses of the high-anger women were noted to be more active and to experience
      growth delays. The high-anger mothers' high prenatal cortisol and adrenaline and
      low dopamine and serotonin levels were mimicked by their neonates' high cortisol
      and low dopamine levels. The high-anger mothers and infants were also similar on
      their relative right frontal EEG activation and their low vagal tone. Finally,
      the newborns of high-anger mothers had disorganised sleep patterns (greater
      indeterminate sleep and more state changes) and less optimal performance on the
      Brazelton Neonatal Behavior Assessment Scale (orientation, motor maturity and
      depression). These data highlight the need for prenatal intervention for elevated
      angry mood during pregnancy.

PMID- 12521496
TI  - An audit of forceps delivery in Trinidad.
AB  - An audit of 247 consecutive forceps deliveries during a 6-year period was
      undertaken in order to establish trends in recourse to this instrument, maternal
      complications and fetal outcome. The chief indications were prolonged second
      stage of labour and poor maternal effort. Our overall forceps rate of 0.81%
      betrays a marked divergence from the practice in metropolitan countries. Although
      birth injuries were a major drawback, assistance with forceps still appears to be
      a safer alternative than caesarean section when a problem exists which impedes
      spontaneous delivery in the second stage. In choosing between obstetric options,
      we voluntarily take one course which we dislike because the alternative is more
      objectionable still; the unpleasantness of the choice does not destroy its
      reality.

PMID- 12521497
TI  - Early teenage pregnancy outcome: a comparison between a standard and a dedicated
      teenage antenatal clinic.
AB  - Britain has the highest rate of teenage pregnancy in the European Union. In the
      younger teenager inadequate sex education, poor knowledge of and use of
      contraception, resulting from poor home circumstances and a high school drop-out
      rate appear to be important aetiological factors. A dedicated teenage clinic can
      enhance pregnancy outcome in this group of women, and results better than those
      from a standard antenatal clinic are achievable. For this group of women, other
      sources of sex education apart from the home and schools need to be explored.

PMID- 12521498
TI  - Evaluation of emergency caesarean sections--completion of the audit cycle in a
      Central London teaching hospital.
AB  - We set out to complete the audit cycle of caesarean deliveries in order to
      determine if improvements could be achieved. This was a prospective review of
      clinical notes in a Central London Teaching Hospital. The study involved 152
      women delivering between 18 May and 23 August 1998, and 226 women over the same
      time period in 1999. For each case, a proforma was completed within 72 hours of
      delivery. We recorded the total and emergency section rate; indications; decision
      to-delivery times; reasons for delay; prescription of ranitidine and heparin;
      fetal blood samples and cord pH values. The total caesarean section rate
      decreased from 20.9% to 19.2%. The emergency section rate was unchanged at 14.8%
      in 1998 (70.9% of total) and 13.6% in 1999 (70.8% of total). Main reasons for
      emergency sections were failure to progress (59% in 1998, 47% in 1999) and fetal
      distress (27% in 1998, 34% in 1999). For failure to progress 76% of cases were
      performed within 1 hour in 1998 vs. 64% of cases in 1999. For fetal distress 39%
      of cases were delivered within 30 minutes in both years. Fetal blood samples were
      taken in 41% of fetal distress cases in 1998 and 34% in 1999. Cord pH was
      documented in 60% of emergency cases in 1998 (96% in 1999). Prescription of
      ranitidine rose from 53% to 81%. Heparin was well prescribed in both years (88%
      vs. 87%). Following the initial audit, the total caesarean section rate was
      significantly lower but there was no difference in the emergency section rate.
      The implementations had no effect on decision-to-delivery times or use of fetal
      blood sampling. Improvements were seen in obtaining cord pH values and ranitidine
      prescription.

PMID- 12521499
TI  - Transforming growth factor beta(1) levels in platelet depleted plasma in African
      women with pre-eclampsia.
AB  - Recently it has been suggested that TGF-beta(1) may play an important role in
      trophoblast invasion of spiral arteries in pre-eclampsia. This study was designed
      to investigate TGF-beta(1) levels in pre-eclampsia. Platelet depleted plasma TGF
      beta(1) levels were measured by ELISA in 43 normotensive healthy non-pregnant
      women, 30 normotensive healthy pregnant and 42 pre-eclamptic women: TGF-beta(1)
      levels were increased significantly in the pre-eclamptics (4.9+/-0.9 ng/ml)
      compared to the normotensive pregnant (1.9+/-0.54 ng/ml; P<0.001) and
      normotensive non-pregnant groups (2.1+/-0.41 ng/ml; P<0.0001). There was no
      significant difference in TGF-beta(1) levels between normotensive pregnant and
      non-pregnant groups (1.9+/-0.54 vs. 2.1+/-0.41 ng/ml; P=0.2). There was a highly
      significant correlation between neonatal weight (r=0.63; P<0.0001) and TGF
      beta(1) levels. The finding of increased levels of plasma TGF-beta(1) suggests an
      aetiological role of this peptide in pre-eclampsia.

PMID- 12521500
TI  - The role of membrane stripping in prevention of post-term pregnancy: a randomised
      clinical trial in Ile-lfe, Nigeria.
AB  - This study was carried out to evaluate the efficacy and safety of membrane
      stripping at term in reducing the incidence of post-term (41 weeks or greater)
      pregnancies. One hundred and thirty-seven pregnant women at 38 weeks gestation
      were randomised to receive either membrane stripping (69) or gentle cervical
      examination (68). Women who received stripping had earlier delivery (4.8 vs. 12.1
      days; P<0.001) and less incidence of delivery at 41 weeks or greater (3% vs. 16%;
      P=0.009). No statistically significant difference was noted in incidence of
      premature rupture of membranes, clinical evidence of chorioamnionitis,
      intrapartum characteristics and perinatal outcome. We conclude that membrane
      stripping is a safe method to reduce the incidence of post-term pregnancy.

PMID- 12521501
TI  - Review of eclampsia at the Nnamdi Azikiwe University teaching hospital, Nnewi
      (January 1996-December 2000).
AB  - In a retrospective study of 43 cases of eclampsia managed at the Nnamdi Azikiwe
      University Teaching Hospital Nnewi over a 5-year period, an incidence of 0.75%
      out of 5750 labour ward admissions was found. Eclampsia was more prevalent in the
      primigravidae (65%) and unbooked patients (83.7%) than in the multigravidae (35%)
      and booked (16.3%) patients. The mean age of the patients was 23.5 years. The
      majority of the eclamptic seizure (55.8%) occurred in the antepartum period. Many
      unbooked patients presented after more than two seizures. The most frequently
      used drugs in the management of eclampsia in the hospital were intravenous
      diazepam and hydralazine. For the 35 cases of antepartum eclampsia, 85.7% had a
      caesarean section while 14.3% had an operative vaginal delivery; none had a
      spontaneous vaginal delivery. There were four maternal deaths (9.3% of the cases)
      and seven perinatal deaths (16.3% of the cases). Clinical causes of death in the
      women were cardiopulmonary failure (three cases) and coagulation disorders (one
      case). The total maternal deaths in the hospital during this period was 19 given
      a maternal mortality rate of 330 per 100 000. Eclampsia, therefore, contributed
      21.1% of the maternal deaths. The role of health education and good antenatal,
      labour and early puerperal supervision is stressed in the reduction of the
      incidence of eclampsia in the developing countries.

PMID- 12521502
TI  - Vaginal breech delivery and perinatal mortality in twins.
AB  - An objective analysis of our clinical experience with the intrapartum management
      of twin gestations was undertaken in order to determine whether or not routine
      caesarean section is justified when the first twin presents by the breech. The
      perinatal mortality rate for breech first twins delivered vaginally was not
      statistically different from vertex presentations. There was no perinatal loss
      among babies delivered vaginally by the breech. There was no difference in
      perinatal outcome for the breech first twin born abdominally or vaginally. Our
      findings have allayed the fear that non-vertex vaginal delivery of the first or
      second twin is dangerous. We conclude that in the absence of a uterine scar or a
      footling presentation, there is no valid reason to prohibit vaginal delivery when
      either twin presents by the breech.

PMID- 12521503
TI  - Is propess a better method of induction of labour in nulliparous women.
AB  - Slow release prostaglandin pessary (propess) is compared with instant release
      prostaglandin gel (prostin) for the induction of labour in nulliparous women with
      a modified Bishop's score of less than 6. In this randomised study 50 women
      received prostin gel and 45 received propess. More than one dose of prostaglandin
      was required to achieve amniotomy more often in the propess group (53%) compared
      with the prostin group (34%) (P=0.03). Propess was unable to demonstrate any
      advantage over Prostin gel group. Propess was not cost-effective in this study.

PMID- 12521504
TI  - Toxoplasmosis and habitual abortion.
AB  - We set out to determine the role of toxoplasmosis, detected by serological tests,
      in habitual abortion. A total of 280 pregnant women aged 15-46 years with parity
      ranged from 0-9 were studied prospectively between January 2000 and May 2001 at
      King Hussein Medical Center. Analyses for IgG and IgM anti-toxoplasma were
      carried out using indirect fluorescent antibody assay (IFAT) and enzyme-linked
      immunosorbent assay (ELISA). Titres of the order of 1:16-1:2048 were considered
      positive. According to the results, women were divided into two groups;
      seropositive (n=132) and seronegative (n=148). One hundred and thirty-two (47.1%)
      pregnant women showed seropositivity to IgG anti-toxoplasma; of them, two (1.5%)
      developed IgM anti-toxoplasma during the second trimester. A statistically
      significant increase in the rate of seropositivity to toxoplasma with increasing
      age and parity was found (P<0.05). There was no significant difference in the
      rate of habitual abortion between seropositive and seronegative women. The
      seropositivity was higher among women living in rural areas (P<0.02), who are
      using rainwater to drink (P<0.02), ingesting undercooked meat (P<0.001) and who
      have contact with soil (P<0.02). Toxoplasma antibodies detected by positive
      serological tests tend to be higher with increased age and parity. It seems that
      they have no role in habitual abortion.

PMID- 12521505
TI  - Outcome of colposcopy in women presenting with postcoital bleeding and negative
      or no cytology--results of a 1-year audit.
AB  - We set out to identify histological abnormalities in women presenting with
      postcoital bleeding at the colposcopy clinic and the detection rate of
      abnormalities. This was a retrospective study based on the colposcopy clinic at
      Scunthorpe General Hospital. We investigated 45 patients with postcoital
      bleeding, 12 with negative referral smears and 33 with no referral smears. We
      found that 8.33% of patients with a negative referral smear had a histological
      abnormality. In patients with no referral smear the rate was 24.24%. The overall
      incidence of histological abnormality in the study group was 20% and of
      cytological abnormality 11.11%. Colposcopically directed biopsy is almost twice
      as effective as cytology in the detection of abnormality. Patients referred with
      negative cytology have a lower incidence of histological abnormality than those
      with no cytology. Women with postcoital bleeding should be seen in the colposcopy
      clinic.

PMID- 12521506
TI  - Knowledge, awareness and perception of sexually transmitted diseases (STDs) among
      Nigerian adolescent girls.
AB  - Knowledge, awareness and perception of STDs among 983 adolescent female high
      school students at Onitsha, Nigeria is analysed. There was good general awareness
      of the common STDs, HIV/AIDS: 93.6% (n=920), gonorrhoea: 76.3% (n=750); syphilis:
      69.1% (n=679), while the least was chlamydial disease: 6.6% (n=65). Knowledge of
      causes of STDs was high. Viruses were identified as the most common cause of STDs
      by 75.3% (n=740) of the respondents, followed by bacteria by 64.1% (n=630), while
      17.8% (n=175) of the students believed that poison/witchcraft caused STDs.
      Surprisingly, 35.5% (n=349) identified herbs and natural medicines as effective
      remedies for these STDs; 56.7% (n=557) identified antibiotics as treatment for
      STDs, 33.8% (n=331) antiviral drugs, while a high percentage of the students
      believed in prayer houses as a remedy: 30.3% (n=298). The most common source of
      information was through the school: 80.6% (n=792), followed by television: 80.1%
      (n=787); radio accounted for 73.1% (n=719) and health workers for 64.1% (n=630).
      Awareness about preventive measures was as follows: abstinence 67.4% (n=663),
      mutual fidelity 56.7% (n=557) and condoms 54.8% (n=539).

PMID- 12521507
TI  - HIV infection and sexual behaviour among infertile women in southeastern Nigeria.
AB  - This prospective study was carried out to estimate the prevalence of human
      immunodeficiency virus (HIV) infection and the risk factors for HIV infection in
      women undergoing laparoscopy evaluation for infertility. Of 1906 women evaluated
      between January 1995 and December 2000, 130 (6.82%) tested positive for HIV
      infection. Husbands of 58.5% of the HIV positive women also tested positive.
      Analysis of their sexual behaviour within the duration of the marriage revealed
      that the HIV positive infertile women had more sexual partners [86.2% (112/130)
      average of five partners vs. 38% (675/1776) average of two partners; P<0.001] and
      previous sexually transmitted infections [73.1% (95/130) vs. 56.8% (1009/1776);
      P<0.001] than the HIV negative infertile women. Previous history of induced
      abortion and blood transfusion was not significantly different for HIV positive
      and negative women (42.3% vs. 39.3%) and (1.5% vs. 1.0%), respectively, P>0.20.
      In conclusion, infertile women are exposed to a higher risk of HIV infection due
      to their promiscuous sexual behaviour in search of pregnancy.

PMID- 12521508
TI  - Contraceptive practice in a teaching hospital in south-east Nigeria.
AB  - During the study period of 31 months (1 November 1994-31 May 1997), the
      sociodemographic characteristics of 200 women attending the family planning
      clinic of Nnamdi Azikiwe University Teaching Hospital (NAUTH) Nnewi, South East
      Nigeria were studied. The peak age group of the family planning acceptors was 31
      35, constituting 82 (42%) of the study population. Women of parity 5-7
      constituted 99 (49.5%) of the study population; 66 (33%) women sought
      contraception less than 4 months after delivery and 120 (60%) within 1 year of
      delivery; 104 (52%) were still breastfeeding at time of visit; 120 (60%) had
      never used any form of contraception. The intrauterine contraceptive device was
      the most popular method, being chosen by 128 (64%) women, while only five (2.5%)
      women accepted bilateral tubal ligation. One hundred and eight (54%) women wanted
      more children in future. Most of the patients acquired knowledge of family
      planning through clinic personnel (nurses). The contraceptive prevalence rate in
      relation to deliveries at the hospital over the period of study was only 12.8%.
      There is a need for increased awareness on the availability and benefits of
      family planning on child spacing, family health and ultimately population control
      and society health.

PMID- 12521509
TI  - Hypersensitivity reactions in paclitaxel treatment of ovarian cancer patients.

PMID- 12521510
TI  - Experience of thermal balloon ablation in a district general hospital.

PMID- 12521511
TI  - Management of pregnancy complicated by maternal osteogenesis imperfecta. Report
      of a case with uterine rupture.

PMID- 12521512
TI  - Idiopathic uterine perforation in late pregnancy.

PMID- 12521513
TI  - Situs inversus with dextrocardia diagnosed in the third trimester.

PMID- 12521514
TI  - Idiopathic thrombocytopenic purpura treated with pulsed high dose
      methylprednisolone followed by platelet transfusion.

PMID- 12521515
TI  - Ultrasound diagnosed abdominal pregnancy at 34 weeks' gestation.

PMID- 12521516
TI  - Transplacental flecainide therapy in the treatment of fetal supraventricular
      tachycardia.

PMID- 12521517
TI  - Isolated menses: a benign, self-limited process.

PMID- 12521518
TI  - Recurrence of cutaneous malignant melanoma at 24 years, mimicking ovarian
      malignancy.

PMID- 12521519
TI  - Chronic vaginal discharge secondary to a hydrosalpinx.

PMID- 12521520
TI  - Expulsion of the fetus into the broad ligament as a complication of midtrimester
      termination of pregnancy.

PMID- 12521521
TI  - Vaginal atresia treated successfully with vaginal dilators.

PMID- 12521522
TI  - Isthmic stenosis following radical trachelectomy.

PMID- 12521523
TI  - Psammoma bodies on postmenopausal cervical smear--a rare sinister finding.

PMID- 12521524
TI  - Exceptionally high levels of CA125 due to endometriosis.

PMID- 12521525
TI  - Selective transvaginal embryo reduction in heterotopic pregnancy located intra
      abdominally.

PMID- 12521526
TI  - Munchausen's syndrome with predilection [correction of predeliction] for
      gynaecology.

PMID- 12521527
TI  - Metastatic carcinoma of breast diagnosed following hysteroscopy and endometrial
      biopsy.

PMID- 12521528
TI  - Characteristics of magnetic resonance imaging findings of ovarian adult granulosa
      cell tumour.

PMID- 12521529
TI  - The analyst at work. Nina.

PMID- 12521530
TI  - Response to Annie Anargyros-Klinger's 'Depression and Leo Tolstoy'.

PMID- 12521531
TI  - The trajectory of psychoanalysis: a prognostication.
AB  - I present an overview of the development to this point of psychoanalysis as a
      discipline--both as a theory of the mind and a treatment of the disorders of the
      mind--and offer a prediction concerning evolving development over its (near)
      future. My focus is on the coherence of psychoanalysis as a theoretical
      structure, starting with Freud's strenuous endeavours to maintain the
      psychoanalysis that he had single-handedly created as a unitary and unified
      theory, tracing then the breakdown of this effort, even in Freud's lifetime, into
      the burgeoning theoretical diversity or pluralism that characterises worldwide
      psychoanalysis today, and then going on to the beginning appearance of evidences-
      not yet widely remarked--of growing convergences from within very disparate and
      even seemingly very opposed theoretical perspectives, at least at the level of
      technical interventions and experience-near clinical theory, with implications,
      however, even for the level of experience-distant general (metapsychological)
      theory. Such a development, if sustained, as I anticipate, would strengthen the
      credibility of psychoanalysis as a science of the mind, amenable to growth
      through empirical research in accord with the canons of scientific method.

PMID- 12521532
TI  - Why aggression? Metapsychological, clinical and technical considerations.
AB  - On the basis of a formalised view of metapsychology, the author briefly considers
      the problems inherent in the Freudian notion of a death drive or aggressive drive
      and then goes on to develop a new theoretical conception of aggression.
      Aggression is understood as an affect, action or affective action and, in
      relation to these, as an expression of the intensity with which a drive--whether
      it be the sexual drive with its libidinal cathexes or the self-preservative drive
      with its lethic cathexes--seeks to attain its object. In this context the author
      regards the regulation of closeness and distance with respect to the
      'psychogeometric locus' of the relevant drive object as being of central
      importance. She contends that neurotic personalities suffer from specific
      distortions in the perception of the psychogeometric locus of their drive
      objects, which may give rise to an intensification of the drive tendencies
      prevailing in these individuals at any given time so that these tendencies take
      on an aggressive character. The author presents two clinical vignettes to show
      how her approach allows aggression and its occurrence to be conceptualised
      without resorting to the idea of a primary aggressive drive, and draws attention
      to the resulting technical consequences for interpretation.

PMID- 12521533
TI  - The exclusion of the other. A clinical contribution to an object-relations theory
      of obsessional defence.
AB  - The author begins by noting that the subject of obsessions and obsessional
      neurosis seems to have fallen out of favour with the analytic community in spite
      of the important part it played in the formation of Freud's theories, and
      notwithstanding the significance of its mechanisms in the maturation of the ego.
      He then discusses some theoretical considerations regarding the development of
      the taboo on touching and, by extension, contact. Attention is drawn to the
      parallels with autistic functioning emphasised by other authors. Particular
      importance is attached to the distinction between internal and external reality
      that arises during the anal-sadistic phase and that leads to polarisation and
      splitting in obsessional neurosis. Following a discussion of the transference
      countertransference situation with obsessional patients and of their concretistic
      experience in the treatment situation, as also featured in the literature, an
      extensive case history exemplifies the author's contentions and shows how the
      patient concerned developed during the course of his analysis. After pointing out
      the importance of the avoidance of identifications as a mechanism of obsessional
      defence, the author concludes the paper with a brief comparison of obsessional
      and hysteriform functioning and a characterisation of the obsessional defence as
      the excessive recourse to perverted thought functions so as to ward off paranoid
      anxieties.

PMID- 12521534
TI  - The repressed and implicit knowledge.
AB  - The distinction between implicit (non-conscious) and explicit (conscious)
      knowledge made by cognitive scientists is applied to the psychoanalytic idea of
      repressed contents. The consequences of repression are suggested to have been
      caused by implicit representations. Repressed memories can also be treated in
      terms of explicit representations, which are prevented from becoming activated.
      Implicit knowledge cannot, however, be made conscious, and thus the idea of
      becoming conscious of the repressed desires and fears that have never been
      conscious is contradictory. This tension may be relieved by reconceptualising the
      idea of becoming conscious of the repressed. It is suggested that this could be
      seen as creating explicit knowledge about the effects of implicit
      representations. By applying the implicit/explicit knowledge distinction,
      psychoanalytic ideas concerning the repressed could be connected to current views
      in the domain of cognitive orientation.

PMID- 12521535
TI  - Perverse thought.
AB  - Based on Bion's work on the 'psychotic and non-psychotic parts of the
      personality', the author hypothesises the existence of a special type of thought
      disorder known as 'perverse thought'. First the author presents an overview of
      the major contributions to the concept of perversion that have a bearing on
      'perverse thought'. These include Freud's splitting and disavowal concepts,
      Klein's projective identification concept, Bion's -K link and Meltzer's
      transference perversion. Then, by means of a case study and some vignettes, the
      author illustrates how this thought disorder is configured within the analytic
      process. The author focuses on three main aspects of this pathology: the specific
      modality of projective identification in a perverse scheme, the lie and some
      important clinical events that reveal an attack against knowledge through the
      formation of the -K link. Perverse thought is an important resistance mechanism
      in the analytic process. Its clarification is essential, given that its main
      objective is to attack the knowledge process, and therefore truth, in order to
      pervert the analytic relationship.

PMID- 12521536
TI  - 'Actual neurosis' and psychosomatic medicine: the vicissitudes of an enigmatic
      concept.
AB  - Out of the concept of neurasthenia, the main non-psychotic diagnosis of
      nineteenth-century psychiatry besides hysteria, and on the basis of
      psychophysiological problems of his own, self-diagnosed as neurasthenia, Freud
      developed the notion of 'actual neurosis', a 'contentless psychic state'
      manifested by various somatic symptoms and a depressive mood, which he attributed
      to a chemical factor associated with aberrant sexual practices and in particular
      masturbation. Rejected by post-Freudian analysts as such along with the diagnosis
      of neurasthenia, the concept of 'actual neurosis' has survived under various
      theoretical schemes that seek to explain psychosomatic illness and somatisation,
      in general, with its concomitant poverty of affects and dearth of fantasy life.
      In more recent years, the concept of 'actual neurosis' has resurfaced under the
      label of chronic fatigue syndrome, a medical entity thought to be an
      immunological deficiency, while in psychoanalysis Freud's idea of a contentless
      mental state has been replaced by that of unconscious fantasy and symbolisation
      at a pre-genital or pre-verbal level.

PMID- 12521537
TI  - Freud's 'problem': cognitive neuroscience & psychoanalysis working together on
      memory.
AB  - The first part of this paper discusses the development of Freud's views on memory
      from the time of the Project up to the formulation of the second topography.
      Freud's attempts to match his psychological views with an organic model were
      necessarily inconclusive, but in the process many innovative ideas about memory
      can be seen to resonate with recent developments in cognitive neuroscience. A
      brief discussion of perceptual identity, internal perception and Freud's affect
      theory introduce the central theoretical idea in the second half of the paper,
      namely that Identification can be seen as a form of memory. Modern memory theory
      is linked with the superego, following which the author proposes that internal
      objects might be renamed 'memory-objects' and that these can be understood in
      terms of the distinction made in cognitive neuroscience between implicit and
      explicit memory and between different parts of the brain, in particular the
      amygdala, the basal ganglia and the hippocampus. Klein's 'memory in feeling' and
      the views of Fairbairn and Ogden in relation to the dynamic nature of internal
      objects are briefly discussed. The paper ends with a few comments on the
      aberrations of memory and some implications of the implicit memory-object system.

PMID- 12521538
TI  - The didactics of psychoanalytic education.
AB  - The author first discusses general didactic considerations regarding
      psychoanalytic education and the teacher-pupil relationship. He then demonstrates
      that psychoanalytic education is greatly influenced by the ideal of a liberal
      education, of which in Germany there is a strong tradition under the name
      'Bildung'. The main characteristics of 'Bildung'--as opposed to professional
      training--are that the objectives remain undefined and there is no attempt to
      achieve defined and operationalisable professional qualifications. The
      relationship between teacher and pupil is characterised by authority and trust. A
      psychoanalytic education by means of a 'liberal education' is based upon the
      assumption that the student should be motivated and supported in achieving
      competence through a passionate study of the world of psychic reality. Today,
      however, psychoanalytic education must be seen within a contemporary context that
      forces us to abandon the ideals of a liberal education, to operationalise the
      subjects studied and to control the education itself with regard to efficiency
      and results. These modern demands are the result of a professionalisation which
      has reached all social professions and from which psychoanalysis also cannot
      escape. Because of this, it is especially important to reflect on our educational
      methods and objectives. The author makes several suggestions on this subject. It
      is to be hoped that psychoanalysis will find its own way, without, on the one
      hand, losing sight of the special nature of psychoanalytic competence through an
      over-hasty adaptation to the process of professionalisation and, on the other
      hand, without reverting to unquestioned and outdated ideas on education.

PMID- 12521539
TI  - Organisational and educational internal impediments of psychoanalysis:
      contemporary challenges.
AB  - Our psychoanalytic discipline originated, has evolved and is still located within
      a congregational network that blends and binds together, in an inextricable and
      contradictory way, the missionary mandates and commendations of a 'movement' and
      a 'cause' with the inherent prerogatives and functions of academic professions
      and sciences. In this paper the author explores the consequential past and
      present impedimenta of this organisational and educational syncretism, for six
      fundamental dimensions of action for psychoanalysis. Subsequently, the nature of
      a proposition is delineated, suggesting a reorganisation, local and
      international, to address what the author visualises as five of our most pressing
      contemporary challenges: a) an autonomous university educational model, freed
      from regressive societal-political inertias, enabling us to abandon our seclusive
      monasticism; b) the consolidation of an epistemological frame of reference,
      idiographic and nomothetically substantiated against our cumulative inductivism,
      which is the seedbed of our sectarianism, cross-sterilisation and pseudo
      ecumenism; c) local and external educational and professional systems of
      accreditation and certification, independent from affiliation and membership
      privileges of our supraordinate ecclesia; d) social relevance and community
      presence, moving away from our meaningless organisational and educational
      cloistering; and e) a local and international functional and interdependent
      reorganisation, in the context of sovereignty and integrity, in contrast to our
      prevalently crusading and indoctrinating homogamous pathological co-dependency.
      The author concludes that only a harmonisation of objectives and administrative
      structure might loosen the talons of faith that keep us retrogressively tied to
      our past.

PMID- 12521540
TI  - On Abraham's 'The psychodynamics of orgasm'.

PMID- 12521541
TI  - Comments on the case of Nina.

PMID- 12521542
TI  - Speech events, language development and the clinical situation.
AB  - Psychoanalysis brings about psychic change by the mediation of speech. This paper
      reflects upon the significance of the structure and developmental organisation of
      the speech event as a verbal and non-verbal unit composed of semantically and
      prosodically encoded messages, interactions and emotional contact between
      partners. Spoken words communicate semantic meanings and the affects of a given
      speech event. Words carry personal emotional meanings which are inseparable from
      their referential significance. Such emotional meanings are very hard to
      articulate in words. They are conveyed by the ineffable but essential feelings
      present in their sound and pronunciation. Speech is an intentionally object
      related and emotionally engaging social activity resulting from a child having
      been spoken to early in life by an adult wanting to establish affective verbal
      contact. The early organisation and later transformation of the structure of the
      speech event carries private meanings for each person's listening and speaking
      stance. A refined understanding of the structural and emotional complexities of
      verbal communicative exchanges during analysis may enhance the analyst's ability
      to understand the patient's manner of participation in the analytic process.

PMID- 12521543
TI  - Adjuvant radiotherapy in patients undergoing surgical treatment for cervical
      cancer or endometrial carcinoma.

PMID- 12521545
TI  - Fatigue and gynecologic cancer.
AB  - Fatigue is common in women with gynecologic cancers and is thought to be
      multifactorial. Anemia, cachexia, pain, and depression are frequently associated
      with cancer and treatment-related fatigue and should be evaluated and treated.
      The National Comprehensive Cancer Network Fatigue Practice Guidelines are helpful
      in the assessment and treatment of women with gynecologic cancer-related fatigue.

PMID- 12521546
TI  - Sentinel node techniques in cancer of the vulva.
AB  - The sentinel lymph node procedure, with the combined technique (preoperative
      lymphoscintigraphy with (99m)Technetium-labeled Nanocolloid and Patente Blue V ),
      is a promising staging technique for patients with vulvar cancer. The clinical
      implementation of the sentinel lymph node procedure and the role of additional
      histopathologic techniques of the sentinel lymph nodes are under investigation.

PMID- 12521547
TI  - Ovarian cancer associated with inherited mutations in BRCA1 or BRCA2.
AB  - Most hereditary ovarian cancers are associated with germline mutations in the
      BRCA1 or BRCA2 genes. These genes are involved in many vital cellular functions,
      including DNA damage recognition, DNA repair, and control of transcription.
      Prophylactic oophorectomy is the most effective method of reducing ovarian cancer
      risk in women known to carry BRCA1 or BRCA2 mutations. Women with BRCA1
      associated ovarian cancers seem to have a somewhat better survival than women
      with sporadic ovarian cancer. Loss of BRCA1 function may impact response to
      chemotherapy via effects on DNA damage response. Research priorities include
      designing functional tests for BRCA1 and BRCA2, understanding the impact of BRCA1
      and BRCA2 mutations on response to specific cancer therapies, and development of
      innovative cancer prevention strategies in women with BRCA1 and BRCA2 mutations.

PMID- 12521548
TI  - Therapy for recurrent ovarian cancer.
AB  - Primary treatment of advanced ovarian cancer is well established. The combination
      of tumor debulking and platinum/taxane polychemotherapy has led to improved
      treatment results in recent years. However, most patients with ovarian cancer
      will relapse, rendering treatment of recurrent ovarian cancer of great clinical
      interest. Relapse therapy should depend on the treatment-free interval. Patients
      with progressive disease during primary treatment or cancer relapse within 6
      months after the completion of primary treatment are platinum refractory, and,
      therefore, prognostically unfavorable. For these patients with poor outcome,
      quality of life should be predominantly considered before initiation of
      treatment. Cancer relapse after an interval of more than 6 months after the
      completion of primary treatment cannot be cured; however, platinum-based
      chemotherapy, in individual cases combined with secondary tumor debulking, can
      lead to persisting remissions.

PMID- 12521549
TI  - Surgery for elderly patients with ovarian cancer.
AB  - The stage and tumor remnants after radical surgery are the most important
      prognostic factors in patients with ovarian cancer. Because the incidence of
      ovarian cancer is highest in elderly women, and mostly advanced stages occur,
      radical surgery is necessary in this population as well as in younger patients.
      Age and the surgeon's expertise are the factors that influence the quality of
      surgical treatment of ovarian cancer. Surgical treatment of ovarian cancer should
      therefore be confined to centers with the required infrastructure and expertise.

PMID- 12521552
TI  - Fetal cells in maternal blood.
AB  - Fetal cells in maternal blood represent the future of prenatal screening and
      diagnosis. The possibility of analyzing fetal cells recovered from maternal blood
      could provide screening and diagnostic protocols characterized by high
      sensitivity and specificity with no direct risk to the developing fetus. Years of
      investigation have thus far not led to the development of reliable and consistent
      protocols; nonetheless, fetal cell recovery promises to be an attractive addition
      to noninvasive prenatal diagnosis.

PMID- 12521554
TI  - Arthroscopic surgery for arthritis of the knee.

PMID- 12521553
TI  - Pharmacologic methods for cervical ripening and labor induction.
AB  - Evidence from the obstetric literature suggests that the frequency of labor
      induction is increasing. According to the National Center for Health Statistics,
      the rate of labor induction has more than doubled during the past 10 years: from
      9% in 1989 to 19.9% in 2000. As labor induction has become more widely used in
      recent years, the number of medications used for preinduction cervical ripening
      has expanded greatly. In this article, we review the evidence-based literature
      assessing the safety and efficacy of the most common cervical ripening and labor
      induction agents.

PMID- 12521555
TI  - Understanding and managing the back pain of pregnancy.
AB  - Approximately 50% of all pregnant women experience back pain during pregnancy.
      The causes and risk factors associated with the back pain encountered during
      pregnancy continue to be evaluated. The key to evaluating and managing these
      patients is the history and physical examination. Recognizing characteristics of
      the frequently encountered back pain of pregnancy as well as uncommon sources of
      back pain during pregnancy is essential in establishing an accurate diagnosis and
      initiating prompt and effective management.

PMID- 12521556
TI  - Percutaneous treatment of osteoporotic spinal compression fractures.
AB  - Osteoporotic spinal compression fractures are a significant health risk for
      elderly females, as well as other patient groups. These fractures are associated
      with an increased risk of mortality in comparison with age-matched controls.
      Recent techniques of minimally invasive surgical treatment show promising early
      results with respect to pain reduction and restoration of function, with low
      procedural complication rates.

PMID- 12521557
TI  - Hip fractures in the elderly.
AB  - The incidence of hip fractures in the elderly is increasing worldwide, with
      650,000 fractures expected in the United States by the year 2050. The mechanism
      of injury is typically a ground-level fall. Efforts at prevention focus on
      reducing risk factors by aggressive medical management of comorbidities, use of
      protective garments, and modification of the individual's environment to lessen
      the chance of falling. Treatment is associated with an elevated mortality rate
      and compromised functional outcome.

PMID- 12521558
TI  - Anterior knee pain: symptom or syndrome?
AB  - A chief complaint for many patients is anterior knee pain. This is more common in
      females; the incidence is two to three times than that in males. The challenge
      for the physician is to determine the etiology, the diagnosis, and the best
      treatment. The goal of this article is to provide key elements of the history,
      physical examination, and treatment options to help assist in the management of
      patients with anterior knee pain or patellofemoral pain syndrome.

PMID- 12521559
TI  - Cerebral Toxoplasmosis.
AB  - The choice of drugs for treating cerebral toxoplasmosis is limited. There are
      only three drugs available, and, of these, pyrimethamine and sulfonamide are
      invariably used in combination. Clindamycin is an alternative choice. Another
      drug, spiramycin, has poor central nervous system penetration, but achieves high
      concentrations in the placenta, and it is useful for treatment of toxoplasmosis
      during pregnancy. Because long-term maintenance therapy is often necessary,
      particularly in patients with AIDS, a wider choice of antibiotics is urgently
      necessary, because of potential problems with drug resistance and side effects.
      Treatment may be started empirically in any patient with HIV infection and
      multiple brain lesions. The drugs of choice are a combination of sulfadiazine and
      pyrimethamine. Folinic acid should be added to prevent pyrimethamine-induced bone
      marrow suppression. Repeated neuroimaging, 2 weeks after initiating therapy, is
      needed to assess efficacy of treatment. If CD4 cell counts remain below 100 cells
      per mm(3), lifelong therapy is needed. Tissue diagnosis should be established in
      patients who do not respond to treatment, who have solitary lesions, or in
      patients without AIDS. Recent breakthroughs in the understanding of the biology
      of Toxoplasma will result in the development of a range of new therapies in the
      near future.

PMID- 12521560
TI  - Subdural Empyema.
AB  - Subdural empyema represents loculated infection between the outermost layer of
      the meninges, the dura, and the arachnoid. The empyema may develop intracranially
      or in the spinal canal. Intracranial subdural empyema is most frequently a
      complication of sinusitis or, less frequently, otitis or neurosurgical
      procedures. Spinal subdural empyema is rare and may result from hematogenous
      infection or spread of infection from osteomyelitis. The most common organisms in
      intracranial subdural empyema are anaerobic and microaerophilic streptococci, in
      particular those of the Streptococcus milleri group (S. milleri and Streptococcus
      anginosus). Staphylococcus aureus is present in a minority of cases, and multiple
      additional organisms, including Gram-negative organisms, such as Escherichia
      coli, and anaerobic organisms, such as Bacteroides, may be present. Pseudomonas
      aeruginosa or Staphylococcus epidermidis may be present in cases related to
      neurosurgical procedures, and Salmonella species have been detected in patients
      with advanced AIDS; multiple organisms may be present simultaneously. Spinal
      subdural empyemas are almost invariably caused by streptococci or by S. aureus.
      Subdural empyema--whether it occurs in the skull or the spinal canal--may cause
      rapid compression of the brain or spinal cord, and represents an extreme medical
      and neurosurgical emergency. The diagnostic procedure of choice for intracranial
      and spinal subdural empyema is MRI with gadolinium enhancement. Computed
      tomography scan may miss intracranial subdural empyemas detectable by MRI.
      Conversely, occasion spinal subdural empyemas may be detected by CT myelography
      where MRI is negative. Treatment in virtually all cases of intracranial or spinal
      subdural empyema requires prompt surgical drainage and antibiotic therapy. Pus
      from the empyema should always be sent for anaerobic, as well as aerobic,
      culture. Because intracranial subdural empyemas may contain multiple organisms,
      provisional antibiotic therapy of intracranial subdural empyema, where the
      organism is unknown, should be directed against S. aureus, microaerophilic and
      anaerobic streptococci, and Gram-negative organisms. Antibiotics should include
      1) nafcillin, oxacillin, or vancomycin; plus 2) a third generation cephalosporin;
      plus 3) metronidazole. Provisional antibiotic therapy of spinal subdural empyemas
      should be directed against S. aureus and streptococci, and should include
      nafcillin, oxacillin, or vancomycin. Morbidity and mortality in intracranial and
      spinal subdural empyema relate directly to the delay in institution of therapy.
      Both conditions should, thus, be treated with great urgency.

PMID- 12521561
TI  - Botulism.
AB  - Botulinum toxin is the most potent toxin known to humans and as little as 100 ng
      can be lethal. The toxin blocks peripheral cholinergic neurotransmission at the
      neuromuscular junction and cholinergic autonomic nervous system by introducing an
      endopeptadase enzyme into the presynaptic side of the synapse. The endopeptadase
      cleaves acetylcholine vesicle docking proteins that are required for the synapse
      to release acetylcholine into the synaptic cleft. Botulism occurs from
      consumption or inhalation of preformed botulinum toxin or growth of Clostridium
      botulinum bacteria in the infant gastrointestinal tract or within a wound. Growth
      of C. botulinum in the immature gut or wound will release botulinum toxin that
      reaches the circulation. All forms of botulism cause progressive weakness, bulbar
      signs (blurred vision, diplopia, mydriasis, dysphagia, and dysarthria), and
      respiratory failure with normal sensation and mentation. Treatment is aimed at 1)
      maintaining respiration via intubation and mechanical ventilation, 2) stopping
      progression of weakness by administration of botulinum antitoxin (equine
      trivalent botulinum antitoxin for adults and botulism immune-globulin intravenous
      human for infant botulism), and 3) preventing complications from weeks of
      paralysis with good supportive care. The source of the botulinum toxin should be
      identified to prevent additional cases. Patients can recover normal muscle
      strength within weeks to months, but usually complain of fatigue for years.

PMID- 12521562
TI  - Disease-modifying Therapies for Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is likely an autoimmune disorder, although this remains
      unproven. Immunotherapeutic treatments have been shown to be helpful, especially
      in relapsing forms of the illness, but the treatments are incomplete, and many
      patients continue to worsen over time, even with standard therapy.
      Immunotherapies presently available appear to have their greatest effect when
      used early in the course of the illness. In relapsing-remitting multiple
      sclerosis (RRMS), there is overwhelming Class I data from large clinical trials
      that supports the use of interferon-beta-1a (IFNbeta-1a), interferon-beta-1b
      (IFNbeta-1b), and glatiramer acetate. Comparative data are limited, and results
      published in different trials support the idea that treatment outcomes with the
      various drugs are more similar than different. Decisions about treatment choice
      should be tailored to the needs of the individual patient. With the exception of
      a small number of patients with benign MS, all RRMS patients should be treated
      with one of the interferons or glatiramer acetate. There are Class I data
      consistent with the idea that higher dose or more frequent administration of
      interferon-beta (IFNbeta) is associated with better clinical outcome and reduced
      progression of changes on brain MRI scans. The duration of this effect is not
      clear, and higher dose with more frequent administration is associated with
      higher cost, more side effects, and greater production of interferon antibodies.
      Interferon antibodies possibly reduce efficacy of IFNbeta in RRMS and secondary
      progressive multiple sclerosis (SPMS). Clinically isolated syndromes (CIS) of
      demyelination in the central nervous system can be reliably diagnosed, and the
      risk of further episodes of demyelination is consistent with the diagnosis of
      RRMS stratified by use of brain MRI scans. Patients at high risk of developing
      RRMS after CIS achieve significant benefit after treatment with IFNbeta-1a, and
      initiation of therapy after CIS should be given strong consideration. There are
      no similar data for IFNbeta-1b or glatiramer acetate, but logic would dictate a
      similar response with these agents. In SPMS, there are Class I data that
      treatment with IFNbeta-1a or IFNbeta-1b has a significant effect on progression
      of brain MRI lesions, but clinical outcomes are less clearly affected. It is
      justifiable to treat SPMS patients with IFNbeta. Mitoxantrone may be effective in
      slowing progression of SPMS, and its risks are moderate. It should be used in
      patients with SPMS, but potential long-term risks must be discussed with the
      patient in detail. Results of treatment of SPMS in advanced cases (Extended
      Disability Status Score greater than 6.5, or restricted to wheelchair) is mostly
      unknown. These patients are at high risk of developing infections, especially if
      they use indwelling catheters, and the use of agents that induce
      immunosuppression may be risky. There are no effective therapies for primary
      progressive multiple sclerosis (PPMS). Although PPMS patients are frequently
      treated with one or more therapeutic agents, there is no medical justification
      for this now.

PMID- 12521563
TI  - Current Complementary and Alternative Therapies for Multiple Sclerosis.
AB  - The use of complementary and alternative medicine (CAM) appears to be high in the
      general population and in patients with multiple sclerosis (MS). There are no
      diets or dietary supplements that are definitely effective in altering the
      disease course in MS. However, diets and dietary supplements that increase the
      intake of polyunsaturated fatty acids may produce mildly beneficial effects.
      Because these approaches are not definitely effective, they may be of limited
      interest to physicians and other conventional health providers. In contrast, for
      patients with MS, these interventions may be of considerable interest, because
      they may be mildly effective and are inexpensive and relatively safe. Vitamin D,
      ginkgo biloba, cannabinoids, and Padma 28 produce immunomodulatory actions and
      therapeutic effects in experimental autoimmune encephalomyelitis. However, for
      these compounds, there are not enough clinical trial data or safety information
      to support their use as disease-modifying therapies. The role of antioxidant
      compounds in MS is unclear. There is no evidence that vitamin B(12)
      supplementation or gluten-free diets are effective MS therapies. Conventional
      health providers can play an important role in the care of MS patients by being
      open to discuss CAM therapies and by providing objective MS-relevant CAM
      information.

PMID- 12521564
TI  - Current Therapies for Paraneoplastic Neurologic Syndromes.
AB  - Paraneoplastic neurologic syndromes (PNS) comprise an extensive group of
      heterogeneous disorders that can affect any part of the central and peripheral
      nervous system. There is evidence that many of these disorders are mediated by
      immunologic responses triggered by the presence of a cancer. Several immunologic
      mechanisms and many antigenic targets have been related to these disorders. Some
      disorders of the neuromuscular junction or peripheral nervous system are directly
      mediated by antibodies, and they may have a paraneoplastic origin or develop
      without a tumor association. For these disorders and a few PNS of the central
      nervous system, immunotherapy may result in neurologic improvement. However, for
      most PNS of the peripheral and central nervous system the response to any type of
      therapy is, in general, disappointing. The main concern of the clinician should
      be to rule out other diagnostic entities and to uncover the presence of the
      associated neoplasm that often remains elusive to detection. In general, the best
      approach to treat PNS is to discover and treat the tumor promptly, and provide
      supportive care for the neurologic deficits with symptomatic treatment and
      physical therapy. In a few cases, depending on the syndrome and if the patient is
      in the early stages of the neurologic disease, treatment with immunosuppression
      may have some effect on the PNS.

PMID- 12521565
TI  - Stiff-person Syndrome.
AB  - Stiff-person syndrome (SPS) is a progressive neurologic disorder characterized by
      1) stiffness that is prominent in axial muscles, with co-contraction of agonist
      and antagonist muscles; 2) sudden episodic spasms; and 3) absence of another
      disease that causes similar symptoms. The diagnosis of SPS is based on clinical
      grounds and requires a high degree of suspicion. The diagnosis is, however, aided
      by electromyography, which demonstrates motor unit firing at rest simultaneously
      from the agonist and antagonist muscles, and by high serum titers of antibodies
      against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the
      synthesis of gamma-aminobutyric acid (GABA), which is the brain's main inhibitory
      neurotransmitter. The reduced GABA level in the brain and cerebrospinal fluid
      explains the patients' stiffness and justifies the clinical improvement observed
      by drugs enhancing GABAergic transmission. The association of SPS with other
      autoimmune disorders or autoantibodies, the intrathecal GAD-specific
      immunoglobulin G antibody synthesis, and the suppression of GABA by the patient's
      antibodies supports the autoimmune nature of SPS and justifies the use of
      immunotherapies. At present, GABA-enhancing agents, such as benzodiazepines,
      valproate, vigabatrin, tiagabine, gabapentin, and baclofen, provide symptomatic
      relief. Plasmapheresis, steroids, and periodic intravenous immunoglobulin
      infusions provide additional and lasting benefit. In this article, the treatment
      options for patients with SPS are discussed based on the authors' experience and
      that of others. The beneficial effects from the first controlled study conducted
      in SPS using intravenous immunoglobulin are presented.

PMID- 12521566
TI  - Small Bowel Diverticulosis: An Overlooked Entity.
AB  - Small bowel diverticulosis (SBD) is a rare entity. Most cases of diverticulosis
      are asymptomatic. SBD is often discovered incidentally during contrast studies
      and endoscopy. When patients report chronic gastrointestinal symptoms such as
      abdominal pain, bloating, flatulence, and anemia, SBD is often an overlooked
      diagnosis. Patients requiring treatment for SBD are those with complications such
      as malabsorption, hemorrhage, obstruction, and acute inflammation with abscess or
      rarely perforation. Malabsorption can be managed with broad-spectrum antibiotics
      and vitamin supplementation. Hemorrhage is treated conservatively with
      resuscitation efforts, but recurrent bleeding requires surgery. Enteroliths
      causing obstruction in the duodenum can be relieved by endoscopy, that is, by
      manipulation, but jejunoileal obstruction requires a resection. Pseudo-
      obstruction may be managed with prokinetics such as metoclopramide, erythromycin,
      and the 5-hydroxytryptamine 4 agonist tegaserod. Uncomplicated cases of SBD are
      treated with bowel rest and antibiotics. However, perforation or abscess
      formation not amenable to percutaneous drainage mandates surgical resection. Any
      patient with a triad of anemia, abdominal pain, and an abdominal radiograph with
      dilated loops of small bowel merits SBD in the differential diagnosis.

PMID- 12521567
TI  - Current Insights in Whipple's Disease.
AB  - Therapy for Whipple's disease should be continued for a minimum of 1 year, and
      the regimen should include an agent or agents that achieve acceptable
      concentrations in the central nervous system, given the likelihood of recurrence
      at this site. Clinical follow-up of proven cases of Whipple's disease should be
      conducted for a minimum of 10 years after discontinuation of therapy, given the
      potential for late relapses. Polymerase chain reaction analysis is preferred
      rather than endoscopy when evaluating for disease recurrence.

PMID- 12521568
TI  - Gastrointestinal Amyloidosis: Approach to Treatment.
AB  - The main treatment goals in amyloidosis are twofold: 1) to diagnose the
      underlying disease state accurately to guide effective primary therapy (if
      available) and 2) to ameliorate symptoms. The correct diagnosis is essential
      because disease-modifying therapies vary widely according to the underlying
      primary pathology. Primary treatment options remain limited. The best evidence is
      for high-dose chemotherapy, followed by autologous stem cell transplantation in
      patients with primary systemic amyloidosis. High-flux hemodialysis (HD) may
      prevent HD-related amyloidosis. Liver transplantation may be an option for
      patients with familial amyloidotic polyneuropathy. Several novel specific
      therapies are under investigation, including small molecule drugs and vaccines.
      Their efficacy and safety in humans remain to be demonstrated. In the absence of
      specific cures, symptom-directed therapy assumes a paramount role and can improve
      quality of life by mitigating diarrhea or pain, for example.

PMID- 12521569
TI  - Small Bowel Lymphoma.
AB  - Treatment of small bowel lymphoma requires the expertise of medical and surgical
      subspecialists. The two most important factors that determine the optimal
      treatment are histology and staging of small bowel lymphoma. Other factors that
      may affect treatment include age, multiple areas of involvement, tumor size, and
      perforation. At present, the best treatment for gastrointestinal lymphoma (stage
      IE disease) is limited resection of the tumor, followed by postoperative
      radiotherapy. The cure rate is approximately 75% for stage IE patients, even for
      those with aggressive histologic types. Chemotherapy is reserved for advanced
      staged tumors. In patients with regional nodal involvement or extranodal
      involvement confined to one side of the diaphragm (pathologic stage IIE disease),
      chemotherapy should be combined with radiation therapy. The best chemotherapy
      regimen depends on the histology of the tumor. For diffuse large B-cell lymphoma,
      the most frequently diagnosed subtype of non-Hodgkin's lymphoma (NHL), the CHOP
      regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is still the
      gold standard. Clinical trials have been conducted evaluating the new monoclonal
      antibody rituximab, along with the CHOP regimen for primary NHL. Results have
      been promising. The use of rituximab in the treatment of extranodal lymphoma is
      still being evaluated. Low-grade lymphomas have a more indolent course and do not
      respond as well to combination chemotherapy agents as the high-grade tumors.
      Fludarabine alone or in combination with cyclophosphamide is effective as a first
      line agent for patients with low-grade NHL. It has also been used to treat
      relapsed or refractory low-grade NHL. Some promising results have been reported
      using the chemoimmunotherapy agent rituximab alone or in combination with
      fludarabine for the treatment of low-grade NHL. However, clinical trials are
      still needed. In patients with nodal involvement on both sides of the diaphragm
      or other extranodal involvement such as bone marrow or liver (pathologic stages
      IIIE and IVE), the disease is managed primarily with combination chemotherapy.
      Radiation therapy is reserved for treatment of initially bulky tumor sites,
      treatment of residual disease following chemotherapy, or serious local problems.
      The disease can be controlled in 25% to 40% of patients with stage IIIE or IVE
      disease. As with stage IIE disease, the optimal chemotherapy regimen depends on
      the histologic subtype of NHL.

PMID- 12521570
TI  - Systemic Mastocytosis.
AB  - Systemic mastocytosis is a rare clinical disorder characterized by the
      proliferation of mast cells, which are commonly in the skin but may be found in
      other body sites as well. Mast cells contain chemically active substances that,
      on release, produce symptoms associated with the disease. The intent of this
      review is to provide some insight into the clinical nature of this disorder.

PMID- 12521571
TI  - Gastroesophageal Reflux Disease.
AB  - Lifestyle modifications should be discussed with every patient with symptoms of
      chronic gastroesophageal reflux disease (GERD). Proton pump inhibitors are the
      most efficacious medical therapy for GERD. H(2) receptor antagonists are likely
      to be effective in patients with mild to moderate GERD and for occasional
      symptoms. Promotility drugs have limited efficacy and produce frequent side
      effects. Surgery is a reasonable option for chronic management. Endoscopic
      therapy remains experimental until more long-term results are available.

PMID- 12521572
TI  - Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis is a disease that has moved from relative obscurity,
      known to a few pediatricians, to one of emerging interest and attention in both
      the pediatric and adult literature. In part, this is due to the underrecognition
      of the disease, its increasing description in adults, and the fact that it may be
      a great imitator of gastroesophageal reflux disease. Symptoms may be protean
      including heartburn, dysphagia, nausea, vomiting, and abdominal pain accompanied
      by a history of atopic illnesses. Similarly, endoscopic and radiographic
      appearances may vary, ranging from stricture and "ring" formation to a completely
      normal-appearing esophagus, with diagnosis made only on biopsy sampling
      throughout the entire esophagus. Because this disease is thought to be allergic
      in origin, primary therapy is an attempt to identify and exclude possible food
      allergens through skin testing. Owing to the inability to identify an allergen
      or, conversely, poor compliance with a diet avoiding multiple food allergens,
      steroids may be useful in this disease. Strictures often require dilation as well
      owing to the chronic and fibrotic nature of these lesions.

PMID- 12521574
TI  - Esophageal Intramural Pseudodiverticulosis.
AB  - Esophageal intramural pseudodiverticulosis (EIPD) is an uncommon esophageal
      abnormality that is best diagnosed with a barium esophagram. The disorder is
      usually associated with other esophageal pathology, including strictures,
      motility disturbances, and other conditions that are outlined later. There is no
      specific treatment (either surgical or medical) for EIPD itself, and treatment
      should be directed at the underlying, associated conditions. If this condition is
      diagnosed on a barium study, endoscopy usually is needed to treat an associated
      stricture or to diagnose an associated inflammatory condition (particularly acid
      reflux and esophageal infections). Thus, endoscopy and barium studies are
      critical to guide the management of this condition.

PMID- 12521573
TI  - Infectious Esophagitis.
AB  - Infectious esophagitis can have significant implications in an impaired host.
      Described most commonly in immunocompromised patients, infectious esophagitis can
      also occasionally be discovered in immunocompetent individuals in several unique
      clinical settings. Evaluation of the typical presenting complaints, such as
      dysphagia or odynophagia, are especially important in immunocompetent patients,
      and therapy should be directed at the appropriate predisposing condition and
      resultant infectious agent. In immunocompromised patients, however, clinical
      experience supports the use of empiric therapy in patients without concomitant
      systemic complaints. Especially in AIDS patients or those with lymphoma or
      leukemia, the initial approach to infectious esophagitis complaints (ie,
      dysphagia or odynophagia) is to begin an empiric trial of oral systemic
      fluconazole for presumed candidal esophagitis. If the individual remains
      symptomatic after 3 to 7 days or has any associated systemic complaints or
      concerning clinical findings (eg, hematemesis), then upper endoscopy with
      biopsies is indicated. If an etiologic agent other than Candida is defined by
      histologic, immunohistochemical, or culture methods, then appropriate therapy can
      be initiated. There are many important and pathologic agents implicated in
      infectious esophagitis. Thus, directed therapy needs to be administered
      appropriately and in a timely fashion to avoid poor short-term problems or long
      term sequelae.

PMID- 12521575
TI  - Therapeutic Alternatives for the Mallory-Weiss Tear.
AB  - The Mallory-Weiss tear (MWT) is a frequent cause of upper gastrointestinal
      bleeding. It has been diagnosed more frequently since endoscopy was introduced.
      Once the diagnosis has been made, several treatment options are available. The
      treatment modality chosen depends on the type and location of the lesion, the
      patient's comorbid conditions, the availability of the different therapeutic
      modalities, and the experience of the endoscopist with each of these different
      modalities. In general, if the MWT is not actively bleeding at the time of
      endoscopy, no further treatment is needed owing to a low risk of rebleeding,
      unless a visible vessel is present. In the presence of a visible vessel or an
      actively bleeding vessel, then we recommend the use of any of the endoscopic
      treatment modalities discussed later in this article depending on the patient's
      condition and clinical scenario. Our review of the literature suggests that
      multipolar electric coagulation (MPEC) is the treatment modality with better
      evidence-based support for safety and bleeding control. MPEC has been associated
      only with very few complications. It should be avoided when esophageal varices
      are suspected because it may precipitate and aggravate bleeding. In such
      instances, either polidocanol injection or endoscopic band ligation of the tear
      is recommended, which is emerging as a safe and effective treatment modality even
      in patients without varices. In addition, epinephrine injection is an effective
      first-line modality. However, it should be avoided in patients with history of
      coronary artery disease owing to the potential for systemic absorption.
      Endoscopic hemoclipping (EH) is another useful treatment option and is emerging
      as a first-line modality. However, it is not widely available in all endoscopy
      emergency units. If it is available, it is a great alternative. Finally, if
      bleeding continues or recurs despite endoscopic therapy, the patient should be
      referred for surgical treatment. However, if the patient is not a surgical
      candidate, then radiologic hemostasis with selective vasopressin or Gelfoam
      embolization represents a viable treatment alternative that may be used depending
      on availability of a specialized interventional radiologist.

PMID- 12521576
TI  - Overview summary statement. Diagnosis and management of chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS).
AB  - Members of the Chronic Prostatitis Collaborative Research Network (CPCRN) met in
      a 1-day symposium to review recent findings and to debate unanswered issues in
      the diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS). The meeting was focused on producing an overview summary statement
      that would, as nearly as possible, represent the consensus views of the
      attendees. As discussed below, the participants agreed that a history, physical
      examination, and urinalysis/urine culture are mandatory for the evaluation of all
      patients presenting with CP/CPPS, with other assessments categorized as
      recommended or optional, depending on the history and physical findings.
      Observations and suggestions regarding first- and second-line therapies are also
      offered, with the recognition that randomized, placebo-controlled trials to guide
      selection of therapies for chronic nonbacterial prostatitis are currently
      lacking.

PMID- 12521577
TI  - Classification (traditional and National Institutes of Health) and demographics
      of prostatitis.
AB  - This article reviews the National Institutes of Health (NIH) classification
      system for prostatitis and summarizes the baseline analysis of the Chronic
      Prostatitis Cohort Study, a longitudinal study, which has enrolled 488 patients
      diagnosed with category III prostatitis. The prevalence of category IIIA in this
      cohort was 54% to 90%, depending on the cut points used. In all, 8% (37 of 488)
      had > or =1 localizing uropathogen. However, leukocyte and bacterial counts did
      not correlate with severity of symptoms as assessed by the NIH Chronic
      Prostatitis Symptom Index. Continued follow-up study of this cohort will likely
      answer important questions about the natural and treated history of this
      syndrome.

PMID- 12521579
TI  - Chronic prostatitis: epidemiology and role of infection.
AB  - We review the epidemiology of chronic prostatitis/chronic pelvic pain syndrome
      (CP/CPPS) and the role of infectious agents, emphasizing critical data necessary
      to define current research issues. The epidemiologic literature is limited, but
      the worldwide prevalence appears to be in the range of 2% to 10%, indicating that
      CP/CPPS represents an important international health problem. Recent molecular
      studies have documented bacterial DNA sequences in prostate tissue from CP/CPPS
      patients. These data suggest that colonization and/or infection occurs in the
      prostates of many patients with CP/CPPS. Further molecular research is needed to
      define the role of bacteria in the etiology of CP/CPPS.

PMID- 12521581
TI  - A review of the development and validation of the National Institutes of Health
      Chronic Prostatitis Symptom Index.
AB  - Chronic nonbacterial prostatitis or chronic pelvic pain syndrome (CPPS) causes
      morbidity, both through symptoms and associated impairment in health-related
      quality of life, both of which illustrate the importance of patient-centered
      outcomes. Despite preliminary work by several investigators, research and
      clinical efforts to provide help for men afflicted with CPPS have been hampered
      by the absence of a widely accepted, reliable, and valid instrument to measure
      symptoms and quality-of-life impact. Investigators from the National Institutes
      of Health (NIH)-funded Chronic Prostatitis Collaborative Research Network (CPCRN)
      sought to remedy this problem by developing a psychometrically valid index of
      symptoms and quality-of-life impact in men with chronic prostatitis. This
      instrument, now validated in English, Spanish, German, and Korean, is known as
      the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). It contains 13 items that
      are scored in 3 discrete domains: pain, urinary symptoms, and quality-of-life
      impact. In early studies, the NIH-CPSI has been shown to be reliable, valid, and
      responsive to change. Further work is needed to determine whether it performs as
      well in minority populations, men seeking care in nonreferral centers, and other
      diverse populations.

PMID- 12521583
TI  - Clinical evaluation of the man with chronic prostatitis/chronic pelvic pain
      syndrome.
AB  - The various investigative procedures used in clinical, laboratory, and imaging
      evaluations for the patient presenting with chronic pelvic pain are discussed and
      categorized as mandatory, recommended, or optional procedures. These categories
      primarily serve to rule out underlying pathology because there is no diagnostic
      test for chronic prostatitis/chronic pelvic pain syndrome (CPPS). Mandatory
      category investigations should be performed in all patients with CPPS, and those
      procedures categorized as recommended or optional are generally prompted by
      specific findings in the history or physical examination, or by poor response to
      standard therapies.

PMID- 12521585
TI  - Antimicrobial therapy for bacterial and nonbacterial prostatitis.
AB  - Antimicrobial therapy is the standard of care for the unusual man with true
      chronic bacterial prostatitis but does not have much of a role in the treatment
      of men with nonbacterial prostatitis. The fluoroquinolone antibiotics given for 2
      to 4 weeks will cure about 70% of chronic bacterial infections of the prostate.
      If this treatment fails, the symptomatic manifestations of the infections can
      almost always be eliminated with suppressive antimicrobial therapy using
      trimethoprim-sulfamethoxazole, a fluoroquinolone antibiotic, or nitrofurantoin.

PMID- 12521587
TI  - Role of alpha-blockers in the treatment of chronic prostatitis.
AB  - Treatment of nonbacterial chronic prostatitis/chronic pelvic pain syndrome
      continues to be a challenge for the treating physician. However, results from
      studies on the use of alpha-blockers seem to show some promise. Further studies
      on this class of drugs in the treatment of this condition are recommended.

PMID- 12521589
TI  - Inflammation and anti-inflammatory therapy in chronic prostatitis.
AB  - Anti-inflammatory medications have been used for the treatment of chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS), given that inflammation and
      pain are traditionally associated with this condition. The National Institutes of
      Health (NIH) classification divides category III into (1) category IIIA--patients
      with white blood cells (WBCs) in their expressed prostatic secretions, post
      prostate massage urine (voided bladder urine-3 [VB3]) or semen; and (2) category
      IIIB--those without WBCs. However, recent studies indicate that the ability of
      WBC count alone to distinguish men with symptoms from those without appears
      limited. Other markers of inflammation, such as cytokines, may correlate better
      with clinical findings. The mechanisms of inflammation continue to be
      investigated, including contributions from reactive oxygen species, autoimmune
      response, neurogenic inflammation, and even endocrine dysfunction. There have
      been few controlled studies of anti-inflammatory therapy for chronic prostatitis.
      In the only randomized double-blind placebo-controlled trial, the NIH-Chronic
      Prostatitis Symptom Index (CPSI) total, domain, and pain scores significantly
      decreased from baseline in all groups, but the difference was not statistically
      significant. Other medications that have some theoretic anti-inflammatory
      properties have shown promising early results. Further study of currently
      available anti-inflammatory medications may be warranted, especially in longer
      trials, which may allow resolution of the significant placebo effect commonly
      seen in the short term in men with CPPS. Further discussion is needed to either
      validate, modify, or abolish the distinction between category IIIA and IIIB in
      the NIH classification.

PMID- 12521591
TI  - Phytotherapy in chronic prostatitis.
AB  - Chronic prostatitis is a very common condition that is poorly understood and has
      a significant impact on quality of life. Given the lack of proven efficacy of
      conventional therapies, such as antibiotics, it is not surprising that patients
      have turned with increasing frequency to phytotherapy and other alternative
      treatments. Although alternative therapies are plentiful, few have been subjected
      to scientific scrutiny and prospective controlled clinical trials. This review
      will cover phytotherapies commonly used in prostatitis patients and focus in
      detail on those with published data. These treatments include zinc, cernilton
      (bee pollen), quercetin, and saw palmetto. Although many of these therapies
      appear promising in small preliminary studies, phytotherapy requires the same
      scientific criteria for validation and acceptance as do conventional medical
      therapies.

PMID- 12521593
TI  - Heat therapy in the treatment of prostatitis.
AB  - There is a dearth of literature on heat therapy and prostatitis. The therapies
      used different energy sources, including interstitial heat and microwaves, and
      were delivered both transrectally and transurethrally. Most data precede our
      present system of nomenclature and therefore are difficult to compare, even with
      the literature of their day. Validated instruments were rarely used to determine
      efficacy, and most outcome measures were subjective. We will need well-designed
      prospective clinical trials using objective outcome measures and validated
      symptom indexes. Until then the use of heat therapy for prostatitis should be
      considered experimental.

PMID- 12521595
TI  - Bladder training biofeedback and pelvic floor myalgia.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating
      condition, traditionally treated with antimicrobials, nonsteroidal anti
      inflammatory drugs, and alpha-blockers. Pelvic floor tension myalgia is
      hypothesized to be a contributing factor in CPPS. Biofeedback training for CPPS
      is based on the principle that maximum muscle contraction prompts maximum muscle
      relaxation. Similar chronic pain conditions have been treated successfully with
      biofeedback-assisted techniques of neuromuscular reeducation. Preliminary study
      by our group has shown biofeedback, pelvic floor reeducation, and bladder
      training to be helpful in the treatment of CP/CPPS. Overall, 8 of 11 patients had
      improvement in either pain scores or their chronic prostatitis pain index scores.
      With no cure for CP/CPPS available, biofeedback and pelvic floor reeducation
      merit further evaluation in the treatment of this condition.

PMID- 12521597
TI  - Biological significance of phospholipid hydroperoxide glutathione peroxidase
      (PHGPx, GPx4) in mammalian cells.
AB  - Reactive oxygen species (ROS) are known mediators of intracellular signal
      cascades. Excessive production of ROS may lead to oxidative stress, loss of cell
      function, and cell death by apoptosis or necrosis. Lipid hydroperoxides are one
      type of ROS whose biological function has not yet been clarified. Phospholipid
      hydroperoxide glutathione peroxidase (PHGPx, GPx4) is a unique antioxidant enzyme
      that can directly reduce phospholipid hydroperoxide in mammalian cells. This
      contrasts with most antioxidant enzymes, which cannot reduce intracellular
      phospholipid hydroperoxides directly. In this review, we focus on the structure
      and biological functions of PHGPx in mammalian cells. Recently, molecular
      techniques have allowed overexpression of PHGPx in mammalian cell lines, from
      which it has become clear that lipid hydroperoxides also have an important
      function as activators of lipoxygenase and cyclooxygenase, participate in
      inflammation, and act as signal molecules for apoptotic cell death and receptor
      mediated signal transduction at the cellular level.

PMID- 12521598
TI  - Topical alpha-tocotrienol supplementation inhibits lipid peroxidation but fails
      to mitigate increased transepidermal water loss after benzoyl peroxide treatment
      of human skin.
AB  - Benzoyl peroxide (BPO) is a commonly used drug in the treatment of acne vulgaris,
      but it induces unwanted side effects related to stratum corneum (SC) function.
      Since it has been recently shown to oxidize SC antioxidants, it was hypothesized
      that antioxidant supplementation may mitigate the BPO-induced SC changes. To test
      this, 11 subjects were selected to be topically supplemented with alpha
      tocotrienol (5% w/vol) for 7 d on defined regions of the upper back, while the
      contralateral region was used for vehicle-only controls. Starting on day 8, all
      test sites were also treated with BPO (10%) for 7 d; the alpha-tocotrienol
      supplementation was continued throughout the study. A single dose of BPO depleted
      93.2% of the total vitamin E. While continuing the BPO exposure for 7 d further
      depleted vitamin E in both vehicle-only and alpha-tocotrienol-treated sites,
      significantly more vitamin E remained in the alpha-tocotrienol-treated areas.
      Seven BPO applications increased lipid peroxidation. Alpha-tocotrienol
      supplementation significantly mitigated the BPO-induced lipid peroxidation. The
      transepidermal water loss was increased 1.9-fold by seven BPO applications, while
      there was no difference between alpha-tocotrienol treatment and controls. The
      data suggest that alpha-tocotrienol supplementation counteracts the lipid
      peroxidation but not the barrier perturbation in the SC induced by 10% BPO.

PMID- 12521599
TI  - Site-activity relationship of nitroxide radical's antioxidative effect.
AB  - A relatively new strategy in preventing oxidative damage employs cyclic
      nitroxides. These stable radicals have been widely used as biophysical probes,
      spin labels, and are currently tested as contrast agents for nuclear magnetic
      resonance imaging. Nitroxides were found to protect cells, organs, and whole
      animals against diverse oxidative insults. The present study concentrated on
      comparing the antioxidative activity of nitroxides against oxidative damage,
      initiated either in the lipid or aqueous phase, to egg phosphatidylcholine acyl
      chains (13.4% polyunsaturated fatty acids) in small unilamellar vesicles. We
      determined the lipophilicity and liposome-membrane/aqueous-medium partition
      coefficient for several nitroxides and compared their specific protective
      effects. The aim was to study the relation between nitroxides' concentration,
      location in the lipid bilayer, and their protection against oxidative damage.
      Both 6-membered- and 5-membered-ring nitroxides were studied for: (i)
      partitioning between the lipid bilayer and the aqueous phase (nitroxides were
      quantified using EPR spectroscopy); (ii) the intrabilayer distribution, using
      three different fluorescent probes of known location of their fluorophors in the
      lipid bilayer; and (iii) the specific antioxidative effect (protection per
      concentration) against radicals formed in a liposomal dispersion. The radicals
      were generated using the thermolabile, radical-generating compounds 2,2'-azobis
      (2-amidinopropane) dihydrochloride (AAPH) in the aqueous phase, and 2,2'-azobis
      (2,4-dimethyl-valeronitrile) (AMVN) in the lipid phase. The results show that
      nitroxides react, in a concentration-dependent manner, with deleterious species
      at their formation sites, both in the aqueous and the lipid phase, and that their
      specific protective effects for the lipophilic target, the lipid bilayer, are
      similar for both the lipophilic and the hydrophilic nitroxides.

PMID- 12521600
TI  - Early oxidative stress in the diabetic kidney: effect of DL-alpha-lipoic acid.
AB  - Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The
      attempts to identify early markers of diabetes-induced renal oxidative injury
      resulted in contradictory findings. We characterized early oxidative stress in
      renal cortex of diabetic rats, and evaluated whether it can be prevented by the
      potent antioxidant, DL-alpha-lipoic acid. The experiments were performed on
      control rats and streptozotocin-diabetic rats treated with/without DL-alpha
      lipoic acid (100 mg/kg i.p., for 3 weeks from induction of diabetes).
      Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic
      rats vs. controls (p <.01) and this increase was partially prevented by DL-alpha
      lipoic acid. F(2) isoprostane concentrations (measured by GCMS) expressed per
      either mg protein or arachidonic acid content were not different in control and
      diabetic rats but were decreased several-fold with DL-alpha-lipoic acid
      treatment. Both GSH and ascorbate (AA) levels were decreased and GSSG/GSH and
      dehydroascorbate/AA ratios increased in diabetic rats vs. controls (p <.01 for
      all comparisons), and these changes were completely or partially (AA) prevented
      by DL-alpha-lipoic acid. Superoxide dismutase, glutathione peroxidase,
      glutathione reductase, glutathione transferase, and NADH oxidase, but not
      catalase, were upregulated in diabetic rats vs. controls, and these activities,
      except glutathione peroxidase, were decreased by DL-alpha-lipoic acid. In
      conclusion, enhanced oxidative stress is present in rat renal cortex in early
      diabetes, and is prevented by DL-alpha-lipoic acid.

PMID- 12521601
TI  - Nonradical mechanism of (bi)sulfite reaction with DEPMPO: cautionary note for
      SO3*- radical spin trapping.
AB  - Knowledge of the formation of radicals from sulfites, in vivo, is of interest in
      understanding the allergic and inflammatory responses to environmental sulfur
      dioxide exposure. Sulfite anion trioxide (SO(3)(-*)) radical formation was
      measured in mice, preloaded with the spin trap, 5-(diethoxy-phosphoryl)-5-methyl
      pyrrolidine-N-oxide, (DEPMPO). Based on spin trapping NMR, a surprising quantity
      of reduced SO(3)(-*)-adduct was observed that did not depend on co-administration
      of oxidizing agents, suggesting a possible nonradical reaction between
      (bi)sulfite and DEPMPO. The products of the reversible nucleophylic addition of
      (bi)sulfite to the nitrone functional group were identified using (31)P-NMR, (1)H
      NMR, and (13)C-NMR spectroscopy as cis- and trans- stereoisomers of hydroxylamine
      and confirmed by quantum chemical calculations. Oxidation of the hydroxylamines
      results in the formation of two corresponding cis- and trans-isomeric nitroxides,
      only one of which has been earlier described as the paramagnetic adduct of
      genuinely trapped SO(3)(-*) radical. The results demonstrate that SO(3)(-*)
      detection using nitrone spin traps such as DEPMPO and DMPO may involve nonradical
      addition reactions except in cases when the required controls unambiguously prove
      a radical mechanism.

PMID- 12521602
TI  - Ectopic expression of catalase in Drosophila mitochondria increases stress
      resistance but not longevity.
AB  - The goal of this study was to test the hypothesis that the rate of mitochondrial
      oxidant production governs the aging process of the fruit fly, Drosophila
      melanogaster. Catalase, an antioxidative enzyme expressed in the cytosol and
      peroxisomes of Drosophila, was targetted ectopically to the mitochondrial matrix
      by fusion of a leader peptide derived from ornithine aminotransferase with its N
      terminus. The presence of the transgene encoding this fusion protein was
      associated with moderate (35 +/- 13%) increases in total catalase activity in
      most lines, and measurable levels of catalase activity in the mitochondria (30
      140 U/mg protein). There was no impact on the life span of the flies at 25
      degrees C, even in an exceptional line with a 149% increase in total catalase
      activity, and there was a small decrease in longevity at 29 degrees C. There were
      no compensatory changes in the rate of metabolism or physical activity, or in the
      levels of other major antioxidants, suggesting that the aging process was largely
      unaffected. Resistance to exogenous hydrogen peroxide, paraquat, and cold stress
      was enhanced, but there was no appreciable effect on resistance to hyperoxia. The
      results demonstrate the importance of mitochondrial antioxidant levels in the
      resistance to oxidative stress at the organismal level, and illustrate that
      different effects on aging and stress resistance may ensue from a single
      treatment. The main inferences drawn are that: (i) levels of stress resistance
      may neither be a cause nor a reliable indicator of the rate of aging, and (ii)
      bolstering antioxidant levels in Drosophila may not delay or slow down the aging
      process.

PMID- 12521604
TI  - Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele
      of Gpdx(a) encoding glucose 6-phosphate dehydrogenase.
AB  - Mice harboring the activity-attenuated Gpdx(a-m2Neu) allele and also harboring a
      chromosomally integrated lacZ reporter gene to study mutagenesis (pUR288) were
      used to demonstrate that moderate glucose 6-phosphate dehydrogenase (G6PD)
      deficiency causes elevated mutagenesis and endogenous oxidative stress in the
      spleen. G6PD-deficient spleens with a residual enzyme activity of 22% exhibited a
      dramatic shift in the mutational pattern of lacZ (4.6-fold increase in the
      prevalence of recombination mutations of lacZ) together with a 1.8-fold increase
      in mutant frequencies in lacZ. A concomitant 3-fold reduction in catalase
      activity (dependent upon NADPH) indicated that the in vivo supply of G6PD
      generated NADPH was insufficient. An additional 3-fold increase in oxidized
      glutathione suggested that redox control was disturbed in G6PD-deficient spleens.
      These findings indicate that G6PD is required for limiting oxidative mutagenesis
      in the mouse spleen. Gpdx(a-m2Neu) is the first hypomorphic allele of a mouse
      housekeeping gene associated with elevated somatic mutagenesis in vivo.

PMID- 12521603
TI  - Deoxycytidine glyoxal: lesion induction and evidence of repair following vitamin
      C supplementation in vivo.
AB  - Oxidative DNA damage is postulated to be involved in carcinogenesis, and as a
      consequence, dietary antioxidants have received much interest. A recent report
      indicates that vitamin C facilitates the decomposition of hydroperoxides in
      vitro, generating reactive aldehydes. We present evidence for the in vivo
      generation of glyoxal, an established product of lipid peroxidation,
      glucose/ascorbate autoxidation, or free radical attack of deoxyribose, following
      supplementation of volunteers with 400 mg/d vitamin C. Utilizing a monoclonal
      antibody to a deoxycytidine-glyoxal adduct (gdC), we measured DNA lesion levels
      in peripheral blood mononuclear cells. Supplementation resulted in significant (p
      =.001) increases in gdC levels at weeks 11, 16, and 21, with corresponding
      increases in plasma malondialdehyde levels and, coupled with previous findings,
      is strongly suggestive of a pro-oxidative effect. However, continued
      supplementation revealed a highly significant (p =.0001) reduction in gdC levels.
      Simultaneous analysis of cyclobutane thymine dimers revealed no increase upon
      supplementation but, as with gdC, levels decreased. Although no single mechanism
      is identified, our data demonstrate a pro-oxidant event in the generation of
      reactive aldehydes following vitamin C supplementation in vivo. These results are
      also consistent with our hypothesis for a role of vitamin C in an adaptive/repair
      response and indicate that nucleotide excision repair specifically may be
      affected.

PMID- 12521605
TI  - In vitro studies on the photobiological properties of aloe emodin and aloin A.
AB  - Plants containing aloin A, aloe emodin, and structurally related anthraquinones
      have long been used as traditional medicines and in the formulation of retail
      products such as laxatives, dietary supplements, and cosmetics. Since a recent
      study indicated that topically applied aloe emodin increases the sensitivity of
      skin to UV light, we examined the events following photoexcitation of aloin A and
      aloe emodin. We determined that incubation of human skin fibroblasts with 20
      microM aloe emodin for 18 h followed by irradiation with UV or visible light
      resulted in significant photocytotoxicity. This photocytotoxicity was accompanied
      by oxidative damage in both cellular DNA and RNA. In contrast, no
      photocytotoxicity was observed following incubation with up to 500 microM aloin A
      and irradiation with UVA light. In an attempt to explain the different
      photobiological properties of aloin A and aloe emodin, laser flash photolysis
      experiments were performed. We determined that the triplet state of aloe emodin
      was readily formed following photoexcitation. However, no transient intermediates
      were formed following photoexcitation of aloin A. Therefore, generation of
      reactive oxygen species and oxidative damage after irradiation of aloin A is
      unlikely. Although aloin A was not directly photocytotoxic, we found that human
      skin fibroblasts can metabolize aloin A to aloe emodin.

PMID- 12521606
TI  - Dietary flavonoid iron complexes as cytoprotective superoxide radical scavengers.
AB  - Superoxide radicals have been implicated in the pathogenesis of
      ischemia/reperfusion, aging, and inflammatory diseases. In the present work, we
      have shown that the Fe(3+) complexes of flavonoids (polyphenols) were much more
      effective than the uncomplexed flavonoids in protecting isolated rat hepatocytes
      against hypoxia-reoxygenation injury. The 2:1 flavonoid-metal complexes of
      Cu(2+), Fe(2+), or Fe(3+) were more effective than the parent compounds in
      scavenging superoxide radicals generated by xanthine oxidase/hypoxanthine (an
      enzymatic superoxide-generating system). The 2:1 [flavonoid:Fe(3+)] complexes but
      not the [deferoxamine:Fe(3+)] complex readily scavenged superoxide radicals.
      These results suggest that the initial step in superoxide radical scavenging
      (SRS) activity involves a redox-active flavonoid:Fe(3+) complex. Flavonoid:Fe(3+)
      complexes should, therefore, be tested as a therapy for the treatment of
      ischemia/reperfusion injury.

PMID- 12521607
TI  - Hemoprotein-mediated reduction of nitrated DNA bases in the presence of reducing
      agents.
AB  - DNA damages by reactive nitrogen oxide species may contribute to the multistage
      carcinogenesis processes associated with chronic infections and inflammation. The
      nitrated DNA adducts 8-nitroguanine (8NG) and 8-nitroxanthine (8NX) have been
      shown to derive from these reactive nitrogen oxide species, but they are not
      stable in DNA since they undergo spontaneous depurination. We herein report that
      hemin and hemoproteins, including hemoglobin and cytochrome c, mediate reduction
      of 8NG and 8NX to their corresponding amino analogues in the presence of reducing
      agents under physiologically relevant conditions. This reaction is believed to
      involve the reduced heme moiety produced from the reduction of oxidized
      hemoglobin or cytochrome c by reducing agents. The combination of hemoglobin and
      dihydrolipoic acid generated the reduced products in high yields. Ascorbate,
      quercetin, and glutathione are also capable of reducing these nitrated DNA
      adducts. The hemoglobin macromolecule reduces 8NG and 8NX formed in nitryl
      chloride-treated calf thymus DNA, as evidenced by the formation of the amino
      adducts using reversed-phase HPLC with photodiode array detection. Hemin is more
      efficient than equal molar of heme on hemoglobin in reducing 8NG-containing DNA,
      indicating the role of protein in impeding the reaction. Furthermore, we also
      show that the reduction product 8-aminoguanine is persistent on DNA. These
      findings suggest that reduction of nitrated DNA by the heme/antioxidant system
      might represent a possible in vivo pathway to modify DNA nitration.

PMID- 12521608
TI  - Inhibition of heat shock protein 90 (hsp90) in proliferating endothelial cells
      uncouples endothelial nitric oxide synthase activity.
AB  - Dual increases in nitric oxide ((*)NO) and superoxide anion (O(2)(*-)) production
      are one of the hallmarks of endothelial cell proliferation. Increased expression
      of endothelial nitric oxide synthase (eNOS) has been shown to play an important
      role in maintaining high levels of (*)NO generation to offset the increase in
      O(2)(*-) that occurs during proliferation. Although recent reports indicate that
      heat shock protein 90 (hsp90) associates with eNOS to increase (*)NO generation,
      the role of hsp90 association with eNOS during endothelial cell proliferation
      remains unknown. In this report, we examine the effects of endothelial cell
      proliferation on eNOS expression, hsp90 association with eNOS, and the mechanisms
      governing eNOS generation of (*)NO and O(2)(*-). Western analysis revealed that
      endothelial cells not only increased eNOS expression during proliferation but
      also hsp90 interactions with the enzyme. Pretreatment of cultures with radicicol
      (RAD, 20 microM), a specific inhibitor that does not redox cycle, decreased
      A23187-stimulated (*)NO production and increased L(omega)
      nitroargininemethylester (L-NAME)-inhibitable O(2)(*-) generation. In contrast,
      A23187 stimulation of controls in the presence of L-NAME increased O(2)(*-)
      generation, confirming that during proliferation eNOS generates (*)NO. Our
      findings demonstrate that hsp90 plays an important role in maintaining (*)NO
      generation during proliferation. Inhibition of hsp90 in vascular endothelium
      provides a convenient mechanism for uncoupling eNOS activity to inhibit (*)NO
      production. This study provides new understanding of the mechanisms by which
      ansamycin antibiotics inhibit endothelial cell proliferation. Such information
      may be useful in the development and design of new antineoplastic agents in the
      future.

PMID- 12521609
TI  - No increase in lifespan in Caenorhabditis elegans upon treatment with the
      superoxide dismutase mimetic EUK-8.
AB  - The superoxide dismutase mimetic EUK-8 has been reported to extend lifespan in
      the nematode Caenorhabditis elegans. However, in five trials administering EUK-8
      in liquid culture with E. coli, and two trials using defined liquid medium, we
      observed no increase in C. elegans lifespan. Instead we saw a dose-dependent
      reduction of lifespan and fertility. We conclude that extension of C. elegans
      lifespan by EUK-8 may only occur under very particular culture conditions.

PMID- 12521610
TI  - Drotrecogin Alfa (Activated): From Bench to Practical Use at the Bedside.
      Proceedings of meetings of the Protein C Worldwide Evaluation in Severe Sepsis
      (PROWESS) Clinical Evaluation Committee.

PMID- 12521611
TI  - Severe sepsis.

PMID- 12521612
TI  - Introduction: rationale for using drotrecogin alfa (activated) in patients with
      severe sepsis.

PMID- 12521613
TI  - Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.
AB  - Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and
      Company, Indianapolis, IN) therapy outside of a clinical trial setting requires
      knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe
      Sepsis (PROWESS) investigators to select the various entry criteria for the
      trial. Enrollment criteria for the study included a known or suspected infection,
      presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria,
      and dysfunction of > or =1 organ or system. The infection criteria used in
      PROWESS were designed to be straightforward and were based on common clinical and
      radiological data. Although previous definitions of sepsis required only 2 SIRS
      criteria, the PROWESS trial investigators required the presence of > or =3 SIRS
      criteria to improve the sensitivity and specificity of these criteria for the
      diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe
      sepsis, was used to define the study population because it identifies patients at
      significant risk of death. Characteristics of drotrecogin alfa (activated)
      treated patients, including infection, modified SIRS criteria, and organ
      dysfunction, were similar to those of the placebo group and the general sepsis
      population. Proper clinical judgment and use of the these inclusion criteria as a
      guide will help clinicians select and treat sepsis patients with drotrecogin alfa
      (activated).

PMID- 12521614
TI  - Identifying patients with severe sepsis who should not be treated with
      drotrecogin alfa (activated).
AB  - Historically, clinical trials evaluating treatment of patients with severe sepsis
      have failed to show a reduction of mortality. However, retrospective analyses of
      some of these trials showed benefits in certain patient subgroups. Conversely,
      the recent Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, which
      evaluated the safety and efficacy of drotrecogin alfa (activated) (Xigris; Eli
      Lilly and Company, Indianapolis, IN), a recombinant form of human activated
      protein C, in adult patients with severe sepsis, is notable in that it is the
      first trial to show a reduction in 28-day all-cause mortality in the intent-to
      treat population compared with the placebo group. When assessing a new
      intervention, patient exclusion criteria are important considerations in
      evaluating the evidence from a controlled clinical trial. Appropriate patient
      selection will be a key factor in the use of this newly approved therapeutic
      agent to treat severe sepsis. A review of the exclusion criteria used in the
      PROWESS trial should provide clinicians with a way of differentiating those
      patients in the critical care setting who will benefit most from treatment with
      drotrecogin alfa (activated) from those who should not be treated.

PMID- 12521615
TI  - Risk-benefit analysis for drotrecogin alfa (activated).
AB  - An analysis of risks and benefits is an important component of patient care.
      Drotrecogin alfa (activated), the first approved cogin (a class of recombinant
      human coagulation inhibitors), provides a clear example of a treatment that
      requires a careful risk-benefit analysis. Treatment with this novel compound has
      been shown to reduce significantly the risk of death in patients with sepsis and
      acute organ dysfunction (severe sepsis). However, the drug is a natural
      antithrombotic that can increase the risk of bleeding in recipients. We will
      discuss bleeding and other potential risks associated with drotrecogin alfa
      (activated) treatment, as well as the survival benefits seen with the use of this
      therapy in patients with severe sepsis.

PMID- 12521616
TI  - Management of patients with severe sepsis, treated by drotrecogin alfa
      (activated).
AB  - A number of management issues confront the clinician treating a critically ill
      patient with drotrecogin alfa (activated) (Xigris; Eli Lilly and Company,
      Indianapolis, IN), a compound documented to significantly reduce the risk of 28
      day all-cause mortality in patients with severe sepsis. The management issues
      that will be discussed include differentiating drug effect from the hemostatic
      changes of sepsis, prevention and management of bleeding during drotrecogin alfa
      (activated) infusion, treatment considerations in the patient with
      thrombocytopenia or disseminated intravascular coagulation, thromboprophylaxis in
      drug-treated patients, and the use of drotrecogin alfa (activated) in patients
      requiring renal replacement therapy. Proper adherence to principles described in
      this article can facilitate patient management and reduce the risk of bleeding.

PMID- 12521617
TI  - Conclusions: drotrecogin alfa (activated)--from bench to practical use at the
      bedside.

PMID- 12521620
TI  - Predictors of cardiac and noncardiac mortality among 14,697 patients with
      coronary heart disease.
AB  - The decrease in mortality from ischemic heart disease during the last 25 years
      may partly reflect improvement in diagnosis and treatment of patients with
      coronary heart disease. These patients, therefore, are experiencing morbidity and
      mortality due to other causes. The aim of our study was to describe the incidence
      and causes of cardiac mortality (CM) and noncardiac mortality (NCM) and to
      identify predictive factors. A cohort of 14,697 patients with coronary heart
      disease was merged with the Central Population Registry to identify mortality
      records from 1990 to 1996. Among the 1,839 deaths, 1,055 (57.4%) were cardiac,
      626 (34.0%) were noncardiac, and 158 deaths (8.6%) were due to unknown causes as
      classified in the International Classification of Diseases-Ninth Edition (ICD).
      The 3 most significant predictors were age for a 10-year increment (odds ratios
      1.75 and 2.25 for CM and NCM, respectively), chronic obstructive pulmonary
      disease (odds ratios 1.67 and 1.71), and current smoking (odds ratios 1.29 and
      1.66). A history of cancer was a predictor of NCM, but not of CM, whereas
      peripheral vascular disease predicted CM but not NCM. As the number of predictive
      factors increased from none to >or=5, the risk of NCM gradually increased from
      1.9% to 15.5%. Similar predictors expose subjects with coronary disease to CM and
      NCM, but smoking plays a more pronounced role in the prediction of NCM, whereas
      past myocardial infarction, lower levels of high-density lipoprotein cholesterol,
      and peripheral vascular disease are mainly associated with CM. Because of the
      similarity of antecedent predictors, treatment of risk factors among patients
      with coronary heart disease should prove valuable for the prevention of all-cause
      mortality.

PMID- 12521621
TI  - Effect of prodromal angina pectoris on altering the relation between time to
      reperfusion and outcomes after a first anterior wall acute myocardial infarction.
AB  - To test the hypothesis that prodromal angina may favorably alter the relation
      between time to reperfusion and outcomes after acute myocardial infarction (AMI),
      we studied 658 patients with a first anterior AMI: 200 patients with early
      reperfusion (time to reperfusion <or=2 hours), 205 patients with intermediate
      reperfusion (2 to 4 hours), 197 patients with late reperfusion (4 to 12 hours),
      and 56 patients without reperfusion (no reperfusion). Serial measurements of left
      ventricular ejection fraction (LVEF) were obtained before reperfusion therapy and
      before hospital discharge in 450 patients. Thirty-day mortality (3%, 4%, 8%, and
      27% in early, intermediate, late, and no reperfusion, respectively, p <0.001) and
      the change in LVEF (8 +/- 14%, 6 +/- 13%, 6 +/- 12%, and -1 +/- 9%, respectively,
      p <0.001) were dependent on time to reperfusion and were worse if reperfusion was
      not obtained. In early reperfusion, 30-day mortality (3% vs 2%, p = 0.88) and
      improvement of LVEF (9 +/- 14% vs 8 +/- 14%, p = 0.59) were not significantly
      different between patients with prodromal angina and patients without prodromal
      angina. In intermediate or late reperfusion, prodromal angina was associated with
      lower 30-day mortality (3% vs 8%, p = 0.049) and a greater improvement in LVEF (8
      +/- 13% vs 5 +/- 13%, p = 0.037). In no reperfusion, 30-day mortality (25% vs
      27%, p = 0.87) and the change in LVEF (-1 +/- 11% vs -1 +/- 9, p = 0.87) were
      poor, regardless of prodromal angina. These findings suggest that prodromal
      angina might favorably alter the relation between time to reperfusion and
      outcomes after AMI. However, prodromal angina did not afford any benefits if
      reperfusion was not achieved.

PMID- 12521622
TI  - Concentrations of interleukins, interferon, and C-reactive protein in stable and
      unstable angina pectoris.
AB  - We analyzed the concentrations of interleukins (IL)-6, IL-10, IL-12, and IL-18,
      interferon (IFN)-gamma, and high-sensitivity C-reactive protein (hsCRP) in 40
      patients with unstable angina (UAP), 39 patients with stable angina (SAP), and 52
      age- and gender-matched controls. Compared with the control group, IL-12
      concentrations were significantly higher in both the SAP and UAP groups,
      especially in the UAP group, and the IL-18 concentrations tended to be higher in
      the UAP group. Conversely, IL-10 concentrations were significantly lower in the
      SAP and UAP groups. Both IL-6 and hsCRP concentrations were significantly higher
      in the UAP group. The levels of hsCRP were positively correlated with
      inflammatory or proinflammatory cytokines (IL-6, IL-12, and IL-18), and
      negatively correlated with anti-inflammatory cytokine (IL-10). Moreover, the
      levels of IL-12 were positively correlated with IL-18, and negatively correlated
      with IL-10, and the results revealed the T-helper 1 dominant state. These results
      suggested that the inflammatory response was strongly associated with coronary
      atherosclerosis and angina pectoris, and that the T-helper 1 dominance may play
      an important role in these diseases.

PMID- 12521623
TI  - Effects of propranolol on recovery of heart rate variability following acute
      myocardial infarction and relation to outcome in the Beta-Blocker Heart Attack
      Trial.
AB  - This study evaluated the effects of propranolol on recovery of heart rate
      variability (HRV) after acute myocardial infarction and its relation to outcome
      in the Beta-blocker Heart Attack Trial (BHAT). Beta blockers improve mortality
      after acute myocardial infarction, but through an unknown mechanism. Depressed
      HRV, a measure of autonomic tone, predicts mortality after acute myocardial
      infarction. Whether beta blockers influence recovery of HRV after acute
      myocardial infarction, and thereby improve outcome, is unknown. We compared 24
      hour HRV parameters at 1 week after acute myocardial infarction and after 6 weeks
      of treatment with propanolol (n = 88) or placebo (n = 96). The relation between
      25-month outcome (death/acute myocardial infarction/congestive heart failure),
      propranolol treatment, and HRV was further analyzed. After 6 weeks, high
      frequency (HF) power (log-normalized), an index of vagal tone, increased more in
      propranolol-treated patients (4.28 +/- 0.1 to 5.17 +/- 0.09 ms(2)) than in
      placebo-treated patients (4.26 +/- 0.09 to 4.77 +/- 0.1 ms(2), p <0.05).
      Sympathovagal balance measured by the low-frequency (LF) to HF ratio increased in
      placebo-treated patients (3.55 +/- 0.24 to 3.86 +/- 0.24) but decreased in those
      treated with propranolol (3.76 +/- 0.29 to 3.17 +/- 0.23, p <0.01). Other
      frequency-domain parameters increased over time but were not affected by
      propranolol. Propranolol blunted the morning increase in the LF/HF ratio.
      Recovery of HF, the strongest HRV predictor of outcome, and propranolol therapy
      independently predicted outcome. In summary, after acute myocardial infarction,
      propranolol therapy improves recovery of parasympathetic tone, which correlates
      with improved outcome, and decreases morning sympathetic predominance. These
      findings may elucidate the mechanisms by which beta blockers decrease mortality
      and reduce the early morning risk of sudden death after acute myocardial
      infarction.

PMID- 12521624
TI  - Cost-effectiveness of intracoronary ultrasound for percutaneous coronary
      interventions.
AB  - The Strategy for Intravascular Ultrasound (IVUS) guided PTCA and Stenting trial
      included a prospectively designed economic analysis to investigate whether
      routine IVUS guidance intervention is cost-effective. Consecutive patients (n =
      269) with 356 lesions were randomly assigned to receive provisional stenting with
      angiographic guidance only (ANGIO) or with IVUS guidance. The 2-year major
      adverse cardiac event-free survival (effectiveness) was significantly higher in
      the IVUS-guided group (80% vs 69%, p <0.04). In-hospital costs for procedural
      personnel, capital equipment, and disposable equipment were higher in the IVUS
      group. This was offset by lower costs for inpatient care and urgent target vessel
      revascularization in the IVUS group. Therefore, the total in-hospital cost was
      only slightly higher with IVUS (5,245 +/- $2,256 [IVUS] vs 4,776 +/- $2,961
      [ANGIO], $/patient, p = 0.15). During a 2-year follow-up, costs for cardiac
      hospitalizations were slightly lower in the IVUS group, whereas costs for
      medication and indirect costs were similar. This resulted in identical total
      costs over the 2-year period (15,947 +/- $8,545 [IVUS] vs 16,103 +/- $9,954
      [ANGIO], $/patient, p = 0.89). The incremental cost-effectiveness ratio for IVUS
      guidance calculated to -$1,417/major adverse cardiac event-free survival gained.
      In 55.3% of bootstrapping replications, IVUS was less expensive and more
      effective. In conclusion, when used in a provisional stenting strategy, routine
      IVUS imaging is cost-saving half the time.

PMID- 12521625
TI  - Influence of residual stenosis after percutaneous coronary intervention with
      stent implantation on development of restenosis and stent thrombosis.
AB  - The aim of this study was to assess the effects of residual stenosis after single
      stent implantation on the rate of stent thrombosis, as well as restenosis within
      a 6-month follow-up period. Coronary angiograms of 2,157 patients with 2,523
      lesions treated with a single stent were analyzed by quantitative coronary
      angiography before, immediately after stent implantation, and at a planned 6
      month follow-up. Lesions were classified into 4 subgroups according to the degree
      of residual stenosis after stent implantation: group 1, gross oversizing <-15%;
      group 2, slight oversizing -15% to <0%; group 3, mild residual 0% to <15%; group
      4, moderate residual 15% to <30%. Stent thrombosis rates were not significantly
      different among the 4 subgroups (group 1: 0 of 60 [0%]; group 2: 2 of 388 [0.5%];
      group 3: 8 of 1,370 [0.6%]; group 4: 8 of 705 [1.1%]; p = NS for all). An
      adequate dosage of ticlopidine (250 mg twice daily) and aspirin (100 mg/day) led
      to a lower rate of stent thrombosis (6 of 2,189 cases) than inadequate dosages or
      missing therapy (12 of 343 cases). In 1,882 stenoses with angiographic follow-up
      (77.7%), gross oversizing of stents lead to a significantly higher increase of
      percent stenosis (p <0.001) associated with a higher restenosis rate (group 1:
      34.7% vs groups 2, 3, and 4: 32.5%, 28.2%, and 29.6%, respectively). A multiple
      regression analysis was performed. Optimal results with regard to stent
      thrombosis and restenosis were achieved with mild residual stenoses between 0%
      and 15% after stent implantation. Oversizing of stents is no longer necessary
      with an adequate dosage of ticlopidine and aspirin.

PMID- 12521626
TI  - Effect of angiotensin-converting enzyme inhibition on restenosis after coronary
      stenting.
AB  - The Plasma level of angiotensin-converting enzyme (ACE) has been identified as a
      major risk factor for restenosis after coronary stent implantation in selected
      patients; ACE inhibition may therefore contribute to prevent its occurrence. The
      effect of oral ACE inhibition at conventional doses was analyzed retrospectively
      in a series of 897 patients with ischemia who received >or=1 coronary stent on
      998 lesions and underwent angiographic follow-up; no exclusion criteria were
      introduced in this analysis. The restenosis rate in 282 patients (31.4%) taking
      ACE inhibitors was 36.6% compared with 22.9% in 615 non-ACE-inhibited patients (p
      = 0.00001, odds ratio [OR] 1.94, 95% confidence interval [CI] 1.45 to 2.59), and
      the late loss in minimum lumen diameter was 1.25 +/- 0.8 versus 0.96 +/- 0.8 mm,
      respectively (p = 0.0001). During univariate analysis, a negative effect of the
      drug on restenosis was observed in all subgroups of patients (i.e.,
      hypertensives, diabetics, women, and patients with previous myocardial
      infarction). Similar effects were observed independently of the ACE gene
      insertion/deletion polymorphism. During multivariate analysis, ACE inhibition was
      confirmed as an independent risk factor for restenosis (OR 1.84, 95% CI 1.35 to
      2.51, p = 0.0001). Other predictors were the implantation of multiple stents (OR
      2.41, 95% CI 1.60 to 3.64, p <0.0001), diabetes (OR 2.34, 95% CI 1.61 to 3.41, p
      <0.0001), and vessel reference diameter before angioplasty (OR 0.51, 95% CI 0.38
      to 0.69, p <0.0001). Although unexplained and apparently contradictory, our data
      suggest that the use of conventional oral doses of ACE inhibitors in a "real
      world" population who underwent coronary stent implantation increases the
      incidence of in-stent restenosis. Such a finding does not negate the known
      clinical benefits of ACE inhibitors, but it may deserve attention when a patient
      treated with ACE inhibitors becomes a candidate for stent implantation.

PMID- 12521627
TI  - Circumferential mapping and electric isolation of pulmonary veins in patients
      with atrial fibrillation.
AB  - Information about the clinical efficacy and complications of the circumferential
      mapping and isolation of the pulmonary veins (PVs) in patients with atrial
      fibrillation (AF) is still limited. The present study included 75 patients (mean
      age 58 +/- 11 years, 20 women) with paroxysmal (n = 69) or persistent AF (n = 6).
      Mapping of PVs was performed with a circumferential mapping catheter. After
      preferential PV-left atrium (LA) electric inputs were defined, radiofrequency
      ablation was performed until complete isolation of the PVs from the LA was
      achieved. A total of 226 PVs were mapped; 195 (86%) showed typical PV potentials.
      Complete isolation of PVs from the LA was achieved in 173 PVs (89%). Detailed
      follow-up, including 7-day Holter monitoring at 1, 4, 9, and 12 months after
      intervention was performed. If AF reoccurred, PVs were mapped and reisolated.
      After a mean follow-up period of 230 +/- 133 days, 38 of 75 patients (51%) were
      in sinus rhythm. At 1, 4, and 9 months of follow-up, 31 of 65 patients (48%), 36
      of 53 patients (68%, p = 0.04 as compared with the first month), and 21 of 28
      patients (75%, p = 0.025 as compared with the first month), respectively, were in
      sinus rhythm. During follow-up, 30 patients (40%) underwent a second ablation
      procedure due to recurrence. Recurrences were related to resumption of PV muscle
      left atrial conduction (27 patients) and/or extra PV foci (12 patients) or
      nonablated PVs (8 patients). Complications occurred in 17 patients (22%). PV
      stenosis was detected in 13 patients (25% to 50% in 7 patients and >50% in 6
      patients). Pericardial effusion occurred in 4 patients. It was concluded that
      isolation of the PV from the LA is moderately effective in the prevention of AF
      recurrence and could be associated with serious acute and long-term
      complications.

PMID- 12521628
TI  - Impact of serial changes in cardiac hemodynamics on exercise performance in
      patients with heart failure due to ischemic and nonischemic cardiomyopathy.
AB  - Although prior studies have examined the role of central and peripheral
      hemodynamics on exercise tolerance within populations of patients with heart
      failure, a clear relation between hemodynamics and exercise has not been
      demonstrated. This may be due to the inability to control for other factors that
      may influence exercise performance. To isolate the impact of hemodynamics on
      exercise, we studied the relation between changes in these factors within
      individual patients studied on 2 occasions. A consecutive series of 133
      ambulatory patients with heart failure were evaluated on 2 separate occasions
      with right-sided cardiac catheterization and treadmill cardiopulmonary exercise
      testing. Linear regression models were constructed and correlation coefficients
      were determined to examine the relation between changes in hemodynamic variables
      and changes in exercise variables over time for each patient. A significant
      correlation between peak oxygen consumption (VO(2)) and pulmonary arterial wedge
      pressure was found for both the first (r = -0.316, p <0.001) and second (r = 
      0.183, p = 0.029) tests. A stronger inverse correlation between the change in
      pulmonary arterial wedge pressure and change in peak VO(2) was observed in the
      study patients (r = -0.470, p <0.001). Similar correlations were found between
      change in peak VO(2) and changes in pulmonary arterial pressures. Changes in left
      ventricular filling pressure influence exercise tolerance in patients with heart
      failure due to left ventricular systolic dysfunction. Interpretation of
      cardiopulmonary exercise testing for the purpose of determining cardiac
      transplantation eligibility will be improved with knowledge of left ventricular
      filling pressure.

PMID- 12521629
TI  - Clinical outcomes in patients on beta-blocker therapy admitted with worsening
      chronic heart failure.
AB  - Beta blockers have been shown to reduce morbidity and mortality in patients with
      heart failure without evidence of overt congestion. No data are available
      describing outcomes of patients admitted with exacerbated chronic heart failure
      who are receiving beta blockade at the time of admission. The purpose of this
      analysis was to evaluate clinical outcomes in patients from the Outcomes of the
      Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart
      Failure (OPTIME-CHF) study who were prescribed beta blockers on admission
      compared with patients who were not prescribed beta blockers at admission. In
      all, 212 patients were treated with beta blockers at admission and 737 patients
      were not. Baseline characteristics were similar between groups, except that
      patients prescribed beta blockers on admission had slightly higher ejection
      fractions, fewer New York Heart Association class IV symptoms, and lower heart
      rates. There was no difference in clinical events between patients who were
      treated with beta blockers at the time of admission and those who were not.
      Exploratory analyses suggested that patients whose beta-blocker therapy was
      discontinued had a higher risk of adverse outcomes, particularly in the subset of
      patients randomized to milrinone. The data from this nonrandom comparison suggest
      that continuation of pre-existing beta-blocker therapy is not associated with an
      increased risk of adverse clinical events in patients admitted with worsening
      heart failure. These results also suggest that caution should be taken when
      withdrawing beta blockade in this population.

PMID- 12521630
TI  - Detection of mechanisms of immediate failure by transesophageal echocardiography
      in quadrangular resection mitral valve repair technique for severe mitral
      regurgitation.
AB  - Residual mitral regurgitation (MR) after repair is a risk factor for late
      reoperation. The use of intraoperative transesophageal echocardiography (IOTEE)
      decreases the incidence of immediate repair failure. This study identifies the
      mechanisms of immediate failure by IOTEE in the quadrangular resection technique,
      a well-standardized mitral valve repair procedure to guide further repair
      procedures. Two hundred five consecutive patients underwent quadrangular
      resection due to prolapse or flail posterior leaflet. Twenty-four patients (11%)
      had immediate failure. Immediate reinstitution of cardiopulmonary bypass ("second
      pump run") was needed in 21 patients (10%) for further repair. The identified
      mechanisms of failure were residual cleft provoking interscallop malcoaptation
      into the posterior leaflet in 8 patients, residual prolapse of the anterior or
      posterior leaflets in 1 and 4 patients, respectively, residual annular dilation
      in 3, left ventricular outflow obstruction in 2, suture dehiscence in 2, and
      other mechanisms in another 2 patients. In 20 patients (95%), IOTEE guided
      further repair with resolution of the residual MR, whereas 1 patient underwent
      valve replacement due to pharmacologically untreatable left ventricular outflow
      obstruction. In conclusion, even if this type of valve repair technique is well
      standardized, the incidence of immediate failure is not negligible. IOTEE
      identified the mechanisms of the immediate failure and guided further repair
      procedures, thus reducing the incidence of valve replacement (0.5%) without
      increasing perioperative mortality and morbility.

PMID- 12521631
TI  - Deficiency of the vestibular spine in atrioventricular septal defects in human
      fetuses with down syndrome.
AB  - Data on the morphogenesis of atrioventricular septal defect (AVSD) in Down
      syndrome are lacking to support molecular studies on Down syndrome heart critical
      region. Therefore, we studied the development of complete AVSD in human embryos
      and fetuses with trisomy 21 using 3-dimensional graphic reconstructions and
      immunohistochemical markers. Eight trisomic hearts with AVSD and 10 normal
      hearts, ranging from 5 to 16 weeks' gestation, were examined. In AVSD, the
      muscular septum primum and venous valves develop normally, and the size and
      histology of the nonfused endocardial cushions also appear normal. However, the
      mass of extracardiac mesenchyme (vestibular spine), located at the dorsal
      mesocardium, is reduced and does not protrude ventrally along the right wall of
      the common pulmonary vein. As a result of this, the muscular septum primum and
      the right pulmonary ridge are seen as 2 separate septa that attach to the
      inferior endocardial cushion. Both the muscular septum primum and the superiorly
      fused venous valves (septum spurium) converge and are capped by a small rim of
      mesenchyme, which forms the roof of the persisting ostium primum and connects to
      cushions and the reduced vestibular spine. At 7 weeks, ventricular septation in
      AVSD is comparable to 5 to 6 weeks of normal cardiac development. At later
      stages, the septum spurium forms the anterosuperior limbus of the septum secundum
      and the mesenchymal cap becomes the bridging tendon that connects the bridging
      leaflets. Therefore, reduced expansion of the vestibular spine derived from the
      dorsal mesocardium appears to play an important role in the development of AVSD
      in Down syndrome.

PMID- 12521632
TI  - Effect of cutting balloon angioplasty on resistant pulmonary artery stenosis.
AB  - The effectiveness of cutting balloon (CB) therapy was evaluated in severe
      pulmonary artery (PA) stenosis resistant to high-pressure balloon angioplasty in
      children with tetralogy of Fallot and pulmonary atresia. Thirty-eight pulmonary
      vessels (initial diameter 0.4 to 4.0 mm) resistant to high-pressure balloon
      angioplasty, as evidenced by a persistent waist, were treated with CB angioplasty
      in 12 patients. Thirty-two vessels underwent standard CB angioplasty and 6
      vessels were treated with a CB catheter augmenting technique. Of the vessels
      treated with standard CB angioplasty, 17 vessels underwent subsequent high
      pressure balloon angioplasty, 8 vessels had additional high-pressure balloon
      angioplasty and stent placement, and 7 vessels underwent CB dilation alone. The
      diameter of these vessels increased from 1.3 +/- 0.7 to 2.8 +/- 0.9 mm (p
      <0.001). Six of the 38 vessels were treated with a CB catheter augmenting
      technique; these vessels were larger with an initial diameter of 2.6 +/- 0.8 mm
      and increased to 4.4 +/- 1.7 mm (p <0.001). Of the 38 vessels, 35 increased by
      >50%, for a procedural success rate of 92%. Intimal damage was angiographically
      evident in 17 of 38 vessels (45%) after CB angioplasty; 1 procedure was
      complicated by an unconfined tear requiring coil occlusion of the distal vessel
      and another resulted in a confined tear, successfully managed with stent
      implantation. This study supports prior reports of successful angioplasty with CB
      therapy for resistant PA stenosis, identifies potential complications, and
      expands the experience to infants, larger vessels, and sublobar locations.

PMID- 12521633
TI  - Long-term cardiorespiratory results of exercise training following cardiac
      transplantation.
AB  - The long-term influence of exercise training after heart transplantation remains
      unclear. Accordingly, we performed a 12-year follow-up study of 36 patients who
      underwent heart transplantation. Findings for survivors were compared with those
      of age-matched controls over the same period. Comparisons were also made between
      survivors and deceased patients. The sample comprised 36 men (aged 47 +/- 9
      years) and a group of healthy age-matched controls. The patients received 16
      months of outpatient exercise training; physiologic data were collected initially
      and at discharge. At 12 years, further data were collected on 20 of 23 survivors
      and their controls; 3 of the survivors were unavailable for final assessment, and
      13 patients had died in the interim. The survivors' peak oxygen intake
      (V*O(2peak)) increased 26% after training and decreased 0.39 mlkg(-1)min(-1) per
      year (27.9 +/- 7 to 23.7 +/- 6), which was a similar rate as the controls (0.37
      mlkg(-1)min(-1) per year; 33.7 +/- 7 to 29.2 +/- 7). Lean body mass (LBM)
      increased 3 kg by 16 months and a further 2.5 kg by 12 years, but ultimately was
      3 kg below the controls. Although there was no difference in entry data between
      deceased patients and survivors, the latter attained greater gains in V*O(2peak)
      and LBM over the 16 months of training. Thus, in heart transplantation patients
      who undergo training, gains in exercise capacity are lost over 12 years at a rate
      commensurate with normal aging. A reduced training response in V*O(2peak) and LBM
      contributes to a poorer prognosis.

PMID- 12521634
TI  - Comparison of aortic elasticity determined by cardiovascular magnetic resonance
      imaging in obese versus lean adults.
AB  - The vascular properties of large vessels in the obese have not been adequately
      studied. We used cardiovascular magnetic resonance imaging to quantify the cross
      sectional area and elastic properties of the ascending thoracic and abdominal
      aorta in 21 clinically healthy obese young adult men and 25 men who were age
      matched lean controls. Obese subjects had greater maximal cross-sectional area of
      the ascending thoracic aorta (984 +/- 252 vs 786 +/- 109 mm(2), p <0.01) and of
      the abdominal aorta (415 +/- 71 vs 374 +/- 51 mm(2), p <0.05). When indexed for
      height the differences persisted, but when indexed for body surface area, a
      significant difference between groups was found only for the maximal abdominal
      aortic cross-sectional area. The obese subjects also had decreased abdominal
      aortic elasticity, characterized by 24% lower compliance (0.0017 +/- 0.0004 vs
      0.0021 +/- 0.0005 mm(2)/kPa/mm, p <0.01), 22% higher stiffness index beta (6.0 +/
      1.5 vs 4.9 +/- 0.7, p <0.005), and 41% greater pressure-strain elastic modulus
      (72 +/- 25 vs 51 +/- 9, p <0.005). At the ascending thoracic aorta, only the
      pressure-strain elastic modulus was different between obese and lean subjects (85
      +/- 42 vs 65 +/- 26 kPa, respectively; p <0.05), corresponding to a 31%
      difference-but arterial compliance and stiffness index were not significantly
      different between groups. In clinically healthy young adult obese men, obesity is
      associated with increased cross-sectional aortic area and decreased aortic
      elasticity.

PMID- 12521635
TI  - Role of C-reactive protein in the assessment of cardiovascular risk.

PMID- 12521636
TI  - George Allan Beller, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 12521637
TI  - Frequency, characteristics, and outcome of patients hospitalized with acute
      coronary syndromes with undetermined electrocardiographic patterns.

PMID- 12521638
TI  - Facilitated percutaneous coronary intervention in patients with acute myocardial
      infarction transferred from remote hospitals.

PMID- 12521639
TI  - Relation of erectile dysfunction to angiographic coronary artery disease.

PMID- 12521640
TI  - Usefulness of atrial fibrillation as a marker of outcome after percutaneous
      coronary intervention.

PMID- 12521641
TI  - Outcome in patients treated with primary angioplasty for acute myocardial
      infarction due to left main coronary artery occlusion.

PMID- 12521643
TI  - Influence of native conduction status on clinical results with right ventricular
      outflow tract pacing.

PMID- 12521642
TI  - Frequency of creatine kinase elevation during treatment with fluvastatin in
      combination with fibrates (bezafibrate, fenofibrate, or gemfibrozil).

PMID- 12521644
TI  - Long-term prognostic significance of complex ventricular arrhythmias induced
      during dobutamine stress echocardiography.

PMID- 12521645
TI  - Neurohormonal prediction of mortality following admission for decompensated heart
      failure.

PMID- 12521646
TI  - Compression of pulmonary veins between the left atrium and the descending aorta.

PMID- 12521647
TI  - Effect of hormonal replacement therapy on C-reactive protein and cell-adhesion
      molecules in postmenopausal women.

PMID- 12521648
TI  - Influence of age on assessment of diastolic function by Doppler tissue imaging.

PMID- 12521649
TI  - Expression of an atherogenic dyslipidemic phenotype in the postprandial period.

PMID- 12521650
TI  - Amenorrhea associated with contraception-an international study on acceptability.
AB  - Surveys undertaken in the 1970s and 1980s suggested that amenorrhea was
      unacceptable to most women, especially in developing countries. More recent
      research suggests that increasing numbers of women in the developed world prefer
      to menstruate less often. In a questionnaire survey of 1001 women attending
      family-planning clinics and 290 contraceptive providers in China, South Africa,
      Nigeria and Scotland, only among black women in Africa did the majority like
      having periods. In all other groups, most women disliked periods, which were
      "inconvenient" and associated with menstrual problems. Given the choice, the
      majority of Nigerian women would prefer to bleed monthly. Elsewhere, women would
      opt to bleed only once every 3 months, or not at all. In all except the Chinese
      centers, the majority of women would be willing to try a contraceptive which
      induced amenorrhea. Providers tended to overestimate the importance of regular
      menstruation to their clients. This is an important observation for scientists
      and funding agencies involved in developing new methods of contraception.

PMID- 12521652
TI  - Sponge versus diaphragm for contraception: a Cochrane review.
AB  - The contraceptive vaginal sponge was developed as an alternative to the
      contraceptive diaphragm. Unlike the diaphragm, the sponge can be used for more
      than one coital act within 24 h without the insertion of additional spermicide,
      and it does not require fitting or a prescription from a physician. We conducted
      a systematic review of randomized controlled trials that compared the vaginal
      contraceptive sponge with the diaphragm used with a spermicide in order to
      evaluate the efficacy and continuation rates of the two devices. The sponge was
      statistically significantly less effective in preventing overall pregnancy than
      was the diaphragm in the two trials that met our inclusion criteria. The 12-month
      cumulative life table termination rates per 100 women for overall pregnancy were
      17.4 for the sponge versus 12.8 for the diaphragm in the larger US trial, and
      24.5 for the sponge and 10.9 for the diaphragm in the UK trial. Similarly,
      discontinuation rates at 12 months were higher with the sponge than with the
      diaphragm [odds ratio 1.3; 95% confidence interval (CI) 1.1-1.6]. Allergic-type
      reactions were more common with the sponge in both trials, although the frequency
      of discontinuation for discomfort differed in the two trials. Other randomized
      controlled trials will be needed to resolve the role of spermicides in preventing
      sexually transmitted infections or in causing adverse effects.

PMID- 12521651
TI  - Bleeding patterns and patient acceptability of standard or continuous dosing
      regimens of a low-dose oral contraceptive: a randomized trial.
AB  - The purpose of this study is to compare bleeding patterns and acceptability of a
      contraceptive regimen of combined 20 microg ethinyl estradiol/100 microg
      levonorgestrel taken with and without a hormone-free interval. Thirty-two women
      desiring oral contraception were randomized to six 28-day cycles (standard group)
      or 168 days without a pill-free interval (continuous group). Participants kept a
      daily bleeding calendar documenting bleeding events (none, spotting or required
      sanitary protection) and side effects (headache, nausea, breast tenderness,
      depression, premenstrual syndrome and bloating). Primary outcome was number of
      bleeding days. Secondary outcomes included bleeding days requiring sanitary
      protection, amenorrhea, patient acceptability of bleeding patterns, method
      satisfaction and affective side effects. There were no differences in the
      baseline characteristics of the two groups. Although total bleeding days were
      fewer in the continuous group (mean = 25.9 vs. 34.9 days), this result did not
      reach statistical significance. However, women in the continuous group reported
      significantly fewer bleeding days that required protection (18.4 vs. 33.8 days, p
      < 0.01), and were more likely to have amenorrhea. Although both groups reported a
      high level of satisfaction with bleeding patterns and side effect profiles, women
      in the continuous group reported significantly fewer days of bloating (0.7 vs.
      11.1 days, p = 0.04), and menstrual pain (1.9 vs. 13.3 days, p < 0.01).
      Continuous use of 20 microg ethinyl estradiol/100 microg levonorgestrel is
      associated with less bleeding requiring protection, and more amenorrhea than
      standard administration. Taken with or without a hormone-free interval, this oral
      contraceptive formulation is highly acceptable with regard to bleeding patterns
      and side effect profile. The continuous group had fewer light and moderate
      bleeding days, less bloating and menstrual pain. For patients who are seeking
      these results, this method may be more desirable.

PMID- 12521653
TI  - Oral contraceptives: a risk factor for uncontrolled blood pressure among
      hypertensive women.
AB  - The objective of the study was to assess the association between systolic and
      diastolic blood pressure (SBP and DBP) and the use of oral contraceptives (OC) in
      hypertensive women. In a prospective cross-sectional study, we evaluated 171
      women who were referred to the Hypertension Outpatient Clinic of Hospital de
      Clinicas de Porto Alegre; 66 current users of OC, 26 users of other contraceptive
      methods and 79 women who were not using contraception. The average of six blood
      pressure readings was used to establish the usual blood pressure of the
      participants. Current OC users were compared with users of other methods and with
      patients not using contraception. Main outcome measures were SBP and DBP among
      the different groups, and prevalence of uncontrolled hypertension (SBP >or= 140
      mmHg and DBP >or= 90 mmHg). DBP was higher in OC users (100.2 +/- 15.9 mmHg) than
      in patients using other contraceptive methods (93.4 +/- 14.7 mmHg) and not using
      contraceptives (93.3 +/- 14.4 mmHg, p = 0.016). Women using OC for more than 8
      years presented higher age-adjusted blood pressure levels than women using OC for
      shorter periods. Patients using OC had poor blood pressure control (p for trend =
      0.046) and a higher proportion of them presented moderate-severe hypertension.
      These results were independent of antihypertensive drug use. In a logistic
      regression model, we found that current OC use was independently and
      significantly associated with prevalence of uncontrolled hypertension. It is
      concluded that hypertensive women using OC present a significant increase in DBP
      and poor blood pressure control, independent of age, weight and antihypertensive
      drug treatment.

PMID- 12521654
TI  - Effect of four different oral contraceptives on various sex hormones and serum
      binding globulins.
AB  - In a double-blind, controlled, randomized, four-arm, bicentric clinical study,
      the effect of four oral contraceptives (OCs) on various hormone parameters and
      serum-binding globulins was investigated. Four groups with 25 volunteers each (18
      35 years of age) were treated for six cycles with monophasic combinations
      containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg
      dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2
      mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg
      levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood
      samples were taken after at least 12 h of fasting on Day 21-26 of the preceding
      control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The
      serum concentrations of free testosterone were significantly decreased by about
      40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS)
      showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which
      increased prolactin significantly during the third and sixth cycles, no change
      was observed with the EE-containing preparations. There was a significant
      increase in the levels of serum-binding globulins during treatment, which
      differed according to the composition of the OCs used. The rise in sex hormone
      binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest
      with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar
      (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by
      50-60%, during treatment with the DNG-containing formulations, while the effect
      of EE/LNG was less significant (+30%). The rise in corticosteroid-binding
      globulin (CBG), which occurred in all groups, was most pronounced in women
      treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong
      influence of EE and no effect of the progestogen component. In all treatment
      groups, the frequency of intracyclic bleeding rose in the first treatment cycle
      and decreased thereafter. Cycle control was significantly better with 30EE/DNG or
      EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood
      pressure, body mass index or pulse rate throughout the study. In conclusion, the
      DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG
      containing preparation. The effects on CBG suggest a lesser hepatic effect of 2
      mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol
      in OCs appeared to increase prolactin release, while the cycle control was better
      with the OC containing 30 microg EE.

PMID- 12521655
TI  - Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral
      contraceptive use in young women.
AB  - With the aim to determine whether bone metabolism in young women using low-dose
      oral contraception is influenced by vitamin D receptor (VDR) genotype, we
      designed the prospective clinical study of 41 healthy women aged 20-27 years.
      Twenty-one women of the study group were prescribed an oral contraceptive (30
      microg ethynyl estradiol and 150 microg levonorgestrel) and 20 women of the
      control group a nonhormonal contraceptive or none. Biochemical markers of bone
      metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline)
      and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the
      study group, the BB genotype subgroup showed significantly decreased osteocalcin
      (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p =
      0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no
      changes were observed. In the control group, there were no significant changes in
      markers of bone metabolism regarding VDR genotype. In conclusion, our study shows
      that in young women VDR gene polymorphism could influence bone metabolism during
      low-dose oral contraceptive use.

PMID- 12521656
TI  - Emergency contraception: from accessibility to counseling.
AB  - Since emergency contraception (EC) users have a higher risk sexual profile, they
      may miss an opportunity for medical counseling if getting EC directly from a
      pharmacy. However, direct access to emergency contraception through pharmacies
      has been shown to increase EC use. Informational materials destined for EC users
      could alert women to the importance to check for sexually-transmitted infections
      considering health issues related to STDs.

PMID- 12521657
TI  - Quality of life following early medical or surgical abortion.
AB  - Short-term quality of life following abortion is poorly characterized. We
      conducted a prospective cohort study to evaluate 97 U.S. women who selected
      either medical abortion with mifepristone and misoprostol or surgical abortion up
      to 9 weeks gestation in a private-practice setting. Women choosing medical
      abortion and those choosing surgical abortion with local anesthesia were similar
      on most baseline characteristics. Eighty-five participants completed a
      standardized quality of life assessments three times over 1 month. The 30-item
      questionnaire yielded scores for global health, emotional, social, cognitive and
      physical functioning and for specific symptom scales. At baseline, participants
      reported many symptoms and functional limitations during the previous week.
      Subjects in both treatment groups experienced clinically and statistically
      significant improvements on all scales at follow-up. Surgical abortion patients
      had worse scores on three of five function scales and several symptom scales at
      baseline compared to medical abortion patients. Differences in baseline scores
      between the medical and surgical abortion patients disappeared during follow-up.
      A surprising finding was that partner knowledge of the pregnancy at the time the
      abortion appointment was made was associated with significantly worse scores on
      most of the function and symptom scales. These results provide substantial
      reassurance that women undergoing abortion experience a marked improvement in
      their quality of life after the abortion. Women choosing medical or surgical
      abortion report very similar quality of life improvements.

PMID- 12521658
TI  - Cannula fracture in first trimester abortion: a case report and survey of NAF
      providers.
AB  - Complications in first trimester surgical abortions are uncommon. These include
      retained products of conception, infection, hemorrhage, perforation and
      hematometria. We report a case of a plastic cannula fracture. This event prompted
      further investigation of this issue and the factors that might increase the
      likelihood of its occurrence. We investigated whether the recycling of disposable
      cannulas may increase the frequency of cannula fracture. National Abortion
      Federation Members (NAF) were surveyed by mail. These providers were asked to
      comment anonymously on their experience with first trimester surgical abortions,
      resterilization of plastic cannulas and cannula fracture. The response rate was
      71% after three mailings. The overall proportion of providers reporting previous
      cannula fractures was 9%. The rate of resterilization and reuse was 10%. Cannula
      resterilization did not significantly increase the likelihood of a fracture (p =
      0.25). Cannula fracture is a rare complication of first trimester surgical
      abortion. Cannula fracture was not found to be associated with resterilization.

PMID- 12521659
TI  - Uterine perforation on intrauterine device insertion: is the incidence higher
      than previously reported?
AB  - The objective of the study was to determine the rate of uterine perforation
      associated with insertion of Multiload Cu375 in 'real-life' clinical use. It was
      a prospective observational cohort study using Prescription Event Monitoring
      methodology. There were 17,469 Multiload Cu375 insertions in 16,159 women between
      1991 and 2001. The insertions were performed by 1,699 different doctors (mostly
      general practitioners) in surgeries, clinics, and hospitals throughout New
      Zealand. The results found 28 reports suggesting complete or partial uterine
      perforation, giving an incidence of 1.6 per 1000 insertions. Most perforations
      (86%) were not diagnosed at the time of insertion, with some remaining
      undiagnosed for several years. Doctors who reported inserting fewer than 10
      Multiload Cu375 devices in the study period reported significantly more
      perforations than doctors who reported inserting between 10 and 100 devices did.
      In conclusion, we found the perforation rate in this study is higher than in
      clinical trials of Multiload Cu375. This might be because of inclusion of partial
      perforations in this study, a longer follow-up period, the large number of
      insertions studied, or because the majority of inserting doctors were less
      experienced than inserters in other studies.

PMID- 12521660
TI  - Effect of temperature and pH on contraceptive gel viscosity.
AB  - The rheological properties of four commercially available spermicidal gels (two
      polyacrylic acid derivatives and two carboxymethylcellulose based) and their
      dilutions with a vaginal fluid simulant (pH 4.2) and a semen simulant (pH 7.7)
      were measured at 25 degrees C and 37 degrees C over a biologically relevant range
      of shear rates. All four gels were shear thinning with temperature-dependent
      rheological properties. The two types of gels responded differently to dilution.
      The rheological properties of the polyacrylic acid derivative gels were strongly
      dependent on the type of diluent used. Their viscosities after dilution with the
      semen simulant were 100 times greater than after comparable dilutions with the
      vaginal fluid simulant, this effect being due primarily to the higher pH. The
      cellulose gels did not exhibit such an effect. These results suggest that the
      polyacrylic acid and cellulose gels interact differently with the vaginal
      environment in vivo. Such differences could lead to differences in the extent and
      durability of epithelial coating.

PMID- 12521661
TI  - Structural integrity of the polyurethane female condom after multiple cycles of
      disinfection, washing, drying and relubrication.
AB  - The female condom provides an important alternative means of protection against
      HIV and other sexually transmitted infections for women, particularly in
      situations where partners are reluctant or refuse to use male condoms. The
      relatively high cost of the device, however, is a barrier to its use in resource
      poor environments. This has led to some reuse of the product and two studies have
      demonstrated that female condoms can withstand a limited level of reuse without
      an excessive loss of structural integrity when washed with soap and water. A
      consultation on female condom reuse convened by the World Health Organization and
      the Joint United Nations Programme on AIDS in June 2000 recommended that all used
      female condoms should be disinfected immediately after use, before washing. The
      effect of such treatments on the female condom was not known. This study was
      undertaken to assess the effect of the disinfection, washing, drying and
      relubrication on the properties of the condom. Samples from three batches of
      female condoms were subjected to seven treatment cycles before being tested for
      structural integrity. In all cases the batches of condoms complied with the
      manufacturer's release specification for the product after treatment. Some minor
      changes in properties were seen but these were not considered important. There
      was evidence of a small increase in the number of condoms with holes following
      repeated disinfection and washing cycles, suggesting that excessive or rough
      handling can damage the condom. Condoms should therefore be handled carefully and
      inspected thoroughly for signs of damage after washing and drying before being
      stored with the intention of subsequently reusing the device.

PMID- 12521662
TI  - A short-term evaluation of semen and accessory sex gland function in phase III
      trial subjects receiving intravasal contraceptive RISUG.
AB  - Following the intravasal injection of a new male contraceptive RISUG (reversible
      inhibition of sperm under guidance) in volunteers, routine semen analysis, semen
      biochemistry and germ cell morphology were evaluated in comparison with the
      corresponding preinjection samples for a maximum period of 6 months. Sperm counts
      in all 25 subjects before injection varied from 45 to 120 x 10(6)/ml. Out of 25
      subjects, 6 became azoospermic after 1 month, 15 after 2 months, 3 after 3 months
      and 1 after 4 months of contraceptive injection. The mean volume of the
      ejaculates was found to be less as compared to preinjection samples. Occasional
      sperm or sperm heads and immature germ cells were identified in only a few
      postinjected subjects. However, no pregnancy was reported in these subjects
      during the study period. Abnormal morphology found in most of the sperm, but not
      in the accompanying immature germ cells, may be due to a charge-related effect on
      the former but not on the latter cells. Neutral alpha-glucosidase, the
      biochemical marker for epididymis, was estimated to be significantly lower in the
      seminal plasma of all the postinjected subjects. On the other hand, acid
      phosphatase activity and fructose levels in the seminal plasma were found to be
      in the normal range. Based on the above findings, it is concluded that at least
      for the present study period, RISUG, a new male contraceptive, is effective as a
      partially occluding agent in the vas deferens.

PMID- 12521663
TI  - Horse-race model simulations of the stop-signal procedure.
AB  - In the stop-signal paradigm, subjects perform a standard two-choice reaction task
      in which, occasionally and unpredictably, a stop-signal is presented requiring
      the inhibition of the response to the choice signal. The stop-signal paradigm has
      been successfully applied to assess the ability to inhibit under a wide range of
      experimental conditions and in various populations. The current study presents a
      set of evidence-based guidelines for using the stop-signal paradigm. The evidence
      was derived from a series of simulations aimed at (a) examining the effects of
      experimental design features on inhibition indices, and (b) testing the
      assumptions of the horse-race model that underlies the stop-signal paradigm. The
      simulations indicate that, under most conditions, the latency, but not
      variability, of response inhibition can be reliably estimated.

PMID- 12521664
TI  - The influence of irrelevant stimulus changes on stimulus and response repetition
      effects.
AB  - In this study the influence of irrelevant stimulus changes from one trial to
      another in a serial reaction time task was investigated. Two experiments were
      performed in which subjects were required to respond to stimulus colour. Four
      colours were mapped on two response keys, so that colour and response repetition
      effects could be dissociated. In Experiment 1, the irrelevant stimulus dimension
      was location and in Experiment 2 it was shape. Both experiments were performed
      with a short and a long response-stimulus interval (RSI)-condition. In both
      experiments, the irrelevant dimension influenced the response repetition effect
      but not the colour repetition effect. In the reaction times, a response
      alternation effect was observed only when the irrelevant location of the stimulus
      changed in the long RSI-condition. The error rates showed a response alternation
      benefit for both irrelevant dimensions, in the short and the long RSI-condition.
      The benefit for response alternations is explained in terms of a response bias
      towards change that is triggered by a changing stimulus feature. We assume that
      the response bias is stronger for location than for colour and that accuracy is
      more sensitive to this bias than response latencies.

PMID- 12521665
TI  - On spatial response code activation in a Simon task.
AB  - The Simon effect refers to the performance advantage for trials where the task
      irrelevant location of a target spatially corresponds with the location of the
      response. It is thought that the irrelevant spatial code of the target
      facilitates responding by automatically pre-activating the spatially
      corresponding response code. This spatial code is thought to passively decay
      shortly after its activation. In this investigation, the response was selected
      according to the identity of a central cue. The selected response was executed or
      withheld depending the identity (Experiment 1) or the presence (Experiment 2) of
      the target. Varying the stimulus-onset asynchrony (SOA), between the central
      response cue and the peripheral target, allowed for a time-course analysis of the
      Simon effect. The results of two experiments provided no indication that the
      activation level of the irrelevant spatial code decayed while the relevant
      response was prepared. Although reaction times increased as the SOA decreased,
      the Simon effect was additive with SOA, suggesting that the automatic activation
      of the task-irrelevant spatial code was delayed until the task-relevant response
      code was mostly prepared, perhaps due to the capacity limitations of response
      selection.

PMID- 12521666
TI  - Using Brunswikian theory and a longitudinal design to study how hierarchical
      teams adapt to increasing levels of time pressure.
AB  - Brunswikian theory and a longitudinal design were used to study how three-person,
      hierarchical teams adapted to increasing levels of time pressure and, thereby,
      try to understand why previous team research has not necessarily found a direct
      relationship between team processes and performance with increasing time
      pressure. We obtained four principal findings. First, team members initially
      adapted to increasing time pressure without showing any performance decrements by
      accelerating their cognitive processing, increasing the amount of their implicit
      coordination by sending more information without being asked and, to a lesser
      extent, filtering (omitting) certain activities. Second, teams began and
      continued to perform the task differently with increasing time pressure, yet
      often achieved comparable levels of performance. Third, time pressure did affect
      performance because there was a level of time pressure beyond which performance
      could not be maintained, although that level differed for different teams. And,
      fourth, some adaptation strategies were more effective than others at the highest
      time pressure level. Taken together, these findings support the Brunswikian
      perspective that one should not necessarily expect a direct relationship between
      team processes and performance with increasing time pressure because teams adapt
      their processes in different, yet often equally effective ways, in an effort to
      maintain high and stable performance.

PMID- 12521667
TI  - Decision making under internal uncertainty: the case of multiple-choice tests
      with different scoring rules.
AB  - This paper assesses framing effects on decision making with internal uncertainty,
      i.e., partial knowledge, by focusing on examinees' behavior in multiple-choice
      (MC) tests with different scoring rules. In two experiments participants answered
      a general-knowledge MC test that consisted of 34 solvable and 6 unsolvable items.
      Experiment 1 studied two scoring rules involving Positive (only gains) and
      Negative (only losses) scores. Although answering all items was the dominating
      strategy for both rules, the results revealed a greater tendency to answer under
      the Negative scoring rule. These results are in line with the predictions derived
      from Prospect Theory (PT) [Econometrica 47 (1979) 263]. The second experiment
      studied two scoring rules, which allowed respondents to exhibit partial
      knowledge. Under the Inclusion-scoring rule the respondents mark all answers that
      could be correct, and under the Exclusion-scoring rule they exclude all answers
      that might be incorrect. As predicted by PT, respondents took more risks under
      the Inclusion rule than under the Exclusion rule. The results illustrate that the
      basic process that underlies choice behavior under internal uncertainty and
      especially the effect of framing is similar to the process of choice under
      external uncertainty and can be described quite accurately by PT.

PMID- 12521668
TI  - Diabetes mellitus and 2,3,7,8-tetrachlorodibenzo-p-dioxin elimination in veterans
      of Operation Ranch Hand.
AB  - Using multivariate statistical models, no significant relationship was found
      between the rate of 2,3,7,8-tetrachlorodibenzo-p-dioxin ( TCDD) elimination and
      the occurrence or time to onset of diabetes in 343 veterans of Operation Ranch
      Hand, the unit responsible for the aerial spraying of Agent Orange and other TCDD
      contaminated herbicides during the Vietnam War. Without adjustment for age, body
      mass index, family history of diabetes, and smoking history, the time to onset of
      diabetes decreased and the risk of diabetes increased with a diminished
      elimination rate. However, after adjustment, diabetes time to onset and
      occurrence were not significantly associated with TCDD elimination. Analyses of
      covariance found no significant difference between the average elimination rates
      of diabetic and nondiabetic veterans, without or with adjustment for risk
      factors. To our knowledge, this is the only study to date to examine TCDD
      elimination and diabetes.

PMID- 12521669
TI  - N-acetylcysteine pretreatment decreases cocaine and endotoxin-induced
      hepatotoxicity.
AB  - Cocaine produces hepatotoxicity by a mechanism that remains undefined but has
      been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is
      also a well-known cause of hepatic damage, and exposure to noninjurious doses of
      LPS increases the toxicity of certain hepatotoxins. Previously it was
      demonstrated that exposure to noninjurious doses of LPS dramatically increases
      cocaine-mediated hepatotoxicity (CMH). This study was conducted to investigate
      whether pretreatment with N-acetylcysteine (NAC), a glutathione (GSH) precursor
      and an antioxidant agent, inhibits LPS potentiation of CMH. For 5 consecutive
      days, male CF-1 mice were administered daily oral NAC (200 mg/kg) or sterile
      saline followed an hour later by cocaine (20 mg/kg) or sterile saline. Four hours
      following the last cocaine or saline treatment, the mice were administered 12 x
      10(6) EU LPS/kg or sterile saline. For the cocaine alone and cocaine and LPS
      groups, NAC pretreatment significantly decreased serum alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) activities with absence of necrotic
      hepatic lesions, indicating a reduction of liver injury. In addition, in all
      groups pretreated with NAC, hepatic GSH concentration was significantly
      increased, as were hepatic and blood glutathione peroxidase (GPx) and catalase
      (CAT) activities. In conclusion, the results demonstrate that NAC pretreatment
      exerted a protective effect against LPS potentia-tion of CMH.

PMID- 12521670
TI  - Reduction of tissue concentration of cocaine in rat by ketamine.
AB  - The coabuse of cocaine and ketamine occurs with high frequency. The presence of
      another active substance with cocaine allows for the potential of various drug
      drug interactions to occur. This study investigated the tissue distribution after
      the administration of cocaine or ketamine alone and their combination in rat.
      Cocaine (5 mg/kg iv), ketamine (100 mg/kg by gavage), or ketamine followed by
      cocaine (same doses and routes of administration) was utilized. Tissue contents
      of cocaine and norcocaine were significantly lowered at 5, 15, and 30 min
      following ketamine administration versus cocaine alone. However, tissue contents
      of benzoylecgonine were significantly higher in the combination group compared to
      cocaine alone. On the other hand, cocaine administration did not affect the
      tissue disposition of ketamine. The results suggest that ketamine decreased
      cocaine tissue content, which may affect its pharmacological and toxicological
      profiles.

PMID- 12521671
TI  - A physiologically based pharmacokinetic model for acrylamide and its metabolite,
      glycidamide, in the rat.
AB  - Acrylamide is a neurotoxicant and a multisite carcinogen in rats following
      chronic, high-dose exposures. In an effort to improve risk-based decisions for
      acrylamide (AMD) and its epoxide metabolite, glycidamide (GLY), a physiologically
      based pharmacokinetic (PBPK) model was developed for describing AMD and GLY
      kinetics in the rat. The PBPK model consists of components for both AMD and GLY.
      AMD is distributed within five compartments (arterial blood, venous blood, liver,
      lung, and all other tissues lumped together) and is linked to the GLY portion of
      the model via metabolism in the liver. GLY is distributed within the same five
      compartments. Dosing of AMD via the intravenous, intraperitoneal, or oral route
      of exposure is incorporated into the model structure. The model parameters
      include measured values for rat physiology (tissue volumes, blood flows),
      estimated tissue partition coefficients based on a published algorithm, and
      estimated values for metabolism and tissue binding based on fitting the model to
      tissue kinetic data from four studies. Despite gaps and limitations in the
      available database, a reliable description of the kinetics of AMD and GLY from
      existing studies was obtained using a single set of model parameters. The
      metabolism of AMD via cytochrome P-450 was best described using a Vmax of 1.6
      mg/h/kg and a Km of 10 mg/L, while the metabolism of AMD via GST was described
      using a second-order rate constant of 0.55 L/h-mmol GSH. Similarly, the
      metabolism of GLY via epoxide hydrolase was best described using a Vmax of 1.9
      mg/h/kg and a Km of 100 mg/L, while the metabolism of GLY via GST was described
      using a rate constant of 0.8 L/h-mmol GSH. These parameters were established
      based on the proportion of various metabolites found in urine. Future studies
      will need to focus on the collection of key data for refining model parameters
      for metabolism and tissue binding and for model validation, as well as for
      developing a similar model for humans. Completion of these additional studies
      will result in a validated rat and human PBPK model capable of predicting tissue
      doses linked to potential mechanisms of toxic effects for AMD and GLY and allow
      determination of scientifically defensible exposure limits that remain protective
      of human health.

PMID- 12521672
TI  - Effects of gestational exposure to chlorpyrifos on postnatal central and
      peripheral cholinergic neurochemistry.
AB  - The effects of gestational exposure to the commonly used organophosphorus
      insecticide chlorpyrifos (O,O-diethyl O-[3,5,6-trichloro-2
      pyridinyl]phosphorothioate) on postnatal central and peripheral cholinergic
      neurochemistry were investigated. Pregnant rats were orally dosed daily with
      chlorpyrifos (0, 3, 5, or 7 mg/kg) in corn oil from gestation day 6 to 20. Pups
      were sacrificed on postnatal days 1, 3, 6, 9, and 12 for the determination of
      brain, heart, lung, and serum cholinesterase, and brain choline acetyltransferase
      activities, along with liver carboxylesterase activity. Exposure to chlorpyrifos
      did not produce signs of overt toxicity to the dams or developing offspring.
      Cholinesterase activities were inhibited in a dose-related manner, with brain
      cholin-esterase inhibition of about 26%, 32%, and 45% on postnatal day 1.
      Inhibition of brain cholineste-rase persisted in all treatment groups until
      postnatal day 6 and in the medium and high-dosage groups through postnatal day 9.
      Liver carboxylesterase activity was also inhibited in a dose-related manner, with
      a recovery profile parallel to that of brain cholinesterase. Choline
      acetyltransferase activity was decreased by about 13% in the high-dosage group on
      postnatal days 9 and 12. These results indicate that gestational exposure to
      chlorpyrifos results in relatively persistent inhibition of brain cholinesterase
      and a delayed depression of choline acetyltransferase at a time when brain
      cholinesterase activity had returned to control levels in the high-dosage group.

PMID- 12521676
TI  - Labour induction with alternative drugs?

PMID- 12521673
TI  - Influence of gender on thermoregulation and cholinesterase inhibition in the long
      evans rat exposed to diazinon.
AB  - Diazinon is an organophosphate (OP)-based, anticholinesterase insecticide that
      irreversibly inhibits acetylcholinesterase activity and produces cholinergic
      stimulation in central nervous system (CNS) and peripheral tissues. Our
      laboratory has found that OPs administered orally in rats induce a transient
      period of hypothermia followed by a delayed fever that persists for several days
      after exposure. There is little information on the thermoregulatory effects of
      diazinon. Core temperature (Tc) and motor activity (MA) were monitored by
      radiotelemetry in male and female rats of the Long-Evans strain dosed orally with
      diazinon (0 [corn-oil vehicle], 100, 200, or 300 mg/kg in males and 0, 50, 100,
      or 200 mg/kg in females). There was a dose-dependent decrease in Tc during the
      first night after treatment, with females exhibiting slightly greater sensitivity
      than males. MA was unaffected in females exposed to diazinon at doses of 50 to
      200 mg/kg; MA of males was reduced during the first night after dosing with 300
      mg/kg. There was a delayed elevation in Tc of males dosed with 200 and 300 mg/kg
      and females dosed with 50, 100, and 200 mg/kg diazinon. The elevated Tc was only
      manifested during d 2 and 3 after diazinon. Administration of 200 mg/kg sodium
      salicylate to females 48 h after being treated with 200 mg/kg diazinon led to a
      rapid abatement of the fever. Diazinon doses of 50 to 300 mg/kg led to 40% to 50%
      inhibition in plasma cholinesterase (ChE) activity 4 h after dosing, and females
      displayed a significantly slower recovery of ChE activity compared to males. When
      compared on a molar basis, the hypothermic response to diazinon was relatively
      small compared to other OPs such as chlorpyrifos. The delayed fever and efficacy
      of sodium salicylate to block diazinon-induced fever are similar to the effects
      of OPs chlorpyrifos and diisopropyl fluoro-phosphate (DFP).

PMID- 12521690
TI  - Secondary postpartum haemorrhage.

PMID- 12521691
TI  - Antibodies to oxidised low-density lipoproteins and cardiolipin in pre-eclampsia
      and eclampsia.
AB  - The objective of this study was to test the hypothesis that autoantibodies to
      phospholipids and to oxidised low-density lipoprotein (ox-LDL) are increased in
      pre-eclamptic and eclamptic women compared with normal pregnancy. Serum
      concentrations of autoantibodies to ox-LDL and to cardiolipin were measured in 21
      non-pregnant controls, 29 pregnant controls, 21 pre-eclamptic and six eclamptic
      women. Concentrations of IgG antibodies to ox-LDL and to cardiolipin were not
      significantly different in women with eclampsia as compared with the non-pregnant
      controls, pregnant controls and pre-eclampsia. Concentrations of IgM antibodies
      to cardiolipin were significantly lower in women with pre-eclampsia compared with
      non-pregnant controls and eclampsia. All three pregnant states differ markedly
      from the non-pregnant controls, of whom only 5% (1 of 21) had "high positive" IgG
      antibodies. These results suggest that ACAs rise as a result of the pregnant
      state rather than as a result of preeclampsia or eclampsia. According to these
      results, there is no evidence of increased production of serum autoantibodies
      against modified LDL in African women with pre-eclampsia, which may reflect
      reduced lipid peroxidation involving lipoproteins or no link at all. In addition,
      IgG and IgM anticardiolipin antibodies have no diagnostic value in preeclampsia
      and eclampsia.

PMID- 12521692
TI  - Mortality and early neonatal morbidity in vaginal and abdominal deliveries in
      breech presentation.
AB  - From January 1984 to June 1986, 268 consecutive breech presentations in two
      university hospitals were studied prospectively. Vaginal delivery was attempted
      in all cases, under expert supervision and electronic monitoring, except in the
      presence of clear-cut contraindications. For most of the examined parameters no
      statistically significant differences were found in mortality and morbidity
      between the vaginally delivered group and the caesarean section group in three
      birth weight categories. Regarding mortality a relation with the mode of delivery
      was demonstrable in two cases in the vaginal group and one case in the caesarean
      section group in the low and very low birth weight category. In the 500-1499 g
      birth weight category, underestimation of the birth weight during pregnancies led
      to iatrogenic neonatal death in two cases. Our study shows that the management of
      breech presentation can be modified in order to stop the increase in caesarean
      section rate and diminish the degree of variation in operative delivery without
      affecting the perinatal outcome.

PMID- 12521693
TI  - Can the fetal-pelvic index predict fetal-pelvic disproportion during vaginal
      breech delivery?
AB  - Fetal-pelvic index can be a sensitive and specific predictor of feto-pelvic
      disproportion. This can be of value when contemplating vaginal breech delivery.

PMID- 12521694
TI  - A psychosocial analysis of women planning birth outside hospital.
AB  - Most of the women requesting out-of-hospital delivery considered delivery a
      natural process, not an illness requiring hospital care. The women cited freedom
      of choice concerning the delivery, less anxiety in the home than in the hospital
      environment, a more personal relationship with the midwife, and, as far as
      possible, making do without medical equipment. The interviewed women were a
      selected collective regarding age, parity, socioeconomic status and obstetric
      risk profile. Nonetheless, the results suggest ways that in-hospital obstetrics
      can be adapted to meet the requirements of pregnant women. Individualized, family
      oriented obstetrics with judicious use of medical technology should be possible
      in the clinical setting.

PMID- 12521695
TI  - A clinico-epidemiological review of cervical cerclage from the Assir region of
      Saudi Arabia.
AB  - A retrospective review was conducted on patients who had cervical cerclage
      performed because of suspected cervical incompetence over a 7-year period to
      assess the outcome of pregnancy and complications resulting from the cerclage.
      Other factors that could affect the outcome and complications were also assessed.
      Out of 196 patients who had the operation, 154 patients had adequate records
      available and therefore comprised the study population. There were 139 (90%) live
      births of which 76.6% weighed more than 2000 g. The outcome was not influenced by
      the experience of the surgeon, type of cerclage or the use of prophylactic
      antibiotics. There were no complications in 138 (90%) of the cases, and no cases
      of ruptured uterus, cervical lacerations and severe infections were encountered.
      The complications were seen more in multiple-order pregnancy and when the
      operation was performed as an emergency. The future role of cervical cerclage in
      the management of cervical incompetence in our community is discussed.

PMID- 12521696
TI  - Dying undelivered.
AB  - This paper aims to stimulate discussion and awareness of this double tragedy of
      obstetric practice in the tropics. This was an 8-year retrospective review of all
      the patients who died undelivered in a tertiary health care institution serving a
      population of over a million people. The incidence of dying undelivered was
      141/100 000 deliveries and this was highest in the extremes of age and parity.
      Patients who died undelivered contributed 28.30% of all the maternal deaths in
      the hospital during the period of study. The maternal mortality rate in the
      unbooked patients who died undelivered was three times that for the booked.
      Severe hypertension and ruptured uterus were the greatest association in patients
      who died undelivered. More than 46% of the fetuses were alive for more than 6
      hours from the time of admission to the time of demise of their mothers. Most of
      the deaths, both maternal and perinatal, were avoidable. Dying undelivered is a
      significant aspect of maternal deaths in the tropics. The right of the helpless,
      unborn fetus of a moribund mother should be protected as much as possible. More
      reports are needed urgently to create awareness about the place of post mortem
      caesarean section.

PMID- 12521697
TI  - First-trimester pregnancy scanning as a screening tool for high-risk and abnormal
      pregnancies in a district general hospital setting.
AB  - This study set out to evaluate the feasibility and acceptability of routine early
      ultrasound (12-14 weeks) within a district general hospital (DGH) for identifying
      high-risk and abnormal pregnancies. This was a pilot study for screening by
      ultrasound examination all women who presented to their community midwife before
      12 weeks' gestation. The study involved 991 women who presented clinically
      pregnant before 12 weeks' gestation between May 1998 and May 1999. Women were
      offered routinely two ultrasound examinations during their pregnancy, the first
      at 12-14 weeks' gestation and the second at 20-21 weeks' gestation. The main
      outcome measures were: range and number of abnormal/high-risk pregnancies
      identified during an ultrasound scan at 12-14 weeks' gestation; range and number
      of abnormalities diagnosed during scans at later gestations; outcomes of the
      pregnancies; questionnaires assessing how the women viewed early pregnancy
      ultrasound as a method of screening. Nine hundred and eighty-four (99%) women
      accepted the offer of an early ultrasound scan at 12-14 weeks' gestation; of
      these 840(85%) women accepted screening for trisomy 21 (T21) by fetal nuchal
      translucency thickness (NT) and maternal age (fetal medicine foundation risk
      assessment programme) and this was completed successfully in 797(80%) of cases.
      Twenty-four women (2%) had a failed pregnancy and where necessary an ERPC was
      performed following a planned admission. Thirty pregnancies (3%) were diagnosed
      as abnormal or having high risk of abnormality at the early scan. A major
      abnormality was confirmed before the expected anomaly scan at 20 weeks in five
      (17%) pregnancies; all of these patients opted for an elective termination.
      Twenty-six (3%) pregnancies had a diagnosis of abnormality at their anomaly scan.
      Of these, three pregnancies were diagnosed as major abnormalities with two
      resulting in termination of the affected pregnancy before 24 weeks' gestation.
      Eight hundred and thirty-seven women (85%) completed questionnaires, 833 women
      (84.5%) were satisfied with the counselling they received before the ultrasound
      scan and 827 women (84%) answered that they would accept an early pregnancy scan
      if offered during their next pregnancy. Early pregnancy ultrasound at 12-14
      weeks' gestation can be used as an effective method of identifying and screening
      for major abnormalities of pregnancy within a DGH setting, but it is appropriate
      to use this in conjunction with an anomaly scan at around 20 weeks' gestation.
      Women found this method of screening acceptable.

PMID- 12521698
TI  - Sexuality among pregnant women in South West Nigeria.
AB  - The sexual activity of 500 pregnant women in Ilesa, Nigeria was investigated in a
      prospective study carried out at the antenatal clinic of the Wesley Guild
      Hospital, Ilesa between December 1999 and September 2000. While the sexual desire
      in pregnancy of most of the women (60%) remains the same as in the non-pregnant
      state, coital frequency was reduced in majority of them (64%). The reasons given
      by the respondents for reduced sexual activity include nausea and vomiting of
      early pregnancy (30%), fear of miscarriage (12%), fear of harming the fetus
      (12%), physical awkwardness (20%), lack of interest (10%), discomfort (6%), fear
      of membrane rupture (8%), fear of infection (8%) and fatigue (10%). Coital
      frequency, however, remained the same in 32% and increased in 4% of the women.
      The reasons for this include: "it helps to keep the husband around" (3%),
      maintain marital harmony (20%), satisfying (16%) and will facilitate labour in
      late pregnancy (6%). The findings from this study suggest a mixed-feeling effect
      with a tilt towards a positive attitude to sexuality in pregnancy. The health
      professional should favour the complete enjoyment of sexual activity during
      pregnancy.

PMID- 12521699
TI  - Musculo-skeletal problems associated with pregnancy in women with osteogenesis
      imperfecta.
AB  - Having seen a number of women with osteogenesis imperfecta who developed severe
      back pain during or just after pregnancy, we wished to determine the likelihood
      of this and other musculoskeletal problems in pregnancy. We interviewed by
      telephone 100 women with osteogenesis imperfecta who had, between them, 213
      pregnancies between 1957 and 1998. For each pregnancy we recorded the Sillence
      type for the osteogenesis imperfecta, the mode of delivery and the musculo
      skeletal complications. The most common problem was back pain, which was severe
      in or after 28 pregnancies (13.1%). There was no identifiable relationship to the
      type of osteogenesis imperfecta or to the mode of delivery. In many cases the
      back pain could be related to crush fractures of vertebrae. Other problems
      identified included spinal deformity, non-vertebral fractures, disc problems and
      ligament problems. We suggest that it may be appropriate to advise the avoidance
      of long periods of breast feeding in women with OI, particularly in those who
      have vertebral fractures.

PMID- 12521700
TI  - Twin pregnancy in a tertiary referral unit--analysis of trends in the 1990s.

PMID- 12521701
TI  - A wise baby knows its mother! Do babies born after ovum donation successfully
      breast-feed?

PMID- 12521702
TI  - Evaluation of ventouse failures in a district general hospital.

PMID- 12521703
TI  - Prevalence of Group B streptococcal infection colonisation in pregnant women and
      their offspring in the Middle East.

PMID- 12521704
TI  - Role of red cell selenium in recurrent pregnancy loss.
AB  - Selenium is an essential trace mineral required for normal human health and
      reproduction. In recent years selenium deficiency in humans has been implicated
      as a risk factor for recurrent pregnancy loss. So far the selenium status in
      recurrent pregnancy loss (RPL) has been evaluated only in plasma and serum
      samples showing discrepancies of selenium deficiency as a cause for RPL. The
      present pilot study from India has evaluated selenium status in red cells (as
      they are the better indicators of selenium levels) in 20 women with three or more
      unexplained recurrent pregnancy losses compared to similar number of controls.
      The mean+/-SD red cell selenium levels in the study group was found to be
      119.55+/-32.94 ng/ml (range 55-170 ng/ml), which was significantly lower compared
      to the control group with a mean+/-SD of 150.85+/-37.63 ng/ml (range 87-225
      ng/ml). The difference was statistically significant at the 1% level ( P <0.01).
      Since selenium supplementation resulted in successful pregnancy outcome in
      veterinary practice, we conclude that large randomised studies are needed to
      assess the contribution of selenium in the aetiology of RPL and the potential
      benefits of its supplementation.

PMID- 12521705
TI  - Medical termination of missed abortion.
AB  - Missed abortions are a common occurrence and represent a heavy gynaecological
      emergency workload to both medical and nursing staff. The conventional method
      using vacuum aspiration of uterus is associated with morbidity and mortality.
      Medical termination of pregnancy is accepted as a safe and effective alternative
      method. However, medical evacuation of uterus in missed abortions had not been
      fully investigated. In this study we hope to examine the efficacy of medical
      methods for terminating missed abortions. Mifepristone and misoprostol prescribed
      to 100 women with an ultrasonically confirmed missed abortion was compared with
      100 women who had surgical evacuation under general anaesthesia for their missed
      abortion. The disparity in complications between medical and surgical groups was
      not significantly different (Student's t-test, P=0.5). This study showed medical
      evacuation of missed abortion to be an effective, safe and cost-effective,
      alternative to surgical evacuation of the uterus and is particularly suited to
      women not wanting hospital admission or a surgical procedure under general
      anaesthesia. It represents an option of management that can be less intrusive and
      gives the woman some control but is both safe and effective.

PMID- 12521706
TI  - Study of the levator ani muscle in the multipara: role of levator dysfunction in
      defecation disorders.
AB  - The levator ani muscle (LAM) shares in the mechanism of defecation and urination
      as well as in visceral support. Levator dysfunction occurs in conditions of
      chronic straining or increased intra-abdominal pressure. Studies have shown that
      the gravid uterus, by virtue of its weight and associated increased
      intraabdominal pressure, might disturb the levator function. It is postulated
      that this effect is augmented with repeated pregnancies. The current study
      investigated the functional activity of the LAM in 50 multipara, 30 primipara and
      20 nullipara (controls). The 50 multipara (age 46.4 years, 4-7 deliveries) were
      divided into group A (28 women with normal deliveries) and group B (22 women with
      a prolonged 2nd stage of labour). Of the 30 primipara (age 44.2 years) 18 had
      normal delivery (group A) and 12 prolonged 2nd stage of labour (group B). The
      mean age of the nullipara was 45.3+/-7.6. The LAM activity at rest and on
      contraction was recorded. The rectal and anal canal pressure response to LAM
      stimulation was also registered. In group A of the multipara, the LAM EMG
      activity at rest was similar to (P>0.05), and on contraction lower (P<0.05) than
      the LAM EMG of the controls (nullipara). Group B exhibited a lower activity at
      rest and on contraction (P<0.01, both). Primipara group A had a resting and
      contractile EMG activity similar to the controls, while group B showed diminished
      activity in both conditions (P<0.05, both) which was significantly higher
      (P<0.05, P<0.01, respectively) than that of group B multipara. The rectal
      pressure in the multipara and primipara did not differ from the nullipara
      (P>0.05, both). In groups A and B of multiparous women, the anal canal pressure
      at rest was significantly lower and on LAM contraction significantly higher than
      that of nullipara. Group A of the primipara showed no significant difference
      against the controls, while group B exhibited a decline at rest (P<0.05) and no
      difference on LAM contraction (P>0.05). In conclusion, levator dysfunction might
      occur in the parous women. It was more common in the multipara than the primipara
      and in particular those with a history of a prolonged 2nd stage of labour.
      Levator dysfunction may lead to constipation and faecal or urinary incontinence
      as a result of pudendal neuropathy and the development of pudendal canal
      syndrome.

PMID- 12521707
TI  - Follow-up after negative large loop excision of the transformation zone (LLETZ)
      of the cervix.
AB  - We performed a retrospective analysis of 204 patients who underwent large loop
      excision of the transformation zone (LLETZ) to determine whether women who have a
      negative LLETZ (no cervical intra-epithelial neoplasia (CIN) present) are at a
      lower risk of developing further abnormal cytology or CIN than women whose LLETZ
      is positive (CIN present). Overall 69 of the LLETZ samples were negative (34%)
      and 135 were positive (66%). The mean duration of negative cytology during follow
      up was 25.4 months (negative LLETZ) and 21.2 months (positive LLETZ) (P=0.03). In
      the negative LLETZ group, cytology did not miss any cases of persistent CIN at
      the 6-month follow-up visit and 39 repeat punch biopsies were all negative. There
      were 3/69 cases (4.3%) in the negative LLETZ group and 13/135 (9.6%) in the
      positive LLETZ group of persistent disease (CIN diagnosed at or as a result of
      the 6-month follow-up). Following a negative 6-month review, one woman developed
      an abnormal smear in the negative LLETZ group (1/66=1.5%) compared with 10 women
      (10/122=8.1%) in the positive LLETZ group. Recurrent CIN (CIN subsequently
      diagnosed following a negative 6-month review) was seen in 0/69 cases (0%) in the
      negative LLETZ group and 4/135 (3.2%) in the positive LLETZ group. We conclude
      that women who undergo a negative LLETZ may represent a low-risk group for
      developing further cytological and histological abnormalities.

PMID- 12521708
TI  - Management of ectopic pregnancy in a Scottish teaching hospital: implications for
      training.
AB  - An audit was undertaken to assess the management of 50 consecutive women with an
      ectopic pregnancy at a teaching hospital in Scotland. The ectopic pregnancy was
      removed laparoscopically in 62% and of these women 80% were discharged home on
      the first postoperative day. In a minority of patients, elements of substandard
      care were identified including failure to operate when the ectopic pregnancy had
      been visualised on ultrasound or in the presence of static hCG levels in patients
      with an empty uterus and adnexal pain. Fewer than 50% of consultants and no
      junior registrar reported competency in the laparoscopic management of these
      patients. We suggest that the management of ectopic pregnancy could be improved
      by following published algorithms with high diagnostic accuracy. In addition,
      either skilled endoscopic teams should be developed to take on the responsibility
      of the management of these patients or universal consultant competency in
      laparascopic surgery is required if we are to offer laparoscopy to all women with
      ectopic pregnancy.

PMID- 12521709
TI  - Microwave endometrial ablation: patients' experiences in the first 3 months
      following treatment.
AB  - The aim of this study was to investigate patients' experiences in the first 3
      months following microwave endometrial ablation (MEA) for menorrhagia as well as
      the suitability of local anaesthesia (LA) versus general anaesthesia (GA) for
      these procedures. We carried out a cross-sectional questionnaire survey of 173
      patients at 3 months after treatment with MEA. All were treated between September
      1997 and December 1999. The setting was a small free-standing hospital day unit
      equipped with a minor operating theatre. Interventions were pretreatment with
      danazol or goserelin, followed by endometrial ablation with microwaves under GA
      or LA. Of the 173 patients, 98 (57%) were treated under GA, and 75(43%) under LA.
      The return of questionnaires was high in both groups (90% for GA and 84% for LA)
      and all procedures were completed with the planned anaesthetic. Commonly reported
      symptoms were immediate postoperative pain (61%), abdominal pain in the following
      weeks (75%), vaginal discharge (87%), vaginal bleeding (74%) and vaginal dryness.
      Reported symptoms were usually mild and not requiring medical intervention, e.g.
      in 124 patients (71%), postoperative pain was either absent or mild with no
      analgesics required. Only 4% had severe pain requiring a single dose of opiate
      analgesia. The results were similar in both groups. Sixty-nine per cent (104
      patients) had no pain 1 week after treatment. This increased to over 90% by the
      end of the third week. Results were similar in those treated under LA (83% and
      96%, respectively). There was early return to normal daily activity (70% by 1
      week and 95% by 3 weeks). Reported symptoms were usually mild and not severe
      enough to warrant consultation of their doctor or the hospital. There were no
      blood transfusions or hysterectomy within the first 3 months of treatment. We
      conclude that MEA is well tolerated by patients. Reported side effects are
      usually minor. LA is comparable to GA and seems to have potential benefits.

PMID- 12521710
TI  - Balloon ablation: is this an outpatient procedure?
AB  - Menorrhagia is associated with considerable health consequences. First-line
      therapy is medical, but when this proves unsuccessful a surgical procedure is
      often undertaken. It is estimated that as many as one in five women will have a
      hysterectomy before the age of 60 years. While a curative procedure this is a
      major operation with both morbidity and mortality associated with it. More
      conservative procedures have therefore been sought. Balloon therapy was developed
      in 1994 and it was introduced to Royal Bolton Hospital in 1998. Initially offered
      under general anaesthesia, an overall a success rate of 91% was achieved in this
      study, with amenorrhea in 18% of cases. Dysmenorrhea was improved in 60% of
      patients. Twenty-eight patients received outpatient therapy, under a paracervical
      block. All patients were given voltarol pretreatment. Subjectively the procedure
      was well tolerated by most, and objectively 89% of patients rated the procedure
      as acceptable. Sixty-one per cent of patients would be happy to undertake the
      procedure again under local anaesthesia. Findings from this study would indicate
      that balloon ablation does provide an effective, less invasive, alternative
      treatment for menorrhagia. Despite limited numbers, it would also seem
      appropriate, in selected patients, to offer this therapy as an outpatient
      procedure.

PMID- 12521711
TI  - Genital lichen sclerosus associated with incontinence.

PMID- 12521712
TI  - The knowledge, attitude and practice of child adoption among infertile Nigerian
      women.
AB  - To determine the knowledge, attitude and practice of child adoption among
      infertile Nigerian women we undertook a questionnaire survey of 279 consecutive
      infertile women seen in three tertiary care centres in South Eastern Nigeria
      within a 9-month period. The data were analysed by means of simple percentages
      and descriptive and inferential statistics, using t-tests, chi-square tests and
      regression equations at the 95% confidence level. Two hundred and sixty-four
      questionnaires were analysed. Although 228 (86.4%) of the respondents were aware
      of child adoption, only 72 (27.3%) knew its correct meaning. Fifty-seven (21.6%)
      women knew how to adopt a baby while the rest did not; 183 (69.3%) respondents
      expressed their unwillingness to adopt a baby while the remaining 81 (30.7%) were
      willing. Twelve (14.8%) of these 81 respondents (or 4.5% of all respondents) had
      either adopted or made an effort to adopt a child at the time of the study. The
      major reasons given by the 183 respondents unwilling to adopt a child were:
      adoption not a solution to their infertility (84 respondents); adoption
      psychologically unacceptable (78 respondents); fear of unknown parental
      background (75 respondents) and abnormal behaviour in the child (75 respondents).
      Univariate analysis showed six factors significantly associated with a favourable
      attitude to child adoption: a correct knowledge of the meaning of adoption
      (P=0.00007), duration of infertility >5 years (P=0.0002), previous orthodox
      specialist treatment (P=0.0002), tubal infertility (P=0.002), no living child
      (P=0.02) and maternal age >35 years (P=0.03). In a multiple logistic regression
      involving these six factors, with attitude to adoption as the dependent variable,
      two factors were associated significantly with a favourable attitude to adoption:
      correct knowledge of the meaning of adoption (OR=1.9, P=0.04) and previous
      orthodox specialist treatment (OR=2.9, P=0.05). Although the majority of
      infertile Nigerian women have heard of child adoption, only a minority knew its
      real meaning, its legality and the process it entails. Approximately one-third of
      them were disposed favourably to adoption as a treatment option for their
      infertility. The Nigerian experience was compared and contrasted with the
      experiences of other countries. Factors associated with a favourable attitude to
      adoption were presented and discussed. In the presence of such factors,
      especially when the probability of cure of infertility is small, child adoption
      as a treatment option should be offered early so that willing couples can
      initiate the processes.

PMID- 12521713
TI  - Cordocentesis to predict fetal outcome after administration of radio-active
      iodine for Graves' disease.

PMID- 12521714
TI  - Successful treatment of pseudomyxoma peritonei with intraperitoneal 10 per cent
      dextrose, sizofiran and cisplatin.

PMID- 12521717
TI  - Epithelial ovarian cancer and infertility treatment.

PMID- 12521718
TI  - The light thrown on the causes of fatty liver of pregnancy by the sex ratio of
      associated offspring.

PMID- 12521719
TI  - How do fathers feel after accompanying their partners in labour and delivery?
AB  - This study aims to investigate fathers' experiences of labour and delivery and
      compare their emotions from different types of delivery. One hundred and twenty
      one couples were given questionnaires following the delivery of their babies
      after labour before discharge from the hospital where they were required to rate
      their feelings on a visual analogue scale. Generally, fathers were keen to
      accompany their partners during labour, with 81% giving a score of 9 or above.
      Most of them found the experience rewarding and enjoyable, but they found
      operative delivery more traumatic compared to normal vaginal delivery (P=0.003
      for caesarean section and P=0.032 for instrumental delivery) and expressed
      increased anxiety at caesarean sections in labour (P=0.005). Women underestimated
      their partners' positive experiences during labour and found them more helpful
      than their partners had felt. Both partners felt their relationships with each
      other had improved following their shared experiences irrespective of mode of
      delivery.

PMID- 12521720
TI  - Maternal and fetal risks associated with prolonged latent phase of labour.
AB  - A pregnancy cohort study was undertaken to assess the fetal, maternal and
      obstetric risks associated with the prolonged latent phase of labour. One hundred
      and fifty cases (latent phase >8 hours) were compared with 100 controls (latent
      phase <8 hours). Data were collected from hospital records. There were more
      nulliparas in the case group (73% vs. 39%; P<0.0001). Cases required oxytocin
      augmentation (62% vs. 17%; P<0.0001) and caesarean section (29% vs. 6%; P<0.0001)
      more frequently than controls. Thick meconium staining of the liquor was more
      frequent in cases (15% vs. 5%; P<0.05), as were 5-minute Apgar scores less than 7
      (17% vs. 3%; P<0.001) and admission to the neonatal unit (22% vs. 1%; P<0.0001).
      Prolonged latent phase is associated with increased risks for obstetric
      intervention and poor fetal outcome. The optimal management of prolonged latent
      phase is still unknown and requires further study by means of randomised
      controlled trials.

PMID- 12521721
TI  - Severe burn injury in pregnancy in Northern Nigeria.
AB  - A total of 21 cases of severe burns in pregnancy managed at the University of
      Maiduguri Teaching Hospital, Maiduguri, over a 10-year period, spanning January
      1991-December 2000 inclusively were reviewed. The pregnancy loss was 92.9%, with
      the pregnancies spontaneously terminated within 10 days of sustaining the injury.
      Maternal mortality was 47.6% with sepsis as the most common cause of death. It is
      advocated that viable pregnancies should be terminated as soon as the mother is
      resuscitated following severe burn injury. Prophylactic systemic antibiotics
      should be given to minimise the development of sepsis. Patients are best managed
      in the obstetrics ward during the first 2 weeks of injury. A multidisciplinary
      approach is encouraged in managing cases of severe burns in pregnancy.

PMID- 12521722
TI  - Fetal lacerations at caesarean section.
AB  - Fetal lacerations occurred in 1.5% of caesarean sections carried out in our
      institution. The incidence was independent of type of caesarean section, fetal
      presentation, cervical dilatation, presence of intact membranes or operator
      grade. We advocate that this complication should be included in the preoperative
      counselling of all patients undergoing caesarean sections.

PMID- 12521723
TI  - Impact of asymptomatic maternal malaria parasitaemia at parturition on perinatal
      outcome.
AB  - A cross-sectional study involving 564 parturients who delivered singleton babies
      and 214 matched non-pregnant controls was carried out to determine the prevalence
      and impact of asymptomatic maternal malaria parasitaemia at parturition on the
      perinatal outcome. One hundred and forty (24.8%) parturients and 50 (23.4%) non
      pregnant women were found to have asymptomatic malaria parasitaemia,
      respectively, while the congenital malaria rate in the neonates of the
      parasitaemic parturients was 0.7%. The incidence of malaria parasitaemia was
      higher in the para 2 and over (29.33%) as compare to the para 1 (21.43%) and
      primigravid (18.42%). There was no significant difference between the mean birth
      weight of infants delivered by parasitaemic parturients (2.93+/-0.61 kg) and
      aparasitaemic parturients (3.07+/-0.32 kg) (P=0.501). There was also no
      significant difference when comparing the mean placental weight of the
      parasitaemic mothers (0.60+/-0.15 kg) with that of the aparasitaemic mothers
      (0.62+/-0.20 kg) (P=0.329). Only in the para 2 and over was the mean placental
      weight of the parasitaemic mothers significantly lower than that of the
      aparasitaemia mothers (0.46+/-0.16 kg; 0.66+/-0.23 kg P=0.035). The mean packed
      cell volume of the parasitaemics parturients (30.89+/-1.87) was significantly
      lower than the aparasitaemic parturients (31.98+/-2.25) (P<0.001). Significant
      difference was not achieved between the parasitaemics and aparasitaemics
      inrespect of apgar score at 1 minute, or at 5 minutes, premature births (16.43%;
      15.33%; P>0.05), stillbirth rate (3.57%; 2.59, P>0.05), mean placental index
      (0.204, 0.202, P>0.50) and mode of delivery. The findings in this study show that
      even though malaria parasitaemia is prevalent in our locality, the effects on
      maternal and fetal wellbeing are comparable with the aparasitaemics.

PMID- 12521724
TI  - Fetoplacental leptin levels and their relation to birth weight and insulin in
      gestational diabetic pregnant women.
AB  - To investigate the fetoplacental leptin circulation in gestational diabetes, we
      compared cord leptin and insulin levels in 17 healthy pregnant women and 17 women
      with gestational-onset diabetes. Leptin levels in the umbilical arteries (mean+/
      SD 1.80+/-0.76 ng/ml) were significantly (P<0.006) lower than those in umbilical
      veins (2.67+/-0.98 ng/ml) in normal pregnancies. Similarly, leptin levels in
      umbilical veins (mean+/-4.59+/-1.60 ng/ml) were significantly (P<0.001) higher
      than those in umbilical arteries (mean+/-SD 2.08+/-0.90 ng/ml) in gestational
      diabetes. However, leptin levels in umbilical veins were significantly higher
      (P<0.002) in gestational diabetes than those in controls. Additionally, in women
      with diabetes but not in controls, the birth weight and the cord leptin
      concentrations were positively related to cord insulin levels. We conclude that
      there is a hyperleptinaemia in the fetoplacental circulation in pregnant women
      with carbohydrate intolerance and in these cases insulin and leptin may have
      antagonist roles regarding fetal development.

PMID- 12521725
TI  - Assessment of stillbirth risk and associated risk factors in a tertiary hospital.
AB  - We aimed to calculate the stillbirth rate at each gestation and also determine
      antenatal factors, which may be associated with unexplained stillbirth in a large
      UK teaching hospital. This was a retrospective study of all the stillbirths
      between January 1995 and October 1998. There were 27 170 births at > or =24
      weeks, gestation during the study period. Of these 161 were stillbirths giving a
      stillbirth rate of 5.9/1000; 149 (92.5%) were antepartum. Eighty-two (50.9%) were
      unexplained. The "risk" of unexplained stillbirth per 1000 ongoing pregnancies
      was 0.3 at 24-25 weeks, fell steadily to 0.07 at 30-31 weeks and then rose to a
      peak of 1.16 at 40-41 weeks. About half (49.2%) of the pregnancies that ended in
      unexplained stillbirths had a normal antenatal course with no associated factors.
      Associated factors in the unexplained stillbirth group were identified in 50.8%
      of cases. The most common was intrauterine growth restriction, identified in
      41.5% of cases. The "risk" of stillbirth increases at term. No significant
      antenatal associated factor, detection of which would aid prevention, could be
      identified in the majority of cases.

PMID- 12521726
TI  - Reduction in the occurrence of uterine rupture in Central India.
AB  - This study was carried out in the Department of Obstetrics and Gynaecology of the
      Mahatma Gandhi Institute of Medical Sciences, Sevagram in Central India. In the
      12 years between 1989 and 2000 a total of 16 cases of ruptured uterus were
      managed, the incidence of rupture of the pregnant uterus being 0.62 per 1000
      births. One-quarter of the cases occurred between 1983 and 1988. No teenager or
      elderly woman (over 40) or grandmultipara sustained a uterine rupture. Four women
      had a rupture of a previous scar. In five rupture had occurred in association
      with malpresentations, one was a case of hydrocephalus, two had a morbidly
      adherent placenta praevia and four had a normal presentation, with lack of
      progress in labour. Two of these 16 women had twins. One had come with a retained
      second twin with transverse lie and the other was a booked case with multiple
      problems, including a previous caesarean section, present twin pregnancy and
      placenta praevia accreta and she died. This was the only maternal death.
      Perinatal mortality was 77.77% compared to 5.88% maternal and 100% perinatal
      mortality in the cases reported previously between 83 and 88, from the same
      institution. Overall, there is some improvement in perinatal survival and one
      quarter incidence of rupture of the pregnant uterus.

PMID- 12521727
TI  - Pregnancy outcomes following treatment of cancer.
AB  - While still rare, cancer has the reputation of being life-threatening in all its
      forms. Coupled with the survival of cancer comes a growing expectation from the
      patients that their life should be relatively unaffected. Among the side effects,
      there is frequently an effect on fertility. In particular, the treatment of the
      young with anti-cancer therapy raises questions about the patient's ability to
      achieve normal reproductive function and delivery following treatment. Between
      1987 and 1998 we identified 40 women who conceived or delivered a fetus following
      treatment for cancer. They had undergone a combination of therapies including
      surgery, chemotherapy and radiotherapy. Four had elected to be sterilised after
      completion of their family. It did not appear from the data collected that the
      therapy used for treatment of some cancers has had an adverse effect on delivery
      outcomes, expected weight of the fetus or the gestation of the pregnancy.

PMID- 12521728
TI  - The presence of residual disease in the cervix of hysterectomy specimens from
      women in whom there has been a previous diagnosis of cervical carcinoma.
AB  - The frequency with which residual carcinoma was encountered in 33 simple
      hysterectomy and 52 radical hysterectomy specimens from women who had squamous
      cell carcinoma (67), adenocarcinoma (8), adenosquamous carcinoma (3) and other
      tumours (7) of the cervix was studied. Predicted pathological stage was IaI (32
      cases), IaII (10), Ib (16) and IIa tumour (1). Patients whose original procedure
      consisted of a punch biopsy were predicted to have microinvasive disease (Stage
      IaI or IaII - 10 cases) and Ib lesions (11 cases). One patient's initial
      investigation consisted of a curettage and in four patients the stage could not
      be predicted. Margins of the original specimen were assessable in 54 cases (28
      positive, 26 uninvolved). Residual tumour was identified in 32 cases and in eight
      was of higher stage than predicted. It was most likely to be identified if the
      original diagnosis was made on punch biopsy with no intervening treatment or in
      Stage IaII disease or greater. These results highlight the importance of thorough
      examination of the cervix attached to a hysterectomy specimen in patients with a
      diagnosis of invasive cervical carcinoma.

PMID- 12521729
TI  - The variation in urodynamic practice in the United Kingdom.
AB  - The object of this study was to determine the variation in urodynamic practices
      in the United Kingdom. One hundred questionnaires were sent to units known to be
      performing urodynamic investigations. It was obvious that there was a significant
      variation in practices with only 51% of units having a protocol for what tests
      should be performed, under what circumstances and how. Standardisation of
      urodynamic variables may result in a greater consistency of diagnosis, allowing
      easier comparisons of treatment regimes and outcomes.

PMID- 12521730
TI  - A politico-medical perspective of induced abortion in a semi-urban community of
      Ile-Ife, Nigeria.
AB  - This study is designed to document a semi-urban community perspective on induced
      abortion in Ile-Ife, Nigeria, with a view to estimating community awareness,
      attitudes and implications of its existence in the community and providing
      relevant sociopolitical policies and pragmatic educational guidelines for policy
      makers to solve some of its problems within the Nigerian landscape and beyond.
      This was a cross-sectional study conducted in April 2000, at Oranfe community in
      Ile-Ife, South West, Nigeria, which has an estimated population of 5250
      inhabitants. We used the survey method with the aid of a well-structured
      questionnaire. One hundred and eighty residents of the community were sampled as
      our subjects for this study. We used the cluster random sampling technique. The
      main outcome measures were the sociodemographic characteristics of the
      respondents, knowledge, attitude with perceived solutions to the problems of
      abortion and relationship of the sociodemographic factors to respondents'
      knowledge and attitude. The respondents were highly literate, as only 18 (11.04%)
      had no formal education. Eighty-five (52.79%) had good knowledge of abortion
      while 45 (27.95%) and 31 (19.25%) had fair and poor knowledge, respectively.
      Thirty-eight (24.05%) respondents felt that the solution to the problems of
      induced abortion can be obtained through its legalisation; 31 (19.62%)
      respondents believed that the solution lies in liberalising laws on abortion;
      provision of safe abortion services was suggested by 30 (18.98%) respondents. One
      hundred and seven (66.88%) felt that legalisation of abortion will increase its
      practice while 53 (31.12%) felt that such legalisation will not increase the
      practice. Similarly, 55 (34.37%) of the respondents emphasised that legalisation
      would reduce the problems of induced abortion compared with 82 (51.25%) who felt
      otherwise. One hundred and twenty (73.61%) of the respondents did not believe
      that the position of the law in Nigeria can stop the practice of induced
      abortion. Solving the problems of induced abortion in Nigeria requires pragmatic
      and non-hypocritical sex educational policies, which are widely embracing to
      sensitise people in the community through public enlightenment programmes.

PMID- 12521731
TI  - Complicated induced abortion in Sagamu, Nigeria.
AB  - A review of cases of induced abortion managed at Ogun State University Teaching
      Hospital, Sagamu from January 1988 to December 1997 is presented. One hundred and
      two cases were treated for various complaints and complications of induced
      abortion during the period of review. The mean age in years was 24.6+/-5.8. The
      groups 20-24 years, 15-19 years and 25-29 years constituted 39.2%, 23.5% and
      18.6%, respectively, of the patients. Mean parity was 1.7+/-1.8. Thirty-eight
      point two per cent, 30.4% and 17.6% were para zero, 2-4 and 1, respectively.
      Fifty-one per cent of the patients were single. Thirty-four point three per cent,
      15.7% and 2.0% of the patients have had one, two and three induced abortions
      before. Forty-five point one per cent of the patients refused to disclose where
      and who performed the abortion, while 31.4%, 10.8% and 7.8% of the abortions were
      carried out by physicians, quacks and nurses. Forty-five point one per cent of
      the patients procured the abortion at the gestational age of 13-24 weeks, while
      26.5% waited for 10 days and over after the abortions before seeking for medical
      help. Thirty-six point eight per cent and 26.3% of operators in fatal cases were
      physicians and nurses, respectively. The mean admission interval after abortion
      for fatal cases was 11.1+/-3.2 days and 4.0+/-3.5 days for other cases that
      survived and the difference was significant (t=8.0930; P<0.001). Eighty-five
      point three per cent had never used any form of contraception. Seventy-nine point
      four per cent, 61.8% and 6.9% of the patients presented with bleeding per
      vaginam, abdominal pains and fever, respectively. The most common complications
      were anaemia (56.9%), haemorrhages (46.1%), sepsis (33.3%) and maternal death
      (18.6%). The maternal mortality ratio was 18 627.5 per 100 000. The difference
      between maternal mortality ratio due to abortion and the general population
      (1578.9) was statistically significant (chi(2)=126.4281, P<0.001). Sunction
      aspiration (76.5%) and exploratory laparatomy (9.8%) were the most common
      operations performed. The findings in this series further highlight the urgent
      need to eliminate or reduce substantially the factors responsible for septic
      induced abortion.

PMID- 12521732
TI  - The aetiology and pattern of recurrent pregnancy loss.
AB  - The aims of this study were to determine the aetiological factors and the pattern
      of recurrent pregnancy loss in Kuwait. Ninety consecutive patients attending the
      special recurrent miscarriage clinic were studied prospectively. A comprehensive
      history of all previous miscarriages and pregnancies, past medical and
      gynaecological events were established. A physical examination was performed.
      Extensive investigations were performed. Pregnancies which occurred during the
      study were monitored carefully. The mean age of the patients was 30.46+/-6.04
      years. The patients were subdivided into the groups of secondary (57%) and
      primary (43%) recurrent miscarriages. Eighty-five per cent of all previous
      miscarriages occurred in the first trimester. The main aetiological factors were
      uterine anomaly 2.2%, chromosome anomaly (parental) 2.2%, PCOS, infections and
      other miscellaneous factors 21.1%, positive antiphospholipid antibodies 33.3% and
      unexplained in 35.6%. The overall live birth rate was 82% and maternal morbidity
      was low. Positive antiphospholipid antibodies are the most frequently associated
      cause of recurrent pregnancy loss in Kuwait.

PMID- 12521733
TI  - Clinical performance indicators at hysterectomy.
AB  - The short-term complications of hysterectomy in 184 women have been documented
      over 12 months against a panel of clinical performance indicators in a district
      general hospital. One hundred and fifty-nine operations (159/184, 86.4%) were
      performed by the abdominal route; 25/184 (13.6%) by the vaginal route. Clinical
      indications for hysterectomy varied from menorrhagia (75/184, 40.7%) to Stage
      III/IV endometriosis (10/184, 5.4%). Clinical performance indicators (cPI) were
      triggered in 32/184 (17.4%) cases; 19/ 184 (10.3%) triggered a single performance
      indicator, 9/184 (4.9%) triggered two performance indicators and 4/184 (2.2%)
      triggered three performance indicators. Combining the number of hysterectomies
      performed per annum (HYST 1), with the proportion of cases triggering three or
      more clinical performance indicators (HYST 2) and the rate of hysterectomy for
      histologically normal uteri weighing less than 120 g excluding genital prolapse
      (HYST 3) provides a profile of the operation for comparison with other clinical
      services.

PMID- 12521734
TI  - Factors affecting outcome of colposuspension.
AB  - A prospective follow-up study of 196 women who underwent a colposuspension
      operation for genuine stress incontinence (GSI) at the Leicester General Hospital
      between June 1991 and May 1996 (inclusive) was carried out to review the outcome
      of surgery. The outcome was based on clinical symptomatology, demonstration of
      stress incontinence in the clinic and limited postoperative urodynamic studies.
      The clinical cure rate was 91.33%. Continence rate was reduced by age above 70
      years and post-operative urinary tract infections, and not affected by previous
      colposuspension, or anterior colporrhaphy. On the other hand, previous
      colposuspension, previous pelvic floor operations and urinary tract infections
      caused a significantly higher incidence of voiding problems. Older women and
      those who have had previous bladder neck surgery need special attention in
      assessment, counselling and in choice of surgery. Reducing postoperative urinary
      tract infections might help improve the overall outcome of the operation.

PMID- 12521736
TI  - Investigating non-attendance at colposcopy clinic.
AB  - We investigated non-attendance at colposcopy clinic. This was a retrospective
      case-control study conducted to find out any specific characteristics for women
      who failed to attend their appointment at colposcopy during a 3-month period, in
      comparison to attenders. The incidence of non-attendance was 23.7%. Younger age,
      smoking, occurrence of pregnancy, previous history of termination of pregnancy,
      anxiety and follow-up appointments were more common in non-attenders.

PMID- 12521735
TI  - Occupational health hazards among health care workers in an obstetrics and
      gynaecology unit of a Nigerian teaching hospital.
AB  - The occupational health hazards among health-care workers in an obstetrics and
      gynaecology unit were investigated. A total of 78 pretested questionnaires were
      administered to the doctors, nurses and ward orderlies in the unit of Obafemi
      Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. The common
      occupational health hazards were work-related stress (83.3%), needle-stick
      injuries (75.6%), bloodstains on skin (73.1%), sleep disturbance (42.3%), skin
      reactions (37.2%) assault from patients (24.3%) and hepatitis (8.9%). Nearly half
      of the staff used diazepam, lexotan or alcohol to cope with the stress of work. A
      greater percentage of doctors compared to nurses and ward orderlies used safety
      precautions such as gloves, facemasks and aprons. All the staff employed regular
      handwashing after various procedures. However no category of staff adopted
      regularly proper disposal of needles and sharps into separate puncture-resistant
      containers. About 59% of the staff recap used needles. The implications of the
      findings were discussed and recommendations made appropriately.

PMID- 12521737
TI  - The use of fluoxetine (Prozac) in premenstrual syndrome: is the incidence of
      sexual dysfunction and anorgasmia acceptable?

PMID- 12521738
TI  - Comparison of three catheters for endometrial sampling during sonohysterography:
      results of a preliminary study.

PMID- 12521739
TI  - A life-threatening case of vitamin B(12) deficiency.

PMID- 12521740
TI  - Temporary blindness as a complication of eclampsia: observations on three cases.

PMID- 12521741
TI  - Kartagener's syndrome in pregnancy.

PMID- 12521742
TI  - Cortical blindness--a warning symptom of impending eclampsia?

PMID- 12521743
TI  - A rare but distinctive placental lesion associated with Beckwith-Wiedemann
      syndrome.

PMID- 12521744
TI  - Spontaneous pneumothorax and febrile neutropenia in pregnancy.

PMID- 12521745
TI  - Pregnancy in Nigerian women with liver cirrhosis: a report of three cases.

PMID- 12521746
TI  - Triplet heterotopic pregnancy with an intrauterine monochorionic diamniotic twin
      pregnancy and an interstitial pregnancy following in vitro fertilisation and
      transfer of two embryos.

PMID- 12521747
TI  - Uterine papillary serous carcinoma after pelvic radiation therapy for cancer of
      the cervix.
AB  - The carcinogenic effect of ionising radiation in humans has well documented in
      both atomic bomb survivors and patients exposed to therapeutic radiation.
      Patients irradiated for cancer of cervix have frequently been studied for the
      later development of secondary malignancies because treatment is relatively
      successful and many patients survive long enough to be at risk for late
      complications of radiotherapy. Most investigations have revealed an increased
      incidence of uterine sarcoma following pelvic radiation therapy for a variety of
      gynecologic disorders (Norris and Taylor, 1965; Fehr and Prem, 1974). Wagoner, in
      a review of over 1800 women treated with ionising radiation for invasive cervical
      cancer, reported a fourfold increase in risk for the later development of uterine
      sarcoma (Wagoner, 1984). In this paper we report the case of uterine papillary
      serous carcinoma 16 years after pelvic X-ray therapy for cervical cancer.

PMID- 12521748
TI  - Development of a Krukenberg tumour before detection of the primary gastric
      cancer.

PMID- 12521749
TI  - A comparison of MRI findings of uterine leiomyosarcoma before surgery and at
      recurrence.

PMID- 12521750
TI  - Intra-abdominal bleed following LLETZ.

PMID- 12521751
TI  - Bladder calculus after laparoscopic colposuspension.

PMID- 12521752
TI  - Ureteric calculus around an intrauterine contraceptive device.

PMID- 12521753
TI  - Vaginal fungal lithiasis.

PMID- 12521756
TI  - Vault haematoma prevention.

PMID- 12521754
TI  - Primary ovarian pregnancy with an intrauterine contraceptive device in situ.

PMID- 12521757
TI  - Annual meeting of the northern obstetrical and gynaecological society, perth
      royal infirmary, 18 may 2001.

PMID- 12521758
TI  - PROGRAMME.

PMID- 12521759
TI  - Session 1 - Fetal Medicine.

PMID- 12521761
TI  - Session 3 - Labour and Delivery.

PMID- 12521760
TI  - Session 2 - Maternal Medicine.

PMID- 12521764
TI  - SESSION 1 - FETAL MEDICINE.

PMID- 12521762
TI  - Session 4 - Pregnancy Outcome.

PMID- 12521765
TI  - SESSION 2 - MATERNAL MEDICINE.

PMID- 12521766
TI  - SESSION 3 - LABOUR AND DELIVERY.

PMID- 12521767
TI  - SESSION 4 - PREGNANCY OUTCOME.

PMID- 12521768
TI  - Baroreceptor sensitivity and haemodynamics in normal pregnancy.
AB  - The objective of the study was to determine baroreceptor sensitivity and
      haemodynamics during the third trimester in normal pregnancy. The study group
      consisted of 20 primigravidae. The measurements were made at 28, 30, 32, 34, 36
      and 38 weeks. The haemodynamic measurements were made by Doppler echocardiography
      and parameters calculated with standard formulae. Power spectral analysis was
      used to estimate the baroreceptor sensitivity in mid-frequency (MF) and high
      frequency (HF) bands in msec/mmHg. Statistical tests performed were paired t-test
      and correlation coefficient. The mean baroreceptor sensitivity (BRS) in the mid
      frequency band at 28, 30, 32, 34, 36 and 38 weeks were 5.19; 5.03; 5.52; 6.00;
      6.77 and 7.82 msec/mmHg. The respective values for the high-frequency band were
      7.52; 5.71; 7.99; 8.15; 8.53 and 10.87 msec/mmHg. The BRS in mid-high-frequency
      and high-frequency bands, mean arterial pressure and peripheral vascular
      resistance at 38 weeks of pregnancy were significantly higher than at 28 weeks,
      but the cardiac output was lower. A significant positive correlation of BRS with
      peripheral vascular resistance was observed. There was a significant negative
      correlation with cardiac output. The beneficial effects of increase BRS may lead
      to haemodynamic stability and stronger autonomic control of circulation. This may
      assist in maintaining a stable normal maternal blood pressure and a satisfactory
      placental perfusion during pregnancy. The absence of changes in BRS may be
      associated with pregnancy-induced hypertension and intrauterine growth
      restriction.

PMID- 12521769
TI  - Systemic inflammatory indices in pre-eclampsia and eclampsia.
AB  - The objective of this study was to test the hypothesis that TNF-alpha, TNFp55
      receptor and sICAM-1 are markers of immune activation, protective response to
      concentrations of TNF-alpha and endothelial cell activation, respectively, in pre
      eclampsia. In addition, MPO and sL-selectin were selected as blood discriminators
      of neutrophil activation. This was a cross-sectional study comparing 21 non
      pregnant controls, 29 normal pregnant controls, 21 pre-eclamptic and six
      eclamptic women. Blood concentrations of TNF-alpha, sTNFp55 receptor, sICAM-1, sL
      selectin, myeloperoxidase, leucocyte count, neutrophil count, C-reactive protein
      and gamma-glutamyl transferase were estimated. The neutrophil count was
      significantly decreased in pre-eclampsia compared with normal pregnancy (9.12+/
      0.95 vs. 12.52+/-0.80 x 10(9)/l, P<0.01). Serum concentrations of sL-selectin
      were significantly higher in non-pregnant controls compared with pregnant
      controls (P<0.0001), pre-eclampsia (P<0.0001) and eclampsia (P<0.0001). Serum
      concentrations of TNF-alpha, sTNFp55 receptor, sICAM-1, sL-selectin and MPO were
      not significantly different in women with pre-eclampsia compared with normal
      pregnancy. Serum concentrations of TNF-alpha, sTNFp55, sICAM-1, sL-selectin and
      MPO did not discriminate between normal and pre-eclamptic pregnancies. The high
      neutrophil count in normal and eclamptic pregnancies and the lack of shedded L
      selectin suggests that neutrophil exudation to inflammatory sites was increased
      in women with an accompanying inflammatory response.

PMID- 12521770
TI  - Emergency obstetric admissions: late referrals, misdiagnoses and consequences.
AB  - This is a prospective study that examined the nature of emergency obstetric
      admissions in a Nigerian university hospital in association with such factors as
      late referrals and misdiagnoses and their contribution to maternal and perinatal
      morbidity/mortality. The study comprised 144 consecutive emergency obstetric
      admissions to the hospital over a 6.5-month period. An incidence of 13.6%
      emergency admissions was recorded. Despite the proximity of the hospital to the
      parturients, most of them laboured in substandard facilities within the
      community. Referrals to the university hospital were made only after prolonged
      delay and onset of complications. Obstetric haemorrhage (24.6%) was the most
      common cause for referral followed by labour disorders (19%) and hypertensive
      disorders (8.4%). Thirteen maternal deaths occurred, giving a maternal mortality
      ratio of 6.2%, while perinatal mortality rate was 461 per 1000 births. Twelve of
      the maternal deaths were in women living within 5 km of the hospital. There was a
      caesarean section rate of 50.9%, a 4.8% incidence of diagnostic laparotomy, a 9%
      incidence of emergency hysterectomy and 44% of emergency blood transfusions.
      Misdiagnoses of clinical conditions were made by the referring centres in 68% of
      cases, which contributed to the high maternal morbidity and mortality. Patient
      attitude was the main cause of non-use of teaching hospital facilities (fear of
      operation in 32% of cases, dissuasive advice from friends in 27.4% and negative
      staff attitude in 7%). A need for and type of programme that will promote
      increased utilisation of modern maternal health services in the community are
      discussed.

PMID- 12521771
TI  - A matched controlled study of Kielland's forceps for transverse arrest of the
      fetal vertex.
AB  - This study attempted to determine whether delivery with Kielland's forceps for
      deep transverse arrest is less favourable than other instruments. One hundred and
      forty-six women who underwent rotation and delivery with Kielland's forceps
      between 1994 and 1997 were matched by parity and birth weight to one of two
      control groups: delivery by non-rotational forceps or the vacuum extractor. No
      significant differences were found in maternal or neonatal outcome (vaginal
      lacerations, 3rd- or 4th-degree perineal tears, postpartum haemorrhage, fever,
      blood transfusion, duration of hospitalisation, Apgar score, asphyxia, scalp
      trauma, admission to the intensive care unit or neonatal hospitalisation). The
      incidence of heart rate abnormalities prior to instrumental delivery was similar.
      The 'failure to deliver' rate (8.9% after Kielland's forceps) was not different
      to the 7.5% and 6.8% found in each control group. These data indicate that the
      outcome after Kielland's forceps delivery is similar to other instrumental
      deliveries if performed by experienced obstetricians.

PMID- 12521772
TI  - A prospective audit of external cephalic version at term: are ultrasound
      parameters predictive of outcome?
AB  - This prospective study was designed to audit our provision of external cephalic
      version (ECV) but also to assess the relative importance of various ultrasound
      markers as indicators of a successful outcome. Data were collected between
      November 1998 and November 1999. There were 102 breech presentations at term and
      47 women had an external cephalic version. We had an overall success rate of 55%
      with no adverse outcomes. Parity, a non-extended breech presentation and
      posterior placenta were all independently associated with a higher success rate.
      As only 49% of women with an uncomplicated breech presentation at term agreed to
      have an ECV the audit has prompted us to assess how we might improve the uptake
      of our service. Given that fetal position and placental site seem to influence
      outcome, we would suggest that a basic ultrasound scan should form part of the
      procedure. The audit has confirmed the value of ECV in reducing the incidence of
      breech presentation at term. With the increasing caesarean section rate for this
      obstetric problem it is important that all units in the United Kingdom are able
      to provide this service.

PMID- 12521773
TI  - Maternal and neonatal seroprevalence of hepatitis B surface antigen (HBsAg) in
      Benin City, Nigeria.
AB  - The seroprevalence of maternal and neonatal hepatitis B surface antigen (HBsAg)
      was determined prospectively through unlinked anonymous testing of volunteers at
      delivery at the University of Benin Teaching Hospital, Benin City, Nigeria. Six
      hundred and forty (320 mother-cord blood pairs) samples were assayed for HBsAg
      using hepatitis B latex test kit (Biotech Laboratory Ltd, UK). Repeatedly
      reactive samples were confirmed by the use of ELISA kit (Wellcome Laboratory,
      UK). None of these women had had a blood transfusion or hepatitis B vaccination
      in the past, and none was an intravenous drug abuser. The maternal seroprevalence
      was 2.19%. This means one of every 45 pregnant women was a carrier of the
      antigen. The neonatal seroprevalence and the vertical transmission rate were
      0.96% and 42.86%, respectively. The endemicity of this occasionally fatal disease
      is thus being propagated. We advocate universal free screening and immunisation
      of our pregnant women and their infants as part of the antenatal and childhood
      immunization programmes. Healthcare providers should be vaccinated routinely.

PMID- 12521774
TI  - Lymphocyte subpopulation frequency and presence of anti-cardiolipin and anti
      nuclear antibodies in peripheral blood of Kuwaiti women experiencing recurrent
      pregnancy loss.
AB  - Recurrent pregnancy loss (RPL) is often associated with elevated levels of serum
      antiphospholipid antibodies, which contribute to the pathology of the disorder by
      promoting formation of thromboses, leading to placental infarction and fetal
      loss. Patients with recurrent pregnancy loss also exhibit pathological
      alterations in composition and activity of peripheral blood lymphocytes, which
      may be indicative of an autoimmune processes. This investigation examines the
      correlation between levels of anticardiolipin antibody (AC) and specific subsets
      of the lymphocyte repertoire in RPL patients, with the objective of further
      characterising the immunological basis for RPL. Non-pregnant Kuwaiti women with a
      history of RPL were subdivided into two cohorts based on presence or absence of
      elevated plasma antibodies to cardiolipin. Whole blood from these individuals was
      analysed by flow cytometry for selected lymphocyte subsets and compared with a
      non-RPL control population. When compared with controls and low AC titre
      subjects, women with a high AC titre exhibited significantly elevated percentages
      of pathogenic CD5+ B cells; two categories of activated T cells including
      CD4+CD25+ and CD8+CD25; NK cells and CD3+NK cells; naive (CD4+CD45RA+) cells; and
      transitional (CD45RO+CD45RA+) cells. In conclusion, women with elevated levels of
      AC antibodies possess substantially higher levels of activated T cells and
      pathogenic B cells, suggesting a fundamental predisposition to immune-mediated
      rejection of the fetus by these patients. Further characterisation of this
      phenomenon may allow development of novel intervention methods for management of
      RPL.

PMID- 12521775
TI  - Risk factors for gestational impaired glucose tolerance in the Maltese
      population: a cross-sectional study.
AB  - Screening criteria for impaired carbohydrate metabolism problems during pregnancy
      include the use of specified risk factors, which are generally considered to be
      inadequate. The value of these risk factors in a population characterised by a
      high prevalence of abnormal carbohydrate metabolism is investigated. The study
      identified biological characteristics such as a maternal age >35 years, previous
      early pregnancy loss, a maternal family history of DM/IGT, pre-prandial
      glucosuria and an operative delivery with resuscitation as significant risk
      factors for the development of G-IGT. There appeared to be no statistical
      association with a history of multiparity, previous perinatal loss, congenital
      anomalies or macrosomia and a parental and grandparent family history of DM/IGT.
      There appeared to be a statistical difference in fasting blood glucose values,
      but no difference in glycosated haemoglobin. The risk factors for the development
      of G-IGT are shown to have a high specificity and negative predictive value, but
      overall moderate to low sensitivity and positive predictive values when used in
      isolation. The prevalence of the various identified risk factors was very high, a
      feature which would require at least a third of the population to be screened
      with an oral glucose tolerance test. These features suggest that the historical
      and clinical risk criteria are not ideal screening tools to identify G-IGT and a
      routine early third-trimester oral glucose tolerance test remains the ideal
      screening tool to identify these cases.

PMID- 12521776
TI  - Congenital malformations in newborns in a teaching hospital in eastern Saudi
      Arabia.
AB  - A review of 14762 singleton live-born babies during a period of 6 years at the
      King Fahad Hospital, Al-Khobar, Saudi Arabia is made with a view to study the
      clinical pattern of easily identifiable congenital malformations among neonates.
      The incidence of congenital malformations in the study was 17.0/1000 live births.
      Major abnormalities were present in 74.4% and minor ones in 25.6% of cases. The
      anatomical organs most commonly affected were the central nervous system (CNS),
      musculoskeletal and renal defects followed by gastrointestinal and chromosomal
      defects. CNS anomalies accounted for 48.8% of the total defects, hydrocephaly,
      anencephaly and meningocele being the predominant lesions. The incidence of
      malformed babies in diabetic mothers was 7.8%. Multiple anomalies were present in
      16.7% infants. Of the total 251 malformed infants, 38 died within the first week
      of life with a mortality rate of 15.1%, compared with the overall perinatal
      mortality rate of 12.2/1000 live births in the hospital during the period of
      study.

PMID- 12521777
TI  - Fumonisin B1: an aetiological role in pre-eclampsia.

PMID- 12521778
TI  - First UK experience of Mityvac vacuum delivery system.

PMID- 12521779
TI  - Audit: women's perception of transvaginal sonography in an early pregnancy
      assessment unit.

PMID- 12521780
TI  - A prospective regional audit of surgical management of endometrial cancer in the
      South and West of England.
AB  - The results of a prospective audit of surgical management of endometrial cancer
      in the South and West of England is presented. A minimum data set was defined and
      information collected prospectively. There was limited tertiary referral to a
      gynaecological oncologist. The role of centralisation of endometrial cancer care
      has been questioned, as surgery has traditionally been simple in patients
      perceived to be at increased risk of more radical surgery. However, this audit
      demonstrates that standards of even this simple care within the region are often
      inadequate, with only one-third of patients having basic staging procedures
      performed fully. This has important implications for patients management, future
      interpretation of outcome data and clinical governance in endometrial cancer
      care.

PMID- 12521781
TI  - Response to treatment in dysaesthetic vulvodynia.
AB  - Thirty-three women (mean age 45 years) attending a vulval pain clinic based in a
      department of genitourinary medicine were followed-up for a minimum of 6 months.
      All women had dysaesthetic vulvodynia and 11 (33%) also had features compatible
      with vulval vestibulitis. Thirty-two patients were treated with a tricyclic
      antidepressant drug and a complete response was recorded in 47%. Only four
      patients obtained less than 50% improvement in their symptoms. Treatment with
      tricyclic drugs was part of a package of interventions including intensive
      support and the opportunity to take up counselling. Under these circumstances, it
      is difficult to attribute the success of treatment to the effect of the
      medication alone and there is a need for well-designed randomised controlled
      trials to evaluate this and other therapeutic approaches.

PMID- 12521782
TI  - Clinical effectiveness of hysteroscopy in abnormal uterine bleeding.
AB  - The introduction of intrauterine endoscopy has allowed clinicians to evaluate an
      area of the body that was previously accessible only by the procedure of blind
      dilation and curettage (D&C). Many studies have shown hysteroscopy to be superior
      to D&C, yet its use has yet to be appreciated adequately. The use of hysteroscopy
      has been most common in the evaluation of abnormal uterine bleeding. This study
      showed that the most common indication for hysteroscopy was abnormal uterine
      bleeding (98%). Hysteroscopy was performed successfully in 91% of cases and a
      complete view of the uterine cavity was obtained. Intrauterine pathology was
      diagnosed in 60%, the highest incidence being found in those between 40 and 60
      years old (80%). The presence of endometrial polyps was the most common
      abnormality (27.3%; n=105), and increased with age to 20% in women over 60 years.
      Conversely the incidence of fibroids decreased with age; only 5% in women older
      than 60 years. Endometrial biopsy was performed in all patients and produced
      adequate tissue for histological examination in 50%. Endometrial hyperplasia and
      carcinoma was detected in 9.9%. Sixty-three women underwent a minor hysteroscopic
      procedure.

PMID- 12521783
TI  - A randomised clinical trial of loop electrosurgical excision procedure (LEEP)
      versus cryotherapy in the treatment of cervical intraepithelial neoplasia.
AB  - The objective of the treatment of cervical intraepithelial neoplasia (CIN) is the
      prevention of invasive carcinoma of the cervix, which still remains the most
      common cancer in Zimbabwean women, as in most other low-resource countries where
      screening facilities are grossly inadequate. We conducted a randomised
      prospective study to compare CIN treatment outcome after cryotherapy and loop
      electrosurgical excision procedure (LEEP) in 400 women with histologically
      confirmed high grade squamous intra-epithelial lesions (HGSIL). Treatment outcome
      measures were immediate complications, persistent disease and recurrent disease
      evaluated at follow-up visits. Eighty-two per cent of the women (159 cryotherapy,
      168 LEEP) completed their 6-month and 12-month follow-up visits. LEEP had a
      significantly higher overall cure rate of 96.4% (absence of persistent or
      recurrent disease) compared to 88.3% cryotherapy (P=0.026). Although cryotherapy
      was not superior to LEEP, its cure rate (88.3%) is acceptable and therefore
      provides a viable treatment option for low resource countries such as Zimbabwe
      where the majority of women at risk for cervical cancer reside in rural areas.

PMID- 12521785
TI  - Simplified suturing technique for sacrospinous vaginal fixation.

PMID- 12521784
TI  - The influence of reproductive and marital factors on cervical dyskaryosis.
AB  - Five hundred sexually active women attending various clinics in the Department of
      Obstetrics and Gynaecology of the University of Maiduguri Teaching Hospital had
      questionnaires on their reproductive and marital characteristics randomly
      administered. Their 'Pap' smears were then taken for cytological examination. The
      aim was to determine the influence of marital and reproductive factors on the
      occurrence of cervical dyskaryosis and how these may be used to develop a risk
      scoring criteria that could target selectively the population most at risk. Late
      marriage, early age at first pregnancy and grand-multiparity significantly
      influenced the occurrence of cervical dyskaryosis. These factors may be valuable
      in developing a risk score that could target women at higher risk of developing
      cervical dyskaryosis.

PMID- 12521786
TI  - The use of porcine collagen in sling procedures for stress incontinence of urine.

PMID- 12521787
TI  - Bladder care after abdominal hysterectomy: a comparison of in-and-out versus
      continuous drainage.

PMID- 12521789
TI  - Gynaecology Case Reports.

PMID- 12521788
TI  - Obstetric Case Reports.

PMID- 12521792
TI  - Conference Diary.

PMID- 12521790
TI  - Abstracts from oral presentations to the Blair Bell Research Society meeting held
      at Liverpool Women's Hospital, 3-4 May 2001.

PMID- 12521793
TI  - Is fetal abdominal subcutaneous fat comparable with established indices of growth
      restriction?
AB  - The purpose of this study was to determine if measurement of the abdominal
      subcutaneous fat antenatally using ultrasound is comparable to other established
      indices of fetal growth restriction (FGR). One hundred women with singleton
      pregnancies had an ultrasound scan within 1 week of delivery at term. Ultrasound
      measurements included abdominal circumference (AC), liquor assessment by amniotic
      fluid index (AFI) and abdominal subcutaneous fat thickness (FAB). After
      delivery,infants were weighed and skinfold thickness at triceps and subscapular
      sites measured. Ponderal index was also calculated. Infants with an abdominal
      subcutaneous fat measurement antenatally of 5 mm or less (n = 41) were more
      likely than those with a fat measurement of more than 5 mm (n = 59) to have an
      AFI < 8 cm (P < 0.001) and to have an AC < 10th centile (P < 0.001). Decreased
      antenatal fat thickness was associated postnatally with a lower mean ponderal
      index (24.2 kg/m3 vs. 25.5 kg/m3, P < 0.02) and a decreased skinfold thickness
      (4.84 vs. 5.55 mm, P < 0.003 and 3.88 vs. 4.37, P < 0.03 for triceps and
      subscapular, respectively). This study shows that fetal abdominal subcutaneous
      fat measurement correlates with established predictors of fetal nutrition such as
      liquor volume, abdominal circumference, ponderal index, triceps and subscapular
      skinfold thickness.

PMID- 12521794
TI  - Clinico-pathological study of causes of perinatal mortality in a developing
      country.
AB  - Perinatal mortality rates are an important indicator of the overall obstetric and
      neonatal services available, and the socio-economic status of the community.
      These rates are also used to identify shortcomings in services provided. The aim
      of this study was to identify clinical causative factors of perinatal deaths
      (supported by post mortem evidence where possible). This was a prospective
      descriptive study. The total number of deliveries and perinatal deaths over a 6
      month period were recorded and clinico-demographic data noted. Post mortem
      examination information, if available, was also recorded. There was a total of
      7789 deliveries over the 6-month period and 460 perinatal deaths, giving a
      perinatal mortality rate of 59/1000 deliveries; 45% (n = 207) of the perinatal
      deaths had post mortem examinations. The mean age was 26 years; 84.8% were single
      mothers. One-third of the group were un-booked: the mean gestational age of fetal
      death was 31 weeks, and the mean birth weight was 1700 g. Two-thirds of the
      perinatal deaths were stillbirths. The leading obstetric causes of deaths were:
      abruptio placentae (25.3%), hypertension in pregnancy (24.9%), prematurity
      (17.4%), unexplained stillbirth (13.4%) and intrapartum asphyxia (9.2%). The
      perinatal mortality rate of 59/1000 deliveries is high. Although this is
      comparable with other developing countries, there is a need for improvement in
      organisation of obstetric and neonatal care, staffing levels and access to and
      effective utilisation of antenatal services. These will probably lead to a
      significant reduction of this relatively high perinatal mortality rate.

PMID- 12521795
TI  - Doppler dynamics: their clinical significance and relationship with fetal blood
      gases and pH measurements.
AB  - The aim of the study is to demonstrate the ability of abnormal Doppler indices to
      predict the acid-base status of the fetus. A pulsed Doppler study of umbilical
      artery, middle cerebral artery and thoracic aorta were assessed on 30
      intrauterine growth restricted and 27 appropriate-for-gestational-age fetuses
      immediately before cordocentesis. All the fetuses with absent end diastolic
      velocity in the umbilical artery were found to be acidemic by cordocentesis.
      Thoracic aorta pulsatility index (PI) increased and middle cerebral artery PI
      decreased significantly with increased umbilical impedance (r = 0.702, r = 
      0.340, respectively). Umbilical artery and thoracic aorta PI significantly
      increased, whereas middle cerebral artery PI decreased with a decrease in
      umbilical blood pH (r = -0.760, r = -0.642, r = 0.292, respectively). Doppler
      findings have a very strong correlation with the acid-base status of the fetuses.
      Increased umbilical impedance is associated with progressive impairment of
      placental gas exchange and that by the time diastolic flow is lost hypoxaemia or
      acidaemia is usually present.

PMID- 12521796
TI  - Lack of prenatal care in two different societies living in the same region and
      sharing the same medical facilities.
AB  - We set out to examine pregnancy outcome of women who utilised prenatal care
      facilities and those who did not, within two different ethnic groups living in
      the same region and sharing basically the same medical facilities. The study
      population consisted of all singleton deliveries occurring between the years 1990
      97 (n = 78 955). The analysis was based on a comparison of births to Jewish and
      Bedouin women who did not have prenatal care (defined as less than three visits
      at any prenatal care facility during the pregnancy) and those who had prenatal
      care (at least three visits at any prenatal care facility). Lack of prenatal care
      was found in 0.98% of the Jewish mothers and in 20.95% of the Bedouin women.
      Bedouin women receiving prenatal care had significantly higher rates of perinatal
      mortality (OR = 1.8, 95% CI 1.6-2.2; P < 0.001) and newborns weighing less than
      2500 g (OR = 1.2, 95% CI 1.2-1.3; P < 0.001) compared to their Jewish
      counterparts. However, in the comparison of women lacking prenatal care, no
      statistically significant differences were found between the groups with regard
      to those variables. In spite of the overwhelming cultural and socioeconomic
      differences between these societies, lack of prenatal care crossed social borders
      and a similar poor pregnancy outcome was found to be common in the two groups.
      Attempts should be made in order to remove barriers to prenatal care and to
      increase adequate utilisation of prenatal care in all societies in general and in
      ethnic minorities in particular.

PMID- 12521797
TI  - Pelvimetry: changing trends and attitudes.
AB  - Review of the literature regarding pelvimetry shows conflicting views as to its
      value. This study shows the decline in the use of pelvimetry in a teaching
      hospital obstetric unit over two time periods (1993 and 199798) and the change of
      views of the clinicians working in this unit. The number of pelvimetries
      performed fell from 56 per 1000 births to 4 per 1000 over this period. Most
      pelvimetries in 1993 (55.3%) were performed postpartum following caesarean
      section. However, in 199798, the majority (over 75%) were performed antepartum in
      breech presentation. The trend towards a more reluctant use of pelvimetry was
      mirrored by changes in clinicians' views. Recent publications and RCOG guidelines
      have effected a dramatic change in the use of pelvimetry over the last decade,
      largely restricting its use to a small selected group of patients.

PMID- 12521798
TI  - Trial of scar or elective repeat caesarean section at maternal request?
AB  - In a study between 1 January 1996 and 31 December 1998 at Watford General
      Hospital, we identified all women who booked having had a previous caesarean
      section. Data on age, social class and previous obstetric history was extracted
      from the notes, as was mode of delivery. Of the 718 patients identified, 497 were
      considered suitable for trial of scar. Of these 221 (44.5%) requested repeat
      caesarean section. Age, social class and indication for previous caesarean
      section could not predict those who accepted trial of scar. Of the 60 women who
      had had a previous successful trial of scar 59 (98.3%) underwent trial of scar
      and of the 48 who had had a vaginal delivery prior to caesarean section 37
      (77.1%) underwent trial of scar (P < 0.01). Maternal request for caesarean
      section, without obstetric contraindication to trial of scar, accounted for 24.9%
      of all the elective caesarean sections undertaken in our unit.

PMID- 12521799
TI  - Maternal depression and increased fetal activity.
AB  - Pregnant women with (n = 45) and without (n = 45) symptoms of depression (CES-D
      score of 16 or more) were provided ultrasound examinations during the second and
      third trimesters. An analysis of variance on the cross-sectional data yielded a
      significant diagnosis by gestational month interaction effect (P < 0.05). The
      fetuses of depressed mothers spent significantly more time being active during
      the fifth, sixth and seventh gestational months than fetuses of non-depressed
      mothers. A stepwise regression analysis revealed that 35% of the variance in time
      being active could be accounted for by the combined depression and trait anxiety
      scores of the mothers. These findings suggest that maternal depression correlated
      with increased fetal activity. These data also highlight the need for research on
      the potential effects of stress hormones on fetal activity.

PMID- 12521800
TI  - Prenatal diagnosis of translocation and a single pericentric inversion 9: the
      value of fetal ultrasound.
AB  - A total of 2741 high-risk pregnant mothers underwent invasive prenatal
      procedures, and in 94 of them (3.4%), fetal chromosomal or genetic anomalies were
      detected. In this study, we report on single pericentric inversions of chromosome
      9 as well as translocations, which constituted 32% (30 of 94) and 16% (15 of 94)
      of all identified chromosomal or genetic abnormalities, respectively. In six
      fetuses of the 30 with an inversion of chromosome 9, ultrasound findings were
      abnormal and consisted of hydramnios, anhydramnios, hydroureter, hydronephrosis,
      encephalocele and prune belly syndrome, occurring singly or in combination. Among
      the 15 fetuses with chromosomal translocations, five had sonographic
      abnormalities. In conclusion, we found detailed ultrasound survey of fetuses with
      either translocations or inversions of chromosome 9 to be an additional source of
      useful information concerning fetal status that could be of value in genetic
      counselling of affected parents.

PMID- 12521801
TI  - Teenage pregnancy: still an obstetric risk.
AB  - A 30-month retrospective and comparative study of the obstetric performance of
      teenagers and females between 20 and 24 years was performed at Nnamdi Azikiwe
      University Teaching Hospital, Nnewi, Nigeria. The prevalence of teenage birth was
      21.8 per 1000 deliveries. Females aged 2024 years performed better than teenagers
      with respect to booking status, marital status, preterm delivery, low birth
      weight and perinatal morbidity. There was no difference with respect to pre
      eclampsia caesarean section and perinatal mortality. Teenage birth is still an
      obstetric risk factor. There is need to foster the advocacy and reproductive
      health programmes against adolescent pregnancy and teenage marriage.

PMID- 12521802
TI  - Determinants of mission house delivery among booked patients in a Nigerian
      teaching hospital.
AB  - This study examines the determinants of Mission House Delivery among booked
      patients in Ile-Ife, Nigeria. During the 12 months of the study (1 May 199930
      April 2000) 196 booked patients at Obafemi Awolowo University Teaching Hospitals
      Complex, Ile-Ife who delivered at mission houses were analysed. All ages and
      parity groups, educational level and social classes were involved. The majority
      (73%) were of low socio-economic class. The reasons for mission house delivery
      included financial constraints (41%), fear of possible caesarean section (46%),
      industrial action by health-care workers (39%), transport difficulty at night
      (26%), previous deliveries in mission houses (16%) and communal feud (12%). Four
      maternal deaths occurred (MMR 978/100 000 births) and 20 perinatal deaths (PNMR
      118/1000 total births). Reduction of hospital user fees, provision of
      transportation and efficient telecommunication facilities at all times, conflict
      resolution and proper remuneration of health care workers are urgent needs to be
      addressed. Legislation against delivery in unsafe places and establishment of
      appropriate facilities by churches interested in maternity services is highly
      recommended.

PMID- 12521804
TI  - A plea for data on the sex ratio of infants associated with the HELLP syndrome.

PMID- 12521803
TI  - Human parvovirus B19 infection during pregnancy and its possible impact on
      perinatal outcome in the obstetric population of Kuwait.

PMID- 12521805
TI  - Improving outcomes in gynaecological cancer: the impact of centralisation on
      patient flows and service provision.
AB  - Responses to a postal questionnaire and cancer registry data were utilised to
      evaluate the impact of the recent NHS Executive guidelines for the management of
      gynaecological malignancies on patient flows and service provision in the West
      Midlands. They were also used to assess the service provision in the west
      midlands in relation to these guidelines. Eighty-nine per cent (16/18) trusts
      returned completed questionnaires. Seventy-two per cent (46/64) of
      recommendations were achieved by all four centres; 18% (10/57) by all 12 units.
      The cancer registration data revealed 404 cases that would need to be transferred
      to the cancer centres per annum in order to implement the guidelines. A more
      detailed analysis for the northern area of the region estimated that a further
      120 cases per annum would need to be managed at the main centre. This study has
      shown that implementation of the guidelines will require significant shifts in
      patient flows. This will increase workloads for the cancer centre and have an
      impact on service provision and resource allocation.

PMID- 12521806
TI  - Clinical evaluation of borderline nuclear changes in cervical smears at
      colposcopy and biopsy.
AB  - The aim of this study was to determine the incidence of cervical intraepithelial
      neoplasia at colposcopy and biopsy in woman with smears showing borderline
      nuclear changes to assess the predictive rate of colposcopy in identifying CIN
      and to verify the importance of follow-up. A retrospective study of 134 cases
      referred for colposcopic assessment with borderline nuclear changes in smears was
      carried out. Of the 134 patients studied, 44.8% had cervical intraepithelial
      neoplasia and 30% had benign changes of the cervix; 25.5% of cases were normal,
      14% of the study population had HPV infection confirmed by biopsy. Of all cases
      of CIN, 38% were diagnosed to have low grade abnormalities, 6.8% had high-grade
      abnormalities. The predictive rate of colposcopy in identifying low-grade
      abnormalities was approximately 60% and 80.7% had a normal smear after 6 months,
      follow-up. As cervical intraepithelial neoplasia was found in a significant
      number of patients, borderline changes in cervical smears need subsequent
      evaluation. Even though more than two-thirds of women had negative smears at 6
      month follow-up, the study recommends annual follow-up smears for several years
      as the long-term risk is not definitely known.

PMID- 12521807
TI  - The management of endometriosis: a survey of patients' aspirations.
AB  - The aim of this study was to determine the aspirations of women with
      endometriosis in terms of the management of their disease. We interviewed 32
      women with confirmed endometriosis and asked them to discuss the potential
      benefits of the establishment of a specialist endometriosis clinic. Eighty-eight
      per cent of the participants agreed that a separate specialist clinic would be
      beneficial. The reasons they cited can be grouped under four main themes:
      information provision, quality and type of care, peer support and endometriosis
      awareness. On the basis of these responses we propose that a strategy utilised in
      the management of other chronic diseases, drop-in group medical appointments, may
      provide a way forward. In addition, on the basis of the range of symptoms
      reported by our participants, we would argue that a multidisciplinary approach is
      necessary if endometriosis management is to be effective.

PMID- 12521808
TI  - Perioperative morbidity of hysterectomy for benign gynaecological disease.
AB  - This study reviews the perioperative surgical and associated morbidity of
      abdominal and vaginal hysterectomy for benign gynaecological disease. Over a 5
      year period, 199296, there were 2088 hysterectomies; 1244 (60%) abdominal and 844
      (40%) vaginal. The surgical morbidity for abdominal hysterectomy (6.2%) was twice
      that of vaginal hysterectomy (3.2%). The associated morbidity for abdominal
      hysterectomy (4.0%) was four times that of vaginal hysterectomy (0.9%).
      Additional surgical procedures (other than salpingo-oophorectomy) performed at
      the time of hysterectomy increased morbidity by 20% in association with abdominal
      hysterectomy and by 46% with vaginal hysterectomy. Serious morbidity associated
      with hysterectomy for benign disease was low.

PMID- 12521809
TI  - The potential effect of controlled ovarian hyperstimulation on follicular
      vascular perfusion: a study applying power Doppler ultrasonography within a
      treatment programme using donor sperm.
AB  - This was a prospective observational study to evaluate the effect of controlled
      ovarian hyperstimulation on follicular vascularity. A subjective grading system
      was applied to assess vascularity using transvaginal power Doppler
      ultrasonography on the day of insemination (32-36 hours post-HCG administration)
      in donor treatment cycles undergoing either controlled ovarian hyperstimulation
      (COH group) with gonadotrophin and intrauterine insemination or intracervical
      insemination with/without clomiphene stimulation (non-COH group). The incidence
      of follicles (81% vs. 53%; P < 0.05) as well as cycles (63% vs. 49%; P < 0.05)
      with uniformly high grade vascularity was significantly higher in treatments that
      had controlled ovarian hyperstimulation compared with unstimulated or clomiphene
      induced donor cycles. Pregnancy rates were higher and early pregnancy loss rates
      lower, in cycles with uniformly high grade follicular vascularity in both
      treatment groups compared with other vascularity grades. Using multiple logistic
      regression analysis, the only independent variable that was significantly related
      to pregnancy rates in this treatment programme was follicular vascularity.
      Controlled ovarian hyperstimulation appears to have an effect on follicular
      vascularity and this may contribute to improved outcome in donor insemination
      treatment programmes.

PMID- 12521810
TI  - The place of autotransfusion in management of ectopic pregnancy--10 years
      experience.
AB  - Between the period January 1989 to December 1998, a total of 119 cases of ectopic
      gestations and 11 389 deliveries were managed. The incidence of ectopic gestation
      was 1.04%, or one in 96 deliveries. Tubal gestation constituted 97.47% (n = 116),
      while abdominal and ovarian gestation were 1.68% (n = 2) and 0.84% (n = 1)
      respectively. The age range was 16-42 years, with mean age of 27 years. The modal
      age group was 26-30 years; 10.18% (n = 12) were associated with intrauterine
      contraceptive devices. Abdominal pain was the most common symptom in 96% (n = 98)
      while abdominal and cervical excitation tenderness occurred in 97.10% and 72.6%,
      respectively. Autotransfusion was used in correction of anaemia in 62.75% (n =
      64) while 37.25% (n = 38) received both autotransfusion and donated homologous
      blood. Maternal death rate was 0.84% (n = 1).

PMID- 12521811
TI  - Comparative diagnostic values of grey-scale USS versus CT scan in the primary
      management of gynaecological pelvic mass with emphasis on ovarian cancer
      detection and staging.
AB  - Thirty-one consecutive patients with clinical pelvic masses suspected to be
      gynaecological in origin were initially investigated by transabdominal grey-scale
      ultrasound (TAUS) and then by computed tomography (CT) prior to surgery and or
      chemotherapy. Retrospective comparative review of the reports of the two imaging
      methods was carried out on each patient and then correlated with surgical
      findings and histopathology report. The diagnostic potentials of the two imaging
      methods with respect to ovarian cancer detection and staging were particularly
      emphasised. The results were analysed and compared with published results of
      similar studies in the literature. Compared with TAUS we found CT scan more
      sensitive in making an overall presumptive diagnosis of pelvic mass (15/31, 48%
      vs. 9/31, 29%). The sensitivity of CT scan for all ovarian cancer detection was
      greater than that of TAUS (5/6, 83% vs. 4/6, 67%) but TAUS was more specific. The
      false negative and false positive values for cancer detection were comparable.
      Both methods were equally efficacious in detecting and staging advanced ovarian
      cancer cases (4/4, 100%). Visualisation of the ovaries occurred more readily with
      TAUS, which in addition offered a more precise assessment of ovarian tumour size.
      There were no significant differences in the two methods regarding tumour
      localisation (organ of origin), characterisation and the details of descriptive
      report when no presumptive diagnosis is offered. Overall CT did not offer
      significant additional features and did not result in changes in management plan
      in any of the patients reviewed. The marginal benefit of CT scan over TAUS will
      not warrant its routine usage in the diagnosis of gynaecological pelvic mass. Our
      findings largely reflected the conclusions of published reports in the
      literature.

PMID- 12521812
TI  - To peritonealise or not to peritonealise? A randomised trial at abdominal
      hysterectomy in Iran.
AB  - We conducted a trial to determine whether non-closure of the visceral and
      parietal peritoneum alters the intraoperative or post-operative course at
      abdominal hysterectomy. This was a parallel-group double-blind randomised
      controlled trial was performed on 66 women who underwent abdominal hysterectomy
      with or without salpingo-oophorectomy. Twenty-seven were allocated to the control
      'closed' group and 39 women to the study 'open' group. The main outcome measures
      were operative time, estimated blood loss, postoperative pain assessed by visual
      analogue scale and amount of postoperative analgesia. The study was conducted in
      the Department of Gynecological Oncology in a university teaching hospital. The
      operative time was shorter (P < 0.05) and the time to ambulation without
      assistance was significantly shorter in study group. There were no difference in
      postoperative pain, blood loss, amount of postoperative analgesia and antibiotics
      in the two groups. Peritoneal closure at abdominal hysterectomy provides no
      immediate postoperative benefits while unnecessarily lengthening surgical time
      and anaesthesia exposure. We suggest that the traditional practice of visceral
      and parietal closure be abolished at abdominal hysterectomy.

PMID- 12521813
TI  - Treatment of the twisted cystic ovary with normal blood flow by simple
      aspiration.
AB  - Simple aspiration was performed in eight patients to correct torsion of cystic
      ovaries with normal blood flow, imaged by the colour Doppler technique. Abdominal
      pain resolved spontaneously following aspiration. Symptoms recurred in three
      patients, necessitating detorsion by laparoscopy. Normal follicular growth was
      assessed within 3 months in the non-pregnant patients.

PMID- 12521815
TI  - Obstetric Case Reports.

PMID- 12521814
TI  - Does cigarette smoking cause detrusor instability in women?

PMID- 12521816
TI  - Gynaecology Case Reports.

PMID- 12521817
TI  - Correspondence.

PMID- 12521818
TI  - Abstracts from oral presentations to the Blair Bell Research Society meeting held
      at St Mary's Hospital, London on 21 September 2000.

PMID- 12521820
TI  - Conference Diary.

PMID- 12521821
TI  - Treatment for chronic, mild-to-moderate hypertension and pregnancy: what does the
      evidence say?

PMID- 12521822
TI  - Cardiovascular oestrogen effects in women.

PMID- 12521823
TI  - Preliminary experience with the use of insulin lispro in pregnant diabetic women.
AB  - Insulin lispro (IL) possesses characteristics (decreased hypoglycaemia, greater
      convenience in timing of administration and better post-prandial glucose control)
      which may favour its use in women with diabetes. We report pregnancy outcomes in
      seven women with Type I diabetes treated with IL. Mean age was 30 years (2241),
      duration of diabetes from 3 to 21 years. Two were using IL pre-conception; others
      transferred at various stages of pregnancy. Mean daily dose of IL within the last
      month of pregnancy ranged from 0.59 to 1.13 U/kg. Mean HbA1C from 4.4 to 8.5%.
      Babies were delivered at 3438 weeks' gestation, birth weights from 2900 to 4125 g
      (mean 3434 g). There were no congenital abnormalities. All patients elected to
      continue with IL after pregnancy. Our experience suggests that IL is convenient
      and practical therapy for women with Type I diabetes in pregnancy.

PMID- 12521824
TI  - Shoulder dystocia: risk factors and maternal and perinatal outcome.
AB  - Shoulder dystocia (S.D.) is an obstetric emergency which may be catastrophic for
      both mother and baby. The aims of this study were to determine the incidence of
      S.D., the maternal and perinatal outcome, and which risk factors were important.
      This was a retrospective review of all cases of S.D. during 1997 and 1998.
      Controls were selected as the next vaginal delivery following the S.D. case,
      matched for age, parity and gestation at delivery. Risk factors were compared
      between the two groups. There were 54 cases of S.D. over the study period, an
      incidence of 0.57% of 9541 vaginal deliveries. There were significant differences
      between cases and controls in birth weight, active phase of 1st stage of labour,
      2nd stage of labour, episiotomy rate, third-degree tear rate, admission to SCBU
      and trauma to the baby at delivery. There were two infants with fractured
      clavicle and two with Erb's palsy.

PMID- 12521825
TI  - Pregnancy outcome of patients with previous four or more caesarean sections.
AB  - Between 1994 and 1999, of the 44 357 mothers delivered at the Riyadh Armed Forces
      Hospital (RAFH), 255 patients had four or more previous caesarean sections (CS).
      This comprised 0.5% of the obstetric population. One hundred and eighty-nine
      (74%) had four, 52 (20%) five, 12 (5%) six and two (0.4%) patients had seven CSs.
      Adhesions were severe in 128 (50%), moderate in 18 (7%), mild in 81 (32%) and no
      adhesions in 28 (11%) cases. The incidence of placenta praevia was five times
      that of the overall obstetric population (2.4% vs. 0.5%). One case of uterine
      rupture occurred, an incidence of 4/1000 cases. The incidence of placenta praevia
      rises with rising CS rate. Patients with multiple CS and placenta praevia should
      be counselled regarding the possibility of caesarean hysterectomy. Repeat CS is
      safe and tubal ligation should be advised, but not forced as it is not an
      absolute indication for sterilisation.

PMID- 12521826
TI  - Has consanguinity any impact on occurrence of pre-eclampsia and eclampsia?
AB  - In this study we tested the hypothesis of an association between consanguinity
      and pre-eclampsia/eclampsia. This is a case-control study conducted at Princess
      Badea Teaching Hospital, Irbid-Jordan during the period May 1997-April 1998. The
      study population were Jordanian women delivered at Princess Badea Teaching
      Hospital with or without hypertensive disorders of pregnancy. The total number
      was 208 pre-eclamptic/eclamptic women (76 primiparous and 132 multiparous) and
      618 randomly selected non-hypertensive women. In primiparous as well as
      multiparous women, it was evident that neither consanguinity nor the degree of
      the relationship to the husband in consanguineous marriages had an impact on the
      incidence of preeclampsia/eclampsia. However, comparing the incidence of
      consanguinity between pre-eclamptic/eclamptic and non-hypertensive, multiparous
      women married to a relative other than first cousin, the P value was 0.0248,
      which we explained as chance incidence. When we compared the incidence of
      consanguineous marriages as a whole between pre-eclamptic/eclamptic and non
      hypertensive, multiparous women, there was no evidence of any impact of
      consanguinity on the incidence of pre-eclampsia/eclampsia.

PMID- 12521827
TI  - Grandmultiparity--trends and complications: a study in two hospital settings.
AB  - Pregnancy after the fifth delivery is viewed with anxiety, especially by
      obstetricians in developing countries working with inadequate facilities. High
      parity is still common with serious consequences to the fetus, the mother, the
      family and society. In the last 40 years, non-governmental, national and
      international efforts have been made to reduce fertility rates. We therefore
      intended to determine the trend in the grandmultiparity rates from 1 January 1987
      to 31 December 1994 in the South Western part of Nigeria. The obstetric
      performance of these grandmultiparae in two different settings were to be
      compared. This was a retrospective, case-note analysis of all the grandmultiparae
      delivered at the University College Hospital (UCH) (Group A) and the Oluyoro
      Catholic Hospital (OCH) (Group B), both in Ibadan city. The former is a tertiary
      health care centre while the latter is a secondary centre. The socio-clinico
      demographic characteristics of these patients were collated and analysis and
      comparison performed using EPI-INFO software. In Group A, 828 grandmultiparae
      were seen among 9215 deliveries, a rate of 8.99% (10.90% in 1987 to 3.36% in
      1994). In Group B, there were 1940 cases among 22 587 deliveries, i.e. 8.59%
      (12.75% to 6.07%), respectively. The modal age group was 31-35 years, and women
      above 35 years formed one-third of cases. The parity group 5-7 was the most
      frequent in both groups (91.6% vs. 94.9%). Only two mothers (both in group B) had
      parity above 10. Booked patients formed a larger percentage in Group B than in
      Group A (85.8% vs. 69.7%, respectively). In Group B 85.9% had spontaneous vertex
      delivery as opposed to 66.3% in Group A. Caesarean section was the mode of
      delivery in 9.0% and 24.2% in Groups B and A, respectively. Equal percentages had
      breech delivery. The modal birth weight was 2.51-3.00 kg in both groups.
      Macrosomic babies formed 3.7% in Group A and 2.4% in Group B, while low birth
      weight babies formed 17.7% and 11.7% in Groups A and B, respectively. The crude
      perinatal death ratio was 123/1000 in Group A and 68/1000 in Group B. Antepartum
      haemorrhage, anaemia and premature rupture of membranes in Group A and anaemia,
      hypertension and antepartum haemorrhage in Group B were the most common pregnancy
      complications noted. In labour, abnormal lie/presentation, prolonged labour and
      premature labour in Group A and abnormal lie/presentation, antepartum haemorrhage
      and birth asphyxia in Group B formed the majority of the complications. The most
      common puerperal complications were primary postpartum haemorrhage, wound/genital
      sepsis in Group A and anaemia and primary postpartum haemorrhage in Group B,
      respectively. Maternal death ratio was 10.85/100 000 total deliveries in Group A
      and 35.42/100 000 in Group B. High parity is still common in developing
      countries, although the incidence is declining, with rates of 3.4% and 6.1% of
      total deliveries in Groups A and B, respectively. More patients are delivered per
      abdomen at UCH compared to OCH. The perinatal mortality rate is higher at UCH
      than OCH but the maternal mortality rates follow the reverse. Recommendations are
      made concerning the reduction in high parity rates and its associated
      complications.

PMID- 12521828
TI  - Fetal magnetocardiogram recordings and power spectra analysis in biomagnetic
      arrhythmic signals.
AB  - In this study we investigated fetal arrhythmias using a Superconductive Quantum
      Interference Device (SQUID) in a shielded environment of low magnetic noise. The
      subjects involved were 84 pregnant women, 1941 years old (mean=30.55, SD=7.18)
      with single normal uncomplicated pregnancies and gestational ages 2532 weeks and
      68 pregnant women 2342 years old (mean=32.89, SD=5.28), treated with ritodrine
      for the risk of preterm labour; with gestational ages 2635 weeks. Fourteen
      fetuses were found with cardiac arrhythmia six cases with tachycardia, one with
      bradycardia and seven with supraventricular/ ventricular (S/V) extrasystoles.
      Power spectra analysis of fetal magnetocardiographic arrhythmic signals assesses
      the functional state of their autonomic nervous system. Thus, magnetocardiography
      and power spectral analysis of the arrhythmic signals inform us that there is no
      deviation in the physiological process of the fetal heart in cases of fetal
      arrhythmia.

PMID- 12521829
TI  - Maternal request for caesarean section: is it obstetrician driven?
AB  - To assess whether maternal request for elective caesarean section was in fact
      obstetrician driven a postal questionnaire was undertaken in the North Thames
      Region. One hundred and thirtyfour consultants who undertook NHS obstetrics
      replied to the questionnaire. Only one (0.8%) offered elective caesarean section
      to all women, and all suggested trial of scar in selected cases. Eighty-three
      (61.9%) of respondents felt that maternal request had significantly increased
      their caesarean section rate. It is concluded that maternal request for caesarean
      section is not obstetrician led, but patient driven.

PMID- 12521830
TI  - Three decades of acquired gynaetresia in Ibadan: clinical presentation and
      management.
AB  - A retrospective analysis of acquired gynaetresia (Vaginal Stenosis) managed at
      the University College Hospital Ibadan, Nigeria between 1967 and 1996 was
      conducted in terms of clinical presentation and management. The prevalence rate
      was 7/1000. The peak age incidence was 20-30 years. Chemical vaginitis resulting
      from insertion of caustic vaginal pessaries for various reasons was the major
      cause of acquired gynaetresia. Dyspareunia/apyreunia and vaginal
      stenosis/occlusion were the most common symptoms and clinical findings
      respectively. The various surgical treatment of acquired gynaetresia included one
      stage vaginoplasty, McIndole-Read's two stage vaginplasty, separation of labial
      agglutination, Williams's operation, and simple dilatation of the vagina.
      Successful correction was recorded in 68% of the patients while 28% had residual
      partial stenosis, 4% had complete stenosis and 6% were lost to follow-up. It was
      concluded that acquired gynaetresia is preventable. Efforts should be made by
      authorities to address this issue and create designated centres in the country
      for the management of these cases and training of junior gynaecologists.

PMID- 12521831
TI  - Refining surgical technique to prevent occurrence of vault haematoma after
      vaginal hysterectomy.
AB  - We set out to analyse the effect of refinement of incision and closure technique
      of the vaginal vault on the incidence of vault haematoma after hysterectomy. All
      the surgery was performed in the Gynaecology Department, Benenden Hospital, Kent,
      UK. This was initially a retrospective study followed by a prospective analysis
      of postoperative morbidity related to vaginal vault haematomas and critical
      review of surgical technique over 5 years in all cases undergoing vaginal
      hysterectomy within our unit. Following refinement in surgical technique a
      significant reduction in the incidence of clinically significant vaginal vault
      haematomas from 15.7% to 1.7% (P<0.001) was observed over a 4-year period.
      Adoption of the described surgical techniques is recommended to minimise the risk
      of clinically significant vaginal vault haematomas after vaginal hysterectomy.

PMID- 12521832
TI  - Vaginal oestradiol for the treatment of lower urinary tract symptoms in
      postmenopausal women--a double-blind placebo-controlled study.
AB  - A prospective randomised double-blind placebo-controlled trial of 17-beta
      oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in
      110 postmenopausal women with urinary frequency, urgency and/or urge incontinence
      recruited from a tertiary referral urogynaecology clinic. After 3 months the only
      statistically significant difference was a greater reduction in urinary urgency
      in those women with sensory urgency treated with 17-beta oestradiol compared to
      placebo. This may be due to the effective treatment of local vaginal atrophy by
      low-dose oestrogen rather than any effect on the lower urinary tract.

PMID- 12521833
TI  - Setting up a one-stop mifepristone-misoprostol medical termination of pregnancy
      service for all gestations from 5 to 23 weeks--a review of 482 cases.
AB  - Mifepristone-misoprostol combination is increasingly being utilised for medical
      termination of pregnancy on account of its reported efficacy, safety and lower
      cost. Experience with this modality of effecting termination of pregnancy from 9
      to 13 weeks' gestation is scanty. At the Scunthorpe General Hospital in the
      United Kingdom, we established a nurse-led, one-stop medical termination of
      pregnancy service using mifepristone and misoprostol for all gestations from 5 to
      23 weeks. A review of the case records of 482 women who had medical termination
      of pregnancy at all gestations from 5 to 23 weeks from December 1997 to May 1999
      was undertaken in order to assess the effectiveness and complications associated
      with the mifepristone-misoprostol protocol. Complete abortion was achieved in 406
      (84%) women. Surgical evacuation was required to complete the abortion in 74
      (16%) women. The complete abortion rate was similar across the spectrum, i.e. 87%
      in the 5- 8-weeks group; 79% in the 9-13 weeks group; and 87% in those of > or =
      14 weeks. Two failures occurred: one of them proceeded to surgical evacuation
      after three courses of misoprostol, while the other continued with her pregnancy
      after one course. Three women (0.6%) required blood transfusion for haemorrhage,
      while two others were treated for infection. Oral mifepristone with or without
      vaginal misoprostol in an effective and safe regimen for termination of all
      pregnancies from 5 to 23 weeks' gestation.

PMID- 12521834
TI  - A review of gynaecological cancer management: a large West Midlands general
      hospital experience.
AB  - The records of 372 women with gynaecological cancer were reviewed to assess the
      quality of care which has been given and to compare the standards achieved with
      those suggested by The West Midlands Gynaecological Oncology Group. The median
      primary referral interval was 18 days; 54% of patients were seen within 2 weeks
      of referral. The median interval between first hospital visit and surgery was 32
      days and 77.5% of patients had their operation within 8 weeks. The median
      interval between histology report and starting adjuvant therapy was 19 days and
      81% of patients commenced treatment within 6 weeks. The histological diagnosis
      was available within 2 weeks of surgery in 77% of patients. Less than one-third
      of patients in our series were referred to the lead consultant of gynaecological
      oncology, who performed 50% of the operations for gynaecological malignancy.
      There was no record of the primary referral interval, date of surgery and date of
      commencement of adjuvant therapy in 35%, 25% and 20% of patients, respectively.
      More attention must be given to redistribution of caseload with more involvement
      of the gynaecological cancer team and to improvement in clinical cancer data
      collection to decrease the extent of missing data. The delays in referral of
      patients with suspected gynaecological malignancy could be minimised by improving
      communication between the general practitioners and the hospitals.

PMID- 12521835
TI  - Findings in women with postmenopausal bleeding investigated with hysteroscopy.
AB  - Most reports on histopathological findings of postmenopausal bleeding were
      published before hysteroscopy was widely used. Recent studies have shown that
      hysteroscopic examination is better than dilatation and curettage alone in
      detecting intrauterine pathology. The aim of this study is to assess
      histopathological findings of patients presented with postmenopausal bleeding
      after incorporation of hysteroscopic examination. Between 1 January 1996 and 31
      December 1996, a total of 199 consecutive patients presenting with postmenopausal
      bleeding to a regional hospital were reviewed. Patients were investigated with
      cervical biopsy, endometrial aspiration or hysteroscopy and curettage. Excluding
      patients who had hysterectomy and cervical cancer, 97% of the patients had
      hysteroscopic examination. The majority of patients with postmenopausal bleeding
      had atrophic vaginitis and/or atrophic endometrium (58.8%). Other common
      diagnoses were endometrial polyp (9.4%), endometrial carcinoma (9.4%) and
      carcinoma of the cervix (6%). Other diagnoses included submucous fibroid,
      endometrial hyperplasia, pyometra, ovarian cancer and urethral caruncle.
      Pathologies found were similar to early reports, except that incidences of
      submucous fibroids and endometrial polyps were higher (13.4%). We concluded that
      all patients with postmenopausal bleeding should be investigated thoroughly as
      22% have significant pathology. Hysteroscopy is the preferred investigation
      because of high incidences of endometrial polyps and submucous fibroids.

PMID- 12521836
TI  - An audit of patients investigated by laparoscopy and dye for infertility.
AB  - We reviewed 100 laparoscopy and dye studies performed in the Coombe Women's
      Hospital to determine whether recommended guidelines were followed for the
      investigation of infertility. Individual chart review provided information on
      patient demographics, preoperative investigations, operative findings and
      outcome. Preoperative assessment of ovulation or a semen analysis was not
      performed in 20 and 30 women, respectively. At laparoscopy bilateral tubal
      patency was demonstrated in 86 patients, three patients had bilateral blocked
      tubes and 11 patients had unilateral tubal occlusion. In 54% of patients there
      were no other additional findings. Following laparoscopy five women were referred
      for in vitro fertilisation and five patients had further surgery as a result of
      the findings at laparoscopy. In addition, three women were treated for
      hyperprolactinaemia and three male partners were referred for further
      investigation. Within one year 20 women became pregnant, 18 delivered a baby and
      two had a miscarriage.

PMID- 12521837
TI  - Laparoscopic 'oophorectomy-in-a bag'--an alternative to laparotomy for the
      evaluation of suspicious ovarian masses.
AB  - A prospective observational study was performed to assess the feasibility of the
      technique of laparoscopic 'oophorectomy-ina bag' for the safe removal of ovarian
      masses that do not meet the standard guidelines for laparoscopic management of
      adnexal pathology. Ovarian lesions were selected preoperatively by: age of the
      patient, ultrasound appearance, bilaterality and size. None of the women had
      ascites or matted bowel on ultrasound, and all had normal serum tumour markers.
      There were no stigmata of malignant disease in any of the cases at the time of
      surgery. Twenty women were recruited. Eighteen procedures (90.0%) were completed
      successfully laparoscopically. In two cases the bag could not be removed
      laparoscopically and minilaparotomy was performed. Nineteen of the tumours
      (95.0%) were removed without intra-abdominal spillage; the bag ruptured in one
      case. There were no major complications. One case of borderline ovarian tumour
      (stage Ia) was discovered. We conclude that laparoscopic 'oophorectomy-in-a bag'
      allows for the safe removal of suspicious ovarian tumours. The advantages of this
      approach are that women can be treated locally, a laparotomy is avoided, and the
      subgroup with ovarian malignancy can be identified to be referred to an
      oncological centre.

PMID- 12521838
TI  - Laparoscopic methotrexate instillation in unruptured tubal pregnancy--is it
      worthwhile?
AB  - This study documents the success rate and risks of laparoscopic local injection
      of methotrexate in the unruptured tubal pregnancy. This was a prospective study
      conducted in two centres, King Abdulaziz University Hospital and Dr Erfan &
      Bagedo Hospital, Jeddah, Saudi Arabia. Twenty-one patients with an intact tubal
      pregnancy were selected for laparoscopic local treatment with the use of a single
      injection of 12.5 mg of methotrexate into the ectopic site at the time of
      diagnostic laparoscopy. In 80.9% (17 patients), serum beta-hCG level decreased to
      the nonpregnant level with no further intervention and the patients recovered
      without any serious side effect. In 19.9% (four patients) mini-laparotomy was
      indicated because of a rising beta-hCG. Local methotrexate therapy in an early
      intact tubal ectopic at the time of laparoscopy is a possible alternative to
      surgery in selected cases. It also has some advantage over systemic
      (intramuscular) methotrexate as it avoids potentially serious side effects.

PMID- 12521839
TI  - Hydatidiform mole in Ile-Ife, Nigeria: a 10-year review.
AB  - The aim of this study was to review the demographic characteristics, clinical
      presentation and management outcome in patients with hydatidiform mole at Obafemi
      Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. Case-notes of 46
      patients with histologically confirmed diagnosis of hydatidiform mole over a 10
      year period were obtained and relevant information analysed. The incidence of
      hydatidiform mole was 2.4 per thousand maternities. The most common presenting
      symptom was vaginal bleeding occurring in all the cases, while anaemia defined as
      Hb <10 gm/dl was the most common complication. There were four maternal deaths in
      this study, given a case fatality of 8.7%. Hydatidiform mole in this review was
      associated with unusually high morbidity and mortality mainly due to late
      presentation, although epidemiology and clinical features were essentially as for
      previous studies.

PMID- 12521844
TI  - ERRATUM.

PMID- 12521840
TI  - Failed sterilisation, a continuing problem for the gynaecologist?

PMID- 12521845
TI  - Conference Diary.

PMID- 12521846
TI  - How discriminatory is the objective structured clinical examination (OSCE) in the
      assessment of clinical competence of medical students?
AB  - A prospective collection and analysis of examination marks for three consecutive
      academic years was undertaken to determine the correlation between the objective
      structured clinical examination (OSCE) and various other components of medical
      students' examination, and also to examine how discriminatory the OSCE
      examination is in the assessment of clinical competence. Out of 388 students,
      96.3% passed the examination at the first attempt. Of those who passed, 15.5% had
      merit while 1.0% had a distinction. When the OSCE component was excluded from the
      analysis, 11.6% and 2.8% had merits and distinctions, respectively, but when the
      clinical examination was excluded, there were 17.8% and 6.2% merits and
      distinctions, respectively. Correlations between the various components of the
      examination were significant except for that between the clinical examination and
      the project. Although the OSCE and clinical components of examinations for
      clinical students are complementary, the OSCE component awards more merit and
      distinction categories. Although there were statistically significant
      correlations between the various components of the examination, only 11% of the
      variability in clinical examination scores could be explained by the performance
      in OSCE suggesting that the different components are testing different aspects of
      the student's clinical competence. Completely replacing clinicals with an OSCE
      may not necessarily be the best way of assessing medical students' clinical
      competence.

PMID- 12521847
TI  - Leptin levels in the obese African parturient.
AB  - Prolactin, HCG and oestrogen are reported to have a role in regulating serum
      leptin levels and therefore adiposity in pregnancy. The aim of this study was to
      determine serum leptin levels during pregnancy in African women, and was
      conducted in the Antenatal Clinic, King Edward VIII Hospital, Durban, South
      Africa. Eighty-two obese and non-obese women were studied. Demographic details
      and anthropometric measurements were recorded, and serum leptin levels determined
      by radio-immunoassay in all women. Age, parity and gestational age showed a weak
      correlation with leptin levels. Weight (4=0.6); body mass index (r=0.5), and the
      circumference of midarm (r=0.4), waist (4-0.6, hip (5=0.5) and thigh correlated
      positively with leptin values. Serum leptin values in African pregnant women are
      not dissimilar to that of studies in other racial groups.

PMID- 12521848
TI  - The risk of rupture of the uterus: an analysis of 1086 births after previous
      caesarean section.
AB  - In the work presented here, obstetric management after a previous caesarean
      section was studied in a large patient group at the University Department of
      Gynecology and Obstetrics in Cologne from 1979 to 1995. Particular attention was
      given to the feared complication of uterine rupture. From a total of 15 166
      deliveries, 1086 of the births had been preceded by one or more caesarean
      sections. These 1086 births formed the basis for the present study. Vaginal
      delivery was attempted in 44.5% of patients and was successful in 86% of those
      cases. Where there had been only one previous caesarean section, the percentage
      shifted in favor of vaginal delivery. All patients with more than two previous
      caesarean sections were delivered by elective caesarean section. The feared
      complication of rupture of the uterus occurred in four cases, for which case
      reports are presented. In view of such cases, signs of imminent uterus rupture
      often constitute an indication for elective (11.5%) or emergency resectioning
      (31.9%). No relationship was found between fetal outcome and mode of delivery.
      This retrospective study confirms the general recommendation and safety of
      vaginal delivery after a previous caesarean section as long as risks are
      minimised by a readiness to proceed with a repeat caesarean when signs of
      imminent rupture of the uterus arise.

PMID- 12521849
TI  - Caesarean section delivery in Trinidad.
AB  - A 7-year retrospective survey was conducted in order to determine local trends in
      caesarean section rates, maternal outcome and indications for the procedure. The
      annual rate of caesarean births has not exceeded 10.0% of deliveries. The overall
      rate, at 7.4% for the period of study, was not significantly different from that
      obtained a decade and a half ago. Significant procedure-related morbidity was
      uncommon. In view of preventable anaesthetic maternal deaths, a plea is made for
      an increased use of regional in preference to general anaesthesia in selected
      cases.

PMID- 12521850
TI  - Induction of labour: a comparison of two methods with particular concern to
      patient acceptability.
AB  - Induction of labour is a common obstetric intervention. When the cervix is
      unfavourable ripening agents are used, commonly prostaglandin E2. There are
      several methods of administration of prostaglandin E2 and little comparative work
      has been performed as to their acceptability by patients. Patients undergoing
      induction of labour by prostaglandin E2 were randomised to receive either
      intravaginal gel or an intravaginal slow-release pessary. Patient satisfaction
      with the method received was then assessed. Sixty-nine patients were randomised,
      34 to receive gel and 35 to receive a pessary. Median scores for satisfaction of
      the induction process were the same for both methods; however, satisfaction with
      the labour was increased with those who had been randomised to the pessary group
      (median pessary=5, gel=4). There may be a marginal improvement in patient
      satisfaction when a slow-release intravaginal prostaglandin E2 pessary is used
      for the induction of labour.

PMID- 12521851
TI  - Histological chorioamnionitis in relation to clinical presentation at 14-40 weeks
      of gestation.
AB  - This study examines the prevalence of histological inflammation of the fetal
      membranes according to gestational age and mode of clinical presentation in a
      series of 179 consecutive placentas evaluated in a single centre. The frequency
      of histological inflammation between clinical groups was compared and relation
      between the prevalence of inflammation and gestational age examined using
      regression analysis. One hundred and seventy-nine placentas were examined.
      Histological inflammation was present in 65 (38%) cases including 37/52 (71%)
      pregnancies presenting with spontaneous preterm labour and delivery (PTL), 23/36
      (64%) with preterm prelabour rupture of membranes (PPROM), 1/20 (5%) with vaginal
      bleeding but no contractions (PVB), 1/13 (8%) with intrauterine death but no
      labour (IUD), 1/28 (4%) with iatrogenic delivery, 0/4 with termination of
      pregnancy and 2/20 (10%) delivering spontaneously at term. The prevalence of
      histological inflammation was significantly higher in those with PTL or PPROM
      compared to the other groups (P<0.0001). The frequency of histological
      inflammation was associated with gestational age (F=57.2, P<0.0001, R=0.91), with
      a peak prevalence (>90%) at 20-24 weeks' gestation.

PMID- 12521852
TI  - The influence of maternal age on pregnancy outcome in patients with early onset,
      severe pre-eclampsia.
AB  - Pregnancy outcomes of women in three age categories, < or = 19, 20-34 and > or =
      35 years, who underwent expectant management of early onset, severe pre-eclampsia
      were evaluated. This formed part of a prospective study involving 340 selected
      women from April 1992 to March 1997. Frequent monitoring of maternal and fetal
      status in a high-care obstetric ward was performed. Main outcome measures were
      major maternal complications, prolongation of gestation and perinatal outcome.
      Pregnancy was prolonged by a comparable number (10, 9 and 12) of days in the
      groups. Placental abruption was the most frequent major maternal complication,
      occurring more often in the youngest group (P=0.04). Women in this group also had
      the highest perinatal mortality and more often required anti-hypertensive
      medication at discharge (P<0.001). Younger women (< or = 19 years) appear to be
      at higher risk for maternal and perinatal complications.

PMID- 12521853
TI  - Soluble transferrin receptors in anaemia of pregnancy.
AB  - Anaemia is one of the most common disorders in pregnancy. The most common cause
      is iron deficiency. Iron deficiency anaemia is relatively easy to diagnose using
      a serum ferritin of <15 ng/ml. However, because ferritin is an acute phase
      reactant, the diagnosis of iron deficiency anaemia in hospitalised or ill
      patients may be difficult, since serum ferritin may be normal or raised, even in
      the face of iron deficiency. Soluble transferrin receptor assay (STfR) may be
      useful in these situations because it reflects the degree of iron requirement in
      relation to supply, and it is not an acute phase reactant. This study was
      undertaken to detect subclinical anaemia in pregnant women and to correlate STfR
      assay with the current diagnostic tests for iron deficiency anaemia. One hundred
      and fifty-three consenting pregnant women seen at the antenatal clinic at King
      Edward VIII Hospital (KEH) were recruited. Women on haemantinics, who had renal
      failure, haemoglinopathy and blood transfusion in the past 3 months, were
      excluded. An ELISA technique was used for the assay of STfR while standard
      methodology was used for the other biochemical and haematological assays (FBC,
      urea, creatinine, c reactive protein and iron studies). One hundred and fifty
      subjects were included in the final analysis. Seventy-two (48%) had varying
      degrees of iron deficiency anaemia. In 70% (105) of the samples analysed, serum
      ferritin and STfR agreed on the presence/absence of iron deficiency anaemia. STfR
      and S:F were 75% and 86% sensitive; 63% and 82% specific, respectively. The
      calculated positive and negative predictive values are: STfR 64% and 75%; S:F 84%
      and 87%; Hb 58% and 57%; mean corpuscular volume 91% and 55%, respectively.
      Ferritin remains the gold standard for the diagnosis of iron deficiency anaemia.
      However, because ferritin is an acute phase reactant, soluble transferrin
      receptor assay may be a better test in ill and hospitalised patients where
      ferritin may be normal or elevated, despite iron deficiency.

PMID- 12521854
TI  - Analysis of 44,279 blood glucose estimations in relation to outcomes in 80
      pregnant diabetic women.
AB  - A retrospective study was conducted to assess glycaemic control in relation to
      pregnancy outcomes in pre-existing and gestational diabetics. Computerised blood
      glucose records from 47 pre-existing diabetic patients and 33 gestational
      diabetics were collected prospectively and then analysed retrospectively in
      relation to pregnancy outcomes. There were two spontaneous miscarriages from the
      pre-existing diabetic cohort. A total of 44,279 individual blood glucose
      estimations were made. The mean fasting glucose for pre-existing diabetic
      patients fell significantly throughout pregnancy, being 7.7+/-2.1, 7.2+/-3.1 and
      6.5+/-2.4 mmol/l, respectively, for trimesters 1,2 and 3 (P<0.01). The mean post
      prandial glucose for each trimester were 8.9+/-2.0, 8.6+/-1.6 and 8.2+/-1.2
      mmol/l (P<0.01). The HbAlc for pre-existing diabetic patients for each trimester
      was 7.5+/-1.4%, 6.1+/-1.0% and 5.9+/-0.7%, respectively. Gestational diabetic
      patients had a mean fasting glucose of 5.6+/-1.5 mmol/l and a mean post-prandial
      glucose of 8.0+/-2.1 mmol/l during trimester 3. Home glucose monitoring
      correlated reasonably well with first trimester HbA1c (r2=0.43, P<0.001), but
      this relationship became less valid as pregnancy progressed. The mean gestation
      at delivery was 37 weeks, although 30% of women were delivered between 34 and 37
      weeks and 8% delivered before 34 weeks. Labour was induced in 49% of patients and
      the overall caesarean section rate was 58%. The mean birth weight for pre
      existing diabetic patients was 3479 g (1410-5000 g) and for women with
      gestational diabetes was 3605 g (1890-5920 g). For pre-existing diabetic patients
      HbA1c did not correlate with birth weight; however, home blood glucose data from
      trimester 2 did correlate (r2=0.15, P <0.005) and there appeared to be stronger
      relationship with trimester 3 data (r2=0.24, P <0.005). There was no association
      between trimester 3 glucose data and birth weight in the gestational cohort. The
      babies born to pre-existing diabetic mothers had a high incidence of admission to
      a neonatal unit and over 50% of the babies had proven hypoglycaemia. Our present
      computerised system for home blood glucose monitoring has shown that for pre
      existing diabetes patients but not gestational diabetic patients, glycaemic
      control in the second and third trimester influences birth weight. The current
      degree of glycaemic control in the mothers did not prevent a high rate of
      neonatal hypoglycaemia.

PMID- 12521855
TI  - Can cardiotocography prior to induction of labour predict obstetric intervention?
      A pilot study.
AB  - We set out to study the value of cardiotocography (CTG) performed before
      induction of labour for prolonged pregnancy in predicting obstetric intervention.
      This was a prospective observational study, based in a district general hospital.
      We studied 100 consecutive patients who underwent induction of labour for
      prolonged pregnancy. Cardiotocographs (CTGs) were performed before induction of
      labour on the tenth day after the estimated date of confinement (290 days). The
      CTGs were then reviewed without knowledge of the outcome of the induction of
      labour. Obstetric outcomes were then compared. The main outcome measures were the
      intrapartum presence or absence of meconium stained liquor and the necessity for
      obstetric intervention. Ninety per cent of CTGs were normal. There was no
      difference found between the two groups for operative delivery or the presence of
      meconium liquor. Caesarean section was more likely in the group with an abnormal
      CTG before induction of labour, but the possibility of this being due to chance
      is high in this study. There was one case of undiagnosed growth restriction in
      the abnormal CTG group. These results may be due to a true lack of difference in
      obstetric intervention between women with normal or abnormal CTGs prior to
      induction of labour or more probably an inability to detect a difference in our
      small study. These baseline data allow the calculations necessary for a more
      substantive trial.

PMID- 12521856
TI  - Outcome of prolonged pregnancy revisited in a Nigerian tertiary centre.
AB  - The study was conducted to evaluate whether routine induction of labour at 41-42
      weeks of gestation has an increased risk for operative delivery, maternal or
      fetal complication compared with spontaneously initiated labour of similar
      gestation. A case-control study design was used; main outcome measures were
      caesarean section rate, instrumental delivery and fetal outcome. There was no
      significant difference in caesarean section rates 36(18.0%) in the induction
      group, compared with 28(13.8%) in parturient spontaneously initiating labour
      [P=0.24 odds ratio 95% CI 1.37 (0.78:2.43)]. Instrumental interventions were
      comparable in the two groups (5.5% and 4.0%). A subgroup analysis of nulliparous
      women was also not statistically different. Other than higher rates of admission
      into the neonatal unit in the induction group, fetal outcomes were similar. In
      conclusion, a routine induction of labour for prolonged pregnancy is safe, having
      no significant increase in caesarean section or fetal complications. The policy
      is advocated especially in developing countries, in view of the uncertainty of
      further prolongation of pregnancy beyond 42 completed weeks.

PMID- 12521857
TI  - Down syndrome in the Czech Republic during 1961-1997: prevalence, prenatal
      diagnosis and maternal-age-specific rates.
AB  - Data from a population-based register of congenital anomalies in the Czech
      Republic (total number of 5,319,002 births from the period under the study and
      4933 Down syndrome cases) were used. Mean incidence of Down syndrome in births
      during the total period was 7.91/10,000 live births, the total incidence with the
      inclusion of prenatally diagnosed cases was 9.47/10,000 live births. The ratio of
      prenatally diagnosed cases out of the total number of Down syndrome cases
      increased in the period 1980-1997 from 20% to 60% in the whole population. The
      age distribution among mothers with Down syndrome babies shows a significantly
      increased risk for a maternal age of 34 years and over. The results indicate the
      important role of prenatal diagnosis in the change of incidence of Down syndrome
      at birth. Maternal age-specific rates must be used as basic data for improved
      calculation of individual risk in screening for Down syndrome in a population.

PMID- 12521858
TI  - Induced abortion and prematurity in a subsequent pregnancy: a study from
      Shanghai.
AB  - To evaluate the impact of a first trimester induced abortion on the risks of low
      birth weight (LBW) and preterm birth in a subsequent pregnancy we conducted a
      pregnancy-based cohort study in Shanghai, China with recruitment from 15 general
      hospitals (or maternity and infant health institutes) from November 1993 to March
      1998. Pregnant women with a history of induced abortion entered the abortion
      cohort and a reference cohort was established among women without such a history.
      All the subjects were enrolled before 64 days of gestation and interviewed five
      times until 42 days after delivery. Only singleton live births were analysed in
      this study. A total of 2953 pregnant women were enrolled and 2707 gave birth to
      live singletons. The overall incidence of LBW was 1.7%, 2.0% in the abortion
      cohort and 1.4% in the reference cohort. After controlling the potential
      confounders using logistic regression, the adjusted odds ratios were 1.7 (95% CI:
      0.8-3.3) for LBW, 2.0 (95% CI: 0.9-4.7) for term LBW and 1.0 (95% CI: 0.6-1.5)
      for preterm birth, following an induced abortion pregnancy. Birth weight in the
      abortion cohort was 38.5 g higher than that of the reference cohort after
      adjustment for calendar year at recruitment, couples' occupation, education, age,
      infant sex, maternal body mass index at recruitment, contraceptive use and
      gestation age. Previous first trimester induced abortion did not significantly
      increase the risk of LBW or preterm birth. The study was performed in a low-risk
      population and results may not be applicable to other settings.

PMID- 12521859
TI  - Normal fetal growth pattern in a Nigerian population.
AB  - The objective of this study was to establish normal reference range values for
      gestational age-specific fetal weights for normal pregnancies in our population.
      A longitudinal prospective assessment of fetal weight in healthy pregnant women
      was carried out. The subjects were recruited at 20 or 22 weeks' gestation and
      concluded at 40 or 42 weeks' respectively. The numerical data were analysed on an
      IBM personal systems 2 computer with statistical and graphical packages. From a
      mean of 407.27 g at 20 week gestation, the fetal weight progressively increased
      to 3630.00 g at 42 weeks' gestation. There were two growth spurs; 2830 weeks' and
      3436 weeks' gestation, respectively. Gestational age-specific reference range
      values of fetal weight has been derived for our population. The 5th and 95th
      centiles should be taken as the lower and upper limits of normal, respectively.

PMID- 12521860
TI  - Outcome of outpatient micro-hysteroscopy performed for abnormal bleeding while on
      hormone replacement therapy.
AB  - This retrospective observational study was carried out in a large district
      general hospital to review the outcome of outpatient micro-hysteroscopy performed
      on women with abnormal bleeding while on hormone replacement therapy. All women
      referred to the outpatient hysteroscopy unit with abnormal bleeding while on
      hormone replacement therapy between November 1994 and August 1998 had
      hysteroscopy performed using a 1.2 mm semi-rigid hysteroscope with a 2.5 mm
      sheath. Hysteroscopy was performed on 190 women. Ninety-two women (48.4%) had a
      normal uterine cavity, 38 (20%) had an atrophic endometrium, 52 (27.4%) were
      found to have endometrial polyps, seven (3.7%) had suspicious endometrium
      (histology showed two adenocarcinomas and three hyperplasias) and one patient
      (0.5%) had a submucous fibroid. Histological evaluation showed 145 (76.32%)
      specimens were benign, 37 (19.47%) specimens either contained no tissue or
      insufficient tissue for diagnosis, five (2.63%) showed hyperplasia and three
      (1.58%) were adenocarcinoma. Two hyperplasias and one focal adenocarcinoma were
      diagnosed in endometrial polyps. Nearly half of the women who had a hysteroscopy
      for abnormal bleeding while on hormone replacement therapy had a normal
      endometrial cavity. Almost one-third had endometrial pathology, of which the
      majority were endometrial polyps. The incidence of endometrial carcinoma was low.
      No abnormality was missed on hysteroscopy, but histology was normal in two
      patients with hysteroscopically suspicious endometrium.

PMID- 12521861
TI  - Mid-trimester termination of pregnancy by dilatation and evacuation.
AB  - The object of this study was to evaluate the feasibility and safety of Dilatation
      and Evacuation (D&E) as a method of termination of pregnancy in the second
      trimester. We conducted a retrospective analysis of 61 cases. The mean age of
      women was 25.6 years (range 1545) and the majority of terminations were performed
      for social reasons. Twelve women (20%) had at least one previous termination of
      pregnancy. The median gestational age was 16 weeks (range 1322). Except for three
      multiparous women, they all had Cervagem vaginal pessaries preoperatively and the
      mean operative time was 26.6 minutes. Most of the operations were performed under
      ultrasound guidance, but there was no increased risk of complications in the rest
      of the group. One multiparous woman suffered uterine perforation and severe
      haemorrhage, for which she underwent hysterectomy. One in four women tested
      positive for chlamydia infection. Evacuation of retained products of conception
      (ERPC) was required in four cases. No postoperative analgesia was required in 43%
      of women and most of the rest required only mild non-opiate analgesia. Except for
      two women, all were discharged from the hospital either on the same or the day
      after the operation. This retrospective study shows that surgical evacuation in
      the second trimester of pregnancy is a quick and well tolerated method of
      termination, although there is a risk of perforation and hysterectomy.

PMID- 12521862
TI  - Medical care use among women before and after sexual assault: a population study.
AB  - We set out to compare medical care utilisation patterns between women who were
      sexually assaulted and women who were not sexually assaulted in the year before
      and the year after the assault. Cases studied were 690 females aged 15 and over
      who had undergone a forensic evidence examination for sexual assault between
      April 1996 and March 1997 and the same number of female age-matched controls.
      This was a population-based, matched case-control study using administrative
      databases of medical encounters (only physician services). Outcomes included
      physician visits by physician specialty; clinic and hospital diagnoses and
      hospital discharges. Of the cases, 38.4% were aged 1519; 21.4% aged 2024; and
      40.2% aged 25 or older. Before and after the sexual assault, cases were more
      frequent users of medical services than controls. Cases were seen more often,
      received more medical services and were more likely to be hospitalised than
      controls in both time periods. Cases were also more likely to be diagnosed with a
      vast range of physical and psychological problems during the period of study. The
      persistence of mental and physical health problems before and after a forensic
      examination for sexual assault presents a challenge. Of paramount concern are
      issues concerning informed consent to undergo the examination. Collection and
      documentation of evidence may be important for victims with severe mental illness
      who may have more difficulty testifying in court. Our study suggests the need for
      future research examining the reasons why women do not undergo the examination
      both in terms of whether it is offered and declined or not offered to them.

PMID- 12521863
TI  - Knowledge, awareness and perception of sexually transmitted diseases (STDs) among
      antenatal patients at Nnewi, Nigeria.
AB  - This study investigates STD knowledge, awareness and perception among antenatal
      patients at a Nigerian teaching hospital. There was general awareness of the
      common STDs, such as gonorrhoea, 95.5% (n=127) and syphilis 66.92% (n=89), while
      the least awareness was recorded in chlamydial diseases, 6% (n=8). HIV/AIDS
      recorded the highest awareness, 96.2% (n=128). There knowledge of causes and
      treatment was remarkably poor. Only 58.6% (n=78) could recognise bacteria as
      causing STD. Surprisingly more than half, 72.2% (n=96) still believed that remedy
      could be obtained from prayer houses, herbs and other non-scientific means. The
      most common source of information was through media houses: radio 72.9% (n=97),
      television 64.7% (n=86). Preventive awareness was high, more than half believing
      that STD is preventable either by abstinence, barrier contraception or by mutual
      fidelity. Superstitious beliefs, greater influence of traditional medical
      practices and poverty are some of the numerous problems the few existing STD
      clinics face in the developing countries. Efforts should be geared towards
      establishing standard STD clinics and appropriate information disseminating
      organs. A situation where the herbalists and traditional medical personnel
      capture the mostly ignorant populace through unrestricted access to the media
      houses, as currently practiced in Nigeria, should be checked.

PMID- 12521864
TI  - Vasectomy in developing countries.
AB  - Vasectomy is an acceptable technique of sterilisation in affluent societies;
      however, cultural barriers exist in most parts of Africa. The object of this
      study was to establish the prevalence of vasectomies at King George V Hospital
      (KGH), Durban, over a 3-year period, to determine attitudes towards vasectomy,
      and to identify ways of improving its acceptability. This was a retrospective
      study. Clinical details of case files were analysed and interviews of clients who
      had vasectomy were conducted telephonically or through home visits. A total of
      308 (88.3%) clients were contacted. The mean age at vasectomy was 35 years (range
      15-51 years). The majority, 50.3%, were Indians; 21% whites, 15.6% coloured and
      12.3% were Africans; 290 of the men were married with a mean duration of marriage
      of 10.3 years (3-25 years). Ninety-four per cent were in a monogamous
      relationship and all remained married to date. Sixty-four per cent had above
      matriculation educational status. Most of the patients became aware of vasectomy
      through family planning clinics or health personnel; only 4.9% received
      information through the media. Fifty-three per cent (n=164) of couples had
      problems with previously used contraception prior to decision for vasectomy. The
      complication rate was 6.5% while 1% regretted having had the procedure. Only two
      men (0.7%) desired reversal. On direct questioning, sexual activity remained
      unchanged in 95.1%, and actually improved in 3.2% of the men following vasectomy.
      Most believed that there is not enough information on vasectomy available,
      especially through the media, and that with appropriate counselling vasectomy is
      a safe permanent contraception that should be actively promoted.

PMID- 12521865
TI  - Sexual behaviour and contraceptive use among secondary school adolescents in
      Benin City, Nigeria.
AB  - This study was designed to examine sexual behaviour and contraceptive use among
      in-school adolescents in Benin City, Nigeria. A random sample of 431 females and
      440 males aged 14-21 years from secondary schools in Benin City, Nigeria, were
      interviewed using a structured pretested questionnaire. The results show that 23%
      of the females and 40% of males had initiated sexual intercourse. Among those who
      had done so, the median age at first sexual debut was 16.8 years for girls and
      15.4 years for boys. Only 22.2% of females and 23.9% of males used contraception
      at first sexual intercourse. Use of contraception among sexually active
      adolescents at last sexual debut declined to 18.6% for females and 22.2% for
      males. Forty-two per cent of sexually active adolescents engaged in high-risk
      sexual behaviour. In conclusion, the low prevalence of effective contraceptive
      use and time-related decline in usage indicate a need for greater emphasis on sex
      education aimed at adolescents in Nigeria.

PMID- 12521867
TI  - Obstetric Case Reports.

PMID- 12521866
TI  - Sexual behaviour of infertile Nigerian women.
AB  - The objective of this study is to examine the sexual behaviour of infertile women
      in Ile-Ife, Nigeria and to elucidate to what extent women seeking treatment for
      secondary infertility are at risk of sexually transmitted diseases. In a 1-year
      study period, 236 secondarily infertile women (cases) and 472 pregnant women
      (controls) were interviewed using detailed open-ended questionnaires. Infertile
      women were at a significant risk of having multiple sexual partners OR 3.80 (1.97
      7.32), reproductive tract infections OR 8.52 (5.08-14.37), early age at first
      sexual intercourse OR 19.13 (92.45-29.47) and poor condom use OR 4.50 (2.01-9.31)
      compared to controls (pregnant women). The paper discusses the reasons for the
      above observations and made recommendations aimed at reducing the infections
      related infertility in this subregion.

PMID- 12521868
TI  - Gynaecology Case Reports.

PMID- 12521869
TI  - Ethical guidelines in the prevention of iatrogenic multiple pregnancy.

PMID- 12521871
TI  - Conference Diary.

PMID- 12521872
TI  - The new MRCOG Objective Structured Clinical Examination--the examiners
      evaluation.
AB  - Following criticism of the clinical and viva sections of the previous Part II
      MRCOG examination, the Royal College of Obstetricians and Gynaecologists (RCOG)
      introduced an objective structured clinical examination (OSCE) in November 1998.
      This replaced the previous clinical and viva voce sections and was designed to
      allow a fairer, more reliable and more reproducible method of candidate
      assessment. We set out to document the examiners' response to the first MRCOG
      Part II OSCE and to evaluate their assessment of the new format compared to the
      old. We conducted a retrospective survey of all 76 examiners involved in the new
      style OSCE format. A questionnaire was posted to all examiners and a further
      questionnaire was sent out to the initial non-responders. The questionnaire was
      designed to determine whether or not examiners had examined for the MRCOG Part II
      before and if so to evaluate their assessment of the new format compared to the
      old. All examiners were then asked to score each OSCE station. The score
      represented the examiners view of the station's ability to assess the clinical
      skill that it had been designed to test. Median scores were determined for each
      question. A space was provided for general comments. Seventy-two of 76 examiners
      returned their questionnaires (two were excluded), a 95% response rate. Seventy
      eight per cent of examiners had examined before and considered the standard of
      the exam to be comparable with the old format, a median score of 3 (range 1-5).
      In addition they found the OSCEs to be a much fairer method of candidate
      assessment, median score 4 (range 1-5). The majority of median scores relating to
      OSCE stations were 4 and 5, suggesting that examiners felt the stations assessed
      the candidates, clinical skills adequately. Sixty-eight of 70 (97%) examiners
      felt the new format should remain and 57 of 70 (81%) felt it would be suitable
      for adoption by other specialities. The first MRCOG Part II OSCE was generally
      well received by the examiners and was an organisational success. Our survey of
      examiners revealed that the new format was considered to be of the same standard
      as previous examinations, but that the new format was perceived to be much
      fairer. The majority of OSCE stations adequately tested the clinical skills they
      were designed to assess. With ongoing evaluation and development it is
      anticipated that this proportion will increase. The success of the new format
      suggests that OSCEs will remain as the final clinical examination for
      postgraduate obstetrics and gynaecology.

PMID- 12521873
TI  - Management of obstetric emergencies and trauma (MOET): regional questionnaire
      survey of obstetric practice among career obstetricians in the United Kingdom.
AB  - Across specialties in the UK concern exists that the shortened training time,
      combined with the restriction on hours of work, will result in trainees being
      short of the necessary depth and breadth of experience for independent practice
      at the end of their defined training period. In terms of risk management, it is
      recognised that high reliability organisations anticipate the worst and equip
      themselves to deal with it at all levels in the organisation. Alternative methods
      of assessment and training need to be utilised, including models and scenario
      teaching. While it is important for clinicians to learn common skills well before
      practising on the labour ward, it is correspondingly more important that rare
      complications be rehearsed with models. In the UK, the MOET (Managing Obstetric
      Emergencies and Trauma) course has been developed to allow specialist
      obstetricians to learn, or revise, how to undertake procedures on models, and
      then to have their skills tested in scenarios. This survey aimed to ascertain the
      views of career obstetricians in terms of their ability to respond to some of the
      course scenarios and how frequently the rarest procedures have been undertaken. A
      one-page questionnaire with 15 questions, based on clinical scenarios taught on
      the MOET (Managing Obstetric Emergencies and Trauma), course was sent to all
      career obstetricians in the West Midlands region. Participants were asked to
      indicate whether they thought a particular management was 'good practice', 'bad
      practice' or 'good practice but would prefer a caesarean section' and to indicate
      the number of such procedures they had undertaken in their obstetric career. The
      response rate was 40% (97/243). There was a broad spectrum in obstetric views
      about 'good' and 'bad' practice. Overall the respondents agreed with the
      literature in terms of practices that are regarded as 'good' and 'bad'. A large
      proportion of respondents, however, would rather undertake a caesarean section
      than carry out a 'good' practice. Twenty-six obstetricians had experience in the
      rare obstetric procedures. Of these, 16 (66%) had worked outside the UK, either
      in the Middle East, South East Asia, Africa or the Caribbean. This survey
      highlights the need for training courses to teach and revise operative
      procedures.

PMID- 12521874
TI  - Information derived from hospital coded data is inaccurate: the Birmingham
      Women's Hospital experience.
AB  - We tested the accuracy of coded hospital information on the Patient
      Administration System (PAS), a major component of the Hospital Information
      Support System (HISS). This is the main electronic database used for healthcare
      research, audit, and planning in National Health Service hospitals in the UK. The
      accuracy of electronic records of diagnoses, interventions and diagnosis
      intervention pairs was low. (Kappa agreement statistics [k] were 0.39, 0.30, and
      0.21 respectively). A major source of error arose because the databases of
      maternities and surgical operations were not seamlessly linked to the PAS.

PMID- 12521875
TI  - The relationships between neonatal encephalopathy and cerebral palsy: a cohort
      study.
AB  - There is a high risk of cerebral palsy (CP) following neonatal encephalopathy
      (NE) with fits, often attributed to intrapartum asphyxia. The evidence for the
      association is inconclusive and antepartum factors offer an alternative
      explanation. A cohort study was carried out to assess the evidence for and
      against hypoxic ischaemic injury as the cause of NE-associated CP in term
      infants. A total of 57 159 consecutive births were enrolled. There were 150 cases
      with NE, of whom 92 had at least one fit and 58 had no fits. The incidence of all
      NE was 2.62 per 1000 births and of NE with fits was 1.61 per 1000 births. Infants
      with NE were followed-up to identify those with cerebral palsy. There were 13
      cases of four-limb cerebral palsy and three with hemiplegia among the survivors.
      In 12 of the 13 cases of four-limb CP, a combination of low Apgar scores, an
      early onset acute evolving encephalopathy, acidosis, renal dysfunction and the
      absence of antepartum factors suggested an acute intrapartum event as the
      immediate cause of the NE. An obstetric event likely to cause acute hypoxic
      injury was identified in four of the 12 cases. The clinical picture was similar
      in the four with and the eight without a specific obstetric event. The pathway
      leading to NE-associated CP remains unexplained, but intrapartum events appear to
      play a major role in most cases.

PMID- 12521876
TI  - Peripartum hysterectomy in the 1990s: any new lessons?
AB  - We aimed to identify the risk factors and subsequent maternal and perinatal
      outcome associated with the procedure of peripartum hysterectomy. This was a
      retrospective case review carried out at the National Maternity Hospital, Dublin,
      of all patients who underwent a peripartum hysterectomy from January 1990 to
      December 1999. Seventeen cases were performed during the study period from a
      total of 64 563 deliveries (0.03%). Mean maternal age was 34 years (21-43). There
      were no nulliparous patients. Eight patients had previous vaginal deliveries. The
      other nine had a history of previous caesarean section, four of whom had two or
      more caesarean sections. The indications for the hysterectomy were placenta
      praevia (5), secondary postpartum haemorrhage (3), abruptio placentae (3), atonic
      postpartum haemorrhage (2), placenta accreta (2), traumatic postpartum
      haemorrhage (1) and broad ligament haematoma (1). All patients received blood
      transfusions, 74% receiving more than 10 units. There were no maternal deaths.
      There were two neonatal deaths secondary to placental abruption (perinatal
      mortality rate 118/1000). In conclusion, there was no maternal death in this
      study but the associated maternal morbidity and perinatal mortality was high.
      More than half the cases were associated with previous caesarean section. The
      caesarean section rate is increasing worldwide for many reasons, including recent
      emphasis on maternal request. We recommend that caesarean section be performed
      only for valid clinical indications, which should help to reduce the problems
      associated with peripartum hysterectomy.

PMID- 12521877
TI  - A survey of the influence of patients' choice on the increase in the caesarean
      section rate.
AB  - The caesarean section rate in the Royal Gwent Hospital has, as in the rest of the
      UK, risen significantly over the last 10 years. A commonly proposed reason for
      this increase is that women themselves are now more likely to request an elective
      caesarean section, when there is little or no medical indication. The aim of this
      survey, carried out prospectively, was to find out whether patients' requests for
      caesarean section are contributing significantly to the rise in the section rate,
      by attempting to actually quantify the influence of patients' choice on the
      decision to perform a caesarean section. The results showed that it is possible
      to quantify this influence, and that maternal request does play a major role in
      the decision-making process.

PMID- 12521878
TI  - Elective caesarean section--the patient's choice?
AB  - It has traditionally been considered inappropriate for women to have an elective
      caesarean section on request in an uncomplicated pregnancy. In previous studies,
      female obstetricians and midwives have been questioned on their preferred mode of
      delivery. This study asked 344 women attending a routine antenatal booking clinic
      what mode of delivery they would prefer in an uncomplicated pregnancy and why. Of
      the women questioned, 14.5% opted for an elective caesarean section at 39 weeks'
      gestation. The main reasons being to avoid maternal trauma, to avoid a prolonged
      labour and for fetal wellbeing. A caesarean section may have some potential
      benefits over a vaginal delivery and it is hard to refuse a well-informed woman
      an elective caesarean section on request, even if it results in a further rise in
      the rate of caesarean section.

PMID- 12521879
TI  - Effect of postpartum anxiety on the colostral milk beta-endorphin concentrations
      of breastfeeding mothers.
AB  - Peripartal maternal apprehension and anxiety are associated with abnormal labour,
      dystocia and higher rates of fetal and maternal morbidity. Since colostral beta
      endorphin (beta-EP) concentrations are twofold higher than circulating levels, we
      hypothesised that substantial maternal emotional distress in puerperium might
      induce consistent changes in colostral beta endorphin galactopoiesis. To test
      this hypothesis, we assessed the effects of postpartum maternal anxiety (State
      Trait Anxiety Inventory-Y form, Spielberger CD, Palo Alto, CA, USA, 1983) on
      colostral milk beta-EP levels (beta-endorphin 125I RIA, INCSTAR Corporation
      Stillwater, Minnesota, USA) in a population of healthy lactating mothers, on the
      fourth postpartum discharge day, 14 after at term vaginal delivery, 14 after
      premature (> or = 34 <37 gestational weeks) vaginal delivery, and 14 after
      elective cesarean section. The colostral milk beta-EP concentrations of mothers
      who vaginally delivered at term or prematurely were significantly higher on the
      fourth postpartum day (6.0+/-0.5 and 6.6+/-0.7 vs. 4.3+/-0.4 pmol/l,
      respectively; P <0.05) than colostral levels of mothers who underwent caesarean
      section. At the same time, while trait anxiety levels (T, age corrected values)
      were unaffected by route and mode of delivery, in mothers presenting increased
      colostral milk beta-EP galactopoiesis after vaginal delivery there was a
      statistically significant negative correlation (r-0.40; P <0.03) between
      colostral milk beta-EP concentrations and trait anxiety levels. These data
      indicate that the labour pain and the vaginal delivery process play a central
      role in increasing colostral opioid availability for the breastfed neonate;
      peripartal maternal anxiety is a negative psychobiological determinant in opioid
      galactopoiesis, and possibly in the postnatal development of several related
      biological functions of growing infants.

PMID- 12521880
TI  - Platelet angiotensin II binding may be a useful prognostic indicator for the
      development of pre-eclampsia in women with pregnancy-induced hypertension:
      preliminary communication.
AB  - This was a preliminary investigation to assess the value of platelet angiotensin
      II binding as a prognostic indicator for subsequent pre-eclampsia in women
      admitted with non-proteinuric pregnancy-induced hypertension. Platelet
      angiotensin II binding was measured in 26 women at the onset of their symptoms.
      All were primparous, had singleton pregnancies, were normotensive at booking and
      had an unremarkable medical history. The blood pressure of seven women resolved
      and returned to normal; 11 women remained stable throughout the remainder of
      their pregnancy, their blood pressure remained elevated but they did not develop
      significant proteinuria. Eight women developed pre-eclampsia. Platelet
      angiotensin II binding in the pre-eclamptic group was significantly higher
      compared to those who remained stable (P = 0.042) or those whose condition
      improved (P = 0.021). We conclude that angiotensin II binding measured at the
      time of admission to hospital for non-proteinuric pregnancy-induced hypertension
      may have a role in predicting the onset of pre-eclampsia or eclampsia.

PMID- 12521881
TI  - Audit on the use of thromboprophylaxis during caesarean section.
AB  - Thromboembolic disease is still a main cause of maternal morbidity and mortality.
      In 1995 the RCOG working party on prophylaxis against thromboembolism has
      suggested that patients undergoing caesarean section should have a risk
      assessment and be given heparin prophylaxis if deemed to be high risk. In
      Stepping Hill Hospital this was audited. The outcome was that 0% of emergency
      caesarean sections, and only 25% of elective caesarean sections who were
      considered to be high risk had heparin prophylaxis. A structured risk assessment
      form was introduced for every patient undergoing caesarean section and the
      outcome was re-audited; 72.7% and 85.7% of emergency and elective caesarean
      sections, respectively,that were deemed high risk had adequate heparin
      thromboembolic prophylaxis. Filling in a risk assessment form before performing a
      caesarean section reminds and reinforces the need to consider thromboprophylaxis.
      A risk assessment form has been formally incorporated into all the maternity case
      records.

PMID- 12521882
TI  - Prevalence of asymptomatic bacteriuria among pregnant women in Benin City,
      Nigeria.
AB  - A semi-quantitative screening for asymptomatic bacteriuria was carried out in the
      first trimester of 500 consecutive pregnant women in Benin City. The purpose was
      to provide baseline data and rational therapy for asymptomatic bacteriuria in
      pregnant women. Of the 500 women screened, 433 clinical specimens showed
      significant bacteriuria, representing an incidence of 86.6%. Of this number, 38
      (7.4%) were of mixed bacterial colonies while 395 (91%) were of single bacterial
      colonies. Staphylococcus aureus (29.8%), Escherichia coli (29.1%) and Klebsiella
      pneumoniae (21.5%) were the most frequently isolated pathogens. The high
      incidence of asymptomatic bacteriuria in pregnancy correlated significantly (P <
      0.05) with the observed high proportion of pyuria. On average, sensitivity of the
      pathogens was ciprofloxacin 99.7%; ceftazidime 81.6%; co-trimoxazole 79.4%;
      augmentin 71.4%; nalidixic acid 61.7%; nitrofurantoin 61.%; gentamycin 56.9% and
      ampicillin 25.4%. S. aureus was most sensitive, while Proteus mirabilis was least
      sensitive among the pathogens. Rational therapy of asymptomatic bacteriuria in
      pregnant women may prevent associated risks such as pyelonephritis and pre
      eclampsia.

PMID- 12521883
TI  - Screening for trisomy 21: the significance of a positive second trimester serum
      screen in women screen negative after a nuchal translucency scan.
AB  - Screening of pregnancies for trisomy 21 is now an accepted part of antenatal
      care. Measurement of fetal nuchal translucency in the first trimester and
      analysis of maternal serum biochemistry in the second trimester are both
      established methods of screening. The performance characteristics of both tests
      in an unselected population are well described and the choice of test offered is
      usually determined by local policy and resources. We present data from a
      screening programme offering women with a low risk result from nuchal
      translucency measurement a second trimester serum screen. There were eight cases
      of trisomy 21 in the 2683 women screened, all of which presented with a high-risk
      nuchal screen result. Serum screening of 1057 women who screened negative by
      nuchal translucency gave 46 high-risk results, all of which were, therefore,
      false positive for trisomy 21. Second trimester biochemistry screening following
      a negative nuchal translucency screen did not increase the detection of trisomy
      21.

PMID- 12521884
TI  - Pregnancy outcome in women with prosthetic heart valves.
AB  - The pregnancy outcome of 59 pregnancies in 38 women with prosthetic heart valves,
      managed at a tertiary referral centre from 1989-98 were reviewed. Ten women
      underwent valve replacement during pregnancy. The main outcome measures were
      major maternal complications and perinatal outcome. The maternal mortality rate
      for pregnancies following valve replacement surgery was 6.1%, with a 21%
      pregnancy loss before viability and a perinatal loss of 8%. Major morbidity in
      this group was as follows: haemorrhage 29.8%, cardiac failure 12.8%,
      thromboembolism 8.5%, infective endocarditis 6.4% and valve thrombosis 4.3%. No
      maternal mortality occurred among those who underwent valve replacement during
      pregnancy but their perinatal loss was 25%. We conclude that although maternal
      mortality and morbidity rates in women with prosthetic heart valves who became
      pregnant were high, the perinatal outcome was good except for women who underwent
      valve replacement during pregnancy who experienced a high perinatal loss rate.

PMID- 12521885
TI  - Linear analysis of fetal magnetocardiogram recordings in normal pregnancies at
      various gestational ages.
AB  - In this study we investigated the fetal magnetocardiogram recordings (FMCG) in 64
      women, 21-30 years old, with single normal pregnancies and gestational ages 28-40
      weeks. Spectral analysis was used to quantify heart rate variability and to
      identify the maturation of the autonomic nervous system. According to our
      results, there was an increase of the ratio LF/HF of the power spectrum, which
      reflects the maturation of the autonomous nervous system and also an increase in
      heart rate variability in the course of pregnancies, which was statistically
      significant (ANOVA test, P < 0.0005) comparing the R-R intervals of the number of
      cases in the four groups of 28-30, 37-40, 31-33 and 37-40 weeks of gestation.
      This study highlights some of the advantages of FMCG as a novel, non-invasive
      technique for obtaining useful clinical information.

PMID- 12521887
TI  - The sex ratio of births associated with placenta praevia.

PMID- 12521886
TI  - Identifying gestational diabetes mellitus and the effect of different diagnostic
      criteria.

PMID- 12521888
TI  - The long-term success of abdominovaginal sling operations for genuine stress
      incontinence and a cystocoele--a questionnaire-based study.
AB  - Abdominovaginal sling surgery is performed in women with genuine stress
      incontinence. It is not usually a primary operation because of the higher
      morbidity compared to the colposuspension. Slings are indicated in incontinent
      women with previous failed surgery, urethral hypermobility, intrinsic sphincter
      weakness, significant anterior vaginal wall prolapse or those with restricted
      vaginal mobility. This study was undertaken to assess long-term patient perceived
      success of abdominovaginal sling surgery in women with genuine stress
      incontinence (GSI) in the presence of a cystocoele. The case notes were reviewed
      of all 37 women undergoing sling surgery for GSI in the presence of a significant
      cystocoele between 1988 and 1999. Patients were sent a questionnaire at a minimum
      follow-up of 12 months enquiring about urinary symptoms. The mean duration of
      follow-up was 49 months. Six weeks following surgery 33/37 (89%) were completely
      dry. Thirty-three women (89%) responded to the questionnaire. Of these 14/33
      (42%) were totally dry, 10/33 (30%) had insignificant leakage and 9/33 required
      regular protection. The mean visual analogue score of improvement in incontinence
      was 75.3 (+/-30.1). The operation was deemed successful in 24/33 (72%) women.
      Voiding difficulty was reported in 12% and recurrent prolapse occurred in 15%. Of
      the failures 8/9 reported urge incontinence and 4/9 stress incontinence.
      Frequency, urgency and urge incontinence were significantly more common in the
      women in whom the operation failed. This study demonstrates a 72% long-term
      success of abdominovaginal sling operations in women with GSI and a significant
      cystocoele. Development of DI accounted for most of the operative failures.

PMID- 12521889
TI  - The hysterectomy lottery.
AB  - We report a postal survey of consultant gynaecologists carried out to determine
      the pattern of current hysterectomy practice, to obtain views on indications and
      contraindications to vaginal hysterectomy, and to predict future practice. There
      was a 75% response rate. Approximately two-thirds of hysterectomies were
      performed abdominally, one-third vaginally and 3% laparoscopically by each
      gynaecologist, although there was significant variation between them. The most
      common factors limiting the use of vaginal hysterectomy were a lack of uterine
      prolapse, the presence of fibroids and the need for prophylactic oophorectomy. It
      was predicted that there would be a significant change in hysterectomy practice
      with the majority being performed vaginally but still with a large variation.
      Gynaecologists who currently perform laparoscopic hysterectomy have the highest
      vaginal hysterectomy rates and predict the greatest role for it in the future.
      The large variations in practice indicate that the route of surgery is more
      dependent on the clinical preference of the gynaecologist than the medical
      condition.

PMID- 12521890
TI  - Late termination for fetal abnormality: providing essential information for
      parents.
AB  - Termination of pregnancy for fetal abnormality in the second half of pregnancy is
      a distressing experience for parents who are often fearful of the process of
      termination. Some of this fear may be engendered by a lack of information, and
      staff caring for couples in this situation may not feel sufficiently sure of the
      likely course of late termination to answer their questions. There is little
      existing literature to provide guidance. We studied all late terminations for
      abnormality occurring in our unit over an 18-month period in order to provide
      parents and staff with appropriate information.

PMID- 12521891
TI  - Commencement and maintenance compliance of patients on hormone replacement
      therapy (HRT) following bilateral oophorectomy.
AB  - In a survey in 1989 Spector observed that 70% of women who had had bilateral
      oophorectomy had never received hormone replacement therapy. Ten years after his
      survey we decided to audit not only the number of women who started hormone
      replacement therapy following bilateral oophorectomy, but also to determine long
      term compliance, as this is vital if the full benefits of oestrogen replacement
      are to be obtained. We carried out a survey of 91 women age 45 years and below
      who had bilateral oophorectomy in a teaching hospital and who were under the care
      of GPs in 53 general practices in the north-east of England. Of these women,
      72.4% were prescribed oestrogen replacement therapy in hospital before discharge.
      However, within 2 months following bilateral oophorectomy, 97.4% of these women
      had commenced hormone replacement; 88.4% have maintained hormone replacement for
      5 years or more, 11.8% who had started hormone replacement had discontinued
      within 5 years and 2.6% have never been on hormone replacement therapy, despite
      the lack of any medical contraindication. This survey shows a marked improvement
      in the long-term compliance of women on hormone replacement following bilateral
      oophorectomy. Continuous education of medical staff and patients on the benefits
      of hormone replacement therapy, preoperative counseling of patients with the
      opportunity for them to choose the route of administration that best suits them,
      and regular review of patients on hormone replacement therapy may further enhance
      long-term compliance.

PMID- 12521892
TI  - Cold knife cone biopsy--a valid diagnostic tool and treatment option for lesions
      of the cervix.
AB  - We present a case series of cold knife cone biopsy with emphasis on validation of
      the technique for ongoing and future use. This involved: analysis of 100 cold
      knife cone biopsies performed between 1987 and 1997. Data were gathered relating
      to indications, technique, postoperative morbidity, histological findings and
      results of long-term follow-up. Mean age was 41.8 years, and mean parity 2. Smear
      abnormalities of moderate or severe dyskaryosis were present in 74% of cases, and
      glandular abnormalities in 8%. Colposcopic diagnosis of CIN II-III was made in
      55% of cases, and invasion suspected in 12%. The main indications for conisation
      were inability to visualise the entire squamocolumnar junction (64%), disparity
      in cytological and colposcopic findings (26%), and colposcopic suspicion of
      invasion (12%). Mean blood loss was 90 ml. One patient (1%) required hysterectomy
      and blood transfusion to control secondary haemorrhage. Postoperative infection
      occurred in 5%, and cervical stenosis in 3%. All specimens were adequate for
      histopathological evaluation, including the margin, CIN was histologically proven
      in 67% of specimens, microinvasion in 4%, adenocarcinoma in-situ in 3%, and
      invasion in 3%. During a mean follow-up of 4.5 years (range 1.5-11 years), cure
      rate after complete excision was 97% and after incomplete excision was 85% (P >
      0.05) Despite the advent of alternative methods of treatment, cold knife cone
      biopsy remains an acceptable option in the management of CIN and microinvasion of
      the cervix. There are valid indications for the technique. When properly
      performed, it gives accurate representation of the disease process, has low risk
      of complications and is curative in most cases.

PMID- 12521893
TI  - The influence of the sex of the general practitioner on referral to a vulval
      clinic.
AB  - Two hundred consecutive patients attending a dermatology vulval clinic in two
      hospitals were identified retrospectively. The sex and status of the referring
      doctor and the sex of the registered general practitioner was recorded. The
      length of symptoms prior to referral was determined. Female doctors referred 63%
      of women, despite only 38% being registered with a female general practitioner.
      Women referred by their own female general practitioners had a shorter mean
      duration of symptoms (3.4 years) than those registered with a male doctor but
      referred by a female (4.2 years). This study confirms that female doctors refer
      the majority of patients with vulval problems. Women registered with a female
      general practitioner tend to be referred earlier.

PMID- 12521894
TI  - Vulval punch biopsies: what is the experience of patients and do they alter
      management?
AB  - A questionnaire was used to assess the use of vulval punch biopsies with regard
      to patient acceptance, complications and relevance to management in patients
      attending the Oxford vulval clinic over a period of 1 year. All were satisfied
      with the reasons given for the biopsy. The majority (70%) found the injection of
      the local anaesthetic to be the most painful part of the procedure. Only minimal
      bleeding continued after the biopsy in a third of patients and stopped
      spontaneously within a few hours. None of the patients had secondary infection or
      chronic ulceration. The most common diagnosis confirmed by biopsy at the Oxford
      vulval clinic was lichen sclerosus (LS) and the mean age of patients was 63.6
      years. Although no malignancy was diagnosed in our patients, in view of potential
      for malignancy and the lack of significant side effects associated with the
      procedure, we would recommend that punch biopsies be performed if LS is
      suspected.

PMID- 12521895
TI  - Transvaginal ultrasound scan versus laparoscopy in the diagnosis of suspected
      ectopic pregnancy.
AB  - This is a prospective study comparing the performance of transvaginal ultrasound
      scan with laparoscopy as the last diagnostic tool in a clinically suspected
      ectopic pregnancy. Both diagnostic methods have the same sensitivity of 100%.
      Transvaginal ultrasound scan had a specificity of 73.7% and a positive predictive
      value of 89.8%. Laparoscopy had a specificity of 84.8% and a positive predictive
      value of 94.6%. The use of laparoscopy could avoid laparotomy in only 3.4% of
      patients. Since transvaginal ultrasound scan is easier, safer and cheaper than
      laparoscopy, more emphasis should be laid on its use in our environment than
      laparoscopy.

PMID- 12521896
TI  - Treatment of chronic anovulation resistant to clomiphene citrate (CC) by using
      gonadotrophin-releasing hormone agonist (GnRH-a) ovarian suppression followed by
      recombinant follicle-stimulating hormone (r-hFSH) treatment (Suprecur, Puregon).
AB  - We performed a prospective study to assess the effects of a starting dose of 50
      units of recombinant follicle stimulating hormone (Puregon) during gonadotrophin
      releasing hormone agonist therapy (Suprecur) on follicular development in
      patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). In a
      prospective clinical trial, 25 women with clomiphene citrate-resistant PCOS who
      wanted to become pregnant were treated by a low-dose step-up protocol of SC
      recombinant follicle stimulating hormone administration during gonadotrophin
      releasing hormone agonist therapy, monitored by transvaginal ultrasonography and
      retrospectively by serum endocrine assays taken at each monitoring visit.
      Cancellation of cycles, ovulation, rate and size of follicles growth, serum E2
      concentration and pregnancy were recorded. All patients exhibited a response: 22
      patients ovulated, of whom 10 conceived. Using the low-dose protocol during
      gonadotrophin-releasing hormone agonist therapy permitted induction of ovulation
      safely and successfully in patients with clomiphene citrate-resistant PCOS who
      were patients previously difficult to treat with the conventional ovulation
      induction protocol.

PMID- 12521897
TI  - Obstetric Case Reports.

PMID- 12521898
TI  - Gynaecology Case Reports.

PMID- 12521900
TI  - Conference Diary.

PMID- 12521902
TI  - Gestational nose.

PMID- 12521901
TI  - Current cerebrovascular neuroimaging modalities and their application to
      eclampsia.

PMID- 12521903
TI  - Renal function following pregnancy in renal transplant recipients.
AB  - We set out to analyse the effect of pregnancy and hypertension in renal
      transplant recipients and review serum creatinine levels as a marker of graft
      function, before, during and after pregnancy. The study was conducted at a major
      tertiary referral centre in London. This was a retrospective analysis of renal
      transplant patients who had achieved a successful pregnancy. During the period
      1967-1998, there have been 272 women of childbearing age with successful renal
      transplants functioning for over 1 year. Within this population there have been
      66 pregnancies in 41 patients resulting in 53 births. Among the pregnancies that
      progressed beyond 24 weeks, preterm delivery occurred in 32 (60.4%). The mean
      gestation was 35.7 (range 30-41), mean birth weight was 2365 grams (range 908
      3430 grams) with 47%of infants weighing <2500 grams. There were vaginal
      deliveries in 14 (26%), the rest delivered by caesarean section. Patients that
      developed hypertension in late pregnancy tended to have higher pre-pregnancy
      creatinine levels and a deterioration of graft function postpartum. Serum
      creatinine levels greater than 130 micromol/l before pregnancy predict
      deteriorating renal function postpartum. Kaplan-Meier life survival analysis
      showed that the risk of subsequent graft loss is associated with increased serum
      creatinine levels (130-180 micromol/l) before pregnancy. Pregnancy figures in our
      unit are favourable compared to those reported in the literature. Poor pre
      pregnancy renal function (creatinine 130-180 micromol/l) and previous
      hypertension is associated with a significant risk of graft failure. Creatinine
      levels currently deemed as being acceptable during the pregnancy of renal
      transplant recipients may need to be reappraised.

PMID- 12521904
TI  - Varicella zoster during pregnancy: a strategy for prevention.
AB  - This is a retrospective case-control study to calculate the incidence of
      varicella zoster (VZ) in pregnancy, to know why the incidence is high and to
      suggest a strategy to prevent the disease. Twenty-one pregnant women with VZ were
      compared to two control groups. The first control group ( n =30) had normal
      pregnancy and no VZ. The second control group ( n =27) had VZ and no pregnancy.
      Assir region has a total population of 150 000 (Abha area). The incidence of VZ
      in pregnancy in Asir region during the study period was 0.23%, which is high if
      compared to other studies. In comparison to controls, cases had a significant
      increase in fever episodes, hospital admission, viral pneumonia and hospital
      stay. P values were <0.0001, <0.0001, <0.05 and <0.01, respectively.Also, VZ in
      pregnancy negatively affected the perinatal outcome as evidenced by a significant
      increase in congenital malformation and neonatal admission to NICU ( P <0.0001
      and <0.002, respectively). The high incidence of VZ during pregnancy can be
      explained by the social behaviour of the population under study. In a
      conservative society unmarried women rarely mix and contact with viral infections
      is minimal. After marriage and during pregnancy the social exposure of the non
      immune to cases becomes more frequent. Also, contact with cases was greatly
      enhanced by the social mixing in modern facilities such as schools, shopping
      centres and health facilities. Recently an effective VZ vaccine has been
      introduced successfully. It will be prudent to include the vaccine in the
      expanded program of immunisation already adopted by our health authorities. This
      will be cost-effective and many cases can be averted.

PMID- 12521905
TI  - Variations in the investigation and management of group B streptococcus in
      Scotland.
AB  - This article describes the practice of Scottish obstetricians in terms of their
      investigation and treatment of group B streptococcus (GBS). This was a postal
      questionnaire survey of all 125 consultant obstetricians in Scotland. We recorded
      indications for testing for GBS, categories of women to whom treatment is given
      empirically and following confirmed infection, type of antibiotic used, and
      timing and route of administration. No respondents screened all pregnant women
      but 97% screened some or all of those at highest risk. Three-quarters
      administered antibiotics empirically to women with intrapartum pyrexia. However,
      other high-risk groups were unlikely to receive treatment without confirmation of
      colonisation. Only one-third of respondents gave antibiotics to all women with
      confirmed GBS, and up to one-half withheld them from some colonised women in high
      risk groups. Contrary to US guidelines, only 29% tested for GBS using low vaginal
      swabs and only 13% administered intrapartum antibiotics intravenously. There are
      wide variations in investigating and treating GBS throughout Scotland. It is
      likely that similar variations exist throughout the United Kingdom. UK guidelines
      are required to reduce variations and ensure appropriate and effective
      management.

PMID- 12521906
TI  - Antenatal HIV screening in South West Nigeria: the client's perspective.
AB  - This study was carried out at the Obafemi Awolowo University Teaching Hospitals
      Complex, Ile-Ife, Nigeria with the aim of assessing pregnant clients' opinions on
      the issue of antenatal HIV screening which is at present very controversial in
      Nigeria. Five hundred and eighty-six clients were interviewed at the antenatal
      clinic using a close-ended questionnaire. Three hundred and eighty-five (67.8%)
      of the clients were found to have a good knowledge of HIV infection and were
      therefore included in the study sample. Of the clients, 75.1% and 61.5% accepted
      voluntary and mandatory screening, respectively. Respondent's reasons for
      accepting screening include prevention of transmission of infection to baby,
      husband and hospital staff, while reasons for objection to antenatal screening
      included financial implications, stigmatisation, fear of the outcome of the test
      and the right to choose. Four hundred and seventy-two (80.6%) and 389 (66.4%)
      patients will continue the pregnancy and not disclose the result if found
      positive at screening, respectively, while 11 (1.9%) expressed the view that they
      might contemplate suicide. Based on these findings, obstetricians in this
      locality are encouraged to modify the scope of antenatal care by gradually
      incorporating HIV screening as part of standard and screening procedure at
      booking or at the first visit.

PMID- 12521907
TI  - Correlation between maternal and infant HIV infection and low birth weight: a
      study in Mombasa, Kenya.
AB  - This article aimed to examine the association between maternal and infant HIV
      infection and low birth weight (LBW <2500 grams). Data from 8563 singleton
      liveborns in Mombasa, Kenya, were analysed. Maternal HIV infection was found in
      14.1% of the women and 9.6% of neonates had a birth weight of <2500 grams. In
      multivariate analysis, maternal HIV infection was independently associated with
      LBW (RR=1.46, 95% CI=1.20-1.79, P =0.0002). Maternal age, primiparity, sex of the
      baby, religion, syphilis infection, anaemia and previous history of stillbirth
      were also independently associated with LBW (RR: 1.32, 2.19, 1.44, 1.56, 1.61,
      1.31 and 1.69, respectively). The rate of intra-uterine HIV transmission was 5.1%
      and 20.1% of the exposed infants were infected during the intrapartum period.
      Intrapartum infected infants had a relative risk of LBW of 1.95 (95% CI=1.18
      2.87, P <0.01) compared to uninfected children, whereas the birth weight of
      infants infected in utero was not different from uninfected infants (RR=1.18, 95%
      CI=0.56-2.60, P=0.630). HIV infected mothers are more likely to have small
      babies, even after controlling for possible confounding factors. Low birth weight
      babies were more at risk for peripartum HIV transmission, but further research is
      needed to study mechanisms of transmission in relation to birth weight.

PMID- 12521908
TI  - Screening based on risk factors for gestational diabetes in an Asian population.
AB  - The results of glucose tolerance testing (OGTT) in 1004 consecutive women were
      examined with respect to risk factors for gestational diabetes mellitus (GDM).
      GDM was diagnosed in 41 of 1004 (4.08%) women. GDM was present in 7.8% of women
      aged over 35 years (compared to 3.1% if less than 35 years), in 8.1% women with a
      body mass index (BMI) >/=30 (compared to 3.6% if BMI <30) and in 5.2% of women
      with a family history of diabetes (compared to 3.9% in the absence of family
      history of diabetes). Past history of macrosomic babies (over 4 kg) was present
      in 12.1% of GDMs compared to 8.4% of non-diabetic pregnancies (NDP). A history of
      unexplained perinatal loss was present in 4.8% of GDMs compared to 2.2% of non
      diabetic pregnancies (NDP). Thirteen per cent of grandmultiprous women had GDM
      compared to 3.9% in women with low parity. The proportion of women who had more
      than one risk factor was 16.7%. A combination of one or all of these risk factors
      predicted GDM in only 24 of 41 (58.5%) cases. Selective testing on the basis of
      risk factors using WHO criteria for diagnosis of GDM would miss over 40% of all
      cases in our population. Hence, this study supports the policy of universal
      screening for GDM in populations similar to ours.

PMID- 12521909
TI  - Cardiac diseases during pregnancy: who will manage?
AB  - This study on 408 pregnant women with heart disease tried to audit the management
      of these women in a well equipped highrisk pregnancy unit. The outcome was nearly
      comparable to that obtained in series where the management was done in cardiology
      units.

PMID- 12521910
TI  - Immunolocalisation and endothelin-1 values In pre-eclampsia: an
      immunocytochemical study.
AB  - Maternal plasma ET-1 levels and the immunolocalisation of ET1 in the fetal
      membranes of pre-eclamptic primigravidae at >/=28 weeks, gestation were studied.
      The levels of maternal plasma ET1 and immunoreactive ET-1 were increased in pre
      eclampsia. Immunoreactive ET-1 was localised in the amnion, chorion and decidua
      of normal pregnant women as well as those with preeclampsia-eclampsia. Intense
      labelling was observed in moderate pre-eclampsia (BP 140/90 - 170/110 mmHg) with
      very intense labelling in severe pre-eclampsia (BP >170/110 mmHg), especially in
      the amniotic epithelium, chorionic villi, maternal blood vessels,
      cytotrophoblasts and giant cells of the decidua. The increased ET-1 levels
      demonstrated in fetal membranes of pre-eclamptic women are probably produced in a
      paracrine and/or autocrine manner, contributing to the hypertension, vasospasm
      and fetal growth restriction characteristic of the syndrome. A larger study would
      be required to show significant change in endothelin production in pre-eclampsia.

PMID- 12521911
TI  - Copper, zinc and magnesium status in hyperemesis gravidarum.
AB  - Plasma copper (Cu), zinc (Zn) and magnesium (Mg) levels were measured in three
      groups of women; (1) pregnant women suffering from hyperemesis gravidarum
      (HG)(n=43); (2) pregnant women with uncomplicated pregnancies (n=11) and (3) non
      pregnant women (n=11). Plasma Cu, Zn and Mg levels were measured by atomic
      absorbtion spectrophotometer. We determined that plasma Zn and Mg levels were
      lower in patients with HG and significant differences were noted between the
      control groups and HG patients (P < 0.05, P < 0.01). We still need further large
      cohort studies in order to understand if this is the cause or consequence of
      hyperemesis gravidarum.

PMID- 12521912
TI  - Changing trends in perinatal deaths at the Armed Forces Hospital, Riyadh, Saudi
      Arabia.
AB  - A total of 104522 babies were delivered at the Riyadh Armed Forces Hospital
      between 1979 and 1998, including 807 stillbirths and 658 neonatal deaths. The 20
      year period was divided into four 5-yearly intervals for comparative purposes.
      The overall Perinatal Mortality Rate (PMR) for infants weighing 500 grams or more
      ranged between 20.2 per 1000 in 1979 and 13 per 1000 in 1998. The lowest PMR of
      10.3 per 1000 was recorded in 1985. Thirty-one per cent of the perinatal deaths
      were unbooked. The corrected neonatal death rate (excluding congenital anomalies)
      dropped from 10.1 per 1000 in 1979 to 1.7 per 1000 live births in 1998 - The
      corrected stillbirth rate dropped from 12.1 per 1000 births in 1979 to six per
      1000 in 1998. Of the 807 stillbirths, 24.1% had lethal congenital anomalies while
      29.5% were unexplained, 4% had hydrops fetalis, 2% died as a consequence of
      toxaemia of pregnancy, 7.5% were associated with antepartum haemorrhage, 7.9%
      were mechanical, related to cord accident and ruptured uterus, 9.8% died as a
      consequence of maternal disease, 5.4% of intrapartum asphyxia and 6.4% placental
      insufficiency. Of the 658 neonatal deaths, 47.5% had lethal congenital anomalies,
      2% had hydrops fetalis, 7.6% died as a result of intrapartum asphyxia, 38% died
      as a result of prematurity with its complications of severe respiratory
      dysfunction and intraventricular and pulmonary haemorrhage, 4.1% died in NICU of
      secondary infection and 0.7% were unclassified. The overall PMR for infants
      weighing 500 grams or more was 14.1 per thousand. Congenital anomalies and low
      birth weight/prematurity accounted for 85.5% of the neonatal deaths. Congenital
      anomalies and unexplained deaths accounted for 53% of total stillbirths while
      maternal disease was responsible for 9.8% of total stillbirths. Reducing
      congenital anomalies and preventing prematurity and provision of good antenatal
      care will help in reducing PMR still further.

PMID- 12521913
TI  - Effects of hormone replacement therapy on the phospholipid composition of high
      density lipoproteins in postmenopausal women.
AB  - The beneficial effect of hormone replacement therapy (HRT) in reducing the risk
      of cardiovascular disease may be partly mediated by favourable changes in the
      phospholipid composition of high density lipoprotein (HDL) subclasses. In group
      A(oestrogen alone) HDL phosphatidylcholine increased (P<0.01), while 2 there was
      a decrease in HDL phosphaditylinositol (P<0.05) 2 and HDL
      phosphatidylethanolamine (P<0.01) compared with 2 controls (baseline). In the
      same group, HDL phosphatidylcholine 3 increased (P<0.01) and HDL
      phosphatidylethanolamine decreased (P<0.05). In group B (oestrogen plus
      progestogens), HDL phosphatidylcholine increased (P<0.001) while there were 2
      decreases in HDL sphingomyelin (P<0.01), HDL 2 2 phosphatidylserine (P<0.05), HDL
      phosphatidylethanolamine 2 (P<0.01) and HDL diphosphatidylglycerol (P<0.05). In
      the 2 same group, an increase in HDL phosphatidylcholine (P<0.01) 3 and HDL
      phosphatidylserine (P<0.01) were observed, as well 3 as a decrease in HDL
      phosphatidylethanolamine (P<0.001). 3 The significance of these results is
      discussed.

PMID- 12521914
TI  - 'See and treat' at colposcopy--achieving the standard.
AB  - The National Health Service Cervical Screening Programme has issued quality
      standards for the colposcopy service nationally. One standard is that for women
      who undergo treatment at their first colposcopy clinic visit, 90% should have
      proven cervical intra-epithelial neoplasia (CIN) on histology. We have assessed
      data from a teaching hospital colposcopy clinic over a 9-year period to assess
      the criteria that should be satisfied in order to achieve this target. We propose
      that only those women with severe dyskaryosis on the referral smear and a
      colposcopic appearance of CIN 2 or 3, or those in whom the colposcopic appearance
      suggests CIN 3 with any grade of dyskaryosis undergo treatment at their first
      visit.

PMID- 12521915
TI  - Treatment of menorrhagia before hysterectomy in a district general hospital. A
      retrospective review.
AB  - Between March 1996 and March 1998 236 women had a hysterectomy at Tameside
      District General Hospital. Of these, women, the indication in 132 was idiopathic
      menorrhagia and their treatments before hysterectomy were reviewed. It was found
      that luteal phase progestogens were the drug treatment of choice for menorrhagia
      by the general practitioners (GPs) and hospital doctors (46% and 40.5%,
      respectively). Fifty-two (39%) of the women had no medical treatment before
      hysterectomy while 38 (29%) had only one type of drug treatment. The decision to
      perform a hysterectomy was taken at the first clinic visit in 40 (30%) of the
      women and in 77 (58%) of them by the second visit. Transcervical resection of the
      endometrium (TCRE) was tried in 11% of the women, while none had the
      levonorgestrel impregnated intrauterine system (Mirena IUS) fitted. Objective
      assessment of menstrual loss was not performed before treatment. Our data suggest
      an early recourse to hysterectomy in the treatment of idiopathic menorrhagia and
      the hypothesis that hysterectomy follows failure of appropriate medical and
      alternative treatment of menorrhagia was not confirmed.

PMID- 12521916
TI  - Hysteroscopy: an alternative to dilatation and curettage in the diagnosis of
      postmenopausal bleeding.
AB  - Data were collected prospectively on 100 women suffering from postmenopausal
      bleeding who were investigated by hysteroscopy in a 5-month period. Women using
      hormone replacement therapy were excluded. The most common hysteroscopic finding
      was atrophy (44%). Other findings were: endometrial cysts (13%), endometrial
      polyp (12%) and adenocarcinoma (6%). The sample was not representative in 41% of
      cases and the most frequent histopathological diagnosis was inactive endometrium
      (14%). Other diagnoses were: inactive endometrium (14%), adenocarcinoma (6%),
      hyperplasia (7%), endometrial polyp (3%), proliferation (5%) and atrophy (4%),
      Endometrial sampling was not performed in 13% of the cases. General anaesthesia
      was not needed and complications were minimal. We support hysteroscopy as a
      routine alternative to dilatation and curettage in the diagnosis of
      postmenopausal bleeding.

PMID- 12521917
TI  - The prevalence and age distribution of ovarian cysts among women attending a
      London teaching hospital.

PMID- 12521922
TI  - Annual Meeting of the Northern Obstetrical and Gynaecological Society,
      MacGillivray Academic Centre, Aberdeen Maternity Hospital, 2 June 2000.

PMID- 12521924
TI  - Chronic cardiovascular and renal actions of leptin during hyperinsulinemia.
AB  - Hyperinsulinemia and hyperleptinemia occur concurrently in obese subjects, and
      both have been suggested to mediate increased blood pressure associated with
      excess weight gain. The goal of this study was to determine whether chronic
      hyperleptinemia exacerbates the effects of insulin on arterial pressure and renal
      function. Group I and II rats were infused with insulin (1.5 mU. kg(-1). min(-1))
      for 21 days while maintaining euglycemia. After 7 days of insulin infusion, group
      II rats received leptin (1.0 microg. kg(-1). min(-1)) for 7 days, concomitant
      with insulin. Insulin plus glucose infusion reduced food intake to 55 +/- 7% of
      control, while leptin + insulin lowered food intake further to 22 +/- 4% of the
      initial control. Insulin initially raised mean arterial pressure (MAP) by 12 +/-
      1 mmHg; then MAP declined to 5-8 mmHg above control during continued
      hyperinsulinemia. Leptin + insulin infusion increased MAP by 7 +/- 2 mmHg above
      the level observed in rats infused with insulin alone. Insulin raised heart rate
      (HR) by 17 +/- 5 beats/min, whereas leptin + insulin increased HR by 34 +/- 5
      beats/min. Thus leptin appears to increase the effects of insulin to suppress
      appetite and to raise arterial pressure and HR.

PMID- 12521925
TI  - Melatonin and activity rhythm responses to light pulses in mice with the Clock
      mutation.
AB  - Melatonin and wheel-running rhythmicity and the effects of acute and chronic
      light pulses on these rhythms were studied in Clock(Delta19) mutant mice
      selectively bred to synthesize melatonin. Homozygous melatonin-proficient
      Clock(Delta19) mutant mice (Clock(Delta19/Delta19)-MEL) produced melatonin
      rhythmically, with peak production 2 h later than the wild-type controls (i.e.,
      just before lights on). By contrast, the time of onset of wheel-running activity
      occurred within a 20-min period around lights off, irrespective of the genotype.
      Melatonin production in the mutants spontaneously decreased within 1 h of the
      expected time of lights on. On placement of the mice in continuous darkness, the
      melatonin rhythm persisted, and the peak occurred 2 h later in each cycle over
      the first two cycles, consistent with the endogenous period of the mutant. This
      contrasted with the onset of wheel-running activity, which did not shift for
      several days in constant darkness. A light pulse around the time of expected
      lights on followed by constant darkness reduced the expected 2-h delay of the
      melatonin peak of the mutants to approximately 1 h and advanced the time of the
      melatonin peak in the wild-type mice. When the Clock(Delta19/Delta19)-MEL mice
      were maintained in a skeleton photoperiod of daily 15-min light pulses, a higher
      proportion entrained to the schedule (57%) than melatonin-deficient mutants (9%).
      These results provide compelling evidence that mice with the Clock(Delta19)
      mutation express essentially normal rhythmicity, albeit with an underlying
      endogenous period of 26-27 h, and they can be entrained by brief exposure to
      light. They also raise important questions about the role of Clock in rhythmicity
      and the usefulness of monitoring behavioral rhythms compared with hormonal
      rhythms.

PMID- 12521926
TI  - Restricted feeding with scheduled sucrose access results in an upregulation of
      the rat dopamine transporter.
AB  - Recent studies suggest that the mesoaccumbens dopamine system undergoes
      neurochemical alterations as a result of restricted feeding conditions with
      access to sugars. This effect appears to be similar to the neuroadaptation
      resulting from drugs of abuse and may underlay some pathological feeding
      behaviors. To further investigate the cellular mechanisms of these alterations,
      the present study used quantitative autoradiography and in situ hybridization to
      assess dopamine membrane transporter (DAT) protein density and mRNA expression in
      restricted-fed and free-fed adult male rats. The restricted feeding regimen
      consisted of daily limited access to either a normally preferred sucrose solution
      (0.3 M) or a less preferred chow in a scheduled (i.e., contingent) fashion for 7
      days. Restricted-fed rats with the contingent sucrose access lost less body
      weight, ate more total food, and drank more fluid than free-fed, contingent food,
      or noncontingent controls. In addition, these animals had selectively higher DAT
      binding in the nucleus accumbens and ventral tegmental area. This increase in
      protein binding also was accompanied by an increase in DAT mRNA levels in the
      ventral tegmental area. In contrast to the restricted-fed groups, no differential
      effect in DAT regulation was observed across free-fed groups. The observed
      alteration in behavior and DAT regulation suggest that neuroadaptation in the
      mesoaccumbens dopamine system develops in response to repeated feeding on
      palatable foods under dietary constraints. This supports the notion that similar
      cellular changes may be involved in restrictive eating disorders and bingeing.

PMID- 12521927
TI  - Estrogen modulation of baroreflex function in conscious mice.
AB  - It has been suggested that estrogen modulates baroreflex regulation of autonomic
      function. The present study evaluated the effects of estrogen on baroreflex
      regulation of heart rate in response to changes in blood pressure with
      phenylephrine (PE), ANG II, and sodium nitroprusside (SNP) in a conscious mouse
      model. Males and ovariectomized females with (OvxE+) and without (OvxE-)
      estradiol replacement chronically implanted with arterial and venous catheters
      were used in these studies. The slope of the baroreflex bradycardic responses to
      PE was significantly facilitated in OvxE+ females (-7.65 +/- 1.37) compared with
      OvxE- females (-4.5 +/- 0.4). Likewise, the slope of the baroreflex bradycardic
      responses to ANG II was significantly facilitated in OvxE+ females (-7.97 +/-
      1.06) compared with OvxE- females (-4.8 +/- 1.6). Reflex tachycardic responses to
      SNP were comparable in all the groups. Finally, in male mice, the slope of ANG II
      induced baroreflex bradycardia (-5.17 +/- 0.95) was significantly less than that
      induced by PE (-8.50 +/- 0.92), but this ANG II-mediated attenuation of reflex
      bradycardia was not observed in the female mice. These data support the
      hypothesis that estrogen facilitates baroreflex function in female mice and
      suggest that ANG II-mediated acute blunting of baroreflex regulation of heart
      rate may be sex dependent.

PMID- 12521928
TI  - Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic
      conditions and demand-induced ischemia.
AB  - Metabolic interventions improve performance during demand-induced ischemia by
      reducing myocardial lactate production and improving regional systolic function.
      We tested the hypotheses that 1) stimulation of glycolysis would increase lactate
      production and improve ventricular wall motion, and 2) the addition of fatty acid
      oxidation inhibition would reduce lactate production and further improve
      contractile function. Measurements were made in anesthetized open-chest swine
      hearts. Three groups, hyperglycemia (HG), HG + oxfenicine (HG + Oxf), and control
      (CTRL), were treated under aerobic conditions and during demand-induced ischemia.
      During demand-induced ischemia, HG resulted in greater lactate production and
      tissue lactate content but had no significant effect on glucose oxidation. HG +
      Oxf significantly lowered lactate production and increased glucose oxidation
      compared with both the CTRL and HG groups. Myocardial energy efficiency was
      greater in the HG and HG + Oxf groups under aerobic conditions but did not change
      during demand-induced ischemia. Thus enhanced glycolysis resulted in increased
      energy efficiency under aerobic conditions but significantly enhanced lactate
      production with no further improvement in function during demand-induced
      ischemia. Partial inhibition of free fatty acid oxidation in the presence of
      accelerated glycolysis increased energy efficiency under aerobic conditions and
      significantly reduced lactate production and enhanced glucose oxidation during
      demand-induced ischemia.

PMID- 12521929
TI  - Effects of ovariectomy on aggregation, secretion, and metalloproteinases in
      porcine platelets.
AB  - Differences in the aggregation and release of growth factors including matrix
      metalloproteinases (MMPs) after loss of ovarian hormones could contribute to an
      exaggerated response to injury in arteries of ovariectomized animals. Therefore,
      experiments were designed to compare aggregation, dense granular ATP release,
      expression of MMPs (MMP-2, MMP-9, and MMP-14) and tissue inhibitors of
      metalloproteinase (TIMP-1 and TIMP-2) in circulating platelets from sexually
      mature (7 mo old) gonadally intact and ovariectomized (4 wk) female pigs. Numbers
      of circulating platelets did not change after ovariectomy, but the percentage of
      reticulated platelets increased significantly. Platelet aggregation and dense
      granular ATP secretion also increased significantly with ovariectomy. In platelet
      lysates, active MMP-2 increased, whereas MMP-14 significantly decreased, after
      ovariectomy; the expression of TIMP-1, TIMP-2, and P-selectin did not change.
      These results suggest that platelet turnover, aggregation, and ATP secretion
      increase with ovariectomy. Also, ovarian hormones selectively regulate the
      expression and activity of MMPs in porcine platelets. Increased platelet
      aggregation and activity of MMP-2 would alter platelet-platelet and platelet
      vessel wall interactions, contributing to an exaggerated response to injury with
      loss of ovarian hormones.

PMID- 12521930
TI  - B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP
      channel opening.
AB  - B-type natriuretic peptide (BNP) has been reported to be released from the
      myocardium during ischemia. We hypothesized that BNP mediates cardioprotection
      during ischemia-reperfusion and examined whether exogenous BNP limits myocardial
      infarction and the potential role of ATP-sensitive potassium (K(ATP)) channel
      opening. Langendorff-perfused rat hearts underwent 35 min of left coronary artery
      occlusion and 120 min of reperfusion. The control infarct-to-risk ratio was 44.8
      +/- 4.4% (means +/- SE). BNP perfused 10 min before ischemia limited infarct size
      in a concentration-dependent manner, with maximal protection observed at 10(-8) M
      (infarct-to-risk ratio: 20.1 +/- 5.2%, P < 0.01 vs. control), associated with a
      2.5-fold elevation of myocardial cGMP above the control value. To examine the
      role of K(ATP) channel opening, glibenclamide (10(-6) M), 5-hydroxydecanoate (5
      HD; 10(-4) M), or HMR-1098 (10(-5) M) was coperfused with BNP (10(-8) M).
      Protection afforded by BNP was abolished by glibenclamide or 5-HD but not by HMR
      1098, suggesting the involvement of putative mitochondrial but not sarcolemmal
      K(ATP) channel opening. We conclude that natriuretic peptide/cGMP/K(ATP) channel
      signaling may constitute an important injury-limiting mechanism in myocardium.

PMID- 12521931
TI  - High agonist-independent clearance of rabbit kinin B1 receptors in cultured
      cells.
AB  - We hypothesized that the inducible kinin B(1) receptor (B(1)R) is rapidly cleared
      from cells when its synthesis subsides. The agonist-independent degradation of
      the rabbit B(1)Rs and related B(2) receptors (B(2)Rs) was investigated.
      Endocytosis of the B(1)R-yellow fluorescent protein (YFP) conjugate was more
      intense than that of B(2)R-green fluorescent protein (GFP) based on fluorescence
      accumulation in HEK 293 cells treated with a lysosomal inhibitor. The cells
      expressing B(1)R-YFP contained more GFP/YFP-sized degradation product(s) than
      those expressing B(2)R-GFP (immunoblot, antibodies equally reacting with both
      fluorescent proteins). The binding site density of B(1)R-YFP decreased in the
      presence of protein synthesis or maturation inhibitors (anisomycin, brefeldin A),
      whereas that of B(2)R-GFP remained constant. Wild-type B(1)Rs were also cleared
      faster than B(2)Rs in rabbit smooth muscle cells treated with metabolic
      inhibitors. Contractility experiments based on brefeldin A-treated isolated
      rabbit blood vessels also functionally support that B(1)Rs are more rapidly
      eliminated than B(2)Rs (decreased maximal effect of agonist over 2 h). The highly
      regulated B(1)R is rapidly degraded, relative to the constitutive B(2)R.

PMID- 12521932
TI  - EDHF-mediated vasodilation involves different mechanisms in normotensive and
      hypertensive rat lungs.
AB  - The role of endothelium-derived hyperpolarizing factor (EDHF) in regulating the
      pulmonary circulation and the participation of cytochrome P-450 (CYP450) activity
      and gap junction intercellular communication in EDHF-mediated pulmonary
      vasodilation are unclear. We tested whether tonic EDHF activity regulated
      pulmonary vascular tone and examined the mechanism of EDHF-mediated pulmonary
      vasodilation induced by thapsigargin in salt solution-perfused normotensive and
      hypoxia-induced hypertensive rat lungs. After blockade of both cyclooxygenase and
      nitric oxide synthase, inhibition of EDHF with charybdotoxin plus apamin did not
      affect either normotensive or hypertensive vascular tone or acute hypoxic
      vasoconstriction but abolished thapsigargin vasodilation in both groups of lungs.
      The CYP450 inhibitors 7-ethoxyresorufin and sulfaphenazole and the gap junction
      inhibitor palmitoleic acid, but not 18alpha-glycyrrhetinic acid, inhibited
      thapsigargin vasodilation in normotensive lungs. None of these agents inhibited
      the vasodilation in hypertensive lungs. Thus tonic EDHF activity does not
      regulate either normotensive or hypertensive pulmonary vascular tone or acute
      hypoxic vasoconstriction. Whereas thapsigargin-induced EDHF-mediated vasodilation
      in normotensive rat lungs involves CYP450 activity and might act through gap
      junctions, the mechanism of vasodilation is apparently different in hypertensive
      lungs.

PMID- 12521933
TI  - Normovolemic hemodilution with Hb vesicle solution attenuates hypoxia in ischemic
      hamster flap tissue.
AB  - The aim of this study was to test whether oxygenation in acutely ischemic,
      collateralized tissue may be improved by normovolemic hemodilution with a
      solution containing liposome-encapsulated human Hb (HbV). A skin flap model in
      anesthetized hamsters was used, which consisted of two parts receiving either
      anatomic or collateral perfusion. Microhemodynamics were investigated with
      intravital microscopy. Partial tissue oxygen tension was measured with a Clark
      type microprobe. Hemodilution was obtained by exchanging 50% of the total blood
      volume with HbV suspended in 8% human serum albumin (HSA8) or 6% Dextran 70
      (Dx70). The size of the vesicles was 276 nm, the P(50) was 22 mmHg, and the Hb
      concentration of the solutions was 7.5 g/dl. Colloid osmotic pressure and
      viscosity were 49.9 mmHg and 8.7 cP for HbV-Dx70 and 40.0 mmHg and 2.9 cP for HbV
      HSA8, respectively. Hemodilution with HbV-Dx70 led to an increase in
      microvascular blood flow in the ischemic microvessels to maximally 158% (median,
      P < 0.01), whereas blood flow remained virtually unchanged after hemodilution
      with HbV-HSA8. In the ischemic tissue, oxygen tension was improved from 11.9 to
      17.0 mmHg (P < 0.01) after hemodilution with HbV-Dx70 but remained virtually
      unchanged after hemodilution with HbV-HSA8. Our study suggests that the
      oxygenation in acutely ischemic, collateralized tissue may be improved by
      normovolemic hemodilution with HbV suspended in Dx70. The effect was achieved by
      an increase in microcirculatory blood flow related to the rheological properties
      of the suspending medium.

PMID- 12521934
TI  - In vivo visualization of subendocardial arteriolar response in renovascular
      hypertensive hearts.
AB  - Time-sequential responses to endothelium-dependent and -independent vasodilators
      and angiotensin-converting enzyme (ACE) inhibitors were studied in the
      subendocardial arterioles (Endo) of canine renovascular hypertension (HT)
      compared with subepicardial arterioles (Epi; both <120 microm) by charge-coupled
      device intravital microscope. Vascular responses to acetylcholine, papaverine,
      and cilazaprilat were compared between normotensive (NT) and HT dogs [4 wk and 12
      wk of HT (4wHT and 12wHT)]. The acetylcholine-induced vasodilation of Endo in
      both 4wHT and 12wHT was smaller than that of NT (both P < 0.01 vs. 4wHT and
      12wHT), and that of Epi was smaller than that of NT only in 12wHT (P < 0.05). The
      papaverine-induced vasodilation of Endo, but not Epi, was impaired only in 12wHT
      (both P < 0.01 vs. NT and 4wHT). Vasodilation by cilazaprilat remained unchanged
      at 4wHT and 12wHT in both Epi and Endo. In conclusion, at the early stage, the
      endothelium-dependent response of Endo was impaired, whereas at the later stage,
      the endothelium-dependent and -independent responses of Endo and the endothelium
      dependent response of Epi were impaired. However, the vasodilatory responses to
      the ACE inhibitor were maintained in both Endo and Epi of HT.

PMID- 12521935
TI  - Microinjection of a cannabinoid receptor antagonist into the NTS increases
      baroreflex duration in dogs.
AB  - Baroreceptor afferent fibers synapse in the nucleus tractus solitarius (NTS) of
      the medulla. Neuronal cannabinoid (CB)(1) receptors are expressed in the NTS and
      central administration of CB(1) receptor agonists affect blood pressure (BP) and
      heart rate. In addition, there is evidence that endocannabinoids are produced in
      the brain stem. This study examined whether changes in CB(1) receptor activity in
      the NTS modulated the baroreceptor reflex, contributing to changes seen in BP and
      heart rate. Baroreflexes were evoked in anesthetized dogs by pressure ramp
      stimulations of the isolated carotid sinus before and after microinjection of
      CB(1) receptor agonist WIN-55212-2 (1.25-1.50 pmol) or antagonist SR-141716 (2.5
      3.0 pmol) into cardiovascular regions of the NTS. Microinjection of the SR-141716
      did not affect baseline BP or baroreflex sensitivity. However, SR-141716
      significantly prolonged the time needed to return to the baseline level of BP
      after the pressure ramp. Microinjection of WIN-55212-2 had no effect on the
      baroreflex. These data suggest that endocannabinoids can modulate the
      excitability of NTS neurons involved in the baroreceptor reflex, leading to
      modulation of baroreflex regulation.

PMID- 12521936
TI  - Effects of nicotine and dietary salt on a learned blood pressure response in Dahl
      S rats.
AB  - We examined the effects of chronic nicotine exposure and dietary salt on the
      arterial blood pressure (BP) changes learned in response to an acute behavioral
      stress in the Dahl salt-sensitive rat. Four groups were tested: low salt +
      vehicle; low salt + nicotine; high salt + vehicle; and high salt + nicotine. Rats
      were fed a low-salt (0.08% NaCl) or a high-salt (8% NaCl) diet for 4 wk; 2.4 mg.
      kg(-1). day(-1) nicotine or vehicle was given via an implanted osmotic minipump
      for the last 2 wk. All rats were conditioned by following one tone (CS+) with a
      0.5-s tail shock; another tone (CS-) was never followed by shock. CS+ in low salt
      + vehicle and high salt + vehicle-treated rats evoked an initial arterial BP
      increase (C(1)), a component of the startle response, and an ensuing, smaller,
      but more sustained, pressor response (C(2)), which is acquired with training. In
      these rats, both C(1) and C(2) evoked by CS- were significantly smaller than
      those to CS+, demonstrating that these groups discriminated between the two
      tests. Conversely, although the low salt + nicotine-treated rats had both the
      C(1) and C(2) components of the conditional arterial pressure response, they did
      not discriminate between CS+ and CS-. Finally, the high salt + nicotine group
      failed to both discriminate between tones and acquire (i.e., learn) the C(2)
      response. The unconditional response to shock did not differ between groups. We
      conclude that combined exposure to high salt and to nicotine inhibits the salt
      sensitive animal's acquisition of a learned conditional BP response, perhaps
      because nicotine acts preferentially on those central processes required for
      associative learning versus those involved in orientating to external stimuli.

PMID- 12521937
TI  - A new method for assessing arteriolar diameter and hemodynamic resistance using
      image analysis of vessel lumen.
AB  - To characterize the nonuniform diameter response in a blood vessel after a given
      stimulus (e.g., arteriolar conducted response), frequent serial diameter
      measurements along the vessel length are required. We used an advanced image
      analysis algorithm (the "discrete dynamic contour") to develop a quick, reliable
      method for serial luminal diameter measurements along the arteriole visualized by
      intravital video microscopy. With the use of digitized images of the arteriole
      and computer graphics, the method required an operator to mark the image of the
      two inner edges of the arteriole at several places along the arteriolar length.
      The algorithm then "filled in" these marks to generate two continuous contours
      that "hugged" these edges. A computer routine used these contours to determine
      luminal diameters every 20 microm. Based on these diameters and on Poiseuille's
      law, the routine also estimated the hemodynamic resistance of the blood vessel.
      To demonstrate the usefulness of the method, we examined the character of spatial
      decay of KCl-induced conducted constriction along approximately 500-microm-long
      arteriolar segments and the KCl-induced increase in hemodynamic resistance
      computed for these segments. The decay was only modestly fitted by a simple
      exponential, and the computed increase in resistance (i.e., 5- to 70-fold) was
      only modestly predicted by resistance increase based on our mathematical model
      involving measurements at two arteriolar sites (Tyml K, Wang X, Lidington D, and
      Oullette Y. Am J Physiol Heart Circ Physiol 281: H1397-H1406, 2001). We conclude
      that our method provides quick, reliable serial diameter measurements. Because
      the change in hemodynamic resistance could serve as a sensitive index of
      conducted response, use of this index in studies of conducted response may lead
      to new mechanistic insights on the response.

PMID- 12521938
TI  - Human SM22 alpha BAC encompasses regulatory sequences for expression in vascular
      and visceral smooth muscles at fetal and adult stages.
AB  - The SM22 alpha gene has widely been used to study the regulatory mechanisms of
      smooth muscle cell (SMC) gene expression during cardiovascular development. To
      determine the regulatory mechanisms for the evolutionarily conserved human SM22
      alpha (hSM22 alpha) gene, we demonstrated that 445 bp upstream DNA sequences of
      hSM22 alpha gene exhibited a high transcriptional activity in arterial SMC, not
      in venous nor in visceral SMCs during embryogensis. However, this promoter was
      gradually turned off in adulthood. Inclusion of the first intron in this promoter
      suppressed the promoter activity in pulmonary trunk arterial SMCs, whereas the
      expression in other systemic vasculature remained similar to that of the hSM22
      445 promoter during the fetal and adult stages. To determine whether additional
      sequences are required for SM22 alpha expression in all subtypes of SMCs, we
      examined the expression of a bacterial artificial chromosome containing the hSM22
      alpha locus in transgenic mice. The hSM22 alpha transgene showed similar
      developmental expression patterns as the endogenous mouse SM22 alpha gene,
      suggesting that this bacterial artificial chromosome contains essential
      regulatory sequences for its expression in arterial, venous, and visceral tissues
      during development.

PMID- 12521939
TI  - Cardiac enkephalins interrupt vagal bradycardia via delta 2-opioid receptors in
      sinoatrial node.
AB  - Local cardiac opioids appear to be important in determining the quality of vagal
      control of heart rate. Introduction of the endogenous opioid methionine
      enkephalin-arginine-phenylalanine (MEAP) into the interstitium of the canine
      sinoatrial node by microdialysis attenuates vagally mediated bradycardia through
      a delta-opioid receptor mechanism. The following studies were conducted to test
      the hypothesis that a delta(2)-opiate receptor subtype mediates the interruption
      of vagal transmission. Twenty mongrel dogs were anesthetized and instrumented
      with microdialysis probes inserted into the sinoatrial node. Vagal frequency
      responses were performed at 1, 2, and 3 Hz during vehicle infusion and during
      treatment with the native agonist MEAP, the delta(1)-opioids 2-methyl-4aa-(3
      hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydroquinolino[2,3,3- g]isoquinoline
      (TAN-67) and [d-pen(2,5)]-enkephalin (DPDPE), and the delta(2) opioid deltorphin
      II. The vagolytic effects of intranodal MEAP and deltorphin were then challenged
      with the delta(1)- and delta(2)-opioid receptor antagonists 7
      benzylidenenaltrexone (BNTX) and naltriben, respectively. Although the positive
      control deltorphin II was clearly vagolytic in each experimental group, TAN-67
      and DPDPE were vagolytically ineffective in the same animals. In contrast, TAN-67
      improved vagal bradycardia by 30-35%. Naltriben completely reversed the vagolytic
      effects of MEAP and deltorphin. BNTX was ineffective in this regard but did
      reverse the vagal improvement observed with TAN-67. These data support the
      hypothesis that the vagolytic effect of the endogenous opioid MEAP was mediated
      by delta(2)-opioid receptors located in the sinoatrial node. These data also
      support the existence of vagotonic delta(1)-opioid receptors also in the
      sinoatrial node.

PMID- 12521940
TI  - NONOates regulate KCl cotransporter-1 and -3 mRNA expression in vascular smooth
      muscle cells.
AB  - Nitric oxide (NO) donors regulate KCl cotransport (KCC) activity and
      cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in sheep erythrocytes and
      in primary cultures of rat vascular smooth muscle cells (VSMCs), respectively. In
      this study, we used NONOates as rapid and slow NO releasers to provide direct
      evidence implicating NO as a regulator of KCC3 gene expression at the mRNA level.
      In addition, we used the expression of KCC3 mRNA to further investigate the
      mechanism of action of these NO donors at the cellular level. Treatment of VSMCs
      with rapid NO releasers, like NOC-5 and NOC-9, as well as with the direct NO
      independent soluble guanylyl cyclase (sGC) stimulator YC-1, acutely increased
      KCC3 mRNA expression in a concentration- and time-dependent manner. The slow NO
      releaser NOC-18 had no effect on KCC3 gene expression. A specific NO scavenger
      completely prevented the NONOate-induced KCC3 mRNA expression. Inhibition of sGC
      with LY-83583 blocked the NONOate- and YC-1-induced KCC3 mRNA expression. This
      study shows that in primary cultures of rat VSMCs, the fast NO releasers NOC-9
      and NOC-5, but not the slow NO releaser NOC-18, acutely upregulate KCC3 mRNA
      expression in a NO/sGC-dependent manner.

PMID- 12521941
TI  - Role of paraventricular nucleus in regulation of sympathetic nerve frequency
      components.
AB  - Autospectral and coherence analyses were used to determine the role of and
      interactions between paraventricular nucleus (PVN) nitric oxide, gamma
      aminobutyric acid (GABA), and the N-methyl-D-aspartic acid (NMDA)-glutamate
      receptor in regulation of sympathetic nerve discharge (SND) frequency components
      in anesthetized rats. Four observations were made. First, PVN microinjection of
      bicuculline (BIC) (GABA(A) receptor antagonist), but not single PVN injections of
      NMDA (excitatory amino acid) or N(G)-monomethyl-L-arginine (L-NMMA; a nitric
      oxide synthase inhibitor), altered SND frequency components. Second, combined PVN
      microinjections of L-NMMA and NMDA changed the SND bursting pattern; however, the
      observed pattern change was different from that produced by PVN BIC and not
      observed after sinoaortic denervation. Third, PVN microinjection of kynurenic
      acid prevented and reversed BIC-induced changes in the SND bursting pattern.
      Finally, vascular resistance (renal and splenic) was significantly increased
      after PVN BIC microinjection despite the lack of change in the level of renal and
      splenic SND. These data demonstrate that the PVN contains the neural substrate
      for altering SND frequency components and suggest complex interactions between
      specific PVN neurotransmitters and between PVN neurotransmitters and the arterial
      baroreceptor reflex in SND regulation.

PMID- 12521942
TI  - Effects of nitric oxide on red blood cell deformability.
AB  - In addition to its known action on vascular smooth muscle, nitric oxide (NO) has
      been suggested to have cardiovascular effects via regulation of red blood cell
      (RBC) deformability. The present study was designed to further explore this
      possibility. Human RBCs in autologous plasma were incubated for 1 h with NO
      synthase (NOS) inhibitors [N(omega)-nitro-l-arginine methyl ester (l-NAME) and S
      methylisothiourea], NO donors [sodium nitroprusside (SNP) and diethylenetriamine
      (DETA)-NONOate], an NO precursor (l-arginine), soluble guanylate cyclase
      inhibitors (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one and methylene blue), and
      a potassium channel blocker [triethylammonium (TEA)]. After incubation, RBC
      deformability at various shear stresses was determined by ektacytometry. Both NOS
      inhibitors significantly reduced RBC deformability above a threshold
      concentration, whereas the NO donors increased deformability at optimal
      concentrations. NO donors, as well as the NO precursor l-arginine and the
      potassium blocker TEA, were able to reverse the effects of NOS inhibitors.
      Guanylate cyclase inhibition reduced RBC deformation, with both SNP and DETA
      NONOate able to reverse this effect. These results thus indicate the importance
      of NO as a determinant of RBC mechanical behavior and suggest its regulatory role
      for normal RBC deformability.

PMID- 12521943
TI  - Dietary n-3 PUFAs affect the blood pressure rise and cardiac impairments in a
      hyperinsulinemia rat model in vivo.
AB  - The cardiovascular consequences of eicosapentaenoic acid (EPA)- and
      docosahexaenoic acid (DHA)-specific intake were evaluated in vivo in a
      hyperinsulinemia (HI) model induced by dietary fructose intake. Wistar rats were
      fed a diet containing (or not for control) either EPA or DHA. The rise in blood
      pressure (BP), heart rate, and ECG were continuously monitored using an intra
      abdominal telemetry system. The myocardial phospholipid fatty acid profile was
      significantly affected by DHA intake but less by EPA intake. The data indicated a
      reduced rise in BP in both DHA and EPA HI groups compared with controls. This
      result was confirmed by tail-cuff measurement after 5 wk [133.3 +/- 1.67 and
      142.5 +/- 1.12 mmHg in n-3 polyunsaturated fatty acid (PUFA) and control groups,
      respectively], whereas n-3 PUFA did not affect BP in non-HI rats (116.3 +/- 3.33
      mmHg). The heart rate was lower in the HI DHA group than in the other two dietary
      HI groups. Moreover, DHA induced a significantly shorter QT interval. It is
      concluded that the cardioactive component of fish oils is DHA through a mechanism
      that may involve the cardiac adrenergic system.

PMID- 12521944
TI  - NO produced by endothelial NO synthase is a mediator of delayed preconditioning
      induced endothelial protection.
AB  - Preconditioning with brief periods of ischemia-reperfusion (I/R) induces a
      delayed protection of coronary endothelial cells against reperfusion injury. We
      assessed the possible role of nitric oxide (NO) produced during prolonged I/R as
      a mediator of this endothelial protection. Anesthetized rats were subjected to 20
      min cardiac ischemia/60-min reperfusion, 24 h after sham surgery or cardiac
      preconditioning (1 x 2-min ischemia/5-min reperfusion and 2 x 5-min ischemia/5
      min reperfusion). The nonselective NO synthase (NOS) inhibitor l-NAME, the
      selective inhibitors of neuronal (7-nitroindazole) or inducible (1400W) NOS, or
      the peroxynitrite scavenger seleno-l-methionine were administered 10 min before
      prolonged ischemia. Preconditioning prevented the reperfusion-induced impairment
      of coronary endothelium-dependent relaxations to acetylcholine (maximal
      relaxation: sham 77 +/- 3; I/R 44 +/- 6; PC 74 +/- 5%). This protective effect
      was abolished by l-NAME (41 +/- 7%), whereas 7-NI, 1400W or seleno-l-methionine
      had no effect. The abolition of preconditioning by l-NAME, but not by selective
      nNOS or iNOS inhibition, suggests that NO produced by eNOS is a mediator of
      delayed endothelial preconditioning.

PMID- 12521945
TI  - Effect of blockade of endogenous angiotensin II on baroreflex function in
      conscious diabetic rats.
AB  - Little is known about baroreflex control of renal nerve sympathetic activity
      (RSNA) or the effect of angiotensin II (ANG II) on the baroreflex in diabetes. We
      examined baroreflex control of RSNA and heart rate (HR) in conscious, chronically
      instrumented rats 2 wk after citrate vehicle (normal) or 55 mg/kg iv
      streptozotocin (diabetic) before and after losartan (5 mg/kg iv) or enalapril
      (2.5 mg/kg iv). Resting HR and RSNA were lower in diabetic versus normal rats.
      The range of baroreflex control of HR and the gain of baroreflex-mediated
      bradycardia were impaired in diabetic rats. Maximum gain was unchanged. The
      baroreflex control of RSNA was reset to lower pressures in the diabetic rats but
      remained otherwise unchanged. Losartan decreased mean arterial pressure (MAP) and
      increased HR and RSNA in both groups but had no influence on the baroreflex.
      Enalapril decreased MAP only in normal rats, yet the increase in HR and RSNA was
      similar in both groups. Thus in diabetic rats enalapril produced a pressure
      independent increase in HR and RSNA. Enalapril exerted no effect on the
      baroreflex control of HR or RSNA in either group. These data indicate that in
      conscious rats resting RSNA is lower but baroreflex control of RSNA is preserved
      after 2 wk of diabetes. At this time, the baroreflex control of HR is already
      impaired and blockade of endogenous ANG II does not improve this dysfunction.

PMID- 12521946
TI  - Evidence for association of coronary sinus levels of hepatocyte growth factor and
      collateralization in human coronary disease.
AB  - The therapeutic use of angiogenic factors to protect ischemic myocardium is
      limited by our incomplete understanding of their endogenous production. We
      determined the association between angiogenic factors and collateral formation in
      patients with coronary artery disease (CAD). A total of 71 patients underwent
      catheterization with sampling of the pulmonary artery, aorta, and coronary sinus
      (CS) to determine the levels of vascular endothelial growth factor (VEGF) and
      hepatocyte growth factor (HGF). VEGF and HGF levels were not different in the
      three vascular sites, suggesting that the heart is not a major source of these
      cytokines in the circulation. CS VEGF and HGF levels were similar in patients
      with and without CAD. Elevated CS HGF levels were associated with collateral
      formation, whereas VEGF levels were not. Additionally, CS HGF was significantly
      elevated in patients with left ventricular dysfunction. These data map for the
      first time the concentration of endogenous angiogenic factors in the coronary
      circulation and support further studies to determine whether HGF may be an
      endogenous cardioprotective angiogenic factor.

PMID- 12521947
TI  - CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle
      angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis
      induced by electrical stimulation in skeletal muscle. Less is known about the
      role of arachidonic acid metabolites in the control of growth of blood vessels in
      vivo. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20
      HETE) on the angiogenesis induced by electrical stimulation in skeletal muscle.
      The tibialis anterior and extensor digitorum longus muscles of rats were
      stimulated for 7 days. Electrical stimulation significantly increased the 20-HETE
      formation and angiogenesis in the muscles, which was blocked by chronic treatment
      with N-hydroxy-N'-(4-butyl-2-methylphenol)formamidine (HET0016) or 1
      aminobenzotriazole (ABT). Chronic treatment with either HET0016 or ABT did not
      block the increases in VEGF protein expression in both muscles. To analyze the
      role of VEGF on 20-HETE formation, additional rats were treated with VEGF
      neutralizing antibody (VEGF Ab). VEGF Ab blocked the increases of 20-HETE
      formation induced by stimulation. These results place 20-HETE in the downstream
      signaling pathway for angiogenesis and show that both VEGF and 20-HETE are
      involved in the angiogenesis induced by electrical stimulation in skeletal
      muscle.

PMID- 12521948
TI  - Fractal and periodic heart rate dynamics in fetal sheep: comparison of
      conventional and new measures based on fractal analysis.
AB  - The physiological significance of spectral and fractal components of spontaneous
      heart rate (HR) variability in the fetus remains unclear. To examine the
      relationship between circadian rhythms in different measures of HR variability, R
      R interval time series obtained by fetal ECGs were recorded continuously over 24
      h in five pregnant sheep at 116-125 days gestation. Conventional measures of
      short-term (STV) and long-term variability (LTV), low-frequency (LF; 0.025-0.15
      cycles/beat) and high-frequency (HF; 0.2-0.5 cycles/beat) spectral powers, the LF
      to-HF ratio, and fractal dimension values were calculated from 24-h ECG
      recordings and quantified every 60 min. STV, LTV, and LF and HF spectral powers
      were minimal during the day but increased significantly to their highest values
      at night. We found a significant positive correlation between these measures,
      whereas the cosinor method showed significant similarity between their circadian
      rhythm patterns. Fetal R-R intervals also exhibited fractal structures. Fetal HR
      variability had a fractal structure, which was similar between day and night.
      These results suggested that the circadian rhythms exhibited by STV and LTV
      during the day were mainly due to changes in frequency components rather than to
      fractal components of fetal HR fluctuation.

PMID- 12521949
TI  - Drug treatment of hypertension.

PMID- 12521950
TI  - Intimate examinations and other ethical challenges in medical education.

PMID- 12521952
TI  - Testing new pharmaceutical products in children.

PMID- 12521953
TI  - Racism and health.

PMID- 12521954
TI  - US doctor warns of misuse of prescribed stimulants.

PMID- 12521955
TI  - Drug companies defend rewards to doctors for switching treatments.

PMID- 12521956
TI  - Animal rights activist is removed from government committee.

PMID- 12521957
TI  - More doctors is not the answer to the EU Working Time Directive.

PMID- 12521958
TI  - Cigarette possession becomes illegal for Novia Scotia's under 19s.

PMID- 12521962
TI  - Israeli committee maps out healthcare reforms.

PMID- 12521963
TI  - Drug linked to child deaths is still available in India.

PMID- 12521966
TI  - Being "tired of life" is not grounds for euthanasia.

PMID- 12521968
TI  - Multifactorial intervention after a fall in older people with cognitive
      impairment and dementia presenting to the accident and emergency department:
      randomised controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of multifactorial intervention after a
      fall in older patients with cognitive impairment and dementia attending the
      accident and emergency department. DESIGN: Randomised controlled trial.
      PARTICIPANTS: 274 cognitively impaired older people (aged 65 or over) presenting
      to the accident and emergency department after a fall: 130 were randomised to
      assessment and intervention and 144 were randomised to assessment followed by
      conventional care (control group). SETTING: Two accident and emergency
      departments, Newcastle upon Tyne. MAIN OUTCOME MEASURES: Primary outcome was
      number of participants who fell in year after intervention. Secondary outcomes
      were number of falls (corrected for diary returns), time to first fall, injury
      rates, fall related attendances at accident and emergency department, fall
      related hospital admissions, and mortality. RESULTS: Intention to treat analysis
      showed no significant difference between intervention and control groups in
      proportion of patients who fell during 1 year's follow up (74% (96/130) and 80%
      (115/144), relative risk ratio 0.92, 95% confidence interval 0.81 to 1.05). No
      significant differences were found between groups for secondary outcome measures.
      CONCLUSIONS: Multifactorial intervention was not effective in preventing falls in
      older people with cognitive impairment and dementia presenting to the accident
      and emergency department after a fall.

PMID- 12521969
TI  - Effect on hip fractures of increased use of hip protectors in nursing homes:
      cluster randomised controlled trial.
AB  - OBJECTIVE: To assess the effects of an intervention programme designed to
      increase use of hip protectors in elderly people in nursing homes. DESIGN:
      Cluster randomised controlled trial with 18 months of follow up. SETTING: Nursing
      homes in Hamburg (25 clusters in intervention group; 24 in control group).
      PARTICIPANTS: Residents with a high risk of falling (459 in intervention group;
      483 in control group). INTERVENTION: Single education session for nursing staff,
      who then educated residents; provision of three hip protectors per resident in
      intervention group. Usual care optimised by brief information to nursing staff
      about hip protectors and provision of two hip protectors per cluster for
      demonstration purposes. MAIN OUTCOME MEASURE: Incidence of hip fractures.
      RESULTS: Mean follow up was 15 months for the intervention group and 14 months
      for the control group. In total 167 residents in the intervention group and 207
      in the control group died or moved away. There were 21 hip fractures in 21 (4.6%)
      residents in the intervention group and 42 hip fractures in 39 (8.1%) residents
      in the control group (relative risk 0.57, absolute risk difference -3.5%, 95%
      confidence interval -7.3% to 0.3%, P=0.072). After adjustment for the cluster
      randomisation the proportions of fallers who used a hip protector were 68% and
      15% respectively (mean difference 53%, 38% to 67%, P=0.0001). There were 39 other
      fractures in the intervention group and 38 in the control group. CONCLUSION: The
      introduction of a structured education programme and the provision of free hip
      protectors in nursing homes increases the use of protectors and may reduce the
      number of hip fractures.

PMID- 12521970
TI  - Acknowledgement of "no fault" medical injury: review of patients' hospital
      records in New Zealand.

PMID- 12521971
TI  - Review of deaths related to taking ecstasy, England and Wales, 1997-2000.

PMID- 12521972
TI  - Recent changes in lung cancer incidence for south Asians: a population based
      register study.

PMID- 12521973
TI  - Research pointers: Platelet responsiveness to aspirin in patients with
      hyperlipidaemia.

PMID- 12521974
TI  - Secondary prevention clinics for coronary heart disease: four year follow up of a
      randomised controlled trial in primary care.
AB  - OBJECTIVES: To evaluate the effects of nurse led clinics in primary care on
      secondary prevention, total mortality, and coronary event rates after four years.
      DESIGN: Follow up of a randomised controlled trial by postal questionnaires and
      review of case notes and national datasets. SETTING: Stratified, random sample of
      19 general practices in north east Scotland. PARTICIPANTS: 1343 patients (673
      intervention and 670 control) under 80 years with a working diagnosis of coronary
      heart disease but without terminal illness or dementia and not housebound.
      INTERVENTION: Nurse led secondary prevention clinics promoted medical and
      lifestyle components of secondary prevention and offered regular follow up for
      one year. MAIN OUTCOME MEASURES: Components of secondary prevention (aspirin,
      blood pressure management, lipid management, healthy diet, exercise, non
      smoking), total mortality, and coronary events (non-fatal myocardial infarctions
      and coronary deaths). RESULTS: Mean follow up was at 4.7 years. Significant
      improvements were shown in the intervention group in all components of secondary
      prevention except smoking at one year, and these were sustained after four years
      except for exercise. The control group, most of whom attended clinics after the
      initial year, caught up before final follow up, and differences between groups
      were no longer significant. At 4.7 years, 100 patients in the intervention group
      and 128 in the control group had died: cumulative death rates were 14.5% and
      18.9%, respectively (P=0.038). 100 coronary events occurred in the intervention
      group and 125 in the control group: cumulative event rates were 14.2% and 18.2%,
      respectively (P=0.052). Adjusting for age, sex, general practice, and baseline
      secondary prevention, proportional hazard ratios were 0.75 for all deaths (95%
      confidence intervals 0.58 to 0.98; P=0.036) and 0.76 for coronary events (0.58 to
      1.00; P=0.049) CONCLUSIONS: Nurse led secondary prevention improved medical and
      lifestyle components of secondary prevention and this seemed to lead to
      significantly fewer total deaths and probably fewer coronary events. Secondary
      prevention clinics should be started sooner rather than later.

PMID- 12521975
TI  - Skin scarring.

PMID- 12521976
TI  - ABC of antithrombotic therapy: Antithrombotic therapy in special circumstances.
      II-In children, thrombophilia, and miscellaneous conditions.

PMID- 12521977
TI  - The ethics of intimate examinations-teaching tomorrow's doctors.

PMID- 12521978
TI  - Preventing obesity. Prevention starts in infancy.

PMID- 12521979
TI  - Patient centred approach may help in hypertension.

PMID- 12521981
TI  - Involving patients can work in home blood glucose testing.

PMID- 12521982
TI  - Violence as a public health problem. Combined approach is needed.

PMID- 12521983
TI  - Vaccine induced protection against hepatitis B.

PMID- 12521984
TI  - Case report showed Muehrcke's nails, not Beau's lines.

PMID- 12521985
TI  - Referees make journal clubs fun.

PMID- 12521991
TI  - Cell context-specific effects of the BCR-ABL oncogene monitored in hematopoietic
      progenitors.
AB  - Acute BCR-ABL expression during in vitro hematopoietic development of embryonic
      stem (ES) cells causes expansion of multipotent and myeloid progenitors with a
      concomitant reduction in differentiation toward erythroblasts. Progenitor cell
      expansion is due to a rapid, cell autonomous, suppression of programmed cell
      death with an increase in expression of the antiapoptotic molecule BCL-X(L).
      Other antiapoptotic effectors, including AKT, STAT5, and BCL-2 are not up
      regulated by BCR-ABL in this system. In addition, the proapoptotic p38 mitogen
      activated protein kinase (MAPK) pathway is suppressed by BCR-ABL expression in ES
      derived hematopoietic progenitors. Inhibition of p38 MAPK by the small molecule
      inhibitor SB203580 expanded ES-derived hematopoietic progenitors by an
      antiapoptotic mechanism and is sufficient to expand ES-derived hematopoietic
      progenitors to levels approaching 80% of that seen following BCR-ABL expression.
      In the cellular context of ES-derived hematopoietic progenitors, BCR-ABL
      expression expands cells by suppressing programmed cell death with a set of
      antiapoptotic pathways distinct from those previously reported in continuous cell
      line studies.

PMID- 12521992
TI  - Overexpression of the platelet P2X1 ion channel in transgenic mice generates a
      novel prothrombotic phenotype.
AB  - We have generated transgenic mice overexpressing the human P2X(1) ion channel in
      the megakaryocytic cell lineage. Platelets from transgenic mice exhibited a gain
      of P2X(1) ionotropic activity as determined by more prominent P2X(1)-mediated
      Ca(2+) influx and platelet shape change. P2X(1) overexpression enhanced platelet
      secretion and aggregation evoked by low doses of collagen, convulxin, or the
      thromboxane A(2) mimetic U46619. In contrast, transgenic platelet responses to
      adenosine diphosphate (ADP) or thrombin were normal. Perfusing whole blood from
      transgenic mice over collagen fibers at a shear rate of 1000 seconds(-1) resulted
      in increased P2X(1)-dependent aggregate formation and phosphatidylserine
      exposure. Platelet hyperreactivity to collagen was correlated with up-regulated
      extracellular signal-regulated kinase 2 (ERK2) phosphorylation. Accordingly, the
      MEK1/2 inhibitor U0126 potently inhibited the collagen-induced aggregation of
      transgenic platelets when stirred or when perfused over a collagen surface. In a
      viscometer, shear stress caused potent aggregation of transgenic platelets under
      conditions in which wild-type platelets did not aggregate. In an in vivo model of
      thromboembolism consisting of intravenous injection of a low dose of collagen
      plus epinephrine, transgenic mice died more readily than wild-type mice.
      Preinjection of U0126 not only fully protected transgenic mice against
      thrombosis, it also enhanced the survival of wild-type mice injected with a
      higher collagen dose. Hence, the platelet P2X(1) ion channel plays a role in
      hemostasis and thrombosis through its participation in collagen-, thromboxane
      A(2)-, and shear stress-triggered platelet responses. Activation of the ERK2
      pathway is instrumental in these processes.

PMID- 12521993
TI  - Chronic lymphocytic leukemia B cells expressing AID display dissociation between
      class switch recombination and somatic hypermutation.
AB  - In B cells, somatic hypermutation (SHM) and class switch recombination (CSR)
      depend on the activation-induced cytidine deaminase (AID) gene product, although
      the precise mode of action of AID remains unknown. Because some chronic
      lymphocytic leukemia (CLL) B cells can undergo CSR without SHM, it constitutes a
      useful model to dissect AID function. In this work, we have studied AID
      expression, the presence of mutations in the preswitch mu DNA region, CSR, and
      the SHM in 65 CLL patients. Our results demonstrate that unmutated CLL B cells
      can constitutively express AID and that AID expression is associated with the
      presence of mutations in the preswitch region and in clonally related isotype
      switched transcripts. They also demonstrate that in CLL without constitutive AID
      expression, AID induction on stimulation results in preswitch mutations and the
      CSR process. Our results show a dissociation between SHM and CSR in CLL and
      suggest that, in this disease, AID would require additional help for carrying out
      the SHM process.

PMID- 12521994
TI  - Increased sensitivity of Fancc-deficient hematopoietic cells to nitric oxide and
      evidence that this species mediates growth inhibition by cytokines.
AB  - Fanconi anemia complementation group C (Fancc)-deficient murine bone marrow
      progenitors demonstrate increased sensitivity to growth inhibition by interferon
      gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and macrophage
      inflammatory protein 1alpha (MIP-1alpha). This property has been proposed as a
      possible pathogenic factor in the marrow failure seen in Fanconi anemia.
      Supporting our hypothesis that nitric oxide (NO) production might be a common
      effector in this sensitivity, we found that cytokine-mediated growth inhibition
      of Fancc(-/-) bone marrow cells was prevented by inhibiting NO synthase activity.
      Interestingly, Fancc(-/-) hematopoietic cells also exhibited increased growth
      inhibition on exposure to 2 distinct NO-generating agents, S-nitroso-N-acetyl-D,
      L-penicillamine (SNAP) and diethylenetriamine nitric oxide adduct (DETA/NO). In
      keeping with the sensitivity of Fancc(-/-) cells to IFNgamma, inducible nitric
      oxide synthase (iNOS) levels and nitrite release were both increased following
      stimulation of Fancc(-/-) macrophages with this cytokine, either alone or in
      combination with bacterial lipopolysaccharide. Suggesting a plausible mechanism
      for the increased expression of iNOS, IFNgamma-stimulated Fancc(-/-) macrophages
      generated higher levels of phospho-Stat1, a positive regulator of inos (nos2)
      gene expression. These observations, while confined to C57BL/6 Fancc(-/-)
      hematopoietic cells, raise the possibility that nitric oxide has a role in the
      pathogenesis of Fanconi anemia.

PMID- 12521995
TI  - The quantitative assessment of body iron.
AB  - Current initiatives to reduce the high prevalence of nutritional iron deficiency
      have highlighted the need for reliable epidemiologic methods to assess iron
      status. The present report describes a method for estimating body iron based on
      the ratio of the serum transferrin receptor to serum ferritin. Analysis showed a
      single normal distribution of body iron stores in US men aged 20 to 65 years
      (mean +/- 1 SD, 9.82 +/- 2.82 mg/kg). A single normal distribution was also
      observed in pregnant Jamaican women (mean +/- 1 SD, 0.09 +/- 4.48 mg/kg).
      Distribution analysis in US women aged 20 to 45 years indicated 2 populations;
      93% of women had body iron stores averaging 5.5 +/- 3.35 mg/kg (mean +/- 1 SD),
      whereas the remaining 7% of women had a mean tissue iron deficit of 3.87 +/- 3.23
      mg/kg. Calculations of body iron in trials of iron supplementation in Jamaica and
      iron fortification in Vietnam demonstrated that the method can be used to
      calculate absorption of the added iron. Quantitative estimates of body iron
      greatly enhance the evaluation of iron status and the sensitivity of iron
      intervention trials in populations in which inflammation is uncommon or has been
      excluded by laboratory screening. The method is useful clinically for monitoring
      iron status in those who are highly susceptible to iron deficiency.

PMID- 12521996
TI  - Potentiation of dexamethasone-, paclitaxel-, and Ad-p53-induced apoptosis by Bcl
      2 antisense oligodeoxynucleotides in drug-resistant multiple myeloma cells.
AB  - Overexpression of Bcl-2 in myeloma cells results in resistance to drugs such as
      dexamethasone (DEX), adenovirus-mediated delivery of p53 (Ad-p53), and paclitaxel
      (TAX), which work through the intrinsic apoptotic pathway. Bcl-2 antisense
      oligodeoxynucleotides (Bcl-2-ASO) have been shown to induce apoptosis in cancer
      cells, as a single agent or, better, in combination with chemotherapy. We
      hypothesized that down-regulation of Bcl-2 by Bcl-2-ASO will sensitize drug
      resistant myeloma cells to undergo apoptosis. In this paper we report a detailed
      time/dose study of the effect of Bcl-2-ASO on myeloma cells with varying levels
      of Bcl-2. Treatment of myeloma cells expressing relatively low levels of Bcl-2
      with Bcl-2-ASO resulted in a substantial apoptosis concomitant with a substantial
      depletion of Bcl-2 protein. Maximal apoptosis was observed at 5 to 10 microg/mL
      Bcl-2-ASO, following 4 days of treatment. Down-regulation of Bcl-2 and apoptosis
      were time and dose dependent and were sequence specific. In these cell lines,
      apoptosis was accompanied by activation of caspase-9 and caspase-3 and by release
      of cytochrome c to the cytosol. In contrast, high Bcl-2-expressing myeloma cells
      were practically resistant to Bcl-2-ASO. Most important, however, pretreatment of
      myeloma cells expressing high levels of Bcl-2 with Bcl-2-ASO increased the extent
      of DEX-, TAX-, and Ad-p53-induced apoptosis from 10%-20% to 70%-90%. Increased
      apoptosis was accompanied by additional decrease in Bcl-2 protein. Similar
      results for down-regulation of Bcl-2 and apoptosis were obtained with freshly
      isolated myeloma cells. These data support development of clinical trials with
      combinations of Bcl-2-ASO and DEX, TAX, or Ad-p53 in the treatment of refractory
      myeloma patients.

PMID- 12521997
TI  - Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft
      rejection in allogeneic bone marrow transplant recipients.
AB  - OX40 (CD134) is expressed on activated T cells; its ligand, OX40 ligand (OX40L)
      is expressed on dendritic cells, B cells, and activated endothelial cells. To
      determine how OX40-OX40L interaction affects graft-versus-host disease (GVHD), we
      used antagonistic anti-OX40L monoclonal antibody (mAb) or OX40(-/-) donor or
      OX40L(-/-) recipient mice. Similar degrees of GVHD reduction were observed with
      each approach. Despite the fact that OX40 is up-regulated on both CD4(+) and
      CD8(+) T cells isolated during GVHD, the major effects of OX40 ligation were on
      CD4(+) and not CD8(+) T-cell-mediated alloresponses as assessed in both GVHD and
      engraftment model systems. GVHD inhibition by blockade of the OX40/OX40L pathway
      did not require CD28 signaling. Some studies have indicated OX40 is essential for
      inducing T-helper type 2 (Th2) responses. However, in vivo blockade of OX40-OX40L
      interactions reduced GVHD mortality induced by either signal transducer and
      activator of transcription-6(-/-) (Stat-6(-/-)) (Th2-defective) or Stat-4(-/-)
      (Th1-defective) major histocompatibility complex (MHC)-disparate splenocytes,
      indicating that the GVHD-ameliorating effects did not require Stat-4 or Stat-6
      signaling. Although OX40L has been reported to be expressed on activated T cells,
      no effects on GVHD were observed when OX40L(-/-) versus OX40L(+/+) T cells were
      infused in different models. These data provide insights as to the mechanisms
      responsible for OX40/OX40L regulation of GVHD.

PMID- 12521998
TI  - Marrow frequency of rat long-term repopulating cells: evidence that marrow
      hematopoietic stem cell concentration may be inversely proportional to species
      body weight.
AB  - As measured by the long-term repopulating cell (LTRC) assay, only a few
      hematopoietic stem cells (HSCs) or perhaps a single HSC are required to totally
      repopulate the lymphohematopoietic tissues of lethally irradiated mice, cats, and
      humans, raising the question as to why large mammals require more marrow cells to
      either rescue them from lethal irradiation or establish a long-term hematopoietic
      graft than do small mammals. An explanation might be that HSC marrow frequency
      across species is not constant, but decreases as species body weight increases.
      This hypothesis was tested by comparing the LTRC marrow concentration of mice to
      that of rats. Specifically, histocompatible AKR/J Thy 1.1 marrow was transferred
      to 7-Gy irradiated C3H/HeN, Thy 1.2 mice, and histocompatible Norway Black marrow
      (NBr), RT 7.2 marrow was transferred to 7-Gy irradiated RT 7.1 Lewis rats. The
      recipients were scored for successful grafts 6 to 20 weeks later. By limiting
      dilution analysis, a value of 1 LTRC/47 700 marrow cells was calculated for mice,
      but only 1 LTRC/502,000 marrow cells was calculated for rats. Viewed in the
      context of marrow grafting in larger mammals, these results suggest that species
      with greater body mass have lower marrow HSC frequency.

PMID- 12521999
TI  - Antigen-primed CD8+ T cells can mediate resistance, preventing allogeneic marrow
      engraftment in the simultaneous absence of perforin-, CD95L-, TNFR1-, and TRAIL
      dependent killing.
AB  - Engraftment failure following allogeneic bone marrow (BM) transplantation is of
      clinical concern particularly involving T-cell-depleted inoculum and
      transplantations for aplastic anemia. Immune resistance by lymphoid and natural
      killer (NK) populations with "barrier" function is well established. Major
      histocompatibility complex (MHC)-identical marrow allografts were examined to
      investigate effector pathways in non-NK-mediated resistance. Barrier function was
      examined in cytotoxic normal and deficient B6 (H-2(b)) recipients primed to donor
      minor histocompatibility antigen (MiHA) prior to BM transplantation. Host
      resistance was sensitively evaluated by colony-forming unit (CFU) assays to
      directly assess for donor progenitor cell (PC) and peripheral chimerism. B6 host
      CD8(+) T cells but not CD4(+) or NK1.1(+) cells effected rejection of primitive
      (CFU-HPP [high-proliferative potential]) and lineage-committed (CFU-IL3/GM
      [interleukin 3/granulocyte macrophage]) allogeneic donor progenitors. To address
      complementation by the cytotoxic pathways existing in singly deficient (perforin
      or FasL) recipients, cytotoxically double (perforin plus FasL) deficient (cdd)
      recipients were used. Resistance in B6-cdd recipients was comparable to that of
      wild-type B6 recipients and was also dependent on CD8(+) T cells. A "triple"
      cytotoxic deficient model, involving transplantation of TNFR1(-/-) (tumor
      necrosis factor receptor 1) progenitor grafts did not diminish the ability of B6
      cdd recipients to reject allografts. Finally, injection of anti-TRAIL (tumor
      necrosis factor-related apoptosis-inducing ligand) monoclonal antibody (mAb) in
      B6-cdd recipients also failed to inhibit rejection of TNFR1(-/-) marrow grafts.
      In total, these studies demonstrate that CD8(+) host T cells can effectively
      resist MHC-matched MiHA-mismatched donor PCs via alternative effector pathway(s)
      independent of perforin-, FasL-, TNFR-1-, and TRAIL-dependent cytotoxicity.
      Therefore, inhibition of these effector pathways in sensitized recipients is
      unlikely to result in stem cell engraftment following PC allografts.

PMID- 12522000
TI  - Chromatin immunoprecipitation (ChIP) studies indicate a role for CCAAT enhancer
      binding proteins alpha and epsilon (C/EBP alpha and C/EBP epsilon ) and CDP/cut
      in myeloid maturation-induced lactoferrin gene expression.
AB  - In vitro models of granulopoiesis involving the inducible expression of either
      CCAAT enhancer binding protein alpha (C/EBP alpha) or C/EBP epsilon in myeloid
      cells have been shown to lead to the induction of a granulocytic maturation
      program accompanied by the expression of myeloid-specific genes. Since members of
      the C/EBP family of transcription factors recognize and bind to similar DNA
      binding motifs, it has been difficult to elucidate the specific role of each of
      the C/EBP family members in eliciting myeloid gene expression. In order to
      address this issue, we focused on the expression of the lactoferrin (LF) gene. LF
      expression is transcriptionally regulated in a C/EBP-dependent manner in myeloid
      cells. Using chromatin immunoprecipitation (ChIP) analysis we demonstrate that
      C/EBP alpha binds to the LF promoter in nonexpressing cells. Upon induction of
      maturation, C/EBP epsilon binds to the LF promoter, which correlates with LF
      expression. Lack of LF expression in the acute promyelocytic leukemia cell line
      NB4, which harbors the t(15;17) translocation, cannot be correlated with aberrant
      binding at the C/EBP site in the LF promoter. It is, however, associated with the
      persistent binding of the silencer CCAAT displacement protein (CDP/cut) to the LF
      promoter in these cells. We conclude that C/EBP alpha, C/EBP epsilon, and CDP/cut
      all play definitive roles in regulating late gene expression during normal
      myeloid development.

PMID- 12522001
TI  - Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic
      interactions with paclitaxel in human myeloid leukemia cells.
AB  - Interactions between the protein kinase C (PKC) activator/down-regulator
      bryostatin 1 and paclitaxel have been examined in human myeloid leukemia cells
      (U937) and in highly paclitaxel-resistant cells ectopically expressing a Bcl-2
      phosphorylation loop-deleted protein (Delta Bcl-2). Treatment (24 hours) of wild
      type cells with paclitaxel (eg, 5 to 20 nM) in combination with 10 nM bryostatin
      1 induced a marked increase in mitochondrial damage (eg, cytochrome c and
      Smac/DIABLO [second mitochondria-derived activator of caspases/direct IAP binding
      protein with low pI] release), caspase activation, Bid cleavage, and apoptosis;
      moreover, bryostatin 1 circumvented the block to paclitaxel-induced mitochondrial
      injury and apoptosis conferred by ectopic expression of the loop-deleted protein.
      Coadministration of tumor necrosis factor (TNF) soluble receptors, or ectopic
      expression of CrmA or dominant-negative caspase-8, abrogated potentiation of
      paclitaxel-induced mitochondrial injury and apoptosis by bryostatin 1,
      implicating the extrinsic apoptotic pathway in this process. Similar events
      occurred in HL-60 leukemia cells. Potentiation of paclitaxel-induced apoptosis in
      wild-type and mutant cells by bryostatin 1 was associated with increases in TNF
      alpha mRNA and protein and was mimicked by exogenous TNF-alpha. Coadministration
      of the selective PKC inhibitor GFX (1 microM) blocked the increase in TNF-alpha
      mRNA levels and apoptosis in bryostatin 1/paclitaxel-treated cells. Lastly,
      synchronization of cells in G(2)M increased their sensitivity to TNF-alpha
      associated lethality. Collectively, these findings indicate that in U937 cells,
      bryostatin 1 promotes paclitaxel-mediated mitochondrial injury and apoptosis, and
      circumvents resistance to cell death conferred by loss of the Bcl-2
      phosphorylation domain, through the PKC-dependent induction of TNF-alpha. They
      further suggest that this process is amplified by paclitaxel-mediated arrest of
      cells in G(2)M, where they are more susceptible to TNF-alpha-induced lethality.

PMID- 12522002
TI  - Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord
      blood?

PMID- 12522003
TI  - Cytokine-mediated regulation of iron transport in human monocytic cells.
AB  - Under chronic inflammatory conditions cytokines induce a diversion of iron
      traffic, leading to hypoferremia and retention of the metal within the
      reticuloendothelial system. However, the regulatory pathways underlying these
      disturbances of iron homeostasis are poorly understood. We investigated
      transferrin receptor (TfR)-dependent and -independent iron transport mechanisms
      in cytokine-stimulated human monocytic cell lines THP-1 and U937. Combined
      treatment of cells with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS)
      reduced TfR mRNA levels, surface expression, and iron uptake, and these effects
      were reversed by interleukin-10 (IL-10), thus stimulating TfR-mediated iron
      acquisition. IFN-gamma and LPS dose-dependently increased the cellular expression
      of divalent metal transporter-1, a transmembrane transporter of ferrous iron, and
      stimulated the uptake of nontransferrin bound iron (NTBI) into cells. At the same
      time, IFN-gamma and LPS down-regulated the expression of ferroportin mRNA, a
      putative iron exporter, and decreased iron release from monocytes. Preincubation
      with IL-10 partly counteracted these effects. Our results demonstrate that the
      proinflammatory stimuli IFN-gamma and LPS increase the uptake of NTBI via
      stimulation of divalent metal transporter-1 expression and cause retention of the
      metal within monocytes by down-regulating ferroportin synthesis. Opposite, the
      anti-inflammatory cytokine IL-10 stimulates TfR-mediated iron uptake into
      activated monocytes. The regulation of iron transport by cytokines is a key
      mechanism in the pathogenesis of anemia of chronic disease and a promising target
      for therapeutic intervention.

PMID- 12522004
TI  - Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic
      leukemia cells but not in T lymphocytes.
AB  - Acadesine, 5-aminoimidazole-4-carboxamide (AICA) riboside, induced apoptosis in B
      cell chronic lymphocytic leukemia (B-CLL) cells in all samples tested (n = 70).
      The half-maximal effective concentration (EC(50)) for B-CLL cells was 380 +/- 60
      microM (n = 5). The caspase inhibitor Z-VAD.fmk completely blocked acadesine
      induced apoptosis, which involved the activation of caspase-3, -8, and -9 and
      cytochrome c release. Incubation of B-CLL cells with acadesine induced the
      phosphorylation of adenosine monophosphate-activated protein kinase (AMPK),
      indicating that it is activated by acadesine. Nitrobenzylthioinosine (NBTI), a
      nucleoside transport inhibitor, 5-iodotubercidin, an inhibitor of adenosine
      kinase, and adenosine completely inhibited acadesine-induced apoptosis and AMPK
      phosphorylation, demonstrating that incorporation of acadesine into the cell and
      its subsequent phosphorylation to AICA ribotide (ZMP) are necessary to induce
      apoptosis. Inhibitors of protein kinase A and mitogen-activated protein kinases
      did not protect from acadesine-induced apoptosis in B-CLL cells. Moreover,
      acadesine had no effect on p53 levels or phosphorylation, suggesting a p53
      independent mechanism in apoptosis triggering. Normal B lymphocytes were as
      sensitive as B-CLL cells to acadesine-induced apoptosis. However, T cells from
      patients with B-CLL were only slightly affected by acadesine at doses up to 4 mM.
      AMPK phosphorylation did not occur in T cells treated with acadesine.
      Intracellular levels of ZMP were higher in B-CLL cells than in T cells when both
      were treated with 0.5 mM acadesine, suggesting that ZMP accumulation is necessary
      to activate AMPK and induce apoptosis. These results suggest a new pathway
      involving AMPK in the control of apoptosis in B-CLL cells and raise the
      possibility of using acadesine in B-CLL treatment.

PMID- 12522005
TI  - Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2
      induced fos gene transcription.
AB  - Prostaglandin E(2) (PGE(2)) is the predominant eicosanoid product released by
      macrophages at the site of inflammation. Binding of PGE(2) to its cognate 7
      transmembrane-spanning G protein-coupled receptors (GPCRs) activates signaling
      pathways, leading to the synthesis of the Fos transcription factor. Because the
      Ste20 serine/threonine protein kinase (S/TPK) is a critical signal transducer for
      the G protein-coupled pheromone receptor in Saccharomyces cerevisiae, we
      postulated that the PGE(2) GPCRs may activate one of the Ste20 mammalian
      orthologs. We demonstrate here that the catalytic activity of a hematopoietic
      cell-restricted, Ste20-related S/TPK, HPK1, is positively regulated by exposure
      to physiological concentrations of PGE(2). Furthermore, ectopic expression
      studies implicated HPK1 as a negative regulator of PGE(2)-induced transcription
      of the fos gene. Our data suggest that PGE(2)-induced activation of HPK1 may
      represent a novel negative regulatory pathway capable of modulating PGE(2)
      mediated gene transcription.

PMID- 12522006
TI  - Reciprocal effects of C/EBPalpha and PKCdelta on JunB expression and monocytic
      differentiation depend upon the C/EBPalpha basic region.
AB  - Monocytic differentiation of 32DPKCdelta cells in response to activation of
      protein kinase C delta (PKCdelta) by phorbol 12-myristate 13-acetate (PMA) was
      inhibited by exogenous CCAAT/enhancer binding protein alpha-estradiol receptor
      (C/EBPalpha-ER), which impeded morphologic maturation and induction of
      macrosialin mRNA. Inhibition of monopoiesis was also evident in 32DPKCdelta
      subclones expressing C/EBPalphaLeu12Val-ER, which cannot dimerize or bind DNA
      because of mutation of the leucine zipper, C/EBPalphaGZ-ER, in which the leucine
      zipper has been replaced by the GCN4 zipper, or C/EBPalphaDelta3-8-ER, lacking
      the C/EBPalpha transactivation domains. In contrast, C/EBPalphaBR3-ER, containing
      a mutant basic region, did not inhibit monocytic differentiation. C/EBPalpha-ER
      strongly inhibited endogenous AP-1 DNA-binding. Supershift analysis revealed that
      the major AP-1 complex contains JunB. Activation of C/EBPalpha-ER specifically
      reduced endogenous JunB RNA and protein and exogenous JunB levels without
      affecting endogenous or exogenous c-Jun. The stability of PMA-induced JunB was
      not affected. Thus, C/EBPalpha-ER suppresses both JunB transcription and
      posttranscriptional protein generation or induction. PU.1 levels and activity
      were increased. The Leu12Val, GZ, and Delta3-8 mutants also inhibited JunB
      expression, whereas the BR3 mutant was ineffective, indicating that inhibition of
      JunB expression and monocytic differentiation by C/EBPalpha-ER depends upon an
      interaction mediated by its basic region. Exogenous JunB restored AP-1 DNA
      binding but did not prevent inhibition of macrosialin expression by C/EBPalpha
      ER, indicating that JunB is not the only target relevant to inhibition of
      monopoiesis by C/EBPalpha.

PMID- 12522007
TI  - Iron transport by Nramp2/DMT1: pH regulation of transport by 2 histidines in
      transmembrane domain 6.
AB  - Mutations at natural resistance-associated macrophage protein 1 (Nramp1) impair
      phagocyte function and cause susceptibility to infections while mutations at
      Nramp2 (divalent metal transporter 1 [DMT1]) affect iron homeostasis and cause
      severe microcytic anemia. Structure-function relationships in the Nramp
      superfamily were studied by mutagenesis, followed by functional characterization
      in yeast and in mammalian cells. These studies identify 3 negatively charged and
      highly conserved residues in transmembrane domains (TM) 1, 4, and 7 as essential
      for cation transport by Nramp2/DMT1. The introduction of a charged residue
      (Gly185Arg) in TM4 found in the naturally occurring microcytic anemia mk (mouse)
      and Belgrade (rat) mutants is shown to cause a partial or complete loss of
      function in mammalian and yeast cells, respectively. A pair of mutation-sensitive
      and highly conserved histidines (His267, His272) was identified in TM6.
      Surprisingly, inactive His267 and His272 mutants could be rescued by lowering the
      pH of the transport assay. This indicates that His267/His272 are not directly
      involved in metal binding but, rather, play an important role in pH regulation of
      metal transport by Nramp proteins.

PMID- 12522008
TI  - Elevated plasma factor VIII in a mouse model of low-density lipoprotein receptor
      related protein deficiency.
AB  - It has been established that low-density lipoprotein receptor-related protein
      (LRP) is involved in the cellular uptake and degradation of coagulation factor
      VIII (FVIII) in vitro. To address the physiologic role of LRP in regulating
      plasma FVIII in vivo, we used cre/loxP-mediated conditional LRP- deficient mice
      (MX1cre(+)LRP(flox/flox)). Upon inactivation of the LRP gene,
      MX1cre(+)LRP(flox/flox) mice had significantly higher plasma FVIII as compared
      with control LRP(flox/flox) mice (3.4 and 2.0 U/mL, respectively; P <.001).
      Elevated plasma FVIII levels in MX1cre(+)LRP(flox/flox) mice coincided with
      increased plasma von Willebrand factor (VWF) (2.0 and 1.6 U/mL for
      MX1cre(+)LRP(flox/flox) and control LRP(flox/flox) mice, respectively; P <.05).
      Elevation of plasma FVIII and VWF persisted for at least 6 weeks after
      inactivation of the LRP gene. Upon comparing plasma FVIII and VWF in individual
      mice, we observed an increase of the FVIII/VWF ratio in MX1cre(+)LRP(flox/flox)
      mice as compared with control LRP(flox/flox) mice. Administration of either a
      vasopressin analog or an endotoxin resulted in increased plasma VWF, but not
      FVIII. In clearance experiments, MX1cre(+)LRP(flox/flox) mice displayed a 1.5
      fold prolongation of FVIII mean residence time. Adenovirus-mediated
      overexpression of the 39-kDa receptor-associated protein (RAP) in normal mice
      resulted in a 3.5-fold increase of plasma FVIII. These data confirm that the
      regulation of plasma FVIII in vivo involves a RAP-sensitive mechanism.
      Surprisingly, plasma FVIII in MX1cre(+)LRP(flox/flox) mice increased 2-fold after
      RAP gene transfer. We propose that RAP-sensitive determinants other than hepatic
      LRP contribute to the regulation of plasma FVIII in vivo.

PMID- 12522009
TI  - Experience with alemtuzumab plus rituximab in patients with relapsed and
      refractory lymphoid malignancies.
AB  - We explored the safety and efficacy of rituximab plus alemtuzumab in patients
      with relapsed or refractory lymphoid malignancies. Forty-eight patients were
      treated and were assessable for response (32 with chronic lymphocytic leukemia
      [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell
      leukemia/lymphoma, 2 with Richter transformation). The overall response rate was
      52% (complete remission, 8%; nodular partial response, 4%; partial response,
      40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time
      to progression was 6 months (range, 1-20 months); median survival, 11 months (11+
      months for responders vs 6 months for nonresponders). Most toxicities were grade
      2 or lower and infusion-related. Infections occurred in 52% of the patients.
      Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients,
      but only 15% were symptomatic and required therapy. The combination of rituximab
      and alemtuzumab is feasible, has an acceptable safety profile, and has clinical
      activity with a short course in a group of patients with poor prognoses.

PMID- 12522010
TI  - Gene expression profile in human leukocytes.
AB  - Leukocytes are classified as myelocytic or lymphocytic, and each class of
      leukocytes consists of several types of cells that have different phenotypes and
      different roles. To define the gene expression in these cells, we have performed
      serial analysis of gene expression (SAGE) using human leukocytes and have
      provided the gene database for these cells not only at the resting stage but also
      at the activated stage. A total of 709,990 tags from 17 libraries were analyzed
      for the manifestation of gene expression profiles in various types of human
      leukocytes. Types of leukocytes analyzed were as follows: peripheral blood
      monocytes, colony-stimulating factor-induced macrophages, monocyte-derived
      immature dendritic cells, mature/activated dendritic cells, granulocytes, natural
      killer (NK) cells, resting B cells, activated B cells, naive T cells, CCR4(-)
      memory T cells (resting T(H)1 cells), CCR4(+) memory T cells (resting T(H)2
      cells), activated T(H)1 cells, and activated T(H)2 cells. Among 38,961 distinct
      tags that appeared more than once in the combined total libraries, 27,323 tags
      were found to represent unique genes in certain type(s) of leukocytes. Using
      probability (P) and hierarchical clustering analysis, we identified the genes
      selectively expressed in each type of leukocytes. Identification of the genes
      specifically expressed in different types of leukocytes provides not only a novel
      molecular signature to define different subsets of resting and activated cells
      but also contributes to further understanding of the biologic function of
      leukocytes in the host defense system.

PMID- 12522011
TI  - Role of the intracellular domains of GPIb in controlling the adhesive properties
      of the platelet GPIb/V/IX complex.
AB  - Glycoprotein (GP) Ib/V/IX complex-dependent platelet adhesion to von Willebrand
      factor (VWF) is supported by the 45-kd N-terminal extracellular domain of the
      GPIb alpha subunit. Recent results with an adhesion blocking antibody (RAM.1)
      against GPIb beta, which is disulfide linked to GPIb alpha, have suggested a
      novel function of this subunit in regulating VWF-mediated platelet adhesion,
      possibly involving its intracellular face. A putative cooperation between the
      GPIb alpha and GPIb beta cytoplasmic domains was investigated by measuring the
      adhesion under flow to immobilized VWF of K562 and Chinese hamster ovary (CHO)
      cells transfected with GPIb/(V)/IX containing mutations in this region. Adhesion
      of cells carrying a glycine substitution of the GPIb beta Ser166 phosphorylation
      site was 50% lower than normal and became insensitive to inhibition by RAM.1. In
      contrast, forskolin or PGE(1) treatment increased both the phosphorylation of
      GPIb beta and adhesion of control cells, both effects being reversed by RAM.1,
      but had no influence on cells expressing the Ser166Gly mutation. A role of the
      GPIb alpha intracellular domain was also apparent as the VWF-dependent adhesion
      of cells containing deletions of the entire (Delta 518-610) or portions (Delta
      535-568, Delta 569-610) of the GPIb alpha cytoplasmic tail was insensitive to
      RAM.1 inhibition. Cells carrying progressive 11 amino acid deletions spanning the
      GPIb alpha 535-590 region were equally unresponsive to RAM.1, with the exception
      of those containing GPIb alpha Delta 569-579, which behaved like control cells.
      These findings support a role of the GPIb beta intracellular domain in
      controlling the adhesive properties of the GPIb/V/IX complex through
      phosphorylation of GPIb beta Ser166 and point to the existence of cross-talk
      between the GPIb beta and GPIb alpha intracellular domains.

PMID- 12522012
TI  - Alternative 5' exons and differential splicing regulate expression of protein
      4.1R isoforms with distinct N-termini.
AB  - Among the alternative pre-mRNA splicing events that characterize protein 4.1R
      gene expression, one involving exon 2' plays a critical role in regulating
      translation initiation and N-terminal protein structure. Exon 2' encompasses
      translation initiation site AUG1 and is located between alternative splice
      acceptor sites at the 5' end of exon 2; its inclusion or exclusion from mature
      4.1R mRNA regulates expression of longer or shorter isoforms of 4.1R protein,
      respectively. The current study reports unexpected complexity in the 5' region of
      the 4.1R gene that directly affects alternative splicing of exon 2'. Identified
      far upstream of exon 2 in both mouse and human genomes were 3 mutually exclusive
      alternative 5' exons, designated 1A, 1B, and 1C; all 3 are associated with strong
      transcriptional promoters in the flanking genomic sequence. Importantly, exons 1A
      and 1B splice differentially with respect to exon 2', generating transcripts with
      different 5' ends and distinct N-terminal protein coding capacity. Exon 1A-type
      transcripts splice so as to exclude exon 2' and therefore utilize the downstream
      AUG2 for translation of 80-kDa 4.1R protein, whereas exon 1B transcripts include
      exon 2' and initiate at AUG1 to synthesize 135-kDa isoforms. RNA blot analyses
      revealed that 1A transcripts increase in abundance in late erythroblasts,
      consistent with the previously demonstrated up-regulation of 80-kDa 4.1R during
      terminal erythroid differentiation. Together, these results suggest that
      synthesis of structurally distinct 4.1R protein isoforms in various cell types is
      regulated by a novel mechanism requiring coordination between upstream
      transcription initiation events and downstream alternative splicing events.

PMID- 12522013
TI  - Gamma-delta T-cell phenotype is associated with significantly decreased survival
      in cutaneous T-cell lymphoma.
AB  - The importance of alpha beta versus gamma delta T-cell subset antigen expression
      in the classification of peripheral T-cell lymphomas is still unclear. The
      objective of this study was to investigate the prognostic value of T-cell
      receptor-delta 1 (TCR delta 1) expression in primary cutaneous T-cell lymphomas.
      TCR delta 1 cellular expression was assessed in skin biopsy specimens of 104
      individuals with cutaneous T-cell lymphoma by immunohistochemistry. Both
      univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were
      conducted to determine which variables (T-cell subtype, hemophagocytosis,
      histologic profile, age, sex, and adenopathy) were significantly associated with
      survival. Univariate analysis indicated that there was a statistically
      significant difference in survival between the patients with alpha beta cutaneous
      T-cell lymphoma and patients with gamma delta cutaneous T-cell lymphoma (P
      <.0001). There was also a statistically significant decrease in survival among
      patients who had subcutaneous involvement compared with patients who had
      epidermotropic and/or dermal involvement (P <.0001). Cox model analysis indicated
      that TCR delta 1 expression was the factor that was most closely associated with
      decreased survival (P <.0001). Among those patients with cutaneous gamma delta T
      cell lymphoma (n = 33), there was a trend for decreased survival for patients who
      had histologic evidence of subcutaneous fat involvement in comparison with
      patients who had epidermotropic or dermal patterns of infiltration (P =.067). No
      other prognostic factors were identified as having a notable association with
      outcome in this subgroup. TCR delta 1 expression in primary cutaneous lymphomas
      is an independent prognostic factor associated with decreased survival.

PMID- 12522014
TI  - Src and phosphatidylinositol 3-kinase mediate soluble E-selectin-induced
      angiogenesis.
AB  - Angiogenesis plays an important role in a variety of pathophysiologic processes,
      including tumor growth and rheumatoid arthritis. We have previously shown that
      soluble E-selectin (sE-selectin) is an important angiogenic mediator. However,
      the mechanism by which sE-selectin mediates angiogenesis is still unknown. In
      this study, we show that sE-selectin is a potent mediator of human dermal
      microvascular endothelial cell (HMVEC) chemotaxis, which is predominantly
      mediated through the Src and the phosphatidylinositiol 3-kinase (PI3K) pathways.
      Further, sE-selectin induced a 2.2-fold increase in HMVEC tube formation in the
      Matrigel in vitro assay. HMVECs pretreated with the Src inhibitor (PP2) and the
      PI3K inhibitor (LY294002) or transfected with Src antisense oligonucleotides or
      Akt dominant-negative mutants significantly inhibited sE-selectin-mediated HMVEC
      tube formation. In contrast, HMVECs transfected with an extracellular signal
      related kinase 1/2 (ERK1/2) mutant or pretreated with the mitogen-activated
      protein kinase (MAPK) inhibitor PD98059 failed to show sE-selectin-mediated HMVEC
      tube formation. Similarly, in the Matrigel-plug in vivo assay, sE-selectin
      induced a 2.2-fold increase in blood vessel formation, which was significantly
      inhibited by PP2 and LY294002 but not by PD98059. sE-selectin induced a marked
      increase in Src, ERK1/2, and PI3K phosphorylation. PI3K and ERK1/2
      phosphorylation was significantly inhibited by PP2, thereby suggesting that both
      of these pathways may be activated via Src kinase. Even though the ERK1/2 pathway
      was activated by sE-selectin in HMVECs, it seems not to be essential for sE
      selectin-mediated angiogenesis. Taken together, our data clearly show that sE
      selectin-induced angiogenesis is predominantly mediated through the Src-PI3K
      pathway.

PMID- 12522015
TI  - Invited commentary: the potential for monitoring of fecundity and the remaining
      challenges.
AB  - In the epidemiologic study of reproductive capacity, the assessment of fecundity
      as a functional measure is complementary to approaches that focus on biomedical
      mechanisms and/or that use biomarkers such as semen quality. More research is
      needed on time trends, spatial patterns, and particular groups, especially those
      exposed to potentially toxic agents. Although specific research projects will
      always be important, much could be gained by general population surveillance,
      which could be introduced into existing multipurpose surveys and repeated
      periodically. The core measurement would be time to pregnancy, which can be
      carried out using a short, acceptable questionnaire that has good validity at the
      group level. This should be accompanied by questions on time periods of
      unprotected intercourse that do not end with conception, to avoid bias resulting
      from exclusion of relatively infertile couples. Information is also required on
      contraceptive failures, recent contraceptive use, and other covariates and
      possibly on behavioral variables, such as the degree of planning and persistence
      in trying to conceive, and couples' knowledge of fertile days of the menstrual
      cycle. Existing statistical methods can deal with possible biases due to
      "accidental" pregnancies and the effects of fertility treatment. Further
      methodological work is needed to avoid or measure more subtle biases, for
      example, to determine the best way to deal with pregnancies occurring to couples
      whose approach to family formation is relaxed, for whom the concept of "pregnancy
      planning" does not apply.

PMID- 12522016
TI  - Invited commentary: monitoring fecundity over time--if we do it, then let's do it
      right.
AB  - A number of investigators have pointed to the possibility of a secular decline in
      human fecundity due to changes in sperm concentration. It is unlikely that any
      historical trends will be definitively quantified, but a good case can be made
      for more precise monitoring of this phenomenon in the future. Such monitoring
      would be justified on the grounds of the importance of early detection of
      environmental effects on the capacity of humans to reproduce. Establishing a
      surveillance system that will be sensitive enough to detect changes in fecundity
      over time is, however, a challenging enterprise because of methodological
      concerns. It may be impossible to obtain a quality of design that will pick up
      subtle changes in fecundity.

PMID- 12522017
TI  - Socioeconomic inequalities in depression: a meta-analysis.
AB  - Low socioeconomic status (SES) is generally associated with high psychiatric
      morbidity, more disability, and poorer access to health care. Among psychiatric
      disorders, depression exhibits a more controversial association with SES. The
      authors carried out a meta-analysis to evaluate the magnitude, shape, and
      modifiers of such an association. The search found 51 prevalence studies, five
      incidence studies, and four persistence studies meeting the criteria. A random
      effects model was applied to the odds ratio of the lowest SES group compared with
      the highest, and meta-regression was used to assess the dose-response relation
      and the influence of covariates. Results indicated that low-SES individuals had
      higher odds of being depressed (odds ratio = 1.81, p < 0.001), but the odds of a
      new episode (odds ratio = 1.24, p = 0.004) were lower than the odds of persisting
      depression (odds ratio = 2.06, p < 0.001). A dose-response relation was observed
      for education and income. Socioeconomic inequality in depression is heterogeneous
      and varies according to the way psychiatric disorder is measured, to the
      definition and measurement of SES, and to contextual features such as region and
      time. Nonetheless, the authors found compelling evidence for socioeconomic
      inequality in depression. Strategies for tackling inequality in depression are
      needed, especially in relation to the course of the disorder.

PMID- 12522018
TI  - Body mass index at age 18 years and during adult life and ovarian cancer risk.
AB  - During the years 1994-1999, a nationwide ovarian cancer case-control study was
      conducted in Israel. The present analysis addresses the question: Is epithelial
      ovarian cancer associated with body mass index at age 18 years and/or with weight
      changes in body mass index between adolescence and adult life? The study is based
      on 1,269 women with epithelial ovarian cancer and 2,111 matched controls. A
      significant decrease in risk of ovarian cancer was observed with parity, oral
      contraceptive use, and postmenopausal status. A significant increase in risk with
      family history of ovarian/breast cancer was also found. No significant
      association with age at menarche or infertility was found. For body mass index at
      age 18 years, the odds ratio of the highest versus lowest body mass index
      quartile was 1.42 (95% confidence interval: 1.08, 1.85) and after adjusting for
      confounders was 1.54 (95% confidence interval: 1.17, 2.02). However, no
      statistically significant risk associated with change in weight from age 18 years
      to adult life was found. The authors conclude that, in their population, body
      mass index at age 18 years is an independent risk factor for ovarian cancer.

PMID- 12522019
TI  - Case-control study of physical activity and breast cancer risk among
      premenopausal women in Germany.
AB  - Important aspects of the recognized inverse relation between physical activity
      and breast cancer risk are still under discussion. Data on physical activity from
      sports, occupational activity, household tasks, walking, and cycling by reported
      frequency, duration, and intensity during adolescence and young adulthood were
      collected in 1999-2000 from 360 premenopausal breast cancer cases and 886
      controls who had previously participated in a German population-based case
      control study. In multivariate conditional logistic regression, no association
      between total physical activity and premenopausal breast cancer was found in two
      age periods. For women who were active during both periods, the adjusted odds
      ratio was 0.83 (95% confidence interval: 0.60, 1.14). When both age periods were
      combined, higher quartiles of total physical activity compared with the lowest
      quartile showed adjusted odds ratios of 0.97, 0.68, and 0.94. Only the effect of
      moderately high physical activity was statistically significant. Analyses by type
      of activity revealed significant protective effects for women who reported the
      highest levels of cycling activities (adjusted odds ratio = 0.66, 95% confidence
      interval: 0.45, 0.97). These data do not suggest an inverse monotonic association
      between total physical activity and breast cancer risk in premenopausal women.
      The study prevalence of cycling and walking for transportation demonstrated that
      national habits need consideration in the exposure assessment.

PMID- 12522020
TI  - Association of alcohol-related laws with deaths due to motor vehicle and
      motorcycle crashes in the United States, 1980-1997.
AB  - The authors compared US motor vehicle and motorcycle mortality rates during
      periods when each of several alcohol-related laws were in effect with mortality
      rates during other periods. During the period 1980-1997, there were 792,184
      deaths due to motor vehicle crashes and 63,052 deaths due to motorcycle crashes.
      An estimated 26% and 49% of these fatalities, respectively, were attributable to
      alcohol use. The incidence of alcohol-related mortality in motor vehicle crashes
      was lower when laws specifying a blood alcohol concentration of 0.08 g/dl per se
      (laws stating that it is a criminal offense to drive with a blood alcohol
      concentration above the state's legal limit) were in effect (adjusted rate ratio
      (RR) = 0.86, 95% confidence interval (CI): 0.83, 0.88). For motorcycle deaths,
      the adjusted rate ratio was 0.87 (95% CI: 0.79, 0.95). The incidence of alcohol
      related mortality in motor vehicle crashes was also lower during periods when two
      other types of laws were in effect: zero tolerance laws (adjusted RR = 0.88, 95%
      CI: 0.86, 0.90) and administrative license revocation laws (adjusted RR = 0.95,
      95% CI: 0.93, 0.98). Overall motorcycle mortality was lower when administrative
      license revocation laws were in effect (adjusted RR = 0.95, 95% CI: 0.92, 0.98).

PMID- 12522021
TI  - Post-traumatic stress disorder and chronic fatigue syndrome-like illness among
      Gulf War veterans: a population-based survey of 30,000 veterans.
AB  - The authors estimated the prevalence of post-traumatic stress disorder (PTSD) and
      illness resembling chronic fatigue syndrome (CFS) in the entire population of
      Gulf War and non-Gulf-War veterans. They also evaluated the relation between the
      extent of deployment-related stress and the risk of either PTSD or CFS. In 1995
      1997, the authors conducted a health survey in which these two symptom-based
      medical diagnoses in a population-based sample of 15,000 Gulf War veterans
      representing four military branches and three unit components (active, reserve,
      and National Guard) were compared with those of 15,000 non-Gulf veteran controls.
      Gulf War veterans, compared with non-Gulf veteran controls, reported
      significantly higher rates of PTSD (adjusted odds ratio = 3.1, 95% confidence
      interval: 2.7, 3.4) and CFS (adjusted odds ratio = 4.8, 95% confidence interval:
      3.9, 5.9). The prevalence of PTSD increased monotonically across six levels of
      deployment-related stress intensity (test for trend: p < 0.01), while the
      prevalence of CFS rose only at the low end of the stress spectrum. While
      deployment-related stress could account for the higher risks of both PTSD and
      CFS, additional factor(s) unique to the Gulf environment may have contributed to
      the risk of CFS among Gulf War veterans.

PMID- 12522022
TI  - Amyotrophic lateral sclerosis and parkinsonism-dementia complex of Guam: changing
      incidence rates during the past 60 years.
AB  - In the 1950s, the incidence of amyotrophic lateral sclerosis (ALS, or Lytico) and
      parkinsonism-dementia complex (PDC, or Bodig) on the island of Guam was much
      higher than anywhere else in the world. From the late 1960s to the early 1980s,
      the incidence of both disorders has decreased. The objective of the present study
      was to ascertain whether the decreasing incidence continued until the end of the
      century (1999). The average annual incidence of ALS and PDC was calculated for
      each 5-year period from 1940 to 1999, utilizing registration records of all ALS
      and PDC cases on Guam during that period. The results of this study confirmed
      that the incidence of ALS declined steadily during the past 40 years. The
      incidence of PDC also declined until the late 1980s but, unlike ALS, showed a
      slight increase from 1980 to 1999. The rapid decrease in incidence is not likely
      to be due to genetic factors. Instead, it is most likely to be the results of
      radical socioeconomic, ethnographic, and ecologic changes brought about by the
      rapid westernization of Guam.

PMID- 12522023
TI  - Risk analysis of aseptic meningitis after measles-mumps-rubella vaccination in
      Korean children by using a case-crossover design.
AB  - Epidemiologic study of a vaccine's adverse events is not easy; so many countries
      have no reliable data. Vaccines containing the Urabe or Hoshino strain have been
      withdrawn from use in several countries. However, the data are not strong enough
      to form the basis of a recommendation not to use specific strains. The authors
      used a case-crossover design to estimate the relative risk of aseptic meningitis
      in children after receiving the measles-mumps-rubella vaccine in Korea. Study
      subjects were hospitalized children aged 8-36 months who had aseptic meningitis
      in 1998. Cases were confirmed by hospital chart reviews using previously defined
      criteria. Through a telephone survey, the authors obtained vaccination date and
      place information from parents' vaccination records. Study results showed that no
      significant risk was associated with the Jeryl Lynn or Rubini strain of the
      vaccine (relative risk = 0.6, 95% confidence interval (CI): 0.18, 1.97). For the
      Urabe or Hoshino strain, the relative risk was 5.5 (95% CI: 2.6, 11.8); the risk
      increased in the third week after vaccination (relative risk = 15.6, 95% CI: 5.9,
      41.2) and was elevated until the sixth week. The case-crossover design was useful
      in confirming the risk of acute adverse events after receiving vaccines.

PMID- 12522024
TI  - Effects of acute diarrhea on linear growth in Peruvian children.
AB  - Linear growth retardation during childhood is a determinant of short stature and
      impaired capacities in adults of developing countries. To study the effect of
      diarrhea on height during childhood, the authors followed a birth cohort of 224
      Peruvian children for 35 months with records of daily diarrhea and monthly
      anthropometry. This study was conducted from April 1995 to December 1998. At 24
      months of age, study children were 2.5 cm shorter than the US National Center for
      Health Statistics/World Health Organization growth reference. A diarrheal
      prevalence of 2.3% in the first 24 months of life explained 2-27% of this growth
      deficit. There was a 2-month delay before the effects of diarrhea on height
      became manifest. Height deficits were proportional to diarrheal prevalence. For
      example, children ill with diarrhea 10% of the time during the first 24 months
      were 1.5 cm shorter than children who never had diarrhea. In addition, the
      adverse effects of diarrhea on height varied by age. Diarrhea during the first 6
      months of life resulted in long-term height deficits that were likely to be
      permanent. In contrast, diarrhea after 6 months of age showed transient effects.
      Study results indicate that diarrhea control, especially during the first 6
      months of life, is likely to improve linear growth in Peruvian children.

PMID- 12522025
TI  - Hospital or population controls for case-control studies of severe childhood
      diseases?
AB  - There are few empirical data to determine which control group seems best in a
      case-control study for a severe disease: population controls or hospital
      controls. The author conducted a case-control study of leukemia in children using
      two control groups, population and hospital controls (cancers other than leukemia
      and severe blood diseases), between 1980 and 1993 in Quebec, Canada. Maternal,
      paternal, and child factors not known to be associated with leukemia as well as
      factors possibly associated were selected for analysis. Most factors were taken
      directly from parental interviews, but two factors related to parental
      occupational exposures were blindly coded by chemists. Hospital and population
      controls were compared using odds ratios estimated from logistic regression.
      Cases were compared with both types of controls with the same statistical method.
      Prevalence data from ongoing population surveys were compared with reported
      prevalence in controls. From the former comparisons and the distribution of
      socioeconomic variables, results suggested that study groups came from the same
      base population. Nevertheless, reported and coded exposures among hospital
      controls were closer to those of cases than to those of population controls.
      Although substantially different for only one factor, inferences using hospital
      controls in comparison with population controls resulted in odds ratios closer to
      the null value.

PMID- 12522026
TI  - A snapshot of pulmonary medicine at the turn of the century: the American
      Thoracic Society membership.
AB  - To describe the characteristics of the American Thoracic Society, the Membership
      Committee developed a survey to assess demographics, training, professional
      activities, and needs of a diverse membership with a growing international
      segment. It also provided an opportunity to determine how the Society reflects
      the current state of pulmonary medicine in the United States. A self-administered
      survey was mailed to active members. Of responding members, 80% reside in the
      United States or Canada; the remainder come from 90 different countries. The
      majority of North American respondents (79%) were white, non-Hispanic. Seventeen
      percent of respondents were female. Female respondents were younger, with a mean
      age of 42 years, compared with 47 years for males. Sixty-five percent of
      respondents identified clinical practice, 20% research, and 5% teaching as their
      major activity. More women (33%) than men (22%) identified themselves as
      researchers. The majority of respondents (69%) have a medical school faculty
      affiliation. The American Thoracic Society represents a global organization with
      diverse clinical expertise and scientific interests. The majority of respondents
      are clinicians; however, the membership has a strong academic bent with most
      reporting academic affiliation, and describing teaching as a secondary activity.

PMID- 12522027
TI  - Nasal epithelium potential difference at high altitude (4,559 m): evidence for
      secretion.
AB  - Hypoxia inhibits activity and expression of ion transport proteins of cultured
      lung alveolar epithelial cells. Here we tested, whether in vivo hypoxia at high
      altitude (4,559 m) also inhibits lung ion transport. Transepithelial nasal
      potentials (NP) were determined as a surrogate measure of lung ion transport
      activity before and during the stay at altitude. In normoxia, total NP was
      approximately 20% higher in control subjects than in susceptibles to high
      altitude pulmonary edema, but there was no difference between groups in amiloride
      inhibitable NPs. At high altitude total NP increased 250% in both groups, whereas
      amiloride-sensitive NP decreased in control subjects only (-80%), and the
      chloride ion (Cl-)-sensitive portion of NP almost doubled. Because many
      mountaineers suffer from nasal dryness at high altitude, a control study was
      performed in normobaric hypoxia (12% oxygen, 6 hours) at a controlled humidity of
      50%. In this study, no change in total NP or its amiloride- and Cl-sensitive
      portions was observed. The increased Cl- secretion at high altitude but no such
      change in normobaric hypoxia suggests that nasal dryness may stimulate local
      active Cl- and fluid secretion in the upper respiratory tract. It is therefore
      uncertain whether similar changes also occur at the alveolar epithelium.

PMID- 12522028
TI  - Methylprednisolone causes matrix metalloproteinase-dependent emphysema in adult
      rats.
AB  - Previous investigations have shown that corticosteroids affect the development
      and maturation of the developing lung in utero and in neonatal animals. Systemic
      corticosteroids are routinely used for the treatment of acute exacerbations of
      chronic obstructive pulmonary disease, and inhaled corticosteroids are more
      frequently being prescribed for the long-term treatment of patients with chronic
      obstructive pulmonary disease. Because corticosteroids can affect matrix
      metalloproteinases and because the concept of protease/antiprotease imbalance is
      an important concept regarding the pathogenesis of emphysema, we examined the
      effects of chronic steroid treatment on lung structure in adult rats. Rats
      treated with 2 mg/kg of methylprednisolone daily for 1, 2, or 4 weeks had an
      increased mean linear intercept and a decrease of the surface-volume ratio when
      compared with age-matched control animals, and the animals showed increased
      matrix metalloproteinase-9 activity in their lungs on zymography. Rats treated
      concomitantly with methylprednisolone and a broad-spectrum matrix
      metalloproteinase inhibitor (GM6001) did not develop emphysema. We conclude that
      systemic treatment of adult rats with the antiinflammatory steroid
      methylprednisolone increases the activity of matrix metalloproteinases in the
      lung and causes emphysema.

PMID- 12522029
TI  - Aldehydes in exhaled breath condensate of patients with chronic obstructive
      pulmonary disease.
AB  - The aims of the present study were (1) to evaluate whether individual aldehydes
      resulting from lipid peroxidation can be measured in exhaled breath condensate,
      (2) to assess the influence of sampling procedures on aldehyde concentrations,
      and (3) to compare aldehyde levels of patients with stable, moderate to severe,
      chronic obstructive pulmonary disease with those of smoking and nonsmoking
      control subjects. Aldehydes (malondialdehyde, hexanal, heptanal, and nonanal)
      were measured by liquid chromatography-tandem mass spectrometry in all samples
      and overlapping results were obtained by different sampling procedures.
      Malondialdehyde (57.2 +/- 2.4 nmol/L), hexanal (63.5 +/- 4.4 nmol/L), and
      heptanal (26.6 +/- 3.9 nmol/L) were increased in patients as compared with
      nonsmoking control subjects (17.7 +/- 5.5 nmol/L, p < 0.0001; 14.2 +/- 3.5
      nmol/L, p = 0.004; and 18.7 +/- 0.9 nmol/L, p = 0.002, respectively). Only
      malondialdehyde was increased in patients compared with smoking control subjects
      (35.6 +/- 4.0 nmol/L, p = 0.0007). In conclusion, different classes of aldehydes
      were identified in exhaled breath condensate of humans. Whereas all aldehydes but
      nonanal were lower in control subjects as compared with other groups, only
      malondialdehyde distinguished smoking control subjects from patients with chronic
      obstructive pulmonary disease and could be envisaged as a biomarker potentially
      useful to monitor the disease and its response to therapy.

PMID- 12522030
TI  - Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation
      via tumor necrosis factor-alpha release.
AB  - The cells and proteases that mediate cigarette smoke-induced emphysema are
      controversial, with evidence favoring either neutrophils and neutrophil-derived
      serine proteases or macrophages and macrophage-derived metalloproteases as the
      important effectors. We recently reported that both macrophage metalloelastase
      (MMP-12) and neutrophils are required for acute cigarette smoke-induced
      connective tissue breakdown, the precursor of emphysema. Here we show how these
      disparate observations can be linked. Both wild-type (MMP-12 +/+) mice and mice
      lacking MMP-12 (MMP-12 -/-) demonstrated rapid increases in whole-lung nuclear
      factor-kappaB activation and gene expression of proinflammatory cytokines after
      cigarette smoke exposure, indicating that a lack of MMP-12 does not produce a
      global failure to upregulate inflammatory mediators. However, only MMP-12 +/+
      mice demonstrated increased whole-lung tumor necrosis factor-alpha (TNF-alpha)
      protein or release of TNF-alpha from cultured alveolar macrophages exposed to
      smoke in vitro. Levels of whole-lung E-selectin, an endothelial activation
      marker, were increased in only MMP-12 +/+ mice. These findings suggest that,
      acutely, MMP-12 mediates smoke-induced inflammation by releasing TNF-alpha from
      macrophages, with subsequent endothelial activation, neutrophil influx, and
      proteolytic matrix breakdown caused by neutrophil-derived proteases. TNF-alpha
      release may be a general mechanism whereby metalloproteases drive cigarette smoke
      induced inflammation.

PMID- 12522031
TI  - Herpesvirus infections in organ transplant recipients.

PMID- 12522032
TI  - Measurement of Chlamydia pneumoniae-specific immunoglobulin A (IgA) antibodies by
      the microimmunofluorescence (MIF) method: comparison of seven fluorescein-labeled
      anti-human IgA conjugates in an in-house MIF test using one commercial MIF and
      one enzyme immunoassay kit.
AB  - For the serological diagnosis of acute Chlamydia pneumoniae infection, the
      microimmunofluorescence (MIF) test is the most commonly used method and also the
      "gold standard" for the measurement of immunoglobulin G (IgG) and IgM antibodies.
      The role of IgA antibodies in diagnosis has not been established. Commercially
      available fluorescein-labeled anti-human IgA conjugates have not been
      systematically compared to each other, and this situation may cause considerable
      variations in IgA results. Therefore, we tested 261 serum samples from 122
      patients with pneumonia for IgA antibodies by using six alpha-chain-specific anti
      IgA conjugates in our in-house MIF test, one commercial MIF test, and one enzyme
      immunoassay (EIA). Interfering IgG antibodies were removed with Gullsorb reagent
      before the measurement of IgA antibodies. Altogether, 14 significant IgA antibody
      increases in serum samples between the acute phase and the convalescent phase
      were detected by at least one of the conjugates in the MIF test, while no
      increases were found in the IgA EIA. Only one patient showed a significant IgA
      antibody increase with all of the fluorescein-labeled conjugates. Five
      significant titer changes were detected by at least two conjugates, and in nine
      instances, the titer increase was detected by one conjugate only. The titer
      agreement indicated by kappa coefficients was very good or good for all of the
      fluorescein-labeled conjugates and the EIA with low antibody titers but decreased
      with increasing titers.

PMID- 12522033
TI  - Neurobehavioral changes resulting from recombinase activation gene 1 deletion.
AB  - Recombinase activation gene 1 (RAG-1) function is essential for V(D)J
      recombination in T-cell-receptor and immunoglobulin rearrangements whereby the
      immune system may encode memories of a vast array of antigens. The RAG-1 gene is
      also localized to neurons in the hippocampal formation and related limbic regions
      that are involved in spatial learning and memory as well as other parameters of
      neurobehavioral performance. Since the unique ability to encode memory is shared
      by the immune system and the brain, we tested the hypothesis that loss of the RAG
      1 gene in the brain would influence learning and memory performance and examined
      several different domains of behavior in RAG-1-knockout and control mice.
      Compared to control mice, RAG-1-knockout mice exhibited increased locomotor
      activity in an open field under both dim and bright lighting conditions and
      decreased habituation (reduction in the expected decline in locomotor activity
      with increasing familiarity with the novel environment in a 1-h test session) in
      bright lighting. RAG-1-knockout mice also showed reduced levels of fearfulness
      for some measures of fear-motivated behavior in both the open-field behavior test
      and elevated-plus maze test. Contrary to our hypothesis, no differences in
      spatial learning and memory were found between the groups, although modest
      differences were observed visible-platform testing in the Morris water maze.
      Neither prepulse inhibition, a measure of sensorimotor gating, nor reflexive
      acoustic startle responses differed between the RAG-1-knockout and control mice.
      It remains to be determined if these changes are due to the loss of RAG-1 gene
      expression in the brain, are due to the absence of the gene in the immune system
      (e.g., the loss of cytokines with neuromodulatory activities), or are due to some
      combination of both effects. Study of the neurobiological actions of RAG-1 in the
      brain may provide new insights into important processes involved in normal brain
      function and disease.

PMID- 12522034
TI  - Effect of multiple freeze-thaw cycles on detection of measles, mumps, and rubella
      virus antibodies.
AB  - We investigated the effect of multiple freeze-thaw cycles on mumps, measles, and
      rubella virus serum antibody levels with whole-virus immunoglobulin G enzyme
      linked immunoassays. Fresh serum samples from nine healthy adult volunteers were
      divided into six sets of five aliquots each. Samples were taken through a total
      of 10 freeze-thaw cycles and stored at 4 degrees C until assayed. Each assay
      measurement was done in replicates of five, and the mean value was reported.
      After completing 10 freeze-thaw cycles, we found no clinically or statistically
      significant effect on measured antibody levels and found no discernible
      detrimental effect on the ability to measure these antibodies by enzyme-linked
      immunoassays.

PMID- 12522035
TI  - Chemokine receptor 5 expression in gastric mucosa of Helicobacter pylori-infected
      and noninfected children.
AB  - Experimental data from human adults or animal models indicate that the
      Helicobacter pylori-specific immune response is dominated by inflammatory T cells
      of the Th1 type. To investigate whether a Th1 immune response is established in
      early H. pylori infection, gastric biopsy samples from 70 children were subjected
      to immunohistochemical analysis. To this end, T cells, B cells, monocytes,
      neutrophils, and chemokine receptor 5 (CCR5)-expressing (CCR5(+)) cells, which
      are associated with Th1 immune responses, were quantified. Children were
      classified according to H. pylori status and clinical, laboratory, and
      macroscopic (during endoscopy) findings, without knowledge of histological
      findings. Group 1 included 31 H. pylori-infected children, group 2 contained 24
      children with other conditions possibly affecting the stomach, and group 3
      contained 15 children without verifiable pathological findings in the stomach.
      Lymphoid follicles were present in 90% of biopsy samples from group 1 and 48% of
      those from group 2 but absent in group 3 biopsy samples. Intraepithelial T cells
      and CCR5(+) cells were regularly detected in all groups without significant
      differences. B cells, monocytes, and neutrophils were not found. In contrast, the
      numbers of lamina propria T cells (P < 0.003) and CCR5(+) cells (P < 0.001) were
      increased significantly in H. pylori-infected children. B cells (in 13 of 66
      children) were detected in children with active (n = 11) or previously cleared (n
      = 2) H. pylori infections but were absent in healthy children. The numbers of
      monocytes (in 10 of 67 children) did not differ among the groups. Calculations
      indicated that the majority of gastric T cells express CCR5; this finding is in
      contrast to the low percentage of CCR5(+) T cells in the peripheral circulation.
      Thus, an increase in the numbers of CCR5(+) cells in H. pylori-infected stomach
      mucosa suggests that this molecule may play an important role in gastric immune
      responses.

PMID- 12522036
TI  - Systemic immunoresponses in mice after repeated exposure of lungs to spores of
      Streptomyces californicus.
AB  - Microbial growth in moisture-damaged buildings is associated with respiratory and
      other symptoms in the occupants. Streptomyces spp. are frequently isolated from
      such buildings. In the present study, we evaluated the responses of mice after
      repeated exposure to spores of Streptomyces californicus. Mice were exposed via
      intratracheal instillation to six doses (at 7-day intervals) of the spores of S.
      californicus, originally isolated from the indoor air of a moisture-damaged
      building, at three dose levels (2 x 10(3), 2 x 10(5), and 2 x 10(7) spores).
      Inflammation and toxicity, including changes in cell populations in the lungs,
      lymph nodes, and spleen, were evaluated 24 h after the last dosage. The exposure
      provoked a dose-dependent inflammatory cell response, as detected by the intense
      recruitment of neutrophils, but the numbers of macrophages and lymphocytes in the
      airways also increased. The cellular responses corresponded to the dose-dependent
      increases in inflammation- and cytotoxicity-associated biochemical markers (i.e.,
      levels of albumin, total protein, and lactate dehydrogenase) in bronchoalveolar
      lavage fluid. The spore exposure increased the number of both activated and
      nonactivated T lymphocytes. Also, the amounts of CD3(-) CD4(-) and unconventional
      CD3(-) CD4(+) lymphocytes in the lung tissue were augmented. Interestingly, the
      spore exposure decreased cells in the spleen. This effect was strongest at the
      dose of 2 x 10(5) spores. These results indicate that the spores of S.
      californicus are capable of provoking both immunostimulation in lungs
      (inflammation) and systemic immunotoxicity, especially in the spleen. The
      immunotoxic effect resembled that caused by chemotherapeutic agents, originally
      isolated from Streptomyces spp. Thus, S. californicus must be considered a
      microbial species with potential to cause systemic adverse health effects in
      occupants of moisture-damaged buildings.

PMID- 12522037
TI  - Competitive enzyme-linked immunosorbent assay based on a rhoptry-associated
      protein 1 epitope specifically identifies Babesia bovis-infected cattle.
AB  - The competitive enzyme-linked immunosorbent assay (cELISA) format has proven to
      be an accurate, reliable, easily standardized, and high-throughput method for
      detecting hemoparasite infections. In the present study, a species-specific,
      broadly conserved, and tandemly repeated B-cell epitope within the C terminus of
      the rhoptry-associated protein 1 of the hemoparasite Babesia bovis was cloned and
      expressed as a histidine-tagged thioredoxin fusion peptide and used as antigen in
      a cELISA. The assay was optimized with defined negative and positive bovine sera,
      where positive sera inhibited the binding of the epitope-specific monoclonal
      antibody BABB75A4. The cELISA accurately differentiated animals with B. bovis
      specific antibodies from uninfected animals and from animals with antibodies
      against other tick-borne hemoparasites (98.7% specificity). In addition, B. bovis
      specific sera from Australia, Argentina, Bolivia, Puerto Rico, and Morocco
      inhibited the binding of BABB75A4, confirming conservation of the epitope. The
      assay first detected experimentally infected animals between 13 and 17 days
      postinfection, and with sera from naturally infected carrier cattle, was
      comparable to indirect immunofluorescence (98.3% concordance). The assay appears
      to have the characteristics necessary for an epidemiologic and disease
      surveillance tool.

PMID- 12522038
TI  - Destructive arthritis in vaccinated interferon gamma-deficient mice challenged
      with Borrelia burgdorferi: modulation by tumor necrosis factor alpha.
AB  - We found that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN
      gamma(0)) mice challenged with B. burgdorferi developed prominent chronic
      destructive osteoarthropathy. When these mice were treated with anti-tumor
      necrosis factor alpha (TNF-alpha) antibody, the severity of the destructive
      osteoarthritis was enhanced and affected the mobility of the animals. In
      addition, extensive swelling of the hind paws occurred. In contrast, treatment of
      B. burgdorferi-vaccinated, challenged IFN-gamma(0) mice with recombinant TNF
      alpha (rTNF-alpha) inhibited the development of arthritis, including swelling of
      the hind paws. Moreover, treatment of vaccinated, challenged IFN-gamma(0) mice
      with anti-TNF-alpha inhibited fourfold the production of an antibody that kills
      B. burgdorferi, while treatment of vaccinated, challenged IFN-gamma(0) mice with
      rTNF-alpha slightly elevated the level of the borreliacidal antibody. These
      results suggest that the level of TNF-alpha directly or indirectly regulates the
      production of borreliacidal antibody and the development of vaccine-induced
      destructive Lyme osteoarthritis. Studies are in progress to determine the
      mechanism by which TNF-alpha-dependent cytokines generate the destructive
      arthritis.

PMID- 12522039
TI  - Alterations in T-cell receptor Vbeta repertoire of CD4 and CD8 T lymphocytes in
      human immunodeficiency virus-infected children.
AB  - Perturbations in the T-cell receptor (TCR) Vbeta repertoire were assessed in the
      CD4 and CD8 T lymphocytes of human immunodeficiency virus (HIV)-infected children
      who were receiving therapy during the chronic phase of infection by flow
      cytometry (FC) and PCR analysis. By FC, representation of 21 TCR Vbeta
      subfamilies was assessed for an increased or decreased percentage in CD4 and CD8
      T cells, and by PCR, 22 TCR Vbeta subfamilies of CD4 and CD8 T cells were
      analyzed by CDR3 spectratyping for perturbations and reduction in the number of
      peaks, loss of Gaussian distribution, or clonal dominance. The majority of the
      TCR Vbeta subfamilies were examined by both methods and assessed for deviation
      from the norm by comparison with cord blood samples. The CD8-T-lymphocyte
      population exhibited more perturbations than the CD4 subset, and clonal dominance
      was present exclusively in CD8 T cells. Of the 55 total CD8-TCR Vbeta families
      classified with clonal dominance by CDR3 spectratyping, only 18 of these
      exhibited increased expression by FC. Patients with high numbers of CD8-TCR Vbeta
      families with decreased percentages had reduced percentages of total CD4 T cells.
      Increases in the number of CD4-TCR Vbeta families with increased percentages
      showed a positive correlation with skewing. Overall, changes from normal were
      often discordant between the two methods. This study suggests that the assessment
      of HIV-induced alterations in TCR Vbeta families at cellular and molecular levels
      yields different information and that our understanding of the immune response to
      HIV is still evolving.

PMID- 12522040
TI  - Enhanced immunological memory responses to Listeria monocytogenes in rodents, as
      measured by delayed-type hypersensitivity (DTH), adoptive transfer of DTH, and
      protective immunity, following Lactobacillus casei Shirota ingestion.
AB  - We have investigated the effect of orally administered Lactobacillus casei
      Shirota (L. casei) on immunological memory, as measured by delayed-type
      hypersensitivity (DTH) and acquired cellular resistance (ACR). The studies were
      performed in animal models in which the animals were rendered immune by a primary
      Listeria monocytogenes infection. It was shown that orally administered viable L.
      casei, and not heat-killed L. casei, enhanced significantly the antigen-specific
      DTH at 24 and 48 h in Wistar rats, Brown Norway rats, and BALB/c mice in a time-
      and dose-dependent fashion. L. casei had to be administered at least 3 days prior
      to the DTH assay at a daily dose of 10(9) CFU in order to induce significant
      effects. Long-term administration of 10(9) CFU of viable L. casei resulted in
      enhanced ACR, as demonstrated by reduced L. monocytogenes counts in the spleen
      and liver and diminished serum alanine aminotransferase activity after
      reinfection. Enhancement of cell-mediated immunological immune responses by L.
      casei was further established in an adoptive transfer study. Naive recipient
      BALB/c mice, which were infused with nonadherent, immunized spleen cells from L.
      casei-fed donor BALB/c mice, showed significantly enhanced DTH responses at 24
      and 48 h compared to recipient mice which received spleen cells from control
      donor mice. In conclusion, orally administered L. casei enhanced cell-mediated
      immunological memory responses. The effects relied on lactobacillus dose and
      viability as well as timing of supplementation and, further, appeared to be
      independent of host species or genetic background.

PMID- 12522041
TI  - Specific detection of human BK polyomavirus in urine samples of immunocompromised
      patients.
AB  - A semiquantitative PCR assay for the detection of BK virus in urine was developed
      using primers for BK virus that specifically amplified BK but not JC virus. DNA
      was extracted from urine through treatment with proteinase K followed by DNA
      precipitation with sodium acetate. Semiquantitation was achieved by amplifying
      serial dilutions (1:1, 1:10, 1:100, and 1:1,000) of the urine specimens. Each
      assay included both positive (stock BK virus and previously positive patient
      urine) and negative (no template) controls. A urine sample was interpreted as
      positive if any of the serial dilutions showed amplification of the DNA fragment
      of the expected size. For some patient-derived samples, amplification of the
      expected-size fragment was achieved with a dilute template whereas no
      amplification was achieved with a concentrated template. This was attributed to
      interfering substances in the urine. PCR results were compared with urine
      cytology and shown to be more sensitive. Validation studies were performed at the
      University of Nebraska Medical Center, utilizing a separate qualitative PCR assay
      that detects both BK and JC virus and distinguishes between them by restriction
      enzyme digestion patterns. Of 46 urine samples analyzed using both methods, 22
      were positive by both assays, 18 were negative by both assays, 5 were positive
      only by the Nebraska method, and 1 was positive only by our method. In comparison
      with the Nebraska PCR, our PCR assay had a sensitivity of 81% and specificity of
      95%. For twenty-one (43%) of 49 immunocompromised patients, tests were positive
      when specimens were submitted because of clinical suspicion of BK virus
      infection.

PMID- 12522042
TI  - Serum interferon (IFN)-neutralizing antibodies and bioactivities of IFNs in
      patients with severe type II essential mixed cryoglobulinemia.
AB  - The efficacy of alpha interferon (IFN-alpha) in the treatment of severe type II
      essential mixed cryoglobulinemia (EMC) has been reported previously. In some
      patients, the development of neutralizing antibodies to recombinant IFN-alpha
      (rIFN-alpha) can affect the clinical response achieved with rIFN-alpha; a second
      treatment with natural IFN-alpha preparations may reinduce the clinical response.
      In the present study the ability of leukocyte IFN (LeIFN) to restore the response
      was investigated from a pharmacodynamic viewpoint. Specifically, the
      pharmacodynamic profiles of different IFN-alpha preparations were studied by
      measuring the serum neopterin levels and the levels of expression of protein MxA
      mRNA in in vivo peripheral blood mononuclear cells in two patients with EMC whose
      resistance to rIFN-alpha2a treatment increased concomitantly with the development
      of neutralizing antibodies. These markers were measured before injection and at
      24 and 48 h after a single injection of rIFN-alpha2a, consensus IFN [(C)IFN], or
      LeIFN. No increase or only a slight increase in MxA mRNA levels was detectable
      after administration of rIFN-alpha2a or (C)IFN, whereas a significant increase
      (>/=10-fold) in MxA mRNA expression was recorded following administration of
      LeIFN. The neutralizing antibodies to rIFN-alpha2a cross-react with (C)IFN. Sera
      from these patients neutralized most but not all of the subtypes present in the
      natural IFN-alpha (LeIFN) mixture, and no significant increase in neopterin
      levels was observed after these patients were switched to LeIFN treatment. In
      summary, the data demonstrate that the problem of neutralizing antibodies still
      exists and that LeIFN may induce an increase in the level of MxA mRNA expression
      but not an increase in neopterin levels in patients who are resistant to
      treatment with rIFN-alpha2a or (C)IFN.

PMID- 12522043
TI  - Evaluation of four commercially available Epstein-Barr virus enzyme immunoassays
      with an immunofluorescence assay as the reference method.
AB  - Four commercially available enzyme immunoassays (EIAs) (Novitec, Biotest,
      Virotech, and DiaSorin) were evaluated, with an indirect immunofluorescence assay
      as the reference method, for Epstein-Barr virus (EBV) VCA (viral capsid antigen)
      immunoglobulin G (IgG), VCA IgM, or EBNA (EBV nuclear antigen) IgG at three
      different locations (Homburg, Stuttgart, and Dresden). Serum samples from 66
      immunocompetent patients with infectious mononucleosis, 73 patients without prior
      EBV infection, and 96 patients with past EBV infections and 29 serum samples with
      possible cross-reactions to other herpesviruses were included. In addition, 25
      samples from an extensively pretested panel that is commercially available
      (Boston Biomedica) were tested. Each sample was tested at only one location. The
      four EIAs varied considerably in performance. When analyzing for EBV diagnosis,
      the Novitec assay performed the best, with 4.9% discrepant diagnoses, followed by
      the Biotest, Virotech, and DiaSorin assays, with 6.8, 11.7, and 14.0% discrepant
      diagnoses, respectively. On the basis of single-parameter analysis, the Novitec
      assay also showed the lowest number of discrepant results, with 3.5%, compared
      with the Virotech, Biotest, and DiaSorin assays, which produced 5.4, 6.4, and
      8.6% discrepant results, respectively. VCA assays using affinity-purified native
      antigens performed better than assays with recombinant or synthetic antigens. The
      synthetic EBNA-1s showed the lowest concordance with the reference compared to
      recombinant p72. Commercially available EBV EIAs differed considerably in
      performance; however, some proved to be reliable and convenient alternatives to
      the indirect immunofluorescence assay for routine diagnostics. Native antigens,
      rather than synthetic peptides, are favored for EBV serology testing.

PMID- 12522044
TI  - Analysis of linear B-cell epitopes of the nucleoprotein of ebola virus that
      distinguish ebola virus subtypes.
AB  - Ebola virus consists of four genetically distinguishable subtypes. We developed
      monoclonal antibodies (MAbs) to the nucleoprotein (NP) of Ebola virus Zaire
      subtype and analyzed their cross-reactivities to the Reston and Sudan subtypes.
      We further determined the epitopes recognized by these MAbs. Three MAbs reacted
      with the three major subtypes and recognized a fragment containing 110 amino
      acids (aa) at the C-terminal extremity. They did not show specific reactivities
      to any 10-aa short peptides in Pepscan analyses, suggesting that these MAbs
      recognize conformational epitope(s) located within this region. Six MAbs
      recognized a fragment corresponding to aa 361 to 461 of the NP. Five of these six
      MAbs showed specific reactivities in Pepscan analyses, and the epitopes were
      identified in two regions, aa 424 to 430 and aa 451 to 455. Three MAbs that
      recognized the former epitope region cross-reacted with all three subtypes, and
      one that recognized the same epitope region was Zaire specific. One MAb, which
      recognized the latter epitope region, was reactive with Zaire and Sudan subtypes
      but not with the Reston subtype. These results suggest that Ebola virus NP has at
      least two linear epitope regions and that the recognition of the epitope by MAbs
      can vary even within the same epitope region. These MAbs showing different
      subtype specificities might be useful reagents for developing an immunological
      system to identify Ebola virus subtypes.

PMID- 12522046
TI  - Western immunoblotting for Bartonella endocarditis.
AB  - To differentiate infectious endocarditis (IE) from other Bartonella infections
      and to identify infecting Bartonella bacteria at the species level on a
      serological basis, we used Western immunoblotting to test sera from 51 patients
      with Bartonella IE (of which 27 had previously benefited from species
      identification by molecular techniques), 11 patients with chronic Bartonella
      quintana bacteremia, and 10 patients with cat scratch disease. Patients with IE
      were Western blot positive in 49 of 51 cases, and significant cross-reactivity
      with three heterologous Bartonella antigens was found in 45 of 49 cases. Sera
      from bacteremic patients did not react with more than one heterologous antigen,
      and sera from patients with cat scratch disease gave negative results. Sera
      reacted only with B. henselae in four cases of IE, including one with a positive
      PCR result for valve tissue. Western blot and cross-adsorption performed on serum
      samples from patients with IE (the identity of the causative species having been
      determined by PCR) were demonstrated to identify efficiently the causative
      species in all cases. When applied to patients diagnosed on the basis of
      serological tests only, this technique allowed identification of the causative
      species in 20 of 22 cases. The results were in accordance with epidemiological
      features. Six reactive bands of B. quintana (of molecular sizes from 10 to 83
      kDa) demonstrated significant association with sera from patients with B.
      quintana endocarditis. Overall, Western blotting and cross-adsorption made it
      possible to identify the causative species in 49 of 51 (96%) IE cases.

PMID- 12522045
TI  - Specificity and diversity of antibodies to Mycobacterium tuberculosis
      arabinomannan.
AB  - Arabinomannan (AM) is a polysaccharide antigen of the mycobacterial capsule.
      However, it is uncertain whether AM constitutes an immunologically distinct
      fraction of Mycobacterium tuberculosis. In this study, we analyzed the repertoire
      and specificity of antibodies to AM by using AM-binding murine monoclonal
      antibodies (MAbs) and human serum samples. Murine MAbs were found to be diverse
      in their specificity to AM and cross-reactivity with other arabinose-containing
      mycobacterial polysaccharides, with MAb 9d8 binding exclusively to AM. Human
      antibodies to AM were detected in serum samples from patients with pulmonary
      tuberculosis (TB), as well as in those from healthy, purified protein derivative
      negative controls, with significantly higher titers among patients. The binding
      of human antibodies to AM was inhibited by MAb 9d8 in three patients with TB but
      not in controls. MAb 5c11, which recognizes other mycobacterial arabinose
      containing carbohydrates in addition to AM, inhibited the binding of serum
      samples from 75% of patients and 76% of controls. Analysis of human antibodies
      with murine MAbs to human V(H) determinants demonstrated diversity among
      antibodies to AM with qualitative and quantitative differences compared with
      antibodies to lipoarabinomannan. In summary, our study suggests that antibodies
      to AM are diverse and heterogeneous with respect to antigen recognition and V(H)
      determinant expression, with human serum samples containing different subsets of
      antibodies to AM with the specificities of AM-binding murine MAbs. One MAb and a
      subset of human antibodies bind AM specifically, suggesting that this
      polysaccharide is antigenically distinct and is expressed in human infection.

PMID- 12522047
TI  - Characterization of the humoral immune response to Chlamydia outer membrane
      protein 2 in chlamydial infection.
AB  - Detection of antibodies to an outer membrane protein 2 (OMP2) by enzyme-linked
      immunosorbent assay (ELISA) by using either the Chlamydia trachomatis- or the
      Chlamydia pneumoniae-specific protein was investigated. OMP2 is an immunodominant
      antigen giving rise to antibody responses in humans infected with different C.
      trachomatis serovars (A to C and D to K) or with C. pneumoniae, which could be
      detected by OMP2 ELISA. OMP2 ELISA is not species specific, but antibody titers
      were usually higher on the homologous protein. The sensitivity of this assay was
      high but varied according to the "gold standard" applied. Levels of antibody to
      C. pneumoniae OMP2 as detected by ELISA seem to return to background or near
      background values within a shorter period of time compared to antibodies to C.
      pneumoniae detected by microimmunofluorescence (MIF), making it more likely that
      positive results in ELISA reflect recent infection. Thus, OMP2 ELISA has distinct
      advantages over MIF and commercially available ELISAs and might be a useful tool
      for the serodiagnosis of chlamydial infection.

PMID- 12522048
TI  - Simultaneous quantitation of antibodies to neutralizing epitopes on virus-like
      particles for human papillomavirus types 6, 11, 16, and 18 by a multiplexed
      luminex assay.
AB  - Several different methods have been developed to quantitate neutralizing antibody
      responses to human papillomaviruses (HPVs), including in vivo neutralization
      assays, in vitro pseudoneutralization assays, competitive radioimmunoassays
      (cRIAs), and enzyme-linked immunosorbent assays. However, each of these
      techniques possesses one or more limitations that preclude testing large numbers
      of patient sera for use in natural history studies and large vaccine clinical
      trials. We describe here a new multiplexed assay, by using the Luminex Laboratory
      MultiAnalyte Profiling (LabMAP3) assay system, that can simultaneously quantitate
      neutralizing antibodies to human papillomavirus types 6, 11, 16, and 18 in 50
      micro l of serum. The HPV-Luminex competitive immunoassay measures titers of
      polyclonal antibodies in serum capable of displacing phycoerythrin-labeled
      detection monoclonal antibodies binding to conformationally sensitive,
      neutralizing epitopes on the respective virus-like particles. This competitive
      Luminex immunoassay was found to be as sensitive, accurate, and precise as the
      currently used cRIAs. An effective HPV vaccine will most likely require several
      distinct genotypes to protect against multiple cancer causing papillomaviruses.
      The HPV-Luminex immunoassay should prove to be a useful tool in simultaneously
      quantitating antibody immune responses to multiple HPV genotypes for natural
      history infection studies and for monitoring the efficacy of prospective
      vaccines.

PMID- 12522049
TI  - Decreased epithelial cytokine responses in the duodenal mucosa of Helicobacter
      pylori-infected duodenal ulcer patients.
AB  - Helicobacter pylori colonizes the human stomach and areas of gastric metaplasia
      in the duodenum, but only a minority of those that are infected develop symptoms,
      e.g., peptic ulcers. Although most ulcers occur in the duodenum, almost all
      studies of mucosal immune responses against the infection have been limited to
      responses in the stomach. In the present study we evaluated whether there are
      differences in the levels of proinflammatory cytokines as well as
      immunoregulatory cytokines in the duodenal mucosa of duodenal ulcer (DU) patients
      and asymptomatic (AS) carriers which may be related to the development of
      duodenal ulcers. Duodenal biopsy specimens collected from normal mucosa as well
      as metaplastic mucosa of DU patients, AS carriers, and uninfected controls were
      analyzed for a number of cytokines by immunohistochemistry. Interestingly, the
      level of epithelial staining for several cytokines, e.g., interleukin-8 (IL-8),
      transforming growth factor beta (TGF-beta), and gamma interferon (IFN-gamma), was
      found to be significantly lower in DU patients than in AS carriers and uninfected
      individuals. No differences were observed when cytokine staining in normal and
      metaplastic biopsy specimens was compared. However, larger numbers of IL-8-, IL-6
      , TGF-beta-, and IFN-gamma-positive mononuclear cells were observed in the
      duodenal lamina propria of both DU patients and AS carriers than in that of the
      uninfected controls. Our finding that a number of cytokines that may be important
      for the mucosal host defense against H. pylori are strongly decreased in the
      duodenal epithelium of ulcer patients suggests that a down-regulated immune
      response plays a role in the development of duodenal ulcers.

PMID- 12522050
TI  - Identification of B- and T-cell epitopes of BB, a carrier protein derived from
      the G protein of Streptococcus strain G148.
AB  - Most conventional vaccines consist of killed organisms or purified antigenic
      proteins. Such molecules are generally poorly immunogenic and need to be coupled
      to carrier proteins. We have identified a new carrier molecule, BB, derived from
      the G protein of Streptococcus strain G148. We show that BB is able to induce
      strong antibody responses when conjugated to peptides or polysaccharides. In
      order to localize T and B cell epitopes in BB and match them with the albumin
      binding region of the molecule, we immunized mice with BB, performed B and T
      pepscan analyses, and compared the results with pepscan done with sera and cells
      from humans. Our results indicate that BB has two distinct T helper epitopes,
      seven linear B-cell epitopes, and one conformational B-cell epitope in BALB/c
      mice. Four linear B-cell epitopes were identified from human sera, three of which
      overlapped mouse B-cell epitopes. Finally, three human T-cell epitopes were
      detected on the BB protein. One of these T-cell epitopes is common to BALB/c mice
      and humans and was localized in the region that contains the albumin-binding
      site. These data are of interest for the optimization of new carrier molecules
      derived from BB.

PMID- 12522051
TI  - Simultaneous detection of 15 human cytokines in a single sample of stimulated
      peripheral blood mononuclear cells.
AB  - Cytokines secreted by cells of the immune system can alter the behavior and
      properties of immune or other cells. At a site of inflammation, sets of cytokines
      interact with immune cells, and their combined effect is often more important
      than the function of one isolated component. Conventional techniques, such as
      enzyme-linked immunosorbent assays, generally require large quantities of cells
      to characterize a complete cytokine profile of activated lymphocytes. The Bio
      Plex system from Bio-Rad Laboratories combines the principle of a sandwich
      immunoassay with the Luminex fluorescent-bead-based technology. We developed a
      multiplex cytokine assay to detect different cytokines simultaneously in culture
      supernatant of human peripheral blood mononuclear cells stimulated with antigen
      and with mitogen. Fifteen human cytokines (interleukin 1alpha [IL-1alpha], IL
      1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-18,
      gamma interferon, and tumor necrosis factor alpha) were validated with a panel of
      healthy individuals, rheumatoid arthritis patients, and juvenile idiopathic
      arthritis patients. Comparing the multiplex assay with a regular enzyme-linked
      immunosorbent assay technique with this donor panel resulted in correlation
      coefficients for all cytokines ranging from 0.75 to 0.99. Intra-assay variance
      proved to be less then 10%, whereas interassay variability ranged between 10 and
      22%. This multiplex system proved to be a powerful tool in the quantitation of
      cytokines. It will provide a more complete picture in differences between
      activated lymphocyte cytokine profiles from healthy individuals and those from
      patients with chronic inflammatory diseases.

PMID- 12522053
TI  - Use of vesicular stomatitis virus pseudotypes bearing hantaan or seoul virus
      envelope proteins in a rapid and safe neutralization test.
AB  - A vesicular stomatitis virus (VSV) pseudotype bearing hantavirus envelope
      glycoproteins was produced and used in a neutralization test as a substitute for
      native hantavirus. The recombinant VSV, in which the enveloped protein gene (G)
      was replaced by the green fluorescent protein gene and complemented with G
      protein expressed in trans (VSVDeltaG*G), was kindly provided by M. A. Whitt.
      293T cells were transfected with plasmids for the expression of envelope
      glycoproteins (G1 and G2) of HTNV or SEOV and were then infected with
      VSVDeltaG*G. Pseudotype VSV with the Hantaan (VSVDeltaG*-HTN) or Seoul
      (VSVDeltaG*-SEO) envelope glycoproteins were harvested from the culture
      supernatant. The number of infectious units (IU) of the pseudotype VSVs ranged
      from 10(5) to 10(6)/ml. The infectivity of VSVDeltaG*-HTN and VSVDeltaG*-SEO was
      neutralized with monoclonal antibodies, immune rabbit sera, and sera from
      patients with hemorrhagic fever with renal syndrome, and the neutralizing titers
      were similar to those obtained with native hantaviruses. These results show that
      VSVDeltaG*-HTN and -SEO can be used as a rapid, specific, and safe neutralization
      test for detecting hantavirus-neutralizing antibodies as an effective substitute
      for the use of native hantaviruses. Furthermore, the IU of VSVDeltaG*-HTN and 
      SEO did not decrease by more than 10-fold when stored at 4 degrees C for up to 30
      days. The stability of the pseudotype viruses allows distribution of the material
      to remote areas by using conventional cooling boxes for use as a diagnostic
      reagent.

PMID- 12522054
TI  - Keratinocyte expression of human beta defensin 2 following bacterial infection:
      role in cutaneous host defense.
AB  - Human beta defensin 2 (hbetaD-2) is thought to play an important role in
      cutaneous immune defense. We hypothesized that (i) keratinocyte expression of
      hbetaD-2, measured by reverse transcription-PCR, would be upregulated in response
      to challenge with pathogenic bacteria, particularly highly adherent strains of
      Streptococcus pyogenes and Staphylococcus aureus, and (ii) hbetaD-2 would have
      potent antimicrobial activity against pathogenic but not commensal organisms.
      Expression of hbetaD-2 was induced consistently by S. aureus, Staphylococcus
      epidermidis, Escherichia coli, and Pseudomonas aeruginosa, whereas strains of S.
      pyogenes were poor and variable inducers of hbetaD-2. No correlation was found
      between levels of bacterial adherence and keratinocyte expression of hbetaD-2. S.
      pyogenes was significantly more sensitive to killing by hbetaD-2 than S.
      epidermidis. We conclude that the ability to induce hbetaD-2 expression in
      combination with sensitivity to its antimicrobial effects may contribute to the
      rarity of skin infections with the gram-negative bacterial organisms, whereas
      lack of stimulation of hbetaD-2 expression by S. pyogenes may be important in its
      ability to evade innate defenses and cause skin disease. Induction of expression
      of hbetaD-2 but relative tolerance to it may enable S. epidermidis to survive on
      the skin surface and modulate hbetaD-2 expression when the stratum corneum
      barrier is disrupted.

PMID- 12522052
TI  - Functional and morphological development of lymphoid tissues and immune
      regulatory and effector function in rhesus monkeys: cytokine-secreting cells,
      immunoglobulin-secreting cells, and CD5(+) B-1 cells appear early in fetal
      development.
AB  - Little is known regarding the timing of immune ontogeny and effector function in
      fetal humans and nonhuman primates. We studied the organization of lymphocyte and
      antigen-presenting cell populations in developing lymphoid tissues of rhesus
      monkey fetuses during the second and third trimesters (65 to 145 days of
      gestation; term = 165 days). Immunoglobulin-secreting and cytokine-secreting
      cells were detected at day 80. The thymus, spleen, lymph nodes, and intestinal
      mucosa were examined for cells expressing CD3, CD5, CD20, CD68, p55, and HLA-DR.
      In the spleens of 65-day-old fetuses (early second trimester), the overwhelming
      majority of total lymphocytes were CD5(+) CD20(+) B-1 cells. The remaining
      lymphocytes were CD3(+) T cells. By day 80, splenic B and T cells were equal in
      number. Intraepithelial CD3(+) CD5(-) T cells and lamina propria CD20(+) CD5(+) B
      cells were present in the intestines of 65-day-old fetuses. By day 80, numerous
      CD20(+) CD5(+) B cells were present in the jejunums and colons and early
      lymphocyte aggregate formation was evident. The spleens of 80- to 145-day-old
      fetuses contained immunoglobulin M (IgM)-secreting cells, while IgA-, IgG-,
      interleukin-6-, and gamma interferon-secreting cells were numerous in the spleens
      and colons. Thus, by the second trimester, the lymphoid tissues of the rhesus
      monkey fetus have a complete repertoire of properly organized antigen-presenting
      cells, T cells, and B cells.

PMID- 12522055
TI  - Elevated fecal Candida counts in patients with antibiotic-associated diarrhea:
      role of soluble fecal substances.
AB  - To assess the role of soluble fecal substances in the elevation of fecal Candida
      counts in patients with antibiotic-associated diarrhea (AAD), we investigated the
      growth of Candida albicans in vitro in serially diluted stool fluids from
      patients with AAD and healthy subjects. There were significantly higher Candida
      albicans counts in stool fluids diluted 1:10 from AAD patients than in healthy
      subjects and the phosphate-buffered saline growth control, which may be due to
      reduced soluble Candida inhibitors and increased availability of growth factors
      and nutrients.

PMID- 12522056
TI  - Assessment of safety of lactobacillus strains based on resistance to host innate
      defense mechanisms.
AB  - Seven Lactobacillus strains belonging to four species were evaluated for
      pathogenicity as well as for in vitro sensitivity to the bactericidal mechanisms
      of macrophages in a rabbit infective endocarditis (IE) model. Two bacteremia
      associated strains, L. rhamnosus PHLS A103/70 and L. casei PHLS A357/84, as well
      as the L. rhamnosus type strain and the probiotic L. rhamnosus strain ATCC 53103,
      showed moderate infectivity, and the virulence of the probiotic L. casei strain
      Shirota and type strains such as L. acidophilus ATCC 4356(T) and L. gasseri DSM
      20243(T) in the model was negligible. The strains that showed pathogenic
      potential in the rabbit IE model (PHLS A357/84, PHLS A103/70, and ATCC 53103)
      were more resistant than strain Shirota to intracellular killing activity by
      mouse macrophages in vitro and also to bactericidal nitrogen intermediates, such
      as nitric oxide and NO(2)(-) ions. These results suggest that resistance to host
      innate defense systems, which would function at inflammatory lesions, should be
      considered in the safety assessment of Lactobacillus strains.

PMID- 12522057
TI  - Comparison of serological assays for detection of Chlamydia trachomatis
      antibodies in different groups of obstetrical and gynecological patients.
AB  - New serological enzyme immunoassays (EIAs) were compared with
      microimmunofluorescence (MIF) as a "gold standard" to detect Chlamydia
      trachomatis antibodies in different groups of obstetrical, gynecological, and
      subfertile patients. There were no significant differences in seroprevalence
      rates, except for the group of C. trachomatis-positive patients (P < 0.01). Test
      characteristics were calculated for Chlamydia-EIA (Biologische Analysensystem
      GmbH, Lich, Germany) and pELISA (Medac, Wedel, Germany). pELISA seems to be a
      good alternative to MIF. It has high specificity and is easier to perform.

PMID- 12522058
TI  - Performance characteristics of an in-house assay system used to detect West Nile
      Virus (WNV)-specific immunoglobulin M during the 2001 WNV season in the United
      States.
AB  - During the 2001 U. S. West Nile virus (WNV) season, 163 specimens were reactive
      in an in-house WNV-specific immunoglobulin M (IgM) screening enzyme-linked
      immunosorbent assay (ELISA) and were referred to either the Centers for Disease
      Control and Prevention or the appropriate state public health laboratory
      (CDC/SPHL) for additional testing. CDC/SPHL supplied results for 124 specimens
      that could be further evaluated in-house: 70 specimens were nonreactive in the
      CDC/SPHL WNV-specific IgM screening assay, and 54 specimens were reactive. These
      specimens were used to evaluate a modified in-house WNV-specific IgM ELISA that
      incorporated background subtraction to identify nonspecific reactivity and thus
      improve assay specificity. Of the 70 CDC/SPHL nonreactive samples, 49 (70%) were
      nonreactive in the modified ELISA; of the 54 CDC/SPHL reactive samples, 51 (94%)
      were reactive in the modified ELISA. Confirmatory studies performed by CDC/SPHL
      indicated that 38 CDC/SPHL screen-reactive specimens represented true WNV
      infection; all 38 specimens were reactive in the modified in-house WNV-specific
      IgM ELISA. These findings demonstrate that an in-house ELISA system for WNV
      specific IgM effectively identifies patients with WNV infection.

PMID- 12522059
TI  - Immunoglobulin G antibodies against the endosymbionts of filarial nematodes
      (Wolbachia) in patients with pulmonary dirofilariasis.
AB  - The dog parasite Dirofilaria immitis can infect humans. Patients with pulmonary
      dirofilariasis were tested for immunoglobulin G (IgG) antibodies against the
      surface protein of Wolbachia, the bacterial endosymbiont of D. immitis. These
      patients showed significantly higher IgG titers than healthy individuals from
      areas in which D. immitis was endemic as well as areas in which it was not
      endemic. Titration of anti-Wolbachia surface protein IgG could become useful for
      diagnostic applications.

PMID- 12522060
TI  - Infection exclusion of the rickettsial pathogen anaplasma marginale in the tick
      vector Dermacentor variabilis.
AB  - Anaplasma marginale is a tick-borne, rickettsial cattle pathogen that is endemic
      in several areas of the United States. Recent studies (J. de la Fuente, J. C.
      Garcia-Garcia, E. F. Blouin, J. T. Saliki, and K. M. Kocan, Clin. Diagn. Lab.
      Immunol. 9:658-668, 2002) demonstrated that infection of cultured tick cells and
      bovine erythrocytes with one genotype of A. marginale excluded infection with
      other genotypes, a phenomenon referred to as infection exclusion. The present
      study was undertaken to confirm the phenomenon of infection exclusion of A.
      marginale genotypes in a tick vector, Dermacentor variabilis. Only one genotype
      of A. marginale (Virginia isolate) was detected by PCR in ticks that fed first on
      a calf infected with a Virginia isolate and second on a calf infected with an
      Oklahoma isolate. These studies demonstrate that infection exclusion of A.
      marginale genotypes also occurs in naturally infected ticks, as well as in cattle
      and cultured tick cells, and results in establishment of only one genotype per
      tick.

PMID- 12522061
TI  - Experimental mucosal infection with molecularly cloned feline immunodeficiency
      viruses.
AB  - Four of six specific pathogen-free cats were infected after intravaginal exposure
      to molecularly cloned lymphotropic but non-Crandell feline kidney (CRFK)-tropic
      feline immunodeficiency virus strain TM2 and its AP-1 deletion mutant. The
      sequences of the env V3-to-V5 region which defines the CRFK tropism were
      unchanged in the infected cats through the infection. These data suggest that the
      strain was transmitted across the mucosal epithelium without a broadening of cell
      tropism.

PMID- 12522062
TI  - Detection of low-avidity immunoglobulin G in oral fluid samples: new approach for
      rubella diagnosis and surveillance.
AB  - Low-avidity rubella immunoglobulin G (IgG) was detected in oral fluid samples
      from 30 of 32 rubella IgM-positive patients (sensitivity, 94%) and from 4 of 34
      IgM-negative patients (specificity, 88%). Measuring IgG avidity in oral fluid
      samples could improve the reliability of rubella surveillance when the incidence
      of the disease and the positive predictive value of IgM tests are low.

PMID- 12522063
TI  - P-glycoprotein expression by peripheral blood mononuclear cells from human
      immunodeficiency virus-infected patients is independent from response to highly
      active antiretroviral therapy.

PMID- 12522064
TI  - Quality assurance considerations in cryptosporidium antibody tests.

PMID- 12522065
TI  - P2Ys go neuronal: modulation of Ca2+ and K+ channels by recombinant receptors.

PMID- 12522066
TI  - Calcium-impermeable monovalent cation channels: a TRP connection?

PMID- 12522067
TI  - The anti-relapse compound acamprosate inhibits the development of a conditioned
      place preference to ethanol and cocaine but not morphine.
AB  - The effects of the anti-relapse compound acamprosate (calcium
      acetylhomotaurinate) on the conditioned rewarding effects of ethanol, cocaine and
      morphine were studied using the conditioned place preference (CPP) paradigm.
      During 3 days of drug conditioning, mice were pretreated with saline or
      acamprosate (30, 100 or 300 mg kg(-1) i.p.) 10 min prior to the administration of
      ethanol (2 g kg(-1) i.p.), cocaine (15 mg kg(-1) i.p.) or morphine (10 mg kg(-1)
      i.p.), and subsequently confined to one of two distinct conditioning chambers. On
      the following day, mice were tested for the expression of CPP. Acamprosate dose
      dependently reduced the development of CPP to ethanol and cocaine but not
      morphine. When tested as the conditioning drug, acamprosate alone produced
      neither a conditioned place preference nor aversion. These data suggest that
      acamprosate can suppress the conditioned rewarding effects of ethanol and certain
      classes of abused substances.

PMID- 12522068
TI  - Up-regulation of kinin B1 receptor in the lung of streptozotocin-diabetic rat:
      autoradiographic and functional evidence.
AB  - 1 The function and autoradiographic binding expression of kinin B(1) receptors
      were evaluated in the lungs of Streptozotocin (STZ)-diabetic rats. 2 The
      intrapleural injection (i.pl.) of des-Arg(9)-bradykinin (des-Arg(9)-BK) (50 and
      100 nmol per site), a selective B(1) receptor agonist, increased time-dependently
      the mononuclear and neutrophil cells influx in the pleural cavity of rats treated
      with STZ (65 mg kg(-1), i.p., 4 days earlier). This effect was significantly less
      in control rats. 3 The influx of mononuclear and polymorphonuclear neutrophil
      cells induced by des-Arg(9)-BK was significantly inhibited by two B(1) receptor
      antagonists (des-Arg(10)-Hoe140 or R-715, 100 nmol per site, 5 min earlier), but
      not by two B(2) receptor antagonists (Hoe140, 10 nmol or NPC 18884, 100 nmol per
      site, 5 min earlier). However, Hoe140 prevented the higher basal leukocyte influx
      seen in STZ-diabetic rats. 4 Leukocyte infiltration induced by des-Arg(9)-BK in
      STZ-diabetic rats was significantly reduced after treatment with insulin (2 U per
      day, s.c. over 4 days) or with an anti-PMN antibody (0.1 ml of a 1 : 20 dilution,
      i.pl. 5 min earlier). 5 Specific B(1) receptor binding sites were seen in lung
      sections from both control and STZ-diabetic rats, yet the density of labelling
      was much greater in diabetic rats and particularly after intrapleural injection
      of des-Arg(9)-BK. Treatment with insulin or with the anti-PMN antibody markedly
      reduced B(1) receptor binding sites occurring after the injection of des-Arg(9)
      BK in STZ-diabetic rats. 6 Data suggest that the B(1) receptor is up-regulated in
      the lungs of STZ-diabetic rats, and its activation increases leukocyte
      infiltration into the pleural cavity. The overexpression of B(1) receptors seems
      to depend on neutrophils influx and appears to be associated with hyperglycaemia.

PMID- 12522069
TI  - Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced
      plasma extravasation.
AB  - 1 Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the
      dorsal skin of animals. In the present study, we investigated the mechanisms of
      oedema induced by the toxin. 2 The toxin induced plasma extravasation in the
      dorsal skin of Balb/c mice. 3 The extravasation was significantly inhibited by
      diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not
      cause the release of histamine from mouse mastocytoma cells. 4 Tachykinin NK(1)
      receptor antagonists, [D-Pro(2), D-Trp(7,9)]-SP, [D-Pro(4), D-Trp(7,9)]-SP and
      spantide, inhibited the toxin-induced leakage in a dose-dependent manner.
      Furthermore, the non-peptide tachykinin NK(1) receptor antagonist, SR140333,
      markedly inhibited the toxin-induced leakage. 5 The leakage induced by the toxin
      was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not
      affected by systemic pretreatment with a calcitonin gene-related peptide receptor
      antagonist (CGRP(8-37)). 6 The toxin-induced leakage was significantly inhibited
      by the N-type Ca(2+) channel blocker, omega-conotoxin MVIIA, and the bradykinin
      B(2) receptor antagonist, HOE140 (D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]
      bradykinin), but was not affected by the selective L-type Ca(2+) channel blocker,
      verapamil, the P-type Ca(2+) channel blocker, omega-agatoxin IVA, tetrodotoxin
      (TTX), the TTX-resistant Na(+) channel blocker, carbamazepine, or the sensory
      nerve conduction blocker, lignocaine. 7 These results suggest that plasma
      extravasation induced by beta-toxin in mouse skin is mediated via a mechanism
      involving tachykinin NK(1) receptors.

PMID- 12522070
TI  - Anomalous effect of anthracene-9-carboxylic acid on calcium-activated chloride
      currents in rabbit pulmonary artery smooth muscle cells.
AB  - 1 Ca(2+)-activated Cl(-) currents (I(Cl(Ca))) evoked by K(+)-free pipette
      solutions containing 500 nM Ca(2+) were recorded in rabbit pulmonary artery
      smooth muscle cells. A voltage step protocol in which the cells were stepped to
      +70 mV and then to -80 mV produced outward and inward Cl(-) currents respectively
      that exhibited distinctive voltage- and time-dependent kinetics that remained
      consistent for the recording period. 2 Application of the Cl(-) channel inhibitor
      anthracene-9-carboxylic acid (A-9-C, 500 micro M), produced a small inhibition of
      the maximum outward Cl(-) current at +70 mV (21+/-10%) but augmented the
      amplitude of the instantaneous inward relaxation at -80 mV by 321+/-34% (n=12). 3
      The current recorded in the absence and presence of A-9-C reversed at the
      theoretical Cl(-) equilibrium potential and the reversal potential was shifted by
      about -40 mV upon replacement of external chloride ion by the more permeant anion
      thiocyanate. Currents in the absence and presence of A-9-C were similarly
      affected by 100 micro M niflumic acid. 4 Augmentation of the inward current at 
      80 mV by A-9-C required prior depolarization, i.e. A-9-C did not simply activate
      a Cl(-) current at negative membrane potentials. Moreover the degree of
      augmentation was independent of the internal Ca(2+) for concentrations between
      100 nM and 1 micro M Ca(2+). 5 The data from the present study confirm previous
      observations that the inhibitory effect of Cl(-) channel blockers is modified
      when [Ca(2+)](i) is maintained at higher than normal resting concentrations.

PMID- 12522071
TI  - Acetylcholine-induced vasodilation may depend entirely upon NO in the femoral
      artery of young piglets.
AB  - 1 To characterize agonist-induced relaxation in femoral artery rings from young
      piglets, we compared the effect of a NOS-inhibitor N(omega)-nitro-L-arginine (L
      NOARG), an NO-inactivator oxyhaemoglobin (HbO) and a soluble guanyl cyclase(sGC)
      inhibitor 1H-[1,2,4]Oxadiazolo-[4,3,-alpha]quinoxalin-1-one (ODQ) on
      acetylcholine(ACh)-induced relaxation. The involvement of K(+) channel activation
      was studied on relaxations induced by ACh, the two NO donors sodium nitroprusside
      (SNP) and diethylamine (DEA) NONOate, and the cell membrane permeable guanosine
      3'5' cyclic monophosphate (cGMP) analogue 8-Br-cGMP. 2 Full reversal of
      phenylephrine-mediated precontraction was induced by ACh (1 nM-1 microM) (pD(2)
      8.2+/-0.01 and R(max) 98.7+/-0.3%). L-NOARG (100 microM) partly inhibited
      relaxation (pD(2) 7.4+/-0.02 and R(max) 49.6+/-0.8%). The L
      NOARG/indomethacin(IM)-resistant response displayed characteristics typical for
      endothelium-derived hyperpolarizing factor (EDHF), being sensitive to a
      combination of the K(+) channel blockers charybdotoxin (CTX) (0.1 microM) and
      apamin (0.3 microM). 3 ODQ (10 microM) abolished relaxations induced by ACh and
      SNP. L-NOARG/IM-resistant relaxations to ACh were abolished by HbO (20 microM). 4
      Ouabain (1 microM) significantly inhibited ACh-induced L-NOARG/IM-resistant
      relaxations and relaxations induced by SNP (10 microM) and 8-Br-cGMP (0.1 mM). A
      combination of ouabain and Ba(2+) (30 microM) almost abolished L-NOARG/IM
      resistant ACh-induced relaxation (R(max) 7.7+/-2.5% vs 23.4+/-6.4%, with and
      without Ba(2+), respectively, P<0.05). 5 The present study demonstrates that in
      femoral artery rings from young piglets, despite an L-NOARG/IM-resistant
      component sensitive to K(+) channel blockade with CTX and apamin, ACh-induced
      relaxation is abolished by sGC-inhibition or a combination of L-NOARG and HbO.
      These findings suggest that relaxation can be fully explained by the NO/cGMP
      pathway.

PMID- 12522072
TI  - Regulation of muscarinic receptor function in developing oligodendrocytes by
      agonist exposure.
AB  - 1 Oligodendrocytes, the myelin forming cells in the CNS, express muscarinic
      acetylcholine receptors (mAChR), primarily M3, coupled to various signal
      transduction pathways. 2 In the present study we have investigated whether mAChR
      undergo functional agonist-induced regulation in cultured oligodendrocyte
      progenitors and differentiated oligodendrocytes. 3 The muscarinic agonist,
      carbachol (CCh) caused a time-dependent desensitization of phosphoinositide (PI)
      hydrolysis, and the internalization and down-regulation of receptors. Short-time
      desensitization (5 min) of PI hydrolysis occurred without receptor
      internalization and reached 54% by 1 h. The same treatment decreased cell surface
      receptors labelled with the non-permeable ligand [(3)H]-NMS by 47%, while total
      receptor density ([(3)H]-scopolamine binding) decreased by 30%. Longer CCh
      treatment down-regulated receptors by 70% and desensitized the PI response by
      80%. 4 Although protein kinase C (PKC) activation desensitized mAChR, CCh
      mediated desensitization was independent of PKC. 5 Inhibition of receptor
      endocytosis by low temperature during the pre-stimulation period or in the
      presence of hyperosmotic sucrose (0.5 M) blocked desensitization, receptor
      internalization and down-regulation. 6 Recovery of surface mAChR and their
      functional activity following down-regulation was slow, returning to control
      levels by 24 h after agonist removal. In progenitor cells, dose-response curves
      for CCh-mediated PI hydrolysis and c-fos mRNA expression showed that newly
      synthesized mAChR were supersensitive after recovery. 7 Overall, the present
      results provide evidence of functional agonist-mediated mAChR regulation in brain
      oligodendroglial cells.

PMID- 12522073
TI  - Shaker-type Kv1 channel blockers increase the peristaltic activity of guinea-pig
      ileum by stimulating acetylcholine and tachykinins release by the enteric nervous
      system.
AB  - 1 A constant intraluminal pressure system was used to evaluate the effects of Kv1
      channel blockers on the peristaltic activity of guinea-pig ileum. 2 The
      nortriterpene correolide, a non-selective inhibitor of all Kv1 sub-types, causes
      progressive and sustained reduction of the pressure threshold for eliciting
      peristaltic contractions. 3 Margatoxin (MgTX), alpha-dendrotoxin (alpha-DTX) and
      dendrotoxin-K (DTX-K), highly selective peptidyl inhibitors of certain Kv1 sub
      types, cause immediate reduction of the pressure threshold. This effect subsides
      with time, irrespective of the peptides' concentration in the bath. In
      preparations pretreated with saturating concentrations of MgTX, correolide
      further stimulates the peristaltic activity. 4 Iberiotoxin (IbTX), a selective
      inhibitor of the high-conductance Ca(2+)-activated K(+) (BK) channels, and
      charybdotoxin (ChTX), which inhibits Kv1.2 and Kv1.3 as well as BK channels, fail
      to stimulate the peristaltic activity. 5 Blockade of muscarinic receptors by
      atropine reduces, and occasionally suppresses the peristaltic activity of guinea
      pig ileum. In atropine-treated preparations, correolide and MgTX retain their
      abilities to reduce the pressure threshold and are able to restore the
      peristaltic reflex in the preparations where this reflex was suppressed by
      atropine. 6 The stimulatory effect of correolide and MgTX in atropine-treated
      preparations is abolished by subsequent addition of selective antagonists of both
      NK1 and NK2 receptors. 7 In conclusion, blockade of Kv1, particularly Kv1.1
      channels, increases the peristaltic activity of guinea-pig ileum by enhancing the
      release of neurotransmitters at the enteric nervous system. In contrast,
      stimulation of the myogenic motility by blockade of BK channels does not affect
      the threshold for the peristaltic reflex.

PMID- 12522074
TI  - Activation and potentiation of the NO/cGMP pathway by NG-hydroxyl-L-arginine in
      rabbit corpus cavernosum under normoxic and hypoxic conditions and ageing.
AB  - 1 When nitric oxide synthase (NOS) produces NO from N(G)-hydroxy-L-arginine (OH
      arginine) instead of L-arginine, the total requirement of molecular oxygen and
      NADPH to form NO is reduced. The aim of this work was to evaluate the effects of
      OH-arginine on the contractility of rabbit corpus cavernosum (RCC) and to compare
      the capacities of L-arginine and OH-arginine to enhance NO-mediated responses
      under normoxic and hypoxic conditions and in ageing, as models of defective NO
      production. 2 OH-arginine, but not L-arginine, was able to relax phenylephrine
      contracted rabbit trabecular smooth muscle. OH-arginine-induced relaxation was
      inhibited by the NOS-inhibitor, L-NNA (300 microM), and by the guanylyl cyclase
      inhibitor, ODQ (20 microM), while it was not affected by the cytochrome P450
      oxygenase inhibitor, miconazole (0.1 mM). Administration of OH-arginine, but not
      L-arginine, produced a significant increment of cGMP accumulation in RCC tissue.
      3 Relaxation elicited by OH-arginine (300 microM) was still observed at low
      oxygen tension. The increase of cGMP levels induced by ACh (30 microM) in RCC was
      significantly enhanced by addition of OH-arginine (300 microM) in normoxic
      conditions, as well as under hypoxia, while L-arginine did not alter the effects
      of ACh on cGMP accumulation. 4 Endothelium-dependent and nitrergic nerve-mediated
      relaxations were both significantly reduced in RCC from aged animals (>20-months
      old) when compared with young adult rabbits (5-months-old). Treatment with OH
      arginine (300 microM) significantly potentiated endothelium-dependent and
      neurogenic relaxation in corpus cavernosum from aged rabbits, while L-arginine
      (300 microM) did not have significant effects. 5 Results show that OH-arginine
      promotes NO-mediated relaxation of RCC and potentiates the NO-mediated responses
      induced by stimulation of endogenous NO generation in hypoxic and aged tissues.
      We propose that the use of OH-arginine could be of interest in the treatment of
      erectile dysfunction, at least in those secondary to defective NO production.

PMID- 12522075
TI  - Pharmacological characterization of 5-HT(1B) receptor-mediated inhibition of
      local excitatory synaptic transmission in the CA1 region of rat hippocampus.
AB  - 1 In the hippocampus, axon collaterals of CA1 pyramidal cells project locally
      onto neighbouring CA1 pyramidal cells and interneurones, forming a local
      excitatory network which, in disinhibited conditions, feeds polysynaptic epscs
      (poly-epscs). 5-hydroxytryptamine (5-HT) has been shown to inhibit poly-epscs
      through activation of a presynaptic receptor. The aim of the present work was the
      pharmacological characterization of the 5-HT receptor involved in this 5-HT
      action. 2 Poly-epscs, evoked by electrical stimulation of the stratum radiatum
      and recorded in whole-cell voltage-clamp from CA1 pyramidal neurones, were
      studied in mini-slices of the CA1 region under pharmacological block of GABA(A),
      GABA(B), and 5-HT(1A) receptors. 3 The 5-HT(1B) receptor selective agonist 1,4
      dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one
      dihydrochloride (CP 93129) inhibited poly-epscs (EC(50)=55 nM), an effect
      mimicked by the 5-HT(1B) ligands 5-carboxamidotryptamine (5-CT; EC(50)=14 nM) and
      methylergometrine (EC(50)=78 nM), but not by 1-(3-chlorophenyl)piperazine
      dihydrochloride (mCPP; 10 micro M) or 7-trifluoromethyl-4(4-methyl-1-piperazinyl)
      pyrrolo[1,2-a]quinoxaline dimaleate (CGS 12066B; 10 micro M). 4 The effects of CP
      93129 and 5-CT were blocked by the selective 5-HT(1B) receptor antagonist 3-[3
      (dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide
      dihydrochloride (GR 55562; K(B) approximately 100 nM) and by cyanopindolol
      (K(B)=6 nM); methiothepin (10 micro M) and dihydroergotamine (1 micro M). For
      both GR 55562 and methiothepin, application times of at least two hours were
      required in order to achieve their full antagonistic effects. 5 Our results
      demonstrate that 5-HT(1B) receptors are responsible for the presynaptic
      inhibition of neurotransmission at CA1/CA1 local excitatory synapses exerted by 5
      HT.

PMID- 12522076
TI  - Parathyroid hormone increases the sensitivity of inositol trisphosphate receptors
      by a mechanism that is independent of cyclic AMP.
AB  - 1 In fura 2-loaded HEK-293 cells stably expressing human type 1 parathyroid
      hormone (PTH) receptors, PTH potentiated the Ca(2+) mobilization evoked by
      carbachol by >4 fold without itself increasing the intracellular [Ca(2+)]. 2 PTH
      potentiated the Ca(2+) release evoked by a cell-permeant analogue of inositol
      1,4,5-trisphosphate (InsP(3)BM). 3 Prolonged incubation with InsP(3)BM emptied
      the Ca(2+) stores as effectively as PTH in combination with a maximal
      concentration of carbachol, indicating that PTH did not increase the size of the
      InsP(3)-sensitive Ca(2+) pool. 4 Responses to PTH were unaffected by disruption
      of the cytoskeleton. 5 The EC(50) for carbachol-evoked Ca(2+) release and InsP(3)
      formation were indistinguishable (approximately 40 microM), consistent with even
      the highest concentrations of carbachol generating insufficient InsP(3) to
      release the entire InsP(3)-sensitive Ca(2+) pool. 6 Inhibition of cyclic AMP
      dependent protein kinase A (PKA), using H89 or CMIQ, did not affect potentiation
      of carbachol-evoked Ca(2+) signals by PTH. 7 SQ22536 or DDA, inhibitors of
      adenylyl cyclase, inhibited PTH-evoked cyclic AMP formation and IBMX, an
      inhibitor of cyclic nucleotide phosphodiesterase, increased the amount of cyclic
      AMP detected after stimulation by PTH. None of these drugs affected the
      potentiation of Ca(2+) signals by maximal or submaximal concentrations of PTH. 8
      We conclude that PTH potentiates the Ca(2+) release evoked by receptors that
      stimulate InsP(3) formation by sensitizing InsP(3) receptors through a cyclic AMP
      independent mechanism.

PMID- 12522077
TI  - Pharmacological profiles of presynaptic nociceptin/orphanin FQ receptors
      modulating 5-hydroxytryptamine and noradrenaline release in the rat neocortex.
AB  - 1 The pharmacological profiles of presynaptic nociceptin/orphanin FQ (N/OFQ)
      peptide receptors (NOP) modulating 5-hydroxytryptamine (5-HT) and noradrenaline
      (NE) release in the rat neocortex were characterized in a preparation of
      superfused synaptosomes challenged with 10 mM KCl. 2 N/OFQ concentration
      dependently inhibited K(+)-evoked [(3)H]-5-HT and [(3)H]-NE overflow with similar
      potency (pEC(50) approximately 7.9 and approximately 7.7, respectively) and
      efficacy (maximal inhibition approximately 40%). 3 N/OFQ (0.1 micro M) inhibition
      of [(3)H]-5-HT and [(3)H]-NE overflow was antagonized by selective NOP receptor
      antagonists of peptide ([Nphe(1)]N/OFQ(1-13)NH(2) and UFP-101; 10 and 1 microM,
      respectively) and non-peptide (J-113397 and JTC-801; both 0.1 microM) nature.
      Antagonists were routinely applied 3 min before N/OFQ. However, a 21 min pre
      application time was necessary for J-113397 and JTC-801 to prevent N/OFQ
      inhibition of [(3)H]-NE overflow. 4 The NOP receptor ligand [Phe(1)psi(CH(2)
      NH)Gly(2)]N/OFQ(1-13)NH(2) ([F/G]N/OFQ(1-13)NH(2); 3 microM) did not affect K(+)
      evoked [(3)H]-NE but inhibited K(+)-evoked [(3)H]-5-HT overflow in a UFP-101
      sensitive manner. [F/G]N/OFQ(1-13)NH(2) antagonized N/OFQ actions on both
      neurotransmitters. 5 The time-dependency of JTC-801 action was studied in CHO
      cells expressing human NOP receptors. N/OFQ inhibited forskolin-stimulated cAMP
      accumulation and JTC-801, tested at different concentrations (0.1-10 microM) and
      pre-incubation times (0, 40 and 90 min), antagonized this effect in a time
      dependent manner. The Schild-type analysis excluded a competitive type of
      antagonism. 6 We conclude that presynaptic NO receptors inhibiting 5-HT and NE
      release in the rat neocortex have similar pharmacological profiles. Nevertheless,
      they can be differentiated pharmacologically on the basis of responsiveness to
      [F/G]N/OFQ(1-13)NH(2) and time-dependent sensitivity towards non-peptide
      antagonists.

PMID- 12522078
TI  - Evidence against beta 3-adrenoceptors or low affinity state of beta 1
      adrenoceptors mediating relaxation in rat isolated aorta.
AB  - 1 The presence of beta(3)-adrenoceptors and the low affinity state of the beta(1)
      adrenoceptor (formerly "putative beta(4)-adrenoceptor") was investigated in ring
      preparations of rat isolated aorta preconstricted with phenylephrine or
      prostaglandin F(2alpha) (PGF(2alpha)). Relaxant responses to isoprenaline,
      selective beta(3)-adrenoceptor agonists (BRL 37344, SR 58611A, CL 316243) and non
      conventional partial agonists (CGP 12177A, cyanopindolol, pindolol) were
      obtained. 2 In phenylephrine-constricted, but not PGF(2alpha)-constricted rings,
      relaxations to isoprenaline showed a propranolol-resistant component. 3 In
      phenylephrine-constricted rings, relaxations to BRL 37344 (pEC(50), 4.64) and SR
      58611A (pEC(50), 4.94) were not antagonized by the selective beta(3)-adrenoceptor
      antagonist SR 59230A (< or =1 microM). CL 316243 (< or =100 microM) failed to
      produce relaxation. In PGF(2alpha)-constricted rings only SR 58611A produced
      relaxation, which was not affected by SR 59230A (< or =3 microM). 4 Non
      conventional partial agonists produced relaxation in phenylephrine-constricted
      but not PGF(2alpha)-constricted rings. The relaxation to CGP 12177A was
      unaffected by SR 59230A (< or =1 microM) or by CGP 20712A (10 microM), reported
      to block the low affinity state of the beta(1)-adrenoceptor. 5 beta-adrenoceptor
      antagonists also produced relaxation in phenylephrine-constricted rings with an
      order of potency of (pEC(50) values): bupranolol (5.5) approximately 38;SR 59230A
      (5.47) approximately 38;cyanopindolol (5.47)>pindolol (5.30)>alprenolol
      (5.10)>propranolol (4.83)>ICI 118551 (4.60)>CGP 12177A (4.38) approximately
      38;CGP 20712A (4.35). Bupranolol (100 microM), alprenolol (30 microM),
      propranolol (100 microM) and SR 59230A (10 microM) produced no relaxation in
      PGF(2alpha)-constricted rings. 6 These results provide no evidence for the
      presence of functional beta(3)-adrenoceptors or the low affinity state of the
      beta(1)-adrenoceptor in rat aorta.

PMID- 12522079
TI  - Alpha 2 adrenoceptor-mediated vasoconstriction in porcine palmar lateral vein:
      role of phosphatidylinositol 3-kinase and EGF receptor transactivation.
AB  - 1 Alpha(2) adrenoceptors cause vasoconstriction in the porcine palmar lateral
      vein through a mechanism involving the ERK signal transduction cascade, calcium
      influx, and a Src tyrosine kinase. The aim of the present study was to determine
      if phosphatidylinositol 3-kinase (PI 3-kinase) and/or epidermal growth factor
      (EGF) receptor transactivation are also involved. 2 alpha(2) Adrenoceptor
      mediated vasoconstriction and ERK2 activation in the porcine palmar lateral vein
      was inhibited in the presence of either the PI 3-kinase inhibitor LY294002, or
      the EGF receptor tyrosine kinase inhibitor AG1478 suggesting the involvement of
      both PI 3-kinase and EGF receptor transactivation. 3 Akt phosphorylation was
      increased in segments of porcine palmar lateral vein contracted with UK14304
      indicating an increase in Akt activation. This is a further indication that PI 3
      kinase is involved in alpha(2) adrenoceptor-mediated vasoconstriction. Akt
      activation was inhibited by the Src tyrosine kinase inhibitor PP2, and removal of
      extracellular calcium. 4 UK14304 (10 microM) stimulated an increase in
      intracellular calcium in segments of palmar lateral vein. This was inhibited by
      removal of extracellular calcium, but not by nifedipine suggesting the rise in
      calcium is due to influx of calcium through non-L type calcium channels. The
      increase in calcium was also inhibited by LY294002 indicating that PI 3-kinase is
      upstream of calcium influx. 5 These data indicate that alpha(2) adrenoceptor
      mediated vasoconstriction in the porcine palmar lateral vein is dependent upon
      stimulation of PI 3-kinase, leading to an influx of calcium. This results in
      activation of the EGF receptor tyrosine kinase, and finally activation of ERK-MAP
      kinase.

PMID- 12522080
TI  - Restoration of chronic-Delta 9-THC-induced decline in sexuality in male rats by a
      novel benzoflavone moiety from Passiflora incarnata Linn.
AB  - 1 The present study comprised treatment of healthy male rats with Delta(9)
      tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with
      benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora
      incarnata Linneaus, over a period of 30 days. 2 Upon 30-days chronic
      administrations, the THC-treated male rats had a significant loss of libido
      (mounting behaviour with non-oestrous female rats), decrease in sperm count, and
      number of impregnated pro-estrous female rats. 3 Co-administration of BZF (10 and
      20 mg kg(-1) p.o.) afforded significant protection against the chronic-THC
      induced decrease in libido, mating performance and fertility during 30-day
      experimental regimen. The 20 mg kg(-1) dose of BZF exhibited better results. 4
      Upon discontinuation of THC, treatment with BZF (10 and 20 mg kg(-1) p.o.) also
      facilitated the early restoration chronic-THC-induced decline in libido, sperm
      count and sexual fertility within 7 days.

PMID- 12522081
TI  - Unproductive cleavage and the inactivation of protease-activated receptor-1 by
      trypsin in vascular endothelial cells.
AB  - 1 Using fura-2 fluorometry of [Ca(2+)](i) in response to thrombin, trypsin and
      protease-activated receptor activating peptides (PAR-APs), we determined whether
      trypsin cleaves protease-activated receptor 1 (PAR1) and activates it in the
      endothelial cells of the porcine aortic valves and human umbilical vein. 2 Once
      stimulated with thrombin, the subsequent application of trypsin induced a
      [Ca(2+)](i) elevation similar to that obtained without the preceding stimulation
      with thrombin in the valvular endothelial cells. However, the preceding
      stimulation with trypsin abolished the subsequent response to thrombin, but not
      to bradykinin or substance P. 3 The response to PAR1-AP (SFLLRNP) was
      significantly (P<0.05) reduced by the preceding stimulation with thrombin and
      PAR1-AP in the valvular endothelial cells, while, importantly, it remained
      unaffected by the preceding stimulation with either trypsin or PAR2-AP (SLIGRL).
      The response to PAR2-AP was reduced by the preceding stimulation with trypsin and
      PAP2-AP. PAR1-AP attenuated the subsequent responses not only to thrombin and
      PAR1-AP but also to trypsin and PAR2-AP, while PAR2-AP specifically attenuated
      the subsequent responses to trypsin and PAR2-AP. 4 In human umbilical vein
      endothelial cells, a higher affinity PAR1-AP (haPAR1-AP) (Ala-pF-Arg-Cha-HArg-Tyr
      NH(2)) specifically attenuated the responses to thrombin but not trypsin. On the
      other hand, the response to haPAR1-AP was significantly (P<0.05) attenuated by
      the preceding stimulation with thrombin but not trypsin. 5 In conclusion, trypsin
      cleaved PAR1 but did not activate it in the endothelial cells. Moreover, the
      trypsin-cleaved PAR1 was no longer responsive to thrombin.

PMID- 12522082
TI  - Interaction between cysteines introduced into each transmembrane domain of the
      rat P2X2 receptor.
AB  - 1 ATP-gated ion channels (P2X receptors) contain two hydrophobic segments that
      are presumed to span the plasma membrane (TM1 and TM2). Pairs of cysteines were
      introduced by mutagenesis into the rat P2X(2) receptor, one in TM1 one in TM2, at
      positions where single substitutions have previously been shown to confer
      sensitivity to methanethiosulfonates. The receptors were expressed in HEK293
      cells; interactions between the cysteines were sought by measuring the effects on
      ionic currents of dithiothreitol and methanethiosulfonates. 2 Nine pairs gave
      normally functioning channels: F44C/I328C, F44C/N333C, F44C/L338C, Q37C/I328C,
      Q37C/N333C, Q37C/T336C, Q37C/L338C, G30C/I328C, G30C/N333C. None formed
      functionally detectable disulfide bonds. 3 Currents at the F44C/L338C receptor
      had time course and ATP-sensitivity similar to those for the F44C mutation alone.
      Methyl-methanethiosulfonate bound to L338C but did not inhibit ionic current.
      Methyl-methanethiosulfonate inhibited currents at F44C, but not at F44C/L338C. 4
      Ethylammonium-methylthiosulfonate inhibited currents at both F44C and L338C, but
      not at F44C/L338C. It reversed the rapid current deactivation at F44C/L338C. 5
      The results suggest that a methanethiosulfonate binding to L338C prevents binding
      to F44C; this might indicate proximity of these two residues.

PMID- 12522083
TI  - Characterization of the 5-hydroxytryptamine receptors mediating contraction in
      the pig isolated intravesical ureter.
AB  - 1 This study was designed to investigate the effect of 5-hydroxytryptamine (5-HT)
      and to characterize the 5-HT receptors involved in 5-HT responses in the pig
      intravesical ureter. 2 5-HT (0.01-10 microM) concentration-dependently increased
      the tone of intravesical ureteral strips, whereas the increases in phasic
      contractions were concentration-independent. The 5-HT(2) receptor agonist alpha
      methyl 5-HT, mimicked the effect on tone whereas weak or no response was obtained
      with 5-CT, 8-OH-DPAT, m-chlorophenylbiguanide and RS 67333, 5-HT(1), 5-HT(1A), 5
      HT(3) and 5-HT(4) receptor agonists, respectively. 5-HT did not induce relaxation
      of U46619-contracted ureteral preparations. Pargyline (100 microM), a
      monoaminooxidase A/B activity inhibitor, produced leftward displacements of the
      concentration-response curves for 5-HT. 3 5-HT-induced tone was reduced by the 5
      HT(2) and 5-HT(2A) receptor antagonists ritanserine (0.1 microM) and spiperone
      (0.2 microM), respectively. However, 5-HT contraction was not antagonized by
      cyanopindolol (2 microM), SDZ-SER 082 (1 microM), Y-25130 (1 microM) and GR
      113808 (0.1 microM), which are respectively, 5-HT(1A/1B), 5-HT(2B/2C), 5-HT(3),
      and 5-HT(4) selective receptor antagonists. 4 Removal of the urothelium did not
      modify 5-HT-induced contractions. Blockade of neuronal voltage-activated sodium
      channels, alpha-adrenergic receptors and adrenergic neurotransmission with
      tetrodotoxin (1 microM), phentolamine (0.3 microM) and guanethidine (10 microM),
      respectively, reduced the contractions to 5-HT. However, physostigmine (1
      microM), atropine (0.1 microM) and suramin (30 microM), inhibitors of
      cholinesterase activity, muscarinic- and purinergic P(2)-receptors, respectively,
      failed to modify the contractions to 5-HT. 5 These results suggest that 5-HT
      increases the tone of the pig intravesical ureter through 5-HT(2A) receptors
      located at the smooth muscle. Part of the 5-HT contraction is indirectly mediated
      via noradrenaline release from sympathetic nerves.

PMID- 12522084
TI  - Adrenergic mechanisms in canine nasal venous systems.
AB  - 1 We investigated the adrenergic mechanisms of the two venous systems that drain
      the nasal mucosa, thereby their exact role in eliciting nasal decongestion. The
      action of endogenously released noradrenaline and exogenous adrenergic agonists
      on different segments of the nasal venous systems, i.e. collecting (LCV, SCV) and
      outflow (SPV) veins of posterior venous system, collecting (ACV) and outflow
      (DNV) veins of anterior venous system and venous sinusoids of the septal mucosa
      (SM), were studied. In vitro isometric tension of the vascular segments was
      measured. 2 Transmural nerve stimulation (TNS) produced constriction in ACV, DNV
      and SM, primary constriction followed by secondary dilatation in LCV and SCV and
      dilatation in SPV. Tetrodotoxin (10(-6) M) abolished all responses. Phentolamine
      (10(-6) M), prazosin (10(-6) M) and rauwolscine (10(-7) M) inhibited the
      constriction in all venous vessels. Propranolol (10(-6) M), atenolol (10(-6) M)
      and ICI 118,551 (10(-6) M) inhibited the relaxation in SPV but not in LCV and
      SCV. Phenylephrine and clonidine constricted whereas dobutamine and terbutaline
      relaxed all venous vessels dose-dependently. 3 These results indicate alpha(1)-,
      alpha(2)-, beta(1)- and beta(2)-adrenoceptors are present in both venous systems.
      TNS causes constriction of anterior venous system, venous sinusoids and posterior
      collecting veins primarily via postjunctional alpha(2)-adrenoceptors but
      relaxation of posterior outflow vein equally via postjunctional beta(1)- and
      beta(2)-adrenoceptors. The combined action of the two adrenergic mechanisms can
      reduce nasal airway resistance in vivo by decreasing vascular capacitance and
      enhancing venous drainage via the posterior venous system.

PMID- 12522085
TI  - Demonstration of functional M3-muscarinic receptors in ventricular cardiomyocytes
      of adult rats.
AB  - 1 Muscarinic receptors (M-receptors) in the mammalian heart are predominantly of
      the M(2)-subtype. The aim of this study was to find out whether there might exist
      an additional myocardial non-M(2)-receptor. 2 For this purpose, we assessed, in
      adult rat isolated ventricular cardiomyocytes, carbachol-induced [(3)H]-inositol
      phosphate (IP) formation, and its inhibition by M-receptor antagonists. 3
      Carbachol (10(-7)-10(-3) mol l(-1)) increased IP-formation (maximal increase:
      14+/-3% above basal, n=6). This increase was significantly enhanced by
      pretreatment with pertussis toxin (PTX, 250 ng ml(-1) for 20 h): maximal increase
      was 31+/-5%, pEC(50)-value was 5.08+/-0.33 (n=6). 4 In PTX-pretreated
      cardiomyocytes 100 micromol l(-1) carbachol-induced IP-formation was inhibited by
      atropine (pK(i)-value: 8.89+/-0.10) and by the M(3)-receptor antagonist
      darifenacin (pK(i)-value: 8.67+/-0.23) but was not significantly affected by the
      M(1)-receptor antagonist pirenzepine (1 micromol l(-1)) or the M(2)-receptor
      antagonists AF-DX 116 and himbacine (1 micromol l(-1)). 5 In conclusion, in adult
      rat cardiomyocytes there exists an additional, non-M(2)-receptor, that is coupled
      to activation of the phospholipase C/IP(3)-pathway; this receptor is very likely
      of the M(3)-subtype.

PMID- 12522086
TI  - Inhibition of hEAG1 and hERG1 potassium channels by clofilium and its tertiary
      analogue LY97241.
AB  - 1 We investigated the inhibition of hEAG1 potassium channels, expressed in
      mammalian cells and Xenopus oocytes, by several blockers that have previously
      been reported to be blockers of hERG1 channels. 2 In the whole-cell mode of
      mammalian cells, LY97241 was shown to be a potent inhibitor of both hEAG1 and
      hERG1 channels (IC(50) of 4.9 and 2.2 nM, respectively). Clofilium, E4031, and
      haloperidol apparently inhibited hEAG1 channels with lower potency than hERG1
      channels, but they cannot be considered hERG1-specific. 3 The block of hEAG1
      channels by LY97241 and clofilium was time-, use-, and voltage-dependent, best
      explained by an open-channel block mechanism. 4 Both drugs apparently bind from
      the intracellular side of the membrane at (a) specific site(s) within the central
      cavity of the channel pore. They can be trapped by closure of the activation
      gate. 5 In inside-out patches from Xenopus oocytes, hEAG1 block by clofilium was
      stronger than by LY97241 (IC(50) of 0.8 and 1.9 nM, respectively). In addition,
      hEAG1 block by clofilium was much faster than by LY97241 although there was no
      difference in the voltage dependence of the on-rate of block. 6 Physico-chemical
      differences of clofilium and the weak base LY97241 determine the access of the
      drugs to the binding site and thereby the influence of the recording mode on the
      apparent block potencies. This phenomenon must be considered when assessing the
      inhibitory action of drugs on ion channels.

PMID- 12522087
TI  - Activation of vanilloid receptor 1 by resiniferatoxin mobilizes calcium from
      inositol 1,4,5-trisphosphate-sensitive stores.
AB  - 1 Capsaicin and resiniferatoxin (RTX) stimulate Ca2+ influx by activating
      vanilloid receptor 1 (VR1), a ligand-gated Ca2+ channel on sensory neurones. We
      investigated whether VR1 activation could also trigger Ca2+ mobilization from
      intracellular Ca2+ stores. 2 Human VR1-transfected HEK293 cells (hVR1-HEK293)
      were loaded with Fluo-3 or a mixture of Fluo-4 and Fura Red and imaged on a
      fluorometric imaging plate reader (FLIPR) and confocal microscope respectively. 3
      In Ca2+ -free media, RTX caused a transient elevation in intracellular free Ca2+
      concentration in hVR1-HEK293 cells (pEC(50) 6.45+/-0.05) but not in wild type
      cells. Capsaicin (100 microM) did not cause Ca2+ mobilization under these
      conditions. 4 RTX-mediated Ca2+ mobilization was inhibited by the VR1 receptor
      antagonist capsazepine (pIC(50) 5.84+/-0.04), the Ca2+ pump inhibitor
      thapsigargin (pIC(50) 7.77+/-0.04), the phospholipase C inhibitor U-73122
      (pIC(50) 5.35+/-0.05) and by depletion of inositol 1,4,5-trisphosphate-sensitive
      Ca2+ stores by pretreatment with the acetylcholine-receptor agonist carbachol (20
      microM, 2 min). These data suggest that RTX causes Ca2+ mobilization from
      inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in hVR1-HEK293 cells. 5 In the
      presence of extracellular Ca2+, both capsaicin-mediated and RTX-mediated Ca2+
      rises were attenuated by U-73122 (10 microM, 30 min) and thapsigargin (1 microM,
      30 min). We conclude that VR1 is able to couple to Ca2+ mobilization by a Ca2+
      dependent mechanism, mediated by capsaicin and RTX, and a Ca2+ independent
      mechanism mediated by RTX alone.

PMID- 12522088
TI  - Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter
      release at normal and acetylcholinesterase knockout mouse neuromuscular
      junctions.
AB  - 1 The present study was performed to evaluate the presence and the physiological
      consequences of butyrylcholinesterase (BChE) inhibition on isolated phrenic
      hemidiaphragm preparations from normal mice expressing acetylcholinesterase
      (AChE) and BChE, and from AChE-knockout mice (AChE(-/-)) expressing only BChE. 2
      Histochemical and enzymatic assays revealed abundance of AChE and BChE in normal
      mature neuromuscular junctions (NMJs). 3 In normal NMJs, in which release was
      reduced by low Ca(2+)/high Mg(2+) medium BChE inhibition with
      tetraisopropylpyrophosphoramide (iso-OMPA) or bambuterol decreased (
      approximately 50%) evoked quantal release, while inhibition of AChE with
      fasciculin-1, galanthamine (10, 20 micro M) or neostigmine (0.1-1 micro M)
      increased (50-80%) evoked quantal release. Inhibition of both AChE and BChE with
      galanthamine (80 micro M), neostigmine (3-10 micro M), O-ethylS-2
      (diisopropylamino)ethyl-methylphosphono-thioate (MTP) or phospholine decreased
      evoked transmitter release (20-50%). 4 In AChE(-/-) NMJs, iso-OMPA pre-treatment
      decreased evoked release. 5 Muscarinic toxin-3 decreased evoked release in both
      AChE(-/-) and normal NMJs treated with low concentrations of neostigmine,
      galanthamine or fasciculin-1, but had no effect in normal NMJs pretreated with
      iso-OMPA, bambuterol, MTP and phospholine. 6 In normal and AChE(-/-) NMJs
      pretreatment with iso-OMPA failed to affect the time course of miniature endplate
      potentials and full-sized endplate potentials. 7 Overall, our results suggest
      that inhibition or absence of AChE increases evoked quantal release by involving
      muscarinic receptors (mAChRs), while BChE inhibition decreases release through
      direct or indirect mechanisms not involving mAChRs. BChE apparently is not
      implicated in limiting the duration of acetylcholine action on postsynaptic
      receptors, but is involved in a presynaptic modulatory step of the release
      process.

PMID- 12522089
TI  - In vitro evidence for the presence of [3H]-haloperidol uptake in rat brain.
AB  - 1 The neuroleptic [(3)H]-haloperidol (HP) was taken up in synaptosomes prepared
      from rat brain, in a temperature-, sodium ion-, and energy-dependent process. 2
      The highest concentration of uptake sites (V(max)=2.37 pmol mg(-1) protein min(
      1)) was in the striatum with the other brain areas displaying lower (by 50-70%)
      values. 3 The affinity values (K(m) approximately equal to 40 nM) were similar in
      all brain areas considered. 4 The pharmacological characterization did not
      indicate a well-defined group of inhibitors, which suggested that HP might not
      use a transporter for recognized neurotransmitters. 5 The HP metabolites tested,
      including HPTP, were competitive inhibitors of [(3)H]-HP uptake, an indirect
      indication that they may actively enter the striatal nerve endings through the
      same carrier. 6 Since the uptake process was partially affected by the incubation
      of [(3)H]-HP in the presence of several antagonists of HP-transforming cytochrome
      P450 isoforms, the binding of HP at some enzyme sites inside the synaptosome
      cannot be excluded. 7 In conclusion, the present results suggest that HP may be
      actively transported in the rat brain.

PMID- 12522090
TI  - Effector mechanism of magnolol-induced apoptosis in human lung squamous carcinoma
      CH27 cells.
AB  - 1 Magnolol, an active component isolated from the root and stem bark of Magnolia
      officinalis, has been reported to exhibit antitumour effects, but little is known
      about its molecular mechanisms of action. 2 Magnolol inhibited proliferation of
      human lung squamous carcinoma CH27 cells at low concentrations (10-40 microM),
      and induced apoptosis at high concentrations (80-100 microM). 3 Treatment with 80
      microM magnolol significantly increased the expression of Bad and Bcl-X(S)
      proteins, whereas it decreased the expression of Bcl-X(L). Overexpression of Bcl
      2 protected CH27 cells against magnolol-triggered apoptosis. 4 Magnolol treatment
      resulted in accumulation of cytosolic cytochrome c and activation of caspase-9
      and downstream caspases (caspase-3 and -6). Pretreatment with z-VAD-fmk markedly
      inhibited magnolol-induced cell death, but did not prevent cytosolic cytochrome c
      accumulation. 5 Magnolol induced a modest and persistent JNK activation and ERK
      inactivation in CH27 cells without evident changes in the protein levels. The
      responsiveness of JNK and ERK to magnolol suggests the involvement of these
      kinases in the initiation of the apoptosis process. 6 These results indicate that
      regulation of the Bcl-2 family, accumulation of cytosolic cytochrome c, and
      activation of caspase-9 and caspase-3 may be the effector mechanisms of magnolol
      induced apoptosis.

PMID- 12522091
TI  - Nitric oxide enhances substance P-induced itch-associated responses in mice.
AB  - 1 Substance P (SP) elicits itch and itch-associated responses in humans and mice,
      respectively. In mice, NK(1) tachykinin receptors are involved in SP-induced itch
      associated responses, scratching, and mast cells do not play a critical role. The
      present study was conducted to elucidate the role of nitric oxide (NO) on SP
      induced scratching in mice. 2 An intradermal injection of SP (100 nmol site(-1))
      elicited scratching in mice, and it was suppressed by an intravenous injection of
      the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), but
      not by its inactive enantiomer D-NAME. Intradermal injections of L-NAME (100 nmol
      site(-1)), another NOS inhibitor 7-nitroindazole (10 nmol site(-1)) and the NO
      scavenger haemoglobin (0.01-10 nmol site(-1)) also inhibited SP-induced
      scratching. 3 L-NAME (100 nmol site(-1)) did not affect scratching induced by an
      intradermal injection of 5-hydroxytryptamine (100 nmol site(-1)). 4 Intradermal
      injections of L-arginine (300 nmol site(-1)) and the NO donor (+/-)-(E)-4-ethyl-2
      [(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3; 100 nmol site(-1)) increased
      scratching induced by SP. Intradermal injections of L-arginine (1-1000 nmol site(
      1)) or NOR3 (1-100 nmol site(-1)) alone were without effects on scratching. 5
      Intradermal injections of SP (10-100 nmol site(-1)) increased the intradermal
      concentration of NO in a dose-dependent manner in mice. An increase in NO levels
      induced by SP was inhibited by L-NAME and the NK(1) tachykinin receptor
      antagonist L-668,169, but not by the NK(2) tachykinin receptor antagonist L
      659,877. 6 SP (1-10 micro M) elicited NO production in cultured human
      keratinocytes and the SP-induced NO production was inhibited by L-NAME and L
      668,169. 7 We conclude that intradermal SP increases NO in the skin, possibly
      through the action on NK(1) tachykinin receptors on the epidermal keratinocytes
      and that NO enhances SP-induced itch-associated responses.

PMID- 12522092
TI  - Pertussis toxin sensitive and insensitive effects of adenosine and carbachol in
      murine atria overexpressing A(1)-adenosine receptors.
AB  - 1 It was investigated how A(1)-adenosine receptor overexpression alters the
      effects of carbachol on force of contraction and beating rate in isolated murine
      atria. Moreover, the influence of pertussis toxin on the inotropic and
      chronotropic effects of adenosine and carbachol in A(1)-adenosine receptor
      overexpressing atria was studied. 2 Adenosine and carbachol alone exerted
      negative inotropic and chronotropic effects in electrically driven left atrium or
      spontaneously beating right atrium of wild-type mice. 3 These effects were
      abolished or reversed by pre-treatment of animals with pertussis toxin which can
      interfere with signal transduction through G-proteins. 4 Adenosine and carbachol
      exerted positive inotropic but negative chronotropic effects in atrium
      overexpressing A(1)-adenosine receptors from transgenic mice. 5 The positive
      inotropic effects of adenosine and carbachol were qualitatively unaltered whereas
      the negative chronotropic effects were abolished or reversed in atrium
      overexpressing A(1)-adenosine receptors after pre-treatment by pertussis toxin. 6
      Qualitatively similar effects for adenosine and carbachol were noted in the
      presence of isoprenaline, beta-adrenoceptor agonist. 7 It is concluded that
      overexpression of A(1)-adenosine receptors also affects the signal transduction
      of other heptahelical, G-protein coupled receptors like the M-cholinoceptor in
      the heart. The chronotropic but not the inotropic effects of adenosine and
      carbachol in transgenic atrium were mediated via pertussis toxin sensitive G
      proteins.

PMID- 12522093
TI  - Alpha 1-adrenoceptor effects mediated by protein kinase C alpha in human cultured
      prostatic stromal cells.
AB  - 1 We have investigated the effects of alpha(1)-adrenoceptor stimulation upon
      contractility, Ca(2+) influx, inositol phosphate production, and protein kinase C
      (PKC) translocation in human cultured prostatic stromal cells (HCPSC). 2 The
      alpha(1)-adrenoceptor selective agonist phenylephrine elicited contractile
      responses of HCPSC, i.e. a maximal cell shortening of 45+/-6% of initial cell
      length, with an EC(50) of 1.6+/-0.1 microM. The alpha(1)-adrenoceptor selective
      antagonists prazosin (1 microM) and terazosin (1 microM) both blocked
      contractions to phenylephrine (10 microM). The L-type calcium channel blocker
      nifedipine (10 microM), and the PKC inhibitors Go 6976 (1 microM) and
      bisindolylmaleimide (1 microM) also inhibited phenylephrine-induced contractions.
      3 Phenylephrine caused a concentration dependent increase in inositol phosphate
      production (EC(50) 119+/-67 nM). This response was blocked by terazosin (1
      microM). 4 Phenylephrine caused the translocation of the PKC alpha isoform, but
      not the beta, delta, gamma, epsilon or lambda isoforms, from the cytosolic to the
      particulate fraction of HCPSC, with an EC(50) of 5.7+/-0.5 microM. 5 In FURA-2AM
      (5 microM) loaded cells, phenylephrine elicited concentration dependent increases
      in [Ca(2+)](i), with an EC(50) of 3.9+/-0.4 microM. The response to phenylephrine
      (10 microM) was blocked by prazosin (1 microM), bisindolymaleimide (1 microM),
      and nifedipine (10 microM). 6 In conclusion, this study has shown that HCPSC
      express functional alpha(1)-adrenoceptors, and that the intracellular pathways
      responsible for contractility may be largely dependent upon protein kinase C
      activation and subsequent opening of L-type calcium channels.

PMID- 12522094
TI  - Bradykinin inhibits development of myocardial infarction through B2 receptor
      signalling by increment of regional blood flow around the ischaemic lesions in
      rats.
AB  - 1 To identify the roles of endogenous kinins in prevention of myocardial
      infarction (MI), we performed the permanent ligation of coronary artery in rats.
      2 The size of MI 12, 24, and 48 h after coronary ligation in kininogen-deficient
      Brown Norway Katholiek (BN-Ka) rats was significantly larger (49.7+/-0.2%, 49.6+/
      2%, and 51.1+/-1%, respectively) than that of kinin-replete Brown Norway Kitasato
      (BN-Ki) rats (42+/-2%, 38.5+/-4%, and 41.5+/-1%). 3 Hoe140, a bradykinin (BK)
      B(2) receptor antagonist injected (1.0 mg kg(-1), i.v.) half an hour before, and
      every 8 h after, coronary ligation, significantly increased the size of MI in
      Sprague-Dawley rats. Aprotinin, a kallikrein inhibitor, which was infused
      intravenously (10,000 Units kg(-1) h(-1)) with an osmotic mini-pump,
      significantly increased the size of an MI 24 h after ligation. 4 When evaluated
      using microspheres, the regional myocardial blood flow around the necrotic lesion
      in BN-Ka rats 6 h after ligation was reduced more than that in BN-Ki rats with MI
      by 41-46%. The same was true in Hoe140-treated BN-Ki rats. 5 FR190997, a
      nonpeptide B(2) agonist, which was infused (10 microg kg(-1) h(-1)) into the vena
      cava of BN-Ka rats for 24 h with an osmotic mini-pump, caused significant
      reduction in the size of MI (38+/-3%), in comparison with the size in vehicle
      solution-treated rats (51+/-3%). The size of MI in FR190997-treated BN-Ka rats
      was the same as in BN-Ki rats. 6 These results suggested that endogenous kinin
      has the capacity to reduce the size of MI via B(2) receptor signalling because of
      the increase in regional myocardial blood flow around the ischaemic lesion.

PMID- 12522095
TI  - Monovalent cation (MC) current in cardiac and smooth muscle cells: regulation by
      intracellular Mg2+ and inhibition by polycations.
AB  - 1 Previously we have described a monovalent cation (MC) current that could be
      unmasked by the removal of extracellular divalent cations in vascular smooth
      muscle cells (SMC) and cardiac myocytes, but specific and potent inhibitors of MC
      current have not been found, and the mechanism of its intracellular regulation
      remains obscure. 2 Here we show that small MC current is present in intact cells
      and could be dramatically up-regulated during cell dialysis. MC current in
      dialyzed cells strongly resembled monovalent cation current attributed to Ca(2+)
      release-activated Ca(2+)-selective (CRAC) channels, but its activation did not
      require depletion of Ca(2+) stores, and was observed when the cells were dialyzed
      with, or without BAPTA. 3 Intracellular free Mg(2+) inhibits MC current with
      K(d)=250 microM. 4 Extracellular (but not intracellular) spermine effectively
      blocked MC current with K(d) =3-10 microM, while store-operated cations (SOC)
      channels and capacitative Ca(2+) influx were not affected. 5 Spermine effectively
      inhibited MC current-induced SMC depolarization, and prevented Ca(2+) paradox
      induced vascular contracture. 6 Both, MC and SOC currents were inhibited by 2
      aminoethoxydiphenyl borate (2-APB). 7 It is concluded that MC current could be
      regulated by intracellular Mg(2+), and low concentrations of extracellular
      spermine could be used to discriminate it from SOC current, and to assess its
      role in cellular function.

PMID- 12522096
TI  - 5-hydroxyindole causes convulsions and increases transmitter release in the CA1
      region of the rat hippocampus.
AB  - 1 5-hydroxyindole (5-OHi) is a proposed tryptophan metabolite able to cause
      convulsions when systemically injected into rodents. We studied its effects using
      microdialysis in vivo and electrophysiological approaches in vitro. 2 Local
      administration of 5-OHi into the CA1 region of the rat hippocampus, via a
      microdialysis probe, significantly increased glutamate concentrations in the
      dialysates. 3 In rat hippocampal slices, using extracellular recordings in the
      CA1 region, 5-OHi (30-300 microM) increased the amplitude of population spikes
      and fEPSPs. 4 In the same preparation, using intracellular recordings in CA1
      pyramidal neurons, 5-OHi reduced the latency of firing induced by direct
      depolarization and increased both evoked excitatory and slow inhibitory
      postsynaptic potential amplitudes, without affecting the resting membrane
      potential, the after-hyperpolarization or the neuronal input resistance. It also
      altered GABA(A)-mediated neurotransmission by increasing the frequency and the
      amplitude of pharmacologically isolated spontaneous inhibitory postsynaptic
      currents (sIPSC). 5 In separate experiments, performed by measuring AMPA or NMDA
      induced depolarization in cortical wedges, 5-OHi did not modify glutamate
      receptor agonist responses. 6 Our results show that 5-OHi causes convulsions,
      modifies the properties and the function of the hippocampal circuitry, and
      facilitates the output of both excitatory and inhibitory transmitters.

PMID- 12522097
TI  - Tachykinin NK3 and NK1 receptor activation elicits secretion from porcine airway
      submucosal glands.
AB  - 1 We presently characterized the tachykinin receptor subtypes, using tachykinin
      receptor agonists and selective antagonists, that induce submucosal gland fluid
      flux (J(G)) from porcine tracheal explants with the hillocks technique. We also
      investigated the effects of the tachykinin receptor agonists on the
      electrophysiologic parameters of the tracheal epithelium in Ussing chambers. 2
      The NK(1) tachykinin receptor agonist substance P (SP, 1 microM) and the NK(3)
      tachykinin receptor agonist [MePhe(7)]neurokinin B ([MePhe(7)]NKB, 1 microM)
      induced gland fluid fluxes of 0.29+/-0.03 microl min(-1) cm(-2) (n=26) and 0.36+/
      0.05 microl min(-1) cm(-2) (n=24), respectively; while the NK(2) tachykinin
      receptor agonist [betaAla(8)]neurokinin A (4-10) ([betaAla(8)]NKA (4-10), 1
      microM) had no effect on J(G) (n=10). 3 The NK(1) receptor antagonist CP99994 (1
      microM, n=9) blocked 93% of the SP-induced J(G), whereas the NK(3) receptor
      antagonist SB223412 (1 microM, n=12) had no effect on the SP-induced J(G).
      However, SB223412 (1 microM, n=9) blocked 89% of the [MePhe(7)]NKB-induced J(G)
      while CP99994 (1 microM, n=10) did not affect the [MePhe(7)]NKB-induced J(G). The
      NK(2) receptor antagonist SR48968 (1 microM) did not block the J(G) induced by
      either the NK(1) (n=4) or NK(3) (n=13) receptor agonists. 4 The nicotinic
      ganglionic acetylcholine receptor antagonist hexamethonium (1 microM) and the
      muscarinic acetylcholine receptor antagonist atropine (1 microM) also decreased
      the NK(3) receptor agonist-induced J(G) by 67% (n=10) and 71% (n=12),
      respectively. 5 The potential difference (PD), short-circuit current (I(SC)), and
      membrane resistance (R(M)) of the porcine tracheal epithelial membranes were not
      significantly affected by any of the neurokinin agonists or antagonists (1
      microM, basolateral) used in this study, although SP and [betaAla(8)]NKA (4-10)
      induced a slight transient epithelial hyperpolarization. 6 These data suggest
      that NK(1) and NK(3) receptors induce porcine airway gland secretion by different
      mechanisms and that the NK(3) receptor agonists induced secretion is likely due
      to activation of prejunctional NK(3) receptors on parasympathetic nerves,
      resulting in acetylcholine-release. We conclude that tachykinin receptor
      antagonists may have therapeutic potential in diseases with pathophysiological
      mucus hypersecretion such as asthma and chronic bronchitis.

PMID- 12522098
TI  - Comparison of signalling mechanisms involved in rat mesenteric microvessel
      contraction by noradrenaline and sphingosylphosphorylcholine.
AB  - 1 We have compared the signalling mechanisms involved in the pertussis toxin
      sensitive and -insensitive contraction of rat isolated mesenteric microvessels
      elicited by sphingosylphosphorylcholine (SPC) and noradrenaline (NA),
      respectively. 2 The phospholipase D inhibitor butan-1-ol (0.3%), the store
      operated Ca(2+) channel inhibitor SK>F 96,365 (10 microM), the tyrosine kinase
      inhibitor genistein (10 microM), and the src inhibitor PP2 (10 microM) as well as
      the negative controls (0.3% butan-2-ol and 10 microM diadzein and PP3) had only
      little effect against either agonist. 3 Inhibitors of phosphatidylinositol-3
      kinase (wortmannin and LY 294,002, 10 microM each) or of mitogen-activated
      protein kinase kinase (PD 98,059 and U 126, 10 microM each) did not consistently
      attenuate NA- and SPC-induced contraction as compared to their vehicles or
      negative controls (LY 303,511 or U 124). 4 The phospholipase C inhibitor U 73,122
      (10 microM) markedly inhibited the SPC- and NA-induced contraction (70% and 88%
      inhibition of the response to the highest NA and SPC concentration,
      respectively), whereas its negative control U 73,343 (10 microM) caused only less
      than 30% inhibition. 5 The rho-kinase inhibitors Y 27,632 (10 microM) and fasudil
      (30 microM) caused a rightward-shift of the NA concentration-response curve by
      0.7-0.8 log units and reduced the response to 10 microM SPC by 88% and 83%,
      respectively. 6 These data suggest that SPC and NA, while acting on different
      receptors coupling to different G-protein classes, elicit contraction of rat
      mesenteric microvessels by similar signalling pathways including phospholipase C
      and rho-kinase.

PMID- 12522099
TI  - ADP stimulation of inositol phosphates in hepatocytes: role of conversion to ATP
      and stimulation of P2Y2 receptors.
AB  - 1 Accumulation of inositol (poly)phosphates (InsP(x)) has been studied in rat
      hepatocytes labelled with [(3)H]inositol. Stimulation with ADP resulted in a
      significant increase in total [(3)H]InsP(x), whereas 2-MeSADP had only a small
      effect and ADPbetaS was ineffective. UTP and ITP also stimulated substantial
      increases in [(3)H]InsP(x). 2 The dose-response curve to ADP was largely
      unaltered by the presence of the P2Y(1) antagonist, adenosine-3'-phosphate-5'
      phosphate (A3P5P). Similarly, inclusion of MRS 2179, a more selective P2Y(1)
      antagonist, had no effect on the dose-response curve to ADP. 3 The inclusion of
      hexokinase in the assay reduced, but did not abolish, the response to ADP. 4 HPLC
      analysis revealed that ADP in the medium was rapidly converted to AMP and ATP.
      The inclusion of hexokinase removed ATP, but exacerbated the decline in ADP
      concentration, leading to increased levels of AMP. 2-MeSADP was stable in the
      medium and ATP was largely unaffected. 5 The addition of the adenylate kinase
      inhibitor, diadenosine pentaphosphate (Ap(5)A) significantly reduced the ADP
      response. HPLC analysis conducted in parallel demonstrated that this treatment
      inhibited conversion of ADP to ATP and AMP. 6 Inclusion of the P1 antagonist CGS
      15943 had no effect on the dose-response curve to ADP. 7 These observations
      indicate that hepatocytes respond to ADP with an increase in inositol
      (poly)phosphates following conversion to ATP. P2Y(1) activation in hepatocytes
      does not appear to be coupled to inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3))
      production.

PMID- 12522100
TI  - The role of transcriptional corepressor Nif3l1 in early stage of neural
      differentiation via cooperation with Trip15/CSN2.
AB  - Mouse Nif3l1 gene is highly conserved from bacteria to human. Even though this
      gene is expressed throughout embryonic development, its biological function is
      still obscure. Here, we show that Nif3l1 participates in retinoic acid-primed
      neural differentiation of P19 embryonic carcinoma cells through cooperation with
      Trip15/CSN2, a transcriptional corepressor/component of COP9 signalosome. We
      isolated Nif3l1 cDNA from P19 cell cDNA library by a yeast two-hybrid screening
      using Trip15/CSN2 as a bait. This interaction was confirmed by a pull-down assay
      and an epitope-tagged coimmunoprecipitation. Although Nif3l1 was mainly detected
      in the cytoplasm, the translocation of Nif3l1 into the nuclei was observed in
      retinoic acid-primed neural differentiation of P19 cells and enhanced by the
      enforced expression of Trip15/CSN2. Furthermore, enforced expression of sense
      Nif3l1 RNA, but not antisense RNA, enhanced the neural differentiation of P19
      cells accompanying the intense down-regulation of Oct-3/4 mRNA expression and the
      rapid induction of Mash-1 mRNA expression. Luciferase reporter assay showed that
      Nif3l1 could act as a transcriptional repressor and synergized the
      transcriptional repression by Trip15/CSN2. These results indicate that Nif3l1
      implicates in neural differentiation through the cooperation with Trip15/CSN2.

PMID- 12522101
TI  - CrkL directs ASAP1 to peripheral focal adhesions.
AB  - Searching for proteins in platelets that can interact with the N-terminal SH3
      domain of CrkL (using a combination of a pull-down assay followed by mass
      spectrometry), we have found that human platelets express an ADP-ribosylation
      factor (Arf)-specific GTPase-activating protein (GAP), ASAP1, as a CrkL-binding
      protein. In spreading platelets, most endogenous ASAP1 is localized at peripheral
      focal adhesions. To determine the physiologic significance of the CrkL-ASAP1
      association, we overexpressed CrkL, ASAP1, or both in combination in COS7 cells.
      Unlike endogenous ASAP1 in platelets, overexpressed ASAP1 showed diffuse
      cytoplasmic distribution. However, when co-expressed with wild-type CrkL, both
      endogenous and expressed ASAP1 accumulated at CrkL-induced focal adhesions. An
      SH2-mutated CrkL, which cannot localize at focal adhesions, failed to recruit
      ASAP1 into focal adhesions. Thus, CrkL appears to be a lynchpin between ASAP1 and
      peripheral focal adhesions.

PMID- 12522102
TI  - Cellular arachidonate-releasing function of novel classes of secretory
      phospholipase A2s (groups III and XII).
AB  - Here we report cellular arachidonate (AA) release and prostaglandin (PG)
      production by novel classes of secretory phospholipase A(2)s (sPLA(2)s), groups
      III and XII. Human group III sPLA(2) promoted spontaneous AA release, which was
      augmented by interleukin-1, in HEK293 transfectants. The central sPLA(2) domain
      alone was sufficient for its in vitro enzymatic activity and for cellular AA
      release at the plasma membrane, whereas either the unique N- or C-terminal domain
      was required for heparanoid-dependent action on cells to augment AA release,
      cyclooxygenase-2 induction, and PG production. Group III sPLA(2) was
      constitutively expressed in two human cell lines, in which other sPLA(2)s
      exhibited different stimulus inducibility. Human group XII sPLA(2) had a weak
      enzymatic activity in vitro and minimally affects cellular AA release and PG
      production. Cells transfected with group XII sPLA(2) exhibited abnormal
      morphology, suggesting a unique functional aspect of this enzyme. Based on the
      present results as well as our current analyses on the group I/II/V/X sPLA(2)s,
      general properties of cellular actions of a full set of mammalian sPLA(2)s in
      regulating AA metabolism are discussed.

PMID- 12522103
TI  - Association of the kinesin motor KIF1A with the multimodular protein liprin
      alpha.
AB  - Liprin-alpha/SYD-2 is a multimodular scaffolding protein important for
      presynaptic differentiation and postsynaptic targeting of alpha-amino-3-hydroxy-5
      methyl-4-isoxazoleproprionic acid glutamate receptors. However, the molecular
      mechanisms underlying these functions remain largely unknown. Here we report that
      liprin-alpha interacts with the neuron-specific kinesin motor KIF1A. KIF1A
      colocalizes with liprin-alpha in various subcellular regions of neurons. KIF1A
      coaccumulates with liprin-alpha in ligated sciatic nerves. KIF1A cofractionates
      and coimmunopreciptates with liprin-alpha and various liprin-alpha-associated
      membrane, signaling, and scaffolding proteins including alpha-amino-3-hydroxy-5
      methyl-4-isoxazoleproprionic acid receptors, GRIP/ABP, RIM, GIT1, and beta PIX.
      These results suggest that liprin-alpha functions as a KIF1A receptor, linking
      KIF1A to various liprin-alpha-associated proteins for their transport in neurons.

PMID- 12522104
TI  - The transcriptional coactivator PGC-1 regulates the expression and activity of
      the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha).
AB  - The estrogen-related receptor alpha (ERRalpha) is one of the first orphan nuclear
      receptors identified. Still, we know little about the mechanisms that regulate
      its expression and its activity. In this study, we show that the transcriptional
      coactivator PGC-1, which is implicated in the control of energy metabolism,
      regulates ERRalpha at two levels. First, PGC-1 induces the expression of
      ERRalpha. Consistent with this induction, levels of ERRalpha mRNA in vivo are
      highest in PGC-1 expressing tissues, such as heart, kidney, and muscle, and up
      regulated in response to signals that induce PGC-1, such as exposure to cold.
      Second, PGC-1 interacts physically with ERRalpha and enables it to activate
      transcription. Strikingly, we find that PGC-1 converts ERRalpha from a factor
      with little or no transcriptional activity to a potent regulator of gene
      expression, suggesting that ERRalpha is not a constitutively active nuclear
      receptor but rather one that is regulated by protein ligands, such as PGC-1. Our
      findings suggest that the two proteins act in a common pathway to regulate
      processes relating to energy metabolism. In support of this hypothesis,
      adenovirus-mediated delivery of small interfering RNA for ERRalpha, or of PGC-1
      mutants that interact selectively with different types of nuclear receptors,
      shows that PGC-1 can induce the fatty acid oxidation enzyme MCAD (medium-chain
      acyl-coenzyme A dehydrogenase) in an ERRalpha-dependent manner.

PMID- 12522106
TI  - Understanding biological complexity: lessons from the past.
AB  - Advances in molecular biology now permit complex biological systems to be tracked
      at an exquisite level of detail. The information flow is so great, however, that
      using intuition alone to draw connections is unrealistic. Thus, the need to
      integrate mathematical biology with experimental biology is greater than ever. To
      achieve this integration, obstacles that have traditionally prevented effective
      communication between theoreticians and experimentalists must be overcome, so
      that experimentalists learn the language of mathematics and dynamical modeling
      and theorists learn the language of biology. Fifty years ago Alan Hodgkin and
      Andrew Huxley published their quantitative model of the nerve action potential;
      in the same year, Alan Turing published his work on pattern formation in
      activator-inhibitor systems. These classic studies illustrate two ends of the
      spectrum in mathematical biology: the detailed model approach and the minimal
      model approach. When combined, they are highly synergistic in analyzing the
      mechanisms underlying the behavior of complex biological systems. Their effective
      integration will be essential for unraveling the physical basis of the mysteries
      of life.

PMID- 12522105
TI  - Mechanisms of protease-activated receptor-4 actions in cardiomyocytes. Role of
      Src tyrosine kinase.
AB  - Protease-activated receptor (PAR)-4 is a low affinity thrombin receptor with slow
      activation and desensitization kinetics relative to PAR-1. This study provides
      novel evidence that cardiomyocytes express functional PAR-4 whose signaling
      phenotype is distinct from PAR-1 in cardiomyocytes. AYPGKF, a modified PAR-4
      agonist with increased potency at PAR-4, activates p38-mitogen-activated protein
      kinase but is a weak activator of phospholipase C, extracellular signal-regulated
      kinase, and cardiomyocyte hypertrophy; AYPGKF and thrombin, but not the PAR-1
      agonist SFLLRN, activate Src. The observation that AYPGKF and thrombin activate
      Src in cardiomyocytes cultured from PAR-1(-/-) mice establishes that Src
      activation is via PAR-4 (and not PAR-1) in cardiomyocytes. Further studies
      implicate Src and epidermal growth factor receptor (EGFR) kinase activity in the
      PAR-4-dependent p38-mitogen-activated protein kinase signaling pathway. Thrombin
      phosphorylates EGFRs and ErbB2 via a PP1-sensitive pathway in PAR-1(-/-) cells
      that stably overexpress PAR-4; the Src-mediated pathway for EGFR/ErbB2
      transactivation underlies the protracted phases of thrombin-dependent
      extracellular signal-regulated kinase activation in PAR-1(-/-) cells that
      overexpress PAR-4 and in cardiomyocytes. These studies identify a unique
      signaling phenotype for PAR-4 (relative to other cardiomyocyte G protein-coupled
      receptors) that is predicted to contribute to cardiac remodeling and influence
      the functional outcome at sites of cardiac inflammation.

PMID- 12522107
TI  - Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of
      cyclooxygenase-2 and EGF receptor signaling.
AB  - We previously established that the trefoil peptides (TFFs) pS2, spasmolytic
      polypeptide, and intestinal trefoil factor are involved in cellular scattering
      and invasion in kidney and colonic cancer cells. Using the chorioallantoic
      membrane (CAM) assay and the formation of tube-like structures by human umbilical
      vein endothelial cells (HUVEC) plated on the Matrigel matrix substratum, we
      report here that TFFs are proangiogenic factors. Angiogenic activity of TFFs is
      comparable to that induced by vascular endothelial growth factor, leptin, and
      transforming growth factor-alpha. Stimulation of angiogenesis by pS2 in the CAM
      assay is blocked by pharmacological inhibitors of cyclooxygenase COX-2 (NS-398)
      and epidermal growth factor receptor (EGF-R) tyrosine kinase (ZD1839), but is
      independent of KDR/Flk-1 and thromboxane A2 receptors. In contrast, the
      morphogenic switch induced by pS2 in HUVEC cells could be inhibited by the
      specific KDR heptapeptide antagonist ATWLPPR and by inhibitors of COX-2 and EGF-R
      signaling. These results implicate TFFs in the formation of new blood vessels
      during normal and pathophysiological processes linked to wound healing,
      inflammation, and cancer progression in the digestive mucosa and other human
      solid tumors associated with aberrant expression of TFFs.

PMID- 12522108
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates endozepine
      release from cultured rat astrocytes via a PKA-dependent mechanism.
AB  - Astroglial cells synthesize and release endozepines, neuropeptides that are
      related to the octadecaneuropeptide ODN. Glial cells also express PACAP/VIP
      receptors. We have investigated the possible effect of PACAP on the release of
      ODN-like immunoreactivity (ODN-LI) by cultured rat astrocytes. Administration of
      PACAP27 and PACAP38 induced a concentration-dependent increase in secretion of
      ODN-LI whereas VIP was approximately 1000-fold less potent. The maximum effect of
      PACAP38 occurred after 5 min, then gradually declined during the next 10 min. The
      stimulatory effects of PACAP and VIP were abrogated by the PACAP antagonist
      PACAP6-38. PACAP38 stimulated cAMP formation, activated polyphosphoinositide
      turnover, and provoked calcium mobilization from IP3-sensitive pools. The PKA
      inhibitor H89 suppressed PACAP-induced secretion of ODN-LI, whereas PLC inhibitor
      U73122 and the PKC inhibitor chelerythrine had no effect. In contrast, U73122
      restored the stimulatory action of PACAP on ODN-LI release and cAMP formation
      during prolonged (15 min) incubation with the peptide, and this effect was
      prevented by PMA. The present results demonstrate that PACAP stimulates
      endozepine release through activation of PAC1 receptors coupled to the AC/PKA
      pathway. Our data also show that activation of the PLC/PKC pathway down-regulates
      the effect of PACAP on endozepine release.

PMID- 12522109
TI  - Agonist-induced mitochondrial Ca2+ transients in smooth muscle.
AB  - We investigated the role of mitochondria (MT) in calcium signaling in a culture
      of rat aortic smooth muscle cells. We used targeted aequorin to selectively
      measure [Ca2+] in this organelle. Our results reveal that smooth muscle cell
      stimulation with agonists causes a large, transient increase in mitochondrial
      [Ca2+] ([Ca2+]m). This large transient can be blocked with inhibitors of the
      sarco-endoplasmic reticulum Ca2+-ATPase, suggesting a close relationship between
      the sarcoplasmic reticulum (SR) and the mitochondria. FCCP completely abolished
      the response to agonists, and targeted mitochondrial GFP revealed a vast tubular
      network of MT in these cells. When added before stimulation with ATP, IP3
      inhibitors partially blocked the ATP-induced rise in mitochondrial Ca2+ release.
      The role of the Na+/Ca2+ exchanger (NCX) was examined by removing extracellular
      Na+. This procedure prevented the decrease in the [Ca2+]m transient normally seen
      on removal of extracellular Ca2+. We propose a functional linkage of MT and SR
      dependent on a narrow junctional space between the two organelles in which Ca2+
      diffusion is restricted. Approximately half of the mitochondria appear to be
      associated with the superficial SR, which communicates with the extracellular
      space via NCX.

PMID- 12522111
TI  - Editor's Foreword, 1953.

PMID- 12522112
TI  - Fifty years of cardiovascular science together.

PMID- 12522113
TI  - Stem cells to repair the heart: a clinical perspective.

PMID- 12522114
TI  - Angiotensin II: a vasoactive hormone with ever-increasing biological roles.

PMID- 12522115
TI  - Thrombosis of vein grafts: wall tension restrains thrombomodulin expression.

PMID- 12522116
TI  - A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in
      familial atrial standstill.
AB  - Atrial standstill (AS) is a rare arrhythmia that occasionally appears to be
      genetically determined. This study investigates the genetic background of this
      arrhythmogenic disorder in a large family. Forty-four family members were
      clinically evaluated. One deceased and three living relatives were unambiguously
      affected by AS. All other relatives appeared unaffected. Candidate gene screening
      revealed a novel mutation in the cardiac sodium channel gene SCN5A (D1275N) in
      all three affected living relatives and in five unaffected relatives, and the
      deceased relative was an obligate carrier. In addition, two closely linked
      polymorphisms were detected within regulatory regions of the gene for the atrial
      specific gap junction protein connexin40 (Cx40) at nucleotides -44 (G-->A) and
      +71 (A-->G). Eight relatives were homozygous for both polymorphisms, which
      occurred in only approximately 7% of control subjects, and three of these
      relatives were affected by AS. The three living AS patients exclusively
      coinherited both the rare Cx40 genotype and the SCN5A-D1275N mutation. SCN5A
      D1275N channels showed a small depolarizing shift in activation compared with
      wild-type channels. Rare Cx40 genotype reporter gene analysis showed a reduction
      in reporter gene expression compared with the more common Cx40 genotype. In this
      study, familial AS was associated with the concurrence of a cardiac sodium
      channel mutation and rare polymorphisms in the atrial-specific Cx40 gene. We
      propose that, although the functional effect of each genetic change is relatively
      benign, the combined effect of genetic changes eventually progresses to total AS.

PMID- 12522117
TI  - Stretch enhances contraction of bovine coronary arteries via an NAD(P)H oxidase
      mediated activation of the extracellular signal-regulated kinase mitogen
      activated protein kinase cascade.
AB  - This study examines the effects of an increase in passive stretch in endothelium
      removed bovine coronary artery on oxidant-induced changes in force generation.
      Increasing passive stretch on the arterial segments from 5 to 20 g for 20 minutes
      caused a subsequent increase (P<0.05) in force generation to 30 mmol/L KCl or 0.1
      micromol/L serotonin compared with the prestretch control response. Also
      associated with the passive stretch were increases in superoxide detection by
      lucigenin and a selective increase in extracellular signal-regulated kinase (ERK)
      mitogen-activated protein (MAP) kinase phosphorylation measured by Western
      analysis. The stretch-induced increase in force generation was eliminated by
      inhibition of the ERK pathway by the MEK inhibitor PD98059 but not by inhibitors
      of the p38 MAP kinase pathway (SB202190) or c-Jun N-terminal protein kinase
      pathway (SP200169). Additionally, stretch-induced increases in both ERK
      phosphorylation and force generation were attenuated by inhibition of tyrosine
      kinases (genistein), src (PP2), and specific sites on the epidermal growth factor
      receptor (EGFR) (AG1478). Probes for oxidant signaling, including NAD(P)H oxidase
      inhibitors (diphenyliodonium and apocynin) or enhancement of peroxide consumption
      (ebselen) but not inhibition of xanthine oxidase (allopurinol), attenuated the
      effects of stretch on both ERK phosphorylation and force generation. Furthermore,
      stretch caused an increase in EGFR phosphorylation and cytosolic to membrane
      translocation of the p47phox NAD(P)H oxidase subunit. Hydrogen peroxide also
      elicited contraction through EGFR phosphorylation and ERK. In summary, stretch
      seems to enhance force generation via ERK signaling through an EGFR/src-dependent
      mechanism activated by peroxide derived from a stretch-mediated activation of the
      NAD(P)H oxidase, a response that may contribute to hypertensive alterations in
      vascular reactivity.

PMID- 12522118
TI  - Relaxin, a pregnancy hormone, is a functional endothelin-1 antagonist:
      attenuation of endothelin-1-mediated vasoconstriction by stimulation of
      endothelin type-B receptor expression via ERK-1/2 and nuclear factor-kappaB.
AB  - We have recently demonstrated that relaxin (RLX) acts as compensatory mediator in
      human heart failure. RLX inhibits the stimulation of endothelin-1, the most
      potent vasoconstrictor in heart failure. Upregulation of the endothelin type-B
      receptor (ET(B)), which mediates endothelin-1 clearance and endothelial release
      of NO, represents a pivotal mode of RLX action. However, signal transduction and
      abundance of this phenomenon are unknown. Therefore, we investigated RLX-induced
      regulation of ET(B) in human umbilical vein endothelial, epithelial (HeLa), and
      vascular smooth muscle cells. In human umbilical vein endothelial cells and HeLa
      cells, but not in human vascular smooth muscle cells, RLX upregulated ET(B)
      expression and activated extracellular signal-regulated kinase-1/2 (ERK-1/2) and
      nuclear factor-kappaB (NF-kappaB), a transcription factor. PD-98059, a selective
      inhibitor of the mitogen-activated protein kinase kinase-1 (MEK-1)-ERK-1/2
      pathway, abolished ERK-1/2 and NF-kappaB activation and ET(B) upregulation. NF
      kappaB inhibition also prevented RLX-mediated ET(B) stimulation. In NF-kappaB
      luciferase reporter assays, we demonstrated complete inhibition of RLX-induced NF
      kappaB activation in cells transfected with dominant-negative Raf-1, MEK-1, or
      ERK-1/2 constructs, whereas dominant-negative Ras had no effect. In rat aorta and
      mesenteric artery, RLX pretreatment, in an ET(B)-dependent fashion, mitigated the
      maximum contractile response to endothelin-1, by 38+/-4% and 43+/-6%, and the
      endothelin-1 sensitivity (-log[EC(50)]: aorta, 8.2+/-0.2 for vehicle versus 7.2+/
      0.2 for RLX; mesenteric artery, 8.0+/-0.2 for vehicle versus 7.1+/-0.1 for RLX).
      RLX pretreatment augmented the dilator effect of the ET(B) agonist endothelin-3
      by 100+/-8% and 133+/-13%. In conclusion, RLX stimulates endothelial and
      epithelial ET(B) via a Ras-independent Raf-1-MEK-1-ERK-1/2 pathway that activates
      NF-kappaB. On vascular smooth muscle cells, ET(B), a contributor to endothelin
      mediated vasoconstriction, remains unaffected. This renders RLX a functional
      endothelin-1 antagonist.

PMID- 12522119
TI  - Wall tension is a potent negative regulator of in vivo thrombomodulin expression.
AB  - Thrombomodulin (TM), a key component of the anticoagulant protein C pathway, is a
      major contributor to vascular thromboresistance. We previously found that TM
      protein expression is dramatically reduced in autologous vein grafts during the
      first two weeks after implantation, coincident to a local inflammatory response,
      and remains suppressed for at least 6 weeks. To determine the proximate cause of
      TM loss, in vivo gene expression was quantified by real-time PCR. TM gene
      expression in vein grafts declined >85% during the first postoperative week and
      remained suppressed >55% at 6 weeks, accounting for the observed changes in
      protein expression. The effects of vein graft inflammation were evaluated in
      animals rendered leukopenic with vinblastine before graft implantation.
      Abrogating the local inflammatory response affected neither TM protein nor gene
      expression. To determine how hemodynamic forces might modulate TM expression, the
      surgical protocol was modified to alter blood flow and pressure-induced vessel
      distension. TM protein and gene expression did not correlate to changes in shear
      stress but highly correlated to changes in wall tension, both acutely and over
      time. We conclude that the primary stimulus for altered TM expression in vein
      grafts is the exposure to arterial pressure. Furthermore, these data identify
      strain as a novel and important pathway for in vivo TM gene regulation.

PMID- 12522120
TI  - Hibernating myocardium retains metabolic and contractile reserve despite regional
      reductions in flow, function, and oxygen consumption at rest.
AB  - Hibernating myocardium, characterized by reductions in flow and function at rest,
      has limited contractile reserve in response to increases in external workload. We
      hypothesized that this attenuation of function reflects an adaptive
      downregulation that prevents the development of metabolic evidence of ischemia
      during stress. To test this hypothesis, pigs were chronically instrumented with a
      proximal left anterior descending artery stenosis for 3 months, resulting in
      severe anteroapical hypokinesis with reduced resting perfusion (0.78+/-0.05
      versus 0.94+/-0.07 mL x min(-1)x g(-1) in remote, P<0.01; and 0.99+/-0.08 in
      controls, P<0.05). Open-chest studies confirmed resting dysfunction compared with
      normal controls (segment shortening 9.2+/-2.2% versus 23.5+/-1.1%, P<0.05).
      Resting myocardial oxygen consumption was reduced (63+/-3 versus 77+/-6 microL x
      g(-1) x min(-1) in controls, P<0.05), yet lactate consumption was normal.
      Although subendocardial perfusion failed to increase during graded, intravenous
      epinephrine infusion (n=8), peak segment shortening (to 17.3+/-3.1%, P<0.05) and
      oxygen consumption (to 90+/-6 microL x g(-1) x min(-1), P<0.01) increased from
      the depressed resting levels. There was no lactate production in hibernating
      myocardium, and lactate uptake increased during stress (0.7+/-0.1 to 1.2+/-0.1
      micromol x g(-1) x min(-1), P<0.05). The absence of metabolic evidence of
      ischemia was also confirmed during atrial pacing to a rate of 120 bpm (n=8).
      Thus, despite reductions in function and oxygen consumption at rest, hibernating
      myocardium retains the ability to increase metabolism without the development of
      acute ischemia. This supports the hypothesis that the downregulation of oxygen
      consumption and function in hibernating myocardium is an adaptive response that
      prevents a supply-demand imbalance during submaximal increases in cardiac
      workload when coronary flow reserve is limited.

PMID- 12522121
TI  - Oxidative stress-induced iron signaling is responsible for peroxide-dependent
      oxidation of dichlorodihydrofluorescein in endothelial cells: role of transferrin
      receptor-dependent iron uptake in apoptosis.
AB  - Dichlorodihydrofluorescein (DCFH) is one of the most frequently used probes for
      detecting intracellular oxidative stress. In this study, we report that H2O2
      dependent intracellular oxidation of DCFH to a green fluorescent product, 2',7'
      dichlorofluorescein (DCF), required the uptake of extracellular iron transported
      through a transferrin receptor (TfR) in endothelial cells. H2O2-induced DCF
      fluorescence was inhibited by the monoclonal IgA-class anti-TfR antibody (42/6)
      that blocked TfR endocytosis and the iron uptake. H2O2-mediated inactivation of
      cytosolic aconitase was responsible for activation of iron regulatory protein-1
      and increased expression of TfR, resulting in an increased iron uptake into
      endothelial cells. H2O2-mediated caspase-3 proteolytic activation was inhibited
      by anti-TfR antibody. Similar results were obtained in the presence of a lipid
      hydroperoxide. We conclude that hydroperoxide-induced DCFH oxidation and
      endothelial cell apoptosis required the uptake of extracellular iron by the TfR
      dependent iron transport mechanism and that the peroxide-induced iron signaling,
      in general, has broader implications in oxidative vascular biology.

PMID- 12522122
TI  - Rapid stimulation of L-arginine transport by D-glucose involves p42/44(mapk) and
      nitric oxide in human umbilical vein endothelium.
AB  - D-glucose infusion and gestational diabetes induce vasodilatation in humans and
      increase L-arginine transport and nitric oxide (NO) synthesis in human umbilical
      vein endothelial cells. High D-glucose (25 mmol/L, 2 minutes) induced membrane
      hyperpolarization and an increase of L-arginine transport (V(max) 6.1+/-0.7
      versus 4.4+/-0.1 pmol/ microg protein per minute) with no change in transport
      affinity (K(m) 105+/-9 versus 111+/-16 micromol/L). L-[3H]citrulline formation
      and intracellular cGMP, but not intracellular Ca2+, were increased by high D
      glucose. The effects of D-glucose were mimicked by levcromakalim (ATP-sensitive
      K+ channel blocker), paralleled by p42/p44(mapk) and Ser(1177)-endothelial NO
      synthase phosphorylation, inhibited by N(G)-nitro-L-arginine methyl ester (L
      NAME; NO synthesis inhibitor), glibenclamide (ATP-sensitive K+ channel blocker),
      KT-5823 (protein kinase G inhibitor), PD-98059 (mitogen-activated protein kinase
      kinase 1/2 inhibitor), and wortmannin (phosphatidylinositol 3-kinase inhibitor),
      but they were unaffected by calphostin C (protein kinase C inhibitor). Elevated D
      glucose did not alter superoxide dismutase activity. Our findings demonstrate
      that the human fetal endothelial L-arginine/NO signaling pathway is rapidly
      activated by elevated D-glucose via NO and p42/44(mapk). This could be
      determinant in pathologies in which rapid fluctuations of plasma D-glucose may
      occur and may underlie the reported vasodilatation in early stages of diabetes
      mellitus.

PMID- 12522123
TI  - The homeobox gene Lbx1 specifies a subpopulation of cardiac neural crest
      necessary for normal heart development.
AB  - Cardiac neural crest cells are known to play multiple roles during development of
      the inflow and outflow tract of the heart and the aortic arch. In addition,
      cardiac neural crest is required for normal heart tube looping and regulation of
      myocardial cell proliferation, as well as differentiation and function of the
      myocardium. We show that the homeobox gene Lbx1 is expressed in a subpopulation
      of the cardiac neural crest during tubular heart formation. Inactivation of the
      Lbx1 gene in mice resulted in defects in heart looping, changes in gene
      expression pattern, and increased cell proliferation ensuing in myocardial
      hyperplasia. We found that the activity of the Lbx1 promoter, as indicated by a
      LacZ reporter gene, is upregulated in the hearts of Lbx1(+/
      ):splotch(1H)/splotch(1H) and Lbx1(-/-) mice, indicating that Pax3 and Lbx1
      participate in a negative regulatory feedback that might be necessary for normal
      differentiation and function of the myocardium during early heart development.
      Because migration of Lbx1-expressing neural crest cells was not altered in Lbx1(
      /-) embryos, we postulate that Lbx1 gene function is critical for specification
      of a subpopulation of cardiac neural crest subsequent to migration.

PMID- 12522124
TI  - Glucocorticoid excess induces superoxide production in vascular endothelial cells
      and elicits vascular endothelial dysfunction.
AB  - Glucocorticoid (GC) excess often elicits serious adverse effects on the vascular
      system, such as hypertension and atherosclerosis, and effective prophylaxis for
      these complications is limited. We sought to reveal the mechanism underlying GC
      induced vascular complications. Responses in forearm blood flow to reactive
      hyperemia in 20 GC-treated patients were significantly decreased to 43+/-8.9%
      (mean+/-SEM) from the values obtained before GC therapy (130+/-14%). An
      administration of vitamin C almost normalized blood flow responses. In human
      umbilical vein endothelial cells (HUVECs), production of hydrogen peroxide was
      increased up to 166.5+/-3.3% of control values by 10(-7) mol/L dexamethasone
      (DEX) treatment (P<0.01). Concomitant with DEX-induced hydrogen peroxide
      production, intracellular amounts of peroxynitrite significantly increased and
      those of nitric oxide (NO) decreased, respectively (P<0.01). Immunoblotting
      analysis using anti-nitrotyrosine antibody showed that peroxynitrite formation
      was increased in DEX-treated HUVECs. Using inhibitors against metabolic pathways
      for generation of reactive oxygen species (ROS), we identified that the major
      production sources of ROS by DEX treatment were mitochondrial electron transport
      chain, NAD(P)H oxidase, and xanthine oxidase. These findings suggest that GC
      excess causes overproduction of ROS and thereby perturbs NO availability in the
      vascular endothelium, leading to vascular complications in patients with GC
      excess.

PMID- 12522125
TI  - Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and
      nitric oxide synthase activity.
AB  - In cultured endothelial cells, the antioxidant, L-ascorbic acid (vitamin C),
      increases nitric oxide synthase (NOS) enzyme activity via chemical stabilization
      of tetrahydrobiopterin. Our objective was to determine the effect of vitamin C on
      NOS function and tetrahydrobiopterin metabolism in vivo. Twenty-six to twenty
      eight weeks of diet supplementation with vitamin C (1%/kg chow) significantly
      increased circulating levels of vitamin C in wild-type (C57BL/6J) and
      apolipoprotein E (apoE)--deficient mice. Measurements of NOS enzymatic activity
      in aortas of apoE-deficient mice indicated a significant increase in total NOS
      activity. However, this increase was mainly due to high activity of inducible
      NOS, whereas eNOS activity was reduced. Significantly higher tetrahydrobiopterin
      levels were detected in aortas of apoE-deficient mice. Long-term treatment with
      vitamin C restored endothelial NOS activity in aortas of apoE-deficient mice, but
      did not affect activity of inducible NOS. In addition, 7,8-dihydrobiopterin
      levels, an oxidized form of tetrahydrobiopterin, were decreased and vascular
      endothelial function of aortas was significantly improved in apoE-deficient mice.
      Interestingly, vitamin C also increased tetrahydrobiopterin and NOS activity in
      aortas of C57BL/6J mice. In contrast, long-term treatment with vitamin E (2000
      U/kg chow) did not affect vascular NOS activity or metabolism of
      tetrahydrobiopterin. In vivo, beneficial effect of vitamin C on vascular
      endothelial function appears to be mediated in part by protection of
      tetrahydrobiopterin and restoration of eNOS enzymatic activity.

PMID- 12522126
TI  - Neuron-derived orphan receptor-1 (NOR-1) modulates vascular smooth muscle cell
      proliferation.
AB  - Vascular smooth muscle cells (VSMCs) migration and proliferation play a key role
      in the pathophysiology of cardiovascular disease. However, the transcription
      factors that regulate VSMC activation are not completely characterized. By a mRNA
      differential display approach, we have identified neuron-derived orphan receptor
      1 (NOR-1), a transcription factor within the NGFI-B subfamily of nuclear
      receptors, as a immediate-early gene in VSMCs. Two NOR-1 isoforms (alpha and
      beta) were identified and cloned from serum-induced porcine VSMC that shared high
      homology with the human isoforms. Northern blot analysis revealed a strong and
      transient (1 to 6 hours) upregulation of NOR-1 in both porcine and human coronary
      SMCs by growth factors (serum, platelet-derived growth factor-BB, and epidermal
      growth factor) and alpha-thrombin but not by cytokines. NOR-1 upregulation is
      processed through G protein-coupled receptors and tyrosine kinase receptors, and
      involves Ca2+ mobilization, protein kinase C activation, and the mitogen
      activated protein kinase pathway. This induction was closely dependent of the
      cAMP response elements present in NOR-1 promoter as transfection assays indicate.
      Human coronary atherosclerotic lesions overexpress NOR-1, and balloon angioplasty
      transiently induces NOR-1 in porcine coronary arteries with a pattern similar to
      that observed in VSMCs in culture. Antisense oligonucleotides against NOR-1
      inhibited human coronary SMC proliferation (reduced de novo DNA synthesis, cell
      cycle progression, and VSMC wound repair) as efficiently as antisense against the
      protooncogene c-fos. These results show that NOR-1 modulates VSMC proliferation,
      and suggest that this transcription factor may play a role in both spontaneous
      and accelerated atherosclerosis.

PMID- 12522127
TI  - Alpha-tocopherol induces expression of connective tissue growth factor and
      antagonizes tumor necrosis factor-alpha-mediated downregulation in human smooth
      muscle cells.
AB  - The effect of alpha-tocopherol treatment on gene expression in human aortic
      vascular smooth muscle cells was analyzed by gene expression arrays. The
      expression of the connective tissue growth factor (CTGF) gene was induced by
      alpha-tocopherol 1.8-fold in gene array experiments, and similar results were
      also obtained by RT-PCR (1.7-fold) and at the protein level (1.4-fold). The
      antioxidants beta-tocopherol and N-acetylcysteine did not induce CTGF gene
      expression, suggesting a nonantioxidant mechanism for alpha-tocopherol action.
      Protein kinase C (PKC) inhibition by alpha-tocopherol has been previously
      described. However, PKC downregulation did not prevent CTGF induction by alpha
      tocopherol, and inhibition of PKC activity with several inhibitors did not
      increase its expression, suggesting an alternative pathway for the alpha
      tocopherol effect. On the other hand, tumor necrosis factor-alpha reduced the
      expression of CTGF, an effect that was reversed by antioxidants. The data suggest
      that tumor necrosis factor-alpha inhibition of CTGF gene expression is prevented
      in an antioxidant-sensitive process and that alpha-tocopherol increases CTGF
      expression by a PKC-independent, nonantioxidant mechanism. Because CTGF
      stimulates the synthesis of extracellular matrix, the normalization of CTGF gene
      expression by alpha-tocopherol may accelerate wound repair and tissue
      regeneration during atherosclerosis.

PMID- 12522128
TI  - DNA microarray profiling to identify angiotensin-responsive genes in vascular
      smooth muscle cells: potential mediators of vascular disease.
AB  - Angiotensin II (Ang II) induces changes in vessel structure by its capacity to
      activate genes that are coupled to signaling pathways such as extracellular
      signal-regulated kinase (ERK), p38, and phosphatidylinositol 3-kinase (PI3K).
      Using a DNA microarray containing 5088 genes and expressed sequence tags, we
      initially established a database of replicated experiments (n=4) to define the
      variances in mRNA expression in response to Ang II versus vehicle treatment. We
      observed a wide range of values for the coefficients of variation in a gene
      specific manner. Guided by power calculations, we used statistical inference on a
      sufficient number of experimental replicates to minimize the number of false
      negatives and define a subset of Ang II-responsive genes (P<0.05). To further
      characterize the molecular circuitry that couples Ang II stimulation with mRNA
      expression, we assessed expression profiles in the presence and absence of
      inhibitors of ERK, p38, and PI3K. Using two different methods of computational
      cluster analysis, we identified a subset of six matricellular proteins (eg,
      osteopontin and plasminogen activator inhibitor-1) that are coordinately
      upregulated by Ang II via an ERK/p38-dependent pathway. In addition, these
      cluster analyses identified calpactins I and II as novel Ang II-responsive genes.
      Given that Ang II promotes vascular lesion formation, we examined whether this
      matricellular gene cluster was also coordinately regulated in vivo. Indeed, we
      demonstrate that both calpactin I and osteopontin are upregulated in response to
      vascular injury. Taken together, the combined use of DNA microarrays, statistical
      inference, and cluster analysis identified novel, coordinately regulated Ang II
      responsive genes that may mediate vascular lesion formation.

PMID- 12522129
TI  - Spatiotemporal characteristics of junctional and nonjunctional focal Ca2+ release
      in rat atrial myocytes.
AB  - Atrial myocytes have two functionally separate Ca2+ release sites: those in
      peripheral sarcoplasmic reticulum (SR) adjacent to the Ca2+ channels of surface
      membrane and those in central SR not associated with Ca2+ channels. Recently, we
      have reported on the gating of these two different Ca2+ release sites by Ca2+
      current. In the present study, we report on the spatiotemporal properties of
      focal Ca2+ releases (sparks) occurring spontaneously in central and peripheral
      sites of voltage-clamped rat atrial myocytes, using rapid 2-dimensional (2-D)
      confocal Ca2+ imaging. Peripheral and central sparks were similar in size and
      release time (approximately 300 000 Ca2+ ions for congruent with 12 ms), but
      significantly larger and longer than ventricular sparks. Both sites were
      resistant to Cd2+ and inhibited by ryanodine. Peripheral sparks were brighter and
      flattened against surface membrane, had approximately 5-fold higher frequency,
      approximately 2 times faster diffusion coefficient, and dissipated abruptly.
      Central sparks, in contrast, occurred less frequently, were elongated along the
      cellular longitudinal axis, and dissipated slowly. Compound sparks (composed of 2
      to 5 unitary focal releases) aligned longitudinally and occurred more frequently
      at the center. The diversity of peripheral and central sparks with respect to
      shape, frequency, and speed of spatial development and decay is consistent with
      regional ultrastructural heterogeneity of SR. The retarded dissipation of central
      atrial sparks, and high prevalence of compound sparks in cell center may be
      critical in facilitating the propagation of Ca2+ waves in atrial myocytes lacking
      t-tubular system and provide the atrial myocytes with functional Ca2+ signaling
      diversity. The full text of this article is available at
      http://www.circresaha.org.

PMID- 12522130
TI  - Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation.
AB  - Mammalian cardiomyocytes irreversibly lose their capacity to proliferate soon
      after birth, yet the underlying mechanisms have been unclear. Cyclin D1 and its
      partner, cyclin-dependent kinase 4 (CDK4), are important for promoting the G1-to
      S phase progression via phosphorylation of the retinoblastoma (Rb) protein.
      Mitogenic stimulation induces hypertrophic cell growth and upregulates expression
      of cyclin D1 in postmitotic cardiomyocytes. In the present study, we show that,
      in neonatal rat cardiomyocytes, D-type cyclins and CDK4 were predominantly
      cytoplasmic, whereas Rb remained in an underphosphorylated state. Ectopically
      expressed cyclin D1 localized in the nucleus of fetal but not neonatal
      cardiomyocytes. To target cyclin D1 to the nucleus efficiently, we constructed a
      variant of cyclin D1 (D1NLS), which directly linked to nuclear localization
      signals (NLSs). Coinfection of recombinant adenoviruses expressing D1NLS and CDK4
      induced Rb phosphorylation and CDK2 kinase activity. Furthermore, D1NLS/CDK4 was
      sufficient to promote the reentry into the cell cycle, leading to cell division.
      The number of cardiomyocytes coinfected with these viruses increased 3-fold 5
      days after infection. Finally, D1NLS/CDK4 promoted cell cycle reentry of
      cardiomyocytes in adult hearts injected with these viruses, evaluated by the
      expression of Ki-67, which is expressed in proliferating cells in all phases of
      the cell cycle, and BrdU incorporation. Thus, postmitotic cardiomyocytes have the
      potential to proliferate provided that cyclin D1/CDK4 accumulate in the nucleus,
      and the prevention of their nuclear import plays a critical role as a physical
      barrier to prevent cardiomyocyte proliferation. Our results provide new insights
      into the development of therapeutics strategies to induce regeneration of
      cardiomyocytes. The full text of this article is available at
      http://www.circresaha.org.

PMID- 12522131
TI  - Oxidized LDL promotes peroxide-mediated mitochondrial dysfunction and cell death
      in human macrophages: a caspase-3-independent pathway.
AB  - Several studies suggest that macrophage death and subsequent lysis contribute to
      the development of advanced atherosclerotic lesions. Although oxidized LDL
      (OxLDL) is thought to contribute to lesion formation and induces macrophage
      apoptosis, the mechanisms underlying macrophage lysis have not been well defined.
      To determine if induction of apoptosis in human macrophages also promotes cell
      lysis, we studied caspase-3 activation by OxLDL and activating anti-Fas
      antibodies. We found that Fas-induced activation of caspase-3 does not promote
      macrophage lysis and caspase-3 activation is not required for OxLDL-induced
      macrophage lysis. OxLDL induces the formation of peroxides, but not superoxide,
      and decreases mitochondrial membrane potential. Scavengers of peroxyl radicals
      restore mitochondrial membrane potential and prevent macrophage lysis,
      implicating peroxyl radicals in both mitochondrial dysfunction and macrophage
      lysis induced by OxLDL. We conclude that macrophage death induced by OxLDL
      results in cell lysis, but it does not require activation of Fas or caspase-3.
      The full text of this article is available at http://www.circresaha.org.

PMID- 12522132
TI  - Phosphorylation of tyrosine 319 of the angiotensin II type 1 receptor mediates
      angiotensin II-induced trans-activation of the epidermal growth factor receptor.
AB  - Although tyrosine kinases are critically involved in the angiotensin II (Ang II)
      type 1 (AT1) receptor signaling, how AT1 receptors activate tyrosine kinases is
      not fully understood. We examined the structural requirements of the AT1 receptor
      for transactivation of the epidermal growth factor (EGF) receptor (EGFR). Studies
      using carboxyl terminal-truncated AT1 receptors indicated that the amino acid
      sequence between 312 and 337 is required for activation of EGFR. The role of the
      conserved YIPP motif in this sequence in transactivation of EGFR was investigated
      by mutating tyrosine 319. Ang II failed to activate EGFR in cells expressing AT1
      Y319F, whereas EGFR was activated even without Ang II in cells expressing AT1
      Y319E, which mimics the AT1 receptor phosphorylated at Tyr-319. Immunoblot
      analyses using anti-phospho Tyr-319-specific antibody showed that Ang II
      increased phosphorylation of Tyr-319. EGFR interacted with the AT1 receptor but
      not with AT1-Y319F in response to Ang II stimulation, whereas the EGFR-AT1
      receptor interaction was inhibited in the presence of dominant negative SHP-2.
      The requirement of Tyr-319 seems specific for EGFR because Ang II-induced
      activation of other tyrosine kinases, including Src and JAK2, was preserved in
      cells expressing AT1-Y319F. Extracellular signal-regulated kinase activation was
      also maintained in AT1-Y319F through activation of Src. Overexpression of wild
      type AT1 receptor in cardiac fibroblasts enhanced Ang II-induced proliferation.
      By contrast, overexpression of AT1-Y319F failed to enhance cell proliferation. In
      summary, Tyr-319 of the AT1 receptor is phosphorylated in response to Ang II and
      plays a key role in mediating Ang II-induced transactivation of EGFR and cell
      proliferation, possibly through its interaction with SHP-2 and EGFR.

PMID- 12522133
TI  - p21-activated kinase 1 (PAK1) interacts with the Grb2 adapter protein to couple
      to growth factor signaling.
AB  - A variety of intracellular signaling pathways are linked to cell surface receptor
      signaling through their recruitment by Src homology 2 (SH2)/SH3-containing
      adapter molecules. p21-activated kinase 1 (PAK1) is an effector of Rac/Cdc42
      GTPases that has been implicated in the regulation of cytoskeletal dynamics,
      proliferation, and cell survival signaling. In this study, we describe the
      specific interaction of PAK1 with the Grb2 adapter protein both in vitro and in
      vivo. We identify the site of this interaction as the second proline-rich SH3
      binding domain of PAK1. Stimulation of the epidermal growth factor receptor
      (EGFR) in HaCaT cells enhances the level of EGFR-associated PAK1 and Grb2,
      although the PAK1-Grb2 association is itself independent of this stimulation. A
      cell-permeant TAT-tagged peptide encompassing the second proline-rich SH3 binding
      domain of PAK1 simultaneously blocked Grb2 and activated EGFR association with
      PAK1, in vitro and in vivo, indicating that Grb2 mediates the interaction of PAK1
      with the activated EGFR. Blockade of this interaction decreased the epidermal
      growth factor-induced extension of membrane lamellae. Thus Grb2 may serve as an
      important mechanism for linking downstream PAK signaling to various upstream
      pathways.

PMID- 12522134
TI  - Molecular identification of high and low affinity receptors for nicotinic acid.
AB  - Nicotinic acid has been used clinically for over 40 years in the treatment of
      dyslipidemia producing a desirable normalization of a range of cardiovascular
      risk factors, including a marked elevation of high density lipoprotein and a
      reduction in mortality. The precise mechanism of action of nicotinic acid is
      unknown, although it is believed that activation of a G(i)-G protein-coupled
      receptor may contribute. Utilizing available information on the tissue
      distribution of nicotinic acid receptors, we identified candidate orphan
      receptors. The selected orphan receptors were screened for responses to nicotinic
      acid, in an assay for activation of G(i)-G proteins. Here we describe the
      identification of the G protein-coupled receptor HM74 as a low affinity receptor
      for nicotinic acid. We then describe the subsequent identification of HM74A in
      follow-up bioinformatics searches and demonstrate that it acts as a high affinity
      receptor for nicotinic acid and other compounds with related pharmacology. The
      discovery of HM74A as a molecular target for nicotinic acid may facilitate the
      discovery of superior drug molecules to treat dyslipidemia.

PMID- 12522135
TI  - Anthrax lethal factor proteolysis and inactivation of MAPK kinase.
AB  - Anthrax lethal toxin produced by the bacterium Bacillus anthracis is the major
      cause of death in animals infected with anthrax. One component of this toxin,
      lethal factor (LF), inactivates members of the mitogen-activated protein kinase
      kinase or MEK family through proteolysis of their NH(2) termini. However, neither
      the substrate requirements for LF cleavage nor the mechanism by which proteolysis
      inactivates MEK have been demonstrated. By means of deletion mutant analysis and
      site-directed mutagenesis, we have identified an LFIR (LF interacting region) in
      the COOH-terminal kinase domain of MEK1 adjacent to the proline-rich region,
      which is essential for LF-mediated proteolysis of MEK. Point mutations in this
      region block proteolysis but do not alter the kinase activity of MEK. Similar
      mutations in MEK6 also prevent proteolysis, indicating that this region is
      functionally conserved among MEKs. In addition, NH(2)-terminal proteolysis of
      MEK1 by LF was found to reduce not only the affinity of MEK1 for its substrate
      mitogen-activated protein kinase but also its intrinsic kinase activity,
      indicating that the NH(2)-terminal end of MEK is important not only for substrate
      interaction but also for catalytic activity.

PMID- 12522136
TI  - Mammalian target of rapamycin and protein kinase A signaling mediate the cardiac
      transcriptional response to glutamine.
AB  - The addition of glutamine as a major nutrient to cultured neonatal rat
      cardiomyocytes produced an increase in myocyte size and the organization of actin
      into myofibrillar arrays. The cellular response was associated with increased
      abundance of the mRNAs encoding the contractile proteins, alpha-myosin heavy
      chain and cardiac alpha-actin, and the metabolic enzymes, muscle carnitine
      palmitoyl transferase I and muscle adenylosuccinate synthetase (ADSS1). Adss1
      gene expression was induced approximately 5-fold in glutamine-treated rat
      neonatal cardiac myocytes. The induction was mediated through the protein kinase
      A and mammalian target of rapamycin signaling pathways and required a cyclic AMP
      response element associated with the promoter region of the Adss1 gene. These
      results highlight glutamine as a major nutrient regulator of cardiac gene
      expression and identify protein kinase A and mammalian target of rapamycin
      signaling pathways as mediators of the cardiomyocyte transcriptional response.

PMID- 12522137
TI  - Suppression of hepatitis B virus core promoter by the nuclear orphan receptor
      TR4.
AB  - The TR4 orphan receptor is a member of the nuclear receptor superfamily that
      modulates gene expression via binding to the AGGTCA direct repeat hormone
      response element. Here we report a functional study of TR4 interaction with the
      core promoter of the hepatitis B virus (HBV). The electrophoretic mobility shift
      assay shows that TR4 can bind to the direct repeat 1 sequence element
      (AGGTTAAAGGTCT, nucleotide coordinates 1757-1769, TR4RE-HBV) on the HBV core
      promoter. TR4 also can enhance the activity of a synthetic luciferase reporter
      linked with four copies of TR4RE-HBV in either liver HepG2 or non-liver H1299
      cells in a dose-dependent manner. Surprisingly, TR4 represses the activity of a
      luciferase reporter containing the entire HBV genome sequences. Moreover,
      mutation of this TR4RE-HBV site in the HBV core promoter diminishes the TR4
      suppression effect. This TR4-induced suppression of HBV core promoter activity is
      further confirmed by primer extension analysis of the HBV core RNAs, showing that
      TR4 represses both pre-core and core mRNAs. Further dissection of this repressive
      mechanism indicates that TR4 may suppress the HBV core promoter activity via
      repressing HNF4alpha-mediated transactivation by protein-protein interactions
      without inhibition of HNF4alpha DNA binding. Furthermore, our results indicate
      that the N- and C-terminal regions of TR4 protein are required for TR4-HNF4alpha
      interaction. It is possible that TR4-HNF4alpha interaction may block the
      HNF4alpha function that results in the suppression of HBV gene expression.
      Together, these results demonstrate that TR4 can serve as a negative modulator in
      the transcriptional regulation of HBV core gene expression.

PMID- 12522138
TI  - Cytochrome oxidase assembly does not require catalytically active cytochrome C.
AB  - Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory
      chain, catalyzes the transfer of electrons from reduced cytochrome c to molecular
      oxygen. COX assembly requires the coming together of nuclear- and mitochondrial
      encoded subunits and the assistance of a large number of nuclear gene products
      acting at different stages of maturation of the enzyme. In Saccharomyces
      cerevisiae, expression of cytochrome c, encoded by CYC1 and CYC7, is required not
      only for electron transfer but also for COX assembly through a still unknown
      mechanism. We have attempted to distinguish between a functional and structural
      requirement of cytochrome c in COX assembly. A cyc1/cyc7 double null mutant
      strain was transformed with the cyc1-166 mutant gene (Schweingruber, M. E.,
      Stewart, J. W., and Sherman, F. (1979) J. Biol. Chem. 254, 4132-4143) that
      expresses stable but catalytically inactive iso-1-cytochrome c. The COX content
      of the cyc1/cyc7 double mutant strain harboring non-functional iso-1-cytochrome c
      has been characterized spectrally, functionally, and immunochemically. The
      results of these studies demonstrate that cytochrome c plays a structural rather
      than functional role in assembly of cytochrome c oxidase. In addition to its
      requirement for COX assembly, cytochrome c also affects turnover of the enzyme.
      Mutants containing wild type apocytochrome c in mitochondria lack COX, suggesting
      that only the folded and mature protein is able to promote COX assembly.

PMID- 12522139
TI  - PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1.
AB  - Presenilin (PS, PS1/PS2) complexes are known to be responsible for the
      intramembranous gamma-secretase cleavage of the beta-amyloid precursor protein
      and signaling receptor Notch. PS holoprotein undergoes endoproteolysis by an
      unknown enzymatic activity to generate NH(2)- and COOH-terminal fragments, a
      process that is required for the formation of the active and stable PS/-gamma
      secretase complex. Biochemical and genetic studies have recently identified
      nicastrin, APH-1, and PEN-2 as essential cofactors that physically interact with
      PS1 and are necessary for the gamma-secretase activity. However, their precise
      function in regulating the PS complex and gamma-secretase activity remains
      unknown. Here, we demonstrate that endogenous PEN-2 preferentially interacts with
      PS1 holoprotein. Down-regulation of PEN-2 expression by small interfering RNA
      (siRNA) abolishes the endoproteolysis of PS1, whereas overexpression of PEN-2
      promotes the production of PS1 fragments, indicating a critical role for PEN-2 in
      PS1 endoproteolysis. Interestingly, accumulation of full-length PS1 resulting
      from down-regulation of PEN-2 is alleviated by additional siRNA down-regulation
      of APH-1. Furthermore, overexpression of APH-1 facilitates PEN-2-mediated PS1
      proteolysis, resulting in a significant increase in PS1 fragments. Our data
      reveal a direct role of PEN-2 in proteolytic cleavage of PS1 and a regulatory
      function of APH-1, in coordination with PEN-2, in the biogenesis of the PS1
      complex.

PMID- 12522140
TI  - Dictyostelium differentiation-inducing factor-3 activates glycogen synthase
      kinase-3beta and degrades cyclin D1 in mammalian cells.
AB  - In search of chemical substances applicable for the treatment of cancer and other
      proliferative disorders, we studied the signal transduction of Dictyostelium
      differentiation-inducing factors (DIFs) in mammalian cells mainly using HeLa
      cells. Although DIF-1 and DIF-3 both strongly inhibited cell proliferation by
      inducing G(0)/G(1) arrest, DIF-3 was more effective than DIF-1. DIF-3 suppressed
      cyclin D1 expression at both mRNA and protein levels, whereas the overexpression
      of cyclin D1 overrode DIF-3-induced cell cycle arrest. The DIF-3-induced decrease
      in the amount of cyclin D1 protein preceded the reduction in the level of cyclin
      D1 mRNA. The decrease in cyclin D1 protein seemed to be caused by accelerated
      proteolysis, since it was abrogated by N-acetyl-Leu-Leu-norleucinal, a proteasome
      inhibitor. DIF-3-induced degradation of cyclin D1 was also prevented by treatment
      with lithium chloride, an inhibitor of glycogen synthase kinase-3beta (GSK
      3beta), suggesting that DIF-3 induced cyclin D1 proteolysis through the
      activation of GSK-3beta. Indeed, DIF-3 dephosphorylated Ser(9) and phosphorylated
      tyrosine on GSK-3beta, and it stimulated GSK-3beta activity in an in vitro kinase
      assay. Moreover, DIF-3 was revealed to induce the nuclear translocation of GSK
      3beta by immunofluorescent microscopy and immunoblotting of subcellular protein
      fractions. These results suggested that DIF-3 activates GSK-3beta to accelerate
      the proteolysis of cyclin D1 and that this mechanism is involved in the DIF-3
      induced G(0)/G(1) arrest in mammalian cells.

PMID- 12522141
TI  - Early changes in pancreatic acinar cell calcium signaling after pancreatic duct
      obstruction.
AB  - Intracellular Ca(2+)-changes not only participate in important signaling pathways
      but have also been implicated in a number of disease states including acute
      pancreatitis. To investigate the underlying mechanisms in an experimental model
      mimicking human gallstone-induced pancreatitis, we ligated the pancreatic duct of
      Sprague-Dawley rats and NMRI mice for up to 6 h and studied intrapancreatic
      changes including the dynamics of [Ca(2+)](i) in isolated acini. In contrast to
      bile duct ligation, pancreatic duct obstruction induced intra-pancreatic
      trypsinogen activation, leukocytosis, hyperamylasemia, and pancreatic edema and
      increased lung myeloperoxidase activity. Although resting [Ca(2+)](i) in isolated
      acini rose by 45% to 205 +/- 7 nmol, the acetylcholine- and cholecystokinin (CCK)
      stimulated calcium peaks as well as the amylase secretion declined, but neither
      the [Ca(2+)](i)-signaling pattern nor the amylase output in response to the
      Ca(2+)-ATPase inhibitor thapsigargin nor the secretin-stimulated amylase release
      were impaired by pancreatic duct ligation. On the single cell level pancreatic
      duct ligation reduced the percentage of cells in which submaximal secretagogue
      stimulation was followed by a physiological response (i.e. Ca(2+) oscillations)
      and increased the percentage of cells with a pathological response (i.e. peak
      plateau or absent Ca(2+) signal). Moreover, it reduced the frequency and
      amplitude of Ca(2+) oscillation as well as the capacitative Ca(2+) influx in
      response to secretagogue stimulation. Serum pancreatic enzyme elevation as well
      as trypsinogen activation was significantly reduced by pretreatment of animals
      with the calcium chelator BAPTA-AM. These experiments suggest that pancreatic
      duct obstruction rapidly changes the physiological response of the exocrine
      pancreas to a Ca(2+)-signaling pattern that has been associated with premature
      digestive enzyme activation and the onset of pancreatitis, both of which can be
      prevented by administration of an intracellular calcium chelator.

PMID- 12522142
TI  - Co-translational, intraribosomal cleavage of polypeptides by the foot-and-mouth
      disease virus 2A peptide.
AB  - During co-translational protein import into the endoplasmic reticulum ribosomes
      are docked onto the translocon. This prevents inappropriate exposure of nascent
      chains to the cytosol and, conversely, cytosolic factors from gaining access to
      the nascent chain. We exploited this property of co-translational translocation
      to examine the mechanism of polypeptide cleavage by the 2A peptide of the foot
      and-mouth disease virus. We find that the scission reaction is unaffected by
      placing 2A into a co-translationally targeted protein. Moreover, the portion of
      the polypeptide C-terminal to the cleavage site remains in the cytosol unless it
      contains its own signal sequence. The pattern of cleavage is consistent with the
      proposal that the 2A-mediated cleavage reaction occurs within the ribosome
      itself. In addition, our data indicate that the ribosome-translocon complex
      detects the break in the nascent chain and prevents any downstream protein
      lacking a signal sequence from gaining access to the endoplasmic reticulum.

PMID- 12522143
TI  - Low density lipoprotein receptor-related protein and factor IXa share structural
      requirements for binding to the A3 domain of coagulation factor VIII.
AB  - Low-density lipoprotein receptor-related protein (LRP) is an endocytic receptor
      that binds multiple distinct ligands, including blood coagulation factor VIII
      (FVIII). FVIII is a heterodimeric multidomain protein that consists of a heavy
      chain (domains A1, a1, A2, a2, and B) and a light chain (domains a3, A3, C1, and
      C2). Both chains contribute to high-affinity interaction with LRP. One LRP
      interactive region has previously been located in the C2 domain, but its affinity
      is low in comparison with that of the entire FVIII light chain. We now have
      compared a variety of FVIII light chain derivatives with the light chain of its
      homolog FVa for LRP binding. In surface plasmon resonance studies employing LRP
      cluster II, the FVa and FVIII light chains proved different in that only FVIII
      displayed high-affinity binding. Because the FVIII a3-A3-C1 fragment was
      effective in associating with LRP, this region was explored for structural
      elements that are exposed but not conserved in FV. Competition studies using
      synthetic peptides suggested that LRP binding involves the FVIII-specific region
      Lys(1804)-Ala(1834) in the A3 domain. In line with this observation, LRP binding
      was inhibited by a recombinant antibody fragment that specifically binds to the
      FVIII sequence Glu(1811)-Lys(1818). The role of this sequence in LRP binding was
      further tested using a FVIII/FV chimera in which sequence Glu(1811)-Lys(1818) was
      replaced with the corresponding sequence of FV. Although this chimera still
      displayed residual binding to LRP cluster II, its affinity was reduced. This
      suggests that multiple sites in FVIII contribute to high-affinity LRP binding,
      one of which is the FVIII A3 domain region Glu(1811)-Lys(1818). This suggests
      that LRP binding to the FVIII A3 domain involves the same structural elements
      that also contribute to the assembly of FVIII with FIXa.

PMID- 12522144
TI  - Membrane lipid organization is critical for human neutrophil polarization.
AB  - In response to chemoattractants neutrophils extend an actin-rich pseudopod, which
      imparts morphological polarity and is required for migration. Even when
      stimulated by an isotropic bath of chemoattractant, neutrophils exhibit
      persistent polarization and continued lamellipod formation at the front,
      suggesting that the cells establish an internal polarity. In this report, we show
      that perturbing lipid organization by depleting plasma membrane cholesterol
      levels reversibly inhibits cell polarization and migration. Among other receptor
      mediated responses, beta(2) integrin up-regulation was unaffected, and initial
      calcium mobilization was only partially reduced by cholesterol depletion,
      indicating that this treatment did not abrogate initial receptor-mediated signal
      transduction. Interestingly, cholesterol depletion did not prevent initial
      activation of the GTPase Rac or an initial burst of actin polymerization, but
      rather it inhibited prolonged activation of Rac and sustained actin
      polymerization. Collectively, these findings support a model in which the plasma
      membrane is organized into domains that aid in amplifying the chemoattractant
      gradient and maintaining cell polarization.

PMID- 12522145
TI  - Identification of targets for calcium signaling through the copine family of
      proteins. Characterization of a coiled-coil copine-binding motif.
AB  - We provide evidence that copines, members of a ubiquitous family of calcium
      dependent, membrane-binding proteins, may represent a universal transduction
      pathway for calcium signaling because we find copines are capable of interacting
      with a wide variety of "target" proteins including MEK1, protein phosphatase 5,
      and the CDC42-regulated kinase, that are themselves components of intracellular
      signaling pathways. The copine target proteins were identified by yeast two
      hybrid screening and the interactions were verified in vitro using purified
      proteins. In the majority of cases the copine binds to a domain of the target
      protein that is predicted to form a characteristic coiled-coil. A consensus
      sequence for the coiled-coil copine-binding site was derived and found to have
      predictive value for identifying new copine targets. We also show that
      interaction with copines may result in recruitment of target proteins to membrane
      surfaces and regulation of the enzymatic activities of target proteins.

PMID- 12522146
TI  - Single molecule characterization of P-selectin/ligand binding.
AB  - P-selectin expressed on activated platelets and vascular endothelium mediates
      adhesive interactions to polymorphonuclear leukocytes (PMNs) and colon carcinomas
      critical to the processes of inflammation and blood-borne metastasis,
      respectively. How the overall adhesiveness (i.e. the avidity) of receptor/ligand
      interactions is controlled by the affinity of the individual receptors to single
      ligands is not well understood. Using single molecule force spectroscopy, we
      probed in situ both the tensile strength and off-rate of single P-selectin
      molecules binding to single ligands on intact human PMNs and metastatic colon
      carcinomas and compared them to the overall avidity of these cells for P-selectin
      substrates. The use of intact cells rather than purified proteins ensures the
      proper orientation and preserves post-translational modifications of the P
      selectin ligands. The P-selectin/PSGL-1 interaction on PMNs was able to withstand
      forces up to 175 pN and had an unstressed off-rate of 0.20 s(-1). The tensile
      strength of P-selectin binding to a novel O-linked, sialylated protease-sensitive
      ligand on LS174T colon carcinomas approached 125 pN, whereas the unstressed off
      rate was 2.78 s(-1). Monte Carlo simulations of receptor/ligand bond rupture
      under constant loading rate for both P-selectin/PSGL-1 and P-selectin/LS174T
      ligand binding give distributions and mean rupture forces that are in accord with
      experimental data. The pronounced differences in the affinity for P
      selectin/ligand binding provide a mechanistic basis for the differential
      abilities of PMNs and carcinomas to roll on P-selectin substrates under blood
      flow conditions and underline the requirement for single molecule affinity
      measurements.

PMID- 12522147
TI  - Checkpoint arrest signaling in response to UV damage is independent of nucleotide
      excision repair in Saccharomyces cerevisiae.
AB  - The recognition of DNA double-stranded breaks or single-stranded DNA gaps as a
      precondition for cell cycle checkpoint arrest has been well established. However,
      how bulky base damage such as UV-induced pyrimidine dimers elicits a checkpoint
      response has remained elusive. Nucleotide excision repair represents the main
      pathway for UV dimer removal that results in strand interruptions. However, we
      demonstrate here that Rad53p hyperphosphorylation, an early event of checkpoint
      signaling in Saccharomyces cerevisiae, is independent of nucleotide excision
      repair (NER), even if replication as a source of secondary DNA damage is
      excluded. Thus, our data hint at primary base damage or at UV damage (primary or
      secondary) that does not need to be processed by NER as the relevant substrate of
      damage-sensing checkpoint proteins.

PMID- 12522148
TI  - 8-nitroguanosine formation in viral pneumonia and its implication for
      pathogenesis.
AB  - For many diseases, mediation of pathogenesis by nitric oxide (NO) has been
      suggested. In this study, we explored NO-induced viral pathogenesis with a focus
      on nucleic acid damage as evidenced by 8-nitroguanosine formation in vivo. Wild
      type mice and littermate mice deficient in inducible NO synthase (iNOS) were
      infected with influenza or Sendai virus. Formation of 8-nitroguanosine in virus
      infected lungs was assessed immunohistochemically with an antibody specific for 8
      nitroguanosine. Extensive nitration of RNA either treated with peroxynitrite or
      obtained from cultured RAW 264 cells expressing iNOS was readily detected by this
      antibody. Strong 8-nitroguanosine immunostaining was evident primarily in the
      cytosol of bronchial and bronchiolar epithelial cells of virus-infected wild-type
      mice but not iNOS-deficient mice. This staining colocalized with iNOS
      immunostaining in the lung. 8- Nitroguanosine staining disappeared after addition
      of exogenous authentic 8-nitroguanosine during the antibody reaction and after
      pretreatment of tissues with sodium hydrosulfite, which reduces 8-nitroguanosine
      to 8-aminoguanosine. NO was generated in excess in lungs of wild-type mice but
      was eliminated in iNOS-deficient mice after virus infection; this result also
      correlated well with formation of 8-nitroguanosine and 3-nitrotyrosine. One
      consequence of the lack of iNOS expression was marked improvement in
      histopathological changes in the lung and the lethality of the infection without
      effects on cytokine responses and viral clearance. It is intriguing that 8
      nitroguanosine markedly stimulated superoxide generation from cytochrome P450
      reductase and iNOS in vitro. The present data constitute a demonstration of 8
      nitroguanosine formation in vivo and suggest a potential role for NO-induced
      nitrative stress in viral pathogenesis.

PMID- 12522149
TI  - Impaired B cell development and function in mice with a targeted disruption of
      the homeobox gene Hex.
AB  - Hex is a homeobox gene that is expressed in all stages of B cell development
      except plasma cells. We studied lymphocyte development in the absence of Hex by
      using the RAG1-deficient blastocyst complementation system because homozygous
      disruption of Hex is embryonic lethal. Hex(-/-);RAG1(-/-) chimeric mice had
      severely reduced numbers of mature B cells, pre-B cells, and CD5(+) B cells with
      a striking 15-fold increase in the percentage of B220(-)CD19(+) cells in the bone
      marrow. Hex(-/-);RAG1(-/-) chimeric mice failed to generate IgG antibodies to T
      cell-independent antigens, although their serum IgM levels and antibody responses
      to T cell-dependent antigens were intact. Therefore, Hex is necessary for B cell
      development and function and its absence results in a dramatic increase in B220(
      )CD19(+) cells.

PMID- 12522150
TI  - Nondiffusive mechanisms enhance protein uptake rates in ion exchange particles.
AB  - Scanning confocal fluorescence microscopy and multiphoton fluorescence microscopy
      were used to image the uptake of the protein lysozyme into individual ion
      exchange chromatography particles in a packed bed in real time. Self-sharpening
      concentration fronts penetrating into the particles were observed at low salt
      concentrations in all of the adsorbents studied, but persisted to 100 mM ionic
      strength only in some materials. In other adsorbents, diffuse profiles were seen
      at these higher salt concentrations, with the transition region exhibiting a
      pronounced fluorescence peak at the front at intermediate salt concentrations.
      These patterns in the uptake profiles are accompanied by significant increases in
      protein uptake rates that are also seen macroscopically in batch uptake
      experiments. The fluorescence peak appears to be a concentration overshoot that
      may develop, in part, from an electrokinetic contribution to transport that also
      enhances the uptake rate. Further evidence for an electrokinetic origin is that
      the effect is correlated with high adsorbent surface charge densities.
      Predictions of a mathematical model incorporating the electrokinetic effect are
      in qualitative agreement with the observations. These findings indicate that
      mechanisms other than diffusion contribute to protein transport in oppositely
      charged porous materials and may be exploited to achieve rapid uptake in process
      chromatography.

PMID- 12522151
TI  - Expression and assembly of a fully active antibody in algae.
AB  - Although combinatorial antibody libraries have solved the problem of access to
      large immunological repertoires, efficient production of these complex molecules
      remains a problem. Here we demonstrate the efficient expression of a unique large
      single-chain (lsc) antibody in the chloroplast of the unicellular, green alga,
      Chlamydomonas reinhardtii. We achieved high levels of protein accumulation by
      synthesizing the lsc gene in chloroplast codon bias and by driving expression of
      the chimeric gene using either of two C. reinhardtii chloroplast promoters and 5'
      and 3' RNA elements. This lsc antibody, directed against glycoprotein D of the
      herpes simplex virus, is produced in a soluble form by the alga and assembles
      into higher order complexes in vivo. Aside from dimerization by disulfide bond
      formation, the antibody undergoes no detectable posttranslational modification.
      We further demonstrate that accumulation of the antibody can be modulated by the
      specific growth regime used to culture the alga, and by the choice of 5' and 3'
      elements used to drive expression of the antibody gene. These results demonstrate
      the utility of alga as an expression platform for recombinant proteins, and
      describe a new type of single chain antibody containing the entire heavy chain
      protein, including the Fc domain.

PMID- 12522152
TI  - WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to
      diverse Cl- -transporting epithelia.
AB  - Mutations in WNK1 and WNK4, genes encoding members of a novel family of serine
      threonine kinases, have recently been shown to cause pseudohypoaldosteronism type
      II (PHAII), an autosomal dominant disorder featuring hypertension, hyperkalemia,
      and renal tubular acidosis. The localization of these kinases in the distal
      nephron and the Cl(-) dependence of these phenotypes suggest that these mutations
      increase renal Cl(-) reabsorption. Although WNK4 expression is limited to the
      kidney, WNK1 is expressed in many tissues. We have examined the distribution of
      WNK1 in these extrarenal tissues. Immunostaining using WNK1-specific antibodies
      demonstrated that WNK1 is not present in all cell types; rather, it is
      predominantly localized in polarized epithelia, including those lining the lumen
      of the hepatic biliary ducts, pancreatic ducts, epididymis, sweat ducts, colonic
      crypts, and gallbladder. WNK1 is also found in the basal layers of epidermis and
      throughout the esophageal epithelium. The subcellular localization of WNK1 varies
      among these epithelia. WNK1 is cytoplasmic in kidney, colon, gallbladder, sweat
      duct, skin, and esophagus; in contrast, it localizes to the lateral membrane in
      bile ducts, pancreatic ducts, and epididymis. These epithelia are all notable for
      their prominent role in Cl(-) flux. Moreover, these sites largely coincide with
      those involved in the pathology of cystic fibrosis, a disease characterized by
      deranged epithelial Cl(-) flux. Together with the known pathophysiology of PHAII,
      these findings suggest that WNK1 plays a general role in the regulation of
      epithelial Cl(-) flux, a finding that suggests the potential of new approaches to
      the selective modulation of these processes.

PMID- 12522154
TI  - Responses of thalamic neurons to input from the male genitalia.
AB  - There have been relatively few electrophysiological studies, in any species,
      describing the supraspinal processing of inputs from the male genital tract. The
      thalamus was the focus of the present study. In 11 urethan-anesthetized male
      rats, subregions of the thalamus were surveyed for neuronal responses to the
      search stimulus, bilateral electrical stimulation of the dorsal nerve of the
      penis (DNP). A total of 133 DNP-responsive neurons were found and further tested
      for degree of somatovisceral convergence from other peripheral structures.
      Histological reconstruction of the recording sites revealed that the penile
      responsive neurons were distributed among various thalamic subregions. These
      thalamic subregions included the medial-dorsal nuclei and ventral and lateral
      thalamic subregions (majority of neurons responsive to both tactile and pinch
      stimulation of the penis) as well as intralaminar, posterior and reticular
      subregions (majority responsive to pinch only). Taken together, the data
      demonstrate the existence of thalamic neurons with inputs from the male genitalia
      with widespread somatovisceral convergence. These neurons likely contribute to
      the neural circuitries underlying various aspects of penile sensation associated
      with reproductive and nociceptive events.

PMID- 12522155
TI  - Neural control of rhythmic human arm movement: phase dependence and task
      modulation of hoffmann reflexes in forearm muscles.
AB  - Although we move our arms rhythmically during walking, running, and swimming, we
      know little about the neural control of such movements. Our working hypothesis is
      that neural mechanisms controlling rhythmic movements are similar in the human
      lumbar and cervical spinal cord. Thus reflex modulation during rhythmic arm
      movement should be similar to that seen during leg movement. Our main
      experimental hypotheses were that the amplitude of H-reflexes in the forearm
      muscles would be modulated during arm movement (i.e., phase-dependent) and would
      be inhibited during cycling compared with static contraction (i.e., task
      dependent). Furthermore, to determine the locus of any modulation, we tested the
      effect that active and passive movement of the ipsilateral (relative to
      stimulated arm) and contralateral arm had on H-reflex amplitude. Subjects
      performed rhythmic arm cycling on a custom-made hydraulic ergometer in which the
      two arms could be constrained to move together (180 degrees out of phase) or
      could rotate independently. Position of the stimulated limb in the movement cycle
      is described with respect to the clock face. H-reflexes were evoked at 12, 3, 6,
      and 9 o'clock positions during static contraction as well as during rhythmic arm
      movements. Reflex amplitudes were compared between tasks at equal M wave
      amplitudes and similar levels of electromyographic (EMG) activity in the target
      muscle. Surface EMG recordings were obtained bilaterally from flexor carpi
      radialis as well as from other muscles controlling the wrist, elbow, and
      shoulder. Compared with reflexes evoked during static contractions, movement of
      the stimulated limb attenuated H-reflexes by 50.8% (P < 0.005), 65.3% (P <
      0.001), and 52.6% (P < 0.001) for bilateral, active ipsilateral, and passive
      ipsilateral movements, respectively. In contrast, movement of the contralateral
      limb did not significantly alter H-reflex amplitude. H-reflexes were also
      modulated by limb position (P < 0.005). Thus task- and phase-dependent modulation
      were observed in the arm as previously demonstrated in the leg. The data support
      the hypothesis that neural mechanisms regulating reflex pathways in the moving
      limb are similar in the human upper and lower limbs. However, the inhibition of H
      reflex amplitude induced by contralateral leg movement is absent in the arms.
      This may reflect the greater extent to which the arms can be used independently.

PMID- 12522156
TI  - Activity-dependent release of adenosine contributes to short-term depression at
      CA3-CA1 synapses in rat hippocampus.
AB  - High-frequency stimulation results in a transient, presynaptically mediated
      decrease in synaptic efficacy called short-term depression (STD). Stimulation of
      Schaffer-collateral axons at 10 Hz for 5 s resulted in approximately 75%
      depression of excitatory postsynaptic current (EPSC) slope recorded from CA1
      cells in rat organotypic slice cultures. An adenosine A(1) receptor antagonist
      decreased the magnitude of STD elicited with 10-Hz stimulation by approximately
      30%. The A(1) receptor antagonist had no effect on STD elicited with 3-Hz
      stimulation. The activation of A(1) receptors during 10-Hz stimulation was not
      due to the extracellular conversion of released ATP to adenosine, because block
      of 5'-ectonucleotidases did not significantly affect STD. The adenosine transport
      inhibitor dipyridamole did not reduce STD, indicating that adenosine was not
      released by facilitated transport. We conclude that 10-Hz, but not 3-Hz,
      stimulation causes the vesicular release of adenosine and the rapid (<3 s)
      activation of presynaptic inhibitory A(1) receptors, which account for
      approximately 40% of homosynaptic EPSC depression.

PMID- 12522157
TI  - Influence of active dendritic currents on input-output processing in spinal
      motoneurons in vivo.
AB  - The extensive dendritic tree of the adult spinal motoneuron generates a powerful
      persistent inward current (PIC). We investigated how this dendritic PIC
      influenced conversion of synaptic input to rhythmic firing. A linearly
      increasing, predominantly excitatory synaptic input was generated in triceps
      ankle extensor motoneurons by slow stretch (duration: 2-10 s) of the Achilles
      tendon in the decerebrate cat preparation. The firing pattern evoked by stretch
      was measured by injecting a steady current to depolarize the cell to threshold
      for firing. The effective synaptic current (I(N), the net synaptic current
      reaching the soma of the cell) evoked by stretch was measured during voltage
      clamp. Hyperpolarized holding potentials were used to minimize the activation of
      the dendritic PIC and thus estimate stretch-evoked I(N) for a passive dendritic
      tree (I(N,PASS)). Depolarized holding potentials that approximated the average
      membrane potential during rhythmic firing allowed strong activation of the
      dendritic PIC and thus resulted in marked enhancement of the total stretch-evoked
      I(N) (I(N,TOT)). The net effect of the dendritic PIC on the generation of
      rhythmic firing was assessed by plotting stretch-evoked firing (strong PIC
      activation) versus stretch-evoked I(N,PASS) (minimal PIC activation). The gain of
      this input-output function for the neuron (I-O(N)) was found to be ~2.7 times as
      high as for the standard injected frequency current (F-I) function in low-input
      conductance neurons. However, about halfway through the stretch, firing rate
      tended to become constant, resulting in a sharp saturation in I-O(N) that was not
      present in F-I. In addition, the gain of I-O(N) decreased sharply with increasing
      input conductance, resulting in much lower stretch-evoked firing rates in high
      input conductance cells. All three of these phenomena (high initial gain,
      saturation, and differences in low- and high-input conductance cells) were also
      readily apparent in the differences between stretch-evoked I(N,TOT) and I(N,
      PASS) and thus could be accounted for by the activation of the dendritic PIC. As
      a result, stretch-evoked I(N,TOT) and F-I provided an accurate prediction of the
      overall change in stretch-evoked firing. However, in about half of the low-input
      conductance cells, the rate of rise of firing in response to stretch was not
      smoothly graded but instead consisted of a rapid surge. Stretch-evoked I(N,TOT)
      was always smoothly graded. This suggests that although stretch-evoked I(N,TOT)
      can be used to predict the overall change in firing, prediction of the dynamics
      of firing may be less accurate.

PMID- 12522158
TI  - Response properties of whisker-associated trigeminothalamic neurons in rat
      nucleus principalis.
AB  - Nucleus principalis (PrV) of the brain stem trigeminal complex mediates the
      processing and transfer of low-threshold mechanoreceptor input en route to the
      ventroposterior medial nucleus of the thalamus (VPM). In rats, this includes
      tactile information relayed from the large facial whiskers via primary afferent
      fibers originating in the trigeminal ganglion (NV). Here we describe the
      responses of antidromically identified VPM-projecting PrV neurons (n = 72) to
      controlled ramp-and-hold deflections of whiskers. For comparison, we also
      recorded the responses of 64 NV neurons under identical experimental and stimulus
      conditions. Both PrV and NV neurons responded transiently to stimulus onset (ON)
      and offset (OFF), and the majority of both populations also displayed sustained,
      or tonic, responses throughout the plateau phase of the stimulus (75% of NV cells
      and 93% of PrV cells). Average ON and OFF response magnitudes were similar
      between the two populations. In both NV and PrV, cells were highly sensitive to
      the direction of whisker deflection. Directional tuning was slightly but
      significantly greater in NV, suggesting that PrV neurons integrate inputs from NV
      cells differing in their preferred directions. Receptive fields of PrV neurons
      were typically dominated by a "principal" whisker (PW), whose evoked responses
      were on average threefold larger than those elicited by any given adjacent
      whisker (AW; n = 197). However, of the 65 PrV cells for which data from at least
      two AWs were obtained, most (89%) displayed statistically significant ON
      responses to deflections of one or more AWs. AW response latencies were 2.7 +/-
      3.8 (SD) ms longer than those of their corresponding PWs, with an inner quartile
      latency difference of 1-4 ms (+/-25% of median). The range in latency differences
      suggests that some adjacent whisker responses arise within PrV itself, whereas
      others have a longer, multi-synaptic origin, possibly via the spinal trigeminal
      nucleus. Overall, our findings reveal that the stimulus features encoded by
      primary afferent neurons are reflected in the responses of VPM-projecting PrV
      neurons, and that significant convergence of information from multiple whiskers
      occurs at the first synaptic station in the whisker-to-barrel pathway.

PMID- 12522159
TI  - Chronic NMDA receptor blockade from birth delays the maturation of NMDA currents,
      but does not affect AMPA/kainate currents.
AB  - The activity of the N-methyl-D-aspartate receptor (NR) regulates the composition
      of excitatory synapses and mediates multiple forms of synaptic and structural
      plasticity. In the superficial superior colliculus (sSC) of the rat, NR activity
      is essential for the full refinement of retinotopy during development. We have
      examined the NR's role in synaptic development by chronically treating the sSC
      from birth with the competitive antagonist (+/-)-2-amino-5-phosphonopentanoic
      acid (AP5) released by the slow-release polymer Elvax. Whole-cell voltage-clamp
      recordings were used to characterize excitatory postsynaptic potentials (EPSCs)
      in slices from postnatal day (P)12-20 sSC. Chronic NR blockade reduced the ratio
      of AMPA/kainate receptor (AMPAR) to NR peak current amplitudes of both
      spontaneous (s)EPSCs and evoked EPSCs. Spontaneous NR current amplitude was
      increased following treatment, while spontaneous AMPAR currents were identical to
      those of controls, indicating that the ratio change was due to an increased NR
      current. Comparison of sEPSC frequency, AMPAR current rectification, and
      quantitative Western blots indicated that the characteristics of AMPARs at the
      synapse are normal following AP5 treatment. In the sSC, NR currents show a rapid
      decrease in decay time on P11 and previous studies in slices indicate this change
      results from a NR-mediated activation of the phosphatase calcineurin. Consistent
      with this in vitro finding, the down-regulation failed to occur in sSC
      chronically treated with AP5 in vivo. Together the present data show that NR
      function is necessary for subsequent NR current regulation in vivo, but it is not
      essential for the developmental expression of normal AMPAR currents.

PMID- 12522160
TI  - Evidence for functionally distinct synaptic NMDA receptors in ventromedial versus
      dorsolateral striatum.
AB  - N-methyl-D-aspartate receptors (NMDARs) are comprised of different subunits. NR2
      subunits confer different pharmacological and biophysical properties to NMDARs.
      Although NR2B subunit expression is uniform throughout striatum, NR2A subunit
      expression is greater laterally. Pharmacologically isolated NMDAR-mediated
      excitatory postsynaptic currents (NMDAR-EPSCs) were elicited using minimal local
      stimulation and recorded in the whole cell configuration to test the hypothesis
      that biophysical and pharmacological properties of NMDAR-EPSCs of striatal
      neurons would vary as a function of their location in adult rat striatum. We
      observed that the decay-time kinetics of NMDAR-EPSCs are significantly slower in
      neurons of ventromedial versus dorsolateral striatum. Whereas ifenprodil did not
      differentially affect NMDAR-EPSCs in these regions, application of either glycine
      or D-serine increased the peak current of NMDAR-EPSCs selectively in dorsolateral
      striatum. These data provide evidence for functionally distinct NMDARs in the
      same neuron type in the same brain region of the adult rodent brain. These data
      thus suggest that the nature of synaptic processing of excitatory input is
      different in the ventromedial and dorsolateral striatum of the adult rodent
      brain, regions differentially involved in limbic versus sensorimotor processes,
      respectively.

PMID- 12522161
TI  - Endogenous waves in hippocampal slices.
AB  - Sharp waves (SPWs) are thought to play a major role in intrinsic hippocampal
      operations during states in which subcortical and cortical inputs to hippocampus
      are reduced. This study describes evidence that such activity occurs
      spontaneously in appropriately prepared rat hippocampal slices. Irregular waves,
      with an average frequency of approximately 4 Hz, were recorded from field CA3 in
      slices prepared from the temporal region of hippocampus. The waves persisted for
      hours and were not accompanied by aberrant discharges. Multi-electrode analyses
      established that they were locally generated within each of the subfields of CA3
      and yet were coherent between subfields. The sharp waves were reversibly blocked
      by either cholinergic or serotonergic stimulation. Various lines of evidence
      indicate that they are propagated by the CA3 associational system.

PMID- 12522162
TI  - Augmentation of plasticity of the central auditory system by the basal forebrain
      and/or somatosensory cortex.
AB  - Auditory conditioning (associative learning) or focal electric stimulation of the
      primary auditory cortex (AC) evokes reorganization (plasticity) of the
      cochleotopic (frequency) map of the inferior colliculus (IC) as well as that of
      the AC. The reorganization results from shifts in the best frequencies (BFs) and
      frequency-tuning curves of single neurons. Since the importance of the
      cholinergic basal forebrain for cortical plasticity and the importance of the
      somatosensory cortex and the corticofugal auditory system for collicular and
      cortical plasticity have been demonstrated, Gao and Suga proposed a hypothesis
      that states that the AC and corticofugal system play an important role in evoking
      auditory collicular and cortical plasticity and that auditory and somatosensory
      signals from the cerebral cortex to the basal forebrain play an important role in
      augmenting collicular and cortical plasticity. To test their hypothesis, we
      studied whether the amount and the duration of plasticity of both collicular and
      cortical neurons evoked by electric stimulation of the AC or by acoustic
      stimulation were increased by electric stimulation of the basal forebrain and/or
      the somatosensory cortex. In adult big brown bats (Eptesicus fuscus), we made the
      following major findings. 1) Collicular and cortical plasticity evoked by
      electric stimulation of the AC is augmented by electric stimulation of the basal
      forebrain. The amount of augmentation is larger for cortical plasticity than for
      collicular plasticity. 2) Collicular and cortical plasticity evoked by AC
      stimulation is augmented by somatosensory cortical stimulation mimicking fear
      conditioning. The amount of augmentation is larger for cortical plasticity than
      for collicular plasticity. 3) Collicular and cortical plasticity evoked by both
      AC and basal forebrain stimulations is further augmented by somatosensory
      cortical stimulation. 4) A lesion of the basal forebrain tends to reduce
      collicular and cortical plasticity evoked by AC stimulation. The reduction is
      small and statistically insignificant for collicular plasticity but significant
      for cortical plasticity. 5) The lesion of the basal forebrain eliminates the
      augmentation of collicular and cortical plasticity that otherwise would be evoked
      by somatosensory cortical stimulation. 6) Collicular and cortical plasticity
      evoked by repetitive acoustic stimuli is augmented by basal forebrain and/or
      somatosensory cortical stimulation. However, the lesion of the basal forebrain
      eliminates the augmentation of collicular and cortical plasticity that otherwise
      would be evoked by somatosensory cortical stimulation. These findings support the
      hypothesis proposed by Gao and Suga.

PMID- 12522163
TI  - Rhythmic whisking by rat: retraction as well as protraction of the vibrissae is
      under active muscular control.
AB  - The rhythmic motor activity of the vibrissae that rodents use for the tactile
      localization of objects provides a model system for understanding patterned motor
      activity in mammals. The muscles that drive this whisking are only partially
      fixed relative to bony attachments and thus shift their position along with the
      movement. As a means to characterize the pattern of muscular dynamics during
      different patterns of whisking, we recorded electromyogram (EMG) activity from
      the muscles that propel individual follicles, as well as EMG activity from a
      muscle group that moves the mystacial pad. The dominant pattern of whisking in
      our behavioral paradigm, referred to as exploratory whisking, consisted of large
      amplitude sweeps in the frequency range of 5-15 Hz. The frequency remained
      remarkably constant within a bout of whisking but changed values between bouts.
      The extrinsic musculature, which shifts the surface of the pad backwards, was
      found to be activated in approximate antiphase to that of the intrinsic muscles,
      which rotate individual vibrissae forward. Thus retraction of the vibrissae was
      driven by a backward shift in the attachment point of the follicles to the
      mystacial pad. In a less frequent pattern of whisking, referred to as foveal
      whisking, the vibrissae are thrust forward and palpate objects with low-amplitude
      movements that are in the higher frequency range of 15-25 Hz. Protraction of the
      vibrissae remains driven by the intrinsic muscles, while retraction in this
      pattern is largely passive. Interestingly, a mechanical argument suggests that
      activation of the extrinsic muscles during foveal whisking is not expected to
      affect the angle of the vibrissae. As a means to establish if the phasic control
      of the intrinsic versus extrinsic muscles depended on sensory feedback, we
      characterized whisking before and after bilateral transections of the
      infraorbital branch of the trigeminal sensory nerve. The loss of sensory feedback
      had no net effect on the antiphase relation between activation of the intrinsic
      versus extrinsic muscles over the full frequency range for exploratory whisking.
      These data point to the existence of a dual-phase central pattern generator that
      drives the vibrissae.

PMID- 12522164
TI  - Ion conductances in supporting cells isolated from the mouse vomeronasal organ.
AB  - The vomeronasal organ (VNO) is a chemosensory structure involved in the detection
      of pheromones in most mammals. The VNO sensory epithelium contains both neurons
      and supporting cells. Data suggest that vomeronasal neurons represent the
      pheromonal transduction sites, whereas scarce information is available on the
      functional properties of supporting cells. To begin to understand their role in
      VNO physiology, we have characterized with patch-clamp recording techniques the
      electrophysiological properties of supporting cells isolated from the
      neuroepithelium of the mouse VNO. Supporting cells were distinguished from
      neurons by their typical morphology and by the lack of immunoreactivity for
      Ggamma8 and OMP, two specific markers for vomeronasal neurons. Unlike glial cells
      in other tissues, VNO supporting cells exhibited a depolarized resting potential
      (about -29 mV). A Goldman-Hodgkin-Katz analysis for resting ion permeabilities
      revealed indeed an unique ratio of P(K):P(Na):P(Cl) = 1:0.23:1.4. Supporting
      cells also possessed voltage-dependent K(+) and Na(+) conductances that differed
      significantly in their biophysical and pharmacological properties from those
      expressed by VNO neurons. Thus glial membranes in the VNO can sustain significant
      fluxes of K(+) and Na(+), as well as Cl(-). This functional property might allow
      supporting cells to mop-up and redistribute the excess of KCl and NaCl that often
      occurs in certain pheromone-delivering fluids, like urine, and that could blunt
      the sensitivity of VNO neurons to pheromones. Therefore vomeronasal supporting
      cells could affect chemosensory transduction in the VNO by regulating the ionic
      strength of the pheromone-containing medium.

PMID- 12522165
TI  - GABA(A) receptor beta3 subunit deletion decreases alpha2/3 subunits and IPSC
      duration.
AB  - Deletion of the beta3 subunit of the GABA(A) receptor produces severe behavioral
      deficits and epilepsy. GABA(A) receptor-mediated miniature inhibitory
      postsynaptic currents (mIPSCs) in cortical neurons in cultures from beta3 -/-
      mice were significantly faster than those in beta3 +/+ mice and were more
      prolonged by zolpidem. Surface staining revealed that the number of beta2/3,
      alpha2, and alpha3 (but not of alpha1) subunit-expressing neurons and the
      intensity of subunit clusters were significantly reduced in beta3 -/- mice.
      Transfection of beta3 -/- neurons with beta3 cDNA restored beta2/3, alpha2, and
      alpha3 subunits immunostaining and slowed mIPSCs decay. We show that the deletion
      of the beta3 subunit causes the loss of a subset of GABA(A) receptors with alpha2
      and alpha3 subunits while leaving a receptor population containing predominantly
      alpha1 subunit with fast spontaneous IPSC decay and increased zolpidem
      sensitivity.

PMID- 12522166
TI  - Blockade of brain stem gap junctions increases phrenic burst frequency and
      reduces phrenic burst synchronization in adult rat.
AB  - Recent investigations have examined the influence of gap junctional communication
      on generation and modulation of respiratory rhythm and inspiratory motoneuron
      synchronization in vitro using transverse medullary slice and en bloc brain stem
      spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap
      junction proteins, however, have been identified in both neurons and glia in
      brain stem regions implicated in respiratory control in both neonatal and adult
      rodents. Here, we used an in vitro arterially perfused rat preparation to examine
      the role of gap junctional communication on generation and modulation of
      respiratory rhythm and inspiratory motoneuron synchronization in adult rodents.
      We recorded rhythmic inspiratory motor activity from one or both phrenic nerves
      before and during pharmacological blockade (i.e., uncoupling) of brain stem gap
      junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100
      microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or
      heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we
      observed an increase in the frequency of phrenic bursts (~95% above baseline
      frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic
      nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted
      from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the
      pattern of phrenic nerve discharge shifted from an augmenting discharge pattern
      to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral
      analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in
      the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90-
      to 110-Hz peak (corresponding to the HFO) although spurious higher frequency
      activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in
      inspiratory-phase synchronization. Although additional experiments are required
      to identify the specific brain stem regions and cell types (i.e., neurons, glia)
      mediating the observed modulations in phrenic motor output, these findings
      suggest that gap junction communication modulates generation of respiratory
      rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.

PMID- 12522167
TI  - Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic
      gray matter.
AB  - Neuronal heterotopia has a strong association with epilepsy, but the mechanisms
      that underlie this relationship are largely unknown. We have utilized the in
      utero irradiated rat model to study circuit abnormalities in experimentally
      induced subcortical heterotopic gray matter. Spontaneous and miniature inhibitory
      (IPSCs) and excitatory (EPSCs) postsynaptic currents were recorded from
      visualized heterotopic pyramidal neurons in in vitro hemispheric slices and
      compared with control neocortical pyramidal neurons using the whole cell patch
      clamp technique. The frequency of spontaneous and miniature IPSCs was
      significantly reduced in pyramidal neurons from heterotopic cortex. Amplitude and
      kinetics of IPSCs were not different between the two groups. Spontaneous and
      miniature EPSCs were not different between the two groups. Short-term synaptic
      plasticity of stimulus-evoked EPSCs showed depression in heterotopic neurons and
      facilitation in control pyramidal neurons. This study shows a selective
      impairment of the GABAergic circuitry in experimental heterotopic gray matter. We
      have reported similar findings in normotopic dysplastic cortex from this model.
      Taken together, these studies demonstrate a pervasive defect in inhibition
      throughout the cortex of irradiated rats with cortical dysplasia and neuronal
      heterotopia. This may have important implications regarding cortical development
      and function following in utero injuries.

PMID- 12522168
TI  - Cross talk between the GABA(A) receptor and the Na-K-Cl cotransporter is mediated
      by intracellular Cl-.
AB  - It has been suggested that the GABA(A) receptor-mediated depolarization in
      immature neurons depends on a high intracellular Cl(-) concentration maintained
      by Na-K-Cl cotransporter isoform1 (NKCC1). We previously found that activation of
      the GABA(A) receptor led to stimulation of NKCC1. This stimulation could be a
      result of GABA(A) receptor-mediated Cl(-) efflux. However, a loss of
      intracellular Cl(-) is associated with cell shrinkage, membrane depolarization,
      as well as a rise of intracellular Ca(2+) concentration ([Ca(2+)](i)). To
      determine which cellular mechanism is underlying NKCC1 stimulation, we
      investigated changes of intracellular Cl(-) content, [Ca(2+)](i), cell volume,
      and NKCC1 activity following GABA(A) receptor activation. The basal levels of
      intracellular (36)Cl were 0.70 +/- 0.04 micromol/mg protein. The intracellular
      (36)Cl content decreased to 0.53 +/- 0.03 micromol/mg protein in response to 30
      microM muscimol (P < 0.05). The loss of intracellular (36)Cl was blocked by 10
      microM bicuculline. Muscimol triggered a rise in [Ca(2+)](i), but did not cause
      cell shrinkage. In contrast, 10-50 mM [Cl(-)](o) or hypertonic HEPES-MEM resulted
      in reversible cell shrinkage (P < 0.05). Moreover, the GABA-mediated stimulation
      of NKCC1 activity was not abolished either by removal of extracellular Ca(2+) or
      BAPTA-AM. An increase in phosphorylation of NKCC1 was detected under both 10 mM
      [Cl(-)](o) and muscimol conditions. These results suggest that a GABA-mediated
      loss of intracellular Cl(-), but not a subsequent rise in [Ca(2+)](i) or
      shrinkage, leads to stimulation of NKCC1. This stimulation may be an important
      positive feedback mechanism to maintain intracellular Cl(-) level and GABA
      function in immature neurons.

PMID- 12522169
TI  - Learned dynamics of reaching movements generalize from dominant to nondominant
      arm.
AB  - Accurate performance of reaching movements depends on adaptable neural circuitry
      that learns to predict forces and compensate for limb dynamics. In earlier
      experiments, we quantified generalization from training at one arm position to
      another position. The generalization patterns suggested that neural elements
      learning to predict forces coded a limb's state in an intrinsic, muscle-like
      coordinate system. Here, we test the sensitivity of these elements to the other
      arm by quantifying inter-arm generalization. We considered two possible
      coordinate systems: an intrinsic (joint) representation should generalize with
      mirror symmetry reflecting the joint's symmetry and an extrinsic representation
      should preserve the task's structure in extrinsic coordinates. Both coordinate
      systems of generalization were compared with a naive control group. We tested
      transfer in right-handed subjects both from dominant to nondominant arm (D-->ND)
      and vice versa (ND-->D). This led to a 2 x 3 experimental design matrix: transfer
      direction (D-->ND/ND-->D) by coordinate system (extrinsic, intrinsic, control).
      Generalization occurred only from dominant to nondominant arm and only in
      extrinsic coordinates. To assess the dependence of generalization on callosal
      inter-hemispheric communication, we tested commissurotomy patient JW. JW showed
      generalization from dominant to nondominant arm in extrinsic coordinates. The
      results suggest that when the dominant right arm is used in learning dynamics,
      the information could be represented in the left hemisphere with neural elements
      tuned to both the right arm and the left arm. In contrast, learning with the
      nondominant arm seems to rely on the elements in the nondominant hemisphere tuned
      only to movements of that arm.

PMID- 12522170
TI  - Actions of U-92032, a T-type Ca2+ channel antagonist, support a functional
      linkage between I(T) and slow intrathalamic rhythms.
AB  - Thalamic relay neurons express high levels of T-type Ca(2+) channels, which
      support the generation of robust burst discharges. This intrinsically mediated
      form of phasic spike firing is thought to be critical in the generation of slow
      (3-4 Hz) synchronous oscillatory activity of absence epilepsy. Recordings made
      from brain slices or whole animals have shown that slow synchronous absence-like
      activity can be abolished when Ca(2+)-dependent burst firing in relay neurons is
      interrupted by the pharmacological or genetic inactivation of T-channels. Because
      succinimide drugs act as incomplete and nonspecific antagonists, we tested
      whether the novel T-channel antagonist U-92032 could provide stronger support for
      a role of T-channels in slow oscillatory activity. Ca(2+)-dependent rebound (LTS)
      bursts were recorded using whole cell current clamp in relay cells of the ventral
      basal complex (VB) from thalamic slices of adult rats. We used LTS kinetics to
      measure the availability of T-channels in VB cells after TTX. U-92032 (1 and 10
      microM) reduced the maximum rate of depolarization of the isolated LTS by 51% and
      90%, respectively, compared with the 35% reduction due to 2 mM
      methylphenylsuccinimide (MPS), the active metabolite of the antiabsence drug
      methsuximide. U-92032 (1 and 10 microM) also suppressed evoked, slow oscillations
      in thalamic slices with a time course similar for observed intracellular effects.
      Unlike MPS, we observed no substantial effects of short-term U-92032 applications
      (< or =2 h) on the generation of action potentials in VB cells. Our findings show
      U-92032 is a more potent, effective, and specific T-channel antagonist than
      previously studied succinimide antiabsence drugs and that it dramatically reduces
      epileptiform synchronous activity. This suggests that U-92032 or other specific T
      channel antagonists may provide effective drug treatments for absence epilepsy.

PMID- 12522172
TI  - Frequency-dependent properties of inhibitory synapses in the rostral nucleus of
      the solitary tract.
AB  - To explore the parameters that define the characteristics of either inhibitory
      postsynaptic potentials (IPSP) or currents (IPSC) in the gustatory nucleus of the
      solitary tract (rNST), whole cell patch-clamp recordings were made in horizontal
      brain stem slices of newborn rats. Neurons were labeled with biocytin to confirm
      both their location and morphology. IPSPs or IPSCs were evoked by delivering
      either single, paired-pulse, or tetanic stimulus shocks (0.1-ms duration) via a
      bipolar stimulating electrode placed on the rNST. Pure IPSP/IPSCs were isolated
      by the use of glutamate receptor antagonists. For 83% of the single-stimulus
      evoked IPSCs, the decay time course was fitted with two exponentials having
      average time constants of 38 and 181 ms, respectively, while the remainder could
      be fitted with one exponential of 59 ms. Paired-pulse stimulation resulted in
      summation of the amplitude of the conditioning and test-stimulus-evoked IPSCs.
      The decay time course of the test-stimulus-evoked IPSC was slower when compared
      to the decay time of the conditioning stimulus IPSC. Repeated stimulation
      resulted in an increase in the decay time of the IPSP/Cs where each consecutive
      stimulus contributed to prolongation of the decay time constant. Most of the
      IPSP/Cs resulting from a 1-s >/= 30-Hz tetanic stimulus exhibited an S-shaped
      decay time course where the amplitude of the IPSP/Cs after termination of the
      stimulus was initially sustained before starting to decay back to the resting
      membrane potential. Elevation of extracellular Ca(2+) concentration 10 mM
      resulted in an increase in the amplitude and decay time of single-stimulus shock
      evoked IPSP/Cs. The benzodiazepine GABA(A) receptor modulator diazepam increased
      the decay time of single-stimulus shock-evoked IPSCs. However, application of
      diazepam did not affect the decay time of tetanic-stimulation-evoked IPSP/Cs.
      These results suggest that the decay time of single-stimulus-evoked IPSCs is
      defined either by receptor kinetics or neurotransmitter clearance from the
      synaptic cleft or both, while the decay time course of the tetanic stimulus
      evoked IPSP/Cs is defined by neurotransmitter diffusion from the synaptic cleft.
      During repetitive stimulation, neurotransmitter accumulates in the synaptic cleft
      prolonging the decay time constant of the IPSCs. High-frequency stimulation
      elevates the GABA concentration in the synaptic cleft, which then oversaturates
      the postsynaptic receptors, and, as a consequence, after termination of the
      tetanic stimulus, the amplitude of IPSP/Cs is sustained resulting in an S shaped
      decay time course. This activity-dependent plasticity at GABAergic synapses in
      the rNST is potentially important in the encoding of taste responses because the
      dynamic range of stimulus frequencies that result in synaptic plasticity (0-70
      Hz) corresponds to the breadth of frequencies that travels via afferent gustatory
      nerve fibers in response to taste stimuli.

PMID- 12522171
TI  - Progesterone withdrawal reduces paired-pulse inhibition in rat hippocampus:
      dependence on GABA(A) receptor alpha4 subunit upregulation.
AB  - Withdrawal from the endogenous steroid progesterone (P) after chronic
      administration increases anxiety and seizure susceptibility via declining levels
      of its potent GABA-modulatory metabolite 3alpha-OH-5alpha-pregnan-20-one
      (3alpha,5alphaTHP). This 3alpha,5alpha-THP withdrawal also results in a decreased
      decay time constant for GABA-gated current assessed using whole cell patch-clamp
      techniques on pyramidal cells acutely dissociated from CA1 hippocampus. The
      purpose of this study was to test the hypothesis that the decreases in total
      integrated GABA-gated current observed at the level of the isolated pyramidal
      cell would be manifested as a reduced GABA inhibition at the circuit level
      following hormone withdrawal. Toward this end, adult, female rats were
      administered P via subcutaneous capsule for 3 wk using a multiple withdrawal
      paradigm. We then evaluated paired-pulse inhibition (PPI) of pyramidal neurons in
      CA1 hippocampus using extracellular recording techniques in hippocampal slices
      from rats 24 h after removal of the capsule (P withdrawal, P Wd). The population
      spike (PS) was recorded at the stratum pyramidale following homosynaptic
      orthodromic stimulation in the nearby stratum radiatum. The threshold for
      eliciting a response was decreased after P Wd, and the mean PS amplitude was
      significantly increased compared with control values at this time. Paired pulses
      with 10-ms inter-pulse intervals were then applied across an intensity range from
      2 to 20 times threshold. Evaluation of paired-pulse responses showed a
      significant 40-50% reduction in PPI for PS recorded in the hippocampal CA1 region
      after P Wd, suggesting an increase in circuit excitability. At this time,
      enhancement of PPI by the benzodiazepine lorazepam (LZM; 10 microM) was
      prevented, while pentobarbital (10 microM) potentiation of PPI was comparable to
      control levels of response. These data are consistent with upregulation of the
      alpha4 subunit of the GABA(A) receptor (GABAR) as we have previously shown.
      Moreover, the reduced PPI caused by P Wd was prevented by suppression of GABAR
      alpha4-subunit expression following intraventricular administration of specific
      antisense oligonucleotides (1 microg/h for 72 h). These results demonstrating a
      reduction in PPI following P Wd suggest that GABAergic-mediated recurrent or feed
      forward inhibition occurring at the circuit level were decreased following P Wd
      in female rats, an effect at least partially attributable to alterations in the
      GABAR subunit gene expression.

PMID- 12522173
TI  - Systematic changes in motor cortex cell activity with arm posture during
      directional isometric force generation.
AB  - We report here the activity of 96 cells in primate primary motor cortex (MI)
      during exertion of isometric forces at the hand in constant spatial directions,
      while the hand was at five to nine different spatial locations on a plane. The
      discharge of nearly all cells varied significantly with both hand location and
      the direction of isometric force before and during force-ramp generation as well
      as during static force-hold. In addition, nearly all cells displayed changes in
      the variation of their activity with force direction at different hand locations.
      This change in relationship was often expressed in part as a change in the cell's
      directional tuning at different hand locations. Cell directional tuning tended to
      shift systematically with hand location even though the direction of static force
      output at the hand remained constant. These directional effects were less
      pronounced before the onset of force output than after force onset. Cells also
      often showed planar modulations of discharge level with hand location. Sixteen
      proximal arm muscles showed similar effects, reflecting how hand location
      dependent biomechanical factors altered their task-related activity. These
      findings indicate that MI single-cell activity does not covary exclusively with
      the level and direction of net force output at the hand and provides further
      evidence that MI contributes to the transformation between extrinsic and
      intrinsic representations of motor output during isometric force production.

PMID- 12522174
TI  - Na+ channel expression and neuronal function in the Na+/H+ exchanger 1 null
      mutant mouse.
AB  - Mice lacking Na(+)/H(+) exchanger 1 (NHE1) suffer from recurrent seizures and die
      early postnatally. Although the mechanisms for seizures are not well established,
      our previous electrophysiological work has shown that neuronal excitability and
      Na(+) current density are increased in hippocampal CA1 neurons of these mutant
      mice. However, it is unknown whether this increased density is related to altered
      expression or functional regulation of Na(+) channels. In this work, we asked
      three questions: is the increased excitability limited to CA1 neurons, is the
      increased Na(+) current density related to an increased Na(+) channel expression,
      and, if so, which Na(+) channel subtype(s) is upregulated? Using
      neurophysiological, autoradiographic, and immunoblotting techniques, we showed
      that both CA1 and cortical neurons have an increase in membrane excitability and
      Na(+) current density; Na(+) channel density is selectively upregulated in the
      hippocampus and cortex (P < 0.05); and Na(+) channel subtype I is significantly
      increased in the hippocampus and Na(+) channel subtype II is increased in the
      cortex. Our results demonstrate that mice lacking NHE1 upregulate their Na(+)
      channel expression in the hippocampal and cortical regions selectively; this
      leads to an increase in Na(+) current density and membrane excitability. We
      speculate that neuronal overexcitability due to Na(+) channel upregulation in the
      hippocampus and cortex forms the basis of epileptic seizures in NHE1 mutant mice.

PMID- 12522175
TI  - Effect of adrenalectomy on miniature inhibitory postsynaptic currents in the
      paraventricular nucleus of the hypothalamus.
AB  - Within the rat paraventricular nucleus of the hypothalamus two types of neurons
      have been distinguished based on morphological appearance, i.e., parvocellular
      and magnocellular neurons. The parvocellular neurons play a key role in
      regulating the activity of the hypothalamo-pituitary-adrenal axis, which is
      activated, e.g., after stress exposure. These neurons receive humoral negative
      feedback via the adrenal hormone corticosterone but also neuronal inhibitory
      input, either directly or transsynaptically relayed via GABAergic interneurons.
      In the present study we examined to what extent the neuronal GABAergic input is
      influenced by the humoral signal. To this end, miniature inhibitory postsynaptic
      currents (mIPSCs) were recorded in parvo- and magnocellular neurons of
      adrenalectomized rats, which lack corticosterone, and in sham-operated controls.
      Under visual control neurons in coronal slices containing the paraventricular
      nucleus were designated as putative parvocellular or magnocellular neurons: the
      former were located in the medial part of the nucleus and displayed a small
      fusiform soma; the latter were mostly located in the lateral part and were
      recognized by their large round soma. Compared with putative magnocellular
      neurons, parvocellular neurons generally exhibited a lower membrane capacitance,
      lower mIPSC frequency, and smaller mIPSC amplitude. Following adrenalectomy, the
      mIPSC frequency was significantly enhanced in parvo- but not magnocellular
      neurons. Other properties of the cells were not affected. In a second series of
      experiments we examined whether the increase in mIPSC frequency was due to the
      absence of corticosterone or caused by other effects related to adrenalectomy.
      The data support the former explanation since implantation of a corticosterone
      releasing pellet after adrenalectomy fully prevented the change in mIPSC
      frequency. We conclude that, in the absence of humoral negative feedback, local
      GABAergic input of parvocellular neurons in the paraventricular nucleus is
      enhanced. This may provide a compensatory mechanism necessary for maintaining
      controllable network activity.

PMID- 12522176
TI  - Functional organization of speed tuned neurons in visual area MT.
AB  - We analyzed the functional organization of speed tuned neurons in extrastriate
      visual area MT. We sought to determine whether neurons tuned for particular
      speeds are clustered spatially and whether such spatial clusters are elongated
      normal to the cortical surface so as to form speed columns. Our data showed that
      MT neurons are indeed clustered according to preferred speed. Multiunit
      recordings were speed tuned, and the speed tuning of these signals was well
      correlated with the speed tuning of single neurons recorded simultaneously. To
      determine whether speed columns exist in MT, we compared the rates at which
      preferred speed changed in electrode tracks that traversed MT obliquely and
      normally to the cortical surface. If speed columns exist, the preferred speed
      should change at a faster rate during oblique electrode tracks. We found,
      however, that preferred speed changed at similar rates for either type of
      penetration. In the same data set, the rate of change of preferred direction and
      preferred disparity differed substantially in normal and oblique penetrations as
      expected from the known columnar organization of MT. Thus our results suggest
      that a columnar organization for speed tuned neurons does not exist in MT.

PMID- 12522177
TI  - GABA-mediated inhibition of glutamate release during ischemia in substantia
      gelatinosa of the adult rat.
AB  - An ischemia-induced change in glutamatergic transmission was investigated in
      substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the
      whole cell patch-clamp technique; the ischemia was simulated by superfusing an
      oxygen- and glucose-free medium (ISM). Following ISM superfusion, 21 of 37 SG
      neurons tested produced an outward current (23 +/- 4 pA at a holding potential of
      -70 mV), which was followed by a slow and subsequent rapid inward current; the
      remaining neurons had only inward currents. During such a change in holding
      currents, spontaneous excitatory postsynaptic currents (EPSCs) were remarkably
      decreased in a frequency with time (half-decay time of the frequency: about 65
      s). The frequency of spontaneous EPSCs was reduced to 28 +/- 13% (n = 37) of the
      control level during the generation of the slow inward current (about 4 min after
      the beginning of ISM superfusion) without a change in the amplitude of
      spontaneous EPSCs. When ISM was superfused together with either bicuculline (10
      microM) or CGP35348 (20 microM; GABA(A) and GABA(B) receptor antagonists,
      respectively), spontaneous EPSC frequency reduced by ISM recovered to the control
      level and then the frequency markedly increased [by 325 +/- 120% (n = 22) and 326
      +/- 91% (n = 17), respectively, 4 min after ISM superfusion]; this alteration in
      the frequency was not accompanied by a change in spontaneous EPSC amplitude.
      Superfusing TTX (1 microM)-containing ISM resulted in a similar recovery of
      spontaneous EPSC frequency and following increase (by 328 +/- 26%, n = 12) in the
      frequency; strychnine (1 microM) did not affect ISM-induced changes in
      spontaneous EPSC frequency (n = 5). It is concluded that the ischemic simulation
      inhibits excitatory transmission to SG neurons, whose action is in part mediated
      by the activation of presynaptic GABA(A) and GABA(B) receptors, probably due to
      GABA released from interneurons as a result of an ischemia-induced increase in
      neuronal activities. This action might protect SG neurons from an excessive
      excitation mediated by L-glutamate during ischemia.

PMID- 12522178
TI  - Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus
      in rats.
AB  - Extracellular action potentials were recorded from 73 neurons in the
      parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus
      of anesthetized Wistar rats during gustatory, thermal, and tactile stimulation of
      the whole oral cavity. The stimulus array consisted of 16 room-temperature (23
      degrees C) sapid stimuli, distilled water at three temperatures (0, 23, and 37
      degrees C), and 0.1 M NaCl at three temperatures (0, 23, and 37 degrees C). Among
      all 151 neurons isolated in VPMpc, 9% responded exclusively to taste, 33% to
      taste and temperature, none to taste and touch, but 6% to all three modalities.
      Discharge rates evoked by the basic tastants were 13.8 +/- 1.6 (SD) spikes/s for
      0.1 M NaCl, 9.3 +/- 1.4 spikes/s for 0.01 M HCl, 5.1 +/- 0.9 spikes/s for 0.5 M
      sucrose, and 4.3 +/- 0.6 spikes/s for 0.01 M quinine HCl. Water evoked mean
      responses at 0, 23, and 37 degrees C of 9.9 +/- 1.5, 0.6 +/- 0.4, and 1.3 +/- 0.9
      spikes/s, respectively. The mean firing rate evoked by 37 and 0 degrees C NaCl
      was 15.0 +/- 2.4 and 17.0 +/- 2.8 spikes/s, respectively. The exponent of the
      NaCl concentration-response power function was 0.39. Thalamic taste cells were
      broadly tuned. The mean breadth-of-tuning coefficient for these 73 gustatory
      cells was 0.79 +/- 0.02. Two cells responded predominantly with inhibition, which
      accounted for the majority of inhibitory responses. The taste neurons were
      statistically divisible into three groups: sodium-oriented (n = 40), acid
      oriented (n = 12), and sugar-oriented (n = 17). Four additional bitter-oriented
      neurons were not closely enough related to be defined as a group and were
      considered outliers. The sodium-oriented group could be divided into three
      statistically distinct subgroups, differing in the specificity of their responses
      to NaCl. With respect to polymodal sensitivity, spontaneous rate, evoked response
      rates, signal-to-noise ratio, proportions of cells responding best to basic
      tastants, taste neuron groups, taste spaces, and temporal responses, VPMpc
      neurons have characteristics that are intermediate between those of parabrachial
      and cortical gustatory neurons.

PMID- 12522179
TI  - Coordinated turn-and-reach movements. I. Anticipatory compensation for self
      generated coriolis and interaction torques.
AB  - When reaching movements involve simultaneous trunk rotation, additional
      interaction torques are generated on the arm that are absent when the trunk is
      stable. To explore whether the CNS compensates for such self-generated
      interaction torques, we recorded hand trajectories in reaching tasks involving
      various amplitudes and velocities of arm extension and trunk rotation. Subjects
      pointed to three targets on a surface slightly above waist level. Two of the
      target locations were chosen so that a similar arm configuration relative to the
      trunk would be required for reaching to them, one of these targets requiring
      substantial trunk rotation, the other very little. Significant trunk rotation was
      necessary to reach the third target, but the arm's radial distance to the body
      remained virtually unchanged. Subjects reached at two speeds-a natural pace
      (slow) and rapidly (fast)-under normal lighting and in total darkness. Trunk
      angular velocity and finger velocity relative to the trunk were higher in the
      fast conditions but were not affected by the presence or absence of vision. Peak
      trunk velocity increased with increasing trunk rotation up to a maximum of 200
      degrees /s. In slow movements, peak finger velocity relative to the trunk was
      smaller when trunk rotation was necessary to reach the targets. In fast
      movements, peak finger velocity was approximately 1.7 m/s for all targets. Finger
      trajectories were more curved when reaching movements involved substantial trunk
      rotation; however, the terminal errors and the maximal deviation of the
      trajectory from a straight line were comparable in slow and fast movements. This
      pattern indicates that the larger Coriolis, centripetal, and inertial interaction
      torques generated during rapid reaches were compensated by additional joint
      torques. Trajectory characteristics did not vary with the presence or absence of
      vision, indicating that visual feedback was unnecessary for anticipatory
      compensations. In all reaches involving trunk rotation, the finger movement
      generally occurred entirely during the trunk movement, indicating that the CNS
      did not minimize Coriolis forces incumbent on trunk rotation by sequencing the
      arm and trunk motions into a turn followed by a reach. A simplified model of the
      arm/trunk system revealed that additional interaction torques generated on the
      arm during voluntary turning and reaching were equivalent to < or =1.8 g (1 g =
      9.81 m/s(2)) of external force at the elbow but did not degrade performance. In
      slow-rotation room studies involving reaching movements during passive rotation,
      Coriolis forces as small as 0.2 g greatly deflect movement trajectories and
      endpoints. We conclude that compensatory motor innervations are engaged in a
      predictive fashion to counteract impending self-generated interaction torques
      during voluntary reaching movements.

PMID- 12522180
TI  - Coordinated turn-and-reach movements. II. Planning in an external frame of
      reference.
AB  - The preceding study demonstrated that normal subjects compensate for the
      additional interaction torques generated when a reaching movement is made during
      voluntary trunk rotation. The present paper assesses the influence of trunk
      rotation on finger trajectories and on interjoint coordination and determines
      whether simultaneous turn-and-reach movements are most simply described relative
      to a trunk-based or an external reference frame. Subjects reached to targets
      requiring different extents of arm joint and trunk rotation at a natural pace and
      quickly in normal lighting and in total darkness. We first examined whether the
      larger interaction torques generated during rapid turn-and-reach movements
      perturb finger trajectories and interjoint coordination and whether visual
      feedback plays a role in compensating for these torques. These issues were
      addressed using generalized Procrustes analysis (GPA), which attempts to overlap
      a group of configurations (e.g., joint trajectories) through translations and
      rotations in multi-dimensional space. We first used GPA to identify the mean
      intrinsic patterns of finger and joint trajectories (i.e., their average shape
      irrespective of location and orientation variability in the external and joint
      workspaces) from turn-and-reach movements performed in each experimental
      condition and then calculated their curvatures. We then quantified the
      discrepancy between each finger or joint trajectory and the intrinsic pattern
      both after GPA was applied individually to trajectories from a pair of
      experimental conditions and after GPA was applied to the same trajectories pooled
      together. For several subjects, joint trajectories but not finger trajectories
      were more curved in fast than slow movements. The curvature of both joint and
      finger trajectories of turn-and-reach movements was relatively unaffected by the
      vision conditions. Pooling across speed conditions significantly increased the
      discrepancy between joint but not finger trajectories for most subjects,
      indicating that subjects used different patterns of interjoint coordination in
      slow and fast movements while nevertheless preserving the shape of their finger
      trajectory. Higher movement speeds did not disrupt the arm joint rotations
      despite the larger interaction torques generated. Rather, subjects used the
      redundant degrees of freedom of the arm/trunk system to achieve similar finger
      trajectories with differing joint configurations. We examined finger movement
      patterns and velocity profiles to determine the frame of reference in which turn
      and-reach movements could be most simply described. Finger trajectories of turn
      and-reach movements had much larger curvatures and their velocity profiles were
      less smooth and less bell-like in trunk-based coordinates than in external
      coordinates. Taken together, these results support the conclusion that turn-and
      reach movements are controlled in an external frame of reference.

PMID- 12522181
TI  - Modulation of transmission in the corticospinal and group Ia afferent pathways to
      soleus motoneurons during bicycling.
AB  - Transmission in the corticospinal and Ia pathways to soleus motoneurons was
      investigated in healthy human subjects during bicycling. Soleus H reflexes and
      motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) were
      modulated similarly during the crank cycle being large during downstroke
      [concomitant with soleus background electromyographic (EMG) activity] and small
      during upstroke. Tibialis anterior MEPs were in contrast large during upstroke
      and small during downstroke. The soleus H reflexes and MEPs were also recorded
      during tonic plantarflexion at a similar ankle joint position, corresponding
      ankle angle, and matched background EMG activity as during the different phases
      of bicycling. Relative to their size during tonic plantarflexion, the MEPs were
      found to be facilitated in the early part of downstroke during bicycling, whereas
      the H reflexes were depressed in the late part of downstroke. The intensity of
      TMS was decreased below MEP threshold and used to condition the soleus H reflex.
      At short intervals (conditioning-test intervals of -3 to -1 ms), TMS produced a
      facilitation of the H reflex that is in all likelihood caused by activation of
      the fast monosynaptic corticospinal pathway. This facilitation was significantly
      larger in the early part of downstroke during bicycling than during tonic
      plantarflexion. This suggests that the increased MEP during downstroke was caused
      by changes in transmission in the fast monosynaptic corticospinal pathway. To
      investigate whether the depression of H reflexes in the late part of downstroke
      was caused by increased presynaptic inhibition of Ia afferents, the soleus H
      reflex was conditioned by stimulation of the femoral nerve. At a short interval
      (conditioning-test interval: -7 to -5 ms), the femoral nerve stimulation produced
      a facilitation of the H reflex that is mediated by the heteronymous monosynaptic
      Ia pathway from the femoral nerve to soleus motoneurons. Within the initial 0.5
      ms after its onset, the size of this facilitation depends on the level of
      presynaptic inhibition of the Ia afferents, which mediate the facilitation. The
      size of the facilitation was strongly depressed in the late part of downstroke,
      compared with the early part of downstroke, suggesting that increased presynaptic
      inhibition was indeed responsible for the depression of the H reflex. These
      findings suggest that there is a selectively increased transmission in the fast
      monosynaptic corticospinal pathway to soleus motoneurons in early downstroke
      during bicycling. It would seem likely that one cause of this is increased
      excitability of the involved cortical neurons. The increased presynaptic
      inhibition of Ia afferents in late downstroke may be of importance for depression
      of stretch reflex activity before and during upstroke.

PMID- 12522183
TI  - Persistent Na+ current modifies burst discharge by regulating conditional
      backpropagation of dendritic spikes.
AB  - The estimation and detection of stimuli by sensory neurons is affected by factors
      that govern a transition from tonic to burst mode and the frequency
      characteristics of burst output. Pyramidal cells in the electrosensory lobe of
      weakly electric fish generate spike bursts for the purpose of stimulus detection.
      Spike bursts are generated during repetitive discharge when a frequency-dependent
      broadening of dendritic spikes increases current flow from dendrite to soma to
      potentiate a somatic depolarizing afterpotential (DAP). The DAP eventually
      triggers a somatic spike doublet with an interspike interval that falls inside
      the dendritic refractory period, blocking spike backpropagiation and the DAP.
      Repetition of this process gives rise to a rhythmic dendritic spike failure,
      termed conditional backpropagation, that converts cell output from tonic to burst
      discharge. Through in vitro recordings and compartmental modeling we show that
      burst frequency is regulated by the rate of DAP potentiation during a burst,
      which determines the time required to discharge the spike doublet that blocks
      backpropagation. DAP potentiation is magnified through a positive feedback
      process when an increase in dendritic spike duration activates persistent sodium
      current (I(NaP)). I(NaP) further promotes a slow depolarization that induces a
      shift from tonic to burst discharge over time. The results are consistent with a
      dynamical systems analysis that shows that the threshold separating tonic and
      burst discharge can be represented as a saddle-node bifurcation. The interaction
      between dendritic K(+) current and I(NaP) provides a physiological explanation
      for a variable time scale of bursting dynamics characteristic of such a
      bifurcation.

PMID- 12522182
TI  - Postnatal maturational changes in rat pelvic autonomic ganglion cells: a mixture
      of steroid-dependent and -independent effects.
AB  - Androgens have potent effects on the maturation and maintenance of a number of
      neural pathways involved in reproductive behaviors in males. Most studies in this
      area have focused on central pathways, but androgen receptors are expressed by
      many peripheral neurons innervating reproductive organs, and previous studies
      have demonstrated structural and chemical changes in these neurons at puberty and
      after castration. We have performed the first electrophysiological comparison of
      pelvic autonomic ganglion neurons in male rats before and after puberty and
      following pre- or postpubertal castration. Studies were performed in vitro on
      intact ganglia with hypogastric and pelvic nerves attached to allow synaptic
      activation of sympathetic or parasympathetic neurons, respectively. Pelvic
      ganglion neurons underwent many changes in their passive and active membrane
      properties over the pubertal period, and some of these changes were dependent on
      exposure to circulating androgens. The most pronounced steroid-dependent effects
      were on membrane capacitance (soma size) in sympathetic neurons and duration of
      the action potential afterhyperpolarization in tonic neurons. Our study also
      showed that rat pelvic ganglion cells and their synaptic inputs were more diverse
      than previously reported. In conclusion, this study demonstrated that rat pelvic
      ganglion neurons undergo considerable postnatal changes in their
      electrophysiological properties. The steroid dependence of some of these changes
      indicates that circulating androgens may influence reproductive behaviors at many
      locations within the nervous system not just in the brain and spinal cord.

PMID- 12522184
TI  - Three-dimensional eye position and slow phase velocity in humans with downbeat
      nystagmus.
AB  - Downbeat nystagmus (DN), a fixation nystagmus with the fast phases directed
      downward, is usually caused by cerebellar lesions, but the precise etiology is
      not known. A disorder of the smooth-pursuit system or of central vestibular
      pathways has been proposed. However, both hypotheses fail to explain why DN is
      usually accompanied by gaze-holding nystagmus, which implies a leaky neural
      velocity-to-position integrator. Because three-dimensional (3-D) analysis of
      nystagmus slow phases provides an excellent means for testing both hypotheses, we
      examined 19 patients with DN during a fixation task and compared them with
      healthy subjects. We show that the presentation of DN patients is not uniform;
      they can be grouped according to their deficits: DN with vertical integrator
      leakage, DN with vertical and horizontal integrator leakage, and DN without
      integrator leakage. The 3-D analysis of the slow phases of DN patients revealed
      that DN is most likely neither caused by damage to central vestibular pathways
      carrying semicircular canal information nor by a smooth pursuit imbalance. We
      propose that the observed effects can be explained by partial damage of a brain
      stem-cerebellar loop that augments the time constant of the neural velocity to
      position integrators in the brain stem and neurally adjusts the orientation of
      Listing's plane.

PMID- 12522185
TI  - Eye movements during multi-axis whole-body rotations.
AB  - The semi-circular canals and the otolith organs both contribute to gaze
      stabilization during head movement. We investigated how these sensory signals
      interact when they provide conflicting information about head orientation in
      space. Human subjects were reoriented 90 degrees in pitch or roll during long
      duration, constant-velocity rotation about the earth-vertical axis while we
      measured three-dimensional eye movements. After the reorientation, the otoliths
      correctly indicated the static orientation of the subject with respect to
      gravity, while the semicircular canals provided a strong signal of rotation. This
      rotation signal from the canals could only be consistent with a static
      orientation with respect to gravity if the rotation-axis indicated by the canals
      was exactly parallel to gravity. This was not true, so a cue-conflict existed.
      These conflicting stimuli elicited motion sickness and a complex tumbling
      sensation. Strong horizontal, vertical, and/or torsional eye movements were also
      induced, allowing us to study the influence of the conflict between the otoliths
      and the canals on all three eye-movement components. We found a shortening of the
      horizontal and vertical time constants of the decay of nystagmus and a trend for
      an increase in peak velocity following reorientation. The dumping of the velocity
      storage occurred regardless of whether eye velocity along that axis was
      compensatory to the head rotation or not. We found a trend for the axis of eye
      velocity to reorient to make the head-velocity signal from the canals consistent
      with the head-orientation signal from the otoliths, but this reorientation was
      small and only observed when subjects were tilted to upright. Previous models of
      canal-otolith interaction could not fully account for our data, particularly the
      decreased time constant of the decay of nystagmus. We present a model with a
      mechanism that reduces the velocity-storage component in the presence of a strong
      cue-conflict. Our study, supported by other experiments, also indicates that
      static otolith signals exhibit considerably smaller effects on eye movements in
      humans than in monkeys.

PMID- 12522186
TI  - Corticofugal modulation on both ON and OFF responses in the nonlemniscal auditory
      thalamus of the guinea pig.
AB  - Corticofugal modulation on both ON and OFF responses in various nuclei in the
      medial geniculate body (MGB) was examined by locally activating the auditory
      cortex and looking for effects on the neuronal responses to acoustic stimuli. In
      contrast with a major corticofugal facilitatory effect on the ON neurons in the
      lemniscal nucleus of the MGB of the guinea pigs, of 132 ON neurons tested in
      three conditions with cortical activation through each of three implanted
      electrodes, the majority of the tested conditions (319/396) that were sampled
      from the nonlemniscal nuclei of the MGB received inhibitory modulation from the
      activated cortex. This inhibitory effect was >50% for 99 cases while the auditory
      cortex was activated. Most of the OFF and ON-OFF MGB neurons (44/54) showed a
      facilitatory effect of 111.4 +/- 99.9%, and three showed a small inhibitory
      effect of 25.7 +/- 5.8% on their OFF responses. Thirty neurons in the border
      region between the lemniscal and nonlemniscal MGB showed mainly facilitatory
      corticofugal effects on both ON and OFF responses. Meanwhile, cortical
      stimulation induced almost exclusive inhibitory effects on the ON response and
      facilitatory effects on the OFF response in the MGcm. It is suggested that the
      OFF response is produced as a disinhibition from the inhibitory input of the
      auditory stimulus. The present results provide a possible explanation for
      selective gating of the auditory information through the lemniscal MGB while
      switching off other unwanted sensory signals and the interference from the limbic
      system, leaving the other auditory cortex prepared to process only the auditory
      signal.

PMID- 12522187
TI  - Excitatory synaptic currents in lumbosacral parasympathetic preganglionic neurons
      evoked by stimulation of the dorsal commissure.
AB  - Excitatory pathways from the dorsal commissure (DCM) to L(6)-S(1) parasympathetic
      preganglionic neurons (PGN) were examined using whole-cell patch-clamp recording
      techniques in spinal cord slices from neonatal rats. PGN were identified by
      retrograde axonal transport of a fluorescent dye injected into the
      intraperitoneal space. Excitatory postsynaptic currents (EPSCs) were evoked in
      PGN by stimulation of DCM in the presence of bicuculline methiodide (10 microM)
      and strychnine (1 microM) to block inhibitory pathways. Electrical stimulation of
      DCM evoked two types of inward currents. In the majority of PGN (n = 66),
      currents (mean amplitude, 47.9 +/- 4.7 pA) occurred at a short and relatively
      constant latency (3.8 +/- 0.1 ms) and presumably represent monosynaptic EPSCs
      (Type 1). However, in other neurons (n = 20), a different type of EPSC (Type 2)
      was noted, consisting of a fast monosynaptic component followed by a prolonged
      inward current with superimposed fast transients presumably representing
      excitatory inputs mediated by polysynaptic pathways. Type 1 EPSCs were
      pharmacologically dissected into two components. A fast component was blocked by
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 microM) and a slowly decaying
      component was blocked by 2-amino-5-phosphonovalerate (APV, 50 microM). The fast
      component of Type 1 EPSCs had a linear current-voltage relationship and reversed
      at a membrane potential of -7.6 +/- 1.3 mV (n = 5). The fast component of Type 2
      EPSCs was also blocked by 5 microM CNQX and the remaining slower component was
      blocked by 50 microM APV. When the DCM was stimulated in the presence of 50
      microM APV, the time to peak and decay time constant in Type 1 EPSCs were 1.9 +/-
      0.2 and 4.1 +/- 0.8 ms, respectively. Examination of the NMDA receptor-mediated
      component of the EPSCs in the presence of 5 microM CNQX revealed a current
      voltage relationship that had a region of negative slope conductance (from -20 to
      -80 mV), which was abolished in Mg(2+)-free external solution. The time to peak
      and decay time constant of this component were 14.2 +/- 2.0 and 91.0 +/- 12.4 ms,
      respectively. Type 1 EPSCs in some PGN responded in an all-or-none manner and
      presumably represented unitary synaptic responses; whereas Type 2 EPSCs always
      exhibited a graded stimulus intensity-response relationship. Paired-pulse
      facilitation (50-ms interstimulus intervals; 141 +/- 5.6% increase, n = 8) of
      EPSCs was observed. These results indicate that PGN receive monosynaptic and
      polysynaptic glutamatergic excitatory inputs from neurons and/or axonal pathways
      in the DCM.

PMID- 12522188
TI  - Neural processing of gravito-inertial cues in humans. IV. Influence of visual
      rotational cues during roll optokinetic stimuli.
AB  - Sensory systems often provide ambiguous information. For example, otolith organs
      measure gravito-inertial force (GIF), the sum of gravitational force and inertial
      force due to linear acceleration. However, according to Einstein's equivalence
      principle, a change in gravitational force due to tilt is indistinguishable from
      a change in inertial force due to translation. Therefore the central nervous
      system (CNS) must use other sensory cues to distinguish tilt from translation.
      For example, the CNS might use dynamic visual cues indicating rotation to help
      determine the orientation of gravity (tilt). This, in turn, might influence the
      neural processes that estimate linear acceleration, since the CNS might estimate
      gravity and linear acceleration such that the difference between these estimates
      matches the measured GIF. Depending on specific sensory information inflow,
      inaccurate estimates of gravity and linear acceleration can occur. Specifically,
      we predict that illusory tilt caused by roll optokinetic cues should lead to a
      horizontal vestibuloocular reflex compensatory for an interaural estimate of
      linear acceleration, even in the absence of actual linear acceleration. To
      investigate these predictions, we measured eye movements binocularly using
      infrared video methods in 17 subjects during and after optokinetic stimulation
      about the subject's nasooccipital (roll) axis (60 degrees /s, clockwise or
      counterclockwise). The optokinetic stimulation was applied for 60 s followed by
      30 s in darkness. We simultaneously measured subjective roll tilt using a
      somatosensory bar. Each subject was tested in three different orientations:
      upright, pitched forward 10 degrees, and pitched backward 10 degrees. Five
      subjects reported significant subjective roll tilt (>10 degrees ) in directions
      consistent with the direction of the optokinetic stimulation. In addition to
      torsional optokinetic nystagmus and after nystagmus, we measured a horizontal
      nystagmus to the right during and following clockwise (CW) stimulation and to the
      left during and following counterclockwise (CCW) stimulation. These measurements
      match predictions that subjective tilt in the absence of real tilt should induce
      a nonzero estimate of interaural linear acceleration and, therefore, a horizontal
      eye response. Furthermore, as predicted, the horizontal response in the dark was
      larger for Tilters (n = 5) than for Non-Tilters (n = 12).

PMID- 12522189
TI  - Effects of altering initial position on movement direction and extent.
AB  - The purpose of this study was to examine the relative influence of initial hand
      location on the direction and extent of planar reaching movements. Subjects
      performed a horizontal-plane reaching task with the dominant arm supported above
      a table top by a frictionless air-jet system. A start circle and a target were
      reflected from a horizontal projection screen onto a horizontally positioned
      mirror, which blocked the subject's view of the arm. A cursor, representing
      either actual or virtual finger location, was only displayed between each trial
      to allow subjects to position the cursor in the start circle. Prior to occasional
      "probe trials," we changed the start location of the finger relative to the
      cursor. Subjects reported being unaware of the discrepancy between cursor and
      finger. Our results indicate that regardless of initial hand location, subjects
      did not alter the direction of movement. However, movement distance was
      systematically adjusted in accord with the baseline target position. Thus when
      the hand start position was perpendicularly displaced relative to the target
      direction, neither the direction nor the extent of movement varied relative to
      that of baseline. However, when the hand was displaced along the target
      direction, either anterior or posterior, movements were made in the same
      direction as baseline trials but were shortened or lengthened, respectively. This
      effect was asymmetrical such that movements from anterior displaced positions
      showed greater distance adjustment than those from posterior displaced positions.
      Inverse dynamic analysis revealed substantial changes in elbow and shoulder
      muscle torque strategies for both right/left and anterior/posterior pairs of
      displacements. In the case of right/left displacements, such changes in muscle
      torque compensated changes in limb configuration such that movements were made in
      the same direction and to the same extent as baseline trials. Our results support
      the hypothesis that movement direction is specified relative to an origin at the
      current location of the hand. Movement extent, on the other hand, appears to be
      affected by the workspace learned during baseline movement experience.

PMID- 12522191
TI  - Convulsant and anticonvulsant effects on spontaneous CA3 population bursts.
AB  - This paper analyzes the effects of a convulsant and an anticonvulsant
      manipulation on spontaneous bursts in CA3 pyramidal cells in the in vitro slice
      preparation under conditions of low (3.3 mM [K(+)](o)) and high (8.5 mM
      [K(+)](o)) burst probability. When burst probability was low, the anticonvulsant,
      pentobarbital, produced the anticipated effects: the burst duration decreased and
      interburst interval increased. However, when burst probability was high, both
      anticonvulsant and convulsant manipulations decreased the interburst interval and
      the burst duration. To reconcile these findings, we utilized a model in which CA3
      burst duration is limited by activity-dependent depression of CA3 excitatory
      recurrent collateral synapses and the interburst interval is determined by the
      time required to recover from this depression. We defined the burst end threshold
      as the level of synaptic depression at which bursts terminate, and the burst
      start threshold as the level of synaptic depression at which burst initiation is
      possible. Synapses were considered to oscillate between these thresholds. When
      average burst duration and interburst interval data were fit using this model,
      the paradoxically similar effects of the convulsant and anticonvulsant
      manipulations could be quantitatively interpreted. The convulsant maneuver
      decreased both the burst start and end thresholds. The start threshold decreased
      more than the end threshold, so that the thresholds were closer together. This
      decreased the time needed to transition from one threshold to the other, i.e.,
      the interburst interval and burst duration. The anticonvulsant manipulation
      primarily increased the burst end threshold. This also decreased the difference
      between thresholds, decreasing both interburst interval and burst duration. This
      model resolves the paradoxical proconvulsant effects of pentobarbital in the CA3
      preparation and provides insights into the effects of anticonvulsants on
      epileptiform discharges in the human EEG.

PMID- 12522190
TI  - Windup of flexion reflexes in chronic human spinal cord injury: a marker for
      neuronal plateau potentials?
AB  - The physiological basis of flexion spasms in individuals after spinal cord injury
      (SCI) may involve alterations in the properties of spinal neurons in the flexion
      reflex pathways. We hypothesize that these changes would be manifested as
      progressive increases in reflex response with repetitive stimulus application
      (i.e., "windup") of the flexion reflexes. We investigated the windup of flexion
      reflex responses in 12 individuals with complete chronic SCI. Flexion reflexes
      were triggered using trains of electrical stimulation of plantar skin at variable
      intensities and inter-stimulus intervals. For threshold and suprathreshold
      stimulation, windup of both peak ankle and hip flexion torques and of integrated
      tibialis anterior electromyographic activity was observed consistently in all
      patients at inter-stimulus intervals < or =3 s. For subthreshold stimuli,
      facilitation of reflexes occurred only at intervals < or =1 s. Similarly, the
      latency of flexion reflexes decreased significantly at intervals < or =1 s.
      Patients that were receiving anti-spasticity medications (e.g., baclofen) had
      surprisingly larger windup of reflex responses than those who did not take such
      medications, although this difference may be related to differences of spasm
      frequency between the groups of subjects. The results indicate that the increase
      in spinal neuronal excitability following a train of electrical stimuli lasts for
      < or =3 s, similar to previous studies of nociceptive processing. Such long
      lasting increases in flexion reflex responses suggest that cellular mechanisms
      such as plateau potentials in spinal motoneurons, interneurons, or both, may
      partially mediate spinal cord hyperexcitability in the absence of descending
      modulatory input.

PMID- 12522192
TI  - Characterization of spindle afferents in rat soleus muscle using ramp-and-hold
      and sinusoidal stretches.
AB  - The discharge properties of 51 afferents were studied in the rat soleus muscle
      spindles. Under deep anesthesia using a pentobarbital sodium solution (30 mg/kg),
      a laminectomy was performed and the right L(4) and L(5) dorsal and ventral roots
      were transected near their entry into the spinal cord. In situ, the minimal
      (L(min)) muscle length [3 +/- 0.08 (SE) cm] of the soleus was measured at full
      ankle extension. Unitary potentials from the L(5) dorsal root were recorded in
      response to ramp-and-hold stretches applied at 3 mm (S3) and 4 mm (S4) amplitudes
      and four stretch velocities (6, 10, 15, and 30 mm/s), sinusoidal stretches
      performed at four amplitudes (0.12, 0.25, 0.5, and 1 mm) and six stretch
      frequencies (0.5, 1, 2, 3, 6, and 10 Hz), and vibrations applied at 50-, 100-,
      and 150-Hz frequencies. These two kinds of stretches were performed at three
      different muscle lengths (L(min+10%), L(min+15%), and L(min+20%)), whereas
      vibrations were applied at L(min+20%) muscle length. Conduction velocity of the
      fibers was calculated but did not allow to discriminate different fiber types.
      However, the mean conduction velocity of the first fiber group (43.3 +/- 0.8 m/s)
      was significantly higher than that of the second fiber group (33.9 +/- 0.9 m/s).
      Three parameters allowed to differentiate the responses of primary and secondary
      endings: the dynamic index (DI), the discharge during the stretch release from
      the ramp-and-hold stretches, and the linear range and the vibration sensitivity
      from sinusoidal stretches. The slope histogram of the linear regression based on
      the DI and the stretch velocity was clearly bimodal. Therefore the responses were
      separated into two groups. During the stretch release at a velocity of 3 mm/s,
      the first response group (n = 26) exhibited a pause, whereas the second (n = 25)
      did not. The linear range of the second ending group (0.12-1 mm) was broader than
      that of the first (0.12-0.25 mm). The first ending group showed a higher
      sensitivity to high-vibration frequencies of small amplitude than the second. In
      comparison with the literature, we can assert that the first and the second
      ending groups corresponded to the primary and secondary endings, respectively. In
      conclusion, our study showed that in rat soleus muscle spindles, it was possible
      to immediately classify the discharge of Ia and II fibers by using some
      parameters measured under ramp-and-hold and sinusoidal stretches.

PMID- 12522193
TI  - Using arm configuration to learn the effects of gyroscopes and other devices.
AB  - Previous studies have perturbed the association between motor commands and arm
      movements by applying forces to the arm during two-dimensional movements. These
      studies have revealed that, when the normal hand path is perturbed, subjects
      gradually adapt their motor commands to return to this path. The present study
      used the spin of a gyroscope to create a complex perturbation, as subjects
      reached to targets presented in three dimensions. Hand path did not change, but
      the whole-arm geometry ("arm configuration" in four dimensions) was altered. Over
      a series of several hundred reaches to various targets, subjects gradually
      returned the arm movement to its normal configuration. Furthermore, during the
      course of this learning, subjects used a strategy that involved manipulating arm
      posture. A similar strategy was observed when subjects made reaching movements
      with a rod attached to the upper arm to change its inertial characteristics. In
      both cases, the gradual return to the normal arm movement was accomplished
      without an increase in kinetic energy, suggesting that arm postures and movements
      (kinematics) and muscular forces (kinetics) may be mutually optimized. In
      contrast to previous studies, the present results highlight the role of arm
      configuration (rather than hand path) in learning and control.

PMID- 12522194
TI  - Modulation of cortical activity during different imitative behaviors.
AB  - Imitation is a basic form of motor learning during development. We have a
      preference to imitate the actions of others as if looking in a mirror (specular
      imitation: i.e., when the actor moves the left hand, the imitator moves the right
      hand) rather than with the anatomically congruent hand (anatomic imitation: i.e.,
      actor and imitator both moving the right hand). We hypothesized that this
      preference reflects changes in activity in previously described frontoparietal
      cortical areas involved in directly matching observed and executed actions
      (mirror neuron areas). We used functional magnetic resonance imaging to study
      brain activity in normal volunteers imitating left and right hand movements with
      their right hand. Bilateral inferior frontal and right posterior parietal cortex
      were more active during specular imitation compared with anatomic imitation and
      control motor tasks. Furthermore this same pattern of activity was also observed
      in the rostral part of the supplementary motor area (SMA-proper) of the right
      hemisphere. These findings suggest that the degree of involvement of
      frontoparietal mirror areas in imitation depends on the nature of the imitative
      behavior, ruling out a linguistic mediation of these areas in imitation.
      Moreover, activity in the SMA appears to be tightly coupled to frontoparietal
      mirror areas when subjects copy the actions of others.

PMID- 12522195
TI  - Selectivity for conspecific song in the zebra finch auditory forebrain.
AB  - The selectivity of neurons in the zebra finch auditory forebrain for natural
      sounds was investigated systematically. The principal auditory forebrain area in
      songbirds consists of the tonotopically organized field L complex, which, by its
      location in the auditory processing stream, can be compared with the auditory
      cortex of mammals. We also recorded from a secondary auditory area, cHV. Field L
      and cHV are auditory processing stages that are presynaptic to the specialized
      song system nuclei where auditory neurons show an extremely selective response
      for the bird's own song, but weak response to almost any other sounds, including
      conspecific songs. In our study, we found that neurons in field L and cHV had
      stronger responses to conspecific song than to synthetic sounds that were
      designed to match the lower order acoustical properties of song, such as their
      overall power spectra and AM spectra. Such preferential responses to natural
      sounds cannot be explained by linear frequency tuning or simple nonlinear
      intensity tuning and requires linear or nonlinear spectro-temporal neuronal
      transfer functions tuned to the acoustical properties of song. The selectivity
      for conspecific songs in field L and cHV might reflect an intermediate auditory
      processing stage for vocalizations that then contributes to the generation of the
      very specific selectivity for the bird's own song seen in the postsynaptic song
      system.

PMID- 12522196
TI  - Spatiotemporal patterns of excitation and inhibition evoked by the horizontal
      network in layer 2/3 of ferret visual cortex.
AB  - The horizontal network in visual cortex layer 2/3 is implicated in numerous
      psychophysical and physiological properties. To investigate the spatial and
      temporal distribution of excitation and inhibition evoked by this network, we
      used voltage-sensitive dyes to image the responses to focal electrical
      stimulation in tangential slices of ferret visual cortex layer 2/3. The resulting
      optical patterns included a diffuse zone of activation near the stimulation site
      and numerous ovoid domains throughout the slice. In contrast to the fixed anatomy
      of the horizontal connections, substantial shifts in both space and time were
      evident in the distribution of population-based neuronal activity during stimulus
      trains. Both of these shifts relied on inhibitory synaptic potentials, suggesting
      that inhibition driven by horizontal connections sculpts the distribution of
      activity in this cortical network.

PMID- 12522197
TI  - Recruitment of local inhibitory networks by horizontal connections in layer 2/3
      of ferret visual cortex.
AB  - To investigate how neurons in cortical layer 2/3 integrate horizontal inputs
      arising from widely distributed sites, we combined intracellular recording and
      voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of
      neuronal activity evoked by electrical stimulation of multiple sites in visual
      cortex. Individual stimuli evoked characteristic patterns of optical activity,
      while delivering stimuli at multiple sites generated interacting patterns in the
      regions of overlap. We observed that neurons in overlapping regions received
      convergent horizontal activation that generated nonlinear responses due to the
      emergence of large inhibitory potentials. The results indicate that co-activation
      of multiple sets of horizontal connections recruit strong inhibition from local
      inhibitory networks, causing marked deviations from simple linear integration.

PMID- 12522198
TI  - Differential response properties of IB(4)-positive and -negative unmyelinated
      sensory neurons to protons and capsaicin.
AB  - Activation of unmyelinated (C-fiber) nociceptors by noxious chemicals plays a
      critical role in the initiation and maintenance of injury-induced pain. C-fiber
      nociceptors can be divided into two groups in which one class depends on nerve
      growth factor during postnatal development and contains neuropeptides, and the
      second class depends on glial cell line-derived neurotrophic factor during
      postnatal development and contains few neuropeptides but binds isolectin B(4)
      (IB(4)). We determined the sensitivity of these two populations to protons and
      capsaicin using whole cell recordings of dorsal root ganglion neurons from adult
      mouse. IB(4)-negative unmyelinated neurons were significantly more responsive to
      protons than IB(4)-positive neurons in a concentration-dependent manner.
      Approximately 86% of IB(4)-negative neurons responded to pH 5.0 with an inward
      current compared with only 33% of IB(4)-positive neurons. The subtypes of proton
      evoked currents in IB(4)-negative unmyelinated neurons were also more diverse.
      Many IB(4)-negative neurons exhibited transient, rapidly inactivating proton
      currents as well as sustained proton currents. In contrast, IB(4)-positive
      neurons never displayed transient proton currents and responded to protons only
      with sustained, slowly inactivating inward currents. The two classes of neurons
      also responded differently to capsaicin. Twice as many naive IB(4)-negative
      unmyelinated neurons responded to 1 microM capsaicin as IB(4)-positive neurons,
      and the capsaicin-evoked currents in IB(4)-negative neurons were approximately
      fourfold larger than those in IB(4)-positive neurons. Interestingly, proton
      exposure altered the capsaicin responsiveness of the two classes of neurons in
      opposite ways. Brief preexposure to protons increased the number of capsaicin
      responsive IB(4)-positive neurons by twofold and increased the capsaicin-evoked
      currents by threefold. Conversely, proton exposure decreased the number of
      capsaicin-responsive IB(4)-negative neurons by 50%. These data suggest that IB(4)
      negative unmyelinated nociceptors are initially the primary responders to both
      protons and capsaicin, but IB(4)-positive nociceptors have a unique capacity to
      be sensitized by protons to capsaicin-receptor agonists.

PMID- 12522199
TI  - Surround modulation measured with functional MRI in the human visual cortex.
AB  - Visual context profoundly influences 1) the responses of mammalian visual neurons
      and 2) the perceptual sensitivity of human observers to localized visual stimuli.
      We present data from functional MRI studies demonstrating contextual modulation
      in the human visual cortex. Subjects viewed a circular grating patch that was
      continuously present. A surround grating was added in an ON-OFF block design to
      reveal its effect on the central region. Stimulus-correlated activation was
      quantified and visualized on a flattened map of the occipital gray matter.
      Modulation was measured in a region of interest activated by the central grating
      alone. The observed effects were predominantly suppressive, consistent with the
      effects typically found in single neurons and perception. Suppression was
      greatest when the surround and center had the same orientation and was reduced or
      absent when it was orthogonal. When spatial phase was manipulated, suppression
      was greatest for in-phase center/surround gratings and much reduced or reversed
      (facilitation) for opposite-phase stimuli. With eccentric stimulus presentation,
      suppression was reduced and facilitation became more common. The findings provide
      a direct demonstration of the existence of powerful and stimulus-specific
      surround effects in human visual cortex.

PMID- 12522200
TI  - Afferent innervation patterns of the saccule in pigeons.
AB  - The innervation patterns of vestibular saccular afferents were quantitatively
      investigated in pigeons using biotinylated dextran amine as a neural tracer and
      three-dimensional computer reconstruction. Type I hair cells were found
      throughout a large portion of the macula, with the highest density observed in
      the striola. Type II hair cells were located throughout the macula, with the
      highest density in the extrastriola. Three classes of afferent innervation
      patterns were observed, including calyx, dimorph, and bouton units, with 137
      afferents being anatomically reconstructed and used for quantitative comparisons.
      Calyx afferents were located primarily in the striola, innervated a number of
      type I hair cells, and had small innervation areas. Most calyx afferent terminal
      fields were oriented parallel to the anterior-posterior axis and the
      morphological polarization reversal line. Dimorph afferents were located
      throughout the macula, contained fewer type I hair cells in a calyceal terminal
      than calyx afferents and had medium sized innervation areas. Bouton afferents
      were restricted to the extrastriola, with multi-branching fibers and large
      innervation areas. Most of the dimorph and bouton afferents had innervation
      fields that were oriented dorso-ventrally but were parallel to the neighboring
      reversal line. The organizational morphology of the saccule was found to be
      distinctly different from that of the avian utricle or lagena otolith organs and
      appears to represent a receptor organ undergoing evolutionary adaptation toward
      sensing linear motion in terrestrial and aerial species.

PMID- 12522201
TI  - Dynamic recording of cell death in the in vitro dorsal vagal nucleus of rats in
      response to metabolic arrest.
AB  - Anoxic/ischemic neuronal death is usually assessed in cell cultures or in vivo
      within a time window of 24 h to several days using the nucleic acid stain
      propidium iodide or histological techniques. Accordingly, there is limited
      information on the time course of such neuronal death. We loaded acute rat brain
      stem slices with propidium iodide for dynamic fluorometric recording of metabolic
      arrest-related cell death in the dorsal vagal nucleus. This model was chosen
      because dorsal vagal neurons show a graded response to metabolic inhibition:
      anoxia and aglycemia cause a sustained hyperpolarization, whereas ischemia
      induces a glutamate-mediated, irreversible depolarization. We found that the
      number of propidium iodide-labeled cells increased from 27% to 43% of total cell
      count within 1-7 h after preparation of slices. Compared with these untreated
      control slices, cyanide-induced anoxia (30 min) or aglycemia (1 h) did not cause
      further cell death, whereas 3-h aglycemia destroyed an additional 13% of cells.
      Ischemia (1 h) due to cyanide plus iodoacetate immediately labeled an additional
      20% of cells, and an additional 48% of cells were destroyed within the following
      3 h of postischemia. Continuous recording of propidium iodide fluorescence showed
      that loss of membrane integrity started within 25 min after onset of the ischemic
      depolarization and the concomitant intracellular Ca(2+) rise. The results show
      that propidium iodide can be used to monitor cell death in acute brain slices.
      Our findings suggest that pronounced cell death occurs within a period of 1-4 h
      after onset of metabolic arrest and is apparently due to necrotic/oncotic
      mechanisms.

PMID- 12522202
TI  - Evidence of a specific spinal pathway for the sense of warmth in humans.
AB  - While research on human sensory processing shows that warm input is conveyed from
      the periphery by specific, unmyelinated primary sensory neurons, its pathways in
      the central nervous system (CNS) remain unclear. To gain physiological
      information on the spinal pathways that convey warmth or nociceptive sensations,
      in 15 healthy subjects, we studied the cerebral evoked responses and reaction
      times in response to laser stimuli selectively exciting Adelta nociceptors or C
      warmth receptors at different levels along the spine. To minimize the conduction
      distance along the primary sensory neuron, we directed CO(2)-laser pulses to the
      skin overlying the vertebral spinous processes. Using brain source analysis of
      the evoked responses with high-resolution electroencephalography and a realistic
      model of the head based on individual magnetic resonance imaging scans, we also
      studied the cortical areas involved in the cerebral processing of warm and
      nociceptive inputs. The activation of C warmth receptors evoked cerebral
      potentials with a main positive component peaking at 470-540 ms, i.e., a latency
      clearly longer than that of the corresponding wave yielded by Adelta nociceptive
      input (290-320 ms). Spinal neurons activated by the warm input had a slower
      conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s).
      Brain source analysis of the cerebral responses evoked by the Adelta input
      yielded a very strong fit for one single generator in the mid portion of the
      cingulate gyrus; the warmth-related responses were best explained by three
      generators, one within the cingulate and two in the right and left opercular
      insular cortices. Our results support the existence of slow-conducting second
      order neurons specific for the sense of warmth.

PMID- 12522203
TI  - Gravity-specific adaptation of the angular vestibuloocular reflex: dependence on
      head orientation with regard to gravity.
AB  - The gain of the vertical angular vestibuloocular reflex (aVOR) was adaptively
      altered by visual-vestibular mismatch during rotation about an interaural axis,
      using steps of velocity in three head orientations: upright, left-side down, and
      right-side down. Gains were decreased by rotating the animal and visual surround
      in the same direction and increased by visual and surround rotation in opposite
      directions. Gains were adapted in one head position (single-state adaptation) or
      decreased with one side down and increased with the other side down (dual-state
      adaptation). Animals were tested in darkness using sinusoidal rotation at 0.5 Hz
      about an interaural axis that was tilted from horizontal to vertical. They were
      also sinusoidally oscillated from 0.5 to 4 Hz about a spatial vertical axis in
      static tilt positions from yaw to pitch. After both single- and dual-state
      adaptation, gain changes were maximal when the monkeys were in the position in
      which the gain had been adapted, and the gain changes progressively declined as
      the head was tilted away from that position. We call this gravity-specific aVOR
      gain adaptation. The spatial distribution of the specific aVOR gain changes could
      be represented by a cosine function that was superimposed on a bias level, which
      we called gravity-independent gain adaptation. Maximal gravity-specific gain
      changes were produced by 2-4 h of adaptation for both single- and dual-state
      adaptations, and changes in gain were similar at all test frequencies. When
      adapted while upright, the magnitude and distribution of the gravity-specific
      adaptation was comparable to that when animals were adapted in side-down
      positions. Single-state adaptation also produced gain changes that were
      independent of head position re gravity particularly in association with gain
      reduction. There was no bias after dual-state adaptation. With this difference,
      fits to data obtained by altering the gain in separate sessions predicted the
      modulations in gain obtained from dual-state adaptations. These data show that
      the vertical aVOR gain changes dependent on head position with regard to gravity
      are continuous functions of head tilt, whose spatial phase depends on the
      position in which the gain was adapted. From their different characteristics, it
      is likely that gravity-specific and gravity-independent adaptive changes in gain
      are produced by separate neural processes. These data demonstrate that head
      orientation to gravity plays an important role in both orienting and tuning the
      gain of the vertical aVOR.

PMID- 12522204
TI  - Involvement of the dorsolateral prefrontal cortex of monkeys in visuospatial
      target selection.
AB  - To examine the involvement of the dorsolateral prefrontal cortex (PFC) in
      visuospatial target selection, we induced local, reversible inactivation with
      muscimol at various sites in the dorsolateral PFC of two rhesus monkeys while
      they performed oculomotor visual search (OVS) and oculomotor detection (OD)
      tasks. The OVS task required the subject to select a target stimulus from among
      distractors and to make a saccade to the target location (target selection was
      required for correct performance), whereas the OD task only required a saccade to
      the target (target selection was not required for correct performance). The local
      injection of muscimol (5 microg, 1 microl) into the dorsolateral PFC induced a
      specific deficit in the OVS task but not in the OD task. The deficit in the OVS
      task was characterized by the disordering of saccades for some (mostly a few)
      particular target locations as well as by prolongation of the time required for
      the visual search in most cases. The target locations affected by muscimol were
      biased to the contralateral visual field. Further, the OVS task with "pop-out"
      and "non-pop-out" conditions was similarly impaired by muscimol injection. These
      results suggest that the dorsolateral PFC plays a role in target selection in
      visual space to guide goal-directed motor acts and particular sites are involved
      in target selection for a particular visuospatial coordinate. Further, this
      function of the dorsolateral PFC appears to involve both top-down (active) and
      bottom-up (passive) target-selection/selective attention processes to control
      interfering information (distractors).

PMID- 12522205
TI  - Optical analysis of depolarization waves in the embryonic brain: a dual network
      of gap junctions and chemical synapses.
AB  - Correlated neuronal activity plays a fundamental role in the development of the
      CNS. Using a multiple-site optical recording technique with a voltage-sensitive
      dye, we previously described a novel type of depolarization wave that was evoked
      by cranial or spinal nerve stimulation and spread widely over the whole brain
      region in the chick embryo. We have now investigated developmental expression and
      neuronal network mechanisms of this depolarization wave by applying direct
      stimulation to the brain stem or upper cervical cord of E5-E11 embryos, which
      elicited wave activity similar to that evoked by nerve stimulation. Spatial
      distribution patterns of the depolarization wave changed dynamically with
      development, and this change appeared to be related to the regional differences
      in neuronal differentiation. The depolarization wave was completely eliminated by
      application of either gap junction blockers or an N-methyl-D-aspartate (NMDA)
      receptor antagonist, indicating that functions of both gap junctions and NMDA
      receptors are indispensable for wave propagation. A possible interpretation of
      the results is that dual networks of gap junctions and chemical synaptic coupling
      mediate large-scale depolarization waves in the developing chick CNS.

PMID- 12522206
TI  - Persistent sodium and calcium currents in rat hypoglossal motoneurons.
AB  - Voltage-dependent persistent inward currents are thought to make an important
      contribution to the input-output properties of alpha-motoneurons, influencing
      both the transfer of synaptic current to the soma and the effects of that current
      on repetitive discharge. Recent studies have paid particular attention to the
      contribution of L-type calcium channels, which are thought to be widely
      distributed on both the somatic and the dendritic membrane. However, the relative
      contribution of different channel subtypes as well as their somatodendritic
      distribution may vary among motoneurons of different species, developmental
      stages, and motoneuron pools. In this study, we have characterized persistent
      inward currents in juvenile (10- to 24-day-old) rat hypoglossal (HG) motoneurons.
      Whole-cell, voltage-clamp recordings were made from the somata of visualized rat
      HG motoneurons in 300-microm brain stem slices. Slow (10 s), triangular voltage
      clamp commands from a holding potential of -70 to 0 mV and back elicited whole
      cell currents that were dominated by outward, potassium currents, but often
      showed a region of negative slope resistance on the rising phase of the command.
      In the presence of potassium channel blockers (internal cesium and external 4
      aminopyridine and tetraethylammonium), net inward currents were present on both
      the rising and falling phases of the voltage-clamp command. A portion of the
      inward current present on the ascending phase of the command was mediated by TTX
      sensitive sodium channels, whereas calcium channels mediated the remainder of the
      current. We found roughly the same relative contributions of P-, N-, and L-type
      channels to the calcium currents recorded at the soma that had previously been
      found in neonatal rat HG motoneurons. In most cells, the somatic voltage
      thresholds for calcium current onset and offset were similar and the peak current
      was largest on the ascending phase of the clamp command. However, about one-third
      of the cells exhibited a substantial clockwise current hysteresis, i.e., inward
      currents were present at lower voltages on the descending phase of the clamp
      command. In the same cells, 1-s depolarizing voltage-clamp commands were followed
      by prolonged tail currents, consistent with a prominent contribution from
      dendritic channels. In contrast to previous reports on turtle and mouse
      motoneurons, blocking L-type calcium channels did not eliminate these presumed
      dendritic currents.

PMID- 12522207
TI  - Effect of chronic stress on synaptic currents in rat hippocampal dentate gyrus
      neurons.
AB  - We investigated the effect of chronic stress on synaptic responses of rat dentate
      granule cells to perforant path stimulation. Rats were subjected for 3 wk to
      unpredictable stressors twice daily or to control handling. One day after the
      last stressor, hippocampal slices were prepared and synaptic responses were
      determined with whole-cell recording. At that time, adrenal weight was found to
      be increased and thymus weight as well as gain in body weight were decreased in
      the stressed versus control animals, indicative of corticosterone hypersecretion
      during the stress period. In slices from rats with basal corticosteroid levels
      (at the circadian trough, under rest), no effect of prior stress exposure was
      observed on synaptic responses. However, synaptic responses of dentate granule
      cells from chronically stressed and control rats were differently affected by in
      vitro activation of glucocorticoid receptors, i.e., 1-4 h after administration of
      100 nM corticosterone for 20 min. Thus the maximal response to synaptic
      activation of dentate cells at holding potential of -70 mV [when N-methyl-D
      aspartate (NMDA) receptors are blocked by magnesium] was significantly enhanced
      after corticosterone administration in chronically stressed but not in control
      animals. In accordance, the amplitude of alpha-amino-3-hydroxy-5-methylisolazole
      4-propionic acid (AMPA) but not of NMDA receptor-mediated currents was increased
      by corticosterone in stressed rats, over the entire voltage range. Corticosterone
      treatment also decreased the time to peak of AMPA currents, but this effect did
      not depend on prior stress exposure. The data indicate that following chronic
      stress exposure synaptic excitation of dentate granule cells may be enhanced when
      corticosterone levels rise. This enhanced synaptic flow could contribute to
      enhanced excitation of projection areas of the dentate gyrus, most notably the
      CA3 hippocampal region.

PMID- 12522208
TI  - An unfolded map of the cerebellar dentate nucleus and its projections to the
      cerebral cortex.
AB  - We have used retrograde transneuronal transport of neurotropic viruses to examine
      the organization of the projections from the dentate nucleus of the cerebellum to
      "motor" and "nonmotor" areas of the cerebral cortex. To perform this analysis we
      created an unfolded map of the dentate. Plotting the results from current and
      prior experiments on this unfolded map revealed important features about the
      topography of function in the dentate. We found that the projections to the
      primary motor and premotor areas of the cerebral cortex originated from dorsal
      portions of the dentate. In contrast, projections to prefrontal and posterior
      parietal areas of cortex originated from ventral portions of the dentate. Thus
      the dentate contains anatomically separate and functionally distinct motor and
      nonmotor domains.

PMID- 12522209
TI  - On the persistent sodium current in squid giant axons.
AB  - R. F. Rakowski, D. C. Gadsby, and P. DeWeer have reported a persistent,
      tetrodotoxin-sensitive sodium ion current (I(NaP)) in squid giant axons having a
      low threshold (-90 mV) and a maximal inward amplitude of -4 microA/cm(2) at -50
      mV. This report makes the case that most of I(NaP) is attributable to an ion
      channel mechanism distinct from the classical rapidly activating and inactivating
      sodium ion current, I(Na), which is also tetrodotoxin sensitive. The analysis of
      the contribution of I(Na) to I(NaP) is critically dependent on slow inactivation
      of I(Na). The results of this gating process reported here demonstrate that
      inactivation of I(Na) is complete in the steady-state for V > -40 mV, thereby
      making it unlikely that I(NaP) in this potential range is attributable to I(Na).
      Moreover, -90 mV is well below I(Na) threshold, as demonstrated by the C. A.
      Vandenberg and F. Bezanilla model of I(Na) gating in squid giant axons. Their
      model predicts a persistent current having a threshold of -60 mV and a peak
      amplitude of -25 microA/cm(2) at -20 mV. Modulation of this component by the slow
      inactivation process predicts a persistent current that is finite in the -60- to 
      40-mV range having a peak amplitude of -1 microA/cm(-2) at -50 mV. Subtraction of
      this current from the I(NaP) measurements yields the portion of I(NaP) that
      appears to be attributable to an ion channel mechanism distinct from I(Na).

PMID- 12522210
TI  - Identification of a lactoferrin-derived peptide possessing binding activity to
      hepatitis C virus E2 envelope protein.
AB  - Bovine and human lactoferrins (LF) prevent hepatitis C virus (HCV) infection in
      cultured human hepatocytes; the preventive mechanism is thought to be the direct
      interaction between LF and HCV. To clarify this hypothesis, we have characterized
      the binding activity of LF to HCV E2 envelope protein and have endeavored to
      determine which region(s) of LF are important for this binding activity. Several
      regions of human LF have been expressed and purified as thioredoxin-fused
      proteins in Escherichia coli. Far-Western blot analysis using these LF fragments
      and the E2 protein, expressed in Chinese hamster ovary cells, revealed that the
      93 carboxyl amino acids of LF specifically bound to the E2 protein. The 93
      carboxyl amino acids of LFs derived from bovine and horse cells also possessed
      similar binding activity to the E2 protein. In addition, the amino acid sequences
      of these carboxyl regions appeared to show partial homology to CD81, a candidate
      receptor for HCV, and the binding activity of these carboxyl regions was also
      comparable with that of CD81. Further deletion analysis identified 33 amino acid
      residues as the minimum binding site in the carboxyl region of LF, and the
      binding specificity of these 33 amino acids was also confirmed by using 33
      maltose-binding protein-fused amino acids. Furthermore, we demonstrated that the
      33 maltose-binding protein-fused amino acids prevented HCV infection in cultured
      human hepatocytes. In addition, the site-directed mutagenesis to an Ala residue
      in both terminal residues of the 33 amino acids revealed that Cys at amino acid
      628 was determined to be critical for binding to the E2 protein. These results
      led us to consider the development of an effective anti-HCV peptide. This is the
      first identification of a natural protein-derived peptide that specifically binds
      to HCV E2 protein and prevents HCV infection.

PMID- 12522211
TI  - Identification of a novel protein, PDIP38, that interacts with the p50 subunit of
      DNA polymerase delta and proliferating cell nuclear antigen.
AB  - The yeast two-hybrid screening method was used to identify novel proteins that
      associate with human DNA polymerase delta (pol delta). Two baits were used in
      this study. These were the large (p125) and small (p50) subunits of the core pol
      delta heterodimer. p50 was the only positive isolated with p125 as the bait. Two
      novel protein partners, named PDIP38 and PDIP46, were identified from the p50
      screen. In this study, the interaction of PDIP38 with pol delta was further
      characterized. PDIP38 encodes a protein of 368 amino acids whose C terminus is
      conserved with the bacterial APAG protein and with the F box A protein. It was
      found that PDIP38 also interacts with proliferating cell nuclear antigen (PCNA).
      The ability of PDIP38 to interact with both the p50 subunit of pol delta and with
      PCNA was confirmed by pull-down assays using glutathione S-transferase (GST)
      PDIP38 fusion proteins. The PCNA-PDIP38 interaction was also demonstrated by PCNA
      overlay experiments. The association of PDIP38 with pol delta was shown to occur
      in calf thymus tissue and mammalian cell extracts by GST-PDIP38 pull-down and
      coimmunoprecipitation experiments. PDIP38 was associated with pol delta isolated
      by immunoaffinity chromatography. The association of PDIP38 with pol delta could
      also be demonstrated by native gel electrophoresis.

PMID- 12522212
TI  - Residues Phe342-Asn346 of activated coagulation factor IX contribute to the
      interaction with low density lipoprotein receptor-related protein.
AB  - When blood coagulation factor IX is converted to activated factor IX (factor
      IXa), it develops enzymatic activity and exposes the binding sites for both
      activated factor VIII and the endocytic receptor low density lipoprotein receptor
      related protein (LRP). In the present study we investigated the interaction
      between factor IXa and LRP in more detail, using an affinity-purified soluble
      form of LRP (sLRP). Purified sLRP and full-length LRP displayed similar binding
      to factor IXa. An anti-factor IX monoclonal antibody CLB-FIX 13 inhibited factor
      IXa.sLRP complex formation. Both the antibody and a soluble recombinant fragment
      of LRP (i.e. cluster IV) interfered with factor IXa amidolytic activity,
      suggesting that the antibody and LRP share similar binding regions near the
      active site of factor IXa. Next, a panel of recombinant factor IXa variants with
      amino acid replacements in the surface loops bordering the active site was tested
      for binding to antibody CLB-FIX 13 and sLRP in a solid phase binding assay.
      Factor IXa variants with mutations in the region Phe(342)-Asn(346), located
      between the active site of factor IXa and factor VIII binding helix, showed
      reduced binding to both antibody CLB-FIX 13 and sLRP. Surface plasmon resonance
      analysis revealed that the variant with Asn(346) replaced by Asp displayed slower
      association to sLRP, whereas the variant with residues Phe(342)-Tyr(345) replaced
      by the corresponding residues of thrombin showed faster dissociation. Recombinant
      soluble LRP fragment cluster IV inhibited factor IXa-mediated activation of
      factor X with IC(50) values of 5 and 40 nm in the presence and absence of factor
      VIII, respectively. This inhibition thus seems to occur via two mechanisms: by
      interference with factor IXa.factor VIIIa complex assembly and by direct
      inhibition of factor IXa enzymatic activity. Accordingly, we propose that LRP may
      function as a regulator of blood coagulation.

PMID- 12522213
TI  - Crystal structure of triosephosphate isomerase complexed with 2-phosphoglycolate
      at 0.83-A resolution.
AB  - The atomic resolution structure of Leishmania mexicana triosephosphate isomerase
      complexed with 2-phosphoglycolate shows that this transition state analogue is
      bound in two conformations. Also for the side chain of the catalytic glutamate,
      Glu(167), two conformations are observed. In both conformations, a very short
      hydrogen bond exists between the carboxylate group of the ligand and the
      catalytic glutamate. The distance between O11 of PGA and Oepsilon2 of Glu(167) is
      2.61 and 2.55 A for the major and minor conformations, respectively. In either
      conformation, Oepsilon1 of Glu(167) is hydrogen-bonded to a water network
      connecting the side chain with bulk solvent. This network also occurs in two
      mutually exclusive arrangements. Despite the structural disorder in the active
      site, the C termini of the beta strands that construct the active site display
      the least anisotropy compared with the rest of the protein. The loops following
      these beta strands display various degrees of anisotropy, with the tip of the
      dimer interface loop 3 having very low anisotropy and the C-terminal region of
      the active site loop 6 having the highest anisotropy. The pyrrolidine ring of
      Pro(168) at the N-terminal region of loop 6 is in a strained planar conformation
      to facilitate loop opening and product release.

PMID- 12522214
TI  - Presence of 18-A long hydrogen bond track in the active site of Escherichia coli
      DNA polymerase I (Klenow fragment). Its requirement in the stabilization of
      enzyme-template-primer complex.
AB  - The analysis of the active site region in the crystal structures of template
      primer-bound KlenTaq (Klenow fragment equivalent of Thermus aquaticus polymerase
      I) shows the presence of an approximately 18-A long H-bonding track contributed
      by the Klenow fragment equivalent of Asn(845), Gln(849), Arg(668), His(881), and
      Gln(677). Its location is nearly diagonal to the helical axis of the template
      primer. Four base pairs in the double stranded region proximal to 3' OH end of
      the primer terminus appear to interact with individual amino acid components of
      the track through either the bases or sugar moieties. To understand the
      functional significance of this H-bonding network in the catalytic function of
      Klenow fragment (KF), we generated N845A, N845Q, Q849A, Q849N, R668A, H881A,
      H881V, Q677A, and Q677N mutant species by site-directed mutagenesis. All of the
      mutant enzymes showed low catalytic activity. The kinetic analysis of mutant
      enzymes indicated that K(m)(.dNTP) was not significantly altered, but K(D)(.DNA)
      was significantly increased. Thus the mutant enzymes of the H-bonding track
      residues had decreased affinity for template-primer, although the extent of
      decrease was variable. Most interestingly, even the reduced binding of TP by the
      mutant enzymes occurs in the nonproductive mode. These results demonstrate that
      an H-bonding track is necessary for the binding of template-primer in the
      catalytically competent orientation in the pol I family of enzymes. The
      examination of the interactive environment of individual residues of this track
      further clarifies the mode of cooperation in various functional domains of pol I.

PMID- 12522215
TI  - Xenopus laevis ovarian CYP17 is a highly potent enzyme expressed exclusively in
      oocytes. Evidence that oocytes play a critical role in Xenopus ovarian androgen
      production.
AB  - Progesterone has long been considered the primary mediator of Xenopus oocyte
      maturation. We have recently shown, however, that androgens, which are equal or
      more potent promoters of maturation and are present at higher levels in ovulating
      frogs, may also be playing an important physiologic role in mediating maturation.
      Here, we examined the role of CYP17, a key enzyme mediating sex steroid
      synthesis, in Xenopus ovarian androgen production. We found that the 17,20-lyase
      activities of Xenopus CYP17 exceeded the 17alpha-hydroxylase activities in both
      the Delta4 and Delta5 pathways; thus, Xenopus CYP17 rapidly converted
      pregnenolone and progesterone to dehydroepiandrosterone (DHEA) and
      androstenedione, respectively. This remarkably robust activity exceeds that of
      CYP17 from most higher vertebrates, and likely explains why virtually no
      progesterone is detected in ovulating frogs. Additionally, ovarian CYP17 activity
      was present exclusively in oocytes, although all other enzymes involved in sex
      steroid production were expressed almost entirely in surrounding follicular
      cells. This compartmentalization suggests a "two-cell" model whereby Xenopus
      ovarian androgen production requires both follicular cells and oocytes
      themselves. The requirement of oocytes for ovarian androgen production further
      introduces the unusual paradigm whereby germ cells may be responsible for
      producing important steroids used to mediate their own maturation.

PMID- 12522216
TI  - Ca2+ selectivity and fatty acid specificity of the noncapacitative, arachidonate
      regulated Ca2+ (ARC) channels.
AB  - The arachidonate-regulated, Ca(2+)-selective ARC channels represent a novel
      receptor-activated pathway for the entry of Ca(2+) in nonexcitable cells that is
      entirely separate from the widely studied store-operated, Ca(2+) release
      activated Ca(2+) channels. Activation of ARC channels occurs specifically at the
      low agonist concentrations typically associated with oscillatory Ca(2+) signals
      and appears to provide the predominant mode of Ca(2+) entry under these
      conditions (Mignen, O., Thompson, J. L., and Shuttleworth, T. J. (2001) J. Biol.
      Chem. 276, 35676-35683). In this study we demonstrate that ARC channels are
      present in a variety of different cell types including both cell lines and
      primary cells. Examination of their pharmacology revealed that currents through
      these channels are significantly inhibited by low concentrations (< 5 microm) of
      Gd(3+), are unaffected by 100 microm 2-aminoethyoxydiphenyl borane, and are not
      activated by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (100
      microm). Their selectivity for Ca(2+) was assessed by determining the EC(50) for
      external Ca(2+) block of the monovalent currents observed in the absence of
      external divalent cations. The value obtained (150 nm) indicates that the Ca(2+)
      selectivity of ARC channels is extremely high. Examination of the ability of
      various fatty acids, including arachidonic acid, to activate the ARC channels
      demonstrated that activation does not reflect any nonspecific membrane fluidity
      or detergent effects, shows a high degree of specificity for arachidonic acid
      over other fatty acids (especially monounsaturated and saturated fatty acids),
      and is independent of any arachidonic acid metabolite. Moreover, studies using
      the charged analogue arachidonyl coenzyme A demonstrate that activation of the
      ARC channels reflects an action of the fatty acid specifically at the internal
      face of the plasma membrane. Whether this involves a direct action of arachidonic
      acid on the channel protein itself or an action on some intermediary molecule is,
      at present, unclear.

PMID- 12522217
TI  - Thr-431 and Arg-433 are part of a conserved sequence motif of the glutamine
      amidotransferase domain of CTP synthases and are involved in GTP activation of
      the Lactococcus lactis enzyme.
AB  - A conserved sequence motif within the class 1 glutamine amidotransferase (GATase)
      domain of CTP synthases was identified. The sequence motif in the Lactococcus
      lactis enzyme is (429)GGTLRLG(435). This motif was present only in CTP synthases
      and not in other enzymes that harbor the GATase domain. Therefore, it was
      speculated that this sequence was involved in GTP activation of CTP synthase.
      Other members of the GATase protein family are not activated allosterically by
      GTP. Residues Thr-431 and Arg-433 were changed by site directed mutagenesis to
      the sterically similar residues valine and methionine, respectively. The
      resulting enzymes, T431V and R433M, had both lost the ability for GTP to activate
      the uncoupled glutaminase activity and showed reduced GTP activation of the
      glutamine-dependent CTP synthesis reaction. The T431V enzyme had a similar
      activation constant, K(A), for GTP, but the activation was only 2-3-fold compared
      with 35-fold for the wild type enzyme. The R433M enzyme was found to have a 10-15
      fold lower K(A) for GTP and a concomitant decrease in V(app). The activation by
      GTP of this enzyme was about 7-fold. The kinetic parameters for saturation with
      ATP, UTP, and NH(4)Cl were similar for wild type and mutant enzymes, except that
      the R433M enzyme only had half the V(app) of the wild type enzyme when NH(4)Cl
      was the amino donor. The mutant enzymes T431V and R433M apparently had not lost
      the ability to bind GTP, but the signal transmitted through the enzyme to the
      active sites upon binding of the allosteric effector was clearly disrupted in the
      mutant enzymes.

PMID- 12522218
TI  - Rebalancing teaching and research.

PMID- 12522219
TI  - Space science. Human flight is next step for China's space program.

PMID- 12522220
TI  - Research funding. Expert panel urges a boost for Smithsonian science.

PMID- 12522221
TI  - Bioterrorism. New look at old data irks smallpox-eradication experts.

PMID- 12522222
TI  - Astronomy. Surveys spot ring around the Milky Way.

PMID- 12522223
TI  - Paleoclimate. Tropical Pacific a key to deglaciation.

PMID- 12522224
TI  - National laboratories. UC ties at stake in Los Alamos shakeup.

PMID- 12522225
TI  - Physics. Relativity goes where Einstein sneered to tread.

PMID- 12522227
TI  - Research policy. A new road for Indian science.

PMID- 12522226
TI  - National Institutes of Health. Clinical recruitment stumbles on a logo.

PMID- 12522228
TI  - Asian medicine. The new face of traditional Chinese medicine.

PMID- 12522229
TI  - New perspectives for prion therapeutics meeting. Prion disease treatment's early
      promise unravels.

PMID- 12522230
TI  - International Society for Intelligence research meeting. The practical benefits
      of general intelligence.

PMID- 12522231
TI  - Biomedical policy. Shrugging off doubters, NIH launches a new institute.

PMID- 12522232
TI  - Deep-sea science. Cool corals become hot topic.

PMID- 12522233
TI  - Comment on "Otolith delta18O record of mid-Holocene sea surface temperatures in
      Peru".

PMID- 12522235
TI  - Public health. Toward evidence-based health claims for foods.

PMID- 12522237
TI  - Applied physics. Moore's law forever?

PMID- 12522236
TI  - Development. Lymphatics make the break.

PMID- 12522238
TI  - Circadian rhythms. Circadian photoreception.

PMID- 12522240
TI  - Climate change. Whither Arctic climate?

PMID- 12522239
TI  - Apoptosis. Life and death decisions.

PMID- 12522241
TI  - From anchovies to sardines and back: multidecadal change in the Pacific Ocean.
AB  - In the Pacific Ocean, air and ocean temperatures, atmospheric carbon dioxide,
      landings of anchovies and sardines, and the productivity of coastal and open
      ocean ecosystems have varied over periods of about 50 years. In the mid-1970s,
      the Pacific changed from a cool "anchovy regime" to a warm "sardine regime." A
      shift back to an anchovy regime occurred in the middle to late 1990s. These large
      scale, naturally occurring variations must be taken into account when considering
      human-induced climate change and the management of ocean living resources.

PMID- 12522242
TI  - Reduced pupillary light responses in mice lacking cryptochromes.

PMID- 12522243
TI  - Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory
      pathway.
AB  - A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was
      identified by high-throughput screening as an activator of caspase-3 in extracts
      of a panel of cancer cells. PETCM was used in combination with biochemical
      fractionation to identify a pathway that regulates mitochondria-initiated caspase
      activation. This pathway consists of tumor suppressor putative HLA-DR-associated
      proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins promoted
      caspase-9 activation after apoptosome formation, whereas ProT negatively
      regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved
      ProT inhibition and allowed apoptosome formation at a physiological concentration
      of deoxyadenosine triphosphate. Elimination of ProT expression by RNA
      interference sensitized cells to ultraviolet irradiation-induced apoptosis and
      negated the requirement of PETCM for caspase activation. Thus, this chemical
      biological combinatory approach has revealed the regulatory roles of oncoprotein
      ProT and tumor suppressor PHAP in apoptosis.

PMID- 12522244
TI  - Nanoparticle assembly and transport at liquid-liquid interfaces.
AB  - The self-assembly of particles at fluid interfaces, driven by the reduction in
      interfacial energy, is well established. However, for nanoscopic particles,
      thermal fluctuations compete with interfacial energy and give rise to a particle
      size-dependent self-assembly. Ligand-stabilized nanoparticles assembled into
      three-dimensional constructs at fluid-fluid interfaces, where the properties
      unique to the nanoparticles were preserved. The small size of the nanoparticles
      led to a weak confinement of the nanoparticles at the fluid interface that opens
      avenues to size-selective particle assembly, two-dimensional phase behavior, and
      functionalization. Fluid interfaces afford a rapid approach to equilibrium and
      easy access to nanoparticles for subsequent modification. A photoinduced
      transformation is described in which nanoparticles, initially soluble only in
      toluene, were transported across an interface into water and were dispersed in
      the water phase. The characteristic fluorescence emission of the nanoparticles
      provided a direct probe of their spatial distribution.

PMID- 12522245
TI  - Quantum phase transition in organic charge-transfer complexes.
AB  - A phase transition in an organic charge-transfer complex, which originates from
      the neutral-ionic valence instability, can be tuned toward zero kelvin with use
      of external pressure or chemical modification as a control parameter. The phase
      diagram and observed dielectric behaviors are typical of quantum paraelectricity,
      yet this zero-kelvin transition point namely, the quantum critical point,
      accompanies large quantum fluctuation of the molecular charge, as demonstrated by
      the molecular vibrational mode spectra. The result indicates that the pi-electron
      transfer between donor and acceptor molecules is coupled with the zero-point
      lattice dynamics around the quantum critical point.

PMID- 12522246
TI  - Anthropogenic CO2 uptake by the ocean based on the global chlorofluorocarbon data
      set.
AB  - We estimated the oceanic inventory of anthropogenic carbon dioxide (CO2) from
      1980 to 1999 using a technique based on the global chlorofluorocarbon data set.
      Our analysis suggests that the ocean stored 14.8 petagrams of anthropogenic
      carbon from mid-1980 to mid-1989 and 17.9 petagrams of carbon from mid-1990 to
      mid-1999, indicating an oceanwide net uptake of 1.6 and 2.0 +/- 0.4 petagrams of
      carbon per year, respectively. Our results provide an upper limit on the
      solubility-driven anthropogenic CO2 flux into the ocean, and they suggest that
      most ocean general circulation models are overestimating oceanic anthropogenic
      CO2 uptake over the past two decades.

PMID- 12522247
TI  - Satellite observations of magnetic fields due to ocean tidal flow.
AB  - The ocean is an electrically conducting fluid that generates secondary magnetic
      fields as it flows through Earth's main magnetic field. Extracting ocean flow
      signals from remote observations has become possible with the current generation
      of satellites measuring Earth's magnetic field. Here, we consider the magnetic
      fields generated by the ocean lunar semidiurnal (M2) tide and demonstrate that
      magnetic fields of oceanic origin can be clearly identified in satellite
      observations.

PMID- 12522248
TI  - Dispersal, environment, and floristic variation of western Amazonian forests.
AB  - The distribution of plant species, the species compositions of different sites,
      and the factors that affect them in tropical rain forests are not well
      understood. The main hypotheses are that species composition is either (i)
      uniform over large areas, (ii) random but spatially autocorrelated because of
      dispersal limitation, or (iii) patchy and environmentally determined. Here we
      test these hypotheses, using a large data set from western Amazonia. The
      uniformity hypothesis gains no support, but the other hypotheses do.
      Environmental determinism explains a larger proportion of the variation in
      floristic differences between sites than does dispersal limitation; together,
      these processes explain 70 to 75% of the variation. Consequently, it is important
      that management planning for conservation and resource use take into account both
      habitat heterogeneity and biogeographic differences.

PMID- 12522249
TI  - Diminished pupillary light reflex at high irradiances in melanopsin-knockout
      mice.
AB  - In the mammalian retina, a small subset of retinal ganglion cells (RGCs) are
      intrinsically photosensitive, express the opsin-like protein melanopsin, and
      project to brain nuclei involved in non-image-forming visual functions such as
      pupillary light reflex and circadian photoentrainment. We report that in mice
      with the melanopsin gene ablated, RGCs retrograde-labeled from the
      suprachiasmatic nuclei were no longer intrinsically photosensitive, although
      their number, morphology, and projections were unchanged. These animals showed a
      pupillary light reflex indistinguishable from that of the wild type at low
      irradiances, but at high irradiances the reflex was incomplete, a pattern that
      suggests that the melanopsin-associated system and the classical rod/cone system
      are complementary in function.

PMID- 12522250
TI  - Regulation of blood and lymphatic vascular separation by signaling proteins SLP
      76 and Syk.
AB  - Lymphatic vessels develop from specialized endothelial cells in preexisting blood
      vessels, but the molecular signals that regulate this separation are unknown.
      Here we identify a failure to separate emerging lymphatic vessels from blood
      vessels in mice lacking the hematopoietic signaling protein SLP-76 or Syk. Blood
      lymphatic connections lead to embryonic hemorrhage and arteriovenous shunting.
      Expression of slp-76 could not be detected in endothelial cells, and blood-filled
      lymphatics also arose in wild-type mice reconstituted with SLP-76-deficient bone
      marrow. These studies reveal a hematopoietic signaling pathway required for
      separation of the two major vascular networks in mammals.

PMID- 12522251
TI  - KCNQ1 gain-of-function mutation in familial atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common cardiac arrhythmia whose molecular etiology
      is poorly understood. We studied a family with hereditary persistent AF and
      identified the causative mutation (S140G) in the KCNQ1 (KvLQT1) gene on
      chromosome 11p15.5. The KCNQ1 gene encodes the pore-forming alpha subunit of the
      cardiac I(Ks) channel (KCNQ1/KCNE1), the KCNQ1/KCNE2 and the KCNQ1/KCNE3
      potassium channels. Functional analysis of the S140G mutant revealed a gain-of
      function effect on the KCNQ1/KCNE1 and the KCNQ1/KCNE2 currents, which contrasts
      with the dominant negative or loss-of-function effects of the KCNQ1 mutations
      previously identified in patients with long QT syndrome. Thus, the S140G mutation
      is likely to initiate and maintain AF by reducing action potential duration and
      effective refractory period in atrial myocytes.

PMID- 12522252
TI  - Ringlike structure of the Deinococcus radiodurans genome: a key to
      radioresistance?
AB  - The bacterium Deinococcus radiodurans survives ionizing irradiation and other DNA
      damaging assaults at doses that are lethal to all other organisms. How D.
      radiodurans accurately reconstructs its genome from hundreds of radiation
      generated fragments in the absence of an intact template is unknown. Here we show
      that the D. radiodurans genome assumes an unusual toroidal morphology that may
      contribute to its radioresistance. We propose that, because of restricted
      diffusion within the tightly packed and laterally ordered DNA toroids, radiation
      generated free DNA ends are held together, which may facilitate template
      independent yet error-free joining of DNA breaks.

PMID- 12522253
TI  - Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA
      modification.
AB  - Mutations in DKC1 cause dyskeratosis congenita (DC), a disease characterized by
      premature aging and increased tumor susceptibility. The DKC1 protein binds to the
      box H + ACA small nucleolar RNAs and the RNA component of telomerase. Here we
      show that hypomorphic Dkc1 mutant (Dkc1m) mice recapitulate in the first and
      second generations (G1 and G2) the clinical features of DC. Dkc1m cells from G1
      and G2 mice were impaired in ribosomal RNA pseudouridylation before the onset of
      disease. Reductions of telomere length in Dkc1m mice became evident only in later
      generations. These results suggest that deregulated ribosome function is
      important in the initiation of DC, whereas telomere shortening may modify and/or
      exacerbate DC.

PMID- 12522254
TI  - Role of a highly conserved bacterial protein in outer membrane protein assembly.
AB  - After transport across the cytoplasmic membrane, bacterial outer membrane
      proteins are assembled into the outer membrane. Meningococcal Omp85 is a highly
      conserved protein in Gram-negative bacteria, and its homolog Toc75 is a component
      of the chloroplast protein-import machinery. Omp85 appeared to be essential for
      viability, and unassembled forms of various outer membrane proteins accumulated
      upon Omp85 depletion. Immunofluorescence microscopy revealed decreased surface
      exposure of outer membrane proteins, which was particularly apparent at the cell
      division planes. Thus, Omp85 is likely to play a role in outer membrane protein
      assembly.

PMID- 12522255
TI  - Drosophila BLM in double-strand break repair by synthesis-dependent strand
      annealing.
AB  - Bloom syndrome, characterized by a predisposition to cancer, is caused by
      mutation of the RecQ DNA helicase gene BLM. The precise function of BLM remains
      unclear. Previous research suggested that Drosophila BLM functions in the repair
      of DNA double-strand breaks. Most double-strand breaks in flies are repaired by
      homologous recombination through the synthesis-dependent strand-annealing
      pathway. Here, we demonstrate that Drosophila BLM mutants are severely impaired
      in their ability to carry out repair DNA synthesis during synthesis-dependent
      strand annealing. Consequently, repair in the mutants is completed by error-prone
      pathways that create large deletions. These results suggest a model in which BLM
      maintains genomic stability by promoting efficient repair DNA synthesis and
      thereby prevents double-strand break repair by less precise pathways.

PMID- 12522256
TI  - Control of regulatory T cell development by the transcription factor Foxp3.
AB  - Regulatory T cells engage in the maintenance of immunological self-tolerance by
      actively suppressing self-reactive lymphocytes. Little is known, however, about
      the molecular mechanism of their development. Here we show that Foxp3, which
      encodes a transcription factor that is genetically defective in an autoimmune and
      inflammatory syndrome in humans and mice, is specifically expressed in naturally
      arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3
      converts naive T cells toward a regulatory T cell phenotype similar to that of
      naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene
      for the development of regulatory T cells.

PMID- 12522257
TI  - PDGFRA activating mutations in gastrointestinal stromal tumors.
AB  - Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT
      receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec,
      which inhibits KIT kinase activity. Here we show that approximately 35% (14 of
      40) of GISTs lacking KIT mutations have intragenic activation mutations in the
      related receptor tyrosine kinase, platelet-derived growth factor receptor alpha
      (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable
      with respect to activation of downstream signaling intermediates and cytogenetic
      changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear
      to be alternative and mutually exclusive oncogenic mechanisms in GISTs.

PMID- 12522258
TI  - ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone
      methylation.
AB  - Proteins of the ARGONAUTE family are important in diverse posttranscriptional RNA
      mediated gene-silencing systems as well as in transcriptional gene silencing in
      Drosophila and fission yeast and in programmed DNA elimination in Tetrahymena. We
      cloned ARGONAUTE4 (AGO4) from a screen for mutants that suppress silencing of the
      Arabidopsis SUPERMAN (SUP) gene. The ago4-1 mutant reactivated silent SUP alleles
      and decreased CpNpG and asymmetric DNA methylation as well as histone H3 lysine-9
      methylation. In addition, ago4-1 blocked histone and DNA methylation and the
      accumulation of 25-nucleotide small interfering RNAs (siRNAs) that correspond to
      the retroelement AtSN1. These results suggest that AGO4 and long siRNAs direct
      chromatin modifications, including histone methylation and non-CpG DNA
      methylation.

PMID- 12522259
TI  - Assembly of single chromatin fibers depends on the tension in the DNA molecule:
      magnetic tweezers study.
AB  - We have used magnetic tweezers to study in real time chaperone-mediated chromatin
      assembly/disassembly at the level of single chromatin fibers. We find a strong
      dependence of the rate of assembly on the exerted force, with strong inhibition
      of assembly at forces exceeding 10 pN. During assembly, and especially at higher
      forces, occasional abrupt increases in the length of the fiber were observed,
      giving a clear indication of reversibility of the assembly process. This result
      is a clear demonstration of the dynamic equilibrium between nucleosome assembly
      and disassembly at the single chromatin fiber level.

PMID- 12522260
TI  - Caspase 3 activation is essential for neuroprotection in preconditioning.
AB  - Sublethal insults can induce tolerance to subsequent stressors in neurons. As
      cell death activators such as ROS generation and decreased ATP can initiate
      tolerance, we tested whether other cellular elements normally associated with
      neuronal injury could add to this process. In an in vivo model of ischemic
      tolerance, we were surprised to observe widespread caspase 3 cleavage, without
      cell death, in preconditioned tissue. To dissect the preconditioning pathways
      activating caspases, and the mechanisms by which these proteases are held in
      check, we developed an in vitro model of excitotoxic tolerance. In this model,
      antioxidants and caspase inhibitors blocked ischemia-induced protection against N
      methyl-d-aspartate toxicity. Moreover, agents that blocked preconditioning also
      attenuated induction of HSP 70; transient overexpression of a constitutive form
      of this protein prevented HSP 70 up-regulation and blocked tolerance. We outline
      a neuroprotective pathway where events normally associated with apoptotic cell
      death are critical for cell survival.

PMID- 12522261
TI  - Robustness and the cycle of phosphorylation and dephosphorylation in a two
      component regulatory system.
AB  - The EnvZ/OmpR system in Escherichia coli, which regulates the expression of the
      porins OmpF and OmpC, is one of the simplest and best-characterized examples of
      two-component signaling. Like many other histidine kinases, EnvZ is bifunctional;
      it phosphorylates and dephosphorylates the response regulator OmpR. We have
      analyzed a mathematical model of the EnvZ-mediated cycle of OmpR phosphorylation
      and dephosphorylation. The model predicts that when EnvZ is much less abundant
      than OmpR, as is the case in E. coli, the steady-state level of phosphorylated
      OmpR (OmpR-P) is insensitive to variations in the concentration of EnvZ. The
      model also predicts that the level of OmpR-P is insensitive to variations in the
      concentration of OmpR when the OmpR concentration is sufficiently high. To test
      these predictions, we have perturbed the porin regulatory circuit in E. coli by
      varying the expression levels of EnvZ and OmpR. We have constructed two-color
      fluorescent reporter strains in which ompF and ompC transcription can be easily
      measured in the same culture. Using these strains we have shown that, consistent
      with the predictions of our model, the transcription of ompC and ompF is indeed
      robust or insensitive to a wide range of expression levels of both EnvZ and OmpR.

PMID- 12522262
TI  - Sexual dimorphism in reduced-size liver ischemia and reperfusion injury in mice:
      role of endothelial cell nitric oxide synthase.
AB  - We have recently reported that female mice are protected to a much greater extent
      from the injurious effects of reduced-size liver ischemia and reperfusion
      (RSL+I/R) than are males by an estrogen-dependent mechanism. The objective of
      this study was to examine the possibility that the protective effect observed in
      female mice depends on the up-regulation and/or activation of endothelial cell NO
      synthase (eNOS). Anesthetized female and male wild-type or eNOS-deficient C57BL/6
      mice were subjected to 70% liver ischemia for 45 min followed by resection of the
      remaining 30% nonischemic lobes and reperfusion of ischemic tissue. Survival was
      monitored daily, whereas liver injury was quantified by using serum alanine
      aminotransferase determinations and histopathology. Hepatic eNOS mRNA, protein,
      and enzymatic activity were determined in male and female mice subjected to
      RSL+I/R. We found that liver injury was reduced and survival increased in female
      mice compared with males. This protective effect correlated with significant
      increases in hepatic eNOS message levels and enzyme activity but not protein
      expression compared with males subjected to the surgery. Furthermore, N(omega)
      nitro-L-arginine methyl ester-treated or eNOS-deficient female mice responded to
      RSL+I/R with dramatic increases in liver injury and 100% mortality within 2 days
      of surgery. Finally, we found that pravastatin pretreatment significantly
      attenuated hepatocellular injury and increased survival of male mice, which was
      associated with enhanced expression of eNOS message. We conclude that the
      protective effect afforded female mice is due to the activation of hepatic eNOS
      activity and enhanced NO production.

PMID- 12522263
TI  - Cyclicity of mosquito vitellogenic ecdysteroid-mediated signaling is modulated by
      alternative dimerization of the RXR homologue Ultraspiracle.
AB  - In anautogenous mosquitoes, egg maturation requires a blood meal. As a
      consequence, mosquitoes are vectors of numerous devastating human diseases. Blood
      feeding triggers a 20-hydroxyecdysone (20E) hormonal cascade, which activates
      yolk protein precursor (YPP) genes in the female fat body, an insect metabolic
      tissue. An important adaptation for anautogeny is the previtellogenic arrest
      preventing activation of YPP genes. Equally essential is termination of their
      expression, so that another arrest is achieved after a batch of eggs is laid.
      Here, we report that mosquito Seven-up (AaSvp), a chicken ovalbumin upstream
      promoter-transcription factor homologue, is involved in regulating the cyclicity
      of vitellogenic ecdysteroid-mediated signaling through heterodimerization with a
      retinoid X receptor homologue Ultraspiracle (USP), the obligatory functional
      ecdysteroid receptor (EcR) partner. AaSvp inhibits 20E-dependent activation of
      the vitellogenin (Vg) gene in transfection assays. Two-hybrid and GST pull-down
      analyses demonstrate that in vitro AaSvp interacts with both AaUSP and AaEcR.
      However, the coimmunoprecipitation using fat body nuclear extracts reveals that
      at 33-36 h postblood meal, when the 20E titer sharply declines and YPP gene
      expression ceases, AaSvp replaces AaEcR in USP heterodimers. The chromatin
      immunoprecipitation assay indicates that protein-protein interaction rather than
      binding competition for the Vg ecdysteroid response element accounts for the
      inhibition of Vg expression by AaSvp.

PMID- 12522264
TI  - Autochthonous eukaryotic diversity in hydrothermal sediment and experimental
      microcolonizers at the Mid-Atlantic Ridge.
AB  - The diversity and mode of life of microbial eukaryotes in hydrothermal systems is
      very poorly known. We carried out a molecular survey based on 18S ribosomal RNA
      genes of eukaryotes present in different hydrothermal niches at the Mid-Atlantic
      Ridge. These included metal-rich and rare-earth-element-rich hydrothermal
      sediments of the Rainbow site, fluid-seawater mixing regions, and colonization
      devices (microcolonizers) containing organic, iron-rich, and porous mineral
      substrates that were exposed for 15 days to a fluid source. We identified
      considerable phylogenetic diversity, both at kingdom level and within
      kinetoplastids and alveolates. None of our sequences affiliates to
      photosynthesizing lineages, suggesting that we are targeting only autochthonous
      deep-sea communities. Although sediment harbored most phylogenetic diversity,
      microcolonizers predominantly contained bodonids and ciliates, indicating that
      these protists pioneer the colonization process. Given the large variety of
      divergent lineages detected within the alveolates in deep-sea plankton,
      hydrothermal sediments, and vents, alveolates seem to dominate the deep ocean in
      terms of diversity. Compared with data from the Pacific Guaymas basin, some
      protist lineages seem ubiquitous in hydrothermal areas, whereas others, notably
      kinetoplastid lineages, very abundant and diverse in our samples, so far have
      been detected only in Atlantic systems. Unexpectedly, although alvinellid
      polychaetes are considered endemic of Pacific vents, we detected alvinellid
      related sequences at the fluid-seawater interface and in microcolonizers. This
      finding can boost further studies on deep-sea vent animal biology and
      biogeography.

PMID- 12522265
TI  - Reductive genome evolution in Buchnera aphidicola.
AB  - We have sequenced the genome of the intracellular symbiont Buchnera aphidicola
      from the aphid Baizongia pistacea. This strain diverged 80-150 million years ago
      from the common ancestor of two previously sequenced Buchnera strains. Here, a
      field-collected, nonclonal sample of insects was used as source material for
      laboratory procedures. As a consequence, the genome assembly unveiled
      intrapopulational variation, consisting of approximately 1,200 polymorphic sites.
      Comparison of the 618-kb (kbp) genome with the two other Buchnera genomes
      revealed a nearly perfect gene-order conservation, indicating that the onset of
      genomic stasis coincided closely with establishment of the symbiosis with aphids,
      approximately 200 million years ago. Extensive genome reduction also predates the
      synchronous diversification of Buchnera and its host; but, at a slower rate, gene
      loss continues among the extant lineages. A computational study of protein
      folding predicts that proteins in Buchnera, as well as proteins of other
      intracellular bacteria, are generally characterized by smaller folding efficiency
      compared with proteins of free living bacteria. These and other degenerative
      genomic features are discussed in light of compensatory processes and theoretical
      predictions on the long-term evolutionary fate of symbionts like Buchnera.

PMID- 12522266
TI  - Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers
      inflammatory ischemia in the CNS of transgenic mice.
AB  - Tumor necrosis factor (TNF) is up-regulated in a variety of central nervous
      system (CNS) diseases with diverse etiology and pathologic manifestation. TNF
      mediates multiple biological activities through two membrane receptors, the p55
      and p75 TNF receptors (TNFRs). We have shown previously that human transmembrane
      TNF (tmTNF)p55TNFR signaling in transgenic mice triggers oligodendrocyte
      apoptosis, endothelial cell activation, parenchymal inflammation, and primary
      demyelinating lesions similar to those of acute multiple sclerosis. To address
      the role of the p75TNFR in the CNS, we have generated "humanized" mice that
      express human tmTNF in astrocytes and a physiologically regulated human p75TNFR
      transgene, in the absence of the endogenous (murine) p55TNFR. Human tmTNFp75TNFR
      transgenic mice develop CNS vascular pathology, characterized by endothelial cell
      activation, meningeal inflammation, and vessel fibrosis. There is no evidence of
      oligodendrocyte apoptosis or primary demyelination in these mice. Late in
      disease, vasculitis can result in vessel occlusion and secondary, multifocal CNS
      ischemic injury. These results identify a proinflammatory role for the p75TNFR at
      the level of the CNS vascular endothelium, which correlates with the expression
      pattern of this receptor in the CNS, and indicate that the differential
      expression patterns of the two TNFRs within the CNS play a significant role in
      shaping the outcome of TNF signaling during neuroimmune interactions.

PMID- 12522267
TI  - The binding specificity and affinity determinants of family 1 and family 3
      cellulose binding modules.
AB  - Cellulose binding modules (CBMs) potentiate the action of cellulolytic enzymes on
      insoluble substrates. Numerous studies have established that three aromatic
      residues on a CBM surface are needed for binding onto cellulose crystals and that
      tryptophans contribute to higher binding affinity than tyrosines. However,
      studies addressing the nature of CBM-cellulose interactions have so far failed to
      establish the binding site on cellulose crystals targeted by CBMs. In this study,
      the binding sites of CBMs on Valonia cellulose crystals have been visualized by
      transmission electron microscopy. Fusion of the CBMs with a modified
      staphylococcal protein A (ZZ-domain) allowed direct immuno-gold labeling at close
      proximity of the actual CBM binding site. The transmission electron microscopy
      images provide unequivocal evidence that the fungal family 1 CBMs as well as the
      family 3 CBM from Clostridium thermocellum CipA have defined binding sites on two
      opposite corners of Valonia cellulose crystals. In most samples these corners are
      worn to display significant area of the hydrophobic (110) plane, which thus
      constitutes the binding site for these CBMs.

PMID- 12522268
TI  - CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary
      carcinoma cells to a normal morphogenic phenotype in a 3D culture.
AB  - In a 3D model of breast morphogenesis, CEACAM1 (carcinoembryonic antigen-related
      cell adhesion molecule 1) plays an essential role in lumen formation in a subline
      of the nonmalignant human breast cell line (MCF10A). We show that mammary
      carcinoma cells (MCF7), which do not express CEACAM1 or form lumena when grown in
      Matrigel, are restored to a normal morphogenic program when transfected with
      CEACAM1-4S, the short cytoplasmic isoform of CEACAM1 that predominates in breast
      epithelia. During the time course of lumen formation, CEACAM1-4S was found
      initially between the cells, and in mature acini, it was found exclusively in an
      apical location, identical to its expression pattern in normal breast. Lumena
      were formed by apoptosis as opposed to necrosis of the central cells within the
      alveolar structures, and apoptotic cells within the lumena expressed CEACAM1-4S.
      Dying cells exhibited classical hallmarks of apoptosis, including nuclear
      condensation, membrane blebbing, caspase activation, and DNA laddering. Apoptosis
      was mediated by Bax translocation to the mitochondria and release of cytochrome c
      into the cytoplasm, and was partially inhibited by culturing cells with caspase
      inhibitors. The dynamic changes in CEACAM1 expression during morphogenesis,
      together with studies implicating extracellular matrix and integrin signaling,
      suggest that a morphogenic program integrates cell-cell and cell-extracellular
      matrix signaling to produce the lumena in mammary glands. This report reveals a
      function of CEACAM1-4S relevant to cellular physiology that distinguishes it from
      its related long cytoplasmic domain isoform.

PMID- 12522269
TI  - Chaperones increase association of tau protein with microtubules.
AB  - Molecular chaperones and their functions in protein folding have been implicated
      in several neurodegenerative diseases, including Parkinson's disease and
      Huntington's disease, which are characterized by accumulation of protein
      aggregates (e.g., alpha-synuclein and huntingtin, respectively). These aggregates
      have been shown in various experimental systems to respond to changes in levels
      of molecular chaperones suggesting the possibility of therapeutic intervention
      and a role for chaperones in disease pathogenesis. It remains unclear whether
      chaperones also play a role in Alzheimer's disease, a neurodegenerative disorder
      characterized by beta-amyloid and tau protein aggregates. Here, we report an
      inverse relationship between aggregated tau and the levels of heat shock protein
      (Hsp)7090 in tau transgenic mouse and Alzheimer's disease brains. In various
      cellular models, increased levels of Hsp70 and Hsp90 promote tau solubility and
      tau binding to microtubules, reduce insoluble tau and cause reduced tau
      phosphorylation. Conversely, lowered levels of Hsp70 and Hsp90 result in the
      opposite effects. We have also demonstrated a direct association of the
      chaperones with tau proteins. Our results suggest that up-regulation of molecular
      chaperones may suppress formation of neurofibrillary tangles by partitioning tau
      into a productive folding pathway and thereby preventing tau aggregation.

PMID- 12522272
TI  - Effect of vitamin A supplementation on childhood morbidity and mortality:
      critical review of Indian studies.
AB  - OBJECTIVE: To review all published randomized trials concerned with linkage of
      vitamin A supplementation with reduction of mortality and morbidity in Indian
      children. METHOD: The studies were identified by searching the PubMed, review
      articles, references of available meta-analyses and bibliography of pertinent
      references. Studies were extracted and the quality of each study was reviewed
      with regards to 10 categories of parameters that in our opinion, were important
      for a vitamin A prophylaxis trial. These included background indicators,
      subjects, design, intervention, proximal measures, field-work, sources of bias,
      data analysis, interpretation and documentation. RESULTS: Out of 12 studies
      satisfying the inclusion criteria, the available 11 were examined. Two of the
      trials were concerned with mortality, 6 with morbidity, and 2 with both mortality
      and morbidity; 1 study assessed the impact of vitamin A on pneumococcal
      colonization. Out of 4 mortality trials, only one could satisfactorily report a
      significant reduction (54 percent) in child mortality following vitamin A
      supplementation. Of 8 morbidity studies, only 3 indicated some beneficial effect
      of vitamin A supplementation. None of the studies was perfect in methodology. We
      could not locate any study that addressed the issue of cost-effectiveness or
      dietary modifications. The results were not unequivocal and findings for
      mortality and morbidity were not corroborative. CONCLUSION: There is no definite
      evidence as yet in favor or against substantial benefit of universal vitamin A
      supplementation to children in India. There is a clear need to undertake a
      comprehensive trial with adequate sample size and a standardized methodology that
      could give clear, unbiased, and convincing evidence on the role of routine
      vitamin A supplementation.

PMID- 12522270
TI  - Profiling of tyrosine phosphorylation pathways in human cells using mass
      spectrometry.
AB  - The reversible phosphorylation of tyrosine residues is an important mechanism for
      modulating biological processes such as cellular signaling, differentiation, and
      growth, and if deregulated, can result in various types of cancer. Therefore, an
      understanding of these dynamic cellular processes at the molecular level requires
      the ability to assess changes in the sites of tyrosine phosphorylation across
      numerous proteins simultaneously as well as over time. Here we describe a
      sensitive approach based on multidimensional liquid chromatography/mass
      spectrometry that enables the rapid identification of numerous sites of tyrosine
      phosphorylation on a number of different proteins from human whole cell lysates.
      We used this methodology to follow changes in tyrosine phosphorylation patterns
      that occur over time during either the activation of human T cells or the
      inhibition of the oncogenic BCR-ABL fusion product in chronic myelogenous
      leukemia cells in response to treatment with STI571 (Gleevec). Together, these
      experiments rapidly identified 64 unique sites of tyrosine phosphorylation on 32
      different proteins. Half of these sites have been documented in the literature,
      validating the merits of our approach, whereas motif analysis suggests that a
      number of the undocumented sites are also potentially involved in biological
      pathways. This methodology should enable the rapid generation of new insights
      into signaling pathways as they occur in states of health and disease.

PMID- 12522273
TI  - Doctors and criminal law.

PMID- 12522274
TI  - Anemia in adolescent girls: a preliminary report from semi-urban Nepal.
AB  - The present study was conducted to determine the prevalence of anemia in
      adolescent Nepalese girls in a semi urban setting. A total of 209 apparently
      healthy girls between the ages of 11-18 years were recruited and information
      collected on menarcheal status and socio-demographic profile. All girls were
      subjected to anthropometric examination and hematocrit estimation. Anemia was
      defined as hematocrit less than 36, as per WHO cut-off. The overall prevalence of
      anemia was found to be 68.8%. This prevalence was not related to girls' age, body
      mass index, menarcheal status, and socio-demographic factors including parental
      education or occupation ( p = 0.05).

PMID- 12522275
TI  - Thoracoscopic thymectomy for juvenile myasthenia gravis.
AB  - Thoracoscopic thymectomy is feasible in adolescents with myasthenia gravis. It
      allows complete resection of the gland with less morbidity, shorter ICU and
      hospital stay and far superior cosmetic result as compared to trans-sternal
      thymectomy. Our experience with this procedure in 9 adolescents with myasthenia
      gravis is presented along with review of the relevant literature.

PMID- 12522276
TI  - Laparoscopy in diagnosis of prolonged neonatal jaundice.
AB  - When managing neonatal jaundice, there is no single test or imaging modality that
      can reliably define biliary atresia and neonatal hepatitis. Early diagnosis is an
      important step for surgical success in extra hepatic biliary atresia. In many
      situations, exploratory laparotomy and operative cholangiography may be needed to
      settle the definitive diagnosis, with the risk of having negative exploration in
      those high risk patients with medical etiology. The use of laparoscopy may help
      in avoiding unnecessary exploration for such group of patients and arriving at a
      definite diagnosis. Six patients with conjugated hyperbilirubinemia were
      evaluated with a diagnostic laparoscopy, laparoscopic cholangiography and liver
      biopsy. Three of the six patients were diagnosed to have neonatal hepatitis and
      so an unnecessary laparotomy was avoided in these cases.

PMID- 12522277
TI  - Clinical outcome and neurological sequelae in serologically confirmed cases of
      Japanese encephalitis patients in Assam, India.
AB  - We report the clinical outcome and prognostic factors in 39 cases of childhood
      Japanese Encephalitis admitted to a tertiary hospital of Upper Assam and followed
      up for 421 days in the community. The mortality rate was 20.5% in our study. The
      mean GCS (9.97 +/- 0.91) was higher in surviving cases than the fatal cases (GCS
      7.5 +/- 1.78) at admission. The fatal cases died within 4.75 +/- 3.19 days in the
      hospital. All the patients had low BMI (surviving cases 13.54 +/- 2.3; fatal
      cases 12.05 +/- 0.12) and were anemic. Cerebrospinal fluid (CSF) was clear in
      91.4% cases but pressure and protein content were increased in all cases. About
      10% cases had parkinsonian features at the time of discharge. Residual symptoms
      remained in about one third of cases even after 421 days.

PMID- 12522278
TI  - Restrictive dermopathy - a case report.

PMID- 12522279
TI  - Relapsing hypertrophic osteoarthropathy in a child with bronchiectasis.

PMID- 12522280
TI  - Acute suppurative thyroiditis with thyroid abscess.

PMID- 12522281
TI  - Congenital contractural arachnodactyly (Beals syndrome): first case report with
      hypospadias.

PMID- 12522282
TI  - Larva migrans eruption in an infant.

PMID- 12522283
TI  - Keratosis pilaris.

PMID- 12522284
TI  - Seckel syndrome.

PMID- 12522285
TI  - Congenital tuberculosis.

PMID- 12522286
TI  - A new Lact-aid technique.

PMID- 12522287
TI  - Nebulized adrenaline vs. salbutamol in wheeze associated respiratory infections.

PMID- 12522289
TI  - Clinical evaluation of acute respiratory distress and chest wheezing in infants:
      a few practical difficulties.

PMID- 12522291
TI  - Contraindictions of Varicella vaccine.

PMID- 12522293
TI  - Structure determination of a pseudotripeptide zinc complex with the COSMOS-NMR
      force field and DFT methods.
AB  - A His-X-His pseudotripeptide zinc complex (X is a N-alkyl glycine derivative)
      similar to the catalytic center of the carbonic anhydrase was computer designed
      and experimentally synthesized. Using 2D-NMR techniques, all proton, carbon
      chemical shifts and nuclear overhauser effect signals were assigned. The three
      dimensional structure of the complex was determined with the COSMOS (computer
      simulation of molecular structures) force field by applying 13C bond polarization
      theory chemical shift pseudo forces and restrictions for NOE distances. From
      molecular dynamics, simulated annealing simulations and geometry optimizations,
      the three best force field structures were taken for a final investigation by
      density functional theory calculations.

PMID- 12522294
TI  - TROSY experiment for refinement of backbone psi and phi by simultaneous
      measurements of cross-correlated relaxation rates and 3,4J(H alpha HN) coupling
      constants.
AB  - The TROSY principle has been introduced into a HNCA experiment, which is designed
      for measurements of the intraresidual and sequential H(alpha)-C(alpha)/H(N)-N
      dipole/dipole and H(alpha)-C(alpha)/N dipole/CSA cross-correlated relaxation
      rates. In addition, the new experiment provides values of the (3,4)J(H alpha HN)
      coupling constants measured in an E.COSY manner. The conformational restraints
      for the psi and phi angles are obtained through the use of the cross-correlated
      relaxation rates together with the Karplus-type dependencies of the coupling
      constants. Improved signal-to-noise is achieved through preservation of all
      coherence transfer pathways and application of the TROSY principle. The
      application of the [(15)N,(13)C]-DQ/ZQ-[(15)N,(1)H]-TROSY-E.COSY experiment to
      the 16 kDa apo-form of the E. coli Heme Chaperon protein CcmE is described.
      Overall good agreement is achieved between psi and phi angles measured with the
      new experiment and the average values determined from an ensemble of 20 NMR
      conformers.

PMID- 12522295
TI  - Backbone dynamics of the cytotoxic ribonuclease alpha-sarcin by 15N NMR
      relaxation methods.
AB  - The cytotoxic ribonuclease alpha-sarcin is a 150-residue protein that inactivates
      ribosomes by selectively cleaving a single phosphodiester bond in a strictly
      conserved rRNA loop. In order to gain insights on the molecular basis of its
      highly specific activity, we have previously determined its solution structure
      and studied its electrostatics properties. Here, we complement those studies by
      analysing the backbone dynamics of alpha-sarcin through measurement of
      longitudinal relaxation rates R1, off resonance rotating frame relaxation rates
      R1 rho, and the 15N[1H] NOE of the backbone amide 15N nuclei at two different
      magnetic field strengths (11.7 and 17.6 T). The two sets of relaxation parameters
      have been analysed in terms of the reduced spectral density mapping formalism, as
      well as by the model-free approach. alpha-Sarcin behaves as an axial symmetric
      rotor of the prolate type (D(axially)/D(radially)=1.16 +/- 0.02) which tumbles
      with a correlation time tau(m) of 7.54 +/- 0.02 ns. The rotational diffusion
      properties have been also independently evaluated by hydrodynamic calculations
      and are in good agreement with the experimental results. The analysis of the
      internal dynamics reveals that alpha-sarcin is composed of a rigid hydrophobic
      core and some exposed segments which undergo fast (ps to ns) internal motions.
      Slower motions in the mu s to ms time scale are less abundant and in some cases
      can be assigned to specific motional processes. All dynamic data are discussed in
      relation to the role of some particular residues of alpha-sarcin in the process
      of recognition of its ribosomal target.

PMID- 12522296
TI  - Residual dipolar coupling constants and structure determination of large DNA
      duplexes.
AB  - Several NMR works have shown that long-range information provided by residual
      dipolar couplings (RDCs) significantly improve the global structure definition of
      RNAs and DNAs. Most of these are based on the use of a large set of RDCs, the
      collect of which requires samples labeled with (13)C, (15)N, and sometimes, (2)H.
      Here, we carried out torsion-angle dynamics simulations on a non-self
      complementary DNA fragment of 17 base-pairs,
      d(GGAAAATATCTAGCAGT).(ACTGCTAGAGATTTTCC). This reproduces the U5 LTR distal end
      of the HIV-1 cDNA that contains the enzyme integrase binding site. Simulations
      aimed at evaluating the impact of RDCs on the structure definition of long
      oligonucleotides, were performed in incorporating (i) nOe-distances at both < 4.5
      A and < 5 A; (ii) a small set of (13)C-(1)H RDCs, easily detectable at the
      natural abundance, and (iii) a larger set of RDCs only accessible through the
      (13)C labeling of DNAs. Agreement between a target structure and a simulated
      structure was measured in terms of precision and accuracy. Results allowed to
      define conditions in which accurate DNA structures can be determined. We
      confirmed the strong impact of RDCs on the structure determination, and, above
      all, we found that a small set of RDC constraints (ca. 50) detectable at the
      natural abundance is sufficient to accurately derive the global and local DNA
      duplex structures when used in conjunction with nOe-distances < 5 A.

PMID- 12522297
TI  - Random coil proton chemical shifts of deoxyribonucleic acids.
AB  - Sixteen 17-nucleotide DNA sequences have been used to determine the sequence
      effect on random coil DNA proton chemical shifts. Based on the proton chemical
      shifts measured for the central nucleotides in 64 triplets and the correction
      factors determined for the next nearest neighbor effects, a parameter set has
      been derived for predicting random coil DNA proton chemical shifts. The root-mean
      square deviation (RMSD) between the predicted and the observed aromatic H6/H8
      proton chemical shifts of approximately 200 data from 22 random coil DNA
      sequences was determined to be 0.02 ppm with a correlation coefficient of 0.998.
      For the H1', H2', H2" and H3' sugar protons, the RMSD values between the
      predicted and the experimental shifts were found to be 0.02, 0.03, 0.03 and 0.02
      ppm, respectively.

PMID- 12522298
TI  - Program MULDER -- a tool for extracting torsion angles from NMR data.
AB  - MULDER (Mostly UniversaL Dihedral angle ExtractoR) is a program for extraction of
      torsion angle information from NMR data. Currently, it can analyze two types of
      input data: The torsion angle data, where several (3)J-coupling constants and/or
      interatomic distances are combined in order to reduce the torsion angle ambiguity
      arising from solving the isolated Karplus (or distance) equation, and the sugar
      pucker data, where the dynamics of five-membered sugar rings is evaluated by
      postprocessing the results calculated from (3)J((HH)) coupling constants by
      program PSEUROT. Program MULDER can be used either as an alternative to r-MD
      programs in situations where only specific structural features are studied, or as
      a preparatory tool in connection with full r-MD structure calculation for
      extraction of unambiguous torsion angle restraints.

PMID- 12522299
TI  - Charged acrylamide copolymer gels as media for weak alignment.
AB  - The use of mechanically strained acrylamide/acrylate copolymers is reported as a
      new alignment medium for biomacromolecules. Compared to uncharged, strained
      polyacrylamide gels, the negative charges of the acrylamide/acrylate copolymer
      strongly alter the alignment tensor and lead to pronounced electroosmotic
      swelling. The swelling itself can be used to achieve anisotropic, mechanical
      strain. The method is demonstrated for the alignment of TipAS, a 17 kDa
      antibiotic resistance protein, as well as for human ubiquitin, where alignment
      tensors with an A(ZZ,NH) of up to 60 Hz are achieved at a gel concentration of 2%
      (w/v). The alignment can be modulated by the variation of pH, ionic strength, and
      gel concentration. The high mechanical stability of the swollen gels makes it
      possible to obtain alignment at polymer concentrations of less than 1% (w/v).

PMID- 12522300
TI  - Backbone 1H, 13C, and 15N resonance assignments of the von Willebrand factor A3
      domain.

PMID- 12522301
TI  - 1H, 15N and 13C assignments of the carboxy-terminal domain of the transmembrane
      electron transfer protein DsbD.

PMID- 12522302
TI  - Backbone NMR assignments of the metal-free UreE from Bacillus pasteurii.

PMID- 12522303
TI  - 1H, 13C and 15N chemical shift assignments of the SH2 domain of the Csk
      homologous kinase.

PMID- 12522304
TI  - Assignment of the 1H, 13C and 15N resonances of the coxsackievirus and adenovirus
      receptor domain 1.

PMID- 12522305
TI  - Backbone 1H, 15N, and 13C resonance assignments of the repeated domain of human
      beta ig-h3 protein.

PMID- 12522306
TI  - Protein NMR structure determination with automated NOE-identification in the
      NOESY spectra using the new software ATNOS.
AB  - Novel algorithms are presented for automated NOESY peak picking and NOE signal
      identification in homonuclear 2D and heteronuclear-resolved 3D [(1)H,(1)H]-NOESY
      spectra during de novo protein structure determination by NMR, which have been
      implemented in the new software ATNOS (automated NOESY peak picking). The input
      for ATNOS consists of the amino acid sequence of the protein, chemical shift
      lists from the sequence-specific resonance assignment, and one or several 2D or
      3D NOESY spectra. In the present implementation, ATNOS performs multiple cycles
      of NOE peak identification in concert with automated NOE assignment with the
      software CANDID and protein structure calculation with the program DYANA. In the
      second and subsequent cycles, the intermediate protein structures are used as an
      additional guide for the interpretation of the NOESY spectra. By incorporating
      the analysis of the raw NMR data into the process of automated de novo protein
      NMR structure determination, ATNOS enables direct feedback between the protein
      structure, the NOE assignments and the experimental NOESY spectra. The main
      elements of the algorithms for NOESY spectral analysis are techniques for local
      baseline correction and evaluation of local noise level amplitudes, automated
      determination of spectrum-specific threshold parameters, the use of symmetry
      relations, and the inclusion of the chemical shift information and the
      intermediate protein structures in the process of distinguishing between NOE
      peaks and artifacts. The ATNOS procedure has been validated with experimental NMR
      data sets of three proteins, for which high-quality NMR structures had previously
      been obtained by interactive interpretation of the NOESY spectra. The ATNOS-based
      structures coincide closely with those obtained with interactive peak picking.
      Overall, we present the algorithms used in this paper as a further important step
      towards objective and efficient de novo protein structure determination by NMR.

PMID- 12522307
TI  - Three-way decomposition of a complete 3D 15N-NOESY-HSQC.
AB  - Three-way decomposition is applied for the structural analysis of a complete
      three-dimensional (15)N-NOESY-HSQC of the 128 residues long protein azurin. The
      procedure presented includes decomposition using the software MUNIN, providing an
      initial characterization of the complete spectrum by 355 components. This is
      followed by post-processing yielding a final list of 149 components, 123 of which
      characterize 1859 NOE peaks from backbone N-H groups. Components from three-way
      decomposition are defined as direct products of one-dimensional shapes along the
      three dimensions. Thus, a complete set of distance constraints from this spectrum
      is obtained by one-dimensional peak picking of the shapes along the NOE
      dimension. Correctness and completeness of this set of NOEs are tested for all
      backbone amide groups against both an independent peak picking algorithm and the
      three-dimensional crystal structure of azurin, and a coincidence of about 95% is
      observed. Automated 'demixing' of components that are 'mixed' in a complex manner
      due to overlap of the HN and/or (15)N frequencies is illustrated.

PMID- 12522308
TI  - Sorting signals from protein NMR spectra: SPI, a Bayesian protocol for uncovering
      spin systems.
AB  - Grouping of spectral peaks into J-connected spin systems is essential in the
      analysis of macromolecular NMR data as it provides the basis for disentangling
      chemical shift degeneracies. It is a mandatory step before resonance and NOESY
      cross-peak identities can be established. We have developed SPI, a computational
      protocol that scrutinizes peak lists from homo- and hetero-nuclear
      multidimensional NMR spectra and progressively assembles sets of resonances into
      consensus J- and/or NOE-connected spin systems. SPI estimates the likelihood of
      nuclear spin resonances appearing at defined frequencies given sets of cross
      peaks measured from multi-dimensional experiments. It quantifies spin system
      matching probabilities via Bayesian inference. The protocol takes advantage of
      redundancies in the number of connectivities revealed by suites of diverse NMR
      experiments, systematically tracking the adequacy of each grouping hypothesis.
      SPI was tested on 2D homonuclear and 2D/3D(15)N-edited data recorded from two
      protein modules, the col 2 domain of matrix metalloproteinase-2 (MMP-2) and the
      kringle 2 domain of plasminogen, of 60 and 83 amino acid residues, respectively.
      For these protein domains SPI identifies approximately 95% unambiguous resonance
      frequencies, a relatively good performance vis-a-vis the reported 'manual'
      (interactive) analyses. Abbreviations and Acronyms: SPI, SPin Identification;
      BMRB, BioMagResBank (Madison, WI).

PMID- 12522309
TI  - Factors determining the reliable description of global tumbling parameters in
      solution NMR.
AB  - An accurate description of global tumbling of a protein is essential for correct
      analysis and interpretation of internal dynamics and thermodynamics. The accurate
      fitting of global tumbling parameters is affected by the number of experimental
      relaxation data points available for analysis, the distribution of data points
      over the domain of the function describing the tumbling, the measurement error
      associated with the data, the error associated with use of an approximate
      functional form, and errors in the protein structure. We present an analysis of
      the influence of these factors on the error in global tumbling parameters and the
      corresponding error in the calculated T(1)/T(2) values. We find that reduction of
      experimental and approximation error can compensate for a less-than-ideal
      quantity or distribution of data points, and that accurate parameters can be
      obtained for proteins with highly anisotropic distributions of bond vectors, as
      illustrated using the helical bundle protein G-CSF. This indicates that proteins
      with anisotropic distributions, such as the helical bundle class of proteins,
      should not summarily be excluded when selecting proteins for dynamic and
      thermodynamic analyses of (15)N backbone relaxation measurements.

PMID- 12522310
TI  - Biosynthetically directed fractional 13C labeling facilitates identification of
      Phe and Tyr aromatic signals in proteins.
AB  - Analysis of 2D [(13)C,(1)H]-HSQC spectra of biosynthetic fractionally (13)C
      labeled proteins is a reliable, straightforward means to obtain stereospecific
      assignments of Val and Leu methyl sites in proteins. Herein we show that the same
      fractionally labeled protein sample facilitates observation and identification of
      Phe and Tyr aromatic signals. This is the case, in part, because the fractional
      (13)C labeling yields aromatic rings in which some of the (13)C-(13)C J
      couplings, present in uniformly labeled samples, are absent. Also, the number of
      homonuclear J-coupling partners differs for the delta-, epsilon- and zeta
      carbons. This enabled us to vary their signal intensities in distinctly different
      ways by appropriately setting the (13)C constant-time period in 2D [(13)C,(1)H]
      HSQC spectra. We illustrate the application of this approach to an 18 kDa
      protein, c-VIAF, a modulator of apoptosis. In addition, we show that cancellation
      of the aromatic (13)C CSA and (13)C-(1)H dipolar interactions can be fruitfully
      utilized in the case of the fractionally labeled sample to obtain high resolution
      (13)C constant-time spectra with good sensitivity.

PMID- 12522311
TI  - Chemical shift correlation via RFDR: elimination of resonance offset effects.
AB  - It is shown that it is possible to effectively execute RFDR experiments with
      adiabatic inversion pulses and obtain resonance offset compensation that is
      superior to what can be achieved by conventional rectangular pulses. Employing 40
      micros tanh/tan adiabatic pulses at a power level of approximately 38 kHz and a
      spinning speed of 12 kHz it is demonstrated that the range of resonance offset
      compensation achieved is sufficient to generate, via a single experiment,
      homonuclear chemical shift correlation spectra in the entire (13)C chemical shift
      range in peptides/proteins at the currently available field strengths.

PMID- 12522313
TI  - Differential multiple quantum relaxation caused by chemical exchange outside the
      fast exchange limit.
AB  - Differential relaxation of multiple quantum coherences is a signature for
      chemical exchange processes in proteins. Previous analyses of experimental data
      have used theoretical descriptions applicable only in the limit of fast exchange.
      Theoretical expressions for differential relaxation rate constants that are
      accurate outside fast exchange are presented for two-spin-system subject to two
      site chemical exchange. The theoretical expressions are validated using
      experimental results for (15)N-(1)H relaxation in basic pancreatic trypsin
      inhibitor. The new theoretical expression is valuable for identification and
      characterization of exchange processes in proteins using differential relaxation
      of multiple quantum coherences.

PMID- 12522312
TI  - Unblocked statistical-coil tetrapeptides and pentapeptides in aqueous solution: a
      theoretical study.
AB  - NMR studies of the molecular conformations of peptides and proteins rely on a
      comparison of the relevant spectral parameters with the corresponding values for
      so-called statistical-coil polypeptides. For this reason, it is necessary to
      characterize the experimental ensemble of states populated by statistical-coil
      peptides. Such a characterization, however, has proven to be both difficult and
      sensitive to changes in many environmental parameters such as solvent
      composition, temperature, pH, as well as the neighboring amino acids in the
      sequence. As a consequence, a series of significant discrepancies has been
      reported for some experimentally observed parameters, such as chemical shifts, or
      vicinal coupling constants, (3)J(NHalpha), whose values appear to be incompatible
      with a statistical-coil ensemble. In this work, we report the results of a
      molecular mechanics study of a series of unblocked tetra- and pentapeptides under
      different pH conditions. These calculations were carried out with explicit
      consideration of both the coupling between the process of proton binding/release
      and conformation adopted by the molecule at a given pH and the contribution of
      the conformational entropy to the total free energy. Good agreement was found
      between the calculated and experimentally determined values of the vicinal
      coupling constant, (3)J(NHalpha), the alpha-proton chemical shift, and the
      (13)C(alpha) chemical shift. All the evidence accumulated in these theoretical
      calculations helps to rationalize some of the unsettled anomalies observed
      experimentally, and to provide an understanding of the effect of pH and amino
      acid sequence on the conformational preferences of statistical-coil peptides.

PMID- 12522314
TI  - 1H, 13C, and 15N backbone resonance assignments of the C-terminal domain of 5
      enolpyruvylshikimate-3-phosphate synthase.

PMID- 12522315
TI  - 1H, 13C and 15N resonance assignments of an affibody-target complex.

PMID- 12522316
TI  - Backbone 1H, 15N and 13C resonance assignments of the Staphylococcus aureus acyl
      carrier protein synthase (AcpS).

PMID- 12522317
TI  - Assignment of backbone 1H, 13C, and 15N resonances of the SH2 domain of human
      Grb14.
AB  - The (1)H, (13)C, and (15)N backbone resonance assignments have been made for the
      Src homology 2 (SH2) domain of the human molecular adapter protein Grb14. The
      assignments, along with the majority of the non-aromatic side-chain (1)H and
      (13)C resonances are reported. The SH2 domain has been complexed with a
      phosphotyrosine-containing peptide (pY766) corresponding to the putative binding
      site in the fibroblast growth factor receptor (FGFR1). Chemical shift changes
      upon binding are also reported.

PMID- 12522318
TI  - [Measurement of serum eosinophil cationic protein levels in wheezing infants].
AB  - Many infants have episode of wheezing. Some infants will outgrow the condition in
      early childhood, but some of them will become asthmatic. However, it is difficult
      to predict whether the wheezing infant is subsequently likely to experience
      bronchial asthma. To determine whether eosinophil inflammation is present in
      wheezing infants and can predict the development of asthma, serum eosinophil
      cationic protein (ECP) levels were measured in 33 infants who could not be
      diagnosed typical asthma, and 11 controls. Serum ECP levels were higher in the
      infants who had asthma within 3 months follow-up period. In addition, all 17
      infants with serum ECP levels above 20 ng/ml developed asthma within 3 months.
      The data suggested that serum ECP measurements appear to be useful for
      identifying infants with wheezing at high risk for infantile asthma.

PMID- 12522319
TI  - [Two cases of minocycline-induced vasculitis].
AB  - We report two cases of drug-induced vasculitis subsequent to long-term
      minocycline therapy. Case 1; A 27-year-old woman, who was receiving minocycline
      hydrochloride for eosinophilic pustular folliculitis of 68-months'duration,
      showed polyarthralgia, intermittent low-grade fever, and light red reticulated
      erythemas with subcutaneous nodules on her extremities. Case 2; A 31-year-old man
      developed reddish-brown, reticulated erythemas with induration on bilateral lower
      legs after 24-months' duration of minocycline hydrochloride treatment for
      hidradenitis suppurativa. In both cases, skin biopsies demonstrated vasculitis
      affecting a small-sized artery at the border of the dermis and subcutis. Serum
      antineutrophil cytoplasmic antibodies (ANCA) showed borderline elevation. In both
      cases cessation of minocycline administration resulted in rapid improvement of
      cutaneous lesions and constitutional symptoms. Recently, attention has been
      focused on drug-induced ANCA-positive vasculitis. Accumulation of previous case
      reports of minocycline-induced vasculitis with cutaneous lesions disclosed that
      the duration of the treatment before clinical symptoms averaged 35 months.
      Patients may present with livedoid skin lesions accompanied by fever,
      polyarthritis, autoimmune hepatitis and drug-induced lupus. Early recognition of
      ANCA-positive vasculitis is essential during long-term minocycline treatment,
      because cessation of the drug can result in complete resolution.

PMID- 12522320
TI  - [Quality of life in patients with atopic dermatitis: using the Japanese version
      of the SF-36 health status questionnaire].
AB  - Atopic dermatitis is a common skin disorder with an age onset mainly from infancy
      to adolescence. Patients with this disorder usually have a long history of
      repeated relief and relapse. The aim of the present studies is to quantify the
      relationship between the QOL score of patients and symptomatic characteristics
      (including severity measured by SF-36). From November 2000 to February 2001, the
      study recruited 281 patients with atopic dermatitis who had been treated at the
      Nagano dermatology and allergology clinic. The results of this study demonstrated
      that the symptoms severity and pruritus grade had strong influences on QOL score,
      and the location of pruritic lesion on the neck had the strongest influence on
      their self-perceived health status. The patients group with moderate atopic
      dermatitis who showed pruritus lesion in face, neck, and or knee, and female had
      consistently lower scores than male on all of the subscales. In conclusion, it is
      critically important to control of pruritus, and to develop an appropriate
      management.

PMID- 12522321
TI  - [Usefulness of patient education and quality of life (QOL) evaluation in asthma
      patients].
AB  - Achieving successful treatment of bronchial asthma depends on its control by the
      patient. We implemented a program of educating asthma patients and conducted a
      QOL survey to objectively evaluate the patients'conditions. Thirty-nine asthma
      patients who were receiving treatment with an inhaled corticosteroid
      [beclomethasone dipropionate (BDP) ] on an outpatient basis at our hospital,
      received instructions on proper drug administration in cooperation with the
      Pharmacy department of our hospital. The QOL survey (SF-36 and Marks et al. AQLQ)
      was conducted at the initial education session and again two months later. Thirty
      two patients (82.0%) responded that they would like to continue to receive
      instructions on the administration of drugs. Significant improvements in Social,
      Concerns, Marks, and Scales were observed after the education. In addition, even
      those patients who stated that they did not want to receive instructions showed
      significant improvements in their QOL scores. The usefulness of patient education
      can be assessed by the change in the patients' QOL scores.

PMID- 12522322
TI  - [A case of neonatal severe hypereosinophilia associated with mesalazine
      administered during pregnancy].

PMID- 12522323
TI  - New antiobesity agents in type 2 diabetes: overview of clinical trials with
      sibutramine and orlistat.
AB  - Besides genetic predisposition, obesity is the most important risk factor for the
      development of type 2 diabetes mellitus. Even modest weight reduction can improve
      blood glucose control in overweight subjects. After failure of lifestyle
      modifications, antiobesity drugs such as orlistat, a potent and selective
      inhibitor of gastric and pancreatic lipases that reduces lipid intestinal
      absorption, or sibutramine, a noradrenaline and 5-hydroxytryptamine reuptake
      inhibitor that regulates food intake, may be considered to favour weight loss
      and/or weight maintenance. Several placebo-controlled studies have recently
      demonstrated that both drugs are able to promote weight loss in obese type 2
      diabetic patients treated with diet alone, sulphonylureas, metformin or insulin.
      The greater weight reduction as compared to placebo was associated with a
      significant reduction of glycated haemoglobin levels and/or of the doses of
      classical antihyperglycaemic agents, especially in good responders who lost at
      least 10% of initial body weight. In addition, vascular risk factors associated
      to insulin resistance were also reduced after weight loss. These antiobesity
      agents may also contribute to delay or prevent the progression from impaired
      glucose tolerance to overt type 2 diabetes in at risk obese individuals ("Xenical
      in the prevention of diabetes in obese subjects" trial). Large long-term
      prospective studies, such as the "Sibutramine cardiovascular and diabetes outcome
      study" should better determine the place of pharmacological anti-obesity strategy
      in the overall management of obese patients with impaired glucose tolerance or
      type 2 diabetes.

PMID- 12522324
TI  - Improved beta cell function after short-term treatment with diazoxide in obese
      subjects with type 2 diabetes.
AB  - OBJECTIVE: Our aim was to distinguish beneficial effects of B-cell rest from
      other effects of correction of hyperglycaemia. For this purpose we used diazoxide
      which reversibly blocks insulin secretion. MATERIAL AND METHODS: Eight obese (age
      53 +/- 1 yr: BMI 33 +/- 2 kg/m2: 4 females) type 2 diabetic patients with poor
      metabolic control (HbA1c 8.7 +/- 0.9% ref.<5.2%) were studied twice after a
      randomly ordered treatment period of five days of intensive i.v. insulin
      treatment alone or i.v. insulin with peroral diazoxide (300 mg/day, divided into
      3 doses). The glycaemic control was not altered between the two treatment
      periods. Insulin secretion was measured in response to i.v. glucose and arginine.
      RESULTS: Insulin infusion was used to achieve close to identical degrees of
      glycaemia during the two treatment periods. Previous treatment with diazoxide was
      associated with a moderate 1.9 +/- 0.6 fold rise in insulin response to
      intravenous glucose (p=0.04) and 1.6 +/- 0.4 fold increased glucose potentiation
      of arginine-induced insulin secretion (GPAIS) (p=0.04). Conversely, after insulin
      alone there was no response to i.v. glucose and no change in GPAIS. CONCLUSIONS:
      Short-term diazoxide treatment improved important parameters of B-cell function
      and these effects could be dissociated from confounding effects of changes in
      glycaemia. Consequently, the results indicate beneficial effects of B-cell rest.

PMID- 12522325
TI  - Comparison between monofilament, tuning fork and vibration perception tests for
      screening patients at risk of foot complication.
AB  - OBJECTIVE: To compare normal and pathologic values of three different tests for
      screening patients at risk of foot complications: mono-filament, tuning fork and
      vibration threshold perception (VTP). METHODS: Two hundred and fifty consecutive
      patients followed-up in a diabetic clinic were screened for sensitive
      polyneuropathy by three different tests in three different examinations in a
      blind design. The 10 g mono-filament, tuning fork and Horwell neuro-esthesiometer
      were applied to different sites on the patients' legs and feet. RESULTS: Thirty
      eight patients were identified having abnormal tests and being at risk of foot
      complications using the mono-filament test; 33 of them and 9 more (42 patients
      (33 + 9)) were identified using the tuning fork applied to the malleolus and
      eight more (50 patients (33 + 9 + 8)) when the tuning fork was applied to the big
      toe; twenty more patients (70 (33 + 9 + 8 + 20)) were identified as being at risk
      using the VTP at a cut-off of 25 V. CONCLUSION: The mono-filament test identified
      patient with the highest risk of foot complications, but 37 more patients were
      identified to be at risk from a VTP > 25 V. These patients were not detected
      using the mono-filament test. The VTP test provides numerical values that can
      help to follow the course of the risk for foot insensitivity by allowing the care
      team to grade the education and follow-up of the at-risk group.

PMID- 12522326
TI  - Incidence of type 1 diabetes in children (0-14 years) in Benghazi Libya (1991
      2000).
AB  - BACKGROUND: Incidence of Type 1 diabetes in 0-14 year olds in Benghazi (Libya)
      during the period 1981-1990 was 7.0/10 5. The aim of this study is to report the
      incidence of Type 1 diabetes in 0-14 year olds in Benghazi Libya during the
      period 1991-2000. METHODS: Incidence data are based on prospective registration
      of Type 1 diabetes new cases for the period 1991-2000 in Type 1 register.
      RESULTS: A total of 276 (males 117, females 159) Type 1 diabetes new cases 0-14
      years of age were identified during the period 1.01.1991-31.12.2000. Completeness
      of ascertainment was 100%. The average annual incidence per year was 7.8/100,000
      population (95% CI 6.91-8.78). The standardized incidence rate (World standard)
      was 8.3/100,000 (95% CI 7.36-9.35). There was excess risk for females (9.1 95% CI
      7.77-10.65) versus males (6.6 95% CI 5.45-7.89) (p<0.001). No significant
      temporal trend was observed, yet there was an increase in incidence rate over
      that reported for the period 1981-1990 (7.8 vs 7.0). Seasonal variation in
      incidence was significant. CONCLUSION: It was concluded that the incidence of
      Type 1 diabetes in Benghazi is in the middle of the worldwide range close to the
      incidence in Mediterranean countries.

PMID- 12522327
TI  - Brazilian individuals with impaired glucose tolerance are characterized by
      impaired insulin secretion.
AB  - BACKGROUND: To better understand the pathogenesis of type 2 diabetes mellitus,
      insulin secretion and insulin sensitivity (IS) were evaluated in white Brazilians
      with impaired glucose tolerance (IGT), using the oral glucose tolerance test
      (OGTT) and the hyperglycemic clamp technique. METHODS: Twenty-five IGT subjects
      were individually matched with normal glucose-tolerant (NGT) subjects for
      demographic characteristics. At first, they were submitted to the OGTT and plasma
      glucose and insulin were measured. Of the 25 pairs, 20 could participate in the
      hyperglycemic clamp procedures, at a second visit. All participants had their
      plasma glucose levels equally increased to 180 mg/dl; this was maintained for
      three hours by variable glucose infusion. During the procedure, plasma glucose
      and insulin were measured at established intervals. RESULTS: In the
      postabsorptive state, the IGT subjects presented higher levels of plasma glucose,
      blood HbA1, and serum triglycerides, but similar plasma insulin levels. After the
      oral glucose load, early and total insulin release, in relation to glucose
      levels, were respectively, 43 and 67% lower in the IGT individuals. The index of
      whole-body IS was increased in the IGT individuals (4.36 +/- 1.71 vs 3.61 +/-
      1.28 mg(-1). micro U(-1).100.ml2; p<0.05). By the hyperglycemic clamp technique
      first- (82 +/- 26 vs 215 +/- 88 micro U/ml; p<0.001) and second- (36 +/- 19 vs 73
      +/- 44 micro U/ml; p<0.05) phases of insulin secretion was decreased in the IGT
      individuals, especially the first one. However, the groups did not differ in
      relation to the IS: IGT=13.52 +/- 7.27 and NGT=9.96 +/- 6.70 mg.ml/kg. micro
      U.min(-1); p > 0.05. Functional relationship of IS (y) on first-phase insulin
      release (x) showed a smaller (p<0.05) regression coefficient for the IGT group.
      CONCLUSION: Brazilians with IGT well-matched with NGT ones were characterized by
      impaired first- and second-phase insulin secretion (mainly the former), while
      defects in IS were not evident.

PMID- 12522328
TI  - Outcome of severe diabetic foot ulcers after standardised management in a
      specialised unit.
AB  - OBJECTIVE: The primary objective was to evaluate the efficacy in terms of limb
      salvage and healing time of standardised multidisciplinary management for high
      grade diabetic foot ulcers. The secondary objective was to retrospectively
      identify the factors that influenced time to healing. STUDY DESIGN AND METHODS:
      Over a 2-year period, 157 patients with diabetic foot ulcers were managed in our
      specialised unit using a standard treatment strategy; 118 were followed until
      healing or for at least 7 months (range, 7-29) after hospital discharge and form
      the basis for this study. Predetermined criteria were used to diagnose and manage
      the lesions. The number of major amputations and the time to healing were the
      main outcome measures. Univariable and multivariable analyses were done
      retrospectively to look for factors associated with time to healing. RESULTS: The
      limb salvage rate was 97.5% and the healing rate was 50% after 10 months and 70%
      after 16 months. Factors significantly associated with healing time were arterial
      disease without bypass surgery (p<0.001) and renal replacement therapy (p<0.05).
      Osteomyelitis, as managed in this study, did not increase the healing time (p >
      0.6). CONCLUSION: In high-grade diabetic foot ulcers, standardised conservative
      management with second-line bone-sparing surgery, if needed, yields an acceptable
      limb salvage rate. With combined medical and surgical treatment, osteomyelitis is
      not a poor prognosis factor.

PMID- 12522329
TI  - Diagnosis of osteomyelitis in the diabetic foot with a 99mTc-HMPAO leucocyte
      scintigraphy combined with a 99mTc-MDP bone scintigraphy.
AB  - BACKGROUND: The aim of this prospective study was to assess the role of 99mTc
      HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy in the
      diagnosis of the diabetic foot infection (HMPAO-Leu/MDP). METHODS: 75 diabetic
      patients with suspected osteomyelitis were included. The HMPAO-Leu/MDP scan was
      considered to be consistent with osteomyelitis when the HMPAO-Leu uptake was
      concordant in all the incidences with an MDP bone uptake. A HMPAO-Leu uptake
      without concordant bone MDP activity was considered as a soft-tissue infection.
      The results of the HMPAO-Leu/MDP scan were compared to the following diagnostic
      criteria: bone infection was confirmed by radiological follow-up or bone biopsy;
      the absence of bone infection was confirmed by clinical (healing of the ulcer
      without antibiotherapy) and radiological follow up. RESULTS: According to these
      criteria, among the 83 ulcers, bone infection was observed in 41 (49.4%): the
      HMPAO-Leu/MDP scan was positive in 38 cases, including 14 ulcers with normal or
      doubtful radiographs at inclusion. In the group of 42 ulcers without proven bone
      infection, the HMPAO-Leu/MDP scan was negative in 41 cases, including 17 lesions
      with a soft-tissue infection. CONCLUSION: With a sensitivity of 92.6%, a
      specificity of 97.6%, the HMPAO-Leu/MDP scan is a reliable tool for the diagnosis
      of osteomyelitis in the diabetic foot. Neuroarthropathy did not affect the
      performances of the HMPAO-Leu/MDP scan. Owing to a high spatial resolution this
      test is very helpful to differentiate bone infection from soft-tissue infection
      especially in case of neuroarthropathy.

PMID- 12522330
TI  - Type 2 diabetes mellitus among beneficiaries of the french national health
      insurance for self-employed workers (AMPI): comparison of the management of
      craftsmen or tradesmen with professionals patients.
AB  - BACKGROUND: Although the management of diabetes mellitus varies according to non
      medical factors, the influence of socioprofessional category has been not fully
      studied. This study compared the management of type 2 diabetes mellitus in
      craftsmen or tradesmen with professionals categories. METHODS: All claims to the
      French National Sickness Insurance Fund for self-employed workers (AMPI) from its
      mainland France beneficiaries in 1998 were retrospectively analysed. Patients
      were beneficiaries, insured or dependants of craftsmen or tradesmen, or
      professionals receiving oral hypoglycemic drugs during a 3-month inclusion
      period. Patients were compared on the proportion of care received in private
      practice over the preceding 12 months using adjusted odds ratio (OR). RESULTS:
      Compared to patients in professionals (n=1,456), patients in craftsmen or
      tradesmen (n=35,703) were statistically more likely to see a general practitioner
      (OR 3.867, 95% CI=3.048; 4.907), to have blood glucose test (OR 1.530, 95%
      CI=1.332; 1.757) and serum creatinine assay (OR 1.207, 95% CI=1.052; 1.270). They
      were statistically less likely to consult or have a specialist procedure
      (ophthalmologist, OR 0.792, 95% CI=0.698; 0.900; cardiologist, OR 0.749, 95%
      CI=0.658; 0.852; dentist, OR 0.679, 95% CI=0.596; 0.773; endocrinologist, OR
      0.522, 95% CI=0.424; 0.642), microalbuminuria test (OR 0.749, 95% CI=0.622;
      0.902) and serum creatinine assay or microalbuminuria test (OR 0.746, 95%
      CI=0.611; 0.912). The two groups did not differ on HbA1c, blood lipid tests and
      electrocardiogram. CONCLUSIONS: The management of type 2 diabetes mellitus
      differed between craftsmen or tradesmen and professionals patients. These results
      should be confirmed.

PMID- 12522332
TI  - Type 2 diabetes mellitus in the French overseas departments and territories: the
      "syndrome of Nauru".

PMID- 12522331
TI  - Failure of angiotensin II and insulin to stimulate transforming growth factor
      beta1. Release from cultured bovine retinal pericytes.
AB  - BACKGROUND: Activation of the renin-angiotensin system (RAS) may induce
      cardiovascular and renal fibrosis in hypertension and diabetes. This fibrogenic
      effect is mainly mediated by Transforming Growth Factor-B1 (TGF-B1), a
      multifunctional citokyne released by endothelial, vascular smooth muscle and
      renal mesangial cells, that is able to increase extracellular matrix deposition.
      Retinal capillary pericytes have functions similar to those of mesangial cells,
      including ability to synthesize and release TGF-B1 and produce extracellular
      matrix. An intraocular RAS was described in the human eye and may produce effects
      similar to those observed in the heart and kidney, which could be mediated by TGF
      B1. In particular, TGF-B1 might be involved in thickening of the capillary
      basement membrane in diabetic microangiopathy. We therefore aimed at evaluating
      the possible effects of Angiotensin-II on TGF-B1 secretion by cultured retinal
      pericytes (BRP). METHODS: BRP cultures were incubated with Angiotensin-II or
      insulin (known to play a permissive effect on TGF-B1 release from mesangial
      cells) or Angiotensin-II + insulin at final concentrations of 10-10, 10-8, 10-6,
      10-4 mol/L. RESULTS: Baseline TGF-B1 concentrations in the supernatants of
      pericyte cultures were 6 139 +/- 1 919 pg/mL/106 cells; no changes of TGF-B1
      concentrations resulted from adding increasing amounts of Ang II, insulin or
      both. CONCLUSIONS: Though confirming that cultured bovine retinal pericytes
      spontaneously release TGF-B1, Angiotensin-II did not produce any stimulatory
      effects of in our experimental system

PMID- 12522333
TI  - Interference of dapsone in HbA1c monitoring of a diabetic patient with
      polychondritis.

PMID- 12522336
TI  - [X-ray tube equipped with a carbon-nanotube electron source].

PMID- 12522337
TI  - [Luncheon seminar: great hopes for introducing a new "clinical professor"
      institution into an educational system of radiological technology].

PMID- 12522334
TI  - [Clinical relevance of homocysteine monitoring in the diabetic patient].
AB  - Accelerated atherosclerosis is common in diabetes mellitus, although its extent
      is not always related to its strong association with classical cardiovascular
      risk factors. Diabetic patients, especially with type 2 diabetes, are prone to
      cardiovascular disease which is the leading cause of death in this population.
      Recent clinical studies among general population have shown that an even mild
      increase of homocysteinemia play an important role in the progression of
      atherosclerosis, either in coronary or peripheral arteries. An increasing amount
      of in vitro data is providing evidence that excess of homocysteine has a toxic
      effect on the arterial wall. This aminoacid thus appears to be not only a risk
      marker but also an emerging cardiovascular risk factor. The measurement of plasma
      homocysteine contributes to the identification, among the diabetic population, of
      patients at high cardio-vascular risk, with the aim of improving their global
      management. Moreover the addition of group B vitamins provides an easy and low
      cost treatment to lower hyperhomocysteinemia.

PMID- 12522338
TI  - [Temporal measurement of imaging properties of screen-film systems].

PMID- 12522339
TI  - [New proposal and problems for radiological protection by new ICRP
      recommendation].

PMID- 12522340
TI  - [2001 Standardization committee activities].

PMID- 12522342
TI  - [Apparatus engineering of x ray CT equipment (2) : image reconstruction and image
      display].

PMID- 12522341
TI  - [The notes of the measuring average glandular dose].

PMID- 12522343
TI  - [From "teaching" to "learning" : "pains" with fundamental principle and/or
      appointment rule].

PMID- 12522344
TI  - [Dry-imager for medical use (1)].

PMID- 12522345
TI  - [A comparison between physicians' interpretation and a CAD system's cancer
      detection by using a mammogram database in a physicians' self-learning course].
AB  - We have been developing automated detection algorithms for masses and clustered
      microcalcifications in a mammography computer-aided diagnosis (CAD) system. In
      this study, we investigated the potential of our CAD system by comparing 579
      physicians' interpretation results with that of the CAD system's cancer detection
      for 100 mammograms (21 malignant and 29 benign cases) employed in a physicians'
      self-learning course. As a result, our CAD system detected 7 out of 8 malignant
      lesions whose physicians' averaged sensitivity was less than 60%. Although the
      average of physicians' sensitivities were 76% (about 16 cases), the CAD system's
      detection rate was 90% (19 cases). Sensitivity was raised up to 97% if the
      physicians' interpretation and the CAD system's detection result were treated in
      a matter of logical OR. Thus, it was raised the possibility that even the less
      experienced physicians would diagnose with a higher sensitivity by using the
      computer output as a guide effectively.

PMID- 12522346
TI  - [An absorbed dose conversion factor due to the x-ray spectrum compare with the
      method by the half-value layer].
AB  - When the absorbed dose conversion factor of the x-rays is looked for, generally
      it is being done how to measure the effective energy (keV) from the half-value
      layer. But, spectrum measurement is necessary to evaluate quality of x-ray
      precisely. So, 2.94% of the maximum differences were in the water, soft tissue,
      and 20.93% of the maximum differences were in search of absorbed dose conversion
      factor due to the half-value layer and the spectrum as a compared result by
      cortical bone. And, when a x-ray tube voltage rose, this difference showed a
      tendency of spreading out. A cause was because the rates of the photon of the
      higher energy than the energy measured with effective energy increased by a x-ray
      tube voltage's rising. The ratio of the mass energy absorption coefficient which
      faces air like cortical bone should be careful because an error by the absorbed
      dose conversion factor grows big when a absorbed dose conversion factor is
      measured by the big absorption medium, though it is as the difference in absorbed
      dose conversion factor is compared with an error by the dosimeter and there is no
      problem in the water, soft tissue.

PMID- 12522347
TI  - [Studies of the projection for carpometacarpal joint of the thumb that considered
      patient burden].
AB  - The carpometacarpal joint of the thumb is the most important in manual exercise
      function. Robert method is used for the projection for carp metacarpal joint of
      the thumb broadly. But, the physique is difficult when there is a pain to a
      person of advanced age and an upper drumstick in Robert method. So, we devised
      the photography method that reduced patient burden. Comparison examined Robert
      method and Tokai method. Detect ability is equal in both method. Patient burden
      is reduced in Tokai method. Therefore, it isn't influenced a state of patient,
      and application range is useful broadly.

PMID- 12522348
TI  - [An automated detection of lacunar infarct regions in brain MR images:
      preliminary study].
AB  - The purpose of this study is to develop a technique to detect lacunar infarct
      regions automatically in brain MR images. Our detection method is based on the
      definition of lacunar infarcts. After inputted images were binarized, we used
      feature values such as area, circularities and the center of gravity of candidate
      regions to extract isolated lacunar infarct regions. We also developed and used a
      new filter to enhance the signals of lacunar infarcts adjacent to some high
      intensity regions. 10 cases involving 81 sectional images were applied to our
      experiment. As a result, the sensitivity was 100% with approximately 1.77 false
      positives per image. Our results are promising on the first stage, although it
      remains to improve on problems that to eliminate false-positives and
      automatically establish threshold value.

PMID- 12522349
TI  - [Removal of high signal artifact (marching metal artifact) by the magnetic
      substance].
AB  - During this project, we evaluated methods to prevent high-signal artifact
      (marching metal artifact) that are caused by magnetic substance. Marching metal
      artifact is caused by the resonance frequency created by magnetic substance.
      Phase encoding and frequency encoding are often switched to minimize the
      influence that marching metal artifact have on the image. However, this method
      will only change the position at which marching metal artifact occur. It does not
      have the ability to completely prevent marching metal artifact. Our research
      illustrated that marching metal artifact can be prevented by changing the
      strength of the slice selective gradient field at the 90 degree RF pulse and 180
      degree RF pulse. In other words, marching metal artifact can be prevented by
      changing the frequency bandwidth for the 90 degree RF pulse and 180 degree RF
      pulse. The incorporation of the phase correct option in the device used for our
      research (SIGNA LX and SIGNA CV/i) results in different slice selective gradient
      field strengths at the 90 degree RF pulse and the 180 degree RF pulse. This
      indicates that the use of phase correction enables marching metal artifact to be
      prevented.

PMID- 12522350
TI  - [A design of the measuring chart for magnifying-power compensation in brain
      angiography].
AB  - PURPOSE: When brain angiography was performed, we devised the calculation theory
      for rectifying magnifying power, and produced the auxiliary tool. METHOD: We
      produced the frame with a size of 300 x 300 x 15 mm from the thin board made from
      carbon. The frame is around arranged for every 1 cm in Pb-ball of the diameter of
      1 mm. We named this the measuring-chart. The measuring-chart has been arranged so
      that head may be surrounded. A photograph of a measuring-chart and head was taken
      simultaneously. The projected mark used for computing the magnifying power of a
      brain aneurysm. Magnifying power was used in order to measure the size of an
      aneurysm. RESULTS: In the basic experiment using the stainless-steel ball whose
      size is known, the standard error was -2.29% +/- 5.61%. A measurement value and
      true value showed high correlation (R(2) = 0.9986). CONCLUSION: The measuring
      chart did not need a proofreading factor peculiar to equipment. This method had
      high accuracy. This method has high flexibility. It suggested that this method
      was useful on clinical use.

PMID- 12522351
TI  - [Measurement of patient skin dose in interventional radiology using radiochromic
      reflecting-type sheet films].

PMID- 12522353
TI  - Purchasing that new helicopter, part 1.

PMID- 12522354
TI  - The role of transport teams in pediatric injury prevention.

PMID- 12522356
TI  - Medical direction and medical control of air medical services: position statement
      of the Air Medical Physician Association approved by the AMPA Board of Trustees
      October 1998, revised April 2002.

PMID- 12522357
TI  - REACH Air Ambulance: built on innovation, committed to excellence.

PMID- 12522358
TI  - A progressive curriculum in air medical transport for nursing and paramedic
      students.

PMID- 12522359
TI  - An analysis of the proposed national strategy for smallpox vaccination of health
      care workers.

PMID- 12522360
TI  - Air sickness in flight: frequency and factors.

PMID- 12522361
TI  - Use of the endotracheal tube introducer as an adjunct for oral tracheal
      intubation in the prehospital setting.
AB  - OBJECTIVE: To prospectively evaluate the effectiveness of the endotracheal tube
      introducer (ETTI) versus standard orotracheal intubation (SOTI) in the
      prehospital air medical setting. METHODS: Critically ill patients were randomized
      to ETTI versus SOTI based on an odd/even day regimen. Data were collected on
      initial intubation attempt used, success using initial approach, number of
      intubation attempts until success, and laryngeal view encountered. The 2
      approaches then were compared and statistically analyzed. RESULTS: Fifty-one
      patients were entered into the 10-month study; 20 patients were randomized to the
      ETTI group and 31 to SOTI. Overall success rate for first intubation attempt was
      70% for the ETTI and 65% SOTI (P =.67). Total intubation time was 62 seconds (95%
      CI = 16-108) for the ETTI versus 62 seconds (95% CI = 38-86) for SOTI (P =.4).
      The ETTI group had a higher percentage of intubating difficult laryngeal views
      (grade 3 and 4) on first attempts than SOTI. CONCLUSION: In this study, the
      authors found the ETTI to be a safe airway adjunct with results equal to SOTI.
      The ETTI may have a useful role in prehospital airway management.

PMID- 12522362
TI  - The sternal IO and vascular access-any port in a storm.

PMID- 12522365
TI  - Cutaneous photodamage, oxidative stress, and topical antioxidant protection.
AB  - New methods to protect skin from photodamage from sun exposure are necessary if
      we are to conquer skin cancer and photoaging. Sunscreens are useful, but their
      protection is not ideal because of inadequate use, incomplete spectral
      protection, and toxicity. Skin naturally uses antioxidants (AOs) to protect
      itself from photodamage. This scientific review summarizes what is known about
      how photodamage occurs; why sunscreens--the current gold standard of
      photoprotection--are inadequate; and how topical AOs help protect against skin
      cancer and photoaging changes. This review is intended to be a reference source,
      including pertinent comprehensive reviews whenever available. Although not all
      AOs are included, an attempt has been made to select those AOs for which
      sufficient information is available to document their potential topical uses and
      benefits. Reviewed are the following physiologic and plant AOs: vitamin C,
      vitamin E, selenium, zinc, silymarin, soy isoflavones, and tea polyphenols. Their
      topical use may favorably supplement sunscreen protection and provide additional
      anticarcinogenic protection. (J Am Acad Dermatol 2003;48:1-19.) LEARNING
      OBJECTIVE: At the completion of this learning activity, participants should have
      an understanding of current information about how the sun damages skin to produce
      skin cancer and photoaging changes, how the skin naturally protects itself from
      the sun, the shortcomings of sunscreens, and the added advantages of topical AOs
      for photoprotection.

PMID- 12522366
TI  - Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides:
      serum TARC levels reflect the disease activity of mycosis fungoides.
AB  - BACKGROUND: Mycosis fungoides (MF) belongs to cutaneous T-cell lymphoma and is
      clinically divided into 3 stages: patch, plaque, and tumor stage. Thymus and
      activation-regulated chemokine (TARC/CCL17) is a member of the CC chemokines and
      is a chemoattractant for CC chemokine receptor 4 (CCR4)- and CC chemokine
      receptor 8 (CCR8)-expressing cells. OBJECTIVE: In this study, we examined the
      involvement of TARC among patients with each stage of MF. METHODS: We
      investigated the expression of TARC, CCR4, and CXC chemokine receptor 3 in
      patients with each stage of MF by immunohistochemistry. We measured serum TARC
      levels in 20 patients with MF in varying degrees and compared them with 10
      patients with psoriasis vulgaris and 10 healthy controls. In addition, we
      compared serum TARC levels in patients with MF with other laboratory data.
      RESULTS: Immunohistochemical staining revealed that TARC was expressed in the
      lesional keratinocytes in the patch, plaque, and tumor stages. CCR4 was expressed
      on the epidermotropic cells in both patch and plaque stages and on the large cell
      transformed cells in the tumor stage, whereas CXC chemokine receptor 3 was
      constantly expressed on the small cells in the lesional dermis. Serum TARC levels
      in patients with MF were significantly higher than those in patients with
      psoriasis vulgaris or healthy controls. Moreover, serum TARC levels in patients
      with the tumor stage of MF (n = 5) were remarkably higher than those with patch
      stage (n = 8) or plaque stage (n = 7). Serum TARC levels significantly correlated
      with serum lactate dehydrogenase levels (r = 0.62), serum immunoglobulin E levels
      (r = 0.60), serum soluble interleukin 2 receptor levels (r = 0.72), and serum
      macrophage-derived chemokine levels (r = 0.70). CONCLUSION: These data strongly
      indicate that serum TARC levels are useful for assessing the disease activity of
      patients with MF and that TARC and CCR4 may be involved in the pathogenesis of
      MF.

PMID- 12522367
TI  - Schamberg's purpura in children: a review of 13 cases.
AB  - BACKGROUND: Schamberg's purpura (progressive pigmentary dermatosis or pigmented
      purpuric dermatosis) is uncommonly described in preadolescent children. PATIENTS
      AND METHODS: A retrospective review of cases of Schamberg's purpura with onset
      before 10 years of age was undertaken. Clinical and histopathologic data, as well
      as analytical studies including hemogram, erythrocyte sedimentation rate, serum
      chemistry, urinalysis, cryoglobulins, and screening for thrombotic and clotting
      disorders were recorded. RESULTS: A total of 13 patients (3 male and 10 female)
      from 1 to 9 years of age (median, 5 years) had the typical cutaneous features of
      Schamberg's purpura. The lower limbs were affected in all patients. Lesions were
      unilateral in 3 cases. In 4 patients, lesions faded within 1 to 4 years, and in 1
      patient lesions improved after 6 years. In 8 patients lesions persisted 1 to 7
      years after. Laboratory studies were normal in all patients. CONCLUSION:
      Schamberg's purpura is a chronic benign form of pigmented purpura which is
      occasionally seen before puberty.

PMID- 12522368
TI  - The first 15 years of the American Academy of Dermatology skin cancer screening
      programs: 1985-1999.
AB  - BACKGROUND: In response to the precipitous increase of melanoma, the American
      Academy of Dermatology (AAD) has coupled melanoma/skin cancer education with free
      skin cancer screening programs throughout the United States since 1985. The
      purpose of this analysis is to investigate the risk factors, access to
      dermatologic services, and screening results of participants in AAD-sponsored
      programs during the first 15 years that this service was available to the US
      public. METHODS: Before screening, participants completed a standardized AAD
      screening form. Screening forms were counted in the AAD central office and
      recorded in annual summaries. Forms were sent for keypunching and returned to the
      AAD on a computer disk annually. In 1999, disks were sent to Boston University
      and a master file was created. RESULTS: Computerized records were available for
      819,019 screening forms and 639,835 individuals. In all, 65% of screenees had at
      least 1 risk factor and 33% had at least 2 risk factors. Of screenees, 33%
      reported a changing mole and 37% had skin type I or II. Among all screenees,
      nearly 80% did not have a regular dermatologist, 78% reported no prior AAD skin
      cancer screening, 60% had never had their skin checked by any doctor, and 51%
      would not have seen a doctor for skin cancer without the free screening. Nearly
      30% of screenees had a presumptive diagnosis of skin cancer or a precursor
      lesion. Melanomas confirmed by postscreening biopsy were more likely than those
      in population-based registries to be less than 1.50 mm in thickness. CONCLUSIONS:
      AAD national screening and educational programs have expanded to all 50 states,
      provided educational messages about sun protection and early detection to
      millions, and served many US citizens with an above average risk for skin cancer
      and suboptimal access to dermatologic care. Screenees had a disturbingly high
      point prevalence of malignant and premalignant skin lesions. Sustained commitment
      by the AAD leadership and membership to the screening program is critical to
      reducing the morbidity and mortality of skin cancer.

PMID- 12522369
TI  - Clinical and pathologic features of nephrogenic fibrosing dermopathy: a report of
      two cases.
AB  - Nephrogenic fibrosing dermopathy is a rare, recently described fibrotic skin
      condition that primarily affects patients with a history of renal disease. We
      describe 2 patients on hemodialysis with the characteristic clinical and
      pathologic features. Nephrogenic fibrosing dermopathy should be distinguished
      from other fibrotic disorders, such as scleromyxedema, systemic sclerosis, and
      eosinophilic fasciitis

PMID- 12522370
TI  - Early onset of action and efficacy of a combination of calcipotriene and
      betamethasone dipropionate in the treatment of psoriasis.
AB  - BACKGROUND: Calcipotriene and betamethasone dipropionate are topical treatments
      for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit
      may result with concomitant use of the two compounds together. A new vehicle has
      been created with the objective of obtaining optimal stability of both
      calcipotriene and betamethasone dipropionate in the combination product.
      OBJECTIVE: We compared the clinical efficacy of a fixed combination of
      calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in
      the new vehicle, betamethasone in the new vehicle, and the new vehicle alone.
      METHODS: This was an international, multicenter, prospective, randomized, double
      blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable
      to topical treatment. RESULTS: The mean percentage reduction in PASI from
      baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8%
      in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate
      group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The
      mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%,
      and 21.5%, respectively (P < .001). CONCLUSION: A combination product of
      calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new
      vehicle shows superior efficacy with a more rapid onset of action than the new
      vehicle containing either constituent alone in the treatment of psoriasis
      vulgaris.

PMID- 12522371
TI  - Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease).
AB  - Nephrogenic fibrosing dermopathy or scleromyxedema-like illness of renal disease
      is a recently reported disorder. It manifests as scleromyxedema-like skin lesions
      without associated paraproteinemia, occurring in the setting of renal disease. In
      the majority of cases skin lesions of nephrogenic fibrosing dermopathy develop
      after hemodialysis or renal transplantation; however, the origin is still
      unknown. We report 4 new cases of nephrogenic fibrosing dermopathy and review the
      literature. The clinical and histopathologic features, differential diagnosis,
      possible etiology, and treatment options are reviewed.

PMID- 12522372
TI  - Actinic degeneration and pigmentary change in association with psoralen and UVA
      treatment: a 20-year prospective study.
AB  - BACKGROUND: Changes in the appearance of the skin including actinic degeneration
      and pigmentary changes have been noted in patients treated with psoralen and UVA
      (PUVA). OBJECTIVE: Our purpose was to quantify risk factors for increased extent
      and progression of actinic degeneration and pigmentary changes in the skin of
      patients treated with PUVA. METHODS: On the basis of standardized dermatologic
      examination conducted in 1977 and 1998 of patients enrolled in the PUVA Follow Up
      Study, we assessed the prevalence of and changes in the extent of actinic
      degeneration and pigmentary abnormalities on the hands and buttocks. RESULTS:
      From 1977 to 1998, the prevalence of moderate or severe actinic degeneration
      increased from 15.6% to 60.5% on the hands and from 2.2% to 21.3% on the
      buttocks. During this same period, the prevalence of pigmentary changes of this
      degree increased from 15.6% to 58.6% on the hands and 12.6% to 24.7% on the
      buttocks. Extent of exposure to PUVA was the strongest predictor of an increased
      extent of clinical actinic degeneration or pigmentary change. CONCLUSION: Long
      term exposure to PUVA is associated with persistent increases in actinic
      degeneration and pigmentary abnormalities of the skin on both usually sun-exposed
      and sun-protected sites.

PMID- 12522373
TI  - Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha
      monoclonal antibody (infliximab) treatment of moderate to severe psoriasis
      vulgaris.
AB  - OBJECTIVE: Infliximab monotherapy provided a rapid and high degree of clinical
      benefit in patients with moderate to severe psoriasis in a previously conducted
      trial. Herein we describe the pharmacodynamic and pharmacokinetic results
      observed in this clinical trial. METHODS: Patients with psoriasis received 5 or
      10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical
      analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was
      conducted. Median infliximab half-life and peak serum concentrations over time
      were calculated. RESULTS: Infliximab immunotherapy resulted in rapid and dramatic
      decreases in epidermal inflammation and normalization of keratinocyte
      differentiation in psoriatic plaques; these changes preceded maximal clinical
      response. Infliximab concentrations were maintained above the detection limit
      (0.1 mg/mL) in the majority of patients through week 14. CONCLUSION: The clinical
      and immunohistologic data demonstrate a pivotal role for tumor necrosis factor
      alpha in the pathogenesis of psoriasis and support further development of drugs
      targeting tumor necrosis factor-alpha.

PMID- 12522374
TI  - Treatment of reticular leg veins with a 1064 nm long-pulsed Nd:YAG laser.
AB  - BACKGROUND: Millisecond-pulsed Nd:YAG lasers have been developed for the
      treatment of reticular leg veins. OBJECTIVE: We evaluated the effectiveness of a
      single treatment with a 50 millisecond 1064 nm Nd:YAG laser in the treatment of
      reticular veins of the lower extremity. METHODS: Twenty patients with reticular
      veins measuring 1.0 to 3.0 mm in diameter received one treatment with a 1064 nm
      Nd:YAG laser (Coolglide, Altus, Burlingame, Calif) at fluences of 100 J/cm(2) and
      50 millisecond pulse duration. Symmetric matched areas that were left untreated
      served as the control. Eleven patients were pretreated with a topical anesthetic
      cream for 1 hour before treatment and wore compression stockings for 5 days after
      treatment. Nine patients were treated without topical anesthesia and did not wear
      compression stockings. Percent clearing and side effects were determined by 3
      nontreating physicians (at each respective site) comparing projected Kodachrome
      images 1 month and 3 months after treatment. Patients also performed a self
      assessment of their results. RESULTS: Two-thirds of vessels measuring 1 to 3 mm
      in diameter cleared more than 75% with one treatment. Larger vessels appeared to
      improve more than smaller vessels. Immediate treatment discomfort was tolerable.
      Side effects were minimal and included superficial thrombosis, delayed bruising,
      hyperpigmentation, and matting. CONCLUSION: Millisecond-pulsed Nd:YAG lasers used
      with 50 millisecond pulses are effective in the treatment of reticular leg veins.

PMID- 12522375
TI  - Multiple spindle cell lipomas and dermatofibrosarcoma protuberans within a single
      patient: evidence for a common neoplastic process of interstitial dendritic
      cells?
AB  - This case report describes a 48-year-old man with multiple spindle cell lipomas
      of the neck and a dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous
      transformation of the chest. The presence of familial and nonfamilial multiple
      spindle cell lipomas within a single patient is a rare event, with only two
      reports in the current literature. This case represents the first report of
      multiple spindle cell lipomas occurring in association with a DFSP. It is of
      particular interest in that both spindle cell lipoma and DFSP represent, at least
      in part, neoplastic proliferations of CD34(+) spindled cells. The exact nature
      and differentiation of these spindled cells remains controversial, but prior
      studies have suggested that they could represent neoplastic interstitial
      dendritic cells. The association of DFSP and spindle cell lipoma within this
      single patient suggests that these two tumors (and their histologic variants) may
      well be linked, conceptually, as neoplastic proliferations of CD34(+)
      interstitial dendritic cells.

PMID- 12522376
TI  - History and clinical significance of mechanical symptoms in blistering
      dermatoses: a reappraisal.
AB  - In the era before the advent of routine microscopy and immunopathology,
      mechanical symptoms were described in an attempt to facilitate clinical diagnosis
      of blistering dermatoses. A plethora of eponyms and signs were described, but no
      proper original quotations exist. All the eponyms haunt the student and
      specialist. In the case of an ominous and, therefore, very important clinical
      phenomenon termed the Nikolskiy sign, this creates confusion about the specific
      meaning of the term, obscuring diagnosis and delaying initiation of an adequate
      treatment of pemphigus. We try to set this record straight and go to the sources.
      Russian, German, French, and English, at the least, are required to properly
      interpret the relevant descriptions. We provide an accurate interpretation of the
      major mechanical symptoms pathognomonic for acantholysis, dermoepidermal
      separation, and peeling of the entire epidermis. Correct performance of the tests
      and proper interpretation of the results can serve as an invaluable diagnostic
      tool to assist in the preliminary bedside diagnosis of serious and potentially
      lethal bullous dermatoses.

PMID- 12522377
TI  - World Health Organization classification of hematopoietic and lymphoid tissues:
      implications for dermatology.
AB  - The new World Health Organization (WHO) classification of hematopoietic and
      lymphoid malignancy represents the first worldwide consensus document on the
      classification of lymphoma/leukemia. Its aim is to supercede all existing
      classification systems, including the Revised European American Classification
      (REAL), and the organ-based classification of cutaneous lymphoma proposed in 1997
      by the European Organization for Research and Treatment of Cancer (EORTC)
      cutaneous lymphoma project group. This article compares the REAL, EORTC, and WHO
      classifications with particular reference to cutaneous lymphoma. It identifies
      those entities that have been adopted from the EORTC classification, and
      illustrates important new entities in the category of cytotoxic T-/NK-cell
      lymphomas that characteristically present in the skin or subcutaneous tissue.
      However, WHO is not an organ-based classification and some categories (eg
      follicular B-cell lymphoma and peripheral T-cell lymphoma) include both cutaneous
      and systemic diseases, and these may have very different prognoses. It is,
      therefore, important that cancer registries are capable of recording sites of
      involvement for both B- and T-cell lymphomas so that the incidence and prognosis
      of cutaneous lymphomas can be established from national data sets in future
      years.

PMID- 12522379
TI  - Facial papules, spontaneous pneumothorax, and renal tumors.

PMID- 12522378
TI  - Summary of North American Hair Research Society (NAHRS)-sponsored Workshop on
      Cicatricial Alopecia, Duke University Medical Center, February 10 and 11, 2001.

PMID- 12522380
TI  - Surgical pearl: the use of a wooden toothpick for the removal of a specimen from
      the biopsy site.

PMID- 12522381
TI  - Pemphigus herpetiformis with IgA and IgG antibodies to desmoglein 1 and IgG
      antibodies to desmocollin 3.
AB  - We describe a case with clinical and histologic features of pemphigus
      herpetiformis associated with IgG and IgA anti-keratinocyte cell surface
      antibodies to desmoglein 1 (Dsg1) and exclusively IgG antibodies to desmocollin 3
      (Dsc3). The clinical presentation was somewhat similar to IgA pemphigus; the main
      difference was the prevailing association with IgG antibodies to Dsg1. The
      presence of IgA anti-Dsg1 antibodies was confirmed by IgA enzyme-linked
      immunosorbent assay and IgG anti-Dsc3 antibodies were detected by a novel enzyme
      linked immunosorbent assay with the use of baculovirus expressing recombinant
      Dscs for IgG and IgA. The reactivity of IgG antibodies with Dsc3 was confirmed by
      COS-7 cell cDNA transfection method using cDNA of human Dsc1 to Dsc3. We discuss
      the differentiation of pemphigus herpetiformis, associated with both IgG and IgA
      antibodies, from IgA pemphigus, particularly in regard to the autoimmune reaction
      with Dsgs and Dscs.

PMID- 12522382
TI  - Disseminated blastomycosis.
AB  - A 26-year-old veiled Saudi-Arabian woman presented with hemoptysis, and multiple
      nodules and abscesses. A skin biopsy specimen revealed yeast forms consistent
      with Blastomyces dermatitidis. Fungal cultures from bronchoscopy and skin
      specimens also grew B dermatitidis. She was treated with oral itraconazole (200
      mg twice a day). Both lung and skin lesions showed improvement within 6 weeks.

PMID- 12522383
TI  - Validation of the Dermatology Life Quality Index and the Work Productivity and
      Activity Impairment-Chronic Hand Dermatitis questionnaire in chronic hand
      dermatitis.
AB  - In a double-blind, randomized trial of 257 patients with chronic hand dermatitis,
      the validity, reproducibility, and responsiveness of the Dermatology Life Quality
      Index and the Work Productivity and Activity Impairment questionnaire were
      established, and the sample size required to detect meaningful differences
      between treatment groups was estimated.

PMID- 12522384
TI  - Giant right plantar keloid treated with excision and tissue-engineered allograft.
AB  - Plantar keloids are a management problem as a result of the pain and mechanic
      restriction with ambulation. We present the treatment of a patient with a
      particularly large plantar keloid that was refractory to multiple excisions,
      adjunctive intralesional steroids, and radiation therapy, who was successfully
      treated with excision, intralesional steroids, and tissue-engineered allograft
      placement.

PMID- 12522385
TI  - Trials, evidence, and the management of patients with psoriasis.

PMID- 12522386
TI  - The meaning of "safe and effective".

PMID- 12522387
TI  - Disseminated Mediterranean Kaposi sarcoma treated with low-dose recombinant
      interferon alfa-2a.

PMID- 12522388
TI  - Linear sebaceous gland hyperplasia of the penis: a case report.

PMID- 12522389
TI  - Pediatric sarcoidosis.

PMID- 12522393
TI  - Solitary intra-articular tumoral calcinosis of the knee.
AB  - An unusual case of symptomatic, solitary, intra-articular tumoral calcinosis of
      the knee in a 39-year-old man is presented. This is the first reported case of
      intra-articular tumoral calcinosis with no associated underlying systemic
      diseases. Magnetic resonance imaging was helpful in delineating the lesion.
      Surgical excision resulted in resolution of symptoms and was not followed by
      recurrence of the lesion.

PMID- 12522394
TI  - Proprioception of the knee before and after anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: The purpose of this study was to determine, first, if there is
      measurable deficit in proprioception in an anterior cruciate ligament (ACL)
      deficient knee, either compared to the contralateral knee or external controls;
      second, if this deficit, if present, improves after ACL reconstruction; and
      third, if improvement occurs, what the time course of improvement is. TYPE OF
      STUDY: Prospective cohort study. METHODS: Patients undergoing ACL reconstruction
      at the University of Chicago, demonstrating a full and painless range of motion
      and no other knee ligament injury or history of previous knee surgery, were
      eligible. Twenty-six patients, with an average age of 25 years (range, 16 to 48)
      were enrolled. Average time from injury to reconstruction was 8 weeks. The
      patients' contralateral knee served as an internal control, and 26 age-matched
      and gender-matched healthy volunteers were enrolled as an external control group.
      ACL reconstructions were performed using a single-incision technique with either
      bone-patellar tendon-bone or quadrupled hamstring autograft. They were allowed
      immediate weightbearing as tolerated and participated in a standardized
      rehabilitation program, with the goal of returning to sport at approximately 6
      months. Proprioception testing was carried out using an electrogoniometer, in a
      seated position. Joint position sense (JPS) and threshold to detection of passive
      motion (TDPM) were measured preoperatively and at 3 and 6 weeks and 3 and 6
      months postoperatively. RESULTS: Mean KT-2000 values 6 months postoperatively
      were 1.38 mm (+/-2). Modified Lysholm score improved significantly (P <.01).
      Calculated r values were 0.65 for JPS and 0.96 for TDPM. No significant
      differences in postoperative proprioception were found between hamstring and
      patellar tendon grafts or among patients with meniscus injury, meniscus repair,
      or chondral injury. Preoperatively, the mean TDPM in both the injured and
      contralateral knees was significantly higher (worse) than in the external control
      knees (P =.008; P =.016). Evaluation of changes in proprioception from
      preoperative to 6 months postoperative showed significant improvement in both
      injured and contralateral knees (P =.04; P =.01). At 6-month follow-up, there was
      no significant difference from controls. CONCLUSIONS: TDPM was a more reliable
      method than JPS for testing proprioception before and after ACL reconstruction in
      this study. Bilateral deficits in knee joint proprioception (TDPM) were
      documented after unilateral ACL injury. Reconstruction of a mechanical restraint
      (ACL graft) was believed to have a significantly positive impact on early and
      progressive improvement in proprioception.

PMID- 12522395
TI  - Arthroscopic treatment for synovial chondromatosis of the shoulder.
AB  - Synovial chondromatosis of the shoulder is a rare condition. The following is a
      description of such a case with the presenting symptoms, radiographic features,
      intraoperative findings, and the arthroscopic technique for treatment of this
      disease. Loose bodies were found in the long head of the biceps tendon sheath,
      the subscapularis recess, and throughout the glenohumeral joint, causing erosive
      damage. We feel that arthroscopy allows for better visualization of the entire
      glenohumeral joint, including the long head of the biceps tendon sheath and the
      subscapularis recess, and for ease of loose body removal. Additional advantages
      of arthroscopy include decreased postoperative pain, early active range of
      motion, shorter course of rehabilitation, and earlier functional return.

PMID- 12522396
TI  - A modified bone-tendon-bone harvesting technique for avoiding tibial tunnel-graft
      mismatch in anterior cruciate ligament reconstruction.
AB  - Anatomic graft fixation in anterior cruciate ligament reconstruction has been
      shown to be extremely important for achieving acceptable postoperative knee
      stability. Different methods have been proposed for customizing graft length, so
      that anatomic graft fixation is obtained at the native anterior cruciate ligament
      site. A technique has been described for avoiding potential complications during
      the insertion of an interference screw at femoral tunnel and, ultimately,
      reducing the mismatch within the femoral tunnel. The aim of this article is to
      present a modified application to the tibial tunnel of a previously described
      technique for avoiding graft-tunnel mismatch. The advantages are related to the
      increase in graft complex stiffness, achievement of a more anatomic fixation, and
      the reduction in synovial fluid leakage.

PMID- 12522397
TI  - Endoscopic treatment of calcific tendinitis of gluteus medius and minimus.
AB  - Calcific tendinitis results from deposition of calcium hydroxyapatite crystals in
      periarticular muscle attachments. Although involvement of tendons around the hip
      is not uncommon, gluteus medius and minimus tendons are rarely affected. We
      present endoscopic treatment of calcific tendonitis of gluteus medius and minimus
      and associated trochanteric bursitis in a patient with 2-year history of lateral
      hip pain. This is the first reported case treated using an endoscopic approach,
      which is effective and minimally invasive.

PMID- 12522398
TI  - The results of arthroscopic lavage and debridement of osteoarthritic knees based
      on the severity of degeneration: a 4- to 6-year symptomatic follow-up.
AB  - PURPOSE: A clinically and arthroscopically oriented staging system based on the
      severity of the degenerative process has been used in the assessment of the
      results of arthroscopic lavage and debridement of osteoarthritic (OA) knees. TYPE
      OF STUDY: Retrospective case series. METHODS: For eighteen months, commencing
      January 1995, every case of previously untreated OA referred for definitive
      treatment was clinically classified into 1 of 4 stages of increasing
      degeneration. Excluded were patients who were treated nonoperatively, by
      replacement arthroplasty or marrow stimulation techniques. A group of 121 cases
      treated by arthroscopic lavage and debridement were available for review with a 4
      to 6 year follow-up. RESULTS: Arthroscopic lavage and debridement carried out in
      the earlier stages of the degenerative process resulted in significant relief of
      symptoms for reasonably long periods of time. The more advanced stages of
      degeneration commonly experienced some temporary relief from arthroscopic lavage
      and debridement, but the amount of improvement was unpredictable. CONCLUSIONS:
      The surgeon's armamentarium for the treatment of degenerative arthritis
      unresponsive to conservative treatment methods should involve minimal
      interventional arthroscopy at an earlier, rather than a later stage in the
      disease process. It is recommended that the arthroscopist be conservative in the
      surgical debridement, removing only the fibrillated and scaling fragments of
      articular cartilage.

PMID- 12522399
TI  - Arthroscopic repair of anterosuperior (supraspinatus/subscapularis) rotator cuff
      tears: a prospective cohort with 2- to 4-year follow-up. Classification of biceps
      subluxation/instability.
AB  - PURPOSE: The purpose of this study was to evaluate the outcome of patients who
      underwent arthroscopic repair of anterosuperior rotator cuff tears. The null
      hypothesis, that there was no difference between preoperative scores and
      postoperative scores, was tested statistically. TYPE OF STUDY: A cohort study.
      METHODS: The preoperative and postoperative status of patients with
      anterosuperior rotator cuff tears was analyzed using the Constant score, American
      Shoulder and Elbow Society Index (ASES Index), a visual analog pain scale (VAS),
      a single question of percent function compared with the opposite unaffected
      extremity, and a single question reflecting satisfaction, "would you undergo the
      surgery and the postoperative rehabilitation to achieve the result you have
      today." There were also 2 groups compared: 1 that had a "tac" used for repair of
      the subscapularis tendon, and the other that used a "tie" technique for
      subscapularis repair. All supraspinatus tendon tears were complete and were
      repaired using a soft-tissue fixation device. RESULTS: There was a statistically
      significant difference for all outcome measures except for the objective Constant
      score of the tie group, P =.58. Follow-up was 2 to 4 years. There were no
      differences based on sex or type of fixation device used for repair of the
      subscapularis tendon. There were no reruptures, clinically. CONCLUSIONS: The
      arthroscopic repair of anterosuperior rotator cuff tears provides reliable
      expectation for improvement in function, decreases in pain, decreases in clinical
      findings of biceps subluxation and inflammation, improvement in shoulder scores,
      and the improvement of clinical findings of subscapularis insufficiency.

PMID- 12522400
TI  - The relationship between clinical outcomes and the amount of arthroscopic
      acromial resection.
AB  - PURPOSE: In 47 consecutive patients who had a shoulder impingement syndrome
      treated by arthroscopic subacromial decompression, we compared the functional
      outcome with the amount of the acromion resection. TYPE OF STUDY: Prospective
      study. METHODS: The inclusion criteria for patient selection was a chronic
      impingement syndrome unresolved by conservative treatment with an intact rotator
      cuff or with an irreparable rupture of the rotator cuff. The assessment was
      performed with the scoring system of Constant preoperatively and postoperatively.
      Quantitative measurements of the acromion resection were made by comparing
      preoperative and postoperative anteroposterior radiographic views, standardized
      under fluoroscopic control in order to become reproducible and comparable. There
      were 39 patients (41 shoulders) available for follow-up at 37 months. RESULTS:
      The condition of the shoulder, concerning pain, motion and activities, was
      improved at the time of follow-up, the mean gain of the total functional score
      was 29 points/100. Age, side, activity, duration of pain before procedure and
      cuff statement had no influence on preoperative and postoperative Constant's
      score. The difference between preoperative and postoperative measurements of
      anterior acromion protuberance was significant. There was no correlation between
      the amount of the acromion resection and the improvement of Constant's score (P
      =.84). CONCLUSIONS: The origin of impingement syndrome is multi-factorial, and
      efficiency of arthroscopic decompression may not be only due to the amount of
      acromion resection. From these results and a literature review, this study
      analyzes several morphologic factors, which could explain the good results of
      arthroscopic subacromial decompression in impingement syndrome.

PMID- 12522401
TI  - Arthroscopic capsular release for stiff shoulders: effect of etiology on
      outcomes.
AB  - PURPOSE: The etiology, pathogenesis, time course, and response to treatment of
      stiff shoulder pathology is still under investigation and debate. This
      prospective study evaluated arthroscopic capsular release to treat stiff shoulder
      pathology that was resistant to conservative management. The etiology of the
      shoulder stiffness was categorized and analyzed for effect on outcomes. TYPE OF
      STUDY: Operative technique and prospective evaluation. METHODS: In 68 stiff
      shoulders (41 in women, 27 in men) that underwent arthroscopic capsular release,
      5 distinct etiologies were identified: postsurgical in 20, idiopathic in 17, post
      traumatic in 15, diabetic in 8, and impingement syndrome (prior primary
      impingement developing stiffness) in 8. Average age was 50 years (range, 29 to
      72), and follow-up averaged 3 years (range, 2 to 8). Prior to this procedure,
      duration of symptoms averaged 7.3 months (range, 3 to 48), and formal physical
      therapy averaged 3.7 months (range, 1 to 12). Preoperative average American
      Shoulder and Elbow Surgeons Score (ASES) was 35.5 (range, 10 to 77), median
      Simple Shoulder Test (SST) was 3 (0 to 10), and median Visual Analog Score (VAS)
      for pain was 6 (0 to 10). Average active forward elevation (FE) was 92 degrees,
      external rotation (ER) at side was 12 degrees, and median internal rotation (IR)
      was to the buttock. All patients underwent arthroscopic capsular release with a
      standard aftercare protocol. RESULTS: The study population showed significant
      improvement (P <.0001) for all outcome scores and active motion parameters.
      Average and median outcome parameters for the population, with improvement in
      parenthesis were: ASES 93 (+57.5), SST 10 (+7), VAS 0 (-6), FE 165 degrees (+73
      degrees ), ER at side 56 degrees (+44 degrees ), and IR to T -12 (+7 spinal
      segments). The time in formal physical therapy averaged 2.3 months (2 to 20
      weeks) and time to attain final, pain-free range of motion averaged 2.8 months (1
      to 6). Outcomes for, and between, each etiology were analyzed. There was no
      difference in time to final motion between the etiologic groups. CONCLUSIONS:
      Stiff shoulder pathology can result from a variety of differing etiologic
      factors. Arthroscopic capsular release was equally effective across the 5
      identified etiologic groups, and provided significant pain relief, restoration of
      motion, and function within an average of 3 months.

PMID- 12522402
TI  - A randomized, double-blind trial of pre-emptive local anesthesia in day-case knee
      arthroscopy.
AB  - PURPOSE: The study goal was to assess the efficacy of pre-emptive analgesia in a
      clinical setting. TYPE OF STUDY: A block randomized, double-blind design was
      used. METHODS: Subjects were 40 patients undergoing day-case arthroscopy of the
      knee. The trial group received a prophylactic injection of bupivacaine with
      adrenaline. After surgery, a placebo injection was given. The postsurgical
      injection group received identical injections in reverse order. There was no
      difference in the mean dose of propofol used to maintain general anesthesia
      between groups: 15 mg/kg/h (standard deviation [SD] = 2.85) trial versus 14.6
      mg/kg/h (SD = 1.96) postsurgical injection (95% confidence interval [CI] = -1.14
      to 1.94). RESULTS: Although no statistically significant difference was observed
      in postoperative pain scores at 15, 30, or 60 minutes, there was a trend for the
      trial group to require less analgesia in recovery (chi2 = 9.74; P =.1).
      CONCLUSIONS: Prophylactic local anesthesia confers no statistically significant
      reduction in pain scores or perioperative general anesthetic requirements as
      compared with postoperative administration. The pre-emptive effect in clinical
      practice may be less dramatic than that observed in more controlled animal
      models. Further studies are required to investigate the magnitude of the pre
      emptive effect in clinical practice.

PMID- 12522403
TI  - Anterograde arthroscopic fixation of avulsion fractures of the tibial eminence
      with a cannulated screw: five-year results.
AB  - PURPOSE: Fractures of the tibial eminence can be treated arthroscopically.
      Fixation of the fracture is usually followed by temporary immobilization. The
      literature suggests that only anterograde fixation with cannulated screws and
      washer is considered stable enough to allow for immediate mobilization and weight
      bearing. The goal of this study was to evaluate the 5-year results of
      arthroscopic reductions and anterograde fixations of the tibial eminence fracture
      with cannulated screws. TYPE OF STUDY: Retrospective study. METHODS: Thirty-two
      patients were treated arthroscopically for type II, III, and IV fractures of the
      intercondylar eminence of the tibia. The fragments were reduced and fixed with a
      cannulated screw or cannulated screw and washer. The intermeniscal ligament was
      involved in the fracture in 29 cases, and the anterior part of the medial
      meniscus was involved in 3 cases, requiring a temporary shift before reduction of
      the fragment. Arthrotomy was not performed for reduction or fixation of the
      fragment. All patients began continuous passive and active motion of the involved
      knee and were mobilized on crutches the day after the procedure. They were
      allowed immediate weight bearing. The patients were followed up for 16 to 69
      months. RESULTS: Good therapeutic results were found at follow-up. Average value
      for KT-1000 testing was 1.1 mm; flexion deficit was 1.2 degrees; extension
      deficit, 0.6 degrees; and Lysholm score, 98.8. The average treatment duration was
      12 weeks. There was one case of aseptic synovitis and no other complications. In
      all but 1 patient, the implants were removed. CONCLUSIONS: Arthroscopic fixation
      of the fracture of the intercondylar eminence of the tibia with a cannulated
      screw or screw and washer is a simple, safe, reproducible, and effective
      procedure. The fixation is stable even in type IV fractures, so that
      immobilization is unnecessary.

PMID- 12522404
TI  - Posterior arthroscopic approach to the ankle: an anatomic study.
AB  - PURPOSE: The purpose of this study is to verify the safety of a new technique for
      a posterior arthroscopic approach to the ankle. This technique was recently
      described in literature. The technique uses a modified posteromedial portal, a
      different way of introducing the instruments into the portal, and the tendon of
      the flexor hallucis longus (FHL) as a landmark to work in the posterior
      compartment. TYPE OF STUDY: Anatomic study. METHODS: The technique was performed
      on 10 (4 fresh and 6 fresh-frozen) below-knee amputation specimens, which were
      then dissected. The instruments were left in place, and anatomic dissections were
      performed to determine the relationship to the surrounding neurovascular
      structures. Then the instruments were removed, and the distance of the
      neurovascular structures from the posteromedial portal was recorded. Another
      medial portal, 1 cm more proximal, was also created to measure the distance of
      this latter portal from the nervous structures. RESULTS: None of the anatomic
      dissections showed injuries to the neurovascular bundle either during penetration
      of the instruments or during procedures in the posterior compartment laterally to
      the tendon of the FHL. This latter is the landmark to prevent damage to the more
      medially located nerves and vessels. The new posteromedial portal is located, on
      average, 13.3 mm (range, 11 to 17 mm) from the posterior tibial nerve, 14.7 mm
      (range, 8 to 20) from the calcaneal branch (which may be single or multiple, and
      may vary as needed the height of bifurcation from the posterior tibial nerve),
      and 17.3 mm (range, 15 to 21 mm) from the posterior tibial artery. A
      posteromedial portal located 1 cm more proximally is on average 2.9 mm closer to
      the nervous structures. CONCLUSIONS: Based on these anatomic data, there appears
      to be relatively little risk to the surrounding neurovascular structures with
      this new technique. Therefore, this technique appears to be relatively safe in
      the treatment of intra-articular and extra-articular pathology.

PMID- 12522405
TI  - Implantation sites and fiber diameters affect the rate of degradation in
      absorbable polydioxanone fibers.
AB  - PURPOSE: The purpose of this study is to test the question of whether
      implantation sites and fiber diameters affect the rate of degradation in
      absorbable polydioxanone fibers. TYPE OF STUDY: Randomized trial. METHODS: Forty
      eight mature rabbits were used. In the first study, using 24 rabbits, a 0.3-mm
      diameter polydioxanone fiber was implanted into the subcutaneous, intra
      articular, and intramedullary sites. Six rabbits each were killed at 1, 2, 3, and
      6 weeks after surgery. In the second study, the remaining 24 rabbits were divided
      into 2 groups of 12 animals each. In group I, a 0.3-mm diameter fiber was
      implanted into the intramedullary and subcutaneous sites. In group II, a 0.6-mm
      diameter fiber was implanted in the same manner. In each group, 6 rabbits were
      killed at 3 and 6 weeks. In each study, all fiber specimens underwent tensile
      testing to determine the material properties. We defined the percentage of the
      maximum load of each fiber specimen compared with the normal control value as the
      I/N ratio. RESULTS: In the first study, the maximum load and the stiffness of the
      fibers implanted into the intramedullary site were significantly lower than those
      of the fibers implanted into the other 2 sites at each period (P <.0001). In the
      second study, the I/N ratio of group I was significantly less than that of group
      II at each implanted site (P <.0001). CONCLUSIONS: Polydioxanone fiber implanted
      into the intramedullary site deteriorates more rapidly than that implanted into
      the subcutaneous and the intra-articular sites. Thin fibers deteriorate more
      rapidly than thick fibers. Therefore, the degradation of absorbable synthetic
      fibers intended for use in ligament reconstruction should be evaluated not only
      in the subcutaneous site but also in the intramedullary site using various
      diameter fibers.

PMID- 12522406
TI  - The skier's knee.
AB  - Knee injuries in skiers have unique epidemiology and distinct mechanisms.
      Conversely, evaluation and treatment of the skier's knee is similar to evaluation
      and treatment of knee injuries in other athletes. A greater understanding of the
      epidemiology and mechanisms of knee injuries in skiers may aid arthroscopic
      clinicians and related researchers treating or investigating knee injuries in
      both skiers and in other athletes.

PMID- 12522407
TI  - Arthroscopic treatment of gunshot wounds to the shoulder.
AB  - Two cases are presented that demonstrate the utility of arthroscopic intervention
      for the management of gunshot wounds to the shoulder. The first report involves a
      24-year-old man with a retained bullet in his glenohumeral joint after a drive-by
      shooting The intra-articular bullet was retrieved arthroscopically avoiding
      chondral injury from the mechanical effects of a loose body as well as the
      potential local and systemic effects of lead toxicity. Irrigation and debridement
      was performed to evacuate joint debris, which could have served as a nidus for
      infection or inflammation. The other case describes a 19-year-old man who
      sustained a gunshot wound to the lateral portion of his upper arm resulting in a
      proximal humerus fracture along with a retained bullet in his subacromial space.
      The bullet was successfully removed arthroscopically avoiding a traditional
      exposure, which would have complicated his fracture care.

PMID- 12522408
TI  - Anteromedial meniscofemoral ligament.
AB  - We have experienced 3 cases of comparatively rare anteromedial meniscofemoral
      ligament in which the anterior horn of the medial meniscus was attached to the
      posterolateral wall of the femoral intercondylar fossa. In 2 of these cases,
      there was no attachment to the tibia, whereas in the other, it was connected to
      the lateral meniscus and also firmly to the tibia. In the 2 with no attachment to
      the tibia, abnormal mobility in the medial meniscus accompanied by flexion and
      extension of the knee was observed. Degeneration of the intermediate posterior
      segment and injury of the anterior horn were also observed. This anomaly induces
      a future meniscus injury, depending on the attachment state to the tibia.

PMID- 12522409
TI  - Treatment of a large intraosseous talar ganglion by means of hindfoot endoscopy.
AB  - We report on 2 patients with a large intraosseous ganglion of the talus who were
      treated by means of a 2-portal endoscopic approach of the hindfoot with the
      patient in the prone position. By means of this approach, it is possible to
      visualize, debride, and graft a large intraosseous talar lesion. In both
      patients, the lesions were treated successfully, with no recurrence at follow up.

PMID- 12522410
TI  - Arthroscopic posterior cruciate ligament reconstruction using the posterior trans
      septal portal.
AB  - We describe an arthroscopic technique for the reconstruction of the posterior
      cruciate ligament (PCL), while preserving the remnant bundle of the original PCL
      and meniscofemoral ligament, using the posterior trans-septal portal. The
      posterior trans-septal portal provides an excellent visualization of the PCL
      tibial attachment and an easy access to the tibial tunnel without injuring any
      neurovascular structure. The remnant bundle of the original PCL and
      meniscofemoral ligament, which significantly contributes to the posterior
      stability of the knee joint, are preserved to be healed with a graft and
      subsequently form an integrated structure. We report a new arthroscopic technique
      for an effective reconstruction of the PCL, using the posterior trans-septal
      portal.

PMID- 12522411
TI  - The arthroscopic implantation of autologous chondrocytes for the treatment of
      full-thickness cartilage defects of the knee joint.
AB  - Autologous chondrocyte implantation is an established option for the treatment of
      full-thickness cartilage defects of the knee. Open implantation has a high
      morbidity. On a resorbable polymer fleece, autologous chondrocytes can be
      implanted arthroscopically. Transosseous anchoring assures high initial stability
      of the implant. Tibial defects can be addressed. The arthroscopic technique for
      the implantation of autologous chondrocytes eliminates a substantial amount of
      the side effects known to occur after open autologous chondrocyte implantation
      procedures.

PMID- 12522412
TI  - Tendon healing in a bone tunnel. Parts I and II.

PMID- 12522414
TI  - Comparative genomics. Population genomics: celebrating individual expression.

PMID- 12522415
TI  - Comparative genomics. Plant genomes: cyanobacterial genes revealed.

PMID- 12522416
TI  - Evolution and development. Making jaws.

PMID- 12522420
TI  - Hybridization of banteng (Bos javanicus) and zebu (Bos indicus) revealed by
      mitochondrial DNA, satellite DNA, AFLP and microsatellites.
AB  - Hybridization between wild and domestic bovine species occurs worldwide either
      spontaneously or by organized crossing. We have analysed hybridization of banteng
      (Bos javanicus) and zebu (Bos indicus) in south-east Asian cattle using
      mitochondrial DNA (PCR-RFLP and sequencing), AFLP, satellite fragment length
      polymorphisms (SFLP or PCR-RFLP of satellite DNA) and microsatellite genotyping.
      The Indonesian Madura zebu breed is reputed to be of hybrid zebu-banteng origin,
      but this has never been documented and Bali cattle are considered to be a
      domesticated form of banteng. The banteng mitochondrial type was found in all
      animals sampled on the isle of Bali, Indonesia, but only in 35% of the animals
      from a Malaysian Bali-cattle population. The Madura animals also carried
      mitochondrial DNA of either zebu and banteng origin. In both populations, zebu
      introgression was confirmed by AFLP and SFLP. Microsatellite analysis of the
      Malaysian Bali population revealed for 12 out of 15 loci screened, Bali-cattle
      specific alleles, several of which were also found in wild banteng animals. The
      tools we have described are suitable for the detection of species in
      introgression studies, which are essential for the genetic description of local
      breeds and the preservation of their economic and cultural value.

PMID- 12522421
TI  - Combined use of maternal, paternal and bi-parental genetic markers for the
      identification of wolf-dog hybrids.
AB  - The identification of hybrids is often a subject of primary concern for the
      development of conservation and management strategies, but can be difficult when
      the hybridizing species are closely related and do not possess diagnostic genetic
      markers. However, the combined use of mitochondrial DNA (mtDNA), autosomal and Y
      chromosome genetic markers may allow the identification of hybrids and of the
      direction of hybridization. We used these three types of markers to genetically
      characterize one possible wolf-dog hybrid in the endangered Scandinavian wolf
      population. We first characterized the variability of mtDNA and Y chromosome
      markers in Scandinavian wolves as well as in neighboring wolf populations and in
      dogs. While the mtDNA data suggested that the target sample could correspond to a
      wolf, its Y chromosome type had not been observed before in Scandinavian wolves.
      We compared the genotype of the target sample at 18 autosomal microsatellite
      markers with those expected in pure specimens and in hybrids using assignment
      tests. The combined results led to the conclusion that the animal was a hybrid
      between a Scandinavian female wolf and a male dog. This finding confirms that
      inter-specific hybridization between wolves and dogs can occur in natural wolf
      populations. A possible correlation between hybridization and wolf population
      density and disturbance deserves further research.

PMID- 12522422
TI  - Genetic and clonal diversity for Myrica cerifera along a spatiotemporal island
      chronosequence.
AB  - Changes in genetic diversity and clonal structure were investigated along a
      spatiotemporal island chronosequence for the shrub Myrica cerifera. On our study
      site, Hog Island, Virginia, USA, island movement creates a sequence of dune
      ridges and intervening swales along an east-west axis of the island that produces
      an age-structured geomorphology. This substrate-mediated age structure, called
      the chronosequence, superimposes itself upon cohorts of M. cerifera that colonize
      behind nascent dune ridges as they are formed. This chronosequence allowed
      comparisons of levels of genetic diversity and clonal structure among different
      aged cohorts of M. cerifera. We observed little change in allelic diversity along
      the chronosequence and no evidence for heterosis, although there was moderate
      change in genotypic diversity. The spatial distribution of individuals within 10
      plots established along three transects intersecting the island chronosequence
      identified a nonrandom spatial distribution of individuals in all cohorts, with
      increasing aggregation of above-ground stems into multistemmed clusters in the
      older sites. This aggregation of individuals did not correspond to a significant
      increase in clonal growth with cohort age, nor was there significant spatial
      genetic autocorrelation within any of the plots.

PMID- 12522423
TI  - Effects of genotyping errors, missing values and segregation distortion in
      molecular marker data on the construction of linkage maps.
AB  - A simulation study was performed to investigate the effects of missing values,
      typing errors and distorted segregation ratios in molecular marker data on the
      construction of genetic linkage maps, and to compare the performance of three
      locus-ordering criteria (weighted least squares, maximum likelihood and minimum
      sum of adjacent recombination fractions criteria) in the presence of such
      effects. The study was based upon three linkage groups of 10 loci at 2, 6, and 10
      cM spacings simulated from a doubled-haploid population of size 150. Criteria
      performance were assessed using the number of replicates with correctly estimated
      orders, the mean rank correlation between the estimated and the true order and
      the mean total map length. Bootstrap samples from replicates in the maximum
      likelihood analysis produced a measure of confidence in the estimated locus
      order. The effects of missing values and/or typing errors in the data are to
      reduce the proportion of correctly ordered maps, and this problem worsens as the
      distances between loci decreases. The maximum likelihood criterion is most
      successful at ordering loci correctly, but gives estimated map lengths, which are
      substantially inflated when typing errors are present. The presence of missing
      values in the data produces shorter map lengths for more widely spaced markers,
      especially under the weighted least-squares criterion. Overall, the presence of
      segregation distortion has little effect on this population.

PMID- 12522424
TI  - QTL analysis of an intervarietal set of substitution lines in Brassica napus: (i)
      Seed oil content and fatty acid composition.
AB  - Backcross breeding with marker-assisted selection was used to construct an
      intervarietal set of part chromosome substitution lines in Brassica napus, formed
      from a cross between two winter varieties of oilseed rape: Tapidor and Victor. A
      total of 22 lines from this substitution library were examined over a 3-year
      period, in a total of nine field trials, for seed oil fatty acid composition and
      seed oil content. Trialing of the substitution lines gave evidence for the
      existence of 13 quantitative trait loci (QTL). All 13 QTL affected fatty acid
      composition of the seed, and were distributed among linkage groups 1, 3, 6, 7, 8,
      11, 13, 14, 18, and 19. Seven of these QTL, on linkage groups 3, 6, 8, 13, 14,
      18, and 19, also affected total seed oil content. The positions of these QTL are
      compared to those in the published literature and with respect to erucic acid QTL
      previously identified in a backcross population of the same cross. The
      substitution line approach gives increased precision and sensitivity for QTL
      mapping compared to other methods.

PMID- 12522425
TI  - Characterization of non-cytoplasmic incompatibility inducing Wolbachia in two
      continental African populations of Drosophila simulans.
AB  - Wolbachia is an endocellular bacterium infecting arthropods and nematodes. In
      arthropods, it invades host populations through various mechanisms, affecting
      host reproduction, the most common of which being cytoplasmic incompatibility
      (CI). CI is an embryonic mortality occurring when infected males mate with
      uninfected females or females infected by a different Wolbachia strain. This
      phenomenon is observed in Drosophila simulans, an intensively studied Wolbachia
      host, harbouring at least five distinct bacterial strains. In this study, we
      investigate various aspects of the Wolbachia infections occurring in two
      continental African populations of D. simulans: CI phenotype, phylogenetic
      position based on the wsp gene and associated mitochondrial haplotype. From the
      East African population (Tanzania), we show that (i) the siIII mitochondrial
      haplotype occurs in continental populations, which was unexpected based on the
      current views of D. simulans biogeography, (ii) the wKi strain (that rescues from
      CI while being unable to induce it) is very closely related to the CI-inducing
      strain wNo, (iii) wKi and wNo might not derive from a unique infection event, and
      (iv) wKi is likely to represent the same entity as the previously described wMa
      variant. In the West African population (Cameroon), the Wolbachia infection was
      found identical to the previously described wAu, which does not induce CI. This
      finding supports the view that wAu might be an ancient infection in D. simulans.

PMID- 12522426
TI  - Segregation analysis of heading traits in hexaploid wheat utilizing recombinant
      inbred lines.
AB  - The purpose of this study was to analyze the genetic segregation of heading
      traits in wheat using recombinant inbred lines (RILs) of hexaploid wheat, derived
      from Triticum aestivum cv. Chinese Spring and T. spelta var. duhameliamum. The
      population was examined under controlled environmental conditions as well as in
      the field. This strategy differentiated the effect of three genetic factors
      (vernalization requirement, photoperiod sensitivity and narrow-sense earliness)
      and identified their interactions. Correlation analysis showed that photoperiod
      sensitivity and narrow-sense earliness are critical for heading time in the
      field. Single-marker analysis using 322 molecular markers segregating among RIL
      detected a total of 38 linked markers for each genetic factor and heading in the
      field. In interval analysis, two Vrn genes (Vrn-B1 and Vrn-D1) and Ppd-B1 were
      mapped on chromosomes 5B, 5D and 2B, respectively. It was noticed that Vrn-B1 on
      5B from the spelt wheat conferred a strong-spring habit equivalent to the
      homologous Vrn-A1. Quantitative trait locus analysis also showed that Ppd-B1 was
      not detected under the short-day condition without vernalization treatment, and
      that there were two types of genes for photoperiod sensitivity, dependent on and
      independent of vernalization treatment.

PMID- 12522427
TI  - Population structure in the freshwater shrimp (Paratya australiensis) inferred
      from allozymes and mitochondrial DNA.
AB  - In 1995, an allozyme study was conducted on the genetic structure of a population
      of the common atyid shrimp, Paratya australiensis, in the Conondale Range, south
      eastern Queensland with two subcatchments each within two river drainages
      sampled. The allozyme study revealed a high degree of population structure, with
      the data interpreted as reflecting a pattern of restricted contemporary gene
      flow, primarily between streams within subcatchments. High levels of
      differentiation occurred between all subcatchments. In this study, we analysed a
      partial fragment of the mitochondrial COI gene in order to further test and
      verify these results. The mtDNA data largely conflicted with the hypothesis of
      restricted gene flow indicating that contemporary dispersal was highly unlikely,
      even between streams within subcatchments, with many sites fixed for unique mtDNA
      haplotypes. Additionally, the level of divergence between the Stony Creek
      subcatchment and all other sampling sites indicated that it had been isolated for
      approximately 2-3 million years, while low levels of divergence were detected
      across the Conondale Range between the Kilcoy and Booloumba Creek subcatchments.
      The sharing of alleles at certain allozyme loci between all subcatchments is,
      therefore, likely to be the result of ancestral retention and possibly because of
      the effects of balancing selection.

PMID- 12522428
TI  - Superinfection of Laodelphax striatellus with Wolbachia from Drosophila simulans.
AB  - Wolbachia are maternally inherited, intracellular alpha-proteobacteria that
      infect a wide range of arthropods. They manipulate the reproduction of hosts to
      facilitate their spread into host populations, through ways such as cytoplasmic
      incompatibility (CI), parthenogenesis, feminization and male killing. The
      influence of Wolbachia infection on host populations has attracted considerable
      interest in their possible role in speciation and as a potential agent of
      biological control. In this study, we used both microinjection and nested PCR to
      show that the Wolbachia naturally infecting Drosophila simulans can be
      transferred into a naturally Wolbachia-infected strain of the small brown
      planthopper Laodelphax striatellus, with up to 30% superinfection frequency in
      the F(12) generation. The superinfected males of L. striatellus showed
      unidirectional CI when mated with the original single-infected females, while
      superinfected females of L. striatellus were compatible with superinfected or
      single-infected males. These results are, to our knowledge, the first to
      establish a superinfected horizontal transfer route for Wolbachia between
      phylogenetically distant insects. The segregation of Wolbachia from superinfected
      L. striatellus was observed during the spreading process, which suggests that
      Wolbachia could adapt to a phylogenetically distant host with increased infection
      frequency in the new host population; however, it would take a long time to
      establish a high-frequency superinfection line. This study implies a novel way to
      generate insect lines capable of driving desired genes into Wolbachia-infected
      populations to start population replacement.

PMID- 12522429
TI  - Inbreeding and the genetic variance in floral traits of Mimulus guttatus.
AB  - The additive genetic variance, V(A), is frequently used as a measure of
      evolutionary potential in natural plant populations. Many plants inbreed to some
      extent; a notable observation given that random mating is essential to the model
      that predicts evolutionary change from V(A). With inbreeding, V(A) is not the
      only relevant component of genetic variation. Several nonadditive components
      emerge from the combined effects of inbreeding and genetic dominance. An
      important empirical question is whether these components are quantitatively
      significant. We use maximum likelihood estimation to extract estimates for V(A)
      and the nonadditive 'inbreeding components' from an experimental study of the
      wildflower Mimulus guttatus. The inbreeding components contribute significantly
      to four of five floral traits, including several measures of flower size and
      stigma-anther separation. These results indicate that inbreeding will
      substantially alter the evolutionary response to natural selection on floral
      characters.

PMID- 12522430
TI  - Genetic dimension of the coevolution of virulence-resistance in Drosophila --
      parasitoid wasp relationships.
AB  - Variations observed in parasite virulence and host resistance may be the outcome
      of coevolutionary processes. Recent theoretical developments have led to a
      'geographic mosaic theory' of coevolution according to which there are some
      localities where reciprocal selection occurs (hot spots) and others where it is
      strongly reduced (cold spots). Studies of host-parasitoid systems back this up,
      revealing a geographical variation of traits subjected to antagonistic selection
      governed by variations in the strength of the ecological interactions. A more
      detailed analysis of the genetic basis of these geographic variations in a model
      system -- the interaction between Drosophila melanogaster and its specific
      parasitoid Leptopilina boulardi -- suggests that cold spots and hot spots are
      also driven by the amount of genetic variation available for the trait
      considered. Our approach, based on isolating reference strains, has been found to
      predict the result of sympatric interactions and it will be helpful in
      identifying the selective forces responsible for the coevolution. In this model,
      host resistance to a standardised reference strain is a weak predictor of the
      outcome of interactions in the field, and the main parameter accounting for the
      geographic variations is the number of host species available, with less
      parasitoid virulence towards D. melanogaster being found in areas displaying a
      more diversified host community.

PMID- 12522431
TI  - Contrasting patterns of genetic variation in the two sympatric geckos Gekko
      tawaensis and G. japonicus (Reptilia: Squamata) from western Japan, as revealed
      by allozyme analyses.
AB  - Allozyme variation in two congeneric sympatric geckos, Gekko tawaensis and G.
      japonicus, from western Japan was examined. These species show similar densities
      and spatial arrangements of populations in this region, and their genetic
      structures are thus expected to have been formed under the influences of
      comparable geohistorical, environmental, and demographic factors. Results of the
      analyses, however, revealed strikingly different genetic patterns in the two
      species. Populations of G. tawaensis invariably showed a remarkably lowered
      heterozygosity (0-0.017) compared to G. japonicus (0.089-0.124). On the other
      hand, the genetic heterogeneity among populations is much greater in G. tawaensis
      (F(ST)=0.726) than in G. japonicus (F(ST)=0.101). The Mantel test failed to
      detect any significant correlations between log (estimated migration rate) and
      log (geographic distance) in either species, or between matrices of
      interpopulation pairwise F(ST) for the two species. These results suggest that,
      in each species, formation of the current genetic structure in western Japan has
      been chiefly influenced by stochastic factors, rather than the geohistorical
      architecture of this region. The high F(ST) and low heterozygosity in G.
      tawaensis suggest the effects of severe local fragmentation. On the other hand,
      the relatively low F(ST) and high heterozygosity in G. japonicus imply extensive
      gene flow among populations. Absence of significant correlations between the
      estimated migration rate and geographic distance in G. japonicus may suggest that
      such gene flow is promoted by human-mediated transport of this primarily house
      dwelling lizard.

PMID- 12522432
TI  - Temporal aspects of the fine-scale genetic structure in a population of
      Cinnamomum insularimontanum (Lauraceae).
AB  - Cinnamomum insularimontanum Hayata (Lauraceae) is an insect-pollinated, broad
      leaved evergreen tree with bird-dispersed seeds. We used allozyme loci, Wright's
      fixation index, spatial autocorrelation statistics (Moran's I), and coancestry
      measures to examine changes in genetic structure among four age-classes within a
      recently founded study population (60 x 100 m area) in southern Korea. There were
      no significant differences in expected heterozygosity among age classes. However,
      significant genetic differentiation among age classes was detected (P<0.0001).
      Fixation indices within age classes showed significant deficits of observed
      heterozygosity, which may be caused by partial selfing. The homogeneity of
      genetic structure among four age-classes may reflect similar spatial patterns of
      seed immigration from surrounding populations occurring year after year. Finally,
      the average Moran's I and coancestry estimates indicated essentially random
      spatial distributions of alleles for each of the four age-classes and between
      seedlings and 2-4 year juveniles vs adult trees. These findings are very similar
      to those observed in the same study area for another member of the Lauraceae,
      Neolitsea sericea, which has a very similar life history and ecological
      characteristics (ie, bird-dispersed fruits, insect pollination, and a similar age
      structure). Together, these results suggest that the fleshy drupes of lauraceous
      species represent an adaptation to aid in the independent dispersal of seed by
      birds, which in turn may increase the genetic diversity of founders colonizing
      new habitats.

PMID- 12522433
TI  - Constraints on adaptive mutations in the codling moth Cydia pomonella (L.):
      measuring fitness trade-offs and natural selection.
AB  - Adaptive changes in populations encountering a new environment are often
      constrained by deleterious pleiotropic interactions with ancestral physiological
      functions. Evolutionary responses of populations can thus be limited by natural
      selection under fluctuating environmental conditions, if the adaptive mutations
      are associated with pleiotropic fitness costs. In this context, we have followed
      the evolution of the frequencies of insecticide-resistant mutants of Cydia
      pomonella when reintroduced into an untreated environment. The novel set of
      selective forces after removal of insecticide pressure led to the decline of the
      frequencies of resistant phenotypes over time, suggesting that the insecticide
      adapted genetic variants were selected against the absence of insecticide (with a
      selective coefficient estimated at 0.11). The selective coefficients were also
      estimated for both the major cytochrome P450-dependent monooxygenase (MFO) and
      the minor glutathione S-transferase (GST) systems (0.17 and negligible,
      respectively), which have been previously shown to be involved in resistance. The
      involvement of metabolic systems acting both through xenobiotic detoxification
      and biosynthetic pathways of endogenous compounds may be central to explaining
      the deleterious physiological consequences resulting from pleiotropy of adaptive
      changes. The estimation of the magnitude of the fitness cost associated with
      insecticide resistance in C. pomonella suggests that resistance management
      strategies exclusively based on insecticide alternations would be unlikely to
      delay such a selection process.

PMID- 12522434
TI  - Virotherapy for cancer: current status, hurdles, and future directions.

PMID- 12522435
TI  - RNA viruses as virotherapy agents.
AB  - RNA viruses are rapidly emerging as extraordinarily promising agents for
      oncolytic virotherapy. Integral to the lifecycles of all RNA viruses is the
      formation of double-stranded RNA, which activates a spectrum of cellular defense
      mechanisms including the activation of PKR and the release of interferon. Tumors
      are frequently defective in their PKR signaling and interferon response pathways,
      and therefore provide a relatively permissive substrate for the propagation of
      RNA viruses. For most of the oncolytic RNA viruses currently under study, tumor
      specificity is either a natural characteristic of the virus, or a serendipitous
      consequence of adapting the virus to propagate in human tumor cell lines. Further
      refinement and optimization of these oncolytic agents can be achieved through
      virus engineering. This article provides a summary of the current status of
      oncolytic virotherapy efforts for seven different RNA viruses, namely, mumps,
      Newcastle disease virus, measles virus, vesicular stomatitis virus, influenza,
      reovirus, and poliovirus.

PMID- 12522436
TI  - Oncolytic herpes simplex virus vectors for cancer virotherapy.
AB  - Oncolytic herpes simplex virus type 1 (HSV-1) vectors are emerging as an
      effective and powerful therapeutic approach for cancer. Replication-competent HSV
      1 vectors with mutations in genes that affect viral replication,
      neuropathogenicity, and immune evasiveness have been developed and tested for
      their safety and efficacy in a variety of mouse models. Evidence to-date
      following administration into the brain attests to their safety, an important
      observation in light of the neuropathogenicity of the virus. Phase I clinical
      traits of three vectors, G207, 1716, and NV1020, are either ongoing or completed,
      with no adverse events attributed to the virus. These and other HSV-1 vectors are
      effective against a myriad of solid tumors in mice, including glioma, melanoma,
      breast, prostate, colon, ovarian, and pancreatic cancer. Enhancement of activity
      was observed when HSV-1 vectors were used in combination with traditional
      therapies such as radiotherapy and chemotherapy, providing an attractive strategy
      to pursue in the clinic. Oncolytic HSV-1 vectors expressing "suicide" genes
      (thymidine kinase, cytosine deaminase, rat cytochrome P450) or immunostimulatory
      genes (IL-12, GM-CSF, etc.) have been constructed to maximize tumor destruction
      through multimodal therapeutic mechanisms. Further advances in virus delivery and
      tumor specificity should improve the likelihood for successful translation to the
      clinic.

PMID- 12522437
TI  - Intravascular adenoviral agents in cancer patients: lessons from clinical trials.
AB  - A large number of adenoviral agents are being developed for the treatment of
      cancer. However, the treatment-related death of a patient with ornithine
      transcarbamylase deficiency following adenovirus administration by hepatic artery
      has led to serious concerns regarding the safety of intravascular adenovirus.
      Both replication-incompetent (rAd.p53, e.g., SCH58500) and replication-selective
      (dl1520, aka Onyx-015; CG7870) oncolytic adenoviruses, by intravascular
      administration, are in clinical trials. We review Phases I and I/II results from
      these clinical trials. dl1520 and rAd.p53 were well-tolerated following hepatic
      artery infusion at doses of up to 2x10(12) and 2.5x10(13) particles,
      respectively. At a dose of 7.5x10(13) particles, rAd.p53 was associated with dose
      limiting cardiac output suppression; dl1520 dose escalation did not proceed
      higher than 2x10(12). Intravenous (i.v.) infusions of dl1520 and CG7870 have been
      well tolerated by i.v. infusion at doses of 2x10(13) and 6x10(12), respectively,
      without identification of a maximally tolerated dose to date. Mild/moderate
      transaminitis was demonstrated in some patients on both the hepatic arterial and
      i.v. trials at doses >or=10(12) particles. Interleukin (IL)-6 and IL-10 were
      induced in a dose-dependent manner in most patients, but significant interpatient
      and intrapatient (on repeat doses) variabilities were demonstrated. Evidence of
      p53 gene expression (Ad.p53) or viral replication (dl1520) was demonstrated in
      the majority of patients receiving >or=10(12) particles. Over 100 cancer patients
      have been treated with intravascular adenovirus constructs to date with an
      acceptable toxicity profile; further clinical trial testing appears appropriate
      in cancer patients.

PMID- 12522438
TI  - Selectively replicating viral vectors.

PMID- 12522439
TI  - Development of a replication-selective, oncolytic poxvirus for the treatment of
      human cancers.
AB  - Tumor directed gene therapy for the purpose of destroying cancer cells through
      replicative "oncolysis" or by intratumoral expression of toxic or
      immunostimulatory genes requires an efficient, tumor targeted vector. Vectors are
      limited by inefficient replication in vivo, inefficient tumor targeting, and
      safety concerns. As a unique approach to addressing these limitations, our
      laboratory has studied poxviruses as tumor selective replicating vectors. The
      best in vivo antitumor results achieved to date have been with a mutated WR
      strain of vaccinia virus. The unique advantage of this strain of vaccinia over
      other vectors currently being explored for this purpose is the efficiency of in
      vivo replication. Intradermal injection of 10(6) pfu of the wild type (non
      mutated) vaccinia in non-human primates leads to a 108 cm(2) zone of necrosis in
      8 days - directly related to cellular destruction from viral replication. We have
      mutated the virus through insertional deletion of both the thymidine kinase (TK)
      gene and vaccinia growth factor (VGF) gene. The mutant virus no longer causes
      destruction of normal tissue, but has completely preserved replication efficiency
      in tumor tissue and can safely be delivered systematically to successfully treat
      subcutaneous tumors in mice. Plans are now underway for clinical trials.

PMID- 12522440
TI  - Virotherapy clinical trials for regional disease: in situ immune modulation using
      recombinant poxvirus vectors.
AB  - The ability of viruses to readily infect tumor cells both in vitro and in vivo
      has resulted in their study as antitumor agents through a variety of strategies.
      Replicating and conditionally replicating viruses and recombinant viruses
      encoding genes for toxins and/or prodrugs have been studied for their direct
      antitumor activity with promising results. However, to date, the lack of a
      targettable construct able to localize to all tumors following systemic
      administration has proven to be a major limitation in their use for metastatic
      disease. The ability of a variety of well-characterized viruses to serve as
      vectors for expression of tumor antigens and/or cytokines has also resulted in
      their study as immunotherapeutic agents. In this review, we discuss preclinical
      and clinical data that support the use of recombinant poxviruses as vectors for
      in situ tumor transfection with immune-enhancing cytokines and immune
      costimulatory antigens. We hypothesize that such an approach will ultimately lead
      to enhanced immune recognition of tumor and the development of an effective
      systemic antitumor immune response capable of eradicating primary and metastatic
      tumor foci.

PMID- 12522441
TI  - Armed therapeutic viruses: strategies and challenges to arming oncolytic viruses
      with therapeutic genes.
AB  - Oncolytic viruses are attractive therapeutics for cancer because they selectively
      amplify, through replication and spread, the input dose of virus in the target
      tumor. To date, clinical trials have demonstrated marked safety but have not
      realized their theoretical efficacy potential. In this review, we consider the
      potential of armed therapeutic viruses, whose lytic potential is enhanced by
      genetically engineered therapeutic transgene expression from the virus, as
      potential vehicles to increase the potency of these agents. Several classes of
      therapeutic genes are outlined, and potential synergies and hurdles to their
      delivery from replicating viruses are discussed.

PMID- 12522442
TI  - Adenoviral vectors: systemic delivery and tumor targeting.
AB  - The development of a targeted adenoviral vector, which can be delivered
      systemically, is one of the major challenges facing cancer gene therapy. The
      virus is readily cleared from the bloodstream, can be neutralised by pre-existing
      antibodies, and has a permissive cellular tropism. Clinical studies using the
      ONYX virus have shown limited efficacy, but there are several hurdles to overcome
      to achieve an effective tumor-specific systemic therapy. In this review, we have
      summarized the various strategies used to overcome the limitations of adenoviral
      mediated gene delivery.

PMID- 12522443
TI  - Principles of tumor immunosurveillance and implications for immunotherapy.
AB  - Although antigen loss variants, major histocompatibility (MHC) class I down
      regulation, or the expression of inhibitory molecules may explain the failure of
      immunosurveillance against some tumors, this seems not to apply for many other
      solid peripheral or lymphohematopoietic tumors. Why then is immunosurveillance so
      ineffective and can it be improved? This review focuses on one important aspect
      of tumor immunity, namely the relevance of antigen dose and localization. Immune
      responses in vivo are induced in organized lymphoid tissues, i.e., in lymph nodes
      and spleen. The antigen dose that reaches secondary lymphoid organs over time is
      a crucial parameter that drives antiviral and antitumoral immune responses.
      Tumors use various strategies to prevent efficient presentation of their antigens
      in lymphoid organs. A major obstacle to the induction of an endogenous tumor
      specific cytotoxic T lymphocyte (CTL) response is the inefficient presentation of
      tumor antigen on MHC class I molecules of professional antigen-presenting cells.
      Peripheral solid tumors that develop outside lymphoid organs are, therefore,
      often ignored by the immune system. In other situations, tumors - especially of
      lymphohematopoietic origin - may tolerize specific CTLs. Understanding tumor
      immunosurveillance is key to the design of efficient antitumor vaccines. Attempts
      to improve immunity to tumors include vaccination strategies to (a) provide the
      tumor antigen to secondary lymphoid organs using recombinant viruses or dendritic
      cells as carriers, (b) express costimulatory signals on tumor cells, or (c)
      improve the efficiency of cross-priming.

PMID- 12522444
TI  - Biosafety and product release testing issues relevant to replication-competent
      oncolytic viruses.
AB  - Replication competent oncolytic viruses, like other biological products, are at
      risk from contamination by bacteria, fungi, mycoplasma and viruses that must be
      eliminated from the final product. This article reviews the regulatory guidance
      for the manufacture and testing for oncolytic virus products. A testing strategy
      covering the testing of cell lines, virus banks, virus harvests and purified
      product is described.

PMID- 12522445
TI  - The oncolytic virotherapy treatment platform for cancer: unique biological and
      biosafety points to consider.
AB  - The field of replication-selective oncolytic viruses (virotherapy) has exploded
      over the last 10 years. As with many novel therapeutic approaches, initial
      overexuberance has been tempered by clinical trial results with first-generation
      agents. Although a number of significant hurdles to this approach have now been
      identified, novel solutions have been proposed and improvements are being made at
      a furious rate. This article seeks to initiate a discussion of these hurdles,
      approaches to overcome them, and unique safety and regulatory issues to consider.

PMID- 12522448
TI  - Exclusive TCRVbeta chain usage of ex vivo generated minor Histocompatibility
      antigen HA-1 specific cytotoxic T cells: implications for monitoring of
      immunotherapy of leukemia by TCRBV spectratyping.
AB  - Tissue expression of minor Histocompatibility antigens HA-1 and HA-2 is limited
      to the hematopoietic system. Therefore, ex vivo generated HA-1/HA-2 specific
      cytotoxic T lymphocytes (CTLs) can be applied for adoptive immunotherapy of
      relapsed leukemia after HLA-matched HA-1/HA-2 mismatched stem cell
      transplantation. Here we used T cell receptor beta variable chain (TCRBV)
      spectratyping and/or TCRBV sequencing to monitor the specific TCR usage in eleven
      HA-1/HA-2 CTLs that were induced ex vivo with peptide pulsed dendritic cells. The
      HA-2 induced CTLs used different TCRBV. In contrast, the development of HA-1
      specific CTLs coincided with prominent skewing of TCRBV7 spectratypes. Sequencing
      of the TCRBV7 specific PCR products used by these ex vivo generated HA-1 CTLs
      revealed the exclusive usage of TCRBV7-9*03, identical to the TCRBV used by HA-1
      specific CTLs induced in vivo after stem cell transplantation. Thus, monitoring
      of immunotherapy with HA-1 specific CTLs is now also feasible by TCRBV
      spectratyping.

PMID- 12522449
TI  - A prospective phase II clinical trial with the use of zidovudine and interferon
      alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma ATL is an aggressive T cells malignancy, with poor
      prognosis due to chemotherapy resistance. Preliminary results using zidovudine
      (AZT) and interferon-alpha (IFN) showed high response rate in ATL patients. We
      report a prospective phase II trial using AZT/IFN treatment for aggressive ATL.
      Nineteen ATL patients (15 acute and four lymphoma) were included in this study.
      Thirteen patients received AZT/IFN as initial treatment and six patients after
      initial chemotherapy. For the 17 patients with evaluable tumor, 13 responses were
      obtained with nine complete remissions (CR) and four partial remissions (PR).
      Response rate (RR) was 92% for patients who received AZT/IFN as initial treatment
      (58% CR and 33% PR). Toxicity was mild, mainly hematological. One patient died of
      fulminant viral hepatitis. Fifteen patients relapsed with a median event free
      survival (EFS) of seven months for the whole population (range 1-50+ months), 10
      months for patients who received AZT/IFN as initial therapy and two months for
      patients who received initial chemotherapy. Median overall survival (OS) was 11
      months for the whole population (range 1-82+ months) and 28 months for patients
      who entered CR. Three acute ATL showed prolonged CR (42, 52+ and 84+ months
      respectively) on maintenance therapy with AZT/IFN. This study confirms the
      efficacy and safety of AZT/IFN in ATL with high response and CR rates. Despite
      impressive prolonged CR of more than three years, most of the patients relapse
      stressing the need for additional therapy after achieving CR with AZT/IFN.

PMID- 12522450
TI  - Variable prognostic value of FLT3 internal tandem duplications in patients with
      de novo AML and a normal karyotype, t(15;17), t(8;21) or inv(16).
AB  - INTRODUCTION: Internal tandem duplication of the FLT3 gene (FLT3/ITD) has been
      linked to poor outcome in acute myeloid leukemia (AML). However, the prognostic
      value of FLT3/ITD in various cytogenetic risk groups is still a matter of debate.
      The aim of this study was to evaluate the prognostic significance in patients
      with de novo AML and a normal karyotype or a t(15;17), t(8;21) or inv(16) (good
      risk group). PATIENTS AND METHODS: Diagnostic samples of 100 patients were
      investigated by single-step PCR of exons 11 and 12 of the FLT3 gene in a single
      center retrospective analysis. Subgroups included 53 patients with normal
      karyotype, 21 patients with t(15;17), 9 patients with t(8;21) and 17 patients
      with inv(16). RESULTS: FLT3/ITD was found in 26 out of 100 patients: 30% of
      patients with a normal karyotype and 38% of t(15;17) patients tested positive.
      The complete remission (CR) rates for the ITD(+) or ITD(-) groups were 50 vs 76%
      in normal karyotypes, and 100 vs 53% in t(15;17) patients, while the relapse
      rates were 75 vs 25% in normal karyotypes and 50 vs 42% in t(15;17) patients.
      Overall survival (OS) and disease free survival (DFS) at 5 years were
      significantly different in patients with normal cytogenetics: ITD(+) vs ITD(-):
      OS 6 vs 28% (P<0.003); DFS 13 vs 41% (P<0.02) Interestingly, FLT3/ITD had no
      significant effect on the outcome of t(15;17) patients: ITD(+) vs ITD(-): OS 85
      vs 53% (P=0.056), DFS 45 vs 60% (P=0.6) at 50 months. CONCLUSIONS: These data
      suggest a high prognostic value of FLT3/ITD in patients with normal cytogenetics.
      However, we find no evidence that FLT3/ITD is a predictive marker for patients
      with t(15;17).

PMID- 12522451
TI  - Comparative genomic hybridization and multiplex-fluorescence in situ
      hybridization: an appraisal in elderly patients with acute myelogenous leukemia.
AB  - Comparative genomic hybridization (CGH) and multiplex-fluorescence in situ
      hybridization (M-FISH) were used to evaluate the presentation karyotype in 15 and
      18 patients respectively, aged >/=60 years, with acute myeloid leukemia (AML).
      Conventional G-banded analysis was performed in all patients prior to evaluation.
      Comparative genomic hybridization confirmed the G-banded karyotype fully in 12
      patients and partially in two patients. Normal CGH profiles were observed in
      patients with a normal karyotype and in one patient with a balanced chromosomal
      translocation as the sole cytogenetic aberration. Multiplex-fluorescence in situ
      hybridization provided additional information in two patients with a complex
      karyotype, but failed to detect a telomeric translocation in one patient. Eight
      patients with normal G-banded karyotypes appeared normal by M-FISH. These results
      demonstrate that both CGH and M-FISH analysis correlate well with the G-banded
      karyotype in AML. Furthermore, although additive cytogenetic data was not
      provided by either technique in cases with normal karyotype, DNA copy number
      change and cryptic translocations below the resolution of CGH and M-FISH may
      still be the initiating event for leukemogenesis for these patients.

PMID- 12522452
TI  - Efficacy of rituximab in the treatment of refractory chronic lymphocytic leukemia
      patient with bone marrow aplasia.
AB  - Recently, several reports have been published claiming the efficacy of anti-CD20
      monoclonal antibody (rituximab) in the treatment of B-cell chronic lymphocytic
      leukemia (B-CLL) and some related autoimmune complications. We used anti-CD20
      monoclonal antibody in a patient with advanced stage and heavily pre-treated B
      CLL with a concomitant bone marrow aplasia requiring a remarkable transfusional
      support of both red blood cells and platelets. The treatment was conducted
      according to standard dosage and schedule and the patient did not experience any
      severe side effect. A progressive reduction of transfusions and a certain
      recovery of bone marrow cellularity was observed after six months from the end of
      therapy. This case suggests that rituximab can play a role in this subset of B
      CLL patients with very few effective therapeutic options and in which the
      clinical features may be due both to neoplastic proliferation and concomitant
      autoimmune disorder.

PMID- 12522453
TI  - Commitment of juvenile myelo-monocytic (JMML) leukemic cells to spontaneously
      differentiate into dendritic cells.
AB  - Juvenile myelo-monocytic leukemia (JMML) is a severe malignant stem cell disorder
      of childhood. A proportion of cells from JMML mononuclear cells (MNC)
      spontaneously differentiate in vitro into dendritic cells (DC). We have studied
      MNC from 14 JMML patients, and characterized their functional activity as antigen
      presenting cells (APC). Large cells, differentiated after seven days of culture,
      expressed high levels of MHC II molecules and Mannose Receptor, variable levels
      of CD80 and CD86, and low levels of CD1a. Similar to immature DC, cells from JMML
      had high levels of dextran endocytosis, and were able to elicit proliferation of
      allogeneic T lymphocytes in mixed leukocyte reaction (MLR). CD40L-matured DC from
      JMML was associated with relevant increase of CD80, CD86 and CD83, increased APC
      activity, responded in chemotaxis assays to MIP-3beta and secreted increased
      amounts of macrophage derived chemokine (MDC). Immature DC and CD40L-matured DC
      from JMML produced very low amounts of IL-12, whereas the production of IL-10 was
      higher than normal DC. In line with these findings, they showed defective
      capacity to polarize naive T cells to differentiate into Th1 effectors. These
      results indicate that MNC from JMML are committed to spontaneously differentiate
      into DC with morphological and phenotypical characteristics similar to normal DC.
      The cytokine profile produced by these APC is likely to suppress and not to
      elicit a protective immune response.

PMID- 12522454
TI  - Experiences of a low-intensity anticoagulation regimen for extended secondary
      prevention of venous thromboembolism.
AB  - Extended treatment with vitamin K antagonists for more than 6 months is often
      used for secondary prevention of venous thromboembolism (VTE) in patients at high
      or moderate risk for recurrent events. The intensity of anticoagulant therapy is
      usually maintained at an International Normalized Ratio (INR) of 2-3. An INR of
      1.5-2 might also prevent thromboembolic events with less complications of
      bleeding, but results from randomized trials are not yet available. In a non
      prospective, uncontrolled study 40 patients with a history of VTE and an
      estimated high risk for recurrent events due to several previous events and/or
      thrombophilic defects were, after a median of 11.5 months on regular intensity
      anticoagulation (INR 2-3), switched to a low intensity regimen (INR 1.5-2). In
      six of the patients an estimated high risk for complications of bleeding
      contributed to this decision. After a median follow-up of 36 months (140 patient
      years) recurrent events, complications of bleeding and some basic quality of life
      measurements regarding the new treatment were registered. No recurrent events,
      four minor bleedings and no major bleedings were registered. Twenty-six patients
      preferred an INR of 1.5-2 compared to 2-3. The main reasons for that preference
      were a lower risk for bleeding (13 patients) and less frequent monitoring of the
      INR (18 patients). No patient preferred full-dose anticoagulation at INR 2-3. In
      patients at a high risk for recurrence of VTE an initial period of regular
      intensity anticoagulation, followed by a low-intensity regimen, may provide
      effective and safe secondary prophylaxis.

PMID- 12522456
TI  - Successful rituximab treatment of an EBV-related lymphoproliferative disease
      arising after autologous transplantation for angioimmunoblastic T-cell lymphoma.
AB  - Rituximab treatment of B-cell lymphoproliferative disease following
      transplantation is being evaluated. We describe an Epstein-Barr virus-related B
      cell lymphoma that developed in a 55-year-old woman, one year after autologous
      transplantation for relapsing angioimmunoblastic T-cell lymphoma. Complete
      remission was achieved after four cycles of rituximab and reduced-dose CHOP. This
      case is discussed in the context of severe immunodepression. Monoclonal anti-CD20
      antibodies might restore a balance between T-cell immunosurveillance and EBV
      proliferation in B-cells,

PMID- 12522455
TI  - A fourth case of BCR-FGFR1 positive CML-like disease with t(8;22) translocation
      showing an extensive deletion on the derivative chromosome 8p.

PMID- 12522457
TI  - Platinum compounds and therapy related acute promyelocytic leukemia.
AB  - Therapy related acute promyelocytic leukemia (ta-APL) is a rare complication of
      chemotherapy for other malignant tumors. We report two such cases, one of whom
      was exposed only to carboplatin two years before developing ta-APL and the other
      one was treated with cisplatin, etoposide and bleomycin five years prior to
      developing ta-APL.

PMID- 12522461
TI  - Lipid lowering in hypertension and heart protection: observations from the Anglo
      Scandinavian Cardiac Outcomes Trial (ASCOT) and the Heart Protection Study.

PMID- 12522462
TI  - Renal and cardiovascular considerations for the nonpharmacological and
      pharmacological therapies of obesity-hypertension.
AB  - Obesity-associated hypertension is a common disease that involves a complex
      pathogenesis. Failure to control hypertension (HTN) in obese subjects provides a
      great threat to their renal and cardiovascular functions. The treatment of
      obesity-associated HTN is often difficult, and requires nonpharmacological and/or
      pharmacological approaches. Weight reduction is the cornerstone of the therapies
      of obesity-HTN, as it reverses the multiple components of its pathogenesis. When
      weight loss cannot be sustained or fails, pharmacological means should then be
      used. Angiotensin-converting enzyme inhibitors (ACEI) are the drug of choice:
      they can reduce blood pressure, protect the kidney and heart, and improve the
      metabolic abnormalities in obese subjects. Angiotensin-2 type-1 receptor blockers
      have a renoprotective benefit similar to ACEI, and they provide an important
      alternative to the use of ACEI. Diuretics are very effective in African-American
      obese hypertensives, but small doses should be used to avoid adverse effects on
      metabolic profiles. Long-acting calcium channel blockers are also effective and
      have the advantage of no adverse metabolic effects. Nondihydropyridine calcium
      channel blockers may provide additional renal and cardiovascular protective
      effects. The beta-adrenergic receptor blockers can cause further weight gain and
      metabolic abnormalities in obese subjects; therefore, careful monitoring is
      needed. There are few clinical data that support the efficacy and benefit of
      centrally acting alpha-2 agonists and alpha-adrenergic receptor antagonists in
      the treatment of obesity-HTN.

PMID- 12522463
TI  - Prolactin, testosterone and cortisol as possible markers of changes in
      cardiovascular function associated with urbanization.
AB  - People living in large informal settlements in South Africa showed a significant
      increase in cardio/cerebrovascular disease. This study was undertaken to compare
      the cardiovascular and endocrine parameters of urbanized and rural black female
      and males. The hormone levels such as prolactin, cortisol and testosterone may
      also change with urbanization and could make a contribution to the high rate of
      hypertension. For this study, 1202 black subjects were selected from 37 randomly
      selected rural and urbanized settlements. Resting blood pressure was recorded
      with a Finapres apparatus. Cardiac output, stroke volume, heart rate, total
      peripheral vascular resistance and compliance had been obtained with the Fast
      Modelflow software program. An acute laboratory stressor (hand dynamometer
      exercise) was applied to challenge the cardiovascular system and the measurements
      were repeated. Blood sampling was done and hormone levels were determined by
      biochemical analyses. For females, significant lower levels of cortisol were
      found in the urban strata in comparison with the rural strata. The testosterone
      levels were significantly lower and the prolactin levels significantly higher for
      females in the informal settlements compared with the rural strata. It is
      noticeable that most cardiovascular parameters showed the highest changes with
      the application of the stressor in the informal settlement strata and the lowest
      in people living on farms for both male and female. The prolactin levels in males
      are significantly higher in the informal settlement stratum. Subjects living in
      informal settlements showed a noticeable endocrine pattern of ongoing stress that
      can be associated with changes in the cardiovascular parameters with
      urbanization. This can partly explain the reported high rate of
      cardio/cerbrovascular disease in black South Africans living in informal
      settlements.

PMID- 12522464
TI  - Low fractional diastolic pressure in the ascending aorta increased the risk of
      coronary heart disease.
AB  - Although the fractional pulse pressure in the ascending aorta is related to the
      occurrence of coronary heart disease (CHD) and restenosis after percutaneous
      transluminal coronary angioplasty, the relative values of diastolic pressure in
      the ascending aorta at the onset of CHD have not been reported. The purpose of
      this study was to evaluate whether the relative values of diastolic pressure are
      associated with the risk of CHD. For this study, we enrolled 406 patients with
      chest pain, normal contractions, no local asynergy, and no history of myocardial
      infarction. We measured the ascending aortic pressure using a fluid-filled
      system. To quantify the relative diastolic pressure, we normalised the diastolic
      pressures to the mean pressure and referred to this value as the fractional
      diastolic pressure (FDP). We investigated the association between the FDP and the
      risk of CHD. Low FDP in the ascending aorta was associated with an increased risk
      of CHD. The multiple-adjusted odds ratio of CHD was 1.68 (95% CI, 0.67-4.22) in
      FDP for the middle tertile of the level. The multiple-adjusted odds ratio of CHD
      was 2.20 (1.16-4.75) in FDP for the lowest tertile compared with the highest
      tertile. FDP was associated with the risk of CHD.

PMID- 12522465
TI  - Salt supresses baseline muscle sympathetic nerve activity in salt-sensitive and
      salt-resistant hypertensives.
AB  - The objective of our study was to evaluate the role of the baroreflex control of
      peripheral sympathetic nervous system on the increase of muscle sympathetic nerve
      activity (MSNA) in salt-sensitive (SS) and salt-resistant (SR) hypertensives
      under low salt diet. In phase I mild-to-moderate hypertensive patients (n=5)
      received three diet periods: a first regular salt (RS1), a low salt (LS=20 meq
      Na+/day), followed by a second regular salt diet (RS2) with a 7-day duration of
      each. At the end of each period, sympathetic and heart rate baroreflex control
      were recorded. Baseline MSNA varied (P<0.005) from 18+/-8 (RS1) to 32+/-9 (LS)
      and to 14+/-9 (RS2) bursts per minute (bpm). In phase II additional patients
      (n=6) were included to have baseline MSNA, sympathetic and heart rate baroreflex
      control evaluated at the end of the LS and RS2. For all patients (n=11), there
      was a significant decrease of MSNA from 36+/-4 to 20+/-8 bpm on day 7 of LS to
      RS2 (P<0.05). The response of MSNA to a salt restriction was similar for SS and
      SR patients, who showed a change from 32+/-6 to 18+/-11 and from 36+/-9 to 17+/-7
      bpm for SS and SR on day 7 of LS and RS2 diets, respectively (P<0.05). MSNA
      baroreflex gain was similar during phenylephrine infusions at day 7 of LS and RS2
      (5.1+/-1.6 and 6.1+/-2.9 bpm/mmHg), but it was reduced under LS during sodium
      nitroprusside infusion (19.5+/-4.9 vs 8.9+/-0.7 bpm/mmHg) (P<0.05) for the whole
      group. Baroreflex control of MSNA was also similar during phenylephrine infusions
      under LS and RS2 diets for SS (4.0+/-0.9 and 3.3+/-0.2 bpm/mmHg) and for SR
      patients (10.1+/-2.5 and 5.6+/-1.5 bpm/mmHg). During nitroprusside infusion,
      baroreflex gain was significantly greater under RS2 for SR patients (19.5+/-2.6
      bpm/mmHg) when compared to LS (11.2+/-5.2 bpm/mmHg) and the same significant
      difference was observed among SS patients (14.4+/-4.7 and 9.1+/-3.6 bpm/mmHg
      under RS2 and LS diets, respectively). There was no difference in heart rate
      baroreflex gain between LS and RS2 diets. Data support the hypotheses that (1)
      sodium supresses baseline MSNA in SS and SR hypertensives and (2) sodium
      restriction may impair baroreflex control of MSNA in SR and SS mild-to-moderate
      hypertensive patients during blood pressure reductions.

PMID- 12522466
TI  - Digitalis-like factor response to hyperinsulinemia in human pregnancy, a model of
      insulin resistance.
AB  - Insulin resistance is strongly associated with hypertension and is postulated to
      participate in the elevation of blood pressure, although the mechanisms involved
      are not understood. Recently, we reported that acute increases in plasma insulin
      levels in normal subjects resulted in increased serum levels of a sodium pump
      inhibitor, termed the digitalis-like factor (DLF), which has been implicated in
      both experimental and essential human hypertension. This study looked at the DLF
      response to hyperinsulinemia, achieved by an oral glucose tolerance test (OGTT),
      in the setting of a naturally occurring and self-resolving state of human insulin
      resistance, during third-trimester pregnancy. This model allowed us the further
      opportunity to compare the DLF response to insulin in the same subjects
      postpartum, after resolution of their insulin resistance. Administration of an
      OGTT during pregnancy and postpartum in the same subjects elicited a comparable
      serum glucose response but a significantly greater insulin response during third
      trimester pregnancy, consistent with diminished insulin sensitivity (integrated
      insulin response during pregnancy: 1611+/-236 vs postpartum: 685+/-101 pmol/l,
      P=0.004). The time courses of the glucose and insulin responses were identical
      whether women were pregnant or not. Plasma free fatty acids fell significantly
      and to a comparable degree during pregnancy and postpartum, but the response was
      slower during pregnancy. DLF levels increased in response to oral glucose in both
      pregnant and nonpregnant states. The response was more rapid during pregnancy
      than after. These findings showed that the increment of insulin induced by oral
      glucose during pregnancy caused a more rapid rise in circulating DLF levels than
      it did during the nonpregnant state. At the same time, the response of
      circulating fatty acids to glucose is retarded during pregnancy. This suggests
      that the insulin resistance of pregnancy impairs insulin's influence on
      intermediary metabolism but not its influence on DLF. As a vasoactive substance,
      DLF might contribute to the hypertension characteristic of insulin-resistant
      states.

PMID- 12522467
TI  - Association of polymorphisms of the renin-angiotensin system and bradykinin B2
      receptor with ACE-inhibitor-related cough.
AB  - The use of angiotensin-converting enzyme (ACE) inhibitors to treat hypertension
      has recently increased. However, their use is associated with a persistent dry
      cough in a significant percentage of such patients. The present study was
      designed to assess the contribution of polymorphisms as a genetic marker of ACE
      inhibitor-related cough in a Japanese hypertensive population. Genotyping was
      carried out in 190 patients, 70 with cough and 120 without cough, who had been
      treated with ACE inhibitors. Polymorphisms of ACE insertion/deletion (I/D),
      angiotensin II type 1 receptor (1166A/C), type 2 receptor (3123C/A), and
      bradykinin B2 receptor (-58T/C, exon 1, I/D), were analyzed in these subjects.
      The TT genotype and T allele of bradykinin B2 receptor (-58T/C) were identified
      at a significantly higher frequency in the cough (+) patients than in the cough (
      ) patients. This difference was even more pronounced in women. However, there was
      no significant relationship between polymorphisms of ACE, angiotensin II
      receptors, or bradykinin B2 receptor exon 1, and occurrence of ACE-inhibitor
      related cough. The transcriptional activity of the bradykinin B2 receptor
      promoter is involved in the occurrence of cough, and this new marker may provide
      a valuable tool to detect patients at risk of developing this side effect of ACE
      inhibitors. In conclusion, Susceptibility to develop cough is associated with a
      genetic variant of the bradykinin B2 receptor promoter; thus, it may be possible
      to identify those patients who will develop this adverse reaction to ACE
      inhibitors in advance.

PMID- 12522468
TI  - Comparison of trough effect of telmisartan vs perindopril using self blood
      pressure measurement: EVERESTE study.
AB  - This multicentre study was aimed at comparing the trough effect of telmisartan
      and perindopril on diastolic blood pressure (DBP), using self blood pressure
      measurement (SBPM). A second objective was to compare the data obtained from SBPM
      with those provided by automatic office BP measurement. A total of 441 mild-to
      moderate hypertensive patients were randomised to receive either telmisartan 40
      mg or perindopril 4 mg for a period of 12 weeks. Patients whose clinic DBP
      remained higher than or equal to 90 mmHg at the end of the 6th week (W6) were
      given a double-dose regimen. Office BP and SBPM were performed at baseline (W0),
      at W6 and at week 12 (W12), both with the same automatic device. A greater
      diminution of trough DBP was obtained with telmisartan (-6.6+/-6.7 mmHg) than
      with perindopril (-5.1+/-7.0 mmHg; P=0.018). Regarding clinic BP, the same
      results were observed. Doubling dose was significantly less frequent with
      telmisartan (41%; n=85) than with perindopril (55%; n=115, P=0.005). Mean values
      of SBPM were lower than office BP values, with a difference of a greater
      importance at W0 than at W12: 6.6 vs 4.7 mmHg for systolic blood pressure
      (P<0.005) and 3.2 vs 1.4 mmHg for DBP (P<0.0001). At W12, isolated office
      hypertension was found in 9% of the patients (n=37), while there were 14% of the
      patients (n=55) with isolated home hypertension. In conclusion, the trough effect
      on DBP was statistically higher with telmisartan than with perindopril. SBPM
      values were lower than office BP values, with greater differences before than
      after treatment. About a quarter of the patients were found to be controlled with
      a method but not with the other one.

PMID- 12522469
TI  - Endogenously and exogenously increased noradrenaline exerts sex-different
      responses in human.

PMID- 12522473
TI  - Extensive investigation of patients with mild elevations of serum amylase and/or
      lipase is 'low yield'.
AB  - BACKGROUND: Serum amylase and lipase levels are widely used as markers of
      pancreatic inflammation. However, it would seem that mild elevations of amylase
      and lipase rarely predict significant pancreatic pathology. Pancreatic imaging
      tests are expensive. The gold standard, endoscopic retrograde
      cholangiopancreatography, carries risk of morbidity and mortality. OBJECTIVE: To
      determine whether extensive investigation of patients with mild, nonspecific
      abdominal symptoms and mild elevations of amylase and/or lipase results in a
      significant diagnostic yield. METHODS: Outpatient evaluations were
      retrospectively analyzed over 12 months. Inclusion criteria were nonspecific
      abdominal pain, and mild elevations (less than three times the upper limit of
      normal) of serum amylase or lipase, or both. Exclusion criteria included a
      history of chronic pancreatitis, elevation of liver tests and acute pain
      syndromes. RESULTS: Nineteen patients over the study period met the criteria. Of
      the nineteen patients, 58% had elevation of lipase alone, 21% amylase alone and
      21% had elevations of both. In addition, 89.5% of the patients had nonspecific
      abdominal pain. After imaging with one or more of ultrasound, computed
      tomography, magnetic resonance cholangiopancreatography, endoscopic ultrasound
      and endoscopic retrograde cholangiopancreatography, small bowel follow through or
      hepatobiliary scanning, 78.9% patients were thought to have a normal pancreas. Of
      the remaining patients, 15.8% had mild or equivocal changes of chronic
      pancreatitis, and one patient was found to have a pancreatic tail pseudocyst. The
      average cost of investigation was US$2,255, taking only direct procedural costs
      into account. No patient was found to have malignancy. CONCLUSIONS: The majority
      of patients with nonspecific abdominal pain and isolated elevations of amylase
      and/or lipase (less than three times the upper limit of normal) had no
      identifiable pancreatic pathology. The diagnostic yield in patients with mild
      elevations of lipase alone was particularly poor. The cost effectiveness and risk
      benefit ratio of extensive investigation of this group of patients warrants
      further study.

PMID- 12522474
TI  - Iron deficiency anemia caused by nonspecific (idiopathic) small bowel ulceration:
      an uncommon presentation of an uncommon disease.
AB  - Ulcers of the small bowel are rare, and in most cases are due to infections,
      inflammatory bowel diseases, malignancies or drugs. When none of these causes is
      recognized, they are classified as 'nonspecific' or idiopathic. Such lesions are
      uncommon, and in most cases present with occlusion. A case of a middle-aged woman
      with iron deficiency anemia due to occult bleeding, with negative gastroscopy and
      colonoscopy is presented. The diagnosis of a small bowel pathology resembling
      Crohn's disease was made by small bowel follow through and small intestine
      contrast ultrasonography. An ileal ulcer was identified at surgery, and after
      resection the patient experienced a stable recovery from the anemia without ulcer
      recurrence. Neither histology nor clinical or biochemical features suggested the
      diagnosis of an inflammatory bowel disease. Other possible causes were unlikely
      and the lesion was therefore diagnosed as idiopathic. This report also focuses on
      the need and the modality to investigate the small bowel in iron deficiency
      anemia patients.

PMID- 12522477
TI  - Funding the new biologics--what can we learn from infliximab? The CCOHTA report:
      a gastroenterologist's viewpoint.
AB  - The treatment of severe Crohn's disease is difficult, and approximately 20% of
      patients do not respond to conventional therapy, including corticosteroids and
      immunosuppressives. Infliximab is one of the only treatments of proven efficacy
      in this group. Awareness of its benefits and risks is incomplete, because the
      drug has only recently been introduced and published research data are relatively
      sparse. Economic analyses help to evaluate the value of interventions that are
      both effective and expensive, but their validity is compromised by input data
      that involve questionable assumptions. They should not, therefore, be the only
      basis for funding decisions. Patients with severe Crohn's disease are frequently
      unable to be gainfully employed and thus incur significant indirect costs. In a
      recent study by the Canadian Coordinating Office for Health Technology Assessment
      (CCOHTA), infliximab was deemed to not meet commonly accepted standards of cost
      effectiveness. This economic analysis did not incorporate indirect costs, and
      thus was inherently flawed and likely underestimated infliximab's value. The
      CCOHTA report also used population data from a period of time during which
      treatment of Crohn's disease was undergoing major transition. The study
      population was based in Minnesota and thus might not be applicable to Canada.
      Although they are routinely used in cost effectiveness models, quality-adjusted
      life-years gained are difficult to translate into practice, and the health care
      resources required to induce remission (or some other clinically meaningful
      result) might be a preferable measure. The CCOHTA report also did not include
      concomitant therapy with immunosuppressives, despite growing evidence for its
      benefit. Instead, it considered 'usual care', but, given the lack of effective
      treatment for many patients with Crohn's disease, such an option constitutes 'no
      care' and continued suffering. Economic analyses should not be the only basis on
      which decisions regarding the funding of infliximab, or other new agents, are
      made.

PMID- 12522475
TI  - Causation: Recurrent collagenous colitis following repeated use of NSAIDs.
AB  - A case in which a patient who on two occasions developed watery diarrhea and
      proven collagenous colitis shortly after taking nonsteroidal anti-inflammatory
      drugs is described. The case report suggests a causal relationship.

PMID- 12522478
TI  - Funding the new biologics--public policy issues in drug formulary decision
      making.
AB  - One function of drug formularies is to allow health care providers to exert some
      control over spending. Decisions about whether to include a given medication in a
      formulary are based on estimates of its costs and effectiveness, relative to
      other treatment strategies. These decisions are made from a societal perspective,
      as opposed to that of individual patients, which sometimes results in conflicts.
      The clinical response to a medication often varies widely among subjects, which
      means that a small subgroup of patients might benefit dramatically, while others
      with the same disease do not. The result would be that a drug might appear not to
      be cost effective in an economic analysis, even though it is of proven value for
      some patients. New and innovative medications are assessed according to high
      standards of cost effectiveness, even though established treatments are wasteful
      of valuable health care resources. Moreover, quality-adjusted life-years (QALYs)
      discriminate against certain patient groups, including those with diseases that
      are associated with a high morbidity but a low mortality. Such patients often
      incur high indirect costs, including loss of employment income and costs incurred
      by family caregivers that QALYs do not reflect. Therefore, even though QALYs are
      transparent and widely applicable, they are not necessarily appropriate in the
      evaluation of a particular therapeutic intervention. A new paradigm should be
      developed for evaluating emerging therapies. An example would be a risk-sharing
      approach, whereby the pharmaceutical industry and public insurers share in the
      costs and rewards of introducing new treatments. This would have implications for
      the prices charged for new medications.

PMID- 12522479
TI  - Funding the new biologics--a health economic critique of the CCOHTA report:
      infliximab for the treatment of Crohn's disease.
AB  - The report of the Canadian Coordinating Office for Health Technology Assessment
      (CCOHTA) on the use of infliximab in the treatment of refractory Crohn's disease
      stated that the medication did not meet 'conventional standards of cost
      effectiveness'. It had several methodological weaknesses, however, including the
      derivation of the quality-adjusted life-years (QALYs) gained and the
      interpretation of the incremental cost utility ratios (ICURs). The validity of
      economic analyses is highly dependent on the underlying assumptions that are made
      about the implications of health care states and treatments. The authors of the
      report mapped utilities from three health states, taken from an American study,
      onto the nine health states that were considered in their economic analysis. The
      QALYs that were derived might not have been sensitive to small changes in health
      outcomes. Moreover, the indirect costs of Crohn's disease and its complications
      were ignored. Therefore, it is possible that the benefits of infliximab therapy
      were underestimated. The high ICURs that were quoted in the report do not
      necessarily mean that infliximab is not valuable, because opportunity costs were
      not considered. Instead of calculating the ICUR, a preferable approach would be
      to determine the benefit of this therapy, compared with that which could be
      derived from alternative uses of the same amount of health care resources. A
      'balance sheet' approach would allow decision-makers to determine whether the
      additional cost of infliximab therapy would be justified by the health care gains
      that it produces. It is inappropriate to assign an arbitrary cut-off point to
      cost effectiveness, as defined by ICURs, especially when considering new and
      expensive treatments for severely ill patients who have few other therapeutic
      alternatives. Because only a small number of patients would require infliximab,
      the overall expenditure that would be required to make it available may be
      manageable.

PMID- 12522481
TI  - Preaching to the converted.

PMID- 12522483
TI  - Sustainable tuberculosis control.

PMID- 12522484
TI  - Practice patterns of respirologists in Canada.
AB  - The demographics and practice patterns of respirologists in Canada have not been
      studied. To evaluate the demographic characteristics of respirologists in
      practice, appraise current respirology manpower and ascertain the utilization of
      invasive diagnostic and therapeutic procedures (interventional pulmonology), a
      mail survey of all Canadian respirologists was conducted. The questionnaires were
      completed by 62% (n=355) of 573 possible participants. Of the respirologists who
      responded, 69.2% were younger than 50 years of age, 70.3% had been in practice
      for fewer than 20 years, 64.4% were in full- or part-time academic practice, and
      72.9% were based in urban centres with a catchment population of more than
      250,000. The current ratio of respirologists to population in Canada, assuming a
      total population of 31,000,000, is 1:54,101. In the present survey, only 68.3%
      respirologists practised clinical respirology for 50% or more of their time, and
      half (49.5%) of respirologists devoted more than 50% of their time on
      nonrespirology or nonclinical activities. Thus, the more precise respirologist to
      population ratio appears to be 1:81,000. The current ratio meets the Royal
      College of Physicians and Surgeons of Canada recommendations, and the current
      training programs meet present manpower requirements. With respect to the
      procedures performed, most specialists carried out bedside procedures and
      flexible bronchoscopy; a much smaller number did invasive procedures such as
      rigid bronchoscopy (20.8%), transbronchial needle biopsy of lung (43%),
      transbronchial biopsy of mediastinal lymph nodes (38%), therapeutic bronchoscopy
      using laser, cryotherapy and stents (8.7%), transthoracic needle biopsy (22.2%)
      and thoracoscopy (11.3%). Because 97% of pulmonary specialists would like to
      perform invasive procedures, fellowship programs, mini-residencies and practical
      courses should provide the necessary training.

PMID- 12522485
TI  - Additive effect of dornase alfa and Nacystelyn on transportability and
      viscoelasticity of cystic fibrosis sputum.
AB  - OBJECTIVE: To investigate the effect of dornase alfa (DA), Nacystelyn (NAL) and
      their combination on mucociliary transportability and mucus viscoelasticity of
      cystic fibrosis (CF) sputum, and to assess whether the combination possesses an
      additive effect. DESIGN: Determination of transportability in frog palate and
      viscoelasticity in vitro. SETTING: Research laboratory at a medical centre.
      PATIENTS: Sputa from 15 patients with CF, chronically infected with Pseudomonas
      aeruginosa, were studied. INTERVENTIONS: Sputum samples were incubated without
      any drug solution as a control, and with normal saline, DA, NAL and a mixture of
      DA and NAL in concentrations approximating those achieved in clinical practice.
      RESULTS: Normal saline (10% volume) by itself had a small effect on CF sputum
      transportability with a mean increase of 9%, and on viscoelasticity with a mean
      of decrease of 0.22 log units, respectively, compared with control (incubation
      without saline). DA (200 nM) further increased the transportability by a mean of
      35% versus saline and decreased viscoelasticity by a mean of 0.30 log units. NAL
      (100 M) increased the transportability by a mean of 32% and decreased
      viscoelasticity by a mean of 0.22 log units from the levels achieved with saline.
      The mixture of DA plus NAL at one-half of the above concentration of each agent
      produced an additional increase in the transportability, by a mean of 18%, and a
      further decrease in viscoelasticity, by a mean of 0.25 log units, compared with
      DA or NAL as a single treatment. CONCLUSIONS: The combination of DA and NAL
      exhibits an additive effect for both the viscoelasticity and transportability of
      CF sputum samples. The two agents appear to act well together in breaking down
      the bonding due to extracellular DNA and mucins. Clinical studies should be
      undertaken to see whether the additive combination at lower concentration
      produces the anticipated benefits of improved airway clearance and fewer side
      effects.

PMID- 12522486
TI  - Diagnosing asthma: the fit between survey and administrative database.
AB  - BACKGROUND: Standard methods for population studies of asthma include surveying
      population samples using questionnaires and examining people in laboratories.
      These procedures are extremely expensive. It would be helpful if, at least for
      some purposes, they could be replaced by cheaper techniques with adequate
      validity. OBJECTIVES: To determine agreement between survey and database in
      regard to the prevalence of asthma. METHODS: Responses to survey questions about
      asthma symptoms in the past 12 months were linked to physician claims in the
      Manitoba Population Health Repository. RESULTS: The overall agreement was
      moderate (k=0.45 to 0.50) and increased if two years of physician claims were
      studied (k=0.55 to 0.59); studying additional years had no further effect on
      agreement. Sex and smoking did not significantly affect the kappa scores.
      CONCLUSIONS: There were several plausible reasons for discrepancies. Symptoms
      recorded on the survey were intrinsically different from those recorded for
      physician visits. Physicians also used other respiratory codes instead of asthma,
      and survey participants did not see a physician every year for asthma. The
      estimates of prevalence derived from the survey and the administrative database
      included two overlapping groups of people. In each, the diagnosis of asthma seems
      justifiable, although the agreement between the two groups was only moderate to
      substantial. Both methods are useful, although they are useful for different
      purposes. Health care utilization estimates may be particularly useful for
      studying trends over time.

PMID- 12522487
TI  - Canadian respirologists' experience with lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare pulmonary disease occurring
      primarily in women. A literature review of LAM in Canada found sporadic mention
      of LAM in case reports or within lung transplant studies. The LAM Foundation, a
      patient support and research funding organization, lists 23 Canadian patients in
      its database. The present study was designed to assess the scope of LAM across
      Canada and to identify potential patients for further evaluation. OBJECTIVES: To
      ascertain Canadian respirologists' experience with patients with LAM (current and
      historical), lung transplantation (single or bilateral) and deaths due to LAM,
      and awareness of the LAM Foundation. METHODS: Four hundred twelve brief surveys
      were sent anonymously to members of the Canadian Lung Association (inserted in
      their newsletters) to ascertain the experience of Canadian respirologists with
      LAM. RESULTS: One hundred twelve surveys were returned (27%). Fifty-one
      respondents had "ever" been involved in the care of at least one patient with
      LAM; eight had cared for three or more patients. At the time of the study, 26
      respondents were following a total of 46 patients with LAM; 22 of the 51
      respirologists (43%) who had ever cared for a patient with LAM reported the death
      of a patient. Thirty-three patients had been put on wait lists for
      transplantation; six died while on the wait list. Nineteen patients underwent
      lung transplantation--six single-lung recipients and 13 bilateral lung
      recipients. Of the 51 respirologists who had ever cared for a patient with LAM,
      only 30 (61%) were aware of the LAM Foundation's services. Of the 112
      respondents, only 47 (43%) were aware of the LAM Foundation. CONCLUSIONS: This
      study identified a moderate level of awareness of a significant existing patient
      support and research service (the LAM Foundation). There were many patients with
      LAM who were unknown to the LAM Foundation and could benefit from its resources.
      Results suggest that there may be more patients with LAM in Canada than are
      reported in the existing literature.

PMID- 12522488
TI  - Evaluation of asthma control by physicians and patients: comparison with current
      guidelines.
AB  - BACKGROUND: Current asthma consensus guidelines recommend a series of criteria
      for determining whether asthma is controlled. It is not known whether physicians
      are using these criteria to assess treatment needs and how effective such
      assessments are compared with patient assessment of asthma control. OBJECTIVE: To
      compare the parameters used by physicians and patients with asthma to determine
      whether asthma control is acceptable, according to the current Canadian asthma
      consensus guidelines. DATA AND METHODS: A total of 183 Canadian physicians,
      mostly general practitioners, evaluated 856 patients with mildly to moderately
      uncontrolled asthma who were not using anti-inflammatory medications at the time
      of entry in the study. Physician characteristics and patient demographics were
      obtained. The physicians completed two questionnaires, one assessing the level of
      asthma control of the patient on an ordinal scale from 1 (very poor) to 5 (very
      good) and another indicating the parameters that were used to evaluate this level
      of control. Patients answered an asthma control questionnaire identical to the
      one completed by the physician and completed a six-question asthma control
      questionnaire, with each question scored on a 0- to 6-point scale. RESULTS:
      Although according to current asthma guidelines all patients surveyed had
      uncontrolled asthma, 66.2% of patients and 43.3% of physicians rated control of
      asthma symptoms as adequate to very good. The average scores for patient- and
      physician-rated asthma control were 3.0 0.2 and 2.6 0.2, respectively. The
      average patient score on the Juniper asthma questionnaire was 12.2 6.3.
      Physicians used a mean of seven parameters to assess the patient's level of
      asthma control, mostly beta2-agonist need, followed by cough, wheezing, shortness
      of breath, limitation of physical activities and night-time awakenings.
      Pediatricians used cough more frequently as an evaluation parameter, and
      respirologists measured pulmonary function more often than other physcians. Some
      parameters not usually included in guideline criteria for control, such as
      fatigue, need to clear throat, colored sputum, headache and dizziness, were
      sometimes used by physicians. Only 10% and 18% of physicians used measurements of
      forced expiratory volume in 1 s and peak expiratory flow, respectively, in asthma
      control assessments. CONCLUSIONS: The present study shows that the selection of
      asthma control criteria among physicians varies and is not always in keeping with
      current asthma guidelines. Both patients and physicians often consider asthma to
      be controlled, when according to current guidelines, it is not, and patients
      consider their asthma better controlled than do physicians. Objective measures of
      airflow obstruction are rarely used to assess asthma control. The present study
      stresses the need for improved dissemination - to both patients and physicians -
      of current recommendations on how asthma control should be determined.

PMID- 12522489
TI  - [Histiocytosis X and bronchopulmonary adenocarcinoma: a rare coexistence].
AB  - There exists a rarely observed association between pulmonary histiocytosis X and
      bronchopulmonary cancer. However, the frequency of bronchopulmonary cancer in
      these patients is higher than in the general population. A 28-year-old patient
      who currently smokes ten packs of cigarettes a year came to our department of
      pneumology with complains of cough and hemoptysis. An x-ray of the thorax
      revealed bilateral cysts and a shadow in the upper part of the right pulmonary
      field. In addition, a chest tomography showed multiple cysts dispersed throughout
      the two pulmonary fields and an irregular mass with a diameter of four
      centimetres in the upper right lobe. Bronchopulmonary adenocarcinoma was
      diagnosed during a cytologic exam of the bronchial washing. We decided to perform
      a thoracotomy on the patient, since there was no far metastasis. An upper
      lobectomy and wedge resection of the upper segment of the lower right lobe, which
      had been invaded by the tumour, were performed. Histology confirmed the diagnosis
      of adenocarcinoma. A pulmonary biopsy was carried out on the tumour-free site and
      showed the presence of histiocytosis X. There is a hypothesis that a neoplasm
      developed on the pulmonary fibrosis could be an epiphenomenon of bronchopulmonary
      cancer in patients who smoke and have pulmonary histiocytosis X. It is
      interesting to note that histiocytosis X and bronchopulmonary cancer were
      diagnosed at the same time, since the bronchopulmonary cancer may have occurred
      within a few years following the diagnosis of histiocytosis X, even if she was a
      smoker. Hemoptysis, which is found in 5% of patients with histiocytosis X, may
      suggest cancer. This young patient, a smoker, who complained of hemoptysis, is a
      particularly rare case of the association between pulmonary histiocytosis X and
      bronchopulmonary cancer whose pathogenesis is not clear cut. It is thus important
      to note that smoking can have major consequences, even in young people.

PMID- 12522492
TI  - Nurses and matrons.

PMID- 12522493
TI  - Dame Muriel Powell (1914-1978): role model of a hospital matron and leader of
      nursing.
AB  - Muriel Powell was for 22 years matron of St George's Hospital, London, and for a
      brief period Chief Nursing Officer in the Scottish Home and Health Department in
      Edinburgh. She was an influential role model, an influential leader of and
      spokesperson for her profession, and a member of the government committee that
      recommended the removal of the title "matron" from the National Health Service in
      1968. The title is now being reintroduced and one of the purposes of this paper
      is to highlight the lack of any consideration having been given to the historical
      background of the title and the reasons why it was removed.

PMID- 12522494
TI  - The diet at Christ's Hospital School in the 1920s and the work of a pioneer
      school medical officer, Dr G E Friend.
AB  - The diet at Christ's Hospital in the 1920s is described by the author, who was a
      pupil at the school from 1922 to 1930. The description was checked and confirmed
      by 14 of his surviving contemporaries. The deficiencies of the diet at that time
      are compared with the even worse diets recorded earlier. Great improvements in
      the diet were initiated by a remarkable doctor, G E Friend, when he was the
      school medical officer from 1913 to 1947.

PMID- 12522495
TI  - Constant Lambert: his illness at Christ's Hospital School and the role of Dr G E
      Friend.
AB  - The composer Constant Lambert suffered a near fatal attack of septicaemia while
      he was at school at Christ's Hospital in 1916. His survival owed no small part to
      the school medical officer, Gerald Friend, himself renowned for his work on
      nutrition and development.

PMID- 12522496
TI  - Charles Broady Mingaye Syder (1797-1871): medical temperance pioneer.
AB  - Mingaye Syder was a general practitioner, a medical teacher, a notable writer and
      editor of medical textbooks, and an outstanding early advocate of temperance. He
      started a temperance dispensary, possibly the first of its kind, and was the
      founder and editor of two medical temperance periodicals. Financial success
      eluded him, however, and he was twice imprisoned for debt. He later emigrated to
      Victoria, where he was a country doctor for the last 20 years of his life.

PMID- 12522497
TI  - Francesco Redi (1626-1697): Tuscan philosopher, physician and poet.
AB  - From 1660 to 1697 Francesco Redi was physician to two Grand Dukes of Tuscany as
      well as a natural philosopher and poet at the Medici court. Redi produced the
      first experimental evidence that insects do not spontaneously generate from
      decaying matter and that the poison of the viper resides in the yellow fluid in
      fang sheaths. He was also a pioneer parasitologist. His bacchanalian poem in
      praise of Tuscan wines is still read in Italy today.

PMID- 12522498
TI  - Sydney Monckton Copeman, MD DPH FRCP FRS (1862-1947).

PMID- 12522499
TI  - William Osler and Basil Gildersleeve on Plato's Eryximachus.
AB  - Basil Lanneau Gildersleeve was a colleague of Sir William Osler at the Johns
      Hopkins University. Gildersleeve was a classicist who praised Osler in public but
      who also took him to task for his high opinion of Eryximachus, a character in
      Plato's Symposium. The present paper reviews this dispute between two colleagues
      and explores its origins.

PMID- 12522500
TI  - William Price (1800-1893).

PMID- 12522501
TI  - Alfred Frohlich and his correspondence with Sir Ronald Ross.
AB  - An outline is given of the career of Alfred Frohlich, and his correspondence with
      Sir Ronald Ross between 1901 and 1912 is described in detail.

PMID- 12522502
TI  - What was the cause of Nietzsche's dementia?
AB  - Many scholars have argued that Nietzsche's dementia was caused by syphilis. A
      careful review of the evidence suggests that this consensus is probably
      incorrect. The syphilis hypothesis is not compatible with most of the evidence
      available. Other hypotheses--such as slowly growing right-sided retro-orbital
      meningioma--provide a more plausible fit to the evidence.

PMID- 12522503
TI  - Adolf Kussmaul (1822-1902): from youth to maturity under the influence of
      Virchow.
AB  - Adolf Kussmaul (1822-1902) studied medicine at Heidelberg and Vienna, and
      practised in Kandern in the Black Forest until, in 1854, ill health forced him to
      quit country practice. Drawn by Rudolf Virchow to Worzburg, he took his MD there
      in 1855, after which he held academic posts in Heidelberg, Erlangen, Freiburg and
      Strasburg until 1888, when he retired to Heidelberg and in his closing years
      composed Jugenderinnerungen, memoirs of his youth. Periarteritis (polyarteritis)
      nodosa, pulsus paradoxus, the paradoxical rise in jugular venous pressure on
      inspiration in constrictive pericarditis and the "air hunger" of diabetic ketosis
      are all evidence of shrewd clinical observation and interpretation associated
      with his name.

PMID- 12522504
TI  - Polyamines and fatty acids in sucrose precultured banana meristems and
      correlation with survival rate after cryopreservation.
AB  - Polyamines and fatty acids were studied in proliferating meristem cultures of 3
      banana cultivars with high (Cachaco), medium (Williams Bronze free) and low
      (Mbwazirume) survival rates after cryopreservation. A 2-week preculture on medium
      containing 0.4 M sucrose which is essential to obtain survival after
      cryopreservation resulted in increased polyamine levels, especially putrescine.
      This increase in putrescine content was positively correlated with the survival
      rate after simple freezing or after vitrification. The total fatty acid content
      also increased after a 0.4 M sucrose pretreatment. However, only the ratio of
      unsaturated/saturated fatty acids correlated positively with the survival rate
      after cryopreservation. This is the first report showing a correlation of both
      putrescine increase and level of unsaturation of membrane lipids after sucrose
      treatment with survival rate after cryopreservation.

PMID- 12522505
TI  - Relationship between the changes in cellular volume of fish spermatozoa and their
      cryoresistance.
AB  - We have investigated the hypothesis that the spermatozoa of marine fish are more
      resistant than freshwater species to the dynamic changes in osmotic pressure that
      occur during the process of cryopreservation. We show that while the spermatozoa
      of marine fish can be successfully activated across a wide range of osmotic
      pressures (0-2000 mOsmol/l), those of the freshwater species only survive
      activation within a more restricted range (0-300 mOsm/l). After freeze-thawing,
      up to 30 percent of motile cells were found in silver carp samples, while up to
      90 percent of motile cells were observed in samples from the haarder (Mugil soiuy
      B). Haarder spermatozoa showed no change of cell volume after dilution in
      activating or cryoprotective media, while the silver carp spermatozoa responded
      by swelling and eventual cell disruption. We propose that the differences in
      cryoresistance of silver carp (Hypophthalmichthys molitrix V.) and haarder
      spermatozoa may be determined by the ability to preserve cellular volume under
      non-isotonic conditions.

PMID- 12522506
TI  - The thermal effect of urethral warming during cryosurgery.
AB  - The heating effect of urethral warming during cryosurgery has been investigated
      theoretically, via heat transfer simulations. Two warmer configurations have been
      considered: (i). the clinically available urethral warmer, which has a
      configuration of a counter flow fluid heat exchanger; (ii). a newly designed
      urethral warmer, based on a temperature controlled electrical heater, termed a
      "cryoheater". A dramatic effect of thermal resistance to heat transfer through
      the heat exchanger wall has been identified, which is absent in the cryoheater.
      It follows that the cryoheater is expected to be more efficient in generating an
      unfrozen region around the urethra. It is shown that the conventional heat
      exchanger may fail to prevent freezing around the urethra in a significant number
      of prostate cases, depending on the layout of cryoprobes around the urethra. On
      the other hand, clinical reports exist which suggest that the heat exchanger
      improves in many cases the outcome of cryosurgery, in terms of long term
      complications. It is speculated in the current report that the cryoheater can
      further improve the outcome of cryosurgery, by providing protection from freezing
      in a wider range of cases. It is suggested that a future study be conducted to
      examine the correlation between the layout of cryoprobes and surgical outcome.

PMID- 12522507
TI  - Sucrose preculture to simplify cryopreservation of banana meristem cultures.
AB  - A simple cryopreservation method is described for proliferating meristem cultures
      of banana (Musa spp.). It relies on a 2-week preculture on media containing 0.4 M
      sucrose followed by rapid cooling in liquid nitrogen. Different preculture media
      were screened for efficient protection of banana meristems against
      cryopreservation. Sucrose can be replaced by both fructose and glucose without
      significantly affecting post-thaw survival rates. A high BA concentration (0.1
      mM) in the preculture medium results in less material available for
      cryopreservation, but does not affect cryoprotection. Culture in liquid media
      significantly improved post-thaw regeneration. The optimized cryopreservation
      protocol was applied on 36 banana accessions belonging to 8 different genomic
      groups. It is shown that post-thaw regeneration frequencies (ranging between 0
      and 66 percent) are highly dependent on the genomic constitution of the banana
      cultivar.

PMID- 12522508
TI  - Vitrification of cultured and non-cultured expanded and hatched porcine
      blastocysts.
AB  - The aim of this experiment was to examine the survival of porcine embryos
      following exposure or vitrification in EFS solution. The work was carried out on
      cultured and non-cultured expanded and hatched blastocysts. The viability of
      treated embryos was assessed by their ability to develop in in vitro culture. The
      results showed a higher viability of cultured expanded blastocyst (35.1 percent)
      vitrified in EFS medium compared to those non-cultured (12.5 percent). The
      proportion of cultured hatched blastocyst vitrified in this medium was 13.2
      percent, while none of the non-cultured hatched blastocyst survived
      vitrification. It is concluded that: 1. The EFS solution was more toxic to
      hatched blastocyst than expanded blastocyst 2. The expanded blastocyst was a more
      suitable developmental stage for vitrification than hatched blastocyst. Moreover,
      we demonstrated that the survival rate of vitrified cultured pig blastocyst was
      higher compared to non-cultured.

PMID- 12522509
TI  - An experimental study of the mechanical behavior of frozen arteries at low
      temperatures.
AB  - An experimental study of the mechanical response of frozen arteries to tensile
      stresses at low temperatures is presented. The Dynamic Mechanical Analyzer was
      used to perform the mechanical experiments. It was found that the frozen artery
      shows a kind of elastic-plasticity when the temperature is between -20 C and -40
      C. And with the decrease of the temperature, the plasticity deformation
      decreases. Thus at the temperature of -120 C no plasticity deformation is
      observed before the artery's fracture and the tissue shows quite perfect elastic
      brittleness, both peripherally and axially. These kinds of mechanical
      characteristics help explain the fracture phenomena occurring during
      cryopreservation of the arteries. The mechanical properties, including elastic
      modulus and fracture strength, are also given. It is known that Cryoprotectant
      (CPA) used in cryopreservation is necessary in maintaining the tissue's
      biological functions. Our investigation of its effect on the artery's mechanical
      properties found that the existence of CPA can soften the tissue at low
      temperatures, thus may decrease the possibility of fractures during the
      cryopreservation.

PMID- 12522510
TI  - A custom-built controlled-rate freezer for small sample cryopreservation studies.
AB  - A custom-built controlled-rate freezing machine is described. It operates by
      automatically raising and lowering the sample carrier in a static column of
      liquid nitrogen vapour. It is controlled by a computer-assisted thermocouple
      feedback system that operates a stepper motor driving the sample carrier. The
      cooling protocol is divided into three phases: cooling from +5 to -5 C,
      initiation of ice nucleation, and cooling from -5 to -80 C. Experiments are
      described to validate the device over a range of different cooling rates. A
      freezing protocol is established to cool samples in plastic straws over a range
      of rates up to 80 C/min, with rapid and consistent absorption of the latent heat.

PMID- 12522511
TI  - Free exchange of ideas.

PMID- 12522512
TI  - Pediatric drug development.

PMID- 12522513
TI  - Acute and long-term results after intra-arterial thrombolysis of occluded lower
      extremity bypass grafts using recombinant tissue plasminogen activator for acute
      limb-threatening ischemia.
AB  - Occlusion of lower extremity vascular bypass grafts results in acute limb
      threatening ischemia. The underlying cause of graft failure generally is distal
      anastomosis stenosis, and relief of culprit stenosis is a required to maintain
      long-term patency. Of the three thrombolytic agents used for prolonged infusion
      to accomplish fibrinolysis, streptokinase was the first to be used and is limited
      owing to the antigenicity that precludes repeated use. Urokinase had been the
      mainstay of thrombolytic therapy until it was withdrawn by the U.S. Food and Drug
      Administration in 1999 because of the potential of transmission of infectious
      agents during its manufacturing process. Recombinant tissue plasminogen activator
      (rt-PA) has not been studied adequately to assess safety and efficacy, and there
      are no standardized dosing guidelines. We report our experience with six patients
      presenting with acute limb-threatening ischemia attributable to thrombosis of
      synthetic lower extremity bypass grafts. After thrombolysis using rt-PA (mean
      bolus dose, 12.2 +/- 3.6 mg; range, 6-15 mg administered over 5 minutes followed
      by infusion at 2 mg/h for 15.6 +/- 6.4 hours; total dose, 51 +/- 16 mg),
      successful thrombolysis was achieved in 84% of the patients. The primary patency
      rate was 75% and the secondary patency rate 100% at 16 weeks. One patient
      underwent amputation owing to unsuccessful thrombolysis. No major bleeding or
      vascular complications occurred. We conclude that intra-arterial thrombolysis
      using rt-PA is a safe and effective therapy for patients with thrombotic
      occlusion of synthetic lower extremity bypass grafts presenting with acute limb
      threatening ischemia and allows a high rate of secondary patency, avoiding
      amputation.

PMID- 12522514
TI  - Effect of thrombolytic therapy on QT dispersion in elderly versus younger
      patients with acute myocardial infarction.
AB  - The objective of this study was to assess the degree of QT dispersion and effect
      of thrombolytic therapy on QT dispersion in elderly (age > or =65 years) versus
      younger (age <65 years) patients with acute myocardial infarction. The QT
      dispersion was measured manually in 10 +/- 2 leads of 12-lead electrocardiograms
      on admission, at completion of thrombolytic therapy, and at day 2 after
      thrombolytic therapy in 36 elderly (73 +/- 5.7 years) and 36 younger (59.9 +/-
      7.7 years) patients with acute myocardial infarction. Before initiation of
      thrombolytic therapy, elderly patients had higher absolute and corrected QT
      dispersion than younger patients (absolute QT dispersion: 76.3 +/- 7.3 versus
      69.6 +/- 7.5 milliseconds, respectively, P < 0.0001; corrected QT dispersion:
      77.9 +/- 7.6 versus 70.8 +/- 7.4 milliseconds, respectively, P < 0.001). The
      difference in QT dispersion between elderly and younger patients persisted at the
      completion of thrombolytic therapy (absolute QT dispersion: 75.1 +/- 7.2 versus
      69.1 +/- 8.4 milliseconds, respectively, P = 0.001; corrected QT dispersion: 77.2
      +/- 7.2 versus 70.7 +/- 8.0 milliseconds, respectively, P = 0.001) and at day 2
      after thrombolytic therapy (absolute QT dispersion: 74.1 +/- 8.2 versus 69 +/-
      9.1 milliseconds, respectively, P = 0.01; corrected QT dispersion: 76.0 +/- 7.9
      versus 70.5 +/- 8.8 milliseconds, respectively, P = 0.006). Compared with the
      prethrombolytic values, there was no significant change in absolute and corrected
      QT dispersion at the completion of thrombolytic therapy or at day 2 after
      thrombolytic therapy in elderly or younger patients. Elderly patients with acute
      myocardial infarction have higher QT dispersion than younger patients with acute
      myocardial infarction, and QT dispersion does not change early after thrombolytic
      therapy in elderly or younger patients.

PMID- 12522515
TI  - American pain society pain questionnaire and other pain measures in the
      assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal
      studies.
AB  - The aim of this study was to evaluate the utility of the American Pain Society
      (APS) questionnaire in the assessment of osteoarthritis (OA) pain and to
      determine the onset of action of celecoxib in the treatment of acute flare pain
      in patients with OA of the knee or hip. Pooled data from three pivotal,
      randomized, double-blind, placebo-controlled, 12-week trials of patients with OA
      who exhibited a flare of disease activity after withdrawal of nonsteroidal anti
      inflammatory drug or analgesic therapy were evaluated. Patients completed the APS
      Pain Measure Questionnaire, which evaluates pain intensity and quality of life,
      at baseline and daily for the first 7 days of therapy. In addition, patients
      underwent a range of standard OA assessments to evaluate the analgesic efficacy
      of celecoxib up to 12 weeks. Three thousand two hundred fifty-eight patients were
      enrolled in the three studies, of whom 2041 completed the APS questionnaire (1010
      received celecoxib, 513 received naproxen, and 518 received placebo). Within the
      first 24 hours, celecoxib at a dose of 200 or 400 mg/d significantly reduced the
      amount of acute pain experienced compared with placebo for four of the five
      measures, and statistical significance for the remaining parameter, "pain in the
      last 24 hours," was achieved on day 2. Celecoxib at a dose of 200 to 400 mg/d
      provided similar efficacy to naproxen at a dose of 1000 mg/d. The pain relief
      observed with celecoxib was maintained for the APS evaluation period. Long-term
      efficacy assessments showed the efficacy of 200 mg/d of celecoxib to be
      continuous and maintained for at least the 12 weeks of the study and that it was
      equivalent to 400 mg/d of celecoxib and 1000 mg/d of naproxen. This study
      demonstrates that the APS questionnaire is a useful measure of pain and
      therapeutic response in OA. Celecoxib furthermore seems to be an effective acute
      and chronic analgesic in OA.

PMID- 12522516
TI  - Validation of oxygen saturation measurements in a canine model of hemoglobin
      based oxygen carrier infusion.
AB  - This study was designed to validate oxygen saturation measurements from the NOVA
      CO-Oximeter (NOVA Biomedical Corporation, Waltham, MA), the i-STAT System (Sensor
      Devices, Waukesha, WI), and the Corning 170 blood gas analyzer (Bayer
      Corporation, East Walpole, MA) under conditions similar to the clinical
      application of a hemoglobin-based oxygen carrier (HBOC, hemoglobin glutamer-200
      [bovine]; Oxyglobin, Biopure Corporation, Cambridge, MA). A canine model was used
      for both in vitro and in vivo experiments. In vivo experiments were conducted in
      a canine laboratory, and in vitro experiments were conducted in a tonometry
      laboratory. Study subjects were six mixed-breed dogs, each weighing approximately
      30 kg. In the first set of experiments, the target blood po(2) levels were
      reached by tonometry. In the second set of experiments, quantitative measurements
      of total oxygen content with the LEXO2CON-K (HOSPEX Fiberoptics, Chestnut Hill,
      MA) were performed, immediately followed by measurements with the NOVA CO
      Oximeter and the i-STAT system. HBOC was added in concentrations of 16.2, 32.5,
      65, and 97.5 g/L. To analyze the clinical significance of the differences in the
      results obtained with the each investigated instrument, blood samples from dogs
      treated with HBOC after acute hemorrhagic shock were used. Oxygen saturation,
      oxygen content, and po(2) were measured. There was a strong correlation between
      the oxygen saturation values measured with the investigated instruments in
      samples after tonometry and known po(2). The total calculated oxygen content
      varied by 5% based on results generated by calculations using the investigated
      instruments. The results did not change with different oxygenation of the sample.
      The differences among methods were not significant when the HBOC concentration
      was 16.2 g/L. Higher concentrations of HBOC increased the difference between
      calculated and measured oxygen content; the i-STAT system demonstrated a greater
      deviation compared with the results of the other two instruments. Systemic oxygen
      uptake using the investigated instruments showed a high correlation with values
      based on LEXO2CON-K measurements (R = 0.97 for CO-Oximeter, R = 0.96 for Corning
      170 blood gas analyzer, and R = 0.79 for i-STAT system). Systemic oxygen uptake
      values based on CO-Oximeter and Corning 170 blood gas analyzer data showed 75%
      accuracy; i-STAT system accuracy was 63% for control samples and 50% for samples
      after HBOC infusion.

PMID- 12522517
TI  - Stereoselective pharmacokinetics of amlodipine in elderly hypertensive patients.
AB  - Amlodipine is a dihydropyridine calcium antagonist and is widely used for the
      treatment of cardiovascular diseases. Amlodipine has two stereoisomers [R(+), S(
      )], and only the S(-) isomer exerts vasodilating action. In this preliminary
      study, amlodipine (5 mg) was given to three elderly hypertensive patients once
      daily for 10 days. Blood samples were obtained, and serum concentrations of R(+)-
      and S(-)-amlodipine were measured by a gas chromatographic method. The R(+)/S(-)
      ratio of plasma amlodipine in these elderly subjects was greater than that
      reported in young subjects. These results suggest that the influence of aging on
      the pharmacokinetic profiles might differ between the R(+)- and S(-)-isomers of
      amlodipine.

PMID- 12522518
TI  - Lysis of salmonella typhi intracellularly infected U937 cells by human natural
      killer cells: effect of protein kinase inhibitors.
AB  - We examined the effect of Salmonella typhi (wild-type Ty2 and mutant strain
      TYT1231)-infected U937 cells on natural killer cell (NKC) cytotoxicity of
      peripheral blood mononuclear cells (PBMCs) and highly purified NKC (HPNKCs;
      CD16(+)/CD56(+) > 95%; the rest corresponding to CD3(+) T cells). We also
      analyzed the possible role of various protein kinases involved in natural
      cytotoxicity on these processes. PBMC cytotoxicity against S typhi-infected U937
      cells was significantly higher (paired Student t test; P < 0.05) than its lytic
      effect against noninfected cells (control) at the various effector-to-target cell
      ratios used (30:1 [24.4 +/- 9.7, 25.1 +/- 11.8, and 17.5 +/- 8.6]; 50:1 [26.6 +/-
      9.7, 26.7 +/- 12.8, and 21.2 +/- 7.5] and 70:1 [32.4 +/- 14.4, 30.1 +/- 12.4, and
      23.1 +/- 7.2], respectively). PBMC NKC activity seemed to be dependent on such
      ratios and was similar against both Salmonella strains studied. Approximately
      half of the individual samples tested (n = 12; 8 male and 4 female subjects of
      comparable age) showed at least a 20% specific lysis increase against their own
      control; essentially no changes or smaller increases in NKC activity were
      observed in all other samples. Similar results were obtained using HPNKCs as
      effector cells (5:1 ratio [38.9 +/- 12.3, 43.3 +/- 11.2, and 27.5 +/- 4.9] and
      10:1 ratio [51.3 +/- 9.1, 46.1 +/- 9.8, and 37.7 +/- 15.5, respectively]). In
      general, specimens significantly lysed after incubation with PBMCs responded in a
      similar manner to a challenge with HPNKCs. PBMC and HPNKC cytotoxicity against S
      typhi wild-type-infected U937 cells was significantly decreased in a dose
      dependent manner by the addition of genistein (50-200 micromol) or GFX (0.5-2.0
      micromol) to the cytotoxicity assay mixture. NKC activity was almost completely
      inhibited at the highest genistein and GFX concentrations. In similar
      experiments, wortmannin (100-500 nmol) failed to inhibit PBMC cytotoxicity and
      significantly decreased HPNKC activity only at the highest concentration tested.
      These results show that in the process of NKC recognition and lysis of S typhi
      infected U937 cells, there is not a requisite for full bacterial intracellular
      survival capacity and that S typhi-infected U937 cells are a significantly better
      target than noninfected U937 cells. NKC signaling pathways activated during the S
      typhi-infected U937 cell recognition and lysis process are mainly protein
      tyrosine kinase and protein kinase-C, and they can be blocked by the same protein
      kinase inhibitors known to inhibit natural cytotoxicity.

PMID- 12522519
TI  - Cytokine release of a keratinocyte model after incubation with two different
      Viscum album L extracts.
AB  - When injected subcutaneously, extracts from the white berry mistletoe (Viscum
      album L) lead to a dose-dependent local inflammatory reaction at the injection
      site. From in vitro investigations with V album extracts, the release of
      proinflammatory cytokines from peripheral blood mononuclear cells and from a
      human skin model (Skin(2) model; Advanced Tissue Sciences, La Jolla, CA) is
      known. This shows dose dependence for mistletoe lectin-I in the range of 0.02
      ng/mL to 10.0 ng/mL. In this study, an investigation was conducted of which
      cytokines are released in the skin by the mistletoe lectin-standardized mistletoe
      extracts Viscum album QuFrF (VaQuFrF) and Iscador Qu Spzial (IQuS) (Institute
      Hiscia, Arlesheim, Switzerland) and whether dose dependency exists. The model
      used for this study is the multilayered skin model EpiDerm (MatTek Corporation,
      Ashland, MA), which consists of multilayered keratinocytes. The viability of the
      cell culture was measured after incubation with 0.01, 0.1, 0.2, 0.3, 0.5, and
      15.0 ng/mL VaQuFrF or 0.01, 0.1, 0.2, 0.3, 0.5, 5.0, and 15.0 ng/mL IQuS. The
      release of interleukin (IL)-1alpha, IL-2, IL-6, IL-8, IL-10, IL-12p(40+70), IL
      12p(70), tumor necrosis factor-alpha (TNFalpha), interferon (IFN)-alpha,
      IFNgamma, granulocyte macrophage-colony stimulating factor, and RANTES was
      determined after incubation with 0.5 ng/mL of IQuS ng/mL and VaQuFrF. The dose
      dependency of the release of IL-1alpha and IL-6 after incubation with 0.5 and
      15.0 ng/mL VaQuFrF or 0.5 ng/mL, 5.0 ng/mL, and 15.0 ng/mL IQuS and that of the
      release of IL-1alpha, IL-2, IL-6, IL-10, and TNFalpha after incubation with 0.01
      ng/mL, 0.1 ng/mL, 0.2 ng/mL, 0.3 ng/mL, and 0.5 ng/mL VaQuFrF or IQuS were
      determined. A dose-dependent decrease of cellular viability and an increase of IL
      1alpha, IL-6, and TNFalpha as well as the release of IL-8 could be demonstrated.
      These results are compatible with the hypothesis that the subcutaneous injection
      of VaQuFrF and IQuS leads to a release of proinflammatory cytokines at the
      injection site.

PMID- 12522520
TI  - Safety of therapeutic beta-blockade in patients with coexisting bronchospastic
      airway disease and coronary artery disease.
AB  - Atherosclerotic coronary artery disease and bronchospastic airway disease
      frequently coexist in older patients. There are substantial data suggesting
      reduced mortality with the use of beta-adrenergic blocking drugs in patients with
      symptomatic coronary artery disease, especially patients who have postmyocardial
      infarction and/or severe coronary artery disease associated with left ventricular
      dysfunction. Conversely, the use of beta-adrenergic blocking drugs (even
      selective beta(1)-adrenergic blocking drugs) has the potential of exacerbating
      bronchospasm. This prospective registry evaluates the safety of use of selective
      beta(1)-adrenergic blocking drugs in patients with symptomatic coronary artery
      disease and bronchospastic airway disease. A total of 835 consecutive patients
      with symptomatic coronary artery disease were prospectively evaluated for
      coexisting coronary and bronchospastic airway disease. Of these, 30 patients
      (mean age: 61 +/- 14 years) met the qualifying inclusion criteria. All these
      study patients except 1 (29/30 [96%]) reached therapeutic beta-blockade (resting
      heart rate <70 beats per minute). The 1 patient who discontinued use of beta
      adrenergic blocking drugs as a result of lifestyle-limiting bronchospasm had no
      serious adverse outcome. No hospitalizations were required because of worsening
      bronchospasm. Ten percent of patients reported increased requirement of inhaled
      beta(2)-agonist use. The patients were followed for 15 +/- 9 months. One patient
      died of stroke at 22 weeks of follow-up. In conclusion, use of selective beta(1)
      adrenergic blocking drugs at a therapeutic dose is safe (as long as careful
      clinical follow-up is available) and should be considered in all patients with
      coexisting symptomatic coronary artery disease and bronchospastic airway disease.

PMID- 12522521
TI  - Possible pathomechanism of autoimmune hepatitis.
AB  - The hepatotropic viruses, measles, and herpesviruses as well as different drugs
      were repeatedly shown to act presumably as a trigger in patients with autoimmune
      hepatitis (AI-H). On the other hand, it is known that viral infections stimulate
      interferon production, which inactivates the cytochrome P-450 enzymes involved in
      the metabolism of several endogenous substances and exogenous environmental
      agents. Moreover, it was reported that several cytokines, including interferons,
      as well as transforming growth factor beta1 and human hepatocyte growth factor,
      which are abundantly produced and released in the body during infections, also
      downregulated expression of major cytochrome P-450 and/or other biotransformation
      enzymes. It seems that all these factors, in addition to individual immune
      response and the nature and amount of the neoantigen(s) produced, impair the
      equilibrium of bioactivation and detoxication pathways, thus leading to the
      development of AI-H in a genetically predisposed person continually exposed to
      harmful environmental factor(s). Possible increased/decreased density of lysine
      residues at position D-related human leukocyte antigen locus (DR)beta71 of the
      antigen-binding groove may affect the eventual steroid-sparing effect of this
      critical amino acid at the cellular level. In addition, some food additives, such
      as monosodium glutamate (MSG) and/or aspartame regularly consumed in excessive
      amounts, may eventually disturb the delicate balance between a positively charged
      amino acid residue at position DRbeta71 (lysine or arginine) and a negatively
      charged amino acid residue at position P4 on the antigenic peptide (glutamic acid
      or aspartic acid). This may favor formation of a salt bridge between these amino
      acid residues within the hypervariable region 3 on the alpha-helix of the DRbeta
      polypeptide and facilitate autoantigen presentation and CD4 T-helper cell
      activation. MSG and aspartate may also depress serum concentrations of growth
      hormone, which downregulate the activity of several cytochrome P-450 hepatic and
      other drug-metabolizing enzymes, thus increasing sensitivity to some
      environmental agents and possibly influencing efficacy of treatment regimens and
      final outcome of patients with type 1 AI-H.

PMID- 12522522
TI  - Torsade de pointes associated with the administration of intravenous haloperidol.
AB  - Torsade de pointes is a malignant dysrhythmia that has been reported in a variety
      of clinical settings and associated with several pharmacologic agents. Patients
      with a prolonged QTc for heart rate are at higher risk for the development of
      this arrhythmia. We review the literature supporting the relationship of
      haloperidol to the development of this malignant dysrhythmia. Clinicians in the
      critical care setting should be aware of potentially lethal drug-induced
      ventricular tachydysrhythmias such as torsade de pointes.

PMID- 12522523
TI  - Comorbidity of irritable bowel syndrome in psychiatric patients: a review.
AB  - Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is
      present in 10% to 20% of the U.S. adult population. The syndrome is best defined
      as chronic abdominal discomfort with changes in stool frequency, consistency, and
      passage, with associated symptoms such as abdominal bloating or presence of mucus
      in stools. Several studies have shown that up to 70% to 90% of patients with IBS
      who seek treatment have psychiatric comorbidity, most notably mood and anxiety
      disorders. Recent studies have shown a high prevalence of IBS in psychiatric
      patients who seek treatment, with a prevalence of 19% in schizophrenia, 29% in
      major depression, and 46% in panic disorder among other disorders. Our article
      reviews the comorbidity of IBS in psychiatric patients and discusses implications
      for treatment.

PMID- 12522524
TI  - Antidote review: fomepizole for methanol poisoning.
AB  - Fomepizole (Antizol) was recently approved by the US Food and Drug Administration
      for treatment of methanol poisoning. By inhibiting the hepatic enzyme alcohol
      dehydrogenase, it presents formation of toxic metabolites with far fewer
      consequences than traditional ethanol therapy. It appears that fomepizole will
      become standard therapy for methanol intoxication as it is for ethylene glycol
      poisoning.

PMID- 12522525
TI  - Alcohol-triggered acute myocardial infarction.
AB  - Heavy alcohol drinking may trigger the onset of acute myocardial infarction.
      Although the underlying mechanisms are poorly understood, alcohol-induced changes
      in blood homeostasis, endothelial dysfunction, decreased fibrinolysis, and
      coronary spasm are the possible explanations. There are rare reports of acute
      myocardial infarction in young individuals triggered by acute heavy alcohol
      intake. We present a case of acute ST segment elevation myocardial infarction
      triggered by heavy alcoholic binge drinking in a man and discuss the available
      explanations of this rare association.

PMID- 12522526
TI  - Acute pulmonary edema after successful electrical cardioversion of atrial
      fibrillation.
AB  - Acute pulmonary edema is a rarely reported complication of electrical
      cardioversion. Most of such cases have been reported after cardioversion of
      atrial fibrillation. Most of the patients who have been reported to develop
      postcardioversion acute pulmonary edema had hypertensive or valvular heart
      disease. We report a case of postcardioversion acute pulmonary edema after
      electrical cardioversion of atrial fibrillation in a patient with severe mitral
      regurgitation.

PMID- 12522527
TI  - Peripartum acute myocardial infarction: management perspective.
AB  - Acute myocardial infarction in pregnancy and puerperium is an uncommon event with
      substantial morbidity and mortality rates. Atherosclerosis may be the cause, but
      often the coronary arteries are healthy at angiography. In such cases, the
      suggested mechanism is a decreased coronary perfusion related to coronary spasm
      or in situ thrombosis. Most pregnant women who died after myocardial infarction
      did so at the time of initial infarction, and maternal mortality was greatest if
      the infarction was late in pregnancy. Increasing cardiovascular stresses of late
      pregnancy, especially when intensified by parturition, seriously compromise women
      with ischemic heart disease. Therefore, there should be efforts to limit
      myocardial oxygen demand throughout pregnancy, and particularly during
      parturition. It is important for diagnosis to have increased awareness of its
      possible occurrence. Although principles of management can be generalized, it is
      necessary to provide individualized care for these high-risk patients by a
      multidisciplinary team of cardiologists, anesthesiologists, and obstetricians.

PMID- 12522528
TI  - Clinical therapeutic conference.

PMID- 12522529
TI  - The role of TGF-beta in digestive organ disease.

PMID- 12522530
TI  - Expression of inducible nitric oxide synthase in the lower esophageal sphincter
      of the endotoxemic opossum.
AB  - BACKGROUND: Endotoxin modulates esophageal motor function by increasing nitric
      oxide (NO) production. The aims of this study were to examine inducible nitric
      oxide synthase (iNOS) induction in the lower esophageal sphincter (LES) of
      endotoxemic opossums and to investigate the effects of aminoguanidine (AG), a
      selective inhibitor of iNOS, on plasma nitrite/nitrate levels and on iNOS protein
      and mRNA expression after exposure to lipopolysaccharide (LPS). METHODS: Before
      and 12 h after the intravenous administration of LPS and/or AG, plasma
      nitrite/nitrate levels were determined. The iNOS protein and mRNA expression were
      investigated in the tissues taken from the LES by Western blot and reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: Plasma nitrite/nitrate
      levels were significantly increased by LPS. The increase in plasma
      nitrite/nitrate produced by LPS was significantly decreased by AG. Western blot
      and RT-PCR demonstrated that iNOS expression was markedly increased by LPS, and
      attenuated slightly by AG. CONCLUSIONS: These studies support the hypothesis that
      endotoxin increases NO production by the induction of iNOS protein and mRNA.

PMID- 12522531
TI  - Helicobacter pylori infection in hospital workers over a 5-year period:
      correlation with demographic and clinical parameters.
AB  - BACKGROUND: We aimed to determine whether any of various groups of medical and
      nonmedical staff in a large acute care hospital were at increased risk of
      acquiring Helicobacter pylori infection over a 5-year period, and we also aimed
      to identify risk factors or symptoms related to H. pylori positivity and
      seroconversion. METHODS: A total number of 437 subjects, aged 36.8 +/- 7.7 years
      (range, 23-60 years)-employees of our hospital-were tested by immunoassay for
      serum IgG antibodies against H. pylori. Subjects were assigned to four main
      groups: (I) nursing staff ( n = 249; aged 34.7 +/- 7 years); (II) administrative
      and technical staff ( n = 127; aged 39.2 +/- 8.1 years); (III) medical staff ( n
      = 31; aged 42.4 +/- 4.9 years); and (IV) paramedical staff (blood donor
      department) ( n = 30; aged 37.6 +/- 8.5 years). Differences in age and
      educational level between these four groups were statistically highly significant
      ( P < 0.0001). Each subject completed a questionnaire containing several clinical
      and demographic parameters. The same cohort of individuals was tested 5 years
      later. RESULTS: The overall seroprevalence of H. pylori infection was 45.5%, and
      in each group (I, II, III, and IV) being 48.6%, 44.1%, 41.9%, and 30%
      respectively. Logistic regression analysis revealed that the risk of infection by
      H. pylori was significantly higher in group I compared with group II (odds ratio
      [OR], 1.91; 95% confidence interval [CI], 1.04-3.52; P = 0.037). The H. pylori
      positivity increased with age: 40.6% for those aged 23-40 years and 57.5% for
      those aged 41-60 years ( P = 0.001). The level of education was inversely
      associated with H. pylori infection ( P = 0.001). During the 5-year observation,
      59 of 238 (24.8%) subjects initially negative for H. pylori infection became
      positive, thus giving an annual seroconversion rate of 4.95%. Logistic regression
      analysis revealed that the seroconversion rate was significantly higher in group
      I compared with group II (28.1% vs 21.1%; OR, 2.34; 95% CI, 1.08-5.07; P = 0.03).
      The rate of seroconversion was higher in subjects aged 35-55 years compared with
      subjects aged 23-34 years (32% vs 17.5%; P= 0.009). Subjects who were positive
      for H. pylori infection in both examinations had a higher percentage of heartburn
      ( P = 0.029), regurgitation ( P = 0.023), and nausea ( P= 0.037) compared with
      those who were negative in both examinations. Differences between those who were
      continuously negative for H. pylori infection and those who seroconverted during
      the observation period were not significant. CONCLUSIONS: In this longitudinal
      study of workers in a large acute care hospital in Greece it was found that
      nursing staff had a significantly higher risk of infection compared with
      administrative and technical staff. Age was significantly positively related both
      to H. pylori infection and to seroconversion. The level of education was strongly
      related to the prevalence, but not to the incidence of H. pylori infection. The
      presence of infection over the time was associated with a higher percentage of
      heartburn, regurgitation, and nausea compared with subjects who were continuously
      negative for H. pylori infection.

PMID- 12522532
TI  - Lactose intolerance: a risk factor for reduced bone mineral density and vertebral
      fractures?
AB  - BACKGROUND: The purpose of the present study was to determine differences, if
      any, in bone mineral density, the risk of fracture, and clinical behavior in
      patients with lactose intolerance investigated by hydrogen breath test. METHODS:
      The study population (n = 218; age, mean +/- SD, 58.2 +/- 11.5 years) consisted
      of 103 healthy individuals negative hydrogen breath test (Delta H2 0-20 ppm;
      group I), and 115 individuals with evidence of lactose intolerance according to
      the hydrogen breath test (Delta H2 > 20 ppm), of whom 40 individuals had test
      results of 20 ppm < Delta H2 < 59 ppm (group II). The remaining 75 individuals
      were strongly positive on the hydrogen breath test (Delta H2 > 60 ppm; group
      III). The entire study population was measured for bone mineral density in the
      nondominant forearm and in the vertebra (quantitative computed tomography [qCT]).
      Radiographs of the spine were studied for fractures. RESULTS: In healthy
      individuals, bone mineral density in the vertebra assessed by qCT (mean +/- SD,
      111.2 +/- 31 mg/cc) did not significantly differ between those with mild (qCT,
      mean +/- SD, 109.8 +/- 35 mg/cc) and those with severe (qCT, mean +/- SD, 107.7
      +/- 36 mg/cc) lactose intolerance. Lactose-intolerant individuals had more
      vertebral fractures per patient when compared with those with mild lactose
      intolerance or controls ( P < 0.05). Considering vertebral and self-reported non
      vertebral fractures, no statistically significant differences were found. In the
      entire group, the overall occurrences of fracture in the presence of lactose
      intolerance and in controls were comparable after correction for age and body
      mass index (BMI). CONCLUSIONS: Individuals with lactose intolerance verified by
      the hydrogen breath test appear not to be at risk for accelerated bone loss.
      Nevertheless, a relationship between vertebral fractures and an apparent lactose
      intolerance cannot be excluded, as a few individuals with severe lactose
      intolerance had a large number of vertebral fractures.

PMID- 12522533
TI  - Free perforation in Crohn's disease: review of the Japanese literature.
AB  - BACKGROUND: Reports of free perforation in Crohn's disease have been increasing
      in Japan. In this study, we investigated the characteristics of free perforation
      in Japanese patients with Crohn's disease. METHODS: We reviewed the data for 104
      patients with free perforation in Crohn's disease reported in the Japanese
      literature, in addition to 22 patients from our hospital. RESULTS: There were 89
      men and 37 women in this series, with ages ranging from 16 to 92 years. Free
      perforation was the presenting sign of the disease in 72 patients. The
      perforation sites were the jejunum in 7, the ileum in 102, and the colon in 17.
      Multiple perforations occurred in 13 patients. Steroid therapy was administered
      in 25 patients, but the relation between steroid therapy and free perforation had
      not been well established. The incidence of free perforation in Crohn's disease
      in Japan was between 2.9% and 10.5%. This incidence was higher than that in
      Western countries. Ninety-eight patients were treated with resection and
      drainage, and 22 patients with resection and diversion (details were not known in
      6 patients). There were no patients with simple closure of the perforation site.
      Anastomotic rupture occurred in 13 patients. Five patients died after the
      operation. Four of these five patients had multiple perforations. CONCLUSIONS:
      The incidence of free perforation in Japan is higher than that in Western
      countries and patients with multiple perforations have a poor prognosis.

PMID- 12522534
TI  - Risk factors for infections in cirrhotic patients with and without hepatocellular
      carcinoma.
AB  - BACKGROUND: Patients with liver cirrhosis (LC) frequently have complications with
      bacterial infections, and these infections increase the mortality rate. However,
      a detailed analysis of infections associated with LC patients has not yet been
      performed. METHODS: We analyzed 325 patients with LC with and without
      hepatocellular carcinoma (HCC) who were hospitalized between 1997 and 1999.
      RESULTS: Infections developed in 70 (21.5%) patients and 48 (68.6%) of these
      developed infections during hospitalization. The mortality rate of 28.6% (20/70)
      in patients with infectious complications was higher than that of 12.5% (32/255)
      in patients without infectious complications. Forty (57.1%) of the 70 patients
      had infections of unknown causes; 11 (15.7%) had sepsis; 6 (8.6%) had intravenous
      hyperalimentation (IVH) infection; 3 (4.3%) each had spontaneous bacterial
      peritonitis (SBP), liver abscess, and cholecystitis; and 4 (5.7%) had other
      infections. Bacterial cultures of blood were prepared from 73 of the 325 patients
      (22.5%), and were positive in 22 of the 73 patients (30.1%). Of these 22 culture
      positive patients, 11 had sepsis, 6 had IVH infection, 2 had liver abscess, 1 had
      cholecystitis, 1 had pneumonia, and 1 had decubitus ulcer. Gram-positive
      bacterial strains were detected most frequently, in 16 of the 24 strains
      isolated. Univariate analysis revealed significant differences between the groups
      with and without infectious complications with regard to hepatitis B virus
      infection, Child-Pugh classification, ascites, esophageal varices, survival rate,
      total-bilirubin (T-Bil), albumin (Alb), lactate dehydrogenase (LDH), total
      cholesterol (T-chol), and prothrombin time (PT). On multivariate analysis, the
      Alb level was selected as a significant independent factor contributing to the
      development of infections. CONCLUSIONS: Patients with advanced cirrhosis with low
      Alb levels should be carefully treated, and the administration of broad spectrum
      antibiotics covering gram-positive bacteria needs to be considered in the
      treatment of infections.

PMID- 12522535
TI  - Different antibody responses against hepatitis B surface antigen among mouse
      strains transfected with mutant viral DNA.
AB  - BACKGROUND: Rapid seroconversion from hepatitis B surface antigen (HBsAg) to anti
      HBs antibody is seen in most patients with fulminant hepatitis B. It is unclear
      whether viral mutation or host immune background is responsible for such enhanced
      host reaction to hepatitis B virus (HBV). To investigate interaction between
      virus mutation and host immune background, we established a mouse model of
      hepatitis B using liposome-mediated gene transfer. METHODS: A mixture of
      liposomes and full-length viral DNA derived from hepatitis B patients was
      injected into three strains of purebred mice intrahepatically. After injection,
      HBsAg and antibody in liver and serum were serially measured. RESULTS: Three days
      after transfection, viral transcript and antigen were detected in the liver and
      serum. Ten days after transfection with wild-type DNA, hepatitis B surface
      antibody was detectable in two of the three strains. Mice that did not produce
      antibody after transfection with wild-type DNA produced a high amount of serum
      antibody against surface antigen when transfected with fulminant hepatitis
      associated DNA. CONCLUSIONS: The present results are consistent with previous
      clinical observations of rapid HBsAg seroconversion in patients with fulminant
      hepatitis B. Further studies are needed to determine which mutations are
      responsible for differences in immunogenicity between HBV strains.

PMID- 12522536
TI  - Shedding of Fas ectodomain that affects apoptosis of hepatocytes occurring in
      regenerative liver.
AB  - BACKGROUND: On the basis of comprehending several membrane proteins undergoing
      ectodomain shedding, including tumor necrosis factor (TNF) alpha receptors, we
      want to know if Fas (CD95/APO-1), which belongs to the TNF receptor (TNFR)
      superfamily and transduces signals resulting in apoptosis upon binding of Fas
      ligand (L) or agonistic anti-Fas antibody, is shed on its ectodomain during liver
      regeneration METHODS: After purification of the total membrane protein of
      hepatocytes, we analyzed Fas ectodomain shedding, using Western blotting, and
      determined the effect of Fas shedding on the apoptosis of hepatocytes by a
      statistical method relevant to apoptosis. RESULTS: Fas protein ectodomain
      shedding occurred at 2, 12, and 36 h after partial hepatectomy, and its level
      decreased at 2 months after partial hepatectomy. The same results were gained
      from in-vitro cultured hepatocytes induced by serum from rats after partial
      hepatectomy. The sensitivity of hepatocytes to agonistic anti-Fas antibody
      increased significantly after they were treated with serum from rats after
      partial hepatectomy. However, the expression of Fas mRNA and Fas protein did not
      affect the liver regeneration. CONCLUSIONS: Fas ectodomain shedding might be an
      important mechanism in controlling hepatocyte apoptosis during liver
      regeneration.

PMID- 12522537
TI  - The influence of conditioned medium from mouse intestinal epithelial cells on the
      proliferative activity of crypt cells: role of granulocyte-macrophage colony
      stimulating factor.
AB  - BACKGROUND: The aim of this work was to study the influence of soluble factors
      produced by native mouse intestinal epithelial cells (IECs) on the proliferative
      activity of freshly isolated intestinal crypt cells. METHODS: The crypt cells
      were cultured with either conditioned medium and its ultrafiltrates or
      recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      the presence or absence of neutralizing anti-GM-CSF antibodies. GM-CSF in culture
      medium was identified by the electrochemiluminescence method. RESULTS: It was
      demonstrated that the IEC conditioned medium contained GM-CSF. This cytokine led
      to both the upregulation and downregulation of crypt cell proliferative activity,
      depending on its concentration in the culture medium. The effect of native GM-CSF
      was reproduced with recombinant mouse GM-CSF: 25 and 5 ng/ml inhibited the
      proliferative activity, whereas 1 ng/ml led to its significant stimulation.
      CONCLUSIONS: Freshly isolated murine IECs produce GM-CSF, which plays a critical
      role in crypt cell proliferative activity in vitro. These results suggest the
      involvement of this factor in the regulation of the crypt proliferative zone, in
      an autocrine and/or paracrine manner.

PMID- 12522538
TI  - Gastropleural fistula derived from malignant lymphoma.
AB  - An 88-year-old man developed pneumothorax and pleural effusion. After the finding
      of ingesta in the pleural effusion, a gastropleural fistula was diagnosed. A
      biopsy specimen of the stomach revealed non-Hodgkin lymphoma, diffuse large-cell,
      B-cell type. Autopsy examination demonstrated that the malignant lymphoma had
      originated from high-grade gastric mucosa-associated lymphoid tissue (MALT)
      lymphoma. Gastropleural fistula is an uncommon condition, as the diaphragm forms
      a thick barrier between the stomach and the thoracic cavity. We review 25
      reported cases of gastropleural fistula found in a MEDLINE search from 1966 to
      2000. In only 3 of the 25 patients was malignant lymphoma reported to have caused
      the gastropleural fistula.

PMID- 12522539
TI  - APC gene mutations in a jejunal adenoma causing intussusception in a patient with
      familial adenomatous polyposis.
AB  - Adenomatous polyps of the jejunum/ileum in patients with familial adenomatous
      polyposis (FAP) are usually small (<5 mm) and are considered to be of little
      clinical importance. Genetic alterations in these polyps have not previously been
      analyzed. We herein report an extremely rare case of FAP presenting with
      intussusception caused by jejunal adenomas. Both somatic and germline mutations
      of the APC gene were detected in one of the polyps. A 40-year-old man with FAP
      was admitted for closure of an ileostomy that had been created because of an
      anastomotic leak after subtotal proctocolectomy with ileo-anal-canal anastomosis.
      During the follow-up after that surgery, he had occasionally complained of
      colicky abdominal pain, but it had quickly subsided. At the second laparotomy,
      for closure of the ileostomy, jejuno-jejunal intussusception was incidentally
      found, and segmental resection of the jejunum, including the leading point of the
      intussusception, was performed. There were five polyps clustered in the resected
      jejunum. Histologically, the polyps, ranging from 5 to 26 mm in diameter, were
      adenomas with moderate to severe atypia. Genetic examinations of one of the
      largest polyps, using polymerase chain reaction single-strand conformation
      polymorphism (PCR-SSCP) and direct sequencing methods, revealed somatic (T
      insertion at codon 1557) and germline mutations (4 base-pair deletion at codons
      181-182) of the APC gene. This is the first evidence that the coexistence of
      somatic and germline alterations in the APC gene is involved in the development
      of a jejunal adenoma causing small-bowel intussusception.

PMID- 12522540
TI  - A pancreatic abscess 7 years after a pancreatojejunostomy for calcifying chronic
      pancreatitis.
AB  - We present herein a case of a 75-year-old Japanese man who had developed a
      pancreatic abscess 7 years after a longitudinal pancreatojejunostomy for chronic
      pancreatitis. The patient, a heavy drinker of alcohol, underwent surgical
      decompression of a ductal obstruction to relieve persistent abdominal pain due to
      severely calcifying chronic pancreatitis. After the surgery, he stopped drinking
      alcohol and was treated with insulin to control secondary diabetes mellitus.
      Thereafter, his symptoms disappeared. Seven years after the surgery, however, he
      was hospitalized due to obstructive jaundice, high-grade fever, and right
      hypochondria pain. Ultrasound and computed tomographic scans of the abdomen both
      disclosed a cystic mass, approximately 6 cm in size, in the pancreatic head.
      Magnetic resonance imaging strongly suggested a pancreatic abscess with necrotic
      fluid and debris. First, percutaneous transhepatic cholangiodrainage (PTCD) was
      done to treat the progressively obstructive jaundice. Subsequently, fine-needle
      aspiration of the pancreatic abscess was performed under ultrasound guidance.
      Enterococcus avium and Klebsiella oxytoca were revealed by culture of abscess
      aspirates. He was successfully cured by treatment with both appropriate
      antibiotic and continuous PTCD for the obstructive jaundice.

PMID- 12522541
TI  - Drug-induced hepatitis with hepatic granuloma due to saridon.
AB  - A 38-year-old Japanese woman with no past history of liver disease developed
      liver dysfunction associated with fever, anorexia, and general malaise following
      the prolonged administration of saridon. A liver biopsy demonstrated multiple
      noncaseating epithelioid granulomas within hepatic lobules, with an inflammatory
      cell infiltrate of the lobular parenchyma and portal tracts. Viral markers and
      autoantibodies were negative. Lymphocyte stimulation tests for saridon and for
      isopropylantipyrine, one of the constituents of saridon, were positive, and
      therefore a diagnosis of drug-induced hepatitis due to administration of saridon
      was made. Her symptoms resolved and liver function test results returned to
      normal following discontinuation of the drug. The possibility of drug-induced
      hepatitis must be considered when liver dysfunction or systemic symptomatology
      develops during saridon therapy.

PMID- 12522542
TI  - Intraductal mucinous tumors occurring simultaneously in the liver and pancreas.
AB  - A case of simultaneous intraductal mucinous tumors of the liver and pancreas in a
      67-year-old man is described. Abdominal ultrasonography and computed tomography
      (CT) revealed the presence of cystic lesions with intraluminal septae both in the
      caudate lobe of the liver and in the uncinate process of the pancreas; these
      cystic lesions communicated with the hepatic duct and pancreatic duct,
      respectively. Mucin retention was observed in the cysts, and cholestasis was
      induced by mucin secretion into the common bile duct. The lesions were resected
      by left hepatic lobectomy with caudate lobectomy, and segmental pancreatectomy.
      Both lesions were multilocular cystic tumors with no papillary projections or
      focal mass effect in their walls. Histologically, both cystic lesions were a
      mixture of hyperplasia and adenoma lined by low papillary columnar epithelium.
      There were no cellular or histological features to suggest malignant change. The
      fibrous intratumor interstitium lacked any mesenchymal or ovarian-like stroma.
      The hepatic lesion was considered to be of a similar nature to intraductal
      papillary mucinous tumor (IPMT) of the pancreas. However, the two lesions
      occurred simultaneously in the liver and pancreas. This case is of interest in
      regard to the diagnosis and management of mucinous hepatopancreatobiliary
      lesions.

PMID- 12522543
TI  - A giant retention cyst of the pancreas (cystic dilatation of dorsal pancreatic
      duct) associated with pancreas divisum.
AB  - We describe a rare case of pancreas divisum associated with a giant retention
      cyst (cystic dilatation of the dorsal pancreatic duct), presumably formed
      following obstruction of the minor papilla. The patient was treated by
      pancreatico(cysto)jejunostomy. A 50-year-old man was admitted with complaints of
      increasing upper abdominal distension and body weight loss. There was no previous
      history of pancreatitis, gallstones, drinking, or abdominal injury. An elastic
      hard tumor-like resistance was palpable in the upper abdomen. Computed tomography
      and ultrasound (US) examinations revealed a giant cystic lesion expanding from
      the pancreas head to the tail. Endoscopic retrograde cholangiopancreatography
      findings showed a looping pancreatic duct which drained only the head and
      uncinate process of the pancreas to the main papilla. A US-guided puncture to the
      cystic lesion revealed that the lesion continued to the main pancreatic duct in
      the tail of pancreas. The lesion was connected to a small cystic lesion, which
      was located inside the minor papilla, and ended there. The amylase level in
      liquid aspirated from the cyst was 37 869 IU/l, and the result of cytological
      examination of the liquid showed class II. A pancreatico(cysto)jejunostomy was
      performed, with the diagnosis being pancreas divisum associated with a retention
      cyst following obstruction of the minor papilla. The histological findings of a
      specimen from the cyst wall revealed that the wall was a pancreatic duct covered
      with mildly inflammatory duct epithelium; there was no evidence of neoplasm. The
      patient is currently well, and a CT examination 2 years after the operation
      showed disappearance of the cyst and normal appearance of the whole pancreas.

PMID- 12522544
TI  - Short-segment Barrett's esophagus associated with high-grade dysplasia.

PMID- 12522545
TI  - Clinical and immunological course in two patients with idiopathic portal
      hypertension.

PMID- 12522546
TI  - The role of inducible nitric oxide synthase in the relaxation of lower esophageal
      sphincter in septic state.

PMID- 12522547
TI  - Health-care workers are at risk of Helicobacter pylori infection.

PMID- 12522548
TI  - How are hepatocytes sensitized to apoptosis?

PMID- 12522549
TI  - Two mismatch repair gene mutations found in a colon cancer patient--which one is
      pathogenic?
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a dominantly inherited
      cancer syndrome. Germline mutations in five different mismatch repair (MMR)
      genes, MSH2, MSH6, MLH1, MLH3, and PMS2 are linked to HNPCC. Here, we describe
      two colon cancer families in which the index patients carry missense mutations in
      both MSH2 and MSH6. The MSH2 mutation, I145M, is the same in both families,
      whereas the MSH6 mutations are different (R1095H and L1354Q). The families do not
      fulfil the international criteria for HNPCC, one family comprising two and the
      other family four colon cancer patients, all in one generation, resembling a
      recessive rather than dominant inheritance characteristic of HNPCC. The tumors of
      the index patients showed microsatellite instability. Functional analysis was
      performed to determine which one of the mutations could primarily underlie the
      cancer susceptibility in the families. MSH2 and MSH6 are known to form a
      heterodimeric complex (MutSalpha) responsible for mismatch recognition. The
      interaction of each mutated protein with its wild-type partner and with its
      mutated partner present in the colon cancer patient, and the MMR function of the
      mutated MutSalpha complexes were determined. Since none of the three mutations
      affected the MSH2-MSH6 interaction or the function of MutSalpha in an in-vitro
      MMR assay, our results suggest that alone the mutations do not cause MMR
      deficiency typical of HNPCC. However, our results do not exclude the possible
      compound pathogenicity of the two mutations.

PMID- 12522550
TI  - Analysis of 15 primary open-angle glaucoma families from Australia identifies a
      founder effect for the Q368STOP mutation of myocilin.
AB  - Primary open-angle glaucoma (POAG) is a leading cause of blindness in the world.
      A number of mutations in the myocilin gene have been identified that predispose
      to glaucoma. The most frequent of these is the Glutamine368STOP (Q368STOP)
      mutation. It has been postulated that individuals with the Q368STOP mutation are
      derived from a common founder. To clarify this situation, we studied 15 unrelated
      POAG families who carried the Q368STOP mutation, from south eastern Australia. In
      one large family, nine affected and ten unaffected individuals were identified
      with the Q368STOP mutation. Closely linked polymorphic microsatellite markers
      were used to establish a disease haplotype in this family. Additional genotyping
      of markers in another 14 unrelated Q368STOP families revealed the presence of the
      same disease haplotype. These findings indicate that the Q368STOP mutation in all
      15 families shared a common origin prior to the European settlement of Australia
      in the early 1800s.

PMID- 12522551
TI  - Neurofibromatosis type 1 gene as a mutational target in a mismatch repair
      deficient cell type.
AB  - DNA mismatch repair (MMR) is the process by which incorrectly paired DNA
      nucleotides are recognized and repaired. A germline mutation in one of the genes
      involved in the process may be responsible for a dominantly inherited cancer
      syndrome, hereditary nonpolyposis colon cancer. Cancer progression in predisposed
      individuals results from the somatic inactivation of the normal copy of the MMR
      gene, leading to a mutator phenotype affecting preferentially repeat sequences
      (microsatellite instability, MSI). Recently, we identified children with a
      constitutional deficiency of MMR activity attributable to a mutation in the h
      MLH1 gene. These children exhibited a constitutional genetic instability
      associated with clinical features of de novo neurofibromatosis type 1 (NF1) and
      early onset of extracolonic cancer. Based on these observations, we hypothesized
      that somatic NF1 gene mutation was a frequent and possibly early event in MMR
      deficient cells. To test this hypothesis, we screened for NF1 mutations in cancer
      cells. Genetic alterations were identified in five out of ten tumor cell lines
      with MSI, whereas five MMR-proficient tumor cell lines expressed a wild-type NF1
      gene. Somatic NF1 mutations were also detected in two primary tumors exhibiting
      an MSI phenotype. Finally, a 35-bp deletion in the murine Nf1 coding region was
      identified in mlh1-/- mouse embryonic fibroblasts. These observations demonstrate
      that the NF1 gene is a mutational target of MMR deficiency and suggest that its
      inactivation is an important step of the malignant progression of MMR-deficient
      cells.

PMID- 12522552
TI  - Genetic heterogeneity of FG syndrome: a fourth locus (FGS4) maps to Xp11.4-p11.3
      in an Italian family.
AB  - FG syndrome (FGS, MIM 305450) is a rare X-linked recessive disorder comprising
      mental retardation and multiple malformations. Various families have been
      described to date, increasing our knowledge of the phenotype variability and
      making the clinical diagnosis complex, especially in sporadic patients. The first
      locus for FG syndrome (FGS1) was linked to chromosome region Xq12-q21.31, but
      other families have been excluded from this locus. The genetic heterogeneity of
      FG syndrome has been confirmed by analysis of an X chromosome inversion
      [inv(X)(q11q28)] in an affected boy and in his mentally retarded maternal uncle,
      suggesting that an additional locus for FG syndrome (FGS2, MIM 300321) is located
      at either Xq11 or Xq28. Recently, a third locus (FGS3) has been mapped to Xp22.3.
      We have identified and clinically characterized an Italian FG family, including
      31 members with three affected males in two generations and two obligate
      carriers. We have excluded linkage to known FGS loci, whereas an extensive study
      of the whole X chromosome has yielded a maximum LOD score (Z(max)) of 2.66
      (recombination fraction=0) for markers between DXS8113 and sWXD805. This new
      locus for FG syndrome corresponds to a region of approximately 4.6 Mb on the X
      chromosome.

PMID- 12522553
TI  - Molecular screening of the TGIF gene in holoprosencephaly: identification of two
      novel mutations.
AB  - Holoprosencephaly (HPE) is the most common severe brain anomaly in humans, which
      results from incomplete cleavage of the forebrain during early embryogenesis. The
      aetiology of HPE is very heterogeneous. Among the genetic factors, TGIF ( TG
      interacting factor), which codes for a transcription factor modulating the
      signalling pathway of TGF-beta, was previously implicated. We investigated 127
      HPE probands by sequencing their TGIF gene and identified the first nonsense
      mutation reported so far and also a novel missense mutation, in two families that
      presented a large range of disease severity. The low number of mutations in TGIF
      suggests that this gene has no major contribution to the aetiology of HPE and our
      study confirms the wide clinical heterogeneity of the disease.

PMID- 12522554
TI  - Characterisation of mutations in 77 patients with X-linked myotubular myopathy,
      including a family with a very mild phenotype.
AB  - X-linked myotubular myopathy is characterised by neonatal hypotonia, muscle
      weakness and respiratory distress in affected males, leading often to early
      death, although prolonged survival is observed in milder forms, or as a result of
      prolongation of ventilation support. It is caused by mutations in the MTM1 gene,
      which encodes a phosphatase called myotubularin, which has been highly conserved
      during evolution, down to yeasts ( S. cerevisiae and S. pombe). To date, 251
      mutations have been identified in unrelated families, corresponding to 158
      different disease-associated mutations, which are widespread throughout the gene.
      We have found additional mutations in 77 patients, including 35 novel ones. We
      identified a missense mutation N180K in a 67-year-old grandfather (the oldest
      known patient with an MTM1 mutation), previously suspected to have autosomal
      centronuclear myopathy, and in his two grandsons also mildly affected. Mild and
      moderate phenotypes associated with novel missense mutations and with a
      translation initiation defect mutation are discussed, as well as severe
      phenotypes associated with particular novel mutations. With the present report,
      192 different mutations in the MTM1 gene have been described in 328 families. The
      spectrum of mutations is now enlarged from the very severe classic neonatal
      phenotype to very mild phenotype allowing survival to the age of 67 years.

PMID- 12522555
TI  - Arrangement of chromosome 11 and 22 territories, EWSR1 and FLI1 genes, and other
      genetic elements of these chromosomes in human lymphocytes and Ewing sarcoma
      cells.
AB  - Standard and repeated fluorescence in situ hybridization and high-resolution
      cytometry were used to study topographical parameters of chromosome 11 and 22
      territories, EWSR1 and FLI1 genes, and other genetic elements of these
      chromosomes in human lymphocytes and Ewing sarcoma cells. HSA 11 and its elements
      (BCL1, FLI1, centromere) were found, on average, more peripherally in comparison
      with HSA 22 and investigated elements (BCR, EWSR1, centromere). After the
      elimination of fluctuations of chromosome territories in nuclear volume, it was
      found that genetic elements in most cases adhered to their territories. The
      investigated genetic elements of HSA 11 were found close to each other relative
      to the large molecular lengths among them. This finding indicates a higher degree
      of chromatin condensation of at least a part of HSA 11 compared with HSA 22. In
      general, there is no correlation between the physical and molecular distance of
      two loci of the same chromosome territory. The topographical parameters of the
      EWSR1 and FLI1 genes do not differ substantially for G(0)-lymphocytes, stimulated
      lymphocytes and Ewing sarcoma cells. The fusion genes pertaining to both
      derivative chromosomes 11 and 22 in Ewing sarcoma cell nuclei are shifted to the
      midway position between the native EWSR1 and FLI1 genes. Comparing results
      obtained for the EWSR1/FLI1 and ABL1/BCR genes in samples of patients suffering
      from Ewing sarcoma or chronic myelogenous leukaemia, it can be concluded that the
      mean positions of the fusion genes are determined by the final structure of the
      chimeric chromosomes and do not depend on the location of the translocation
      event.

PMID- 12522556
TI  - Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2
      cause hearing loss in one family.
AB  - We have ascertained a multi-generation family with apparent autosomal recessive
      non-syndromic childhood hearing loss (DFNB). Failure to demonstrate linkage in a
      genome-wide scan with 300 polymorphic markers has suggested genetic heterogeneity
      for the hearing loss in this family. This heterogeneity could be demonstrated by
      analysis of candidate loci and genes for DFNB. Patients in one branch of the
      family (branch C) are homozygous for the 35delG mutation in the GJB2 gene
      (DFNB1). Patients in two other branches (A and B) carry two new mutations in the
      cadherin 23 ( CDH23) gene (DFNB12). A homozygous CDH23 c.6442G-->A (D2148N)
      mutation is present in branch A. Patients in branch B are compound heterozygous
      for this mutation and the c.4021G-->A (D1341N) mutation. The substituted aspartic
      acid residues are highly conserved and are part of the calcium-binding sites of
      the extracellular cadherin (EC) domains. Molecular modeling of the mutated EC
      domains of CDH23 based on the structure of E-cadherin indicates that calcium
      binding is impaired. In addition, other aspartic and glutamic acid residue
      substitutions in the highly conserved calcium-binding sites reported to cause
      DFNB12 are also likely to result in a decreased affinity for calcium. Since
      calcium provides rigidity to the elongated structure of cadherin molecules
      enabling homophilic lateral interaction, these mutations are likely to impair
      interactions of CDH23 molecules either with CDH23 or with other proteins. DFNB12
      is the first human disorder that can be attributed to inherited missense
      mutations in the highly conserved residues of the extracellular calcium-binding
      domain of a cadherin.

PMID- 12522557
TI  - Two alternative exons can result from activation of the cryptic splice acceptor
      site deep within intron 2 of the dystrophin gene in a patient with as yet
      asymptomatic dystrophinopathy.
AB  - Intron 2 of the dystrophin gene is unusually large, extending 157 kb on the X
      chromosome, and is known to contain one cryptic exon 2a. Here, we report that a
      single nucleotide change in the middle of this huge intron is a source of two
      novel extra exons. A novel point mutation changing T to A nucleotide was
      identified at 5591 bp downstream from the 3' end of exon 2 (T310+5591A) in
      genomic DNA of an asymptomatic dystrophinopathy case. The mutation identification
      was initiated by detection of two novel dystrophin mRNAs containing a 132
      nucleotide or 46-nucleotide insertion between exons 2 and 3 in lymphocytes but
      one with a 132-nucleotide insertion in skeletal muscle. It was concluded that
      T310+5591A created a novel consensus sequence for a splice acceptor site leading
      to the formation of two novel exon structures by using two cryptic splice donor
      sites at 132 bp or 46 bp downstream. The former maintained the dystrophin reading
      frame and was expected to insert 44 amino acids in the N-terminal domain of
      dystrophin, whereas the latter created a premature stop codon. An
      immunohistochemical study of the skeletal muscle of the patient disclosed that
      the N-terminal domain of dystrophin was not stained, but the rod- and C-terminal
      domains were stained in a patchy and discontinuous manner, indicating that the in
      frame mRNA was functional. Creation of a splice acceptor site by a single
      nucleotide change leading to extra exon structures is a novel molecular mechanism
      in human disease.

PMID- 12522558
TI  - Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine,
      vitamin B12, and DNA damage in coronary artery disease.
AB  - Elevated levels of plasma homocysteine (Hcy), a risk factor for coronary artery
      disease (CAD), can result from genetic errors, e.g., the
      methylenetetrahydrofolate reductase (MTHFR) polymorphism, or nutritional
      deficiencies, e.g., in vitamin B12 and folate. The mechanism by which Hcy induces
      atherosclerosis is not fully understood. Recently, Hcy has also been observed to
      induce DNA damage. In this study, we have investigated whether DNA damage is
      related to the C677T variant in the MTHFR gene and to plasma levels of Hcy, B12,
      and folate in patients with CAD. Patients ( n=46) with angiographically proven
      CAD were studied by using the micronucleus (MN) test, an accepted method for
      evaluating genetic instability. TT patients had plasma Hcy levels higher than
      those with the CT or CC genotypes (27.8+/-5.2 vs 13.7+/-2.2 and 12.9+/-1.9 micro
      mol/l, respectively; P=0.02). Patients with multi-vessel disease had higher
      plasma Hcy levels (11.6+/-1.2, 22.0+/-4.7, 19.3+/-3.9 micromol/l for one-, two-
      and three-vessel disease, respectively; P=0.05). The MN index increased with the
      number of affected vessels (8.4+/-0.7, 11.1+/-2.0, 14.2+/-1.7 for one-, two-, and
      three-vessels disease, respectively; P=0.02) and was significantly higher in
      subjects with the TT genotype compared with the CC or CT genotypes (15.7+/-2.4 vs
      8.9+/-1.7 and 9.9+/-0.8; P=0.02). The MN index was also correlated negatively
      with plasma B12 concentration ( r=-0.343; P=0.019) and positively with plasma Hcy
      ( r=0.429, P=0.005). These data indicate that the MN index is associated with the
      severity of CAD and is related to the MTHFR polymorphism, suggesting an
      interesting link between coronary atherosclerosis and genetic instability in
      humans.

PMID- 12522559
TI  - Molecular study of a new family with hereditary renal cell carcinoma and a
      translocation t(3;8)(p13;q24.1).
AB  - An alternative model has been proposed for the development of clear-cell renal
      cell carcinoma (RCC) in families where chromosome 3 translocations segregate with
      the disease. In this model, the existence of a translocation involving chromosome
      3 would favour the non-disjunctional loss of the derivative chromosome carrying
      the 3p segment. Additionally, subsequent somatic mutations in the VLH gene,
      located in 3p25-26, would inactivate this tumour suppressor gene. In the present
      work, we describe a new family with two clear-cell RCC affected members and a
      t(3;8)(p13;q24.1) translocation in two consecutive generations. We observed loss
      of the derivative chromosome carrying the 3p segment (der(8)) and somatic
      mutation of the VHL gene in the left-kidney tumoral tissue of the proband. His
      right-kidney tumour carried a different VHL mutation and loss of heterozygosity
      (LOH) was not detected. The mother of the proband was also clear-cell RCC
      affected but the tumoral tissue analysed did not carry any VHL gene mutations.
      Another member of the family, a maternal aunt, had a papillary RCC and did not
      carry this translocation, the LOH on 3p or the VHL somatic mutations. Haplotype
      analysis of the three affected members revealed that they did not inherit a
      common region on 3p, confirming the different genetic origin of both tumour
      types. Finally, the presence of RCC in other non-available members of the family
      highlights the overall risk for RCC in families with chromosome 3 translocations.
      In the present work, we have confirmed the proposed mechanism for the development
      of clear-cell RCC in this family, although we cannot discard the existence of
      other genes, in addition to VHL, being involved in hereditary RCC.

PMID- 12522560
TI  - Chloride channel 7 (CLCN7) gene mutations in intermediate autosomal recessive
      osteopetrosis.
AB  - Osteopetrosis is a heterogeneous group of inherited disorders that includes a
      malignant autosomal recessive form, an intermediate autosomal recessive form and
      autosomal dominant forms of the disease. Most malignant osteopetroses have been
      ascribed to mutations in the OC116 gene encoding the human a3 subunit of vacuolar
      H(+)-ATPase. Few cases of autosomal recessive malignant osteopetrosis have been
      ascribed to mutations in the chloride channel 7 gene (CLCN7), which accounts for
      all autosomal dominant type II cases reported to date. Up until now, however,
      nothing has been known regarding the molecular basis of the intermediate form of
      osteopetrosis (IARO). Our study of two Portuguese IARO families shows that
      homozygosity for ClCN7 mutations also accounts for this form of osteopetrosis.
      The two patients presented with spontaneous fractures in the first years of life
      and generalised increase of bone density. Direct sequencing of the ClCN7 gene in
      both patients revealed homozygosity for two mutations (G203D and P470Q). We
      conclude therefore that ClCN7 mutations not only account for some dominant and
      malignant forms but also for intermediate forms of osteopetrosis.

PMID- 12522561
TI  - Mutational analysis in longest known survivor of mucopolysaccharidosis type VII.
AB  - Mucopolysaccharidosis VII (MPS VII) is an autosomal recessive disorder caused by
      the deficiency of beta-glucuronidase leading to the intralysosomal storage of
      heparan, dermatan, and chondroitin sulfate. Here, we report the identification of
      two novel missense mutations K350N and R577L in a 37-year-old patient with beta
      glucuronidase deficiency and a relatively mild MPS VII phenotype. Expression of
      the K350N mutation in baby hamster kidney cells has revealed residual enzymatic
      activity and normal transport of the enzyme to the lysosome. However, expression
      of the R577L or the double mutant K350N/R577L results in rapid degradation of the
      enzyme in early biosynthetic compartments and a total loss of enzymatic activity.
      We attribute the mild phenotype to the residual catalytic activity provided by
      the K350N mutant. At the time of her death at the age of 37 years, this patient
      was the longest known survivor with MPS VII.

PMID- 12522562
TI  - Maternal aging and chromosomal abnormalities: new data drawn from in vitro
      unfertilized human oocytes.
AB  - The effect of maternal age on the incidence of chromosomal abnormalities was
      investigated on a large sample of 3,042 in vitro unfertilized human oocytes II
      obtained from 792 women aged 19-46 years and participating in an in vitro
      fertilization program for various indications. The chromosomal analysis combined
      a gradual fixation of oocytes and an adapted R-banding technique. A total of
      1,397 interpretable karyotypes were obtained. Various types of numerical
      aberration were observed, involving conventional chromosome nondisjunction
      (3.5%), single-chromatid nondisjunction (5.9%), complex (0.8%) or extreme
      aneuploidy (0.5%), diploidy (5.4%), and set of single chromatids (3.8%). No
      significant difference was found in the mean age of women according to the
      various types of chromosomal abnormalities. A positive relationship was found
      between maternal age and the global rate of aneuploidy, in agreement with the
      findings of epidemiological studies. The incidence of both whole-chromosome
      nondisjunction and precocious chromatid separation were correlated to maternal
      aging but the most significant correlation was found between maternal aging and
      single-chromatid nondisjunction. The rate of diploidy was also correlated to a
      slight extent to maternal aging, whereas no correlation was found between
      maternal age and the rate of single-chromatid sets. These data reveal that single
      chromatid malsegregation is an essential factor in the age-dependent occurrence
      of nondisjunction in human oocytes. Disturbance in sister-chromatid cohesion
      might be a causal mechanism predisposing to premature chromatid separation and
      subsequently to nondisjunction in female meiosis.

PMID- 12522563
TI  - Maternal serum cell-free fetal DNA levels are increased in cases of trisomy 13
      but not trisomy 18.
AB  - Cell-free fetal DNA in the maternal circulation is a potential noninvasive marker
      for fetal aneuploidies. In previous studies with Y DNA as a fetal-specific
      marker, levels of circulating fetal DNA were shown to be elevated in women
      carrying trisomy 21 fetuses. The goal of this study was to determine whether cell
      free fetal DNA levels in the serum of pregnant women carrying fetuses with
      trisomies 13 or 18 are also elevated. Archived maternal serum samples from five
      cases of male trisomy 13 and five cases of male trisomy 18 were studied. Each
      case was matched for fetal gender, gestational age, and duration of freezer
      storage to four or five control serum samples presumed to be euploid after
      newborn medical record review. Real-time quantitative polymerase chain reaction
      amplification of DYS1 was performed to measure the amount of male fetal DNA
      present. Unadjusted median serum fetal DNA concentrations were 97.5 GE/ml
      (genomic equivalents per milliliter; 29.2-187.0) for the trisomy 13 cases, 31.5
      GE/ml (18.6-77.6) for the trisomy 18 cases, and 40.3 GE/ml (3.7-127.4) for the
      controls. Fetal DNA levels in trisomy 13 cases were significantly elevated (
      P=0.016) by analysis of variance of the ranks of values within each matched set.
      In contrast, fetal DNA levels in trisomy 18 cases were no different from the
      controls ( P=0.244). Second trimester maternal serum analytes currently used in
      screening do not identify fetuses at high risk for trisomy 13. Fetal DNA may
      facilitate noninvasive screening for trisomy 13 provided that a gender
      independent fetal DNA marker can be developed.

PMID- 12522564
TI  - Fine structure mapping of CIAS1: identification of an ancestral haplotype and a
      common FCAS mutation, L353P.
AB  - Familial cold autoinflammatory syndrome (FCAS) is an autosomal dominant
      inflammatory disease with a high degree of penetrance that is characterized by
      episodes of rash, arthralgia, fever, conjunctivitis, and leukocytosis after
      generalized exposure to cold. FCAS was previously mapped to a 10-cM region on
      chromosome 1q44, and subsequently the gene ( CIAS1) responsible for FCAS was
      identified. In this paper, we describe the physical and genetic mapping of the
      FCAS locus, and we report a large ancestral haplotype and a new disease-causing
      mutation. A BAC contig of approximately 3 Mb was developed and subsequently used
      for high throughput sequencing. We identified a critical region of 4 cM using
      rare crossover events in four large North American FCAS families. An unusually
      large shared haplotype (40 cM) was identified in three of the four families. We
      found a single heterozygous missense mutation (T1058C=L353P) in exon 3 of CIAS1
      in all four families that is responsible for the large majority of FCAS cases
      described in the literature. We also report a comprehensive list of intragenic
      single nucleotide polymorphisms. The data provided here will assist others
      researching the 1q44 region and will aid clinicians in the diagnosis of FCAS.

PMID- 12522565
TI  - Several interacting genes influence the malignant hyperthermia phenotype.
AB  - Malignant hyperthermia (MH), a potentially lethal disorder of skeletal muscle
      calcium homeostasis, manifests only on exposure to certain anaesthetic drugs. The
      mode of inheritance appears to be autosomal dominant with both locus and allelic
      heterogeneity having been reported. Association analysis of eight MH candidate
      loci in UK families has indicated that several genes influence susceptibility in
      individual families, rather than MH simply being a major gene defect. In support
      of this hypothesis, we present data on a replica analysis of an independent
      sample of European MH families.

PMID- 12522566
TI  - Spectrum of phenotypes and genotypes in Parkinson's disease.
AB  - The pathogenesis of Parkinsons disease (PD) is currently unknown. Environmental
      and genetic factors might contribute to the neurodegenerative process. Genetic
      mapping approaches in rare familial cases with autosomal recessive and autosomal
      dominant inheritance of PD suggest wide genetic heterogeneity of the disease.
      These gene loci in turn allow now a more specific clinical investigation of
      affected families to study the clinical heterogeneity of PD. The recent
      identification of mutations in three genes involved in protein degradation and
      aggregation in familial PD does now facilitate the deciphering of other genes
      involved in the pathogenesis of the disease.

PMID- 12522567
TI  - Neuroprotection in idiopathic Parkinson's disease.
AB  - Neuroprotection may be defined as measures to protect neurons from degenerative
      processes by use of medication, to stop or prolong cell death and to positively
      interfere with the underlying cell death mechanism(s) in Parkinson's disease. So
      far, the question whether neuroprotection exists in parkinsonian treatment was
      difficult to answer because we had no objective method to check for dopaminergic
      cell death. Imaging techniques such as beta-CIT-SPECT or F-Dopa-PET are the best
      methods to approach this goal. This paper critically reviews the two most
      recently published studies on the possible neuroprotective effect of the dopamine
      agonists pramipexole and ropinirole. For the first time, these two drugs have
      shown a significantly smaller decrease in dopamine cell function when compared to
      levodopa. Nonetheless, there may still be some hesitation to accept the good
      correlation between imaging techniques and dopamine cell function. For obvious
      reasons, neither study included a placebo arm, since ethical reasons forbid a
      period of 2 to 4 years without treatment. Thus, the question, whether these two
      dopamine agonists are really neuroprotective or whether levodopa increases cell
      death in Parkinson's disease has to stay open. A rather remarkable finding was
      that, in both studies, motor function was slightly better in the levodopa arm,
      which raises the question whether imaging techniques really reflect improvement
      in cell function in those patients treated with dopamine agonists. We certainly
      have to continue our search for even better tools to evaluate neuroprotection.

PMID- 12522568
TI  - Drug interactions in the treatment of Parkinson's disease.
AB  - In recent years, the antiparkinsonian drug regime has become increasingly
      complicated. A wide range of antiparkinson agents is meanwhile available.
      Combination therapies may unfortunately induce interactions up to the point of
      life-threatening events. The potential of drug-drug interactions must be taken
      into account before starting a patient on combination treatment. Moreover, the
      frequent multimorbidity of patients with Parkinson's disease necessitates the
      application of additional drugs. A general overview is difficult to maintain
      because of the countless number of possible interactions. Cautious proceeding is
      certainly indicated in particular cases. The most common interactions will be
      discussed below. We should bear in mind that many of the interactions related to
      drug combinations are unknown yet.

PMID- 12522569
TI  - Neural stem cells and Parkinson's disease.
AB  - The discovery that embryonic stem cells, neural stem cells and potentially
      mesenchymal stem cells bear the potential to differentiate into neurons and glia
      in vitro and in vivo has opened a rapidly growing scientific field. Current
      research is very likely to impose a major impact on diagnosis and treatment of a
      variety of neuropsychiatric disorders. One of the paramount immediate goals of
      stem cell research is to develop tissue sources for restorative treatment of
      patients with Parkinson's disease. We have been able to develop predopaminergic
      cells derived from human embryonic or fetal midbrain that have been amplified in
      vitro for more than 2 years. These cells will hopefully enable restorative
      treatment of patients with Parkinson's disease in the near future.

PMID- 12522570
TI  - Current state of stem cell research for the treatment of Parkinson's disease.
AB  - Current findings suggest that multipotent stem cells may be suitable for cell
      replacement therapies in the treatment of neurodegenerative disorders. Embryonic
      stem (ES) cells are pluripotent cells isolated from the inner cell mass of the
      preimplantation blastocyst, which give rise to all cells in the organism.
      Similarly, multipotent stem cells are also able to regenerate, but are believed
      to have a more restricted potential than ES cells, and are often defined by the
      organ from which they are derived. Neural stem cells have been categorized as
      multipotent stem cells derived from the nervous system with the capacity to
      regenerate and to give rise to cells belonging to all three cell lineages in the
      nervous system: neurons, oligodendrocytes, and astrocytes. It is hoped that
      research on stem cells may reveal methods for producing an infinite supply of
      dopamine neurons for transplant into Parkinson's disease (PD) patients. The
      problem is controlling cell growth and differentiation. We will briefly review
      the current state of stem cell research and will critically discuss the potential
      of stem cells for the treatment of PD.

PMID- 12522571
TI  - Deep-brain stimulation for Parkinson's disease.
AB  - Deep brain simulation (DBS) is a powerful new therapeutic approach for patients
      with Parkinson's disease. However, patient selection is critical for a valuable
      therapeutic result. Dopa sensitivity of the target symptoms, severe disability
      and low neurosurgical risks are among the major criteria for this indication.
      Other criteria like age or cognition must still be addressed in future
      prospective studies. The preferred target for DBS in PD is the subthalamic
      nucleus for various good reasons. However, prospective studies for this procedure
      are lacking and some clinical problems may be more easily solved with targeting
      the internal pallidum or the thalamus. Despite major progress in this field, much
      work remains to be done.

PMID- 12522572
TI  - Early diagnosis of Parkinson's disease.
AB  - In idiopathic Parkinson's disease (IPD) approximately 60 % of the nigrostriatal
      neurons of the substantia nigra (SN) are degenerated before neurologists can
      establish the diagnosis according to the widely accepted clinical diagnostic
      criteria. It is conceivable that neuroprotective therapy starting at such an
      'advanced stage' of the disease will fail to stop the degenerative process.
      Therefore, the identification of patients at risk and at earlier stages of the
      disease appears to be essential for any successful neuroprotection. The discovery
      of several genetic mutations associated with IPD raises the possibility that
      these, or other biomarkers, of the disease may help to identify persons at risk
      of IPD. Transcranial ultrasound have shown susceptibility factors for IPD related
      to an increased iron load of the substantia nigra. In the early clinical phase, a
      number of motor and particularly non-motor signs emerge, which can be identified
      by the patients and physicians years before the diagnosis is made, notably
      olfactory dysfunction, depression, or 'soft' motor signs such as changes in
      handwriting, speech or reduced ambulatory arm motion. These signs of the early,
      prediagnostic phase of IPD can be detected by inexpensive and easy-to-administer
      tests. As one single instrument will not be sensitive enough, a battery of tests
      has to be composed measuring independent parameters of the incipient disease.
      Subjects with abnormal findings in this test battery should than be submitted to
      nuclear medicine examinations to quantify the extent of dopaminergic injury and
      to reach the goal of a reliable, early diagnosis.

PMID- 12522573
TI  - Which factors influence therapeutic decisions in Parkinson's disease?
AB  - Development of dyskinesia is a common phenomenon during the long-term course of
      Parkinson's disease. During the last few years, some but not all pathogenetic
      mechanisms causing dyskinesias in PD have become better understood. Severity of
      Parkinson's disease and levodopa dosing are the main clinical risk factors. Most
      concepts underline the significance of pulsatile D1-receptor stimulation for the
      development of dyskinesias. The interactions between D1- and D2-mediated STR-Gpi
      pathways and colocalized neuropeptides are important but not fully understood.
      Glutamatergic overactivity might also be a significant pathogenetic factor.
      According to these pathophysiological concepts, therapeutic strategies focus
      mainly on continuous postsynaptic DA-receptor stimulation by long-acting DA
      agonists or highly selective D2-agonists. Another strategy is the use of NMDA
      antagonists.

PMID- 12522574
TI  - Practical importance of neuroprotection in Parkinson's disease.
AB  - Consensus could be reached that there is overwhelming evidence of preclinical
      neuroprotection. However, the evidence of neuroprotection/neurorescue under
      clinical conditions is limited. Lessons from clinical trials designed to show
      neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with
      the drugs available neuroprotection/neurorescue has to start as early as
      possible. A PET-controlled clinical trial with ropinirole shows that there seems
      to be a good chance for neuroprotection in the early phase of Parkinson's disease
      in patients treated from the very beginning of the disease while there is no such
      benefit in patients with a late start of a neuroprotective therapeutic strategy.
      Also long-term clinical neuroprotection cannot be reached. Complicating factors
      to demonstrate clinical neuroprotection are discussed.

PMID- 12522575
TI  - Quantitative analysis of bikunin-laden mast cells in follicular eruptions and
      chronic skin lesions of atopic dermatitis.
AB  - Bikunin, an inhibitor of serine proteases, is widely distributed in human
      tissues, including the skin, and may inhibit tryptase and modulate allergic
      inflammation. The purpose of the present study was to compare follicular
      eruptions (FE), so-called atopic skin or perifollicular accentuation, with atopic
      dermatitis (AD) lesions (ADL) by immunohistochemical analysis using antibodies to
      bikunin and tryptase. Immunohistochemically, bikunin was colocalized with
      tryptase in dermal mast cells, and a small quantity of bikunin was also deposited
      in the intercellular spaces in FE and ADL. The number of bikunin-laden mast cells
      per 0.78 mm(2) of skin was 78.1+/-7.1 (mean+/-SEM, n=14) in FE, 25.4+/-2.3 (n=10)
      in normal skin from children and infants, 91.3+/-11.8 (n=10) in ADL, 25.6+/-4.8
      (n=5) in nonlesional skin of AD, and 27.8+/-2.0 (n=13) in normal adult skin. The
      difference between FE and normal control skin from children and infants, between
      FE and nonlesional skin of AD, and between lesional and nonlesional skin of AD
      were significant. Based on the above findings and the occasional presence of
      spongiosis and lymphocyte infiltration, in FE moderate inflammation is apparent
      histopathologically even though little inflammation is apparent clinically.

PMID- 12522576
TI  - Expression of serotonin receptors in allergic contact eczematous human skin.
AB  - The expression of the serotonin (5-HT) receptors 5-HT1AR, 5-HT2AR and 5-HT3R was
      investigated in allergic contact eczematous human skin by an indirect
      fluorescence method. 5-HT1AR expression was found in basal epidermal NK1-beteb
      positive cells, which were more elongated and showed longer dendritic processes
      in contact eczematous skin than in control skin. Immunoreactivity for 5-HT1AR was
      also found in the upper part of the epidermis, with no difference between
      eczematous and control skin. 5-HT1AR expression was also found in 33.3+/-6.5% and
      63.7+/-11.3% of papillary dermal mononuclear cells in inflamed skin and control
      skin, respectively ( P<0.001), as well as in vessel walls. Some of these
      mononuclear cells were tryptase-positive, and found in both eczematous and
      control skin. 5-HT2AR-positive cells were found in the upper part of the
      epidermis in eczematous skin, but were more evenly distributed in the epidermis
      of control skin. In addition, inflammatory dermal mononuclear cells and vessel
      walls showed immunoreactivity for this receptor. 5-HT3R expression was found in
      the basal epidermal layer of eczematous and control skin. These findings indicate
      a plasticity in the effects of serotonin, especially regarding 5-HT1AR, in
      allergic contact eczematous skin.

PMID- 12522577
TI  - Fumaric acid esters are potent immunosuppressants: inhibition of acute and
      chronic rejection in rat kidney transplantation models by methyl hydrogen
      fumarate.
AB  - The effectiveness and safety of fumaric acid esters (FAEs) for the treatment of
      psoriasis has been demonstrated. Their mode of action, however, is poorly
      understood. To determine the immunomodulatory potential of calcium methyl
      hydrogen fumarate (CaMHF) in transplant models, we tested the compound in rat
      transplantation models of acute rejection (AR) and chronic rejection (CR).
      Orthotopic kidney transplantation was combined with contralateral nephrectomy
      using the strain combinations WF to BDIX (AR) and F344 to LEW (CR). Recipients
      were treated orally prophylactically (day -28 to day +28, AR and CR model) or
      therapeutically (day +30 to day +60, CR model). CaMHF significantly prolonged the
      time to onset of AR in the WF/BDIX model. The half-lives of the grafts were 14
      days in the CaMHF group, 7 days in the placebo-treated control group and 9 days
      in the untreated control group ( P<0.01). Three of ten CaMHF-treated rats showed
      permanent graft acceptance (defined as survival for >100 days) resulting in a
      mean survival time of >42.3+/-41.0 ( P<0.01) in comparison with >28.3+/-38.3 days
      in the placebo-treated group and 9.4+/-2.6 days in the untreated control group.
      In the F344/LEW model of chronic graft injury, only prophylactic CaMHF treatment
      significantly inhibited the development of CR ( P=0.001; mean survival times
      >28.4+/-2.0 weeks, >23.9+/-6.0 weeks and >21.1+/-5.4 weeks in the prophylactic
      CaMHF, therapeutic CaMHF, and placebo group, respectively). By 30 weeks six of
      ten prophylactically treated animals were still alive, but only three of nine and
      one of ten were alive in the therapeutically treated and placebo-treated groups,
      respectively ( P<0.05). These findings indicate that CaMHF treatment effectively
      inhibits AR and CR, and demonstrates marked in vivo immunomodulatory efficacy.
      Thus, FAEs should be considered as drugs showing considerable immunosuppressive
      efficacy. This might have implications with regard to safety issues (e.g. immune
      monitoring) and novel potentially suitable indications (e.g. transplantation and
      other immune diseases).

PMID- 12522578
TI  - Production of matrix metalloproteinase 2 in fibroblast reaction to mechanical
      stress in a collagen gel.
AB  - The reaction of fibroblasts to mechanical forces generated by fibroblasts
      themselves in anchored collagen lattices was studied. Fibroblasts were cast in
      collagen gels. Free retracted gels (RG) were compared with stressed gels (SG) in
      3-day and 14-day experiments. As previously described, SG showed an increase in
      protein, mainly collagen, biosynthesis. Matrix metalloproteinases (pro-MMP-2 and
      MMP-2) were studied by zymography. Certain cell membrane components, integrin
      alpha(2) and phosphatidylserine, were studied by flow cytometry with antibodies
      against the integrin alpha(2) subunit and with annexin V binding. Mechanical
      stress stimulated production of pro-MMP-2 both in the short-term (3-day) and the
      longer term (14-day) cultures. However, the pro-enzyme was not more activated and
      there was no difference in the amount of MMP-2 between RG and SG. There was only
      an increase with time under both conditions. The stressed fibroblasts reacted
      early with an increase in the integrin alpha(2) subunit, but the stimulated cells
      disappeared from the 14-day cultures. The number of cells measured in terms of
      the amount of DNA decreased between day 3 and day 14, mainly in the SG due to
      cytolysis. This cell stress was related to an alteration in the plasma membrane
      detected by the annexin V marker.

PMID- 12522579
TI  - Identification of calcium-induced genes in HaCaT keratinocytes by polymerase
      chain reaction-based subtractive hybridization.
AB  - Suppression subtractive hybridization, a PCR-based method for cDNA subtraction,
      was used to identify differentially expressed genes in keratinocytes.
      Differentiation was induced by elevating the calcium level in the cell culture
      medium. Using HaCaT immortalized keratinocytes cultured in the presence of a high
      calcium concentration, we isolated 60 clones representing 48 different genes. By
      reverse Northern analysis, 13 genes were scored as overexpressed in these HaCaT
      cells. Northern blot analysis was used to confirm differential gene expression.
      Six genes, keratin 1, plasminogen activator inhibitor type 2 (PAI-2), ferritin H,
      peroxiredoxin 5 (PRDX5), insulin-like growth factor binding protein-3 (IGFBP-3),
      and one EST gene, were differentially expressed in HaCaT cells cultured in the
      presence of a high calcium concentration. Two of these genes, keratin 1 and PAI
      2, are differentially expressed during keratinocyte terminal differentiation.
      IGFBP-3, which has reduced expression during epidermal differentiation, was
      increased after culture in a high-calcium medium for 2 or 5 days. Overexpression
      of the ferritin H and PRDX5 genes due to elevated calcium has not been reported
      in keratinocytes. We demonstrated the expression of IGFBP-3, ferritin H, PRDX5,
      and one gene of a matching sequence from the EST database during differentiation
      in primary cultured normal human keratinocytes. The EST gene expressed two
      transcripts of 1.8 kb and 2.5 kb in HaCaT cells, and the transcripts were
      confirmed to increase in keratinocytes cultured in a high-calcium medium.

PMID- 12522580
TI  - Differential activation of nuclear factor kappa B subunits in a skin dendritic
      cell line in response to the strong sensitizer 2,4-dinitrofluorobenzene.
AB  - Dendritic cell (DC) maturation is essential for the initiation of T-dependent
      immune responses. Nuclear factor kappa B (NF-kappaB) transcription factors are
      ubiquitously expressed signalling molecules, known to regulate the transcription
      of a large number of genes involved in immune responses, including cytokines and
      cell surface molecules. In this work, we studied the time-dependent activation of
      five members of the NF-kappaB family, p50, p52, p65, RelB and cRel, in a mouse
      skin DC line in response to stimulation with the strong sensitizer, 2,4
      dinitrofluorobenzene (DNFB). Western blot assay revealed that exposure of fetal
      skin DC (FSDC) to DNFB induced the degradation of the inhibitor of NF-kappaB
      (IkappaB). Three out of its five members, i.e. p50, p52, and RelB, were similarly
      activated upon DNFB stimulation, with subsequent translocation of these subunits
      from the cytosol to the nucleus, but with different kinetics. In contrast, p65
      expression was diminished in both the nucleus and the cytosol. The
      electrophoretic mobility shift assay (EMSA) showed that exposure of FSDC to DNFB
      induced DNA binding to NF-kappaB. Together, these results show that DNFB
      differentially activates the various members of the NF-kappaB family in skin DC.

PMID- 12522581
TI  - Lithium chloride increases pigmentation of melanoma cells by interfering with the
      inositol phosphate pathway.

PMID- 12522583
TI  - An overview of holistic medicine and complementary and alternative medicine for
      the prevention and treatment of BPH, prostatitis, and prostate cancer.
AB  - An accumulating body of scientific evidence supports the notion that a holistic
      outlook on health and life and complementary and alternative medicine health
      practices can promote wellness and prevent and treat prostate disease. This
      overview explores some of the fundamental philosophical, diagnostic, and
      therapeutic differences between conventional and holistic medicine, and discusses
      how to integrate evidence-based complementary and alternative medicine, holistic
      medicine, and conventional medicine for the prevention and treatment of prostate
      disease.

PMID- 12522582
TI  - Complementary medicine in urology - a different approach.

PMID- 12522584
TI  - Botanical medicines for the urinary tract.
AB  - Four important categories of urologic herbs, their history, and modern scientific
      investigations regarding them are reviewed. Botanical diuretics are discussed
      with a focus on Solidago spp (goldenrod) herb, Levisticum officinale (lovage)
      root, Petroselinum crispus (parsley) fruit, and Urtica dioica (stinging nettle)
      herb. Urinary antiseptic and anti-adhesion herbs, particularly Arctostaphylos uva
      ursi (uva-uri) leaf, Juniperus spp (juniper) leaf, and Vaccinium macrocarpon
      (cranberry) fruit are reviewed. The antinephrotoxic botanicals Rheum palmatum
      (Chinese rhubarb) root and Lespedeza capitata (round-head lespedeza) herb are
      surveyed, followed by herbs for symptoms of benign prostatic hyperplasia, most
      notably Serenoa repens (saw palmetto) fruit, Urtica dioica root, and Prunus
      africana (pygeum) bark.

PMID- 12522585
TI  - A complementary approach to urolithiasis prevention.
AB  - About one-half million adults in the United States experience a renal stone each
      year, about two hundred thousand of whom are hospitalized; the lifetime incidence
      of renal stones in men is about ten percent. Risk factors for stone formation
      include a positive family history, nutritional factors (excessive intake of
      animal protein, fat, sugar, oxalates, colas, alcohol, caffeine, salt, and vitamin
      D), nutritional deficiencies (water, magnesium, calcium, potassium, and vitamin
      B6), lifestyle factors (physical inactivity and problematic pharmaceuticals), and
      associated disease states (osteoporosis, parathyroid problems, osteoporosis, gout
      and recurrent urinary tract infections). The chemical makeup of the stone is
      important since prevention of recurrences varies somewhat depending on the type
      of stone involved. The outline of preventive steps holds the potential for
      preventing recurrence in the vast majority of cases.

PMID- 12522586
TI  - Role of behavioral changes and biofeedback in urology.
AB  - Voiding disorders are common in urological patients. Pelvic floor dysfunction may
      result from overtraining pelvic floor muscles in an attempt to prevent leaking.
      This can further cause bladder dysfunction or weakening the pelvic floor muscles.
      Pelvic floor dysfunction or insufficient relaxation of the pelvic floor results
      in hesitancy, intermittency, and high postvoid residuals (PVR). Behavioral
      changes and biofeedback play a key role in urologic problems including pelvic
      pain, irritative voiding symptoms, recurrent urinary tract infections, and
      incontinence. Biofeedback involves using electrodes to transduce muscle
      potentials into auditory or visual signals; patients learn to increase or
      decrease voluntary muscle activity. Conservative behavioral and biofeedback
      treatments are safe and effective interventions that should be more readily
      available to patients as a first-line treatment for voiding dysfunction. Patient
      education may take time but has higher long-term success and makes the patient
      more responsible and less passive regarding their condition.

PMID- 12522587
TI  - Hatha Yoga therapy management of urologic disorders.
AB  - Hatha Yoga (often referred to as "yoga") is an ancient type of physical and
      mental exercise that has been used as a therapeutic modality in traditional
      Indian medicine for centuries. Yoga as a complementary modality in western
      medicine is more recent and continues to grow. Chronic urologic disorders are
      often difficult to diagnose because their presentation mimic other medical
      conditions and are often a diagnosis of exclusion. Treatment is also frustrating
      because the more traditional treatments are often unsuccessful in managing
      chronic disorders. Health care practitioners are often forced to look elsewhere
      for other modalities to provide pain relief and improve quality of life. Hatha
      Yoga is one of these modalities which has been extremely useful to many patients
      in reducing the suffering seen with chronic urologic conditions such as:
      prostatodynia, chronic orchitis, chronic epididymitis, vulvodynia, interstitial
      cystitis, etc.

PMID- 12522588
TI  - Interstitial cystitis, pelvic pain, and the relationship to myofascial pain and
      dysfunction: a report on four patients.
AB  - Treatment of chronic pelvic pain (CPP), interstitial cystitis (IC),
      prostatodynia, and irritative voiding symptoms can be frustrating for both
      patients and physicians. The usual approaches do not always produce the desired
      results. We found that when we treated myofascial trigger points (TrP) in pelvic
      floor muscles as well as the gluteus, piriform, infraspinatus, and supraspinatus
      muscles, symptoms improved or resolved. Various palpation techniques were used to
      isolate active myofascial TrPs in these muscles of four patients with severe CPP,
      IC, and irritative voiding symptoms. Injection and stretch techniques for these
      muscles were performed. Visual twitch responses at the skin surface and in the
      muscles were used to verify successful needle piercing of a TrP. The patients
      were asked to verbally describe exactly where the flash of distant pain was felt,
      a process that permitted an accurate recording of the precise pattern of pain
      referred by that TrP. The findings involved with the four patients substantiate
      the need for myofascial evaluation prior to considering more invasive treatments
      for IC, CPP, and irritative voiding symptoms. Referred pain and motor activity to
      the pelvic floor muscles (sphincters), as well as to the pelvic organs, can be
      the sole cause of IC, CPP, and irritative voiding dysfunction and certainly needs
      further investigation.

PMID- 12522589
TI  - The role of acupuncture in the treatment of urologic conditions.
AB  - Although acupuncture is a primary treatment for urologic disorders in China, this
      is not always the case throughout the world. The purpose of this paper is to
      expose the benefits of acupuncture as both a primary and complementary treatment.
      Specific treatments for multiple urologic conditions are presented in this paper
      as a guideline. It is important to realize that there are additional useful
      treatments that belong to other acupuncture types and traditions. In our
      experience, acupuncture has been a useful treatment modality for urologic
      conditions. Patients have responded positively, having choices in their treatment
      with a modality that is associated with minimal side effects and knowing that
      traditional urologic treatments are available if needed.

PMID- 12522590
TI  - An isolated fourth ventricle in neurosarcoidosis: MRI findings.
AB  - We report on an isolated enlargement of the fourth ventricle in a patient with
      neurosarcoidosis which developed 3 years after the insertion of a ventriculo
      atrial shunt. Repeated MRI images were obtained in a patient with known
      neurosarcoidosis between 1995 and 2000. Imaging findings were correlated to the
      medical course of the patient, who developed a hydrocephalus and a trapped fourth
      ventricle consecutively. The isolation was presumably due to granulomatous
      inflammation of the ependyma surrounding the fourth ventricular outlets. The
      isolated fourth ventricle was responsible for a deterioration of neurological
      status. Neurosarcoidosis is a severe complication in sarcoidosis patients. An
      isolated enlargement of the fourth ventricle is a rare complication in clinically
      deteriorated patients with neurosarcoidosis and ventricular drainage, which may
      require neurosurgical treatment.

PMID- 12522591
TI  - MRI demonstration of orbital lipolysis in anorexia nervosa.
AB  - The purpose of this article is to describe the orbital changes due to lipolysis
      in anorexia nervosa. We examined a cachectic patient with MR imaging using T1
      weighted images before and after contrast enhancement. Orbital fat edema has been
      observed in extreme forms of cachexia and the CT and MR findings have recently
      been reported. The imaging appearances have been explained by the disappearance
      of the fat tissue and the appearance of edema due to a disturbance in the
      electrolyte fluid balance. In the recent literature particular attention has been
      paid to the increased lipid peroxidation and lipolysis in anorexia nervosa. These
      metabolic processes result in an increased permeability of the vessel wall
      endothelium, which can explain the extravasation of the contrast agent in the
      orbital fat on MR imaging.

PMID- 12522592
TI  - Primary solitary intracranial melanoma in the sylvian fissure: MR demonstration.
AB  - We present a rare case of a primary intracranial melanoma originating from
      leptomeningeal melanoblasts in the sylvian fissure. The mass appeared
      hyperintense on T1-weighted MR images and hypointense on T2-weighted MR images,
      reflecting the presence of abundant melanin granules in the tumor. Associated
      leptomeningeal enhancement suggested a dire prognosis.

PMID- 12522593
TI  - Tentorial and dural calcification with tertiary hyperparathyroidism: a rare
      entity in chronic renal failure.
AB  - A case of rare calcification of the tentorium cerebelli, the thoracal dura mater
      of the spine, and the sclera in an adult male patient with tertiary
      hyperparathyroidism is presented. The often reported feature in the skull is that
      of a combination of osteopenia and osteosclerosis giving a granular bone texture.
      Extensive dura calcification with this condition has very rarely been reported.
      It is the aim of this paper to document the latter in a patient with chronic
      renal failure and tertiary hyperparathyroidism.

PMID- 12522594
TI  - Moyamoya disease associated with an anterior inferior cerebellar artery arising
      from a persistent trigeminal artery.
AB  - The authors present a case of moyamoya disease associated with a persistent
      trigeminal artery from which the anterior inferior cerebellar artery arose. We
      reviewed previously reported cases of moyamoya disease associated with persistent
      carotid-basilar arterial anastomosis and investigated the embryology of this rare
      arterial variation.

PMID- 12522595
TI  - Aneurysmal re-rupture during selective cerebral angiography.
AB  - Two cases of aneurysmal re-rupture during intracranial angiography are presented.
      This event is accompanied by disastrous consequences with regard to the clinical
      condition of the patient, as is evident from the cases presented as well as from
      the literature. Acute alterations of intraluminal pressure as well as a time
      interval of less than 6 h seems to increase the risk of re-bleeding during
      angiography. The introduction of and the growing experience with CT and MR
      angiography may in the near future provide sufficient diagnostic information for
      surgical planning and thus help to overcome the risk of aneurysmal re-rupture
      during intra-arterial angiography.

PMID- 12522596
TI  - Intradiploic meningoencephalocele.
AB  - We report on a 36-year-old patient who presented with coordinative problems in
      his right leg. The MRI study of his brain showed the extremely rare intradiploic
      meningoencephalocele which explained his symptoms. Most cephaloceles are inborn
      developmental disturbances and present with symptoms of different severity
      depending on the degree of associated malformations in early childhood. They
      usually demand immediate treatment. In the patient presented here the cephalocele
      belongs to the rare type of intradiploic meningoencephalocele. This is a variant
      of the intradiploic cerebrospinal fluid cyst and of traumatic instead of
      developmental origin.

PMID- 12522597
TI  - Reversible MRI changes of hypothalamus in a multiple sclerosis patient with
      homeostatic disturbances.
AB  - Multiple sclerosis (MS) patients occasionally present with homeostatic
      disturbances suggestive of hypothalamic dysfunction; however, the hypothalamus
      often appears normal on imaging, apart from confirmation in a few necropsy
      studies. In this article we describe a Chinese woman with atypical clinical
      presentation. She presented with relapsing symptoms and signs consistent with
      hypothalamic dysfunction including hyperprolactinema, syndrome of inappropriate
      secretion of anti-diuretic hormone (SIADH), hypersomnolence and temperature
      dysregulation. Serial MRI depicted the atypical reversible changes in the
      hypothalamus, correlating with the observed homeostatic abnormalities.

PMID- 12522598
TI  - Extreme fenestration of the right vertebral artery: magnetic resonance
      angiographic demonstration.
AB  - The authors describe an extreme fenestration of the right vertebral artery. This
      anomaly was found incidentally in a female patient undergoing MR imaging and MR
      angiography evaluation for severe dizziness and headache. Magnetic resonance
      angiography showed that the right posterior inferior cerebellar artery originated
      possibly extracranially and anastomosed with the terminal portion of the right
      vertebral artery, indicating the presence of an extremely large fenestration.
      This, to our knowledge, is the first report of MR angiographic demonstration of
      this variation.

PMID- 12522599
TI  - Leiomyosarcoma of sacrum: imaging and histopathologic findings.
AB  - A rare case of low-grade primary leiomyosarcoma of the sacrum is described in a
      young woman who suffered from pain in the right sacroiliac region. A lytic sacral
      mass was observed on conventional radiology and CT studies. Magnetic resonance
      imaging clearly showed Gd-DTPA enhancement in the entire mass demonstrating its
      hypervascularity, which was later confirmed by angiography. Histopathology and
      immunohistochemical results of biopsy and curettage of the lesion confirmed the
      diagnosis. We report on the features of a rare tumor entity through imaging and
      diagnostic methods.

PMID- 12522600
TI  - Migrating transient bone marrow edema syndrome of the knee: MRI findings in a new
      case.
AB  - We report a case of transient bone marrow edema syndrome migrating within two
      different compartments of the same knee. This unusual pattern of migration of the
      marrow edema, which has been previously described only in three cases of
      transient osteoporosis, may raise the suspicion of an aggressive disease.
      Radiologists should be aware of this phenomenon in order to avoid an aggressive
      management of this self-limiting disease.

PMID- 12522601
TI  - Chordoma of the low cervical spine presenting with Horner's syndrome.
AB  - Chordomas arising from the low cervical spine have been reported rarely. This
      case report expands the knowledge of chordomas of the low cervical spine by
      reporting the clinical, radiological, and pathological findings of a case of
      chordoma arising from C6 vertebra in a 61-year-old man presenting with left
      Horner's syndrome. This clinical presentation is uncommon for cervical chordomas
      and resulted from the tumor growth in the left carotid space resulting in the
      total encasement of common carotid artery and involvement of sympathetic fibers
      ipsilaterally.

PMID- 12522602
TI  - Ball-and-socket ankle joint with hypoplastic sustentaculum tali.
AB  - A case of unilateral ball-and-socket ankle joint associated with short limb and
      hypoplastic sustentaculum tali is reported. We think that hypoplastic
      sustentaculum tali was the cardinal feature in the anatomical and kinematic
      alterations of the foot in this patient. We review the embryonic development of
      hindfoot to ascertain the possible origin of this unusual finding.

PMID- 12522603
TI  - Hepatic involvement in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber
      disease).
AB  - Hepatic involvement in hereditary hemorrhagic telangiectasia is infrequent and
      poorly studied. We describe a 62-year-old woman with Rendu-Osler-Weber (ROW)
      disease and recurrent gastrointestinal bleeding episodes. Blood chemistry was
      consistent with the presence of cholestasis. Imaging studies revealed prominent
      vascular abnormalities in the liver and focal intrahepatic bile duct dilatations.
      The intimate anatomic relationship of the vascular abnormalities to the dilated
      bile ducts suggests that external vascular compression could have caused their
      dilatation. To our knowledge, this mechanism has not been proposed in the
      literature as a possible explanation of biliary dilatation in patients with ROW.

PMID- 12522604
TI  - Mature teratoma of the pancreas: CT and MR findings.
AB  - Mature teratoma of the pancreas is an unusual tumor. Like all teratomas it
      results from abnormal embryonal development of toti potent cells. Their contents
      may vary and may consist of ectodermal, endodermal, and mesodermal tissues. The
      radiologic appearance of these lesions depends on the proportions of various
      tissues of which they are composed. We report, to our knowledge, the first
      description of its CT and MR appearances.

PMID- 12522606
TI  - Intrahepatic splenosis: a case report.
AB  - Splenosis is heterotopic autotransplantation and seeding of splenic tissue. In
      the literature, only a few cases of splenosis involving the liver and the
      radiologic characteristics of these lesions have been reported. We report a case
      of intrahepatic splenosis diagnosed by ultrasound, computed tomography, magnetic
      resonance imaging and scintigraphic features. To our knowledge, our patient is
      the first case diagnosed only by radiologic and radionuclide examination without
      any intervention.

PMID- 12522605
TI  - Benign hepatic portal venous gas following caustic ingestion.
AB  - Hepatic portal vein gas has been documented in numerous conditions and is
      traditionally regarded as a poor prognostic sign. There are, however, several
      reports of portal vein gas with a benign course. We report the first case of
      transient hepatic portal vein gas secondary to the ingestion of a caustic
      substance. The literature of hepatic portal vein gas in benign disease is
      reviewed.

PMID- 12522607
TI  - Unusual imaging findings in Wilson's disease.
AB  - We present unusual imaging findings in the liver of a patient with Wilson's
      disease. On US, the liver contours were irregular and its echogenicity was
      increased with multiple, small hypo- and hyperechoic nodules. Prominent
      perihepatic fat layer was noted to be increased in thickness. On CT and MR,
      multiple, small, enhancing nodules were detected in the liver in the early
      arterial phase after administration of intravenous contrast material. Biopsy was
      consistent with chronic parenchymal liver pathology with dysplastic changes but
      without evidence of hepatocellular carcinoma. To our knowledge, dysplastic
      nodules enhancing at the arterial phase and thickened perihepatic fat layer have
      not been previously reported in patients with Wilson's disease.

PMID- 12522608
TI  - Detection of an occult hepatocellular carcinoma using ultrasound with liver
      specific microbubbles.
AB  - The radiological surveillance of cirrhosis to detect the development of
      hepatocellular carcinoma (HCC) is problematic because no highly sensitive and
      specific imaging investigation is available. Ultrasound is typically the first
      modality used but is less accurate than other imaging modalities. We report the
      first case of a patient with cirrhosis in whom US imaging with liver-specific
      microbubbles detected an HCC prior to its detection by MR. The use of liver
      specific microbubble US contrast agents is an exciting development in the
      detection of HCC in chronic liver disease and may help to rectify some of the
      shortcomings of US.

PMID- 12522609
TI  - Retained surgical sponge with migration into the duodenum and persistent duodenal
      fistula.
AB  - Migration of a retained surgical sponge into the bowel is a rare cause of bowel
      obstruction. Thus far, there have not been any reports that the site of initial
      migration of the sponge was identified by imaging studies or surgical exploration
      because the onset of symptoms is usually delayed. Unique about the case presented
      herein is that a barium meal follow-through study revealed a duodenal fistula
      that had developed after uneventful cholecystectomy due to a retained surgical
      sponge that had migrated into the duodenum and obstructed the distal jejunum.
      Imaging findings are presented and discussed.

PMID- 12522610
TI  - Jejunal diverticulitis with localized perforation diagnosed by ultrasound: a case
      report.
AB  - A rare case of a proximal jejunal diverticulitis is presented. The diagnosis was
      initially suggested by US and confirmed by CT. Ultrasound detected a hypoechoic
      irregular lesion continuous with the jejunum suggestive of the presence of
      diverticula. The presence of peridiverticular hyperechoic fat, associated with US
      signs of extraluminal air, evoked the diagnosis of a proximal jejunal
      diverticulitis, which was spontaneously walled-off. The diagnosis was confirmed
      by CT. The patient recovered after conservative treatment.

PMID- 12522611
TI  - Primary mesenteric tumor with phenotypical features of gastrointestinal stromal
      tumors.
AB  - We report a case of a primary mesenteric tumor that was discovered in a 71-year
      old man. Abdominal US accurately visualized the internal structure of the tumor
      but failed to determine the site of origin. Computed tomography suggested the
      mesenteric origin of the tumor before resection. The mass was removed and
      histopathological examination (including immunohistochemical and ultrastructural
      studies) was consistent with a primary gastrointestinal stromal tumor (GIST) of
      the mesentery, a very rare neoplasm scarcely reported in the radiology
      literature. Clinical, radiological, and pathological findings of this case are
      presented and the topic of primary mesenteric tumors with phenotypical features
      of GIST is reviewed.

PMID- 12522612
TI  - Inadvertent intrathecal use of ionic contrast agent.
AB  - Intrathecal administration of ionic contrast media may cause severe and fatal
      neurotoxic reactions due to their hyperosmolarity and ionic nature. They are
      therefore strictly contraindicated for all radiologic applications involving the
      central nervous system (e.g., myelography). We present a case in which
      ioxitalamate was accidentally injected intrathecally. The patient recovered
      completely due to a combination of the different therapeutic options reported in
      the literature, including early mechanical ventilation and neuromuscular
      paralysis, aggressive control of seizures, elevation of head and trunk to prevent
      cephalad migration of contrast, steroids, cerebrospinal fluid drainage and lavage
      and prophylactic antibiotics.

PMID- 12522613
TI  - Macular exanthema appearing 5 days after X-ray contrast medium administration.
AB  - We report a case of widespread, pruritic macular exanthema appearing 5 days after
      intravenous administration of the X-ray contrast medium, iohexol (Omnipaque) in a
      patient who had not previously received any X-ray contrast medium. The eruptions
      resolved in 7 days, leaving no residual lesions. When the patient was challenged
      intradermally with the same contrast medium 1.5 months after recovery, the same
      type of eruption developed 1 day after challenge. Histological examination of
      biopsies from positive skin test sites revealed the presence of a dermal
      infiltrate of lymphocytes. This case is another example of a late-onset adverse
      reaction to an X-ray contrast medium, mediated by specific T cells. The
      usefulness of intradermal skin testing for confirming the allergic nature of the
      reaction and for studying cross-reactivity pattern is emphasized.

PMID- 12522614
TI  - Behcet's disease involving the breast.
AB  - Behcet's disease is a vasculitis of unknown origin that was traditionally defined
      by oral and genital ulcers and uveitis. We describe a case of a patient with a
      diagnosis of Behcet's syndrome who presented a palpable lesion in the right
      breast with inflammatory signs. X-ray findings posed a differential diagnosis
      between tumoral and inflammatory pathology. The pathological findings confirmed a
      small-vessel vasculitis. We found two reports of breast involvement by this
      disease in the literature. Our patient was studied by mammogram and sonogram
      which together with clinical history are important to prevent delay in diagnosis
      and unnecessary therapeutic procedures.

PMID- 12522615
TI  - MR-guided laser-induced thermotherapy with a cooled power laser system: a case
      report of a patient with a recurrent carcinoid metastasis in the breast.
AB  - We report a case of a 52-year-old woman with a palpable recurrent metastasis of a
      neuroendocrine carcinoma to the upper outer quadrant of the right breast. For the
      treatment of this lesion, MR-guided laser-induced thermotherapy was performed
      with a cooled power laser system (Nd:YAG-Laser). An open 0.2-T MR unit was used
      for the monitoring of the laser energy delivery to the breast; thus, a
      thermosensitive fast low-angle shot 2D sequence for MR thermometry was used, so
      the ablation of the tumor and the increase of laser-induced necrosis could be
      interactively visualized with the repetitive use of this sequence. The
      postinterventional MR control exams 1 day and 4 months after laser-induced
      thermotherapy at the 1.5-T MR unit (Magnetom Symphony Quantum, Siemens, Erlangen,
      Germany) verified the complete ablation of the tumor without any signs of
      residual or relapsing tumor.

PMID- 12522616
TI  - Sarcoidosis of the breast.
AB  - We report a case of sarcoidosis of the breast in a 31-year-old woman who
      presented with a palpable breast mass. The mammography showed a spiculated mass
      without any microcalcifications. Ultrasonogram showed a hypoechoic mass. Computed
      tomography showed a spiculated nodule. T2-weighted MR images with fat-suppression
      technique showed a mass with irregular border that appeared to be an accumulation
      of small nodules. Gadolinium-enhanced dynamic study showed gradually increasing
      signal intensity. She underwent excisional biopsy and the pathological findings
      were consistent with that of sarcoidosis. The MRI findings were well correlated
      with histopathological appearance.

PMID- 12522617
TI  - Juvenile ossifying fibroma: CT and MR findings.
AB  - We describe the CT findings in four patients and the MR imaging in one patient
      with juvenile ossifying fibroma. Three lesions involved the maxillary sinus and
      extended to the surrounding structures; one lesion was confined to the maxillary
      bone. CT scan revealed well-defined, expansile lesions with variable amount of
      calcifications. On MRI one lesion had intermediate signal intensity with
      significant contrast enhancement.

PMID- 12522618
TI  - Serial MR imaging studies in enlarged endolymphatic duct and sac syndrome.
AB  - Large vestibular aqueduct syndrome (LVAS) is a congenital disorder characterized
      by progressive or fluctuating sensorineural hearing loss of unknown etiology.
      Serial MR examinations were performed before and after the development of hearing
      loss in two patients with LVAS. The signal and volume of the enlarged
      endolymphatic sac (EES) vary even in ears with stable hearing. In ears with
      fluctuating hearing, changes in EES signals were observed in only one of two
      patients. The finding that the EES volume and signal intensity vary dynamically
      independently of hearing is important for future research into the
      pathophysiology of hearing loss in this syndrome.

PMID- 12522619
TI  - Post-infectious diffuse venous stenosis after renal transplantation: duplex
      ultrasonography and CT angiography.
AB  - Venous stenosis is a rare vascular complication of renal transplantation. Venous
      stenosis usually occurs in early postoperative stage and manifests as a focal
      narrowing. We report a case of diffuse venous stenosis after 5 months following
      transplantation, which was suggested on duplex ultrasonography and directly
      visualized on CT angiography.

PMID- 12522620
TI  - Adrenal ganglioneuroblastoma in pregnant woman: diagnosis with three-dimensional
      ultrasound.
AB  - The diagnostic approach for evaluation of adrenal tumour in pregnant women is a
      problem. This article presents the multifactorial diagnosis of rare, incidentally
      detected massive adrenal tumour with 2D and 3D US. Grey-scale 2D and 3D US with
      tissue harmonic imaging showed inhomogeneous, encapsulated, solid tumour of the
      right adrenal region. Three-dimensional colour Doppler and power Doppler studies
      showed ample neovascularization in the tumour and the adrenal vein draining to
      the inferior vena cava similarly to angiographic studies performed in the past.

PMID- 12522622
TI  - Luteinized fat in Krukenberg tumor: MR findings.
AB  - To our knowledge, there is no description of the fat-containing Krukenberg tumor.
      We report on a case of Krukenberg tumor associated with luteinized fat, which
      showed hyperintensity on T1-weighted MR image. The diagnosis was surgically
      confirmed. Hyperintense portion of the Krukenberg tumor on T1-weighted image
      showed diminished signal intensity on fat-saturated, T1-weighted images.
      Krukenberg tumor should be considered in the differential diagnosis of ovarian
      masses when fat signal is seen.

PMID- 12522621
TI  - Pedunculated uterine leiomyoma associated with pseudo-Meigs' syndrome and
      elevated CA-125 level: CT features.
AB  - A 38-year-old woman presented with a 1-week history of low back pain, distension,
      weakness, and loss of appetite. Laboratory studies showed a serum CA-125 level of
      281 U/ml (normal value 1.2-32 U/ml). Abdominopelvic sonography revealed massive
      ascites, left pleural effusion, and a heterogeneous, hypoechogenic, and smoothly
      outlined solid mass. The mass had a close proximity and to the anterior side of
      the right ovary. Doppler sonography showed that the mass was hypervascularized.
      Computed tomography demonstrated numerous, tortuous vascular structures around
      the mass and along the omentum indicating its auxiliary vascularization from the
      omentum. Exploratory laparotomy and histopathological examination revealed
      pedunculated leiomyoma with parasitized blood supply from the omentum. Ascites
      and pleural effusion disappeared 6 months after surgery. We present the clinical
      and CT features of a parasitic leiomyoma adhering to the omentum.

PMID- 12522623
TI  - Posterior "Nutcracker" phenomenon in a patient with abdominal aortic aneurysm.
AB  - We report on a posterior "nutcracker" phenomenon due to an abdominal aortic
      aneurysm in a patient with a retro-aortic left renal vein. A 71-year-old man with
      a known abdominal aortic aneurysm presented in the emergency room with mild
      hematuria and flank pain. Computed tomography angiography revealed an aortic
      aneurysm, which compressed the left renal vein between the aorta and the
      vertebral column. Compression of the left renal vein, due to the aorta with
      consecutive congestion and hematuria as well as flank pain, was previously
      described as nutcracker phenomenon. In case of a retro-aortic left renal vein,
      increase of the aortic diameter can lead to compression of the renal vein and
      furthermore to the classical signs and symptoms of the "nutcracker" phenomenon,
      even though the aneurysm is not ruptured or there are no aorto-caval or aorto
      left renal vein fistulas.

PMID- 12522624
TI  - Double-blind ureteral duplication: report of two cases.
AB  - Blind ending of ureteral duplication is one of the most rare anomalies of the
      upper urinary tract. We report two cases of ureteral duplication with a blind
      ending both superiorly and inferiorly, and with no definite communication with
      the urinary tract.

PMID- 12522625
TI  - Complex bilateral polysyndactyly featuring a triplet of delta phalanges in a
      syndactylised digit.
AB  - The delta phalanx is a rare congenital skeletal anomaly. An abnormal C-shaped
      epiphysis is usually responsible for a progressive angular digital deformity
      observed either in hands or feet. Solitary delta phalanges are usually described.
      We report a case of bilateral congenital hand malformations featuring a triplet
      of delta phalanges affecting a single digit on one hand, together with a
      concealed central polydactyly on the other.

PMID- 12522626
TI  - Giant fibroma in the left ventricle of an infant: imaging findings in magnetic
      resonance imaging, echocardiography and angiography.
AB  - The diagnosis of a rare case of giant intraventricular fibroma in an infant by
      MRI in comparison with other imaging modalities, such as echocardiography and
      angiography, is discussed. For preoperative planning only MRI showed the
      myocardial infiltration. The myocardial blood supply of the tumor could be
      evaluated qualitatively by contrast-enhanced MRI, but the direct visualization of
      the distally located branches could only be assessed by coronary angiography.
      Magnetic resonance coronary angiography using the navigator technique failed to
      depict the distal part of the coronaries. The obstruction of the left ventricle
      outflow tract could be assessed and quantified by all imaging modalities.

PMID- 12522627
TI  - Fatty degeneration in a Wilms' tumour after chemotherapy.
AB  - We report a case of extensive fatty change in a Wilms' tumour after chemotherapy
      demonstrated on CT associated with an increase in tumour volume, in a 10-month
      old girl with Beckwith-Wiedemann syndrome. Changes in tumour characteristics
      after chemotherapy on imaging usually reflect necrosis, haemorrhage and
      calcification. Assessment of response to therapy is dependent on a documented
      reduction in tumour volume. In this case, CT showed an increase in tumour size
      with development of an extensive fatty component following treatment. Subsequent
      histological examination on the nephrectomy specimen confirmed an extensive fatty
      component with no evidence of residual blastema. The development of such an
      extensive fatty component is very unusual. In this case such fatty change was an
      indicator of tumour sensitivity and response to treatment.

PMID- 12522628
TI  - Acute appendicitis in a premature baby.
AB  - A case of acute appendicitis in a premature baby in whom diagnosis was suggested
      on plain films of the abdomen is presented. In this baby air in a hollow viscus
      suspected of being an enlarged appendix was the clue to diagnosis. The diagnostic
      dilemma of this rare and life-threatening condition in premature babies and
      newborns is underlined. The relevance of different imaging modalities and of
      different findings in this age group is discussed. Awareness of this rare
      condition and possible differential diagnosis in newborns and premature babies is
      stressed.

PMID- 12522629
TI  - Chronic pneumonitis of infancy.
AB  - Chronic pneumonitis of infancy (CPI) is a very rare lung disease in infants and
      young children. We report a 33-day-old infant with CPI, focusing on the
      radiologic aspects of the disease. Chest radiographs showed variable and non
      specific appearances including ground-glass shadowing, consolidation, volume
      loss, and hyperinflation. Dense alveolar opacities progressed as CPI advanced.
      The radiologic features of our case reflected pathologic changes.

PMID- 12522630
TI  - Diagnosis of a cardiac angiosarcoma by fluorine-18 fluordeoxyglucose positron
      emission tomography.
AB  - Cardiac angiosarcoma is a rare tumour entity with a poor prognosis. Early
      detection is difficult but important for the further course of the disease. We
      report on a young patient with a tumour of unknown origin and dignity of the
      right atrium. Magnetic resonance imaging, CT and echocardiography were sufficient
      in localisation, but no statement on the dignity was possible. Furthermore,
      staging led to ambiguous results. Malignancy could be proved by fluorine-18
      fluordeoxyglucose positron emission tomography, leading to early surgery.
      Histology revealed a poorly differentiated angiosarcoma.

PMID- 12522631
TI  - Thoracic lymphangiectasis presenting with chyloptysis and bronchial cast
      expectoration.
AB  - A 70-year-old man with recurrent undiagnosed episodes of bronchial cast
      expectoration and pulmonary infiltrates on chest radiography for 15 years is
      described. The diagnosis of chyloptysis was established by chemical analysis of
      the bronchial aspiration. We emphasize the radiological findings of this rare
      observation. The CT-associated lymphangiography showed mediastinal
      lymphangiectasis with retrograde opacification of mediastinal and hilar lymph
      nodes as well as submucosal lymphatic vessels protruding into the lumen of the
      tracheo-bronchial tree without evidence of thoracic duct obstruction as well as a
      "crazy-paving appearance." Congenital incompetence of the valves of the lymphatic
      vessels originating from the thoracic duct is held to be the cause. Chyloptysis
      and pulmonary lymphatic disorder should be sought in cases of bronchial cast
      expectoration.

PMID- 12522632
TI  - Radiofrequency thermal ablation of a metastatic lung nodule.
AB  - Pulmonary metastases are a common finding in patients with colonic
      adenocarcinoma. We report the treatment of a metastatic lung nodule with
      radiofrequency (RF) ablation under CT guidance. This case illustrates the use of
      RF ablation in a patient in whom surgical resection was no longer possible and
      where chemotherapy was unlikely to produce benefit. This technique may offer a
      viable method of cytoreduction when other treatments have not succeeded.

PMID- 12522633
TI  - Exogenous lipoid pneumonia with unusual CT pattern and FDG positron emission
      tomography scan findings.
AB  - We report a case of an exogenous lipoid pneumonia that appeared as a spiculated
      calcified mass on CT scan in which a positron emission tomography (PET) scan was
      performed before histological analysis. The F-18 fluoro-deoxy-D-glucose (FDG) PET
      showed a pattern highly suggestive of malignancy which, to our knowledge, has not
      yet been described. Similar to inflammatory and infectious lung diseases, lipoid
      pneumonia may be a false-positive case of F-18 FDG uptake.

PMID- 12522634
TI  - MR imaging of myocardial haematoma after blunt chest injury.
AB  - Myocardial contusion after a chest trauma is a frequently under-diagnosed injury.
      We report two cases of myocardial contusion in which MR imaging, thanks to its
      contrast capability, was able to assess the presence of a haematoma and in one
      case to demonstrate the recovery of the lesion.

PMID- 12522635
TI  - Detection of malignant right coronary artery anomaly by multi-slice CT coronary
      angiography.
AB  - Coronary artery anomalies occur in 0.3-0.8% of the population and infer a high
      risk for sudden cardiac death in young adults. Diagnosis is usually established
      during coronary angiography, which is hampered by poor spatial visualization.
      Magnetic resonance imaging is an alternative, but it is not feasible in the
      presence of metal objects or claustrophobia. In this report, a 15-year-old boy
      experienced ventricular fibrillation and was successfully resuscitated. Cardiac
      catheterization was inconclusive, and pacemaker implantation prohibited the use
      of MR imaging. Multi-slice CT coronary angiography revealed a malignant anomalous
      right coronary artery.

PMID- 12522636
TI  - Long-term success of endovascular treatment of benign superior vena cava
      occlusion with chylothorax and chylopericardium.
AB  - The most likely etiology of benign obstruction of the superior vena cava (SVC)
      include fibrosing mediastinitis and iatrogenic etiologies such as sclerosis and
      obstruction caused by pacemakers and central venous catheter. Percutaneous
      stenting of SVC has been used with success both in malignant and benign superior
      vena cava syndrome; however, long-term follow-up of endovascular procedures is
      not well known. We present a case of a patient with complete occlusion of SVC of
      benign etiology, presenting dramatically with bilateral chylothorax and
      chylopericardium with cardiac tamponade, who underwent successful vena caval
      revascularization with thrombolytic therapy and placement of self-expanding
      metallic stent. The 42-month follow-up could encourage endovascular procedures
      even in SVC syndrome of benign etiology.

PMID- 12522637
TI  - Balloon-assisted ultrasound-guided direct percutaneous embolization of a
      peripheral pseudoaneurysm with n-butyl cyanoacrylate.
AB  - We report the ultrasound-guided direct percutaneous injection of n-butyl
      cyanoacrylate to embolize an iatrogenic peripheral pseudoaneurysm secondary in a
      33-year-old patient undergoing hemodialysis. We protected the parent artery with
      inflation of an angioplasty balloon across the neck during the cyanoacrylate
      injection. Complete occlusion of the pseudoaneurysm was achieved without ischemic
      complication.

PMID- 12522639
TI  - The role of gadolinium-enhanced MR imaging in the preoperative evaluation of
      inflammatory abdominal aortic aneurysm.
AB  - Inflammatory abdominal aortic aneurysm is an uncommon variant of abdominal aortic
      aneurysms. Thorough preoperative imaging of the extent of the aneurysm and
      inflammation and the associated complications are crucial in the management of
      this condition. We report a case of inflammatory abdominal aortic aneurysm where,
      after the initial contrast-enhanced CT, gadolinium-enhanced MR imaging was used
      to define the true extent of the inflammation and differentiate inflammation from
      mural thrombus at the iliac extension of the aneurysm. The imaging appearances
      are presented and the impact of MR imaging on further surgical management options
      including endovascular repair are discussed.

PMID- 12522638
TI  - Coil compaction after embolization of the superior mesenteric artery
      pseudoaneurysm.
AB  - A 58-year-old man with an abscess of the psoas muscle was returned to our
      hospital with hematemesis. Two years earlier, he had undergone coil embolization
      for a superior mesenteric artery (SMA) pseudoaneurysm secondary to pancreatitis.
      Based on the physical examination, serum amylase level, and abdominal
      radiographs, a diagnosis of acute exacerbation of pancreatitis and coil
      compaction of the SMA pseudoaneurysm was made. The patient underwent re
      embolization for the coil compaction using interlocking detachable coils. His
      condition improved gradually, and he was discharged 3 weeks later. To our
      knowledge, this is the first report of coil compaction of SMA pseudoaneurysm.

PMID- 12522640
TI  - Secondary aortoenteric fistula: active bleeding detected with multi-detector-row
      CT.
AB  - We report a case of active bleeding of a secondary aortoenteric fistula (SAEF),
      in which CT angiography with multi-detector-row CT (MDCT) was finally diagnostic
      after negative catheter angiography and unsatisfactory endoscopy. The MDCT
      angiography clearly demonstrated the fistulous tract between the abdominal aortic
      graft and the duodenum. The dynamic process of bleeding was confirmed as a net
      increase of contrast agent accumulation in the duodenum through different phases.
      The MDCT angiography with its excellent 3D image quality is therefore a valuable
      method in the assessment of active SAEF bleeding.

PMID- 12522641
TI  - MR angiography of the lower extremities with a moving-bed infusion-tracking
      technique.
AB  - PURPOSE: To assess the value of MR angiography (MRA) with automatic table
      movement in a consecutive series of patients with peripheral arterial disease.
      METHODS: Seventy-two patients underwent both conventional angiography (CA) and
      MRA for peripheral arterial occlusive disease. Both techniques were scored in a
      masked way. Consensus scoring for CA was compared with MRA scoring per observer.
      If there was a discrepancy in scoring of a segment on MRA and CA, the images were
      reviewed and a consensus arrived at. RESULTS: Observer A found 7.4% and observer
      B found 6.5% of the segments could not be analyzed on MRA. Observer A scored
      11.4% dissimilar on MRA and CA, observer B 15.2%. In the aortoiliac arteries,
      this was mainly caused by stents and overestimation of stenoses; in the crural
      arteries it resulted from underestimation of the stenoses on MRA. Overall
      sensitivity and specificity for the aortoiliac, femoropopliteal and crural
      vessels were respectively 90% and 91%, 90% and 96%, 59% and 96% for observer A,
      and 85% and 91%, 84% and 89%, 68% and 85% for observer B. CONCLUSION: Although
      MRA of the lower extremities is a promising technique, improvements still need to
      be made. In particular, MRA below the knee is suboptimal for clinical use.

PMID- 12522642
TI  - Percutaneous removal of retained calculi from the abdomen.
AB  - With rising pressure placed on health service resources minimally invasive
      techniques requiring only short hospital admissions are increasing in importance.
      We describe the techniques used to remove calculi from the peritoneal cavity
      which had been retained after surgery and continued to cause clinical problems.
      In both cases described the calculi lay within abscess cavities associated with
      fistulous tracks to the skin. The fistulae were dilated to allow passage of
      therapeutic radiologic and endoscopic equipment enabling manipulation and
      subsequent extraction of the stones. In both cases removal of the calculi allowed
      complete resolution of the fistulae and the patients made a full clinical
      recovery. Removal of gallstones which have escaped into the peritoneum at
      laparoscopic cholecystectomy leading to sepsis has been described; we describe
      the novel management of a patient in whom extraction had already been attempted,
      at another hospital, without success. Removal of an appendicolith, described here
      in another patient, does not appear to have been reported previously.

PMID- 12522643
TI  - Shortening and migration of Wallstents after stenting of central venous stenoses
      in hemodialysis patients.
AB  - PURPOSE: To report our results for the placement of central venous stents in
      patients undergoing hemodialysis. METHODS: Ten Wallstents (Schneider, Bulach,
      Switzerland) were placed in 10 patients with shunt thrombosis, shunt dysfunction
      or arm swelling associated with central vein stenosis or occlusion. Technical
      success, patency and complications were evaluated. RESULTS: Stent deployment was
      successful in all cases. In seven cases (70%) there was significant delayed stent
      shortening. In two of these cases there was also stent migration. All these cases
      required additional stents. Primary patency rates at 6, 12 and 24 months were
      66%, 25% and 0. Twenty-three additional procedures (percutaneous transluminal
      angioplasty or stenting) were required to achieve secondary patency rates at 6,
      12 and 24 months of 100%, 75% and 57%. CONCLUSION: Stent placement in the central
      veins of dialysis patients has a high technical success rate resulting in
      symptomatic relief and preservation of access. Repeat interventions are required
      to maintain patency. Significant delayed shortening of the Wallstent occurred in
      70% of patients which may have affected the patency rates. Strategies are
      suggested to avoid this problem.

PMID- 12522644
TI  - Internal iliac artery aneurysm embolization with fibrin sealant: a simple and
      effective solution.
AB  - Endovascular treatment of internal iliac artery (IIA) aneurysms is an attractive
      alternative to surgical management, because the former is associated with less
      morbidity and mortality. Embolization with coils or exclusion of the IIA orifice
      with stent-grafts are the preferred techniques. Although uncommon, technical
      failures occur with reported aneurysm rupture. Two patients with IIA aneurysms
      are reported here, where we describe successful occlusion of their IIA aneurysms
      with the use of fibrin sealant, after initial failure of coil embolization.

PMID- 12522645
TI  - Arterial embolization of giant hepatic hemangiomas.
AB  - Hepatic cavernous hemangiomas are usually small and asymptomatic. They are
      usually discovered incidentally and only a few require treatment. However, giant
      hemangiomas may cause symptoms, which are indications for treatment. We describe
      four cases of symptomatic giant hepatic hemangiomas successfully treated with
      transcatheter arterial embolization, performed with polyvinyl alcohol particles.
      There were no complications. Follow-up with clinical and imaging examinations
      showed disappearance of symptoms and decrease in size of lesions.

PMID- 12522648
TI  - Slowly developing perigraft seroma after a modified Blalock-Taussig shunt.
AB  - We report a 26-year-old patient with slowly developing perigraft seroma 15 years
      after a modified Blalock-Taussig shunt with an expanded polytetrafluorethylene
      graft. The mediastinal mass was first observed on a chest x-ray film 8 years
      after the shunt operation. The mass contained massive gelatinous or organic
      tissues with a severely calcified pseudocapsule, and it was adjacent to the
      calcified but functioning graft. No fluid collections were noted. The
      histological findings were compatible with a seroma. No recurrence was noted on
      last follow-up 1 year postoperatively.

PMID- 12522650
TI  - Adrenomedullin and nitrite levels in children with dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is an important cause of chronic congestive cardiac
      failure in children. In patients with idiopathic DCM, endothelium vasomotor
      function is disturbed. There are many studies on the roles of nitric oxide (NO)
      and adrenomedullin (AM) in adult patients with DCM. However, to our knowledge, no
      studies have investigated the level of AM and NO in children with idiopathic DCM.
      We determined plasma and urinary AM and total nitrite concentrations in children
      with idiopathic DCM and investigated the correlation between these and other
      clinical and laboratory findings. Eleven patients with DCM, ranging in age from 5
      month to 14 years, were compared to 10 healthy age- and sex-matched controls.
      Plasma (pmol/ml) and urinary (pmol/mg creatinine) AM levels were significantly
      lower than in the healthy controls (19.55 +/- 2.36 vs 51.61 +/- 7.22 and 28.29 +/
      20.66 vs 68.87 +/- 40.23, respectively; p <0.001). Plasma and urinary AM levels
      were negatively correlated with ejection fraction (EF) and fractional shortening
      (FS). The plasma (Mmol/L) and urinary nitrite levels (Mmol/mg creatinine) were
      not different between patients and controls [50.90 +/- 17.50 VS 53.40 +/- 26.05
      (P > 0.05) and 1.98 +/- 1.24 vs 2.75 +/- 1.68 (p > 0.05), respectively]. In our
      study, the first to analyze AM and nitrite levels in children with DCM, plasma
      and urinary AM levels were found to be decreased. A possible explanation for this
      reduction could be depletion of the viable myocyte population. However, this
      hypothesis must be clarified by further studies.

PMID- 12522651
TI  - Prevalence of congenital heart diseases in oral cleft patients.
AB  - To establish the prevalence of congenital heart diseases (CHDs) in cleft
      patients, the type of cleft and the presence of a syndrome were coded in 220
      patients. A Doppler echocardiogram with color-flow mapping (DE) was obtained in
      all patients. Mean age was 112.0 +/- 101.2 months (range, 1-576 months), and
      56.8% (125) were males. Cleft lip and palate occurred in 144 patients (65.5%),
      cleft lip in 40 (18.2%), and cleft palate in 36 (16.4%). Cleft palates were more
      frequent among females. Twenty-four CHDs were diagnosed in 21 of 220 patients
      (9.5%): 7 mitral valve prolapses, 6 atrial septal defects, 4 patent ductus
      arteriosus, 3 ventricular septal defects, 2 cases of tetralogy of Fallot, 1
      pulmonary stenosis, and 1 bicuspid aortic valve. The presence of CHD did not
      correlate with the type of cleft. Syndromes occurred in 28 patients (12.7%), and
      this association was higher among patients with a cleft palate.

PMID- 12522652
TI  - Dobutamine stress echocardiography in the evaluation of young patients with
      Kawasaki disease.
AB  - There has been no consistent approach to the follow-up of Kawasaki disease
      patients for remote coronary perfusion abnormalities. Dobutamine stress
      echocardiography (DSE) has become a standard method for evaluation of perfusion
      abnormalities in adults with coronary artery disease. In addition, DSE has been
      used with success in some pediatric patients. The purposes of this study were to
      evaluate safety and accuracy of DSE in the follow-up of patients with Kawasaki
      disease, to evaluate whether DSE adds any additional value to the resting
      echocardiogram, and to determine the association of DSE results with American
      Heart Association (AHA) risk level categories. DSE was performed 1 month to 13
      years after acute Kawasaki disease in 47 patients (range, 3.8-22.6 years; 33
      males and 16 females). Patients were stratified according to AHA risk level
      categories (I-V). Ischemia was defined as a new or worsening regional wall motion
      abnormality or >1 mm ST segment depression on the electrocardiogram during DSE.
      In 45/47 patients, DSE was completed successfully (i.e., achievement of target
      heart rate or development of ischemia). No patients in risk levels lower than V
      (i.e., patients without coronary artery stenoses) had positive DSE, whereas 2/4
      (50%) in the risk level V category had positive DSE, both of whom had coronary
      occlusion >50% confirmed by angiography. Of the 2 AHA risk level V patients with
      negative DSE, 1 had extensive collateralization and the other had coronary
      obstruction <50%. DSE is a safe and feasible method for the evaluation of
      children with Kawasaki disease. DSE provides a confirmatory benefit and may be a
      useful screening alternative to cardiac catheterization during follow-up.
      Patients in AHA risk levels I-IV are unlikely to have dobutamine-induced coronary
      perfusion abnormalities. Patients in the risk level V category may or may not
      have positive DSE depending on the degree of both coronary obstruction and
      collateralization.

PMID- 12522653
TI  - Congenital aortic regurgitation due to absent aortic cusps and high-degree mitral
      stenosis.
AB  - Congenital absence of aortic cusps leads to severe aortic regurgitation. We
      present a newborn with this rare entity with extreme mitral stenosis. Hemodynamic
      features were those of hypoplastic left heart syndrome. Surgical management
      consisted of initial modified Norwood procedure followed by orthotopic heart
      transplantation.

PMID- 12522654
TI  - Treatment of coexistent coarctation and aneurysm of the aorta with covered stent
      in a pediatric patient.
AB  - Intravascular stents have emerged as an effective alternative to surgery and
      balloon angioplasty in the treatment of native and recoarctation of aorta.
      Balloon angioplasty, although effective in the treatment of native coarctation of
      the aorta, is associated with several complications such as recoarctation,
      aneurysm formation, aortic dissection, and vascular injury. In this report, we
      present the use of a covered stent to treat a patient who developed recoarctation
      of the aorta with an associated aneurysm following balloon angioplasty of her
      native coarctation.

PMID- 12522655
TI  - The midwall stress-velocity relationship during manipulation of afterload.
AB  - Despite providing a physiological correction, measurements of contractility using
      the midwall stress-velocity relationship still show evidence of an unexplained
      hypercontractile state in some children. We investigated if by using midwall
      shortening indexes, the known overestimation of contractility at low afterload
      could be prevented. In 12 piglets (5 or 6 weeks old), afterload was manipulated
      by balloon occlusion of the descending aorta and infusion of sodium nitroprusside
      up to 5 mg/kg/min, and left ventricular function was measured using multiple
      variables. The regression line between the echocardiographically derived midwall
      velocity of circumferential fiber shortening and end systolic wall stress
      differed from the regression line of the endocardial stress-velocity
      relationship. Although the midwall regression line was almost horizontal (or
      afterload independent) for end systolic wall stress values of more than 30 g/cm2,
      the slope was still steeper below a certain point of afterload. The increased
      midwall velocity of fiber shortening at low afterload is comparable to the
      endocardial stress-velocity relationship and could account for the pseudo
      hypercontractile state found in some children.

PMID- 12522656
TI  - Cardiac dysrhythmias in pediatric patients before and 1 year after transcatheter
      closure of atrial septal defects using the amplatzer septal occluder.
AB  - To prospectively assess the incidence of cardiac dysrhythmias before and after
      closure of atrial septal defects (ASDs) using the Amplatzer septal occluder
      (ASO), 24-hour Holter electrocardiograms (ECGs) were performed before and 1 year
      after the procedure in 23 pediatric patients (9 male and 14 female). Patients'
      ages ranged from 2 to 15 years (mean, 7.1 years). All had an ASD of the secundum
      type that was completely closed (n = 22) or had a small residual shunt (n = 1).
      No preexisting dysrhythmia was present in 22 patients; atrioventricular nodal
      reentrant tachycardia had been diagnosed in 1 patient. During the observation
      period, no clinical dysrhythmia occurred. Analysis of the Holter ECGs before the
      intervention showed regular sinus rhythm in 20 patients and sinus rhythm with
      intermittent atrial rhythm in 3 patients. Atrial premature complexes (APCs) were
      detected in 1 patient, and a ventricular couplet was present in 1 patient. The
      Holter ECG 1 year after the intervention showed sinus rhythm in 18 patients and
      sinus rhythm with intermittent atrial rhythm in 5 patients. APCs were still
      observed in 1 patient and seen for the first time in 1 patient; 1 patient and
      rare ventricular premature complexes. In conclusion, cardiac dysrhythmias on
      Holter ECG in pediatric patients before and 1 year after transcatheter ASD
      closure with the ASO device are rare and benign. Regular Holter monitoring seems
      to be useful in detecting late dysrhythmias.

PMID- 12522658
TI  - Streamlining fluid pathways lessens flow energy dissipation: relevance to
      atriocavopulmonary connections.
AB  - Flow energy dissipation reduces cardiac efficiency, particularly in the Fontan
      modified, single-ventricle heart. To provide insight into flow energetics
      relevant to Fontan-type anatomy, a simple, analytical description of fluid motion
      was employed. Mechanical energy balance and the force-momentum relationship were
      used to describe theoretical pressure changes and flow energy losses. When either
      flow's cross-sectional area or direction changes abruptly, fluid disturbances
      ensue that can lead to erosion of a stream's available energy. Conversely,
      passages anatomically streamlined to favor gradual alterations in these flow
      characteristics lessen such fluid dynamic effects. We show by analogy that flow
      energy dissipation becomes clinically important in Fontan circuits when the
      magnitude and/or direction of the average velocity of flow suddenly changes as
      fluid enters or leaves a large chamber or negotiates a sharp bend in its
      connection pathway.

PMID- 12522657
TI  - Sinus node dysfunction after intraatrial lateral tunnel and extracardiac conduit
      fontan procedures.
AB  - This study compares the effects of two techniques for the Fontan procedure
      intraatrial lateral tunnel (IALT) and extracardiac conduit (ECC) -on sinus node
      dysfunction. Between January 1992 and December 1998, 54 patients underwent a
      total cavopulmonary connection Fontan procedure. Of these, 36 had follow-up 24
      hour Holter recordings, and they constitute the population for this study. The 24
      hour Holter recordings were performed between January 1998 and March 1999 and
      were evaluated for sinus node dysfunction and atrial tachycardia. Clinical follow
      up (18 +/- 11 months for the IALT group vs 34 +/- 19 months for the ECC group; p
      = 0.002) and surface electrocardiograms were also reviewed. Among the 36
      patients, 19 had an IALT and 17 had an ECC Fontan procedure. The incidence of
      sinus node dysfunction was 4/19 (21%) in the IALT group and 10/17 (59%) in the
      ECC group (p = 0.04). No patient from either group had an identified episode of
      atrial tachycardia. No permanent pacemaker was placed in the IALT group, whereas
      three were placed in the ECC group, all for sinus node dysfunction. In summary,
      patients with both IALT and ECC had an important incidence of sinus node
      dysfunction. The incidence of sinus node dysfunction was higher in the ECC group,
      which may have been due to longer follow-up in this group. Atrial tachycardia was
      not observed in either group. Although the IALT group had less sinus node
      dysfunction than the ECC group and appeared to require less permanent pacing,
      these data may be too limited to serve as the criteria for choosing between these
      two techniques for performing the Fontan procedure.

PMID- 12522659
TI  - Thrombosis in children with cardiac pathology: frequency of factor V Leiden and
      prothrombin G20210A mutations.
AB  - This study analyzed 28 thrombotic children with various cardiac disorders. They
      comprise 17% of a total of 168 patients with thrombosis from a single center.
      Among the 28 patients, 21 had congenital heart disease and 7 were diagnosed with
      cardiomyopathy. The patients with thrombosis were evaluated for congenital and
      acquired thrombotic risk factors. In addition to cardiac disorders, two, three,
      or more risk factors were present in 61% of the children with thrombosis. Two
      common mutations, namely factor V Leiden and prothrombin G20210A mutations, were
      found in 6 patients (22%). Nine patients (32%) died of infection, congenital
      heart disease, cardiomyopathy, thrombosis, operation, or a combination of these;
      two patients required surgical intervention. Following cardiac angiography, due
      to necrosis, amputation of the right index finger and right lower extremity was
      performed on 1 patient. The second patient's index fingers had to be amputated
      and resection of the bowel was performed following the operation on coarctation
      of the aorta. This study indicates that congenital heart disease and
      cardiomyopathy are two common cardiac disorders that may lead to the development
      of thrombosis. The majority of thrombosis develops within the heart and/or its
      great vessels. The second predominant site for thromboembolic symptoms is in the
      brain, including sinovenous thrombosis.

PMID- 12522660
TI  - Bone marker alterations in patients with type 1 Gaucher disease.
AB  - Bone involvement is one of the most disabling aspects of type I Gaucher disease
      and its pathophysiology is still not well understood. As an invasive procedure,
      bone biopsies are not appropriate in a large population study. The development of
      sensitive bone resorption and formation tests have allowed the authors to study
      bone metabolism in a noninvasive manner in a group of type 1 Gaucher patients.
      Ten type I Gaucher adult patients with mild-to-severe bone disease were
      evaluated. Bone mineral density and markers of bone formation (total alkaline
      phosphatase and isoenzymes, carboxyterminal propeptide of type I procollagen,
      osteocalcin) and resorption (carboxyterminal telopeptide of type I collagen,
      urinary hydroxyproline, free-deoxypyridinoline and calcium) were measured in
      patients and in a control group, matched for sex and age. In Gaucher patients,
      carboxyterminal propeptide of type I procollagen (PICP), a bone formation index,
      was significantly lower compared with normal subjects (mean 101.17 ng/ml vs
      140.75 ng/ml, P = 0.038), and analysis of bone resorption indexes showed a
      significant increase (mean 4.24 ng/ml vs 2.87 ng/ml, P = 0.012) of serum
      carboxyterminal telopeptide of type I collagen (ICTP). No significant differences
      were observed in osteocalcin, alkaline phosphatase, and urinary hydroxyproline.
      Bone mineral density revealed osteopenia in six patients, with a mean Z-score of
      ?1.04. It was not possible to show a relationship between sex, splenectomy
      status, age, weight, spleen, and liver volume and bone density, expressed as a Z
      score nor a correlation between Z score and severity of skeletal disease. Results
      have shown a predominance of the resorption phase in the bone metabolism of
      Gaucher patients. These markers could be useful in monitoring the effect of
      enzyme replacement therapy on Gaucher disease skeletal involvement.

PMID- 12522661
TI  - Alendronate and etidronate do not regulate interleukin 6 and 11 synthesis in
      normal human osteoblasts in culture.
AB  - Bisphosphonates exert a potent inhibitory effect on bone resorption. Several
      studies have been performed, with contradictory results, to ascertain whether the
      effect of bisphosphonates on osteoclasts could be produced, at least in part, by
      modulation of the synthesis of resorption-promoting factors by osteoblasts. The
      aim of this study was to evaluate the effect of etidronate (10-4-10-9 M) and
      alendronate (10-7-10-12 M) on the production of IL-6 and IL-11 using human
      osteoblast cultures. Cytokines were quantified by ELISA, and mRNA expression was
      tested. Treatment with alendronate and etidronate had no effect on the synthesis
      of IL-6 or IL-11, and IL-6 and IL-11 mRNA levels. These results were obtained
      both in nonstimulated cultures and in cultures stimulated by means of TNF-a, IL
      1b, and TNF-a+IL-1b, with or without FCS. In conclusion, a possible indirect
      osteoclast-mediated effect of alendronate and etidronate on bone resorption would
      not be exerted through reduction in osteoblastic synthesis of IL-6 and IL-11.

PMID- 12522662
TI  - Interstitial collagenase activity stimulates the formation of actin rings and
      ruffled membranes in mouse marrow osteoclasts.
AB  - Interstitial collagenase activity stimulates bone resorption by mouse marrow
      osteoclasts [1]. Here, we show that collagenase activity promotes bone resorption
      by activating adherent osteoclasts to resorb bone. Inhibition of interstitial
      collagenase activity, either with peptidomimetic hydroxymates or with a specific
      anti-interstitial collagenase inhibiting antibody, reduced bone resorption by 73
      92%. Equal numbers of osteoclasts adhered to bone in the presence of collagenase
      inhibitors and osteoclast survival was unaffected. In contrast, formation of
      actin rings and polarization of the vacuolar-H+-ATPase (V-ATPase) to ruffled
      membranes, two indicators of osteoclast activation, were decreased by inhibiting
      collagenase activity and stimulated in the presence of cleaved or heat-denatured
      type I collagen in proportion to increases and decreases of bone resorptive
      activity. Addition of excess recombinant osteoprotegerin-ligand to cultures did
      not restore bone resorption in the presence of interstitial collagenase
      inhibitors. These data support the hypothesis that cleaved collagen stimulates
      osteoclastic bone resorption by triggering cytoskeletal reorganization and
      transport of V-ATPase from cytoplasmic stores to ruffled membranes.

PMID- 12522663
TI  - Aquaporin expression in developing human teeth and selected orofacial tissues.
AB  - The aquaporin (AQP) family of membrane channel proteins function as selective
      pores through which water, glycerol, and other small solutes cross the cell
      plasma membrane. To date, 11 members of this transporter family, designated AQP0
      10, have been cloned and characterized in humans. The AQPs are differentially
      expressed in temporospatial patterns, where different AQPs demonstrate distinct
      tissue distributions that may reflect differing cell membrane transport
      functions. The purpose of this study was to evaluate AQP expression in the
      developing human teeth by RT-PCR and Western blot analysis. To access the
      generality of AQP expression, selected other orofacial tissues were studied by RT
      PCR. The presence of all eleven human AQPs was screened in each tissue by RT-PCR.
      Positive amplification products were verified by direct DNA sequencing. AQPs 1,
      3, 4, 5, 6, and 10 were identified by RT-PCR in developing teeth, and AQP1, 3, 5,
      and 6 were confirmed by Western blot analysis. AQP 4 was not detected by Western
      blot analysis, and we were unable to test for the recently identified AQP10 due
      to unavailability of antibodies. AQPs detected in other orofacial tissues by RT
      PCR included gingiva (AQP3, 7, 10); Meckel's cartilage (AQP1, 3, 4, 5, 6);
      submandibular gland (AQP1, 3, 4, 5, 6, 7); masseter muscle (AQP1, 3, 4, 7, 8,
      9,10); and infrahyoid muscle (AQP1, 3, 4,10). These results demonstrate that
      multiple aquaporins are expressed in developing teeth and in selected orofacial
      tissues.

PMID- 12522664
TI  - A case for estrogen receptors on cell membranes and nongenomic actions of
      estrogen.

PMID- 12522665
TI  - Two inbred rat strains that differ substantially in hip fragility.
AB  - One approach to identifying the genetic influences on skeletal phenotypes
      involves the creation and genetic mapping of a population of the second filial
      (F2) offspring derived from a cross of two inbred strains of rodents. The two
      inbred strains should be chosen based upon a large difference in the phenotype of
      interest, e.g., bone fragility. We found previously that considerable variation
      exists in fragility phenotypes among inbred strains of rats, and the phenotypic
      variation was site specific. In particular, two inbred rat strains, Copenhagen
      2331 (COP) and Dark Agouti (DA), were found to differ significantly in femoral
      neck geometry and strength. The aim of this study was to further characterize hip
      fragility in COP and DA rats at 6 months of age using peripheral quantitative
      computed tomography (pQCT), microcomputed tomography (mCT), and biomechanical
      tests. COP rats had a significantly wider femoral head (P = 0.04) and neck (P =
      0.007), significantly larger bone area and cortical bone area in femoral neck (P
      = 0.03 and P = 0.02, respectively), significantly greater total bone mineral
      content (BMC) and cortical BMC in femoral neck (P = 0.01 and P = 0.001,
      respectively), and 65% greater femoral neck cross-sectional moment of inertia (P
      = 0.02), as compared with DA rats. As a result, COP rats had 22% higher ultimate
      force (Fu), 68% higher ultimate displacement (du), and 81% higher work to failure
      (U) than DA rats in the femoral neck biomechanical test (P = 0.04, P = 0.01, and
      P = 0.02, respectively). The biomechanical properties for the femoral midshaft
      and lumbar vertebrae were virtually the same in the two rat strains, suggesting a
      hip-specific genetic effect on bone strength. These data indicate that
      significant phenotypic variation at the femoral neck site exists between these
      two inbred strains, and COP rats appear to have genes that specifically enhance
      the femoral neck structural properties and strength. Therefore these two inbred
      strains, COP with DA, may facilitate effective genetic studies of hip fragility.

PMID- 12522666
TI  - Estrogens and estrogen receptors: new actors in the plot of transcriptional
      regulation of genomic responses.

PMID- 12522669
TI  - TPD-TG-MS study of carbonate calcium hydroxyapatite particles.
AB  - Simultaneous temperature-programmed desorption, mass spectroscopy, and
      thermogravimetry (TPD-MS-TG) were carried out to explore the evolution process of
      H2O and CO2 from calcium hydroxyapatite particles containing carbonate ions of
      0.1-10.1 mass%. The TPD-MS curves of both H2O and CO2 exhibited two peaks:
      desorption of H2O and CO2 adsorbed on the particles below 600 degrees C, and
      liberation of H2O and CO2 in the crystals above 700 degrees C. The increase of
      carbonate ion content in the particles increased the weight loss in the TPD-TG
      curves.

PMID- 12522670
TI  - The cutting edge: strategies to enhance radiologist workflow in a
      filmless/paperless imaging department.

PMID- 12522675
TI  - Early stages of probable Alzheimer disease are associated with changes in
      platelet amyloid precursor protein forms.
AB  - Previous findings demonstrated an altered pattern of amyloid precursor protein
      (APP) forms in platelets of Alzheimer disease (AD) patients, compared both with
      healthy control subjects or patients with non-Alzheimer-type dementia. The
      present study aims to evaluate whether platelet APP form ratio (APPr) is altered
      in patients with early stage AD. We selected 40 patients with early stage AD and
      40 age-matched healthy controls. Compared with controls (mean+/-SD=0.91+/-0.3),
      mean APPr was decreased in AD (mean+/-SD=0.46+/-0.26, p<0.0001). Sixteen very
      mild AD patients (clinical dementia rating=0.5), identified among the AD group,
      showed a significant decrease of APPr values (mean+/-SD=0.50+/-0.3, p<0.0001).
      These findings indicate that alteration of APP processing in platelets is an
      early event and suggest that this assay might be of diagnostic value in
      differentiating mild AD from normal ageing.

PMID- 12522676
TI  - Differences in immune cell invasion into the cerebrospinal fluid and brain
      parenchyma during cerebral infusion of interleukin-1beta.
AB  - Cytokine-mediated inflammatory cell recruitment into the brain is a critical step
      in the response to diverse insults, including infection, trauma, and stroke.
      Hence, continous intra-cerebroventricular infusion of interleukin (IL)-1beta
      leads to an impressive cell invasion into the cerebrospinal fluid, as well as the
      brain parenchyma. Neither tumor necrosis factor-alpha nor IL-6 induced any
      significant cell invasion at all. However, the diverse immune cells
      (granulocytes, monocytes/macrophages) showed a different time course of invasion.
      Moreover, there was an association between the number of infiltrating immune
      cells and the infused IL-1 concentration. By analyzing intra-brain immune events,
      we demonstrated a time- and dose-dependent induction of intercellular adhesion
      molecule (ICAM)-1, whereas there were no differences for P-selectin, vascular
      cell adhesion molecule (VCAM)-1, and monocyte-chemotractant protein (MCP)-1,
      comparing vehicle and IL-1-infused animals. In conclusion, we assume IL-1beta to
      be a key cytokine for the granulocyte and monocyte recruitment into the central
      nervous system after various insults. However, granulocytes anticipate monocyte
      invasion.

PMID- 12522678
TI  - Cerebral vein thrombosis and mild hyperhomocysteinemia: three new cases.
AB  - Mild hyperhomocysteinemia is an established risk factor for deep vein thrombosis.
      We report three patients with cerebral vein thrombosis (CVT) in which the only
      risk factor we were able to identify was increased blood homocysteine levels and
      the C677T polymorphism in both alleles of the methylene tetrahydrofolate
      reductase MTHFR gene. We suggest that hyperhomocysteinemia should also be a risk
      factor for CVT. Since this condition can be effectively and safely corrected by
      drugs, we suggest that homocysteine levels should be routinely determined in
      patients with idiopatic CVT, and even mildly increased levels corrected
      pharmacologically, in the hope of reducing the risks associated with this
      condition.

PMID- 12522677
TI  - Intra-arterial ACNU and carboplatin versus intravenous chemotherapy with
      cisplatin and BCNU in newly diagnosed patients with glioblastoma.
AB  - Thirty glioblastoma patients treated at our institute between April 1998 and
      September 1999 were randomized in a two-arm study to receive carboplatin plus
      ACNU intraarterial (IA) chemotherapy (arm A) or cisplatin plus BCNU intravenous
      (IV) treatment (arm B). After the second course of chemotherapy and before the
      third cycle they also received concomitant radiotherapy, consisting of a median
      dose of 56.5 Gy. There were 3 (21.4%) partial responses and 11 (78.6%) disease
      stabilizations in group A. There were 5 (33%) partial responses and 10 disease
      stabilizations in group B. Time to tumor progression was 5.2 and 5.8 months for
      IA and IV treatment respectively. Median survival time was 18.3 months for arm A
      patients and 18.6 for arm B patients. Our IA chemotherapy schedule has produced
      no conclusive evidence of benefit compared with intravenous treatment. Moreover,
      its cost-benefit ratio is not good enough to justify its continued pursuit.

PMID- 12522679
TI  - Factor V Leiden mutation and patent foramen ovale in ischemic stroke.
AB  - We report a 47-years-old male with ischemic stroke, whose arteriographic and
      echocardiographic investigations did not reveal any steno-occlusive arterial
      disease or embolic source from the left cardiac chambers. A transesophageal
      echocardiogram showed a patent foramen ovale (PFO), whilst laboratory screening
      for coagulation abnormalities showed heterozygosity for factor V Leiden mutation.
      The significance of the association of PFO with factor V Leiden mutation is
      discussed as a possible cause of ischemic stroke through paradoxical embolism
      from a venous source. The high prevalence of these two conditions in the general
      population is emphasized and the indication for anticoagulant therapy is
      discussed.

PMID- 12522680
TI  - Switch to quetiapine in antipsychotic agent-related hyperprolactinemia.
AB  - Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are
      effective in treating psychotic symptoms, also in neurological disease.
      Hyperprolactinemia is a side effect related to antipsychotics that can cause
      galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis,
      decreased libido and sexual arousal, impotence, and anorgasmia, consequent to
      removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic
      dopaminergic receptor blockade in the tuberoinfundibolar tract.
      Hyperprolactinemia occurs more frequently during treatment with risperidone and
      olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to
      antipsychotic-relatedhyperprolactinemia is the following: reduction in
      antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or
      switch to another antipsychotic. We propose switching to quetiapine in
      symptomatic hyperprolactinemia related to antipsychotics and describe five cases.

PMID- 12522681
TI  - Radiation leukoencephalopathy associated with moderate hydrocephalus:
      intracranial pressure monitoring and results of ventriculoperitoneal shunting.
AB  - Delayed neurological sequelae of radiotherapy have several manifestations;
      leukoencephalopathy is one of the most common. Pathogenetic relationships between
      radiation leukoencephalopathy and other findings of diffuse radiation injury
      (brain atrophy and progressive ventriculomegaly) are not well defined. Moreover,
      no guidelines have been established for the treatment of hydrocephalus when
      associated with radiation leukoencephalopathy. Our study reports intracranial
      pressure (ICP) monitoring in two patients with radiation leukoencephalopathy with
      moderate hydrocephalus. High intraventricular mean pressure and high peaks were
      found, and marked improvement of clinical status after shunting was achieved.
      This study, although restricted to only two patients, shows that
      ventriculoperitoneal shunting insertion is useful in radiation-induced
      hydrocephalus, when ICP monitoring detects high mean pressure. A hypothesis is
      advanced concerning radiation-induced hydrocephalus with high ICP, emphasizing
      periventricular astrocytosis and its connections with cerebral compliance.

PMID- 12522682
TI  - Unusual association of sporadic olivopontocerebellar atrophy and motor neuron
      disease.
AB  - Sporadic olivopontocerebellar atrophy (OPCA) is a neurodegenerative disorder that
      presents a wide clinical spectrum. Motor neuron disease (MND) is characterized by
      a selective degeneration of motor neurons. A 60-year-old man developed slurred
      speech and unsteadiness of gait. He had also noticed difficulty in holding his
      head upright and shoulder weakness. The disease had a rapid progression. At the
      age of 63 years, magnetic resonance imaging supported a diagnosis of OPCA, and a
      diagnosis of MND was suggested by clinical and electrophysiological findings. He
      also had upward gaze palsy. A muscular biopsy showed sporadic ragged red and Cox
      deficient fibers. The present case could define a unique disorder, as the
      occasional occurrence of two degenerative disorders appears unlikely.

PMID- 12522683
TI  - A case of Kearns-Sayre syndrome with the 4,977-bp common deletion associated with
      a novel 7,704-bp deletion.
AB  - Mitochondria from a patient diagnosed with Kearns-Sayre syndrome (KSS) exhibited
      severely diminished cytochrome c oxidase activity and at least four mitochondrial
      DNA (mtDNA) species: 9%-11% of the fulllength mtDNA (16.6 kb), 70%-75% of a 11.7
      kb population (harboring the 4,977-bp common deletion), 2%-3% of a 10.5-kb
      population, and 12%-17% of a 8.9-kb population. The 8.9-kb mtDNA exhibited a
      secondary deletion that extended 7,704 bp from nucleotide 7,979 in the cox2 gene
      to nucleotide 15,683 in the cytb gene. To our knowledge, this is the first
      description of the presence of at least two large-scale deletions of mtDNA in
      KSS.

PMID- 12522684
TI  - A novel locus for autosomal dominant nonsyndromic hearing loss identified at
      5q31.1-32 in a Chinese pedigree.
AB  - Hearing impairment is an extremely heterogeneous disorder. A total of 35 loci and
      17 related genes for autosomal dominant nonsyndromic hearing loss have been
      identified. In a Chinese pedigree characterized by autosomal dominant inheritance
      with bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing
      impairment, the putative disease gene locus was localized to chromosome 5q31.1-32
      by a genome-wide scan. Fine mapping indicated that the disease gene was located
      within an 8.8-cM region between markers D5S2056 and D5S638, with a maximum two
      point logarithm of differences (LOD) score of 6.89 (theta = 0) at D5S2017. By the
      candidate gene approach, mutation screening of the DIAPH1 and POU4F3 genes at
      5q31 was performed. No mutation was found, suggesting that this is a novel
      deafness locus, which has been named DFNA42.

PMID- 12522685
TI  - Association of common missense changes in ELAC2 ( HPC2) with prostate cancer in a
      Japanese case-control series.
AB  - The recently identified prostate cancer susceptibility gene ELAC2 ( HPC2) harbors
      two common missense variants, a serine to leucine substitution at residue 217
      (Leu217) and an alanine to threonine substitution at residue 541 (Thr541). We
      genotyped the two variants in a Japanese cohort consisting of 350 prostate cancer
      patients 242 male population controls, and 114 male low-risk controls. Both
      missense alleles, Leu217 and Thr541, were carried at higher frequency in Japanese
      patients than in the controls (Leu217, P= 0.0012; Thr541, P = 0.0145), and the
      odds ratios associated with carrying these sequence variants were higher in
      Japanese than in Caucasians. Although the Leu217 and Thr541 variants of ELAC2 are
      less common in Japanese than in Caucasians, both variants confer significantly
      increased risk of prostate cancer in Japanese. Carriage of these variants was not
      associated with age at diagnosis, tumor stage, or tumor grade in these Japanese
      prostate cancer patients. The allele-specific pattern of risk observed in
      Japanese and familial Caucasian patients was qualitatively similar; however, the
      magnitude of that risk was considerably greater in Japanese than in Caucasians.

PMID- 12522686
TI  - Akaike's information criterion for a measure of linkage disequilibrium.
AB  - The extent and distribution of linkage disequilibrium ( LD) in humans is a
      current topic especially for gene mapping of complex diseases. Akaike's
      information criterion ( AIC) was applied to estimate LD and compared with other
      standard LD measures, D' and r(2). By comparison of an independent model (IM;
      linkage equilibrium) and a dependent model (DM; linkage disequilibrium), the
      parsimonious model is the one with the smaller AIC score. Therefore, the extent
      of LD by AIC is expressed as AIC( IM) -- AIC( DM)( AIC( LD)). A total of 39
      single-nucleotide polymorphisms on a 1.6-Mb region of chromosome 21 q22 were
      identified, and genotyped in 192 Japanese individuals. All possible pairs were
      analyzed to estimate LD and the analyses were compared. AIC( LD) became highly
      positive as the D' value increased and was negative at D' values of around 0.2.
      Because a negative value of AIC( LD) implies linkage equilibrium, D' values below
      0.2 should be regarded as linkage equilibrium. The LD estimate by AIC yielded
      results similar to those obtained by r(2), indicating that AIC( LD) would be
      useful for fine gene mapping.

PMID- 12522687
TI  - Interaction between the LDL-receptor gene bearing a novel mutation and a variant
      in the apolipoprotein A-II promoter: molecular study in a 1135-member familial
      hypercholesterolemia kindred.
AB  - Lipid and lipoprotein concentrations in plasma generally reflect complex
      influences of multiple genetic loci. Even an autosomal dominant disorder,
      familial hypercholesterolemia (FH), is characterized by phenotypic heterogeneity,
      as low-density lipoprotein (LDL) levels vary widely within the same pedigree.
      Molecular screening for LDL receptor ( LDLR) mutations among 75 patients with
      clinically apparent FH led to identification of a novel splice-site mutation
      (IVS14+1 G>A) shared by 14 patients. Genealogical research confirmed that all 14
      carriers were part of the same 1135-member pedigree with a common ancestor. The
      mutation resulted in an abruptly truncated LDLR protein, reducing functional LDLR
      activity by half in heterozygous carriers of the mutant allele. Of the 208
      members of the kindred who were screened for the presence of this LDLR mutation,
      we identified 94 carriers and 114 noncarriers. Nine principal apolipoprotein
      genes that might affect LDL cholesterol differentially according to LDL-receptor
      status were examined in this pedigree. Strikingly lower total cholesterol and LDL
      cholesterol values were observed among the majority of the LDLR mutation carriers
      who were simultaneously homozygous for the -265C variant of apoA-II (total
      cholesterol: 324 +/- 8 vs 244 +/- 19 mg/dl, P = 0.0015; LDL-cholesterol: 237 +/-
      8 vs 155 +/- 18 mg/dl, P = 0.0008). In vitro transfection assays showed that
      transcriptional activity of the apoA-II promoter was reduced by 30% in the -265C
      variant as compared with the -265T variant. We thus concluded that one variant of
      the apoA-II gene was associated with reduced plasma LDL cholesterol only in FH
      patients.

PMID- 12522688
TI  - Common variant of human NEDD4L activates a cryptic splice site to form a
      frameshifted transcript.
AB  - The ubiquitin ligase NEDD4L is a candidate gene for essential hypertension on
      both functional and genetic grounds. By targeting the epithelial sodium channel
      (ENaC) for degradation, NEDD4L is a significant determinant of sodium
      reabsorption in the distal nephron. Genetic linkage has been reported to a region
      of chromosome 18q harboring the gene, with phenotypes that include a rare
      orthostatic hypotension disorder, essential hypertension, and postural change in
      systolic blood pressure. A systematic search for genetic polymorphisms by
      resequencing exons and intron boundaries in 48 Caucasians yielded 38 variants.
      Among these, variant 13 is common, with either G (70%) or A (30%) as the last
      nucleotide of a putative exon 1. This mutation could affect the generation of a
      previously unrecognized splice isoform. In subsequent experiments, (1) we
      confirmed the presence of this putative isoform in both kidney and adrenals; (2)
      we established that variant 13-A leads to the systematic use of an alternative
      splice site, generating a transcript encoding a nonfunctional protein; and (3) we
      demonstrated differences in tissue-specific expression of the novel isoform
      relative to its previously reported counterpart. Variant 13-A precludes the
      formation of a transcript encoding a full-length Ca2+-dependent lipid-binding
      (C2) domain with very high evolutionary conservation among NEDD4L orthologs. A
      similar C2 domain in the paralogous NEDD4 gene plays a significant role in the
      transfer of its product to the apical membrane of epithelial cells. Differential
      function of NEDD4L isoforms could prove significant in blood pressure regulation
      through an effect on ENaC-dependent sodium reabsorption.

PMID- 12522689
TI  - Cloning, characterization, and chromosome mapping of the human GlcAT-S gene.
AB  - We report on the structure, map location, and tissue expression of the human
      GlcAT-Sgene. The gene covers approximately 85 Kb on chromosome 6 (6q13) between
      the D6S455 and D6S1673 markers. GlcAT-S is composed of four exons and encodes a
      324-amino-acid protein, which shows 89% homology with the rat glcat-s protein and
      is involved in the biosynthesis of the HNK-1 carbohydrate epitope on
      glycoproteins. Although GlcAT-Swas considered an interesting candidate gene for
      the RP25 locus, the absence of any pathogenic mutations in probands of RP25
      linked families ruled out that candidacy.

PMID- 12522690
TI  - Identification of a novel human DDX40gene, a new member of the DEAH-box protein
      family.
AB  - The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA
      metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have
      cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box
      polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative
      779-amino-acid protein. Sequence analysis of the cDNA product revealed that it
      contained a DEAH (Asp-Glu-Ala-His) sequence motif and other conserved motifs. The
      DDX40 protein shared 53% and 43% amino acid identity with human DDX8 and yeast
      Drh1, respectively, in the conserved region. Northern blot analysis showed that
      DDX40 was expressed ubiquitously in the eight tissues examined, implying a
      general physiological function of the protein. We speculate that, like other
      members of the DExH/D-box superfamily, DDX40 may play roles in pre-mRNA splicing,
      ribosome biogenesis and other RNA processing functions.

PMID- 12522691
TI  - Identification of single-nucleotide and repeat polymorphisms in two candidate
      genes, interleukin 4 receptor (IL4RA) and signal transducer and activator of
      transcription protein 6 (STAT6), for Th2-mediated diseases.
AB  - We report here the identification of 26 single-nucleotide polymorphisms (SNPs)
      spanning a total of 147 kb in two candidate genes, IL4RA and STAT6, for atopic
      disorders. Fourteen novel SNPs were found in our population. We also report the
      identification of three novel polymorphic (CA) repeat regions in these genes. No
      insertion/deletion polymorphisms in AluY elements were detected. The encoded
      proteins of these two genes are part of a single signaling pathway, and
      therefore, functional polymorphisms in these genes could potentially lead to
      higher risk and susceptibility to atopic disorders. We also examined the allelic
      frequency and haplotypes of these polymorphisms in a control population. These
      data will be potentially useful for association studies designed to investigate
      the role of these genes in atopic disorders such as asthma, eczema, and allergic
      rhinitis. This is the first report on the polymorphic content of these two genes
      in the Indian population.

PMID- 12522692
TI  - Connexin26 gene ( GJB2): prevalence of mutations in the Chinese population.
AB  - The connexin26 gene ( GJB2) has been shown to be responsible for DFNB1 and DFNA3
      (Autosomal Recessive Hereditary Nonsyndromic Deafness Locus 1 and Autosomal
      Dominant Hereditary Nonsyndromic Deafness Locus 3). Two hundred ten independently
      ascertained Chinese probands with nonsyndromic hearing loss (NSHL) were evaluated
      for mutations in GJB2, including 43 probands from families with more than one sib
      with NSHL, likely indicating dominant inheritance, and sporadic cases of NSHL,
      compatible with recessive inheritance. Of the 210 probands, 43 (20%) were
      homozygous or heterozygous for mutations in GJB2. Four different mutations were
      identified: 35delG, 109G-A, 235delC, and 299-300delAT. It was confirmed that GJB2
      mutations are an important cause of hearing loss in this population. Of these
      four mutations, 235delC was the most prevalent at 93%; yet the 35delG mutation,
      which is the most common GJB2 mutation in Caucasian subjects (Europeans and
      Americans), was found in low frequency in the present study. It appears from our
      limited data and reports from other East Asians that 235delC is the most
      prevalent GJB2 mutation in these populations. GJB2 mutations are consistent with
      ethnic predilections.

PMID- 12522693
TI  - Primary Burkitt-like lymphoma presenting as a solitary rectal polyp in a child:
      case report.
AB  - Primary rectal lymphoma in childhood is rare. We report a case in a 10-year-old
      boy who presented with rectal bleeding and a single rectal polyp. Histologic
      examination, immunophenotyping and molecular genetic study of the polyp showed a
      diffuse B-cell lymphoma, Burkitt-like type. The literature on this topic is
      reviewed and pathologic examination of childhood rectal polyps is emphasized.

PMID- 12522694
TI  - Patency of infrarenal aortic side branches determines early aneurysm sac behavior
      after endovascular repair.
AB  - In this study we sought to determine whether initial abdominal aortic aneurysm
      (AAA) sac anatomy, morphology, and side branch patency influence changes in
      aneurysm size and development of endoleak following endovascular repair. A
      blinded, retrospective review of preintervention CT scans and angiograms was
      conducted on 70 consecutive patients treated for infrarenal AAA (mean size 6.0 +/
      0.8 cm) by AneuRx stent-graft exclusion. Initial AAA diameter and side branch
      (inferior mesenteric artery [IMA], lumbar artery pair) patency, AAA clot/sac
      diameter ratio, wall thrombus and calcification distributions, attachment site
      anatomy, endograft size, and other clinical parameters were correlated with
      postoperative persistent side branch patency, presence of type II endoleak, and
      change in AAA diameter (increase/decrease ? 5 mm) using contingency table
      analyses. Patients underwent CT scanning and/or color duplex imaging at 1 month
      and at 3 (with endoleak) or 6 (without) month intervals postoperatively with 50
      patients followed beyond 6 months (mean follow-up 11 +/- 7 months). The majority
      of patients possessed patent side branches prior to intervention (lumbar [n = 60,
      86%], IMA [n = 45, 64%]). Development of type II endoleak or persistence of side
      branches could not be predicted (p > 0.05) from preoperative AAA side branch
      patency or any of the other initial anatomic AAA variables. On serial post-repair
      CT or duplex cans, 42% (19/45) of IMAs and 27% (16/60) of lumbar artery pairs
      remained patent. For patients followed beyond 6 months, type II endoleaks
      persisted in half (13/25) of the patients with patent side branches with roughly
      equal proportions fed by IMA and lumbar sources. Persistent side branches or
      presence of type II endoleak was associated with AAA expansion or the failure of
      aneurysm size diminution after endografting (p <0.01). Aneurysm sac regression
      was most likely in the absence of endoleak and patent side branches. We conclude
      that persistent side branch patency not only fuels development of type II
      endoleak but also influences early aneurysm sac behavior after endovascular
      repair. Optimal anatomic patient selection for endografting may not be possible
      on the basis of our initial experience, since preoperative AAA variables did not
      predict persistence of side branches or type II endoleaks.

PMID- 12522695
TI  - Acute occlusive mesenteric ischemia: surgical management and outcomes.
AB  - Acute mesenteric ischemia secondary to arterial occlusion (AMI) remains a highly
      lethal condition. To examine recent trends in management and associated outcomes,
      we examined our institutional experience over a recent 10-year period. All
      patients treated for AMI between January 1990 and January 2000 were identified
      (76 patients, 77 cases) and their medical records examined. At presentation, 64%
      demonstrated peritonitis and 30% exhibited hypotension. The interval from symptom
      onset to treatment exceeded 24 h in 63% of cases. Etiology was mesenteric
      thrombosis in 44 patients (58%) and embolism in 32 patients (42%). Thirty-five
      patients (46%) had prior conditions placing them at high risk for the development
      of AMI including chronic mesenteric ischemia (n = 26) and inadequately
      anticoagulated chronic atrial fibrillation (n = 9). Surgical management consisted
      of exploration alone in 16 patients, bowel resection alone in 18 patients, and
      revascularization in 43 patients, including 28 who required concomitant bowel
      resection. Overall, intestinal necrosis was present in 81% of cases.
      Perioperative mortality was 62% and long-term parenteral nutrition (TPN) was
      required in 31% of survivors. Peritonitis (odds ratio [OR] 9.4, 95% confidence
      interval [CI] 1.6, 54.0; p = 0.012 and bowel necrosis (OR 10.4, CI 1.9, 56.3; p =
      0.007) at presentation were independent predictors of death or survival dependent
      upon TPN. We conclude that AMI remains a highly lethal condition due in large
      part to advanced presentation and inadequate recognition and treatment of
      patients at high risk.

PMID- 12522696
TI  - The benefits of carotid endarterectomy in the octogenarian: a challenge to the
      results of carotid angioplasty and stenting.
AB  - Proponents of carotid angioplasty and stenting (CAS) believe that this technique
      would be preferred over carotid endarterectomy (CEA) for the high-risk patient.
      Presumably this would include patients over 80 years of age. However, a recent
      large series of patients undergoing CAS revealed a 16% incidence of nonfatal
      strokes and deaths for patients over the age of 80; these results were
      significantly worse than those for younger patients undergoing CAS. The objective
      of this study was to reassess results of CEA in patients over 80, and to compare
      surgical results with the published results of CAS in this patient group. A
      review was conducted of a prospectively maintained database of all carotid
      surgery performed at our institution. Primary CEA that took place from 1997
      through 1999 were included for analysis (n = 698). Our institutional results were
      compared with representative results from a recently published large series of
      CAS. Our analysis showed that CEA can be performed safely in the octogenarian,
      and results are equivalent to those of younger patients. CEA appears to have
      significantly better results in the octogenarian than CAS. The reasons for the
      poor outcomes of CAS in the octogenarian are unclear. The results of CAS in the
      older patient population are worrisome, and this "less invasive" technique may
      prove to be an inferior alternative in this patient group.

PMID- 12522697
TI  - Comparison of vascular smooth muscle cell apoptosis and fibrous cap morphology in
      symptomatic and asymptomatic carotid artery disease.
AB  - The biological cascades that lead to carotid plaque disruptions and symptoms are
      largely unknown. Certain cellular events within the plaque might be responsible
      for destabilizing the plaque, though the popular belief is that the plaque size
      is directly related to symptoms. The aim of our study was to assess the
      morphology of the fibrous cap and apoptosis in the plaque and compare these two
      pathological features in symptomatic and asymptomatic carotid artery disease. Our
      work was carried out in plaques obtained following carotid endarterectomy
      performed for symptomatic disease (including hemispheric transient ischemic
      attacks, amaurosis fugax, or stroke) or asymptomatic high-grade severe stenosis.
      Scion images of Gomori's stained sections were used to measure fibrous cap
      thickness and area. TUNEL assay was performed to assess the extent of apoptosis.
      The results indicated that the area of the fibrous cap did not significantly
      correlate with the presence of symptoms. There was a higher percentage of
      apoptotic nuclei and the thinner fibrous cap in symptomatic plaques than in
      asymptomatic plaques. This finding suggests that these factors might be involved
      in destabilizing plaque, causing rupture and leading to symptomatic carotid
      disease.

PMID- 12522698
TI  - Determining patient preference for treatment of extracranial carotid artery
      stenosis: carotid angioplasty and stenting versus carotid endarterectomy.
AB  - Revascularization of extracranial carotid artery stenosis (ECAS) continues to be
      the subject of spirited academic debate. Conflicting studies in the literature
      have fostered uncertainty among patients choosing between CEA and CAS. We
      obtained preference-based utilities from prospective patients being evaluated for
      ECAS and incorporated them into a decision analytic model. Patients being
      evaluated for ECAS in an outpatient setting were interviewed prior to their
      initial visit with a vascular surgeon. Patient preference data were elicited
      using probability trade-off (PTO) assessment and time trade-off (TTO) method.
      Decision analysis was performed to compare CEA with CAS. Morbidity and mortality
      rates were obtained from recent literature reports from the same institution. Our
      results showed that when patients are informed, they prefer and will more often
      choose CEA over CAS for revascularization of ECAS. Among patients preferring CAS,
      they expect no more than a 46% increase in the rate of stroke and/or death.
      Future clinical studies on true stroke rates for CAS will be required to further
      refine this analysis.

PMID- 12522699
TI  - Technical success from endovascular aneurysm repair in the post-marketing era: a
      multicenter prospective trial.
AB  - Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was
      accomplished by review of a multicenter, prospective trial involving 46 centers
      and 163 patients. A second cohort of patients (n = 350) treated with the AEG
      under a controlled-use interval prior to the prospective trial was simultaneously
      evaluated. Technical success in both groups of patients (96.9% and 97.4%,
      respectively) was similar to what was reported in pre-market clinical trials.
      Operative implantation complications unique to the AEG included graft limb
      stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on
      hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%,
      jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8
      and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract
      jacket in 1.8 and 0.5% of patients involved in the multicenter trial and
      controlled-use interval, respectively. One of four patients undergoing conversion
      in the prospective trial had graft misdeployment as a mode of failure. Three were
      converted for access failure. The 30-day mortality rate in the prospective trial
      was 3.7%. Interventions to resolve implantation-related events included stenting,
      guide catheter manipulations, wire exchanges, and delivery catheter disassembly.
      These interventions were successful in virtually every case. Open surgical
      procedures were not needed to correct these operative problems. Results from this
      study demonstrate excellent technical success with the AEG in the post-market
      era. Interventions to resolve implantation complications, when utilized, are
      highly successful in facilitating AEG implantation and providing technical
      success.

PMID- 12522700
TI  - Optimal operative strategies in repair of juxtarenal abdominal aortic aneurysms.
AB  - In an effort to identify preoperative and perioperative factors impacting outcome
      in repair of juxtarenal abdominal aortic aneurysm (JRAAA), hospital records and
      CT scans (for calcification, intraluminal thrombus, and aortic diameter) of all
      patients undergoing JRAAA repair over the past 10 years were reviewed. The 87 men
      and 25 women had a mean age of 72, and a mean maximal aortic diameter of 6.2 cm.
      Renal artery stenosis (RAS) and iliac disease were present in 13 (11%) and 40
      patients (35%), respectively. Comorbidities included coronary artery disease (n =
      49, 44%), COPD (n = 28, 25%), diabetes mellitus (n = 10, 9%), and preoperative
      renal insufficiency (PRI; Cr >1.4 mg/dL; n = 14, 12%). A midline incision was
      used in most of the patients (n = 98, 88%). The proximal aortic clamp was placed
      in the supraceliac (SC) position in 92 (82%) patients, and directly above one or
      both renal arteries in 20 (18%) patients. The overall mortality was 6% (n = 7).
      Cardiac complications occurred in 26 patients (23%); pulmonary, in 22 (20%);
      renal, in 14 (12%); and gastrointestinal, in 10 (9%). No patient experienced
      mesenteric ischemia. Mean elevation in creatinine was greater in patients with
      PRI (1.8 mg/dL vs. 0.13 mg/dL, p = 0.04). Mean blood loss (EBL) was 2701 +/- 189
      cc, and mean LOS was 16.1 +/- 1.7 days. Age >70 was associated with increased
      length of stay (LOS) (12.1 days vs. 18.6 days, p = 0.05) and higher mortality (0
      vs. 10%, p = 0.02); otherwise there were no significant relationships between pre
      and perioperative parameters and any of the measured outcomes including death,
      postoperative RI, and LOS. Preferential SC clamping may substantially reduce
      complications of JRAAA repair (such as mesenteric and renal ischemia) related to
      proximal cuff disease, but cannot overcome the deleterious affects of advanced
      age and PRI.

PMID- 12522701
TI  - Risk factors associated with infection of lower extremity revascularization:
      analysis of 365 procedures performed at a teaching hospital.
AB  - Infection of arterial reconstructions is associated with high rates of mortality
      and limb loss despite optimal treatment. Lower extremity revascularization
      procedures performed at a teaching hospital were reviewed to identify risk
      factors associated with wound infection. Medical records, postoperative infection
      surveillance forms, and a computerized vascular registry for lower extremity
      revascularizations involving a common femoral or more distal artery during a 3
      year period were reviewed. There were 335 bypass operations (184 femoral-distal,
      36 popliteal-distal, 17 aortofemoral, 13 femorofemoral, 11 axillofemoral, 74
      graft revisions) and 30 other vascular procedures (arterial thrombectomy or
      endarterectomy). Factors analyzed included age, gender, diabetes mellitus,
      dialysis dependence, malnutrition, obesity, ipsilateral foot ulcer or gangrene,
      separate admissions within the month preceding surgery, length of hospital stay
      before surgery, length of operation, wound hematoma requiring reoperation, vein
      or prosthetic grafts, or redo surgery. Risk factors commonly thought to increase
      wound infection following lower extremity revascularizations, such as diabetes,
      obesity, renal failure, redo surgery, and prosthetic grafts, did not predict this
      complication in this series. Given the correlation of operative time with
      infection, efforts to minimize operative time by "double-teaming" staff
      participation in teaching cases may decrease infection rates, although this is
      speculative. Vascular services should institute strategies to ensure that
      appropriate prophylactic antibiotics are administered in a timely fashion before
      lower extremity revascularizations.

PMID- 12522702
TI  - Infectious and ischemic complications from percutaneous closure devices used
      after vascular access.
AB  - The introduction of percutaneous closure devices (PCDs) to seal arteriotomy sites
      following percutaneous vascular access (PVA) can lead to greater complications
      than those with manual compression. The aim of this study was to compare
      complications and outcome between patients requiring surgery after receiving a
      PCD and those undergoing standard manual compression. This retrospective study
      evaluated 56 patients (mean age, 63 years) requiring surgical intervention from
      January 1, 1998 to April 30, 2002, following complications of PVA. Operative
      indications were pseudoaneurysm, hemorrhage, infectious complications, and limb
      ischemia. Patients were divided into two groups for comparison: group I (n = 15,
      PCD) and group II (n = 41, no PCD). In group 1 patients there were 18 limbs in
      which 20 Perclose devices were used and 1 limb in which a Duett device was used.
      From the outcomes in these two groups we concluded that patients undergoing
      surgical intervention following complications of PVA are at a significantly
      increased risk for infectious and ischemic complications and require more complex
      vascular repair when percutaneous closure devices are used.

PMID- 12522703
TI  - Complication rates of percutaneous brachial artery access in peripheral vascular
      angiography.
AB  - The brachial artery has been considered a secondary choice for percutaneous
      access due to reported increased complication rates compared to femoral access
      despite potential advantages in peripheral vascular disease (PVD) patients. A
      prospectively collected database of 1326 PVD patients undergoing angiography with
      percutaneous brachial access between January 1, 1990 and December 31, 1999 was
      retrospectively reviewed. All patient charts with coded brachial pathology during
      this time period were reviewed to ensure complete data capture. The protocol for
      patients undergoing brachial access included a vascular surgery evaluation after
      each angiogram and telephone follow-up by a nurse at 24 hr. During this 10-year
      period, a percutaneous brachial artery approach was used to perform 1084
      angiograms in men and 242 angiograms in women. A subset of 111 patients had
      multiple studies (range: 2 to 7) via brachial access without complication. Rates
      of failed access (2.1% female vs. 0% male, p <0.001) and brachial thrombosis
      (1.24% female vs. 0.28% male, p <0.04) were significantly higher in women. The
      complication rate for all patients was 1.28%. Percutaneous brachial access for
      angiography can be safely and repetitively performed in PVD patients, although
      women have an increased risk of thrombosis and failed access. The brachial
      approach allows early ambulation and discharge, and can be considered a primary
      choice for diagnostic angiographic access.

PMID- 12522704
TI  - Major lower extremity amputation in an academic vascular center.
AB  - Major lower extremity amputations continue to be performed despite an aggressive
      policy of revascularization. Factors leading to amputation were analyzed to
      determine whether a reduction in the limb loss rate is possible. A retrospective
      analysis of a prospectively maintained vascular registry was performed to
      identify patients undergoing above-knee amputation (AKA), below-knee amputation
      (BKA), and lower extremity revascularization (LER) for limb salvage between
      January 1, 1999 and January 1, 2002. Patient demographics, comorbidities,
      insurance carriers, and indications for operative intervention were analyzed.
      Greater than one-half of all major lower extremity amputations are performed in
      patients who have failed attempts at revascularization or who are not candidates
      for LER due to anatomic factors. However, one-quarter of eventual amputees
      present very late to the vascular surgeon with extensive gangrene or infection
      that precludes limb salvage. Prompt patient referral and treatment may improve
      outcome in this group of patients. In our study, insurance issues did not appear
      to affect treatment. Renal failure continues to play a major role in limb loss.

PMID- 12522705
TI  - Methicillin-resistant Staphylococcus aureus infection does not adversely affect
      clinical outcome of lower extremity amputations.
AB  - Methicillin-resistant Staphylococcus aureus was first identified in isolation in
      Europe during the 1960's. Now widespread throughout the world, infection with
      this organism has emerged as a major problem in surgical practice. However, it
      remains debatable whether MRSA is more virulent than methicillin-susceptible
      strains. We have reviewed our most recent 4-year experience of lower extremity
      amputations to examine the influence of MRSA and non-MRSA infection on clinical
      outcome. During the past 4 years, 165 patients underwent lower extremity
      amputation for SVS/ISCVS category III acute limb ischemia and grades II and III
      chronic limb ischemia. Forty-five had documented MRSA infection, while 57
      patients had documented infection with other flora. All patients were treated
      with appropriate sensitivity-specific antibiotics and aggressive wound care. No
      significant differences were noted in the level of primary amputation required by
      the two groups. Similarly, no significant differences were noted in either number
      of revisions or revision to higher-level amputation, time to heal, hospital
      length of stay, or 30-day morbidity and mortality rates. Our results demonstrate
      that MRSA infection does not adversely affect clinical outcome in patients
      undergoing lower extremity amputations. Appropriate treatment of infections with
      sensitivity-specific antibiotics, thorough wound debridement, and aggressive
      wound monitoring should be routine in all patients, regardless of bacterial
      flora.

PMID- 12522706
TI  - Surgical treatment of coronary subclavian steal syndrome with carotid subclavian
      bypass.
AB  - Coronary subclavian steal syndrome (CSS) results from proximal subclavian artery
      occlusive disease causing reversal of flow in an internal mammary artery used as
      conduit for coronary artery bypass leading to myocardial ischemia. Although
      percutaneous transluminal angioplasty and stent (PTAS) for subclavian lesions has
      been successful, it is not always feasible. In this study, the results of carotid
      subclavian bypass (CSB) for symptomatic CSS due to subclavian occlusion and
      stenosis not amenable to PTAS were analyzed. The records of patients undergoing
      CSB for CSS between 1991 and 2001 were reviewed. Patients with lesions not
      amenable to angioplasty or stent were selected for CSB. Degree of preoperative
      myocardial ischemia was stratified according to New York Heart Association
      classification. Graft patency was analyzed by life-table methods. Our results
      showed that CSB for treatment of symptomatic CSS can be performed safely with
      excellent mid-term durability. In the setting of proximal subclavian artery
      disease not amenable to PTAS, CSB provides an acceptable means of treatment for
      symptomatic CSS.

PMID- 12522707
TI  - Orthopaedic Specialist Registrar training and attitudes to spine surgery in the
      United Kingdom: reasons for poor recruitment and suggestions for improvement.
AB  - In order to improve the provision of spinal surgery in the United Kingdom, the
      number of Specialist Spinal Surgeons and Surgeons with an Interest in Spinal
      Surgery needs to increase by 25% from the existing 175 surgeons. A survey of
      Specialist Orthopaedic Registrars was performed, which quantifies the predicted
      shortfall in the number intending to practise spinal surgery. The attitudes
      towards and perceptions of this field were obtained to identify factors that
      could be discouraging an interest in spine surgery.

PMID- 12522708
TI  - Muscle force evaluation and the role of posture in human lumbar spine under
      compression.
AB  - Using two nonlinear finite element models of the lumbar spine, the concept of
      optimal posture is explored by minimizing the segmental sagittal moments required
      for the equilibrium of the passive lumbar spine under a total of 2800 N axial
      compression while varying the pelvic tilt and lumbar lordosis. The redundant
      active-passive system is subsequently solved for this posture using a novel
      kinematics-based muscle calculation algorithm along with minimization approach.
      Some flattening in the lumbar spine substantially reduces the required moments
      and internal passive shear forces under 2800 N axial compression force. Small
      muscle forces are calculated for this optimal posture. The role of flattening in
      the lumbar lordosis and posterior pelvic tilt in diminishing the lumbar muscle
      activities in neutral postures is demonstrated. Without such changes in posture,
      the required moments probably exceed the moment-generating capability of local
      lumbar muscles. Consideration of such active-passive synergy and lack of its
      restriction may prove crucial in many activities. Moreover, a kinematics-based
      algorithm is proposed for the solution of spinal redundancy that fully accounts
      for the existing passive-active synergy while simultaneously satisfying all
      kinematics and equilibrium conditions along the length of the spine.

PMID- 12522709
TI  - Anterior fixation in the osteoporotic spine: cut-out and pullout characteristics
      of implants.
AB  - A new concept for the anchorage of anterior fixation implants in the osteoporotic
      thoracic and lumbar spine is presented. The SpiralBlade has been proposed as a
      suitable device for use in the osteoporotic spine, due to its broad, flat
      surface, which should provide resistance against cut-out of the implant through
      the vertebral body under dynamic loading. The cut-out and pullout characteristics
      of this implant were tested. The SpiralBlade was tested with and without a
      supplementary insertion guide screw. Two other commercial implants were tested
      for comparison: the VentroFix and the MACS-TL HMA (hollow monoaxial) screw. All
      implants were tested in osteoporotic human cadaveric vertebrae, using a modified
      in vitro testing protocol which simulated a full corpectomy model. Dynamic cyclic
      loading of 100 N, 200 N and 400 N was applied to the implant for 1000 cycles at
      each load level, and the subsidence of the vertebral body relative to the implant
      was measured. Following cyclic testing, the pullout strength of the implant was
      measured. No significant differences were found in the cut-out performance
      between the SpiralBlade with guide screw and the VentroFix. The SpiralBlade
      inserted without a guide screw was prone to cutting-out and a substantial loss of
      angular alignment of the vertebral body. Cut-out of the HMA screw was
      significantly greater than with the other implants. Two HMA screws fractured
      during testing. The VentroFix, with an average pullout force of 1166 N, has a
      significantly higher resistance to pullout than the SpiralBlade with guide screw
      (417 N), the SpiralBlade (332 N) and the Aesculap HMA screw (298 N). The
      SpiralBlade may be an alternative to anterior screw fixation in the osteoporotic
      spine, offering the same cut-out resistance with one implant rather than two
      screws.

PMID- 12522711
TI  - Hemi-epiphysiodesis for unclassified congenital scoliosis: immediate results and
      mid-term follow-up.
AB  - Complex spinal anomalies involved in congenital scoliosis consist of a jumble of
      vertebral defects. Progressive scoliotic curves are frequently encountered in
      these patients. We evaluated the results of hemi-epiphysiodesis for this patient
      population. A series of ten patients with unclassified scoliosis, involving
      multiple hemivertebrae and/or bars, was reviewed retrospectively. Hemi
      epiphysiodesis was the primary treatment in all patients. Mortality,
      complications and wound healing problems did not occur. The average Cobb angle
      for all patients changed from 54 degrees (range: 40 degrees -74 degrees),
      preoperatively, to 58 degrees (range: 30 degrees -104 degrees), postoperatively.
      Applying the criterion of a minimum change of 20 degrees, to take into account
      measurement variability, an epiphysiodesis effect was achieved in two procedures,
      progression was arrested in six procedures and failure occurred in two
      procedures. The mean rate of Cobb angle change per annum decreased from 2.9
      degrees (range: -35 degrees to 14 degrees), preoperatively, to 2.4 degrees
      (range: -4 degrees to 13 degrees), following surgery. Repeat surgery was
      necessitated by coexisting progressive kyphosis and pseudoarthrosis in one
      patient, and involved extension of primary epiphysiodesis in two patients. A mean
      intervention-free period of 58 months was established. These results suggest that
      hemi-epiphysiodesis stabilized the unclassified congenital scoliosis. Being under
      5 years of age, having a thoracolumbar curve location, and the absence of
      coexisting kyphosis were found to be associated with a more favorable outcome.

PMID- 12522710
TI  - The reliability of quantitative analysis on digital images of the scoliotic
      spine.
AB  - Although analysis of scoliotic deformity is still studied extensively by means of
      conventional roentgenograms, computer-assisted digital analysis may allow a
      faster, more accurate and more complete evaluation of the scoliotic spine. In
      this study, a new computer-assisted measurement method was evaluated. This method
      uses digital reconstruction images for quantitative analysis of the scoliotic
      spine. The aim of the current study was to determine the reliability of the
      computer-assisted measuring method, which was done by establishing coefficients
      of repeatability for a variety of measurements. Measurements were carried out by
      five observers on 30 frontal and 10 lateral scoliotic digital reconstruction
      images. Each image was measured on three separate occasions by placing anatomical
      vertebral landmarks and drawing lines with a computer pointing device. The
      computer then calculated a number of geometrical shape parameters from scale
      calibration, landmarks and lines. The intra- and interobserver results were
      subjected to an analysis of variance to assess the level of agreement, and the
      means and standard deviations were calculated. The coefficient of repeatability
      (CR) was taken to be equal to two standard deviations. The mean intraobserver CR
      was found to be 3.1 degrees for the Cobb angle on the frontal digital image and
      3.3 degrees for the kyphosis Cobb angle on the lateral overview. The mean
      difference in the intraobserver CR of the Cobb angle between measurements made by
      placing landmarks and those made by drawing lines was not statistically
      significant (P>0.05). The mean intraobserver CR for the other parameters can be
      summarized as follows: for lateral deviation it was 0.8 mm, for axial rotation
      4.0 degrees and for length of the spine 3.3 mm. The interobserver bias was
      negligible. It can be concluded that the reliability of our new method for
      quantifying geometrical variables on digital reconstruction images is better than
      measurements on conventional roentgenograms in previously published reports. The
      presented method is therefore considered to be more accurate for research of
      spinal deformities and more adequate for clinical management of scoliosis.

PMID- 12522712
TI  - No relationship exists between the correction of the thoracic and the lumbar
      curves after selective thoracic fusion for adolescent idiopathic scoliosis King
      type II.
AB  - In this study we focus on idiopathic scoliosis with a primary thoracic curve and
      a secondary lumbar curve. We were interested in how the lumbar curve corrects
      following selective thoracic fusion and whether one can explain or predict the
      behaviour of the lumbar curve. In the literature it is said that, if the lower
      level of fusion is properly selected, the lumbar curve spontaneously corrects to
      balance the thoracic curve after selective thoracic fusion. Most authors have
      assumed a mechanism whereby improvement of the lumbar curve occurs through
      counterbalancing the surgical correction of the thoracic curve. The correction of
      the lumbar curve is said to echo the correction obtained for the thoracic curve.
      Because of these hypotheses, we postulate there should be a correlation between
      the correction of the lumbar and the thoracic curves of a scoliosis. To validate
      this hypothesis, we performed a retrospective study on 27 patients with King type
      II adolescent idiopathic scoliosis treated by selective thoracic fusion. The mean
      preoperative Cobb angles were 54 degrees for the thoracic curve and 34 degrees
      for the lumbar curve. Postoperatively they were 31 degrees and 22 degrees
      respectively. Using Pearson correlation analysis, we found no significant
      correlation between the relative corrections of the individual thoracic and
      lumbar curves. Moreover, there was a decrease in the correlation between the
      thoracic and lumbar curve after operation (preoperative R=0.787, postoperative
      R=0.364). These results show that the correction of the lumbar curve is not a
      reflection of the thoracic correction. The exact mechanism by which the lumbar
      spine corrects remains to be elucidated.

PMID- 12522713
TI  - The effect of the Relton-Hall operative frame on trunk deformity in adolescent
      idiopathic scoliosis.
AB  - The prone operative position affects the geometry of the scoliotic spine.
      However, the literature provides little information concerning the effect of
      operative position on the scoliotic trunk geometry. This study compared the trunk
      deformity of 31 adolescent idiopathic scoliosis patients in two standardized
      positions: standing and prone on a Relton-Hall frame. The geometry of the trunk
      was assessed using 11 magnetic sensors placed on anatomical landmarks. Eight
      geometric indices of the trunk were compared using paired Student t-tests
      (alpha=0.01). The transverse rotation of shoulders, the coronal rotation of
      shoulders, the lateral shift of C7 with respect to S1, and the thoracic and
      lumbar angles of trunk rotation assessed in the operative position did not show
      any significant change compared to the standing position. Therefore, operative
      positioning using the Relton-Hall frame did not lead to an overall reduction in
      the scoliotic trunk deformity. Modifications to the Relton-Hall frame are
      required for optimal presurgical correction of the scoliotic trunk deformity.

PMID- 12522714
TI  - Clinical outcome and radiographic results after operative treatment of
      Scheuermann's disease.
AB  - The aim of this prospective study was to evaluate radiographic findings, patient
      satisfaction and clinical outcome, and to report complications and
      instrumentation failure after operative treatment of Scheuermann's disease using
      a combined anterior and posterior spondylodesis. The loss of sagittal plane
      correction after removal of the posterior instrumentation was analysed. The
      indication for surgery was a thoracic kyphosis greater than 60 degrees in
      adolescents and adults with persistent back pain, which failed to respond to
      conservative treatment. Thoracic kyphosis and lumbar lordosis angles were
      measured by the Cobb method at preselected time points and at final follow-up.
      Sagittal plane alignment was measured as translation. The validated Scoliosis
      Research Society Instrument (SRSI) questionnaire was sent to all patients at
      follow-up. P-values were calculated using the Wilcoxon signed rank test (P<0.05
      is significant). Between October 1987 and August 1999, 23 consecutive patients
      underwent operative treatment. The median follow-up was 75 months (range 25-126
      months). Median preoperative thoracic kyphosis was 70 degrees (range 62 degrees
      78 degrees) and median preoperative lumbar lordosis was 68 degrees (range 54
      degrees-84 degrees). Immediate postoperative median thoracic kyphosis was 39
      degrees (range 28 degrees-54 degrees) (P<0.05) and immediate postoperative median
      lumbar lordosis was 49 degrees (range 35 degrees-63 degrees) (P<0.05). These
      significant corrections were maintained at early follow-ups conducted 1 year and
      2 years postoperatively. At final follow-up, the median thoracic kyphosis had
      significantly increased, to 55 degrees (range 36 degrees-65 degrees) (P<0.05
      relative to immediate postoperative value), and the median lumbar lordosis had
      increased to 57 degrees (range 44 degrees-70 degrees) (P<0.05). The late
      deterioration of correction in the sagittal plane was mainly caused by removal of
      the posterior instrumentation, and occurred despite radiographs, bone scans and
      thorough intra-operative explorations demonstrating solid fusions. The median
      SRSI score was 83 points (range 55-106). There was no significant correlation
      between the radiographic outcome and the SRSI score (P>0.05). Our series showed
      relatively fair outcome after operative treatment in Scheuermann's disease.
      Therefore, the indication for surgery in patients with Scheuermann's disease can
      be questioned.

PMID- 12522715
TI  - Observations on the safety and efficacy of surgical decompression for lumbar
      spinal stenosis in geriatric patients.
AB  - This retrospective study examines the results of surgical decompression of the
      lumbar spinal canal in 122 geriatric patients (age range 75-89 years) treated
      under general anesthesia by the same surgeon between the years 1990 and 1999.
      Patient demographics, perioperative complications, pain profiles before surgery
      and at the time of data collection (December 2000), as well as overall mortality
      were recorded. One hundred and twenty-two patients were studied. The average age
      at the time of surgery was 78.8 years (range 75-89 years). No perioperative
      deaths were recorded. The mean time elapsed from surgery until patient follow-up
      was 45.7 months (range 12-119 months). Fourteen patients had died at the time of
      patient follow-up (December 2000). When compared to pain experienced before
      surgery, at the time of the interview a significant (P<0.0001) improvement in low
      back and radicular pain as well as in the ability to perform daily activities
      (dressing, washing, getting out of bed and walking) was described. We conclude
      that, for geriatric patients rated as physical status I-II (>75 years) under the
      American Society of Anesthesiologists (ASA) classification, surgical release of
      lumbar spinal stenosis is a safe and effective treatment option. However, the
      suitability of ASA III patients requires further investigation.

PMID- 12522716
TI  - The significance of spinal canal dimensions in discriminating symptomatic from
      asymptomatic disc herniations.
AB  - Spinal canal dimensions are assumed to play a significant role with regard to the
      development of symptoms in individuals with disc herniations. The literature is
      inconclusive on the significance of spinal canal size as a risk factor for
      sciatica, mainly because of study design problems. The objective of this study,
      therefore, was to test the hypothesis that spinal canal dimensions are a
      significant risk factor for the development of sciatica, comparing symptomatic
      and asymptomatic individuals. Thirty symptomatic patients undergoing lumbar
      discectomy and 45 asymptomatic volunteers were investigated by clinical and MRI
      examination. The size of the spinal canal and thecal sac as well as the
      midsagittal spinal canal diameter were measured using a point counting method and
      scanner software, respectively. Differences between the groups were compared
      separately for each level L3/4 to L5/S1. The intra- and inter-observer error
      ranged between 0.95 and 0.99 for all measurements. In symptomatic patients, the
      dimensions of the spinal canal and thecal sac as well as the midsagittal spinal
      canal diameter were smaller at all disc levels. Unpaired t-test demonstrated a
      significant difference, ranging from P<0.05 to P<0.001. When controlled for age,
      sex and body height, the odds ratio for a symptomatic disc herniation increased
      to as high as 35, depending on the spinal level, when the size of the spinal
      canal was smaller than the mean for controls by two standard deviations or more.
      In symptomatic patients, spinal canal dimensions are significantly smaller than
      those in asymptomatic individuals. Spinal canal dimension is an important factor
      discriminating patients from control subjects. A clinically relevant grading
      system for disc herniation should therefore be based on the spatial relationship
      between herniated disc material and neurogenic structures.

PMID- 12522717
TI  - Psychosocial correlates of low-back pain in adolescents.
AB  - Knowledge is sparse concerning associations between juvenile low-back pain (LBP)
      and psychosocial factors. A cross-sectional study was performed to study whether
      juvenile LBP may be associated with self-reported headache and wellbeing, and
      with social class and parental LBP reported by the parents. The material
      comprised all adolescents (n=105), aged 14.1-16.1 years, in a rural municipality
      and in a nearby urban area in inland Norway. The response rate was 84% (n=88).
      Data were supplied from questionnaires filled out by the adolescents and their
      parents. Associations were calculated by bivariate and multivariate methods. The
      level of significance was set at P< or =0.05. In multivariate analyses,
      associations were found between LBP and both female gender and poor wellbeing, in
      particular poor self-perceived fitness. There was a tendency towards an
      association between weekly headache and LBP. No associations were found between
      social class, parental LBP and juvenile LBP. The results do not confirm
      hypotheses that social class and parental LBP are related to juvenile LBP. The
      findings indicate that poor wellbeing, in particular poor self-perceived fitness,
      is associated with LBP among adolescents.

PMID- 12522718
TI  - Pain and function after intradiscal electrothermal treatment (IDET) for
      symptomatic lumbar disc degeneration.
AB  - The goal of this study was to evaluate the short-term effects of intradiscal
      electrothermal treatment (IDET) for chronic discogenic low back pain. Twenty
      consecutive patients with symptomatic degenerative discs were treated with IDET
      and evaluated preoperatively, and 3 and 6 months postoperatively. Pain was
      measured with a 100-mm visual analog scale (VAS) and function was evaluated with
      the Oswestry score and SF-36 questionnaire. The VAS scores improved by 14 mm on
      average (P=0.046), but the individual scores show great variation. The Oswestry
      scores did not improve significantly. The SF-36 showed improvement, but only for
      the subscales vitality (P=0.023) and bodily pain (P=0.047). Based on these
      results, we conclude that IDET is not effective in reducing pain and improving
      functional performance in a sample of 20 patients treated for chronic discogenic
      low back pain after 6 months follow-up.

PMID- 12522719
TI  - Complications of pedicle screws in lumbar and lumbosacral fusions in 105
      consecutive primary operations.
AB  - Pedicle screw fixation is technically demanding and associated with high
      complication rates. The aim of this study was to identify and quantify the
      pedicle screw-related complications in 105 consecutive operations. We
      retrospectively analysed 105 consecutive primary operations. We found
      complications of varying severity in 54% of the patients. Deep infections were
      found in 4.7%, all successfully cured by debridement and antibiotics. There were
      no permanent neurological complications related to the screws. One serious
      neurological sequela, a T10 paraplegia, was unrelated to screw placement between
      L3 and S1. Screw misplacement was found in 6.5% of the screws. Screw breakage
      occurred in 12.4% of the patients, inevitably leading to loss of correction.
      Reduced spondylolisthesis L5-S1 without anterior support was found to be
      especially prone to screw breakage. The study confirmed that pedicle screw
      placement is a technically demanding procedure with a high complication rate.
      Fortunately, most complications are not severe. Infections can be dealt with by
      thorough debridement and parenteral antibiotics. Neurological sequelae can be
      minimised by careful tactile technique. To avoid screw breakage and subsequent
      loss of correction, anterior support should be provided, through either posterior
      or anterior lumbar interbody fusion (PLIF or ALIF) techniques, in reduced
      spondylolisthesis L5-S1.

PMID- 12522720
TI  - Excision of an osteoid osteoma from the body of the axis through an anterior
      approach.
AB  - Osteoid osteoma is seen less commonly in the vertebral body than in the posterior
      elements of the spine. To the authors' knowledge, this is only the second
      reported case of an osteoid osteoma affecting the body of the axis. The patient
      described in this report presented with the classic symptomatology of pain and
      torticollis. Radiological imaging confirmed the diagnosis. A superior extension
      of the anterior Smith-Robinson approach, through the "window of access" described
      by Fasel, was used to excise this lesion. Following surgical excision, there was
      complete resolution of the presenting symptomatology and functionally the range
      of motion of the cervical spine returned to normal. We avoided instrumentation
      and C1-C2 fusion so that rotation of the cervical spine could be maintained.
      There were no signs of recurrence of the tumour within the 4-year follow-up
      period. It presented in a classic way but, despite this, it took 2 years from the
      onset of these symptoms to reach a definitive diagnosis. This osteoid osteoma was
      successfully excised through a superior extension of the anterior Smith-Robinson
      approach.

PMID- 12522722
TI  - [Note to our readers].

PMID- 12522721
TI  - Traumatic bilateral locked facet at L4-5: report of a case associated with
      incorrect use of a three-point seatbelt.
AB  - We present a case of traumatic L4-5 bilateral facet dislocation, without
      neurological deficit, in a 32-year-old female patient, as an unusual seatbelt
      injury caused by positioning the shoulder harness improperly under her armpit.
      Open reduction, posterior interbody fusion, and posterior segmental
      instrumentation were carried out. The aim of this report is to describe this
      rarely encountered condition and speculate regarding automotive shoulder harness
      misuse as a potential cause of bilateral locked facet at L4-5, and to emphasize
      the importance of multidirectional X-ray on first examination. The unusual L4-5
      level facet interlocking was attributed to misuse of the automobile shoulder
      harness. We propose the importance of recognizing this injury and following up on
      such clues as transverse process fractures and/or widened posterior elements.

PMID- 12522723
TI  - [Area of competence of rescue services personnel].

PMID- 12522724
TI  - [The centennial of oxygen-therapy (1902 - 2002) -- reassessing its history. Part
      II: The contributions of the "Roth-Draeger anaesthesia apparatus" (1902) and
      other inventions of 100 years of Draeger-Medical-Technology (1902-2002) to the
      history of truly "therapeutic" application of oxygen].
AB  - This is the second part of a survey which analyses the history of inhalative
      oxygen therapy and its interactions with the history of anaesthesiology. Specific
      emphasis is put here on illustrating inventions of modern pressure gas technology
      such as pressure reducing valves. These enabled Draeger Inc. to be the first firm
      to develop and trade on a large scale technically convincing products allowing a
      rational, therapeutic application of oxygen. Especially Draeger anaesthesia
      apparatus (e. g. the "Roth-Draeger Anaesthesia Apparatus") and respiratory
      protective devices, which were available from 1902, proved also internationally
      successful from the very beginning. In the international historiography on
      inhalative oxygen therapy, however, these contributions have to our knowledge so
      far never been systematically considered. Consequently, J. S. Haldane (1860 -
      1936) is regarded there to have "founded" of modern oxygen therapy in 1917.
      Critically reviewing this earlier research, we propose a historical reassessment,
      concluding that the year 1902 was the historically decisive "turning point"
      towards the development of modern oxygen therapy.

PMID- 12522725
TI  - [Development of opioid tolerance -- molecular mechanisms and clinical
      consequences].
AB  - INTRODUCTION: One often identified effect of opioid administration is that of the
      development of tolerance to the analgesic effect. While it is generally agreed
      that tolerance to opioid analgesia does occur, it does not appear to be a
      limiting factor. Dose escalation in chronic pain therapy is considered to be
      predominantly a consequence of increasing pain, which is a result of increasing
      nociceptive input as the disease progresses. The underlying cause of tolerance to
      opioids, however, as commonly identified in the ICU can be identified as an
      adaptation process. When the opioid is given continuously several causes of
      adaptation can be identified, all of which can be traced back to the cellular and
      molecular level. RECEPTOR RELATED CHANGES INVOLVED IN TOLERANCE: Initial effects
      of opioid administration in most individuals are analgesia, sedation,
      nausea/vomiting, respiratory depression, pupillary constriction, constipation and
      euphoria or dysphoria. However, numerous studies and clinical experience suggest
      that tolerance to different opioid effects develop at different rates, which has
      been termed selective tolerance. While tolerance to nausea, vomiting, sedation,
      euphoria and respiratory depression occur rapidly, there is minimal development
      of tolerance to constipation and miosis. Such diversity suggest receptor-related
      differences in the speed of development of tolerance. In the ICU other compounds
      such as benzodiazepines, when given together with opioids, seem to speed up the
      rate of development of tolerance of the latter. Such an effect very likely is due
      to a reduction in activity of the descending inhibitory nervous system. In
      addition, there is surmountable data suggesting that the higher the intrinsic
      activity of the opioid at only one receptor site, lesser receptors are needed in
      order to induce a potent analgesic effect. As a net result the incidence of
      tolerance is less likely to become clinically apparent when potent ligands such
      as fentanyl or sufentanil are administered. N-METHYL-D-ASPARTATE (NMDA)
      ACTIVATION, OPIOID RECEPTOR INTERNALIZATION AND DESENSITIZATION: An altered
      metabolism has little effect on the rate of development of tolerance. In chronic
      pain treatment with morphine, however, an increased ratio of the metabolite
      morphine-3-glucuronide, with antiopioid effects, to morphine-6-glucuronide is
      associated with staggering doses of the analgesic. Opioids which interact with
      micro - and/or kappa-binding sites, demonstrate an adaptation process called
      desensitization which is due to a reduced interaction with the internal second
      messenger system called G-protein. This is only a short-lived phenomenon
      following binding of the ligand. Another underlying mechanism of tolerance
      development is that of internalization of the opioid receptors. This short-lived
      phenomenon, termed endocytosis, results in lesser binding sites available for the
      mediation of analgesia. Another and more relevant mechanism of long-term opioid
      binding is that of subsequent protein kinase C (PKC), phospholipase C (PLC)
      translocation and activation of nitric oxide synthetase (NOS). All of this
      contributes to a N-methyl-D-aspartate (NMDA) receptor activation with ensuing
      antiopioid effect and tolerance. CLINICAL CONSEQUENCES FOLLOWING THE DEVELOPMENT
      OF TOLERANCE: Most likely genetic difference in opioid receptor synthesis and
      difference in their affinities for various ligands is the cause for the wide
      margin of dose variability in patients (genetic polymorphism). Once tolerance to
      the analgesic effect of the opioid is observed and in order to avoid unnecessary
      further development of tolerance, simultaneous administration of other receptor
      mediated analgesics is advocated. In the perioperative period strategies like the
      multimodal analgesic concept is fostered. It consists of the simultaneous
      administration of low-dose ketamine, co-administration of an alpha 2-agonist, and
      the administration of a selective COX-2 inhibitor (refecoxib, parecoxib)
      respectively. In chronic pain therapy combined administration with either
      dextromethorpharphane, or opioid rotation of a more potent ligand such as
      methadone, fentanyl TTS or oxycodone is suggested. Since conversion factors are
      not reliable in opioid rotation, it is best to start off with 50 % of the
      equivalent dose and rapidly titrate to the desired effect. With regard to
      tolerance development in the ICU, co-administration of an alpha 2-agonist
      (clonidine, dexmedetomidine), and daily intermittent cessation of benzodiazepine
      administration are advocated. Since continuous dosing of an opioid, commonly
      handled in the ICU setting is more likely to induce tolerance, intermittent
      administration is advocated. Taken together, there is an abundance of
      experimental data which suggests, that with every dose of an opioid several
      adaptive processes are being initiated. Due to genetic polymorphism such
      adaptation is seen clinically with striking individual different dosages, the
      degree and the time of onset of tolerance. Although tolerance development may
      result in staggering doses of an opioid, there is no reason to evade the use of
      such agents. On the contrary, the concept of multimodal analgesia consisting of
      the simultaneous use of analgesics with a different mode of action can counteract
      tolerance development.

PMID- 12522726
TI  - [Initial medical treatment by paramedics in combined first aid operations of
      paramedics and emergency physicians].
AB  - OBJECTIVE: The present study was conducted to evaluate the quality of paramedic
      care and the feasibility and cost-effectiveness of sending a well-trained
      paramedic team to the sight of a medical emergency to initiate active medical
      treatment prior to the arrival of the mobile intensive care unit (MICU). METHODS:
      We examined 200 cases of medical treatment initiated by paramedics before arrival
      of the MICU team at the site of the medical emergency. Using a questionnaire, all
      emergency procedures performed by the paramedic team on scene were recorded and
      defined as "required", "carried out", and "accurately performed". The documented
      emergency procedures were divided into three categories: basic procedures (e. g.
      positioning, CRP, oxygen administration), additional procedures (e. g. placement
      of iv-lines, application of intravenous medication), and routine emergency
      diagnostic measures (e. g. monitoring of cardiopulmonary status). Further
      documented were the time of onset of emergency physician treatment, and the
      definitive transport vehicle used. To evaluate the time required for the measures
      performed, three different groups were identified according to the time gap
      between the arrival of the paramedic and the emergency physician teams (< 3 min,
      3 - 5 min and > 5 min). RESULTS: In the 200 emergencies included in the study, 76
      - 95 % of the required procedures were accurately performed prior to the arrival
      of the MICU team, at a success rate ranging from 87 to 100 %. CONCLUSIONS: In
      this study, a large number of emergency procedures could be performed by the
      paramedic team within a short period of time (in some cases < 3 min), and
      adequate effectiveness. Based on our results, the activation of paramedic-staffed
      first-tier ambulances with shorter response times is recommended in addition to
      the MICU system.

PMID- 12522727
TI  - [Current status of non-invasive ventilation in German ICU's -- a postal survey].
AB  - The status of non-invasive ventilation (NIV) in intensive care units (ICU) in
      Germany was analysed by a national survey. Questionnaires consisting of multiple
      choice and short-answer questions were sent to ICUs of university hospitals,
      hospitals with >1000 beds, with 500 - 1000 beds, and hospitals with <500 beds
      separated with regard to different specialties (anesthesia ICUs, surgical ICUs,
      cardiac surgical ICUs, neurosurgical ICUs, internal ICUs, interdiscipline ICUs).
      Of the 716 questionnaires sent 223 (32 %) were returned and analysed. The use of
      NIV in all specialties increased during the last 3 years. 14 % of ICUs in some
      specialties treated more than 30 % of patients with NIV. CPAP (88 %), BIPAP (45
      %) and ASB/PSV (48 %) were most frequently used as NIV-strategies. 10 % of all
      ICUs reported to have experience with proportional assist ventilation. NIV was
      most frequently used for disease states like COPD (82 %), pneumonia (64 %),
      pulmonary oedema (50 %), bronchial asthma (35 %) and ALI/ARDS (22 %). The use of
      NIV was considered when clinical signs of ventilation (93 %) and oxygenation
      [arterial blood gas analysis (92 %) and oxygen saturation (66 %)] were
      inadequate. Complications observed during NIV were panic reaction (83 %),
      ulceration of nose (38 %) and aspiration (14 %). The reasons to reject NIV were
      (total 13 %): lack of ventilators (64 %), expenditure of personnel (57 %) and
      risk of the procedure (11 %). 38 % of the ventilators used were older than 5
      years. 56 % of the ICUs were content with the equipment for NIV. 76 % of the ICUs
      were interested to buy new equipment of NIV. 99 % of the survey have declined NIV
      as an alternative method of ventilation. In summary we found NIV as an accepted
      additional method of ventilatory support in respiratory failure in German ICUs.
      We found no significant increase in frequency of NIV in the last three years.

PMID- 12522728
TI  - [Aprotinin -- an allogeneic transfusion sparing drug].

PMID- 12522729
TI  - [Safety of autologous blood donation before cardial surgery].

PMID- 12522730
TI  - [BSE, prions, vCJD and (not only) homologous transfusion].

PMID- 12522731
TI  - [Artificial oxygen carriers -- a critical analysis of current developments].

PMID- 12522732
TI  - Autologous transfusion -- a reasonable measure under the principles of health
      economics?

PMID- 12522733
TI  - [Rupture of the trachea after emergency endotracheal intubation].
AB  - The rupture of the trachea is a rare but serious complication after endotracheal
      intubation. We report the case of a 77-year-old severely diseased woman with
      emergency intubation after development of acute respiratory distress. Four days
      after the emergency intubation a laceration of the membraneous part of the
      trachea was diagnosed. The patients general condition and the infaust prognosis
      resulted in the lack of therapeutic options and the death of the patient.
      According to the forensic autopsy the secondary perforation is probably a
      consequence of intubation or a pressure lesion of the tube in combination with a
      weakness of the membraneous part of the trachea due to impaired microperfusion.
      Every physician performing an intubation has to be aware of the risk and the
      consequences of a tracheal rupture.

PMID- 12522734
TI  - [Editorial -- topics from other journals].

PMID- 12522735
TI  - [Emergency medicine -- new concepts and therapies improve outcome from cardiac
      arrest].
AB  - According to scientific articles focusing on emergency medicine published in
      international journals in the past few months, early defibrillation by lay
      persons, thrombolysis during cardiopulmonary resuscitation (CPR) and treatment
      with mild therapeutic hypothermia have been identified as relevant, new and
      clinically important treatment options to improve outcome following cardiac
      arrest. Early defibrillation using automated external defibrillators by lay
      persons reduces the time interval between collapse and first attempts at
      defibrillation and thus improves outcome after prehospital cardiac arrest.
      Thrombolysis during CPR -- for which the results regarding safety and efficacy
      are available from nonrandomized trials -- can also be safely performed in case
      of pulseless electrical activity. Thrombolysis during cardiopulmonary
      resuscitation has, however, no significant effect in this subgroup of patients
      with pulseless electrical activity in whom outcome is poor if the drug is
      administered at the end of conventional CPR procedures. Mild therapeutic
      hypothermia, i. e., cooling of cardiac arrest victims to 32-34 degrees C central
      body temperature for 12-24 h following out-of-hospital cardiac arrest, markedly
      improves survival rate and neurological outcome. Since this has now been clearly
      documented in two randomized clinical trials, it can be assumed that this kind of
      intervention will be recommended and translated into clinical practice soon. In
      conclusion, new and clinically relevant methods to improve outcome following
      cardiac arrest are available and can now be widely used clinically.

PMID- 12522736
TI  - The essence of spirituality of terminally ill patients.
AB  - The purpose of this hermeneutic study was to investigate the essence of
      spirituality of terminally ill patients. In-depth unstructured interviews were
      used as the method for data collection. In the six-month period of data
      collection, the researcher was in the role of a hospice palliative care
      consultant who directly took care of the subject patients in a hospice ward of a
      teaching hospital. The six subjects were selected purposively according to
      various demographic backgrounds. Interview transcripts provided the data for
      analysis. The results were composed of four constitutive patterns and ten themes.
      The first constitutive pattern was "Communion with Self" which included three
      themes: (1) Self-identity--spirituality is the discovery of the authentic self.
      (2) Wholeness--a human being is full of contradictions but still in wholeness.
      (3) Inner peace--spirituality is negotiating conflicts for self-reconciliation.
      The second constitutive pattern was "Communion with others" which included two
      themes: (1) Love--spirituality is a caring relationship but not an over
      attachment to others. (2) Reconciliation--spirituality is to forgive and to be
      forgiven. The third constitutive pattern was "Communion with Nature" which
      included two themes: (1) Inspiration from the nature--spirituality is the
      resonance of the marvelous beauty of nature. (2) Creativity--spirituality is
      conceiving imaginatively. The fourth constitutive pattern was "Communion with
      Higher Being" which included three themes: (1) Faithfulness--spirituality is
      keeping the trust dependably. (2) Hope--spirituality is claiming possibilities.
      (3) Gratitude--spirituality is giving thanks and embracing grace. The scientific
      rigor of this qualitative research as well as the strength and limitations of the
      study are reported. Implications for hospice palliative care and future research
      are recommended.

PMID- 12522737
TI  - Endemic hepatitis C virus infection in a seaboard village of southwestern Taiwan.
AB  - This study investigated the rate of Hepatitis C Virus (HCV) infection and
      identified the risk factors associated with a HCV infection at Ma-Sha-Gou, a
      seaboard village in southwestern Taiwan. In total, 240 subjects were sampled and
      stratified according to age and sex from 1,200 residents aged 20-64 years old.
      HCV-specific antibodies (anti-HCV Ab) in blood specimens were tested for HCV
      seropositive by the third-generation HCV ELISA system. The subjects, later
      identified as 152 seropositive and 88 seronegative, were selected for analysis of
      the correlates of HCV infection. They were interviewed to explore a variety of
      possible risk factors for HCV infection with a structured questionnaire. The
      results showed that the anti-HCV age-adjusted seroprevalence was 55.8%. Needle
      injection was significant to the increased anti-HCV seroprevalence, with
      multivariate age-adjusted odds ratio (OR) and confidence interval (CI) of 1.9 and
      1.2-3.9 respectively. This study identifies Ma-Sha-Gou as an endemic area of HCV
      infection, in which needle injection from any medical activity was a possible
      transmission pathway in the village, and suggests the health
      authorities/community health nurses should give the residents a comprehensive
      community-based education program to interrupt HCV transmission.

PMID- 12522738
TI  - Perceived occupational stress and related factors in public health nurses.
AB  - The purposes of this study were to explore perceived occupational stress and
      related factors in public health nurses (PHNs). A convenient sampling method was
      used to recruit the subjects. Seven out of 12 district health centers in Taipei
      City and all 11 district health centers in Kaohsiung City agreed to participate
      in this study. Of the 171 PHNs invited to participate, 167 (97.7%) completed all
      mailing questionnaires. Findings showed that (1) the major sources of
      occupational stress in PHNs were personal responsibility and workloads, and (2)
      PHNs with younger age, shorter length of current working experience, longer past
      clinical experience, higher level of education, and less pre-job or on-job
      continuous education perceived more occupational stress. The findings indicate
      that it is necessary to develop stress-alleviating programs to reduce
      occupational stress in PHNs. Designing a systematic in-service training program
      to enhance working competency and performance of PHNs is also suggested.

PMID- 12522739
TI  - The effectiveness of health promotion education programs for community elderly.
AB  - The purpose of this study was to examine the effectiveness of health promotion
      education programs for a group of elderly residents in a community. A one group
      pre- and post-test design was used in this study. Nurses, dietitians, and
      physical education teachers worked collaboratively to provide a series of
      comprehensive, integrated education programs. Course content included healthy
      life style and health promotion, disease prevention, nutrition, exercise, and
      medication education. A total of 140 elderly participated in this study. Ninety-
      seven subjects attended all of the education programs. A structured questionnaire
      was used for data collection. Information about demographics, health status,
      health promotion knowledge and behaviors was included. The health promotion
      behavior data were collected twice. The initial data set was collected prior to
      the first course and the second after the fifth course. Health promotion
      knowledge was assessed pre- and post-test in the second, third, and fourth
      courses. The research findings revealed that the education programs were
      effective in improving elderly health promotion knowledge and behaviors. The
      scores for health promotion knowledge and positive health behaviors were high
      among subjects who were aged 65-69 years, were married, lived with family members
      and had higher education levels. The results could be used as a reference in
      future health promotion education in the community.

PMID- 12522740
TI  - Effects of perceived self-efficacy and functional status on depression in
      patients with chronic heart failure.
AB  - The purpose of this study was to test the relationships between perceived self
      efficacy, functional status and depression in a group of chronic heart failure
      patients. The conceptual model for this study was primarily derived from
      Bandura's social learning theory. The study is based on an exploratory,
      correlational design. A sample of 100 chronic heart failure patients who met the
      inclusion criteria were recruited from four cardiovascular clinics of major
      hospitals in northern Taiwan. The instruments used in this study included
      Jenkins' Self-Efficacy Expectation Scales, Seattle Angina Inventory, and
      Geriatric Depression Scale. Results demonstrate a significant inverse
      relationship between perceived self-efficacy and depressive symptoms (r = -.61, p
      < .001), a significant positive relationship between perceived self-efficacy and
      functional status (r = .55, p < .001), and a significant negative relationship
      between functional status and depressive symptoms (r = -.33, p < .001). The
      findings of the path analysis support the hypothesis that after controlling for
      disease severity, perceived self-efficacy has a direct and negative effect on
      depressive symptoms. An indirect effect of perceived self-efficacy on depression
      through functional status in heart failure patients was also revealed in the
      finding. All paths in the model were significant (p < .05). Results of the study
      can help to identify heart failure patients who are at risk for low perceived
      self-efficacy, low functional status, and a depressed mood. Nursing intervention
      to address these factors can then be developed and tested.

PMID- 12522741
TI  - Nurses' experience of caring for delirious patients.
AB  - This qualitative research was aimed at understanding nurses' experiences of
      caring for delirious patients. Four in-depth open-ended interviews were analyzed.
      A model to present the caring experience was developed from the interviews. The
      experience of caring for the delirious patient is a process of "striving for
      balance". Informants reported trying to deal with unanticipated patient
      conditions and the unyielding workloads by balancing these two conditions. Some
      of the actions pursued included: relying on outer resources, assuring safety,
      reporting, and supporting each other. Understanding the nurses' caring experience
      is important for the nurse administrators in helping the nurse manage delirious
      patients. Suggestions for future research are also made.

PMID- 12522742
TI  - Evaluations of emotional reactions and coping behaviors as well as correlated
      factors for infertile couples receiving assisted reproductive technologies.
AB  - The purpose of this research was to explore the following objectives for
      infertile couples receiving infertility treatment: Differences between wives and
      husbands in their emotional reactions and coping behaviors. This research, using
      structured questionnaires, was based on 120 infertile couples attending the
      Intrauterine Insemination (IUI) or the In Vitro Fertilization-Embryo Transfer
      (IVF-ET) program. The research instruments consisted of Demographic Data Form,
      Profile of Mood States (POMS), and Ways of Coping Questionnaire. The research
      results showed that infertile wives experienced more emotional disturbance than
      husbands did, as shown in the four subscales of Tension-Anxiety, Depression
      Dejection, Anger-Hostility, and Fatigue-Inertia, as well as the total scale of
      POMS. It was also shown that wives adopted more coping behaviors to deal with
      infertility and treatment than husbands did, as revealed in the subscales of Self
      Controlling, Seeking Social Support and Escape-Avoidance and the total scale of
      the Ways of Coping Questionnaire. All of the above reached significant
      statistical differences. The emotional reactions of infertile couples varied with
      the differences in education levels, duration of treatment, number of treatments
      received, and numbers of existing children. The emotional reactions of infertile
      husbands had a significantly positive correlation with the factors Confronting,
      Accepting Responsibility, and Escape-Avoidance. The emotional reactions of wives
      had a significantly negative correlation with Positive Reappraisal. The research
      results can provide clinical staff with a correct understanding of the
      differences between husbands and wives in emotional reactions and coping
      behavior, as well as related factors, to help them to provide better medical
      treatment.

PMID- 12522743
TI  - Impact of a transtheoretical model on the psychosocial factors affecting exercise
      among workers.
AB  - The purpose of this study was to investigate the effects of exercise intervention
      on improvement of perceived exercise benefit, perceived exercise barrier, and
      exercise self-efficacy. A quasi- experimental design was utilized and purposive
      sampling was conducted at a telecom worksite in southern Taiwan. One hundred and
      ninety-three subjects were assigned to an experimental and a control group. The
      experimental group, which consisted of 133 subjects, participated in a program of
      exercise intervention. The intervention program applied a transtheoretical model
      to aid subjects in developing effective approaches within different stages of the
      exercise change. It included written materials and teaching activities for the
      different stages of exercise. The control group, which consisted of 60 subjects,
      had no treatment. All subjects completed a structured questionnaire, including
      perceived exercise benefits, perceived exercise barriers, exercise self-efficacy,
      and stages of exercise, pre-test and post-test. Statistical analyses included Chi
      square test, paired t-test, analysis of covariance, one-way ANOVA, and Scheffe's
      post hoc comparison. After the exercise intervention, the results post-test of
      the experimental group showed that (1) perceived exercise benefit, perceived
      exercise barriers, and exercise self-efficacy improved significantly, and (2)
      perceived exercise benefit and exercise self-efficacy were significantly higher
      than those of the control group post-test while perceived exercise barriers were
      significantly lower than those of the control group post-test.

PMID- 12522744
TI  - Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis
      of prevalence and risk factors.
AB  - Reports suggest that carriage of methicillin-resistant Staphylococcus aureus
      (MRSA) among persons without health care-associated risks has increased. A meta
      analysis of studies reporting the prevalence of community-acquired MRSA (CA-MRSA)
      among MRSA isolates from hospitalized patients or the prevalence of MRSA
      colonization among community members was conducted. The CA-MRSA prevalence among
      hospital MRSA was 30.2% in 27 retrospective studies and 37.3% in 5 prospective
      studies; 85% of all patients with CA-MRSA had > or =1 health care-associated
      risk. The pooled MRSA colonization rate among community members was 1.3% (95%
      confidence interval [CI], 1.04%-1.53%), but there was significant heterogeneity
      among study populations. Community members from whom samples were obtained in
      health care facilities were more likely to be carrying MRSA than were community
      members from whom samples were obtained outside of the health care setting
      (relative risk, 2.35; 95% CI, 1.56-3.53). Among studies that excluded persons
      with health care contacts, the MRSA prevalence was 0.2%. Moreover, most persons
      with CA-MRSA had > or =1 health care-associated risk, which suggests that the
      prevalence of MRSA among persons without risks remains low (< or =0.24%).
      Effective control of dissemination of MRSA throughout the community likely will
      require effective control of nosocomial MRSA transmission.

PMID- 12522745
TI  - Spectrum of bacille Calmette-Guerin (BCG) infection after intravesical BCG
      immunotherapy.
AB  - Intravesical instillation of bacille Calmette-Guerin (BCG) effectively treats
      transitional cell carcinoma of the bladder. Occasionally, BCG infection
      complicates such treatment. In some patients, infection appears early (within 3
      months after instillation) and is characterized by generalized symptoms, with
      pneumonitis and hepatitis. Late-presentation disease occurs >1 year after the
      first BCG treatment and usually involves focal infection of the genitourinary
      tract (the site at which bacteria were introduced) and/or other sites that are
      typical for reactivation of mycobacterial disease, such as the vertebral spine or
      the retroperitoneal tissues. Noncaseating granulomas are found in the majority of
      cases, whether early or late. Most patients respond to treatment with
      antituberculous drugs; in early-presentation disease, when features of
      hypersensitivity predominate, glucocorticosteroids are sometimes added. Late
      localized infection often requires surgical resection.

PMID- 12522746
TI  - Epidemiology and risk factors for gram-positive coccal infections in neutropenia:
      toward a more targeted antibiotic strategy.
AB  - The objective of this study was to evaluate the risk of acquiring gram-positive
      coccal infections in febrile neutropenic patients and to develop risk indexes for
      gram-positive and streptococcal infections. This prospective, multicenter study
      included 513 patients. The prevalence of gram-positive coccal infections was 21%
      (14% were staphylococcal infections and 7.8% were streptococcal infections). The
      mortality rate during the month after study enrollment was 5%. On multivariate
      analysis, the occurrence of gram-positive coccal infections was significantly
      associated with receipt of high-dose cytarabine therapy, proton pump inhibitors,
      and gut decontamination with colimycin without glycopeptides and presence of
      chills. Staphylococcal infection was significantly associated with use of
      nonabsorbable colimycin, and streptococcal infection was associated with
      diarrhea, use of nonabsorbable antifungals, receipt of high-dose cytarabine, and
      gut decontamination with colimycin. The relative risks for streptococcal
      infection were 2.9, 13.2, and 20.7 in the presence of 1, 2, and > or =3
      parameters, respectively. Risk factors for staphylococcal and streptococcal
      infections differ among neutropenic patients. A simple scoring system for
      predicting streptococcal infection is proposed.

PMID- 12522747
TI  - Linezolid for the treatment of multidrug-resistant, gram-positive infections:
      experience from a compassionate-use program.
AB  - Linezolid was provided for treatment of multidrug-resistant, gram-positive
      infections through a compassionate-use program. Patients (n=796) received 600 mg
      of linezolid intravenously or orally every 12 h (828 treatment courses).
      Bacteremia was present in 46% of infections, endocarditis was present in 10.6%,
      and line-related infections were present in 31.1%. Other infections included
      intraabdominal infections (15.1%), complicated skin and skin-structure infections
      (13.3%), and osteomyelitis (10.7%). Causative pathogens included vancomycin
      resistant enterococci (66.3%) and methicillin-resistant staphylococci (22.1%).
      Clinical intent-to-treat (ITT) outcomes in the evaluable population were as
      follows: cure, 73.3%; failure, 6.8%; and indeterminate, 19.9%. Microbiological
      ITT outcomes in evaluable patients were as follows: cure, 82.4%; failure, 14.1%;
      and indeterminate, 3.5%. At the test of cure assessment, the clinical cure and
      microbiological success rates were 91.5% and 85.8%, respectively. The most common
      adverse events possibly related to linezolid use were gastrointestinal
      disturbances (9.8% of cases), thrombocytopenia (7.4% of cases), decreased
      hemoglobin/hematocrit levels (4.1% of cases), and cutaneous reactions (4.0% of
      cases). Linezolid provided high rates of clinical cure and microbiological
      success in this complicated patient population, with very good overall tolerance.

PMID- 12522748
TI  - Recognizing influenza in older patients with chronic obstructive pulmonary
      disease who have received influenza vaccine.
AB  - A substudy analysis was conducted to determine the clinical characteristics
      associated with symptomatic, laboratory-documented influenza (LDI) among 2215
      veterans with chronic obstructive pulmonary disease who participated in
      Department of Veterans Affairs Cooperative Study 448 and who received trivalent
      inactivated influenza virus vaccine with or without intranasal live-attenuated,
      cold-adapted influenza vaccine. Of 585 evaluable first occurrences of acute
      respiratory illnesses, 94 (16%) were LDI. Respiratory symptoms of cough, sputum
      production, and dyspnea occurred in >90% of patients with LDI; 68% had documented
      or subjective fever, and 81% had myalgias. Stepwise logistic regression
      identified only fever and myalgia as being statistically associated with LDI.
      During the influenza outbreak period, the positive predictive value of fever and
      myalgia was 41%. Clinical criteria were poor predictors of LDI in these older,
      vaccinated patients with chronic lung disease. Additional studies are warranted
      to define optimal methods for the diagnosis of influenza among older persons with
      chronic obstructive pulmonary disease.

PMID- 12522749
TI  - Tonsillopharyngitis caused by foodborne group A streptococcus: a prison-based
      outbreak.
AB  - An outbreak of tonsillopharyngitis due to Streptococcus pyogenes occurred among
      inmates of a rural correctional center in New South Wales, Australia. A total of
      72 (28%) of 256 inmates became ill in December 1999. S. pyogenes type M-75, T-25,
      which was opacity factor positive, was isolated from throat swab specimens
      obtained from 5 of 57 inmates with primary cases and from 4 of 15 inmates with
      secondary cases, as well as from specimens obtained from the hand wounds and
      throat of one of the food handlers. The consumption of curried egg rolls (i.e.,
      curried egg salad sandwiches) was the most likely association with this outbreak.
      The presumed source of the food contamination was the food handler who had
      infected hand wounds. There has been only one other outbreak of streptococcal
      pharyngitis reported from a prison. Other outbreaks have been reported from
      military bases, nursing homes, and community picnics.

PMID- 12522750
TI  - Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to
      fluoroquinolones and nitrofurantoin.
AB  - In vitro surveillance data from across the United States indicate that
      approximately 10%-20% of urinary Escherichia coli isolates from female
      outpatients are resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Alternative
      therapies for uncomplicated urinary tract infections in women include
      fluoroquinolones and nitrofurantoin, but the activities of these agents against
      TMP-SMX-resistant isolates are rarely reported. Among TMP-SMX-resistant urinary
      E. coli isolates tested in US laboratories from 1998 through 2001, 9.5% (5767 of
      60,414) were resistant to ciprofloxacin and 1.9% (1214 of 63,817) were resistant
      to nitrofurantoin; 10.4% of ciprofloxacin-resistant isolates (683 of 6560) were
      resistant to nitrofurantoin. An association between resistance to
      fluoroquinolones and nitrofurantoin in E. coli has not been previously reported
      and warrants further study.

PMID- 12522751
TI  - Indications for the immunological evaluation of patients with meningitis.
AB  - Although people with bacterial meningitis lack adequate protective antibody
      against the invading pathogen, most do not have an underlying immunodeficiency.
      Certain comorbid conditions increase the risk for development of bacterial sepsis
      and meningitis. In addition, certain congenital complement deficiencies, defects
      of antibody production, or asplenia may be first recognized by the occurrence of
      bacterial meningitis, particularly when it occurs in infants or young children.
      Deficiencies of the terminal components of complement (C5-C9) or properdin have
      been associated with recurrent or invasive neisserial infections, and asplenia,
      agammaglobulinemia, and deficiencies of the early components of complement (e.g.,
      C1-C3) are associated with risks of infections caused by Streptococcus
      pneumoniae, Haemophilus influenzae, and meningococci. The presence of congenital
      or acquired immunodeficiencies should be considered in persons who present with
      bacterial meningitis on the basis of the etiology, clinical epidemiology, and
      presence of other risk factors.

PMID- 12522752
TI  - Assisted reproductive technology for men and women infected with human
      immunodeficiency virus type 1.
AB  - In 2001, the World Health Organization reported 4.3 million new human
      immunodeficiency virus (HIV) infections in adults globally, 41% of which were in
      women. During the year 2000, 27% of newly diagnosed HIV infections in the United
      States occurred in women. In developed countries, the perception of HIV infection
      has changed from an acute, lethal infection to a chronic illness; the
      introduction of highly active antiretroviral therapy has decreased morbidity and
      mortality, and new drug therapies have dramatically decreased perinatal
      transmission. In view of these advances, some HIV-infected individuals are
      considering reproduction. Following the lead of organizations in other developed
      countries, the American College of Obstetricians and Gynecologists has recently
      endorsed the use of reproductive technology in HIV-infected patients. Which
      patients should be offered assisted reproduction and what the optimal methods are
      of decreasing heterosexual and perinatal HIV transmission must be determined.

PMID- 12522753
TI  - Scientific and ethical considerations in trial design for investigational agents
      for the treatment of human immunodeficiency virus infection.
AB  - The design of clinical trials for new antiretroviral agents poses unique
      challenges, given the availability of highly active antiretroviral therapy
      (HAART). These challenges include the selection of appropriate populations, the
      methods used to partition the effects of the study drug under observation from
      those of the other concurrently administered medications in early studies,
      performance of dose-ranging studies for disease states in which suboptimal drug
      exposure may lead to the development of viral resistance that limits future
      treatment options, and the need to fulfill the obligations of international
      regulatory agencies. Throughout, science and ethics are tightly woven elements in
      study designs for antiretroviral drug trials. Fast-track drug approval status and
      successful lobbying by advocates for patients with acquired immunodeficiency
      syndrome aimed at the US Food and Drug Administration, the National Institutes of
      Health, the Centers for Disease Control and Prevention, university teaching
      centers, pharmaceutical companies, and members of Congress undoubtedly
      contributed to the development and swift regulatory approvals of the 17
      antiretroviral medications now available in the United States for the treatment
      of human immunodeficiency virus infection.

PMID- 12522754
TI  - A prospective study of genital herpes simplex virus type 2 infection in human
      immunodeficiency virus type 1 (HIV-1)-seropositive women: correlations with CD4
      cell count and plasma HIV-1 RNA level.
AB  - A cohort of 217 human immunodeficiency virus type 1 (HIV-1)-seropositive women
      was observed prospectively from 1996 through 2000 to determine the frequency of
      genital herpes simplex virus type 2 (HSV-2) disease (symptomatic and
      asymptomatic) and to correlate those findings with HIV-1-related
      immunosuppression (absolute CD4 cell counts and plasma HIV-1 RNA levels).
      Participants underwent twice-yearly pelvic examinations, including cultures of
      cervicovaginal specimens and swab specimens from genital lesions, if lesions were
      present. Of the participants, 72 (33%) had genital HSV-2 infection diagnosed on
      the basis of either history alone (23 [32%]) or positive culture results (49
      [68%]). The 72 women who had genital herpes diagnosed completed 242 total visits.
      Of these visits, positive HSV-2 culture results were noted at 80 (33%); at 23
      (29%) of the 80 visits at which there were HSV-2-positive cultures, culture
      results were not associated with a clinically apparent genital lesion. Positive
      HSV-2 culture results occurred more frequently for samples obtained from patients
      with higher plasma HIV-1 RNA levels (P=.019) and lower CD4 cell counts (P<.001).

PMID- 12522755
TI  - Greater effect of highly active antiretroviral therapy on survival in people aged
      > or =50 years compared with younger people in an urban observational cohort.
AB  - Although human immunodeficiency virus-infected people aged > or =50 years have a
      blunted CD4 cell recovery when receiving highly active antiretroviral therapy
      (HAART), there are few data on mortality. Mortality rates were studied for 253
      individuals aged > or =50 years and a younger group of 535 people in a
      retrospective cohort; for untreated persons in each age group, the proportions
      surviving at 3 years were 83% and 70% (P<.01), respectively. No significant
      difference in the survival rate was found between the older (83%) and younger
      (89%) patients who received HAART (P=.29). The hazard ratio for death in the
      older untreated group was 2.4 (95% confidence interval [CI], 1.4-3.9) when
      exposed to HAART. However, compared with older untreated patients, the hazard
      ratio for death decreased to 0.28 (95% CI, 0.15-0.52) for treated older adults.
      The effect of HAART substantially improves the survival rate for older
      individuals and supports the importance of treatment in this group.

PMID- 12522756
TI  - Geographical differences in human oral yeast flora.
AB  - The oral yeast flora of healthy humans from eastern North America and China were
      sampled and compared. Chinese persons harbored a greater number and diversity of
      yeast species in the mouth. Furthermore, Candida albicans, which is the
      predominant commensal and etiologic species of candidiasis in Europe and the
      Western Hemisphere, was relatively rare in China.

PMID- 12522757
TI  - Pneumonitis associated with Ureaplasma urealyticum in children with cancer.
AB  - We describe 3 pediatric patients with cancer who had clinical and radiographic
      evidence of pneumonitis and for whom cultures of bronchoalveolar lavage fluid
      specimens yielded Ureaplasma urealyticum. Two of the patients died; for the
      surviving patient, clinical improvement coincided temporally with administration
      of erythromycin. Immunocompromised patients with pneumonitis of unclear etiology
      should have respiratory secretions cultured for mycoplasmas and should receive
      empiric therapy that includes a macrolide antibiotic.

PMID- 12522758
TI  - Severe prolonged red blood cell aplasia and thrombocytopenia induced by
      parvovirus B19 infection in a patient with sarcoidosis.
AB  - We describe an acromegalic patient who developed a parvovirus B19 (PVB19)
      infection concomitantly with sarcoidosis, which was complicated by chronic red
      blood cell aplasia and severe thrombocytopenia, despite disappearance of the
      virus from serum and the production of high levels of specific polyclonal
      antibodies to PVB19. Mitogen stimulation of the patient's peripheral blood
      mononuclear cells induced oversecretion of interferon-gamma (IFN-gamma). Because
      hematopoietic suppression by IFN-gamma has been reported, a possible mechanism
      underlying reticulocytopenia and thrombocytopenia could involve IFN-gamma.

PMID- 12522759
TI  - Medical and social analysis of prisoners with tuberculosis in a Russian prison
      colony: an observational study.

PMID- 12522760
TI  - Choosing an optimal strategy to assess and treat adults with pharyngitis.

PMID- 12522761
TI  - Linezolid versus vancomycin for methicillin-resistant Staphylococcus aureus
      infections.

PMID- 12522762
TI  - Candida lusitaniae infections in the era of fluconazole availability.
AB  - Amphotericin B resistance among isolates of Candida lusitaniae has distinguished
      it among Candida species. Because no comprehensive review has been published
      recently, we provide a case report and a literature review of C. lusitaniae
      infection to update and better characterize the illness in the era of azole
      availability and standardized methodologies for antifungal susceptibility
      testing. C. lusitaniae infection in the 55 cases surveyed in this review occurred
      in relatively young patients (median age, 44 years). Fungemia was found in 80% of
      patients. Other infection syndromes, including peritonitis, meningitis, and
      urinary tract infection, were much less common. Three-fourths of the patients had
      serious underlying medical conditions. Despite the presence of fungemia and
      predisposing comorbidities, death due to C. lusitaniae infection was uncommon
      among treated patients (5.00%). Moreover, in vitro susceptibility testing results
      for amphotericin B did not appear to predict patient outcome in this survey.

PMID- 12522763
TI  - Macrolide-resistant pneumococcal endocarditis and epidural abscess that develop
      during erythromycin therapy.
AB  - Suppurative complications of Streptococcus pneumoniae infections have become
      uncommon in the antibiotic era. We report a case of pneumococcal bacteremia and
      pneumonia complicated with epidural abscess and endocarditis in which macrolide
      resistance (the MLS(B) phenotype) emerged during erythromycin therapy. Genetic
      determinants known to mediate the most common mechanisms of macrolide resistance
      (methylation of the 23S rRNA and antibiotic efflux) were not detected by
      polymerase chain reaction or DNA hybridization. Sequence analysis of the DNA
      encoding the 23S rRNA of the macrolide-resistant isolate from the patient
      demonstrated the replacement of adenine by thymine at position 2058 (A2058T) in 2
      of 4 alleles. Clinicians should be alert to the possibility of the emergence of
      resistance during macrolide therapy for community-acquired pneumonia,
      particularly if suppurative complications of pneumococcal infection are
      suspected.

PMID- 12522764
TI  - Asymptomatic nasal carriage of mupirocin-resistant, methicillin-resistant
      Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in
      household contacts.
AB  - Recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection in a
      patient with diabetes and in his wife is described. Culture of nares samples from
      the family dog grew mupirocin-resistant (minimum inhibitory concentration >1024
      microg/mL) MRSA that had a pulsed-field gel electrophoresis chromosomal pattern
      identical to the MRSA isolated from the patient's nares and his wife's wound.
      Further recurrence of MRSA infection and nasal colonization in the couple was
      prevented only after successful eradication of MRSA from the family dog's nares.

PMID- 12522766
TI  - Cerebellar brain abscess associated with tongue piercing.
AB  - We describe a previously healthy adult who had a solitary cerebellar brain
      abscess diagnosed. This infection occurred 4 weeks after the patient underwent a
      tongue piercing procedure that was complicated by an apparent local infection.
      The clinical history, abscess culture results, and lack of an alternative
      explanation suggest that infection of the tongue piercing site was the source of
      the cerebellar abscess.

PMID- 12522765
TI  - Postmalaria neurological syndrome: two cases from the Gambia.
AB  - We describe 2 patients with severe Plasmodium falciparum malaria whose
      convalescence was complicated by fever, with acute confusion and acalculia in one
      patient and a triad of myoclonus, tremor, and dysphasia in the other.
      Inflammatory changes were found in cerebrospinal fluid samples. Postmalaria
      neurological syndrome was diagnosed in each patient, and a therapeutic response
      to oral corticosteroids was seen in the second patient.

PMID- 12522767
TI  - Mice lacking ZFHX1B, the gene that codes for Smad-interacting protein-1, reveal a
      role for multiple neural crest cell defects in the etiology of Hirschsprung
      disease-mental retardation syndrome.
AB  - Recently, mutations in ZFHX1B, the gene that encodes Smad-interacting protein-1
      (SIP1), were found to be implicated in the etiology of a dominant form of
      Hirschsprung disease-mental retardation syndrome in humans. To clarify the
      molecular mechanisms underlying the clinical features of SIP1 deficiency, we
      generated mice that bear a mutation comparable to those found in several human
      patients. Here, we show that Zfhx1b-knockout mice do not develop postotic vagal
      neural crest cells, the precursors of the enteric nervous system that is affected
      in patients with Hirschsprung disease, and they display a delamination arrest of
      cranial neural crest cells, which form the skeletomuscular elements of the
      vertebrate head. This suggests that Sip1 is essential for the development of
      vagal neural crest precursors and the migratory behavior of cranial neural crest
      in the mouse. Furthermore, we show that Sip1 is involved in the specification of
      neuroepithelium.

PMID- 12522768
TI  - Identification of PEX7 as the second gene involved in Refsum disease.
AB  - Patients affected with Refsum disease (RD) have elevated levels of phytanic acid
      due to a deficiency of the peroxisomal enzyme phytanoyl-CoA hydroxylase (PhyH).
      In most patients with RD, disease-causing mutations in the PHYH gene have been
      identified, but, in a subset, no mutations could be found, indicating that the
      condition is genetically heterogeneous. Linkage analysis of a few patients
      diagnosed with RD, but without mutations in PHYH, suggested a second locus on
      chromosome 6q22-24. This region includes the PEX7 gene, which codes for the
      peroxin 7 receptor protein required for peroxisomal import of proteins containing
      a peroxisomal targeting signal type 2. Mutations in PEX7 normally cause
      rhizomelic chondrodysplasia punctata type 1, a severe peroxisomal disorder.
      Biochemical analyses of the patients with RD revealed defects not only in
      phytanic acid alpha-oxidation but also in plasmalogen synthesis and peroxisomal
      thiolase. Furthermore, we identified mutations in the PEX7 gene. Our data show
      that mutations in the PEX7 gene may result in a broad clinical spectrum ranging
      from severe rhizomelic chondrodysplasia punctata to relatively mild RD and that
      clinical diagnosis of conditions involving retinitis pigmentosa, ataxia, and
      polyneuropathy may require a full screen of peroxisomal functions.

PMID- 12522769
TI  - Proceedings of a consensus conference: blood-borne HIV and hepatitis-optimizing
      the donor selection process.
AB  - Over the past several years, concern for the safety of blood transfusion has
      evolved from a primary focus on bacterial infections such as syphilis to viral
      infections including hepatitis B, C, and human immunodeficiency virus (HIV), and
      most recently, the theoretical risk of variant Creutzfeldt-Jakob Disease (vCJD).
      As a result of these changes, blood bankers have found themselves faced with the
      dilemma of balancing the rights of transfusion recipients to receive safe blood
      products, with the rights of individuals wishing to donate blood as an altruistic
      contribution to society.

PMID- 12522770
TI  - Prenatal typing of Rh and Kell blood group system antigens: the edge of a
      watershed.
AB  - Knowledge of the molecular basis of the blood group systems has enabled the
      development of assays for blood group genotyping. At this time, polymerase chain
      reaction (PCR)-based assays validated on fetal material obtained by invasive
      means (chorionic villus sampling or amniocentesis) are available for all
      clinically relevant fetal blood groups, However, only Rh typing (D, C, c, E, and
      e) and K1 genotyping assays are discussed in this review. Importantly, one must
      remember that results of genotyping assays will not always be concordant with
      serological typing. Thus, the RhD genotyping assays have to be modified in
      response to increased understanding of the molecular biology of this blood group
      system. RhD typing assays should produce negative results when tested on the
      black RhD-negative RHD alleles, RHDpsi and r's. PCR-based assays can be used to
      determine paternal zygosity. For RhD zygosity testing, the real-time quantitative
      PCR approach and the direct detection of the hybrid Rhesus box, which is the
      result of the deletion of the RHD gene are available. Recently, methods for
      noninvasive prenatal genotyping have been investigated. The use of fetal cells
      circulating in the maternal circulation has been explored; however, the scarcity
      of circulating fetal cells has limited the use of this approach. More promising
      are the results obtained with RhD typing assays with cell-free fetal DNA, which
      is present in the maternal circulation in a concentration of 25 genomic
      equivalents per milliliter of maternal blood in early pregnancy increasing to 100
      copies per milliliter in the third trimester, which is cleared from the
      circulation within a few hours of delivery. The positive predictive value of this
      approach is virtually 100%, but false-negative results are (infrequently)
      encountered. Therefore, this assay can at present only be used for screening of
      RhD-negative women to make the use of antenatal prophylaxis more targeted and
      hence more cost-effective. For the clinical management of the pregnancies of
      alloimmunized women, the development of a control for the presence and the
      amplification of fetal DNA is needed, which is at present only available in male
      pregnancies. Assays for the genotyping of the other Rh antigens or Kell antigens
      with cell-free fetal DNA have not yet been described.

PMID- 12522771
TI  - Understanding platelet function through signal transduction.
AB  - Platelets are activated by a number of stimuli resulting in the expression and/or
      activation of surface receptors, secretion of vasoactive substances, adhesion,
      aggregation, and finally thrombus formation. These events are propagated by a
      process known as transmembrane signaling, which relays the activating signal from
      the platelet membrane (eg, von Willebrand Factor binding to glycoprotein Ib) to
      the inside of the platelet which then serves to activate the platelet via a
      cascade of biochemical interactions. Inhibition of these transmembrane signaling
      molecules with a variety of available inhibitors or antagonists can in many cases
      prevent the platelet from becoming activated. An awareness of the mechanisms
      involved in platelet transmembrane signaling and the recent availability of new
      reagents to inhibit signaling may provide us with additional means to prevent
      platelet activation and perhaps even ameliorate the platelet storage lesion. This
      review will provide an introduction to the field of platelet transmembrane
      signaling and give an overview of some of the platelet signaling mechanisms that
      are relevant to transfusion medicine.

PMID- 12522772
TI  - The clinical implications of platelet transfusions associated with ABO or Rh(D)
      incompatibility.
AB  - Despite the time elapsed since their development, and substantial human and
      economical efforts searching for alternatives, platelet transfusion, continues to
      be the main therapeutic measure available for the management of patients
      suffering from quantitative and qualitative platelet disorders. However, there
      are still aspects of their use that are not completely established. One of these
      is ABO and/or Rh(D) compatibility. A major ABO group incompatibility appears to
      decrease the response to a platelet transfusion, whereas a minor ABO
      incompatibility can be associated with, sometimes lethal, acute hemolytic
      transfusion reactions in the recipient. Other detrimental effects on the
      recipient of a minor ABO incompatibility have also been reported. In contrast,
      the main problem associated to a Rh(D) incompatible platelet transfusion is the
      development of alloimmunization of a Rh(D)-negative woman in childbearing age or
      younger. Factors like degree of patient immunosuppression and red blood cell
      content in the platelet concentrate significantly modulate the risk of
      alloimmunization. New clinical studies are needed to define clearly the current
      risk associated to ABO- and/or Rh(D)-incompatible platelet transfusions, and such
      defined risks would help establish the most cost effective measures to prevent
      the appearance of the potential complications related to platelet use.

PMID- 12522773
TI  - Cellular immune mechanisms in autoimmune thrombocytopenic purpura: An update.
AB  - Autoimmune thrombocytopenic purpura (AITP) is a bleeding disorder in which
      autoantibodies are directed against an individual's own platelets, leading to
      enhanced clearance through Fc receptor (R)-mediated phagocytosis by macrophages
      residing in the reticuloendothelial system (RES), particularly in the spleen. The
      production of IgG autoantibodies is critically dependent on cellular immune
      mechanisms particularly relating to T cells. We review the recent literature of
      the cell-mediated immunology of AITP focusing on platelet phenotype, genetics, T
      cell reactivities, and cytokine profiles in patients with AITP. Understanding the
      interaction between these cell-mediated mechanisms is vital for developing
      antigen specific immunotherapies to treat this autoimmune disease.

PMID- 12522776
TI  - Training and educational approaches to minimally invasive surgery: state of the
      art.
AB  - Current training in minimally invasive surgery (MIS) is inadequate given the
      demands of patients on practitioners and the number of surgeons and residents who
      still need to be trained. The training that is provided is neither widespread nor
      is it standardized, resulting in graduate surgeons with a wide range of
      competence. There is little guidance in what a training program needs to be
      effective. We provide a brief review of the state of the art of MIS training with
      some emphasis given to training methods including perceptual motor training, MIS
      learning laboratories, virtual reality, evaluation and assessment, cost,
      simulation fidelity, credentialing, certification, privileging, and ergonomics.
      We conclude that the state of the art is left wanting.

PMID- 12522777
TI  - Ethical and educational considerations in minimally invasive surgery training for
      practicing surgeons.
AB  - There is an opportunity to improve the training of practicing surgeons in minimal
      access techniques. Such improvement is desirable because it would allow for the
      introduction of innovation in a way that maximizes the benefit for patients while
      minimizing the harm that can result from the introduction of new techniques after
      inadequate training. This goal is consistent with basic biomedical principles
      that govern the behavior of surgeons. Individuals who place themselves in the
      role of a teacher of surgeons accept another level of responsibility and are
      governed not only by biomedical ethics but also by the ethics of teaching.
      Adherence to these two different governing ethical principles compels these
      teachers to apply the best educational principles in the development of
      educational courses. Review of motor skill learning theory would suggest that
      effective feedback and adequate practice opportunities are essential for the
      acquisition of motor skill and should be integrated into all skills-type
      continuing medical educational courses. The present trend is toward more
      objectivity in skill evaluation although evidence that this actually improves
      evaluation is lacking. Curriculum development and evaluation of this specific
      type of training course should follow those general principles proposed for the
      development of effective continuing medical education.

PMID- 12522778
TI  - Surgical endoscopy training is integral to general surgery residency and should
      be integrated into residency and fellowships abandoned.
AB  - It is a basic premise that laparoscopic procedures are an integral part of the
      practice of general surgery. Currently, general surgery training programs as a
      whole are failing to provide residents with significant surgical experience in
      advanced laparoscopic procedures. The teaching of advanced laparoscopic
      procedures can and should be incorporated into the 5-year surgical residency. The
      challenge for Program Directors is that it is time to restructure general surgery
      training so that additional fellowship training is not required to provide an
      adequate experience in this fundamental part of general surgery.

PMID- 12522779
TI  - Fellowships in minimally invasive surgery: a fait accompli.

PMID- 12522780
TI  - Does minimal access mean minimal relationship? Defining the physician-patient
      relationship in postmodern culture.
AB  - Minimal access surgery is a good example of medicine in the postmodern era. It
      embodies the problems we see in both medicine and society that affect the way
      physicians and patients interact. The purpose of this article is to evaluate and
      assess the impact of these factors on the focused relationship between the
      physician and patient. We will discuss how minimal access surgery may be the
      start of a "new medicine" to benefit both patient and physician.

PMID- 12522781
TI  - The ethics of applying new medical technologies.
AB  - Medical technology itself, including minimally invasive surgery, has no morals;
      our morality revolves around when and how we use technology. This often involves
      the individual clinician's assessment of their own abilities and an awareness of
      two aspects of the technology: its proven efficacy and its safety. Is technology
      outpacing knowledge? Or do physicians adopt new technologies in a responsible way
      with good motives? No one knows for sure. Technological progress in medicine has
      been a mixed blessing. The only ethical element involved in the use of new
      technologies over which individual medical practitioners have control, is that of
      user proficiency with the device, procedure, or drug, and the related information
      they provide to their patients when obtaining their consent for its use. New
      technologies fall into two broad categories: evolutionary, the most common, and
      revolutionary, which occur sporadically and may completely change the face of
      medical care. The learning curve for all new technologies can be steep. So, when
      should physicians be permitted to use these new technologies without supervision?
      Who is responsible for setting and monitoring standards for new technologies?
      With the moving target of medical technological innovation, individual
      practitioners are primarily responsible for the ethical use of new (to them)
      technologies. It is physicians' ethics that govern their use of new technologies,
      being certain that they have the requisite training and experience to use the
      modality, and that the intervention is safe for their patients. Institutional
      practitioner credentialing at the local level, despite its faults, will often be
      the primary control over a technology's use. What will ultimately govern the use
      of new technologies is the ethics (if they exist) of healthcare institutions and
      individual practitioners, as well as patient need. This is simply another reason
      why ethics education is vital for physicians-and other health practitioners and
      healthcare administrators.

PMID- 12522782
TI  - Laparoscopic surgery, robots, and surgical simulation: moral and ethical issues.

PMID- 12522784
TI  - The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the
      Afro-Caribbean population of the Netherlands Antilles: a family screening.
AB  - Hereditary hemorrhagic telangiectasia (HHT) has been reported rarely in people of
      African descent. The prevalence in the Afro-Caribbean population of the
      Netherlands Antilles is suspected to be high. A family screening in this
      population was done to arrive at a point prevalence and to identify patients with
      pulmonary involvement. By clinical history and physical examination, 219 persons
      over age twelve with a first-degree relative with HHT were screened. The
      diagnosis was based on the new diagnostic criteria [Shovlin et al., 2000]. Chest
      roentgenogram and pulse-oximetry or measurement of arterial oxygen pressure were
      used to detect pulmonary involvement. HHT was diagnosed in 112 individuals (51%),
      with at least a point prevalence of 1 in 1,331 inhabitants of Curacao and Bonaire
      older than twelve years. The diagnosis was uncertain in 27; this was partly due
      to the new stringent criteria. Epistaxis was present in 98% and telangiectases in
      99%. Facial telangiectases were relatively rare due to pigmented skin. Pulmonary
      involvement was found in 28% with serious-mainly neurological-complications in
      48%. The point-prevalence of HHT in the Afro-Caribbean population of the
      Netherlands Antilles is the highest known in the world. Pulmonary involvement in
      this population is not rare and causes serious complications.

PMID- 12522783
TI  - Parents' and children's attitudes toward the enrollment of minors in genetic
      susceptibility research: implications for informed consent.
AB  - PURPOSE: Children at high risk of future disease may be recruited for
      participation in disease susceptibility research involving genetic testing. This
      study was aimed at assessing parents' and children's reactions to such research,
      and their perceptions of risks and benefits of participating. METHODS: Parents
      and children (ages 10-17) from families at increased risk for breast cancer (n =
      16 dyads) and heart disease (n = 21 dyads) participated in separate audiotaped
      interviews and a follow-up family interview one year later. We asked about
      reactions, risks and benefits, and informational needs regarding participation in
      hypothetical research involving genetic testing on a saliva sample. Audiotape
      transcripts were analyzed qualitatively. RESULTS: All children would initially
      participate because they viewed the research as low risk. When thinking about
      learning their test result and sharing it with others, or the uncertainties of
      testing, many children became hesitant about participating. Many parents thought
      their child might worry about a positive result, making them unlikely to enroll
      their child, or to choose not to tell the child test results. Both children and
      parents thought the benefits of participating included early detection or
      treatment (breast cancer families), prevention (heart disease families) and
      helping others. Children's questions about research participation centered on
      details of the study design and purpose, while parents' questions related to the
      genetic test itself. CONCLUSIONS: Children's first reaction to participating in
      research involving genetic susceptibility testing research may not indicate an
      adequate appreciation of risks and benefits; if encouraged to personalize the
      impact of genetic testing, children are able to engage in a more informed
      decision-making process.

PMID- 12522785
TI  - Griscelli syndrome without hemophagocytosis in an eleven-year-old girl: expanding
      the phenotypic spectrum of Rab27A mutations in humans.
AB  - We present an eleven-year-old female patient who was referred to us with silvery
      hair, hepatosplenomegaly, neutropenia-thrombocytopenia, hypogammaglobulinemia and
      degenerative white matter disease, with a family history of a female sibling
      dying at the age of five and two living male cousins, ages 10 and 11. She had
      been followed up for her cytopenia the last three years and had totally recovered
      from a hemiplegic episode before admission. The family was of Arabic origin, and
      a second-degree consanguinity was reported between the parents. Microscopic
      analysis of her hair shafts revealed irregularly distributed small and large
      clumps of melanin, and skin biopsy findings were consistent with partial
      albinism. Bone marrow aspiration and biopsy did not detect any evidence of
      hemophagocytosis. Genetic analysis identified a homozygous two-base-pair deletion
      (51 del CT leading to S18X) in the Rab27A gene of the patient. She suffered from
      febrile neutropenic episodes. Her persistent cytopenia could not be corrected
      with immunoglobulin, thrombocyte infusions, or a short course of growth factor
      treatment. Splenectomy was planned due to her progressive splenic enlargement.
      She was also considered for bone marrow transplantation. She unfortunately died
      from an intracranial hemorrhage. Her clinical presentation was remarkable, mostly
      resembling partial albinism immunodeficiency/Elejalde syndrome due to her older
      age and absence of hemophagocytosis, but with molecular findings confirming
      Griscelli syndrome.

PMID- 12522786
TI  - Hypomelanosis, immunity, central nervous system: no more "and", not the end.

PMID- 12522787
TI  - Speech characteristics in the Kabuki syndrome.
AB  - Six children with Kabuki syndrome were studied to investigate speech patterns
      associated with the syndrome. Each child's speech was characterized with regard
      to articulation (types of errors and intelligibility), pitch (high or low),
      loudness (volume of speech), and prosody (general quality of speech that combines
      rate and inflection). All six children had a history of delayed speech and
      language acquisition and were receiving speech services. All individuals had
      articulation errors and abnormal oral resonance, which appeared to be due to poor
      oral-motor coordination and hypotonia and were not felt to be due to structural
      abnormalities such as velopharyngeal insufficiency, dental malocclusion, or cleft
      palate. An intriguing finding, noted in the two individuals followed from
      childhood into adolescence with serial speech evaluations, was that pitch,
      loudness, and prosody did not mature over time and what was age appropriate
      performance at younger ages became inappropriate in adolescence. This raises a
      challenge for speech services, as by adolescence, while articulation had
      improved, the pitch and loudness of these individuals' speech had not and so was
      noticeably different from peers. Distinctive speech characteristics with a lack
      of normal maturation during childhood can be added to the extensive list of
      clinical features associated with the Kabuki syndrome and hopefully will lead to
      improved speech/language treatment for individuals with this syndrome.

PMID- 12522788
TI  - Parental consanguinity and congenital heart malformations in a developing
      country.
AB  - The association between isolated congenital heart defects and consanguinity was
      examined in 759 Lebanese patients with different types of congenital heart
      malformations. The subjects were patients of the Children's Cardiac Registry
      Center (CCRC) at the American University of Beirut Medical Center. The proportion
      of first-cousin marriages among cardiac subjects was compared to that of the
      National Collaborative Perinatal Neonatal Network (NCPNN), after adjusting for
      the subjects' geographic distribution, and to the highest proportion reported by
      NCPNN. In general, the proportion of overall parental consanguinity and first
      cousin matings among CCRC subjects (34.7 and 20.2%, respectively) were
      significantly higher than the highest proportion of first-cousin marriages
      reported by NCPNN (Bekaa subjects; 13.2%) (P < 0.0001). Comparison with the NCPNN
      adjusted first-cousin mating proportion revealed a significantly increased rate
      of consanguinity in all categories of cardiac malformations except great vessel
      and coronary artery lesions (P < 0.05). The following lesions were significantly
      associated with increased parental consanguinity: aortic anomalies (aortic
      insufficiency, aortic stenosis, bicuspid aortic valve), atrial septal defect,
      double-outlet right ventricle, pulmonary atresia, patent ductus arteriosus,
      pulmonic stenosis, tetralogy of Fallot, and ventricular septal defect (P < 0.05).
      Higher maternal education was the only variable that was negatively correlated
      with parental consanguinity (P = 0.037). Our study emphasizes the role of
      homozygous recessive genes in the causation of different types of isolated
      congenital heart malformations, known to follow a multifactorial pattern of
      inheritance. There is an urgent need for educating the public on the deleterious
      effects of inbreeding, especially in developing countries with high overall
      consanguinity rates and limited financial resources.

PMID- 12522790
TI  - Apparent encephalocele in twin fetus papyraceus with twin-reversal arterial
      perfusion.
AB  - An apparently iniencephalic or exencephalic monoamniotic monochorionic female
      twin fetus, delivered as a fetus papyraceus at 28 weeks of gestation, had severe
      anomalies of the central nervous system and spine, including occipital
      encephalocele with a defect of the occipital bone. The encephalocele contained a
      spherical mass of autolyzed brain tissue without identifiable cerebellum or
      vermis. The cervical canal was widely patent dorsally, there were severe bony
      anomalies, including agenesis and fusion of vertebrae in the cervicothoracic
      spine. The upper limbs were absent. All organs were hypoplastic and autolyzed.
      The hypoplastic heart had three chambers. The placenta was monochorionic and
      monoamniotic; barium injection showed a twin-reversal arterial perfusion and
      entanglement of the umbilical cords.

PMID- 12522789
TI  - Gaucher disease associated with parkinsonism: four further case reports.
AB  - Type 1 Gaucher disease is considered the non-neuronopathic form of this autosomal
      recessively inherited lysosomal storage disease. We report the simultaneous
      occurrence of Gaucher disease with parkinsonian in four adult patients. The
      patients had a relatively early onset of parkinsonian manifestations, and their
      disease was rapidly progressive and refractory to therapy. Each had a different
      Gaucher genotype, although four alleles carried the common N370S mutation. No
      mutations were identified in the genes for parkin or alpha-synuclein. The
      concurrence of these two phenotypes, both in this series of patients and in
      others in the literature, suggests a shared pathway, modifier, or other genetic
      etiology.

PMID- 12522791
TI  - Double supernumerary isodicentric chromosomes derived from 15 resulting in
      partial hexasomy.
AB  - We report two unrelated patients each with two supernumerary marker chromosomes
      (SMCs) derived from chromosome 15, and thus resulting in partial hexasomy.
      Hexasomy in the one case (family 1) was diagnosed at prenatal diagnosis and did
      not include the Prader-Willi/Angelman critical region (PWACR). The double SMCs
      were also found in the mother, the pregnancy continued to term, and an apparently
      phenotypically normal child was born. This represents the first report of
      transmission of double SMCs from mother to child. In the second case (family 2),
      the hexasomy did include the PWACR and was de novo in origin. This patient
      manifested severe psychomotor retardation, clefting of the soft palate,
      hypotonia, seizure-like episodes, and other phenotypic features. The aberrant
      phenotype is attributable to the hexasomy for the PWACR gene loci. The normal
      homologs of chromosome 15 proved to be biparental in origin while the two SMCs
      appeared maternal.

PMID- 12522792
TI  - Familial lateral semicircular canal malformation with external and middle ear
      abnormalities.
AB  - We report a family with inner ear lateral semicircular canal (LSC) malformation
      and external and middle ear abnormalities. The family had no history of known
      syndromes or toxic exposures. Distinct phenotypic manifestations were found in
      three family members. A young girl exhibited bilateral LSC malformation with a
      right-sided preauricular tag, a mildly deformed auricle, a stenotic external
      auditory canal, and a constricted middle ear cavity. She had moderate conductive
      hearing loss in the right ear but normal hearing in the left ear. Her younger
      brother exhibited right-sided LSC malformation, microtia, external auditory canal
      atresia, a malformed middle ear cavity, and abnormal auditory ossicles. He had
      severe mixed hearing loss in his right ear. Their mother exhibited left-sided LSC
      malformation without external and middle ear abnormalities, and the hearing was
      normal in her left ear. None of the three cases had vestibular symptoms, and
      their results of balance tests were appropriate for the corresponding ages. In
      contrast, significantly decreased LSC function was revealed by caloric tests in
      an ear with LSC malformation. Previously, LSC malformation may have been
      underdiagnosed in patients presenting with external and middle ear abnormalities
      and their relatives, since this malformation is frequently associated with normal
      hearing and balance or conductive hearing loss only. To our knowledge, this
      condition has not been described previously. This condition supports a genetic
      basis for the combination of LSC malformation and external and middle ear
      abnormalities and may represent an autosomal dominant condition with variable
      expressivity.

PMID- 12522793
TI  - Clinical variability of type II sialidosis by C808T mutation.
AB  - Sialidosis (McKusick 256550) is an autosomal recessive disorder resulting from
      mutations in the NEU gene, located in 6p21.3, which leads to deficiency of alpha
      N-acetyl neuraminidase (sialidase) activity, causing an accumulation of its
      substrates, oligosaccharides, in the lysosomes of various organs and tissues and
      an increased presence in urine and other organic fluids. We present a clinical
      report of three patients diagnosed for type II sialidosis. The first patient is a
      12-year-old boy with the classic infantile form. His sister had a congenital form
      of sialidosis and died at 20 months of age. The third, nonrelated patient
      presented shortly after 1 year of age and had borderline cognitive delay at 9
      years. All three patients were homozygous for the C808T mutation of the NEU gene.
      Their ancestors originated from a small area to the east of the city of Seville
      (Spain), suggesting the existence of a Seville founder mutation.

PMID- 12522794
TI  - Patient with Sotos syndrome, Wolff-Parkinson-White pattern on electrocardiogram,
      and two right-sided accessory bypass tracts.
AB  - Sotos syndrome is a growth regulation disorder. Accessory conduction pathways,
      the anatomical structures responsible for Wolff-Parkinson-White syndrome, are
      thought to result from developmental failure to eradicate the remnants of the
      atrioventricular connections during cardiogenesis. Although the reported
      prevalence of congenital heart disease in Sotos syndrome is 10 times higher than
      in the general population, there are no reported cases with ventricular pre
      excitation. We report a patient with Sotos syndrome with two distinct accessory
      atrioventricular bypass tracts documented by invasive electrophysiology testing
      and a curative catheter ablation procedure.

PMID- 12522795
TI  - Patient with terminal duplication 3q and terminal deletion 5q: comparison with
      the 3q duplication syndrome and distal 5q deletion syndrome.
AB  - Partial duplication of chromosome 3q is a well-described condition of multiple
      congenital anomalies and developmental delay that resembles the Brachmann-de
      Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome
      has recently been described. The combination of both chromosome abnormalities has
      not been previously described. We report on a child with both a de novo
      duplication of distal 3q (q27 --> qter) and terminal deletion of 5q (q35.2 -->
      qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the
      dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate
      developmental delays. The phenotype is compared and contrasted to the few reports
      of patients with similar terminal 3q duplications and 5q deletions. Our patient
      did not have the characteristic phenotype of the 3q duplication syndrome,
      suggesting that the chromosome region responsible for this phenotype is more
      proximal than the terminal 3q27 region. In addition, comparison with three other
      reported cases of terminal 5q35 deletions suggests a possible association of
      terminal 5q deletions with central nervous system (CNS) structural abnormalities.

PMID- 12522796
TI  - Unknown diagnosis in two male cousins with facial abnormalities, optic atrophy,
      abnormal EEG, and severe psychomotor retardation.
AB  - We report two male cousins with short stature, microcephaly, hypertelorism, optic
      atrophy, ptosis, absent ear lobes, high-arched palates, abnormal EEG, and severe
      mental retardation. Both cousins have consanguineous parents. Differential
      diagnoses are discussed and the possibility that we might be reporting on a new
      syndrome is raised.

PMID- 12522797
TI  - Hirschsprung disease, mental retardation, characteristic facial features, and
      mutation in the gene ZFHX1B (SIP1): confirmation of the Mowat-Wilson syndrome.

PMID- 12522798
TI  - Nonsyndromic pulmonary valve stenosis and the PTPN11 gene.

PMID- 12522799
TI  - 15-Month-old infant with failure to thrive, hepatomegaly, increased liver
      enzymes, hypoproteinemia, and seizures.

PMID- 12522800
TI  - An angel with Down syndrome in a sixteenth century Flemish Nativity painting.
AB  - Artistic representation of malformation syndromes has been of ongoing interest,
      often as a point of departure for discussion of medical history. We have
      identified a 16th-century Flemish Nativity painting in which one angelic figure
      appears distinctly different from other individuals in the painting with an
      appearance of Down syndrome. Several prior observers have identified Down
      syndrome in premodern art, sometimes stimulating ongoing discussions concerning
      its history, its prevalence, and its relationship to hypothyroidism. This may be
      one of the earliest European representations of Down syndrome. The depiction of
      an individual with Down syndrome as an angel raises several questions regarding
      the status of such an individual in late medieval times and societal recognition
      of minor anomalies, as contrasted with major malformations, in their predictive
      value for disabilities. In contrast, Langdon Down's description of the condition
      occurred only after evolution of concepts regarding the clinical significance of
      physical appearance and measurement.

PMID- 12522801
TI  - Comment on Elejalde syndrome and relationship with Griscelli syndrome.

PMID- 12522802
TI  - CFC syndrome.

PMID- 12522803
TI  - Cardio-facio-cutaneous syndrome phenotype and del(12q).

PMID- 12522804
TI  - Editor's note: regarding correspondence on CFC syndrome and interstitial 12q
      deletions.

PMID- 12522805
TI  - Lack of association between ZIC2 and ZIC3 genes and the risk of neural tube
      defects (NTDs) in Hispanic populations.

PMID- 12522806
TI  - Titanium surface topography alters cell shape and modulates bone morphogenetic
      protein 2 expression in the J774A.1 macrophage cell line.
AB  - Macrophage cytokine expression significantly affects wound healing. Macrophage
      secretion of transforming growth factor beta 1 (TGFbeta1) and bone morphogenetic
      proteins (BMP) may affect osteogenesis at endosseous implant surfaces. The aim of
      this investigation was to determine the effect of commercially pure titanium
      (cpTi) substrate topography on adherent macrophage osteogenic and osteoinductive
      cytokine expression. J774A.1 murine macrophage cell adhesion was examined by
      scanning electron microscopy, 0-72 h following plating onto polished, machined,
      and grit-blasted cpTi surfaces. TGFbeta1 and BMP-2 gene expression by adherent
      macrophages was determined by the reverse transcription polymerase chain
      reaction. Macrophage adhesion increased with time on all surfaces and spreading
      increased with increasing surface roughness (polished < machined < grit-blasted).
      BMP-2 expression was not evident for cells adherent to polished cpTi at 24 h. In
      contrast, BMP-2 expression occurred at 24 h in cells adherent to machined and
      grit-blasted cpTi. BMP-2 expression was evident on all surfaces at 72 h and was
      greatest in grit-blasted titanium adherent cells. Increasing concentrations of
      cytochalasin B (0-50 microM) inhibited macrophage spreading and reduced BMP-2
      mRNA expression, suggesting a relationship between cell shape and BMP-2
      expression. This was further characterized using anti-beta1 and anti-beta3
      integrin antibodies. The anti-beta1 integrin antibodies inhibited adherent
      macrophage BMP-2 mRNA expression. Anti-beta3 integrin antibody treatment only
      modestly reduced BMP-2 mRNA expression. Endosseous implant surface topography
      induced changes in macrophage shape that were associated with changes in BMP-2
      expression in J774A.1 mouse macrophage cell line. This first demonstration of BMP
      2 expression by cpTi adherent macrophages suggests that the macrophage may
      contribute surface-specific osteoinductive signals during bone formation at
      implanted alloplastic surfaces.

PMID- 12522807
TI  - Effect of subtoxic concentrations of metal ions on NFkappaB activation in THP-1
      human monocytes.
AB  - THP-1 human monocytes and human peripheral blood monocytes have altered
      inflammatory cytokine secretion profiles after exposure to a variety of metal
      ions known to be released from biomaterials. Transcriptional regulation of these
      cytokines often involves activation of the transcription factor NFkappaB. The
      present study was designed to determine whether metal ion treatment of monocytes
      results in changes in levels of activated NFkappaB. THP-1 cells were grown in
      suspension in the presence of sublethal concentrations of ions of Ag(+), Co(2+),
      Cu(2+), Hg(2+), Ni(2+), and Pd(2+). After 24 h of exposure to metal ions, the
      cells were harvested, counted, and the nuclear proteins extracted.
      Electrophoretic mobility shift assays were performed using a (32)P-ATP end
      labeled oligonucleotide consensus sequence for the NFkappaB transcription factor.
      DNA/protein complexes were quantified by phosphorimage analysis and compared by
      ANOVA (Tukey, alpha = 0.05). Exposure of THP-1 cells to 100 microM of Pd(2+)
      caused a significant increase in activated NFkappaB (p < 0.05) whereas treatment
      with 5 microM of Ag(+) resulted in significantly decreased levels of nuclear
      NFkappaB (p < 0.05). No other metal ions tested caused a significant change in
      basal levels of nuclear NFkappaB (Co(2+), Hg(2+), Ni(2+), and Cu(2+)). However,
      exposure to 50 microM of Cu(2+) resulted in a reproducible, though not
      significant, increase in nuclear NFkappaB levels. These results indicate that
      inflammatory responses to some metal ions may be influenced by NFkappaB-mediated
      transcriptional regulation.

PMID- 12522808
TI  - Biological performance of biomimetic calcium phosphate coating of titanium
      implants in the dog mandible.
AB  - The aim of the present study was to analyze the in vivo effect of biomimetic
      calcium phosphate coating of titanium implants on periimplant bone formation and
      bone-/implant contact. Five types of implants were used: 1) Ti6Al4V implants with
      a polished surface; 2) Ti6Al4V implants with collagen coating; 3) Ti6Al4V
      implants with a mineralized collagen layer; 4) Ti6Al4V implants with sequential
      coating of hydroxyapatite (HA) and collagen; and 5) Ti6Al4V implants with HA
      coating only. All implants had square cross sections with an oblique diameter of
      4.6 mm and were inserted press fit into trephine burr holes of 4.6 mm in the
      mandibles of ten beagle dogs. The implants of five animals each were evaluated
      after a healing period of 1 month and 3 months, respectively, during which time
      sequential fluorochrome labeling of bone formation had been performed. Bone
      formation was evaluated by morphometric measurement of the newly formed bone
      around the implants and the percentage of implant bone contact. After 1 month,
      there was a significantly higher percentage of mean bone/implant contact in the
      HA-coated implants compared to those with polished surface and those with the
      collagen-coated surface. After 3 months, these differences were not present
      anymore. Bone apposition was significantly higher next to implants with
      sequential HA/collagen coating compared to polished surfaces and mineralized
      collagen layer. It is concluded that biomimetic coating of titanium implants with
      HA has shown the clearest trend to increase bone-implant contact in the early
      ingrowth period. The addition of collagen to an HA coating layer may hold some
      promise when used as sequential HA/collagen coating with mineralized collagen as
      the surface layer.

PMID- 12522809
TI  - Flow perfusion culture of marrow stromal osteoblasts in titanium fiber mesh.
AB  - The objective of this study was to evaluate the effect of two cell culture
      techniques, static and flow perfusion, on the osteogenic expression of rat bone
      marrow cells seeded into titanium fiber mesh for a period up to 16 days. A cell
      suspension of rat bone marrow stromal osteoblasts (5 x 10(5) cells/300 microL)
      was seeded into the mesh material. Thereafter, the constructs were cultured under
      static conditions or in a flow perfusion system for 4, 8, and 16 days. To
      evaluate cellular proliferation and differentiation, constructs were examined for
      DNA, calcium content, and alkaline phosphatase activity. Samples were also
      examined with scanning electron microscopy (SEM) and plastic-embedded
      histological sections. Results showed an increase in DNA from day 4 to day 8 for
      the flow perfusion system. At day 8, a significant enhancement in DNA content was
      observed for flow perfusion culture compared with static culture conditions, but
      similar cell numbers were found for each culture system at 16 days. Calcium
      measurements showed a large increase in calcium content of the meshes subjected
      to flow perfusion at day 16. The SEM examination revealed that the 16-day samples
      subjected to flow perfusion culture were completely covered with layers of cells
      and mineralized matrix. In addition, this matrix extended deep into the
      scaffolds. In contrast, meshes cultured under static conditions had only a thin
      sheet of matrix present on the upper surface of the meshes. Evaluation of the
      light microscopy sections confirmed the SEM observations. On the basis of our
      results, we conclude that a flow perfusion system can enhance the early
      proliferation, differentiation, and mineralized matrix production of bone marrow
      stromal osteoblasts seeded in titanium fiber mesh.

PMID- 12522810
TI  - Vascularization and tissue infiltration of a biodegradable polyurethane matrix.
AB  - Urethanes are frequently used in biomedical applications because of their
      excellent biocompatibility. However, their use has been limited to bioresistant
      polyurethanes. The aim of this study was to develop a nontoxic biodegradable
      polyurethane and to test its potential for tissue compatibility. A matrix was
      synthesized with pentane diisocyanate (PDI) as a hard segment and sucrose as a
      hydroxyl group donor to obtain a microtextured spongy urethane matrix. The matrix
      was biodegradable in an aqueous solution at 37 degrees C in vitro as well as in
      vivo. The polymer was mechanically stable at body temperatures and exhibited a
      glass transition temperature (Tg) of 67 degrees C. The porosity of the polymer
      network was between 10 and 2000 microm, with the majority of pores between 100
      and 300 microm in diameter. This porosity was found to be adequate to support the
      adherence and proliferation of bone-marrow stromal cells (BMSC) and chondrocytes
      in vitro. The degradation products of the polymer were nontoxic to cells in
      vitro. Subdermal implants of the PDI-sucrose matrix did not exhibit toxicity in
      vivo and did not induce an acute inflammatory response in the host. However, some
      foreign-body giant cells did accumulate around the polymer and in its pores,
      suggesting its degradation is facilitated by hydrolysis as well as by giant
      cells. More important, subdermal implants of the polymer allowed marked
      infiltration of vascular and connective tissue, suggesting the free flow of
      fluids and nutrients in the implants. Because of the flexibility of the
      mechanical strength that can be obtained in urethanes and because of the ease
      with which a porous microtexture can be achieved, this matrix may be useful in
      many tissue-engineering applications.

PMID- 12522811
TI  - An atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold)
      for the culture of annulus fibrosus cells from an intervertebral disc.
AB  - The aim of this study was to investigate the possibility of using the
      atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS-scaffold) for
      the culture of annulus fibrosus (AF) cells in tissue engineering procedures of
      intervertebral disc repair. AF cells from the intervertebral discs of Japanese
      white rabbits were cultured for up to 3 weeks in the ACHMS-scaffold to allow a
      high density, three-dimensional culture. Although the DNA content in the scaffold
      increased at a lower rate than in the monolayer culture, scanning electron
      microscopy data showed that the scaffold was filled with the grown AF cells and
      produced extracellular matrix on day 21. The amount of type II collagen and its
      mRNA expression by the scaffold cultured cells were determined using Western
      blotting and Northern blotting analyses, respectively, and remained at a higher
      level than in the monolayer cultured cells. Furthermore, glycosaminoglycan (GAG)
      accumulation in the scaffold culture was at a higher level than in the monolayer
      culture. Western blot analysis for extracted proteoglycans from the scaffold
      culture also exhibited a much higher proteoglycan accumulation than the monolayer
      culture. These results indicate that the AF cells are able to grow and remain
      phenotypically stable in the scaffold.

PMID- 12522812
TI  - Human serum albumin incorporating synthetic heme: red blood cell substitute
      without hypertension by nitric oxide scavenging.
AB  - The administration of extracellular, hemoglobin-based oxygen carriers often
      elicits an acute increase in blood pressure by vasoconstriction. This side effect
      is now recognized to be due to the depletion of nitric oxide (endothelial-derived
      relaxing factor) by the extravasuated hemoglobins. We have recently found that
      the administration of a recombinant human serum albumin (rHSA)-based oxygen
      carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA
      FeP) does not induce such hypertensive action, because of its low permeability
      through the vascular endothelium. The heart rate responses after the rHSA-FeP
      injection were also negligibly small. Visualization of the intestinal
      microcirculatory changes clearly revealed the widths of the venule and arteriole
      to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising
      material as a new type of red blood cell substitute.

PMID- 12522813
TI  - Sugar-mediated chitosan/poly(ethylene glycol)-beta-dicalcium pyrophosphate
      composite: mechanical and microstructural properties.
AB  - The microstructural and mechanical properties of sugar-mediated
      chitosan/poly(ethylene glycol)-based scaffolds and composites, which are composed
      of beta-dicalcium pyrophosphate (beta-DCP) and sugar-mediated scaffolds, were
      investigated. All of the scaffolds were prepared by various freeze-drying
      protocols. The differences in the freeze-drying process of the sugar-mediated
      chitosan/poly(ethylene glycol) scaffold for three types of sugar (sucrose,
      glucose, and D-fructose) were determined by scanning electron microscopic
      observation, water retention, density, and porosity analyses. The sugar-mediated
      scaffolds prepared by scheme I of the freeze-drying process show large pores,
      poorly connective interlayers, and disintegrated inner structures, different from
      the small pores and well-connective channel structures as shown in the scheme II
      freeze-drying process. The key factors for controlling pore structure and size in
      the scheme I freeze-drying process were formulation and composition, but for the
      scheme II freeze-drying process, the key factor was freeze protocol. The
      composite scaffolds were macroporous, and the microstructure changed considerably
      with added beta-DCP content. The incorporation of beta-DCP granules caused a
      significant enhancement of compressive modulus and yield strength. The increased
      mechanical strength may be attributable not only to the physical complexation
      between the sugar-mediated scaffold and beta-DCP, but also the chemical reaction
      to apatite formed on the cell wall.

PMID- 12522814
TI  - Chondrogenesis of human mesenchymal stem cells encapsulated in alginate beads.
AB  - Mesenchymal stem cells (MSCs) have the capacity for self-renewal and can form
      bone, fat, and cartilage. Alginate forms a viscous solution when dissolved in
      0.9% saline and gels on contact with divalent cations. The viability and
      phenotype maintenance of chondrocytes in alginate beads have been well
      documented. However, little is known about the effect of microencapsulation in
      alginate on chondrogenesis of MSCs. In this study, human MSCs encapsulated in
      alginate beads were cultured in serum-free medium with the addition of
      transforming growth factor (TGF)beta1 (10 ng/mL), dexamethasone (10(-7) M), and
      ascorbate 2-phosphate (50 microg/mL). The MSCs in alginate assumed a rounded
      morphology with lacunae around them after 1 week in culture. Cell aggregates were
      observed at 2 weeks or longer in culture. Histological findings agreed with the
      clinical determination of hyaline cartilage, characterized by isolated cells with
      ground substance positive in Safranin-O staining and immunohistochemistry for
      collagen type II at the periphery of cells. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) revealed the expression of COL2A1 and COL10A1, marker of
      chondrocytes and hypertrophy chondrocytes, respectively. These results indicate
      MSCs in alginate can form cartilage and the MSCs-alginate system represents a
      relevant model for the study of the molecular mechanisms involved in the
      chondrogenesis and endochondral ossification.

PMID- 12522815
TI  - Aggregation behaviors and their pH sensitivity of cholesterol-conjugated
      proteinoids composed of glutamic acid and aspartic acid matrix.
AB  - Cholesterol-conjugated proteinoids and their aggregation behaviors were
      investigated with model proteinoid systems. Model proteinoids of molecular
      weights in the range of 4000 to 6000 were synthesized by anhydrous thermal
      condensation forming a matrix with glutamic acid and aspartic acid and of
      naturally occurring amino acids. Nuclear magnetic resonance and Fourier transform
      infrared spectra suggested that cholesterol was conjugated to carboxyl group
      forming pendants. Native water-soluble proteinoids can form microspheres in
      acidified or heated conditions, but the cholesterol-conjugated proteinoids were
      found to form aggregates in water, regardless of the temperature or pH of the
      solutions. The hydrophobic pendant moieties come to a compact association in
      core, whereas the hydrophilic chains provide a shield layer.

PMID- 12522816
TI  - Porous PEOT/PBT scaffolds for bone tissue engineering: preparation,
      characterization, and in vitro bone marrow cell culturing.
AB  - The preparation, characterization, and in vitro bone marrow cell culturing on
      porous PEOT/PBT copolymer scaffolds are described. These scaffolds are meant for
      use in bone tissue engineering. Previous research has shown that PEOT/PBT
      copolymers showed in vivo degradation, calcification, and bone bonding. Despite
      this, several of these copolymers do not support bone marrow cell growth in
      vitro. Surface modification, such as gas-plasma treatment, is needed to improve
      the in vitro cell attachment. Porous structures were prepared using a freeze
      drying and a salt-leaching technique, the latter one resulting in highly porous
      interconnected structures of large pore size. Gas-plasma treatment with CO(2)
      generated a surface throughout the entire structure that enabled bone marrow
      cells to attach. The amount of DNA was determined as a measure for the amount of
      cells present on the scaffolds. No significant effect of pore size on the amount
      of DNA present was seen for scaffolds with pore sizes between 250-1000 microm.
      Light microscopy data showed cells in the center of the scaffolds, more cells
      were observed in the scaffolds of 425-500 microm and 500-710 microm pore size
      compared to the ones with 250-425 microm and 710-1000 microm pores.

PMID- 12522817
TI  - Study of novel chitosan-gelatin artificial skin in vitro.
AB  - A novel absorbable scaffold composed of chitosan and gelatin was fabricated by
      freezing and lyophilizing methods, resulting in an asymmetric structure. This
      bilaminar texture is suitable for preparing a bilayer skin substitute. The
      methods employed to confirm the applicability of this chitosan-gelatin scaffold
      as an ideal skin substitute were a water uptake ability test, in vitro fibroblast
      proliferation, and scaffold tests in which fibroblasts were co-cultured with
      keratinocytes. The chitosan-gelatin scaffolds were more wettable and adsorbed
      more water than did chitosan alone. In static cell culture the thinner scaffold
      is better than the thicker one, and because of diffusion limitations in the
      scaffold, culture time must be within 3 weeks before transplantation to living
      tissues. Keratinocytes were co-cultured with fibroblasts in chitosan-gelatin
      scaffolds to construct an artificial bilayer skin in vitro. The artificial skin
      obtained was flexible and had good mechanical properties. Moreover, there was no
      contraction observed in the in vitro cell culture tests. The data from this study
      suggest that chitosan-gelatin scaffolds are suitable for skin tissue engineering
      goals.

PMID- 12522818
TI  - Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or
      poly(dimethyl siloxane). III. In vivo biocompatibility and biostability.
AB  - To investigate the effects of polymer chemistry and topology (linear or graft
      copolymer) on in vivo biocompatibility and biostability based on cage implant
      system, various hydrogels, composed of short hydrophilic [polyethylene oxide
      (PEO)] and hydrophobic block, were prepared by polycondensation reaction.
      Poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS) was chosen as
      a hydrophobic block because of their wide utilization as a biomaterial. By using
      the specimens retrieved from rats killed after 1, 2, 3, 5, and 7 weeks'
      implantation, cellular and material responses were assessed. Most hydrogels
      showed a comparable value of macrophage density to Pellethane(R), control
      polymer, whereas they did significantly lower foreign body giant cell (FBGC)
      density and coverage because of the presence of PEO. However, PEO block length
      and polymer topology did not affect macrophage adhesion and FBGC formation in our
      polymer composition. The hydrogel based on PDMS alone showed significantly lower
      macrophage density and FBGC density than Pellethane(R), indicating that PDMS
      plays a role in inhibiting cellular adhesion. The results obtained from gel
      permeation chromatography curve and Fourier transform infrared spectra exhibited
      that all the polymers were susceptible to oxidative degradation in vivo. Although
      Pellethane(R) revealed surface degradation by 5 weeks in vivo, hydrogels showed
      rapid degradation in the bulk within 2 weeks because of the penetration of
      oxidative chemicals released from phagocytic cells into PEO domain of phase
      separated hydrogels. The more significant degradation was observed in the
      hydrogels with longer PEO block and PTMO as a hydrophobic block instead of PDMS.
      It was evident that the minor degradation could be achieved by grafting PEO and
      adopting PDMS as a hydrophobic block in the hydrogel.

PMID- 12522819
TI  - In vivo leukocyte cytokine mRNA responses to biomaterials are dependent on
      surface chemistry.
AB  - An in vivo mouse cage implant system was used to determine whether leukocyte
      cytokine mRNA responses to implanted biomaterials were dependent on surface
      chemistry. Surfaces displaying various chemistries (hydrophobic, hydrophilic,
      anionic, and cationic) were placed into stainless steel cages and implanted
      subcutaneously. Semiquantitative RT-PCR analyses revealed that hydrophilic
      surfaces showed a decreased expression of proinflammatory cytokines, IL-6 and IL
      8, and pro-wound healing cytokines, IL-10 and TGF-beta by adherent cells, and
      mRNA levels of the proinflammatory cytokine, IL-1beta, and the pro-wound healing
      cytokine IL-13 were decreased in surrounding, exudate cells. Cytokine responses
      by adherent and exudate cells to hydrophobic, anionic and cationic surfaces were
      similar and indicative of a strong inflammatory response at the earliest time
      point followed by a wound healing response at later time points. However, no
      differences in the types or levels of exudate cells for any of the surfaces or
      the empty cage at each of the respective time points were observed, indicating
      their respective biocompatibility. These studies identify hydrophilic surface
      chemistries as having significant effects on leukocyte cytokine responses in vivo
      by decreasing the expression of inflammatory and wound healing cytokines by
      inflammatory cells adherent to the biomaterial as well as present in the
      surrounding exudate.

PMID- 12522820
TI  - Comparison of chemical treatments on the chain dynamics and thermal stability of
      bovine pericardium collagen.
AB  - A new approach for the replacement of heart valves consists of obtaining an
      acellular matrix from animal aortic valves that performs mechanically, is
      nonantigenic, and is free from calcification and fibroblast proliferation. Novel
      biochemical treatments must be developed for this purpose. In this work, we focus
      on the characterization of collagen in acellular bovine cardiovascular tissues,
      fresh or glutaraldehyde treated, and stored in different solutions [phosphate
      buffered saline (PBS), ethanol, octanol, and glutaraldehyde], to determine
      whether the resulting fibrous material is structurally preserved. The
      preservation of the triple helical structure of collagen is checked by
      differential scanning calorimetry (DSC), which is a well suited technique to
      analyze thermal transitions in proteins, such as denaturation. To get insight
      into the molecular dynamics of collagen in the nanometric range, we used
      thermally stimulated currents, a dielectric technique running at low frequency,
      that measure the dipolar reorientations in proteins submitted to a static
      electrical field. The combined use of these two techniques allowed us to evaluate
      the physical structure and conformation of collagen after the different chemical
      treatments. We have found that the glutaraldehyde treatment followed by octanol
      storage preserves the triple helical conformation of the polypeptidic chains of
      collagen, contrary to the ethanol and PBS storage that induce drastic changes in
      the thermal and dielectric behavior of the protein. Moreover, this particular
      chemical treatment stabilizes the collagen structure (shift toward high
      temperature of the collagen denaturation and stiffening of the chains by a cross
      linking action) when compared to the control sample, and so could provide
      interesting fibrous material for the conception of bioprosthetic heart valve.

PMID- 12522821
TI  - Formation and growth of clusters in conventional and new kinds of simulated body
      fluids.
AB  - Simulated body fluid (SBF) with ion concentrations approximately equal to those
      of human blood plasma has been widely used for the in vitro assessment of the
      bioactivity of artificial materials and for the formation of bonelike apatite on
      various substrates. Ion concentrations of conventional SBF (c-SBF) are, however,
      not exactly equal to those of blood plasma, and hence the apatite formed in c-SBF
      is not the same as bone apatite in its composition and structure. Recently, the
      present authors prepared new kinds of SBFs (r-SBF, i-SBF, and m-SBF) with ion
      concentrations nearer to those of blood plasma. The r-SBF and i-SBF have ion
      concentrations equal to those of blood plasma in total and dissociated amounts,
      respectively. The m-SBF has ion concentrations equal to those of blood plasma in
      total amount except for the HCO(-) (3) concentration, which was set to the
      saturated level with respect to calcite. In the present study, the stabilities of
      c-SBF, r-SBF, i-SBF and m-SBF were examined in terms of cluster formation in the
      fluids by means of dynamic light scattering photometry. The c-SBF and m-SBF were
      found to form only calcium phosphate clusters, whose initial hydrodynamic
      diameter was approximately 1 nm, and this did not change with storage time at
      36.5 degrees C. Besides the calcium phosphate clusters, r-SBF and i-SBF formed
      calcium carbonate clusters, whose initial hydrodynamic diameters were 10-30 nm,
      and these increased significantly with storage time. The formation and growth of
      calcium carbonate clusters in r-SBF and i-SBF can be attributed to their
      supersaturation with respect to calcite. These indicate that r-SBF and i-SBF lack
      long-term stability. The m-SBF is recommended for the assessment of bioactivity
      of artificial materials as well as the formation of bonelike apatite on various
      substrates from the viewpoint of stability as well as similarity to blood plasma.

PMID- 12522822
TI  - Surface-dependent conformations of human plasma fibronectin adsorbed to silica,
      mica, and hydrophobic surfaces, studied with use of Atomic Force Microscopy.
AB  - Human plasma fibronectin (Fn) is a large flexible protein stabilized by
      intermolecular ionic interactions forming a compact structure. On altering
      solution conditions, the structure can revert to a more expanded state, thereby
      exposing previously hidden domains (e.g., cell-binding sites). Electron
      microscopy images of Fn air-sprayed onto mica surfaces show elongated protein
      structures, indicating a surface-induced structural change. This makes it
      interesting to investigate the influence of surface properties on the structure
      of adsorbed Fn. We have used intermittent-contact Atomic Force Microscopy to
      investigate the structure of Fn adsorbed onto mica, silica, and methylated silica
      surfaces. We observed that on silica surfaces, which is hydrophilic, most (70%)
      of the molecules had an elongated structure with partial intramolecular chain
      interactions, compare to molecules adsorbed on hydrophobic, methylated surfaces,
      where a compact structure predominated (70%). On mica surfaces, both compact and
      elongated protein structures were observed, with a slight preference for the
      elongated form (53%). Results show that surface physical properties influence the
      molecular structure of fibronectin on adsorption, which could provide useful
      information in understanding surface-induced in vivo responses.

PMID- 12522823
TI  - Polymer design for corneal epithelial tissue adhesion: pore density.
AB  - A porous polymer is required to sustain corneal epithelial tissue on the anterior
      surface of an implantable contact lens (corneal onlay). Porosity creates
      topography on the polymer surface and, if defined, this can be manipulated to
      elicit a particular tissue response. Previous work identified pores of 100-nm
      diameter to be the critical size of a discontinuity in a polymer surface to
      facilitate the migration, stratification, and sustained adhesion of corneal
      epithelial tissue. Now we address the issue of pore density. Corneal epithelial
      tissue was grown for 21 days on nonporous polycarbonate and polycarbonate track
      etched with pores 100-nm diameter with pore densities ranging from 0.27 and 14.4%
      of the total polymer surface area. Histology was used to score epithelial
      structure, and electron microscopy was used to quantitate the formation of
      adhesive structures (basal lamina and hemidesmosomes) at the tissue-polymer
      interface. Data showed that epithelial tissue stratified and epithelial adhesive
      structures formed on polycarbonate surfaces with pore densities between 0.52 and
      14.4% inclusive. This means that epithelial tissue can be maintained on a polymer
      where up to 14.4% of the surface is dedicated to small discontinuities in the
      form of pores 100-nm diameter. These figures can be used to specify the design of
      a polymer for applications requiring epithelial cover.

PMID- 12522824
TI  - Behavior of the bone-titanium interface after push-in testing: a morphological
      study.
AB  - Fourteen titanium dental implants (Tioblast) were implanted singly in the
      proximal tibia of New Zealand rabbits for 120 days. A bone defect was surgically
      produced and filled with Bio-Oss around six of these implants. After the animals
      were sacrificed and their organs harvested, bone segments were fixed and
      methacrylate embedded after the push-in test had been performed. Microradiography
      was performed on longitudinal sections of the implants, whereas scanning electron
      microscope analysis was performed on the remaining embedded half-implants using
      secondary electrons only. The results showed that the implants were apically and
      coronally surrounded by bone, whether Bio-Oss was used or not. Fractures were
      evident through the newly formed bone and between the pre-existing and newly
      formed bone. Some fracture lines propagated through the bone and stopped at the
      implant surface without continuing along the bone-titanium interface. Detachment
      between the implant and the bone occurred at the coronal extremity of the
      implants and along its cervical region. These results highlight the fact that the
      bone-titanium interface has a high resistance to loading. It exhibited greater
      resistance than the newly formed bone and seems to behave in a manner similar to
      the cement lines of osteons.

PMID- 12522825
TI  - Optical spectroscopy and imaging of the dentin-enamel junction in human third
      molars.
AB  - A 351-nm laser excitation source was used to perform autofluorescence microscopy
      of dentin, enamel, and the dentin-enamel junction (DEJ) to obtain information
      regarding their morphology and spectral characteristics. The emission spectra of
      these calcified dental tissues were different from one another, and this enabled
      the DEJ to be imaged and dimensionalized. The DEJ displayed sharp and clearly
      delineated borders at both its enamel and dentin margins. The dentinal tubules
      and the enamel prisms appeared to terminate abruptly at the DEJ. The median DEJ
      width was 10 microm, ranging from 7 to 15 microm, and it did not appear to depend
      on intratooth position.

PMID- 12522826
TI  - In vitro and in vivo degradation of biomimetic octacalcium phosphate and
      carbonate apatite coatings on titanium implants.
AB  - Calcium phosphate (Ca-P) coatings have been applied onto titanium alloys
      prosthesis to combine the srength of metals with the bioactivity of Ca-P. It has
      been clearly shown in many publications that Ca-P coating accelerates bone
      formation around the implant. However, longevity of the Ca-P coating for an
      optimal bone apposition onto the prosthesis remains controversial. Biomimetic
      bone-like carbonate apatite (BCA) and Octacalcium Phosphate (OCP) coatings were
      deposited on Ti6Al4V samples to evaluate their in vitro and in vivo dissolution
      properties. The coated plates were soaked in alpha-MEM for 1, 2, and 4 weeks, and
      they were analyzed by Back Scattering Electron Microscopy (BSEM) and by Fourier
      Transform Infra Red spectroscopy (FTIR). Identical coated plates were implanted
      subcutaneously in Wistar rats for similar periods. BSEM, FTIR, and
      histomorphometry were performed on the explants. In vitro and in vivo, a
      carbonate apatite (CA) formed onto OCP and BCA coatings via a dissolution
      precipitation process. In vitro, both coatings dissolved overtime, whereas in
      vivo BCA calcified and OCP partially dissolved after 1 week. Thereafter, OCP
      remained stable. This different in vivo behavior can be attributed to (1)
      different organic compounds that might prevent or enhance Ca-P dissolution, (2) a
      greater reactivity of OCP due to its large open structure, or (3) different
      thermodynamic stability between OCP and BCA phases. These structural and
      compositional differences promote either the progressive loss or calcification of
      the Ca-P coating and might lead to different osseointegration of coated implants.

PMID- 12522827
TI  - Bone formation on two-dimensional poly(DL-lactide-co-glycolide) (PLGA) films and
      three-dimensional PLGA tissue engineering scaffolds in vitro.
AB  - For some bone tissue engineering strategies, direct contact of newly synthesized
      bone with a scaffold is important for structural continuity and stability at the
      scaffold/bone interface. Thus, as the polymer degrades, the support function of
      the scaffold could be adopted by the developing bone structure. This study was
      designed to determine whether poly(DL-lactide-co-glycolide) with a comonomer
      ratio of 75:25 supports bone apposition in vitro. Osteogenic cells derived from
      rat bone marrow cells were cultured for 2 weeks on polymeric two-dimensional
      films and three-dimensional tissue engineering scaffolds. Bacteriological grade
      polystyrene and tissue culture polystyrene dishes served as negative and positive
      controls for interfacial bone deposition, respectively. The surfaces of the
      prepared substrates were characterized by X-ray photoelectron spectroscopy,
      dynamic water contact angle, scanning electron microscopy, and atomic force
      microscopy. After cell culture, the elaborated matrix was examined using scanning
      electron microscopy, transmission electron microscopy, and energy dispersive
      spectroscopy. The results show that poly(DL-lactide-co-glycolide) supports
      appositional bone growth on both two-dimensional films and three-dimensional
      scaffolds, including the formation of a mineralized cement line matrix.
      Furthermore, surface topographical features are not required for the adherence of
      the cement line matrix to the polymer.

PMID- 12522829
TI  - Magnitude and characteristics of arthritis and other rheumatic conditions on
      ambulatory medical care visits, United States, 1997.
AB  - OBJECTIVE: To describe ambulatory medical care utilization, defined to exclude
      injury-related visits, for persons with arthritis and other rheumatic conditions.
      METHODS: National estimates, rates, and other characteristics of ambulatory care
      visits were calculated from a national sample of patient visits to physician
      offices and acute care hospital outpatient and emergency departments. RESULTS: An
      estimated 36.5 million ambulatory care visits were related to arthritis and other
      rheumatic conditions. Visit rates increased with age and, overall, were twice as
      high among women as men. Rates of visits by race varied by ambulatory care
      setting. Soft tissue disorders (9.3 million), osteoarthritis (7.1 million),
      nonspecific joint pain/effusion (7.0 million), and rheumatoid arthritis (3.9
      million) were the most common diagnoses. CONCLUSIONS: Arthritis and other
      rheumatic conditions account for about as many ambulatory care visits as
      cardiovascular disease or essential hypertension. These visits serve as excellent
      opportunities to counsel patients regarding prevention messages for arthritis.

PMID- 12522830
TI  - Evaluation of the smallest detectable difference in outcome or process variables
      in ankylosing spondylitis.
AB  - OBJECTIVE: To evaluate the smallest detectable difference (SDD) of symptomatic
      outcome or process variables in ankylosing spondylitis (AS) patients from various
      countries. METHODS: Thirty consecutive AS patients with axial involvement were
      recruited from 1 center in each of 4 countries (Spain, Morocco, France, The
      Netherlands), for a total of 120 patients. Fourteen variables were studied in 6
      domains: pain (3 variables), stiffness (1 variable), function (2 variables),
      spinal mobility (3 variables), patient global assessment (4 variables), and the
      domain of enthesiopathy (1 variable). All patients were evaluated twice within a
      1-week period during which no clinical or therapeutic change occurred.
      Intracenter reliability was evaluated using the intraclass correlation
      coefficient (ICC). The SDD was determined using the Bland-Altman method. RESULTS:
      Of the 14 variables evaluated in the 120 patients (82% males, 42 +/- 12 years
      old, with a mean disease duration of 17 +/- 13 years), only the SDD for the
      variable occiput-to-wall distance showed statistically significant difference
      among centers. For the entire group, the SDD, expressed as percentage of the
      range of the variable, varied from 10% (Mander enthesis index) to 39% (spinal
      pain at night last week). The intraobserver reliability was good (ICC > 0.80)
      except for the variables morning stiffness and modified Schober test (ICCs of
      0.76 and 0.60, respectively). CONCLUSION: This study suggests that the evaluation
      of AS patients is homogenous and reliable in different centers of different
      European and North African countries. Evaluation of the SDD of the symptomatic
      outcome or process variables is a starting point to determine the minimum
      clinically important difference, permitting the presentation of results of
      clinical studies on an individual basis.

PMID- 12522831
TI  - Arthritis beliefs and self-care in an urban American Indian population.
AB  - OBJECTIVE: To describe beliefs and self-care strategies of American Indians with
      chronic arthritis joint pain. METHOD: In-depth interviews were conducted with a
      convenience sample of urban-dwelling American Indians (n = 56) concerning self
      care and beliefs about arthritis; objective measures of arthritis disease
      activity were obtained through standardized interview protocols. RESULTS: Joint
      pain was not generally assumed to be arthritis nor directly related to aging.
      Belief that chronic pain affecting multiple joints was a serious and unexpected
      condition oriented American Indians' decisions to seek medical attention.
      However, verbal communications about pain may be subtle or under emphasized. Few
      coping strategies were used to control either chronic or episodic pain.
      CONCLUSIONS: Chronic arthritis pain may not be optimally managed in this
      population. Cultural assessment should recognize that American Indian patients
      may understate serious symptoms. Community educational interventions should
      target this population to enhance self-care, pain management, and communication
      of arthritis symptoms to physicians.

PMID- 12522832
TI  - Use of NSAIDs, COX-2 inhibitors, and acetaminophen and associated coprescriptions
      of gastroprotective agents in an elderly population.
AB  - OBJECTIVES: To identify determinants of cyclooxygenase 2 (COX-2) inhibitor versus
      nonsteroidal antiinflammatory drug (NSAIDs) or acetaminophen prescription in
      seniors; and to compare gastroprotective agent coprescriptions. METHODS:
      Administrative medical records were obtained from the government of Quebec health
      insurance agency. Three cohorts were formed based on prescriptions at study
      entry: COX-2 inhibitors, NSAIDs, or acetaminophen. Logistic regressions were used
      to adjust for potential confounders. RESULTS: We identified 42,267 patients
      taking COX-2 inhibitors, 8,235 taking NSAIDs, and 19,716 taking acetaminophen.
      Determinants of utilizing COX-2 inhibitors versus NSAIDs and versus
      acetaminophen, respectively, include: female gender (odds ratio [OR] 1.47; 95%
      confidence interval [95% CI] 1.39-1.55 and OR 1.17; 95% CI 1.12-1.22);
      musculoskeletal diseases (OR 1.87; 95% CI 1.76-2.00 and OR 2.20; 95% CI 2.10
      2.31); and prior gastrointestinal hospitalization (OR 1.82; 95% CI 1.19-2.78 and
      OR 0.77; 95% CI 0.64-0.92). Gastroprotective agent coprescriptions were lower
      with COX-2 inhibitors than NSAIDs: OR 0.53; 95% CI 0.48-0.58. CONCLUSIONS: COX-2
      inhibitors were more commonly used than NSAIDs in patients with musculoskeletal
      diseases and those with prior gastrointestinal hospitalizations. Adjusted odds
      ratios showed a 47% decrease in gastroprotective agent coprescriptions with COX-2
      inhibitors compared with NSAIDs.

PMID- 12522833
TI  - Measuring exercise-induced mood changes in fibromyalgia: a comparison of several
      measures.
AB  - OBJECTIVE: To compare scales measuring exercise-induced changes in mood. METHODS:
      Mood changes in a randomized, 23-week controlled trial of exercise were assessed
      using the Beck Depression Inventory (BDI), Center for Epidemiologic Studies
      Depression Scale (CES-D), State Trait Anxiety Inventory (STAI), Fibromyalgia
      Impact Questionnaire, and the Mental Health Inventory (MHI). Effect sizes and t
      tests were computed on 23-week change scores. Scales were deemed to be confounded
      if items addressed sleep disturbances, fatigue, or effort (symptoms of both mood
      disturbances and fibromyalgia). RESULTS: Efficacy (15 exercise subjects) and
      intent-to-treat analyses (27 exercise subjects) generated medium effects for BDI
      (total, cognitive), MHI depression (efficacy only), and CES-D (intent-to-treat
      only) scales. BDI (total, cognitive), MHI (depression, positive affect, total
      [MHI-5]), and STAI scales distinguished exercise from control subjects at 23
      weeks in all analyses. BDI somatic and CES-D scales were deemed to be confounded.
      CONCLUSION: We recommend the BDI cognitive, STAI, and MHI-5 scales to measure
      depression, anxiety, and general mood, respectively, in patients with
      fibromyalgia.

PMID- 12522834
TI  - Renal underexcretion of uric acid is present in patients with apparent high
      urinary uric acid output.
AB  - OBJECTIVE: To compare renal handling of uric acid in patients with primary gout
      with that of a control group. METHODS: A case-control study of 100 patients with
      primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric
      acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric
      acid, excretion of uric acid per volume of glomerular filtration, urinary uric
      acid to creatinine ratio, and glomerular uric acid filtered load were calculated
      using 24-hour urine samples. After treatment with allopurinol to achieve similar
      glomerular filtered load of uric acid, patients were again compared with
      controls. RESULTS: Patients with gout showed lower uric acid clearance,
      fractional excretion of uric acid, excretion of uric acid per volume of
      glomerular filtration, and urinary uric acid to creatinine ratio than controls at
      baseline, when patients showed hyperuricemia. Although the glomerular uric acid
      filtered load was much higher in patients with gout than controls, 24-hour uric
      acid excretion was not statistically different. After treatment with allopurinol,
      and achieving similar uric acid filtered loads, patients still showed lower
      figures than controls. When patients with 24-hour urinary uric acids levels >700
      mg/day were compared with controls, they had lower uric acid clearance and
      fractional excretion of uric acid than controls, both at baseline and after
      achieving similar filtered loads with allopurinol therapy. CONCLUSIONS: Renal
      underexcretion is the main mechanism for the development of primary hyperuricemia
      in gout, but even patients showing apparent high 24-hour uric acid output show
      lower uric acid clearance than controls, indicating that relative, low-grade
      underexcretion of uric acid is at work.

PMID- 12522836
TI  - Minor impact of juvenile arthritis on nutritional status in young adult patients.
AB  - OBJECTIVE: Growth abnormalities and poor nutritional status have been reported in
      children with juvenile idiopathic arthritis (JIA). The aim of this study was to
      evaluate the impact of juvenile chronic rheumatic disease on current nutritional
      status in adult patients in remission or with active disease. METHODS: One
      hundred thirty-eight women and 82 men, aged >20 years, with JIA were studied
      after a mean disease duration of 15.5 +/- 2.3 years. Eighty-four (61%) of the
      women and 49 (60%) of the men were in remission. Forty-one healthy women and 54
      healthy men served as a reference group. Body composition was analyzed by dual
      energy x-ray absorptiometry. RESULTS: There was no difference in height or body
      mass index (BMI) between patients and healthy subjects. However, female patients
      with systemic disease had significantly reduced BMI compared with those with
      pauciarticular JIA (P < 0.001), and female patients who used or had been using
      corticosteroids had significantly lower weight, height, and BMI compared with the
      patients who had never used corticosteroids (P < 0.05). Female patients in
      remission had significantly more lean body mass compared with healthy controls (P
      < 0.05) and significantly less body fat was found in both women and men (P < 0.01
      for both). Patients with active disease had the same amount of lean body mass as
      the healthy controls, but significantly less body fat (P < 0.05 for women and P <
      0.01 for men). CONCLUSION: Adult patients with JIA had attained normal height,
      weight, and BMI, with the exception of women with systemic JIA and those who were
      using or had used corticosteroids. Patients with JIA in remission seemed to have
      a better nutritional status than healthy subjects.

PMID- 12522835
TI  - Interstitial lung disease in polymyositis and dermatomyositis.
AB  - OBJECTIVES: To assess prevalence, characteristics, and long-term outcome of
      interstitial lung disease (ILD) in polymyositis (PM) and dermatomyositis (DM). To
      determine predictive variables of ILD course in PM/DM, and to define both
      clinical and biochemical features associated with ILD onset in PM/DM. METHODS:
      The medical records of 156 consecutive PM/DM patients in 3 medical centers were
      reviewed. RESULTS: Thirty-six PM/DM patients (23.1%) developed ILD. We observed
      that 19.4% of patients with ILD had resolution of pulmonary disorders, whereas
      25% experienced ILD deterioration. Morbidity and mortality rates were as high as
      13.9% and 36.4%, respectively, in PM/DM patients with ILD. Parameters of PM/DM
      that related to ILD poor outcome were identified as follows: Hamman-Rich-like
      pattern, initial diffusing capacity of carbon monoxide <45%, neutrophil
      alveolitis, and histologic usual interstitial pneumonia. Additionally, for the
      group with ILD, polyarthritis, higher values of erythrocyte sedimentation rate
      and C-reactive protein, presence of anti-Jo-1 antibody, and characteristic
      microangiopathy were significantly more frequent. CONCLUSION: Our series
      underlines the high frequency of ILD in PM/DM patients, resulting in increased
      morbidity and mortality rates. It also indicates that PM/DM patients should
      routinely be screened for ILD, even those patients without anti-Jo-1 antibody,
      because 69% of our ILD patients were seronegative for the anti-Jo-1 antibody. Our
      findings further suggest that PM/DM patients presenting with factors predictive
      of ILD poor outcome may require more aggressive therapy.

PMID- 12522837
TI  - Barriers to treatment adherence among African American and white women with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether African Americans with systemic lupus
      erythematosus (SLE) have poorer treatment adherence than whites, and to determine
      ethnic group differences in barriers to adherence, and how barriers affect
      adherence. METHODS: We compared 68 African American and 54 white women with SLE
      on 19 potential barriers, on 2 adherence behaviors during the past year, and on
      how the potential barriers relate to each nonadherence behavior. RESULTS: African
      Americans and whites were similar on most barriers, although African Americans
      were more likely to rely on religion and were more concerned about long-term
      medication effects. The 2 ethnic groups were comparable on medication
      nonadherence, but whites tended to have poorer clinic appointment adherence than
      African Americans. Finally, we found that barriers related to negative affect
      (depression, medication concerns, physical symptoms) as well as short-term memory
      problems and the need for child or elder care were associated with nonadherence
      among African Americans, whereas perceived treatment inefficacy and lacking trust
      in physicians were associated with nonadherence among whites. CONCLUSION:
      Relationships between adherence barriers and nonadherence may be ethnicity
      specific, suggesting that interventions to address barriers should be targeted to
      specific groups.

PMID- 12522838
TI  - Attentional functioning in fibromyalgia, rheumatoid arthritis, and
      musculoskeletal pain patients.
AB  - OBJECTIVES: To investigate whether chronic pain patients have deficits in
      attentional functioning compared with pain-free controls, and whether
      fibromyalgia patients have larger deficits in attentional functioning compared
      with rheumatoid arthritis and musculoskeletal pain patients. METHODS: Sixty
      patients (20 in each of 3 patient groups) and 20 pain-free controls completed
      measures assessing pain intensity, mood, pain-related disability, somatic
      awareness, and catastrophic thinking about pain. Attentional functioning was
      assessed using an age-standardized, ecologically valid test battery. Analyses
      were made of between-group differences. RESULTS: Sixty percent of patients had at
      least one score in the clinical range of neuropsychological impairment,
      independent of demography and mood. Fibromyalgia patients were more anxious and
      somatically aware than rheumatoid arthritis or musculoskeletal pain patients, but
      did not show larger attentional deficits than other patient groups. CONCLUSION:
      All 3 groups of chronic pain patients, regardless of diagnosis, had impaired
      cognitive functioning on an ecologically sensitive neuropsychological test of
      everyday attention.

PMID- 12522839
TI  - Trajectory of assistive device usage and user and non-user characteristics: long
      handled bath sponge.
AB  - OBJECTIVES: To examine use of an assistive device, a long-handled bath sponge
      (LHBS) in patients with rheumatoid arthritis and osteoarthritis to describe use
      from the time of in-hospital prescription to the 2- and 12-month followups, and
      to describe the characteristics of those who became device users and non-users.
      METHODS: Patients (n = 102) who were prescribed a LHBS during hospitalization
      were followed prospectively. The clinical and psychosocial assessment included
      disease, physical and psychosocial factors, and disability. RESULTS: The overall
      usage rate for the LHBS was 86%. When compared with users, non-users had fewer
      arthritic joints, perceived greater control over their disability and pain, and
      had less favorable perceptions of the LHBS. Characteristics that did not
      differentiate non-users from users were sociodemographic variables, disease
      duration, movement capability, level of disability and pain, and general
      perceptions of assistive devices. CONCLUSION: The results support the early
      identification of patients who are likely to become non-users so that acceptable
      alternative interventions can be planned.

PMID- 12522840
TI  - Hip fracture patients are not treated for osteoporosis: a call to action.
AB  - OBJECTIVE: To determine whether hip fracture patients, a group at very high risk
      for additional fragility fractures, are being evaluated and treated effectively
      for osteoporosis. METHODS: Clinical and bone densitometry (dual x-ray
      absorptiometry [DXA]) records were reviewed in hip fracture patients at 4
      Midwestern US health systems to determine the frequency of DXA use, calcium and
      vitamin D supplementation, and antiresorptive drug treatment. RESULTS: DXA was
      performed at the 4 study sites in only 12%, 12%, 13%, and 24% of patients,
      respectively. Calcium and vitamin D supplements were prescribed in 27%, 1%, 3%,
      and 25% of the patients at the 4 study sites. Antiresorptive drugs were
      prescribed in 26%, 12%, 7%, and 37% of the patients with only 2-10% receiving a
      bisphosphonate. CONCLUSION: Reducing osteoporotic fractures will require more
      effective approaches to managing hip fracture patients and other high-risk
      populations.

PMID- 12522841
TI  - Cost effectiveness of adding leflunomide to a 5-year strategy of conventional
      disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To estimate, from a public payer's perspective, the 5-year cost
      effectiveness of adding leflunomide (LEF) to a sequence of disease-modifying
      antirheumatic drugs (DMARDs) representative of a typical rheumatoid arthritis
      (RA) management approach adopted by Canadian rheumatologists. METHODS: A DMARD
      sequence including LEF was compared with one excluding it, using a 5-year
      simulation model where patients with RA cycle through different treatment
      regimens. Data were obtained through a systematic literature search (drug
      withdrawal rates, number and type of adverse events, American College of
      Rheumatology 20% responder status) and separately conducted surveys (choice of
      DMARD sequence, management of adverse events). Costs for adverse event management
      were calculated using the Ontario Schedule of Benefits, and monitoring costs were
      calculated according to official Canadian product monograph recommendations.
      Wholesale prices of all drugs were adjusted by the allowable markup and
      prescription fees. Utilities (as measured by the standard gamble [SG] and rating
      scale [RS] techniques) were obtained from 482 patients who participated in a 1
      year randomized controlled trial that compared LEF, methotrexate, and placebo.
      Costs and utilities were discounted by 3%. Probabilistic sensitivity analysis was
      performed. RESULTS: Adding LEF to a conventional strategy of DMARDs increased the
      5-year management costs by $1,231 compared with the strategy without LEF, which
      results in a cost-effectiveness ratio of $13,096 per additional year of response
      to treatment, and cost-utility ratios of $54,229 (RS) and $71,988 (SG) per
      quality-adjusted life-year gained. CONCLUSION: Adding LEF as a new option to a
      conventional sequence of DMARDs extends the time patients may benefit from DMARD
      therapy at a reasonable cost effectiveness and cost utility. LEF data are limited
      to clinical trials; data from observational studies would be needed to
      corroborate these findings.

PMID- 12522842
TI  - Benign angiopathy of the central nervous system: cohort of 16 patients with
      clinical course and long-term followup.
AB  - OBJECTIVE: Benign angiopathy of the central nervous system (BACNS) is a subset of
      primary angiitis of the central nervous system (PACNS) with favorable outcome,
      not requiring prolonged immunosuppression. We retrospectively studied the
      clinical characteristics and prospectively assessed long-term outcome in a cohort
      of BACNS patients. METHODS: Patients meeting the clinical description for BACNS,
      evaluated and treated by a single investigator, were included. Data on
      demographics, signs and symptoms, laboratory studies, neuroimaging, brain biopsy,
      treatment, and complications were recorded. The long-term assessment included a
      phone interview utilizing the Barthel index and a specifically designed cognitive
      index. RESULTS: Sixteen cases met the inclusion criteria. Mean age was 40 years
      (range 10-66 years) with female:male ratio of 4.3:1 and a mean followup period of
      35 months (0-128 months). Headache was the most common presenting symptom, seen
      in 88% of the cases, followed by focal symptoms (63%), and diffuse symptoms
      (44%). All patients had highly abnormal cerebral angiography, and magnetic
      resonance imaging abnormalities were present in 77% (10 of 13). Severe cerebral
      spinal fluid (CSF) abnormalities were present in 1 patient (7%). All followup
      cerebral angiography showed marked improvement. Recovery was demonstrated in 94%
      of the patients, 6% relapsed, and there were no deaths. Of patients assessed by
      the Barthel index, 71% showed no disability and 29% had mild disability.
      CONCLUSION: There is a PACNS subset characterized by acute presentation (most
      commonly headache), normal to mildly abnormal CSF findings, female predominance,
      and highly abnormal cerebral angiography (reversible after treatment), requiring
      less intensive treatment than has been traditionally used.

PMID- 12522843
TI  - Methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid
      arthritis.

PMID- 12522844
TI  - Occupational therapy for rheumatoid arthritis: a systematic review.

PMID- 12522845
TI  - Update: treatment of osteoarthritis.

PMID- 12522846
TI  - Comment on steroid hormones and disease activity during pregnancy in systemic
      lupus erythematosus.

PMID- 12522847
TI  - A reply to comments on sociocultural issues in clinical research: unraveling the
      Tuskegee syphilis study.

PMID- 12522849
TI  - Giant cell arteritis with a low erythrocyte sedimentation rate: comments on the
      article by Salvarani and Hunder.

PMID- 12522851
TI  - The Childhood Myositis Assessment Scale to assess muscle function in a patient
      with juvenile dermatomyositis.

PMID- 12522853
TI  - Low quality of care from DHMOs.

PMID- 12522854
TI  - Similar procedures?

PMID- 12522855
TI  - A privilege to be licensed.

PMID- 12522856
TI  - Testing for nitrous oxide.

PMID- 12522857
TI  - Achieving anatomic proximal contacts with direct composite resin restorations.

PMID- 12522858
TI  - Update on dentin desensitization.

PMID- 12522859
TI  - Developments in indirect resin composite materials.

PMID- 12522860
TI  - Selecting biocompatible dental alloys for patients.

PMID- 12522861
TI  - Bridging the gap: clinical protocol and case study.

PMID- 12522862
TI  - A high-tech, high-touch approach to developing a cosmetic practice.

PMID- 12522863
TI  - Ultrasonic probing: the wave of the future in dentistry.

PMID- 12522864
TI  - Office planning for the 21st century: considerations for the geriatric patient.

PMID- 12522865
TI  - Dr. Hygiene, RDH, Part 2.

PMID- 12522866
TI  - Hand conditions can have multiple causes.

PMID- 12522867
TI  - Antibiotic resistant bacteria a global crisis.

PMID- 12522868
TI  - Dentists can help prevent osteoradionecrosis.

PMID- 12522869
TI  - Oral care important for pediatric cancer patients.

PMID- 12522870
TI  - Full-mouth disinfection improves severe periodontitis.

PMID- 12522871
TI  - All-in-one solution and unique delivery system reduce steps.

PMID- 12522872
TI  - [National Audit Bureau--patients' best friend].

PMID- 12522873
TI  - [From code culture to vital knowledge].

PMID- 12522874
TI  - [Who is to control the money flow?].

PMID- 12522875
TI  - [Laparoscopic surgery in Norway].
AB  - BACKGROUND: Laparoscopic procedures in gastrointestinal surgery have increasingly
      been used over the last ten years. This study explores the use of various common
      laparoscopic procedures in Norway. METHODS: A questionnaire was sent to all 59
      public hospitals in Norway in January 1999, of which all but one responded.
      Laparoscopic surgery was performed in 54 out of 58 hospitals. RESULTS: Most
      hospitals perform between 11 and 20% of all gastrointestinal operations with
      laparoscopic technique. Laparoscopic cholecystectomies and anti-reflux surgery
      have generally replaced open procedures in all hospitals. Appendectomy by the
      laparoscopic technique accounts for approximately 10% of cases and has become the
      preferred technique in only one of ten hospitals. Laparoscopic hernia repairs are
      done in less than 10% of cases. Overall, surgeons' satisfaction with laparoscopy
      is good and seems slightly higher in district and central hospitals than in
      university hospitals. Half of all surgical departments plan to use more
      laparoscopic procedures. INTERPRETATION: Laparoscopic procedures have replaced
      conventional open surgical procedures for some procedures but is less used than
      expected ten years ago. A slow and gradual increase may be expected in the years
      ahead.

PMID- 12522876
TI  - [Fetal growth, pre-eclampsia and adult breast cancer risk].
AB  - BACKGROUND: Studies of the association between birth weight and future breast
      cancer risk have shown inconsistent results, but women born after preeclamptic
      pregnancies may have a risk reduction of more than 50% compared to other women.
      In this review we have examined the literature on the association between
      perinatal factors and adult risk of breast cancer. MATERIAL AND METHODS: We
      searched Medline for published literature until February 1, 2002 and included
      references that were not available through Medline, but have been referenced in
      other articles. RESULTS: Papers published until the beginning of 2002 suggest
      that birth weight is positively, but not strongly, associated with future risk of
      breast cancer. On the other hand, women who were exposed to preeclampsia in utero
      have a striking reduction in breast cancer risk compared to women whose mothers
      had uncomplicated pregnancies. Besides, dizygotic twins appear to be at increased
      risk, whereas monozygotic twins may have a reduced risk of breast cancer,
      compared to the general population. INTERPRETATION: The literature published
      until the beginning of 2002 suggests that factors that operate in utero are
      associated with future risk of breast cancer. Factors that increase growth
      velocity may be related to increased risk, whereas factors with anti-oestrogenic
      properties may have a protective effect.

PMID- 12522877
TI  - [Lymphedema after surgical treatment of cervical and vulvar cancer].
AB  - BACKGROUND: Lack of information after surgery for cervical cancer to women who
      are at risk of developing lymphoedema can lead to delay in diagnosis and
      treatment of this side effect. MATERIAL AND METHODS: Former patients with
      cervical cancer and vulvar cancer were asked whether they remembered having been
      counselled about lymphoedema post-operatively and whether they were satisfied
      with the information received. 83 out of 92 returned a mailed questionnaire
      assessing the standard of the information given before discharge. RESULTS: 30% of
      the patients were satisfied with the information given. About 30% reported that
      they had received neither written nor oral information about lymphoedema. 18
      women stated the importance of oral information. 20% had symptoms of lymphoedema
      of the lower limbs. INTERPRETATION: The study confirms the importance of patient
      education given verbally before discharge. Health personnel with extensive
      knowledge and experience in the area should give this information.

PMID- 12522878
TI  - [Deep vein thrombosis and localized rhabdomyolysis in a patient with bladder
      cancer].
AB  - BACKGROUND: Rhabdomyolysis is caused by skeletal muscle injury that results in
      the release of intracellular contents into the circulatory system. In certain
      cases, potentially fatal conditions may develop. Multiple conditions followed by
      muscular necrosis may lead to rhabdomyolysis. MATERIAL AND METHODS: We present a
      case history of a patient with bladder cancer in whom deep vein thrombosis was
      complicated by rhabdomyolysis. The patient developed acute renal failure. We have
      also searched the literature for similar cases. RESULTS AND INTERPRETATION: The
      patient did not respond to the treatment given. In order to save his life, the
      affected extremity was amputated. Rhabdomyolysis is a very rare complication of
      deep vein thrombosis. There are only a few patients described in the literature
      in which these conditions occur simultaneously. The diagnosis of rhabdomyolysis
      can easily be missed, as the two conditions give almost identical symptoms.

PMID- 12522879
TI  - [Postpartum hemorrhage--prophylaxis and treatment in Norway].
AB  - BACKGROUND: Routine oxytocic prophylaxis is known to significantly reduce the
      risk of severe postpartum haemorrhage (> 1,000 ml) and need for blood transfusion
      after delivery. To what extent this evidence is implemented in clinical practice
      in Norway is not known. MATERIAL AND METHODS: A telephone questionnaire survey
      was carried out in September 2001 to evaluate the routine clinical practice for
      prevention and treatment of postpartum haemorrhage in Norwegian delivery units.
      RESULTS: Data were available for 55 out of 57 institutions with a delivery unit.
      Routine third stage prophylaxis with 5-10 IU oxytocin was practiced in 47% of
      delivery units. Intravenous oxytocin infusion was used primarily in all the
      delivery units for the treatment of established primary postpartum haemorrhage.
      74% of units used methylergometrine, 21% misoprostol as the second-line
      treatment. INTERPRETATION: Despite evidence for the use of oxytocics for the
      prevention of postpartum haemorrhage, less than half of delivery units in Norway
      practice routine prophylaxis in the third stage of labour. Norwegian women may
      benefit if all maternity care providers implement evidence-based practice.

PMID- 12522880
TI  - [Electronic medical records in somatic hospitals--availability and clinical use].
AB  - BACKGROUND: Despite the fact that 53 out of 72 Norwegian hospitals (as of January
      2001) have introduced electronic medical records systems (EMR), very few
      evaluation or comparisons between such systems have been published. MATERIAL AND
      METHODS: We developed a questionnaire for physicians with items on computer
      literacy, use of electronic medical records and user satisfaction that was sent
      in January 2001 to 314 hospital physicians. 227 physicians responded (72%).
      Details about local system implementation were collected through telephone
      interviews with key IT personnel in each hospital. RESULTS: EMR functions were
      available for a total of 15 out of 23 tasks listed in our questionnaire. The
      majority of physicians used EMR for between two and seven tasks that mainly
      covered reading patient data, though respondents scored highly on computer
      literacy (72.2/100). INTERPRETATION: There is a substantial discrepancy between
      the reported use of EMR systems and the functions available in the systems. The
      causes are not known, but lack of computer literacy is a less probable cause.

PMID- 12522881
TI  - [Drugs against symptomatic, benign prostatic hyperplasia].

PMID- 12522882
TI  - [Medical birth registry--an essential resource in perinatal medical research].
AB  - Based on compulsory notification and operative since 1967 the Medical Birth
      Registry of Norway comprises all births in the country after 16 weeks gestation.
      The notification form is filled in by the midwife and the doctor and contains
      civil data on mother, father and the newborn as well as medical data on mother's
      health before and during the pregnancy, on the birth, including complications,
      and on the newborn, including birth defects and other congenital conditions. All
      diagnoses recorded before discharge from the hospital are included. From 1998,
      diagnoses recorded after transfer to a paediatric department and throughout the
      first year of life are notified as well. The registry data are used for
      epidemiological surveillance of birth defects and other perinatal health
      problems, for evaluation of health services and as a basis for perinatal
      epidemiological research; follow-up studies based on internal and external record
      linkage are essential.

PMID- 12522883
TI  - [The central population registry in medical research].

PMID- 12522884
TI  - [Cause of death registry--an important data source for medical research].
AB  - Statistics on mortality and cause of death are of crucial importance to
      epidemiological research. The Cause of Death Register kept by Statistics Norway
      is the only national register including information on cause of death for all
      deceased persons registered as residents in Norway at their time of death,
      whether death occurred in Norway or abroad. This article presents historical
      information and guidelines for research access to individual data on cause of
      death.

PMID- 12522885
TI  - [Use of patient registries in surgery].

PMID- 12522887
TI  - [Ophthalmoscopy in the Tidsskriftet].

PMID- 12522886
TI  - [Not true about antioxidants].

PMID- 12522888
TI  - [Lung cancer].

PMID- 12522889
TI  - [Incorrect use of acid-suppressive medications in hospitalized patients].

PMID- 12522890
TI  - [Use of acid-suppressive medications in hospitalized patients].
AB  - INTRODUCTION: The acid-suppressive medications are used frequently in
      hospitalized patients, but some studies suggests that their are overused,
      especially in the treatment of stress ulcer prophylaxis in low-risk patients.
      This research determine the frequency of use and indications of acid-suppressive
      medications in hospitalized patients in a internal medical service. MATERIALS AND
      METHODS: A at random and retrospective revision of 209 medical records of 661
      hospitalized patients during the year 2000 in the V Internal Medical Service of
      the General University Hospital of Gregorio Maranon (Cantoblanco). DEFINITIONS:
      Use: any prescription of an acid-suppressive medication, regardless of dosage
      regimen, in which the patient received at least one dose. Appropriated
      indication: endoscopical criteria: treatment of active ulcer disease, esophagitis
      or gastritis. Medical criteria: symptomatic gastroesophageal reflux, dyspepsia,
      prolonging of previous treatment, as a part of a treatment regimen for H. pylori,
      relief of dyspepsia caused by nonsteroidal anti-inflammatory drugs, stress ulcer
      prophylaxis in high risk patients. Inappropriate indication: any other uses were
      considered not indicated. RESULTS: Of the 209 patients, a total of 157 (75.1%)
      received acid-suppressive therapy, average age 76 years old, 89 women (56.7%) and
      68 men (43.3%). The admitting diagnoses for the admission were: CHF 34 (21.7%),
      Pneumonia (16.6%), UTI (15.3%) y COPD 18 (11.5%). The use in hospital ward was
      84.7% (133), with inappropriate use 72.2% (96), the cause of prescription "no
      reason" 52.1% (50), and received proton pump inhibitors 46.9% (45). CONCLUSIONS:
      This study show a high frequency of incorrect use of acid-suppressive medications
      in hospitalized patients.

PMID- 12522891
TI  - [Usefulness of the tumor markers in the diagnosis of idiopathic deep venous
      thrombosis associated cancer].
AB  - OBJECTIVE: To evaluate a wide detection of tumor markers practiced during
      admission for the diagnosis of cancer in patients with idiopathic deep venous
      thrombosis. MATERIAL AND METHODS: Prospective study including 48 patients with
      documented DVT who lacked a predisposing cause to DVT. It was determined in
      serum: carcinoembryonic antigen, alphafetoprotein, CA 19-9, CA 125, beta-2
      microglobulin, SCC (squamous cell antigen), NSE (neuron-specific enolase), PSA
      (prostate-specific antigen) in the males and CA15-3 in the women. The patients
      were evaluated for cancer during admission and followed up at 6 and 12 months.
      RESULTS: The age was 65 years. A positive tumor marker at least was detected in
      23 patients (48%). A cancer was diagnosed in 8 patients (16%), 4 in the group
      with elevated tumor markers and 4 in the group with normal tumor markers. We
      don't find significant differences in cancer incidence between both groups.
      However, of the 4 cases of cancer diagnosed in the group with elevated markers
      only 1 was considered true positive since in the others three cases the elevate
      tumor marker was not appropriated with the cancer diagnosed. Six tumors were
      diagnosed during admission and two during follow-up period. According to these
      results was obtained a sensitivity of 12%, a specificity of 52%, a positive
      predictive value of 5% and a negative predictive value of 75%. CONCLUSIONS: The
      cancer incidence is similar to previous series. We have found a poor sensitivity,
      specificity and positive predictive value. However, the negative predictive value
      was of 75% and the patients who were normals for results of all tumor markers and
      was asymptomatic during admission hadn't a subsequent cancer diagnosis.

PMID- 12522892
TI  - [Contribution of Galician hospitals to national and international Internal
      Medicine scientific meetings].
AB  - OBJECTIVES: To evaluate the scientific contributions of internal medicine
      services from Galicia to nationals and internationals specialty meetings and to
      describe theirs preferences in clinical research. MATERIAL AND METHOD: We
      analysed the communications from the Abstracts books of the last four Spanish
      Internal Medicine National Congress (1994-2000 period) in comparison with that of
      1984, the last two European Congress (1999 and 2001) and the last World Congress
      (2000). Case reports were excluded. RESULTS: An increasing number of
      communicating hospitals and a sustained number of reports was observed with a
      minimum of 2 hospitals (1984) to a maximum of 12 (1996) with 5-6 hospitals on
      average. Number of communications became stable and reached 5% of the whole
      spanish reports. Cardiovascular and AIDS-Infectious diseases were the preferred
      research fields. CONCLUSIONS: An increment of scientific communications from a
      growing number of galician hospitals was observed. This scientific production
      became continuous and stabilized notoriously on cardiovascular and AIDS
      infectious disease fields.

PMID- 12522893
TI  - [Comparison of the antihypertensive activity of fosinopril and irbesartan].
AB  - OBJECTIVE: To compare the antihypertensive effect of two daily single dose drugs
      acting on the renin-angiotensin axis by two different ways. METHODS: Thirty
      patients were randomized to receive either irbesartan (150 mg once daily) (n =
      15, mean age 65.2 +/- 8.7 years, 9 men and 6 women) or fosinopril (20 mg once
      daily) (n = 15, mean age 57.4 +/- 11.5 years, 4 men and 11 women, difference are
      not significant) during 12 weeks. When needed, hydroclorothiazide (12.5 mg) was
      added to treatment to improve hypotensive response. RESULTS: A reduction of SBP
      and DBP was observed in both treatment groups throughout the study. In order to
      obtain further BP reduction, hydrochlorothiazide was added to 6 patients with
      inadequate BP response at the 4th week (3 patients in the irbesartan group) and
      8th week (2 patients in irbesartan group and 1 patient in fosinopril group). SBP
      was reduced in irbesartan group from 157.7 +/- 11.2 to 131.0 +/- 8.7 mmHg (12th
      week, p < 0.001). DBP decreases from 94.1 +/- 5.6 to 82.7 +/- 4.2 mmHg (p <
      0.001). In fosinopril group SBP was reduced from 147.9 +/- 11.7 to 132.2 +/- 12.4
      mmHg (p < 0.001) and DBP decreases from 92.3 +/- 6.3 to 84.0 +/- 5.4 mmHg (p <
      0.001). Final between group differences in BP are not significant. Final BP
      reduction in irbesartan group (26.7 +/- 11.6 mmHg) was bigger than that obtained
      in fosinopril group (15.6 +/- 11.6 mmHg, p = 0.011). BP reduction was significant
      in fosinopril group from the first month (SBP 140.7 +/- 12.2, p = 0.021; DBP 87.2
      +/- 6.2, p = 0.003). In irbesartan group BP reduction was not significant until
      the second month (SBP 135.5 +/- 10.4, p < 0.001; DBP 85.3 +/- 4.3, p < 0.001).
      CONCLUSIONS: Fosinopril and irbesartan seems to be equally effective to reduce
      DBP. Irbesartan might have higher effectiveness on systolic blood pressure.
      Irbesartan act more gradually than fosinopril and this may be useful to prevent
      from acute blood pressure falls.

PMID- 12522894
TI  - [Chronic mesenteric ischemia due to superior mesenteric artery stenosis.
      Percutaneous therapy as alternative treatment].
AB  - Chronic mesenteric arterial ischemia is an uncommon condition associated with a
      high morbidity and mortality. It is most commonly caused by atherosclerotic
      occlusive disease. Patients may suffer epigastric or periumbilical post-prandial
      pain ten to thirty minutes after eating. A case of chronic mesenteric ischemia is
      presented due to superior mesenteric artery stenosis. The diagnosis was performed
      with doppler sonography and angiography and was treated with percutaneous
      transluminal angioplasty. The patient became completely asymptomatic. The purpose
      of this report is to present the case, clinic and radiological features and to
      describe the percutaneous procedure. We believe that percutaneous treatment
      offers an improvement in this pathology with a low complication rate, decreasing
      the admission days and increasing patient comfort degree.

PMID- 12522895
TI  - [Unusual metastasis of differentiated thyroid carcinoma].
AB  - Distant metastases of differentiated thyroid cancer are usually localised in the
      lung and bone; less common sites of metastases are the brain, liver, and skin. To
      find it in other sites it is exceptional. This work shows the clinical,
      histological and therapeutical characteristic of primary tumour in three cases of
      non-typical distant metastases of differentiated thyroid cancer. Follicular
      thyroid carcinoma was displayed in two cases, the first presented one metastases
      in right adrenal gland and the second in left kidney. Both cases were initially
      treated only with hemithyroidectomy, without posterior radioiodine. In one case,
      elevated serum thyroglobulin did not receive radioiodine treatment because Whole
      Body Scintigraphy was negative. The thirst case was a papillary thyroid carcinoma
      treated with total thyroidectomy, ablative radioiodine and suppressor therapy
      with levothyroxine. However, posterior evolution was unfavourable and tumour
      presented metastases in common and less common sites like choroid. Histological
      study showed tall cell variant of papillary thyroid carcinoma. In summary, when
      the initial treatment of well-differentiated thyroid carcinoma it is inaccurate,
      it is possible to find common and less common sites metastases. Some variants of
      papillary thyroid carcinoma, like tall cell, have a worse prognosis and they can
      present metastases in less common sites.

PMID- 12522896
TI  - [Ochronosis: a case report with multisystemic affectation, including
      pericardium].
AB  - Alkaptonuric ochronosis is rare disorder of tyrosin catabolism with an autosomal
      recessive trait. Alkaptonuric patients are deficient for homogentisate 1,2
      dioxygenase. This enzymatic deficiency leads to the elimination of large amounts
      of homogentistic acid in the urine (Alkaptonuria) with accumulation of
      homogentistic acid oxidized pigment in the connective tissue (Ochronosis). The
      most common clinical features are dark brown discoloration of urine on exposure
      to air; ocular and cutaneous pigmentation; calcification of the intervertebral
      disc and cardiovascular ochronosis, especially calcification and stenosis of the
      aortic valve. The diagnosis is confirmed by detection of homogentistic acid in
      urine. We report a case of a 87 year old female which has all these clinical
      features mentioned above and pericardiac calcification, which had not been
      previously reported, to our knowledge.

PMID- 12522897
TI  - [Pulmonary carcinosarcoma with skin metastasis].
AB  - We describe a case of lung carcinosarcoma in a 70-years-old patient with chronic
      obstructive pulmonary disease. Pulmonary carcinosarcoma is an unfrequent lung
      tumor, and usually histologic diagnosis is carried out by microscopic examination
      of the resected tumor. We observed these situation in our patient that was
      diagnosed of squamous cell carcinoma before the surgical resection by
      transthoracic needle aspiration. One month after surgery he developed a lesion in
      the infranasal area that was identified as a skin metastasis of lung
      carcinosarcoma. There is no previously reported case of skin metastasis of this
      rare tumor of the lung, that contain an admixture of malignant epithelial and
      mesenchymal elements. Clinical symptoms of pulmonary carcinosarcomas are not
      different from other lung tumors. The treatment when it is possible is the
      surgical resection of the tumor. We review histologic, diagnostic and therapeutic
      features of lung carcinosarcomas.

PMID- 12522898
TI  - [Economic class syndrome].
AB  - Comfort, safety and time saving makes air travel more and more popular and widely
      use by an increased number of people in a range of extended age frame. Recent
      concerns in the global news have again raised an issue about the association of
      thromboembolic disease and air travel. Although there are numerous studies in the
      literature examining venous thromboembolic disease (VTE), variability of
      population demographics makes difficult a right and prospective assessment in the
      context of the cabin environment and air travel. Literature review clearly
      demonstrate that VTE is multicausal in nature, resulting in differing etiologic
      and predisposing factors across different age groups. Many questions are still to
      be answered, How many cases?, Direct association to Air Travel?, How to prevent
      it in the aviation environment? In this paper we analyze the incidence of VTE and
      some additional epidemiological aspects, risk and predisposing factors,
      diagnostic, and preventive measures given by the airline, the user, aviation
      authorities, aeromedical especialist in order to cope this complication. Finally
      we discuss the physiopathological bases in which VTE is developed and related
      considerations of this syndrome in the context of the aviation environment.

PMID- 12522900
TI  - [Syndrome of inappropriate antidiuretic hormone secretion as the first
      manifestation of an occult small cell lung carcinoma].

PMID- 12522899
TI  - [Behcet's disease therapy review].
AB  - Behcet's disease is an inflammatory process of unknown origin, which usually
      presents with recurrent oral ulcers, genital aphthae, uveitis and cutaneous
      lesions. However, a wide variety of clinical manifestations have been reported,
      and virtually any organ system may be affected, showing central nervous system,
      joints, blood vessels or gastrointestinal tract involvement. Therapeutic approach
      remains complex, and varies in basis of the affected organs. Complex aphthosis
      may respond to topical therapy, colchicine and dapsone. If this therapy does not
      result in adequate disease control, thalidomide, oral prednisone and methotrexate
      may be useful. When severe ocular lesions or systemic manifestations are present,
      therapies tend to be more aggressive, usually combining corticosteroids with
      immunosuppressive agents as cyclosporin, azathioprine, cyclophosphamide,
      interferon-alfa-2a, and chlorambucil.

PMID- 12522901
TI  - [Interferon therapy for herpes simplex virus infection in a 70 years old
      patient].

PMID- 12522902
TI  - [Pneumatosis intestinalis in a patient with necrotic myopathy].

PMID- 12522904
TI  - [Metachronous small cell lung carcinoma and stomach adenocarcinoma].

PMID- 12522903
TI  - [Mycobacterium marinum infection].

PMID- 12522905
TI  - [Jaw swelling: a case report of cervicofacial actinomycosis].

PMID- 12522906
TI  - [Bilateral intracranial hemorrhage following thrombolytic therapy with alteplase
      (rTPA) in acute myocardial infarction].

PMID- 12522907
TI  - [Myasthenic syndrome].

PMID- 12522908
TI  - [Cutaneous angiosarcoma and bilateral pulmonary bleeding].

PMID- 12522909
TI  - [Pulmonary parenchymal infiltrates on thoracic CT of a patient in treatment with
      amiodarone].

PMID- 12522910
TI  - [Hot themes].

PMID- 12522911
TI  - [Biological warfare. I. Anthrax, plague, tularemia].

PMID- 12522912
TI  - [Radioactive drugs. Modern diagnosis and treatment with "hot drugs"].

PMID- 12522914
TI  - [Publication of clinical studies. CONSORT statement].

PMID- 12522913
TI  - [Clopidogrel. Actions, pharmacokinetics, clinical studies].

PMID- 12522915
TI  - [Traumatology due to ancient lead missile projectiles].
AB  - The lead missiles of slingers in antiquity, known as glans or molybdis, are
      widely considered to have been very dangerous projectiles of the ancient armies.
      Ballistic investigations and results of experimental archaeology seem to confirm
      this. However, the findings of medical history concerning these missiles disagree
      with this view. In ancient medical texts these missiles are only mentioned
      sporadically, as in Celsus or Paul of Aigina, and wounds caused by them are
      merely discussed incidentally. There is so far no evidence at all on them in
      palaeopathology. It is undisputed however that in individual cases these missiles
      were able to cause serious injuries, especially when they hit unprotected parts
      of the body. Accordingly, their main effect seems to have consisted in the
      intimidation of the enemy.

PMID- 12522916
TI  - [Peace policy by accusations of heresy against Johannes Crato (1519-1585) and
      denunciation of Paracelcius followers as Arians].
AB  - Since 1563 the Paracelsians were publicly denounced as Arians who denied the full
      divinity of Christ. A work of Alexander von Suchten, who was personal physician
      of the Polish King, triggered the polemic. The "Propositiones" of Suchten
      outlined a doctrine of salvation based on chemistry and medicine. As can be
      proved the pamphlet was influenced by heterodox christologies and doctrines of
      justification. But there are no indications of contacts between Suchten and
      Polish antitrinitarians of his time. Actually the public denunciation of the
      Paracelsians as Arians was a clever political move of the Emperor's personal
      physician Johannes Crato who aimed at the reformation of medicine in a humanistic
      sense. This aim was threatened by the fundamental opposition of the Paracelsians,
      exactly as his irenic religious policy was jeopardized by the growing
      confessional dogmatism. In this situation Crato used the instrument of
      denunciation as a means to dissociate himself from medical and theological
      extremists. The Zurich naturalist Konrad Gessner supplied him with the basic
      idea. Thomas Erastus, medical professor in Heidelberg, worked out the accusation
      in detail.

PMID- 12522917
TI  - [On the track of "scientific pursuit". Franz Josef Kallmann (1897-1965) and
      genetic racial research].
AB  - When the National Socialist state was created in 1933, an exodus of anti-Nazi
      elite began. However, some researchers who were forced to leave Germany approved
      Nazi eugenic politics, even as Jews. One of them was the psychiatrist Franz Josef
      Kallmann, a researcher on schizophrenia, who demanded an even more radical
      sterilization policy than the Nazis. He co-operated closely with the German
      Research Foundation for Psychiatry in Munich and its leader, Ernst Rudin. From
      Rudin he received help in leaving Germany and finding a job in USA, and Rudin's
      assistant, Theo Lang, delivered data-material from Munich to New York. After 1945
      Rudin got a denazification certificate from Kallmann who already co-operated
      again with Lang.

PMID- 12522918
TI  - [Diagnosis and treatment in polypous lesions of the gallbladder].
AB  - Experience in observation and treatment of 193 patients with polypous lesions of
      the gallbladder (PLGB) was analyzed. The patients were divided into 2 groups:
      group 1 consisted of 102 operated patients including ones with polypous
      cholesterosis (59), hyperplastic polyps (21), adenomatous polyps (19), polyform
      cancer (3). Group 2 consisted of 91 non-operated patients. The structure of the
      disease was studied. Clinical and morphological classification of PLGB,
      indications for surgery and follow-up were developed. Proposed algorithm of
      diagnostic and treatment policy permits to reduce surgical activity in PLGB by
      68.6% without detriment for diagnosis and treatment of polyform cancer of the
      gallbladder.

PMID- 12522919
TI  - [Injuries of cervical great vessels].
AB  - Results of surgical treatment of 156 patients with cervical vessels injuries over
      10-year period were analyzed. The majority of the wounds (82.7%) located in zone
      II of the neck. There were 143 (91.7%) stab-knife and 12 (7.7%) shotgun wounds.
      Combination of vascular traumas with injuries of deep cervical structures was in
      16 (10%) patients. Detailed physical examination permits to avoid special device
      examinations before surgery in the majority of cases. When injuries of the
      esophagus or respiratory tract were suspected, the patients underwent diagnostic
      esophago- and bronchoscopy before and during surgery. Diagnostic and therapeutic
      policies in these kinds of injuries are systematized.

PMID- 12522920
TI  - [Radiodiagnosis of acute appendicitis].
AB  - Sixty acute appendicitis suspects with unclear clinical picture were examined
      with high-frequency ultrasound and native CT. The results of the examinations
      were compared with clinical data, surgical findings and histological evidence.
      Acute appendicitis was in 39 patients, other diseases of abdominal cavity and
      small pelvis--in 21. Sensitivity of CT was 95%, specificity--91.3%, accuracy-
      96.6%. Sensitivity of US was 92.3%, specificity--100%, accuracy--95%. The above
      parameters for non-invasive diagnostic methods were similar to ones for
      laparoscopy. Native CT and US are highly precise methods for diagnosis of acute
      appendicitis. They are preferable in unclear clinical situations, atypical
      location of the appendix, in children, elderly and aged patients, and in patients
      with mental disorders.

PMID- 12522921
TI  - [Prophylaxis and treatment of reflux cholangitis].
AB  - A method of creation of choledochojejunoanastomosis (CJA) was developed
      experimentally on 12 dogs. The method lies in creation of valvular CJA using
      walls of the common bile duct and submucosous-mucosous membrane of the small
      intestine mobilized by Roux. According to this method 103 patients with
      obstructive jaundice due to lesion of distal part of common bile duct were
      operated. Postoperative complications were seen in 6 (5.8%) patients, 3 (2.9%)
      patients died. In the period from 3 months to 10 years after operation 63
      patients were examined, there were no cases of reflux-esophangitis.

PMID- 12522922
TI  - [Enteral tube feeding early after surgery on the stomach and the duodenum].
AB  - Experience in enteral tube feeding (ETF) early after stomach resection,
      gastrectomy, reconstructive surgeries for chronic duodenal obstructions and
      postgastroresection disorders in 1716 patients is presented. Irrigators were
      installed in the jejunum during surgery, more rarely--through gastroscope below
      distal anastomosis. During the first day saline solutions were administered,
      further--nutritional cocktails. Period of ETF was 5.8 +/- 0.8 days in
      uncomplicated postoperative period and from 9 to 73 days in postoperative
      complications. ETF stimulates motor, resorption, synthetic, barrier functions of
      the small intestine. ETF permits to improve immediate results of stomach and
      duodenum surgery and to reduce cost of treatment.

PMID- 12522923
TI  - [One-stage esophagoplasty without transfusion of donor blood components].
AB  - Six patients aged from 27 to 62 years were operated for subtotal burn strictures,
      cancer and glandular polyp of a low-thoracic part of the esophagus using a
      complex program of non-blood surgery. The following methods were used: collection
      of autoplasma before surgery by plasmapheresis, collection of autologic packet
      red cells, normovolemic hemodilution during surgery, use of perftoran for oxygen
      transport and recombinant human erythropoetin to stimulate erythropoiesis and
      raise preporative level of hemoglobin. Components of donor blood were not used in
      these patients. There were no complications associated with these methods.
      Partial failure of esophagol-colonic anastomosis on the neck was seen in 1
      patient. The complex program permits one to avoid completely transfusion of donor
      blood components in esophagol surgery.

PMID- 12522924
TI  - [Influence of posttransplantation plasmapheresis on results of transplantation of
      a cadaveric kidney].
AB  - Plasmapheresis was performed with "Haemonetics" (USA), PCS-Ultralite and MCS+
      devices. During one procedure 1750-3550 ml of plasma were removed. Results were
      evaluated by the following parameters: diuresis within 24 hours after surgery,
      number of hemodialysis sessions after surgery, period of normalization of
      creatinine in blood. In patients of the study group oligoanuria was seen 4.5
      times more rarely than in the control group, they needed less sessions of
      hemodialysis. Level of creatinine normalized earlier in the study group. Actually
      survival of patients with potent transplants was higher in the study group than
      in the controls. It is concluded that plasmapheresis has positive influence on
      the course of posttransplantation period.

PMID- 12522925
TI  - [Pain syndrome after inguinal hernioplasty in an outpatient surgical facility].
AB  - Pain syndrome in 127 patients with primary inguinal hernia operated in surgical
      hospital and in 159 patients after similar surgery in outpatient setting with
      active movement postoperative regimen was studied. In the latter group relief of
      postoperative pain was associated with psychological preparation before and after
      surgery, surgical methods without tension of tissues, early physical activity of
      patients in postoperative period from the first hour. Absence of pain syndrome
      after surgery favors surgical treatment of inguinal hernias in one-day hospital.

PMID- 12522926
TI  - [Local sorption-detoxication therapy in combined treatment of acute purulent
      paraproctitis].
AB  - Efficacy of sorption-detoxication therapy (sorbent SUMS-1) in combined treatment
      of acute purulent paraproctitis was evaluated. Degree of endotoxication, state of
      postoperative wound, structural and morphological state of mucosous membrane of
      the rectum (light, electron microscopy, morphometry of biopsies) were studied. It
      was found that local use of sorbent increases efficacy of treatment of severe
      paraproctitis: endotoxicosis eliminates, regional hemo- and lympho-circulation
      improves, wound regeneration activates.

PMID- 12522927
TI  - [Omentoplasty in surgical treatment of osteomyelitis of the ribs and sternum].
AB  - Seven-year experience in the treatment of 21 patients with chronic osteomyelitis
      of the ribs and sternum is summarized. Great omentum was used as plastic and
      disinfecting material in combination with laser radiation. Indications,
      techniques, short- and long-term results are presented. There were no recurrences
      of purulent process in the bones. Omentoplasty is the method of choice in
      surgical treatment of purulent lesions of costal cartilage and sternum.

PMID- 12522928
TI  - [Antibacterial activity of imipenem/cilastatin (thienam) against agents causing
      pyoseptic processes].

PMID- 12522929
TI  - [Acute duodenal obstruction in burn disease].

PMID- 12522930
TI  - [Principles of analgesia in early postoperative period].

PMID- 12522931
TI  - [Diagnosis of abdominal injuries in combined trauma].

PMID- 12522932
TI  - [Cold injuries: actual problems of pathogenesis, diagnosis and treatment].

PMID- 12522933
TI  - [Methods of creation of intestinal anastomosis in colorectal surgery].

PMID- 12522934
TI  - [Health care services and regional development, a medicometric approach].
AB  - Health care services and regional development, a medicometric approach. If
      regional development is defined in terms of job creation and increased quality of
      life, health services can be seen as an investment contributing to employment and
      local structural changes. Spendings to increase health services, especially in
      peripherical regions, increase the level of economic development. Through case
      studies in Switzerland we open four perspectives for the future and propose a
      global view of health care systems in a regional context.

PMID- 12522935
TI  - [Multisystemic severe infection with Chlamydia pneumoniae].
AB  - Chlamydia pneumoniae (CP) is responsible for 8-10% of community acquired
      pneumonia. However, multiorgan disease is rare and the association with a
      cutaneous vasculitis has only been described once. We report a case of serious
      systemic CP infection with capillary leak syndrome and cutaneus vasculitis who
      was treated successfully with levofloxacin.

PMID- 12522936
TI  - [Traps of tuberculosis among the aged: an astonishing cyst of left foot].
AB  - We report the case of a 75 years old man who insidiously developed a unusual
      presentation of tuberculosis. The story began with a tuberculous arthritis of the
      foot, later associated with pulmonary, endobronchial, mediastinal and cervical
      lymphadenitis tuberculosis. Because the microscopic examination was negative for
      acid-fast bacilli (AFB) in all involved sites, the diagnosis of sarcoidosis was
      suggested. We discuss the diagnosis difficulties of tuberculosis in the elderly,
      the extrapulmonary manifestations of tuberculosis and some aspects of its
      differential diagnosis with sarcoidosis.

PMID- 12522937
TI  - [Pelvic and abdominal actinomycosis. Case report and review of the literature].
AB  - Pelvic and abdominal actinomycosis is a chronic suppurating granulomatosis caused
      by a Gram positive gem, Actinomyces Israelii. Manifestations of this rare disease
      may mimic cancer, inflammatory bowel disease, or diverticulitis. These syndromes
      lead to surgical exeresis. The diagnosis is obtained from the pathology report.
      We report the case of a 56 years old woman with large bowel obstruction secondary
      to extensive pelvic and abdominal actinomycosis. A review of the literature shows
      that the abdominal-pelvic form has been increasing over the past 10 years
      secondary to the increased and prolonged use of the intrauterine device.
      Treatment of this condition consists of a combination of antibiotics and surgery
      to achieve complete recovery.

PMID- 12522938
TI  - [One rare case report of acute renal insufficiency in rhabdomyolysis].
AB  - Mc Ardle's disease is a genetic glycogenosis characterized by the accumulation of
      glycogen in skeletal muscle secondary to the deficiency of muscle glycogen
      phosphorylase. The clinical consequences are an exercise intolerance with rapid
      muscle fatigue and muscle pain combined with a myoglobinuria. We report the
      medical story of a 45 years old man who suffers from Mc Ardle disease for ten
      years. He holds his family's doctor because of an oliguria and a weight gain of 5
      kg after one week of skiing and one afternoon of gardening. Moreover he complains
      of quadriceps muscle pains. His urine is orange-red. The supplementary
      examinations show a rhabdomyolysis and an acute renal failure. The patient
      benefits of a hemodialysis treatment with a progressive and complete recovery of
      his renal function after two weeks of treatment.

PMID- 12522939
TI  - [Primary pulmonary hypertension arterial and Basedow disease].
AB  - We report a case of a fifty year old woman with Graves' disease with positive
      AntiTPO antibodies and positive AntiTSH receptor antibodies, who was hospitalized
      with a right cardiac failure. A pulmonary hypertension was discovered on
      echocardiography. After adequate antithyroid therapy, the right cardiac failure
      regressed rapidly and pulmonary pressure normalised. An autoimmune process has
      often been proposed to explain the association between pulmonary hypertension and
      hyperthyroidism. We report the arguments supporting this autoimmune
      etiopathogenesis. We also discuss an other hypothesis based on a direct effect of
      thyroid hormones on the pulmonary circulation and the effects of high cardiac
      output associated with hyperthyroidism.

PMID- 12522940
TI  - [Infundibulitis, an unusual case of central diabetes insipidus].
AB  - We report the case of a 53 year old patient who was admitted with polyuria,
      polydipsia associated with fatigue, depression and sexual dysfunction. Central
      diabetes insipidus with hypogonadotrophic hypogonadism was diagnosed by a water
      restriction test and different static and dynamic hormonal dosages. Nodular
      thickening of the pituitary stalk was noted on the MRI and the biopsy permitted a
      histological diagnosis of infundibulitis.

PMID- 12522942
TI  - [Vertebroplasty and kyphoplasty:a review].
AB  - Only recently, vertebroplasty (VP) and kyphoplasty (KP) were introduced in the
      treatment of lesions of the vertebral body (VB). Most frequently, osteoporotic
      fractures (VP, KP) and metastases (VP) are treated in highly selected patients.
      These methods consist of polymethylmethacrylat (PMMA) injection into the VB
      usually through transpedicular canulas. In KP a coaxial balloon creates a cavity
      within the vertebral body, thus restoring some of the original VB height before
      cement injection. Consistently, these methods result in favourable outcomes.
      However, because of possible cement leakage and subsequent neurocompression with
      permanent damage, we advocate our surgical approach with prophylactic
      interlaminar fenestration prior to VP.

PMID- 12522941
TI  - [Sexual transmissible diseases and "returning leukorrhea"].
AB  - White discharges and sexual transmissive diseases are now increasing. Confronted
      to this symptom, the general practician can easily diagnose and treat his
      patient. Therefore he must keep in his mind that behind this common symptom, a
      much more serious disease can be hidden.

PMID- 12522943
TI  - [Evolution and surgical treatment of wrist sprains, 10 years of experience].
AB  - A retrospective study about 177 patients which were treated for dorsal ruptures
      of radiocarpal ligaments in 10 years allow to present a surgical procedure for
      treatment of sprain of wrist. It is a jacket plasty or an anchorage, effected for
      159 of all of them, after the lesion was made in evidence with the help of a
      selective compartimental arthrography. The recovery of the function of the wrist
      was obtained medially 10.7 weeks after the operation, without pain.

PMID- 12522944
TI  - [Proposal of a concept for the care of chronic wounds in hospitals in the Jura
      District].

PMID- 12522945
TI  - [Non-medical adventures in radiology].
AB  - Examples are presented of some unusual x-ray applications: not the one of daily
      diagnostics but the one of pure curiosity, revealing unexpected beauties of
      natural objects like shells and other treasures of the sea. The reason or their
      surprising esthetic impression is discussed by pointing out the predominant
      presence of symmetry in its various forms and combinations in the living nature.
      The role of the symmetry principle is discussed as an esthetic axioma as well as
      an essential condition of the evolution of species.

PMID- 12522946
TI  - State of the art treatment of the most difficult low density lipoprotein (LDL)
      cholesterol problems: LDL apheresis.
AB  - The patient benefit from reduction of an excessively elevated low density
      lipoprotein (LDL) cholesterol is now well established, especially when there is
      proven coronary atherosclerosis. Dietary adherence can lower LDL cholesterol by a
      maximum of 10% to 15%. The addition of a cholesterol-lowering medication
      frequently can achieve a major LDL cholesterol reduction. However, a small group
      of patients with a very high LDL cholesterol respond poorly to diet and
      pharmaceutical treatments. These same patients have the highest incidence for
      very premature coronary atherosclerosis and associated cardiac events. A few
      medical centers, including the University of Kentucky, have established a new
      program to benefit these difficult high-risk patients. The technique is known as
      LDL apheresis, an effective process for removal of LDL cholesterol. The procedure
      is highly effective but very costly and third-party approval barriers are
      preventing access to this essential treatment for some very high-risk coronary
      atherosclerosis patients.

PMID- 12522947
TI  - A doctor's prayer.

PMID- 12522948
TI  - Kentucky mammography availability.

PMID- 12522949
TI  - [Hygienic aspects of food safety in Russia: tasks and ways to accomplish them].
AB  - The article gives an account of the hygienic aspects of food safety of Russia,
      the questions of chemical and microbiological contamination of food products,
      vitamin and microelement deficiency in the diet of the population of this
      country. It outlines the ways of elimination of defects of the Russian
      population's diet.

PMID- 12522950
TI  - [The minimum foods basket and calculating the poverty level].
AB  - The principles of forming of the minimal food sets for the estimation of living
      wage is given in the historical perspective. The Russian food basket in 1999 is
      compared with those of FAO, USA and actual food consumption in low-income
      families.

PMID- 12522952
TI  - [The modern approaches to the complex treatment of functional constipation
      syndrome].
AB  - The high abundance of functional disorders of a gastrointestinal tract stipulates
      an urgency of studies dedicated to their complex treatment and preventenance. The
      complex treatment of functional snaps is necessary to base on the system of
      measures which are powering up medical power supply, a fissile way of life,
      recovering of regularity of the act of defecation, normalization of the emotional
      status of the patients. The article considers characteristics of different kinds
      of probiotical substances and factors which provide normalization of intestinal
      microbial balance and related to probiotical action.

PMID- 12522951
TI  - [Estimation of the allergenicity of specialized canned baby food made from fish,
      vegetables, and grains].
AB  - The influence of consumption of rations containing canned baby foods from mirror
      carp and Black Sea mullet on severity of system anaphylactic reaction to model
      food allergen in rats was studied and the level of antibodies to proteins of
      Black Sea mullet, mirror carp, Alaska Pollack, trout and big head was determined
      in serum of infants, suffering from food allergy through immune-enzyme analysis.

PMID- 12522953
TI  - [The comparative analysis of the glycemic effect of certain carbohydrate products
      on diseases of the biliary system].
AB  - A comparative analysis of glycemia effect of hydrocarbon foods in patients with
      dyskenisia of belieferous tract (n = 21), cholelithiasis (n = 20) and
      postcholecystectomy syndrome (n = 21). The food was given on an empty stomach on
      the basis of 50 g of carbohydrate per portion. The glucose level was defined in
      blood on an empty stomach and in 30, 60, 90 and 120 min. intervals after each
      loading. A significantly smaller increase of postfood glucemia after consumption
      of boiled rice and lentil was registered as well as accordingly low meanings of
      their glycemia indices in comparison with those of wheat bread and boiled
      potatoes.

PMID- 12522954
TI  - [The carbohydrate content of food products most widely used in the Russian
      population (bread, pasta, and baked goods].
AB  - The review of literature data on the structure of carbohydrates in local and
      imported bakery, macaroni and confectionary products is given. The role of
      separate components of carbohydrates in organism's vital activity is discussed.

PMID- 12522955
TI  - [Detection and serological screening of conditionally-pathogenic enterobacteria
      isolated from food products and the environment].
AB  - The spread of some coliform bacteria in foods, the faeces of children and adults
      and in human environment was studied, and the evaluation of their toxigenic
      potential and serological properties was given. More then 160 strains of
      enterobacteria including 70 strains of Escherichia spp were described. The
      frequency of detection enterotoxigenic E. coli in foods--18%--was approximately
      similar an amount of ETEC strains which was isolated in humans (22%). 3 strains
      of E. coli) 157 were found in foods and in clinical samples (1.9%). The observed
      results have confirmed the proposal about the increasing of ETEC E. coli food
      borne transmitting and dissemination its in the environment.

PMID- 12522956
TI  - [The effect of polar shark liver fat on the histology of rat internal organs].
AB  - One month keeping of rats on a diet with 23% fat extracted from a polar shark
      liver, causes not sharply pronounced fatty infiltration of liver, a moderate
      hyperplasia of spleen lymphoid tissue as well as its plasmatization and an
      increase of megakaryocytes, the predecessors of thrombocyte cells, in it.

PMID- 12522957
TI  - [Evaluation of the efficacy of biologically active dietary supplements in the
      diet therapy of patients with diabetes mellitus type II associated with obesity].
AB  - The dynamic of glycemia, insulin, C peptide, glycosylated hemoglobin,
      fructosamine, parameters of serum lipids, lipid peroxidation and system of
      antioxidant defense in 38 patients with diabetes mellitus type II associated with
      obesity was studied against hypocaloric diet No. 9 R. Besides favorable influence
      on a clinical picture of the diseas universal normalizing influence of
      hypoglycemic hypocaloric diet with food dietary supplement "Temarox" on
      parameters of carbohydrate, lipid and oxidative metabolism was disclosed. The
      scheme of investigation of efficacy of food dietary supplements in complex
      treatment of patients with diabetes mellitus type II associated with obesity was
      offered on basis of study of influence "Temarox" on mechanisms of metabolic
      disorders in these patients.

PMID- 12522958
TI  - [Evaluation of the effect of a medical-prophylactic product "Solnyshko" on the
      vitamin status in humans].
AB  - The results of use of a treatment-and-prophylactic product "Solnyshko" in
      people's food as well as pharmacological preparations containing b-carotene and
      ascorbic acid were submitted. It was shown that at the use of the specified
      product and pharmacological preparations there is an authentic improvement of b
      carotene and ascorbic acid supply.

PMID- 12522959
TI  - [Biochemical methods for evaluating the nutritional status of children].
AB  - As the total system of the children's nutritional status evaluation is the
      necessary part in the children's health guarding measures complex the
      significance of biochemical methods as the part of this system have been analyzed
      in the article. On the base of the literature data as well as on the authors own
      experience the classification of the existing biochemical methods for more than
      20 indices of children's nutritional status have been proposed. Advantages and
      disadvantages of the methods described have been briefly characterized.

PMID- 12522960
TI  - [Significance of recurring infections in biosafety].

PMID- 12522961
TI  - [Isolation of the West Nile fever virus from the great cormorant Phalacrocorax
      carbo, the crow Corvus corone, and Hyalomma marginatum ticks associated with them
      in natural and synanthroic biocenosis in the Volga delta (Astrakhan region,
      2001)].
AB  - Four strains identified as West Nile fever virus by inhibited hemagglutination
      and neutralization tests, enzyme immunoassay, and reverse transcription
      polymerase chain reaction were isolated during a virological examination of birds
      and their collected ticks in the natural and synanthropic biocenoses of the Volga
      delta. The strains were isolated from the great cormorant (Phalacrocorax carbo),
      the crow (Corvus corone) and its collected Hyalomma marginatum nymphs. The types
      of interpopulational relations in the ecological system wild-birds-virus
      mosquitoes-synanthroic birds-ticks are discussed.

PMID- 12522962
TI  - [Evaluation of the diagnostic efficacy of a test system for detecting hepatitis
      virus C RNA by polymerase chain reaction "AmpliSens(TM) HCV-240/BKO-440)"].
AB  - The test system developed at the Central Research Institute of Epidemiology,
      Ministry of Health of the Russian Federation for identification of hepatitis C
      virus RNA was studied. The sensitivity of the test system which the rate of
      similar results was 100% with its 5-fold reproduction was evaluated. That was 5 x
      103 genomic equivalents (or international units) per ml of a sample. A scheme for
      evaluation of the reproductibility of test systems based on the polymerase chain
      reaction (PCR) by using model samples is proposed. Whether it can be used for
      intra- and extra-laboratory assessment of the quality of PCR analyses is
      discussed.

PMID- 12522963
TI  - [Effect of heroin-containing substances on the infectivity of the human
      immunodeficiency virus type 1 in vitro].
AB  - At room temperature, HIV-1 IIIB is shown to remain infectious in a dose of 25
      mg/ml of heroin solution for more than 8 days. The large batch of HIV-1
      contaminated heroin solution may therefore remain infectious for a long period
      sufficient for transportation, packing, and sale in any area of Russia. At the
      same time 41-day incubation under the same conditions caused a complete loss of
      viral infectivity. Under certain conditions (the concentration of MT-4 cells
      being less than 2 x 105 cells/ml and the multiplicity of infection, less than
      0.01 ID50/cell), heroin was demonstrated to be able to increase HIV-1 replication
      at the early stages of its life cycle. The findings should be borne in mind in
      elaborating measures to prevent the spread of HIV-1 among intravenous
      psychoactive drug users.

PMID- 12522964
TI  - [Antineuraminidase activity of inactivated influenza vaccines in elderly people].
AB  - The antineuraminidase activity of 5 inactivated split and subunit influenza
      vaccines (IIV) was studied in individuals aged above 65 years. Postvaccinal
      antibody titers were determined in the lectin test. All the vaccines were shown
      to have a high antigenicity, by providing high titers of neuraminidase antibodies
      in most vaccinated persons: The mean geometric titers (MGT) to influenza viruses
      A(H1N1) and A(H3N2), and B were 7.4-8.0, 8.5-9.2, and 6.8-8.5 log2, respectively.
      Neuraminidases showed a higher activity in Vaxigrip-vaccinated persons in terms
      of both the rate of MGT increases and seroconversion that was 78-84%. The
      parameters of the anti-neuraminidase (anti-NA) and anti-hemagglutinating (anti
      HA) activities of IIV are summarized in the paper. There was a high coincidence
      of the results of both tests. At the same time it was shown that the postvaccinal
      humoral immune response might be directed only to one of the surface influenza
      virus proteins. The highest rate of seroconversions as to the surface antigens of
      all three influenza viruses was observed in Vaxigrip-vaccinated persons. The
      paper presents the results of comparison of the levels of MGT of antibodies to
      both viral surface proteins for all vaccinated with IIV, for those vaccinated who
      were infected during an epidemic season and a place group. The findings confirmed
      the value of higher titers of postvaccinal antibodies against influenza infection
      and illness.

PMID- 12522965
TI  - [Efficacy of amixine in experimental hantavirus infection].
AB  - The experimental studies conducted on 2-week suckling mice infected with Hantaan
      virus, Strain 76-118) treated with oral and subcutaneous amoxine showed its
      prophylactic, therapeutical-and-prophylactic, and therapeutical efficiencies.
      Oral amoxine exhibited the highest efficiency when used in a dose of 10 mg/kg-1
      96 hours before infection and throughout the incubation period. The protective
      efficiency was 61%. Subcutaneously, the agent was effective when three schemes
      for injection in a dose of 1 mg/kg-1. Its maximum effect was observed when
      amoxine was given by the therapeutical-and-prophylactic scheme. The death
      protection rate was 65%. The agent is effective in suppressing the reproduction
      of Hantaan virus in the brain tissue.

PMID- 12522966
TI  - [Effect of Ebola virus antigen on proliferative response of human lymphocytes in
      vitro: imbalance in production of tumor necrosis factor alpha and interleukin-1].
AB  - An in vitro model infection caused by Ebola virus (EV) showed a high production
      of tumor necrosis factor-alpha by human peripheral lymphocytes concurrently with
      a simultaneous reduction in the synthesis of interleukin-1 in response EV antigen
      stimulation. This may be an important factor in that VE suppresses the body's
      immunological resistance, which in turn causes unterferon deficiency and
      suppresses the formation of T helper cells.

PMID- 12522967
TI  - [Recombinant antibodies to tick-borne encephalitis virus].
AB  - A gene encoding the dimeric form of single-chain antibody fragments (scFv) was
      designed on the basis of the artificial gene coding monomeric scFv to tick-borne
      encephalitis glycoprotein E. The sequence encoding histidine oligomer was added
      to 3'-ends of the genes encoding the monomeric and dimeric forms of scFv
      antibodies. Escherichia coli strains were constructed for the production of
      monomeric and dimeric antibodies. These antibodies were purified using Ni-NTA
      resin. The specificity of the purified monomeric and dimeric antibodies in the
      binding reaction with tick-borne encephalitis virus was shown by ELISA and
      Western-blot analysis. The identity of glycoprotein E epitope bound by monomeric
      and dimeric scFv and parental monoclonal antibodies E6B was confirmed by
      competitive immunoassay.

PMID- 12522968
TI  - [Infection of mice with TT virus].
AB  - The sera pool of the human blood containing TTV DNA were administered to mice
      intravenously and then every 10 days examinations were made of blood serum and
      different organs of inoculated mice by polymerase chain reaction for presence of
      the viral nucleotide sequences. The viral DNA was revealed in the blood serum,
      the liver, kidneys and other organs 20 days after infection and persisted in most
      of the animals during 80 days. The data obtained show the possibility of TTV
      infection of mice.

PMID- 12522969
TI  - [Stability of hepatitis C virus RNA in human blood plasma in a panel of control
      samples].
AB  - The stability of hepatitis C virus (HPC) RNA concentration in 5 human plasma
      samples after storage at +22 degrees C for two months, at -20 degrees C, and +4
      degrees C for six months after 10 freezing-unfreezing cycles was evaluated. In
      this study, the concentration of HCV RNA in the samples was stable after six
      months of storage at -20 degrees C. The concentration of HCV RNA decreased on the
      average of 92% after 2-month storage at +22 degrees C. After six months of
      storage at +4 degrees C and after 10 freezing-unfreezing cycles, that decreased
      by 28 and 42%, respectively. Based on their own findings, the authors developed a
      HCV-RNA panel containing 5 positive human plasma samples with RNA levels of 103
      105 IU/ml. The panel may be recommended both for the standardization of PCR kits
      and for the intra- and interlaboratory quality control of PCR laboratories.

PMID- 12522970
TI  - [Assessment of a developed "nested" variant of polymerase chain reaction for
      detecting enteroviruses in patients].
AB  - The RT-PCR assay for the detection of all human enteroviruses was used to analyze
      fecal samples, cerebrospinal fluid (CSF), respiratory tract swabs, and sera from
      204 patients with symptoms of viral infection. Enteroviruses were detected in
      31.37% of cases. The proposed method analyzes every type of clinical samples. The
      relative detection rate of enteroviruses in different samples was 70.64% in
      feces, 10.4% in SCF, 17.24% in swabs, and 21.14% in the sera. The use of serum in
      addition to other testing samples increased the rate of enterovirus detection at
      18.25%. Developing techniques may be used for the diagnosis of acute enterovirus
      infections with different clinical manifestations.

PMID- 12522971
TI  - [Eradication of poliomyelitis and role of vaccine viruses in the process].

PMID- 12522972
TI  - Heart transplantation in Portugal: current status and future perspectives.
AB  - No other form of therapy, whether medical or surgical, has an impact comparable
      to heart transplantation on the quality of life and survival of selected patients
      with severe heart failure. In the EU and in the USA about 10 patients per million
      of population are transplanted each year. In Portugal, a country with a
      population of 10 million, 100 patients should be transplanted each year, but only
      12 patients were in fact transplanted in 1999. We rank 17th, in terms of the rate
      of heart transplantation per million of population, among the 23 European
      countries with registries of this activity. This is due to structural and
      organizational deficiencies of three main types: the lack of professional teams
      dedicated to severe heart failure treatment and heart transplantation; the lack
      of infrastructure, particularly heart failure wards and heart failure outpatient
      clinics; and the inappropriate distribution of the tasks associated with heart
      transplantation and patient follow-up. We present an estimate of the number of
      potential heart transplant candidates in Portugal, based on the EPICA study and a
      prediction of the resources needed for a successful heart transplantation program
      serving a population of 2 million. This was based on what is known of the natural
      history, morbidity and mortality of severe heart failure, on our own experience
      in this field, and finally on the experience of a large international heart
      transplantation center. The recommendations of the British Transplantation
      Society and those of the Department of Cardiothoracic Surgery of Stanford
      University were also taken into account.

PMID- 12522973
TI  - Effect of physical exercise on lipid metabolism in the elderly.
AB  - PURPOSE: To assess the effect of regular physical exercise on plasma lipids and
      apoproteins in an elderly group. MATERIAL AND METHODS: Sixty-three old people of
      both sexes, aged between 65 and 94, were randomly distributed between a test
      group (n = 31) and a control group (n = 32). The test group followed a program of
      physical exercise for eight months, with intensity of 60% to 80% of heart rate
      reserve, consisting of three weekly sessions, on alternate days, of 60 minutes
      each. Before the beginning of the program and eight months afterwards, blood
      samples were collected to assess total cholesterol, triglycerides, HDL-C, HDL2-C.
      HDL3-C, apo A1, apo B-100 and apo (a). The ratios total cholesterol/HDL-C, LDL
      C/HDL-C, HDL2-C/HDL3-C and apo A1/apo B-100 were also calculated. RESULTS: In the
      test group total cholesterol, triglycerides, LDL-C, apo B-100, total
      cholesterol/HDL-C and LDL-C/HDL-C decreased significantly; HDL-C, HDL2-C, apo A1,
      HDL2-C/HDL3-C and apo A1/apo B-100 increased significantly; HDL3-C and apo (a)
      did not change. The control group did not present any significant alterations in
      any of the parameters assessed. CONCLUSIONS: Regular physical exercise decreases
      vascular risk and may help to reduce cardiovascular events in the elderly.

PMID- 12522974
TI  - Inter-hospital transfer of critically-ill patients for urgent cardiac surgery
      after placement of an intra-aortic balloon pump.
AB  - METHODS: To assess the safety and feasibility of transfer of patients requiring
      urgent cardiac surgery, from a hospital without onsite cardiac surgical
      facilities, after insertion of an intra-aortic balloon pump (IABP) to maintain
      clinical and hemodynamic stability, a retrospective review of all cardiac
      charactheterizations was performed. Sixty-two patients required IABPs, among whom
      24 were transported to a surgical center from the outskirts of Lisbon to the city
      center in an ambulance accompanied by a physician, a nurse and paramedical
      personnel. RESULTS: Patients who required hemodynamic support with IABPs usually
      had unstable angina with critical coronary lesions requiring immediate surgical
      intervention, hypotensive patients with mechanical complications after an AMI,
      and patients with AMI who did not receive thrombolytic therapy, and with coronary
      lesions not amenable to percutaneous coronary intervention. All patients reached
      the surgical center alive, and no patient had either hemodynamic or electrical
      instability during transport. CONCLUSIONS: Surface transport of patients
      requiring emergency cardiac surgery after insertion of IABPs is safe, feasible
      and may provide circulatory and clinical stability in a subset of critically-ill
      patients.

PMID- 12522975
TI  - Atrial fibrillation and effective refractory period of the pulmonary vein ostia.
AB  - BACKGROUND: The pathogenesis of atrial fibrillation (AF) is not completely
      understood. The role of pulmonary veins (PV) in AF initiation is documented, and
      the recent demonstration of persistent fibrillatory activity in an isolated PV
      suggests that the PV play a role in the maintenance of AF. OBJECTIVE: Since AF is
      facilitated by multiple reentry circuits in atrial tissue with short effective
      refractory periods (ERP) and prolonged conduction times, we investigated whether
      PV have shorter ERP compared with the left atrium (LA). POPULATION AND METHODS:
      The study population consisted of five male patients, between 45 and 78 years of
      age, with normal sized LA; three had coronary artery bypass surgery (and no
      previous history of atrial arrhythmias) and two had paroxysmal lone AF refractory
      to antiarrhythmic drugs and were referred for percutaneous ablation with
      radiofrequency energy. In the surgical patients, epicardial bipolar pacing wires
      were inserted in the PV ostia and LA roof at the end of the procedure. Post
      operatively, the pacing wires were used to determine atrial thresholds and ERP in
      the PV ostia and LA roof. In the AF patients, atrial thresholds and ERP at these
      locations were obtained with the mapping/ablation catheter before and after PV
      isolation. ERP were determined with a basic pacing cycle length of 500 ms and a
      single extrastimulus with an initial coupling interval of 350 ms, gradually
      decreased (10 ms at a time) until atrial capture failure or AF induction.
      RESULTS: ERP in the LA roof were longer than 210 ms. The shortest ERP was always
      obtained in a PV ostium, with the shortest in the left PV ostia. The ERP values
      of the right inferior PV most resembled those of the LA roof. In patients
      referred for ablation, AF was induced when PV ostia with ERP shorter than 200 ms
      were stimulated. CONCLUSION: In the present study, the ERP of PV ostia were
      shorter than LA ERP, possibly explaining not only the presence of ectopic foci in
      the PV ostia, but also sustained fibrillatory activity in isolated PV, despite
      conversion of the atria to sinus rhythm. This fact may also explain the higher
      success rate and the preference for PV isolation in AF ablation.

PMID- 12522976
TI  - Atrial fibrillation: from mechanisms to curative therapy.

PMID- 12522977
TI  - Risk factors and clinical angiographical characteristics of myocardial infarction
      in women.
AB  - INTRODUCTION: Myocardial infarction has a higher incidence in men. However, in
      women, although less frequent, it has a worse prognosis. OBJECTIVE: With the
      present work we aim to define the clinical and angiographical characteristics and
      evolution of myocardial infarction in women compared with men. METHODOLOGY: We
      studied 235 sequential inpatients with acute myocardial infarction in the
      Intensive Care Unit who underwent post-infarction catheterization. We then
      compared female with male patients in terms of risk factors, location and type of
      infarction, coronary morphology and post-infarction complications. RESULTS: About
      22% of the patients hospitalized following myocardial infarction were female. The
      women were older than the men (65.9 +/- 11.2 vs. 60.3 +/- 11.9; p < 0.01), and
      had a higher prevalence of high blood pressure (71% vs. 54%, p < 0.05) and a
      lower prevalence of smoking (19% vs. 50%, p < 0.001). Post-infarction angina was
      more frequent in women (50% vs. 23%, p < 0.001). Neither Q-wave versus non-Q wave
      myocardial infarction nor its location were significantly different between the
      sexes. In terms of coronary morphology, myocardial infarction without significant
      lesions was more frequent in women (10% vs. 3%, p < 0.05) and there were no
      significant.

PMID- 12522978
TI  - Determinants of afterload-induced diastolic dysfunction.
AB  - Severe left ventricular (LV) afterload elevations induce diastolic dysfunction
      (DD). This decompensatory response, observed in both dogs and rabbits, seems to
      be related to cytosolic calcium levels. As rats have different calcium kinetics,
      we investigated the effects of acute LV afterload elevation in rats.
      Anaesthetized Wistar rats (n = 10) were instrumented in order to record
      simultaneously LV pressure and septal-free wall dimensions. Afterload was
      elevated through partial or total occlusions of the ascending aorta. In
      afterloaded heartbeats, we measured the time constant tau, the necessary (NTR)
      and the available (ATR) time intervals to complete LV relaxation. DD was
      evaluated through analysis of the position of the end-diastolic pressure-volume
      relation. Afterload elevations elicited acceleration of relaxation and DD was
      observed only in isovolumetric heartbeats. This DD could be explained by the
      deficit in time to complete relaxation in isovolumetric heartbeats. We conclude,
      therefore, that the time constant tau and ATR are the major determinants of
      afterload-induced DD. The calcium kinetics of the rat provide a better adaptation
      to afterload elevations in this than in other species.

PMID- 12522979
TI  - Fistula from the aortic sinus of Valsalva to the right ventricle--case report.
AB  - The authors report a case of a 42-year-old male, with the incidental finding of a
      fistula from the aortic root (sinus of Valsalva) to the right ventricle in the
      diagnostic work-up of atypical chest pain. The images and results of the exams
      are presented and the therapeutic options are discussed after the final
      diagnosis.

PMID- 12522980
TI  - Stress and cardiovascular disease.
AB  - After defining what cardiovascular disease is, the author describes the
      biological consequences of stress which are relevant to this kind of illness, the
      evidence for the relation between stress and cardiovascular disease, and
      predisposing factors (personality type, lifestyle, cardiac reactivity, working
      conditions, personal interaction and certain emotional states), and lastly
      provides a summary of explanatory mechanisms.

PMID- 12522981
TI  - Intention-to-treat analysis in clinical trials: principles and practical
      importance.
AB  - Intention-to-treat analysis is a technique used in randomized controlled trials
      (RCTs), where patients are compared--in terms of their final results--within the
      groups to which they were initially randomized, independently of receiving the
      allocated treatment, having dropped out of the study or having violated the
      initial protocol (for whatever reason). In other words, it constitutes an
      analysis of the results based on the treatment arm to which the patients belong
      due to the initial random allocation, and not on the treatment actually received
      (active or placebo). Intention-to-treat analysis permits the pragmatic evaluation
      of the benefit of a treatment change, and not the potential benefit in patients
      getting the pre-planned allocated treatment only. Full application of the
      intention-to-treat principle is only possible in those circumstances where all
      results from all patients are available. A significant number of RCTs state that
      they use intention-to-treat analysis, but the ways that violations of randomized
      allocation is handled varies considerably. Many trials present flaws in gathering
      primary data, and their methods of handling this problem are normally poor.
      Lastly, the intention-to-treat principle is frequently poorly described and
      applied. In this article we will present the importance, utilization, limitations
      and errors of intention-to-treat analysis.

PMID- 12522982
TI  - [Cardiovascular prevention: recommendations for approaching the vascular risk
      associated with dyslipidemia].

PMID- 12522983
TI  - Severe abdominal aorta hypoplasia in a child with Williams' syndrome.

PMID- 12522984
TI  - [There is a risk of reduced reliance of the public on vaccination programs. A new
      wave of infections can be the consequence].

PMID- 12522985
TI  - [The preventive instruments must be further developed. How do we affect the
      acceptance of preventive messages?].

PMID- 12522986
TI  - [Risk factors smoking, serum cholesterol and blood pressure analyzed. Excess risk
      also in the "moderate" groups].
AB  - Results of a prospective population study of a random sample of about 7,500 men
      aged 47-55 years at baseline and followed-up for 27 years are presented. All
      results are based upon the baseline examination. Among men who smoked 1-14
      cigarettes/day there were more events of lung cancer, myocardial infarction,
      stroke and all-cause mortality than in any of the other smoking categories. More
      events of myocardial infarction, stroke and all-cause mortality were found among
      men with serum cholesterol 6.00-6.99 mmol/L than among men with 7.00-7.99 and >
      or = 8.00 mmol/L. Similarly, more untoward events occurred in men with systolic
      blood pressures 140-159 mm Hg than in groups with higher levels. These results
      are due to the relatively low excess risk having been found among many
      individuals, giving rise to large effects in the population. They underscore the
      importance of avoidance of smoking even among those smoking "moderately", and to
      reduce cholesterol and blood pressure levels even among those with only
      moderately elevated levels. Non-pharmacological measures are indicated to reduce
      these levels.

PMID- 12522987
TI  - [Meeting women with chronic pain. "Health barometer" provides support for
      constructive dialogue].
AB  - The physician-patient encounter is time-constrained, and there may be little time
      to ask questions and identify problem areas in patients. Persons who experience
      aches, pains and other symptoms are sometimes confused in their crisis. The
      health barometer is a diagnostic aid that shows which areas to emphasize in the
      explorative conversation with patients. It is easy to use and it reflects the
      general, emotional, mental and social health of the patient when tested against
      the SF-36 health survey.

PMID- 12522988
TI  - [Peptides are opening the door for novel treatments of obesity and loss of
      appetite].
AB  - A wide spectrum of diseases, as well as states of attenuated ability to heal and
      recover, can be traced to over- or underweight. Patients at the extremes of the
      energy balance spectrum are becoming more and more common. In order to provide
      adequate care for such patients an understanding of the mechanisms governing
      feeding behaviour is required. In the last decade, important advances have been
      made in this direction, as several factors mediating signals of hunger and
      satiety to and within the brain have been identified. These factors include
      hormonal signals (such as leptin and insulin) from the energy stores as well as
      neuronal influences (via the vagus nerve) from the digestive tract. The
      information encoded therein is routed to specific nuclei of the hypothalamus and
      brain stem, respectively, leading to activation of complex neuronal networks
      spanning the most rostral regions of the brain all the way to the effector
      neurones of the autonomic nervous system located in the spinal cord. Several
      recently characterized neuropeptides showing potent stimulation of appetite
      (neuropeptide Y, agouti gene-related peptide, orexin, melanin-concentrating
      hormone) and satiety (melanocortins, cholecystokinin, cocaine- and amphetamine
      regulated transcript) have been localized to these pathways. These peptides, and
      the mechanisms through which they operate, offer promise for new therapeutic
      strategies in the treatment of obesity and anorexia.

PMID- 12522989
TI  - [Important steps towards the understanding of aging mechanisms].

PMID- 12522990
TI  - [Widely spread prejudice against obese persons].

PMID- 12522991
TI  - [The chairman of the drug committees: limit the reporting requirement between
      pharmacy and the prescribing physician concerning generic drug exchange].

PMID- 12522992
TI  - [Bone density measurement in heel bone is relevant for clinical care of
      osteoporosis].

PMID- 12522993
TI  - [Stillbirth: Better to improve the care than to put the clock back].

PMID- 12522994
TI  - [Apropos bone density measurement--"why to treat when it's possible to
      investigate?"].

PMID- 12522995
TI  - [News from the progress of quality indicators].

PMID- 12522996
TI  - [Should it be possible to search original preparations via pharmacies'
      computers?].

PMID- 12522997
TI  - [Why are old people not allowed to die with dignity?].

PMID- 12522998
TI  - [Apropos evidence-based lemons].

PMID- 12522999
TI  - ["Healed" appendicitis is more common finding at autopsy than surgically removed
      appendix].

PMID- 12523000
TI  - [Weighing of newborn infants--to be on the safe side?].

PMID- 12523001
TI  - [Treatment of children with hereditary and acquired brain damage. Is the Doman
      method justified?].

PMID- 12523002
TI  - [The possibility of discovering congenital defects before birth by means of
      prenatal ultrasound screening].
AB  - Ultrasound examination during pregnancy is now an essential part of modern
      obstetrical management. In many European countries women are offered 1-3
      ultrasound examinations during their pregnancy. In Denmark a similar offer is
      available but only to a very limited extent. Ultrasound examinations are
      performed on medical reasons. Modern equipment, trained sonographers, and the
      increasing use of ultrasound scannings imply that a considerable number of fetal
      malformations are diagnosed. A very comprehensive literature is available
      describing the sensitivity of diagnosing a fetal malformation at different times
      during the pregnancy. In a number of studies the sensitivity within different
      organ systems has been given as well. Intrauterine treatment is afield with great
      development, in which the more invasive operative techniques are replaced by
      laparoscopic procedures.

PMID- 12523003
TI  - [Screening of newborns for inborn errors of metabolism by tandem mass
      spectrometry].
AB  - Tandem mass spectrometry is an analytical method which is being implemented for
      neonatal screening. The method can determine the content of amino acids and
      acylcarnitines in neonatal screening samples in one integrated analysis. This
      allows detection of more than 20 inherited disorders of amino acid, fatty acid
      and organic acid metabolism. The aggregate incidence of these disorders is in the
      order of 1:4000. The principal disease which is detectable is medium-chain acyl
      CoA dehydrogenase deficiency, which has an incidence of 1:10,000-1:20,000 in
      Northern Europe. Medium-chain acyl-CoA dehydrogenase deficiency puts the affected
      at risk of life-threatening metabolic crises, which are preventable if the
      condition has been diagnosed. Hence, the prognosis is excellent. The central
      theme for therapeutic management of medium-chain acyl-CoA dehydrogenase
      deficiency is carbohydrate supplementation, especially in situations of
      intercurrent illness. Tandem mass spectrometry screening will also enhance the
      present screening for phenylketonuria which employs a bacterial assay: the
      screening sample can be obtained 48-72 hours post partum, the false-positive rate
      will be reduced, and there will be no interference with antibiotics. Tandem mass
      spectrometry is being used in state-mandated screening panels in a few places and
      is being tested in pilot studies in many other places. A national prospective
      pilot project was launched on February 1, 2002 in Denmark. The project includes
      tandem mass spectrometry screening for galactosemia. In addition to neonatal
      screening, tandem mass spectrometry can be used for investigation of metabolic
      diseases, sudden unexpected death of infancy and shaken baby syndrome. Critical
      appraisal of tandem mass spectrometry will lead to improved health for infants
      affected by rare inherited disorders of metabolism.

PMID- 12523004
TI  - [Diagnosis and acute treatment of inborn metabolic diseases in infants].
AB  - Inborn errors of metabolism are inherited defects in human metabolism. Many
      different metabolic diseases are known and, even though individually rare,
      collectively they are common and may appear in any pediatric department from time
      to time. To improve the prognosis for metabolic diseases, early recognition is
      necessary. Many infants with metabolic diseases can be diagnosed with routine
      biochemical tests and metabolic screening of urine. For some metabolic diseases,
      an early diagnosis will lead to specific treatment and improved prognosis, for
      others to genetic counseling and prenatal diagnosis. To achieve this it is
      important to think metabolic and screen for metabolic diseases when examining for
      sepsis. The article reviews the principles of early diagnosis and treatment of
      metabolic diseases in the first year of life.

PMID- 12523005
TI  - [Treatment of inborn metabolic disorders].
AB  - Biochemical knowledge about inborn errors of metabolism has increased
      considerably and new biochemical technology has improved our diagnostic
      possibilities. Therapy includes diet with substrate restriction and
      supplementation of deficient metabolites, medical reduction of substrate,
      inhibition of catabolic pathways, vitamins, enzyme substitution, enzyme
      stabilisation, and transplantation. A future possibility is somatic gene therapy.
      Treatment of many metabolic disorders is now possible, but it is important to
      establish both national and international expertise for proper use of new
      therapies and their evaluation.

PMID- 12523006
TI  - [Respiratory syncytial virus].
AB  - Respiratory syncytial virus (RSV) is the most common pathogen of the lower
      respiratory tract in infants. Groups at risk for severe disease include preterm
      infants, infants with pulmonary disease such as bronchopulmonary dysplasia,
      infants with congenital heart disease, and infants suffering from
      immunodeficiency. However, most infants getting severely ill from RSV are
      otherwise healthy and born at term. The incidence of hospitalisation caused by
      RSV is increasing, and there is an association between diagnosed RSV infection
      and subsequent development of wheeze and asthma. No vaccine or causal therapy is
      available. However, prophylaxis with a humanized monoclonal antibody of murine
      origin, palivizumab, reduces the risk of hospitalisation in high-risk infants,
      but the treatment is expensive. The most important prophylaxis methods at the
      present time are therefore hygienic measures with the purpose of preventing
      nosocomial infection in hospitals.

PMID- 12523007
TI  - [Prevention and management of pain in newborn infants. International consensus
      report].

PMID- 12523008
TI  - [Psychosomatic failure-to-thrive in infants and toddlers].
AB  - Failure to thrive is found in 3-5% of infants in the general population. A
      minority has an organic explanation. Non-organic failure to thrive is associated
      with increased risk of physical illness, continued growth retardation as well as
      cognitive and emotional disturbances. Non-organic failure to thrive has
      traditionally been regarded as a maternal deprivation syndrome, but in recent
      population studies there has been found no evidence of mother-infant relationship
      disturbances as the main cause of non-organic failure to thrive is the general
      population. Non-organic failure to thrive is best characterised as a
      psychosomatic condition with multifactorial etiology. Development and course of
      failure to thrive has to be explored in longitudinal population studies with
      prospectively gathered data concerning the perinatal period and first year of
      life.

PMID- 12523009
TI  - [Acute respiratory tract infections and mannose-binding lectin insufficiency in
      small children].
AB  - INTRODUCTION: According to hospital-based studies, increased susceptibility to
      certain infections is associated with genotypes that cause low serum levels of
      the protein mannose-binding lectin (MBL). However, the contribution of MBL
      insufficiency to the incidence of common childhood infections on a population
      basis is unknown. To investigate the effect of MBL insufficiency on the risk of
      acute respiratory infections (ARI) in unselected children, we performed a
      prospective population-based study of ARI in young children in Sisimiut,
      Greenland. MATERIAL AND METHODS: An open cohort of children aged 0-2 years was
      formed in 1996, and followed up with weekly morbidity surveillance visits for a
      two-year period. Episodes of ARI were diagnosed on medical history and clinical
      examinations. MBL genotypes were determined from blood samples according to the
      presence of structural alleles and promoter alleles. RESULTS: Altogether 294
      children participated and 44 refused. Blood samples were taken from 252
      participants. A 2.1-fold (95% confidence interval 1.4-3.1) increased risk of ARI
      was found in MBL-insufficient children compared with MBL-sufficient children (p <
      0.001). The risk association was largely restricted to the period 6 to 17 months
      of age, whereas less or no effect could be shown in younger and older children.
      DISCUSSION: These population-based data suggest that genetic factors such as MBL
      insufficiency play an important role in host defence, particularly during the
      vulnerable period of infancy between 6 and 17 months of age, when the adaptive
      immune system is immature.

PMID- 12523011
TI  - [Morbidity of Danish infants during their first months of life. Incidence and
      risk factors].
AB  - INTRODUCTION: The purpose of the study was to describe accumulated incidences of
      common diseases among Danish children during their first months of life, and
      identify risks and protective factors. MATERIAL AND METHODS: In 1995, mothers
      with Danish citizenship of 5998 randomly selected newborn children in Denmark
      were asked to participate in a national prospective study, representative of
      children of mothers with Danish citizenship. Mothers of 5429 infants participated
      and were interviewed when on an average their babies were 4 1/2 months old.
      RESULTS: At the time of the interview, 85% of all infants had had a cold, 23% had
      been wheezing, 22% had had rash/eczema, 13% had had vomits, 11% had had
      diarrhoea, 11% had had high fever without other symptoms, 5% had suffered from
      middle ear infection, 5% had had pneumonia, 1% had had blood in stools and 1% had
      had convulsions, and 13% had suffered from other diseases. Maternal age and
      breastfeeding protected against diseases. Siblings, damp/cold housing, and the
      psychological stress of the mother increased the risks, whereas maternal smoking
      and low birth weight had no effect on most of the outcomes. DISCUSSION: This
      study underpins the significant importance of breastfeeding against morbidity and
      the augmented risks from siblings.

PMID- 12523010
TI  - [Survival of children born with cerebral palsy. Children born 1971-1986].
AB  - INTRODUCTION: Since 1967, children with cerebral palsy in Eastern Denmark have
      been registered in the Danish Cerebral Palsy Registry. We wanted to investigate
      the survival of Danish patients with cerebral palsy and examine different factors
      that influence on survival. We also compared the survival rate with that of the
      background population. MATERIAL AND METHODS: All patients in the Cerebral Palsy
      Register, born between 1971 and 1986, were included in our study cohort. We
      examined the influence of the following factors on the survival of persons with
      cerebral palsy: sex, epilepsy, type of cerebral palsy, mental retardation,
      functional disability, birth year, and birth weight. Each factor was tested with
      Cox regression. RESULTS: Seventy-seven of the 1093 persons included (7%), died
      before September 1997. Our study showed that survival was associated with the
      type of cerebral palsy, epilepsy, mental retardation, and the degree of
      functional disability. Surprisingly, birth year and birth weight had no influence
      on survival. Persons with cerebral palsy had a lower survival rate than the
      background population. However, there was no significant difference between
      cerebral palsy persons with walking abilities, and the background population.
      DISCUSSION: Compared to earlier studies, the survival rate seems to have
      improved. The Danish cerebral palsy patients had a survival as good as, and maybe
      even better, than that of cerebral palsy patients from other countries. Persons
      with low functional disabilities had a survival rate comparable to that of the
      background population, a finding that may be relevant in regard to life
      insurance.

PMID- 12523012
TI  - [Morbidity among infants from ethnic minorities].
AB  - INTRODUCTION: The purpose of the study was to describe morbidity in ethnic
      minority children during their first year of life. MATERIAL AND METHODS: Baseline
      data from a cohort of 482 ethnic minority children born in Denmark in 1995. The
      mothers were interviewed in their homes, when on an average their children were 7
      1/2 months old. The results were compared with those of a parallel cohort study
      of 5429 children born in 1995 by Danish citizens. RESULTS: Out of all of the
      minority children, 86% had had a cold, 33% had had vomits, 29% had had diarrhea,
      27% had had fever without other symptoms, 21% had suffered from middle ear
      infection, 21% had been wheezing, 21% had had eczema/rash, and 10% had suffered
      from pneumonia. Minority children aged 3-6 months had more often had
      gastrointestinal symptoms, middle ear infection, high fever without other
      symptoms and had because of illness more often been seen by a family doctor, an
      emergency doctor or had visited an emergency room than was the case with Danish
      children. Minority children had more seldom than Danish children been ill or had
      a cold or wheeze, and had more seldom been given medication. DISCUSSION: Slightly
      increased morbidity from some illnesses was found among minority children and a
      little less from other illnesses compared with Danish children. However, the
      differences were not substantial.

PMID- 12523013
TI  - [Failure to thrive among hospitalized 0-2 year-old children].
AB  - INTRODUCTION: Failure to thrive, defined as insufficient weight gain according to
      age, is a well-known condition among infants and toddlers. The aim of the study
      was to investigate the prevalence of diagnosed failure to thrive and possible
      comorbidity in hospitalised 0-2 year-old children in the County of Copenhagen.
      MATERIAL AND METHODS: It resulted from inquiries sent to all paediatric
      departments in Denmark that the most frequently used ICD-10 diagnoses for failure
      to thrive were R62.8, E64.9, and E34.3. Data concerning patients with these three
      diagnoses hospitalised in two paediatric departments in the County of Copenhagen
      during a two-year period were drawn from the Patient Registry System. The
      following parameters were registered: sex, age, diagnoses, hospitalizations, and
      address. RESULTS: Among referred children below the age of two years, 173 or 4%
      were diagnosed with failure to thrive. Girls were in excess, the ratio girls-boys
      being 107:66. More than half, 60% were below one year of age, 40% were below six
      months of age. We found equal distribution of index children from municipalities
      with low and high incomes. The diagnosis R62.8 was found in 170 patients, of whom
      155 had the diagnosis as either main diagnosis or side diagnosis. Out of these
      155 patients 46% had additional somatic diagnosis, whereas 5% had child
      psychiatric comorbidity. DISCUSSION: Failure to thrive was diagnosed in 4% of
      hospitalised children under two years of age. Nearly half of the children
      diagnosed with failure to thrive had a comorbid somatic diagnosis, whereas only a
      few was diagnosed with psychiatric or social disturbances.

PMID- 12523014
TI  - [Children aged 0-3 years referred to child psychiatric department. A descriptive
      epidemiological study].
AB  - INTRODUCTION: In a Danish register study the incidence of children aged 0-3 years
      referred to child psychiatric services in Denmark increased by 30% during 1996
      1998. The objective of this study was to further describe 0-3 year-old children
      referred to child psychiatric departments with a view to distribution of
      diagnoses, age, sex, and parental mental illness. MATERIAL AND METHODS: Children
      0-3 years of age referred to child psychiatric departments in the County of
      Copenhagen in 1998 and 1999 were described on the basis of the clinical database
      and hospital records. RESULTS: A total of 159 children were admitted over a two
      year period corresponding to an incidence of 0.4%. The ratio boys: girls were
      1.3:1. However, with regard to pervasive developmental disorders boys dominated
      6:1. Among girls, eating disorders were dominating in the youngest children with
      ratio girls: boys 5:2. Pervasive developmental disorders were the most common
      diagnoses in children aged 2-3 years, and the overall incidence of this diagnosis
      was 0.25 per 1000 per year. The most common diagnosis of the youngest children
      was Z-diagnoses, and most often these children had mentally ill parents.
      Attachment disorders, eating disorders, and adjustment reactions were common
      diagnoses in children with mentally ill parents, but more than half of these
      children did not have any diagnosis at all. DISCUSSION: The incidence of children
      with pervasive developmental disorder was found twice as high as observed in a
      register study covering referrals of children aged 0-3 years from all psychiatric
      departments in Denmark during 1996-1998. Reactive attachment disorder, eating and
      adjustment disorder, and Z-diagnosis are the most common diagnoses in the
      youngest children, and most often these children have mentally ill parents.

PMID- 12523015
TI  - [Shaken baby syndrome--shaking violence against infants].
AB  - We describe two cases of shaken baby syndrome. Both children were about three
      months of age. It is important to recognise the characteristic features of this
      form of child abuse in order to prevent further damage and to ensure removal of
      the children from the abusive environment.

PMID- 12523016
TI  - [Hypernatremia in newborns].
AB  - Two cases of severe hypernatremia in healthy newborns are described. They were
      term infants with normal birthweight and breastfed at the discharge from the
      maternity ward. The infants had not been weighed from the time of birth until the
      day of admission to hospital at an age of seven and nine days. At the admission,
      the weight loss was 18% and 22% and the sodium concentrations were 160 and 164
      mmol/l. After rehydration mainly orally they were discharged bottle-fed after
      five and eight days, respectively. None of the mothers were able to breast-feed
      their infants at the time of admission. To prevent breast-feeding malnutrition
      and hypernatremia it is recommended that all newborns are seen and weighed by a
      professional during the second half of their first week of life.

PMID- 12523017
TI  - [Violence against women: role of health services].

PMID- 12523018
TI  - [Do pediatricians put their fingerprints on the vaccination program in Denmark?].

PMID- 12523019
TI  - [Physicians with substance abuse under supervision].

PMID- 12523020
TI  - [HIV and pregnancy].

PMID- 12523021
TI  - [Vertical transmission of HIV-1].

PMID- 12523022
TI  - [Vertical transmission of HIV in Denmark].
AB  - INTRODUCTION: Vertical transmission of HIV can be reduced if the pregnant woman
      and new born child receive antiretroviral treatment. Delivery by caesarean
      section and avoidance of breast feeding further reduce vertical transmission. The
      aim of this study was to describe the treatment of HIV-positive pregnant women in
      Denmark and the risk of vertical transmission. MATERIAL AND METHODS: We
      retrospectively describe the risk of vertical transmission of HIV among HIV
      positive women giving birth in Denmark during the period, mid-1994 to February
      2000. RESULTS: Fifty children were born. One mother gave birth twice during the
      study period, and one had twins. Five (10%) children were infected. All five were
      born by vaginal delivery. Three of the five mothers and three of the children did
      not receive antiretroviral treatment. The remaining two mothers were only given
      intrapartum treatment. In none of the five mothers was the HIV-infection known
      until the time of delivery or later. Transmission of HIV did not occur in the 34
      mother-child pairs who received antepartum and intrapartum antiretroviral
      treatment, who had a caesarean delivery, who did not breast-feed, and whose
      children were given postpartum antiretroviral treatment. DISCUSSION: It is
      important to identify HIV-infection in pregnant women in order to provide the
      relevant treatment and prevent vertical transmission of HIV.

PMID- 12523023
TI  - [Condom effectiveness in reducing heterosexual HIV transmission].

PMID- 12523024
TI  - [Substance abuse by health personnel].
AB  - This paper is a review of the literature on health professionals with substance
      abuse and it deals with the epidemiology, treatment, and results. A similar study
      has been carried out on health professionals in Denmark. Very few data are
      available for this group. The prevalence of substance abuse in health personnel
      seems to be equal to that in the general population, and from these data it is
      estimated that 3300 doctors/nurses in Denmark have an active alcohol abuse
      whereas the prevalence of other drug abuse is not known. The National Board of
      Health receives 150 new cases a year, in which decisions about specific treatment
      are made. Not all these cases are about substance abuse. Today, no organised
      treatment is on offer to health personnel with substance abuse, and they are
      forced to find their own. Results from abroad indicate that treatment with some
      degree of monitoring gives better results for health personnel than no
      monitoring, perhaps because of the risk of losing their authorisation, which is
      the penalty in this group, if substance abuse continues. From the results of a
      Danish study, the treatment in Greater Copenhagen seems less effective than the
      treatment given abroad. It is, therefore, recommended that the treatment of
      health personnel should be centralised in three or four places in Denmark, each
      with capacity for 30 outpatients. It is furthermore recommended that inpatient
      treatment of health personnel in work, which, generally speaking will be that
      needed in connection with detoxification, takes place in departments with a
      special interest in treating this kind of patient. Inpatient treatment is
      furthermore recommended for patients with psychiatric or somatic co-morbidity in
      addition to the substance abuse, or where repeated attempts at outpatient
      treatment have been unsuccessful. The estimated need is the possibility of
      admittance to two psychiatric beds per centre. Lastly, it is recommended that
      structured treatment in this group of patients should be established in close co
      operation with the unions for advisory or legal assistance in the case of early
      retirement or change of job.

PMID- 12523025
TI  - [Physicians and nurses subjected to disciplinary actions because of substance
      abuse. Ten years of experience with supervision in Copenhagen].
AB  - INTRODUCTION: Medical Health Officers supervise medical staff on behalf of the
      Danish National Board of Health. The Board can impose disciplinary action on
      registered providers of health care. MATERIAL AND METHODS: This retrospective
      investigation was based on case reports from 1 January 1989 to 31 December 1995
      on medical staff under individual supervision because of alcohol or drug abuse,
      with a 3-year follow-up to 31 December 1998 in Greater Copenhagen (about 1.25
      million inhabitants). RESULTS: Altogether 173 health personnel were identified.
      Of these, 47 physicians and 91 nurses had disciplinary actions imposed on them
      because of abuse. In well over a third the abuse had lasted less than two years,
      whereas in a third it had lasted more than five years before admission to
      individual supervision. Half of both physicians and nurses had undergone
      psychiatric treatment before that time. Frequent disciplinary actions imposed
      were examination of urine passed without prior warning and controlled treatment
      of alcohol abuse. Difficulties in adhering to these conditions were found in one
      third to half of the cases. The Medical Health Officers notified the National
      Board of Health of breaches in 64%, often several times for each person. At the
      end of the follow-up period, 49% were still working. There was a statistically
      significant excess mortality in the group. Of the 26 dead, four had committed
      suicide and in a further 12 cases poisoning or abuse was a contributory cause of
      death. DISCUSSION: Earlier detection, a tightening of sanctions, and improved
      treatment are recommended.

PMID- 12523026
TI  - [Chronic obstructive pulmonary disease. World COPD Day 2002].

PMID- 12523027
TI  - [Morbidity of infants born to diabetic mothers].
AB  - INTRODUCTION: The pregnancies of diabetic mothers, their deliveries, and
      complications in relation to the White class are well described. In contrast,
      very little is known about the morbidity of infants below one year of age, if
      their mothers suffer from diabetes mellitus. We examined this type of morbidity
      by analysing hospitalisation after the initial discharge, days with fever, number
      of contacts to their general practitioner, and increase in weight during the
      first year of life in relation to the maternal White class. MATERIAL AND METHODS:
      We carried out a questionnaire-based, follow-up study comprising 217 pregnant
      women with insulin-dependent diabetes mellitus, who were referred to Aarhus
      Kommune Hospital/Skejby Sygehus for pregnancy and birth care in the period 1985
      1995. RESULTS: We found that 20.3% of the infants had been hospitalised in the
      first year of life. There was a significant decrease in hospitalisation, fewer
      visits to the doctor, and fewer days with fever the higher the White class.
      Infants born of mothers belonging to White class B had the highest median birth
      weight. DISCUSSION: Infants who are delivered of mothers who suffer from severe
      diabetes have a similar rate of morbidity in their first year of life to children
      whose mothers only suffer from a mild type of diabetes.

PMID- 12523028
TI  - [The attitude of Arabic-speaking women to gynecological examinations].
AB  - BACKGROUND: The aim of the study was to describe and analyse the attitude of
      Arabic-speaking women to gynaecological examinations, with particular focus on
      the importance of the sex of the examining doctor. MATERIAL AND METHODS: Over a
      six-month period in 1998 all women of presumed Arabic origin were invited to
      participate in the investigation by referral to the Department of Gynaecology and
      Obstetrics at Odense University Hospital. An Arabic questionnaire was given to
      the participants and a Danish translation for second generation immigrants was
      also attached. RESULTS AND DISCUSSION: A total of one hundred questionnaires were
      collected. Of these about one third refused a gynaecological examination (GE) by
      a male doctor. Most gave their religion as the reason, whereas only a few refused
      the GE for personal reasons, and none claimed that their husband was the reason
      for their refusal. In half the cases, a female doctor was sent for. Many of the
      women who refused the GE by a male doctor were both educated and working, but
      their residence in Denmark was short. There was a connection between the refusal
      of the GE by a male doctor and the length of time the women had lived in Denmark.
      Most of those who were examined by a male doctor have lived in Denmark longer
      than those who refused the same GE.

PMID- 12523029
TI  - [Teenagers with asthma. A qualitative survey among teenagers with asthma of their
      expectations and attitudes when it comes to offered health care services].
AB  - INTRODUCTION: We wanted to examine the factors that were of importance for the
      hospital outpatient treatment of teenagers with asthma. MATERIAL AND METHODS: A
      total of 89 teenagers received a postal questionnaire and an invitation to
      participate in a focus group interview on outpatient asthma follow-up. RESULTS:
      Only 16 answered the questionnaire and 7 participated in the interview. The
      importance of personal contact was stressed and the teenagers expected much from
      the personnel aiming to help them. In a questionnaire follow-up of initial non
      responders, 82% still had asthma and 75% of these received asthma medication.
      DISCUSSION: The low participation rate and the high expectations explain why
      teenagers with asthma constitute a group of patients with less than optimal
      results of treatment.

PMID- 12523030
TI  - [HIV screening in pregnancy--too many failures?].
AB  - Danish official guidelines recommend that women belonging to risk groups should
      be offered HIV testing during pregnancy. Universal HIV testing during antenatal
      care is not required. We describe three infants with vertically acquired HIV
      infection born to mothers, who, despite belonging to high-risk groups (one from
      Thailand, two from Sub-Saharan Africa), had not been offered an HIV test during
      pregnancy. The infants, born within a one-year period, presented with AIDS
      defining symptoms during their first months of life. Two children had
      Pneumocystis carinii pneumonia and one had severe failure to thrive. These cases
      demonstrate that a significant number, perhaps up to 20% of women with known risk
      factors, are not HIV-tested during pregnancy. Thus, selective screening for HIV
      during pregnancy is ineffective and should be replaced by a universal offer of an
      HIV test.

PMID- 12523032
TI  - [Life-threatening subgaleal bleeding in a newborn infant].
AB  - Subgaleal haematoma, also called subaponeurotic haemorrhage, is a serious but
      rarely seen form of bleeding that can occur as a complication to vacuum-assisted
      delivery. Subgaleal haemorrhage may be much more copious than the more common
      subperiostal bleeding, and can almost exsanguinate the infant. A pressure bandage
      applied to the upper head can be lifesaving.

PMID- 12523031
TI  - [Stress hyperglycemia in a child with severe acute gastroenteritis].
AB  - A case of a two years and ten months old girl with severe acute gastroenteritis,
      dehydration, and hyperglycaemia is described. Transient hyperglycaemia is a
      common clinical finding in children under stress. We discuss the distinction
      between hyperglycaemia as a prediabetic state and that as a physiological
      response to stress during acute illness.

PMID- 12523033
TI  - [Picture of the month: hematoma of the nasal septum].

PMID- 12523034
TI  - [Use the concept "evidence" with care!].

PMID- 12523035
TI  - [Prenatal diagnosis].

PMID- 12523036
TI  - [Do yellow teeth become frail after hydrogen peroxide?].

PMID- 12523037
TI  - Blooming marvellous?

PMID- 12523038
TI  - Learning to listen.

PMID- 12523040
TI  - Using reflective writing to gain insight into practice with older people.

PMID- 12523039
TI  - Protecting older people from abuse.

PMID- 12523041
TI  - Managing Parkinson's disease in long-term care.
AB  - Parkinson's disease affects one in every 100 people over the age of 60 and one in
      ten nursing home residents. This article explores common problems associated with
      the disease and implications for nurses working with patients who display
      symptoms.

PMID- 12523042
TI  - Assessing fluid balance in older people: fluid needs.

PMID- 12523043
TI  - Measuring up.

PMID- 12523044
TI  - Fighting for a faculty.

PMID- 12523045
TI  - [Conjugated estrogen-gestagen does not reduce cardiovascular morbidity. Were
      these findings (in the Women's Health Initiative study) really unexpected?].

PMID- 12523046
TI  - [Research, progress and controversies around osteoarthritis].

PMID- 12523047
TI  - [Icelandic genealogical registry sheds light on the significance of heredity in
      osteoarthritis].
AB  - Osteoarthritis is a heterogeneous and multifactorial disease with many pathogenic
      mechanisms implicated in its development and progression. Although osteoarthritis
      is a manifestation of certain metabolic, mechanical or inflammatory events,
      several distinct forms of osteoarthritis are inherited as dominantly acquired
      Mendelian traits. Gathering evidence is showing that inheritance and possible
      mutations in genes associated with osteoarthritis can play a major role in the
      common form of osteoarthritis in many joints. By the introduction of new
      biological methods for finding gene defects the search for possible gene defects
      have taken mainly three forms: (1) Parametric linkage analysis of rare families
      in which osteoarthritis segregates as a Mendelian trait; (2) model free linkage
      analysis of affected sibling pairs, and (3) association analysis of known
      candidate genes. Mutations today known to be associated with osteoarthritis all
      occur in relatively rare syndromes or diseases, which have osteoarthritis as a
      major component. In recent years many loci have been found associated with the
      "common osteoarthritis phenotype". Chromosomes 2, 4, 6, 11 and 16 were identified
      in multiple genome scans and are therefore the most likely to encode
      susceptibility. Ongoing studies will lead to classifications of the "common
      osteoarthritis" based on the exact causative gene defects, rather than on their
      variable clinical and radiographic phenotype. Hopefully, these studies will lead
      to future new therapy of osteoarthritis.

PMID- 12523048
TI  - [No reduced number of abortions despite easily available emergency contraceptive
      pills. Studies of women's knowledge, attitudes and experience of the method].
AB  - Despite the fact that emergency contraceptive pills (ECP) have become easily
      available across the country during recent years, abortion numbers continue to
      rise in Sweden, especially in the young age groups (< 25). In a series of
      studies, we have investigated knowledge, attitudes and experience of ECP among
      young women. Our results show that, whereas most women are aware of the method,
      many lack knowledge about the mechanism of action and time frames for best use,
      which could explain why ECPs are not used by more than a fraction of women who
      might have had benefit from their use. Since half of the women requesting a
      termination of pregnancy stated that they would have used ECP if they had had
      them available at home at the time of the unprotected intercourse which led to an
      unintended pregnancy, it seems reasonable to encourage women to keep ECPs at
      home, in case the need should arise. It is important that ECPs are available
      without prescription, but beyond that, much more information about ECP is
      necessary in order for the method to be widely accepted and used as a back-up
      after failure with other contraceptives.

PMID- 12523049
TI  - [Salt, renal function and high blood pressure--reflections on a current issue].
AB  - The role of salt intake for blood pressure control has been discussed for a long
      time. A brief review is given of some pertinent physiological facts to explain
      this relationship and evolutionary aspects of renal function are emphasized. Salt
      intake is very high in the modern society, often as high as 15 g sodium chloride
      per 24 hours while 3-6 g may be more than enough to maintain an adequate salt
      balance. If the kidneys cannot cope with this severe sodium overload, blood
      pressure will rise. Therefore, the kidneys' ability to excrete sodium is a key
      factor and the salt excretion capacity is the kidneys' major barostatic function.
      As barostats, the kidneys control the blood pressure by ultimately determining
      the sodium excretion. Reducing sodium intake is, however, difficult as more than
      50% of the intake is contained in the food we buy such as bread, sausages, canned
      food, chips and fast-food. Food products should therefore be "salt declared", but
      information on this aspect is generally lacking. If the population's salt intake
      could be reduced by 50%, the prevalence of hypertension will be much reduced,
      perhaps also by as much as 50%. The cost to society for treating hypertension
      would be reduced accordingly. Salt intake is also an important aspect of the
      overweight problem among today's youth. Salt and overweight impose great health
      risks later in life. Preventive measures in this area must be given high priority
      in future health care work.

PMID- 12523050
TI  - [Mental illness as a public health problem is underrepresented in Swedish
      research. A survey of dissertations 2000-2001].

PMID- 12523051
TI  - [Focus on severe incidents in the new Lex Maria regulations].

PMID- 12523052
TI  - [Galenos--the most influential physician in medical history. Medicine for him was
      a universal science].

PMID- 12523053
TI  - [Current history of medicine is reflected by holistic ambitions].

PMID- 12523054
TI  - [A famous beauty was stricken with sinus thrombosis].

PMID- 12523055
TI  - ["Polypharmacy of today is not evidence-based!"University science is not always
      valid in a country cottage hospital].

PMID- 12523056
TI  - [The National Board of Health and Welfare on specialist competence: We have to
      take greater responsibility if we want the description of aims to be respected].

PMID- 12523057
TI  - [Increasing number of allergies--abolish the specialty of allergy!].

PMID- 12523058
TI  - [Should health services work with risk factors of diseases?].

PMID- 12523059
TI  - [Thrombosis diagnostics--give exact information directly!].

PMID- 12523060
TI  - [Final reply to Bengt Bjorksten: Seriously about circumcision!].

PMID- 12523061
TI  - [Keep the specialist's examination on a voluntary basis!].

PMID- 12523062
TI  - [Treatment with estrogen].

PMID- 12523063
TI  - [Benefits of cytological thyroid gland examination using needle biopsy in chronic
      fatigue].

PMID- 12523064
TI  - [P C Jersild on medical ethics: "It happens that I question my own point of
      view"].

PMID- 12523065
TI  - [Video capsule--a promising "bean"].

PMID- 12523066
TI  - ["Good advice" to travellers abroad is often of doubtful value. Personnel in
      charge of communicable disease control should act for a nation-wide harmony of
      risk assessment].

PMID- 12523067
TI  - [Charles XII seems to have fulfilled all the criteria of Asperger syndrome].

PMID- 12523068
TI  - [Location of the annual meeting of the Swedish Medical Society will also in
      future alternate between Stockholm and "other locality". The topic this year is
      "Emergency treatment"].

PMID- 12523069
TI  - [The enteroscopy capsule--a swallowable instrument for video examination of the
      small bowel].
AB  - Since 1.5 years wireless enteroscopy with the GivenM2A-capsule has been tested
      clinically. Wireless capsule-enteroscopy (WCE) has already contributed
      significantly to the understanding of patients with obscure intestinal symptoms.
      Series of occult bleeders show that WCE detects lesions in 60%, whereas
      enterography only in 15%, and push-enteroscopy in 25%. Lesions detected are
      angiodysplasia in 55%, ulcerations in 14%, apthoid lesions and erosions in 11%,
      tumours in 8%. Active bleeding was seen in 43%. In patients with Crohn's disease
      further information on extent of disease and type of lesions is gained, mainly
      seen as erosions in 64%. WCE in hereditary polyposis disclosed more and bigger
      lesions, and in celiac enteropathy villous atrophy and scalloping of the mucous
      membrane is readily identified. Software to locate the capsule in the
      gastrointestinal tract is recently launched together with a graphic display of
      capsule track and transit times. Soon displays for motility and pressure will
      follow. Capsule adaptation for screening for Barrett's esophagus and colon cancer
      might come true.

PMID- 12523070
TI  - [Chest pain unit--viable option when risk of cardiac etiology is modest.
      Multitudinous patient population brought together for structured survey and care
      at appropriate level].
AB  - Chest pain is a common reason for visiting emergency wards. It is often difficult
      to confirm or exclude ischemic heart disease even without objective signs and
      atypical symptoms. These patients are usually admitted to the hospital for a
      variable number of days and the investigational plan can vary even in the same
      hospital. We have opened a protocol-ruled chest pain unit for these low risk
      patients. Biochemical markers are analysed on point of care instruments at
      admittance and after four and ten hours. Continuous ST-analysis is available. An
      exercise test is performed after ten hours. During the first year 1424 patients
      were admitted and spent in median 24 hours at the unit. The main diagnosis at
      discharge were unspecified chest pain in 36% of the patients, ischemic heart
      disease (35%) and an other diagnosis (29%).

PMID- 12523071
TI  - [Chlamydia-like symptoms can have another etiology. Mycoplasma genitalium--an
      important and common sexually transmitted disease].
AB  - The aetiological importance of Chlamydia (C.) trachomatis in non-gonococcal
      urethritis (NGU) is undisputed. Mycoplasma (M.) genitalium has been shown to be
      strongly associated with NGU and with mucopurulent cervicitis and also with acute
      endometritis independent of C. trachomatis. In this prevalence study we examined
      946 patients, 445 women and 501 men, attending the STD clinic, for M. genitalium
      as well as C. trachomatis and Neisseria gonorrhoeae. M. genitalium was detected
      in urethral samples from 17 (13.4 per cent) of 127 men with both symptoms and
      signs of urethritis and from 2 (1.3 per cent) of 160 men without (p < 0.001).
      Corresponding figures for M. genitalium in the women were 15 (11 per cent) of 136
      women with symptoms and signs of urethritis or cervicitis compared to 3 (2.2 per
      cent) of 139 women without (p = 0.005). Examinations of partners of female and
      male index patients indicated that M. genitalium is sexually transmitted. Some M.
      genitalium infected patients had a history of irregular vaginal bleeding, lower
      genital tract pain, epididymitis and arthritis. Investigation of the aetiological
      role of M. genitalium in salpingitis, epididymitis and sexually acquired
      arthritis is urgently needed.

PMID- 12523072
TI  - [Increasing number of Chlamydia infections--how can we reverse this trend?].
AB  - The incidence of chlamydia in Goteborg, the second largest city in Sweden,
      increased by 81 percent between 1995 and 2001. The majority (82%) of men and
      women diagnosed with chlamydia were aged 15-29 years. The incidence of chlamydia
      was higher among teenagers from areas of lower socio-economic index during the
      first years of the study but after 1995 there was no difference between low and
      high socio-economic groups. Chlamydia tests were taken three times more often in
      women than men. Analysis of original data from the Swedish survey of sexual
      behaviour 1996 demonstrated a strong correlation between the number of sexual
      partners and STD. Strategies for preventing the spread of chlamydia should be to
      a greater extent directed towards men and include better accessibility for men to
      STD clinics as well as a general improvement in contact tracing. The general
      public should be informed about the fact that chlamydia infections do not always
      give symptoms and may lead to infertility. Campaigns about condom use in order to
      avoid chlamydia, HIV-infection and other STD are needed.

PMID- 12523073
TI  - [Who is to take overall responsibility for "travel medicine"? Amazingly deficient
      health control also of immigrants and asylum seekers].

PMID- 12523074
TI  - [Charles XII had all symptoms of Asperger syndrome: stubbornness, a stereotyped
      existence and lack of compassion].

PMID- 12523075
TI  - [Georgia O' Keeffe's art--expression of female sexuality].

PMID- 12523076
TI  - [Why are representatives of the Medical Society so afraid of the specialists'
      societies?].

PMID- 12523077
TI  - [Are physicians forbidden or obliged to influence medical priorities?].

PMID- 12523078
TI  - [Will primary health care live on prestige words?].

PMID- 12523079
TI  - [Complete and independent scrutiny of coxiber is required].

PMID- 12523080
TI  - [COX-2 inhibitors--actually, why to use them?].

PMID- 12523081
TI  - [A letter which will not change my prescribing patterns].

PMID- 12523082
TI  - [The desk of Virchow].

PMID- 12523083
TI  - [Assurance by the minister of health affairs].

PMID- 12523084
TI  - [Are too many antibiotics prescribed to Norwegian children?].

PMID- 12523085
TI  - [Drugs against the neglected diseases].

PMID- 12523086
TI  - [Outpatient laparoscopic fundoplication for gastroesophageal reflux disease].
AB  - BACKGROUND: Day-case laparoscopic fundoplication for gastro-oesophageal reflux
      disease was introduced in January 1997. MATERIAL AND METHODS: Inclusion criteria
      were ASA grade 1-2, living within 30 minutes by car from the hospital, or staying
      over in the patient hotel the first night, with company. Initially, only selected
      patients were offered day-case treatment; later it was adopted as routine. The
      patients underwent general intravenous anaesthesia with propofol and remifentanil
      and were given prophylaxis against postoperative pain and nausea. The surgical
      procedure was Nissen-Rossetti fundoplication or semifundoplication. RESULTS: 83
      patients were included. Ten patients were admitted, 73 (88%) were discharged as
      planned 3-8 hours after the operation. Eight patients (10%) were readmitted; one
      of them underwent reoperation for necrosis of the gastric fundus. Eight patients
      visited the outpatient department without need for readmission. At seven-day
      follow-up, 55 discharged patients (75%) were satisfied with the day-case
      treatment, nine (12%) were indifferent, and nine (12%) were dissatisfied, mostly
      because of pain. If offered a similar operation in the future, 50 patients (68%)
      would have preferred and 11 (15%) would have accepted day-case treatment; 12
      (16%) would not. INTERPRETATION: Outpatient laparoscopic fundoplication is safe
      and well tolerated by the majority of patients.

PMID- 12523087
TI  - [Appendicostomy for fecal incontinence in children and young people with
      myelomeningocele].
AB  - BACKGROUND: Myelomeningocele is a congenital condition where the central nervous
      system is affected; it may cause paresis in the bladder, colon and lower
      extremities. For the patients, faecal incontinence and obstipation are
      troublesome problems that are difficult to treat successfully. MATERIAL AND
      METHODS: 13 persons were included in the study. Faecal incontinence was the main
      indication for appendicostomy for antegrade irrigation. Five patients underwent
      laparoscopic surgery, the rest had an open laparotomy. The appendix was pulled
      out and anastomosed to the skin. In that way it made a channel through which a
      catheter could be introduced. Water could be instilled and the bowel emptied by
      irrigation. RESULTS AND INTERPRETATION: No patient continued major soiling. Five
      leaked small quantities of faeces, in two there was some mucus discharge from the
      stoma, and one patient had problems with the irrigation. All patients were able
      to carry out the irrigation themselves, but a main problem was to motivate them
      to be responsible. This seemed to be correlated to the age of the child.
      Appendicostomy is therefore an effective method in the treatment of faecal
      soiling when all other conservative methods have failed.

PMID- 12523088
TI  - [Measurement of fever in children--is infrared tympanic thermometry reliable?].
AB  - BACKGROUND: Our objective was to determine whether infrared tympanic thermometry
      is as reliable as the rectal digital thermometer. Earlier reports have given
      conflicting results on the issue. MATERIAL AND METHODS: 199 children aged 1 month
      to 12 years were included in the study. Rectal temperature and the temperature in
      at least one ear were obtained from all of the children. Children with perforated
      otitis media, intracranial tumours or treated with immunosuppressive medication
      were excluded from the study. RESULTS: The mean temperature in the rectum was 0.4
      degree C higher than in the ear. The tympanic and the rectal readings were
      strongly correlated (r = 0.83, p = 0.01). With a definition of fever as rectal
      temperature > or = 38 degrees C the sensitivity of the tympanic thermometry was
      71%, the specificity 95%, the positive predictive value 93%, and the negative
      predictive value 78%. INTERPRETATION: Infrared tympanic thermometry has obvious
      advantages compared to rectal measurements: It is more hygienic, faster and less
      painful for the child. However, its sensitivity is rather low when used in an
      emergency department. This means that a number of children with fever will not be
      diagnosed as such.

PMID- 12523089
TI  - [The effect of patient education in asthma, a randomized controlled trial].
AB  - BACKGROUND: Our aim was to evaluate costs and consequences of patient education
      in asthmatics in a twelve-month follow-up. MATERIAL AND METHODS: 78 asthmatics
      were randomly allocated to a control or intervention group after having received
      ordinary outpatient care. Intervention consisted of two two-hour group sessions
      followed by one or two individual sessions administered by a nurse and a
      physiotherapist. Self-management was emphasised. Visits to the doctor, prescribed
      drugs, hospital admissions, travel costs, time costs, and educational costs were
      recorded. RESULTS: In a twelve-month follow-up, patient education resulted in
      approximately a 70% reduction in GP visits and days off work due to asthma as
      well roughly a doubling of proportions with satisfactory steroid inhaler
      compliance compared to no education. Patient education also improved lung
      function (FEV1) by 6%, and it improved quality of life. The control and
      intervention groups had mean total costs of NOK16,000 and 10,500 per patient
      respectively. A 5% improvement in FEV1 in the intervention group was associated
      with savings of NOK 4,500 compared to the control group. The number needed to
      educate (NNE) to make one person symptom free was associated with savings of NOK
      12,200. INTERPRETATION: Patient education in asthmatics in a twelve-month follow
      up improved patient outcomes and reduced costs.

PMID- 12523090
TI  - [Children in day care centers--infections and use of antibiotics].
AB  - BACKGROUND: Bacterial resistance is a major problem in many countries and is
      associated with liberal use of antibiotics. In this study infections and use of
      antibiotics were studied in day-care children in Oslo and Akershus counties in
      Norway. MATERIAL AND METHODS: Parents in 22 randomly chosen day-care centers were
      asked to complete a semi-structured questionnaire about infections and antibiotic
      treatment of their children over the last 12 months. Out of 1,126 parents, 563
      (50%) completed the questionnaire. RESULTS: 97% of the children had suffered
      infections over the last 12 months (mean seven infections); colds 85%, otitis
      36%, throat infections 27%, bronchitis 13%, pneumonia 12%, eye infections 41%,
      gastroenteritis 63%, and wound infections 9%. Out of 3,900 episodes of
      infections, 29% were treated with antibiotics; in all, 65% of the children
      received antibiotics. 80% of parents had consulted physicians with their
      children: 80% of the consultations resulted in prescriptions of antibiotics. Boys
      had more infections than girls and used antibiotics more often. Younger children
      had more infections than older ones, but did not use antibiotics more often.
      Among children with ear infections 75% got antibiotics, throat infections 85%,
      bronchitis 82%, and eye infections 58%. INTERPRETATION: Children in day-care
      centers in the Oslo area have a high occurrence of infections, a high rate of
      medical consultations, and a very high use of antibiotics.

PMID- 12523091
TI  - [Vaccination of immunocompromised patients].

PMID- 12523092
TI  - [Personal data used in medical research].

PMID- 12523093
TI  - [Exceptions when it comes to confidentiality in connection with certain research
      projects].

PMID- 12523094
TI  - [Health economics--short introduction to cost-benefit analyses].

PMID- 12523095
TI  - [New ways of specialist education in the USA].

PMID- 12523096
TI  - [Guidelines are based on subjective view and choice of values].

PMID- 12523097
TI  - [Treatment of patients with functional disorders].

PMID- 12523098
TI  - [Analysis of methanol "everybody" can perform--diagnostic help or ethical
      problem?].

PMID- 12523100
TI  - [The health does not know national borders].

PMID- 12523099
TI  - [Electronic medical record].

PMID- 12523101
TI  - [The Konrad Reijo Waara Award 2002 to Erik E. Anttinen--an advocate for patients'
      value and position].

PMID- 12523102
TI  - [The Duodecim Information Award to Mardy Lindqvist. A journalist is not a
      megaphone].

PMID- 12523103
TI  - [Nematode--the mother or father of programmed cell death].

PMID- 12523104
TI  - [Finnish hereditary neurological diseases as focus of the research].

PMID- 12523105
TI  - [Sentinel lymph node biopsy in patients with cutaneous melanoma].

PMID- 12523106
TI  - [Small intestines as an immunological organ].

PMID- 12523107
TI  - [Tyrosine kinase inhibitor as a targeted therapy for GIST tumors].

PMID- 12523108
TI  - [Pneumothorax and chest x-ray after ultrasonography-guided pleural puncture].

PMID- 12523109
TI  - [Large colorectal adenomas].

PMID- 12523110
TI  - [Respiratory arrests caused by congenital myasthenia gravis syndrome].

PMID- 12523111
TI  - [An elderly patient as a cancer patient].

PMID- 12523112
TI  - [Even the healthy ones are not totally perfect].

PMID- 12523113
TI  - [Evaluation of blood flow velocity and cerebrovascular reactivity in patient with
      posterior circulation stroke].
AB  - The aim of our study was to determine the type of blood flow disturbances and
      cerebrovascular reactivity of major anterior and posterior circulation cerebral
      vessels in patients with posterior stroke (POCI). The examined group consisted of
      17 patients, mean age 57 +/- 12 yr, with posterior circulation infarct.
      Neurological examination, brain CT and Doppler examination including evaluation
      of BFV and CVR of MCA, PCA and VA was performed in each patient. Doppler
      examination was done using Pioneer TC 2020 and capnograph Tidal Wave sp
      Novametrix. RESULTS: BFV of ICA's, MCA's, ACA's and PCA's were diminished while
      BFV of VA's were significantly diminished in the examined patients compared to
      healthy controls. CVR of MCA in posterior circulation stroke patients was
      significantly lower compared to controls. CVR of PCA and VA was significantly
      lower compared to CVR of MCA in patients with posterior circulation stroke.
      CONCLUSION: Impairment of CVR, especially in posterior circulation, plays an
      important role in posterior circulation stroke pathogenesis.

PMID- 12523114
TI  - [Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis patients
      with dysphagia. A preliminary report].
AB  - Percutaneous endoscopic gastrostomy (PEG) has been proposed as symptomatic
      treatment of dysphagia in amyotrophic lateral sclerosis (ALS) patients. The aim
      of our study was to assess the safety and complications and survival after PEG
      implantations in 13 ALS patients. We discuss the factors related to survival in
      two groups: dead (6 out of 13 patients) and alive (7 out of 13) after PEG
      implantations. We demonstrate that the PEG procedure is quite safe and forced
      vital capacity (FVC) is a major factor related to survival after PEG implantation
      in studied patients.

PMID- 12523115
TI  - [Clinical picture of patients with Huntington's disease in relation to the number
      of trinucleotide CAG repeats in IT-15 gene].
AB  - Huntington's disease (HD) is a neurological condition of progressive course that
      results from abnormally increased number of CAG repeats within IT-15 gene, coding
      for huntington. The main symptoms consist of choraetic movements, dementia, and
      characteropathy. The aim of the present study was to search for possible
      correlation between the age of the onset of HD, time from the onset, clinical
      status of the patients, and CAG repeats number. Ten patients were studied
      altogether. Modified UHDRS (MUHDRS) was applied for the estimation of patients'
      clinical status. The number of CAG repeats in examination of the IT-15 gene was
      determined by polymerase chain reaction (PCR) and separation of radioisotope
      labelled PCR product against DNA size marker in polyacrylamide gel. A negative
      significant correlation was found between the CAG repeats number and the disease
      onset age (r = -0.67; p < 0.05) and MUHDRS score (r = 0.75; p < 0.05), as well.
      Negative significant correlation between time from the onset and MUHDRS score (r
      = -0.95; p < 0.05) and negative correlation between summarised: time from the
      onset and CAG number on the one site and MUHDRS on the other (p = -0.91) were
      found, as well. Our findings indicate an interdependence between CAG repeats
      number within the IT-15 gene, the course of the disease and the clinical status
      of HD patients.

PMID- 12523116
TI  - [Spontaneous cerebellar haematomas--results of surgical treatment].
AB  - The authors analysed 21 patients with spontaneous cerebellar haematomas.
      Spontaneous cerebellar haematomas constitute 10% of all intracerebellar
      haematomas. Hypertension was the most frequent cause of haemorrhage (85.7%).
      Vascular malformation was disclosed only in 2 cases. All patients were treated
      surgically. External ventricular drainage was applied in 5 patients, in 7 cases
      the haematoma was removed and in 9 cases both methods were applied. The results
      of the treatment were evaluated with regard to: localization of the haematoma in
      the cerebellum, its volume, presence of the intraventricular haemorrhage and the
      hydrocephalus coexistence, the degree of visibility of the brainstem cisterns and
      the patient's state according to the GCS scale. The evaluation was the basis to
      formulate a 14-point scale which could be useful in patient's treatment and
      prognosis. [table: see text] The 1st degree patients should undergo conservative
      treatment, those classified as the 2nd degree patients could potentially undergo
      surgical treatment, and those who qualify as 3rd degree patients absolutely
      require surgical treatment.

PMID- 12523117
TI  - [Brachial plexus tumors--neurosurgical treatment].
AB  - Tumours of the brachial plexus according to present classification are included
      to soft tissue tumours. Because of rare occurrence of these tumours diagnostic
      and operative experience is relatively small. There is also a few number of
      publications regarding tumours of the brachial plexus. Therefore the aim of the
      study was to present our experience in the surgical treatment of tumours of the
      brachial plexus basing on the material of 5 cases treated in the years 1997-2001.
      There were 4 males and 1 female, age from 17 to 58 years old. Four patients were
      under 27 years old. In 3 cases tumours of the brachial plexus invaded the spinal
      canal through the intervertebral foramen and caused spinal cord compression (type
      A). In 2 cases tumours involved only plexus elements (type B). In 2 cases tumours
      were associated with neurofibromatosis type II. Five cases of neural sheath
      tumours included 2 schwannomas, 2 neurofibromas and 1 schwannoma malignum. All
      patients underwent surgery. In case of schwannomas and neurofibromas the surgical
      removal was radical without impairment of brachial plexus function. In case of a
      giant schwannoma malignum tumor, which caused flaccid paresis and symptoms of
      insufficient blood, supply with severe pain in the upper limb radical extirpation
      was also possible. In type A tumours in the first stage intraspinal part of the
      tumor was removed. Follow up observation lasted from 3 months to 4 years. The
      result of treatment of benign tumours was very good with complete function
      recovery of the upper limb, pain disappearance and no symptoms of recurrence in
      the long postoperative period. In case of malignant schwannoma in the early
      postoperative period both pain and symptoms of blood supply disturbances
      completely disappeared. The patient died 12 months after the operation because of
      tumor dissemination. Benign tumours of the brachial plexus can be effectively
      surgically treated using microsurgical techniques and, if necessary, nerve
      grafting. In case of malignant tumours many authors also recommend surgery with
      optimal sparing of the brachial plexus function and subsequent radio and
      chemotherapy. Low number A few cases in our series makes impossible to draw any
      epidemiological conclusions.

PMID- 12523118
TI  - [The effectiveness of microvascular decompression in various types of vascular
      compression in patients with trigeminal neuralgia].
AB  - The aim of the work was to evaluate the efficacy of microvascular decompression
      (MVD) in different types of vascular compression (VC) in 20 patients with the
      idiopathic form of trigeminal neuralgia (TN). The typical VC was found in 17
      cases. An arterial vessel was the cause of VC in 6 cases, a venous vessel in 5.
      The mixed type of VC was present in 6 cases. In every case of the mixed VC one of
      the vessels compressing the 5th nerve predominated: arterial in 5 and venous in
      1. In 3 cases of TN no VC was found. Observation time after MVD was from 6 to 61
      months (median 26.7 months). In the TN patients with the arterial VC (including
      the mixed VC with the arterial predominance) pain relief was complete in 7 cases,
      satisfactory in 2 and none in 1 case. In patients with venous VC (including mixed
      VC with venous predominance) pain relief was complete in 4 cases and satisfactory
      in 2. In the TN patients without VC pain relief was satisfactory in 1,
      unsatisfactory in 1 and none in 1 case. Long term results of MVD in the analyzed
      series of the TN patients confirm the efficacy of MVD when vascular compression
      of the 5th nerve--either arterial or venous--is found intraoperatively.

PMID- 12523119
TI  - [Neurodegeneration with brain iron accumulation, type-I (NBIA-I) (formerly
      Hallervorden-Spatz, disease). Par I: clinical manifestation and treatment].
AB  - This is a rare syndrome, most likely of several genetically determined
      neurodegenerative disorders with similar pathogenesis. Two forms of the disease
      are distinguished: familial occurring in about 50% of cases and sporadic with
      about 15% of cases in which parental consanguinity is found. Clinically, NBIA-1
      is characterised by a slow progression of extrapyramidal symptoms and progressive
      dementia, mostly in children. Relentlessly progressive course is obvious, but the
      progress may be very slow, taking sometimes several dozen of years. Four subtypes
      of the disease have been thus far distinguished: early childhood, late childhood,
      adult onset and with protracted course. The clinical diagnosis of NBIA-1 is only
      probable because specific abnormalities have not as yet been detected in
      laboratory investigations. However, NBIA-1 should be suspected, if extrapyramidal
      symptoms are observed, such as dystonia, choreoathetosis, muscular rigidity,
      moreover dementia, retinal degeneration and/or optic nerve atrophy and
      characteristic magnetic resonance imaging (so called "the eye-of-the tiger"
      sign). At present, only comprehensive symptomatic treatment is possible.

PMID- 12523120
TI  - [Whipple's disease--a rare cause of neurological symptoms and disorders].
AB  - Whipple's disease is a chronic infection caused by Gram-positive bacillus
      Thropheryma Whippelii picture with a wide range of clinical manifestation, not
      only systemic but also neurological. Seronegative arthritis or arthralgia may be
      the only presenting symptom, predating by years gastrointestinal, and also
      pulmonary, cardiac, renal and neurological manifestations. The diagnosis can be
      established based on the characteristic histopathological features found in the
      affected organ (foamy macrophages with a coarsely granular cytoplasm, which
      stains with PAS) and PCR of 16S ribosomal RNA of Tropheryma Whippelii. CNS
      involvement manifests with a broad range of neurological symptomatology: memory,
      consciousness, hypothalamic, psychiatric and behavioural disorders and other
      symptoms, which may mimic neurodegeneration, neuroinfection, stroke and tumour.
      In this review detailed neurological symptomatology, differential diagnosis and
      laboratory, neurophysiologic and radiologic findings are presented. Whipple's
      disease is potentially fatal but responds to antibiotic treatment. The current
      recommendations for treatment are discussed.

PMID- 12523121
TI  - [GABApentin--new therapeutic possibilities].
AB  - The paper is a review of current experience with use of gabapentin--a new
      antiepileptic drug--in neurologic conditions others than epilepsy. Mechanism of
      action of the drug is not fully elucidated yet. However it proved to be effective
      in therapy of chronic pain, especially in neuropathic pain, neuralgia, low back
      pain, reflex sympathetic dystrophy and erythromelalgia. Gabapentin is also
      effective in pain and spasticity in multiple sclerosis. Clinical studies of
      gabapentin in movement disorders, such as Parkinson disease, essential tremor and
      atrophic lateral sclerosis are discussed in the paper. It can be summarized that
      gabapentin is a valuable medication and the use thereof in neurology is not
      limited to epilepsy.

PMID- 12523122
TI  - [Glia-like brain tumors. Potential role of thyroid hormone and its nuclear
      receptors (TR)].
AB  - Over-proliferation of certain cells lead to tumor formation and therefore
      impairments of regulation of the cell cycle are inalienable and basic signs of
      neoplasms. The majority of known oncogenes and tumor suppressors are components
      of a few common signaling pathways that control the cell cycle, genome integrity,
      cell differentiation and apoptosis. Changes in these signaling pathways cause the
      development of tumor genesis. The thyroid hormones (3, 5, 3'-L-triiodothyronine,
      T3; 3, 5, 3', 5'-L tetraiodothyronine, T4; TH) play crucial roles in the growth
      and differentiation of many organs, including the central nervous system. TH
      exerts its major effect by binding to the nuclear TH receptor (TR). TR is bound
      to specific DNA sequences known as TH-response elements (TREs), composed of two
      half-site core motifs (AGGTCA), with specific nucleotide spacing and orientation.
      TR also bind to several coregulators such as corepressors and coactivators. The
      liganded complexes ultimately determines nuclear TH action. .

PMID- 12523123
TI  - [Cerebral venous thrombosis: a young woman case study].
AB  - Cerebral venous sinus thrombosis is a rare, serious cerebrovascular disease with
      poor prognosis. It can be a sequel to various coagulation disturbances, head
      injuries or local inflammations. We report a case of a young woman with no risk
      factors detected, who developed a massive cerebral venous sinus thrombosis. She
      had progressively worsening symptoms, including left hemiplegia, aphasia, tonic
      clonic seizures and unconsciousness. The diagnosis was supported by CT, MRI and
      angio-MRI findings. The intensive i.v. heparin and streptokinase treatment, as
      well as antibiotics, resulted in full remission of all patient's symptoms. The
      case emphasizes the necessity of early diagnosis and management of cerebral
      venous sinus thrombosis.

PMID- 12523124
TI  - [Lateral medullary infraction due to left atrial myxoma--a case report].
AB  - A case of 53 year old women with Wallenberg syndrome due to atrial myxoma is
      reported. She was operated. Atrial myxoma on 7 x 8 cm was removed. After few
      months she can walk independently, she needs only a little help in everyday
      activities.

PMID- 12523126
TI  - [Polish-Italian Neurology Conference, Rimini, Sept. 29, 2001].

PMID- 12523125
TI  - [Blister-like aneurysm of anterior wall of the internal carotid artery, non
      related to arterial branches. Case report and review of literature].
AB  - The authors present (for the first time in polish medical literature) a case of a
      41-year old woman, presenting with subarachnoid haemorrhage due to ruptured
      blister-like aneurysm of the anterior wall of internal carotid artery, unrelated
      to any arterial branches. The patient was successfully treated surgically
      (clipping below the aneurysm base within the margin of normal parent artery
      wall). The authors present diagnostic and therapeutic difficulties of the case,
      which are characteristic of this type of aneurysms: 1. difficulty to diagnose the
      aneurysm in angiography (small size and blister-like shape) 2. high risk of
      massive bleeding and high surgical risk (danger of whole arterial wall rupture).
      3. specific surgical approach and technique: subpial dissection of the dome, use
      of clipgraft, or positioning the clip branches below the base of aneurysm within
      the margin of normal arterial wall (as the aneurysm dome is composed exclusively
      of adventitia and is not a part of artery wall. The authors discuss the
      peculiarities concerning the nature, localisation and possible mechanism of
      formation of this rare type of aneurysms. The analysis is based on the present
      case and on the review of literature.

PMID- 12523127
TI  - [Report on the 3rd World Congress in Neurological Rehabilitation, Venice, April 2
      6, 2002].

PMID- 12523137
TI  - [Heart transplantation--a 35th anniversary].

PMID- 12523138
TI  - [HIV in the neighbouring states].

PMID- 12523139
TI  - [The Dubrovka theatre rescue action].

PMID- 12523140
TI  - [A new therapeutic era for atopic eczema?].

PMID- 12523142
TI  - [Laparoscopic cholecystectomy].
AB  - Gallbladder stones are common, but most persons with stones are asymptomatic. The
      symptoms of gallbladder stones are usually characteristic. They are often
      associated with other types of abdominal symptoms, which are not affected by
      cholecystectomy. Day surgery laparoscopic cholecystectomy is increasingly
      popular. The operation may be associated with serious complications, but the risk
      is low. 85-90% of patients operated with cholecystectomy are asymptomatic after
      the operation.

PMID- 12523141
TI  - [Laparoscopic resection of the liver].
AB  - BACKGROUND: Liver resection performed by open surgery is standard treatment in
      selected patients with liver tumours. Recently, laparoscopic resection of the
      liver has been reported to be safe, with possible advantages to the patients such
      as reduced discomfort and shorter hospital stay. In this report we describe our
      preliminary experience with laparoscopic liver resection. MATERIAL AND METHODS:
      32 liver resections were performed in 19 patients during 23 procedures; i.e.,
      four patients had repeated resections. Indications were colorectal metastases (15
      patients), focal nodular hyperplasia (two patients), liver cyst (one patient) and
      metastasis from malignant melanoma (one patient). Three left lobectomies were
      done, the other resections were partial resections. RESULTS: Median duration of
      surgery was 187 minutes. Perioperative bleeding was median 650 ml. Tumour tissue
      was found in the resection margin in one patient and in three patients the
      resection margin was shorter than 1 mm. No procedures were converted to open
      resection. Median postoperative hospital stay was 3.5 days. Need of opioids were
      median 1 day. There was no 30 day mortality. INTERPRETATION: Laparoscopic liver
      resection is safe in selected patients, but randomized trials between open and
      laparoscopic resections are necessary.

PMID- 12523143
TI  - [Agenesis of the gallbladder].
AB  - BACKGROUND: Agenesis of the gallbladder, first described in 1701, is a rare,
      congenital malformation with an incidence of 0.01% to 0.04%. The condition can be
      associated with other and multiple anomalies. The diagnosis can be a random
      discovery during an abdominal operation or at autopsy, or an astonishing
      perioperative finding in a patient presenting with symptoms compatible with
      gallstone disease. MATERIAL AND METHODS: We present a young man with symptoms
      interpreted as related to gallstones. The preoperative ultrasound was
      misaprehended, describing a small, shrunken gallbladder filled with stones.
      RESULTS: At laparoscopy we found no gallbladder, but a small accumulation of
      connective tissue and a cord-like structure believed to be the cystic duct.
      Attempts to cannulate this structure failed. Postoperative endoscopic retrograde
      cholangiography (ERC) showed normal intra- and extrahepatic biliary ducts, but no
      gallbladder or cystic duct. Five years after the laparoscopy the patient still
      experiences attacks of pain located to the right hypogastric area.
      INTERPRETATION: Though agenesis of the gallbladder is a rare condition, surgeons
      and radiologists should be aware of it. Uncertain ultrasound pictures should be
      supplied by more advanced CT or MR techniques to avoid unnecessary operations
      searching for an absent gallbladder.

PMID- 12523144
TI  - [Treatment with statins: further data from the Heart Protection Study].
AB  - BACKGROUND: Statins have been shown to reduce cardiovascular disease in subjects
      with coronary heart disease, in men with high cholesterol levels and in men and
      postmenopausal women with low high-density lipoprotein cholesterol levels. In
      meta-analysis, reduction in events is associated with reduction in serum low
      density lipoprotein (LDL) cholesterol levels, however, some studies have proposed
      a threshold level for the effect. MATERIAL AND METHODS: A clinician and a
      statistician reviewed the Heart Protection Study in the context of previous
      similar studies. RESULTS: High-risk men and women (n = 20,536) aged 40-80 years
      with coronary heart disease, peripheral artery disease or diabetes and a
      cholesterol level of at least 3.5 mmol/l were randomised to simvastatin 40 mg or
      placebo. After 5.5 years, the incidence of nonfatal myocardial infarction or
      coronary death was reduced from 11.8% in the placebo group to 8.7% in the
      simvastatin group, and a similar reduction was seen in subjects with diabetes but
      no cardiovascular disease. There was no threshold of LDL cholesterol below which
      lowering it did not reduce risk. INTERPRETATION: The study adds to the body of
      evidence indicating that cholesterol lowering with statins is indicated for
      subjects with high risk and that LDL cholesterol reduction explains the reduction
      in events.

PMID- 12523145
TI  - [Individualized pharmacotherapy based on cytochrome P-450 (CYP) genotyping].
AB  - BACKGROUND: Genetic polymorphisms of the drug-metabolising cytochrome P-450 (CYP)
      enzymes CYP2C9, CYP2C19 and CYP2D6 have been characterized, and several of these
      variants lead to reduced or absent activity. This is of clinical importance
      mainly in patients having two non-functional alleles, phenotypically
      characterised as "poor metabolisers" (1-10% of Caucasians). Since most drugs are
      transformed into inactive or less active metabolites, "poor metabolisers" are at
      increased risk of developing drug induced adverse reactions. MATERIAL AND
      METHODS: Studies of relevant literature (MedLine search) in addition to our own
      experiences, show that CYP genotyping can predict the phenotype and thereby
      explain some abnormal drug responses and may be used to individualize
      pharmacotherapy. RESULTS: At present, CYP genotyping (CYP2C9/2C19/2D6) is most
      frequently requested in psychiatry and anticoagulant therapy, but the field is
      expanding. Important factors for implementation of pharmacogenetic methods are
      accuracy of diagnosis, quality of reports, response time, and cost.
      INTERPRETATION: Pharmacogenetic analyses will significantly contribute to
      reducing treatment costs for drug-induced adverse reactions and costs of sick
      leave, by predicting the best drug and the most effective and safest dosage. The
      expenses of full genotyping (CYP2C9/2C19/2D6) are equivalent to one day of sick
      leave. One might ask: Are pharmacogenetic analyses coming to the point where they
      drive down costs incurred by illness?

PMID- 12523146
TI  - [Cardiac natriuretic peptides as markers for cardiac disease--where do we stand
      today?].
AB  - BACKGROUND: A common denominator of many cardiac diseases is increased
      intracardiac pressure and wall stretch. This is accompanied by increased
      secretion from the heart of cardiac natriuretic peptides ANP and BNP and the N
      terminal part of their prohormones (Nt-proANP, Nt-pro-BNP). MATERIAL AND METHODS:
      Current evidence for the utility of cardiac natriuretic peptide measurements for
      diagnosis and follow-up of cardiac disease is reviewed. RESULTS: Published
      literature clearly indicates the usefulness of this kind of testing to the
      clinician diagnosing heart failure and estimating long-term prognosis. The value
      of repeated measurements for monitoring and tailoring of cardiac therapy is still
      under evaluation. INTERPRETATION: Cardiac natriuretic peptides are biochemical
      markers of cardiac function. Measurement of these peptides seems to be a
      significant diagnostic advancement. The precise role of this method in everyday
      clinical practice remains to be fully delineated.

PMID- 12523147
TI  - [Prioritization of hospital autopsies].
AB  - BACKGROUND: Routines for requesting autopsies in hospitals in Norway differ. At
      the Central Hospital in Rogaland, physicians usually fill out a form requesting
      an autopsy when a patient dies. The physician can choose between "high",
      "ordinary" or "low priority". In this study we investigated which patients were
      given highest priority and which factors influenced the priority made by the
      referring physician. MATERIAL AND METHODS: This was a retrospective study. All
      requests for an autopsy during the year 2000 were reviewed, except forensic
      medicine cases and perinatal deaths. We included 785 requests in the study. 237
      autopsies were performed: an autopsy rate of 30.2%. RESULTS AND INTERPRETATION:
      The requesting physicians considered 17% "high priority", 44% "ordinary priority"
      and 39% "low priority". Significantly higher priorities were set for those who
      died young, those who died after a short stay in hospital, and for those who died
      in intensive care units. Sex and time of death did not influence priorities. The
      recommendation required on the autopsy request form leads to more appropriate
      decisions by pathologists and strengthens the relationship between clinicians and
      pathologists.

PMID- 12523148
TI  - [Changes in drinking habits among Norwegian physicians 1985-2000].
AB  - BACKGROUND: The alcohol drinking habits in the Norwegian population has changed.
      We do not know whether this applies to doctors as well. In general, a possible
      association between job satisfaction and alcohol drinking habits has not been
      shown for doctors. MATERIAL AND METHODS: Cross-sectional questionnaire surveys of
      representative samples of Norwegian doctors in 1985, 1993 and 2000. RESULTS: 33%
      of the doctors drank alcohol more often than once weekly in 2000, versus 22% in
      1985. The pace of change accelerated between 1993 and 2000, compared to 1985 to
      1993. The proportion of doctors with a modified AUDIT score of 6 or more
      increased from 12% to 15% from 1993 to 2000, and the proportion with a modified
      AUDIT score of 13 or more increased from 0.6% to 1.3%. We found no correlation
      between job satisfaction and drinking habits. INTERPRETATION: The change in
      drinking habits among Norwegian doctors is similar to the change in the
      population at large. More frequent moderate consumption of alcohol has not been
      accompanied by less frequent consumption of larger amounts of alcohol.

PMID- 12523149
TI  - [Brachytherapy in prostatic cancer].
AB  - BACKGROUND: Brachytherapy is increasingly used in the treatment of early prostate
      cancer, but has not been implemented as a treatment option in Norway. Recent
      advances in imaging techniques and the radiation technology itself has
      facilitated improvements in and better standardisation of brachytherapy. MATERIAL
      AND METHODS: An group of expert assisted the Norwegian Centre for Health
      Technology Assessment (SMM) in a systematic review of the evidence on the
      clinical effectiveness of prostate brachytherapy. The literature was identified
      by a defined search strategy, and assessed for relevance and validity. Only
      controlled or comparative studies were included in the review. RESULTS: There
      were no randomized controlled trials or large prospective studies. Many of the
      relevant studies were of poor validity. None of the included studies had
      sufficient follow-up for overall or disease free survival. There were no
      differences between brachytherapy, external beam therapy or radical prostatectomy
      in disease free survival (PSA measures) or in rates of complications.
      INTERPRETATION: There is a lack of valid data from large prospective studies on
      the clinical effectiveness of brachytherapy. On the other hand, the clinical
      effectiveness of radical prostatectomy and external beam radiotherapy is also
      poorly documented. Results from one large randomized controlled trial comparing
      radical prostatectomy with brachytherapy in the USA will not be available within
      the next ten years.

PMID- 12523150
TI  - [Primary health care in Vestfold county prior and after the introduction of the
      primary health act].
AB  - A longitudinal analysis of the development of primary care in Norway focusing on
      Vestfold County shows that resources have increasingly been channelled to
      curative services, with less being spent on community-based preventive care.
      Vestfold, a county in the most densely populated area of Norway, with an
      expanding population and a growing economy, has seen a remarkable growth in
      private practice. There are several reasons for this. Socio-economic and
      demographic trends play a role; the provision of curative services is also more
      flexible and more profitable. Local municipalities seem to have given higher
      priority to curative services than to preventive tasks. Nation-wide, primary care
      has grown more slowly than specialised care. At the local level, care for the
      elderly, organised as a separate service, has been a winner.

PMID- 12523151
TI  - [Systemic antiviral treatment of genital herpes].

PMID- 12523152
TI  - [Darwinian logic--provocation and resource in medical thinking].

PMID- 12523153
TI  - [Physician-patient interaction and two concepts about communication].

PMID- 12523154
TI  - [Autopsies at Norwegian hospitals in 1984 and 2001].

PMID- 12523155
TI  - [Use and misuse of argumentation in the debate on stem cells].

PMID- 12523156
TI  - [Are muscular and articular pains more than functional diseases?].

PMID- 12523158
TI  - [Printing errors caused misunderstanding about euthanasia in the Netherlands].

PMID- 12523157
TI  - [Antioxidants again].

PMID- 12523159
TI  - [Our experiences in microvascular reconstruction with free forearm skin flap].
AB  - Free forearm skin-fascia flap was used at 14 patients for head and neck
      reconstruction. Tissue defect was located in mesopharynx at 6 patients, in
      piriformis recessus at 2, in buccal mucosa at 1, in hypopharynx 4 and very large
      defect embracing mesopharynx, hard and soft palate at one patient. To present
      moment lives 11 ill in this one from recurrent diseases. Most important element
      of microvascular junction is correctly executed venous junction. Patients after
      microvascular flaps showed less percentage of early complications (fistulas,
      shorter time of staging in Clinic). Connection of partial operation of the larynx
      with microvascular reconstruction of throat creates chance on good oncological on
      functional result. Free forearm skin-fascia flap provides good anatomical and
      functional result after various reconstructions of head and neck region.

PMID- 12523160
TI  - [Morphology and function of the pharyngoesophageal segment].
AB  - Basing on the review of the foreign and domestic literature the point of view
      concerning the anatomical structure, innervation and histomorphology of the
      pharyngoesophageal segment (pes) is being presented. Special attention was paid
      to the impact of the somatic and autonomic (particularly its sympathetic part)
      nervous system on the function of the pharynx, as well as the pressure at rest
      with the pharyngoesophageal sphincter. Histomorphologic investigations suggest
      that the pes function and tension of the particular pharyngeal constrictors
      (upper, middle and inferior) is determined by: a) structure, b) distribution of
      the IX and X nerve fibre ends in pharyngeal sphincters, c) structure of the
      pharyngeal sphincter, which is also supplied with the nervous fibre ends of the
      upper cervical sympathetic trunk. The sympathetic trunk is located on both sides
      of vertebral column from the skull base till the tip of the sacral bone. In case
      of degenerative process in the neck segment of the vertebral column, irritation
      of the sympathetic part of the autonomic system is taking place. Experimental
      investigations revealed that the stimulation of the sympathetic nervous fibres of
      the autonomic system results in weakening of the upper and middle pharyngeal
      sphincter's tension and increase of tension in its lower part (cricopharyngeal
      muscle). This can be an etiopathogenic factor under physiological condition in
      disturbances of the pharyngeal phase of deglutition act. After total
      laryngectomy, however, high pressure in the lower part of the pes (in the area of
      pharyngoesophageal sphincter) renders it difficult or even impossible to
      introduce the air into the esophagus to master the phonation and esophageal
      speech. The significance of the knowledge of the pes innervation in clinical
      practice is important for prognosis in mastering of supplementary, esophageal and
      shunt phonation.

PMID- 12523161
TI  - [Evaluation of mucosal acute radiation injury during accelerated-hyperfractionted
      split course radiotherapy (CHA-CHA) in advanced head and neck neoplasms].
AB  - The material consisted of 18 patients, a pilot group of randomised study
      regarding radiotherapy of advanced head and neck cancer with massive lymph nodes
      metastases using accelerated, hyperfractionated, split-course scheme (CHA-CHA).
      Patients were irradiated twice a day with 6 hours gap using fraction dose of 1.6
      Gy up to dose of 32 Gy. The same course of radiotherapy was repeated after 8 days
      of gap and treatment was completed within 28 days to avoid accelerated
      repopulation of tumour clonogens. The aim of the study was to assess the toxicity
      of treatment. The mucosal acute radiation injury using Dische scale and weight of
      patients were evaluated. The Severity-Time Units values were calculated and
      compared to conventional radiotherapy. The average "time-intensity" curves of a
      radiation reaction and an epitheliolisis were calculated. The reaction had
      dynamic growth up to 14 points within two weeks. Next two weeks of plateau was
      observed. The healing phase was three weeks long, but in some cases a value of 4
      points was still noted in the 20 week. The heaviest reaction appeared in the
      cases of oropharyngeal cancer. STU values differed significantly for CHA-CHA and
      conventional treatment. The big weight loss caused by malnutrition provoked by
      radiation reaction was found, but it never was a reason of the treatment gap. On
      the base of obtained results we form the conclusion that CHA-CHA scheme provokes
      dynamic and intensive radiation reaction which is well tolerated by patients and
      which is not a reason of consequential late effects.

PMID- 12523162
TI  - [Laser myringotomy].
AB  - The aim of the study was assessment of the qualities of laser-assisted
      myringotomy (LAM) as a treatment for acute and secretory otitis media. Laser
      assisted myringotomy was performed on 65 children (113 ears) mean age 6.2 years
      diagnosed with secretory otitis media (80%), recurrent secretory otitis media
      (11%) and acute otitis media (9%). Myringotomy was performed under general
      anesthesia using the OtoLAM device (ESC/Sharplan, Israel). In 64 ears pressure
      equalisation tubes were inserted after fenestration of the tympanic membrane with
      laser. Adenoidectomy alone or with tonsillectomy was performed at the same time
      in 51 cases. Laser tympanostomies remained patent for 7-32 days. All
      tympanostomies healed with no noticeable scarring. LAM appears to be a safe, and
      easy to performed, alternative technique in the treatment of otitis media.

PMID- 12523163
TI  - [Change in otosclerosis presentation over two decades].
AB  - Presentation of otosclerosis in eighties and nineties was compared on the basis
      of analysis of patients' documentation. A group I of 80 patients treated in 1980
      1990 and a group II of 148 patients treated in 1991-2000 were compared with
      regard to sex, age, incidence of oval window obliteration and bilateral disease.
      Bone conduction and air conduction threshold and air-bone gap were also compared.
      There was no difference between two groups regarding sex, age and bone conduction
      threshold. Oval window obliteration was found in 8 (10%) patients of group I and
      in 7 (4.7%) patients of group II and the difference was not significant.
      Bilateral otosclerosis was diagnosed in 77 (96.3%) patients of group I and in 121
      (81.8%) patients of group II and the difference was significant (p < 0.01). Air
      conduction threshold and air-bone gap in patients treated in nineties were
      significantly smaller than in eighties (p < 0.001). In the last decade patients
      with otosclerosis presented with smaller hearing loss, smaller air-bone gap and
      had bilateral disease less frequently than patients in eighties.

PMID- 12523164
TI  - [Value of free testosterone and estrogen-progesterone receptor concentration in
      juvenile patients with angiofibroma].
AB  - The same localisation, age and sex patients at juvenile nasopharyngeal
      angiofibroma may suggest relation its pathogenesis to hormonal changes of
      pubertal period. The examined group comprised 3 juvenile nasopharyngeal
      angiofibroma patients treated in ENT Clinic of K. Marcinkowski University of
      Medical Sciences in Poznan. There was estimated free testosterone (fT) level in
      blood serum. It was used radioimmunological assay Spectria by Orion Diagnostica.
      The concentration of estrogen and progesterone receptors was estimated by
      immunoenzymatic assay ER-EIA and PgR-EIA by Abbott. The quality assessment was
      done both in cytoplasmatic and nuclear receptors. There were normal value of free
      testosterone in blood serum at all patients. Samples of juvenile nasopharyngeal
      angiofibroma contain estrogen and progesterone receptors. We found much higher
      concentration of nuclear receptors comparing to cytoplasmatic ones.

PMID- 12523165
TI  - [Congenital cysts and fistulas of the neck].
AB  - On the base of literature and their own 123 patients the authors present the
      frequency, diagnostics and treatment of congenital neck fistulas and cysts. We
      had 9 congenital fistulas: 6 median and 3 lateral. We treated 114 patients with
      neck cysts.: 29 median and 85 lateral, from which 50 were at the right side. The
      disease mainly manifested in 10-19 year-old patients--25 cases and in 30-39 year
      old patients--21 cases. We divided the lateral neck cysts according to Bailey's-
      the most frequent of which were of III type--44.7%, II type--32.94%, IV type
      16.58% and I type 5.88%. All patients were radically operated on-that is they had
      totally enucleated fistula or cyst. In the case of median fistulas or cysts we
      didn't extirpate the body of the hyoid bone but in the case of duct going to
      caecal foramen of the tongue, we elevated the hyoid bone and with Storz lupe we
      prepared the duct to the root of the tongue. We didn't have any recurrence
      resulting from this kind of treatment. We had a recurrence in one patient (0.81%)
      with median cyst of the neck which was localised in the lower part of the neck
      and was connected with thyroid. We reoperated this patient and we had a complete
      recovery.

PMID- 12523166
TI  - [Potential use of cysteine endopeptidase inhibitors in radiodiagnostics of
      laryngeal and tongue neoplasms].
AB  - The methods applied up to now do not allow to define the border between the tumor
      and healthy tissue especially in advanced cases. Microlaryngoscopy facilitates
      the evaluation of the infiltration superficially, but does not allow for
      estimation its deeper penetration. CT and MRI often do not answer the question
      concerning the tumor spread as well. That is why the monoclonal antibodies marked
      with isotopes directed against specific antibodies of different neoplasms are
      applied in diagnostic. In the neoplasm development the great role play
      endopeptidases. They degrade the intercellular matrix and basement membrane and
      by this way made possible the neoplasm invasion. The high level of the
      endopeptidase in patients with neoplasm is a bad prognosis. The disposition of
      endopeptidase in neoplasm tissue is characteristic and gives opportunity to
      localise the border of healthy tissue thanks their inhibitors application. The
      inhibitor of cysteine endopeptidase obtained from hen egg and marked by J 125 was
      used in our study. The reaction between the cysteine endopeptidase inhibitor and
      malignant cells received directly from patients with tongue and laryngeal
      carcinoma and cells cultivated in vitro from the carcinoma.

PMID- 12523167
TI  - [Olfaction in congenital hypothyroidism].
AB  - The aim of the study is to present results of the olfactory testing in congenital
      hypothyroidism in the group of 20 subjects. The etiology of hypothyroidism
      included: Pendred's syndrome in 2 cases, hypoplasia in 2 cases, athyreosis in 5
      cases and ectopy of thyroid gland in 11 cases. Olfactory testing involved
      olfactometry by Elsberg-Levy modified by Pruszewicz for 4 odorants: coffee,
      lemon, mint and anise; smell fatigability test by Pruszewicz et al. for lemon.
      Level of plasma TSH was determined in each subject. Age of the subjects, at which
      hormonal replacement therapy was started and regularity of the treatment were
      taken into consideration. Obtained results: impaired odorant identification and
      shortened smell fatigability period prove a significant impact of thyroid status
      on central nervous system development most probably already prior to birth and on
      cognition processes.

PMID- 12523168
TI  - [The role of immunological factors in Meniere's disease].
AB  - Involvement of the immunological mechanisms in the pathogenesis of Meniere's
      disease has been discussed over the past two decades. Nevertheless, we lack well
      defined laboratory tests that might confirm the autoimmune background of the
      disorder. Therefore the diagnosis is often based solely on the patient's clinical
      profile and the positive response to the immunosuppressive therapy. In this
      article we present a case of 44 year-old woman with Meniere's disease
      successfully treated with systemic glucocorticoids. The pathogenesis, diagnosis
      and management of immune-mediated cases of Meniere's disease are reviewed.

PMID- 12523169
TI  - [Assessment of hearing organ ability in high-frequency auditory in patients
      suffering from chronic renal failure treated by haemodialysis and human
      recombinant erythropoietin (rhPEO)].
AB  - The problem of hearing loss occurrence in the course of chronic renal failure
      (CRF) was investigated in numerous research studies, attempting to explain both
      the etiological factors and treatment possibilities. According to various
      authors, the percentage of hearing loss occurrence in patients suffering from CRF
      differs between 20% and 80%. The idea of this paper is based on an observation
      that if peripheral blood parameters such; haemoglobin, amount of red blood cells
      improve when influenced by rhEPO, then tissue oxidation improvement connected
      with it causes also better metabolism of cilliar's cells, what helps to improve
      hearing. The purpose of this study has been to assess the influence of treatment
      with human recombinant erythropoietin obtained through genetic recombination and
      by haemodialysis upon the condition of the hearing organ in patients with CRF (as
      a result of both a single procedure and long-term treatment). 65 haemodialysed
      patients with chronic renal failure were enrolled in this study. 31 of them (with
      haematocrit value below 28%) were treated with rhEPO for 4 months (3 times a
      week, 4000 units). The remaining 34 patients (with haematocrit values of above
      28%) were not treated with rhEPO. Impairment of hearing was found in 87.1% of the
      CRF patients examined, while the hearing loss in high frequency range (9-18 kHz)
      was significantly more pronounced than those observed in the conventional range.
      In 70% of the patients the hearing loss was the cochlear type. Thus, combining
      haemodialysis with recombinant human erythropoietin in treatment of CRF patients
      results in significant improvement of hearing, correlated with positive results
      in fighting anaemia. The improved hearing found is, most surely, related to
      better oxygen supply of ciliated cells of internal ear, resulting from improved
      oxygen supply in peripheral blood and tissues of the body, and may also be
      related to the centric activity of erythropoietin, as the presence of receptors
      for EPO was found in the central nervous system (CNS) neurocytes, and it was also
      proven that EPO is produced in CNS, probably in astrocytes.

PMID- 12523170
TI  - [The influence of haemodialysis on hearing organ of children with chronic renal
      failure].
AB  - Haemodialysis applied in terminal phase of chronic renal failure causes
      considerable metabolic and electrolyte disturbances within a few hours in human
      organism. The aim of the work was an evaluation of the influence of those
      disturbances on hearing organ as potential factors being responsible for
      perceptive hearing loss in considerable number of the patients with chronic renal
      failure (CRF). Examination was conducted on 20 children with CRF, aged 10-18
      years. In each case, before and after dialysis, on the same day, ENT examination,
      pure tone audiometry, brain auditory evoked potentials (BAEP) and acoustic
      otoemissions (TEOAE, DPOAE) were performed. Audiometric tests revealed
      significantly worse hearing in children with CRF in comparison to healthy
      subjects with not statistically significant improvement after dialysis.
      Significantly elongated I, III, V peak latencies as well as I-III and I-V
      interpeak latencies in BAEP of children with CRF before dialysis were
      considerable shorter after dialysis except III-V but in 2 of them they appeared
      after dialysis. In 8 CRF cases DPOAE was present after dialysis in the range of
      frequencies absent before and in 9 CRF cases there was an increase of the
      response on the level of 10-15 dB for some frequencies. There were no any changes
      after dialysis in 3 cases with CRF. The results of our studies reflect
      subclinical disturbances in neural conduction of auditory pathway and its
      significant improvement after normalisation of blood parameters (uremic toxins,
      hyperkalaemia). This fact suggests central component of ureic axonopathy in the
      pathogenesis of hearing impairment in children with CRF. Dynamism of the changes
      in TEOAE and DPOAE reflects also the influence of those disturbances on auditory
      cells on the level of the labyrinth.

PMID- 12523171
TI  - [Objective audiometry in diagnosis of tinnitus].
AB  - During last 3 years there have been 900 tinnitus patients treated at ENT
      Rehabilitation Center in Poznan. Everyone underwent a thorough laryngological and
      audiological examination. Diagnostic procedure comprised also neurological and
      endocrinological consultations with accessory blood tests. Wide group of
      audiological tests used for diagnosis was divided into objective (BERA, OAE,
      tympanometry, stapedius reflex) and subjective (pure tone audiometry, speech
      audiometry, suprathreshold audiometry) methods. Otological diagnostic in tinnitus
      patients is difficult due to its subjective character. That is why it is so
      important to have objective methods for its evaluation. In this paper authors
      present results of BERA tests and impedance conducted on group of 900 patients.
      Performed objective tests enabled to diagnose otosclerosis, chronic otitis media
      and pathology in cerebello-pontine angle in patients without any abnormalities on
      physical examination.

PMID- 12523172
TI  - [Hearing loss in patients with diabetes mellitus type II].
AB  - Hearing threshold of 40 patients with diabetes mellitus type 2 and 20 healthy
      controls were determined using pure tone audiometry of frequencies 500, 1000,
      2000, 4000, 6000 and 8000 Hz and evoked otoacoustic emissions (EOAEs). The
      hypoacusis was bilateral, progressive and neurosensory nature, affecting the
      higher frequencies. Subjects with diabetes type 2 were more likely to have a
      hearing loss than were subjects without diabetes (95% vs 65%). This difference
      was statistically significant. Hearing loss was significantly correlated with age
      and duration of diabetes. Evoked otoacoustic emissions found out only in 2
      patients with normal hearing. The results suggest that EOAEs doesn't show
      subclinical cochlear damage in diabetic patients because of the significant
      hearing loss.

PMID- 12523173
TI  - [The examinations of hearing in infants treated in neonatal intensive care
      units].
AB  - The aim of the study was the estimation of hearing and the analysis of the risk
      factors for hearing loss in infants treated in neonatal intensive care units. The
      examinations were performed in 287 infants, who we examined in ENT Department
      between the ages of three and six months after discharge from neonatal intensive
      care unit. The infants were investigated with the use of ABR elicited with clicks
      and tone burst of 500 and 1000 Hz. Elevated auditory thresholds were found in 48
      neonates in the first examination and in 27 in the second examination. Among the
      risk factors we observed the most frequently: gestational age < 33 Hbd, birth
      weight < 1500 g, respiratory and cardiovascular disorders and intracranial
      haemorrhages.

PMID- 12523174
TI  - [Rare case of a large foreign body in the orbital region].
AB  - The authors described a case of the patient with a foreign body of the orbit,
      which was glass-baquette. Arrived she at orbit by chance by skin of bottom eyelid
      below medial of angle of eye. Glassy foreign body (lengths about 6 cm) was
      removed during operation. We did not observe postoperative complications, over
      injury of lacrimal ducts.

PMID- 12523175
TI  - [Mucoepidermoid carcinoma of the larynx].
AB  - Mucoepidermoid carcinoma is classified among the salivary gland tumors and is
      commonly found in the parotid gland. In the larynx it is an uncommon tumor that
      occurs mostly in men. There have been only about 100 cases of laryngeal
      mucoepidermoid carcinoma reported in the literature. Three cases of
      mucoepidermoid carcinoma of the larynx are reported. First case--tumor T1N0
      localised on the vocal cord was removed using Kleinsasser method. Second and
      third case--tumor T3N0 was removed by total laryngectomy. The inherent
      difficulties in histologic diagnosis are noted and treatment of mucoepidermoid
      carcinoma is discussed. The available literature is reviewed.

PMID- 12523176
TI  - [The case of haemangiofibroma after prolonged intubation in 12-years old child].
AB  - Authors presented a case of haemangiofibroma of larynx after prolonged intubation
      in 12 years old girl. We pay attention mechanism of larynx injury after prolonged
      intubation. In our opinion endoscopy is a very valuable method of child larynx
      examination.

PMID- 12523177
TI  - [Middle ear tuberculosis behind an intact tympanic membrane--a case report].
AB  - An extremely rare case of the 21 years women with the tuberculosis of the
      tympanic cavity behind the intact tympanic membrane was presented. The authors
      have described the clinical picture, diagnosis difficulties and ways of therapy.
      A surgical treatment and antituberculosis treatment was satisfactory.

PMID- 12523178
TI  - [Transgenic plants].
AB  - Advances in molecular genetics and recombinant DNA technology have revolutionized
      our understanding of the pathogenesis as well as the diagnosis, therapy and
      prevention of human diseases. Similar developments characterize plant
      biotechnology with the production of plant derived biomedical as well as health
      products. Apart from the fundamentals of molecular plant genetics, the production
      of transgenic plants as well as the clinical relevance, benefits, limitations and
      potential problems of plant biotechnology will be reviewed in some detail. It is
      a particular challenge to physicians in an increasingly informed environment to
      be informed about the new developments in molecular biology and recombinant DNA
      technology and to have a qualified opinion about their clinical relevance.

PMID- 12523179
TI  - [Embryonic and adult stem cells].
AB  - Stem cells possess an unlimited potential to regenerate and can acquire the
      identity of various differentiated cells. In the case of embryonic stem cells all
      the different cells of an organism can be generated. Recently the hitherto
      underestimated differentiation potential of adult stem cells has also taken
      center stage. These findings have opened up new perspectives in transplantation
      medicine and cell therapy for degenerative diseases. Before these possibilities
      can be realized, however, a number of ethical and scientific-technical obstacles
      have to be overcome. The latter are caused for example by the low abundance of
      the cell material as well as by possible immunological rejection reactions.

PMID- 12523181
TI  - [Molecular diagnostic tools in gastroenterology].
AB  - Molecular biology has become an integral part of modern medicine. Novel molecular
      methods have yielded great progress in early detection, classification and
      management of a variety of diseases. This review discusses principles and
      applications of molecular diagnostic tools in the field of gastroenterology.

PMID- 12523180
TI  - [Inherited and acquired disorders of mitochondrial DNA].
AB  - Human mitochondrial DNA (mtDNA) resides in thousands of copies in each cell and
      encodes for 13 structural proteins which are subunits of the respiratory chain.
      Point mutations, deletions, and decreased copy-number (mtDNA-depletion) are now
      functionally and genetically linked to human disease. Although mtDNA is inherited
      maternally, some mutations may arise spontaneously and others are inherited in a
      mendelian fashion, which is attributed to defective nuclear genes. MtDNA
      mutations are also associated with aging and with tumors but in these conditions
      probably not of functional significance. Mutations of mtDNA may be acquired by
      exposure to toxic substances (such as alcohol or doxorubicin). An acquired copy
      number defect (mtDNA-depletion) is dose-limiting for some antiviral nucleosides
      and nucleotide analogues. The internist encounters predominantly myopathies,
      cardiomyopathies, lactic acidosis or diabetes mellitus but mtDNA-changes also
      lead to neurological, hematological and renal symptoms. A syndrome of fat
      redistribution, termed lipodystrophy, is now observed with long-term therapy of
      HIV-patients and has been associated with mtDNA-depletion. Therapy with vitamins,
      radical scavengers and L-carnitine is recommended, but of limited success.

PMID- 12523182
TI  - [Bed needs and speech acrobatics].

PMID- 12523183
TI  - [Drug reimbursement--an international headache].

PMID- 12523184
TI  - [What place does ultrasonography have in inflammatory bowel disease?].

PMID- 12523185
TI  - [Ultrasonography in inflammatory bowel diseases--preliminary results].
AB  - BACKGROUND: After installing an ultrasound machine within the gastroenterologic
      unit at Alesund Hospital in February 2001, we wanted to evaluate its usefulness
      in inflammatory bowel diseases compared with endoscopy. MATERIAL AND METHODS: We
      describe findings in 22 patients investigated from February to December 2001.
      Ultrasonography was performed using a combination of B-mode, power Doppler and
      duplex Doppler ultrasound techniques. The bowel disease was diagnosed by
      histology in all patients. RESULTS: Ultrasonography revealed wall thickness,
      disease extent and hyperaemia within the pathological segment of the bowel in all
      patients. Furthermore, the method demonstrated several pathological conditions
      related to the bowel disease which were not revealed by colonoscopy.
      INTERPRETATION: Transcutaneous abdominal ultrasonography gives additional
      information to endoscopy in patients with inflammatory bowel diseases.

PMID- 12523186
TI  - [Laparoscopic fundoplication for gastroesophageal reflux disease].
AB  - BACKGROUND: In 1995 we introduced laparoscopic technique as routine for
      fundoplication for gastro-esophageal reflux disease. MATERIAL AND METHODS: 222
      patients were scheduled for laparoscopic fundoplication; the operation was
      completed laparoscopically in 219 patients. They all had an observation period of
      one year as a minimum; 205 patients returned a follow-up questionnaire. RESULTS:
      12 patients had major complications, six of them have been reoperated. At follow
      up, 95% reported excellent or good results, 3% had persisting reflux symptoms, 4%
      had moderate to severe dysphagia and 17% had moderate to severe gas bloat
      syndrome and flatulence problems which adversely affected an otherwise good
      outcome. Thus, 63% reported excellent, 23% good and 7% fair outcome, and 6% were
      moderately or very dissatisfied. Bloating and increased flatulence were the major
      reasons for dissatisfaction. INTERPRETATION: The risk of troublesome
      postoperative bloating and flatulence should be addressed thoroughly during the
      preoperative information, and especially in patients who have similar symptoms
      preoperatively.

PMID- 12523187
TI  - [Calicivirus and acute gastroenteritis].
AB  - BACKGROUND: Outbreaks of calicivirus gastroenteritis are common during the winter
      season, especially among elderly residents in institutions. The outbreaks are
      often difficult to control in institutions and may occasionally result in closure
      of wards. Reliable diagnostic methods are therefore important. We have studied
      the prevalence of calicivirus in samples sent to our laboratory for calicivirus
      detection during the winter season 2001 to 2002. MATERIAL AND METHODS: The
      presence of calicivirus was studied by nested RT-PCR. A total of 117 faecal
      samples obtained from patients with suspected calicivirus gastroenteritis were
      examined. RESULTS: Sixteen outbreaks of acute gastroenteritis were observed
      during the study period. While calicivirus was confirmed in nine of the
      outbreaks, the virus was detected in only 25 of the 117 faecal samples analyzed
      (21%). An increased detection rate was observed when faecal samples were
      collected during the first two days after onset of symptoms. INTERPRETATION:
      Appropriate surveillance systems are required in order to control calicivirus
      gastroenteritis in institutions. Microbiological laboratories should be aware of
      the importance of collecting specimens during the acute phase (i.e., within 48-72
      hours after onset) of illness.

PMID- 12523188
TI  - [Headache with transient neurologic deficits and lymphocytosis in the
      cerebrospinal fluid].
AB  - BACKGROUND: Patients with episodes of headache associated with transient
      neurologic deficits and lymphocytes in the cerebrospinal fluid have been reported
      over the last two decades. MATERIAL AND METHODS: We present five patients without
      a prior history of migraine who experienced a limited series of 1-10 episodes of
      headache associated with transient neurologic deficits and lymphocytosis ranging
      from 85 to 500 x 10(6)/l in the cerebrospinal fluid. RESULTS: Some patients had
      elevated protein levels in the cerebrospinal fluid and focal EEG pathology.
      Analysis of cerebrospinal fluid, blood tests and imagining investigations did not
      give plausible aetiological explanations. INTERPRETATION: The prognosis of this
      syndrome is good. Its aetiology is unknown. It is reasonable to search for
      neurotropic viruses in future cases.

PMID- 12523189
TI  - [Smoking cessation intervention and barriers against it among general
      practitioners in Vest-Agder county].
AB  - BACKGROUND: The aim of this study was to evaluate enquiry about smoking and to
      identify the barriers to engaging in tobacco prevention among general
      practitioners (n = 147) in Vest-Agder county, Norway in 2001. MATERIAL AND
      METHODS: The questionnaire was basically the same as used in a national survey in
      1999. RESULTS: If the patient did not have smoking related symptoms, GPs enquired
      about smoking in only 30% (mean) of cases. If the patient had such symptoms, the
      enquiry rate was 95%. If GPs were aware of their patients' smoking habits, they
      informed about the advantages of quitting smoking in approximately 2/3 (mean) of
      cases. Few engaged in smoking cessation support. The main experienced barrier to
      engage in smoking cessation was that it was time consuming. Half of the GPs would
      have preferred to refer those who wanted to quit to experts in smoking cessation.
      Approximately two thirds answered that they enquired more frequently about
      smoking habits in 2001 than in 1999, but survey data from 1999 suggests that
      enquiry rates remained unchanged from 1999 to 2001. INTERPRETATION: GPs enquired
      possibly more frequently about smoking habits in 2001 than in 1999. The main
      barriers to engaging in tobacco prevention were considered smaller the more the
      GPs approached practical smoking cessation work.

PMID- 12523190
TI  - [Bupropion as an aid for smoking cessation].
AB  - BACKGROUND: Quitting smoking is a primary lifestyle option for reducing the risk
      of a number of diseases. Effective therapies include counselling, nicotine
      replacement and bupropion, a dopamine and noradrenaline reuptake inhibitor.
      MATERIAL AND METHODS: Double-blind, placebo-controlled studies with > or = 100
      subjects identified through the Cochrane database or presented by the author at a
      congress are reviewed. RESULTS: Bupropion initially increased quit rates in a
      dose-dependent manner among healthy smokers treated at specialist clinics. Recent
      trials have included smokers treated in a wider range of settings and in
      subgroups who often experience difficulties in quitting, including smokers with
      pulmonary or cardiovascular disease and smokers who relapsed after previous
      treatment with bupropion. In three studies reporting twelve-month results, quit
      rates were 27-30% for bupropion compared to 12-16% for placebo and continuous
      abstinence rates were 18-22% compared to 6-11% for placebo. In meta-analysis the
      odds ratio for smoking cessation of bupropion versus placebo was 2.16 (95%
      confidence interval 1.51-3.10) with combined data for six and twelve months of
      continuous abstinence. Bupropion was well tolerated in all the trials and is
      recommended in US and UK guidelines. INTERPRETATION: Physicians should recommend
      medication for smoking cessation for patients with no contraindications because
      of the enormous benefits of quitting.

PMID- 12523191
TI  - [Telephone Quitline and changed smoking behavior].
AB  - BACKGROUND: The purpose of this study was to find out whether and to what exTent
      callers to the Norwegian Quitline changed their smoking behaviour, and whether
      change was influenced by the degree of Quitline follow-up. MATERIAL AND METHODS:
      Two groups were studied and compared after their own initial call. The follow-up
      group (n = 324) received information material and four consultations. The
      registration group (n = 272) received material and two consultations. RESULTS:
      Both groups showed significant improvement over a year. In the follow-up group
      18% and in the registration group 13% of individuals had changed from daily
      smokers to non-smokers. The behavioural change was significantly better in the
      follow-up group. INTERPRETATION: The results indicate that individuals seem to
      benefit from consultation. More frequent and systematic contact with a
      professional appears to have a positive effect on the quitting rate.

PMID- 12523192
TI  - [Evaluation of reimbursement applications for new drugs].
AB  - BACKGROUND: It has been suggested that decisions about which drugs should be
      reimbursed by the Norwegian National Insurance Administration (NIA) are ad hoc
      and made without explicit criteria for evaluating applications. MATERIAL AND
      METHODS: We assessed all documents that we were able to retrieve from the NIA for
      a sample of 31 applications to add new drugs to the drug benefit program, mainly
      in the 1990s. The assessment was done with respect to two questions. First, to
      what extent were different factors explicitly evaluated, such as treatment
      effects, side effects, cost-effectiveness and reimbursement costs? Second, to
      what extent did these factors affect the decisions that were made? RESULTS: We
      found documents for 19 of the 31 drugs. For the 19 drugs and nine factors that we
      considered as potentially important in making a decision (a total of 19 x 9 = 171
      possible assessments), we found a total of only eight explicit written
      evaluations. In 10 out of 19 cases costs to the NIA and control of these costs,
      or use of the drug, appeared to have an important impact on the decision that was
      reached. INTERPRETATION: Based on the documents to which we have had access, the
      NIA's evaluations have not been systematic or transparent for the vast majority
      of drugs.

PMID- 12523193
TI  - [Colorectal cancer and ulcerative colitis--which patients should be checked?].
AB  - BACKGROUND: Colonoscopy screening has been recommended as the method for
      preventing the development of cancer in ulcerative colitis. Factors that increase
      the risk of developing cancer are early onset of the disease, widespread disease,
      and a duration of over 10 years. MATERIAL AND METHODS: The results of screening
      have been disappointing. A critical review of relevant publications is given.
      RESULTS: Recent data have shown that the cancer risk in ulcerative colitis is
      lower than previously thought. One of the most important reasons seems to be the
      treatment with salazopyrine and 5-aminosalicylic acid. INTERPRETATION: Systematic
      follow-up of these patients by means of colonoscopy should include those who do
      not tolerate long-term medical treatment, patients with early onset of total
      colitis and protracted disease, and finally patients with higher risk of
      colorectal cancer because of their family history.

PMID- 12523194
TI  - [Drug approval in Norway].

PMID- 12523195
TI  - [Controlled clinical trials--the pursuit ot true therapeutic effect].

PMID- 12523196
TI  - [Analytical epidemiology--case-control and cohort studies].
AB  - BACKGROUND: "The study of the occurrence of disease" is a short but quite precise
      definition of epidemiology, as it includes both descriptive and analytic
      approaches. Whereas descriptive studies of the distribution of diseases and their
      potential causal factors may generate hypotheses about disease aetiology, causal
      inferences may most safely be drawn from analytical testing through properly
      designed observational studies. METHODS: The most commonly used observational
      designs are the retrospective case-control and the prospective cohort studies. In
      some respects the two designs complement each other. Drawing on some classic
      epidemiological studies, their main properties in terms of what questions they
      may answer, what their applicabilities are, as well as their main strengths and
      weaknesses, are discussed.

PMID- 12523197
TI  - [Screening of 40-year-olds--400,000 men and women attended].
AB  - Over the period 1984-99, 400,000 Norwegian men and women aged 40-42 attended
      cardiovascular screenings carried out by the national health screening service.
      The data are available for research on application to the Norwegian Institute of
      Public Health. Details on the data and applications procedures are given in this
      article.

PMID- 12523198
TI  - [Can we rely on drug information?].

PMID- 12523199
TI  - [The concept "functional disorders" gives evidence about the dysfunctional
      theoretical basis of biomedicine].

PMID- 12523200
TI  - [Mirror, mirror on the wall, who is the fairest of them all?].

PMID- 12523201
TI  - [COX-2 inhibitors to patients with inflammatory bowel disease].

PMID- 12523202
TI  - [Use of specialist health care by the population].

PMID- 12523203
TI  - [Can specialist health care be used in a better way?].

PMID- 12523204
TI  - [Unethical article on anticholesteremic agents].

PMID- 12523205
TI  - [Nosocomial infections in nursing homes in Oslo].

PMID- 12523206
TI  - [Reorientation therapy--ethically inexcusable?].

PMID- 12523207
TI  - [Value of health care research only as hot news?].

PMID- 12523208
TI  - [Why do we vaccinate children against infections?].

PMID- 12523209
TI  - [MMR vaccination and autism--a population-based follow-up study].
AB  - INTRODUCTION: It has been suggested that the measles-mumps-rubella (MMR)
      vaccination causes autism. MATERIAL AND METHODS: We conducted a retrospective
      cohort study of all children born in Denmark from January 1991 through December
      1998. The cohort was established based on data from the Danish Civil Registration
      System. A unique person identifiable number given to all subjects enabled linkage
      with other national registries. MMR vaccination status was obtained from the
      Danish National Board of Health. Information on the children's autism status was
      obtained from the Danish Psychiatric Central Register which contains information
      on all diagnoses received from psychiatric hospitals, psychiatric wards, and
      outpatient clinics in Denmark. We obtained information on potential confounders
      from the Danish Medical Birth Registry, the National Hospital Registry, and
      Statistics Denmark. RESULTS: In the cohort of 537,303 children (2,129,864 person
      years), 440,655 children had been MMR vaccinated. We identified 316 children with
      a diagnosis of autistic disorder and 442 with a diagnosis of other spectrum
      disorders. After adjusting for potential confounders, the risk for autistic
      disorder and other spectrum disorders was not increased in vaccinated compared
      with unvaccinated children (relative risk 0.92; 95 percent confidence interval,
      0.68 to 1.24 and relative risk 0.83; 95 percent confidence interval, 0.65 to
      1.07). There was no association between age at vaccination, time since
      vaccination or calendar period at time of vaccination and development of autistic
      disorder. DISCUSSION: This study provides strong evidence against the hypothesis
      that MMR vaccination causes autism.

PMID- 12523210
TI  - [Risk of measles epidemic in Denmark].

PMID- 12523211
TI  - [The knowledge about measles, mumps and rubella among parents in the county of
      Roskilde].
AB  - INTRODUCTION: The aim was to determine how much knowledge parents have of MMR
      diseases and the side effects of the vaccine, and what influence this has on
      acceptance of the vaccination programme. MATERIALS AND METHODS: Sampling three
      districts of Roskilde County was done by the distribution of 1867 questionnaires
      to the parents of children aged 0-15 years in 22 institutions and schools (1
      January to 28 February 2000). RESULTS: Of the 878 (47%) replies, 825 (94%) had
      followed the vaccination programme. There was no difference between those who had
      followed the programme and those who had not with respect to reports of
      complications to the diseases, but the latter group reported more complications
      to the vaccine. In the vaccinated group, there were significantly more who stated
      that the doctor's opinion of the vaccine was positive, and acceptance of the
      remaining vaccination programme was also greater in this group. More children in
      the non-vaccinated group were involved in the decision about vaccination.
      DISCUSSION: Though knowledge of the diseases does not seem to influence the
      decision about vaccination, the responses raise the question of how information
      is to reach the general public. An open debate is needed on vaccination
      complications, as it is these or uncertainty about them that seem to influence
      the parents' choice. For 70% of parents, the doctor is their source of
      information, and it is therefore important for acceptance of the MMR vaccine that
      doctors have a positive view and are able to communicate this view to the
      parents.

PMID- 12523212
TI  - [An outbreak of measles in the county of Northern Jutland].
AB  - INTRODUCTION: With the introduction of MMR vaccination in the childhood
      vaccination programme in 1987, measles in Denmark is now rare. However, sub
      optimal vaccination coverage results in the accumulation of susceptibles and
      outbreaks may still occur. MATERIAL AND METHODS: Information from epidemiological
      investigations and experience gained from the management of measles cases in a
      children's ward in Aalborg Hospital are described. RESULTS: A nine-year-old child
      was admitted with a tentative diagnosis of travel associated clinical malaria.
      The patient was not isolated and information on possible exposure to measles was
      only obtained upon discharge. Laboratory confirmation was received ten days after
      admission. At this time, a previous close-contact patient was re-admitted with
      high grade fever. This second patient was isolated following laboratory
      confirmation, and other hospitalised children received passive immunization. A
      total of 24 cases were reported, of which 12 patients were infected whilst
      hospitalisation and 21 were unvaccinated against measles. DISCUSSION: In a sub
      optimally immunized population the introduction of measles virus may cause an
      outbreak in a local setting including a hospital environment, with potential
      spread to other geographical areas and hospitals. Obtaining a history of possible
      exposure to childhood infections, irrespective of the vaccination status, becomes
      highly significant upon admission. In the case of measles a detailed travel
      history is essential.

PMID- 12523213
TI  - [Nutrition and aging].

PMID- 12523214
TI  - [The impact of selected environmental factors on the morbidity of children in day
      care centers].
AB  - The purpose of this review was to present the existing evidence of the relation
      between children's absence from day-care centres caused by disease and
      environmental factors, such as hygienic standard, space per child, and indoor
      climate in day-care centres. The review is based on results from cohort studies
      and randomised, controlled studies identified through literature searches. There
      is good evidence that improved hand hygiene may reduce the morbidity and absence
      among children attending day-care centres. The effect of the efforts varies from
      a few to 50 per cent. On the background of cohort studies there is some evidence
      that available space per child in the day-care centres is also correlated to the
      rate of absence caused by diseases. The impact of noise and indoor climate in day
      care centres and the time spent outdoors has so far only been sparsely
      investigated but seems to be of some importance.

PMID- 12523215
TI  - [Health status of asylum seeking children].
AB  - INTRODUCTION: The aim of this investigation was to describe asylum seeking
      children's social and family situation, health status, strain factors connected
      with migration, and to unveil practice relevant indicators, which can furthermore
      delimit children with special needs. MATERIAL AND METHODS: A cross section
      investigation of asylum seeking children, who in the first half of 1997 were
      accommodated in The Danish Red Cross Reception Centre and examined by a doctor
      and/or a public health nurse according to the rules laid down by The Danish Red
      Cross Social and Health Department. If language problems occurred, an interpreter
      was present at the examination. Data were collected from the medical record of
      the child and the parents. RESULTS: The investigation included 364 children. 59%
      of the children had 306 diagnoses or symptoms, 17% of the diagnoses or symptoms
      were referred to a specialist or a psychologist. The children came from 25
      different countries. 43% came with both parents. The most frequent symptoms in
      the children were tooth and skin problems and enuresis. DISCUSSION: On the
      background of disease prevalence, asylum seeking children do not seem to be more
      frequently ill than children living in Denmark. It is considered that the present
      investigation could successfully be repeated with a view to universal validity.
      In the medical records, asylum seeking children's physical health situation is
      well described, whereas symptoms arising from the flight and experiences are
      sparsely described. It is recommended that an investigation is carried out, in
      which both the children's physical and mental health situation is described.

PMID- 12523216
TI  - [Lactic bacteria and other probiotics in infections and inflammatory diseases in
      children. What do we believe? - What do we know?].
AB  - Probiotics are microorganisms which, when ingested, may have a positive effect in
      the prevention or treatment of a specific pathologic condition. Probiotics are
      used for a number of gastrointestinal and certain systemic infectious and
      inflammatory diseases. The efficacy of selected probiotics to promote recovery
      from acute viral gastroenteritis in young children is well-documented. However,
      the role of probiotics in systemic diseases, e.g. atopic dermatitis, need to be
      confirmed in larger randomised controlled trials. This paper describes the
      theoretical background for the use of probiotics and reviews results from
      randomised controlled trials describing the effect of probiotics, particularly in
      paediatric diseases.

PMID- 12523217
TI  - [Body mass index. Reference values for 0-45-year-old Danes].
AB  - INTRODUCTION: Our aim was to establish body mass index (weight/height2 [kg/m2],
      BMI) reference values for 0- to 45-year-old Danes. MATERIAL AND METHODS: A
      national sample that was used to generate the current Danish height and weight
      reference (29,106 measurements in 1965-1977; age 0-21 years; sample I). Four
      samples from Copenhagen (3391 measurements in 1981-1985; age 7-45 years; samples
      II and III and 2608 measurements in 1991-1994; age 6-45 years; samples IV and V).
      With the LMS method for smoothing the curves, Danish BMI reference values by age
      and sex were constructed from samples I and II. BMI values from two recently
      examined, but smaller, Danish cohorts (samples IV and V) were compared with the
      reference values to assess the secular trend in BMI. RESULTS: The Danish BMI
      reference values are presented graphically. Graphs can be downloaded from
      http://www.paediatri.dk. In the more recently examined samples, the mean BMI was
      significantly increased in children and adolescents (SD score 0.19, P = 0.0007),
      but unchanged in young adults (SD score 0.01, P = 0.49). DISCUSSION: For clinical
      purposes, we recommend comparison of the BMI of Danish children and adolescents
      with the present Danish reference values and new internationally based cut-off
      values. The BMI of Danish adults should be compared with the WHO cut-off values.
      Cut-off values or national or internationally used BMI reference values can be
      used for research, depending on the purpose.

PMID- 12523218
TI  - [Smoking patterns among boys and girls in Danish elementary school classes].
AB  - INTRODUCTION: The objective was to study the correlation between male and female
      smoking prevalence in elementary school classes at grade nine through group-level
      analysis. MATERIAL AND METHODS: Data was collected by the 1998 Danish
      contribution to the cross-national study Health Behaviour in School-Aged
      Children. A standardised questionnaire was applied. This study included ninety
      school classes at grade nine (1515 students) from a random sample of schools in
      Denmark. The outcome measure was the proportion of male and female smokers in the
      school classes. RESULTS: The proportion of male and female smokers within the
      school classes did not correlate. For both boys and girls there was a high
      variation in the proportion of smokers between the school classes. DISCUSSION:
      The smoking-related social processes that exist in the school classes probably
      operate in a sex-differentiated manner. The effect of the classroom environment
      on the students' smoking behaviour must be considered differently for boys and
      girls.

PMID- 12523219
TI  - [Impact of a 10-year nation-wide campaign on knowledge of sensible drinking
      limits in Denmark].
AB  - INTRODUCTION: In Great Britain and in Denmark, strong efforts have been made to
      influence knowledge on the upper threshold of hazardous drinking. In Denmark, a
      campaign has been repeated every week 40 from 1990 to 2001 with information on
      the sensible drinking limits of 21 drinks per week for men and 14 drinks per week
      for women. The aim of this study was to examine the effect of this ongoing
      campaign on the level of knowledge of sensible drinking limits for men and women.
      MATERIAL AND METHODS: Every year from 1994 to 1999, random representative samples
      of 1,030 adult Danes were interviewed on the telephone. RESULTS: Our main finding
      was that the level of knowledge of sensible drinking limits for own sex increased
      in all subsets of the population throughout the period. However, at the end of
      the study period (1999), a total of 80% of highly educated young (18-25 years of
      age) men knew sensible drinking limits for own sex, while only 35% of uneducated
      older (more than 65 years old) men had knowledge on sensible drinking limits. The
      proportions were similar among women: Subjects admitting an intake higher than
      sensible for own sex, i.e. 21 and 14 drinks per week, respectively, had the
      highest knowledge of these drinking limits. DISCUSSION: We conclude that public
      health campaigns, such as the sensible drinking limit campaign, certainly has an
      impact on the level of awareness in the general population. Furthermore, those
      drinking more than 21 and 14 drinks per week, respectively, are reached by these
      campaigns.

PMID- 12523220
TI  - [Suicide among young people--familial, psychiatric and socioeconomic risk
      factors. A nested case-control study].
AB  - INTRODUCTION: The objective of the study was to estimate the risk of adolescent
      and early adulthood suicide related to adverse family and individual backgrounds.
      MATERIAL AND METHODS: The 496 young people aged 10-21 years who committed suicide
      during the period 1981-1997 in Denmark and 24,800 gender-age-time-matched
      controls. RESULTS: Parental suicide, early death, hospitalised mental illness,
      unemployment, low income, educational underachievement, parental divorce, mental
      illness in siblings, as well as mental illness and shorter schooling in the
      adolescents themselves were associated with increased risk of suicide. In the
      multivariate analysis, the odds ratios associated with suicide or mental illness
      in father or mother were 2.30 (95% CI 1.10-4.80), 1.56 (1.12-2.19), 4.75 (2.10
      10.8) and 1.73 (1.29-2.32), respectively. The strongest risk factor was mental
      illness in the adolescents themselves with risk ratios 33.1 (16.5-66.5), 24.3
      (6.64-88.7), 84.9 (7.17-1006) and 10.8 (7.75-15.0) for individuals hospitalised
      with schizophrenia, affective disorders, eating disorders or other psychiatric
      diagnoses and with an overall attributable risk of 15% (12-17%). The effect of
      parental socioeconomic variables decreased after adjustment for family history of
      mental illness. DISCUSSION: Important targets in youth suicide prevention could
      be to decrease the prevalence of or ameliorating the negative effects of
      psychiatric illness including early recognition and optimal treatment. Reports of
      high relative risk associated with parental low socioeconomic status may be
      confounded and overestimated if not adjusted for the association with mental
      disorder and suicide in the family.

PMID- 12523221
TI  - [Suicidal behavior in children--a descriptive study].
AB  - INTRODUCTION: Psychiatric illness and suicide attempts are important risk factors
      for suicide in young people. To what extent suicidal behaviour in childhood
      predicts suicidal behaviour and suicide later in life is not known, and studies
      concerning suicidal behaviour and psychopathology in children are limited. The
      objective of the study was to describe suicidal behaviour in children referred to
      child psychiatric assessment concerning the frequency and characteristics of the
      suicidal behaviour and the psychiatric diagnoses of the children. MATERIAL AND
      METHODS: Children under the age of 15 from the County of Copenhagen referred to
      child psychiatric ward because of suicidal behaviour. The period studied was
      January 1st 1998 to December 31st 2000. Data regarding the children were
      collected from a clinical database and medical records. Children seen at other
      wards by child psychiatric consultants have not been included in the descriptive
      part of the study. RESULTS: The incidence of referred children corresponds to a
      rate of suicidal behaviour of 63.0 per 100,000. A total of 126 children were
      referred. 62 were patients in a child psychiatric ward. Among these, 97% were
      diagnosed as having psychiatric problems. Children with suicidal risk made out 6%
      of all referred children. The ratio of boys to girls was 53:73. Most of the girls
      were aged 13-14 and the boys 8-12. Seven boys suffered from psychoses and
      pervasive developmental disorders, the rest of the boys from attention deficit
      and hyperactivity disorders and mixed disorders of conduct and emotions. The
      oldest girls were suffering from personality disorders. Poisoning was common
      among the girls and more violent self-destructive acts characterized the suicidal
      behaviour of the boys. DISCUSSION: Suicidal behaviour was associated with
      psychopathology in most children referred. Serious psychiatric disturbances as
      psychotic disorders were found in boys as young as seven years of age, and
      personality disorders were most common in the girls. Sex differences in suicidal
      behaviour known from studies of adolescents and adult people seem to be
      manifested early in childhood. PERSPECTIVES: Prospective studies are needed to
      clarify the association of psychopathology and suicidal behaviour in childhood
      and later suicidal behaviour and suicide.

PMID- 12523222
TI  - [Epilepsy surgery of Danish children 1996-2002].
AB  - INTRODUCTION: Epilepsy surgery is done in order to obtain seizure freedom or to
      reduce the number of epileptic seizures in selected patients not responding to
      medical treatment. Few Danish children have had this treatment, most probably
      because of some restrictions imposed by The Danish National Health Board. We
      present the results of the first 22 Danish children who have had epilepsy
      surgery. MATERIAL AND METHODS: All children up to the age of 15 operated from
      January 1st 1996 to May 1st 2002 are included. According to the guidelines of The
      Danish National Health Board, 17 children have been operated abroad because the
      epileptic focus was extratemporal or intracranial EEG-monitoring was necessary.
      Follow-up varied from five years and six months to one month. RESULTS: At the
      time of the operation, all children had a long-lasting medical intractable
      epilepsy. 18 children had daily seizures and 15 were mentally retarded. Multi
      lobar resection was performed in ten, hemispherectomy in three and lobar
      resection in eight children. Total seizure-free outcome was seen in 12 children,
      whereas three only had simple partial seizures (totally 68 per cent). The
      remaining children had at least a 50 per cent seizure reduction. On an average,
      the cognitive function was unchanged one year after the surgery. The majority of
      the parents stated that the behaviour of the child had improved on one or more
      specific issues. One mother stated that to a certain degree she regretted the
      operation. In four children, an unexpected complication was registered (slight
      hemiparesis and a hemianopsia). DISCUSSION: The results documented that epilepsy
      surgery is effective for selected children in spite of long-lasting severe
      epilepsy. In order to alleviate the consequences of severe epilepsy it is,
      however, important to refer the patients early. There seems to be a need for more
      and early referrals for childhood epilepsy surgery in Denmark.

PMID- 12523223
TI  - [Children's health at the 1,5-year examination in the municipality of Sundeved].
AB  - INTRODUCTION: We investigated whether the health visitor at an examination of
      children aged 18 months could identify those with an increased risk of morbidity
      and use of health services. METHODS: From 1992 to 1997, 233 children aged 18
      months were examined by the health visitor from the district of Sundeved,
      Denmark. At each examination, the visitor filled in a questionnaire concerning
      the child's health, living conditions, and development. RESULTS: Forty-one per
      cent of the children had been breast-fed for less than nine weeks. This
      percentage was highest in working class families and families outside the labour
      market. Nearly one third had a mother who smoked. Children whose mother smoked
      had a lower mean birth-weight than those with a non-smoking mother. The mother's
      smoking habits and age were also related to the duration of breast-feeding. Non
      smoking mothers and mothers above 30 years of age had breast-fed more weeks than
      mothers who smoked or were younger. Diseases such as ordinary colds, inflammation
      of the middle ear, and bronchitis were common. Seventy-two per cent of the
      children had been treated with antibiotics once or more, 28% had visited a
      specialist, and 26% had been to hospital once or more. DISCUSSION: Social factors
      are of great importance for the health of young children.

PMID- 12523225
TI  - [Chlamydia trachomatis and Neisseria gonorrhoeae infections in sexually abused
      children in Jutland].
AB  - INTRODUCTION: At the Department of Forensic Medicine, University of Aarhus,
      Denmark, examinations are performed of children who are suspected of having been
      sexually abused. The medical forensic investigation aims at documenting sexual
      abuse if there are any physical findings. The presence of certain sexually
      transmitted diseases, which cannot be explained otherwise, may be such
      documentation. This article focuses on Chlamydia trachomatis and Neisseria
      gonorrhoeae, and the risk for the sexually abused child to contract these
      diseases. MATERIAL AND METHODS: Retrospectively, we went through the Institute's
      files from 1996 to 2000 concerning child abuse. Information about age, sex,
      cultures for Chlamydia trachomatis and for Neisseria gonorrhoeae, and the results
      of these cultures was registered. If the child had been cultured, the suspected
      perpetrator's age and gender were registered as well. The children were all
      between 0 and 15 years of age, and in all cases the suspicion of sexual abuse had
      led to reporting to the police. RESULTS: 295 girls and 41 boys were examined in
      the period from 1996 to 2000. A total of 100 cultures for Chlamydia trachomatis
      and 105 cultures for Neisseria gonorrhoeae were performed. Among the 111 children
      who were examined for Chlamydia trachomatis and/or Neisseria gonorrhoeae there
      were no positive results. In 102 cases the suspected perpetrator was known to be
      one or more men, and only in one case it was a women. The mean age of the
      suspected perpetrators was 35.4 years. DISCUSSION: The prevalence of Neisseria
      gonorrhoeae and Chlamydia trachomatis should reflect the prevalence in the group
      of perpetrators. Neisseria gonorrhoeae is uncommon outside Copenhagen, the
      capital of Denmark, whereas Chlamydia trachomatis is quite common. On this
      background, we had expected some of the children to be infected with Chlamydia
      trachomatis. Therefore, the risk for sexually abused children to be infected with
      Chlamydia trachomatis or Neisseria gonorrhoeae is very low, depending on the kind
      of abuse and the perpetrator's possible risk behaviour, age, and gender. As a
      conclusion, only children with a clear indication should be tested for these
      sexually transmitted diseases.

PMID- 12523224
TI  - [Beta-thalassemia major in children and adolescents in Denmark].
AB  - INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among
      Danish children as a result of immigration. The aim of the study was to estimate
      the occurrence of beta-thalassemia major in Denmark, analyse the treatment and
      organ functions, and identify areas for an improved treatment strategy. MATERIAL
      AND METHODS: During 1998-99 all Danish pediatric departments were contacted for
      identification of children aged 0-18 years with beta-thalassemia major. Blood
      transfusions and chelation therapy were registered, and for Eastern Denmark
      clinical, endocrine, cardiac, and serologic parameters were performed. RESULTS:
      Twenty-six children had beta-thalassemia major. Out of these, 20 received blood
      transfusions, and 17 patients were chelated. Eight patients were not chelated
      owing to previous bone marrow transplantation, treatment with hydroxyurea or
      ferritin < 2000 micrograms/l and young age. One patient had died. The body height
      was between 1.5 and -5.4 SDS (median -1.7) and the sitting height was -0.6 to 
      5.6 SDS (median -2.3). The bone age was delayed 1-5 years (median -2.5) in six
      out of ten examined patients, and puberty delayed in four out of five. A dilated
      left ventricle was documented in one out of eight patients examined. All patients
      were HIV and hepatitis C negative. For 75% of the children, the parents were
      related. DISCUSSION: Children and adolescents with beta-thalassemia major in
      Denmark experience major heterogenicity with regard to treatment and late
      effects. An earlier and more effective iron chelation therapy together with
      improved patient support may reduce growth disturbances and endocrine and cardiac
      late effects.

PMID- 12523226
TI  - [Chronic inflammatory bowel disease in children. An epidemiological study from
      eastern Denmark 1998-2000].
AB  - INTRODUCTION: The purpose of this retrospective study was to investigate the
      epidemiology and anthropometrical status in children and adolescents with chronic
      inflammatory bowel disease in Denmark during the period 1998-2000. MATERIAL AND
      METHODS: Patients from the eastern part of Denmark below 15 years of age were
      included. The study covered 43% of the total pediatric population (< 15 years) in
      Denmark. Data from the patient records were used to register diagnosis, area of
      living, age when presenting symptoms, age at diagnosis, height, weight, and
      disease location for Crohn's disease at the time of the diagnosis. RESULTS: A
      total of 98 patients < 15 years with inflammatory bowel disease were identified
      in the period 1998-2000. Fifty patients had ulcerative colitis, 44 had Crohn's
      disease, and four had indeterminate colitis. The mean annual incidence of
      inflammatory bowel disease was 4.3 (1.8 for ulcerative colitis, 2.3 for Crohn's
      disease, and 0.2 for indeterminate colitis) per 100,000 children < 15 years. The
      mean annual prevalence of inflammatory bowel disease was 15.8 per 100,000
      children < 15 years (ulcerative colitis: 8.3; Crohn's disease: 6.7; indeterminate
      colitis: 0.8). A subpopulation of Crohn's disease patients with growth
      retardation was found. Undernutrition was also common among children with Crohn's
      disease. Eighty-three percent had an age-related BMI below the 50-percentile.
      DISCUSSION: Compared to an earlier Danish investigation, the incidence of Crohn's
      disease had risen 11-fold whereas the incidence of ulcerative colitis remained at
      the same level. The subpopulation with growth failure and low age-related BMI
      among children with Crohn's disease is in line with data described in the
      literature.

PMID- 12523227
TI  - [An outbreak of tinea capitis in a child care center].
AB  - We describe an outbreak of tinea capitis in a kindergarten. Individuals with
      relation to the institution were examined clinically and mycologically (n = 98).
      Microsporum audouinii was cultured from 12 people, out of whom eight patients had
      tinea capitis and seven patients had tinea corporis. Three patients had both
      tinea capitis and tinea corporis. The problems with spread of anthropophilic
      infections and the difficulties with treatment of Microsporum dermatophytes are
      discussed.

PMID- 12523228
TI  - [Quality of antibodies and somatic hypermutation].

PMID- 12523229
TI  - [Miscalculation or what?].

PMID- 12523230
TI  - [Attention deficit disorder with hyperactivity and DAMP in children].

PMID- 12523231
TI  - [Obesity epidemic after Letigen].

PMID- 12523232
TI  - Safe or disastrous?

PMID- 12523233
TI  - Adjustable surgical screwdriver.

PMID- 12523234
TI  - Poor science.

PMID- 12523235
TI  - Oral and maxillofacial radiology gains ADA acceptance.

PMID- 12523236
TI  - There's nothing little about this campaign.

PMID- 12523237
TI  - Mice missing enzyme suffer dwarfism, thin bones, and arthritis.

PMID- 12523238
TI  - The Pankey Institute enters the new millennium. Interview by Phillip Bonner.

PMID- 12523239
TI  - Update in aesthetic tooth whitening for the new millennium.

PMID- 12523240
TI  - Aesthetics and periodontal complications: a way to aesthetically improve lost
      attachment with ceramic veneers.

PMID- 12523241
TI  - Shaping root canals, Part V: GT File technique in small-root canals.

PMID- 12523242
TI  - Thermal endodontic condensers: the warm lateral condensation technique.

PMID- 12523243
TI  - Ultraconservative resin restorations. "Watch and wait" is not acceptable
      treatment.
AB  - UltraConservative dentistry represents a great step forward for the dentist, the
      profession, and particularly for the patient. It involves the early detection and
      complete elimination of all accessible and non-accessible carious material from
      the tooth. Untreated caries, though they may be tiny, can be extremely and very
      rapidly destructive. The earliest interception of decay maintains total dental
      health, and increases the likelihood of the restored teeth lasting a lifetime.

PMID- 12523244
TI  - Helping people change, Part 2: The magic of motivation.
AB  - The consensus of the data and the interviewed doctors was that the five most
      profound motivators of people in the workplace today include the following:
      achievement of well-done work; personal pride and satisfaction in being a part of
      quality treatment and excellent care of patients; continuing education; respect,
      responsibility, and appreciation; and equitable compensation. "Motivation is the
      most critical factor in the productivity of my practice," said Dr. Stelly.
      "Motivation is the key. If everyone is on the same page and the doctor and key
      team members can continue to motivate and encourage others, then the sky is the
      limit. The key is to keep everyone goal oriented, unified, and excited about the
      possibilities."

PMID- 12523246
TI  - Menu and workout makeovers. New diet and exercise  guidelines bend previous
      rules.

PMID- 12523245
TI  - The virtual operatory: roundtable on operatory computerization, ergonomics, and
      equipment. Interview by Cheryl Farr.

PMID- 12523247
TI  - Aspirin or warfarin: what's best after a heart attack? Risk of bleeding counters
      warfarin's edge in efficacy.

PMID- 12523248
TI  - Managing MS. While a cure is sought, people with MS can help themselves.

PMID- 12523249
TI  - Prostate cancer: wait or treat? How to apply new findings to your individual
      situation.

PMID- 12523250
TI  - Task force recommends osteoporosis screening.

PMID- 12523251
TI  - Stretching: pain and no gain?

PMID- 12523252
TI  - Lifestyle affects risk of two brain disorders.

PMID- 12523253
TI  - Home exercise helps the frail and elderly.

PMID- 12523254
TI  - Whole grains cut diabetes risk.

PMID- 12523255
TI  - Wart worries? Try salicylic acid.

PMID- 12523256
TI  - Splitting pills OK in certain cases.

PMID- 12523257
TI  - I have elevated levels of C-reactive protein. How does that affect my risk of
      developing heart disease?

PMID- 12523258
TI  - I read that nearly a quarter of adult Americans have "metabolic syndrome". What
      is this malady, and how can I prevent it?

PMID- 12523259
TI  - Stalking syndrome X.

PMID- 12523260
TI  - Lifesaving answers from exercise stress testing.

PMID- 12523261
TI  - Viagra: a blueprint for safety and reliability.

PMID- 12523262
TI  - Harnessing the anticancer power of plants.

PMID- 12523263
TI  - Is it OK for me to split my pills to save money on medications?

PMID- 12523264
TI  - Will I live a longer, healthier life if I radically reduce my calorie intake?

PMID- 12523265
TI  - Folate delivers head-to-toe health advantages. The B vitamin that benefits unborn
      babies may also protect the hearts and minds (and colons) of adults.

PMID- 12523266
TI  - Catching skin cancer early. New treatments aim to keep keratoses from developing
      into invasive cancer.

PMID- 12523267
TI  - Hysterectomy options. Total and subtotal surgical procedures prove comparable.

PMID- 12523268
TI  - Salt shakedown. DASH diet beats salt restriction at lowering blood pressure.

PMID- 12523269
TI  - Breast self-exams: still worth the effort?

PMID- 12523270
TI  - Give antidepressants at least six months.

PMID- 12523271
TI  - Breast cancer surgeries compared.

PMID- 12523272
TI  - Delaying glaucoma.

PMID- 12523273
TI  - Questions and answers. I'm trying to become pregnant. Should I avoid my two cats
      (and their litter box) to lower my risk of toxoplasmosis?

PMID- 12523274
TI  - Questions and answers. How do I know if I need a tetanus shot?

PMID- 12523275
TI  - Is there a link between MMR vaccine and autism?...and an expert's commentary.

PMID- 12523276
TI  - Protecting children from the flu: the flu vaccine is one way...and there's
      handwashing.

PMID- 12523277
TI  - Tips for EpiPen.

PMID- 12523278
TI  - What to do about a child who bites?

PMID- 12523279
TI  - Treating warts: is duct tape the answer?

PMID- 12523280
TI  - FDA consolidates review process for new pharmaceuticals.

PMID- 12523281
TI  - CDC helps in battle against West Nile virus.

PMID- 12523282
TI  - Contaminated honey imports.

PMID- 12523283
TI  - FDA initiative will enhance drug good manufacturing practices.

PMID- 12523285
TI  - FDA and FSIS issue Listeria health advisory.

PMID- 12523284
TI  - New treatment approved for chronic hepatitis B.

PMID- 12523286
TI  - Recall of gonorrhea test kits.

PMID- 12523288
TI  - FDA expert named first 'Americas Fellow'.

PMID- 12523287
TI  - GlucoWatch approved for children with diabetes.

PMID- 12523289
TI  - New light therapy for acne.

PMID- 12523290
TI  - Study: improvements in safe food handling by consumers.

PMID- 12523291
TI  - Mayo clinic study: optimists report higher quality of life.

PMID- 12523292
TI  - 'Virtual stomach' reveals pill's path.

PMID- 12523293
TI  - Oxygen bars: is a breath of fresh air worth it?

PMID- 12523294
TI  - The 'Poison Squad' and the advent of food and drug regulation.

PMID- 12523295
TI  - How well are your sleeping?

PMID- 12523296
TI  - Think it through: a guide to managing the benefits and risks of medicines.

PMID- 12523297
TI  - Sunning for science. The effects of common substances on sun-exposed skin.

PMID- 12523298
TI  - Plastics and the microwave.

PMID- 12523299
TI  - Public affairs specialists: on the FDA's front line.

PMID- 12523300
TI  - Dairy owners charged with milking customers.

PMID- 12523301
TI  - The FDA's public affairs specialists: making a difference.

PMID- 12523302
TI  - The value of HIV peer education programs in correctional facilities.

PMID- 12523303
TI  - Interview. HIV Inside spoke with Suzanne Bailey, Medical and Health Education
      Coordinator for the Florida Department of Corrections, which recently expanded
      its peer education program.

PMID- 12523304
TI  - The wisdom of the receptors: neuropeptides, the emotions, and bodymind. 1986.

PMID- 12523305
TI  - Bilateral maxillary fourth molars and a supernumerary tooth in maxillary canine
      region--a case report.
AB  - The occurrence of supernumerary teeth is a relatively uncommon dental anomaly.
      The aetiology is not clear. Supernumerary teeth have frequently been observed as
      solitary teeth and impacted in the maxillary arch. This case report describes the
      rare presence of bilateral maxillary fourth molars and a supernumerary tooth in
      the maxillary canine region. On the left side, the third molar was extracted
      first, allowing the fourth molar to move into a more favourable position for
      later extraction. Two-year postoperative radiography confirmed that the
      supernumerary tooth had migrated occlusally and mesially permitting a safer
      extraction procedure.

PMID- 12523306
TI  - Prostatectomy or watchful waiting in prostate cancer.

PMID- 12523307
TI  - Prostatectomy or watchful waiting in prostate cancer.

PMID- 12523308
TI  - Prostatectomy or watchful waiting in prostate cancer.

PMID- 12523309
TI  - Prostatectomy or watchful waiting in prostate cancer.

PMID- 12523310
TI  - Endotoxin and asthma.

PMID- 12523312
TI  - Bibliography. Current world literature. Vasculitic syndromes.

PMID- 12523311
TI  - Endotoxin and asthma.

PMID- 12523313
TI  - Bibliography. Current world literature. Systemic disorders with rheumatic
      manifestations.

PMID- 12523314
TI  - Mammographic density of the breast.

PMID- 12523315
TI  - Bibliography. Current world literature. Hypertrophic osteoarthropathy.

PMID- 12523316
TI  - Statement of the American Academy of Nursing and the American Organization of
      Nurse Executives for the Food and Drug Administration regarding bar code labeling
      for human drug products.

PMID- 12523317
TI  - QIPMO: an innovation to improve quality in long-term care. The Quality
      Improvement Program of Missouri.

PMID- 12523318
TI  - Reflections of the editor. 1954.

PMID- 12523319
TI  - Current readings in nuclear medicine.

PMID- 12523320
TI  - Overview of clinical PET.

PMID- 12523321
TI  - Recent publications in hematological oncology.

PMID- 12523322
TI  - Torsion of the appendix.

PMID- 12523323
TI  - Care in the chicken coop.

PMID- 12523324
TI  - The importance of metabolic rate and the folly of body surface area calculations.
AB  - Mathematical formulae to calculate body surface area from measurements of height,
      weight and other parameters date from the late 19th century. Drug doses, fluid
      therapy, caloric requirements and physiological parameters such as cardiac
      output, glomerular filtration rate and a variety of respiratory function
      parameters are all frequently expressed in terms of a body surface area. Body
      surface area is often used in preference to body mass (weight). However, the
      original rationale for using body surface area as an estimate for metabolic rate
      has never been tested and the algorithms used to approximate body surface area
      have little evidence to support their use in this role. Recent developments in
      technology using indirect calorimetry allow easy measurement of metabolic rate in
      the clinical setting. Such measurements should be used for standardisation when
      weight alone is considered inadequate.

PMID- 12523325
TI  - A study of the impact of long-term tobacco smoking on postoperative intensive
      care admission.
AB  - Smoking is a risk factor for intra-operative pulmonary complications and a wide
      range of postoperative pulmonary, cardiovascular, infection and wound-related
      complications. These may all lead to unplanned postoperative intensive care
      admission. We tested the hypothesis that smokers have an increased incidence of
      postoperative intensive care admission and more postoperative complications than
      nonsmokers in a general and orthopaedic surgical population. The following
      information was assessed in 6026 surgical patients: age, sex and smoking status
      (pack-years), history of heart and lung disease, American Society of
      Anesthesiologists (ASA) physical classification, intensive care admission and
      postoperative complications. Two thousand five hundred and twenty-six (46%) were
      smokers but for 620 patients (10.3%) smoking status was not confirmed.
      Postoperative intensive care admission was required by 319 patients (5.3%).
      Patients with > 50 pack-years were admitted to the intensive care more frequently
      than were smokers with < or = 50 pack-years history and nonsmokers (p < 0.001).
      Ex-smokers with > 50 pack-years history had the same risk of postoperative
      admission to intensive care as smokers with > 50 pack-years history. Smokers
      admitted to intensive care with > 50 pack-years history had a higher incidence of
      chronic lung disease (p < 0.005) and heavy alcohol consumption (p < 0.001). These
      smokers also had a higher incidence of postoperative pulmonary complications
      (odds ratio = 3.91, p < 0.01). The mortality rate was 37% in smokers with > 50
      pack-years history and 24% in nonsmokers (odds ratio = 2.02, p = 0.08). We
      conclude long-term tobacco smoking (> 50 pack-years) carries a higher risk of
      postoperative admission to intensive care, and there seems to be a dose
      relationship between the amount of tobacco consumed and the risk of postoperative
      intensive care admission.

PMID- 12523326
TI  - The effect of neuromuscular blockade on the efficiency of mask ventilation of the
      lungs.
AB  - We conducted a two-part study to assess the practice of withholding neuromuscular
      blockade until the ability to ventilate the lungs using a bag and face mask (mask
      ventilation) has been established following induction of anaesthesia. The first
      part of the study consisted of a postal survey (71% response rate) of 188
      anaesthetists in the Oxford region to assess their current practice. Thirty per
      cent of respondents always checked mask ventilation before administering a
      neuromuscular blocking drug, whereas 39% of respondents (all them consultants)
      never did this. A further 31% only did so in the case of known or anticipated
      difficulty with the airway. In the second part of the study, we measured inspired
      (V(TI)) and expired (V(TE)) tidal volumes before and after neuromuscular blockade
      in 30 patients undergoing general anaesthesia. The ratio V(TE)/V(TI) was used as
      a measure of the efficiency of ventilation. There was no difference in
      V(TE)/V(TI) before [mean (SD) 0.47 (0.13)] and after [0.45 (0.13)] neuromuscular
      blockade. We conclude that neuromuscular blockade does not affect the efficiency
      of mask ventilation in patients with normal airways.

PMID- 12523327
TI  - The effect of intra-operative video on patient anxiety.
AB  - We conducted a randomised controlled study to evaluate whether watching video
      compact discs intra-operatively using a liquid crystal display (LCD) unit
      decreased anxiety. Forty-four patients undergoing elective surgery under regional
      anaesthesia were assigned to either the LCD or control group. Anxiety was
      measured using the Chinese version of the State-Trait Anxiety Inventory (STAI)
      and visual analogue score (VAS). The mean (SD) anxiety trait scores were 46.15
      (6.28) and 46.40 (7.32) in the control and LCD groups, respectively. The state
      anxiety of the LCD group [35.50 (7.96)] measured immediately postoperatively was
      significantly lower than the control group [41.50 (9.02); p = 0.03]. The median
      (range) reduction in VAS anxiety score was not significantly greater in the LCD
      group [20 (20 to 80) mm] compared with the control group [12.5 (70 to 60) mm].
      Watching video intra-operatively reduces patient anxiety as measured by the STAI.

PMID- 12523328
TI  - Plasma paracetamol concentrations after different doses of rectal paracetamol in
      older children A comparison of 1 g vs. 40 mg x kg(-1).
AB  - We compared the plasma paracetamol levels attained after the administration of
      different doses of rectal paracetamol in healthy children to see if they attained
      therapeutic levels (> 10 microg x ml(-1)). We recruited 24 children (ASA I-III)
      over 25 kg undergoing elective surgery. They were randomly assigned to receive
      rectal paracetamol at a dose of 1 g or 40 mg x kg(-1). Blood samples were taken
      for analysis at 2, 3, 4 and 5 h post dose. Most children in the 1 g group failed
      to attain therapeutic plasma levels, whereas those in the 40 mg kg(-1) group did
      achieve therapeutic levels (mean maximum concentration = 7.8 vs. 15.9 microg x
      ml(-1), p = 0.009).

PMID- 12523329
TI  - 'Airway Alerts'. How UK anaesthetists organise, document and communicate
      difficult airway management.
AB  - A questionnaire on organisation, documentation and communication of airway
      problems during anaesthesia was sent to 271 anaesthetic college tutors in the UK.
      Their responses were compared with three published recommendations. There was a
      72% response rate (195/271). The recommendations of the American Society of
      Anaesthesiologists Task Force on the Management of the Difficult Airway were met
      by 71% of respondents; 2% met those suggested by the Canadian Airway Focus Group
      and 2% met those suggested in a standard UK textbook on difficulties in tracheal
      intubation. Guidelines for management of the difficult airway were available in
      142 departments (73%), but only 41 (21%) had guidelines for communication and
      dissemination of information. We present an 'Airway Alert' scheme which has since
      been adopted by the Difficult Airway Society.

PMID- 12523330
TI  - Changes in cerebral oxygenation in children undergoing surgical repair of
      ventricular septal defects.
AB  - There have been few published studies on changes in cerebral oxygenation during
      paediatric cardiac surgery as measured by conventional near-infrared
      spectroscopy. We studied changes in cerebral oxygenation in 16 children
      undergoing surgical repair of ventricular septal defects. Fifteen of the patients
      showed similar patterns of changes: brain tissue concentrations of oxyhaemoglobin
      decreased significantly during cardiopulmonary bypass, whereas there was no
      significant change in brain tissue concentrations of deoxyhaemoglobin. In the
      remaining patient, who suffered decreased blood flow to the lower body during
      surgery, the pattern of changes was different to that of the other subjects. This
      patient suffered postoperative respiratory and renal failure. This study suggests
      that conventional near-infrared spectroscopy may be useful for clinical
      monitoring during ventricular septal defect repair.

PMID- 12523332
TI  - Medicine and sport.

PMID- 12523333
TI  - From the Centers for Disease Control and Prevention. Outbreaks of gastroenteritis
      associated with noroviruses on cruise ships--United States, 2002.

PMID- 12523334
TI  - From the Centers for Disease Control and Prevention. Involvement by young drivers
      in fatal alcohol-related motor-vehicle crashes--United States, 1982-2001.

PMID- 12523335
TI  - From the Centers for Disease Control and Prevention. Occupational health
      indicators for tracking work-related health effects and their determinants.

PMID- 12523336
TI  - Financial incentives and drug spending in managed care.
AB  - Pharmaceutical costs have been rising dramatically since 1995, growing 16.6% in
      1998 alone. This rate of increase is more than four times that of all health care
      spending. Employers, managed care organizations and consumers are looking anew
      for ways to stem these rising costs, without denying patients effective care.
      Therefore, this Issue Brief is especially timely because it investigates how
      patient copayments and financial incentives for physicians affect drug spending
      in managed care.

PMID- 12523337
TI  - Bibliography. Current world literature. Therapy and clinical trials.

PMID- 12523338
TI  - Colorectal cancer screening with sigmoidoscopy: primary care issues.
AB  - Colorectal cancer is the second leading cause of death from cancer in the U.S.,
      behind lung cancer. Numerous medical societies recommend routine screening for
      colorectal cancer with flexible sigmoidoscopy for people 50 and over. But who
      will perform the procedure, and who will pay for it? The case of flexible
      sigmoidoscopy illustrates the economic and practical issues of introducing a
      screening procedure into primary care practice. This Issue Brief investigates the
      role of primary care physicians in providing this service as part of routine
      care, and identifies attitudinal and financial barriers to overcome.

PMID- 12523339
TI  - Organization and outcomes of inpatient AIDS care.
AB  - The establishment of AIDS hospitals and AIDS units within hospitals has been
      controversial. Unlike other specialty care, AIDS care arrangements were initially
      developed as much to segregate AIDS patients from other patients and staff as to
      provide the best possible care. Ten years after many of these units opened,
      little evidence was available about whether the benefits of aggregating AIDS
      patients outweighed the potential hazards of segregating people from the
      mainstream of hospital care. This Issue Brief describes a national study to
      determine how different organizational settings affect the outcomes of inpatient
      AIDS care.

PMID- 12523340
TI  - Managed competition: lessons from Britain.
AB  - As phrases like "managed care backlash" become part of the lexicon in American
      health care policy circles, it is instructive to examine a managed competition
      experiment in a vastly different context. Britain's Conservative government
      instituted reforms in 1991 to transform the National Health Service (NHS) from a
      centrally administered service to managed competition between purchasers and
      providers. Five years later, it replaced those reforms to promote cooperation
      rather than competition. This Issue Brief summarizes what the NHS can learn from
      decades of American experience with purchasing care, and what the American health
      system can learn from the British experiment with an internal market in the
      1990s.

PMID- 12523341
TI  - Sale of prescription drugs over the Internet.
AB  - Online drugstores represent one of the hottest categories in electronic commerce.
      The Internet offers great promise in expanding access to prescription drugs for
      the disabled, the elderly, and people living in rural areas. But with this
      promise comes the danger of eliminating the safeguards that protect consumers
      from inappropriate use of medications and adverse drug events. This Issue Brief
      highlights two studies that investigate the availability of prescription drugs
      over the Internet, and focuses on the alarming ease with which consumers can
      obtain drugs without seeing a physician or a pharmacist.

PMID- 12523342
TI  - Violent injuries among women in an urban area.
AB  - The national statistics are familiar by now: each year, more than 2 million women
      are raped and/or physically assaulted; more than one-third of them are injured
      during their most recent assault. Annually, more than 500,000 women seek medical
      services as a result of violence-related injuries, often from hospital emergency
      departments. But national statistics cannot fully capture the extent of violence
      experienced by women in inner-city areas, nor do they point to modifiable risk
      factors at a community level. This Issue Brief highlights a new study that
      investigates the circumstances and correlates of violent injuries among women in
      one urban, low-income community.

PMID- 12523343
TI  - Lessons from the Allegheny bankruptcy.
AB  - On July 21, 1998, the nonprofit Allegheny Health, Education, and Research
      Foundation (AHERF) filed for bankruptcy, with $1.3 billion in debt and 65,000
      creditors. The Pittsburgh-based organization had pursued an aggressive strategy
      of acquiring physicians and hospitals in the Philadelphia area. Its dramatic
      collapse prompted the entry of a for-profit hospital chain into the Philadelphia
      market, as Tenet Healthcare Corp. purchased eight hospitals from AHERF at
      firesale prices. This Issue Brief chronicles the hows and whys of the nation's
      largest nonprofit health care failure, and analyzes its lessons for other
      struggling academic health centers.

PMID- 12523344
TI  - Genetic testing for breast and ovarian cancer: implications for life insurance.
AB  - As the science of genetic testing progresses, the debate surrounding the uses of
      genetic information intensifies. In February, President Clinton signed an
      executive order prohibiting federal agencies from using such information to make
      hiring, promotion, or placement decisions. Concerns about privacy and
      discrimination have led many states to propose or enact statutes that prohibit
      health insurers from using genetic test results in their underwriting decisions.
      However, few statutes address access to these results by the life insurance
      industry. This Issue Brief summarizes the current debate on whether life insurers
      should have access to genetic testing information for breast and ovarian cancer,
      and provides actuarial insight into the potential effect of such testing on the
      voluntary term insurance market.

PMID- 12523345
TI  - Children's mental health: recommendations for research, practice and policy.
AB  - A recent study documented a large increase in prescriptions of stimulants and
      antidepressants among preschoolers, and has prompted public and professional
      concern about the effects of mood-altering drugs on young children. In response,
      the White House announced a broad initiative on children's mental health,
      including more government money for research, new labels on drugs for pediatric
      use, educational materials for parents, and a fall White House conference. To
      place these events in their larger context, this Issue Brief summarizes the
      findings of the Children's Mental Health Alliance Project, which conducted a
      multidisciplinary consensus conference in November 1998 followed by a year-long
      dialogue with clinicians, researchers, and families.

PMID- 12523346
TI  - Physician responses to the marketplace: group practices and hospital alliances.
AB  - Congress is now debating legislation that would give independent physicians the
      right to bargain collectively with managed care organizations. Proponents argue
      that this legislation is needed to counterbalance the market power of managed
      care organizations; opponents argue that physicians can already gain leverage and
      negotiating strength by forming group practices or through joint ventures with
      hospitals. This debate has brought attention to the competitive nature of the
      health care marketplace, and physician responses to managed care. This Issue
      Brief examines how physicians are reorganizing their practices to meet the
      demands of the competitive marketplace.

PMID- 12523347
TI  - When "buckle up" is not enough: enhancing the safety of children in motor
      vehicles.
AB  - Motor vehicle crashes are the leading cause of death and acquired disability in
      children over age 1 in the United States. In 1998 alone, 697 children under age 6
      died as occupants in motor vehicles, and nearly 100,000 were injured. This Issue
      Brief describes findings from Partners for Child Passenger Safety, the nation's
      largest surveillance system of children in car crashes, and points to
      improvements in child restraints that can reduce the risk of serious injury in
      the event of a crash.

PMID- 12523348
TI  - Idiopathic giant esophageal ulcer in an HIV-positive child.
AB  - We report a 3-year old HIV-positive female with a 2-cm deep ulcer in the mid
      esophagus. A presumptive diagnosis of idiopathic giant ulcer was made after
      infectious pathogens had been excluded. The child was successfully treated with
      steroids. Although infectious causes of giant esophageal ulcers in HIV-positive
      children are common, the diagnosis of idiopathic giant ulcer must be considered
      in order to institute proper therapy.

PMID- 12523349
TI  - Kyphomelic dysplasia, phenotypic variability and presence of a caudal appendage.

PMID- 12523350
TI  - Pathological correlation of CT-detected mediastinal lymphadenopathy in children:
      the lack of size threshold criteria for abnormality.

PMID- 12523351
TI  - Natural TWIST protein variants in a panel of eleven non-human primates: possible
      implications of TWIST gene-tree for primate species tree.
AB  - The twist gene is implied in head morphogenesis, as human patients heterozygous
      at TWIST and heterozygous M-twist mutant mice present similar cranial-facial
      abnormalities. M-twist and TWIST are respectively unique genes, coding for a B
      HLH transcription factor. We identified twist coding sequences from 11 species
      representing 7 families of primates, report their conservation and genus-specific
      amino acid substitutions, and present a tentative gene-tree of these sequences.
      Amino acid changes result in natural Twist variants, which might contribute to
      generating distinct head morphologies in species. These data suggest twist as a
      molecular marker, which could be used to refine controversial classification.

PMID- 12523353
TI  - Medicare and Medicaid programs; fire safety requirements for certain health care
      facilities. Final rule.
AB  - This final rule amends the fire safety standards for hospitals, long-term care
      facilities, intermediate care facilities for the mentally retarded, ambulatory
      surgery centers, hospices that provide inpatient services, religious nonmedical
      health care institutions, critical access hospitals, and Programs of All
      Inclusive Care for the Elderly facilities. Further, this final rule adopts the
      2000 edition of the Life Safety Code and eliminates references in our regulations
      to all earlier editions.

PMID- 12523352
TI  - [Purification and kinetic parameters of a Streptomyces olivaceoviridis protein
      which binds N-acetylglucosamine and chitin oligomers].
AB  - A specific substrate binding protein is located within the membrane of
      Streptomyces olivaceoviridis mycelia. After Triton extraction of the membrane,
      two forms of the protein (46.0 kD and 47.5 kD) were purified to apparent
      homogeneity by consecutive anionic exchange chromatographies. The results of
      competition interacted with N-acetylglucosamine and chitin oligomers (C2 to C6),
      but not with cellobiose nor glucose. Using surface plasmon resonance, the kinetic
      parameters of the 46 kD form of the binding protein were determined. This protein
      showed a very high affinity for N-acetylglucosamine (K(d) = 8.29 x 10(-9) mol/L)
      and for chitobiose (K(d) = 3.81 X 10(-6) mol/L), and the lowest one was for
      chitotriose (K(d) = 1.95 X 10(-5) mol/L). Comparisons of the dissociation and
      association rate constants indicated that the interaction of this protein with
      each ligand was controlled by the association rate. N terminal sequence indicated
      that this protein might belong to an ABC transporter system.

PMID- 12523354
TI  - To the rescue: optimally locating trauma hospitals and helicopters.
AB  - Injury (trauma) is the leading cause of death in the United States for people
      younger than 45 years of age. Each day, more than 170,000 men, women, and
      children are injured severely enough to seek medical care. About 400 of these
      people will die and another 200 will sustain a long-term disability as a result
      of their injuries. An estimated 20-40% of trauma-related deaths could be
      prevented if all Americans lived in communities that were served by a well
      organized system of trauma care. This Issue Brief describes a new computer model
      that can help State and regional policymakers decide where to place designated
      trauma hospitals and helicopter depots to maximize their residents' access to
      trauma care.

PMID- 12523355
TI  - New treatments for CNV secondary to AMD: what evidence exists to supports a
      treatment recommendation?

PMID- 12523356
TI  - Kehr's sign - a rare cause: spontaneous phrenic artery rupture.

PMID- 12523357
TI  - Revisiting nuclear power plant safety.

PMID- 12523358
TI  - Revisiting nuclear power plant safety.

PMID- 12523359
TI  - Punctual and canalicular agenesis presented with congenital nasolacrimal duct
      obstruction.

PMID- 12523360
TI  - Revisiting nuclear power plant safety.

PMID- 12523361
TI  - Value and application of the ICF in rehabilitation medicine.
AB  - CONTEXT: Rehabilitation medicine may be defined as the multi- and
      interdisciplinary management of a person's functioning and health. Rehabilitation
      medicine defines itself with respect to concepts of functioning, disability and
      health. Assessment and intervention management rely on these concepts. The
      current framework of disability--the WHO International Classification of
      Functioning, Disability and Health (ICF)--providing a coherent view of health
      from a biological, individual and social perspective. ISSUE: However, ICF success
      will depend on its compatibility with measures used in rehabilitation and on the
      improvement of its practicability. Thus, it is expected to see the development of
      the ICF based on versions of currently used instruments and on the development of
      ICF core sets. CONCLUSION: The new language ICF is an exciting landmark event for
      rehabilitation. It may lead to a stronger position of rehabilitation within the
      medical community, change multi-professional communication and improve
      communication between patients and rehabilitation professionals.

PMID- 12523362
TI  - Why courts cannot deny ADA protection to plaintiffs who do not use available
      mitigating measures for their impairments.
AB  - Congress intended the Americans with Disabilities Act ("ADA") to provide strong
      standards for addressing and eliminating discrimination against individuals with
      disabilities. Many commentators have concluded, however, that the federal courts
      are undermining the goals of the ADA by too narrowly construing membership in the
      statute's protected class. One example of this trend is courts' hostile treatment
      of ADA plaintiffs who do not use medications or devices that might alleviate
      their impairments ("nonmitigating plaintiffs"). Numerous district and appellate
      decisions have held or suggested that nonmitigating plaintiffs are not protected
      by the ADA. In addition, some commentators have proposed that courts should
      evaluate the reasonableness of a plaintiff's decision not to use mitigating
      measures; they argues that it is unfair to burden an employer with the cost of
      accommodating a disability that continues to exist only because an employee
      unreasonably refuses to mitigate it. Contrary to the views of these courts and
      commentators, however, this Comment will show that nonmitigating plaintiffs are
      entitled to ADA protection from employment discrimination. It argues that the
      statute's language, history, and structure, as well as Supreme Court precedent,
      demonstrate that courts cannot deny ADA protection based on a plaintiff's nonuse
      of available mitigating measures. It also presents several considerations that
      weigh against any future congressional enactment that would tie ADA protection to
      the reasonableness of a plaintiff's decision not to mitigate an impairment.

PMID- 12523363
TI  - Redressing wounds: finding a legal framework to remedy racial disparities in
      medical care.
AB  - In recent years, numerous medical studies and reports have documented startling
      disparities between the health status of African Americans and White Americans.
      The literature is replete with evidence that one of the main causes of these
      racial disparities is the different treatment of patients of different racial
      groups. This Comment addresses the possibility that implicit cognitive bias, in
      the form of implicit attitudes and stereotypes, significantly contributes to
      these racial disparities in medical treatment. Finding existing legal frameworks
      inadequate to address current disparities in health care, this Comment recommends
      avenues for the reworking of Title VI of the Civil Rights Act of 1964.
      Specifically, it suggests that disparate-treatment provisions that encompass
      claims arising from unintentional discrimination should be incorporated into
      Title VI, and it offers the employment law frameworks of Title VII and the Age
      Discrimination in Employment Act as models for such reform.

PMID- 12523364
TI  - From hospital to drugstore: insurance and the shift to outpatient care.
AB  - As policymakers consider whether and how to add prescription drug coverage to
      Medicare, they need to understand the relationship between insurance coverage and
      the adoption of new medical technologies, including drugs. Even the direction of
      these relationships is not always so clear. In this Issue Brief, Drs. Danzon and
      Pauly examine the shift from inpatient to outpatient care in the last 20
      years,and ask two broad questions: to what extent was this shift encouraged by
      changes in insurance, and to what extent was insurance coverage influenced by
      this shift?

PMID- 12523365
TI  - Isothermal strand-displacement amplification applications for high-throughput
      genomics.
AB  - Amplification of source DNA is a nearly universal requirement for molecular
      biology applications. The primary methods currently available to researchers are
      limited to in vivo amplification in Escherichia coli hosts and the polymerase
      chain reaction. Rolling-circle DNA replication is a well-known method for
      synthesis of phage genomes and recently has been applied as rolling circle
      amplification (RCA) of specific target sequences as well as circular vectors used
      in cloning. Here, we demonstrate that RCA using random hexamer primers with 29
      DNA polymerase can be used for strand-displacement amplification of different
      vector constructs containing a variety of insert sizes to produce consistently
      uniform template for end-sequencing reactions. We show this procedure to be
      especially effective in a high-throughput plasmid production sequencing process.
      In addition, we demonstrate that whole bacterial genomes can be effectively
      amplified from cells or small amounts of purified genomic DNA without apparent
      bias for use in downstream applications, including whole genome shotgun
      sequencing.

PMID- 12523366
TI  - Improving handwashing in hospitals: a patient education and empowerment program.
AB  - Each year, about 5% of people admitted to U.S. hospitals (about 2 million people)
      acquire an infection there. These infections cause nearly 20,000 deaths each
      year, and cost an estimated $4.5 billion to treat. Handwashing is the single most
      effective measure for preventing hospital-acquired infections. Despite widespread
      knowledge of the importance of handwashing, health care workers wash their hands
      far less often than is indicated. This Issue Brief describes a novel strategy to
      improve handwashing among hospital personnel, by involving the people with the
      most to gain--the patients themselves.

PMID- 12523367
TI  - You're the flight surgeon. Staphylococcal sepsis.

PMID- 12523368
TI  - New acronym needed for congenital infections.

PMID- 12523369
TI  - Current awareness in human psychopharmacology.

PMID- 12523370
TI  - Access to affordable HIV/AIDS drugs: the human rights obligations of
      multinational pharmaceutical corporations.

PMID- 12523371
TI  - Current awareness in human psychopharmacology.

PMID- 12523372
TI  - Effect of bisphosphonate administration on the excretion of stress hormones in
      tail-suspended rats.
AB  - We demonstrated that administration of a bisphosphonate, YH529, prevents the
      development of disuse atrophy of the hind limbs induced by tail-suspension in
      rats. Since tail suspension is accompanied by an increase in the secretion of
      stress hormones, we studied whether administration of bisphosphonate affects the
      secretion of stress hormones during that procedure. Tail suspension was carried
      out in a metabolic cage by connecting a wire inserted through tail bone to the
      ceiling of the cage. The control rat received the same treatment but was not
      suspended. YH529 or a vehicle (PBS=phosphate buffered saline) was administered
      daily starting 3 days before the commencement of tail suspension. Urine samples
      were collected before the wire was inserted (day 0), on the day of insertion (day
      1) and 3, 5 and 7 days after. In the control rats receiving PBS, urinary
      excretion of corticosterone and epinephrine did not change throughout the 7-day
      experimental period. In the control rats receiving YH529, urinary excretion of
      corticosterone increased significantly on the day of tail-piercing and wiring but
      then returned to the prior level. This increase was not observed in the control
      group receiving PBS. In the tail suspended rats, excretion of corticosterone and
      epinephrine increased significantly in both PBS and YH529 groups, the highest
      level being observed on the first day of tail suspension. Although statistically
      not significant, corticosterone excretion on day 1 of tail suspension was higher
      in the YH529 groups than that in the PBS group. It is thus suggested that
      administration of YH529 causes an augmented response to stress load.

PMID- 12523373
TI  - Administration of bisphosphonate prevents disuse bone atrophy induced by tail
      suspension.
AB  - We recently demonstrated that osteopenia induced by rat tail-suspension was
      associated with an initial increase in bone resorption. To study the significance
      of the increase in early bone resorption for osteopenia, we investigated whether
      administration of YH529, a third-generation bisphosphonate, prevents the
      development of osteopenia as evidenced by increased wet weight of the femur,
      together with its calcium and phosphorus contents, when compared with those of
      tail-suspended rats treated with the vehicle alone. These results suggested that
      the initial increase in bone resorption plays an important role in the
      development of osteopenia induced by tail suspension.

PMID- 12523375
TI  - Fractionated-dose effect of X-irradiation on the induction of neural tube defects
      in mice.
AB  - This experiment examined whether mouse embryos have a radio-adaptive response to
      the induction of malformations. Pregnant Slc:ICR mice were exposed to 0.05 Gy X
      radiation followed by 0.5 or 1.0 Gy 4 hr later on day 8 of pregnancy. To compare
      this with the effect of single doses, four other groups were exposed to 0.5,
      0.55, 1.0 or 1.05 Gy. All dams were put to death on day 18, and fetuses were
      examined for malformations. The frequency of neural tube defects induced by the
      fractionated irradiation into 0.05 Gy and 1.0 Gy was significantly higher than
      that induced by single doses of 1.0 and 1.05 Gy. Among groups exposed to a dose
      split into 0.05 and 0.5 Gy, and single doses of 0.5 and 0.55 Gy, there was no
      significant difference in incidence of the malformation. The present findings
      suggest that mouse embryos are not adapted to X-irradiation, but become more
      susceptible following a low-dose exposure.

PMID- 12523374
TI  - Cortical fiber distribution in the somatosensory cortex of rats following
      prenatal exposure to X-irradiation.
AB  - Exposure of fetal rats to X-irradiation at a dose of 1.5 Gy on gestational day 15
      results in severe microcephaly. In these X-irradiated rats with microcephaly, a
      possible alteration of local circuits in the somatosensory cortex was examined
      using a fluorescent dye, DiI. The dye was placed at the superficial part of the
      transversely sectioned somatosensory cortex just beneath the pial surface of both
      the control and X-irradiated rats on postnatal day 11. In the controls, DiI
      labeled fibers showed a layer-dependent distribution in the somatosensory cortex,
      whereas in the X-irradiated rats, this layer-dependent distribution of DiI
      labeled fibers was distorted. Furthermore, the fasciculus observed beneath
      cortical layer VI (white matter), which was made of DiI-labeled axons originating
      from the cortical neurons, was well developed in the controls. On the other hand,
      in the X-irradiated rats, the fasciculus made of DiI-labeled fibers was split,
      reduced in number, and irregularly distributed. These observation suggest that
      prenatal exposure of fetal rats to X-irradiation may affect the development of
      local circuits in the cerebral cortex, and may also damage the axonal projection
      of cortical neurons to the thalamus.

PMID- 12523376
TI  - Modulation of potassium channels by chronic hypoxia in neonatal rat cultured
      ventricular myocytes.
AB  - We studied the effects of long-term exposure to hypoxia on the developmental
      change of transient outward current (Ito) in neonatal rat cultured ventricular
      myocytes. Ventricular myocytes of day-old neonatal rat hearts were cultured in
      normoxic condition (21%, O2) for 15 days. Some cells were cultured at lower O2
      concentration of 7.5% from day 6 to day 15. During 6-15 days of cultivation in
      normoxic condition, a two to three fold increase (n=11-12) in Ito density was
      observed without changes in the kinetics of current inactivation. In the hypoxic
      condition during the same culture period, the developmental increment in Ito was
      reduced to 53% (n=8) and was characterized by slow kinetics of the inactivation
      process. These results suggest that the development of Ito is influenced by the
      oxygen concentration, and that the remarkable increase in Ito after birth may
      result from an elevation in blood oxygen concentration during the perinatal
      period.

PMID- 12523377
TI  - Calcium metabolism under stress and in repose.
AB  - Derangement of calcium metabolism, although perhaps not as dramatic as that of
      the cardiovascular or vestibular systems, constitutes one of the major threats to
      the health of participants in exploration of space. On the basis of studies in
      immobilized subjects, the clinical disorders most likely to be encountered during
      prolonged space flight are primarily the consequence of an imbalance between bone
      formation and resorption (favoring the latter): (1) loss of skeletal mass,
      leading to osteoporosis; (ii) hypercalcemia; and (iii) hyper-calciuria, with the
      attendant risk of nephrolithiasis. By itself, loss of skeletal mass would not be
      expected to pose an in-flight hazard, but hypercalcemia or nephrolithiasis could
      jeopardize lives or mission success. Such data as are available from in-flight
      studies tend to support the use of immobilization as a terrestrial model for
      alterations in calcium metabolism during space flight. A variety of prophylactic
      measures have been attempted with this model in an effort to modify the observed
      disorders. Although there is some evidence that hypercalcemia and hypercalciuria
      can be reduced or prevented, negative calcium balance has not been completely
      reversed. Perhaps the most successful prophylactic measure utilized to date has
      been dietary supplementation of both calcium and inorganic phosphate. With the
      wide variety of excellent study tools which are currently available for
      application to this field, significantly increased efforts are clearly required
      both to define the basic mechanism of immobilization-induced skeletal losses and
      to devise new prophylactic or therapeutic approaches.

PMID- 12523378
TI  - Energy requirements of man living in a weightless environment.
AB  - The ability to maintain energy balance is a vital factor in maintaining body
      composition. A negative energy balance requires that body tissue be consumed to
      sustain biochemical and physiological activity. Such a caloric imbalance coupled
      with reduced physical activity results in (among other things): a negative
      balance which can not be reversed by increased protein intake; negative balances
      for electrolytes; and a suspension of erythrocyte production. Body weight losses
      were experienced by all astronauts during Gemini and Apollo missions. Data on the
      magnitude of the changes, together with data on energy consumption, were used to
      calculate energy imbalances. These data, when compared with results obtained from
      precise energy balance measurements made on 64 men living in low pressure
      chambers, show close correlation. When energy requirements are expressed in
      kilocalories per kilogram of body weight, the difference in energy requirements
      among the astronauts and chamber subjects was small and not statistically
      significant. These data indicated that reliable prediction of energy needs for
      astronauts, during long-term space missions, can be made by studying either the
      astronauts or healthy subjects in a ground-based environment similar to that of
      the spacecraft. These data also indicate that changes in body weight and certain
      other body measurements detected during Gemini and Apollo missions were probably
      caused, at least in part, by a calorie deficit.

PMID- 12523379
TI  - Survival of bacterial isolates exposed to simulated Jovian trapped radiation belt
      electrons and solar wind protons.
AB  - With missions to Jupiter, the spacecraft will be exposed for extended durations
      to solar wind radiation and the Jovian trapped radiation belt. This study is
      designed to determine the effect of these radiation environments on spacecraft
      bacterial isolates. The information can be used in the probability of
      contamination analysis for these missions. A bacterial subpopulation from Mariner
      Mars 1971 spacecraft (nine spore-forming and three non-spore-forming isolates)
      plus two comparative organisms, Staphylococcus epidermidis ATCC 17917 and a
      strain of Bacillus subtilis var. niger, were exposed to 2, 12, and 25 MeV
      electrons at different doses with simultaneous exposure to a vacuum of 1.3 x 10(
      4) N m-2 at 20 and -20 degrees C. The radioresistance of the subpopulation was
      dependent on the isolate, dose and energy of electrons. Temperature affected the
      radioresistance of only the spore-forming isolates. Survival data indicated that
      spores were reduced approximately 1 log/1500 J kg-1 (10 J kg-1=1 krad), while non
      spore-forming isolates (micrococci) were reduced 1.5-2 logs/1500 J kg-1 with the
      exception of an apparent radioresistant isolate whose resistance approached that
      of the spores. The subpopulation was found to be less resistant to lower energy
      than to higher energy electrons. The bacterial isolates were exposed to 3 keV
      protons under the same conditions as the electrons with a total fluence of 1.5 x
      10(13) p cm-2 and a dose rate of 8.6 x 10(9) p cm-2 s-1. The results showed that
      only 20% of S. epidermidis and 45% of B. subtilis populations survived exposure
      to the 3 keV protons, while the mean survival of the spacecraft subpopulation was
      45% with a range from 31.8% (non-spore-former) to 64.8% (non-spore-former). No
      significant difference existed between spore-forming and non-spore-forming
      isolates.

PMID- 12523380
TI  - On the mechanism of adaptation of micro-organisms to conditions of extreme low
      humidity.
AB  - Low humidity is considered one of the main obstacles for life on Mars. Mechanisms
      of adaptation to extreme low humidity are investigated in asporogenic yeasts.
      Cryptococcus albidus var. diffluens inhabits the high mountain deserts of the
      Pamirs and the Tien Shan. The spin-echo nuclear magnetic resonance method shows
      that different ways of drying do not extract all liquid water from the cells.
      Residual humidity of the Cryptococcus cells may reach 30%. The polysaccharide
      capsule of Cryptococcus delays the drying process noticeably and also collects
      moisture at low relative humidity. The considerable quantity of conserved liquid
      water allows Cryptococcus to adapt to the great periodic oscillations of relative
      humidity resulting from the great diurnal temperature changes in the high
      mountain deserts. Data obtained indicate the presence of a humidity regulating
      mechanism on the cellular level in lower plants.

PMID- 12523381
TI  - On the multiplication of xerophilic micro-organisms under simulated Martian
      conditions.
AB  - The environmental conditions prevailing on Mars would supposedly favour the
      existence there of micro-organisms belonging to xerophiles, anaerobes, or micro
      aerophiles, oligonitrophiles, which are able to grow in wide temperature
      intervals. From soil samples taken in deserts and tundra, antarctic halophilic
      bacteria, able to grow in liquid media containing 20-25% of sodium chloride, were
      isolated. Some of these cultures appeared to be also osmophilic (growth on media
      with 50% glucose); they grew at temperatures from 5 degrees C to 50 degrees C,
      and developed on media without a nitrogen source (oligonitrophiles). Of special
      interest was the halophilic and osmophilic form of Bacillus megaterium isolated
      from the Nubian desert. In experiments with this bacterium the following
      technique was used. A thin film of potato extract agar was prepared on a glass
      slide and dried over a saturated K2SO4 solution in a closed container up to the
      level of maximal hygroscopic moisture. The cell suspension was then sprayed on to
      the agar surface, the film dried again at 45 degrees C, and the glass slide put
      in the test tube over the saturated solution of K2SO4. The test tube was
      evacuated, flushed three times with a gas mixture containing 80% CO2 plus 20% Ar,
      and sealed. Under these conditions the water content of the agar film was equal
      to the maximal hygroscopic moisture; only the xerophilic form of bacteria are
      able to develop at this moisture level. This halophilic strain of Bac. megaterium
      grew satisfactorily under these conditions, as did a halophilic and osmophilic
      strain of Mycococcus ruber isolated in Antarctica. Both the halophilic strain of
      Bac. megaterium and that of M. ruber were able to grow under simulated Martian
      conditions. Xerophily and halophily may be linked. This assumption was supported
      by relatively high incidence of xerophilic forms among halophilic bacteria
      isolated from different soils of both high and low salt content as well as from
      salty muds.

PMID- 12523382
TI  - Biomechanics of locomotion in subgravity.
AB  - The speed of walking or running on the moon as compared with earth is appreciably
      reduced, in spite of mechanisms of compensation taking place such a forward
      leaning of the body and an increase of the horizontal component of the push of
      the foot on the ground. However on the moon the same speed of locomotion as on
      earth can be reached by shifting to a different mechanism of locomotion, i. e.
      progression by jumps, which becomes possible on the moon because of the reduction
      of the body weight. The energy cost of locomotion is certainly less on the moon
      than on earth, about 1/6. Were the subject not restrained by the space suit,
      progression by jumps at 20 km hr-1 on the moon would cost no more than 10 ml kg-1
      min-1 of oxygen, the same as walking on earth at 6 km hr-1. Maximal acceleration
      of the body as in sprinting, or deceleration as in stopping, attains much higher
      values on earth than on the moon. While sprinting on earth may involve the
      maximal muscular power, sprinting or progressing at the highest speed on the moon
      involves only a fraction of the maximal power, mainly because of the reduced
      maximal frequency of the steps (or jumps). The maximal height of the jump on both
      feet on the moon could attain 4 m in the unrestricted subject. An analysis is
      wanted on the restriction of the movements brought about by the space suit and on
      the energy cost of progression.

PMID- 12523383
TI  - Solid state AgCl detectors for nuclear tracks with on- and off-response at
      choice: applications to life sciences.
AB  - A new concept of trackforming solid state detectors is presented. These detectors
      record and accumulate tracks of ionizing particles which can be revealed if they
      are irradiated with yellow light during the passage of the particle through the
      detector; otherwise the tracks are dropped by fading. Tracks stabilized by yellow
      light are stable for months. The detectors consist of thin layers of 200-300
      micrometers of Cd-doped AgCl crystals, supported by a thin plate of quartz glass.
      The invisible latent tracks in these detectors are revealed at microscopically
      visible size by ultraviolet light. The sensitivity of the crystals against
      particles of different specific energy transfer depends upon the concentration of
      Cd; these have rather good thresholds, which permit selective recording in a well
      known manner. These AgCl(Cd) crystals have a unique property amongst trackforming
      detectors; their response can be switched on and off at choice, for instance by
      electronic triggering of the stabilizing accompanying yellow light. This allows a
      time assignment of particle tracks, or restriction to tracks of desired
      particles. Examples of tracks and of applications in cosmic ray research, heavy
      ion physics, radiobiology and dosimetry are given.

PMID- 12523384
TI  - Estimation of the biological danger of the very high energy component of space
      radiation.
AB  - In modelling the action of the high energy component of space radiation in a
      space ship, the secondary radiation resulting from the interaction of 76 GeV
      protons with a target was used. The radiation flow consisted of neutrons, mesons
      of different kinds and charges, protons and gamma-quanta of wide energy spectrum.
      We studied the influence of radiation on the survival of E. coli B and T4Br+
      bacteriophage, on the growth, dry weight and survival of Vicia faba, on the
      frequency of chromosome aberrations, and number of cells with abnormal mitoses,
      on the rate of post-irradiation recovery according to these characteristics, and
      also on the yield of the r-mutants of T4Br+ bacteriophage, their distribution and
      biochemical identification. The probability of strong interactions with intra
      nuclear cascade processes was minor. Their action on the background of the main
      mass of radiation with an RBE of less than 1 could be considerably masked.
      Nevertheless, the RBE of combined secondary radiation was sufficiently greater
      than 137Cs radiation; from approximate curves, it was from 1.2 to 4.0 times as
      great and in single experimental points it was more than 5. The spectrum of
      mutation was also different.

PMID- 12523385
TI  - Effects of heavy ions on bacteria.
AB  - Genetically well-known bacteria have been used to study efficiencies of heavy
      ions for mutation induction. For space experiments a technique of correlation of
      tracks of particles (in emulsion stacked on and between Petri dishes) with
      individual mutations, has been designed and checked in balloon flights. No clear
      cut results could be obtained without previous identification of genetic markers
      sensitive to irradiation by heavy ions. Accelerator experiments were performed at
      the Berkeley HILAC for systematic study. The results obtained on a strain of E.
      coli K12F- requiring threonine, leucine and arginine showed that the cell
      inactivation kinetics for gamma rays, helium, carbon and oxygen ions were almost
      identical (LD90 approaches 22krads) while argon was less effective (LD90
      approaches 40 krads). Heavy ions up to oxygen were either equally or less
      efficient than gamma rays for induction of reverse mutations. Discrepancies
      between these findings and previous data on bacteria, yeast and Neurospora
      systems are discussed on the basis of radiosensitivity, ploidy, deletions,
      forward and reverse mutations.

PMID- 12523386
TI  - Institution residents continue to decrease as community setting residents grow at
      an accelerating pace.

PMID- 12523387
TI  - Amino acid production processes.
AB  - With the exploitation of new uses and the growing markets of amino acids, amino
      acid production technology has made large progress during the latter half of the
      20th century. Fermentation technology has played crucial roles in this progress,
      and currently the fermented amino acids represent chief products of biotechnology
      in both volume and value. This area is highly competitive in the world market and
      process economics are of primary importance. For cost-effective production, many
      technologies have been developed to establish high-productive fermentation and
      recovery processes. The producer organisms used in large-scale, well-established
      processes have been developed to a high level of production efficiency. The tools
      of genetic engineering of amino acid-producing organisms have been well developed
      and are now being applied for enlargement of biosynthetic and transport capacity,
      which is beginning to have a great impact on the amino acid industry.
      Furthermore, the rapid strides in genome analysis are bound to revolutionize the
      strain improvement methodology.

PMID- 12523388
TI  - Metabolic engineering of glutamate production.
AB  - Since the discovery of Corynebacterium glutamicum as an efficient glutamate
      overproducing microorganism in 1957, the production of L-amino acids by the
      fermentative method has become one of the most important research-target of
      industrial microbiology. Several research groups have developed metabolic
      engineering principles for L-amino acid-producing C. glutamicum strains over the
      last four decades. The mechanism of L-glutamate-overproduction by the
      microorganism is very unique and interesting. L-Glutamate overproduction by this
      bacterium, a biotin auxotroph, is induced by a biotin limitation and suppressed
      by an excess of biotin. Addition of a surfactant or penicillin is known to induce
      L-glutamate overproduction under excess biotin. After the development of the
      general molecular biology tools such as cloning vectors and DNA transfer
      technique, genes encoding biosynthetic enzymes were isolated. With those genes
      and tools, recombinant DNA technology can be applied in analysis of biosynthetic
      pathways and strain construction of C. glutamicum. In this review, key points of
      the L-glutamate biosynthetic pathways are summarized and the recent studies about
      triggering mechanism of L-glutamate overproduction by C. glutamicum are
      introduced. Then the metabolic flux analysis of L-glutamate overproduction is
      explored.

PMID- 12523389
TI  - Biotechnological manufacture of lysine.
AB  - L-Lysine has been manufactured using Corynebacterium glutamicum for more than 40
      years. Nowadays production exceeds 600,000 tons per year. Based on conventionally
      bred strains, further improvement of lysine productivity has been achieved by
      genetic engineering. Pyruvate carboxylase, aspartate kinase, dihydrodipicolinate
      synthase, homoserine dehydrogenase and the specific lysine exporter were shown to
      be key enzymes for lysine production and were characterized in detail. Their
      combined engineering led to a striking increase in lysine formation. Pathway
      modeling with data emerging from 13C-isotope experiments revealed a coordinated
      flux through pentose phosphate cycle and tricarboxylic acid cycle and intensive
      futile cycling between C3 compounds of glycolysis and C4 compounds of
      tricarboxylic acid cycle. Process economics have been optimized by developing
      repeated fed-batch techniques and technical continuous fermentations. In
      addition, on-line metabolic pathway analysis or flow cytometry may help to
      improve the fermentation performance. Finally, the availability of the
      Corynebacterium glutamicum genome sequence has a major impact on the improvement
      of the biotechnological manufacture of lysine. In this context, all genes of the
      carbon flow from sugar uptake to lysine secretion have been identified and are
      accessible to manipulation. The whole sequence information gives access to post
      genome technologies such as transcriptome analysis, investigation of the proteome
      and the active metabolic network. These multi-parallel working technologies will
      accelerate the generation of knowledge. For the first time there is a chance of
      understanding the overall picture of the physiological state of lysine
      overproduction in a technical environment.

PMID- 12523390
TI  - The threonine story.
AB  - L-Threonine is an essential amino acid which has recently been brought into
      agricultural industry for balancing the livestock feed. L-Threonine is produced
      by microbial synthesis using glucose or sucrose as substrates. For the process to
      be cost-effective, the microbial strain must be capable of threonine
      overproduction. This paper reviews the biochemical pathways of L-threonine
      synthesis in bacteria and the regulation of these pathways, the principles and
      the techniques of constructing high-producing strains, and the most efficient
      strains thus developed.

PMID- 12523391
TI  - Economic aspects of amino acids production.
AB  - Amino acids represent basic elements of proteins, which as a main source of
      nutrition themselves serve as a major reserve for maintaining essential functions
      of humans as well as animals. Taking the recent state of scientific knowledge
      into account, the industrial sector of amino acids is a priori "suitable" to a
      specific kind of an ecologically sound way of production, which is based on
      biotechnology. The following article may point out characteristics of this
      particular industrial sector and illustrates the applicability of the latest
      economic methods, founded on development of the discipline of bionics in order to
      describe economic aspects of amino acids markets. The several biochemical and
      technological fields of application of amino acids lead to specific market
      structures in high developed and permanently evolving systems. The Harvard
      tradition of industrial economics explains how market structures mould the
      behaviour of the participants and influences market results beyond that. A global
      increase in intensity of competition confirms the notion that the supply-side is
      characterised by asymmetric information in contrast to Kantzenbachs concept of
      "narrow oligopoly" with symmetrical shared knowledge about market information.
      Departing from this point, certain strategies of companies in this market form
      shall be derived. The importance of Research and Development increases rapidly
      and leads to innovative manufacturing methods which replace more polluting
      manufacturing processes like acid hydrolysis. In addition to these modifications
      within the production processes the article deals furthermore with the pricing
      based on product life cycle concept and introduces specific applications of tools
      like activity based costing and target costing to the field of amino acid
      production. The authors come to the conclusion that based on a good
      transferability of latest findings in bionics and ecological compatibility
      competitors in amino acids manufacturing are well advised to exercise concepts of
      the management of complex systems in order to choose the right strategy towards
      gaining market leadership.

PMID- 12523392
TI  - Wisconsin pulls out ahead on mercury controls.

PMID- 12523393
TI  - UNEP takes first steps to control worldwide mercury releases. United Nations
      Environmental Programme.

PMID- 12523394
TI  - Little law could block major government decisions.

PMID- 12523395
TI  - More evidence that atrazine may affect frog sexuality.

PMID- 12523396
TI  - Spilled oil persists after 30 years.

PMID- 12523397
TI  - Great Lakes' cleanup too little, too late.

PMID- 12523398
TI  - Salty incinerator fly ash affects soil microbes' activity.

PMID- 12523400
TI  - Solar power competition.

PMID- 12523399
TI  - Farmers unprepared for methyl bromide ban.

PMID- 12523401
TI  - Microbes and fungi help clean the air.

PMID- 12523402
TI  - Contaminant amplification in the environment.

PMID- 12523403
TI  - In situ treatment of chromium-contaminated groundwater.

PMID- 12523404
TI  - Uraninite and fullerene in atmospheric particulates.
AB  - Particulates emitted from coal-burning power plants typically contain very small
      amounts of uranium (<10 ppm). Because of the extremely low concentrations, the
      form of the uranium has been unknown. Using a variety of advanced electron
      microscopy techniques, we have identified for the first time nanocrystals of
      uraninite, UO2+x, encapsulated in carbonaceous matter (< or = 50 nm) similar to
      fullerene. We have also identified, for the first time, closely associated
      fullerenes, C60. The "carbon-caged" nanocrystals of uraninite are protected from
      the immediate oxidation that would lead to increased mobility of uranium in the
      environment. Still, the presence of uranium in the very fine fraction of
      atmospheric particulates provides another pathway for radiation exposure.

PMID- 12523405
TI  - Quantitative time-resolved monitoring of nitrate formation in sea salt particles
      using a CCSEM/EDX single particle analysis.
AB  - Progress of the nitrate formation in individual sea salt particles was detected
      as a function of time using aerosol samples collected during the TexAQS 2080
      experiment We demonstrate that the time-resolved collection approach coupled with
      the automated EDX single particle analysis made it possible to follow in detail
      the time evolution of sea salt particles within a diverse aerosol mixture. Using
      a custom built Time-Resolved Aerosol Collector (TRAC), particulate samples were
      taken sequentially on grid-supported 50 nm carbon films with a time resolution of
      10 min between two consecutive samples. The samples were analyzed in the
      laboratory using Computer Controlled Scanning Electron Microscopy with Energy
      Dispersed analysis of X-rays (CCSEM/EDX). Between midnight of 08/16/00 and the
      early morning of 08/17/00, a steady, particularly sea salt rich aerosol was
      observed at the measurement site, which later showed the effects of atmospheric
      processing. During the night of 08/17/00 the sea salt particles were almost
      unprocessed, having elemental composition close to that of seawater. By 12 noon,
      the evolving atmosphere was able to completely convert them, predominantly to
      sodium nitrate particles. During the next night this process had nearly stopped
      and fairly virgin sea salt particles appeared again.

PMID- 12523406
TI  - Airborne respirable silica near a sand and gravel facility in central California:
      XRD and elemental analysis to distinguish source and background quartz.
AB  - Despite the potential toxicity of respirable quartz to humans, little is known
      about the transport of airborne quartz from sources to receptors and how to
      distinguish anthropogenically generated quartz from natural background in a
      receptor sample. Airborne quartz emissions near a sand and gravel facility were
      determined using PM10 and PM2.5 filter samples collected at four downwind sites
      (D1: 22 m, D2: 62 m, D3: 259 m, and D4: 745 m from the facility) as well as one
      upwind site (U1: 1495 m) during summer sampling. X-ray diffraction was used to
      determine quartz concentration and elemental composition was analyzed using PIXE,
      XRF, PESA, and HIPS techniques. Elemental composition of the PM samples was used
      to determine the X-ray mass absorption coefficients that are essential for
      accurate quartz quantification by XRD. Elemental composition was found to be a
      useful tool to distinguish source and background crystalline silica. Both PM10
      and PM2.5 samples collected at the D1, D2, and D3 sites contained more Si, Al,
      and Fe and less H, Na, and S, compared to those at the U1 site, whereas site D4
      sample compositions were similar to those at the U1 site. A composite variable,
      SOIL/(H+Na+S), where SOIL = 2.20Al + 2.49Si + 1.63Ca + 1.94Ti + 2.42Fe, was used
      to distinguish source materials from background. Average dry season quartz
      concentrations in replicate PM10 samples were 4.6 +/- 0.9) microg m(-3) at U1,
      60.6 (+/- 5.4) microg m(3) at D1, 62.4 (+/- 3.6) at D2, 32.6 (+/- 2.1) microg m(
      3) at D3, and 9.41 (+/- 0.9) microg m(-3) at D4. The mass fraction of quartz was
      the highest at the D1 site and decreased with increasing distance from the
      facility. The mass of PM2.5 samples was too low to determine quartz
      concentrations. These results identify the facility as the main source of quartz
      and other silicate minerals downwind of the plant and that the air quality of the
      most remote sampling site, located approximately 750 m downwind, was still
      impacted by the facility's activity.

PMID- 12523407
TI  - Anthropogenic sources of arsenic and copper to sediments in a suburban lake,
      Northern Virginia.
AB  - Mass balances of total arsenic and copper for a suburban lake in densely
      populated northern Virginia were calculated using date collected during 1998.
      Mass-balance terms were precipitation; stream inflow, including road runoff;
      stream outflow; and contributions from leaching of pressure-treated lumber. More
      mass of arsenic and copper was input to the lake than was output the 1998 lake
      retention rates were 70% for arsenic and 20% for copper. The arsenic mass balance
      compared well with a calculated annual mass accumulation in the top 1 cm of the
      lake sediments; however, the calculated contribution of copper to the lake was
      insufficient to account for the amount of copper in this zone. Leaching
      experiments were conducted on lumber treated with chromated copper arsenate (CCA)
      to quantify approximate amounts of arsenic and copper contributed by this source.
      Sources to lake sediments included leaching of CCA-treated lumber (arsenic, 50%;
      copper, 4%), streamwater (arsenic, 50%; copper, 90%), and atmospheric deposition
      (arsenic, 1%; copper, 3%). Results of this study suggest that CCA-treated lumber
      and road runoff could be significant nonpoint sources of arsenic and copper,
      respectively, in suburban catchments.

PMID- 12523408
TI  - Soot-carbon influenced distribution of PCDD/Fs in the marine environment of the
      Grenlandsfjords, Norway.
AB  - The particle associations of polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDD/Fs) were studied in both the water column and
      the surface sediments of a marine fiord system and were found to poorly obey
      expectations from the organic matter partitioning (OMP) paradigm. The field
      observations were instead consistent with the presence of a stronger sorbent
      subdomain such as pyrogenic soot-carbon (SC) playing an important role in
      affecting the environmental distribution and fate of PCDD/Fs. Solid-water
      distribution coefficients (Kd) of PCDD/ Fs actually observed in the water column
      were several orders of magnitude above predictions from a commonly used OMP
      model. Even when these elevated Kd values were normalized to the particulate
      organic carbon (POC) content (i.e., K(OC)), the variability in K(OC) for
      individual PCDD/ Fs at different fjord locations and seasons of factors 100-1,000
      suggested that bulk organic matter was not the governing sorbent domain of the
      suspended particles. Further, POC-normalized particle concentrations of PCDD/ Fs
      (C(OC)) in a vertical profile (surface water-bottom water-surface sediment)
      revealed a strong increasing trend with depth. Factors of about 100 higher Coc
      for all PCDD/Fs in the sediment than in the surface water could not be explained
      by higher fugacity in the surrounding deep water nor with C:N or delta13C indexes
      of selective aging of the bulk organic matter. Instead this was hypothesized to
      reflect selective preservation of a more recalcitrant and highly sorbing, but
      minor, subdomain such as soot. The extent of enhanced PCDD/F sorption, above the
      OMP predictions, was positively correlated with the SC:POC ratio of the suspended
      particles in surface and deep waters. Finally, the geographical distribution of
      sedimentary PCDD/F concentrations were better explained by the SC content than by
      the bulk OC content of the sediment. Altogether, these field-based findings add
      to recent laboratory-based sorption studies to suggest that we need to consider
      both amorphous OC partitioning domains and SC particles as carriers of planar
      aromatic contaminants if we are to explain the environmental distribution and
      fate of pollutants such as PCDD/Fs.

PMID- 12523409
TI  - In situ measurement of polychlorinated biphenyls in the waters of San Diego Bay,
      California.
AB  - Sediments of San Diego Bay (SDB) are known to contain elevated levels of
      polychlorinated biphenyls (PCBs). While numerous efforts have been made to
      monitor the spatial or temporal trends of contamination in SDB, no studies have
      been directed toward measurements of water column contamination. We measured PCB
      concentrations in the water column of SDB with an in situ sampling system. Except
      for one sample collected near the bay mouth, all other samples contained higher
      PCB concentrations than the 30-day average discharge limit established by the
      California Ocean Plan. The highest concentrations of water column PCBs occurred
      in the Central Bay, consistent with the previous findings that sediments in the
      Central Bay contained higher PCB levels than those in the North and South Bays.
      Based on the water volume of 2.2 x 10(8) cm3 at a lower water level, it was
      estimated that approximately 1,000 g of PCBs is transported out of SDB via tidal
      exchange annually. This indicates that water column transport driven by tidal
      exchange is a viable mechanism reducing PCB contamination within SDB.

PMID- 12523410
TI  - Aircraft measurements of nitrogen and phosphorus in and around the Lake Tahoe
      Basin: implications for possible sources of atmospheric pollutants to Lake Tahoe.
AB  - Atmospheric deposition of nitrogen (N) and phosphorus (P) into Lake Tahoe appears
      to have been a major factor responsible for the shifting of the lake's nutrient
      response from N-limited to P-limited. To characterize atmospheric N and P in and
      around the Lake Tahoe Basin during summer, samples were collected using an
      instrumented aircraft flown over three locations: the Sierra Nevada foothills
      east of Sacramento ("low-Sierra"), further east and higher in the Sierra ("mid
      Sierra"), and in the Tahoe Basin. Measurements were also made within the smoke
      plume downwind of an intense forest fire just outside the Tahoe Basin. Samples
      were collected using a denuder-filter pack sampling system (DFP) and analyzed for
      gaseous and water-soluble particle components including HNO3/ NO3-, NH3 /NH4+,
      organic N (ON), total N, SRP (soluble reactive phosphate) and total P. The
      average total gaseous and particulate N concentrations (+/- 1sigma) measured over
      the low- and mid-Sierra were 660 (+/- 270) and 630 (+/- 350) nmol N/m3-air,
      respectively. Total airborne N concentrations in the Tahoe samples were one-half
      to one-fifth of these values. The forest fire plume had the highest concentration
      of atmospheric N (860 nmol N/m3-air) and a greater contribution of organic N (ON)
      to the total N compared to nonsmoky conditions. Airborne P was rarely observed
      over the low- and mid-Sierra but was present at low concentrations over Lake
      Tahoe, with average +/- 1sigma) concentrations of 2.3 +/- 2.9 and 2.8 +/- 0.8
      nmol P/m3-air under typical clear air and slightly smoky air conditions,
      respectively. Phosphorus in the forestfire plume was present at concentrations
      approximately 10 times greater than over the Tahoe Basin. P in these samples
      included both fine and coarse particulate phosphate as well as unidentified,
      possibly organic, gaseous P species. Overall, our results suggest that out-of
      basin emissions could be significant sources of nitrogen to Lake Tahoe during the
      summer and that forest fires could be important sources of both N and P.

PMID- 12523411
TI  - Accumulation of COGEMA-La Hague-derived reprocessing wastes in French salt marsh
      sediments.
AB  - Over the past five decades, authorized low-level discharges from coastal nuclear
      facilities have released significant quantities of artificial radionuclides into
      the marine environment. In northwest Europe, the majority of the total discharge
      has derived from nuclear reprocessing activities at Sellafield in the United
      Kingdom and COGEMA-La Hague in France. At the Sellafield site, a significant
      amount of the discharges has been trapped in offshore fine sediment deposits, and
      notably in local coastal and estuarine sediments, and much research has been
      focused on understanding the distribution, accumulation, and reworking of long
      lived radionuclides in these deposits. In contrast, there are few high-resolution
      published data on the vertical distribution of radionuclides in fine-grained
      estuarine sediments near, and downstream of, COGEMA-La Hague. This paper
      therefore examines the vertical distribution of a range of anthropogenic
      radionuclides in dated salt marsh cores from two estuaries, one adjacent to, and
      the other downstream of, the COGEMA-La Hague discharge point (the Havre de
      Carteret at Barneville-Carteret and the Baie de Somme, respectively). The
      radionuclides examined show a vertical distribution which predominantly reflects
      variations in input from COGEMA-La Hague (albeit much more clearly at Barneville
      Carteret than at the Baie de Somme site), and Pu isotopic ratios are consistent
      with a La Hague, rather than weapons' fallout, source. Because of sediment
      mixing, the marshes apparently retain an integrated record of the La Hague
      discharges, rather than an exact reproduction of the discharge history. Sorption
      of radionuclides increases in the order 90Sr < 137Cs < 60Co < 239,240Pu, which is
      consistent with Kd values reported in the literature. In general, the
      radionuclide activities observed at the sites studied are low (particularly in
      comparison with salt marsh sediments near the Sellafield facility), but are
      similar to those found in areas of fine sedimentation in the central Channel.
      These marshes are not major sinks for discharged reprocessing wastes.

PMID- 12523412
TI  - Triclosan: occurrence and fate of a widely used biocide in the aquatic
      environment: field measurements in wastewater treatment plants, surface waters,
      and lake sediments.
AB  - Triclosan is used as an antimicrobial agent in a wide range of medical and
      consumer care products. To investigate the occurrence and fate of triclosan in
      the aquatic environment, analytical methods for the quantification of triclosan
      in surface water and wastewater, sludge, and sediment were developed.
      Furthermore, the fate of triclosan in a wastewater treatment plant (biological
      degradation, 79%; sorption to sludge, 15%; input into the receiving surface
      water, 6%) was measured during a field study. Despite the high overall removal
      rate, the concentration in the wastewater effluents were in the range of 42-213
      ng/L leading to concentrations of 11-98 ng/L in the receiving rivers. Moreover, a
      high removal rate of 0.03 d(-1) for triclosan in the epilimnion of the lake
      Greifensee was observed. This is due to photochemical degradation. The measured
      vertical concentration profile of triclosan in a lake sediment core of lake
      Greifensee reflects its increased use over 30 years. As the measured
      concentrations in surface waters are in the range of the predicted no effect
      concentration of 50 ng/L, more measurements and a detailed investigation of the
      degradation processes are needed.

PMID- 12523413
TI  - Polychlorinated naphthalene levels, distribution, and biomagnification in a
      benthic food chain in the Baltic Sea.
AB  - The scientific literature contains little information regarding bioaccumulation
      and biomagnification of polychlorinated naphthalenes (PCNs) in food webs. Here we
      present new information on the food chain transfer of PCNs within a food chain in
      a subarctic environment PCNs (tetra- to hepta-chloro congeners) were measured in
      surface sediments and in a marine benthic food chain, comprising amphipods,
      isopods, and fourhorned sculpins. Samples were collected from five locations in
      the Gulf of Bothnia, northern Baltic Sea. PCN concentrations in the sediments
      were similar to background levels determined previously in sediments from the
      northern hemisphere. Measurement of the carbon content of the sediments allowed
      the calculation of biota to sediment accumulation factors (BSAFs). Tetra- and
      penta-CNs exhibited BSAF values greater than one, while BSAFs for the more
      chlorinated PCNs were less than one. This suggests more efficient assimilation,
      by amphipods, of the less chlorinated PCNs. A decrease in sigmaPCN concentrations
      from the lowest to the highest trophic level was demonstrated (amphipods: 10-69
      ng/g lw, isopods: 3.9-16 ng/g lw; fourhorned sculpins: 0.54-1.5 ng/g lw).
      Biomagnification factors (BMFs) were calculated based on the concentrations of
      the congeners. These indicated that a few congeners biomagnified significantly:
      the highest BMFs (0.09-1.4) were found for 2,3,6,7-substituted congeners and
      those lacking adjacent hydrogen-substituted carbon atoms.

PMID- 12523414
TI  - Investigation of the volatile organic substances that cause the characteristic
      odor of pentachlorophenol treated wood utility poles.
AB  - The nature of the volatile organic compounds that could be at the origin of the
      characteristic odor of treated wood utility poles was investigated by the study
      of compositional changes in the chromatographic profiles of fresh
      pentachlorophenol (PCP) solvent samples and weathered samples collected from an
      in-service red pine pole. Over 99 peaks were identified in the chromatogram of
      the fresh solvent from which a large portion of the C3-, C4-, C5-, C6
      alkylbenzene isomers and early eluting n-alkanes was missing from the analysis of
      weathered samples. Three domains in the chromatographic profile (volatile,
      semivolatile, and nonvolatile components) were confirmed by assessing the
      headspace of fresh-PCP solvent samples using direct syringe sampling and solid
      phase microextraction. A first level of field validation was achieved using an
      emission cell for measuring substances emanating from sapwood specimens at
      different temperatures. The average latent heat of vaporization (deltaHvap) of
      the PCP-solvent components was estimated at 99.9 kJ/mol from these results.
      Finally, the analysis of airborne substances at a treating plant and a utility
      pole storage site confirmed that the C4-, C5-, and C6-alkylbenzene isomers could
      contribute to the characteristic odor perceived by humans.

PMID- 12523415
TI  - Combining selective sequential extractions, X-ray absorption spectroscopy, and
      principal component analysis for quantitative zinc speciation in soil.
AB  - Selective sequential extractions (SSE) and, more recently, X-ray absorption fine
      structure IXAFS) spectroscopy have been used to characterize the speciation of
      metal contaminants in soils and sediments. However, both methods have specific
      limitations when multiple metal species coexist in soils and sediments. In this
      study, we tested a combined approach, in which XAFS spectra were collected after
      each of 6 SSE steps, and then analyzed by multishell fitting, principal component
      analysis (PCA) and linear combination fits (LCF), to determine the Zn speciation
      in a smelter-contaminated, strongly acidic soil. In the topsoil, Zn was
      predominately found in the smelter-emitted minerals franklinite (60%) and
      sphalerite (30%) and as aqueous or outer-sphere Zn2+ (10%). In the subsoil,
      aqueous or outer-sphere Zn2+ prevailed (55%), but 45% of Zn was incorporated by
      hydroxy-Al interlayers of phyllosilicates. Formation of such Zn-bearing hydroxy
      interlayers, which has been observed here for the first time, may be an important
      mechanism to reduce the solubility of Zn in those soils, which are too acidic to
      retain Zn by formation of inner-sphere sorption complexes, layered double
      hydroxides or phyllosilicates. The stepwise removal of Zn fractions by SSE
      significantly improved the identification of species by XAFS and PCA and their
      subsequent quantification by LCF. While SSE alone provided excellent estimates of
      the amount of mobile Zn species, it failed to identify and quantify Zn associated
      with mineral phases because of nonspecific dissolution and the precipitation of
      Zn oxalate. The systematic combination of chemical extraction, spectroscopy, and
      advanced statistical analysis allowed us to identify and quantify both mobile and
      recalcitrant species with high reliability and precision.

PMID- 12523416
TI  - Field estimate of net trophic transfer efficiency of PCBs to Lake Michigan
      chinook salmon from their prey.
AB  - Chinook salmon (Oncorhynchus tshawytscha) has been the predominant piscivore in
      Lakes Michigan, Huron, and Ontario since the 1970s, and therefore accurate
      quantification of its energy budget is needed for effective management of Great
      Lakes fisheries. A new approach of evaluating a fish bioenergetics model in the
      field involves field estimation of the efficiency with which the fish retains
      PCBs from its food. We used diet information, PCB determinations in both chinook
      salmon and their prey, and bioenergetics modeling to generate a field estimate of
      the efficiency with which Lake Michigan chinook salmon retain PCBs from their
      food. Our field estimate is the most reliable field estimate to date because (a)
      the estimate was based on a relatively high number (N = 142) of PCB
      determinations for chinook salmon from Wisconsin waters of Lake Michigan in 1985,
      (b) a relatively long time series (1978-1988) of detailed observations on chinook
      salmon diet in Lake Michigan was available, and (c) the estimate incorporated new
      information from analyses of chinook salmon age and growth during the 1980s and
      1990s in Lake Michigan. We estimated that chinook salmon from Lake Michigan
      retain 53% of the PCBs that are contained within their food.

PMID- 12523417
TI  - Reactivity and mobility of new and old mercury deposition in a boreal forest
      ecosystem during the first year of the METAALICUS study. Mercury Experiment To
      Assess Atmospheric Loading In Canada and the US.
AB  - The METAALICUS (Mercury Experiment To Assess Atmospheric Loading In Canada and
      the US) project is a whole ecosystem experiment designed to study the activity,
      mobility, and availability of atmospherically deposited mercury. To investigate
      the dynamics of mercury newly deposited onto a terrestrial ecosystem, an enriched
      stable isotope of mercury (202Hg) was sprayed onto a Boreal forest subcatchment
      in an experiment that allowed us, for the first time, to monitor the fate of
      'new' mercury in deposition and to distinguish it from native mercury
      historically stored in the ecosystem. Newly deposited mercury was more reactive
      than the native mercury with respect to volatilization and methylation pathways.
      Mobility through runoff was very low and strongly decreased with time because of
      a rapid equilibration with the large native pool of "bound" mercury. Over one
      season, only approximately 8% of the added 212Hg volatilized to the atmosphere
      and less than 1% appeared in runoff. Within a few months, approximately 66% of
      the applied 202Hg remained associated with above ground vegetation, with the rest
      being incorporated into soils. The fraction of 202Hg bound to vegetation was much
      higher than seen for native Hg (<5% vegetation), suggesting that atmospherically
      derived mercury enters the soil pool with a time delay, after plants senesce and
      decompose. The initial mobility of mercury received through small rain events or
      dry deposition decreased markedly in a relatively short time period, suggesting
      that mercury levels in terrestrial runoff may respond slowly to changes in
      mercury deposition rates.

PMID- 12523418
TI  - Ultrafine PM emissions from natural gas, oxidation-catalyst diesel, and particle
      trap diesel heavy-duty transit buses.
AB  - This paper addresses how current technologies effective for reducing PM emissions
      of heavy-duty engines may affect the physical characteristics of the particles
      emitted. Three in-use transit bus configurations were compared in terms of
      submicron particle size distributions using simultaneous SMPS measurements under
      two dilution conditions, a minidiluter and the legislated constant volume sampler
      (CVS). The compressed natural gas (CNG)-fueled and diesel particulate filter
      (DPF)-equipped diesel configurations are two "green" alternatives to conventional
      diesel engines. The CNG bus in this study did not have an oxidation catalyst
      whereas the diesel configurations (with and without particulate filter) employed
      catalysts. The DPF was a continuously regenerating trap (CRT). Particle size
      distributions were collected between 6 and 237 nm using 2-minute SMPS scans
      during idle and 55 mph steady-state cruise operation. Average particle size
      distributions collected during idle operation of the diesel baseline bus
      operating on ultralow sulfur fuel showed evidence for nanoparticle growth under
      CVS dilution conditions relative to the minidiluter. The CRT effectively reduced
      both accumulation and nuclei mode concentrations by factors of 10-100 except
      under CVS dilution conditions where nuclei mode concentrations were measured
      during 55 mph steady-state cruise that exceeded baseline diesel concentrations.
      The CVS data suggest some variability in trap performance. The CNG bus had
      accumulation mode concentrations 10-100x lower than the diesel baseline but often
      displayed large nuclei modes, especially under CVS dilution conditions. Partly
      this may be explained by the lack of an oxidation catalyst on the CNG, but
      differences between the minidiluter and CVS size distributions suggest that
      dilution ratio, temperature-related wall interactions, and differences in tunnel
      background between the diluters contributed to creating nanoparticle
      concentrations that sometimes exceeded diesel baseline concentrations when
      driving under load. The results do not support use of CVS dilution methodology
      for ultrafine particle sampling, and, despite attention to collection of tunnel
      blanks in this study, results indicate that a protocol needs to be determined and
      prescribed for taking into account tunnel blank "emissions" to obtain meaningful
      comparisons between different technologies. Of critical importance is determining
      how temperature differences between tunnel blank and test cycle sampling compare
      in terms of background particle numbers. Total particle number concentrations for
      the minidiluter sampling point were not significantly different for the two
      alternative technologies when considering all the steady-cycle data collected.
      Concentrations ranged from 0.8 to 3 x 10(6) for the baseline bus operating on
      ultralow sulfur fuel, from 0.5 to 9 x 10(4) for the diesel bus equipped with the
      CRT filter, and from 1 to 8 x 10(4) particles/cc for the CNG bus.

PMID- 12523419
TI  - Gas-phase polychlorinated biphenyl and hexachlorocyclohexane concentrations near
      the Great Lakes: a historical perspective.
AB  - The Integrated Atmospheric Deposition Network (IADN) has been measuring gas
      phase, polychlorinated biphenyl (PCB) concentrations at sites near Lakes Michigan
      and Superior for over a decade. Data through 2000 were used in this study to
      investigate PCB temporal trends in the Great Lakes atmosphere. Decreasing trends
      were found at both sites, and half-lives of approximately 20 yr were calculated
      using IADN data. However, when these data were supplemented by historical data
      for Lakes Michigan and Superior dating back to 1977, half-lives dropped to 10 and
      6 yr, respectively. These latter half-lives agreed well with half-lives in other
      environmental compartments. Exponential curves fitted to the historical and IADN
      data indicated little decline in PCB concentrations in the basin since the mid
      1990s. A similar historical analysis of alpha-and gamma-hexachlorocyclohexane
      (HCH) data indicated that IADN data were the best predictor of trends, resulting
      in half-lives of around 4 yr for both compounds. Gamma-HCH concentrations,
      however, have shown little decline in recent years, most likely because of its
      continuing use. PCB and alpha-HCH temporal trends indicated that bans on these
      substances have helped to remove them from the atmosphere. This work also showed
      that decades of data may be necessary to properly interpret long-term temporal
      trends in gas-phase organochlorine concentrations.

PMID- 12523420
TI  - Latitudinal fractionation of polybrominated diphenyl ethers and polychlorinated
      biphenyls in frogs (Rana temporaria).
AB  - The flame retardant polybrominated diphenyl ethers (PBDEs) have become ubiquitous
      environmental pollutants. The environmental distribution of PBDEs is much less
      studied than that of the polychlorinated biphenyls (PCBs). To compare the
      environmental fate of the PCBs with their partial substitute, the PBDEs, common
      frogs (Rana temporaria)were collected along a approximately 1,500-km-long
      latitudinal gradient of the Scandinavian Peninsula and their livers analyzed for
      PCBs and PBDEs. Mean concentrations of total PCBs and BDE47 ranged from 9200 to
      92 900 and 30 to 120 ng kg(-1) fresh weight, respectively, whereas BDE99 was
      detected in less than 50% of the frogs. PCB concentrations were higher than that
      of the PBDEs, and the differences decreased in the northern latitudes. Moreover,
      the pollutant concentrations in frog livers were negative functions of latitude.
      The observed scatter and regression slopes imply several influencing factors
      (such as habitat, exposure route, uptake, metabolism, excretion, etc.) and
      indicate release events instead of the grasshopper effect Biological variables
      such as gender, age, body size, and lipid content did not influence pollutant
      concentrations in the frog livers. The total PCB and BDE47 concentrations in
      frogs were highly correlated. Hence, their environmental fate is analogous and
      our results highlight the need to examine the potential role of xenobiotics on
      amphibian populations.

PMID- 12523421
TI  - EXAFS and XANES studies of retention of copper and lead by a lignocellulosic
      biomaterial.
AB  - Lignocellulosic substrate (LS), which is a low cost biomaterial, has a strong
      complexing ability and can be used in the treatment of wastewaters as
      biosorbentto remove heavy metals. The speciation of copper and lead to this
      biomaterial has been studied by X-ray absorption spectroscopy. The copper(II) has
      a 6-coordinate structure with four oxygen atoms in the equatorial plane at 1.95 A
      and two in axial position at 2.35 A. In the case of lead a particularly low
      coordination number of about 3 has been obtained. The combination of extended X
      ray absorption fine structure (EXAFS) and X-ray absorption near edge structure
      (XANES) suggested that Cu and Pb are bound to the surface of LS through
      carboxylic moieties.

PMID- 12523422
TI  - Spectroscopic study of dinitrophenol herbicide sorption on smectite.
AB  - Sorption of two dinitrophenolic herbicides, 4,6-dinitro-o-cresol (DNOC) and 4,6
      dinitro-2-sec-butylphenol (DINOSEB) to smectite was studied using FTIR, HPLC, and
      quantum chemical methods. The high affinity of DNOC and DINOSEB for smectite
      surfaces was attributed to site-specific interactions with exchangeable cations
      and nonspecific van der Waals interactions with the siloxane surface. The
      positions of the nu(asym)(NO) and nu(sym)(NO) vibrational modes were perturbed by
      the exchangeable cations with similar changes occurring for both alkali and
      alkaline earth cations as a function of ionic potential. The cation-induced
      changes to the vibrational bands of the NO2 groups indicate that exchangeable
      metal cations are coordinated to -NO2 groups. Quantum chemical methods predicted
      a red-shift of the nu(asym)(NO) band and a corresponding blue-shift of the
      nu(sym)(NO) modes, as was observed experimentally. The nature of the smectite
      surface itself did not strongly influence the vibrational modes of sorbed DNOC or
      DINOSEB on the basis of a comparison of DNOC sorbed to three different smectites
      (K-SWy-2, K-SAz-1, and K-SHCa-1). FTIR spectra of DNOC and DINOSEB sorbed to a K
      SWy-2 smectite were studied quantitatively using a modified form of Beers law.
      The FTIR-derived sorption isotherm of DNOC sorbed to K-SWy-2 was in good
      agreement with the isotherm derived from HPLC measurements. The molar
      absorptivity value of DNOC sorbed to K-SWy-2 smectite was 1.43 x 10(7) cm2/mol in
      good agreement with literature values for nitroaromatics (average value of 1.72 x
      10(7) +/- 0.3 cm2/mol). On the basis of this value, the limit of detection using
      the FTIR method of approximately 5 microgDNOC g(clay) was determined. These two
      observations (sorption isotherms and molar absorptivity) provide a direct link
      between the macroscopic sorption results and the FTIR spectra.

PMID- 12523423
TI  - Biogenic phosphate minerals in manure: implications for phosphorus loss to
      surface waters.
AB  - Phosphorus (P) is present in waterways throughout the United States at
      concentrations that impair water quality. Agriculture, particularly livestock
      production, has been identified as a major cause of this impairment Excess manure
      P applied to croplands has increased P losses in runoff, leading to surface water
      eutrophication. We conducted a long-term (36-week) incubation with poultry and
      dairy manures applied to a silt loam soil to elucidate mechanisms controlling
      manure P loss to water. Manures were applied to supply the same total P rate to
      soils with different antecedent plant-available P concentrations (soil test P).
      There was a strong synergistic effect between dairy manure and soil test P on
      water extractable P, while soil test P did not affect P loss from poultry manure
      amended soils. Using scanning electron microscopy and energy dispersive X-ray
      spectroscopy, we found that poultry manure contained sparingly soluble calcium
      and magnesium phosphate minerals that controlled soil solution P concentrations,
      while dairy manure did not These minerals resemble other biogenic phosphate
      minerals. Our findings refute current assumptions that all manure P behaves
      similarly in soils and that organic forms control manure-soil P loss to water.

PMID- 12523424
TI  - Direct evidence of atmospheric secondary organic aerosol formation in forest
      atmosphere through heteromolecular nucleation.
AB  - Atmospheric aerosols play a central role in climate and atmospheric chemistry.
      Organic matter frequently composes aerosol major fraction over continental areas.
      Reactions of natural volatile organic compounds, with atmospheric oxidants, are a
      key formation pathway of fine particles. The gas and particle atmospheric
      concentration of organic compounds directly emitted from conifer leaf
      epicuticular wax and of those formed through the photooxidation of alpha- and
      beta-pinene were simultaneously collected and measured in a conifer forest by
      using elaborated sampling and GC/ MS techniques. The saturation concentrations of
      acidic and carbonyl photooxidation products were estimated, by taking into
      consideration primary gas- and particle-phase organic species. Primary organic
      aerosol components represented an important fraction of the atmospheric gas-phase
      organic content Consequently, saturation concentrations of photooxidation
      products have been lowered facilitating new particle formation between molecules
      of photooxidation products and semi-volatile organic compounds. From the measured
      concentrations of the above-mentioned compounds, saturation concentrations
      (Csat,i) of alpha- and beta-pinene photooxidation products were calculated for
      nonideal conditions using a previously developed absorptive model. The results of
      these calculations indicated that primarily emitted organic species and ambient
      temperature play a crucial role in secondary organic aerosol formation.

PMID- 12523425
TI  - Low temperature XAFS investigation on the lutetium binding changes during the 2
      line ferrihydrite alteration process.
AB  - The time dependent changes of Lu speciation (used as Am(III) homologue),
      initially sorbed onto 2-line ferrihydrite at pH 5.9, during tempering (70 degrees
      C) to stable crystalline transformation products, goethite and hematite, is
      studied. Microscopies (AFM, SEM), XRD and FTIR spectroscopy confirm
      transformation to both goethite and hematite, with a predominance of hematite.
      XRD investigation of another transformation series at pH 8.0 (75 degrees C,
      [Lu(III)initial] 7 times higher) shows that the cell volume of hematite
      increases, suggesting the incorporation of Lu in the crystal structure. Extended
      X-ray absorption fine structure (EXAFS) (pH 5.9 series, 70 degrees C) reveals a
      shortening of the Lu-O bond distance and an increase in asymmetry of the first
      shell with increasing tempering time in the intermediate temper time samples. The
      intensity of the second peak in the Fourier transform (FT) of the EXAFS increases
      and splits into two components. The EXAFS data of the end product can be modeled
      well using a hematite-like cluster, with an isotropic expansion of distances to
      account for incorporation of Lu into the hematite structure. These results
      demonstrate that the Lu is incorporated in the crystal lattice of the
      transformation product, as opposed to being occluded or remaining a sorbed
      species on the surface.

PMID- 12523426
TI  - Disaggregation kinetics of a peat humic acid: mechanism and pH effects.
AB  - Fluorescence correlation spectroscopy was used to study the disaggregation
      kinetics of a peat humic acid (PPHA) at several pH. FCS measures diffusion
      coefficients of fluorescent molecules and aggregates, thus allowing for the
      determination of disaggregation rates with a temporal resolution of seconds to
      minutes. Disaggregation was initiated by dilution of a peat concentrate
      consisting of a mixture containing 80% large aggregates (average hydrodynamic
      radius, rH, of about 300 nm) and free monomers (average rH of about 1 nm). Upon
      dilution at different pH values, aggregate size decreased, and the proportion of
      free monomers in solution increased until complete disaggregation occurred. The
      mechanism appeared to involve the release of monomers from the surface of the
      aggregates. The pH markedly affected the disaggregation rate. Complete
      disaggregation took 1 month at pH 3.6, took less than 1 h at pH 5.6, and was
      extremely rapid in alkaline solutions. The results suggested that at least two
      processes were operating in parallel with the overall rate being the sum of both
      processes. At pH higher than 4.5, the disaggregation rate increased more than 3
      orders of magnitude per pH unit increase. For concentrations lower than 30 mg L(
      1), the equilibrium condition for the PPHA was complete disaggregation even for a
      pH as low as 3.6.

PMID- 12523427
TI  - Field demonstration of successful bioaugmentation to achieve dechlorination of
      tetrachloroethene to ethene.
AB  - A laboratory microcosm study and a pilot scale field test were conducted to
      evaluate biostimulation and bioaugmentation to dechlorinate tetrachloroethene
      (PCE) to ethene at Kelly Air Force Base. The site groundwater contained about 1
      mg/L of PCE and lower amounts of trichloroethene (TCE) and cis-1,2-dichloroethene
      (cDCE). Laboratory microcosms inoculated with soil and groundwater from the site
      exhibited partial dechlorination of TCE to cDCE when amended with lactate or
      methanol. Following the addition of a dechlorinating enrichment culture, KB-1,
      the chlorinated ethenes in the microcosms were completely converted to ethene.
      The KB-1 culture is a natural dechlorinating microbial consortium that contains
      phylogenetic relatives of Dehalococcoides ethenogenes. The ability of KB-1 to
      stimulate biodegradation of chlorinated ethenes in situ was explored using a
      closed loop recirculation cell with a pore volume of approximately 64,000 L The
      pilot test area (PTA) groundwater was first amended with methanol and acetate to
      establish reducing conditions. Under these conditions, dechlorination of PCE to
      cDCE was observed. Thirteen liters of the KB-1 culture were then injected into
      the subsurface. Within 200 days, the concentrations of PCE, TCE, and cis-1,2-DCE
      within the PTA were all below 5 microg/L, and ethene production accounted for the
      observed mass loss. The maximum rates of dechlorination estimated from field date
      were rapid (half-lives of a few hours). Throughout the pilot test period,
      groundwater samples were assayed for the presence of Dehalococcoides using both a
      Dehalococcoides-specific PCR assay and 16S rDNA sequence information. The
      sequences detected in the PTA after bioaugmentation were specific to the
      Dehalococcoides species in the KB-1 culture. These sequences were observed to
      progressively increase in abundance and spread downgradient within the PTA. These
      results confirm that organisms in the KB-1 culture populated the PTA aquifer and
      contributed to the stimulation of dechlorination beyond cDCE to ethene.

PMID- 12523428
TI  - Photodegradation of RDX in aqueous solution: a mechanistic probe for
      biodegradation with Rhodococcus sp.
AB  - Recently we demonstrated that Rhodococcus sp. strain DN22 degraded hexahydro
      1,3,5-trinitro-1,3,5-triazine (RDX) (1) aerobically via initial denitration
      followed by ring cleavage. Using UL 14C-[RDX] and ring labeled 15N-[RDX]
      approximately 30% of the energetic chemical mineralized (one C atom) and 64%
      converted to a dead end product that was tentatively identified as 4-nitro-2,4
      diaza-butanal (OHCHNCH2NHNO2). To have further insight into the role of initial
      denitration on RDX decomposition, we photolyzed the energetic chemical at 350 nm
      and pH 5.5 and monitored the reaction using a combination of analytical
      techniques. GC/ MS-PCI showed a product with a [M+H] at 176 Da matching a
      molecular formula of C3H5N5O4 that was tentatively identified as the initially
      denitrated RDX product pentahydro-3,5-dinitro-1,3,5-triazacyclohex-1-ene (II).
      LC/MS (ES-) showed that the removal of RDX was accompanied by the formation of
      two other key products, each showing the same [M-H] at 192 Da matching a
      molecular formula of C3H7N5O5. The two products were tentatively identified as
      the carbinol (III) of the enamine (II) and its ring cleavage product
      O2NNHCH2NNO2CH2NHCHO (IV). Interestingly, the removal of III and IV was
      accompanied by the formation and accumulation of OHCHNCH2NHNO2 that we detected
      with strain DN22. At the end of the experiment, which lasted 16 h, we detected
      the following products HCHO, HCOOH, NH2CHO, N2O, NO2-, and NO3-. Most were also
      detected during RDX incubation with strain DN22. Finally, we were unable to
      detect any of RDX nitroso products during both photolysis and incubation with the
      aerobic bacteria, emphasizing that initial denitration in both cases was
      responsible for ring cleavage and subsequent decomposition in water.

PMID- 12523429
TI  - Factors controlling the bioavailability of ingested methylmercury to channel
      catfish and Atlantic sturgeon.
AB  - The bioavailability of ingested methylmercury (CH3Hg(III) was investigated in
      vitro using the gastric and intestinal fluids of channel catfish, Ictalurus
      punctatus, and Atlantic sturgeon, Acipenser oxyrinchus. Gastric fluid collected
      from each species was incubated with CH3Hg(II)-spiked sediment or bloodworms,
      after which the intestinal fluid of each species was added and incubated further.
      The proportion of CH3Hg(II) solubilized from bloodworms and sediment appeared to
      be controlled by complexation to amino acids in both the stomach and the
      intestinal fluids during the digestive process,with the more thorough digestion
      of bloodworm organic material enhancing CH3Hg(II) solubilization. A greater
      proportion of CH3Hg(II) was solubilized by the sturgeon fluids compared to the
      catfish fluids, especially for the sediment incubations. These differences
      corresponded to the relative amount of amino acids in the fluids of these fish. A
      comparison of the catfish gastrointestinal solubilization incubations and a CH3
      Hg(II) bioaccumulation experiment with bloodworms revealed that the
      solubilization incubations may be a reasonable surrogate measurement of the
      bioavailability of CH3Hg(II) to fish. Overall, it appears that digestive
      processes is the most important controlling factor in the bioavailability of
      CH3Hg(II) to fish.

PMID- 12523430
TI  - Measurement of heavy metal speciation over redox gradients in natural water
      sediment interfaces and implications for uptake by benthic organisms.
AB  - The sediment or fauna incubation experiment (SOFIE) is an experimental research
      tool that was developed to analyze concentrations and chemical speciation of
      heavy metals in pore waters of natural, undisturbed sediments or water-sediment
      interfaces over time, while simultaneously conducting exposure tests with
      sediment-dwelling organisms. In this way, concentrations of chemical species are
      directly linked to accumulation by biota. It is shown that discrete gradients of
      redox-sensitive metals and nutrients occur over very small intervals. These
      gradients differ from those of free metal ion activities. Speciation affects the
      uptake of metals by sediment-dwelling organisms, which, in their turn, have a
      significant effect on metal speciation. With reaction kinetics that differ per
      metal, uptake of metals by organisms from the water phase may be hindered (e.g.,
      Cu, Zn) or promoted (e.g., Ni, As). Time-varying exposure concentrations of
      metals were incorporated in uptake and elimination models. Body concentrations of
      Cd, Cu, Ni, and Zn in the aquatic oligochaete Limnodrilus could best be described
      by the time-varying free ion concentration in the overlying water. Body
      concentrations of As and Pb were best described by sediment pore water
      concentrations. It is concluded that SOFIE provides the necessary experimental
      tool to support, in a mechanistic way, environmental risk assessments of
      contaminants.

PMID- 12523431
TI  - Use of compound-specific stable carbon isotope analyses to demonstrate anaerobic
      biodegradation of MTBE in groundwater at a gasoline release site.
AB  - Currently it is unclear if natural attenuation is an appropriate remedial
      approach for groundwater impacted by methyl tertiary butyl ether (MTBE). Site
      characterization data at most gasoline release sites are adequate to evaluate
      attenuation in MTBE concentrations over time or distance. But, demonstrating
      natural biodegradation of MTBE requires laboratory microcosm studies, which could
      be expensive and time-consuming. Recently, compound-specific carbon isotope ratio
      analyses (13C/12C expressed in delta13C notation) have been used to demonstrate
      aerobic biodegradation of MTBE in laboratory incubations. This study explored the
      potential of this approach to distinguish MTBE biodegradation from other abiotic
      processes in an anaerobic groundwater plume that showed extensive decrease in
      MTBE concentrations. To our knowledge, this is the first study to use delta13C of
      MTBE data in groundwater and laboratory microcosms to demonstrate anaerobic
      biodegradation of MTBE. The delta13C of MTBE in monitoring wells increased by up
      to 31 per thousand (-25.5 per thousand to +5.5 per thousand) along with a 40-fold
      decrease in MTBE concentrations. Anaerobic incubations in laboratory microcosms
      indicated up to 20-fold reduction in MTBE concentrations with a corresponding
      increase in delta13C of MTBE of up to 33.4 per thousand (-28.7 per thousand to
      +4.7 per thousand) in live microcosms. Little enrichment was observed in
      autoclaved controls. These results demonstrate that anaerobic biodegradation was
      the dominant natural attenuation mechanism for MTBE at this site. The estimated
      isotopic enrichment factors (epsilon(field) = -8.10 per thousand and epsilon(lab)
      = -9.16 per thousand) were considerably larger than the range (-1.4 per thousand
      to -2.4 per thousand) previously reported for aerobic biodegradation of MTBE in
      laboratory incubations. These observations strongly suggest that delta13C of MTBE
      could be potentially useful as an "indicator" of in-situ MTBE biodegradation.

PMID- 12523432
TI  - Abiotic reductive dechlorination of chlorinated ethylenes by iron-bearing soil
      minerals. 1. Pyrite and magnetite.
AB  - Abiotic reductive dechlorination of chlorinated ethylenes (tetrachloroethylene
      (PCE), trichloroethylene (TCE), cis-dichloroethylene (cis-DCE), and vinyl
      chloride (VC)) by pyrite and magnetite was characterized in a batch reactor
      system. Dechlorination kinetics was adequately described by a modified Langmuir
      Hinshelwood model that includes the effect of a decreasing reductive capacity of
      soil mineral. The kinetic rate constant for the reductive dechlorination of
      target organics at reactive sites of soil minerals was in the range of 0.185 (+/-
      0.023) to 1.71 (+/- 0.06) day(-1). The calculated specific reductive capacity of
      soil minerals for target organics was in the range of 0.33 (+/- 0.02) to 2.26 (+/
      0.06) microM/g and sorption coefficient was in the range of 0.181 (+/- 0.006) to
      0.7 (+/- 0.022) mM(-1). Surface area-normalized pseudo-first-order initial rate
      constants for target organics by pyrite were found to be 23.5 to 40.3 times
      greater than those by magnetite. Target organics were mainly transformed to
      acetylene and small amount of chlorinated intermediates, which suggests that beta
      elimination was the main dechlorination pathway. The dechlorination of VC
      followed a hydrogenolysis pathway to produce ethylene and ethane. The addition of
      Fe(II) increased the dechlorination rate of cis-DCE and VC in magnetite
      suspension by nearly a factor of 10. The results obtained in this research
      provide basic knowledge to better predict the fate of chlorinated ethylenes and
      to understand the potential of abiotic processes in natural attenuation.

PMID- 12523433
TI  - Formation of methane sulfinic acid in the gas-phase OH-radical initiated
      oxidation of dimethyl sulfoxide.
AB  - Dimethyl sulfoxide (CH3S(O)CH3: DMSO) is an important product of dimethyl sulfide
      (CH3SCH3: DMS) photooxidation. The mechanism of the OH-radical initiated
      oxidation of DMSO is still highly uncertain and a major aim of recent studies has
      been to establish if methane sulfinic acid (CH3S(O)OH: MSIA) is a major reaction
      product In the present work the products of the OH-radical gas-phase oxidation of
      dimethyl sulfoxide have been investigated in the absence and presence of NOx All
      experiments were performed in a 1,080 L reaction chamber in 1,000 mbar synthetic
      air at 284 +/- 2 K using long-path FT-IR spectroscopy and ion chromatography to
      monitor and quantify reactants and reaction products. Formation of methane
      sulfinic acid in high yield (80-99%) was observed in both in the absence and
      presence of NOx, and the results support that it is the major primary reaction
      product Other products observed included dimethyl sulfone (CH3S(O)2CH3: DMSO2),
      sulfur dioxide (SO2), methane sulfonic acid (CH3S(O)2OH: MSA), and methane
      sulfonyl peroxynitrate (CH3S(O)2OONO2: MSPN). The formation behavior of these
      products is in line with their source being mainly secondary production via
      oxidation of a primary product, i.e. MSIA.

PMID- 12523434
TI  - Geochemistry of Cd, Cr, and Zn in highly contaminated sediments and its
      influences on assimilation by marine bivalves.
AB  - We tested the controls of metal geochemistry in sediments collected from an
      extremely contaminated Chinese bay on metal assimilation by marine mussels and
      clams. Metal speciation in the contaminated sediments, quantified by the Tessier
      operational extraction method, was significantly dependent on metal
      concentrations in the sediments. The fractions of Cd in the easily exchangeable
      and carbonate phases increased, while the reducible and residue phases decreased
      with increasing Cd concentration. The majority (72-91%) of Cr was associated with
      the residue component with the remainder of Cr in the organic matter and
      reducible phases. Zn in carbonate phase increased, whereas in the organic matter
      and residue phases it decreased with increasing Zn concentration. The
      bioavailability of Cd, Cr, and Zn to marine green mussels (Perna viridis) and
      clams (Ruditapes philippinarum) was quantified using radiotracer spiked technique
      with concurrent measurements of speciation of spiked metals. There was a
      significant correlation between the Cd assimilation efficiency (AE) by both
      mussels and clams and Cd partitioning in the easily exchangeable and reducible
      phases. In contrast to previous studies, a negative correlation was found between
      the Cd AE and its total concentration in sediment, likely caused by the
      saturation of Cd binding sites in the gut or by its antagonistic interaction with
      a very high Zn concentration in these collected sediments. In contrast, there was
      no significant correlation between the AEs of Cr or Zn and any of their
      geochemical phases or their concentrations. The metal AEs were further quantified
      by experimentally manipulating different concentrations and ratios of acid
      volatile sulfide (AVS) and simultaneously extractable metals (SEM). There was no
      statistically significant relationship between the AEs of the three metals and
      the concentrations of AVS and SEM or [SEM-AVS]. Geochemical controls on metal
      assimilation from contaminated sediment are therefore only relatively apparent
      for Cd. The influences of metal speciation on metal bioavailability can be
      confounded by the degree to which sediments are contaminated with metals.

PMID- 12523435
TI  - Reduction of oxamyl and related pesticides by FeII: influence of organic ligands
      and natural organic matter.
AB  - The reduction of oxamyl and related oxime carbamate pesticides (OCPs; methomyl
      and aldicarb) by FeII is an important pathway for the degradation of these
      compounds in soil and groundwater. A series of batch kinetic experiments was
      carried out to assess the effects that selected carboxylate and aminocarboxylate
      ligands have on these reactions. In the absence of FeII, no OCP reduction by the
      ligands is observed. In the presence of FeII, the rate of OCP reduction varies by
      several orders of magnitude and can be described by the expression k(red) =
      [FeII]sigma(i)k(i)alpha(i) where k(red) is the observed pseudo-first-order rate
      constant for OCP reduction, [FeII] is the total FeII concentration, alpha(i) is
      the fraction of each FeII species in solution, and k(i) is the second-order rate
      constant for OCP reduction by each FeII species. The reactivity of individual
      FeII species is dependent upon the standard one-electron reduction potential of
      the corresponding FeIII/FeII redox couple (E(H)o) and the availability of inner
      sphere FeII coordination sites for bonding with Lewis base donor groups within
      the OCP structure. A linear free energy relationship is proposed. Kinetic
      measurements demonstrate that natural organic matter from the Great Dismal Swamp
      facilitates OCP reduction by FeII in the same manner as the individual organic
      ligands. Results from this study improve our understanding of the pathways and
      rates of pesticide degradation in reducing subsurface environments, especially
      those rich in organic matter.

PMID- 12523436
TI  - Probabilistic analysis of during cycle-based highway vehicle emission factors.
AB  - A probabilistic methodology for quantifying intervehicle variability and fleet
      average uncertainty in highway vehicle emission factors is developed. The
      methodology features the use of empirical distributions of emissions measurement
      data to characterize variability and the use of bootstrap simulation to
      characterize uncertainty. For the base emission rate as a function of mileage
      accumulation under standard conditions, a regression-based approach was employed
      in which the residual error terms were included in the probabilistic analysis.
      Probabilistic correction factors for different driving cycles, ambient
      temperature, and fuel Reid vapor pressure (RVP) were developed without
      interpolation or extrapolation of available data. The method was demonstrated for
      tailpipe carbon monoxide, hydrocarbon, and nitrogen oxides emissions for a
      selected light-duty gasoline vehicle technology. Intervehicle variability in
      emissions was found to span typically 2 or 3 orders of magnitude. The uncertainty
      in the fleet average emission factor was as low as +/- 10% for a 95% probability
      range, in the case of standard conditions, to as much as -90% to +280% when
      correction factors for alternative driving cycles, temperature, and RVP are
      applied. The implications of the results for method selection and for decision
      making are addressed.

PMID- 12523437
TI  - Thermodynamics of carbon dioxide hydrate formation in media with broad pore-size
      distributions.
AB  - Equilibrium pressures for the dissociation of carbon dioxide hydrates confined in
      silica gel pores of nominal radii 7.5, 5.0, and 3.0 nm were measured over a wide
      temperature range and were observed to be higher than those for bulk carbon
      dioxide hydrate. Models that have been previously reported in the literature are
      used to determine the pore radius involved in each equilibrium associated with
      these data, exactly reproducing the experimental equilibrium pressure. Based on
      these models, pore volume distributions are reconstructed and compared to those
      obtained from nitrogen desorption isotherms. This comparison indicates that in
      the nominal 7.5 nm pores the hydrate formed nearly uniformly in the available
      pores, while in the nominal 5.0 and 3.0 nm pores it did not.

PMID- 12523438
TI  - Uncertainties in charring correction in the analysis of elemental and organic
      carbon in atmospheric particles by thermal/optical methods.
AB  - Thermal/optical methods are widely used in the determination of aerosol organic
      carbon (OC) and elemental carbon (EC) collected on quartz filters. A fraction of
      OC undergoes charring to form pyrolytically generated EC (PEC) during thermal
      analysis. The correct speciation of OC and EC in thermaVoptical methods depends
      on one of the following two assumptions: (1) PEC evolves before native EC evolves
      in the analysis or (2) PEC and native EC have the same apparent light absorption
      coefficient (sigma) at the monitoring light wavelength. Neither of these
      assumptions has actually ever been checked or tested. The first assumption is
      invalidated by the observation that the combustion of PEC overlaps that of native
      EC despite multiple stepwise combustion at temperatures ranging from 575 to 910
      degrees C. An examination of sigma versus EC evolution indicates that the sigma
      values of PEC and EC are not the same in most cases and the a value of PEC is not
      constant during a single thermal analysis. The second assumption is thus invalid
      as well. The measured EC concentrations can either overestimate or underestimate
      the true native EC concentrations depending on the relative magnitude of the a
      values of the PEC and native EC at the point where the instrument sets the EC/OC
      split line. Both over- and underestimation have been observed in real aerosol
      samples. The unequal a values of PEC and EC also explain that different
      temperature programs, when employed to analyze the same filter samples,
      systematically yield different EC and OC concentrations. Our findings imply that
      minimizing charring improves the accuracy of the EC/OC split in thermal/optical
      methods.

PMID- 12523439
TI  - Development and evaluation of a personal particulate organic and mass sampler.
AB  - Accurate measurement of personal exposure to particulate matter and its
      constituents requires samplers that are accurate, compact, lightweight,
      inexpensive, and convenient to use. The personal particulate organic and mass
      sampler (PPOMS) has been developed to meet these criteria. The PPOMS uses
      activated carbon-impregnated foam as a combined 2.5-microm size-selective inlet
      and denuder for assessment of fine particle mass and organic carbon. Proof of the
      PPOMS concept has been established by comparing mass and organic carbon in
      particles collected with collocated samplers in Seattle, at a central outdoor
      site, and in residences. Daily particulate mass concentrations averaged 10.0 +/-
      5.2, 12.0 +/- 5.3, and 11.2 +/- 5.1 microg m(-3) for the Federal Reference
      Method, the Harvard Personal Exposure Monitor, and the PPOMS, respectively, for
      10 24-h sampling periods. During a series of PM2.5 indoor organic carbon (OC)
      measurements from single quartz filters, the apparent indoor OC averaged 7.7 +/-
      0.8 microg of C m(-3), which was close to the indoor PM2.5 mass from collocated
      Teflon filters (7.3 +/- 2.3 microg of C m(-3)), indicating the presence of a
      large positive OC artifact. In collocated measurements, the PPOMS eliminated this
      artifact just as well as the integrated gas and particle sampler that
      incorporated a macroreticular polystyrene-divinylbenzene (XAD-4) resin-coated
      denuder, yielding OC concentrations of 2.5 +/- 0.4 and 2.4 +/- 1.0 microg of C m(
      3), respectively. Thermal analysis for OC indicated that the indoor positive
      artifact was due to adsorption of gas-phase semivolatile organic compounds
      (SVOC). This study shows that the PPOMS design provides a 2.5-microm size
      selective inlet that also prevents the adsorption of gas-phase SVOC onto quartz
      filters, thus eliminating the filter positive artifact The PPOMS meets a
      significant current challenge for indoor and personal sampling of particulate
      organic carbon. The PPOMS design can also simplify accurate ambient sampling for
      PM2.5.

PMID- 12523440
TI  - Low-temperature thermal decomposition of dioxin-like compounds in fly ash:
      combination of chemical analysis with in vitro bioassays (EROD and DR-CALUX).
AB  - To investigate the dechlorination of fly ash during low-temperature treatment
      under oxygen-deficient conditions (thermocatalyic treatment or Hagenmaier
      process), six fly ash samples from six different incineration plants were treated
      in a laboratory experiment or in the actual plant, either under ideal (400
      degrees C, 120 min) or intermediate (300 degrees C, 30 min) conditions. The aim
      of the present study was to confirm the decrease in the I-TEQ (international
      toxicity equivalency) of polychlorinated dibenzo-p-dioxins/-furans (PCDD/Fs) and
      coplanar polychlorinated biphenyls (co-PXBs) and, also for the first time, the
      decrease in the sum of dioxin-like toxicity (bioassay- or bio-TEQ) of all kinds
      of other dioxin-like Ah receptor agonists (such as PXDD/Fs, PXBs, PXN, X = Br, F)
      measured by two state-of-the-art cell-based Ah receptor-dependent bioassays:
      H4IIE-Ethoxy-Resorufin-o-Deethylase (EROD) and H4IIE-luc/DR-Chemical Activated
      Luciferase expression (DR-CALUX). The treatment efficiency was calculated on the
      basis of the reduction in the I-TEQ and bio-TED values. For these fly ash
      samples, the treatment efficiency, as measured by chemical analysis, was higher
      than 99%, and 85%-99%, in the case of the bio-TED values, indicating that these
      Ah receptor binding toxic compounds were sufficiently decomposed. Bio-TEQ values
      for untreated fly ash samples (n = 6) were on average 1.2 times (range 0.7-1.9),
      for the H4IIE-EROD assay, and 2.8 times (1.1-4.9), for the DR-CALUX assay, higher
      than I-TEQ values measured by chemical analyses (sum of PCDD/Fs and co-PCBs). In
      the case of these fly ash samples treated under ideal conditions and therefore
      low in contaminants, the bio-TEQ values were on average 1.4 times (range 0.9
      1.8), for the H4IIE-EROD assay, and 5.1 times (range 1.2-12), for the DR-CALUX
      assay, higher than the I-TEQ values.

PMID- 12523441
TI  - Study of the effects of particle-phase carbon on the gas/particle partitioning of
      semivolatile organic compounds in the atmosphere using controlled field
      experiments.
AB  - A controlled field experiment (CFE) methodology with a filter/sorbent sampler was
      used to minimize artifact effects when measuring values of the gas/particle (G/P)
      partitioning constant (Kp, m3 microg(-1)) for semivolatile organic compounds
      (SOCs) in the atmosphere. CFE sampling was conducted at three different locations
      (Beaverton, OR; Denver, CO; and Hills, IA). Kp values were measured for a series
      of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated dibenzodioxins and
      dibenzofurans (PCDD/Fs). To examine the possible effects on the G/P partitioning
      of the amounts of organic material (om) phase, organic carbon (OC), and elemental
      carbon (EC) in the sampled particulate material, the measured Kp values were
      normalized by the aerosol mass fractions f(om), f(OC), and f(EC) according to Kp/
      f(om), Kp/f(OC), and Kp/f(EC). Using a log-log format, the resulting normalized
      values were all found to be more highly correlated with the subcooled liquid
      vapor pressure p(L)o than were the unnormalized Kp values. For the PAHs,the one
      parameter model assuming Kp = Kp,OC f(OC) yielded only slightly less variability
      in the predicted Kp values than did the one-parameter model Kp = Kp,EC f(EC). The
      two-parameter model Kp = Kp,OC f(OC) + Kp,EC f(EC) was found to provide only
      small improvements over each of the one-parameter models. Overall, the data are
      more consistent with an absorptive mechanism of partitioning to the particulate
      material but do not rule out some role for adsorption to particle surfaces. The
      data suggest that small amounts of organic carbon (f(OC) approximately 0.02) can
      have significant effects on the G/P partitioning of SOCs.

PMID- 12523443
TI  - Enhanced contact of cosolvent and DNAPL in porous media by concurrent injection
      of cosolvent and air.
AB  - Dense nonaqueous phase liquid (DNAPL) contamination is a major environmental
      problem. Cosolvent flooding is proposed as a remedial alternative to water
      flooding. The efficacy of cosolvent flooding is a function of the degree of
      contact between the injected remedial fluid and the resident DNAPL Poor contact
      may result from remedial fluids traveling in preferential flow paths which bypass
      trapped DNAPL Thus, the motivation for this study was to use the preferential
      flow of air in porous media to enhance contact between the injected cosolvent and
      resident DNAPL The study evaluated concurrent injection of cosolvent and air to
      improve the spatial extent of DNAPL removal in porous media. A 70% ethanol/30%
      water (v/v) cosolvent was injected simultaneously with air into a micromodel
      containing residual tetrachloroethylene (PCE). Double drainage displacement was
      observed as a dominant DNAPL removal mechanism in the initial period of the
      cosolvent-air flooding (i.e., gas displaced PCE that displaced water). The
      residual PCE residing in the preferential paths traversed by air was readily
      displaced. In addition to this initial PCE mobilization, air flowing through the
      preferential flow paths displaced cosolvent from these paths into other flow
      paths and facilitated dissolution of PCE.

PMID- 12523442
TI  - Environmental remediation by an integrated microwave/UV illumination technique.
      3. A microwave-powered plasma light source and photoreactor to degrade pollutants
      in aqueous dispersions of TiO2 illuminated by the emitted UV/visible radiation.
AB  - The characteristic features of a novel double-quartz cylindrical plasma
      photoreactor (DQCPP) were assessed by examining the photodegradation of rhodamine
      B dye (RhB+) in aqueous TiO2 dispersions irradiated simultaneously by both
      microwave radiation and UV/visible radiation emitted from a microwave-powered
      (MW, 2.45 GHz) electrodeless mercury lamp. The features of the DQCPP lamp are
      given and discussed in terms of the experimental output UV energy in the
      wavelength ranges 210-300 and 310-400 nm for applied MW powers from 74 to 621 W.
      The DQCPP and a water-cooled DQCPP reactor absorbed more than 50% MW radiation
      (50-88 and 50-75%, respectively). The emitted light irradiance scaled sublinearly
      with applied MW power. Relative to the DQCPP lamp, loss of irradiance by the
      water-cooled DQCPP lamp was approximately 28-46% at 250 nm and approximately 41
      58% at 360 nm in the range of MW power used. The smallest loss occurred at 178.9
      W at which the degradation of RhB+ was subsequently examined by UV/visible
      spectroscopy and by total organic carbon analyses. Highly intense mercury lines
      were seen at 365, 404, 435, 546, and 579 nm (those below 365 nm were more than 10
      times weaker). About 80% of the RhB+ solution was photomineralized after 60 min
      of irradiation of the aqueous RhB+/TiO2 dispersion with the DQCPP lamp; no UV/
      visible spectral features of RhB+ were evident at wavelengths below 250 nm after
      30 min. Possible effects of microwave radiation and temperature on the
      degradative process are described.

PMID- 12523444
TI  - Characteristics of a self-forming dynamic membrane coupled with a bioreactor for
      municipal wastewater treatment.
AB  - A self-forming dynamic membrane (SFDM) method that used the biomass layer formed
      on a coarse mesh to effect solid-liquid separation was proposed. A 100-microm
      Dacron mesh material was used to make the SFDM modules. A SFDM coupled bioreactor
      (SFDMBR) was tested to treat actual municipal wastewater, and the performance and
      mechanisms of the SFDM were investigated. The SFDMBR worked by gravity
      filtration, and the water head drop was generally <5 cm. The effluent suspended
      solid concentrations were undetectable in most cases, and the COD and NH3 N
      removal efficiencies averaged 84.2% and 98.03%, respectively. An aeration in situ
      was adequate for cleaning the clogged modules, and the SFDM was readily and
      quickly re-formed. The biomass layer of the SFDM consisted of a cake layer and a
      gel layer. The gel layer had structures like conventional membranes and acted the
      key role in the SFDM. The permeability of the used mesh attached to the gel layer
      could be improved because the gel layer made the filtration surface more
      hydrophilic.

PMID- 12523445
TI  - Photocatalytic degradation of 2-phenethyl-2-chloroethyl sulfide in liquid and gas
      phases.
AB  - This work explores the ability of photocatalysis to decontaminate water and air
      from chemical warfare agent mustard using its simulant 2-phenethyl 2-chloroethyl
      sulfide (PECES). PECES like mustard slowly dissolves in water with hydrolysis,
      forming 2-phenethyl 2-hydroxyethyl sulfide (PEHES). Irradiation of TiO2
      suspension containing PECES with the unfiltered light of a mercury lamp (lambda >
      or = 254 nm) decomposed all PECES mostly via photolysis. Reaction under filtered
      light (lambda > 300 nm) proceeds mainly photocatalytically and requires longer
      time. Sulfur from starting PECES is completely transformed into sulfuric acid at
      the end of the reaction. Detected volatile, nonvolatile, surface products, and
      the suggested scheme of degradation are reported. The main volatile products are
      styrene and benzaldehyde, nonvolatile--hydroxylated PEHES, surface--2-phenethyl
      disulfide. Photolysis of PECES produced the same set of volatile products as
      photocatalysis. Photocatalytic degradation of gaseous PECES in air results in its
      mineralization but is accompanied by TiO2 deactivation. The highest rate of
      mineralization with minimum deactivation was observed at about room temperature
      and a water concentration of 27,500 ppm. No gaseous products except CO2 were
      detected. The main extracted surface product was styrene. It was concluded that
      PECES photocatalytic degradation proceeds mainly via C-S bond cleavage and
      further oxidation of the products. Hydrolysis of the C-S bond was detected only
      in gas-phase photocatalytic degradation. The quantum efficiency of gas-phase
      degradation (0.28%) was much higher than that of liquid-phase degradation
      (0.008%). The results demonstrate the ability of photocatalysis to decontaminate
      an aqueous and especially an air environment

PMID- 12523446
TI  - Evaluation of on-board diagnosis methods for three-way catalytic converters.
AB  - On-board diagnosis (OBD) aims at detecting malfunctions of emission-related
      components of road vehicles. It is required by legislation in United States and
      the European Union, as it is considered to be beneficial for the reduction of
      vehicle-related air pollution. On-board diagnosis of the catalytic converter is a
      challenging task, as it relies on indirect assessments of catalyst activity.
      Several methods have been proposed for catalyst diagnosis, presenting a varying
      degree of correlation between the quantities used as OBD indexes and the actual
      tailpipe emissions. This paper evaluates two methods, with the support of
      mathematical modeling; in the first one, which is commonly used by vehicle
      manufacturers, malfunction detection relies on the oxygen storage properties of
      the catalyst, while in the second, detection relies on the heat released by the
      chemical reactions in the catalyst. Both are found to be sufficient for the
      diagnosis of catalytic converters for current legislation requirements. However,
      the thermal method presents higher sensitivity to low levels of catalyst
      deactivation and could therefore be more suitable for diagnosis of future, ultra
      low-emitting vehicles.

PMID- 12523447
TI  - Body image dissatisfaction: gender differences in eating attitudes, self-esteem,
      and reasons for exercise.
AB  - Two hundred and thirty-five adolescents completed a questionnaire on the subject
      of eating attitudes, self-esteem, reasons for exercise, and their ideal versus
      current body size and shape. As predicted, boys were as likely to want to be
      heavier as lighter, whereas very few girls desired to be heavier. Only girls
      associated body dissatisfaction with the concept of self-esteem. Male self-esteem
      was not affected by body dissatisfaction. Specific reasons for exercise were
      found to correlate with low self-esteem and disordered eating, regardless of sex.
      The results are discussed in relation to burgeoning published research in this
      area.

PMID- 12523448
TI  - The influence of belief that a car crashed on witnesses' estimates of civilian
      and police car speed.
AB  - The authors performed 2 experiments investigating the influence of the belief
      that a vehicle crashed on witnesses' estimates of the vehicle's speed. In
      Experiment 1, participants saw a video of a civilian car being driven, after
      which they were assigned to 1 of 2 conditions. The 1st group was told that the
      vehicle subsequently crashed; the 2nd group was not told that the vehicle
      crashed. The results indicted no differences between the 2 groups on a number of
      factors, including estimates of the vehicle's speed. Experiment 2 was identical
      except that the video showed a police car using flashing lights and sirens.
      Participants who had been told that the car had crashed overestimated speed, the
      likelihood of a crash, and the likelihood of someone being killed. Participants
      who were not told that the vehicle crashed estimated the speed of the vehicle
      accurately. Confidence in their estimates of speed was not significantly
      different between the 2 groups. Results are discussed with regard to police
      investigations of road accidents.

PMID- 12523449
TI  - Experiences of longing in Norwegian and Swedish 4- and 5-year-old children.
AB  - Longing can be defined as a blend of the primary emotions of happiness and
      sadness. These primary emotions are experienced very early by children, and the
      meanings of the words happiness and sadness are also known by children early in
      their verbal development. To find out at what age children are able to understand
      and use the more developed concept of longing, the authors interviewed 74
      preschoolers (4- and 5-year-olds) in Norway and Sweden about their experiences of
      longing. Chi-square analyses showed age and sex differences in knowledge of the
      concept, and some differences between categories of longing were also
      significant. Results showed that young children's ability to understand and use
      the concept of longing appears to be limited and that girls seem to mature
      earlier in this respect than boys do.

PMID- 12523450
TI  - Determinants of loneliness of young adult drug users.
AB  - Loneliness is a subjective experience that is influenced by such variables as
      personality, life experiences, and situation. In the present study, the author
      examined the connection between the use of ecstasy (MDMA) and the antecedents of
      loneliness. MDMA users were compared with non-MDMA drug users and with a group of
      young adults in the general population who did not use drugs. A total of 818
      participants from all 3 groups volunteered to answer a 30-item yes-no
      questionnaire reflecting on their experiences of loneliness and what caused them.
      Results showed that the predominant causes of loneliness were personal
      inadequacies, developmental deficits, unfulfilling intimate relationships,
      relocation or significant separations, and social marginality. There were
      significant differences between the scores of the MDMA users and scores of the
      other groups. Gender differences between and within groups were also examined.

PMID- 12523451
TI  - Dimensions of depression and perfectionism in pregnant and nonpregnant women:
      their levels and interrelationships and their relationship to marital
      satisfaction.
AB  - The authors studied S. J. Blatt's (1974) 2 dimensions of depression (anaclitic
      and introjective), P. L. Hewitt and G. L. Flett's (1991b) 3 dimensions of
      perfectionism (socially prescribed, self-oriented, and other-oriented), and the
      relationship between these and marital satisfaction in 100 married women in the
      last trimester of their first pregnancy and in 50 married women who had not yet
      experienced pregnancy. The measures used were the Depressive Experiences
      Questionnaire (S. J. Blatt, J. P. D'Afflitti, & D. M. Quinlan. 1976a, 1976b), the
      Multidimensional Perfectionism Scale (P. L. Hewitt & G. L. Flett, 1989), and G.
      B. Spanier's (1976) Dyadic Adjustment Scale. Pregnant and nonpregnant women did
      not differ in anaclitic depression, but the level of introjective depression of
      pregnant women was lower than that of nonpregnant women. The two groups did not
      differ in level of marital satisfaction or in any of the dimensions of
      perfectionism. For both groups, introjective depression was positively correlated
      with socially prescribed perfectionism and negatively correlated with marital
      satisfaction. Self-oriented perfectionism was positively related to introjective
      depression and negatively related to marital satisfaction for nonpregnant women.
      For the pregnant women, there was a negative relationship between socially
      prescribed perfectionism and marital satisfaction. Anaclitic depression and other
      oriented perfectionism were unrelated to any of the other variables studied.

PMID- 12523452
TI  - Turkish college students' attitudes toward women managers: the effects of
      patriarchy, sexism, and gender differences.
AB  - The authors examined how patriarchy, sexism, and gender influence Turkish college
      students' attitudes toward women managers. Turkish undergraduate students (N =
      183) from Middle East Technical University completed questionnaires measuring
      attitudes toward women managers as well as attitudes toward the concepts of
      hostile and benevolent sexism and support for patriarchy. Participants were of
      upper- or middle-class Turkish backgrounds. The results showed that male
      participants exhibited less positive attitudes toward women managers than did
      female participants. In addition, participants who held more favorable attitudes
      toward patriarchy and who scored high on hostile sexism also held less positive
      attitudes toward women managers than those who held less favorable attitudes
      toward patriarchy and who scored low on hostile sexism. A regression analysis
      showed that support for patriarchy and hostile sexism was more important for
      explaining less favorable attitudes toward women managers than was benevolent
      sexism.

PMID- 12523453
TI  - An investigation of worry and sense of humor.
AB  - To investigate the relationship between worry and sense of humor, the author
      administered the Worry Domains Questionnaire (WDQ; F. Tallis, M. Eysenck, & A.
      Matthews, 1992) and the Multidimensional Sense of Humor Scale (MSHS; J. A.
      Thorson & F. C. Powell, 1993) to 140 undergraduates. Worry was negatively related
      to sense of humor. Results of a stepwise regression, using the WDQ as the
      criterion and the MSHS factors as predictors, showed that the humor production
      factor of the MSHS loaded negatively on Step 1 and the coping with humor factor
      loaded positively on Step 2. The results are discussed in relation to W. E. Kelly
      and M. J. Miller's (1999) cognitive model of worry and worry as a coping
      strategy.

PMID- 12523454
TI  - Examining contrast effects in performance appraisals: using appropriate controls
      and assessing accuracy.
AB  - In research on contrast effects in performance appraisals, control conditions or
      measures of accuracy have rarely been used. In the present study, the authors
      included appropriate controls and used expert ratings to develop "true scores"
      for assessing accuracy. The study is an examination of the influence of 3
      variables on performance ratings: (a) the sequence of viewing and rating
      performance, (b) the delay between viewing and rating performance, and (c)
      whether the target of the performance rating was the same person as the anchor.
      Experimental conditions did not have the expected differential effects on target
      ratings, but target ratings in all the experimental conditions showed contrast
      effects when compared with ratings in relevant control conditions. The target
      ratings in experimental conditions were accurate, however, as assessed by
      comparisons with true scores, thus raising questions about the relationship
      between contrast effects and accuracy.

PMID- 12523455
TI  - Warfarin therapy and risk of hip fracture among elderly patients.
AB  - STUDY OBJECTIVE: To ascertain the relationship between warfarin therapy and
      subsequent hip fracture in a large elderly population. DESIGN: Retrospective,
      population-based cohort study. SETTING: Population-based health care
      administrative databases for Ontario, Canada. PATIENTS: Elderly patients
      receiving warfarin (52,701 patients), thyroid replacement therapy (40,555), an
      oral corticosteroid (43,915), or a proton pump inhibitor (60,383). The proton
      pump inhibitor group served as controls. MEASUREMENTS AND MAIN RESULTS: The
      association between warfarin therapy and subsequent hospitalization for hip
      fracture in elderly patients was examined by researching administrative data from
      January 1, 1994-March 31, 1999, for the elderly population of Ontario. Relative
      to patients receiving proton pump inhibitors, patients receiving warfarin
      (adjusted risk ratio [aRR] 0.94, 95% confidence interval [CI] 0.81-1.09) or
      thyroid replacement therapy (aRR 1.02, 95% Cl 0.89-1.18) incurred similar risks
      of hip fracture. As expected, patients receiving oral corticosteroids incurred an
      increased risk (aRR 1.44, 95% CI 1.21-1.70) relative to patients receiving proton
      pump inhibitors. CONCLUSION: Warfarin was not associated with increased risk of
      hip fracture.

PMID- 12523456
TI  - Erythromycin accelerates gastric emptying in a dose-response manner in healthy
      subjects.
AB  - STUDY OBJECTIVES: To evaluate whether a dose-response curve exists for
      erythromycin, determine the lowest effective dose of erythromycin needed to
      improve gastric motility, and compare erythromycin's effectiveness with that of
      metoclopramide in improving gastric emptying. DESIGN: Randomized, crossover,
      multiintervention trial. SETTING: Inpatient clinical research center. SUBJECTS:
      Ten healthy volunteers (four men, six women) from the general population.
      INTERVENTION: On each study day, the subjects were infused with erythromycin 0.75
      mg/kg, 1.5 mg/kg, or 3.0 mg/kg; metoclopramide 10 mg; or placebo, in random
      order. Subjects then drank Ensure 200 ml mixed with acetaminophen 1.5 g. Gastric
      emptying was estimated by comparing the area under the curve after 60 minutes for
      acetaminophen absorption using four timed blood draws. MEASUREMENTS AND MAIN
      RESULTS: Erythromycin increased gastric emptying in a dose-response manner.
      Erythromycin 3.0 mg/kg and metoclopramide 10 mg were associated with
      statistically significant increases in liquid gastric emptying compared with
      placebo. During infusion, nausea and stomach cramping were associated with the
      3.0-mg/kg dose of erythromycin; drowsiness was associated with metoclopramide.
      CONCLUSION: In patients requiring intravenous erythromycin for gastric motility,
      the 3.0-mg/kg dose seems the most effective, with a reasonable side effect
      profile.

PMID- 12523457
TI  - Selective cyclooxygenase-2 inhibition: a target in cancer prevention and
      treatment.
AB  - A major goal in the area of cancer prevention and treatment is to make rational
      use of defined molecular targets in order to block carcinogenesis. Studies
      conducted in experimental animal models for many human cancers, including those
      of lung, skin, mammary gland, urinary bladder, colon, and pancreas, have
      demonstrated that carcinogenesis often may be inhibited by the administration of
      a highly diverse group of biologic and chemical agents. One very promising and
      well-studied target is cyclooxygenase (COX)-2. Interestingly, a number of cancers
      appear to overexpress the COX-2 enzyme, which may play several roles in
      carcinogenesis. Recent clinical studies have demonstrated the effect of COX-2
      inhibitors in the treatment of familial adenomatous polyposis, a genetic disorder
      that increases the risk for developing colorectal cancer. Ongoing clinical trials
      with COX-2 inhibitors will increase our understanding and may give us profound
      insights into the general applicability of this new targeted approach for cancer
      control.

PMID- 12523458
TI  - Tenofovir: a nucleotide analog for the management of human immunodeficiency virus
      infection.
AB  - Tenofovir disoproxil fumarate, an acyclic nucleotide analog of adenosine
      monophosphate, is the most recent addition to the antiretroviral arsenal. After
      conversion to tenofovir by diester hydrolysis, subsequent phosphorylation by
      cellular enzymes to form the active tenofovir diphosphate is necessary for
      antiretroviral activity. Preliminary data suggest that tenofovir is as safe and
      efficacious as stavudine when given in combination with lamivudine and efavirenz
      for the treatment of antiretroviral-naive patients. In antiretroviral-experienced
      patients, the addition of tenofovir to stable background antiretroviral therapy
      resulted in approximately a 0.6 log10 copies/ml reduction in viral load relative
      to placebo. Extended follow-up suggests that such virologic gains may be durable.
      In vitro, recombinant human immunodeficiency virus (HIV) expressing the K65R
      mutation showed a 3-4-fold increase in the 50% inhibitory concentrations of
      tenofovir when compared with wild type. In vivo, this mutation thus far appears
      to occur infrequently and is associated with variable virologic responses.
      Response rates to tenofovir vary with the number and pattern of thymidine analog
      mutations present before starting treatment with this agent. Tenofovir appears to
      be a well-tolerated agent in patients who are heavily pretreated and who have
      advanced disease. The main adverse effects appear to be gastrointestinal in
      nature and include nausea, vomiting, and diarrhea. In animals, osteomalacia and
      nephrotoxicity have occurred with tenofovir at exposures much higher than those
      observed in humans. Although no patient had to discontinue therapy as a result of
      elevated creatinine levels or hypophosphatemia through 58 weeks of treatment, the
      toxicities associated with long-term tenofovir therapy in humans are unknown.
      Concomitant administration of tenofovir and didanosine increases the area under
      the concentration-time curve of the latter by 44-60%; monitoring for signs and
      symptoms of didanosine toxicity is recommended. The approved dosage of tenofovir
      is 300 mg (one tablet) once/day with meals. Given the ease of administration and
      relative safety from the perspectives of adverse effects and drug interactions,
      tenofovir has the potential to assume a large role in the treatment of patients
      with HIV infection.

PMID- 12523459
TI  - Clinical issues surrounding once-daily aminoglycoside dosing in children.
AB  - Aminoglycoside antibiotics are first-line treatment for many infectious diseases
      in the pediatric population and are effective in adults. The traditional dosing
      interval in children is every 8-12 hours. Studies in adults reported equivalent
      efficacy and equal or less toxicity with once-daily regimens. Despite many
      studies in the adult population, this approach has yet to become standard
      practice in most pediatric hospitals. Reasons for lack of acceptance of this
      strategy in children include rapid aminoglycoside clearance, unknown duration of
      postantibiotic effect, safety concerns, and limited clinical and efficacy data.

PMID- 12523460
TI  - Low-molecular-weight heparin in transesophageal echocardiography-guided
      cardioversion of atrial fibrillation.
AB  - Atrial fibrillation is the most common sustained cardiac arrhythmia and is
      associated with thromboembolic events and hemodynamic impairment that results in
      considerable morbidity, mortality, and cost. Cardioversion to sinus rhythm is a
      common approach to the treatment of these patients. However, cardioversion is
      associated with the risk of thromboembolism. Current guidelines recommend that
      patients receive anticoagulants for 3-4 weeks before and 4 weeks after
      cardioversion. With the development of transesophageal echocardiography (TEE),
      the risk of thromboembolism and alternative anticoagulation strategies have been
      evaluated in patients with atrial fibrillation. Administration of low-molecular
      weight heparin (LMWH) in conjunction with TEE offers several advantages over
      unfractionated heparin. Limited data suggest that LMWH in this setting is as
      effective, is safer, and may be more cost-effective than unfractionated heparin.
      Ongoing research will identify definitively the optimal strategy for
      pericardioversion anticoagulation.

PMID- 12523461
TI  - Clinic at the health food store? Employee recommendations and product analysis.
AB  - STUDY OBJECTIVES: To determine what products health food store employees
      recommend for depression, to analyze the content of these products based on label
      claims, and to evaluate employee statements or recommendations for accuracy and
      safety. METHODS: Twelve health food stores were selected for the study. One
      investigator approached an employee in each store and asked what they recommended
      for depression plus five additional questions regarding product use. Thirteen
      products containing St. John's wort were purchased and analyzed for hypericin and
      pseudohypericin content using high-performance liquid chromatography (HPLC).
      Total hypericin content was calculated by adding the values for hypericin and
      pseudohypericin. RESULTS: All 12 health food store employees recommended a St.
      John's wort supplement for treatment of depression. Furthermore, numerous
      comments made by employees regarding St. John's wort and the treatment of
      depression were unsafe and inaccurate. The HPLC analysis revealed that no product
      contained +/- 10% of the stated label claim for hypericin content, and two
      products contained 0% hypericin. The total hypericin content (hypericin plus
      pseudohypericin) of only two products was within +/- 10% of the label claim for
      hypericin. CONCLUSIONS: Health food store employees offer health care advice
      regarding treatment of depression with dietary supplements without proper
      scientific and medical training. Their comments could cause significant harm to
      customers. In addition, the inconsistencies of dietary supplement content
      continue to raise concern for individuals who use these agents as medical
      treatment.

PMID- 12523462
TI  - Improving aspirin prophylaxis in a primary care diabetic population.
AB  - STUDY OBJECTIVE: To evaluate and improve adherence to American Diabetes
      Association guidelines for prophylactic aspirin therapy in ambulatory patients
      with diabetes using a pharmacy-directed intervention. DESIGN: Unblinded, single
      intervention. SETTING: Rural, primary care clinic. SUBJECTS: Eighty-five patients
      with a diagnosis of diabetes mellitus. INTERVENTION: Patients with diabetes were
      identified from database searches and routine clinic visits. Medical records were
      screened for aspirin use, allergies, adverse events, and contraindications.
      During routine clinic visits or structured telephone interviews, patients with
      indications for aspirin therapy were advised to begin enteric-coated aspirin 81
      mg/day A follow-up survey assessed adherence. MEASUREMENTS AND MAIN RESULTS: At
      baseline, 28 (33%) of 85 patients were receiving aspirin therapy An additional 8
      patients had contraindications to aspirin, and 2 patients had no indications for
      aspirin therapy Aspirin was recommended to 27 patients during clinic
      interventions and to 15 patients during telephone interventions. Two patients
      declined the recommendation. At the completion of this intervention, 70 (82%) of
      85 patients were receiving daily aspirin or had accepted the recommendation to
      begin therapy. CONCLUSIONS: A pharmacy-directed intervention increased
      prophylactic aspirin therapy in patients with diabetes from 33% of patients at
      baseline to 82% at the end of the study The intervention, which has a simple,
      patient-focused design, serves as a template for improving aspirin prophylaxis
      among patients with diabetes in other ambulatory settings.

PMID- 12523463
TI  - Meta-analysis of interventions to improve drug adherence in patients with
      hyperlipidemia.
AB  - OBJECTIVE: To examine the results of meta-analyses addressing the net effect of
      tools and methods to enhance drug adherence in patients with hyperlipidemia.
      METHODS: We searched MEDLINE, International Pharmaceutical Abstracts (IPA),
      PsychLit, Educational Resource Information Clearinghouse (ERIC), and Excerpta
      Medica Database (EMBASE) databases (1996-2000) for randomized controlled trials
      of interventions to improve patients' adherence to drug regimens for
      hyperlipidemia. All trials selected had at least 10 subjects/group. Effect sizes,
      represented as the correlation coefficient, were calculated from Cohen's d and
      d'. Analysis of variance and the Q test were performed to evaluate statistical
      significance and heterogeneity. RESULTS: Of the 484 articles evaluated, only four
      met the criteria for inclusion. Multiple interventions or study samples were
      identified in two articles. Each intervention was counted as a separate study,
      yielding seven cohorts with a total of 3077 subjects. Behavioral interventions
      accounted for five cohorts (2915 subjects). No cohorts received solely
      educational interventions. Two cohorts, with a total of 162 subjects, received a
      combination of behavioral and educational interventions. Homogeneity of groupings
      and effect sizes were calculated for the overall grouping as well as for each
      type of intervention. Overall, the effect size for the data was 0.14 (95%
      confidence interval [CI] 0.10-0.17) and the data were homogenous (Q = 7.36, df =
      4, p = 0.29). The effect size for the behavioral interventions was 0.14 (95% CI
      0.11-0.18, Q = 5.25, df = 4, p = 0.26). For interventions that combined
      behavioral and educational components, the effect size was 0.03 (CI -0.13-0.18, Q
      = 0.204, df = 1, p = 0.65). CONCLUSIONS: The interventions evaluated had little
      impact on drug adherence. More studies are needed to assess how to improve drug
      adherence in patients with hyperlipidemia.

PMID- 12523464
TI  - Albumin use in neurosurgical critical care.
AB  - STUDY OBJECTIVE: To examine the use of albumin in patients receiving
      neurosurgical intensive care. DESIGN: Survey and chart review of albumin use in
      neurosurgical intensive care units. SETTING: University of Kentucky Chandler
      Medical Center and American Brain Injury Consortium (ABIC). SUBJECTS: Thirty
      eight patients who underwent neurosurgery at the University of Kentucky Chandler
      Medical Center; members of the ABIC. INTERVENTIONS: Chart review with attention
      to administration of albumin; mailed survey to 200 ABIC members. MEASUREMENTS AND
      MAIN RESULTS: Patients admitted to the neurosurgical intensive care unit at the
      University of Kentucky Chandler Medical Center over a 6-month interval were
      evaluated. Albumin, either 5% or 25%, was prescribed for approximately 25% of
      patients. The indications for use were vasospasm and maintenance of cerebral
      perfusion pressure. The response rate for the ABIC survey was 39%. Respondents
      stated that normal saline and albumin were both primary fluid choices for the
      treatment of vasospasm. Twenty-two percent reported a reduction in albumin
      prescribing following a formal warning statement issued by the Food and Drug
      Administration regarding the use of albumin in critically ill patients.
      CONCLUSIONS: Chart review revealed the primary indications for albumin in the
      neurosurgical intensive care unit, and our survey data demonstrated the lack of
      consensus among neurosurgeons regarding their fluid of choice for neurosurgery
      indications. Prospective, randomized investigations comparing colloids to
      crystalloids in patients receiving neurosurgical intensive care are required to
      help define the role of albumin in neurosurgery patients.

PMID- 12523465
TI  - Visual hallucinations associated with zonisamide.
AB  - Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of
      seizures. Although visual hallucinations have not been reported as an adverse
      effect of this agent, we describe three patients who experienced complex visual
      hallucinations and altered mental status after zonisamide treatment was begun or
      its dosage increased. All three had been diagnosed earlier with epilepsy, and
      their electroencephalogram (EEG) findings were abnormal. During monitoring,
      visual hallucinations did not correlate with EEG readings, nor did video
      recording capture any of the described events. None of the patients had
      experienced visual hallucinations before this event. The only recent change in
      their treatment was the introduction or increased dosage of zonisamide. With
      either discontinuation or decreased dosage of the drug the symptoms disappeared
      and did not recur. Further observations and reports will help clarify this
      adverse effect. Until then, clinicians need to be aware of this possible
      complication associated with zonisamide.

PMID- 12523466
TI  - Celecoxib in human milk: a case report.
AB  - Many women of reproductive age take the nonsteroidal antiinflammatory drug
      celecoxib. No data exist, however, regarding its transfer into human breast milk
      and safety for breastfed infants. We had the opportunity to obtain such data when
      a woman who was breastfeeding her infant daughter underwent emergency surgery to
      remove a gangrenous appendix. She received four doses of oral celecoxib 100 mg
      and did not breastfeed her daughter for 48 hours after taking the last dose. We
      analyzed samples of her breast milk and found a concentration of 133 ng/ml at
      approximately 5 hours after a 100-mg dose and an elimination half-life of 4.0-6.5
      hours. This initial report, which should be substantiated and expanded, provides
      information that can help counsel parents about breastfeeding and celecoxib.

PMID- 12523467
TI  - Neutropenia after single-dose clindamycin for dental prophylaxis.
AB  - A 68-year-old man with stable chronic myelogenous leukemia received a single dose
      of clindamycin before having a tooth extracted. He was neutropenic 6 days later,
      with an absolute neutrophil count of 945 cells/mm3. His neutrophil count returned
      to normal within 2 weeks. Clindamycin has been implicated in drug-induced
      neutropenia; however, a review of the literature produced only three reports of
      this reaction. Only one provided the duration of the neutropenia. To our
      knowledge, this case report is only the second that provides the duration of the
      clindamycin-induced neutropenia. Clinicians should be made aware of this
      potential adverse event.

PMID- 12523468
TI  - Recurring chemotherapy-associated alopecia areata: case report and literature
      review.
AB  - A 52-year-old woman with stage IIIC ovarian cancer and stage IA uterine cancer
      experienced recurring alopecia areata of her eyebrows, eyelashes, arms, legs, and
      pubic area beginning 5 months after completing chemotherapy with paclitaxel and
      carboplatin. The condition recurred in a cyclic fashion over the ensuing months.
      Alopecia is a well-recognized adverse event associated with chemotherapy;
      however, to our knowledge, this cyclic pattern of alopecia has not been reported
      in a patient with cancer. Our report of a cancer survivor who experienced cyclic
      alopecia areata indicates that this condition may be related to autoimmune
      changes instigated by chemotherapy. Oncology health care practitioners should
      evaluate unusual clinical cases of alopecia for underlying pathology.

PMID- 12523469
TI  - Warfarin and acetaminophen interaction.
AB  - A 74-year-old man who was receiving warfarin for atrial fibrillation experienced
      an abrupt increase in his international normalized ratio (INR) after taking
      acetaminophen. To investigate this effect, the patient's anticoagulation therapy
      was stabilized, and he was given acetaminophen 1 g 4 times/day for 3 days. His
      INR rose from 2.3 before receiving acetaminophen to 6.4 on the day after
      acetaminophen was discontinued. Warfarin was stopped for 2 days, and the
      patient's INR returned to 2.0. Warfarin was restarted at the same dosage, and his
      INR remained within 2.0-3.0 for 6 months. Factor VII activity decreased from
      29.4% before acetaminophen therapy to 15.5% when his INR was 6.4, and factor X
      activity fell from 27.0% to 20.2%. His warfarin plasma concentration was 1.54
      microg/ml before acetaminophen compared with 1.34 microg/ml when his INR was 6.4.
      No significant changes in drug intake, clinical status, diet, or lifestyle were
      noted. Changes in INR of this magnitude with the addition of another drug during
      stable anticoagulation therapy suggest a drug interaction. The lack of an
      increase in warfarin plasma concentration associated with the increased INR
      suggests a possible pharmacodynamic mechanism for this interaction. Acetaminophen
      or a metabolite may enhance the effect of oral coumarin anticoagulants by
      augmenting vitamin K antagonism. Thus, the anticoagulant effect of warfarin may
      be significantly elevated after only a few days of acetaminophen therapy.
      Patients receiving warfarin should be counseled to have their INR monitored more
      frequently when starting acetaminophen at dosages exceeding 2 g/day.

PMID- 12523470
TI  - Evidence of the economic benefit of clinical pharmacy services: 1996-2000.
AB  - We sought to summarize and assess original evaluations of the economic impact of
      clinical pharmacy services published from 1996-2000, and to provide
      recommendations and methodologic considerations for future research. A systematic
      literature search was conducted to identify articles that were then blinded and
      randomly assigned to reviewers who confirmed inclusion and abstracted key
      information. Results were compared with those of a similar review of literature
      published from 1988-1995. In the 59 included articles, the studies were conducted
      across a variety of practice sites that consisted of hospitals (52%), community
      pharmacies and clinics (41%), health maintenance organizations (3%), and long
      term or intermediate care facilities (3%). They focused on a broad range of
      clinical pharmacy services such as general pharmacotherapeutic monitoring (47%),
      target drug programs (20%), disease management programs (10%), and patient
      education or cognitive services (10%). Compared with the studies of the previous
      review, a greater proportion of evaluations were conducted in community
      pharmacies or clinics, and the types of services evaluated tended to be more
      comprehensive rather than specialized. Articles were categorized by type of
      evaluation: 36% were considered outcome analyses, 24% full economic analyses, 17%
      outcome descriptions, 15% cost and outcome descriptions, and 8% cost analyses.
      Compared with the studies of the previous review, a greater proportion of studies
      in the current review used more rigorous study designs. Most studies reported
      positive financial benefits of the clinical pharmacy service evaluated. In 16
      studies, a benefit:cost ratio was reported by the authors or was able to be
      calculated by the reviewers (these ranged from 1.7:1-17.0:1, median 4.68:1). The
      body of literature from this 5-year period provides continued evidence of the
      economic benefit of clinical pharmacy services. Although the quality of study
      design has improved, whenever possible, future evaluations of this type should
      incorporate methodologies that will further enhance the strength of evidence of
      this literature and the conclusions that may be drawn from it.

PMID- 12523471
TI  - Veterinary participation in emergency response plans is vital.

PMID- 12523472
TI  - Minnesota director clarifies avian influenza inaccuracies.

PMID- 12523473
TI  - Shelters concerned about screening for FIV.

PMID- 12523474
TI  - The lack of racial diversity in veterinary medicine.

PMID- 12523475
TI  - What is your diagnosis? Diffuse nodular bronchointerstitial pattern.

PMID- 12523476
TI  - Practicing veterinary medicine across state lines--are you legal?

PMID- 12523477
TI  - Evaluation of the sedative and cardiorespiratory effects of dexmedetomidine,
      dexmedetomidine-butorphanol, and dexmedetomidine-ketamine in cats.
AB  - OBJECTIVE: To determine sedative and cardiorespiratory effects of dexmedetomidine
      alone and in combination with butorphanol or ketamine in cats. DESIGN: Randomized
      crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given
      dexmedetomidine alone (10 microg/kg [4.5 mg/lb], IM), a combination of
      dexmedetomidine (10 microg/kg, IM) and butorphanol (0.2 mg/kg [0.09 mg/lb], IM),
      or a combination of dexmedetomidine (10 microg/kg, IM) and ketamine (5 mg/kg [2.3
      mg/lb], IM). Treatments were administered in random order, with > or = 1 week
      between treatments. Physiologic variables were assessed before and after drug
      administration. Time to lateral recumbency, duration of lateral recumbency, time
      to sternal recumbency, time to recovery from sedation, and subjective evaluation
      of sedation, muscle relaxation, and auditory response were assessed. RESULTS:
      Each treatment resulted in adequate sedation; time to lateral recumbency,
      duration of lateral recumbency, and time to recovery from sedation were similar
      among treatments. Time to sternal recumbency was significantly greater after
      administration of dexmedetomidine-ketamine. Heart rate decreased significantly
      after each treatment; however, the decrease was more pronounced after
      administration of dexmedetomidine-butorphanol, compared with that following the
      other treatments. Systolic and diastolic blood pressure measurements decreased
      significantly from baseline with all treatments; 50 minutes after drug
      administration, mean blood pressure differed significantly from baseline only
      when cats received dexmedetomidine and butorphanol. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that in cats, administration of dexmedetomidine
      combined with butorphanol or ketamine resulted in more adequate sedation, without
      clinically important cardiovascular effects, than was achieved with
      dexmedetomidine alone.

PMID- 12523478
TI  - Evaluation of the effect of a long-term trap-neuter-return and adoption program
      on a free-roaming cat population.
AB  - OBJECTIVE: To evaluate the effect of a long-term trap-neuter-return program, with
      adoption whenever possible, on the dynamics of a free-roaming cat population.
      DESIGN: Observational epidemiologic study. ANIMALS: 155 unowned free-roaming
      cats. PROCEDURES: Free-roaming cats residing on a university campus were trapped,
      neutered, and returned to the environment or adopted over an 11-year period.
      RESULTS: During the observation period (January 1991 to April 2002), 75% of the
      cats were feral, and 25% were socialized. Kittens comprised 56% of the original
      population. Male cats were slightly more numerous (55%) than females. At the
      conclusion of the observation period, 47% of the cats had been removed for
      adoption, 15% remained on site, 15% had disappeared, 11% were euthanatized, 6%
      had died, and 6% had moved to the surrounding wooded environment. Trapping began
      in 1991; however, a complete census of cats was not completed until 1996, at
      which time 68 cats resided on site. At completion of the study in 2002, the
      population had decreased by 66%, from 68 to 23 cats (of which 22 were feral). No
      kittens were observed on site after 1995, but additional stray or abandoned cats
      continued to become resident. New arrivals were neutered or adopted before they
      could reproduce. CONCLUSIONS AND CLINICAL RELEVANCE: A comprehensive long-term
      program of neutering followed by adoption or return to the resident colony can
      result in reduction of free-roaming cat populations in urban areas.

PMID- 12523479
TI  - Detection of Bartonella henselae and Bartonella clarridgeiae DNA in hepatic
      specimens from two dogs with hepatic disease.
AB  - A 4-year-old Basset Hound and a 6-year-old Doberman Pinscher were referred for
      diagnostic evaluation following documentation of persistently increased hepatic
      enzyme activities and hepatic dysfunction. Histologic evaluation of hepatic
      biopsy specimens from the 2 dogs revealed granulomatous hepatitis in the Basset
      Hound and lymphocytic hepatitis with fibrosis and copper accumulation in the
      Doberman Pinscher. No etiologic agents were identified histologically. Bartonella
      henselae DNA was subsequently amplified from hepatic tissue from the Basset Hound
      and Bartonella clarridgeiae was amplified from hepatic tissue from the Doberman
      Pinscher. Amplification was performed with a polymerase chain reaction assay
      incorporating primers that target a portion of the 16S-23S rRNA intergenic spacer
      region. Both dogs were treated with azithromycin, in combination with a variety
      of other medications and herbal treatments, and improved clinically.
      Identification of Bartonella DNA in these dogs indicates the need for future
      prospective studies to determine the clinical relevance of Bartonella spp
      infection in dogs with hepatic disease.

PMID- 12523480
TI  - Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs.
AB  - In this report, we describe the natural intoxication of 2 dogs that consumed
      moldy dairy products found in the household garbage and the procedures used to
      identify and quantify the tremorgenic mycotoxins, roquefortine and penitrem A, in
      the remaining portions of ingested materials. Following the ingestion of
      mycotoxins, the dogs of our report developed muscle tremors or seizures that
      resembled clinical signs of strychnine poisoning. Roquefortine was the
      predominant mycotoxin in a moldy cream cheese wrapper that was found among
      scattered garbage consumed by the first dog. Penitrem A was the only mycotoxin
      detected in discarded moldy macaroni and cheese that was consumed by the second
      dog. Treatment of dogs with tremorgenic mycotoxin intoxication involves
      supportive care. Close monitoring is important because the development of
      aspiration pneumonia is common and has been reported as the cause of death.
      Clinical signs of intoxication gradually resolve within 24 to 48 hours.

PMID- 12523482
TI  - Pregnancies attained after collection and transfer of oocytes from ovaries of
      five euthanatized mares.
AB  - After euthanasia, ovaries were removed from 5 horses and shipped to a laboratory
      where 46 oocytes were collected. The oocytes were cultured for 24 to 30 hours,
      and 36 oocytes were transferred to 10 recipient mares via flank laparotomies.
      Recipient mares were inseminated with semen from various stallions. Sixteen days
      after transfer, 4 of the recipients were pregnant with at least 1 embryonic
      vesicle. Embryonic death occurred in 3 recipients, whereas a healthy live foal
      was born from 1 recipient. Ovaries from valuable mares can be a source of viable
      oocytes after death of the mare. For shipping to a laboratory, fluctuations in
      temperature should be minimized and the ovaries should not be chilled.

PMID- 12523481
TI  - Results of single-session bilateral triple pelvic osteotomy with an eight-hole
      iliac bone plate in dogs: 95 cases (1996-1999).
AB  - OBJECTIVE: To evaluate feasibility of single-session bilateral triple pelvic
      osteotomy with 8-hole iliac bone plates in dogs with bilateral hip dysplasia.
      DESIGN: Retrospective study. ANIMALS: 95 dogs with bilateral hip dysplasia.
      PROCEDURE: Medical records were reviewed, and information was obtained on
      signalment; body weight; angles of subluxation and reduction prior to surgery;
      durations of surgery and hospitalization; postoperative mobility; severity of
      lameness, radiographic grade of hip dysplasia, Norberg angle, and femoral head
      coverage before and after surgery; time required for radiographic evidence of
      iliac healing; change in pelvic diameter; implant integrity; and complications.
      RESULTS: Mean age at the time of surgery was 10.8 months, and mean weight was
      35.2 kg (77.4 lb). Prior to surgery, mean angles of subluxation were 2.2 degrees
      on the right and 2.6 degrees on the left; mean angles of reduction were 25.9
      degrees on the right and 27.3 degrees on the left. Mean surgical time was 95
      minutes. All but 1 dog were able to walk on their own by the fourth day after
      surgery. Mean hospitalization time was 7.5 days. Clinical signs of lameness and
      radiographic grade of hip dysplasia were significantly improved during follow-up
      examinations. Mean time for radiographic iliac healing was 8 weeks. None of the
      plates and only 7 of the 1,520 (0.5%) screws loosened after surgery. Nineteen
      dogs had complications, but all complications were minor. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that single-session bilateral triple pelvic
      osteotomy with 8-hole iliac bone plates is effective for treatment of dogs with
      bilateral hip dysplasia.

PMID- 12523483
TI  - Evaluation of frequent milkout for treatment of cows with experimentally induced
      Escherichia coil mastitis.
AB  - OBJECTIVE: To evaluate the effect of frequent milkout (FMO) on the outcome of
      experimentally induced Escherichia coli mastitis in cows. DESIGN: Randomized
      complete block study. ANIMALS: 16 Holstein dairy cows. PROCEDURE: Cows were
      randomly assigned to 1 of 4 groups and were either not infected and not treated
      (NI-NT), experimentally infected with E coli and not treated (EC-NT), not
      infected and FMO (NI-FMO), or experimentally infected with E coli and FMO (EC
      FMO). The infected quarter in cows in FMO groups was milked out every 4 hours
      from 16 to 36 hours and every 6 hours from 36 to 84 hours after challenge, with
      the aid of oxytocin administration. Somatic cell counts (SCC); times to
      bacterial, clinical, and systemic cures; and serum concentrations of a
      lactalbumin were determined. RESULTS: Use of FMO did not appear to affect SCC.
      For EC-NT and EC-FMO groups, mean bacterial cure times were 203 and 159 hours,
      clinical cure times were 276 and 360 hours, and systemic cure times were 144 and
      159 hours, respectively; these times were not significantly different.
      Concentrations of a-lactalbumin were significantly increased in the EC-NT group
      at 12 hours and in the NI-FMO group at 36 and 60 hours after challenge, compared
      with values of cows in other treatment groups. CONCLUSIONS AND CLINICAL
      RELEVANCE: Compared with results in control cows, FMO does not appear to be an
      efficacious treatment for experimentally induced moderate to severe E coli
      mastitis.

PMID- 12523484
TI  - Neuronal basis of neuroleptic-induced extrapyramidal side effects.
AB  - The article reviews presently commonly accepted concepts of neuronal basis of
      neuroleptic-induced extrapyramidal side effects. The data obtained both, in
      humans and laboratory animals, point to the blockade of a large number of the
      striatal dopamine D2 receptors by neuroleptics as a primary cause of these
      disturbances. This phenomenon leads to the appearance of parkinsonian symptoms
      shortly after therapy commencement. On the other hand, chronic administration of
      neuroleptics evokes supersensitivity to dopamine connected with the increased
      number of D2 receptors and supersensitivity of D1 receptors, which can be
      significant for the development of tardive dyskinesia. Primary and secondary
      changes in the function of dopamine receptors lead to partially opposite,
      pathological changes in the activity of neuronal pathways connecting the basal
      ganglia. Besides functional changes, neuroleptic-induced lesions of the striatal
      neurons and genetic predispositions can also play a role in tardive dyskinesia.

PMID- 12523485
TI  - Neuroprotective role of adenosine in the CNS.
AB  - It is well established that in the CNS, endogenous adenosine plays a pivotal role
      in neurodegeneration. A low, nanomolar concentration of adenosine is normally
      present in the extracellular fluid, but it increases dramatically during enhanced
      nerve activity, hypoxia or ischemia. In these pathological conditions,
      adenosinergic transmission-potentiating agents, which elevate adenosine level by
      either inhibiting its degradation (adenosine deaminase and kinase inhibitors) or
      preventing its transport, offer protection against ischemic or excitotoxic
      neuronal damage. The directly acting adenosine A1 receptor agonists are known to
      mediate neuroprotection, mostly by the blockade of Ca2+ influx, which results in
      the inhibition of glutamate release and reduction of its excitatory effects at a
      postsynaptic level. More recent data have shown that antagonists of adenosine A2A
      receptors markedly reduce cerebral ischemic damage in animal models of focal and
      global ischemia. Moreover, these compounds attenuate the neuronal loss induced by
      excitatory amino acids (EAA). A neuroprotective effect of adenosine A2A receptor
      antagonists was also shown in animal models of Parkinson's disease (MPTP, 6-OHDA,
      methamphetamine). Hence, it might be suggested that adenosine A2A receptor
      antagonists may represent a novel strategy in the therapeutic approach to
      pathologies characterized by acute or chronic neurodegenerative events, since
      they not only reverse motor impairment but can act as neuroprotective compunds by
      promoting cell survival.

PMID- 12523486
TI  - In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin
      receptors.
AB  - In recent years much attention has been focused on the functional importance of 5
      HT5, 5-HT6 and 5-HT7 receptors in the pathogenesis of neuropsychiatric and other
      diseases. In this connection, intensive studies with ligands of these receptors
      are currently in progress. Recognition of the structural characteristics
      responsible for the binding of a ligand molecule to an appropriate receptor, and
      development of an active complex have reached an advanced stage in the search for
      selective compounds. This review was undertaken to summarize the results of
      structure-activity relationship studies with ligands of 5-HT5, 5-HT6 and 5-HT7
      receptors. Additionally, some data on localization, pharmacological properties
      and the functional role of those receptors were reported.

PMID- 12523487
TI  - Effect of antidepressant drugs on the hypothalamic-pituitary-adrenal axis
      activity and glucocorticoid receptor function.
AB  - Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is the main
      biochemical change, besides disturbed monoaminergic neurotransmission, observed
      in the patients suffering from a major depression. High incidence of depression
      in Cushing's syndrome as well as antidepressant effects of adrenocortical enzyme
      inhibitors in major depression support hypothesis that hyperactivity of HPA axis
      may be involved in pathogenesis of depression.

PMID- 12523488
TI  - Effect of intra-tegmental microinjections of 5-HT1B receptor ligands on the
      amphetamine-induced locomotor hyperactivity in rats.
AB  - Previous research demonstrated that the mesoaccumbens dopamine (DA) pathway
      played a critical role in the behavioral effects of amphetamine in rodents.
      Nonetheless, recent findings have also indicated involvement of 5
      hydroxytryptamine (5-HT, serotonin) transmission in these effects. In the present
      study, we investigated the role of 5-HT1B receptors located in the ventral
      tegmental area (VTA) in the amphetamine-induced locomotor hyperactivity in rats.
      Male Wistar rats, implanted bilaterally with cannulae in the VTA were infused
      with saline (0.2 microl/side), GR 55562 (an antagonist of 5-HT1B receptors; 0.1-1
      microg/side) or CP 93129 (an agonist of 5-HT1B receptors; 0.003-0.03 microg/side)
      immediately prior to the injection of saline (1 ml/kg, ip) or amphetamine (0.5
      mg/kg, ip). The monitoring of locomotor activity in photobeam chambers began at
      once and proceeded for 60 min. Neither GR 55562 nor CP 93129 affected basal
      locomotor activity. Pretreatment with GR 55562 (0.1-1 microg/side) did not affect
      the locomotor hyperactivity evoked by amphetamine. On the other hand,
      microinjections of CP 93129 (0.01-0.03 microg/side) enhanced the amphetamine
      induced hyperlocomotor activity. GR 55562 (1 microg/side) markedly reduced the
      enhancing effects of CP 93129 (0.01 microg/side) on the amphetamine-induced
      hyperactivity. These findings indicate that 5-HT1B receptors located in the VTA
      do not play a major role in the hyperlocomotion elicited by amphetamine, whereas
      their activation may modulate the behavioral response to the psychostimulant.

PMID- 12523489
TI  - Cocaine-induced hyperactivity is more influenced by adenosine receptor agonists
      than amphetamine-induced hyperactivity.
AB  - The influence of adenosine receptor agonists and antagonists on cocaine-and
      amphetamine-induced hyperactivity was examined in mice. All adenosine receptor
      agonists significantly decreased the locomotor activity in mice, and the effects
      were dose-dependent. It seems that adenosine A1 and A2 receptors might be
      involved in this reaction. Moreover, all adenosine receptor agonists: 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), A2A
      receptor agonist, N6-cyclopentyladenosine (CPA), A1 receptor agonist, and 5'-N
      ethylcarboxamidoadenosine (NECA), A2/A1 receptor agonist significantly and dose
      dependently decreased cocaine-induced locomotor activity. CPA reduced cocaine
      action at the doses which, given alone, did not influence motility, while CGS
      21680 and NECA decreased the action of cocaine at the doses which, given alone,
      decreased locomotor activity in animals. These results suggest the involvement of
      both adenosine receptors in the action of cocaine although agonists of A1
      receptors seem to have stronger influence on it. The selective blockade of A2
      adenosine receptor by DMPX (3,7-dimethyl-1-propargylxanthine) significantly
      enhanced cocaine-induced locomotor activity of animals. Caffeine had similar
      action but the effect was not significant. CPT (8-cyclopentyltheophylline)--A1
      receptor antagonist, did not show any influence in this test. Similarly, all
      adenosine receptor agonists decreased amphetamine-induced hyperactivity, but at
      the higher doses than those which were active in cocaine-induced hyperactivity.
      The selective blockade of A2 adenosine receptors (DMPX) and non-selective
      blockade of adenosine receptors (caffeine) significantly increased the action of
      amphetamine in the locomotor activity test. Our results have shown that all
      adenosine receptor agonists (A1 and A2) reduce cocaine- and amphetamine-induced
      locomotor activity and indicate that cocaine-induced hyperactivity is more
      influenced by adenosine receptor agonists (particularly A1 receptors) than
      amphetamine-induced hyperactivity.

PMID- 12523490
TI  - Effect of cocaine and amphetamine on biosynthesis of proenkephalin and
      prodynorphin in some regions of the rat limbic system.
AB  - A vast body of evidence points to the role of the limbic system in the mechanism
      of drug dependence. Opioid peptides localized in the limbic system may play a
      role in central effects of substances of abuse. The goal of the present study was
      to investigate the influence of acutely and chronically administered drugs of
      abuse, cocaine and amphetamine on biosynthesis of prodynorphin and proenkephalin
      in the rat amygdala, the structure involved in the mechanism of drug addiction.
      Acute injection of cocaine (20 mg/kg ip every hour for 3 h) or amphetamine (2.5
      mg/kg) did not changed or decreased the level of proenkephalin mRNA in the
      central nucleus of the amygdala. In contrast, the level of prodynorphin mRNA was
      significantly increased in this structure after cocaine. Repeated cocaine
      administration (20 mg/kg ip every hour for 3 h, for 5 days) had no effect on the
      proenkephalin and prodynorphin mRNA in the central nucleus of the amygdala.
      Chronic amphetamine (2.5 mg/kg twice daily for 5 days) administration decreased
      proenkephalin and increased prodynorphin mRNA level in the central nucleus of the
      amygdala (at 24 and 48 h). Moreover, significant increase in prodynorphin mRNA
      level was observed in the hippocampal dentate gyrus after acute (cocaine) and
      chronic (cocaine, amphetamine) administration of the psychostimulants. The
      observed adaptive changes in the activity of two opioid systems in two structures
      of the limbic system, central nucleus of amygdala and hippocampus, may contribute
      to the neurochemical mechanism of drug addiction after psychostimulants. These
      studies also indicate that the changes in opioid gene expression in the central
      nucleus of the amygdala are not parallel to those observed in the nucleus
      accumbens after cocaine and amphetamine, which suggests that peptidergic systems
      in the structures of extended amygdala might be regulated by different
      neurochemical mechanisms after psychostymulant administration.

PMID- 12523491
TI  - Repeated treatment with selective serotonin reuptake inhibitors but not
      anxiolytics prevents the stress-induced deficit of fighting behavior.
AB  - Several animal models of "depression" have been examined. One of them is chronic
      unpredictable stress (CUS)-induced deficit of fighting behavior in rats. In the
      present study, we compared the effects of two antidepressants (fluoxetine or
      fluvoxamine) and three anxiolytics (buspirone, lorazepam or oxazepam) on the
      electric footshock-induced fighting behavior in the pairs of male Wistar rats
      exposed to CUS procedure (16-day application of various unpredictable stressors).
      It was found that, in chronically stressed rats, the number of fighting attacks
      was significantly reduced (by about 70%). Prolonged (for 14 days) treatment of
      rats with fluoxetine or fluvoxamine (both at the dose of 10 mg/kg/day)
      counteracted the deficit of aggression induced by the chronic stress. On the
      contrary, the anxiolytics: lorazepam (0.5 mg/kg/day), oxazepam (5 mg/kg/day) or
      buspirone (0.2 mg/kg/day) administered for 14 days, did not modify the deficit of
      fighting induced by CUS procedure. It must be underlined that prolonged treatment
      with all used drugs did not change the intensity of fighting in normal
      (unstressed) rats. In conclusion, prolonged treatment with antidepressant drugs
      prevents the CUS-induced deficit of fighting behavior, whereas no beneficial
      effect of anxiolytic agents was found.

PMID- 12523492
TI  - Effect of repeated treatment with mirtazapine on the central dopaminergic D2/D3
      receptors.
AB  - Mirtazapine (MIR) is an antidepressant drug which enhances noradrenergic and
      serotonergic 5-HT1A neurotransmission via antagonistic action at central alpha2
      adrenergic autoreceptors and heteroreceptors. We reported earlier that tricyclic
      antidepressants administered repeatedly induced adaptive changes in the central
      dopaminergic D2/D3 receptors. Therefore, we designed our present study to
      determine whether repeated MIR treatment could evoke similar effect. The
      experiments were carried out on male Wistar rats. MIR was administered at a dose
      of 10 mg/kg once or repeatedly (twice daily for 14 days). The obtained results
      showed that MIR administered repeatedly potentiated the hyperlocomotion induced
      by D-amphetamine but not by quinpirole or 7-OH-DPAT. Biochemical study showed
      that MIR administered repeatedly decreased the binding of [3H]quinpirole (a D2/D3
      receptor agonist) in the shell part of the nucleus accumbens septi and in the
      islands of Calleja but did not change the binding in the nucleus caudatus (medial
      or lateral). On the other hand, both acute and repeated drug treatment did not
      change the [3H]7-OH-DPAT (a D3 receptor agonist) binding sites in the islands of
      Calleja as well as in the shell part of nucleus accumbens septi. In addition, MIR
      did not alter the level of mRNA encoding dopamine D2 receptors, not only after
      repeated but also after acute treatment. The above results indicate that repeated
      MIR administration did not induce any adaptive change (behavioral and biochemical
      changes) in the dopaminergic D2/D3 system.

PMID- 12523493
TI  - Pharmacological analysis of the hypothermic effects of NAN-190 and its analogs,
      postsynaptic 5-HT1A receptor antagonists, in mice.
AB  - In this study, we examined the role of 5-hydroxytryptamine (5-HT)1A and alpha1
      adrenergic receptors in the hypothermia induced by 1-(2-methoxyphenyl)-4-[4-(2
      phthalimido)butyl]-piperazine (NAN-190) and its analogs, 1-(2-methoxyphenyl)-4
      [(4-succinimido)butyl]piperazine (MM77) and trans-1(2-methoxyphenyl)-4-[4-(2
      phthalimido)cyclohexyl]piperazine (MP245), which--like NAN-190--showed a high
      affinity for 5-HT1A and alpha1-adrenoceptors. Administration of NAN-190 (a
      partial agonist of presynaptic and an antagonist of postsynaptic 5-HT1A receptors
      and alpha1-adrenoceptors), MM77 and MP245 (antagonists of postsynaptic 5-HT1A
      receptors), as well as 8-OH-DPAT (a 5-HT1A agonist) and prazosin (an alpha1
      adrenoceptor antagonist) induced a dose-dependent hypothermia in mice. The silent
      antagonist of 5-HT1A receptors, WAY 100635, which abolished the hypothermic
      effect of 8-OH-DPAT, inhibited the hypothermia induced by NAN-190 administered at
      a dose of 1 mg/kg (but not 2 mg/kg) and by MP245 (0.5 and 1 mg/kg), but failed to
      change the MM77 (1 and 4 mg/kg)-induced decrease in body temperature in mice. The
      alpha1-adrenoceptor agonist St 587, which reduced the hypothermic effect of
      prazosin, inhibited the decrease in body temperature evoked by NAN-190 at the
      higher dose and by MP245 at both the doses used, but did not affect the MM77
      induced hypothermia in mice. The obtained results suggest that the hypothermia in
      mice induced by NAN-190 and its constrained analog MP245 is connected with
      stimulation of 5-HT1A receptors and with blockade of alpha1-adrenoceptors,
      participation of these receptors not being equivalent, though. The origin of the
      hypothermia evoked by MM77 is still unknown.

PMID- 12523494
TI  - Using reverse transcription and a competitive polymerase chain reaction for
      quantification of alpha1B-adrenoceptor mRNA.
AB  - Molecular cloning studies have revealed the existence of three subtypes of alpha1
      adrenergic receptor (alpha1-AR), namely alpha1A, alpha1B and alpha1D. They are
      encoded by separate genes and have distinct pharmacological profiles. In rats'
      brain, the expression of mRNA for subtypes of an alpha1-AR is partially structure
      dependent. Our previous studies employing Northern blot analysis of mRNA have
      shown that in the hippocampus, where alpha1A predominates, the alpha1B receptor
      (alpha1B-AR) was almost undetectable. The goal of the present study was to
      establish the method of reverse transcription and competitive polymerase chain
      reaction (RT-cPCR) to quantify a steady state level of alpha1B-AR mRNA in the
      hippocampus, prefrontal cortex and thalamus, and to compare the alpha1B-AR'
      pattern of expression with that revealed by Northern blot analysis. Our results
      have shown that alpha1B-AR is similarly represented in the thalamus and
      prefrontal cortex. In the hippocampus, ten times lower expression of alpha1B mRNA
      has been demonstrated with RT-cPCR, which was below a detection limit of Northern
      blot hybridization technique.

PMID- 12523495
TI  - Perazine as a potent inhibitor of human CYP1A2 but not CYP3A4.
AB  - The effects of perazine on the activities of CYP1A2 and CYP3A4 in a primary
      culture of human hepatocytes of one patient were studied in vitro. The CYPs
      activities were assessed by measuring the rate of acetanilide 4-hydroxylation
      (CYP1A2) and cyclosporine A oxidation (CYP3A4) after treatment with TCDD (a CYP1A
      subfamily inducer) or rifampicin (mainly a CYP3A4 inducer). The amounts of the
      metabolites formed in hepatocytes were assayed in the extracellular medium using
      the HPLC method. TCDD and rifampicin induced the formation of 4
      hydroxyacetanilide and cyclosporine A metabolites (monohydroxycyclosporine A,
      dihydroxycyclosporine A, N-desmethylcyclosporine A), respectively. The formation
      of 4-hydroxyacetanilide was strongly inhibited by three different concentrations
      of perazine (10, 25 and 50 microM) reaching 8, 3 and 2% of the control value,
      respectively. In the case of CYP3A4 activity, no such an effect of perazine was
      observed. Perazine showed only a week inhibition of the activity of cyclosporine
      A oxidase (to 96-86% of the control value). The obtained results suggest a strong
      inhibitory effect of perazine on human CYP1A2 activity with predicted Ki value
      similar to those of the known for CYP1A2 inhibitors, such as furafylline and
      fluvoxamine.

PMID- 12523496
TI  - Regulation of glucose transport in human skeletal muscle.
AB  - Glucose transport, the rate limiting step in glucose metabolism in skeletal
      muscle, is mediated by insulin-sensitive glucose transporter 4 (GLUT4) and can be
      activated in skeletal muscle by two separate and distinct signalling pathways:
      one stimulated by insulin and the second by muscle contractions. Skeletal muscle
      is the principal tissue responsible for insulin-stimulated glucose disposal and
      thus the major site of peripheral insulin resistance. Impaired glucose transport
      in skeletal muscle leads to impaired whole body glucose uptake, and contributes
      to the pathogenesis of Type 2 diabetes mellitus. A combination of genetic and
      environmental factors is likely to contribute to the pathogenesis of Type 2
      diabetes mellitus; however, the primary defect is still unknown. Intense efforts
      are underway to define the molecular mechanisms that regulate glucose metabolism
      in insulin sensitive tissues. This review will present our current understanding
      of mechanisms regulating glucose transport in skeletal muscle in humans.
      Elucidation of the pathways involved in the regulation of glucose homeostasis
      will offer insight into the pathogenesis of insulin resistance and Type 2
      diabetes mellitus and may lead to the identification of biochemical entry points
      for drug intervention to improve glucose homeostasis.

PMID- 12523497
TI  - Wound pathophysiology, infection and therapeutic options.
AB  - Wound healing is a complex and highly regulated process that can be compromised
      by both endogenous factors (pathophysiological) and exogenous factors (micro
      organisms). Microbial colonisation of both acute and chronic wounds is
      inevitable, and in most situations endogenous bacteria predominate, many of which
      are potentially pathogenic in the wound environment. The risk of wound infection
      increases as local conditions favour bacterial growth rather than host defence.
      Consequently a primary objective in wound management is to redress the host
      bacterial balance, and this is most effectively achieved by ensuring that the
      wound is cleared of devitalised tissue and foreign bodies, the bacterial load and
      inflammation are controlled, and that adequate tissue perfusion is maintained.
      Although surgical debridement is the most rapid and effective technique for
      removing devitalised tissue, topical enzymes, moisture-retentive dressings,
      biosurgical therapy and vacuum therapy have been used as alternative approaches
      to wound cleansing and preparation. Topical antimicrobial agents continue to be
      used widely for preventing wound infection and current interest is focused on
      alternatives to antibiotics, such as antimicrobial moisture-retentive dressings,
      honey, essential oils and cationic peptides. In addition to the need to control
      wound microflora, unregulated inflammation caused by both micro-organisms and
      underlying abnormal pathophysiological conditions is a major factor associated
      with poor healing in chronic wounds. Consequently, therapeutic strategies that
      target chronic inflammatory processes are critical to wound progression. The
      success of future therapies will be dependent on a growing understanding of the
      pathophysiological processes and the host-bacterial interactions that
      significantly influence wound healing.

PMID- 12523498
TI  - The expression of cyclooxygenase-1 and -2 in proliferative endometrium and
      endometrial adenocarcinoma.
AB  - BACKGROUND: The activity of cyclooxygenase-2 (COX-2) is increased in inflammation
      and in several cancer types. We investigated the expression of COX-2,
      cyclooxygenase-1 (COX-1), nitric oxide synthase-2 (NOS-2) and nitric oxide
      synthase-3 (NOS-3) in normal proliferative and secretory human endometrium, and
      in endometrial adenocarcinoma. METHODS: Human endometrium was collected at
      hysterectomy. Seven samples were in proliferative and 11 samples in secretory
      stage. Twelve specimens from endometrial carcinoma were collected, as well.
      Immunohistochemistry was used to investigate the expression of COX-1, COX-2, NOS
      2 and NOS-3. RESULTS: COX-2 immunostaining was detected in most specimens of
      normal proliferative glandular epithelium (86%) and of endometrial carcinomas
      (92%). COX-2 staining was often detected in cancer cells on the border areas of
      the tumour and on the areas of invasive growth. Staining for COX-2 was seen in
      proliferative glands usually only in the basal layer of the endometrium. NOS-2
      was usually absent or negligible in proliferative endometrial glands and also in
      the cancer cells of endometrial adenocarcinomas. No staining for either COX-2 or
      NOS-2 was seen in specimens of secretory glandular epithelium. The expression of
      the constitutive COX-1 and NOS-3 was negligible or weak in the glandular
      epithelium of proliferative and secretory endometrium and in endometrial cancer
      cells. CONCLUSIONS: The expression of the inducible COX-2 but not of COX-1 is
      stimulated in the glandular epithelium of proliferative endometrium and in the
      cancer cells of human endometrial adenocarcinoma, in particular in those in the
      borders of carcinoma and spreading into lymphatic vessels.

PMID- 12523499
TI  - The roles of adulthood behavioural factors and familial influences in bone
      density among men.
AB  - BACKGROUND: A primary strategy in osteoporosis prevention is advice on exercise,
      smoking, and calcium intake, although its practical value is unclear. AIM: To
      investigate the roles of such factors on bone density (BMD) after considering the
      influences of familial aggregation (combined effects of genetics and familial
      influences) in Finnish men 35-69 years old. METHODS: We selected 105 male
      monozygotic twin pairs, with discordance in suspected determinants. RESULTS:
      Dietary calcium was associated with BMD of the femoral neck; and body weight and
      lifetime frequency of endurance and ball game sport activities were associated
      with both femoral neck and lumbar BMD. Occupational loading and smoking were
      associated with neither. However, age and familial aggregation explained 73% of
      the variance of BMD in both the femoral neck and lumbar spine; calcium intake
      explained 1% in femoral neck and lifetime exercise 1% in lumbar spine.
      CONCLUSIONS: The effects of dietary calcium and physical activity that are not
      'embedded' in the familial influences had very modest effects on the variance of
      BMD. Thus our chances of influencing BMD in later adulthood by targeting
      behavioural habits are likely to be limited. Interventions focused on childhood
      and the family unit may achieve more beneficial long-term results.

PMID- 12523500
TI  - Apoptosis in the beta cells: cause or consequence of insulin secretion defect in
      diabetes?
AB  - Pancreatic beta-cell dysfunction and insulin resistance are two interrelated
      defects in the pathophysiology of type 2 diabetes. Defects in peripheral insulin
      action precede the development of glucose intolerance, as the pancreas
      compensates for insulin resistance by increasing insulin production and
      secretion. This may be achieved by enhancing cellular secretory capacity or by
      increasing beta-cell mass. Over time, the pancreatic secretion of insulin becomes
      inadequate for the extent of insulin resistance, and the levels of fasting and
      postprandial glucose rise leading to the onset of frank hyperglycemia, which
      leads to reduction in beta-cell function and survival through a process referred
      to as glucose toxicity. There is increasing evidence that apoptosis is the main
      mode of pancreatic beta-cell death not only in type 1 but also in type 2
      diabetes. Recently, studies in knockout mice, human and rat islets, and
      pancreatic beta-cell lines demonstrated that defective insulin signaling in beta
      cells might play an important pathophysiological role by affecting both secretory
      function and cell survival. The purpose of this review is to present recent
      advances in understanding of the interrelationship between molecular mechanisms
      underlying defects in insulin secretion and beta-cell survival in type 2 diabetes
      caused by impaired activation of insulin signaling pathways.

PMID- 12523501
TI  - Induction of apoptosis in cancer: new therapeutic opportunities.
AB  - Autonomous cell proliferation is one of the hallmarks of cancer cells, driven by
      activated growth-promoting oncogenes. However, deregulated activation of these
      oncogenes also triggers apoptosis via multiple pathways. Among them, the ARF-p53
      pathway appears to play a major role in mediating oncogene-induced apoptosis.
      Consequently, suppression of apoptosis by inactivation of p53 and other tumor
      suppressors is central to tumor development. These findings have broad
      implications in understanding cancer genetics and therapy. They help define the
      roles for oncogenes and tumor suppressor genes in tumorigenesis. Furthermore, the
      notion that cancer cells often carry specific defects in apoptotic pathways but
      are inherently sensitive to apoptosis as a result of deregulated proliferation,
      offers numerous opportunities for manipulating apoptosis in directions of
      clinical application.

PMID- 12523502
TI  - Apoptosis in myocardial infarction.
AB  - Apoptosis, one of the major forms of cell death, has been implicated in different
      cardiovascular diseases. In this paper we review many of the different studies
      that have been performed to address the occurrence of apoptotic cell death
      associated with myocardial infarction. A definitive differentiation between
      apoptosis and other forms of cell death is still needed, mainly because of
      differences and limitations of the methods used for detection. In myocardial
      infarction apoptosis has been reported at acute stages of evolution in the
      ischemic area as well as in remote zones. In the ischemic area it might be a
      determinant of the final size of the infarct and it seems to depend on the
      presence of post-ischemic reperfusion. However, the incidence of apoptosis
      reported until now varies widely. In the myocardium remote from the ischemic area
      it might be associated with the progression towards heart failure. At present,
      the role and significance of apoptosis in myocardial infarction is rather
      inconclusive. Further studies are needed to solve methodological uncertainties
      and clarify the mechanisms involved in the process of cell death, which is
      particularly important as a basis for therapeutic interventions.

PMID- 12523504
TI  - Effect of ozonation on the biological treatability of a textile mill effluent.
AB  - Ozonation applied prior to biological processes, has proved to be a very
      effective chemical treatment step mostly for colour removal when soluble dyes are
      used in textile finishing operations. Its impact on biological treatability
      however has not been fully evaluated yet. This study evaluates the effect of
      ozonation on the quality of wastewater from a textile mill involving bleaching
      and reactive dyeing of cotton and synthetic knit fabric. The effect of ozonation
      on COD fractionation and kinetic coefficients defining major biological processes
      is emphasised. The results indicate that the extent of ozone applied greatly
      affects the remaining organic carbon composition in the wastewater. The relative
      magnitude of different COD fractions varies as a function of the ozone dose.
      Ozonation does not however exert a measurable impact on the rate of major
      biological processes.

PMID- 12523503
TI  - Programmed cell death: many ways for cells to die decently.
AB  - Apoptosis, a cell death programme mediated by the caspase family of cysteine
      proteases, is essential for appropriate removal of excess cells in many
      developmental and physiological settings. It would, however, be very dangerous
      for the organism to depend on a single protease family for clearance of unwanted
      and potentially dangerous cells. Indeed, the exclusive role of caspases in the
      execution of programmed cell death (PCD) has been challenged recently, and the
      understanding of the molecular control of alternative death pathways is emerging.
      Here, I review recently discovered triggers and molecular regulators of caspase
      independent cell death programmes and discuss their potential as therapeutic
      targets for the treatment of cancer.

PMID- 12523505
TI  - Thermal regeneration of granular activated carbons using inert atmospheric
      conditions.
AB  - Thermal regeneration is increasingly being used for the recovery of field-spent
      granular activated carbons (GAC) generated by the water treatment industry.
      Despite its commercial success, conventional methods using oxidising conditions
      (usually steam) are known to damage the porosity of the regenerated carbons, thus
      reducing their adsorption capacity and economic value. This paper presents a
      comparative investigation into the benefits of using inert conditions for the
      regeneration of field-spent GAC. For the purpose of this work, a sample of spent
      carbon was regenerated in nitrogen and in steam to different degrees of burn off.
      The resulting samples were analysed for their porosity and surface area
      characteristics using nitrogen gas adsorption, and for their aqueous adsorption
      capacities using phenol and methylene blue. Experimental results showed that
      steam was sightly more effective than nitrogen at regenerating the total
      micropore volume and BET surface area of the carbons. However, these benefits
      were largely counteracted by greater losses in the carbon yield and damage to the
      narrow microporosity. Carbons regenerated in nitrogen exhibited greater
      adsorption capacities for the adsorption of small molecular size compounds
      (phenol) from solution, while carbons regenerated in steam adsorbed larger
      molecular size compounds (methylene blue) more effectively. However, when product
      yields were taken into consideration, inert regeneration was found to produce
      significantly better results than steam regeneration. An optimum process
      temperature was determined to be 950 degrees C.

PMID- 12523506
TI  - Influence of dissolved oxygen on aqueous Cr(VI) removal by ferrous ion.
AB  - Hexavalent chromium [Cr(VI)] is a highly toxic and carcnogenic pollutant,
      introduced to the environment due to several industrial activities. Ferrous iron
      (Fe(II)], an important natural reductant of the Cr(VI), and its release from iron
      bearing materials is now becoming a viable alternative for transforming Cr(VI) to
      the relatively non toxic trivalent form of chromium [Cr(III)]. Cr(VI) removal by
      ferrous ion at different pH is widely discussed in the literature but the
      influence of dissolved oxygen on the Cr(VI) removal with respect to pH, is still
      a contradictory subject. In the present study a systematic approach has been made
      to estimate the Cr(VI) removal by ferrous ion in oxygen-free and oxygen
      containing aqueous solutions of pH 3 to 7. Quantitative analysis results suggest
      that the influence of dissolved oxygen on the Cr(VI) reduction starts at pH 4.
      Though, its effect appears to be in significant up to pH 6, becomes quite
      pronounced at pH 7 because nearly 10 to 12% less removal of the Cr(VI) was
      observed in the presence of the stoichiometric requirement of three equivalents
      of Fe(II) in oxygenated solution of pH 7. This was evidenced by carrying detailed
      spectrophotometric absorption measurements of the Cr(VI) in the presence of
      Fe(II) in its different equivalent ratios in oxygenated and deoxygenated
      solutions.

PMID- 12523507
TI  - Screening of Coprinus species for the production of extracellular peroxidase and
      evaluation of the enzyme for the treatment of aqueous phenol.
AB  - The production of extracellular peroxidase by twenty-five strains of Coprinus
      species was investigated for the purpose of its application to the removal of
      phenolic and other aromatic compounds from industrial waste streams. After
      initial screening experiments, the production of peroxidase by three superior
      strains of C cinererus UAMH 4103, UAMH 7907 and IFO 30116 was monitored over a 15
      day period. Peroxidase activity was detected after 3 days of growth and had
      reached itspeak another 6 days later. The peroxidase activity appeared to
      increase with a corresponding depletion of glucose concentration and rapidly
      declined immediately after the exhaustion of glucose. The effectiveness of the
      cultivated C. cinereus peroxidase (CIP) for the removal of aqueous phenol was
      evaluated in the presence and in the absence of additives including polyethylene
      glycol (PEG) and chitosan, and compared with those of purified horseradish
      peroxidase (HRP) and Arthromyces ramosus peroxidase (ARP). The addition of PEG
      and chitosan enhanced the efficiency of phenol transformation catalyzed by CIP by
      the factor of 1.5 and 1.3, respectively. Although the efficiency of phenol
      transformation was higher with CIP than those with purified HRP and ARP in the
      absence of addtives, its superiority diminished in the presence of PEG. This
      suggests that the by-products of fungal culture in the crude CIP solution,
      presumably polycarbohydrates and proteins, have protective effects on the enzyme
      against inactivation during catalytic transformation of phenol, and the addition
      of PEG provides small effects on further protection.

PMID- 12523508
TI  - Biosorption of heavy metals influenced by the chemical composition of Spirulina
      sp. (Arthrospira) biomass.
AB  - The capacity of Spirulina sp. cells with different chemical composition for Pb
      (II), Cd (II) and Cr (VI) sorption, was evaluated. Four different types of
      Spirulina biomass with a different chemical composition were tested. Two of them
      contained a high percentage of protein (68.95 +/- 0.30 and 63.73 +/- 0.25%) as a
      result of being cultivated in Zarrouk medium and exposedat two light intensities
      (66 micromol photon m(-2) s(-1) and 144 micromol photon m(-2) s(-1)) in batch
      cultures. A third type of biomass, cultivated in a "Complex" medium and exposed
      at 66 micromol photon (m-2) s(-1), contained a high percentage of lipids (30.08
      +/- 1.92. Finally, the fourth type of biomass was enriched in polysaccharides
      (25.54 +/- 0.51%) as a result of being cultivated in the "Complex" medium, but
      exposed at 144 micromol photon m(-2) s(-1). It was found that the chemical
      composition of Spirulina sp. cells did have a strong influence on their
      adsorption capacity. The maximum adsorption capacities (q(max)) for Pb and Cd
      were highest (172.41 and 54.05 mg g(-1) of cells, at pH 5.0 and 4.5 respectively)
      when cells exhibited the higher polysaccharide content. In the case of Cr VI, the
      highest q(max), was exhibited by cells cultivated in Zarrouk medium and showing
      the higher protein content (at pH 2.0). pH did not affect the adsorption of Pb II
      in the range of 3 to 5.5, nor of Cd in the range of 4 to 7. For Cr VI, adsorption
      was observed only at a pH equal to 2 or lower.

PMID- 12523509
TI  - Biosorption of nitrophenols on anaerobic granular sludge.
AB  - The sorption and desorption of 2-nitrophenol (2-NP), 4-nitrophenol (4-NP) and 2,4
      dinitrophenol (2,4-DNP) on live anaerobic granular sludge was studied at five
      different sorbate (nitrophenols) concentrations between 10 x 10(3) - 90 x 10(3)
      microg l(-1). Experiments were conducted at room temperature (29 +/- 2 degrees C)
      and at an initial pH of 7.5. The maximum uptake capacity of live anaerobic
      granular sludge was found to b e 1,427, 1,511 and 1,865 microg g(-1) VSS for 2
      NP, 4-NP and 2,4-DNP, respectively. The equilibrium data of three nitrophenols
      obeyed both Freundlich and linear isotherm models. Sorption was observed to be
      partially reversible. About 20-89%, 36-90% and 29-80% desorption was observed for
      10 x 10(3) - 90 x 10(3) microg l(-1) sorbate concentrations of 2-NP, 4-NP and 2,4
      DNP, respectively.

PMID- 12523510
TI  - A field based evaluation of household arsenic removal technologies for the
      treatment of drinking water.
AB  - Seven household treatment technologies for the removal of arsenic (Alcan, BUET,
      DPHE/DANIDA, Garnet, Sono, Stevens, Tetrahedron) were each evaluated using water
      from 63 different tube wells taken from 3 different regions of Bangladesh. The
      technologies that were evaluated were chosen from those that appeared user
      friendly, readily available and whose promoters were open to participate in the
      study. Arsenic concentrations in feed and treated waters were analysed by the
      PeCo 75 arsenic field test kit, AA-hydride generation and ICP-AES. Feed water
      arsenic concentrations were found to be up to 600 microg l(-1). The more advanced
      treatment methods using: activated alumina (Alcan, BUET); metallic iron (Sono);
      anionic exchange resin (Tetrahedron) and iron coagulation (Stevens) were found to
      be most easily used and efficiently reduced arsenic concentrations to below the
      Bangladesh drinking water standard (0.05 mg As l(-1)). The use of aluminium
      sulphate coagulants and permanganate oxidants in the DPHE/DANIDA technology
      introduced unacceptably high concentrations of aluminium and manganese into the
      treated waters and are not recommended in household water treatment applications.
      While arseric concentrations were initially considered to be of paramount
      importance, it became clear that such technologies can increase the risk of
      bacterial contamination in the treated water and this needs serious consideration
      as this could create a hazard much greater than the arsenic contained in the
      water. Ground waters sampled during the course of this study were mostly found to
      be bacteria free. To minimize any risks relating to bacterial contamination the
      addition of hypochlorite or the boiling of water is necessary.

PMID- 12523511
TI  - Anaerobic treatment of polyethylene glycol of different molecular weights.
AB  - Biodegradation of high molecular weight polyethylene glycol has been found
      difficult under aerobic conditions. The use of a chemical treatment prior to the
      aerobic one was necessary to remove high molecular weight of polyethylene glycol.
      Anaerobic treatment of polyethylene glycol may present an alternative to
      integrated chemical and biological treatment for the elimination of this
      compound. Anaerobic biodegradation of polyethylene glycol from 200 to 10,000
      molecular weight was studied. It showed that, unlike aerobic treatment, the size
      of the molecule up to 10,000 does not affect the process efficiency. The critical
      retention time and the optimum retention time were estimated and ranged from 10
      to 14 and from 16 to 19 days, respectively. Under these operational conditions
      percentage of removal ranged from 85 to 90%. Thus, anaerobic degradation of
      polyethylene glycol presents removal percentages and hydraulic retention times
      compounds similar to those of biodegradable tested at the same operational
      conditions.

PMID- 12523512
TI  - Removal of dissolved natural organic matter from source water with alum
      coagulation.
AB  - In this study, the effectiveness of enhanced alum coagulation for removal of
      natural organic matter (NOM) at various alum dosages and pH conditions was
      assessed for three source waters. Results from the laboratory jar tests at
      various conditions were compared. Tested pH ranged from 5.0 to 8.0, with alum
      dosages ranging from 60-120 mg l(-1) for removal of dissolved NOM with various
      concentration of dissolved organic carbon (DOC) and alkalinity. Alum coagulation
      profiles of the three source waters were also compared. For Cheng-Kung Water
      Treatment Plant (high DOC, high alkalinity), laboratory tests showed 50% DOC
      removal with alum dosage of 70-110 mg (-1). after acidifying the raw water to pH
      = 6. For Tai Lake Water Treatment Plant (high DOC, low alkalinity), laboratory
      tests showed that the highest DOC removal (approximately 50%) was achieved at an
      alum dosage of 80 mg l(-1) at pH = 8 (natural condition). However, alum
      coagulation showed little DOC removal for source water from Kee-Lung River (low
      DOC, low alkalinity). Higher alkalinity in Cheng-Kung Reservoir accounts for the
      necessity to acidify the raw water before enhanced coagulation for optimum DOC
      removal.

PMID- 12523513
TI  - The development of PM emission factor for small incinerators and boilers.
AB  - This study is intended to develop the emission factors of particulate matter such
      as TPM (total particulate matter), PM-10 (particulate matter less than 10
      micrometers in aerodynamic diameter), PM-2.5 (particulate matter less than 2.5
      micrometers in aerodynamic diameters) and several types of inorganic matter from
      small-size incinerators (less than 250 kg hr(-1) capacity) and boilers (less than
      5 ton hr(-1) capacity a s steam generation) for various compositions of wastes
      and fuels, respectively.The emission factors for particulate matter from boilers
      were similar to the US EPA data. However, the emission factors from small
      incinerators were higher than the emission factors developed in other countries
      because the emission characteristics were different, especially with respect to
      the combustor's capacity. Emission factors for heavy metals such as cadmium,
      manganese, chromium, magnesium, lead, zinc, and copper were also investigated.
      The emission factors in this study were higher than those in other studies.
      Particle size distribution of PM-10 and the ratio of submicron PM to TPM were
      observed and a mode (peak) of submicron size particles together with a higher
      concentration of them was found, which could be explained by the formation of
      fines from vaporized metals wastes.

PMID- 12523514
TI  - Vertical transport of Cryptosporidium parvum oocysts through sediments.
AB  - A mathematical model is presented to describe the vertical transport of
      Cryptosporidium parvum oocysts through sediments. C. parvum oocyst has a particle
      diameter of 4.5-5.5 microm and density of 1.025-1.070 g cm3, and so the
      gravitational sedimentation may play a role in the vertical transport of the
      oocysts. The setting velocity of the oocystsis calculated and on saturated porous
      media, was found to be between 2.2 x 10(-5) a nd 8.9 x 10(-5) cm sec(-1). The
      permeability of porous media may be altered due to the deposition of the oocysts
      on the solid matrix. In the simulation, the permeability change is determined
      with an equation from other researches. The model equations are used to simulate
      the experimental data of an ealier work by other authors and the numerical
      results show a good fit with them. Simulation results show that when the oocyst
      suspension is injected continually, the relative permeability of sediments
      decreases since the volume of theoocysts deposited on the solid matix increases.
      Sensitivity analysis demonstrates that the profile of the relative permeability
      is very sensitive to the change of the irreversible deposition rate coefficient
      of the oocysts, k(ci). As k(ci) increases, the volume of the oocysts immobilized
      around the inlet boundary increases, resulting in the decrease of the relative
      permeability.

PMID- 12523515
TI  - Perceived and real risks: produced water from oil extraction.

PMID- 12523516
TI  - The three screen doors: can marine "protected" areas be effective?
AB  - The great majority of marine protected areas (MPAs) fail to meet their management
      objectives. So MPAs can be effective conservation tools, we recommend two
      paradigm shifts, the first related to how they are located and the second related
      to how they are managed. MPAs are unlikely to be effective if they are located in
      areas that are subject to numerous, and often uncontrollable, external stressors
      from atmospheric, terrestrial, and oceanic sources, all of which can degrade the
      environment and compromise protection. MPA effectiveness is also limited by low
      institutional and community capacity for management and inappropriate size with
      respect to ecological needs. In particular, the check list approach to management
      does not ensure that key threats are dealt with, or that management expenditures
      provide a quantifiable return. We recommend a business planning approach to MPA
      management, in which managers focus on the viability of the management system,
      i.e., the ability of the MPA to provide ecological goods and services to its
      target users over the long term.

PMID- 12523517
TI  - Impact of offsite sediment transport and toxicity on remediation of a
      contaminated estuarine bay.
AB  - Sediment of Ostrich Bay, an arm of Dyes Inlet on Puget Sound, was historically
      contaminated with ordnance compounds from an onshore US Navy facility. An initial
      recommendation for a sediment cover to mitigate benthic risks was followed by
      studies of sediment transport and deposition to determine whether contaminated
      sediment from Dyes Inlet or other offsite sources in Puget Sound may contribute
      to Ostrich Bay impacts. A Sediment Trend Analysis (STA) identified net sediment
      transport pathways throughout the bay and inlet by examining changes in grain
      size distributions in multiple adjacent samples. Results indicated that fine
      grained sedimentary material transports into and deposits throughout the Dyes
      Inlet system, with no erosion or transport out of Ostrich Bay. Echinoderm larvae
      mortality bioassay results were elevated in fine-grained sediments of both
      Ostrich Bay and Dyes Inlet. Ordnance compounds were undetected, and although
      sediment mercury concentrations were elevated at 0.48-1.4 mg/kg in both
      waterbodies, the relationship with toxicity was weak. Results of the studies and
      sedimentation modeling indicate that impacted sedimentary material deposits
      throughout the Dyes Inlet/Ostrich Bay system from unknown sources and will
      prevent natural recovery of Ostrich Bay as well as negate long-term effectiveness
      of active remedial measures. Stakeholders have recognized that remediation of the
      bay can be achieved only after the toxicity of depositing sediment decreases.

PMID- 12523518
TI  - Quantitative aspects of inorganic nutrient fluxes in the Gazi Bay (Kenya):
      implications for coastal ecosystems.
AB  - Fluxes of dissolved inorganic nutrients: NH4+, NO2-, NO3-, PO4(3-) and Si(OH)4
      from nearshore sediments of Gazi Bay were measured in situ within mangrove,
      seagrass and coral reef biotopes using benthic flux bell-jar chambers of cross
      sectional area 0.066 m2 and volume 0.0132 m3. The objectives were: (1) to
      determine the influence of benthic fluxes, fluvial discharge and seasonal
      variations on the nutrient budget in the Bay waters; (2) to determine the effect
      of tidal and spatial variations on nutrient loads in the water column and (3) to
      establish the relative importance of the nutrient sources with regard to total
      community production of the Bay. The directly measured fluxes ranged from -270 to
      +148 micromol NH4+-N/m2/h; -60 to +63 micromol NO2(-)-N/m2/h; -79 to +41 micromol
      NO3(-)-N/m2/h; -79 to +75 micromol PO4(3-)-P/m2/h and +30 to +350 micromol
      Si(OH)4-Si/m2/h for and respectively. It was established that benthic fluxes are
      the major sources of dissolved inorganic NH4+, NO2- and Si(OH)4 while fluvial
      sources are important for NO3- and PO4(3-) into Gazi Bay waters. Seasonal
      variations had an appreciable effect on the PO4(3-) fluxes, N:Si ratio, river
      nutrient discharge, plankton productivity and important environmental factors
      such as salinity and temperature. Tidal and spatial variations had no significant
      effect on nutrient concentrations and net fluxes within the water column. The
      results imply that benthic fluxes are largely responsible for the nutrient
      dynamics of the nearshore coastal ecosystems especially where direct terrestrial
      inputs do not contribute significantly to the nutrient budget.

PMID- 12523519
TI  - Characterizing stress gene expression in reef-building corals exposed to the
      mosquitoside dibrom.
AB  - We characterize two genes expressed in Acropora cervicornis upon exposure to 0.5
      microg/l of dibrom, a pesticide used for mosquito control in the Florida Keys.
      Fragments of these genes were isolated, sequenced, and developed into
      chemiluminescent probes for Northern slot blots. Expression of target transcripts
      was detected in corals exposed to a variety of stressors including
      organophosphates, organochlorines, heavy metals, naphthalene, and temperature.
      Within the context of stressors examined, the D25 probe demonstrates toxicant and
      concentration specificity for organophosphates, whereas the D50 probe had broader
      specificity, detecting transcripts in corals exposed to dibrom, naphthalene, and
      temperature stress. After characterizing specificity in the lab, these probes
      were used on field samples taken from the Florida Keys. Both probes detected
      their targets in samples taken from the upper Florida Keys in August 2000.
      Preliminary search of sequence databases suggest similarity exists between D25
      and a thioesterase.

PMID- 12523520
TI  - Vertical mixing of oil droplets by breaking waves.
AB  - Oil spilled on a sea surface can be dispersed by a variety of natural processes,
      of which the influence of breaking waves is dominant. Breaking waves are able to
      split the slick into small droplets, facilitating oil mixing in the water column.
      Vertical dynamics of the droplets plays a major role in the oil mass exchange
      between the slick and the water column. In this paper a mathematical model of oil
      droplet mixing by breaking waves is developed. The model uses a kinetic approach
      to describe the vertical exchange of the droplets at the interface between the
      slick and the water column. The majority of the coefficients and parameters are
      conveniently combined into a single "mixing factor". The model is verified using
      sensitivity analysis and empirical formulae of other authors. The model permits a
      rapid estimation of the amount of dispersed oil under the breaking waves. The
      ultimate goal of the research is to parameterise influence of breaking waves on
      vertical mixing of oil droplets to be used in a general 3-D oil spill model.

PMID- 12523521
TI  - Impact of elevated ammonium on reproduction in two Hawaiian scleractinian corals
      with different life history patterns.
AB  - Elevated nutrients have the potential to disrupt reproduction in scleractinian
      corals, with consequent impacts on population dynamics. Reproduction in broadcast
      spawning (Montipora capitata) and brooding (Pocillopora damicornis) species was
      assessed following exposure to elevated ammonium in a microcosm experiment.
      Planulation in P. damicornis ceased following 4 months of ammonium exposure and
      did not recover until 3 months after termination of nutrient enrichment. Larval
      settlement and survivorship were not affected by ammonium enrichment. Few
      significant changes were found for reproductive parameters of M. capitata. There
      was a significant but small decrease in egg size (430 microm in control eggs to
      408 microm in eggs from ammonium enrichment treatments), but no differences in
      total fecundity or fertilization success. This may be related to the presence of
      zooxanthellae in the eggs of M. capitata, in contrast to changes in reproduction
      previously reported in Acropora species, whose eggs do not contain zooxanthellae.

PMID- 12523522
TI  - Weathering of an Arctic oil spill over 20 years: the BIOS experiment revisited.
      Baffin Island Oil Spill.
AB  - A small experimental oil spill was conducted on the northern tip of Baffin Island
      Nunavut, Canada (72 degrees 31' N, 79 degrees 50' W) in August 1981, and the
      natural weathering of the oil has been followed by periodic visits. This paper
      reports on the chemical composition of oil collected in August 2001. The vast
      majority of the initial oil has gone, but small patches remain. Some samples
      remain essentially unaltered despite their 20 years of exposure to the elements,
      while others show that biodegradation and photooxidation can play important roles
      in removing the majority of the components of the oil. Using
      17alpha(H)21beta(H)hopane as a conserved marker within the oil, we show that the
      most biodegraded sample has lost more than 87% of the hydrocarbons initially
      present, while another has lost a substantial proportion of its initial chrysene
      and alkylated congeners. Potential explanations for the different weathering
      patterns seen in samples collected from this small site are briefly discussed.

PMID- 12523523
TI  - First observations in a high rocky-shore community after the Erika oil spill
      (December 1999, Brittany, France).
AB  - The high mediolittoral rocky-shore community on the island of Groix (Brittany,
      France), was studied for the year immediately following the Erika oil spill
      (12/12/1999). The macrofaunal assemblages of three habitats (exposed bedrock,
      crevices, boulders) under three situations (non-impacted, impacted and not
      washed, impacted and washed) were monitored monthly. The assemblage of each
      habitat showed specific responses to the impacts and initiated various patterns
      of succession: the bed rock assemblage changed in terms of abundance but no
      species-richness variations occurred; in the crevices richness variations
      occurred both in the disappearance of some species and the immigration of
      opportunistic ones; the boulder assemblage lost many species and remained
      unstructured one year after the oil spill. These first results of this most
      recent oil spill in Europe, raised the question of the relative importance of
      habitat-species and species interactions on the community structure.

PMID- 12523524
TI  - Deterioration of eelgrass, Zostera marina L., meadows by water pollution in Seto
      Inland Sea, Japan.
AB  - Survival of transplanted Zostera marina L. (eelgrass) and environmental
      conditions (water quality, bottom sediments, sedimentation on leaves and flow
      regime) were studied concurrently in the center, edge, and at the outside of a
      eelgrass meadow located in a eutrophic coastal zone in northern Hiroshima Bay,
      Seto Inland Sea, Japan. Eelgrass transplants at the outside of the meadow
      declined significantly, whereas those at the center were consistently well
      established. Silt content in the bottom sediments at the outside was higher than
      that at the center. The sediment was oxic from the surface to 2 cm deep at the
      center, whereas those at the edge and the outside were reductive almost from the
      surface. The sediment characteristics typical in eutrophic water seemed to be a
      factor responsible for the deterioration of eelgrass meadows. Although suspended
      solid concentrations in the water columns were almost the same, the amount of
      sediments deposited on leaves of eelgrass at the outside was higher than that at
      the center of the meadow. The amount of the deposition at the outside seems to be
      enough to inhibit photosynthesis; i.e. photosynthetic photon flux density (PPFD)
      available for eelgrass was only 36% of that without any deposition. The
      deposition in the center, however, was small enough to allow 84% of the original
      PPFD. Flow rates, determined at 30 cm above the bottom, a half height of average
      eelgrass, suggested that the rate at the outside was not enough to remove
      deposited sediments from the surface of eelgrass leaves. Thus, the large amount
      of sediment deposition caused by water pollution and/or eutrophication seemed to
      be another factor to inhibit the survival of eelgrass at the outside edge of the
      meadow.

PMID- 12523525
TI  - Aquaculture-related trace metals in sediments and lobsters and relevance to
      environmental monitoring program ratings for near-field effects.
AB  - The study was undertaken to assess the marine environmental effects from feed and
      waste associated with aquaculture activities. Metal compositions of sediment,
      lobster, and feed were used to evaluate the extent of detectable effects at 0 m
      (under the cage) and 50 m distance. Sediments that were collected under the cages
      and were characterised as hypoxic or anoxic, showed elevated levels of Cu, Zn,
      organic carbon, and % <63 microm particles, and low Mn and Fe. At 50 m there was
      a major reduction in waste chemical impact. Using lobster, a bioindicator
      species, as a tool for detecting near-field impacts, showed accumulations of high
      Cu associated with active aquaculture sites. Chemical compositions and metal
      ratios normalised with organic carbon, were used to assess the sediment
      conditions associated with environmental monitoring program ratings (EMP--normal,
      hypoxic, and anoxic). Principal component analysis (PCA) was used to explore
      chemical data at all sites for differentiating normal, hypoxic and anoxic
      sediment conditions. Selected variables (Cu, Zn, Fe, Mn, organic carbon, and
      particles <63 microm) were sufficient for the PCA approach with >90% explainable
      variance of first two components. The groupings based on PCA and cluster analysis
      were similar to EMP classifications with some exceptions of mis-identification by
      EMP. The sediment chemistry components were valid indicators for evaluating
      marine environmental conditions and for assessing aquaculture operating sites.
      The developed techniques, using chemical variables in combination with EMP and
      the statistical approach should be useful to predict the effects of aquaculture
      practices and the suitability of aquaculture operations.

PMID- 12523526
TI  - Chlorophyll-deficient propagules of Avicennia marina and apparent longer term
      deterioration of mangrove fitness in oil-polluted sediments.
AB  - A correlation between petroleum hydrocarbon concentrations in sediments and
      chlorophyll-deficient mutations in mangroves may occur also in Australian
      mangroves. Earlier reports of such mutations in the Caribbean area were evident
      in viviparous propagules of the common mangrove genera, Rhizophora, borne on
      otherwise normal trees. These mutant propagules were termed albinos' since they
      lacked chlorophyll and normal green coloration, leaving them white, yellow or
      red. The mutation was considered lethal since newly established albino seedlings
      appeared unable to survive more than a few months. Our preliminary investigation
      of mangroves in SE Queensland found a similar mutation in another common mangrove
      genus, Avicennia, and this was apparently also correlated with oil concentrations
      in sediments. Although, more evidence is required, an apparently similar
      relationship shows that whatever caused the mutations may act commonly across a
      diverse range of plant types in quite separate locations. How widespread might
      this mutation be in mangroves? How many genera and species are affected? Are all
      occurrences correlated with oil in sediments? Does oil cause the mutation? We
      discuss these important questions and the potentially serious implications to
      coastal management where high mutant densities may be indicative of longer term
      genetic deterioration of mangrove habitat in oil-polluted wetland environments.

PMID- 12523527
TI  - Trace metal retention in mangrove ecosystems in Guanabara Bay, SE Brazil.
AB  - Along contrasting environmental conditions (e.g., degree of trace metal
      contamination and mangrove forest structural development), sediments of
      Laguncularia racemosa-dominated mangrove stands in Guanabara Bay (SE Brazil)
      presented a trend of trace metal accumulation in forms with low potential of
      remobilization and biotic uptake. Concurrently, a relatively low transfer of
      sediment-bound metals to L. racemosa leaves was observed, which may moderate the
      metal export from the forests via leaf litter transport and the metal
      availability to enter in food chains based on leaf consumption.

PMID- 12523528
TI  - Coral reef health and effects of socio-economic factors in Fiji and Cook Islands.
AB  - This research focuses on coral reef health in the South Pacific region, an area
      of high global coral diversity. Coral reef health surrounding four island case
      studies in the Cook Islands and Fiji have been assessed in areas that have not
      been previously surveyed. This study compares four islands with barrier and
      fringing reefs that have different levels of economic development, population
      pressure, land-use practices, and marine management practices. This
      interdisciplinary research methodology includes both ecological and social data
      collection to further understanding of human environment interactions. In
      comparing the reefs with different socio-economic factors, this research shows
      that reefs with traditional systems of resources management are healthier,
      population pressure is not the main factor causing the demise of the reefs and
      agro-industry is the main industry causing the degradation of the reef in these
      four South Pacific Islands. In addition, researchers need to use a whole reef
      perspective to examine coral reef health.

PMID- 12523529
TI  - Seabirds and floating plastic debris.
AB  - 80% of floating plastic debris freshly washed ashore on a Dutch coast showed
      peckmarks made by birds at sea. They either mistake these debris for cuttlebones
      or simply test all floating objects. Ingestion of plastic is deleterious for
      marine organisms. It is urgent to set measures to plastic litter production.

PMID- 12523530
TI  - Organochlorine concentrations in resident bottlenose dolphins (Tursiops
      truncatus) in the Shannon estuary, Ireland.

PMID- 12523531
TI  - Concentrations of selected trace metals (Cu, Pb, Zn), organochlorines (PCBs, HCB)
      and total PAHs in mangrove oysters from the Pacific Coast of Mexico: an overview.

PMID- 12523532
TI  - Trace metals in sediments from Torres Strait and the Gulf of Papua:
      concentrations, distribution and water circulation patterns.

PMID- 12523533
TI  - Higher contamination in the future population of developed nations.

PMID- 12523534
TI  - PAH phototoxicity--an ecologically irrelevant phenomenon?
AB  - Photoenhanced toxicity of polycyclic aromatic hydrocarbons (PAH) is well
      demonstrated in laboratory and in a few in situ studies. Effects have been
      observed for multiple taxa and toxicological endpoints, and the mechanism of
      toxic action has been described. However, this phenomenon is ameliorated by
      physical, chemical and biotic factors. The ecological relevance of PAH
      phototoxicity remains uncertain; it should not be used for environmental
      management decisions unless its ecological relevance is firmly established, and
      then only as part of a weight of evidence determination.

PMID- 12523535
TI  - Marine testing board for certification of ballast water treatment technologies.
AB  - The proposed MTB is a process to expedite the implementation of international
      standards and regulations, and the subsequent testing, certification, and
      regulatory approval of new ballast water treatment ("control") technologies. This
      would expedite their acceptance in the global marketplace and reduce risks of
      shipowners following international regulation. The cost to test and evaluate and
      certify new ballast water treatment technologies for the global marketplace has
      been estimated to be less than US $1 per day per ship. It is time for the
      shipping industry, national regulatory bodies, and IMO to endorse the concept of
      the MTB and for the shipping industry to support a proactive cost-saving solution
      for sustainable shipping and protecting the environment from unwanted invasions
      of aquatic species with their potential negative impacts.

PMID- 12523536
TI  - Dry deposition of reactive nitrogen to marine environments: recent advances and
      remaining uncertainties.
AB  - Many highly productive marine ecosystems exhibit nitrogen limitation or co
      limitation. This article is a status review of research into the exchange of
      nitrogen between the atmosphere and these ecosystems with a particular focus on
      reactive nitrogen compounds. A summary of research conducted over the past ten
      years is presented and a perspective given as to remaining uncertainities and
      research needs. Looking toward development of coastal management modeling tools,
      we illustrate the processes that need to be resolved in order to accurately
      simulate the flux from the atmosphere and provide guidance on the required
      resolution of such models.

PMID- 12523537
TI  - Isolation and characterization of Aeromonas species from an eutrophic tropical
      estuary.
AB  - Isolation and characterization of Aeromonas species were undertaken in the Ebrie
      lagoon (Abidjan, Cote d'Ivoire) over a one year period. Overall 63% of 501 water
      samples were identified as positive for Aeromonas spp. A. sobria, A. hydrophila
      and A. caviae represent respectively 49.20%, 20.63% and 30.15% of the positive
      samples. Thirty nine of the positive samples were recovered from surface water
      samples; while 24 bottom water samples were positive for Aeromonas. Aeromonas
      species are most frequently (82.53) present in the Ebrie lagoon urban area during
      the rainy and flood seasons when the salinity is low and below 10 per thousand. A
      lower isolation frequency is noticed during the dry season when water salinity is
      over 10 per thousand. Finally, a higher isolation frequency occurred in samples
      with highest counts of Escherichia coli.

PMID- 12523538
TI  - Spatial and temporal variation in hexachlorocyclohexane isomers in a temperate
      estuary.
AB  - Hexachlorocylcohexanes (HCHs) are pesticides that persist in air and water of the
      Northern hemisphere. To understand the spatial and temporal variability in HCH
      levels in estuarine surface waters we measured concentrations of two HCH isomers
      (alpha-HCH and gamma-HCH) at six sites in the York River estuary at bimonthly
      intervals for a year. Bacterial abundance and activity were also monitored using
      acridine orange direct counts and uptake of tritiated substrates, respectively.
      Alpha-HCH was consistently observed to be significantly higher in marine water
      compared to river water entering the estuary, suggesting that the Chesapeake Bay
      or Atlantic Ocean is a larger source of this compound to the York River estuary
      compared to riverine input. Moreover, following periods of high freshwater flow
      into the estuary during spring and early summer, both alpha- and gamma-HCH mixing
      curves indicated an additional source of these pollutants to the estuary such as
      land-derived runoff or groundwater discharge. In contrast, during low freshwater
      flow (late summer and fall) the estuary was a sink for HCHs, with y-HCH more
      rapidly removed from the estuary than alpha-HCH. During the period of low
      freshwater flow, concentrations of both alpha- and gamma-HCH were negatively
      correlated with bacterial activity. Bacterial activity as opposed to abundance
      appears to control HCH degradation in estuarine surface waters.

PMID- 12523539
TI  - Total and methylmercury residues in cartilaginous fish from Mediterranean Sea.
AB  - Concentrations of mercury and methylmercury residues were determined in the
      muscle tissue of three cartilaginous fishes Chimaera monstrosa (ghostshark),
      Torpedo nobiliana (electric ray) and Myliobatis aquila (eagle ray) from the
      Mediterranean Sea. The highest mean levels of total mercury were detected in
      ghostshark (3.14 mg/kg wet weight), followed by electric ray (2.42 mg/kg wet
      weight), and eagle ray (0.83 mg/kg wet weight). Such a variability is influenced
      by quite a number of factors, among which size, fish ecology and feeding habits.
      The percentages of the methylated form to total mercury ranged from a minimum of
      72% in eagle ray to a maximum of 83% in ghostshark. Relationship between specimen
      size and mercury and methylmercury concentrations were found in ghostshark
      species.

PMID- 12523540
TI  - Detecting genotoxicity using the Comet assay following chronic exposure of Manila
      clam Tapes semidecussatus to polluted estuarine sediments.
AB  - Sediments frequently cause damage to biota due to the accumulation of toxic
      compounds and the bioavailability of sediment-bound contaminants. Damage can be
      assessed using biomarkers, such as the degree of genotoxic impact following in
      vivo exposure to pollutants. Genotoxic damage, expressed as single-strand DNA
      breaks, was measured in cells isolated from haemolymph, gill and digestive gland
      from the clam Tapes semidecussatus, using the single cell gel electrophoresis
      (Comet assay). Clams were exposed for three weeks to sediment samples collected
      from a polluted site and a 'clean' reference site. The level of DNA damage was
      assessed using an image analysis package and expressed as Tail Moment. Throughout
      the study, significant differences in DNA damage were recorded for each tissue
      type between clams exposed to the two sediment samples. We conclude that the
      Comet assay is a useful tool for the detection of DNA damage in clams chronically
      exposed to polluted sediments.

PMID- 12523541
TI  - Bioaccumulation of radiocaesium in Arctic seals.
AB  - Seals are high trophic level feeders that bioaccumulate many contaminants to a
      greater degree than most lower trophic level organisms. Their trophic status in
      the marine food web and wide-spread distribution make seals useful sentinels of
      arctic environmental change. The purpose of this investigation is to document the
      levels and bioaccumulation potential of radiocaesium in high latitude seal
      species for which data have not previously been available. The study was carried
      out on harp, ringed, and bearded seals caught north of the island archipelago of
      Svalbard (82 degrees N) in 1999. The results are then compared with previous
      studies in order to elucidate factors responsible for bioaccumulation in Arctic
      seals. Concentrations of 137Cs were determined in muscle, liver and kidney
      samples from a total of 10 juvenile and one adult seal. The mean concentration in
      muscle samples for all animals was 0.23 +/- 0.045 Bq/kg f.w. 137Cs concentrations
      in both liver and kidney samples were near detection limits (approximately 0.2
      Bq/kg f.w.). The results are consistent with previous studies indicating low
      levels of radiocaesium in Arctic seals in response to a long term trend of
      decreasing levels of 137Cs in the Barents Sea region. Bioconcentration factors
      (BCFs) estimated for seals from NE Svalbard are low, ranging from 34 to 130.
      Comparing these values with reported BCFs for Greenland seals from other sectors
      of the European Arctic, we suggest that the combination of physiological and
      ecological factors on radiocaesium bioaccumulation is comparable among different
      Arctic seal populations. The application of this work to Arctic monitoring and
      assessment programs is discussed.

PMID- 12523542
TI  - Biofouling confounds the uptake of trace organic contaminants by semi-permeable
      membrane devices (SPMDs).
AB  - The outer layers of layflat, low density polyethylene plastic tubing (the
      principal component of semi-permeable membrane devices, SPMDs) were biofouled at
      a clean site in Hong Kong coastal waters for periods of 1-4 weeks. Following pre
      fouling, triolein was added to the SPMDs and, along with control (unfouled)
      devices, they were exposed to a range of organochlorine pesticides (alpha-HCH,
      aldrin, p,p'-DDT) and PAHs (anthracene, fluoranthene and benzo(a)pyrene) under
      laboratory conditions. Results showed that the uptake of contaminants by SPMDs
      was severely reduced by as much as 50% under fouling conditions in comparison to
      unfouled controls. The ultimate utility of SPMDs as passive monitors is thus
      reduced, although alternative measures, such as the use of permeability reference
      compounds may compensate, and allow for realistic evaluations of dissolved
      environmental concentrations in aquatic environments. However, due to the
      complexities involved in such procedures--especially as they need to be conducted
      on a case-by-case basis-the utility of SPMDs appears to be limited for estimates
      of bioavailability unless necessary calibrations are undertaken within each
      environment that the sampler is used.

PMID- 12523543
TI  - Coral bleaching on high-latitude marginal reefs at Sodwana Bay, South Africa.
AB  - Coral bleaching, involving the expulsion of symbiotic zooxanthellae from the host
      cells, poses a major threat to coral reefs throughout their distributional range.
      The role of temperature in coral bleaching has been extensively investigated and
      is widely accepted. A bleaching event was observed on the marginal high-latitude
      reefs of South Africa located at Sodwana Bay during the summer months of 2000.
      This was associated with increased sea temperatures with high seasonal peaks in
      summer and increased radiation in exceptionally clear water. The bleaching was
      limited to Two-mile Reef and Nine-mile Reef at Sodwana Bay and affected <12% of
      the total living cover on Two-mile Reef. Montipora spp., Alveopora spongiosa and
      Acropora spp. were bleached, as well as some Alcyoniidae (Sinularia dura,
      Lobophytum depressum, L. patulum). A cyclical increase in sea temperature (with a
      period of 5-6 years) was recorded during 1998-2000 in addition to the regional
      temperature increase caused by the El Nino Southern Oscillation phenomenon. The
      mean sea temperature increased at a rate of 0.27 degrees Cyear(-1) from May 1994
      to April 2000. High maximum temperatures were measured (>29 degrees C). The
      lowest mean monthly and the mean maximum monthly temperatures at which coral
      bleaching occurred were 27.5 and 28.8 degrees C, respectively, while the duration
      for which high temperatures occurred in 2000 was 67 days at > or = 27.5 degrees C
      (4 days at > or = 28.8 degrees C). Increased water clarity and radiation appeared
      to be a synergistic cause in the coral bleaching encountered at Sodwana Bay.

PMID- 12523544
TI  - Sea transport of animal and vegetable oils and its environmental consequences.
AB  - The increasing production-and therefore sea traffic--of vegetable oils has
      regularly led to spillages during the past 40 years. The accident of Allegra, on
      October,lst, 1997, in the English Channel gave rise to a spillage of 900 tonnes
      of palm nut oil. The drift of this solid vegetable oil was followed by aerial
      observations. Samples of oil were collected in order to analyse its chemical
      evolution. This study, associated with several bibliographic cases of pollution
      by non-petroleum oils, shows that drifting oils can mix with floating material to
      sink or form a crust. They can also be oxidized or disperse and/or be degraded by
      bacteria. They may also polymerise. The coating properties of vegetable oils act
      as crude oils to affect sea life, tourism and yachting. As a result, it is
      necessary to quickly collect the oil after a spillage, using usual equipment
      (booms and pumps).

PMID- 12523545
TI  - Consequences of a freshwater canal discharge on the benthic community and its
      habitat on an exposed sandy beach.
AB  - This paper analyses the spatial and temporal effects of a freshwater discharge
      (Canal Andreoni) on the macroinfauna community and its habitat in a sandy beach
      of Uruguay. Bimonthly, we examined 17 environmental variables plus macroinfauna
      abundance, biomass, richness, evenness and diversity of three sites: Andreoni, at
      the canal mouth, Coronilla, at 1 km, and Barra, at 13 km from the mouth. Both
      univariate and multivariate techniques showed an increasing degree of
      perturbation towards the canal. This was reflected by abiotic and biotic
      differences between sites and by a consistent two-dimensional ordination of the
      samples. A clear seasonal pattern was found, specially accentuated at Coronilla,
      where the effects of the canal were stronger in winter and weaker in summer.
      Multivariate linking between macroinfauna and its habitat highlighted the role of
      salinity as explanatory variable of the observed trends.

PMID- 12523546
TI  - Toxicity of 1,4-dichlorobenzene in sediments to juvenile polychaete worms.
AB  - Investigation of sediment contamination associated with a marine sewage outfall
      in Victoria (BC, Canada) found elevated concentrations of 1,4-dichlorobenzene
      (1,4-DCB). Juvenile polychaete worm (Neanthes) growth was significantly reduced
      at or near the outfall, roughly corresponding to elevated 1,4-DCB concentrations.
      There are few data on 1,4-DCB toxicity to marine organisms and no published
      literature on its toxicity to benthic marine organisms. To determine whether
      reduced polychaete growth (measured as dry weight) was due to 1,4-DCB exposure, a
      laboratory investigation was conducted. Uncontaminated marine sediment was spiked
      with 1,4-DCB and juvenile Neanthes were exposed in 20-d sublethal toxicity tests.
      There were no adverse effects on survival at any test concentration; mean
      survival was 80-100%. Statistically significant decreases in average dry weight
      only occurred at the highest 1,4-DCB concentration (19,900 microg/kg, dry
      weight); this represented a 1,4-DCB concentration more than 10 times higher than
      previously measured at the outfall (1,710 microg/kg, dry weight). There were no
      adverse effects on survival or dry weight at the range of concentrations
      previously measured in sediments from the vicinity of the outfall.

PMID- 12523547
TI  - Mercury levels in coral reefs along the Caribbean coast of Central America.
AB  - Sediment and coral skeleton samples from 23 coral reefs along the Caribbean coast
      of Costa Rica and Panama (1497 km) were evaluated for total mercury (Hg). High
      levels of pollution were found in the entire region with averages of 18.9 and
      71.3 ppb in coral skeletons and sediments respectively. Significantly higher
      contamination was found in Panamanian corals (21.4 ppb) while compared to Costa
      Rican reef sediments (85.9 ppb). Hg from several processes and non-point sources
      (e.g., erosion, runoff, flooding, mining, overuse of agrochemicals, industrial
      waste, ports, and refineries) may have affected the entire region. The widespread
      observed distribution suggests that Hg is being carried along long distances
      within the region due to its high concentrations found in "pristine" reefs.
      Forest burning and colonial mining residues may be considered as possible
      contamination factors.

PMID- 12523548
TI  - PAH contamination of western Irish Sea sediments.
AB  - Concentrations of the sum of 15 PAHs in 22 surficial sediment samples from the
      western Irish Sea ranged from below 100 ng g(-1) in sandy sediments to a maximum
      of 1422 ng g(-1) in the centre of the mud basin. The concentrations are typical
      of coastal shelf sediments, but greater than those observed for aquatic sediments
      remote from known anthropogenic sources. Organic C and the % sediment <15 microm
      were positively correlated with sigmaPAH. sigmaPAH was normalised to organic C
      and particle size (i.e. expressed as sigmaPAH/C(org) and sigmaPAH/% < 15 microm)
      and significant relationships were still observed with organic C and % < 15
      microm. The results are discussed in the context of using organic C to normalise
      concentrations of PAHs to assess contamination levels in sediments.

PMID- 12523549
TI  - Organochlorine pesticides and PCB residues in sediments of Alexandria Harbour,
      Egypt.
AB  - Persistent organochlorine compound concentrations were determined for 23 surface
      sediment samples collected from Alexandria Harbor, Egypt. Total PCB
      concentrations ranged from 0.9 to 1210 ng/g with four to seven Cl-substituted
      biphenyls being the most prevalent PCBs congeners. Different PCB congener
      distribution patterns were observed, probably reflecting different inputs and
      attenuation at various locations. Total DDT concentrations varied from <0.25 ng/g
      to 885 ng/g. The ratios of DDTs (2,4'- and 4,4'-DDT)/total DDTs (DDTs plus
      metabolites) in sediment samples from certain sites were 0.86 or higher,
      indicating little attenuation or recent input of DDT. Total chlordane (the sum of
      heptachlor and its epoxide, oxy-, gamma- and alpha-chlordane and cis + trans
      nonachlor) ranged from <0.25 to 44 ng/g with the highest concentration found in
      the Arsenal Basin. The geographic distributions of PCBs, total DDTs and total
      chlordane were similar. Chlorinated benzenes (CBs), hexachlorocyclohexanes
      (HCHs), aldrin, dieldrin, endrin, chloropyrifos, endosulfan, mirex and
      pentachloroanisole were below detection limits or detected at low concentrations
      in most of the samples. Sites that were contaminated with high concentrations of
      organochlorine compounds were associated with dense population and low energy
      environment. The contamination levels of PCBs, total DDTs and total chlordane
      were in high range compared to other locations worldwide.

PMID- 12523550
TI  - When does a ganglion become a brain? Evolutionary origin of the central nervous
      system.
AB  - A brain, a neural structure located in the head, differs from a ganglion by the
      following characteristics: (1) a brain subserves the entire body, not just
      restricted segments; (2) it has functionally specialized parts; (3) it is
      bilobar; (4) commissures and neurons form the surface with axons in the central
      core; (5) interneurons are more numerous than primary motor or primary sensory
      neurons; and (6) multisynaptic rather than monosynaptic circuits predominate. A
      "cephalic ganglion" does not exist in any living animal and probably never
      occurred even in extinct ancestral species. It also is not a developmental stage
      in the ontogenesis of any vertebrate. Amphioxus may represent an intermediate
      stage in the evolution of the vertebrate nervous system, but the anatomic
      relationship between the notochord and neural tube is more complex. The
      decussating interneuron of amphioxus, to mediate a primitive coiling reflex away
      from any stimulus, provides a phylogenetic explanation for the pattern of crossed
      long ascending and descending pathways in the subsequent evolution of the
      vertebrate central nervous system. The evolution of the vertebrate central
      nervous system may have begun with free-living flatworms (planaria) that evolved
      before the divergence of metazoans into invertebrate and chordate branches. The
      planarian is the simplest animal to develop a body plan of bilateral symmetry and
      axes of growth with gradients of genetic expression, enabling cephalization,
      dorsal and ventral surfaces, medial and lateral regions, and an aggregate of
      neural cells in the head that form a bilobed brain. Neurons of the planarian
      brain more closely resemble those of vertebrates than those of advanced
      invertebrates, exhibiting typical vertebrate features of multipolar shape,
      dendritic spines with synaptic boutons, a single axon, expression of vertebrate
      like neural proteins, and relatively slow spontaneously generated electrical
      activity. The planarian is thus not only the first animal to possess a brain, but
      may be the ancestor of the vertebrate brain.

PMID- 12523551
TI  - Congenital vascular malformations in childhood.
AB  - Congenital vascular malformations are an important group of vascular anomalies
      that occur very early in the pregnancy. Most of these malformations occur between
      the third and the seventh weeks of the embryonic development. Malformations can
      affect the arteries, veins, capillaries, and venous sinuses, involving an
      isolated vessel or a part of the vascular system. There are malformations that
      affect the vessel size or course, and others that show pathology of the wall
      anatomy of the vessel. Magnetic resonance angiography (MRA) is improving the
      study conditions of this pathology. Treatment of most of the vascular
      malformations--some of them giving clinical symptoms during adulthood--still
      constitutes a challenge.

PMID- 12523552
TI  - New insights into craniosynostosis.
AB  - Craniosynostosis is a congenital developmental disorder involving premature
      fusion of cranial sutures, often associated with multiple neurological
      manifestations. The perspective of this group of disorders has changed
      dramatically in the new era of molecular genetics. In the last decade a large
      literature with new concepts in craniosynostosis has appeared. More than 100
      syndromes associated with craniosynostosis have been described, and in about a
      dozen, the molecular defect has been identified. Pediatric neurologists are less
      aware than geneticists, neurosurgeons, and craniofacial surgeons of these
      changes. General concepts about craniosynostosis are here presented with updates
      of clinical and genetic aspects of well-defined syndromes such as Apert, Crouzon,
      Pfeiffer, Saethre-Chotzen. Evidence of their relationship with fibroblast growth
      factor receptors (FGFRs) 1, 2, and 3, and with causative genes such as TWIST has
      been documented. New and other less common syndromes also are discussed. The
      differences between positional and synostotic plagiocephaly are important, as
      well as the cause of nonsyndromic craniosynostosis. The prognosis and
      neurological outcome of patients, including "benign" forms of craniosynostosis,
      are other important aspects. Major advances have occurred in understanding
      pathogenesis, diagnosis, and treatment of craniosynostosis. The role of local
      dura mater and apoptosis; modalities of imaging such as prenatal ultrasound and
      three-dimensional and spiral CT have improved the accuracy in diagnosis, and the
      new approaches in surgical treatment involving efficient and less invasive
      methods, are evidence of these advances.

PMID- 12523553
TI  - Agenesis and dysgenesis of the corpus callosum.
AB  - Agenesis and dysgenesis of the corpus callosum is a frequent anomaly that
      presents with a spectrum of clinical features and exhibits variable findings in
      neurological studies. Clinical signs and symptoms are the result of cerebral and
      extracerebral malformations associated with callosal dysgenesis. Callosal
      agenesis may be an isolated anomaly or may be syndromic as part of more extensive
      malformations, metabolic and genetic disorders. The advent of modern techniques
      and equipment for neuroimaging have allowed us to define with more precision the
      type and severity of the callosal dysgenesis and accompanying other cerebral
      malformations. Molecular genetic studies allow the recognition and confirmation
      of new syndromes that until now were incompletely defined. In the context of
      these new pathologic entities, a new classification is proposed that may prove to
      be more useful than the traditional single category, "agenesis of the corpus
      callosum" and can serve as a basis for a later, more detailed, etiologic
      classification that integrates morphology and molecular genetics.

PMID- 12523554
TI  - Role of Cajal-Retzius and subplate neurons in cerebral cortical development.
AB  - A synaptic network is already formed in the marginal zone of the early
      telencephalon before the arrival of the first wave of radial migration of
      neuroblasts from the subventricular zone to form the cortical plate. Cells and
      fibers forming the marginal zone are mainly the Cajal-Retzius (C-R) neurons and
      their processes. The origin of these cells is not yet proved but is likely either
      the median ganglionic eminence or the mesencephalic neuromere. The bipolar or
      multipolar C-R neurons populate the molecular layer of the fetal cortical plate
      and are sparse in the adult. Their thick axon emits collaterals for synaptic
      contact with pyramidal neurons initially in layer 6 and later with in all layers.
      C-R neurons produce GABA, possibly ACh, several calcium-binding proteins (eg,
      calmodulin, parvalbumin, calretinin) and several neuropeptides; they are rich in
      ribosomes. Subplate neurons, beneath the cortical plate, emit pioneer axons in
      the incipient formation of the internal capsule and also commissural fibers of
      the early hippocampus. C-R cells express products of the genes RELN, LIS1, and DS
      CAM, which mediate radial neuroblast migration and lamination of the cortical
      plate and important in the pathogenesis of lissencephaly. A subpopulation of C-R
      neurons also expresses a p53 product implicated in cell survival and apoptosis.
      In addition to forming the first intrinsic synaptic circuits of the cortical
      plate and its first afferent and efferent connections with subcortical
      structures, they may play additional roles in the formation of ocular dominance
      columns, in regulating neuronogenesis, and in cortical repair. They do not
      disappear by apoptosis at the completion of cell migration, as was previously
      thought, but their functional role in the mature brain remains unknown.

PMID- 12523555
TI  - Holoprosencephaly: genetic, neuroradiological, and clinical advances.
AB  - Recent advances in genetics and neuroimaging have greatly contributed to our
      understanding of the spectrum of midline brain and craniofacial malformations
      known as holoprosencephaly. This review summarizes our current understanding of
      the epidemiology and molecular-genetic bases of these malformations, as well as
      recent neuroradiological and clinical studies, which have revealed that the
      manifestations of holoprosencephaly are far more variable than previously
      appreciated. We also discuss the implications for and importance of accurate
      diagnosis, prognosis, management of common medical problems, and counseling for
      affected families.

PMID- 12523556
TI  - Malformations of the posterior fossa: current perspectives.
AB  - Posterior fossa malformations are a special group of central nervous system
      anomalies that present during infancy with hypotonia, developmental delay,
      microcephaly, or hydrocephalus. Recent discoveries of the genetic and epigenetic
      factors that control hindbrain ontogenesis explain some of these disturbances in
      cerebellar development. A comprehensive classification of posterior fossa
      malformations is proposed with particular attention to Dandy-Walker malformation,
      Joubert syndrome, and other cerebellar hypoplasias. A rare form of cerebellar
      hypertrophy which caused repeated obstruction at the foramen magnum is
      recognized. The importance of the cerebellum in language, cognition, and brain
      growth is stressed.

PMID- 12523557
TI  - Molecular genetic and morphologic integration in malformations of the nervous
      system for etiologic classification.
AB  - Molecular genetics has brought new insight into the etiology and pathogenesis of
      nervous system malformations, and provided a means of precise genetic diagnosis
      including the prenatal detection of many cerebral dysgeneses. Many cerebral
      malformations previously thought to be a single disorder are now known to be
      common end results of many independent genetic mutations. Examples are
      holoprosencephaly and lissencephaly. Gradients of genetic expression along the
      axes of the neural tube established at the time of gastrulation may explain many
      varieties and clinical expressions of cerebral malformations, including the
      involvement of non-neural tissues, such as midfacial hypoplasia from defective
      neural crest migration. A new classification of CNS malformations is proposed
      that integrates, but does not discard traditional morphologic criteria, but
      integrates them with new molecular genetic criteria.

PMID- 12523558
TI  - Arabidopsis ecotype variability in camalexin production and reaction to infection
      by Alternaria brassicicola.
AB  - Camalexin production was compared in 24 ecotypes of Arabidopsis thaliana.
      Detached Arabidopsis leaves were inoculated with Cochliobolus carbonum, an
      incompatible pathogen of Arabidopsis, to test the ability of each ecotype to
      produce camalexin. Whole plants were inoculated with Alternaria brassicicola, a
      crucifer pathogen, to determine if there was a correlation between the ability of
      an ecotype to produce camalexin and its resistance to A. brassicicola. All
      ecotypes were capable of producing camalexin, but the amounts produced relative
      to the Columbia ecotype (used as a standard) varied within and among ecotypes,
      and among experiments. Different degrees of resistance to A. brassicicola were
      observed among ecotypes, both macroscopically and microscopically. Extraction of
      A. brassicicola-inoculated leaves revealed that only four ecotypes (two resistant
      and two susceptible) produced easily detectable amounts of camalexin in response
      to this pathogen. TLC plate bioassays suggested that A. brassicicola was
      relatively insensitive to camalexin, thus casting some doubt on the importance of
      this compound in defense. These studies suggest that the role of camalexin in
      disease resistance varies among different Arabidopsis populations in nature, and
      they provide some clues to other possible determinants of resistance to A.
      brassicicola.

PMID- 12523559
TI  - Antifungal leaf-surface metabolites correlate with fungal abundance in sagebrush
      populations.
AB  - A central component in understanding plant-enemy interactions is to determine
      whether plant enemies, such as herbivores and pathogens, mediate the evolution of
      plant secondary metabolites. Using 26 populations of a broadly distributed plant
      species, sagebrush (Artemisia tridentata), we examined whether sagebrush
      populations in habitats with a greater prevalence of fungi contained antifungal
      secondary metabolites on leaf surfaces that were more active and diverse than
      sagebrush populations in habitats less favorable to fungi. Because moisture and
      temperature play a key role in the epidemiology of most plant-pathogen
      interactions, we also examined the relationship between the antifungal activity
      of secondary metabolites and the climate of a site. We evaluated the antifungal
      activity of sagebrush secondary metabolites against two fungi, a wild Penicillium
      sp. and a laboratory yeast, Saccharomyces cerevisiae, using a filter-paper disk
      assay and bioautography. Comparing the 26 sagebrush populations, we found that
      fungal abundance was a good predictor of both the activity (r2 = 0.36 for
      Saccharomyces, r2 = 0.37 for Penicillium) and number (r2 = 0.34 for
      Saccharomyces) of antifungal secondary metabolites. This suggests that selection
      imposed by fungal pathogens has led to more effective antifungal secondary
      metabolites. We found that the antifungal activity of sagebrush secondary
      metabolites was negatively related to average vapor pressure deficit of the
      habitat (r2 = 0.60 for Saccharomyces, r2 = 0.61 for Penicillium). Differences in
      antifungal activity among populations were not due to the amount of secondary
      metabolites, but rather to qualitative differences in the composition of
      antifungal compounds. Although all populations in habitats with high fungal
      prevalence had secondary metabolites with high antifungal activity, different
      suites of compounds were responsible for this activity, suggesting independent
      outcomes of selection on plants by fungal pathogens. The location of antifungal
      secondary metabolites on the leaf surface is consistent with their putative
      defense role, and we found no evidence supporting other functions, such as
      protection from ultraviolet light or oxidation. That the antifungal activity of
      sagebrush secondary metabolites was similar for two different fungi provides
      support for broad antifungal defenses. The incidence and severity of fungal
      disease in the field (caused by Puccinia tanaceti) were similar in moist and dry
      habitats, possibly reflecting an equilibrium between plant defense and fungal
      attack, as sites with greater fungal abundance compensated with more effective
      secondary metabolites. The geographic correlation between fungal abundance and
      antifungal secondary metabolites of sagebrush, coupled with our other data
      showing heritable variation in these metabolites, suggests that pathogenic fungi
      have selected for antifungal secondary metabolites in sagebrush.

PMID- 12523560
TI  - Effect of parthenin--a sesquiterpene lactone from Parthenium hysterophorus--on
      early growth and physiology of Ageratum conyzoides.
AB  - A study was undertaken to assess the effect of parthenin--a sesquiterpene lactone
      from Parthenium hysterophorus--on the germination, growth, and some associated
      physiological changes in Ageratum conyzoides. The study reveals that germination
      and growth of A. conyzoides was severely reduced by parthenin in the
      concentration range of 50, 100, and 200 microM, while at 400 microM a complete
      inhibition of germination was observed. The radicle length of A. conyzoides was
      reduced more than the plumule length. Further, the content of the photosynthetic
      pigment chlorophyll was appreciably reduced in the leaves of test plants spray
      treated with parthenin at 200 microM concentration. However, this inhibitory
      effect declined with the passage of time and at 10 days after treatment only a
      25% reduction in chlorophyll content was observed compared to 76% on the first
      day after spray. Likewise, the cellular respiration measured through 2,3,5
      triphenyl tetrazolium chloride was found to be less in the treated leaves, and
      the inhibitory response also declined with time. The content of proteins and
      carbohydrates decreased with the passage of time after parthenin treatment. The
      specific activities of the enzymes protease and alpha- and beta-amylase were also
      adversely affected in the parthenin treated leaves. In the case of protease. the
      activity decreased with passage of time while those of the amylases increased.
      Thus, we conclude that parthenin affects the germination and growth of A.
      conyzoides by altering the contents of some macromolecules and the specific
      activities of some enzymes. Such observations may be helpful in further exploring
      parthenin's mode of action.

PMID- 12523561
TI  - (Z)-8-heptadecene from infested cells reduces the reproduction of Varroa
      destructor under laboratory conditions.
AB  - The parasitic mite Varroa destructor Anderson and Trueman, the most serious
      threat to apiculture in many countries of the world, reproduces inside honeybee
      brood cells. Previous research, using artificial cells for rearing the mite on an
      Apis mellifera larva, indicated that semiochemicals affecting the reproduction of
      Varroa destructor are released into such cells. In order to isolate these
      semiochemicals, infested artificial cells were extracted with hexane and the
      extract fractionated twice. Several unsaturated hydrocarbons were identified in
      the active fraction; some of them were released in higher amounts in case of
      infestation and were, therefore, bioassayed for their effect on the mite's
      reproduction. Of five alkenes tested under laboratory conditions, (Z)-8
      heptadecene, caused a 30% reduction in the mean number of offspring of mites
      reared in cells treated with this compound.

PMID- 12523562
TI  - Behavioral responses of the parsnip webworm to host plant volatiles.
AB  - Sixth instars of the parsnip webworm, Depressaria pastinacella, orient by
      olfaction to bud, male flowers, and female flowers of their primary host plant,
      Pastinaca sativa. Because octyl acetate and octyl butyrate are characteristic of
      tissues consumed by the sixth instar, we investigated the influence of these
      esters on webworm feeding behavior and chemo-orientation. Although octyl acetate
      and octyl butyrate are feeding deterrents, and octyl butyrate is an olfactory
      repellent, octyl acetate serves as an olfactory attractant. In olfactometers,
      webworms do not show a preference when given a choice between octyl acetate and
      host plant tissues. These findings suggest that octyl acetate is a sufficient cue
      for olfactory orientation. Such behavior may explain differences in the relative
      abundance of these esters observed among populations of wild parsnip under
      differential selection pressure from these insects.

PMID- 12523563
TI  - Behavioral and electrophysiological responses of natural enemies to synomones
      from tea shoots and kairomones from tea aphids, Toxoptera aurantii.
AB  - Olfactometer bioassays and electrophysiological studies showed that the lacewing,
      Chrysopa sinica, the aphid parasitoid, Aphidius sp., and the coccinellid,
      Coccinella septempunctata, all responded to volatiles from tea aphids, Toxoptera
      aurantii, to hexane or ether rinses of tea aphid cuticles, and to synomones
      released by aphid-damaged tea shoots, as well as to the tea shoot-aphid complex.
      Each natural enemy spent more time searching on a filter paper treated with tea
      aphid honeydew than on a blank control filter paper. The interaction between
      synomones from aphid-damaged shoots and kairomones from tea aphids enhanced the
      responses to the plant-host complex. There was a significant, logistic dose
      response relationship between the number of natural enemies responding and the
      odor stimulus concentration. Volatile components from the plant-host complex,
      obtained by air entrainment, were identified by their mass spectra and retention
      times and confirmed by comparison with standard samples. These were (Z)-3-hexen-1
      ol, benzaldehyde, (E)-2-hexenal, (Z)-3-hexenyl acetate, ocimene, linalool,
      geraniol, indole, and (E)-2-hexenoic acid. The main components in a hexane rinse
      from tea aphid cuticle were benzaldehyde, undecane, 2,5-hexanedione, 2,5
      dihydrothiophene, linalool, 4-methyl-octane, and eicosane, whereas the main
      components from an ether rinse were (E)-2-hexenoic acid, heptadecane,
      pentadecane, eicosane, tetratetracontane, and nonadecane. Benzaldehyde elicited
      the strongest responses from natural enemies in theolfactometer and the largest
      electroantennogram (EAG) responses. While the amount of odor was small,
      Coccinella septempunctata was slightly more sensitive than Chrysopa sinica and
      Aphidius sp. An increase in doses of benzaldehyde, (E)-2-hexenal, and (Z)-3
      hexenyl acetate caused the EAG responses of each natural enemy to decrease. When
      the doses of (Z)-3-hexen-1-ol, linalool, and geranoil increased, EAGs of Chrysopa
      sinica and Aphidius sp. increased, but EAGs of Coccinella septempunctata
      decreased. When the dose of indole increased, EAGs of Coccineila septempunctata
      decreased, but those of Aphidius sp. increased. This study demonstrates that tea
      shoot-aphid complexes emit volatile synomones, while the odors from tea aphids,
      aphidcuticle extracts, and tea aphid honeydew contain kairomones, to which the
      natulal enemies show a logistic dose-response.

PMID- 12523564
TI  - Response to walnut olfactory and visual cues by the parasitic wasp
      Diachasmimorpha juglandis.
AB  - Diachasmimorpha juglandis is a specialist parasitoid attacking fly larvae in the
      genus Rhagoletis that feed exclusively on walnut fruit husks. In a free-foraging
      assay comparing response to uninfested, infested, and mechanically damaged
      fruits, we first determined that D. juglandis use host feeding damage on the
      fruit as a cue for host presence. In another free-foraging assay that used
      artificial walnut models and wind tunnel experiments, D. juglandis distinguished
      infested from uninfested fruits by using either olfactory or visual cues
      separately. However, the response rate of wasps in the wind tunnel was raised
      considerably when visual cues were also available. We analyzed the volatile
      compounds emitted by cohorts of uninfested, mechanically damaged, and infested
      fruits 1, 3, 5, 8, and 10 days after oviposition by flies into the infested
      fruits. Total volatile emissions did not differ significantly among treatments,
      but quantitative changes in volatiles distinguished infested fruits from
      uninfested and damaged fruits. The fact that parasitoids did not distinguish
      between infested and damaged fruits in assays where damage was visible indicates
      that they rely on visual cues when those are available.

PMID- 12523565
TI  - Impact of polyphenols on growth of the aquatic herbivore Acentria ephemerella.
AB  - Larvae of Acentria ephemerella live fully submerged, feeding on submersed aquatic
      angiosperms such as pondweeds (Potamogeton spp.) and Myriophyllum spicatum. Only
      the latter contains high concentrations of hydrolyzable tannins known to
      interfere with the growth of insect herbivores. We tested whether larvae grow
      faster on Potamogeton perfoliatus or M. spicatum and whether this is due to
      polyphenols in their food source. Larvae originating from the same egg clutch
      grew faster and larger on P. perfoliatus than on M. spicatum. The same growth
      response was observed with larvae that spent winter diapause on either P.
      perfoliatus or M. spicatum. These larvae were fed either with their host plant or
      the other macrophyte. No prior feeding effect was found, but growth of larvae
      reared on M. spicatum was less than when grown on P. perfoliatus. Larvae from
      another egg-clutch reared on M. spicatum, either from lake or cultivated in
      aquaria, exhibited reduced growth on the lake plants. P. perfoliatus contained
      less than 1% and M. spicatum (aquarium or field material) between 5 and 9%
      phenolic compounds. No differences in nitrogen content of leaves were found, but
      apical shoot sections of M. spicatum exhibited a significantly higher nitrogen
      content than P. perfoliatus. Our results indicate that hydrolyzable tannins are
      responsible for the reduced growth of Acentria when fed with M. spicatum.

PMID- 12523566
TI  - Chemical mediation of egg capsule deposition by mud snails.
AB  - Mud snails (Ilyanassa obsoleta = Nassarius obsoletus = Nassa obsoleta) deposit
      eggs in protective capsules on hard substrata in soft bottom environments. We
      studied sites of egg capsule deposition and snail movement responses to odors to
      determine if chemoreception plays a role in deposition site selection. From
      results of field surveys, laboratory experiments, and field experiments, we
      conclude that mud snails use chemoreception for capsule deposition. Attractive
      odors originate from mud snail and whelk egg capsules and from living bivalves.
      Evidence for attractive odors from conspecifics is equivocal. Capsules are
      deposited on living odor sources and nearby hard substrates. We hypothesize that
      deposition of capsules on living substrates increases the likelihood that embryos
      will survive by decreasing the chance of smothering of embryos by sediments.

PMID- 12523567
TI  - A complex, cross-taxon, chemical releaser of antipredator behavior in amphibians.
AB  - Prey species show diverse antipredator responses to chemical cues signaling
      predation threat. Among terrestrial vertebrates, the red-backed salamander,
      Plethodon cinereus, is an important species in the study of these chemical
      defenses. During the day and early evening, this species avoids rinses from
      garter snakes, Thamnophis sirtalis, independent of snake diet, but late at night.
      avoids only those rinses from garter snakes that have recently eaten P. cinereus.
      We tested whether the selective, late-night response requires the ingestion or
      injury of salamanders. In three experiments, we tested P. cinereus for their
      responses to separate or combined rinses from salamanders (undisturbed,
      distressed, and injured P. cinereus) and snakes (unfed, earthworm fed, and
      salamander-fed T. sirtalis). When paired against a water control, only rinses
      from salamander-fed snakes were avoided. When salamander treatments (undisturbed
      or distressed) were combined with the snake treatments (unfed or earthworm-fed)
      and tested against a water control, the combinations elicited avoidance. When
      selected treatments were paired against the standard rinse from salamander-fed
      snakes, only the combined rinses from salamanders and snakes nullified the
      avoidance response to the standard rinse. These data reveal a prey defense
      mechanism involving chemical elements fromboth the predatorand prey that does not
      require injury or ingestion of the prey in the formation of the cue.

PMID- 12523568
TI  - (Z,Z)-4,7-tridecadien-(S)-2-yl acetate: sex pheromone of Douglas-fir cone gall
      midge, Contarinia oregonensis.
AB  - Our objectives were to identify and field test the sex pheromone of female
      Douglas-fir cone gall midge, Contarinia oregonensis (Diptera: Ce-cidomyiidae).
      Coupled gas chromatographic-electroantennographic detection (GC-EAD) analyses of
      pheromone extract revealed a single compound (A) that elicited responses from
      male antennae. Hydrogenation of pheromone extract, followed by renewed GC-EAD
      analysis, revealed a new EAD-active compound with chromatographic characteristics
      identical to those of tridecan-2-yl acetate on five fused silica columns (DB-5,
      DB-210, DB-23, SP-1000, and Cyclodex-B). Syntheses, chromatography, and retention
      index calculations of all possible tridecen-2-yl acetates suggested that the
      candidate pheromone A was a tridecadien-2-yl acetate with nonconjugated double
      bonds. Synthetic candidate pheromone component (Z,Z)-4,7-tridecadien-2-yl acetate
      (Z4Z7) cochromatographed with A on all analytical columns and elicited comparable
      antennal activity. In GC-EAD analyses that separated the enantiomers (Z,Z)-4,7
      tridecadien-(S)-2-yl acetate (2S-Z4Z7) and (Z,Z)-4,7-tridecadien-(R)-2-yl acetate
      (2R-Z4Z7) with baseline resolution, only 2S-Z4Z7 as a component in a racemic
      standard or in pheromone extract elicited antennal responses. In Douglas-fir seed
      orchards, sticky traps baited with 2S-Z4Z7 captured male C. oregonensis, whereas
      2R-Z4Z7 was behaviorally benign. Comparable catches of males in traps baited with
      racemic Z4Z7 (50 microg) or virgin female C. oregonensis suggested that synthetic
      pheromone baits could be developed for monitoring C. oregonensis populations in
      commercial Douglas-fir seed orchards.

PMID- 12523569
TI  - Quantitative GC analysis of secondary alcohol pheromones: determination of
      release rate of red palm weevil, Rhynchophorus ferrugineus, pheromone from lures.
AB  - Aliphatic secondary alcohols are components of several aggregation pheromones of
      important beetle and weevil pests. Some of these pheromones are used frequently
      for the monitoring and mass trapping of the relevant insects. We encountered
      severe difficulties in direct GC quantitative analysis of these compounds.
      Therefore, we developed a simple GC analysis of secondary alcohols convening them
      to trifluoroacetyl derivatives and using secondary alcohol acetates as internal
      standards. This method was applied for the quantitative analysis of several
      secondary alcohols, including the aggregation pheromone components of the almond
      bark beetle and the red palm weevil. The release rate of the latter pheromone
      from commercial lures was also determined.

PMID- 12523570
TI  - Food experience on the predatory behavior of the ant Myrmica rubra towards a
      specialist moth, Acrolepiopsis assectella.
AB  - Entomophagous insects are often repelled by the secondary compounds of the plants
      eaten by their prey. These compounds, therefore, take on a defensive role for the
      phytophagous species that sequester them. Given that numerous entomophagous
      species are capable of learning, the effects on the foraging behavior of a
      repeated experience were investigated in the predatory ant Myrmica rubra. The
      sulfur amino acids methyl-cysteine sulfoxide (MCSO) and propyl-cysteine sulfoxide
      (PCSO) produced by Allium plants were identified in caterpillars of the leek moth
      Acrolepiopsis assectella. Three behavioral studies were carried out, with or
      without prior familiarization with caterpillars reared either on leek or on an
      artificial diet containing no Allium compounds. In choice tests with the two
      types of caterpillars, unfamiliarized ants displayed a preference for
      caterpillars reared on the artificial diet, but this preference disappeared or
      was reversed in both young and old ants after familiarization.

PMID- 12523571
TI  - Taste thresholds and suprathreshold responses to tannin-rich plant extracts and
      quinine in a primate species (Microcebus murinus).
AB  - Theories of plant chemical defenses discriminate between quantitative
      digestibility reducers (e.g., tannins) and qualitative toxins (e.g., alkaloids).
      Since the differential effect on taste of these compounds is poorly known, we
      recorded ingestive responses of a primate species, Microcebus murinus, to four
      tannin-rich plant extracts and to quinine, by using the behavioral method of the
      "two-bottle test." The efficiency of tannic extracts at precipitating protein was
      measured with the blue BSA method. Inhibition taste thresholds for tannins added
      to a moderately sweet solution varied between 0.25 and 2 g/l. The threshold for
      quinine hydrochloride was 0.32 g/l. The profiles of the response/concentration
      curves established for these astringent and bitter substances were similar, with
      maximal inhibition of consumption occurring for near-threshold concentrations.
      The large amounts of quinine required to deter this small-bodied species from
      feeding were unexpected, given its unspecialized frugivorous/insectivorous diet.
      We propose that the taste responses of Microcebus to tannins have been shaped in
      relation to the widespread occurrence of efficient polyphenols in food plants,
      while low responsiveness to quinine reflects a low risk of ingesting toxic
      alkaloids when feeding on ripe fruits and insects.

PMID- 12523572
TI  - Predicting toxicity of tall larkspur (Delphinium barbeyi): measurement of the
      variation in alkaloid concentration among plants and among years.
AB  - Tall larkspur (Delphinium barbeyi) is the principal mountain larkspur responsible
      for the majority of cattle deaths on mountain rangelands in western Colorado and
      central and southern Utah in the United States. Ten plants in each of two tall
      larkspur populations in the mountains near Ferron and Salina, Utah, were marked,
      and single stalks were harvested periodically through the growing season for 4
      yr. Toxic alkaloid concentration [alkaloids containing the N-(methylsuccimimido)
      anthranilik ester group] was determined by Fourier transform infrared (FTIR)
      spectroscopy. Individual larkspur plants varied in alkaloid concentrations,
      especially in early growth (14-38 mg/g). As the concentration declined over the
      growing season, variation among plants also declined. There were yearly
      differences in alkaloid concentration among individual plants (P < 0.01) and
      populations (P < 0.001), even after accounting for differences in phenological
      growth between years. Variables such as precipitation, temperature, days since
      snow melt, growing degree days (sum of mean temperature each day from snow melt),
      and plant height and weight were all considered in a Mallows Cp multiple
      regression selection procedure to predict alkaloid concentration. The mixed model
      procedure in SAS adjusted the regression equation for locations and years.
      Growing degree days was the best single predictor of alkaloid levels: In y =
      (3.581 - 0.00423 GDD), R2 = 0.85. Internal validation of this equation within
      individual years and locations from which the equation was developed, produced
      correlations between observed versus predicted values ranging from r = 0.73 to
      0.93. External validations on nine other larkspur populations produced
      correlations ranging from r = 0.76 to 0.99. This predictive equation can provide
      a tool for ranchers and land managers to make management decisions of when to
      graze cattle in larkspur areas.

PMID- 12523573
TI  - Methyl jasmonate as an allelopathic agent: sagebrush inhibits germination of a
      neighboring tobacco, Nicotiana attenuata.
AB  - Artemisia tridentata ssp. tridentata is the dominant and defining shrub in the
      Great Basin Desert, with well-documented allelopathic tendencies that have
      generally been ascribed to its most abundantly released secondary metabolites.
      However, as a minor component, sagebrush releases a highly biologically active
      substance, methyljasmonate (MeJA), which is known to function as both a
      germination inhibitor and promoter in laboratory studies. Nicotiana attenuata is
      a tobacco species native to the Great Basin Desert and grows in newly burned
      juniper-sagebrush habitats for 2-3 yr following a fire. With a combination of
      field and laboratory studies, we examined the role of MeJA release from sagebrush
      by both air and water transport in inhibiting N. attenuata seed germination. We
      demonstrated that sagebrush interacts allelopathically with the seed bank of N.
      attenuata through its release of MeJA. In the field, seeds buried 0-40 cm from
      sagebrush plants for 4 months in net bags had significantly reduced germination
      compared to seeds buried similarly but protected in plastic bags. Moreover,
      germination on soils collected from underneath sagebrush plants was reduced by
      60% compared to seeds placed on soils collected between sagebrush plants or
      outside of the sagebrush population. Exposure to A. tridentata seeds and
      seedlings did not affect N. attenuata germination, suggesting that established
      sagebrush plants only influence the tobacco's seed bank. In the laboratory,
      exposure of seeds to sagebrush emissions resulted in germination delays of up to
      6 d. Exposure to volatile and aqueous MeJA also inhibited germination of N.
      attenuata seeds at quantities that are released naturally by sagebrush: 3.5
      microg/hr and 1.12 microg/seed cup (56 ng/seed), respectively. A. tridentata
      seeds were significantly more resistant to MeJA, being inhibited at 336 microg
      MeJA (16.8 microg/seed), 300 times greater than the level of aqueous MeJA
      required to inhibit N. attenuata seeds. MeJA inhibited N. attenuata germination
      regardless of the seed's dormancy state and the specific epimer (trans- or cis-)
      of MeJA. Germination on sagebrush chaff that had been heated to reduce MeJA
      content was negatively correlated with the amount of MeJA remaining in the chaff.
      Germination of a nondormant, conspecific tobacco, N. trigonophylla, which grows
      in the same area but is not associated with fire, is less sensitive than N.
      attenuata to the extracts of sagebrush litter, but similarly sensitive to MeJA.
      Additionally, four of five other tobacco species that are not known to be
      associated with sagebrush are less sensitive to MeJA, suggesting an evolved
      sensitivity to MeJA. To determine the proportion of germination inhibition of a
      sagebrush extract that could be attributed to MeJA, we serially diluted sagebrush
      extracts with water and restored the quantity of MeJA of the original extract by
      adding appropriate quantities of synthetic MeJA; 16-60% of the inhibitory
      activity of the original extract could be attributed to the MeJA. We conclude
      that MeJA release from sagebrush plays an allelopathic role for N. attenuata seed
      banks, but other unidentified compounds are also involved.

PMID- 12523574
TI  - Odorant binding protein homologues of the malaria mosquito Anopheles gambiae;
      possible orthologues of the OS-E and OS-F OBPs OF Drosophila melanogaster.
AB  - Twenty-nine Anopheles gambiae candidate Odorant Binding Proteins (OBPs) were
      characterized for similarity to OBPs of Drosophila melanogaster and other
      insects. Twenty-five of these sequences were identified by BLAST searching the A.
      gambiae genome database. Several A. gambiae sequences were significantly similar
      to the D. melanogaster OBPs OS-E/OS-F, LUSH and PBPRP2/PBPRP5. Exon boundary
      comparisons suggests that two A. gambiae genes are orthologues of OS-E and OS-F,
      justifying the names AgamOS-E (EAA0 1090, AF437886) and AgamOS-F (EAA14641,
      AF437884). If these are orthologues. then the gene duplication establishing the
      OS-E and OS-F lineages predated the divergence of mosquitoes and flies. The
      identification of orthologous OBPs and other chemosensory genes between D.
      melanogaster and A. gambiae should accelerate the transfer of physiological and
      behavioral information between these two species.

PMID- 12523575
TI  - Umbilical cord blood transplantation: where do we stand?
AB  - Although allogeneic stem cell transplantation can cure patients with hematologic
      malignancies, limiting factors such as lack of suitable donors and GVHD toxicity
      have led to the exploration of umbilical cord blood (UCB) as an alternative
      source of hematopoietic stem cells. This overview examines the advantages and
      disadvantages of UCB as a donor source and reviews data from preclinical and
      clinical studies. Ethical issues regarding UCB transplantation are also
      addressed.

PMID- 12523576
TI  - Chloroquine prevention of murine MHC-disparate acute graft-versus-host disease
      correlates with inhibition of splenic response to CpG oligodeoxynucleotides and
      alterations in T-cell cytokine production.
AB  - The 4-aminoquinolines, chloroquine and hydroxychloroquine, are established, with
      a 52% response rate, as therapy for human steroid-refractory GVHD after BMT.
      Chloroquine affects numerous mechanisms that play a role in GVHD, including
      inhibition of major histocompatibility complex (MHC) class II antigen
      presentation, cytokine production, and antigen-presenting cell activation by
      bacterially derived CpG oligodeoxynucleotides (ODNs). Using an MHC-disparate
      murine model, we evaluated the effect of chloroquine treatment on the development
      of acute GVHD. We assessed the effect of chloroquine on the immunostimulatory
      responses induced by CpG ODNs after BMT. We also evaluated the impact of
      chloroquine on cytokine-producing populations known to affect GVHD, including
      CD4+ and CD8+ T-cell and CD3(+)/NK1.1(+) natural killer T-cell (NKT cell)
      populations. Twelve (86%) of 14 mice receiving phosphate-buffered saline solution
      (PBS) developed lethal GVHD; only 4 (29%) of 14 mice receiving chloroquine 20
      mg/kg 3 times per week developed lethal GVHD (P < .01). Chloroquine significantly
      suppressed CpG ODN-induced splenic proliferation and interleukin 6 (IL-6)
      production associated with GVHD. Chloroquine suppressed CD8+ T-cell production of
      IL-2 and IL-4 associated with GVHD in this model and maintained an early
      expansion (day 7) of splenic NKT cells. These results indicate that the 4
      aminoquinolines are effective in therapy for or prevention of acute GVHD
      secondary to MHC disparities. Chloroquine actions may include inhibition of CpG
      ODN augmentation of GVHD. Other mechanisms involved may include suppression of
      CD8+ T-cell production of IL-2 and IL-4 and an increase in NKT cells associated
      with GVHD inhibition by chloroquine.

PMID- 12523577
TI  - Prophylactic antithymocyte globulin reduces the risk of chronic graft-versus-host
      disease in alternative-donor bone marrow transplants.
AB  - We studied the impact of preparative regimens with or without antithymocyte
      globulin (ATG) on chronic GVHD in 160 patients undergoing marrow transplants from
      unrelated donors (n = 127) or partially mismatched related donors (n = 33). A
      conditioning regimen that included rabbit ATG, 7.5 to 15 mg/kg (Thymoglobuline;
      Sangstat, Lyon, France), was given to 102 patients, whereas a conditioning
      regimen without ATG was given to 58 patients. The median patient age was 34 years
      for the ATG group and 29 years for the non-ATG group (P = .002); otherwise the 2
      groups were matched for disease phase, diagnosis, donor age, interval from
      diagnosis to transplantation, and number of cells infused at the time of
      transplant. Median follow-up for surviving patients was 4.5 years (range, l.5-9
      years). The conditioning regimen was cyclophosphamide (CY) and total body
      irradiation (TBI) in 95 patients and CY-thiotepa in 65 patients; the source of
      stem cells was bone marrow for all patients. Acute GVHD grades II-IV and grades
      III-IV were reduced in patients receiving ATG compared to patients not receiving
      ATG (51% versus 74%, P = .004 and 14% versus 28%, P = .03, respectively). There
      were significantly fewer patients with chronic GVHD in the ATG group than in the
      non-ATG group at 6 months (14% versus 30%, P = .03), 1 year (7% versus 41%, P =
      .0001), 2 years (16% versus 36%, P = .02), and 4 years (5% versus 34%, P = .002)
      and beyond 4 years (0% in 19 patients at risk versus 29% in 24 patients at risk,
      P = .01). More patients in the ATG group than in the non-ATG group had a
      performance status (Karnowski score) greater than 90 at last follow-up (93%
      versus 56%, P = .01) and had discontinued cyclosporin treatment 2 years
      posttransplant (28% versus 3%, P = .003). Survival rates were comparable in the
      ATG and non-ATG groups for patients who received TBI (56% versus 59%, P = .7) and
      those who received thiotepa (33% versus 18%, P = .3). Transplant mortality and
      relapse rates were also comparable in the 2 groups for these patients. We
      conclude that pretransplant ATG administration reduces the risk of acute and
      chronic GVHD, improves quality of life, and increases the likelihood that
      discontinuation of immunosuppressive therapy will be possible.

PMID- 12523578
TI  - Oral valacyclovir versus intravenous acyclovir in preventing herpes simplex virus
      infections in autologous stem cell transplant recipients.
AB  - Patients who are seropositive for herpes simplex virus (HSV) and are undergoing
      autologous marrow or peripheral blood stem cell transplantation require
      prophylaxis for HSV infection. Most prophylaxis regimens have used intravenous
      acyclovir (ACY). Oral valacyclovir (VAL), the L-valyl ester of ACY, can be used
      to achieve plasma concentrations equivalent to levels achieved with intravenous
      ACY. In this study, adults undergoing autologous stem cell transplantation were
      randomized to receive ACY, 250 mg/m2 intravenously (IV) every 12 hours from day 0
      to engraftment, or VAL, 1 g orally every 12 hours from day 0 to engraftment. The
      primary study objective was to compare cost of HSV prophylaxis between study
      groups. Thirty patients were randomized to receive either oral VAL (n = 14) or IV
      ACY (n = 16) prophylaxis. Mean pharmacy cost of HSV prophylaxis in the patient
      group randomized to IV ACY was $1080 versus $320 for the group randomized
      initially to VAL. This study demonstrates the feasibility and significant cost
      savings of using oral VAL for HSV prophylaxis.

PMID- 12523579
TI  - High-dose chemotherapy and hematopoietic support for patients with high-risk
      primary breast cancer and involvement of 4 to 9 lymph nodes.
AB  - Despite modern chemotherapy, advanced breast cancer remains a significant cause
      of cancer morbidity and mortality in women. Patients with disease involvement of
      multiple lymph nodes represent a subgroup with a high risk of relapse. In
      particular, 50% of patients with 4 to 9 axillary lymph nodes involved will
      relapse after standard chemotherapy. In an effort to improve the survival of
      patients with 4 to 9 involved nodes, we performed a phase II study in which 61
      patients with surgically diagnosed stage II or III breast cancer and 4 to 9
      positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed
      by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and
      carmustine and infusion of autologous hematopoietic progenitor cells. All
      patients received posttransplantation localized radiotherapy unless
      contraindicated, and all patients with hormone receptor-positive disease received
      tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years),
      the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free
      survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%.
      Interstitial pneumonitis occurred in 69% of patients but did not contribute to
      mortality. Our study presents long-term favorable results regarding the use of
      consolidative HDC with autologous hematopoietic support in previously untreated
      patients with high-risk primary breast cancer.

PMID- 12523580
TI  - Risk factors for moderate-to-severe chronic graft-versus-host disease after
      allogeneic hematopoietic stem cell transplantation.
AB  - Among 810 consecutive hematopoietic stem cell transplantation (HSCT) patients,
      679 survived more than 3 months and were evaluated for chronic GVHD. The aim of
      this study was to find predisposing factors increasing the risk of development of
      moderate-to-severe chronic GVHD. Many of the donors were HLA-identical siblings
      or related (n = 435), 185 were HLA-matched unrelated, and 59 were mismatched
      related or unrelated donors. Most of the patients had a hematological malignancy
      (n = 568), but 111 patients with a nonmalignant disease were included. Two
      hundred twenty-three patients (33%) developed mild, 41 (6%) moderate, and 15
      (2.2%) severe chronic GVHD. The 5-year probability of development of moderate-to
      severe chronic GVHD was 10%. We analyzed 30 potential risk factors for chronic
      GVHD. In the multivariate analysis, acute GVHD) grades II to IV (relative hazard
      [RH], 2.30; 95% CI, 1.29-4.10; P = .005), CML diagnosis (RH, 2.37; CI, 1.38-4.08;
      P = .002) and transplantation from an immunized female donor to a male recipient
      (RH, 2.16; CI, 1.14-4.11; P = .02) were independent risk factors for moderate-to
      severe chronic GVHD. Recipient age also was significant (RH, 2.42; CI, 1.23-4.77;
      P = .01) if CML was not included in the analysis. In patients with no risk
      factors, the 5-year probability of development of moderate-to-severe chronic GVHD
      was 5%. In patients with 1 risk factor, the probability was 13%; 2 risk factors,
      23%; and 3 risk factors, 45%. Among patients who developed chronic GVHD (n =
      279), acute GVHD grades II to IV (RH, 2.18; CI, 1.23-3.86; P < .01) was the only
      predictive factor for moderate-to-severe chronic GVHD versus mild disease.
      Patients with previous acute GVHD grades II to IV may benefit from more
      aggressive initial treatment. This possibility would have to be examined in
      clinical trials.

PMID- 12523581
TI  - Functional dyspepsia and gastric acid: any relation?

PMID- 12523582
TI  - Acute pancreatitis-associated lung injury: pathophysiological mechanisms and
      potential future therapies.

PMID- 12523583
TI  - Incidence and survival trends of esophageal carcinoma in the United States:
      racial and gender differences by histological type.
AB  - BACKGROUND: The incidence of esophageal adenocarcinoma in White males has been
      reported to be increasing. The aims of this study were to determine: 1) the
      incidence trends of esophageal carcinoma in the United States with an emphasis on
      histologic type, sex, and ethnicity, 2) whether the reported increase in stage IV
      tumors can be confirmed, and 3) survival trends and factors affecting survival.
      METHODS: Data from the SEER program of the National Cancer Institute with
      submission dates 1973-98 were used. Data on Hispanics were available for analysis
      only for the years 1992-98. Statistical analysis was performed utilizing
      SEER*Stat and SAS statistical software packages. RESULTS: The incidence of
      adenocarcinoma in White males is still rising (7.8%/year, P < 0.0001); however,
      the same trend was observed for White females (6.48%/year; P < 0.0001). Hispanic
      males (3.91 %/year; P < 0.02), and Hispanic females (9.4%/ year; P < 0.04). The
      incidence of squamous cell carcinoma has been steadily declining in White males
      and females and in Black females since 1973, with the incidence showing a
      dramatic and significant decline in Black males beginning in 1992 (8.53%/year; P
      = 0.0009). Stage 4 carcinoma is declining in incidence. Survival of patients with
      esophageal carcinomas has been improving. In a Cox multivariate model,
      independent prognostic factors in esophageal carcinoma included tumor stage,
      tumor type, gender, race, age at diagnosis, and year of diagnosis. CONCLUSIONS:
      1) The incidence of adenocarcinoma continues to rise in White males and females,
      but also in Hispanics, while squamous cell carcinoma is declining; 2) the
      incidence of stage 4 carcinomas has been declining, and 3) survival has been
      steadily improving, independently of all other risk factors.

PMID- 12523584
TI  - Heat-shock preconditioning affects restitution of isolated guinea pig gastric
      mucosa by an arachidonic acid and protein synthesis dependent mechanism.
AB  - BACKGROUND: Superficial mucosal injury is repaired immediately by a process known
      as restitution, which is controlled by several factors and is based on cellular
      migration. Heat-shock preconditioning increases the tolerance of tissue to deep
      gastric mucosal injury via synthesis of heat-shock proteins. Despite immediate
      positive effects on the tissue, we have shown that heat-shock preconditioning
      inhibits restitution of gastric mucosa after subsequent superficial injury in
      correlation with Hsp70 levels. In addition to heat-shock proteins, heat
      preconditioning is known to affect eicosanoid pathways. In this study, we explore
      the role of eicosanoid pathways and protein synthesis in heat-shock-induced
      inhibition of restitution. METHODS: Guinea pig gastric mucosa was mounted and
      perfused in a Ussing chamber (37 degrees C). After heat-shock preconditioning
      (HS) (42 degrees C) and normothermic recovery, a superficial injury was induced
      (1.25 mol/L NaCl) followed by a 3-h restitution. Transmucosal electrophysiologic
      resistance of the tissue (R) was recorded during the experiment. During
      perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid as a
      substrate for eicosanoid pathways; 50 micromol/L quercetin to inhibit the
      metabolism of arachidonic acid via lipoxygenases, 50 micromol/L indomethacin to
      inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or 150
      micromol/L cycloheximide to inhibit de novo protein synthesis. After the
      experiment, the mucosa was prepared for morphologic analysis and Western
      blotting. RESULTS: HS inhibited restitution after NaCl insult and upregulated
      Hsp70. Exposure of the tissue to quercetin, cycloheximide, arachidonic acid, or
      to indomethacin overcame the inhibitory effect of HS, which could be pronounced
      by simultaneous indomethacin and quercetin augmenting expression of Hsp70.
      CONCLUSION: HS preconditioning inhibits restitution by a mechanism that involves
      arachidonic acid metabolism and de novo protein synthesis.

PMID- 12523585
TI  - Comparison of three triple regimens with omeprazole or ranitidine bismuth citrate
      for Helicobacter pylori eradication.
AB  - BACKGROUND: Regimens with ranitidine bismuth citrate (RBC) or omeprazole (O) are
      effective in eradicating Helicobacter pylori. This randomized, open, multicentre
      trial compares three different regimens with these drugs. METHODS: Consecutive H.
      pylori +ve outpatients were included. The alternative regimens were: 1) O 20 mg,
      clarithromycin (C) 250 mg and metronidazole (M) 500 mg (O.C.M), 2) RBC 400 mg, C
      250 mg and M 500 mg (RBC.C.M), 3) RBC 400 mg, tetracycline (T) 1000 mg and M 500
      mg [RBC.T.M]. All drugs were given twice daily for 7 days. H. pylori infection
      was assessed with H. pylori urea breath tests. RESULTS: 426 H. pylori +ve
      patients were included (mean age 58 years [range 18-88], male/female: 244/182).
      The eradication rates (intention to treat) in the O.C.M, RBC.C.M and RBC.T.M
      groups were 117/137 (85%), 141/146 (97%) and 117/143 (82%), respectively (P <
      0.001, overall assessment). There were no significant differences in side effects
      between the alternatives. CONCLUSION: In this trial, RBC.C.M was the most
      effective one, it was well tolerated and compliance was satisfactory. RBC.T.M is
      an alternative to regimens with clarithromycin.

PMID- 12523586
TI  - Bovine anti-Helicobacter pylori antibodies for oral immunotherapy.
AB  - BACKGROUND: Passive immunization with orally administered antibodies against
      specific pathogens has previously been successfully used therapeutically in both
      animal and human studies. We employed a similar strategy for experimental
      treatment of mice infected with the gastric pathogen Helicobacter pylori.
      METHODS: An anti-H. pylori bovine colostral hyperimmune immunoglobulin
      preparation (BIC) was generated and its efficacy was tested in different in vitro
      experiments, such as binding to the Lewis(b) blood group antigen, inhibition of
      adherence of H. pylori to human gastric mucosa tissue sections in situ and in a
      haemagglutination assay. The BIC preparation was also given in the drinking water
      to H. pylori-infected mice. RESULTS: An inhibition of 95% of the binding of H.
      pylori to Lewis(b) glycoconjugate was observed in vitro. Furthermore, a blocking
      activity of almost 90% was observed when the BIC was preincubated with H. pylori
      bacteria. Finally, the BIC preparation inhibited the haemagglutination of H.
      pylori and human red blood cells. Seven of 40 (17.5%) mice remained infected in
      the treatment group as compared with 25 of 45 (55.5%) in the control group.
      Hence, the cure rate was 66%, P = < 0.001. The mean number of colonies in the
      antibody-treated mice where eradication was not successful was also reduced (P <
      0.05). In trials using FVB/N transgenic Lewis(b) expressing mice, a cure rate of
      50%-66% was observed. CONCLUSION: Bovine colostral antibodies against H. pylori
      can be generated in high titres, inhibit binding in vitro and can eradicate or
      reduce the number of bacteria in infected mice.

PMID- 12523587
TI  - Patients with endoscopic gastritis and/or duodenitis improve markedly following
      eradication of Helicobacter pylori, although less so than patients with ulcers.
AB  - BACKGROUND: It is well documented that dyspepsia in patients with peptic ulcer
      disease (PUD) improves markedly after eradication of Helicobacter pylori, while
      rarely does it improve in patients with functional dyspepsia. There is a large
      group of H. pylori-infected patients who do not qualify for either diagnosis, but
      in whom eradication may be considered. The aim of this study was to compare
      symptom severity, change in gastrointestinal symptoms 1 year after eradication
      and satisfaction with therapy between PUD patients and patients with endoscopic
      diagnoses of gastritis and/or duodenitis (G/D patients). METHODS: The patients
      were randomized to one of four triple regimens containing ranitidine bismuth and
      metronidazole, and either oxytetracycline or spiramycine. Eradication was
      assessed with the 14C-urea breath test. GI symptoms were evaluated using the
      Gastrointestinal Symptom Rating Scale (GSRS) and the Ulcer Esophagitis Subjective
      Symptoms Scale (UESS) questionnaires. RESULTS: One-hundred-and-eighty-three
      patients were recruited from GI outpatient clinics. Patients with PUD and G/D had
      similar severity of symptoms before eradication therapy. One year after H. pylori
      eradication, 99% of the PUD patients and 75% of the G/D patients felt better
      regarding their main upper GI complaint. Abdominal pain score decreased by 48% as
      measured by GSRS and by 78% as measured by UESS in the PUD group and by 25% and
      47%, respectively, in the G/D group. Reflux symptoms decreased by 41% and 63% in
      PUD patients and by 28% and 45% in G/D patients; indigestion by 30% and 47% in
      PUD and by 20% and 34% in G/D; eating discomfort by 60% in PUD and by 35% in G/D.
      Sleep quality score improved by 68% in PUD and by 41% in NU patients.
      Constipation decreased by 22% in the PUD group. All these differences in symptoms
      were highly significant compared to baseline. Diarrhoea was unchanged.
      CONCLUSIONS: Abdominal pain, reflux symptoms, indigestion and the ability to eat
      and sleep improved in both PUD and G/D patients 1 year after H. pylori
      eradication. Chronic diarrhoea was not induced. Abdominal pain improved
      significantly more in PUD than in G/D patients. Further study of the effect of
      H.pylori eradication in G/D patients is warranted.

PMID- 12523589
TI  - Impaired accommodation of proximal stomach in patients with alcoholic liver
      cirrhosis.
AB  - BACKGROUND: Impaired gastric emptying has previously been detected by
      ultrasonography in cirrhotic patients, and the role of the type of meal has also
      been discussed. While these earlier studies dealt with the distal part of the
      stomach, the aim of our study was to examine the effects of three different types
      of meal on the proximal stomach in cirrhotic patients. METHODS: The proximal
      stomach was examined by ultrasonography in 15 healthy volunteers and in 21
      alcoholic cirrhotic patients. The subjects received a liquid meal with a low
      calorie content and two different semisolid test meals with a low calorie content
      or high calorie and fat contents. The proximal gastric size was assessed by
      ultrasonography in a sagittal area and a frontal diameter. On the basis of
      assessment of the autonomic nervous function, the cirrhotic patients were divided
      into two groups: autonomic neuropathy positive and autonomic neuropathy negative.
      RESULTS: The postcibal gastric size immediately after ingestion of the liquid
      test meal was significantly lower in the cirrhotic patients than in the healthy
      controls. In the healthy volunteers, the measures of the proximal gastric size
      were significantly higher than in either group of cirrhotic patients at to, and
      at 10, 20 or 30 min after ingestion of a semisolid test meal with low calorie and
      fat contents. The proximal gastric sizes in the three groups of investigated
      subjects did not differ when the meal with high fat and calorie contents was
      tested. When the liquid meal was administered, the proximal gastric size was
      significantly lower in the cirrhotic patients with autonomic neuropathy. A
      significant intragroup difference was not observed when the semisolid meals were
      tested. CONCLUSIONS: This study reveals an impairment of the proximal stomach in
      alcoholic cirrhotic patients. The low calorie liquid meal distinguishes between
      the two groups of cirrhotic patients and healthy controls.

PMID- 12523590
TI  - Does water-perfused catheter overdiagnose anismus compared to balloon probe?
AB  - BACKGROUND: The purpose of this study was to compare the manometric assessment of
      straining effort as if to defecate and rectoanal inhibitory reflex obtained with
      a rectosphincteric balloon probe and with a water-perfused catheter in the same
      subject. METHODS: Twelve healthy volunteers underwent two manometric assessments
      of anal sphincter function and electromyographic (EMG) surface recordings. one
      with a rectosphincteric balloon and one with a water-perfused catheter, 7 days
      apart in random order. RESULTS: Increased EMG activity in the external anal
      sphincter in the midst of the rectoanal inhibitory reflex (P < 0.001) and during
      straining for defecation (P < 0.001) was more frequently observed with the
      perfused system than with the balloon probe. There was a discrepancy between the
      EMG activity of the external anal sphincter and the anal pressures during
      straining recorded with the perfused system. Duration of the reflex elicited by
      rectal distension with 10 and 20 ml of air was significantly greater with the
      rectosphincteric balloon than with the perfused catheter (P = 0.02 and P = 0.05,
      respectively). CONCLUSION: Water instilled in the anal canal by the perfused
      system induces artifacts in EMG recording and active anal contractions. These
      artifacts and induced contractions could lead to an erroneous diagnosis of
      anismus, particularly if pelvic floor EMG is only taken into account for the
      diagnosis of anismus.

PMID- 12523591
TI  - Effect of inositol-trisphosphate on fluid transport and protein extravasation in
      the obstructed small bowel.
AB  - BACKGROUND: Small-bowel obstruction is characterized by accumulation of fluid in
      the obstructed intestine. A pronounced inflammation in the obstructed gut wall
      has been shown to play an important role in the pathogenesis of the profuse fluid
      losses. alpha-Trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) has potent
      anti-inflammatory as well as antisecretory properties. The effects of alpha
      Trinositol on inflammation and fluid losses in the obstructed small intestine are
      examined. METHODS: A total obstruction of the proximal part of the rat jejunum
      was induced during 18 h by thread ligation. A small segment of the obstructed
      intestine, with intact vascular and nervous supply, was placed in a chamber
      suspended from a force displacement transducer allowing for continuous
      registration of net fluid transport on a Grass polygraph. Three groups were
      included. One group (n = 12) received low-dose alpha-Trinositol (bolus: 2 mg kg(
      1); IV infusion: 10 mg kg(-1) min(-1)), a second group (n = 10) received high
      dose alpha-Trinositol (bolus: 12 mg kg(-1); IV infusion: 60 mg kg(-1) min(-1)),
      while a control group (n = 9) received corresponding volumes of isotonic saline
      (bolus: 0.5 ml; IV infusions 15 microl min(-1)). Quantitative measurement of
      extra-vasated Evans blue albumin in the obstructed jejunum was used as a marker
      of inflammation. RESULTS: High-dose alpha-Trinositol induced a significant (P <
      0.001) inhibition of net fluid secretion, while low-dose alpha-Trinositol had no
      significant effect versus saline. In contrast, both doses of alpha-Trinositol
      induced significant inhibition of EB-albumin leakage (P < 0.05). CONCLUSION: High
      dose alpha-Trinositol is a potent inhibitor of fluid secretion in obstructive
      ileus, most probably involving an anti-inflammatory mechanism.

PMID- 12523588
TI  - Effect of profound acid suppression in functional dyspepsia: a double-blind,
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent
      pain/discomfort centred in the upper abdomen, where no structural explanation for
      the symptoms is found. The role of drug treatment remains controversial. The aim
      in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d)
      and to test methods for symptom assessment. METHODS: 197 patients fulfilling the
      criteria for FD were randomly allocated to double-blind treatment with omeprazole
      20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known
      gastrointestinal disorder or with main symptoms indicating gastro-oesophageal
      reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori
      testing and 24-h intra-oesophageal 24-h pH-metry were performed before
      randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS:
      A stringent endpoint, 'complete symptom relief on the last day of treatment', was
      the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and
      17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): 
      0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%,
      respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit
      of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no
      dyspeptic symptoms on the last 2 days of treatment and overall treatment
      response. H. pylori status and the level of oesophageal acid exposure did not
      significantly influence the response to therapy. CONCLUSION: A subset of patients
      with FD will respond to therapy with omeprazole.

PMID- 12523592
TI  - Low serum concentrations of insulin-like growth factor-I in children with active
      Crohn disease: effect of enteral nutritional support and glutamine
      supplementation.
AB  - Dept. of Paediatric Gastroenterology, Central Manchester Hospital, Manchester,
      UK.

PMID- 12523593
TI  - Cyclooxygenase-2 inhibition and experimental colitis: beneficial effects of
      phosphorothioated antisense oligonucleotide and meloxicam.
AB  - BACKGROUND: The effects of cyclooxygenase-2 (cox-2) inhibition by a cox-2
      selective antisense phosphorothioated oligonucleotide (AS) and meloxicam were
      examined in experimental colitis. METHODS: Colitis was induced by
      trinitrobenzenesulphonic acid (TNBS) and acetic acid (Hac) separately in male
      Sprague-Dawley rats. Both groups of animals were treated daily intraperitoneally
      with AS and a mismatched control oligo (CO) (3 mg/kg), and orally with meloxicam
      (7.5 mg/kg) 1 h before induction of colitis. The animals were killed on day 4
      (Hac) and on day 5 (TNBS). Tissue samples from colon, ileum, liver, kidney and
      spleen were collected for mRNA, myeloperoxidase activity (MPO), prostaglandin E2
      (PGE2) estimation and for histology, and blood samples for PGE2, thromboxane B2
      (TxB2) and TNF-alpha. RESULTS: Both TNBS and Hac increased colonic MPO activity,
      PGE2 concentrations and infiltration of colonic wall by inflammatory cells. Serum
      levels of TNF-alpha were increased in both models, whereas PGE2 was increased
      only in TNBS colitis. Only meloxicam suppressed the level of PGE2 significantly
      below the basal level. The animals in both models also showed splenomegaly. The
      colitis-induced changes were significantly suppressed by the treatment of the
      test compounds but not by the CO. Cox-2 mRNA but not cox-1 was decreased by the
      AS, but not by meloxicam or in CO-treated colitic animals. CONCLUSION: The
      findings demonstrate comparable beneficial effects of the cox-2 selective
      antisense oligonucleotide and meloxicam, which seem to be mediated by a combined
      inhibition of both PGE2 and TNF-alpha in the present models of colitis.

PMID- 12523594
TI  - Delay of diagnosis in pancreatic cancer due to suspected symptomatic
      cholelithiasis.
AB  - BACKGROUND: A single centre study was conducted to examine the frequency of
      cholecystectomies, both open and laparoscopic, up to 2 years prior to the
      diagnosis of pancreatic cancer. In particular, it was of interest to investigate
      whether there is a diagnostic delay in a significant number of pancreatic cancer
      patients and if these patients already have symptoms or findings at the time of
      cholecystectomy that might have been indicative of the underlying malignant
      disease. METHODS: It is demonstrated that 17 out of 186 pancreatic cancer
      patients (9%) underwent a cholecystectomy within the 2 years prior to cancer
      diagnosis. RESULTS: A significant number of these patients showed a considerable
      weight loss at the time of the cholecystectomy. It is hypothesized that symptoms
      which led to cholecystectomies in these patients were most likely related to the
      pancreatic cancer. Owing to the resulting delay of pancreatic cancer diagnosis
      the resection rate with curative intent decreases to 35% from 44% in the whole
      series. CONCLUSION: Patients suffering from cholecystolithiasis and showing
      atypical symptoms or other notable findings such as considerable weight loss
      might be assessed in more detail pre- as well as postoperatively in order to
      minimize the diagnostic delay in pancreatic cancer and to avoid unnecessary
      operations.

PMID- 12523595
TI  - Expression of p33(ING1) in hepatocellular carcinoma: relationships to tumour
      differentiation and cyclin E kinase activity.
AB  - BACKGROUND: Inhibitor of growth-1 (ING1) is a new candidate for the tumour
      suppressor gene that encodes a 33k Da protein (p33(ING1)). While reduction of
      p33(ING1) is an important event in some human cancers, the expression of
      p33(ING1) in human hepatocellular carcinoma (HCC) remains to be examined. We
      evaluated p33(ING1) expression in various liver diseases including HCC. METHODS:
      Expression of p33(ING1) was evaluated immunohistochemically not only in the
      normal liver (n = 5), but also in specimens of chronic hepatitis (n = 39) and HCC
      (n = 86). We also analysed the relationship between p33(ING1) expression and
      cyclin E kinase activity detected by autoradiography in 29 HCCs. RESULTS:
      Expression of p33(ING1) was reduced in HCC, especially in moderately and poorly
      differentiated HCCs, and those at advanced stages. Furthermore, expression of
      p33(ING1) correlated inversely with cyclin E kinase activity. CONCLUSIONS: These
      data suggest that reduction of p33(ING1) may contribute to the process of
      malignant transformation, progression and dedifferentiation of HCC via an
      increase of cyclin E kinase activity.

PMID- 12523596
TI  - Outcome of necrosectomy in acute pancreatitis: the case for continued vigilance.
AB  - BACKGROUND: Surgery for pancreatic necrosis complicating acute severe
      pancreatitis carries a high risk of mortality and may be influenced by a range of
      variables including patterns of referral, case selection and quality of care.
      METHODS: An observational study of a consecutive series of 54 patients undergoing
      pancreatic necrosectomy in a specialist Hepatobiliary unit over an 8-year study
      period. Principal outcomes were organ dysfunction and physiological derangement
      in relation to surgery, microbial colonization of necrosis and relation to
      outcome, re-operation rates, requirement for peri-operative nutritional support,
      trends in mortality and survival analysis. RESULTS: Necrosectomy was associated
      with statistically significant deterioration in immediate postoperative organ
      dysfunction scores (ANOVA P < 0.01). Infected necrosis was present in 36 (68%).
      Fungal colonization of necrosis was present in 5 (9%). Mortality in this subgroup
      was 80% (4 deaths). There was no association between bacterial colonization of
      necrosis and death in this study (P = 0.77; Fisher exact test; relative risk
      0.9,95% confidence interval 0.54-1.54). Twenty patients (37%) required further
      surgical intervention with an average of 1.5 surgical procedures per patient.
      Twenty-three patients (43%) died. Patient survival to discharge was best
      predicted by admission APACHE-II score with relative risk of death increasing 14%
      for each unit increase in APACHE-II score at admission. CONCLUSIONS: The results
      of the present study illustrate that there is no place for complacency in the
      surgical management of patients with severe acute pancreatitis. A clinical
      governance approach would promote pre-defined protocols between admitting
      hospitals and tertiary referral centres. Future research should target new
      interventions in patients with high admission APACHE-II scores in whom prognosis
      is particularly poor and explore the role of infection of necrotic tissue.

PMID- 12523597
TI  - Resection of the head of the pancreas in Finland: effects of hospital and surgeon
      on short-term and long-term results.
AB  - BACKGROUND: To study the effect of hospital volume and surgeon volume on
      postoperative hospital mortality, morbidity and long-term survival after
      resection of the head of the pancreas in a nationwide study (case record study),
      taking into a consideration risk factors found important in series based on
      experience in one hospital. METHOD: The case record investigation of 374 patients
      identified from the National Hospital Discharge Database as having undergone
      resection of the head of the pancreas between 1990 and 1994 in Finland. RESULTS:
      The records of 350 patients were obtained for analysis. Operations were performed
      in 33 hospitals by 98 surgeons (average 2.1/year/hospital and 0.7/year/surgeon).
      Hospital mortality was 36/350 (10%), increasing from 4 and 7 to 13% with
      decreasing hospital volume from > 10 and 5-10 to < 5 respectively (P < 0.05) and
      increasing from 3 and 10 to 14% with decreasing surgeon volume from > 3 and 1-3
      to < 1, respectively (P < 0.05). Most deaths were caused by surgical or technical
      complications (31/36 = 86%). Besides hospital mortality, postoperative
      complications, re-operations and hospital stay were also affected by surgeon
      volume. In the univariate analysis, also the age of the patient had an effect on
      the hospital mortality, and preoperative biliary stenting on the uncomplicated
      recovery, but in the multivariate analysis hospital mortality was independently
      affected by age (OR 0.94, P = 0.004) and surgeon volume (OR 1.3, P = 0.04), re
      operations by surgeon volume (OR 1.10, P = 0.05) and hospital volume (OR 1.03, P
      = 0.05), postoperative complications by using the preoperative stent (OR 0.45, P
      = 0.02). Long-term survival was dependent on the histology of the specimen and by
      uncomplicated recovery, but not by hospital volume or surgeon volume. CONCLUSION:
      To decrease postoperative morbidity, mortality and hospital stay, pancreatic head
      surgery needs to be concentrated to only a few hospitals and to a few surgeons.

PMID- 12523598
TI  - Secular trends in incidence and 30-day case fatality of acute pancreatitis in
      North Jutland County, Denmark: a register-based study from 1981-2000.
AB  - BACKGROUND: The incidence rate of acute pancreatitis has been reported as having
      increased during recent decades in Western countries. Reported mortality lies
      around 10% and has improved during the past 20 years. The incidence rate and 30
      day case fatality rate of acute pancreatitis in North Jutland County, Denmark
      were examined for the period 1981 to 2000. METHODS: Data were collected from the
      Hospital Discharge Registry of North Jutland County for the period 1981-2000. Sex
      and age-standardized incidence rates and 30-day case fatality rate of a first
      attack of acute pancreatitis were calculated. Data on endoscopic procedures were
      assessed for the period 1992 to 2000 and on certain drugs for 1991 to 1999.
      RESULTS: The incidence rate of acute pancreatitis in women increased from 17.1
      per 100,000 person-years in 1981 (95% confidence interval (CI), 12.6-23.2) to
      37.8 per 100,000 person-years in 2000 (95% CI, 31.0-46.1). The corresponding
      increase in men was from 18 per 100,000 person-years in 1981 (95% CI, 13.3-24.2)
      to 27.1 per 100,000 person-years in 2000 (95% CI, 21.5-34.3). The incidence rate
      of acute pancreatitis increased with age in both sexes. The overall 30-day case
      fatality rate was 7.5% (95% CI, 6.5-8.7) increasing with age, adjusted odds ratio
      (OR) = 6.4 (95% CI, 3.5-11.6) and decreased with time, adjusted OR = 0.7 (95% CI,
      0.4-1.0). CONCLUSION: The incidence of acute pancreatitis has increased, and in
      women surpassed that in men in 1999 and 2000. Short-term prognosis has improved.

PMID- 12523599
TI  - Collaboration by use of the Internet yields data of high quality and detects non
      uniform management of patients with Helicobacter pylori infection.
AB  - BACKGROUND: The benefits of new technology steadily being introduced in medicine
      should be documented. In this study, remote entry of a set of data from the daily
      routine was submitted via the Internet to a common database. The usefulness and
      quality of the information are evaluated. METHODS: Fourteen hospitals reported a
      common data set on consecutive Hp+ve patients handled in accordance with daily
      practice. Participants submitted their data via the Internet to a database. There
      was no monitoring or other surveillance. No audit was planned or expected, but
      was nevertheless possible. Doctor compliance with the common agreement was
      checked, differences in medical practice were noted and quality was assessed
      comparing the most important source data with the data in the final database.
      RESULTS: Four-hundred-and-forty patients were included. The quality of the
      reported data was high, only 1.3% showing a discrepancy between source data and
      the database. Overall treatment success was 89%, with no significant differences
      between hospitals. There were significant differences in clinical practice
      between the centres, the proportion of patients treated for ulcer disease varying
      from 36% to 96% (P < 0.001). Doctor compliance with the agreed collaboration
      varied significantly (P < 0.001). CONCLUSION: Internet collaboration through
      remote data entry in a common database yields data of high quality without
      monitoring, and is a powerful and resource economic tool for clinical multicentre
      trials and quality assurance.

PMID- 12523600
TI  - Attitudes of elderly patients to examinations and treatments of gastrointestinal
      symptoms.

PMID- 12523601
TI  - Liver metastasis as a first sign of fallopian tube carcinoma and the role of
      positron emission tomography in preoperative diagnosis.
AB  - The search for an unknown primary tumour is often time-consuming, costly and
      unrewarding. Positron emission tomography might be an effective method for
      screening the body for malignant deposits. We present the case of a woman with a
      symptomatic liver tumour of unknown origin. Several investigations did not reveal
      a primary tumour, but PET scanning showed a hot spot in the pelvis, suggesting
      either a primary tumour or a metastatic deposit. During operation, a primary
      Fallopian tube carcinoma was detected. Histopathological examination of the
      resected liver tumour revealed a metastasis of the Fallopian tube carcinoma. This
      case report demonstrates that PET scanning can be useful in the diagnostic
      process in patients with unknown primary tumour, and that a symptomatic liver
      tumour can be the first sign of Fallopian tube carcinoma.

PMID- 12523602
TI  - Intestinal metaplasia, high-grade epithelial dysplasia and gastric cancer.

PMID- 12523603
TI  - At long last, a CPT change for obstetric sonography.

PMID- 12523604
TI  - Tissue harmonic imaging of thyroid nodules: initial experience.
AB  - OBJECTIVE: To determine the impact of tissue harmonic imaging on visualization of
      the thyroid and gray scale contrast between thyroid nodules and adjacent thyroid
      parenchyma. METHODS: A prospective study was performed on 144 patients (148
      lesions) undergoing sonographically guided fine-needle biopsy. The fundamental
      frequency and tissue harmonic images were obtained on a scanner with a wideband
      7.5-MHz linear probe. One hundred forty-two benign nodules, 2 papillary
      carcinomas, 1 anaplastic carcinoma, and 1 metastatic lesion were found. In 1 case
      a suggestion of a follicular carcinoma was raised, and in 1 case no diagnostic
      material was obtained. The gray scale intensity of the lesions and adjacent
      thyroid tissue was measured with graphics software, and the gray scale contrast
      between lesions and adjacent thyroid tissue was calculated. Additionally, the
      overall conspicuity and border definition were evaluated by 2 independent
      observers. RESULTS: Tissue harmonic imaging improved the gray scale contrast
      between thyroid nodules and adjacent thyroid parenchyma in 116 lesions (78.4%).
      The overall conspicuity and border definition were improved or equal in the
      harmonic mode for most lesions. CONCLUSIONS: The tissue harmonic imaging
      technique used as an adjunct to conventional thyroid sonography may improve
      lesion detectability and characterization.

PMID- 12523605
TI  - Minimal pelvic fluid in asymptomatic children: the value of the sonographic
      finding.
AB  - OBJECTIVE: To determine the presence of minimal pelvic fluid in asymptomatic
      children who underwent abdominal sonography. METHODS: Between August 1999 and
      January 2001, we performed abdominal sonography in 396 asymptomatic children and
      266 symptomatic children (acute and chronic abdominal pain). The 2 groups were
      evaluated for the presence of minimal fluid in the pelvis. All the children were
      divided into 4 subgroups according to age and sex. RESULTS: Minimal pelvic fluid
      was noted in 28 (7%) of the asymptomatic children, and it was more common in
      girls (10.2%), especially in girls between the ages of 5 and 15 years. On the
      contrary, no difference between the age groups was seen in boys. Minimal pelvic
      fluid was found in 76 (28.6%) of the symptomatic children, with no difference
      seen between the sexes or age groups. The presence of pelvic fluid was
      significantly greater in the symptomatic group than in asymptomatic group (P <
      .001). CONCLUSIONS: Our data suggest that the presence of minimal pelvic fluid in
      children of all ages and both sexes is a physiologic finding and should be
      evaluated in the appropriate clinical context.

PMID- 12523606
TI  - The early sonographic appearance of placenta accreta.
AB  - OBJECTIVE: To determine whether any sonographic findings in the first trimester
      predict placenta accreta. METHODS: Patients who had a diagnosis of placenta
      accreta, increta, or percreta by clinical course or pathologic examination of the
      uterus and who had had a sonographic examination at 10 weeks or earlier were
      included in this study. RESULTS: Seven patients met the study criteria. In 6 of
      these, who had had at least 1 previous cesarean delivery, the gestational sac was
      located in the lower uterine segment at the time of the early scan. Two of these
      pregnancies failed shortly after the early scan, and the patients underwent
      dilation and curettage, at which time severe bleeding necessitated a
      hysterectomy. The other 4 continued to term but had sonographic findings typical
      of placenta accreta during subsequent scans. In the seventh patient (who had had
      no previous cesarean deliveries), the gestational sac was located in the uterine
      fundus. CONCLUSIONS: In a patient with a previous cesarean delivery, a sac lying
      in the lower uterine segment on a scan at 10 weeks or earlier suggests the
      possibility of placenta accreta.

PMID- 12523607
TI  - Impaired uterine arterial blood flow in pregnant women with recurrent pregnancy
      loss.
AB  - OBJECTIVE: This study was undertaken to evaluate uterine perfusion, which
      regulates uterine receptivity, in women with recurrent pregnancy loss. METHODS:
      We evaluated the blood flow resistance in the uterine arteries of 104 pregnant
      women at 4 to 5 weeks' gestation by transvaginal pulsed Doppler ultrasonography
      (control group, n = 52; and recurrent pregnancy loss group, n = 52). Blood tests
      for antinuclear and antiphospholipid antibodies were also performed. RESULTS: The
      uterine arterial pulsatility index in the recurrent pregnancy loss group was
      significantly higher than that in the control group. Women with antinuclear or
      antiphospholipid antibodies had an elevated pulsatility index in the uterine
      artery, which is prominent in women with recurrent pregnancy loss. Coagulopathy
      and vascular dysfunction caused by autoantibodies may impair uterine perfusion.
      However, the uterine arterial pulsatility index in the recurrent pregnancy loss
      group was significantly higher than that in the control group even among women
      without antinuclear antibodies or among women without antiphospholipid
      antibodies. This observation strongly suggests that the uterine artery
      pulsatility index may be an independent index for recurrent pregnancy loss.
      CONCLUSIONS: The introduction of pulsed Doppler ultrasonography has provided the
      means for noninvasive evaluation of uterine impedance and may identify patients
      with recurrent pregnancy loss associated with impaired uterine perfusion.

PMID- 12523608
TI  - An 8-center study to evaluate the utility of mid-term genetic sonograms among
      high-risk pregnancies.
AB  - OBJECTIVE: A multicenter study was undertaken to evaluate the diagnostic efficacy
      of a genetic sonogram. METHODS: Eight centers provided data on 176 pregnancies
      complicated by fetal Down syndrome. One hundred thirty-four pregnancies were
      considered high risk because of advanced maternal age (> 35 years), and 42 were
      considered high risk for having "abnormal" triple-screen results (risk > 1:250).
      Each center provided fetal biometric data, information regarding the presence or
      absence of major structural abnormalities, and between 3 and 6 additional
      ultrasonographic markers for trisomy 21. The heterogeneity of our 8 independent
      "sensitivity estimates" was evaluated by Poisson regression, and a single
      combined estimate of the sensitivity was calculated. RESULTS: Of the total 176
      cases of trisomy 21, 125 fetuses (71.0%) had either an abnormal long bone length
      (femur length, humerus length, or both), a major structural abnormality, or a
      Down syndrome marker. The combined diagnostic sensitivity was 71.6%, with a range
      of 63.6% (7 of 11) to 80% (8 of 10). Five centers had sensitivity estimates
      falling between 64% and 76%. The sensitivity of individual markers varied between
      3% (sandal gap) and 46.5% (nuchal skin fold thickness). A condensed regimen of
      nuchal skin fold thickness, femur length, and a standard anatomic survey would
      screen in 56.8% of fetuses with Down syndrome. CONCLUSIONS: This 8-center study
      that included many fetuses with Down syndrome validates the concept that the
      genetic sonogram can be used to better adjust the Down syndrome risk for high
      risk patients.

PMID- 12523609
TI  - Fetal lateral ventricular width: what should be its upper limit? A prospective
      cohort study and reanalysis of the current and previous data.
AB  - OBJECTIVE: The upper limit of the fetal atrial width in normal fetuses is
      debated. This was a prospective cohort evaluation of the lateral ventricular
      width with special regard to the upper limit of its size. METHODS: Measurements
      of fetal atrial ventricular size were obtained by abdominal ultrasonography in
      427 male and female fetuses between 20 and 40 weeks' gestation of normal
      singleton pregnancies. In addition, reanalysis of previous data (8 studies) and
      the current data was performed to produce a pooled mean and SD. RESULTS: The mean
      ventricular width +/- SD was 6.2 +/- 1.2 mm. The ventricular width did not show
      significant modification throughout gestation. Reanalysis of the current and
      previous studies (8216 cases) yielded a pooled mean of 6.4 +/- 1.2. CONCLUSIONS:
      According to the current and previous studies, the upper cutoff of fetal
      ventricular atrium width should be 10 mm. This cutoff represents a range of
      approximately 3 SDs above the pooled mean, corresponding to a 99.74% confidence
      interval.

PMID- 12523610
TI  - Fetal anatomic and functional echocardiography: a 5-year review.
AB  - OBJECTIVE: To assess the concordance of fetal and postnatal echocardiography when
      congenital heart disease is suspected prenatally. METHODS: The perinatology and
      pediatric cardiology ultrasound databases were searched for fetal echocardiograms
      obtained between June 1995 and June 2000. All cases with abnormal fetal
      echocardiographic findings in which postnatal echocardiography was performed were
      included. A perinatologist, pediatric cardiologist, or both interpreted all fetal
      echocardiograms; a pediatric cardiologist interpreted all postnatal
      echocardiograms. The fetal and postnatal echocardiograms were compared for the
      presence of 25 specific components. The kappa statistic was calculated to
      evaluate concordance between fetal and postnatal studies. Positive and negative
      predictive values for fetal studies were calculated under the assumption that the
      postnatal study yielded the correct diagnosis. RESULTS: Sixty-five patients were
      included. Congenital heart disease ranged from an isolated atrial septal defect
      to complex disease. Images adequately showed all 25 components in more than 85%
      of the fetal studies. Concordance between fetal and postnatal echocardiograms was
      excellent (kappa > 0.75) for 20 of the 25 components evaluated. Four of the
      remaining 5 components had fair concordance (kappa = 0.4-0.75) between fetal and
      postnatal studies. Structural abnormalities without excellent concordance
      included partial anomalous pulmonary venous return, secundum atrial septal
      defects, and heart malposition. Concordance between fetal and postnatal right and
      left ventricular function was fair; however, differences may have been due to
      physiologic changes that occurred after birth rather than to inferior diagnostic
      accuracy of fetal echocardiography. CONCLUSIONS: Fetal echocardiography is an
      extremely useful and accurate clinical tool for prenatal and postnatal evaluation
      of congenital heart disease.

PMID- 12523611
TI  - Nasal bone evaluation in fetuses with Down syndrome during the second and third
      trimesters of pregnancy.
AB  - OBJECTIVE: This study examined the use of three-dimensional ultrasonography for
      evaluating the fetal nasal bone, as a sonographic marker of Down syndrome, during
      the second and early third trimesters of pregnancy. METHODS: Forty fetuses,
      including 20 with trisomy 21, were scanned once by three-dimensional
      ultrasonography. A midline sagittal view of the facial profile was used to
      analyze the volume data. Independent examiners reviewed blinded and randomly
      allocated volume data sets for the nasal bone. Interobserver reliability was
      evaluated for the sonographic presence or absence of the nasal bone. Logistic
      regression determined the contribution of this parameter to the presence of Down
      syndrome. RESULTS: Both examiners showed substantial agreement in scoring whether
      the nasal bone was visualized by three-dimensional ultrasonography (P < .001).
      They identified 40% to 45% of fetuses with abnormalities using the absence of the
      nasal bone as a sonographic marker. However, a substantial number of fetuses with
      abnormalities were also found to have a nasal bone present. The nasal bone was
      visualized in 80% to 90% of fetuses without abnormalities. CONCLUSIONS: Three
      dimensional ultrasonography can be used to evaluate the fetal nasal bone with
      substantial interobserver agreement during the second and early third trimesters
      of pregnancy. A nonvisualized nasal bone identified 40% to 45% of fetuses with
      Down syndrome in this study.

PMID- 12523612
TI  - Intracervical sonographic-pathologic correlation: preliminary results.
AB  - OBJECTIVE: To determine whether current-generation endoluminal ultrasonic
      transducer technology could visualize dysplastic and malignant cervical lesions.
      METHODS: Inclusion criteria for patients enlisted in the study were abnormal
      Papanicolaou test results, an abnormality seen at colposcopy, and consent for a
      cone biopsy. In addition, we included 4 women who were undergoing hysterectomy
      but had no evidence of cervical abnormalities at the time of surgery, for a total
      of 28 women. We used a 20-MHz annular array intravascular transducer. We
      correlated all sonographic and pathologic results with regard to being normal or
      abnormal using the Pearson product moment correlation coefficient, and we
      evaluated interobserver variation by having 5 blinded sonologists interpret each
      examination and calculating kappa statistics. RESULTS: We performed intracervical
      sonography on 24 women with abnormal Papanicolaou test results and on 4 women
      without abnormalities. Nineteen of the 24 women with proven disease had abnormal
      sonographic images. Five women with pathologically proven cervical
      intraepithelial neoplasia I had normal sonographic images. Lesions ranged in size
      from 0.3 to 7 mm. Two carcinomas (5 and 7 mm diameter), multiple nabothian cysts,
      cervicitis, and 2 giant cell foreign body reactions were visible on sonography.
      The correlation coefficient for abnormal sonographic and pathologic findings was
      0.87 (P < .005). We obtained a kappa value of 0.75 for interobserver variation.
      CONCLUSIONS: Intracervical sonography was able to visualize dysplastic lesions
      and carcinomas as hypoechoic defects with surrounding echogenic areas of
      glandular cervical mucosa. Lesions were shown with sufficient resolution and
      interobserver variation to suggest that the technique may be clinically
      applicable, particularly for planning surgical therapy. However, design of a
      transducer that can be easily sterilized between examinations, similar to current
      endovaginal probes, would be necessary to make intracervical sonography a
      clinically feasible examination.

PMID- 12523613
TI  - Sonographic imaging of maternal complications of pregnancy.
AB  - OBJECTIVE: To show the role of diagnostic sonography in delineating pathologic
      conditions occurring during and immediately after pregnancy. METHODS: Cases
      illustrative of a broad range of pathologic conditions were collected primarily
      from personal experience in a busy ultrasound clinic serving high-and low-risk
      pregnancies over the past 15 years, with supplemental cases drawn from
      departmental teaching files. Sonography was the primary diagnostic tool, with
      confirmation obtained from other imaging modalities in select instances. RESULTS:
      Cases were organized on an anatomic and time-of-onset basis. For conditions
      occurring during pregnancy, the following anatomic areas are considered: the
      liver and biliary tree, urinary tract, bowel, ovary, and uterus and placenta. For
      postpartum complications, the following conditions are discussed: subfascial and
      bladder flap hematomas, retained products of conception, and ovarian vein
      thrombophlebitis. Although the main imaging modality in these conditions was
      sonography, correlation with computed tomography and magnetic resonance imaging
      was also made in several cases. CONCLUSIONS: A broad variety of conditions can
      affect the pregnant patient, both during and immediately after pregnancy.
      Sonography can show many of these disease processes, with computed tomography and
      magnetic resonance imaging useful selectively as supplementary tools.

PMID- 12523614
TI  - Three-dimensional power Doppler ultrasonography during pregnancy.
AB  - OBJECTIVES: To present the appearance of fetal and placental vascular anatomic
      structures by three-dimensional power Doppler ultrasonography. METHODS: Three
      dimensional multiplanar imaging, surface rendering, and volume rendering were
      combined with power Doppler ultrasonography to show the methods, imaging
      artifacts, and diagnostic potential of this technology during pregnancy. RESULTS:
      Fetuses with normal and abnormal vascular anatomic structures were evaluated by
      three-dimensional power Doppler ultrasonography. The combination of several
      imaging modalities (e.g., three-dimensional multiplanar imaging, surface
      rendering, and volume rendering) with power Doppler ultrasonography is shown.
      CONCLUSIONS: Three-dimensional power Doppler ultrasonography is an important
      adjunctive method that can be used to characterize normal vascular development
      and circulatory anomalies of the fetus.

PMID- 12523615
TI  - Spontaneous thrombosis of hepatic posttraumatic pseudoaneurysms: sonographic and
      computed tomographic features.
AB  - Hepatic artery pseudoaneurysms are rare complications of blunt abdominal trauma.
      In the past, surgical ligation was the recommended treatment; today, it is
      embolization. We report a case of a child involved in a motor vehicle collision
      who had liver lacerations with subsequent development of hepatic artery
      pseudoaneurysms. In this case, embolization was not performed, and the
      pseudoaneurysms regressed spontaneously. Spontaneous regression has been reported
      previously, but its true prevalence is unknown. Our report includes full
      sonographic and partial computed tomographic (CT) documentation of the lesions
      during the course of their regression. To the best of our knowledge, this is the
      first report in the English literature with sonographic depiction of spontaneous
      thrombosis of a hepatic posttraumatic pseudoaneurysm in a child.

PMID- 12523616
TI  - Sonography of macrocysts in infantile polycystic kidney disease.
AB  - The typical sonographic appearance of autosomal recessive polycystic kidney
      disease (ARPKD) has been described as symmetrically enlarged, echogenic kidneys
      with occasional visualization of small cysts. Modern sonographic equipment,
      however, allows a greater ability to show parenchymal detail, and multiple tiny
      cysts and occasionally dilated tubular structures have become apparent. In this
      report, we describe sonographic findings of ARPKD that are quite similar to the
      macroscopic appearance. Sonographic images show unusual focal rosettes consisting
      of a cluster of the radially oriented, dilated collecting tubules that are
      apparent on pathologic evaluation. It is important to recognize the focal rosette
      as a manifestation of ARPKD.

PMID- 12523617
TI  - AIUM standard for the performance of breast ultrasound examination.

PMID- 12523618
TI  - AIUM standard for the performance of ultrasound examination of the extracranial
      cerebrovascular system.

PMID- 12523619
TI  - AIUM standard for the performance of saline infusion sonohysterography.

PMID- 12523620
TI  - Mutations in gyrA and parC QRDRs are not relevant for quinolone resistance in
      epidemiological unrelated Stenotrophomonas maltophilia clinical isolates.
AB  - Clinical strains of Stenotrophomonas maltophilia are often highly resistant to
      multiple antibiotics and this resistance is steadily rising. Quinolones are
      included in the group of antimicrobial agents to which this microorganism is
      developing resistance. Therefore, the aim of this study was to analyze the
      epidemiological relationship among 22 clinical isolates of S. maltophilia as well
      as the molecular mechanisms responsible for the acquisition of quinolone
      resistance in these strains. The results of the pulsed-field gel electrophoresis
      (PFGE) showed an heterogenicity of 82% among the strains used in the study. On
      the other hand, no amino acid changes were found in the quinolone resistance
      determining region (QRDR) of either gyrA and parC genes among quinolone
      susceptible and -resistant S. maltophilia strains. Besides, the amino acid of the
      GyrA found in the position equivalent to Ser-83 of E. coli was Gln instead of a
      Ser or Thr, the amino acids usually encountered in this position among Gram
      negative bacteria. The results suggest that there is not a relationship between
      the presence of this Gln and the resistance to quinolones in S. maltophilia. We
      can conclude that, contrary to what has been described in other microorganisms,
      in these S. maltophilia isolates, the development of resistance to quinolones was
      not related to mutations in the QRDR of gyrA and parC genes. Thus, to our
      knowledge, this is the first report describing this phenomenon.

PMID- 12523621
TI  - Physiology and antibiotic susceptibility of Staphylococcus aureus small colony
      variants.
AB  - Small colony variants (SCV) are slow-growing subpopulations with altered
      metabolism and reduced antibiotic susceptibility which, in the case of
      Staphylococcus aureus, can cause persisting and recurrent infections. We studied
      four SCVs and their corresponding parent strains: one clinical strain pair, one
      menaquinone-deficient spontaneous mutant, and two constructed mutants obtained by
      inactivation of hemB in S. aureus 8325-4 and COL, respectively. SCVs growing in
      chemically defined medium (CDM) with glucose limitation and enhanced buffering
      capacity were found to generate deltapsi of -120 to -140 mV, which is comparable
      to the parent strains. However, glucose is consumed inefficiently with small
      growth yields. In contrast to wild-type strains, deltapsi dropped immediately to
      values below -100 mV when glucose expired and other nutrients such as acetate and
      lactate did not allow for further growth. Accordingly, the sensitivity of SCVs
      toward antibiotics known to be taken up through deltapsi, such as
      aminoglycosides, dropped 10- to 30-fold when compared to the parent strain under
      routine MIC determination conditions. When growing in CDM, the susceptibility of
      SCVs varied according to the magnitude of deltapsi.

PMID- 12523622
TI  - Characterization of an integron carrying a new class D beta-lactamase (OXA-37) in
      Acinetobacter baumannii.
AB  - Integrons from a clinical strain of Acinetobacter baumannii highly resistant to
      beta-lactams have been analyzed. The largest (2.2 kb) contained three gene
      cassettes: an aacA4, an open reading frame of 417 nucleotides, and an OXA-type
      encoding gene. The oxa gene nucleotide sequence differed from that of the oxa-20
      in 2 bp, one of the mutations being silent. The nonsilent mutationgenerated a
      substitution of glutamic acid for aspartic acid. The new OXA has been named OXA
      37.

PMID- 12523623
TI  - Molecular characterization of amoxicillin-clavulanate resistance in a clinical
      isolate of Escherichia coli.
AB  - The resistance phenotype of the clinical isolate of Escherichia coli 1941 was
      characterized by high-level resistance to penicillins and to combinations
      amoxicillin-ticarcillin/clavulanate and ampicillin/sulbactam. This resistance was
      carried by the conjugative plasmid pEC1941 that encoded a beta-lactamase
      activity. The purified enzyme focused at pI 5.4 and was strongly inhibited in
      vitro by clavulanic acid (IC50 = 0.09 microM). Nucleotide sequence analysis
      revealed identity between the plasmid borne blaTEM gene of E. coli 1941 and the
      blaTEM-1B gene, except for a single C-to-T substitution at position 32 in the
      promoter region leading to the overlapping promoters Pa and Pb. No alterations in
      the expression of outer membrane porins OmpC and OmpF have been detected. These
      findings show that the resistance of E. coli 1941 to the combinations of beta
      lactams with beta-lactamase inhibitors is related to high-level production of TEM
      1 enzyme expressed from the strong promoters Pa and Pb.

PMID- 12523624
TI  - Multiple drug-resistant Mycobacterium tuberculosis: evidence for changing fitness
      following passage through human hosts.
AB  - Recent studies have shown a difference in the genotype of resistant bacteria
      following passage in animals compared to those passaged in vitro. This suggests
      that organisms rapidly adapt to their environment of growth. We sought to
      investigate whether this phenomenon occurred in human infection and whether
      changes could be detected in the fitness (growth velocity) of isolates
      transmitted between human hosts. Isogenic strains of Mycobacterium tuberculosis
      were obtained from a well-documented hospital outbreak. The subjects included
      those who were HIV seropositive and immunocompromised. The relative fitness of
      each sample was measured using growth competition in vitro. The results confirmed
      that our method of measuring fitness was not influenced by the storage conditions
      of the isolates, and demonstrated that the fitness of genetically similar
      isolates obtained from different patients in the outbreak differed significantly,
      as reflected in the growth velocity of the strains. This study provides the first
      evidence that multiple drug resistant M. tuberculosis strains adapt to the
      environment of their human host.

PMID- 12523625
TI  - The AcrB multidrug transporter plays a major role in high-level fluoroquinolone
      resistance in Salmonella enterica serovar typhimurium phage type DT204.
AB  - Salmonella enterica serovar Typhimurium phage type DT204 strains isolated from
      cattle and animal feed in Belgium were characterized for high-level
      fluoroquinolone resistance mechanisms [MICs to enrofloxacin (Enr) and
      ciprofloxacin (Cip), 64 and 32 microg/ml, respectively]. These strains isolated
      during the periods 1991-1994, and in 2000 were clonally related as shown by
      pulsed-field gel electrophoresis (PFGE). Selected strains studied carried several
      mutations in the quinolone target genes, i.e., a double mutation in the quinolone
      resistance-determining region (QRDR) of gyrA leading to amino acid changes
      Ser83Ala and Asp87Asn, a single mutation in the QRDR of gyrB leading to amino
      acid change Ser464Phe, and a single mutation in the QRDR of parC leading to amino
      acid change Ser80Ile. Moreover, Western blot analysis showed overproduction of
      the AcrA periplasmic protein belonging to the AcrAB-ToIC efflux system. This
      suggested active efflux as additional resistance mechanism resulting in a
      multiple antibiotic resistance (MAR) phenotype, which was measurable by an
      increased level of resistance to the structurally unrelated antibiotic
      florfenicol in the absence of the specific floR resistance gene. The importance
      of the AcrAB-TolC efflux system in high-level fluoroquinolone resistance was
      further confirmed by inactivating the acrB gene coding for the multidrug
      transporter. This resulted in a 32-fold reduction of resistance level to Enr (MIC
      = 2 microg/ml) and actually in a susceptible phenotype according to clinical
      breakpoints. Thus, AcrB plays a major role in high-level fluoroquinolone
      resistance, even when multiple target gene mutations are present. The same effect
      was obtained using the recently identified efflux pump inhibitor (EPI) Phe-Arg
      naphthylamide also termed MC207,110. Among several fluoroquinolones tested in
      combination with EPI, the MIC of Enr was reduced most significantly. Thus, using
      EPI together with fluoroquinolones such as Enr may be promising in combination
      therapy against high-level fluoroquinolone-resistant S. enterica serovar
      Typhimurium.

PMID- 12523626
TI  - Cellular location and function of the P-glycoproteins (EhPgps) in Entamoeba
      histolytica multidrug-resistant trophozoites.
AB  - We have studied the cellular location and the efflux pump function of the
      Entamoeba histolytica P-glycoproteins (EhPgps) in drug-sensitive and -resistant
      trophozoites. Polyclonal antibodies against the EhPgp384 polypeptide (375-759
      amino acids) revealed a 147-kDa protein by Western blot. The band intensity
      correlated with the emetine-resistance of the trophozoites. Through the confocal
      microscope, using the anti-EhPgp384 and fluorescein secondary antibodies, the
      EhPgps were found in a complex vesicular network, in the plasma membrane and
      outside of the cells. Transmission electron microscopy assays confirmed that drug
      resistant trophozoites presented four to five times more EhPgps than sensitive
      cells. Fluorescence co-localization experiments using rhodamine-123 (R123) and
      the anti-EhPgp384 antibodies suggested the interaction between EhPgps and the
      drug. R123 efflux kinetics evidenced that the emetine-resistant trophozoites
      displayed a drug efflux kinetic four times higher than the drug-sensitive
      trophozoites, which was reduced by verapamil in both cases. EhPgps may
      participate in avoiding drug accumulation in the trophozoites by two putative
      mechanisms: (1) the direct extrusion of the drug from the plasma membrane, and
      (2) an indirect transport mechanism in which the drug is trapped by EhPgps and
      concentrated within vesicles that drive the drug to the plasma membrane.

PMID- 12523627
TI  - Clonal and antibiotic resistance profiles of methicillin-resistant Staphylococcus
      aureus (MRSA) from a Portuguese hospital over time.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from a
      general hospital in Oporto, Portugal, during two periods (1992-1993 and 1996
      2000) were characterized by pulsed-field gel electrophoresis (PFGE) of SmaI
      fragments, and by hybridization of ClaI digests with mecA and Tn554 probes,
      discriminating the isolates in mecA::Tn554::PFGE genotypes. In addition, a
      representative sample of the defined genotypes was characterized by multilocus
      sequence typing (MLST) and SCCmec (staphylococcal cassette chromosome mec)
      typing, generating the corresponding ST-SCCmec types. In 1992-1993, 77% of MRSA
      belonged to the Iberian clone (genotype I::E::A or ST247-IA). In 1996-2000, the
      frequency of this clone decreased to 19% and the majority (69%) of the isolates
      belonged to another international clone, the Brazilian MRSA (genotype XI::B::B or
      ST239-IIIA). Trimethoprim/sulfamethoxazole (SXT) was confirmed to be an important
      phenotypic marker to distinguish the Iberian (SXT-susceptible) and the Brazilian
      (SXT-resistant) clones in MRSA isolates from Portugal. Our observations document
      major shifts in the dominant MRSA clonal types that occurred in this hospital
      since 1992, suggesting a selective advantage of the Brazilian relatively to the
      Iberian clone. In addition to these two MRSA clones that are the most frequent in
      Portuguese hospitals since the early 1990s, sporadic MRSA clones (representing
      14% of the total) were identified and characterized.

PMID- 12523628
TI  - Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to
      2000: increased susceptibility of Candida species to fluconazole.
AB  - The incidence of nosocomial Candida fungemia increased 36-fold from 1981
      (0.8/10,000 discharges) to 2000 (28.8/10,000 discharges) at the National Taiwan
      University Hospital, a 2000-bed teaching hospital in northern Taiwan. To
      understand the current status of resistance to available antifungal agents among
      Candida species causing invasive infections, the in vitro susceptibilities of 222
      isolates (collected from July, 1999-June, 2001) were determined. Among all of the
      Candida species tested, 6% and 7% were resistant to fluconazole and itraconazole,
      respectively. The MIC90 values of voriconazole and amphotericin B were 0.5 and 1
      microg/ml, respectively, although some isolates of C. krusei (amphotericin B and
      voriconazole MIC, >64 microg/ml) and C. tropicalis and C. glabrata (voriconazole
      MICs, >64 microg/ml) were less susceptible to voriconazole or amphotericin B.
      About one-half of the C. glabrata isolates belonged to susceptible dose-dependent
      (SDD, 36%) or resistant (12%) categories for fluconazole and 96% belonged to SDD
      (56%) or resistant (40%) category for itraconazole. When compared with
      fluconazole susceptibility data of blood Candida isolates recovered from patients
      treated at the same hospital (NTUH) from two different time periods (January,
      1994, to June, 1995, and January, 1997, to June, 1999 described in previous
      reports), the incidence of increased susceptibility of non-krusei Candida
      isolates to fluconazole was evident. This trend of increasing susceptibility for
      fluconazole did not correlate to the increasing use of this agent in the
      hospital. None of the random amplified polymorphic DNA patterns generated by
      arbitrarily primed PCR using four random oligonucleotide primers for 14 isolates,
      which exhibited fluconazole MICs of > or = 16 microg/ml, were identical,
      indicating an absence of clonal dissemination among these isolates in the
      hospital.

PMID- 12523629
TI  - Mechanisms of antibiotic resistance in Escherichia coli isolates obtained from
      healthy children in Spain.
AB  - Antibiotic resistance and mechanisms involved were studied in Escherichia coli
      isolates from fecal samples of healthy children. Fifty fecal samples were
      analyzed, and one colony per sample was recovered and identified by biochemical
      and molecular tests. Forty-one E. coli isolates were obtained (82%). MIC testing
      was performed by agar dilution with 18 antibiotics, and the mechanisms of
      resistance were analyzed. Ampicillin resistance was detected in 24 isolates
      (58.5%), and blaTEM, blaSHV, and blaOXA type genes were studied by PCR and
      sequencing. The following beta-lactamases were detected (number of isolates): TEM
      (20), SHV-1 (1), and OXA-30 (1). The number of aminoglycoside-resistant isolates
      detected was as follows: streptomycin (15), tobramycin (1), gentamicin (1), and
      kanamycin (4). The aac(3)-IV gene was detected in the only gentamicin-resistant
      isolate. Nine (22%) and 2 (5%) isolates showed nalidixic acid (NALR) and
      ciprofloxacin resistance (CIPR), respectively. Mutations in GyrA and ParC
      proteins were shown in both NAL(R)-CIP(R) isolates and were the following: (1)
      GyrA (S83L + D87N), ParC (S801); and (2) GyrA (S83L + A84P), ParC (S80I + A108V).
      A single mutation in the S83 codon of the gyrA gene was found in the remaining
      seven NAL(R)-CIP(S) isolates. Tetracycline resistance was identified in 21
      isolates (51%) and the following resistance genes were found (number of
      isolates): tetA (12), tetB (5), and tetD (1). Chloramphenicol resistance was
      detected in five isolates (12%). These results show that the intestinal tract of
      healthy children constitutes a reservoir of resistant bacteria and resistance
      genes.

PMID- 12523630
TI  - A clinical strain of Escherichia coli possessing CMY-2 plasmid-mediated amp C
      beta-lactamase: an emerging concern in pediatrics?
AB  - A 5-year-old child was colonized by an isolate of Escherichia coli that
      transferred resistance to third-generation cephalosporins and cefoxitin. This
      resistance phenotype was encoded on a >75-kb plasmid pLRM 22. The transferable
      plasmid contained both blaCMY-2 and blaTEM-1b. Increasing reports of CMY-2 beta
      lactamase in clinical isolates in children raise concerns about the empiric use
      of third-generation cephalosporins in this patient group.

PMID- 12523631
TI  - Selection and characterization of fluoroquinolone-resistant mutants of
      Campylobacter jejuni using enrofloxacin.
AB  - Significant levels of fluoroquinolone resistance were obtained in
      Campylobacterjejuni isolates after an unique step of selection using
      enrofloxacin. An Asp90-to-Asn and a Thr86-to-Ile change in the gyrase subunit
      GyrA were found associated with a low (MIC < or = 8 /microg/ml) or a high (MIC >
      or = 16 microg/ml) level of resistance to ciprofloxacin, respectively. An
      association of both mutations conferred a higher level of resistance (MIC > or =
      128 microg/ml). Further steps of selection increased the MICs of fluoroquinolones
      but did not result in a multiple antibiotic resistance phenotype. The Thr86-to
      Ile change was found to confer different levels of resistance, pointing out other
      mechanisms of resistance. However, sequencing revealed no mutation in gyrB, and
      several attempts did not enable any amplification of the parC gene coding for
      topoisomerase IV, suggesting an absence of this secondary target in C. jejuni. In
      addition, no difference in the major outer membrane protein expression was found
      among the isolates. Furthermore, the use of the recently identified efflux pump
      inhibitor Phe-Arg-beta-naphthylamide did not result in a significant decrease of
      fluoroquinolone MICs or change in the frequency of isolation of enrofloxacin
      resistant mutants, and thus appears ineffective against fluoroquinolone-resistant
      C. jejuni isolates. Results obtained during ciprofloxacin accumulation studies
      confirmed that efflux probably plays a minor role in fluoroquinolone resistance
      of C. jejuni.

PMID- 12523632
TI  - WHO global salm-surv external quality assurance system (EQAS): an important step
      toward improving the quality of Salmonella serotyping and antimicrobial
      susceptibility testing worldwide.
AB  - Initiated in 2000, WHO Global Salm-Surv is a global network of epidemiologists
      and microbiologists involved in Salmonella surveillance. WHO Global Salm-Surv
      seeks to enhance the capacity of national and regional reference laboratories to
      conduct Salmonella serotyping and antimicrobial susceptibility testing through
      international training courses and an External Quality Assurance System (EQAS).
      In 2000, 44 WHO Global Salm-Surv member laboratories from 35 countries determined
      the serotype and antimicrobial susceptibility pattern for eight "blinded"
      Salmonella isolates. For serotyping, 73% of the results were correct. For
      susceptibility testing, 92% of the results were in agreement with the expected
      results. However, only 78% of the performed tests with the E. coli ATCC 25922
      reference strain were within the quality control range specified by National
      Committee for Clinical Laboratory Standards (NCCLS) guidelines. These EQAS
      results demonstrate the need for further training to improve the performance of
      some of the laboratories. WHO Global Salm-Surv activities, including
      international training courses and EQAS, represent an important step toward
      improving the quality of Salmonella serotyping and antimicrobial susceptibility
      testing worldwide, and improving the current reliability and comparability of
      Salmonella surveillance data obtained from different countries,

PMID- 12523633
TI  - Persistence of vancomycin-resistant enterococci (VRE) in broiler houses after the
      avoparcin ban.
AB  - The glycopeptide growth promoter avoparcin was banned from animal production in
      the EU in 1997 due to concern for the spread of vancomycin-resistant enterococci
      (VRE) from food animals to humans. In recent Norwegian and Danish studies,
      extensive occurrence of VRE on broiler farms and in broiler flocks after the
      avoparcin ban has been reported. The present study was undertaken to investigate
      the epidemiology of VRE on broiler farms in the absence of the selective pressure
      exerted by avoparcin. Environmental samples were obtained from five broiler
      houses after depopulation, cleaning, and disinfection of the houses between
      rotations, and two consecutive broiler flocks from each house were sampled by
      taking cloacal swabs from the broilers at the time of slaughter. A total of 69
      vancomycin-resistant Enterococcus faecium isolates obtained from broiler flocks
      and broiler houses were subjected to molecular typing by pulsed-field gel
      electrophoresis (PFGE). Forty-one PFGE-profiles were observed. VRE with
      indistinguishable or highly similar PFGE profiles were isolated from consecutive
      broiler flocks and from environmental samples from the houses in which the flocks
      were reared, whereas VRE-isolates from different broiler houses and from flocks
      reared in different houses appeared to be genetically unrelated. These findings
      indicated that VRE was transmitted between consecutive broiler flocks by clones
      of resistant bacteria surviving in the broiler houses despite cleaning and
      disinfection between rotations. Thus, the extensive occurrence of VRE in broiler
      flocks after the avoparcin ban may be explained by persistence of VRE in the
      broiler house environment.

PMID- 12523634
TI  - Genetic linkage between erm(B) and vanA in Enterococcus hirae of poultry origin.
AB  - Vancomycin-resistant enterococci (VRE) have frequently been isolated from
      Norwegian poultry production following the prohibition of the glycopeptide growth
      promoter avoparcin since 1995. In the present study, a close genetic linkage
      between the vanA and erm(B) determinants in an Enterococcus hirae isolate of
      poultry origin is demonstrated, a result that indicates a mechanism for co
      selection and maintenance of vancomycin resistance in absence of selective
      pressure from avoparcin. A total of 36 vanA-positive enterococci of poultry
      origin, also phenotypically resistant to erythromycin and/or tetracycline, were
      analyzed by PCR for identification of erm and tet resistance determinants. An E.
      hirae isolate harbored erm(B) and tet(K), and in this isolate vanA and erm(B)
      were located on a BamHI fragment of an approximately 50-kb plasmid. Approximately
      3 kb of this fragment was amplified by PCR with vanA and erm(B) primers. Sequence
      analysis of the region between erm(B) and vanZ of Tn1546 showed a truncated
      IS1216V inserted downstream of the erm(B) stop codon, aligned with a conserved
      copy of the 3'-inverted terminal repeat of Tn1546. Mating experiments with the E.
      hirae isolate as donor and E. faecalis JH2-2 as recipient did not result in any
      transconjugants, indicating that the vanA/erm(B)-carrying plasmid was
      nonconjugative under the given experimental conditions.

PMID- 12523635
TI  - Streptogramin resistance among Enterococcus faecium isolated from production
      animals in Denmark in 1997.
AB  - The genetic background for streptogramin resistance was examined in Enterococcus
      faecium isolated from pigs (n = 55) and broilers (n = 207) in 1997 in Denmark.
      Fifty-one percent and 67%, respectively, of the isolates were resistant to
      streptogramins. Among streptogramin-resistant E. faecium (SREF), the genetic
      background for streptogramin A resistance could be determined in 96% of the
      isolates from broilers, compared with 14% among SREF from pigs. For broiler
      isolates 89% of SREF contained the vat(E) gene and 10% the vat(D) gene. Three of
      these isolates contained both resistance genes. Among SREF from pigs two isolates
      contained the vat(E) gene and two others the vat(D) gene. The genetic background
      for streptogramin B was most often identified as the erm(B) gene encoding
      macrolide, lincosamide, and streptogramin B (MLSB) resistance. Among SREF, 84%
      and 86% of isolates from broilers and pigs, respectively, contained the erm(B).
      In SREF from broilers, the erm(B) gene was physically linked to the vat(E) gene
      in 62% of the vat(E)-positive isolates and 79% of the isolates containing vat(D).
      erm(A) was detected in two SREF of broiler origin. Both isolates also contained
      the erm(B) gene. No SREF contained the vgb(A) gene encoding streptogramin B
      resistance. On the basis of genetic characterization, streptogramin-resistant
      isolates from broiler were divided into subgroups, according to the presence of
      the streptogramin A genes, to determine possible co-resistance to antimicrobials,
      especially glycopeptides. Twenty-five percent of the SREF from broilers were
      glycopeptide resistant (MIC > 16 microg/ml). None of the isolates containing the
      streptogramin A gene vat(D) was resistant to glycopeptide, whereas isolates
      containing the vat(E) gene had a lower prevalence to glycopeptide resistance than
      the streptogramin-sensitive isolates.

PMID- 12523636
TI  - Phenotypic and genotypic characterization of food animal isolates of Salmonella
      with reduced sensitivity to ciprofloxacin.
AB  - Reports of nontyphoidal Salmonella enterica subsp. enterica showing reduced
      sensitivity to ciprofloxacin (RSC) have increased rapidly during the past decade.
      Infection in humans with Salmonella possessing RSC may compromise the
      effectiveness of ciprofloxacin therapy. Nineteen among 4,357 Salmonella strains
      isolated from food animals in Canada from 1998 to 1999 showed RSC; 17 were from
      turkeys and 2 from chickens. All were resistant to nalidixic acid and
      sulfisoxazole and possessed RSC at a level of 0.125-0.5 microg/ml. PCR-RFLP of
      the gyrA quinolone resistance-determining region (QRDR) with Hinfl revealed that
      S. Bredeney and S. Heidelberg isolates possessed a mutation in this region.
      Single-strand conformational polymorphism (SSCP) analysis showed that S.
      Schwarzengrund and S. Senftenberg isolates also possessed a point mutation in the
      QRDR. DNA sequencing confirmed the findings and showed that all isolates
      possessed a base substitution in the gyrA QRDR. Sequencing revealed no mutations
      in the gyrB and silent wobble mutations in the parC QRDR. Reserpine, a known
      efflux pump inhibitor, did not effect the MICs for ciprofloxacin, nalidixic acid,
      and tetracycline. The mar operon could be induced in all isolates at 37 degrees C
      and in 18 of 19 at 30 degrees C; induction resulted in a two- to four-fold
      increase in the MIC of ciprofloxacin. In 14 of the 19 isolates, the mutation rate
      was two-fold or higher than in a ciprofloxacin sensitive S. Bredeney and S.
      Typhimurium LT2 control strain. Examination of clonal relatedness using pulsed
      field gel electrophoresis (PFGE) and plasmid profiles indicated that some degree
      of clonal dispersion may have occurred, but the majority of isolates may have
      arisen from de novo mutations.

PMID- 12523637
TI  - Within-sample and between-sample variation of antimicrobial resistance in fecal
      Escherichia coli isolates from pigs.
AB  - The present study was initiated to evaluate the effect of sampling time and
      within-sample variability on the diversity in antimicrobial resistance patterns
      in fecal Escherichia coli from healthy pigs. Isolates were tested against 11
      antimicrobials. A total of 25 different profiles were observed, involving
      resistance to ampicillin, streptomycin, tetracycline, sulfonamides, trimethoprim,
      and/or a trimethoprim/sulfonamide combination. No isolates were resistant to
      enrofloxacin, gentamicin, or chloramfenicol, whereas resistance against neomycin
      and nalidixic acid was sporadically detected in isolates from grower pigs. A
      model that clusters pigs within-sampling time as a repeated factor and clusters
      isolates within individual pigs as a random factor was used. For sows, the
      variance component ratio of sampling time to residuals was 0.28-0.56 for the
      different antimicrobials (except ampicillin) and 0.85-1.79 for grower pigs. The
      variance components for within-sample variation were zero or close to zero,
      except in isolates from sows where resistance to ampicillin explained 14.8 times
      more of the variation compared to residuals. Thus, the effect of an animal's
      status at a given sampling time was more influential on the variability in
      antimicrobial resistance than within-animal diversity. We conclude that repeated
      sampling and analysis of one isolate per animal each time may be preferable for
      screening general tendencies, whereas several isolates have to be tested when
      individual animals are focused.

PMID- 12523638
TI  - Resistance to quaternary ammonium compounds in food-related bacteria.
AB  - Microbial resistance to antimicrobial agents continues to be a major problem. The
      frequent use and misuse of disinfectants based on quaternary ammonium compounds
      (QACs) in food-processing industries have imposed a selective pressure and may
      contribute to the emergence of disinfectant-resistant microorganisms. A total
      number of 1,325 Gram-negative isolates (Escherichia coli, other coliforms Vibrio
      spp., and Aeromonas spp.) and 500 Enterococcus spp. from food and food-processing
      industries and fish farming were screened for natural resistance to the QAC-based
      disinfectant benzalkonium chloride (BC). Of the 1,825 isolates, 16 strains,
      mainly from meat retail shops, showed low-level resistance to BC. None of the
      Enterococcus spp. from broiler, cattle, and pigs, the antibiotic-resistant E.
      coli from pig intestine and fish pathogens Vibrio spp. and Aeromonas spp. from
      the Norwegian fish farming industry were resistant to BC. The BC-resistant
      strains were examined for susceptibility to 15 different antibiotics,
      disinfectants, and dyes. No systematic cross-resistance between BC and any of the
      other antimicrobial agents tested was detected. Stable enhanced resistance in
      Enterobacter cloacae isolates was demonstrated by step-wise adaptation in
      increasing concentrations of BC. In conclusion, BC resistance among food
      associated Gram-negative bacteria and Enterococcus spp. is not frequent, but
      resistance may develop to user concentrations after exposure to sublethal
      concentrations of BC.

PMID- 12523639
TI  - Dissemination of vancomycin-resistant enterococci harboring vanA through disposal
      of waste derived from industrial production of vancomycin.
AB  - We demonstrated the occurrence of vancomycin-resistant enterococci (VRE) in waste
      derived from the industrial production of vancomycin and their dissemination
      through disposal of such waste into a sewage treatment plant. Bacteriological
      counts on a medium selective for enterococci (Slanetz-Bartley agar) revealed the
      presence of high numbers of presumptive VRE (approximately 10(6) CFU/ml) in the
      waste originating from the fermentation biomass used for vancomycin production.
      The waste was also found to contain active residues of vancomycin (64-1,024
      microg/ml) by bioassays using a vancomycin-susceptible enterococcal strain.
      Randomly amplified polymorphic DNA (RAPD) analysis of 65 presumptive VRE isolates
      from the waste allowed distinction of four genotypes, two of which (A and D)
      belonged to the genus Enterococcus, most likely E. faecium, and harbored the vanA
      gene conferring high-level vancomycin resistance. The same VRE strains found in
      the waste occurred also in the biological tanks and the final effluent of the
      sewage treatment plant receiving the waste, as demonstrated by the detection of
      undistinguishable pulsed-field gel electrophoresis (PFGE) patterns in VRE
      isolated from these sources. These results indicate the need to assess the
      possible dissemination of VRE and other antibiotic-resistant bacteria through
      disposal of waste derived from antibiotic production.

PMID- 12523640
TI  - Antimicrobial resistance of Salmonella serotypes isolated from slaughter-age pigs
      and environmental samples.
AB  - The aim of this study was to determine the antimicrobial resistance patterns of
      Salmonella strains isolated from slaughter-age pigs and environmental samples
      collected at modern swine raising facilities in Brazil. Seventeen isolates of six
      serotypes of Salmonella enterica subsp. enterica were isolated out of 1,026
      collected samples: Salmonella Typhimurium (1), Salmonella Agona (5), Salmonella
      Sandiego (5), Salmonella Rissen (1), Salmonella Senftenberg (4), and Salmonella
      Javiana (1). Resistance patterns were determined to extended-spectrum penicillin
      (ampicillin), broad-spectrum cephalosporins (cefotaxime and ceftriaxone),
      aminoglycosides (streptomycin, neomycin, gentamicin, amikacin, and tobramycin),
      narrow-spectrum quinolone (nalidixic acid), broad-spectrum quinolone
      (ciprofloxacin and norfloxacin), tetracycline, trimethoprim, and chloramphenicol.
      Antimicrobial resistance patterns varied among serotypes, but isolates from a
      single serotype consistently showed the same resistance profile. All isolates
      were resistant to tetracycline, streptomycin, and nalidixic acid. One isolate,
      Salmonella Rissen, was also resistant to cefotaxime and tobramycin. All serotypes
      were susceptible to ceftriaxone, norfloxacin, ciprofloxacin, ampicillin,
      gentamicin, and chloramphenicol. The high resistance to tetracycline and
      streptomycin may be linked to their common use as therapeutic drugs on the tested
      farms. No relation was seen between nalidixic acid and fluoroquinolone
      resistance.

PMID- 12523641
TI  - Engineering new peptidic inhibitors from a natural chymotrypsin inhibitor.
AB  - Three model peptides of different sizes (17-24 amino acid residues) mimicking the
      chymotrypsin inhibitor SCGI (a peptide of 35 amino acid residues) isolated from
      Schistocerca gregaria were designed and prepared by convergent peptide synthesis.
      Selective formation of disulphide bridges in the closing step was achieved
      without selective protection of cysteine residues. The natural pattern of the two
      disulphide bridges was determined by 2D homonuclear 1H NMR techniques. All three
      model peptides were characterized by amino acid analysis. MS and CD spectra.
      Preliminary results revealed that the two smaller model peptides exhibit no
      Inhibitory activity, whereas the larger one shows limited inhibition of
      chymotrypsin.

PMID- 12523642
TI  - A new peptidic protease inhibitor from Vicia faba seeds exhibits antifungal, HIV
      1 reverse transcriptase inhibiting and mitogenic activities.
AB  - A new trypsin-chymotrypsin Inhibitor, with an N-terminal sequence showing some
      differences from the previously reported trypsin-chymotrypsin inhibitor, was
      isolated from the broad bean Vicia faba. The inhibitor was a peptide with a
      molecular mass of 13 kDa. It was adsorbed on Affi-gel blue gel and CM-Sepharose.
      It exerted antifungal activity toward Mycosphaerella arachidicola and
      Physalospora piricola. In addition, the trypsin-chymotrypsin inhibitor elicited a
      mitogenic response from mouse splenocytes and inhibited the activity of human
      immunodeficiency virus-1 reverse transcriptase.

PMID- 12523643
TI  - Synthesis of N(alpha)-Boc-N(epsilon)-tetrabenzyl-DTPA-L-lysine and N(alpha)-Fmoc
      N(epsilon)-tetra-t-butyl-DTPA-L-lysine, building blocks for solid phase synthesis
      of DTPA-containing peptides.
AB  - Two building blocks, Boc-Lys(Bn4-DTPA)-OH and Fmoc-Lys(Bu4(t)-DTPA)-OH have been
      synthesized via the acylation of the epsilon-amino group of N(alpha)-protected
      lysine, using suitably protected tetra-esters of diethylene triamine pentaacetic
      acid (DTPA), a ligand with wide application as a chelating agent for complexing
      metal tons to peptides.

PMID- 12523644
TI  - Electron paramagnetic resonance backbone dynamics studies on spin-labelled
      neuropeptide Y analogues.
AB  - Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous
      system of mammalians. NPY acts by binding to at least five G-protein coupled
      receptors (GPCRs) which have been named Y1, Y2, Y4, Y5 and Y6. Three spin
      labelled NPY analogues containing the nitroxide group of the amino acid TOAC
      (2.2.6.6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) as a
      paramagnetic probe were synthesized by solid-phase peptide synthesis. Synthetic
      problems owing to the sensitivity of nitroxide towards acidic and reducing
      conditions have been overcome by using a cleavage cocktail that contains anisole
      and cresol scavengers. Concerning the receptor binding preferences, the analogues
      [TOAC34]-pNPY and [Ala31, TOAC32]-pNPY showed a marked selectivity for the Y5
      receptor, while [TOAC2]-pNPY maintained a significant binding also to the Y2
      receptor subtype. The modifications of the native peptide structure caused by the
      introduction of TOAC were examined by circular dichroism. In order to determine
      the rotational correlation time of the spin probes, electron paramagnetic
      resonance measurements were performed in solution and in the presence of
      liposomes. This allowed us to evaluate the backbone dynamics of the different
      parts of the NPY molecule in the free and membrane bound states. The results of
      these studies showed that NPY Interacts with liposomes by using the C-terminal
      alpha-helix while the N-terminal tail retains a flexibility that is comparable to
      that of the peptide in solution as already shown by NMR studies on DPC micelles.
      Furthermore, we demonstrated that TOAC-labelllng is a valuable tool to
      investigate changes in the backbone conformation and dynamics. This may be of
      major importance for peptides and small proteins when they bind to cell
      membranes.

PMID- 12523645
TI  - Rabbit anti-HMG-17 antibodies recognize similar epitopes on the HMG-17 molecule
      as lupus autoantibodies. Relation with histone H1 defined epitopes.
AB  - HMG-17 is a nucleosomal protein which is an immune target of autoantibodies in
      systemic lupus erythematosus (SLE) and other autoimmune diseases. Autoantibody
      production in SLE is believed to result from autoantigen specific immune
      stimulation and subsequently, it is expected that antigenic determinants
      recognized by SLE autoantibodies and induced antibodies by immunization are quite
      similar. To examine this issue, rabbits were immunized with purified HMG-17. The
      produced antiserum showed cross reactivity on blots and in inhibition ELISA with
      histone H1, even after its affinity purification with immobilized HMG-17.
      Finally, purification of the antiserum over H1 absorbed on nitrocellulose
      membrane produced specific anti-HMG-17 antibodies in the supernatant and anti-HMG
      17/H1 antibodies that were bound to H1. SLE sera positive for HMG-17 had also
      cross reactivity with H1, and following the same procedure as before we received
      HMG-17 specific SLE autoantibodies and anti-HMG-17/H1 autoantibodies. Using the
      multipin epitope mapping technology, 19 overlapping 15-mer HMG-17 peptides and
      six 15-peptides, corresponding to known epitopes of histone H1, were synthesized.
      Four major epitopes were identified on the HMG-17 molecule, reactive with induced
      anti-HMG-17 antibodies, and these were the same as major autoepitopes In SLE. The
      sequence 25-51 of HMG-17, part of its DNA-binding domain, was recognized by the
      anti-HMG-17/H1 antibodies that were bound to H1. These antibodies recognized also
      defined epitopes of H1. Our results show that SLE autoantibodies can be directed
      against the same or similar epitopes as do IgGs evoked during the active
      immunization of animals, and provide additional evidence that autosensitization
      with an autoantigen might be operative. The possibility that the same or similar
      epitopes are found on different molecules (in this study HMG-17 and H1) supports
      the fact that there are rules by which nature selects the most dominant
      immunodeterminant to a given protein, which often represents functional or
      structural sites in the autoantigen.

PMID- 12523646
TI  - Structure and nucleotide sequence of Euphorbia characias copper/TPQ-containing
      amine oxidase gene.
AB  - A cDNA encoding for a copper containing amine oxidase has been isolated and
      sequenced from young leaves of Euphorbia characias, a perennial mediterranean
      shrub. A single long open reading frame of 2068 pb encodes a protein composed of
      653 amino acids with a molecular mass of about 74 kDa. A putative 24-aminoacid
      signal peptide precedes the sequence of the mature protein, with characteristics
      of a secretion signal peptide. Alignments of Euphorbia amine oxidase cDNA
      nucleotide sequence with that of amine oxidase from the seedlings of the pulses
      lentil, pea, and chickpea reveal several conserved regions, especially in the C
      terminus, with a homology 90%-97%. The near 5' region shows several insertions,
      deletions, and different nucleotide sequence with ca. 60% homology. The enzyme
      contains 1%-2% carbohydrate deduced by deglycosylation experiments. Five cysteine
      residues are present in the deduced aminoacid sequence with a single disulfide
      bridge as judged by titration with cysteine reagents.

PMID- 12523647
TI  - The effect of active site mutations in the oxaloacetate decarboxylase and
      pyruvate kinase-like activities of Anaerobiospirillum succiniciproducens
      phosphoenolpyruvate carboxykinase.
AB  - Anaerobiospirillum succiniciproducens His225Gln, Asp262Asn, Asp263Asn, and
      Thr249Asn phosphoenolpyruvate carboxykinases were analyzed for their oxaloacetate
      decarboxylase, and pyruvate kinase-like activities. The His225Gln and Asp263Asn
      enzymes showed increased Km values for Mn2+ and PEP compared with the native
      enzyme, suggesting a role of His225 and Asp263 in Mn2+ and PEP binding. No mayor
      alterations in Km values for oxaloacetate were detected for the varied enzymes.
      Alterations of His225, Asp262, Asp263, or Thr249, however, did not affect the
      Vmax of the secondary activities as much as they affected the Vmax for the main
      reaction. The results presented in this communication suggest different rate
      limiting steps for the primary reaction and the secondary activities.

PMID- 12523648
TI  - Arginine methylation of recombinant murine fibrillarin by protein arginine
      methyltransferase.
AB  - Fibrillarin is a conserved nucleolar SnoRNP with a diverse N-terminal glycine-
      and arginine-rich (GAR) domain in most eukaryotes. This region in human
      fibrillarin is known to contain modified dimethylarginines. In this report we
      demonstrate that recombinant murine fibrillarin is a substrate for protein
      arginine methyltransferase, including the purified recombinant enzyme (rat PRMT1
      and yeast RMT1) and the protein methyltransferases present in lymphoblastoid cell
      extracts. Our results of protease digestion, methylation competition reactions,
      and immunoblotting with a methylarginine-specific antibody all indicate that the
      methylation of fibrillarin is in the N-terminal GAR domain and arginyl residues
      are modified. Finally, amino acid analyses revealed that the modification of
      recombinant murine fibrillarin forms methylarginines, mostly as
      dimethylarginines.

PMID- 12523649
TI  - Primary structure and chemical modification of some amino acid residues of
      bifunctional alginate lyase from a marine bacterium Pseudoalteromonas sp. strain
      no. 272.
AB  - The entire amino acid sequence of bifunctional alginate lyase from
      Pseudoalteromonas sp. strain No. 272 were determined by two approaches, Edman
      degradation of the peptides obtained from protease digestion of the enzyme
      protein and analysis of PCR products of the structural gene. The former resulted
      in incomplete amino acid sequence in the entire sequence, due to lacking of the
      proper peptides from the protease digestion. To compensate for this lack of
      sequences we applied the method of PCR of the structural gene that was initially
      elucidated from the primers designed from N- and C-terminal amino acid sequences
      of the enzyme. The results of the amino acid sequences from these two approaches
      showed good agreement. The enzyme consisted of 233 amino acid residues with a
      molecular mass of 25,549.5, including the sole W and cystine residue. The
      sequence homology search among the other alginate lyases from different origins
      indicated that they were very weakly homologous, with the exception of the
      sequence homology (80.3%) of Pseudoalteromonas elyakovii alginate lyase. The
      consensus sequence, YFKhG + Y-Q (Wong, T. Y., Preston, L. A., and Schiller, N. L.
      2000. Annu. Rev. MicrobioL 54: 289-340) in the C-terminal regions was conserved.
      The kinetic analyses of chemical modification of some amino acid residues of the
      enzyme showed that W, K, and Y appeared to be important in the enzyme function.

PMID- 12523650
TI  - Preparation of biologically active recombinant human progastrin(1-80).
AB  - The bacterial expression of human progastrin(6-80) has been reported previously
      [Baldwin, G.S. et al. (2001) J. Biol. Chem. 276: 7791-7796]. The aims of the
      present study were to prepare full-length recombinant human progastrin(1-80) and
      to compare its biological activity with that of progastrin(6-80) in vitro, to
      determine whether or not the N-terminal five amino acids contributed to activity.
      A fusion protein of glutathione-S-transferase and human progastrin(1-80) was
      expressed in Escherichia coli, collected on glutathione-agarose beads, and
      cleaved with enterokinase. Progastrin(1-80) was purified by reversed-phase and
      anion exchange HPLC and characterized by radioimmunoassay, amino acid sequencing,
      and mass spectrometry. No differences were detected in the extent of stimulation
      by progastrin(1-80) and progastrin(6-80) in proliferation and migration assays
      with the mouse gastric cell line IMGE-5. We conclude that residues 1-5 of
      progastrin(1-80) are not essential for biological activity.

PMID- 12523651
TI  - Regioselective nitration of phenol induced by catalytic antibodies.
AB  - Catalytic antibodies with a metalloporphyrin cofactor represent a new generation
      of biocatalysts tailored for selective oxidations. Thus monoclonal antibodies,
      3A3, were raised against microperoxidase 8 (MP8), and the corresponding 3A3-MP8
      complexes were shown previously to have a high peroxidase activity. This paper
      shows that those complexes also catalyzed efficiently the nitration of phenol
      into 2- and 4-nitrophenol by NO2- in the presence of H2O2. pH dependence studies
      suggested that no amino acid from the antibody protein participated in the
      heterolytic cleavage of the O-O bond of H2O2. The inhibition of the reaction by
      cyanide and radical scavengers suggested a MP8-mediated peroxidase-like
      mechanism, involving the reduction of high-valent iron-oxo species by NO2- and
      phenol producing, respectively, NO2* and phenoxy radicals, which then reacted to
      give nitrophenols. Finally, the antibody protein appears to have two major roles:
      (i) it protects MP8 toward oxidative degradations and (ii) it induces a
      regioselectivity of the reaction toward the formation of 2-nitrophenol.

PMID- 12523652
TI  - Protein denaturant binding polynomials.
AB  - We show how moments of the denaturant binding distribution function can be
      extracted from experimental data on the denaturation of a protein as a function
      of the concentration of denaturant and how in turn these moments can be used to
      construct the denaturant binding distribution function. This approach is similar
      to our recent work on using the maximum-entropy method to construct ligand
      binding distributions from moments obtained from titration curves for nucleic
      acids and proteins. As an example we take literature data on the denaturation of
      ferro- and ferricytochrome c by guanidine hydrochloride and from it construct the
      denaturant binding polynomial and binding distribution function for the unfolded
      protein.

PMID- 12523653
TI  - News from the National Institute of General Medical Sciences: what is training in
      the pharmacological sciences?

PMID- 12523654
TI  - Application of DNA microarrays in pharmacogenomics and toxicogenomics.
AB  - Many drugs or xenobiotics can induce specific or nonspecific cellular signal
      transduction events that activate various physiologic and pharmacologic responses
      including homeostasis, proliferation, differentiation, apoptosis, and necrosis.
      To minimize the insults caused by these xenobiotics, tissues and organs are
      equipped with protective mechanisms that either pump drugs out of the cells
      (e.g., the multidrug-resistant, mdr, family of proteins) or increase the level of
      detoxifying enzymes such as phase I and II drug-metabolizing enzymes (DMEs),
      after exposure to xenobiotics. This review discusses the molecular analysis of
      pharmaco- or toxicogenomic gene expression profiles following exposure to cancer
      chemotherapeutic and chemopreventive agents. We present the development of DNA
      microarray technology and its use in expression profiling of possible signal
      transduction events elicited by these compounds, and its potential future
      applications in drug discovery and development in the pharmaceutical industry.

PMID- 12523655
TI  - Beta-adrenergic receptor polymorphisms: cardiovascular disease associations and
      pharmacogenetics.
AB  - The beta-adrenergic receptors (betaAR) play important roles in cardiovascular
      function and disease, and both agonists and antagonists are widely used in
      various settings for treatment of cardiovascular disease. Both the beta1AR and
      beta2AR genes have several polymorphisms that are common in the population and
      result in encoding of different amino acids. More importantly, in vitro
      functional studies suggest that these polymorphisms have functional significance.
      In this review we summarize the literature on the relationship between the betaAR
      polymorphisms and cardiovascular disease as well as the literature on the impact
      of these polymorphisms on drug response. Additionally, the polymorphisms in both
      the beta1AR and beta2AR genes are in linkage disequilibrium; thus, the relevance
      of single polymorphism vs. haplotype analysis is discussed. Further study of the
      betaAR genetic polymorphisms is likely to enhance our understanding of
      cardiovascular disease and improve our use of beta-agonists and beta-antagonists
      in treatment of cardiovascular disease.

PMID- 12523657
TI  - Locally delivered polyclonal antibodies potentiate intravenous antibiotic
      efficacy against gram-negative infections.
AB  - PURPOSE: Comparison of the anti-microbial efficacy of locally delivered
      antibodies in tandem with conventional systemic administration of ceftazidime
      antibiotic therapy in two lethal gram-negative animal infection models. METHODS:
      Previously published lethal E. coli-induced closed peritonitis and Klebsiella
      induced burn wound infections were generated in outbred female CF-1 mice cohorts.
      Pooled human polyclonal antibodies were injected locally into sites of infection
      in these mice simultaneously with intravenous infusions of the broad-spectrum
      antibiotic, ceftazidime. Mouse survival was compared in sham control cohorts vs.
      both ceftazidime-alone or antibody-alone systemically infused cohorts as well as
      local antibody-systemic ceftazidime combination therapy cohorts. Microbial
      burdens in blood and tissue samples (by agar plating), as well as interleukin-6
      cytokine levels (using ELISA) correlated with sepsis, were monitored in
      sacrificed animals as a function of antimicrobial treatment regimen. RESULTS:
      Local delivery of human polyclonal antibodies to infection sites was shown to
      produce synergistic therapeutic efficacy in combination with systemic antibiotic
      administration in these lethal wound infection models in mice. Enhanced benefits
      of the unique combination therapy included host survival, bacterial burden both
      locally and systemically, and IL-6 levels in host serum. CONCLUSIONS: Commercial
      pooled human antibodies contain a broad spectrum of antimicrobial activity
      against gram-negative pathogens. Prevention of systemization of infection
      correlates with host survival in these models. Local control of infection using
      doses of local, high-titer polyclonal antibodies can enhance traditional
      approaches to curb systemic spread of infection using intravenous antibiotics.
      Antibodies provide antimicrobial efficacy independent of known pathogen
      resistance mechanisms.

PMID- 12523658
TI  - Targeting efficiency of galactosylated liposomes to hepatocytes in vivo: effect
      of lipid composition.
AB  - PURPOSE: To investigate the effects of the lipid composition of galactosylated
      liposomes on their targeted delivery to hepatocytes. METHODS: Several types of
      liposomes with a particle size of about 90 nm were prepared using distearoyl-L
      phosphatidylcholine (DSPC), cholesterol (Chol) and cholesten-5-yloxy-N-(4-((1
      imino-2-D- thiogalactosylethyl)amino)butyl)formamide (Gal-C4-Chol), and labeled
      with [3H]cholesterol hexadecyl ether. Their tissue disposition was investigated
      in mice following intravenous injection. The binding and internalization
      characteristics were also studied in HepG2 cells. RESULTS: Compared with
      [H]DSPC/Chol (60:40) liposomes, [3H]DSPC/Chol/Gal-C4-Chol (60:35:5) liposomes
      exhibit extensive hepatic uptake. Separation of the liver cells showed that
      galactosylated liposomes are preferentially taken up by hepatocytes, whereas
      those lacking Gal-C4-Chol distribute equally to hepatocytes and nonparenchymal
      cells (NPC). Increasing the molar ratio of DSPC to 90% resulted in enhanced NPC
      uptake of both liposomes, suggesting their uptake via a mechanism other than
      asialoglycoprotein receptors. DSPC Chol/Gal-C4-Chol (60:35:5) and DSPC/Chol/Gal
      C4-Chol (90:5:5) liposomes exhibited similar binding to the surface of HepG2
      cells, but the former were taken up faster by the cells. CONCLUSIONS: The
      recognition of galactosylated liposomes by the asialoglycoprotein receptors is
      dependent on the lipid composition. Cholesterol-rich galactosylated liposomes,
      exhibiting less non-specific interaction and greater receptor-mediated uptake,
      are better for targeting drugs to hepatocytes in vivo.

PMID- 12523656
TI  - A ligand-based approach to understanding selectivity of nuclear hormone receptors
      PXR, CAR, FXR, LXRalpha, and LXRbeta.
AB  - In recent years discussion of nuclear hormone receptors, transporters, and drug
      metabolizing enzymes has begun to take place as our knowledge of the overlapping
      ligand specificity of each of these proteins has deepened. This ligand
      specificity is potentially valuable information for influencing future drug
      design, as it is important to avoid certain enzymes or transporters in order to
      circumvent potential drug-drug interactions. Similarly, it is critical that the
      induction of these same proteins via nuclear hormone receptors is avoided, as
      this can result in further toxicities. Using a ligand-based approach in this
      review we describe new and previously published computational models for PXR,
      CAR, FXR, LXRalpha, and LXRbeta that may help in understanding the complexity of
      interactions between transporters and enzymes. The value of these types of models
      is that they may enable us to design molecules to selectively modulate pathways
      for therapeutic effect and in addition predict the potential for drug
      interactions more reliably. Simultaneously, we might learn which came first: the
      transporter, the enzyme, or the nuclear hormone receptor?

PMID- 12523659
TI  - Pharmacokinetics and preventive effects of targeted catalase derivatives on
      hydrogen peroxide-induced injury in perfused rat liver.
AB  - PURPOSE: To investigate the pharmacokinetics and preventive effects of liver
      targeted catalase (CAT) derivatives on hepatic injury caused by reactive oxygen
      species. METHODS: The hepatic uptake of 111In-CAT, galactosylated (Gal-),
      mannosylated (Man-) and succinylated (Suc-) CAT was investigated in isolated
      perfused rat livers in a single-pass constant infusion mode. Then,
      pharmacokinetic parameters were obtained by fitting equations derived from a one
      organ pharmacokinetic model to the outflow profile. Their effects in preventing
      hydrogen peroxide-induced injury were determined by lactate dehydrogenase (LDH)
      release from the perfused liver. RESULTS: The extraction of CAT derivatives by
      the liver was dose-dependent, and increased by the chemical modifications
      described. After being bound to the cell surface, chemically modified CAT
      derivatives were internalized by the liver faster than CAT. Preperfusion of a CAT
      derivative significantly reduced LDH release by hydrogen peroxide at least for 30
      min, and Man-CAT and Suc-CAT effectively inhibited this release. CONCLUSIONS:
      Internalized CAT derivatives are also effective in degrading hydrogen peroxide
      and targeted delivery of CAT to liver nonparenchymal cells by mannosylation or
      succinylation is a useful method for the prevention of hepatic injury caused by
      reactive oxygen species.

PMID- 12523660
TI  - p-Aminohippurate transport at the apical membrane in the OK kidney epithelial
      cell line.
AB  - PURPOSE: We investigated the characteristics of transport of an organic anion, p
      aminohippurate (PAH), at the apical membrane in a kidney epithelial cell line OK.
      METHODS: Efflux and uptake of [14C]PAH across the apical membrane were measured
      using OK cell monolayers grown on microporous membrane filters. RESULTS: PAH
      efflux to the apical side was greater than that to the basolateral side and
      significantly inhibited by probenecid. Diethyl pyrocarbonate (DEPC), an inhibitor
      of potential-sensitive organic anion transport, significantly decreased PAH
      efflux to the apical side. Moreover, PAH efflux to the apical side was
      significantly decreased on incubation with high potassium buffer, as compared
      with control condition. Extracellular pH and Cl- had no effect on PAH efflux
      across the apical membrane. PAH uptake from the apical side was inhibited by
      various organic anions, and the inhibition patterns of PAH uptake from the apical
      and basolateral sides by various dicarboxylates were similar. CONCLUSIONS: These
      results suggested that PAH efflux to the apical side in OK cells was mediated by
      a potential-sensitive transport system, but not by an anion exchanger. Moreover,
      PAH uptake from the apical side was mediated by a specific transport system,
      which interacts with various organic anions and dicarboxylates.

PMID- 12523661
TI  - Multivariate statistics of disposition pharmacokinetic parameters for
      structurally unrelated drugs used in therapeutics.
AB  - PURPOSE: To explore the quantitative structure pharmacokinetic relationships of
      the disposition parameters: clearance (CL), apparent volume of drug distribution
      (V(ap)), fractal clearance (CL(f)), and fractal volume (v(f)) for 272
      structurally unrelated drugs used in therapeutics. METHODS: Literature data were
      used for CL and V(ap) whereas CL(f) and v(f) were estimated as described
      previously (Pharm. Res. 18, 1056, 2001 and 19, 697, 2002). A variety of molecular
      descriptors expressing lipophilicity, ionization, molecular size and hydrogen
      bonding capacity were estimated using computer packages. The data were analyzed
      using multivariate statistics. For each disposition parameter (CL, V(ap) CL(f),
      v(f)) PCA (principal component analysis) and PLS (projection to latent
      structures) were applied to the total set of data as well as to subsets of data.
      RESULTS: Drugs were divided into two classes (I and II) according to their
      v(f)/V(ap) ratio. Class I comprises 131 drugs with v(f)/V(ap) > 1, whereas class
      11141 drugs with v(f)/V(ap) < 1. After initial PLS analysis, class I was
      subdivided in subclusters I(a) (30 drugs) and I(b) (101 drugs). It was found that
      I(a) included mostly acidic drugs with high protein binding, whereas class II
      comprises mainly basic, lipophilic compounds. No correlation was found between
      CL, V(ap), CL(f) and the used descriptors. Adequate PLS models were derived for
      v(f) considering subclusters I(a), I(b) and class II separately. The low v(f)
      values of class I(a) drugs were affected negatively from molecular size
      descriptors and non-polar surface area. For class I(b) drugs with intermediate
      v(f) values, apparent lipophilicity contributed positively, although molecular
      size descriptors and polarity were inhibitory factors. The high v(f) values of
      class II drugs were positively dependent on intrinsic lipophilicity and increased
      basicity, whereas polarity entered with negative contribution. CONCLUSIONS: The
      parameters V(ap), CL, and CL(f) fail to reflect the physicochemical properties of
      drugs. The transformation of V(ap) values to v(f) is the underlying cause for the
      valid models for v(f). These models allow a global consideration of molecular
      properties (lipophilicity, ionization, molecular size, polar surface area) which
      govern the distribution of drugs in the human body. The present study provides
      additional evidence for the physiologically sound concept of v(f).

PMID- 12523662
TI  - Impact of omission or replacement of data below the limit of quantification on
      parameter estimates in a two-compartment model.
AB  - PURPOSE: To evaluate the influence of omission and replacement approaches for
      data below the limit of quantification (LOQ) on the estimation of pharmacokinetic
      parameters for two-compartment models when using nonlinear mixed-effect models.
      METHOD: Nine data sets were simulated according to a two-compartment intravenous
      bolus model with interindividual and residual variabilities, and a sparse
      sampling strategy was adopted. The data sets differed with respect to area-under
      the-curve (AUC) ratio (0.1. 0.2, 0.3) and half-life ratio (0.03, 0.1, 0.3)
      between the distribution and elimination phases. For each of the nine data sets,
      six reduced data sets were created by omitting 5%, 10%, 20%, 30%, 40%, or 50% of
      the lowest concentration values. For each of the reduced data sets only one
      simple correction procedure to handle observations below LOQ was applied. All the
      values below the LOQ were deleted, and the first one was replaced by half of the
      LOQ value. Population parameters were estimated for each of the 117 resulting
      data sets (one initial, six reduced, and six "corrected" data sets for each of
      the nine cases). This approach was also applied on a real data set of patients
      administered multiple i.v. bolus doses. RESULTS: For many of the data sets,
      particularly when a large fraction of the data was omitted, one or several
      population parameters were biased. When there was bias, clearance (CL) usually
      was underestimated, whereas peripheral volume was overestimated. The parameters
      related to the distribution phase (central volume and intercompartmental
      clearance) were less affected, and changes were not systematic. The correction
      procedure markedly decreased overall bias on the fixed effect of the parameters.
      Results for the real data were similar. CONCLUSION: Omission of data below the
      LOQ value may induce a not negligible bias on fixed-effect parameter estimates.
      The influence of the omission of values below LOQ was related to the underlying
      shape of the concentration-time profile and fraction of omitted observations. The
      use of a simple replacement rule seems to reduce this bias in estimates but needs
      further investigation.

PMID- 12523663
TI  - A theoretical analysis of low-frequency sonophoresis: dependence of transdermal
      transport pathways on frequency and energy density.
AB  - PURPOSE: Application of low-frequency ultrasound has been shown to increase skin
      permeability, thereby facilitating delivery of macromolecules (low-frequency
      sonophoresis). In this study, we seek to determine the dependence of transport
      pathways during low-frequency sonophoresis on ultrasound parameters. METHODS: Pig
      skin is exposed to low-frequency ultrasound over a range of frequencies to
      achieve different skin resistivities. The porous pathway model is used to study
      the dependence of average pore size, porosity, and tortuosity on ultrasound
      parameters. Imaging experiments are also carried out to visualize the transport
      pathways created by ultrasound. RESULTS: The data show that the average pore
      size, determined from the porous pathway model, does not depend on application
      frequency. Both in the presence and absence of ultrasound the average pore size
      determined from mannitol delivery is the same (28 +/- 12 A). With the application
      of ultrasound the skin porosity could be increased by up to 1700-fold. The effect
      of ultrasound on skin is heterogeneous thereby creating localized transport
      pathways (LTP). The porosity of these transport pathways is of the same order of
      magnitude as that of the dermis. CONCLUSIONS: With this study it is shown that
      low-frequency ultrasound increases skin permeability by increasing skin porosity
      rather than by increasing the size of the pores that are responsible for permeant
      delivery.

PMID- 12523664
TI  - Effects of sucrose and trehalose on the preservation of the native structure of
      spray-dried lysozyme.
AB  - PURPOSE: To investigate the effects of sucrose, trehalose, sucrose/ dextran
      mixtures, and sucrose/trehalose mixtures on the preservation of the native
      structure of spray-dried lysozyme in the solid state. METHODS: The intensity of
      the alpha-helical band and the melting enthalpies (deltaH(m)) of spray-dried
      lysozyme in the dried form and in aqueous solution were obtained using second
      derivative FTIR and differential scanning calorimetry (DSC) respectively.
      RESULTS: The intensity of the alpha-helical band and the deltaH(m) of spray-dried
      lysozyme obtained were linearly correlated and both suggest that the
      stabilization of lysozyme in the dried form was excipient concentration-dependent
      with a close to maximum stabilization being conferred by sucrose or trehalose at
      a mass ratio 1-2 (sugar:enzyme). Sucrose appeared to be more effective than
      trehalose on a weight by weight basis whilst stabilizing effects of
      dextran/sucrose or trehalose/ sucrose mixtures were found to be additive.
      CONCLUSION: Dehydration during spray drying was considered the main stress to the
      denaturation of lysozyme. A major effect of the sugars in protecting lysozyme
      against dehydration was attributable to hydrogen bonding between the sugar and
      protein molecules, which lead to an increase in the change in the negative value
      of the free energy between native and denatured states.

PMID- 12523665
TI  - Protective mechanism of stabilizing excipients against dehydration in the freeze
      drying of proteins.
AB  - PURPOSE: To investigate the influence of type and amount of excipient on the
      preservation of the native structure and the biologic activity of freeze-dried
      lysozyme and catalase. METHODS: The secondary structure of protein in the dried
      form and in aqueous solution was obtained using second derivative infrared
      spectroscopy and circular dichroism spectra respectively whilst the activity was
      determined using bioassay. RESULTS: Small molecular excipients (glycerol,
      sorbitol, 1,6-anhydroglucose, sucrose, and trehalose) were found to stabilize the
      activity and/or the native structure of freeze-dried lysozyme and catalase,
      despite the processing temperatures being above Tg' of excipent-protein mixtures.
      The preservation of catalase activity required excipient to be present at a lower
      excipient to enzyme mass ratio than that necessary to preserve native structure
      in the dried form. Combining dextran with sucrose synergistically protected the
      native structure of catalase but preserved the activity in an additive manner.
      CONCLUSION: The results indicate that the stabilization of catalase and lysozyme
      by excipients during dehydration was mainly due to water substitution rather than
      the formation of glass; the latter appearing not to be a prerequisite during
      freeze-drying.

PMID- 12523666
TI  - Independence of the product of solubility and distribution coefficient of pH.
AB  - PURPOSE: The relationship between the pH, solubility, and partition coefficient
      was investigated to show that the product of intrinsic values of solubility and
      partition coefficient is equal to the product of total values of solubility and
      distribution coefficient at different pH. METHODS: The pH distribution profiles
      were obtained from the literature and the pH solubility profiles were obtained
      from the literature or calculated from their intrinsic solubility and pK(a).
      RESULTS: The pH solubility and pH distribution coefficient profiles of 25
      compounds were investigated to show that the product of intrinsic solubility
      (S(w)) and intrinsic octanol-water partition coefficient (K(ow)) is equal to the
      product of total solubility of a partially ionized solute (ST) and its octanol
      buffer distribution coefficient (K(D)) at any pH where ion pair formation and
      salt precipitation are not present. CONCLUSIONS: The fact that S(w) x K(ow) can
      be used instead of S(T) x K(D) to model the absorption of partially ionized drugs
      in the gastrointestinal tract has important biopharmaceutical implications.

PMID- 12523667
TI  - Formation of fine drug particles by cogrinding with cyclodextrins. I. The use of
      beta-cyclodextrin anhydrate and hydrate.
AB  - PURPOSE: To improve the micromeritical properties of pranlukast (PRK) hydrate, a
      cogrinding process with cyclodextrin was used, and the formation of fine drug
      particles was investigated. METHODS: PRK crystals were ground with either beta
      cyclodextrin (beta-CD) anhydrate or beta-CD hydrate crystals at a mixing molar
      ratio of 2:1 (beta-CD:PRK) to prepare the ground mixtures (GMs). Powder X-ray
      diffraction measurement and particle size analysis were performed. RESULTS: The
      two GMs differed from one another in appearance, wettability, and fine particle
      production. Quantitative determination demonstrated that when the beta-CD
      hydrate/PRK GM was dispersed in water, 96% of PRK loaded in GM became fine
      particles smaller than 0.8 microm. In contrast, only 1.4% of PRK in GM
      transformed to fine particles in the case of beta-CD anhydrate/PRK GM. The PRK
      fine particles were considered to be dispersed as small crystals. The stability
      of PRK particles in the aqueous solution was improved by the addition of a water
      soluble polymer. CONCLUSION: Cogrinding with a beta-CD of higher water content
      can be an effective method to prepare fine drug particles at the submicron level.

PMID- 12523668
TI  - Enthalpy relaxation studies of celecoxib amorphous mixtures.
AB  - PURPOSE: The purpose of this study was to compare the structural relaxation and
      molecular mobility of amorphous celecoxib (CEL) with that of CEL amorphous
      mixtures consisting of various excipients and to study the effect of different
      excipients on the relaxation of high-energy amorphous systems. METHODS: The
      measurement of glass transition temperatures (Tg) and enthalpy relaxation were
      performed using differential scanning calorimetry. The interactions between drug
      and excipients and the absence of crystalline forms were further confirmed by
      conducting Fourier transform infrared spectroscopic and X-ray powder diffraction
      studies on same samples. RESULTS: All samples exhibited a single Tg value.
      Polymers had a prominent effect on the lowering of the relaxation rate in
      amorphous CEL. The lowering of the rate of relaxation was directly dependent on
      the concentration and type of polymer used. The total enthalpy required for
      relaxation was same, although additives affected the rate of relaxation.
      CONCLUSIONS: In absence of any specific interactions during Fourier transform
      infrared studies, it was concluded that the antiplasticizing activity of polymers
      is responsible for the stabilization of CEL amorphous systems. Glassy amorphous
      dispersions of CEL exhibited a complex type of relaxation pattern, which failed
      to fit in Kohlrausch-Williams-Watts equation with respect to calculation of
      relaxation time constants.

PMID- 12523669
TI  - The activation energy at Tg and the fragility index of indomethacin, predicted
      from the influence of the heating rate on the temperature position and on the
      intensity of thermally stimulated depolarization current peak.
AB  - PURPOSE: The purpose of this study was to estimate the activation energy at the
      glass transition temperature (and the fragility index) of amorphous indomethacin
      from the influence of heating rate on the features of the relaxation peaks
      obtained by thermally stimulated depolarization currents (TSDC) and to compare
      the obtained results with those obtained by other procedures based on TSDC data.
      METHODS: The glass transition temperature region of amorphous indomethacin was
      characterized at different heating rates by TSDC in a way similar to that used to
      determine the kinetics of the glass transition relaxation by differential
      scanning calorimetry. The features of a thermal sampled TSDC peak, namely the
      temperature location and the intensity, depend on the heating rate. RESULTS: The
      activation energy for structural relaxation (directly related to glass fragility)
      was estimated from the heating rate dependence of the TSDC peak location, T(m),
      and of the maximum intensity of the TSDC peak, I(T(m)). CONCLUSIONS: The methods
      for determining the activation energy for structural relaxation and fragility of
      indomethacin from TSDC data obtained with different heating rates were compared
      with other procedures previously proposed. TSDC, which is not a very familiar
      technique in the community of pharmaceutical scientists, proved to be a very
      convenient technique to study molecular mobility and to determine the fragility
      index in glass-forming systems. The value of approximately 60 appears as a
      reasonable value of the fragility index of indomethacin.

PMID- 12523670
TI  - A new mathematical model quantifying drug release from bioerodible microparticles
      using Monte Carlo simulations.
AB  - PURPOSE: The major objectives of this study were to 1) develop a new mathematical
      model describing all phases of drug release from bioerodible microparticles; 2)
      evaluate the validity of the theory with experimental data; and 3) use the model
      to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based
      microspheres. METHODS; 5-Fluorouracil-loaded microparticles were prepared with an
      oil-in-water solvent extraction technique and characterized in vitro. Monte Carlo
      simulations and sets of partial differential equations were used to describe the
      occurring chemical reactions and physical mass transport phenomena during drug
      release. RESULTS: The new mathematical model considers drug dissolution,
      diffusion with nonconstant diffusivities and moving boundary conditions, polymer
      degradation/erosion, time-dependent system porosities, and the three-dimensional
      geometry of the devices. In contrast with previous theories, this model is able
      to describe the observed drug release kinetics accurately over the entire period
      of time, including 1) initial "burst" effects; 2) subsequent, approximately zero
      order drug release phases; and 3) second rapid drug release phases. Important
      information, such as the evolution of the drug concentration profiles within the
      microparticles, can be calculated. CONCLUSIONS; A new, mechanistic mathematical
      model was developed that allows further insight into the release mechanisms in
      bioerodible microparticles.

PMID- 12523671
TI  - Dissolution rate enhancement by in situ micronization of poorly water-soluble
      drugs.
AB  - PURPOSE: The purpose of this study was to evaluate a novel in situ micronization
      method avoiding any milling techniques to produce nano- or microsized drug
      particles by controlled crystallization to enhance the dissolution rate of poorly
      water-soluble drugs. METHODS: Ibuprofen, itraconazole, and ketoconazole
      microcrystals were prepared by the association of the previously molecularly
      dispersed drug using a rapid solvent change process. The drug was precipitated in
      the presence of stabilizing agents, such as hydrocolloids. The obtained
      dispersion was spray-dried. Particle size, morphology, dissolution rate, specific
      surface area, and wettability were analyzed. Physicochemical properties were
      characterized using differential scanning calorimetry and X-ray diffractometry.
      RESULTS: The obtained dispersions showed a homogeneous particle size
      distribution. Drugs are obtained in a mean particle size of approximately 2
      microm and below. A high specific surface area was created and in situ
      stabilized. Different stabilizers showed differences in protecting the
      precipitated drug from crystal growth. The surface was hydrophilized because of
      the adsorbed stabilizer. Thus, a drug powder with markedly enhanced dissolution
      rate was obtained. CONCLUSIONS: In situ micronization is a suitable method for
      the production of micro-sized drugs. This technique can be performed continuously
      or discontinuously and uses only common technical equipment. Compared to milled
      products drug properties are optimized as all particle surfaces are naturally
      grown, the particle size is more uniformly distributed and the powder is less
      cohesive.

PMID- 12523672
TI  - Buccal transmucosal delivery of calcitonin in rabbits using thin-film composites.
AB  - PURPOSE: Salmon Calcitonin (sCT) is used to treat hypercalcemia resulting from
      Paget's disease and osteoporosis. sCT is available either in a sterile injectable
      form or nasal spray. Alternative and more cost-effective dosage forms for the
      delivery of calcitonin are needed. We sought to deliver sCT transmucosally using
      a previously reported mucoadhesive bilayer thin-film composite (TFC) via the
      buccal route. METHODS: Forty micrograms of salmon calcitonin (200-IU) was loaded
      on preformed TFCs. In vitro release of sCT from TFCs was monitored in phosphate
      buffered saline (10 mM, pH 7.4) at 37degrees C. Female New Zealand White rabbits
      (n = 6) were dosed with 40 microg of sCT either by injection via the ear vein or
      by applying sCT-loaded TFCs directly on the buccal pouch. Blood was collected at
      various times, and the plasma sCT and calcium concentrations were quantified.
      WinNonlin was used to determine the relevant pharmacokinetic parameters. RESULTS:
      In vitro, over 80% of sCT was released from the TFCs within 240 min. Super Case
      II transport was indicated as the primary release mechanism. Rabbits injected
      intravenously had C(max), Cls, Vss, and AUC(0-inf) values of 75.1 +/- 6.5 ng/mL,
      20.7 +/- 3.3 mL/min, 637 +/- 141 mL, and 1925 +/- 237 ng*min/mL, respectively.
      Rabbits dosed via the buccal route had C(max) Cls, and AUC(0-400 min values of
      4.6 +/- 1.6 ng/mL, 22.0 +/- 5.9 mL/min, and 842.9 +/- 209.7 ng*min/mL,
      respectively. The relative bioavailability for rabbits treated with the TFCs was
      43.8 +/- 10.9% with a CV of 24.9%. The reductions in plasma calcium levels after
      administration of sCT by both the intravenous and buccal route were comparable.
      CONCLUSIONS: The TFCs effectively delivered therapeutically efficacious amounts
      of sCT across the buccal mucosa in rabbits.

PMID- 12523673
TI  - Human, rat, and mouse metabolism of resveratrol.
AB  - PURPOSE: Resveratrol, a phenolic phytoalexin occurring in grapes, wine, peanuts,
      and cranberries, has been reported to have anticarcinogenic, antioxidative,
      phytoestrogenic, and cardioprotective activities. Because little is known about
      the metabolism of this potentially important compound, the in vitro and in vivo
      metabolism of trans-resveratrol were investigated. METHODS: The in vitro
      experiments included incubation with human liver microsomes, human hepatocytes,
      and rat hepatocytes and the in vivo studies included oral or intraperitoneal
      administration of resveratrol to rats and mice. Methanol extracts of rat urine,
      mouse serum, human hepatocytes, rat hepatocytes, and human liver microsomes were
      analyzed for resveratrol metabolites using reversed-phase high-performance liquid
      chromatography with on-line ultraviolet-photodiode array detection and mass
      spectrometric detection (LC-DAD-MS and LC-UV-MS-MS). UV-photodiode array analysis
      facilitated the identification of cis- and trans-isomers of resveratrol and its
      metabolites. Negative ion electrospray mass spectrometric analysis provided
      molecular weight confirmation of resveratrol metabolites and tandem mass
      spectrometry allowed structural information to be obtained. RESULTS: No
      resveratrol metabolites were detected in the microsomal incubations, and no phase
      I metabolites, such as oxidations, reductions, or hydrolyzes, were observed in
      any samples. However, abundant trans-resveratrol-3-O-glucuronide and trans
      resveratrol-3-sulfate were identified in rat urine, mouse serum, and incubations
      with rat and human hepatocytes. Incubation with beta-glucuronidase and sulfatase
      to release free resveratrol was used to confirm the structures of these
      conjugates. Only trace amounts of cis-resveratrol were detected, indicating that
      isomerization was not an important factor in the metabolism and elimination of
      resveratrol. CONCLUSION: Our results indicate that trans-resveratrol-3-O
      glucuronide and trans-resveratrol-3-sulfate are the most abundant metabolites of
      resveratrol. Virtually no unconjugated resveratrol was detected in urine or serum
      samples, which might have implications regarding the significance of in vitro
      studies that used only unconjugated resveratrol.

PMID- 12523674
TI  - Blood pressure measurement: a century of achievements and improvements in the
      year 2002.

PMID- 12523675
TI  - The angiotensin-receptor blockers: from antihypertensives to cardiovascular all
      round medications in 10 years?
AB  - Angiotensin-receptor blockers have been part of the antihypertensive treatment
      armamentarium since the mid-1990s. During this period, the number of agents has
      increased greatly, as has the number of indications for which these drugs are
      being tested in randomized controlled clinical trials. Beginning as efficacious
      and very well tolerated antihypertensives, angiotensin-receptor blockers have
      been shown to have benefits in patients with diabetes and heart failure that are
      not only attributable to the reduced blood pressure, as supported by recently
      concluded trials. The expanding treatment areas with these agents widen the
      interest in their applicability across the entire cardiovascular continuum. A
      number of large-scale studies set to report within the next few years will
      further determine the effects of angiotensin-receptor blockers in a range of
      cardiovascular indications beyond hypertension.

PMID- 12523676
TI  - The role of the critical event committee in a major cardiovascular outcome study.
AB  - Outcome studies in cardiovascular diseases such as hypertension are often based
      in a number of countries recruiting from multiple centres. This can lead to
      difficulties in end-point evaluation and classification. The INSIGHT study
      provided the unique opportunity to examine the role and usefulness of a Critical
      Event Committee (CEC) established to examine all events occurring in a cohort of
      6321 patients and classifying them according to pre-determined criteria. More
      than 28% of investigator-coded primary events and more than 41% of secondary
      events were re-classified by the CEC. Particularly difficult diagnoses included
      myocardial infarction, angina and heart failure, and the database finally
      analysed was substantially altered after CEC Committee evaluation. Post hoc
      analysis of the INSIGHT database demonstrated that the primary events compared
      would have been reduced from 6.3% vs 5.8% of those randomized on nifedipine vs co
      amilozide to 5.1% vs 4.7%--an overall reduction of 72 events of 382, a fall of
      18.8%. We conclude that a CEC should be a crucial component of any large outcome
      study and that if all events are subjected to scrutiny, the quality of the
      database is greatly enhanced.

PMID- 12523677
TI  - Impaired response to insulin associated with protein kinase C in chronic fructose
      induced hypertension.
AB  - A fructose-enriched diet induces an increase in blood pressure associated with
      metabolic alterations in rats. Our hypothesis was that an increase in protein
      kinase C (PKC) activation, reported in the acute period of fructose overload, and
      an impaired vessel's response to vasoactive substances contribute to maintain
      elevated blood pressure levels in the chronic period. The aims of this study were
      to investigate in this animal model of hypertension: (1) if the increase in PKC
      activation was also found in the chronic stage; (2) the involvement of nitric
      oxide and insulin in the vessel's response; and plasma atrial natriuretic factor
      and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the
      effects of: PKC-stimulator 12,13-phorbol dibutyrate, phenylephrine, insulin,
      nitric oxide synthase-inhibitor NG-nitro-L-arginine methyl esther (L-NAME) and
      PKC-inhibitor Calphostin C on aortic rings responses of Sprague-Dawley rats:
      fructose-fed and control. The fructose-fed group showed higher contractility to
      12,13-phorbol dibutyrate than the control group in aortic rings pre-incubated
      with insulin, and this difference disappeared with L-NAME. The response to
      phenylephrine in rings pre-incubated with Calphostin C was decreased in the
      fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats
      showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates
      than controls. In conclusion, chronic fructose feeding seems to develop an
      impaired response to insulin, dependent on nitric oxide, suggesting a PKC
      alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric
      oxide, would behave as compensatory mechanisms in response to high blood
      pressure.

PMID- 12523678
TI  - Cardiovascular risk in white-coat and sustained hypertensive patients.
AB  - We compared cardiovascular outcome between patients with white-coat and sustained
      hypertension who had previously participated in the Ambulatory Blood Pressure
      Monitoring and Treatment of Hypertension (APTH) trial. Baseline characteristics,
      including office and ambulatory blood pressure (BP), were measured during the 2
      month run-in period of the APTH trial. During follow-up, information on the
      occurrence of major cardiovascular events (death, myocardial infarction, stroke
      and heart failure), achieved office BP and treatment status was obtained. At
      entry, 326 patients had sustained hypertension (daytime ambulatory BP > or = 140
      mmHg systolic and/or > or = 90 mmHg diastolic) and 93 had daytime ambulatory BP
      below these limits and were classified as white-coat hypertensives. During 2088
      patient-years of follow-up (median follow-up 5.3 years), all major cardiovascular
      events (n = 22) occurred in the patients with sustained hypertension (rate 12.7
      per 1000 patient-years, p = 0.02 for between-group difference). Furthermore,
      multiple Cox regression confirmed that after adjustment for important
      covariables, daytime ambulatory BP--but not office BP at entry--significantly and
      independently predicted cardiovascular outcome. After additional adjustment for
      office BP, daytime ambulatory BP still predicted the occurrence of major
      cardiovascular events. Although white-coat hypertension was less frequently
      associated with antihypertensive drug treatment during follow-up, it carried a
      significantly better prognosis than sustained hypertension.

PMID- 12523679
TI  - Sources of measurement variation in blood pressure in large-scale epidemiological
      surveys with follow-up.
AB  - The Copenhagen City Heart Study (CCHS) is a longitudinal epidemiological study of
      19698 subjects followed up since 1976. Variation in blood pressure (BP)
      measurement in the first three CCHS surveys is evaluated by assessing two
      components, systematic variation and random variation [daytime and seasonally
      variation, observer bias, non-response bias, variation with explanatory
      variables, such as diabetes, hypertension, body mass index (BMI), height, plasma
      cholesterol and smoking] for the purpose of identifying relevant errors in
      population surveys. BP was measured in the seated position after a 5 min rest,
      with the cuff around the non-dominating arm, in accordance with recommended
      guidelines. The participation rate fell from 74% in survey 1 to 63% in survey 3.
      Significant non-response bias with respect to BP values was not found. No daytime
      variability was noted either in systolic (SBP) or diastolic (DBP) BPs. A trend
      towards a lower BP was seen during the summertime. Random variation, expressed as
      the standard deviation of the measured values, increased with increasing BP
      values (SBP: 11.9-13.4 to 21.2-25.1 mmHg; DBP: 10.6-11.2 to 11.9-13.4 mmHg). SBP
      was positively correlated to BMI and plasma cholesterol. SBP was 5-10 mmHg higher
      in diabetics (p = 0.000-0.04) than in age- and sex-matched non-diabetics. DBP did
      not differ between the two groups. Smokers from the age of 50 years had a 2-4
      mmHg lower SBP (p = 0.000-0.01) and 1-3 mmHg lower DBP (p = 0.000-0.005) than had
      non-smokers. In addition, significantly fewer smokers took antihypertensive
      medication than did non-smokers (p = 0.000). In conclusion, judging from the
      degree of association with BP and/or differences between the three surveys, the
      most important factors to consider were seasonal variation, BMI, the use of
      antihypertensive drug therapy, plasma cholesterol, smoking status and diabetes.
      An inter-survey comparison of BP in population cohorts requires controlling for
      these factors.

PMID- 12523680
TI  - Early versus late morning measurement of blood pressure in healthy men. A
      potential source of measurement bias?
AB  - Standardization of blood pressure (BP) measurement is important for both clinical
      and epidemiological purposes. The aim of the present study was to investigate
      early vs late morning measurements of BP and heart rate in healthy subjects.
      During the years 1972-75, healthy men aged 40-59 years (n = 2014) participated in
      a cardiovascular survey in Oslo. Two to four men underwent the examination
      program per day; it included height/weight, a spirographic study, chest X-ray, a
      number of blood tests, case history, clinical examination, resting ECG and
      physical exercise testing. BP and heart rate measurements were meticulously
      standardized. When adjusting for age, smoking habits and season of year we found
      that men who were examined as number one in the row of two to four subjects each
      morning had higher systolic BP (3.6 mmHg, p < 0.001) and heart rate (3.6
      beats/min, p < 0.001) at rest compared to others. They were virtually identical
      in all other aspects. These differences in systolic BP and heart rate at rest
      disappeared during bicycle exercise. Thus, we suggest that the increased BP and
      heart rate at rest represent a stress reaction to being number one in a row of
      subjects to be examined, i.e. a bias in BP and heart rate measurements, possibly
      of both clinical and epidemiological importance.

PMID- 12523681
TI  - Comparison of home and office blood pressure in treated hypertensives in the
      Nordic Diltiazem (NORDIL) Study.
AB  - The aim of the Nordic Diltiazem (NORDIL) Study was to compare cardiovascular
      morbidity and mortality in calcium-antagonist-based treatment with diltiazem and
      conventional diuretic/beta-blocker-based treatment in essential hypertension. The
      objective of the present sub-study was to compare self-measured home blood
      pressure with office blood pressure at a time-point in the study when the
      patients' blood pressures had been treated to the level that the investigators
      conceived to be the blood pressure target. The NORDIL study was prospective,
      randomized, open and endpoint-blinded. It enrolled 10881 patients aged 50-74
      years at health centers in Norway and Sweden who had diastolic blood pressure
      (BP) of 100 mmHg or more. The present sub-study group (n = 87) was small but
      fairly representative for the entire study population regarding baseline
      characteristics. Both systolic (4.0 mmHg, p = 0.01) and diastolic blood pressures
      (3.1 mmHg, p < 0.001) were significantly lower at home than in the office.
      Pearson correlation coefficients between the respective office and home readings
      were statistically highly significant (p < 0.001), but of moderate strength
      ranging from r = 0.41 for heart rate to r = 0.46 and r = 0.58 for diastolic and
      systolic blood pressures, respectively. Altman plots also gave statistical
      support to some inconsistency between the two methods of measurements. Pearson
      correlation coefficients between afternoon and morning measurements showed strong
      relationships with r-values >0.9 for both blood pressures and heart rate. The
      Altman plots also suggested excellent consistency between afternoon and morning
      measurements. Thus, motivated and trained hypertensive patients can perform home
      recordings of blood pressure and heart rate with precision; however, there are
      differences between recordings at home and in the investigators' offices that
      suggest some degree of "white coat effect" in these treated hypertensives.

PMID- 12523682
TI  - Lower plasma noradrenaline and blood viscosity on carvedilol vs atenolol in men
      with recent myocardial infarction.
AB  - The Carvedilol Acute Myocardial Infarction Study (CAMIS) investigates cardiac
      remodeling in patients (n = 250) randomized to carvedilol vs atenolol and treated
      for 12 months after acute myocardial infarction. In a sub-study, we compared
      sympathetic, hemorrheological and vascular effects in small but particularly well
      matched groups of participants who had been on reasonably equipotent but
      unchanged doses of carvedilol (n = 10) or atenolol (n = 10) for at least 4 weeks.
      Blood pressures (p < 0.05), plasma adrenaline (p = 0.034), plasma vasopressin (p
      = 0.022) and whole blood viscosity at shear rate 0.5 cp (p = 0.050), 1.1 cp (p =
      0.023), 5.8 cp (p = 0.049) and 201 cp (p = 0.060) taken in the laboratory at
      baseline before 2 h of using the hyperinsulinemic, isoglycemic glucose clamp were
      lower on carvedilol. Plasma noradrenaline was lower on carvedilol at baseline and
      throughout the clamp (p < 0.0005). Forearm vascular resistance as measured by
      plethysmography during the clamp tended to be lower on carvedilol (p = 0.074). No
      significant difference was found between the groups in glucose disposal rate
      measured by clamp, maximal forearm blood flow and minimal forearm vascular
      resistance after 10 min of ischemia, or in ambulatory blood pressure and heart
      rate taken a few days later. Thus, potential benefits of carvedilol vs atenolol
      were seen in these post-infarction patients in a laboratory setting. These
      findings suggest that the inhibitory effects on the sympathetic nervous system
      and related blood viscosity are stronger with carvedilol than with atenolol.

PMID- 12523683
TI  - Foot and mouth disease: facing the new dilemmas.

PMID- 12523684
TI  - Review of the status of foot and mouth disease in countries of South America and
      approaches to control and eradication.
AB  - Since the signing in 1987 of the Hemispheric Plan for the Eradication of Foot-and
      Mouth Disease (PHEFA) by the countries of South America, clinical cases of foot
      and mouth disease (FMD) have decreased significantly throughout the continent.
      During the early 1990s, national laboratories diagnosed an average of 766 cases
      per year in South America. By the late 1990s, this continent-wide average had
      fallen to 130. By the end of the 1990s, the international community recognised
      Argentina, Chile, Guyana and Uruguay as free of FMD without vaccination. In 1999,
      clinical signs of FMD were absent in 60% of all cattle of the continent. These
      cattle represented 41% of all herds in South America and extended over 60% of the
      geographical area of the continent. However, in the spring of 2001, FMD re
      appeared in certain countries of the Southern Cone. This widespread re-occurrence
      of the disease in Argentina, Uruguay and the State of Rio Grande do Sul in Brazil
      called into question the basic premise of the PHEFA--that countries in South
      America can achieve and maintain FMD-free status, with or without vaccination.
      The authors suggest that these countries can regain their FMD-free status by
      supporting the PHEFA. A successful disease eradication strategy relies on high
      levels of vaccination, effectiveness of outbreak responses, and control of animal
      movement. This strategy must have a regional, not national, focus and must be
      based on risk analysis methodology. The multilateral administration of
      vaccination campaigns and field activities to ensure wide and simultaneous
      vaccine application, along with primary prevention and joint border activities,
      is the key to eradicating FMD and maintaining areas free of the disease.

PMID- 12523685
TI  - Review of the status and control of foot and mouth disease in sub-Saharan Africa.
AB  - Six of the seven serotypes of foot and mouth disease (FMD) virus (i.e. all but
      Asia 1) are prevalent in Africa although there are marked regional differences in
      distribution. Three of these serotypes are unique to Africa, namely the three
      South African Territories (SAT) serotypes. Serotype C may also now be confined to
      Africa because it has not been reported elsewhere recently. In southern Africa at
      least, the SAT serotypes have an intimate and probably ancient association with
      African buffalo (Syncerus caffer) that is instrumental in their maintenance.
      Within each of the six prevalent serotypes, with the possible exception of C,
      there are a number of different lineages with more or less defined distributions
      (i.e. topotypes) that in some cases are sufficiently immunologically different
      from one another to require specific vaccines to ensure efficient control. This
      immunological diversity in prevalent serotypes and topotypes, in addition to
      uncontrolled animal movement in most parts of the continent, render FMD difficult
      to control in present circumstances. This fact, together with poorly developed
      intercontinental trade in animals and animal products has resulted in the control
      of FMD being afforded a low priority in most parts of the continent, although the
      northern and southern regions of the continent are an exception. As a
      consequence, eradication of FMD from Africa as a whole is not a prospect within
      the foreseeable future. In southern Africa, the use of fencing and other means to
      strictly control the movement of wildlife and livestock as well as judicious
      application of vaccine has resulted in countries of the region being able to
      access beef and other livestock markets in Europe and elsewhere in the developed
      world. Significant marketing of livestock and livestock products from Africa
      outside the continent is unlikely to be achieved unless similar approaches can be
      developed for other regions of Africa. This will result in continuing under
      exploitation of a valuable resource in the arid and semi-arid regions of Africa,
      with increasing marginalisation of human populations living there.

PMID- 12523686
TI  - Regional status and approaches to control and eradication of foot and mouth
      disease in the Middle East and North Africa.
AB  - The Middle East is regarded as the region of the world most heavily affected by
      foot and mouth disease (FMD). The situation in the Middle East and North Africa
      constitutes a threat to other regions of the world, especially Europe. Risk
      management differs between North Africa and the Middle East due to different
      epidemiological situations. In the Middle East, the national cattle population is
      the principal target of preventive vaccination. Vaccination is used as a tool for
      preventing economic losses due to the disease, rather than as a means to prevent
      the spread of the infection. In North Africa, as FMD occurs almost cyclically,
      management is more focused on emergency preparedness and limitation of the spread
      of the disease upon diagnosis, as well as on effective control measures based on
      quarantine and mass vaccination. To reduce future outbreaks of FMD in the
      countries of the two regions, a common strategic programme should be adopted,
      based on effective regional co-operation at many levels. This should be
      complemented by efforts to restructure and consolidate the national Veterinary
      Services.

PMID- 12523687
TI  - Recent outbreaks of foot and mouth disease in countries of east Asia.
AB  - Japan regained the status of freedom from foot and mouth disease (FMD) without
      vaccination in September 2000 and the Republic of Korea likewise obtained this
      status in September 2001. However, new outbreaks of FMD caused by the pan-Asian
      topotype have occurred in pigs in the Republic of Korea since May 2002. Taipei
      China has not experienced an outbreak of FMD since February 2001 and the country
      is currently implementing an eradication programme. These countries had been free
      from FMD for many decades when in 1997, the FMD virus (FMDV) once again invaded
      the region, particularly in 2000; this resulted in widespread occurrence of the
      disease. The types of FMDV were investigated by genome analysis, and in each case
      the virus concerned was found to be a member of the pan-Asian O lineage. The
      authors present the recent situations and the characteristics of FMD in countries
      of east Asia.

PMID- 12523688
TI  - Review of the status of foot and mouth disease and approach to
      control/eradication in Europe and Central Asia.
AB  - The authors describe the situation of foot and mouth disease (FMD) in Europe over
      the past 70 years and analyse the origin of the disease and methods of control,
      particularly since preventive vaccination was banned in Europe in the early
      1990s. Since then, and until 2001, despite several incursions of the virus, the
      disease has always been contained and eradicated rapidly. Therefore, the ban on
      vaccination did not result in an increase of FMD outbreaks. However, the massive
      outbreak which took place in 2001 in the United Kingdom (UK) with 2,030
      outbreaks, raised questions on the policy utilised to date to control the disease
      in Europe. In future, the utilisation of ring vaccination should be considered as
      an alternative to mass culling of large numbers of animals. Based on the recent
      source of introduction of the virus, the authors review the lines of defence
      which should be reinforced to reduce the risk of further introduction of the
      disease. The FMD situation in the Commonwealth of Independent States (CIS) is
      also examined. The situation in the Central Asian Republics and the Caucasian
      region deteriorated after the collapse of the Soviet Union, despite the
      continuous effort of Russia to support these countries. International support is
      needed to prevent FMD from becoming endemic in the region.

PMID- 12523689
TI  - Risk management of international trade: emergency preparedness.
AB  - Emergency preparedness and management are among the most important and critical
      issues facing animal health in the world today. The goals of a country for an
      animal health emergency management (AHEM) system should include the following: -
      being prepared to detect and manage an outbreak of a foreign animal disease -
      preventing the introduction of foreign and emerging animal pathogens --having an
      appropriate response system for control and eradication of the disease --having a
      system for recovery from animal health emergencies, including natural disasters.
      An AHEM system can no longer be limited to a single organisation within a
      country. In the event of a serious threat to the animal agriculture of a country,
      broader and more comprehensive participation is required. If not properly planned
      for, animal health emergencies can rapidly become national disasters. Therefore,
      it is essential that the central government of a country work towards these goals
      through partnerships with other Federal and State/Provincial/District
      organisations, academic institutions and national animal industries.

PMID- 12523690
TI  - Clinical variation in foot and mouth disease: cattle.
AB  - Foot and mouth disease (FMD) in cattle is usually clinically obvious in the
      unvaccinated herds of countries in which the disease occurs only occasionally.
      However, in vaccinated herds and in some breeds indigenous to areas in which FMD
      is endemic, the disease may circulate undetected.

PMID- 12523691
TI  - Clinical variation in foot and mouth disease: sheep and goats.
AB  - Foot and mouth disease (FMD) in adult sheep and goats is frequently mild or
      unapparent, but can cause high mortality in young animals. The recent outbreak of
      FMD in the United Kingdom has highlighted the importance of sheep in the
      epidemiology of the disease, although there have been numerous examples in the
      past where small ruminants have been responsible for the introduction of FMD into
      previously disease-free countries. The difficulty in making a clinical diagnosis
      should encourage the development of more rapid screening tests to assist in
      future control programmes.

PMID- 12523692
TI  - Clinical variation in foot and mouth disease: pigs.
AB  - In intensively reared pigs, the introduction of foot and mouth disease (FMD)
      results in severe clinical disease and vesicular lesions in adult and fattening
      animals, and high mortality in piglets. Vaccination of uninfected herds can
      assist FMD control and eradication programmes by reducing susceptibility of pigs
      older than 12 to 14 weeks and providing early protection to piglets through
      maternal antibody, but once FMD is established on a farm, vaccination alone will
      not prevent recurrent outbreaks of clinical disease.

PMID- 12523693
TI  - Unapparent foot and mouth disease infection (sub-clinical infections and
      carriers): implications for control.
AB  - Unlike animals which are carriers of foot and mouth disease (FMD), sub-clinically
      infected animals may be highly contagious. The implications of sub-clinical
      infections for the control of FMD are serious because such animals are likely to
      disseminate the disease when in contact with susceptible livestock. Recent
      dissemination of FMD virus (FMDV) in Europe shows that sub-clinically infected
      animals render trade in animals or animal products a potential risk for importing
      countries. This clearly demonstrates that the paradigm 'free of FMD without
      vaccination' is not synonymous with 'risk-free'. The risk of introduction of
      subclinical FMD into FMD-free countries may increase significantly, with the
      occurrence of large susceptible animal populations, changed agricultural
      practices, expansion of trade in live animals and animal movements, increased
      trade in animal products and greater mobility of people. Such changes in
      circumstances require that national and international authorities remain
      continuously vigilant to determine any altered risk for importation of FMD. A few
      historical reports and some recent observations in southern Africa indicate the
      possibility of dissemination of FMD by bovine carriers into herds of susceptible
      cattle. These reports have greatly influenced FMD trade policies and thus, FMD
      control and eradication strategies. However, other field evidence does not
      support this claim and several controlled experiments were unable to show that
      carriers are able to initiate disease. When millions of cattle were
      systematically vaccinated with good quality vaccines, FMD disappeared in spite of
      a large sentinel population in the form of calves and unvaccinated sheep and
      pigs. A low number of carriers most likely persisted, but they did not hamper the
      eradication of the disease. Vaccination policies and trade regulation must be
      based on risk assessments taking these factors into consideration.

PMID- 12523694
TI  - Identification of foot and mouth disease virus carrier and subclinically infected
      animals and differentiation from vaccinated animals.
AB  - Countries that are free of foot and mouth disease (FMD) are reluctant to use
      vaccine in the event of an outbreak because of the difficulties this can cause in
      re-establishing freedom from FMD status to the satisfaction of trading partners.
      The problem does not lie in distinguishing between vaccinated and recovered
      animals as vaccinated animals can be tagged or otherwise marked to show that they
      have been vaccinated; the difficulty is in identifying vaccinated animals that
      have had contact with live virus and become carriers. The traditional probang
      test is not sufficiently sensitive and is labour- and laboratory-intensive, but
      alternative serological tests such as those for antibodies to non-structural
      proteins (NSPs), or specific immunoglobulin A (IgA) are also not 100% sensitive.
      However, these newer tests do provide increased security by reducing the
      likelihood of trading carrier animals and can be used to help define the limits
      of an outbreak; the use of vaccine to help control an outbreak of FMD in a
      previously free country still has significant consequences on trade in FMD
      susceptible animals and their products.

PMID- 12523695
TI  - How predictable were the outbreaks of foot and mouth disease in Europe in 2001
      and is vaccination the answer?
AB  - The author raises three important questions on the outbreaks of foot and mouth
      disease (FMD) in Europe in 2001: were these linked to stopping preventive
      vaccination, could these outbreaks have been forecast and were they avoidable,
      and is vaccination an efficient tool to control outbreaks? The replies to these
      questions are based on recent history of FMD in Europe. The author demonstrates
      that the 2001 outbreaks were not linked to ceasing vaccination in Europe in 1991.
      He also attempts to understand the reasons which encouraged the United Kingdom
      not to use vaccination to halt the progression of the disease, despite the clear
      demonstration that vaccination is a useful tool in arresting the spread of an
      epidemic. In conclusion, the author suggests that substantial changes to European
      policy for FMD control used for the past ten years are not necessary, but that
      recourse to emergency vaccination should be considered as an important control
      option in the future. This option should be optimised by ensuring that
      differential serological tests are performed in parallel with emergency
      vaccination, thereby enabling the identification and subsequent elimination of
      infected herds.

PMID- 12523696
TI  - Decision-support tools for foot and mouth disease control.
AB  - Recent experience with foot and mouth disease (FMD) has shown that large and very
      costly epidemics can occur in countries considered extremely unlikely to
      experience the disease. The consequences of an introduction are much more severe
      than in the past and effective control is more difficult to achieve. Few
      countries have developed effective risk management strategies and information
      based response systems to respond to these developments. The authors describe the
      tools which can be employed to minimise the impact of a disease incursion, using
      the example of FMD. To make such systems effective, the development of a national
      farms database in advance, including geo-referencing, is highly desirable. This
      greatly enhances the power of the decision-support tools, which can then be
      applied as soon as a serious disease incursion has been detected. These tools
      include procedures to detect infected farms promptly, to protect as yet
      uninfected farms against exposure to virus and to manage control policies.
      Epidemiological evaluation and prediction tools have advanced particularly
      rapidly and can guide the choice of control policies during an outbreak.
      Integrated decision-support systems offer the best method of managing FMD
      outbreaks to minimise the cost and size of the epidemics.

PMID- 12523697
TI  - Predicting the spread of foot and mouth disease by airborne virus.
AB  - Foot and mouth disease (FMD) can spread by a variety of mechanisms which, under
      certain climatic and epidemiological conditions, includes the windborne spread of
      disease. Recent advances in knowledge of the aerobiological features of FMD are
      described. The strain of virus and species of infected animal are major
      determinants of airborne virus emission. Pigs emit most virus, cattle and sheep
      lesser but similar amounts to each other. Peak excretion of airborne virus by
      sheep occurs before the clinical phase of disease, whereas with cattle and pigs,
      it coincides with the development of early clinical disease. The probability of
      aerogenous infection differs greatly between livestock species. Cattle are the
      most susceptible, followed by sheep, whereas pigs are very resistant. Computer
      based simulation models have been developed to analyse and predict the risk of
      airborne spread of FMD and have been used successfully during outbreaks to
      support decision-making. Further research is required to refine and extend the
      models for operational use.

PMID- 12523698
TI  - Development and performance of inactivated vaccines against foot and mouth
      disease.
AB  - The historical background of foot and mouth disease (FMD) vaccine production is
      briefly described. Improvements achieved through the use of monolayer and
      suspension cultures are outlined. Elements that are crucial in the production of
      modern vaccines are discussed, such as inactivation of viral antigen, successive
      concentration and purification of the antigen and the final formulation of the
      vaccine. Storage of concentrated antigen at ultra-low temperatures creates
      greater flexibility for the producer and has also enabled national and
      international organisations to establish vaccine banks. The purification of FMD
      viral antigens, including the removal of non-structural proteins (NSPs), enables
      the immune responses of vaccinated animals to be distinguished from the responses
      of animals infected with live FMD virus. Consequently, the combined use of
      purified vaccine and tests for the detection of antibodies against NSPs
      essentially provides a marker system to distinguish between vaccinated animals
      that subsequently become infected and those that have not. Bearing in mind the
      good record of modern vaccines in the control of outbreaks and the possibility of
      screening vaccinated herds for carriers, the author proposes that the OIE
      reconsider the differences between the requirements for regaining export status
      following the use of stamping-out as opposed to vaccination in outbreak
      situations.

PMID- 12523699
TI  - Prospects, including time-frames, for improved foot and mouth disease vaccines.
AB  - Inactivated foot and mouth disease (FMD) vaccines have been used successfully as
      part of eradication programmes. However, there are a number of concerns with the
      use of such vaccines and the recent outbreaks of FMD in disease-free countries
      have increased the need for improved FMD control strategies. To address this
      requirement, new generation FMD vaccines are being developed. Currently, one of
      the most promising of these vaccine candidates utilises an empty viral capsid
      subunit delivered to animals by a live virus vector. This candidate, a
      replication-defective recombinant human adenovirus containing the capsid and 3C
      proteinase coding regions of FMD virus (FMDV), induces an FMDV-specific
      neutralising antibody response in inoculated animals. Upon challenge with a
      virulent animal-passaged homologous virus, swine and cattle vaccinated with this
      recombinant adenovirus are protected from clinical signs of FMD as well as from
      FMDV replication. One inoculation of a high dose of this vaccine candidate
      protected swine from challenge as early as seven days after vaccination.

PMID- 12523700
TI  - Foot and mouth disease: the future of vaccine banks.
AB  - The authors briefly review the history of vaccine banks for foot and mouth
      disease, their current location and their constituent serotypes and strains,
      together with the occasions on which they have been activated. Experimental
      studies on emergency vaccines are summarised and areas identified for further
      investigation. The future of such banks is considered, including the principal
      strengths and weaknesses of existing banks, and suggestions are made for
      potential improvements. The fact that the banks have been activated on relatively
      few occasions over the 25 years of their existence testifies in part to the
      relatively rare calls which have been made upon them, but also reflects the
      difficulty in deciding when and how to utilise emergency vaccination.
      Nevertheless, in an era of increasing global risks of the spread of foot and
      mouth disease, banks will most certainly continue to have strategic and tactical
      importance in the control of this most readily communicable of animal diseases.

PMID- 12523701
TI  - Use of vaccination against foot and mouth disease in zoo animals, endangered
      species and exceptionally valuable animals.
AB  - A historical review of foot and mouth disease (FMD) in non-domestic species is
      given and the use of FMD vaccines to protect those species is described. Several
      non-domestic species are susceptible to FMD. Legislation in many countries, based
      on the definition of FMD-free status as determined by the Office International
      des Epizooties (OIE: World organisation for animal health), forms an important
      barrier against the use of vaccines. National authorities may even feel obliged
      to slaughter animals of threatened species protected by international agreements
      during an outbreak of FMD to preserve their FMD-free status. The importance of
      international breeding programmes for endangered species is forcing the
      international community to reconsider the role that vaccination against FMD
      should play in animal health prevention programmes of captive populations. Much
      research is still required in regard to vaccine types and diagnostic procedures.
      Species-specific differences in susceptibility to FMD make this a challenging
      research topic for zoological institutions.

PMID- 12523702
TI  - Economic aspects of foot and mouth disease: perspectives of a free country,
      Australia.
AB  - Australia is a significant livestock producer and a major exporter of livestock,
      livestock products and livestock genetic material. An outbreak of foot and mouth
      disease (FMD) would have severe economic consequences on the economy. A recent
      study found that in an outbreak lasting six months, real gross domestic product
      in Australia would fall by an estimated 0.6% (AUS$3.5 billion), employment by
      0.8%, and a depreciation of 3% would be recorded in the exchange rate in the
      first year. Much of this impact would be due to the loss of export markets. Given
      the significant consequences of an outbreak of FMD, Australia invests
      considerable resources in prevention and planning. These measures can be viewed
      at three levels, namely: pre-border, border and post-border. Australia recently
      further enhanced quarantine at the border to minimise the risk of entry of FMD.
      However, no matter how much is invested, there is no guarantee that FMD will not
      enter the country. Accordingly, it is important to ensure that comprehensive
      contingency plans are also in place. Recent outbreaks in previously free
      countries have shown that a large outbreak of FMD poses major problems for the
      animal health services of a country and a combined government and industry
      response is required.

PMID- 12523703
TI  - The economics of foot and mouth disease.
AB  - The economic effects of foot and mouth disease (FMD) are summarised. Losses arise
      from the direct effects of the disease on production, costs of disease control
      and restriction of trade. Direct effects are of greatest importance in dairy and
      pig production systems. Costs of disease control, whether by stamping-out or
      vaccination are high. Even countries that are free of the disease incur
      prevention and emergency preparedness costs. The published studies indicate that
      where FMD eradication is feasible, this is the least-cost policy option, even
      allowing for the costs of prevention, emergency preparedness and the risk of
      outbreaks. Where eradication is not feasible, it is economically beneficial to
      protect high-producing livestock by vaccination. Vaccination of lower-producing
      animals may also be justified, especially where these animals produce milk or
      traction power, or where this would serve to protect high-producing livestock
      from disease challenge.

PMID- 12523704
TI  - The economic impact of foot and mouth disease control and eradication in the
      Philippines.
AB  - The authors evaluate the impact of foot and mouth disease (FMD) and control of
      the disease in the Philippines using cost-benefit analysis. A scenario in which
      FMD control is maintained at recent levels with continued presence of the disease
      is compared to scenarios in which a publicly funded programme achieves
      eradication by 2005 (current policy objective), 2007 and 2010. Under varying
      assumptions regarding the development of exports of livestock products following
      eradication, estimated benefit-cost ratios for the investment in eradication
      range from 1.6 (2010, no exports) to 12.0 (2005, export of 5,000 tons each of low
      value and high-value livestock products annually), indicating eradication to be
      an economically viable investment. The commercial swine sector is estimated to
      capture 84% of the benefits generated by the public investment in eradication,
      versus 4% by backyard swine producers. The implications of these results within
      the context of regional efforts to control FMD in South-East Asia are explored.

PMID- 12523705
TI  - The dynamics and impact of foot and mouth disease in smallholder farming systems
      in South-East Asia: a case study in Laos.
AB  - There is a general lack of data on the different patterns of dynamics and impact
      of foot and mouth disease (FMD) in South-East Asia and the impact the disease has
      on different sectors, in particular the smallholder sector in which livestock
      play such an important role. A pilot study was conducted of a recent outbreak of
      FMD that swept across the southern part of Laos during the second half of 1999.
      The main objectives of the study were to investigate the possible routes of
      transmission of the disease and the impact of FMD on the predominantly
      smallholder rice/livestock production system of Savannakhet Province. The study
      was performed by group interviews of farmers in ten villages, located in five
      districts across the width of the Province, and of district and provincial
      veterinary officials. Results suggested that the infection had probably been
      introduced from the eastern border and had spread rapidly west, along a principal
      trading route of pigs, cattle and buffalo. In the process, many villages adjacent
      to this trading route became infected and the disease spread rapidly within
      infected villages. The disease had a significant impact on the agricultural
      system, but the impact would have been much greater had the epidemic occurred
      during the season of paddy field preparation. Mortality was observed in young
      buffalo, cattle and pigs, and long periods of morbidity were observed in buffalo,
      often requiring extended treatment. The sale of livestock for cash was severely
      restricted, creating additional repercussions on that sector. It was concluded
      that the most appropriate approach to FMD control would be to prevent infected
      animals from entering the principal trading routes for pigs, cattle and buffalo.
      This will require the involvement of all the stakeholders of the livestock
      industry, including traders and veterinary authorities. A further tactic to be
      considered would be to protect livestock systems adjacent to these trading routes
      by vaccination. An economic study of the market incentives of both traders and
      smallholders is recommended and this approach is advocated in other parts of
      South-East Asia where livestock trading routes present the major risk of FMD
      outbreaks.

PMID- 12523706
TI  - Economic costs of the foot and mouth disease outbreak in the United Kingdom in
      2001.
AB  - The authors present estimates of the economic costs to agriculture and industries
      affected by tourism of the outbreak of foot and mouth disease (FMD) in the United
      Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to
      about Pound Sterling3.1 billion. The majority of the costs to agriculture have
      been met by the Government through compensation for slaughter and disposal as
      well as clean-up costs. Nonetheless, agricultural producers will have suffered
      losses, estimated at Pound Sterling355 million, which represents about 20% of the
      estimated total income from farming in 2001. Based on data from surveys of
      tourism, businesses directly affected by tourist expenditure are estimated to
      have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2
      billion) as a result of reduced numbers of people visiting the countryside. The
      industries which supply agriculture, the food industries and tourist-related
      businesses will also have suffered losses. However, the overall costs to the UK
      economy are substantially less than the sum of these components, as much of the
      expenditure by tourists was not lost, but merely displaced to other sectors of
      the economy. Overall, the net effect of FMD is estimated to have reduced the
      gross domestic product in the UK by less than 0.2% in 2001.

PMID- 12523707
TI  - Control of foot and mouth disease: the experience of the Americas.
AB  - Foot and mouth disease (FMD) was first recognised in South America in 1870,
      almost simultaneously in the province of Buenos Aires (Argentina), in the central
      region of Chile, in Uruguay, in southern Brazil and coincidentally, on the
      northeastern coast of the United States of America. The epidemiology of the
      disease was unknown and no government action was taken following the initial
      outbreaks. This resulted in the disease spreading to other areas of Chile, as
      well as to Peru, Bolivia and Paraguay, reaching Venezuela and Colombia in the
      1950s, and Ecuador in 1961. The entire continent was affected in the 1960s when
      national FMD control programmes were initiated, with the exception of Guyana,
      Surinam, French Guiana and Patagonia. In the 1970s, steps were taken to implement
      a regional control and eradication strategy in view of the impact of production
      and trade on the persistence of the virus. The Plan Hemisferico de Erradicacion
      de la Fiebre Aftosa (PHEFA: Hemispheric FMD Eradication Plan), public- and
      private-sector policies, new diagnostic tools, the oil-adjuvanted FMD vaccine and
      regional strategies played a part in improving the epidemiological situation
      during the 1990s. A setback was encountered in 2000 and 2001, with outbreaks due
      to virus types A and 0 recorded in Argentina, Uruguay and Brazil.

PMID- 12523708
TI  - Control of foot and mouth disease: lessons from the experience of the outbreak in
      Great Britain in 2001.
AB  - An epidemic of foot and mouth disease occurred on an unprecedented scale in Great
      Britain in 2001. This was characterised by widespread dissemination of disease in
      sheep due to infection being present but unreported for at least three weeks
      before the first case was identified. As envisaged by the contingency plans,
      existing procedures dealt rapidly with disease in many parts of the country where
      outbreaks were reported. Elsewhere, the scale and speed of disease spread was so
      great that veterinary resources had to be supplemented on the operational front
      by a large influx of military and administrative support. At the time of writing
      (June 2002), the United Kingdom Government has already identified a number of key
      lessons, and will learn further from this experience and from the findings of
      inquiries, how a future outbreak of this unprecedented nature and extent could be
      handled. Lessons identified so far relate to the improvement of contingency
      plans, the wider impact on rural businesses and communities, reassessing the
      possible use of emergency vaccination, the availability of serological capacity,
      better animal identification and movement controls, carcass disposal,
      communications, data handling and management information. The authors present the
      initial lessons learned and which formed the basis of official submissions to the
      inquiries. Further lessons will be learned from the findings of those inquiries.

PMID- 12523709
TI  - Lessons from the foot and mouth disease outbreak in The Netherlands in 2001.
AB  - The Netherlands had recently developed a new strategy for the eradication of foot
      and mouth disease (FMD). When FMD was confirmed in Great Britain and France,
      recent imports of susceptible animals from these countries were traced and
      preventive measures were taken. On 21 March 2001, FMD was confirmed in The
      Netherlands. The disease was introduced by calves which became infected at a
      staging post in Mayenne, France, where infected sheep from Great Britain were
      present. A total of 26 farms were infected. Emergency vaccination of all
      susceptible animals was applied. Suppressive vaccination was chosen, implying
      that all vaccinated animals had to be slaughtered. Ring vaccination of all
      susceptible animals within 2 km of an infected herd was the standard procedure.
      However, in the 'Noord Veluwe', vaccination had to be applied to a larger area.
      The last affected farm was confirmed on 22 April 2001. Emergency vaccination
      contained the FMD infection rapidly. The last vaccinated animal was slaughtered
      on 25 May 2001. Many farmers were not convinced that the killing of their
      healthy, vaccinated animals was justified and tried to prevent the culling, but
      without success. Politicians and the public at large are now strongly opposed to
      the large-scale slaughter of vaccinated animals should a future outbreak of FMD
      occur. The Office International des Epizooties (OIE: World organisation for
      animal health) should incorporate control of vaccinated animals with non
      structural protein (NSP) tests in the chapter on FMD in the International Animal
      Health Code.

PMID- 12523710
TI  - Foot and mouth disease: lessons to be learned from the experience of France.
AB  - The appearance of foot and mouth disease (FMD) in the United Kingdom in late
      February 2001 took European veterinary services by surprise. Differences in the
      types of measures taken by European countries, and in the speed with which they
      were implemented, partly explain the different animal health situations observed.
      France, as a major importer of British sheep, is an interesting country to study.
      The measures taken there are described in detail, as is the history of the two
      cases registered on 13 and 23 March 2001. The crisis management procedure is also
      detailed. The majority of the decisions taken and protocols followed are part of
      the national intervention plan for FMD. However, experience has shown that it is
      also important to remain pragmatic and to be able to adapt to new developments
      during the implementation of the plan. While pre-emptive killing may indeed have
      reduced the number of outbreaks in France, the social impact of such measures
      also needs to be taken into account in the development of animal health policy.

PMID- 12523711
TI  - Control of foot and mouth disease: lessons from the experience of Ireland.
AB  - The authors outline the measures applied in Ireland to prevent the introduction
      of foot and mouth disease (FMD) from the United Kingdom, France and The
      Netherlands, to stamp out the disease in Ireland following confirmation of an
      outbreak on 22 March 2001 and to conduct serological surveillance in order to
      prove freedom from the disease. Successful control was the result of prompt
      action and extensive culling in the area around the infected premises. This was
      achieved by the State Veterinary Service operating with the assistance of the
      personnel and equipment resources of many Government departments, private
      industry and private veterinary practitioners, with the co-operation of the
      farming community and general public. In order to ensure effective use of these
      resources, good systems of communication and information technology are vital, as
      are the existence of detailed contingency plans and trained staff.

PMID- 12523712
TI  - Foot and mouth disease: the experience of South Africa.
AB  - Foot and mouth disease (FMD) is endemic in African buffalo (Syncerus caffer) in
      the Kruger National Park (KNP) and surrounding game parks in South Africa. The
      last outbreak of the disease in domestic stock outside the FMD control zone
      occurred in 1957. Due to the success in containing the disease, the country was
      accorded zone freedom from FMD without vaccination by the Office International
      des Epizooties (OIE: World organisation for animal health) in 1995. This status
      was lost in September 2000 when the first-ever recorded case of serotype O in
      South Africa was diagnosed in a piggery in KwaZulu-Natal after the illegal
      feeding of untreated swill. In November 2000, an outbreak of FMD caused by
      serotype South African Territories (SAT) 1 was diagnosed in a feedlot within the
      free zone of Mpumalanga Province. The SAT 1 outbreak was traced to cattle in the
      FMD control zone south of the KNP after the game-proof fence surrounding the KNP
      was severely damaged by floods. This enabled buffalo to come into direct contact
      with cattle outside the KNP. A further outbreak caused by SAT 2 was diagnosed
      within the FMD control zone in February 2001, also as a result of buffalo having
      escaped from the KNP. All these outbreaks were successfully contained, with the
      re-instatement of zone freedom from FMD without vaccination by the OIE in May
      2002. These outbreaks made it necessary to re-examine the methods of control and
      containment of FMD that have been practised for many years and which are in line
      with accepted international practices. The authors describe the rationale for the
      different control strategies that were followed, the need for a multidisciplinary
      approach to disease control, the interface between control and technological and
      diagnostic support and the lessons learned. Some suggestions for future control
      strategies are also offered.

PMID- 12523713
TI  - Global perspective for foot and mouth disease control.
AB  - The world distribution of foot and mouth disease (FMD) is almost a mirror image
      of the global economic structure. In general, industrialised countries are free
      while the disease is endemic in developing countries. In recent years, several
      incursions of FMD have been recorded in countries belonging to the Organization
      for Economic Co-operation and Development (OECD), all of which have been
      financially and socially costly to eliminate. At the same time, this single
      disease bars many developing countries from participation in formal trade, both
      regionally and internationally. However, recent studies have predicted an
      unprecedented high demand for animal protein, which can only be met through
      enhanced participation of developing countries in trade in livestock products.
      Accordingly, globalisation trends will exacerbate the exclusion of poor
      communities and countries from markets unless a long-term strategy is implemented
      to progressively build market opportunities for these countries, without placing
      the livestock of industrialised countries at undue risk from FMD and other major
      transboundary animal diseases. The authors submit that there is sufficient
      knowledge of FMD to make an international initiative for the progressive control
      of FMD a viable objective. Consequently, a four-stage pathway is proposed for
      developing a global FMD programme. The proposed strategy involves a build-up of
      the epidemiology and global status of FMD, including establishing an
      international early warning system, a risk-reduction phase to lower the incidence
      of FMD in the primary endemic areas and a control phase leading to the creation
      of zones of assured FMD-freedom. The authors also propose that an international
      FMD programme be co-ordinated, based on the experience of the Global Rinderpest
      Eradication Programme, the Hemispheric Plan for the eradication of FMD for the
      Americas, the South-East Asia Foot and Mouth Disease control and eradication
      campaign and the European Commission for the Control of FMD.

PMID- 12523714
TI  - Carcass disposal: lessons from Great Britain following the foot and mouth disease
      outbreaks of 2001.
AB  - The foot and mouth disease (FMD) outbreak that occurred in the United Kingdom in
      2001 was of an unprecedented scale and severity and presented a massive
      logistical challenge to Government. Over 6.5 million animals were slaughtered and
      disposed of, over 4 million as a direct result of disease and a further 2.5
      million on welfare grounds. On-farm burial and on-farm burning were the principal
      routes for disposal at the commencement of the outbreak. On-farm burial was
      limited by legislation to protect groundwater supplies and pyre burning came
      increasingly under attack from local communities concerned about health risks
      from smoke and emissions. Burning also painted a vivid but distressing picture of
      the war against disease. Increasingly, rendering capacity made an important
      contribution to disposal. The peak of the outbreak could only be managed by the
      development of a new disposal route--mass burial in engineered sites and by using
      licensed landfill where available. During the course of the outbreak, a disposal
      hierarchy was developed to reflect environmental and public health concerns,
      namely: rendering and incineration ranked first, licensed landfill next, followed
      by burning with mass burial or on-farm burial as the least preferred options.
      However, the campaign against the disease could not have been won without the
      tactical use of mass burial in addition to all the other available disposal
      routes. The authors describe the development and deployment of the disposal
      routes used in the 2001 outbreak.

PMID- 12523715
TI  - Carcass disposal: lessons from The Netherlands after the foot and mouth disease
      outbreak of 2001.
AB  - The main logistical problems of the foot and mouth disease (FMD) outbreak that
      occurred in the Netherlands in 2001 were a lack of culling and rendering
      capacity. Suppressive vaccination formed the basis for the solution to both
      problems and was primarily used to halt the possible spread of the virus. This
      allowed culls to take place on vaccinated farms when sufficient culling capacity
      eventually became available. In addition, the vaccinated cloven-hoofed animals
      could be removed alive and then killed in central culling places fourteen or more
      days after vaccination. Using slaughterhouses as central culling places meant
      that parts of carcasses could be deep-frozen, which solved the lack of rendering
      capacity. The deep-frozen carcass parts were destroyed later, when rendering
      capacity became available. To guarantee that all vaccinated, culled and
      temporarily deep-frozen cloven-hoofed animals were eventually destroyed, a
      balanced audit trail, partly based on kilogram records, was vital in this
      situation.

PMID- 12523716
TI  - Environmental impacts of the foot and mouth disease outbreak in Great Britain in
      2001: the use of risk analysis to manage the risks in the countryside.
AB  - Restrictions imposed for more than ten months throughout Great Britain in 2001 to
      control and eradicate foot and mouth disease (FMD) had a damaging effect on
      tourism and rural businesses. Risk assessment can play a valuable role in
      ensuring that the action taken is proportionate to the risk, and that countryside
      activities are allowed to resume when this can be done without compromising the
      objective of controlling and eradicating the disease. A risk assessment unit was
      established at the commencement of the epidemic to consider the risks posed by
      particular activities, to identify ways of managing those risks, and to make
      recommendations which could be used by policy makers when deciding what action to
      take. The assessments produced by the unit were published and the scientific
      rationale which supported policy and procedural changes was thereby exposed to
      public scrutiny and criticism. The author lists the activities subjected to
      veterinary risk assessments and describes how the process was used to consider
      public access to the countryside, leading to policy changes which within nine
      months resulted in the reopening of more than 96% of footpaths and bridleways
      without causing new outbreaks of FMD. A completed risk assessment is also
      included.

PMID- 12523717
TI  - Managing compensation for economic losses in areas surrounding foot and mouth
      disease outbreaks: the response of France.
AB  - This article describes the French scheme for providing compensation to stock
      farmers located in the prevention and surveillance zones in the vicinity of foot
      and mouth disease (FMD) outbreak sites and for economic losses suffered as a
      result of restrictions on animal and animal product movement. As early as 1991,
      the Groupements de Defense Sanitaire (GDS: Animal Health Groups--associations of
      stock farmers dealing with health issues, recognised under French law) set up a
      Compensation Fund that was put to use during the FMD episode of 2001. The Fund
      paid out FRF6,488,000 (Euro989,000) to stockbreeders in the five affected
      departments (French local administrative divisions). Based on the principle of a
      national mutual benefit society, the Compensation Fund is the first instance of a
      system of private compensation, outside of conventional insurance schemes, based
      on a convention between French stock farmers. With decentralised management and
      speed of implementation, the Compensation Fund has proved its worth. The Fund now
      needs to be adjusted on the basis of changes introduced in FMD control policy in
      France and possibly the European Union.

PMID- 12523718
TI  - A farming perspective on the 2001 foot and mouth disease epidemic in the United
      Kingdom.
AB  - The outbreak of foot and mouth disease (FMD) that occurred in the United Kingdom
      (UK) in 2001 was the single largest epidemic of FMD the world had ever
      experienced. This outbreak raises important issues about future FMD control
      strategies, including the use of vaccination. The outbreak has also stimulated a
      wider debate in the UK on the role and direction of agriculture. The author
      presents the views of the National Farmers' Union of England and Wales on the
      handling of the outbreak by the UK Government and summarises some of the key
      lessons to be learned from a farming perspective.

PMID- 12523720
TI  - Foot and mouth disease: the perspective of farmers in Ireland.
AB  - The first outbreak of foot and mouth disease (FMD) recorded in Ireland since 1941
      was successfully eliminated due to four main factors, as follows: --the
      willingness of the farmers in Cooley to sacrifice themselves in the national
      interest --decisive action was taken rapidly once the first outbreak was declared
      --geographical location of the Meigh and Proleek outbreaks which enabled the
      authorities to effectively seal off and regionalise the area, thus protecting
      exports from the rest of the country --national awareness and willingness at all
      levels, from Government to the general public, to take whatever action was
      necessary to keep FMD out of Ireland. The author recounts the story, from the
      perspective of a farmer, of the outbreak of FMD that occurred in Ireland in 2001,
      from the first confirmed case in Meigh, County Armagh, through Proleek and the
      cull, into dealing with the aftermath in terms of compensation payments, premia
      payments, the evolving human tragedy and lessons learned. Major policy issues
      must be addressed at both a national and European Union level to prevent
      outbreaks of FMD in Europe in the future. At a national level, the dual animal
      health status between Northern Ireland and Great Britain and between Northern
      Ireland and the Republic of Ireland must not be allowed to re-emerge. Some
      regulation loopholes allowed FMD to enter Ireland. The Government of Ireland
      handled the initial FMD crisis very well, with the co-operation of farmers and
      the public in general.

PMID- 12523719
TI  - The position of the Dutch Farmers' Union on lessons learned and future prevention
      and control of foot and mouth disease.
AB  - Foot and mouth disease (FMD) has devastated animal husbandry in The Netherlands
      frequently in the past and still constitutes a threat. The use of vaccination
      reduced the number of outbreaks in The Netherlands in the 20th Century. However,
      the desire of some member states of the European Community not to use vaccination
      led to a new strategy based on stamping-out of infected and contagious farms and
      to strict transportation regulations. In 2001, this proved very disruptive to the
      wider rural economy, such as the recreational and tourism sectors. The policy
      also caused severe animal welfare problems and psychological problems among
      farmers and their families. This raised questions about the wider, and not only
      veterinary or agricultural, implications of control strategies of foot and mouth
      disease virus (FMDV). The technology seems to be in place for a return to the use
      of protective vaccination against FMDV during an outbreak, provided the Office
      International des Epizooties (OIE: World organisation for animal health) and
      European Commission (EC) receive data that substantiate the reliability of
      differentiating tests such as the 3ABC enzyme-linked immunosorbent assay (ELISA)
      for use in individual animals. Research is in progress but may not be able to
      produce these data until 2003 or 2004. High potency vaccines should be used to
      elicit sufficient immunity within three to four days. During an FMD crisis,
      farmers should be assisted to find markets for products from areas affected by
      FMDV. The human dimension of any FMD outbreak must be dealt with sufficiently in
      any contingency plan.

PMID- 12523721
TI  - Animal welfare consequences in England and Wales of the 2001 epidemic of foot and
      mouth disease.
AB  - The ethical issues surrounding slaughter as a means of control of a disease
      epidemic are discussed and the use of this method as at least one component of
      the eradication of foot and mouth disease (FMD) is justified. The Royal Society
      for the Prevention of Cruelty to Animals received numerous complaints of
      suffering at slaughter during the FMD epidemic in the United Kingdom in 2001 but
      none led to prosecution because of lack of evidence. Movement restrictions
      imposed as part of the disease control strategy caused major welfare problems on
      farms which were unaffected by disease. These issues are detailed. Significant
      breaches of transport regulations appear to have occurred.

PMID- 12523722
TI  - The 2001 foot and mouth disease epidemic in the United Kingdom: animal welfare
      perspectives.
AB  - The management of the foot and mouth disease (FMD) epidemic which occurred in the
      United Kingdom (UK) in 2001 resulted in widespread animal welfare problems. These
      problems arose firstly because of the large numbers of animals slaughtered to
      bring the epidemic under control, which meant that the conditions under which
      animals were slaughtered and the manner in which this was carried out often
      breached regulations concerning welfare at slaughter. Secondly, the restrictions
      imposed on movements, especially animal movements, resulted in what appeared to
      be readily avoidable difficulties with livestock dying from, for example, food
      shortages and pregnant animals giving birth under unsuitable conditions. This
      brief review is based on the personal experiences of the authors as well as
      relevant observations and reports from a variety of sources.

PMID- 12523723
TI  - Future research on foot and mouth disease.
AB  - The recent outbreaks of foot and mouth disease (FMD) in Argentina, Europe, Japan,
      the Republic of Korea, South Africa and Uruguay have brought to world attention
      the devastating effects of the disease in a naive population and the social and
      economic costs of control and eradication. The fact that much still remains
      unknown about the natural history of FMD virus came as a surprise to some. This
      paper attempts to identify where research should be directed in order to be
      better prepared in the future.

PMID- 12523724
TI  - Sustainable development of water services industry.
AB  - The world population is expected to increase up to 8 billion by 2015. Most of the
      cities in the world are scattered around the fresh water resources. These cities
      and villages have their own interests and they constitute a power order.
      Therefore, we have been trying to harmonize these cities and villages in the
      usage of fresh water resources and the discharging of wastewater as well, by
      using an engineering means of water treatment. However, fresh water resources,
      which are essential to our lives, have a constant amount of circulation with a
      period of one week to ten days. The science and technology of the water
      environment should recognize the limit of fresh water resources for the
      sustainable development of society, because the water service industries are the
      essential infrastructure of the community. In order to implement an appropriate
      risk management it is necessary to identify the goal of environmental management
      considering the social, natural and economical conditions. The energy-dependent
      technologies should be reconsidered to consume less energy and undertake more
      resource conservation engineering. Water science and technology cannot supply all
      the answers, therefore more comprehensive water management systems should be
      developed by other sectors, such as the food production industry.

PMID- 12523725
TI  - OH radical monitoring technologies for AOP advanced oxidation process.
AB  - This study has been conducted to investigate OH radical monitoring technologies
      for the advanced oxidation process (AOP). OH radicals can be measured directly or
      indirectly through electron paramagnetic resonance (EPR), hydrogen peroxide
      method and probe compounds such as pCBA. Among the various AOPs, we focused on
      the application of EPR technique for *OH monitoring in the ultrasonic irradiation
      process. EPR method is a valuable tool and has a high sensitivity for radical
      measuring. Our study was performed with 20 kHz ultrasonic processor in 20 ml DMPO
      (1 mM) solution. The amount of DMPO-OH adduct with hyperfine constants aN = aH =
      1.49 mT and g-value 2.0054, coincided with those of the DMPO-OH adduct depends on
      the reaction time of the sonication. Also, we have found that at least, *OH was
      accumulated by 2 x 10(-10) M for 10 min sonication, when 60% of the initial
      amount was destroyed through *OH monitoring using a probe compound. With these
      results, we could assume that recombination of *OH to form hydrogen peroxide
      occurs at the interfacial region.

PMID- 12523726
TI  - Development of a simulator for ozone/UV reactor based on CFD analysis.
AB  - A new CFD (Computational Fluid Dynamics) simulator for an O3/UV reactor where
      ozone dissolved water flows under the irradiation of UV, has been developed by
      combining a fluid dynamics model with a complex radical reaction model. The
      radical reaction model used in this simulator was found to be reasonable, because
      the results obtained from the simulation of a completely stirred tank reactor
      (CSTR) system were in good agreement with the experimental results, e.g., the
      concentrations of total organic carbon (TOC), hydrogen peroxide and dissolved
      ozone obtained from a lab-scale CSTR. Furthermore, by using this CFD simulator,
      the distributions of substances such as hydroxyl radical (OH*) and hydrogen
      peroxide in the O3/UV reactor have been investigated. These distributions showed
      that this CFD simulator was considered to be reasonable. In addition, the
      simulation results suggested that conventional reactors were not optimized.

PMID- 12523727
TI  - Ozonation of Han River humic substances.
AB  - This study investigated the characteristics of extracted humic substances (HS)
      which are ubiquitous in river waters and affect the treatment of the water. HS
      were extracted from the Han River and the samples obtained were analyzed
      before/after oxidation with the following analytical methods: DOC, THMFP, UV-abs,
      chemical composition, molecular weight distribution, IR. Ozonation experiments
      were conducted in batch-type reactors. Ozone dose was 1 mg/L and contact time was
      varied from 0 to 20 minutes. The fraction of hydrophobic matter was 56.0% of
      total organic carbon in the Han River and the ratio of humic/fulvic acids was
      22.4/77.6, showing high fractions of aromatic and/or double carbon bond
      functional groups and high fractions of saturated aliphatic carbons. Oxygen
      fraction of Han HS was relatively high compared with other humic substances
      (Suwannee River humic and fulvic acids), which are consistent with the results of
      IR spectra. The IR spectra showed the increase in aliphatic groups by ozonation
      of the Han HS. Humic substances could not completely be oxidized to CO2, H2O
      etc., but were partly oxidized to low molecular weight matter (aliphatics,
      aldehydes, carboxylics, polysaccharides etc.), so low removal efficiencies in
      terms of DOC (31-35% with 5 minute contact) were observed. For UV254, 5 minute or
      shorter contact showed more than 80% removal efficiencies.

PMID- 12523728
TI  - Removal of bromate ion from water using TiO2 and alumina-loaded TiO2
      photocatalysts.
AB  - The effects of pH and the surface charge of photocatalyst on photocatalytic
      reduction of bromate ions in water were examined by using TiO2 and alumina-loaded
      TiO2 photocatalysts. The amount of adsorbed bromate ion on TiO2 and the reduction
      rate of bromate ion by the TiO2 photocatalyst increased with lowering pH. It was
      suggested that the bromate ion adsorbed predominantly on the positively charged
      surface sites of TiO2 at lower pH, which thus promotes the rate of reduction. The
      iso-electric point of the TiO2 photocatalyst was shifted to the higher pH region
      by loading alumina on the TiO2 surface, which resulted in the increase of the
      adsorbed amount of bromate on the photocatalyst and the reduction rate of bromate
      ion by the photocatalyst at neutral pH. It was concluded from these results that
      the photocatalytic reduction of bromate ion can be promoted by pH control of
      water or by controlling the surface charge of the photocatalyst by loading
      alumina without pH control of water.

PMID- 12523729
TI  - Inhibition effect of chlorine ion on hydroxyl radical generation in UV-H2O2
      process.
AB  - UV-H2O2 process is widely used as an advanced oxidation process (AOP) for the
      treatment of chlorine volatile organic compounds (CVOCs) such as dichloromethane
      (DCM) with strong oxidativity of hydroxyl radical generated from photolysis of
      H2O2. The result of DCM degradation rate at different initial concentrations in
      UV-H2O2 processes indicated the inhibition effect of produced chlorine ions on
      DCM oxidation processes, because the first-order degradation rate constant
      increased with lower initial concentrations. A spin trapping adduct of hydroxyl
      radical with 5,5-dimethyl-1-pyrroline-n-oxide (DMPO) was quantified by ESR
      spectrometer after UV irradiation in the presence of different amounts of
      chlorine ion, and as a result, the chlorine ion was found to act as a hydroxyl
      radical scavenger, which resulted in decreasing DCM degradation rate. An UV-H2O2
      reactor equipped with ion exchangers for removing chlorine ion achieved higher
      DCM degradation rate than that without ion exchangers.

PMID- 12523730
TI  - Nitrate removal rate in a continuous column denitrification reactor using
      hydrogen generated by electrolysis with carbon anodes and stainless cathodes.
AB  - An autotrophic continuous denitrification process, using hydrogen generated by
      electrolysis with activated carbon anodes, was experimentally demonstrated to be
      an effective nitrate removal process. Several fixed bed columns with
      polypropylene packing and honeycomb shaped activated carbon anodes and stainless
      rod cathodes were set in a thermostat chamber at 30 degrees C, and potassium
      nitrate enriched tap water as influent was supplied at various flow rates and
      electric currents. Although the anode is in the same column where microbial
      biomass grows, sufficient nitrate removal was observed. For example, almost
      complete removal of nitrate and nitrite was observed at a hydraulic retention
      time (HRT) as short as 1.8 h. A model assuming successive denitrification
      reactions and plug-flow process, nitrate reduction rate = k1 [NO3-] [H2], and
      nitrite reduction rate = k2 [NO2-] [H2](1.5) was proposed. Calculated results
      with k1 = 1.3 mmol(-1) h(-1) and k2 = 3.3 mmol(-1.5) x h(-1) agreed well with all
      the experimental results.

PMID- 12523731
TI  - Behavior of nuisance mussel, Limnoperna fortunei, in water supply facilities.
AB  - Limnoperna fortunei, a species of bivalve of foreign origin, was confirmed to
      exist in Japan for the first time in 1992. It was found in some facilities of
      Hanshin Water Supply Authority in 1994. Later, it was found to cause various
      problems such as clogging of sampling pipes. Following this finding, research was
      initiated to investigate the possibility of its causing major incidents of bio
      fouling such as total blockage of water passage by adhering to the raw water
      transmission pipe wall in massive numbers. As a result, it was found that
      Limnoperna fortunei was spawned in summer and grew up to 20 mm in size by the end
      of a one-year period when it began to die out and became detached immediately.
      Therefore, it was concluded that no deliberate efforts to remove them are
      required to avoid major problems.

PMID- 12523732
TI  - Biological treatment characteristics of benzene and toluene in a biofilter packed
      with cylindrical activated carbon.
AB  - The biodegradation of toluene and benzene in a biofilter using cylindrical
      activated carbon as the filler materials was studied. Three gas low rates, i.e.
      0.25, 0.50 and 0.75 m3/h, corresponding to empty bed gas residence of 75, 37.5
      and 25 s, respectively, and total organic load lower than 400 g/m3 x h were
      tested. The biofilter proved to be highly efficient in biodegradation of toluene
      and benzene, and toluene was more easily degraded than benzene. When each inlet
      load was lower than 150 g/m3 x h, removal rate increased with inlet load and
      reached a maximum, which was 150 and 120 g/m(-3) x h for toluene and benzene,
      respectively. For inlet load higher than the maximum removal capacity conditions,
      the removal rate decreased with inlet load. Carbon dioxide concentration profile
      through the biofilter revealed that the mass ratios of carbon dioxide produced to
      the toluene and benzene removed were 2.15 g(CO2)/g(toluene) and 1.67
      g(CO2)/g(benzene), which furthermore, confirmed the biodegradation performance in
      biofilter. The observation of biotic community demonstrated that the microbes
      consisted of bacillus, spore bacillus and fungi, of which the spore bacillus was
      dominant.

PMID- 12523733
TI  - Packed bed columns for high rate nitrogen and carbon removals.
AB  - Two packed bed column (PB) systems, namely anoxic-anoxic and anoxic-oxic were
      investigated for treatment of wastewater containing high concentrations of
      nitrogen (N) and COD. The anoxic-anoxic PB removal rates 6.70 kg N/m3 x d and
      26.02 kg COD/m3 x d, respectively. The responding removal rates of the anoxic
      oxic PB system were 7.41 kg N/m3 and 28.00 kg COD/m3 x d, respectively. The N and
      COD removal efficiencies of anoxic anoxic PB system were in the range of 99.2
      100% and 97.2-98.8%, respectively. The corresponding removal efficiencies of
      anoxic-oxic PB system were 97.5-100% and 98.6-99.4%, respectively. These findings
      showed that a PB system consisting of anoxic-oxic columns in series has a high
      capacity to remove nitrogenous and carbonaceous compounds even though the
      influent to the anoxic stage was oxygenated. Better system stability in terms of
      denitrification was, however, obtained with the anoxic-anoxic system.

PMID- 12523734
TI  - Modeling prediction of membrane bioreactor process with the concept of soluble
      microbial product.
AB  - The existence of soluble microbial products (SMP) produced by microbial cultures
      involved in biological wastewater treatment process has been widely investigated.
      This paper aims to establish an available mathematical model by incorporating the
      SMP concept into the Activated Sludge Model (ASM) No. 3. Prediction of sewage
      treatment performance in membrane bioreactor process under intermittent aerobic
      condition by model simulation was presented, and the results provided a more
      comprehensive image for this process. It was found that SMP could not be ignored
      and it contributed about 15% of total COD in the reactor under HRT = 12 hr and
      SRT = 10 days condition. The model also provided reasonable simulation results
      for nitrogen, biomass concentration, and other treatment behaviors. Furthermore,
      the treatment performance can be predicted under various operating conditions by
      this proposed model.

PMID- 12523735
TI  - Performance of coarse pore filtration activated sludge system.
AB  - A coarse pore filter can be applied inside the aeration tank to facilitate the
      separation of sludge from liquid instead of sedimentation. This filter has pores,
      which are irregular in shape, and the pore size is bigger than those of MF. The
      objectives of the study were to maintain as much as MLSS in the activated sludge
      process with coarse pore filter and to investigate the performance under high
      MLSS condition. Small-scale reactor results so far show good quality of effluent
      specially after starting the sludge bulking in the system in terms of SS, TOC,
      DOC and turbidity. The average carbon removal for 62 days operation of this
      system was about 94% (based on effluent DOC) and 87% (based on effluent TOC). The
      average sludge yield in this system is about 0.44 kg MLSS/kg TOC which is about
      0.24 kg MLSS/kg BOD. This amount is less than those of conventional activated
      sludge and trickling filter.

PMID- 12523736
TI  - Industrial wastewater minimization using water pinch analysis: a case study on an
      old textile plant.
AB  - Industrial wastewater minimization can be conducted using four main strategies:
      (i) reuse; (ii) regeneration-reuse; (iii) regeneration-recycling; and (iv)
      process changes. This study is concerned with (i) and (ii) to investigate the
      most suitable approach to wastewater minimization for an old textile industry
      plant. A systematic water networks design using water pinch analysis (WPA) was
      developed to minimize the water usage and wastewater generation for the textile
      plant. COD was chosen as the main parameter. An integrated design method has been
      applied, which brings the engineering insight using WPA that can determine the
      minimum flowrate of the water usage and then minimize the water consumption and
      wastewater generation as well. The overall result of this study shows that WPA
      has been effectively applied using both reuse and regeneration-reuse strategies
      for the old textile industry plant, and reduced the operating cost by 16% and 50%
      respectively.

PMID- 12523737
TI  - The nomographic design approach to recycled water reatment by the nitritation
      process.
AB  - The side-stream generated recycled water in the wastewater treatment plants is
      characterized as high in both nitrogen concentration and fluctuation of load.
      Thus, the design approach for recycle water management became an important part
      of the biological nutrient removal system design. The application of nitrogen
      removal from recycled water using the nitritation process has recently been
      increased due to economical reasons associated with an effective carbon
      allocation as well as the minimization of aeration cost. The concept of
      nitritation reactor design related to an inhibition of nitrite oxidizer has not
      been fully practiced in reality because of the limited field experiences. In this
      paper, a new approach has been proposed to determine reactor size and oxygen
      requirement in nitritation process design. The SRT-based design approach has been
      examined based on a series of laboratory experiments.

PMID- 12523738
TI  - Characterization of microbial community in nitrogen removal process of
      metallurgic wastewater by PCR-DGGE.
AB  - The metallurgic wastewater generated from the processes of recovering precious
      metals from industrial wastes contains high concentrations of nitrogen compounds
      such as ammonia and nitric acid and of salts such as sodium chloride and sodium
      sulfate. Biological nitrogen removal from this wastewater was attempted by a
      circulating bioreactor system equipped with an anoxic packed bed and an aerobic
      fluidized bed. The anoxic packed bed of this system was found to effectively
      remove nitrite and nitrate from the wastewater by denitrification at a removal
      ratio of 97%. As a result of denitrification activity tests at various NaCl
      concentrations, the sludge obtained from the anoxic packed bed exhibited
      accumulation of nitrite at 5.0 and 8.4% NaCl concentrations, suggesting that the
      reduction of nitrite is the key step in the denitrification pathway under
      hypersaline conditions. The microbial community analysis by denaturing gradient
      gel electrophoresis (DGGE) of PCR-amplified 16S ribosomal DNA (rDNA) fragments
      revealed that the community diversity varied in accordance with water
      temperature, nitrate-loading rate and ionic strength. When particular major DGGE
      bands were excised, reamplified and directly sequenced, the dominant species in
      the anoxic packed bed were affiliated with the beta and gamma subclasses of the
      class Proteobacteria such as Alcaligenes defragrans and Pseudomonas spp.,
      respectively.

PMID- 12523739
TI  - Denitrification of industrial wastewater with sulfur and limestone packed column.
AB  - An autotrophic denitrification system was developed for nitrate contaminated
      industrial wastewater whose C/N ratio was very low. The microbes containing
      Thiobacillus denitrificans as a dominant species were attached on the surface of
      granular elemental sulfur packed in a column. Elemental sulfur was used as an
      electron donor for autotrophic denitrification. The granules of limestone were
      mixed with the granular sulfur to moderate the decrease of alkalinity during
      autotrophic denitrification. The stoichiometry and basic kinetics of
      denitrification were studied in column runs. The effects of minerals such as
      phosphorus on treatment performance were clarified. The wastewater from steel
      production plants was treated by the present biofilm process. Low extent of
      nitrogen removal was caused by the lack of minerals.

PMID- 12523740
TI  - Community analysis of nitrifying bacteria in an advanced and compact Gappei
      Johkasou by FISH and PCR-DGGE.
AB  - Fluorescent in situ hybridization (FISH) method with 16S rRNA-targeted
      oligonucleotide probes was used for quantitative estimation of ammonia oxidizing
      bacteria (AOB) and nitrite oxidizing bacteria (NOB) in a Johkasou. Although the
      occupation ratios of AOB and NOB increased as nitrification progressed, about one
      month later, the occupation ratios decreased, despite showing good nitrification
      ability. Furthermore, even when urea was added to the feeding wastewater to raise
      the amount of T-N, the occupation ratios of both nitrifying bacteria remained
      constant. For further investigation, denaturing gradient gel electrophoresis
      (DGGE) was used to study the community structure of AOB in the Johkasou. As a
      result, DGGE band patterns and following sequence analysis revealed that the
      community structure of AOB was complicated and changed during this experiment. It
      was suggested that even if the occupation ratio of AOB to eubacteria was
      constant, the majorities of AOB were changed through temperature and load
      fluctuation. The combination of FISH and PCR-DGGE provides new information that
      was not available by conventional cultivation-based methods.

PMID- 12523741
TI  - Simultaneous removal of nitrogen and phosphorus with A2/O process using
      immobilized media.
AB  - It is necessary to introduce nitrogen and phosphorus removal processes in the
      existing wastewater treatment plants of Fukuoka City to improve the water quality
      of Hakata Bay. An A2/O (anaerobic-anoxic-oxic) process using immobilized media is
      proposed here, as a high-end technology to meet stricter discharge standards when
      faced with treatment space limitations. In order to investigate the applicability
      of the process, a pilot-scale study using municipal wastewater was conducted.
      Fluidized immobilization media were added to the aerobic reactor to maintain a
      high concentration of nitrifying bacteria and nitrification rate. Relationships
      between nutrient removal performance and varied operating conditions were
      examined. The results of the pilot plant test indicated that the process performs
      well for removal of nitrogen and phosphorus. Under the condition of HRT = 8 hr,
      it was possible to obtain an effluent water quality as follows: T-N<8.0 mg/L; T
      P<1.0 mg/L. It was observed that reaction time needed for a complete
      nitrification was shortened by the addition of immobilized media to the aerobic
      reactor, and longer reaction time would be needed for a completed phosphorus
      uptake process other than complete nitrification in an aerobic tank. Therefore,
      the phosphorus uptake rate, as well as nitrification process, should be
      considered as one of the important factors affecting the design parameters of an
      aerobic reactor.

PMID- 12523742
TI  - Reduction of sludge by ozone treatment and production of carbon source for
      denitrification.
AB  - The feasibility of ozone treatment of municipal sludge for sludge reduction and
      carbon source production has been investigated. Significant accumulation of
      solubilized organics and unsettlable micro-solids (UMS) was observed at
      relatively low ozone dosages while mineralization became dominant at higher
      dosages. Batch denitrification experiments showed that the solubilized organics
      and the UMS could be utilized as carbon sources for nitrogen removal. In terms of
      overall sludge reduction, 54% reduction of the total sludge mass could be
      achieved by ozone treatment at 0.2 g-O3/g-MLSS.

PMID- 12523743
TI  - Degradation of biotansformation products of nonylphenol ethoxylates by ozonation
      and UV/TiO2 treatment.
AB  - The degradation kinetics of biotransformation products of nonylphenol
      polyethoxylates (NPEOs), nonylphenol (NP), nonylphenol monoethoxylate (NP1EO) and
      nonylphenoxy carboxylic acid (NP1EC), by ozonation and UV/TiO2 (ultraviolet
      photocatalytic degradation in the presence of titanium dioxide suspension as a
      catalyst) were investigated using lab-scale reactors. The degradation rate of NP
      by UV/TiO2 was the highest among the tested NPEOs metabolites, while NP1EC showed
      the lowest degradation rate. In contrast, ozonation was especially effective for
      the breakdown of NP1EC. NP could be also degrade efficiently by ozonation,
      however, it was much less effective for NP1EO decomposition. Degradation of NP by
      both chemical oxidation processes followed first-order kinetics. The degradation
      curves of NP1EO and NP1EC could be approximately described by first-order
      kinetics also, although the degradation of NP1EC by ozonation seemed to follow a
      second-order kinetic.

PMID- 12523744
TI  - Decolorization of reactive bright red K2G dye: electrochemical process catalyzed
      by manganese mineral.
AB  - This paper presents the results of the decolorization of azo dye K2G by the
      electrochemical process catalyzed by manganese mineral. It is proved that the
      MnOOH(s), main component of the manganese mineral, can catalyze the
      electrochemical process and enhance the decolorization efficiency. X-ray powder
      diffraction spectrum shows that the content of MnOOH(s) has not been changed at
      the end of the reaction. The effects of initial pH value, current density,
      concentration of electrolyte on the decolorization efficiency of the dye were
      investigated in detail. The initial pH effect on the decolorization efficiency of
      K2G dye is found not to be significant. The optimum current density is 0.26
      A/dm2. In addition, a proposed catalyzing mechanism of manganese mineral is
      discussed in this paper.

PMID- 12523745
TI  - Photocatalytic degradation of explosives contaminated water.
AB  - This study was undertaken to examine the degradation of TNT, RDX and HMX in a
      circular photocatalytic reactor with TiO2 as a photocatalyst. We examined the
      impact of parameters such as the initial concentration, initial pH of solution on
      rates of photocatalized transformation, and the mineralization. The results
      showed that photocatalysis is an effective process for the degradation of TNT,
      RDX and HMX. They could be comoletely degraded in 150 min with 1.0 g/L TiO2 at pH
      7. An increase in the photocatalytic degradation of HMX was noticed with
      decreasing initial HMX. The rates of RDX and HMX degradation were greater in
      neutral pH than in acidic and alkaline conditions. In case of TNT degradation,
      the rate of degradation was the fastest at pH 11. Approximately 82% TOC decrease
      in the TNT degradation was achieved after 150 min, whereas TOC decrease in RDX
      and HMX was 24% and 59%, respectively. Nitrate, nitrite, and ammonium ions were
      detected as the nitrogen byproducts from the photocatalysis, and more than 50% of
      the total nitrogen was recovered as nitrate ion in every explosives.

PMID- 12523746
TI  - Phosphate removal and recovery by a novel electrolytic process.
AB  - The possibility of removing and recovering phosphate from wastewater by a novel
      electrolytic process was investigated experimentally. In the process, ion
      electrodes are immersed in synthetic wastewater and direct current (DC) is
      applied to coagulate phosphate on the surface of the anode. Experimental results
      demonstrated that at electric current densities ranged from 0.001 to 0.1 mA/cm2,
      phosphate was removed and recovered as phosphate-rich aggregates formed on the
      anode surface. Decreases in phosphate concentration at bulk liquid were in fairly
      good agreement with the amounts of phosphate in the aggregates. Moreover, the
      removal rate of phosphate was increased with increasing electric current. In
      addition, as heavy metal anions such as Cu2+ deposit on the counter electrode
      (cathode), it was thought that relatively pure phosphate could be obtained by the
      present process.

PMID- 12523747
TI  - Anaerobic acidification of a synthetic wastewater in batch reactors at 55 degrees
      C.
AB  - Experiments were conducted to study the acidogenesis of a dairy wastewater in
      batch reactors at pH 5.5 and 55 degrees C. There was a biased fermentation
      sequence for carbohydrate and protein, and the protein fermentation was delayed
      by carbohydrate. The production of hydrogen was exclusively from the fermentation
      of carbohydrate. Acetate and butyrate concentrations both increased rapidly at
      the beginning and peaked at some points, then declined in the reactors fed with 8
      g-COD (chemical oxygen demand)/l, or higher concentrations. Butanol and propanol
      fractions increased with the substrate concentration. The metabolism shifted from
      the volatile fatty acid-producing pathways to the alcohol-producing pathways when
      the substrate concentration increased beyond 8 g-COD/l. The acidogenic biomass
      yield was in the range 0.19-0.25 mg-VSS/mg-COD.

PMID- 12523748
TI  - Design parameters of high rate algal ponds using filamentous algae matrix for
      treating rural stream water.
AB  - High rate algal ponds (HRAP) with a filamentous algae matrix (FAM) as the
      predominant species, were operated to evaluate the characteristics of FAM and the
      basic design parameters for treating polluted rural stream water. The porous and
      gelatinous FAM was formed like a sponge, which functions to prevent excessive
      loss of the algae in the effluent and can easily be retrieved from the ponds. The
      organic fraction of harvested FAM was about 88%, which is suitable for use as
      fertilizer. The HRAP system using FAM was found to be an effective nutrient
      removal process not requiring any artificial carbon sources for nitrification. At
      HRT 4 days, the T-N and T-P removal efficiencies were 85.9% and 65.8%,
      respectively. When the pH and water temperature were maintained above 9 and 15
      degrees C, HRT required for achieving a 70% T-N removal efficiency could be
      reduced by about 3 days. The oxygen production rate by FAM was calculated as 1.45
      mgO2/L/m2. The design surface area of HRAP needed per rural inhabitant was about
      2.72 m2.

PMID- 12523749
TI  - Oilfield produced water treatment with surface-modified fiber ball media
      filtration.
AB  - In order to explore the PET fiber's potential as a filter medium to treat the
      water produced from oil production, modification technology was adopted to modify
      the fiber surface. After modification, the PET fiber surface was grafted by the 
      COOH, =NH and -OH groups. Therefore, the property of the modified fiber changed
      from oleophilic to hydrophilic, which makes the fiber easy to backwash. Water
      produced from atypical oil field in the north of China was treated on site with
      filter filled with this new fiber medium. The results are compared with the
      results from a filter filled with currently popular walnut medium, where the
      experiment conditions are the same as that of the fiber filter. When the velocity
      is lower than 15 m/h, the effluent from fiber filter can control the oil
      concentration < 2.4 mg/l, SS < 2.0 mg/l, and D50 < 2 microm, which meets the
      requirements for waterflood (water injection) into the ground. But the walnut
      medium filter can only control the oil concentration < 5 mg/l, TSS < 2.0 mg/l,
      and failed to control the d50 < 2 microm, which is the crucial deficiency of the
      walnut medium. The fiber medium still shows a great ability to control particles
      even with higher filtration velocity and worse influent. With a filtration
      velocity of 20 m/h and 36.4 microm d50 of influent, the d50 of the fiber filter
      effluent is 3.302 microm, but that of walnut filter is 10.74 microm. The reason
      for this is due to the compressibiliy of the fiber medium while the walnut median
      is incompressible. Recommendations for future studies on pilot-scale experiments
      to improve backwash and to determine operational parameters are presented.

PMID- 12523750
TI  - A preliminary study on electrically enhanced crossflow microfiltration of CMP
      (chemical-mechanical polishing) wastewater.
AB  - Chemical-mechanical polishing (CMP) is currently one of the main technologies
      used by wafer plants in the semiconductor industry. Normally, a large amount of
      de-ionized water should be used to wash out the abrasives adhered to the surface
      of wafers during the grinding process. Therefore, CMP wastewater not only has a
      great quantity but also contains very small size of suspended solids. Generally,
      these suspended solids would not settle. This phenomenon results in a low
      visibility of CMP wastewater. To solve this problem, a study on electrically
      enhanced crossflow microfiltration of CMP wastewater was conducted. Normally, the
      membrane of traditional dead-end filtration is easily blocked by the filter cake
      resulting in a small flux of filtrate. Therefore, the form of crossflow
      filtration (CFF) is used to reduce the blocking of the membrane. Furthermore, if
      CFF is accompanied by an external electric field, the negatively charged
      suspended solids in wastewater would move toward the positive electrode.
      Meanwhile, the flux of filtrate would increase. In this investigation, CMP
      wastewater was obtained from a wafer plant and characterized by various standard
      methods. Before testing, the CMP wastewater was pre-filtered using a 1.2 microm
      pore size filter. Then it was operated by a crossflow microfiltration (0.1 microm
      pore size) system under an appropriate crossflow velocity, filtration pressure,
      and electric potential. The filtrate was also characterized by various standard
      methods. Experimental results show that the filtrate has a turbidity of zero
      value. Thus, the filtrate could be reused for other purposes. However, the
      suspended solids of the CMP wastewater would be concentrated by this method.
      Therefore, the recovery of the suspended solids would be worth considering.

PMID- 12523751
TI  - Treatment of agricultural wastewater and reuse.
AB  - The use of membrane separation technology, such as ultrafiltration (UF) and
      subsequent reverse osmosis (RO), for purifying different types of low
      contaminated wash water of carrots (COD = 1,314 mg/l) and wash water of different
      kinds of vegetables (COD = 2,280 mg/l) was investigated on a pilot scale to
      determine its suitability for reuse in the process. In both membrane processes,
      UF and RO, the permeate flux first decreased with increasing fouling (deposition
      of organic and inorganic substances on the membrane surface and in its pores).
      After that the membrane permeability (permeate flux) and selectivity (rejection
      of COD) remained constant on a stable level in spite of a concentration with a
      volumetric concentration factor of up to 39. The tests showed that water can be
      obtained with a quality complying with the German regulations by applying a
      process combination of UF and RO. It was found that the membranes gave a 5-log
      reduction for total bacteria, and no coliform bacteria were present in the
      permeate after RO. Using UF and RO, part of the wastewater can be recovered for
      reuse in the process if drinking water is used for the last step of vegetable
      washing.

PMID- 12523752
TI  - Removal of suspended substances by coagulation and foam separation from municipal
      wastewater.
AB  - A new method for solid-liquid separation for wastewater incorporating simple
      operation and shortened treatment time is necessary for improvement of sewage
      systems. In this study, removal of suspended solids from municipal wastewater by
      coagulation and foam separation using coagulant and milk casein was examined. By
      adding casein before the foam separation process, the removal of suspended
      substances was dramatically improved. The optimum condition for treating sewage
      was 20 mg-Fe/L of FeCl3, 3 mg/L of casein, and pH 5.5, which resulted in a
      removal rates of over 98% for turbidity and SS. A removal of 96-98% was also
      possible for phosphate and anionic surfactant. When PAC was used, the floc was
      also efficiently recovered in foam by the addition of casein. It became clear
      that coagulation and foam separation using casein as the collector is an
      effective method for removing suspended solids in municipal wastewater in a short
      time (within 10 min).

PMID- 12523753
TI  - Isolation and examination of copper removing bacteria from activated sludge
      culture.
AB  - Experiments were carried out to isolate metal removing bacteria from activated
      sludge culture and test the metal removal capability of isolated bacteria. Two
      concentrations of copper solution (CuCl2) used to select the copper-tolerance
      level of each isolate were 0.05 mM and 2.5 mM. Experimental data showed that
      isolates could be obtained by using non-selective medium (NSM) in the presence of
      copper. The isolates were displayed on agar plates with diverse colonial
      morphological characteristics. A maximum uptake of 81 mg/g dry cell mass was
      observed at an initial copper concentration of 50 mg/l. The minimum uptake was 9
      mg/g dry cell mass. Copper uptake efficiency by isolates from NSM with 0.5 mM
      CuCl2 was significantly different with those from NSM with 2.5 mM CuCl2.

PMID- 12523754
TI  - Removal of pyrene by different microalgal species.
AB  - The efficiency of seven microalgal species, namely, Chlamydomonas sp., Chlorella
      miniata, Chlorella vulgaris, Scenedesmus platydiscus, Scenedesmus quadricauda,
      Selenastrum capricornutum, and Synechosystis sp. to remove pyrene from solution
      varied from species to species. According to the 6-hour, 12-hour, and 7-day
      exposure data, S. capricornutum was the most efficient species in the removal of
      pyrene, followed by S. platydiscus (a local isolate), and the least effective
      species was C. vulgaris. For all species, the removal was very rapid in the first
      3 to 6 hours of treatment, and no significant difference was found between live
      and dead cells of C. miniata, C. vulgaris and S. capricornutum, indicating that
      the initial removal was due to passive physico-chemical biosorption. More than
      65% of the pyrene adsorbed was bound on cell wall materials of S. capricornutum,
      suggesting the major binding sites were on cell walls. The pyrene removal was
      also dependent on the concentration of algal biomass used, the more the biomass
      the higher the removal percentages. In addition to biosorption, pyrene was
      accumulated and transformed inside live cells. In 7-day S. capricornutum culture,
      pyrene was not detected in either culture medium or algal pellets, and pyrene
      might have been completely transformed by this species. The degree of
      bioaccumulation and biotransformation was species specific.

PMID- 12523755
TI  - A mathematical model for the flotation of waste activated sludge.
AB  - A mathematical model that describes a batch flotation process is presented. The
      model employed a similar method to the hindered settling of flocculated material.
      This idea is based on our experimental results that the time growth curves of
      separated liquor zone showed a similar character to the settling curve of
      flocculated material, when the vertical axis reversed. In this model, it is also
      assumed that the gas phase and solid phase have the same movement, that is
      microbubbles and solid sludge particles joined to form aggregated floc. By
      comparing the numerical prediction with experimental data, the usefulness of the
      model is confirmed and some examples of flotation simulation are demonstrated.

PMID- 12523757
TI  - Long-term experimental study of the aquatic plant system for polluted river
      water.
AB  - Water purification using artificial wetlands and aquatic macrophyte is attracting
      attention as a purification technology that can create rich ecosystems while
      imposing a minimal load on the environment. Because an aquatic plant system
      requires a large surface area, design specifications and maintenance methods that
      can obtain the optimum purification effect per unit surface area must be
      established. Large experimental facilities have been constructed beside a
      polluted river flowing into Lake Kasumigaura and have been used for a three-year
      experiment using several kinds of aquatic plants. This report summarizes the
      characteristics and the design load of the aquatic plant system based on this
      study and results from other aquatic plant facilities.

PMID- 12523756
TI  - The impact of sea water flushing on biological nitrification-denitrification
      activated sludge sewage treatment process.
AB  - The process performance of the two largest activated sludge processes in Hong
      Kong, the Sha Tin and the Tai Po Sewage Treatment Works (STW), deteriorated in
      the initial period after the introduction of seawater flushing in 1995 and 1996,
      respectively. High effluent ammonia nitrogen (NH4-N) and total suspended solids
      (TSS) in excess of the discharge standards resulted from incomplete nitrification
      and changes in floc characteristics. A desktop study on the inhibitory effects of
      salinity, particularly on nitrification, was subsequently conducted using the Tai
      Po STW operating data. To assist the upgrade of the Sha Tin STW a five-month
      extensive bench-scale investigation on a simple but flexible modified Ludzack
      Ettinger configuration with bio-selector was conducted to quantify the inhibitory
      effects due to the saline concentration. The Sha Tin STW upgrade consists of
      restoration of its original design capacity (conventional process) of 205,000
      m3/day from its currently much reduced capacity as a Bardenpho process. Only the
      volume of the existing biological process and clarifier is to be utilized. The
      saline concentration ranges from 3,500 up to 6,500 mg Cl-/L, both daily and
      seasonally. High and greatly fluctuating saline concentrations have been known to
      inhibit nitrification. Design consideration should also be given to the peak
      daily and seasonal TKN loading of up to three times the average. Although the
      nitrifiers maximum specific growth rate was significantly reduced to a low 0.25
      day(-1), the inhibition was considered to be tolerable with effluent NH4-N and
      NO3-N consistently at < 1 and < 6 mg/L. The bio-selector was demonstrated to be
      efficient in control of sludge foaming and bulking with SVI consistently < or =
      125 mL/g. Results from the IAWO Model No. 1 and the hydraulic model of the
      secondary clarifiers allowed overall process capacity maximization. With an
      anoxic mass fraction of 25-30%, operating sludge age of 9-14 days and SVI < or =
      125 mL/g, both the design requirements and the effluent discharge standards could
      be met. Without these investigations, an unnecessarily large reaction basin and
      secondary clarifier volume, and hence capital investment, would have resulted.

PMID- 12523758
TI  - Simultaneous removal of cadmium and turbidity in contaminated soil-washing water
      by DAF and electroflotation.
AB  - The removal of cadmium and turbidity from contaminated soil-washing water was
      studied by dissolved air flotation (DAF) and electroflotation at laboratory scale
      by using sodium lauryl sulfate (SLS) as an anionic surfactant, and calcium
      hydroxide (Ca(OH)2) as a coagulant. Using DAF, and in the presence of SLS or
      Ca(OH)2, the maximum recovery rate of cadmium obtained at a stoichiometric
      cadmium to collector and coagulant ratio of 1:4.5 was 51.1% and 80.8%, while the
      removal rate of turbidity was 18.4% and 19.2%. However, satisfactory cadmium and
      turbidity removal was not obtained by DAF. Much more significant removal of
      cadmium (100%, not detected in the residual) and turbidity (95.7%) was obtained
      by electroflotation using an aluminium metal plate as electrode, which generated
      hydroxide and aluminum ion. As a consequence, electroflotation is considered an
      effective method to separate cadmium and turbidity from contaminated soil-washing
      water. The electroflotation process may have practical applications for the
      removal of other hazardous metals from contaminated soil-washing water.

PMID- 12523759
TI  - The influence of artificial cutoff on a monitoring system and the water quality
      of the Keelung River.
AB  - The purpose of this study was to design a water quality monitoring network for
      the Keelung River in order to evaluate the effects of artificial cutoff across
      two bend channels. A steady-state water quality model was used to simulate the
      BOD and DO curves. The Kriging theory was applied to select the optimal locations
      for a water quality monitoring network. The sampling frequency was determined by
      the coefficients of variation of water quality and by considering the
      significance level and confidence interval. After calibration and verification of
      the water quality model, the model was applied and the simulation results
      indicated that the values of DO in the new channel would be higher than those of
      the old channel reaches. The critical point of the oxygen sag curve would shift
      to the mouth of river under O75 low-flow conditions, and the BOD values in the
      new channel would also slightly increase. The results further indicated that more
      monitoring stations would be needed in the downstream reaches.

PMID- 12523760
TI  - Degradation of microcystin by biofilm in practical treatment facility.
AB  - Potential for degradation of microcystin by biofilm was examined by some batch
      experiments using biofilm scraped from practical biological treatment facility
      combined with conventional treatment processes. The viable cells of Microcystis
      viridis, which produced microcystin LR, RR and YR were degraded at 6 to 10 days
      by the addition of biofilm. Biofilm collected in summer season had especially
      higher potential for degradation of Microcystis with complete degradation at 6
      days. In all seasons, Monas spp. grew remarkably, accompanied with the higher
      decrease of the viable cells of Microcystis and the micro-animals were considered
      as a main predator for Microcystis cells. Intracellular microcystin LR, RR, YR
      were degraded simultaneously with high reduction of Microcystis cells. Dissolved
      microcystin LR of 1,000 microg l(-1) was effectively degraded by indigenous
      aquatic bacteria on biofilm during 5 days, the degradability became higher with
      the increase in the concentration of microcystin LR. From the results of our
      research, it was clarified that the aggregated microorganisms consisting of
      biofilm had high potential for degradation of intracellular and dissolved
      microcystin.

PMID- 12523761
TI  - China's water environment at the beginning of the 21st century: challenges and
      countermeasures.
AB  - Water environment crisis is a common challenge throughout the world, and the
      situation is becoming worse. This paper analyzes the development trend of water
      environment worldwide, and then evaluates the status of China's water environment
      and the progress in the work of protection of the water environment. According to
      the future development of economy and society in China, the paper discusses the
      severe challenges in water environment that China faces at the beginning of the
      21st century and proposes related countermeasures.

PMID- 12523762
TI  - Bio-affecting mercury detection using mercury resistance gene module fused with
      bioluminescence reporter genes.
AB  - Bioluminescence sensor systems were developed for monitoring environmental
      mercury contamination. The biological mercury measurement sensor systems were
      constructed by DNA recombination technique. A bacterial mercury-resistant operon
      (meroperon) from Pseudomonas sp. K-6y4 and a bacterial bioluminescence operon
      (lux operon) from an ocean bacterium Vibrio fischeri were fused in avector
      plasmid. The resulting recombinant plasmids were cloned in Escherichia coli
      cells. The bioluminescence sensor systems responded to mercury chloride of 0.1 nM
      to 100 nM. The mercury bioluminescence sensor developed in this study can be used
      for monitoring of the bio-affecting mercury instead of total mercury that is
      measured by conventional analytical equipment. The fundamental feature of the
      bioluminescence sensor system is attractive for use as a monitoring system for
      bio-affecting environmental mercury contamination.

PMID- 12523763
TI  - Characterization of an algae-lytic substance secreted by Bacillus cereus, an
      indigenous bacterial isolate from Lake Kasumigaura.
AB  - In order to develop a practical biological strategy for water bloom-control in
      Lake Kasumigaura, indigenous algae-lytic bacteria targeting Microcystis spp. (the
      dominant cyanobacteria), was first carried out. Some basic lytic characteristics
      of the isolates concerning the biological and physico-chemical factors in actual
      water environments were then investigated. Fifteen algae-lytic bacteria were
      successfully isolated using the double layer method. The isolate showing the
      highest lytic activity was identified as Bacillus cereus based on the 16SrRNA
      sequence. Extracellular products of B. cereus were found to be responsible for
      algae-lytic activity. Algae-lytic assay tests using bacterial supernatants pre
      treated under several conditions indicated that the majority of the effective
      algae-lytic substances were either hydrophilis or hydrophobics with a carbon
      number less than 18, and with molecular weight less than 2000 Da. The algae-lytic
      activity of the bacterial supernatant was found to be enhanced under alkaline
      conditions, but it was lost under acidic conditions. This pH specific
      characteristic is advantageous for application in water bloom environments where
      the pH is usually in the alkaline region.

PMID- 12523764
TI  - Environmental risk evaluation for anionic surfactants based on the
      characteristics of appearance of high concentration in rivers.
AB  - Environmental risk evaluation for anionic surfactants based on the
      characteristics of the appearance of a high concentration was developed together
      with statistical analysis of MBAS data in rivers of Hyogo Pref., western Japan.
      Annual average MBAS at different monitoring points generally decreased during
      past 10 years and their geometric mean reduced by 70%. This rate of decrease
      agreed well with that of estimated environmental loads of anionic surfactants in
      the study area. The proportions of monitoring point with high risk (risk ratio
      over 1.0) to fish increased in the order of the weakness of toxicity in both 1989
      and 1998. Their proportions were 2% for acute toxicity, 17% for chronic toxicity
      and 66% for avoidance response in 1989, which surpassed the proportion evaluated
      using average concentration in all cases. The proportions for whole toxicities
      decreased in 1998, however, the proportion for avoidance response kept
      considerably high level (42%). These results indicated the usefulness of
      environmental risk evaluation for surfactants based on the characteristics of
      appearance of high concentration, and also suggested the need for field
      investigation for fish avoidance response.

PMID- 12523765
TI  - Field survey on water supply, sanitation and associated health impacts in urban
      poor communities--a case from Mumbai City, India.
AB  - A field survey was conducted on four slum, squatter and pavement dweller
      communities of Mumbai City, India with a total sample size of 1,070 households.
      Study revealed extremely low water consumption pattern averaging merely 30 l/c x
      d, no sewerage and safe excreta disposal facilities manifested by high occurrence
      of water-borne diseases. The annual diarrhoeal, typhoid and malaria cases were
      estimated to 614, 68 and 126 per thousand populations respectively. At point
      prevalence scale, at least 30% of all morbidity can be accounted for by water
      related infections. In addition to the impacts of neighborhood water pollution
      and sanitation, such diseases were also found positively correlated with low
      water consumption and poverty related factors as, poor housing and family income.
      Analysis of variance also revealed intra-poor gradient both in living standards
      and health conditions on which the pavement dwellers were observed to be the
      greatest sufferers of all.

PMID- 12523766
TI  - Progress and data gaps in quantitative microbial risk assessment.
AB  - Quantitative microbial risk assessment (QMRA) has emerged as a useful tool to
      develop criteria for human exposures to pathogens. There is opportunity to extend
      the usefulness of this tool in water and other applications if new fundamental
      information can be obtained to complement existing data. Such information
      includes effects of strain and host differences, population level disease
      dynamics, and ability of animal data to serve as a predictor of human potency.
      This paper reviews the development of QMRA and outlines the nature of additional
      data that would be useful for its development.

PMID- 12523767
TI  - Fate of coliphage in waste water treatment process and detection of phages
      carrying the Shiga toxin type 2 gene.
AB  - Abundances of phages specific to Escherichia coli in the wastewater treatment
      process were analyzed. Relatively abundant coliphages were detected in sewage
      influent. Phages in the influent were found both suspended in liquid phase and
      attached on the solid particles. Phage concentration was not reduced in the
      settling tank without chemical agglutination. Anaerobic followed by aerobic
      treatment of the sewage reduced concentration of suspended phages. Almost no
      phage was detected as a suspended form in the aerobic tank. Most of the phages
      were detected as attaching form and were excluded by aggregation with sludge.
      Using an experimental approach based on the detection of Shiga toxin 2 (Stx 2)
      gene by a phage enrichment culture followed by nested PCR, bacteriophages
      carrying Stx 2 gene were detected in the influent, settling tank, and anaerobic
      tank. It was revealed that the presence of phages carrying Stx 2 gene is common
      in sewage and these phages are effectively eliminated through sewage treatment
      process.

PMID- 12523768
TI  - Sunlight inactivation of human enteric viruses and fecal bacteria.
AB  - Three human enteric viruses (poliovirus, echovirus, coxsackievirus) suspended in
      seawater or buffer were stable for 6 hr in the absence of sunlight but were
      inactivated at the same rate in the presence of sunlight. Under summer sunlight
      conditions, at least 3 logs of these viruses were inactivated by one-hit kinetics
      while under winter sunlight conditions only 1 log of these viruses was
      inactivated by two-hit kinetics. Under these same conditions, 6 logs of E. coli
      were inactivated within 1 hr by one-hit kinetics under summer and winter
      conditions. In comparison, E. faecalis was inactivated by two-hit kinetics and
      only 2.5 logs of inactivation were observed after 4 hr of exposure to winter
      sunlight. Since human enteric viruses are considerably more resistant to sunlight
      inactivation than E. coli and moderately more resistant than E. faecalis, marine
      recreational water quality standards should be based on concentrations of
      enterococci and not on coliform bacteria. Since the mechanism and rate of
      inactivation of coliphage and human enteric viruses are similar, coliphages
      appear to be the best indicator for the presence of human enteric viruses in
      recreational waters, especially coastal waters where abundant sunshine is
      available.

PMID- 12523769
TI  - Continuous monitoring for Cryptosporidium--a novel approach to public health
      protection.
AB  - Regulations requiring water utilities in England and Wales to carry out
      continuous monitoring for Cryptosporidium in treated water were introduced in
      June 1999. The rationale of the Regulations and the technical basis for the
      sampling and analysis are reviewed. The results of the first nine months of
      monitoring are summarised and compared with other equivalent data sets. The
      impact of the Regulations on water utilities operational practices and the
      implications for public health protection are discussed.

PMID- 12523770
TI  - Removal of indigenous coliphages and fecal coliforms by a novel sewage treatment
      system consisting of UASB and DHS units.
AB  - A novel sewage treatment system, which consists of an upflow anaerobic sludge
      blanket (UASB) pre-treatment unit and the following downflow hanging sponge (DHS)
      unit for polishing up the UASB effluent, was developed as a cost-effective and
      easy-maintenance sewage treatment system for developing countries. A long-term
      experiment with actual sewage was conducted in order to evaluate its treatment
      efficiency of organic substances, nutrients, and pathogen indicator
      microorganisms such as total coliphages, F+-specific RNA coliphages (RNA
      coliphages), and fecal coliforms. The main objective of this paper is to
      investigate the removal efficiency of those indicator microorganisms by the UASB
      DHS combined system. The results obtained from the continuous flow experiment
      indicated a fairly promising removal of the indicator microorganisms, i.e., the
      log10 reductions of total coliphages, RNA coliphages, and fecal coliforms (based
      on sewage and DHS effluent) achieved were 2.01 log, 2.02 log, and 2.57 log,
      respectively. The UASB-DHS combined system was superior to the conventional
      activated sludge process in the reduction of fecal coliforms, but in the
      reductions of total and RNA coliphages, the system showed somewhat less removal
      efficiency. The vertical reducing patterns of the indicator microorganisms along
      the DHS reactor were also discussed.

PMID- 12523771
TI  - Disinfection kinetics of Legionella pneumophila by ultraviolet irradiation.
AB  - Disinfection kinetics of Legionella pneumophila by ultraviolet irradiation was
      investigated. The change in viable cell concentration with exposure time could be
      divided into three steps: lag step in which little change in viable cell
      concentration was observed, fast disinfection step and slow disinfection step.
      The slow disinfection step was not observed at the initial cell concentrations
      below about 10(6) cfu/mL. The disinfection kinetics were well described with two
      parameters; lag time and disinfection rate constant of the fast disinfection
      step. The effects of UV intensity, temperature and initial cell concentration in
      the kinetic parameters were investigated. With increasing initial cell
      concentration, the lag time decreased and the disinfection rate constant
      increased. The effects of initial cell concentration on the kinetic parameters
      were considered to be attributed to the decrease in the effective UV irradiation
      intensity due to the partial shield of UV light by the disinfected cells. The
      empirical correlations were presented for predicting the lag time and
      disinfection rate constant. Furthermore, UV disinfection of L. pneuophila in a
      model hot-tub connected with external irradiation chamber was also discussed.

PMID- 12523772
TI  - Assessment of risk of infection due to Cryptosporidium parvum in drinking water.
AB  - The risk of infection of Cryptosporidium via drinking water was assessed using
      Monte Carlo simulation with the field survey data of the Sagami River watershed.
      The levels of Cryptosporidium in this river were found to follow the lognormal
      distribution. From the counted data, the median level of the Miyayama sampling
      point was estimated to be 5.7 oocysts per 100L. To calculate the annual risk of
      infection due to Cryptosporidium in drinking water, the Cryptosporidium level of
      Miyayama sampling point was used as the water source of the waterworks. The 95%
      percentile of the annual risk of infection was found to be 10(-2.60). If the
      daily risk was eliminated when the level of Cryptosporidium in treated water
      exceeded 1 oocyst per 20L, the 95% percentile of the annual risk was reduced by
      about 1 log. To reduce the 95% value of the annual risk lower than 10(-4), the
      risk of days with levels of Cryptosporidium in treated water exceeding 1 oocyst
      per 80L should be eliminated.

PMID- 12523773
TI  - Risk evaluation for pathogenic bacteria and viruses in sewage sludge compost.
AB  - Composting can be regarded as the most available option for recycling of sewage
      sludge. However, the existence of pathogenic bacteria and viruses in the compost
      has been scarcely investigated until now. So there is little information on the
      infectious risk through agricultural activities or gardening in using the
      compost. In this study, several kinds of composts were investigated for detection
      of pathogenic bacteria (Salmonella spp. and Escherichia coli O157) and enteric
      viruses. It was concluded from the result that these bacteria and viruses could
      not be detected in 1.0 g-wet of any kinds of composts. Infectious risks through
      agricultural activities or gardening were evaluated by Monte Carlo simulation in
      the case that the compost was polluted by Salmonella spp., E. coli O157:117 and
      Poliovirus 1. Criteria satisfying the acceptable risk (less than 10(-4) per year)
      for these pathogenic bacteria and virus in the compost were determined from the
      result of simulations. 1.0 [CFU or PFU/g-wet] was available as the criteria for
      E. coli O157 and Poliovirus 1 in the compost. On the other hand, the criterion
      for Salmonella spp. in the compost should be established on a lower concentration
      than 0.001 CFU/g-wet.

PMID- 12523774
TI  - Toxicity assessment of 255 chemicals to pure cultured nitrifying bacteria using
      biosensor.
AB  - The bioassay has been attracting attention as a method of toxicity assessments of
      micropollutants in the environment. In this study, we report the characteristics
      (selectivity and sensitivity) of the nitrifying bacteria biosensor for 255 kinds
      of chemicals as a model of chemical contaminant in the environment and the
      results of evaluation of mixed samples of several substances. In the nitrifying
      bacteria respiration inhibition test using the biosensor, 56 chemicals were
      detected. It was found that this biosensor is especially sensitive to seven
      chemicals that have a thiocarbonyl functional group (>C=S), such as a thioamide
      group of thiocarbamate group. These chemicals are considered to specifically
      inhibit AMO by chelation of copper. The samples consisted of a mixture of seven
      types of anilines that inhibit respiration in the bacteria, a mixture of five
      types of chlorophenols, and a mixture of eight types of substances that contain
      thiocarbonyl groups were examined. All of the mixed samples inhibited the
      respiration of the nitrifying bacteria more than 10% by the inhibition rate, and
      observed a synergistic effects of the substances in the samples.

PMID- 12523775
TI  - Development of rapid in vitro assay for oxidative liver injury and its
      application to 230 chemicals.
AB  - Water environments are thought to be polluted with thousands of synthetic
      chemicals and biproducts involving persistent organic pollutants and endocrine
      disrupters, and their human and ecological impacts are causing serious anxiety.
      Many bioassays have been undertaken to evaluate the hazardous impacts of toxic
      chemicals dissolved in water. Reactive Oxygen Species (ROS) are well known to be
      involved in the toxicity of various chemicals. ROS are mostly generated in liver
      and cause oxidative damage to DNA, lipids and proteins, resulting in the failure
      of cellular functions. In order to develop an in vitro bioassay system to
      estimate ROS induced liver toxicity by chemicals, we investigated the lipid
      peroxidation, liver cell injury, and genotoxicity using the human hepatocellular
      carcinoma cell line, Hep-G2 (ATCC HB 8065), and applied it to 230 chemicals.

PMID- 12523776
TI  - Toxicity assays to determine the start-up strategy for an anaerobic sequencing
      batch reactor (anSBR).
AB  - Addition of glucose as the co-substrate and the use of a water-based polymer to
      enhance granulation were studied with the aim of shortening the start-up period
      of an anSBR (anerobic sequencing batch reactor) for high-strength industrial
      wastewater treatment. An initial start-up feed composition consisting of 70%
      sucrose and 30% industrial wastewater was favorable to reduce the start-up time.
      Increase in the average particle size and reduction in settled supernatant
      turbidity was observed with increased water-based polymer addition up to a
      concentration of 0.1 m/L. Polymer dosages above 0.1 ml/L were undesirable as big
      and "flaky" flocs were formed which prevented the flocs from settling quickly.
      Addition of 0.005 ml/L to 0.1 ml/L polymer to the mixed liquor had no observable
      adverse effects on the anaerobic biomass metabolism. Instead, the addition of the
      polymer appeared to improve biogas production and had an overall positive effect
      on anSBR performance treating the industrial wastewater.

PMID- 12523777
TI  - Comparison of yeast-based estrogen receptor assays.
AB  - In order to quantitatively compare measurement methods used to evaluate
      estrogenic activity in environmental samples, 13 substances and sewage samples
      were measured using three methods that employ recombinant yeast to measure such
      estrogenic activity. The estrogenic activity of the chemical substances confirmed
      a correlation between the three measurement methods. Two methods failed to
      measure estrogenic activity in some of the sewage samples because the yeast
      growth was inhibited. But the one remaining method was able to estimate the
      estrogenic activities of all sewage samples without the inhibition of the yeast
      growth. Similar correlation was observed between the methods for the estrogenic
      activities of the final discharge that was measured.

PMID- 12523778
TI  - Preservation of human cell bioassay device for the on-site evaluation of
      environmental waters.
AB  - We have already developed a novel disposable bioassay device based on the low
      density lipoprotein (LDL) uptaking activity of human hepatoblastoma Hep G2 cells
      in our previous work. However, this device is not readily applicable to evaluate
      river water toxicity on-site because it cannot be preserved for more than one
      week. In this work, we developed the method for preservation of the device to
      enable it to be preserved for at least one month. The device can be supplied to
      individual environmental sites without any facilities for cell culture. We can
      evaluate river water toxicity by 2 hours of exposure after thawing. Therefore,
      this kind of device could be a promising tool for daily water quality management.

PMID- 12523779
TI  - Estrogen-like effect and cytotoxicity of chemical compounds.
AB  - Luciferase assay, cytotoxicity test and protein quantitative analysis were
      performed after the exposure of chemical compounds to MVLN cells that are
      utilized to detect the endocrine disrupting activity. These consequences indicate
      that the concentration is different between the estrogen receptor mediated
      proliferation of breast cancer cells and the estrogen receptor mediated
      transcription by chemical compounds.

PMID- 12523780
TI  - Evaluation of estrogen-like activity on sewage treatment processes using
      recombinant yeast.
AB  - Four sewage treatment plants based on an activated sludge process and a pilot
      scale plant for advanced sewage treatment located in Japan were evaluated for
      removal of estrogenic substances using in vitro recombinant yeast assay and
      chemical analysis. The results indicated that 17beta-estradiol (E2) significantly
      contributed to estrogen-like activity analyzed by yeast assay especially in
      secondary treated effluents. On the other hand, batch study showed that estrogen
      like activity of spiked E2 was easily decreased by an activated sludge treatment.
      This result suggested that E2 concentrations measured by enzyme immunoassay (EIA)
      were interpreted as false positives in effluents, and that unknown estrogenic
      substances other than E2 might have contributed to estrogen-like activity in the
      secondary treated effluents. Further, in the pilot scale study, advanced sewage
      treatment processes such as a biological aerated filtration (BAF) process, an
      advanced oxidation process (AOP), were effective for the removal of those
      estrogenic activities contributed by unknown estrogenic substances in sewage
      secondary treated effluent.

PMID- 12523781
TI  - Arsenic contamination in groundwater of Samta, Bangladesh.
AB  - In March 1997, we analyzed the water of all tubewells used for drinking in Samta
      village in the Jessore district, Bangladesh. It has been confirmed from the
      survey that the arsenic contamination in Samta was one of the worst in the Ganges
      basin including West Bengal, India. 90% of the tubewells had arsenic
      concentrations above the Bangladesh standard of 0.05 mg/l. Tubewells with higher
      arsenic concentrations of over 0.50 mg/l were distributed in the southern area
      with a belt-like shape from east to west, and the distribution of arsenic
      concentration showed gradual decreasing toward northern area of the village. In
      order to examine the characteristics of the arsenic distribution in Samta, we
      have performed investigations such as: 1) the characteristics of groundwater
      flow, 2) the distribution of arsenic in the ground, 3) the concentration of
      arsenic and the other dissolved materials in groundwater, and 4) the distribution
      of arsenic concentration of trivalence and pentavalence. This paper examines the
      mechanism of arsenic release to groundwater and explains the above-mentioned
      characteristics of the arsenic contamination in Samta through the investigations
      of the survey results for these years.

PMID- 12523782
TI  - The quantification and characterization of endocrine disruptor bisphenol-A
      leaching from epoxy resin.
AB  - Bisphenol-A (BPA), a known endocrine disruptor, is a main building block of epoxy
      resin which has been widely used as a surface coating agent on residential water
      storage tanks. Therefore, BPA leaching from the epoxy resin can adversely affect
      human health. In this study, BPA leaching from three epoxy resins were quantified
      at 20, 50, 75 and 100 degrees C both in deionized water and the specified test
      water, respectively. BPA leached to the test water was identified using GC-MS and
      quantified with GC-FID after a sequential extraction and concentration. The
      results showed that BPA leaching has occurred in all three samples tested. The
      quantity of BPA from unit area of epoxy resin coating was in the range of 01.68
      273. 12 microg/m2 for sample A, 29.74-1734.05 microg/m2 for sample B and 52.86
      548.78 microg/m2 for sample C depending on the test temperature, respectively. In
      general, the amount of BPA leashing increased as the water temperature increases.
      This result implies a higher risk of BPA leaching to drinking water during a
      summer season. In addition, microbial growth, measured by colony forming units,
      in epoxy coated water tanks was higher than that in a stainless steel tank. The
      results suggest that compounds leaching from epoxy resin may support the growth
      of microorganisms in a residential water holding tank.

PMID- 12523783
TI  - Removal of mutagen precursor from wastewater by activated sludge and oxidation
      treatment.
AB  - Removal of mutagen precursors from wastewaters was investigated. Removal extent
      of mutagen precursor was evaluated by the mutagen formation potential (MFP) which
      is mutagenicity of pollutants capable of forming mutagens when chlorinated under
      the conditions of water purification processes. 77% of the MFP reduction extent
      for a wastewater from a university was achieved by activated sludge treatment.
      However, no significant reduction of the MFP was observed for wastewater from
      food industry, a landfill leachate and mold extract. The Fenton oxidation
      treatment and ozone treatment are able to remove mutagen precursors from the mold
      extract and the wastewater from a university, respectively. 90% of the MFP
      reduction extent was achieved for the mold extract by the Fenton treatment. 54%
      of the MFP reduction extent was achieved for a sewage by the ozone treatment.
      Using the oxidation treatments, biodegradability of mutagen precursors in the
      mold extract and sewage was improved. From the viewpoint of treatment cost, the
      oxidation treatments should be oriented to the improvement of biodegradability.

PMID- 12523784
TI  - The mutagenicity of amino-derivatives of diphenyl ether herbicides in new
      Salmonella typhimurium YG tester strains.
AB  - In this study, we examined the mutagenicity of four diphenyl ether herbicides and
      their amino derivatives in Salmonella typhimurium TA tester strains and YG tester
      strains. YG tester strains have been newly developed for sensitive detection of
      specific chemicals. S. typhimurium YG 1021, YG 1024, YG 1026 and YG 1029 strains
      are sensitive to mutagenic nitoroarenes and hydroxyamines. S. typhimurium YG 3003
      is a strain that is sensitive to some oxidative mutagens. And S. typhimurium YG
      7108 is useful for detection of mutagenic alkylating agents. As a result, each
      amino derivative of diphenyl ether herbicides is more mutagenic than its parent
      herbicide in S. typhimurium TA and YG tester strains with metabolic activation by
      S9 mixture. Moreover, S. typhimurium YG tester strains are more useful for highly
      sensitive detection of mutagens than S. typhimurium TA tester strains. We also
      examined the production of amino derivatives in a water environment from parent
      herbicides. It was clear that diphenyl ether herbicides rapidly transform to
      amino derivatives in a water environment.

PMID- 12523785
TI  - Trihalomethane formation potentials of organic pollutants in wastewater
      discharge.
AB  - Drinking water resources contaminated by wastewater discharge could have great
      risk of trihalomethane (THM) formation upon chlorine disinfection during
      treatment. In the present study, THM formation potentials (THMFP) of the organic
      pollutants in the raw sewage and treated secondary effluent collected from f ull
      scale wastewater treatment plants were characterised. The organic matter
      remaining in the secondary effluent had higher unit carbon THMFP in comparison
      with that in the raw sewage. However, owing to removal of organic pollutants in
      the treatment works, the overall THMFP of the wastewater was reduced
      significantly throughout the biological treatment process. Using XAD-8 resin,
      organic materials in the wastewater samples were separated into hydrophobic and
      hydrophilic fractions. Hydrophobic organic, which possesses higher THMFP than
      hydrophilic organic, was the predominant THM precursor in wastewater discharge.
      Ozonation could be used to alter the properties of organic matter, particularly
      the hydrophobic fraction, and reduce its THMFP.

PMID- 12523786
TI  - Pollutant runoff from non-point sources and its estimation by runoff models.
AB  - In order to attain a sound and sustainable water environment, it is important to
      carry out the environmental management of the watershed. For this purpose,
      knowledge on the pollutant runoff mechanism from non-point sources becomes very
      important especially under rainy conditions. At Isahaya, Nagasaki, Japan, a big
      project of construction of sea-dyke and reclamation is now going on, so reducing
      the pollutant runoff, especially from non-point sources, becomes more important.
      Some runoff models of rainwater are developed to predict the rate of pollutant
      loads from the non-point sources, and their results are compared with each other
      to investigate the accuracy of prediction. In this paper, runoff analysis of both
      rainwater and pollutants has been carried out using three models: the tank model,
      the kinematic wave (K-W) model, and a model using the digital elevation model
      (DEM). For precise estimation, it becomes necessary to identify the parameters
      included in these models. Here, total nitrogen has been considered as pollutants,
      and detachment rates are evaluated, correlated with a class of land use, soil
      type, and moisture content. Finally, it has been shown that pollutant runoff from
      non-point sources can be predicted fairly well, identifying the model parameter
      appropriately.

PMID- 12523787
TI  - Dynamic behavior of suspended pollutants and particle size distribution in
      highway runoff.
AB  - Continuous runoff quality monitoring was conducted for one month at urban highway
      drainage with an area of 8.4 ha. Dynamic change of suspended solids and heavy
      metal concentrations were investigated during first flush periods, taking the
      particle size distribution into consideration. Except for Pb, the concentrations
      of TSS and heavy metals in runoff were within the range of the EMC reported in
      recent highway runoff research. Particle-bound heavy metals (Zn, Pb, and Cu)
      accounted for more significant pollutant loads than soluble fractions. Their
      content decreased with increasing total SS concentration in runoff samples. The
      results of particle size distribution (PSD) analysis of runoff samples indicate
      that high TSS concentration samples contained coarser particles. Based on the PSD
      results, a stepwise wash-off phenomenon of TSS under varying runoff rate
      conditions was explained by the different washoff behavior of fine (< 20 microm)
      and coarser particles.

PMID- 12523788
TI  - Monitoring of shallow sea environment by using snapping shrimps.
AB  - We examine the validity of pulse count of snapping shrimps for sea environmental
      monitoring. Snapping shrimps, which make a peculiar pulse sound, are found
      everywhere in the world. Pulse count can be achieved merely by recording their
      sounds for a few minutes by using a hydrophone without special biological
      knowledge. From field surveys and laboratory experiments, we found that the pulse
      count depends on water temperature when sea environment is normal, and it falls
      due to the occurrence of oxygen-deficient water. The results show that this
      method can be a useful index of the effect of water pollution on benthic animals
      in fixed-point observation.

PMID- 12523789
TI  - Measurement of color degree with Dilution method.
AB  - A new method, named the "Dilution method", is proposed to express the color of
      water. This method is based on the idea to define a color degree with the
      dilution times when it is hard to distinguish any difference between diluted
      colored water and distilled water as a standard. The Dilution method has the
      merits of a simple operation and wide applicability to any colored waters.
      Moreover, the results of the Dilution method are more understandable and
      sensitive than those of other conventional measurement methods.

PMID- 12523790
TI  - Use of nitrogen stable isotope ratio of periphyton for monitoring nitrogen
      sources in a river system.
AB  - In order to confirm the usefulness of the N stable isotope ratio of periphyton
      (mainly composed of attached algae) as an indicator for monitoring the N sources
      in river watersheds, we measured the isotope ratio of periphyton along the
      Chikuma River. In the river, both the concentrations of dissolved total nitrogen
      (DTN) and the delta15N values of periphyton increased downstream. Specific
      nitrogen loading rates (SNLR) calculated from administrative data also showed an
      increase downstream from 7 to 11 kg N ha(-1) yr(-1), with the increasing
      contribution by sewage and livestock waste from 6 to 40% to total N loading.
      There are significant positive relationships between the DTN concentration and
      the SNLR (r2=0.54, P<0.05), and the delta15N values of periphyton and the SNLR
      (r2=0.78, P<0.05). The increase in DTN concentration reflected the increase in
      input of N loading. The increase in delta15N of periphyton might reflect the
      increase in relative contribution by sewage and livestock waste down the river,
      especially the increase in sewage. The present study indicates the usefulness of
      the N stable isotope ratio of periphyton as an indicator for monitoring N sources
      in a river system.

PMID- 12523791
TI  - A model for predicting sediment-water partition of toxic chemicals in aquatic
      environments.
AB  - In order to investigate the characteristics of sediment-water partition of
      chemicals in aquatic environments using published data, we developed a model for
      predicting the sediment-water partition coefficient (Kp) as the sum of sorption
      to sediment organic matter and sorption to sediment inorganic matter. This model
      is so successful that the differences between Kp (median for a variety of
      Japanese water bodies) and pre-Kp (predicted K) are within one order of magnitude
      in 24 out of 28 chemicals.

PMID- 12523792
TI  - Seasonal variations in growth rate of phytoplankton in Hakata Bay, Japan.
AB  - Recently, water pollution with high concentrations of organic matter has occurred
      frequently in Hakata Bay. It is said that a high level of primary production
      provides much organic matter and affects water quality of the bay, and it is
      proved by the appearance of phytoplankton throughout the year. In this study, we
      simulated variations of phytoplankton population with a box-type model using
      monthly data in a long-term measurement and we analyzed the final growth rate
      changes of phytoplanktons that explain the conditions for its appearance.
      Consequently, we found that the final growth rate varies with pattern of half
      year periodicity and water temperature and/or ambient nutrient controls the final
      growth rate to be low every January and July.

PMID- 12523793
TI  - Mass balance of a wastewater loaded canal system: case study of Bangkok.
AB  - A dynamic water quality model was applied in order to investigate self
      purification processes in highly loaded canals in the centre of Bangkok, capital
      city of Thailand. Oxygen production by aquatic plants induces a significant
      diurnal variation of the dissolved oxygen concentration. The corresponding
      profiles of heterotrophic growth and BOD5 concentration demonstrate the limiting
      impact of oxygen shortage during night time. Both self-purification mechanisms-
      biological degradation and settling--are considered and water-sediment
      interactions are calculated. Simulation results and measurement data are
      summarized by mass balance schemes which offer a telling characterization of the
      complex system.

PMID- 12523794
TI  - Study on generation of oxygen-depleted water based on stochastically changing
      solar radiation intensity.
AB  - To examine the generation probability of oxygen-depleted sea water in Hakata Bay,
      possible 20 time-series of different hourly-solar-radiation intensities were
      generated stochastically, and a numerical simulation on dissolved oxygen was
      carried out for each time series. The results of the model calibration followed
      the seasonal variation of observed water quality well, and generated cumulative
      frequency-distribution curves of daily solar radiation agreed well with the
      observed ones. The simulation results indicated that the exchange of sea water
      would have a great influence on the DO concentration, and that the concentration
      could change more than 1 mg/L in a day. This prediction method seems to be an
      effective way to examine a solution to minimize fishery damages when DO is
      depleted.

PMID- 12523795
TI  - Characterization of natural organic matter in a shallow eutrophic lake.
AB  - Natural organic matter (NOM) from five sampling stations of a shallow, eutrophic
      lake, Lake Kasumigaura was analyzed in four different seasons of a year by
      several NOM characterization methods including GPC and pyrolysis GC/MS with the
      objective of elucidating its characteristics as well as studying its temporal and
      spatial changes. A comparison was also made among the characteristics of NOM from
      this and two other lakes. The study showed that NOM in Lake Kasumigaura had
      comparable DOC, UVA260, and THMFP with that of Lake Inbanuma, but much higher
      than that of Lake Tsukui. Both molecular weight and polydispersities remained
      similar among those three sources but these values were significantly smaller in
      comparison with Suwannee River NOM. The similarity index analysis based on
      pyrochromatograms was useful to evaluate spatial and seasonal changes in NOM
      characteristics. Distinctive characteristics of NOM at KS1 (station near the
      mouth of Sakura River) were better explained by the difference in
      pyrochromatograms rather than in general water quality. Except for KS1, the
      change in NOM characteristics in the lake water was found to be more pronounced
      in different seasons than at different locations.

PMID- 12523797
TI  - Corporate initiatives in ergonomics.

PMID- 12523796
TI  - Spatial and dynamic simulation for Miyun Reservoir waters in Beijing.
AB  - In order to assist the water quality management in Miyun Reservoir, a spatial and
      dynamic simulation model system was built. In the model system, GIS was
      integrated with the WASP5 model. The integrated model system was then calibrated
      and verified in different sets of field data. The result showed that the
      integrated model system could characterize the Miyun Reservoir waters. Two
      scenarios were then designed and analyzed with the integrated model system. It
      was indicated that the water quality would improve if the cage fishery was
      banned, the algae blooms might occur in Miyun Reservoir if the low water stage
      ocurred but loads remained unchanged.

PMID- 12523798
TI  - Corporate initiatives in ergonomics--an introduction.
AB  - Examples in the literature of corporate initiatives in ergonomics are reviewed.
      Different types of programmes are identified with ambitions ranging from time
      limited interventions to continuous processes. Common elements are health
      surveillance, workstation design and choice of tools, product design, quality
      aspects, participative aspects and education, training and information. The
      implementation of ergonomics programmes varies substantially depending on the
      type of company, and company policies and organisation. Some of the most
      developed ergonomics programmes originate from the automobile industry. Other
      businesses with many established programmes are the electronics industry, the
      food industry and the office environment. A participative approach, as well as
      ergonomics expertise, are crucial ingredients for a successful programme. The
      scientific evaluation of ergonomics programmes, especially in economical terms,
      is in too many cases insufficient or missing. Furthermore, links to company core
      values such as quality improvement are often lacking. Programmes in ergonomics
      are still often seen as solely a matter of health and safety. Only a few
      companies have reached the state where ergonomics constitutes an integrated part
      of the overall strategy of the enterprise.

PMID- 12523800
TI  - Corporate ergonomics programme at Ford Motor Company.
AB  - The use of ergonomic principles in automobile assembly and manufacturing
      operations has become an important part of a comprehensive health and safety
      process as well as an integral part of the engineering systems. Ford Motor
      Company has developed an ergonomics process to manage issues related to injury
      and illness (e.g., musculoskeletal diseases) and to ensure the appropriate use of
      human resources on the plant floor. The ergonomics programme uses joint labour
      and management teams to identify and evaluate jobs and develop and implement
      solutions. This paper summarises the efforts of the Ford Motor Company in
      implementing and maintaining the programme. Key strategies are outlined that
      provide important links to internal organisational units that are critical to
      fully utilise the ergonomics process. In addition, the paper outlines differences
      between proactive and reactive efforts and shows the importance of using the
      information generated by the initiatives for process improvement.

PMID- 12523799
TI  - Corporate ergonomics programme at Volvo Car Corporation.
AB  - One of Volvo Car Corporation's core values is "Environmental Care". Volvo Cars
      has a tradition of attention to the work environment and has over the years
      developed a working environment management system, an organisational strategy for
      the participation of everyone, a working environment policy,
      standards/specifications and methods for efficient practical performance. The
      Production Ergonomics Project is an example of this. In order to achieve results
      in ergonomics one has to work comprehensively, which means working with the
      product, the process, the workplace, the individuals and the work organisation.
      The key to success is to train all categories concerned in load ergonomics and to
      perform methodical ergonomic work through the whole chain from design to
      production.

PMID- 12523801
TI  - Corporate ergonomics programme at automobiles Peugeot-Sochaux.
AB  - An ergonomic assessment tool for design procedures, exclusive to Peugeot-Citroen,
      called ECM, was developed and applied at the design stage by method technicians
      in the 1990s. It generates data, which are followed up by the project leader of a
      new model and ergonomists until two years before each launch. During this time,
      vehicle design is subject to modification, to adapt to ergonomic demands.
      Simplified methods (DACORS and METEO) were also developed to assess workstations
      on the shop floor in trim and final plants. Assessments were used to grade the
      workstations into four profiles linked to physical and static requirements.
      Production technicians are responsible for the application of these local methods
      on the shop floor. The management of these centres aimed to reduce the risks of
      musculoskeletal disorders by reduced heavy profiles of these stations. New cases
      of musculoskeletal disorders, surveyed by the company doctor among workers on the
      assembly lines had decreased since 1996. In 1999, the incidence increased again,
      despite the pursuit of ergonomic methods. This increase in musculoskeletal
      disorders was above all linked to a major reorganisation of work conditions,
      including a reduction in the cycle time on the assembly line, and to a move into
      a new workshop.

PMID- 12523802
TI  - Corporate ergonomics programme at Scottish & Newcastle.
AB  - Partly as a result of impending EU Legislation in 1992 (six pac) an Ergonomics
      Adviser was employed by the Occupational Health & Safety Services within Scottish
      & Newcastle to assist with the ergonomic considerations inherent within these
      Regulations. Although employed initially to address the manual handling issues
      within the beer delivery operations, the role of the Ergonomist has evolved to
      provide support and advice in many of the corporate programs aimed at improving
      employee health and safety. This paper describes three such programs; namely
      those of manual handling, display screen equipment and occupational stress.
      Detailed cost-benefit analysis information, highlighting a 1.3 Million pounds
      sterling (stg) reduction in associated costs, is described in relation to the
      first of these programs. The latter two programs have not yet been in situ for a
      suitable duration to enable such cost-benefit analyses.

PMID- 12523803
TI  - Corporate ergonomics programme at BCM Airdrie. Boots Contract Manufacturing.
AB  - The production processes at the BCM Airdrie site range from manual loading tasks
      in the manufacturing areas to high frequency packaging assembly tasks on the
      production lines. Both are jobs that are known to carry risk to musculoskeletal
      health, so an ergonomist was appointed to design and co-ordinate an ergonomics
      programme for the site to control these risks. This paper details the programme
      that has evolved to proactively manage musculoskeletal risks in the design of
      both new and existing equipment and processes. The ergonomics procedures
      described primarily involve the engineers from all areas of the factory, and the
      process for ergonomics involvement with engineering design projects is described.
      Shop-floor personnel involvement is considered to be an essential part of the
      programme and 'Ergonomics Champions' are being trained on the packing lines to
      monitor the risks that are sometimes introduced with the different designs of
      product packaging.

PMID- 12523804
TI  - Hand-transmitted vibration from the steering wheel to drivers of a small four
      wheel drive tractor.
AB  - The paper presents research results of the vibration transmitted from the
      steering wheel of the small tractor with a 4-wheel drive to the driver's hands.
      The vibration measurements were carried out on the tractor randomly chosen from
      the producer's store-house. Before testing the tractor was examined and adjusted
      following the producer's recommendations. The vibration levels were measured at
      idling and at full load. The vibration level on the steering wheel was measured
      and analyzed and the frequency spectra for the chosen working conditions were
      obtained. The frequency-weighted acceleration, given in m/s(-2), was calculated.
      The vibration total value was defined as the root-mean-square of the three
      component values. The obtained values are graphically represented in accordance
      with ISO/DIS 5349-1979 and ISO5349-1-2001. The vibration exposure for the
      predicted 10% prevalance of vibration-induced white finger in accordance with
      Annex C of the same standard was also tested.

PMID- 12523805
TI  - Field evaluation of two commonly used slipmeters.
AB  - A variety of slipmeters have been used to assess the slipperiness of floor
      surfaces. International standards for the operation of slipmeters describe the
      protocol for a single measurement. These standards usually do not cover some of
      the critical elements in safety assessment such as methods for the selection of
      measurement locations and the necessary number of repeated measurements at each
      location. Furthermore, most of the slipmeters were evaluated in laboratory
      settings with new floor surfaces and artificial contaminants. Two commonly used
      slipmeters, the Brungraber Mark II and the English XL, were evaluated at actual
      worksites in this experiment. Four floor tiles in each of four different work
      areas in the kitchens of 18 fast food restaurants were selected for repeated
      measurements with these two slipmeters. The results indicated that sanding of
      footwear materials has a significant effect on the outcomes of friction
      measurements, and the tile-to-tile variations in friction in the same areas of
      restaurants were also mostly statistically significant. Significant local
      variation in friction among tiles in the same area could potentially increase the
      chances of slip and fall incidents. Both slipmeters used in this experiment could
      potentially have problems in the areas with grease, such as grill and fryer
      areas, since the build-up of grease during repeated strikes could alter the
      outcome of friction measured.

PMID- 12523806
TI  - Movement compatibility for rotary control and circular display--Computer
      Simulated Test and real Hardware Test.
AB  - This experiment studied strength and reversibility of direction-of-motion
      stereotypes and response times for different configurations of circular displays
      and rotary knobs. The effect of pointer position, instruction of turn direction,
      and control plane on movement compatibility was analyzed with precise
      quantitative measures of strength and reversibility index of stereotype. A
      comparison of results was made between a Computer Simulated Test and a Hardware
      Test with real rotary controls. There was consensus in the results of the two
      tests that strong and significantly reversible clockwise-for-clockwise (CC) and
      anticlockwise-for-anticlockwise (AA) stereotypes were obtained at the 12 o'clock
      position. Subjects' response times were found to be generally longer when there
      were no clear movement stereotypes. Nevertheless, differences of results were
      observed that while the CC and AA preferences were found to be dominant and
      reversible at all the planes and pointer positions in the Hardware Test, there
      was variation in the strength and reversibility of the two stereotypes amongst
      different testing configurations in the Simulated Test. This phenomenon was
      explained by the operating of the clockwise-for-right and anticlockwise-for-left
      principles, as shown in the analysis of contributions of component principles to
      the overall stereotype. The differences of results from the two tests were
      discussed with regard to simulation fidelity and it was suggested that a real
      Hardware Test should be used whenever possible for determination of design
      parameters of control panels in consideration of movement compatibility. Based on
      the Hardware Test, a pointer is recommended to be positioned at 12 o'clock
      position for check reading or resetting purpose, and the frontal plane is the
      best plane for positioning a rotary control with circular display. The results of
      this study provided significant implications for the industrial design of control
      panels used in man-machine interfaces for improved human performance.

PMID- 12523807
TI  - Filling 'gaps' in strength data for design.
AB  - Data on the physical strength capabilities of users are fundamental to the safe
      and usable design of products. It is recognised, however, that there are many
      'gaps' in the ergonomics data available to designers. Whilst considerable
      research on human capabilities and limitations has already been carried out, few
      data exist which are directly applicable in the design process. This paper
      describes a two-stage research project which was undertaken to try to address
      some of these data 'gaps'. Potential needs for design-relevant data were
      identified in Stage 1 of the research and in Stage 2 new data were collected to
      meet some of those needs. Data were collected on children through to the older
      adult on a series of six strength measurements, all of which were intended to be
      directly applicable to design: (1) finger push strength, (2) pinch-pull strength,
      (3) hand grip strength, (4) wrist-twisting strength, (5) opening strength, and
      (6) push and pull strength. The methodology, findings and data from this research
      are presented and discussed.

PMID- 12523808
TI  - Manual handling injury in a disability services setting.
AB  - Approximately 2700 manual handling injuries recorded among disability services
      workers in an Australian state government agency between 1997 and 2000 were
      analysed to identify high-risk groups and leading causes to be targeted for
      prevention. Client support, including assisting clients into and out of bed and
      holding clients during epileptic seizures, had the highest cause-specific injury
      rate per 100 full-time equivalents (12.2, 95% confidence interval (CI) 6.2-20.2).
      Women had significantly higher rates than men, an average of 29.8 (95% CI 19.9
      41.7) compared with 16.6 (95% CI 9.5-25.7). Gender (being female) and low job
      classification significantly increased the odds of an injury resulting in time
      off work. Only gender significantly predicted the likelihood of high compensation
      payments. Together with the surveillance data, responses to the questionnaire
      survey of 120 workers indicate a need for effective ergonomics intervention.

PMID- 12523809
TI  - Study of twenty-seven paediatric patients with open tibial fracture: the role of
      definitive skeletal stabilisation.
AB  - BACKGROUND: The aim of this retrospective study was to review our practice of the
      management of open tibial fractures in children. METHODS: Twenty-seven children
      aged 3-15 years (mean 9.5) with open fractures of the tibia were treated with
      early aggressive wound debridement and lavage. Gustilo grading was used. The
      wounds were graded as follows: I (13 patients), II (6 patients), IIIa (3
      patients), IIIb (5 patients). Open wounds were treated as appropriate, 30% of
      patients required a plastic surgical procedure. RESULTS: Five patients were
      treated by initial external fixation of the tibia; the remainder was treated by
      cast immobilisation. The mean period for fracture healing was 6 months (1.5-48
      months). There were no cases of non-union or deep infection. The incidence of
      complications where external fixation was applied was significant: one malunion
      required osteotomy, there were 2 cases of delayed union and four cases of pin
      track infection. In the group treated in casts, the most significant complication
      was loss of reduction of the fracture (five cases), requiring conversion to
      external fixation in 2 and screw and wire fixation in another; the remaining
      cases of displaced fractures responded to re-manipulation and plaster
      application. CONCLUSIONS: We conclude from our results hat majority of isolated
      open tibial fracture in children can be treated by wound debridement and plaster
      cast immobilisation. There is still a role for the use of external fixation
      especially where there is a grossly unstable fracture or extensive soft tissue
      injury requiring a flap procedure.

PMID- 12523810
TI  - Initial experience of using color kinesis in the diagnosis of coronary artery
      disease.
AB  - BACKGROUND: Color kinesis (CK) is a recently developed echocardiographic
      technique. This report describes our initial effort in the validation of the use
      of CK for the diagnosis of coronary artery disease (CAD). METHODS: Two
      dimensional (2-D) echocardiography and CK were studied in 30 normal subjects and
      24 CAD patients. Coronary angiography was performed in the 24 patients.
      Significant (> 70% luminal diameter stenosis) CAD was present in 18 patients
      (79%), all of whom had history of myocardial infarction. Regional fractional area
      change in each segment was displayed as a stacked color histogram. The histograms
      derived from these 30 normal subjects were averaged to obtain the normal pattern
      of left ventricular contraction; the mean value +/- 1 SD was considered the
      reference histogram. When the regional fractional area change deviated from this
      normal reference, this segment was considered as having regional wall motion
      abnormality. The detection of wall motion abnormalities by visual interpretation
      of 2-D echocardiography, reviewing the CK loop recording, and CK stacked
      histograms were compared. To assess the relationship of measurement of
      endocardial excursion of CK images, the width of the color band was measured at
      the midpoint of each segment along a line perpendicular to the cardiac border.
      The endocardial excursion measured by 2 independent observers was compared using
      linear regression analysis and calculation of intraclass correlation coefficient.
      RESULTS: The sensitivity and specificity for detection of CAD were 77.8% and
      66.6%, respectively, for CK loop reviewing, 83.3% and 66.7% for CK stacked
      histogram analysis, and 77.8% and 83.3% for 2-D echocardiography. The overall
      accuracies for CAD detection were 75% for CK loop reviewing, 79.2% for CK stacked
      histogram analysis, and 79.2% for the 2-D echocardiography (not significant in
      all comparisons). The correlation of measurement of endocardial excursion from
      the CK images by 2-observers was good (r = 0.85, p < 0.01), and intraclass
      correlation coefficient was 0.99 (p < 0.0001). CONCLUSIONS: Our data demonstrate
      that both the CK loop reviewing and stacked histogram analysis were comparable to
      2-D echocardiography for detecting CAD.

PMID- 12523811
TI  - It is difficult to eradicate Helicobacter pylori from dental plaque by triple
      therapy.
AB  - BACKGROUND: Dental plaque has been suggested as a permanent reservoir of
      Helicobacter pylori (H. pylori) and a potential source of reinfection. The aims
      of this study were to investigate the presence of H. pylori in both dental plaque
      and the stomach and to evaluate the therapeutic effect of triple therapy on H.
      pylori in dental plaque. METHODS: Dental plaque and gastric biopsy samples were
      obtained from 65 patients with dyspeptic symptoms for endoscopic examination. The
      prevalence of H. pylori in dental plaque and stomach was determined with rapid
      urease test, histologic examinations and polymerase chain reaction assay based on
      the primer pair derived from the cagA gene of H. pylori. Triple therapy was
      administered to patients infected with H. pylori. H. pylori status was re
      evaluated after eradication therapy. RESULTS: Prior to treatment, H. pylori was
      found in the stomach in 38 of 65 (58%) patients and in dental plaque in 28 of 65
      (43%) patients. The coexisting infection rate of H. pylori in both stomach and
      dental plaque was 74%. After triple therapy, H. pylori was eradicated from the
      stomach in 32 of 38 (84%) patients, but only 2 of 28 (7%) patients with
      coexisting H. pylori infections of stomach and dental plaque showed the
      elimination of H. pylori from dental plaque. CONCLUSIONS: The high coexisting
      infection rate of H. pylori in both stomach and dental plaque implies that dental
      plaque can serve as another reservoir of H. pylori. H. pylori in dental plaque
      was hardly eradicated by triple therapy. Dental plaque may be a potential source
      for recrudescence of gastric infection after successful systemic therapy.

PMID- 12523813
TI  - Canine pancreas allotransplantation with enteric drainage.
AB  - BACKGROUND: Before embarking on a clinical human pancreas transplantation program
      we sought a canine animal model with enteric drainage to refine our technical
      skills, to evaluate the surgical risks and to study the rejection pictures under
      modern triple immunosuppression therapy. METHODS: Twenty donor-recipient pairs of
      unrelated mongrel dogs underwent pancreaticoduodenal allotransplantation with
      enteric drainage. All dogs were immunosuppressed by triple therapy with
      prednisolone, cyclosporine (Neoral) and mycophenolate mofetil (MMF). Rejection
      grade and surgical risk were evaluated. RESULTS: Group 1 included 10 (50%) dogs
      surviving at least 14 days. In group 2 surviving less than 14 days, the median
      survival was 5.5 days, ranging from 1 day to 13 days. The most common
      complications were duodenal stump leakage and wound infection. Duodenal stump
      leakage eventually led to mortality in 3 dogs of group 2. Two (in group 2) of the
      3 wound infections became too severe to control and caused death. There were 2
      dogs complicated with graft necrosis and 2 with graft vascular thrombosis
      individually, which all resulted in death. Other fatal complications included 1
      chyle leakage, 1 intraabdominal abscess and 1 pneumonia individually. Ninety
      percent in each group developed rejection. Severe rejection developed in 5 (50%)
      dogs in group 2 (grade 4 and 5), p = 0.033, as compared with none in group 1. The
      rejection in most cases (90%) of group 1 was mild to moderate, with 4 grade 3, 3
      grade 2 and 2 grade 1. CONCLUSIONS: Canine pancreas allotransplantation with
      enteric drainage is a feasible animal model to achieve survival longer than 14
      days in 50% cases studied. Duodenal stump leakage was the most common fatal
      complication in this model. Severity of rejection was closely associated with
      posttransplant fatal complications and played a crucial role in determining the
      dog survival.

PMID- 12523812
TI  - A reappraisal of the ovine corticotropin-releasing hormone stimulation test in
      the differential diagnosis of Cushing's syndrome: a comparison with the standard
      high-dose dexamethasone suppression test.
AB  - BACKGROUND: We evaluated the diagnostic efficacy of the ovine corticotropin
      releasing hormone (oCRH) stimulation test in the differential diagnosis of
      Cushing's syndrome and compared it with the standard high-dose dexamethasone
      suppression test. METHODS: Twelve healthy volunteers and 30 with Cushing's
      syndrome (12 Cushing's disease and 18 adrenal Cushing's syndrome) were enrolled.
      Plasma ACTH and cortisol levels were measured before and after an intravenous
      bolus of 100 microg oCRH. Plasma and urinary free cortisol were determined after
      standard 2-day high-dose dexamethasone suppression. RESULTS: Basal cortisol in 12
      patients with Cushing's disease and 18 with adrenal Cushing's syndrome were
      higher than the control group (21.4 +/- 0.1 microg/dl vs. 22.3 +/- 0.5 microg/dl
      vs. 9.1 +/- 1.5 microg/dl; p < 0.01). In Cushing's disease, basal plasma ACTH
      value was significantly higher than those with adrenal disease (61.1 +/- 1.4
      pg/ml vs. 6.2 +/- 4.5 pg/ml; p < 0.01). After oCRH, plasma ACTH and cortisol
      significantly increased, with a mean of 2.0 +/- 0.2-fold (range 1.0-2.4) and 1.6
      +/- 0.1-fold (range 1.1-2.1), respectively over the basal values in patients with
      Cushing's disease, and 11 (90%) attained a significant ACTH (1.5-fold) or
      cortisol (1.2-fold) response. All except 2 (89%) with adrenal Cushing's showed no
      apparent change in response to oCRH. Dexamethsone suppressed urinary free
      cortisol by 90% in 8 (67%) with Cushing's disease, but all (100%) with adrenal
      Cushing's syndrome were resistant. No patient with Cushing's disease was
      refractory to oCRH and dexamethasone, while none with adrenal Cushing's syndrome
      was responsive to both. Combination of both tests could achieved a specificity of
      100% for Cushing's disease and adrenal Cushing's, when these 2 tests gave
      concomitant positive or negative results, respectively. CONCLUSIONS: The oCRH
      test is a reliable examination in the differential diagnosis of Cushing's
      syndrome and is comparable to the high-dose dexamethasone test. A highest
      discrimination could be achieved when both are used.

PMID- 12523815
TI  - Collagenous spherulosis presenting as a mass of the breast.
AB  - Collagenous spherulosis (CS) is a rare benign lesion which typically presents as
      an incidental microscopic finding accompanying other breast lesions. Pathologists
      who are not familiar with this entity occasionally misdiagnose CS as adenoid
      cystic carcinoma (ACC), cribriform ductal carcinoma in situ (C-DCIS), or atypical
      intraductal hyperplasia (AIH), especially when it presents as a mass. It is of
      utmost importance to differentiate benign CS from its malignant mimics in order
      to avoid unnecessary treatment. We report an unusual case of CS manifested as a
      mass in the right breast of a 45-year-old female and discuss the problems of
      differential diagnosis and histogenesis.

PMID- 12523814
TI  - Thyrotropin-secreting pituitary adenoma with growth hormone hypersecretion.
AB  - A 34-year-old woman suffered from palpitation, easy sweating, heat intolerance,
      increased appetite, irregular menstrual cycle and hand tremor for 1 year. Thyroid
      function tests showed elevated serum thyroxine (T4), tri-iodothyronine (T3) and
      thyrotropin (TSH). Computerized tomography (CT) revealed pituitary tumor with
      supraseller extension. Thyrotropin releasing hormone (TRH) test showed blunted
      TSH response with elevated baseline level and paradoxical growth hormone (GH)
      response with elevated baseline level. T3 suppression test (T3 60 microg per day
      x 10 days) showed no inhibition of TSH (11.1 microU/mL, normal range < 6.2
      microU/mL). She received transphenoidal approach and removal of tumor which
      measured 0.5 x 0.3 x 0.2 cm. Histopathologically, it was a pituitary adenoma
      which was immunoreactive for TSH, GH, follicular stimulating hormone (FSH) and
      luteinizing hormone (LH). To our knowledge, this case is the first case of TSH
      secreting pituitary adenoma in Taiwan.

PMID- 12523816
TI  - Phthiriasis palpebrarum: an unusual blepharoconjunctivitis.
AB  - Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may
      easily be overlooked because of the failure of physicians to recognize Phthirus
      pubis. We report a case of a 30-year-old woman with persistent itching in the
      left eyelid which was unsuccessfully treated under the diagnosis of allergic
      blepharoconjunctivitis. Careful ophthalmic examination revealed seven bugs with
      multiple red pinpoint excretions and numerous small translucent oval eggs (nits)
      coating the eyelashes. The patient was successfully treated with mechanical
      removal of all the lice and nits from the eyelashes. The specimen proved
      histopathologically to be the Phthirus pubis infestation. The Phthirus pubis
      infestation is usually associated with poor hygiene in overcrowded or undeveloped
      country. However, it may become a notable problem because of frequent traveling
      and commercial activities across the different countries.

PMID- 12523817
TI  - CJ-15,208, a novel kappa opioid receptor antagonist from a fungus, Ctenomyces
      serratus ATCC15502.
AB  - A novel kappa opioid receptor binding inhibitor CJ-15,208 (I) was isolated from
      the fermentation broth of a fungus, Ctenomyces serratus ATCC15502. The structure
      of I was determined to be a cyclic tetrapeptide consisting of one tryptophan, one
      D-proline, and two L-phenylalanine. Compound I was a selective binding inhibitor
      for the kappa opioid receptor: 47 nM (IC50) for kappa, 260 nM for mu, and 2,600
      nM for delta. In the electrically-stimulated twitch response assay of rabbit vas
      deferens I recovered the suppression by a kappa agonist asimadoline with an ED50
      of 1.3 microM, indicating that it is a kappa antagonist.

PMID- 12523818
TI  - GEX1 compounds, novel antitumor antibiotics related to herboxidiene, produced by
      Streptomyces sp. I. Taxonomy, production, isolation, physicochemical properties
      and biological activities.
AB  - Six structurally related antitumor antibiotics named GEX1 compounds were isolated
      from a culture broth of Streptomyces sp. GEX1A was identified as a known
      herbicide, herboxidiene, structurally interested by the tetrahydropyran moiety
      and the side chain including a conjugated diene. GEX1Q1 to approximately Q5 were
      determined as novel compounds related to herboxidiene. All GEX1 compounds showed
      cytotoxicity with IC50 values of 0.0037 to approximately 0.99 microM against
      human tumor cell lines in vitro, but were not active against both gram-positive
      and -negative bacteria. Though GEX1A/herboxidiene exhibited antitumor activity in
      murine tumor-planted mouse models, both GEX1Q3 and GEX1Q5 did not.

PMID- 12523819
TI  - GEX1 compounds, novel antitumor antibiotics related to herboxidiene, produced by
      Streptomyces sp. II. The effects on cell cycle progression and gene expression.
AB  - Six GEX1 compounds, GEX1A/herboxidiene and its related 5 novel compounds, were
      isolated from a culture broth of Streptomyces sp. GEX1 compounds induced both G1
      and G2/M arrest in a human normal fibroblast cell line, WI-38. All six compounds
      up-regulated luciferase reporter gene expression directed by enhancer/promoter of
      various genes, such as cdc2, IL-2 and SV40 early genes. All GEX1 compounds showed
      cytotoxic activities in the same order of the up-regulating activities on gene
      expression, suggesting that these two activities are related. Despite the up
      regulating activities on the reporter gene expression, GEX1A/herboxidiene did not
      enhance the expression of any endogenous genes involved in the cell cycle,
      proliferation and apoptosis. Although the unique effects of GEX1 compounds on
      cell cycle and the reporter gene expression were similar to those of trichostatin
      A (TSA), an inhibitor of histone deacetylase (HDAC), GEX1A/herboxidiene did not
      affect histone acetylation in cells. In addition, GEX1A/herboxidiene treatment
      gave rise to the shorter sized transcripts of the cdc25A and cdc2 genes as well
      as the normal sized ones. These results suggest that GEX1 compounds modulate gene
      expression by an unknown mechanism.

PMID- 12523820
TI  - TPU-0037-A, B, C and D, novel lydicamycin congeners with anti-MRSA activity from
      Streptomyces platensis TP-A0598.
AB  - In screening for anti-MRSA antibiotics, novel lydicamycin congeners, TPU-0037-A,
      B, C and D, were isolated from a culture broth of an actinomycete strain. The
      producing strain, TP-A0598, was isolated from a seawater sample collected in
      Toyama Bay, Japan, and identified as Streptomyces platensis based on taxonomic
      characteristics. TPU-0037-A, B, C and D were purified by HP-20 resin, ODS column
      chromatographies and preparative HPLC, consecutively, and their structures were
      determined to be 30-demethyllydicamycin, 14,15-dehydro-8-deoxylydicamycin, 30
      demethyl-8-deoxylydicamycin and 8-deoxylydicamycin, respectively, by NMR and MS
      analyses. The new congeners showed antibiotic activity against gram-positive
      bacteria including MRSA with the MIC of 1.56 to approximately 12.5 microg/ml.

PMID- 12523821
TI  - Altersetin, a new antibiotic from cultures of endophytic Alternaria spp.
      Taxonomy, fermentation, isolation, structure elucidation and biological
      activities.
AB  - A novel antibacterial antibiotic, for which the name altersetin is proposed, was
      isolated from the culture broth of two endophytic Alternaria species. The
      relative and absolute configuration were assigned by NOESY or CD data,
      respectively. Altersetin is chemically related to equisetin and showed potent MIC
      against several pathogenic gram-positive bacteria, whereas gram-negative bacteria
      and pathogenic yeast were not or much less susceptible. Moderate in vivo
      efficiacy was observed for altersetin in a murine sepsis model.

PMID- 12523822
TI  - Chalcomycin B, a new macrolide antibiotic from the marine isolate Streptomyces
      sp. B7064.
AB  - In our screening of marine streptomycete isolates for bioactive components, a new
      macrolide antibiotic designated as chalcomycin B (1b) was isolated from the
      culture broth of a marine Streptomycete isolate B7064 together with chalcomycin
      (1a) as the active principles. The structure of the new antibiotic was determined
      by EI and ESI MS, 1H, 13C and 2D NMR spectroscopy and by comparison of the NMR
      data with those of chalcomycin.

PMID- 12523823
TI  - Strain diversity within a microbial collection.
AB  - Random subsets of a modest-sized microbial collection have been examined for
      culture redundancy, initially by morphology, both to the naked eye and
      microscopically, of cultures grown on a variety of agar-based solid media.
      Subsequent analysis, by simple TLC, of the extractable metabolites produced by
      morphologically similar cultures grown in submerged shaken fermentation was
      carried out. Apparent duplicate cultures were further examined on Biolog SF-P
      MicroPlates for differentiation. The results were subjected to a statistical
      analysis and the contribution of each stage in the process to resolving culture
      uniqueness was noted. A statistical extrapolation of the results, from the
      subsets of each culture type, to the total for that type within the entire
      collection, with 95% confidence limits, is presented. Morphological comparison,
      on four different agar media, gives a significant underestimation of the
      metabolic diversity of the collection. The weighted mean from the three types of
      cultures indicate that the expected content of the collection is approximately
      93% unique strains.

PMID- 12523824
TI  - Reveromycin A inhibits antigen receptor-mediated antigen presentation by B
      lymphoma cells via its effect on intracellular trafficking of the antigen.
AB  - Reveromycin A (Rev.A) is an inhibitor of epidermal growth factor-dependent cell
      growth that is produced from the culture broth of an actinomycete strain. Rev.A
      was assessed for its ability to regulate antigen (Ag) presentation by A20-HL B
      lymphoma cells bearing trinitrophenyl (TNP)-specific surface IgM (sIgM) to cloned
      T cells specific for OVA(323-339)/I-Ad. Rev.A-treatment inhibited the
      presentation of Ag internalized via sIgM, but not of Ag via fluid-phase
      pinocytosis. Rev.A-treatment decreased protein synthesis, but a similar decrease
      in protein synthesis by cycloheximide induced much less inhibition of sIgM
      mediated Ag presentation. Rev.A-treatment decreased the rate of re-expression of
      sIgM in A20-HL cells, the amount of Ag internalized via sIgM during 3 hours of
      incubation, and the generation of antigenic peptides from TNP-OVA internalized
      via sIgM. Rev.A-treatment was suggested to affect intracellular trafficking from
      early endosomes into late endocytic compartments of Ag internalized via sIgM.
      Rev.A might provide a useful tool for studying intracellular transport of Ag,
      especially Ag internalized via sIgM.

PMID- 12523825
TI  - Isolation and structure elucidation of two new antibacterial compounds produced
      by Chrysosporium queenslandicum.

PMID- 12523826
TI  - Detection of the mevalonate pathway in Streptomyces species using the 3-hydroxy-3
      methylglutaryl coenzyme A reductase gene.

PMID- 12523827
TI  - Studies on bottromycins. II. Structure elucidation of bottromycins B2 and C2.

PMID- 12523828
TI  - A simple and effective method for producing nonrandom peptide libraries using
      cotton as a carrier in continuous flow peptide synthesizers.
AB  - A method has been developed for generating nonrandom peptide libraries on cotton.
      Disks of cotton fabric were chemically modified to enable peptide synthesis.
      Incorporation of a 6-aminocaproic acid residue handle on the cellulose turned out
      to be advantageous. Disks were labeled with silver ink, stacked one on top of
      another in a continuous flow peptide synthesizer column, and simultaneously
      subjected to automated synthesis procedures. Depending on the sequences to be
      synthesized, the automatic synthesis procedure was stopped, and the disks were
      removed from the column, sorted, and reapplied to subsequent synthesis steps. In
      this way, individual peptides could be easily prepared in milligram quantities on
      each of the cotton disks.

PMID- 12523829
TI  - Fluorescence spectroscopy and multivariate spectral descriptor analysis for high
      throughput multiparameter optimization of polymerization conditions of
      combinatorial 96-microreactor arrays.
AB  - Selection of optimum process conditions in combinatorial microreactors is
      essential if the combinatorial synthesis process is to be correlated with the
      synthesis process on a more conventional scale and the materials are to have the
      desired chemical properties. We have developed a new methodology for the high
      throughput multiparameter optimization of polymerization reaction conditions in
      arrays of microreactors. Our strategy is based on the application of
      nondestructive spectroscopic techniques to measure chemical properties of
      polymers directly in individual microreactors followed by the multivariate
      spectral descriptor analysis for rapid determination of the optimal process
      conditions. We have demonstrated our strategy in the high-throughput
      multiparameter optimization of process conditions in thin-film melt
      polymerization reactions performed in 96-microreactor arrays for combinatorial
      screening of new polymerization catalysts. The combinatorial polymerization
      system was optimized for the best processing parameters using a set of input
      variables that included reactant parameters (relative amounts of starting
      components and catalyst loading) and processing variables (reaction time,
      reaction temperature, and inert gas flow rate). The measured output parameters
      were the chemical properties of materials and reproducibility of the material
      formation in replicate polymerizations in microreactors. Spatially resolved
      nondestructive evaluation of polymer formation was performed directly in
      individual microreactors and provided information about the spatial homogeneity
      of polymers in microreactors. It showed to be another powerful indicator of the
      reproducible polymerization process on the combinatorial scale. Although the
      methodology described here was implemented for high-throughput optimization of
      polymerization conditions, it is more general and can be further implemented for
      a variety of applications in which optimization of process parameters can be
      studied in situ or off-line using spectroscopic and other tools.

PMID- 12523830
TI  - Glycopeptides as oligosaccharide mimics: high affinity sialopeptide ligands for
      sialoadhesin from combinatorial libraries.
AB  - Two different sialic acid containing glycopeptide (sialopeptide) libraries were
      synthesized using the portion mixing method and ladder synthesis. The libraries
      were attached via an IMP spacer and a photolabile linker to PEGA(1900) resin in
      order to facilitate rapid and unambiguous structural analysis of hits by MALDI
      TOFMS. One library contained a lactamized sialic acid moiety at the N terminus of
      a pentapeptide, while a second library displayed a sialic acid residue at the
      center of a heptapeptide. The sialopeptide libraries were screened against the
      recombinant binding domain (SnD1) of a sialic acid binding Ig-like protein,
      sialoadhesin (Siglec-1). No ligands were identified from the lactamized sialic
      acid library, underscoring the importance of the carboxylic acid moiety for
      binding. Screening of the second gave few distinct hits (approximately 0.03% of
      library) with a high consensus. The high-affinity ligands contained, in most
      cases, a WG motif following the sialylated Thr. The strength of binding of
      selected ligands was determined by surface plasmon resonance. The best
      sialopeptide ligand, WLLT(Sa)WGT, exhibited micromolar affinity of SnD1; >10
      times the affinity of SnD1 to 3'-sialyl lactose.

PMID- 12523831
TI  - Which sites react first? Functional site distribution and kinetics on solid
      supports investigated using confocal Raman and fluorescence microscopy.
AB  - Fluorescence microscopy is a powerful technique for analyzing beads with very low
      loadings of fluorophores; however, the method is flawed when looking at more
      highly loaded beads as a result of severe problems with absorption. To probe
      distributions at higher loading levels, Raman spectroscopy avoids many of these
      issues. These studies show that there is a uniform distribution of reactive sites
      throughout the beads but that the spatial distribution of reacted sites depends
      on the polymer type, with a fine balance between reaction and diffusion rate.

PMID- 12523833
TI  - A facile solution phase combinatorial synthesis of tetrasubstituted pyridines
      using the Bohlmann-Rahtz heteroannulation reaction.
AB  - The solution phase combinatorial Bohlmann-Rahtz reaction gives highly
      functionalized pyridine libraries from enamino esters and alkynones in a single
      synthetic step. Good product ratios and library purities were obtained in
      reactions catalyzed by zinc(II) bromide, the acid-catalyzed heteroannulation
      procedure offering considerable improvements over traditional methodology.

PMID- 12523832
TI  - Automated mass spectrometric sequence determination of cyclic peptide library
      members.
AB  - Cyclic peptides have come under scrutiny as potential antimicrobial therapeutic
      agents. Combinatorial split-and-pool synthesis of cyclic peptides can afford
      single compound per well libraries for antimicrobial screening, new lead
      identification, and construction of quantitative structure-activity relationships
      (QSAR). Here, we report a new sequencing protocol for rapid identification of the
      members of a cyclic peptide library based on automated computer analysis of mass
      spectra, obviating the need for library encoding/decoding strategies.
      Furthermore, the software readily integrates with common spreadsheet and database
      packages to facilitate data visualization and archiving. The utility of the new
      MS-sequencing approach is demonstrated using sonic spray ionization ion trap MS
      and MS/MS spectrometry on a single compound per bead cyclic peptide library and
      validated with individually synthesized pure cyclic D,L-alpha-peptides.

PMID- 12523834
TI  - Rapidly measuring reactivities of carboxylic acids to generate equireactive
      building block mixtures: a spectrometric assay.
AB  - The relative reactivity of building blocks is critical for a successful
      preparation of combinatorial libraries. Here, we present a method for measuring
      the reactivity of carboxylic acid building blocks in amide-forming reactions. The
      method involves competitive reactions between a reference and test acid and a
      tetraphenylporphyrin reaction partner with four reactive sites. Relative
      reactivities are calculated on the basis of the distribution of substituted
      porphyrins found in MALDI-TOF mass spectra. Reactivities thus determined were
      used to prepare reactivity-adjusted building block mixtures. These were reacted
      with amino-terminal oligonucleotide and peptide scaffolds on solid support,
      generating small libraries suitable for spectrometrically monitored selection
      experiments (SMOSE). The rate of building block "drop outs" that fail to couple
      as expected was not substantially lowered by acquiring spectra from two
      reactions, performed with different ratios of building blocks, where the effect
      of a given substituent on the desorption/ionization yield of the porphyrin can be
      eliminated. Instead, coupling building blocks of similar size together or
      employing N-hydroxysuccinimide esters rather than activating with a "uronium
      salt" were found to improve the quality of libraries generated via competitive
      reactions.

PMID- 12523835
TI  - High-throughput purification of combinatorial arrays.
AB  - Performance and reproducibility of the Biotage Parallex, a high-throughput
      purification system, was evaluated using known standards. The results indicate
      that parallel purification is a robust technique for purifying large numbers of
      compounds. Results from one of the first libraries to be purified on the Biotage
      Parallex are presented and discussed. Since fractionation by UV can often result
      in a large number of fractions, threshold trigger versus yield and number of
      fractions was also investigated. This approach was used to purify an array of
      4320 compounds, produced by an 11-step solid-phase synthesis in Irori MicroKans.
      Ninety-three percent of the compounds were successfully processed, with >90%
      having purity >95%.

PMID- 12523836
TI  - Synthesis and screening of a molecularly imprinted polymer library targeted for
      penicillin G.
AB  - A library of molecularly imprinted polymers (MIPs) was synthesized by radical
      bulk polymerization using the beta-lactam antibiotic penicillin G as the
      template. Diversity of the library was obtained by combining various
      functionalized monomers and cross-linkers and by varying the stoichiometry and
      the concentration of the components in the prepolymerization mixtures. The
      library was screened for selectivity to penicillin G by a radioligand binding
      assay and was compared to a corresponding control library. The best MIP
      candidate, showing the highest selectivity for penicillin G, was prepared from
      methacrylic acid and trimethylolpropane trimethacrylate as the functionalized
      monomer and cross-linker, respectively. Cross-reactivity studies with other beta
      lactam antibiotics showed a low cross-reactivity of penicillin V (15%),
      ampicillin (16%), and amoxicillin (19%). Nafcillin and oxacillin showed less
      cross-reactivity (<1%). Cross-reaction with a cephalosporin antibiotic
      (cephapirin) and structurally nonrelated antibiotics (chloramphenicol,
      tetracycline, dapsone, and erythromycin) was less than 0.01%.

PMID- 12523837
TI  - Efficient synthesis of 2,4-disubstituted 1,2,4-benzothiadiazin-3-one 1,1-dioxides
      on solid support.
AB  - The first solid-phase synthesis of 1,2,4-benzothiadiazin-3-one 1,1-dioxides has
      been developed. Synthesis of the title compounds was achieved by the reduction of
      2-nitrobenzenesulfonamides, followed by cyclization with carbonyldiimidazole.
      Because 1,2,4-benzothiadiazin-3-one 1,1-dioxides have been known to possess
      various bioactivities, this method is useful from the viewpoint of new drug
      discovery. In addition to the excellent purity of the title compounds, a large
      number of compounds can be synthesized with this method, because this synthesis
      includes four diversity points.

PMID- 12523838
TI  - General trend of lipase to self-assemble giving bimolecular aggregates greatly
      modifies the enzyme functionality.
AB  - Three microbial lipases (those from Candida rugosa, Humicola lanuginosa, and
      Mucor miehei) have been found to exhibit a tendency to form bimolecular
      aggregates in solution even at very low enzyme concentrations (44 microg/mL) in
      the absence of a detergent, as detected by gel filtration. The monomolecular form
      of the enzymes was found as unique only at low enzyme concentration and in the
      presence of detergents. However, in the case of the lipase B from Candida
      antarctica, no bimolecular form could be identified even at enzyme concentrations
      as high as 1.2 mg/mL in the absence of detergent. It has been stated that
      bimolecular and monomolecular structures display very different functional
      properties: (i) the enzyme specific activity decreased when the lipase
      concentration increased; (ii) the bimolecular form was much more stable than the
      monomeric one yielding a higher optimal T (increasing between 5 and 10 degrees C)
      and higher stability in inactivation experiments (the dimer half-life became
      several orders of magnitude higher than that of the monomer); (iii) the
      enantioselectivity depended on the enzyme concentration even after
      immobilization. For example, with use of the lipase from H. lanuginosa, the
      enantiomeric excess of the remaining ester in the hydrolysis of fully soluble
      ethyl ester of (R,S)-2-hydroxy-4-phenylbutanoic acid varied from 4 to 57 when the
      concentrated or diluted enzyme immobilized on PEI support, respectively, was
      used. It seems that the bimolecular structure of lipases might be formed by two
      open lipase molecules (interfacially activating each other) in very close contact
      and hence with a very altered active center.

PMID- 12523839
TI  - In vitro hydrolysis of blends from enantiomeric poly(lactide)s. 3.
      Homocrystallized and amorphous blend films.
AB  - Homocrystallized and amorphous enantiomeric blend films were prepared from the
      melt of high molecular weight poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA)
      (1:1) by crystallization and quenching, respectively. A phosphate-buffered
      solution was used to investigate effects of homocrystallinity via in vitro
      hydrolysis as well as crystallization process during the hydrolysis, which was
      performed for a period of 24 months at 37 degrees C and pH 7.4. Results derived
      from gravimetry, gel permeation chromatography, and tensile testing showed that
      hydrolyzability was higher for the homocrystallized film than for the amorphous
      film. Thus, probable mechanisms are proposed for the enhanced hydrolysis of the
      homocrystallized blend film compared with that of the amorphous blend film. The
      hydrolysis rate constant (k) values of the homocrystallized and amorphous films
      estimated from the changes in number-average molecular weight (M(n)) were 5.00 x
      10(-3) and 3.32 x 10(-3) day(-1), respectively. Moreover, hydrolyzability of
      equimolar enantiomeric poly(lactic acid) blends can be altered in the k range of
      0.73 x 10(-3) and 5.00 x 10(-3) day(-1) by varying their crystalline species,
      crystallinity, or molecular weights.

PMID- 12523840
TI  - Optimization of chitin extraction from shrimp shells.
AB  - The aim of this paper is to define optimal conditions for the extraction of
      chitin from shrimp shells. The kinetics of both demineralization and
      deproteinization with, in the latter case, the role of temperature are studied.
      The characterization of the residual calcium and protein contents, the molecular
      weights, and degrees of acetylation (DA) allows us to propose the optimal
      conditions as follows. The demineralization is completely achieved within 15 min
      at ambient temperature in an excess of HCl 0.25 M (with a solid-to-liquid ratio
      of about 1/40 (w/v)). The deproteinization is conveniently obtained in NaOH 1 M
      within 24 h at a temperature close to 70 degrees C with no incidence on the
      molecular weight or the DA. In these conditions, the residual content of calcium
      in chitin is below 0.01%, and the DA is almost 95%.

PMID- 12523841
TI  - Polymerization of propyl malolactonate in the presence of Candida rugosa lipase.
AB  - To gain better insight into mechanistic features of enzyme-catalyzed
      malolactonate polymerization, reactions with propyl malolactonate were analyzed
      while varying enzyme concentration, reaction media composition, and reaction
      temperature. Monomer conversion and product molecular weights were characterized
      by (1)H NMR and MALDI-TOF MS, respectively. A high extent of thermal
      polymerization of propyl malolactonate was observed, while the polymer chain
      length in all reactions was controlled by the elimination of alpha-hydrogen from
      propyl malolactonate with formation of a new initiator and the new chains. The
      most efficient enzymatic catalysis occurred in toluene (2.11 M monomer) at 60
      degrees C. Candida rugosa lipase (10 wt %) accelerated polymerization 25-fold
      over the rate of thermal polymerization. The maximum poly(propyl malate) number
      average molecular weight obtained was 5000 Da at 20 wt % enzyme with a
      polydispersity of 1.15. These values compare with 1800 Da and 1.5, respectively,
      in the absence of enzyme.

PMID- 12523842
TI  - On the long-range attraction between proteins due to nonadsorbing polysaccharide.
AB  - The effect of a nonadsorbing polysaccharide (dextran) on the structure factor of
      a solution of lysozyme was studied using small-angle neutron scattering (SANS)
      experiments. By choosing the appropriate water/deuterium ratio as solvent, we
      made the scattering signal from dextran invisible for the SANS measurements.
      Dextran induces a weak long-range attraction between the lysozyme molecules. This
      attraction is described using a depletion interaction potential from theory for
      two spheres in an ideal polymer solution. Incorporation of the theory in a mean
      spherical approximation shows that the wave vector below which the structure
      factor increases depends on the polymer size. The theoretical prediction is in
      fair agreement with the measured structure factor of lysozyme, as affected by
      nonadsorbing dextran.

PMID- 12523843
TI  - Interaction of double-stranded T4 DNA with cationic gel of
      poly(diallyldimethylammonium chloride).
AB  - Interaction between duplex T4 DNA and a slightly cross-linked cationic gel of
      poly(diallyldimethylammonium chloride) in aqueous media was studied by
      fluorescent microscopy. While short DNA chains such as plasmid DNAs penetrate
      into the gel and form a phase of polyelectrolyte complex with the cationic
      network, the genomic giant DNA chains of T4 phages form complexes only on local
      areas of the gel surface. The DNA/gel complex exhibited different characteristic
      morphologies depending on the conditions for preparing the complex, such as the
      DNA concentration, flux of the solution, and surface geometry of the gel: (1) In
      the interaction with the flat surface of film-type gel, compact round objects,
      which reflected a condensed state of single DNA chains, were observed. (2) In the
      interaction with partly dried gel, a characteristic pattern similar to
      propagating waves was formed on the gel surface. (3) When flux is generated for a
      concentrated DNA solution, long oriented fiberlike structures were formed, which
      consisted of ensembles of chains. The interaction with small pieces of
      mechanically decomposed gel leads to complete covering of their surface by the
      DNA.

PMID- 12523844
TI  - Biosynthesis and local sequence specific degradation of poly(3-hydroxyvalerate-co
      4-hydroxybutyrate) in Hydrogenophaga pseudoflava.
AB  - A novel copolymer that consisted of 3-hydroxyvalerate and 4-hydroxybutyrate,
      P(3HV-co-4HB), was synthesized in Hydrogenophaga pseudoflava by growing it in
      media containing gamma-valerolactone and gamma-butyrolactone as a carbon source.
      The monomer ratio in the copolymer was changed by altering the feed ratio of the
      two lactones. The cultivation technique was composed of three steps: the first
      step for high cell production in Luria-Bertani medium, the second-step for
      intracellular degrading removal of poly(3-hydroxybutyrate) (P(3HB)), which was
      formed in the first step, by culturing the cells in carbon-source-free medium,
      and the final step for accumulation of P(3HV-co-4HB) in a mixed lactone medium.
      All the P(3HV-co-4HB) copolymers contained less than 1 mol % of 3HB unit. These
      copolymers were characterized by NMR spectroscopy, differential scanning
      calorimetry, wide-angle X-ray diffraction, and first-order kinetic analysis of
      intracellular degradation. The copolymer with an approximately equal ratio of the
      comonomers was found amorphous. The NMR microstructural analysis showed that the
      copolymers contained appreciable amounts of 3HV-rich or 4HB-rich chains. The
      (13)C NMR splitting patterns associated with the four carbons in the 4HB unit of
      P(3HV-co-4HB) bear close resemblance to those observed in the 4HB unit of P(3HB
      co-4HB). The signals arising from the carbons in the 3HV unit of P(3HV-co-4HB)
      split in a manner similar to those in the 3HB unit of P(3HB-co-4HB). Thus the
      sequences were assigned by comparing the NMR splittings for P(3HV-co-4HB) with
      those for P(3HB-co-4HB) and P(3HB-co-3HV). The sequence assignment was further
      checked by comparing the signal intensities before and after degradation of the
      copolymers. This was considered reasonable because the H. pseudoflava
      intracellular PHA depolymerase is more specific to the 3HV unit than to the 4HB
      unit, which was also confirmed by the higher degradation rate constant for the
      3HV unit in the first-order kinetic analysis.

PMID- 12523845
TI  - Characterization of biodegradation intermediates of nonionic surfactants by MALDI
      MS. 2. Oxidative biodegradation profiles of uniform octylphenol polyethoxylate in
      18O-labeled water.
AB  - This paper reports the characterization of the biodegradation intermediates of
      octylphenol octaethoxylate (OP(8)EO) by means of matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS). The biodegradation test study
      was carried out in a pure culture (Pseudomonas putida S-5) under aerobic
      conditions using OP(8)EO as the sole carbon source and (18)O-labeled water as an
      incubation medium. In the MALDI-MS spectra of biodegraded samples, a series of
      OP(n)EO molecules with n = 2-8 EO units and their corresponding carboxylic acid
      products (OP(n)EC) were observed. The use of purified OP(8)EO enabled one to
      distinguish the shortened OPEO molecules as biodegradation intermediates.
      Furthermore, the formation of OP(8)EC (the oxidized product of OP(8)EO) supported
      the notion that terminal oxidation is a step in the biodegradation process. When
      biodegradation study was carried out in (18)O-labeled water, incorporation of
      (18)O atoms into the carboxyl group was observed for OPEC, while no incorporation
      was observed for the shortened OPEO products. These results could provide some
      rationale to the biodegradation mechanism of alkylphenol polyethoxylates.

PMID- 12523846
TI  - Release of phospholipids from colloidal particles to polymeric surfaces.
AB  - This study presents a small-scale polymerization of high molecular weight methyl
      methacrylate/n-butyl acrylate (MMA/n-BA) colloidal particles that are synthesized
      in an aqueous environment in the presence of phospholipid hydrogenated soybean
      phosphatidylcholine (HSPC) molecules that also serve as the particle stabilizing
      agents. When such particles coalesce to form polymeric films, they release
      phospholipids, which, in turn, form organized structures near the film-air (F-A)
      interface. Diffusion and mobility of phospholipid molecules are affected not only
      by their compatibility with colloidal particles but also by electrolyte
      environments of colloidal dispersions. When Na(+), K(+), and Ca(2+) counterions
      are added to MMA/n-BA aqueous colloidal dispersions stabilized with HSPC, and
      such films are coalesced, different degrees of diffusion of HSPC to the F-A
      interface exist, depending on the counterion, and conformational changes of HSPC
      result. For example, in the presence of Ca(2+), HSPC molecules collapse
      entropically to form random surface layers, as opposed to smaller Na(+) and K(+),
      which force amphiphilic HSPC ends to align preferentially parallel to the film
      surface. These studies show that it is possible to design stimuli-response
      colloidal systems triggered by chemical environments of active molecules on
      colloidal polymer particles.

PMID- 12523848
TI  - Oxidative quenching of spruce thermomechanical pulp fiber autofluorescence
      monitored in real time by confocal laser scanning microscopy-implications for
      lignin autofluorescence.
AB  - Confocal laser scanning microscopy (CLSM) was used to monitor real-time lignin
      autofluorescence intensities from different cell wall compartments of spruce
      fibers during oxidation by laccase-2,2'-azinobis-3-ethylbenzthiazoline-6
      sulfonate (ABTS) treatment. CLSM data revealed an instant emission quenching from
      all cell wall compartments, including those not physically accessible to enzyme
      or ABTS, followed by an additional decrease simultaneously in all cell wall
      compartments over a 45 min time course. The importance of site-to-site excitation
      energy transfer in lignin efficient over long distance is suggested.

PMID- 12523847
TI  - Enhanced bone marrow stromal cell adhesion and growth on segmented poly(ether
      ester)s based on poly(ethylene oxide) and poly(butylene terephthalate).
AB  - In previous studies in rats and goats, hydrophilic compositions of the PEOT/PBT
      block copolymer family have shown in vivo calcification and bone bonding. These
      copolymers are therefore interesting candidates as scaffolding materials in bone
      tissue engineering applications. Model studies using goat bone marrow stromal
      cells, however, showed that it was not possible to culture bone marrow stromal
      cells in vitro on these hydrophilic copolymers. In this paper two ways of surface
      modifying these materials to improve in vitro bone marrow stromal cell attachment
      and growth are discussed. Two different approaches are described: (1) blending of
      hydroxyapatite (HA) followed by CO(2) gas plasma etching; (2) surface
      modification using CO(2) gas plasma treatments. It was observed that not only HA
      but also the CO(2) plasma treatment by itself has a positive effect on bone
      marrow stromal cell attachment and growth. Gas plasma treatment appeared to be
      the most successful approach, resulting in a large increase in the amount of bone
      marrow stromal cells present on the surface (determined by a DNA assay). The
      amount of DNA present on the plasma-treated copolymer 1000/70/30 PEOT/PBT, based
      on poly(ethylene oxide, M(w) = 1000, 70 m% soft segment), was comparable to the
      amount present on PDLLA and significantly higher than the amount present on PCL
      after 7 days of cell culturing. The fact that after gas plasma treatment bone
      marrow stromal cells do attach to PEOT/PBT copolymers, enables in vitro bone
      marrow stromal cell culturing, making bone tissue engineering applications of
      these materials possible.

PMID- 12523849
TI  - Imaging the distribution and secondary structure of immobilized enzymes using
      infrared microspectroscopy.
AB  - Synchrotron infrared microspectroscopy (SIRMS) was used for the first time to
      image the distribution and secondary structure of an enzyme (lipase B from
      Candida antarctica, CALB) immobilized within a macroporous polymer matrix
      (poly(methyl methacrylate)) at 10 microm resolution. The beads of this catalyst
      (Novozyme435) were cut into thin sections (12 microm). SIRMS imaging of these
      thin sections revealed that the enzyme is localized in an external shell of the
      bead with a thickness of 80-100 microm. Also, the enzyme was unevenly distributed
      throughout this shell. Furthermore, by SIRMS-generated spectra, it was found that
      CALB secondary structure was not altered by immobilization. Unlike CALB,
      polystyrene molecules of similar molecular weight diffuse easily throughout
      Novozyme435 beads. Scanning electron micrograph (SEM) images of the Novozyme435
      beads showed that the average pore size is 10 times larger than CALB or
      polystyrene molecules, implying that there is no physical barrier to enzyme or
      substrate diffusion throughout the bead. Thus, the difference between polystyrene
      and enzyme diffusivity suggests that protein-matrix and protein-protein
      interactions govern the distribution of the enzyme within the macroporous resin.

PMID- 12523850
TI  - Synthesis, characterization, and preliminary biological study of poly(3-(tert
      butoxycarbonyl)-N-vinyl-2-pyrrolidone).
AB  - Poly(3-(tert-butoxycarbonyl)-N-vinyl-2-pyrrolidone) has been synthesized and
      characterized by gel permeation chromatography, Fourier transform infrared
      spectroscopy, NMR spectroscopy, and thermal analysis. The polymer is a chemically
      amplified photoresist. Arrays of lines with 25 microm width and 25 microm spacing
      were successfully patterned with this polymer by photolithography. Rat fibroblast
      cells were seeded on these patterned surfaces as well as the smooth glass
      surface. Phase contrast microscopy showed that cells on the patterned surfaces
      were strongly aligned and elongated along the grooves as compared to randomly
      spreading on the smooth surface. Since controlling cell orientation is critical
      for the development of advanced forms of tissue repair and cell engineering
      therapies, for example, peripheral nerve repair, production of tendon and
      ligament substitutes in vitro, and control of microvascular repair, the described
      polymer may be useful for applications in tissue reconstruction.

PMID- 12523851
TI  - Genetic analysis and characterization of poly(aspartic acid) hydrolase-1 from
      Sphingomonas sp. KT-1.
AB  - Sphingomonas sp. KT-1 hydrolyzes poly(aspartic acid) (PAA) containing alpha- and
      beta-amide units and has at least two different types of PAA hydrolases. The PAA
      hydrolase-1 hydrolyzes selectively beta-beta amide units in PAA. Molecular
      cloning of PAA hydrolase-1 from Sphingomonas sp. KT-1 has been carried out to
      characterize its gene products. Genetic analysis shows that the deduced amino
      acid sequence of PAA hydrolase-1 has a similarity with those of the catalytic
      domain of poly(3-hydroxybutyric acid) (PHB) depolymerases from Alcaligenes
      faecalis AE122 and Pseudomonas lemoignei. Site-specific mutation analysis
      indicates that (176)Ser is a part of a strictly conserved pentapeptide sequence
      (Gly-Xaa-Ser-Xaa-Gly), which is the lipase box, and plays as an active residue.

PMID- 12523852
TI  - Comblike poly(alpha-alkyl gamma-glutamate)s: computer simulation studies of an
      intermediate thermal phase.
AB  - Monte Carlo (MC) simulations have been used to study the structure of an
      intermediate thermal phase of poly(alpha-octadecyl gamma,D-glutamate). This is a
      comblike poly(gamma-peptide) able to adopt a biphasic structure that has been
      described as a layered arrangement of backbone helical rods immersed in a
      paraffinic pool of polymethylene side chains. Simulations were performed at two
      different temperatures (348 and 363 K), both of them above the melting point of
      the paraffinic phase, using the configurational bias MC algorithm. Results
      indicate that layers are constituted by a side-by-side packing of 17/5 helices.
      The organization of the interlayer paraffinic region is described in atomistic
      terms by examining the torsional angles and the end-to-end distances for the
      octadecyl side chains. Comparison with previously reported comblike poly(beta
      peptide)s revealed significant differences in the organization of the alkyl side
      chains.

PMID- 12523854
TI  - One-step purification, covalent immobilization, and additional stabilization of a
      thermophilic poly-His-tagged beta-galactosidase from Thermus sp. strain T2 by
      using novel heterofunctional chelate-epoxy Sepabeads.
AB  - Using the poly-His-tagged-beta-galactosidase from Thermus sp. strain T2
      overexpressed in Escherichia coli (MC1116) as a model enzyme, we have developed a
      strategy to purify and immobilize proteins in a single step, combining the
      excellent properties of epoxy groups for enzyme immobilization with the good
      performance of immobilized metal-chelate affinity chromatography for protein
      purification. The aforementioned enzyme could not be immobilized onto standard
      epoxy supports with good yields, and after purification and storage, it exhibited
      a strong trend to yield very large aggregates as shown by ultracentrifugation
      experiments. That preparation could not be immobilized in any support, very
      likely because the pores of the solid became clogged by the large aggregates.
      These novel epoxy-metal chelate heterofunctional supports contain a low
      concentration of Co(2+) chelated in IDA groups and a high density of epoxy
      groups. This enabled the selective adsorption of poly-His-tagged enzymes, and as
      this adsorption step is necessary for the covalent immobilization procedure, the
      selective covalent immobilization of the target enzyme could take place. This
      strategy allowed similar maximum loadings of the target enzyme using either pure
      or crude preparations of the enzyme. The enzyme derivative presented a very high
      activity at 70 degrees C (over 1000 IU in the hydrolysis of lactose) and very
      high stability and stabilization when compared to its soluble counterpart
      (activity remained unaltered after several days of incubation at 50 degrees C).
      In fact, this preparation was much more stable than when the same enzyme was
      immobilized onto standard epoxy Sepabeads.

PMID- 12523853
TI  - Rational design of cytophilic and cytophobic polyelectrolyte multilayer thin
      films.
AB  - Nanostructured polyelectrolyte multilayer thin films electrostatically assembled
      alternately from such polymers as poly(allylamine hydrochloride) (PAH) and
      poly(acrylic acid) (PAA) were investigated for their in vitro cell interactions.
      Not surprisingly, NR6WT cells, a highly adhesive murine fibroblast cell line,
      attached to many different multilayer combinations tested. However, PAH/PAA
      multilayers constructed at pH deposition conditions of 2.0/2.0 were completely
      bioinert. Analogous cell interactions were observed with PAH/poly(methacrylic
      acid) (PAH/PMA), PAH/sulfonated poly(styrene) (PAH/SPS), and
      poly(diallyldimethylammonium chloride)/SPS (PDAC/SPS) systems, thereby suggesting
      a general trend in the fibroblasts' response to multilayers. Specifically, highly
      ionically stitched films attracted cells, whereas weakly ionically cross-linked
      multilayers, which swell substantially in physiological conditions to present
      richly hydrated surfaces, resisted fibroblast attachment. Thus, by manipulating
      the multilayer pH or ionic strength assembly conditions or both, which in turn
      dictate the molecular architecture of the thin films, one may powerfully direct a
      single multilayer combination to be either cell adhesive or cell resistant.

PMID- 12523855
TI  - Fluorescent chelates for monitoring metal binding with macromolecules.
AB  - Metals and radionuclides are usually coupled with proteins together with suitable
      ligands for therapeutic, tumor-imaging, pharmaceuticals, and biocompatibility
      applications. Several ligands that can strongly coordinate a given nuclide in a
      specific valency are already known. However, the demand for bifunctionality has
      limited the applications of these ligands. We hereby report the molecular design
      of a receptor system based on the linkage of protein to monoazo ligands. By use
      of basic coordination chemistry, 4-(3-quinolinoazo)hydroxybenzoic acid (QABA) and
      derivatives were successfully conjugated to ovalbumin, bovine serum albumin, and
      alkaline phosphatase at a site that was distinct from the metal binding site. The
      presence of carboxylic acid linkage in the QABA served as a convenient bridge for
      protein conjugation and may allow the generic application of these ligands for
      bioconjugate synthesis while ensuring a high in vivo stability. The ligand
      protein conjugates were characterized using UV-vis spectroscopy, Fourier
      transform infrared spectroscopy, thin layer chromatography, NMR, and surface
      enhanced laser desorption ionization time-of-flight mass spectrometry. The
      conjugate was tested for the ability to recognize nonradioactive Ga(3+) at a
      physiological pH, and a binding constant of 1 x 10(20) was recorded. Also, the in
      vitro testing results indicated that the fluorescent conjugates exhibited
      significant selectivity for gallium compared to Pb(2+), Hg(2+), Zn(2+), Cu(2+),
      Fe(3+), and Co(2+) while no responses were obtained for alkaline and alkaline
      earth metals. These attributes could allow these conjugates to be used as a model
      for imaging sensors and for metal detection.

PMID- 12523856
TI  - Noncovalent chiral domino effect on one-handed helix of nonapeptide containing a
      midpoint L-residue.
AB  - We here clarify whether noncovalent chiral domino effect characterized by the
      terminal interaction of a helical peptide with a chiral small molecule can alter
      the helical stability of N-deprotected peptides containing an L-residue
      covalently incorporated into the inner position. Two nonapeptides consisting of
      the midpoint L-leucine (1) or L-phenylalanine (2) and the achiral helix-forming
      residues were employed. NMR and IR spectroscopy and energy calculation indicated
      that both peptides adopt a 3(10)-helical conformation in chloroform. They
      strongly preferred a right-handed screw sense because of the presence of the
      midpoint L-residue. These original right-handed screw senses were retained on
      addition of chiral Boc-amino acid, but their helical stabilities clearly depended
      on its added chirality. Here, Boc-L-amino acid stabilizes the original right
      handed helix, whereas the corresponding Boc-D-amino acid tends to less stabilize
      or destabilize it. This tendency was not observed for the corresponding N-Boc
      protected peptides 1 and 2, strongly suggesting that the N-terminal amino group
      is required for controlling the stabilization of the original right-handed helix.
      Therefore, noncovalent chiral domino effect in peptides 1 and 2 can contribute
      even to the helical stability of a chiral peptide prevailing one-handed helix
      strongly through the midpoint L-residue. In addition, the N-terminal moiety of a
      3(10)-helical peptide was found to generate chiral discrimination in complexation
      process with racemic additives.

PMID- 12523857
TI  - Morphology and kinetics of phase separating transparent xanthan-colloid mixtures.
AB  - We present a study on the morphology and kinetics of depletion-induced phase
      separation in aqueous xanthan-colloid mixtures with light microscopy and small
      angle light scattering (SALS), using fluorinated colloids with a refractive index
      close to that of water to prevent complications of multiple scattering.
      Microscopy with the direction of observation perpendicular to gravity enabled us
      to observe the development of the microstructure during the entire phase
      separation process including the formation of a macroscopic interface.
      Bicontinuous structures typical of a spinodal decomposition mechanism were
      observed at early times. These structures coarsened in time until hydrodynamic
      flow resulted in lane formation. Close to the binodal, a nucleation-and-growth
      mechanism was observed with formation of droplets. The coarsening kinetics were
      studied in more detail with SALS and turbidity measurements. Above polysaccharide
      concentrations at which entanglements become dominant, a slower coarsening and
      macroscopic phase separation were found because of the high continuous phase
      viscosity.

PMID- 12523858
TI  - Dehydration from alcohols by polyion complex cross-linked chitosan composite
      membranes during evapomeation.
AB  - This study describes the dehydration of an ethanol/water azeotrope during
      evapomeation using polyion complex cross-linked chitosan composite (q-Chito-PEO
      acid polyion complex/PES composite) membranes, constructed from quaternized
      chitosan (q-Chito) and poly(ethylene oxydiglycolic acid) (PEO acid) on a porous
      poly(ether sulfone) (PES) support. Both the q-Chito/PES composite and the q-Chito
      PEO acid polyion complex/PES composite membranes showed high water
      permselectivity for an ethanol/water azeotrope. Both the permeation rate and the
      water permselectivity of the q-Chito/PES composite membranes were enhanced by
      increasing the degree of quaternization of the chitosan molecule because the
      affinity of the q-Chito/PES composite membranes for water was increased by
      introducing a quaternized ammonium group into the chitosan molecule. q-Chito-PEO
      acid polyion complex/PES composite membranes prepared from an equimolar ratio of
      carboxylate groups in the PEO acid versus quaternized ammonium groups in the q
      Chito showed the maximum separation factor for water permselectivity without
      lowering the permeation rate. With an increasing molecular weight of PEO acid,
      the separation factor for water permselectivity increased, but the permeation
      rate almost did not change. The mechanism responsible for the separation of an
      ethanol/water azeotrope through the q-Chito-PEO acid polyion complex/PES
      composite membranes was analyzed by the solution-diffusion model. The permeation
      rate, separation factor for water permselectivity, and evapomeation index of q
      Chito-PEO acid 400 polyion complex/PES composite membrane with an equimolar ratio
      of carboxylate groups in PEO acid 400 and ammonium groups in q-Chito were 3.5 x
      10(-1) kg/(m(2) hr), 6300, and 2205, respectively, and very high membrane
      performance. The separation factor for water permselectivity for aqueous
      solutions of n-propyl and isopropyl alcohol was also maximized at an equimolar
      ratio of carboxylate groups and ammonium groups and was greater than that for an
      ethanol/water azeotrope. The above results were discussed from the viewpoint of
      the physical and chemical structure of the q-Chito-PEO acid polyion complex/PES
      composite membranes and the permeants.

PMID- 12523859
TI  - Silicone elastomer surface functionalized with primary amines and subsequently
      coupled with heparin.
AB  - Primary amines covalently bonded to the surface of poly(dimethylsiloxane) were
      obtained by hydrosilylation grafting of aminopropyl vinyl ether to Si-H groups
      formed during argon plasma treatment. The amine groups were derivatized using
      pentafluorobenzaldehyde and characterized by X-ray photoelectron spectroscopy.
      The graft yield was about 3% grafted molecules within the depth of the analysis.
      The terminal aldehyde groups of diazotized heparin was also coupled to the
      primary amines. This led to a silicone elastomer with covalently bonded heparin
      which was expected to be hydrolytically stable. This method of bonding primary
      amines to the surface of silicone elastomers and the subsequent coupling of
      aldehyde-containing molecules is a promising way of obtaining novel biomaterials.

PMID- 12523860
TI  - Kinetic chain lengths in highly cross-linked networks formed by the
      photoinitiated polymerization of divinyl monomers: a gel permeation
      chromatography investigation.
AB  - Highly cross-linked networks formed by the photoinitiated polymerization of
      multifunctional monomers are finding application in the field of biomaterials
      because of their chemical versatility, reaction control, and ability to
      polymerize under physiological conditions. Typically, degradation is introduced
      into these networks via the cross-links and leads to the release of nondegradable
      but water-soluble kinetic chains formed during the chain polymerization process.
      In this study, gel permeation chromatography (GPC) was used to characterize
      kinetic chain length distributions in highly cross-linked systems that are being
      developed for orthopedic applications. By polymerizing divinyl monomers to
      various conversions and subsequently degrading them, we investigated the aspects
      of network structural evolution related to kinetic chain formation. In general,
      the average kinetic chain length increased with conversion until the onset of
      autodeceleration, when the kinetic chains decreased in length as the propagation
      reaction became diffusion-controlled. The distribution of kinetic chains also
      changed when different initiation conditions (i.e., initiator concentration and
      incident light intensity) were used, and a decrease in the kinetic chain lengths
      was observed at higher initiation rates. Finally, kinetic chain lengths were
      examined as a function of depth in thick samples polymerized with different light
      intensities and with a photobleaching initiator. Light attenuation through the
      sample led to different initiation rates as a function of depth and,
      consequently, spatial heterogeneity in the network structure as measured by the
      distributions of kinetic chains.

PMID- 12523861
TI  - Immobilization of galactose ligands on acrylic acid graft-copolymerized
      poly(ethylene terephthalate) film and its application to hepatocyte culture.
AB  - Surface modification of argon-plasma-pretreated poly(ethylene terephthalate)
      (PET) films via UV-induced graft copolymerization with acrylic acid (AAc) was
      carried out. Galactosylated surfaces were then obtained by coupling a galactose
      derivative (1-O-(6'-aminohexyl)-D-galactopyranoside) to the AAc graft chains with
      the aid of a water-soluble carbodiimide (WSC) and N-hydroxysulfosuccinimide
      (sulfo-NHS). The modified PET films were characterized by X-ray photoelectron
      spectroscopy (XPS), atomic force microscopy (AFM), and water contact-angle
      measurements. The galactosylated PET films were used as substrates for hepatocyte
      culture. The effects of surface carboxyl group concentration on the extent of
      galactose ligand immobilization, the extent of hepatocyte attachment, and the
      surface morphology were investigated. The amount of the galactose ligands
      immobilized on the PET surface increased with the AAc polymer graft
      concentration. AFM images revealed that the surface roughness of the PET film
      increased after graft copolymerization with AAc, but did not change appreciably
      with the subsequent immobilization of the galactose ligands. At the surface
      carboxyl group concentration of about 0.56 micromol/cm(2) or galactose ligand
      concentration of about 0.51 micromol/cm(2), the hepatocyte culture on the
      galactosylated surface exhibited the optimum concentration and physiological
      functions and formed aggregates or spheroids after just 1 day of culture. The
      albumin and urea synthesis functions of these hepatocytes were comparable to or
      higher than those of the hepatocytes cultured on the collagen-modified PET
      substrates.

PMID- 12523862
TI  - Surface composition and morphology of starch, amylose, and amylopectin films.
AB  - The surfaces of solution-cast films of starch, amylose, and amylopectin were
      examined with scanning electron microscopy (SEM), atomic force microscopy (AFM),
      electron spectroscopy for chemical analysis (ESCA), and time-of-flight secondary
      ion mass spectrometry (ToF-SIMS). The surface topography visualized by SEM showed
      that amylopectin films were very smooth whereas amylose and starch films were
      rougher. It appears that crystallinity or phase separation in the bulk of the
      film affects the surface topography. AFM showed that the outmost surfaces of all
      films were covered with small protrusions, 15-35 nm wide and 1-4 nm high. Studies
      with ESCA revealed the presence of 3-8% nitrogen on the surfaces. ToF-SIMS
      indicated that the nitrogen originates from protein because ionic fragments from
      amino acids and the peptide backbone were found. Extracts from the top surface
      layer of the starch film showed protein bands in gel electrophoresis (SDS-PAGE)
      around 60 kDa, which is in the same molecular weight range as the biosynthesizing
      enzyme GBSS I present in starch granules. The proteins apparently phase separated
      during film formation and migrated to the surface, resulting in an extensive
      enrichment of proteins in the film surface, where about 8% of the protein is
      present in the top 0.01% of the film. We believe that the protrusions observed
      with AFM could be one or a few proteins aggregated side by side.

PMID- 12523863
TI  - Improvement in ductility of chitosan through blending and copolymerization with
      PEG: FTIR investigation of molecular interactions.
AB  - Chitosan is an important biomaterial used widely in medical applications. One of
      the key concerns about its use is the fragile nature of chitosan films. By
      comparing the component molecular interactions using FTIR, this study attempts to
      understand how the ductility of chitosan can be improved by blending and
      copolymerizing with poly(ethylene glycol) (PEG). An improvement in ductility was
      obtained for all compositions of blend as manifested by a decrease in modulus and
      an increase in strain at break. For comparable PEG composition (approximately
      30%), the properties of the solution-cast blend were better than those of the
      grafted copolymer. Therefore, blending may be a more efficient way to improve
      ductility of chitosan. FTIR characterization of the materials revealed subtle
      decreases in molecular interactions upon annealing the partially miscible blend.
      These may not be apparent in DSC or X-ray diffraction, yet they play a key role
      in the mechanical behavior. It appears that in the case of the graft copolymer
      the improvement in the properties comes from suppression of the crystallinity of
      each component and not from component interactions. On the other hand, in the
      blend, the improvement appears to come predominantly from the "well-dispersed",
      "kinetically trapped" phase morphology and from the intermolecular interactions.
      Therefore, annealing the blend leads to decreased intermolecular interactions,
      phase coarsening, and deterioration in properties.

PMID- 12523864
TI  - Polycaprolactone-poly(ethylene glycol) multiblock copolymers as potential
      substitutes for di(ethylhexyl) phthalate in flexible poly(vinyl chloride)
      formulations.
AB  - New high-molecular-weight hydrophobic/hydrophilic segmented copolymers of
      poly(ester ether carbonate) structure, containing poly(epsilon-caprolactone)
      (PCL) and poly(ethylene glycol) (PEG) segments in their main chain, were
      synthesized and characterized. These copolymers were obtained by a two-step chain
      extension reaction carried out in the presence of alpha,omega-dihydroxy-oligoPCL
      of molecular weight 1250 and PEG samples of molecular weight 150, 400, 600, 1000,
      and 2000. The molecular structures of all synthesized materials were
      characterized by means of (1)H NMR and (13)C NMR spectroscopy, their molecular
      weights were determined by means of size exclusion chromatography, and their
      thermal properties were obtained by means of differential scanning calorimetry
      (DSC) and dynamic mechanical analysis (DMA). The poly(ester ether carbonate)s of
      this study are partly or totally miscible at least up to 50 wt % with poly(vinyl
      chloride) (PVC) and could be used to produce flexible PVC formulations. The
      miscibility between PVC and the poly(ester ether carbonate)s reported in this
      paper was investigated by means of DSC and DMA analysis. PVC blends were also
      analyzed by determining their swellability and the amount of extractables in
      aqueous media. By comparison purposes, the chain-extension product of PCL1250,
      that is, PCL polycarbonate, was also synthesized and characterized. The results
      obtained demonstrated that the copolymers with shortest PEG segment length, i.e.
      PEG150, 400, and 600, give the best results in terms of miscibility with PVC and
      lead to blends with maximum resistance to extraction by water. Therefore, they
      represent, in principle, good substitutes for low-molecular-weight, leachable PVC
      plasticizers, such as di(ethylhexyl) phthalate.

PMID- 12523865
TI  - Hyaluronic acid N-deacetylase assay in whole skin.
AB  - Hyaluronic acid (HA) N-deacetylase(s) was quantified in whole skin, using a novel
      method that involved reaction of skin with exogenous HA as substrate. Acetyl
      (CH(3)CO-) moieties generated were converted chemically to MeOAc and quantified
      using gas chromatography/mass spectrometry. HA (1.7 mg) and skin (1.0 g) yielded
      3.32 and 769.00 microg of MeOAc from the 69.0- and 76.5-year-old-patient samples,
      respectively. Without added HA, 194.00 microg of product was obtained from the
      76.5-year-old-patient samples. With chondroitin as substrate, the yields were
      2.89 and 818.04 microg of MeOAc from the 69.0- and 76.5-year-old-patient samples,
      respectively. The K5 (capsular, Escherichia coli polysaccharide) substrate
      yielded no detectable product, except for 170.02 microg from the 76.5-year-old
      patient samples. This highly sensitive method was used to demonstrate that human
      skin-HA N-deacetylase(s) was first detectable at 69 years of age, highly active
      at 76.5 years of age, and specific for N-acetyl moieties of d-GlcNAc and d-GalNAc
      where C(1) is beta-linked as in HA and CH.

PMID- 12523866
TI  - The metabolic syndrome: psychopharmacologists should weigh the evidence for
      weighing the patient.
AB  - We are in the midst of a North American epidemic of obesity and type 2 diabetes.
      Since patients with psychiatric disorders who receive psychopharmacologic
      treatments may be at even greater risk than the general population for weight
      gain, dyslipidemia, and diabetes and their complications, psychopharmacologists
      now need standards for how to monitor and manage these risks.

PMID- 12523867
TI  - Testosterone therapy in late-life major depression in males.
AB  - BACKGROUND: Major depression associated with aging in males may improve with
      anabolic/androgenic steroid therapy. The efficacy and safety of testosterone
      therapy in the treatment of depression in elderly hypogonadal males is
      inconclusive. The following study identifies a subgroup of elderly depressed
      males who may benefit from testosterone therapy. METHOD: Participants included 16
      elderly eugonadal males with major depressive disorder (DSM-IV criteria) and a
      Hamilton Rating Scale for Depression (HAM-D) score > 18. Following a single-blind
      2-week placebo lead-in, patients were randomly assigned to treatment with either
      a physiologic dose of testosterone cypionate (TC), 100 mg/week, or
      supraphysiologic dose of 200 mg/week IM for 6 weeks. Psychometric testing was
      carried out at entry into the study, at the TC injection baseline, and every 2
      weeks thereafter. Tests included an objective measurement, the HAM-D, and the
      Buss-Durkee Hostility Inventory. RESULTS: One patient meeting inclusion criteria
      responded during the placebo lead-in; thus, 15 patients were randomly assigned to
      treatment (100 mg/week, N = 8; 200 mg/week, N = 7). There was a 42% decrease in
      the mean HAM-D scores from 20.1 to 11.9 (p <.0001). However, the majority of the
      change was due to improvement in the 10 late-onset (< or = 45 years old)
      depression patients, whose mean HAM-D score decreased from 19.8 to 9.3 (53%),
      versus the 5 early-onset depression patients, whose mean HAM-D score decreased
      from 20.8 to 17.0 (18%) (p =.0110). The TC dose did not affect the response.
      Similar HAM-D decreases of 43% and 41% occurred for the respective 100- and 200
      mg/week doses. The HAM-D responder analysis found that none of 5 early-onset
      patients had HAM-D response, whereas 6 (60%) of 10 late-onset patients responded
      (p =.025). Similarly, none of the early-onset patients experienced a remission
      whereas 5 (50%) of the late-onset patients were categorized as remitters (p
      =.053). Correlations between the peak and mean total testosterone concentrations
      and HAM-D change scores suggested that only minimal TC doses were required to
      produce an antidepressant effect. CONCLUSION: These data suggest that
      testosterone therapy would best be limited to men with late-onset depression. The
      findings suggest that short-term therapy with TC is safe. Long-term treatment
      safety is unknown. Psychiatrists using testosterone therapy should ascertain that
      patients have been recently valuated for prostate cancer. If testosterone therapy
      is initiated, serial serum prostate-specific antigen sampling should be used for
      monitoring patients' prostate status.

PMID- 12523868
TI  - A randomized comparison of high-charge right unilateral electroconvulsive therapy
      and bilateral electroconvulsive therapy in older depressed patients who failed to
      respond to 5 to 8 moderate-charge right unilateral treatments.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is the treatment of choice in some
      older patients with severe depression. When compared with younger depressed
      patients, older patients have been shown to be as likely to respond to ECT but
      more likely to develop cognitive impairment. This study addresses whether adults
      aged 50 years and over who have already failed to respond to at least 5 moderate
      charge right unilateral (RUL) ECT treatments (150% above seizure threshold) are
      more likely to benefit from a switch to high-charge RUL ECT (450% above
      threshold) or to bilateral (BL) ECT. METHOD: Twenty-four patients who were
      treated with 5 to 8 moderate-charge RUL ECT treatments and who failed to improve
      sufficiently were randomly assigned to receive either BL ECT (N = 11) or high
      charge RUL ECT (N = 13). Depressive (24-item Hamilton Rating Scale for
      Depression) and cognitive scores (Mini-Mental State Examination [MMSE]) were
      compared under double-blind conditions at 3 phases of treatment. RESULTS:
      Patients in the BL ECT group exhibited significantly greater cognitive impairment
      (mean MMSE score decrease of 1.13) than those receiving high-charge RUL ECT (mean
      MMSE increase of 1.71). There were no statistically significant differences in
      clinical response to BL or high-charge RUL ECT (63.6% and 61.5%, respectively) or
      in depressive symptom remission (18.1% and 46.2%). CONCLUSION: These results
      suggest that older patients who fail to respond to moderate-charge RUL ECT may
      benefit from a switch to high-charge RUL ECT rather than BL ECT. Larger future
      studies will be needed to compare clinical response in patients switched from
      moderate-dose RUL ECT to higher-dose RUL or to BL ECT.

PMID- 12523869
TI  - Comorbidity of obsessive-compulsive disorder and depression: prevalence, symptom
      severity, and treatment effect.
AB  - BACKGROUND: The goal of this study was to investigate the co-occurrence of
      depressive disorders in obsessive-compulsive disorder (OCD) and the effect of
      these disorders on combined pharmacologic and behavioral treatment for OCD.
      METHOD: A retrospective chart analysis was performed on baseline ratings of 120
      OCD patients and posttreatment ratings of 72 of these patients. For depressive
      symptoms, the Montgomery-Asberg Depression Rating Scale and the Self-Rating
      Depression Scale were applied; for obsessive-compulsive symptoms, the Yale-Brown
      Obsessive Compulsive Scale and the Maudsley Obsessive Compulsive Inventory were
      used; and for general anxiety symptoms, the Self-Rating Anxiety Scale, the
      Clinical Anxiety Scale, and the State-Trait Anxiety Inventory were given.
      RESULTS: One third of the OCD patients in our sample were found to be depressed.
      Symptom severity on OCD symptoms at baseline did not differ between depressed and
      nondepressed OCD patients; on general anxiety symptoms, the comorbid group was
      more severely affected. Both depressed and nondepressed OCD patients responded
      well to treatment, as reflected in assessments for depressive, obsessive
      compulsive, and general anxiety symptoms. However, comorbid depression had a
      negative effect on treatment: depressed OCD patients showed less improvement than
      nondepressed OCD patients on most scales. CONCLUSION: Depression frequently
      accompanies OCD and appears to affect treatment outcome negatively. While both
      groups of patients improved with combination treatment, the OCD-alone group had
      more improvement than the group that had comorbid depression.

PMID- 12523870
TI  - Traumatic grief treatment: case histories of 4 patients.
AB  - BACKGROUND: Traumatic grief treatment is a newly developed intervention for a
      debilitating bereavement-related condition. Traumatic grief treatment uses
      imaginal and in vivo exposure techniques to target emotional distress and
      behavioral avoidance hypothesized to be core features of the syndrome, along with
      interpersonal psychotherapy techniques to engage patients and maintain rapport.
      The present report describes 4 case histories of patients treated in this way.
      METHOD: Each patient met our criterion for traumatic grief, defined as a score of
      at least 25 on the Inventory of Complicated Grief. Additionally, all 4 patients
      met DSM-IV criteria for a current episode of major depression and 1 patient for
      bipolar II disorder. The treatment course followed a direct replication design
      and ranged from 14 to 18 weekly 60- to 90-minute sessions. RESULTS: These 4 cases
      illustrate reduction in distress during exposure to painful emotional memories
      and avoided situations that was associated with decreased scores on measures of
      traumatic grief, depression, and anxiety and increased participation in and
      enjoyment of daily-life activities. CONCLUSION: Case histories of traumatic grief
      treatment suggest it is a promising treatment for individuals suffering from
      traumatic grief. It appears that imaginal relieving and in vivo exposure are
      effective in reducing grief intensity and lead to reduction in symptoms.

PMID- 12523871
TI  - Predictors of noncompliance in patients with schizophrenia.
AB  - BACKGROUND: Around 50% of patients with schizophrenia do not fully comply with
      treatment, and noncompliance is linked to relapse, rehospitalization, poor
      outcome, and high economic costs. The health belief model views noncompliance as
      a decision made by the patient, arrived at after weighing the perceived risks and
      benefits of treatment. DATA SOURCES: A MEDLINE search for the years 1980-2002
      using combinations of the keywords schizophrenia, compliance, adherence,
      antipsychotics, tolerability, and side effects was used to identify articles
      investigating the factors influencing compliance in schizophrenia. RESULTS: Many
      factors influence compliance, including those that affect patients' beliefs about
      their illness and the benefits of treatment (e.g., insight into illness, belief
      that medication can ameliorate symptoms), perceived costs of treatment (e.g.,
      medication side effects), and barriers to treatment (e.g., ease of access to
      treatment, degree of family or social support). Medication side effects that are
      distressing to patients and linked to noncompliance include extrapyramidal side
      effects, neuroleptic dysphoria, akathisia, sexual dysfunction, and weight gain.
      Compliance can be improved by cognitive-behavioral therapies, such as compliance
      therapy, and other psychosocial interventions associated with improved social
      functioning and a lower risk of rehospitalization. Treatment adherence may also
      be improved by use of atypical antipsychotics with few perceived side effects.
      CONCLUSION: By considering the factors leading to noncompliance and adopting a
      comprehensive strategy for improving compliance, encompassing psychosocial
      intervention and optimum choice of medication, the management of schizophrenia
      could be greatly improved.

PMID- 12523872
TI  - Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical
      features and treatment outcome.
AB  - BACKGROUND: Notwithstanding the emerging literature on comorbidity between
      obsessive-compulsive disorder (OCD) and bipolar disorder, relatively few
      systematic data exist on the clinical characteristics of this interface and its
      treatment. The aim of the present study is to address this challenge as it
      appears in a setting of routine clinical practice. METHOD: The sample comprised
      68 patients with comorbid DSM-IV diagnoses of OCD and major depressive episode
      admitted and treated at the day-hospital in the Department of Psychiatry at the
      University of Pisa (Pisa, Italy) during a 3-year period (January 1995-December
      1998). Thirty-eight patients (55.8%) showed lifetime comorbid bipolar disorder
      (12 [31.6%] bipolar I and 26 [68.4%] bipolar II). Diagnoses and clinical features
      were collected by means of structured (Structured Clinical Interview for DSM-IV)
      and semistructured interviews (OCD-Interview). Assessments of drug treatments,
      clinical outcome, and adverse effects were made prospectively as part of routine
      clinical care throughout the course of their day-hospitalization. RESULTS: In
      contrast with non-bipolar OCD patients, OCD-bipolar patients showed a more
      episodic course with a greater number of concurrent major depressive episodes.
      They reported a significantly higher rate of sexual obsessions and significantly
      lower rate of ordering rituals. Furthermore, they reported more frequent current
      comorbidity with panic disorder-agoraphobia and abuse of different substances
      (alcohol, sedatives, nicotine, and coffee). Drug treatment with clomipramine and,
      to a lesser extent, with selective serotonin reuptake inhibitors was associated
      with hypomanic switches in OCD-bipolar patients, especially in those not
      concomitantly treated with mood stabilizers. A combination of multiple mood
      stabilizers was necessary in 16 OCD-bipolar patients (42.1%) and a combination of
      mood stabilizers with atypical antipsychotics was required in 4 cases (10.5%).
      OCD-bipolar patients tended to show a less positive outcome for mood
      symptomatology and general functioning. Three patients required hospitalization
      for severe mixed episode. CONCLUSION: In a tertiary care center, comorbidity
      between OCD and bipolar disorder is a significant clinical problem affecting a
      large number of patients and has a substantial impact on the clinical
      characteristics and treatment outcome of both disorders.

PMID- 12523873
TI  - The risk of diabetes during olanzapine use compared with risperidone use: a
      retrospective database analysis.
AB  - BACKGROUND: The relative risk of diabetes among patients undergoing risperidone
      treatment was compared with that of patients receiving olanzapine. METHOD: A
      cohort was formed of 33,946 patients with at least 1 prescription for either
      olanzapine (N = 19,153) or risperidone (N = 14,793) between January 1, 1997, and
      December 31, 1999, recorded in the Regie de l'Assurance Maladie du Quebec
      database. Patients were excluded if clozapine was dispensed to them during the
      study period or if they were diagnosed with diabetes before beginning
      antipsychotic therapy. New diabetes diagnoses made after the first antipsychotic
      prescription during the period were tabulated until December 31, 1999; censoring
      occurred at this date or at the last service date, if there was no record of
      using services during the last 6 months of follow-up. Crude hazard ratio and
      proportional hazard analyses were carried out. RESULTS: 319 patients developed
      diabetes on olanzapine treatment, and 217 developed diabetes on risperidone
      treatment; a crude hazard ratio of 1.08 (95% CI = 0.89 to 1.31, p =.43) was
      determined. When age, gender, and haloperidol use were controlled for using
      proportional hazard analysis, there was a 20% increased risk of diabetes with
      olanzapine relative to risperidone (95% CI = 0% to 43%, p =.05). Proportional
      hazard analyses adjusted for duration of olanzapine exposure indicated that the
      first 3 months of olanzapine treatment was associated with an increased risk of
      diabetes of 90% (95% CI = 40% to 157%, p <.0001), after adjusting for age,
      gender, and haloperidol use. CONCLUSION: Compared with risperidone, olanzapine
      was associated with an increased risk of developing diabetes. More studies are
      required to further investigate this association.

PMID- 12523874
TI  - Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in
      children with attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Atomoxetine is a nonstimulant drug being studied for the treatment of
      attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a highly specific
      inhibitor of the presynaptic norepinephrine transporter with minimal affinity for
      other noradrenergic receptors or other neurotransmitter transporters or
      receptors. Results of 2 proof-of-concept studies are reported that tested the
      hypothesis that a selective inhibitor of presynaptic norepinephrine uptake would
      be effective for the treatment of ADHD in school-aged children. METHOD: Two
      identical 12-week, stratified, randomized, double-blind, placebo-controlled
      trials were conducted in children who met DSM-IV criteria for ADHD. The primary
      efficacy outcome measure was the mean change from baseline to endpoint in the
      Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) total score.
      Secondary efficacy measures included the Clinical Global Impressions-ADHD
      Severity (CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short Form
      (CPRS-R:S). RESULTS: A total of 291 patients were randomized in the 2 trials
      combined (Study 1, N = 147; Study 2, N = 144). Stimulant-naive patients were
      randomized to atomoxetine, placebo, or methylphenidate. Patients with prior
      stimulant exposure were randomized to atomoxetine or placebo. Atomoxetine
      significantly reduced ADHD RS total scores compared with placebo in each study (p
      <.001). Changes in the CGI-ADHD-S (Study 1: p =.003; Study 2: p =.001) and CPRS
      ADHD Index (Study 1: p =.023; Study 2: p <.001) also showed atomoxetine to be
      statistically significantly superior to placebo in reducing ADHD symptoms.
      Atomoxetine was found to be well tolerated in this population of pediatric
      patients. CONCLUSION: Two studies of atomoxetine early in its development
      confirmed that atomoxetine, a specific and selective inhibitor of noradrenergic
      uptake, was effective for the treatment of children with ADHD. In addition,
      atomoxetine was found to be well tolerated.

PMID- 12523875
TI  - A comparison of the efficacy, safety, and tolerability of divalproex sodium and
      olanzapine in the treatment of bipolar disorder.
AB  - BACKGROUND: This study compared the efficacy, safety, and tolerability of
      divalproex and olanzapine in the treatment of acute mania associated with bipolar
      disorder. METHOD: This randomized, 12-week, double-blind, parallel-group,
      multicenter study included DSM-IV-defined bipolar disorder type I patients
      hospitalized for acute mania and randomly assigned to treatment with divalproex
      or olanzapine. After an inpatient period of up to 21 days, subjects were followed
      as outpatients. Dose adjustment was permitted during the inpatient period.
      Efficacy was assessed using change from baseline in Mania Rating Scale (MRS)
      score to day 21; other efficacy measures included the Brief Psychiatric Rating
      Scale, the Hamilton Rating Scale for Depression, and the Clinical Global
      Impressions-Part I, Severity of Illness scale. The primary safety endpoint was
      change from baseline in weight. Other safety and tolerability endpoints included
      spontaneous adverse event reporting and changes from baseline in laboratory
      measures and vital signs. RESULTS: 120 subjects (N = 63 divalproex, N = 57
      olanzapine) were randomly assigned to treatment. No significant differences
      between groups were found for any efficacy variable for change from baseline to
      day 21. Mean MRS score changes from baseline to day 21 were -14.8 for divalproex
      and -17.2 for olanzapine (p =.210). A significantly (p <.05) greater proportion
      of olanzapine-treated subjects experienced somnolence, weight gain, edema,
      rhinitis, and speech disorder (slurred speech); no adverse events were
      significantly greater in the divalproex group. A number of laboratory measures
      also demonstrated significant treatment differences, but the clinical
      significance of many of these is uncertain. Mean body weight changes were
      significantly greater in the olanzapine group (+ 8.8 lb [+ 4.0 kg]) than the
      divalproex group (+ 5.5 lb [+ 2.5 kg], p <.050). One death occurred during the
      study (olanzapine group, diabetic ketoacidosis). CONCLUSION: No significant
      difference in efficacy was found between treatment groups. Divalproex was
      associated with a more favorable adverse event profile and significantly less
      weight gain than olanzapine.

PMID- 12523876
TI  - Efficacy of quetiapine and risperidone against depressive symptoms in outpatients
      with psychosis.
AB  - BACKGROUND: The treatment of psychotic symptoms in patients with mood disorders
      is a complex challenge. Antipsychotic medications in these individuals may be
      associated with extrapyramidal symptoms (EPS), worsening of depression, and
      functional impairment. Atypical antipsychotics such as quetiapine and risperidone
      are associated with a decreased incidence of adverse events such as EPS. The
      objective of this study was to compare the efficacy and tolerability of
      quetiapine and risperidone for the treatment of depressive symptoms in
      outpatients with psychosis. METHOD: In this 4-month, multicenter, open-label
      trial, patients were randomly assigned in a 3:1 ratio of quetiapine to
      risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses
      and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective
      disorder, bipolar I disorder, major depressive disorder, delusional disorder,
      Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance
      abuse dementia. Patients were classified as mood disordered if they had bipolar
      disorder, major depressive disorder, or schizoaffective disorder. Efficacy was
      assessed using the Positive and Negative Syndrome Scale and the Clinical Global
      Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to
      assess the level of depressive symptoms. The primary tolerability assessment was
      presence or absence of substantial EPS, defined as EPS severe enough to require
      an alteration in treatment. RESULTS: A total of 554 patients were randomly
      assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg
      for quetiapine and 4.4 mg for risperidone. Although both agents produced
      improvements in mean HAM-D scores, quetiapine produced a greater improvement than
      risperidone in all patients (p =.0015). Within the mood-diagnosed population,
      incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373)
      occurred significantly less frequently among patients taking quetiapine. For
      patients with non-mood diagnoses, incidences of substantial EPS were fewer for
      patients taking quetiapine than for those taking risperidone (p =.062); however,
      this was not statistically significant. CONCLUSION: These results suggest that
      quetiapine may be a useful agent in the management of depressive symptoms in
      patients with psychosis.

PMID- 12523877
TI  - An open study of olanzapine and fluoxetine for psychotic major depressive
      disorder: interim analyses.
AB  - BACKGROUND: Although atypical antipsychotic agents are commonly used in the
      treatment of psychotic depression, there are no published prospective studies on
      their use in this condition. The aim of this study was to assess, by interim
      analyses, the efficacy of the atypical antipsychotic agent olanzapine in
      combination with the selective serotonin reuptake inhibitor antidepressant agent
      fluoxetine. METHOD: We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%];
      mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive
      disorder with psychotic features into an open trial of olanzapine, 5 to 20
      mg/day, plus fluoxetine, 20 to 80 mg/day. Patients were assessed at each visit
      with the 17-item Hamilton Rating Scale for Depression and both the psychotic and
      mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders,
      Patient Edition. We are reporting the results of the first 6 weeks of treatment.
      RESULTS: Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open
      trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side
      effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic
      features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations
      alone, and 66.7% (N = 18) reported both delusions and hallucinations. In
      addition, the overall rates of response for the intent-to-treat group were as
      follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3%
      (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic
      depression remission rate, 40.7% (N = 11). CONCLUSION: The combination of
      olanzapine and fluoxetine appears to be a promising, safe, and effective
      treatment for psychotic depression. Double-blind studies are needed to confirm
      this impression.

PMID- 12523878
TI  - A prospective study of the offspring of bipolar parents responsive and
      nonresponsive to lithium treatment.
AB  - BACKGROUND: The descriptions of clinical course among bipolar youths vary
      significantly and differ markedly from the findings described in classical
      studies of bipolar adults. This difference may in part reflect genetic
      heterogeneity. Response to lithium monotherapy identifies a homogeneous subgroup
      of bipolar adults. The aim of this study was to prospectively characterize the
      clinical course, including antecedent and comorbid conditions, among the
      offspring of 2 groups of bipolar parents divided on the basis of response to
      lithium. METHOD: Parents were identified from families participating in ongoing
      molecular genetic studies and selected from specialty affective disorder clinics.
      For each child, 1 parent met Research Diagnostic Criteria/DSM-IV criteria for
      bipolar I disorder and either response or nonresponse to lithium prophylaxis. The
      other parent had no lifetime history of a major psychiatric illness. Blind to
      family affiliation and lithium response, all eligible offspring aged 10 to 25
      years were interviewed using the Schedule for Affective Disorders and
      Schizophrenia for School-Aged Children-Present and Lifetime Version (K-SADS-PL),
      and best-estimate diagnoses were made by a panel of experts. Offspring were then
      reassessed over a 5-year period. RESULTS: Offspring of lithium responders (N =
      34) had good premorbid functioning and manifested classical mood disorders with
      an episodic course. Comorbid conditions in this group remitted prior to the mood
      disorder. In contrast, offspring of lithium nonresponders (N = 21) had poorer
      premorbid functioning and manifested mood disorders with a chronic course.
      Comorbid conditions continued alongside the mood disorder. Clinical course among
      affected offspring was predicted by the disease course of the parent. CONCLUSION:
      The pattern of clinical course, remitting or nonremitting, appears to be
      inherited. Among the offspring of lithium-responsive bipolar parents, an early
      onset subgroup with a classical episodic clinical course can be identified.

PMID- 12523880
TI  - A contact lens as an artificial cornea for improved visualization during practice
      surgery on cadaver eyes.
AB  - OBJECTIVE: To describe the use of a polymethylmethacrylate contact lens as an
      artificial cornea to enhance visualization for practice surgery using cadaver
      eyes. DESIGN: The opaque cornea of a cadaver eye is removed by trephination.
      Cyanoacrylate glue is used to secure a large-diameter polymethylmethacrylate
      contact lens to the corneal rim. RESULTS: Excellent visualization for practice
      surgery is achieved with this technique. The adhesion of the contact lens to the
      cadaver eye maintains the anterior chamber sufficiently to perform
      phacoemulsification cataract extraction or pars plana vitrectomy. CONCLUSIONS:
      This technique improves visualization of the intraocular structures during
      practice surgery, thereby enhancing the ability of the learning surgeon to
      perform and practice delicate surgical maneuvers. The procedure is simple,
      effective, and inexpensive.

PMID- 12523881
TI  - Fine structural evaluation of the iris after unilateral treatment with
      latanoprost in patients undergoing bilateral trabeculectomy (the Mainz II study).
AB  - OBJECTIVE: To investigate by masked electron microscopy whether 6 months of
      topical latanoprost caused pathological changes in the peripheral iris of
      patients with glaucoma. METHODS: Seventeen patients with bilateral primary open
      angle glaucoma requiring trabeculectomy were recruited for this study. The
      iridectomy taken during surgery on the first eye served as a control. The second
      test eye was treated topically with latanoprost for 6 months before its
      trabeculectomy. Fourteen patients completed the treatment arm of the study, and 1
      of these underwent marked color change. As a result, 31 iridectomy specimens were
      fixed, coded, and evaluated. RESULTS: The specimens were evaluated for evidence
      of stromal inflammation, vascular alterations, and stromal and posterior
      epithelial degeneration. None of these features was evident in any of the 31
      iridectomy specimens. There was evidence of the incidence of free melanin
      granules in the stroma, melanin turnover, abundance of stromal clump cells,
      atypical cellular features in melanocytes, and prominence of the anterior border.
      After code breaking, it was evident that none of these features distinguished the
      test from the fellow irises in our group. The patient with color change in the
      test iris did not stand out from the others in this analysis. Qualitative
      reexamination of further sections after unmasking gave the impression of
      increased melanin granule numbers in the melanocytes of the anterior border
      region. CONCLUSIONS: The ultrastructure of the iridectomies from the latanoprost
      treated eyes and the fellow eyes conformed to published standards for normal
      iris. There was no evidence of early ultrastructural changes, which might have
      been the harbingers of latanoprost-induced iris abnormality.

PMID- 12523882
TI  - Using the arteriolar Pressure Attenuation Index to predict ocular hypertension
      progression to open-angle glaucoma.
AB  - BACKGROUND: Vascular phenomena are considered important to optic nerve and visual
      field progression in open-angle glaucoma (OAG). A recently described formulation,
      the Pressure Attenuation Index (PAI), links arteriolar caliber variations to
      pressure loss along the retinal arteriolar system. OBJECTIVE: To examine whether
      the PAI could predict ocular hypertension (OHT) progression to OAG. METHODS: The
      PAI was calculated for 27 eyes of 14 patients with OHT using initial and final
      digitized optic disc photographs taken during a follow-up interval of 5 to 18
      years. Serial stereo color disc photographs and visual fields were analyzed to
      determine progression. RESULTS: At baseline, the arteriolar tree of 8 subjects
      with OHT that progressed to OAG (n = 8 eyes) demonstrated a 45.8% greater mean
      PAI value than that of 7 subjects who did not progress (n = 7 eyes) (mean +/-
      SEM, 5.31 +/- 0.93 vs 3.64 +/- 0.34; r = 0.83). Progression was independent of
      baseline cup-disc ratio. The PAI values of subjects with stable OHT remained
      stable after a median follow-up interval of 12.0 years. The PAI values of
      subjects with OHT that progressed demonstrated a further increase of 19.97% +/-
      11.24% during a median follow-up period of 6.0 years. CONCLUSIONS: The results
      support the hypothesis that low end-arteriolar pressure predicts the progression
      from OHT to OAG. The PAI provides a new, early, reproducible, and physiological
      method to study vascular phenomena in glaucoma.

PMID- 12523883
TI  - Macular thickness changes in glaucomatous optic neuropathy detected using optical
      coherence tomography.
AB  - OBJECTIVE: To correlate macular thickness and retinal nerve fiber layer (RNFL)
      thickness in normal and glaucomatous eyes using optical coherence tomography.
      METHODS: Complete examination, automated achromatic perimetry, and optical
      coherence tomography of the peripapillary RNFL and macula were performed.
      Exclusion criteria were visual acuity of less than 20/40, diseases other than
      glaucoma, and unreliable automated achromatic perimetry. Macular thickness
      measurements were generated using 6 radial optical coherence tomographic scans
      (5.9 mm) centered on the fovea, and mean and quadrantic macular thickness values
      were calculated. RESULTS: Fifty-nine eyes of 59 patients (29 normal and 30
      glaucomatous) were enrolled (mean +/- SD age, 56.7 +/- 20.3 years; range, 20-91
      years). All eyes with glaucoma had associated visual field loss (mean +/- SD mean
      defect, -8.4 +/- 5.8 dB). Mean macular thickness was significantly associated
      with visual field mean defect (R2 = 0.47; P<.001), pattern standard deviation (R2
      = 0.32; P<.001), and mean RNFL thickness (R2 = 0.38; P<.001). In glaucomatous
      eyes with visual field loss localized to 1 hemifield (n = 11), mean +/- SD
      macular thickness in the quadrant associated with the field defect (277 +/- 28
      micro m) was significantly less (P =.005) than in the unaffected quadrant (286 +/
      27 micro m). Mean RNFL thickness in the affected quadrant (89 +/- 53 micro m)
      was significantly thinner (P =.009) than in the unaffected quadrant (121 +/- 39
      micro m). MAIN OUTCOME MEASURES: Mean total and quadrantic macular and RNFL
      thickness measurements. CONCLUSIONS: Macular thickness changes are well
      correlated with changes in visual function and RNFL structure in glaucoma and may
      be a surrogate indicator of retinal ganglion cell loss.

PMID- 12523884
TI  - Factors for glaucoma progression and the effect of treatment: the early manifest
      glaucoma trial.
AB  - OBJECTIVE: To assess factors for progression in the Early Manifest Glaucoma Trial
      (EMGT), including the effect of EMGT treatment. SETTING/PARTICIPANTS: Two hundred
      fifty-five open-angle glaucoma patients randomized to argon laser trabeculoplasty
      plus topical betaxolol or no immediate treatment (129 treated; 126 controls) and
      followed up every 3 months. METHODS: Progression was determined by perimetric and
      photographic optic disc criteria. Patient-based risk of progression was evaluated
      using Cox proportional hazard regression models and was expressed as hazard
      ratios (HR) with 95% confidence intervals (95% CI). RESULTS: After 6 years, 53%
      of patients progressed. In multivariate analyses, progression risk was halved by
      treatment (HR = 0.50; 95% CI, 0.35-0.71). Predictive baseline factors were higher
      intraocular pressure (IOP) (ie, the higher the baseline IOP, the higher the
      risk), exfoliation, and having both eyes eligible (each of the latter 2 factors
      doubled the risk), as well as worse mean deviation and older age. Progression
      risk decreased by about 10% with each millimeter of mercury of IOP reduction from
      baseline to the first follow-up visit (HR = 0.90 per millimeter of mercury
      decrease; 95% CI, 0.86-0.94). The first IOP at that visit (3 months' follow-up)
      was also related to progression (HR = 1.11 per millimeter of mercury higher; 95%
      CI, 1.06-1.17), as was the mean IOP at follow-up (HR = 1.13 per millimeter of
      mercury higher; 95% CI, 1.07-1.19). The percent of patient follow-up visits with
      disc hemorrhages was also related to progression (HR = 1.02 per percent higher;
      95% CI, 1.01-1.03). No other factors were identified. CONCLUSIONS: Patients
      treated in the EMGT had half of the progression risk of control patients. The
      magnitude of initial IOP reduction was a major factor influencing outcome.
      Progression was also increased with higher baseline IOP, exfoliation, bilateral
      disease, worse mean deviation, and older age, as well as frequent disc
      hemorrhages during follow-up. Each higher (or lower) millimeter of mercury of IOP
      on follow-up was associated with an approximate 10% increased (or decreased) risk
      of progression.

PMID- 12523885
TI  - Intravitreal injection of triamcinolone for diffuse diabetic macular edema.
AB  - OBJECTIVE: To evaluate the clinical outcome of an intravitreal injection of
      triamcinolone acetonide as treatment of diffuse diabetic macular edema.
      PARTICIPANTS: This prospective, interventional, clinical case series study
      included 20 patients (26 eyes) who received an intravitreal injection of 25 mg of
      triamcinolone acetonide for treatment of diffuse diabetic macular edema. Mean +/-
      SD follow-up time was 6.64 +/- 6.10 months. The study group was compared with a
      control group of 16 patients who underwent macular grid laser coagulation. MAIN
      OUTCOME MEASURES: Visual acuity and intraocular pressure. RESULTS: In the study
      group, visual acuity improved significantly (P<.001), from 0.12 +/- 0.08 at
      baseline to a maximum of 0.19 +/- 0.14 during follow-up. Seventeen (81%) of 21
      eyes with a follow-up period of more than 1 month had improved visual acuity. In
      the control group, visual acuity did not change significantly. In the study
      group, intraocular pressure increased significantly (P<.001), from 16.9 +/- 2.5
      mm Hg to a mean maximal value of 21.3 +/- 4.7 mm Hg, and decreased significantly
      (P =.03) to 17.7 +/- 4.7 mm Hg at the study's end. CONCLUSION: Intravitreal
      injection of 25 mg of triamcinolone acetonide may be beneficial for improving
      visual acuity in patients with clinically significant diffuse diabetic macular
      edema.

PMID- 12523886
TI  - Idiopathic recurrent neuroretinitis: effects of long-term immunosuppression.
AB  - OBJECTIVE: To determine the efficacy of long-term immunosuppressive therapy in
      patients with recurrent idiopathic neuroretinitis. METHODS: A retrospective
      review of 30 patients with recurrent idiopathic neuroretinitis identified 7 who
      received ongoing immunosuppression with prednisone and/or azathioprine for whom
      adequate follow-up information was available. We calculated the number of attacks
      per unit of time for each patient before and after treatment to derive mean
      attack rates for the group. RESULTS: For the entire group, we found a rate of
      0.58 attacks per year prior to the initiation of immunosuppressive treatment,
      which decreased to 0.16 attacks per year following immunosuppression. This
      represents a reduction in the attack rate of 0.41, or a 72% decrease in attack
      frequency. CONCLUSIONS: Our study suggests a possible role for long-term
      immunosuppressive treatment in patients with recurrent idiopathic neuroretinitis.
      A longer follow-up interval, more standardized treatment regimens, and additional
      outcome measures might reveal a greater benefit of treatment.

PMID- 12523887
TI  - Tumor basal area and metastatic death after proton beam irradiation for choroidal
      melanoma.
AB  - BACKGROUND: Tumor dimension is an established prognostic factor for metastasis
      related death after radiotherapy for uveal melanoma. OBJECTIVE: To compare
      various methods of modeling the relationship between tumor dimension and
      metastatic death. PATIENTS AND METHODS: The analyses were based on a consecutive
      series of 1204 patients with primary choroidal melanoma treated with proton beam
      irradiation (70 cobalt-gray equivalent in 5 fractions) at the Harvard Cyclotron
      Laboratory, Boston, Mass, between January 1985 and December 1998. Largest basal
      diameter and largest perpendicular basal diameter were recorded at the time of
      surgical placement of tantalum rings used for tumor localization during proton
      treatment. The height of the tumor and the axial diameter of the eye were
      measured by ultrasonography prior to treatment. Using proportional hazards
      regression, we compared the prognostic influence of different indices of tumor
      size with estimated risk ratios and death rates according to tumor basal area and
      largest basal diameter. All estimates were adjusted for other established
      prognostic factors. RESULTS: Patients were followed up annually through June 30,
      2000. Of the 1204 patients analyzed, 193 died of melanoma metastasis. The median
      follow-up among survivors was 7.9 years. The 5- and 10-year metastatic death
      rates were 12.8% and 20.7%, respectively. Among various approaches for modeling
      tumor dimension, the logarithm of tumor basal area had the highest log-likelihood
      and performed better than other approaches in 85% of the simulations. Based on
      this model, the covariate-adjusted rate ratio for any doubling in tumor basal
      area was 1.92 (95% confidence interval, 1.62-2.28). CONCLUSION: Tumor basal area
      is a better prognostic indicator than largest tumor diameter and tumor volume in
      the prediction of metastatic death after proton beam irradiation for uveal
      melanoma.

PMID- 12523888
TI  - Optic nerve tissue shrinkage during pathologic processing after enucleation for
      retinoblastoma.
AB  - OBJECTIVES: To quantify and analyze the differences between the length of the
      optic nerve as measured by the ophthalmologist in the operating room after
      enucleation and the length as measured by the pathologist after fixation.
      METHODS: The authors performed a retrospective review of patients who underwent
      either primary or secondary enucleation for retinoblastoma at the Ophthalmic
      Oncology Center of the New York-Presbyterian Hospital-Cornell campus between
      November 1979 and August 2001. Intraoperative notes and pathologic reports were
      reviewed to determine the length of the resected optic nerve as recorded by both
      the surgeon and pathologist. RESULTS: Sufficient data for inclusion in the study
      were available from 100 enucleation specimens belonging to 96 patients. A
      significant degree of shrinkage of the optic nerve occurred after fixation, with
      a mean shrinkage of 30.3% from the time of enucleation to the time of measurement
      by the pathologist. Age at enucleation affected the degree of optic nerve
      shrinkage; nerves from younger children underwent more shrinkage than nerves from
      older patients. Sex of the patient and the laterality of disease did not
      significantly affect optic nerve shrinkage. CONCLUSIONS: A significant degree of
      shrinkage of the optic nerve occurs in retinoblastoma enucleation specimens after
      fixation prior to pathologic analysis. This finding must be taken into account
      when comparing different series and making recommendations for chemoprophylaxis
      based solely on histopathologic examination.

PMID- 12523889
TI  - Final nasolacrimal ostium after external dacryocystorhinostomy.
AB  - OBJECTIVE: To evaluate the nasolacrimal ostium created after successful external
      dacryocystorhinostomy. METHODS: This prospective study included 41 successful
      primary external dacryocystorhinostomies performed in 41 patients with
      nasolacrimal duct obstruction (33 women and 8 men; age range, 19-75 years). The
      dimensions of osteotomy were measured during surgery. Patients alternately
      underwent either anterior only or anterior and posterior flap anastomosis between
      the lacrimal sac and the nasal mucosa. Digital subtraction macrodacryocystography
      was performed to assess the nasolacrimal ostium 6 months after surgery. RESULTS:
      Dacryocystography showed that the lacrimal sac had re-formed in 40 (98%) of 41
      patients. The nasolacrimal ostium was located at the inferior part of the re
      formed sac in 37 patients (90%) and at the middle part of the re-formed sac in 3
      patients (7%). Mean ostium heights were 3.8 mm (range, 1.6-6.5 mm) in patients
      who underwent anterior flap anastomosis and 3.1 mm (range, 1.2-5.2 mm) in those
      who underwent both anterior and posterior flap anastomosis (P =.22). Ostium
      height did not correlate with osteotomy size (mean, 183 mm2; range, 132-266 mm2;
      P =.10). CONCLUSIONS: This study confirms that after successful
      dacryocystorhinostomy, the nasolacrimal anastomosis contracts into a relatively
      small ostium. Contrary to common belief, the lacrimal sac often re-forms after
      surgery. The final ostium frequently develops at the inferior part of the
      regenerated sac. Suturing the posterior lacrimal and nasal flaps in addition to
      the anterior flaps does not significantly affect the ultimate ostium size.

PMID- 12523890
TI  - Galectin-7 as a potential mediator of corneal epithelial cell migration.
AB  - OBJECTIVE: To assess the role of a carbohydrate-binding protein, galectin-7, in
      reepithelialization of corneal wounds. METHODS: Transepithelial excimer laser
      ablations were performed on mouse corneas, and the wounds were allowed to
      partially heal in vivo for 18 to 22 hours. At the end of the healing period,
      expression levels of galectin-7 messenger RNA and protein were analyzed using
      semiquantitative reverse transcriptase-polymerase chain reaction, Western blot
      analysis, and immunohistochemical localization studies. To determine the effect
      of exogenous galectin-7 on reepithelialization of corneal wounds, corneas with 2
      mm alkali burn wounds were allowed to partially heal in vitro for 20 to 24 hours
      in serum-free media in the presence or absence of recombinant galectin-7. At the
      end of the healing period, the wound areas were photographed and quantified.
      RESULTS: Expression of galectin-7 messenger RNA and protein was markedly up
      regulated in the corneal epithelium after injury. Exogenous galectin-7 stimulated
      reepithelialization of corneal wounds. The stimulatory effect of galectin-7 on
      corneal epithelial wound closure was specifically inhibited by a competing sugar,
      beta-lactose, but not by an irrelevant disaccharide, sucrose. CONCLUSIONS:
      Galectin-7 has the potential to mediate corneal epithelial cell migration and
      reepithelialization of wounds. CLINICAL RELEVANCE: These findings have broad
      implications for developing novel, galectin-based, therapeutic strategies for
      treatment of nonhealing corneal epithelial defects.

PMID- 12523891
TI  - Effect of WIN 55212-2, a cannabinoid receptor agonist, on aqueous humor dynamics
      in monkeys.
AB  - OBJECTIVE: To evaluate the effects of WIN 55212-2, a cannabinoid receptor
      agonist, on intraocular pressure and aqueous humor dynamics in normal monkeys and
      monkeys with glaucoma. METHODS: Intraocular pressure was measured prior to and up
      to 6 hours after the topical administration of WIN 55212-2 to 1 eye of 5 normal
      monkeys and to the glaucomatous eye of 8 monkeys with unilateral laser-induced
      glaucoma. Tonographic outflow facility and fluorophotometric flow rates of
      aqueous humor were measured in 6 normal monkeys before and after treatment.
      RESULTS: In normal monkeys, a single dose of WIN 55212-2 reduced intraocular
      pressure for 4, 5, or 6 hours, with a maximum reduction of 1.4 +/- 0.4 (mean +/-
      SEM) mm Hg, 2.9 +/- 0.4 mm Hg, and 3.4 +/- 0.6 mm Hg following the 0.07%, 0.2%,
      and 0.5% concentrations, respectively (P =.08). In 8 glaucomatous monkey eyes,
      the ocular hypotensive effect was maintained for 5 days with twice-daily
      administration of 0.5% WIN 55212-2. Outflow facility was unchanged (P =.34) and
      aqueous humor flow was decreased by 18% (P =.04) in the treated eyes compared
      with vehicle-treated contralateral control eyes in normal monkeys. CONCLUSIONS:
      WIN 55212-2, a cannabinoid agonist at the CB(1) receptor, reduces intraocular
      pressure in both normal and glaucomatous monkey eyes. A decrease of aqueous flow
      appears to account for the intraocular pressure reduction in normal monkey eyes.
      CLINICAL RELEVANCE: Cannabinoid agonists at the CB(1) receptor, a new class of
      antiglaucoma agents that is different from currently used clinical drugs, may
      have clinical potential.

PMID- 12523892
TI  - Pathogenesis of the vitreous cloud emanating from subretinal hemorrhage.
AB  - OBJECTIVE: To determine the cellular mechanism that allows subretinal hemorrhage
      to cloud the vitreous. METHODS: We simulated subretinal hemorrhage in a rabbit
      model by injecting autologous blood beneath the retina. At the first appearance
      of a cloud in the vitreous a vitrectomy was performed and using a surgical
      microscope, the retina was searched for breaks. After enucleation and fixation,
      the retina was searched for microscopic breaks using light and electron
      microscopy. The vitreous was then examined to determine the character of the cell
      population in the cloud. In a related study, we sampled and examined the vitreous
      for its cellular content in patients undergoing vitrectomy to clear cloudy
      vitreous emanating from subretinal hemorrhage. RESULTS: We found no breaks in the
      living retina of the animal models or the patients. Microscopic examination of
      serial sections of the rabbit retina revealed necrosis except for the internal
      limiting membrane. Fragments of the erythrocytes were seen within the damaged
      retina and on both sides of the internal limiting membrane. Electron microscopy
      suggested that the erythrocytic fragments had migrated across the internal
      limiting membrane. The vitreous cloud in both rabbits and patients contained only
      fragments of erythrocytes. CONCLUSIONS: Thick subretinal hemorrhage causes
      necrosis of the overlying retina. Fragments of the erythrocytes infiltrate the
      retina and cross an intact internal limiting membrane to cloud the vitreous.
      CLINICAL RELEVANCE: Rapid necrosis of the retina occurs over thick subretinal
      hemorrhage and indicates the need for early displacement of the hemorrhage from
      the macula if function is to be preserved and breakthrough prevented.

PMID- 12523894
TI  - Prevention of herpes simplex virus eye disease: a cost-effectiveness analysis.
AB  - OBJECTIVES: To estimate the cost of treating herpes simplex virus (HSV) eye
      disease, and to evaluate the incremental cost-effectiveness of chronic
      suppressive antiviral prophylaxis for reducing ocular HSV recurrences. METHODS:
      An economic decision-tree model was used on follow-up data from 703 patients with
      prior ocular HSV disease who were enrolled in a Herpetic Eye Disease Study
      multicenter clinical trial that evaluated the prolonged use of oral acyclovir.
      Costs were based on wholesale drug prices, Medicare fees, and national health
      surveys. Incremental cost-effectiveness ratios for all patients and for patients
      with prior stromal keratitis were calculated as the additional net cost of
      acyclovir prophylaxis compared with the number of cases of ocular herpes
      prevented during 12 months. One- and 2-way sensitivity analyses evaluated the
      effect of different treatment costs and recurrence risks. RESULTS: Approximately
      17.7 US dollars million is expended annually to treat the estimated 59,000 new
      and recurrent episodes of HSV eye disease occurring among 29,000 individuals each
      year in the United States. Chronic suppressive oral acyclovir costs 8532 US
      dollars per ocular HSV episode averted. The incremental cost per infection
      averted would decline by up to 51% if antiviral prophylaxis were more effective
      and by up to 87% if patients had a higher recurrence risk. Targeting prophylaxis
      to patients with a history of stromal keratitis is not more cost-effective than
      providing oral acyclovir for patients with any prior HSV eye disease.
      CONCLUSIONS: Herpetic eye disease is costly to treat and prevent. Because
      prophylactic oral acyclovir is not a cost-effective option for all patients with
      previous HSV eye disease, therapeutic decisions must be made on a case-by-case
      basis.

PMID- 12523895
TI  - Economic analysis in eye disease.

PMID- 12523893
TI  - Visual loss in patients with cytomegalovirus retinitis and acquired
      immunodeficiency syndrome before widespread availability of highly active
      antiretroviral therapy.
AB  - OBJECTIVE: To evaluate rates and causes of visual loss among patients with
      acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis
      before widespread availability of highly active antiretroviral therapy (HAART).
      METHODS: Data from 681 patients with AIDS and newly diagnosed or relapsed CMV
      retinitis who enrolled in 3 clinical trials conducted by the Studies of Ocular
      Complications of AIDS (SOCA) Research Group (between 1990 and 1996) were combined
      to evaluate the rates and causes of visual loss. Visual acuity and visual field
      (Goldmann visual fields) losses were evaluated. RESULTS: The rates of visual loss
      in eyes with CMV retinitis were substantial in all 3 clinical trials, ranging
      from 51.7 to 97.7 events per 100 eye-years for loss of visual acuity to worse
      than 20/40 and 18.9 to 49.1 events per 100 eye-years for loss of visual acuity to
      20/200 or worse. The 2 major causes of visual loss were retinitis, involving
      either the macula or the optic nerve, and retinal detachment. After 1992, visual
      outcomes improved significantly. Antiretroviral therapy was associated with a 30%
      reduction in the risk of visual acuity loss (relative risk, 0.70; P =.02).
      CONCLUSIONS: In the pre-HAART era, visual morbidity was substantial. However,
      there was a secular trend for improved outcomes. The principal causes of visual
      loss were CMV involvement of the posterior retina and retinal detachment.

PMID- 12523896
TI  - Corneal juvenile xanthogranuloma in a 4-month-old child.

PMID- 12523897
TI  - Conjunctival keratoacanthoma in an Asian.

PMID- 12523898
TI  - An unusual case of leukocoria: heterotopic brain arising from the retina.

PMID- 12523899
TI  - Ocular hypotony secondary to spontaneously ruptured posterior staphyloma.

PMID- 12523900
TI  - Primary orbital angiomatous meningioma.

PMID- 12523901
TI  - Nonarteritic anterior ischemic optic neuropathy associated with acute glaucoma
      secondary to Posner-Schlossman syndrome.

PMID- 12523902
TI  - Traumatic retinal break from viscoelastic cannula during cataract surgery.

PMID- 12523903
TI  - Bilateral serous retinal detachments following diode laser treatment for
      retinopathy of prematurity.

PMID- 12523904
TI  - Retinal pigment epithelium tumorlike lesion arising from an area treated with
      laser photocoagulation.

PMID- 12523905
TI  - Macular translocation with 360 degrees peripheral retinectomy for geographic
      atrophy.

PMID- 12523906
TI  - Presumed teratoma-associated paraneoplastic retinopathy.

PMID- 12523907
TI  - Isolated anterior uveitis as the initial sign of systemic candidemia.

PMID- 12523908
TI  - Bilateral orbital myeloid sarcoma as initial sign of acute myeloid leukemia: case
      report and review of the literature.

PMID- 12523909
TI  - Minocycline-induced ocular pigmentation.

PMID- 12523910
TI  - Central serous chorioretinopathy exhibiting a vitelliform lesion similar to best
      disease.

PMID- 12523911
TI  - Temporary tarsorrhaphy: a valuable procedure in Hansen disease.

PMID- 12523912
TI  - Advice for young physicians.

PMID- 12523913
TI  - Demystifying idiopathic interstitial pneumonia.
AB  - Careful histopathological evaluation has shown the traditionally clinical
      diagnosis of idiopathic interstitial pneumonia to be more heterogeneous than once
      thought. Its subclassification, based on clinicopathological criteria, has
      important therapeutic and prognostic implications. The most important distinction
      is the presence of usual interstitial pneumonia, the histopathological pattern
      seen in idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis has a worse
      response to therapy and prognosis. New insight into the pathophysiology of
      idiopathic pulmonary fibrosis suggests a distinctly fibroproliferative process,
      and antifibrotic therapies show promise. Although the clinical and radiographic
      diagnosis of idiopathic pulmonary fibrosis can be made confidently in some cases,
      many patients require surgical lung biopsy to determine their underlying
      histopathological pattern. A structured, clinicopathological approach to the
      diagnosis of idiopathic interstitial pneumonia, with particular attention to the
      identification of idiopathic pulmonary fibrosis, ensures proper therapy, enhances
      prognosis, and allows for further investigation of therapies aimed at the
      distinct pathophysiology.

PMID- 12523914
TI  - Cardiovascular disease in type 2 diabetes mellitus: current management
      guidelines.
AB  - Cardiovascular disease is the most prevalent and detrimental complication of
      diabetes mellitus. The incidence of cardiovascular mortality in diabetic subjects
      without a clinical history of previous cardiac events is as high as the incidence
      in nondiabetic subjects with a history of myocardial infarction. This inordinate
      increase in the risk of coronary events in diabetic patients is attributed to
      multiple factors, including glycation and oxidation of proteins and increased
      prevalence of classic risk factors of coronary disease, such as hypertension,
      obesity, and dyslipidemia. Despite advances in the management of cardiovascular
      disease, a large proportion of diabetic subjects continue to have uncontrolled
      hyperglycemia, hypertension, and dyslipidemia. In addition, certain medical
      interventions with established efficacy in the general population do not appear
      to be appropriate for diabetic subjects. Recently published clinical trials of
      managing coronary risk factors indicate that more stringent goals of therapy
      should be set for diabetic patients. In this communication, some of these
      landmark studies are reviewed and some practical guidelines of management are
      suggested.

PMID- 12523915
TI  - Marked improvement in nocturnal gastroesophageal reflux in a large cohort of
      patients with obstructive sleep apnea treated with continuous positive airway
      pressure.
AB  - BACKGROUND: Nocturnal gastroesophageal reflux (nGER) is common in patients with
      obstructive sleep apnea (OSA). Small, short-term studies have shown that
      treatment with nasal continuous positive airway pressure (CPAP) decreases
      esophageal acid exposure. OBJECTIVE: To examine the relationship between OSA and
      nGER, and the effect of CPAP on nGER, in a long-term follow-up study of a large
      cohort of patients with OSA and nGER. METHODS: We prospectively studied 331
      patients diagnosed as having OSA between October 1, 1993, and November 30, 2000.
      At baseline, patients graded their frequency of nGER symptoms on a scale of 1
      (never) to 5 (always). All patients were prescribed CPAP for their OSA. At follow
      up, the frequency of nGER symptoms was obtained by telephone interview. RESULTS:
      Of the 331 patients with OSA, nGER was present in 204 (62%) before treatment with
      CPAP. Follow-up was obtained in 181 patients (89%). Of these 181 patients, 165
      (91%) were still using CPAP and 16 (9%) were not, forming the treatment and
      control groups, respectively. The patients compliant with CPAP had a significant
      improvement in nGER score, from a mean of 3.38 before CPAP treatment to 1.75
      after treatment (48% improvement; P<.001), while patients not using CPAP (control
      subjects) showed no improvement (mean, 3.56 to 3.44; P =.55). There was a strong
      correlation between CPAP pressure and improvement in nGER score (correlation, r =
      0.70; P<.001), with patients with higher CPAP pressures demonstrating a greater
      improvement in nGER score. CONCLUSIONS: Nocturnal GER is common in patients with
      OSA. Treatment with nasal CPAP decreases the frequency of nGER symptoms by 48%.
      Higher nasal CPAP pressures are associated with greater improvement in nGER.

PMID- 12523916
TI  - Differences in breast cancer stage, treatment, and survival by race and
      ethnicity.
AB  - BACKGROUND: In the United States, black and Hispanic white women with breast
      cancer present with more advanced stages and have poorer survival rates than non
      Hispanic whites, whereas Asians and Pacific Islanders do not. However, Asians and
      Pacific Islanders and Hispanic whites are heterogeneous populations, and few
      studies have evaluated breast cancer stage, treatments, and mortality rates for
      subgroups of these populations. METHODS: Using data from 11 population-based
      tumor registries that participate in the Surveillance, Epidemiology, and End
      Results Program, we conducted a retrospective cohort study to evaluate the
      relationship between race and ethnicity and breast cancer stage, treatments, and
      mortality rates. The cohort of 124,934 women diagnosed as having a first primary
      invasive breast carcinoma between January 1, 1992, and December 31, 1998,
      included 97,999 non-Hispanic whites, 10,560 blacks, 322 American Indians, 8834
      Asians and Pacific Islanders, and 7219 Hispanic whites. RESULTS: Relative to non
      Hispanic whites, blacks, American Indians, Hawaiians, Indians and Pakistanis,
      Mexicans, South and Central Americans, and Puerto Ricans had 1.4- to 3.6-fold
      greater risks of presenting with stage IV breast cancer. Blacks, Mexicans, and
      Puerto Ricans were 20% to 50% more likely to receive or elect a first course of
      surgical and radiation treatment not meeting the 2000 National Comprehensive
      Cancer Network standards. In addition, blacks, American Indians, Hawaiians,
      Vietnamese, Mexicans, South and Central Americans, and Puerto Ricans had 20% to
      200% greater risks of mortality after a breast cancer diagnosis. CONCLUSIONS:
      Differences in breast cancer stage, treatments, and mortality rates are present
      by race and ethnicity. Breast cancer survival may be improved by targeting
      factors, particularly socioeconomic factors, that underlie these differences.

PMID- 12523917
TI  - Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal
      tract bleeding: a population-based cohort study.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been suspected
      of increasing the risk of bleeding. We examined the risk of upper
      gastrointestinal tract (GI) bleeding with use of antidepressant medication.
      METHODS: All users of antidepressants in the county of North Jutland, Denmark,
      from January 1, 1991, to December 31, 1995, were identified in the Pharmaco
      Epidemiologic Prescription Database of North Jutland. In the Hospital Discharge
      Register, hospitalizations for upper GI bleeding were searched among the 26 005
      users of antidepressant medications and compared with the number of
      hospitalizations in the population of North Jutland who did not receive
      prescriptions for antidepressants. RESULTS: During periods of SSRI use without
      use of other drugs associated with upper GI bleeding, we observed 55 upper GI
      bleeding episodes, which was 3.6 times more than expected (95% confidence
      interval, 2.7-4.7), corresponding to a rate difference of 3.1 per 1000 treatment
      years. Combined use of an SSRI and nonsteroidal anti-inflammatory drugs or low
      dose aspirin increased the risk to 12.2 (95% confidence interval, 7.1-19.5) and
      5.2 (95% confidence interval, 3.2-8.0), respectively. Non-SSRIs increased the
      risk of upper GI bleeding to 2.3 (95% confidence interval, 1.5-3.4), while
      antidepressants without action on the serotonin receptor had no significant
      effect on the risk of upper GI bleeding. The risk with SSRI use returned to unity
      after termination of SSRI use, while the risks were similarly increased during
      periods of use and nonuse of non-SSRIs. CONCLUSION: Selective serotonin reuptake
      inhibitors increase the risk of upper GI bleeding, and this effect is potentiated
      by concurrent use of nonsteroidal anti-inflammatory drugs or low-dose aspirin,
      whereas an increased risk of upper GI bleeding could not be attributed to other
      types of antidepressants.

PMID- 12523918
TI  - Long-term compliance with lipid-lowering medication after genetic screening for
      familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia is a common lipid disorder that
      predisposes to premature cardiovascular disease. Lipid-lowering treatment of
      affected individuals is widely advocated, and maximum benefit can be obtained if
      medication is started early. A screening program for familial
      hypercholesterolemia is ongoing in the Netherlands since 1994. To assess the
      extent of treatment and therapy compliance, patients were followed up for 2 years
      after the diagnosis was established. METHODS: Data were obtained by
      questionnaire. The 747 patients with familial hypercholesterolemia participating
      in the study were from the general community, and 62.4% were not receiving
      cholesterol-lowering medication. RESULTS: The overall percentage of treated
      patients had risen from 37.6% at screening to 92.5% 1 year later and then
      decreased to 85.9% 2 years after screening. During follow-up, 6.4% of patients
      discontinued their medication and 12.0% of untreated patients never started
      medication for various reasons, but in the majority of cases as advised by their
      own physicians. The mean reduction in low-density lipoprotein cholesterol levels
      in previously untreated patients was 30.1% (from 219 to 153 mg/dL [5.7 to 4.0
      mmol/L]). For those already receiving treatment, an additional reduction of 10.3%
      (from 195 to 175 mg/dL [5.0 to 4.5 mmol/L]) was obtained. CONCLUSIONS: Most
      patients were receiving treatment 2 years after identification and had a positive
      attitude toward the screening program. However, the reduction of cholesterol
      levels still did not meet the internationally accepted goals of treatment. This
      underscores the fact that additional education is required to improve the
      treatment of individuals with familial hypercholesterolemia.

PMID- 12523919
TI  - Association of younger age with poor glycemic control and obesity in urban
      african americans with type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus is highly prevalent in minority populations
      in the United States. We studied the relationship of age to glycemic control in a
      predominantly urban African American population with type 2 diabetes. METHODS: We
      selected all patients with type 2 diabetes who were enrolled in the Grady
      Diabetes Clinic, Atlanta, Ga, between April 1, 1991, and December 31, 1998, and
      had a hemoglobin A(1c) (HbA(1c)) level measured at their initial visit and at
      follow-up 5 to 12 months later (n = 2539). Patients were divided into 4 age
      categories: less than 30 years, 30 to 49 years, 50 to 69 years, and more than 69
      years old. We also studied the relationship of age to HbA(1c) level in a primary
      care clinic. RESULTS: At baseline, average HbA(1c) levels were 9.9%, 9.5%, 9.2%,
      and 8.8% in the 4 groups ranked in increasing age, respectively (P<.001), and
      body mass indexes (calculated as weight in kilograms divided by the square of
      height in meters) were 37.8, 33.9, 31.6, and 29.2, respectively (P<.001). On
      follow-up, HbA( 1c) level improved in all groups (P<.001), but there was still a
      trend for younger patients to have higher levels of HbA(1c). There was little
      change in body mass index with time. Younger age, longer diabetes duration,
      higher body mass index, less frequent interval visits, and treatment with oral
      agents or insulin were associated with a higher HbA(1c) level at follow-up. Our
      findings in a primary care clinic showed also that HbA( 1c) level and body mass
      index were negatively correlated with age (P<.001). CONCLUSION: Our data show a
      high prevalence of obesity and poor glycemic control in young adult urban African
      Americans with diabetes.

PMID- 12523920
TI  - Acyclovir-resistant genital herpes among persons attending sexually transmitted
      disease and human immunodeficiency virus clinics.
AB  - BACKGROUND: Genital herpes is epidemic in the United States; long-term acyclovir
      therapy is common; and long-term use of antimicrobials in suppressive doses
      favors development of resistance. OBJECTIVE: To determine the prevalence of and
      risk factors for acyclovir-resistant genital herpes. METHODS: We identified and
      attempted to enroll all patients 18 years or older with suspected genital herpes
      who attended 22 sexually transmitted disease and human immunodeficiency virus
      (HIV) clinics in the United States between October 1996 and April 1998. We
      conducted standardized interviews of all consenting patients. Lesions were
      cultured, and isolates were typed as herpes simplex virus (HSV) 1 or HSV-2 and
      tested for acyclovir sensitivity (using a 50% inhibitory concentration of 2
      microg/mL) by plaque reduction, which was independently confirmed. RESULTS:
      Herpes simplex virus was isolated from 2088 of 3602 patients, and 90.2% of
      isolates were HSV-2. Fifteen isolates, all HSV-2, were acyclovir resistant. Three
      (0.18%) of 1644 HIV-negative patients had acyclovir-resistant isolates (95%
      confidence interval [CI], 0.04%-0.5%); resistance was associated with oral
      (P<.006) and topical (P<.001) acyclovir use. Twelve (5.3%) of 226 HIV-positive
      patients yielded resistant HSV isolates (95% CI, 2.8%-9.1%); resistance was
      associated with oral acyclovir use (P<.001), duration of the current episode
      (P<.001), history of recurrent genital herpes (P<.01), and low CD4 cell count
      (P<.05). CONCLUSIONS: In the 15 years following licensure of acyclovir,
      resistance to the drug remains low among immunocompetent patients. However, 5% of
      HIV-positive patients had resistant HSV-2 isolates. Continued surveillance is
      essential to monitor changes in acyclovir resistance and to characterize the
      clinical and public health importance of acyclovir-resistant HSV.

PMID- 12523921
TI  - Closing the loop: physician communication with diabetic patients who have low
      health literacy.
AB  - BACKGROUND: Patients recall or comprehend as little as half of what physicians
      convey during an outpatient encounter. To enhance recall, comprehension, and
      adherence, it is recommended that physicians elicit patients' comprehension of
      new concepts and tailor subsequent information, particularly for patients with
      low functional health literacy. It is not known how frequently physicians apply
      this interactive educational strategy, or whether it is associated with improved
      health outcomes. METHODS: We used direct observation to measure the extent to
      which primary care physicians working in a public hospital assess patient recall
      and comprehension of new concepts during outpatient encounters, using audiotapes
      of visits between 38 physicians and 74 English-speaking patients with diabetes
      mellitus and low functional health literacy. We then examined whether there was
      an association between physicians' application of this interactive communication
      strategy and patients' glycemic control using information from clinical and
      administrative databases. RESULTS: Physicians assessed recall and comprehension
      of any new concept in 12 (20%) of 61 visits and for 15 (12%) of 124 new concepts.
      Patients whose physicians assessed recall or comprehension were more likely to
      have hemoglobin A(1c) levels below the mean (< or = 8.6%) vs patients whose
      physicians did not (odds ratio, 8.96; 95% confidence interval, 1.1-74.9) (P
      =.02). After multivariate logistic regression, the 2 variables independently
      associated with good glycemic control were higher health literacy levels (odds
      ratio, 3.97; 95% confidence interval, 1.09-14.47) (P =.04) and physicians'
      application of the interactive communication strategy (odds ratio, 15.15; 95%
      confidence interval, 2.07-110.78) (P<.01). CONCLUSIONS: Primary care physicians
      caring for patients with diabetes mellitus and low functional health literacy
      rarely assessed patient recall or comprehension of new concepts. Overlooking this
      step in communication reflects a missed opportunity that may have important
      clinical implications.

PMID- 12523922
TI  - C-reactive protein as a predictor for incident diabetes mellitus among middle
      aged men: results from the MONICA Augsburg cohort study, 1984-1998.
AB  - BACKGROUND: Previous studies have suggested that low-grade systemic inflammation
      is involved in the pathogenesis of type 2 diabetes mellitus. OBJECTIVE: To
      investigate the association between C-reactive protein (CRP), the classic acute
      phase protein, and incident type 2 diabetes mellitus among middle-aged men.
      METHODS: A total of 2052 initially nondiabetic men aged 45 to 74 years who
      participated in 1 of the 3 MONICA (Monitoring of Trends and Determinants in
      Cardiovascular Disease) Augsburg surveys between 1984 and 1995 were followed up
      for an average of 7.2 years. Incidence of diabetes was assessed by questionnaire
      mailed to participants in 1998. High-sensitive CRP was measured by an
      immunoradiometric assay. RESULTS: A total of 101 cases of incident diabetes
      occurred during the follow-up period. The age-standardized incidence rate was 6.9
      per 1000 person-years. Men with CRP levels in the highest quartile (CRP > or =
      2.91 mg/L) had a 2.7 times higher risk of developing diabetes (95% confidence
      interval, 1.4-5.2) compared with men in the lowest quartile (CRP < or = 0.67
      mg/L) in a Cox proportional hazards model adjusted for age and survey. After
      further adjustment for body mass index, smoking, and systolic blood pressure, the
      observed association was significantly reduced and became nonsignificant.
      CONCLUSIONS: Low-grade systemic inflammation is associated with an increased risk
      of type 2 diabetes mellitus in middle-aged men. Inflammation could be one
      mechanism by which known risk factors for diabetes mellitus, such as obesity,
      smoking, and hypertension, promote the development of diabetes mellitus.

PMID- 12523923
TI  - Relationship between avoidable hospitalizations for diabetes mellitus and income
      level.
AB  - BACKGROUND: Acute diabetic emergencies are potentially avoidable or amenable to
      timely and effective outpatient therapy. OBJECTIVE: To evaluate the relationship
      between socioeconomic status (SES) and acute complications of diabetes mellitus
      in Ontario. METHODS: We used a population-based cohort of persons with diabetes
      mellitus (N = 605 825) derived from hospital and physician service claims between
      April 1, 1992, and March 31, 1999. Socioeconomic status was estimated using
      neighborhood-level data from the 1996 Canadian Census. Outcome events were
      defined as 1 or more hospitalizations or emergency department visits for
      hyperglycemia or hypoglycemia. RESULTS: There was a clear inverse gradient
      between income level and event rates. Individuals in the lowest income quintile
      were 44% more likely to have an event than those in the highest quintile (16.4%
      vs 11.4%; P<.001) and had a greater propensity toward recurrent emergency
      department admissions (1.9 vs 1.6 episodes per patient; P<.001). The gradient was
      most marked in 45- to 64-year-olds (odds ratio [OR], 1.76; 95% confidence
      interval [CI], 1.69-1.82) and less apparent in children (OR, 1.06; 95% CI, 0.99
      1.13). The relationship between SES and events persisted after adjusting for age,
      sex, urban vs rural residence, comorbidity, frequency of physician visits,
      continuity of care, physician specialty, and geographic region (adjusted OR, 1.09
      [95% CI, 1.08-1.10] per quintile level). In contrast, admission rates for non
      ambulatory care-sensitive conditions (appendicitis and hip fracture) were
      unaffected by SES. CONCLUSION: Even when some economic barriers to accessing care
      are removed, patients from low-SES neighborhoods still experience an excess
      number of hospitalizations for conditions that should be prevented by optimal
      care in the ambulatory setting.

PMID- 12523924
TI  - Frequency and impact of active clinical issues and new impairments on hospital
      discharge in patients with hip fracture.
AB  - BACKGROUND: Hip fracture is associated with significant mortality and disability.
      Patients who are discharged from the hospital with active clinical problems may
      have worse outcomes than those patients without active clinical problems.
      OBJECTIVE: To assess the frequency and impact of clinical problems at discharge
      on clinical and functional hip fracture outcomes. METHODS: Detailed clinical data
      were collected from 559 patients in a prospective, multicenter observational
      cohort study. Active clinical issues (ACIs) on discharge included the following:
      temperature of 38.3 degrees C or higher, heart rate of more than 100/min or less
      than 60/min, systolic blood pressure higher than 180 mm Hg or lower than 90 mm
      Hg, diastolic blood pressure higher than 110 mm Hg or lower than 60 mm Hg,
      respiratory rate of more than 24/min, oxygen saturation of less than 90%, altered
      mental status, no oral intake, shortness of breath, chest pain, arrhythmias, or
      wound infection. New impairments (NIs) included bowel and bladder incontinence,
      inability to get out of bed, and decubitus ulcer. Outcomes were deaths,
      readmissions, and functional mobility 60 days after discharge. RESULTS: Overall,
      94 patients (16.8%) had 1 or more ACIs, and 229 (41.0%) had 1 or more NIs on
      discharge. Both ACIs and NIs on discharge were associated with increased risk
      adjusted rates of death (odds ratio, 1.8; 95% confidence interval, 1.2-2.8) or
      readmission (odds ratio, 1.7; 95% confidence interval, 1.2-2.3). The NIs on
      discharge were also associated with worse functional mobility (P<.004). These
      relationships persisted in multivariate analyses that controlled for a previously
      validated, hip fracture-specific risk adjustment measure. CONCLUSIONS: Clinicians
      should consider information about ACIs and NIs when deciding readiness for
      discharge and planning post-acute care.

PMID- 12523925
TI  - Celecoxib-related renal papillary necrosis.
AB  - Selective cyclooxygenase 2 (COX-2) inhibitors are known to affect renal
      prostaglandins (epoprostenol and dinoprostone), which are at least in part COX-2
      dependent. Consequently, adverse events including hypertension, peripheral edema,
      hypercalemia, hyponatremia, and acute renal failure have been reported to occur
      with the new COX-2-specific inhibitors. This case report posits celecoxib as a
      likely cause of renal papillary necrosis and alerts physicians to the possibility
      of this additional renal complication with COX-2-specific inhibitors.

PMID- 12523926
TI  - Ethacrynic acid and the sulfa-sensitive patient.

PMID- 12523927
TI  - Misleading report of massive bleeding in a patient taking pentosan polysulfate.

PMID- 12523929
TI  - Immune thrombocytopenic purpura and Helicobacter pylori infection.

PMID- 12523931
TI  - Prognostic value of systolic and diastolic blood pressure in treated hypertensive
      men: clarification.

PMID- 12523932
TI  - Elderly asthmatic patients.

PMID- 12523934
TI  - Saccharomyces cerevisiae contains a Type II phosphoinositide 4-kinase.
AB  - The yeast Saccharomyces cerevisiae contains two known phosphoinositide 4-kinases
      (PI 4-kinases), which are encoded by PIK1 and STT4; both are essential. Pik1p is
      important for exocytic transport from the Golgi, whereas Stt4p plays a role in
      cell-wall integrity and cytoskeletal rearrangements. In the present study, we
      report that cells have a third PI 4-kinase activity encoded by LSB6, a protein
      identified previously in a two-hybrid screen as interacting with LAS17p. Although
      Pik1p and Stt4p are closely related members of the Type III class of PI 4
      kinases, Lsb6p belongs to the distinct Type II class, based on its amino acid
      sequence, its sensitivity to inhibition by adenosine and its insensitivity to
      wortmannin. Lsb6p is the first fungal Type II enzyme cloned. The protein was
      expressed and purified from Sf9 cells and used to define kinetic parameters. As
      commonly observed for surface-active enzymes, activities varied both with
      substrate concentration and lipid/detergent molar ratios. Maximal activities of
      approx. 100 min(-1) were obtained at the PI/Triton X-100 ratio of 1:5. The K (m)
      value for ATP was 266 microM, intermediate between the values reported for
      mammalian Type II and III kinases. Epitope-tagged protein, expressed in yeast,
      was entirely particulate, and about half of it could be extracted with non-ionic
      detergent. Lsb6p-green fluorescent protein was found both on vacuolar membranes
      and on the plasma membrane, suggesting a role in endocytic or exocytic pathways.

PMID- 12523935
TI  - Cystic fibrosis transmembrane conductance regulator: the NBF1+R (nucleotide
      binding fold 1 and regulatory domain) segment acting alone catalyses a
      Co2+/Mn2+/Mg2+-ATPase activity markedly inhibited by both Cd2+ and the transition
      state analogue orthovanadate.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene encoding CFTR (cystic
      fibrosis transmembrane conductance regulator), a regulated anion channel and
      member of the ATP-binding-cassette transporter (ABC transporter) superfamily. Of
      CFTR's five domains, the first nucleotide-binding fold (NBF1) has been of
      greatest interest both because it is the major 'hotspot' for mutations that cause
      CF, and because it is connected to a unique regulatory domain (R). However,
      attempts have failed to obtain a catalytically active NBF1+R protein in the
      absence of a fusion partner. Here, we report that such a protein can be obtained
      following its overexpression in bacteria. The pure NBF1+R protein exhibits
      significant ATPase activity [catalytic-centre activity (turnover number) 6.7 min(
      1)] and an apparent affinity for ATP ( K (m), 8.7 microM) higher than reported
      previously for CFTR or segments thereof. As predicted, the ATPase activity is
      inhibited by mutations in the Walker A motif. It is also inhibited by vanadate, a
      transition-state analogue. Surprisingly, however, the best divalent metal
      activator is Co(2+), followed by Mn(2+) and Mg(2+). In contrast, Ca(2+) is
      ineffective and Cd(2+) is a potent inhibitor. These novel studies, while
      demonstrating clearly that CFTR's NBF1+R segment can act independently as an
      active, vanadate-sensitive ATPase, also identify its unique cation activators and
      a new inhibitor, thus providing insight into the nature of its active site.

PMID- 12523936
TI  - Steroid and bile acid conjugates are substrates of human multidrug-resistance
      protein (MRP) 4 (ATP-binding cassette C4).
AB  - Human multidrug-resistance protein (MRP) 4 transports cyclic nucleotides and when
      overproduced in mammalian cells mediates resistance to some nucleoside analogues.
      Recently, it has been shown that Mrp4 is induced in the livers of Fxr ((-/-))
      mice, which have increased levels of serum bile acids. Since MRP4, like MRP1-3,
      also mediates transport of a model steroid conjugate substrate, oestradiol 17
      beta-D-glucuronide (E(2)17betaG), we tested whether MRP4 may be involved in the
      transport of steroid and bile acid conjugates. Bile salts, especially sulphated
      derivatives, and cholestatic oestrogens inhibited the MRP4-mediated transport of
      E(2)17betaG. Inhibition by oestradiol 3,17-disulphate and taurolithocholate 3
      sulphate was competitive, suggesting that these compounds are MRP4 substrates.
      Furthermore, we found that MRP4 transports dehydroepiandrosterone 3-sulphate
      (DHEAS), the most abundant circulating steroid in humans, which is made in the
      adrenal gland. The ATP-dependent transport of DHEAS by MRP4 showed saturable
      kinetics with K (m) and V (max) values of 2 microM and 45 pmol/mg per min,
      respectively (at 27 degrees C). We further studied the possible involvement of
      other members of the MRP family of transporters in the transport of DHEAS. We
      found that MRP1 transports DHEAS in a glutathione-dependent manner and exhibits K
      (m) and V (max) values of 5 microM and 73 pmol/mg per min, respectively (at 27
      degrees C). No transport of DHEAS was observed in membrane vesicles containing
      MRP2 or MRP3. Our findings suggest a physiological role for MRP1 and MRP4 in
      DHEAS transport and an involvement of MRP4 in transport of conjugated steroids
      and bile acids.

PMID- 12523937
TI  - The modular architecture of Cellvibrio japonicus mannanases in glycoside
      hydrolase families 5 and 26 points to differences in their role in mannan
      degradation.
AB  - beta-1,4-Mannanases (mannanases), which hydrolyse mannans and glucomannans, are
      located in glycoside hydrolase families (GHs) 5 and 26. To investigate whether
      there are fundamental differences in the molecular architecture and biochemical
      properties of GH5 and GH26 mannanases, four genes encoding these enzymes were
      isolated from Cellvibrio japonicus and the encoded glycoside hydrolases were
      characterized. The four genes, man5A, man5B, man5C and man26B, encode the
      mannanases Man5A, Man5B, Man5C and Man26B, respectively. Man26B consists of an N
      terminal signal peptide linked via an extended serine-rich region to a GH26
      catalytic domain. Man5A, Man5B and Man5C contain GH5 catalytic domains and non
      catalytic carbohydrate-binding modules (CBMs) belonging to families 2a, 5 and 10;
      Man5C in addition contains a module defined as X4 of unknown function. The family
      10 and 2a CBMs bound to crystalline cellulose and ivory nut crystalline mannan,
      displaying very similar properties to the corresponding family 10 and 2a CBMs
      from Cellvibrio cellulases and xylanases. CBM5 bound weakly to these crystalline
      polysaccharides. The catalytic domains of Man5A, Man5B and Man26B hydrolysed
      galactomannan and glucomannan, but displayed no activity against crystalline
      mannan or cellulosic substrates. Although Man5C was less active against
      glucomannan and galactomannan than the other mannanases, it did attack
      crystalline ivory nut mannan. All the enzymes exhibited classic endo-activity
      producing a mixture of oligosaccharides during the initial phase of the reaction,
      although their mode of action against manno-oligosaccharides and glucomannan
      indicated differences in the topology of the respective substrate-binding sites.
      This report points to a different role for GH5 and GH26 mannanases from C.
      japonicus. We propose that as the GH5 enzymes contain CBMs that bind crystalline
      polysaccharides, these enzymes are likely to target mannans that are integral to
      the plant cell wall, while GH26 mannanases, which lack CBMs and rapidly release
      mannose from polysaccharides and oligosaccharides, target the storage
      polysaccharide galactomannan and manno-oligosaccharides.

PMID- 12523938
TI  - 1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant
      generation: role of transferrin-receptor-dependent iron and hydrogen peroxide.
AB  - 1-Methyl-4-phenylpyridinium (MPP(+)) is a neurotoxin used in cellular models of
      Parkinson's Disease. Although intracellular iron plays a crucial role in MPP(+)
      induced apoptosis, the molecular signalling mechanisms linking iron, reactive
      oxygen species (ROS) and apoptosis are still unknown. We investigated these
      aspects using cerebellar granule neurons (CGNs) and human SH-SY5Y neuroblastoma
      cells. MPP(+) enhanced caspase 3 activity after 24 h with significant increases
      as early as 12 h after treatment of cells. Pre-treatment of CGNs and
      neuroblastoma cells with the metalloporphyrin antioxidant enzyme mimic,
      Fe(III)tetrakis(4-benzoic acid)porphyrin (FeTBAP), completely prevented the
      MPP(+)-induced caspase 3 activity as did overexpression of glutathione peroxidase
      (GPx1) and pre-treatment with a lipophilic, cell-permeable iron chelator [N, N '
      bis-(2-hydroxybenzyl)ethylenediamine-N, N '-diacetic acid, HBED]. MPP(+)
      treatment increased the number of TUNEL (terminal deoxynucleotidyl transferase
      mediated dUTP nick-end-labelling)-positive cells which was completely blocked by
      pre-treatment with FeTBAP. MPP(+) treatment significantly decreased the aconitase
      and mitochondrial complex I activities; pre-treatment with FeTBAP, HBED and GPx1
      overexpression reversed this effect. MPP(+) treatment increased the intracellular
      oxidative stress by 2-3-fold, as determined by oxidation of
      dichlorodihydrofluorescein and dihydroethidium (hydroethidine). These effects
      were reversed by pre-treatment of cells with FeTBAP and HBED and by GPx1
      overexpression. MPP(+)-treatment enhanced the cell-surface transferrin receptor
      (TfR) expression, suggesting a role for TfR-induced iron uptake in MPP(+)
      toxicity. Treatment of cells with anti-TfR antibody (IgA class) inhibited MPP(+)
      induced caspase activation. Inhibition of nitric oxide synthase activity did not
      affect caspase 3 activity, apoptotic cell death or ROS generation by MPP(+).
      Overall, these results suggest that MPP(+)-induced cell death in CGNs and
      neuroblastoma cells proceeds via apoptosis and involves mitochondrial release of
      ROS and TfR-dependent iron.

PMID- 12523939
TI  - Toward estimating the impact of changes in immigrants' insurance eligibility on
      hospital expenditures for uncompensated care.
AB  - BACKGROUND: The Personal Responsibility and Work Opportunity Reconciliation Act
      (PRWORA) of 1996 gave states the option to withdraw Medicaid coverage of
      nonemergency care from most legal immigrants. Our goal was to assess the effect
      of PRWORA on hospital uncompensated care in the United States. METHODS: We
      collected the following state-level data for the period from 1994 through 1999:
      foreign-born, noncitizen population and health uninsurance rates (US Census
      Current Population Survey); percentage of teaching hospitals (American Hospital
      Association Annual Survey of Hospitals); and each state's decision whether to
      implement the PRWORA Medicaid bar for legal permanent residents or to continue
      offering nonemergency Medicaid coverage using state-only funds (Urban Institute).
      We modeled uncompensated care expenditures by state (also from the Annual Survey
      of Hospitals) in both univariate and multivariable regression analyses. RESULTS:
      When measured at the state level, there was no significant relationship between
      uncompensated care expenditures and states' percentage of noncitizen immigrants.
      Uninsurance rates were the only significant factor in predicting uncompensated
      hospital care expenditures by state. CONCLUSIONS: Reducing the number of
      uninsured patients would most surely reduce hospital expenditures for
      uncompensated care. However, data limitations hampered our efforts to obtain a
      monetary estimate of hospitals' financial losses due specifically to the
      immigrant eligibility changes in PRWORA. Quantifying the impact of these
      provisions on hospitals will require better data sources.

PMID- 12523940
TI  - The study of reproductive outcome and the health of offspring of UK veterans of
      the Gulf war: methods and description of the study population.
AB  - BACKGROUND: The aim of this study is to determine whether Gulf war veterans and
      their partners are at increased risk of adverse reproductive events and whether
      their children have increased risk of serious health problems. Methods and
      response to the study are reported here. METHODS: This was a retrospective cohort
      study of reproduction among UK Gulf war veterans, with a comparison cohort of
      Armed Service personnel who were not deployed to the Gulf. Reproductive history
      and details of children's health was collected by means of a validated postal
      questionnaire. A separate study of non-responders was conducted. RESULTS:
      Questionnaires were returned by a total of 25,084 Gulf war veterans (24,379 men)
      and 19,003 (18,439 men) subjects in the comparison group. After adjusting for
      undelivered mail the response rate was 53% for Gulf war veterans and 42% for non
      Gulf veterans among men, 72% and 60% among women. Data from the non-responder
      study suggests that failure to respond to the main survey was largely unrelated
      to reproduction. 11,155 (46%) male Gulf war veterans and 7,769 (42%) male non
      Gulf war veterans had conceived, or attempted to conceive, since the Gulf war.
      They reported 16442 and 11517 pregnancies respectively in that period. For women,
      313 (44%) Gulf veterans and 235 (42%) non-Gulf veterans reported 484 and 377
      pregnancies respectively conceived since the Gulf war. CONCLUSIONS: This survey
      enabled collection of information on a range of reproductive outcomes from
      veterans of the Gulf war and a suitably matched comparison cohort. Although the
      response rate for men was disappointing, selection bias related to reproduction
      does not appear to be strong in these data.

PMID- 12523941
TI  - Contextual factors influencing the eating behaviours of African American women: a
      focus group investigation.
AB  - OBJECTIVES: African American women suffer disproportionately from many chronic
      diseases, and it is well acknowledged that eating patterns and habits are
      important contributory factors. Our goal was to describe and understand how
      personal and contextual factors among African American women contribute to food
      choices that increase the risk for chronic disease. DESIGN: Focus groups were
      conducted with 40 African American women. Two experimenters abstracted and
      categorized statements about eating attitudes, beliefs and behaviours from the
      focus group transcripts. RESULTS: A total of 139 statements were sorted into 10
      major categories: (1). specific meals, (2). planning, (3). family/social, (4).
      snacking, (5). food preferences, (6). health awareness, (7). shopping, (8). food
      preparation, (9). eating out and (10). emotional. These categories were
      subdivided into 49 sub-categories to reveal more specific patterns of behaviour.
      CONCLUSION: African American women showed considerable variability in how they
      approached planning, choosing, preparing and eating food. A plethora of habits
      and food meanings-influenced by the personal, cultural, and environmental context
      place these women at high risk for chronic disease. There were attempts to eat
      'healthy', but these were overcome by traditions, social influences, habits and
      price. Individualized assessments to determine how each woman uses contextual
      information to make her food choices should be conducted in order to facilitate
      permanent eating behaviour change.

PMID- 12523942
TI  - Choice of food and food traditions in pre-war Bosnia-Herzegovina: focus group
      interviews with immigrant women in Sweden.
AB  - OBJECTIVES: Immigrants in Sweden have on average poorer health than native
      Swedes, including the risk of nutritional problems. In Sweden's multicultural
      society there is a need for increased knowledge about eating habits in public
      health work within health and education. A survey of refugees from Bosnia
      Herzegovina living in Sweden was undertaken to describe the choice of food and
      food traditions in pre-war Bosnia. The purpose was to introduce the subject of
      food, health and migration into public health work and develop culture-adapted
      food and health advice. DESIGN: Focus-group interviews were undertaken with a
      total of 20 women refugees from Bosnia-Herzegovina. RESULTS: Qualitative data
      analysis identified a large consumption of bread as a staple food with meat,
      vegetables, milk, cheese, legumes, egg and fish as additions. Self-sufficiency
      was noted with milk souring, jam making and the production of sweet fruit drinks.
      Home made cheese and drying or smoking of meat were common methods of food
      storage. In child rearing, breast-feeding for 6-8 months was most common. Home
      made breast milk replacements were made from semolina, rice and 'petit biscuits'.
      CONCLUSION: Several important factors need to be taken into account when giving
      culturally adapted food and health advice to Bosnian families, such as
      encouraging bread, vegetable and legume consumption and giving advice on
      substituting sweet fruit drinks for natural fruit. One should be conscious of how
      religious beliefs as well as socio-cultural, historical, ecological, economical
      and psychological influences may guide food choices.

PMID- 12523943
TI  - The North Norwegian Youth Study: cigarette smoking among ethnically diverse
      adolescents.
AB  - OBJECTIVES: To examine ethnic and gender differences in the prevalence of
      cigarette smoking among indigenous Sami, ethnocultural Kven and majority
      Norwegian adolescents, and ethnic-specific gender differences in smoking. DESIGN:
      'The North Norwegian Youth Study' was a longitudinal epidemiological study. It
      collected data at two time points at a three-year interval (1994/95 and 1997/98).
      It was based on student self-reports (10-12th grade) from 21 state schools in
      North Norway. The initial analysis included 2997 students aged 15-19 years
      (response rate (RR): 85%) and 1533 responders at follow-up (RR: 55%). The sample
      consisted of 12% Kvens, 23% Sami and 65% Norwegians. RESULTS: Baseline (follow
      up) smoking rates were; 38% (35%) never smokers, 29% (29%) current regular
      smokers, 11% (12%) current irregular smokers and 23% (24%) former smokers. Ethnic
      differences in cigarette smoking were minor and found at baseline only. Sami
      students reported a lower proportion of current irregular smokers (8%) and a
      higher rate of former smokers (26%). Gender differences were most pronounced at
      baseline with females more involved in cigarette smoking than their male peers.
      However, males were more likely to be heavy smokers at both time points.
      CONCLUSIONS: Cigarette smoking among adolescents and young people in North Norway
      was generally independent of the ethnicity of the respondents. There were no
      ethnic differences in smoking rates at follow-up. Sami youth were not at higher
      risk of cigarette smoking than their non-indigenous peers. This finding contrasts
      with findings among other Arctic indigenous youth.

PMID- 12523944
TI  - Behavioural risk factors and protective factors in adolescents: a comparison of
      Latinos and non-Latino whites.
AB  - OBJECTIVES: This study investigated differences in behavioural health protective
      and risk factors in US Latino and non-Latino White adolescents as well as
      differences among Latinos with different levels of acculturation using a
      bicultural acculturation model. The bicultural model is consistent with current
      understanding of cultural change processes; however it has infrequently been
      applied to understand adolescent health outcomes. The outcomes included risk and
      health behaviours as well as mental health factors consistent with Jessor's
      framework for describing adolescents' health status. DESIGN: Participants
      included 1119 students randomly selected from all middle schools of a Northern
      California district. Respondents completed project staff administered self
      reports surveys in their schools that included assessments of health behaviours,
      mental health, and socio-cultural variables-including acculturation level.
      RESULTS: Latinos were at higher risk than non-Latino Whites in the following
      areas: academic orientation, physical activity, and sunscreen use. Boys and those
      of lower social class were more likely to report use of various substances and
      violence. Among Latinos, those in the marginalised acculturation group-those with
      less attachments and adaptations to Latino and other cultures, showed less
      desirable mental health outcomes than the bicultural group. CONCLUSION: These
      results extend prior research by assessing the health needs of early adolescent
      youth. The study found important differences within Latinos using a bicultural
      acculturation model. The use of a bicultural acculturation model, or cultural
      orientation approach more generally, may have special utility for addressing
      health issues wherever minority populations interact with a dominant society.

PMID- 12523946
TI  - Exploration of factors linked with high cervical cancer rates in women from the
      former Yugoslavia in Victoria, Australia.
AB  - OBJECTIVES: The aim of the project was to identify the cervical screening rate
      and other factors that may be associated with high rates of cervical cancer in
      women from the former Yugoslavia compared to the general population in Victoria,
      Australia. DESIGN: A cross-sectional survey was conducted by structured personal
      interviews of 42 Bosnian, 56 Croatian, 49 Macedonian, and 35 Serbian women, and
      39 women who identified as Yugoslav or of mixed background. Self-report data were
      collected on Pap testing behaviour, estimated screening rate of each community,
      stage-based barriers to cervical screening, and women's theories about causes of
      cervical cancer within their community. RESULTS: Women in this study had an
      acceptable screening rate, but barriers to cervical screening were similar to
      those of other groups. While Macedonian women believed more of their community
      had Pap tests than the other cultural groups, just under half were under-screened
      themselves. Smoking rates were very high for women in this study. The most common
      causes of cervical cancer suggested by women in the study were: a low screening
      rate, lifestyle stress, and chemicals. CONCLUSION: It is unlikely that the high
      cervical cancer rate in women from the former Yugoslavia is a result of under
      screening, lifestyle stress, or chemicals. Smoking may well contribute to the
      cancer rate, however the most likely explanation is that cancers not previously
      detected in Yugoslavia are now being found, together with cervical abnormalities,
      within the systematic two yearly screening programme of PapScreen Victoria, in
      Australia.

PMID- 12523945
TI  - Ethnic differences in self-reported lack of access to a regular doctor: a
      population-based study.
AB  - OBJECTIVE: The aim of this study was to investigate ethnic differences in self
      reported lack of access to a regular doctor in Malmo, Sweden. DESIGN: The public
      health survey in Malmo 1994 was a cross sectional population study. Data were
      collected from 5600 people aged 20-80 years using a postal questionnaire. The
      participation rate was 71%. The population was categorised according to country
      of birth: born in Sweden, other Nordic countries, other Western countries,
      Yugoslavia, Eastern Europe, Arabic speaking countries and other countries.
      Multivariate logistic regression analysis was performed in order to investigate
      the importance of possible confounders on the differences by country of origin in
      lack of access to a regular doctor. RESULTS: A 56.3% proportion of all men and
      48.8% of all women lacked access to a regular doctor. The odds ratios of lacking
      access were significantly higher among men born in Nordic countries, Arabic
      countries and other countries compared to men born in Sweden but disappeared
      after adjustment for age. The same patterns were observed for women born in
      Eastern Europe, Arabic countries and other countries compared to women born in
      Sweden, and remained after adjustment for age. In the multivariate analysis
      including age, education, ability to pay bills every month and self-reported
      health, no significant differences in lack of access to a regular doctor remained
      among men, while the odds ratios were significantly lower among women born in
      other Western countries, but still significantly higher among women born in
      Arabic speaking countries and all other countries. CONCLUSION: Self-reported lack
      of access to a regular doctor was significantly higher among men born in Nordic
      countries, Arabic countries and other countries compared to men born in Sweden,
      but all these differences disappeared after adjument for age and in the
      multivariate analysis. Women born in Arabic speaking countries and other
      countries lacked access to a regular doctor to a significantly higher extent
      compared with women born in Sweden, and these differences remained in the
      multivariate analysis.

PMID- 12523947
TI  - Reflex sympathetic dystrophy--a complex regional pain syndrome.
AB  - Reflex sympathetic dystrophy (RSD) is a complex and poorly-understood condition
      characterized by: (a) pain and altered sensation; (b) motor disturbance and soft
      tissue change; (c) vasomotor and autonomic changes; and (d) psychosocial
      disturbance. Neurological symptoms typically do not conform to any particular
      pattern of nerve damage. Many different names have been ascribed to this
      condition and most recently the term 'complex regional pain syndrome' has been
      coined to emphasize the complex interaction of somatic, psychological and
      behavioural factors. Diagnostic criteria have been proposed by the International
      Association for the Study of Pain, but are still subject to debate. This review
      article describes the clinical features which may present as part of the
      condition, and the patho-physiology and pre-disposing factors so far identified.
      The evidence for effectiveness of different interventions is presented and a
      treatment approach outlined for inter-disciplinary management. While RSD is
      traditionally associated with pain in the extremities, the possibility is raised
      that the same process may underlie chronic pain syndromes affecting more central
      structures, such as testicular or pelvic pain.

PMID- 12523948
TI  - Self-responsibility and coping with pain: disparate attitudes toward psychosocial
      issues in recovery from work place injury.
AB  - PURPOSE: To compare injured worker and health professional ratings of
      psychosocial variables as they relate to recovery. METHOD: Seventy patients and
      70 health care staff at an injured worker rehabilitation centre completed a 17
      item checklist. Each subject selected five psychosocial variables believed to be
      most important to recovery. Group ratings were compared using chi-square with a
      Bonferroni adjustment. RESULTS: In general, patients and health professionals
      agreed on the relative importance of 15 of 17 variables. However, the groups did
      differ significantly on two items--staff rated 'self-responsibility' higher than
      patients, while patients rated 'coping with pain' higher than staff. CONCLUSIONS:
      The ratings reflect the occasionally divergent goals and expectations of the
      rehabilitation staff and patient groups. Consequently, some patients may be moved
      into inappropriate treatment modalities, resulting in non-compliance. Being aware
      of patient beliefs and expectations should assist health care professionals in
      generating improved rehabilitation outcomes by promoting better co-operation
      through shared perceptions and goals.

PMID- 12523949
TI  - Physicians' preferences and expectations in stroke rehabilitation--results of a
      case-based questionnaire survey.
AB  - PURPOSE: Analysis of medical decisions in the differential allocation of stroke
      rehabilitation programmes. METHOD: Medical specialists routinely involved in the
      treatment and rehabilitation of stroke patients from acute hospitals,
      rehabilitation centres, and the Medical Services of the Workers' Pension Funds of
      Sachsen-Anhalt and Mecklenburg-Vorpommern were included in a systematic survey,
      in which they had to give their opinions on the individually optimal
      rehabilitation setting and therapies and probable outcome on the basis of case
      vignettes. These specialists are crucial for decision-making in rehabilitation
      resource allocation. RESULTS: Both allocation and prognosis did not depend only
      on patient but also on physician characteristics. Neurologists tended to prefer
      outpatient rehabilitation and expected a greater effect of rehabilitation upon
      ADL-function than specialists from other professions. Preferred rehabilitation
      setting did not influence the physicians' subjective prognosis. For patients who
      qualified both for in- and outpatient rehabilitation, the two settings,
      therapeutic potentials were considered to be equivalent. CONCLUSIONS: Differences
      in setting and treatment preferences between experts concerning optimal treatment
      cannot be resolved on the basis of available evidence. Further data are required
      that allow to decide which type of rehabilitation is best suited for a given
      patient.

PMID- 12523950
TI  - Changes in upper limb joint torque patterns and EMG signals with fatigue
      following a stroke.
AB  - PURPOSE: Little is known concerning changes in neuromuscular fatigue following a
      stroke. The purpose of this study was to evaluate the effect of a stroke on
      fatigue-related changes in upper limb torque patterns and electromyographic
      signals. METHOD: The paretic and non-paretic upper limb of 10 adults (51-79
      years) who had a stroke (time since stroke: 3-75 months) were compared. Subjects
      had to perform a fatigue task consisting of a sustained maximal isometric
      contraction in elbow flexion until torque decreased to below 50% of initial. The
      main variables of interest assessed before, during and after fatigue were: (1)
      the torque in elbow flexion, as well as associated forces/torques at the shoulder
      and forearm; (2) the level of voluntary activation; (3) the amplitude (RMS); and
      (4) frequency content (median frequency) of electromyographic signals. RESULTS:
      Compared to the non-paretic side, the paretic side showed a lower level of
      voluntary activation and higher relative torque levels at the forearm and
      shoulder which could both be exaggerated with fatigue, and a lesser fatigue
      related decrease in median frequency. CONCLUSIONS: Thus, greater fatigue-related
      changes in features of the central command (ability to maximally activate a
      muscle and ability to isolate effort to a muscle group) were observed for the
      paretic compared with the non-paretic side. This could be a confounding factor
      when assessing changes in peripheral measures of fatigue following a stroke using
      voluntary contractions.

PMID- 12523951
TI  - The mental health court: an idea whose time has come.

PMID- 12523952
TI  - Psychometric properties of the DSM scale for depression (DSD) with Korean
      American youths.
AB  - As a first step in developing a reliable and culturally sensitive instrument to
      assess depression in Korean-American youths, this community-based methodological
      study was designed to evaluate the characteristics of the DSM Scale for
      Depression (DSD). A total of 104 Korean Americans, 11 to 13 years, participated
      in this study, and the response patterns of this group were compared with Korean-
      (n = 20) and Anglo- (n = 557) American youths assessed by the Teen Life Changes
      Survey (TLCS). Overall, Korean-American youths showed significantly higher mental
      distress scores than Anglos. The DSD was found to be a culturally appropriate
      instrument for Korean Americans with good reliability (alpha =.92) and validity
      demonstrated by correlating with related constructs (loneliness, self-esteem,
      coping, social support, mastery, and somatic symptoms). The highest correlation
      coefficient was observed between depression and somatic symptoms (r =.61). These
      findings are informative for the design of further studies of mental health of
      Korean-American youths.

PMID- 12523953
TI  - An examination of telephone triage in a mental health context.
AB  - Mental health triage is performed via the telephone in some institutions. The
      process by which an accurate mental health assessment can be made over the phone
      has not been documented in the literature. Telephone triage has only been
      comprehensively investigated within the context of Accident and Emergency
      departments. This paper provides a summary of the main issues that arise from
      this literature and then provides a number of research questions that can be
      directed toward telephone triage in a mental health context.

PMID- 12523954
TI  - Terrorism, posttraumatic stress, and religious coping.
AB  - The events of September 11, 2001 triggered a widespread national response that
      was two-fold: a posttraumatic stress reaction and an increase in attendance in
      religious services and practices immediately following the tragic events. The
      following discussion traces the existing research to distinguish this
      posttraumatic stress reaction from posttraumatic stress disorder as a recognized
      psychiatric diagnosis. This disaster reaction is then examined in light of the
      research on religious coping, delineating both its positive and negative aspects
      and the respective outcomes. A conceptual model illustrates the benefits in
      seeking religious comfort for managing a postdisaster stress response. Nursing
      implications for practice are discussed.

PMID- 12523955
TI  - Threshold levels of urinary cadmium in relation to increases in urinary beta2
      microglobulin among general Japanese populations.
AB  - Through literature survey, paired data on cadmium (Cd) and beta(2)-microglobulin
      (beta(2)-MG) levels (as corrected for creatinine concentration) in urine (i.e.,
      Cd-Ucr and beta(2)-MG-Ucr) among Japanese populations were available for 32
      groups of men and 58 groups of women in 12 publications. Plotting of the Cd-Ucr
      and beta(2)-MG-Ucr data for the groups of women showed that beta(2)-MG-Ucr stayed
      unchanged when Cd-Ucr was at lower levels, whereas beta(2)-MG-Ucr increased
      sharply when Cd-Ucr was in excess of 10-20 microg/g cr. Regression analysis was
      made for groups of women with no elevation in beta(2)-MG-Ucr, and those with >400
      or >1000 microg beta(2)-MG-U/g cr. A threshold Cd-Ucr level in relation to an
      increase in beta(2)-MG-Ucr was estimated as Cd-Ucr at the point of intercept of
      the two regression lines, one with no beta(2)-MG-Ucr elevation, and the other
      with >400 or >1000 microg beta(2)-MG-U/g cr. Cd-Ucr at the point of flexion thus
      calculated was 11-12 microg/g cr. Such observation was quantitatively reproduced
      by the analysis of data for men, giving 10-11 microg Cd-U/g cr at the point of
      flexion. This study suggests that the relationship of beta(2)-MG-Ucr with Cd-Ucr
      is not linear but in the shape of letter 'J', i.e., beta(2)-MG-Ucr increases
      sharply when Cd-Ucr is in excess of 10-12 microg/g cr.

PMID- 12523956
TI  - Roles of human liver cytochrome P450 3A4 and 1A2 enzymes in the oxidation of
      myristicin.
AB  - The aim of this work was to identify the form(s) of human liver cytochrome P450
      (CYP) involved in the hepatic transformation of myristicin to its major
      metabolite, 5-allyl-1-methoxy-2,3-dihydroxybenzene. When microsomes prepared from
      different human liver samples were compared, the activity of 5-allyl-1-methoxy
      2,3-dihydroxybenzene formation was well correlated (r(2)=0.87) with nifedipine
      oxidation (a marker of CYP3A4). With a microsomal sample having high CYP3A4
      activity, microsomal oxidation of myristicin to the major metabolite (5-allyl-1
      methoxy-2,3-dihydroxybenzene) was markedly inhibited by gestodene and
      ketoconazole, selective inhibitors of CYP3A enzymes, but not by any of several
      other P450 inhibitors. Antibodies raised against CYPs 3A4 and 1A2 could also
      inhibit the oxidation of myristicin, but antibodies recognizing other CYPs had no
      effect. The oxidation of myristicin to 5-allyl-1-methoxy-2,3-dihydroxybenzene was
      catalyzed by purified bacterial recombinant CYPs 3A4 and 1A2. These results
      provide evidence that CYP3A4 (and possibly other CYP3A enzymes) and CYP1A2 play
      roles in the formation of the major metabolite, 5-allyl-1-methoxy-2,3
      dihydroxybenzene.

PMID- 12523957
TI  - Ambient fine and coarse particle suppression of alveolar macrophage functions.
AB  - Alveolar macrophages (AM) are part of the innate immunological defense system and
      are among the first cells to respond to the effects of inhaled particles. Study
      of macrophage responses to particles is, therefore, relevant to understanding the
      mechanisms by which inhaled particles can adversely affect health. Size
      fractionated ambient particles were collected at traffic-dominated sites in The
      Netherlands using a mobile high volume slit impactor system. AM were obtained by
      bronchoalveolar lavage from adult as well as aged rats and were incubated with
      for 4 h with collected particles at concentrations of 25-1000 pg per cell. Free
      radical generation by AM was measured with and without stimulation of AM with
      phorbol myristate acetate (PMA). There were dose-dependent decreases in
      macrophage production of superoxide radicals as measured by the chemiluminescent
      method. Coarse particles were more toxic than were fine particles. Suppression of
      free radical production did not seem to be related to the presence of
      bioavailable iron or to endotoxin associated with the particles. There were no
      statistically significant differences related to age or strain of the rats
      tested. We conclude that in vitro tests using AM is a useful and rapid method for
      delineating differences in toxicity between environmental samples of size
      fractionated ambient particles.

PMID- 12523958
TI  - Serum albumin binding at cytotoxic concentrations of chemicals as determined with
      a cell proliferation assay.
AB  - The aim of the present study was to measure the influence of albumin binding on
      cytotoxic concentrations of chemicals and to determine binding parameters which
      can be used for quantitative in vitro-in vivo extrapolations. Protein binding
      parameters were determined from cytotoxic potencies measured with Balb/c 3T3
      cells cultured in the presence of 18 and 600 microM bovine serum albumin (BSA). A
      subset of 27 chemicals from the Multicenter Evaluation of In Vitro Cytotoxicity
      (MEIC) project was investigated. At 18 microM BSA the EC(50)-values ranged from
      2.54 microM (As(III)) to 527 mM (ethylene glycol). Increasing the BSA
      concentration either decreased the cytotoxic potency (12 compounds) by factors up
      to 34 (pentachlorophenol), had no effect (14 compounds), or increased the
      cytotoxicity (paraquat). Calculated molar ratios of binding ranged from 0.05
      (Hg(2+)) to 4.8 moles per mole albumin (acetylic salicylic acid). At 18 microM
      BSA fractional binding of most of these compounds was low (<25%) but increased up
      to > or =90% (hexachlorophene, mercuric chloride, thioridazine,
      pentachlorophenol) at 600 microM BSA. The results obtained in general were
      compatible with available protein binding data and can be used to calculate
      equipotent concentrations of chemicals in biological systems containing different
      albumin concentrations.

PMID- 12523959
TI  - Melatonin protects the central nervous system of rats against toluene-containing
      thinner intoxication by reducing reactive gliosis.
AB  - Neuroprotective effects of melatonin against free radical damage have been
      studied extensively. Thinner containing 60-70% toluene is a neurotoxic mixture
      which is widely used as an aromatic industrial solvent. This product has been
      shown to cause functional and structural changes in the central nervous system.
      Toluene generates reactive oxygen species (ROS) and the toxic effects relating to
      these reactants. In the present study we investigated glial reactivity in
      hippocampus, cortex and cerebellum and the expression of glial fibrillary acidic
      protein (GFAP) after exposure of rats to toluene vapor (3000 ppm) for 45 days. We
      also examined the protective effects of melatonin against gliosis. Western blots
      demonstrated a marked elevation in total GFAP, a specific marker for astrocytes,
      by thinner fume inhalation in the hippocampus (P<0.001), cortex (P<0.01) and
      cerebellum (P<0.05) of rats. Melatonin administration prevented the increase of
      total GFAP induced by thinner fume inhalation. Thinner exposure caused a
      significant increase of lipid peroxidation products (malondialdehyde and 4
      hydroxyalkenals) in all brain regions (P<0.01 for each region), and this
      elevation was also was inhibited by melatonin. Furthermore, melatonin augmented
      glutathione levels in all brain regions (P<0.05 for each region) investigated. In
      conclusion, melatonin treatment may provide neuroprotection against toluene
      neurotoxicity by increasing the survival of glial cells possibly by directly
      scavenging ROS and by indirectly augmenting their antioxidant capacity.

PMID- 12523960
TI  - Dichlorodiphenyltrichloroethane suppresses neurite outgrowth and induces
      apoptosis in PC12 pheochromocytoma cells.
AB  - It is well known that dichlorodiphenyltrichloroethane (DDT) is used as an
      insecticide and prevents many people in the tropical zone from devastating
      malaria. On the other hand, a number of reports have indicated that it may act as
      an endocrine disruptor and also has possible carcinogenic effects. However, the
      effects of DDT on the neural cells remain to be investigated. In this study,
      therefore, we observed the effects of p,p'-DDT, o,p'-DDT and its major metabolite
      p,p'-DDE on the differentiation and survival of PC12 pheochromocytoma cells.
      After stimulation with nerve growth factor, PC12 cells exhibited remarkable
      neurite outgrowth, suggesting that neuronal differentiation was induced by this
      growth factor. p,p'-DDT and o,p'-DDT suppressed this neurite outgrowth dose
      dependently, and p,p'-DDE also revealed a similar effect but to a lesser extent.
      Apoptotic cell death was induced within 3-6 h after treatment with p,p'-DDT and
      o,p'-DDT. Again p,p'-DDE showed a weaker apoptosis-inducing effect. In the
      organochlorine-treated PC12 cells phosphorylation of p44/42 mitogen-activated
      protein kinase (MAPK) was upregulated, whereas phosphorylation bands were not
      detected in any kinases of other MAPK groups such as p38 MAPK and SAPK/JNK. A
      kinase assay on p44/42 MAPK revealed that the extent of phosphorylation of Elk-1
      substrates well correlated with the suppressive effect on neuronal
      differentiation and apoptosis-inducing activity. These results suggest that p,p'
      DDT and o,p'-DDT exerted their effects on neuronal cells by the stimulation of
      p44/42 MAPK, and p,p'-DDE had less effects than the other two organochlorines.

PMID- 12523961
TI  - Involvement of calcium channels in the sexual dimorphism of cadmium-induced
      hepatotoxicity.
AB  - Cadmium toxicity has been evaluated in a number of in vivo and in vitro
      toxicological studies. In vivo Cd toxicity exhibits sexual dimorphism with
      females being more susceptible to Cd uptake, accumulation, and toxicity in the
      liver. Research to date does not explain why females are more sensitive to Cd
      induced hepatotoxicity. Recent studies demonstrate that progesterone sensitizes
      female F(344) rats and TRL-1215 cells to Cd toxicity, however the mode of action
      is still unclear. Approximately one half of the Cd entering the cytoplasm does so
      through receptor operated Ca(2+) channels. Progesterone treatment of human
      spermatozoa and Xenopus laevis oocytes causes a rapid influx of Ca(2+) suggesting
      a possible mechanism. Since hepatocytes have progesterone receptors on their
      cellular membrane and Ca(2+) influx into the cytoplasm occurs following
      progesterone treatment we evaluated the hypothesis that progesterone facilitates
      the uptake and accumulation of Cd via Ca(2+) channels, leading to enhanced
      toxicity. Primary isolated rat hepatocytes were treated with Cd, progesterone,
      and/or verapamil for 4 h and cytolethality was measured. Pretreatment with the
      Ca(2+) channel blocker verapamil increased the Cd concentration producing 50%
      lethality (LC(50)) by 2-fold, thus decreasing Cd cytolethality. In contrast,
      pretreatment with progesterone decreased the Cd LC(50) by 2-fold resulting in
      enhanced Cd cytolethality. Verapamil treatment reversed the progesterone enhanced
      Cd cytolethality. Verapamil and/or progesterone in the absence of Cd did not
      affect hepatocyte viability. Overall, the results of this study demonstrate that
      inhibition of progesterone-induced Ca(2+) influx with the Ca(2+) channel blocker
      verapamil, decreases Cd cytolethality in primary isolated rat hepatocytes. These
      findings indicate that progesterone activation of receptor-mediated Ca(2+)
      channels is involved in the sexually dimorphic hepatotoxicity seen following
      acute Cd exposure.

PMID- 12523962
TI  - Effects of low doses of dietary lead on red blood cell production in male and
      female mice.
AB  - The effect of lead (Pb) ingestion on hematological parameters in male and female
      Swiss mice was assessed. Eight different doses of Pb were administered through
      preparation of different feeds. The levels of Pb in the diet were designed to
      provide exposure below (0.6 to <2.0 microg/dl) and above (>2.0-13 microg/dl)
      normal background. One litter of mice was exposed to each Pb dose, with the
      mother given the feed 1 day after mating, and the mother and offspring continuing
      to receive the feed until the litter was 90 days old. Male and female mice
      receiving below normal background levels of dietary Pb displayed enhanced red
      blood cell (RBC) production as measured by increased numbers of RBC and increased
      hemoglobin and hematocrit values. However, as the blood Pb levels approached 10
      microg/dl there was a marked decrease in RBC production. These findings are
      significant since Pb was biologically active in a stimulating manner below
      typical background levels (2.0 microg/dl) while adversely effecting red cell
      synthesis at above background levels (7.0-13 microg/dl) encountered in the
      environment by humans.

PMID- 12523963
TI  - Primary cultures of human hepatocytes as a tool in cytotoxicity studies: cell
      protection against model toxins by flavonolignans obtained from Silybum marianum.
AB  - The aim of this study was to evaluate the cytoprotective effects upon primary
      human hepatocytes of silymarin extract and its main flavonolignans following
      exposure to the cytotoxic actions of model toxins. The conditions for the
      hepatocyte intoxication were optimised for allyl alcohol, carbon tetrachloride, D
      galactosamine and paracetamol. Silymarin extract, silychristin and silydianin did
      not exert cytotoxicity (10-100 microM), whereas silybin and isosilybin at higher
      concentrations and after longer incubation periods were cytotoxic. All main
      flavonolignans of silymarin tested displayed concentration-dependent
      cytoprotection against the toxic effects of both allyl alcohol and carbon
      tetrachloride but neither paracetamol nor galactosamine. The best protection was
      achieved by silydianin and silychristin and to a lesser degree by silymarin,
      while silybin and isosilybin were less effective. It is concluded that these
      differing outcomes result from the varying abilities of the Silybum marianum
      substances tested to stabilize the cell membrane, exert antioxidant properties
      and exhibit intrinsic toxicity.

PMID- 12523964
TI  - Insertion of common mutations into the human beta-globin locus using GET
      Recombination and an EcoRI endonuclease counterselection cassette.
AB  - A large number of mutations have been described in the human beta-globin locus
      causing thalassemia or various hemoglobinopathies. However, only a very limited
      number of these mutations have been studied in animal model systems in the
      context of the human beta-globin locus. We report here the use of the GET
      Recombination system with an EcoRI/Kan(R) counterselection cassette to facilitate
      the introduction of the HbE (codon 26, GAG-->AAG mutation and the codon 41-42 (
      TTCT) deletion, two mutations found in high frequency in South-East Asia, into
      the human beta-globin locus. The counterselection cassette was first inserted
      into the target sequence in the beta-globin gene, and then a PCR fragment
      carrying the required modification was used to replace it. Efficient
      counterselection depends upon the tight regulation of the highly toxic EcoRI
      endonuclease gene by expression of lacI(q). Induction by IPTG during
      counterselection efficiently eliminates non-recombinant bacterial clones. The
      technique can be performed on any known gene sequence using current BAC
      technology, allowing identification and comparative functional analysis of key
      regulatory elements, and the development of accurate animal models for human
      genetic disorders.

PMID- 12523965
TI  - Evaluation of bacterial aerotaxis for its potential use in detecting the toxicity
      of chemicals to microorganisms.
AB  - Bacterial aerotaxis (the movement of a cell toward oxygen) was evaluated for its
      potential use in detecting the toxicity of chemicals to microorganisms. The level
      of toxicity was determined by the concentration of test chemicals resulting in a
      50% inhibition of aerotaxis of Pseudomonas aeruginosa PAO1 after 40 min of
      exposure. The aerotactic responses of P. aeruginosa were measured by using
      chemotaxis well chambers. Each clear acrylic chamber had a lower and upper well
      separated by a polycarbonate filter with a uniform pore size of 8.0 microm. To
      automatically detect bacterial cells that crossed the filter in response to a
      gradient of oxygen, P. aeruginosa PAO1 was marked with green fluorescent protein
      (GFP), and the GFP fluorescence intensity in the upper well was continuously
      monitored by using a fluorescence spectrometer. By using this technique, volatile
      chlorinated aliphatic compounds, including trichloroethylene (TCE),
      trichloroethane, and tetrachloroethylene, were found to be inhibitory to
      bacterial aerotaxis, suggesting their possible toxicity to microorganisms. We
      also examined more than 20 potential toxicants for their ability to inhibit the
      aerotaxis of P. aeruginosa. Based on these experimental results, we concluded
      that bacterial aerotaxis has potential for use as a fast and reliable indicator
      in assessing the toxicity of chemicals to microorganisms.

PMID- 12523966
TI  - Binding of phage displayed Bacillus subtilis lipase A to a phosphonate suicide
      inhibitor.
AB  - Phage display can be used as a protein engineering tool to select proteins with
      desirable binding properties from a library of randomly constructed mutants.
      Here, we describe the development of this method for the directed evolution of
      Bacillus subtilis lipase A, an enzyme that has marked properties for the
      preparation of pharmaceutically relevant chiral compounds. The lipase gene was
      cloned upstream of the phage g3p encoding sequence and downstream of a modified
      g3p signal sequence. Consequently, the enzyme was displayed at the surface of
      bacteriophage fd as a fusion to its minor coat protein g3p. The phage-bound
      lipase was correctly folded and fully enzymatically active as determined from the
      hydrolysis of p-nitrophenylcaprylate with K(m)-values of 0.38 and 0.33 mM for the
      phage displayed and soluble lipase, respectively. Both soluble lipase and lipase
      expressed on bacteriophages reacted covalently with a phosphonate suicide
      inhibitor. The phage does not hamper lipase binding, since both soluble and phage
      bound lipase have a similar half-life of inactivation of approximately 5 min.
      Therefore, we conclude that the Bacillus lipase can be functionally expressed on
      bacteriophages as a fusion to the phage coat protein g3p. The specific
      interaction with the suicide inhibitor offers a fast and reproducible method for
      the future selection of mutant enzymes with an enantioselectivity towards new
      substrates.

PMID- 12523967
TI  - Modification of flavonoid using lipase in non-conventional media: effect of the
      water content.
AB  - The enzymatic acylation of a flavonoid (naringin) was investigated in this work.
      This atypic substrate for a lipase was esterified very selectively by the
      immobilized Candida antarctica lipase: a single product was synthesized and was
      assumed to be the 6-O-palmitate naringin ester acylated on the glucose moiety. As
      lipase-catalyzed esterification reactions in organic media are greatly influenced
      by the water content, the effect of the initial hydration level of the reaction
      medium components was pointed out for naringin palmitate synthesis. 2-Methyl 2
      butanol (solvent) and naringin (acyl acceptor) provided high amounts of water and
      when dried increased the conversion yield by 63% and the specific activity by
      60%. On the contrary, the enzyme must not be dried because water is essential for
      the three-dimensional structure of the protein and, if absent, results in a 67%
      loss of activity. As water was produced in parallel to ester synthesis, the
      equilibrium of the reaction might be shifted by its removal. When the reaction
      was carried out with 100 g l(-1) molecular sieves 4A added after 24 h of
      reaction, a conversion yield of 43% was reached after 55 h reaction.

PMID- 12523968
TI  - A cellulose-binding module of the Trichoderma reesei beta-mannanase Man5A
      increases the mannan-hydrolysis of complex substrates.
AB  - Endo-beta-1,4-D-mannanases (beta-mannanase; EC 3.2.1.78) are endohydrolases that
      participate in the degradation of hemicellulose, which is closely associated with
      cellulose in plant cell walls. The beta-mannanase from Trichoderma reesei (Man5A)
      is composed of an N-terminal catalytic module and a C-terminal carbohydrate
      binding module (CBM). In order to study the properties of the CBM, a construct
      encoding a mutant of Man5A lacking the part encoding the CBM (Man5ADeltaCBM), was
      expressed in T. reesei under the regulation of the Aspergillus nidulans gpdA
      promoter. The wild-type enzyme was expressed in the same way and both proteins
      were purified to electrophoretic homogeneity using ion-exchange chromatography.
      Both enzymes hydrolysed mannopentaose, soluble locust bean gum galactomannan and
      insoluble ivory nut mannan with similar rates. With a mannan/cellulose complex,
      however, the deletion mutant lacking the CBM showed a significant decrease in
      hydrolysis. Binding experiments using activity detection of Man5A and
      Man5ADeltaCBM suggests that the CBM binds to cellulose but not to mannan.
      Moreover, the binding of Man5A to cellulose was compared with that of an
      endoglucanase (Cel7B) from T. reesei.

PMID- 12523969
TI  - The toxicity of textile reactive azo dyes after hydrolysis and decolourisation.
AB  - The toxicity of C.I. Reactive Black 5 and three Procion dyes, as found in textile
      effluents, was determined using the bioluminescent bacterium Vibrio fischeri.
      Hydrolysed Reactive Black had a slightly greater toxicity than the parent form
      (EC(50) 11.4+/-3.68 and 27.5+/-4.01 mg l(-1), respectively). A baffled bioreactor
      with anaerobic and aerobic compartments was used to decolourise hydrolysed
      Reactive Black 5 in a synthetic effluent. Decolourisation of hydrolysed Reactive
      Black resulted in an increased toxicity (EC(50) 0.2+/-0.03 mg l(-1)). Toxicity
      was not detectable when decolourised Reactive Black 5 was metabolised under
      aerobic conditions. No genotoxicity was detected after the decolourisation of
      either the parent or the hydrolysed reactive dyes, either in vitro or in the
      bioreactor. The toxicity and genotoxicity of decolourised C.I. Acid Orange 7 was
      due to the production of 1-amino-2-naphthol (EC(50) 0.1+/-0.03 mg l(-1)).

PMID- 12523970
TI  - Decolorization of the textile dyes by newly isolated bacterial strains.
AB  - Six bacterial strains with the capability of degrading textile dyes were isolated
      from sludge samples and mud lakes. Aeromonas hydrophila was selected and
      identified because it exhibited the greatest color removal from various dyes.
      Although A. hydrophila displayed good growth in aerobic or agitation culture (AGI
      culture), color removal was the best in anoxic or anaerobic culture (ANA
      culture). For color removal, the most suitable pH and temperature were pH 5.5
      10.0 and 20-35 degrees C under anoxic culture (ANO culture). More than 90% of RED
      RBN was reduced in color within 8 days at a dye concentration of 3,000 mg l(-1).
      This strain could also decolorize the media containing a mixture of dyes within 2
      days of incubation. Nitrogen sources such as yeast extract or peptone could
      enhance strongly the decolorization efficiency. In contrast to a nitrogen source,
      glucose inhibited decolorization activity because the consumed glucose was
      converted to organic acids that might decrease the pH of the culture medium, thus
      inhibiting the cell growth and decolorization activity. Decolorization appeared
      to proceed primarily by biological degradation.

PMID- 12523971
TI  - A thermostable alpha-arabinofuranosidase from xylanolytic Bacillus pumilus:
      purification and characterisation.
AB  - Bacillus pumilus PS213 secretes an alpha-L-arabinofuranosidase (AF) when grown in
      the presence of arabinogalactan or oat meal. The enzyme has been purified to
      homogeneity and characterised. Its molecular mass, as determined by gel
      filtration, is 220 kDa, while sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) showed a single band of approximately 60 kDa.
      According to the result of the mass spectrometry analysis showing a molecular
      mass of 56 kDa, the enzyme should be a homotetramer. The isoelectric point was
      found to be 5.2, the enzyme activity was optimal at 55 degrees C and pH 7.0. The
      enzyme retained 80% of its activity after 2 h at 65 degrees C and lost 50% of
      activity at 75 degrees C after 135 min. The Michaelis constant K(m) and V(max)
      for p-nitrophenylarabinofuranoside at 37 degrees C were 1.7 mM and 52.9 U mg(-1),
      respectively. N-terminal sequence analysis and internal peptide fragments showed
      homology with glycosyl hydrolases of family 51.

PMID- 12523973
TI  - Degradation of N-acylhomoserine lactones, the bacterial quorum-sensing molecules,
      by acylase.
AB  - Porcine kidney acylase I was shown to be able to deacylate N-acylhomoserine
      lactones, a family of chemicals employed by Gram-negative bacteria as quorum
      sensing molecules for cell population density-dependent growth (such as biofilm
      formation). The enzyme transformed both N-butyryl-and N-octanoyl-L-homoserine
      lactones into L-homoserine. An optimal pH of 10 at 23 degrees C and an optimal
      temperature of 76 degrees C at pH 9 were found for the enzyme in hydrolyzing N
      butyryl-homoserine lactone. At pH 9 and 23 degrees C, the enzymatic catalysis had
      a K(m) of 81+/-3 mM and a k(cat) of 127+/-2 nmol min(-1) per mg. The enzyme was
      also shown to be able to reduce the biofilm growth in an aquarium water sample.
      Potential physiological significance and medicinal/industrial applications of the
      N-acylhomoserine lactone-degrading activity of acylase are discussed.

PMID- 12523972
TI  - Coexpression of BiP increased antithrombotic hirudin production in recombinant
      Saccharomyces cerevisiae.
AB  - In order to increase a production level of antithrombotic hirudin, BiP was
      simultaneously expressed in recombinant Saccharomyces cerevisiae strains carrying
      ten and 15 copies of the hirudin expression cassette integrated in the
      chromosome. Coexpression of BiP greatly enhanced both cell growth and hirudin
      production in recombinant S. cerevisiae. Maximum hirudin concentration of 36 mg
      l(-1) was obtained from batch culture of the ten copy-number transformant
      concomitantly harboring an episomal copy of the BiP gene under the control of the
      GAL1 promoter, which is corresponding to a 2.5-fold increase compared with the
      control strain carrying the genomic BiP gene only. The mean size of the
      recombinant yeast cells expressing the BiP gene remained at a relatively constant
      level compared with the control strains of which size increased after the onset
      of hirudin expression by the GAL10 promoter.

PMID- 12523974
TI  - Reactivity against Sarcocystis neurona and Neospora by serum antibodies in
      healthy French horses from two farms with previous equine protozoal
      myeloencephalitis-like cases.
AB  - Sarcocystis neurona is considered a leading cause of equine protozoal
      myeloencephalitis (EPM), a common infectious neurological disease in horses in
      the Americas. EPM-like cases associated with S. neurona peptide reactive
      antibodies in Western blots were recently described in Normandy, France. In this
      report, antibodies reacting with S. neurona merozoites were detected using an
      agglutination assay at titers ranging from 50 to 500 in sera from 18/50 healthy
      horses from two farms with a previous EPM-like case. Higher values were found in
      older animals. Four out of six horses which traveled or stayed in the US
      exhibited titers over 50, a higher figure than in the group which did not travel
      out of France or stayed in an other European country. No correlation was found
      between anti-S. neurona and anti-Neospora sp. antibody titers. Data prompt
      further study of significance of anti-S. neurona antibodies in clinically healthy
      or diseased European horses, and identification of putative immunizing
      parasite(s) and their host(s).

PMID- 12523975
TI  - Immunohistochemical distribution of antigens in liver of infected and immunized
      pigs with Ascaris suum.
AB  - In the present work, we carry out an immunopathological study of the swine
      ascariosis, under different conditions (control, infection and immunization).
      Twenty-one Iberian pigs were used and divided in seven groups. Groups 1 and 2
      were the uninfected and challenged controls, respectively. Groups 3 and 4 were
      weakly infected with increasing doses of Ascaris suum eggs and treated with
      pyrantel (Group 4). Groups 5-7 were immunized with 14, 42 and 97 kDa proteins
      from the parasite, respectively. Groups 2-7 were challenged with 10,000 infective
      eggs 7 days before the sacrifice. The focal parasitic granulomata with
      eosinophils and lymphocytes were the main histopathological lesions in the liver
      of reinfected pigs, while more marked cellular infiltrate and abundant connective
      tissue were seen in the livers of immunized animals. There were important
      deposits of antigens in the livers of immunized and infected pigs. Antigens were
      mainly located in the connective tissue, with positive staining detection of the
      somatic larvae antigen, the body wall from the adult worms and the 14-, 42- and
      97-kDa proteins. However, cholangiols, biliary ducts and macrophages presented an
      immunohistochemical positive stain against excretory-secretory and somatic
      antigens from the larvae and the body fluid antigen from the adult parasite. The
      detection of A. suum antigens in the liver of infected pigs improves the
      diagnosis of swine ascariosis. It may be possible to apply these procedures for
      diagnosis of human ascariosis in liver biopsies since A. suum from swine have
      been previously used as a substitute for the study of the human parasite Ascaris
      lumbricoides.

PMID- 12523976
TI  - In vitro growth requirements for the fish pathogen Philasterides dicentrarchi
      (Ciliophora, Scuticociliatida).
AB  - Philasterides dicentrarchi is a scuticociliate causing fatal disease in farmed
      turbot and sea bass. In view of its high virulence and endoparasitic location,
      this parasite cannot be effectively controlled by formalin baths, and no systemic
      chemotherapeutic treatments have yet proved effective; immunoprophylaxis may thus
      be an attractive alternative approach. Since vaccine development is greatly
      facilitated by axenic culture of the pathogen, we have developed a simple axenic
      culture system based on commercially available Leibovitz L-15 medium,
      supplemented with fetal bovine serum, lipids (lecithin and Tween 80), nucleosides
      and glucose. After 1 week's culture under optimal conditions (salinity 10 per
      thousand, pH 7.2, temperature between 18 and 23 degrees C), yields of 1-2 x
      10(5)cells/ml were obtained. Even cultures with seeding densities as low as 20
      cells/ml were found to produce a good yield of ciliates (about 6 x 10(4)cells/ml)
      after 11 days of incubation. The ciliates thus obtained were free of
      contamination by other microorganisms, enabling preparation of pure P.
      dicentrarchi antigens for vaccine development studies.

PMID- 12523977
TI  - Giardia duodenalis trophozoites isolated from a parrot (Cacatua galerita)
      colonize the small intestinal tracts of domestic kittens and lambs.
AB  - This study examines the ability of Giardia duodenalis trophozoites, isolated from
      a wild bird, to colonize the intestinal tracts of companion animals (kittens) and
      domestic ruminants (lambs). Trophozoites colonized the intestinal tracts of
      intraduodenally inoculated animals as demonstrated by increasing parasite burdens
      within the duodenum and jejunum and by fecal passage of cysts within 4 days post
      inoculation. The pathogenesis of the trophozoites was further investigated in
      kittens. In these animals, infection significantly reduced jejunal brush border
      microvillous length and density, which resulted in a loss of overall epithelial
      brush border surface area. This injury was associated with the production of
      diarrhea in four of five infected kittens. These findings indicate that some bird
      species may carry G. duodenalis that represent a possible health threat to
      companion animals and livestock. Our results describe the first successful
      colonization of avian-derived G. duodenalis trophozoites in the small intestines
      of domestic kittens and lambs.

PMID- 12523978
TI  - Comparison of viability assays for Cryptosporidium parvum oocysts after
      disinfection.
AB  - In order to test various viability assays for Cryptosporidium parvum oocysts were
      used to infect HCT-8 cells in vitro or baby mice. Infected cells were either
      stained with fluorescent anti-Cryptosporidium-antibody or lysed and subjected to
      C. parvum-specific PCR after 48 h. Titrations with infective oocysts were
      performed and compared to oocysts disinfected with Neopredisan for 2 h at varying
      concentrations. Caecal smears and histological sections from infected animals
      were examined in parallel. The number of foci of parasite development in vitro
      after immunofluorescent staining correlated well with the infection dose. PCR was
      less quantifiable and the results were not always reproducible, especially when
      low infection doses were used. Disinfection resulted in a dose-dependent
      reduction of oocyst infectivity when compared to the controls in all three
      assays. The infection of cells cultured in vitro with oocysts of C. parvum
      provides a suitable tool for the estimation of viability after treatment with
      chemical disinfectants. Immunofluorescence is easy to perform and gives
      quantitative results, while PCR-based detection of parasite DNA, although
      possible, requires the use of more sophisticated tools for quantification.

PMID- 12523979
TI  - Antibody levels by indirect ELISA test in Trypanosoma evansi infected horses
      following treatment with quinapyramine sulphate.
AB  - An ELISA test was used to determine the persistence of antibody levels in horses
      following treatment for Trypanosoma evansi. In 17 horses with T. evansi from two
      farms treated and cured with quinapyramine sulphate, ELISA antibody levels fell
      progressively post-treatment, but remained with positive results for 22.6 months
      in one horse, 12.8 months in a second, 4.1 months in another four and 2.3 months
      in three, whilst the rest became negative at 2.3 months. In two horses that
      suffered a post-treatment infection relapse the decrease in ELISA levels was only
      temporary, and a new increase in antibody levels was proven. The follow-up of
      these antibody levels could prove useful in clinical cases and in epidemiological
      studies, as well as for assessing the efficacy of drug treatment.

PMID- 12523980
TI  - Pre-exposure of cattle to drug-abbreviated Fasciola hepatica infections: the
      effect upon subsequent challenge infection and the early immune response.
AB  - In this study we examined whether juvenile liver flukes are capable of
      stimulating protective immune responses in cattle. Four experimental groups of
      cattle were studied as follows: group A, a positive control, received a primary
      infection on day 0 and a secondary infection 28 days later; group B also received
      two infections but the primary infection was terminated by drug treatment on day
      5; group C, received infections on days 0, 5 and 10 which were terminated by drug
      treatments on days 1, 6 and 11 and then a secondary infection on day 28; group D
      received an infection only on day 28. Juvenile flukes appear to induce protective
      responses because: (a) group B animals had significantly lower levels of gamma-GT
      (P<0.05) than group D; (b) both groups B and C exhibited lower parenchymal phase
      GLDH levels (P=0.006 and 0.041, respectively); and (c) both groups B and C had
      lower secondary phase eosinophilia (P=0.002 and 0.02, respectively) than those in
      group D. Sera taken from groups A-C contained antibodies reacting to a variety of
      proteins in adult fluke somatic antigen and excretory-secretory preparations,
      particularly to proteins of 52-60, 68-72 and 82-96 kDa. After secondary challenge
      the antibody responses of group A to these proteins declined while reactivity to
      proteins of 28-30 kDa increased. Antibody responses to the 28-30 kDa proteins
      were not detected in groups B-D until 3 weeks later than those observed in group
      A. Antibody responses to Fasciola hepatica cathepsin L proteases, which are known
      to induce protection, were monophasic, of the IgG1 isotype only and were not
      observed prior to secondary challenge in any of the four groups. In contrast, the
      response to another protective antigen fraction, a high molecular sized haem
      protein, was of a mixed IgG1/IgG2 nature and was detected within 14 days of
      primary infection. However, no significant difference in antibody titres to
      either protein preparation was observed after the secondary infection when groups
      B and C were compared to group D.

PMID- 12523981
TI  - Taenia saginata derived synthetic peptides with potential for the diagnosis of
      bovine cysticercosis.
AB  - Immunity in Taeniids is predominantly antibody mediated and thus many serological
      immuno-determinants will have potential in both protection and diagnosis. The
      antigenicity of six peptides derived from four potentially protective molecules
      cloned from a Taenia saginata oncospheres cDNA library have been evaluated as
      targets for the specific diagnosis of bovine cysticercosis. The six peptides
      consist of: two peptides (HP6-2 and HP6-3) derived from the sequence of the 18
      kDa surface/secreted oncospheral adhesion antigen identified by McAb-HP6, two
      peptides (Ts45W-1 and Ts45W-5) derived from the sequence of the T. saginata
      homologue of the T. ovis 45W protective gene family, one peptide (TS45S-10)
      derived from a T. saginata sequence with significant similarity to the T. ovis
      45S protective antigen, and one peptide (TEG-1) derived from the sequence of the
      T. saginata homologue of Echinococcus spp. main surface protein. Longitudinal
      studies indicate that T. saginata infected cattle respond to all six peptides by
      3-4 weeks post-infection and that the antibody levels remain high for at least 12
      weeks post-infection. As protection against Taeniid parasites is predominantly
      antibody mediated, some of these six peptides may be of value as immuno
      prophylactic tools and hence also in assays to determine resistance to infection
      with the parasite. For diagnosis, on the other hand, only three peptides (HP6-2,
      TEG-1 and Ts45S-10) performed with the necessary sensitivity and specificity to
      determine exposure to infection with T. saginata, and now merit an exhaustive
      evaluation prior to employment as routine diagnostic tools.

PMID- 12523982
TI  - Experimental infection with the Paderborn isolate of classical swine fever virus
      in 10-week-old pigs: determination of viral replication kinetics by quantitative
      RT-PCR, virus isolation and antigen ELISA.
AB  - We performed experimental infection in 10-week-old pigs with the Paderborn
      isolate of classical swine fever virus (CSFV). Despite being epidemiologically
      linked to the major CSFV outbreak in The Netherlands in 1997, the in vivo
      replication kinetics of this isolate have to our knowledge not been described in
      detail previously. We found that oronasal infection with 10(4.7) TCID(50)
      produced mortality in three out of five pigs after 29-31 days, and severe
      clinical symptoms in one out of five pigs, while one out of five pigs exhibited
      no clinical symptoms. At this infection dose, pigs had viral RNA (monitored by
      quantitative reverse transcription (RT)-PCR) in serum as soon as 2 days post
      infection, and excretion of infectious virus (monitored by sentinel pigs)
      appeared to be virtually concomitant with viremia onset. While virus RNA was
      cleared from the serum of most pigs after 1-2 weeks, some pigs had viral RNA in
      serum for more than 30 days, and exhibited only mild clinical symptoms. We
      observed an excellent correlation between clinical symptoms and viral RNA loads
      in serum, while serum antibody levels were low. Clinically affected pigs had up
      to 1000-fold higher serum viral RNA loads than did pigs without clinical
      symptoms. At this level of infection, and this age group, the Paderborn isolate
      exhibited a strikingly wide range of replication patterns, which might be
      relevant to the spread of the virus through susceptible pig populations, and the
      severity of the 1997-1998 outbreak.

PMID- 12523983
TI  - Intracellular survival of Brucella: defining the link with persistence.
AB  - Brucellosis is caused by a facultative intracellular pathogen that invades both
      professional and non-professional phagocytic cells. Resistance to killing in
      professional phagocytic cells controls survival and chronic infection. Resistance
      of the organism to killing appears to derive from altered intracellular
      trafficking of Brucella containing vacuoles to the endoplasmic reticulum via the
      autophagic pathway. Acute infection is observed in pregnant ruminants in which
      invasion of the chorionic trophoblasts results in abortion. Following abortion
      persistence of the organism is observed in the mammary gland and lymph nodes of
      ruminants. The risk of multiple abortions and subsequent shedding of the organism
      in the milk has resulted in the culling of infected animals. Persistence of the
      organism in the reticuloendothelial system is a primary symptom in human
      infection and may persist over several decades. We have employed the mouse model
      of brucellosis to characterize genes responsible for persistent infection in an
      effort to identify potential drug targets for elimination of infection or to
      attenuate potential vaccine candidates. The results suggest that Brucella
      utilizes a battery of metabolic functions to sustain itself in intracellular
      environments in conjunction with altering the intracellular course of infection.

PMID- 12523984
TI  - Colonisation phenotype and colonisation potential differences in Campylobacter
      jejuni strains in chickens before and after passage in vivo.
AB  - Campylobacter jejuni strains isolated from chicken faeces and from humans
      suffering from gastroenteritis were used to determine the colonisation phenotypes
      and colonisation potential of these strains in chickens. Five different
      colonisation types were observed ranging from immediate and sustained
      colonisation to completely non-colonising. Phenotype one showed immediate
      colonisation with prolonged excretion of viable C. jejuni bacteria. Phenotype two
      showed delayed colonisation with prolonged excretion of viable C. jejuni
      bacteria. Phenotype three showed immediate colonisation and delayed clearing of
      viable C. jejuni bacteria. Phenotype four showed delayed colonisation and delayed
      clearing of viable C. jejuni bacteria. Strains of phenotype five could not
      colonise chickens. Inoculum levels to obtain maximum caecal colonisation for each
      phenotype for strains cultured in vitro and in vivo was also determined.
      Following passage in vivo through a chicken, the minimum inoculum required for
      sustained colonisation dropped approximately 1000-fold, however, the colonisation
      phenotype remained unchanged before and after a passage in vivo.

PMID- 12523985
TI  - Use of cecal microflora cultured under aerobic or anaerobic conditions in the
      control of experimental infection of chicks with Salmonella Enteritidis.
AB  - One-day-old broiler chicks received cecal microflora (CM) cultured under aerobic,
      anaerobic conditions, or both (mixed) and were then infected with Salmonella
      Enteritidis, in order to compare the efficacy of these different types of culture
      in terms of the number of chicks infected, cecal colonization and faecal
      excretion of the challenging bacteria. Regardless of culture type, CM always led
      to a smaller number of S. Enteritidis for any of the parameters studied compared
      to untreated chicks. Aerobic CM demonstrated better efficacy in reducing the
      number of infected chicks and cecal colonization by S. Enteritidis, followed by
      mixed CM. No difference was observed in faecal excretion of S. Enteritidis
      between the chicks that received different types of CM culture.

PMID- 12523986
TI  - Prepartum teat apex colonization with Staphylococcus chromogenes in dairy heifers
      is associated with low somatic cell count in early lactation.
AB  - A high number of dairy heifers freshen with udder health problems. The prevalence
      of teat apex colonization (TAC) with Staphylococcus chromogenes, one of the most
      widespread coagulase-negative staphylococci (CNS) in milk samples from freshly
      calved dairy heifers, was measured cross-sectionally in non-lactating heifers on
      eight commercial dairy farms in Belgium. The influence of age on this prevalence,
      and the association between teat apex colonization with S. chromogenes prepartum
      and quarter milk somatic cell count (SCC) in early lactation were studied. In
      total, 492 teat apices were sampled from 123 heifers. The age of the heifers
      varied from 8 to 34 months. Overall, 20% of the heifers had at least one teat
      apex colonized with S. chromogenes. Of all teats sampled, 10% were colonized with
      S. chromogenes. The chance of having at least one teat apex colonized with S.
      chromogenes increased with age of the heifer. The presence of prepartum teat apex
      colonization with S. chromogenes was not associated with intramammary infection
      (IMI) early postpartum with the same bacterium. On the contrary, teat apex
      colonization with S. chromogenes prepartum appeared to protect quarters in the
      first few days of lactation from having somatic cell count >or=200000cells/ml
      milk, commonly accepted as the threshold for intramammary infection.

PMID- 12523987
TI  - Typing of Haemophilus parasuis strains by PCR-RFLP analysis of the tbpA gene.
AB  - On the basis of a species-specific PCR assay, a RFLP analysis for typing of
      Haemophilus parasuis strains was developed and evaluated. Amplification was based
      on the gene tbpA, encoding a transferrin-binding protein. RFLP analysis of the
      1.9-kb tbpA-amplicon using TaqI, AvaI and RsaI endonucleases produced 12
      different patterns for the reference strains of the 15 known H. parasuis
      serovars, and showed a high heterogeneity (33 RFLP groups) for 101 H. parasuis
      clinical isolates tested. The sensitivity, typeability (100% versus 65% for
      immunodiffusion), high degree of discrimination (0.93 versus 0.84 for
      immunodiffusion), simplicity and low cost per test make this PCR-RFLP assay a
      useful method for typing H. parasuis and, therefore, for studying the
      epidemiology of outbreaks of Glasser's disease.

PMID- 12523988
TI  - Cytotoxic activity of Mannheimia haemolytica strains in relation to diversity of
      the leukotoxin structural gene lktA.
AB  - The leukotoxin of Mannheimia haemolytica has a very high degree of amino acid
      diversity because the lktA gene has a complex mosaic structure that has been
      derived by horizontal DNA transfer and intragenic recombination. The objective of
      the present study was to determine the effect of this amino acid diversity on
      leukotoxin cytotoxicity against bovine and ovine cell types. This was done by
      comparing the luminol-dependent chemiluminescence response of bovine and ovine
      neutrophils after pre-incubation with the various leukotoxin types. The LktA1.1
      type leukotoxin associated with bovine serotype A1 and A6 strains differs from
      the LktA1.2-type leukotoxin produced by ovine serotype A1 and A6 strains at a
      single amino acid position and has enhanced activity against bovine but reduced
      activity against ovine neutrophils. These findings, together with the exclusive
      association of the LktA1.1-type leukotoxin with bovine strains, suggest that this
      leukotoxin type has an adaptive advantage in the bovine host. Leukotoxins LktA6
      LktA10 are associated with ovine strains and have complex mosaic structures and
      diverse amino acid sequences but similar levels of cytotoxic activity against
      bovine and ovine neutrophils, respectively. However, ovine neutrophils were more
      sensitive to the cytotoxic activities of these leukotoxins than were bovine
      neutrophils. LktA8- and LktA10-type leukotoxins are associated with serotype A2
      and A7 strains that are responsible for the majority of ovine disease cases, but
      LktA6-, LktA7- and LktA9-type leukotoxins are associated with less common
      serotypes. These findings contribute to the growing body of evidence suggesting
      that factors other than leukotoxin cytotoxicity are responsible for the full
      expression of virulence in M. haemolytica. Overall, the extensive recombinational
      exchanges within the lktA gene of M. haemolytica have had little effect on
      leukotoxin function which is highly conserved.

PMID- 12523989
TI  - First evidence of bluetongue virus in Kazakhstan.
AB  - We report the results of the first serological survey for bluetongue virus in
      Kazakhstan. We analysed blood samples collected from 958 livestock and 513 wild
      saiga antelopes over a large area of the country, and found 23.2% seroprevalence
      in livestock and 0% in saigas. Seroprevalence in livestock did not vary by
      species, but increased significantly with age. There was no evidence for
      variation in seroprevalence at the regional level, but there was significant
      clustering at the farm level. Bluetongue has never before been reported in
      Kazakhstan, yet our results suggest that it may be endemic. We found seropositive
      animals at the furthest known northern limits of the bluetongue virus in this
      region of the world. Recorded vectors are not known to be present in Kazakhstan,
      so a novel vector is likely to be operating. The lack of evidence for bluetongue
      virus in saigas is unexpected and suggests a need for further investigation.

PMID- 12523990
TI  - Canine distemper of vaccine origin in European mink, Mustela lutreola--a case
      report.
AB  - Cases of canine distemper (CD) related to vaccination of exotic carnivores extend
      over three decades and have been described in at least nine different species.
      Our report describes a case of acute CD in a European mink, Mustela lutreola,
      vaccinated with live attenuated CD vaccine licensed for use in fur-farmed mink.
      The male mink died of an acute grey matter disease with an unusually long
      incubation period. A female vaccinated at the same time showed no obvious signs
      of illness. The diagnosis was confirmed by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and by subsequent sequencing of the PCR products. The sequenced
      products of the virus isolated from the mink and of the vaccine batch showed 100%
      identity. This is the first report in which molecular methods were used to
      confirm that the disease was caused by the vaccine strain. Based on our findings,
      it is clearly evident that current CD vaccines cannot be safely used in exotic
      species.

PMID- 12523992
TI  - Three-dimensional analysis of plant structure using high-resolution X-ray
      computed tomography.
AB  - High-resolution X-ray computed tomography (HRCT) is a non-invasive approach to 3D
      visualization and quantification of biological structure. The data, based on
      differential X-ray attenuation, are analogous to those otherwise obtainable only
      by serial sectioning. Requiring no fixing, sectioning or staining, HRCT produces
      a 3D digital map of the specimen that allows measurements and visualizations,
      including arbitrarily oriented sections. In spite of its application throughout
      the natural sciences, HRCT has yet to be applied in extant plant structural
      research.

PMID- 12523993
TI  - Vitamin E biosynthesis: biochemistry meets cell biology.
AB  - Vitamin E is thought to be involved in many essential processes in plants, but no
      functional proof has been reported. To study vitamin E deficiency in plants, a
      high-throughput biochemical screen for vitamin E quantification in Arabidopsis
      mutants has been developed, which has led to the identification of VTE1-encoding
      tocopherol cyclase. Interestingly, the corresponding maize mutation, sxd1, causes
      plasmodesmata malfunction, suggesting a link between tocopherol cyclase and
      plasmodesmata function.

PMID- 12523994
TI  - Virtual plants: modelling as a tool for the genomics of tolerance to water
      deficit.
AB  - Modelling can simulate the responses of virtual plants carrying diverse
      combinations of alleles under different scenarios of abiotic stress. The main
      difficulty is mathematically expressing the genetic variability of responses to
      environmental conditions. Modelling via gene regulatory networks is not feasible
      for such complex systems, but plants can be modelled using response curves to
      environmental conditions that are 'meta mechanisms' at plant level. Each genotype
      is represented by a set of response parameters that are valid under a wide range
      of conditions. Transgenesis of one function experimentally affected one response
      parameter only. Transgenic plants or plants carrying any combination of
      quantitative trait loci might therefore be simulated and tested under different
      climatic scenarios, before genetic manipulations are performed.

PMID- 12523995
TI  - Cyclic, pseudocyclic and noncyclic photophosphorylation: new links in the chain.
AB  - Photosynthetic electron transport is coupled to ATP synthesis. This process -
      photosynthetic phosphorylation - proceeds by several alternative electron
      transport pathways in isolated chloroplasts. The question: 'Which of these works
      in real life?' has long occupied students of photosynthesis. Recent results from
      structural biology and genomics suggest that the answer is 'All of them'. The
      interplay between the pathways might explain the flexibility of photosynthesis in
      meeting different metabolic demands for ATP.

PMID- 12523996
TI  - Abscisic acid, nitric oxide and stomatal closure - is nitrate reductase one of
      the missing links?
AB  - Once plant endogenous nitric oxide (NO) production had been proved, NO research
      was directed toward both the source and the targets of this extremely bioactive
      molecule. As in mammals, plant NO was first thought to be generated mainly by a
      NO synthase-like enzymatic activity. However, nitrate reductase (NR)-dependent NO
      production is now receiving much of the attention because of the ubiquity of this
      enzyme in higher plant tissues and the precise regulation of its NO-production
      activity. NO has been reported to be a signal in many and diverse physiological
      processes, such as growth and biotic and abiotic stresses. Recently, NO has been
      shown to affect stomatal closure and interact with abscisic acid signaling
      pathways. We propose NR as a putative component in the signaling cascade of ABA
      induced stomatal closure.

PMID- 12523997
TI  - Balancing the central roles of the thylakoid proton gradient.
AB  - The photosynthetic electron transfer chain generates proton motive force (pmf),
      composed of both electric field (Deltapsi) and concentration (DeltapH) gradients.
      Both components can drive ATP synthesis, whereas the DeltapH component alone can
      trigger feedback regulation of the antenna. It has often been suggested that a
      relatively large pmf is needed to sustain the energetic contributions of the ATP
      synthase reaction (DeltaG(ATP)), and that the Deltapsi component is dissipated
      during illumination, leading to an acidic lumen in the light. We suggest that
      this is incompatible with the stabilities of lumenal components and the observed
      activation of downregulation. Recent work on the chloroplast ATP synthase
      suggests that a more moderate pmf can sustain DeltaG(ATP). In addition, in vivo
      probes suggest that a substantial fraction of pmf can be stored as Deltapsi.
      Together, these factors should allow sufficient DeltaG(ATP) to maintain lumen pH
      in a range where lumenal enzyme activities are nearly optimal, and where the
      level of NPQ is regulated.

PMID- 12523998
TI  - Chloroplast redox signals: how photosynthesis controls its own genes.
AB  - The photosynthetic apparatus of higher plants and algae is composed of plastid-
      and nuclear-encoded components, therefore the expression of photosynthesis genes
      needs to be highly coordinated. Expression is regulated by various factors, one
      of the most important of which is light. Photosynthesis functions as a sensor for
      such light signals, and the redox state of photosynthetic electron transport
      components and redox-active soluble molecules act as regulating parameters. This
      provides a feedback response loop in which the expression of photosynthesis genes
      is coupled to the function of the photosynthetic process, and highlights the dual
      role of photosynthesis in energy fixation and the reception of environmental
      information.

PMID- 12524000
TI  - How useful are animal models of human disease?

PMID- 12523999
TI  - Plant snoRNAs: functional evolution and new modes of gene expression.
AB  - Small nucleolar RNAs (snoRNAs) are a well-characterized family of non-coding RNAs
      whose main function is rRNA modification. The diversity and complexity of this
      gene family continues to expand with the discovery of snoRNAs with non-rRNA or
      unknown targets. Plants contain more snoRNAs than other eukaryotes and have
      developed novel expression and processing strategies. The increased number of
      modifications, which will influence ribosome function, and the novel modes of
      expression might reflect the environmental conditions to which plants are
      exposed. Polyploidy and chromosomal rearrangements have generated multiple copies
      of snoRNA genes, allowing the generation of new snoRNAs for selection. The large
      snoRNA family in plants is an ideal model for investigation of mechanisms of
      evolution of gene families in plants.

PMID- 12524001
TI  - Modelling human diseases in Drosophila and Caenorhabditis.
AB  - Drosophila (fruitfly) and Caenorhabditis (nematode worm) are useful model
      organisms for understanding many molecular and cellular mechanisms of human
      disease. Work on them is powered by versatile gene discovery methods, output of
      their genome projects, and a biology that has much in common with that of humans.
      They contain homologues of most human disease genes. Many aspects of human
      disease, and of defences against disease, are also found in flies and worms.
      These include cancer, ageing, neurodegeneration, infectious disease, innate
      immunity, and dysfunction of neurotransmitter and endocrine systems.

PMID- 12524002
TI  - The zebrafish as a tool for understanding the biology of visual disorders.
AB  - Retinal degenerations are the commonest cause of blindness in the Western world,
      affecting 5% of the population, yet remain largely untreatable. A better
      understanding of the mechanisms of disease is needed. Zebrafish fill a gap in the
      current repertoire of models, offering genetic tractability in a vertebrate.
      Their retina has many similarities with a human retina. Importantly, unlike
      rodents, they have rich colour vision, offering the potential to model the
      macular degenerations. A variety of physiological assays, genetic manipulations
      and histological tools have been developed and useful models of human disease
      created.

PMID- 12524003
TI  - Mutagenesis strategies for identifying novel loci associated with disease
      phenotypes.
AB  - The systematic identification of the function of all the genes in the mammalian
      genome is one of the major scientific challenges for the 21st century. A
      comprehensive insight into mammalian gene function will illuminate our
      understanding of the genetic bases of disease. Mouse mutagenesis is a powerful
      tool for the study of mammalian gene function. Most recently, a number of
      approaches employing the chemical mutagen ethylnitrosourea (ENU) have been
      utilised by mouse geneticists to deliver a substantial new collection of mouse
      disease models. The growing mouse mutant archive provides a powerful resource for
      the identification of novel genes involved with human genetic disease.

PMID- 12524004
TI  - Mouse models as tools for dissecting disorders of lipoprotein metabolism.
AB  - The overexpression of proteins as transgenes or by adenovirus-mediated gene
      transfer as well as the disruption of genes by homologous DNA recombination in
      the mouse provide powerful tools to dissect the role of individual proteins in
      complex biological pathways. These and similar techniques have been widely used
      to characterize the function of most of the players involved in lipoprotein
      metabolism. These models are expected to greatly advance the finding of new
      therapeutic strategies for the treatment of disorders of lipoprotein metabolism.

PMID- 12524005
TI  - Animal models of anxiety and their molecular dissection.
AB  - Genetic approaches to psychiatric illness need appropriate animal models both for
      investigating how genetic variants give rise to behavioural disorder and for
      identifying genes that may be important in human conditions. Yet the relevance of
      many animal models to psychiatric illness is often not clear. Here I discuss how
      genetic approaches can be used to validate animal models of anxiety, an approach
      which is applicable to other animal models. One drawback of genetic validation is
      the difficulty inherent in identifying the molecular variants that influence the
      phenotype. I review genetic approaches that have the potential to overcome this
      problem.

PMID- 12524006
TI  - Genomic imprinting--insights from studies in mice.
AB  - A subset of mammalian genes is controlled by genomic imprinting. This process
      causes a gene to be expressed from only one chromosome homologue depending on
      whether it originally came from the egg or the sperm. Parental origin-specific
      gene regulation is controlled by epigenetic modifications to DNA and chromatin.
      Genomic imprinting is therefore a useful model system to study the epigenetic
      control of genome function. Here we consider the value of the mouse as an
      experimental organism to address questions about the role of imprinted genes,
      about the regulation of mono-allelic gene expression and about the evolution of
      the imprinting function and mechanism.

PMID- 12524007
TI  - Introduction: epigenetic strategies in animals and plants.

PMID- 12524008
TI  - DNA methylation in animal development.
AB  - Nuclear transfer experiments have demonstrated that epigenetic mechanisms operate
      to limit gene expression during animal development. In somatic cells, silenced
      genes are associated with defined chromatin states which are characterised by
      hypermethylation of DNA, hypoacetylation of histones and specific patterns of
      methylation at distinct residues of the N-terminal tails of histone H3 and H4.
      This review describes the role of the DNA methylation-mediated repression system
      (Dnmt1's, MeCPs and MBDs and associated chromatin remodelling activities) in
      animal development. DNA methylation is essential for normal vertebrate
      development but has distinct regulatory roles in non-mammalian and mammalian
      vertebrates. In mammals, DNA methylation has an additional role in regulating
      imprinting. This suggests that epigenetic regulation is plastic in its
      application and should be considered in a developmental context that may be
      species specific.

PMID- 12524009
TI  - Position-effect variegation and the genetic dissection of chromatin regulation in
      Drosophila.
AB  - In position-effect variegation (PEV) genes become silenced by
      heterochromatisation. Genetic dissection of this process has been performed by
      means of dominant suppressor [Su(var)] and enhancer [E(var)] mutations. Selective
      genetic screens allowed mass isolation of more than 380 PEV modifier mutations
      identifying about 150 genes. Genetic fine structure studies revealed unique
      dosage dependent effects. Most of the haplo-dependent Su(var) and E(var) genes do
      not display triplo-dependent effects. Several Su(var) loci with triplo-dependent
      opposite enhancer effects have been identified and shown to encode
      heterochromatin-associated proteins. From these the evolutionary conserved
      histone H3 lysine 9 methyltransferase SU(VAR)3-9 plays a central role in
      heterochromatic gene silencing. Molecular function of most PEV modifier genes is
      still unknown also including genes identified with mutations displaying lethal
      interaction to heterochromatin. Their analysis should contribute to further
      understanding of processes connected with regulation of higher order chromatin
      structure and epigenetic programming.

PMID- 12524010
TI  - Diverse functions of Polycomb group proteins during plant development.
AB  - Polycomb group (PcG) proteins play essential roles in animal and plant life
      cycles by controlling the expression of important developmental regulators. These
      structurally heterogeneous proteins form multimeric protein complexes that
      control higher order chromatin structure and, thereby, the expression state of
      their target genes. Once established, PcG proteins maintain silent gene
      expression states over many cell divisions providing a molecular basis for a
      cellular 'memory.' PcG proteins are best known for their role in the control of
      homeotic genes in Drosophila and mammals. In addition, they play important roles
      in the control of cell proliferation in vertebrate and invertebrate systems.
      Recent studies in plants have shown that PcG proteins regulate diverse
      developmental processes and, as in animals, they affect both homeotic gene
      expression and cell proliferation. Thus, the function of PcG proteins has been
      widely conserved between the plant and animal kingdoms.

PMID- 12524011
TI  - Multiple elements within the Xic regulate random X inactivation in mice.
AB  - In female mammals, the majority of the genes on one of the two X-chromosomes are
      silenced by a process referred to as X-chromosome inactivation. The X
      inactivation center (Xic), a complex genomic region on the X-chromosome which
      controls this process, contains the Xist gene encoding an untranslated RNA which
      plays a central role in the establishment of the transcriptional repression. The
      Xic encrypts a sophisticated program which coordinates X inactivation with sex
      and embryonic development. The present article reviews our current knowledge of
      the regulatory elements lying within the mouse Xic and of the mechanisms
      underlying random X inactivation.

PMID- 12524012
TI  - Epigenetic reprogramming in early mammalian development and following somatic
      nuclear transfer.
AB  - Epigenetic modifications of the genome play a significant role in the elaboration
      of the genetic code as established at fertilisation. These modifications affect
      early growth and development through their influence on gene expression
      especially on imprinted genes. Genome-wide epigenetic reprogramming in germ cells
      is essential in order to reset the parent-of-origin specific marking of imprinted
      genes, but may have a more general role in the restoration of totipotency in the
      early embryo. In a similar way, on somatic nuclear cloning, a differentiated cell
      must become 'reprogrammed' restoring totipotency in order to undergo development.
      Here we discuss the dynamic epigenetic reprogramming that takes place during
      normal development and highlight those areas with relevance to somatic nuclear
      cloning and the possibility of improving the efficiency of this process. We
      propose the concept of 'epigenetic checkpoints' for normal progression of
      development and the loss of totipotency.

PMID- 12524013
TI  - Imprinting and disease.
AB  - Deregulation of imprinted genes has been observed in a number of human diseases
      such as Beckwith-Wiedemann syndrome, Prader-Willi/Angelman syndromes and cancer.
      Imprinting diseases are characterised by complex patterns of mutations and
      associated phenotypes affecting pre- and postnatal growth and neurological
      functions. Regulation of imprinted gene expression is mediated by allele-specific
      epigenetic modifications of DNA and chromatin. These modifications preferentially
      affect central regulatory elements that control in cis over long distances allele
      specific expression of several neighbouring genes. Investigations of imprinting
      diseases have a strong impact on biomedical research and provide interesting
      models for function and mechanisms of epigenetic gene control.

PMID- 12524014
TI  - Retinoid metabolism (LRAT, REH) in the yolk-sac membrane of Japanese quail eggs
      and effects of mono-ortho-PCBs.
AB  - Retinoids stored in the avian egg are essential for normal development, however,
      laboratory and field experiments suggest that they are affected by environmental
      contaminants. Lecithin:retinol acyltransferase (LRAT) activity was detected in
      the microsomal fraction of the yolk-sac membrane of the Japanese quail at day 6
      of development. LRAT activity was maximal at pH 7.0 having apparent kinetic
      parameters of K(m)=1.35 microM and V(max)=0.21 nmol/mg protein/h and was
      inhibited by the sulfhydryl modifying agent N-ethyl-maleimide. Retinol ester
      hydrolase (REH) activity in the microsomal fraction of the yolk-sac membrane was
      stimulated by the bile salt analogue 3-[(3-cholamidopropyl) dimethyl-ammonio]-1
      propane sulfonate and was maximal at pH 9.0 with apparent K(m)=77 microM and
      V(max)=34.3 nmol/mg protein/h. Injection of the PCB congener 2,3,3',4,4'
      pentachlorobiphenyl increased both REH and LRAT activities, whereas 2,3,3',4
      tetrachlorobiphenyl stimulated LRAT. Yolk retinol concentration and the molar
      ratio retinol:retinyl palmitate were lower in the exposed eggs. Yolk retinol
      concentration decreased as LRAT increased (R(2)=0.89) suggesting that certain PCB
      congeners may affect vitamin A mobilization in ovo by increasing LRAT activity in
      the yolk-sac membrane.

PMID- 12524015
TI  - Comparative pharmacokinetics of three non-steroidal anti-inflammatory drugs in
      five bird species.
AB  - Information on the pharmacokinetics and pharmacodynamics of anti-inflammatory
      drugs in birds is scarce. Choice of drug and of dosage is usually empirical,
      since studies of anti-inflammatory drugs are lacking. In this study, three common
      veterinary non-steroidal anti-inflammatory drugs (NSAIDs) were administered
      intravenously to five different bird species. Sodium salicylate, flunixin and
      meloxicam were selected as anti-inflammatory drugs. These NSAIDs were
      administered intravenously to chickens (Gallus gallus), ostriches (Struthio
      camelus), ducks (Anas platyrhynchos), turkeys (Meleagris gallopavo) and pigeons
      (Columba livia). Plasma concentrations of the drugs were determined by validated
      high-performance liquid chromatography methods and pharmacokinetic parameters
      were calculated. Most bird species exhibited rapid elimination of these drugs.
      Ostriches had the fastest elimination rate for all three NSAIDs, but there were
      some interesting species differences. Chickens had a half-life that was
      approximately 10-fold as long as the other bird species for flunixin. The half
      life of chickens and pigeons was three-fold as long as the other bird species for
      meloxicam, and, for salicylic acid, the half-life in pigeons was at least three
      five-fold longer than in the other bird species.

PMID- 12524016
TI  - Endothelin-1 receptor subtypes expression and binding in a perfused rat model of
      myocardial infarction.
AB  - Endothelin-1 (ET-1) pathophysiologic actions are mediated via binding with two
      receptor subtypes, ET(A) and ET(B). Release of ET-1 from endocardial endothelial
      cells and cardiac myocytes can modulate heart tissue necrosis and alterations.
      This study investigates the remodeling processes in Sprague-Dawley rats of
      myocardial infarction (MI) induced by ligating the left anterior descending
      coronary artery. Histological studies were done on cell type distribution using
      cell specific markers and Western blot analysis to localize ET-1 receptor
      subtypes and assess their expression post-MI. In addition, the binding kinetics
      of ET-1 with its receptors in heart perfusion, inlet via the aortic lumen and
      effluent outlet via the right atrium, between two animal model-subgroups were
      done: (1) sham-operated, and sham-operated-CHAPS (3-[(3-cholamidopropyl)
      dimethylammonio]-1-propanesulfonate)-treated; and (2) MI-operated, and MI
      operated-CHAPS-treated. Effluent ET-1 concentration was plotted vs. time using a
      physical model for 1:1 ligand-receptor binding at coronary endothelium and
      myocytes. First order impulse function was used to calculate the affinity
      constants. In MI hearts, fluorescence activity increased for ET(A) vs. ET(B)
      across areas of the muscle compared to normal hearts. Western blotting showed
      upregulation of ET(A) and ET(B) receptors in MI compared with normal hearts.
      Results of ET-1 binding affinity post-MI indicated drastic reduction in spite the
      upregulation of ET(B) on coronary endothelium. Furthermore, substantial affinity
      increase was observed between ET-1 binding with ET(A) at the myocyte site. These
      findings stipulate that during 1 month post-MI some biochemical and hormonal
      effects could alter ET-1 receptor subtype(s) regulation and pharmacodynamics thus
      predisposing to cardiac hypertrophy and mitogenesis.

PMID- 12524017
TI  - Effects of octylphenol and 17beta-estradiol on the gonads of guppies (Poecilia
      reticulata) exposed as adults via the water or as embryos via the mother.
AB  - Endocrine disrupting alkylphenolic compounds have been found in the aquatic
      environment, and concern has arisen over the ability of these compounds to affect
      the reproductive system of fish. In this study, the effects of exposure to an
      environmentally relevant concentration of octylphenol or 17beta-estradiol on the
      gonad structure of fish were examined. Viviparous guppies (Poecilia reticulata)
      were exposed as adults via the water or as embryos via the mother to 26 microg/l
      octylphenol or 0.85 microg/l 17beta-estradiol (mean measured water
      concentrations). Histological examinations revealed effects of the exposures on
      the gonads of the fish exposed as adults. Indications of blocked spermatogonial
      mitosis were seen in the testis structure of adult males after exposure to
      octylphenol or 17beta-estradiol. The post-parturition ovaries of adult females
      exposed to 17beta-estradiol showed effects suggesting an inhibited yolk
      deposition. At the tested concentrations, exposure to octylphenol or 17beta
      estradiol via the mother fish did not significantly affect the weight, length,
      gonopodium index or sex distribution of the offspring. However, histology
      revealed effects on the liver structure, suggesting some effect of maternal
      exposure to octylphenol or 17beta-estradiol. These findings indicate that
      although octylphenol and 17beta-estradiol affect the gonad structure of adult
      male and female guppies, these substances have no significant effects on the
      sexual differentiation of the embryos at the tested concentrations.

PMID- 12524018
TI  - Uptake and clearance of PCB congeners in Chamaelea gallina: response of oxidative
      stress biomarkers.
AB  - PCB uptake and clearance by clams, Chamaelea gallina, were studied in specially
      designed flow-through channels. After 8 weeks exposure to 10 ppb Aroclor 1254 in
      water, clams were depurated for 10 weeks, in the same exposure channel or after
      transfer to clean systems. Accumulation of the 20 congeners studied depended on
      its initial abundance and physicochemical properties. A linear relationship was
      found between log bioconcentration factor and log octanol/water partition
      coefficient of each form. Clearance of each PCB depended also on its initial load
      and solubility, being faster in clams transferred to clean systems. Exposure
      significantly enhanced catalase and 6-P-gluconate dehydrogenase activities, but
      not other antioxidative enzymes. Superoxide dismutase, low during the exposure
      phase, increased seven-fold during depuration. Aroclor-treated clams had higher
      GSH levels than controls, but decreased to 15-35% after 2 days clearance, rose to
      150% after 12 days, and declined to low levels by the end of the experience.
      Biotransformation of PCBs to quinones and redox cycling-promoted oxidative stress
      might explain the increased antioxidative defenses. The biochemical changes
      observed at the beginning of clearance could be attributed to clam handling, by
      adaptation to and recovery from hypoxic/anoxic stress.

PMID- 12524019
TI  - Cytochrome P450 enzyme activity in five herbivorous, non-passerine bird species.
AB  - We examined hepatic cytochrome P450 activity in wild and hand-reared grey
      partridges (Perdix perdix), capercaillies (Tetrao urogallus) and ring-necked
      pheasants (Phasianus colchicus), as well as the enzyme activity in a variety of
      tissues of hand-reared Japanese quails (Coturnix coturnix japonica) and pigeons
      (Columba livia). Post-mortem decrease in hepatic enzyme activity in the grey
      partridge was measured. Hepatic 7-ethoxyresorufin-O-deethylase activity was
      similar in wild and hand-reared grey partridges and pheasants, but the activity
      was significantly lower in wild than in hand-reared capercaillies, probably
      resulting from their phenolic-rich diet. In the tissues of both quails and
      pigeons 7-ethoxycoumarin-O-deethylase exhibited the highest and 7
      pentoxyresorufin-O-deethylase the lowest activity. Hepatic enzyme activity was
      significantly higher than that in other tissues. In the small intestine some
      activity could be found, reflecting some intestinal detoxication capacity. Enzyme
      activity decreased by 34-69% during the 30-min sampling period, which confirmed
      the importance of equalising sampling time to obtain comparable data. Because the
      hand-reared birds in this study were fed the same commercial diets, we assumed
      that the enzyme activity values detected reflect species differences without any
      induction by dietary secondary compounds.

PMID- 12524020
TI  - Production of reactive oxygen species by isolated mitochondria of the Antarctic
      bivalve Laternula elliptica (King and Broderip) under heat stress.
AB  - Formation of reactive oxygen species (ROS) in mitochondrial isolates from gill
      tissues of the Antarctic polar bivalve Laternula elliptica was measured
      fluorimetrically under in vitro conditions. When compared to the rates measured
      at habitat temperature (1 degrees C), significantly elevated ROS formation was
      found under temperature stress of 7 degrees C and higher. ROS formation
      correlated significantly with oxygen consumption in individual mitochondrial
      preparations over the entire range of experimental temperatures (1-12 degrees C).
      ROS generation per mg of mitochondrial protein was significantly higher in state
      3 at maximal respiration and coupling to energy conservation, than in state 4+,
      where ATPase-activity is inhibited by oligomycin and only proton leakage is
      driving the residual oxygen consumption. The percent conversion of oxygen to the
      membrane permeant hydrogen peroxide amounted to 3.7% (state 3) and 6.5% (state
      4+) at habitat temperature (1 degrees C), and to 7% (state 3) and 7.6% (state 4+)
      under experimental warming to 7 degrees C. This is high compared to 1-3% oxygen
      to ROS conversion in mammalian mitochondrial isolates and speaks for a
      comparatively low control of toxic oxygen formation in mitochondria of the polar
      bivalve. However, low metabolic rates at cold Antarctic temperatures keep
      absolute rates of mitochondrial ROS production low and control oxidative stress
      at habitat temperatures. Mitochondrial coupling started to fall beyond 3 degrees
      C, closely to pejus temperature (4 degrees C) of the bivalve. Accordingly, the
      proportion of state 4 respiration increased from below 30% at 1 degrees C to over
      50% of total oxygen consumption at 7 degrees C, entailing reduced ADP/O ratios
      under experimental warming. Progressive mitochondrial uncoupling and formation of
      hazardous ROS contribute to bias mitochondrial functioning under temperature
      stress in vitro. Deduced from a pejus temperature, heat stress commences already
      at 5 degrees C, and is linked to progressive loss of phosphorylation efficiency,
      increased mitochondrial oxygen demand and elevated oxidative stress above pejus
      temperatures.

PMID- 12524021
TI  - Functional identification of epithelial and smooth muscle histamine-dependent
      relaxing mechanisms in the bovine trachea, but not in bronchi.
AB  - Theoretically, the overall effect of histamine on respiratory smooth muscle is
      the result of a subtle balance of contraction and relaxation. The aim of the
      study was to identify histamine type 2 (H2) and 3 (H3) receptor-dependent
      relaxing mechanisms in the contractile elements of the bovine tracheobronchial
      tree. In bronchial preparations, histamine induced very weak contractions, which
      were not exacerbated with the H2-antagonist cimetidine. Moreover, precontracted
      bronchial rings never relaxed in response to cumulative doses of histamine or
      amthamine (H2-agonist). In intact tracheal preparations, histamine induced strong
      contractions that were exacerbated by cimetidine (E(max): +17.2+/-6.6%) but not
      by thioperamide (H3-antagonist). Precontracted tracheal bundles did not relax in
      response to cumulative doses of the H3-agonist R-alpha-methylhistamine. The
      tracheal contractile response was higher in denuded compared to intact
      preparations (11.0+/-1.2 vs. 6.0+/-1.7 g). Cimetidine effect was dramatically
      potentiated in denuded tracheal strips (+40.0+/-11.7%). It is concluded that the
      weak response of bovine bronchi to histamine is due to a relative scarcity of H1
      receptors on bronchial smooth muscle rather than to H2- or H3-dependent
      relaxation. In the bovine trachea, the smooth muscle possesses relaxing H2 but no
      H3 receptors. The epithelium exercises a relaxation, which is independent from H2
      and H3 receptors.

PMID- 12524022
TI  - Purification and characterization of a copper-binding protein from Asian
      periwinkle Littorina brevicula.
AB  - The Asian periwinkle, Littorina brevicula, is highly resistant to a wide range of
      heavy metal concentrations and its metal-binding protein(s) are induced in the
      presence of cadmium (Cd) and zinc (Zn). In this study, we isolated and
      characterized a novel copper-binding protein (Cu-BP). Following purification by
      Sephacryl S-100 chromatography, Cu-BP contained an equal amount of Zn in non
      exposed physiological conditions. However, Zn is replaced by Cu at the binding
      site upon addition of excess Cu (100 microM CuCl(2)) to the cytosol or after a
      long period (60 days) of exposure of the periwinkles to the metal ion (150
      microg/l CuCl(2)). The ligand was further purified by DEAE-Sepharose anion
      exchange chromatography and C(18) reverse-phase HPLC. The molecular weight of the
      purified protein was determined as 11.38 kDa by MALDI-TOF MS analyses. This Cu-BP
      is distinct from common mollusk metallothionein (MT) in that it contains
      significantly lower number of Cys (8 residues) and high levels of aromatic amino
      acids, Tyr and Phe. The protein additionally contains His and Met, which are
      absent in the MT-like Cd-BP of L. brevicula. The finding that Cu-BP in the Asian
      periwinkle is distinct from MT-like Cd-BP suggests that the timely expression of
      specific metal-binding proteins allows added protection against each heavy metal
      in severely polluted conditions.

PMID- 12524024
TI  - In vitro succinylcholine hydrolysis in plasma of the African elephant (Loxodonta
      africana) and impala (Aepyceros melampus).
AB  - In elephants the time lapsed from i.m. injection of an overdose of the muscle
      relaxant succinylcholine (SuCh) until death, is significantly longer than in
      impala. To determine a difference in the rate of SuCh hydrolysis, once the drug
      enters the circulation, contributes to this phenomenon we have measured the rate
      of hydrolysis of SuCh in elephant and impala plasma, and by elephant
      erythrocytes. Rate of hydrolysis was determined by incubating SuCh in plasma or
      erythrocyte lysate at 37 degrees C and quantifying the choline produced. Plasma
      SuCh hydrolytic activity in elephant plasma (12.1+/-1.7 Ul(-1) mean+/-S.D.; n=9)
      was significantly higher than it was in impala plasma (6.6+/-0.6 Ul(-1); n=5),
      but were approximately 12 and 21 times lower, respectively, than in human plasma.
      Elephant erythrocyte lysate had no SuCh hydrolytic activity. Applying this data
      to previous studies, we can show that the ratio of SuCh absorption to SuCh
      hydrolysis is expected to be 1.25:1 and 1.41:1 for elephants and impala
      respectively. It will thus take at least 1.7 times longer for elephant to achieve
      a plasma SuCh concentration similar to that in impala. We conclude that a more
      rapid hydrolysis of SuCh in elephant plasma is one factor that contributes to the
      longer time to death compared to impala.

PMID- 12524023
TI  - Toxicity of cypermethrin in Labeo rohita fingerlings: biochemical, enzymatic and
      haematological consequences.
AB  - The effect of exposure to sub-lethal concentrations of cypermethrin, a synthetic
      pyrethroid pesticide, on biochemical parameters of muscle, blood and enzyme
      activities in brain, liver and kidney of the Indian major carp, Labeo rohita was
      studied. The sub-lethal exposure studies were done for up to 45 days at 1/10 and
      1/50 of 96 h LC(50) of cypermethrin. The 96 h LC(50) was found to be 0.139 ppm.
      RNA levels decreased while DNA levels were elevated. Acid phosphatase was
      unchanged while alkaline phosphatase was depleted. Brain acetylcholinesterase
      activity was decreased significantly (P<0.05) over a period of 45 days at both
      cypermethrin concentrations. Lactate dehydrogenase activity in brain and liver
      was elevated, but inhibited in kidney. Succinate dehydrogenase and ATPase
      activities were depleted in brain, kidney and liver. There was a decrease in
      serum protein level over control at both concentrations of the pyrethroid. Blood
      glucose level and total leucocytes were elevated compared with controls at either
      concentration from day 15 to day 45. Haemoglobin percentage and total
      erythrocytes decreased in both sub-lethal concentrations. Extracts of the herb
      Datura stramonium were effective in countering the toxicity of this pesticide.
      Our data suggest that sub-lethal exposure of cypermethrin alters the biochemical,
      haematological parameters and enzymes of organs tissue and exert stress on the
      fish. Plant extracts may be useful in counteracting some of these effects.

PMID- 12524025
TI  - A new metallothionein gene from the giant keyhole limpet Megathura crenulata.
AB  - Metallothioneins (MTs) are small soluble proteins ubiquitously expressed in
      animals and plants. Different isoforms are present in deuterostomes and
      protostomes. They do not differ greatly in primary structure, but are clearly
      distinguishable. Here, I present the gene and the complete cDNA of a novel MT
      from the mollusk Megathura crenulata. This protein is closely related to the Cu
      inducible MTs of the vineyard snail Helix pomatia, but has also some minor
      sequence features typical of Cd-inducible isoforms of H. pomatia and other
      molluscs. Overall, the deduced primary structure is similar to the known
      molluscan MTs, but in addition possesses an insertion of 5 amino acids not found
      in any other molluscan MTs, protostomic or deuterostomic MTs. In addition, a
      pentapeptide insertion, characteristic of mammalian MT-3 is present but it lacks
      the functional tetrapeptide CPCP within the beta-region of those MT-3 proteins
      that are known to suppress neuronal growth processes. The M. crenulata MT is a
      novel form of MT in comparison to all other known MTs. Possible functional
      aspects for this new MT are discussed.

PMID- 12524026
TI  - Effect of nitric oxide synthase inhibition on the manipulative behaviour of Sepia
      officinalis.
AB  - Nitric oxide (NO), produced by nitric oxide synthase (NOS) in brain tissue, is
      essential for a variety of kinds of learning in vertebrates. In invertebrates,
      there are clear examples of an association between NO signalling and olfaction,
      feeding behaviour and learning. The role of NO as a neurotransmitter in the
      manipulative behaviour of Sepia officinalis was tested. Manipulative behaviour
      requires extensive chemotactile sensory processing, fine motor control and
      probably motor learning processes. NADPH-diaphorase activity (a reliable
      histochemical marker for nitric oxide synthase) was found in sensory epithelia
      and in the axial nerve cord of the arms. NOS inhibitor injections (L-NAME)
      produced an increase in the latency of prey paralysis. By placing mechanical
      constraints on the base of the fifth periopods of the crab, we prevented the
      cuttlefish from injecting cephalotoxin and, thus, forced it to change injection
      sites. We showed that L-NAME pretreatment did not affect the flexibility of the
      manipulative behaviour. The implications of the involvement of NO in the
      acquisition of chemo-tactile information and in the programming of the motor
      skills of the manipulative behaviour is discussed.

PMID- 12524027
TI  - Mercury and non-protein thiol compounds in the seagrass Posidonia oceanica.
AB  - Mercury concentrations, non-protein thiol levels and the enzyme activities of
      glutathione-S-transferase (GST) were measured in the blades and sheaths of the
      marine phanerogam Posidonia oceanica. The seagrass was collected in January and
      June and at three sites: the Bay of Rosignano (Italy) known for its mercury
      contamination, the north of the Lerins islands (Bay of Cannes, France), the Bay
      of Tonnara (Corsica, France). The two latter sites are considered as free of any
      known industrial inputs. Mercury concentrations and GST activities in both
      tissues were always higher in samples from Rosignano, particularly in June. Non
      protein thiol levels were significantly higher in the blades than in the sheaths
      of P. oceanica from Tonnara and Lerins. In contrast, at Rosignano, the sheaths
      presented a significantly higher non-protein thiol concentration than the blades,
      particularly in June. Levels in the sheaths appeared to increase with the degree
      of pollution. Western Blot performed on sheaths of P. oceanica collected in June
      at Rosignano and Lerins revealed a characteristic band of GSTs at 31 kDa, proving
      the presence of the GST enzyme in this tissue. Mercury seemed to exert an
      influence upon non-protein thiol metabolism, including GST induction, in P.
      oceanica collected from the NW Mediterranean.

PMID- 12524028
TI  - Costs of gestation in an Arctic ruminant: copper reserves in muskoxen.
AB  - The transfer of trace minerals between mother and fetus may be critical for
      survival of young ruminants especially among species at high latitudes, which
      gestate during a long winter and grow through a brief summer. We examined the
      distribution of copper and metalloproteins (ceruloplasmin and metallothionein) in
      muskoxen and their fetuses, three times during gestation. Hepatic levels of
      copper were high in mothers (179 microg g(-1) whole tissue) and did not change
      through gestation, whereas fetuses accumulated large reserves of Cu (>300 microg
      g(-1)), likely stored in proteins such as metallothionein, during the last third
      of gestation. The effect of fetal Cu demands on the pregnant female was tested by
      supplementation of Cu by subcutaneous injections of Cu gluconate (30 mg Cu/week)
      during pregnancy. Maternal copper supplementation did not significantly increase
      hepatic Cu in newborns (412 microg g(-1) for supplemented vs. 303 microg g(-1)
      for unsupplemented neonates), probably because the diet was already adequate in
      copper (14 microg g(-1) dry matter). Ceruloplasmin activity declined in pregnant
      muskoxen that had not received injections of Cu and suggested increased systemic
      demands for copper during late gestation. Supplies of Cu to the fetus could be
      limited either by low levels of Cu in the maternal liver, or in the maternal diet
      during late winter when fetal gains in mass and liver Cu are greatest.

PMID- 12524030
TI  - A novel view on the mechanisms of action of insulin and other insulin superfamily
      peptides: involvement of adenylyl cyclase signaling system.
AB  - A new signaling mechanism common to mammalian insulin, insulin-like growth factor
      I, relaxin and mollusc insulin-like peptide, and involving receptor-tyrosine
      kinase==>G(i) protein (betagamma)==>phosphatidylinositol-3-kinase==>protein
      kinase Czeta==>adenylyl cyclase==>protein kinase A was discovered in the muscles
      and some other tissues of vertebrates and invertebrates. The authors' data were
      used to reconsider the problem of participation of the adenylyl cyclase-cAMP
      system in the regulatory effects of insulin superfamily peptides. A hypothesis
      has been put forward according to which the adenylyl cyclase signaling mechanism
      producing cAMP has a triple co-ordinating role in the regulatory action of
      insulin superfamily peptides on the main cell processes, inducing the mitogenic
      and antiapoptotic effects and inhibitory influence on some metabolic effects of
      the peptides. It is suggested that cAMP is a key regulator responsible for
      choosing the transduction pathway by concerted launching of one (proliferative)
      program and switching off (suppression) of two others, which lead to cell death
      and to the predomination of anabolic processes in a cell. The original data
      obtained give grounds to conclude that the adenylyl cyclase signaling system is a
      mechanism of signal transduction not only of hormones with serpentine receptors,
      but also of those with receptors of the tyrosine kinase type (insulin superfamily
      peptides and some growth factors).

PMID- 12524029
TI  - Xenobiotic conjugation systems in deer compared with cattle and rat.
AB  - The ability of cattle and deer liver to catalyse xenobiotic conjugation reactions
      was investigated and compared with that of the rat. Marked differences in the
      activity of these enzymes were noted between the domestic animals and rats.
      Hepatic microsomal epoxide hydrolase activity in cattle and deer, determined
      using benzo[a]pyrene 4,5-oxide as substrate, was nearly twice that of the rat. In
      contrast, glutathione S-transferase activity in hepatic cytosol, determined with
      1-chloro-2,4-dinitrobenzene as substrate, was significantly lower in the cattle
      and deer. When 1,2-dichloro-4-nitrobenzene served as the accepting substrate, no
      activity was detectable in the cattle and deer. Similarly, glutathione reductase
      activity and total glutathione levels were markedly lower in the cattle and deer
      compared with the rat. Cytosolic sulfotransferase activity, monitored using 2
      naphthol as substrate, was higher in cattle compared with the rat. Finally,
      microsomal UDP-glucuronosyl transferase activity, determined using 1-napththol as
      substrate, did not differ significantly among the three species.

PMID- 12524031
TI  - Molecular cloning and characterisation of peroxisome proliferator activated
      receptor gamma1 (PPARgamma1) cDNA gene from guinea pig (Cavia porcellus): tissue
      distribution.
AB  - The coding region of guinea pig peroxisome proliferator activated receptor gamma1
      (gpPPARgamma1) cDNA was successfully cloned from adipose tissue by reverse
      transcription polymerase chain reaction (RT-PCR) using the designated primers
      based on the conserved regions of the other mammalian PPARgamma1 sequence. From
      RT-PCR, a combination of three cDNA fragments that comprised of the full length
      coding region PPARgamma1 cDNA gene were amplified, with the size of 498, 550 and
      557 bp, respectively. All three fragments were then successfully assembled by
      utilising the internal restriction sites present at the overlapping regions to
      give rise to the full-length coding region of gpPPARgamma1 with the size of 1428
      bp and consisting of 475 amino acids. Guinea pig PPARgamma1 is highly conserved
      with those of other species at protein and nucleotide levels. Gene expression
      studies showed that gpPPARgamma mRNA was predominantly expressed in adipose
      tissue followed by lung and spleen. However, at the protein level, PPARgamma was
      also found to be expressed in skeletal muscle.

PMID- 12524032
TI  - Purification and characterization of a fibrinolytic enzyme produced by Bacillus
      amyloliquefaciens DC-4 screened from douchi, a traditional Chinese soybean food.
AB  - Bacillus amyloliquefaciens DC-4, which produces a strongly fibrinolytic enzyme,
      was isolated from douchi, a traditional Chinese soybean-fermented food. A
      fibrinolytic enzyme (subtilisin DFE) was purified from the supernatant of B.
      amyloliquefaciens DC-4 culture broth and displayed thermophilic, hydrophilic and
      strong fibrinolytic activity. Subtilisin DFE was demonstrated to be homogeneous
      by SDS-PAGE and isoelectric focusing electrophoresis, and has molecular mass of
      28000 Da and a pI of 8.0. The optimal reaction pH value and temperature were 9.0
      and 48 degrees C, respectively. Subtilisin DFE not only hydrolyzed fibrin but
      also several synthetic substrates, particularly Suc-Ala-Ala-Pro-Phe-pNA, and
      phenylmethylsulfony fluoride can completely inhibit its fibrinolytic activity.
      These results indicated that subtilisin DFE is a subtilisin-family serine
      protease, similar to nattokinase from Bacillus natto. The first 24 amino acid
      residues of the N-terminal sequence of subtilisin DFE were
      AQSVPYGVSQIKAPALHSQGFTGS, which is identical to that of subtilisin K-54, and
      different from that of NK and CK. Results from subtilisin DFE gene sequence
      analysis showed that subtilisin DFE is a novel fibrinolytic enzyme.

PMID- 12524033
TI  - Whale (Balaenoptera physalus) haemoglobin: primary structure, functional
      characterisation and computer modelling studies.
AB  - The functional properties of haemoglobin from the Mediterranean whale
      Balaenoptera physalus have been studied as functions of heterotropic effector
      concentration and temperature. Particular attention has been given to the effect
      of carbon dioxide and lactate since the animal is specialised for prolonged dives
      often in cold water. The molecular basis of the functional behaviour and in
      particular of the weak interaction with 2,3-diphosphoglycerate is discussed in
      the light of the primary structure and of computer modelling. On these bases, it
      is suggested that the A2 (Pro-->Ala) substitution observed in the beta chains of
      whale haemoglobin may be responsible for the displacement of the A helix known to
      be a key structural feature in haemoglobins that display an altered interaction
      with 2,3-diphosphoglycerate as compared with human haemoglobin. The functional
      and structural results, discussed in the light of a previous study on the
      haemoglobin from the Arctic whale Balaenoptera acutorostrata, give further
      insights into the regulatory mechanisms of the interactive effects of
      temperature, carbon dioxide and lactate.

PMID- 12524034
TI  - Magnesium and phosphorus distribution in the avian eggshell.
AB  - Magnesium and phosphorus are major inorganic constituents of the avian eggshell.
      The Mg/Ca ratio has been used as a palaeothermometer in a range of calcite
      biominerals. Eggshells provide the opportunity to examine the Mg/Ca ratio of a
      calcite biomineral produced in a constant temperature environment. Mg
      distribution is not constant throughout the shell, decreasing from nucleation
      until after fusion of the mammillary caps and then increasing to termination.
      This indicates that temperature of deposition is not the only factor controlling
      the Mg content of this biomineral system. There is a greater increase in
      magnesium concentration in the outer region of eggshells from older birds. The
      variation in magnesium concentration does not appear to correlate with organic
      content. Phosphorus occurs in the outer quarter of the eggshell and rises to
      termination and is therefore not confined to cuticular vesicles.

PMID- 12524035
TI  - Molecular identification of uncoupling proteins (UCP2 and UCP3) and absence of
      UCP1 in the marsupial Tasmanian bettong, Bettongia gaimardi.
AB  - This study has identified the expression of uncoupling proteins in a marsupial
      using molecular techniques. The Tasmanian bettong, Bettongia gaimardi, increases
      non-shivering thermogenesis (NST) in response to cold exposure and
      norepinephrine, although previous studies have been unable to demonstrate the
      presence of brown adipose tissue or uncoupling protein 1 (UCP1). This study used
      molecular techniques to confirm the absence of UCP1 as well as ascertain if this
      species expresses UCP2 and/or UCP3. Tissue samples from four B. gaimardi were
      taken prior to and post-cold exposure at 4-5 degrees C for 2 weeks. The tissues
      were then examined for UCP1, UCP2 and UCP3 expression using Western blotting.
      UCP2 and UCP3 were amplified through RT-PCR and subsequently sequenced to confirm
      molecular identity. Our work confirms that B. gaimardi does not express UCP1 and
      that this species expresses both uncoupling proteins 2 and 3. The sequencing of
      the amplified B. gaimardi UCP2 and UCP3 cDNAs have revealed a 74% homology with
      rat UCP2 cDNA, and 65% homology with rat UCP3 cDNA. Although this work has not
      yet characterised the functional properties of these proteins in the marsupial,
      it does suggest a possible mechanism to explain the existence of NST in B.
      gaimardi.

PMID- 12524036
TI  - N-methyl-D-glutamate and N-methyl-L-glutamate in Scapharca broughtonii (Mollusca)
      and other invertebrates.
AB  - The presence of N-methyl-D-glutamate (NMDG) and N-methyl-L-glutamate (NMLG) has
      been demonstrated in the tissues of Scapharca broughtonii, which are known to
      contain N-methyl-D-aspartate (NMDA). To our knowledge, this is the first report
      on the natural occurrence of NMDG and the occurrence of NMLG in eukaryotes. These
      compounds were identified according to the following findings; (a) their
      derivatives with (+)- and (-)-l-(9-fluorenyl)ethyl chloroformate (FLEC) showed
      identical behaviors with those of authentic NMDG and NMLA, respectively, on high
      performance liquid chromatography (HPLC), (b) the HPLC peak of NMDG disappeared
      when the extract, as well as the authentic compound, was treated with D-aspartate
      oxidase before derivatization, (c) they behaved identically with authentic
      compounds on thin-layer chromatography and differently from NMDA. Both or either
      of NMDG and NMLG were also detected in several mollusks and other animals.
      Concentrations of the enantiomers were comparable in the tissues of S.
      broughtonii and a few other species.

PMID- 12524037
TI  - Isolation and characterization of cytidine-5'-monophosphate-N-acetylneuraminate
      hydroxylase from the starfish Asterias rubens.
AB  - The sialic acid N-glycolylneuraminic acid (Neu5Gc) is formed by cytidine-5'
      monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (EC 1.14.13.45).
      The enzyme from mammals exhibits several unusual characteristics, raising
      questions about its evolution. Since echinoderms are the most primitive organisms
      possessing glycoconjugate-bound Neu5Gc, studies on the hydroxylase from members
      of this phylum may yield insights into the origin and development of the
      hydroxylase. Investigations on crude CMP-Neu5Ac hydroxylase in gonads from the
      starfish Asterias rubens revealed that it shares many properties with its
      mammalian counterpart. However, the echinoderm hydroxylase also exhibits
      fundamental differences, particularly its association with a membrane and a
      requirement for high ionic strength for optimal activity. Here, we describe the
      isolation of the CMP-Neu5Ac hydroxylase from A. rubens gonads using anion
      exchange chromatography and chromatography on immobilized cytochrome b(5). The
      enzyme was enriched 137-fold with a yield of 13%. The preparation exhibited a
      main polypeptide of 76 kDa, consistent with a cDNA sequence published earlier,
      and a minor protein of 64 kDa. A kinetic characterization showed that salt
      activation of this enzyme results from an increase in affinity for CMP-Neu5Ac.
      Evidence for the formation of a ternary complex of hydroxylase, CMP-Neu5Ac and
      cytochrome b(5) is also presented. The mechanistic and physiological significance
      of these results is discussed.

PMID- 12524038
TI  - A new method to estimate the relative bioavailability of individual amino acids
      in fish larvae using 13C-NMR spectroscopy.
AB  - In comparison to mammals, fish, and in particular young stages, are thought to
      have higher amino acid (AA) requirements. Still, little is known about AA
      requirements of fish larvae, largely due to difficulties in applying traditional
      methodologies to these fast growing small animals. This study presents a new
      method to study the qualitative AA requirements of fish larvae. This method
      combines the use of 13C-labelled live food and 13C-NMR spectroscopy. It allows
      the simultaneous estimation of the relative bioavailability of several individual
      AAs. The present study shows that the relative bioavailabilies of various AAs do
      differ between AAs in larval seabream (Sparus aurata). Threonine has a low
      relative bioavailability, while aspartate, glutamate and lysine had high relative
      bioavailabilies compared to other AAs. These results are here attributed to
      differences in absorption rates by the gut, and/or selective catabolism. The
      results from the present study suggest that when rotifers are used as the diet
      for larval seabream, they should be enriched with products rich in threonine and
      leucine. Information on the relative bioavailability of individual AAs together
      with the AA profile of the larval protein should allow defining the ideal dietary
      AA profile for a given species.

PMID- 12524039
TI  - Comparison of fatty acid composition in major lipid classes of the dominant
      benthic invertebrates of the Yenisei river.
AB  - The composition and content of fatty acids (FAs) in total lipids,
      triacylglycerols (TAG) and polar lipids (PL) in dominant groups of benthic
      invertebrates: gammarids (Gammaridae, Amphipoda), chironomid larvae
      (Chironomidae, Diptera), caddisfly larvae (Trichoptera) and mayfly larvae
      (Ephemeroptera) were studied in the Yenisei river. For the first time data on the
      FA composition of species belonging to Trichoptera (Insecta) are presented. The
      groups of aquatic insect larvae and gammarids weakly differed in total content of
      essential polyunsaturated fatty acids (PUFAs). Hence, the strong invasion of
      gammarids which occurred in the last decades in the Yenisei river should not
      result in a decrease in potential yield of essential PUFA in the ecosystem and
      corresponding decrease in food resource quality for fish in respect to PUFA
      content. Significant differences in biomarker FAs in TAG were found which
      correlated to specific food sources. Different levels of long-chain PUFA in PL of
      the invertebrates are discussed in relation to the genetic ability of particular
      taxa to form these FAs.

PMID- 12524040
TI  - Muscle-specific expression of myogenin in zebrafish embryos is controlled by
      multiple regulatory elements in the promoter.
AB  - Myogenin is a member of the basic Helix-Loop-Helix transcription factor family
      that play key roles in myoblast specification and differentiation. Myogenin is
      specifically expressed in developing somite and skeletal muscles in zebrafish
      embryos. To determine the regulation of myogenin expression, we reported here the
      characterization of zebrafish myogenin gene and analysis of its promoter activity
      in zebrafish embryos. Our data showed that a 0.8-kb myogenin promoter was
      sufficient to direct correct temporal and spatial muscle-specific green
      fluorescence protein expression in zebrafish embryos. Sequence analysis
      identified two putative E box sites in the myogenin gene promoter. In addition, a
      MEF2 recognition site and a MEF3 binding site were also found in the promoter.
      Mutation of the E boxes, MEF2 or MEF3 binding site individually had little effect
      on the muscle-specificity and activity of the myogenin promoter. However,
      mutating these sites in various combinations, e.g. E boxes and MEF2 binding site,
      or MEF2 and MEF3 sites significantly reduced the activity of the promoter.
      Moreover, mutating the E boxes, MEF2 and MEF3 sites together almost abolished the
      activity of the promoter. These data indicate that muscle-specific expression of
      myogenin in zebrafish embryos is controlled by multiple regulatory elements in
      the promoter. In addition, because these regulatory elements control myogenin
      expression in mouse and human embryos, these data suggest that the regulatory
      mechanism controlling myogenin expression might be conserved during evolution.

PMID- 12524041
TI  - Hemocyte components in crustaceans convert hemocyanin into a phenoloxidase-like
      enzyme.
AB  - The functional conversion of hemocyanin (Hc), an oxygen transporter, into an
      enzyme was investigated in crustaceans. Hc is converted into a phenoloxidase-like
      enzyme by hemocyte components, which is triggered by beta-1,3-glucan. This
      activation is severely hampered with leupeptin and E-64 treatment, indicating
      that the serine/cysteine proteases in the hemocytes are involved in the
      activation. In a SDS-PAGE-analysis, no change was observed between normal and
      activated Hc under reduced conditions. However, under non-reduced condition of
      normal Hc, several minor bands were observed at oligomeric position of Hc
      subunit, which disappeared upon activation. These results indicate that a split
      of the reductive bond, such as the disulfide bond between subunits, is essential
      for Hc activation. This is the first report to show the enzymatic conversion of
      Hc and the presence of the covalent bond in the Hc subunit of crustaceans.

PMID- 12524042
TI  - Digestive enzymes in juvenile green abalone, Haliotis fulgens, fed natural food.
AB  - Enzymes responsible for the digestion of food protein by juvenile green abalone
      (Haliotis fulgens) were studied when fed algae or a sea grass (Phyllospadix
      torreyi) naturally occurring in the habitat. The effect of food on the
      composition and activity of the enzymes was also evaluated. Acid, serine
      proteinases and aminopeptidases, as confirmed by pH profile of activity, specific
      inhibition and synthetic substrate hydrolysis were found in the digestive organs
      of juvenile green abalone. Algae and sea grass differentially affected the
      digestive system in abalone.

PMID- 12524043
TI  - Purification and partial characterization of feline classical pancreatic lipase.
AB  - Classical pancreatic lipase has been purified and partially characterized in many
      species. The objective of this project was to purify feline classical pancreatic
      lipase (fPL) from pancreatic tissue and partially characterize this protein.
      Pancreata were collected from cats (Felis catus) euthanized for unrelated
      research projects. Fat was removed by trimming away grossly visible fat and by
      extraction in organic solvents. The delipidated pancreatic extract was further
      purified by extracting the enzymes in a Tris-buffer containing two different
      protease inhibitors, benzamidine and phenylmethylsulfonyl fluoride, followed by
      anion-exchange, size-exclusion, and cation-exchange chromatography. Feline
      pancreatic lipase was successfully purified from feline pancreatic tissue. The
      purified product showed a single band on sodium dodecyl sulfate polyacrylamide
      gel electrophoresis with a molecular mass of approximately 52.5 kDa. Exact
      molecular mass was determined by mass spectrometry as 52.4 kDa. Approximate
      specific absorbance at 280 nm of fPL was 1.18 for a 1 mg/ml solution. N-terminal
      amino acid sequence of the first 25 amino acid residues showed the sequence Lys
      Glu-Ile-?-Phe-Pro-Arg-Leu-Gly-?-Phe-Ser-Asp-Asp-Ala-Pro-Trp-Ala-Gly-Ile-Ala-Gln
      Arg-Pro-Leu. This sequence showed close homology with the amino acid sequence of
      classical pancreatic lipase in other species.

PMID- 12524044
TI  - Expression of protein phosphatase 1 during the asexual development of Neurospora
      crassa.
AB  - We cloned and sequenced the cDNA and the gene encoding the catalytic subunit of
      protein phosphatase 1 from the filamentous fungus Neurospora crassa. The gene,
      designated ppp-1 (phosphoprotein phosphatase 1), was mapped by restriction
      fragment length polymorphism to linkage group III, in the vicinity of con-7 and
      trp-1. The expression of the gene was monitored by reverse transcriptase and
      polymerase chain reactions, by Western blotting, and by protein phosphatase
      activity assays in synchronized cultures. Transcripts of ppp-1 were detected in
      the dormant conidia. The abundance of ppp-1 mRNA, Ppp-1 protein, and the activity
      of protein phosphatase 1 increased during germination and subsequent hyphal
      elongation as well as during the early stages of aerial mycelium formation.

PMID- 12524045
TI  - Similarity between the major collagens of cuttlefish cranial cartilage and
      cornea.
AB  - Invertebrates possess unique collagen-containing connective tissue elements, the
      biochemistry of which is not clearly understood. We previously reported the
      occurrence of a novel heterotrimeric type V/XI like collagen in the cranial
      cartilage of the cuttlefish Sepia officinalis. We report here the purification of
      the three chains by ion exchange chromatography and the physicochemical
      characteristics of this collagen. This collagen shared substantial similarity to
      the collagen purified from the cornea of S. officinalis, with respect to chain
      composition, cyanogen bromide peptide profile and amino acid composition. The
      mobility of the C3 chain was retarded in the corneal collagen, which also had an
      increased glycine content and a smaller ratio of hydroxylysine to lysine,
      together with a reduction in bound carbohydrates. The cartilage collagen had a
      higher denaturation temperature than corneal collagen. As observed by
      transmission electron microscopy of reconstituted fibrils, the heterotrimeric
      invertebrate collagen formed fibrils of no apparent periodicities as opposed to
      the regular 64-nm banding pattern of milk shark (Rhizoprionodon acutus) cartilage
      collagen. This is also the first report on the molecular species of collagen in
      an invertebrate cornea. Our results strongly support the functioning of minor
      vertebrate collagens as major collagens in some invertebrates, close similarity
      of collagens in two tissues with different functions and would hold significance
      to our understanding of collagen polymorphism and the evolution of the
      extracellular matrix.

PMID- 12524046
TI  - Activation of the rainbow trout metallothionein-A promoter by silver and zinc.
AB  - In fish, the synthesis of metallothionein (MT) is increased by a number of heavy
      metals. The rainbow trout MT-A gene promoter region contains six known metal
      responsive elements (MREs), that mediate promoter activation by metals. In the
      present study, two fish cell lines differing in their ability to produce MT, RTG
      2 (produce MT protein) and CHSE-214 (produce no detectable MT protein), were used
      to help elucidate the roles of Zn, Ag and MT in the activation of the MT
      promoter. The hypothesis tested was that Ag activates the MT-A promoter
      indirectly by displacing Zn from pre-existing Zn-MT and that this liberated Zn
      subsequently induces MT synthesis. Both cell lines were transfected with a
      luciferase reporter gene construct containing the rainbow trout MT-A promoter,
      exposed to various concentrations of Zn or Ag, and assayed for luciferase
      activity. CHSE-214 cells showed five times greater production of luciferase than
      RTG-2 cells when exposed to identical concentrations of Ag. Thus, Ag can likely
      induce MT transcription without displacing Zn from pre-existing Zn-MT.
      Furthermore, Ag activated the MT promoter at concentrations 100-fold lower than
      those required for Zn to initiate transcription, suggesting that zinc displaced
      from other sites by such low concentrations of Ag would not be sufficient to
      initiate MT transcription. This interpretation was further supported by
      radiotracer studies indicating that Ag did not cause a redistribution of 65Zn
      within either of the two cell types. These combined results indicate that Ag may
      be a direct inducer of MT.

PMID- 12524047
TI  - Turkey intestine as a commercial source of heparin? Comparative structural
      studies of intestinal avian and mammalian glycosaminoglycans.
AB  - Heparin is a glycosaminoglycan (GAG) that is extracted primarily from porcine
      intestinal tissues and is widely used as a clinical anticoagulant. It is
      biosynthesized as a proteoglycan and stored exclusively in mast cells and is
      partially degraded to peptidoglycan and GAG on immunologically activated mast
      cell degranulation. In contrast, the structurally related heparan sulfate, is the
      polysaccharide portion of a ubiquitous proteoglycan, localized on cell surface
      and in the extracellular matrix of all animal tissues. Heparin and heparan
      sulfate are made in the Golgi through a similar biosynthetic pathway. The current
      study was undertaken in a search for alternative, non-mammalian, sources of
      anticoagulant heparin. The heparin/heparan sulfate family of GAGs, prepared and
      purified from turkey intestine, were assayed for anticoagulant activity and
      structurally characterized. The resulting GAGs displayed a very low anticoagulant
      activity when compared to those obtained from porcine intestine using an
      identical procedure. Structural characterization studies clearly demonstrate that
      heparan sulfate is the major GAG in the turkey intestine. This observation is
      rationalized based on differences in the mammalian and avian coagulation and
      immune systems.

PMID- 12524049
TI  - Purification, characterization and cloning of tensilin, the collagen-fibril
      binding and tissue-stiffening factor from Cucumaria frondosa dermis.
AB  - The inner dermis of the sea cucumber, Cucumaria frondosa, is a mutable
      collagenous tissue characterized by rapid and reversible changes in its
      mechanical properties regulated by one or more protein effectors that are
      released from neurosecretory cells. One such effector, tensilin, is a collagen
      fibril binding protein, named for its ability to induce dermis stiffening.
      Tensilin was purified using an affinity column constructed from C. frondosa
      collagen-fibrils. The protein migrates as a single band on SDS-PAGE (Mr
      approximately 33 kDa) and has an isoelectric point of 5.8. Equilibrium
      sedimentation experiments suggest a molecular mass of approximately 28.5-29.4
      kDa. Carbohydrate analysis of tensilin revealed no measurable sugar content. The
      molar amount of tensilin was determined to be 0.38% that of collagen and 47% that
      of stiparin, a constitutive matrix glycoprotein. A full-length cDNA clone for
      tensilin was obtained from a C. frondosa inner dermis cDNA expression library.
      Predicted properties derived from the deduced peptide sequence were in agreement
      with those of the native protein. A noted feature of tensilin's deduced peptide
      sequence, particularly in its N-terminal domain, is its homology to tissue
      inhibitor of metalloproteinases. Tensilin's C-terminal tail has no known homology
      to other proteins but contains a putative collagen-fibril binding site.

PMID- 12524050
TI  - Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development.
AB  - The extracellular glycoproteins fibrillin-1 and fibrillin-2 are major components
      of connective tissue microfibrils. Mutations in the fibrillin-1 and fibrillin-2
      genes are responsible for the phenotypical manifestations of Marfan syndrome and
      congenital contractural arachnodactyly respectively, which emphasizes their
      essential roles in developmental processes of various tissues. Consistent with
      this last notion, organ culture experiments have indirectly suggested morphogenic
      roles for fibrillins in lung and kidney development. In order to contribute to
      the understanding of the roles of fibrillins in developmental and morphogenetic
      events, we have investigated the distribution of fibrillin-1 and fibrillin-2 in
      human embryonic and early fetal tissues between the 5th and the 12th gestational
      week, i.e. at the beginning of organogenesis. Fibrillin-1 and fibrillin-2 were
      localized immunohistochemically using specific monoclonal antibodies, mAb 69 and
      mAb 48, respectively. Both fibrillins are widely distributed in various human
      anlagen, from early developmental stages. In most embryonic and early fetal human
      organs such as skin, lung, heart, aorta, central nervous system anlage, nerves,
      and ganglia, fibrillin-1 and fibrillin-2 follow the same temporo-spatial pattern
      of distribution. However, in other organs such as kidney, liver, rib anlagen,
      notochord fibrillin-1 and fibrillin-2 are distributed differentially. The present
      paper is focused on this aspect. These results suggest different roles for
      fibrillin-1 and -2 in the development of these structures.

PMID- 12524051
TI  - Hierarchical assembly and the onset of banding in fibrous long spacing collagen
      revealed by atomic force microscopy.
AB  - The mechanism of formation of fibrillar collagen with a banding periodicity much
      greater than the 67 nm of native collagen, i.e. the so-called fibrous long
      spacing (FLS) collagen, has been speculated upon, but has not been previously
      studied experimentally from a detailed structural perspective. In vitro, such
      fibrils, with banding periodicity of approximately 270 nm, may be produced by
      dialysis of an acidic solution of type I collagen and alpha(1)-acid glycoprotein
      against deionized water. FLS collagen assembly was investigated by visualization
      of assembly intermediates that were formed during the course of dialysis using
      atomic force microscopy. Below pH 4, thin, curly nonbanded fibrils were formed.
      When the dialysis solution reached approximately pH 4, thin, filamentous
      structures that showed protrusions spaced at approximately 270 nm were seen. As
      the pH increased, these protofibrils appeared to associate loosely into larger
      fibrils with clear approximately 270 nm banding which increased in diameter and
      compactness, such that by approximately pH 4.6, mature FLS collagen fibrils begin
      to be observed with increasing frequency. These results suggest that there are
      aspects of a stepwise process in the formation of FLS collagen, and that the
      banding pattern arises quite early and very specifically in this process. It is
      proposed that typical 4D-period staggered microfibril subunits assemble laterally
      with minimal stagger between adjacent fibrils. alpha(1)-Acid glycoprotein
      presumably promotes this otherwise abnormal lateral assembly over native-type
      self-assembly. Cocoon-like fibrils, which are hundreds of nanometers in diameter
      and 10-20 microm in length, were found to coexist with mature FLS fibrils.

PMID- 12524052
TI  - New technologies in vitro for analysis of cell movement on or within collagen
      gels.
AB  - The movement of cells through extracellular matrix (ECM) is a critical component
      of many normal and pathological processes in vivo. Consequently, efforts to
      characterize motility-associated interactions between cells and ECM have led to
      the development of methods to observe and quantify (assay) the movement of cells
      under simplified conditions in vitro. In this report, we describe a novel method
      (the bullseye assay) and apparatus for the concentration of cells into small,
      precisely sized and shaped circular disks (bullseyes) that serve as starting
      points for migration of cells within ECM. The same apparatus is used to form the
      bullseyes and position them at the center of flat disks (windows) of gelled
      collagen that are supported at the edges by rings of nylon mesh. Complete
      assemblies, each consisting of a bullseye, collagen window and nylon mesh ring,
      are transferred to tissue culture wells for assay of cell migration either within
      or on top of the collagen window. Studies of the migratory responses of three
      different cell types to specific cytokines demonstrated that the bullseye assay
      was sensitive, rapid to set up, and easy to use. In conjunction with the bullseye
      assay, we developed a novel annular grayscale method for quantification of cell
      migration from digital images. The method is easily mastered, is derived from a
      measurement program in the public domain, is not subjective and is more
      discriminative than other techniques of measurement.

PMID- 12524053
TI  - A systematic review of the reproductive system effects of metformin in patients
      with polycystic ovary syndrome.
AB  - OBJECTIVE: To review the effectiveness of metformin in restoring regular
      menstrual cycles and ovulation and achieving pregnancy in women with polycystic
      ovary syndrome (PCOS). DESIGN: Systematic review of pertinent studies identified
      using the bibliographic databases MEDLINE and EMBASE. References of selected
      articles identified were hand-searched for additional relevant citations.
      PATIENT(S): Women with PCOS undergoing treatment with metformin alone, metformin
      combined with other methods of ovulation induction such as clomiphene citrate
      (CC) or gonadotropin injections, or metformin combined with in vitro
      fertilization (IVF). RESULT(S): Thirty published studies were included in the
      overall review. Studies consisted of 12 randomized controlled trials, two cohort
      studies, and 16 uncontrolled descriptive studies. Due to a strong variability in
      the use of metformin according to study population, exposure, and outcome of
      interest, it was not possible to combine the data of the 12 randomized controlled
      trials to perform a meta-analysis. Limited data on predominately obese PCOS
      patients demonstrate that metformin alone improves both restoration of regular
      menses and spontaneous ovulation, but there are no data supporting an improvement
      in pregnancy rate. The addition of metformin to CC results in an improved
      ovulation and pregnancy rate in both unselected and CC-resistant PCOS women.
      There are insufficient data to make any conclusions on the effect of metformin on
      FSH ovulation induction or IVF. CONCLUSION(S): The effectiveness and role of
      metformin in the treatment of PCOS anovulatory infertility in clinical practice
      is difficult to assess from currently available research. Further well-designed
      prospective, perhaps multicenter, randomized controlled trials with the primary
      end point of pregnancy or live-birth rate are required.

PMID- 12524054
TI  - A year of inaction on high-order multiple pregnancies due to ovulation induction.

PMID- 12524055
TI  - Multiple births: how are we doing?

PMID- 12524056
TI  - Practice guidelines cannot be justified in the absence of sufficient evidence:
      inaction is far more appropriate than indefensible action.

PMID- 12524057
TI  - High-order multiple pregnancy: is it a matter of inaction or a consequence of
      practice patterns?

PMID- 12524058
TI  - Inappropriate use of cohort studies to formulate treatment guidelines.

PMID- 12524059
TI  - It has really been 15 years of inaction on high-order multiple pregnancies due to
      ovulation induction.

PMID- 12524060
TI  - Chromosomal abnormalities in embryos derived from testicular sperm extraction.
AB  - OBJECTIVE: To compare the rate of chromosome abnormalities in embryos obtained
      from karyotypically normal patients with nonobstructive azoospermia undergoing
      testicular sperm extraction (TESE) to those from patients undergoing
      intracytoplasmic sperm injection (ICSI) with ejaculated sperm. DESIGN:
      Retrospective analysis. SETTING: IVF centers. PATIENT(S): Male partners had
      either nonobstructive zoospermia or oligospermia. INTERVENTION(S):
      Preimplantation genetic diagnosis. Chromosome enumeration was performed by
      fluorescence in situ hybridization (FISH). Embryos classified as abnormal were
      reanalyzed to study mosaicism. MAIN OUTCOME MEASURE(S): Chromosome abnormalities
      in embryos. RESULT(S): Embryos from ICSI cycles with ejaculated sperm (group 1)
      were 41.8% normal, 26.2% aneuploid, and 26.5% mosaic. In contrast, the embryos
      from ICSI cycles with TESE for nonobstructive azoospermia (group 2) were 22%
      normal, 17% aneuploid, and 53% mosaic. The difference in mosaicism rate between
      the two groups of embryos was highly significant. CONCLUSION(S): The present
      study results indicate a high incidence of mosaicism in embryos derived from TESE
      in men with a severe deficit in spermatogenesis. Sperm derived from TESE for
      nonobstructive azoospermia may have a higher rate of compromised or immature
      centrosome structures leading to mosaicism in the embryo.

PMID- 12524061
TI  - Morphology and the sperm penetration assay.
AB  - OBJECTIVE: To assess the ability of Kruger morphology to predict the outcome of
      the sperm penetration assay (SPA). DESIGN: A retrospective review using
      univariate and multivariate analysis, t tests, and logistic regression was
      performed to examine the correlation between Kruger morphology and the optimized
      zona-free hamster egg sperm penetration assay (O-HESPA). SETTING: University
      hospital. PATIENT(S): One hundred fifteen private-practice patients who underwent
      semen analysis, including Kruger morphology and O-HESPA, as part of an
      infertility evaluation between 1997-2000 were retrospectively reviewed.
      INTERVENTION(S): Retrospective analysis of the sperm penetration assay. MAIN
      OUTCOME MEASURE(S): Univariate and multivariate analysis, Student's t test, and
      logistic regression were performed to analyze Kruger morphology, count, and
      viability and their relationship to SCI result. RESULT(S): Univariate analysis
      demonstrated a statistically significant correlation between SCI and sperm count,
      viability, and Kruger morphology. Multivariate analysis demonstrated
      statistically significant correlations between SCI and count and viability. There
      was no correlation between Kruger morphology and SCI. Logistic regression was
      performed on the SCI results, using count, Kruger morphology, and viability.
      Sperm count was found to be the only variable that was statistically significant
      with respect to SCI results. CONCLUSION: This study demonstrated that Kruger
      morphology assessment cannot be used to predict the results of SCI or replace it
      in the management of the infertile couple.

PMID- 12524062
TI  - Influence of individual sperm morphology on fertilization, embryo morphology, and
      pregnancy outcome of intracytoplasmic sperm injection.
AB  - OBJECTIVE: To evaluate the influence of morphology of individual spermatozoa on
      fertilization and pregnancy outcome. DESIGN: Retrospective analysis. SETTING: An
      IVF center in an institutional research environment. PATIENT(S): Fertilization
      and embryo quality according to individual sperm morphology were analyzed in 662
      consecutive ICSI cycles. Pregnancy outcome was evaluated for these cycles and an
      additional 1005 consecutive ICSI cycles. INTERVENTION(S): ICSI was performed
      using sperm cells of ejaculated, epididymal, or testicular origin. Observation
      through an inverted microscope was used to prospectively classify injected sperm
      cells as normal or morphologically abnormal. MAIN OUTCOME MEASURE(S): Oocyte
      fertilization, embryo morphology, and pregnancy outcome of unmixed embryo
      transfers. RESULT(S): Injection of morphologically abnormal spermatozoa
      (irrespective of origin) resulted in a lower fertilization rate (60.7%) than did
      injection of morphologically normal spermatozoa (71.7%). Embryo cleavage quality
      did not differ between groups. Higher pregnancy and implantation rates were
      obtained in patients with normal sperm morphology (36.7% and 18.7%, respectively)
      than in those with abnormal sperm morphology (20.2% and 9.6%). CONCLUSION(S):
      Individual sperm morphology assessed at the moment of ICSI correlated well with
      fertilization outcome but did not affect embryo development. The implantation
      rate was lower when only embryos resulting from injection of an abnormal
      spermatozoon were available.

PMID- 12524063
TI  - Relationship between zona pellucida-induced acrosome reaction, sperm morphology,
      sperm-zona pellucida binding, and in vitro fertilization.
AB  - OBJECTIVE: To evaluate the possible relationships between sperm morphology,
      acrosome responsiveness to solubilized human zona pellucida, and sperm-zona
      binding potential among [1] consecutive andrology referrals and [2] randomly
      selected in vitro fertilization (IVF) cases. DESIGN: Prospective analytical
      study. SETTING: Academic training hospital.Randomly selected couples consulting
      for infertility. INTERVENTION(S): Acrosome reaction response to solubilized human
      zona pellucida was recorded. MAIN OUTCOME MEASURE(S): We determined the
      difference in the percentage of sperm that acrosome reacted after exposure to
      solubilized zona pellucida and spontaneous acrosome reaction. The results were
      expressed as percentage zona induced acrosome reaction (ZIAR). RESULT(S): Data
      were analyzed using correlation coefficients (r) and receiver operator
      characteristics (ROC curve analyses). The ROC curve analyses indicated ZIAR to be
      a sensitive indicator for fertilization failure during IVF therapy, with
      sensitivity and specificity of 81% and 75%, respectively. For andrology
      referrals, a positive and statistically significant correlation existed between
      ZIAR data and sperm morphology (r = 0.65) and sperm-zona binding (r = 0.57).
      CONCLUSION(S): ZIAR results provide further information regarding dysfunctional
      sperm and can be used as an additional diagnostic test. Our results predicted
      fertilization failure during IVF treatment.

PMID- 12524064
TI  - Postoperative pain, complications, and satisfaction rates in patients who undergo
      surgical sperm retrieval.
AB  - OBJECTIVE: To determine patients' experiences with surgical sperm retrieval and
      its common complications. DESIGN: A questionnaire based survey using visual
      analogue scales (VAS) and closed questions to analyze complication, pain, and
      satisfaction rates. SETTING: Tertiary care university hospital. PATIENT(S): One
      hundred consecutive males undergoing surgical sperm retrieval by percutaneous
      epididymal sperm aspiration (PESA) or testicular sperm extraction (TESE).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We surveyed for pain perception
      complication rates and satisfaction scores. RESULT(S): Of the 85 patients who
      replied, 21 underwent retrieval for nonobstructive causes, 37 following failed
      reversal of vasectomy, and 27 for other obstructive causes. Retrieval was
      successful in 100% of obstructive causes and in 61% for nonobstructive
      azoospermia. Epididymal retrieval was successful in 23 patients, 30 patients
      underwent TESE after failed PESA, and 23 had TESE only. There were significant
      increases in pain perception scores and reported complications with TESE over
      PESA (31 vs. 16; and 21 out of 63 vs. 2 out of 22, respectively), but no
      difference in satisfaction rate. The cause of azoospermia did not affect pain
      perception or satisfaction in TESE. Complication rates were increased in larger
      testes (3 out of 22 vs. 24 out of 63). Unsuccessful sperm retrieval did not
      significantly affect patients' pain perception or satisfaction. Surgical sperm
      retrieval was rated as significantly less painful than both vasectomy and
      reversal (21% vs. 42% vs. 57%, respectively) and was associated with
      significantly fewer days absent from work (3.0 vs. 8.5). CONCLUSION(S): Surgical
      sperm retrieval by PESA or TESE is a safe procedure with only minor complications
      that is tolerated well by patients.

PMID- 12524065
TI  - Age is a better predictor of pregnancy potential than basal follicle-stimulating
      hormone levels in women undergoing in vitro fertilization.
AB  - OBJECTIVE: To analyze to what extent the parameters of ovarian functional reserve
      including female age and basal FSH levels will affect the results of ovarian
      hyperstimulation and IVF outcome. DESIGN: Retrospective cohort study. University
      hospital infertility center. PATIENT(S): One thousand forty-five women undergoing
      their first cycle of IVF with ovarian stimulation after pituitary
      desensitization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cycle
      parameters, cancellation rate, implantation rate, and pregnancy rate. RESULT(S):
      Both increasing age and basal FSH were associated significantly with reduced
      numbers of oocytes collected, oocytes fertilized, and embryos transferred. The
      combined use of age and basal FSH significantly improves the predictive power for
      these parameters. Increasing age, but not basal FSH, was associated significantly
      with reduced implantation rate and pregnancy rate. Logistic regression analysis
      revealed that age, but not basal FSH, was an independent predictor of pregnancy
      rate. Neither age nor basal FSH had significant association with fertilization
      rate, miscarriage rate, or ectopic pregnancy rate. CONCLUSION(S): Both basal FSH
      and age contributed to the prediction of the quantitative ovarian reserve as
      reflected by the number of oocytes collected. However, age is a better predictor
      of pregnancy potential for women undergoing IVF.

PMID- 12524066
TI  - Outcome for donors and recipients in two egg-sharing policies.
AB  - OBJECTIVE: To assess the effect of two different donation policies on results of
      egg-sharing. DESIGN: Retrospective analysis. SETTING: Tertiary referral center.
      PATIENT(S): One hundred five donor-recipient pairs participating in an egg
      sharing program between 1998 and 2001. INTERVENTION(S): Egg-sharing was performed
      according to policy A (retrieval of at least 12 oocytes, with more oocytes
      allocated to the donor) or policy B (retrieval of at least 8 oocytes, with equal
      distribution of oocytes between donors and recipients). MAIN OUTCOME MEASURE(S):
      Delivery rate and cycle cancellation rate. RESULT(S): Policy B resulted in a
      decreased cycle cancellation rate in the recipient group compared with policy A
      (9.7% vs. 29.7%, respectively; P<or=.01). No significant difference in delivery
      rate per fresh transfer was observed between policy A and policy B in donors
      (30.2% vs. 27.8%, respectively) or recipients (28.2% vs. 25.7%, respectively).
      CONCLUSION(S): Decreasing the number of oocytes required to perform egg sharing
      from 12 to 8 and dividing the oocytes equally between donors and recipients
      significantly reduces the cycle cancellation rate while it does not appear to
      affect adversely the probability of delivery.

PMID- 12524067
TI  - Disordered zona pellucida-induced acrosome reaction and failure of in vitro
      fertilization in patients with unexplained infertility.
AB  - OBJECTIVE: To determine the relationship between the zona pellucida (ZP)-induced
      acrosome reaction (AR) and fertilization rate and pregnancy rate in standard IVF
      and the frequency of disordered ZP-induced AR (DZPIAR) in patients with
      unexplained infertility. DESIGN: Prospective study. SETTING: Academic research
      and teaching tertiary hospital. PATIENTS: Patients with unexplained infertility
      with normal semen analysis. INTERVENTION: None. MAIN OUTCOME MEASURE: Semen
      analysis, the ZP-induced AR, and measurements of fertilization rate and pregnancy
      rate with in vitro fertilization (IVF) or intracytoplasmic sperm injection
      (ICSI). RESULT(S): A statistically significant correlation was found for the ZP
      induced AR and fertilization rate with standard IVF (n = 65). Patients with
      DZPIAR (ZP-induced AR of <or=16%) had an average fertilization rate of 23%, in
      contrast to patients with ZP-induced AR of >16%, who had an average fertilization
      rate of 61%. The sensitivity and specificity of DZPIAR for prediction of IVF
      rates <30% and >or=30% were 80% and 86%, respectively. Of 260 patients screened,
      the frequency of DZPIAR was 29%. Ten patients with DZPIAR had an average
      fertilization rate of 15% and no pregnancy with initial IVF cycles, and a
      fertilization rate of 61% (with three live-birth pregnancies) with subsequent
      ICSI cycles. Another 33 patients with DZPIAR were treated with ICSI alone, with
      an average fertilization rate of 71% and a live-birth pregnancy rate of 17% per
      embryo transfer. Sixteen of the patients had live-birth pregnancies (including
      one set of twins) after undergoing an average of 3.2 embryo transfers.
      CONCLUSION(S): Patients with DZPIAR have a low or zero fertilization rate with
      standard IVF but high fertilization and pregnancy rates with ICSI. Up to 29% of
      patients with unexplained infertility with normal semen analysis may have this
      condition, which should be diagnosed and treated with ICSI rather then standard
      IVF.

PMID- 12524068
TI  - Strategies and outcomes of the first 100 cycles of preimplantation genetic
      diagnosis at the Guy's and St. Thomas' Center.
AB  - OBJECTIVE: To establish strategies for the implementation of a successful
      preimplantation genetic diagnosis (PGD) service. DESIGN: Retrospective review of
      data from a single center. SETTING: A United Kingdom National Health Service
      hospital. PATIENT(S): Patients (60 couples) were referred for PGD from UK genetic
      centers. INTERVENTION(S): We followed the protocol of ovarian stimulation, oocyte
      retrieval, fertilization, single cell biopsy on day 3, and embryo transfer on day
      4. Pregnancies unaffected by the familial genetic condition. RESULT(S): A total
      of 60 couples was treated for 20 different conditions. Early cycles using
      nonsequential embryo culture media were less successful (13% pregnancy
      rate/embryo transfer) than later cycles using sequential media (33.5%). Ninety
      four percent of embryos (n = 473) had a single cell removed at biopsy. The
      overall pregnancy rate was 24% per cycle started, 29% per egg collection, 38% per
      transfer, and 40% per couple treated. In one cycle, an affected pregnancy
      followed PGD for spinal muscular atrophy (SMA). CONCLUSION(S): The use of
      sequential media and single cell biopsy results in a successful PGD program with
      encouraging pregnancy rates.

PMID- 12524069
TI  - Treatment of hyperandrogenic alopecia in women.
AB  - OBJECTIVE: To determine the effectiveness of various antiandrogens for the
      treatment of premenopausal women with hyperandrogenic alopecia. DESIGN:
      Randomized, unmasked trial of three treatments in 36 hyperandrogenic women with
      alopecia and observation, without treatment, in 12 other similar patients.
      SETTING: Endocrinologic outpatient practice in Italy. PARTICIPANT(S): A total of
      48 hyperandrogenic women with alopecia and 30 age- and weight-matched controls
      for the assessment of androgen levels. INTERVENTION(S): Randomization to
      cyproterone acetate (50 mg) with ethinyl estradiol (EE) in a reverse sequential
      regimen; flutamide (250 mg) or finasteride (5 mg) daily; all for 1 year. Twelve
      similar patients were observed without treatment for 1 year. MAIN OUTCOME
      MEASURE(S): Ludwig scores for hair thinning as well as patient and investigator
      assessments of treatment effectiveness. RESULT(S): Flutamide resulted in a
      reduction of 21% in Ludwig scores (2.3 +/- 0.2 to 1.8 +/- 0.1). The other
      treatment effects were not statistically significant. Patient and investigator
      assessments showed a similar trend. CONCLUSION(S): Flutamide at a dose of 250 mg
      daily induced a modest improvement in alopecia after 1 year, whereas cyproterone
      acetate and finasteride were not effective. Treatment for more than 1 year may be
      required for better results.

PMID- 12524070
TI  - Estrogen receptor thymine-adenine dinucleotide repeat polymorphism is associated
      with susceptibility to leiomyoma.
AB  - OBJECTIVE: To evaluate the association between leiomyomas and estrogen receptor
      gene polymorphism. DESIGN: Prospective study. SETTING: Department of gynecology
      and genetics. PATIENT(S): Women with (n = 159) or without leiomyomas (n = 131).
      MAIN OUTCOME MEASURE(S): Polymerase chain reaction was used to detect
      dinucleotide (thymine-adenine [TA]) repeat polymorphisms upstream of the estrogen
      receptor gene. Genotypes were classified as A through P according to the number
      of the TA repeats from 12 to 27. Distributions of TA repeat for estrogen receptor
      in both groups were compared. RESULT(S): Genotypes A to E were detected in 10.7%,
      18.9%, 15.7%, 16.4%, and 4.4%, respectively, of women with leiomyomas and 4.2%,
      9.5%, 20.6%, 19.1%, and 10.3% of women without leiomyomas. Women with genotypes A
      and B (12 or 13 TA repeats) have a higher risk for leiomyomas, and those with
      genotype E (16 TA repeats) have a lower risk. CONCLUSION(S): Estrogen receptor
      gene polymorphism probably contributes to the pathogenesis of leiomyoma and may
      predict the susceptibility to leiomyoma. The 12 and 13 TA repeats are associated
      with a higher risk of leiomyoma.

PMID- 12524071
TI  - Comparison of ultrasonographic and Doppler mapping of the intervillous
      circulation in normal and abnormal early pregnancies.
AB  - OBJECTIVE: To assess the value of ultrasonography and Doppler imaging in
      characterizing the intervillous circulation in normal and abnormal early
      pregnancy. DESIGN: Cross-sectional study. SETTING: Tertiary care academic
      hospital. PATIENT(S): Eighty-five normal pregnancies and 125 missed miscarriages
      at 7 to 13 weeks of gestation. INTERVENTION(S): Grey-scale ultrasonography was
      used to evaluate the placental anatomy and detect moving echoes inside the
      intervillous space, and color power Doppler imaging was used to detect continuous
      venous-like flow in the placental tissue. MAIN OUTCOME MEASURE(S): Degree of
      agreement between two investigators for use of grey-scale imaging, comparison of
      detection of moving echoes in normal and abnormal pregnancies, and comparison of
      detection of intervillous circulation with grey-scale and color Doppler imaging
      in abnormal pregnancies. RESULT(S): The overall degree of agreement between the
      two investigators was good. A significantly different distribution of blood flow
      was found between normal and abnormal pregnancies at 7 to 9 weeks and 10 to 11
      weeks but not at 12 to 13 weeks. Intervillous moving echoes were detected by grey
      scale imaging significantly more frequently than an intervillous blood flow was
      detected with color Doppler imaging. CONCLUSION(S): In early pregnancy failure,
      there is a premature and diffuse onset of intervillous blood flow that can be
      detected by grey-scale imaging. This abnormal blood flow pattern may increase the
      oxidative stress on the early placental tissue and subsequently impair placental
      development.

PMID- 12524072
TI  - Selective uterine artery embolization in the management of uterine myomas.
AB  - OBJECTIVE: To evaluate the effectiveness of uterine artery embolization in women
      with uterine myomas in terms of the clinical results for the relief of related
      symptoms. DESIGN: A pilot study on 26 women affected by uterine single myoma.
      SETTING: Tertiary level care in an university hospital. PATIENT(S): Twenty-six
      patients, aged 32 to 54 years, suffering of menorrhagia, pelvic pain, and
      abdominal mass for single myoma, intramural localization. INTERVENTION(S):
      Selective uterine artery embolization performed under peridural anesthesia. MAIN
      OUTCOME MEASURE(S): We measured the x-ray dose to which patients were exposed.
      Color power Doppler ultrasound examinations were performed during the follow-up
      evaluations at 1 to 6 months and 1 year after the procedure. RESULT(S): Uterine
      artery embolization was successfully performed in 100% of cases. The mean
      fluoroscopy time was of 20 minutes during the procedure. The mean dose of x-ray
      absorbed by the ovary was estimated at 18.7 cGy and the mean dose of x-ray
      absorbed by the skin was 126.7 cGy. A reduction of myoma volume of 55% was found
      at 6 months' ultrasound examination and 75% at the 1-year examination.
      CONCLUSION(S): Patients are well satisfied and have short recovery times with
      this procedure. Uterine artery embolization may be a valid alternative to
      traditional surgery.

PMID- 12524073
TI  - The Ontario Uterine Fibroid Embolization Trial. Part 1. Baseline patient
      characteristics, fibroid burden, and impact on life.
AB  - OBJECTIVE: To determine baseline characteristics of women undergoing uterine
      artery embolization (UAE) for symptomatic fibroids. DESIGN: Multicenter,
      prospective, single-arm clinical treatment trial. SETTING: Eight Ontario
      university and community hospitals. PATIENT(S): Five hundred fifty-five women
      undergoing UAE for fibroids. INTERVENTION(S): Baseline questionnaires completed
      before UAE. MAIN OUTCOME MEASURE(S): Questionnaires were analyzed for
      demographic, medical, and gynecologic histories. Fibroid symptoms, impact of
      symptoms, previous consultations, and treatments were also analyzed. RESULT(S):
      The Ontario cohort (66% white, 23% black, 11% other races) had an average age of
      43. Thirty-one percent were under age 40. Most women were university educated
      (68%) and working outside the home (85%). Women reported heavy menstrual bleeding
      (80%), urinary urgency/frequency (73%), pain during intercourse (41%), and work
      absences (40%). They experienced fibroid-related symptoms for an average of 5
      years and consulted with on average of three gynecologists before UAE. High
      fibroid life-impact scores were reported by 58%. Black women were significantly
      younger (40.7 vs. 44.0 years), more likely to experience symptoms longer (7 vs. 5
      years), and more likely to undergo myomectomy before UAE (24% vs. 9%) than white
      women. CONCLUSION(S): Our study illustrates that large numbers of women with
      highly symptomatic fibroid disease are averse to surgery despite their burden of
      suffering and are actively seeking alternatives to hysterectomy.

PMID- 12524074
TI  - The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction
      and symptom relief after uterine artery embolization for fibroids.
AB  - OBJECTIVE: To evaluate fibroid uterine volume reduction, symptom relief, and
      patient satisfaction with uterine artery embolization (UAE) for symptomatic
      fibroids. DESIGN: Multicenter, prospective, single-arm clinical treatment trial.
      SETTING: Eight Ontario university and community hospitals. Five hundred thirty
      eight patients undergoing bilateral UAE. INTERVENTION(S): Bilateral UAE performed
      with polyvinyl alcohol particles sized 355-500 microm. MAIN OUTCOME MEASURE(S):
      Three-month follow-up evaluations including fibroid uterine volume reductions,
      patient reported symptom improvement (7-point scale), symptom life-impact (10
      point scale) reduction, and treatment satisfaction (6-point scale). RESULT(S):
      Median uterine and dominant fibroid volume reductions were 35% and 42%,
      respectively. Significant improvements were reported for menorrhagia (83%),
      dysmenorrhea (77%), and urinary frequency/urgency (86%). Mean menstrual duration
      was significantly reduced after UAE (7.6 to 5.4 days). Improvements in
      menorrhagia were unrelated to pre-UAE uterine size or post-UAE uterine volume
      reduction. Amenorrhea occurring after the procedure was highly age dependent,
      ranging from 3% (1%-7%) in women under age 40 to 41% (26%-58%) in women age 50 or
      older. Median fibroid life-impact scores were significantly reduced after UAE
      (8.0 to 3.0). The majority (91%) expressed satisfaction with UAE treatment.
      CONCLUSION(S): UAE reduced fibroid uterine volume and provided significant relief
      of menorrhagia that was unrelated to initial fibroid uterine size or volume
      reduction. Patient satisfaction with short-term UAE treatment outcomes was high.

PMID- 12524075
TI  - Serious complications of uterine artery embolization for conservative treatment
      of fibroids.
AB  - OBJECTIVE: Document major complications following treatment of fibroids by
      uterine artery embolization (UAE). DESIGN: Two case reports. SETTING: University
      medical center. PATIENTS: Two women with symptomatic fibroid uteri.
      INTERVENTION(S): Selective bilateral uterine artery embolization. MAIN OUTCOME
      MEASURE(S): Complications attributable to UAE. RESULT(S): Two patients
      experienced significant morbidity requiring hysterectomy due to infection and/or
      partial bowel obstruction resulting from UAE. CONCLUSION(S): Reports of the
      management of symptoms related to fibroids with UAE infrequently include adverse
      outcomes and/or complications. The two cases we managed reinforce that UAE is not
      free of the risk of life-threatening complications that require emergency
      hysterectomy. Increasing surveillance for complications may help define the
      selection criteria that decrease the risks of UAE.

PMID- 12524076
TI  - Permanent amenorrhea associated with endometrial atrophy after uterine artery
      embolization for symptomatic uterine fibroids.
AB  - OBJECTIVE: To report a case of permanent amenorrhea associated with endometrial
      atrophy after uterine artery embolization for symptomatic uterine fibroids.
      DESIGN: Case report. SETTING: Gynecologic clinic of a university hospital.
      PATIENT(S): A 44-year-old woman with menorrhagia and anemia caused by multiple
      fibroids. INTERVENTION(S): Transcatheter bilateral uterine artery embolization
      with polyvinyl alcohol particles, with hormonal, sonographic, and hysteroscopic
      follow-up procedures. MAIN OUTCOME MEASURE(S): Serum follicle-stimulating hormone
      (FSH) and estradiol levels were measured, and sonographic appearance of the
      ovaries and the endometrium at baseline and 1, 3, 6, and 12 months after
      treatment were recorded. Hysteroscopy was performed with endometrial biopsy at
      baseline and 6 months after embolization. RESULT(S): The patient remained
      amenorrheic from the procedure. Serial posttreatment measurements of FSH and
      estradiol levels and repeated ovarian imaging showed no change in ovarian
      function as compared with baseline. A reduction in endometrial thickness (<or=5
      mm), as compared with the endometrial thickness measured at baseline (7.2 mm),
      was sonographically documented 1, 3, 6, and 12 months after treatment.
      Postprocedure hysteroscopy showed an atrophic endometrium, and endometrial biopsy
      confirmed endometrial atrophy. CONCLUSION(S): Permanent amenorrhea associated
      with endometrial atrophy may occur following uterine artery embolization for
      fibroids and, to the best of our knowledge, this is the first time this
      complication has been reported. Patients should be appropriately counseled about
      the risk of reduced fertility after embolization.

PMID- 12524078
TI  - Role of plasminogen activators during healing after uterine serosal lesioning in
      the rat.
AB  - OBJECTIVE: Study the expression pattern of tissue-type (t-PA) and urokinase-type
      (u-PA) plasminogen activators during uterine serosal healing after lesioning in a
      rat model. DESIGN: Descriptive study with an adhesion model using reverse
      transcriptase-polymerase chain reaction (PCR) and immuncytochemical techniques.
      SETTING: Academic medical center. PATIENT(S): None. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Expression profiles of t-PA and u-PA were examined in the
      uteroperitoneal adhesion tissues of rat from the time of injury until day 7 after
      surgery using relative abundance reverse transcriptase-PCR and immunocytochemical
      techniques. RESULT(S): The t-PA transcript levels dropped in uteroperitoneal
      tissues by 6 hours after surgery and remained low until day 5. Thereafter, a
      rapid up-regulation of this transcript was observed at day 7. In contrast, the u
      PA transcript levels demonstrated a biphasic profile during the progression of
      adhesion development with peaks at 2 and 5 days after surgery. Immunocytochemical
      staining demonstrated expression of these plasminogen activators in the newly
      formed blood vessels. CONCLUSION(S): Altered levels of t-PA and u-PA transcripts
      and its expression in newly formed blood vessels during healing and adhesion
      development indicate involvement of these plasminogen activators in serosal
      healing and adhesion development.

PMID- 12524079
TI  - Secretion of granulocyte chemotactic protein-2 by cultured human endometrial
      stromal cells.
AB  - OBJECTIVE: To evaluate the expression of granulocyte chemotactic protein-2 (GCP
      2) in human endometrial stromal cells. DESIGN: The effects of interleukin (IL)
      1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha, TNF-beta, interferon (IFN)
      gamma, and lipopolysaccharide (LPS) on the production of GCP-2 by endometrial
      stromal cells were investigated. SETTING: Research laboratory at a medical
      university. PATIENT(S): Eight endometrial specimens in the late proliferative
      phase were used. INTERVENTION(S): Endometrial stromal cells were incubated for 24
      hours with IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, IFN-gamma, and LPS.The
      concentration of GCP-2 in the culture media was measured using an enzyme-linked
      immunosorbent assay (ELISA). RESULT(S): A small amount of GCP-2 was detected in
      the culture media of unstimulated endometrial stromal cells. The production of
      GCP-2 by endometrial stromal cells was stimulated with IL-1alpha, IL-1beta, TNF
      alpha, TNF-beta, and LPS in a dose-dependent manner. Interferon-gamma did not
      affect GCP-2 production by these cells. CONCLUSION(S): These results suggest that
      GCP-2 is an additional ELR(+)-CXC chemokine expressed in endometrial stromal
      cells. The modulation of GCP-2 concentrations in the local environment may
      contribute to the normal and pathological processes of human reproduction by
      regulating the neutrophil trafficking in the endometrium.

PMID- 12524080
TI  - Interleukin-8 gene and protein expression are up-regulated by interleukin-1beta
      in normal human ovarian cells and a granulosa tumor cell line.
AB  - OBJECTIVE: To evaluate the expression, regulation, and role of interleukin (IL)-8
      in human ovary. DESIGN: Prospective study. SETTING: University hospital.
      PATIENT(S): Sixteen premenopausal women. INTERVENTION: Follicular fluid and
      granulosa lutein cells (GLCs) were collected during IVF cycles. Ovarian stromal
      and theca cells were obtained from women underwent surgery. KGN cells, the human
      granulosa cell tumor cell line, were also used. MAIN OUTCOME MEASURES: The levels
      of IL-8 and IL-1beta in follicular fluid and IL-8 protein production were
      determined using ELISA. Interleukin-8 and IL-8 receptor gene expression in
      ovarian cells and the effect of IL-8 on the proliferation of stromal cells were
      determined. The expression of pIkappaB was evaluated by Western blot, and the
      effect of NF-kappaB inhibitor APDC was examined by Northern blot analysis and
      ELISA in KGN cells. The levels of IL-8 and IL-1beta in follicular fluid; each
      concentration and the volume showed a positive correlation. Reverse transcription
      polymerase chain reaction showed the presence of IL-8 mRNA in all ovarian cells.
      In contrast, IL-8 receptor mRNA was only detected in stromal cells. The
      expression of IL-8 in GLCs and KGN cells was increased by addition of IL-1beta
      and TNFalpha. Interleukin-8 increased the proliferation of ovarian stromal cells.
      The expression of pIkappaB in KGN cells was induced by IL-1beta, and the effects
      were reduced by APDC. CONCLUSION(S): Interleukin 8 induced by IL-1beta via
      activation of NF-kappaB in granulosa cells may have a role in the periovulatory
      period of follicular maturation.

PMID- 12524081
TI  - Effect of glucose on the expression of type I collagen and transforming growth
      factor-beta1 in cultured human peritoneal fibroblasts.
AB  - OBJECTIVE: To determine the effect of high glucose levels on the expression of
      type I collagen, and whether this effect is regulated by transforming growth
      factor (TGF)-beta1 in human peritoneal fibroblasts in culture. DESIGN:
      Prospective experimental study. SETTING: University medical center. PATIENT(S):
      Primary cultures of fibroblasts established from peritoneal tissues of five
      patients. High glucose treatment of the primary cultured fibroblasts. MAIN
      OUTCOME MEASURE(S): Primary cultures of human peritoneal fibroblasts were
      incubated with varying amounts of glucose (1-5 g/L) for 24 hours. Total RNA was
      extracted from human peritoneal fibroblasts and converted to cDNA by reverse
      transcriptase. Multiplex reverse transcriptase/polymerase chain reaction (PCR)
      simultaneously co-amplifying beta-actin with TGF-beta1 or type I collagen mRNAs
      was used to quantitate type I collagen and TGF-beta1 mRNA levels in response to
      increasing glucose concentrations with and without TGF-beta1 antibody treatment.
      RESULT(S): There was a significant increase in the mRNA for type I collagen and
      TGF-beta1 in response to increasing glucose concentrations in a dose response
      dependent manner. The TGF-beta1 antibody treatment resulted in an 83% and 68%
      decrease in type I collagen and TGF-beta1 mRNA levels, respectively.
      CONCLUSION(S): Increasing glucose concentrations stimulated type I collagen
      expression in human peritoneal fibroblasts in culture. A potential mediator for
      this effect is TGF-beta1. These results have implications not only for
      individuals with diabetes mellitus who may be predisposed to greater
      postoperative adhesion development, but also for individuals with surgical stress
      responses after surgery.

PMID- 12524082
TI  - Modulation of the expression of tissue plasminogen activator and its inhibitor by
      hypoxia in human peritoneal and adhesion fibroblasts.
AB  - OBJECTIVE: To determine whether normal peritoneal and adhesion fibroblasts
      express tissue plasminogen activator (tPA) and plasminogen activator inhibitor
      (PAI-I) and whether their expression is regulated by oxygen. DESIGN: Prospective
      experimental study. SETTING: University medical center. PATIENT(S): Cultures of
      human fibroblasts established from peritoneal and adhesion tissues. Hypoxia
      treatment of the primary cultured fibroblasts. MAIN OUTCOME MEASURE(S): We have
      used the multiplex reverse transcription polymerase chain reaction (RT-PCR)
      technique to determine the effect of hypoxia on the expression of tPA and PAI-I
      in normal peritoneal (NPF) and adhesion (ADF) fibroblasts. Cultures of NPF and
      ADF were exposed to hypoxia (2% O(2)) for 24 hours. RNA was extracted from cells
      and subjected to multiplex RT-PCR to quantitate relative changes in mRNA levels
      of tPA and PAI-I in response to hypoxia treatment. RESULT(S): Basal tPA mRNA
      levels are present in both NPF and ADF and were 45% higher in NPF than ADF.
      Hypoxia decreased tPA in both NPF and ADF by 74% and 95%, respectively. Basal PAI
      I mRNA levels were 64% higher in ADF than in NPF. Hypoxia increased PAI-I mRNA
      levels by 67% and 53% in NPF and ADF, respectively. CONCLUSION(S): Plasminogen
      activator activity (PAA) of the peritoneum does not solely reside in the
      mesothelial cells, as previously identified, but also exists within fibroblasts,
      thus providing the potential to resolve postoperative fibrinous collections even
      at sites at which the mesothelial cells have been injured, removed, or destroyed.
      Furthermore, PAA in fibroblasts is regulated by oxygen; creation of a hypoxic
      state markedly attenuates PAA, thereby leading to adhesion development.

PMID- 12524083
TI  - Glutathione and glutathione S-transferases A1-1 and P1-1 in seminal plasma may
      play a role in protecting against oxidative damage to spermatozoa.
AB  - OBJECTIVE: To study the levels of glutathione, glutathione S-transferase A1-1,
      and glutathione S-transferase P1-1 in seminal fluid of fertile and subfertile
      men. DESIGN: Retrospective case-control study. SETTING: Departments of
      gastroenterology, obstetrics and gynecology, and epidemiology and biostatistics
      in a university medical center. PATIENT(S): Twenty-five subfertile men visiting
      the fertility clinic and 25 fertile men from midwife practices were recruited.
      INTERVENTION(S): Collection of semen of subfertile and fertile men. MAIN OUTCOME
      MEASURE(S): Plasma levels of glutathione and glutathione S-transferases A1-1 and
      P1-1 in relation to seminal characteristics. RESULT(S): Glutathione, glutathione
      S-transferase A1-1, as well as glutathione S-transferase P1-1 were found in
      considerable amounts in seminal fluid of subfertile and fertile men. No
      differences between groups were found for glutathione S-transferases A1-1 and P1
      1. Also, no associations with sperm count, motility, or morphology could be
      detected. Fertile men had significantly higher glutathione levels as compared
      with the case of subfertile men. Associations of glutathione with sperm motility
      quality (r(s) = 0.321) and abnormal sperm morphology (r(s) = -0.496) were found.
      CONCLUSION(S): The presence of glutathione S-transferases A1-1 and P1-1 in
      seminal fluid suggests a role in the protection against (oxidative) damage of
      spermatozoa, whereas glutathione may play a role in male fertility.

PMID- 12524084
TI  - Immunoexpression of hepatocyte growth factor and c-Met receptor in the eutopic
      endometrium predicts the activity of ectopic endometrium.
AB  - OBJECTIVE: To investigate the mitogenic and angiogenic activity of the eutopic
      and ectopic endometrium throughout the menstrual cycle and to examine whether the
      activity of the eutopic endometrium is useful to predict greater activity of the
      ectopic endometrium. DESIGN: Controlled clinicopathologic study using intact
      tissue. SETTING: Nagasaki University School of Medicine, Nagasaki, Japan.
      PATIENT(S): Fifteen infertile women with pelvic endometriosis and 10 women
      without endometriosis undergoing laparoscopy. INTERVENTION(S): Biopsies from the
      ectopic endometrium and the corresponding eutopic endometrium were collected.
      Immunohistochemical staining was performed using respective antibodies, and a
      computer analyzed modified quantitative-histogram (Q-H) score was used to
      quantify immunostaining. MAIN OUTCOME MEASURE(S): The immunoreactions of
      hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth
      factor (VEGF), proliferating cell nuclear antigen (PCNA), and von Willebrand
      factor (VWF) in eutopic and ectopic endometrium were examined, and their relation
      with different revised American Society for Reproductive Medicine (r-ASRM) stages
      and the morphology of endometriosis was evaluated. RESULT(S): The
      immunoexpressions of HGF and c-Met were significantly higher in the eutopic
      endometrium of patients with endometriosis than in that of controls. The Q-H
      scores of HGF, c-Met, VEGF, PCNA, and microvessel density (MVD) were markedly
      higher in red peritoneal lesions when compared with other lesions. The Q-H scores
      did not reveal r-ASRM stage-dependent variation in any of these markers. We
      observed a significant correlation between the immunoexpressions of HGF, c-Met,
      and PCNA or microvessel counts. When we combined the Q-H scores of the glandular
      epithelium and stroma, we found that increased activity of the eutopic
      endometrium as measured by the immunoreaction of HGF, c-Met, VEGF, PCNA, and MVD
      was similar to highly active red lesions and was significantly higher than that
      of controls and other lesions. CONCLUSION(S): Immunoexpression of HGF and c-Met
      in the eutopic endometrium of patients with pelvic endometrioisis is possibly
      useful to predict greater activity of the ectopic endometrium.

PMID- 12524085
TI  - Prolactin gene expression in human ovarian follicular cells.
AB  - OBJECTIVE: To investigate prolactin gene expression in human ovarian follicular
      cells. DESIGN: RNA was isolated from follicular cells obtained at the time of
      transvaginal oocyte retrieval from patients after controlled ovarian
      hyperstimulation. The RNA was subjected to reverse transcription and polymerase
      chain reaction (RT-PCR) using prolactin-specific primers. The RT-PCR products
      were analyzed by gel electrophoresis, followed by Southern blot analysis using
      prolactin-specific probes. SETTING: Department of gynecology and obstetrics
      research laboratory. PATIENT(S): Women undergoing controlled ovarian
      hyperstimulation followed by transvaginal oocyte retrieval. INTERVENTION(S):
      Controlled ovarian hyperstimulation followed by transvaginal oocyte retrieval.
      Expression of prolactin mRNA by follicular cells. RESULT(S): The presence of
      prolactin-specific cDNA amplified by RT-PCR from RNA isolated from human
      follicular cells was confirmed by Southern blot analysis. CONCLUSION(S): Human
      ovarian follicular cells are an extrapituitary site of prolactin gene expression.

PMID- 12524086
TI  - Usefulness and prognostic value of transvaginal hydrolaparoscopy in infertile
      women.
AB  - OBJECTIVE: To evaluate the usefulness and prognostic value of transvaginal
      hydrolaparoscopy (THL) in infertile women. DESIGN: Retrospective study. SETTING:
      Jichi Medical School Hospital, Tochigi, Japan. PATIENT(S): Thirty-six patients
      who were followed up for 6 months or longer after THL was performed.
      INTERVENTION(S): Transvaginal hydrolaparoscopy findings in comparison with
      hysterosalpingography (HSG). MAIN OUTCOME MEASURES: Transvaginal hydrolaparoscopy
      findings, HSG findings, treatment strategy, and prognosis. RESULT(S): Twenty of
      36 patients (55.5%) became pregnant, including 7 by coitus, 7 by artificial
      insemination with the husband's semen, and 6 by assisted reproductive technology
      (ART). In 11 of these pregnant patients, information obtained during THL differed
      from findings on HSG. CONCLUSION(S): Transvaginal hydrolaparoscopy is useful in
      selecting a future treatment strategy.

PMID- 12524087
TI  - Three-dimensional ultrasonographic ovarian measurements and in vitro
      fertilization outcome are related to age.
AB  - OBJECTIVE: To evaluate whether the number of ovarian antral follicles, ovarian
      volume, and ovarian stromal blood flow change with age and to prospectively
      analyze whether three-dimensional ultrasonographic measurements predict ovarian
      response and IVF outcome. DESIGN: Prospective analysis. SETTING: Assisted
      reproductive unit. PATIENT(S): Fifty-six consecutive women 22 to 43 years of age
      with normal basal serum FSH concentrations who were undergoing their first IVF
      cycle. MAIN OUTCOME MEASURE(S): Number of ovarian antral follicles, ovarian
      volume, and ovarian stromal flow index were determined by three-dimensional and
      power Doppler ultrasonography. Pretreatment measurements were compared with
      number of recovered oocytes, fertilization rates, and pregnancy rates. RESULT(S):
      As patient age increased, significant trends in ovarian volume, number of
      follicles, and stromal vascularity decreased. Three-dimensional ovarian
      measurements and fertilization rates differed significantly among age groups. For
      each age group, a higher number of antral follicles, greater ovarian volume, and
      favorable ovarian stromal vascularity was associated with higher number of
      retrieved oocytes and increased pregnancy rates. CONCLUSION(S): Increasing
      patient age is associated with poor ovarian response, as represented by smaller
      ovarian volume, lower antral follicle count, and poor stromal vascularity. Three
      dimensional power Doppler ultrasonography can help to individualize IVF in
      patients regardless of age.

PMID- 12524088
TI  - Use of the PROACT System for reduction of postsurgical peritoneal adhesions.
AB  - OBJECTIVE: To assess the efficacy and safety of a new surgical device designed to
      prevent adhesions. DESIGN: Prospective, controlled two-phase porcine study.
      SETTING: Good Laboratory Practice-certified animal facility. ANIMAL(S): Phase I:
      10 pigs underwent peritoneal treatment with the PROACT System (NTERO Surgical,
      Inc., Palo Alto, California) at the time of the laparotomy incision, and four had
      the incision made without treatment. Phase II: 22 animals were randomized to
      treatment or control groups. INTERVENTION(S): Animals in both groups underwent
      laparotomy incision and small bowel resection. The treatment group received
      treatment to the peritoneum before the peritoneal incision was made. Necropsy and
      adhesion evaluation were conducted by a blinded reviewer 7-13 days after the
      initial surgery. MAIN OUTCOME MEASURE(S): Presence or absence of adhesions.
      RESULT(S): Phase I: no treated animal developed adhesions to the incision site;
      three of four control animals developed adhesions to the incision site. Phase II:
      4 of 10 control animals and no treated animals developed midline abdominal wall
      adhesions. Distal adhesions tended to also be reduced in treated animals. No side
      effects or increased risks were noted. CONCLUSION(S): The PROACT System appears
      to be safe and efficacious in reducing adhesions to the laparotomy incision line
      in the porcine model.

PMID- 12524089
TI  - Use of clomiphene citrate to reverse premature andropause secondary to steroid
      abuse.
AB  - OBJECTIVE: To report a case of symptomatic hypogonadism induced by the abuse of
      multiple steroid preparations that was subsequently reversed by clomiphene.
      DESIGN: Case report. SETTING: University-affiliated andrology practice within
      family practice clinic. PATIENT(S): A 30-year-old male. INTERVENTION(S):
      Clomiphene citrate, 100-mg challenge for 5 days, followed by treatment at same
      dose for 2 months. MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen decline
      in aging male questionnaire, total T, FSH, LH. RESULT(S): Reversal of symptoms,
      normalization of T levels with LH surge, restoration of pituitary-gonadal axis.
      CONCLUSION(S): Clomiphene citrate is used typically in helping to restore
      fertility in females. This represents the first case report of the successful use
      of clomiphene to restore T levels and the pituitary-gonadal axis in a male
      patient. The axis was previously shut off with multiple anabolic steroid abuse.

PMID- 12524090
TI  - Fertility in a female with mosaic trisomy 8.
AB  - OBJECTIVE: To describe the first term pregnancy in a patient with the
      characteristic features of trisomy 8 mosaicism. DESIGN: Case report. SETTING:
      University department. PATIENT(S): The 23-year-old proband had a history of cleft
      palate, mixed bilateral hearing loss, short stature, and developmental delay. She
      had dysmorphic craniofacial features, mild musculoskeletal abnormalities, and
      abnormal skin pigmentation. Her karyotype was mos47,XX,+8[17]/46,XX[83].
      INTERVENTION(S): Cytogenetic analysis and genetics evaluation of the proband and
      her child. MAIN OUTCOME MEASURE(S): The first successful pregnancy in a
      phenotypically abnormal trisomy 8 patient. RESULT(S): The pregnancy was largely
      uncomplicated except for an abnormal triple screen, with subsequent normal
      amniocentesis, and a fetal ultrasound revealing a clubfoot anomaly. Cytogenetic
      analysis of the child showed a 46,XX karyotype. CONCLUSION(S): Our review
      indicates that reproduction in females with mosaic trisomy 8 is possible, albeit
      uncommon. Until additional cases are reported and any specific risks identified,
      prenatal diagnosis of any pregnancies in mosaic trisomy 8 patients would seem
      prudent. In addition, this and previous cases illustrate the need to effectively
      counsel families of mosaic trisomy 8 children about the possibility of
      reproduction.

PMID- 12524091
TI  - Severe ovarian dysgenesis and enlarged dysplastic kidneys in two siblings with
      normal karyotypes.
AB  - OBJECTIVE: To report a rare case of two normally karyotyped 46,XX siblings with
      severe ovarian dysgenesis and enlarged dysplastic kidneys. DESIGN: Case report.
      Rabin Medical Center, a major tertiary university-affiliated care and referral
      facility. PATIENT(S): A healthy 30-31-year-old woman underwent termination of two
      pregnancies at 22 and 23 gestational weeks because of ultrasonographic
      observations of enlarged kidneys in both fetuses. INTERVENTION(S): Prostaglandin
      induced pregnancy terminations with feticide. MAIN OUTCOME MEASURE(S): Light
      microscopy observations. RESULT(S): Both siblings had a 46,XX karyotype, and the
      maternal alpha-fetoprotein level was within normal limits. In the first, no
      ovaries were identified, and in the second, bilateral streak ovaries devoid of
      ova were noted. In both cases, pathological examinations identified large
      dysplastic kidneys, with dysplastic changes in certain medullary areas. Apart
      from the kidneys and ovaries, all other organs were normal. CONCLUSION(S): To the
      best of our knowledge, this is the first report of two normally karyotyped 46,XX
      siblings with severe ovarian dysgenesis and renal abnormalities but without any
      other malformations.

PMID- 12524092
TI  - Sperm chromosomal abnormalities are linked to sperm morphologic deformities.
AB  - OBJECTIVE: To describe the association between specific sperm morphologic
      abnormalities and sperm chromosomal abnormalities on multicolor interphase
      fluorescence in situ hybridization (FISH). DESIGN: Case report. Reproductive
      medicine unit in a tertiary referral center. PATIENT(S): Three infertile men with
      severe oligoasthenospermia and total teratozoospermia who were referred for IVF
      treatment. MAIN OUTCOME MEASURE(S): Incidence of spermatozoal chromosomal
      aneuploidy for chromosome 18 and the sex chromosomes by using FISH. RESULT(S):
      Morphologic assessment of sperm revealed a high incidence of double heads,
      multinucleated sperm heads, and multiple tails. Hormone profiles and karyotyping
      of peripheral lymphocytes were normal in the three men. The proportion of sperm
      with disomy, trisomy and tetrasomy for chromosome 18, and the sex chromosomes in
      each patient was 100%, 76%, and 82.5%, respectively. CONCLUSION(S): Specific
      morphologic abnormalities of sperm may be associated with higher incidence of
      chromosomal abnormalities. Resolving infertility by offering patients in vitro
      fertilization/intracytoplasmic sperm injection must be approached with caution
      because of the significant risk for embryonic aneuploidy and chromosomal
      abnormalities in any subsequent offspring.

PMID- 12524093
TI  - Inability of mature oocytes to create functional haploid genomes from somatic
      cell nuclei.

PMID- 12524094
TI  - Association between the D19S884 marker at the insulin receptor gene locus and
      polycystic ovary syndrome.

PMID- 12524095
TI  - Topical progesterone cream has an antiproliferative effect on estrogen-stimulated
      endometrium.

PMID- 12524096
TI  - Growth effects of raloxifene, estradiol, medroxy-progesterone acetate, and
      progesterone on human endometrial adenocarcinoma cells.

PMID- 12524097
TI  - Pregnancy in rabbits actively immunized against bovine pregnancy-associated
      glycoprotein 1.

PMID- 12524098
TI  - Blastocyst transfer decreases multiple pregnancy rates in in vitro fertilization
      cycles: a randomized controlled trial.

PMID- 12524099
TI  - A pilot study of the efficacy of intracytoplasmic sperm injection in a natural
      cycle.

PMID- 12524100
TI  - Functional status of the Sertoli cell in azoospermic men.

PMID- 12524102
TI  - Effect of FSH priming on response to hCG in subjects with follicle stimulating
      hormone receptor (FSHR) mutations.

PMID- 12524104
TI  - Decision-making when science is ambiguous.

PMID- 12524106
TI  - Decision-making when science is ambiguous.

PMID- 12524111
TI  - Absolute line intensities determination in the nu7 band of C2H4.
AB  - Absolute intensities have been measured for 26 lines of C2H4 in the nu7
      fundamental transition, using a tunable diode-laser spectrometer. These lines
      with 3< or = J"< or = 21, 2< or = Ka< or = 4, 2< or = Kc< or = 20 are located in
      the spectral range 920-980 cm(-1). The intensities have been measured by using
      two methods: the equivalent width method (EWM) and the line profile fit method
      (FPM). For the last one, three models have been tested: Voigt, Rautian and
      Galatry profiles.

PMID- 12524110
TI  - Pressure broadening study of carbon disulfide for atmospheric detection.
AB  - Preliminary results for collisional broadening are reported for two lines P(8)
      and R(32) of the nu3-nu1 band of CS2 in mixture with O2 and air. These values and
      previous results for CS2-N2 enable us to compare the broadening coefficients
      directly obtained for CS2-air with those derived from CS2-N2 and CS2-O2.

PMID- 12524112
TI  - Cyanogen chloride: self-broadening and intensities in the region of 13 microm.
AB  - This work presents a synthesis of our results concerning line intensities and
      self-broadening coefficients for ClCN in the diad (nu1, 2nu 2 0). Absolute band
      strengths have been determined. The influence of the perturbation in these band
      strengths due to a Fermi resonance between the 10(0)0 and 02(0)0 levels has been
      analyzed.

PMID- 12524113
TI  - The Cologne Carbon Cluster experiment: ro-vibrational spectroscopy on C8 and
      other small carbon clusters.
AB  - We report on our ongoing efforts in obtaining the IR-spectra of the linear carbon
      cluster molecules Cn with n=8-13. So far C8, C9, C10, and C13 have been recorded
      at Cologne. With the exception of C8 all assignments have been secured. For C8 a
      tentative assignment could be derived with the bandcenter of the sigmau
      antisymmetric stretching mode located at nu0=2067.9779 cm(-1) and a preliminary
      rotational constant in the vibrational ground state of B"=0.02068 cm(-1). The
      measured signal to noise ratio of the ro-vibrational band is fairly weak and thus
      the lower J ro-vibrational transitions can not be assigned with certainty. As a
      consequence the band center remains uncertain by 4 J or 0.17 cm(-1). For a more
      reliable assignment the sensitivity of the system has to be increased by at least
      one order of magnitude. The envisaged sensitivity increase of our experiment will
      be discussed along with the intention to perform terahertz observations of the
      low energetic bending ro-vibrational spectra. These sub-mm wave measurements will
      be carried out simultaneously with the IR measurements.

PMID- 12524114
TI  - Polymer complexes. XXXX. Supramolecular assembly on coordination models of mixed
      valence-ligand poly[1-acrylamido-2-(2-pyridyl)ethane] complexes.
AB  - The build-up of polymer metallic supramolecules based on homopolymer (1
      acrylamido-2-(2-pyridyl)ethane (AEPH)) and ruthenium, rhodium, palladium as well
      as platinum complexes has been pursued with great interest. The homopolymer shows
      three types of coordination behaviour. In the mixed valence paramagnetic
      trinuclear polymer complexes [(11)+(12)] in the paper and in mononuclear polymer
      complexes (1)-(5) it acts as a neutral bidentate ligand coordinating through the
      N-pyridine and NH-imino atoms, while in the mixed ligand diamagnetic poly
      chelates, which are obtained from the reaction of AEPH with PdX2 and KPtCl4 in
      the presence of N-heterocyclic base consisting of polymer complexes (9)+(10), and
      in monouclear compounds (6)-(8), it behaves as a monobasic bidentate ligand
      coordinating through the same donor atoms. In mononuclear compounds (13)+(14) it
      acts as a monobasic and neutral bidentate ligand coordinating only through the
      same donor atoms. Monomeric distorted octahedral or trimeric chlorine-bridged,
      approximately octahedral structures are proposed for these polymer complexes. The
      poly-chelates are of 1:1, 1:2 and 3:2 (metal-homopolymer) stoichiometry and
      exhibit six coordination. The values of ligand field parameters were calculated.
      The homopolymer and their polymer complexes have been characterized
      physicochemically.

PMID- 12524115
TI  - Effect of ligand structure on synergism in Tb3+-aromatic acid complexes:
      fluorescence lifetime studies.
AB  - The fluorescence of Tb3+ sensitized by aromatic carboxylic acid ligands (benzoic,
      monomethylphthalic, monomethylterephthalic, trimesic, terephthalic, isophthalic,
      phthalic and mellitic acids) and the synergism displayed by these complexes when
      treated with TOPO/Triton X-100 have been studied by measuring lifetimes of Tb3+
      emission. The lifetime of Tb3+ fluorescence was not significantly altered
      following complex formation with aromatic carboxylic acids, even though a
      significant enhancement in the Tb3+ fluorescence intensity was observed in every
      single case. However, when these Tb3+-aromatic acid complexes were treated with
      TOPO/Triton X-100, the lifetimes of the Tb3+ fluorescence increased markedly, but
      only with certain acids. Interestingly, even amongst the acids that showed an
      increase in lifetime with TOPO/Triton X-100, the lifetimes as a function of the
      pH of the solution was strongly dependent on the structure of the ligand. These
      differences and the reasons for such behavior are discussed, which shed light on
      the role of the structure of the ligand on the synergism process.

PMID- 12524116
TI  - Unusual emissions from low-concentrated porphyrin solutions.
AB  - This contribution presents fluorescence measurements from highly diluted
      tetratolylporphyrin (TTP) solutions where acetone has been chosen as solvent. The
      concentrations of the solutions ranged from 10(-8) to 10(-14) M. Apart the normal
      S1-S0 fluorescence a new broad emission was recorded below 10(-8) M. This new
      emission blue-shifted to the S1-S0 fluorescence covered the spectral range
      between 19000 and 14000 cm(-1). Within the dilution series, both the S1-S0
      porphyrin fluorescence and the new emission exhibited a remarkably non-linear
      concentration-dependence. In the case in which the aggregate emission was strong,
      little S1-S0 emission could be detected and vice versa. The intensity maximum of
      the broad emission was detected from a 10(-13) M solution. The supplementary
      fluorescence was attributed to the presence of assembled molecules. This
      assumption was established by comparing the measurements with those obtained from
      1:1 acetone water solvent mixtures in which the formation of aggregates had been
      formerly proven. The emission originating from the formation of aggregates was
      interpreted by a qualitative model considering the energy levels of J-aggregated
      porphyrins.

PMID- 12524117
TI  - Solvent effects on infrared spectra of 2-acetylthiophene in organic solvents.
AB  - Infrared spectroscopy studies of 2-acetylthiophene (ACTH) in 18 different organic
      solvents, both polar and non-polar, were undertaken to investigate the solvent
      solute interactions. The frequencies of carbonyl stretching vibration
      upsilon(C=O) of ACTH were correlated with the properties such as the solvent
      acceptor number (AN) and the linear solvation energy relationships (LSER). The
      solvent-induced stretching vibration frequency shifts showed a better correlation
      with the LSER than the AN. A six-membered ring-like hydrogen bonding structure
      was presented and the solvent effects of ACTH in alcohol solvents were
      investigated in detail.

PMID- 12524118
TI  - Solvation of AlCl3 in deuterated acetonitrile studied by means of vibrational
      spectroscopy.
AB  - Large blue shifts of the nu2 C=N stretch, nu4 Cz.sbnd;C stretch, and nu8 CCN
      deformation bands of CD3CN are observed in the infrared and Raman spectra of
      CD3CN solution of AlCl3, resulting from the donor-acceptor interactions of CD3CN
      with the Lewis acid. The Raman spectrum in the nu2 region shows further details;
      two new bands emerge on the blue side of the nu2 band of free CD3CN, and the
      ratio in intensity of the two bands also changes with concentration. Parallel to
      the nu2 region, similar new bands are observed on the blue sides of the nu4 and
      nu8 bands of free CD3CN. The solvation number of AlCl3, determined from the Raman
      intensities of the C=N stretch bands for free and coordinated CD3CN, increases
      from 1.54 to about 1.7 with decreasing concentration, indicating that various
      complexes with different numbers of coordinated acetonitrile coexist in the
      solution. The strong hydrogen bonds formed between the CD3 group and the chlorine
      atoms of the solute result in a large band appearing on the low frequency side of
      the nu1 CD3 symmetric stretch of free CD3CN.

PMID- 12524119
TI  - Thermal lens spectrum of organic dyes using optical parametric oscillator.
AB  - The wavelength dependence of thermal lens signal from organic dyes are studied
      using dual beam thermal lens technique. It is found that the profile of thermal
      lens spectrum widely differ from the conventional absorption spectrum in the case
      of rhodamine B unlike in the case of crystal violet. This is explained on the
      basis of varying contribution of nonradiative relaxations from the excited
      vibronic levels.

PMID- 12524120
TI  - Theoretical studies on vibrational spectra of mixed cyanide-halide complexes of
      platinum(IV) and palladium(IV).
AB  - The vibrational spectra of mixed cyanide-halide complexes, M(CN)4X 2 2- and
      M(CN)5X2- (M=Pt and Pd; X=F, Cl, Br and I), have been systematically investigated
      by ab initio RHF, B3LYP and MP2 methods with LanL2DZ and SDD basis sets. The
      calculated vibrational frequencies of platinum complexes are evaluated via
      comparison with the experimental values. In the infrared frequency region, the C-
      N stretching vibrational frequencies calculated at B3LYP level with two basis
      sets are in good agreement with the observed values with deviations, -16-4 cm(-1)
      for Pt(CN)4X 2 2- and -18 to -2 cm(-1) for Pt(CN)5X2-. However, in far-infrared
      region, the results obtained at RHF level are better than those calculated at
      B3LYP and MP2 levels. For RHF/SDD method, the deviations for Ptz.sbnd;X and
      Ptz.sbnd;C stretching vibrational frequencies are -14-1 and -12 to -2 cm(-1) in
      the complex Pt(CN)4X2 2-, -19 to -11 and -15-14 cm(-1) in the Pt(CN)5X2- complex,
      respectively. The vibrational frequencies of palladium(IV) and some platinum(IV)
      complexes that have not been experimentally reported are predicted.

PMID- 12524121
TI  - A study of peroxyoxalate-chemiluminescence of acriflavine.
AB  - The chemiluminescence arising from the reaction of bis(2,4,6
      trichlorophenyl)oxalate (TCPO) with hydrogen peroxide in the presence of
      acriflavine has been studied. The relationship between the chemiluminescence
      intensity and concentrations of TCPO, H2O2, acriflavine and the base sodium
      salicylate are reported. The kinetic parameters for the peroxyoxalate
      chemiluminescence (PO-CL) of acriflavine were evaluated from the computer fitting
      of the corresponding chemiluminescence intensity-time plots.

PMID- 12524122
TI  - Investigation of the diffusion coefficient of polymers and micelles in aqueous
      solutions using the Soret effect in cw-laser thermal lens spectrometry.
AB  - The concentration gradient (Soret effect) induced in cw-laser thermal lens
      spectrometry subsequently to the formation of the thermal gradient (thermal lens
      effect) has been investigated in aqueous solutions of various macromolecular
      species including micelles, mixed micelles and polymers. It is shown that the
      build-up of the concentration gradient is much shorter than that in classical
      Soret experiments, reaching steady-state values in less than 1 min. The time
      evolution of the Soret signal has been used to derive mass-diffusion times from
      which mass-diffusion coefficients were calculated. Our data are in agreement with
      previous results obtained from quasi-elastic light scattering studies for the
      micellar solutions and calculated from a known molecular weight-dependent power
      law for polymer solutions.

PMID- 12524123
TI  - Non-radiative depletion of the excited electronic states of 9-cyanoanthracene in
      presence of tetrahydronaphthols.
AB  - Both steady state and time resolved spectroscopic measurements reveal that the
      prime process involved in quenching mechanism of the lowest excited singlet (S1)
      and triplet (T1) states of the well known electron acceptor 9-Cyanoanthracene
      (9CNA) in presence of 5,6,7,8-tetrahydro-1-naphthol (TH1N) or 5,6,7,8-tetrahydro
      2-naphthol (TH2N) is H-bonding interaction. It has been confirmed that the
      fluorescence of 9CNA is not at all affected in presence of 5,6,7,8-tetrahydro-2
      methoxy naphthalene (TH2MN) both in non-polar n-heptane (NH) and highly polar
      acetonitrile (ACN) media. This indicates that the H-bonding interaction is
      crucial for the occurrence of the quenching phenomenon observed in the present
      investigations with TH1N (or TH2N) donors and 9CNA acceptor. In ACN solvent both
      contact ion-pair (CIP) and solvent-separated (or dissociated) ions are formed due
      to intermolecular H-bonding interactions in the excited electronic states (both
      singlet and triplet). In NH environment due to stronger H-bonding interactions,
      the large proton shift within excited charge transfer (CT) or ion-pair complex, 1
      or 3(D+-H...A-), causes the formation of the neutral radical, 3(D+H-A)*, due to
      the complete detachment of the H-atom. It is hinted that both TH1N and TH2N due
      to their excellent H-bonding ability could be used as antioxidants.

PMID- 12524124
TI  - Inelastic neutron scattering (INS) studies on 2,5-dihydroxy-1,4-benzoquinone
      (DHBQ).
AB  - Inelastic neutron scattering (INS) spectra of solid 2,5-dihydroxy-1,4
      benzoquinone were measured and compared with IR and Raman data. The INS spectrum
      is very well reproduced in the region below 1000 cm(-1) by DFT calculations on
      the B3LYP/6-311++G** level using Gaussian and Climax programs. To get a better
      agreement one should take into account additional interactions of OH groups in
      the solid state leading to an increase of the gamma(OH) frequency and to a
      decrease of frequencies for modes in which the delta(OH) participates. The
      studies of the deuterated compound in IR enabled to correct the assignment of
      gamma(OH) vibrations. Highly asymmetric nu(OH) band observed in IR spectrum with
      sharp maximum at about 3300 cm(-1) is discussed in terms of a stochastic approach
      to the analysis of hydrogen bonded systems.

PMID- 12524125
TI  - Theoretical interpretation of electronic absorption and emission transitions in 9
      acridinones.
AB  - Stationary absorption, fluorescence excitation and fluorescence spectra for
      9(10H)-acridinone, 9(10-methyl)-acridinone, 2-methyl-9(10-methyl)-acridinone, 2
      nitro-9(10-methyl)-acridinone, 9(10-ethyl)-acridinone and 9(10-phenyl)-acridinone
      dissolved in 1,4-dioxane, methyl alcohol or acetonitrile, as well as the
      available spectral characteristics reported by others were compared with those
      predicted theoretically at the semi-empirical PM3/CI (including the solvent
      effect within the COSMO model) or PM3/S levels of theory, in order to interpret
      spectral features of the compounds, i.e. the energies and probabilities of S0-
      >Sn, S0-->T1, T1-->T2, S1-->S0, T1-->S0 and S1-->T1 transitions. Calculations at
      the PM3 and PM3/CI levels of theory enabled the structural changes accompanying
      S0-->S1, S1-->T1 and T1-->S0 transitions to be investigated; they yielded,
      moreover, basic physicochemical characteristics of the molecules in the ground
      and excited electronic states. Theoretically predicted dipole moments and charge
      distributions in the S0, S1 and T1 states provided further insight into the
      nature of electronic transitions in 9-acridinones. The predicted characteristics
      correlate quite well with the available experimental ones, thus providing
      confirmation of the utility of theory in predicting the features of
      electronically excited molecules and interpreting the electronic transitions
      occurring in them.

PMID- 12524126
TI  - Fluorescence characteristics of protonated form of 6-hydroxyquinoline in Nafion
      film.
AB  - Fluorescence characteristics of 6-hydroxyquinoline (6-HQ) have been studied at
      room temperature in Nafion(R) film by steady state and nano-second time-resolved
      fluorescence spectroscopy. The fluorescence spectrum exhibits single emission
      band corresponding to the protonated form of 6-HQ in this matrix. However, the
      decay fits with two or three exponential functions depending on the emission
      wavelength monitored. At blue edge of the emission, the decay fits to three
      exponential function, whereas at longer wavelengths, the decay fits to bi
      exponential function. Two tentative mechanisms have been proposed to explain the
      experimental data, viz. a closely lying charge transfer state (CT) or an excited
      state proton transfer (ESPT) process. The photophysical parameters appear to be
      sensitive to the change in microstructure due to swelling of the membrane by the
      solvents.

PMID- 12524127
TI  - An investigation on a broad infrared band with the maximum at approximately 1300
      cm(-1) in magnesia cement, phase 3.
AB  - In magnesia cement, phase 3, a broad and strong infrared band was observed with
      the maximum at approximately 1300 and 1050 cm(-1) in the H and D systems,
      respectively. To clarify the origin of the 1300 cm(-1) band the temperature
      dependency of the infrared spectra of the H system was observed and the spectra
      analyzed on the basis of a strong vibrational coupling of the OH stretching with
      lattice modes. The fitting was quite well, giving rise to the origin of the 1300
      cm(-1) band of the OH stretching.

PMID- 12524128
TI  - Vibrational spectra of diethylsulfoxide.
AB  - FT IR and Raman spectroscopic studies of pure diethylsulfoxide (DESO) in the
      liquid and in the solid states and its solutions in various solvents have been
      performed. Analysis of SO- and CH-stretching regions in a wide range of
      concentration shows that the bands may be fitted satisfactorily by considering
      seven components. In addition, fundamental frequencies have been assigned using
      ab initio calculations at the RHF/3-21G* levels. The results obtained confirm a
      viewpoint on a self-associative structure of DESO, and support the hypothesis of
      the existence of different types of intermolecular associates including both
      dipole-dipole and hydrogen bonding mechanisms.

PMID- 12524129
TI  - Surface-enhanced Raman scattering of some water insoluble drugs in silver
      hydrosols.
AB  - An extraction method has been used to obtain surface-enhanced Raman scattering
      (SERS) spectra of water insoluble drugs such as aspirin, salicylic acid,
      acetaminophen, and vitamin A acid. This method is based on the strong affinity of
      the sample molecules to the silver particle surfaces. Results from the present
      study indicate that the method can be extended to identify and analyze many other
      water insoluble compounds by SERS. The high sensitivity of SERS and the linear
      calibration curve make it feasible in the trace quantitative analysis; the low
      limit of detection is comparable or better than those of calorimetric and
      spectrophotometric methods.

PMID- 12524130
TI  - Influence of weak and strong donor groups on the fluorescence parameters and the
      intersystem crossing rate constant.
AB  - The absorption and fluorescence properties of 35 specially selected methyl and
      stronger donor substituted benzene, naphthalene, biphenyl, anthracene and 2
      azaanthracene compounds are studied experimentally (at 293 K) and quantum
      chemically. The fluorescence quantum yields, gamma, and decay times, tauf, for
      deaerated and non-deaerated solutions are measured. The oscillator strength, fe,
      natural lifetime, tauf 0 and fluorescence and intersystem crossing rate
      constants, kf and kST, are calculated for each compound. The orbital nature of
      the lowest excited singlet state, S1, is determined. The investigation shows that
      the introduction of methyl groups onto aromatic compounds may produce different
      effects. The symmetry and hence kST and kf may change. As a result, gamma will
      also change. Steric hindrance, possibly due to the CH3 group, will decrease kf
      while increasing kST. In cases where the introduction of the methyl group leaves
      the symmetry unchanged, there is a slight increase in kST and a slight decrease
      in kf. This effect is cumulative (more CH3 groups lead to a greater decrease in
      gamma) and can be explained by the torsional vibrations of the methyl groups. The
      introduction of strong donor groups usually produces dramatic changes. kST always
      increases, as does kf and the increase in kf is usually greater. Hence, gamma
      usually increases, sometimes dramatically. The nature of the S1 state changes
      from pipi* (for an aromatic molecule) to pil,pi*. There are three reasons for the
      observed increase in kST: (i) a decrease in symmetry; (ii) the internal heavy
      atom effect; and (iii) an improved mixing of the S(1pil,pi*) state with Ti
      states. It is also found that, in many cases, the effect of methyl and stronger
      donor groups on the fluorescence parameters and kST depends on the position of
      substitution, as well as changes in the molecular symmetry. The substituent
      groups have different effects on the p- and alpha-bands. The fluorescence
      parameters obtained and trends observed may be useful for different theoretical
      and practical purposes.

PMID- 12524131
TI  - Modified UBFF calculations of the alpha-L-fucopyranose molecule in the
      crystalline state.
AB  - Normal co-ordinate analysis has been realised in the crystalline state using a
      modified Urey-Bradley-Shimanouchi force field combined with an intermolecular
      potential energy function that includes van der Waals interactions, some
      electrostatic terms and an explicit hydrogen bond function. The vibrational
      spectra of the alpha-L-fucose molecule have been recorded in the crystalline
      state, in the 4000-500 cm(-1) spectral region for the mid-IR spectra, in the 500
      100 cm(-1) spectral region for the far-IR spectra, and in the 4000-20 cm(-1)
      spectral range for Raman spectra. These spectra constitute the experimental
      support for the establishment of a force field for the molecule in the
      crystalline state through a normal co-ordinate analysis.

PMID- 12524133
TI  - The photodimerisation of the alpha- and beta-forms of trans-cinnamic acid: a
      study of single crystals by vibrational microspectroscopy.
AB  - Infrared and Raman microspectroscopy have been used to follow the
      photodimerisation reactions of single crystals, the alpha- and beta-forms of
      trans-cinnamic acid. This approach allows the starting materials and products
      alpha-truxillic acid that has Ci symmetry and beta-truxinic acid, which has Cs
      symmetry-to be identified. It also allows the topotactic nature of the reaction
      to be confirmed. Attempts to produce the poorly-defined unreactive gamma-form of
      trans-cinnamic acid resulted only in a mixture of the alpha- and beta-forms. The
      findings suggest a wide role for these spectroscopic methods in monitoring solid
      state organic reactions.

PMID- 12524132
TI  - Structure-function relationships in the neurotoxin Vipoxin from the venom of
      Vipera ammodytes meridionalis.
AB  - The neurotoxic complex Vipoxin is the lethal component of the venom of Vipera
      ammodytes meridionalis, the most toxic snake in Europe. It is a complex between a
      toxic phospholipase A2 (PLA2) and a non-toxic and catalytically inactive protein,
      stabilizing the enzyme and reducing the activity and toxicity. Structure-function
      relationships in this complex were studied by spectroscopic methods. A good
      correlation between the ionization behaviour and accessible surface area (ASA) of
      the tyrosyl residues was observed. In the toxic PLA2 subunit phenolic groups
      participate in H-bonding network that stabilizes the catalytically and
      pharmacologically active conformation. The tryptophan fluorescence decay of
      Vipoxin is well fitted by two exponentials with lifetimes of 0.1 (54%) and 2.5
      (46%) ns. W20P, W31P and W31I are located in the interface between the two
      subunits and participate in hydrophobic interactions stabilizing the complex.
      Dissociation of the complex leads to a transition of the tryptophans from
      hydrophobic to hydrophilic environment, which influences mainly tau2. The longer
      lifetime is more sensitive to the polarity of the environment. Circular dichroism
      measurements demonstrate that the two components of the neurotoxin preserve their
      secondary structure after dissociation of the complex. The results of the
      spectroscopic studies are in accordance with a mechanism of blockade of
      transmission across the neuromuscular junctions of the breathing muscles by
      interaction of a dissociated toxic PLA2 with a membrane. The loss of toxicity is
      connected with slight changes in the secondary structure of PLA2. CD studies also
      show a substantial contribution of disulfide bonds to the stability of the
      neurotoxic complex and its components.

PMID- 12524134
TI  - Vibrational frequencies and structural determinations of urazole.
AB  - The vibrational frequencies and corresponding normal mode assignments of urazole
      are examined theoretically using the Gaussian98 set of quantum chemistry codes.
      All normal modes were successfully assigned to one of eight types of motion (N--H
      stretch, C=O stretch, C--N stretch, N--N stretch, N--H bend, C=O bend, N--C--N
      bend, ring torsion) utilizing the C2 symmetry of the molecule. The molecular
      orbitals of urazole are examined. The simultaneous double inversion of the amine
      groups in urazole is also examined.

PMID- 12524135
TI  - Studies on the synthesis of 5-(p-aminobenzylidene)-rhodanine and its properties.
AB  - A new analytical reagent 5-(p-aminobenzylidene)-rhodanine (ABR) was synthesized.
      The acidic dissociation constant of ABR has been determined. The properties, the
      acid-base behavior of ABR and the reactions of ABR with metallic ions have been
      studied. The color reactions of the reagent with Pd(II), Au(III), Ag(I), Ru(III),
      Hg(II) and Cu(II) are studied in detail. The composition of Pd(II)-ABR, Au(III)
      ABR and Ag(I)-ABR complexes were discussed.

PMID- 12524136
TI  - Wf-536 prevents tumor metastasis by inhibiting both tumor motility and angiogenic
      actions.
AB  - The signaling pathway of Rho and Rho-associated coiled-coil forming protein
      kinase (ROCK) is involved in tumor metastasis. In the present study, we
      investigated the suppressive effect of a novel inhibitor of ROCK, Wf-536 [(+)-(R)
      4-(1-Aminoethyl)-N-(4-pyridyl) benzamide monohydrochloride], on spontaneous tumor
      metastasis in vivo and analyzed its action on tumor cell motility and
      angiogenesis to clarify its action mechanism. Wf-536 (0.3-3 mg/kg/day) was found
      to inhibit Lewis lung carcinoma (LLC) metastasis and LLC-induced angiogenesis in
      orally treated mice; in vitro, it inhibited both invasion and migration by LLC
      cells and invasion, migration, and formation of capillary-like tubes on Matrigel
      by endothelial cells, without cytotoxicity or anti-proliferative action in either
      cell type. We conclude that Wf-536 has tumor anti-metastatic activity which may
      depend on inhibition of tumor motility and angiogenesis. The findings support its
      further clinical development as an anti-metastatic agent.

PMID- 12524137
TI  - Ethanol differently affects stress protein and HERG K+ channel expression in SH
      SY5Y cells.
AB  - Ethanol is known to be neurotoxic. Protective mechanisms, however, are activated
      upon ethanol induction of the glucose-regulated stress proteins (GRPs), GRP78 and
      GRP94. These endoplasmic reticulum-residing chaperones are known to be involved
      in channel subunit assembly. The GRP and human-ether-a-gogo-related gene (HERG)
      K(+)-channel expression were monitored in short- and long-term ethanol incubation
      experiments using the human neuroblastoma cell line SH-SY5Y. mRNA of the stress
      proteins and protein levels of the GRPs and HERG were determined using Northern
      and Western blot methods. Short-term ethanol incubation caused a transient
      increase of GRP transcripts. Protein levels of GRP94 decreased in chronic
      experiments, whereas GRP78 did not change. HERG followed the same kinetics as
      GRP94 with a constant down-regulation. The coordinate down-regulation of GRP94
      and HERG implies the specific involvement of the endoplasmic reticulum chaperone
      GRP94 and HERG, but not GRP78, in a process of cell adaptation.

PMID- 12524138
TI  - Effects of rhizoxin, a microbial angiogenesis inhibitor, on angiogenic
      endothelial cell functions.
AB  - Our previous study revealed that rhizoxin ([1S
      [1R*,3R*,5S*,8R*(1R*,2S*,3E,5E,7E),10R*,11S*,13S*,14E,16S*,17S*]]-10-hydroxy-8-[2
      methoxy-1,3,7-trimethyl-8-(2-methyl-4-oxazolyl)-3,5,7-octatrienyl]-11,16-dimethyl
      4,7,12,18-tetraoxatetracyclo[15.3.1.03,5.011,13]heneicos-14-ene-6,19-dione) has a
      potent inhibitory effect on in vivo angiogenesis. However, little is known
      regarding the mechanism by which rhizoxin exhibits antiangiogenic activity. In
      this study, we examined its effects on the functions of endothelial cells
      associated with neovascular formation in vivo, using cultured vascular
      endothelial cells. Rhizoxin concentration-dependently inhibited the proliferation
      of bovine carotid artery endothelial cells, human umbilical vein endothelial
      cells and human dermal microvascular endothelial cells, the IC(50) values being
      7, 5 and 0.4 nM, respectively. In addition, it reduced the extracellular
      plasminogen activator level in bovine vascular endothelial cells in the low nM
      range, and suppressed the migration of human dermal microvascular endothelial
      cells in the pM range. Furthermore, it blocked the tubular morphogenesis of human
      umbilical vein endothelial cells and human dermal microvascular endothelial cells
      on Matrigel in a concentration-dependent manner; the IC(50) values being 40 and
      130 pM, respectively. These results suggest that rhizoxin exhibits antiangiogenic
      activity through the combined inhibition of some functions of endothelial cells
      responsible for induction of in vivo angiogenesis.

PMID- 12524139
TI  - The effects of delta9-tetrahydrocannabinol physical dependence on brain
      cannabinoid receptors.
AB  - The effects of chronic Delta(9)-tetrahydrocannabinol on cannabinoid receptor
      levels and receptor-G-protein coupling were investigated. Male Sprague-Dawley
      rats were infused continuously with low or high dose regimens of Delta(9)
      tetrahydrocannabinol or vehicle for 4 days. Following treatment, rats were
      sacrificed for cannabinoid CB(1) receptor binding analysis or challenged with the
      cannabinoid CB(1) receptor antagonist, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1
      (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR141716A). The rats
      receiving Delta(9)-tetrahydrocannabinol exhibited antagonist-precipitated
      withdrawal signs. Each brain region (cerebellum, cortex, hippocampus and basal
      ganglia) from high-dose rats showed 30-70% decreases in [3H] (-)-cis-3-[2-hydroxy
      4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxyphenyl)cyclohexanol (WIN55212-2)
      B(max) values, indicating receptor down-regulation. Most regions showed decreased
      WIN55212-2-stimulated [35S]guanosine-5'-O-3-thiotriphosphate (GTPgammaS) binding,
      indicating desensitization of cannabinoid CB(1) receptors. Additional receptor
      binding assays in cerebellar membranes showed a significantly greater decrease in
      agonist than in antagonist B(max) values, indicating a lower fraction of coupled
      receptors after treatment. Concentration-effect analysis of five agonists
      revealed that the treatment resulted in greater decreases in the efficacy of low
      efficacy agonists.

PMID- 12524140
TI  - Characterization of sabiporide, a new specific NHE-1 inhibitor exhibiting slow
      dissociation kinetics and cardioprotective effects.
AB  - Sabiporide, a new benzoguanidine, was characterized on fibroblasts stably
      expressing the Na(+)/H(+) exchanger isoforms NHE-1, NHE-2 and NHE-3. 22Na(+)
      uptake experiments show that this compound possesses a K(i) of 5+/-1.2 x 10(-8) M
      for NHE-1, and discriminates efficiently between the NHE-1, -2 and -3 isoforms
      (K(i) for NHE-2: 3+/-0.9 x 10(-6) M, and K(i)>1 mM for NHE-3). Similar K(i)
      values are obtained on rat cardiomyocytes and human platelets expressing NHE-1
      (K(i)'s of 7+/-1 x 10(-9) and 2.7+/-0.4 x 10(-8) M respectively). Interestingly,
      when compared with amiloride and cariporide, sabiporide inhibition persists even
      after this molecule had been rinsed out (half time of 7 h for sabiporide, and of
      1 and 2.5 min for amiloride and cariporide, respectively), the decay of all these
      molecules exhibiting a complex multiexponential behavior. Thus, sabiporide, which
      possesses remarkable cardioprotective properties, is a specific NHE-1 inhibitor
      possessing unique binding kinetics.

PMID- 12524141
TI  - Functional characterization of the adenosine receptor contributing to
      glycogenolysis and gluconeogenesis in rat hepatocytes.
AB  - The adenosine receptor subtype mediating glucose production by glycogenolysis and
      gluconeogenesis was studied in primary cultured rat hepatocytes. Adenosine and
      adenosine agonists caused cyclic AMP accumulation in rat hepatocytes. The order
      of potency was 5'-N-ethylcarboxamidoadenosine (NECA)>R(-)-N(6)-(2
      phenylisopropyl)adenosine (RPIA)>adenosine>2-[p-(carboxyethyl)phenylethylamino]
      5'-N-ethylcarboxamidoadenosine (CGS21680). Furthermore, adenosine agonists
      stimulated glycogenolysis and gluconeogenesis. The order of potency was
      NECA>RPIA>CGS21680. The rank order of potency is typical for adenosine A(2B)
      receptors. Glycogenolysis stimulated by NECA was fully inhibited by nonselective
      adenosine antagonists, 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5
      amine (CGS15943). However, the adenosine A(2A) receptor-selective antagonist, 8
      (3-chlorostyryl)caffeine (CSC), and the adenosine A(1) receptor-selective
      antagonist, (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-alpha]pyridin-3-yl)acryloyl]-2
      piperidine ethanol (FK453), had a low inhibitory potency. A strong correlation
      was found between the inhibitory effect of adenosine antagonists on NECA-induced
      glucose production and that on intracellular cyclic AMP generation in rat
      hepatocytes. Our results suggest that adenosine stimulates cyclic AMP formation
      and regulates glycogenolysis and gluconeogenesis, most likely through the
      adenosine A(2B) receptor subtype in rat hepatocytes.

PMID- 12524142
TI  - Cocaine inhibits 5-HT3 receptor function in neurons from transgenic mice
      overexpressing the receptor.
AB  - Studies have shown that cocaine alters the function of recombinant 5-HT(3)
      receptors and that behavioral responses to cocaine are affected by 5-HT(3)
      receptor ligands. However, the actions of cocaine on brain 5-HT(3) receptors have
      not been characterized because these receptors are not abundantly expressed in
      most neuronal populations. We examined the effect of cocaine on 5-HT(3) receptor
      function in cultured hippocampal neurons from transgenic mice overexpressing the
      receptor. Cocaine competitively inhibited 5-HT(3) receptors with an IC(50) of
      approximately 4 microM, indicating that brain 5-HT(3) receptors are important
      targets for the actions of this commonly abused substance.

PMID- 12524143
TI  - Excitatory and inhibitory amino acid changes during repeated episodes of ethanol
      withdrawal: an in vivo microdialysis study.
AB  - Changes in amino acid levels in the hippocampus during repeated ethanol
      withdrawal were studied. Wistar rats were made ethanol-dependent by 4-week vapour
      inhalation. After this first cycle of chronic ethanol treatment, rats underwent
      repeated and alternate cycles of 24 h of withdrawal followed by 1 week of chronic
      ethanol treatment. The microdialysis technique was used together with high
      performance liquid chromatography and electrochemical detection to separate and
      quantify different amino acids such as aspartate, glutamate, arginine, taurine,
      alanine and gamma-aminobutyric acid. During the first cycle of ethanol
      withdrawal, increases in glutamate, taurine and alanine levels were observed.
      During the third withdrawal period, further increases were detected in aspartate,
      glutamate, taurine and alanine in the comparison with levels in the control
      group. However, the arginine level during the third withdrawal period decreased
      when compared to that after the first withdrawal period. The results of this
      study demonstrate that excitatory amino acid levels increased with subsequent
      withdrawal periods.

PMID- 12524144
TI  - Suppression of hyperemia and DNA oxidation by indomethacin in cerebral ischemia.
AB  - We investigated antioxidative activity and the effect of indomethacin, an agent
      that inhibits cyclooxygenase, on extracellular glutamate and cerebral blood flow
      in cerebral ischemia in gerbils. Pre-ischemic administration of indomethacin (5
      mg/kg, i.p.) significantly rescued hippocampal CA1 neurons (9+/-6 cells/mm in the
      ischemia, 87+/-43 cells/mm in the indomethacin group, P<0.001). DNA fragmentation
      induced by ischemia was also examined using the terminal deoxynucleotidyl
      transferase-mediated UTP nick end labeling (TUNEL) method and indomethacin
      reduced TUNEL positive cells (140+/-21 in the ischemia, 99+/-31 in the
      indomethacin group, P<0.01). In addition, indomethacin attenuated the increase in
      hippocampal blood flow during reperfusion, but not increased extracellular
      glutamate by ischemia. Eight-hydroxydeoxyguanosine (8-OH-dG), a highly sensitive
      marker of DNA oxidation, was measured 90 min following ischemia using high
      pressure liquid chromatography. Indomethacin significantly decreased the level of
      ischemia-induced 8-OH-dG in the hippocampus (P<0.05). These results suggest that
      indomethacin may protect neurons by attenuating oxidative stress and reperfusion
      injury in ischemic insult.

PMID- 12524145
TI  - Prostanoid EP3 and TP receptors-mediated inhibition of noradrenaline release from
      the isolated rat stomach.
AB  - The postganglionic sympathetic nerves of the isolated rat stomach were
      electrically stimulated twice at 1 Hz for 1 min. Prostaglandin E(2) and ONO-AE
      248 (16S-9-deoxy-9beta-chloro-15-deoxy-16-hyfroxy-17,17-trimethylene-19,20
      didehydro prostaglandin F(2)) (an EP(3) receptor agonist) reduced the evoked
      noradrenaline release, while ONO-DI-004 (17S-2,5-ethano-6-oxo-17,20-dimethyl
      prostaglandin E(1)) (an EP(1) receptor agonist), ONO-AE1-259-01 (11,15-O-dimethyl
      prostaglandin E(2)) (an EP(2) receptor agonist) and ONO-AE1-329 [16-(3
      methoxymethyl)phenyl-omega-tetranor-3,7-dithia prostaglandin E(1)] (an EP(4)
      receptor agonist) had no effect. U-46619 (9,11-dideoxy-9alpha,11alpha
      methanoepoxy prostaglandin F(2alpha)) and I-BOP (7-[3-[3-hydroxy-4-(4
      iodophenoxy)-1-butenyl]-7-oxabicyclo[2,2,1] hept-2-yl]
      ,[1S[1alpha,2alpha(Z),3beta(1E,3S)4alpha]]-5-heptenoic acid) (TP receptor
      agonists) also reduced the noradrenaline release and these inhibitory effects
      were abolished by SQ-29548 (7-[3-[[2-[(phenylamino) carbonyl] hydrazino]methyl]-7
      oxabicyclo[2,2,1]hept-2-yl][1S(1alpha,2alpha(Z), 3alpha,4alpha]-5-heptenoic acid)
      (a TP receptor antagonist). The inhibitory effect of U-46619, but not ONO-AE-248,
      was abolished by pertussis toxin. These results suggest that the prostanoid EP(3)
      and TP receptors mediate the inhibition of gastric noradrenaline release; TP, but
      not EP(3), receptor-mediated inhibition is mediated by a pertussis toxin
      sensitive mechanism in rats.

PMID- 12524146
TI  - Up-regulated dopamine D1 receptor binding can be detected in vivo following
      repeated SCH 23390, but not SKF 81297 or 6-hydroxydopamine, treatments.
AB  - Three different pharmacological treatments, previously shown to cause dopamine D1
      receptor supersensitivity in rats, were studied for changes in the binding of R
      (+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH
      23390) labeled with carbon-11. Rats treated subchronically with the full dopamine
      D1 receptor agonist R/S-(+/-)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro
      1H-3-benzazepine (SKF 81297) showed no significant difference in dopamine D1
      receptor binding. Similarly, unilateral 6-hydroxydopamine lesioning, followed by
      apomorphine screening for contralateral rotation, failed to cause significant
      differences in the rat brain distribution of [11C]SCH 23390 in the lesioned
      versus the nonlesioned striatal sides. In contrast, repeated exposure with the
      dopamine D1 receptor antagonist SCH 23390 significantly enhanced the uptake of
      [11C]SCH 23390 in the dopamine D1 receptor-rich striatum and olfactory tubercles.
      These results demonstrate that [11C]SCH 23390 can significantly detect enhanced
      binding in rat brain regions expected to have up-regulated dopamine D1 receptors.
      The failure of [11C]SCH 23390 to reveal any differences after subchronic agonist
      or 6-hydroxydopamine treatments suggests that the behavioural supersensitization
      induced by these treatments is possibly due to changes to the high-affinity state
      or to components downstream of dopamine D1 receptors in the signal transduction
      pathway. The present study has implications for studies imaging dopamine D1
      receptors in neuropsychiatric disorders with abnormal dopamine stimulation using
      positron emission tomography.

PMID- 12524147
TI  - 14-Methoxymetopon, a very potent mu-opioid receptor-selective analgesic with an
      unusual pharmacological profile.
AB  - 14-Methoxymetopon is a potent opioid analgesic. When given systemically, it is
      approximately 500-fold more active than morphine. However, this enhanced potency
      is markedly increased with either spinal or supraspinal administration, where its
      analgesic activity is more than a million-fold greater than morphine. It was mu
      opioid receptor selective in binding assays and its analgesia was blocked only by
      mu-opioid receptor-selective antagonists. Yet, it had a different selectivity
      profile than either morphine or morphine-6beta-glucuronide. Unlike morphine, 14
      methoxymetopon was antagonized by 3-O-methylnaltrexone, it was sensitive to
      antisense probes targeting exons 1, 2 and 8 of the opioid receptor gene and was
      inactive both spinally and supraspinally in CXBK mice. Although it retarded
      gastrointestinal transit, it displayed a ceiling effect with no dose lowering
      transit by more than 65%, in contrast to the complete inhibition of transit by
      morphine. These finding demonstrate that 14-methoxymetopon is a highly potent mu
      opioid with a pharmacological profile distinct from that of the traditional mu
      opioid morphine.

PMID- 12524148
TI  - Immobilization stress-induced increment of lactate metabolism in the basolateral
      amygdaloid nucleus is attenuated by diazepam in the rat.
AB  - Using in vivo microdialysis technique, extracellular lactate levels were measured
      in the basolateral amygdaloid nucleus of the rat under immobilization stress.
      Immobilization stress (40 min) led to a tetrodotoxin-reversible increase in
      dialysate lactate levels. Diazepam (1.0 mg/kg, i.p.) reduced the ability of
      immobilization stress to increase lactate levels. Furthermore, the attenuation of
      the immobilization stress-induced increase of lactate levels by diazepam was
      antagonized by pretreatment with flumazenil (15 mg/kg, i.p.), a selective
      antagonist at benzodiazepine receptors. These findings suggest that
      immobilization stress increases lactate levels in rat basolateral amygdaloid
      nuclei, which is attenuated by stimulation of benzodiazepine receptors.

PMID- 12524149
TI  - Naloxone displacement at opioid receptor sites measured in vivo in the human
      brain.
AB  - We report the use of a sensitive non-tomographic positron detecting system to
      measure the dose-response curve of naloxone in human brain. [11C]Diprenorphine
      was administered to normal volunteers in tracer amounts and, 30 min later,
      various bolus doses of naloxone were given (1.5-160 microg/kg) intravenously and
      change in [11C]diprenorphine binding monitored over the next 30 min. We found
      that this method produced results consistent with existing data. It was observed
      that approximately 13 microg/kg of naloxone ( approximately 1 mg in an 80 kg man)
      was required to produce an estimated 50% receptor occupation. This is consistent
      with the clinical dose of naloxone used to reverse opiate overdose (0.4 mg-1.2
      mg).

PMID- 12524150
TI  - Prior exposure to the elevated plus-maze sensitizes mice to the acute behavioral
      effects of fluoxetine and phenelzine.
AB  - A single undrugged experience of the elevated plus-maze modifies future drug
      responses in the test. The present study investigated the effects of maze
      experience on the acute behavioral effects of the monoamine oxidase inhibitor
      phenelzine and the serotonin reuptake inhibitor fluoxetine. Phenelzine (2.5-12.5
      mg/kg) had no clear effect on plus-maze behavior in test-naive Swiss Webster
      mice, but dose-dependently increased anxiety-like behavior in maze-experienced
      subjects. Similarly, fluoxetine (5-20 mg/kg) produced non-significant trends for
      increased anxiety-like behavior in maze-naive mice, but significantly and dose
      dependently increased anxiety-like behavior and suppressed locomotor activity in
      maze-experienced mice. The anxiogenic effects of the benzodiazepine receptor
      inverse agonist N-methyl-beta-carboline-3-carboxamide (FG 7142) (20 mg/kg) was
      abolished by prior test experience, suggesting an alteration in gamma
      aminobutyric acid (GABA)/benzodiazepine receptor function with maze-experience.
      However, the benzodiazepine receptor antagonist flumazenil (5-20 mg/kg) produced
      a silent profile regardless of maze-experience. Present findings provide further
      evidence demonstrating that prior test history is a critical consideration in
      mouse studies of anxiety-related behavior.

PMID- 12524151
TI  - Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson
      and hemiparkinsonism.
AB  - The effects on motor behavior of a new potential dopamine stabilizer: 2-amino-6
      (N,N-di-n-propylamino)thiazolo[4,5-f]indan (GMC1111) were investigated in common
      marmosets with 6-hydroxydopamine lesions within the median forebrain bundle (12
      unilateral, 6 bilateral). GMC1111 was administered orally or subcutaneously
      (s.c.) to unilaterally 6-hydroxydopamine lesioned monkeys, either alone or
      together with s.c. injections of apomorphine (0.2 mg/kg) and the effect on
      rotational behavior was examined. GMC1111 (0.03-3.0 mg/kg) alone, orally or s.c.,
      did not induce rotational behavior. When apomorphine and GMC1111 were injected
      simultaneously, rotations were nearly abolished in three monkeys with a baseline
      apomorphine-induced rotation rate below 13/min, whereas GMC1111 did not modify
      the rotations in three high-rotating animals (>17/min). Oral administration of
      GMC1111 (1.0 and 3.0 mg/kg) abolished the apomorphine-induced rotations in
      another six unilaterally dopamine-denervated monkeys, indicating a good oral
      bioavailability. A low dose of GMC1111 (0.3 mg/kg) administered s.c. to marmosets
      with bilateral nigrostriatal lesions produced a reduction of Parkinson symptoms
      of approximately the same degree as with levodopa/benserazide (15/3.75 mg/kg),
      while higher doses of GMC1111 were less effective. When levodopa/benserazide was
      administered together with various doses of GMC1111 (0.3-3.0 mg/kg), the levodopa
      induced peak-dose dyskinesias were reduced with the highest dose of GMC1111 (3
      mg/kg). Taken together, GMC1111 modifies dopaminergic activity in a normalizing
      direction. Parkinson symptoms, as well as levodopa-induced dyskinesias are both
      reduced. This suggests the arrival of another member of the new dopamine
      stabilizer family.

PMID- 12524152
TI  - Effects of 5-HT1B receptor ligands microinjected into the ventral tegmental area
      on cocaine discrimination in rats.
AB  - Some recent data indicate a significant interaction between serotonin (5
      hydroxytryptamine; 5-HT) and dopamine in mesolimbic brain structures (e.g. the
      ventral tegmental area) which modulate the behavioral effects of cocaine in rats.
      The present study investigated the role of 5-HT(1B) receptors in the ventral
      tegmental area in the discriminative stimulus effects of cocaine in rats. Male
      Wistar rats were trained to discriminate cocaine (10 mg/kg, intraperitoneally
      (i.p.)) from saline (i.p.) in a two-choice, water-reinforced fixed-ratio 20
      procedure. After reaching the cocaine-saline discrimination criterion, the rats
      were stereotaxically implanted with bilateral cannulae in the ventral tegmental
      area and were then microinjected with selective 5-HT(1B) receptor ligands. In
      substitution studies, microinjections of the 5-HT(1B) receptor antagonist, 3-[3
      (dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide
      dihydrochloride (GR 55562; 0.1-1 microg/side), did not evoke cocaine-lever
      responding, whereas the 5-HT(1B) receptor agonist, 1,4-dihydro-3-(1,2,3,6
      tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one (CP 93129; 0.3-1
      microg/side), induced partial substitution for cocaine. Intra-tegmental
      microinjections with the 5-HT(1B) receptor antagonist, GR 55562 (0.1-1
      microg/side), before cocaine (5 mg/kg), which alone produced 98% cocaine-lever
      responses, decreased in a dose-dependent manner the discriminative stimulus
      effects of the psychostimulant. On the other hand, combination tests using a
      fixed dose of CP 93129 (0.3 or 1 microg/side), given into the ventral tegmental
      area prior to low systemic doses of cocaine (1.25-2.5 mg/kg), increased cocaine
      discrimination. These results seem to indicate that tegmental 5-HT(1B) receptors
      are necessary to express the discriminative stimulus effects of cocaine.

PMID- 12524153
TI  - Vascular reactivity to vasopressin during diabetes: gender and regional
      differences.
AB  - The isometric response to vasopressin of 2-mm-long segments of basilar, coronary,
      renal and tail arteries from male and female, control (normoglycemic) and
      streptozotocin-induced diabetic rats was studied. Vasopressin (10(-12)-3 x 10(-8)
      M) produced arterial concentration-dependent contraction, with a lower potency in
      coronary arteries from female than from male rats, and was similar for both
      genders in basilar, renal and tail arteries. This contraction was reduced by
      diabetes in basilar and coronary arteries, increased in renal arteries, and not
      modified in tail arteries, in both genders. Inhibition of nitric oxide synthesis
      with N(W)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) increased the
      contraction to vasopressin in coronary arteries from control female and diabetic
      female rats; as well as in renal arteries from control male and control female
      rats, but not in any other experimental group. Inhibition of cyclooxygenase with
      meclofenamate (10(-5) M) reduced the contraction to vasopressin in basilar
      arteries from diabetic female rats and in renal arteries from diabetic male rats,
      but not in any other experimental group. These results suggest that the response
      to vasopressin (a) has lower potency in female coronary arteries due to higher
      nitric oxide production; (b) is reduced by diabetes in basilar and coronary
      arteries from both genders, by mechanisms independent of nitric oxide and
      prostanoids; and (c) is increased by diabetes in renal arteries due to reduced
      production of nitric oxide in females, and to both reduced production of nitric
      oxide and increased production of prostanoids in males. Therefore, the effects of
      diabetes on vascular reactivity to vasopressin may differ between vascular beds,
      and the mechanisms underlay these effects may be distinct between genders.

PMID- 12524154
TI  - Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential.
AB  - Quercetin, a dietary-derived flavonoid, suppresses tumor growth in vitro and in
      vivo, and inhibits the activity of tyrosine kinase. The effects of quercetin on
      the angiogenic process were examined in this study. Quercetin was found to
      inhibit several important steps of angiogenesis including proliferation,
      migration, and tube formation of human microvascular dermal endothelial cells in
      a dose-dependent manner. Additionally, the effect of quercetin on endothelial
      cell proliferation was confirmed using human umbilical vein endothelial cells.
      The activity of quercetin on the proliferation of endothelial cells was stronger
      than that on A549, BEL-7402, MKN-45 tumor cells and NIH-3T3 fibroblast cells. The
      chicken chorioallantoic membrane assay revealed that addition of quercetin
      displayed an antiangiogenic effect in vivo. After exposure to quercetin, a
      decrease in the expression and activity of matrix metalloproteinase-2, which is
      involved in the angiogenic process of migration, invasion, and tube formation,
      was observed by reverse transcription-polymerase chain reaction (RT-PCR) and
      gelatin zymography. These findings suggest that quercetin has antiangiogenic
      potential and that this effect may be related to an influence on the expression
      and activity of matrix metalloproteinase-2.

PMID- 12524155
TI  - Mediation of nitric oxide from photosensitive stores in the photorelaxation of
      the rabbit corpus cavernosum.
AB  - Isolated rabbit corpus cavernosum relaxed in response to ultraviolet (UV) light
      (365 nm). The UV light-induced relaxation (photorelaxation) was diminished on
      repeated UV irradiation from 30.5+/-4.0% (the first photorelaxation) to 15.5+/
      2.7% (the last photorelaxation). Hydroxocobolamine of 100 microM and hemoglobin
      (Hb) of 10 microM, which are nitric oxide (NO) scavengers, and 10 microM 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a soluble guanylyl cyclase
      inhibitor, markedly reduced photorelaxation. However, 300 microM 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO)
      failed to inhibit photorelaxation. NaNO(2) and N(G)-nitro-L-arginine (L-NA) but
      not 3-nitro-L-tyrosine (3-NT) were found to be photosensitive in that these
      compounds are photolysed to release NO, as demonstrated by use of an amperometric
      NO probe; NO signals produced by 500 microM NaNO(2), and 500 microM L-NA were
      133.3+/-28.9 and 54.4+/-10.4 pA, respectively. Not 3-NT but the other compounds
      (all 200 microM) also enhanced photorelaxation of the cavernosal tissue. Based on
      these findings, the substance, which mediates photorelaxation, could be NO
      released from putative stores in the rabbit corpus cavernosum, and L-NA as well
      as NaNO(2) but not 3-NT produce NO under the influence of UV light.

PMID- 12524156
TI  - Docosahexaenoic acid inhibits cytokine-induced expression of P-selectin and
      neutrophil adhesion to endothelial cells.
AB  - Dietary polyunsaturated fatty acids, such as docosahexaenoic acid, may inhibit
      pathological processes involving endothelial cell activation. Herein, it was
      found that treatment of endothelial cells with docosahexaenoic acid dose
      dependently reduced neutrophil adhesion provoked by tumor necrosis factor-alpha
      (TNF-alpha). In fact, pretreatment with 100 microM of docosahexaenoic acid for 24
      h decreased TNF-alpha-induced neutrophil adhesion by 50%. Moreover, this
      pretreatment with docosahexaenoic acid (100 microM, 24 h) down-regulated TNF
      alpha-induced endothelial cell surface expression of P-selection by 75%.
      Importantly, immunoneutralization of P-selectin reduced neutrophil adhesion to
      TNF-alpha-activated endothelial cells by more than 50%, indicating a significant
      role of P-selectin in this model. On the other hand, CXC chemokines, i.e.
      macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil
      chemoattractant (KC), are also important regulators of neutrophil activation and
      adhesion. However, pretreatment with docosahexaenoic acid had no effect on TNF
      alpha-provoked production of MIP-2 and KC in endothelial cells. Our study provide
      evidence that docosahexaenoic acid inhibits expression of P-selectin and
      subsequent adhesion of neutrophils to endothelial cells in response TNF-alpha,
      which may help explain the anti-inflammatory effects exerted by docosahexaenoic
      acid.

PMID- 12524157
TI  - Postsynaptic firing produces long-term depression at inhibitory synapses of rat
      visual cortex.
AB  - High-frequency activation of excitatory synapses produces long-term depression
      (LTD) at inhibitory synapses in rat visual cortex. The LTD generation mechanism
      was studied by recording inhibitory postsynaptic potentials from layer V cells in
      response to layer IV stimulation under pharmacological blockade of excitatory
      synaptic transmission. LTD occurred after depolarizing current pulses applied to
      postsynaptic cells elicited repetitive firing. LTD induction was facilitated by a
      bath application of an L-type Ca(2+) channel activator, 1,4-Dihydro-2,6-dimethyl
      5-nitro-4-[2-(trifluoromethyl) phenyl]-3-pyridinecarboxylic acid, methyl ester
      (BAY K 8644), while it was prevented by either the bath application of L-type
      Ca(2+) channel blocker nifedipine or postsynaptic loading of Ca(2+) chelator 1,2
      bis-(o-aminophenoxy)ethane-N,N,N',N',-tetraaceticacid (BAPTA). These results
      suggest that LTD induction is at least partly mediated by Ca(2+) entry through L
      type Ca(2+) channels in association with postsynaptic action potentials.

PMID- 12524158
TI  - Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease.
AB  - Oxidative stress is widely thought to contribute significantly to the
      pathogenesis Parkinson's disease (PD). Given the role of glutathione S
      transferases (GSTs) in the conjugation of electrophiles and protection against
      reactive oxygen species, genes encoding the GSTs have been considered candidates
      for association studies of PD. We tested for associations between genotypes of
      GSTM1(homozygous deletion vs. non-deleted), GSTT1(homozygous deletion vs. non
      deleted), and GSTP1 (Ile104Val and Ala113Val) and PD in a case-control study of
      214 idiopathic PD cases and 330 age- and gender-matched, unrelated controls of
      Caucasian ethnicity. No significant associations with any of the GST genotypes
      were observed. However, there was a marginally significant difference in the
      distribution of GSTP1 104 genotypes between cases and controls (P=0.07), with an
      excess of Ile104Val heterozygotes found among cases (odds ratio (OR)=1.43; 95%
      Confidence Interval (CI): 0.98-2.08). This difference in the genotype
      distribution was strongest among smokers (OR for heterozygote=1.92; 95% CI: 1.12
      3.29) versus non-smokers and among males (OR for heterozygote=1.99; 95% CI: 1.24
      3.19) versus females. The distribution of GSTP1 Ile104Val and Ala113Val
      haplotypes did not differ between cases and controls. Taken together, these
      results suggest a potentially minor role of GSTP1 in PD, but do not give evidence
      for associations with either GSTM1 or GSTT1.

PMID- 12524159
TI  - Overexpression and RNA interference of Ap-cyclic AMP-response element binding
      protein-2, a repressor of long-term facilitation, in Aplysia kurodai sensory-to
      motor synapses.
AB  - cyclic AMP-response element binding protein-2 (CREB2) is a member of the
      CREB/transcription factor (CREB/ATF4) family. CREB2 is a transcription factor
      known to be involved in Aplysia long-term facilitation. To further examine the
      role of ApCREB2 on long-term synaptic facilitation, we isolated ApCREB2 from
      Aplysia kurodai in full-length cDNA library, and found that the overexpression of
      ApCREB2 blocked 5-hydroxytryptamine (5-HT)-induced long-term synaptic
      facilitation in Aplysia sensory-to-motor synapses. Furthermore, a single pulse of
      5-HT, which normally induces only short-term facilitation, in the presence of
      ApCREB2 inhibition by RNA interference, induced long-term facilitation in Aplysia
      sensory-to-motor synapses. These results suggest that ApCREB2 is a functional
      repressor of long-term facilitation in Aplysia sensory-to-motor synapses.

PMID- 12524160
TI  - Serotonin transporter-linked promoter region polymorphism and personality traits
      in a Japanese population.
AB  - Serotonin transporter gene may play a critical role in a regulation of mood and
      other aspects of mental status. A large number of association studies have
      investigated a correlation between the polymorphism in the serotonin transporter
      linked promoter region (5-HTTLPR) and anxiety-related personality traits. The
      results, however, have been inconsistent. Heterogeneity of subjects regarding
      gender, occupation, social-class and other environmental factors, in addition to
      effects of other genes, might have confounded the results. Here, we studied an
      association between the 5-HTTLPR polymorphism and personality traits in primarily
      female (78%) healthy subjects (n=244), who had homogeneous backgrounds regarding
      ethnicity (Japanese) and occupation. Personality traits of the subjects were
      assessed with the revised NEO Personality Inventory. No significant association
      was observed between the polymorphism and neuroticism or other personality
      traits, in all subjects, all females (n=190) or female nurses (n=159). Thus, our
      findings provided no evidence for an association between the 5-HTTLPR
      polymorphism and anxiety-related or other personality traits.

PMID- 12524161
TI  - Association study of the brain-derived neurotrophic factor (BDNF) gene with
      bipolar disorder.
AB  - Brain-derived neurotrophic factor (BDNF) belongs to a family of neurotrophic
      factors and has been demonstrated to promote the survival, differentiation, and
      maintenance of a broad variety of central nervous system neurons. Several reports
      have suggested that the BDNF gene is a plausible functional candidate gene
      underlying the predisposition for developing bipolar disorder (BPD). In the
      present study, we investigated the possible role of the BDNF gene in the etiology
      of BPD using a matched case-control association design in a Japanese population.
      There was no evidence for an allelic or genotypic association of two
      polymorphisms (-1360C>T and 196G>A) of the BDNF gene with BPD. Furthermore, no
      significant association was observed between these polymorphisms and either of
      two diagnostic subtypes (bipolars I and II disorder). The results suggest that
      the BDNF gene is unlikely to confer susceptibility to BPD.

PMID- 12524162
TI  - Asymmetrical enhancement of middle-latency auditory evoked fields with aging.
AB  - We studied the effects of aging on middle-latency auditory evoked fields (P50m),
      and analyzed their interhemispheric differences. Magnetic responses following
      tone-burst stimuli to the right ear were measured in groups of 11 younger and 15
      elderly subjects. The elderly subjects showed marked asymmetry in the P50m
      amplitudes. In the elderly group, the mean amplitude of the contralateral P50m
      was significantly larger (P<0.0005) than that of the ipsilateral P50m, while no
      asymmetry was shown in the younger group. The amplitude enlargement in the
      contralateral P50m showed significant correlation with age (R=0.60, P<0.005),
      while the ipsilateral P50m showed no correlation with age. These results suggest
      that the contralateral and ipsilateral auditory pathways are affected differently
      by ageing.

PMID- 12524163
TI  - Postural instability enhances motor responses to transcranial magnetic
      stimulation in humans.
AB  - Does the state of postural instability require a high hierarchical level of
      posture control? Electromyographic (EMG) activity of leg muscles was recorded
      during transcranial magnetic stimulation (TMS) of the motor cortex and electrical
      stimulation of the tibial nerve (H-reflex) in healthy subjects standing on a
      rigid floor and on a rocking platform. In the soleus muscle, TMS-evoked EMG
      responses increased considerably (2.2+/-1.1 times) when balancing on the rocking
      platform, whilst the H-reflex tended to decrease. The effect of support
      instability was specific to the muscles participating in the posture control. The
      results suggest that postural instability might change the state and the role of
      the motor cortex in equilibrium maintenance.

PMID- 12524164
TI  - Daily injections alter spine density in rat medial prefrontal cortex.
AB  - Apical dendrites of pyramidal neurons in medial prefrontal cortex are reorganized
      after chronic corticosterone treatment. In this study, we assessed the effects of
      chronic corticosterone administration on dendritic spines. Adult male rats
      received sc injections of either corticosterone or vehicle daily for 3 weeks or
      were left untreated. Layer II-III neurons in medial prefrontal cortex were
      stained using a Golgi-Cox procedure and spines were counted on the portions of
      apical dendrites where maximal corticosterone-induced dendritic changes occur. In
      vehicle- and corticosterone-treated rats, spine density proximal to the soma was
      increased relative to untreated rats, while spine density in the distal portion
      of the apical arbor was unchanged, suggesting that daily handling alone altered
      spine density. This stress-induced change in spine density likely reflects
      important functional changes in excitatory synaptic inputs in prefrontal cortex.

PMID- 12524165
TI  - Songorine, a diterpenoid alkaloid of the genus Aconitum, is a novel GABA(A)
      receptor antagonist in rat brain.
AB  - Songorine, a diterpenoid alkaloid isolated from the genus Aconitum, was recently
      found to enhance the excitatory synaptic transmission in rat hippocampus. The
      mechanism underlying the effects was examined in the present study. The alkaloid
      at 0.1-300 microM inhibited the specific binding of [(3)H]muscimol to Triton
      treated synaptic membranes of rat brain in a concentration-dependent manner
      (IC(50)=7.06 microM; 95% confidence limits: 3.28-10.84 microM). Scatchard
      analysis and Lineweaver-Burk double reciprocal plot of [(3)H]muscimol saturation
      binding data indicate a non-competitive inhibition of the alkaloid on the gamma
      aminobutyric acid(A) (GABA(A)) receptor. In acutely dissociated rat hippocampal
      neurons the alkaloid did not elicit current response, but markedly inhibited the
      GABA-induced inward current (IC(50)=19.6 microM). The results suggest that
      songorine is a novel non-competitive antagonist at the GABA(A) receptor in rat
      brain.

PMID- 12524166
TI  - Human acetylcholinesterase binds to mouse laminin-1 and human collagen IV by an
      electrostatic mechanism at the peripheral anionic site.
AB  - Acetylcholinesterase (EC 3.1.1.7; AChE) is known to induce neurite outgrowth and
      differentiation, but its ligands are as yet unknown. Laminin-1 and collagen IV
      were investigated as potential ligands for AChE. We observed specific saturable
      binding of biotinylated human AChE to mouse laminin and human collagen, with K(d)
      values of 4.9482 nM (SE 0.3145 nM) and 1.1617 nM (SE 0.1921 nM) respectively.
      Peripheral anionic site inhibitors (fasciculin, BW284c51, propidium and
      gallamine) also significantly reduced binding with fasciculin being the most
      effective. Significant reductions in AChE-laminin and AChE-collagen interactions
      were produced by a monoclonal anti-AChE antibody known to react with the
      peripheral anionic site, and a partial reduction with an antibody that partially
      recognises the site. Self-association of AChE was also observed (K(d)=16.3235 nM;
      SE 5.8120 nM); increasing markedly at low pH, but not significantly affected by
      either inhibitors or antibodies, suggesting a non-specific aggregation
      phenomenon. Binding to laminin and collagen was significantly reduced by
      increasing ionic strength and decreasing pH, indicating a dominant role for
      electrostatic interactions, and suggesting that the site may be different from
      the hydrophobic site identified for the AChE-amyloid interaction.

PMID- 12524167
TI  - Involvement of local anesthetic binding sites on IVS6 of sodium channels in fast
      and slow inactivation.
AB  - Local anesthetics (LAs) block Na(+) channels with a higher affinity for the fast
      or slow inactivated state of the channel. Their binding to the channel may
      stabilize fast inactivation or induce slow inactivation. We examined the role of
      the LA binding sites on domain IV, S6 (IVS6) of Na(+) channels in fast and slow
      inactivation by studying the gating properties of the mutants on IVS6 affecting
      LA binding. Mutation of the putative LA binding site, F1579C, inhibited fast and
      slow inactivation. Mutations of another putative LA binding site, Y1586C, and
      IVS6 residue involved in LA access and binding, I1575C, both enhanced fast and
      slow inactivation. None of the mutations affected channel activation. These
      results suggest that the LA binding site on IVS6 is involved in slow inactivation
      as well as fast inactivation, and these two gatings are coupled at the binding
      site.

PMID- 12524168
TI  - Photoresponse from the statocyst hair cell in Lymnaea stagnalis.
AB  - Sensory cells for associative learning of light and turbulence were studied in
      Lymnaea. Intracellular recordings with Lucifer Yellow filled electrodes were made
      from photoreceptors and statocyst hair cells. Photoreceptors had a long latency,
      graded depolarizing response to a flash of light; they extended their axon to the
      cerebral ganglion. The caudal hair cell, one of 12 cells in the statocyst,
      responded to brief light with a depolarization and superimposed impulse activity.
      It formed its terminal arborization close to the photoreceptor endings in the
      cerebral ganglion. Ca(2+)-free saline reversibly abolished the photoresponse in
      the hair cell, suggesting the information was conveyed via a chemical synapse.
      These findings demonstrated that sensory information for associative learning was
      convergent at the statocyst hair cell.

PMID- 12524169
TI  - Biphasic activation of apoptosis signal-regulating kinase 1-stress-activated
      protein kinase 1-c-Jun N-terminal protein kinase pathway is selectively mediated
      by Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors
      involving oxidative stress following brain ischemia in rat hippocampus.
AB  - Stress-activated protein kinase/extracellular signal-regulated kinase-1
      (SEK1/MKK4) was examined in a rat model of global brain ischemia. Western blot
      assay showed that SEK1 activation was biphasic in CA1 but not CA3/dentate gyrus.
      The second activation peak (3 days after ischemia) was prevented by pretreatment
      with l-naphthyl acetyl spermine (Naspm), a channel blocker of Ca(2+)-permeable
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, or N
      acetylcysteine (NAC), a free radical scavenger. Concomitantly, the late
      activation of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal
      protein kinase (JNK) was also prevented by Naspm or NAC. Moreover, phospho-SEK1
      and phospho-JNK co-immunoprecipitated with ASK1 and the bindings peaked at 3 days
      of reperfusion. Together with previous results, these findings indicate that
      Ca(2+)-permeable AMPA receptors are important routes to mediate the late
      activation of ASK1-SEK1-JNK pathway involving oxidative stress in hippocampal CA1
      region after ischemia.

PMID- 12524170
TI  - Vitamin E isoforms alpha-tocotrienol and gamma-tocopherol prevent cerebral
      infarction in mice.
AB  - Alpha-tocopherol and its derivatives have been shown to be effective in reducing
      cerebral ischemia-induced brain damage. However, the effects of other vitamin E
      isoforms have not been characterized. In the present study, we investigated the
      effects of six different isoforms of vitamin E on the ischemic brain damage in
      the mice middle cerebral artery (MCA) occlusion model. All vitamin E isoforms
      were injected i.v., twice, immediately before and 3 h after the occlusion. Alpha
      tocopherol (2 mM), alpha-tocotrienol (0.2 and 2 mM) and gamma-tocopherol (0.2 and
      2 mM) significantly decreased the size of the cerebral infarcts 1 day after the
      MCA occlusion, while gamma-tocotrienol, delta-tocopherol and delta-tocotrienol
      showed no effect on the cerebral infarcts. These results suggest that alpha
      tocotrienol and gamma-tocopherol are potent and effective agents for preventing
      cerebral infarction induced by MCA occlusion.

PMID- 12524171
TI  - Absence of association between an intercellular adhesion molecule 1 gene E469K
      polymorphism and Alzheimer's disease in Finnish patients.
AB  - Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein
      known to contribute to inflammatory responses, has been detected in the brain
      tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD
      or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis
      of these disorders. Our purpose was to investigate whether genetic variants of
      the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We
      genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control
      patients of Finnish origin. The distributions of the genotype and allele
      frequencies of the polymorphism did not differ significantly between the AD, PD
      or the control patients. We therefore conclude that the E469K polymorphism of
      ICAM1 is not a risk factor for AD or PD.

PMID- 12524172
TI  - Epidermal growth factor receptor expression is related to post-mitotic events in
      cerebellar development: regulation by thyroid hormone.
AB  - It has been established that thyroid hormone and neurotrophic factors both
      orchestrate developmental events in the brain. However, it is not clear how these
      two influences are related. In this study, we investigated the effects of thyroid
      hormone on cerebellar development and the coincident expression of transforming
      growth factor-alpha (TGF-alpha), a ligand in the epidermal growth factor (EGF)
      family, and the epidermal growth factor receptor (EGFR). Profiles of thyroid
      hormone expression were measured in postnatal animals and were found to peak at
      postnatal day 15 (P15). These levels dropped below detectable levels when mice
      were made hypothyroid with propylthiouracil (PTU). TGF-alpha and EGFR expression,
      as determined by RNAse protection assay, was maximal at P6 in normal animals, but
      remained low in hypothyroid animals, suggesting that thyroid hormone was
      responsible for their induction. In situ hybridization and immunohistochemical
      analysis of EGFR expression revealed that this receptor was present on granule
      cells within the inner zone of the external granule cell layer (EGL), suggesting
      that EGFR-ligands were not inducing granule cell proliferation. The persistence
      of EGFR expression on migrating granule cells and subsequent down-regulation of
      expression in the internal granule cell layer (IGL) implicates a role for EGFR
      ligands in differentiation and/or migration. In hypothyroid animals, we observed
      a delayed progression of granule cell migration, consistent with the persistence
      of EGFR labeling in the EGL, and in the 'pile-up' of labeled cells at the
      interface between the molecular layer and the Purkinje cell layer. Taken
      together, these results implicate thyroid hormone in the coordinated expression
      of TGF-alpha and EGFR, which are positioned to play a role in post-mitotic
      developmental events in the cerebellum.

PMID- 12524173
TI  - FGF-2, NGF and IGF-1, but not BDNF, utilize a nitric oxide pathway to signal
      neurotrophic and neuroprotective effects against alcohol toxicity in cerebellar
      granule cell cultures.
AB  - Neuronal death is a prominent neuropathological component of fetal alcohol
      syndrome (FAS). Identification of molecular agents and pathways that can
      ameliorate alcohol-induced cell loss offers possible therapeutic strategies for
      FAS and potential insight into its pathogenesis. This study investigated the
      effects of growth factors on cellular survival in alcohol-exposed cerebellar
      granule cell (CGC) cultures and examined the role of the nitric oxide (NO)-cGMP
      PKG (cGMP-dependent protein kinase) pathway in the cell survival-promoting
      effects of these growth factors. Primary CGC cultures were exposed to 0 or 400
      mg/dl ethanol, accompanied by either no growth factor or 30 ng/ml fibroblast
      growth factor-2 (FGF-2), nerve growth factor (NGF), insulin-like growth factor-1
      (IGF-1), brain-derived neurotrophic factor (BDNF) or epidermal growth factor
      (EGF). Viable neurons were quantified after 1 day of exposure. Two distinct types
      of cell survival-promoting effects of growth factors were detectable: (1) a
      neurotrophic effect, in which the growth factors diminished the background death
      of neurons that occurred in alcohol-free cultures; and (2) a neuroprotective
      effect, in which the growth factors diminished alcohol-induced cell death. The
      various growth factors differed markedly in their patterns of cell survival
      promotion. While BDNF and FGF-2 exerted both a neurotrophic and a neuroprotective
      effect, IGF-1 had only a neurotrophic effect and did not protect against alcohol
      toxicity, and NGF had only a neuroprotective effect and did not diminish
      background cell death. EGF had neither a neurotrophic nor a neuroprotective
      effect. In order to determine the role of the NO-cGMP-PKG pathway in the cell
      survival-promoting effects mediated by growth factors, cultures were exposed to
      one of several pharmacological inhibitors of the pathway, including NAME, LY83583
      and PKG inhibitor. The cell survival-promoting effects of FGF-2, NGF and IGF-1
      were all substantially reduced by each of the pathway inhibitors. In contrast,
      neither the neurotrophic nor the neuroprotective effects of BDNF were altered by
      any of the pathway inhibitors. Thus, growth factors differ in their patterns of
      neurotrophic and neuroprotective effects, and they differ in their reliance on
      the NO-cGMP-PKG pathway. While FGF-2, NGF and IGF-1 all signal their survival
      promoting effects through the NO-cGMP-PKG pathway, BDNF does not rely upon this
      pathway for signal transduction in CGC cultures.

PMID- 12524174
TI  - Ontogeny of choline acetyltransferase (ChAT) immunoreactivity in the brain of the
      urodele amphibian Pleurodeles waltl.
AB  - The ontogeny of cholinergic neurons has been studied in the brain of the urodele
      amphibian Pleurodeles waltl by means of choline acetyltransferase (ChAT)
      immunohistochemistry. Embryonic and larval stages were studied. The earliest ChAT
      immunoreactive (ChATi) cells were the primary motoneurons in the upper spinal
      cord, at embryonic stage 29. Slightly later, before hatching, the cranial nerve
      motor nuclei were immunopositive as well as non-motor populations in the
      developing inferior reticular nucleus, the nucleus of the solitary tract, the
      dorsal column nucleus and the retina. At initial larval stages, ChATi cells were
      located for the first time in the suprachiasmatic nucleus and the isthmic
      tegmentum. In addition, moderate immunoreactivity appeared in the Mauthner cells.
      During the period of active larval life the cholinergic systems maturated
      progressively and new ChATi cell groups were found in the caudal telencephalon
      and the habenula. Also extensive fiber labeling occurred at active larval stages.
      No transient ChAT expression was observed and even the Mauthner cells maintained
      their immunoreactivity after metamorphosis. A general caudorostral spatio
      temporal sequence of appearance of cholinergic structures was found in the brain.
      Comparison of the results observed in the urodele with previous data available
      only in amniotes shows numerous similarities and suggests a conservative
      developmental pattern of cholinergic systems in vertebrates.

PMID- 12524175
TI  - Implication of Trip15/CSN2 in early stage of neuronal differentiation of P19
      embryonal carcinoma cells.
AB  - Trip15/CSN2 is a transcriptional corepressor/a component of COP9 signalosome
      (CSN) and participates in various signaling pathways. However, participation of
      Trip15/CSN2 in neural differentiation is still obscure. Here, we show that
      Trip15/CSN2 plays a critical role in neuronal differentiation. The expression of
      Trip15/CSN2 mRNA was induced at an early stage of neuronal differentiation in the
      retinoic acid (RA)-treated P19 cells, but not in the triiodothyronine (T3)-primed
      cardiac muscular cell differentiation. The expression of Trip15/CSN2 mRNA in the
      rat brain was detected at E14 and the protein was localized in the nuclei of
      neonatal rat CNS neurons. Enforced expression of sense rat Trip15/CSN2 mRNA
      caused the downregulation of Oct-3/4 mRNA expression and was sufficient to
      convert P19 cells into neurons, but not glial cells, only after the aggregation
      without RA. In the presence of RA, exogenous expression of the sense mRNA caused
      the intense and rapid induction of neurogenic Brn-2 and Mash-1 mRNA expressions
      accompanying the strong downregulation of Oct-3/4 mRNA expression, and stimulated
      both neuronal and glial cell differentiations of P19 cells. In contrast, enforced
      expression of the antisense mRNA suppressed the commitment of RA-treated
      aggregation form of P19 cells to neuronal lineage. These data strongly suggest
      that Trip15/CSN2 could implicate in the commitment of multipotent embryonal
      carcinoma (EC) cells to neuronal fate through the downregulation of Oct-3/4 which
      suppresses neurogenic genes. Moreover, in addition to Trip15/CSN2, RA-regulated
      other factor(s) may be required for glial cell differentiation.

PMID- 12524176
TI  - Developmental changes in the effects of serotonin on neurons in the region of the
      pedunculopontine nucleus.
AB  - The percent of rapid eye movement (REM) sleep decreases dramatically between 10
      and 30 days postnatally in the rat. The pedunculopontine nucleus (PPN) is known
      to modulate waking and REM sleep. We recorded intracellularly from 127 neurons in
      the PPN in 12-21-day rat brainstem slices maintained in warmed, oxygenated
      artificial cerebrospinal fluid. We identified three types of PPN neurons based on
      intrinsic membrane properties, type I (LTS), type II (A) and type III (A+LTS), as
      previously described. The percent of type I neurons increased from 6% at 12 days
      to 17% by 21 days, while the percent of type III neurons decreased from 21% at 12
      17 days, to 4% after 17 days. Thus, PPN neurons may differentiate into type I
      bursting neurons and type II slow-firing neurons across this critical stage in
      development. The 5-HT1 receptor agonist 5-carboxyamido-tryptamine (5-CT) was
      found to hyperpolarize 58% of 12-16-day PPN neurons, did not affect 25% and
      depolarized 17%. However, a higher percentage of 17-21-day PPN neurons were
      hyperpolarized (85%), and a lower percentage unaffected (10%) or depolarized
      (5%), suggesting that serotonergic responses switched from both excitatory and
      inhibitory before, to almost purely inhibitory after, 17 days. These findings
      indicate a reorganization of PPN intrinsic membrane properties and serotonergic
      responses occur across this stage, in keeping with the proposed presence of a REM
      sleep inhibitory process during development. We suggest that disturbances in this
      developmental process may lead to disorders marked by increased REM sleep drive.

PMID- 12524177
TI  - Retinoic acid involvement in the reciprocal neurotrophic interactions between
      newt spinal cord and limb blastemas in vitro.
AB  - The purpose of this study was to investigate the reciprocal neurotrophic
      interaction between regenerating limb blastemas and spinal cord explants from the
      newt Notophthalmus viridescens. Axon outgrowth was measured from spinal cord
      explants in vitro to assess the neurotrophic activity of early to mid-bud stage
      blastemas after various treatments. When retinoic acid, a vitamin A metabolite,
      was added to the medium, it increased both the number and length of axons
      extending from spinal cord explants. Spinal cord explants co-cultured with
      blastemas that were previously treated with citral, an inhibitor of retinoic acid
      synthesis, extended significantly fewer axons than control co-cultures.
      Blastemas, which were denervated by surgical resection of the brachial plexus 48
      h before co-culture, also exhibited a significantly weaker neurotrophic activity
      than did control innervated blastemas. These results are consistent with a
      reciprocal interaction between blastema mesenchyme and nerves and suggest either
      a stimulatory or synergistic role for endogenous retinoic acid in the blastema
      derived trophic activity.

PMID- 12524178
TI  - Development of chick retina cells in culture: cobalt entry through AMPA receptors
      and expression of GluR4 AMPA receptor subunit.
AB  - The functionality of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)
      receptors in chick embryo retina cells during development in vitro was studied by
      using Co(2+) uptake, and these data were correlated with the expression of the
      AMPA receptor subunit GluR4. We found that at 5 h in vitro only a small number of
      cells took up Co(2+) upon stimulation with 100 microM kainate or other AMPA
      receptor agonists, in the presence of cyclothiazide (CTZ), to inhibit
      desensitisation. The number of cells sensitive to kainate increased from 5 h in
      vitro to 3 days in vitro (DIV), and remained relatively constant until 14 DIV.
      When the cells were stimulated with (2S,4S)-4-methylglutamic acid (30 microM), a
      specific kainate receptor agonist, after inhibiting desensitisation with
      concanavalin A, we did not observe an increase in the number of cells responding,
      as compared to the control. The expression of the AMPA receptor subunit GluR4
      during development was detected by immunofluorescence mainly at the perinuclear
      region of the cells, and the number of positive cells increased from 5 h in vitro
      to 7 DIV, and remained relatively constant until 14 DIV. The results suggest that
      AMPA receptors can be functionally active at early embryonic stages (5 h in
      vitro) in cultured retinal neurons, although in only a few cells, before synapse
      formation (E12). The localisation of GluR4 was well correlated with Co(2+) entry,
      since the strongest GluR4 immunoreactivity was found in the regions that showed
      the most intense labelling with Co(2+). Finally, we found that the expression
      levels of GluR4 at the neurites increased between 5 h in vitro and 7 DIV, near
      the period of synapse formation.

PMID- 12524179
TI  - Myelin transcription factor 1 (MyT1) immunoreactivity in infants with
      periventricular leukomalacia.
AB  - Myelin transcription factor 1 (MyT1) is a zinc-dependent, DNA-binding protein,
      and is known to be expressed in early progenitors of oligodendrocytes. We
      examined the immunoreactivity of MyT1 in developing human brains and brains with
      periventricular leukomalacia (PVL) to understand the relationship between the
      expression of MyT1 and myelination in PVL brains. MyT1-positive glial cells were
      first detected at 19 gestational weeks (GWs) and then gradually increased until
      26-29 GWs in the control group. Then they decreased and became very rare at 1
      year of age. The expression of MyT1 immunoreactivity shifted from the nucleus to
      the cytoplasm of the glial cells in the developmental time course. In the chronic
      stage of PVL, MyT1-positive cells were significantly increased around necrotic
      foci and some of the regions were coincident with increasing MBP and PLP
      immunoreactivity. These results may reflect myelin repair on dysmyelination
      around PVL areas. Therefore, MyT1 may play an important role in the myelin repair
      in PVL regions.

PMID- 12524180
TI  - The effects of combined fluid percussion traumatic brain injury and unilateral
      entorhinal deafferentation on the juvenile rat brain.
AB  - The current study was designed to address the effects of traumatic brain injury
      (TBI) on plasticity and reorganization in the juvenile brain. Given that two of
      the major pathological sequelae of TBI involve a generalized neuroexcitation
      insult and diffuse axonal injury, we have employed models of these pathologies,
      delivered either independently or in combination, to examine their effects on
      injury-induced synaptic reorganization of the dentate gyrus in the developing
      rat. Postnatal day 28 rats received either sham, central fluid percussion
      traumatic brain injury (TBI), unilateral entorhinal cortical lesion (UEC), or
      TBI+UEC (TUEC) injury. Cognitive performance was assessed in the Morris water
      maze (MWM) between 11 and 15 days post-injury and the brains were processed for
      synaptophysin immunohistochemistry and routine electron microscopy. The MWM
      results revealed that TBI or UEC lesions delivered independently do not produce
      significant morbidity in P28 rats. However, when these injuries are combined,
      they reveal significant deficits in the MWM, accompanied by measurable changes in
      the distribution of presynaptic synaptophysin immunoreactivity over the
      deafferented dentate molecular layer. These observations are further supported by
      qualitative ultrastructural alterations in synaptic architecture in the same
      subregions of the dentate neuropil. The present findings show that the resilience
      of the immature brain following TBI is reduced when neuroexcitatory insult is
      combined with deafferentation. Moreover, when deafferented tissue is assessed
      morphologically, evidence exists for aberrant plasticity and abnormal synaptic
      reorganization in the juvenile brain.

PMID- 12524181
TI  - Developmental increase of aspartoacylase in oligodendrocytes parallels CNS
      myelination.
AB  - Canavan disease, an autosomal-recessive neurogenetic disorder, is caused by
      mutations in aspartoacylase, an enzyme that deacetylates N-acetylaspartate to
      generate free acetate in the brain. Earlier studies have shown that
      aspartoacylase is primarily restricted to myelin synthesizing cells
      (oligodendroglia) in the CNS. These findings have led us to investigate the
      developmental expression of aspartoacylase gene in the rat brain in an attempt to
      shed more light on the role of this enzyme in myelination. In situ hybridization
      using a 35S riboprobe based on murine aspartoacylase cDNA was used in this study.
      The probe hybridized mostly to the white matter tracts with different densities
      depending on the age of the animal and region of the brain examined. Little or no
      hybridization signals were detected in the 1-day-old rats, whereas the signal was
      clearly detectable in most of the white matter regions of the CNS in the 11-day
      old rats. The signal density markedly increased at postnatal day 17, the peak of
      myelination. Thereafter, the hybridization signals decreased somewhat but still
      could be observed in the adult animals. Thus, the developmental expression
      pattern of aspartoacylase gene in the postnatal brain closely parallels
      myelination in the CNS. In the CNS, the hybridization signal of ASPA appeared to
      be restricted primarily to oligodendrocytes, the primary myelin synthesizing cell
      type in the CNS. However, the signal was not detectable in rat sciatic nerve
      (Schwann cells) of the peripheral nervous system. These findings indicate that
      the role of N-acetylaspartate in myelin synthesis is restricted to the CNS.
      Furthermore, they provide additional support for the acetate deficiency
      hypothesis of Canavan disease and also make a stronger case for acetate
      supplementation as an immediate and inexpensive therapy for Canavan disease.

PMID- 12524183
TI  - Rat nerve regeneration through a silicone chamber implanted with negative carbon
      ions.
AB  - We investigated whether a tube with its inner surface implanted with negatively
      charged carbon ions (C(-) ions) would enable axons to extend over a distance
      greater than 10 mm. The tube was found to support nerves regenerating across a 15
      mm-long inter-stump gap. Silicone treated with C(-) ions showed increased
      hydrophilic properties and cellular affinity, and axon regeneration was promoted
      with this increased biocompatibility.

PMID- 12524182
TI  - Alterations in PKCgamma in the mouse hippocampus after prenatal exposure to
      heroin: a link from cell signaling to behavioral outcome.
AB  - Administration of heroin to pregnant mice evokes neurochemical and behavioral
      deficits consequent to disruption of septohippocampal cholinergic innervation,
      notably involving desensitization of the ability of cholinergic receptors to
      activate PKC activity. The present study further evaluates whether
      desensitization occurs specifically for the PKCgamma isoform, the behaviorally
      relevant subtype, as compared to PKCalpha. Mice were exposed transplacentally to
      heroin on gestational days (GD) 9-18 via s.c. maternal injections (10 mg/kg per
      day). In young adulthood (50 days old), control offspring showed an increase in
      hippocampal cell membrane PKCgamma after incubation with the muscarinic
      cholinergic receptor agonist, carbachol, indicative of translocation from the
      cytosol. Prenatal exposure to heroin eliminated this response, whereas basal
      PKCgamma levels were unchanged. In contrast, PKCalpha, which is not related to
      heroin-induced behavioral deficits, did not show a loss of response. The present
      findings strongly point to abnormalities in the responsiveness of PKCgamma as a
      mechanism underlying the neurobehavioral teratogenicity of heroin.

PMID- 12524184
TI  - Development of the mouse vestibular system in the absence of gravity perception.
AB  - The tilted mutant mouse, which lacks otoconia in the inner ear, was used to study
      development of the mouse vestibular system in the absence of gravity perception.
      Otoconia are dense particles composed of proteins and calcium carbonate crystals
      suspended in the gelatinous macular membrane. They enhance, and are largely
      responsible for, sensitivity to gravity. Morphometric analysis of the vestibular
      ganglion showed that the mutant developed more slowly than the normal controls,
      both in rate of development and cell number, particularly during the first week
      of post-natal development. The mutant ganglia also exhibited a reduction of cells
      during the first 6 days of post-natal development.

PMID- 12524185
TI  - Anatomy of neurogenesis in the early zebrafish brain.
AB  - The detailed architecture of postembryonic (i.e. secondary, as opposed to
      primary) neurogenesis in the zebrafish brain at 2 days postfertilization was
      investigated by studying expression domains of various proneural basic helix-loop
      helix genes (i.e. neuroD=nrd, neurogenin1=ngn1, Zash-1b) and neurogenic genes
      (i.e. Notch-1a, deltaA) on the level of in situ-hybridized sectioned material and
      compared with brain sections of the same age immunostained for PCNA (a
      proliferation marker) or for Hu-proteins (marker for early neuronal
      differentiation). Whereas both Notch-1a and deltaA domains are present in all
      proliferative zones of the brain, only the more diffuse and scattered deltaA
      expression appears to extend additionally into the adjacent postmitotic gray
      matter. Zash-1b is the first achaete-scute orthologue shown here to be expressed
      exclusively in all proliferative central nervous zones (except for the eye). The
      ngn1 and nrd genes are typically both expressed in overlapping fashion in many
      but not all-brain regions, with ngn1 being more restricted towards the
      ventricular proliferative zones and nrd extending more laterally. This fact as
      well as comparisons with PCNA- and Hu-immunostains indicate that a great
      proportion of ngn1-positive cells are mitotic, but some appear to extend into the
      postmitotic gray matter where the nrd-domains lie. A comparison of the relative
      extents of PCNA- (proliferative), nrd- (freshly determined) and Hu-positive
      (differentiating) cell populations allows to determine the relative maturation
      state of a given brain part. Similar to findings in late embryonic amniote
      brains, expression of nrd is absent (from 2 to 5 days) in the zebrafish
      subpallium, ventral preoptic region, ventral thalamus and hypothalamus. These
      four regions are also free of ngn1 expression (with the exception of an unusual
      peripheral ngn1 domain in the preoptic region), indicating that a neurogenetic
      network not involving nrd and ngn1 is at work there. Our characterization of
      locally distinct patterns and dynamics of secondary neurogenesis in the entire
      early (2 dpf) postembryonic zebrafish brain delivers the blueprint for more
      specialized functional studies.

PMID- 12524186
TI  - Imaging of fullerene-like structures in CNx thin films by electron microscopy;
      sample preparation artefacts due to ion-beam milling.
AB  - The microstructure of CN(x) thin films, deposited by reactive magnetron
      sputtering, was investigated by transmission electron microscopy (TEM) at 200kV
      in plan-view and cross-sectional samples. Imaging artefacts arise in high
      resolution TEM due to overlap of nm-sized fullerene-like features for specimen
      thickness above 5nm. The thinnest and apparently artefact-free areas were
      obtained at the fracture edges of plan-view specimens floated-off from NaCl
      substrates. Cross-sectional samples were prepared by ion-beam milling at low
      energy to minimize sample preparation artefacts. The depth of the ion-bombardment
      induced surface amorphization was determined by TEM cross sections of ion-milled
      fullerene-like CN(x) surfaces. The thickness of the damaged surface layer at 5
      degrees grazing incidence was 13 and 10nm at 3 and 0.8keV, respectively, which is
      approximately three times larger than that observed on Si prepared under the same
      conditions. The shallowest damage depth, observed for 0.25keV, was less than 1nm.
      Chemical changes due to N loss and graphitization were also observed by X-ray
      photoelectron spectroscopy. As a consequence of chemical effects, sputtering
      rates of CN(x) films were similar to that of Si, which enables relatively fast
      ion-milling procedure compared to carbon compounds. No electron beam damage of
      fullerene-like CN(x) was observed at 200kV.

PMID- 12524187
TI  - Atomically resolved field emission patterns of single-walled carbon nanotubes.
AB  - The electron emission and structural properties of single-walled carbon nanotubes
      (SWCNTs) were investigated by using field emission microscopy (FEM). The
      transmission electron microscopy micrograph confirmed the existence of an SWCNT
      bundle on the W tip. Under appropriate experimental conditions, an FEM image with
      an elliptic ring-like structure composed of separated bright dots was obtained, a
      reasonable interpretation of it is that it was produced from the open end for a
      zigzag (16,0) SWCNT protruding from the SWCNT bundle, each bright dot
      corresponding to a single atom at the open end. And, if true, this means that the
      FEM demonstrated 0.2nm resolution, which was theoretically possible for the
      assumed geometry. The calculated value of the magnification of the pattern was
      also consistent with the measured value if the value of the compression factor
      beta was set at 1.76.

PMID- 12524188
TI  - Preparation of flat carbon support films.
AB  - Wrinkling of carbon support films is known to limit the resolution of electron
      microscopy images of protein two-dimensional crystals. The origin of carbon
      wrinkling during preparation of the support films was investigated by reflected
      light microscopy. We observed that carbon films go through several states during
      their preparation. While dried carbon films have a tendency to be wrinkled, a
      flat state is observed transiently before complete drying. This state could be
      stabilized by the addition of sugars or tannic acid to the embedding medium. An
      alternative method for preparing flat carbon films was developed, in which a
      sandwich is formed by two symmetrical carbon films positioned on both sides of a
      grid. The formation of sandwiched carbon films was facilitated by the use of
      grids with thin bars. The carbon sandwich films were flat, stable, and easily and
      reproducibly prepared.

PMID- 12524189
TI  - Development of a specimen holder for in situ generation of pure in-plane magnetic
      fields in a transmission electron microscope.
AB  - As the development of quantised storage media progresses, detailed knowledge is
      required about the magnetisation reversal behaviour of sub-micron sized magnetic
      structures in external magnetic fields. Using the Lorentz mode of transmission
      electron microscopy (LTEM) the magnetic microstructure of thin film samples can
      be imaged with high spatial resolution. A novel approach for in situ magnetising
      experiments is described which combines the development of a custom-made sample
      holder which generates two orthogonal in-plane components of magnetic field in
      the specimen plane with the benefit of computer-controlled variation of the
      field. We present a specimen stage suitable for a Philips CM30 Twin/LTEM, which
      allows the generation of well-defined magnetic in-plane fields in the TEM.

PMID- 12524190
TI  - Improving the analysis of small precipitates in HSLA steels using a plasma
      cleaner and ELNES.
AB  - The change from producing high strength low alloy (HSLA) steel sheet by
      conventional thick slab casting to producing it by direct charged thin slab
      casting causes a major change in the evolution of the precipitation. A key area
      of interest is the composition of the sub-10nm precipitates used to produce
      dispersion hardening. Carbon extraction replicas are frequently used to study
      precipitates in steels and other metals. When used with annular dark field
      imaging, this technique gives high contrast images of the precipitates while the
      thin carbon film adds little background or additional characteristic signals to
      either electron energy loss spectra or energy dispersive X-ray spectra. The
      method has the additional major advantage of removing the ferromagnetic matrix
      when studying HSLA steels. However, when the precipitates contain carbon, the C K
      edge is dominated by the contribution from the amorphous carbon film. A plasma
      cleaner can be used to thin this carbon film to approximately 0.5 nm or less and
      then the contribution from the carbon in the precipitate can be separated from
      that in the carbon film using the electron energy loss near edge structure. A
      similar approach can be taken to separate the oxygen content of the precipitate
      from that of oxides formed from low-level impurities in the amorphous carbon
      during the plasma thinning process. In most cases, the precipitate studied here
      contained little or no oxygen even for the smallest sizes examined (approximately
      4 nm). The precipitates contain mainly nitrogen with little carbon. For some
      compositions, the precipitates are clearly sub-stoichiometric.

PMID- 12524191
TI  - A novel STM-assisted microwave microscope with capacitance and loss imaging
      capability.
AB  - We report a new technique of scanning capacitance microscopy at microwave
      frequencies. A near field scanning microwave microscope probe is kept at a
      constant height of about 1 nm above the sample with the help of scanning
      tunneling microscope (STM) feedback. The microwaves are incident onto the sample
      through a coaxial resonator that is terminated at one end with a sharp tip (the
      same tip is used to conduct STM), and capacitively coupled to a feedback circuit
      and microwave source at the other end. The feedback circuit keeps the source
      locked onto the resonance frequency of the resonator and outputs the frequency
      shift and quality factor change due to property variations of the sample. The
      spatial resolution due to capacitance variations is congruent with 2.5 nm. The
      microwave microscope is sensitive to sample sheet resistance, as demonstrated
      through measurements on a doped silicon sample. We develop a quantitative
      transmission line model treating the tip to sample interaction as a series
      combination of capacitance and sheet resistance in the sample.

PMID- 12524193
TI  - Particle finding in electron micrographs using a fast local correlation
      algorithm.
AB  - A versatile tool for selecting particles from electron micrographs, intended for
      single particle analysis and three-dimensional reconstruction, is presented. It
      is based on a local real-space correlation method. Real-space correlations
      calculated over a local area are suitable for finding small objects or patterns
      in a larger field. They provide a very sensitive measure-of-fit, partly due to
      local optimisation of the numerical scaling. It is equivalent to least squares
      with optimised scaling between the two objects being correlated. The only
      disadvantage of real-space methods is that they are slow to compute. A fast local
      correlation algorithm based on Fourier transforms has been developed, which is
      approximately two orders of magnitude faster than the explicit real-space
      formulation. The algorithm is demonstrated by application to the problem of
      locating images of macromolecules in transmission electron micrographs of
      unstained frozen hydrated specimens. This is a challenging computational problem
      because these images have low contrast and a low signal-to-noise ratio. Picking
      particles by hand is very time consuming and can be less accurate. The automated
      procedure gives a significant increase in speed, which is important if large
      numbers of particles have to be picked.

PMID- 12524192
TI  - Atomic force microscopy study of chromosome surface structure changed by protein
      extraction.
AB  - We applied atomic force microscopy (AFM) to investigate the surface structure of
      barley chromosome in combination with a chemical treatment method. As a result,
      we have obtained high-resolution topographic images of granular structures with a
      diameter of ca. 50 nm on the surface of critical-point dried metaphase
      chromosomes. Treatment with 2M NaCl significantly modified the chromosome surface
      structure: surface roughness was increased and chromosome thickness was
      decreased. The NaCl treatment extracted two major proteins with molecular weights
      of 4000 and 20,000 Da. These proteins might be belonging to non-histone protein
      families that do not contain any aromatic amino acid. The results demonstrate the
      advantage of the combined method of high-resolution AFM imaging and chemical
      treatments for understanding nano-scale surface structures of the chromosome.

PMID- 12524194
TI  - Apertureless near-field scanning Raman microscopy using reflection scattering
      geometry.
AB  - The combination of near-field scanning optical microscopy and Raman spectroscopy
      provides chemical/structural specific information with nanometer spatial
      resolution, which are critically important for a wide range of applications,
      including the study of Si devices, nanodevices, quantum dots, single molecules of
      biological samples. In this paper, we describe our near-field Raman study using
      apertureless probes. Our system has two important features, critical to practical
      applications. (1) The near-field Raman enhancement was achieved by Ag coating of
      the metal probes, without any preparation of the sample, and (2) while all other
      apertureless near-field Raman systems were constructed in transmission mode, our
      system works in the reflection mode, making near-field Raman study a reality for
      any samples. We have obtained the first 1D Raman mapping of a real Si device with
      1s exposure time. This is a very significant development in near-field scanning
      Raman microscopy as it is the first demonstration that this technique can be used
      for imaging purpose because of the short integration time. In addition, the metal
      tips used in our set-up can be utilized to make simultaneous AFM and electrical
      mappings such as resistance and capacitance that are critical parameters for
      device applications.

PMID- 12524195
TI  - Lattice parameters from direct-space images at two tilts.
AB  - Lattices in three dimensions are oft studied from the "reciprocal space"
      perspective of diffraction. Today, the full lattice of a crystal can often be
      inferred from direct-space information about three sets of non-parallel lattice
      planes. Such data can come from electron-phase (or less easily Z contrast images)
      taken at two tilts, provided that one image shows two non-parallel lattice
      periodicities, and the other shows a periodicity not coplanar with the first two.
      We outline here protocols for measuring the 3D parameters of cubic lattice types
      in this way. For randomly oriented nano-crystals with cell side greater than
      twice the continuous transfer limit, orthogonal +/-15 degrees and +/-10 degrees
      tilt ranges might allow one to measure 3D parameters of all such lattice types in
      a specimen from only two well-chosen images. The strategy is illustrated by
      measuring the lattice parameters of a 10nm WC(1-x) crystal in a plasma-enhanced
      chemical-vapor deposited thin film.

PMID- 12524196
TI  - Evaluation of a hybrid pixel detector for electron microscopy.
AB  - We describe the application of a silicon hybrid pixel detector, containing 64 by
      64 pixels, each 170 microm(2), in electron microscopy. The device offers improved
      resolution compared to CCDs along with faster and noiseless readout. Evaluation
      of the detector, carried out on a 120 kV electron microscope, demonstrates the
      potential of the device.

PMID- 12524197
TI  - Holographic voltage profiling on 75 nm gate architecture CMOS devices.
AB  - Voltage profiles of the source-drain region of a CMOS transistor with 75nm gate
      architecture taken from an off-the-shelf Intel PIII processor are presented. The
      sample preparation using a dual beam system is discussed as well as details of
      the electron optical setup of the microscope. Special attention is given to the
      analysis of the reconstructed holograms.

PMID- 12524198
TI  - Application of evanescent wave optics to the determination of absolute distance
      in surface force measurements using the atomic force microscope.
AB  - A combined scanning near field optical/atomic force microscope (AFM) is used to
      obtain surface force measurements between a near field sensing tip and a tapered
      optical fibre surface, whilst simultaneously detecting the intensity of the
      evanescent field emanating from the fibre. The tapered optical fibre acts as a
      compliant sample to demonstrate the possible use of the near field intensity
      measurement system in determining 'real' surface separations from normal AFM
      surface force measurements at sub-nanometer resolution between deformable
      surfaces.

PMID- 12524199
TI  - Improved comparison of low energy loss spectra with band structure calculations:
      the example of BN filaments.
AB  - Electron energy loss spectra have been recorded from BN filaments for energy
      losses between 2 and 50eV. They compare well with other BN shapes (nanotubes,
      sheets, etc). The interpretation of all the peaks in the spectra has been made
      via an ab initio calculation using the FLAPW code WIEN97 (A full potential
      linearized augmened plane wave package for calculating crystal properties,
      Karlheinz Schwarz, Techn. Universitat Wien, Austria, 1999. ISBN 3-9501031-0-4).
      In order to fully simulate the observed spectra, the geometry particular to the
      EELS experiment has been taken into account making use of Wessjohann's
      relativistic formula for thin anisotropic slabs (Phys. Stat. Sol. B 77 (1976)
      535). Furthermore, the effect of the convergent beam has been introduced into the
      simulation and has been proven to be an important parameter in obtaining the
      corresponding peak intensities.

PMID- 12524200
TI  - Deconvolution of electron diffraction patterns of amorphous materials formed with
      convergent beam.
AB  - To perform reduced density function (G(r)) analysis on electron diffraction
      patterns of amorphous materials formed with convergent beams, the effects of
      convergence must be removed from the diffraction data. Assuming electrons
      incident upon the sample in different directions are incoherent, this can be done
      using deconvolution (Ultramicroscopy 76 (1999) 115). In this letter we show that
      the combination of an energy filtering transmission electron microscope with an
      image plate, increases the accuracy with which diffraction data can be measured
      and, subsequently, the accuracy of the deconvolution.

PMID- 12524201
TI  - Limitations on the s-state approach to the interpretation of sub-angstrom
      resolution electron microscope images and microanalysis.
AB  - The s-state approach is useful for analysing transmission electron microscope
      images of a thin crystalline foil consisting of well-separated atomic columns. It
      assumes that the signal collected (e.g., the annular dark-field image, the EELS
      spectrum) can be attributed to only the lowest-energy bound eigenstate of the two
      dimensional projected potential of a single column. When, however, columns are
      close, the form of the bound states depends on more than one column, which
      implies that interpretation of the signal may not be so simple. For closely
      spaced columns we show that the simple s-state approach fails for the case of a
      sub-Angstrom probe initially centred on one column of a pair, because two bound
      states are excited. The energy in the probe is almost completely transferred to
      the neighbouring column after it has propagated some tens of nanometres through
      the foil and then is transferred back. Signals which relate directly to the local
      probe intensity (e.g. annular dark-field formed by thermal diffuse scattering,
      EELS) must be analysed in terms of the two bound states. Accurate calculations of
      bound states of pairs of columns are more demanding than for a single column but
      sufficient accuracy can be achieved from knowledge of the 1s-states of isolated
      columns. We provide formulae for the bound states of a column pair. These can be
      used to determine if image analysis requires the extension to the s-state
      approach described in this paper.

PMID- 12524203
TI  - Nanoparticle-mediated gene delivery to tumour neovasculature.
AB  - The alpha(v)beta(3) integrin is a potential pharmacological target for anti
      angiogenic therapy. A recent report describes the use of alpha(v)beta(3)-targeted
      nanoparticles to deliver a gene to tumour vasculature selectively. This resulted
      in substantial tumour regression in several experimental mouse tumour models.
      Hence, this approach has great potential for the treatment of human cancer.

PMID- 12524204
TI  - Classifying human cancer by analysis of gene expression.
AB  - With the development and application of DNA microarrays, the expression of almost
      all human genes can now be systematically examined in human malignancies. This
      can lead to the identification of candidate molecular targets for therapeutic
      intervention and biomarkers for early detection of these diseases. However,
      perhaps the most exciting result to come from this research has been the
      demonstration that patterns of gene expression can distinguish between tumors of
      different anatomical origin, and define new subgroups of cancer with similar
      histological appearance, but distinct molecular profiles. Some of these new
      molecular subclasses of tumor appear to correlate with clinical behavior. If
      substantiated in larger studies, this might form a basis for stratifying patients
      so that they receive optimal therapeutic treatment and follow-up.

PMID- 12524205
TI  - Cancer prevention -- the potential for diet to modulate molecular signalling.
AB  - As our understanding of the development of cancer and the complex signalling
      mechanisms involved improves, we are beginning to appreciate the enormous
      potential for intervention strategies that prevent or slow down the disease
      process. Although much research is currently aimed at developing drugs to target
      key molecules in tumour cells that are responsible for their proliferation and
      survival, dietary constituents also have potential as anti-cancer agents. Our
      goal should be not only to identify carcinogenic changes as early as possible and
      to intervene effectively long before life-threatening tumours develop, but also
      to understand how a balanced, healthy diet can contribute to reduced incidence,
      as epidemiology so tantalizingly suggests.

PMID- 12524206
TI  - Mouse models of neurofibromatosis type I: bridging the GAP.
AB  - Neurofibromatosis type I (NF1) is an autosomal dominant disorder caused by
      mutations in the NF1 gene, leading to a variety of abnormalities in cell growth
      and differentiation, and to learning disabilities. The protein encoded by NF1,
      neurofibromin, has several biochemical functions and is expressed in a variety of
      different cell populations. Hence, determination of the molecular and cellular
      mechanisms that underlie the different NF1 symptoms is difficult. However,
      studies using mouse models of NF1 are beginning to unravel the mechanisms that
      underlie the various symptoms associated with the disease. This knowledge will
      aid the development of treatments for the different pathological processes
      associated with NF1.

PMID- 12524207
TI  - Resistance in the anti-angiogenic era: nay-saying or a word of caution?
AB  - The hope that anti-angiogenic therapy might be the panacea for cancer has not yet
      been realized. There are many possible reasons for this, including endothelial
      and tumor cell heterogeneity, the presence of survival factors within the tumor
      micro-environment, the problem of defining the best dose and schedule for anti
      angiogenic therapies, and angiogenesis-independent regrowth of tumors. Once these
      problems are understood, we can begin to evaluate approaches to thwarting them.
      These could include combining anti-angiogenic therapies with chemotherapy, with
      other anti-angiogenic agents or with other biological therapies. Another approach
      would be to employ a particular agent or combination of agents that target
      processes crucial to the survival of a particular cancer.

PMID- 12524208
TI  - Notch, a unifying target in T-cell acute lymphoblastic leukemia?
AB  - The expression of both Notch3 and pre-T-cell-receptor (pre-TCR) invariant chain
      appears to be a common feature of all T-cell acute lymphoblastic leukemias (T
      ALL). Notch genes, and other genes that are dysregulated in some T-ALL subgroups,
      encode factors that play a crucial role in both T-cell development and
      leukemogenesis. A complex network of signals, involving Notchs, pre-TCR, nuclear
      factor kappaB and E2A, appears to be responsible for the leukemogenesis process.
      Thus, T-ALL is a paradigm for developmental pathways that underlie the
      pathogenesis of this disease.

PMID- 12524209
TI  - Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4.
AB  - There are still many unanswered questions regarding the processes by which
      extracellular signals are transduced from plasma-membrane receptors to the
      transcription machinery in the nucleus and the translation machinery in the
      cytoplasm. Some of these gene expression events become misregulated as a result
      of environmental or endogenous exposure to agents that cause multistage
      carcinogenesis. We are now beginning to identify and validate the crucial
      molecular events that drive the rate-limiting steps of carcinogenesis and to
      target these events for cancer prevention. Transcription factors AP-1 and nuclear
      factor kappa B can be specifically targeted to prevent cancer induction in mouse
      models. A protein known as programmed-cell-death-4 is a new potential molecular
      target that has a surprising mode of action.

PMID- 12524211
TI  - Environmental health science and the legacy of popular literature.

PMID- 12524210
TI  - Priorities for development of research methods in occupational cancer.
AB  - Occupational cancer research methods was identified in 1996 as 1 of 21 priority
      research areas in the National Occupational Research Agenda (NORA). To implement
      NORA, teams of experts from various sectors were formed and given the charge to
      further define research needs and develop strategies to enhance or augment
      research in each priority area. This article is a product of that process. Focus
      on occupational cancer research methods is important both because occupational
      factors play a significant role in a number of cancers, resulting in significant
      morbidity and mortality, and also because occupational cohorts (because of higher
      exposure levels) often provide unique opportunities to evaluate health effects of
      environmental toxicants and understand the carcinogenic process in humans.
      Despite an explosion of new methods for cancer research in general, these have
      not been widely applied to occupational cancer research. In this article we
      identify needs and gaps in occupational cancer research methods in four broad
      areas: identification of occupational carcinogens, design of epidemiologic
      studies, risk assessment, and primary and secondary prevention. Progress in
      occupational cancer will require interdisciplinary research involving
      epidemiologists, industrial hygienists, toxicologists, and molecular biologists.

PMID- 12524212
TI  - Protein disulfide bond formation in prokaryotes.
AB  - Disulfide bonds formed between pairs of cysteines are important features of the
      structure of many proteins. Elaborate electron transfer pathways have evolved
      Escherichia coli to promote the formation of these covalent bonds and to ensure
      that the correct pairs of cysteines are joined in the final folded protein. These
      transfers of electrons consist, in the main, of cascades of disulfide bond
      formation or reduction steps between a series of proteins (DsbA, DsbB, DsbC, and
      DsbD). A surprising variety of mechanisms and protein structures are involved in
      carrying out these steps.

PMID- 12524213
TI  - Aliphatic epoxide carboxylation.
AB  - Aliphatic epoxides (epoxyalkanes) are highly reactive electrophilic molecules
      that are formed from the monooxygenase-catalyzed epoxidation of aliphatic
      alkenes. The bacterial metabolism of short-chain epoxyalkanes occurs by a three
      step pathway resulting in net carboxylation to beta-ketoacids. This pathway uses
      the atypical cofactor coenzyme M (CoM; 2-mercaptoethanesulfonic acid) as the
      nucleophile for the epoxide ring opening and as the carrier of 2-hydroxyalkyl-
      and 2-ketoalkyl-CoM intermediates. Four enzymes are involved in epoxide
      carboxylation: a zinc-dependent alkyltransferase, two short-chain dehydrogenases
      with specificities for the chiral products of the R- and S-1,2-epoxyalkane ring
      opening, and an NADPH:disulfide oxidoreductase/carboxylase that reduces the
      thioether bond of the 2-ketoalkyl-CoM conjugate and carboxylates the resulting
      carbanion. In this review, we summarize the biochemical, mechanistic, and
      structural features of the enzymes of epoxide carboxylation and show how these
      enzymes, together with CoM, work in concert to achieve this highly unusual
      carboxylation reaction.

PMID- 12524215
TI  - Adverse effects of supplemental L-arginine in atherosclerosis: consequences of
      methylation stress in a complex catabolism?

PMID- 12524216
TI  - Thrombospondins and premature coronary artery disease: time to go beyond genotype
      phenotype association studies.

PMID- 12524217
TI  - Mechanism of action of high-dose factor VIIa: points of agreement and
      disagreement.

PMID- 12524219
TI  - Hormone replacement therapy and risk of cardiovascular disease: implications of
      the results of the Women's Health Initiative.
AB  - The higher rates of coronary heart disease (CHD), stroke, and venous thrombosis
      among women taking estrogen and progesterone (E+P) compared with placebo in the
      Women's Health Initiative clinical trial have important implications for women's
      health. Previous studies in both men and women have shown that estrogen therapy
      lowers low-density lipoprotein cholesterol and raises high-density lipoprotein
      cholesterol. The changes in these lipoproteins should be associated with at least
      a 30% decline in CHD risk. Estrogens increased very-low-density lipoprotein
      (VLDL) triglyceride levels and C-reactive protein. There is evidence that
      estrogens increase thrombin generation and fibrinolysis. The increase in VLDL
      triglycerides may enhance thrombotic risk as well as higher levels of atherogenic
      lipoproteins, such as dense low-density lipoprotein. Genetic variations in
      estrogen receptors and thrombosis or fibrinolysis may also be important in risks
      associated with E+P therapy. The increased risk of CHD and stroke with E+P
      therapy may be attributable to rise in VLDL triglycerides and thrombosis.

PMID- 12524220
TI  - The dynamics of thrombin formation.
AB  - The central event of the hemostatic process is the generation of thrombin through
      the tissue factor pathway. This is a highly regulated, dynamic process in which
      thrombin itself plays many roles, positively and negatively its production and
      destruction. The hemostatic process is essential to normal physiology and is also
      the Achilles heel of our aging population. The inappropriate generation of
      thrombin may lead to vascular occlusion with the consequence of myocardial
      infarction, stroke, pulmonary embolism, or venous thrombosis. In this review, we
      summarize our present views regarding the tissue factor pathway by which thrombin
      is generated and the roles played by extrinsic and intrinsic factor Xa generating
      complexes in hemostasis and the roles of the stoichiometric and dynamic
      inhibitors that regulate thrombin generation.

PMID- 12524221
TI  - Functional interplay between angiotensin II and nitric oxide: cyclic GMP as a key
      mediator.
AB  - Angiotensin II (Ang II) and nitric oxide (NO) signaling pathways mutually
      regulate each other by multiple mechanisms. Ang II regulates the expression of NO
      synthase and NO production, whereas NO downregulates the Ang II type I (AT1)
      receptor. In addition, downstream effectors of Ang II and NO signaling pathways
      also interact with each other. A feedback mechanism between Ang II and NO is
      critical for normal vascular structure and function. Imbalance of Ang II and NO
      has been implicated in the pathophysiology of many vascular diseases. In this
      review, we focus on the diverse ways in which Ang II and NO interact and the
      importance of the balance between the signaling pathways activated by these
      mediators.

PMID- 12524222
TI  - Estrogen reduces angiotensin II-induced nitric oxide synthase and NAD(P)H oxidase
      expression in endothelial cells.
AB  - OBJECTIVE: Angiotensin II (AII) has been shown to increase endothelial NAD(P)H
      oxidase activity, which is a source of superoxide anion that in turn may induce
      the formation of peroxynitrite. Estrogen (E2) has been reported to have vascular
      protective effects. In this study, we hypothesized that E2 reduces the AII
      induced expression of NAD(P)H oxidase and peroxynitrite in endothelial cells.
      METHODS AND RESULTS: Endothelial cells were cultured and stimulated with AII in
      the absence or presence of E2. Western blots were used to assess nitric oxide
      synthase (NOS) and NAD(P)H oxidase expression. Immunofluorescence of
      nitrotyrosine provided evidence of peroxynitrite formation. Our data indicate
      that AII increased the expression of endothelial NOS, inducible NOS, and NAD(P)H
      oxidase in a dose-dependent manner, which was attenuated by incubation with
      either E2, superoxide dismutase, or the AII type 1 receptor (AT1R) inhibitor
      candesartan. Estrogen as well as superoxide dismutase also inhibited AII-induced
      AT(1)R expression and nitrotyrosine staining. The effects of E2 on the AII
      responses were not inhibited by the E2 receptor antagonist ICI-182,780.
      CONCLUSIONS: AII stimulation of endothelial cells increases expression of NAD(P)H
      oxidase and NOS, which may contribute to oxidative stress, as evidenced by
      peroxynitrite formation. E2 inhibits these AII effects, possibly through reduced
      AT1R expression.

PMID- 12524223
TI  - Effect of peroxisome proliferator-activated receptor-alpha and -gamma activators
      on vascular remodeling in endothelin-dependent hypertension.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptors (PPARs) may modulate in
      vitro the vascular production of vasoactive peptides such as endothelin-1 (ET-1).
      Thus, we investigated in vivo the interaction between PPARs and ET-1 in
      deoxycorticosterone acetate (DOCA)-salt rats that overexpress vascular ET-1.
      METHODS AND RESULTS: Unilaterally nephrectomized 16-week-old Sprague-Dawley rats
      (Uni-Nx) were divided into 4 groups (n=6 each): control group, DOCA-salt group,
      DOCA-salt+PPAR-gamma activator (rosiglitazone, 5 mg x kg(-1) x d(-1)), or DOCA
      salt+PPAR-alpha activator (fenofibrate, 100 mg x kg(-1) x d(-1)). Systolic blood
      pressure was significantly increased in the DOCA-salt group (240+/-11 vs 121+/-2
      mm Hg in Uni-Nx, P<0.01). Progression of hypertension was partially prevented by
      coadministration of rosiglitazone (172+/-3 mm Hg vs DOCA-salt, P<0.05) but not by
      fenofibrate. Both PPAR activators abrogated the increase in prepro-ET-1 mRNA
      content in the mesenteric vasculature of DOCA-salt rats. The media-to-lumen ratio
      was increased in DOCA-salt rats (10.3+/-0.9% vs 4.9+/-0.5% in Uni-Nx rats,
      P<0.01). Rosiglitazone and fenofibrate prevented the hypertrophic remodeling
      observed in DOCA-salt rats without affecting vascular stiffness. Rosiglitazone
      but not fenofibrate prevented endothelial dysfunction in pressurized mesenteric
      arteries. Finally, both rosiglitazone and fenofibrate prevented the vascular
      increase in superoxide anion production induced in DOCA-salt animals.
      CONCLUSIONS: PPAR-alpha and -gamma activators were able to modulate endogenous
      production of ET-1 and had beneficial vascular effects in endothelin-dependent
      hypertension.

PMID- 12524224
TI  - Peroxisome proliferator-activated receptor gamma ligands increase release of
      nitric oxide from endothelial cells.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands
      reduce lesion formation in animal models of atherosclerosis by mechanisms that
      have not been defined completely. We hypothesized that PPARgamma ligands
      stimulate endothelial-derived nitric oxide release (*NO) to protect the vascular
      wall. METHODS AND RESULTS: The PPARgamma ligands, 15-deoxy-Delta(12,14)
      prostaglandin J2 (15d-PGJ2) or ciglitazone, stimulated a PPAR response element
      luciferase reporter construct in transfected porcine pulmonary artery endothelial
      cells (PAECs), demonstrating that PPARgamma was transcriptionally functional.
      Treatment with 15d-PGJ2 or ciglitazone significantly increased release of *NO
      from PAECs or human aortic endothelial cells and augmented calcium ionophore
      induced *NO release from human umbilical vein endothelial cells measured by
      chemiluminescence analysis of culture media. Increases in *NO release caused by
      treatment with 15d-PGJ2 occurred at 24 hours, but not after 1 to 16 hours, and
      were abrogated by treatment with the transcriptional inhibitor alpha-amanitin.
      Overexpression of PPARgamma or treatment with 9-cis retinoic acid also enhanced
      PAEC *NO release. Neither 15d-PGJ2 nor ciglitazone altered eNOS mRNA, whereas 15d
      PGJ2, but not ciglitazone, decreased eNOS protein. CONCLUSIONS: Taken together,
      these findings demonstrate that PPARgamma ligands stimulate *NO release from
      endothelial cells derived from multiple vascular sites, through a transcriptional
      mechanism unrelated to eNOS expression.

PMID- 12524225
TI  - HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human
      endothelial and vascular smooth muscle cells.
AB  - OBJECTIVE: Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors
      may be mediated on the level of vascular gene transcription. The aim of this
      study was to characterize the effects of statins on the activation of
      transcription factors known to regulate inflammation and cell
      proliferation/differentiation. METHODS AND RESULTS: Simvastatin, atorvastatin,
      and lovastatin (0.1 to 10 micro mol/L) inhibited the binding of nuclear proteins
      to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA
      consensus oligonucleotides in human endothelial and vascular smooth muscle cells
      as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory
      effects of statins on NF-kappaB or AP-1-dependent transcriptional activity were
      examined by transient transfection studies. HMG-CoA reductase inhibitors
      upregulated IkappaB-alpha protein levels in endothelial cells and decreased c-Jun
      mRNA expression in smooth muscle cells as analyzed by Western and Northern
      blotting, respectively. Furthermore, statins inhibited DNA binding of hypoxia
      inducible factor-1alpha. Downstream effects of statins included inhibition of
      plasminogen activator inhibitor-1 and vascular endothelial growth factor-A mRNA
      levels in endothelial cells. CONCLUSIONS: HMG-CoA reductase inhibitors
      downregulate the activation of transcription factors NF-kappaB, AP-1, and hypoxia
      inducible factor-1alpha. These findings support the concept that statins have
      antiinflammatory and antiproliferative effects that are relevant in the treatment
      of atherosclerotic diseases.

PMID- 12524226
TI  - Cardiac ankyrin repeat protein (CARP) expression in human and murine
      atherosclerotic lesions: activin induces CARP in smooth muscle cells.
AB  - OBJECTIVE: Cardiac ankyrin repeat protein (CARP) is a transcription factor
      related protein that has been studied most extensively in the heart. In the
      present study, we investigated the expression and the potential function of CARP
      in human and murine atherosclerosis. METHODS AND RESULTS: CARP expression was
      observed by in situ hybridization in endothelial cells lining human
      atherosclerotic plaques, whereas lesion macrophages were devoid of CARP.
      Furthermore, we established that CARP mRNA and smooth muscle (SM) alpha-actin
      antigen both colocalized in a subset of intimal smooth muscle cells (SMCs),
      whereas no CARP mRNA was encountered in quiescent SMCs in the media. The CARP
      mRNA-expressing intimal SMCs were distinct from intimal SMCs that synthesized the
      activation marker osteopontin or proliferating cell nuclear antigen. In addition,
      we showed that activin A, a member of the TGFbeta superfamily that prevents SMC
      rich lesion formation, induced CARP mRNA expression in cultured SMCs.
      CONCLUSIONS: Based on our data and the knowledge that CARP reduces the
      proliferation of cultured SMCs, we propose that CARP is involved in inhibition of
      vascular lesion formation.

PMID- 12524227
TI  - Hepatocyte growth factor/scatter factor can induce angiogenesis independently of
      vascular endothelial growth factor.
AB  - OBJECTIVE: Hepatocyte growth factor/scatter factor (HGF/SF) promotes vascular
      endothelial growth factor (VEGF) expression and induces angiogenesis in multiple
      pathological conditions. The present study was designed to delineate the HGF/SF
      and VEGF signaling cascades during angiogenesis by using PTK787, a selective VEGF
      receptor antagonist. METHODS AND RESULTS: PTK787 produced a concentration
      dependent (10(-8) to 10(-6) mol/L) inhibition of VEGF-induced angiogenesis,
      without altering the basal or HGF/SF-induced response in vitro. In contrast, the
      nonspecific kinase inhibitor genistein blocked the HGF/SF-induced effect. Both
      VEGF and HGF/SF induced a rapid phosphorylation of extracellular receptor kinases
      1 and -2 (ERKs) and Akt. PTK787 inhibited the VEGF-induced activation of Akt and
      ERKs, without affecting the HGF/SF-induced phosphorylation. Treatment with VEGF
      and HGF/SF increased total neovascularization in a murine scaffold granuloma
      model, but no additive or synergistic interactions were observed. PTK787 (50
      mg/kg) blocked the VEGF-induced response without altering the basal or HGF/SF
      induced neovascularization. CONCLUSIONS: We demonstrate that HGF/SF can induce
      angiogenesis independently of VEGF, possibly through the direct activation of the
      Akt and ERKs. These results demonstrate the necessity of a multitargeted approach
      for the rational design of newer therapies to inhibit pathophysiological
      angiogenesis.

PMID- 12524228
TI  - Nutritionally induced obesity is attenuated in transgenic mice overexpressing
      plasminogen activator inhibitor-1.
AB  - OBJECTIVE: The objective of this study was to investigate the role of plasminogen
      activator inhibitor-1 (PAI-1) in adipose tissue development in vivo. METHODS AND
      RESULTS: Transgenic (Tg) mice overexpressing murine PAI-1 under control of the
      adipocyte promoter aP2 and wild-type (WT) controls were kept on standard food
      (SFD) or on high-fat diet (HFD) for 15 weeks. The body weight and the weight of
      the isolated subcutaneous and gonadal fat deposits of the Tg mice kept on the HFD
      were significantly lower than those of the WT mice. The number of adipocytes in
      the adipose tissue was similar for Tg and WT mice on the HFD, but adipocyte
      hypotrophy and a significantly lower ratio of stroma cells/adipocytes were
      observed in the Tg mice. A significant negative correlation (P<0.01) was observed
      between expression of preadipocyte factor-1, which blocks adipocyte
      differentiation, and adipose tissue weight. Fasting insulin and total cholesterol
      levels on the HFD were lower in Tg than in WT mice. CONCLUSIONS: High circulating
      PAI-1 levels attenuate nutritionally induced obesity. This may be related to
      modifications in adipose tissue cellularity affecting weight and plasma metabolic
      parameters.

PMID- 12524229
TI  - Association of hypoadiponectinemia with coronary artery disease in men.
AB  - BACKGROUND: Adiponectin is an adipocyte-derived plasma protein that accumulates
      in the injured artery and has potential antiatherogenic properties. This study
      was designed to determine whether a decreased plasma adiponectin level
      (hypoadiponectinemia) can be independently associated with the prevalence of
      coronary artery disease (CAD). METHODS AND RESULTS: The consecutive 225 male
      patients were enrolled from inpatients who underwent coronary angiography.
      Voluntary blood donors (n=225) matched for age served as controls. Plasma
      adiponectin levels in the CAD patients were significantly lower than those in the
      control subjects. Multiple logistic regression analysis including plasma
      adiponectin level, diabetes mellitus, dyslipidemia, hypertension, smoking habits,
      and body mass index revealed that hypoadiponectinemia was significantly and
      independently correlated with CAD (P<0.0088). The entire study population was
      categorized in quartiles based on the distribution of plasma adiponectin levels.
      The interquartile cutoff points were 4.0, 5.5, and 7.0 microg/mL. The
      multivariate-adjusted odds ratios for CAD in the first, second, and third
      quartiles were 2.051 (95% confidence interval [CI], 1.288 to 4.951), 1.221 (95%
      CI, 0.684 to 2.186), and 0.749 (95%CI, 0.392 to 1.418), respectively.
      CONCLUSIONS: Male patients with hypoadiponectinemia (<4.0 microg/mL) had a
      significant 2-fold increase in CAD prevalence, independent of well-known CAD risk
      factors.

PMID- 12524230
TI  - Synergistic activation of human LDL receptor expression by SCAP ligand and
      cytokine oncostatin M.
AB  - OBJECTIVE: A recent study identified a new class of compounds designated as the
      sterol-regulatory element binding protein (SREBP) cleavage-activating protein
      (SCAP) ligands that putatively bind to SCAP, leading to increased LDL receptor
      (LDLR) expression. In this study, we examined the effects of SCAP ligand GW707 in
      comparison with lovastatin and cytokine oncostatin M (OM) on the regulation of
      LDLR expression in cultured HepG2 cells. METHODS AND RESULTS: Our studies
      uncovered several new features that distinguish SCAP ligand from lovastatin, a
      classic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and
      from OM, which utilize an SREBP-independent regulatory pathway. We show that the
      induction of LDLR mRNA expression by GW707 is not affected by intracellular
      cholesterol but is completely abolished by blocking de novo protein synthesis.
      Moreover, the effects of GW707 but not lovastatin on LDLR promoter activity, mRNA
      expression, and uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanin
      perchlorate-LDL are markedly enhanced by OM. We further demonstrate that the
      amounts of the mature form of SREBP-2 translocated to the nucleus under GW707
      treatment are increased by costimulating cells with OM. CONCLUSIONS: Our studies
      provide the first evidence that higher levels of LDLR expression and function can
      be achieved through simultaneous stimulation of the SREBP-dependent and SREBP
      independent pathways, suggesting a strategy to develop an adjunct therapeutic
      intervention utilizing both pathways.

PMID- 12524231
TI  - Effects of chronic treatment with L-arginine on atherosclerosis in apoE knockout
      and apoE/inducible NO synthase double-knockout mice.
AB  - OBJECTIVE: L-arginine serves as a substrate for the formation of NO by the NO
      synthase (NOS) enzymes. In some studies, dietary supplementation of L-arginine
      reduces atherosclerosis through the restoration of NO release and improvement in
      endothelial function. In the present study, we investigate the effect of L
      arginine supplementation on the development of atherosclerosis in a mouse model.
      METHODS AND RESULTS: Apolipoprotein E (apoE) knockout (ko) and apoE/inducible NOS
      (iNOS) double-ko mice were fed a western-type diet with or without L-arginine
      supplementation in the drinking water (25 g/L). L-Arginine did not affect the
      lesion area after 16 weeks or 24 weeks in apoE ko mice. However, L-arginine
      negates the protective effect of iNOS gene deficiency. In contrast to apoE/iNOS
      dko mice without arginine supplementation, lesion areas were increased in
      apoE/iNOS double-ko mice with arginine supplementation at 24 weeks. This was
      associated with an increase in thiobarbituric acid-reactive malondialdehyde
      adducts, nitrotyrosine staining within lesions, and a decrease in the ratio of
      reduced tetrahydrobiopterin to total biopterins. CONCLUSIONS: Although L-arginine
      supplementation does not affect lesion formation in the western-type diet-fed
      apoE ko mice, it negates the protective effect of iNOS gene deficiency in this
      model. This raises the possibility that L-arginine supplementation may
      paradoxically contribute to, rather than reduce, lesion formation by mechanisms
      that involve lipid oxidation, peroxynitrite formation, and NOS uncoupling.

PMID- 12524232
TI  - Oral insulin supplementation attenuates atherosclerosis progression in
      apolipoprotein E-deficient mice.
AB  - OBJECTIVE: The role of insulin in atherosclerosis progression in diabetes is
      uncertain. We examined the effects of oral insulin supplementation on
      atherogenesis in apolipoprotein E-deficient (E(0)) mice. METHODS AND RESULTS: One
      month-old male E(0) mice were orally supplemented with human insulin (0.1, 0.5,
      and 1 U/mL) or placebo for 3 months. At the end of the study, serum and
      macrophage oxidative stress and atherosclerosis progression were studied. Insulin
      reduced lesion size by 22% to 37% (P<0.05) in all study groups. Lipid peroxides
      serum levels were 18% lower (P<0.01), and serum paraoxonase activity was 30%
      higher (P<0.01) in mice supplemented with 1.0 U/mL insulin compared with
      controls. Insulin reduced mouse peritoneal macrophage (MPM) lipid peroxides
      content and superoxide anion release by up to 44% and 62%, respectively (P<0.01).
      In addition, oral insulin reduced MPM cholesterol content and cholesterol
      biosynthesis by up to 36% and 53%, respectively (P<0.01). In vitro incubation of
      E(0) mice MPM with increasing insulin concentrations (0 to 100 micro U/mL)
      resulted in a dose-dependent reduction of cholesterol synthesis by up to 66%
      (P<0.05). CONCLUSIONS: In E(0) mice, oral insulin supplementation attenuates the
      atherosclerotic process. This may be attributable to insulin-mediated reduction
      of oxidative stress in serum and macrophages as well as reduction in macrophage
      cholesterol content.

PMID- 12524233
TI  - Elevated serum C-reactive protein and free fatty acids among nondiabetic carriers
      of missense mutations in the gene encoding lamin A/C (LMNA) with partial
      lipodystrophy.
AB  - OBJECTIVE: Dunnigan-type familial partial lipodystrophy (FPLD) due to mutant LMNA
      is a monogenic form of insulin resistance. Affected subjects, especially women,
      are at increased risk of early coronary heart disease (CHD). Although common
      insulin resistance is associated with several biochemical perturbations,
      including elevated C-reactive protein (CRP), the biochemical profile in subjects
      with mutant LMNA is incompletely defined. METHODS AND RESULTS: We studied 35
      nondiabetic adult FPLD subjects (of whom 24 were women) with either the LMNA
      R482Q or R482W missense mutations and 51 matched normal first-degree relatives
      (of whom 27 were women). Compared with normal controls, LMNA mutation carriers
      had significantly higher plasma insulin and more dyslipidemia, higher mean
      triglycerides and lower HDL cholesterol, significantly higher nonesterified free
      fatty acids and CRP, and significantly lower leptin and adiponectin than
      controls. Subgroup analyses showed that these differences were more pronounced in
      women. Other biomarkers such as resistin, fibrinogen, and plasminogen activator
      inhibitor-1 were not different between groups. CONCLUSIONS: LMNA mutations in
      nondiabetic patients with FPLD are associated with several metabolic and
      biochemical changes, particularly in women. The unfavorable profile might
      contribute to the increased susceptibility to CHD seen in LMNA mutation carriers.

PMID- 12524234
TI  - In silico quantitative trait locus map for atherosclerosis susceptibility in
      apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Atherosclerosis susceptibility is a genetic trait that varies between
      mouse strains. The goal of this study was to use a public mouse single nucleotide
      polymorphism (SNP) database to define the genetic loci that are associated with
      this trait, without the need to perform strain intercrosses that are normally
      required to obtain these loci. METHODS AND RESULTS: Apolipoprotein E (apoE)
      deficient mice on 6 inbred genetic backgrounds were compared for atherosclerosis
      lesion size in the aortic root in 2 independent studies. After normalization to
      the C57BL/6 strain that was used in both studies, lesion areas were found in the
      following rank order: DBA/2J>C57BL/6>129/SV-ter>AKR/J approximately BALB/cByJ
      approximately C3H/HeJ. The log lesion difference in phenotypes between each of
      the 15 heterologous strain pairs was determined. A mouse SNP database was then
      used to calculate the genetic differences between the 15 strain pairs in
      partially overlapping 30-cM bins across the mouse genome. Correlation analyses
      were preformed to analyze the genetic and phenotypic differences among the strain
      pairs for each genetic region. The genetic regions with the highest correlations
      define the in silico quantitative trait loci (QTL) associated with the
      atherosclerosis phenotype. Five in silico atherosclerosis QTL were identified on
      chromosomes 1, 10, 14, 15, and 18. The loci on chromosomes 1, 10, 14, and 18
      overlap with suggestive atherosclerosis QTL identified through analyses of an
      F(2) cohort derived from apoE-deficient mice on the C57BL/6 and FVB/N strains.
      CONCLUSIONS: The 5 identified in silico QTL are candidates for further study to
      confirm the presence and identity of atherosclerosis susceptibility genes within
      these loci.

PMID- 12524235
TI  - Influence of factor VIIa and phospholipids on coagulation in "acquired"
      hemophilia.
AB  - OBJECTIVE: This study was performed to evaluate the influences of phospholipids
      and recombinant factor VIIa (rFVIIa) on thrombin generation and clot formation in
      "acquired" hemophilia B. METHODS AND RESULTS: A synthetic mixture corresponding
      to hemophilia A (SHA) and "acquired" hemophilia B blood (AHBB) manufactured in
      vitro by an anti-FIX antibody were used in this study. With 10 pmol/L tissue
      factor (TF), 10 nmol/L rFVIIa, and saturating phospholipid, established thrombin
      generation in SHA was similar to that observed in the presence of factor VIII and
      rFVIIa at physiological concentrations. At lower phospholipid concentrations,
      thrombin generation was delayed and reduced. With 5 pmol/L TF, contact pathway
      inhibited AHBB clotted later than normal blood and showed reduced clot stability
      and thrombin generation. These parameters of effectiveness were increased by the
      addition of phospholipids to AHBB, which restored clot stability and increased
      thrombin generation. No correction of clot formation or thrombin generation was
      observed when rFVIIa and phospholipids were added to AHBB in the absence of TF.
      CONCLUSIONS: The influence of rFVIIa is dependent on TF, and phospholipids
      substantially increase the hemostatic (or thrombotic) potential of rFVIIa/TF.

PMID- 12524236
TI  - Effects of hyperfibrinogenemia on vasculature of C57BL/6 mice with and without
      atherogenic diet.
AB  - OBJECTIVE: Elevated fibrinogen is correlated with severe atherosclerosis, as
      defined by the occurrence of ischemic events, but the mechanistic basis for this
      correlation remains unknown. To study this relationship, we examined spontaneous
      and diet-induced atherosclerosis in transgenic mice with hyperfibrinogenemia
      (elevated fibrinogen). METHODS AND RESULTS: Normal and transgenic mice were fed
      either an atherogenic diet or simple breeder chow. We measured plasma fibrinogen
      levels and identified an age-dependent and diet-dependent increase in fibrinogen.
      After 8 to 12 months, aortic sections were prepared and stained, and lipid
      containing lesions were counted, measured, and assessed for maturity. Lipid
      filled deposits appeared spontaneously in a small number of mice on breeder chow;
      typical fatty streak-type lesions appeared in almost all of the diet-fed animals.
      Morphometric analysis showed that neither the number nor the size of lesions was
      influenced by either fibrinogen level or genotype. CONCLUSIONS: Our data showed
      that neither fibrinogen concentration nor genotype had a statistically
      significant effect on the initiation, initial growth, or early progression of
      atherosclerotic lesions.

PMID- 12524237
TI  - Extrahepatic synthesis of factor VII in human atherosclerotic vessels.
AB  - OBJECTIVE: Coagulation is initiated by the interaction of tissue factor (TF) with
      plasma coagulation factors VII (FVII) and X (FX). TF is highly expressed in
      atherosclerotic lesions, but little is known about the synthesis of FX or FVII
      outside of the liver. Previous studies suggested that macrophages synthesize
      FVII. We therefore hypothesized that macrophages within atherosclerotic lesions
      may produce FVII, leading to partial activation of the coagulation cascade.
      METHODS AND RESULTS: Immunohistochemistry was performed using antibodies against
      FVII, FX, and TF on normal and atherosclerotic vessels. In atherosclerotic
      lesions, FVII immunostaining was colocalized with TF in macrophages and spindle
      shaped smooth muscle cells. FVII mRNA was also detected in these cells using in
      situ hybridization, suggesting the local synthesis of FVII in atherosclerosis.
      Reverse transcriptase-polymerase chain reaction confirmed the presence of FVII
      mRNA in normal and atherosclerotic vessels as well as smooth muscle cells,
      fibroblasts, and keratinocytes in vitro. CONCLUSIONS: The localization of FVII
      synthesis outside the liver may be indicative of other cellular functions for
      this coagulation protein. The observed coexpression of TF and FVII may contribute
      to autocrine signaling via thrombin-independent mechanisms and may represent a
      novel mechanism contributing to growth in the setting of vascular disease.

PMID- 12524238
TI  - The serpin protease-nexin 1 is present in rat aortic smooth muscle cells and is
      upregulated in L-NAME hypertensive rats.
AB  - OBJECTIVE: Protease-nexin 1 (PN-1) belongs to the serpin superfamily and behaves
      as a specific thrombin inhibitor in the pericellular environment. Little is known
      about PN-1 expression and its regulation in the vascular system. In this study,
      we examined the expression of functionally active PN-1 in vitro in rat aortic
      smooth muscle cells and in vivo in rat arterial media and its regulation in
      hypertensive rats. METHODS AND RESULTS: The vascular PN-1 formed specific
      covalent complexes with thrombin involving the catalytic site of the protease,
      and heparin increased the formation of these complexes. We also demonstrated PN-1
      in rat arterial media by immunohistochemical staining. Moreover, we examined in
      vivo vascular expression of PN-1 in a model of chronic hypertension induced by
      long-term administration of N(G)-nitro-L-arginine methyl ester (L-NAME). Marked
      increases in PN-1 mRNA (3-fold) and protein (2-fold) were observed after 2 months
      of hypertension. Increased expression of PN-1 in the vascular wall was associated
      with an increase in the formation of complexes between radiolabeled-thrombin and
      PN-1, indicating that PN-1 was functional. CONCLUSIONS: PN-1 may thus participate
      in the mechanisms that regulate thrombin activity in the vessel wall.

PMID- 12524239
TI  - Expression of CXCL16 in human T cells.

PMID- 12524240
TI  - Constitutive activation of rac1 results in mitochondrial oxidative stress and
      induces premature endothelial cell senescence.
AB  - OBJECTIVE: Oxidative stress has been implicated in cellular senescence and
      vascular aging. We determined the role and mechanism of the small GTPase rac1 in
      vascular endothelial cell senescence. METHODS AND RESULTS: Adenoviral-mediated
      expression of the constitutively active allele of rac1 (rac1V12) in human
      umbilical vein endothelial cells resulted in mitochondrial oxidative stress with
      induction of biochemical, molecular, and morphological features of senescence.
      Suppression of mitochondrial oxidative stress abrogated rac1-induced premature
      senescence. Rac1V12 expression also resulted in an increase in endothelial
      ceramide levels. Moreover, premature endothelial cell senescence induced by an
      exogenous cell-permeable ceramide analog was not suppressed by inhibiting
      endogenous rac1 signaling. Finally, in human umbilical vein endothelial cells
      that had undergone replicative senescence, rac1 was not activated, and expression
      of the dominant-negative rac1 allele (rac1N17) did not suppress mitochondrial
      oxidative stress. CONCLUSIONS: These findings paint a picture in which the
      constitutive activation of rac1, via the generation of ceramide, results in
      mitochondrial oxidative stress and premature endothelial cell senescence.
      However, they speak against a role for endogenous rac1 activation in the
      induction of mitochondrial oxidative stress associated with replicative
      senescence of endothelial cells.

PMID- 12524241
TI  - Serum plasma pregnancy-associated protein A: a potential marker of echogenic
      carotid atherosclerotic plaques in asymptomatic hyperlipidemic subjects at high
      cardiovascular risk.
AB  - OBJECTIVE: The proteolytic activity of metalloproteinases, proinflammatory
      enzymes that degrade extracellular matrix, is elevated in lipid-rich
      atherosclerotic plaques, thereby contributing to plaque fragility and rupture.
      Pregnancy-associated plasma protein (PAPP-A) is a metalloproteinase, expressed in
      unstable atherosclerotic plaques, whose circulating levels are elevated in acute
      coronary syndromes. We evaluated serum PAPP-A levels as a marker of the premature
      development of atherosclerosis in hyperlipidemic subjects at elevated
      cardiovascular risk. METHODS AND RESULTS: Serum PAPP-A levels were determined in
      asymptomatic hyperlipidemic male subjects (n=64; mean+/-SD age, 51+/-7 years) in
      whom intima-media thickness (IMT) and lesion status in the carotid artery were
      evaluated by noninvasive ultrasonography and compared with those of a
      normolipidemic control group (n=25). No difference was observed in circulating
      PAPP-A levels between hyperlipidemic subjects and controls (8.99+/-2.93 and
      8.03+/-2.75 mIU/L, respectively; mean+/-SD) nor between hyperlipidemic subjects
      who presented with a luminal obstruction of the carotid artery (9.26+/-2.53
      mIU/L) and those who did not (8.85+/-3.29 mIU/L). By contrast, in patients with
      atheromatous carotid plaques, a positive association between serum levels of PAPP
      A and C-reactive protein was observed (P<0.05); moreover, subjects exhibiting
      hyperechoic or isoechoic, echogenic lesions had significantly higher PAPP-A
      levels compared with those with hypoechoic lesions (10.32+/-2.72 vs 8.27+/-2.18
      mIU/L, P<0.05) and with normolipidemic controls (P<0.05). CONCLUSIONS: Elevated
      serum PAPP-A levels represent a potential marker of the degree of echogenicity of
      carotid atherosclerotic plaques in asymptomatic hyperlipidemic patients at high
      cardiovascular risk and equally of an enhanced local inflammatory state involving
      remodeling of subendothelial extracellular matrix.

PMID- 12524242
TI  - Soluble CD40 ligand levels indicate lipid accumulation in carotid atheroma: an in
      vivo study with high-resolution MRI.
AB  - OBJECTIVE: The CD40/CD40 ligand pathway mediates inflammatory processes important
      in atherogenesis and the formation of the intraplaque lipid pool. We tested the
      hypothesis that plasma levels of soluble CD40 ligand are elevated in patients
      with evidence of a lipid pool on high-resolution magnetic resonance imaging (MRI)
      of carotid stenoses. METHODS AND RESULTS: We recruited 49 patients with evidence
      of carotid atherosclerosis on ultrasonography; 3 patients could not undergo
      carotid MRI because of claustrophobia. The remaining 46 patients underwent high
      resolution MRI of the carotid arteries. Two radiologists blinded to all other
      data determined the presence or absence of an intraplaque lipid pool based on the
      loss of signal between the 20-ms echo time (TE20) and the fat-suppressed TE55
      fast spin-echo images. Plasma levels of soluble CD40 ligand were determined by
      ELISA. Baseline levels of soluble CD40 ligand were higher among patients with
      evidence of intraplaque lipid (n=14) than among those without it (n=32; median,
      2.54 ng/mL; interquartile range [IQR], 1.85 to 3.52 vs median, 1.58 ng/mL; IQR,
      1.21 to 2.39; P=0.02). In contrast, soluble CD40 ligand levels were not
      correlated with percent diameter stenosis (r=-0.19; P=0.21). The relative risk
      for intraplaque lipid associated with soluble CD40 ligand levels above the median
      was 6.0 (95% confidence interval, 1.15 to 31.23; P=0.03). The magnitude of this
      predictive effect did not substantially change after adjustment for traditional
      cardiovascular risk factors (relative risk, 5.12; 95% confidence interval, 0.78
      to 33.73; P=0.09). CONCLUSIONS: Plasma levels of soluble CD40 ligand may predict
      patients with features of high-risk atherosclerotic lesions. These data provide
      novel insight into the mechanism through which elevated levels of soluble CD40
      ligand may reflect cardiovascular risk in humans and illustrate the potential
      value of interfacing high-resolution MRI with studies of vascular inflammation.

PMID- 12524244
TI  - Je peux parler!

PMID- 12524245
TI  - Is the eosinophil a "Humpty Dumpty" cell in asthma?

PMID- 12524246
TI  - Alveolar macrophages: wielding the double-edged sword of inflammation.

PMID- 12524247
TI  - Pro: modafinil has a role in management of sleep apnea.

PMID- 12524248
TI  - Con: modafinil has no role in management of sleep apnea.

PMID- 12524251
TI  - Should a pharmaceutical be approved for the broad indication of excessive
      sleepiness?

PMID- 12524252
TI  - Putting numbers to theories about periodic breathing: putting your money where
      your mouth is.

PMID- 12524253
TI  - Role of exercise and lung function in predicting work status in cystic fibrosis.
AB  - With larger numbers of adult patients with cystic fibrosis (CF) in the workplace,
      the issue of disability has arisen increasingly. We examined relationships
      between measures of pulmonary impairment and work/school capability and then
      determined whether quantification of aerobic fitness improved predictability of
      disease-related disability. We studied 73 patients with CF who performed lung
      function and exercise capacity tests, completed a work/education questionnaire,
      and were scored for clinical and chest radiographic status. Patients who were
      characterized as unemployed and in poor health had more severe pulmonary disease
      according to American Thoracic Society impairment/disability criteria. Subjects
      were further classified into three groups based on employment or education status
      over the preceding 12 months. FEV1, maximal oxygen consumption, Schwachman
      Kulczycki clinical and Brasfield radiographic scores, and frequency of pulmonary
      exacerbations over 2 years were associated with disability, but change in FEV1
      over 2 years and oxygen saturation at rest or exertion were not. FEV1 and
      Schwachman-Kulczycki scores were the best independent predictors of
      impairment/disability; specific thresholds used in other pulmonary diseases were
      of limited utility. We conclude that after accounting for either current level of
      FEV1 or Schwachman-Kulczycki scores, no other physiological or clinical measures
      contribute to predicting limitation in a work or school environment.

PMID- 12524254
TI  - Platelet endothelial cell adhesion molecule-1 in neutrophil emigration during
      acute bacterial pneumonia in mice and rats.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is an adhesion
      molecule believed to mediate transendothelial migration of neutrophils and other
      leukocytes after CD11/CD18-mediated adhesion. Our study evaluated the role of
      PECAM-1 in neutrophil emigration across the pulmonary capillaries and the
      bronchial microvasculature using blocking anti-PECAM-1 antibodies in mice and
      rats. Neutrophil emigration was induced by Escherichia coli, a stimulus eliciting
      CD11/CD18-dependent emigration, or Streptococcus pneumoniae, a stimulus inducing
      CD11/CD18-independent emigration. Although anti-PECAM-1 antibodies partially
      inhibited glycogen-induced neutrophil emigration into the peritoneum, neutrophil
      emigration across either the pulmonary capillaries or the bronchial
      microvasculature in response to either E. coli or S. pneumoniae was not prevented
      when the function of PECAM-1 was inhibited in either mice or rats. There was also
      no increase in the number of intravascular neutrophils within the bronchial
      vessels after treatment with anti-PECAM-1 antibody. These studies indicate that
      either CD11/CD18-dependent or -independent adhesion pathways may lead to PECAM-1
      independent transendothelial migration through the pulmonary or the bronchial
      endothelium.

PMID- 12524255
TI  - The promoter polymorphism in the eosinophil cationic protein gene and its
      influence on the serum eosinophil cationic protein level.
AB  - Asthma is characterized by reversible airway obstruction and airway inflammation.
      Serum levels of eosinophil cationic protein (ECP) might reflect eosinophilic
      airway inflammation and asthma activity. However, serum ECP levels are not
      elevated in some patients with asthma, even when they are symptomatic. In this
      study, we screened for polymorphisms in the ECP gene and analyzed association
      between these polymorphisms and asthma and serum ECP levels in 137 Japanese
      families identified through children with asthma. We identified three
      polymorphisms (-393C/T, -38C/A, and 124Arg/Thr) in human ECP. We did not find
      associations between these polymorphisms and asthma by the transmission
      disequilibrium test. However, we found that serum ECP levels in subjects with the
      -393T allele were significantly lower than those in subjects with the -393C
      allele. A reporter construct with the -393T allele showed significantly lower
      promoter activity than one with the -393C allele. Gel shift assay revealed that
      C/EBP proteins can bind the -393C/T polymorphic site. These data indicate that
      C/EBP proteins play an important role in the regulation of ECP and that a
      significant amount of the variance in baseline serum ECP levels may be explained
      by the -393C/T polymorphism. Although ECP polymorphisms are not likely to be
      involved in the development of asthma, measurement of ECP levels for the
      assessment of asthma activity may be improved when done in combination with
      genotyping of the -393C/T polymorphism.

PMID- 12524256
TI  - Early changes in alveolar fluid clearance by nitric oxide after endotoxin
      instillation in rats.
AB  - Alveolar fluid clearance may be inhibited and/or stimulated under pathologic
      conditions. We examined the early change of alveolar fluid clearance after
      endotoxin instillation in adult rats. We employed electron paramagnetic resonance
      nitric oxide (NO) trapping technique with iron complex with N,N
      diethyldithiocarbamate as an NO trapping agent. We found that lung NO signals
      reached the highest magnitude by 6 hours after endotoxin instillation. NO
      production was accompanied by increases in lung cyclic guanosine monophosphate
      levels. Alveolar fluid clearance decreased significantly 6 hours after the
      administration of the endotoxin and increased further at 24 hours. These changes
      were shown to be related to the function of amiloride-sensitive sodium ion
      channels. Treatment with gadolinium chloride and aminoguanidine significantly
      decreased lung NO and cyclic guanosine monophosphate levels and completely
      ameliorated the decrease in alveolar fluid clearance. In addition, the increase
      in alveolar fluid clearance at 24 hours returned to normal levels after treatment
      with gadolinium chloride and aminoguanidine. We found immunoreactive inducible
      nitric oxide synthase to be abundantly expressed in the cytoplasm of alveolar
      macrophages. Our results suggest that alveolar endotoxin inhibits alveolar fluid
      clearance at 6 hours by NO. NO is produced via inducible NO synthase in endotoxin
      stimulated alveolar macrophages and was also shown to increase alveolar fluid
      clearance at 24 hours.

PMID- 12524257
TI  - ATS/ACCP Statement on cardiopulmonary exercise testing.

PMID- 12524258
TI  - Delay in diagnosis among hospitalized patients with active tuberculosis-
      predictors and outcomes.

PMID- 12524259
TI  - A possible antiinflammatory treatment for cystic fibrosis.

PMID- 12524260
TI  - Lighting up single ion channels.

PMID- 12524261
TI  - Untangling ligand induced activation and desensitization of G-protein-coupled
      receptors.
AB  - Long-term treatment with a drug to a G-protein-coupled receptor (GPCR) often
      leads to receptor-mediated desensitization, limiting the therapeutic lifetime of
      the drug. To better understand how this therapeutic window might be controlled,
      we created a mechanistic Monte Carlo model of the early steps in GPCR signaling
      and desensitization. Using this model we found that the rates of G-protein
      activation and receptor phosphorylation can be partially decoupled by varying the
      drug-receptor dissociation rate constant, k(off), and the drug's efficacy, alpha.
      The maximum ratio of G-protein activation to receptor phosphorylation (GARP) was
      found for drugs with an intermediate k(off) value and small alpha-value. Changes
      to the cellular environment, such as changes in the diffusivity of membrane
      molecules and the G-protein inactivation rate constant, affected the GARP value
      of a drug but did not change the characteristic shape of the GARP curve. These
      model results are examined in light of experimental data for a number of GPCRs
      and are found to be in good agreement, lending support to the idea that the
      desensitization properties of a drug might be tailored to suit a specific
      application.

PMID- 12524263
TI  - Buffers and oscillations in intracellular Ca2+ dynamics.
AB  - I model the behavior of intracellular Ca(2+) release with high buffer
      concentrations. The model uses a spatially discrete array of channel clusters.
      The channel subunit dynamics is a stochastic representation of the DeYoung-Keizer
      model. The calculations show that the concentration profile of fast buffer around
      an open channel is more localized than that of slow buffers. Slow buffers allow
      for release of larger amounts of Ca(2+) from the endoplasmic reticulum and hence
      bind more Ca(2+) than fast buffers with the same dissociation constant and
      concentration. I find oscillation-like behavior for high slow buffer
      concentration and low Ca(2+) content of the endoplasmic reticulum. High
      concentration of slow buffer leads to oscillation-like behavior by repetitive
      wave nucleation for high Ca(2+) content of the endoplasmic reticulum.
      Localization of Ca(2+) release by slow buffer, as used in experiments, can be
      reproduced by the modeling approach.

PMID- 12524262
TI  - Pores formed by the nicotinic receptor m2delta Peptide: a molecular dynamics
      simulation study.
AB  - The M2delta peptide self-assembles to form a pentameric bundle of transmembrane
      alpha-helices that is a model of the pore-lining region of the nicotinic
      acetylcholine receptor. Long (>15 ns) molecular dynamics simulations of a model
      of the M2delta(5) bundle in a POPC bilayer have been used to explore the
      conformational dynamics of the channel assembly. On the timescale of the
      simulation, the bundle remains relatively stable, with the polar pore-lining side
      chains remaining exposed to the lumen of the channel. Fluctuations at the helix
      termini, and in the helix curvature, result in closing/opening transitions at
      both mouths of the channel, on a timescale of approximately 10 ns. On average,
      water within the pore lumen diffuses approximately 4x more slowly than water
      outside the channel. Examination of pore water trajectories reveals both single
      file and path-crossing regimes to occur at different times within the simulation.

PMID- 12524264
TI  - On the role of stochastic channel behavior in intracellular Ca2+ dynamics.
AB  - I present a stochastic model for intracellular Ca(2+) oscillations. The model
      starts from stochastic binding and dissociation of Ca(2+) to binding sites on a
      single subunit of the IP(3)-receptor channel but is capable of simulating large
      numbers of clusters for many oscillation periods too. I find oscillations with
      variable periods ranging from 17 s to 120 s and a standard deviation well in the
      experimentally observed range. Long period oscillations can be perceived as
      nucleation phenomenon and can be observed for a large variety of single channel
      dynamics. Their period depends on the geometric characteristics of the cluster
      array. Short periods are in the range of the time scale of channel dynamics. Both
      long and short period oscillations occur for parameters with a nonoscillatory
      deterministic regime.

PMID- 12524265
TI  - Explicit water near the catalytic I helix Thr in the predicted solution structure
      of CYP2A4.
AB  - The solution structure of mouse cytochrome P450 2A4 (CYP2A4), a monooxygenase of
      deoxysteroids, was obtained using homology modeling and molecular dynamics. The
      solvent-equilibrated CYP2A4 preserves the essential features of CYP450s. A
      comparison of the models CYP2A4 and CYP2A4 with testosterone bound CYP2A4/T
      illustrates the changes induced by the binding of the substrate. Experimental
      evidence links four amino acid residues to the catalytic activity, substrate
      specificity, and regioselectivity of this enzyme. Three of the four amino acids
      are found within contact distance of the testosterone substrate, and therefore
      may control the binding of the substrate through direct interaction. Remarkably,
      a water complex previously observed in x-ray crystal structure forms near the
      bulge in the central I helix that contains a conserved Thr. The properties of the
      I helix are computed in the context of the presence or absence of ligand.

PMID- 12524266
TI  - A model of the oscillatory metabolism of activated neutrophils.
AB  - We present a two-compartment model to explain the oscillatory behavior observed
      experimentally in activated neutrophils. Our model is based mainly on the
      peroxidase-oxidase reaction catalyzed by myeloperoxidase with melatonin as a
      cofactor and NADPH oxidase, a major protein in the phagosome membrane of the
      leukocyte. The model predicts that after activation of a neutrophil, an increase
      in the activity of the hexose monophosphate shunt and the delivery of
      myeloperoxidase into the phagosome results in oscillations in oxygen and NAD(P)H
      concentration. The period of oscillation changes from >200 s to 10-30 s. The
      model is consistent with previously reported oscillations in cell metabolism and
      oxidant production. Key features and predictions of the model were confirmed
      experimentally. The requirement of the hexose monophosphate pathway for 10 s
      oscillations was verified using 6-aminonicotinamide and dexamethasone, which are
      inhibitors of glucose-6-phosphate dehydrogenase. The role of the NADPH oxidase in
      promoting oscillations was confirmed by dose-response studies of the effect of
      diphenylene iodonium, an inhibitor of the NADPH oxidase. Moreover, the model
      predicted an increase in the amplitude of NADPH oscillations in the presence of
      melatonin, which was confirmed experimentally. Successful computer modeling of
      complex chemical dynamics within cells and their chemical perturbation will
      enhance our ability to identify new antiinflammatory compounds.

PMID- 12524267
TI  - Structural preference for changes in the direction of the Ca2+-induced
      transition: a study of the regulatory domain of skeletal troponin-C.
AB  - The determinants for specificity in the Ca(2+)-dependent response of the
      regulatory N-terminal domain of skeletal troponin-C are a combination of
      intrinsic and induced properties. We characterized computationally the intrinsic
      propensity of this domain for structural changes similar to those observed
      experimentally in the Ca(2+)-induced transition. The preference for such changes
      was assessed by comparing the structural effect of the harmonic and quasiharmonic
      vibrations specific for each Ca(2+) occupancy with crystallographic data. Results
      show that only the Ca(2+)-saturated form of the protein features a slow
      vibrational motion preparatory for the transition. From the characteristics of
      this mode, we identified a molecular mechanism for transition, by which residues
      42-51 of helix B and of the adjacent linker move toward helices (A, D), and bind
      to the surface used by the protein to interact with troponin-I. By obstructing
      the access of the target to hydrophobic residues important in the formation of
      the complex, helix B and the adjacent linker act as an autoinhibitory structural
      element. Specific properties of the methionines at the interaction surface were
      found to favor the binding of the autoinhibitory region. Located over hydrophobic
      residues critical for binding, the methionines are easily displaceable to
      increase the accessibility of these residues to molecular encounter.

PMID- 12524268
TI  - Structure and dynamics of interfacial water in an Lalpha phase lipid bilayer from
      molecular dynamics simulations.
AB  - Based on molecular dynamics simulations, an analysis of structure and dynamics is
      performed on interfacial water at a liquid crystalline
      dipalmitoylphosphatidycholine/water system. Water properties relevant for
      understanding NMR relaxation are emphasized. The first and second rank
      orientational order parameters of the water O-H bonds were calculated, where the
      second rank order parameter is in agreement with experimental determined
      quadrupolar splittings. Also, two different interfacial water regions (bound
      water regions) are revealed with respect to different signs of the second rank
      order parameter. The water reorientation correlation function reveals a mixture
      of fast and slow decaying parts. The fast (ps) part of the correlation function
      is due to local anisotropic water reorientation whereas the much slower part is
      due to more complicated processes including lateral diffusion along the interface
      and chemical exchange between free and bound water molecules. The 100-ns-long
      molecular dynamics simulation at constant pressure (1 atm) and at a temperature
      of 50 degrees C of 64 lipid molecules and 64 x 23 water molecules lack a slow
      water reorientation correlation component in the ns time scale. The (2)H(2)O
      powder spectrum of the dipalmitoylphosphatidycholine/water system is narrow and
      consequently, the NMR relaxation time T(2) is too short compared to experimental
      results.

PMID- 12524269
TI  - A two-compartment model of osmotic lysis in Plasmodium falciparum-infected
      erythrocytes.
AB  - We recently identified a voltage-dependent anion channel on the surface of human
      red blood cells (RBCs) infected with the malaria parasite, Plasmodium falciparum.
      This channel, the plasmodial erythrocyte surface anion channel (PESAC), likely
      accounts for the increased permeability of infected RBCs to various small
      solutes, as assessed quantitatively with radioisotope flux and patch-clamp
      studies. Whereas this increased permeability has also been studied by following
      osmotic lysis of infected cells in permeant solutes, these experiments have been
      limited to qualitative comparisons of lysis rates. To permit more quantitative
      examination of lysis rates, we have developed a mathematical model for osmotic
      fragility of infected cells based on diffusional uptake via PESAC and the two
      compartment geometry of infected RBCs. This model, combined with a simple light
      scattering assay designed to track osmotic lysis precisely, produced permeability
      coefficients that match both previous isotope flux and patch-clamp estimates. Our
      model and light scattering assay also revealed Michaelian kinetics for inhibition
      of PESAC by furosemide, suggesting a 1:1 stoichiometry for their interaction.

PMID- 12524270
TI  - The importance of thermodynamic equilibrium for high throughput gene expression
      arrays.
AB  - We present an analysis of physical chemical constraints on the accuracy of DNA
      micro-arrays under equilibrium and nonequilibrium conditions. At the beginning of
      the article we describe an algorithm for choosing a probe set with high
      specificity for targeted genes under equilibrium conditions. The algorithm as
      well as existing methods is used to select probes from the full Saccharomyces
      cerevisiae genome, and these probe sets, along with a randomly selected set, are
      used to simulate array experiments and identify sources of error. Inasmuch as
      specificity and sensitivity are maximum at thermodynamic equilibrium, we are
      particularly interested in the factors that affect the approach to equilibrium.
      These are analyzed later in the article, where we develop and apply a rapidly
      executable method to simulate the kinetics of hybridization on a solid phase
      support. Although the difference between solution phase and solid phase
      hybridization is of little consequence for specificity and sensitivity when
      equilibrium is achieved, the kinetics of hybridization has a pronounced effect on
      both. We first use the model to estimate the effects of diffusion,
      crosshybridization, relaxation time, and target concentration on the
      hybridization kinetics, and then investigate the effects of the most important
      kinetic parameters on specificity. We find even when using probe sets that have
      high specificity at equilibrium that substantial crosshybridization is present
      under nonequilibrium conditions. Although those complexes that differ from
      perfect complementarity by more than a single base do not contribute to sources
      of error at equilibrium, they slow the approach to equilibrium dramatically and
      confound interpretation of the data when they dissociate on a time scale
      comparable to the time of the experiment. For the best probe set, our simulation
      shows that steady-state behavior is obtained in a relaxation time of
      approximately 12-15 h for experimental target concentrations approximately (10(
      13) - 10(-14))M, but the time is greater for lower target concentrations in the
      range (10(-15)-10(-16))M. The result points to an asymmetry in the accuracy with
      which up- and downregulated genes are identified.

PMID- 12524271
TI  - Statistical mechanics of sequence-dependent circular DNA and its application for
      DNA cyclization.
AB  - DNA cyclization is potentially the most powerful approach for systematic
      quantitation of sequence-dependent DNA bending and flexibility. We extend the
      statistical mechanics of the homogeneous DNA circle to a model that considers
      discrete basepairs, thus allowing for inhomogeneity, and apply the model to
      analysis of DNA cyclization. The theory starts from an iterative search for the
      minimum energy configuration of circular DNA. Thermodynamic quantities such as
      the J factor, which is essentially the ratio of the partition functions of
      circular and linear forms, are evaluated by integrating the thermal fluctuations
      around the configuration under harmonic approximation. Accurate analytic
      expressions are obtained for equilibrium configurations of homogeneous circular
      DNA with and without bending anisotropy. J factors for both homogeneous and
      inhomogeneous DNA are evaluated. Effects of curvature, helical repeat, and
      bending and torsional flexibility in DNA cyclization are analyzed in detail,
      revealing that DNA cyclization can detect as little as one degree of curvature
      and a few percent change in flexibility. J factors calculated by our new approach
      are well consistent with Monte Carlo simulations, whereas the new theory has much
      greater efficiency in computations. Simulation of experimental results has been
      demonstrated.

PMID- 12524272
TI  - Near-critical phenomena in intracellular metabolite pools.
AB  - The supply and consumption of metabolites in living cells are catalyzed by
      enzymes. Here we consider two of the simplest schemes where one substrate is
      eliminated through Michaelis-Menten kinetics, and where two types of substrates
      are joined together by an enzyme. It is demonstrated how steady-state substrate
      concentrations can change ultrasensitively in response to changes in their supply
      rates and how this is coupled to slow relaxation back to steady state after a
      perturbation. In the one-substrate system, such near-critical behavior occurs
      when the supply rate approaches the maximal elimination rate, and in the two
      substrate system it occurs when the rates of substrate supply are almost
      balanced. As systems that operate near criticality tend to display large random
      fluctuations, we also carried out a stochastic analysis using analytical
      approximations of master equations and compared the results with molecular-level
      Monte Carlo simulations. It was found that the significance of random
      fluctuations was directly coupled to the steady-state sensitivity and that the
      two substrates can fluctuate greatly because they are anticorrelated in such a
      way that the product formation rate displays only small variation. Basic
      relations are highlighted and biological implications are discussed.

PMID- 12524273
TI  - Molecular dynamics simulations on SDF-1alpha: binding with CXCR4 receptor.
AB  - Insights into the interacting mode of CXCR4 with SDF-1alpha are crucial in
      understanding the structural and functional characteristics of CXCR4 receptor. In
      this paper a computational pipeline, integrating protein structure prediction,
      molecular dynamics simulations, automated molecular docking, and Brownian
      dynamics simulations were employed to investigate the dynamic and energetic
      aspects of CXCR4 associating with SDF-1alpha. The entire simulation revealed the
      surface distribution feature of electrostatic potentials and conformational "open
      close" process of the receptor. The possible binding conformation of CXCR4 was
      identified, and the CXCR4-SDF-1alpha binding complex was generated. Arg188-Glu277
      salt bridge plays an important role for both the extracellular domain
      conformational change and SDF-1alpha binding. Two binding sites were mapped at
      the extracellular domain (Site 1) and inside the transmembrane domain (Site 2),
      which are composed of conserved residues. Sites 1 and 2 contribute approximately
      60% and 40% to the binding affinity with SDF-1alpha, respectively. The binding
      model is in agreement with most of the experimental data. Transmembrane VI has
      more significant motion in the harmonious conformational transition of CXCR4
      during SDF-1alpha binding, which may be possibly associated with signal
      transduction. Based on the modeling and simulation, a binding mechanism
      hypothesis between CXCR4 and SDF-1alpha and its relationship to the signal
      transduction has been proposed.

PMID- 12524274
TI  - Solution NMR studies of antiamoebin, a membrane channel-forming polypeptide.
AB  - Antiamoebin I is a membrane-active peptaibol produced by fungi of the species
      Emericellopsis which is capable of forming ion channels in membranes. Previous
      structure determinations by x-ray crystallography have shown the molecule is
      mostly helical, with a deep bend in the center of the polypeptide, and that the
      backbone structure is independent of the solvent used for crystallization. In
      this study, the solution structure of antiamoebin was determined by NMR
      spectroscopy in methanol, a solvent from which one of the crystal structures was
      determined. The ensemble of structures produced exhibit a right-handed helical C
      terminus and a left-handed helical conformation toward the N-terminus, in
      contrast to the completely right-handed helices found in the crystal structures.
      The NMR results also suggest that a "hinge" region exists, which gives
      flexibility to the polypeptide in the central region, and which could have
      functional implications for the membrane insertion process. A model for the
      membrane insertion and assembly process is proposed based on the antiamoebin
      solution and crystal structures, and is contrasted with the assembly and
      insertion mechanism proposed for other ion channel-forming polypeptides.

PMID- 12524275
TI  - Effect of external pH on activation of the Kv1.5 potassium channel.
AB  - We studied the mechanism by which external acidification from pH 7.3 to 6.8
      reduced current magnitude in the Kv1.5 potassium channel. At physiological
      external [K(+)], a shift in the voltage-dependence of activation was entirely
      responsible for the acidification-induced decrease in Kv1.5 current magnitude (pK
      = 7.15). Elevation of external [Ca(2+)] or [Mg(2+)] identically shifted
      activation curves to the right and identically shifted the pH-sensitivity of the
      activation curves to more acidic values. Similar observations were made with the
      Kv2.1 K(+) channel, except that the pK for the activation shift was out of the
      physiological range. These data are consistent with a mechanism by which
      acidification shifted activation via modification of a local surface potential.
      Elimination of eight positive charges within the outer vestibule of the
      conduction pathway had no effect on the voltage-dependence of activation at pH
      7.3 or higher, which suggested that sites exposed to the conduction pathway
      within the outer vestibule did not directly contribute to the relevant local
      surface potential. However, mutations at position 487 (within the conduction
      pathway) displaced the pK of the pH-sensitive shift in activation, such that the
      sensitivity of Kv1.5 current to physiologically relevant changes in pH was
      reduced or eliminated. These results suggest that, among voltage-gated K(+)
      channels, activation in Kv1.5 is uniquely sensitive to physiologically relevant
      changes in pH because the pK for the sites that contribute to the local surface
      potential effect is near pH 7. Moreover, the pK for the activation shift depends
      not only on the nature of the sites involved but also on structural orientation
      conferred, in part, by at least one residue within the conduction pathway.

PMID- 12524276
TI  - Voltage-dependent blockade of connexin40 gap junctions by spermine.
AB  - The effects of spermine and spermidine, endogenous polyamines that block many
      forms of ion channels, were investigated in homotypic connexin (Cx)-40 gap
      junctions expressed in N2A cells. Spermine blocked up to 95% of I(j) through
      homotypic Cx40 gap junctions in a concentration- and transjunctional voltage
      (V(j))-dependent manner. V(j) was varied from 5 to 50 mV in 5-mV steps and the
      dissociation constants (K(m)) were determined from spermine concentrations
      ranging from 10 micro M to 2 mM. The K(m) values ranged from 4.9 mM to 107 micro
      M for 8.6 < or = V(j) < or = 37.7 mV, within the physiological range of
      intracellular spermine for V(j) > or = 20 mV. The K(m) values for spermidine were
      > or = 5 mM. Estimates of the electrical distance (delta) for spermine (z = +4)
      and spermidine (z = +3) were 0.96 and 0.76 respectively. Cx40 single channel
      conductance was 129 pS in the presence of 2-mM spermine and channel open
      probability was significantly reduced in a V(j)-dependent manner. Similar
      concentrations of spermine did not block I(j) through homotypic Cx43 gap
      junctions, indicating that spermine selectively blocks Cx40 gap junctions. This
      is contrary to our previous findings that large tetraalkylammonium ions, also
      known to block several forms of ion channels, block junctional currents (I(j))
      through homotypic connexin Cx40 and Cx43 gap junctions.

PMID- 12524277
TI  - Truncation of the carboxyl terminus of the dihydropyridine receptor beta1a
      subunit promotes Ca2+ dependent excitation-contraction coupling in skeletal
      myotubes.
AB  - We investigated the contribution of the carboxyl terminus region of the beta1a
      subunit of the skeletal dihydropyridine receptor (DHPR) to the mechanism of
      excitation-contraction (EC) coupling. cDNA-transfected beta1 KO myotubes were
      voltage clamped, and Ca(2+) transients were analyzed by confocal fluo-4
      fluorescence. A chimera with an amino terminus half of beta2a and a carboxyl
      terminus half of beta1a (beta2a 1-287/beta1a 325-524) recapitulates skeletal-type
      EC coupling quantitatively and was used to generate truncated variants lacking 7
      to 60 residues from the beta1a-specific carboxyl terminus (Delta7, Delta21,
      Delta29, Delta35, and Delta60). Ca(2+) transients recovered by the control
      chimera have a sigmoidal Ca(2+) fluorescence (DeltaF/F) versus voltage curve with
      saturation at potentials more positive than +30 mV, independent of external
      Ca(2+) and stimulus duration. In contrast, the amplitude of Ca(2+) transients
      expressed by the truncated variants varied with the duration of the pulse, and
      for Delta29, Delta35, and Delta60, also varied with external Ca(2+)
      concentration. For Delta7 and Delta21, a 50-ms depolarization produced a
      sigmoidal DeltaF/F versus voltage curve with a lower than control maximum
      fluorescence. Moreover, for Delta29, Delta35, and Delta60, a 200-ms
      depolarization increased the maximum fluorescence and changed the shape of the
      DeltaF/F versus voltage curve, from sigmoidal to bell-shaped, with a maximum at
      approximately +30 mV. The change in voltage dependence, together with the
      external Ca(2+) dependence and additional controls with ryanodine, indicated a
      loss of skeletal-type EC coupling and the emergence of an EC coupling component
      triggered by the Ca(2+) current. Analyses of d(DeltaF/F)/dt showed that the rate
      of cytosolic Ca(2+) increase during the Ca(2+) transient was fivefold faster for
      the control chimera than for the severely truncated variants (Delta29, Delta35,
      and Delta60) and was consistent with the kinetics of the DHPR Ca(2+) current. In
      summary, absence of the beta1a-specific carboxyl terminus (last 29 to 60 residues
      of the control chimera) results in a loss of the fast component of the Ca(2+)
      transient, bending of the DeltaF/F versus voltage curve, and emergence of EC
      coupling triggered by the Ca(2+) current. The studies underscore the essential
      role of the carboxyl terminus region of the DHPR beta1a subunit in fast voltage
      dependent EC coupling in skeletal myotubes.

PMID- 12524278
TI  - Proton transfer in gramicidin channels is modulated by the thickness of
      monoglyceride bilayers.
AB  - The thickness of monoglyceride planar bilayers has significant effects on the
      transfer of protons in both native gramicidin A (gA) and in covalently linked SS-
      and RR-dioxolane-linked gA proteins. Planar bilayers with various thicknesses
      were formed from an appropriate combination of monoglyceride with various fatty
      acid lengths and solvent. Bilayer thicknesses ranged from 25 A (monoolein in
      squalene) to 54 A (monoeicosenoin in decane). Single-channel conductances to
      protons (g(H)) were measured in the concentration range of 10-5000 mM HCl. In
      native gA as well as in RR channels, the shape of the log(g(H))-log([H(+)])
      relationships was nonlinear and remained basically unaltered in monoglyceride
      bilayers with various thicknesses. For both native gA and RR channels, g(H)
      values were systematically and significantly larger in thin than in thick
      bilayers. By contrast, the shape of the log(g(H))-log([H(+)]) relationships in
      the SS channel was linear (with a slope considerably smaller than 1) in thick
      (>37 A) bilayers. However, in thin (<37 A) bilayers these plots became nonlinear
      and g(H) values approached those obtained in native gA channels. The
      linearization of the log-log plots in the SS channel in thick bilayers is a
      consequence of a dramatic increase (instead of a decrease as in native gA and RR
      channels) of g(H) in these bilayers in [H(+)] <1 M. The gating characteristics of
      the various gA channels as a function of bilayer thickness followed the same
      pattern as described previously. It was noticed, however, that in the thickest
      monoglyceride bilayer used in this study, both the SS- and RR-dioxolane-linked
      channels opened in a mode of bursting activity instead of remaining in the open
      state as in thin bilayers. It is proposed that the thickness of monoglyceride
      bilayers modulates proton transfer in native gA channels by a combination of
      factors including the access resistances of channels to H(+), and fluctuations in
      both the structure of the lipid bilayer and in the distance between gA monomers.
      The differential effects of relatively thick monoglyceride bilayers on proton
      transfer in both dioxolane-linked gA channels must relate to distinct
      interactions between the bilayers and the SS and RR dioxolanes.

PMID- 12524279
TI  - Intramembrane charge movement and L-type calcium current in skeletal muscle
      fibers isolated from control and mdx mice.
AB  - Dystrophin-deficient muscle fibers from mdx mice are believed to suffer from
      increased calcium entry and elevated submembranous calcium level, the actual
      source and functional consequences of which remain obscure. Here we compare the
      properties of the dihydropyridine receptor as voltage sensor and calcium channel
      in control and mdx muscle fibers, using the silicone-voltage clamp technique. In
      control fibers charge movement followed a two-state Boltzmann distribution with
      values for maximal charge, midpoint voltage, and steepness of 23 +/- 2 nC/ micro
      F, -37 +/- 3 mV, and 13 +/- 1 mV (n = 7). Essentially identical values were
      obtained in mdx fibers and the time course of charge recovery from inactivation
      was also similar in the two populations (tau approximately 6 s). In control
      fibers the voltage dependence of the slow calcium current elicited by 100-ms-long
      pulses gave values for maximal conductance, apparent reversal potential, half
      activation potential, and steepness factor of 156 +/- 15 S/F, 65.5 +/- 2.9 mV, 
      0.76 +/- 1.2 mV, and 6.2 +/- 0.5 mV (n = 17). In mdx fibers, the half-activation
      potential of the calcium current was slightly more negative (-6.2 +/- 1.2 mV, n =
      16). Also, when using longer pulses, the time constant of calcium current decay
      was found to be significantly larger (by a factor of 1.5-2) in mdx than in
      control fibers. These changes in calcium current properties are unlikely to be
      primarily responsible for a dramatic alteration of intracellular calcium
      homeostasis. They may be speculated to result, at least in part, from remodeling
      of the submembranous cytoskeleton network due to the absence of dystrophin.

PMID- 12524280
TI  - Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.
AB  - K(ATP) channels are comprised of a pore-forming protein, Kir6.x, and the
      sulfonylurea receptor, SURx. Interaction of adenine nucleotides with Kir6.2
      positively charged amino acids such as K185 and R201 on the C-terminus causes
      channel closure. Substitution of these amino acids with other positively charged
      residues had small effects on inhibition by adenine nucleotide, while
      substitution with neutral or negative residues had major effects, suggesting
      electrostatic interactions between Kir6.2 positive charges and adenine nucleotide
      negative phosphate groups. Furthermore, R201 mutation decreased channel
      sensitivity to ATP, ADP, and AMP to a similar extent, but K185 mutation decreased
      primarily ATP and ADP sensitivity, leaving the AMP sensitivity relatively
      unaffected. Thus, channel inhibition by ATP may involve interaction of the alpha
      phosphate with R201 and interaction of the beta-phosphate with K185. In addition,
      decreased open probability due to rundown or sulfonylureas caused an increase in
      ATP sensitivity in the K185 mutant, but not in the R201 mutant. Thus, the beta
      phosphate may bind in a state-independent fashion to K185 to destabilize channel
      openings, while R201 interacts with the alpha-phosphate to stabilize a channel
      closed configuration. Substitution of R192 on the C-terminus and R50 on the N
      terminus with different charged residues also affected ATP sensitivity. Based on
      these results a structural scheme is proposed, which includes features of other
      recently published models.

PMID- 12524281
TI  - Effect of external magnesium and calcium on human connexin46 hemichannels.
AB  - One of the most striking features of hemi-gap-junctional channels is that they
      are dramatically modulated by extracellular divalent cations. In this study, we
      characterized the effects of external divalent cations and voltage on macroscopic
      human connexin46 (hCx46) hemi-gap-junctional currents using the two-electrode
      voltage-clamp technique. Increasing extracellular magnesium resulted in a shift
      of the voltage dependence of activation to more positive potentials, a decrease
      in the maximum conductance, an acceleration of deactivation, and a slowing of
      activation. Hyperpolarizing the membrane potential could mimic the effect of
      raising external magnesium on the activation kinetics and maximum conductance.
      These results could be interpreted in terms of a sequential model of channel
      activation with two independent divalent cation binding sites. This model could
      also explain the effects of external calcium on hCx46 hemichannels. However, the
      apparent binding affinities for calcium were significantly higher than for
      magnesium. In addition, we identified a mutation in the first extracellular
      domain of hCx46 (hCx46*N63S) that resulted in hemichannels that showed increased
      sensitivity to magnesium blockade.

PMID- 12524282
TI  - Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer
      vestibule.
AB  - The highly selective sodium channel blocker, tetrodotoxin (TTX) has been
      instrumental in characterization of voltage-gated sodium channels. TTX occludes
      the ion-permeation pathway at the outer vestibule of the channel. In addition to
      a critical guanidinium group, TTX possesses six hydroxyl groups, which appear to
      be important for toxin block. The nature of their interactions with the outer
      vestibule remains debatable, however. The C-11 hydroxyl (C-11 OH) has been
      proposed to interact with the channel through a hydrogen bond to a carboxyl
      group, possibly from domain IV. On the other hand, previous experiments suggest
      that TTX interacts most strongly with pore loops of domains I and II. Energetic
      localization of the C-11 OH was undertaken by thermodynamic mutant cycle analysis
      assessing the dependence of the effects of mutations of the adult rat skeletal
      muscle Na(+) channel (rNa(v)1.4) and the presence of C-11 OH on toxin IC(50).
      Xenopus oocytes were injected with the mutant or native Na(+) channel mRNA, and
      currents were measured by two-electrode voltage clamp. Toxin blocking efficacy
      was determined by recording the reduction in current upon toxin exposure. Mutant
      cycle analysis revealed that the maximum interaction of the C-11 OH was with
      domain IV residue D1532 (DeltaDeltaG: 1.0 kcal/mol). Furthermore, C-11 OH had
      significantly less interaction with several domain I, II, and III residues. The
      pattern of interactions suggested that C-11 was closest to domain IV, probably
      involved in a hydrogen bond with the domain IV carboxyl group. Incorporating this
      data, a new molecular model of TTX binding is proposed.

PMID- 12524283
TI  - Effect of S6 tail mutations on charge movement in Shaker potassium channels.
AB  - The cytoplasmic ends of the four S6 transmembrane segments of voltage-gated
      potassium channels converge in a bundle crossing that acts as the activation gate
      that opens in response to a depolarization. To explore whether the cytoplasmic
      extension of the S6 segment (the S6 tail) plays a role in coupling voltage sensor
      and activation gate movements, we examined the effect of cysteine substitution
      from residues N482 to T489 on the kinetics and voltage-dependence of S4 charge
      movement and on the kinetics of deactivation of ionic current. Among these
      mutants, F484C has the steepest voltage-dependent charge movement, the largest Q
      V shift, and the fastest OFF gating currents. Further study of the residue at
      position 484, using mutagenesis and modification of F484C by cysteine reagents,
      suggests that aromaticity at this position is essential to maintain normal
      coupling. We used periodicity analysis to appraise the possibility that the S6
      tail has an alpha-helical structure. Although we obtained an alpha-periodicity
      index of 2.41 for gating current parameters, a new randomization test produced an
      indecisive conclusion about the secondary structure of this region. Taken
      together, our results suggest that the tail end of S6 plays an important role in
      coupling between activation gating and charge movement.

PMID- 12524284
TI  - Hydrophilic/Hydrophobic balance determines morphology of glycolipids with
      oligolactose headgroups.
AB  - The morphology of synthetic glycolipids with lactose oligomers (Lac N, the number
      of lactose units, N = 1, 2, 3) was studied in lamellar phase. By a systematic
      combination of differential scanning calorimetry and small- and wide-angle x-ray
      scattering experiments, the effects of hydrophilic/hydrophobic balance on their
      thermotropic phase behaviors were discussed. The dispersion of Lac 1 exhibited a
      crystalline-fluid phase transition, dominated by the strong van der Waals
      interaction between dihexadecyl chains. In the case of Lac 2, the
      hydrophilic/hydrophobic balance between the headgroup and the alkyl chains is
      shifted to the hydrophilic side, resulting in a gel-fluid phase transition with a
      decreased transition temperature and phase transition enthalpy. Different from
      the first two systems, the differential scanning calorimetry trace of Lac 3
      showed much less remarkable peaks. The small- and wide-angle x-ray diffraction
      patterns did not reveal any transition in the chain ordering, suggesting that the
      correlation between the hexasaccharide headgroups is so strong that the melting
      of the alkyl chains was not allowed. Such dominant effects of the
      hydrophilic/hydrophobic balance on the morphology of Lac N lipids can be
      attributed to the small sterical mismatch between the alkyl chains and the
      linear, cylindrical oligolactose groups.

PMID- 12524285
TI  - Partitioning of ABA into bilayers of Di-saturated phosphatidylcholines as
      measured by DSC.
AB  - Using differential scanning calorimetry, we have investigated partitioning of the
      plant hormone abscisic acid into a homologous series of di-saturated
      phosphatidylcholines increasing in chain length from C(14) to C(19). Partition
      coefficients calculated from the shift in T(m) range from 1280 for DiC(14)PC to
      480 for DiC(19)PC. The free energy of transfer is chain-length independent with a
      value of DeltaG = -17.4 kJ/mol and an enthalpic contribution of DeltaH = -22.6
      kJ/mol. The low net entropic contribution of -TDeltaS = -5.2 J/mol agrees with
      the concept of the bilayer effect, but differs from that of the entropy-driven
      classic hydrophobic effect valid for partitioning between bulk solvents.
      Preferential location of the hormone in the outer region of the membrane is
      indicated by characteristic changes in the transition profiles and by comparison
      with partitioning into organic solvents whose dielectric constants model the
      interior and exterior regions of the bilayer. Differences in partitioning and
      surface pKa between the biologically active ct-ABA and the inactive tt-isomer are
      discussed for biological relevance.

PMID- 12524286
TI  - Effect of hydrophobic surfactant proteins SP-B and SP-C on binary phospholipid
      monolayers: II. Infrared external reflectance-absorption spectroscopy.
AB  - In situ external reflection infrared spectroscopy at the air-water interface was
      used to study the influence on phospholipid structure of an endogenous mixture of
      the two hydrophobic surfactant proteins, SP-B and SP-C, which are thought to play
      pivotal roles in the adsorption and function of pulmonary surfactant. Mixtures
      studied were 1:1, 2:1, and 7:1 (mol:mol) DPPC-d(62):DPPG, and 7:1 DPPC
      d(62):DOPG, alone and in the presence of 0.5-10 wt % mixed SP-B/C purified
      chromatographically from calf lung surfactant extract. Perdeuteration of DPPC
      produced a shift in vibrational frequencies so that it could be differentiated
      spectroscopically from the phosphoglycerol component in the surface monolayer.
      CH(2) antisymmetric and symmetric stretching bands ( approximately 2920 and 2852
      cm(-1)) along with the analogous CD(2) stretching bands ( approximately 2194 and
      2089 cm(-1)) were analyzed, and band heights and peak wavenumber positions were
      assessed as a function of monolayer surface pressure. Small, near-physiological
      contents of 1-2 wt % SP-B/C typically produced the maximum observed spectroscopic
      effects, which were abolished at high protein contents of 10 wt %. Analysis of
      CH(2) and CD(2) stretching bands and C-H/C-D band height ratios indicated that SP
      B/C affected PC and PG lipids differently within the surface monolayer. SP-B/C
      had preferential interactions with DPPG in 1:1, 2:1, and 7:1 DPPC-d(62):DPPG
      films that increased its acyl chain order. SP-B/C also interacted specifically
      with DOPG in 7:1 DPPC-d(62):DOPG monolayers, but in this case an increase in
      CH(2) band heights and peak wavenumber positions indicated a further disordering
      of the already fluid DOPG acyl chains. CD(2) band height and peak wavenumber
      analysis indicated that SP-B/C had no significant effect on the structure of DPPC
      d(62) chains in 7:1 films with DPPG or DOPG, and had only a slight tendency to
      increase the acyl chain order in 1:1 films of DPPC-d(62):DPPG. SP-B/C had no
      significant effect on DPPC-d(62) structure in films with DOPG. Infrared results
      also indicated that interactions involving SP-B/C and lipids led to exclusion of
      PC and PG lipids from the compressed interfacial monolayer, in agreement with our
      previous report on the phase morphology of lipid monolayers containing 1 wt % SP
      B/C.

PMID- 12524287
TI  - Unilamellar DMPC vesicles in aqueous glycerol: preferential interactions and
      thermochemistry.
AB  - Glycerol is accumulated in response to environmental stresses in a diverse range
      of organisms. Understanding of favorable in vivo effects of this solute requires
      insight into its interactions with biological macromolecules, and one access to
      this information is the quantification of so-called preferential interactions in
      glycerol-biopolymer solutions. For model membrane systems, preferential
      interactions have been discussed, but not directly measured. Hence, we have
      applied a new differential vapor pressure equipment to quantify the isoosmotic
      preferential binding parameter, Gamma( micro 1), for systems of unilamellar
      vesicles of DMPC in aqueous glycerol. It is found that Gamma( micro 1) decreases
      linearly with the glycerol concentration with a slope of -0.14 +/- 0.014 per
      molal. This implies that glycerol is preferentially excluded from the membrane
      solvent interface. Calorimetric investigations of the same systems showed that
      the glycerol-DMPC interactions are weakly endothermic, and the temperature of the
      main phase transition increases slightly (0.16 degrees C per molal) with the
      glycerol concentration. The results are discussed with respect to a molecular
      picture which takes into account both the partitioning of glycerol into the
      membrane and the preferential exclusion from the hydration layer, and it is
      concluded that the latter effect contributes about four times stronger than the
      former to the net interaction.

PMID- 12524288
TI  - Osmotic properties of poly(ethylene glycols): quantitative features of brush and
      bulk scaling laws.
AB  - From glycosylated cell surfaces to sterically stabilized liposomes, polymers
      attached to membranes attract biological and therapeutic interest. Can the
      scaling laws of polymer "brushes" describe the physical properties of these
      coats? We delineate conditions where the Alexander-de Gennes theory of polymer
      brushes successfully fits the intermembrane distance versus applied osmotic
      stress data of Kenworthy et al. for poly(ethylene glycol)-grafted multilamellar
      liposomes. We establish that the polymer density and size in the brush must be
      high enough that, in a bulk solution of equivalent monomer density, the polymer
      osmotic pressure is independent of polymer molecular weight (the des Cloizeaux
      semidilute regime of bulk polymer solutions). The condition that attached
      polymers behave as semidilute bulk solutions offers a rigorous criterion for
      brush scaling-law behavior. There is a deep connection between the behaviors of
      semidilute polymer solutions in bulk and polymers grafted to a surface at a
      density such that neighbors pack to form a uniform brush. In this regime, two
      parameter unconstrained fits of the Alexander-de Gennes brush scaling laws to the
      Kenworthy et al. data yield effective monomer lengths of 3.3-3.6 A, which agree
      with structural predictions. The fitted distances between grafting sites are
      larger than expected from the nominal mole fraction of poly(ethylene glycol)
      lipids; the chains apparently saturate the surface. Osmotic stress measurements
      can be used to estimate the actual densities of membrane-grafted polymers.

PMID- 12524289
TI  - Confined diffusion without fences of a g-protein-coupled receptor as revealed by
      single particle tracking.
AB  - Single particle tracking is a powerful tool for probing the organization and
      dynamics of the plasma membrane constituents. We used this technique to study the
      micro -opioid receptor belonging to the large family of the G-protein-coupled
      receptors involved with other partners in a signal transduction pathway. The
      specific labeling of the receptor coupled to a T7-tag at its N-terminus, stably
      expressed in fibroblastic cells, was achieved by colloidal gold coupled to a
      monoclonal anti T7-tag antibody. The lateral movements of the particles were
      followed by nanovideomicroscopy at 40 ms time resolution during 2 min with a
      spatial precision of 15 nm. The receptors were found to have either a slow or
      directed diffusion mode (10%) or a walking confined diffusion mode (90%) composed
      of a long-term random diffusion and a short-term confined diffusion, and
      corresponding to a diffusion confined within a domain that itself diffuses. The
      results indicate that the confinement is due to an effective harmonic potential
      generated by long-range attraction between the membrane proteins. A simple model
      for interacting membrane proteins diffusion is proposed that explains the
      variations with the domain size of the short-term and long-term diffusion
      coefficients.

PMID- 12524290
TI  - Sphingolipid partitioning into ordered domains in cholesterol-free and
      cholesterol-containing lipid bilayers.
AB  - We have used fluorescence-quenching measurements to characterize the partitioning
      of a variety of indolyl-labeled phospho- and sphingolipids between gel or liquid
      ordered and liquid-disordered lipid domains in several types of lipid bilayers
      where such domains coexist. In both cholesterol-free and cholesterol-containing
      lipid mixtures, sphingolipids with diverse polar headgroups (ranging from
      sphingomyelin and monoglycosylceramides to ganglioside GM1) show a net preference
      for partitioning into ordered domains, which varies modestly in magnitude with
      varying headgroup structure. The affinities of different sphingolipids for
      ordered lipid domains do not vary in a consistent manner with the size or other
      simple structural properties of the polar headgroup, such that for example
      ganglioside GM1 partitions between ordered and disordered lipid domains in a
      manner very similar to sphingomyelin. Ceramide exhibits a dramatically higher
      affinity for ordered lipid domains in both cholesterol-free and cholesterol
      containing bilayers than do other sphingolipids. Our findings suggest that
      sphingolipids with a variety of headgroup structures will be enriched by
      substantial factors in liquid-ordered versus liquid-disordered regions of
      membranes, in a manner that is only modestly dependent on the nature of the polar
      headgroup. Ceramide is predicted to show a very strong enrichment in such
      domains, supporting previous suggestions that ceramide-mediated signaling may be
      compartmentalized to liquid-ordered (raft and raft-related) domains in the plasma
      membrane.

PMID- 12524291
TI  - Hydrophobic mismatch between helices and lipid bilayers.
AB  - alpha-Helical transmembrane peptides, named WALP, with a hydrophobic sequence of
      leucine and alanine of varying length bordered at both ends by two tryptophans as
      membrane anchors, were synthesized to study the effect of hydrophobic matching in
      lipid bilayers. WALPs of 13-, 16-, and 19-residues were incorporated into 1,2
      dilauroyl-sn-glycero-3-phosphocholine (12C), 1,2-tridecanoyl-sn-glycero-3
      phosphocholine (13C), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (14C)
      bilayers in the form of oriented multilayers. Oriented circular dichroism spectra
      and x-ray diffraction patterns showed that the peptides were homogenously
      distributed in the lipid bilayers with the helical axes oriented approximately
      normal to the plane of bilayers. But in all cases, x-ray diffraction showed that
      the peptides did not alter the thickness of the bilayer. This is contrary to the
      case of gramicidin where 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2
      dilauroyl-sn-glycero-3-phosphocholine clearly thinned and thickened,
      respectively, to approach the hydrophobic thickness of the gramicidin channels.
      The result seems to indicate that the packing of lipid chains around a single
      helix is fundamentally different from the way the chains pack against a large
      protein surface.

PMID- 12524292
TI  - Binding of a fluorescent lipid amphiphile to albumin and its transfer to lipid
      bilayer membranes.
AB  - Kinetics and thermodynamics of the binding of a fluorescent lipid amphiphile,
      Rhodamine Green(TM)-tetradecylamide (RG-C(14:0)), to bovine serum albumin were
      characterized in an equilibrium titration and by stopped-flow fluorimetry. The
      binding equilibrium of RG-C(14:0) to albumin was then used to reduce its
      concentration in the aqueous phase to a value below its critical micelle
      concentration. Under these conditions, the only two species of RG-C(14:0) in the
      system were the monomer in aqueous solution in equilibrium with the protein-bound
      species. After previous determination of the kinetic and thermodynamic parameters
      for association of RG-C(14:0) with albumin, the kinetics of insertion of the
      amphiphile into and desorption off lipid bilayer membranes in different phases
      (solid, liquid-ordered, and liquid-disordered phases, presented as large
      unilamellar vesicles) were studied by stopped-flow fluorimetry at 30 degrees C.
      Insertion and desorption rate constants for association of the RG-C(14:0) monomer
      with the lipid bilayers were used to obtain lipid/water equilibrium partition
      coefficients for this fluorescent amphiphile. The direct measurement of these
      partition coefficients is shown to provide a new method for the indirect
      determination of the equilibrium partition coefficient of similar molecules
      between two defined lipid phases if they coexist in the same membrane.

PMID- 12524293
TI  - Lowering the barriers to random walks on the cell surface.
AB  - We used fluorescence recovery after photobleaching (FRAP) and single particle
      tracking (SPT) techniques to compare diffusion of class I major
      histocompatibility complex molecules (MHC) on normal and alpha-spectrin-deficient
      murine erythroleukemia (MEL) cells. Because the cytoskeleton mesh acts as a
      barrier to lateral mobility of membrane proteins, we expected that diffusion of
      membrane proteins in alpha-spectrin-deficient MEL cells would differ greatly from
      that in normal MEL cells. In the event, diffusion coefficients derived from
      either FRAP or SPT analysis were similar for alpha-spectrin-deficient and normal
      MEL cells, differing by a factor of approximately 2, on three different
      timescales: tens of seconds, 1-10 s, and 100 ms. SPT analysis showed that the
      diffusion of most class I MHC molecules was confined on both cell types. On the
      normal MEL cells, the mean diagonal length of the confined area was 330 nm with a
      mean residency time of 40s. On the alpha-spectrin-deficient MEL cells, the mean
      diagonal length was 650 nm with a mean residency time of 45s. Thus there are
      fewer barriers to lateral diffusion on cytoskeleton mutant MEL cells than on
      normal MEL cells, but this difference does not strongly affect lateral diffusion
      on the scales measured here.

PMID- 12524294
TI  - Measuring distances in supported bilayers by fluorescence interference-contrast
      microscopy: polymer supports and SNARE proteins.
AB  - Fluorescence interference-contrast (FLIC) microscopy is a powerful new technique
      to measure vertical distances from reflective surfaces. A pattern of varying
      intensity is created by constructive and destructive interference of the incoming
      and reflected light at the surface of an oxidized silicon chip. Different levels
      of this pattern are probed by manufacturing silicon chips with terraces of oxide
      layers of different heights. Fluorescence collected from membranes that are
      deposited on these terraces is then used to measure the distance of the
      fluorescent probes from the silicon oxide surface. Here, we applied the method to
      measure the distance between supported lipid bilayers and the surface of oxidized
      silicon chips. For plain fluid phosphatidylcholine bilayers, this distance was
      1.7 +/- 1.0 nm. The cleft distance was increased to 3.9 +/- 0.9 nm in bilayers
      that were supported on a 3400-Da polyethylene glycol cushion. This distance is
      close to the Flory distance (4.8 nm) that would be expected for a grafted random
      coil of this polymer. In a second application, the distance of a membrane-bound
      protein from the membrane surface was measured. The integral membrane protein
      syntaxin1A/SNAP25 (t-SNARE) was reconstituted into tethered polymer-supported
      bilayers. A soluble form of the green fluorescent protein/vesicle-associated
      membrane protein (GFP-VAMP) was bound to the reconstituted t-SNAREs. The distance
      of the GFP from the membrane surface was 16.5 +/- 2.8 nm, indicating an upright
      orientation of the rod-shaped t-SNARE/v-SNARE complex from the membrane surface.

PMID- 12524295
TI  - Sequence-dependent DNA condensation and the electrostatic zipper.
AB  - Sequence-dependent configuration changes and condensation of double-stranded
      poly(dG-dC).(dG-dC) (GC-DNA) and ds poly(dA-dT).(dA-dT) (AT-DNA) were observed by
      atomic force microscopy in the presence of Ni(II). Less condensing agent was
      required to generate configuration changes in GC-DNA as compared to AT-DNA. In
      the presence of Ni(II) cations, GC-DNA adopted a Z-type conformation and
      underwent a stepwise condensation, starting with partial intramolecular folding,
      followed by intermolecular condensation of two to several molecules and ending
      with the formation of toroids, rods, and jumbles. GC-DNA condensates were unusual
      in that the most highly condensed regions were surrounded by loops of ds GC-DNA.
      In contrast, AT-DNA retained its B-type conformation and displayed only minor
      condensation even at high Ni(II) concentrations. The Ni(II)-dependent differences
      in condensation between GC-DNA and AT-DNA are predicted by an extension of the
      electrostatic zipper motif proposed by Kornyshev and Leikin, in which we account
      for shorter than Debye screening length surface separations between the DNA
      molecules and for the Ni(II)-induced conformation change of GC-DNA to Z-DNA.

PMID- 12524296
TI  - Binding of actinomycin D to single-stranded DNA of sequence motifs d(TGTCT(n)G)
      and d(TGT(n)GTCT).
AB  - Our recent binding studies with oligomers derived from base replacements on
      d(CGTCGTCG) had led to the finding that actinomycin D (ACTD) binds strongly to
      d(TGTCATTG) of apparent single-stranded conformation without GpC sequence. A fold
      back binding model was speculated in which the planar phenoxazone inserts at the
      GTC site with a loop-out T base whereas the G base at the 3'-terminus folds back
      to form a basepair with the internal C and stacks on the opposite face of the
      chromophore. To provide a more concrete support for such a model, ACTD
      equilibrium binding studies were carried out and the results are reported herein
      on oligomers of sequence motifs d(TGTCT(n)G) and d(TGT(n)GTC). These oligomers
      are not expected to form dimeric duplexes and contain no canonical GpC sequences.
      It was found that ACTD binds strongly to d(TGTCTTTTG), d(TGTTTTGTC), and
      d(TGTTTTTGTC), all exhibiting 1:1 drug/strand binding stoichiometry. The fold
      back binding model with displaced T base is further supported by the finding that
      appending TC and TCA at the 3'-terminus of d(TGTCTTTTG) results in oligomers that
      exhibit enhanced ACTD affinities, consequence of the added basepairing to
      facilitate the hairpin formation of d(TGTCTTTTGTC) and d(TGTCTTTTGTCA) in
      stabilizing the GTC/GTC binding site for juxtaposing the two G bases for easy
      stacking on both faces of the phenoxazone chromophore. Further support comes from
      the observation of considerable reduction in ACTD affinity when GTC is replaced
      by GTTC in an oligomer, in line with the reasoning that displacing two T bases to
      form a bulge for ACTD binding is more difficult than displacing a single base.
      Based on the elucidated binding principle of phenoxazone ring requiring its
      opposite faces to be stacked by the 3'-sides of two G bases for tight ACTD
      binding, several oligonucleotide sequences have been designed and found to bind
      well.

PMID- 12524297
TI  - Low-intensity pump-probe measurements on the B800 band of Rhodospirillum
      molischianum.
AB  - We have measured low-intensity, polarized one-color pump-probe traces in the B800
      band of the light-harvesting complex LH2 of Rhodospirillum molischianum at 77 K.
      The excitation/detection wavelength was tuned through the B800 band. A single
      wavelength and a global target analysis of the data were performed with a model
      that accounts for excitation energy transfer among the B800 molecules and from
      B800 to B850. By including the anisotropy of the signals into the fitting
      procedure, both transfer processes could be separated. It was estimated in the
      global target analysis that the intra-B800 energy transfer, i.e., the hopping of
      the excitation from one B800 to another B800 molecule, takes approximately 0.5 ps
      at 77 K. This transfer time increases with the excitation/detection wavelength
      from 0.3 ps on the blue side of the B800 band to approximately 0.8 ps on the red
      side. The residual B800 anisotropy shows a wavelength dependence as expected for
      energy transfer within an inhomogeneously broadened cluster of weakly coupled
      pigments. In the global target analysis, the transfer time from B800 to B850 was
      determined to be approximately 1.7 ps at 77 K. In the single-wavelength analysis,
      a speeding-up of the B800 --> B850 energy transfer rate toward the blue edge of
      the B800 band was found. This nicely correlates with the proposed position of the
      suggested high-exciton component of the B850 band acting as an additional decay
      channel for B800 excitations.

PMID- 12524298
TI  - Energy transfer in light-harvesting complexes LHCII and CP29 of spinach studied
      with three pulse echo peak shift and transient grating.
AB  - Three pulse echo peak shift and transient grating (TG) measurements on the plant
      light-harvesting complexes LHCII and CP29 are reported. The LHCII complex is by
      far the most abundant light-harvesting complex in higher plants and fulfills
      several important physiological functions such as light-harvesting and
      photoprotection. Our study is focused on the light-harvesting function of LHCII
      and the very similar CP29 complex and reveals hitherto unresolved excitation
      energy transfer processes. All measurements were performed at room temperature
      using detergent isolated complexes from spinach leaves. Both complexes were
      excited in their Chl b band at 650 nm and in the blue shoulder of the Chl a band
      at 670 nm. Exponential fits to the TG and three pulse echo peak shift decay
      curves were used to estimate the timescales of the observed energy transfer
      processes. At 650 nm, the TG decay can be described with time constants of 130 fs
      and 2.2 ps for CP29, and 300 fs and 2.8 ps for LHCII. At 670 nm, the TG shows
      decay components of 230 fs and 6 ps for LHCII, and 300 fs and 5 ps for CP29.
      These time constants correspond to well-known energy transfer processes, from Chl
      b to Chl a for the 650 nm TG and from blue (670 nm) Chl a to red (680 nm) Chl a
      for the 670 nm TG. The peak shift decay times are entirely different. At 650 nm
      we find times of 150 fs and 0.5-1 ps for LHCII, and 360 fs and 3 ps for CP29,
      which we can associate mainly with Chl b <--> Chl b energy transfer. At 670 nm we
      find times of 140 fs and 3 ps for LHCII, and 3 ps for CP29, which we can
      associate with fast (only in LHCII) and slow transfer between relatively blue
      Chls a or Chl a states. From the occurrence of both fast Chl b <--> Chl b and
      fast Chl b --> Chl a transfer in CP29, we conclude that at least two mixed
      binding sites are present in this complex. A detailed comparison of our observed
      rates with exciton calculations on both CP29 and LHCII provides us with more
      insight in the location of these mixed sites. Most importantly, for CP29, we find
      that a Chl b pair must be present in some, but not all, complexes, on sites A(3)
      and B(3). For LHCII, the observed rates can best be understood if the same pair,
      A(3) and B(3), is involved in both fast Chl b <--> Chl b and fast Chl a <--> Chl
      a transfer. Hence, it is likely that mixed sites also occur in the native LHCII
      complex. Such flexibility in chlorophyll binding would agree with the general
      flexibility in aggregation form and xanthophyll binding of the LHCII complex and
      could be of use for optimizing the role of LHCII under specific circumstances,
      for example under high-light conditions. Our study is the first to provide
      spectroscopic evidence for mixed binding sites, as well as the first to show
      their existence in native complexes.

PMID- 12524299
TI  - Vibrational spectroscopy of an algal Phot-LOV1 domain probes the molecular
      changes associated with blue-light reception.
AB  - The LOV1 domain of the blue light Phot1-receptor (phototropin homolog) from
      Chlamydomonas reinhardtii has been studied by vibrational spectroscopy. The FMN
      modes of the dark state of LOV1 were identified by preresonance Raman
      spectroscopy and assigned to molecular vibrations. By comparing the blue-light
      induced FTIR difference spectrum with the preresonance Raman spectrum, most of
      the differences are due to FMN modes. Thus, we exclude large backbone changes of
      the protein that might occur during the phototransformation of the dark state
      LOV1-447 into the putative signaling state LOV1-390. Still, the presence of
      smaller amide difference bands cannot be excluded but may be masked by
      overlapping FMN modes. The band at 2567 cm(-1) is assigned to the S-H stretching
      vibration of C57, the residue that forms the transient thio-adduct with the
      chromophore FMN. The occurrence of this band is evidence that C57 is protonated
      in the dark state of LOV1. This result challenges conclusions from the homologous
      LOV2 domain from oat that the thiolate of the corresponding cysteine is the
      reactive species.

PMID- 12524300
TI  - Universality classes in folding times of proteins.
AB  - Molecular dynamics simulations in simplified models allow one to study the
      scaling properties of folding times for many proteins together under a controlled
      setting. We consider three variants of the Go models with different contact
      potentials and demonstrate scaling described by power laws and no correlation
      with the relative contact order parameter. We demonstrate existence of at least
      three kinetic universality classes that are correlated with the types of
      structure: the alpha-, alpha-beta-, and beta- proteins have the scaling exponents
      of approximately 1.7, 2.5, and 3.2, respectively. The three classes merge into
      one when the contact range is truncated at a reasonable value. We elucidate the
      role of the potential associated with the chirality of a protein.

PMID- 12524301
TI  - 19 A solution structure of the filarial nematode immunomodulatory protein, ES-62.
AB  - ES-62, a protein secreted by filarial nematodes, parasites of vertebrates
      including humans, has an unusual posttranslational covalent addition of
      phosphorylcholine to an N-type glycan. Studies on ES-62 from the rodent parasite
      Acanthocheilonema viteae ascribe it a dominant role in ensuring parasite survival
      by modulating the host immune system. Understanding this immunomodulation at the
      molecular level awaits full elucidation but distinct components of ES-62 may
      participate: the protein contributes aminopeptidase-like activity whereas the
      phosphorylcholine is thought to act as a signal transducer. We have used
      biophysical and bioinformatics-based structure prediction methods to define a low
      resolution model of ES-62. Sedimentation equilibrium showed that ES-62 is a
      tightly bound tetramer. The sedimentation coefficient is consistent with this
      oligomer and the overall molecular shape revealed by small angle x-ray
      scattering. A 19 A model for ES-62 was restored from the small-angle x-ray
      scattering data using the program DAMMIN which uses simulated annealing to find a
      configuration of densely packed scattering elements consistent with the
      experimental scattering curve. Analysis of the primary sequence with the position
      specific iterated basic local alignment search tool, PSI-BLAST, identified six
      closely homologous proteins, five of which are peptidases, consistent with
      observed aminopeptidase activity in ES-62. Differences between the secondary
      structure content of ES-62 predicted using the consensus output from the
      secondary structure prediction server JPRED and measured using circular dichroism
      are discussed in relation to multimeric glycosylated proteins. This study
      represents the first attempt to understand the multifunctional properties of this
      important parasite-derived molecule by studying its structure.

PMID- 12524302
TI  - Fluorescence determination of tryptophan side-chain accessibility and dynamics in
      triple-helical collagen-like peptides.
AB  - We report tryptophan fluorescence measurements of emission intensity, iodide
      quenching, and anisotropy that describe the environment and dynamics at X and Y
      sites in stable collagen-like peptides of sequence (Gly-X-Y)(n). About 90% of
      tryptophans at both sites have similar solvent exposed fluorescence properties
      and a lifetime of 8.5-9 ns. Analysis of anisotropy decays using an associative
      model indicates that these long lifetime populations undergo rapid depolarizing
      motion with a 0.5 ns correlation time; however, the extent of fast motion at the
      Y site is considerably less than the essentially unrestricted motion at the X
      site. About 10% of tryptophans at both sites have a shorter ( approximately 3 ns)
      lifetime indicating proximity to a protein quenching group; these minor
      populations are immobile on the peptide surface, depolarizing only by overall
      trimer rotation. Iodide quenching indicates that tryptophans at the X site are
      more accessible to solvent. Side chains at X sites are more solvent accessible
      and considerably more mobile than residues at Y sites and can more readily
      fluctuate among alternate intermolecular interactions in collagen fibrils. This
      fluorescence analysis of collagen-like peptides lays a foundation for studies on
      the structure, dynamics, and function of collagen and of triple-helical junctions
      in gelatin gels.

PMID- 12524303
TI  - Study of binding between protein A and immunoglobulin G using a surface tension
      probe.
AB  - Molecular interactions and binding are one of the most important and fundamental
      properties in the study of biochemical and biomedical systems. The understanding
      of such interactions and binding among biomolecules forms the basis for the
      design and processing of many biotechnological applications, such as
      bioseparation and immunoadsorption. In this study, we present a novel method to
      probe molecular interactions and binding based on surface tension measurement.
      This method complements conventional techniques, which are largely based on
      optical, spectroscopic, fluorescence polarization, chromatographic or atomic
      force microscopy measurements, by being definite in determining molecular binding
      ratio and flexible in sample preparation. Both dynamic and equilibrium (or quasi
      equilibrium) information on molecular binding can be obtained through dynamic and
      equilibrium surface tension measurements. For an important pair of biological
      ligand and ligate, Protein A and immunoglobulin G (IgG), the existence of
      molecular interactions and the binding ratio of 1:2 have been determined
      unequivocally with the proposed surface tension method. These results are
      confirmed/supported by a mass balance calculation and spectrophotometry
      experiment. In addition, adsorption isotherms for Protein A and IgG separately at
      the air/water interface have been established with the dynamic surface tension
      measurements. The results show that the Langmuir isotherm equation can describe
      the adsorption data satisfactorily for both Protein A and IgG solutions.

PMID- 12524304
TI  - Protein interactions in undersaturated and supersaturated solutions: a study
      using light and x-ray scattering.
AB  - Protein interactions in undersaturated and supersaturated solutions were
      investigated using static and dynamic light scattering and small angle x-ray
      scattering. A morphodrom of lysozyme crystals determined at 35 degrees C and pH =
      4.6 was used as a guideline in selecting the protein and precipitant
      concentrations. The osmotic second virial coefficient, B(22), was determined by
      static and dynamic light scattering. At low ionic strengths for which no crystals
      were formed, B(22) was positive indicating repulsive interactions between the
      protein molecules. Negative B(22) at higher ionic strengths corresponds to
      attractive interactions where crystallization becomes possible. At two extreme
      salt concentrations, small angle x-ray scattering data were collected and fitted
      with a statistical mechanical model based on Derjaguin-Landau-Verwey-Overbeek
      potential using Random Phase Approximation. This model accounted well for the
      small angle x-ray scattering data at undersaturated condition with constant
      potential parameters. At very high salt concentration corresponding to
      supersaturated solution this model seems to fail, possibly due to the presence of
      non-Derjaguin-Landau-Verwey-Overbeek hydration repulsion between the molecules.

PMID- 12524305
TI  - Cooperativity in forced unfolding of tandem spectrin repeats.
AB  - Force-driven conformational changes provide a broad basis for protein
      extensibility, and multidomain proteins broaden the possibilities further by
      allowing for a multiplicity of forcibly extended states. Red cell spectrin is
      prototypical in being an extensible, multidomain protein widely recognized for
      its contribution to erythrocyte flexibility. Atomic force microscopy has already
      shown that single repeats of various spectrin family proteins can be forced to
      unfold reversibly under extension. Recent structural data indicates, however,
      that the linker between triple-helical spectrin repeats is often a contiguous
      helix, thus raising questions as to what the linker contributes and what defines
      a domain mechanically. We have examined the extensible unfolding of red cell
      spectrins as monomeric constructs of just two, three, or four repeats from the
      actin-binding ends of both alpha- and beta-chains, i.e., alpha(18-21) and beta(1
      4) or their subfragments. In addition to single repeat unfolding evident in
      sawtooth patterns peaked at relatively low forces (<50 pN at 1 nm/ms extension
      rates), tandem repeat unfolding is also demonstrated in ensemble-scale analyses
      of thousands of atomic force microscopy contacts. Evidence for extending two
      chains and loops is provided by force versus length scatterplots which also
      indicate that tandem repeat unfolding occurs at a significant frequency relative
      to single repeat unfolding. Cooperativity in forced unfolding of spectrin is also
      clearly demonstrated by a common force scale for the unfolding of both single and
      tandem repeats.

PMID- 12524306
TI  - Application of NMRD to hydration of rubredoxin and a variant containing a (Cys
      S)3FeIII(OH) site.
AB  - Hydration of oxidized rubredoxin (Fe(III)(S-Cys)(4) center) was investigated by
      (1)H and (17)O relaxation measurements of bulk water as a function of the applied
      magnetic field (nuclear magnetic relaxation dispersion). Oxidized rubredoxin
      showed an increased water (1)H relaxation profile with respect to the diamagnetic
      gallium derivative or reduced species. Analysis of the data shows evidence of
      exchangeable proton(s) approximately 4.0-4.5 A from the metal ion, the exchange
      time being longer than 10(-10) s and shorter than 10(-5) s. The correlation time
      for the proton-electrons interaction is 7 x 10(-11) s and is attributed to the
      effective electron relaxation time. Its magnitude is consistent with the large
      signal linewidths of the protein donor nuclei, observed in high resolution NMR
      spectra. For reduced rubredoxin, such correlation time is proposed to be smaller
      than 10(-11) s. (17)O relaxation measurements suggest the presence of at least
      one long-lived protein-bound water molecule. Analogous relaxation measurements
      were performed on the C6S rubredoxin variant, whose iron(III) center has been
      previously shown to be coordinated to three cysteine residues and a hydroxide ion
      above pH 6. (1)H nuclear magnetic relaxation dispersion profiles indicate
      increased hydration with respect to the wild-type.

PMID- 12524307
TI  - Freezing of a fish antifreeze protein results in amyloid fibril formation.
AB  - Amyloid is associated with a number of diseases including Alzheimer's,
      Huntington's, Parkinson's, and the spongiform encephalopathies. Amyloid fibrils
      have been formed in vitro from both disease and nondisease related proteins, but
      the latter requires extremes of pH, heat, or the presence of a chaotropic agent.
      We show, using fluorescence spectroscopy, electron microscopy, and solid-state
      NMR spectroscopy, that the alpha-helical type I antifreeze protein from the
      winter flounder forms amyloid fibrils at pH 4 and 7 upon freezing and thawing.
      Our results demonstrate that the freezing of some proteins may accelerate the
      formation of amyloid fibrils.

PMID- 12524308
TI  - Protein reorientation and bound water molecules measured by 1H magnetic spin
      lattice relaxation.
AB  - The water-proton spin-lattice relaxation rate constant, 1/T(1), was measured as a
      function of magnetic field strength for several dilute protein solutions. By
      separating the intermolecular contributions from the intramolecular contributions
      to the water-proton spin-lattice relaxation, the number of water molecules that
      bind to the protein for a time long compared with the rotational correlation time
      may be measured. We find a good correlation between the number of long-lived
      water molecules and the predictions based on available free volume in the
      proteins studied. The rotational correlation times of these proteins are larger
      than predicted by the Stokes-Einstein-Debye (SED) model for a sphere reorienting
      in a viscous liquid. The discrepancy between experiment and theory is usually
      attributed to hydration effects increasing the effective radius of the particle.
      However, the average lifetime of water molecules at the protein interface is far
      too short to justify such a picture. We suggest that surface roughness may be
      responsible for the retardation of rotational mobility and find that the SED
      model provides a reasonable representation of experiment if the radius assumed
      for the reorienting particle is the arithmetic mean of the crystallographic
      packing radius and the radius deduced from the effective surface area of the
      protein.

PMID- 12524309
TI  - The role of hydration on the mechanism of allosteric regulation: in situ
      measurements of the oxygen-linked kinetics of water binding to hemoglobin.
AB  - We report here the first direct measurements of changes in protein hydration
      triggered by a functional binding. This task is achieved by weighing hemoglobin
      (Hb) and myoglobin films exposed to an atmosphere of 98% relative humidity during
      oxygenation. The binding of the first oxygen molecules to Hb tetramer triggers a
      change in protein conformation, which increases binding affinity to the remaining
      empty sites giving rise to the appearance of cooperative phenomena. Although
      crystallographic data have evidenced that this structural change increases the
      protein water-accessible surface area, isobaric osmotic stress experiments in
      aqueous cosolutions have shown that water binding is linked to Hb oxygenation.
      Now we show that the differential hydration between fully oxygenated and fully
      deoxygenated states of these proteins, determined by weighing protein films with
      a quartz crystal microbalance, agree with the ones determined by osmotic stress
      in aqueous cosolutions, from the linkage between protein oxygen affinity and
      water activity. The agreements prove that the changes in water activity brought
      about by adding osmolytes to the buffer solution shift biochemical equilibrium in
      proportion to the number of water molecules associated with the reaction. The
      concomitant kinetics of oxygen and of water binding to Hb have been also
      determined. The data show that the binding of water molecules to the extra
      protein surface exposed on the transition from the low-affinity T to the high
      affinity R conformations of hemoglobin is the rate-limiting step of Hb
      cooperative reaction. This evidences that water binding is a crucial step on the
      allosteric mechanism regulating cooperative interactions, and suggests the
      possibility that environmental water activity might be engaged in the kinetic
      control of some important reactions in vivo.

PMID- 12524310
TI  - Variable symmetry in Salmonella typhimurium flagellar motors.
AB  - Electron cryomicroscopy of rotor complexes of the Salmonella typhimurium
      flagellar motor, overproduced in a nonmotile Escherichia coli host, has revealed
      a variation in subunit symmetry of the cytoplasmic ring (C ring) module. C rings
      with subunit symmetries ranging from 31 to 38 were found. They formed a Gaussian
      distribution around a mean between 34 and 35, a similar number to that determined
      for native C rings. C-ring diameter scaled with the number of subunits,
      indicating that the elliptical-shaped subunits maintained constant intersubunit
      spacing. Taken together with evidence that the M ring does not correspondingly
      increase in size, this finding indicates that rotor assembly does not require
      strict stoichiometric interactions between the M- and C-ring subunits.
      Implications for motor function are discussed.

PMID- 12524311
TI  - Surface charge density determines the efficiency of cationic gemini surfactant
      based lipofection.
AB  - The efficiencies of the binary liposomes composed of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine and cationic gemini surfactant, (2S,3R)-2,3-dimethoxy-1,4-bis(N
      hexadecyl-N,N-dimethylammonium)butane dibromide as transfection vectors, were
      measured using the enhanced green fluorescent protein coding plasmid and COS-1
      cells. Strong correlation between the transfection efficiency and lipid
      stoichiometry was observed. Accordingly, liposomes with X(SR-1) > or = 0.50
      conveyed the enhanced green fluorescent protein coding plasmid effectively into
      cells. The condensation of DNA by liposomes with X(SR-1) > 0.50 was indicated by
      static light scattering and ethidium bromide intercalation assay, whereas
      differential scanning calorimetry and fluorescence anisotropy of
      diphenylhexatriene revealed stoichiometry dependent reorganization in the
      headgroup region of the liposome bilayer, in alignment with our previous Langmuir
      balance study. Surface charge density and the organization of positive charges
      appear to determine the mode of interaction of DNA with (2S,3R)-2,3-dimethoxy-1,4
      bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide/1,2-dimyristoyl-sn-glycero
      3-phosphocholine liposomes, only resulting in DNA condensation when X(SR-1) >
      0.50. Condensation of DNA in turn seems to be required for efficient
      transfection.

PMID- 12524312
TI  - Two-photon thermal bleaching of single fluorescent molecules.
AB  - We have studied the fluorescence emission by two-photon excitation of four dyes
      widely used for bioimaging studies, rhodamine 6G, fluorescein, pyrene and indo-1
      at the single molecule level. The single dye molecules, spread on a glass
      substrate by spin coating, show a constant fluorescence output until a sudden
      transition to a dark state very close to the background. The bleaching time that
      is found to vary in the series pyrene, indo-1, fluorescein and rhodamine 6G from
      the fastest to the slowest one respectively, has a Gaussian distribution
      indicating that the observed behavior is not due to photobleaching. Moreover, the
      bleaching time decreases with the glass substrate temperature reaching a
      vanishing nonmeasurable value for a limiting temperature whose value is found in
      the same series as for the bleaching time, from the lowest to the highest
      temperature respectively. The observed bleaching shows a clear correlation to the
      amount of absorbed power not reirradiated as fluorescence and to the complexity
      of the molecule. These observations are interpreted as thermal bleaching where
      the temperature increase is induced by the two-photon absorption of the single
      dyes as confirmed also by numerical simulations.

PMID- 12524313
TI  - Constrained analysis of fluorescence anisotropy decay:application to experimental
      protein dynamics.
AB  - Hydrodynamic properties as well as structural dynamics of proteins can be
      investigated by the well-established experimental method of fluorescence
      anisotropy decay. Successful use of this method depends on determination of the
      correct kinetic model, the extent of cross-correlation between parameters in the
      fitting function, and differences between the timescales of the depolarizing
      motions and the fluorophore's fluorescence lifetime. We have tested the utility
      of an independently measured steady-state anisotropy value as a constraint during
      data analysis to reduce parameter cross correlation and to increase the
      timescales over which anisotropy decay parameters can be recovered accurately for
      two calcium-binding proteins. Mutant rat F102W parvalbumin was used as a model
      system because its single tryptophan residue exhibits monoexponential
      fluorescence intensity and anisotropy decay kinetics. Cod parvalbumin, a protein
      with a single tryptophan residue that exhibits multiexponential fluorescence
      decay kinetics, was also examined as a more complex model. Anisotropy decays were
      measured for both proteins as a function of solution viscosity to vary
      hydrodynamic parameters. The use of the steady-state anisotropy as a constraint
      significantly improved the precision and accuracy of recovered parameters for
      both proteins, particularly for viscosities at which the protein's rotational
      correlation time was much longer than the fluorescence lifetime. Thus, basic
      hydrodynamic properties of larger biomolecules can now be determined with more
      precision and accuracy by fluorescence anisotropy decay.

PMID- 12524314
TI  - Simultaneous optical and electrical recording of single gramicidin channels.
AB  - We report here an approach for simultaneous fluorescence imaging and electrical
      recording of single ion channels in planar bilayer membranes. As a test case,
      fluorescently labeled (Cy3 and Cy5) gramicidin derivatives were imaged at the
      single-molecule level using far-field illumination and cooled CCD camera
      detection. Gramicidin monomers were observed to diffuse in the plane of the
      membrane with a diffusion coefficient of 3.3 x 10(-8) cm(2)s(-1). Simultaneous
      electrical recording detected gramicidin homodimer (Cy3/Cy3, Cy5/Cy5) and
      heterodimer (Cy3/Cy5) channels. Heterodimer formation was observed optically by
      the appearance of a fluorescence resonance energy transfer (FRET) signal
      (irradiation of Cy3, detection of Cy5). The number of FRET signals was
      significantly smaller than the number of Cy3 signals (Cy3 monomers plus Cy3
      homodimers) as expected. The number of FRET signals increased with increasing
      channel activity. In numerous cases the appearance of a FRET signal was observed
      to correlate with a channel opening event detected electrically. The heterodimers
      also diffused in the plane of the membrane with a diffusion coefficient of 3.0 x
      10(-8) cm(2)s(-1). These experiments demonstrate the feasibility of simultaneous
      optical and electrical detection of structural changes in single ion channels as
      well as suggesting strategies for improving the reliability of such measurements.

PMID- 12524315
TI  - Parallel microchannel-based measurements of individual erythrocyte areas and
      volumes.
AB  - We describe a microchannel device which utilizes a novel approach to obtain area
      and volume measurements on many individual red blood cells. Red cells are
      aspirated into the microchannels much as a single red blood cell is aspirated
      into a micropipette. Inasmuch as there are thousands of identical microchannels
      with defined geometry, data for many individual red cells can be rapidly
      acquired, and the fundamental heterogeneity of cell membrane biophysics can be
      analyzed. Fluorescent labels can be used to quantify red cell surface and
      cytosolic features of interest simultaneously with the measurement of area and
      volume for a given cell. Experiments that demonstrate and evaluate the
      microchannel measuring capabilities are presented and potential improvements and
      extensions are discussed.

PMID- 12524316
TI  - The 2'-O- and 3'-O-Cy3-EDA-ATP(ADP) complexes with myosin subfragment-1 are
      spectroscopically distinct.
AB  - Ribose-modified highly-fluorescent sulfoindocyanine ATP and ADP analogs, 2'(3')-O
      Cy3-EDA-AT(D)P, with kinetics similar to AT(D)P, enable myosin and actomyosin
      ATPase enzymology with single substrate molecules. Stopped-flow studies recording
      both fluorescence and anisotropy during binding to skeletal muscle myosin
      subfragment-1 (S1) and subsequent single-turnover decay of steady-state
      intermediates showed that on complex formation, 2'-O- isomer fluorescence
      quenched by 5%, anisotropy increased from 0.208 to 0.357, and then decayed with
      turnover rate k(cat) 0.07 s(-1); however, 3'-O- isomer fluorescence increased
      77%, and anisotropy from 0.202 to 0.389, but k(cat) was 0.03 s(-1). Cy3-EDA
      ADP.S1 complexes with vanadate (V(i)) were studied kinetically and by time
      resolved fluorometry as stable analogs of the steady-state intermediates. Upon
      formation of the 3'-O-Cy3-EDA-ADP.S1.V(i) complex fluorescence doubled and
      anisotropy increased to 0.372; for the 2'-O- isomer, anisotropy increased to
      0.343 but fluorescence only 6%. Average fluorescent lifetimes of 2'-O- and 3'-O
      Cy3-EDA-ADP.S1.V(i) complexes, 0.9 and 1.85 ns, compare with approximately 0.7 ns
      for free analogs. Dynamic polarization shows rotational correlation times higher
      than 100 ns for both Cy3-EDA-ADP.S1.V(i) complexes, but the 2'-O-isomer only has
      also a 0.2-ns component. Thus, when bound, 3'-O-Cy3-EDA-ADP's fluorescence is
      twofold brighter with motion more restricted and turnover slower than the 2'-O
      isomer; these data are relevant for applications of these analogs in single
      molecule studies.

PMID- 12524317
TI  - Excitonic heterodimer formation in an HIV-1 oligonucleotide labeled with a donor
      acceptor pair used for fluorescence resonance energy transfer.
AB  - In this study, we investigated the absorbance and fluorescence properties of
      cTAR, the complementary DNA sequence of the transactivation response element of
      the HIV-1 genome, doubly end-labeled by different dyes, 5(and 6)
      carboxyfluorescein (Fl) and 5(and 6)-carboxytetramethylrhodamine (TMR),
      frequently used in fluorescence resonance energy transfer (FRET) studies. This
      oligonucleotide forms a stable stem-loop structure. The absorption spectrum of
      this species clearly differed from that of a doubly labeled cTAR derivative in
      which the terminal part of the stem is melted and from an equimolecular mixture
      of singly labeled species. Moreover, no significant TMR fluorescence change
      accompanies the dramatic Fl intensity increase when the doubly labeled native
      cTAR was melted by temperature or annealed with its complementary sequence. Both
      elements suggest the formation of an H-type ground-state heterodimer between Fl
      and TMR that may be described by the molecular exciton model. Moreover, time
      resolved fluorescence further suggests that the nonfluorescent heterodimer is in
      equilibrium with a small population of partially melted species showing FRET.
      Based on the spectral shifts associated with heterodimer formation, an
      interchromophore distance of 7.7 A was calculated. Both the excitonic signal and
      the Fl fluorescence were used as sensitive tools to monitor the temperature
      mediated and HIV nucleocapsid protein-mediated annealing of cTAR with its
      complementary sequence.

PMID- 12524318
TI  - Solution structure of the tachykinin peptide eledoisin.
AB  - Both the aqueous and the lipid-induced structure of eledoisin, an undecapeptide
      of mollusk origin, have been studied by two-dimensional proton nuclear magnetic
      resonance spectroscopy and distance geometry calculations. Unambiguous nuclear
      magnetic resonance assignments of protons have been made with the aid of
      correlation spectroscopy experiments and nuclear Overhauser effect spectroscopy
      experiments. The distance constraints obtained from the nuclear magnetic
      resonance data have been utilized in a distance geometry algorithm to generate a
      family of structures, which have been refined using restrained energy
      minimization and dynamics. These data show that, while in water and dimethyl
      sulfoxide, eledoisin prefers to be in an extended chain conformation, whereas in
      the presence of perdeuterated dodecylphosphocholine micelles, a membrane model
      system, helical conformation is induced in the central core and C-terminal region
      (K4-M11) of the peptide. N terminus, though less defined, also displays some
      degree of order and a possible turn structure. The conformation adopted by
      eledoisin in the presence of dodecylphosphocholine micelles is similar to the
      structural motif typical of neurokinin-2 selective agonists and with that
      reported for kassinin in hydrophobic environment.

PMID- 12524319
TI  - Modulation of nuclear pore topology by transport modifiers.
AB  - The nuclear pore complex (NPC) represents the only pathway for macromolecular
      communication between the nuclear and cytoplasmic compartments of the cell.
      Nucleocytoplasmic transport requires the interaction of transport receptors with
      phenylalanine-glycine (FG)-repeats that line the transport pathway through the
      NPC. Here we examine the effects of transport receptors and amphipathic alcohols
      on NPC topology using scanning force microscopy. We show that transport receptors
      that irreversibly bind FG-repeats increase NPC vertical aspect, whereas transport
      receptors that weakly interact with FG-repeats increase NPC diameter.
      Interestingly, small polar alcohols likewise increase NPC diameter. These
      opposing effects agree with the inhibition or enhancement of nuclear transport,
      respectively, previously ascribed to these agents.

PMID- 12524320
TI  - Subsecond proton-hole propagation in bacteriorhodopsin.
AB  - The dynamics of proton transfer between the surface of purple membrane and the
      aqueous bulk have recently been investigated by the Laser Induced Proton Pulse
      Method. Following a Delta-function release of protons to the bulk, the system was
      seen to regain its state of equilibrium within a few hundreds of microseconds.
      These measurements set the time frame for the relaxation of any state of acid
      base disequilibrium between the bacteriorhodopsin's surface and the bulk. It was
      also deduced that the released protons react with the various proton binding
      within less than 10 micro s. In the present study, we monitored the photocycle
      and the proton-cycle of photo-excited bacteriorhodopsin, in the absence of added
      buffer, and calculated the proton balance between the Schiff base and the bulk
      phase in a time-resolved mode. It was noticed that the late phase of the M decay
      (beyond 1 ms) is characterized by a slow (subsecond) relaxation of
      disequilibrium, where the Schiff base is already reprotonated but the pyranine
      still retains protons. Thus, it appears that the protonation of D96 is a slow
      rate-limiting process that generates a "proton hole" in the cytoplasmic section
      of the protein. The velocity of the hole propagation is modulated by the ionic
      strength of the solution and by selective replacements of charged residues on the
      interhelical loops of the protein, at domains that seems to be remote from the
      intraprotein proton conduction trajectory.

PMID- 12524321
TI  - The control of seizure-like activity in the rat hippocampal slice.
AB  - The sudden and transient hypersynchrony of neuronal firing that characterizes
      epileptic seizures can be considered as the transitory stabilization of
      metastable states present within the dynamical repertoire of a neuronal network.
      Using an in vitro model of recurrent spontaneous seizures in the rat horizontal
      hippocampal slice preparation, we present an approach to characterize the
      dynamics of the transition to seizure, and to use this information to control the
      activity and avoid the occurrence of seizure-like events. The transition from the
      interictal activity (between seizures) to the seizure-like event is aborted by
      brief (20-50 s) low-frequency (0.5 Hz) periodic forcing perturbations, applied
      via an extracellular stimulating electrode to the mossy fibers, the axons of the
      dentate neurons that synapse onto the CA3 pyramidal cells. This perturbation
      results in the stabilization of an interictal-like low-frequency firing pattern
      in the hippocampal slice. The results derived from this work shed light on the
      dynamics of the transition to seizure and will further the development of
      algorithms that can be used in automated devices to stop seizure occurrence.

PMID- 12524322
TI  - Ca2+ entry-dependent inactivation of L-type Ca current: a novel formulation for
      cardiac action potential models.
AB  - Cardiac L-type Ca current (I(Ca,L)) is controlled not only by voltage but also by
      Ca(2+)-dependent mechanisms. Precise implementation of I(Ca,L) in cardiac action
      potential models therefore requires thorough understanding of intracellular
      Ca(2+) dynamics, which is not yet available. Here, we present a novel formulation
      of I(Ca,L) for action potential models that does not explicitly require the
      knowledge of local intracellular Ca(2+) concentration ([Ca(2+)](i)). In this
      model, whereas I(Ca,L) is obtained as the product of voltage-dependent gating
      parameters (d and f), Ca(2+)-dependent inactivation parameters (f(Ca): f(Ca
      entry) and f(Ca-SR)), and Goldman-Hodgkin-Katz current equation as in previous
      studies, f(Ca) is not a instantaneous function of [Ca(2+)](i) but is determined
      by two terms: onset of inactivation proportional to the influx of Ca(2+) and time
      dependent recovery (dissociation). We evaluated the new I(Ca,L) subsystem in the
      framework of the standard cardiac action potential model. The new formulation
      produced a similar temporal profile of I(Ca,L) as the standard, but with
      different gating mechanisms. Ca(2+)-dependent inactivation gradually proceeded
      throughout the plateau phase, replacing the voltage-dependent inactivation
      parameter in the LRd model. In typical computations, f declined to approximately
      0.7 and f(Ca-entry) to approximately 0.1, whereas deactivation caused fading of
      I(Ca,L) during final repolarization. These results support experimental findings
      that Ca(2+) entering through I(Ca,L) is essential for inactivation. After
      responses to standard voltage-clamp protocols were examined, the new model was
      applied to analyze the behavior of I(Ca,L) when action potential was prolonged by
      several maneuvers. Our study provides a basis for theoretical analysis of I(Ca,L)
      during action potentials, including the cases encountered in long QT syndromes.

PMID- 12524323
TI  - Slow deactivation and U-shaped inactivation properties in cloned Cav1.2b channels
      in Chinese hamster ovary cells.
AB  - Whole-cell patch-clamp techniques were applied to Chinese hamster ovary cells
      stably expressing cloned smooth muscle Ca(2+) channel alpha(1)-subunits. In the
      presence of Ba(2+) as a charge carrier, U-shaped inactivation was observed in the
      presence and absence of Ca(2+) agonists. Also, tail currents deactivated slowly
      when conditioning steps of positive potential were applied. The deactivation time
      constant was decreased by hyperpolarizing the repolarization step. Application of
      ATP-gamma-S or H-7 had little effect on the conditions necessary to induce slow
      tail, suggesting involvement of physical processes in the channel protein. In the
      presence of Bay K 8644, additional application of nifedipine decreased the
      amplitudes of the test and tail currents induced by a test step preceded by a
      conditioning step to +80 mV, but did not affect the decay time constant of the
      tail current. From these results and assumptions we have drawn up a kinetic
      scheme with one closed state, two open states (O(1), O(2)) and two inactivated
      states linked to the closed state and open state O(1), respectively, i.e., open
      state O(2) protected from inactivation. Computer calculation reconstructed slow
      deactivation and U-shaped inactivation properties. A similar kinetic scheme with
      Ca(2+)-agonist-binding states accounted for the results in the presence of Ca(2+)
      agonists.

PMID- 12524324
TI  - A closer look at the canonical 'Raft Mixture' in model membrane studies.

PMID- 12524325
TI  - The binding of cofactors to photosystem I analyzed by spectroscopic and mutagenic
      methods.
AB  - This review focuses on cofactor-ligand and protein-protein interactions within
      the photosystem I reaction center. The topics include a description of the
      electron transfer cofactors, the mode of binding of the cofactors to protein
      bound ligands, and a description of intraprotein contacts that ultimately allow
      photosystem I to be assembled (in cyanobacteria) from 96 chlorophylls, 22
      carotenoids, 2 phylloquinones, 3 [4Fe-4S] clusters, and 12 polypeptides. During
      the 15 years that have elapsed from the first report of crystals to the atomic
      resolution X-ray crystal structure, cofactor-ligand interactions and protein
      protein interactions were systematically being explored by spectroscopic and
      genetic methods. This article charts the interplay between these disciplines and
      assesses how good the early insights were in light of the current structure of
      photosystem I.

PMID- 12524326
TI  - One lucky XX male: isolation of the first Caenorhabditis elegans sex
      determination mutants.

PMID- 12524327
TI  - The rate and character of spontaneous mutation in an RNA virus.
AB  - Estimates of spontaneous mutation rates for RNA viruses are few and uncertain,
      most notably due to their dependence on tiny mutation reporter sequences that may
      not well represent the whole genome. We report here an estimate of the
      spontaneous mutation rate of tobacco mosaic virus using an 804-base cognate
      mutational target, the viral MP gene that encodes the movement protein (MP).
      Selection against newly arising mutants was countered by providing MP function
      from a transgene. The estimated genomic mutation rate was on the lower side of
      the range previously estimated for lytic animal riboviruses. We also present the
      first unbiased riboviral mutational spectrum. The proportion of base
      substitutions is the same as that in a retrovirus but is lower than that in most
      DNA-based organisms. Although the MP mutant frequency was 0.02-0.05, 35% of the
      sequenced mutants contained two or more mutations. Therefore, the mutation
      process in populations of TMV and perhaps of riboviruses generally differs
      profoundly from that in populations of DNA-based microbes and may be strongly
      influenced by a subpopulation of mutator polymerases.

PMID- 12524328
TI  - Regulation of capsule synthesis and cell motility in Salmonella enterica by the
      essential gene igaA.
AB  - Mutants of Salmonella enterica carrying the igaA1 allele, selected as able to
      overgrow within fibroblast cells in culture, are mucoid and show reduced
      motility. Mucoidy is caused by derepression of wca genes (necessary for capsule
      synthesis); these genes are regulated by the RcsC/YojN/RcsB phosphorelay system
      and by the RcsA coregulator. The induction of wca expression in an igaA1 mutant
      is suppressed by mutations in rcsA and rcsC. Reduced motility is caused by
      lowered expression of the flagellar master operon, flhDC, and is suppressed by
      mutations in rcsB or rcsC, suggesting that mutations in the igaA gene reduce
      motility by activating the RcsB/C system. A null igaA allele can be maintained
      only in an igaA(+)/igaA merodiploid, indicating that igaA is an essential gene.
      Lethality is suppressed by mutations in rcsB, rcsC, and yojN, but not in rcsA,
      suggesting that the viability defect of an igaA null mutant is mediated by the
      RcsB/RcsC system, independently of RcsA (and therefore of the wca genes). Because
      all the defects associated with igaA mutations are suppressed by mutations that
      block the RcsB/RcsC system, we propose a functional interaction between the igaA
      gene product and either the Rcs regulatory network or one of its regulated
      products.

PMID- 12524329
TI  - Plasmids spread very fast in heterogeneous bacterial communities.
AB  - Conjugative plasmids can mediate gene transfer between bacterial taxa in diverse
      environments. The ability to donate the F-type conjugative plasmid R1 greatly
      varies among enteric bacteria due to the interaction of the system that represses
      sex-pili formations (products of finOP) of plasmids already harbored by a
      bacterial strain with those of the R1 plasmid. The presence of efficient donors
      in heterogeneous bacterial populations can accelerate plasmid transfer and can
      spread by several orders of magnitude. Such donors allow millions of other
      bacteria to acquire the plasmid in a matter of days whereas, in the absence of
      such strains, plasmid dissemination would take years. This "amplification effect"
      could have an impact on the evolution of bacterial pathogens that exist in
      heterogeneous bacterial communities because conjugative plasmids can carry
      virulence or antibiotic-resistance genes.

PMID- 12524330
TI  - Genome-wide analysis of synonymous single nucleotide polymorphisms in
      Mycobacterium tuberculosis complex organisms: resolution of genetic relationships
      among closely related microbial strains.
AB  - Several human pathogens (e.g., Bacillus anthracis, Yersinia pestis, Bordetella
      pertussis, Plasmodium falciparum, and Mycobacterium tuberculosis) have very
      restricted unselected allelic variation in structural genes, which hinders study
      of the genetic relationships among strains and strain-trait correlations. To
      address this problem in a representative pathogen, 432 M. tuberculosis complex
      strains from global sources were genotyped on the basis of 230 synonymous
      (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four
      genome sequences. Eight major clusters of related genotypes were identified in M.
      tuberculosis sensu stricto, including a single cluster representing organisms
      responsible for several large outbreaks in the United States and Asia. All M.
      tuberculosis sensu stricto isolates of previously unknown phylogenetic position
      could be rapidly and unambiguously assigned to one of the eight major clusters,
      thus providing a facile strategy for identifying organisms that are clonally
      related by descent. Common clones of M. tuberculosis sensu stricto and M. bovis
      are distinct, deeply branching genotypic complexes whose extant members did not
      emerge directly from one another in the recent past. sSNP genotyping rapidly
      delineates relationships among closely related strains of pathogenic microbes and
      allows construction of genetic frameworks for examining the distribution of
      biomedically relevant traits such as virulence, transmissibility, and host range.

PMID- 12524331
TI  - A defect of Kap104 alleviates the requirement of mitotic exit network gene
      functions in Saccharomyces cerevisiae.
AB  - A subgroup of the karyopherin beta (also called importin beta) protein that
      includes budding yeast Kap104 and human transportin/karyopherin beta2 is reported
      to function as a receptor for the transport of mRNA-binding proteins into the
      nucleus. We identified KAP104 as a responsible gene for a suppressor mutation of
      cdc15-2. We found that the kap104-E604K mutation suppressed the temperature
      sensitive growth of cdc15-2 cells by promoting the exit from mitosis and
      suppressed the temperature sensitivity of various mitotic-exit mutations. The
      cytokinesis defect of these mitotic-exit mutants was not suppressed by kap104
      E604K. Furthermore, the kap104-E604K mutation delays entry into DNA synthesis
      even at a permissive temperature. In cdc15-2 kap104-E604K cells, SWI5 and SIC1,
      but not CDH1, became essential at a high temperature, suggesting that the kap104
      E604K mutation promotes mitotic exit via the Swi5-Sic1 pathway. Interestingly,
      SPO12, which is involved in the release of Cdc14 from the nucleolus during early
      anaphase, also became essential in cdc15-2 kap104-E604K cells at a high
      temperature. The kap104-E604K mutation caused a partial delocalization of Cdc14
      from the nucleolus during interphase. This delocalization of Cdc14 was suppressed
      by the deletion of SPO12. These results suggest that a mutation in Kap104
      stimulates exit from mitosis through the activation of Cdc14 and implies a novel
      role for Kap104 in cell-cycle progression in budding yeast.

PMID- 12524332
TI  - Defects in SPT16 or POB3 (yFACT) in Saccharomyces cerevisiae cause dependence on
      the Hir/Hpc pathway: polymerase passage may degrade chromatin structure.
AB  - Spt16/Cdc68, Pob3, and Nhp6 collaborate in vitro and in vivo as the yeast factor
      SPN, which is homologous to human FACT. SPN/FACT complexes mediate passage of
      polymerases through nucleosomes and are important for both transcription and
      replication. An spt16 mutation was found to be intolerable when combined with a
      mutation in any member of the set of functionally related genes HIR1, HIR2/SPT1,
      HIR3/HPC1, or HPC2. Mutations in POB3, but not in NHP6A/B, also display strong
      synthetic defects with hir/hpc mutations. A screen for other mutations that cause
      dependence on HIR/HPC genes revealed genes encoding members of the Paf1 complex,
      which also promotes transcriptional elongation. The Hir/Hpc proteins affect the
      expression of histone genes and also promote normal deposition of nucleosomes;
      either role could explain an interaction with elongation factors. We show that
      both spt16 and pob3 mutants respond to changes in histone gene numbers, but in
      opposite ways, suggesting that Spt16 and Pob3 each interact with histones but
      perhaps with different subsets of these proteins. Supporting this, spt16 and pob3
      mutants also display different sensitivities to mutations in the N-terminal tails
      of histones H3 and H4 and to mutations in enzymes that modulate acetylation of
      these tails. Our results support a model in which SPN/FACT has two functions: it
      disrupts nucleosomes to allow polymerases to access DNA, and it reassembles the
      nucleosomes afterward. Mutations that impair the reassembly activity cause
      chromatin to accumulate in an abnormally disrupted state, imposing a requirement
      for a nucleosome reassembly function that we propose is provided by Hir/Hpc
      proteins.

PMID- 12524333
TI  - Candida albicans Mds3p, a conserved regulator of pH responses and virulence
      identified through insertional mutagenesis.
AB  - Candida albicans is a commensal fungus that causes diverse infections after
      antibiotic use or immune debilitation. Gene discovery has been limited because
      the organism is an asexual diploid. We have developed a strategy that yields
      random homozygous insertion mutants. The strategy has permitted identification of
      several prospective essential genes. Many of these genes are homologous to
      nonessential Saccharomyces cerevisiae genes, and some have no S. cerevisiae
      homolog. These findings may expand the range of antifungal drug targets. We have
      also identified new genes required for pH-dependent filamentation, a trait
      previously associated with virulence. One newly identified gene, MDS3, is
      required for expression in alkaline media of two filamentation-associated genes,
      HWP1 and ECE1, but is not required for expression of other pH-response genes. In
      S. cerevisiae, the two MDS3 homologs are required for growth in alkaline media,
      thus arguing that Mds3p function in adaptation to external pH changes is
      conserved. Epistasis tests show that Mds3p contributes to virulence and alkaline
      pH responses independently of the well-characterized Rim101p pH-response pathway.

PMID- 12524334
TI  - Differential processing of leading- and lagging-strand ends at Saccharomyces
      cerevisiae telomeres revealed by the absence of Rad27p nuclease.
AB  - Saccharomyces cerevisiae strains lacking the Rad27p nuclease, a homolog of the
      mammalian FEN-1 protein, display an accumulation of extensive single-stranded G
      tails at telomeres. Furthermore, the lengths of telomeric repeats become very
      heterogeneous. These phenotypes could be the result of aberrant Okazaki fragment
      processing of the C-rich strand, elongation of the G-rich strand by telomerase,
      or an abnormally high activity of the nucleolytic activities required to process
      leading-strand ends. To distinguish among these possibilities, we analyzed
      strains carrying a deletion of the RAD27 gene and also lacking genes required for
      in vivo telomerase activity. The results show that double-mutant strains died
      more rapidly than strains lacking only telomerase components. Furthermore, in
      such strains there is a significant reduction in the signals for G-tails as
      compared to those detected in rad27delta cells. The results from studies of the
      replication intermediates of a linear plasmid in rad27delta cells are consistent
      with the idea that only one end of the plasmid acquires extensive G-tails,
      presumably the end made by lagging-strand synthesis. These data further support
      the notion that chromosome ends have differential requirements for end
      processing, depending on whether the ends were replicated by leading- or lagging
      strand synthesis.

PMID- 12524335
TI  - Genetic and biochemical basis for viability of yeast lacking mitochondrial
      genomes.
AB  - Yme1p, an ATP-dependent protease localized in the mitochondrial inner membrane,
      is required for the growth of yeast lacking an intact mitochondrial genome.
      Specific dominant mutations in the genes encoding the alpha- and gamma-subunits
      of the mitochondrial F(1)F(0)-ATPase suppress the slow-growth phenotype of yeast
      that simultaneously lack Yme1p and mitochondrial DNA. F(1)F(0)-ATPase activity is
      reduced in yeast lacking Yme1p and is restored in yme1 strains bearing
      suppressing mutations in F(1)-ATPase structural genes. Mitochondria isolated from
      yme1 yeast generated a membrane potential upon the addition of succinate, but
      unlike mitochondria isolated either from wild-type yeast or from yeast bearing
      yme1 and a suppressing mutation, were unable to generate a membrane potential
      upon the addition of ATP. Nuclear-encoded F(0) subunits accumulate in yme1 yeast
      lacking mitochondrial DNA; however, deletion of genes encoding those subunits did
      not suppress the requirement of yme1 yeast for intact mitochondrial DNA. In
      contrast, deletion of INH1, which encodes an inhibitor of the F(1)F(0)-ATPase,
      partially suppressed the growth defect of yme1 yeast lacking mitochondrial DNA.
      We conclude that Yme1p is in part responsible for assuring sufficient F(1)F(0)
      ATPase activity to generate a membrane potential in mitochondria lacking
      mitochondrial DNA and propose that Yme1p accomplishes this by catalyzing the
      turnover of protein inhibitors of the F(1)F(0)-ATPase.

PMID- 12524336
TI  - SPN1, a conserved gene identified by suppression of a postrecruitment-defective
      yeast TATA-binding protein mutant.
AB  - Little is known about TATA-binding protein (TBP) functions after recruitment to
      the TATA element, although several TBP mutants display postrecruitment defects.
      Here we describe a genetic screen for suppressors of a postrecruitment-defective
      TBP allele. Suppression was achieved by a single point mutation in a previously
      uncharacterized Saccharomyces cerevisiae gene, SPN1 (suppresses postrecruitment
      functions gene number 1). SPN1 is an essential yeast gene that is highly
      conserved throughout evolution. The suppressing mutation in SPN1 substitutes an
      asparagine for an invariant lysine at position 192 (spn1(K192N)). The spn1(K192N)
      strain is able to suppress additional alleles of TBP that possess postrecruitment
      defects, but not a TBP allele that is postrecruitment competent. In addition,
      Spn1p does not stably associate with TFIID in vivo. Cells containing the
      spn1(K192N) allele exhibit a temperature-sensitive phenotype and some defects in
      activated transcription, whereas constitutive transcription appears relatively
      robust in the mutant background. Consistent with an important role in
      postrecruitment functions, transcription from the CYC1 promoter, which has been
      shown to be regulated by postrecruitment mechanisms, is enhanced in spn1(K192N)
      cells. Moreover, we find that SPN1 is a member of the SPT gene family, further
      supporting a functional requirement for the SPN1 gene product in transcriptional
      processes.

PMID- 12524337
TI  - kangaroo, a mobile element from Volvox carteri, is a member of a newly recognized
      third class of retrotransposons.
AB  - Retrotransposons play an important role in the evolution of genomic structure and
      function. Here we report on the characterization of a novel retrotransposon
      called kangaroo from the multicellular green alga, Volvox carteri. kangaroo
      elements are highly mobile and their expression is developmentally regulated.
      They probably integrate via double-stranded, closed-circle DNA intermediates
      through the action of an encoded recombinase related to the lambda-site-specific
      integrase. Phylogenetic analysis indicates that kangaroo elements are closely
      related to other unorthodox retrotransposons including PAT (from a nematode),
      DIRS-1 (from Dictyostelium), and DrDIRS1 (from zebrafish). PAT and kangaroo both
      contain split direct repeat (SDR) termini, and here we show that DIRS-1 and
      DrDIRS1 elements contain terminal features structurally related to SDRs. Thus,
      these mobile elements appear to define a third class of retrotransposons (the
      DIRS1 group) that are unified by common structural features, genes, and
      integration mechanisms, all of which differ from those of LTR and conventional
      non-LTR retrotransposons.

PMID- 12524338
TI  - A cuticle collagen encoded by the lon-3 gene may be a target of TGF-beta
      signaling in determining Caenorhabditis elegans body shape.
AB  - The signaling pathway initiated by the TGF-beta family member DBL-1 in
      Caenorhabditis elegans controls body shape in a dose-dependent manner. Loss-of
      function (lf) mutations in the dbl-1 gene cause a short, small body (Sma
      phenotype), whereas overexpression of dbl-1 causes a long body (Lon phenotype).
      To understand the cellular mechanisms underlying these phenotypes, we have
      isolated suppressors of the Sma phenotype resulting from a dbl-1(lf) mutation.
      Two of these suppressors are mutations in the lon-3 gene, of which four
      additional alleles are known. We show that lon-3 encodes a collagen that is a
      component of the C. elegans cuticle. Genetic and reporter-gene expression
      analyses suggest that lon-3 is involved in determination of body shape and is
      post-transcriptionally regulated by the dbl-1 pathway. These results support the
      possibility that TGF-beta signaling controls C. elegans body shape by regulating
      cuticle composition.

PMID- 12524339
TI  - Telomeric P elements associated with cytotype regulation of the P transposon
      family in Drosophila melanogaster.
AB  - P elements inserted at the left end of the Drosophila X chromosome were isolated
      genetically from wild-type P strains. Stocks carrying these elements were tested
      for repression of P-strain-induced gonadal dysgenesis in females and for
      repression of transposase-catalyzed P-element excision in males and females. Both
      traits were repressed by stocks carrying either complete or incomplete P elements
      inserted near the telomere of the X chromosome in cytological region 1A, but not
      by stocks carrying only nontelomeric X-linked P elements. All three of the
      telomeric P elements that were analyzed at the molecular level were inserted in
      one of the 1.8-kb telomere-associated sequence (TAS) repeats near the end of the
      X chromosome. Stocks with these telomeric P elements strongly repressed P-element
      excision induced in the male germline by a P strain or by the transposase
      producing transgenes H(hsp/CP)2, H(hsp/CP)3, a combination of these two
      transgenes, and P(ry(+), delta2-3)99B. For H(hsp/CP)2 and P(ry(+), delta2-3)99B,
      the repression was also effective when the flies were subjected to heat-shock
      treatments. However, these stocks did not repress the somatic transposase
      activity of P(ry(+), delta2-3)99B. Repression of transposase activity in the
      germline required maternal transmission of the telomeric P elements themselves.
      Paternal transmission of these elements, or maternal transmission of the
      cytoplasm from carriers, both were insufficient to repress transposase activity.
      Collectively, these findings indicate that the regulatory abilities of telomeric
      P elements are similar to those of the P cytotype.

PMID- 12524340
TI  - The genetic architecture of Drosophila sensory bristle number.
AB  - We have mapped quantitative trait loci (QTL) for Drosophila mechanosensory
      bristle number in six recombinant isogenic line (RIL) mapping populations, each
      of which was derived from an isogenic chromosome extracted from a line selected
      for high or low, sternopleural or abdominal bristle number and an isogenic wild
      type chromosome. All RILs were evaluated as male and female F(1) progeny of
      crosses to both the selected and the wild-type parental chromosomes at three
      developmental temperatures (18 degrees, 25 degrees, and 28 degrees ). QTL for
      bristle number were mapped separately for each chromosome, trait, and environment
      by linkage to roo transposable element marker loci, using composite interval
      mapping. A total of 53 QTL were detected, of which 33 affected sternopleural
      bristle number, 31 affected abdominal bristle number, and 11 affected both
      traits. The effects of most QTL were conditional on sex (27%), temperature (14%),
      or both sex and temperature (30%). Epistatic interactions between QTL were also
      common. While many QTL mapped to the same location as candidate bristle
      development loci, several QTL regions did not encompass obvious candidate genes.
      These features are germane to evolutionary models for the maintenance of genetic
      variation for quantitative traits, but complicate efforts to understand the
      molecular genetic basis of variation for complex traits.

PMID- 12524341
TI  - A Drosophila homologue of Sir2 modifies position-effect variegation but does not
      affect life span.
AB  - Control of chromosome structure is important in the regulation of gene
      expression, recombination, DNA repair, and chromosome stability. In a two-hybrid
      screen for proteins that interact with the Drosophila CREB-binding protein
      (dCBP), a known histone acetyltransferase and transcriptional coactivator, we
      identified the Drosophila homolog of a yeast chromatin regulator, Sir2. In yeast,
      Sir2 silences genes via an intrinsic NAD(+)-dependent histone deacetylase
      activity. In addition, Sir2 promotes longevity in yeast and in Caenorhabditis
      elegans. In this report, we characterize the Drosophila Sir2 (dSir2) gene and its
      product and describe the generation of dSir2 amorphic alleles. We found that
      dSir2 expression is developmentally regulated and that dSir2 has an intrinsic
      NAD(+)-dependent histone deacetylase activity. The dSir2 mutants are viable,
      fertile, and recessive suppressors of position-effect variegation (PEV),
      indicating that, as in yeast, dSir2 is not an essential function for viability
      and is a regulator of heterochromatin formation and/or function. However,
      mutations in dSir2 do not shorten life span as predicted from studies in yeast
      and worms.

PMID- 12524342
TI  - A Drosophila homolog of the polyglutamine disease gene SCA2 is a dosage-sensitive
      regulator of actin filament formation.
AB  - Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by
      the expansion of a CAG repeat encoding a polyglutamine tract in ataxin-2, the
      SCA2 gene product. The normal cellular function of ataxin-2 and the mechanism by
      which polyglutamine expansion of ataxin-2 causes neurodegeneration remain
      unknown. In this study we have used genetic and molecular approaches to
      investigate the function of a Drosophila homolog of the SCA2 gene (Datx2). Like
      human ataxin-2, Datx2 is found throughout development in a variety of tissue
      types and localizes to the cytoplasm. Mutations that reduce Datx2 activity or
      transgenic overexpression of Datx2 result in female sterility, aberrant sensory
      bristle morphology, loss or degeneration of tissues, and lethality. These
      phenotypes appear to result from actin filament formation defects occurring
      downstream of actin synthesis. Further studies demonstrate that Datx2 does not
      assemble with actin filaments, suggesting that the role of Datx2 in actin
      filament formation is indirect. These results indicate that Datx2 is a dosage
      sensitive regulator of actin filament formation. Given that loss of cytoskeleton
      dependent dendritic structure defines an early event in SCA2 pathogenesis, our
      findings suggest the possibility that dysregulation of actin cytoskeletal
      structure resulting from altered ataxin-2 activity is responsible for
      neurodegeneration in SCA2.

PMID- 12524343
TI  - The fruitless gene is required for the proper formation of axonal tracts in the
      embryonic central nervous system of Drosophila.
AB  - The fruitless (fru) gene in Drosophila melanogaster is a multifunctional gene
      that has sex-specific functions in the regulation of male sexual behavior and sex
      nonspecific functions affecting adult viability and external morphology. While
      much attention has focused on fru's sex-specific roles, less is known about its
      sex-nonspecific functions. We have examined fru's sex-nonspecific role in
      embryonic neural development. fru transcripts from sex-nonspecific promoters are
      expressed beginning at the earliest stages of neurogenesis, and Fru proteins are
      present in both neurons and glia. In embryos that lack most or all fru function,
      FasII- and BP102-positive axons have defasciculation defects and grow along
      abnormal pathways in the CNS. These defects in axonal projections in fru mutants
      were rescued by the expression of specific UAS-fru transgenes under the control
      of a pan-neuronal scabrous-GAL4 driver. Our results suggest that one of fru's sex
      nonspecific roles is to regulate the pathfinding ability of axons in the
      embryonic CNS.

PMID- 12524344
TI  - Molecular population genetics of Xdh and the evolution of base composition in
      Drosophila.
AB  - Few loci have been measured for DNA polymorphism and divergence in several
      species. Here we report such data from the protein-coding region of xanthine
      dehydrogenase (Xdh) in 22 species of Drosophila. Many of our samples were from
      closely related species, allowing us to confidently assign substitutions to
      individual lineages. Surprisingly, Xdh appears to be fixing more A/T mutations
      than G/C mutations in most lineages, leading to evolution of higher A/T content
      in the recent past. We found no compelling evidence for selection on protein
      variation, though some aspects of the data support the notion that a significant
      fraction of amino acid polymorphisms are slightly deleterious. Finally, we found
      no convincing evidence that levels of silent heterozygosity are associated with
      rates of protein evolution.

PMID- 12524345
TI  - Evolution of the integral membrane desaturase gene family in moths and flies.
AB  - Lepidopteran insects use sex pheromones derived from fatty acids in their species
      specific mate recognition system. Desaturases play a particularly prominent role
      in the generation of structural diversity in lepidopteran pheromone biosynthesis
      as a result of the diverse enzymatic properties they have evolved. These enzymes
      are homologous to the integral membrane desaturases, which play a primary role in
      cold adaptation in eukaryotic cells. In this investigation, we screened for
      desaturase-encoding sequences in pheromone glands of adult females of eight
      lepidopteran species. We found, on average, six unique desaturase-encoding
      sequences in moth pheromone glands, the same number as is found in the genome
      database of the fly, Drosophila melanogaster, vs. only one to three in other
      characterized eukaryotic genomes. The latter observation suggests the expansion
      of this gene family in insects before the divergence of lepidopteran and dipteran
      lineages. We present the inferred homology relationships among these sequences,
      analyze nonsynonymous and synonymous substitution rates for evidence of positive
      selection, identify sequence and structural correlates of three lineages
      containing characterized enzymatically distinct desaturases, and discuss the
      evolution of this sequence family in insects.

PMID- 12524346
TI  - Genomic effects of nucleotide substitutions in Drosophila simulans.
AB  - Selective fixation of beneficial mutations reduces levels of linked, neutral
      variation. The magnitude of this "hitchhiking effect" is determined by the
      strength of selection and the recombination rate between selected and neutral
      sites. Thus, depending on the values of these parameters and the frequency with
      which directional selection occurs, the genomic scale over which directional
      selection reduces levels of linked variation may vary widely. Here we present a
      permutation-based analysis of nucleotide polymorphisms and fixations in
      Drosophila simulans. We show evidence of pervasive small-scale hitchhiking
      effects in this lineage. Furthermore, our results reveal that different types of
      fixations are associated with different levels of linked variation.

PMID- 12524347
TI  - A role for the Drosophila SU(VAR)3-9 protein in chromatin organization at the
      histone gene cluster and in suppression of position-effect variegation.
AB  - Mutations in the gene for Su(var)3-9 are dominant suppressors of position-effect
      variegation (PEV). We show that SU(VAR)3-9 is a chromatin-associated protein and
      identify the large multicopy histone gene cluster (HIS-C) as one of its target
      loci. The organization of nucleosomes over the entire HIS-C region is altered in
      Su(var)3-9 mutants and there is a concomitant increase in expression of the
      histone genes. SU(VAR)3-9 is a histone H3 methyltransferase and, using chromatin
      immunoprecipitation, we show that SU(VAR)3-9 is present at the HIS-C locus and
      that the histone H3 at the HIS-C locus is methylated. We propose that SU(VAR)3-9
      is involved in packaging HIS-C into a distinct chromatin domain that has some of
      the characteristics of beta-heterochromatin. We suggest that methylation of
      histone H3 is important for the chromatin structure at HIS-C. The chromosomal
      deficiency for the HIS-C is also a suppressor of PEV. In contrast to what might
      be expected, we show that hemizygosity for the HIS-C locus leads to a substantial
      increase in the histone transcripts.

PMID- 12524349
TI  - Persistence of Mhc heterozygosity in homozygous clonal killifish, Rivulus
      marmoratus: implications for the origin of hermaphroditism.
AB  - The mangrove killifish Rivulus marmoratus, a neotropical fish in the order
      Cyprinodontiformes, is the only known obligatorily selfing, synchronous
      hermaphroditic vertebrate. To shed light on its population structure and the
      origin of hermaphroditism, major histocompatibility complex (Mhc) class I genes
      of the killifish from seven different localities in Florida, Belize, and the
      Bahamas were cloned and sequenced. Thirteen loci and their alleles were
      identified and classified into eight groups. The loci apparently arose
      approximately 20 million years ago (MYA) by gene duplications from a single
      common progenitor in the ancestors of R. marmoratus and its closest relatives.
      Distinct loci were found to be restricted to different populations and different
      individuals in the same population. Up to 44% of the fish were heterozygotes at
      Mhc loci, as compared to near homozygosity at non-Mhc loci. Large genetic
      distances between some of the Mhc alleles revealed the presence of ancestral
      allelic lineages. Computer simulation designed to explain these findings
      indicated that selfing is incomplete in R. marmoratus populations, that Mhc
      allelic lineages must have diverged before the onset of selfing, and that the
      hermaphroditism arose in a population containing multiple ancestral Mhc lineages.
      A model is proposed in which hermaphroditism arose stage-wise by mutations, each
      of which spread through the entire population and was fixed independently in the
      emerging clones.

PMID- 12524348
TI  - lingerer, a Drosophila gene involved in initiation and termination of copulation,
      encodes a set of novel cytoplasmic proteins.
AB  - In an effort to uncover genetic components underlying the courtship behavior of
      Drosophila melanogaster, we have characterized a novel gene, lingerer (lig),
      mutations of which result in abnormal copulation. Males carrying a hypomorphic
      mutation in lig fail to withdraw their genitalia upon termination of copulation,
      but display no overt abnormalities in their genitalia. A severe reduction in the
      dosage of the lig gene causes repeated attempted copulations but no successful
      copulations. Complete loss of lig function results in lethality during early
      pupal stages. lig is localized to polytene segment 44A on the second chromosome
      and encodes three alternatively spliced transcripts that generate two types of
      150-kD proteins, Lig-A and Lig-B, differing only at the C terminus. Lig proteins
      show no similarity to known proteins. However, a set of homologous proteins in
      mammals suggest that Drosophila Lig belongs to a family of proteins that share
      five highly conserved domains. Lig is a cytoplasmic protein expressed in the
      central nervous system (CNS), imaginal discs, and gonads. Lig-A expression is
      selectively reduced in lig mutants and the ubiquitous supply of this protein at
      the beginning of metamorphosis restores the copulatory defects of the lig mutant.
      We propose that lig may act in the nervous system to mediate the control of
      copulatory organs during courtship.

PMID- 12524350
TI  - The evolution of isochores: evidence from SNP frequency distributions.
AB  - The large-scale systematic variation in nucleotide composition along mammalian
      and avian genomes has been a focus of the debate between neutralist and
      selectionist views of molecular evolution. Here we test whether the compositional
      variation is due to mutation bias using two new tests, which do not assume
      compositional equilibrium. In the first test we assume a standard population
      genetics model, but in the second we make no assumptions about the underlying
      population genetics. We apply the tests to single-nucleotide polymorphism data
      from noncoding regions of the human genome. Both models of neutral mutation bias
      fit the frequency distributions of SNPs segregating in low- and medium-GC-content
      regions of the genome adequately, although both suggest compositional
      nonequilibrium. However, neither model fits the frequency distribution of SNPs
      from the high-GC-content regions. In contrast, a simple population genetics model
      that incorporates selection or biased gene conversion cannot be rejected. The
      results suggest that mutation biases are not solely responsible for the
      compositional biases found in noncoding regions.

PMID- 12524351
TI  - Likelihood and Bayes estimation of ancestral population sizes in hominoids using
      data from multiple loci.
AB  - Polymorphisms in an ancestral population can cause conflicts between gene trees
      and the species tree. Such conflicts can be used to estimate ancestral population
      sizes when data from multiple loci are available. In this article I extend
      previous work for estimating ancestral population sizes to analyze sequence data
      from three species under a finite-site nucleotide substitution model. Both
      maximum-likelihood (ML) and Bayes methods are implemented for joint estimation of
      the two speciation dates and the two population size parameters. Both methods
      account for uncertainties in the gene tree due to few informative sites at each
      locus and make an efficient use of information in the data. The Bayes algorithm
      using Markov chain Monte Carlo (MCMC) enjoys a computational advantage over ML
      and also provides a framework for incorporating prior information about the
      parameters. The methods are applied to a data set of 53 nuclear noncoding contigs
      from human, chimpanzee, and gorilla published by Chen and Li. Estimates of the
      effective population size for the common ancestor of humans and chimpanzees by
      both ML and Bayes methods are approximately 12,000-21,000, comparable to
      estimates for modern humans, and do not support the notion of a dramatic size
      reduction in early human populations. Estimates published previously from the
      same data are several times larger and appear to be biased due to methodological
      deficiency. The divergence between humans and chimpanzees is dated at
      approximately 5.2 million years ago and the gorilla divergence 1.1-1.7 million
      years earlier. The analysis suggests that typical data sets contain useful
      information about the ancestral population sizes and that it is advantageous to
      analyze data of several species simultaneously.

PMID- 12524352
TI  - Accelerated protein evolution and origins of human-specific features: Foxp2 as an
      example.
AB  - Genes responsible for human-specific phenotypes may have been under altered
      selective pressures in human evolution and thus exhibit changes in substitution
      rate and pattern at the protein sequence level. Using comparative analysis of
      human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and
      FOXP2) with significantly enhanced evolutionary rates in the hominid lineage.
      PRM2 is a histone-like protein essential to spermatogenesis and was previously
      reported to be a likely target of sexual selection in humans and chimpanzees.
      FOXP2 is a transcription factor involved in speech and language development.
      Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated
      two fixed amino acid changes in a broadly defined transcription suppression
      domain. A survey of a diverse group of placental mammals reveals the uniqueness
      of the human FOXP2 sequence and a population genetic analysis indicates possible
      adaptive selection behind the accelerated evolution. Taken together, our results
      suggest an important role that FOXP2 may have played in the origin of human
      speech and demonstrate a strategy for identifying candidate genes underlying the
      emergences of human-specific features.

PMID- 12524353
TI  - Vanishing GC-rich isochores in mammalian genomes.
AB  - To understand the origin and evolution of isochores-the peculiar spatial
      distribution of GC content within mammalian genomes-we analyzed the synonymous
      substitution pattern in coding sequences from closely related species in
      different mammalian orders. In primate and cetartiodactyls, GC-rich genes are
      undergoing a large excess of GC --> AT substitutions over AT --> GC
      substitutions: GC-rich isochores are slowly disappearing from the genome of these
      two mammalian orders. In rodents, our analyses suggest both a decrease in GC
      content of GC-rich isochores and an increase in GC-poor isochores, but more data
      will be necessary to assess the significance of this pattern. These observations
      question the conclusions of previous works that assumed that base composition was
      at equilibrium. Analysis of allele frequency in human polymorphism data, however,
      confirmed that in the GC-rich parts of the genome, GC alleles have a higher
      probability of fixation than AT alleles. This fixation bias appears not strong
      enough to overcome the large excess of GC --> AT mutations. Thus, whatever the
      evolutionary force (neutral or selective) at the origin of GC-rich isochores,
      this force is no longer effective in mammals. We propose a model based on the
      biased gene conversion hypothesis that accounts for the origin of GC-rich
      isochores in the ancestral amniote genome and for their decline in present-day
      mammals.

PMID- 12524354
TI  - Nucleotide variability at G6pd and the signature of malarial selection in humans.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common
      enzymopathy in humans. Deficiency alleles for this X-linked disorder are
      geographically correlated with historical patterns of malaria, and the most
      common deficiency allele in Africa (G6PD A-) has been shown to confer some
      resistance to malaria in both hemizygous males and heterozygous females. We
      studied DNA sequence variation in 5.1 kb of G6pd from 47 individuals representing
      a worldwide sample to examine the impact of selection on patterns of human
      nucleotide diversity and to infer the evolutionary history of the G6PD A- allele.
      We also sequenced 3.7 kb of a neighboring locus, L1cam, from the same set of
      individuals to study the effect of selection on patterns of linkage
      disequilibrium. Despite strong clinical evidence for malarial selection
      maintaining G6PD deficiency alleles in human populations, the overall level of
      nucleotide heterozygosity at G6pd is typical of other genes on the X chromosome.
      However, the signature of selection is evident in the absence of genetic
      variation among A- alleles from different parts of Africa and in the unusually
      high levels of linkage disequilibrium over a considerable distance of the X
      chromosome. In spite of a long-term association between Plasmodium falciparum and
      the ancestors of modern humans, patterns of nucleotide variability and linkage
      disequilibrium suggest that the A- allele arose in Africa only within the last
      10,000 years and spread due to selection.

PMID- 12524355
TI  - A genome scan for quantitative trait loci in a wild population of red deer
      (Cervus elaphus).
AB  - Recent empirical evidence indicates that although fitness and fitness components
      tend to have low heritability in natural populations, they may nonetheless have
      relatively large components of additive genetic variance. The molecular basis of
      additive genetic variation has been investigated in model organisms but never in
      the wild. In this article we describe an attempt to map quantitative trait loci
      (QTL) for birth weight (a trait positively associated with overall fitness) in an
      unmanipulated, wild population of red deer (Cervus elaphus). Two approaches were
      used: interval mapping by linear regression within half-sib families and a
      variance components analysis of a six-generation pedigree of >350 animals.
      Evidence for segregating QTL was found on three linkage groups, one of which was
      significant at the genome-wide suggestive linkage threshold. To our knowledge
      this is the first time that a QTL for any trait has been mapped in a wild mammal
      population. It is hoped that this study will stimulate further investigations of
      the genetic architecture of fitness traits in the wild.

PMID- 12524356
TI  - Novel loci control variation in reproductive timing in Arabidopsis thaliana in
      natural environments.
AB  - Molecular biologists are rapidly characterizing the genetic basis of flowering in
      model species such as Arabidopsis thaliana. However, it is not clear how the
      developmental pathways identified in controlled environments contribute to
      variation in reproductive timing in natural ecological settings. Here we report
      the first study of quantitative trait loci (QTL) for date of bolting (the
      transition from vegetative to reproductive growth) in A. thaliana in natural
      seasonal field environments and compare the results with those obtained under
      typical growth-chamber conditions. Two QTL specific to long days in the chamber
      were expressed only in spring-germinating cohorts in the field, and two loci
      specific to short days in the chamber were expressed only in fall-germinating
      cohorts, suggesting differential involvement of the photoperiod pathway in
      different seasonal environments. However, several other photoperiod-specific QTL
      with large effects in controlled conditions were undetectable in natural
      environments, indicating that expression of allelic variation at these loci was
      overridden by environmental factors specific to the field. Moreover, a
      substantial number of QTL with major effects on bolting date in one or more field
      environments were undetectable under controlled environment conditions. These
      novel loci suggest the involvement of additional genes in the transition to
      flowering under ecologically relevant conditions.

PMID- 12524357
TI  - Genetic dissection of an elite rice hybrid revealed that heterozygotes are not
      always advantageous for performance.
AB  - We introduced an experimental design that produced an "immortalized F(2)"
      population allowing for complete dissection of genetic components underlying
      quantitative traits. Data for yield and three component traits of the
      immortalized F(2) were collected from replicated field trials over 2 years. Using
      231 marker loci, we resolved the genetic effects into individual components and
      assessed relative performance of all the genotypes at both single- and two-locus
      levels. Single-locus analysis detected 40 QTL for the four traits. Dominance
      effects for about one-half of the QTL were negative, resulting in little "net"
      positive dominance effect. Correlation between genotype heterozygosity and trait
      performance was low. Large numbers of digenic interactions, including AA, AD, and
      DD, were detected for all the traits, with AA as the most prevalent interaction.
      Complementary two-locus homozygotes frequently performed the best among the nine
      genotypes of many two-locus combinations. While cumulative small advantages over
      two-locus combinations may partly explain the genetic basis of heterosis of the
      hybrid as double heterozygotes frequently demonstrated marginal advantages,
      double heterozygotes were never the best genotypes in any of the two-locus
      combinations. It was concluded that heterozygotes were not necessarily
      advantageous for trait performance even among genotypes derived from such a
      highly heterotic hybrid.

PMID- 12524358
TI  - Comparing relative rates of pollen and seed gene flow in the island model using
      nuclear and organelle measures of population structure.
AB  - We describe a method for comparing nuclear and organelle population
      differentiation (F(ST)) in seed plants to test the hypothesis that pollen and
      seed gene flow rates are equal. Wright's infinite island model is used, with
      arbitrary levels of self-fertilization and biparental organelle inheritance. The
      comparison can also be applied to gene flow in animals. Since effective
      population sizes are smaller for organelle genomes than for nuclear genomes and
      organelles are often uniparentally inherited, organelle F(ST) is expected to be
      higher at equilibrium than nuclear F(ST) even if pollen and seed gene flow rates
      are equal. To reject the null hypothesis of equal seed and pollen gene flow
      rates, nuclear and organelle F(ST)'s must differ significantly from their
      expected values under this hypothesis. Finite island model simulations indicate
      that infinite island model expectations are not greatly biased by finite numbers
      of populations (>/=100 subpopulations). The power to distinguish dissimilar rates
      of pollen and seed gene flow depends on confidence intervals for fixation index
      estimates, which shrink as more subpopulations and loci are sampled. Using data
      from the tropical tree Corythophora alta, we rejected the null hypothesis that
      seed and pollen gene flow rates are equal but cannot reject the alternative
      hypothesis that pollen gene flow is 200 times greater than seed gene flow.

PMID- 12524359
TI  - Embryo and endosperm development is disrupted in the female gametophytic capulet
      mutants of Arabidopsis.
AB  - The female gametophyte of higher plants gives rise, by double fertilization, to
      the diploid embryo and triploid endosperm, which develop in concert to produce
      the mature seed. What roles gametophytic maternal factors play in this process is
      not clear. The female-gametophytic effects on embryo and endosperm development in
      the Arabidopsis mea, fis, and fie mutants appear to be due to gametic imprinting
      that can be suppressed by METHYL TRANSFERASE1 antisense (MET1 a/s) transgene
      expression or by mutation of the DECREASE IN DNA METHYLATION1 (DDM1) gene. Here
      we describe two novel gametophytic maternal-effect mutants, capulet1 (cap1) and
      capulet2 (cap2). In the cap1 mutant, both embryo and endosperm development are
      arrested at early stages. In the cap2 mutant, endosperm development is blocked at
      very early stages, whereas embryos can develop to the early heart stage. The cap
      mutant phenotypes were not rescued by wild-type pollen nor by pollen from
      tetraploid plants. Furthermore, removal of silencing barriers from the paternal
      genome by MET1 a/s transgene expression or by the ddm1 mutation also failed to
      restore seed development in the cap mutants. Neither cap1 nor cap2 displayed
      autonomous seed development, in contrast to mea, fis, and fie mutants. In
      addition, cap2 was epistatic to fis1 in both autonomous endosperm and sexual
      development. Finally, both cap1 and cap2 mutant endosperms, like wild-type
      endosperms, expressed the paternally inactive endosperm-specific FIS2 promoter
      GUS fusion transgene only when the transgene was introduced via the embryo sac,
      indicating that imprinting was not affected. Our results suggest that the CAP
      genes represent novel maternal functions supplied by the female gametophyte that
      are required for embryo and endosperm development.

PMID- 12524360
TI  - Expression patterns and mutant phenotype of teosinte branched1 correlate with
      growth suppression in maize and teosinte.
AB  - The evolution of domesticated maize from its wild ancestor teosinte is a dramatic
      example of the effect of human selection on agricultural crops. Maize has one
      dominant axis of growth, whereas teosinte is highly branched. The axillary
      branches in maize are short and feminized whereas the axillary branches of
      teosinte are long and end in a male inflorescence under normal growth conditions.
      Previous QTL and molecular analysis suggested that the teosinte branched1 (tb1)
      gene of maize contributed to the architectural difference between maize and
      teosinte. tb1 mutants of maize resemble teosinte in their overall architecture.
      We analyzed the tb1 mutant phenotype in more detail and showed that the highly
      branched phenotype was due to the presence of secondary and tertiary axillary
      branching, as well as to an increase in the length of each node, rather than to
      an increase in the number of nodes. Double-mutant analysis with anther ear1 and
      tassel seed2 revealed that the sex of the axillary inflorescence was not
      correlated with its length. RNA in situ hybridization showed that tb1 was
      expressed in maize axillary meristems and in stamens of ear primordia, consistent
      with a function of suppressing growth of these tissues. Expression in teosinte
      inflorescence development suggests a role in pedicellate spikelet suppression.
      Our results provide support for a role for tb1 in growth suppression and reveal
      the specific tissues where suppression may occur.

PMID- 12524361
TI  - Genetic analysis, expression and molecular characterization of BoGSL-ELONG, a
      major gene involved in the aliphatic glucosinolate pathway of Brassica species.
AB  - We cloned a major aliphatic glucosinolate (GSL) gene, BoGSL-ELONG in Brassica
      oleracea, using the Arabidopsis sequence database. We based our work on an
      Arabidopsis candidate gene forming part of a gene family coding for isopropyl
      malate synthetase-like enzymes (IPMS). This gene is presumably responsible for
      synthesis of GSL possessing side chains consisting of four carbons (4C). The
      similarity of the Brassica homolog IPMS-Bo from broccoli to its Arabidopsis
      counterpart IPMS-At was on the order of 78%, both sharing the same number of
      exons. A nonfunctional allele of the BoGSL-ELONG gene from white cauliflower,
      based on the absence of 4C GSL in this crop, displayed a 30-bp deletion, which
      allowed us to develop a codominant marker for 4C-GSL. Gene expression analysis
      based on RT-PCR revealed a splicing site mutation in the white cauliflower
      allele. This resulted in a longer transcript containing intron 3, which failed to
      excise. Perfect cosegregation was observed for broccoli and cauliflower alleles
      at the IPMS-Bo gene and 4C-GSL content, strongly indicating that this gene indeed
      corresponds to BoGSL-ELONG. Cloning of two other major genes, BoGSL-ALK and BoGSL
      PRO, is underway. The availability of these genes and BoGSL-ELONG is essential
      for the manipulation of the aliphatic GSL profile of B. oleracea.

PMID- 12524362
TI  - Marker-assisted introgression of favorable alleles at quantitative trait loci
      between maize elite lines.
AB  - This article reports the marker-assisted introgression of favorable alleles at
      three quantitative trait loci (QTL) for earliness and grain yield among maize
      elite lines. The QTL were originally detected in 1992 by means of ANOVA in a
      population of 96 recombinant inbred lines (RILs). Introgression started from a
      selected RIL, which was crossed three times to one of the original parents and
      then self-fertilized, leading to BC(3)S(1) progenies. Markers were used to assist
      both foreground and background selection at each generation. At the end of the
      program, the effect of introgression was assessed phenotypically in agronomic
      trials, and QTL detection was performed by composite interval mapping among
      BC(3)S(1) progenies. The marker-assisted introgression proved successful at the
      genotypic level, as analyzed by precision graphical genotypes, although no
      emphasis was put on the reduction of linkage drag around QTL. Also, QTL positions
      were generally sustained in the introgression background. For earliness, the
      magnitude and sign of the QTL effects were in good agreement with those expected
      from initial RIL analyses. Conversely, for yield, important discrepancies were
      observed in the magnitude and sign of the QTL effects observed after
      introgression, when compared to those expected from initial RIL analyses. These
      discrepancies are probably due to important genotype-by-environment interactions.

PMID- 12524364
TI  - The pam1 gene is required for meiotic bouquet formation and efficient homologous
      synapsis in maize (Zea mays L.).
AB  - The clustering of telomeres on the nuclear envelope (NE) during meiotic prophase
      to form the bouquet arrangement of chromosomes may facilitate homologous
      chromosome synapsis. The pam1 (plural abnormalities of meiosis 1) gene is the
      first maize gene that appears to be required for telomere clustering, and
      homologous synapsis is impaired in pam1. Telomere clustering on the NE is
      arrested or delayed at an intermediate stage in pam1. Telomeres associate with
      the NE during the leptotene-zygotene transition but cluster slowly if at all as
      meiosis proceeds. Intermediate stages in telomere clustering including
      miniclusters are observed in pam1 but not in wild-type meiocytes. The tight
      bouquet normally seen at zygotene is a rare event. In contrast, the polarization
      of centromeres vs. telomeres in the nucleus at the leptotene-zygotene transition
      is the same in mutant and wild-type cells. Defects in homologous chromosome
      synapsis include incomplete synapsis, nonhomologous synapsis, and unresolved
      interlocks. However, the number of RAD51 foci on chromosomes in pam1 is similar
      to that of wild type. We suggest that the defects in homologous synapsis and the
      retardation of prophase I arise from the irregularity of telomere clustering and
      propose that pam1 is involved in the control of bouquet formation and downstream
      meiotic prophase I events.

PMID- 12524363
TI  - Organization, expression and evolution of a disease resistance gene cluster in
      soybean.
AB  - PCR amplification was previously used to identify a cluster of resistance gene
      analogues (RGAs) on soybean linkage group J. Resistance to powdery mildew (Rmd
      c), Phytophthora stem and root rot (Rps2), and an ineffective nodulation gene
      (Rj2) map within this cluster. BAC fingerprinting and RGA-specific primers were
      used to develop a contig of BAC clones spanning this region in cultivar "Williams
      82" [rps2, Rmd (adult onset), rj2]. Two cDNAs with homology to the TIR/NBD/LRR
      family of R-genes have also been mapped to opposite ends of a BAC in the contig
      Gm_Isb001_091F11 (BAC 91F11). Sequence analyses of BAC 91F11 identified 16
      different resistance-like gene (RLG) sequences with homology to the TIR/NBD/LRR
      family of disease resistance genes. Four of these RLGs represent two potentially
      novel classes of disease resistance genes: TIR/NBD domains fused inframe to a
      putative defense-related protein (NtPRp27-like) and TIR domains fused inframe to
      soybean calmodulin Ca(2+)-binding domains. RT-PCR analyses using gene-specific
      primers allowed us to monitor the expression of individual genes in different
      tissues and developmental stages. Three genes appeared to be constitutively
      expressed, while three were differentially expressed. Analyses of the R-genes
      within this BAC suggest that R-gene evolution in soybean is a complex and dynamic
      process.

PMID- 12524365
TI  - A cluster of four receptor-like genes resides in the Vf locus that confers
      resistance to apple scab disease.
AB  - The Vf locus, derived from the crabapple species Malus floribunda 821, confers
      resistance to five races of the fungal pathogen Venturia inaequalis, the causal
      agent of apple scab disease. In our previous research, the Vf locus was
      restricted to a BAC contig of approximately 290 kb covered by five overlapping
      BAC clones. Here, we report on cloning of the resistance gene(s) present in the
      Vf BAC contig using a highly reliable and straightforward approach. This approach
      relies on hybridization of labeled cDNAs to amplified inserts of subclones
      derived from BAC inserts, followed by recovery of full-size transcripts by rapid
      amplification of cDNA ends (RACE). A cluster of four resistance paralogs (Vfa1,
      Vfa2, Vfa3, and Vfa4) was identified in the Vf locus. Vfa1, Vfa2 and Vfa4 had no
      introns and are predicted to encode proteins characterized with extracellular
      leucine-rich repeats (LRRs) and transmembrane (TM) domains. However, Vfa3
      contains an insertion of 780 bp at the end of the LRR motif, resulting in
      multiple truncated transcripts. Comparison of Vfa1, Vfa2, and Vfa4 paralogs
      revealed a high degree of overall homology in their deduced amino acid sequences,
      while divergences were mainly restricted within LRR domains, including variable
      LRR units, numerous amino acid substitutions, and several residue
      deletions/duplications. Differential expression profiles among the four paralogs
      were observed during leaf development. Vfa1, Vfa2, and Vfa3 were active in
      immature leaves, but slightly expressed in mature leaves, while Vfa4 was active
      in immature leaves and was highly expressed in mature leaves.

PMID- 12524366
TI  - The influence of linkage and inbreeding on patterns of nucleotide sequence
      diversity at duplicate alcohol dehydrogenase loci in wild barley (Hordeum vulgare
      ssp. spontaneum).
AB  - Patterns of nucleotide sequence diversity are analyzed for three duplicate
      alcohol dehydrogenase loci (adh1-adh3) within a species-wide sample of 25
      accessions of wild barley (Hordeum vulgare ssp. spontaneum). The adh1 and adh2
      loci are tightly linked (recombination fraction <0.01) while the adh3 locus is
      inherited independently. Wild barley is predominantly self-fertilizing
      (approximately 98%), and as a consequence, effective recombination is restricted
      by the extreme reduction in heterozygosity. Large reductions in effective
      recombination, in turn, widen the conditions for linkage to influence nucleotide
      sequence diversity through the action of selective sweeps or background
      selection. These considerations would appear to predict (1) homogeneity in
      patterns of nucleotide sequence diversity, especially between closely linked
      loci, and (2) extensive linkage disequilibrium relative to random-mating species.
      In contrast to these expectations, the wild barley data reveal heterogeneity in
      patterns of nucleotide sequence diversity and levels of linkage disequilibrium
      that are indistinguishable from those observed at adh1 in maize, an outbreeding
      grass species.

PMID- 12524367
TI  - Changing effective population size and the McDonald-Kreitman test.
AB  - Artifactual evidence of adaptive amino acid substitution can be generated within
      a McDonald-Kreitman test if some amino acid mutations are slightly deleterious
      and there has been an increase in effective population size. Here I investigate
      the conditions under which this occurs. I show that fairly small increases in
      effective population size can generate artifactual evidence of positive selection
      if there is no selection upon synonymous codon use. This problem is exacerbated
      by the removal of low-frequency polymorphisms. However, selection on synonymous
      codon use restricts the conditions under which artifactual evidence of adaptive
      evolution is produced.

PMID- 12524368
TI  - Approximate Bayesian computation in population genetics.
AB  - We propose a new method for approximate Bayesian statistical inference on the
      basis of summary statistics. The method is suited to complex problems that arise
      in population genetics, extending ideas developed in this setting by earlier
      authors. Properties of the posterior distribution of a parameter, such as its
      mean or density curve, are approximated without explicit likelihood calculations.
      This is achieved by fitting a local-linear regression of simulated parameter
      values on simulated summary statistics, and then substituting the observed
      summary statistics into the regression equation. The method combines many of the
      advantages of Bayesian statistical inference with the computational efficiency of
      methods based on summary statistics. A key advantage of the method is that the
      nuisance parameters are automatically integrated out in the simulation step, so
      that the large numbers of nuisance parameters that arise in population genetics
      problems can be handled without difficulty. Simulation results indicate
      computational and statistical efficiency that compares favorably with those of
      alternative methods previously proposed in the literature. We also compare the
      relative efficiency of inferences obtained using methods based on summary
      statistics with those obtained directly from the data using MCMC.

PMID- 12524370
TI  - Context dependence of meiotic recombination hotspots in yeast: the relationship
      between recombination activity of a reporter construct and base composition.
AB  - Borde and colleagues reported that a reporter plasmid inserted at different
      genomic locations in Saccharomyces cerevisiae had different levels of meiotic
      recombination activity. We show that the level of recombination activity is very
      significantly correlated with the GC content of DNA sequences flanking the
      insertion.

PMID- 12524369
TI  - BEST: a novel computational approach for comparing gene expression patterns from
      early stages of Drosophila melanogaster development.
AB  - Embryonic gene expression patterns are an indispensable part of modern
      developmental biology. Currently, investigators must visually inspect numerous
      images containing embryonic expression patterns to identify spatially similar
      patterns for inferring potential genetic interactions. The lack of a
      computational approach to identify pattern similarities is an impediment to
      advancement in developmental biology research because of the rapidly increasing
      amount of available embryonic gene expression data. Therefore, we have developed
      computational approaches to automate the comparison of gene expression patterns
      contained in images of early stage Drosophila melanogaster embryos (prior to the
      beginning of germ-band elongation); similarities and differences in gene
      expression patterns in these early stages have extensive developmental effects.
      Here we describe a basic expression search tool (BEST) to retrieve best matching
      expression patterns for a given query expression pattern and a computational
      device for gene interaction inference using gene expression pattern images and
      information on the associated genotypes and probes. Analysis of a prototype
      collection of Drosophila gene expression pattern images is presented to
      demonstrate the utility of these methods in identifying biologically meaningful
      matches and inferring gene interactions by direct image content analysis. In
      particular, the use of BEST searches for gene expression patterns is akin to that
      of BLAST searches for finding similar sequences. These computational
      developmental biology methodologies are likely to make the great wealth of
      embryonic gene expression pattern data easily accessible and to accelerate the
      discovery of developmental networks.

PMID- 12524372
TI  - Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor
      responses in humans.
AB  - This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces
      adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness.
      Additionally, an exercise countermeasure group was included to identify whether
      exercise during bed rest might counteract any vasoconstrictor deficits that arose
      during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR.
      Eight of these 22 subjects did not exercise during HDBR, while 14 of these
      subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed
      rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor
      responsiveness, intradermal microdialysis was used to locally administer
      norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler
      flowmetry) was monitored over microdialysis membranes. Nonlinear regression
      modeling was used to identify the effective drug concentration that caused 50% of
      the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF
      NE dose-response curves. In addition, the effects of HDBR on nonadrenergic
      cutaneous vasoconstriction were assessed via the venoarteriolar response of the
      forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous
      vasoconstriction to exogenous NE administration regardless of whether the
      subjects exercised during HDBR. Moreover, HDBR did not alter the forearm
      venoarteriolar response in either the control or exercise groups during HDBR.
      However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction
      due to the venoarteriolar response in the leg, and this response was similarly
      reduced in the exercise group. These data suggest that HDBR does not alter
      cutaneous vasoconstrictor responses to exogenous NE administration, whereas
      cutaneous vasoconstriction of the leg due to the venoarteriolar response is
      reduced after HDBR. It remains unclear whether attenuated venoarteriolar
      responses in the lower limbs contribute to reduced orthostatic tolerance after
      bed rest and spaceflight.

PMID- 12524373
TI  - Vascular endothelial growth factor in patients with high-altitude pulmonary
      edema.
AB  - To examine the role of VEGF in the pathogenesis of high-altitude pulmonary edema
      (HAPE), we measured the concentrations of VEGF in venous serum and
      bronchoalveolar lavage fluid in patients with HAPE and in healthy volunteers. The
      VEGF in venous serum of the patients was normal at admission and significantly
      increased at recovery. Similarly, the VEGF in bronchoalveolar lavage fluid of the
      patients was increased at recovery compared with admission, but values at both
      admission and recovery were significantly lower than those of the controls. The
      present finding suggests that VEGF probably is destroyed in the lung of HAPE, and
      it appears less likely to have a critical part in the pathogenesis of HAPE but
      has rather an important role in the repair process for the impaired cell layer.

PMID- 12524374
TI  - Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset
      of exercise.
AB  - The purpose of this study was to test the hypothesis that sympathetic
      vasoconstriction is rapidly blunted at the onset of forearm exercise. Nine
      healthy subjects performed 5 min of moderate dynamic forearm handgrip exercise
      during -60 mmHg lower body negative pressure (LBNP) vs. without (control). Beat
      by-beat forearm blood flow (Doppler ultrasound), arterial blood pressure (finger
      photoplethysmograph), and heart rate were collected. LBNP elevated resting heart
      rate by approximately 45%. Mean arterial blood pressure was not significantly
      changed (P = 0.196), but diastolic blood pressure was elevated by approximately
      10% and pulse pressure was reduced by approximately 20%. At rest, there was a 30%
      reduction in forearm vascular conductance (FVC) during LBNP (P = 0.004). The
      initial rapid increase in FVC with exercise onset reached a plateau between 10
      and 20 s of 126.6 +/- 4.1 ml. min(-1). 100 mmHg(-1) in control vs. only 101.6 +/-
      4.1 ml. min(-1). 100 mmHg(-1) in LBNP (main effect of condition, P = 0.003). This
      difference was quickly abolished during the second, slower phase of adaptation in
      forearm vascular tone to steady state. These data are consistent with a rapid
      onset of functional sympatholysis, in which local substances released with the
      onset of muscle contractions impair sympathetic neural vasoconstrictor
      effectiveness.

PMID- 12524375
TI  - Nonlinear summation of force in cat tibialis anterior: a muscle with
      intrafascicularly terminating fibers.
AB  - The complex connective tissue structure of muscle and tendon suggests that forces
      from two parts of a muscle may not summate linearly, particularly in muscles with
      intrafasciculary terminating fibers, such as cat tibialis anterior (TA). In four
      anesthetized cats, the TA was attached to a servomechanism to control muscle
      length and record force. The ventral roots were divided into two bundles, each
      innervating about half the TA, so the two parts could be stimulated alone or
      together. Nonlinear summation of force (F(nl)) was measured during isometric
      contractions. F(nl) was small and negative, indicating less than linear summation
      of the parts, which is consistent with the predicted F(nl) of muscle fibers
      connected in series. F(nl) was more significant when smaller parts of the muscle
      were tested (21.8 vs. 8% for whole muscle). These data were fit to a model where
      both parts of the muscle were assumed to stretch a common elasticity.
      Compensatory movements of the servomechanism showed the common elasticity is very
      stiff, and the model cannot account for F(nl) in cat TA.

PMID- 12524376
TI  - Extrajugular pathways of human cerebral venous blood drainage assessed by duplex
      ultrasound.
AB  - Cerebral venous drainage in humans is thought to be ensured mainly via the
      internal jugular veins (IJVs). However, anatomic, angiographic, and ultrasound
      studies suggest that the vertebral venous system serves as an important
      alternative drainage route. We assessed venous blood volume flow in vertebral
      veins (VVs) and IJVs of 12 healthy volunteers using duplex ultrasound.
      Measurements were performed at rest and during a transient bilateral IJV and a
      circular neck compression. Total venous blood volume flow at rest was 766 +/- 226
      ml/min (IJVs: 720 +/- 232, VVs: 47 +/- 33 ml/min). During bilateral IJV
      compression, VV flow increased to 128 +/- 64 ml/min. Circular neck compression,
      causing an additional deep cervical vein obstruction, led to a further rise in VV
      volume flow (186 +/- 70 ml/min). As the observed flow increase did not compensate
      for IJV flow cessation, other parts of the vertebral venous system, like the
      intraspinal epidural veins and the deep cervical veins, have to be considered as
      additional alternative drainage pathways.

PMID- 12524377
TI  - Active glottal closure during central apneas limits oxygen desaturation in
      premature lambs.
AB  - Our laboratory previously reported that active glottal closure was present in 90%
      of spontaneous central apneas in premature lambs while maintaining a high-apneic
      lung volume (Renolleau S, Letourneau P, Niyonsenga T, and Praud JP. Am J Respir
      Crit Care Med 159: 1396-1404, 1999.) The present study aimed at testing whether
      this mechanism limits postapnea oxygen desaturation. Four premature lambs were
      instrumented for recording states of alertness, thyroarytenoid muscle and
      diaphragm electromyographic (EMG) activity, nasal airflow, lung volume changes,
      and pulse oximetry. One thousand four hundred fifty-two spontaneous central
      apneas (isolated or during periodic breathing) were analyzed in nonsedated lambs.
      Apneas, with high lung volume maintained by active glottal closure, were compared
      with apneas, with a tracheostomy opened at apnea onset. Oxygen desaturation
      slopes were lower when high-apneic lung volume was actively maintained during
      both wakefulness and quiet sleep. Furthermore, oxygen desaturation slopes were
      lower after isolated apneas with continuous thyroarytenoid EMG during
      wakefulness, compared with apneas with noncontinuous thyroarytenoid EMG (=
      glottis opened shortly after apnea onset). These results highlight the importance
      of maintaining high-alveolar oxygen stores during central apneas by active
      glottal closure to limit desaturation in newborns.

PMID- 12524378
TI  - Granulocyte colony-stimulating factor enhances alpha-naphthylthiourea-induced
      pulmonary hypertension.
AB  - Physiopathological discrepancies exist between the most widely used models of
      pulmonary hypertension (PH), namely monocrotaline- and hypoxia-induced PH. The
      development of a new model could help in the understanding of underlying
      mechanisms. Repeated alpha-naphthylthiourea (ANTU) injections (5 mg/kg weekly, 3
      wk) induced pulmonary vascular remodeling, which was associated with development
      of PH and right ventricular hypertrophy. ANTU followed by granulocyte colony
      stimulating factor (G-CSF; 25 microgram. kg(-1). day(-1) subcutaneously, 3
      days/wk) induced higher pulmonary arterial pressures and right ventricular
      hypertrophy than ANTU alone. Lidocaine, which inhibits neutrophil functions,
      inhibited PH exacerbation by G-CSF. Endothelial nitric oxide synthase expression,
      measured to assess ANTU-related endothelial toxicity, decreased significantly in
      ANTU-treated rats and fell even more sharply when G-CSF was given. This occurred
      despite a significant increase in vascular endothelial cell growth factor
      expression in lung and right ventricle in rats given ANTU alone and even more in
      rats given ANTU plus G-CSF. Repeated ANTU administration induces PH with vascular
      remodeling that can be further aggravated by the neutrophil activator G-CSF.

PMID- 12524379
TI  - Altered single cell force-velocity and power properties in exercise-trained rat
      myocardium.
AB  - Myocardial function is enhanced by endurance exercise training, but the cellular
      mechanisms underlying this improved function remain unclear. The ability of the
      myocardium to perform external work is a critical aspect of ventricular function,
      but previous studies of myocardial adaptation to exercise training have been
      limited to measurements of isometric tension or unloaded shortening velocity,
      conditions in which work output is zero. We measured force-velocity properties in
      single permeabilized myocyte preparations to determine the effect of exercise
      training on loaded shortening and power output. Female Sprague-Dawley rats were
      divided into sedentary control (C) and exercise trained (T) groups. T rats
      underwent 11 wk of progressive treadmill exercise. Myocytes were isolated from T
      and C hearts, chemically skinned, and attached to a force transducer. Shortening
      velocity was determined during loaded contractions at 15 degrees C by using a
      force-clamp technique. Power output was calculated by multiplying force times
      velocity values. We found that unloaded shortening velocity was not significantly
      different in T vs. C myocytes (T = 1.43 muscle lengths/s, n = 46 myocytes; C =
      1.12 muscle lengths/s, n = 43 myocytes). Training increased the velocity of
      loaded shortening and increased peak power output (peak power = 0.16 P/P(o) x
      muscle length/s for T myocytes; peak power = 0.10 P/P(o) x muscle length/s for C
      myocytes, where P/P(o) is relative tension). We found no effect of training on
      myosin heavy chain isoform content. These results suggest that training alters
      power output properties of single cardiac myocytes and that this adaptation may
      improve the work capacity of the myocardium.

PMID- 12524380
TI  - Spectral characteristics of airway opening and chest wall tidal flows in
      spontaneously breathing preterm infants.
AB  - We compared the harmonic content of tidal flows measured simultaneously at the
      mouth and chest wall in spontaneously breathing very low birth weight infants (n
      = 16, 1,114 +/- 230 g, gestation age: 28 +/- 2 wk). Airway opening flows were
      measured via face mask-pneumotachograph (P-tach), whereas chest wall flows were
      derived from respiratory inductance plethysmography (RIP) excursions. Next, for
      each, we computed two spectral shape indexes: 1) harmonic distortion (k(d); k(d,P
      tach) and k(d,RIP), respectively) defines the extent to which flows deviated from
      a single sine wave, and 2) the exponent of the power law (s; s(P-tach) and
      s(RIP), respectively), describing the spectral energy vs. frequency. P-tach and
      RIP flow spectra exhibited similar power law functional forms consistently in all
      infants. Also, mouth [s(P-tach) = 3.73 +/- 0.23% (95% confidence interval), k(d,P
      tach) = 38.8 +/- 4.6%] and chest wall (s(RIP) = 3.51 +/- 0.30%, k(d,RIP) = 42.8
      +/- 4.8%) indexes were similar and highly correlated (s(RIP) = 1.17 x s(P-tach) +
      0.85; r(2) = 0.81; k(d,RIP) = 0.90 x k(d,P-tach) + 8.0; r(2) = 0.76). The
      corresponding time to peak tidal expiratory flow-to-expiratory time ratio (0.62
      +/- 0.08) was higher than reported in older infants. The obtained s and k(d)
      values are similar to those reported in older and/or larger chronic lung disease
      infants, yet appreciably lower than for 1-mo-old healthy infants of closer age
      and/or size; this indicated increased complexity of tidal flows in very low birth
      weight babies. Importantly, we found equivalent flow spectral data from mouth and
      chest wall tidal flows. The latter are desirable because they avoid face mask
      artificial effects, including leaks around it, they do not interfere with
      ventilatory support delivery, and they may facilitate longer measurements that
      are useful in control of breathing assessment.

PMID- 12524381
TI  - Combined creatine and protein supplementation in conjunction with resistance
      training promotes muscle GLUT-4 content and glucose tolerance in humans.
AB  - The present study was undertaken to explore the effects of creatine and creatine
      plus protein supplementation on GLUT-4 and glycogen content of human skeletal
      muscle. This was investigated in muscles undergoing a decrease (immobilization)
      and subsequent increase (resistance training) in activity level, compared with
      muscles with unaltered activity pattern. A double-blind, placebo-controlled trial
      was performed by 33 young healthy subjects. The subjects' right legs were
      immobilized with a cast for 2 wk, followed by a 6-wk resistance training program
      for the right knee extensor muscles. The participants were supplemented
      throughout the study with either placebo (Pl group) or creatine (Cr group) or
      with creatine during immobilization and creatine plus protein during retraining
      (Cr+P group). Needle biopsies were bilaterally taken from the vastus lateralis.
      GLUT-4 protein expression was reduced by the immobilization in all groups (P <
      0.05). During retraining, GLUT-4 content increased (P < 0.05) in both Cr (+24%)
      and Cr+P (+33%), which resulted in higher posttraining GLUT-4 expression compared
      with Pl (P < 0.05). Compared with Pl, muscle glycogen content was higher (P <
      0.05) in the trained leg in both Cr and Cr+P. Supplements had no effect on GLUT-4
      expression or glycogen content in contralateral control legs. Area under the
      glucose curve during the oral glucose tolerance test was decreased from 232 +/-
      23 mmol. l(-1). min(-1) at baseline to 170 +/- 23 mmol. l(-1). min(-1) at the end
      of the retraining period in Cr+P (P < 0.05), but it did not change in Cr or Pl.
      We conclude that creatine intake stimulates GLUT-4 and glycogen content in human
      muscle only when combined with changes in habitual activity level. Furthermore,
      combined protein and creatine supplementation improved oral glucose tolerance,
      which is supposedly unrelated to the changes in muscle GLUT-4 expression.

PMID- 12524382
TI  - Afferent vagal pathways mediating respiratory reflexes evoked by ROS in the lungs
      of anesthetized rats.
AB  - We investigated the afferent vagal pathways mediating respiratory reflexes evoked
      by reactive oxygen species (ROS) in the lungs of anesthetized rats. Spontaneous
      inhalation of 0.2% aerosolized H(2)O(2) acutely evoked initial bradypnea followed
      by delayed tachypnea, which was frequently mixed with delayed augmented
      inspiration. The initial response was abolished after perivagal capsaicin
      treatment (PCT), but was prolonged during vagal cooling (VC) to 7 degrees C; PCT
      and VC are known to differentially block the conduction of unmyelinated C and
      myelinated fibers, respectively. The delayed responses were eliminated during VC
      but emerged earlier after PCT. Vagotomy, catalase (an antioxidant for H(2)O(2)),
      dimethylthiourea (an antioxidant for. OH), or deferoxamine (an antioxidant for.
      OH) largely or totally suppressed these reflexive responses, whereas sham nerve
      treatment, heat-inactivated catalase, saline vehicle, or iron-saturated
      deferoxamine failed to do so. These results suggest that 1) the H(2)O(2)-evoked
      initial and delayed airway reflexes are antagonistic and may result from
      stimulation of lung C fibers and rapidly adapting receptors, respectively, and 2)
      the reflex effects of H(2)O(2) are, in part, due to the action of. OH on these
      afferents.

PMID- 12524383
TI  - Collections and ficolins: humoral lectins of the innate immune defense.
AB  - Collectins and ficolins, present in plasma and on mucosal surfaces, are humoral
      molecules of the innate immune systems, which recognize pathogen-associated
      molecular patterns. The human collectins, mannan-binding lectin (MBL) and
      surfactant protein A and D (SP-A and SP-D), are oligomeric proteins composed of
      carbohydrate-recognition domains (CRDs) attached to collagenous regions and are
      thus structurally similar to the ficolins, L-ficolin, M-ficolin, and H-ficolin.
      However, they make use of different CRD structures: C-type lectin domains for the
      collectins and fibrinogen-like domains for the ficolins. Upon recognition of the
      infectious agent, MBL and the ficolins initiate the lectin pathway of complement
      activation through attached serine proteases (MASPs), whereas SP-A and SP-D rely
      on other effector mechanisms: direct opsonization, neutralization, and
      agglutination. This limits the infection and concurrently orchestrates the
      subsequent adaptive immune response. Deficiencies of the proteins may predispose
      to infections or other complications, e.g., reperfusion injuries or autoimmune
      diseases. Structure, function, clinical implications, and phylogeny are reviewed.

PMID- 12524384
TI  - IgA Fc receptors.
AB  - The IgA receptor family comprises a number of surface receptors including the
      polymeric Ig receptor involved in epithelial transport of IgA/IgM, the myeloid
      specific IgA Fc receptor (FcalphaRI or CD89), the Fcalpha/muR, and at least two
      alternative IgA receptors. These are the asialoglycoprotein receptor and the
      transferrin receptor, which have been implicated in IgA catabolism, and tissue
      IgA deposition. In this review we focus on the biology of FcalphaRI (CD89).
      FcalphaRI is expressed on neutrophils, eosinophils, monocytes/macrophages,
      dendritic cells, and Kupffer cells. This receptor represents a heterogeneously
      glycosylated transmembrane protein that binds both IgA subclasses with low
      affinity. A single gene encoding FcalphaRI has been isolated, which is located
      within the leukocyte receptor cluster on chromosome 19. The FcalphaRI alpha chain
      lacks canonical signal transduction domains but can associate with the FcR gamma
      chain that bears an activation motif (ITAM) in the cytoplasmic domain, allowing
      activatory functions. FcalphaRI expressed alone mediates endocytosis and recyling
      of IgA. No FcalphaRI homologue has been defined in the mouse, and progress in
      defining the in vivo role of FcalphaRI has been made using human FcalphaRI
      transgenic (Tg) mice. FcalphaRI-Tg mice demonstrated FcalphaRI expression on
      Kupffer cells and so defined a key role for the receptor in mucosal defense. The
      receptor functions as a second line of antibacterial defense involving serum IgA
      rather than secretory IgA. Studies in FcalphaRI-Tg mice, furthermore, defined an
      essential role for soluble FcalphaRI in the development of IgA nephropathy by
      formation of circulating IgA-FcalphaRI complexes. Finally, recent work points out
      a role for human IgA in treatment of infectious and neoplastic diseases.

PMID- 12524385
TI  - T cell dynamics in HIV-1 infection.
AB  - In the absence of antiretroviral treatment, HIV-1 establishes a chronic,
      progressive infection of the human immune system that invariably, over the course
      of years, leads to its destruction and fatal immunodeficiency. Paradoxically,
      while viral replication is extensive throughout the course of infection,
      deterioration of conventional measures of immunity is slow, including the
      characteristic loss of CD4(+) T cells that is thought to play a key role in the
      development of immunodeficiency. This conundrum suggests that CD4(+) T cell
      directed viral cytopathicity alone cannot explain the course of disease. Indeed,
      recent advances now indicate that HIV-1 pathogenesis is likely to result from a
      complex interplay between the virus and the immune system, particularly the
      mechanisms responsible for T cell homeostasis and regeneration. We review these
      data and present a model of HIV-1 pathogenesis in which the protracted loss of
      CD4(+) T cells results from early viral destruction of selected memory T cell
      populations, followed by a combination of profound increases in overall memory T
      cell turnover, damage to the thymus and other lymphoid tissues, and physiological
      limitations in peripheral CD4(+) T cell renewal.

PMID- 12524386
TI  - Toll-like receptors.
AB  - The innate immune system in drosophila and mammals senses the invasion of
      microorganisms using the family of Toll receptors, stimulation of which initiates
      a range of host defense mechanisms. In drosophila antimicrobial responses rely on
      two signaling pathways: the Toll pathway and the IMD pathway. In mammals there
      are at least 10 members of the Toll-like receptor (TLR) family that recognize
      specific components conserved among microorganisms. Activation of the TLRs leads
      not only to the induction of inflammatory responses but also to the development
      of antigen-specific adaptive immunity. The TLR-induced inflammatory response is
      dependent on a common signaling pathway that is mediated by the adaptor molecule
      MyD88. However, there is evidence for additional pathways that mediate TLR ligand
      specific biological responses.

PMID- 12524387
TI  - Regulatory mechanisms that determine the development and function of plasma
      cells.
AB  - Plasma cells are terminally differentiated final effectors of the humoral immune
      response. Plasma cells that result from antigen activation of B-1 and marginal
      zone B cells provide the first, rapid response to antigen. Plasma cells that
      develop after a germinal center reaction provide higher-affinity antibody and
      often survive many months in the bone marrow. Transcription factors Bcl-6 and
      Pax5, which are required for germinal center B cells, block plasmacytic
      differentiation and repress Blimp-1 and XBP-1, respectively. When Bcl-6-dependent
      repression of Blimp-1 is relieved, Blimp-1 ensures that plasmacytic development
      is irreversible by repressing BCL-6 and PAX5. In plasma cells, Blimp-1, XBP-1,
      IRF4, and other regulators cause cessation of cell cycle, decrease signaling from
      the B cell receptor and communication with T cells, inhibit isotype switching and
      somatic hypermutation, downregulate CXCR5, and induce copious immunoglobulin
      synthesis and secretion. Thus, commitment to plasmacytic differentiation involves
      inhibition of activities associated with earlier B cell developmental stages as
      well as expression of the plasma cell phenotype.

PMID- 12524388
TI  - Inflammatory bowel disease in pregnancy.
AB  - Women and men with inflammatory bowel disease (IBD) frequently express concerns
      about fertility and pregnancy. The evidence suggests that women with IBD can
      expect to have a normal pregnancy outcome provided they have inactive disease.
      They have an increased risk of having a small or premature baby but the majority
      will have a normal outcome of pregnancy. The commonly used drugs appear to be
      safe and well tolerated in pregnancy. There remains a need for further studies in
      this area to help in the difficult decisions about the management of IBD around
      the time of conception and during pregnancy.

PMID- 12524389
TI  - Gliadin peptide specific intestinal T cells in coeliac disease.

PMID- 12524390
TI  - Gastrointestinal intraepithelial lymphocytes and T cell lymphomas.

PMID- 12524391
TI  - Hepatic and extrahepatic malignancies and primary sclerosing cholangitis.

PMID- 12524392
TI  - Trypsin and host defence: a new role for an old enzyme.

PMID- 12524393
TI  - European and North American populations should be screened for coeliac disease.

PMID- 12524394
TI  - European and North American populations should be screened for coeliac disease.

PMID- 12524395
TI  - Cyclosporin for refractory ulcerative colitis.

PMID- 12524396
TI  - Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c
      myc by acidified bile acid in vitro.
AB  - BACKGROUND AND AIMS: C-myc over expression is implicated in malignancy although
      to date this has not been studied in Barrett's metaplasia. We sought to determine
      c-myc expression in the malignant progression of Barrett's metaplasia and whether
      it may be induced by bile acids seen in gastro-oesophageal refluxate. METHODS: C
      myc protein and mRNA levels were assessed in 20 Barrett's metaplasia and 20
      oesophageal adenocarcinoma samples by western blotting and real time polymerase
      chain reaction. Levels of c-myc and proliferation were also assessed in cell
      lines OE21, OE33, SW-480, and TE-7 stimulated with pulses or continuous exposure
      to the bile acids deoxycholic acid and chenodeoxycholic acid. RESULTS: C-myc
      protein was upregulated in 50% of Barrett's metaplasia and 90% of oesophageal
      adenocarcinoma samples compared with squamous, gastric, and duodenal controls. C
      myc immunolocalisation in Barrett's metaplasia revealed discrete nuclear
      localisation, becoming more diffuse with progression from low to high grade
      dysplasia to adenocarcinoma. Both continual and pulsed bile acid induced c-myc at
      pH 4, with no effect at pH 7 or with acidified media alone. Pulsed bile acid
      treatment induced proliferation (p<0.05); in contrast, continuous exposure led to
      suppression of proliferation (p<0.05). CONCLUSIONS: We have shown upregulation of
      c-myc with malignant progression of Barrett's metaplasia and suggest that
      acidified bile may be a novel agent responsible for induction of this oncogene.

PMID- 12524397
TI  - Eosinophilic oesophagitis: a novel treatment using Montelukast.
AB  - BACKGROUND: Eosinophilic oesophagitis is a rarely diagnosed condition involving
      eosinophil infiltration of the oesophageal mucosa and creating significant
      symptoms of dysphagia. Failure to diagnose this disorder relates to reluctance to
      biopsy an apparently normal oesophagus. This is essential for histological
      diagnosis. To date, treatment success has been achieved only with
      corticosteroids. We describe here the use of an eosinophil stabilising agent
      Montelukast for the symptomatic relief of these patients. PATIENTS AND METHODS:
      Twelve patients have been identified with this condition in our unit since 1995,
      after thorough investigation of their dysphagia. We commenced eight of these
      patients on the leukotriene receptor antagonist Montelukast to symptomatically
      improve their swallowing while avoiding the use of long term corticosteroids.
      RESULTS: Many of these patients had been previously misdiagnosed, and therefore
      inappropriately and unsuccessfully treated for an extensive period prior to
      referral to our unit. All patients were unresponsive to acid suppression therapy
      alone but showed improvement in their swallowing on Montelukast. Six of eight
      reported complete subjective improvement, five patients remaining completely
      asymptomatic on a maintenance regimen. CONCLUSIONS: Eosinophilic oesophagitis is
      a disease that is often misdiagnosed due to lack of awareness and reluctance of
      clinicians to biopsy an apparently normal oesophagus in dysphagic patients, and
      therefore obtain a histological diagnosis. Investigation of these patients adds
      further evidence to this condition being a separate pathological state from
      gastro-oesophageal reflux and eosinophilic enteritis. Montelukast has been found
      to be of significant help in the symptomatic control of these patients while
      avoiding long term corticosteroids use.

PMID- 12524398
TI  - Risk factors for peptic ulcer disease: a population based prospective cohort
      study comprising 2416 Danish adults.
AB  - BACKGROUND: No population based prospective cohort study has previously assessed
      the impact of multiple risk factors, including Helicobacter pylori infection, on
      the incidence of peptic ulcer disease (PUD). AIMS: To identify risk factors for
      PUD and estimate their relative impact on ulcer incidence. SUBJECTS: Random
      sample of 2416 Danish adults with no history of PU. METHODS: Sample members were
      interviewed in 1982 and 1994. PUs diagnosed within the observation period were
      verified through medical records. Information on psychosocial factors, lifestyle
      practices, and medication was obtained from a questionnaire completed at study
      entry. H pylori infection status was determined by ELISA. RESULTS: The main risk
      factors for PUD were H pylori infection (odds ratio 4.3 (95% confidence interval
      2.2; 8.3)), tobacco smoking (3.8 (1.7; 9.8)), and use of minor tranquillisers
      (3.0 (1.4; 6.6)). Intake of non-steroid anti-inflammatory drugs did not affect
      the incidence of PUD (0.4 (0.1; 2.3)). In those with increased antibodies to H
      pylori, tobacco smoking (12.7 (2.8; 56.8)) and intake of spirits (2.4 (1.1; 5.4))
      increased the risk of PUD whereas moderate leisure time physical activity (0.3
      (0.2; 0.7)) protected against PUD. CONCLUSIONS: Tobacco smoking and H pylori
      infection are the main risk factors for PUD in Danish adults. Physical activity
      may protect against PUD in those infected with H pylori.

PMID- 12524399
TI  - Inflammation and intestinal metaplasia at the squamocolumnar junction in young
      patients with or without Helicobacter pylori infection.
AB  - BACKGROUND: Intestinal metaplasia (IM) in the oesophagus is a known risk factor
      for adenocarcinoma of the oesophagus. The incidence of adenocarcinoma of the
      cardia and oesophagus has increased in Western countries simultaneously with a
      decrease in Helicobacter pylori prevalence. AIMS: To determine the association of
      H pylori infection with inflammation and IM at the squamocolumnar junction (SCJ)
      in young individuals. PATIENTS: A total of 168 (121 women; 72%) consecutive
      outpatients, </=45 years, undergoing gastroscopy, and with no prior H pylori
      eradication treatment. METHODS: Biopsy specimens taken from the antrum, corpus,
      SCJ, and oesophagus were assessed according to the updated Sydney system, and
      type of IM (complete or incomplete) was determined. Serum samples from H pylori
      positive patients were studied for CagA antibodies. RESULTS: In 86% of 37
      patients with gastritis in the antrum and/or corpus (24 histologically H pylori
      positive) and in 23% of 125 patients with a healthy stomach, inflammation was
      present in the glandular mucosa at the SCJ. In the latter, cardiac mucosa more
      often than fundic mucosa at the SCJ was inflamed (p<0.001), the inflammation was
      usually milder in nature, and was associated with signs of reflux disease. IM
      (incomplete or complete) at the SCJ was evident in nine of those 24 with a
      healthy stomach and inflamed cardiac mucosa at the SCJ but in none of those with
      H pylori gastritis. CONCLUSIONS: IM at the SCJ can also appear in young
      individuals in whom it seems to be associated with reflux related isolated
      inflammation in cardiac mucosa at the SCJ but not with H pylori gastritis.

PMID- 12524400
TI  - Missing endomysial and reticulin binding of coeliac antibodies in
      transglutaminase 2 knockout tissues.
AB  - BACKGROUND: Autoantibodies against transglutaminase 2 (TG2) are thought to be
      responsible for the endomysial (EMA), reticulin (ARA), and jejunal antibody (JEA)
      tissue binding of serum samples from coeliac patients but the exclusive role of
      TG2 in these staining patterns has not yet been established. AIMS: To evaluate
      whether antigens other than TG2 contribute to EMA/ARA/JEA reactions. PATIENTS:
      Serum samples from 61 EMA/ARA/JEA positive untreated patients with coeliac
      disease, 40 dermatitis herpetiformis patients, and 34 EMA/ARA/JEA negative non
      coeliac controls were tested. METHODS: TG2 knockout (TG2-/-) and wild-type mouse
      oesophagus, jejunum, liver, and kidney sections, and TG2-/- sections coated with
      human recombinant TG2 were used as substrates in single and double
      immunofluorescent studies for patient IgA binding and tissue localisation of TG2,
      fibronectin, actin, and calreticulin. RESULTS: None of the patient serum samples
      elicited EMA, ARA, or JEA binding in TG2-/- morphologically normal tissues. In
      contrast, 96 of 101 gluten sensitive patient samples (95%) reacted with wild-type
      mouse tissues and all 101 reacted in EMA/ARA/JEA patterns with TG2-/- mouse
      tissues coated with human TG2. Serum IgA binding to TG2-/- smooth muscle cells
      was observed in low titres in 31.1%, 27.5%, and 20.5%, and to TG2-/- epithelium
      in 26.3%, 5.0%, and 8.8% of coeliac, dermatitis herpetiformis, and control
      samples, respectively. These positivities partly colocalised with actin and
      calreticulin but not with TG2 or fibronectin. CONCLUSIONS: EMA/ARA/JEA antibody
      binding patterns are exclusively TG2 dependent both in coeliac and dermatitis
      herpetiformis patients. Actin antibodies are responsible for some positivities
      which are not part of the EMA/ARA/JEA reactions.

PMID- 12524401
TI  - Refractory coeliac sprue is a diffuse gastrointestinal disease.
AB  - BACKGROUND: Refractory coeliac sprue (RCS) with an immunophenotypically aberrant
      clonal intraepithelial lymphocyte (IEL) population is considered a cryptic form
      of intestinal T cell lymphoma. AIMS: To investigate the distribution of the
      abnormal and monoclonal IEL population in the digestive tract of RCS patients.
      PATIENTS AND METHODS: We compared the frequency of lymphocytic gastritis (LG) and
      lymphocytic colitis (LC), together with IEL phenotype and T cell clonality, in
      gastric and colonic samples from 15 adults with RCS (all with aberrant CD3
      intracytoplasmic(+) surface(-) CD8(-) clonal IELs on duodenojejunal biopsies), 18
      patients with active coeliac disease (ACD), and 10 patients with coeliac disease
      (CD) on a gluten free diet (GFD-CD) by means of immunohistochemistry and
      multiplex polymerase chain reaction amplification of the T cell receptor gamma
      gene (TCR-gamma) rearrangement. Blood samples of nine RCS patients were also
      tested for clonality. RESULTS: LG was found in 9/14 (64%), 11/18 (61%), and 3/10
      (30%) patients with RCS, ACD, and GFD-CD, respectively, while LC was found in
      6/11 (55%), 3/4 (75%), and 2/3 (66%) patients. Contrary to CD, all samples from
      patients with LG and LC showed an aberrant IEL phenotype. Monoclonal TCR-gamma
      rearrangements were detected in 8/13 (62%), 8/10 (80%), and 4/9 (44%) of gastric,
      colonic, and blood samples, respectively, from RCS patients, while in CD patients
      such rearrangements were only found in 2/25 (8%) gastric samples. CONCLUSION: The
      immunophenotypically aberrant monoclonal IEL population present in the small
      intestine of patients with RCS frequently disseminates to the blood and the
      entire gastrointestinal epithelium, suggesting that this is a diffuse
      gastrointestinal disease.

PMID- 12524402
TI  - Investigation of the putative immunodominant T cell epitopes in coeliac disease.
AB  - BACKGROUND: Coeliac disease (CD) is an enteropathy mediated by gluten specific T
      cells which secrete interferon gamma (IFN-gamma) when stimulated by gluten
      peptides presented by HLA-DQ2 or DQ8 molecules. Residues 62-75 of alpha(2)
      gliadin have been proposed as the immunodominant epitope in the majority of CD
      patients. Deamidation by tissue transglutaminase (tTG) of the glutamine (Q) at
      position 65 to glutamic acid (E) is essential for T cell stimulation. AIMS: To
      investigate the antigenicity of this peptide and to establish whether its T cell
      activating properties can be downregulated by the formation of altered peptide
      ligands. PATIENTS: Individuals with known CD. METHODS: Peptide G4 corresponding
      to alpha(2) gliadin residues 62-75, Q-E65 and analogues, substituting each amino
      acid, except E65, in turn for alanine residues, were synthesised. Small
      intestinal biopsies were obtained from patients. Biopsies were cultured overnight
      with a peptic/tryptic digest of gliadin (PTG). Lymphocytes were cultured and
      restimulated with tTG treated PTG. A T cell line was cloned and clones tested for
      stimulation and IFN-gamma production in response to G4 and its analogues.
      RESULTS: Some high activity clones were isolated with, for example, a stimulation
      index (SI) of 15 to G4 and secreting 327 pg/ml of IFN-gamma. Substitution of
      amino acids at several positions abolished or downregulated stimulation and IFN
      gamma production. CONCLUSIONS: Peptide G4 is highly immunogenic. Certain amino
      acid substitutions in peptide G4 abolish T cell reactivity while others are
      partial agonists which may have potential in immunomodulation in this condition.

PMID- 12524403
TI  - Early effects of gliadin on enterocyte intracellular signalling involved in
      intestinal barrier function.
AB  - BACKGROUND AND AIMS: Despite the progress made in understanding the immunological
      aspects of the pathogenesis of coeliac disease (CD), the early steps that allow
      gliadin to cross the intestinal barrier are still largely unknown. The aim of
      this study was to establish whether gliadin activates a zonulin dependent
      enterocyte intracellular signalling pathway(s) leading to increased intestinal
      permeability. METHODS: The effect of gliadin on the enterocyte actin cytoskeleton
      was studied on rat intestinal epithelial (IEC-6) cell cultures by fluorescence
      microscopy and spectrofluorimetry. Zonulin concentration was measured on cell
      culture supernatants by enzyme linked immunosorbent assay. Transepithelial
      intestinal resistance (Rt) was measured on ex vivo intestinal tissues mounted in
      Ussing chambers. RESULTS: Incubation of cells with gliadin led to a reversible
      protein kinase C (PKC) mediated actin polymerisation temporarily coincident with
      zonulin release. A significant reduction in Rt was observed after gliadin
      addition on rabbit intestinal mucosa mounted in Ussing chambers. Pretreatment
      with the zonulin inhibitor FZI/0 abolished the gliadin induced actin
      polymerisation and Rt reduction but not zonulin release. CONCLUSIONS: Gliadin
      induces zonulin release in intestinal epithelial cells in vitro. Activation of
      the zonulin pathway by PKC mediated cytoskeleton reorganisation and tight
      junction opening leads to a rapid increase in intestinal permeability.

PMID- 12524404
TI  - Glutamine deprivation facilitates tumour necrosis factor induced bacterial
      translocation in Caco-2 cells by depletion of enterocyte fuel substrate.
AB  - BACKGROUND AND AIMS: Factors that induce luminal bacteria to cross the intestinal
      epithelium following injury remain poorly defined. The aim of this study was to
      investigate the interaction between glutamine metabolism, energy supply, and
      inflammatory mediators in determining the translocation of non-pathogenic
      bacteria across cultured enterocytes. METHODS: The effect of tumour necrosis
      factor alpha (TNF-alpha) on translocation of Escherichia coli C25 across Caco-2
      epithelial monolayers was studied in the presence of products and inhibitors of
      glutamine metabolism. Simultaneous measurements of transepithelial electrical
      resistance (TEER) and flux of lucifer yellow were used to assess effects on the
      paracellular pathway. Lactate dehydrogenase release was used to monitor
      enterocyte integrity. Imaging of monolayers in these experimental conditions was
      undertaken with transmission electron microscopy. RESULTS: Exposure to
      basolateral TNF-alpha (20 ng/ml) for six hours induced translocation of E coli
      across Caco-2 but only if accompanied by simultaneous glutamine depletion
      (p<0.01). Translocation was inhibited by addition of glutamine for two hours
      (p<0.01) but not by an isonitrogenous mixture of non-glutamine containing amino
      acids. Inhibition of glutamine conversion to alpha-ketoglutarate, but not
      blockade of glutathione or polyamine synthesis, also induced translocation in the
      presence of TNF-alpha. Manipulations that induced bacterial translocation were
      associated with a marked reduction in enterocyte ATP levels. No effect of these
      treatments on paracellular permeability or lactate dehydrogenase release was
      observed. Conditions in which translocation occurred were associated with the
      presence of bacteria within enterocyte vacuoles but not the paracellular space.
      CONCLUSIONS: In inflammatory conditions, the availability of glutamine as an
      enterocyte fuel substrate is essential for the preservation of a functional
      barrier to microorganisms. In conditions of acute glutamine depletion, cytokine
      mediated bacterial translocation appears to be primarily a transcellular process.

PMID- 12524405
TI  - Superoxide production and expression of NAD(P)H oxidases by transformed and
      primary human colonic epithelial cells.
AB  - BACKGROUND: Superoxide (O(2)(-)) generation through the activity of reduced
      nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate
      (NADPH) oxidases has been demonstrated in a variety of cell types, but not in
      human colonic epithelial cells. AIMS: To measure O(2)(-) production and effects
      of modulators of NAD(P)H oxidase activity and inhibitors of potential O(2)(-)
      generating enzymes in cultures of human colonic epithelial cells. Expression of
      the catalytic subunits of NAD(P)H oxidase, Nox1 and gp91(phox) (phox, phagocytic
      oxidase), and the membrane bound subunit p22(phox) was assessed. METHODS: The
      transformed colonic epithelial cell lines (DLD-1, HT-29, and Caco-2) were studied
      at subconfluence, confluence, and after differentiation. Primary colonic
      epithelial cells were isolated from mucosal biopsies from the normal human colon.
      Extracellular O(2)(-) production was measured by the cytochrome c reduction assay
      or luminol enhanced luminescence. Nox1, gp91(phox), and p22(phox) mRNA expression
      was assessed in colonic epithelial cells and blood neutrophils by reverse
      transcriptase-polymerase chain reaction. RESULTS: Production rates of O(2)(-)
      were higher in subconfluent transformed cells (mean (SEM) 35.8 (4.2) nmol/mg of
      protein/h) and primary cells (40.4 (5.9)) than in confluent transformed cells
      (6.0 (0.9); p<0.01). The oxidoreductase inhibitor diphenylene iodonium
      significantly inhibited O(2)(-) production whereas NADPH and NADH increased
      production rates. In contrast, O(2)(-) was unaffected by phorbol myristate ester,
      N(G)-nitro-L-arginine methyl ester, indomethacin, or allopurinol. Nox1 mRNA was
      expressed in all colonic epithelial cells whereas gp91(phox) was detected only in
      HT-29 cells and neutrophils. p22(phox) was expressed in all cell types.
      CONCLUSIONS: Cultures of transformed and primary epithelial cells from human
      colon may produce extracellular O(2)(-) through an NAD(P)H oxidase expressing
      Nox1 and p22(phox).

PMID- 12524406
TI  - Alterations of the dominant faecal bacterial groups in patients with Crohn's
      disease of the colon.
AB  - BACKGROUND AND AIMS: The colonic microflora is involved in the pathogenesis of
      Crohn's disease (CD) but less than 30% of the microflora can be cultured. We
      investigated potential differences in the faecal microflora between patients with
      colonic CD in remission (n=9), patients with active colonic CD (n=8), and healthy
      volunteers (n=16) using culture independent techniques. METHODS: Quantitative dot
      blot hybridisation with six radiolabelled 16S ribosomal ribonucleic acid (rRNA)
      targeting oligonucleotide probes was used to measure the proportions of rRNA
      corresponding to each phylogenetic group. Temporal temperature gradient gel
      electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species
      diversity. RESULTS: Enterobacteria were significantly increased in active and
      quiescent CD. Probe additivity was significantly lower in patients (65 (11)% and
      69 (6)% in active CD and quiescent CD) than in healthy controls (99 (7)%). TTGE
      profiles varied markedly between active and quiescent CD but were stable in
      healthy conditions. CONCLUSION: The biodiversity of the microflora remains high
      in patients with CD. Enterobacteria were observed significantly more frequently
      in CD than in health, and more than 30% of the dominant flora belonged to yet
      undefined phylogenetic groups.

PMID- 12524407
TI  - Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a
      Danish cohort study.
AB  - BACKGROUND: 5-Aminosalicylic acid (5-ASA) preparations are the firstline drugs in
      the treatment of inflammatory bowel disease. Data on the safety of these drugs in
      pregnancy are sparse. AIMS: To examine the risk of adverse birth outcome in women
      who were prescribed 5-ASA drugs during pregnancy. PATIENTS: Women were included
      in the study if they were prescribed 5-ASA drugs immediately before or during
      pregnancy. To examine the risk of malformations, we included 60 pregnancies
      exposed to 5-ASA drugs 30 days before pregnancy or in the first trimester. To
      examine stillbirths, preterm births, and low birth weight, we included 88
      pregnancies exposed during the entire pregnancy. Outcomes were compared with
      those of 19 418 pregnancies in which no drugs were prescribed for mothers during
      the study period. METHODS: We conducted a Danish cohort study based on data from
      a population based prescription registry, the Danish Birth Registry, and the
      Hospital Discharge Registry in North Jutland County. RESULTS: Odds ratios for
      malformations, stillbirth, preterm birth, and low birth weight in women who
      received prescriptions for 5-ASA drugs were 1.9 (95% confidence interval 0.7
      5.4), 6.4 (1.7-24.9), 1.9 (0.9-3.9), and 1.2 (0.4-3.3), respectively. The
      increased risk of stillbirth and preterm birth were found only in patients with
      ulcerative colitis. CONCLUSIONS: We found an increased risk of stillbirth and
      preterm birth in women who had been prescribed 5-ASA drugs during pregnancy but
      no substantial increased risk of malformations. It was difficult to distinguish
      the specific effects of disease activity and 5-ASA drugs.

PMID- 12524408
TI  - Budesonide treatment of collagenous colitis: a randomised, double blind, placebo
      controlled trial with morphometric analysis.
AB  - BACKGROUND: Collagenous colitis is characterised by diarrhoea, lymphocytic
      inflammation, and a thickened subepithelial collagen layer in the colorectal
      mucosa. No standard treatment of the disease is established. AIMS: To investigate
      the clinical and histological effect of oral budesonide (Entocort, AstraZeneca)
      in the treatment of collagenous colitis. PATIENTS: Twenty patients with
      collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day
      and/or stool weight >200 g/day). METHODS: A randomised, double blind, placebo
      controlled trial of budesonide treatment. Patients were randomised to placebo or
      budesonide for eight weeks. Stool frequency and stool weight were registered
      before and after treatment. Sigmoidoscopy was performed before and after
      treatment, and biopsies at fixed locations were obtained for morphometric
      analysis. RESULTS: Ten patients were randomised to budesonide and 10 to placebo.
      All 10 patients receiving budesonide had a clinical response compared with two in
      the placebo group (p<0.001). In the budesonide group, stool weight was reduced
      from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to
      1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and
      the thickness of the collagen layer were significantly reduced. A correlation
      between the grade of inflammation as well as collagen layer thickness and stool
      weight was found. No side effects were reported. Eight of 10 patients had relapse
      of symptoms within eight weeks after stopping treatment. CONCLUSIONS: Budesonide
      is a highly effective and well tolerated treatment of collagenous colitis. There
      is a high risk of relapse after stopping eight weeks of treatment.

PMID- 12524410
TI  - Non-steroidal anti-inflammatory drugs as a risk factor for acute diarrhoea: a
      case crossover study.
AB  - BACKGROUND AND AIMS: Several cases of acute colitis induced by non-steroidal anti
      inflammatory drugs (NSAIDs) have been reported but the general role of recent
      NSAID intake as a risk factor for acute diarrhoea has not been studied to date.
      The aim of our study was to determine whether the risk of acute diarrhoea is
      increased by NSAIDs in a prospective series of acute diarrhoea cases which were
      seen by general practitioners in France and were serious enough to require a
      stool culture. Patients, physicians, and methods: A total of 285 consecutive
      patients with acute diarrhoea, seen by Sentinel general practitioners (GPs)
      between December 1998 and July 1999, were enrolled in a case crossover study in
      which each case served as his/her own control. GPs collected information on
      exposure to NSAIDs during the four month period preceding the onset of diarrhoea.
      The relative risk of NSAID related acute diarrhoea was estimated by comparing
      exposure to NSAIDs during a risk period preceding the onset of diarrhoea with
      exposure during the first part of the four month observation period. Three risk
      periods lasting for one, three, and six days before the onset of diarrhoea were
      considered. RESULTS: The relative risks of acute diarrhoea due to recent NSAID
      intake were increased for all three risk periods. These risks and their
      confidence intervals were 2.9 (1.4-6.1) for the one day risk period, 2.7 (1.4
      5.1) for the three day period, and 3.3 (2.0-5.4) for the six day period.
      CONCLUSION: Recent NSAID intake emerges as a risk factor for acute diarrhoea. We
      suggest that acute diarrhoea seen in general practice, and not only acute colitis
      seen by gastroenterologists, should be considered as a potential complication of
      recent NSAID intake.

PMID- 12524409
TI  - The locally acting glucocorticosteroid budesonide enhances intestinal sugar
      uptake following intestinal resection in rats.
AB  - BACKGROUND AND AIMS: Locally and systemically acting corticosteroids alter the
      morphology and transport function of the intestine. This study was undertaken to
      assess the effect of budesonide, prednisone, and dexamethasone on sugar uptake.
      METHODS: Adult male Sprague Dawley rats underwent transection or resection of 50%
      of the middle portion of the small intestine, and in vitro uptake of sugars was
      measured. RESULTS: The 50% enterectomy did not alter jejunal or ileal uptake of
      glucose or fructose. Prednisone had no effect on the uptake of glucose or
      fructose in resected animals. In contrast, in resected rats budesonide increased
      by over 120% the value of the jejunal maximal transport rate for the uptake of
      glucose, and increased by over 150% ileal uptake of fructose. Protein abundance
      and mRNA expression of the sodium dependent glucose transporter in brush border
      membrane (SGLT1), sodium independent fructose transporter in the brush border
      membrane (GLUT5), sodium independent glucose and fructose transporter in the
      basolateral and brush border membranes (GLUT2), and Na(+)/K(+) ATPase alpha1 and
      beta1 did not explain the enhancing effect of budesonide on glucose or fructose
      uptake. Budesonide, prednisone, and dexamethasone reduced jejunal expression of
      the early response gene c-jun. In resected animals, expression of the mRNA of
      ornithine decarboxylase (ODC) in the jejunum was reduced, and corticosteroids
      reduced jejunal expression of the mRNA of proglucagon. CONCLUSIONS: These data
      suggest that the influence of corticosteroids on sugar uptake in resected animals
      may be achieved by post translational processes involving signalling with c-jun,
      ODC, and proglucagon, or other as yet unknown signals. It remains to be
      determined whether budesonide may be useful to stimulate the absorption of sugars
      following intestinal resection in humans.

PMID- 12524411
TI  - A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in
      patients with chronic anal fissures.
AB  - BACKGROUND: Anal fissure is a common painful condition affecting the anal canal.
      The majority of acute fissures heal spontaneously. However, some of these acute
      fissures do not resolve but become chronic. Chronic anal fissures were
      traditionally treated by anal dilation or by lateral sphincterotomy. However,
      both of these surgical treatments may cause a degree of incontinence in up to 30%
      of patients. Several recent trials have shown that nitric oxide donors such as
      glyceryl trinitrate (GTN) can reduce sphincter pressure and heal up to 70% of
      chronic fissures. AIM: This study addressed the dose-response to three different
      concentrations of GTN ointment compared with placebo in a double blind randomised
      controlled trial. METHOD: A double blind, multicentre, randomised controlled
      trial was set up to compare placebo ointment against three active treatment arms
      (0.1%, 0.2%, and 0.4% GTN ointment applied at a dose of 220 mg twice daily) in
      chronic anal fissures. The primary end point was complete healing of the fissure.
      RESULTS: Two hundred patients were recruited over an eight month period from 18
      centres. After eight weeks of treatment the healing rate in the placebo group was
      37.5% compared with 46.9% for 0.1%, 40.4% for 0.2%, and 54.1% for 0.4% GTN. None
      was significantly better than the placebo response. A secondary analysis excluded
      fissures without secondary criteria for chronicity. Healing rates were then found
      to be 24% in the placebo group compared with 50% in the 0.1% GTN group, 36% in
      the 0.2% group, and 57% in the 0.4% GTN group. These values were statistically
      significantly different for the placebo group compared with 0.1% GTN, 0.4% GTN,
      and for the GTN treated group as a whole. CONCLUSIONS: The results of this study
      have demonstrated the significant benefit of topical GTN when applied to patients
      suffering from chronic anal fissures but acute fissures showed a tendency to
      resolve spontaneously. The high proportion of fissures which healed in the
      placebo group suggests that the definition of "chronicity" needs to be
      reassessed. Further studies are required to confirm the optimal therapeutic
      strategy.

PMID- 12524412
TI  - Increased nitric oxide excretion in patients with severe acute pancreatitis:
      evidence of an endotoxin mediated inflammatory response?
AB  - BACKGROUND AND AIMS: Nitric oxide represents a potential key mediator of the
      local and systemic manifestations of acute pancreatitis (AP) in experimental
      models but its role in human disease is uncertain. We therefore sought to assess
      if systemic nitric oxide (NO) production is elevated in severe AP and determine
      whether this is a reflection of biochemical severity or endotoxin exposure.
      PATIENTS AND METHODS: Patients were recruited within 72 hours of pain onset. NO
      derived nitrite excretion determined from a 24 hour sterile urine collection was
      correlated with intestinal macromolecular permeability (polyethylene glycol
      excretion ratio), markers of systemic endotoxin exposure (IgG:IgM endotoxin core
      antibody (EndoCAb) ratio), disease severity, and the magnitude of systemic
      inflammation (peak C reactive protein (CRP) and Acute Physiology and Chronic
      Health Evaluation score II (APACHE-II)). RESULTS: In patients with a severe
      attack (n=20), nitrite excretion was increased significantly compared with
      patients with a mild attack (n=45, 20.6 micro g v 15.65 micro g; p<0.00) and the
      latter with healthy controls (n=20, p=0.004). Nitrite excretion correlated
      strongly with both intestinal permeability (r=0.7, p=0.006) and EndoCAb ratio
      (r=0.7, p<0.01) but not with CRP or APACHE-II scores (p>0.1). CONCLUSIONS: Total
      urinary nitrite excretion is increased in patients with severe AP, and may not be
      simply a reflection of systemic inflammation, but potentially a consequence of
      endotoxin mediated upregulation of inducible NO synthase activity.

PMID- 12524413
TI  - Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for
      extracellular matrix turnover.
AB  - BACKGROUND: Pancreatic fibrosis is a characteristic feature of chronic pancreatic
      injury and is thought to result from a change in the balance between synthesis
      and degradation of extracellular matrix (ECM) proteins. Recent studies suggest
      that activated pancreatic stellate cells (PSCs) play a central role in pancreatic
      fibrogenesis via increased synthesis of ECM proteins. However, the role of these
      cells in ECM protein degradation has not been fully elucidated. AIMS: To
      determine: (i) whether PSCs secrete matrix metalloproteinases (MMPs) and tissue
      inhibitors of metalloproteinases (TIMPs) and, if so (ii) whether MMP and TIMP
      secretion by PSCs is altered in response to known PSC activating factors such as
      tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF
      beta1), interleukin 6 (IL-6), ethanol, and acetaldehyde. METHODS: Cultured rat
      PSCs (n=3-5 separate cell preparations) were incubated at 37 degrees C for 24
      hours with serum free culture medium containing TNF-alpha (5-25 U/ml), TGF-beta1
      (0.5-1 ng/ml), IL-6 (0.001-10 ng/ml), ethanol (10-50 mM), or acetaldehyde (150
      200 micro M), or no additions (controls). Medium from control cells was examined
      for the presence of MMPs by zymography using a 10% polyacrylamide-0.1% gelatin
      gel. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine
      gene expression of MMP9 and the tissue inhibitors of metalloproteinases TIMP1 and
      TIMP2. Western blotting was used to identify a specific MMP, MMP2 (a gelatinase
      that digests basement membrane collagen and the dominant MMP observed on
      zymography) and a specific TIMP, TIMP2. Reverse zymography was used to examine
      functional TIMPs in PSC secretions. The effect of TNF-alpha, TGF-beta1, and IL-6
      on MMP2 secretion was assessed by densitometry of western blots. The effect of
      ethanol and acetaldehyde on MMP2 and TIMP2 secretion was also assessed by this
      method. RESULTS: Zymography revealed that PSCs secrete a number of MMPs including
      proteinases with molecular weights consistent with MMP2, MMP9, and MMP13. RT-PCR
      demonstrated the presence of mRNA for metalloproteinase inhibitors TIMP1 and
      TIMP2 in PSCs while reverse zymography revealed the presence of functional TIMP2
      in PSC secretions. MMP2 secretion by PSCs was significantly increased by TGF
      beta1 and IL-6, but was not affected by TNF-alpha. Ethanol and acetaldehyde
      induced secretion of both MMP2 and TIMP2 by PSCs. CONCLUSIONS: Pancreatic
      stellate cells have the capacity to synthesise a number of matrix
      metalloproteinases, including MMP2, MMP9, and MMP13 and their inhibitors TIMP1
      and TIMP2. MMP2 secretion by PSCs is significantly increased on exposure to the
      proinflammatory cytokines TGF-beta1 and IL-6. Both ethanol and its metabolite
      acetaldehyde increase MMP2 as well as TIMP2 secretion by PSCs. IMPLICATION: The
      role of pancreatic stellate cells in extracellular matrix formation and
      fibrogenesis may be related to their capacity to regulate the degradation as well
      as the synthesis of extracellular matrix proteins.

PMID- 12524414
TI  - Long term histological improvement and clearance of intrahepatic hepatitis C
      virus RNA following sustained response to interferon-ribavirin combination
      therapy in liver transplanted patients with hepatitis C virus recurrence.
AB  - BACKGROUND AND AIMS: A proportion of liver transplanted patients with recurrent
      chronic hepatitis have a sustained virological response to combination therapy
      with interferon plus ribavirin. However, the long term benefit of antiviral
      therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in
      patients with HCV recurrence. This study examined the long term biochemical,
      virological, and histological outcome in transplanted patients with recurrent
      chronic hepatitis who had a sustained virological response to antiviral therapy.
      PATIENTS AND METHODS: Fifty four patients with recurrent hepatitis C were treated
      with antiviral therapy involving induction by combination therapy (interferon
      (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12
      months. Fourteen patients who had recurrent chronic hepatitis and sustained
      virological response to antiviral therapy were followed for three years after the
      end of antiviral therapy. Serum alanine aminotransferases were assessed every
      three months during the observation period. Serum hepatitis C RNA detected by
      polymerase chain reaction was evaluated every six months during follow up, and
      protocol biopsy procedures were performed routinely every year. Semiquantitative
      histopathological assessment of allograft hepatitis was performed using the
      Knodell score and HCV was also detected by polymerase chain reaction on frozen
      graft tissue samples. RESULTS: At the end of antiviral therapy, the sustained
      response rate was 26%. A complete response (normal serum alanine aminotransferase
      level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three
      years after the end of treatment. A comparison of liver histology findings before
      and after a mean of three years after antiviral therapy showed a clear
      improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy
      showed normal or near normal histological findings. After three years of follow
      up, the total Knodell score was 3.2 (range 1-8) versus 8.3 (range 5-12) before
      treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14
      patients and was undetectable at the end of follow up in 13/14 (93%) patients
      tested. CONCLUSION: In patients with biochemical and virological responses
      induced by ribavirin and interferon, a complete response was sustained in 93% for
      at least three years after cessation of therapy. This long term response was
      associated with absence of detectable intrahepatic hepatitis C RNA and marked
      histological improvement.

PMID- 12524415
TI  - Worsening of steatosis is an independent factor of fibrosis progression in
      untreated patients with chronic hepatitis C and paired liver biopsies.
AB  - BACKGROUND AND AIMS: Steatosis, a frequent histological finding in patients with
      chronic hepatitis C (CHC), has been suggested to influence liver fibrosis
      progression. The aim of the present study was to evaluate in patients with CHC
      and paired liver biopsies the relationship between the evolution of steatosis and
      that of fibrosis between the two biopsies. METHODS: Ninety six patients were
      selected according to the following criteria: absence of treatment; absence of
      cirrhosis at initial biopsy; and serum hepatitis B surface antigen and human
      immunodeficiency virus antibody negativity. Degrees of necroinflammatory
      activity, fibrosis, and steatosis grades were assessed in the two biopsies. In
      addition to histological lesions, parameters studied included the source of
      infection, duration of infection, body mass index, alcohol intake, alanine
      aminotransferase levels, hepatitis C virus genotype, and viral load. RESULTS: The
      mean interval between the two biopsies was 48 (32) months. Steatosis was found in
      54% of patients at first biopsy, and was severe in 9%. Worsening of steatosis was
      observed in 34% of patients, stability in 50%, and improvement in 16%. Worsening
      of steatosis was significantly associated with hepatic fibrosis progression in
      patients with (p=0.03) or without (p<0.03) steatosis at diagnosis. Overall,
      fibrosis progression was observed in 31% of patients and stability in 69%. In a
      univariate analysis, fibrosis progression was associated with male sex (p=0.05),
      worsening of histological activity (p=0.04), and worsening of steatosis
      (p=0.0003). In a multivariate analysis, the only factor independently associated
      with fibrosis progression was worsening of steatosis (worsening v
      improvement/stability: odds ratio 4.7 (95% confidence interval 1.3-10.8);
      p=0.0001). CONCLUSIONS: Our results suggest that in untreated patients with CHC
      and serial liver biopsies, fibrosis progression is strongly associated with
      worsening of steatosis.

PMID- 12524416
TI  - Effect of neonatal capsaicin treatment on haemodynamics and renal function in
      cirrhotic rats.
AB  - BACKGROUND: Mechanisms underlying abnormalities of circulation and renal function
      in cirrhosis are not completely understood. Our previous study revealed that
      primary afferent denervation by neonatal capsaicin treatment prevented the
      development of hyperdynamic circulation in portal hypertensive and cirrhotic
      rats. AIMS: The present study aimed to clarify the role of capsaicin sensitive
      nerves in the development of renal dysfunction and ascites formation in
      cirrhosis. METHODS: Rat pups were injected with capsaicin (50 mg/kg) or vehicle
      and allowed to grow. When they reached adulthood, cirrhosis was induced by bile
      duct ligation while controls received sham operation. Cardiac output and regional
      blood flows were measured by radioactive microspheres, glomerular filtration rate
      by (3)H inulin clearance, and urine volume, sodium excretion, and ascites
      formation were determined. Immunohistochemical staining for Fos in the brain stem
      cardiovascular regulatory nuclei, the nucleus of the solitary tract, and
      ventrolateral medulla was measured as an index of central neuronal activation.
      RESULTS: Increased cardiac output and renal blood flow, and decreased systemic
      vascular resistance, arterial pressure, renal vascular resistance, and glomerular
      filtration rate, as well as ascites, were found in vehicle treated cirrhotic
      rats. Neonatal capsaicin treatment completely blocked the development of
      hyperdynamic circulation and ascites, and improved renal function in cirrhotic
      rats. This was associated with complete abrogation of brain stem neuronal
      activation in capsaicin treated cirrhotic rats. CONCLUSIONS: These results
      indicate that intact primary afferent innervation is necessary for the
      development of not only the hyperdynamic circulation but also the renal
      dysfunction and ascites formation characteristic of cirrhosis.

PMID- 12524417
TI  - Antidepressant induced cholestasis: hepatocellular redistribution of multidrug
      resistant protein (MRP2).
AB  - BACKGROUND: We report two cases of antidepressant induced cholestasis. CASE
      REPORTS: We describe the first reported case of acute cholestasis due to
      citalopram (selective serotonin reuptake inhibitor) occurring in a patient who
      also experienced obstetric cholestasis in association with each of three
      pregnancies; in a second patient cholestasis developed due to dothiepin
      (tricyclic antidepressant), and six years later due to paroxetine. In both cases
      liver biopsies showed features of a "pure" cholestasis with total resolution
      within 1-6 months after withdrawal of the causative drug. Immunostaining for the
      canalicular transporter, multidrug resistant protein 2 (MRP2), responsible for
      biliary secretion of several organic anions including bilirubin glucuronides,
      showed sustained expression in both biopsies as well as relocalisation with
      appearance of strong staining of the basolateral membrane of the hepatocyte. This
      finding has also not been reported previously. CONCLUSIONS: We postulate that
      intracellular redistribution of MRP2 may reflect an adaptive compensatory
      mechanism which helps in the elimination of the drug or its cholestatic
      metabolites from the hepatocyte back to the sinusoidal space and subsequent
      excretion in urine. Changes seen in these two patients differ from findings
      previously reported in rats where downregulation of mrp2 occurs in response to
      experimentally induced cholestasis. We speculate that the rat is more advanced
      than humans in its ability to downregulate canalicular transporter expression as
      protection against progressive intrahepatic cholestasis.

PMID- 12524418
TI  - A novel case with germline p53 gene mutation having concurrent multiple primary
      colon tumours.
AB  - During a search for causative genes in patients with concurrent multiple primary
      colon tumours, we found a novel case with a germline mutation of the p53 gene,
      from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that
      this patient had, one large advanced carcinoma exhibited a somatic p53 mutation
      and a somatic APC mutation, in addition to the germline p53 mutation. Two early
      carcinomas and three adenomas had somatic APC mutations but no somatic p53
      mutation or loss of the p53 allele. K-ras-2 mutations were detected in an
      advanced carcinoma and an early carcinoma. The present results suggest that a
      patient with a certain type of germline p53 mutation is predisposed to concurrent
      multiple colon tumours. It is also suggested that in such a patient, a somatic
      APC mutation is involved in tumour formation and that an additional somatic p53
      mutation contributes to tumour progression.

PMID- 12524420
TI  - Bleeding peptic ulcer.

PMID- 12524419
TI  - Dendritic cells and immune regulation in the liver.
AB  - Hepatic dendritic cells (DC) unquestionably play important roles in the induction
      and regulation of immune responses. Due to their paucity, functional
      characterisation of these important antigen presenting cells has been slow but
      use of DC growth factors (in particular GM-CSF and Flt3L) that markedly enhance
      their numbers has proved helpful in furnishing adequate study material. While
      there is growing evidence that DC function is affected in the pathogenesis of
      liver disease, most work to date has been performed on non-hepatic DC. Increasing
      knowledge of hepatic DC biology is likely to improve our understanding of disease
      pathogenesis and resistance to and therapy of liver disease.

PMID- 12524421
TI  - Selective binding and oligomerization of the murine granulocyte colony
      stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.
AB  - Granulocyte colony-stimulating factor regulates neutrophil production by binding
      to a specific receptor, the granulocyte colony-stimulating factor receptor,
      expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte
      colony-stimulating factor are used clinically to treat neutropenias. As part of
      an effort to develop granulocyte colony-stimulating factor mimics with the
      potential for oral bioavailability, we previously identified a nonpeptidyl small
      molecule (SB-247464) that selectively activates murine granulocyte colony
      stimulating factor signal transduction pathways and promotes neutrophil formation
      in vivo. To elucidate the mechanism of action of SB-247464, a series of cell
      based and biochemical assays were performed. The activity of SB-247464 is
      strictly dependent on the presence of zinc ions. Titration microcalorimetry
      experiments using a soluble murine granulocyte colony-stimulating factor receptor
      construct show that SB-247464 binds to the extracellular domain of the receptor
      in a zinc ion-dependent manner. Analytical ultracentrifugation studies
      demonstrate that SB-247464 induces self-association of the N-terminal three
      domain fragment in a manner that is consistent with dimerization. SB-247464
      induces internalization of granulocyte colony-stimulating factor receptor on
      intact cells, consistent with a mechanism involving receptor oligomerization.
      These data show that small nonpeptidyl compounds are capable of selectively
      binding and inducing productive oligomerization of cytokine receptors.

PMID- 12524422
TI  - A G protein-coupled receptor responsive to bile acids.
AB  - So far some nuclear receptors for bile acids have been identified. However, no
      cell surface receptor for bile acids has yet been reported. We found that a novel
      G protein-coupled receptor, TGR5, is responsive to bile acids as a cell-surface
      receptor. Bile acids specifically induced receptor internalization, the
      activation of extracellular signal-regulated kinase mitogen-activated protein
      kinase, the increase of guanosine 5'-O-3-thio-triphosphate binding in membrane
      fractions, and intracellular cAMP production in Chinese hamster ovary cells
      expressing TGR5. Our quantitative analyses for TGR5 mRNA showed that it was
      abundantly expressed in monocytes/macrophages in human and rabbit. Treatment with
      bile acids was found to suppress the functions of rabbit alveolar macrophages
      including phagocytosis and lipopolysaccharide-stimulated cytokine productions. We
      prepared a monocytic cell line expressing TGR5 by transfecting a TGR5 cDNA into
      THP-1 cells that did not express TGR5 originally. Treatment with bile acids
      suppressed the cytokine productions in the THP-1 cells expressing TGR5, whereas
      it did not influence those in the original THP-1 cells, suggesting that TGR5 is
      implicated in the suppression of macrophage functions by bile acids.

PMID- 12524423
TI  - Protection of islets by in situ peptide-mediated transduction of the Ikappa B
      kinase inhibitor Nemo-binding domain peptide.
AB  - We have previously demonstrated that adenoviral gene transfer of the NF-kappaB
      inhibitor IkappaB to human islets results in protection from interleukin (IL)
      1beta-mediated dysfunction and apoptosis. Here we report that human and mouse
      islets can be efficiently transduced by a cationic peptide transduction domain
      (PTD-5) without impairment of islet function. PTD mediated delivery of a peptide
      inhibitor of the IL-1beta-induced IkappaB kinase (IKK), derived from IKKbeta
      (NBD; Nemo-binding domain), and completely blocked the detrimental effects of IL
      1beta on islet function and NF-kappaB activity, in a similar manner to Ad
      IkappaB. We also demonstrate that mouse islets can be transduced in situ by
      infusion of the transduction peptide through the bile duct prior to isolation,
      resulting in 40% peptide transduction of the beta-cells. Delivery of the IKK
      inhibitor transduction fusion peptide (PTD-5-NBD) in situ to mouse islets
      resulted in improved islet function and viability after isolation. These results
      demonstrate the feasibility of using PTD-mediated delivery to transiently modify
      islets in situ to improve their viability and function during isolation, prior to
      transplantation.

PMID- 12524424
TI  - Transforming growth factor-beta inhibits adipocyte differentiation by Smad3
      interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP
      transactivation function.
AB  - Transforming growth factor (TGF)-beta is a potent inhibitor of adipocyte
      differentiation. To identify which adipocyte transcription factors might be
      targeted by TGF-beta, we overexpressed key adipogenic transcription factors,
      C/EBPbeta, C/EBPdelta, or peroxisome proliferator-activated receptor (PPAR) gamma
      in NIH3T3 cells and tested the ability of TGF-beta to block adipogenesis. We show
      that TGF-beta inhibits adipocyte differentiation driven by either C/EBPbeta or
      C/EBPdelta without affecting C/EBP protein expression levels, suggesting that
      these C/EBPs are a direct target of TGF-beta action. Because TGF-beta inhibits
      adipogenesis by signaling through Smad3, we examined physical and functional
      interactions of Smad3 and Smad4 with C/EBPbeta, C/EBPdelta, and PPARgamma2.
      C/EBPbeta and C/EBPdelta were found to physically interact with Smad3 and Smad4,
      and Smad3 cooperated with Smad4 and TGF-beta signaling to repress the
      transcriptional activity of C/EBPs. Thus, repression of the activity of C/EBPs by
      Smad3/4 at C/EBP binding sites inhibited transcription from the PPARgamma2 and
      leptin promoters. In contrast, PPARgamma interacted only very weakly with Smad3
      and its transcriptional activity was not repressed by Smad3/4 or in response to
      TGF-beta. Smad3/4 did not reduce the ability of C/EBP to bind to its cognate DNA
      sequence, but repressed transcription by inhibiting the transactivation function
      of C/EBP.

PMID- 12524425
TI  - RhoA expression is controlled by nitric oxide through cGMP-dependent protein
      kinase activation.
AB  - The small G protein RhoA is a convergence point for multiple signals that
      regulate smooth muscle cell functions. NO plays a major role in the structure and
      function of the normal adult vessel wall, mainly through modulation of gene
      transcription. This study was thus performed to analyze in vitro and in vivo the
      effect of NO signaling on RhoA expression in arterial smooth muscle cells. In rat
      or human artery smooth muscle cells, sodium nitroprusside or 8-(2
      chlorophenylthio)-cGMP induced a rise in RhoA mRNA and protein expression, which
      was inhibited by the cGMP-dependent protein kinase (PKG) inhibitor (R(p))-8-bromo
      beta-phenyl-1,N(2)-ethenoguanosine 3':5'-phosphorothioate. The NO/PKG stimulation
      of RhoA expression involved both an increase in RhoA protein stability and
      stimulation of rhoA gene transcription. Cloning and functional analysis of the
      human rhoA promoter revealed that the effect of NO/PKG involved phosphorylation
      of ATF-1 and subsequent binding to the cAMP-response element. Chronic inhibition
      of NO synthesis in N(omega)-nitro-l-arginine-treated rats induced a strong
      decrease in RhoA mRNA and protein expression in aorta and pulmonary artery
      associated with inhibition of RhoA-mediated Ca(2+) sensitization. These effects
      were prevented by oral administration of the cGMP phosphodiesterase inhibitor
      sildenafil. These results show that NO/PKG signaling positively controls RhoA
      expression and suggest that the basal release of NO is necessary to maintain RhoA
      expression and RhoA-dependent functions in vascular smooth muscle cells.

PMID- 12524426
TI  - Organic atmospheric particulate material.
AB  - Carbonaceous compounds comprise a substantial fraction of atmospheric particulate
      matter (PM). Particulate organic material can be emitted directly into the
      atmosphere or formed in the atmosphere when the oxidation products of certain
      volatile organic compounds condense. Such products have lower volatilities than
      their parent molecules as a result of the fact that adding oxygen and/or nitrogen
      to organic molecules reduces volatility. Formation of secondary organic PM is
      often described in terms of a fractional mass yield, which relates how much PM is
      produced when a certain amount of a parent gaseous organic is oxidized. The
      theory of secondary organic PM formation is outlined, including the role of
      water, which is ubiquitous in the atmosphere. Available experimental studies on
      secondary organic PM formation and molecular products are summarized.

PMID- 12524427
TI  - State-resolved dynamics of photofragmentation.
AB  - We discuss experiments on the dynamics of photodissociation that employ methods
      to select the energy, sometimes quantum states, of the reactant and to determine
      the quantum states and energy, sometimes also the orientation and alignment, of
      products. A summary of new advances of experimental methods is followed by
      applications to photodissociation of various types. Representative examples of
      simple bond fission, molecular elimination, and three-body dissociation with
      determined electronic states-sometimes the orientation of their angular momentum
      of product atoms or distributions of electronic and internal states of product
      molecules illustrate the detailed information and insight that one can derive
      from such experiments. Photodissociation of van der Waals complexes, ions,
      species adsorbed on surfaces, and species in solution is excluded from this
      review.

PMID- 12524428
TI  - Femtosecond time-resolved photoelectron spectroscopy of polyatomic molecules.
AB  - Femtosecond time-resolved photoelectron spectroscopy is emerging as a useful
      technique for investigating excited state dynamics in isolated polyatomic
      molecules. The sensitivity of photoelectron spectroscopy to both electronic
      configurations and vibrational dynamics makes it well suited to the study of
      ultrafast nonadiabatic processes. We review the conceptual interpretation of
      wavepacket dynamics experiments, emphasizing the role of the final state. We
      discuss the advantages of the molecular ionization continuum as the final state
      in polyatomic wavepacket experiments and show how the electronic structure of the
      continuum can be used to disentangle electronic from vibrational dynamics. We
      illustrate these methods with examples from diatomic wavepacket dynamics,
      internal conversion in polyenes and polyaromatic hydrocarbons, excited state
      intramolecular proton transfer, and azobenzene photoiosomerization dynamics.

PMID- 12524429
TI  - Conjugated polymers as molecular materials: how chain conformation and film
      morphology influence energy transfer and interchain interactions.
AB  - The electronic structure of conjugated polymers is of current interest because of
      the wide range of potential applications for such materials in optoelectronic
      devices. It is increasingly clear that the electronic properties of conjugated
      polymers depend sensitively on the physical conformation of the polymer chains
      and the way the chains pack together in films. This article reviews the evidence
      that interchain electronic species do form in conjugated polymer films, and that
      their number and chemical nature depend on processing conditions; the chain
      conformation, degree of interchain contact, and rate of energy transfer can be
      controlled by factors such as choice of solvent, polymer concentration, thermal
      annealing, presence of electrically charged side groups, and encapsulation of the
      polymer chains in mesoporous silica. Taken together, the results reconcile many
      contradictions in the literature and provide a prescription for the optimization
      of conjugated polymer film morphology for device applications.

PMID- 12524430
TI  - Rough and rocky road to the retinoid revolution.
AB  - Some of us who were born in the middle of Europe between World Wars I and II had
      to face quite a few unusual challenges that we all met in different ways. I was
      born and raised in Prague, Czechoslovakia, a country at the time of my birth that
      was governed by a Western style of democracy, which was later destroyed by the
      occupation by Nazi Germany and subsequently by the takeover by the equally cruel
      Communists. Life required special means of adaptation to the changing living
      conditions and a great deal of luck to survive. After graduating from the School
      of Technology, I started working in the Department of Medicine at Charles
      University in Prague as a clinical chemist in endocrinology. This work was
      followed with training in basic biochemistry and the study of metabolic changes
      in stress. This rather diversified research, due to my changing of workplaces,
      led to the findings that diet can change enzymatic activity of liver tryptophan
      oxygenase. For a short time I worked on the metabolism of cyclic AMP in
      Escherichia coli, and at the age of 41, I made a risky move and succeeded in
      escaping with my family from the "paradise of communism." The reasons for this
      decision will become clear. After settling in the United States, I worked on the
      mechanism of activation of liver tryptophan oxygenase by cyclic AMP and
      eventually moved to the Vanderbilt University School of Medicine. There I
      initially worked on the mechanism of action of steroid hormones and finally on
      the molecular mechanism of action of retinoids, retinol, and retinoic acid. Also
      in cooperation with neonatologists, I initiated studies on prematurely born human
      neonates which led to successful supplementation of these patients with vitamin
      A. The work from my laboratory and my coworkers eventually became recognized.

PMID- 12524431
TI  - Mechanism and regulation of selenoprotein synthesis.
AB  - Selenium is an essential trace element that is incorporated into proteins as
      selenocysteine (Sec), the twenty-first amino acid. Sec is encoded by a UGA codon
      in the selenoprotein mRNA. The decoding of UGA as Sec requires the reprogramming
      of translation because UGA is normally read as a stop codon. The translation of
      selenoprotein mRNAs requires cis-acting sequences in the mRNA and novel trans
      acting factors dedicated to Sec incorporation. Selenoprotein synthesis in vivo is
      highly selenium-dependent, and there is a hierarchy of selenoprotein expression
      in mammals when selenium is limiting. This review describes emerging themes from
      studies on the mechanism, kinetics, and efficiency of Sec insertion in
      prokaryotes. Recent developments that provide mechanistic insight into how the
      eukaryotic ribosome distinguishes between UGA/Sec and UGA/stop codons are
      discussed. The efficiency and regulation of mammalian selenoprotein synthesis are
      considered in the context of current models for Sec insertion.

PMID- 12524432
TI  - Deciphering the genetic basis of speech and language disorders.
AB  - A significant number of individuals have unexplained difficulties with acquiring
      normal speech and language, despite adequate intelligence and environmental
      stimulation. Although developmental disorders of speech and language are
      heritable, the genetic basis is likely to involve several, possibly many,
      different risk factors. Investigations of a unique three-generation family
      showing monogenic inheritance of speech and language deficits led to the
      isolation of the first such gene on chromosome 7, which encodes a transcription
      factor known as FOXP2. Disruption of this gene causes a rare severe speech and
      language disorder but does not appear to be involved in more common forms of
      language impairment. Recent genome-wide scans have identified at least four
      chromosomal regions that may harbor genes influencing the latter, on chromosomes
      2, 13, 16, and 19. The molecular genetic approach has potential for dissecting
      neurological pathways underlying speech and language disorders, but such
      investigations are only just beginning.

PMID- 12524434
TI  - Topology models for 37 Saccharomyces cerevisiae membrane proteins based on C
      terminal reporter fusions and predictions.
AB  - We provide experimentally based topology models for 37 integral membrane proteins
      from Saccharomyces cerevisiae. A C-terminal fusion to a dual Suc2/His4C topology
      reporter has been used to determine the location of the C terminus of each
      protein relative to the endoplasmic reticulum membrane, and this information is
      used in conjunction with theoretical topology prediction methods to arrive at a
      final topology model. We propose that this approach may be used to produce
      reliable topology models on a proteome-wide scale.

PMID- 12524433
TI  - The recycling of apolipoprotein E in primary cultures of mouse hepatocytes.
      Evidence for a physiologic connection to high density lipoprotein metabolism.
AB  - Internalization of apoE-containing very low density protein (VLDL) by hepatocytes
      in vivo and in vitro leads to apoE recycling and resecretion. Because of the role
      of apoE in VLDL metabolism, apoE recycling may influence lipoprotein assembly or
      remnant uptake. However, apoE is also a HDL protein, and apoE recycling may be
      related to reverse cholesterol transport. To investigate apoE recycling, apoE(-/
      ) mouse hepatocytes were incubated (pulsed) with wild-type mouse lipoproteins,
      and cells and media were collected at chase periods up to 24 h. When cells were
      pulsed with VLDL, apoE was resecreted within 30 min. Although the mass of apoE in
      the media decreased with time, it could be detected up to 24 h after the pulse.
      Intact intracellular apoE was also detectable 24 h after the pulse. ApoE was also
      resecreted when cells were pulsed with HDL. When apoA-I was included in the chase
      media after a pulse with VLDL, apoE resecretion increased 4-fold. Furthermore,
      human apoE was resecreted from wild-type mouse hepatocytes after a pulse with
      human VLDL. Finally, apoE was resecreted from mouse peritoneal macrophages after
      pulsing with VLDL. We conclude that 1) HDL apoE recycles in a quantitatively
      comparable fashion to VLDL apoE; 2) apoE recycling can be modulated by
      extracellular apoA-I but is not affected by endogenous apoE; and 3) recycling
      occurs in macrophages as well as in hepatocytes, suggesting that the process is
      not cell-specific.

PMID- 12524435
TI  - The isolated N-terminal domain of the glucagon-like peptide-1 (GLP-1) receptor
      binds exendin peptides with much higher affinity than GLP-1.
AB  - Two fragments of the receptor for glucagon-like peptide-1 (GLP-1), each
      containing the N-terminal domain, were expressed and characterized in either
      bacterial or mammalian cells. The first fragment, rNT-TM1, included the N
      terminal domain and first transmembrane helix and was stably expressed in the
      membrane of human embryonic kidney 293 cells. The second, 6H-rNT, consisted of
      only the N-terminal domain of the receptor fused with a polyhistidine tag at its
      N terminus. The latter fragment was expressed in Escherichia coli in the form of
      inclusion bodies from which the protein was subsequently purified and refolded in
      vitro. Although both receptor fragments displayed negligible (125)I-labeled GLP
      1(7-36)amide-specific binding, they both displayed high affinity for the
      radiolabeled peptide antagonist (125)I-exendin-4(9-39). Competition binding
      studies demonstrated that the N-terminal domain of the GLP-1 receptor maintains
      high affinity for the agonist exendin-4 as well as the antagonists exendin-4(3
      39) and exendin-4(9-39) whereas, in contrast, GLP-1 affinity was greatly reduced.
      This study shows that although the exendin antagonists are not dependent upon the
      extracellular loops and transmembrane helices for maintaining their normal high
      affinity binding, the endogenous agonist GLP-1 requires regions outside of the N
      terminal domain. Hence, distinct structural features in exendin-4, between
      residues 9 and 39, provide additional affinity for the N-terminal domain of the
      receptor. These data are consistent with a model for the binding of peptide
      ligands to the GLP-1 receptor in which the central and C-terminal regions of the
      peptides bind to the N terminus of the receptor, whereas the N-terminal residues
      of peptide agonists interact with the extracellular loops and transmembrane
      helices.

PMID- 12524436
TI  - Distinct sites regulating grayanotoxin binding and unbinding to D4S6 of Na(v)1.4
      sodium channel as revealed by improved estimation of toxin sensitivity.
AB  - Grayanotoxin (GTX) exerts selective effects on voltage-dependent sodium channels
      by eliminating fast sodium inactivation and causing a hyperpolarizing shift in
      voltage dependence of channel activation. In this study, we adopted a newly
      developed protocol that provides independent estimates of the binding and
      unbinding rate constants of GTX (k(on) and k(off)) to GTX sites on the sodium
      channel protein, important in the molecular analysis of channel modification.
      Novel GTX sites were determined in D2S6 (Asn-784) and D3S6 (Ser-1276) by means of
      site-directed mutagenesis; the results suggested that the GTX receptor consists
      of the S6 transmembrane segments of four homologous domains facing the ion
      conducting pore. We systematically introduced at two sites in D4S6 (Na(v)1.4-Phe
      1579 and Na(v)1.4-Tyr-1586) amino acid substituents with residues containing
      hydrophobic, aromatic, charged, or polar groups. Generally, substitutions at Phe
      1579 increased both k(on) and k(off), resulting in no prominent change in
      dissociation constant (K(d)). It seems that the smaller the molecular size of the
      residue at Na(v)1.4-Phe-1579, the larger the rates of k(on) and k(off),
      indicating that this site acts as a gate regulating access of toxin molecules to
      a receptor site. Substitutions at Tyr-1586 selectively increased k(off) but had
      virtually no effect on k(on), thus causing a drastic increase in K(d). At
      position Tyr-1586, a hydrophobic or aromatic amino acid side chain was required
      to maintain normal sensitivity to GTX. These results suggest that the residue at
      position Tyr-1586 has a more critical role in mediating GTX binding than the one
      at position Phe-1579. Here, we propose that the affinity of GTX to Na(v)1.4
      sodium channels might be regulated by two residues (Phe and Tyr) at positions Phe
      1579 and Tyr-1586, which, respectively, control access and binding of GTX to its
      receptor.

PMID- 12524437
TI  - Neutrophil cathepsin G promotes prothrombinase and fibrin formation under flow
      conditions by activating fibrinogen-adherent platelets.
AB  - Human neutrophil proteases cathepsin G and elastase can directly alter platelet
      function and/or participate in coagulation cascade reactions on the platelet or
      neutrophil surface to enhance fibrin formation. The clotting of recalcified
      platelet-free plasma (PFP) or platelet-rich plasma (PRP) supplemented with corn
      trypsin inhibitor (to shut down contact activation) was studied in well-plates or
      flow assays. Inhibitors of cathepsin G or elastase significantly delayed the
      burst time (t(50)) of thrombin generation in neutrophil-supplemented PRP from 49
      min to 59 and 77 min, respectively, in well-plate assays as well as reduced
      neutrophil-promoted fibrin deposition on fibrinogen-adherent platelets under flow
      conditions. In flow assays, purified cathepsin G was a far more potent activator
      of platelet-dependent coagulation than elastase. Anti-tissue factor had no effect
      on neutrophil protease-enhanced thrombin formation in PRP. The addition of
      cathepsin G (425 nm) or convulxin (10 nm) to PRP dramatically reduced the t(50)
      of thrombin generation from 53 min to 17 or 23 min, respectively. In contrast,
      the addition of elastase to PRP left the t(50) unaltered. Whereas perfusion of
      PFP (gamma(w) = 62.5 s(-1)) over fibrinogen-adherent platelets did not result in
      fibrin formation until 50 min, massive fibrin could be observed on cathepsin G
      treated platelets even at 35 min. Cathepsin G addition to corn trypsin inhibitor
      treated PFP produced little thrombin unless anionic phospholipid was present.
      However, further activation inhibition studies indicated that cathepsin G
      enhances fibrin deposition under flow conditions by elevating the activation
      state of fibrinogen-adherent platelets rather than by cleaving coagulation
      factors.

PMID- 12524438
TI  - Identification and functional analysis of two Ca2+-binding EF-hand motifs in the
      B"/PR72 subunit of protein phosphatase 2A.
AB  - Protein phosphatase 2A (PP2A) is a multifunctional serine/threonine phosphatase
      that is critical to many cellular processes including cell cycle regulation and
      signal transduction. PP2A is a heterotrimer containing a structural (A) and
      catalytic (C) subunit, associated with one variable regulatory or targeting B
      type subunit, of which three families have been described to date (B/PR55,
      B'/PR61, and B"/PR72). We identified two functional and highly conserved Ca(2+)
      binding EF-hand motifs in human B"/PR72 (denoted EF1 and EF2), demonstrating for
      the first time the ability of Ca(2+) to interact directly with and regulate PP2A.
      EF1 and EF2 apparently bind Ca(2+) with different affinities. Ca(2+) induces a
      significant conformational change, which is dependent on the integrity of the
      motifs. We have further evaluated the effects of Ca(2+) on subunit composition,
      subcellular targeting, catalytic activity, and function during the cell cycle of
      a PR72-containing PP2A trimer (PP2A(T72)) by site-directed mutagenesis of either
      or both motifs. The results suggest that integrity of EF2 is required for A/PR65
      subunit interaction and proper nuclear targeting of PR72, whereas EF1 might
      mediate the effects of Ca(2+) on PP2A(T72) activity in vitro and is at least
      partially required for the ability of PR72 to alter cell cycle progression upon
      forced expression.

PMID- 12524439
TI  - Identification of a proline-rich Akt substrate as a 14-3-3 binding partner.
AB  - Akt (also called protein kinase B) is one of the major downstream targets of the
      phosphatidylinositol 3-kinase pathway. This protein kinase has been implicated in
      insulin signaling, stimulation of cellular growth, and inhibition of apoptosis as
      well as transformation of cells. Although a number of cellular proteins have been
      identified as putative targets of the enzyme, additional substrates may play a
      role in the varied responses elicited by this enzyme. We have used a combination
      of 14-3-3 binding and recognition by an antibody to the phosphorylation consensus
      of the enzyme to identify and isolate one of the major substrates of Akt, which
      is also a 14-3-3 binding protein. This 40-kDa protein, designated PRAS40, is a
      proline-rich Akt substrate. Demonstration that it is a substrate of Akt was
      accomplished by showing that 1) PRAS40 was phosphorylated in vitro by purified
      Akt on the same site that was phosphorylated in insulin-treated cells; 2)
      activation of an inducible Akt was alone sufficient to stimulate the
      phosphorylation of PRAS40; and 3) cells lacking Akt1 and Akt2 exhibit a
      diminished ability to phosphorylate this protein. Thus, PRAS40 is a novel
      substrate of Akt, the phosphorylation of which leads to the binding of this
      protein to 14-3-3.

PMID- 12524440
TI  - Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic
      accumulation of F-actin.
AB  - PSD-Zip45/Homer1c, which contains an enabled/VASP homology 1 (EVH1) domain and
      leucine zipper motifs, is a postsynaptic density (PSD) scaffold protein that
      interacts with metabotropic glutamate receptors and the shank family. We studied
      the molecular mechanism underlying the synaptic targeting of PSD-Zip45 in
      cultured hippocampal neurons. The EVH1 domain and the extreme C-terminal leucine
      zipper motif were molecular determinants for its synaptic targeting. The
      overexpression of the mutant of the EVH1 domain or deletion of the extreme C
      terminal leucine zipper motif markedly suppressed the synaptic localization of
      endogenous shank but not PSD-95 or GKAP. In contrast, an overexpressed GKAP
      mutant lacking shank binding activity had no effect on the synaptic localization
      of shank. Actin depolymerization by latrunculin A reduced the synaptic
      localization of PSD-Zip45, shank, and F-actin but not of PSD-95 or GKAP.
      Overexpression of PSD-Zip45 enhanced the accumulation of synaptic F-actin.
      Additionally, overexpression of PSD-Zip45 and an isoform of shank induced
      synaptic enlargement in association with the further accumulation of synaptic F
      actin. The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45
      were also critical for these events. Thus, these data suggest that the PSD-Zip45
      shank and PSD-95-GKAP complexes form different synaptic compartments, and PSD
      Zip45 alone or PSD-Zip45-shank is involved in the synaptic accumulation of F
      actin.

PMID- 12524441
TI  - Integrins modulate fast excitatory transmission at hippocampal synapses.
AB  - The present study provides the first evidence that adhesion receptors belonging
      to the integrin family modulate excitatory transmission in the adult rat brain.
      Infusion of an integrin ligand (the peptide GRGDSP) into rat hippocampal slices
      reversibly increased the slope and amplitude of excitatory postsynaptic
      potentials. This effect was not accompanied by changes in paired pulse
      facilitation, a test for perturbations to transmitter release, or affected by
      suppression of inhibitory responses, suggesting by exclusion that alterations to
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate
      receptors cause the enhanced responses. A mixture of function-blocking antibodies
      to integrin subunits alpha(3), alpha(5), and alpha(v) blocked ligand effects on
      synaptic responses. The ligand-induced increases were (i) blocked by inhibitors
      of Src tyrosine kinase, antagonists of N-methyl-d-aspartate receptors, and
      inhibitors of calcium calmodulin-dependent protein kinase II and (ii) accompanied
      by phosphorylation of both the Thr(286) site on calmodulin-dependent protein
      kinase II and the Ser(831) site on the GluR1 subunit of the AMPA receptor. N
      Methyl-d-aspartate receptor antagonists blocked the latter two phosphorylation
      events, but Src kinase inhibitors did not. These results point to the conclusion
      that synaptic integrins regulate glutamatergic transmission and suggest that they
      do this by activating two signaling pathways directed at AMPA receptors.

PMID- 12524442
TI  - Identification of the minimal phosphoacceptor site required for in vivo
      activation of interferon regulatory factor 3 in response to virus and double
      stranded RNA.
AB  - The ubiquitously expressed latent interferon regulatory factor (IRF) 3
      transcription factor is activated in response to virus infection by
      phosphorylation events that target a cluster of Ser/Thr residues,
      (382)GGASSLENTVDLHISNSHPLSLTSDQY(408) at the C-terminal end of the protein. To
      delineate the minimal phosphoacceptor sites required for IRF-3 activation,
      several point mutations were generated and tested for transactivation potential
      and cAMP-response element-binding protein-binding protein/p300 coactivator
      association. Expression of the IRF-3 S396D mutant alone was sufficient to induce
      type I IFN beta, IFNalpha1, RANTES, and the interferon-stimulated gene 561
      promoters. Using SDS-PAGE and immunoblotting with a novel phosphospecific
      antibody, we show for the first time that, in vivo, IRF-3 is phosphorylated on
      Ser(396) following Sendai virus infection, expression of viral nucleocapsid, and
      double-stranded RNA treatment. These results demonstrate that Ser(396) within the
      C-terminal Ser/Thr cluster is targeted in vivo for phosphorylation following
      virus infection and plays an essential role in IRF-3 activation. The inability of
      the phosphospecific antibody to detect Ser(396) phosphorylation in
      lipopolysaccharide-treated cells suggests that other major pathways may be
      involved in IRF-3 activation following Toll-like receptor 4 stimulation.

PMID- 12524443
TI  - Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium
      ATPase 3 in insulin-secreting beta-cells.
AB  - We have previously characterized an insulin receptor substrate 1 (IRS-1)
      overexpressing beta-cell line. These beta-cells demonstrated elevated fractional
      insulin secretion and elevated cytosolic Ca(2+) levels compared with wild-type
      and vector controls. This effect of IRS-1 may be mediated via an interaction with
      the sarco-endoplasmic reticulum calcium ATPase (SERCA). Here we demonstrate that
      IRS-1 and IRS-2 localize to an endoplasmic reticulum (ER)-enriched fraction in
      beta-cells using subcellular fractionation. We also observe co-localization of
      both IRS-1 and IRS-2 with ER marker proteins using immunofluorescent confocal
      microscopy. Furthermore, immuno-electron microscopy studies confirm that IRS-1
      and SERCA3b localize to vesicles derived from the ER. In Chinese hamster ovary-T
      (CHO-T) cells transiently transfected with SERCA3b alone or together with IRS-1,
      SERCA3b co-immunoprecipitates with IRS-1. This interaction is enhanced with
      insulin treatment. SERCA3b also co-immunoprecipitates with IRS-1 in wild-type and
      IRS-1-overexpressing beta-cell lines. Ca(2+) uptake in ER-enriched fractions
      prepared from wild-type and IRS-1-overexpressing cell lines shows no significant
      difference, indicating that the previously observed decrease in Ca(2+) uptake by
      IRS-1-overexpressing cells is not the result of a defect in SERCA. Treatment of
      wild-type beta-cells with thapsigargin, an inhibitor of SERCA, resulted in an
      increase in glucose-stimulated fractional insulin secretion similar to that
      observed in IRS-1-overexpressing cells. The colocalization of IRS proteins and
      SERCA in the ER of beta-cells increases the likelihood that these proteins can
      interact with one another. Co-immunoprecipitation of IRS-1 and SERCA in CHO-T
      cells and beta-cells confirms that these proteins do indeed interact directly.
      Pharmacological inhibition of SERCA in beta-cells results in enhanced secretion
      of insulin. Taken together, our data suggest that interaction between IRS
      proteins and SERCA is an important regulatory step in insulin secretion.

PMID- 12524444
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances N
      methyl-D-aspartate receptor function and brain-derived neurotrophic factor
      expression via RACK1.
AB  - We recently identified a novel mechanism for modulation of the phosphorylation
      state and function of the N-methyl-d-aspartate (NMDA) receptor via the
      scaffolding protein RACK1. We found that RACK1 binds both the NR2B subunit of the
      NMDA receptor and the nonreceptor protein-tyrosine kinase, Fyn. RACK1 inhibits
      Fyn phosphorylation of NR2B and decreases NMDA receptor-mediated currents in CA1
      hippocampal slices (Yaka, R., Thornton, C., Vagts, A. J., Phamluong, K., Bonci,
      A., and Ron, D. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 5710-5715). Here, we
      identified the signaling cascade by which RACK1 is released from the NMDA
      receptor complex and identified the consequences of the dissociation. We found
      that activation of the cAMP/protein kinase A pathway in hippocampal slices
      induced the release of RACK1 from NR2B and Fyn. This resulted in the induction of
      NR2B phosphorylation and the enhancement of NMDA receptor-mediated activity via
      Fyn. We identified the neuropeptide, pituitary adenylate cyclase activating
      polypeptide (PACAP(1-38)), as a ligand that induced phosphorylation of NR2B and
      enhanced NMDA receptor potentials. Finally, we found that activation of the
      cAMP/protein kinase A pathway induced the movement of RACK1 to the nuclear
      compartment in dissociated hippocampal neurons. Nuclear RACK1 in turn was found
      to regulate the expression of brain-derived neurotrophic factor induced by
      PACAP(1-38). Taken together our results suggest that activation of adenylate
      cyclase by PACAP(1-38) results in the release of RACK1 from the NMDA receptor and
      Fyn. This in turn leads to NMDA receptor phosphorylation, enhanced activity
      mediated by Fyn, and to the induction of brain-derived neurotrophic factor
      expression by RACK1.

PMID- 12524445
TI  - Dependence of purinergic P2X receptor activity on ectodomain structure.
AB  - Purinergic receptors (P2XRs) activate and desensitize in response to the binding
      of extracellular nucleotides in a receptor- and ligand-specific manner, but the
      structural bases of their ligand preferences and channel kinetics have been
      incompletely characterized. Here we tested the hypothesis that affinity of
      agonists for binding domain accounts for a ligand-specific desensitization
      pattern. We generated chimeras using receptors with variable sensitivity to ATP
      in order: P2X(4)R > P2X(2a)R = P2X(2b)R P2X(7)R. Chimeras having the ectodomain
      Ile(66)-Tyr(310) sequence of P2X(2)R and Val(61)-Phe(313) sequence of P2X(7)R in
      the backbone of P2X(4)R were expressed but were non-functioning channels. P2X(2a)
      + X(4)R and P2X(2b) + X(4)R chimeras having the Val(66)-Tyr(315) ectodomain
      sequence of P2X(4)R in the backbones of P2X(2a)R and P2X(2b)R were functional and
      exhibited increased sensitivity to ligands as compared with both parental
      receptors. These chimeras also desensitized faster than parental receptors and in
      a ligand-nonspecific manner. However, like parental P2X(2b)R and P2X(2a)R,
      chimeric P2X(2b) + X(4)R desensitized more rapidly than P2X(2a) + X(4)R, and the
      rate of desensitization of P2X(2a)+X(4)R increased by substituting its Arg(371)
      Pro(376) intracellular C-terminal sequence with the Glu(376)-Gly(381) sequence of
      P2X(4)R. These results indicate the relevance of interaction between the
      ectodomain and flanking regions around the transmembrane domains on ligand
      potency and receptor activation. Furthermore, the ligand potency positively
      correlates with the rate of receptor desensitization but does not affect the C
      terminal-specific pattern of desensitization.

PMID- 12524447
TI  - The JNK-interacting protein-1 scaffold protein targets MAPK phosphatase-7 to
      dephosphorylate JNK.
AB  - The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases
      (MAPKs) are activated by pleiotropic signals including environmental stresses,
      growth factors, and hormones. A subset of JNK can bind to distinct scaffold
      proteins that also bind upstream kinases of the JNK pathway, allowing sequential
      kinase activation within a signaling module. The JNK-interacting protein-1 (JIP
      1) scaffold protein specifically binds JNK, MAP kinase kinase 7, and members of
      the MLK family and is essential for stress-mediated JNK activation in neurones.
      Here we report that JIP-1 also binds the dual-specificity phosphatases MKP7 and
      M3/6 via a region independent of its JNK binding domain. The C-terminal region of
      MKP7, homologous to that of M3/6 but not other DSPs, is required for interaction
      with JIP-1. When MKP7 is bound to JIP-1 it reduces JNK activation leading to
      reduced phosphorylation of the JNK target c-Jun. These results indicate that the
      JIP-1 scaffold protein modulates JNK signaling via association with both protein
      kinases and protein phosphatases that target JNK.

PMID- 12524446
TI  - Endogenous RGS protein action modulates mu-opioid signaling through Galphao.
      Effects on adenylyl cyclase, extracellular signal-regulated kinases, and
      intracellular calcium pathways.
AB  - RGS (regulators of G protein signaling) proteins are GTPase-activating proteins
      for the Galpha subunits of heterotrimeric G proteins and act to regulate
      signaling by rapidly cycling G protein. RGS proteins may integrate receptors and
      signaling pathways by physical or kinetic scaffolding mechanisms. To determine
      whether this results in enhancement and/or selectivity of agonist signaling, we
      have prepared C6 cells stably expressing the mu-opioid receptor and either
      pertussis toxin-insensitive or RGS- and pertussis toxin-insensitive Galpha(o). We
      have compared the activation of G protein, inhibition of adenylyl cyclase,
      stimulation of intracellular calcium release, and activation of the ERK1/2 MAPK
      pathway between cells expressing mutant Galpha(o) that is either RGS-insensitive
      or RGS-sensitive. The mu-receptor agonist [d-Ala(2),MePhe(4),Gly(5)-ol]enkephalin
      and partial agonist morphine were much more potent and/or had an increased
      maximal effect in inhibiting adenylyl cyclase and in activating MAPK in cells
      expressing RGS-insensitive Galpha(o). In contrast, mu-opioid agonist increases in
      intracellular calcium were less affected. The results are consistent with the
      hypothesis that the GTPase-activating protein activity of RGS proteins provides a
      control that limits agonist action through effector pathways and may contribute
      to selectivity of activation of intracellular signaling pathways.

PMID- 12524448
TI  - Homodimerization of neuropeptide y receptors investigated by fluorescence
      resonance energy transfer in living cells.
AB  - Up to now neuropeptide Y (NPY) receptors, which belong to the large family of G
      protein-coupled receptors and are involved in a broad range of physiological
      processes, are believed to act as monomers. Studies with the Y(1)-receptor
      antagonist and Y(4)-receptor agonist GR231118, which binds with a 250-fold higher
      affinity than its monomer, led to the first speculation that NPY receptors can
      form homodimers. In the present work we used the fluorescence resonance energy
      transfer (FRET) to study homodimerization of the hY(1)-, hY(2)-, and hY(5)
      receptors in living cells. For this purpose, we generated fusion proteins of NPY
      receptors and green fluorescent protein or spectral variants of green fluorescent
      protein (cyan, yellow, and red fluorescent protein), which can be used as FRET
      pairs. Two different FRET techniques, fluorescence microscopy and fluorescence
      spectroscopy, were applied. Both techniques clearly showed that the hY(1)-, hY(2)
      , and hY(5)-NPY receptor subtypes are able to form homodimers. By using
      transiently transfected cells, as well as a stable cell line expressing the hY(2)
      GFP fusion protein, we could demonstrate that the Y-GFP fusion proteins are still
      functional and that dimerization varies from 26 to 44% dependent on the receptor.
      However, homodimerization is influenced neither by NPY nor by Galpha protein
      binding.

PMID- 12524449
TI  - Protein interactions within the N-end rule ubiquitin ligation pathway.
AB  - Rate studies have been employed as a reporter function to probe protein-protein
      interactions within a biochemically defined reconstituted N-end rule ubiquitin
      ligation pathway. The concentration dependence for E1-catalyzed HsUbc2b/E2(14kb)
      transthiolation is hyperbolic and yields K(m) values of 102 +/- 13 nm and 123 +/-
      19 nm for high affinity binding to rabbit and human E1/Uba1 orthologs.
      Competitive inhibition by the inactive substrate and product analogs HsUbc2bC88A
      (K(i) = 104 +/- 15 nm) and HsUbc2bC88S-ubiquitin oxyester (K(i) = 169 +/- 17 nm),
      respectively, indicates that the ubiquitin moiety contributes little to E1
      binding. Under conditions of rate-limiting E3alpha-catalyzed conjugation to human
      alpha-lactalbumin, HsUbc2b-ubiquitin thiolester exhibits a K(i) of 54 +/- 18 nm
      and is competitively inhibited by the substrate analog HsUbc2bC88S-ubiquitin
      oxyester (K(i) = 66 +/- 29 nm). In contrast, the ligase product analog
      HsUbc2bC88A exhibits a K(i) of 440 +/- 55 nm with respect to the wild type
      HsUbc2b-ubiquitin thiolester, demonstrating that ubiquitin binding contributes to
      the ability of E3alpha to discriminate between substrate and product E2. A survey
      of E1 and E2 isoform distribution in selected cell lines demonstrates that Ubc2
      isoforms are the predominant intracellular ubiquitin carrier protein.
      Intracellular levels of E1 and Ubc2 are micromolar and approximately equal based
      on in vitro quantitation by stoichiometric (125)I-ubiquitin thiolester formation.
      Comparison of intracellular E1 and Ubc2 pools with the corresponding ubiquitin
      pools reveals that most of the free ubiquitin in cells is present as thiolesters
      to the components of the conjugation pathways. The present data represent the
      first comprehensive analysis of protein interactions within a ubiquitin ligation
      pathway.

PMID- 12524450
TI  - Benzo[a]pyrene-dG adduct interference illuminates the interface of vaccinia
      topoisomerase with the DNA minor groove.
AB  - Vaccinia DNA topoisomerase forms a covalent DNA-(3'-phosphotyrosyl)-enzyme
      intermediate at a pentapyrimidine target site 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p
      downward arrow in duplex DNA. The enzyme engages the target site within a C
      shaped protein clamp. Here we mapped the interface of topoisomerase with the DNA
      minor groove by introducing chiral C-10 R and S 7,8-diol 9,10-epoxide adducts of
      benzo[a]pyrene (BP) at single N(2)-deoxyguanosine (dG) positions within the
      nonscissile DNA strand. These trans opened BPdG adducts fit into the minor groove
      without perturbing helix conformation or base pairing, and the R and S
      diastereomers are oriented in opposite directions within the minor groove. We
      measured the effects of the BPdG adducts on the rate and extent of single
      turnover DNA transesterification. We observed a sharp margin of interference
      effects, whereby +5 and -2 BPdG modifications were well tolerated but +4, +3, and
      -1 BPdG adducts were severely deleterious. Stereoselective effects at the -1
      nucleoside (the R isomer interfered, whereas the S isomer did not) delineated at
      high resolution the downstream border of the minor groove interface. BPdG
      inhibition of transesterification is likely caused by steric exclusion of
      constituents of the topoisomerase from the minor groove. We also applied the BPdG
      interference method to probe the interactions of exonuclease III with the minor
      groove. DNAs containing these BPdG adducts were protected from digestion by
      exonuclease III, which was consistently arrested at positions 2-4 nucleotides
      prior to the BP-modified guanosine.

PMID- 12524451
TI  - Lysophosphatidic acid promotes survival and differentiation of rat Schwann cells.
AB  - Lysophosphatidic acid (LPA; 1-acyl-sn-glycerol-3-phosphate), an abundant
      constituent of serum, mediates multiple biological responses via G protein
      coupled serpentine receptors. Schwann cells express the LPA receptors (Edg
      receptors), which, once activated, have the potential to signal through G(alphai)
      to activate p21(ras) and phosphatidylinositol 3-kinase, through G(alphaq) to
      activate phospholipase C, or through G(q12/13) to activate the Rho pathway. We
      found that the addition of serum or LPA to serum-starved Schwann cells rapidly
      (10 min) induced the appearance of actin stress fibers via a Rho-mediated
      pathway. Furthermore, LPA was able to rescue Schwann cells from apoptosis in a
      G(alphai)/phosphatidylinositol 3-kinase/MEK/MAPK-dependent manner. In addition,
      LPA increased the expression of myelin protein P(0) in Schwann cells in a
      Galpha(i)-independent manner but dependent on protein kinase C. By means of
      pharmacological and overexpression approaches, we found that the novel isozyme
      protein kinase Cdelta was required for myelin P(0) expression. Thus, the multiple
      effects of LPA in Schwann cells (actin reorganization, survival, and myelin gene
      expression) appear to be mediated through the different G protein-dependent
      pathways activated by the LPA receptor.

PMID- 12524452
TI  - Involvement of CjMDR1, a plant multidrug-resistance-type ATP-binding cassette
      protein, in alkaloid transport in Coptis japonica.
AB  - Alkaloids comprise one of the largest groups of plant secondary metabolites.
      Berberine, a benzylisoquinoline alkaloid, is preferentially accumulated in the
      rhizome of Coptis japonica, a ranunculaceous plant, whereas gene expression for
      berberine biosynthetic enzymes has been observed specifically in root tissues,
      which suggests that berberine synthesized in the root is transported to the
      rhizome, where there is high accumulation. We recently isolated a cDNA encoding a
      multidrug-resistance protein (MDR)-type ATP-binding cassette (ABC) transporter
      (Cjmdr1) from berberine-producing cultured C. japonica cells, which is highly
      expressed in the rhizome. Functional analysis of Cjmdr1 by using a Xenopus oocyte
      expression system showed that CjMDR1 transported berberine in an inward
      direction, resulting in a higher accumulation of berberine in Cjmdr1-injected
      oocytes than in the control. Typical inhibitors of ABC proteins, such as
      vanadate, nifedipine, and glibenclamide, as well as ATP depletion, clearly
      inhibited this CjMDR1-dependent berberine uptake, suggesting that CjMDR1
      functioned as an ABC transporter. Conventional membrane separation methods showed
      that CjMDR1 was localized in the plasma membrane of C. japonica cells. In situ
      hybridization indicated that Cjmdr1 mRNA was expressed preferentially in xylem
      tissues of the rhizome. These findings strongly suggest that CjMDR1 is involved
      in the translocation of berberine from the root to the rhizome.

PMID- 12524453
TI  - Directed evolution approach to a structural genomics project: Rv2002 from
      Mycobacterium tuberculosis.
AB  - One of the serious bottlenecks in structural genomics projects is overexpression
      of the target proteins in soluble form. We have applied the directed evolution
      technique and prepared soluble mutants of the Mycobacterium tuberculosis Rv2002
      gene product, the wild type of which had been expressed as inclusion bodies in
      Escherichia coli. A triple mutant I6TV47MT69K (Rv2002-M3) was chosen for
      structural and functional characterizations. Enzymatic assays indicate that the
      Rv2002-M3 protein has a high catalytic activity as a NADH-dependent 3alpha,
      20beta-hydroxysteroid dehydrogenase. We have determined the crystal structures of
      a binary complex with NAD(+) and a ternary complex with androsterone and NADH.
      The structure reveals that Asp-38 determines the cofactor specificity. The
      catalytic site includes the triad Ser-140Tyr-153Lys-157. Additionally, it has an
      unusual feature, Glu-142. Enzymatic assays of the E142A mutant of Rv2002-M3
      indicate that Glu-142 reverses the effect of Lys-157 in influencing the pKa of
      Tyr-153. This study suggests that the Rv2002 gene product is a unique member of
      the SDR family and is likely to be involved in steroid metabolism in M.
      tuberculosis. Our work demonstrates the power of the directed evolution technique
      as a general way of overcoming the difficulties in overexpressing the target
      proteins in soluble form.

PMID- 12524454
TI  - Routes to S-nitroso-hemoglobin formation with heme redox and preferential
      reactivity in the beta subunits.
AB  - Previous studies of the interactions of NO with human hemoglobin have implied the
      predominance of reaction channels that alternatively eliminate NO by converting
      it to nitrate, or tightly complex it on the alpha subunit ferrous hemes. Both
      channels could effectively quench NO bioactivity. More recent work has raised the
      idea that NO groups can efficiently transfer from the hemes to cysteine thiols
      within the beta subunit (cysbeta-93) to form bioactive nitrosothiols. The
      regulation of NO function, through its chemical position in the hemoglobin, is
      supported by response to oxygen and to redox agents that modulate the molecular
      and electronic structure of the protein. In this article, we focus on reactions
      in which Fe(III) hemes could provide the oxidative requirements of this NO-group
      transfer chemistry. We report a detailed investigation of the reductive
      nitrosylation of human met-Hb, in which we demonstrate the production of S
      nitroso (SNO)-Hb through a heme-Fe(III)NO intermediate. The production of SNO-Hb
      is strongly favored (over nitrite) when NO is gradually introduced in limited
      total quantities; in this situation, moreover, heme nitrosylation occurs
      primarily within the beta subunits of the hemoglobin tetramer. SNO-Hb can
      similarly be produced when Fe(II)NO hemes are subjected to mild oxidation. The
      reaction of deoxygenated hemoglobin with limited quantities of nitrite leads to
      the production of beta subunit Fe(II)NO hemes, with SNO-Hb produced on subsequent
      oxygenation. The common theme of these reactions is the effective coupling of
      heme-iron and NO redox chemistries. Collectively, they establish a connectivity
      between hemes and thiols in Hb, through which NO is readily dislodged from
      storage on the heme to form bioactive SNO-Hb.

PMID- 12524455
TI  - Correlated terrestrial and marine evidence for global climate changes before mass
      extinction at the Cretaceous-Paleogene boundary.
AB  - Terrestrial climates near the time of the end-Cretaceous mass extinction are
      poorly known, limiting understanding of environmentally driven changes in
      biodiversity that occurred before bolide impact. We estimate paleotemperatures
      for the last approximately 1.1 million years of the Cretaceous ( approximately
      66.6-65.5 million years ago, Ma) by using fossil plants from North Dakota and
      employ paleomagnetic stratigraphy to correlate the results to foraminiferal
      paleoclimatic data from four middle- and high-latitude sites. Both plants and
      foraminifera indicate warming near 66.0 Ma, a warming peak from approximately
      65.8 to 65.6 Ma, and cooling near 65.6 Ma, suggesting that these were global
      climate shifts. The warming peak coincides with the immigration of a thermophilic
      flora, maximum plant diversity, and the poleward range expansion of thermophilic
      foraminifera. Plant data indicate the continuation of relatively cool
      temperatures across the Cretaceous-Paleogene boundary; there is no indication of
      a major warming immediately after the boundary as previously reported. Our
      temperature proxies correspond well with recent pCO(2) data from paleosol
      carbonate, suggesting a coupling of pCO(2) and temperature. To the extent that
      biodiversity is correlated with temperature, estimates of the severity of end
      Cretaceous extinctions that are based on occurrence data from the warming peak
      are probably inflated, as we illustrate for North Dakota plants. However, our
      analysis of climate and facies considerations shows that the effects of bolide
      impact should be regarded as the most significant contributor to these plant
      extinctions.

PMID- 12524456
TI  - A novel plant protein undergoing light-induced phosphorylation and release from
      the photosynthetic thylakoid membranes.
AB  - The characteristics of a phosphoprotein with a relative electrophoretic mobility
      of 12 kDa have been unknown during two decades of studies on redox-dependent
      protein phosphorylation in plant photosynthetic membranes. Digestion of this
      protein from spinach thylakoid membranes with trypsin and subsequent tandem
      nanospray-quadrupole-time-of-flight mass spectrometry of the peptides revealed a
      protein sequence that did not correspond to any previously known protein.
      Sequencing of the corresponding cDNA uncovered a gene for a precursor protein
      with a transit peptide followed by a strongly basic mature protein with a
      molecular mass of 8,640 Da. Genes encoding homologous proteins were found on
      chromosome 3 of Arabidopsis and rice as well as in ESTs from 20 different plant
      species, but not from any other organisms. The protein can be released from the
      membrane with high salt and is also partially released in response to light
      induced phosphorylation of thylakoids, in contrast to all other known thylakoid
      phosphoproteins, which are integral to the membrane. On the basis of its
      properties, this plant-specific protein is named thylakoid soluble phosphoprotein
      of 9 kDa (TSP9). Mass spectrometric analyses revealed the existence of non-, mono
      , di-, and triphosphorylated forms of TSP9 and phosphorylation of three distinct
      threonine residues in the central part of the protein. The phosphorylation and
      release of TSP9 from the photosynthetic membrane on illumination favor
      participation of this basic protein in cell signaling and regulation of plant
      gene expression in response to changing light conditions.

PMID- 12524457
TI  - CTCF functions as a critical regulator of cell-cycle arrest and death after
      ligation of the B cell receptor on immature B cells.
AB  - The WEHI 231 B cell lymphoma is used as a model of self-tolerance by clonal
      deletion because B cell receptor (BCR) ligation results in apoptosis. Two
      critical events precede cell death: an early rise and fall in expression of MYC
      and cell-cycle arrest associated with enhanced expression of p21, p27, and p53.
      CTCF is a transcription factor identified as a repressor of MYC recently shown to
      cause cell growth inhibition. The present studies demonstrate that BCR ligation
      of WEHI 231 as well as of normal immature B cells greatly increased expression of
      CTCF in association with down-regulation of MYC followed by growth arrest and
      cell death. Conditional expression of CTCF in WEHI 231 mimicked BCR ligation with
      activated cells showing repressed expression of MYC, enhanced expression of p27,
      p21, p53, and p19(ARF), and inhibition of cell growth and induction of apoptosis.
      In keeping with a central role for CTCF in control of B cell death, conditional
      expression of a CTCF antisense construct in WEHI 231 resulted in inhibition of
      p27, p21, p53, and p19(ARF) in association with enhanced expression of MYC.
      Activation of the endogenous CTCF locus by BCR ligation was also mimicked by
      three other routes to apoptotic death in WEHI 231: inhibition of the
      phosphoinositide 3-kinase or mTORFRAP signaling cascades and treatment with
      transforming growth factor (TGF)-beta. Rapid activation of CTCF by BCR ligation
      or treatment with TGF-beta was suppressed by ligation of CD40. These results
      demonstrate that CTCF is a common determinant to different pathways of death
      signaling in immature B cells.

PMID- 12524458
TI  - Macula densa cell signaling.
AB  - Macula densa cells are renal sensor elements that detect changes in distal
      tubular fluid composition and transmit signals to the glomerular vascular
      elements. This tubuloglomerular feedback mechanism plays an important role in
      regulating glomerular filtration rate and blood flow. Macula densa cells detect
      changes in luminal sodium chloride concentration through a complex series of ion
      transport-related intracellular events. NaCl entry via a Na:K:2Cl cotransporter
      and Cl exit through a basolateral channel lead to cell depolarization and
      increases in cytosolic calcium. Na/H exchange (NHE2) results in cell
      alkalization, whereas intracellular [Na] is regulated by an apically located
      H(Na)-K ATPase and not by the traditional basolateral Na:K ATPase. Communication
      from macula densa cells to the glomerular vascular elements involves ATP release
      across the macula densa basolateral membrane through a maxi-anion channel. The
      adaptation of multi-photon microscopy is providing new insights into macula densa
      glomerular signaling.

PMID- 12524459
TI  - In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics:
      implications for brain function.
AB  - Until very recently, non-invasive measurement of the glutamate-glutamine cycle in
      the intact mammalian brain had not been possible. In this review, we describe
      some studies that have led to quantitative assessment of the glutamate-glutamine
      cycle (Vcyc), as well as other important metabolic fluxes (e.g., glucose
      oxidation, CMRglc(ox)), with (13)C magnetic resonance spectroscopy (MRS) in vivo.
      These (13)C MRS studies clearly demonstrate that glutamate released from
      presynaptic neurons is taken up by the astrocyte for subsequent glutamine
      synthesis. Contrary to the earlier concept of a small, metabolically inactive
      neurotransmitter pool, in vivo (13)C MRS studies demonstrate that glutamate
      release and recycling is a major metabolic pathway that cannot be distinguished
      from its actions of neurotransmission. Furthermore, the in vivo (13)C MRS studies
      demonstrate in the rat cerebral cortex that increases in Vcyc and neuronal
      CMRglc(ox) are linearly related with a close to 1:1 slope. Measurements in human
      cerebral cortex are in agreement with this result. This relationship is
      consistent with more than two thirds of the energy yielded by glucose oxidation
      being used to support events associated with glutamate neurotransmission, and it
      supports a molecular model of a stoichiometric coupling between glutamate
      neurotransmission and functional glucose oxidation. (13)C MRS measurements of
      resting human cerebral cortex have found a high level of glutamate-glutamine
      cycling. This high resting neuronal activity, which is subtracted away in brain
      mapping studies by positron emission tomography (PET) and functional magnetic
      resonance imaging (fMRI), has significant implications for the interpretations of
      functional imaging data. Here we review and discuss the importance of
      neurotransmission and neuroenergetics as measured by (13)C MRS for understanding
      brain function and interpreting fMRI.

PMID- 12524460
TI  - Cardiac hypertrophy: the good, the bad, and the ugly.
AB  - Cardiac hypertrophy is the heart's response to a variety of extrinsic and
      intrinsic stimuli that impose increased biomechanical stress. While hypertrophy
      can eventually normalize wall tension, it is associated with an unfavorable
      outcome and threatens affected patients with sudden death or progression to overt
      heart failure. Accumulating evidence from studies in human patients and animal
      models suggests that in most instances hypertrophy is not a compensatory response
      to the change in mechanical load, but rather is a maladaptive process.
      Accordingly, modulation of myocardial growth without adversely affecting
      contractile function is increasingly recognized as a potentially auspicious
      approach in the prevention and treatment of heart failure. In this review, we
      summarize recent insights into hypertrophic signaling and consider several novel
      antihypertrophic strategies.

PMID- 12524463
TI  - Mammalian urea transporters.
AB  - Urea plays a key role in the urine-concentrating mechanism. Physiologic and
      molecular data demonstrate that urea transport in kidney and red blood cells
      occurs by specific urea transporter proteins. Two gene families for facilitated
      urea transporters, UT-A and UT-B, and several urea transporter cDNA isoforms have
      been cloned from human, rat, mouse, and several non-mammalian species. Polyclonal
      antibodies have been generated to many of the urea transporter proteins, and
      several novel findings have resulted from their use in integrative animal
      studies. For example, (a) vasopressin increases the phosphorylation of UT-A1 in
      rat inner medullary collecting duct; (b) UT-A1 protein abundance is increased in
      the rat inner medulla during conditions in which urine-concentrating ability is
      reduced; and (c) urea transporters are expressed in non-renal tissues, and UT-A
      protein abundance is up-regulated in uremia in both liver and heart. In addition
      to the facilitated urea transporters, functional evidence exists for active urea
      transport in the kidney collecting duct. This review summarizes the physiologic
      evidence for the existence of facilitated and active urea transporters, the
      molecular biology of the facilitated urea transporter gene families and cDNAs,
      and integrative studies into urea transporter protein regulation, both in the
      kidney and in other organs.

PMID- 12524462
TI  - Structure and mechanism of Na,K-ATPase: functional sites and their interactions.
AB  - The cell membrane Na,K-ATPase is a member of the P-type family of active cation
      transport proteins. Recently the molecular structure of the related sarcoplasmic
      reticulum Ca-ATPase in an E1 conformation has been determined at 2.6 A
      resolution. Furthermore, theoretical models of the Ca-ATPase in E2 conformations
      are available. As a result of these developments, these structural data have
      allowed construction of homology models that address the central questions of
      mechanism of active cation transport by all P-type cation pumps. This review
      relates recent evidence on functional sites of Na,K-ATPase for the substrate
      (ATP), the essential cofactor (Mg(2+) ions), and the transported cations (Na(+)
      and K(+)) to the molecular structure. The essential elements of the Ca-ATPase
      structure, including 10 transmembrane helices and well-defined N, P, and A
      cytoplasmic domains, are common to all PII-type pumps such as Na,K-ATPase and H,K
      ATPases. However, for Na,K-ATPase and H,K-ATPase, which consist of both alpha-
      and beta-subunits, there may be some detailed differences in regions of subunit
      interactions. Mutagenesis, proteolytic cleavage, and transition metal-catalyzed
      oxidative cleavages are providing much evidence about residues involved in
      binding of Na(+), K(+), ATP, and Mg(2+) ions and changes accompanying E1-E2 or E1
      P-E2-P conformational transitions. We discuss this evidence in relation to N, P,
      and A cytoplasmic domain interactions, and long-range interactions between the
      active site and the Na(+) and K(+) sites in the transmembrane segments, for the
      different steps of the catalytic cycle.

PMID- 12524461
TI  - Current status of gene therapy for inherited lung diseases.
AB  - Gene therapy as a treatment modality for pulmonary disorders has attracted
      significant interest over the past decade. Since the initiation of the first
      clinical trials for cystic fibrosis lung disease using recombinant adenovirus in
      the early 1990s, the field has encountered numerous obstacles including vector
      inflammation, inefficient delivery, and vector production. Despite these
      obstacles, enthusiasm for lung gene therapy remains high. In part, this
      enthusiasm is fueled through the diligence of numerous researchers whose studies
      continue to reveal great potential of new gene transfer vectors that demonstrate
      increased tropism for airway epithelia. Several newly identified serotypes of
      adeno-associated virus have demonstrated substantial promise in animal models and
      will likely surface soon in clinical trials. Furthermore, an increased
      understanding of vector biology has also led to the development of new
      technologies to enhance the efficiency and selectivity of gene delivery to the
      lung. Although the promise of gene therapy to the lung has yet to be realized,
      the recent concentrated efforts in the field that focus on the basic virology of
      vector development will undoubtedly reap great rewards over the next decade in
      treating lung diseases.

PMID- 12524464
TI  - Transducing touch in Caenorhabditis elegans.
AB  - Mechanosensation has been studied for decades, but understanding of its molecular
      mechanism is only now emerging from studies in Caenorhabditis elegans and
      Drosophila melanogaster. In both cases, the entry point proved to be genetic
      screens that allowed molecules needed for mechanosensation to be identified
      without any prior understanding of the likely components. In C. elegans, genetic
      screens revealed molecules needed for touch sensation along the body wall and
      other regions of force sensitivity. Members of two extensive membrane protein
      families have emerged as candidate sensory mechanotransduction channels: mec-4
      and mec-10, which encode amiloride-sensitive channels (ASCs or DEG/ENaCs), and
      osm-9, which encodes a TRP ion channel. There are roughly 50 other members of
      these families whose functions in C. elegans are unknown. This article classifies
      these channels in C. elegans, with an emphasis on insights into their function
      derived from mutation. We also review the neuronal cell types in which these
      channels might be expressed and mediate mechanotransduction.

PMID- 12524465
TI  - Origins and consequences of mitochondrial variation in vertebrate muscle.
AB  - This review addresses the mechanisms by which mitochondrial structure and
      function are regulated, with a focus on vertebrate muscle. We consider the
      adaptive remodeling that arises during physiological transitions such as
      differentiation, development, and contractile activity. Parallels are drawn
      between such phenotypic changes and the pattern of change arising over
      evolutionary time, as suggested by interspecies comparisons. We address the
      physiological and evolutionary relationships between ATP production,
      thermogenesis, and superoxide generation in the context of mitochondrial
      function. Our discussion of mitochondrial structure focuses on the regulation of
      membrane composition and maintenance of the three-dimensional reticulum. Current
      studies of mitochondrial biogenesis strive to integrate muscle functional
      parameters with signal transduction and molecular genetics, providing insight
      into the origins of variation arising between physiological states, fiber types,
      and species.

PMID- 12524466
TI  - What's behind the health expenditure trends?
AB  - In this paper, we review the literature on a number of the potential explanations
      for the rise in health care expenditures in the United States: the aging
      population, the costs of dying, technology, physician incomes, administrative
      costs, prescription drugs, managed care, and the underfunding of public health.
      Our goal is not to pass definitive judgment on the force(s) driving health care
      costs, but rather to make the reader a more educated consumer of these widely
      cited data. We place special emphasis on how health expenditures are measured and
      the inherent weaknesses in the methodology. We find that frequently it is
      difficult to accurately estimate how individual forces influence total health
      care expenditures. Moreover, we conclude that interpreting the causes of the rise
      in expenditures goes beyond simple observations of trends and depends on how we
      value various segments and aspects of health and health care.

PMID- 12524467
TI  - Erythropoietin: physiology and pharmacology update.
AB  - This minireview is an update of a 1997 review on erythropoietin (EPO) in this
      journal. EPO is a 30,400-dalton glycoprotein that regulates red cell production.
      In the human, EPO is produced by peritubular cells in the kidneys of the adult
      and in hepatocytes in the fetus. Small amounts of extra-renal EPO are produced by
      the liver in adult human subjects. EPO binds to an erythroid progenitor cell
      surface receptor that includes a p66 chain, and, when activated, the p66 protein
      becomes dimerized. EPO receptor activation induces a JAK2 tyrosine kinase, which
      leads to tyrosine phosphorylation of the EPO receptor and several proteins. EPO
      receptor binding leads to intracellular activation of the Ras/mitogen-activated
      kinase pathway, which is involved with cell proliferation, phosphatidylinositol 3
      kinase, and STATS 1, 3, 5A, and 5B transcriptional factors. EPO acts primarily to
      rescue erythroid cells from apoptosis (programmed cell death) to increase their
      survival. EPO acts synergistically with several growth factors (SCF, GM-CSF, 1L
      3, and IGF-1) to cause maturation and proliferation of erythroid progenitor cells
      (primarily colony-forming unit-E). Oxygen-dependent regulation of EPO gene
      expression is postulated to be controlled by a hypoxia-inducible transcription
      factor (HIF-1alpha). Hypoxia-inducible EPO production is controlled by a 50-bp
      hypoxia-inducible enhancer that is approximately 120 bp 3' to the polyadenylation
      site. Hypoxia signal transduction pathways involve kinases A and C, phospholipase
      A(2), and transcription factors ATF-1 and CREB-1. A model has been proposed for
      adenosine activation of EPO production that involves protein kinases A and C and
      the phospholipase A(2) pathway. Other effects of EPO include a hematocrit
      independent, vasoconstriction-dependent hypertension, increased endothelin
      production, upregulation of tissue renin, change in vascular tissue
      prostaglandins production, stimulation of angiogenesis, and stimulation of
      endothelial and vascular smooth muscle cell proliferation. Recombinant human EPO
      (rHuEPO) is currently being used to treat patients with anemias associated with
      chronic renal failure, AIDS patients with anemia due to treatment with
      zidovudine, nonmyeloid malignancies in patients treated with chemotherapeutic
      agents, perioperative surgical patients, and autologous blood donation. A novel
      erythropoiesis-stimulating factor (NESP, darbepoetin) has been synthesized and
      when compared with rHuEPO, NESP has a higher carbohydrate content (52% vs 40%), a
      longer plasma half-life, the amino acid sequence differs from that of native
      human EPO at five positions, and has been reported to maintain hemoglobin levels
      just as effectively in patients with chronic renal failure as rHuEPO at less
      frequent dosing. The use of rHuEPO and darbepoetin to enhance athletic
      performance is officially banned by most sports-governing bodies because the
      excessive erythrocytosis can lead to increased thrombogenicity and can cause deep
      vein, coronary, and cerebral thromboses.

PMID- 12524468
TI  - Neonatal nutrition: metabolic programming of pancreatic islets and obesity.
AB  - Obese individuals are more likely to suffer from diseases termed the "metabolic
      syndrome," which includes type 2 diabetes. It is now recognized that early life
      dietary experiences play an important role in the etiology of such diseases. In
      this context, the consequences of a high carbohydrate (HC) dietary intervention
      in neonatal rats is being studied in our laboratory. Artificial rearing of 4-day
      old rat pups on a HC milk formula up to Day 24 results in the immediate onset of
      hyperinsulinemia, which persists throughout the period of dietary intervention.
      Several adaptations at the biochemical, cellular, and molecular levels in the
      islets of these HC rats support the onset and persistence of the hyperinsulinemic
      condition during this period. Some of these adaptations include a distinct
      leftward shift in the insulin secretory capacity, increased hexokinase activity,
      increased gene expression of preproinsulin and related transcription factors and
      specific kinases in 12-day-old HC islets, and alterations in the number and size
      of islets. These adaptations are programmed and expressed in adulthood thereby
      sustain the hyperinsulinemic condition in the postweaning period and form the
      basis for adult-onset obesity. HC females spontaneously transmit the HC phenotype
      (chronic hyperinsulinemia and adult-onset obesity) to their progeny.
      Collectively, our results indicate that even a mere switch in the nature of the
      source of calories (from fat rich in rat milk to carbohydrate rich in the HC milk
      formula) during critical phases of early development in the rat results in
      metabolic programming of islet functions leading to chronic hyperinsulinemia
      (throughout life) and adult-onset obesity. This metabolic programming, once
      established, forms a vicious cycle because HC female rats spontaneously transmit
      the HC phenotype to their progeny. The results from our laboratory in the context
      of metabolic programming due to neonatal nutritional experiences are discussed in
      this review.

PMID- 12524469
TI  - Leptin-induced changes in body composition in high fat-fed mice.
AB  - Female C57BL/6J mice were adapted to 10% or 45% kcal fat diets for 8 weeks.
      Continuous intraperitoneal infusion of 10 micro g of leptin/day from a
      miniosmotic pump transiently inhibited food intake in low fat-fed but not high
      fat-fed mice. In contrast, both low and high fat-fed leptin-infused mice were
      less fat than their phosphate-buffered saline (PBS) controls after 13 days.
      Leptin infusion inhibited insulin release but did not change glucose clearance in
      low fat-fed mice during a glucose tolerance test. A single intraperitoneal
      injection of 30 micro g of leptin inhibited 24-hr energy intake and inhibited
      weight gain in both low and high fat-fed mice. Insulin responsiveness was
      improved in high fat-fed mice during an insulin sensitivity test due to an
      exaggerated elevation of circulating insulin concentrations. Thus, leptin
      infusion reduced adiposity independently of energy intake in high fat-fed mice
      and improved insulin sensitivity in low fat-fed mice, whereas leptin injections,
      which produced much greater, but transient, increases in serum leptin
      concentration, inhibited energy intake in both low and high fat-fed mice.

PMID- 12524470
TI  - Abnormal relaxin secretion during pregnancy in women with type 1 diabetes.
AB  - To test the hypothesis that relaxin may play a role in the fetal abnormalities
      associated with pregnancy in type 1 diabetic women, we previously compared
      gestational relaxin concentrations in diabetic and clinically normal women using
      a porcine relaxin radioimmunoassay (RIA): Serum immunoactive relaxin was
      significantly (P < 0.001) elevated in the diabetic women. To confirm and extend
      this work in a larger group of subjects, we have now used an enzyme-linked
      immunosorbent assay (ELISA) specific for human H2 relaxin (the normal human gene
      product) to determine immunoactive serum relaxin concentrations in serial samples
      from 61 Type 1 diabetic and 21 normal pregnant women. Samples from 22 of the
      diabetic and nine of the normal women were also directly compared in the porcine
      relaxin RIA. ELISA-determined serum relaxin was higher (P < 0.001) at 24 and 36
      weeks of pregnancy in type 1 diabetic women than in controls, confirming previous
      findings. However, the geometric mean increase in immunoactive relaxin
      concentration in identical samples from pregnant diabetic women over that of
      controls was significantly greater with the RIA than with the ELISA (271% vs 44%;
      P < 0.001). To investigate this discrepancy, the specificity and epitope
      selectivity of the RIA and the ELISA were compared using several synthetic
      polypeptides, including human relaxins H1 and H2, and relaxin and insulin
      derivatives. Both assays showed great specificity, but the porcine RIA
      selectively identified the epitopes of the receptor-binding domain of the relaxin
      B chain and cross-reacted strongly with H1 and H2 relaxins. In contrast, only the
      H2 peptide was detected by the ELISA antiserum. Therefore, the marked discrepancy
      between the RIA and the ELISA could be due to the presence in the diabetic
      samples of another relaxin-like molecule in addition to the normal H2 relaxin.
      The biological consequences of elevated serum relaxin in diabetic pregnancy
      remain to be elucidated.

PMID- 12524471
TI  - Prolonged prenatal hypernatremia alters neuroendocrine and electrolyte
      homeostasis in neonatal sheep.
AB  - Arginine vasopressin (AVP) is a neuroendocrine hormone synthesized in the
      hypothalamus, and is stored and secreted by the posterior pituitary gland in
      response to stimuli such as plasma hypertonicity and hypotension. The primary
      physiologic roles of AVP include plasma osmolality and blood pressure regulation.
      We have previously demonstrated that chronic prenatal plasma hypertonicity alters
      the AVP regulatory pathway in newborn lambs. The objectives of the present study
      were to evaluate prolonged effects of antenatal plasma hypertonicity on neonatal
      plasma osmoregulation. Pregnant ewes at 119 +/- 3 days of gestation were water
      restricted to achieve and maintain hypertonicity until normal-term delivery.
      After delivery, ewes were provided food and water ad libitum and lambs were
      allowed maternal nursing. At the age of 28 days, blood samples were obtained for
      the analysis of plasma osmolality, electrolytes, and AVP levels from study (n= 5)
      and age-matched control (n= 6) lambs. Subsequently, lambs were euthanized, and
      the pituitary and hypothalamus were processed for the determination of pituitary
      AVP content by radioimmunoassay, and AVP gene expression by Northern analysis. In
      response to water restriction, maternal plasma osmolality significantly increased
      (306 +/- 1.1 to 326 +/- 1.2 mOsm/kg, P< 0.001). At the age of 28 days, plasma
      sodium level was higher in study (prenatally dehydrated) than control lambs
      (144.6 +/- 0.4 vs 142.6 +/- 0.3,P< 0.05). Study lambs had higher plasma AVP
      concentrations than the control lambs (4.1 +/- 0.4 vs 1.7 +/- 0.4 pg/ml,P< 0.05).
      Similarly, total pituitary AVP content was higher in thein utero hypertonic lambs
      than in the control lambs (6.5 +/- 1.0 vs 2.8 +/-1.2 microg, P< 0.05). However,
      there was no difference in hypothalamic AVP mRNA levels between the two groups.
      The present study demonstrates that chronic maternal and fetal plasma
      hypertonicity has prolonged effects on pituitary and plasma AVP, as well as
      plasma sodium in neonatal lambs, providing further evidence suggesting prenatal
      imprinting of osmoregulation through at least 1 month of age.

PMID- 12524472
TI  - Carbon monoxide as an attenuator of vasoconstriction in piglet cerebral
      arterioles.
AB  - Carbon monoxide (CO) is an endogenous dilator in the newborn cerebral
      circulation. The present study addressed the hypothesis that endogenous CO
      attenuates pial arteriolar vasoconstriction caused by hypocapnia, platelet
      activating factor, and elevated blood pressure. Experiments used anesthetized
      piglets with implanted, closed cranial windows. Topical application of a metal
      porphyrin inhibitor of heme oxygenase was used to inhibit production of CO.
      Chromium mesopophyrin increased vasoconstriction in response to hypocapnia. The
      constrictor response to a topical stimulus, platelet activating factor, was also
      increased by application of chromium mesoporphyrin. Inhibition of heme oxygenase
      did not constrict pial arterioles in normotensive newborn pigs (mean arterial
      pressure of about 70 mmHg), but did constrict pial arterioles of piglets with
      experimentally induced increases in arterial pressure (mean arterial pressure
      greater than 90 mmHg). In fact, pial arterioles of normotensive piglets
      transiently dilated to chromium mesoporphyrin, whereas those of hypertensive
      piglets progressively constricted during 10 min of chromium mesoporphyrin
      treatment. Therefore, inhibition of heme oxygenase augments cerebral
      vasoconstriction in response to several very different constrictor stimuli. These
      data suggest endogenous CO attenuates vasoconstrictor responses in the newborn
      cerebral circulation.

PMID- 12524473
TI  - Dietary conjugated linoleic acid decreased cachexia, macrophage tumor necrosis
      factor-alpha production, and modifies splenocyte cytokines production.
AB  - The effect of conjugated linoleic acid (CLA) on macrophage functions were studied
      in vitro, in vivo, and ex vivo. In RAW macrophage cell line, CLA (mixed isomers)
      was shown to inhibit lipopolysaccharide (LPS)-stimulated tumor necrosis factor
      alpha (TNF-alpha) production. Two CLA isomers, c9,t11 and t10,c12, were tested on
      RAW cells and it was found that the c9,t11 was the isomer responsible for the
      inhibition of LPS-induced TNF-alpha production. BALB/c mice were used to
      determine the effect of dietary CLA on body weight wasting and feed intake after
      LPS injection. CLA was protective against LPS-induced body weight wasting and
      anorexia. Plasma TNF-alpha levels after LPS injection were lower in the CLA group
      compared with the corn oil-fed control group 2 hr post-LPS injection. In a
      separate experiment, 30 mice were fed a CLA-supplemented diet or a corn oil
      supplemented diet for 6 weeks and peritoneal resident macrophages were obtained
      for measuring TNF-alpha and nitric oxide production after in vitro exposure to
      interferon-gamma (IFN-gamma) and/or LPS. TNF-alpha production was not found to be
      different in peritoneal macrophages from mice fed the dietary treatments, but
      less nitric oxide was produced in macrophages from CLA-fed mice upon stimulation
      when compared with macrophages from control-fed mice. Splenocytes were also
      collected from the mice fed the dietary treatments and stimulated to produce
      cytokines in culture. Supernatant was used to run cytokine enzyme-linked
      immunoabsorbant assays. Interleukin-4 (IL-4) was decreased in CLA-fed mice when
      splenocytes were stimulated with concanavalin A (Con A) for 44 hr; however, IL-2
      and the IL-2-to-IL-4 ratio were elevated.

PMID- 12524474
TI  - Heme oxygenase in the rat ovary: immunohistochemical localization and possible
      role in steroidogenesis.
AB  - The objectives of this study were to determine if heme oxygenase (HO), which
      catalyzes the degradation of heme and the formation of carbon monoxide (CO), is
      localized in the rat ovary and, if so, to determine if hemin (a substrate for HO)
      or chromium mesoporphyrin (CrMP, an inhibitor of HO), alter basal or gonadotropin
      induced steroidogenesis. The hypothesis was that CO produced endogenously by HO
      suppresses steroid hormone production by the ovary similar to the action of
      nitric oxide. For the histological localization of HO, sections of ovaries
      obtained from mature Holtzman Sprague-Dawley rats were immunostained for two of
      the HO isoforms, HO-1 and HO-2. Theca cells and granulosa cells of follicles and
      luteal cells stained for HO-1, whereas the ovarian stroma showed a low intensity
      of staining. Theca, granulosa cells, and corpora lutea as well as the ovarian
      stroma exhibited HO-2 staining. HO-2 immunostaining appeared more intense for
      theca cells than granulosa cells. In the study of steroidogenesis, three daily
      injections of hemin stimulated basal- and gonadotropin-induced androstenedione
      and estradiol secretion from ovaries of pregnant mare serum gonadotropin-treated
      immature rats in vitro, but had no effect on progesterone production. A similar
      treatment with CrMP suppressed basal- and gonadotropin-induced secretion of
      progesterone and androstenedione, but had no effect on estradiol production.
      These data, taken together, show the existence of HO in the rat ovary and suggest
      a possible stimulatory role of endogenous CO in the production of ovarian
      steroids.

PMID- 12524475
TI  - Heme oxygenase in the rat anterior pituitary: immunohistochemical localization
      and possible role in gonadotropin and prolactin secretion.
AB  - The objectives of this study were to determine if heme oxygenase (HO), which
      catalyzes the degradation of heme and the formation of carbon monoxide (CO), is
      localized in the rat anterior pituitary and, if so, to determine if hemin (a
      substrate for HO) or chromium mesoporphyrin (CrMP) (an inhibitor of HO), alter
      pituitary gonadotropin and prolactin secretion. For localization of HO, sections
      of anterior pituitaries obtained from mature Holtzman Sprague-Dawley rats in
      different stages of the estrous cycle were immunostained for two of the HO
      isoforms, HO-1 and HO-2. The immunostaining for the inducible HO isoform (HO-1)
      was limited to discrete populations of pituitary cells, whereas the constitutive
      isoform (HO-2) had a more widespread distribution. The afternoon surge of
      leutinizing hormone (LH) in the plasma of ovariectomized, estradiol-treated rats
      was advanced by 2 hr after 7 days of treatment with CrMP (4 micro M/kg), and this
      effect was reversed when hemin (30 micro M/kg) was co-administered with CrMP. The
      afternoon follicle-stimulating hormone (FSH) surge was not affected by either
      treatment. In contrast, the afternoon prolactin (PRL) surge was completely
      blocked or delayed by CrMP treatment, and this effect was not reversed by hemin.
      In vitro perifusion of pituitary explants with CrMP also significantly reduced
      PRL release compared with secretion from untreated explants. In vitro
      gonadotropin-releasing hormone (GnRH)-stimulated FSH secretion was significantly
      increased from pituitary explants of ovariectomized, estradiol-treated rats
      treated in vivo with hemin but was unaffected by CrMP treatment, whereas GnRH
      stimulated LH release was not affected by hemin but was increased by CrMP
      treatment. In conclusion, this study demonstrates that HO exists in the rat
      anterior pituitary gland, and that a substrate and an inhibitor of this enzyme
      alter the secretion of gonadotropins and PRL.

PMID- 12524476
TI  - Effects of diabetes and gender on mechanical properties of the arterial system in
      rats: aortic impedance analysis.
AB  - We determined the effects of diabetes and gender on the physical properties of
      the vasculature in streptozotocin (STZ)-treated rats based on the aortic input
      impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age
      matched controls. Pulsatile aortic pressure and flow signals were measured and
      were then subjected to Fourier transformation for the analysis of aortic input
      impedance. Wave transit time was determined using the impulse response function
      of the filtered aortic input impedance spectra. Male but not female diabetic rats
      exhibited an increase in cardiac output in the absence of any significant changes
      in arterial blood pressure, resulting in a decline in total peripheral
      resistance. However, in each gender group, diabetes contributed to an increase in
      wave reflection factor, from 0.47 +/- 0.04 to 0.84 +/- 0.03 in males and from
      0.46 +/- 0.03 to 0.81 +/- 0.03 in females. Diabetic rats had reduced wave transit
      time, at 18.82 +/- 0.60 vs 21.34 +/- 0.51 msec in males and at 19.63 +/- 0.37 vs
      22.74 +/- 0.57 msec in females. Changes in wave transit time and reflection
      factor indicate that diabetes can modify the timing and magnitude of the wave
      reflection in the rat arterial system. Meanwhile, diabetes produced a fall in
      aortic characteristic impedance from 0.023 +/- 0.002 to 0.009 +/- 0.001
      mmHg/min/kg/ml in males and from 0.028 +/- 0.002 to 0.014 +/- 0.001
      mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished
      aortic characteristic impedance and wave transit time suggest that the muscle
      inactivation in diabetes may occur in aortas and large arteries and may cause a
      detriment to the aortic distensibility in rats with either sex. We conclude that
      only rats with male gender diabetes produce a detriment to the physical
      properties of the resistance arterioles. In spite of male or female gender,
      diabetes decreases the aortic distensibility and impairs the wave reflection
      phenomenon in the rat arterial system.

PMID- 12524477
TI  - Species comparison of methemoglobin reductase.
AB  - Methemoglobin (MHb) formation is effective in treating cyanide (CN) poisoning.
      Endogenous activity of the enzyme MHb reductase (MR) reflects the capacity to
      reduce MHb and thus represents a key factor for evaluating anti-CN efficacy of
      MHb formers. MR activity was measured in whole blood of nine animal species and
      was compared with human MR activity. The animals in this comparative study
      included seven nonhuman primate (NHP) species, the beagle dog, and the ferret.
      Although exhibiting higher MR activity than in humans, the rhesus and aotus NHPs'
      average MR activity was the closest to humans', with raw data from each NHP
      showing overlap with human raw data. The beagle dog, used extensively to study
      anti-CN characteristics of MHb formers, was the sole species that displayed MR
      activity lower than in humans, with no data overlap. Based on MR activity, the
      rhesus and aotus NHPs may each represent a more accurate model for predicting
      human responses to MHb formers. The data from this study provides a unique
      interspecies enzyme comparison, which should facilitate future rational
      development of anti-CN MHb formers.

PMID- 12524478
TI  - Determination of size distribution of elliptical microvessels from size
      distribution measurement of their section profiles.
AB  - In transmission electron microscopy, microvessels (MVs) are studied as profiles
      on ultrathin sections. To determine MV sizes from measurements made on MV
      profiles, an assumption must be made about MV shape, a circular cylinder being
      used to approximate the latter on limited lengths. However, this model is
      irrelevant in case MVs have some flatness. The elliptical cylinder model is
      preferable, although relationships between the cylinder profile (two-dimensional;
      2D) and its true (three-dimensional; 3D) sizes are not yet known. We have
      obtained the 2D/3D functions that express the relationships between such profile
      sizes as the minor radius (Y), major radius (X), axial ratio (X/Y), area (S), and
      perimeter (P) on the one hand, and the corresponding MV sizes (Y(0), X(0),
      X(0)/Y(0), S(0), and P(0)) on the other. The 2D/3D functions make it possible to
      derive elliptical MV sizes from section profile size distributions, probability
      density functions (PDFs) for the latter being determined. We have applied the
      2D/3D functions in studying axial ratios of thyroid hemocapillaries. A factual
      X/Y frequency histogram has been constructed and fitted by theoretical X/Y PDFs
      plotted for different sets of capillary sizes. The thyroid capillaries have been
      revealed to be clustered, 72.7% of them having X(0)/Y(0) approximately 1.6,
      17.6%, X(0)/Y(0) approximately 1.0, and 9.7%, X(0)/Y(0) approximately 3.2. The
      proposed technique is instrumental in precise modeling of microcirculatory
      network geometry.

PMID- 12524479
TI  - Cocoa flavonols and procyanidins promote transforming growth factor-beta1
      homeostasis in peripheral blood mononuclear cells.
AB  - Evidence suggests that certain flavan-3-ols and procyanidins (FP) can have a
      positive influence on cardiovascular health. It has been previously reported that
      FP isolated from cocoa can potentially modulate the level and production of
      several signaling molecules associated with immune function and inflammation,
      including several cytokines and eicosanoids. In the present study, we examined
      whether FP fractions monomers through decamers modulate secretion of the cytokine
      transforming growth factor (TGF)-beta(1) from resting human peripheral blood
      mononuclear cells (PBMC). A total of 13 healthy subjects were studied and grouped
      according to their baseline production of TGF-beta(1). When cells from
      individuals with low baseline levels of TGF-beta(1) (n = 7) were stimulated by
      individual FP fractions (25 microg/ml), TGF-beta(1) release was enhanced in the
      range of 15%-66% over baseline (P < 0.05; monomer, dimer, and tetramer). The low
      molecular-weight FP fractions (<or=pentamer) were more effective at augmenting
      TGF-beta(1) secretion than their larger counterparts (>or=hexamer), with the
      monomer and dimer inducing the greatest increases (66% and 68%, respectively). In
      contrast to the above, TGF-beta(1) secretion from high TGF-beta(1) baseline
      subjects (n = 6) was inhibited by individual FP fractions (P < 0.05; trimer
      through decamer). The inhibition was most pronounced with trimeric through
      decameric fractions (28%-42%), and monomers and dimers moderately inhibited TGF
      beta(1) release (17% and 23%, respectively). Given the vascular actions
      associated with TGF-beta(1), we suggest that in healthy individuals, homeostatic
      modulation of its production by FP offers an additional mechanism by which FP
      rich foods can potentially benefit cardiovascular health.

PMID- 12524480
TI  - Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone
      infusion during late gestation.
AB  - Glucocorticoids near term are known to upregulate many important enzyme systems
      prior to birth. Glutamate dehydrogenase (GDH) is a mitochondrial enzyme that
      catalyzes both the reversible conversion of ammonium nitrogen into organic
      nitrogen (glutamate production) and the oxidative deamination of glutamate
      resulting in 2-oxoglutarate. The activity of this enzyme is considered to be of
      major importance in the development of catabolic conditions leading to
      gluconeogenesis prior to birth. Ovine hepatic GDH mRNA expression and activity
      were determined in near-term (130 days of gestation, term 147 +/- 4 days) control
      and acutely dexamethasone-treated (0.07 mg(-1) hr(-1) for 26 hr) fetuses.
      Dexamethasone infusion had no effect on placental or fetal liver weights.
      Dexamethasone infusion for 26 hr significantly increased hepatic GDH mRNA
      expression. This increased GDH mRNA expression was accompanied by an increase in
      hepatic mitochondrial GDH activity, from 30.0 +/- 7.4 to 58.2 +/- 8.1 U GDH/U CS
      (citrate synthase), and there was a significant correlation between GDH mRNA
      expression and GDH activity. The generated ovine GDH sequence displayed
      significant similarity with published human, rat, and murine GDH sequence. These
      data are consistent with the in vivo studies that have shown a redirection of
      glutamine carbon away from net hepatic glutamate release and into the citric acid
      cycle through the forward reaction catalyzed by GDH, i.e., glutamate to
      oxoglutarate.

PMID- 12524483
TI  - [AIDS and the lung at the era of highly active antiretroviral therapies].

PMID- 12524484
TI  - [Animals, allergy, and asthma: what is the link?].

PMID- 12524485
TI  - [Sleep apnea syndrome: what do the general practitioners know?].

PMID- 12524486
TI  - [Analysis of induced sputum in the management of asthma: a valid technique, a
      service rendered by community pneumonologists].

PMID- 12524487
TI  - [Pneumonia back from abroad].

PMID- 12524488
TI  - [Early detection of bronchial carcinoma: a pending issue].

PMID- 12524489
TI  - [DEPISCAN--a pilot study to evaluate low dose spiral CT scanning as a screening
      method for bronchial carcinoma].
AB  - The outcome of collaboration between INSERM (National Institute for Health and
      Medical Research), SFR (French Radiological Society) and SPLF (French Language
      Society of Pneumology), DEPISCAN is a pilot study for a large randomised trial
      which aims to evaluate screening for broncho-pulmonary cancer by the low dose
      spiral CT scanner. The principal objective of this preliminary study is to test
      the feasibility of a randomised study comparing the CT scanner and the chest x
      ray in 1,000 smokers and ex-smokers aged over 50 and followed up for 2 years.
      Recruitment of subjects will be undertaken by 130 general practitioners based on
      14 hospital centres distributed throughout France. We will evaluate the safety of
      the patients and the effect of screening on their quality of life and their
      tobacco consumption as well as the economic and methodological aspects of the
      study.

PMID- 12524490
TI  - [Screening for bronchial carcinoma].
AB  - Bronchial carcinoma is the principal cause of cancer death. Unlike cancers of the
      breast and colon that are already the subject of screening programmes, proof has
      not yet been provided that screening for bronchial carcinoma is of value in terms
      of reduction in mortality. Technological improvements and the advent of low dose
      spiral CT scanning has lead to a recent renewal of interest in this subject. The
      first preliminary studies seem to indicate that 2/3 of bronchial carcinomas
      discovered by CT scanning are detected at an early stage. Other data suggest a
      possible improvement in survival of tumours discovered by screening. Nevertheless
      it is necessary to demonstrate that screening improves the survival of patients
      with bronchial carcinoma. The present consensus does not advocate mass screening
      by CT scanning but that high risk subjects should voluntarily participate in
      randomised controlled trials which alone will confirm or refute the validity of
      this approach.

PMID- 12524491
TI  - [Management strategy of pulmonary nodules].
AB  - Today pulmonary nodules are commonly detected by spiral CT but their evaluation
      and management remain a difficult task. The traditional approach, based on the
      principles of decision analysis, relies on estimating the probability of
      malignancy from risks factors assessed by history and morphological
      characteristics on chest radiographs and CT examinations. Use of non-invasive
      techniques such as PET and contrast-enhanced CT may decrease the number of
      invasive procedures performed for obtaining a histological diagnosis. A precise
      evaluation of nodule growth can be obtained from recent improvements in CT
      technology and may shorten the follow-up. The goal of this review, based on the
      consensus obtained in a multidisciplinary group, is to emphasize the recent
      advances on the topic and to propose guidelines.

PMID- 12524492
TI  - [Epidemiologic of primary bronchial carcinoma management in the general French
      hospital centers].
AB  - INTRODUCTION: The College of General Hospital Respiratory Physicians have
      conducted a study aimed at a better understanding of the details and modalities
      of management of patients suffering from bronchial carcinoma in general hospitals
      in France. MATERIALS AND METHODS: A prospective epidemiological study was carried
      out on all the new cases of histologically proven bronchial carcinoma seen in
      general hospitals in the year 2000. The data were collected by a standardised
      questionnaire. RESULTS: 137 centres of investigation identified 5 667 patients,
      mean age 64.3 years, of whom 16% were women. 7.2% of patients were non smokers
      (with an incidence of 32.3% non-smokers among the women) and 40.3% were ex
      smokers. Histologically 16.9% were small cell carcinomas, 40% squamous carcinomas
      (43.1% among the men, 23.4% among the women, p<0.0001), 30.1% adenocarcinomas
      (27.2% among the men, 45.3% among the women, p<0.0001). 77.1% of non small cell
      carcinomas were stages III and IV, and 66.8% of small cell carcinomas were
      disseminated, with no difference between the sexes. CONCLUSION: Respiratory
      physicians in general hospitals manage more than a quarter of the cases of
      bronchial carcinoma seen annually in France. The number of women affected is high
      with a significant percentage of non-smokers and adenocarcinomas.

PMID- 12524493
TI  - [Does the presence of a pet at home influence the prevalence of asthma and
      rhinitis?].
AB  - INTRODUCTION: Recent epidemiological studies have shown an increase in the
      prevalence of asthma and allergic diseases. Among aetiological factors, the
      domestic environment and, in particular, pet ownership may be a part of it. The
      relationship between severity of asthma and pets is still unclear. The aim of
      this study was to evaluate the relationship of asthma and rhinitis prevalence in
      teenagers with pet ownership. PATIENTS AND METHODS: ISAAC I studied 3,303
      teenagers (13-14 years old) in Bordeaux in 1994. They completed a written
      questionnaire about asthma, rhinitis, eczema and their domestic environment. Four
      groups (asthmatics, asthmatics with rhinitis, teenagers with only rhinitis and a
      control group without asthma and rhinitis) were studied. RESULTS: 4.6% had only
      asthma. 43.2% had only rhinitis. 10.3% had asthma and rhinitis, 41.7% had no
      allergic disease. 34.9% kept a cat and 79.4% allowed the cat to go inside. No
      difference was found between the four groups with regard cat, dog, bird or other
      pet ownership irrespective if the pet was kept in-doors or out doors. The
      prevalence of previous asthma was 45.8% and 50.3% for current asthma. No
      difference was found between the severity of asthma and pet ownership.
      CONCLUSIONS: This is an epidemiological study based on a written questionnaire.
      Furthermore there is no data on the presence of pets during the first year of
      life. However, our results suggest that pet ownership amongst asthma and rhinitis
      sufferers is not different to that in the group without allergic disease.

PMID- 12524494
TI  - [The sleep apnea syndrome: diagnosis and management in general practice. A
      descriptive survey of 579 French general practitioners].
AB  - General practitioners (GP's) should be the first to recognise the sleep
      apnoea/hypopnoea syndrome (SAHS) and could play a major role in the follow up of
      patients treated with continuous positive airways pressure (CPAP) at home. We
      have carried out a prospective study in order to evaluate the knowledge and
      diagnostic and therapeutic practice of GP's in relation to SAHS. 579 GP's agreed
      to participate in the study by means of a telephone questionnaire. Although
      daytime somnolence and the presence of apnoeas and snoring were the most
      frequently quoted clinical symptoms suggesting the diagnosis of SAHS, a
      combination of these symptoms was quoted in only one third of cases. On the other
      hand the complications of SAHS were not well known by GP's as only 25% of them
      mentioned the possibility of cardiovascular complications; cerebrovascular
      accidents and arterial hypertension being quoted by only 15% and 8.8%
      respectively. With regard to the follow up of patients treated with CPAP more
      than 50% of GP's did not know the minimum duration of ventilation required and
      60% did not understand the method of function. These results, which emphasise the
      underestimation of SAHS and its complications, confirm the need to develop an
      educational strategy specifically for GP's in an attempt to improve the diagnosis
      of this disorder and to allow them to take part in the management and monitoring
      of treatment with CPAP.

PMID- 12524495
TI  - [Induced sputum as a new approach of the assessment of inflammation in asthma].
AB  - Asthma is an inflammatory condition. Traditionally bronchoalveolar lavage and
      bronchial biopsies obtained by bronchoscopy have been used to demonstrate
      inflammation. Induced-sputum is a non-invasive, reliable, reproducible and safer
      technique for monitoring inflammatory activity in patients with asthma. Studies
      have shown that induced-sputum measures aspects of inflammation distinct to that
      measured by bronchoalveolar lavage or bronchial biopsies. Numerous studies have
      suggested that induced-sputum is a potentially useful tool for early diagnosis of
      exacerbation, monitoring of therapy, identification of the lowest effective dose
      and assessing compliance in asthmatics. In this respect, we suggest that this
      test can be routinely used in the management of difficult asthmatics.

PMID- 12524496
TI  - [Acute pulmonary infections in elderly patients in institutions].
AB  - The high incidence of lower lung infections in elderly subjects in institutions
      is responsible for an increase in mortality both as the result of the infection
      itself and of the deterioration of pre-existing conditions. The multiple
      pathology of these elderly patients living in institutions necessitates
      particularly detailed diagnosis and management. While the pneumococcus remains
      the predominant organism the percentage of infections with staphylococci and Gram
      negative bacteria is higher than among younger subjects. The initial severity
      should be assessed by clinical and pathological criteria in the same way as the
      response to treatment. Transfer to hospital is often necessary. Among
      preventative measures anti-influenzal and anti-pneumococcal vaccines are
      recommended and reimbursed at 100%.

PMID- 12524497
TI  - [Validation study of a diagnostic test: a guide to critical appraisal. Report on
      the role of endobronchial biopsy in the diagnosis of sarcoidosis].
AB  - The case for endobronchial biopsy in the diagnosis of sarcoidosis: Faced with the
      continuous development of new diagnostic tests, the clinician needs to be able to
      critically assess their value and their clinical applicability. Using a practical
      example, the performance of endobronchial biopsy in diagnosing sarcoidosis, this
      review provides a guide for critically appraising a study evaluating a diagnostic
      test. The three main steps described are: 1) assessment of the validity of the
      results based on the scientific methods used; 2) analysis of the results with
      reference to sensitivity, specificity, predictive value, likelihood ratio, and
      precision of the diagnostic test in question; 3) determination of whether the
      results are applicable to an individual patient or to a specific patient
      population.

PMID- 12524498
TI  - [The pathophysiological role of smooth muscle cells in bronchial inflammation].
AB  - Airway smooth muscle cells (SMC) have been implicated in the pathophysiology of
      bronchial inflammation. SMC can be considered a target of the inflammatory
      reaction. This cell-type is capable of contraction, proliferation and mediator
      synthesis in response to various stimuli, in particular those associated with the
      inflammatory reaction. SMC can also be considered as an inflammatory cell-type.
      Cytokines and adhesion molecules released by SMC have an autocrine action and
      paracrine action on other cell-types, particularly those involved in
      inflammation, inducing chemotactism and cell adhesion. This interaction allows
      SMC to directly act on cells such as the T-lymphocyte, the eosinophil and the
      mast cell. SMC could therefore be a potential target of anti-inflammatory
      treatment.

PMID- 12524499
TI  - [Bilateral pleurisy and cardiac tamponade. A rare etiology: pancreatico-pleural
      fistula].
AB  - Pancreatico-pleural fistula is a rare complication of chronic pancreatitis. It
      commonly presents with small, but recurrent, pleural effusions. Pericarditis
      rarely occurs in this context. We report a case presenting with bilateral large
      pleural effusions associated with cardiac tamponade. The diagnosis was suspected
      on detection of high concentration of pancreatic enzyme in the pleural fluid and
      was confirmed by both endoscopic retrograde pancreatography and magnetic
      resonance pancreatography. Both examinations demonstrated a fistula and a
      calculus of the Wirsung duct. In addition, they identified a pancreas divisum, a
      congenital abnormality which can rarely lead to complications. The usual medical
      and endoscopic management of this condition failed and a surgical solution for
      the fistula was needed. This case is unique due to the dramatic presentation of
      this complication of pancreas divisum and to the complexity of treatment
      required.

PMID- 12524500
TI  - [High-frequency endobronchial electrocoagulation].

PMID- 12524501
TI  - [A rare cause of mediastinal mass].

PMID- 12524502
TI  - [Melioidosis: a cause of pneumonia to suspect in travellers back from Oceania].

PMID- 12524503
TI  - [Alveolar lipoproteinosis: polarized light microscopy should be systematic].

PMID- 12524507
TI  - The postdoctoral system under the spotlight.

PMID- 12524508
TI  - A live issue and a moving target.

PMID- 12524509
TI  - Computing with DNA.

PMID- 12524510
TI  - Back to the roots.

PMID- 12524513
TI  - Think like a bacterium. Conference on bacterial neural networks.

PMID- 12524514
TI  - A molecular dissection of nuclear function. Conference on the dynamic nucleus:
      questions and implications.

PMID- 12524515
TI  - Initiating inhibition. Control of epidermal cell patterning in plants.

PMID- 12524516
TI  - A rotary pumping model for helicase function of MCM proteins at a distance from
      replication forks.
AB  - We propose an integrated model for eukaryotic DNA replication to explain the
      following problems: (1) How is DNA spooled through fixed sites of replication?
      (2) What and where are the helicases that unwind replicating DNA? (3) Why are the
      best candidates for replicative helicases, namely mini-chromosome maintenance
      (MCM) proteins, not concentrated at the replication fork? (4) How do MCM proteins
      spread away from loading sites at origins of replication? We draw on recent
      discoveries to argue that the MCM hexameric ring is a rotary motor that pumps DNA
      along its helical axis by simple rotation, such that the movement resembles that
      of a threaded bolt through a nut, and we propose that MCM proteins act at a
      distance from the replication fork to unwind DNA. This model would place DNA
      replication in a growing list of processes, such as recombination and virus
      packaging, that are mediated by ring-shaped ATPases pumping DNA by helical
      rotation.

PMID- 12524517
TI  - NF-kappaB activation by protein kinase C isoforms and B-cell function.
AB  - B cells are essential to the immune response in health and disease. Results from
      knockout (KO) mice for different members of the nuclear factor-kappaB (NF-kappaB)
      family have highlighted the importance of this transcription factor in B cell
      development and function. The recent generation of additional KO mice for
      adapters and kinases implicated in NF-kappaB activation, including several
      protein kinase C isoforms, has provided new insights into the roles of these
      proteins in B cell signalling. These studies have also given rise to a number of
      important questions that must be answered with further experimentation to
      establish accurately the signalling pathways that regulate B-cell function
      through NF-kappaB.

PMID- 12524518
TI  - Strategies for helicase recruitment and loading in bacteria.
AB  - DNA replication initiation in prokaryotes and eukaryotes requires the recruitment
      and loading of a helicase at the replication origin. To subsequently unwind the
      double-stranded DNA, the helicase must be properly positioned on the separated
      DNA strands. Several studies have revealed similarities and differences in the
      mechanisms used by different autonomously replicating DNA elements (replicons)
      for recruitment and activation of the appropriate helicase. Of particular
      interest are plasmid replicons that are adapted for replication in diverse
      bacterial hosts and are therefore intriguingly able to exploit the helicases of
      distantly related bacterial species. The different molecular mechanisms by which
      replicons recruit and load helicases are only just beginning to be understood.

PMID- 12524519
TI  - Human cytomegalovirus prevents replication licensing by inhibiting MCM loading
      onto chromatin.
AB  - To allow DNA replication only once per cell cycle, origins of replication are
      reactivated ('licensed') during each G1 phase. Licensing is facilitated by
      assembly of the pre-replicative complex (pre-RC) at origins that concludes with
      loading the mini-chromosome maintenance (MCM) complex onto chromatin. Here we
      show that a virus exploits pre-RC assembly to selectively inhibit cellular DNA
      replication. Infection of quiescent primary fibroblasts with human
      cytomegalovirus (HCMV) induces all pre-RC factors. Although this is sufficient to
      assemble the MCM-loading factors onto chromatin, as it is in serum-stimulated
      cells, the virus inhibits loading of the MCM complex itself, thereby prematurely
      abrogating replication licensing. This provides a new level of control in pre-RC
      assembly and a mechanistic rationale for the unusual HCMV-induced G1 arrest that
      occurs despite the activation of the cyclin E-dependent transcription programme.
      Thus, this particularly large virus might thereby secure the supply with
      essential replication factors but omit competitive cellular DNA replication.

PMID- 12524520
TI  - The Gam protein of bacteriophage Mu is an orthologue of eukaryotic Ku.
AB  - Mu bacteriophage inserts its DNA into the genome of host bacteria and is used as
      a model for DNA transposition events in other systems. The eukaryotic Ku protein
      has key roles in DNA repair and in certain transposition events. Here we show
      that the Gam protein of phage Mu is conserved in bacteria, has sequence homology
      with both subunits of Ku, and has the potential to adopt a similar architecture
      to the core DNA-binding region of Ku. Through biochemical studies, we demonstrate
      that Gam and the related protein of Haemophilus influenzae display DNA binding
      characteristics remarkably similar to those of human Ku. In addition, we show
      that Gam can interfere with Ty1 retrotransposition in Saccharomyces cerevisiae.
      These data reveal structural and functional parallels between bacteriophage Gam
      and eukaryotic Ku and suggest that their functions have been evolutionarily
      conserved.

PMID- 12524521
TI  - The yeast counterparts of human 'MELAS' mutations cause mitochondrial dysfunction
      that can be rescued by overexpression of the mitochondrial translation factor EF
      Tu.
AB  - We have taken advantage of the similarity between human and yeast (Saccharomyces
      cerevisiae) mitochondrial tRNA(Leu)(UUR), and of the possibility of transforming
      yeast mitochondria, to construct yeast mitochondrial mutations in the gene
      encoding tRNA(Leu)(UUR) equivalent to the human A3243G, C3256T and T3291C
      mutations that have been found in patients with the neurodegenerative disease
      MELAS (for mitochondrial 'myopathy, encephalopathy, lactic acidosis and stroke
      like episodes'). The resulting yeast cells (bearing the equivalent mutations
      A14G, C26T and T69C) were defective for growth on respiratory substrates,
      exhibited an abnormal mitochondrial morphology, and accumulated mitochondrial DNA
      deletions at a very high rate, a trait characteristic of severe mitochondrial
      defects in protein synthesis. This effect was specific at least in the pathogenic
      mutation T69C, because when we introduced A or G instead of C, the respiratory
      defect was absent or very mild. All defective phenotypes returned to normal when
      the mutant cells were transformed by multicopy plasmids carrying the gene
      encoding the mitochondrial elongation factor EF-Tu. The ability to create and
      analyse such mutated strains and to select correcting genes should make yeast a
      good model for the study of tRNAs and their interacting partners and a practical
      tool for the study of pathological mutations and of tRNA sequence polymorphisms.

PMID- 12524522
TI  - Trithorax interacts with type 1 serine/threonine protein phosphatase in
      Drosophila.
AB  - The catalytic subunit of type 1 serine/threonine protein phosphatase (PP1c) was
      shown to bind trithorax (TRX) in the yeast two-hybrid system. Interaction between
      PP1c and TRX was confirmed in vivo by co-immunoprecipitation from Drosophila
      extracts. An amino-terminal fragment of TRX, containing a putative PP1c-binding
      motif, was shown to be sufficient for binding to PP1c by in vitro glutathione S
      transferase pull-down assays using recombinant protein and fly extracts
      expressing epitope tagged PP1c. Disruption of the PP1c-binding motif abolished
      binding, indicating that this motif is necessary for interaction with PP1. On
      polytene chromosomes, PP1c is found at many discrete bands, which are widely
      distributed along the chromosomes. Many of the sites that stain strongly for PP1c
      correspond to sites of TRX, consistent with a physical association of PP1c with
      chromatin-bound TRX. Homeotic transformations of haltere to wing in flies mutant
      for trx are dominantly suppressed by PP1c mutants, indicating that PP1c not only
      binds TRX, but is a physiologically relevant regulator of TRX function in vivo.

PMID- 12524523
TI  - DmMyD88 controls dorsoventral patterning of the Drosophila embryo.
AB  - MyD88 is an adapter protein in the signal transduction pathway mediated by
      interleukin-1 (IL-1) and Toll-like receptors. A Drosophila homologue of MyD88
      (DmMyD88) was recently shown to be required for the Toll-mediated immune
      response. In Drosophila, the Toll pathway was originally characterized for its
      role in the dorsoventral patterning of the embryo. We found that, like Toll,
      DmMyD88 messenger RNA is maternally supplied to the embryo. Here we report the
      identification of a new mutant allele of DmMyD88, which generates a protein
      lacking the carboxy-terminal extension, normally located downstream of the
      Toll/IL-1 receptor domain. Homozygous mutant female flies lay dorsalized embryos
      that are rescued by expression of a transgenic DmMyD88 complementary DNA. The
      DmMyD88 mutation blocks the ventralizing activity of a gain-of-function Toll
      mutation. These results show that DmMyD88 encodes an essential component of the
      Toll pathway in dorsoventral pattern formation.

PMID- 12524524
TI  - The ligand-sensitive gate of a potassium channel lies close to the selectivity
      filter.
AB  - Potassium channels selectively conduct K(+) ions across cell membranes and have
      key roles in cell excitability. Their opening and closing can be spontaneous or
      controlled by membrane voltage or ligand binding. We used Ba(2+) as a probe to
      determine the location of the ligand-sensitive gate in an inwardly rectifying
      K(+) channel (Kir6.2). To a K(+) channel, Ba(2+) and K(+) are of similar sizes,
      but Ba(2+) blocks the pore by binding within the selectivity filter. We found
      that internal Ba(2+) could still access its binding site when the channel was
      shut, which indicates that the ligand-sensitive gate lies above the Ba(2+)-block
      site, and thus within or above the selectivity filter. This is in marked contrast
      to the voltage-dependent gate of K(V) channels, which is located at the
      intracellular mouth of the pore.

PMID- 12524525
TI  - A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel
      assembly.
AB  - Mutations in KCNQ K(+) channel genes underlie several human pathologies. KCNQ
      alpha-subunits form either homotetramers or hetero-oligomers with a restricted
      subset of other KCNQ alpha-subunits or with KCNE beta-subunits. KCNQ1 assembles
      with KCNE beta-subunits but not with other KCNQ alpha-subunits. By contrast,
      KCNQ3 interacts with KCNQ2, KCNQ4 and KCNQ5. Using a chimaeric strategy, we show
      that a cytoplasmic carboxy-terminal subunit interaction domain (sid) suffices to
      transfer assembly properties between KCNQ3 and KCNQ1. A chimaera (KCNQ1-sid(Q3))
      carrying the si domain of KCNQ3 within the KCNQ1 backbone interacted with KCNQ2,
      KCNQ3 and KCNQ4 but not with KCNQ1. This interaction was shown by enhancement of
      KCNQ2 currents, testing for dominant-negative effects of pore mutants,
      determining its effects on surface expression and co-immunoprecipitation
      experiments. Conversely, a KCNQ3-sid(Q1) chimaera no longer affects KCNQ2 but
      interacts with KCNQ1. We conclude that the si domain suffices to determine the
      subunit specificity of KCNQ channel assembly.

PMID- 12524526
TI  - Lymphotoxin and lipopolysaccharide induce NF-kappaB-p52 generation by a co
      translational mechanism.
AB  - The 'classical' NF-kappaB activation pathway proceeds via IkappaB kinase (IKK)
      beta/gamma-mediated phosphorylation, induced ubiquitination and the degradation
      of small IkappaBs. An alternative, NF-kappaB-inducing kinase and IKK-alpha
      dependent pathway, which stimulates the processing of NF-kappaB2/p100, has
      recently been suggested. However, no physiological stimulus has been shown to
      trigger the activation of this pathway. Here we demonstrate that persistent
      stimulation with lymphotoxin beta (LT-beta) receptor agonists or
      lipopolysaccharide (LPS), but not with interleukin-1beta, tumour necrosis factor
      alpha or 12-O-tetradecanoylphorbol-13-acetate, induces the generation of p52 DNA
      binding complexes by activating the processing of the p100 precursor. Induction
      of p52 DNA-binding activity is delayed in comparison with p50/p65 complexes and
      depends on de novo protein synthesis. p100 is constitutively and inducibly
      polyubiquitinated, and both ubiquitination and p52 generation are coupled to
      continuing p100 translation. Thus, both LT-beta receptor agonists and LPS induce
      NF-kappaB/p100 processing to p52 at the level of the ribosome.

PMID- 12524527
TI  - Cyclic AMP is sufficient for triggering the exocytic recruitment of aquaporin-2
      in renal epithelial cells.
AB  - The initial response of renal epithelial cells to the antidiuretic hormone
      arginine vasopressin (AVP) is an increase in cyclic AMP. By applying
      immunofluorescence, cell membrane capacitance and transepithelial water flux
      measurements we show that cAMP alone is sufficient to elicit the antidiuretic
      cellular response in primary cultured epithelial cells from renal inner medulla,
      namely the transport of aquaporin-2 (AQP2)-bearing vesicles to, and their
      subsequent fusion with, the plasma membrane (AQP2 shuttle). The AQP2 shuttle is
      evoked neither by AVP-independent Ca(2+) increases nor by AVP-induced Ca(2+)
      increases. However, clamping cytosolic Ca(2+) concentrations below resting levels
      at 25 nM inhibited exocytosis. Exocytosis was confined to a slow monophasic
      response, and readily releasable vesicles were missing. Analysis of endocytic
      capacitance steps revealed that cAMP does not decelerate the retrieval of AQP2
      from the plasma membrane. Our data suggest that cAMP initiates an early step,
      namely the transport of AQP2-bearing vesicles towards the plasma membrane, and do
      not support a regulatory function for Ca(2+) in the AQP2 shuttle.

PMID- 12524528
TI  - The two alpha-tubulin isotypes in budding yeast have opposing effects on
      microtubule dynamics in vitro.
AB  - The yeast Saccharomyces cerevisiae has two genes for alpha-tubulin, TUB1 and
      TUB3, and one beta-tubulin gene, TUB2. The gene product of TUB3, Tub3, represents
      approximately 10% of alpha-tubulin in the cell. We determined the effects of the
      two alpha-tubulin isotypes on microtubule dynamics in vitro. Tubulin was purified
      from wild-type and deletion strains lacking either Tub1 or Tub3, and parameters
      of microtubule dynamics were examined. Microtubules containing Tub3 as the only
      alpha-tubulin isotype were less dynamic than wild-type microtubules, as shown by
      a shrinkage rate and catastrophe frequency that were about one-third of that for
      wild-type microtubules. Conversely, microtubules containing Tub1 as the only
      alpha-tubulin isotype were more dynamic than wild-type microtubules, as shown by
      a shrinkage rate that was 50% higher and a catastrophe frequency that was 30%
      higher than those of wild-type microtubules. The results suggest that a role of
      Tub3 in budding yeast is to control microtubule dynamics.

PMID- 12524529
TI  - Correction of disease-associated exon skipping by synthetic exon-specific
      activators.
AB  - Differential exon use is a hallmark of alternative splicing, a prevalent
      mechanism for generating protein isoform diversity. Many disease-associated
      mutations also affect pre-mRNA splicing, usually causing inappropriate exon
      skipping. SR proteins are essential splicing factors that recognize exonic
      splicing enhancers and drive exon inclusion. To emulate this function of SR
      proteins, we designed small chimeric effectors comprising a minimal synthetic RS
      domain covalently linked to an antisense moiety that targets an exon by Watson
      Crick base pairing. Here we show that such synthetic effectors can mimic the
      functions of SR proteins and specifically restore wild type splicing when
      directed to defective BRCA1 or SMN2 pre-mRNA transcripts. This general approach
      can be used as a tool to investigate splicing mechanisms and modulate alternative
      splicing of specific genes, and as a therapeutic strategy to correct splicing
      defects responsible for numerous diseases.

PMID- 12524530
TI  - Structural analysis of the yeast SWI/SNF chromatin remodeling complex.
AB  - Elucidating the mechanism of ATP-dependent chromatin remodeling is one of the
      largest challenges in the field of gene regulation. One of the missing pieces in
      understanding this process is detailed structural information on the enzymes that
      catalyze the remodeling reactions. Here we use a combination of subunit radio
      iodination and scanning transmission electron microscopy to determine the subunit
      stoichiometry and native molecular weight of the yeast SWI/SNF complex. We also
      report a three-dimensional reconstruction of yeast SWI/SNF derived from electron
      micrographs.

PMID- 12524531
TI  - Active site electronic structure and dynamics during metalloenzyme catalysis.
AB  - Zinc-dependent enzymes play important roles in many cellular processes.
      Assignment of their reaction mechanisms is often a subject of debate because the
      zinc ion is silent in several spectroscopic techniques. We have combined time
      resolved X-ray absorption spectroscopy, pre-steady state kinetics and
      computational quantum chemistry to study the active site zinc ion of bacterial
      alcohol dehydrogenase during single substrate turnover. We detect a series of
      alternations in the coordination number and structure of the catalytic zinc ion
      with concomitant changes in metal-ligand bond distances. These structural changes
      are reflected in the effective charge of the metal ion. The present work
      emphasizes the flexibility of catalytic zinc sites during catalysis and provides
      novel mechanistic insights into alcohol dehydrogenase catalysis.

PMID- 12524532
TI  - Nickel coordination is regulated by the DNA-bound state of NikR.
AB  - The uptake of nickel in Escherichia coli and other microorganisms is
      transcriptionally regulated by the NikR repressor or its homologs. Here we report
      the structure of the high-affinity nickel-binding site in NikR and show that it
      responds dramatically to DNA binding. X-ray absorption spectroscopy reveals that
      nickel in the holo-NikR protein is bound in a novel four-coordinate planar site
      consisting of two histidines, one additional O- or N-donor ligand and one S-donor
      ligand. Site-directed mutation of His87, His89, Cys95 or Glu97 in NikR to alanine
      eliminates high-affinity nickel binding and abolishes DNA binding but maintains
      stable protein folding. An unanticipated feature of the NikR structure is that
      the nickel coordination responds to DNA binding. A six-coordinate nickel site
      composed of O- or N-donor ligands, but lacking cysteine, forms when NikR binds to
      operator DNA. Because nickel binding and DNA binding are mediated by different
      domains within NikR, a communication link between the two domains is implicated,
      consistent with the finding that the nickel-binding site in a fragment
      corresponding to the C-terminal domain of NikR is structurally distinct from that
      found in holo-NikR.

PMID- 12524533
TI  - Progranulin is a mediator of the wound response.
AB  - Annually, 1.25 million individuals suffer burns in the United States and 6.5
      million experience chronic skin ulcers, often from diabetes, pressure or venous
      stasis. Growth factors are essential mediators of wound repair, but their success
      as therapeutics in wound treatment has, so far, been limited. Therefore, there is
      a need to identify new wound-response regulatory factors, but few have appeared
      in recent years. Progranulin (also called granulin or epithelin precursor,
      acrogranin or PC-derived growth factor) is a growth factor involved in
      tumorigenesis and development. Peptides derived from progranulin have been
      isolated from inflammatory cells, which led to suggestions that progranulin gene
      products are involved in the wound response, but this remains undemonstrated. We
      report that in murine transcutaneous puncture wounds, progranulin mRNA is
      expressed in the inflammatory infiltrate and is highly induced in dermal
      fibroblasts and endothelia following injury. When applied to a cutaneous wound,
      progranulin increased the accumulation of neutrophils, macrophages, blood vessels
      and fibroblasts in the wound. It acts directly on isolated dermal fibroblasts and
      endothelial cells to promote division, migration and the formation of capillary
      like tubule structures. Progranulin is, therefore, a probable wound-related
      growth factor.

PMID- 12524534
TI  - Reciprocal regulation of inflammation and lipid metabolism by liver X receptors.
AB  - Macrophages have important roles in both lipid metabolism and inflammation and
      are central to the pathogenesis of atherosclerosis. The liver X receptors (LXRs)
      are established mediators of lipid-inducible gene expression, but their role in
      inflammation and immunity is unknown. We demonstrate here that LXRs and their
      ligands are negative regulators of macrophage inflammatory gene expression.
      Transcriptional profiling of lipopolysaccharide (LPS)-induced macrophages reveals
      reciprocal LXR-dependent regulation of genes involved in lipid metabolism and the
      innate immune response. In vitro, LXR ligands inhibit the expression of
      inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase
      (COX)-2 and interleukin-6 (IL-6) in response to bacterial infection or LPS
      stimulation. In vivo, LXR agonists reduce inflammation in a model of contact
      dermatitis and inhibit inflammatory gene expression in the aortas of
      atherosclerotic mice. These findings identify LXRs as lipid-dependent regulators
      of inflammatory gene expression that may serve to link lipid metabolism and
      immune functions in macrophages.

PMID- 12524535
TI  - Peyer's patch is the essential site in initiating murine acute and lethal graft
      versus-host reaction.
AB  - Acute graft-versus-host disease (a-GVHD) is initiated primarily by
      immunologically competent cytotoxic T cells (CTLs) that express anti-host
      specificities. However, the host lymphoid compartment in which these precursor
      CTLs are initially stimulated remains unclear. Here we show that gut Peyer's
      patches (PPs) are required to activate anti-host CTL responses in a well
      characterized murine acute graft-versus-host reaction (a-GVHR) model, involving
      transfer of parent lymphocytes into F1 hybrid recipients. The a-GVHR was
      prevented when recruitment of donor T cells into PP was interrupted either by
      disrupting the gene encoding chemokine receptor CCR5 or by blocking integrin
      alpha(4)beta(7)-MAdCAM-1 (mucosal vascular addressin) interactions. Mice
      deficient for PPs failed to develop a-GVHD in two models of disease induction.
      Thus, blockade of CTL generation in PPs might offer new strategies for
      circumventing a-GVHD.

PMID- 12524536
TI  - Impaired thymic development in mouse embryos deficient in apoptotic DNA
      degradation.
AB  - Apoptosis is often accompanied by the degradation of chromosomal DNA. Caspase
      activated DNase (CAD) is an endonuclease that is activated in dying cells,
      whereas DNase II is present in the lysosomes of macrophages. Here, we show that
      CAD(-/-) thymocytes did not undergo apoptotic DNA degradation. But, when
      apoptotic cells were phagocytosed by macrophages, their DNA was degraded by DNase
      II. The thymus of DNase II(-/-)CAD(-/-) embryos contained many foci carrying
      undigested DNA and the cellularity was severely reduced due to a block in T cell
      development. The interferon-beta gene was strongly up-regulated in the thymus of
      DNase II(-/-)CAD(-/-) embryos, suggesting that when the DNA of apoptotic cells is
      left undigested, it can activate innate immunity leading to defects in thymic
      development.

PMID- 12524537
TI  - Chromatin remodeling and extragenic transcription at the MHC class II locus
      control region.
AB  - In vivo, a wild-type pattern of major histocompatibility complex (MHC) class II
      expression requires a locus control region (LCR). Whereas the role of promoter
      proximal MHC class II regulatory sequences is well established, the function of
      the distal LCR remained obscure. We show here that this LCR is bound by the MHC
      class II-specific transactivators regulatory factor X (RFX) and class II
      transactivator (CIITA). Binding of these factors induces long-range histone
      acetylation, RNA polymerase II recruitment and the synthesis of extragenic
      transcripts within the LCR. The finding that RFX and CIITA regulate the function
      of the MHC class II LCR reveals an unexpected degree of complexity in the
      mechanisms controlling MHC class II gene expression.

PMID- 12524538
TI  - CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage
      commitment.
AB  - The relative importance of the cytokine milieu versus cytolytic T lymphocyte
      associated antigen 4 (CTLA-4) and T cell receptor signal strength on T cell
      differentiation remains unclear. Here we have generated mice deficient for signal
      transducer and activator of transcription 6 (STAT6) and CTLA-4 to determine the
      role of CTLA-4 in cytokine-driven T cell differentiation. CTLA-4-deficient T
      cells bypass the need for STAT6 in the differentiation of T helper type 2 (T(H)2)
      cells. T(H)2 differentiation of cells deficient for both STAT6 and CTLA-4 is
      accompanied by induction of GATA-3 and the migration of T(H)2 cells to peripheral
      tissues. CTLA-4 deficiency also affects the balance of the nuclear factors NFATc1
      and NFATc2, and enhances activation of NF-kappaB. These results suggest that CTLA
      4 has a critical role in T cell differentiation and that STAT6-dependent T(H)2
      lineage commitment and stabilization can be bypassed by increasing the strength
      of signaling through the T cell receptor.

PMID- 12524539
TI  - Cleaving the oxidative repair protein Ape1 enhances cell death mediated by
      granzyme A.
AB  - The cytolytic T lymphocyte protease granzyme A (GzmA) initiates a caspase
      independent cell death pathway. Here we report that the rate-limiting enzyme of
      DNA base excision repair, apurinic endonuclease-1 (Ape1), which is also known as
      redox factor-1 (Ref-1), binds to GzmA and is contained in the SET complex, a
      macromolecular complex of 270-420 kDa that is associated with the endoplasmic
      reticulum and is targeted by GzmA during cell-mediated death. GzmA cleaves Ape1
      after Lys31 and destroys its known oxidative repair functions. In so doing, GzmA
      may block cellular repair and force apoptosis. In support of this, cells with
      silenced Ape1 expression are more sensitive, whereas cells overexpressing
      noncleavable Ape1 are more resistant, to GzmA-mediated death.

PMID- 12524540
TI  - iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human.
AB  - We have previously shown that ASPP1 and ASPP2 are specific activators of p53; one
      mechanism by which wild-type p53 is tolerated in human breast carcinomas is
      through loss of ASPP activity. We have further shown that 53BP2, which
      corresponds to a C-terminal fragment of ASPP2, acts as a dominant negative
      inhibitor of p53 (ref. 1). Hence, an inhibitory form of ASPP resembling 53BP2
      could allow cells to bypass the tumor-suppressor functions of p53 and the ASPP
      proteins. Here, we characterize such a protein, iASPP (inhibitory member of the
      ASPP family), encoded by PPP1R13L in humans and ape-1 in Caenorhabditis elegans.
      iASPP is an evolutionarily conserved inhibitor of p53; inhibition of iASPP by RNA
      mediated interference or antisense RNA in C. elegans or human cells,
      respectively, induces p53-dependent apoptosis. Moreover, iASPP is an oncoprotein
      that cooperates with Ras, E1A and E7, but not mutant p53, to transform cells in
      vitro. Increased expression of iASPP also confers resistance to ultraviolet
      radiation and to cisplatin-induced apoptosis. iASPP expression is upregulated in
      human breast carcinomas expressing wild-type p53 and normal levels of ASPP.
      Inhibition of iASPP could provide an important new strategy for treating tumors
      expressing wild-type p53.

PMID- 12524541
TI  - Meta-analysis of genetic association studies supports a contribution of common
      variants to susceptibility to common disease.
AB  - Association studies offer a potentially powerful approach to identify genetic
      variants that influence susceptibility to common disease, but are plagued by the
      impression that they are not consistently reproducible. In principle, the
      inconsistency may be due to false positive studies, false negative studies or
      true variability in association among different populations. The critical
      question is whether false positives overwhelmingly explain the inconsistency. We
      analyzed 301 published studies covering 25 different reported associations. There
      was a large excess of studies replicating the first positive reports,
      inconsistent with the hypothesis of no true positive associations (P < 10(-14)).
      This excess of replications could not be reasonably explained by publication bias
      and was concentrated among 11 of the 25 associations. For 8 of these 11
      associations, pooled analysis of follow-up studies yielded statistically
      significant replication of the first report, with modest estimated genetic
      effects. Thus, a sizable fraction (but under half) of reported associations have
      strong evidence of replication; for these, false negative, underpowered studies
      probably contribute to inconsistent replication. We conclude that there are
      probably many common variants in the human genome with modest but real effects on
      common disease risk, and that studies using large samples will convincingly
      identify such variants.

PMID- 12524542
TI  - Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells
      during mouse embryogenesis.
AB  - Zfp148 belongs to a large family of C2H2-type zinc-finger transcription factors.
      Zfp148 is expressed in fetal germ cells in 13.5-d-old (E13.5) mouse embryos. Germ
      line transmission of mutations were not observed in chimeric Zfp148(+/-) mice,
      and some of these mice completely lacked spermatogonia. The number of primordial
      germ cells in Zfp148(+/-) tetraploid embryos was normal until E11.5, but declined
      from E11.5 to E13.5 and continued to decline until few germ cells were present at
      E18.5. This phenotype was not rescued by wild-type Sertoli or stromal cells, and
      is therefore a cell-autonomous phenotype. These results indicate that two
      functional alleles of Zfp148 are required for the normal development of fetal
      germ cells. Recent studies have shown that Zfp148 activates p53, which has an
      important role in cell-cycle regulation. Primordial germ cells stop proliferating
      at approximately E13.5, which correlates with induction of phosphorylation of p53
      and its translocation to the nucleus. Phosphorylation of p53 is impaired in
      Zfp148(+/-) embryonic stem cells and in fetal germ cells from chimeric Zfp148(+/
      ) embryos. Thus, Zfp148 may be required for regulating p53 in the development of
      germ cells.

PMID- 12524543
TI  - Retroelements containing introns in diverse invertebrate taxa.
AB  - We report that two structurally similar transposable elements containing reverse
      transcriptase (RT), Penelope in Drosophila virilis and Athena in bdelloid
      rotifers, have proliferated as copies containing introns. The ability of Penelope
      like elements (PLEs) to retain introns, their separate phylogenetic placement and
      their peculiar structural features make them a novel class of eukaryotic
      retroelements.

PMID- 12524544
TI  - Genome-wide analysis of RNA-protein interactions illustrates specificity of the
      mRNA export machinery.
AB  - Nuclear export of mRNA is mediated by a complex machinery of RNA-binding proteins
      that recognizes and routes mRNAs through a messenger ribonucleoprotein (mRNP)
      network. The full spectrum of mRNA cargoes for any dedicated mRNA export factor
      is unknown. We identified the mRNAs that bind two conserved yeast mRNA export
      factors, Yra1 (refs. 1-5) and Mex67 (refs. 6,7), on a genome-wide scale and
      determined their level of binding. Yra1 and Mex67 bind approximately 1,000 and
      1,150 mRNAs, respectively, corresponding to almost 20% of the yeast genome and
      roughly 36% of all transcriptional events each. The binding level of Yra1 targets
      is related to their transcriptional frequency, but that of Mex67 targets is not.
      Yra1-bound transcripts are enriched in mRNAs that are regulated by a number of
      transcription factors. Yra1- and Mex67-bound populations also show enrichment of
      mRNAs encoding distinct functional classes of proteins, some of which are
      regulated by these transcription factors. We determined that one such
      transcription factor, Abf1 (refs. 8-10), associates with Yra1. These results
      indicate a previously unidentified specificity of mRNA export factors, which
      coordinates the export of transcriptionally co-regulated, functional classes of
      transcripts, perhaps through interactions with the transcriptional machinery.

PMID- 12524545
TI  - Activation of NR1/NR2B NMDA receptors.
AB  - N-methyl-D-aspartate (NMDA) receptors are highly expressed in the central nervous
      system and are involved in excitatory synaptic transmission as well as synaptic
      plasticity. Despite considerable structural and biophysical research, the
      mechanism behind activation of the NMDA receptor is still poorly understood. By
      analyzing patch clamp recordings of one channel activated by glutamate, we
      determined the burst structure and open probability for recombinant rat NR1/NR2B
      receptors. We used partial agonists at the glutamate and glycine binding sites to
      show that at least two kinetically distinct subunit-associated conformational
      changes link co-agonist binding to the opening of the NMDA receptor pore. These
      data suggest that NR1 and NR2B subunits, respectively, undergo a fast and slow
      agonist-dependent conformational change that precedes opening of the pore. We
      propose a new working model of receptor activation that can account for
      macroscopic as well as microscopic NMDA receptor properties.

PMID- 12524546
TI  - Tissue plasminogen activator in the amygdala is critical for stress-induced
      anxiety-like behavior.
AB  - Although neuronal stress circuits have been identified, little is known about the
      mechanisms that underlie the stress-induced neuronal plasticity leading to fear
      and anxiety. Here we found that the serine protease tissue-plasminogen activator
      (tPA) was upregulated in the central and medial amygdala by acute restraint
      stress, where it promoted stress-related neuronal remodeling and was subsequently
      inhibited by plasminogen activator inhibitor-1 (PAI-1). These events preceded
      stress-induced increases in anxiety-like behavior of mice. Mice in which the tPA
      gene has been disrupted did not show anxiety after up to three weeks of daily
      restraint and showed attenuated neuronal remodeling as well as a maladaptive
      hormonal response. These studies support the idea that tPA is critical for the
      development of anxiety-like behavior after stress.

PMID- 12524547
TI  - Plasticity in human sound localization induced by compressed spatial vision.
AB  - Auditory and visual target locations are encoded differently in the brain, but
      must be co-calibrated to maintain cross-sensory concordance. Mechanisms that
      adjust spatial calibration across modalities have been described (for example,
      prism adaptation in owls), though rudimentarily in humans. We quantified the
      adaptation of human sound localization in response to spatially compressed vision
      (0.5x lenses for 2-3 days). This induced a corresponding compression of auditory
      localization that was most pronounced for azimuth (minimal for elevation) and was
      restricted to the visual field of the lenses. Sound localization was also
      affected outside the field of visual-auditory interaction (shifted centrally, not
      compressed). These results suggest that spatially modified vision induces
      adaptive changes in adult human sound localization, including novel mechanisms
      that account for spatial compression. Findings are consistent with a model in
      which the central processing of sound location is encoded by recruitment rather
      than by a place code.

PMID- 12524548
TI  - Active cyclin B1-Cdk1 first appears on centrosomes in prophase.
AB  - Cyclin B1-Cdk1 is the key initiator of mitosis, but when and where activation
      occurs has not been precisely determined in mammalian cells. Activation may occur
      in the nucleus or cytoplasm, as just before nuclear envelope breakdown, Polo-like
      kinase1 (Plk1) is proposed to phosphorylate cyclin B1 in its nuclear export
      sequence (NES), to trigger rapid nuclear import. We raised phospho-specific
      antibodies against cyclin B1 that primarily recognise the active form of the
      complex. We show that cyclin B1 is initially phosphorylated on centrosomes in
      prophase and that Plk1 phosphorylates cyclin B1, but not in the NES. Furthermore,
      phosphorylation by Plk1 does not cause cyclin B1 to move into the nucleus. We
      conclude that cyclin B1-Cdk1 is first activated in the cytoplasm and that
      centrosomes may function as sites of integration for the proteins that trigger
      mitosis.

PMID- 12524549
TI  - Lipopeptide detergents designed for the structural study of membrane proteins.
AB  - The structural study of membrane proteins requires detergents that can
      effectively mimic lipid bilayers, and the choice of detergent is often a
      compromise between detergents that promote protein stability and detergents that
      form small micelles. We describe lipopeptide detergents (LPDs), a new class of
      amphiphile consisting of a peptide scaffold that supports two alkyl chains, one
      anchored to each end of an alpha-helix. The goal was to design a molecule that
      could self-assemble into a cylindrical micelle with a rigid outer hydrophilic
      shell surrounding an inner lipidic core. Consistent with this design, LPDs self
      assemble into small micelles, can disperse phospholipid membranes, and are
      gentle, nondenaturing detergents that preserve the structure of the membrane
      proteins in solution for extended periods of time. The LPD design allows for a
      membrane-like packing of the alkyl chains in the core of the molecular
      assemblies, possibly explaining their superior properties relative to traditional
      detergents in stabilizing membrane protein structures.

PMID- 12524550
TI  - Engineering increased vitamin C levels in plants by overexpression of a D
      galacturonic acid reductase.
AB  - L-Ascorbic acid (vitamin C) in fruits and vegetables is an essential component of
      human nutrition. Surprisingly, only limited information is available about the
      pathway(s) leading to its biosynthesis in plants. Here, we report the isolation
      and characterization of GalUR, a gene from strawberry that encodes an NADPH
      dependent D-galacturonate reductase. We provide evidence that the biosynthesis of
      L-ascorbic acid in strawberry fruit occurs through D-galacturonic acid, a
      principal component of cell wall pectins. Expression of GalUR correlated with
      changing ascorbic acid content in strawberry fruit during ripening and with
      variations in ascorbic acid content in fruit of different species of the genus
      Fragaria. Reduced pectin solubilization in cell walls of transgenic strawberry
      fruit with decreased expression of an endogenous pectate lyase gene resulted in
      lower ascorbic acid content. Overexpression of GalUR in Arabidopsis thaliana
      enhanced vitamin C content two- to threefold, demonstrating the feasibility of
      engineering increased vitamin C levels in plants using this gene.

PMID- 12524551
TI  - Kindling fluorescent proteins for precise in vivo photolabeling.
AB  - Photobleaching of green fluorescent protein (GFP) is a widely used approach for
      tracking the movement of subcellular structures and intracellular proteins.
      Although photobleaching is a powerful technique, it does not allow direct
      tracking of an object's movement and velocity within a living cell. Direct
      tracking becomes possible only with the introduction of a photoactivated
      fluorescent marker. A number of previous studies have reported optically induced
      changes in the emission spectra of fluorescent proteins. However, the ideal
      photoactivated fluorescent marker should be a nonfluorescent tag capable of
      "switching on" (i.e., becoming fluorescent) in response to irradiation by light
      of a particular wavelength, intensity, and duration. In this report, we generated
      a mutant of Anemonia sulcata chromoprotein asCP. The mutant protein is capable of
      unique irreversible photoconversion from the nonfluorescent to a stable bright
      red fluorescent form ("kindling"). This "kindling fluorescent protein" (KFP1) can
      be used for precise in vivo photolabeling to track the movements of cells,
      organelles, and proteins. We used KFP1 for in vivo cell labeling in mRNA
      microinjection assays to monitor Xenopus laevis embryo development and to track
      mitochondrial movement in mammalian cells.

PMID- 12524552
TI  - A high-throughput nonisotopic protein truncation test.
AB  - Nonsense or frameshift mutations, which result in a truncated gene product, are
      prevalent in a variety of disease-related genes, including APC (implicated in
      colorectal cancer), BRCA1 and BRCA2 (breast and ovarian cancer), PKD1 (polycystic
      kidney disease), NF1 and NF2 (neurofibromatosis), and DMD (Duchenne muscular
      dystrophy). Such chain-truncating mutations can be detected using the protein
      truncation test (PTT). This test is based on cell-free transcription and
      translation of either PCR-amplified portions of the target gene or RT-PCR
      amplified target mRNA, followed by analysis of the product(s) for shortened
      polypeptide fragments. However, conventional PTT is not easily adapted to high
      throughput applications because it involves SDS-PAGE followed by autoradiography
      or western blotting. It is also subject to human error, as it relies on visual
      inspection to detect the mobility of shifted bands. To overcome these
      limitations, we have developed a high-throughput solid-phase protein truncation
      test (HTS-PTT). HTS-PTT uses a combination of misaminoacylated tRNAs, which
      incorporate affinity tags for surface capture of the cell-free expressed protein
      fragments, and specially designed PCR primers, which introduce N- and C-terminal
      markers for measuring the relative level of shortened polypeptides produced by
      the chain-truncation mutation. After cell-free translation of the protein
      fragments, capture and detection are accomplished in a single well using a
      standard 96-well microtiter plate enzyme-linked immunosorbent assay (ELISA)
      format and chemiluminescence readout. We demonstrate the use of the technique to
      detect chain-truncation mutations in the APC gene using DNA or RNA from cancer
      cell lines as well as DNA of individuals diagnosed with familial adenomatous
      polyposis (FAP). HTS-PTT can also provide a high-throughput method for
      noninvasive colorectal cancer screening when used in conjunction with methods of
      enriching and amplifying low-abundance mutant DNA.

PMID- 12524553
TI  - Conversion of embryonic stem cells into neuroectodermal precursors in adherent
      monoculture.
AB  - Mouse embryonic stem (ES) cells are competent for production of all fetal and
      adult cell types. However, the utility of ES cells as a developmental model or as
      a source of defined cell populations for pharmaceutical screening or
      transplantation is compromised because their differentiation in vitro is poorly
      controlled. Specification of primary lineages is not understood and consequently
      differentiation protocols are empirical, yielding variable and heterogeneous
      outcomes. Here we report that neither multicellular aggregation nor coculture is
      necessary for ES cells to commit efficiently to a neural fate. In adherent
      monoculture, elimination of inductive signals for alternative fates is sufficient
      for ES cells to develop into neural precursors. This process is not a simple
      default pathway, however, but requires autocrine fibroblast growth factor (FGF).
      Using flow cytometry quantitation and recording of individual colonies, we
      establish that the bulk of ES cells undergo neural conversion. The neural
      precursors can be purified to homogeneity by fluorescence activated cell sorting
      (FACS) or drug selection. This system provides a platform for defining the
      molecular machinery of neural commitment and optimizing the efficiency of
      neuronal and glial cell production from pluripotent mammalian stem cells.

PMID- 12524556
TI  - Neuromyelitis optica.
AB  - Whether neuromyelitis optica (NMO), the co-occurrence of myelitis and optic
      neuritis, is a variant of multiple sclerosis (MS) or a unique disease is
      controversial. Distinct neuropathological features and a fulminant clinical
      course argue in favor of NMO as a distinct disease. However, the combination of
      neurological impairments of myelitis and optic neuritis occurs in patients with
      several inflammatory disorders, including multiple sclerosis and collagen
      vascular diseases. NMO is also associated with certain infectious diseases. The
      fact that the NMO phenotype occurs in a variety of disease states suggests that
      NMO does not represent a specific clinical entity. To better understand NMO and
      its associations with recognized diseases, a systematic review of the literature
      using MEDLINE was conducted. The history of NMO, its nosology, associations with
      other diseases, and current concepts of its pathogenesis and treatment is
      reviewed in this article.

PMID- 12524557
TI  - Vascular myelopathies-vascular malformations of the spinal cord: presentation and
      endovascular surgical management.
AB  - Spinal cord vascular malformations are often a cause of spinal myelopathy.
      Endovascular surgical approaches to spinal cord vascular malformations have
      become an important adjunct and often the primary treatment of these disorders.
      Spinal cord vascular malformations may be divided into several categories based
      on their anatomy and location. They may present with a wide range of symptoms far
      removed from the vascular pathology. Early recognition and treatment can effect a
      better outcome and often reverse presenting neurologic deficits. Emerging
      magnetic resonance imaging techniques allow visualization of flow voids, some
      vascular anatomy, and intramedullary pathology and are a good screening modality.
      However, selective diagnostic spinal angiography remains the study of choice to
      diagnose and elaborate on the anatomy and potential treatment protocols. Rapidly
      evolving endovascular techniques and technology are revolutionizing the treatment
      of vascular pathology in the central nervous system, either as an adjunct to
      traditional neurosurgical techniques or as definitive therapy. We review the
      diagnosis and treatment options for spinal cord vascular malformations.

PMID- 12524558
TI  - Infectious myelopathies.
AB  - Although infectious myelopathies are rare, timely and accurate diagnosis is
      essential to improving outcome. There are a number of organisms that may cause
      infectious myelopathies, including human immunodeficiency virus (HIV), human T
      cell lymphotropic virus type I (HTLV-I), herpesviruses, enteroviruses, Treponema
      pallidum, Mycobacterium tuberculosis, fungi, and parasites. Vacuolar myelopathy,
      the most common form of spinal cord disease in HIV-infected individuals, is
      underrecognized clinically. The failure to diagnose this condition is generally a
      consequence of the attribution of the lower extremity weakness and paresthesias
      to general debility and concomitant peripheral neuropathy. Tropical spastic
      paraparesis or HTLV-I-associated myelopathy involves the pyramidal tracts,
      chiefly at the thoracic level, and results in spastic lower extremity weakness
      and a spastic bladder. The herpesviruses (varicella-zoster, herpes simplex type
      2, cytomegalovirus) and the enteroviruses cause myelitis. Prior to the
      development of antibiotics, syphilis was the most frequent infectious cause of
      spinal cord disease. In light of the broad spectrum of pathogens that may affect
      the spinal cord and the variegate fashion in which these disorders may present,
      the physician must always consider an infectious etiology in the differential
      diagnosis for the patient presenting with myelopathy. This review addresses the
      infectious myelopathies by microorganism.

PMID- 12524559
TI  - Cervical myelopathy associated with degenerative spine disease and ossification
      of the posterior longitudinal ligament.
AB  - Cervical spondylotic myelopathy and ossification of the posterior longitudinal
      ligament are two of the leading etiologies of spinal cord damage in older
      patients. For most patients, the natural history is one of slow stepwise decline
      in function. With nonsurgical therapy only 30 to 50% of patients are expected to
      stabilize. Surgical options include anterior and posterior surgical
      decompression, spinal canal expansion, and spinal column stabilization.
      Prospective, randomized trials with standardized outcome measures are needed to
      clarify the benefit of surgery conclusively.

PMID- 12524560
TI  - Percutaneous vertebroplasty: an emerging therapy for vertebral compression
      fractures.
AB  - Osteoporosis is a debilitating disease that occurs in epidemic proportions in
      Western societies and has a large economic impact. Percutaneous vertebroplasty is
      successful in alleviating subacute and chronic pain caused by osteoporotic
      compression fractures and pathological vertebral fractures from tumor
      infiltration. The technique is safe and can be performed on an outpatient basis
      utilizing high-resolution fluoroscopy.

PMID- 12524561
TI  - Lumbar spinal stenosis.
AB  - Lumbar spinal stenosis refers to a diversity of conditions that decrease the
      total area of the spinal canal, lateral recesses, or neural foramina. Lumbar
      stenosis is a common disorder that may be present in isolation, with or without
      associated disk bulge or herniation, or can be associated with degenerative
      spondylolisthesis or scoliosis. Symptomatic lumbar spinal stenosis is
      characterized by neurogenic claudication and/or lumbar or sacral radiculopathy.
      Sixty percent to 85% of properly selected patients have a satisfactory
      symptomatic improvement with surgical treatment.

PMID- 12524562
TI  - Neuromuscular scoliosis: causes of deformity and principles for evaluation and
      management.
AB  - Scoliosis is commonly associated with a variety of neuromuscular disorders
      including conditions affecting upper and lower motor neurons as well as
      myopathies. Contained herein is a discussion of the spectrum of neuromuscular
      disorders that have been associated with scoliosis and related spinal
      deformities. Management, including surgical treatment in such patients, is
      summarized including indications, expectations, and impact on trunk balance,
      pulmonary function, and appearance.

PMID- 12524563
TI  - Rheumatoid arthritis of the cervical spine.
AB  - The cervical spine is commonly affected in patients with rheumatoid arthritis.
      Erosive synovitis of the joints of the cervical spine can result in various types
      of subluxations. Subluxations and pannus formation can cause significant pain and
      neurological compromise. Surgery is an important treatment modality for patients
      with intractable neck pain and neurological deficits. This article reviews the
      indications for surgery and surgical procedures of decompression and arthrodesis.
      New surgical fixation techniques have resulted in improved arthrodesis rates.
      However, long-term effects on adjacent motion segments is not known. The
      cornerstone of good surgical outcome remains careful selection of patients and
      appropriate choice of surgical decompression and fusion.

PMID- 12524564
TI  - The lumbar zygapophyseal (facet) joints: a role in the pathogenesis of spinal
      pain syndromes and degenerative spondylolisthesis.
AB  - The zygapophyseal joints in the lumbar spine are important structural components
      contributing to the stability of the lumbar motion segments. Pathology of the
      zygapophyseal joints in the lumbar spine may be a significant cause of low back
      pain and segmental instability within the lumbar spine. Management of pathology
      related to the zygapophyseal joints remains a difficult challenge for the
      physician caring for patients with spinal disorders. Future investigations with
      tissue engineering, ligamentous reconstructions, and intervertebral disc
      replacement or regeneration may have useful applications in the treatment of
      zygapophyseal joint pathology.

PMID- 12524565
TI  - Electrophysiological evaluation of root and spinal cord disease.
AB  - The electrophysiological evaluation of root or spinal cord disease is
      complementary to neuroimaging studies, providing information about functional
      rather than anatomical integrity and information that is important for diagnostic
      and prognostic purposes. The electrophysiological findings help to localize a
      lesion but are not pathognomonic of specific diseases. The findings may also
      provide insight into underlying physiological mechanisms that have been
      disrupted. A number of different electrophysiological techniques are now in
      widespread use. Each of these techniques provides different information and thus
      has distinct utility and limitations. The optimal evaluation of patients with
      root or spinal cord disease requires an understanding of how these techniques
      complement each other and depends on the individual clinical problem for which
      electrophysiological assessment is requested.

PMID- 12524566
TI  - Spine imaging.
AB  - Imaging of the vertebral column and spinal cord has evolved from plain film
      evaluation to computed tomography (CT), CT in conjunction with myelography, and
      most recently magnetic resonance imaging (MRI). Currently, MRI has essentially
      replaced other imaging modalities in evaluation of the spine because of its
      superiority in demonstrating anatomic detail and multiplanar capability. The
      following is a review of the various imaging modalities available and their
      application in the evaluation of common spinal disorders.

PMID- 12524567
TI  - Indications, techniques, and complications of lumbar interbody fusion.
AB  - Lumbar interbody arthrodesis is a surgical technique that results in fusion of
      the anterior column of the spine. The indications for this procedure have evolved
      over time, and current indications include spinal deformity, segmental
      instability, and discogenic low back pain. Arthrodesis in the interbody space can
      be accomplished through anterior or posterior approaches to the spine, and these
      techniques are discussed. Surgical approaches in performing an interbody
      arthrodesis can be complicated by nerve and vascular injury. Clinical outcome
      studies are important in better defining the role of lumbar interbody arthrodesis
      as a substitute for posterior fusion in the lumbar spine.

PMID- 12524568
TI  - Developing an action plan for integrating sleep topics into the medical school
      curriculum.
AB  - Sleep disorders are prevalent although they go unrecognized by clinicians,
      partially because of limited exposure to sleep medicine topics during medical
      school. Sleep topics can be integrated during both the preclinical and clinical
      years of the medical school curriculum by developing an integration strategy and
      action plan. Components of the action plan include examining the current medical
      school curriculum and the teaching infrastructure. Understanding curricular
      governance issues and how curriculum time is allocated will allow development of
      an effective integrative strategy. Sleep topics can be integrated into
      neuroscience, neuroanatomy, physiology, and behavioral science courses during the
      preclinical years. The sleep history and physical can be integrated into the
      physical diagnosis course. Sleep disorders can be introduced in clinical
      correlation courses. Integration strategies during the clinical years may include
      computer-based simulations. Careful assessment of the existing curriculum,
      curricular governance processes, and available educational resources will
      optimize the probability of successfully integrating sleep topics into the
      medical school curriculum.

PMID- 12524570
TI  - The misinterpretation of a non-REM sleep parasomnia as suicidal behavior in an
      adolescent.
AB  - We report a case of misinterpretation of a non-REM sleep parasomnia as suicidal
      behavior in an early adolescent. A 12-year-old female with a history of
      sleepwalking but no prior psychiatric diagnosis awoke in the middle of the night
      with a deep laceration to her neck and complete amnesia for the event. During the
      initial 2-week pediatric hospitalization, it was believed that the wound was
      intentionally self-inflicted despite patient claims and evidence to the contrary.
      The patient was placed on a psychiatric hold and transferred to an appropriate
      facility. We review rule-out diagnoses and evidence supporting this case as an
      example of a violent non-REM parasomnia resulting in self-injurious behavior.
      Diagnostic and treatment implications are discussed.

PMID- 12524569
TI  - Evidence for a positive association between pulmonary function and wine intake in
      a population-based study.
AB  - BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause
      mortality. Previous studies suggest that alcohol exposure may be linked to
      impaired pulmonary function through oxidant-antioxidant mechanisms. Alcoholic
      beverages may be an important source of oxidants and antioxidants. We analyzed
      the relation of beverage-specific alcohol intake with forced expiratory volume in
      one second (FEV1) and forced vital capacity (FVC) in a random sample of 1555
      residents of Western New York, USA. METHODS: We expressed pulmonary function as
      percent of predicted normal FEV1 (FEV1%) and FVC (FVC%) after adjustment for
      height, age, gender, and race. To obtain information on alcohol intake we used a
      questionnaire that reliably queries total alcohol and beverage-specific recent
      (past 30 days) and lifetime alcohol consumption. RESULTS: Using multiple linear
      regression analysis after adjustment for covariates (pack-years of smoking,
      weight, smoking status, education, nutritional factors, and for FEV1%, in
      addition, eosinophil count), we observed no significant correlation between total
      alcohol intake and lung function. However, we found positive associations of
      recent and lifetime wine intake with FEV1% and FVC%. When we analyzed white and
      red wine intake separately, the association of lung function with red wine was
      weaker than with white wine. CONCLUSION: While total alcohol intake was not
      related to lung function, wine intake showed a positive association with lung
      function. Although we cannot exclude residual confounding by healthier lifestyle
      in wine drinkers, differential effects of alcoholic beverages on lung health may
      exist.

PMID- 12524571
TI  - Pulmonary hypertension, sleep-disordered breathing, and beta blockers in heart
      failure patients.
AB  - Heart failure patients with pulmonary hypertension have a worse prognosis than
      heart failure patients with normal pulmonary artery pressures. Heart failure is
      usually considered the cause of the pulmonary hypertension when the two
      conditions coincide. However, there is evidence that sleep-disordered breathing
      may be responsible for the pulmonary hypertension in these patients, and the
      worsened outcomes in heart failure patients with pulmonary hypertension may be
      due to sleep-disordered breathing. In addition, sleep-disordered breathing may
      provide an explanation for the beneficial effect of beta-adrenergic antagonists
      in heart failure patients.

PMID- 12524573
TI  - Is it time for more than one constant positive airway pressure?
AB  - In the last 20 years, most sleep apnea patients have been treated more or less
      with one individual but constant level of continuous positive airway pressure
      (CPAP). New insights into CPAP- and bilevel PAP-therapy employing auto CPAP
      (APAP) devices might change our attitude. Readings of the pressure profiles from
      APAPs teach us that the needed pressure levels are constantly changing during the
      night and on a day-to-day basis as the patient's daily performance and alcohol
      consumption change too. A new approach to CPAP therapy is discussed.

PMID- 12524572
TI  - To breathe, perchance to sleep: sleep-disordered breathing and chronic insomnia
      among trauma survivors.
AB  - Standard psychiatric classification (DSM-IV-TR) traditionally attributes post
      traumatic sleep disturbance to a secondary or symptomatic feature of a primary
      psychiatric disorder. The DSM-IV-TR paradigm, however, has not been validated
      with objective sleep assessment technology, incorporated nosological constructs
      from the field of sleep disorders medicine, or adequately addressed the potential
      for post-traumatic stress disorder (PTSD) sleep problems to manifest as primary,
      physical disorders, requiring independent medical assessments and therapies. This
      paradigm may limit understanding of sleep problems in PTSD by promulgating such
      terms as "insomnia related to another mental disorder," a.k.a. "psychiatric
      insomnia." Emerging evidence invites a broader comorbidity perspective, based on
      recent findings that post-traumatic sleep disturbance frequently manifests with
      the combination of insomnia and a higher-than-expected prevalence of sleep
      disordered breathing (SDB). In this model of complex sleep disturbance, the
      underlying sleep pathophysiology interacts with PTSD and related psychiatric
      distress; and this relationship appears very important as demonstrated by
      improvement in insomnia, nightmares, and post-traumatic stress with successful
      SDB treatment, independent of psychiatric interventions. Continuous positive
      airway pressure treatment in PTSD patients with SDB reduced
      electroencephalographic arousals and sleep fragmentation, which are usually
      attributed to central nervous system or psychophysiological processes. Related
      findings and clinical experience suggest that other types of chronic insomnia may
      also be related to SDB. We hypothesize that an arousal-based mechanism, perhaps
      initiated by post-traumatic stress and/or chronic insomnia, may promote the
      development of SDB in a trauma survivor and perhaps other patients with chronic
      insomnia. We discuss potential neurohormonal pathways and neuroanatomatical sites
      that may be involved in this proposed interaction between insomnia and SDB.

PMID- 12524574
TI  - Neonatal intermittent hypoxia impairs dopamine signaling and executive
      functioning.
AB  - Mesotelencephalic dopamine (DA) pathways are exquisitely vulnerable to ischemic
      anoxic insult. These insults are known to produce long-term derangements in DA
      signaling and have been hypothesized to contribute, at least in part, to
      pathologic behaviors such as cerebral palsy, schizophrenia, and attention deficit
      hyperactivity disorder (ADHD). Whether modest intermittent hypoxia, such as that
      encountered with repetitive apneas in premature infants, contributes to
      clinically significant impairments in DA signaling, and how these impairments
      manifest at a systems level, is unknown. To address these voids there is a need
      to develop animal models emulating features of a common disorder of prematurity,
      namely, apnea with hypoxia. Behavioral traits exhibited by such models include
      disturbed sleep-wake architecture, excessive locomotion, and impaired working
      memory persisting 1 to 2 months post-insult. Western-blot analysis of expression
      patterns of proteins involved in DA signaling (e.g., DA and vesicular monoamine
      transporters, tyrosine hydroxylase, and D1 receptors) are consistent with that
      which might be expected from hyper- or hypodopaminergic functioning in DA
      responsive prefrontal cortex and striatal circuits, respectively. These novel
      observations suggest that intermittent hypoxia occurring during a period of
      critical brain development disrupts development of those mesotelencephalic
      pathways modulating the expression of sleep and wakefulness, locomotion, and
      executive functioning.

PMID- 12524575
TI  - [New "atypical" neuroleptics -- the emperor's new clothes?].

PMID- 12524576
TI  - [Schizophrenia in the German national paper Frankfurter Allgemeine Zeitung -- a
      didactic play].
AB  - The Basel Project on Psychiatry and the Printed Media has focussed on the role of
      the media in the development and enhancement of prejudice and stigma against the
      mentally ill. Analyzing the reporting of the German national paper Frankfurter
      Allgemeine Zeitung on schizophrenia we show a gap between the competent reporting
      on the illness schizophrenia and a devaluating use of schizophrenia as a
      metaphor. This is of special importance since almost three fifth of the
      identified articles (48 of 83) use schizophrenia as a metaphor.

PMID- 12524577
TI  - [Between assistance and opposition: relatives' coping strategies with obsessive
      compulsive patients].
AB  - OBJECTIVE AND METHOD: The aim of this study was to investigate the coping
      strategies of relatives of patients with obsessive-compulsive disorder. 22
      narrative interviews were analysed by a Grounded Theory approach. RESULTS: While
      parents in our investigation often try to educate their ill children, spouses
      focus on resources of the patient. Children seem to take a parent-role in
      interaction with the ill father or mother. DISCUSSION: Family members try to
      support patients in dealing with the illness. Therefore, different strategies to
      cope with OCD are developed, ranging between assisting in rituals and opposition
      to the symptoms.

PMID- 12524578
TI  - [In-patient suicide -- a comparison of psychiatric in-patient suicides versus a
      control group of inpatients from the same treatment era without suicide].
AB  - In our study we compare n = 64 in-patient suicides with a group of non-suicide in
      patients which received psychiatric treatment during the same period. The matched
      patient was the next admitted patient. We found a significantly higher portion of
      schizophrenic and depressed patients in the suicide group, whereas suicides
      showed more depressive symptoms, more suicidal ideations before the suicide and
      more subjective suffering. Suicides received more psychopharmaca.

PMID- 12524580
TI  - [Frontal dysfunctions in Huntington's disease -- neuropsychology and therapy].
AB  - Huntington's disease is a hereditary and progressive disease of the central
      nervous system. Sudden and irregular hyperkinesias are prominent.
      Psychopathological findings are very frequent and often proceed the decline of
      motor functions for years. Almost all the patients develop a dementia in later
      stages of the illness. This case study shows the treatment of a patient with
      Huntington's disease, verified by genetic analysis, with the atypical
      antipsychotic drug amisulpride. In this case the psychiatric disturbances and
      cognitive impairments were the only signs of the disease. The treatment showed an
      impressive improvement. Neuropsychological aspects of the disease are discussed.

PMID- 12524579
TI  - [Self-esteem and partner relationships of patients with bipolar affective
      disorder: a study of the interval personality with the Giessen-test].
AB  - The self-concept and the partner relationships of patients with bipolar affective
      disorder in remission were investigated with the Giessen-Test (GT, Beckmann et
      al. ) comparing the bipolar patients with unipolar depressive patients, a control
      group of orthopedic patients and the standard sample of the Giessen-Test. The new
      dimensions "self-esteem" and "near-to-object" were developed by means of the
      Giessen-Test items. Self-esteem was significantly lower in bipolar patients in
      remission than in the controls. The bipolar patients also described themselves as
      "more distant to others" than the controls. Bipolar and unipolar-depressive
      patients had a similar self-concept and view of their partner relationships. The
      results underline the importance of the regulation of self-esteem and the
      interpersonal dimension in the long-term course of bipolar affective disorder.
      Therapeutic implications are discussed.

PMID- 12524581
TI  - [Compulsive-obsessive disorder after severe head trauma: diagnosis and
      treatment].
AB  - An 18-year-old man suffered a severe head trauma from a car accident. Eight
      months later the patient had a good general state of health. But at this time he
      was referred to our psychiatric hospital and he reported increased checking
      compulsions and aggressive obsessions. In addition there was increased
      impulsivity. The patient was treated with an selective-serotonin-reuptake
      inhibitor (SSRI) and showed a clinical response. Obsessive-compulsive disorder
      (OCD) has rarely been described after traumatic brain injury. Clinical symptoms,
      neuropsychological dysfunctions, brain imaging and therapy are illustrated. The
      represented connections of the frontal brain lesions and OCD-symptoms with
      interventions in the serotonin system support the neurobiological hypotheses of
      the obsessive-compulsive disorder.

PMID- 12524582
TI  - Inferior extension of the groin flap based on the descending branch of the
      superficial circumflex iliac artery.
AB  - The authors present a groin flap which was extended inferiorly and included the
      descending branch of the superficial circumflex iliac artery (SCIA) as a new
      alternative technique. Little research has been previously done on the descending
      branch of the SCIA, but the authors found clinically that this small branch was
      consistently present, and decided to make use of it to extend the groin flap
      inferiorly. The procedure extending the groin flap was successfully applied in
      three patients, one with a degloving injury of the leg, and two with progressive
      hemifacial atrophy. The extended portion was elevated as an island flap based on
      the descending branch in the patient with the degloving injury. Results revealed
      that this technique added a new axial portion located on the upper median thigh
      to the vascular territory of the conventional groin flap, and could be used to
      make a two-island groin flap.

PMID- 12524583
TI  - Reverse-flow island flap from the thenar area of the hand.
AB  - A reverse-flow island flap from the thenar eminence of the hand was applied in
      six patients to treat palmar skin defects, and amputation injuries of the thumb.
      There was one female and five males, and the patients' ages at the time of
      surgery averaged 48 years. A 3 x 2 to 5 x 3.5-cm fasciocutaneous flap from the
      radial aspect of the thenar eminence, located over the abductor pollicis brevis
      muscle, was designed and transferred in a retrograde fashion, to cover skin and
      soft-tissue defects of the thumb. The flap was based on the superficial palmar
      branch of the radial artery and, in three patients, was made sensate by the
      palmar branch of the superficial radial nerve. Follow-up periods averaged 61
      months. The postoperative course was uneventful, and all the flaps survived
      without significant complications. The donor site was primarily closed in five
      patients, and one patient required flap coverage. A reverse island flap from the
      thenar area is easily elevated, contains durable fasciocutaneous structures, and
      has good color and texture, matching to the finger pulp. This flap offers a good
      alternative for reconstruction of palmar skin and soft-tissue defects of the
      thumb in selected patients.

PMID- 12524584
TI  - Medial brachial and antebrachial cutaneous nerve injuries: effect on outcome in
      revision cubital tunnel surgery.
AB  - Twenty patients with persistent symptoms of medial elbow pain after previous
      cubital tunnel surgery were evaluated during reoperation, for injury of the
      medial antebrachial and medial brachial cutaneous nerves at the time of
      reoperation. Abnormalities of the medial cutaneous nerves were found in 65
      percent of the patients. A neuroma was found in 40 percent of the patients. The
      neuromas were treated surgically by excision, stump cauterization, and relocation
      into muscle. All patients had revision release of the cubital tunnel. The results
      were analyzed after a mean follow-up of 26 months. The results of the 13 patients
      with injured cutaneous nerves tended to be worse ( p=0.065) than the results of
      seven patients without such findings.

PMID- 12524585
TI  - Minimal incision technique for sural nerve graft harvest: experience with 61
      patients.
AB  - Many different methods for harvesting the sural nerve have been described,
      including a single, long, longitudinal incision, multiple stair-step incisions,
      or use of a tendon stripper and endoscopic approach. Drawbacks of these methods
      may include unsightly donor-site scars, inadvertent transection of the nerve,
      prolonged operative time, and the need for special equipment. A new minimal
      incision technique of sural nerve harvesting that is simple and quick, causes
      minimal donor site morbidity, and preserves the integrity of the nerve is
      described.

PMID- 12524586
TI  - Neurotization of the frontal muscle after scalp replantation: case report.
AB  - A case of immediate replantation of an avulsed scalp by microvascular anastomosis
      is presented. Microvascular replantation of the scalp seems to offer significant
      social and psychological advantages over secondary reconstructive procedures. The
      significance of the case presented is the regaining of the motor neural function
      of the facial nerve after 38 months.

PMID- 12524587
TI  - Nerve repair using a composite graft of vein and denatured skeletal muscle:
      morphologic analysis.
AB  - Five groups of six rats each underwent sciatic resection, bridged with a 20-mm
      long graft. Five different types of graft were used: (1). vein; (2). fresh
      muscle; (3). denatured muscle; (4). vein and fresh muscle; and (5). vein and
      denatured muscle. Denaturation was obtained by dry thermal shock in a microwave
      oven. Morphologic analysis took place at 6 months. The macroscopic appearance of
      the graft was continuous in all type 4 and 5 animals. Morphometric analysis
      within the graft revealed a significantly greater number of fibers in type 3
      animals. Average fiber diameter and g ratio were higher, although not
      significantly, in type 5 animals. Distal to the graft, average fiber diameter and
      g ratio were significantly higher in type 5 rats. Denaturation by exposure to
      thermal shock significantly improves axonal regeneration, both quantitatively and
      qualitatively. The regeneration rate seems to be more rapid within denatured
      muscle. Denaturing muscle by exposure to thermal shock provides an excellent
      guide for axonal regrowth, but axonal leaks may occur. This problem is solved by
      a muscle-in-vein graft technique.

PMID- 12524588
TI  - Microvascular protection induced by late preconditioning was abolished in STZ
      induced acute diabetic rats.
AB  - The authors attempted to determine whether ischemic preconditioning (IPC) can
      provide microvascular protection in skeletal muscle of diabetic rats against
      injury from a subsequent (24 hr later) prolonged period of ischemia and
      reperfusion. Male Sprague Dawley rats weighting 80 to 100 g were injected
      intraperitoneally with either streptozotocin (STZ, 65 mg/kg) or vehicle (sodium
      citrate, pH 4.5). Rats with a fasting blood glucose level over 300 mg/dl 1 week
      after injection of STZ were considered acute diabetic. The cremaster muscle of
      the rats underwent 45 min of IPC and 24 hr later, 4 hr of warm ischemia followed
      by reperfusion (I/R). Four groups were compared: IPC in normal rats (n=8); sham
      IPC in normal rats (n=8); IPC in diabetic rats (n=6); and sham IPC in diabetic
      rats (n=4). Microvascular responses in the cremaster muscle to IPC were
      determined by measuring the diameter of feeding, terminal arterioles and
      capillary perfusion using intravital microscopy, and by the evaluation of the
      endothelium-dependent nitric oxide system in the terminal arterioles. The average
      diameter of the feeding and terminal arterioles, as well as capillary perfusion,
      were significantly decreased in diabetic animals, compared to normal animals.
      There was a significant endothelial dysfunction detected in the terminal
      arterioles of diabetic rats. Ischemic preconditioning provided significant
      microvascular protection against prolonged ischemia/reperfusion in normal rats,
      but not in diabetic rats. IPC-induced microvascular protection in the normal
      skeletal muscle was abolished in STZ-induced acute diabetic rats.

PMID- 12524589
TI  - Effect of sequence, timing of vascular anastomosis, and clamp removal on survival
      of microsurgical flaps.
AB  - The effects of the timing and order of clamp removal in microsurgical transplants
      were studied in rat groin skin flap and rat latissimus dorsi muscle flap models.
      Forty rats were divided into four groups. In Group 1, the arterial pedicle of the
      skin flap was anastomosed first, and the clamp was released after the anastomosis
      was completed. The venous pedicle was then repaired after inflow was restored. In
      Group 2, the venous pedicle of the skin flap was anastomosed first. The venous
      clamp was not released until completion of the arterial anastomosis. In Group 3,
      the arterial pedicle was anastomosed first in the muscle flap. The venous
      anastomosis was then performed after the arterial clamp was released. In Group 4,
      the venous pedicle was anastomosed first, and both clamps were released
      simultaneously. The blood perfusion of the skin flaps was examined after both
      clamps were released in Groups 1 and 2. The flap survival status was examined 5
      days postoperatively for skin flaps and at 3 days for muscle flaps. Skin flaps in
      an additional six rats were harvested for histology. The results showed that the
      flap blood flow for Group 1 was statistically significantly higher than for Group
      2 flaps in the first 20 min after reperfusion. There was no significant
      difference of flow between these two groups during the 30 to 90 min after
      reperfusion. The difference in survival rates for the four groups was not
      significant. Histology revealed extensive congestion in the flaps from Group 1
      after completion anastomoses, but the congestion was significantly decreased at 3
      hr following reperfusion. In conclusion, a brief venous stasis during
      anastomosis, after establishment of arterial inflow, is not detrimental to flap
      survival. The sequence of anastomosis will not affect outcome for either the
      cutaneous flap or the muscle flap models. Early flap perfusion was increased when
      the arterial anastomosis was performed first.

PMID- 12524590
TI  - Nerve repair at different angles of attachment: experiment in rats.
AB  - Sixteen rats underwent two procedures to test the efficacy of oblique vs.
      transverse nerve repair. On the left, the peroneal nerve was transected at an
      oblique angle (30-degree) with subsequent oblique end-to-end repair performed. On
      the right, the peroneal nerve was transected at a transverse angle (90-degree)
      with subsequent end-to-end repair. At 3.5 months postoperatively, the moist
      muscle weight of the extensor digitorum longus (EDL) and tetanic force were
      measured, and axons were counted in donor and recipient nerves. Muscle volume,
      tetanic force, and moist weight of EDL muscles were statistically significantly
      higher on the left side (oblique) than on the right (transverse). Histologic
      analysis with nerve axon counting of the recipient peroneal nerve revealed
      significantly more regenerated nerve fibers on the left than on the right. The
      authors concluded that oblique nerve repair enhances nerve-fiber sprouting from
      the proximal donor nerve by increasing the coapted surface area, thus improving
      muscle recovery.

PMID- 12524592
TI  - Anatomic considerations in aesthetic rhinoplasty.
AB  - A thorough understanding of nasal anatomy and physiology remains critical when
      approaching the nose to correct any contour or functional deficiencies. This
      article reviews the salient, anatomic features of the nose that are relevant to
      the rhinoplasty surgeon and further highlights basic surgical techniques that
      illustrate the anatomy germane to aesthetic surgery. The external anatomy of the
      nose is discussed in regard to the skin/ soft-tissue envelope, the superficial
      musculoaponeurtic system/muscular layer, the bony/ cartilaginous framework, and
      the dynamic tip-support mechanisms. The discussion of internal nasal anatomy
      concerns functional aspects of the nose, particularly the valvular components and
      the septum-turbinate complex.

PMID- 12524593
TI  - A systematic, graduated approach to rhinoplasty.
AB  - Rhinoplasty may be viewed as one of the most technically demanding procedures in
      facial plastic surgery and requires a level of sophistication derived from
      diligent study, repetitive execution, and critical review. During the
      preoperative evaluation, the physician must exercise a systematic approach that
      includes a thorough investigation into the psychological and physical aspects of
      the individual patient. A systematic, graduated approach should be undertaken in
      every rhinoplasty in which the three cornerstones-planning, simplicity, and
      flexibility-are recalled. Planning entails a thoughtful and critical analysis of
      what surgical techniques may be best enlisted to achieve the envisioned aesthetic
      effect. Simplicity argues in favor of performing only those surgical procedures
      needed to accomplish the task at hand to minimize the variables that arise from
      protracted, ill-defined surgery. Flexibility implies that the surgeon be capable
      of modifying his plan if unforeseen operative events disrupt the proposed course
      of action. All three principles reflect the authors' philosophy about the
      surgical approach to rhinoplasty, that is, the discretionary use of endonasal
      (nondelivery and delivery) and external incisions as warranted by circumstance.

PMID- 12524594
TI  - Structural grafting in rhinoplasty.
AB  - Many surgeons consider cosmetic rhinoplasty to be one of the most challenging
      facial plastic surgical procedures. Open-structure rhinoplasty allows for
      visualization of bony-cartilaginous deformities, preservation of nasal structural
      integrity, and precise nasal reshaping. The ultimate, external appearance of the
      nose is the sum of the interaction of the bony-cartilaginous skeleton and the
      skin soft-tissue envelope. This article describes the use of autologous,
      structural cartilage grafts in primary and secondary rhinoplasty. Emphasis is
      placed on the use of septal, auricular, and costal cartilage grafts to provide
      for a structurally sound skeletal framework and thereby a predictable
      postoperative result. Deformities of the middle and lower third of the nose are
      specifically addressed.

PMID- 12524595
TI  - Revision rhinoplasty.
AB  - Revision rhinoplasty requires sound judgment by both patient and surgeon.
      Detailed preoperative assessment facilitates proper patient selection. If the
      patient is deemed a favorable revision rhinoplasty candidate, both patient and
      surgeon must agree on the goals for and risks inherent in revision rhinoplasty.
      Thoughtfulness regarding the degree of aesthetic and functional correction
      desired by the patient and the corresponding intraoperative techniques required
      to achieve this correction must be contemplated prior to committing to revision
      rhinoplasty. Furthermore, the surgeon must feel confident that the surgical
      demands requested by the patient may be met and satisfaction achieved. A precise
      preoperative surgical plan minimizes intraoperative misadventures. Options for
      grafting materials should be discussed and agreed upon by both patient and
      surgeon preoperatively. Both patient and surgeon commit to long-term
      postoperative follow-up and the patience necessary for the eventual outcome to be
      realized.

PMID- 12524596
TI  - The Asian nose: augmentation rhinoplasty with L-shaped silicone implants.
AB  - Few procedures in facial plastic surgery elicit the controversy that surrounds
      augmentation of the Asian nose. Asian surgeons generally advocate augmentation
      with custom-fabricated silicone prostheses, a technique that Western surgeons,
      who strongly recommend autogenous material, condemn as inherently dangerous.
      Analysis of the evidence relating to augmentation with silicone prostheses
      suggests that there is little factual support for Western dogma and indicates
      that, when properly executed, augmentation with silicone implants yields reliable
      and consistently superior aesthetic results. A detailed blueprint for execution
      of augmentation rhinoplasty with custom- fabricated silicone implants is
      provided.

PMID- 12524597
TI  - Correction of the cleft-lip nasal deformity.
AB  - Correction of the cleft-lip nasal deformity is a difficult task that requires a
      clear understanding of the associated complex anatomic abnormalities. These
      deformities tend to accentuate as nasal growth continues. Primary tip rhinoplasty
      in the unilateral deformity improves nasal tip symmetry and decreases the need
      for intermediate surgery. Intermediate rhinoplasty in the bilateral deformity is
      performed when nasal tip projection is markedly diminished. In both the
      unilateral and bilateral deformity, definitive rhinoplasty utilizing the open
      structure rhinoplasty approach allows maximum exposure for placement of
      structural grafts to improve tip projection, definition, support, and function.
      In this article, the pathologic anatomy of the unilateral and bilateral cleft
      nasal deformity is described. The philosophy and timing of repair are discussed.
      Finally, the techniques used by the authors to address both the aesthetic and
      functional problems are outlined.

PMID- 12524599
TI  - Perfect storm or perfect opportunity? Addressing the crisis in oral and
      maxillofacial surgery education.

PMID- 12524598
TI  - Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome
      locus (BBS1).
AB  - Bardet-Biedl syndrome (BBS) is a genetic disorder with the primary features of
      obesity, pigmentary retinopathy, polydactyly, renal malformations, mental
      retardation, and hypogenitalism. Patients with BBS are also at increased risk for
      diabetes mellitus, hypertension, and congenital heart disease. BBS is known to
      map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3
      q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although these loci were all mapped on
      the basis of an autosomal recessive mode of inheritance, it has recently been
      suggested-on the basis of mutation analysis of the identified BBS2, BBS4, and
      BBS6 genes-that BBS displays a complex mode of inheritance in which, in some
      families, three mutations at two loci are necessary to manifest the disease
      phenotype. We recently identified BBS1, the gene most commonly involved in Bardet
      Biedl syndrome. The identification of this gene allows for further evaluation of
      complex inheritance. In the present study we evaluate the involvement of the BBS1
      gene in a cohort of 129 probands with BBS and report 10 novel BBS1 mutations. We
      demonstrate that a common BBS1 missense mutation accounts for approximately 80%
      of all BBS1 mutations and is found on a similar genetic background across
      populations. We show that the BBS1 gene is highly conserved between mice and
      humans. Finally, we demonstrate that BBS1 is inherited in an autosomal recessive
      manner and is rarely, if ever, involved in complex inheritance.

PMID- 12524600
TI  - Meta-analysis of surgical treatments for temporomandibular articular disorders.
AB  - PURPOSE: Temporomandibular joint articular disorders may cause severe pain and
      dysfunction. We addressed the following questions. Can any surgical procedures
      effectively treat these disorders? If so, which procedures are most effective?
      MATERIALS AND METHODS: We performed meta-analyses of surgical trial results to
      determine whether certain surgical procedures are effective in specific patient
      groups. To compensate for the lack of parallel control groups in published
      studies and for the improvement that has been observed in untreated patients, we
      used historical data from nonsurgical trials to derive 3 estimates of historical
      control group improvement (0%, 37.5%, and 75%). To our knowledge, this is the
      first meta-analytic evaluation of surgical treatments for temporomandibular joint
      disorders. RESULTS: Among patients refractory to nonsurgical therapies, surgical
      arthrocentesis and arthroscopy were effective for patients with disc displacement
      without reduction at all assumed control group improvement rates. Disc
      repair/repositioning had a statistically significant effect at all but the
      highest improvement rate. In patients with disc displacement with reduction,
      arthroscopy and disc repair/repositioning had statistically significant effects
      at all but the highest assumed rate of control group improvement. There were no
      statistically significant differences between the effects of any treatments.
      CONCLUSIONS: Surgical treatments appear to provide some benefit to patients
      refractory to nonsurgical therapies. The most reliable evidence supports the
      effectiveness of arthrocentesis and arthroscopy for patients with disc
      displacement without reduction. Better designed trials are needed before one can
      accurately determine the magnitude of the benefits of surgery.

PMID- 12524602
TI  - Ameloblastoma in young Jordanians: a review of the clinicopathologic features and
      treatment of 10 cases.
AB  - PURPOSE: We sought to descriptively review the clinicopathologic features and
      surgical treatment of ameloblastoma in children and young adults of Jordan.
      PATIENTS AND METHODS: Data were collected from the records of patients treated at
      the Oral and Maxillofacial Surgery Unit of Jordan University of Science and
      Technology between 1989 and 2002. RESULTS: Ten patients (4 males and 6 females)
      were included in the review. All of the cases involved the mandibular molar-ramus
      region. The most common presenting sign was that of a painless swelling. In 5 of
      the patients, a multilocular radiolucent radiographic appearance was seen; the
      remaining 5 cases had a large unilocular radiolucent appearance. While 2 tumors
      were devoid of microcystic regions, 2 exhibited only a few scattered cystic foci,
      and 6 were entirely cystic (unicystic). Cases with a unilocular radiographic
      appearance were treated by surgical enucleation plus rotary instrument peripheral
      ostectomy. Cases with a multilocular radiographic appearance were treated by
      surgical resection without a continuity defect. During the follow-up period
      (average of 7.6 years), no recurrence or metastasis was detected. All patients
      had desirable postoperative function and appearance. CONCLUSION: The
      clinicopathologic patterns of ameloblastoma in these young Jordanians were found
      to be similar to those of other whites. In this case series, minimal surgical
      treatment of mandibular ameloblastoma resulted in no recurrence and excellent
      postoperative function and appearance.

PMID- 12524603
TI  - Characterization of maxillofacial soft tissue vascular anomalies by ultrasound
      and color Doppler imaging: an adjuvant to computed tomography and magnetic
      resonance imaging.
AB  - PURPOSE: The special imaging and physical properties of ultrasound and color
      Doppler offer opportunity for continued investigation in oral and maxillofacial
      surgery. This study prospectively investigated ultrasound and color Doppler in
      addition to computed tomography (CT) and magnetic resonance imaging (MRI) in the
      characterization of several vascular or suspected vascular anomalies and assesses
      the value of ultrasound and color Doppler in their diagnoses. PATIENTS AND
      METHODS: Six patients with vascular or suspected vascular anomalies seen between
      1997 and 1999 composed the study group. All patients were clinically evaluated,
      imaged by CT with contrast and/or MRI with contrast, ultrasound, and Doppler
      (including color, spectral, and power). Ultrasound studies were performed in the
      presence of the referring oral and maxillofacial surgeons to provide consultation
      on anatomy and differential diagnosis as well as to witness the dynamic study.
      Three patients were further studied by angiography. The Mulliken/Glowacki
      classification (Plast Reconstr Surg 69:412, 1982) and designations and the
      Jackson et al modification (Plast Reconstr Surg 91:1216, 1993) are used in this
      study. RESULTS: A spectrum of lesions emerged in this small case series. Detailed
      clinical and imaging findings and a summary of diagnostic impressions allowed
      general and specific observations and permitted assessment of the value of
      ultrasound and color Doppler in the diagnosis of these lesions. The diagnostic
      accuracy of ultrasound and Doppler was equal to or better than that of CT and/or
      MRI in 4 of 6 cases. In the other 2 cases ultrasound did not specifically
      diagnose the lesions but did allow assessment of vascularity. In one of these
      cases the correct diagnosis was made by a combination of CT and angiography, and
      in the other the diagnosis was made by nonenhanced MRI. An ancillary study showed
      that the combination of nonenhanced MRI with ultrasound and Doppler provides more
      information than contrast-enhanced MRI alone and is more cost effective.
      CONCLUSIONS: 1) A single imaging modality is frequently unable to provide
      sufficient diagnostic information to allow confident clinical management of a
      vascular malformation. 2) A team approach and conferencing between imaging
      specialists and clinicians promote better diagnosis and management. 3)
      Nonenhanced MRI with ultrasound/color Doppler can be substituted for enhanced MRI
      to provide the best diagnostic information and at reduced cost. 4)
      Ultrasound/color Doppler is an important adjuvant to CT and MRI in the diagnosis
      of vascular or suspected vascular anomalies.

PMID- 12524604
TI  - Natural course of disc displacement with reduction of the temporomandibular
      joint: changes in clinical signs and symptoms.
AB  - PURPOSE: The goal of this study was to examine the natural course of disc
      displacement with reduction in the temporomandibular joint (TMJ). PATIENTS AND
      METHODS: This retrospective study involved 24 patients who had been diagnosed
      with disc displacement with reduction of the TMJ, but who had not undergone any
      treatment. The extent of maximal mouth opening, protrusion, lateral excursions,
      noise of the TMJ, pain of the TMJ, and tenderness of masticatory muscles were
      recorded monthly for a mean of 25.8 months. RESULTS: Maximal mouth opening,
      protrusion, and lateral excursions remained unchanged during follow-up. TMJ pain
      decreased by 15.7% (P >.05). Clicking decreased by 20.8% (P <.05), and tenderness
      of masticatory muscles decreased by 33.3% (P <.05). Reciprocal clicking remained
      unchanged in 19 patients (79.2%) and disappeared in 5 patients (23.8%). Four
      patients (16.7%) in whom clicking disappeared had a normal mouth opening, but
      locking developed in 1 patient (4.2%). CONCLUSIONS: In patients with disc
      displacement with reduction who do not undergo treatment, range of movement
      remains unchanged over time. Tenderness of masticatory muscles tended lessen, but
      reciprocal clicking and TMJ pain tended to remain. Clicking did not progress to
      locking in most patients.

PMID- 12524605
TI  - Bone marrow edema of the mandibular condyle related to internal derangement,
      osteoarthrosis, and joint effusion.
AB  - PURPOSE: The purpose of this prospective study was to evaluate whether common
      magnetic resonance imaging (MRI) variables such as temporomandibular joint (TMJ)
      internal derangement, osteoarthrosis, and effusion may predict the diagnostic
      group of bone marrow edema of the mandibular condyle. MATERIALS AND METHODS: The
      relationship between bone marrow edema and TMJ disc displacement, osteoarthrosis,
      and effusion was analyzed in MRIs of 120 TMJs in 73 consecutive patients with TMJ
      pain and/or a clinical diagnosis of TMJ internal derangement type III (disc
      displacement without reduction). The diagnostic bone marrow edema group was
      comprised of 54 TMJs in 40 patients with a unilateral or bilateral MRI diagnosis
      of bone marrow edema. The control group consisted of 66 non-bone marrow edema
      TMJs in 33 patients with a bilateral MRI finding of an absence of bone marrow
      edema. A logistic regression analysis was used to compute the odds ratios for
      internal derangement, osteoarthrosis, and effusion for non-bone marrow edema TMJs
      (n = 66) versus TMJs with bone marrow edema (n = 54). RESULTS: Using Chi;(2)
      analysis for pair-wise comparison, the TMJ-related data showed a significant
      relationship between the MR imaging findings of TMJ bone marrow edema and those
      of internal derangement (P = .000), osteoarthrosis (P = .000), and effusion (P =
      .010). Of the MRI variables considered simultaneously in the multiple logistic
      regression analysis, osteoarthrosis (P = .107) and effusion (P = .102) dropped
      out as nonsignificant in the diagnostic bone marrow edema group when compared
      with the control group. The odds ratio for individuals with an internal
      derangement showing bone marrow edema was strong (3.6:1) and highly significant
      (P = .000). Significant increases in risk of bone marrow edema occurred with disc
      displacement without reduction and osteoarthrosis (9.2:1) (P = .000) and disc
      displacement without reduction and effusion (6.4:1) (P = .002). CONCLUSIONS: The
      results suggest that the MR imaging findings for TMJ bone marrow edema are
      related to those of internal derangement, osteoarthrosis, and effusion. However,
      the data re-emphasize the aspect that internal derangement, osteoarthrosis, and
      effusion may not be regarded as the unique and dominant factors in defining TMJ
      bone marrow edema instances.

PMID- 12524606
TI  - Simple disc reshaping surgery for internal derangement of the temporomandibular
      joint: 5-year follow-up results.
AB  - PURPOSE: The goal of this study was to evaluate the clinical results of simple
      disc reshaping (SDR) surgery alone for treating dysfunctional internal
      derangement of the temporomandibular joint. PATIENTS AND METHODS: Eleven patients
      with symptomatic unilateral anterior disc displacement with disc deformation were
      treated using reshaping of the inferior surface of the disc without disc
      repositioning. This was performed as an open-joint procedure. All patients were
      evaluated clinically for joint pain and jaw motion 5 years after surgery.
      Structural changes of the joint tissues such as disc displacement and deformation
      were evaluated using magnetic resonance imaging. The postoperative results were
      compared with preoperative findings. RESULTS: Joint pain during mastication or
      opening was reported by all patients before surgery. In 10 of 11 patients (91%),
      the joint pain disappeared postoperatively. Preoperatively, all 11 patients had
      limitation of mouth opening: the mean opening was 24.9 mm (standard deviation
      [SD], 4.13 mm). Postoperatively, the mean opening increased to 43.0 mm (SD, 3.00
      mm). Based on the preoperative magnetic resonance imaging, all cases were
      diagnosed as anterior disc displacement without reduction and with disc
      deformation. Five years postoperatively, the disc configuration had maintained
      the reshaped status with decreased thickness of the deformed disc in 5 patients,
      and was changed to an almost normal biconcave shape in 3 patients. In the
      remaining 3 patients, the disc was unchanged from its preoperative condition. The
      position of the disc was unchanged in 8 patients, and in 3 patients disc position
      improved to near normal. CONCLUSION: The 5-year follow-up results suggest that
      SDR is a stable and favorable surgical procedure. Successful outcomes were
      attained in 91% of the patients.

PMID- 12524608
TI  - Follow-up of condylar fractures of the mandible in 8 patients at 18 months after
      transoral endoscopic-assisted open treatment.
AB  - PURPOSE: The results of endoscopic-assisted transoral approach for open reduction
      and miniplate fixation of condylar mandible fractures were evaluated 18 months
      after surgery. PATIENTS AND METHODS: The transoral endoscopic-assisted treatment
      of condylar fractures was performed in 8 consecutive patients from April 1998 to
      December 1999 at the University Hospital Freiburg. Four of 8 condylar fractures
      were dislocated, and 6 of the 8 patients had additional mandibular fractures.
      RESULTS: Anatomic reduction was achieved in all patients without facial nerve
      damage. There were no signs of bony resorption and good temporomandibular joint
      function 18 months after surgery. In 4 patients, the transoral management of
      condylar fractures was facilitated by angulated drills and screw drivers.
      Transbuccal stab incisions were not needed in these 4 patients. In all 8
      patients, visible scars were avoided. CONCLUSIONS: The endoscopic-assisted
      transoral approach proved to be a reliable surgical method for condylar fractures
      when dislocation with lateral override was present.

PMID- 12524609
TI  - Discectomy of the temporomandibular joint: 3-year follow-up as a predictor of the
      10-year outcome.
AB  - PURPOSE: The study goal was to evaluate whether the 3-year follow-up evaluation
      of temporomandibular joint (TMJ) discectomy in a consecutive series of patients
      with TMJ internal derangement was a reliable predictor for the 10-year outcome of
      the operation. MATERIAL AND METHODS: Twenty-nine patients with TMJ internal
      derangement were treated with discectomies, 6 bilaterally and 23 unilaterally.
      The patients were followed up for 10 years. RESULTS: The dropout rate was zero at
      the 3-year follow-up, and 5 patients (17.2%) had dropped out at the 10-year
      follow-up. There was a significant reduction in the median visual analog scale
      recordings, and all but 1 patient reported reduction in the pain score.
      Mandibular motion increased significantly after 3 years, and similar or improved
      recordings were made at the 10-year follow-up. All but 5 patients showed an
      increased motion at the 10-year follow-up compared with the preoperative motion.
      The only complication seen at the 10-year follow-up examination was a slight
      anesthesia of the auriculotemporal nerve in 1 patient. All types of additional
      therapy decreased significantly after the operations. CONCLUSIONS: Discectomy of
      the TMJ may significantly reduce pain and improve function in patients with
      internal derangement on a long-term basis. The 3-year follow-up examination
      proved to be a reliable predictor of the 10-year results.

PMID- 12524610
TI  - An assessment of maxillofacial fractures: a 5-year study of 237 patients.
AB  - PURPOSE: This descriptive analytical study assesses the cause, type, incidence,
      demographic, and treatment data of maxillofacial fractures managed at our medical
      center during a 5-year period and compares them with the existing body of
      literature on the subject. PATIENTS AND METHODS: A 5-year retrospective clinical
      and epidemiologic study evaluated 237 patients treated for maxillofacial
      fractures from 1996 to 2001 at one medical center. There were 211 male patients
      (89%) and 26 (11%) female patients. The patients ranged in age from 3 to 73
      years, with 59.0% (140 patients) in the 20- to 29-year age group. A number of
      parameters, including age, gender, cause of injury, site of injury, type of
      injury, treatment modalities, and complications, were evaluated. All
      maxillofacial injuries were assessed and treated by a single oral and
      maxillofacial surgeon. Other concomitant bodily injuries were treated by
      appropriate consultant specialists. RESULTS: There were 173 (72.9%) mandibular,
      33 (13.9%) maxillary, 32 (13.5%) zygomatic, 57 (24.0%) zygomatico-orbital, 5
      (2.1%) cranial, 5 (2.1%) nasal, and 4 (1.6%) frontal injuries. Car accidents
      caused 73 (30.8%), motorcycle accidents caused 55 (23.2%), altercations 23
      (9.7%), sports 15 (6.3%), and warfare caused 23 (9.7%) of the maxillofacial
      injuries. Regarding distribution of mandibular fractures, 32% were seen in the
      condylar region, 29.3% in the symphyseal-parasymphyseal region, 20% in the angle
      region, 12.5% in the body, 3.1% in the ramus, 1.9% in the dentoalveolar, and 1.2%
      in the coronoid region. The distribution of maxillary fractures was Le Fort II in
      18 (54.6%), Le Fort I in 8 (24.2%), Le Fort III in 4 (12.1%), and alveolar in 3
      (9.1%). Of the 173 mandibular fractures, 56.9% were treated by closed reduction,
      39.8% by open reduction, and 3.5% by observation only. Of 33 maxillary fractures,
      54.6% were treated using closed reduction, 40.9% using open reduction, and 4.5%
      with observation only. Approximately 52.1% of the patients were treated under
      general anesthesia, and 47.9% were treated under local anesthesia and sedation.
      Postsurgical complications were recorded in 5% of patients. These complications
      included infection, asymmetry, and malocclusion. Overall mortality in this series
      was 0.84% (2 patients); mortality was caused by pulmonary infection. CONCLUSION:
      The findings of this study, compared with similar studies reported in the
      literature, support the view that the causes and incidence of maxillofacial
      injuries vary from 1 country to another.

PMID- 12524612
TI  - The clinical anatomy of the maxillary artery in the pterygopalatine fossa.
AB  - PURPOSE: The purposes of this study were to delineate the maxillary artery and
      its branching arteries and to develop a classification of the various branching
      patterns by means of serial cadaver dissections of the pterygopalatine fossa
      region. MATERIALS AND METHODS: Fifteen Korean adult cadavers were used; 2 sides
      of each cadaver were examined, for a total of 30 sides. Before dissection of the
      pterygopalatine region, computed tomography scan was taken of 20 cadaver heads.
      Sectioned specimens of 9 sides of the cadaver heads in 3.0-mm thickness were made
      for this study. Then we dissected 21 sides of fresh cadavers under the
      microscope. In this investigation, we observed branching patterns of the third
      portion of the maxillary artery, a relationship of the terminal branches of the
      maxillary artery to the pterygomaxillary junction, and the course of descending
      palatine artery. Then we classified the branching patterns of the maxillary
      artery in the pterygopalatine fossa. RESULTS: From the pterygomaxillary junction
      to the pterygopalatine fossa region, the maxillary artery was usually branched
      into 5 arteries in the following order: posterior superior alveolar artery,
      infraorbital artery, artery of the pterygoid canal, descending palatine artery,
      and sphenopalatine artery. Of 21 cadavers, 18 showed this order (85.7%). There
      were 2 types of branching patterns of the posterior superior alveolar artery and
      the infraorbital artery. The average distance from the most inferior point of the
      pterygomaxillary junction to the posterosuperior alveolar artery, infraorbital
      artery, and descending palatine artery was 15.2, 32.2, and 24.8 mm, respectively.
      In most cases (95.2%), the greater and lesser palatine arteries were divided from
      the short descending palatine artery. According to the contours of the third
      portion of the maxillary artery, we classified them into 5 types: the "Y" type
      (19%), "intermediate" type (33.3%), "T" type (23.8%), and "M" type (14.3%).
      CONCLUSION: The results of this investigation show the common patterns of the
      maxillary artery.

PMID- 12524611
TI  - Evaluation of long-term stability in second metatarsal reconstruction of the
      temporomandibular joint.
AB  - PURPOSE: Our goal was to evaluate long-term stability and function of 5 condyles
      reconstructed with vascularized second metatarsal joint grafts. MATERIALS AND
      METHODS: Four patients were reconstructed with 5 vascularized metatarsal grafts.
      These reconstructed joints were then followed for an average of 12.5 years. These
      patients represent the entire series and were all successfully contacted and
      reevaluated for this article. Measures of opening, deviation, excursion,
      symmetry, and clinical symptoms relating to the reconstructed joints are
      evaluated. RESULTS: Mean preoperative interincisal aperture was 12 mm, and
      postoperative aperture 48.5 mm. Three unilaterally treated patients had lateral
      excursion with opening. The mean deflection was 4.3 mm toward the operated side.
      Lateral and protrusive movements were limited in reconstructed joints, but up to
      3 mm of protrusion was shown at 12.5 years. Subjectively, all patients rated
      their function as acceptable and were able to occlude and masticate without
      difficulty. Symmetry at rest was improved by surgery. CONCLUSIONS: Vascularized
      metatarsal joints represent a potentially suitable long-term substitute for
      condylar reconstruction. This limited series shows the technical viability of the
      procedure. A larger series may be warranted to compare this promising technique
      with conventional methods of temporomandibular joint reconstruction.

PMID- 12524613
TI  - A biologic model for assessment of osseous strain patterns and plating systems in
      the human maxilla.
AB  - PURPOSE: This study was conducted to examine a biomechanical model and to help
      answer fundamental questions that relate to rigid plate fixation in the maxilla.
      Specifically, we sought to elucidate the principal strain patterns generated in
      the maxilla secondary to masticatory forces as well as the amount of permanent
      deformational changes incurred due to these loading forces. MATERIALS AND
      METHODS: Cadaveric heads with the mandible removed were defleshed and placed in a
      2-part testing rig to hold and position the skull for testing in a standard
      material testing system. Rosette strain gages were attached at predefined points
      on the skull, and an Instron machine was used to load the skull through the
      loading port on the tray. A Le Fort I osteotomy was then performed on the skull,
      and a Walter Lorenz Ultra-Micro plating system was applied by a surgeon to
      reconnect the upper jaw. A 2-mm gap was left at the line of the osteotomy, and a
      transducer was attached to measure closure of the gap. Again the skull was loaded
      with the Instron (Canton, MA) machine. RESULTS: The results indicate a linear
      relationship exists with both maximum (tensile) and minimum (compressive) strain
      patterns relative to incremental load placement on the intact maxilla. The strain
      patterns after the Le Fort I osteotomy and plating were different and less
      linear. The differential variable reluctance transducer data showed a low rate of
      closure or transient increase in the gap at low loads (0 to 15 kilopond [kp]
      range) and a steeper slope of closure during high loads (15 to 60 kp range). It
      is also evident that axial loading forces cause permanent deformation and failure
      of osseous plating systems predominantly through bending. CONCLUSIONS: This model
      provides a foundation of knowledge regarding biomechanical strains in the maxilla
      subjected to static compressive loads in the force range of mastication. In
      addition, it serves as a comparative reference to assess rigidity of various
      craniofacial plating systems and to validate proposed standardized synthetic
      models. With the advent of increasingly precise surgery and new plating systems,
      this model can be used to help guide placement and design of plating systems;
      thereby allowing for ideal stabilization and optimizing surgical outcome.

PMID- 12524614
TI  - Computed tomography morphology of the mandibular ramus in prognathism: effect on
      the medial osteotomy of the sagittal split ramus osteotomy.
AB  - PURPOSE: The purpose of this study was to investigate the distribution of
      cancellous bone relative to performance of the medial osteotomy of a sagittal
      split ramus osteotomy using computed tomography scanning. PATIENTS AND METHODS:
      Skeletal Class III patients consisted of 11 males and 22 females with a mean age
      of 23 years. The control patients without dentofacial deformity consisted of 10
      males and 20 females with a mean age of 25 years. Scans were taken parallel to
      the mandibular occlusal plane, and morphologic measurements, including
      distribution of cancellous bone, were obtained. RESULTS: Compared with the
      control patients, the mandibular ramus of Class III patients was thinner with a
      more complicated and varied cancellous bone pattern, such as separate regions of
      cancellous bone and lack of cancellous bone posterior and anterior to the
      mandibular foramen. CONCLUSIONS: It was apparent that the safest region in which
      to establish the medial osteotomy line was just superior and 5 to 6 mm posterior
      to the lingula, directing the line slightly inferior.

PMID- 12524615
TI  - Formation of a mandibular condyle in vitro by tissue engineering.
AB  - PURPOSE: Mandibular reconstructive procedures often produce significant donor
      site morbidity. Recently, the use of minimally invasive techniques has been
      reported for mandibular reconstruction with decreased morbidity at the primary
      operative site. To date, these techniques have not addressed the graft donor
      site. We hypothesize that tissue-engineering techniques may be used to fabricate
      bone and thereby eliminate donor site morbidity. METHODS: Porcine mesenchymal
      stem cells (pMSCs) were isolated from the bone marrow of 3 Yucatan minipigs and
      grown in standard culture flasks. When they became near-confluent, cells were
      detached and replated with the addition of osteogenic supplements. A model of a
      porcine mandibular condyle was made and used to fabricate porous polymer
      scaffolds from biodegradable poly DL-lactic-co-glycolic acid (PLGA).
      Differentiated osteoblasts were transferred to the PLGA scaffold and cultured for
      6 weeks in a rotational oxygen-permeable bioreactor system. The cultured
      constructs, consisting of scaffold and cells, were evaluated by gross,
      radiologic, and histologic examinations. RESULTS: The engineered constructs were
      white and hard and had a shape that closely resembled that of the model condyle.
      Plain radiographs demonstrated that the radiodensity of the construct was between
      that of the normal condyle and that of control scaffolds. Histologically, bone
      was observed on the entire surface of the PLGA scaffolds with an average
      thickness of 0.03 mm. Bone was not observed in the control scaffolds. CONCLUSION:
      In this pilot study, autologous tissue-engineered bone constructs were
      successfully made by combining biodegradable polymers and pMSCs.

PMID- 12524617
TI  - Primary non-Hodgkin's lymphoma of the jaws: Report of 4 cases and review of the
      literature.

PMID- 12524616
TI  - Crosslinking of fibrinogen and fibronectin by free radicals: a possible initial
      step in adhesion formation in osteoarthritis of the temporomandibular joint.
AB  - PURPOSE: Adhesion formation in osteoarthritis (OA) of the temporomandibular joint
      (TMJ) typically results in a sustained limitation of joint movement. We propose
      the hypothesis that free-radical-mediated crosslinking of proteins underlies this
      adhesion formation in affected joints. Free radicals may cause oxidative
      modification of proteins, creating an opportunity for the formation of
      intramolecular and intermolecular crosslinks via covalent bonds. This may
      stabilize protein aggregates, rendering them more resistant to degradation. In
      this study, the free-radical-mediated crosslinking of model proteins (fibrinogen
      and fibronectin) was investigated to test our hypothesis that free radicals
      contribute to adhesion formation via this mechanism in OA of the TMJ. MATERIALS
      AND METHODS: Physiological clot formation of fibrinogen by thrombin and free
      radical-induced crosslinking of fibrinogen and of fibronectin were analyzed using
      spectrophotometric turbidity measurements, light-scattering techniques,
      polyacrylamide gel electrophoresis (PAGE), and rotary shadowing. RESULTS:
      Fibrinogen was shown to aggregate after free radical treatment, as detected using
      turbidity measurements and light-scattering techniques. Using PAGE, fibrinogen as
      well as fibronectin was shown to degrade under low oxidative stress. Under high
      oxidative stress, however, fragments from both proteins were found to be
      covalently crosslinked, resulting in high-molecular-weight protein aggregates.
      The aggregation was shown to be at random with rotary shadowing. CONCLUSION: The
      study shows that high oxidative stress contributes to the formation of
      crosslinked proteins that may serve as an initial scaffolding for the development
      of adhesions frequently seen in OA of the TMJ.

PMID- 12524618
TI  - Diagnostic confirmation of Langerhans cell histiocytosis of the jaws with CD1a
      immunostaining: a case report.

PMID- 12524619
TI  - Hypoesthesia in the inferior alveolar nerve as the unique clinical manifestation
      of Rosai-Dorfman disease.

PMID- 12524620
TI  - Intraoral salivary duct carcinoma: a report of 5 cases.

PMID- 12524621
TI  - Condylar osteochondroma with complete hearing loss: report of a case.

PMID- 12524622
TI  - Osteochondroma of the glenoid fossa: occurrence in an atypical location.

PMID- 12524623
TI  - Surgical ciliated cyst after maxillary orthognathic surgery: report of a case.

PMID- 12524624
TI  - Schwannoma of the vagus nerve first diagnosed as a parotid tumor.

PMID- 12524625
TI  - Subperiosteal endoscopic cranial augmentation (SECA): endoscopic approach to
      cranioplasty.

PMID- 12524626
TI  - Dentigerous cyst versus paradental cyst versus eruption pocket cyst.

PMID- 12524627
TI  - Third molar pathology: is submitted tissue a confounding variable?

PMID- 12524629
TI  - Depression in Kraepelinian schizophrenia.
AB  - In order to improve our understanding of depression in chronic schizophrenia,
      depressive symptoms were assessed in institutionalized, so called Kraepelinian,
      patients with schizophrenia (N = 43). The patients had been ill and dependent on
      others for at least 5 years. Depressive symptoms as measured by the Hamilton
      Depression (HAM-D) scale were less prevalent in this population compared to
      published data on non-Kraepelinian patients. Only 5% of our Kraepelinian patients
      had a HAM-D score >/= 16. There was also a low prevalence of core depressive
      symptoms (depressed mood, suicidal ideation, and guilt). The relationship of
      depression to other dimensions of schizophrenia was explored. Depression had a
      modest positive correlation (r = 0.44) with general psychopathology as measured
      by the Brief Psychiatric Rating Scale (BPRS), but not with positive symptoms as
      measured by BPRS positive subscale or negative symptoms as measured by the Scale
      for the Assessment of Negative Symptoms (SANS). Depression also showed a modest
      positive correlation (r =.48) using the Simpson-Angus Rating Scale (SAS) for
      extrapyramidal symptoms (EPS). These results indicate that in Kraepelinian
      schizophrenia, depression is not prevalent, even though patients are severely ill
      both in symptom and functioning domains. The results of our analysis support that
      Kraepelinian schizophrenia is a distinct subtype, and raise questions regarding
      the boundary between schizoaffective disorder and non-Kraepelinian schizophrenia.
      Finally, the low rate of depression observed revives the notion that preservation
      of core functional abilities is important for a depressive reaction to evolve in
      schizophrenia.

PMID- 12524630
TI  - The etiology of schizophrenia and the origin of language: overview of a theory.
AB  - Schizophrenia is present in all human populations with approximately the same
      incidence. Why does such illness persist given that it is associated with a
      reproductive disadvantage? What is the balancing advantage? A possible
      explanation is linked to human language. According to this hypothesis
      schizophrenia occurs as a manifestation of genetic diversity associated with
      language--the function by which Homo sapiens has separated from other primate
      species. Language originated by a genetic mutation that allowed the cerebral
      hemispheres to develop with a degree of specialization (or lateralization)
      reflected in cerebral asymmetries. Individuals with schizophrenia show lesser
      structural and functional brain asymmetries than the population as a whole, and
      this finding can be interpreted as a delay, or failure in, establishing
      hemispheric dominance for language. We review recent evidence supporting this
      theory.

PMID- 12524632
TI  - Bipolar II depressive mixed state: finding a useful definition.
AB  - Recent studies showed that depressive mixed state (DMX) (major depressive episode
      [MDE] with few hypomanic symptoms) was common among depressed outpatients. The
      aim of the present study was to find a clinicallly useful definition of DMX. A
      useful definition could be one increasing the probability of making the correct
      diagnosis of bipolar II. Different definitions of DMX were tested by comparing
      the sensitivity, specificity, and predictive power for the diagnosis of bipolar
      II. Three hundred thirty-six consecutive bipolar II (n = 206) and unipolar (n =
      130) MDE outpatients were interviewed with the DSM-IV Structured Clinical
      Interview-Clinician Version (SCID-CV). Different DMX definitions were tested,
      based on factor analysis, multivariate regression, discriminant analysis, and
      logistic regression analysis results. The sensitivity, specificity, correctly
      classified, and receiver operating characteristic (ROC) area for bipolar II
      diagnosis were compared. Two factors (factor 1, including irritability,
      psychomotor agitation, and more talkativeness, and factor 2, including racing
      thoughts, irritability, and distractibility) were significantly associated with
      bipolar II diagnosis. Of the hypomanic symptoms most common in bipolar II DMX,
      only irritability and racing thoughts were significantly associated with bipolar
      II diagnosis on discriminant analysis. DMX with three or more concurrent
      hypomanic symptoms (DMX3) was strongly associated with bipolar II diagnosis.
      Comparisons of sensitivity, specificity, correctly classified, and ROC area of
      the different DMX definitions (factor 1, factor 2, DMX3, irritability during MDE,
      racing thoughts during MDE) for the diagnosis of bipolar II, showed that factor 1
      had the best combination of sensitivity and specificity, high correctly
      classified and ROC, but DMX3 has the highest specificity, and slightly lower
      correctly classified and ROC than factor 1. A DMX definition having the highest
      specificity (DMX3) for bipolar II diagnosis may be more useful to clinicians,
      leading to few false positives. Bipolar II diagnosis has important treatment and
      clinical implications, but misdiagnosis is common because diagnosis is often
      based on history of hypomania (dependent on memory and clinical skills). A cross
      sectional marker like DMX3 may increase the probability of making the correct
      diagnosis of bipolar II, and therefore may be a useful definition of DMX.

PMID- 12524631
TI  - Characteristics of first suicide attempts in single versus multiple suicide
      attempters with bipolar disorder.
AB  - Although suicidality remains highly prevalent among patients with bipolar
      disorder, little research exists examining the characteristics of successive
      attempts among individuals who make and survive a first suicide attempt. We
      compared bipolar subjects with a history of one suicide attempt to those with
      multiple attempts and assessed demographic characteristics, family histories,
      psychopathology, and clinical dimensions of suicidal behavior. Fifty-two DSM-IV
      bipolar patients (age 21 to 74 years) with a history of at least one suicide
      attempt were consecutively evaluated in the Bipolar Disorders Research Clinic of
      the New York Presbyterian Hospital. Circumstances surrounding each lifetime
      suicide attempt were assessed by direct interviews, questionnaires, and chart
      reviews along with family psychiatric histories, substance abuse histories,
      current psychopathology, and features of impulsivity and aggression. Multiple
      suicide attempts occurred in approximately two thirds of the study group. Single
      attempters were significantly more likely than multiple attempters to show high
      seriousness of intent at their first attempt (OR = 0.65, 95% CI = 0.43 to 0.99),
      and tended to be less likely than multiple attempters to exhibit mixed states at
      their first attempt (OR = 0.54, 95% CI = 0.28 to 1.01). Seriousness of intent was
      consistent across the first and second attempts (r =.48, P <.01) and second and
      third attempts (r =.74, P <.05). Single and multiple attempters differed in no
      other clinical or demographic characteristics studied. We conclude that multiple
      suicide attempts are common among bipolar patients. Those who survive an initial
      suicide attempt involving high seriousness of intent appear less likely than
      those with low intent to make subsequent attempts. Consequently, single
      attempters may represent a group more closely resembling those who complete
      suicide on a first attempt, in terms of the risk for death associated with their
      first attempt. However, multiple suicide attempts among bipolar patients are not
      necessarily associated with a higher risk for lethality in first suicide attempt
      survivors.

PMID- 12524633
TI  - Frequency of comorbid personality disorders in bipolar and unipolar affective
      disorders.
AB  - One expression of the complex relationship between personality and affective
      disorder is the comorbidity of personality disorders (PDs) with affective
      disorders. In a sample of 117 patients with unipolar and 60 with bipolar
      affective disorders, we assessed DSM-III-R PDs with the Structured Clinical
      Interview for DSM-IV Personality Disorders (SCID-II) and compared them with
      personality factors as obtained by the five-factor model (FFM-NEO Five-Factor
      Inventory). Fifty-one percent of the unipolar and 38% of the bipolar disorders
      fulfilled criteria for a comorbid PD. The three most frequent PDs were obsessive
      compulsive PD, borderline PD, and narcissistic (bipolar) or avoidant (unipolar)
      PD. Cluster C PDs and especially avoidant PD occurred significantly more
      frequently in unipolar than in bipolar patients, while narcissistic PD occurred
      significantly more often in bipolar than in unipolar patients. The FFM results
      supported the validity of our PD diagnoses. In a logistic regression analysis,
      higher depression score at the time of the SCID-II interview and shorter duration
      of the illness were weakly related to a higher frequency of PDs. Our results
      indicate that PDs are frequent in affective disorders and that there are subtle
      differences between unipolar and bipolar patients concerning such comorbid
      disorders.

PMID- 12524634
TI  - Borderline personality disorder in major depression: symptomatology, temperament,
      character, differential drug response, and 6-month outcome.
AB  - Among 183 depressed patients participating in a randomized long-term treatment
      trial of fluoxetine and nortriptyline, 30 patients had borderline personality
      disorder (BPD), 53 had other personality disorders (OPD), and 100 had no
      personality disorders (NPD). The borderline depressed patients had earlier age of
      onset of their depressions, more chronic depressions, more alcohol and cannabis
      comorbidity, and were more likely to have histories of suicide attempts and of
      self-mutilation. On self-report, patients with BPD and OPD reported more phobic
      symptoms, greater interpersonal sensitivity, and more paranoid ideation.
      Uniquely, BPD patients were more angry than OPD patients. BPD patients had high
      novelty seeking, high harm avoidance, low self-directedness, and low
      cooperativeness. Depressed patients with BPD did poorly in the short term if
      treated with nortriptyline rather than fluoxetine. After 6 months, those with BPD
      had a favorable outcome in regard to depressive symptoms, social adjustment, and
      even improvement in the character measure of self-directedness. Those with the
      poorest outcome were those with OPD.

PMID- 12524635
TI  - Functioning and interpersonal relationships as predictors of response in
      treatment-resistant depression.
AB  - The purpose of this study was to examine whether occupational functioning or the
      quality of interpersonal relationships is predictive of clinical response to a 6
      week open trial of nortriptyline (NT) in patients with treatment-resistant
      depression (TRD). Ninety-two subjects with TRD were treated openly with NT for 6
      weeks. The longitudinal interval follow-up evaluation (LIFE) scale was
      administered at baseline. A logistic regression was performed using occupational
      functioning and interpersonal relationships (over the past month and over the
      past 5 years) as predictors of treatment response. Unpaired t tests were
      performed to examine mean composite LIFE score values between responders and
      nonresponders. The composite scores that were statistically significant were used
      as single predictors of treatment status in separate logistic regression
      equations. Better occupational function over the past 5 years predicted better
      response to treatment with NT in patients with TRD. Beyond a history of
      nonresponse to antidepressants, long-term occupational function may be a
      predictor of outcome in the treatment of TRD.

PMID- 12524637
TI  - The prevalence and clinical features of body dysmorphic disorder in college
      students: a study in a Turkish sample.
AB  - Body dysmorphic disorder (BDD) consists of a preoccupation with an imagined or
      slight defect in appearance, which causes significant distress or impairment in
      functioning. There has been little previous research about the prevalence and
      clinical features of BDD in different cultures. This study aimed to find the rate
      and the clinical features of BDD among 420 female college students in Turkey. A
      self-report questionnaire was used to determine the subjects' body
      dissatisfactions and compulsive behaviors. BDD was diagnosed using DSM-IV
      criteria. In this study, 43.8% of the subjects were dissatisfied with their
      appearance and 4.8% of all subjects were diagnosed with BDD. Head/face area and
      hips were the most common areas of concern. The results of this study suggested
      that body dissatisfaction and BDD among Turkish college students are not rare.

PMID- 12524636
TI  - Western personality models applied in Eastern Europe: Yugoslav data.
AB  - In this study, two leading "Western" models of personality developed in the
      United States are tested in Eastern Europe, specifically in Yugoslavia. First,
      the models were tested psychometrically, for their construct validity and cross
      cultural applicability. Next, these Western personality models were used to
      explore the underlying structure of axis II syndromes of personality disorder as
      observed in Yugoslav patients. Finally, the models were tested regarding their
      ability to diagnose and discriminate categorical diagnoses of axis I mental
      disorders (e.g., depression, anxiety, and psychoses). The Five Factor Model of
      personality and the Seven Factor Model of temperament and character were applied
      to normal subjects and clinical patients with categorical axis I and axis II
      diagnoses (depression, anxiety, psychosis, and personality disorder), at the
      Institute for Psychiatry, University of Belgrade, Yugoslavia. The sample included
      120 subjects: 90 hospitalized psychiatric patients and 30 normal subjects. The
      patients were females, from 20 to 45 years of age, classified into three groups:
      30 with depression, 30 with various anxiety syndromes, and 30 with psychosis
      (primarily patients with schizophrenia, paranoid type in remission). The results
      indicated solid psychometric validity of the two Western personality models in
      the ethnically and culturally different setting of Yugoslavia. Important
      diagnostic and structural relationships between dimensions of personality and
      axis I and II categorical diagnoses were observed. As expected, certain
      combinations of personality traits allowed for diagnosis, description, and
      discrimination of personality disorder subtypes. As a novel finding, personality
      traits discriminated anxious, depressive and psychotic axis I disorders.

PMID- 12524638
TI  - Dissociative symptoms and amnesia in Dutch concentration camp survivors.
AB  - We examined to what extent dissociative phenomena in concentration camp survivors
      are related to post-traumatic stress symptoms. Self-reports of amnesia for
      traumatic war events and other dissociative experiences were studied in a sample
      of 31 Dutch survivors of World War II (WWII) Japanese concentration camps.
      Seventeen survivors treated for war-related psychiatric symptoms were compared to
      14 concentration camp survivors who had no psychiatric diagnosis. Although
      survivors who received treatment scored significantly higher on the Impact of
      Event Scale and the Post-Traumatic Symptom Scale than control survivors, the two
      groups did not differ in terms of accessibility of war memories or dissociative
      experiences. Levels of post-traumatic stress symptoms were not significantly
      correlated with dissociative experiences. In both groups, reports of psychogenic
      amnesia for traumatic events were rare. Our results support previous studies
      demonstrating that post-traumatic stress symptoms are not necessarily accompanied
      by dissociative experiences. They also contradict the suggestion that amnesia is
      a common phenomenon in people who have been exposed to war atrocities.

PMID- 12524639
TI  - Bulimic family dynamics: role of parents' personality--a controlled study with
      the Temperament and Character Inventory.
AB  - The numbers of studies on the familial environment and personality of bulimic
      women have increased in recent years and results have revealed interesting
      features. In this study, we evaluated the temperament and character traits of
      patients with bulimia nervosa (BN) and their mothers and fathers, and we analyzed
      the correlation of temperament and character traits among members of these
      bulimic families. Finally, we tested the ability of the Temperament and Character
      Inventory (TCI) to discriminate between normal controls and bulimic subjects,
      their parents, and their families. Using the TCI, temperament and character
      features of 28 bulimic patients and their parents (23 fathers and 28 mothers)
      were analyzed and then compared with a control group of 29 women and their 27
      fathers and 29 mothers. Data suggest that both temperament and character factors
      are involved in BN. Bulimic individuals were high in harm avoidance and low in
      self-directedness. Their mothers were distinguished by low self-directedness. The
      fathers were low in persistence. Harm avoidance of bulimic women positively
      correlated with harm avoidance and negatively with self-directedness of their
      mothers. The bulimic family had low self-directedness as a common denominator
      observed in all family members. The observation that both temperament and
      character have important roles in the etiopathogenesis of bulimia nervosa has
      important treatment ramifications. The TCI was useful in discriminating between
      normal controls and bulimic subjects, their parents, and the whole family.

PMID- 12524640
TI  - The validation study and application of stratum-specific likelihood ratios in the
      Chinese version of SPAN.
AB  - The Davidson Trauma Scale (DTS) is a validated self-rating scale used in the
      diagnosis of post-traumatic stress disorder (PTSD). A shorter version of the DTS
      was developed to serve as a diagnostic screening tool. A four-item scale, the
      SPAN (named for its principal four items: Startle, Physiological arousal, Anger,
      and Numbness), was then developed. This report investigates the psychometric
      validation of the Chinese version of the SPAN (SPAN-C). Subjects were drawn from
      a sample of 210 survivors of the September 21, 1999 Chi-Chi Earthquake. The scale
      showed good internal consistency (Cronbach's alpha= 0.77) and test-retest
      reliability (r = 0.90). Concurrent validity was obtained against the clinical
      diagnostic interview, with a diagnostic accuracy of 0.8 at a SPAN-C score of 5.
      The recommended stratum-specific likelihood ratios were 0.04 (95% confidence
      interval [CI], 0.02 to 0.07) for the score range of 0 to 2, 0.93 (95% CI, 0.51 to
      1.71) for the score range of 3 to 4, 2.31 (95% CI, 1.17 to 4.57) for the score
      range of 5 to 6, and 5.23 (95% CI, 3.12 to 8.78) for scores above 7. The
      psychometric strength of the SPAN-C indicates its reliability for future use,
      particularly for screening for subjects with a possible diagnosis of PTSD.

PMID- 12524642
TI  - Chemoembolization of hepatocellular carcinoma--what to tell the skeptics: review
      and meta-analysis.
AB  - Transcatheter arterial chemoembolization (TACE) has become the standard treatment
      for patients with unresectable hepatocellular carcinoma (HCC). When untreated,
      patients with inoperable HCC have a median survival of three months. Given the
      widespread use of chemoembolization, accurate evidence of the impact of TACE on
      patient survival is critical. Several review articles have examined randomized
      controlled trials (RCTs) of TACE; however, these analyses are inherently flawed
      by including trials in which control groups were treated. There have been only
      four RCTs comparing TACE to untreated controls to date. None has demonstrated a
      significant impact of TACE on patient survival. However, in addition to severe
      methodological flaws, these RCTs were limited by low patient enrollment,
      precluding any meaningful conclusions. In contrast, several non-randomized trials
      have clearly demonstrated a significant benefit of TACE on patient survival. New
      RCTs examining the impact of chemoembolization on survival are urgently needed to
      provide definitive evidence for the increasing number of patients treated with
      TACE. A new, well-designed RCT would provide significant insight on the impact of
      chemoembolization on patient survival.

PMID- 12524643
TI  - Treatment of hepatocellular carcinoma with sub-selective transcatheter arterial
      oily chemoinfusion.
AB  - Transarterial therapy for primary liver cancer is gaining more acceptance. The
      technique of transarterial treatment of such cancers is, however, quite varied.
      To determine the value of our approach, we analyzed our experience with
      transarterial oily chemoinfusion (TOCI) of primary liver cancer over a 4.9-year
      period. Since 1997, over 300 such procedures have been performed at our
      institution. We report the results of the first 253 procedures, which were
      performed using a subsegmental technique with a mixture of doxorubicin,
      cisplatin, ethiodol, with selective Gelfoam embolization. Actuarial survival
      rates at 1, 2, and 3 years were calculated with Kaplan-Meier and multivariate
      analysis was performed by Cox regression. The median overall survival was 28.6 +/
      4.5 months following diagnosis. By univariate analysis, TNM clinical stage I or
      II, Karnofsky score above 80%, absence of extrahepatic disease, absence of
      vascular invasion, unifocal disease, pretreatment alpha-fetoprotein levels less
      than 500 ng/ml, hypervascularity of lesions, and lesion size less than 5 cm were
      all strong predictors of favorable patient survival at 1, 2, and 3 years (75%,
      60%, and 50% respectively). Based on our experience, TOCI with selective
      embolization has similar survival benefit as the traditional chemoembolization
      but is associated with fewer complications.

PMID- 12524644
TI  - Chemoembolization for hepatic metastases.
AB  - Liver metastases are one of the most difficult therapeutic challenges in modern
      oncologic practice. Few systemic therapies are effective for solid tumors in the
      liver. Resection is possible in a minority of patients and usually not curative.
      Image-guided therapies such as chemoembolization offer substantial
      intensification of treatment by combining tumor ischemia, increased drug
      concentrations, prolonged dwell time, and reduced systemic toxicity. Although not
      a curative therapy, durable responses are seen in most adenocarcinomas, which may
      contribute to prolongation and preservation of quality of life by delaying liver
      failure in patients with liver-dominant disease.

PMID- 12524645
TI  - Radiofrequency ablation of hepatic tumors.
AB  - Radiofrequency thermal ablation is receiving increasing attention as an
      alternative to standard surgical therapies for the treatment of liver neoplasms.
      Benefits over surgical resection include the anticipated reduction in morbidity
      and mortality, low cost, suitability for real time image guidance, the ability to
      perform ablative procedures on outpatients, and the potential application in a
      wider spectrum of patients, including nonsurgical candidates. This review
      examines reported clinical results of this new therapeutic technique, potential
      complications, current limitations, thermal ablation mechanisms, as well as
      technical features and diagnostic modalities used in the procedure.

PMID- 12524647
TI  - Diagnosis of hepatic neoplasms using CT arterial portography and CT hepatic
      arteriography.
AB  - Both computed tomography arterial portography (CTAP) and CT hepatic arteriography
      (CTHA) are CT techniques with angiographic assistance. The detection sensitivity
      of these techniques is high because marked lesion contrast can be obtained using
      direct delivery of contrast materials to the liver parenchyma or the tumors. The
      use of CTAP and CTHA may improve therapeutic results after transarterial
      embolization therapy for hepatocellular carcinomas because of their high
      diagnostic accuracy. Findings on CTAP or CTHA can sometimes help characterize the
      hepatic focal lesions. Thus, CTAP and CTHA are frequently performed as
      pretreatment examinations, although they are invasive compared to intravenous
      (IV) contrast-enhanced CT or magnetic resonance imaging. However, there are some
      potential pitfalls, such as nontumorous perfusion abnormalities. CTAP and CTHA
      are less effective for evaluation of patients with cirrhosis and portal
      hypertension. This article presents a current overview of CTAP and CTHA technique
      for diagnosis of hepatic neoplasms.

PMID- 12524646
TI  - Radiofrequency ablation beyond the liver.
AB  - Radiofrequency ablation (RFA) has begun to show promise for extrahepatic
      indications. Although much of the reported work on image-guided RFA of liver
      neoplasms is quite promising, it is even earlier in the evaluation and validation
      process for extrahepatic RFA, with few short-term and no long-term studies
      reported. Although there are much more data for liver RFA with almost 3,000 cases
      reported in the literature, there are a number of ongoing investigations of RFA
      for tumors in the kidney, lung, bone, breast, bone, and adrenal gland. Debulking
      and pain control with RFA present palliative options becoming increasingly
      popular weapons in the interventionalist's oncology arsenal. Metastatic disease
      with a wide variety of primary histologies in a myriad of locations may be
      treated with RFA after a careful consideration of the risk-to-benefit ratio
      balance. The RFA technique can be slightly different outside the liver.
      Specifically, differing dielectric tissue characteristics may markedly alter the
      RFA treatment. Each different RFA system has a unique risk and advantage profile.
      Extrahepatic indications and contraindications will be suggested. Treatment tips
      and the unique complications and considerations will be introduced for some of
      the more common extrahepatic locations.

PMID- 12524648
TI  - Continuous arterial infusion strategies using implanted ports.
AB  - Surgically implanted ports have been used in continuous or repetitive intra
      arterial (IA) chemotherapeutic infusions for patients with multiple liver
      metastases from colorectal cancer. Recently, a percutaneous implantation
      procedure was developed, facilitating safe and less invasive IA infusions in the
      treatment of various disease conditions. This article focuses on the
      interventional techniques for percutaneous implantation of a vascular access
      device, consisting of an indwelling catheter and an implantable port, to perform
      IA infusions. Additionally, we describe details of the alteration of blood flow
      by coil-embolization that can be performed to obtain selective drug distribution
      to the target area and to avoid side effects caused by the administration of the
      chemotherapeutic agent into nontarget areas.

PMID- 12524649
TI  - Developments in medical oncology and their implications for interventional
      radiology.
AB  - Although surgery and radiation therapy have always been spatially targeted,
      chemotherapy as administered by oncologists has remained steadfastly committed to
      non-targeted systemic delivery. Decades of pharmaceutical research have yielded
      agents appropriate for intravenous use, but countless potentially efficacious
      agents have been discarded because of pharmacokinetic and toxicity profiles
      unsuitable for systemic delivery. With the emerging technology of biological
      agents comes a new series of challenges. These agents tend to be larger, less
      long-lived, and antigenic when compared with the agents of the past. Meanwhile,
      interventional radiologists have shown that targeted methods of delivery can have
      substantial impact on the efficacy and toxicity of agents. Laboratory scientists
      have developed new bullets; we interventional radiologists have developed new
      guns. It is time we take advantage of potential synergies.

PMID- 12524650
TI  - Positron emission tomography in lung cancer.
AB  - Carcinoma of the lung is one of the most frequent malignancies and a major cause
      of mortality. The use of positron emission tomography (PET) has been extensively
      investigated in patients with carcinoma of the lung and has established clinical
      utility and cost-effectiveness in characterization of solitary pulmonary nodules
      and preoperative staging of carcinoma of the lung. Evolving applications in
      carcinoma of the lung include detection of recurrence, assessment of treatment
      response, radiotherapy planning, and prognosis. In addition, there is developing
      interest in combined anatomic/metabolic imaging and new tracer techniques, in
      particular gene expression imaging. This review aims to present existing data
      supporting the use of PET in carcinoma of the lung and to explore the evolving
      indications and future prospects of PET and lung cancer.

PMID- 12524651
TI  - 18F-fluorodeoxyglucose positron emission tomography in small-cell lung cancer.
AB  - Positron emission tomography (PET) imaging is not used routinely in small-cell
      lung cancer (SCLC) but has been proven useful in non-small-cell lung cancer. The
      performance of (18)F-fluorodeoxyglucose (FDG)-PET in patients with SCLC was
      evaluated in this study. Fifteen patients with proven SCLC were evaluated (8 men
      and 7 women; mean age, 68 years; range, 50-81 years). Among the 15 patients with
      SCLC, 3 were newly diagnosed and 12 had received chemotherapy or radiation
      therapy before PET. Five patients underwent surgery (3 newly diagnosed and 2
      after therapy) after PET scan, and 14 received chemotherapy, radiation therapy,
      or both. The patient who was not treated with chemotherapy or radiation therapy
      underwent surgery only. All patients had computed tomographic (CT) scans before
      PET and had clinical follow-up for at least 2 months after PET. The patients
      received 3.4 to 4.15 mCi of (18)F-FDG intravenously after fasting for at least 4
      hours. Whole-body PET scans were acquired approximately 50 min after injection by
      using an ADAC Laboratories C-PET plus scanner. Among the 12 patients treated
      before PET, 2 were found with solitary pulmonary nodules positive on PET.
      Subsequent surgical resection and pathology showed 1 true positive and 1 false
      positive (postradiation pneumonitis). Six of these 12 patients had extrapulmonary
      metastases or large intense hilar or pulmonary uptake on PET, or both. Four of
      these 12 had no evidence of abnormal FDG uptake and were considered true
      negatives. The 3 patients with newly diagnosed SCLC were all true positives on
      PET, confirmed by surgery. One false negative on CT scan was attributed to
      postradiation fibrosis. These preliminary data suggest that whole-body FDG-PET
      can provide the basis for determining which treatment modality would be the most
      appropriate during the early stages of SCLC, when surgery is still an option, and
      it is a useful tool to assess the effect of treatment in patients with this
      disease. A more accurate assessment of SCLC will be possible if FDG-PET scan is
      combined with CT during the early evaluation of these patients.

PMID- 12524652
TI  - Peptide and antibody imaging in lung cancer.
AB  - Noninvasive differentiation of malignant from benign pulmonary nodules and the
      staging of lung cancer are major challenges and opportunities for radionuclide
      imaging. Despite the performance of (18)F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) imaging in addressing these needs, access to PET
      imaging in the United States and other countries is still limited for many
      people. Furthermore, FDG-PET imaging has left room for improvement. Thus, the
      need for addressing these diagnostic issues exists for a significant portion of
      the population of the United States and the rest of the world. Labeled antibody
      and peptide single-photon emission computed tomography imaging offers a
      reasonable alternative for these indications and comes close to FDG-PET imaging
      in performance, along with a lower cost when all overhead is included. Although
      these tracers have a high sensitivity in the diagnosis of primary and metastatic
      tumors, their specificity is limited by uptake in granulomatous disease, similar
      to that of FDG-PET. Regardless of these daunting challenges, radiolabeled
      antibody and peptide imaging deserves a recognized role in the clinical
      management of lung cancer.

PMID- 12524653
TI  - Positron emission tomography imaging in nonmalignant thoracic disorders.
AB  - The role of the fluorodeoxyglucose (FDG) technique positron emission tomography
      (PET) is well established in the management of patients with lung cancer.
      Increasingly, it is becoming evident that FDG-PET can be effectively employed to
      diagnose a variety of benign pulmonary disorders. Knowledge of such applications
      further expands the domain of this powerful modality and further improves the
      ability to differentiate benign from malignant diseases of the chest. We describe
      pertinent technical factors that substantially contribute to optimal imaging of
      the thoracic structures. Particularly, the complementary role of attenuation
      correction (AC) to that of non-AC images is emphasized. We further outline the
      need for and the state of the art for co-registration of PET and anatomic images
      for diagnostic and therapeutic purposes. We then review patterns of physiologic
      uptake of FDG in thoracic structures, including the lung, the heart, the aorta
      and large arteries, esophagus, thymus, trachea, thoracic muscles, bone marrow,
      and joints and alterations following radiation therapy to the thorax. A great
      deal of information is provided with regard to differentiating benign from
      malignant nodules and in particular, we emphasize the role of dual time point
      imaging and partial volume correction for accurate assessment of such lesions.
      Following a brief review of the diagnostic issues related to the assessment of
      mediastinal adenopathies, the role of FDG-PET imaging in environment-induced lung
      diseases, including pneumoconiosis, smoking, and asthma are described. A large
      body of information is provided about the role of this technology in the
      management of patients with suspected infection and inflammation of the lungs
      such as acquired immunodeficiency syndrome, fever of unknown origin, sarcoidosis,
      chronic granulomatous disease and monitoring the disease process and response to
      therapy. Finally, the value of FDG-PET in differentiating benign from malignant
      diseases of the pleura including asbestosis-related disorders is described at the
      conclusion of this comprehensive review.

PMID- 12524654
TI  - Disturbed regulation of cholesterol synthesis in monocytes of obese patients with
      hypercholesterolemia.
AB  - The aim of the present study was to clarify the influence of obesity on the
      functions of low-density lipoprotein receptors (LDL-R) and 3-hydroxy-3
      methylglutarate-coenyzme A (HMG-CoA) reductase both in healthy control subjects
      and in patients with hypercholesterolemia (HC). Experiments were performed on
      monocytes of 15 non-obese (C I) and 11 obese (C II) healthy control subjects and
      on 22 non-obese (HC I) and 26 obese (HC II) patients with HC. [(125)I]LDL was
      used to determine LDL-R activity by measuring binding and intracellular
      degradation. The rate of endogenous cholesterol synthesis was measured using
      [(14)C]acetate incorporation into the cholesterol fraction of monocytes. The
      binding ability of [(125)I]LDL was identical across all groups. The
      [(14)C]acetate incorporation in resting monocytes was increased only in obese HC
      group. The 50-microg/mL LDL protein-induced inhibition of [(14)C]acetate
      incorporation was significantly diminished (P <.001) in the same group. A strong
      positive correlation was detected between the [(14)C]acetate incorporation by
      resting cells and LDL-induced inhibition in all groups except the obese HC group,
      in which their correlation was negative (P <.001). Furthermore, in the obese HC
      group, a significant positive correlation was detected between body mass index
      (BMI) and the basal level of [(14)C]acetate incorporation, whereas a negative
      correlation was found between BMI and LDL-induced inhibition of [(14)C]acetate
      incorporation. The present data suggest that in patients with HC the concomitant
      obesity results in dysregulation of cholesterol homeostasis, which may contribute
      to the accelerated atherosclerosis.

PMID- 12524655
TI  - Antidiabetic actions of arachidonic acid and zinc in genetically diabetic Goto
      Kakizaki rats.
AB  - In previous studies, we showed that feeding arachidonic acid (AA) supplemented
      with a fixed amount of zinc lowered blood glucose concentrations in the fed state
      and water intake in rats with streptozotocin-induced diabetes. The present study
      was designed to determine dose-dependent effects of AA supplemented with a fixed
      amount of zinc on fed blood glucose levels, water intake, and glucose tolerance
      in genetically type 2 diabetic Goto-Kakizaki (G-K) Wistar rats. In an acute
      study, 20 mg/kg AA plus 10 mg/kg zinc administered via gastric gavage
      significantly improved oral glucose tolerance in G-K rats when compared to rats
      given distilled water (DW) only. When rats were treated chronically (2 weeks)
      with increasing doses of AA in drinking water, fed blood glucose concentrations
      and water intake were maximally decreased with diets containing 20 or 30 mg/L AA
      plus 10 mg/L zinc. Three-hour average area-above-fasting glucose concentrations
      (TAFGC; index of oral glucose tolerance) in diabetic G-K rats treated with 10,
      20, or 30 mg/L AA plus 10 mg/L zinc for 2 weeks were significantly decreased
      relative to DW-treated rats. The effect on TAFGC values was maintained for an
      additional 2 weeks after cessation of treatment. Plasma insulin levels
      significantly increased in rats treated with 20 mg/L AA only or 10 mg/L AA plus
      10 mg/L zinc, but not in rats treated with 20 or 30 mg/L AA plus 10 mg/L zinc,
      which are the most effective doses for the improvement of clinical signs of
      diabetes in G-K rats. In in vitro assays, 0.2 mg/mL AA in the incubation media
      was optimal for glucose uptake in isolated soleus muscle slices. These results
      suggest that treatment of genetically diabetic G-K rats with AA plus zinc lowers
      blood glucose levels via improvement of insulin sensitivity.

PMID- 12524656
TI  - Maternal protein restriction before pregnancy affects vital organs of offspring
      in Wistar rats.
AB  - Epidemiologic studies indicate that undernutrition during fetal growth can have
      long-term effects on adult health. However, it is not known whether these effects
      are also associated with maternal undernutrition before conception. The objective
      of the present study was to examine the effect of dietary restriction before
      pregnancy on the vital organs and blood parameters of offspring at different time
      points. Wistar female rats in the restricted group were fed a diet consisting of
      80 g protein/kg for 8 weeks before pregnancy and switched to 160 g protein/kg
      (control) from day 0 of pregnancy, while animals from the control group were fed
      160 g protein/kg throughout life. The progeny were studied at birth (n = 71), at
      94 days (n = 20), and at 180 days (n = 16). Weight gain during pregnancy was
      significantly lower (P <.01) for dams in the restricted group. At birth, relative
      weight for brain was lower (P </=.008), while for kidney it was higher (P
      </=.008) in the restricted group compared to control. At 94 days, the relative
      weights of brain, liver, and heart were lower (P </=.01 for all) in the
      restricted group than in the control group. However, at 180 days, only liver and
      kidney showed lower (P </=.01 for both) relative weights. Further, in the
      restricted group, increases in blood glucose at 94 days and in cholesterol at 180
      days were significant (P <.01 for both) in the offspring. The results thus
      indicate that maternal undernutrition before conception not only affected growth
      of vital organs, but also resulted in increased levels of glucose and cholesterol
      in the offspring at adulthood.

PMID- 12524657
TI  - Inhibitory effect of ceramide on insulin-induced protein kinase Czeta
      translocation in rat adipocytes.
AB  - Ceramide has been confirmed to be a signal mediator of apoptosis that is induced
      by tumor necrosis factor-alpha (TNF-alpha). It has also been reported that
      ceramide may induce insulin resistance as well as TNF-alpha. We investigated the
      effect of ceramide on insulin signaling pathways, such as insulin receptor (IR)
      beta-subunit, insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase
      (PI3K), and protein kinase Czeta (PKCzeta) in rat adipocytes. We examined insulin
      stimulated [(3)H]2-deoxyglucose (2-DOG) uptake in rat adipocytes pretreated with
      N-hexanoylsphingosine (C(6)-ceramide, 10 to 30 micromol/L). Insulin-induced 2-DOG
      uptake was significantly reduced by C(6)-ceramide pretreatment. We also examined
      the effect of various concentrations of C(6)-ceramide pretreatment on insulin
      induced autophosphorylation of the IR beta-subunit, tyrosine phosphorylation of
      IRS-1, enzyme activity of PI3K, and membrane-associated PKCzeta immunoreactivity.
      Pretreatment with C(6)-ceramide significantly reduced autophosphorylation of the
      IR beta-subunit, tyrosine phosphorylation of IRS-1, and enzyme activity of PI3K.
      Moreover, membrane-associated PKCzeta immunoreactivity and immunoprecipitable
      PKCzeta enzyme activity, downstream of PI3K, were significantly suppressed by
      C(6)-ceramide pretreatment. These results suggest that ceramide may induce
      insulin resistance via the suppression of IRS-1-PI3K signaling, and subsequent
      activation of PKCzeta.

PMID- 12524658
TI  - Glutamic acid decarboxylase and ICA512/IA-2 autoantibodies as disease markers and
      relationship to residual beta-cell function and glycemic control in young type 1
      diabetic patients.
AB  - Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid
      decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed
      as predictive markers of type 1 diabetes mellitus. To ascertain residual beta
      cell function and the clinical relevance for monitoring autoimmunity after
      clinical manifestation of disease, we studied 63 children at diagnosis of type 1
      diabetes (mean SD age 7.5 +/- 4 years) and 91 adolescent patients with type 1
      diabetes (age 14.7 +/- 1.6 years) with a mean duration of disease of 7 +/- 3.5)
      years. Forty-two normal adolescent subjects (age 14.6 +/- 1.8 years) without a
      family history of diabetes were the control group. Anti-GAD(65) and ICA512/IA-2
      Ab were assessed by a quantitative radioimmunoprecipitation assay. The
      relationship between humoral autoimmunity and clinical parameters was explored.
      GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed
      children and the prevalence was not different in relationship to clinical
      characteristics. Levels of GAD(65) Ab positively correlated with diagnosis age (P
      <.05). Both Ab were associated with islet cell antibodies (ICA) (P <.05), but one
      fifth of patients had at least 1 of the 2 Ab and absent ICA. At onset, only age
      showed a significant relationship to residual C-peptide secretion. Among the
      cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2
      Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed
      children, respectively) and more patients were identified by these Ab (68%) than
      by ICA alone (34%) (P <.05). In this cohort, levels of ICA512/IA-2 Ab negatively
      correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with
      daily insulin requirement (P <.05). Moreover, the presence of some residual C
      peptide secretion was significantly associated with the presence of ICA512/IA-2
      Ab (P <.05). Our findings confirm that positivity for either GAD(65) or ICA512/IA
      2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group,
      identifying a group of patients with absent ICA immunofluorescence. The
      persistence of Ab to islet tyrosine phosphatase possibly represents a marker of
      better glycemic control and less insulin requirement, indicating residual beta
      cell function, thus conferring clinical and prognostic relevance to these Ab, as
      well as potential usefulness in intervention strategies.

PMID- 12524659
TI  - Ethyl icosapentate (omega-3 fatty acid) causes accumulation of lipids in skeletal
      muscle but suppresses insulin resistance in OLETF rats. Otsuka Long-Evans
      Tokushima Fatty.
AB  - Ethyl icosapentate (EPA) is known to improve insulin resistance in non-insulin
      dependent diabetes mellitus (NIDDM); however, its mechanism is unclear. In this
      study, we attempted to determine the mechanism of EPA's effects on insulin
      resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Administration of
      EPA caused a reduction in plasma cholesterol and triglycerides, but increased
      cholesterol and triglyceride contents in skeletal muscle. EPA did not have an
      effect on glucose or insulin levels. EPA accelerated the glucose infusion rate
      (GIR) and improved the endothelium-dependent relaxation of OLETF rat the thoracic
      aorta caused by addition of acetylcholine. However, the improvement observed in
      endothelium-dependent relaxation disappeared after addition of N(w)-nitro-L
      arginine (L-NA). Furthermore, when L-NA and indomethacine were added to the
      medium, relaxation of the aorta in EPA-treated rats was weaker than that in
      control rats. These actions may cause NO induction in the endothelium and an
      increase in prostaglandin I(2) (PGI(2)) and prostaglandin I(3) (PGI(3)) action,
      which in turn may result in improvement of insulin resistance.

PMID- 12524661
TI  - Glycated high-density lipoprotein regulates reactive oxygen species and reactive
      nitrogen species in endothelial cells.
AB  - Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk
      of developing atherosclerosis in patients with diabetes mellitus. Although it is
      believed that high-density lipoprotein (HDL) is glycosylated at an increased
      level in diabetic individuals, little is known about a possible linkage between
      glycated HDL and endothelial dysfunction in diabetes. To clarify whether glucose
      modified HDL affects the function of endothelial cells, we first examined herein
      the level of H(2)O(2) generation from cultured human aortic endothelial cells
      (HAECs) exposed to a glycated oxidized HDL (gly-ox-HDL) prepared in vitro.
      Incubation for 48 hours with 100 microg/mL of gly-ox-HDL induced significant
      release of H(2)O(2) from cells and gly-ox-HDL-induced H(2)O(2) formation was
      inhibited in the presence of diphenyleneiodonium, an inhibitor of NADPH oxidase.
      In addition, stimulation of HAECs with gly-ox-HDL for 48 hours elicited a marked
      downregulation of catalase and Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD),
      suggesting H(2)O(2) formation by gly-ox-HDL to be due to a disturbance involving
      oxidant and antioxidant enzymes in the cells. Treatment of HAECs with gly-ox-HDL
      attenuated the expression of endothelial nitric oxide synthase (eNOS), but not
      inducible nitric oxide synthase (iNOS), and this was followed by decreased
      production of nitric oxide (NO) by the cells. Furthermore, in vitro experiments
      with glycated HDL (gly-HDL) in the presence of 2 mmol/L EDTA and Cu(2+)-oxidized
      HDL suggested the effect of gly-HDL on endothelial function to be possibly
      potentiated by additional oxidative modification. Taking all of the above
      findings together, gly-ox-HDL may lead to the deterioration of vascular function
      through altered production of reactive oxygen species and reactive nitrogen
      species in endothelial cells.

PMID- 12524660
TI  - Lack of pleiotropic genetic effects between adiposity and sex hormone-binding
      globulin concentrations before and after 20 weeks of exercise training: the
      HERITAGE family study.
AB  - The relationship between sex hormone-binding globulin (SHBG) concentrations and
      body fat accumulation and distribution is governed by complex dynamic factors,
      which may involve common genetic and/or environmental factors. The current study
      investigated the genetic and environmental basis for the correlation between SHBG
      and body fat. Several measures of adiposity were investigated including body mass
      index (BMI) and a trunk to extremity skinfold thickness ratio (TER) assessed by
      anthropometry, body composition measured by hydrostatic weighing (total body fat
      mass [FM], fat-free mass [FFM], and percent body fat [%BF]), and abdominal fat
      measured by computerized tomography scanning (abdominal visceral fat [AVF]). The
      study comprised 501 white subjects from 99 families and 277 black subjects from
      117 families participating in the HERITAGE Family Study. Familial correlations
      between traits and their cosegregation were investigated both at baseline and in
      response to endurance exercise training. Significant inverse phenotypic
      correlations were detected in both races between SHBG and adiposity measures at
      baseline and also in response to training. Significant cross-trait familial
      resemblance was found between SHBG and both BMI and FFM at baseline that
      accounted for 11% and 4% of maximal heritability, respectively, in white
      families. However, a joint segregation analysis of the traits failed to implicate
      shared genetic effects. Specifically, neither a pleiotropic major locus nor
      pleiotropic polygenic effects were detected between SHBG and BMI or FFM. A
      maximal cross-trait heritability of 45% was obtained for SHBG and TER at baseline
      in black families. However, no firm conclusions as to the etiology of this
      relationship could be drawn because of the limitations of small sample size. For
      the training response phenotypes, there was no significant cross-trait
      correlation between SHBG and any adiposity measures studied here, suggesting that
      their correlation may have an environmental basis. Therefore, this study fails to
      support the hypothesis of genetic pleiotropy between SHBG concentrations and body
      fat phenotypes, and suggests an environmental basis for the correlation, ie, SHBG
      concentrations are genetically independent of body composition and abdominal
      adiposity phenotypes.

PMID- 12524662
TI  - Effects of short- and long-term growth hormone replacement on lipoprotein
      composition and on very-low-density lipoprotein and low-density lipoprotein
      apolipoprotein B100 kinetics in growth hormone-deficient hypopituitary subjects.
AB  - In this study, we concurrently examined the effects of 8 and 40 weeks of growth
      hormone replacement (GHR) on lipids, lipoprotein composition, low-density
      lipoprotein (LDL) size, very-low-density lipoprotein (VLDL) apolipoprotein (apo)B
      kinetics and LDL apoB kinetics. Eight weeks of GHR did not alter lipid profiles.
      Forty weeks of GHR increased high-density lipoprotein-cholesterol (HDL-C)
      concentration (P =.01), nonsignificantly reduced LDL-C (P =.06), and reduced the
      HDL/LDL-C ratio (P =.04). Forty weeks of GHR increased HDL free cholesterol (P
      =.03), total cholesterol (P =.01), and cholesterol ester (P <.01) concentrations.
      No other significant changes in VLDL, LDL, or HDL composition or LDL size were
      noted at any time. Eight weeks of GHR reduced VLDL apoB absolute secretion rate
      (ASR, P =.03), with nonsignificant reductions in fractional secretion rate (FSR,
      P =.09) and pool size (P =.09). After 40 weeks of GHR, the VLDL apoB ASR, FSR,
      and pool size were not significantly different from baseline. Forty weeks of GHR
      increased both LDL apoB FSR (P =.02) and LDL apoB ASR (P =.04), with a small
      decrease in pool size. Thus, GHR may have important antiatherogenic effects; HDL
      C increased, LDL-C was nonsignificantly reduced, the total/HDL-C ratio was
      reduced, VLDL apoB production was reduced, and LDL apoB turnover was increased.

PMID- 12524663
TI  - Regulation of leptin release by insulin, glucocorticoids, G(i)-coupled receptor
      agonists, and pertussis toxin in adipocytes and adipose tissue explants from
      obese humans in primary culture.
AB  - The basal release of leptin by adipocytes from massively obese human subjects
      incubated for 48 hours in serum-free suspension culture was comparable to that by
      explants of subcutaneous adipose tissue from the same obese individuals. There
      was no stimulation due to dexamethasone or insulin alone of leptin release by
      adipocytes. However, the combination of insulin and dexamethasone doubled leptin
      release by adipocytes. The release of leptin was also stimulated by agonists of
      G(i)-coupled receptors (prostaglandin E(2) [PGE(2)], brimonidine [an alpha(2)
      catecholamine agonist] and cyclopentyladenosine [CPA]) in the presence of
      dexamethasone. Leptin release by these agents was further enhanced by insulin in
      both adipocytes and adipose tissue. Pertussis toxin, which irreversibly
      inactivates G(i) heterotrimers, inhibited leptin release and abolished the
      stimulatory effects of G(i)-coupled receptor agonists. However, pertussis toxin
      did not block the stimulation of leptin release by insulin in either adipose
      tissue or adipocytes. These data indicate that the release of leptin by human
      adipocytes cultured for 48 hours in a serum-free medium is comparable to that by
      explants of adipose tissue except that dexamethasone stimulation of leptin
      release requires the presence of insulin.

PMID- 12524664
TI  - Smokeless nicotine administration does not result in hypertension or a
      deterioration in glucose tolerance or insulin sensitivity in juvenile rats.
AB  - We have previously reported that smokeless nicotine resulted in hypertension, but
      not a deterioration in glucose tolerance or insulin action in young adult male
      rats. To evaluate the effect of nicotine in juvenile animals, we studied 6-week
      old male and female Sprague-Dawley rats and implanted 25-mg nicotine (N) or
      placebo (P) pellets. Weight gain was controlled by chow restriction in all 4
      groups of rats. Males were generally heavier than females, both before and after
      N or P placement; there was no difference in weight between N and P groups for
      each sex. Systolic blood pressure, measured noninvasively, increased modestly,
      but not significantly, after N placement in both male and female rats. Glucose
      tolerance and insulin action were assessed by an oral glucose tolerance test
      (OGTT). Areas under the curve (AUC) were calculated for glucose (AUC(GLU)),
      insulin (AUC(INS)), and free fatty acids (FFA) (AUC(FFA)). Insulin action was
      calculated by several indices, which have correlated with more invasive studies.
      None of these metabolic parameters were significantly impacted by nicotine
      treatment, consistent with our observations in adult male rats. In summary,
      smokeless nicotine at this dose has no significant effect on observed
      cardiovascular or metabolic parameters in sexually immature male and female rats.

PMID- 12524665
TI  - Impact of abdominal visceral fat, growth hormone, fitness, and insulin on lipids
      and lipoproteins in older adults.
AB  - We examined the relationship between abdominal visceral fat (AVF) and plasma
      concentrations of lipids and lipoproteins in 19 females (F) (not on estrogen) and
      31 males (M) over the age of 60 (age = 66.8 years). In addition, the effects of
      growth hormone (GH) release, fitness (Vo(2) peak), insulin, and glucose
      concentrations (both fasting and in response to an oral glucose tolerance test)
      on lipids were examined. Subjects were categorized by low (L) and high (H) AVF (L
      < 130 cm(2), H > 130 cm(2)), fat mass (FM) (above or below median value), and AVF
      corrected for fat mass. Factorial analysis of variance (ANOVA) showed that when
      subjects were divided by AVF and FM, similar results were observed with H > L (P
      <.05) for very-low-density lipoprotein-cholesterol (VLDL-C), triglycerides (TG),
      VLDL-TG, apolipoprotein (apo)-B, apo-B VLDL, cholesterol (Chol)/high-density
      lipoprotein (HDL), LDL/HDL, apoB/A1 and L > H for HDL, HDL(2), HDL(3), apo A1,
      and LDL/apo-B LDL. Gender differences were also observed with F > M for Chol,
      LDL, HDL, and HDL(2). When AVF was corrected for FM, these gender differences
      were still present. After correcting for FM, differences remained between H and L
      AVF groups for VLDL, TG, VLDL-TG, apo-B, apo-B LDL, apo-B VLDL, apoB/A1 (P <.05).
      Twenty-four hour integrated GH concentration (IGHC) was inversely related to
      VLDL, TG, VLDL TG, LDL TG, apoB, apoB VLDL, apoB LDL, Chol/HDL, LDL/HDL, and
      apoB/A1 in F, but not M (P <.05). Vo(2) peak was directly related to Chol, LDL,
      HDL(3), and apoB LDL with stronger relationships observed in F. Fasting insulin
      was related to lipids and lipoproteins in both men and women. These data suggest
      that, in older adults, elevated levels of AVF, FM, and AVF corrected for FM are
      associated with unfavorable lipid-lipoprotein profiles and extend similar
      findings reported in younger males and females with elevated AVF. These data also
      support previous findings indicating that AVF is a primary determinant of GH
      release.

PMID- 12524666
TI  - Enteroinsular axis of db/db mice and efficacy of dipeptidyl peptidase IV
      inhibition.
AB  - In type 2 diabetic patients, the administration of glucagon-like peptide-1 (GLP
      1), known as an incretin, exerts antidiabetic effects. However, GLP-1 is rapidly
      degraded by dipeptidyl peptidase IV (DPPIV) after its release. DPPIV inhibition
      is thought to be a rational strategy to treat type 2 diabetes. In this study,
      using C57BLKS/J-db/db (db/db) mice as a model of type 2 diabetes, we examined the
      effect of acute DPPIV inhibition on glucose tolerance at the early and later
      stages of diabetes, determining plasma active GLP-1 and insulin levels. In
      addition, we investigated changes of plasma DPPIV activity. Compared with normal
      C57BL6/J (B6) and db/+ mice, significantly increased plasma DPPIV activities were
      observed in db/db mice. Expression of the proglucagon gene encoding GLP-1 was
      significantly upregulated in the colon of db/db mice. The administration of
      valine-pyrrolidide, a DPPIV inhibitor, resulted in potentiated insulin secretion
      mediated by increased endogenous GLP-1 action, leading to improved glucose
      tolerance in db/db mice at 6 weeks of age. However, although acute DPPIV
      inhibition with valine-pyrrolidide resulted in higher plasma active GLP-1 and
      insulin levels in db/db mice at 23 weeks of age, it did not improve glucose
      tolerance. The function of the enteroinsular axis is preserved in both stage of
      diabetes and the DPPIV inhibitor potentiated it, but the progression of insulin
      resistance appeared to block the improvement of glucose tolerance through DPPIV
      inhibition. Our results suggest that DPPIV inhibition is a suitable approach for
      treatment of impaired glucose tolerance (IGT), and type 2 diabetes in the early
      stage.

PMID- 12524667
TI  - Neutrophil intracellular pH and Na+/H+ exchanger activity in pre-eclampsia.
AB  - Elevated Na(+)/H(+) exchanger activity and intracellular acidosis have previously
      been demonstrated in white blood cells isolated from women who have suffered from
      a pre-eclamptic pregnancy. The mechanisms underlying this abnormality and the
      implications in pre-eclamptic pregnancies are, at present, unclear. In this
      study, we used neutrophils from third trimester pre-eclamptic patients and third
      trimester normotensive pregnant controls to determine Na(+)/H(+) exchanger
      isoform-1 (NHE-1) activity and intracellular pH. This was performed using a well
      validated technique involving flurometry and a pH sensitive dye, 2,7'Bis
      (carboxyethyl) 5.6 carboxyfluorescein acetomethyl ester (BCECF-AM). Time course
      experiments were performed to assess the contribution of plasma factors to
      intracellular pH measurements. Plasma digoxin-like factor (DLF) was assessed in
      both patients and normotensive controls. Neutrophil intracellular pH was
      significantly lower in the pre-eclamptic patients (7.15 +/- 0.050) compared with
      the normotensive pregnant controls (7.36 +/- 0.027; P<.001). NHE-1 activity (in
      mmol/L/min) was significantly higher in the pre-eclamptics (32.4 +/- 1.9)
      compared with the normotensive neutrophils (27.1 +/- 1.6; P =.038). Times course
      experiments showed that mean pre-eclamptic intracellular pH increased from 7.11
      +/- 0.049 to 7.25 +/- 0.043 after 2 hours of incubation. DLF, measured as amount
      of inorganic phosphate liberated from adenosine triphosphate (ATP), was
      significantly lower when plasma from the pre-eclamptic patients was incubated
      with the enzyme compared with plasma from the normotensive pregnant women (54.9
      +/- 2.6 nmol/mL plasma v 63.91 +/- 1.7 nmol/mL plasma, n = 6, P =.018 unpaired
      Student's t test). The results suggest that elevated NHE-1 activity and
      intracellular acidosis are intermediate phenotypes in women who have pre
      eclampsia. Intracellular pH may have been affected by plasma as shown in the time
      course experiments. DLF, an inhibitor of Na(+)/K(+)ATPase, may contribute to this
      intracellular acidosis in pre-eclamptic neutrophils.

PMID- 12524669
TI  - Platelet sodium-proton exchanger and phospholipid-dependent procoagulant activity
      in patients with type 2 diabetes.
AB  - Platelet Na(+)/H(+) exchanger (NHE) activity, phospholipid-dependent thrombin
      generation, and platelet factor 3 (PF3) availability were measured in 83 type 2
      diabetics and in 40 age- and sex-matched healthy subjects. Na(+)/H(+) exchanger
      activity was significantly increased in diabetic patients in comparison to the
      controls (kappa = 4.29 +/- 0.71 x 10(-3) x s(-1) v 3.21 +/- 0.64 x 10(-3) x s(
      1), P <.00001). However, there was no significant difference between subjects
      with (kappa = 4.28 +/- 0.75 x 10(-3) x s(-1)) and without (kappa = 4.26 +/- 0.32
      x10(-3) x s(-1)) arterial hypertension, as well as between patients with normo-
      and microalbuminuria or overt proteinuria (kappa = 4.26 +/- 0.58 x 10(-3) x s(
      1), kappa = 4.47 +/- 0.93 x 10(-3) x s(-1) and kappa = 4.07 +/- 0.38 x10(-3) x s(
      1), respectively). Comparatively high NHE activity was observed in the group of
      patients with hemoglobin A(1c) (HbA(1c)) less than 7.5%. Multiple regression
      analysis revealed that the factors independently related to platelet Na(+)/H(+)
      exchanger activity were: total PF3 activity (beta = 0.77, P =.011) and
      triglyceride (TG) concentration (beta = 0.44, P =.039). Phospholipid-dependent
      thrombin generation and PF3 availability were also enhanced in all plasma
      fractions of diabetic patients, especially in platelet-poor plasma (PPP) and
      platelet-free plasma (PFP) (P <.0001 and P <.00001, respectively). There was a
      positive correlation between NHE activity and thrombin generation, as well as
      with PF3 availability in all plasma fractions. Our results suggest that enhanced
      platelet Na(+)/H(+) exchanger activity associated with raised phospholipid
      dependent procoagulant activity may increase the risk of vascular damage in type
      2 diabetic patients.

PMID- 12524668
TI  - Level of glycogen stores and amount of ingested glucose regulate net carbohydrate
      storage by different mechanisms.
AB  - The respective effects of the level of glycogen stores and the size of the
      glucose load on the pathways of carbohydrate (CHO) metabolism were compared over
      the 5-hour period following glucose ingestion in normal human subjects. For this
      purpose, labeling of the oral glucose load with [3-(3)H]- and [U(14)C] glucose
      was combined with indirect calorimetry. In group I, 75 g glucose was given to
      subjects who had either been "fed" with intravenous (IV) glucose or fasted for
      13, 24, or 36 hours, or 4 days. In fed versus 4-day-fasted subjects, net CHO
      storage averaged approximately 15 versus 63 g/5 h (P <.001). About 83% of the
      increase in fasted subjects was due to suppression of glycogen breakdown, with
      only minimal stimulation of glycogen synthesis from oral glucose. Over the whole
      range of nutritional conditions tested, a strong positive correlation existed
      between basal CHO oxidation and glycogen breakdown occurring during the oral
      glucose tolerance test (OGTT), suggesting that the initial degree of repletion of
      hepatic glycogen stores is a major determinant of postprandial glycogen turnover.
      In group II, OGTTs with 33 and 100 g glucose were compared in 13-hour-fasted
      subjects. Net storage rose from approximately -6 to approximately 37 g/5 h (P
      <.001) solely because of an increase in glycogen synthesis with no inhibition of
      glycogen turnover. Overall, these results show that the initial dietary state and
      the size of the glucose load modulate postprandial net CHO accumulation by
      different mechanisms.

PMID- 12524670
TI  - The independent and combined effects of 16 weeks of vigorous exercise and energy
      restriction on body mass and composition in free-living overweight men--a
      randomized controlled trial.
AB  - This study assessed the effects of 16 weeks of energy restriction and vigorous
      exercise on body mass and body composition. Sixty sedentary men, mean body mass
      (mean +/- SD) 96.3 (13.9) kg and mean age 42.4 (5.0) years, were randomly
      assigned to either continue their normal energy intake or restrict energy intake
      by 4,186 to 6,279 kJ. d(-1). Each group was further randomized to a control light
      exercise program, or a vigorous exercise program for 3 half-hour sessions per
      week. Vigorous exercise improved maximum oxygen consumption (Vo(2max)) by
      approximately 24% (0.56 [95% confidence interval, 0.47 to 0.65) L. min(-1), P
      <.001) with no significant changes in body mass, body composition, or fat
      distribution. With energy restriction there was a significant reduction in body
      mass of 10.1 (8.0 to 12.2) kg, lean body mass (LBM) of 2.4 (1.5 to 3.3) kg, fat
      mass (FM) of 7.7 (5.9 to 9.6) kg, waist to hip ratio (WHR) of 0.03 (0.01 to
      0.04), and the sum of 6 skinfolds of 26.9 (15.4 to 38.4) mm (P <.001). Combining
      vigorous exercise with energy restriction resulted in no further changes in
      measures of body composition. We conclude that in sedentary free-living
      overweight men, 16 weeks of energy restriction, but not vigorous intensity
      exercise, results in substantial reductions in body mass, LBM, and FM.
      Furthermore, vigorous intensity exercise when combined with energy restriction
      did not modify or enhance the changes in body fat distribution or body
      composition seen with energy restriction alone. The independent effects of
      exercise to induce changes in body mass and composition in the longer term in
      free-living overweight subjects on an energy-restricted diet deserve further
      study.

PMID- 12524671
TI  - Lipoprotein alterations in hemodialysis: differences between diabetic and
      nondiabetic patients.
AB  - Both renal failure and type 2 diabetes may contribute synergistically to the
      dyslipemia of diabetic renal failure with the development of atherosclerosis as
      the possible consequence. It has not yet been conclusively evaluated whether
      diabetic patients with end-stage renal failure under maintenance hemodialysis
      (HD) show accentuated alterations in plasma lipids and lipoproteins in comparison
      to nondiabetics under HD. These abnormalities would involve hepatic lipase
      activity and the regulation of triglyceride-rich lipoprotein metabolism. The
      purpose of the present study was to evaluate whether type 2 diabetic patients
      undergoing HD exhibited a lipid-lipoprotein profile different from that of
      nondiabetic hemodialyzed patients. We compared plasma lipids, apoprotein (apo) A
      I and B, and lipoprotein parameters among 3 groups: 25 type 2 diabetics, 25
      nondiabetics, both undergoing HD, and 20 healthy control subjects. Intermediate
      density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated by
      sequential ultracentrifugation. Hepatic lipase activity was measured in
      postheparin plasma. Both groups of HD patients showed higher triglyceride and IDL
      cholesterol (P <.001), and lower high-density lipoprotein (HDL) cholesterol (P
      <.01) and apo A-I (P <.001) levels compared to the control group, even after
      adjustment for age and body mass index (BMI). However, no differences were found
      in lipid, lipoprotein, and apoprotein concentrations between diabetic and
      nondiabetic HD patients, except for high LDL triglyceride content of diabetic HD
      patients (P <.01). Nondiabetics undergoing HD also presented higher LDL
      triglyceride levels than controls (P <.05). LDL triglyceride correlated with
      plasma triglycerides (r = 0.51, P <.001). A lower LDL cholesterol/apo B ratio was
      found in each group of HD patients in comparison to controls (P <.02). Comparing
      the diabetic and nondiabetic patients, hepatic lipase activity remained
      unchanged, but significantly lower than control subjects (P <.001). Hepatic
      lipase correlated with log-triglyceride (r = -0.31, P <.01), IDL cholesterol (r =
      -0.41, P <.001), and LDL triglyceride (r = -0.32, P <.01). In conclusion, both
      diabetic and nondiabetic HD patients shared unfavorable alterations in lipid
      lipoprotein profile not different between them but different from a healthy
      control group. The only difference between the groups of HD patients was a
      significant LDL triglyceride enrichment, which correlated negatively with hepatic
      lipase activity. Lipoprotein abnormalities in HD patients would enhance their
      risk for the development of atherosclerosis.

PMID- 12524672
TI  - Treatment of primary hypothyroidism during pregnancy: is there an increase in
      thyroxine dose requirement in pregnancy?
AB  - We studied the dose requirements of thyroxine (T(4)) and serum concentrations of
      thyrotropin-stimulating hormone (TSH) and free T(4) in 16 pregnant women with
      primary hypothyroidism due to autoimmune thyroid disease (ATD, n = 11) or
      thyroidectomy (n = 5). All patients had been advised by their obstetricians to
      take prenatal vitamins enriched with iron ( approximately 90mg/tablet) and
      calcium ( approximately 200 mg/tablet), known to inhibit absorption of T(4). We
      asked patients to take their vitamins 4 hours after ingesting T(4) in the
      morning. The mean T(4) dose of 0.10 +/- 0.01 (mean +/- SEM, mg/d) during
      pregnancy did not differ significantly from that (0.09 +/- 0.005) before or after
      (0.10 +/- 0.01) pregnancy. Similarly, mean serum TSH of 2.7 +/- 0.28 mIU/L during
      pregnancy did not differ significantly from that before (2.2 +/- 0.47) or after
      (3.2 +/- 1.31) pregnancy. The mean serum free T(4) concentration during pregnancy
      (16 +/- 0.97 pmol/L) was significantly (P <.05) lower than that (22 +/- 1.5)
      before or after (23 +/- 2.2) pregnancy and similar to that observed with our free
      T(4) measurement technique in normal (healthy) pregnant women. We next examined
      the data separately in patients with ATD and thyroidectomy. The mean T(4) dose
      (0.08 +/- 0.009) and TSH (2.4 +/- 0.29) during pregnancy in 11 ATD patients did
      not differ appreciably from those before (T(4) dose, 0.08 +/- 0.0006; TSH, 2.7 +/
      0.54) or after (T(4) dose 0.09 +/- 0.0063; TSH, 4.1 +/- 1.91) pregnancy.
      Similarly, the mean T(4) dose (0.12 +/- 0.022, n = 5) during pregnancy in
      thyroidectomized patients was similar to that before (0.12 +/- 0.017, n = 3) or
      after (0.12 +/- 0.022) pregnancy. However, serum TSH increased significantly,
      albeit within the normal range, during pregnancy in thyroidectomized patients
      (3.2 +/- 0.62, n = 5 v 0.41 +/- 0.017, n = 3, P <.05) and it (1.3 +/- 0.60)
      decreased significantly (P <.05) after pregnancy. Our data suggest that (1) the
      dose requirement of T(4) does not change systematically in pregnancy in most
      hypothyroid women. There may occur a modest increase in T(4) dose requirement
      during pregnancy in some thyroidectomized patients; (2) diminished absorption of
      T(4), possibly related to ingestion of exogenous agents (eg, iron, calcium,
      vitamins), may have contributed to previous suggestions of substantial increased
      T(4) requirement in pregnancy; (3) ingestion of T(4) dose absorption-inhibiting
      agents some 4 hours away from T(4) markedly diminishes or obviates their effect
      in many patients. Although many hypothyroid patients may not require an
      adjustment in their T(4) dose during pregnancy, it is prudent to monitor all such
      patients carefully as the consequences of inadequate therapy may be very
      important.

PMID- 12524673
TI  - A 60 Hz magnetic field does not affect the incidence of squamous cell carcinomas
      in SENCAR mice.
AB  - Two groups of SENCAR mice were treated with a single dose of carcinogen and then,
      for 23 weeks, with a chemical tumor promoter to induce skin tumors. During this
      period, one group was coexposed to a 2 mT power frequency (60 Hz) magnetic field,
      while the other was exposed to sham conditions. Application of the tumor promoter
      ceased after 23 weeks, but the exposure to sham conditions or magnetic fields
      continued for an additional 29 weeks. No difference was found between the two
      groups of mice in terms of the incidence of total tumors (P =.297) or squamous
      cell carcinomas (SSC) (P =.501). In summary, there was no evidence to support the
      hypotheses that 60 Hz magnetic fields (MF) can influence the development of
      either papillomas or SSC under our defined experimental conditions. The overall
      results add to previous animal studies that find no association between exposure
      to 60 Hz MF and the incidence of benign or malignant tumors.

PMID- 12524674
TI  - Exposure of human peripheral blood lymphocytes to electromagnetic fields
      associated with cellular phones leads to chromosomal instability.
AB  - Whether exposure to radiation emitted from cellular phones poses a health hazard
      is at the focus of current debate. We have examined whether in vitro exposure of
      human peripheral blood lymphocytes (PBL) to continuous 830 MHz electromagnetic
      fields causes losses and gains of chromosomes (aneuploidy), a major "somatic
      mutation" leading to genomic instability and thereby to cancer. PBL were
      irradiated at different average absorption rates (SAR) in the range of 1.6-8.8
      W/kg for 72 hr in an exposure system based on a parallel plate resonator at
      temperatures ranging from 34.5-37.5 degrees C. The averaged SAR and its
      distribution in the exposed tissue culture flask were determined by combining
      measurements and numerical analysis based on a finite element simulation code. A
      linear increase in chromosome 17 aneuploidy was observed as a function of the SAR
      value, demonstrating that this radiation has a genotoxic effect. The SAR
      dependent aneuploidy was accompanied by an abnormal mode of replication of the
      chromosome 17 region engaged in segregation (repetitive DNA arrays associated
      with the centromere), suggesting that epigenetic alterations are involved in the
      SAR dependent genetic toxicity. Control experiments (i.e., without any RF
      radiation) carried out in the temperature range of 34.5-38.5 degrees C showed
      that elevated temperature is not associated with either the genetic or epigenetic
      alterations observed following RF radiation-the increased levels of aneuploidy
      and the modification in replication of the centromeric DNA arrays. These findings
      indicate that the genotoxic effect of the electromagnetic radiation is elicited
      via a non-thermal pathway. Moreover, the fact that aneuploidy is a phenomenon
      known to increase the risk for cancer, should be taken into consideration in
      future evaluation of exposure guidelines.

PMID- 12524675
TI  - Growth and yield of winter wheat (Triticum aestivum L.) and corn (Zea mays L.)
      near a high voltage transmission line.
AB  - The objective of this study was to determine the effects of an electromagnetic
      field from a high voltage transmission line on the yield of agricultural crops
      cultivated underneath and near the transmission line. For 5 years, experiments
      with winter wheat and corn were carried out near the 380 kV transmission line
      Durnrohr (Austria)-Slavetice (Czech Republic). Different field strengths were
      tested by planting the crops at different distances from the transmission line.
      The plants were grown in experimental plots (1.77 m2), aligned to equal electric
      field strengths, and were cultivated according to standard agricultural practice.
      The soil for all plots was homogenized layer-specifically to a depth of 0.5 m to
      guarantee uniform soil conditions in the plant root environment. The soil was
      sampled annually for determinations of carbon content and the behavior of
      microbial biomass. During development of the vegetation, samples were collected
      at regular intervals for growth rate analyses. At physiological maturity, the
      plots (n = 8) were harvested for grain and straw yield determinations. The
      average electric and magnetic field strengths at four distances from the
      transmission line (nominal distances: 40, 14, 8, and 2 m) were between 0.2 and
      4.0 kV/m and between 0.4 and 4.5 micro T, respectively. No effect of the field
      exposures on soil microbial biomass could be detected. The wheat grain yields
      were 7% higher (average of 5 years) in the plots with the lowest field exposure
      than in the plots nearer to the transmission line (P <.10). The responses of the
      plants were more pronounced in years with drought episodes during grain filling
      than in humid years. No significant yield differences were found for corn yields.
      The extent of the yield variations attributed to the distance from the
      transmission line was small compared to the observed annual variations in
      climatic or soil specific site characteristics.

PMID- 12524676
TI  - Effect of the meniscus at the solid/liquid interface on the SAR distribution in
      Petri dishes and flasks.
AB  - Several authors have reported that the meniscus as occurring at the walls of
      Petri dishes and flasks (solid-liquid interface) can significantly affect the SAR
      distribution in the entire dish and flask, while others have ignored this effect.
      In this study, this effect has been comprehensively analyzed by numerical means
      supported by theoretical considerations. The focus is on E polarization, which
      results in the most homogeneous exposure for monolayer cell cultures and
      therefore is the most often applied polarization in exposure setups for risk
      assessment studies. This includes setups based on TEM cells, waveguides, radial
      transmission lines (RTL), and HF chambers. The conclusion of this study is that
      the meniscus and its size have a significant effect on the strength and
      homogeneity of the induced SAR distribution. Hence, the meniscus needs to be
      accounted for in the determination of the averaged SAR as well as in the
      uncertainty assessment. It has also been demonstrated that a voxel size of less
      than 0.2 mm is needed to predict the SAR values for a monolayer of cells
      accurately.

PMID- 12524677
TI  - The effect of strong static magnetic field on lymphocytes.
AB  - We investigated whether static electromagnetic fields (EMFs) at a flux density of
      4.75 T, generated by an NMR apparatus (NMRF), could promote movements of Ca2+,
      cell proliferation, and the eventual production of proinflammatory cytokines in
      human peripheral blood mononuclear cells (PBMC) as well as in Jurkat cells, after
      exposure to the field for 1 h. The same study was also performed after activation
      of cells with 5 mg/ml phytohaemagglutinin (PHA). Our results clearly demonstrate
      that static NMRF exposure has neither proliferative, nor activating, nor
      proinflammatory effects on both normal and PHA activated PBMC. Moreover, the
      concentration of interleukin-1beta, interleukin-2, interleukin-6, interferon, and
      tumour necrosis factor alpha (TNFalpha) remained unvaried in exposed cells.
      Exposure of Jurkat cells statistically decreased the proliferation and the
      proliferation indexes, which 24 and 48 h after exposure were 0.7 +/- 0.29 and
      0.87 +/- 0.12, respectively. Moreover, in Jurkat cells the [Ca2+]i was higher
      than in PBMC and was reduced significantly to about one half after exposure. This
      is consistent with the decrease of proliferation and with the low levels of IL-2
      measured. On the whole, our data suggest that NMRF exposure failed to affect the
      physiologic behaviour of normal lymphomonocytes. Instead in Jurkat cells, by
      changing the properties of cell membranes, NMRF can influence Ca2+ transport
      processes, and hence Ca2+ homeostasis with improvement of proliferation.

PMID- 12524678
TI  - Circularly polarised MF (500 micro T 50 Hz) does not acutely suppress melatonin
      secretion from cultured Wistar rat pineal glands.
AB  - Magnetic fields (MF, 50 Hz) have been proposed to affect melatonin production in
      mammals; however, there is very little data about the mechanism by which this
      possible interaction may occur. Here we describe results from the first study in
      which circularly polarised 50 Hz MF have been administered to isolated pineals in
      highly controlled conditions. Melatonin release from isolated Wistar rat pineal
      glands, dissected 2 h after light onset ZT 2, was measured in a flow through
      culture system, during and after exposure to a 4 h MF similar in nature and
      magnitude to that produced in extremely close proximity to a high voltage power
      line (500 micro T 50 Hz circularly polarised). Melatonin release from isolated
      pineals was comparable to that observed in previous studies, plateauing to
      approximately 100 pg/ml/30 min. No significant alterations in pineal melatonin
      release were caused by exposure to the MF when compared to sham exposure (< 1
      micro T). These results suggest that if the circadian system is acutely
      responsive to MF exposure of this nature, an intact circadian axis may be
      necessary in order to observe an effect on the production on melatonin from the
      pineal gland

PMID- 12524679
TI  - A four coil exposure system (tetracoil) producing a highly uniform magnetic
      field.
AB  - We propose a magnetic field exposure system (tetracoil) for in vitro and in vivo
      experiments, composed of two couples of circular coils satisfying a spherical
      constraint, whose characteristics are chosen in order to maximize the uniformity
      region of the magnetic field. Analytical calculations and computer simulations
      show that our system, as compared to the other most largely used magnetic field
      exposure systems, represents an optimal compromise in terms of field uniformity,
      accessibility for biological experiments, and ratio between overall dimension and
      uniformity region.

PMID- 12524680
TI  - ELF magnetic fields induce internalization of gap junction protein connexin 43 in
      Chinese hamster lung cells.
AB  - We have previously demonstrated that exposure of Chinese hamster lung (CHL) cells
      to 50 Hz magnetic fields (MFs) and/or 12-O-tetradecanoylphorbol-3-acetate (TPA)
      inhibited gap junctional intercellular communication (GJIC). To explore and
      compare the mechanisms of GJIC inhibition induced by extremely low frequency
      (ELF) MF and TPA, the number and localization of connexin 43 (C x 43) were
      studied. The localization of C x 43 was determined with indirect
      immunofluorescence histochemical analysis and detected by confocal microscopy
      after exposing CHL cells to 50 Hz sinusoidal magnetic field at 0.8 mT for 24 h
      without or with TPA (5 ng/ml) for the last 1 h. The C x 43 levels in nuclei and
      in cytoplasm were examined by Western blotting analysis. The results showed that
      the cells exposed to MF and/or TPA displayed individual plaques at regions of
      intercellular contact, which were fewer than the normal cells in number, while
      the number of C x 43 in cytoplasm increased and congregated near the nuclei.
      Western blot analysis further demonstrated the quantity of changes in location of
      Cx43. These results suggest that reduction of C x 43 at regions of intercellular
      contact may be one of the mechanisms of GJIC inhibition induced by ELF MF.

PMID- 12524681
TI  - Anti-pressor effects of whole body exposure to static magnetic field on
      pharmacologically induced hypertension in conscious rabbits.
AB  - Acute effects of whole body exposure to static magnetic field (SMF) on
      pharmacologically induced hypertension in a conscious rabbit were evaluated.
      Hypertensive and vasoconstrictive actions were induced by norepinephrine (NE) or
      a nonselective nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-l-arginine
      methyl ester (l-NAME). The hemodynamics in a central artery of the ear lobe was
      measured continuously and analyzed by penetrating microphotoelectric
      plethysmography (MPPG). Concurrently, blood pressure (BP) changes in a central
      artery, contralateral to that of the MPPG measured ear lobe, were monitored.
      Magnetic flux densities were 5.5 mT (Bmax), the magnetic gradient peaked in the
      throat at the level of approximately 0.09 mT/mm, and the duration of exposure was
      30 min. The results demonstrated that under normal physiological conditions
      without treatment of pharmacological agents, there were no statistically
      significant differences in the hemodynamics and BP changes between the sham and
      the SMF exposure alone. Under pharmacologically induced hypertensive conditions,
      the whole body exposure to nonuniform SMF with peak magnetic gradient in the
      carotid sinus baroreceptor significantly attenuated the vasoconstriction and
      suppressed the elevation of BPs. These findings suggest that antipressor effects
      of the SMF on the hemodynamics under NE or l-NAME induced high vascular tone
      might be, in part, dependent on modulation of NE mediated response in conjunction
      with alteration in NOS activity, thereby modulating BPs.

PMID- 12524682
TI  - ELF fields and photooxidation yielding lethal effects on cancer cells.
AB  - The lethal effect on human cancer cells was studied under three types of
      treatment: A) an ELF pulsed sinusoidal of 50 Hz electromagnetic field (PEMF) with
      amplitudes between 10 and 55 mT; B) the field and a cytostatic agent (actinomycin
      C); and C) the field, the cytostatic agent, which has a photodynamic effect, and
      exposure to a halogen lamp. The results show a decreasing vitality of human K-562
      and U-937 cancer cells in suspension with each additional treatment. Combination
      with other parameters as hyperthermia and/or hyperacidity could yield high
      killing rates by this noninvasive method.

PMID- 12524683
TI  - Prominent expression of lysyl oxidase during mouse embryonic cardiovascular
      development.
AB  - By mRNA differential display in mouse hearts, lysyl oxidase (Lox), a key enzyme
      catalyzing cross-links in elastin and collagens, was found to be up-regulated
      between embryonic days 11 (E11) and 13 (E13). This was confirmed by
      semiquantitative RT-PCR. We analyzed its spatio-temporal expression pattern by in
      situ hybridization in regard to the development of myocardial cells, endocardial
      cushion tissue, aortic arch vessels, and epicardium.

PMID- 12524684
TI  - Establishment of cadherin-based intercellular junctions in the dermal papilla of
      the developing hair follicle.
AB  - During hair follicle development, mesenchymal cells aggregate to form the dermal
      papilla with hair-inducing activity. However, the cellular mechanisms underlying
      the aggregative behavior of dermal papilla cells are less known. The present
      study demonstrates that cadherin-based intercellular junctions interconnect
      dermal papilla cells in developing hair follicles of mice. It is shown that as
      mesenchymal cells aggregate to be surrounded by epithelium in developing hair
      follicles, cadherin-11 comes to exhibit the dotted patterns of distribution. The
      appearance of the dot-like distribution of the molecule is concomitant with the
      formation of intercellular junctions in the mesenchymal aggregate, which make a
      tightly packed population of cells with little extracellular space. At later
      stages of the development, although extracellular space reappears in the dermal
      papilla, the cells remain interconnected by well-developed intercellular
      junctions, where cadherin-11 as well as beta-catenin is localized. Taking into
      consideration the normal hair development in cadherin-11 mutant mice, it might be
      that multiple cadherins are responsible for the establishment of intercellular
      junctions in the dermal papilla and serve to maintain the aggregative behavior of
      the cells.

PMID- 12524685
TI  - Ultrastructural morphology of adrenal chromaffin cells indicative of a process of
      piecemeal degranulation.
AB  - Chromaffin cells of the mouse adrenal medulla were found by transmission electron
      microscopy (TEM) to exhibit ultrastructural changes suggestive of piecemeal
      degranulation (PMD), a unique model of cell secretion characterized by the slow
      release of granule materials without granules opening to the cell exterior. The
      expression of PMD was recognized in both adrenaline- and noradrenaline-containing
      cells. Ultrastructural changes included specific granule and cytoplasmic
      morphologies. In adrenaline-releasing cells the granule content was loosely
      packed or condensed, and surrounded by a clear halo. In noradrenaline-storing
      cells, the granule material appeared asymmetrically arranged and exhibited
      characteristic "semilunar" electron-dense domains within the granule chambers.
      Notably, altered granules did not fuse with each other or with the plasma
      membrane, and were intermingled with normal, resting granules. Large, empty
      cytoplasmic containers or vacuoles filled with partially dissolved matrices were
      frequently observed. In addition, both adrenaline- and noradrenaline-storing
      cells presented a rich supply of membrane-bound, smooth vesicles (50-200 nm
      diameter) that were either free in the cytoplasm or attached to granules. The
      finding of ultrastructural features characteristic of PMD in adrenal chromaffin
      cells suggests that such a secretory model may be an alternative secretory
      pathway to regulated exocytosis. Moreover, these results support the hypothesis
      that PMD may be a general degranulation pattern in cells involved in paracrine
      endocrine secretion.

PMID- 12524686
TI  - Embryonic development of coronary vasculature in rats: corrosion casting studies.
AB  - The aim of this study was to analyze the development of coronary vessels at
      different stages of embryonic life in rats using corrosion casts and scanning
      electron microscopy (SEM). We studied morphologic details of vessel maturation,
      expansion, and pattern formation from the stage of development when the coronary
      system forms patent connections with the aorta and the right atrium (embryonic
      day 16 (ED16)) to full-term fetus (ED21). The internal surface morphologies of
      the arterial and venous vessel walls were different and were dependent on the
      distance from the orifice and the capillary system. They also depended on the
      maturation state of a given vessel. In various branches of the coronary system we
      demonstrated round, fusiform or polygonal, endothelial cell imprints. The
      capillary network was dense, however, at the early stages of development, it
      formed a thin layer over the myocardium. By ED21 capillaries assumed an
      orientation parallel to the long axes of the cardiac myocytes. During all stages
      of development, different forms of angiogenesis by intussusceptive growth were
      observed. Splitting of the vessel wall occurred in two or three points along the
      vessel, forming two- or three-link chains. Certain areas of vessels resembled
      doughnuts, from which several sister vessels originated. The coronary arteries
      were situated deep within the myocardial wall. The major coronary veins were
      mostly located on the surface of the capillary plexuses of the myocardial wall.
      In conclusion, this method of vessel casting enables the detection of
      angiogenesis by intussusceptive growth, and the visualization of a capillary's
      position to the myocardial wall, thickness of the capillary plexuses, and the
      internal surface morphology of major vessels.

PMID- 12524687
TI  - p75NTR in the spleen: age-dependent changes, effect of NGF and 4-methylcatechol
      treatment, and structural changes in p75NTR-deficient mice.
AB  - In addition to their well-known actions within the nervous system, neurotrophins
      and their receptors are involved in immune system functioning, as demonstrated by
      their wide distribution in lymphoid tissues and their in vitro actions on
      immunocompetent cells. Nevertheless, the in vivo roles of neurotrophin-receptor
      systems in lymphoid tissues, as well as the scope of their influence throughout
      development and adulthood, are yet to be clarified. In the present study, we used
      combined morphological and immunohistochemical techniques to investigate the
      presence and cellular localization of p75NTR, the pan-neurotrophin receptor
      protein, in rat spleen from newborns to aging individuals, and the structural and
      innervation changes in the spleens of p75NTR-deficient mice. In rats, p75NTR was
      expressed by splenic nerve fibers and dendritic cells in an age-regulated
      fashion, with maximal expression detected at 2 weeks. Consistently, the spleens
      of newborn mice lacking this receptor protein showed no signs of ingrowing
      sympathetic fibers, along with an absence of defined white pulp areas. The
      present findings suggest a prolonged role of p75NTR in the physiology of the
      spleen; at least during the embryonic development period, the receptor may be
      critical for correct innervation and compartmentalization processes to occur.

PMID- 12524688
TI  - Effects of experimental diabetes on the structure and ultrastructure of the
      coagulating gland of C57BL/6J and NOD mice.
AB  - Diabetes mellitus can lead to reproductive disorders that in turn result in
      weakened fertility brought about by morphofunctional changes in the testes and
      accessory sex glands. However, doubts persist concerning the basic biology of the
      secretory epithelial cells and the stroma of the coagulating gland of diabetic
      mice. Thus, the objective of the present study was to analyze the histological
      and ultrastructural changes associated with stereology of the coagulating gland
      of mice with alloxan-induced diabetes, and of spontaneously diabetic mice.
      Sixteen mice of the C57BL/6J strain, and eight non-obese diabetic (NOD) mice were
      used. The animals were divided into three groups: 1) control (C), 2) alloxan
      diabetic (AD), and 3) NOD. Thirty days after the detection of diabetic status in
      group 2, all of the animals were killed and then perfused with Karnovsky's
      solution through the left cardiac ventricle. The coagulating gland was then
      removed and processed for morphometric study by light microscopy and electron
      microscopy. The results showed thickening of the stroma, atrophy of secretory
      epithelial cells, and disorganization of the organelles involved in the secretory
      process in both NOD and alloxan-induced mice. Thus, it may be concluded that the
      coagulating gland suffered drastic morphological changes, and consequently
      impaired glandular function, in the presence of diabetes mellitus type I in both
      NOD and AD mice.

PMID- 12524689
TI  - Stereologic characterization and spatial distribution patterns of Betz cells in
      the human primary motor cortex.
AB  - Betz cells are giant motoneurons located in layer Vb of the primate primary motor
      cortex. We conducted stereological analyses of Betz cells and neighboring
      pyramidal cells from the brains of six neurologically normal elderly humans to
      determine their volume, total number, and spatial distribution, and to relate
      these data to functional localization. The distribution of cellular volumes
      exhibits a bimodal pattern, delineating two different subpopulations. Betz cell
      volumes follow a mediolateral gradient, the largest Betz cells being located on
      the most medial part of the motor cortex. Additionally, the shape of Betz cells
      varies between the rostral and caudal parts of the primary motor cortex,
      supporting the notion that there are anatomically distinct zones in primary motor
      cortex. The total number of Betz cells per hemisphere accounts for about one
      tenth of the total number of pyramidal cells in layer Vb. Analysis of spatial
      distribution using Voronoi tessellation revealed maximal clustering of Betz cells
      in a zone situated two-thirds from the midline along the mediolateral axis of the
      primary motor cortex. These data suggest that Betz cells have a discrete
      subregional distribution that may correspond to certain aspects of the functional
      parcellation of area 4. These results may offer a histological correlate of
      functional imaging studies and are relevant in the context of neurodegenerative
      diseases such as amyotrophic lateral sclerosis, progressive supranuclear palsy,
      and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia, and in studies
      of normal brain aging.

PMID- 12524690
TI  - Specific biological functions of vacuolar-type H(+)-ATPase and lysosomal cysteine
      proteinase, cathepsin K, in osteoclasts.
AB  - We report the effects of specific and potent inhibitors of vacular-type H(+)
      ATPase and lysosomal cysteine proteinases, cathepsins, on the ultrastructure,
      expression of these enzymes, and resorptive functions of cultured osteoclasts.
      Osteoclasts were formed by co-culture of marrow cells and calvarial primary
      osteoblasts of ddY mice. Formed osteoclasts were cultured on dentine slices for 6
      48 hr with either an H(+)-ATPase inhibitor, bafilomycin A1, or a cysteine
      proteinase inhibitor, E-64. In control cultures with no additive, osteoclasts
      were structurally characterized by the development of ruffled borders and clear
      zones, and formed many resorption lacunae on dentine slices. Both H(+)-ATPase and
      cathepsin K were strongly expressed in the ruffled borders of these osteoclasts.
      In bafilomycin A1-treated cultures, osteoclasts lacked ruffled borders, and
      resorption lacuna formation was markedly diminished. This effect of bafilomycin
      A1 on osteoclast structure was reversible by removal of the compound. Bafilomycin
      A1 treatment altered the subcellular localization and decreased the expression of
      H(+)-ATPase molecules. H(+)-ATPase expression was observed throughout the
      cytoplasm, but not along the plasma membranes facing dentine slices. On the other
      hand, E-64 treatment did not affect the ultrastructure of osteoclasts and the
      expression of enzyme molecules. Although E-64 showed no effect on
      demineralization of dentine slices, it dose-dependently reduced resorption lacuna
      formation. Our results suggest that 1) bafilomycin A1 dose-dependently inhibits
      resorption lacuna formation via inhibition of ruffled border formation, 2) H(+)
      ATPase expression is closely associated with the cytoskeleton of osteoclasts, and
      3) E-64 treatment decreases the depth of resorption lacunae, by inhibition of
      secreted cathepsin K activity, but does not impair ruffled border formation and
      the associated expression of H(+)-ATPase and cathepsin K in osteoclasts.

PMID- 12524691
TI  - Recapitulation of oral mucosal tissues in long-term organotypic culture.
AB  - To test the influence of fibroblasts on epithelial morphology and expression of
      keratinocyte proteins and barrier lipids, we bioengineered homotypic and
      heterotypic oral mucosae and skin using cultured adult human cells. Fibroblasts
      were allowed to modify collagen type I gels for 2 weeks before keratinocytes were
      added. The organotypic cultures were then grown at the air-liquid interface for 4
      weeks. In homotypic combinations, epithelial morphology and protein expression
      closely mimicked those in vivo. In heterotypic combinations, the morphology
      resembled that in vivo and keratinocytes expressed their typical markers, except
      when skin keratinocytes were recombined with alveolar fibroblasts; they expressed
      K19, K4, and K13, which is similar to oral mucosal epithelia rather than to the
      epidermis. Morphologically, the stratum corneum layers were typical for the
      epithelial tissues. Grafting the bioengineered cultures to the backs of Nude mice
      did not change the results, suggesting that our findings are not merely a culture
      phenomenon. Lipid profiles of the homotypic combinations mimicked the profiles
      found in the normal epithelial tissues, except that the engineered alveolar
      epithelium expressed more ceramide 2 than that in vivo. In the heterotypic
      combinations, keratinocytes appeared to control the lipid profile, except in the
      combination of skin keratinocytes with alveolar fibroblasts, wherein the ceramide
      profile appeared to be partly that of alveolar epithelium and partly that of
      epidermis. These results suggest that cultured adult fibroblasts and
      keratinocytes are sufficient to recapitulate graftable oral tissues, and, except
      for alveolar fibroblasts, the type of fibroblast had little influence on
      keratinocyte differentiation.

PMID- 12524692
TI  - Correlation of knee-joint cartilage morphology with muscle cross-sectional areas
      vs. anthropometric variables.
AB  - We tested the hypothesis that muscle cross-sectional areas (MCSAs) are more
      highly (and independently) correlated with cartilage morphology than are body
      height and weight, and that the physiological reduction of cartilage thickness
      with aging is associated with a proportional, age-dependent decrease in MCSAs. In
      59 asymptomatic individuals (23-75 years old), morphological parameters of the
      knee cartilages (volume, thickness, and bone-cartilage interface area), and MCSAs
      were determined from magnetic resonance imaging (MRI) data. Multiple regression
      models were used to calculate which proportion of the variability of the normal
      cartilage morphology can be predicted based on independent variables. MCSAs and
      body height and weight showed correlation coefficients of +0.66, +0.60, and
      +0.25, respectively, with knee-joint cartilage volume. The correlation
      coefficients with cartilage thickness were +0.44, +0.35, and +0.24, respectively.
      Age accounted for a significant (P<0.01) reduction in cartilage thickness, but
      there was no proportional change of MCSAs. Approximately 76% of the variability
      of the knee cartilage volume could be predicted from independent variables in a
      multiple regression model with MCSAs contributing significant, independent
      information. In conclusion, we find that MCSAs are more highly correlated with
      cartilage morphology than are body height and weight. The significant decrease in
      cartilage volume and thickness with age is not associated with a proportional
      decrease in MCSAs.

PMID- 12524693
TI  - The right to assisted suicide and euthanasia.

PMID- 12524694
TI  - Evidence-based Rheumatology.

PMID- 12524695
TI  - Radiotracer chemistry in 2002.

PMID- 12524696
TI  - Physics in nuclear medicine: a year of tangible progress.

PMID- 12524697
TI  - Findings of scientific misconduct.

PMID- 12524698
TI  - Preventing obesity. Hidden sugars in foods undermine strategies to reduce obesity
      and diabetes.

PMID- 12524699
TI  - Preventing obesity. Doctors underestimate obesity.

PMID- 12524701
TI  - Anesthesiologist direction and patient outcomes.
AB  - The relationship between physicians and nurses in the delivery of anesthesia care
      is politically and financially charged, and hotly debated. Against this backdrop,
      federal regulators have proposed dropping a Medicare requirement that nurse
      anesthetists be supervised by a physician. Proponents note that the new
      regulations would resolve inconsistencies between Medicare supervisory
      requirements and state law, while opponents voice concerns for patient safety.
      This Issue Brief describes the current controversy, and summarizes a newly
      published study that suggests differences in patient outcomes depending on the
      nature and level of anesthesiologist involvement in surgical care.

PMID- 12524702
TI  - How managed care growth affects where physicians locate their practices.
AB  - Managed care has had a profound effect on physician practice. It has altered
      patterns in the use of physician services, and consequently, the practice and
      employment options available to physicians. But managed care growth has not been
      uniform across the United States, and has spawned wide geographic disparities in
      earning opportunities for generalists and specialists. This Issue Brief
      summarizes new information on how managed care has affected physicians' labor
      market decisions and the impact of managed care on the number and distribution of
      physicians across the country.

PMID- 12524703
TI  - Community benefits: how do for-profit and nonprofit hospitals measure up?
AB  - The rise of the for-profit hospital industry has opened a debate about the level
      of community benefits provided by non-profit hospitals. Do nonprofits provide
      enough community benefits to justify the community's commitment of resources to
      them, and the tax-exempt status they receive? If nonprofit hospitals convert to
      for-profit entities, would community benefits be lost in the transaction? This
      debate has highlighted the need to define and measure community benefits more
      clearly. In this Issue Brief, the authors develop a new method of identifying
      activities that qualify as community benefits, and propose a benchmark for the
      amount of benefit a nonprofit hospital should provide.

PMID- 12524704
TI  - Comparing VA and non-VA health care: the case of post-stroke rehabilitation.
AB  - The Department of Veterans Affairs (VA) runs the largest integrated health system
      in the country, and provides care to nearly 4 million patients each year. It has
      been dogged by persistent doubts about its efficiency and quality of care,
      despite numerous quality improvement programs and an extensive reorganization in
      1995. In fact, recent studies have found that health care in the VA compares
      favorably with non-VA systems, in areas such as preventive care and treatment for
      acute myocardial infarction. This Issue Brief summarizes a comparison in another
      area-inpatient rehabilitation for stroke- and highlights the difficulty and
      complexity of assessing quality across systems of care.

PMID- 12524705
TI  - When data conflict with practice: rethinking the use of prophylactic antibiotics
      before dental treatment.
AB  - Concern is growing about the overuse of antibiotics and the subsequent rise in
      antibiotic-resistant bacteria. Antibiotics are commonly used to prevent heart
      valve infections in susceptible patients undergoing dental or other surgical
      procedures. Although this practice has been standard for nearly 50 years, little
      evidence exists that it works. This Issue Brief summarizes a population-based
      study that challenges the link between dental procedures and heart valve
      infections, and illustrates the difficulty in incorporating new evidence into
      existing guidelines and longstanding practices.

PMID- 12524706
TI  - Does managed care gatekeeping affect African Americans' access to emergency care?
AB  - A number of national initiatives have focused attention on persistent racial and
      ethnic disparities in health and health care. The rising tide of improvements in
      health has not raised all boats; in some cases, the health gap between whites and
      minorities has widened. Although many social and economic forces contribute to
      this gap, inequitable access to health care also plays a part. This Issue Brief
      examines a common strategy that managed care organizations use to reduce
      emergency department visits--gatekeeping--and describes a study of the
      differential impact it may have on African Americans.

PMID- 12524707
TI  - Cause for concern: nurses' reports of hospital care in five countries.
AB  - According to most experts, the U.S. faces a growing shortage of registered
      nurses, threatening the quality of care hospitals can provide. In the setting of
      nurse shortages and simultaneous concern about patient safety, nurses' job
      satisfaction and their assessment of quality of care become critical. This Issue
      Brief highlights a cross-national survey that describes nurses' perceptions of
      their hospital work environment, and identifies core problems in work design and
      workforce management in five countries.

PMID- 12524708
TI  - Connections between AIDS and homelessness.
AB  - Although the links between health and environment are well known, interventions
      that target these associations in order to improve health are rare. Health and
      social service agencies often function independently of one another, maintaining
      separate, unlinked databases. For example, relationships among homelessness,
      AIDS, and tuberculosis have been noted, but services have not focused on the
      intersecting populations these conditions affect. This Issue Brief summarizes
      efforts to merge databases and provide policymakers with information to guide
      housing, social service, and health care resources. The investigators identify
      risk factors associated with AIDS among the homeless, and homelessness among
      people with AIDS.

PMID- 12524709
TI  - State helmet laws and motorcycle rider death rates.
AB  - Motorcycles are the most dangerous form of motorized transportation. Per vehicle
      miles traveled, motorcyclists are about 3 times as likely as passenger car
      occupants to be injured in a crash, and 16 times as likely to die. Because the
      majority of these deaths are caused by head injury, safety advocates have
      recommended mandatory use of motorcycle helmets. Others contend that state laws
      mandating helmet use infringe on motorcyclists' rights, and question whether such
      laws really reduce motorcycle deaths and injury. Scientific evidence cannot
      address the appropriate balance between personal freedom and public safety, but
      it can address the effectiveness of mandatory helmet laws. This Issue Brief
      summarizes a new analysis of the effects of motorcycle helmet laws on death
      rates, and points out the need to account for other potential factors when
      comparing death rates across states.

PMID- 12524710
TI  - Trends in cigarette smoking among high school students--United States, 1991-2001.

PMID- 12524711
TI  - World Space Congress: a vision quest.

PMID- 12524712
TI  - Developing better artificial bones.

PMID- 12524713
TI  - [Recurring headache. Myelin vacuoles in type 1 neurofibromatosis].

PMID- 12524714
TI  - Q fever: still a mysterious disease.

PMID- 12524715
TI  - XIV International AIDS Conference, Barcelona, 7-12 July 2002.

PMID- 12524716
TI  - [Unusual cause of acute impairment of consciousness. Decompensated hydrocephalus
      caused by blockage of the foramini Monroi due to enlarged basilar artery].

PMID- 12524717
TI  - Building our future--increasing diversity in the dietetics profession: a summary
      of the ADA diversity mentoring project.

PMID- 12524718
TI  - A rebuttal.

PMID- 12524719
TI  - Israeli clinic serves children of low-income families.

PMID- 12524720
TI  - How to market the successful dental practice.

PMID- 12524721
TI  - Web site provides education, information on dental decay, cavities.

PMID- 12524722
TI  - NYU College of Dentistry to present Irwin Smigel prize in aesthetic dentistry.
      Inaugural prize will be presented to Dr. Ronald E. Goldstein.

PMID- 12524723
TI  - Effects of smoking on periodontal disease can be reversed, study finds.

PMID- 12524724
TI  - Research provides further importance of good oral health in pregnant women.

PMID- 12524725
TI  - Soft tissue biopsy techniques for the general practitioner, Part 1.

PMID- 12524726
TI  - Lasers in dentistry: where we are today.

PMID- 12524727
TI  - Temporary crowns and bridges made easy.

PMID- 12524728
TI  - Oral health in cancer therapy: evaluating and preventing oral complications.

PMID- 12524729
TI  - Redefining the principles of restorative dentistry: lessons from microscope
      assisted dentistry.

PMID- 12524731
TI  - Overcoming objections: providing professionally made custom mouthguards.

PMID- 12524730
TI  - Case report: treatment of amlodipine associated gingival overgrowth in
      periodontitis patients.

PMID- 12524732
TI  - A new protocol for halitosis treatment.

PMID- 12524733
TI  - Overcoming the money taboo.

PMID- 12524734
TI  - A tale of four incisors, Part 2.

PMID- 12524735
TI  - The 4 M's of dental success, Part 1.

PMID- 12524736
TI  - Immediate dies for in-office indirect resin restorations.

PMID- 12524738
TI  - Picture-perfect teeth?

PMID- 12524737
TI  - Changing the dental profession by revolution, not evolution.

PMID- 12524740
TI  - Putting the spin on conservative treatment.

PMID- 12524739
TI  - The wear and tear of teeth.

PMID- 12524741
TI  - Overtreatment.

PMID- 12524742
TI  - Fluoride levels best in tap water, study finds.

PMID- 12524743
TI  - Clinical management of a worn dentition with a new polycentric occlusal system.

PMID- 12524744
TI  - Aesthetic dilemma: technique for augmenting a resorbed pontic site.

PMID- 12524745
TI  - Conservative repair of a fractured lateral incisor: comparative treatment options
      and case history.

PMID- 12524746
TI  - Breakthrough treatment: orthodontics made easier, faster, and more beautiful.

PMID- 12524747
TI  - Simple daily radiology quality control in private practice.

PMID- 12524748
TI  - Provisionalization of the anterior aesthetic case.

PMID- 12524749
TI  - Exposing the myths of high-tech dentistry: roadblocks in technology, techniques,
      and teamwork.

PMID- 12524751
TI  - Indirect laminate veneers: an excellent option to correct elective aesthetic
      problems.

PMID- 12524750
TI  - Aesthetics and biocompatibility: strong, electroformed, pure gold for PFM crowns
      and bridges.
AB  - The plethora of base-mental alloys and metal-free restorations and ever rising
      cost of palladium alloys has given this full-feature PFM system a definite place
      in modern dentistry. Thanks to the minimum tooth reduction necessary, GES
      PureGold has a number of clinical and aesthetic advantages. The system's gold
      substructures are my choice because they provide natural color beneath ceramics,
      a high degree of biocompatibility, and exquisite marginal integrity.

PMID- 12524753
TI  - Laser treatment not the best option.

PMID- 12524752
TI  - Hybrid composites: providing the best for conservative restorations.

PMID- 12524754
TI  - Important points not addressed.

PMID- 12524756
TI  - Sweetener determined safe in drugs, mouthwashes, and toothpastes.

PMID- 12524755
TI  - Salaried vs fee-for-service dentists.

PMID- 12524757
TI  - Women's role in dentistry celebrated.

PMID- 12524758
TI  - New test provides ease in detecting colon cancer.

PMID- 12524759
TI  - The efficiency of modern endodontics. Interview by Phillip Bonner.

PMID- 12524760
TI  - Orascopic endodontics: changing the way we "think" about endodontics in the 21st
      century.
AB  - Orascopic endodontics has helped bring visualization to what has literally been a
      "blind" specialty. The ease of operation and better operating ergonomics of fiber
      optic instrumentation has allowed the endodontist to identify and treat
      endodontic etiology more efficiently. The metamorphosis of understanding
      endodontics from an in vivo perspective is changing the way we "think" about the
      practice of endodontics. Prior to intracanal visualization, the cognitive process
      of determining when the canal was ready for obturation was merely an educated
      guess based on years of in vitro instrumentation research and postoperative
      follow-up studies.

PMID- 12524761
TI  - The sixteen deadly sins: a comprehensive approach to accurate diagnosis.

PMID- 12524762
TI  - A simple, cost-effective method of denture duplication.

PMID- 12524763
TI  - Tricks for matching shades: the color match game.

PMID- 12524764
TI  - Interproximal reduction and lower incisor extraction in adult aesthetic
      orthodontics.

PMID- 12524765
TI  - The 21st-century dentist. The CEO of supervised periodontal care.

PMID- 12524766
TI  - Considerations in the removal of mandibular tori.

PMID- 12524768
TI  - Pitfalls in radiographic interpretation, Part 1.

PMID- 12524767
TI  - Direct and indirect composites for the restoration of decimated dentition in
      elderly patients.

PMID- 12524769
TI  - Dentistry takes the cybercure: scheduling, consultations, records move to the
      net.

PMID- 12524770
TI  - Your staff and the new patient.

PMID- 12524771
TI  - Digital radiography: don't get caught in a costly mistake.

PMID- 12524772
TI  - Solving problems.

PMID- 12524773
TI  - Breakthrough treatment or broken?

PMID- 12524774
TI  - Orthodontics and TMD.

PMID- 12524775
TI  - Employee management. The fifth in a series of 6 articles for the new dentist or a
      "refresher for the already knowledgeable".

PMID- 12524776
TI  - Surgeon General's report charts course of action against dental and oral
      diseases.

PMID- 12524777
TI  - The nation's oral health report card grade? C-minus.

PMID- 12524778
TI  - The use of cast gold restorations: scientific basis and clinical technique.
AB  - A technique has been presented for restoring a bicuspid tooth with a cast gold
      restoration. Gold is the standard of comparison for all other dental materials,
      and is unsurpassed for exactness of fit and longevity. With the introduction of
      new dental restorative materials, it is important to remember that gold is a time
      tested option for restoration of posterior teeth.

PMID- 12524779
TI  - Snoring and sleep apnea: the dentist's role in treatment.

PMID- 12524780
TI  - The cosmetic temporary.

PMID- 12524781
TI  - Negotiating root canals to their termini.

PMID- 12524782
TI  - Articaine: pharmacology and clinical use of a recently approved local anesthetic.

PMID- 12524783
TI  - Aesthetic dentistry: taking a comprehensive approach.

PMID- 12524784
TI  - Use of new technologies in an aesthetic restorative case.

PMID- 12524785
TI  - Videoconferencing--the ultimate consult: the future is now.

PMID- 12524786
TI  - How to create digital mosaics and pseudo panoramic x-rays.

PMID- 12524787
TI  - The 4th M: mastery of dentistry, Part 2: Lasers and laminates.

PMID- 12524788
TI  - Taking care of business: collections (payment optional?).

PMID- 12524789
TI  - The one-appointment indirect ceromer restoration.

PMID- 12524790
TI  - Coaching: a progressive new paradigm.

PMID- 12524791
TI  - One-day implant system provides minimal surgical load for patients.

PMID- 12524792
TI  - Aesthetic dilemma: restoring the quality of life in a cleft lip, cleft palate
      patient.

PMID- 12524793
TI  - A tale of four incisors, Part 1.

PMID- 12524794
TI  - Aesthetic and functional advantages of current all-ceramic crowns: a case
      history.

PMID- 12524795
TI  - Mastering the impression technique for simple to complex treatments.

PMID- 12524796
TI  - Three canals in the mandibular second premolar.

PMID- 12524797
TI  - Diagnosing oral lesions. Interview by Phillip Bonner.

PMID- 12524798
TI  - Practical infection control in the dental office.

PMID- 12524799
TI  - Ergonomics in the dental office.

PMID- 12524800
TI  - Digital dentistry in the 21st century.

PMID- 12524801
TI  - Air abrasion for the 21st century.

PMID- 12524802
TI  - Dentists: give it up.

PMID- 12524803
TI  - How to sell a treatment plan: codiagnosing.

PMID- 12524804
TI  - Soft tissue biopsy techniques for the general practitioner, Part 2.

PMID- 12524805
TI  - Open your vertical and smile, Part 2: Porcelain-fused-to-gold, full-mouth
      rehabilitation.

PMID- 12524806
TI  - Submandibular sialolithiasis.

PMID- 12524807
TI  - Restoration of two fractured, endodontically treated teeth using nonmetallic
      materials.

PMID- 12524808
TI  - Saving a fixed bridge using a new microhybrid system.

PMID- 12524809
TI  - Emergencies associated with local anesthetics.

PMID- 12524810
TI  - Restoring aesthetics and vertical dimension in a bruxism case.

PMID- 12524811
TI  - Nickel-titanium rotary systems: review of existing instruments and geometries.

PMID- 12524812
TI  - Reattachment of a broken tooth fragment following dental trauma.

PMID- 12524813
TI  - Wear resistance of resin systems.

PMID- 12524814
TI  - New technologies for interdisciplinary solutions.

PMID- 12524815
TI  - All the right moves: integrating technology & ergonomics into your patient care
      environment.

PMID- 12524816
TI  - Brain wave synchronizers: a potential tool for reducing dental stress and
      anxiety.

PMID- 12524817
TI  - Surgeon General warns of oral health importance.

PMID- 12524818
TI  - Drug may slow tumor growth in men with advanced prostate cancer.

PMID- 12524819
TI  - Loss of cuspid guidance: a functional and aesthetic dilemma.

PMID- 12524820
TI  - Aesthetic dilemma: maximizing aesthetics through proper tooth form and alignment.

PMID- 12524821
TI  - Overcoming obstacles to placing posterior direct resin restorations.

PMID- 12524822
TI  - Assessing occlusal forces quantitatively on metal-free restorations.

PMID- 12524823
TI  - Temporomandibular disorders.

PMID- 12524824
TI  - The best of both worlds: combining metal and ceromer for clinical success.

PMID- 12524825
TI  - Dental schools take leadership role in continuing education for aesthetic
      dentistry. Interview by Phillip Bonner.

PMID- 12524826
TI  - Problems with amalgam: physical and chemical instability.

PMID- 12524827
TI  - A guide to buying a dental laser.

PMID- 12524828
TI  - Stressed out? Put it in perspective.

PMID- 12524829
TI  - A simple, effective two-step impression technique.

PMID- 12524830
TI  - New research finds link between gum disease and acute heart attacks.

PMID- 12524831
TI  - Dental, oral and craniofacial data resource center established.

PMID- 12524832
TI  - Risk management.

PMID- 12524833
TI  - Microdentistry: challenging traditional paradigms and offering a new standard of
      care in dentistry. Interview by V. Kim Kutsch.

PMID- 12524834
TI  - The replacement of congenitally missing teeth: a novel approach using a
      combination of restorative techniques.

PMID- 12524835
TI  - Cosmetic dentistry for patients who can't afford it.
AB  - As I noted earlier, all things being equal, patients prefer tooth-colored
      restorations. This technique has removed virtually all the barriers to treatment
      and makes things a lot more equal. There's the cost factor (Dramatically
      reduced!) There's the fear-of-needle factor (Gone!) There's the time factor
      (Minimized!). In fact, prepping and placing these occlusal veneers is so fast I
      can now do 8 to 10 amalgam rehabs in one appointment. Doing so many in a short
      time is extremely profitable, even at the reduced fee. This technique certainly
      does not qualify as "great dentistry," but it brings "desire-motivated" cosmetic
      dentistry to an entirely new universe and those patients are appreciative.
      They're even referring their friends! In my practice, veneering amalgam has
      brought cosmetic dentistry to many patients who would never agree to have their
      restorations replaced with traditional composite resin. And it has brought me
      several additional thousand dollars in collections each month. So this is a
      classic "win-win" situation. Patients are getting cosmetic restorations they
      didn't think they could afford, and I'm making a great profit doing it.

PMID- 12524836
TI  - MIND: a method of diagnosing oral pathology.

PMID- 12524837
TI  - The role of the microscope in 21st century endodontics: visions of a new
      frontier.
AB  - In endodontics, the microscope is indispensable. Clinicians are discovering that
      every facet of endodontics is better, safer, and easier. Microscopic endodontics
      is a new technology that emphasizes visual information, rather than tactile
      information. The learning curve can be fairly steep, but it is one worth
      climbing. Future controlled studies should document an improvement of endodontic
      outcomes. This is becoming more true as dentistry becomes more extensive and
      expensive, and needs to last longer and longer. The days of "easy cases" are much
      fewer, even for the general practitioner. Lastly, there is a groundswell
      conversation, at least in the endodontic community, that the benefits of the
      microscope are beyond biology. Clinicians experience a greater sense of personal
      and professional fulfillment because they are not achieving what is "good
      enough," but aspiring to "what is possible."

PMID- 12524838
TI  - What you don't know can hurt you (and your patients).
AB  - The goal of modern dentistry is to return patients to oral health in a
      predictable fashion. The partial and complete edentulous patient may be unable to
      recover normal function, aesthetics, comfort, or speech with a traditional
      removable prosthesis. The aesthetics of the edentulous patient are affected as a
      result of bone atrophy. Continued resorption leads to irreversible facial
      changes. An implant stimulates the bone and maintains its dimension in a manner
      similar to healthy natural teeth. As a result, the facial features are not
      compromised by lack of support. Implant prostheses often offer a more predictable
      treatment course than traditional restorations. Thus, the profession and the
      public are becoming increasingly aware of this dental discipline. Between 1983
      and 1987 there was a tenfold increase in the number of dentists placing implants
      and a fourfold increase in the number of implants inserted. Manufacturers' sales
      have increased from a few million dollars to more than $200 million. Almost every
      professional journal and lay publication now carries advertisements for implants.
      Implant dentistry has finally been accepted by organized dentistry. All US dental
      schools now teach some awareness of implant dentistry. The current trend to
      expand the use of implant dentistry will continue until every restorative
      practice uses this modality for abutment support of both fixed and removable
      prostheses. Do not be the straggler and ignore the advantages of dental implants,
      because what your patients don't know can hurt them.

PMID- 12524839
TI  - Prehybridization: an alternative method for dentin bonding.

PMID- 12524840
TI  - Options.

PMID- 12524841
TI  - TMD debates.

PMID- 12524842
TI  - Partnership formed to improve children's oral health.

PMID- 12524843
TI  - Perils of tooth loss and ill-fitting dentures fuel implant popularity.

PMID- 12524844
TI  - The dental PPO: the preferred way to gain the benefits of network-based plan
      participation.

PMID- 12524845
TI  - Cosmetic makeover simulations in a windows environment: Part 1.

PMID- 12524846
TI  - The maxillary tuberosity: indications and simple technique for reduction.

PMID- 12524847
TI  - COX-2 inhibitors: new drugs for the management of pain and inflammation.

PMID- 12524848
TI  - Orthodontic treatment as a prelude to dental implant-supported restorations: the
      need for change in team communication procedures.

PMID- 12524849
TI  - The visual diagnostic try-in: a dramatic tool for aesthetic treatment acceptance.

PMID- 12524850
TI  - Current concepts for preparing the root canal system.

PMID- 12524851
TI  - Managing emergency pediatric dental trauma.

PMID- 12524852
TI  - Winning the mind of the patient: the missing link in periodontal treatment
      acceptance.

PMID- 12524853
TI  - Use of a resin-ionomer for subgingival restorations (external root resorption):
      case report.

PMID- 12524854
TI  - The human stomatognathic system: a scientific approach to occlusion.

PMID- 12524855
TI  - The 4th M: mastery of dentistry, Part 3: Lasers & laminates.

PMID- 12524856
TI  - Comparison of time to anesthesia for block, infiltration, and intraosseous local
      anesthetic injections: a clinical study.

PMID- 12524857
TI  - The Bell system: direct resin methodology.

PMID- 12524858
TI  - Who wants to be a millionaire? (or, how to go from point "this" to point "that").

PMID- 12524859
TI  - Kudos.

PMID- 12524860
TI  - Dental education.

PMID- 12524861
TI  - Highly wired? Dentists embracing new computer technologies, albeit cautiously.

PMID- 12524862
TI  - Dental-related illnesses ravaging school attendance.

PMID- 12524863
TI  - Perils of cigar and pipe smoking documented.

PMID- 12524864
TI  - Stronger oral cancer screening advocated. Misinformation, lack of knowledge
      foreshadowing awareness of disease.

PMID- 12524865
TI  - Finishing: the essence of exceptional endodontics.

PMID- 12524866
TI  - Winning the mind of the patient, Part 2: Why teeth need crowns.

PMID- 12524867
TI  - Indirect aesthetic posterior restorations.

PMID- 12524868
TI  - Geriatric hygiene: it's not all black and white.

PMID- 12524869
TI  - Hybrid protocol for restoring a tissue abutment-supported fixed bridge.

PMID- 12524870
TI  - Maxillary anterior implant treatment: a protocol for aesthetic success.
AB  - This case represents how predictable results can be obtained in a difficult
      situation if a tried-and-true protocol is closely followed. An atraumatic
      surgical technique, followed by controlled healing through correct implant
      placement and the use of a custom-healing abutment, set up the success of the
      soft tissue component of the case. Meticulous laboratory communication, combined
      with correct restoration selection, was the final step in the creation of
      lifelike results.

PMID- 12524871
TI  - The care of dental patients with diabetes mellitus, Part 1.

PMID- 12524872
TI  - Why some physicians envy dentists: the applications service provider.
AB  - To summarize, here's what I get from my ASP. My staff and I can access our
      schedules, patient information, etc, any time and from anywhere--not just from
      the office PC. All I need is a standard Internet browser and a connection to the
      Internet. Only authorized personnel have access to my data. My online practice
      management system is password protected and operates with Verisign SSL--the
      highest level of Internet security. All information is stored in my secure
      database, which my ASP backs up and replicates continuously. Dental. PackOnline
      even operates dual servers. In case one server has a problem, they just switch to
      the other server, so I never have to worry about "down-time." I can give patients
      access to their own information online-treatment plans, patient education
      material, balances, etc, in a highly private and confidential manner. I can share
      patient information, x-rays, and other materials online with colleagues,
      specialists, and labs, again in a highly confidential manner. I send out billing,
      recalls, claims, and more automatically because my ASP has real-time connections
      to service providers. No more time spent printing, folding, stamping cards,
      billing, or processing claims. This is a tremendous cost and time saver!

PMID- 12524873
TI  - Current adhesive dentistry as an alternative to amalgam: case history.

PMID- 12524875
TI  - Dental insurance: do you or don't you?

PMID- 12524874
TI  - Current concepts and future trends for periodontal disease and periodontal
      therapy, Part 2: Classification, diagnosis, and nonsurgical and surgical therapy.
AB  - As noted in both this and the previous review, our understanding of the etiology,
      diagnosis, and treatment of the periodontal diseases is continuously evolving.
      Periodontology in the year 2001 is different than what it was 20 years ago, and
      the specialty will be different 20 years in the future. Assessment of patients
      will be more specific, and the development of risk profiles will allow
      identification of individuals who require greater or lesser amounts of care.
      Therapy can then be directed to the specific needs of each patient. Surgical
      periodontics will be focused on regeneration, not resection. Lastly, as patients
      continue care on a maintenance schedule, their status will be assessed by
      sensitive tests that will predict the onset of an active phase of disease so that
      appropriate interceptive treatment can be provided.

PMID- 12524876
TI  - Using diagnostic wax-ups in aesthetic cases.

PMID- 12524877
TI  - Converting emergency patients to long-term patients.

PMID- 12524878
TI  - Four myths of a successful practice.

PMID- 12524879
TI  - TMD revisited.

PMID- 12524880
TI  - The future of dentistry.

PMID- 12524881
TI  - Managing dental diseases in the 21st century. Irrigation as an adjunct to home
      care shows promising results.

PMID- 12524882
TI  - Periodontist survey identifies problems, reveals astonishing excuses.

PMID- 12524883
TI  - Bulimia continues to ravage oral health.

PMID- 12524884
TI  - Implants (and smiles) more popular than ever.

PMID- 12524885
TI  - Glass ionomers revisited.

PMID- 12524886
TI  - Conservative restoration of posterior teeth: an introspective.

PMID- 12524887
TI  - Current concepts and future trends for periodontal disease and periodontal
      therapy, Part 1: Etiology, risk factors, natural history, and systemic
      implications.

PMID- 12524888
TI  - The predefined endodontic preparation: instrument and technique updates for the
      greater taper system.

PMID- 12524889
TI  - A combined carbon dioxide/erbium laser for soft and hard tissue procedures.

PMID- 12524890
TI  - Gender differences in oral health.

PMID- 12524891
TI  - Combining maxillary bar overdenture attachment systems: a case report.

PMID- 12524892
TI  - Posts and cores: when to use them.
AB  - The two overriding factors for successful post restoration are: 1. Retention,
      i.e., resistance to torsional forces. Published research is clear that threaded
      posts are the method of choice for the restoration of endodontically treated
      teeth in order to achieve optimal success. Prethreaded and self-threaded are the
      two systems from which to choose. The words active and passive should be applied
      to the method of producing threads, not the posts. The most gentle way to produce
      a thread is with a thread cutter. 2. Stress distribution of some cylindrical
      threaded posts has been shown to be far superior to nonthreaded cylindrical and
      nonthreaded tapered posts. With the acceptance of threaded, cylindrical
      prefabricated posts, new terminology has evolved, and the use and meaning of
      these words has been made more precise.

PMID- 12524893
TI  - The single implant procedure: the general practitioner's role.

PMID- 12524894
TI  - Easy financial arrangements.

PMID- 12524895
TI  - [Recent advances in surgical technology--open MRI and "real-time" navigation].
AB  - Many advances of neurosurgery had been achieved about diagnostic and operative
      tools such as CT scan, MRI, stereotaxy, and microscope, in 20th century. However,
      intraoperative diagnostic tools are not sufficient for providing solid data. So
      we developed new operating system for 21st century (Intelligent Operating
      Theater: IOT). The IOT has an open MRI machine for intraoperative MR imaging that
      provides objective anatomical data and the "real-time" navigation updated with
      iMRI that navigates surgeons to the target area. The IOT has contributed to the
      improvement of the resection rate in brain tumor cases.

PMID- 12524896
TI  - [Classification and recent status of intraductal papillary tumor of the
      pancreas].

PMID- 12524897
TI  - Measurement of low level membrane proteins using bicinchoninic acid: modified
      procedures to eliminate interfering substances.
AB  - Accurate determination of low levels of protein in samples containing large
      amounts of interfering substances is rather difficult. Precipitation
      bicinchoninic acid (BCA) assay as reported can concentrate and partially
      decontaminate the protein by adding sodium deoxycholate (DOC) and trichloroacetic
      acid (TCA) to the sample. Yet, this procedure alone has been insufficient for
      analysis of highly contaminated samples. In this report, we describe an improved
      method, the DOC-TCA-washing-BCA method, which is composed of the DOC-TCA
      precipitation and a subsequent aqueous washing that eliminates many interfering
      substances. The protein concentrations in samples containing even large amounts
      of interfering substances (e.g. various sugars and some detergents) were well
      quantitated by this method. The modifications described here have enabled us to
      perform rapid and efficient removal of many interfering substances that are
      commonly used in protein purification, and to allow proteins to be detected above
      0.05 microgram and from a solution above 0.5 microgram/ml.

PMID- 12524899
TI  - [Acute and chronic leukemias. Current aspects of pathogenesis, diagnosis and
      therapy].

PMID- 12524900
TI  - [Pathogenesis and biology of leukemias].

PMID- 12524901
TI  - [Modern techniques in leukemia diagnosis].

PMID- 12524902
TI  - [Therapeutic strategies in acute myeloid leukemia].

PMID- 12524903
TI  - [Acute lymphatic leukemia in the adult. Diagnosis, risk groups and therapy].

PMID- 12524904
TI  - [Current therapy concepts in chronic myeloid leukemia. Study IV of the German CML
      Study Group].

PMID- 12524905
TI  - [Chronic lymphatic leukemia. Current therapy concepts].

PMID- 12524906
TI  - [Information availability on therapy studies in the acute and chronic leukemia
      competence network].

PMID- 12524907
TI  - [Skin exanthema in infectious illnesses. II. Skin exanthema in bacterial
      illnesses, dermatomycoses, epizoonoses].

PMID- 12524908
TI  - [An usual cause of acute lung edema requiring artificial respiration in a 25-year
      old patient. Adrenal pheochromocytoma].

PMID- 12524909
TI  - [Septic disease picture in a 33-year-old patient. Toxic shock syndrome].

PMID- 12524910
TI  - [Surgical therapy in thoracic aortic aneurysm].

PMID- 12524911
TI  - [Supplementation with minerals and trace elements. Iron, zinc and selenium].

PMID- 12524912
TI  - [Current topics and new perspectives in Diabetology. Report of the 37th Annual
      Congress of the German Diabetes Society, May 8-11, 2002, in Dresden].

PMID- 12524913
TI  - [100 years chronic inflammatory bowel diseases. How far have we come?].

PMID- 12524914
TI  - [Genetics and the environment. Has the picture become clearer?].

PMID- 12524915
TI  - [The mucosal immune system. How clear is the pathophysiology?].

PMID- 12524916
TI  - [Laboratory values, endoscopy and new imaging. What is the status of diagnosis?].

PMID- 12524917
TI  - [Standard therapy of ulcerative colitis. Evidence- and consensus-based
      recommendations].

PMID- 12524918
TI  - [Standard therapy of Crohn disease. Consensus-based recommendations].

PMID- 12524919
TI  - [Therapeutic innovations in chronic inflammatory bowel diseases with "biological
      therapy"--anti-TNF and more].

PMID- 12524920
TI  - [Probiotics and prebiotics--a renaissance?].

PMID- 12524921
TI  - [Effect of chronic inflammatory bowel diseases on fertility and pregnancy].

PMID- 12524922
TI  - [Surgical therapy of Crohn disease and ulcerative colitis. What must the
      internist know?].

PMID- 12524923
TI  - [Chronic inflammatory bowel diseases competence network. Results and significance
      for general practice].

PMID- 12524924
TI  - [Osteoporosis].

PMID- 12524925
TI  - [21-year-old patient with recurrent diarrhea, weight loss, leg edema and iron
      deficiency. Gluten sensitive sprue].

PMID- 12524926
TI  - [Drug therapy of invasive candidiasis and aspergillosis].

PMID- 12524927
TI  - [Acute hepatitis C--therapy with interferon alpha-2b]].

PMID- 12524928
TI  - [Precautionary principle: technical-procedural tool or arrogant fable?].

PMID- 12524929
TI  - [Precautionary principle and responsibility].

PMID- 12524930
TI  - [The lesson from the debate on hormone replacement therapy].

PMID- 12524931
TI  - [On hormone replacement therapy in menopause].

PMID- 12524932
TI  - [Pregnancy outcome, infant mortality and mother's education in Piedmont from 1980
      to 1995].
AB  - The paper describes 1980-1995 trends in social differences in reproductive
      outcomes and infant mortality in Piedmont, Italy. By means of a logistic model,
      risk differences by mothers'educational level were calculated for low
      birthweight, stillbirth, neonatal, postneonatal and infant mortality in four time
      periods (1980-83, 1984-87, 1988-91, 1992-95). Odds ratios of low birthweight for
      children born to mothers in the lowest educational class compared to the highest
      are slightly increasing (from 1.43 to 1.57), while those between highest and
      intermediate educational groups are small and steady. After adjustment for
      selected confounding variables, for which data were available, these differences
      are confirmed. Differences in risk for neonatal mortality between highest and
      intermediate educational groups have strongly reduced from the beginning of the
      Nineties, while they have increased between highest and lowest classes. Adjusting
      for birthweight, differences disappear. Postneonatal mortality is strongly
      related to low educational level and differences are widening: OR for lowest
      educational level has increased from 1.96 to 2.60. Even within a fairly good
      health system, social differences are present. Hospital assistance has always
      been equitable to all new-borns; social differences generate in the environment
      where pregnant women and infants live. Due to the high attributable risk on
      infant mortality, reduction in social differences in low birthweight should be
      considered a priority in public health policy in Piedmont.

PMID- 12524933
TI  - [Underreporting of AIDS cases in Lazio, Italy].
AB  - One of the most important aspect of any surveillance system is completeness. We
      conducted an evaluation of the completeness of the AIDS surveillance system
      (SSAIDS) of Lazio region. We estimated the underreporting of AIDS cases in SSAIDS
      of Lazio in the period 1996-1998 through a linkage with the regional Hospital
      Information System (HIS) for the same years. A logistic regression model was used
      to estimate the relative risk (Odds Ratios--OR) of being unreported by
      demographic and clinical characteristics. A total of 56 cases had not been
      reported in the period 1996-1998, corresponding to 3.6% of underreporting. The
      risk of not being reported was associated with undetermined value of CD4 at
      diagnosis of AIDS (OR 15.40), unknown modality of exposure (OR 3.15) and with
      AIDS defining illness at diagnosis (ADI) as mycobacteriosis (OR 11.65),
      encephalopaties (OR 4.47) and toxoplasmosis (OR 8.67). Differences were also
      observed by clinical centre of diagnosis. In conclusion, the degree of
      underreporting is lower in our region than in other countries and the SSAIDS has
      a high completeness in Lazio. In agreement with other studies, underreporting is
      more frequent for cases with undermined value of CD4 at diagnosis of AIDS and
      unknown modality of exposure. The results regarding ADI need further
      investigation.

PMID- 12524934
TI  - [Respiratory effects of exposure to chlorine vapors during a swimming pool
      accident in a recreational center in Rome].
AB  - When inhaled, chlorine is a highly irritating gas that can damage larger airways
      as well as distal lung structure. We examined the short-term respiratory effects
      of acute chlorine inhalation during a swimming pool accident. On October 22,
      1998, an emission of chlorine vapours occurred in the chlorinating maintenance
      procedures room of a recreational center in Rome. A total of 282 subjects (134
      children) inhaled hydrogen chloride and sodium hypochlorite. Most people received
      bronchodilators and cortisone at the emergency room; five children were
      hospitalised. A telephone follow-up was taken on 260 (92.2%) subjects to obtain
      information about duration of exposure (less than 3 minutes, 3-5 minutes, more
      than 5 minutes), intensity of exposure (not at all/a little, a fair amount, a
      lot), and acute respiratory symptoms. A total of 236 (90.7% of the target)
      individuals underwent clinical examinations, which took place 15-30 days after
      the accident. Lung function was measured in 184 people (82 children) after 15-30
      days. A multiple linear regression was run to test the association between
      chlorine exposure and lung function, separately in adults and in children. Acute
      respiratory symptoms occurred among 66.7% adults and 71.6% children. The
      incidence rates were highest among those who had chronic respiratory disease and
      had a longer duration of exposure. In about 30% of the subjects, respiratory
      symptoms persisted 15-30 days after the accident. Lung function levels were
      reduced among those who reported high intensity of exposure in comparison to
      those who reported low exposure, both in children and in adults (forced
      expiratory volume in one second, FEV1, ml differences: -109 (CI 95%: -310, 93)
      and -275 (CI 95%: -510, -40). Given high prevalence of potential exposed people,
      findings from this study should alert public health authority about the possible
      clinical consequences.

PMID- 12524935
TI  - [Compensated cases for asbestosis. A geographical analysis by Italian provinces].
AB  - During 1995-1999 among cases compensated by Italian National Institute for
      Insurance of Occupational Accidents (INAIL), asbestosis was classified as the
      second occupational disease after hypoacusia with the 7% of total cases. The
      present study describes the geographical distribution of 1.483 cases in men,
      notified to INAIL (and subsequently confirmed) during 1984-1992. Age-standardised
      incidence rates were calculated for the 93 Italian provinces. In addition,
      standardised incidence ratio (SIR) were computed, comparing the number of
      observed cases to the number of expected cases on the basis of age specific rates
      in the large geographical Italian areas (Northeast, Northwest, Centre and South
      and islands). Empirical Bayes estimates applying the Poisson-Gamma model were
      also estimated. The geographical distribution of standardised incidence ratios
      revealed a high excess risk for the province of Gorizia, Livorno, Massa Carrara,
      La Spezia, Trieste, Alessandria, Caltanissetta and a lower, but still
      significant, excess risk for the province of Siracusa, Ancona, Napoli, Genova,
      Reggio Emilia, Brindisi, Bergamo, Arezzo, Taranto, Pavia, Messina, Lecco and
      Varese. This study suggests the possibility to use the insurance files on
      asbestosis in order to estimate risks in Italy and to compare geographical
      clusters. Identification of provinces with significant excess number of
      compensated cases for asbestosis underscore the need for more detailed surveys
      aimed to detect conditions correlated with asbestos exposure and identifying
      persisting environmental pollution. Detailed enquiries are needed in particular
      in those provinces where excesses cannot be explained by current knowledge on
      circumstances of the presence of asbestos in the workplace.

PMID- 12524936
TI  - [Geographical estimates and prediction of cancer occurrences: fashion or
      necessity].

PMID- 12524937
TI  - [Health in an era of global free trade].

PMID- 12524938
TI  - [Oncologic patients: cure, care and information].

PMID- 12524939
TI  - [A new view of things].

PMID- 12524940
TI  - [Modern diagnostic imaging: MR urography].
AB  - MR-urography presents a new diagnostic approach to the urinary system, resulting
      in images comparable to those known from i.v.-urography. T2-weighted MR-urograms
      demonstrate static fluid without ionizing radiation or nephrotoxic contrast
      media. The excretory renal function can be examined by the use of gadolinium
      enhanced T1-urography. The degree and cause of ureteric obstruction can be
      diagnosed with high sensitivity and specificity. On the other hand, urolithiasis
      is frequently misdiagnosed by MR-urography and, in this case, spiral CT should be
      used. Pediatric or pregnant patients can be examined as well as donors before and
      patients after renal transplantation. Furthermore, in case of a tumor MR-imaging,
      including MR-angiography, is a potential diagnostic "all-in-one" approach.

PMID- 12524941
TI  - [Contrast-medium enhanced reflux ultrasound in children. A comparison with
      radiologic imaging up to now].
AB  - Voiding cystourethrography (VCUG) has long been the method of choice for the
      diagnosis of vesicoureteral reflux (VUR). Especially in the course of
      conservative treatment, the radiation dose involved might become quite high over
      the years. Since the development of such ultrasound echo-enhancing agents as
      Levovist (Schering, Germany), we now have the ability to assess the diagnostic
      efficacy of this agent in the evaluation of VUR with a view to replacing VCUG
      with the radiation-free ultrasound methodology. A total of 104 children with a
      mean age of 5.4 years were examined using echo-enhancing ultrasound after
      informed consent had been obtained from their parents. For control purposes, all
      children were examined by standard VCUG as well. The diagnosis of VUR was judged
      to be positive when microbubbles appeared in the ureter or renal pelvis.
      Correlations were sought between the sonographic findings and those obtained by
      standard VCUG. In 76 (37%) of the 208 ureter-kidney units investigated, VUR was
      detected by both technologies. VUR was diagnosed by ultrasonography only in 5
      units and by VCUG only only in 3 units. All reflux grades (I-V) were identified.
      The specificity and sensitivity of the contrast reflux ultrasound were
      significantly high. The long contrast time of up to 30 min combined with the high
      contrast effect resulted in convincing images with high levels of diagnostic
      confidence. Our results clearly demonstrate that the safety and accuracy of the
      diagnosis of VUR by means of contrast-enhanced ultrasound is statistically
      comparable to those of standard radiologic VCUG. Therefore, this methodology is
      an exceptional approach to reducing the number of children being exposed to
      ionising radiation especially during conservative follow-up of children with
      reflux.

PMID- 12524942
TI  - [Virtual endoscopy of the urinary tract].
AB  - This review article depicts the technique of virtual uro-endoscopy and its
      diagnostic value and highlights future aspects. The raw data are acquired using
      CT, MR, or ultrasound. Sufficient contrast between the wall of the hollow organ
      and its interior is reached by administering gas or contrast medium into the
      bladder or injecting contrast media i.v. After processing of these data, virtual
      endoscopic procedures can be watched on a screen in the same way as a cine-film
      of a conventional endoscopic operation. Virtual endoscopy is a reliable method
      with a high sensitivity for pathologies larger than 0.5 cm. It is not invasive,
      and there are situations that cause difficulties in conventional endoscopy (e.g.
      gross hematuria, diverticula, strictures) that cause no technical problems in
      virtual endoscopy. Problems encountered in virtual endoscopy are due to its poor
      sensitivity for pathologies smaller than 0.5 cm, for carcinoma in situ, and for
      ureteral calculi. So far there are no routine-indications for virtual endoscopy
      in urology. Nevertheless, it can be of additional value in diagnosis providing
      the indications are carefully controlled. In future, virtual endoscopy will
      probably become integrated into the spectrum of urologic diagnostics
      investigations.

PMID- 12524944
TI  - [The (11C) acetate positron emission tomography in prostatic carcinoma. New
      prospects in metabolic imaging].
AB  - The exact staging of prostate cancer is mandatory to allow selection of the
      appropriate primary therapy. In addition, if the PSA level rises again it is
      extremely important to find the site(s) of local recurrence or metastatic spread
      as soon as possible. However, with the morphological and metabolic imaging
      techniques currently available it is often not possible to answer these questions
      with adequate sensitivity and specificity, since small metastases < or = 1 cm in
      diameter are likely to remain undetected by them. In the last few years new
      radioactive labelled tracers have been introduced for use in positron emission
      tomography (PET), and it is hoped that the shortcomings in the diagnostic
      procedures used for prostate carcinoma might be compensated by their use. Besides
      11C- or 18F-labelled choline, [11C]Acetate is also attracting attention as a
      promising PET tracer. In this paper we review the various PET tracers available
      and evaluate the advantages and the drawbacks of [11C]Acetate in three case
      studies by comparing [11C]Acetate-PET with histology and with other imaging
      techniques. The use of [11C]Acetate appears to be feasible and helpful in the
      diagnosis of prostate carcinoma. However, its final value relative to other
      imaging techniques needs further investigation, with special reference to initial
      lymph node involvement, early localisation of recurrence and possible noninvasive
      differentiation between prostate cancer, prostatis and benign hyperplasia of the
      prostate.

PMID- 12524943
TI  - [Transrectal ultrasound of the prostate. Current status and prospects].
AB  - In recent years the role of ultrasound in the diagnosis of prostate carcinoma has
      increased in importance. In view of the increasing incidence of prostate cancer,
      which is the most frequent malignant neoplasm in men, TRUS (transrectal
      ultrasound) is an important imaging method in the diagnosis of various prostate
      diseases. This paper provides a basic overview of physical and technical bases of
      TRUS investigation of the prostate. It concerns technical developments and modern
      techniques designed to improve its value in diagnosis. Impressive innovations in
      ultrasound equipment, particularly in the area of colour-coded Doppler sonography
      in association with microbubble-enhanced colour Doppler ultrasound, have given
      rise to justifiable hope of improvements in the early diagnosis of prostate
      cancer.

PMID- 12524945
TI  - [Magnetic resonance tomography of xanthogranulomatous pyelonephritis.
      Epidemiology, pathogenesis and symptoms].
AB  - Xanthogranulomatous pyelonephritis (XGP) is a rare chronic infection of the
      kidney. In this overview article we reevaluated the magnetic resonance imaging
      (MRI) findings of our four patients with histologically proven XGP and correlated
      them with the CT and ultrasound findings described in the literature.
      Additionally, we give an overview of the pathogenesis and epidemiology. The
      following criteria were found in MRI: hydronephrosis and/or urethral stricture,
      vesicoureteral reflux or neurogenic bladder depletion disorders, and calculus as
      the origin of urinary obstruction. Moreover, in contrast to normal
      pyelonephritis, XGP is accompanied by fatty deposits in the peripelvic
      parenchyma, which demonstrate contrast enhancement and form the typical so-called
      bear paw sign. As XGP is often accompanied by severe kidney failure, contrast
      enhanced CT with nephrotoxic contrast agents should be avoided and MRI should be
      performed instead. Because of proven reduced nephrotoxicity of gadolinium
      chelates, MRI seems to be superior to CT in patients with suspected XGP.
      Essential for the correct diagnosis is consideration of the complete medical
      history including recurrent pyelonephritis to avoid malpractice.

PMID- 12524946
TI  - [Prediction of calculus clearance after extracorporeal shock wave lithotripsy of
      calculi in the inferior kidney calices. Application of the artificial neural
      network].
AB  - The purpose of this retrospective study was to define prognostic factors which
      determine the stone clearance (SC) for lower caliceal stones after extracorporeal
      shock wave lithotripsy (ESWL) and to compare the prediction accuracy of
      artificial neural network analysis (ANNA) and standard computational methods.
      Since January 1995, 321 renal units in 310 patients with single or multiple
      inferior caliceal calculi of all sizes and compositions have been treated with
      ESWL (Lithotriptor: Piezolith 2500, Wolf company). The classification accuracy of
      ANNA in the test set was 94%, with a sensitivity of 95%, a specificity of 92%,
      and a receiver operating characteristic curve area of 0.966, results
      significantly better than those yielded by a logistic regression analysis
      (classification accuracy 77%, sensitivity 75%, specificity 81%, and ROC curve
      area 0.779). Patients with lower renal caliceal stones appear to have the best
      chance of successful ESWL when their body mass index (BMI) and urinary transport
      (UT) are normal, the infundibular width (IW) is 5 mm or more, and the
      infundibular ureteropelvic angle (IUPA) is 45 degrees or more. Stone size and
      composition, as factors of SC, are not statistically significant. After
      determining the angle, width, and UT in patients with optimal age and body mass
      suitable for ESWL, SC can be achieved irrespective of stone size and composition.

PMID- 12524947
TI  - [Preventing prostate carcinoma in men with familial disposition].
AB  - A family history is one of the strongest risk factors for prostate cancer (PC).
      We evaluated the detection rate of PC in relatives of 119 German PC families that
      took part in ongoing linkage analyses. Brothers of patients with sporadic
      prostate cancer aged < 55 years at onset were included as well. Responses were
      received from 120/196 (61.2%) individuals of the familial and 67/120 (55.8%) of
      the sporadic group. Findings (DRE, TRUS, PSA) were more often suspicious for
      carcinoma in the PC families. Prostate cancer was diagnosed in 6 (5.0%) and 2
      (2.99%) participants of the familial and the sporadic group, respectively. These
      detection rates tended to be higher than that of an age-matched subgroup of an
      unselected population in other European screening studies. The most important
      risk factor for the diagnosis of PC was a low average age at onset within the
      family. These data imply that prostate cancer screening in the high-risk group of
      men with familial predisposition cannot be assessed by population-based studies
      and should be evaluated separately.

PMID- 12524948
TI  - [Somatization disorders of the urogenital tract].
AB  - Diffuse symptoms in the urogenital region can frequently be explained by
      somatization disorders. Since they cannot be proven either by laboratory tests or
      with common technical diagnostic methods, somatization disorders should always be
      taken into consideration. Somatization disorders are to be considered functional
      disorders. Since somatization disorders due to muscular tension prevail in the
      urogenital region, the functional disturbance can be explained by the muscular
      tension. Subsequently, muscular tension causes the pathophysiological development
      of symptoms. As a rule they appear as myofascial pain or disorder. Muscular
      tension can have a psychic origin. The absence of urological findings is typical.
      Males and females between the ages of 16 and 75 can be affected by somatization
      disorders in the urogenital region. Somatization disorders due to muscular
      tension belong to the large group of symptoms due to tension. Diagnostic and
      therapeutic procedures as well as the pathophysiology of somatization disorders
      due to muscular tension are illustrated by two detailed case-reports.

PMID- 12524949
TI  - [Suprarenal leiomyoma of the vena cava. A rare differential adrenal gland tumor
      diagnosis].
AB  - Leiomyomas are benign tumors that can arise in the smooth muscle and can appear
      practically everywhere; hence, they must be taken into consideration as a rare
      possibility in the differential diagnosis of numerous tumors. While leiomyomas of
      the peripheral vessels are a relatively common finding, they are rarely found in
      the central vessels. Only a few cases of leiomyomas in the vena cava are known.
      In contrast to malignant leiomyosarcomas, leiomyomas usually grow towards the
      lumen. We report on the rare case of a leiomyoma in the inferior vena cava that
      appeared in the image to be located in the adrenal gland. Therefore,
      transperitoneal extirpation of the site was undertaken. It was only during
      surgery that a tumor emanating from the vessel wall became apparent. Thus, after
      an initial laparoscopic approach it became necessary to change to open resection
      of the tumor with cavotomy and resection of the vessel wall. The
      histopathological work-up revealed a benign leiomyoma and further imaging
      diagnostics gave no indication for the presence of metastases.

PMID- 12524950
TI  - [ICS preserves interdisciplinary character. 32nd Annual Meeting of the
      International Continence Society (ICS) in Heidelberg, 28-30 August, 2002].

PMID- 12524951
TI  - [Urinary calculi. 2: Metabolic defects, nutrition errors and metaphylaxis].

PMID- 12524952
TI  - [Effects of pneumatization of the temporal bone on the onset and course of acute
      mastoiditis].
AB  - Roentgenogram planimetry according to Schuller was made in 75 patients with acute
      mastoiditis (AM) to study correlations between the degree of pneumatization of
      the temporal bone and AM onset. It was found that complication of acute otitis
      media purulenta with AM takes place only in patients with well developed
      pneumatic system. Development of intracranial complications occurs in cases with
      wider area of the cell system. Mastoiditis arises because of inadequate treatment
      of acute inflammation of the middle ear and aditoanthral obstruction.

PMID- 12524953
TI  - [EEG and cardiac activity indices in patients with radiation-induced
      sensorineural hearing loss].
AB  - EEG was made in 47 patients with neurosensory hypoacusis (NSH) of radiation
      origin and 20 healthy subjects unexposed to radiation. These findings were
      compared to those on cardiac activity. The study shows that both in the temporal
      and occipital leads of patients with cardiac disorders alpha-rhythm amplitude and
      alpha-index are significantly less than in the control group. Thus, with
      deterioration of cardiac activity, NSH patients exposed to radiation exhibit more
      pronounced inhibition of bioelectric brain activity. This evidence should be
      considered in planning therapeutic and preventive measures in the above patients.
      The parameter of alpha-rhythm amplitude may be used in labour expertise of
      patients exposed to radiation.

PMID- 12524954
TI  - [Several aspects of clinical features of vestibular neuronitis].

PMID- 12524955
TI  - [Use of auditory brain stem implant in a patient with bilateral vestibular
      schwannoma (type 2 neurofibromatosis].
AB  - Surgical technique and functional results of implantation of the acoustic implant
      of the brain stem (BS) are described for a 16-year-old patient with bilateral
      vestibular shvannoma (neurofibromatosis of type 2). Initially, a large (IV
      degree) tumor was removed from the left cerebellopontile angle using the
      translabyrinthine-transcochlear approach. The function of the facial nerve
      recovered completely. The BS implant was implanted a year later in the course of
      removing shvannoma from the right cerebellopontile angle using the above
      approach. The patient received 22-channel implant Nucleus-CI22M. Speech
      intelligibility improved by 90-100%. BS implantation is today the only effective
      method of reestablishment of acoustic sensations in patients with bilateral
      destruction of the acoustic nerves due to bilateral vestibular shvannoma.

PMID- 12524956
TI  - [Incidence of purulent frontal sinusitis in Samara].
AB  - The author analyses incidence of purulent frontal sinusitis in Samara, structure
      of this disease and its social implications by the data from the ENT clinic of
      the Samara State Medical University for 1990-2000.

PMID- 12524957
TI  - [Epidemiological characteristics of acute otitis media in children of Cambodia].
AB  - 1606 children have undergone an otoscopic examination in a children's hospital.
      Maximal incidence of acute otitis media was registered in 1 to 4 year olds and in
      newborns. Acute catarrhal otitis occurred more frequently than acute otitis media
      purulenta in all the age groups.

PMID- 12524958
TI  - [Difficulties of diagnostic and therapeutic policy in association of purulent
      intracranial processes with inflammatory ENT diseases].
AB  - The paper analyses treatment given to 125 patients with purulent intracranial
      processes combining with inflammatory diseases of the paranasal sinuses, ear and
      other diseases. Otorhinogenic genesis was diagnosed in 45.6% cases. Often,
      affections of the paranasal sinuses and ear mask the true reason of the
      intracranial pathology, making problems for diagnosis and choice of therapeutic
      policy. Differential-diagnostic features of the diseases which may complicate
      with purulent intracranial processes as well as urgent therapeutic measures are
      described.

PMID- 12524959
TI  - [Diagnosis and treatment of patients with acute postintubation and post
      tracheostomy stenosis of the larynx and trachea].
AB  - The data on diagnosis and treatment of 200 patients with acute postintubation
      laryngostenosis (LS) and tracheostenosis (TS) are reviewed. Peculiarities of
      tracheostomy technique practiced in critical care units are specified.
      Postintubation and posttracheostomy alterations in the larynx and trachea
      detected endoscopically are described. Effective endosurgical methods are
      proposed to avoid multistage surgical rehabilitation for recovery of the
      respiration function in 97% LS and TS patients.

PMID- 12524960
TI  - [Magneto- laser-phoresis with heparin in the treatment of patients with chronic
      pharyngitis].
AB  - The results of treatment of various forms of chronic pharyngitis by
      magnetolaserophoresis (MLP) with heparin show that MLP is more effective in
      hypertrophic chronic pharyngitis. It is emphasized that when planning treatment
      of chronic pharyngitis one should take into consideration the state of the
      gastrointestinal tract.

PMID- 12524961
TI  - [YAG-Nd laser shunting of the tympanic cavity in patients with exudative otitis
      media].
AB  - A novel method of surgical treatment of exudative otitis media with YAG-Nd laser
      for shunting of the tympanic cavity has been introduced in therapy of 75
      patients. Long-term outcomes of the above treatment characterize it as effective
      and safe in exudative otitis media.

PMID- 12524962
TI  - [Antioxidants and hyperbaric oxygenation in the treatment of sensorineural
      hearing loss in children].
AB  - Efficiency of hyperbaric oxygenation (HBO) in combination with antioxidants was
      studied in 36 children aged 1-14 years with neurosensory hypoacusis vs standard
      treatment. A course of HBO consisted of 10 sessions (1.4 atm) for 40 min. The
      response was registered in 72.2% patients. It manifested in improvement of sound
      perception at 5-25 dB. The highest effectiveness was seen in acute neurosensory
      hypoacusis. Thus, HBO in combination with antioxidants is recommended in combined
      treatment of neurosensory hypoacusis in children.

PMID- 12524963
TI  - [Effectiveness of a new fluoroquinolone antibiotic avelox in the treatment of
      suppurative sinusitis].

PMID- 12524964
TI  - [Curiosine administration for management of wound process after middle ear
      operations in otitis media].
AB  - Curiosine solution was used in surgical treatment of 80 patients with chronic
      otitis media purulenta early after the intervention. Otoscopic, cytological and
      bacteriological examinations have demonstrated that the drug creates
      physiological conditions for activation, migration and division of cells
      participating in tissue regeneration, it promotes bacterial decontamination of
      the wound. Curiosine can be used after radical operations on the middle ear.

PMID- 12524965
TI  - [Use of an acoustics meter in phoniatric practice].

PMID- 12524966
TI  - [Reconstruction of saddle-like nasal deformity with tibial autotransplant].

PMID- 12524967
TI  - [Ceruminoma of the external auditory meatus].

PMID- 12524968
TI  - [Lipomas of the neck].

PMID- 12524969
TI  - [8 cases of laryngeal sarcoma].

PMID- 12524970
TI  - [Malignant histiocytoma of the larynx].

PMID- 12524971
TI  - [Kaposi's sarcoma of the laryngopharynx].

PMID- 12524972
TI  - [A case of tracheal agenesis].

PMID- 12524973
TI  - [Therapeutic and diagnostic policy in acute sinusitis].

PMID- 12524974
TI  - [Therapeutic policy in purulent oto- and rhino-sinusogenic intracranial
      complications].

PMID- 12524975
TI  - [Regional tuberculosis morbidity in the Russian Federation (2000-2001)].

PMID- 12524977
TI  - [Epidemic significance of early detection of patients with tuberculosis].

PMID- 12524976
TI  - [Clinical and social aspects of pulmonary tuberculosis in young women].
AB  - The factors predisposing to tuberculous infection, ways of its detection, and
      specific features of the course were studied in 133 women aged 18 to 30 years.
      The severity of a clinical pattern in the patients and the high rate of detection
      of drug-resistant strains of Mycobacteria tuberculosis were found. The causes of
      untimely and late detection of the disease were clarified. Measures to improve
      the detection of the disease are proposed.

PMID- 12524978
TI  - [Drug resistance of Mycobacterium tuberculosis in the Sverdlovsk Region].
AB  - In the Sverdlovsk Region, multidrug resistance was observed in greater than 8% of
      patients isolating bacteria mainly in the residents of cities, former prisoners,
      those having fibrocavernous tuberculosis complicated by chronic nonspecific lung
      disease (CNLD). Primary resistance was determined in 4.7%, secondary resistance
      developing in 57.4% of cases 3 years or longer after the initiation of treatment.
      The most common cause of multiresistant tuberculosis is irregular treatment,
      patients' discontinuation of some antituberculous agents, as well as scarce
      financing of a tuberculosis control service, which prevents the standard
      treatment regimens from using in tuberculosis. Death due to tuberculosis was
      largely occurred irregularly treated dwellers of cities, tuberculosis-induced
      disabled individuals, alcohol abusers, patients with CNLD, or having
      fibrocavernous tuberculosis resistant to 4-5 antituberculous agents.

PMID- 12524979
TI  - [Influence of the dismissed prisoners with pulmonary tuberculosis on the
      contingents of tuberculosis dispensaries].
AB  - Individuals become annually free from confinement places, among them 10.3-28.6%
      are ill with pulmonary tuberculosis. An average of only 35.6% of this contingent
      are registered at dispensaries in the territories. Their mortality rates within
      the first year of registration are 2.3 times higher than those registered at
      dispensaries of these territories. The authors show it necessary to accomplish
      cooperation between the health care facilities of the Ministry of Health of
      Russia and those of the Ministry of Justice of Russia.

PMID- 12524980
TI  - [Pharmacoeconomic model of the use of rifabutin in new cases of pulmonary
      tuberculosis].
AB  - The formalized procedures to commensurate the results and expenditures were used
      to make a comprehensive evaluation of the clinical efficiency and economical
      expediency of purposeful application of rifabutin in new cases of disseminated
      and destructive pulmonary tuberculosis.

PMID- 12524981
TI  - [Value of autologous blood in the surgical treatment of patients with fibro
      cavernous pulmonary tuberculosis].

PMID- 12524982
TI  - [Problems of epidemiology, diagnosis and treatment of caseous pneumonia].
AB  - In 1992-2001, the growth rates of new cases of caseous pneumonia were 50% greater
      than those of the total new cases of respiratory tuberculosis. Examining the
      specific features of the diagnosis and treatment of 128 new cases of caseous
      pneumonia has identified diagnostic criteria for this form of tuberculosis. The
      leading criteria are X-ray signs of caseous and necrotic lung tissue lesion;
      clinical and laboratory signs of significant endotoxicosis and immunodeficiency.
      The use of extracorporeal immunopharmacotherapy with diucifon in 53 patients and
      the retrosternal injection of isoniazid in combination with hydrocortisone in 43
      patients have shown their efficiencies in the treatment of patients with caseous
      pneumonia.

PMID- 12524983
TI  - [Characteristics of endogenous intoxication of adolescents with tuberculosis].
AB  - The paper shows that there is an association of the pattern of lung lesion with
      the endogenous intoxication in adolescents patients with pulmonary tuberculosis.
      Based on the spectrograms of plasma and the levels of low and medium molecular
      weight substances, the authors revealed clinical features in relation to the
      level of endogenous intoxication and to the values of cellular responses.

PMID- 12524984
TI  - [Diagnostic capacities of laser biophotometry in spinal tuberculosis].
AB  - The capacities of laser biophotometry in the diagnosis of tuberculous spondylitis
      and its complications were studied in 42 patients with this disease and in
      controls. There was a definite significant trend of changes in the reflection
      coefficient of a laser signal in patients with an active inflammatory process in
      the vertebrae, which makes it possible to establish a differential diagnosis of
      the above conditions and to determine the time course of changes in the specific
      process in the vertebral column during therapy. Comparative analysis of the
      proposed method with the thermographic technique used in clinical practice
      demonstrated that the validity of laser biophotometry was highly competitive with
      that of thermography.

PMID- 12524985
TI  - [Spinal and pulmonary tuberculosis].
AB  - The paper presents the results of a study of the clinical course of tuberculous
      spondylitis of combined pulmonary tuberculosis in 86 patients admitted from
      different areas of the Republic of Uzbekistan. Patients with tuberculosis of the
      spine and lung have been shown to have a more unfavourable course of a specific
      process in the bony tissue and lung. The tuberculous process is accompanied by
      severe intoxication, pain syndromes. The severity of the process is aggravated if
      there are extensive suppurative processes around an osseous focus. These patients
      have varying severe cerebrospinal disorders. Moreover, patients with combined
      forms of the process more frequently exhibit concomitant nonspecific visceral
      diseases.

PMID- 12524986
TI  - [A case of tuberculous pericarditis].

PMID- 12524987
TI  - [A case of diagnosis of knee joint ochronosis in bone tuberculosis hospital].
AB  - The author presents a case of knee joint ochronosis or alcaptonuric
      osteoarthrosis, which is rarely encountered in clinical practice. The
      pathogenesis of the disease is attributable to the acculation of homogentisic
      acid derivatives in the body. There is a great similarity of clinical and X-ray
      manifestations of ochronosis and tuberculous arthritis.

PMID- 12524988
TI  - [Diagnosis and treatment of extrapulmonary tuberculosis].

PMID- 12524989
TI  - [Contribution of roentgenology to the development of pulmonology and
      phthisiology].

PMID- 12524990
TI  - [Report of the Minister of Health of the Russian Federation at the Final
      Collegium on March 19-20, 2002 (conclusion)].

PMID- 12524991
TI  - [Frequency of genes speA, speB, and speC in Streptococcus pyogenes strains and
      the identification of the infective agent by polymerase chain reaction].
AB  - In cultures of S. pyogenes isolated from patients and carriers in different
      territories of the Russian Federation the genes of erythorogenic toxins A, B and
      C (speA, speB and specC) were detected. The possibility of the identification of
      S. pyogenes by means of PCR on the basis of primers to erythrogenic toxin B was
      determined. Gene speB was detected in all S. pyogenes cultures under study and
      proved to be species specific. Genes speA and speC were detected, respectively,
      in 29.4% and 9.35% of the S. pyogenes cultures under study. A test system for the
      identification of S. pyogenes on the basis of primers to gene speB was developed.
      The prospects for the detection of genes speA and speC for intraspecific typing
      of this infective agent were evaluated.

PMID- 12524992
TI  - [Hemolytic activity and toxigenicity of Vibrio cholerae of different serogroups].
AB  - Experimental data on the comparative evaluation of the hemolytic activity of ctx+
      Hly- and ctx- Hly+ V. cholerae, serogroups O1 and O139, in the process of their
      cultivation in different nutrient media are presented. The capacity of ctx+ V.
      cholerae of both serogroups cultivated under the conditions of iron deficiency,
      for the production of hemolysin capable of lyzing sheep red blood cells was
      shown. Hemolysin produced by ctx- strains of V. cholerae was synthesized under
      any conditions. The study of hemolysin preparations obtained from ctx- and ctx+
      strains of V. cholerae, serogroups O1 and O139, revealed that they were
      biologically and immunologically similar.

PMID- 12524993
TI  - [Detection of biologically active substances with antagonistic and stimulating
      activity in Spirulina platensis].
AB  - The results of studies on the detection of biologically active substances (BAS)
      in biomass dilutions and culture fluid of Spirulina platensi and algae
      (Chlorella, Fucus, Laminaria) by the agar diffusion method are presented. After
      the sterilization of the solutions with chloroform (CF) a substance with lysozyme
      like activity and 2 substances with antagonistic activity deep in agar and on its
      surface were detected with the use of the micrococcal indicator strain. After CF
      treatment, depending on the concentration of S. platensis strains, a compound
      stimulating the growth of bacteria and sensitive to heat treatment was detected.
      BAS were also detected with the use of other indicator cultures.

PMID- 12524994
TI  - [Morphology and enzyme activity of nonculturable forms of Vibrio cholerae].
AB  - The transition of V. cholerae into the uncultivable state under experimental
      conditions was accompanied by gradual changes in their morphology, motility and
      metabolic activity. The vibrios took the oval form, lost their flagellum,
      motility and enzyme activity on diagnostic media. Dehydrogenase activity tested
      by reduction of triphenyl tetrazolium chloride, increased at the initial stages
      and dropped to the initial level or even lower by the end of the observation
      period (10 months). Similar dynamics was noted when the cytoplasmatic marker
      enzyme--ATPase activity was studied. Glucose catabolism in the uncultivable forms
      shifted towards glycolysis. During 1-2 months ctx and tcp genes could be detected
      in these forms by the PCR. The dynamics of the biological properties under study
      made it possible to find out the existence of 3 functionally different stages in
      the development of an uncultivable population.

PMID- 12524995
TI  - [Epizootic characteristic of rabies today].
AB  - During the 23 year period rabies was registered in the Moscow region in 163 cases
      among foxes, 22 cases among racoon-like dogs, 92 cases among dogs, 54 cases among
      cats. In 1991-2000 ten cases of rabies were registered among other wild animal
      other than foxes and raccoon-like dogs (hares, hedge-hogs, polecats, badgers,
      hamsters, martens, rats). Under today conditions the generalized epizootological
      pattern of rabies is characterized by the vector "natural foci-->anthropurgic
      foci" with wild and domestic animals playing an alternative role in the epizootic
      process and the circulation of the infective agent. Wild carnivorous animals
      maintain natural focal infection in time and space, while all domestic animals
      are a direct or indirect ecological impasse and took no part in the maintenance
      of the infection. Foxes are the main source of infection for the animals of the
      anthropurgic cycle: they play a special role in the development of the epizootic
      situation in the region as the main reservoir and source of the causative agent
      of rabies as a natural focal infection. Among other wild animals, raccoon-like
      dogs are involved into epizootic and epidemic chains. Dogs are the main objects
      to be infected in the anthropurgic cycles, while cats--a progressing group of
      risk. During the period of 25 years a decrease in the probability of natural
      rabies was noted.

PMID- 12524996
TI  - [Sanitary control of the territory: data bases on the spread of some quarantine
      infections].
AB  - The data bases (DB) on the spread of plague, yellow fever and contagious virus
      hemorrhagic fevers (CVHF) in foreign countries have been created. These DB
      contain information on the main international air and sea ports and their
      relationships with natural focal territories. The data base "Sanitary control.
      Yellow fever" contains information on different species serving as vectors for
      yellow fever virus. Information on the circulation of the causative agents of
      Ebola fever, Lassa fever and Marburg disease in African countries has been
      introduced into DB, the differentiation of countries by the degree of the
      potential danger of the CVHF spread has been made.

PMID- 12524997
TI  - [Dynamics of autoantibodies in elderly persons in the process of vaccination with
      Grippol and multicomponent vaccine VP-4].
AB  - The dynamics of antibodies to organ specific and organ nonspecific antigens in
      the process of combined immunization with Grippol, an influenza polymer subunit
      vaccine and polycomponent vaccine VP-4 used for prophylaxis of acute respiratory
      infections, was under study. Persons aged 65 years and older were vaccinated.
      Grippol alone was introduced in a single subcutaneous injection into 92 persons
      and Grippol in combination with vaccine VP-4--to 103 persons. B[symbol: see text]
      4 Vaccine was introduced intranasally and orally (6-8 doses). The administration
      of vaccine VP-4 was started simultaneously with vaccination with Grippol. Prior
      to immunization and 1 and 5 months later autoantibodies to the following antigens
      were detected: DNA (native and denaturated), collagen, elastin, myelin basic
      protein, microsomal fractions of kidneys, lungs, heart, liver, intestine,
      pituitary body, thyroid gland, pancreas, adrenal glands, ovaries, mucous and
      muscular layers of stomach. The number of persons with the level of antibodies at
      least to one of the antigens under study exceeding the normal values prior to
      vaccination varied from 19.4 +/- 8.6% to 41.5 +/- 7.7%, the average values of
      positive sera being 0.26 +/- 0.05 to 0.32 +/- 0.08 delta OD. One and 5 months
      after vaccination both values varied within the same limits in both groups.
      Immunization with Grippol as well as with its combination with vaccine VP-4 was
      found to increased spectrum of antibodies to tissue antigens and their increased
      content. The data give evidence that Grippol and vaccine Vp-4, introduced
      according to the immunization schedule used in these experiments, do not induce
      development of autoimmune processes.

PMID- 12524998
TI  - [Comparative population study of the etiological role of causative agents of
      purulent inflammatory diseases and serum antibodies to antigens of opportunistic
      microorganisms].
AB  - The comparative study of the relationship between the levels of serum antibodies
      to the antigens of opportunistic microorganisms of 5 genera (Pseudomonas,
      Proteus, Staphylococcus, Klebsiella, Escherichia) and the microbial status was
      carried out. A total of 854 patients from 10 profile departments of a surgical
      hospital were examined. Population analysis and statistical methods of processing
      the results of the examination of 353 practically healthy subjects and 268 blood
      and plasma donors permitted the norms for the levels of specific antimicrobial
      antibodies (decreased, normal, elevated levels) were established. The constancy
      coefficients of Pseudomonas, Staphylococcus, Klebsiella, Escherichia and the
      number of patients with elevated titers of specific serum antibodies were found
      to be positively correlated (r = +0.47-0.89, p < 0.01). The data thus obtained
      made it possible to substantiate the importance of population serological
      investigations for the evaluation of the epidemiological situation in the
      surgical hospital.

PMID- 12524999
TI  - [Human immunoregulating (suppressing?) CD4+, CD25+ T lymphocytes ex vivo and in
      vitro, in the normal state and in pathology].
AB  - Among T lymphocytes CD4+, the subpopulation of cells carrying the alpha-chain of
      the receptor of interleukin-2 (CD25) and designated as regulating T cells (Treg)
      has recently been marked out. Such cells produce mainly suppressing effect in the
      immune system and have been identified not only in experimental animals, but also
      in humans. The prolonged experience of the evaluation of such cells has been
      summarized with the cells evaluated in the peripheral blood and in culture, after
      their stimulation in vitro, lymphocytes obtained from healthy persons and
      patients with some diseases leading to the development of immunodeficient states
      (bronchial asthma in the state of exacerbation, newly diagnosed pulmonary
      tuberculosis, chronic pyelonephritis). In all cases an increased circulation of T
      cells CD4+, CD25(4), which may be indicative of their immunosuppressing action
      was found. The correlation between the high level of these cells ex vivo and a
      decrease in the proliferative activity of T cells in vitro is noted. The level
      and functional properties of the subpopulation of T lymphocytes CD4+, CD25+ are
      among the most informative criteria of the functioning of me immune system in the
      normal state and in immunopathology. Search for medicinal preparations modulating
      the function of human regulating T lymphocytes is necessary.

PMID- 12525000
TI  - [Bacterial-fungal associations in the intestine under the conditions of
      colonization by yeast-like fungi of the genus Candida].
AB  - The composition of the fecal microflora in somatic patients and patients with
      enteric infections under the conditions of surpluscolonization by yeast-like
      fungi of the genus Candida was analyzed. The study revealed that the high level
      of fungal contamination was linked with decreased colonization resistance of the
      intestine (deficiency in bifidoflora) and with the presence of opportunistic
      microorganisms: Staphylococcus aureus, hemolytic and lactose-negative Escherichia
      coli, as well as nonfermenting Gram negative bacteria. The antilysozyme activity
      of enterobacteria was found to increase in the course of their joint cultivation
      with fungi of the genus Candida, that may be regarded as one of the mechanisms of
      the formation and maintenance of pathobiocenosis.

PMID- 12525001
TI  - [Specific biological features of opportunistic bacteria determining
      dysbacteriosis in the composition of the large intestine normal microflora].
AB  - Dysbiotic manifestations in the gastrointestinal tract are widely spread. They
      are characterized by a prolonged, persistent course with the tendency to
      transition to the chronic form and poorly respond to corrective treatment. The
      occurrence of high concentrations is 70% for Klebsiella oxytoca, while for K.
      pneumoniae--within the limit of 30%. The most topical problem is colonization of
      the intestinal mucosa in children aged up to 1 year by Klebsiella, the seeded
      bacteria retaining their capacity for growth for up to 2-3 years despite the use
      of probiotics. As shown in this study, the occurrence of Klebsiella and the level
      of the antilysozyme and "antiinterferon" activity of these bacteria, their
      resistance to antimicrobial preparations increase, correlating with the level of
      dysbiotic disturbances.

PMID- 12525002
TI  - [Laboratory diagnostics of infections caused by cytomegalovirus and parvovirus
      B19 in patients with secondary immunodeficiency].
AB  - To improve the quality of diagnostics and treatment of patients with
      immunodeficient states, two groups of patients were examined for the presence of
      cytomegalovirus (CMV) infection, among them 1,348--with clinical manifestations
      of CMV infection (group 1) and 335 hematological patients (group 2); in addition,
      36 patients with secondary immunodeficiency and 31 patients with aplastic and
      hemolytic anemia, or with anemia of unclear origin were examined for the presence
      of parvovirusinfection (B19). The results of enzyme immunoassay, polymerase chain
      reaction and immunofluorescence tests active CMV infection, confirmed by
      determination of IgM, low avidity IgG, antigen and DNAemia, was registered in
      group 2 more often than in group 1. Examinations on the presence of parvovirus
      infection revealed that in anemia patients with the low level of IgG or its
      absence IgM was also detected more often than in group 1. In mixed infection
      caused by CMV and parvovirus B19 the disease took a more severe course than in
      monoinfection, which was probably due to the parallel action exerted by
      parvovirus on erythrocyte production in hematopoiesis and by CMV on the monocytic
      and macrophagal row of cell.

PMID- 12525003
TI  - [Application of different methods in the diagnosis of respiratory mycoplasmosis].
AB  - A complex of methods for the detection of Mycoplasma pneumoniae and Mycoplasma
      hominis in children and adults with respiratory diseases (acute, chronic and
      obstructive bronchitis, pneumonia, recurring croup, bronchial asthma), as well as
      in children frequently having acute respiratory diseases, has been worked out and
      tested. Both infective agents are frequently detected in the above mentioned
      pathological processes as monoinfection or mixed infection. Mycoplasma antigens
      are capable of prolonged (up to 1 year) persistence in the patient body in spite
      of etiotropic therapy and the presence of specific antibodies. The method of the
      preliminary treatment of specimens for the polymerase chain reaction is proposed:
      the specimens are subjected to prolonged deproteinization, which makes it
      possible to detect M. pneumoniae in some cases of chronic infection when it
      cannot be detected by routine methods.

PMID- 12525004
TI  - [Antibiotic properties of Lactobacillus acidophilus, "Narine" strain, and the
      ways for their improvement].
AB  - L. acidophilus strain 317/402 "Narine" shows high antimicrobial activity with
      respect to pathogenic microorganisms. The degree of the activity of lactobacilli
      depends on cultivation conditions and the composition of the culture medium and
      its acidity, age of the culture, conditions of technological process, etc. The
      antimicrobial inhibition concentration of the product "Narine", ensuring in vitro
      activity against Yersinia enterocolitica, Y. pseudotuberculosis, Vibrio NAG,
      etc., has been established.

PMID- 12525005
TI  - [Evaluation of hypoxic state in experimental animals induced by Yersinia pestis
      antigens].
AB  - Some characteristics of purine metabolism in experimental animals (white mice,
      clawed jirds and guinea pigs), injected intraperitoneally with Y. pestis "murine"
      toxin and capsular antigen (Fraction 1), were studied. Under the influence of
      sublethal doses of these antigens increased levels of guanine and xanthine in
      blood were noted. Changes in the content of xanthine oxidase in cells were
      insignificant. In white mice and clawed jirds the activity of succinate
      dehydrogenase decreased under the action of "murine" toxin and increased after
      the injection of Fraction 1.

PMID- 12525006
TI  - [Cultivation of Pseudomonas aeruginosa in media with chlorella fermentative
      hydrolysate as nutrient base].
AB  - The specific features of the growth of P. aeruginosa in media prepared with the
      use of Chlorella fermentative hydrolysate as nutrient basis were studied. The
      accumulation of microbial biomass was shown to depend on increased content of
      amino nitrogen in the media, while the effectiveness of the pyocyanin formation
      was linked with decreased content of amino nitrogen and a rise in the amount of
      sodium chloride.

PMID- 12525008
TI  - [Detection of tissue specific antigen-binding lymphocytes in patients with acute
      enteric infections].
AB  - A total of 88 patients with salmonellosis, acute dysentery, alimentary
      toxicoinfection, acute gastroenterocolitis were examined. The study was aimed at
      early determination of the involvement of organs and tissues into the
      inflammatory process and detection of antigen-binding lymphocytes with the use of
      erythrocytic immunoreagents prepared from tissue antigens of mucous membranes of
      small and large intestine, duodenum, stomach, gall bladder, as well as liver and
      pancreas. The study demonstrated that as early as on day 1-3 of the disease the
      development of the inflammatory process in different organs was accompanied by
      the appearance of the corresponding tissue specific (organ specific) antigen
      binding lymphocytes in all patients. As a rule, patients with different acute
      enteric diseases significantly differed by the frequency and spectrum of the
      involvement of such organs and tissues into pathological process.

PMID- 12525007
TI  - [Autoantibodies to thyroid gland antigens in chronic relapsing urticaria].
AB  - The content of total IgE, antibodies to thyroglobulin (TG-Ab), antibodies to
      thyreoid peroxidase (TPO-Ab) in the blood serum and skin reaction to autologous
      serum were detected in patients with chronic relapsing urticaria (CRU). The skin
      test to autologous serum yielded positive results in 42% of the patients. The
      elevated levels of TG-Ab and TPO-Ab were detected in 30.7% and 35.4% of the
      patients, the elevated level of total IgE was detected in 60% of the patients. At
      the same time the detection rates of antithyreoid antibodies and the elevated
      level of IgE were not linked with skin reaction to autologous serum. Apparently,
      in addition to autoantibodies to IgE or its receptor (the positive skin test to
      autologous serum), thyroid gland antibodies may take part in the mechanism of the
      CRU formation.

PMID- 12525009
TI  - [Interferon in patients with hemorrhagic fever with renal syndrome].
AB  - The in vitro production of alpha- and gamma-interferon (IF) by peripheral blood
      lymphocytes (PBL) and the concentration of serum IF in 50 patients having
      hemorrhagic fever with renal syndrome (HFRS), as well as the possibility of the
      formation of spontaneous IF by PBL and the influence of the patient blood plasma
      on alpha-IF genesis, was studied. The development of HFRS was accompanied by a
      rise in the level of serum IF with different speed, depending on the severity of
      the disease with simultaneous suppression of the lymphocytes capacity for alpha-
      and especially gamma-IF production. In cases of moderate and severe forms of the
      disease no restoration of the IF system occurred by the moment of discharge from
      the hospital. In a few patients spontaneous IF in low titers was determined. In
      cases of the moderate form of the disease in the oligoanuretic period and the
      severe form of the disease in the oligoanuretic and polyuretic periods the
      patients' blood plasma essentially suppressed the production of alpha-IF by PBL.

PMID- 12525010
TI  - [Antibodies to cytokeratin-8 in patients with different lung pathology].
AB  - Antibodies to cytokeratin-8 were detected by enzyme immunoassay (EIA) in sera of
      135 patients with cryptogenic fibrosing alveiolitis, different rheumatic
      diseases, sarcoidosis and exogenous allergic alveolitis, 109 patients with
      inflammatory lung diseases and 74 donors of the Moscow Blood Transfusion Station.
      The results revealed that The frequency of positive EIA reactions among the
      donors was 7%, while in the group of patients with rheumatic diseases--from 5.9%
      (scleroderma) to 42.9% (fibrosing alveolitis). Positive reactions also occurred
      in patients with exogenous allergic alveolitis and sarcoidosis. In the group of
      patients with chronic inflammatory lung diseases, i.e. in pathologies of non
      autoimmune origin, positive reactions occurred in 13.3-33.3% of cases. To improve
      diagnostics and to disclose the mechanisms of pathogenesis, more detailed study
      of anticytokeratin antibodies in cases of interstitial lesions and chronic
      inflammatory lung diseases are necessary.

PMID- 12525011
TI  - [Prevalence and structure of acute respiratory virus infections].
AB  - Information on epidemiology of acute respiratory virus infections (ARVI) is
      reviewed and analyzed. In addition to influenza viruses, the role of respiratory
      syncytial viruses (RSV), rhino- and adenoviruses, as well as other viruses, in
      the development of respiratory diseases, especially in newborns, young children
      and elderly persons, is emphasized. A high proportion of RSV in the etiology the
      severe forms of ARVI and in the development of intrauterine infection is pointed
      out. The conclusion has been made that the identification of the causative agents
      of ARVI with the use of modern methods makes it possible to determine the real
      role of each of the pathogens in the formation of the severe forms of diseases,
      as well as the expediency of vaccinal prophylaxis.

PMID- 12525012
TI  - [Types of secretion and regulation of the functional activity of molecules
      associated with the pathogenicity of Enterobacteriaceae].
AB  - Five types of nonhomologous systems of the export of protein molecules, known to
      exist in pathogenic bacteria, are characterized. The described secretion systems
      take part in the synthesis of not only toxic proteins, but also different
      adhesins and hydrolytic enzymes. In the export of Enterobacteriaceae toxins
      secretion types I, II, III and V are of importance. Characteristics of Sec
      dependence at the stage of transport through the cytoplasmic membrane is the key
      sign in their differentiation. The functional activity of bacterial toxins and
      the level of toxigenicity expression are finely regulated signs, mediated by
      external signals. The systems for their regulation are relatively few in number
      and rather conservative. As shown in this study, the regulation of pathogenicity
      expression has no specific mechanisms. Moreover, it is regulated by common
      systems and mechanisms for the regulation of usual physiological processes.

PMID- 12525013
TI  - [Common stressor proteins in bacteria].
AB  - Research data on common stressor proteins of bacteria obtained during recent 10
      years are updated and analyzed. Bacteria of one and the same species were shown
      to give similar response to the action of different stressors; the main stressor
      proteins of different bacteria appeared to be homologous; bacteria have cross
      protection from different stressors. In addition, some common stressor proteins
      of bacteria were found to be homologous with human antigens that is of great
      importance for immunobiotechnology.

PMID- 12525014
TI  - [Characteristics of microorganisms colonizing human intestine].
AB  - Introduction of novel methods of microbial diagnostics has considerably broadened
      our conceptions on the qualitative and quantitative variety of microorganisms
      inhabiting human gastrointestinal tract. In this review morphological and
      functional properties of obligate anaerobic bacteria (bifidobacteria,
      lactobacilli, eubacteria, peptostreptococci, clostridia, bacteroids,
      fusobacteria) and facultative anaerobic microorganisms (enterobacteria,
      staphylococci, streptococci, yeast-like fungi of the genus Candida) capable of
      colonizing human intestine are briefly characterized.

PMID- 12525015
TI  - [Possible mechanisms of the reciprocal influence of infections caused by HIV and
      hepatitis C virus].
AB  - Literature data on the pathogenesis of mixed infection caused by human
      immunodeficiency viruses (HIV), type I, and hepatitis C virus (HCV), as well as
      on possible mechanisms of the reciprocal influence of these viruses necessary to
      understand their co-existence, are reviewed. The extrahepatic replication of HCV,
      its role in the infectious process and its possible contribution to the course of
      mono- and co-infection are considered in detail. Much attention is paid to the
      specific features of immune response in HIV-HCV infection and the immunomediated
      mechanisms of the reciprocal influence of the viruses. The problem of the
      hepatotoxicity of antiretrovirus preparations, actively discussed in literature,
      is considered from biological positions. The role of the phenomenon of immunity
      reconstitution in cases of the exacerbation of chronic HCV infection in the
      course of the treatment of HIV infection as well as of other factors, in
      particular, infections caused by other parenterally transmitted viruses, in the
      course of HIV-HCV co-infection is pointed out.

PMID- 12525016
TI  - [Filovirus haemorrhagic fevers: Ebola fever].
AB  - Epidemiological issues, clinical course and laboratory diagnostics of Ebola
      haemorrhagic fever are reviewed. The structural features of virions and genetic
      variants of the virus are described along with ecology of Ebola virus. The data
      on Ebola fever global morbidity are also presented.

PMID- 12525017
TI  - [Innovative approaches to teaching medical microbiology to the students].

PMID- 12525018
TI  - [Clinical, multicentric, and open study to evaluate the efficacy of and tolerance
      to sildenafil in patients with erectile dysfunction].
AB  - Erectile dysfunction (ED), defined by the Impotence-NIH Consensus Conference as
      the "persistent inability to achieve and/or maintain erection sufficient for
      satisfactory sexual activity" affect more than 100 million men worldwide, at
      particular severity levels. The global prevalence of ED is estimated to affect
      about 10%, but has been found to increase significantly with age (39% in men 40
      years of age and 67% at 70 years of age). In men aged 40 to 70 years, the severe
      ED prevalence increased of three folds, 5 to 15%. In order to evaluate the
      efficacy and tolerance of sildenafil, it was conducted a national open,
      multicentre study on a portuguese population affected by ED. Subjects under
      ambulatory treatment were recruited in Psychiatry/Sexology Clinical units and
      Urology/Andrology. The results of the study carried out on a group of 62 men with
      ED, demonstrate that sildenafil was effective in the recovering of erectile
      function, increasing the number of attempts to sexual activity and improving
      their success rates (mainly in severe dysfunction). Fifty one patients treated
      with sildenafil, at the end of the study referred a global improvement in their
      erections (92.2%). Doses of 50 mg and 100 mg sildenafil were used and were well
      tolerated and also effective in the treatment of this pathology (70% and 69%
      respectively). Being this study a flexible dose one and taking into consideration
      that the final dose used was found the more suitable to the patients, can be
      concluded that 43.1% of the patients elected dose of 50 mg whereas 56.9% elected
      the maximum prescribed dose of 100 mg. Over and above global efficacy
      experimented by patients, a significant improvement in the sexual activity with
      partners was occurred. These results make possible a final conclusion--in the
      studied patients group affected by Erectile Dysfunction, aside from associated
      somatic pathology, sildenafil use provided a remarkable clinical profit, in what
      concerns global efficacy, by erectile function mechanisms improvement, concerning
      patients sensitivity of improvement, occurring in the major part of them, being
      these of high importance to the lifting up of their self-esteem.

PMID- 12525019
TI  - [Child abuse in the family].
AB  - The objective of this study is to carry out a current survey of the situation of
      child abuse in the family. It is based on a national survey conducted in 1996,
      which was addressed to childcare professionals (in the areas of health, education
      and social services). This survey was based, on the one hand, on a wide-ranging
      definition of child abuse, including within it not just active forms of physical
      and psychic violence against the child, but also forms of (both material and
      affective) privation, omission or negligence which affect the child's growth and
      development. On the other hand, this study also favoured a contextual approach to
      child abuse. 1,126 institutions in Portugal were contacted and 755 valid survey
      responses were received. This report outlines some of the results obtained,
      namely by providing a description of the sample of the 755 child abuse victims,
      the respective social and family contexts to which they and the aggressors
      belong, as well as the types of abuse which have been committed against them; and
      a typology of forms of abuse and negligence, describing not just the internal
      aspects that make up child abuse directly, but also its relationship to the
      child's social and family contexts of belonging. The typology was derived from
      the statistical handling of the data gathered (factorial analysis of multiple
      matches, followed by a hierarchical analysis into clusters). A number of key
      concepts are summarised in the conclusion. Children of all age groups and of both
      sexes, and from all types of families and social backgrounds, regardless of their
      place in the phratry, are subject to abuse in Portugal. But different types of
      abuse and negligence are associated with the contexts to which the children and
      their families belong. Healthcare professionals are irreplaceable when it comes
      to detecting the wide variety of types of child abuse, and are an essential look
      out post for two types of abuse which often slip through the net of other
      professionals: abuse of the embryo, foetus or new-born child, and sexual abuse.
      In Portugal the existence of various forms of poverty (whether in material or
      educational terms), and the lack of family support services and mechanisms, are
      of particular significance. And tied in with this structural aspect there is the
      significant factor of alcoholism, which in the sample under investigation is
      statistically much more significant than drug addiction.

PMID- 12525020
TI  - [Release of cytochrome C with the interaction of bilirubin, amyloid beta-peptide
      and glycochenodeoxycholate from isolated mitochondria].
AB  - The pathogenesis of cholestasis, bilirubin encephalopathy, and Alzheimer's
      disease appears to result from accumulation of diverse cytotoxic agents, which in
      turn may cause apoptotic cell death. In addition, mitochondria has lately been
      considered as a central executioner of programmed cell death, through the release
      of caspase activating factors. The aims of this study were to: (a) investigate
      mitochondrial perturbation during incubation of isolated mitochondria with
      unconjugated bilirubin (Bb), amyloid beta-peptide (A beta), and
      glycochenodeoxycholate (GCDC); (b) characterize membrane perturbation in isolated
      mitochondria induced by each toxic agent, and determine whether the mitochondrial
      permeabilization is required for cytochrome c redistribution. Mitochondria were
      isolated from rat liver and brain. Swelling and cytochrome c release were
      evaluated by spectrophotometry and western blot, respectively. The results showed
      that Bb as well as A beta and GCDC act directly at the mitochondrial level
      causing increased organelle volume, permeabilization, as well as cytochrome c
      release from the intermembrane space in a dose-dependent manner (P < 0.01).
      Moreover, cyclosporine A inhibited mitochondrial permeability, particularly after
      Bb- and GCDC-induced swelling (P < 0.01). Cytochrome c efflux was invariably
      prevented by cyclosporine A (P < 0.05). In conclusion, the results indicate that
      Bb-, A beta-, and GCDC-induced toxicity, culminating in apoptosis, may result
      from enhanced mitochondrial permeability, followed by cytochrome c efflux, which
      can be explained at least in part by the megapore opening.

PMID- 12525021
TI  - [Cardiovascular risk factors -- from the mathematical formula to clinical
      practice].
AB  - In the last decade's cardiovascular risk factors evaluation and identification
      have been priority issues. In the 90's, the Second Joint European Task Force
      developed a chart for the evaluation of a 10 years coronary risk. The chart is
      based on sex, age, diabetes presence, systolic blood pressure, total cholesterol
      and smoking habits. Since then, this chart has been currently used both in
      clinical practice and in clinical trials. A closer evaluation of the chart shows
      that some factors could silence the global action of the other factors. These
      major factors assume a prevailing role in global coronary risk results, having
      direct implications in clinical decisions and limiting the population's
      definition in clinical trials, based in chart results.

PMID- 12525022
TI  - [Leptin].
AB  - Leptin is a product of the ob gene. It is syntetized by the adipocytes. This
      review will summarize the current findings of the physiopathology and actions of
      leptin.

PMID- 12525023
TI  - [Apoptosis and human reproduction].
AB  - Apoptosis is a common form of physiological cell death that is essential to
      maintain homeostasis in human tissues and when deregulated, explains the
      physiopathological events in most diseases. This is true both in the ovary and
      uterus, two essential organs for human reproduction. The correct understanding of
      the role that this phenomenon carry out to regulate ovarian and uterine cellular
      populations and consequently to regulate reproductive physiology, might allow in
      the future the development of new strategies to treat infertility. This paper is
      a review of the current understandings about apoptosis and its involvement in
      human reproductive physiology.

PMID- 12525024
TI  - [Human immunodeficiency virus infection. Dermatologic perspective].
AB  - High prevalence and atypical cutaneous symptoms, signals and evolution are main
      characteristics of HIV-associated dermatosis, where infections and neoplasms are
      quite common. Mostly difficult, diagnosis of skin involvement is important to
      corroborate the clinical suspicion of HIV infection. In the present work, after a
      short review on epidemiology, pathogeny and clinical aspects of the HIV
      infection, main AIDS-related dermatosis are described. The usual clinical
      patterns and their modifications are reviewed.

PMID- 12525025
TI  - [Acute thyroiditis].
AB  - We review the pathophysiology, clinical features and therapy of acute
      thyroiditis. Four cases are reported stressing the role of fine needle aspiration
      for the diagnosis of this clinical entity.

PMID- 12525026
TI  - [Corticoid resistant nephrotic syndrome].
AB  - The authors present a case report on a eighteenth months old male white, who was
      admitted at the Nephrology Unit with nephrotic syndrome--first episode.
      Considering the age of the patient, the laboratorial results and the negative
      result of the immunologic study, the first diagnostic hypothesis was the minimal
      lesions nephrotic syndrome and was initiated treatment with corticosteroid in the
      dosis of 60 mg per square meter, per day. The generalized oedema and the massive
      proteinuria persisted although the corticosteroid and additional therapy. At the
      sixth week the renal biopsy revealed membranous glomerulonephropathy with
      mesangial deposits of IgG, IgA, IgM, C3, C4, C1q, compatible with an immunologic
      disease and suggestive of lupus nephritis. Then, was initiated the therapeutic
      protocol with 6 menstrual pulses of intravenous cyclophosphmide. After the 4th
      pulse of cyclophosphamide the proteinuria was negative, and the patient remains
      in clinical and laboratorial remission since the end of the 6 pulses, and after
      14 months of follow-up.

PMID- 12525027
TI  - [Glioblastoma multiforme... with multifocal presentation].
AB  - Glioblastoma multiforme is the most common malignant primary brain tumor in
      adults (+/- 40% of the Central Nervous System primary tumors). Representing only
      2% of all oncologic processes, they are associated with a great deterioration of
      cerebral functions and a poor prognosis, facts that contribute to their great
      individual and social impact. The authors report a case of glioblastoma
      multiforme, with multifocal lesions "ab initio" and show the difficulty to make a
      correct diagnosis, even with the most modern imagiologic techniques. They also
      make a brief review of the literature.

PMID- 12525028
TI  - [Depression caused by an anti-acne agent].
AB  - The present clinical case reports an adolescent with depression, strongly
      correlated with the adverse reactions of isotretinoin.

PMID- 12525029
TI  - [Letter on the article published in the Acta Med Port 2001; 14:395-398].

PMID- 12525030
TI  - [Research progresses in the chemistry and pharmacology of Angelica sinensis
      (Oliv.) Diel].

PMID- 12525032
TI  - [Contents of ten trace elements in Epimedium acuminatum Franch. and its different
      processed products].
AB  - OBJECTIVE: Determine and compare the contents of ten trace elements in crude E.
      acuminatum and its three different processed products. METHOD: Using flame atomic
      absorption spectrometry. RESULT: The ten trace elements were found in both the
      crude drug and its three processed products, and in terms of contents some of the
      trace elements in all the three processed products are higher than those in the
      crude drug. CONCLUSION: According to the trace element contents, the three
      processed products of E. acuminatum have their own advantages. It is thus
      suggested that thoroughgoing clinical and experimental researches be performed
      anew for the long-shelved processing methods.

PMID- 12525031
TI  - [A preliminary study on relationship between Atractylodes lancea and A. chinensis
      as analyzed by RAPD].
AB  - OBJECTIVE: To study the relationship between A. lancea and A. chinensis by RAPD
      analysis. METHOD: Using 10 random primers, RAPD of seven Atractylodes samples was
      performed. The result was analyzed by RAPDistance Package Version 1.04. RESULT: A
      total of 60 polymerphic loci were amplified. It appears that the Atractylodes
      samples tend to cluster in relation to their habitats, and A. lancea has close
      phylogenetic relationship with A. japonica. CONCLUSION: A certain correlation
      among the chemical composition, genetic diversity and geographic distribution has
      been revealed. It is reasonable to separate A. lancea from A. chinensis according
      to their habitats.

PMID- 12525033
TI  - [Genetic transformation of hairy roots in Trichosanthes kirilowii Maxim. by Ti
      and Ri plasmids].
AB  - OBJECTIVE: To establish a hairy root culture system by double transformation for
      Trichosanthes kirilowii. METHOD: 1. Crown galls were induced by direct infection
      of sterile seedlings of T. kirilonii with Agrobacterium tumefaciens C58, and then
      the hairy roots were obtained from the regenerated plants by infection with A.
      rhzogenes 15834; 2. Transformation of Ti and Ri plasmids was inspected by high
      pressure-paper electrophoresis; 3. The protein contents in the tissues of T.
      kirilowii were inspected by spectrophotometer and SDS-PAGE. RESULT: A hairy root
      culture system has been established successfully by double transformation with Ti
      and Ri plasmids in T. kirilowii. CONCLUSION: Compared with the ordinary hairy
      roots, the double transformed hairy roots grow faster but retain similar protein
      contents.

PMID- 12525034
TI  - [Study on the preparation of baicalin complex with phospholipid].
AB  - OBJECTIVE: To choose the optimization conditions for the formation of baicalin
      complex with phospholipid. METHOD: A reasonable criterion of accurate evaluation
      was established, by which such factors as temperature, the ratio of baicalin to
      phospholipid and the concentration of reactants were examined and the
      orthographic design was used. RESULT: The best conditions were obtained through
      statistical analysis and proof test. CONCLUSION: The formation of baicalin
      complex with phospholipid was greatly influenced by the solvent, concentration
      and reactant ratio.

PMID- 12525035
TI  - [Study on improving the dissolution rate of tanshinone in vitro by solvent
      deposition method].
AB  - OBJECTIVE: To improve the dissolution rate of a poorly watersoluble drug,
      tanshinone. METHOD: Using pregeletinged starch as carrier, to prepare solvent
      deposition systems of tanshinone solvent method. The dissolution rate of
      tanshinone, solvent deposition systems and physical mixture were detected, and
      the physico-chemical properties of these study forms were investigated with
      scanning electron microscopy and infrared spectroscopy. RESULT: The dissolution
      rate of tanshinone from the solvent deposition systems in vitro was significantly
      higher than that from physical mixtures and tanshinone powered alone. Tanshinone
      deposited on the surface of the carrier in crystal form, and the size was
      obviously reduced. A lot of acerose crystals of tanshinone on the surface of the
      carrier occurred. No chemical reaction acted between tanshinone and carrier.
      CONCLUSION: The dissolution rate of tanshinone in vitro can be improved with
      solvent deposition method.

PMID- 12525036
TI  - [Studies on chemical constituents from the herb of Peucedanum decursivum (Miq.)
      Maxim].
AB  - OBJECTIVE: To investigate the chemical constituents of Peucedanum decursivum
      commonly used in traditional Chinese medicine. METHOD: Compounds were separated
      by solvent extraction and column chromatography with silica gel and structures
      were elucidated by chemical evidence and spectral analysis. RESULT: Seven
      compounds were identified as imperatorin, deltoin, columbianadin, beta
      sitosterol, scopoletin, (+)-trans-decursidinol and daucosterol. CONCLUSION: All
      the compounds were isolated from the plant for the first time.

PMID- 12525037
TI  - [Studies on chemical constituents from Euphorbia fischeriana Steud].
AB  - OBJECTIVE: To study the chemical constituents of ethanol extract from dried roots
      of Euphorbia fischeriana. METHOD: Compounds were separated by column
      chromatography with silca gel and elucidated by chemical evidence and spectral
      analysis. RESULT: Isobauerenyl acetate, beta-amyrin acetate, 24
      methylenecycloartenone,octacosyl ferulate and 2,4-dihydroxy-6-methoxy-3-methyl
      acetophenone were isolated and elucidated. CONCLUSION: All the compounds were
      isolated from the plant for the first time.

PMID- 12525039
TI  - [Studies on quality specification standards for Saposhnicovia divaricata (Turcz.)
      Schischk].
AB  - OBJECTIVE: To work out a qualitative-quantitative standard for Saposhnikovia
      divaricata. METHOD: TLC and HPLC were adopted. RESULT: Four chromone compounds
      were identified by TLC, and the contents of two chromone compounds were
      determined by HPLC. CONCLUSION: Prim-O-glucosylcimifugin, 4'-O-beta-D-glucosyl-5
      O-methylvisamminol, sec-O-glucosylhamaudol and cimifugin should be present
      simultaneously in S. divaricata. The contents of prim-O-glucosylcimifugin and 4'
      O-beta-D-glucosyl-5-O-methylvisamminol in S. divaricata should not be lower than
      0.12% respectively.

PMID- 12525038
TI  - [GC-MS analysis of essential oils from rhizomes of Atractylodes lancea (Thunb.)
      DC. and A. chinensis (DC.) Koidz].
AB  - OBJECTIVE: To analyze the constituents from the rhizomes of Atractylodes lancea
      and A. chinensis in essential oils. METHOD: GC-MS method was used. RESULT: 32 and
      29 compounds were identified respectively. CONCLUSION: The main constituents in
      the essential oils from the rhizome of A. chinensis are beta-eudesmol or a
      mixture of beta-eudesmol and atractylone, whereas from that of A. lancea are
      hinesol, a mixture of beta-eudesmol and atractylone, and atractylone.

PMID- 12525040
TI  - [Research on the transformation of ginsenoside Rg1 by intestinal flora].
AB  - OBJECTIVE: The decomposition of Ginsenoside Rg1(Rg1) by intestinal bacteria in
      rats or human was investigated both in vitro and in vivo. METHOD: The
      decompositions were investigated by means of thin-layer chromatography and
      Electron spurt ion mass. RESULT: It was found that Rg1 was converted into two
      metabolites [Rh1 and 20(S)-protopanaxatriol(20S-Ppt)] by human intestinal
      bacteria in vitro, while three compounds [Rh1, F1, and 20(S)-Ppt] were detected
      in rat intestinal bacteria metabolism in vitro and in vivo. CONCLUSION: The
      decomposition and/or metabolism of Rg1 in rat and human digestive tract was
      confirmed. The mode of metabolism in rat is Rg1-->Rh1(F1)-->Ppt, while in human
      it is Rg1-->Rh1-->Ppt.

PMID- 12525041
TI  - [Influence of oral administration of realgar on contents of copper, zinc and
      selenium in rat tissues].
AB  - OBJECTIVE: To investigate the changes of copper, zinc and selenium levels in rat
      tissues after long-term oral administration of Realgar. METHODS: Rats were given
      Realgar with dosage of 50, 150, 450 mg.kg-1.d-1 for 5 weeks, and the
      concentrations of copper, zinc and selenium in different rat tissues as well as
      the contents of metallothionein in rat liver and kidney were determined with
      atomic absorption and hydride generation-atomic fluorescent technique. The total
      amount of copper excreted from feces and urine of each rat 5 days before the rat
      was killed was also measured. RESULTS: No significant changes of levels of
      copper, zinc and selenium in rat tissues were found after administration of low
      and middle dosages of Realgar. But higher dosage (450 mg.kg-1.d-1) of Realgar
      administration could induce a small but significant decrease of zinc
      concentration in hearts and a increase of copper contents in spleen and tibia, as
      well as twice more copper concentration of kidney. CONCLUSION: Copper deposit in
      kidney was the most significant change found among the trace elements levels in
      rat tissues, and this might be one of the mechanisms for kidney toxicity of
      Realgar.

PMID- 12525042
TI  - [Study on anticancer activity of Syngnathus in vitro].
AB  - OBJECTIVE: To study the anticancer activity of Syngnathus in vitro. METHOD:
      Observing the influence of different extracts from Syngnathus on growth of
      different cancer cell strains by MTT method. RESULT: It has been found out that
      the fat-soluble nonsaponified extract from Temminck et Schlegel and the alcoholic
      extract from Syngnathus acus have cytotoxic activities. The nonsaponified extract
      from Temminck et Schlegel can inhibit the growth of cancer cell strains KB, Hela,
      PAA, K562, and Bcap37, and the alcoholic extract from Syngnathus acus can inhibit
      the growth of cancer cell strin KB, But Bloch shows no apparent anticancer
      activity. CONCLUSION: Syngnathus has promising prospects as an anticancer Chinese
      medicine.

PMID- 12525043
TI  - [Screening of anti-bacteria activity of extracts of Gaultheria leucocarpa var.
      yunnanensis].
AB  - OBJECTIVE: To further develop Gaultheria leucocarpa var. yunnanensis, anti
      bacteria constituents in it were screened. METHOD: The constituents were
      extracted by chromatographic process. The anti-bacteria test was made with
      regulatory method of analysis. RESULT AND CONCLUSION: Anti-bacteria test with
      extracts of water, acetic ester and n-butanol showed that 3 extracts from 22
      samples had anti-Staphylococcus aureus action, and the extracts from root and
      stem showed the same result. 2 extracts could kill Escherichia coli and
      Pseudomonas aeruginosa. The lower the concentrate, the less the anti-bacteria
      action was. These results suggested that not only essential oil but other
      ingredients from G. leucocarpa var.yunnanensis have anti-bacteria activity. Anti
      fungi test of the same extracts didn't indicate remarkable action.

PMID- 12525044
TI  - [Pollen morphology of bee plants in Changbai Mountain area].
AB  - OBJECTIVE: To develop and utilize the bee plants and bee products in Changbai
      Mountain area, the representative area of alpine plants in northeast China
      featuring abundant resources of bee plants. METHOD: The pollen of bee plants was
      observed and studied by LM and SEM. RESULT: The pollen is morphologically oblate,
      suboblate, spheroidal and prolate. The external sculpture is commonly reticulate,
      striate and echinulate. CONCLUSION: Plant pollen identification criteria have
      been furnished for the development of bee plant resources as well as the
      inspection of bee products in Changbai Mountain area.

PMID- 12525045
TI  - [Study on growth rhythm in populations of Pinellia ternata (Thunb.) Breit].
AB  - OBJECTIVE: To study the genetic diversity of Pinellia ternata. the growth rhythm.
      METHOD: Sixteen populations of P. ternata. originated mostly from middle and
      lower reaches of Yangtze River valley were collected and cultivated in Weigang
      Experimental Farm of Nanjing Agricultural University with same cultural
      conditions, whose differences in growth rhythm have been observed and compared
      continuously for two years. RESULT AND CONCLUSION: There are obvious differences
      in sprouting, lamina spreading, bolting and "sprout tumble", Three times of
      "sprouting" and so-called "sprout tumble" and two fast-growing periods for plants
      in most of the populations in spring and autumn respectively were observed within
      a year, including mass bolting in May. But the starting time and duration are
      very different from population to population, with flowering being prior to
      sprouting in the population originated from Jurong county.

PMID- 12525046
TI  - [Preliminary studies on process and ultramicro-pulverization on pharmacodynamics
      of Leech].
AB  - OBJECTIVE: To compare pharmacodynamics of decoction and powder of Leech; To
      identify effect of pharmacodynamics of Leech with new methods of process and
      ultrmicro-pulverization. METHOD: The size of ultramicor-powder of Leech and new
      method processed Leech is determined by BT-1500 size distributive instrument. It
      is compared that the pharmacodynamics of Leech decoction and powder as well as
      ultramicro-powder with new method processed of 1/2 decoction dose by
      anticoagulation and antithrombus action of mice. The safety of different samples
      is identified. RESULT: The pharmacodynamics of samples is as ultramicro-powder of
      Leech with new method processed > ultrmicro-powder of Leech > powder of Leech >
      decoction of Leech. CONCLUSION: The ultramicro-powder of Leech with new method
      processed has better pharmacodynamic effect and the smell of Leech is improved.

PMID- 12525047
TI  - [Effects of different processing products of Cortex Phellodendri on scavenging
      oxygen free radicals and anti-lipid peroxidation].
AB  - OBJECTIVE: To investigate the effects of different processing products of Cortex
      Phellodendri on scavenging oxygen free radicals and anti-lipid peroxidation.
      METHOD: The oxygen free radicals generation system and mouse liver homogenate
      lipid peroxidation in vitro were used. RESULT: The aqueous and 80% alcohol
      extracts of raw, stir-fried, stir-fried with salt, stir-fried with yellow alcohol
      products of Cortex Phellodendri could scavenge superoxide radical(O2-.) generated
      through hypoxanthine-oxidase system and(.OH) generated through Fenton action, and
      inhibit lipid peroxidation induced by hydroxyl radical generation system,
      respectively. But the carbonized product has no effect. There are differences
      among these processed products. CONCLUSION: 80% alcohol extract of stir-fried
      with yellow alcohol products of Cortex Phellodendri was more intense.

PMID- 12525048
TI  - [Studies on chemical constituents in root of Rumex patientia L].
AB  - OBJECTIVE: Investigating the chemical constituents in the root of Rumex
      patientia. METHOD: Compounds were separated by rechromatography on silica gel.
      Their structures were determined by spectral analysis and chemical evidence.
      RESULT: Eight compounds were isolated and identified as 5-methoxy-7-hydroxy-1
      (3H)-benzofuranone (I), 5, 7-dihydroxy-1 (3H)-benzofuranone(II), nonadecanoic
      acid-2,3-dihydroxypropyl ester(III), torachrysone-8-O-beta-D-glucopyranoside(IV),
      gallic acid(V), beta-sitosterol(VI), beta-sitosterol-3-O-beta-D
      glucopyranoside(VII) and catechin(VIII). CONCLUSION: Compound III is a new
      natural products, and compounds I and II were obtained from this plant for the
      first time.

PMID- 12525049
TI  - [Organic acid constituents from the stem of Securidaca inappendiculata Hassk].
AB  - OBJECTIVE: To investigate the organic acid constituents from the stem of
      Securidaca inappendiculata. METHOD: Column chromatographic techniques were used
      to isolate and purify the constituents. The structures were elucidated by spectra
      analysis. RESULT: Five compounds were isolated and identified as ferulic acid
      (I), cinnamic acid(II), palmitic acid(III), salicylic acid(IV) and benzoic
      acid(V). CONCLUSION: Compounds I-IV were isolated from the plant for the first
      time.

PMID- 12525050
TI  - [Studies on chemical constitutents from Penthorum chinense Pursh].
AB  - OBJECTIVE: To study the chemical constituents of Penthorum chinense. METHOD:
      Silica gel and macroporous resin were used as adsorbent for isolation and
      purification. The chemical structures were elucidated by spectral analysis and
      chemical methods. RESULT: Three compounds were isolated from the water-extract of
      P. chinense. The structures were identified as 5-hydroxy-flavanone-7-O-beta-D
      glucoside (I), 2,4,6-trihydroxybenzoic acid (II) and quercetin(III),
      respectively. CONCLUSION: Compounds I and II were isolated from this plant for
      the first time.

PMID- 12525051
TI  - [Chemical constituents in volatile oil from fruits of Alpinia oxyphylla Miq].
AB  - OBJECTIVE: To study the chemical constituents in the volatile oil from fruits of
      Alpinia oxyphylla. METHOD: Using GC-MS to identify the constituents. RESULT AND
      CONCLUSION: Sixty-four compounds were identified on the basis of GC-MS, the main
      ones being p-cymene, valence, linalool, myrtenal, alpha-pinene, beta-pinene,
      furopelargone A and terpinen-4-ol. Three sesquiterpenes valencene, nootkanone and
      nootkanol have been isolated from the CHCl3 extract as check, of these 64
      identified compounds linalyl oxide, valencene, bakkenolide A, furopelargone A and
      3-hydroxycalamenene are reported for the first time.

PMID- 12525052
TI  - [Lipid chemical constituents of Salvia sochifolia C. Y. Wu].
AB  - OBJECTIVE: To study the lipid chemical constituents of Salvia sochifolia growing
      in Yunnan province. METHOD: Chromatographic techniques were used to isolate the
      compounds and the structures were identified by spectral analysis. RESULT: Five
      compounds were isolated from the plant and identified as 2 alpha, 3 alpha
      dihydroxyurs-12-en-28-oic acid, 2 alpha, 3 alpha, 24-trihydroxyurs-12-en-28-oic
      acid, ursolic acid, daucosterol and beta-sitosterol. CONCLUSION: These compounds
      were isolated from the plant for the first time.

PMID- 12525053
TI  - [Protective mechanism of tianmacuzhi granules in brain].
AB  - OBJECTIVE: To provide pharmacological evidence for the protective effects of
      Tianmacuzhi Granules (TMC) in mouse brain in a ischemia--reperfusion model.
      METHOD: Receptor binding test of NMDA receptor and M receptor in brain, GPx
      activity determination in brain and liver effected by different dose of TMC were
      performed. RESULT: TMC could reduce the NMDA receptor activity, increase the M
      receptor activity and GPx activity of cerebral cortex and hippocampus tissues
      significantly. CONCLUSION: TMC might antagonize ischemia-reperfusion injury of
      brain by reducing the glutamate neurotoxicity and increasing the function of
      cholinergic nerve and effects of anti-peroxidization in brain.

PMID- 12525054
TI  - [Studies on metabolism of oxymatrine by human intestinal bacteria].
AB  - OBJECTIVE: To study the oxymatrine metabolism induced by human intestinal
      bacteria and its absorbed metabolites in blood. METHOD: TLC and HPLC were used to
      examine oxymatrine and its metabolites, and UV, IR, NMR and MS were used to
      confirm the chemical structures of the metabolites. RESULT: Oxymatrine was
      transformed into matrine by human intestinal bacteria metabolism in vitro. Rats
      were given orally oxymatrine 100 mg.kg-1 and were decapitated 3 hours after
      administration, and their blood was taken to examine serum metabolites by TLC and
      HPLC, which revealed that oxymatrine and matrine were absorbed into blood.
      CONCLUSION: Oxymatrine will be transformed into matrine when it is given orally
      and both of the alkaloids can be absorbed to blood.

PMID- 12525055
TI  - [A study on AFLP fingerprinting of land races of Panax ginseng L].
AB  - OBJECTIVE: To obtain more information on DNA fingerprintings of five land races
      of Chinese ginseng, namely, Damaya (DMY), Changbo (CB), Yuanbangyuanlu (YBYL) and
      Huangguo (HG). METHODS: The five land races were detected by amplified
      restriction fragment polymorphism (AFLP) markers with 11 combined primers (M2,
      M3, M16, M20, M53, M56, M57, M68, M69, M72, M84 in Mse I). RESULT AND CONCLUSION:
      Only 4.6% polymorphic sites was found. It was further verified that only a little
      diversity existed among the land races. The polymorphic sites of CB were much
      more than those of the others, which suggests that there are more heterozygotes
      in CB populations, and it is closer to wild ginseng than the others.

PMID- 12525056
TI  - [Wind-damage effects on quality of heartwood of Lignum Santali Albi].
AB  - OBJECTIVE: To evaluate the wind-damage effects on quality of heartwood of Lignum
      Santali Albi. METHOD: GC-MS, TLC and pharmacodynamic test. RESULTS: The content
      of volatile oil from heartwood of Wind-damaged Lignum Santali Albi is 1.42%; the
      content of various components in the oil and the chromatography of different
      extracts are similar to those of reference drug and 25 years old trees.
      CONCLUSION: Wind-damage should accelerate the formation of heartwood of Lignum
      Santali Albi without influence on its quality.

PMID- 12525057
TI  - [Isolation and identification of a noval polyphenolic compound from Phyllanthus
      urinaria L].
AB  - OBJECTIVE: To investigate the chemical constituents of Phyllanthus urinaria.
      METHOD: Various chromatographic techniques were employed for isolation and
      purification. The structures were elucidated by spectral analyses. RESULT AND
      CONCLUSION: A novel polyphenolic compound was isolated and named phyllanthusin F.

PMID- 12525058
TI  - [Determination of cineole in banxiaxiexintang decoction different combinations of
      by GC].
AB  - OBJECTIVE: To the amount of 1,8-cineole in Banxiaxiexintang Decoction different
      combinations were determined by GC. METHOD: An OV-101 column (30 m x 0.32 mm) was
      used at 90 degrees C. RESULT AND CONCLUSION: The amount of cineole was 2-3 times
      in each combination than that in the separate Rhizoma Zingiberis.

PMID- 12525059
TI  - [Studies on chemical constituents of Cistanche tubulosa (Schenk) R. Wight].
AB  - OBJECTIVE: To investigate the chemical constituents of Cistanche tubulosa.
      METHOD: The chemical constituents were isolated by solvent extraction together
      with various chromatographic techniques including preparative HPLC. The
      structures were elucidated on the basis of chemical evidence and spectral data.
      RESULTS: Four iridoid glycosides, one lignan glycoside and one monoterpenoid were
      isolated from the 95% ethanol extract from the stem of C. tubulosa and identified
      as adoxosidic acid(I), 8-epiloganic acid(II), geniposidic acid (III),
      mussaenosidic acid(IV), (+)-syringaresinol-O-beta-D-gluco pyranoside(V) and 8
      hydroxygeraniol(VI). CONCLUSION: Compounds I and VI were isolated from the genus
      of Cistanche for the first time. Compounds III, IV and V were isolated from this
      plant for the first time.

PMID- 12525060
TI  - [Determination of nodakenin in Peucedanum].
AB  - OBJECTIVE: To establish a HPLC method to determine the contents of nodakenin in
      Peucedanum. METHOD: The determination method was achieved by RP-HPLC on an ODS
      column by UV detection at 334 nm; with nodakenin as external standard and H2O
      CH3OH-CH3CN(75:5:20) as mobile phase. RESULT: Several samples of 6 species of
      Peucedanum were analyzed by this method. The contents of nodakenin ranged from
      0.005%-3.090%. CONCLUSION: Nodakenin cannot be used to control the quality of
      Peucedanum for pharmaceutical use, but this method is a simple and feasible way
      to control the quality of P. decursivum.

PMID- 12525061
TI  - [Effects of musk glucoprotein on PAF production and cytosolic Ca2+ level in rat
      polymorphonuclear leukocytes in vitro].
AB  - OBJECTIVE: To investigate the effects of Musk glucoprotein on platelet activating
      factor (PAF) production and the concentration of cytosolic free Ca2+ in
      polymorphonuclear leukocytes of rat. METHODS: An in vitro incubation system was
      used, production of PAF and activity of acetyl transferase were measured by
      isotope incorporation, the concentration of cytosolic free Ca2+ was quantitated
      using the fluorescent Ca2+ indicator Fura-2. RESULTS: Musk-1 at concentration of
      1-100 micrograms.ml-1 can significantly inhibit production of PAF, activity of
      acetyl transferase and the increase of cytosolic Ca2+ concentration in
      polymorphonuclear leukocytes of rat. CONCLUSION: Part of mechanisms underlying
      antiinflammatory action of Musk-1 is through inhibiting the synthesis of PAF and
      the increase of cytosolic Ca2+ level.

PMID- 12525062
TI  - [Effect of anticancer polypeptide from Buthus Martensii venom on immune function
      in the H22-bearing mice].
AB  - OBJECTIVE: To observe the effect of anticancer polypeptide from Buthus Martensii
      Venom (APBMV) on Immune function in the H22-bearing mice. METHODS: The MTT
      colorimetric method, homolysin assay, lymphocyte transformation test, delayed
      hypersensitivity assay and WBC-count of peripheral blood were used in this study.
      RESULTS: APBMV could obviously augment NK activity, promote proliferation of
      lymphocytes induced by Con A, potentiate the response of DTH induced by DNCB,
      antagonize the decrease of WBC in peripheral blood induced by 5-Fu in the H22
      bearing mice. CONCLUSION: APBMV can obviously increase immune function in the H22
      bearing mice and antagonize hypoimmunity immunodeficiency or immunodeficiency
      induced by chemotherapy or the tumor.

PMID- 12525063
TI  - [Investigation on antibacterial activity of Forsythia suspense Vahl in vitro with
      Mueller-Hinton agar].
AB  - OBJECTIVE: To evaluate the antibacterial activity of Forsythia suspensa in vitro
      with different media. METHOD: MIC determination of Forsythia suspensa against
      Staphylococci was performed by the agar dilution method. RESULT: MIC90 of
      decoction of Forsythia suspensa against Staphylococcus epidermidis in M-H agar
      was 1:640, but in nutrient agar 1:40, the antibacterial activity with M-H agar
      being 16 fold higher than nutrient agar. CONCLUSION: The M-H agar should be
      recommended to replace nutrient agar as medium in the antibacterial experiment of
      Traditional Chinese medicine, and it is better to use multipoint inoculating
      device in the sensitivity test.

PMID- 12525064
TI  - [Traditional Chinese herbal drugs in military medicine: uses and prospects].

PMID- 12525065
TI  - [A review of the study on the processing of Chinese herbal drugs in past two
      years].

PMID- 12525066
TI  - [Recent advances in the research on pharmacokinetics of Chinese drug compounds in
      China].

PMID- 12525067
TI  - [Progress in the pharmacological study of Chinese herbal drug: polygonum
      cuspidatum].

PMID- 12525068
TI  - [Establishment of a TLC identification method for xuanshen(radix scrophulariae)].
AB  - OBJECTIVE: To establish a TLC identification method for Xuanshen(Radix
      Scrophulariae). METHOD: Using TLC with harpagoside and harpagide as reference
      substances. RESULT: A TLC identification method of Xuanshen has been established.
      The specificity of the method has been proved by a comparative detection of
      Xuanshen from different habitats and several crude drugs which are easily
      confused with Xuanshen. CONCLUSION: The method is simple, accurate and reliable.

PMID- 12525069
TI  - [Genetic transformation of autotetraploid Isatis indigotica fort. induced by Ri T
      DNA and plant regeneration].
AB  - OBJECTIVE: To establish an effective system for genetic transformation of
      autotetraploid Isatis indigotica by Agrobacterium rhizogenes. METHOD:
      Agrobacterium rhizogenes strains R1601, ATCC15834 and A4 were employed to induce
      hairy roots from autotetraploid Isatis indigotica, and the obtained hairy roots
      were developed into regenerated plants on solid MS media with different Kinds of
      plant growth regulators. RESULT: Root induction differed obviously. By three
      Agrobacterium strains. Hairy roots grew rapidly on solid MS medium without plant
      growth regulators and showed the typical hairy root phenotype: profuse branching,
      high density of root hairs and plagiotropism. And the transformation of Ri T-DNA
      was confirmed by opine analysis. The biomass of hairy roots increased nearly 35
      times regulator-free MS after suspended in plant growth two weeks. On solid MS
      medium with BA, adventitious buds were differentiated directly from hairy roots
      without callus formation. All of the adventitious buds were rooted on root
      induction medium and developed into regenerated plants. Opine analysis indicated
      the integration of Ri T-DNA in the transformed plants. CONCLUSION: Agrobacterium
      rhizogene can induce hairy roots from autotetraploid Isatis indigotica, and the
      obtained hairy roots can develop into regenerated plants.

PMID- 12525071
TI  - [Studies on chemical constituents of aerial parts of Verbena officinalis L].
AB  - OBJECTIVE: To search for new effective ant-early-pregnancy components from the
      aerial part of Verbena officinalis. METHOD: Compounds were isolated from the
      methanol extract of the herb by chromatography on silica gel column, and the
      structures were determined by physical and chemical evidences and spectroscopic
      analysis. RESULT: Two compounds were obtained and identified as 3,4
      dihydroverbenalin and daucosterol. CONCLUSION: The two compounds were obtained
      from this the herb for the first time and 3,4-didydroverbenalin is a new product.

PMID- 12525070
TI  - [Studies on the metabolism of gentiopicroside by rat intestinal flora].
AB  - OBJECTIVE: To study the metabolism of gentiopicroside by rat intestinal flora in
      vitro and time profiles of gentiopicroside and its metabolites in rat serum after
      oral administration of gentiopicroside. METHOD: Using high performance liquid
      chromatography (HPLC) for determination of gentiopicroside, gentianine and
      gentianal content of rat intestinal flora culture medium in vitro and rat serum
      sample in vivo. RESULT: Gentiopicroside was metabolized quickly in vitro by rat
      intestinal flora, consequently gentianine and gentianal content appeared.
      Gentianine and gentianal were observed after gentiopicroside oral administration
      4 times in rat serum sample, and gentiopicroside content decreased after oral
      administration 6 times. CONCLUSION: Gentianine and gentianal were the important
      bioactive metabolites of gentiopicroside in rats.

PMID- 12525072
TI  - [Studies on chemical constituents in the roots of Rabdosia japonica (Burm.f).
      Hara var. glaucocalyx (Maxin) Hara].
AB  - OBJECTIVE: To isolate and elucidate the chemical constituents in the roots of
      Rabdosia japonica. METHOD: The constituents were extracted by ether and isolated
      by chromatography on silica gel and ODS. The structures were determined by IR, H
      NMR, 13C NMR and MS spectra respectively. RESULT: Four compounds were elucidated
      as glaucocalgxin A, oleanolic acid, ursolic acid and daucosterol. CONCLUSION:
      Oleanolic acid and daucosterol were isolated from this plant for the first time.

PMID- 12525073
TI  - [Methodological studies on quantitative determination of beta-eudesmol in
      Atractylodes lancea (thunb.) DC].
AB  - OBJECTIVE: To establish methodologically a method for quantitative determination
      of beta-eudesmol in Atractylodes lancea. METHOD: GC, column: 3 mm x 2 m;
      stationary phase; 15% QF-1; support: Chromosorb WAW(60-80 mesh); detector:
      hydrogen flame ionization detector; injection chamber temperature: 210 degrees C;
      column temperature: 174 degrees C; carrier gas: N2:50 ml.min-1, air: 49 kPa,
      H2:58.8 kPa; sensibility range: 10(2) x 64; chart speed: 2.5 mm.min-1. RESULT:
      Average recovery ratio is 100.7% (n = 5). CONCLUSION: This method can be used to
      control the quality of A. lancea.

PMID- 12525074
TI  - [Effect of combined treatment of Shuanghuanglian and recombinant interferon alpha
      2a on coxsackievirus B3 replication in vitro].
AB  - OBJECTIVE: To investigate the effect of combined treatment of Shanghanglian
      (SHHL) and recombinant interferon alpha 2a on Coxsackie virus B3 replication.
      METHODS: Microdose cytopathogenic inhibition effect assay was used in Wish and
      Vero cultured cells. rIFN-alpha 2a was applied 12 hours before Coxsackievirus B3
      inoculation and SHHL was applied 1 hour after Coxsackievirus B3 inoculation.
      RESULTS: 0.125 mg.ml-1 SHHL has a synergism with rIFN-alpha 2a to inhibit CPE
      caused by Coxsackievirus B3 on the Wish and Vero cells. The anti-cox-sackievirus
      activity of combined treatment was 2.58 times higher than that of rIFN-alpha 2a
      treatment. CONCLUSION: This combined treatment of drugs may be useful in
      preventing and treating Coxsackie B3 Virus infection.

PMID- 12525075
TI  - [Experimental research on inhibitory effect of alcohol extracts from Loranthus
      yadoriki Sieb. on coxsackie B3 virus].
AB  - OBJECTIVE: To investigate the antiviral effect of two components (B and C) in the
      alcohol extracts from Loranthus yadoriki Sieb for development of new antiviral
      drugs for coxsackie B3 virus(CVB3). METHOD: Using ribavirin as positive control,
      the plaque reduction assay was adopted for pharmadynamic detection. RESULTS: In
      the HEp-2 cell system, with respect to direct virucidal activity and the
      inhibition on CVB3 infection and multiplication, ED50s of component B were 2.32
      micrograms.ml-1, 0.24 microgram.ml-1 and 1.91 micrograms.ml-1, respectively and
      those of component C, 1.44 micrograms.ml-1, 2.06 micrograms.ml-1 and 3.70
      micrograms.ml-1 respectively. For the inhibition on multiplication of CVB3, ED50
      of ribavirin was 7.55 micrograms.ml-1. CONCLUSION: Treatment indexes (TI) of the
      direct virucidal activity and inhibitory effects of component B on CVB3 infection
      and multiplication 22.6, 219 and 27.5 respectively; component C, 115, 165 and
      21.6; inhibition of ribavirin on CVB3 is 38, which is comparable to those of
      components B and C. It is thus suggested that the anti-CVB3 action of components
      B and C in the alcohol extracts from Loranthus yadoriki Sieb deserves to be
      exploited.

PMID- 12525076
TI  - [Effects of chuanxiong-chishao dispensing ratio on the pharmacokinetics of
      paeoniflorin in the canine].
AB  - OBJECTIVE: To explore the effects of dispensing ratio of Chinese herbs on the
      pharmacokinetic characteristics of effective components. METHODS: Paeoniflorin
      (PF) in serum was determined by RP-HPLC with UV-detector. The concentration-time
      data were fitted using 3P87 Pharmacokinetic Program, and the pharmacokinetic
      parameters were compared by t-test. RESULTS: The concentration-time curves of PF
      in both groups of Chuanxiong: Chishao 1:2 and 2:1 Xiongshao Pharmaceutics
      administrated intragastrically fitted open one compartment model. Parameters of
      Chuanxiong: Chishao 1:2 and 2:1 groups: Ka = 0.0082 +/- 0.0010 and 0.0088 +/-
      0.0011(min-1), Ke = 0.0060 +/- 0.0015 and 0.0071 +/- 0.0008(min-1), t1/2Ka =
      86.10 +/- 12.38 and 79.11 +/- 18.69(min), t1/2Ke = 119.95 +/- 27.23 and 98.14 +/-
      10.82(min), tpeak = 169.16 +/- 21.18 and 149.39 +/- 29.51(min), Cmax = 3845.89 +/
      716.70 and 1635.81 +/- 230.95 (micrograms.L-1) respectively. The pharmacokinetic
      parameters of the two groups had no statistically significant differences (p >
      0.05). CONCLUSION: Different formulae of Chinese herbs do not always result in
      changes of pharmacokinetic characteristics of some one component.

PMID- 12525077
TI  - [Malignant transformation of human bronchial epithelial cells induced by
      benzo(a)pyrene metabolite dihydroxyepoxy benzo pyrene].
AB  - The malignant transformation of human bronchial epithelial cell 16HBE induced by
      benzo (a) pyrene metabolite--dihydroxyepoxy benzo pyrene (BPDE) was studied.
      16HBE cells were treated several times with BPDE at different concentrations in
      vitro. The identification on the malignancy of transformed 16HBE cells was
      investigated. The transformed cells in foci were proliferated rapidly, exhibited
      in extensive random orientation and crossed over. The transformed cells could
      grow on soft agar. The colony forming frequency of each BPDE group on soft agar
      was significantly higher than that of control group and showed dose-reaction
      relations with the concentrations of BPDE. The transformed cells could grow into
      tumors in nude mice. The tumor was squamose carcinoma confirmed by
      histopathological examination. The culture system in this study provided a
      potential tool for studying the molecular mechanism of carcinogenesis of human
      bronchial epithelial cells induced by BPDE.

PMID- 12525078
TI  - [Effects of aluminum intake on the content of aluminum, iron, zinc and lipid
      peroxidation in the hippocampus of rats].
AB  - Effect of long-term exposure to aluminum on the content of aluminum, iron, zinc,
      copper and the lipid peroxidation in hippocampus was studied. Sprague-Dawley rats
      were randomly divided into four groups by body weight. Aluminum chloride was
      added to diet at doses of Al3+ 0, 11.2, 55.9 and 111.9 mg/kg BW for successive 90
      days. Neuro-behavioral tests consisted of open field and passive-avoidance
      conditioning were performed. SOD and GSH-Px activities and MDA levels were
      detected by spectrophotometry. The values of aluminum, iron, zinc and copper were
      measured by atomic absorption spectroscopy. The spontaneous motor ability in the
      open field and the latency of passive avoidance were decreased as compared with
      the controls. The concentration of aluminum was increased and iron and zinc were
      decreased copper was not changed significantly; the activities of SOD and GSH-Px
      were reduced, while the value of MDA was increased in hippocampus. The results
      suggested that long-term aluminum-exposure could lead to high accumulation of
      aluminum in hippocampus, which could disturb the normal distribution of iron and
      zinc, decrease the activities of antioxidase and increase the level of lipid
      peroxidation. Accumulation of aluminum and accompany with reduction of iron, zinc
      in hippocampus and oxidative damage to hippocampus might interpret the
      neurotoxicity of aluminum.

PMID- 12525079
TI  - [Serum glutathione S-transferase in bromobenzene-induced acute hepato-toxicity in
      mice].
AB  - The activity of serum glutathione S-transferase (GST) was tested in bromobenzene
      induced acute hepatotoxicity in mice. The data showed that a lot of small local
      necrosis in liver biopsy was observed and serum GST activity was increased after
      2 h of treatment with bromobenzene (150 mg/kg i.p.) in mice. Serum alanine
      transaminase (ALT) activity was also gradually enhanced after 8 hours of
      treatment. The most obvious changes were at 16 hours of bromobenzene treatment,
      and serum GST activity was firstly restored to normal level after 24 hours of
      treatment. There were good positive correlations between serum GST, ALT, as well
      as serum GST and the changes on liver biopsy. Evaluating analysis of the
      diagnosis test showed that the sensitivity, specificity and accuracy was 89%, 75%
      and 82% in serum GST test, and 39%, 92% and 64% in serum ALT test respectively.
      The ROC work curve also demonstrated that serum GST was more sensitive and
      specific than serum ALT.

PMID- 12525080
TI  - [Effect of manganese on the ratio of micronucleus cells in mice marrow].
AB  - The ratio of micronucleus in the bone marrow cell of mice induced by manganese
      (Mn2+, MnCl2) through intraperitoneal injection at doses of 0, 25, 50 and 100
      mg/kg respectively was investigated. The number of micronucleus cells per 1000
      polychromatic erythrocyte (PCE) from breast bone marrow was counted. The results
      showed that micronucleus ratio in bone marrow cells were 12.0 and 16.4 per 1000
      in the medium and high dosage groups, which were higher than that of control (P <
      0.01). There is no distinct difference between the low dosage group and the
      control group (P > 0.05), but show a rising trend with the dosage of Mn2+. It
      indicated that the higher the dose of MnCl2, the stronger the toxic effect to the
      micronucleus in bone marrow cells. MnCl2 is considered having mutation to
      chromosome and potential heredity toxicity.

PMID- 12525081
TI  - [Developmental toxicity of Al(NO3)3 on rat embryos].
AB  - The developmental toxicity and its mechanism of Al(NO3)3 on embryos in SD rats
      were studied. On the 9.5th day of gestation, the embryos were incubated in a
      whole-embryo culture system with Al(NO3)3 at concentrations of Al3+ from 0.6 to
      9.0 micrograms/ml in culture media for 48 hrs. Viable embryos were evaluated by
      Brown's morphological scoring system, and the diameter of yolk sac, crown-rump,
      head length and the dry weight of embryos were measured. There was a dose
      dependent relations of decreasing embryo development with increasing
      concentrations of Al3+. Yolk sac diameter, head length, dry weight and heart,
      forelimb as well as neural tube scores decreased significantly at 1.2
      micrograms/ml (P < 0.05). When embryos were exposed to Al3+ at > or = 3.0
      micrograms/ml, the embryonic development and morphological differentiation were
      obviously inhibited(P < 0.05); meanwhile, the incidence of dysmorphogenesis
      significantly increased, including neural tube defects and dorsiflexion
      teratogenesis. The results suggested that aluminum might be a developmental
      toxicant and dysmorphogenesis agent.

PMID- 12525082
TI  - [Effects of manganese, zircon and lithium alone on rat liver lipid peroxidation].
AB  - Lipid peroxide (LPO) in rat liver was detected by malondiadehyde (MDA)
      colorimetry. The effect of manganese, zircon and lithium alone on lipid
      peroxidation in rat liver was also studied. The results showed that manganese and
      zircon at the doses of (9.862-1.972) x 10(-4) and (0.1972-9.862) x 10(-5) nmol/L
      respectively decreased LPO in rat liver(P < 0.01). Lithium inhibited lipid
      peroxidation at the dose of (19.72-1.972) x 10(-4) nmol/L, and induced lipid
      peroxidation at higher concentration.

PMID- 12525083
TI  - [Effects of selenium on the damage of learning-memory ability of mice induced by
      fluoride].
AB  - Sodium fluoride added with or without sodium selenite in deionized water was
      administered to male mice for 8 weeks. The influences of fluoride on learning
      memory behavior were tested on Y-maze, and the ultrastructure of Gray I synaptic
      interface in the CA3 area hippocampus was quantitatively analyzed by electron
      microscopy and computer image processing appliance. The main results showed that
      the learning capability of mice drinking higher concentration of fluoride
      presented remarkable deterioration. The thickness of post-synaptic density (PSD)
      was decreased. The width of the synaptic cleft was remarkably increased. It was
      found that combined administration of fluoride and proper concentration of
      selenium could decrease the toxic effect of fluoride. There were synergetic
      toxicities if the concentration of selenium was too high. The results suggested
      that selenium might antagonize the neurotoxicity of fluoride on behavior and
      morphology.

PMID- 12525084
TI  - [Detection of DNA crosslinks with comet assay].
AB  - A simple and rapid method for the detection of DNA cross-links was explored. DNA
      cross-links was induced by formaldehyde (FA) in TK6 cells. Hydrogen peroxide was
      used as a standard DNA breakage agent. Two protocols on detecting DNA cross-links
      with comet assay were tested and compared. The results showed that with
      increasing FA, the length of DNA migration caused by H2O2 was decreased. When the
      level of FA was 1000 mumol/L, no any tailed cell could be observed, the migration
      of DNA was inhibited completely even H2O2 was used. The detection of DNA cross
      link could be tested by both protocols. However, when the DNA cross-link agent
      (FA) was added to the cells before the treatment with DNA breakage agent (H2O2),
      the result of the scheme was much better than that in the opposite order. The
      former scheme was much easy to be manipulated, with no influence from DNA repair
      and had better dose-response relationship in the detection of DNA cross-links.
      The comet assay is indeed a sensitive, convenient and rapid method for the
      detection of DNA cross-link.

PMID- 12525085
TI  - [Distinguishing apoptotic cells from DNA strand-broken cells by comet assay].
AB  - Apoptosis of immature thymocyte of mice induced by dexamethasone and DNA strand
      broken cells induced by K2Cr2O7 were tested by comet assay. The results showed
      that the morphology of apoptotic cells assayed by comet was special. Under the
      same condition, the time of apoptotic cells running on electrophoresis was
      shorter than DNA-broken cells. The length of comet tail of DNA strand-broken
      cells increased in a dose-response relation with the increase of K2Cr2O7,
      whereas, the apoptotic index increased with the dosage of dexamethasone. While
      DNA damage was repairing, apoptosis continued to process. The DNA strand-broken
      cells could be obviously seen while DNA damage was repairing. It was suggested
      that comet assay could be used to detect DNA strand break sensitively, but also
      could distinguish different grades of DNA damage, which is helpful for studies on
      the etiology, progressing and outcome of cancer.

PMID- 12525086
TI  - [Factors affecting arsenic removal with copolymer coagulant and their mechanism].
AB  - The removal of arsenic from drinking water with copolymer coagulant was
      investigated. The effect of the component, additive substance of the coagulant
      and filtration were tested by employing a orthogonal analysis. The results showed
      that the arsenic removal with ferric sulfate was better than that with ferric
      aluminum copolymer and polysilicon metal salt. Adding active carbon powder or
      kaoline could not enhance the efficacy of arsenic removal. However, the removal
      rate was improved by filtration after using coagulates, and sand filtration was
      feasible. The efficacy of arsenic removal could be affected by the column height
      filled with sand and the diameter of sand. After arsenic adsorption model fitted,
      the Lang-muire isotherm was matched. The main mechanism of arsenic removal by
      coagulation should be adsorption.

PMID- 12525088
TI  - [Effect of exercise on leptin in streptozotocin-induced diabetic rats].
AB  - The effect of exercise on leptin in streptozotocin(STZ)-induced diabetic rats was
      investigated. Four group of SD rats (10 in each group) including exercise STZ
      diabetic group, non-exercise STZ diabetic group, exercise normal group and non
      exercise normal group were used in the study. Exercise groups were treated with
      treadmill. The results showed that: (1) blood glucose of STZ diabetic rats was
      higher, serum insulin, C-peptide and leptin level were lower than that of normal
      rats; (2) blood glucose was decreased, and blood insulin and C-peptide were
      increased in exercised STZ diabetic group. The levels of leptin in plasma, brain
      and adipose tissue were increased in exercise groups. It is concluded that
      appropriate exercise training may have impacts on insulin and leptin production
      to correct the abnormal glucose metabolism and energy metabolism in diabetic
      rats.

PMID- 12525087
TI  - [Study on an enhancing agent for removing arsenic from drinking water].
AB  - Drinking water contaminated by arsenic for an extended period of time could be
      detrimental to the health of people. Some preliminary symptoms could be
      alleviated by drinking water non-contaminated. It is important to develop an
      arsenic removal agent with a specific property of most efficient, cost-effective
      and easy for operation. The results showed that the capacity of the agent
      developed in this study was 10 times higher for arsenic removal than other agent
      available. The lowest arsenic content of the treated water was 0.05 mg/L. The
      special function of this agent was arsenic removing without changing other
      components and the concentrations of other elements in the treated water. The
      operation and management was simple without adjusting pH of the influent and
      effluent water. The agent was 5 times cheaper in cost than alumina or activated
      carbon, because it was a reusable oxidation-catalyst. Therefore, the agent could
      be widely applied in drinking water plants or used as a purifier at home in the
      high arsenic areas.

PMID- 12525089
TI  - [Effects of beta-carotene and vitamin C on the expression of c-myc in human
      leukemic cell].
AB  - In order to study the effects of beta-carotene and vitamin C(VC) on the
      expression of c-myc oncogene in human leukemic cell, myelogenous leukemic cell
      line HL-60 was cultured in vitro with standard methods. Trypan blue exclusion
      test and Northern blotting hybridization were used to detect the cell
      proliferation and the expression of c-myc gene. The results showed that the
      proliferation of HL-60 cell was inhibited after exposed to VC(5, 10, 100 mumol/L)
      and the occurrence of proliferation was earlier at lower concentration of VC(5
      mumol/L). beta-carotene at 10-100 mumol/L could inhibit the proliferation of HL
      60 cell in a dose dependent manner. VC(5 mumol/L) had no influence on the
      expression of c-myc gene(P > 0.05), but beta-carotene could up-regulate the
      expression of c-myc(P < 0.05). Our observations suggested that the inhibitory
      effect of beta-carotene on the proliferation of leukemic cells was caused by
      inducing apoptosis of HL-60 through up-regulating the expression of c-myc gene;
      however, the inhibitory effect of vitamin C on cell proliferation was not related
      to the expression of c-myc gene.

PMID- 12525090
TI  - [Effect of iron deficiency anemia on the reproduction of female rats and the
      development of their offspring].
AB  - The effects of iron deficiency anemia(IDA) on the reproduction of female rats and
      the development of their offspring were studied. Four-week-old female Wistar rats
      were randomly divided into two groups. The rats in experimental group and control
      group were fed on low iron or normal diet respectively for 14 weeks, and then
      they were mated with normal adult male rats. The development and growth of the
      newborn, weanling and four-day-old offspring was observed and the trace element
      Fe, Zn, Cu, Mn and Se in serum were measured. IDA made notable impacts on the
      reproduction of female rats with small sized litters, less living fetal rats. The
      survival rate of female rats in the IDA group was less than that in control
      group. Hemoglobin and packed cell volume in blood were lower in IDA group than
      those in control group(P < 0.0001). The content of serum Fe and Cu in IDA group
      was also lower than that in control group. Iron deficiency might cause metabolism
      disorders of other trace element.

PMID- 12525091
TI  - [Effects of exogenous adenosine 5'-monophosphate on proliferation and apoptosis
      of small intestinal epithelial cells].
AB  - The effect of exogenous adenosine 5'-monophosphate (AMP) on proliferation and
      apoptosis of a normal rat small intestinal epithelial cell line, IEC-6, was
      investigated. Proliferation of IEC-6 was measured by MTT. Cell cycle and
      apoptosis was determined by flow cytometry. Expression of Bax was detected by
      immunohistochemistry. The results showed that AMP remarkably inhibited the
      proliferation of IEC-6 in a dose- and time-dependent way. AMP also significantly
      changed the distribution of cell cycle, arrested cells in S phase and enhanced
      apoptosis by inducing Bax expression.

PMID- 12525092
TI  - [Studies on the inhibitory effects of tea polyphenols and tea pigments on liver
      precancerous lesion in rats].
AB  - The chemopreventive effects of tea polyphenols and tea pigments on liver
      precancerous lesion in rats were investigated. The results showed that the
      density and area of GST-P in the tea-treated groups were significantly reduced as
      compared with the positive control group. Furthermore, tea polyphenols and tea
      pigments induced the expression of p21WAF1 protein, inhibited the expression of
      Bcl-2 protein and induced the expression of Bax protein. It is concluded that GST
      P was significantly inhibited by tea polyphenols and tea pigments and inhibition
      of cell proliferation and induction of apoptosis may be the two important
      mechanisms.

PMID- 12525093
TI  - [Comparison of production and characters of antisera from rabbits and laying
      hens].
AB  - Rabbits and laying hens were immunized with the conjugate of aflatoxin B1 oxime
      and bovine serum albumin (AFB1 O-BSA). The production processes, titers and
      specificities of antisera from rabbits and laying hens were investigated. In
      rabbits, the antisera started to be obviously produced after 60 days when the
      conjugate was firstly injected, reached peaks after 120 days, and began to go
      down after 135 days; while in laying hens, the antisera started to be largely
      produced after 90 days of the first injection, arrived to peaks after 135 days,
      and began to go down after 165 days. The maximum enzyme linked immunosorbent
      assay(ELISA) titer of rabbits' antisera was up to 1:30,000, whereas the maximum
      ELISA titer was only 1:8000 in laying hens. There are no apparent difference in
      the sensitivities and specificities of rabbits' and laying hens' antisera. Both
      antisera from rabbits and from laying hens can be used as ELISA reagents
      detecting AFB1 in agricultural commodities.

PMID- 12525094
TI  - [Effect of monascus on improving the hemorheology of rats with high blood
      lipids].
AB  - The effects of monascus on the hemorheology of rats with high blood lipids were
      observed. Wistar rats were fed with high cholesterol to establish a model of
      hypercholesterolemia. Monascus at the dosage of 0.0, 0.6, 1.2 g/(d.kg BW) was
      administrated for 28 days. Normal control group was fed with standard rat chow.
      Rats in 0.0 g/kg BW group became hypercholesterolemia clearly. Monascus decreased
      TC, TG, and increased HDL-C significantly in the experimental groups. Monascus
      can significantly increase the deformability of erythrocyte(IDEI) and decrease
      aggregation index(AI), platelet adhesion rate(PADT) and blood viscosity at the
      shear rate of 5 s-1. No significant difference of platelet aggregation (PAGT) in
      groups was observed.

PMID- 12525095
TI  - [A survey on the effects of "Dietary Guideline" nutrition education project].
AB  - A survey on the nutrition knowledge, attitude and behavior of 5145 persons from
      five cities of four provinces, Shandong, Guangdong, Sichuan and Heilongjiang,
      before and after the nutritional education project on "Dietary Guideline" has
      been effectively conducted. An obviously good effect has been achieved among the
      residents, middle and primary school students and elderly people. Before the
      nutritional educational project has been carried out, the people who
      understanding the "Dietary Guideline" was only 12.0%, 29.2% and 15.2% of
      residents, the elderly and students respectively. But after education, the rates
      raised to 93.4%, 99.0% and 91.9% respectively. Nearly 90% of residents and the
      elderly got to know the "Dietary Guideline" through the materials distributed
      from the project. The nutrition knowledge score was improved greatly after the
      project was conducted. The attitude towards learning nutrition knowledge was
      good. At the same time, some dietary behavior and the life style of people had
      been modified. These results indicated that nutrition education is very important
      on improving people's nutrition knowledge level, changing people's unhealthy
      living attitudes and dietary habits.

PMID- 12525097
TI  - [Validation and comparison of ISO standard method for the examination of fluoride
      in drinking water].
AB  - The validation of ISO standard method for the examination of fluoride in drinking
      water was introduced. The test for compensating interference, standard curves,
      accuracy, precision and the minimum detection limit etc were included. The
      comparison between ISO method and others was made. The results indicated that the
      ISO method was better in anti-interference, wider linear range and higher
      precision. The points designed were reasonable. The method is superior to other
      methods in the same kind, and it should be adopted and extended.

PMID- 12525096
TI  - [Study on FM100-HUE color vision in male workers exposed to lower concentration
      of carbon disulfide].
AB  - The effect of CS2 on color vision in workers exposed to CS2 was explored. The
      color discrimination in 191 exposed and 93 non-exposed male workers was studied
      by a Farnsworth Munsell 100-HUE (FM100-HUE) test. The results showed that the
      time weighted average (TWA) concentration of CS2, determined by Japan GC-17A gas
      chromatography, was (14.75 +/- 6.89) mg/m3 in a long rayon workshop and (16.30 +/
      5.42) mg/m3 in a short rayon workshop. Higher FM100-HUE color vision score was
      often in the exposed group (106.9) than in the controls (78.3). The
      discrimination to green and blue zone was also significantly impaired (P < 0.05).
      It is concluded that the color vision was disturbed in workers exposed to CS2.
      The workers should be followed by health surveillance.

PMID- 12525098
TI  - [Detection of aflatoxin-albumin adducts in human serum and its application].
AB  - Exposure to aflatoxin B1 (AFB1) is one of the major risk factors in the etiology
      of human hepatocellular carcinoma (HCC). The development of highly sensitive and
      specific methods for detecting AFB1 and its macromolecular biomarkers are
      critical for identifying individuals at risk for hepatocellular carcinoma. The
      detection of aflatoxin-albumin adducts (AFB-ALB) in serum has been used to
      investigate the relationship between aflatoxin exposure and HCC. A more sensitive
      and reliable method to detect AFB-ALB in serum was modified by separating serum
      albumin with Microcon-50 microconcentrators in stead of using precipitation. The
      method could separate serum albumin quickly and make protein digested in the same
      container. Thus, the step for transferring samples was reduced and recovery rate
      was improved. The AFB-ALB adducts were then determined by radioimmunoassay. The
      AFB-ALB adducts of human serum samples from Qidong, Jiangsu Province, and Fusui,
      Guangxi Zhuang Autonomous Region of the People's Republic of China were detected.
      The results indicated that the exposure of AFB1 is common and the positive rate
      for AFB-ALB adducts in serum of these populations is high.

PMID- 12525099
TI  - [Culture and identify the endothelial cells of human umbilical vein].
AB  - In order to improve the routine culture method for vascular endothelial cells,
      endothelial cells of vein from newborn umbilical cord were successfully isolated
      with combined using 0.1% collagenase and 0.25% trypsin (1:1). The endothelial
      cells were further abrated by mechanical method. The composition of culture
      medium was simplified by not adding vascular endothelial cell growth factor and
      heparin. The cultured cells were verified as vascular endothelial cells by
      morphology, ultramicromorphology and immunohistochemistry.

PMID- 12525100
TI  - [Health effects of indigestible carbohydrates on colon].
AB  - Indigestible carbohydrates are closely related to the growth of microbes in colon
      and the health status of colon. People are now becoming more and more interested
      in indigestible carbohydrates and many studies have been carried out. In this
      review, the classification and the digestion of indigestible carbohydrates, and
      the health effects of their fermented products on colon were introduced.

PMID- 12525101
TI  - [Current status of Tibetan herbal drugs and their modernization].

PMID- 12525102
TI  - [Studies on resources of ethnomedicine Gaultheria leucocarpa var. yunnanensis].
AB  - OBJECTIVE: To study the resources of G. leucocarpa var. yunnanensis for further
      development of this drug. METHOD: Field investigating, consulting with relevant
      experts and looking into available specimens. RESULTS AND CONCLUSION: G.
      leucocarpa var. yunnanensis is widely distributed in the southern regions of the
      Yangtze River. The field investigation suggests that the distribution center is
      situated in Yunnan province, mainly in Kunming, Chuxiong and Dali counties. The
      climate in these areas is moderate and moist. G. leucocarpa var. yunnanensis is
      not a dominant species in this natural environment. In some places, it grows with
      other species of Gaultheria, such as G. fragrantissima, G. tetramera, G.
      griffithiana and G. leucocarpa var. cumingiana. It is distributed at altitudes
      from 400 m to 3,500 m. Accustomed to different sunshine conditions, G. leucocarpa
      var. yunnanensis prefers stronger sunlight and commonly grows on sunny slopes,
      seldom in dense forest, propagating itself by roots. As a folk medicine, G.
      leucocarpa var. yunnanensis is commonly used to treat rheumatic arthritis(RA),
      dazzling, suppressed menstruation, cold, cough, asthma, strain hematemesis,
      eczema, ascites, wound, amebic dysentery, acute and chronic prostatitis. It is
      suggested that further pharmacological and clinical researches of this plant be
      concentrated on the treatment of RA and relief of aches.

PMID- 12525103
TI  - [Nuclear ribosomal RNA small subunit (18S rRNA) nucleotide sequencing and
      characterization of sailonggu(whole bone of Myospalax baileyi Thomas)].
AB  - OBJECTIVE: Sequencing the nuclear ribosomal RNA small subunit (18S rRNA) gene of
      Myospalax baileyi (Cricetidae) to develop an ultimate and definitive means for
      origin identification of genuine Sailonggu. METHODS: The total DNA was prepared
      from dried tail tissues. The nuclear 18S rRNA gene region was amplified by PCR
      using a consensus primer set and its nucleotide sequence was determined by PCR
      direct sequencing. The characteristic analysis of 18S rRNA sequences was
      generated using software program Genetyx-SV/R Version 10.1. RESULTS: The entire
      18S rRNA gene region of M. baileyi spanded 1851 bp in length. Although multiple
      alignment of sequence indicates that there are only lower homology (72.04%
      72.18%) comparing with its two alias Mus musculus (GenBank Accession number
      X00686) and Rattus norvegicus (M11188) (Muridae), their highly conservative
      domain is located in 1020-1509 nt. There are many variable sites from upstream of
      5'-end, which could provide a novel information for molecular recognition of
      Sailonggu. CONCLUSION: DNA sequencing could be a useful and reliable tool in the
      origin identification of genuine Sailonggu.

PMID- 12525104
TI  - [Genetic transformation of Panax ginseng C.A. Meyer induced by root inducing
      plasmid(Ri) of Agrobacterium rhizogenes].
AB  - OBJECTIVE: To obtain the hairy root of Panax ginseng (HRPG). METHOD: HRPG was
      obtained by infecting the germ-free seedling, cotyledon, leaf the blade, Petiole
      with Agrobacterium rhizogenes 15,834 harbouring agropine-type Ri plasmid. The
      transformation was proved by PCR and TLC. RESULT: HRPG grew rapidly on hormone
      free medium and showed typical phenotype of hairy root. The induced rate and time
      can be improved by adding exogenous hormone and AS(hydroxyacetosyringone). PCR
      analysis confirmed the integration of TL-DNA, including 564 bp rolC sequence in
      the HRPG. Opine analysis evidenced the integration and expression of TL-DNA. The
      total saponin in HRPG (2.486%) was higher the than control(1.403% Panax ginseng).
      CONCLUSION: HRPG grows rapidly and proves high in content of ginseng saponin.
      This culture system of HRPG will be useful for the production of active
      components in ginseng.

PMID- 12525105
TI  - [Studies on preparation of herba epimedii total flavonoids phytosomes and their
      pharmaceutics].
AB  - OBJECTIVE: To optimize preparation techniques for Herba Epimedii flavonoid
      phytosomes (EFP) and explore their suitable pharmaceutics. METHODS: To optimize
      the preparation conditions by means of uniform design and step regression,
      prepare Herba Epimedii total flavonoid phytosomes by means of solvent evaporation
      and investigate the accumulative dissolution of different ratios of EFP-PVP
      precipitates by means of dissolution release. RESULT: The optimized preparation
      conditions are as follows: solvent-tetrahydrofuran, lecithin to PVP--2.5 times,
      temperature--40 degrees C and reaction--3 hours. Oil/water apparent partition
      coefficient of icariin was enhanced more than 4 times by phospholipid. The
      accumulative dissolution of Herba Epimedii flavonoids of EFP-PVP precipitate was
      significantly higher than that of its physical mixture and Herba Epimedii extract
      tablet. CONCLUSION: Phospholipid can effectively enhance the oil/water apparent
      partition coefficient of icariin, and PVP can improve the dissolution of Herba
      Epimedii phytocomes, but the pharmacokinetics needs further study.

PMID- 12525106
TI  - [Compounds from roots of Chirita fimbrisepala Hand.-Mazz].
AB  - OBJECTIVE: To study the chemical constituents the roots of Chirita fimbrisepala.
      METHOD: The constituents were extracted with solvent, separated and purified with
      chromatographic methods, identified by NMR, MS, UV, IR and physical-chemical
      constants. RESULT: Three flavonoids mahuangchiside(I), hispidulin (II) and
      kaempferol(III) were isolated with daucosteral(IV). CONCLUSION: I is a new
      compound elucidated as hispidulin-7-O-beta-D-xylopyranosyl-(1-->2)-beta-D
      xylopyranoside, named mahuangchiside, II and III were isolated for the first time
      from the family Gesneriaceae, and IV was isolated for the first time from the
      genus Chirita.

PMID- 12525107
TI  - [Studies on chemical constituents from root of Saposhnikovia divaricata (Turcz.)
      Schischk].
AB  - OBJECTIVE: To study the chemical constituents in the root of Saposhnikovia
      divaricata. METHOD: The compounds were isolated and identified by column
      chromatography and 1H, 13C NMR data. RESULT: Twenty-four compounds were isolated
      and identified. CONCLUSION: Seven compounds were isolated from this plant for the
      first time.

PMID- 12525108
TI  - [Studies on the semi-biosynthesis of L-ephedrine (I). Studies on the biosynthesis
      of L-phenyl acetyl carbinol].
AB  - OBJECTIVE: The optimal biosynthesis of L-PAC by immobilized Sc-5 yeast cell was
      systematically studied in this paper. METHOD: Biosynthesis. RESULT AND
      CONCLUSION: The average of L-PAC yield produced by the immobilized Sc-5 yeast
      cell is > or = 2 g.L-1 and half life > or = 240 h.

PMID- 12525109
TI  - [Studies on the fingerprint of radix notoginseng and its preparation].
AB  - OBJECTIVE: A fingerprint of raw material, extracted and injections of radix
      notoginseng has been studied and provides the quality information. METHOD:
      Polaris C18-A column was used, with mixtures of acetonitrile and water as mobile
      phase in a gradient mode. The wavelength of measurement was 203 nm. RESULT:
      According to the selected chromatographic conditions, a good fingerprint of radix
      notoginseng and its extract, preparation has been described. CONCLUSION: The
      method is simple, accurate with good reproducibility. It may be practical value
      for the quality control of sample for radix notoginseng and its preparation.

PMID- 12525110
TI  - [Effects of baicalin on hepatocyte apoptosis induced by TNF-alpha and act D in
      rats].
AB  - OBJECTIVE: To study the effects of baicalin on rat hepatocyte apoptosis induced
      by tumor necrosis factora (TNF-alpha) and actinomycin D (Act D) in vitro.
      METHODS: Hepatocytes were cultured with different concentrations of baicalin and
      the cell apoptosis was induced by TNF-alpha and Act D in vitro. After culturing
      for 24 h, the activity of hepatocysts was examined by MTT assay and the function
      of hepatocytes for secreting albumin was detected by bromocresolum Viride method.
      Agarose gelelectrophoresis and flow cytometric analysis were used to determine
      the apoptotic cells. RESULTS: The actively of the hepatocyte (A) and content of
      albumin (ALB) in the supernatant of cultured cells in the groups of 0.2
      microgram.ml-1 and 2.0 micrograms.ml-1 of baicaline were significantly higher
      than those in apoptotic model group (A: P < 0.01; ALB: P < 0.01); respectively
      Even the ALB value in the group of 0.2 microgram.ml-1 baicalin was higher that of
      black control group (P < 0.01); The clear "ladder-like" streak-band of DNA
      fragments was found only in the apoptosis model group by the agarose gel
      electrophoresis. The flow cytometry showed that all the apoptosis rates in the
      three baicalin groups were lower than that of the apoptotic model group (P <
      0.01). CONCLUSION: Baicaline can restrain rat hepatocyte apoptosis induced by TNF
      alpha and ActD in vitro.

PMID- 12525112
TI  - [Authentication of traditional Chinese herbal medicines (TCHM) by fingerprints of
      characteristic general constituents].
AB  - OBJECTIVE: To describe the theory, scientific significance, distinguishing
      features and authentication feasibility of TCHMs by spectral fingerprints of
      characteristic general constituents. METHOD: Previous relevant investigations and
      literatures were summed up in the field, and the present situation on the
      authentication of TCHMs at home and abroad was analysed. RESULT: The
      characteristic general constituents of TCHMs can be obtained by an appropriate
      procedure. Their compositions and structures can be determined by spectral
      fingerprints, especially the 1HNMR fingerprint. The species of TCHMs can be
      identified accurately by these fingerprints. Besides, the quality of TCHMs can be
      evaluated by the contents of their GCEs. CONCLUSION: Fingerprint authentication
      of characteristic general constituents of TCHMs has profound significance for the
      species identification and quality evaluation of TCHMs.

PMID- 12525111
TI  - [Effect of liuwei dihuang decoction, on the cytokine expression in splenocytes in
      AA rats].
AB  - OBJECTIVE: The effect of Liuwei Dihuang decoction (LW) on the function of splenic
      T helper cells (Th) was studied and compared with those of the immune inhibitors
      such as cyclophosphamide (Cy) and cyclosporin A (CsA) in AA rats. METHODS: The
      expression of mRNA for IFN-gamma, IL-2, IL-4 and IL-10 in splenic T-Lymphocytes
      of adjuvant arthritis (AA) rats was evaluated using reverse transcription
      polymerase chain reaction (RT-PCR) technique. RESULTS: mRNA expression level of
      IL-2 had a tendency to elevate, but the mRNA expression levels of IFN-gamma, IL-4
      and IL-10 were significantly decreased in AA rats in comparison with control
      groups. LW treatment significantly inhibited the mRNA expression of IL-2 and
      promoted the expression of IFN-gamma, IL-4 and IL-10 in splenocytes of AA rats,
      with an obvious characteristic as compared with that of Cy or CsA. CONCLUSION: LW
      can correct the indifferent balance of the functions of splenocyte Th1/Th2 in AA
      rats.

PMID- 12525113
TI  - [Identification of medicinal plant Xanthium L. produced in China].
AB  - OBJECTIVE: To gain a clear idea on the resources and pharmacognostic
      identification of medicinal plant Xanthium in China. METHOD: Identification of
      botanical origin, analysis of fruit shapes and properties, microscopic
      characteristics, TLC and UV. RESULT: Identification criteria have been worked out
      for Xanthium and its confused species. CONCLUSION: The resources of medicinal
      plant Xanthium may be appropriately expanded.

PMID- 12525114
TI  - [Plant regeneration from Agobacterium-mediated CTV-cp gene transformation of
      Poncirus trifoliata Raf].
AB  - OBJECTIVE: To lay a foundation for the resistant breeding, the anti-virus CTV-cp
      gene was transformed into the epicotyles mediated by Agrobacterium tumefaciens in
      Poncirus trifoliata. METHOD: The explants used for the genetic transformation
      were the epicotyls from P. trifoliata. The Agrobacterum tumefaciens strain was
      EHA101 containing vector plasmid pGA482GG. The coat protein gene (CTV-cp gene),
      GUS gene and NPT II gene were introduced into the transformation plasmid.
      RESULTS: Ceftaxime used as antibiotics was better than carbenicillin. The
      concentration was 300 mg.L-1; The selection pressure for kanamycin was 50 mg.L-1;
      70.0% of the resistant plants were GUS-positive; extra gene was proved to be in
      P. trifoliata plant by southern blot examination. CONCLUSION: An effective
      genetic transformation mediated by Agrobacterium tumefacines, which harbours a
      CTV-cp gene, has been developed in P. trifoliata. Transgenic CTV-cp plants were
      obtained.

PMID- 12525115
TI  - [Studies on saponin accumulative in regularities Panax notoginseng (Burk) F. H.
      Chen].
AB  - OBJECTIVE: To determine the optimal harvest time for P. notoginseng through
      studying the changes of saponin contents with growth periods. METHODS: P.
      notoginseng samples were collected from the experimental plot regularly, and then
      the contents of total saponin and some main single saponins were analyzed by
      HPLC. RESULTS: Total saponin contents decreased from April through July, and
      increased from August through December. CONCLUSION: The optimal harvest time is
      determined as from October through December, which corresponds to the traditional
      harvest time.

PMID- 12525116
TI  - [Studies on fatty oils in yolk oil processed by different methods].
AB  - OBJECTIVE: To investigate the influence of different processing methods on fatty
      oils in yolk oil. METHOD: The contents of fatty oils and fatty acids were
      determined by ROESS GOTTILE and GC respectively, and the physicochemical
      properties of fatty oils were identified by pharmacopoeial method. RESULTS AND
      CONCLUSION: The yolk oils processed by daking and dry distillation are almost
      similar in the contents of fatty oils, type of fatty acids, acid value, iodine
      value, saponification value, relative density and refractive index, while obvious
      differences were found in the products processed by chloroform extraction.

PMID- 12525117
TI  - [A-ring formylated flavonoids and oxoaporphinoid alkaloid from Dasymaschalon
      rostratum Merr. et Chun].
AB  - OBJECTIVE: To study the chemical components in the stem of Dasymaschalon
      rostratum. METHOD: The components were extracted with solvent, separated and
      purified with chromatographic methods, identified by NMR, MS, UV, IR and physicol
      chemical constants. RESULTS: Three A-ring-formylated flavonoids and one
      oxoaporphinnoid aikaloid were isolated and identified as lawinal, unonal,
      isounonal and 7-oxodehydroasimilobine. CONCLUSION: All the four compounds were
      isolated for the first time from the genus Dasymaschalon. According to all the
      phytochemistry papers on Annonaceae, A-ring formylated flavonoids in this family
      were isolated from the genus Desmos for the first time. Thus, it is an
      interesting discovery in chemotaxonomy which reveals the close relationship
      between the two genera Desmos and Dasymaschalon.

PMID- 12525118
TI  - [Studies on chemical constituents from Buddleja lindleyana Fert].
AB  - OBJECTIVE: To study the chemical constituents of Buddleja lindleyana. METHOD:
      Separation by chromatographic methods and identification by spectral analysis.
      RESULT: Seven compounds vanillic acid, daidzein octacosanoic acid, beta
      sitosterol-3-O-beta-D-glucopyranoside, stigmasterol-3-O-beta-D-glucopyranoside,
      alpha-spinasterol-3-O-beta-D-glucopyranoside, betulin acid were isolated.
      CONCLUSION: All the compounds were obtained from this plant for the first time.

PMID- 12525119
TI  - [Chemical constituents of Gymnotheca involucrata Pei].
AB  - OBJECTIVE: To study the chemical constituents of Gymnotheca involucrata. METHOD:
      Separating the constituents by means of chromatography and identifying their
      structures on the basis of NMR spectra and TLC with authentic samples. RESULT:
      From the methanolic extract of the whole plant of G. involucrata, three compounds
      were isolated and identified as kaempferol-4',7-dimethyl-3-O-glucoside,
      daucosterol and stigmasterol. CONCLUSION: All the three compounds were isolated
      from this genus for the first time.

PMID- 12525120
TI  - [Studies on chemical constituents in dried buds of Lonicera similis Hemsl].
AB  - OBJECTIVE: To study the chemical constituents in the dried buds of Lonicera
      similis. METHOD: Chromatography and spectral analysis were used to isolate and
      elucidate the constituents. RESULT: Nine compounds were isolated from the dried
      buds of L. similis, and identified as caffeic acid; 3,5-O-dicaffeoylquinic acid;
      chlorogenic acid; palmitic acid; luteolin; quercetin; beta-sitosterol;
      nonacosanol; nonacosane. CONCLUSION: All the compounds were isolated from the
      plant for the first time.

PMID- 12525121
TI  - [Determination of cinnamic acid in Cinnamomum cassia presl after compatibility in
      Coptis chinensis Franch].
AB  - OBJECTIVE: Studying changes of chemical constituents of Cinnamomum cassia after
      compatibility in Coptis chinensis; determining the amount of cinnamic acid in the
      decoction. METHOD: An YWG C18 column was used with a mobile phase of CH3CN-0.01%
      H3PO4(27:73), the flow rate was 1.0 ml.min-1 and the detection wavelength was 280
      nm. RESULT AND CONCLUSION: The calibration curve of cinnamic acid had good linear
      relationship in the range of 0.112-4.48 micrograms. The average recovery was
      100.0%, the relative standard deviation was 0.66%. The amount of cinnamic acid
      was decreased in the decoction, and the decreased degree was related with the
      ratio of C. chinensis to C. cassia.

PMID- 12525122
TI  - [Effects of musk glucoprotein on the function of rat polymorphonuclear leukocytes
      activated by IL-8 in vitro].
AB  - OBJECTIVE: To investigate the effects of musk-1, a glucoprotein component
      isolated from the water extract of musk, on some functions of rat
      polymorphonuclear leukocytes activated by IL-8 in vitro. METHOD: An in vitro
      incubation system was used. Superoxide anion production was determined by
      cytochrome C reduction. beta-glucuronidase and lysozyme release was quantitated
      by enzyme reactions in which phenolph-thaleinglucuronic acid and Micrococcus
      Lysodeikticus were as the substrates, respectively. RESULTS: In comparison with
      control, musk-1 at concentration 1-100 micrograms.ml-1 can increase superoxide
      anion production by 91.7%-291%, and decrease beta-glucuronidase and lysozyme
      release by 2.2%-58.1% and 3.9%-39.8%, respectively. CONCLUSION: Inhibition of
      lysosomel enzyme release might be considered as one of mechanisms of
      antiinflammatory action of musk.

PMID- 12525124
TI  - [Effect of xanthnotoxol on contractility of isolated rabbit ileum].
AB  - OBJECTIVE: To study the effect of Xanthnotoxol on contractility of isolated
      rabbit ileum and its relationship with Ca2+. METHOD: Routine experimental methods
      for isolated ileum were adopted. RESULT: Xanthnotoxol (XT) and Verapamil (Ver)
      inhibited the contraction of isolated rabbit ileum smooth muscle induced by
      submaximal concentrations of acetylcholine (ACh) and serotonim (5-TH), with a
      IC50 value (mumol.L-1) of 10.495 +/- 1.521, 0.428 +/- 0.001 and 18.132 +/- 1.627,
      0.249 +/- 0.003, respectively. XT and Ver inhibited the contraction induced by
      Ca2+ after high K+ depolarization and for noncompetitively antagonist CaCl2
      cumulative dose-response curve, the pD'2 value was 4.69 +/- 0.03 and 6.35 +/-
      0.10, respectively. XT (10 mumol.L-1) and Ver(0.06 mumol.L-1) inhibited the
      contraction induced by ACh in Ca(2+)-free medium, while XT (100 mumol.L-1) but
      not Ver(0.6 mumol.L-1) inhibited the extracellar CA(2+)-dependent contraction
      induced by ACh. CONCLUSION: XT has a calcium-antagonistic effect which was not
      similar to that of Ver.

PMID- 12525123
TI  - [Effect of tianma cuzhi keli (TMCZKL) on contents of transmitter amino acids of
      brain tissue in the mouse repetitious cerebral ischemia reperfusion].
AB  - OBJECTIVE: To research the mechanism of protective action of TMCZKL on brain,
      METHOD: Contents of transmitter amino acids in cortex and hippocampus before and
      after administration of TMCZKL were measured in mice of repetitious cerebral
      ischemia reperfusion. RESULT: The three doses of TMCZKL raised the content of
      glutamic acid in cortex and hippocampus the content of aspartic acid in
      hippocampus and decreased GABA content in cortex significantly. CONCLUSION:
      TMCZKL might antagonize ischemic injury through regulating contents of
      transmitter amino acids and sustain the dynamic equilibrium of EAA and IAA.

PMID- 12525125
TI  - [Preliminary study on apoptosis of human leukemic cells induced by bufalin].
AB  - OBJECTIVE: To study the mechanism of inhibiting actions of bufalin on human
      leukemic cells (HL60). METHODS: HL60 cells were incubated with bufalin at
      different concentrations and growth inhibition was analyzed by trypan-blue
      staining. Cell apoptosis was evaluated by phase contrast microscopy, transmission
      eletron microscopy and agarose gel electrophoresis. RESULTS: Bufalin remarkably
      inhibited the growth of HL60 cells. Apoptosis of HL60 cells could be effectively
      induced by bufalin at concentration of 0.01 mumol.L-1 or higher, showing the
      apoptotic changes in morphology, including cell shrinkage, chromatin
      agglutination and formation of apoptotic corpuscula; DNA cleavage was observed
      with agarose gel electrophoresis. CONCLUSION: Bufalin can effectively induce
      apoptosis of HL60 cells, which is possibly one of the mechanisms for anti-cancer
      of bufalin.

PMID- 12525126
TI  - [Endothelial dysfunction and vascular disease].

PMID- 12525127
TI  - [Diabetic angiopathy: changes in hemostatic and thrombotic functions of the
      endothelium].

PMID- 12525128
TI  - [Role of matrix proteolysis in angiogenesis].

PMID- 12525129
TI  - [Molecular mechanisms of endothelial dysfunction in diabetes].

PMID- 12525130
TI  - [Iron metabolism: new genes for historical diseases].

PMID- 12525131
TI  - [Molecular genetics of hemochromatosis].

PMID- 12525132
TI  - [How to confirm and treat hemochromatosis in 2002?].

PMID- 12525133
TI  - [Diabetes in hemochromatosis].

PMID- 12525134
TI  - [Amino acid metabolism in normal individuals].

PMID- 12525135
TI  - [Insulin, diabetes, and amino acid metabolism].

PMID- 12525136
TI  - [Amino acids and insulin secretion].

PMID- 12525137
TI  - [Regulation of ubiquitin-proteasome dependent muscular proteolysis by hormones
      and nutrients].

PMID- 12525138
TI  - [Protein metabolism in diabetics: new findings on physiopathology and hope about
      therapy].

PMID- 12525139
TI  - [Treatment with portable insulin pump for diabetics in 2002].

PMID- 12525140
TI  - [Freedom-deprived diabetics: management of diabetic subjects under surveillance].

PMID- 12525141
TI  - [Freedom-deprived diabetics. Being a diabetic at the prison of Paris-La Sante].

PMID- 12525142
TI  - [Management of chronic diarrhea in a diabetic patient].

PMID- 12525143
TI  - [Enlarged red legs in diabetics].

PMID- 12525144
TI  - [Epidemiologic findings on sleep apnea syndrome: their value for diabetics].

PMID- 12525145
TI  - [Sleep apnea syndrome: a new cardiovascular risk factor?].

PMID- 12525146
TI  - [Sleep apnea syndrome: socio-professional and medico-legal impact].

PMID- 12525147
TI  - [Sleep apnea syndrome: when to think about it, how to screen it].

PMID- 12525148
TI  - [Sleep apnea syndrome: treatment impact].

PMID- 12525149
TI  - [The Maurice Derot 2002 award. 1971-2002: a story on the insulin receptor].

PMID- 12525150
TI  - Conformational dynamics along an enzymatic reaction pathway: thymidylate
      synthase, "the movie".

PMID- 12525151
TI  - Lessons and conclusions from dissecting the mechanism of a bisubstrate enzyme:
      thymidylate synthase mutagenesis, function, and structure.

PMID- 12525152
TI  - LytG of Bacillus subtilis is a novel peptidoglycan hydrolase: the major active
      glucosaminidase.
AB  - LytG (YubE) of Bacillus subtilis is a novel 32 kDa autolysin produced during
      vegetative growth under the control of Esigma(A) RNA polymerase. Muropeptide
      analysis of vegetative cells of B. subtilis revealed LytG to be the major
      glucosaminidase responsible for peptidoglycan structural determination during
      vegetative growth. Overexpression and purification of LytG allowed its
      biochemical characterization. Despite sequence homology suggesting muramidase
      activity, LytG is a novel glucosaminidase with exoenzyme activity and may form
      part of a novel family of autolysins. It is involved in cell division, lysis, and
      motility on swarm plates.

PMID- 12525153
TI  - A multiply charged tetracaine derivative blocks cyclic nucleotide-gated channels
      at subnanomolar concentrations.
AB  - Cyclic nucleotide-gated (CNG) ion channels are central participants in sensory
      transduction, generating the electrical response to light in retinal
      photoreceptors and to odorants in olfactory receptors. They are expressed in many
      other tissues where their specific roles in signaling remain unclear. As is true
      for many other ion channels, there is a paucity of specific blockers needed to
      dissect the contributions of these channels to cell signaling. CNG channels are
      members of the superfamily of voltage-gated ion channels, and the local
      anesthetic tetracaine is known to block CNG channels in a manner that resembles
      the block of voltage-gated Na(+) channels. The amine in local anesthetics
      interacts with the charged selectivity filter of Na(+) channels, while the
      aromatic ring gets stuck in the inner cavity and has hydrophobic interactions
      with the residues lining that region. Here we have synthesized a derivative of
      tetracaine, 3-[(aminopropyl)amino]-N,N-dimethyl-N-(2-[[4
      (butylamino)benzoyl]oxy]ethyl)propan-1-aminium acetate (APPA-tetracaine), that
      contains three positively charged amines at physiological pH instead of one. This
      compound blocked several different CNG channels in the picomolar to nanomolar
      concentration range at positive membrane potentials, making it several orders of
      magnitude more potent than tetracaine. In contrast, significant block of Na(+)
      channels by APPA-tetracaine required concentrations of hundreds of nanomolar. The
      results suggest that the highly charged moiety of APPA-tetracaine interacts
      strongly with the negative charge cluster in the selectivity filter of CNG
      channels. We propose that a variety of potent and specific ion channel blockers
      could be generated by expanding on traditional blocker structures to target the
      selectivity filters of other channels.

PMID- 12525154
TI  - Identification of amino acids in the nicotinic acetylcholine receptor agonist
      binding site and ion channel photolabeled by 4-[(3-trifluoromethyl)-3H-diazirin-3
      yl]benzoylcholine, a novel photoaffinity antagonist.
AB  - [(3)H]4-[(3-trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine (TDBzcholine) was
      synthesized and used as a photoaffinity probe to map the orientation of an
      aromatic choline ester within the agonist binding sites of the Torpedo nicotinic
      acetylcholine receptor (nAChR). TDBzcholine acts as a nAChR competitive
      antagonist that binds at equilibrium with equal affinity to both agonist sites
      (K(D) approximately 10 microM). Upon UV irradiation (350 nm), nAChR-rich
      membranes equilibrated with [(3)H]TDBzcholine incorporate (3)H into the alpha,
      gamma, and delta subunits in an agonist-inhibitable manner. The specific residues
      labeled by [(3)H]TDBzcholine were determined by N-terminal sequence analysis of
      subunit fragments produced by enzymatic cleavage and purified by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and/or reversed-phase high-performance
      liquid chromatography. For the alpha subunit, [(3)H]TDBzcholine photoincorporated
      into alphaCys-192, alphaCys-193, and alphaPro-194. For the gamma and delta
      subunits, [(3)H]TDBzcholine incorporated into homologous leucine residues,
      gammaLeu-109 and deltaLeu-111. The photolabeling of these amino acids suggests
      that when the antagonist TDBzcholine occupies the agonist binding sites, the Cys
      192-193 disulfide and Pro-194 from the alpha subunit Segment C are oriented
      toward the agonist site and are in proximity to gammaLeu-109/deltaLeu-111 in
      Segment E, a conclusion consistent with the structure of the binding site in the
      molluscan acetylcholine binding protein, a soluble protein that is homologous to
      the nAChR extracellular domain.

PMID- 12525155
TI  - Activation of phospholipase D by bradykinin and sphingosine 1-phosphate in A549
      human lung adenocarcinoma cells via different GTP-binding proteins and protein
      kinase C delta signaling pathways.
AB  - Phospholipase D (PLD) is involved in the signaling by many extracellular ligands,
      and its regulation appears to be quite complex. We investigated the signaling
      pathways initiated by bradykinin (BK) or sphingosine 1-phosphate (S1P) in A549
      cells to define molecular mechanisms responsible for their additive effects on
      PLD activity. BK and S1P each elicited a sustained increase in phosphatidic acid
      content through a rapid and transient activation of PLD. The two pathways
      demonstrated rapid homologous downregulation, but heterologous desensitization
      was not observed. Action of both agonists required protein kinase C (PKC)
      activation and Ca(2+) influx but was mediated by different heterotrimeric G
      proteins. In membranes, inhibition of PKCdelta by rottlerin enhanced BK
      activation of PLD but inhibited that by S1P. Rottlerin inhibited activation of
      PLD in nuclei by both BK and S1P. By in situ immunofluorescence or cell
      fractionation followed by immunoblotting, PLD1 was concentrated primarily in
      nuclei, whereas the membrane fraction contained PLD2 and PLD1. Moreover, PKCdelta
      specifically phosphorylated recombinant PLD2, but not PLD1. BK and S1P similarly
      enhanced RhoA translocation to nuclei, whereas BK was less efficacious than S1P
      on RhoA relocalization to membranes. Effects of both agonists on the nuclear
      fraction, which contains only PLD1, are compatible with a RhoA- and PKCdelta
      dependent process. In membranes, which contain both PLD1 and PLD2, the
      stimulatory effect of S1P on PLD activity can best be explained by RhoA- and
      PKCdelta-dependent activation of PLD1; in contrast, the effects of BK on RhoA
      translocation and enhancement of BK-stimulated PLD activity by PKC inhibition are
      both consistent with PLD2 serving as its primary target.

PMID- 12525156
TI  - Aromatic residues at the extracellular ends of transmembrane domains 5 and 6
      promote ligand activation of the G protein-coupled alpha-factor receptor.
AB  - The alpha-factor receptor (STE2) stimulates a G protein signaling pathway that
      promotes mating of the yeast Saccharomyces cerevisiae. Previous random
      mutagenesis studies implicated residues in the regions near the extracellular
      ends of the transmembrane domains in ligand activation. In this study, systematic
      Cys scanning mutagenesis across the ends of transmembrane domains 5 and 6
      identified two residues, Phe(204) and Tyr(266), that were important for receptor
      signaling. These residues play a specific role in responding to alpha-factor
      since the F204C and Y266C substituted receptors responded to an alternative
      agonist (novobiocin). To better define the structure of this region, the Cys
      substituted mutant receptors were assayed for reactivity with a thiol-specific
      probe that does not react with membrane-imbedded residues. A drop in reactivity
      coincided with residues likely to be buried in the membrane. Interestingly, both
      Phe(204) and Tyr(266) are located very near the interface region. However, these
      assays predict that Phe(204) is accessible at the surface of the receptor,
      consistent with the strong defect in binding alpha-factor caused by mutating this
      residue. In contrast, Tyr(266) was not accessible. This correlates with the
      ability of Y266C mutant receptors to bind alpha-factor and suggests that this
      residue is involved in the subsequent triggering of receptor activation. These
      results highlight the role of aromatic residues near the ends of the
      transmembrane segments in the alpha-factor receptor, and suggest that similar
      aromatic residues may play an important role in other G protein-coupled
      receptors.

PMID- 12525157
TI  - Evidence for structural changes in carboxyl-terminal peptides of transducin alpha
      subunit upon binding a soluble mimic of light-activated rhodopsin.
AB  - Although a high-resolution crystal structure for the ground state of rhodopsin is
      now available, portions of the cytoplasmic surface are not well resolved, and the
      structural basis for the interaction of the cytoplasmic loops with the retinal G
      protein transducin (G(t)) is still unknown. Previous efforts aimed at the design,
      construction, and functional characterization of soluble mimics for the light
      activated state of rhodopsin have shown that grafting defined segments from the
      cytoplasmic region of bovine opsin onto a surface loop in a mutant form of
      thioredoxin (HPTRX) is sufficient to confer partial G(t) activating potential
      [Abdulaev et al. (2000) J. Biol. Chem. 275, 39354-39363]. To assess whether these
      designed mimics could provide a structural insight into the interaction between
      light-activated rhodopsin and G(t), the ability of an HPTRX fusion protein
      comprised of the second (CD) and third (EF) cytoplasmic loops (HPTRX/CDEF) to
      bind G(t) alpha-subunit (G(t)(alpha)) peptides was examined using nuclear
      magnetic resonance (NMR) spectroscopy. Transfer NOESY (TrNOESY) experiments show
      that an 11 amino acid peptide corresponding to the carboxyl terminus of
      G(t)(alpha) (GtP), as well as a "high-affinity" peptide analogue, HAP1, binds to
      HPTRX/CDEF in the fast-exchange regime and undergoes similar, subtle structural
      changes at the extreme carboxyl terminus. Observed TrNOEs suggest that both
      peptides when bound to HPTRX/CDEF adopt a reverse turn that is consistent with
      the C-cap structure that has been previously reported for the interaction of GtP
      with the light-activated signaling state, metarhodopsin II (MII). In contrast,
      TrNOESY spectra provide no evidence for structuring of the amino terminus of
      either GtP or HAP1 when bound to HPTRX/CDEF, nor do the spectra show any
      measurable changes in the CD and EF loop resonances of HPTRX/CDEF, which are
      conformationally dynamic and significantly exchange broadened. Taken together,
      the NMR observations indicate that HPTRX/CDEF, previously identified as a
      functional mimic of MII, is also an approximate structural mimic for this light
      activated state of rhodopsin.

PMID- 12525158
TI  - Hexafluoroisopropanol and acid destabilized forms of apomyoglobin exhibit
      structural differences.
AB  - The conformational properties of partially folded states of apomyoglobin have
      been investigated using an integrated approach based on fluorescence spectroscopy
      and hydrogen/deuterium exchange followed by mass spectrometry. The examined
      states were those obtained: (i) by adding 4% v/v hexafluoroisopropanol to native
      myoglobin, HFIP-MG(N); (ii) by adding 4% v/v hexafluoroisopropanol to acid
      unfolded myoglobin, HFIP-MG(U); (iii) at pH 3.8, I-1 state; and (iv) at pH 2.0
      0.2 M NaCl, A state. Proteolytic digestion of the hydrogen/deuterium exchanged
      proteins showed that, in I-1 state, the helices C, D, E, and F incorporate more
      deuterium, whereas in HFIP-MG(N) the exchange rate is similar for all protein
      regions. These results suggest that I-1 contains the ABGH domain in a native-like
      organization, whereas HFIP-MG(N) loses a large number of tertiary interactions,
      thus acquiring a more flexible structure. The fluorescence data are consistent
      with the above picture. In fact, the tryptophan/ANS energy transfer is much less
      efficient for the ANS-HFIP-MG(N) complex than for the other complexes, thus
      suggesting that the distances between the fluorophores might be increased.
      Moreover, fluorescence polarization measurements indicated that the rotational
      motion of HFIP-MG(N) occurs on a longer time scale than the other partially
      folded states, thus suggesting that the volume of this state could be larger. The
      overall results indicate that addition of hexafluoroisopropanol to native
      myoglobin results in the formation of a true molten globule where tertiary
      interactions are reduced, while the secondary structure and the globular
      compactness are conserved.

PMID- 12525159
TI  - Backbone dynamics of reduced plastocyanin from the cyanobacterium Anabaena
      variabilis: regions involved in electron transfer have enhanced mobility.
AB  - The dynamics of the backbone of the electron-transfer protein plastocyanin from
      the cyanobacterium Anabaena variabilis were determined from the (15)N and
      (13)C(alpha) R(1) and R(2) relaxation rates and steady-state [(1)H]-(15)N and
      [(1)H]-(13)C nuclear Overhauser effects (NOEs) using the model-free approach. The
      (13)C relaxation studies were performed using (13)C in natural abundance.
      Overall, it is found that the protein backbone is rigid. However, the regions
      that are important for the function of the protein show moderate mobility
      primarily on the microsecond to millisecond time scale. These regions are the
      "northern" hydrophobic site close to the metal site, the metal site itself, and
      the "eastern" face of the molecule. In particular, the mobility of the latter
      region is interesting in light of recent findings indicating that residues also
      on the eastern face of plastocyanins from prokaryotes are important for the
      function of the protein. The study also demonstrates that relaxation rates and
      NOEs of the (13)C(alpha) nuclei of proteins are valuable supplements to the
      conventional (15)N relaxation measurements in studies of protein backbone
      dynamics.

PMID- 12525160
TI  - Helix packing in subunit a of the Escherichia coli ATP synthase as determined by
      chemical labeling and proteolysis of the cysteine-substituted protein.
AB  - Subunit a of the Escherichia coli ATP synthase is thought to control access of
      protons to the ring of c subunits during proton-driven ATP synthesis. In this
      study, the surface exposure of subunit a in the periplasm has been examined using
      3-N-maleimidyl-propionyl biocytin labeling in cells permeabilized by polymyxin B
      nonapeptide, and the helix packing at the periplasmic surface has been probed by
      metal-chelate mediated proteolysis. Eighteen residues between 119 and 146 were
      changed individually to cysteine and tested for accessibility. Positions labeled
      included D124 and D146, indicating a periplasmic loop of at least 23 amino acids.
      Residues near the ends of the transmembrane spans were tested with 5-(alpha
      bromoacetamido)-1,10-phenanthroline-copper for chemical proteolysis. Only
      residues W241C and D44C, and to a lesser extent I43C, led to proteolytic
      fragments after oxidation. The fragments were sized by comparison with molecular
      weight standards generated by Factor Xa sites engineered into subunit a.
      Fragments were detected by immunoblotting using an engineered HA epitope at the
      carboxyl-terminal end of subunit a. The results indicated that both transmembrane
      span 5 (W241) and transmembrane span 1 (D44) are close to transmembrane span 2.

PMID- 12525161
TI  - Interaction of the mitotic inhibitor monastrol with human kinesin Eg5.
AB  - The microtubule-dependent kinesin-like protein Eg5 from Homo sapiens is involved
      in the assembly of the mitotic spindle. It shows a three-domain structure with an
      N-terminal motor domain, a central coiled coil, and a C-terminal tail domain. In
      vivo HsEg5 is reversibly inhibited by monastrol, a small cell-permeable molecule
      that causes cells to be arrested in mitosis. Both monomeric and dimeric Eg5
      constructs have been examined in order to define the minimal monastrol binding
      domain on HsEg5. NMR relaxation experiments show that monastrol interacts with
      all of the Eg5 constructs used in this study. Enzymatic techniques indicate that
      monastrol partially inhibits Eg5 ATPase activity by binding directly to the motor
      domain. The binding is noncompetitive with respect to microtubules, indicating
      that monastrol does not interfere with the formation of the motor-MT complex. The
      binding is not competitive with respect to ATP. Both enzymology and in vivo
      assays show that the S enantiomer of monastrol is more active than the R
      enantiomer and racemic monastrol. Stopped-flow fluorometry indicates that
      monastrol inhibits ADP release by forming an Eg5-ADP-monastrol ternary complex.
      Monastrol reversibly inhibits the motility of human Eg5. Monastrol has no
      inhibitory effect on the following members of the kinesin superfamily: MC5
      (Drosophila melanogaster Ncd), HK379 (H. sapiens conventional kinesin), DKH392
      (D. melanogaster conventional kinesin), BimC1-428 (Aspergillus nidulans BimC),
      Klp15 (Caenorhabditis elegans C-terminal motor), or Nkin460GST (Neurospora crassa
      conventional kinesin).

PMID- 12525162
TI  - Features in short guanine-rich sequences that stimulate DNA polymerization in
      vitro.
AB  - We have discovered that short guanine-rich oligonucleotides are able to self
      associate into higher order structures that stimulate DNA synthesis in vitro
      without the addition of a conventional template [Ying, J., Bradley, R. K., Jones,
      L. B., Reddy, M. S., Colbert, D. T., Smalley, R. E., and Hardin, S. H. (1999)
      Biochemistry 38, 16461-16468]. Our initial analysis indicated the importance of
      the presence of three contiguous guanines (G) in an oligonucleotide that
      stimulates DNA polymerization. To gain insight into and to refine sequence
      requirements for the unexpected DNA synthesis, we analyzed a 231-member guanine
      rich octamer library in a fluorescent nucleotide polymerization assay. We observe
      that, in addition to three contiguous Gs, the presence of a secondary G cluster
      within the octamer is essential. Furthermore, the location of the primary G
      cluster in the center of the molecule is most stimulatory. The majority of the
      octamers that form extended DNA products have a single non-G base separating the
      primary and secondary G clusters, the identity of which is predominantly thymine
      (T). Further, a T 5' or 3' of the primary G cluster positively influences the
      stimulatory function of the oligonucleotide. Overall, the occurrence of bases in
      the octamer is in the descending order of G > T > A > C. Our studies demonstrate
      that structures stabilized by noncanonical base pairings are recognized by a DNA
      polymerase in vitro, and these findings may have relevance within the cell. In
      particular, the features of these G-rich stimulatory sequences show striking
      similarities to telomeric sequences that form diverse G-quartet structures in
      vitro.

PMID- 12525163
TI  - Hydrogen exchange in a large 29 kD protein and characterization of molten globule
      aggregation by NMR.
AB  - The nature of denatured ensembles of the enzyme human carbonic anhydrase (HCA)
      has been extensively studied by various methods in the past. The protein
      constitutes an interesting model for folding studies that does not unfold by a
      simple two-state transition, instead a molten globule intermediate is highly
      populated at 1.5 M GuHCl. In this work, NMR and H/D exchange studies have been
      conducted on one of the isozymes, HCA I. The H/D exchange studies, which were
      enabled by the previously obtained resonance assignment of HCA I, have been used
      to identify unfolded forms that are accessible from the native state. In
      addition, the GuHCl-induced unfolded states of HCA I have also been characterized
      by NMR at GuHCl concentrations in the 0-5 M range. The most important findings in
      this work are as follows: (1) Amide protons located in the center of the beta
      sheet require global unfolding events for efficient H/D exchange. (2) The molten
      globule and the native state give similar protection against H/D exchange for all
      of the observable amide protons (i.e., water seems not to efficiently penetrate
      the interior of the molten globule). (3) At high protein concentrations, the
      molten globule can form large aggregates, which are not detectable by solution
      state NMR methods. (4) The unfolded state (U), present at GuHCl concentrations
      above 2 M, is composed of an ensemble of conformations having residual structures
      with different stabilities.

PMID- 12525164
TI  - In vitro characterization of lactoferrin aggregation and amyloid formation.
AB  - Lactoferrin has previously been identified in amyloid deposits in the cornea,
      seminal vesicles, and brain. We report in this paper a highly amyloidogenic
      region of lactoferrin (sequence of NAGDVAFV). This region was initially
      identified by sequence comparison with medin, a 5.5 kDa amyloidogenic fragment
      derived from lactadherin. Subsequent characterization revealed that this peptide
      forms amyloid fibrils at pH 7.4 when incubated at 37 degrees C. Furthermore,
      although full-length lactoferrin does not by itself form amyloid fibrils, the
      protein does bind to the peptide fibrils as revealed by an increase in thioflavin
      T fluorescence and the presence of enlarged fibrils by transmission electron
      microscopy and polarized light microscopy. The binding of lactoferrin is a
      selective interaction with the NAGDVAFV fibrils. Lactoferrin does not bind to
      insulin or lysozyme fibrils, and the NAGDVAFV fibrils do not bind to soluble
      insulin or lysozyme. The lactoferrin appears to coat the peptide fibril surface
      to form mixed peptide/protein fibrils, but again there is no evidence for the
      formation of lactoferrin-only fibrils. This interaction, therefore, seems to
      involve selective binding rather than conventional seeding of fibril formation.
      We suggest that such a process could be generally important in the formation of
      amyloid fibrils in vivo since the identification of both full-length protein and
      protein fragments is common in ex vivo amyloid deposits.

PMID- 12525165
TI  - Crystal structures of human prostatic acid phosphatase in complex with a
      phosphate ion and alpha-benzylaminobenzylphosphonic acid update the mechanistic
      picture and offer new insights into inhibitor design.
AB  - The X-ray crystal structure of human prostatic acid phosphatase (PAP) in complex
      with a phosphate ion has been determined at 2.4 A resolution. This structure
      offers a snapshot of the final intermediate in the catalytic mechanism and does
      not support the role of Asp 258 as a proton donor in catalysis. A total of eight
      hydrogen bonds serve to strongly bind the phosphate ion within the active site.
      Bound PEG molecules from the crystallization matrix have allowed the
      identification of a channel within the molecule that likely plays a role in
      molecular recognition and in macromolecular substrate selectivity. Additionally,
      the structure of PAP in complex with a phosphate derivative, alpha
      benzylaminobenzylphosphonic acid, a potent inhibitor (IC(50) = 4 nM), has been
      determined to 2.9 A resolution. This structure gives new insight into the
      determinants of binding hydrophobic ligands within the active site and allows us
      to explain PAP's preference for aromatic substrates.

PMID- 12525166
TI  - Temperature and ligand dependence of conformation and helical order in myosin
      filaments.
AB  - Mammalian myosin filaments are helically ordered only at higher temperatures (>20
      degrees C) and become progressively more disordered as the temperature is
      decreased. It had previously been suggested that this was a consequence of the
      dependence of the hydrolytic step of myosin ATPase on temperature and the
      requirement that hydrolysis products (e.g., ADP.P(i)) be bound at the active
      site. An alternative hypothesis is that temperature directly affects the
      conformation of the myosin heads and that they need to be in a particular
      conformation for helical order in the filament. To discriminate between these two
      hypotheses, we have studied the effect of temperature on the helical order of
      myosin heads in rabbit psoas muscle in the presence of nonhydrolyzable ligands.
      The muscle fibers were overstretched to nonoverlap such that myosin affinity for
      nucleotides was not influenced by the interaction of myosin with the thin
      filament. We show that with bound ADP.vanadate, which mimics the transition state
      between ATP and hydrolysis products, or with the ATP analogues AMP-PNP or
      ADP.BeF(x)() the myosin filaments are substantially ordered at higher
      temperatures but are reversibly disordered by cooling. These results reinforce
      recent studies in solution showing that temperature as well as ligand influence
      the equilibrium between multiple myosin conformations [Malnasi-Csizmadia, A.,
      Pearson, D. S., Kovacs, M., Woolley, R. J., Geeves, M. A., and Bagshaw, C. R.
      (2001) Biochemistry 40, 12727-12737; Malnasi-Csizmadia, A., Woolley, R. J., and
      Bagshaw, C. R. (2000) Biochemistry 39, 16135-16146; Urbanke, C., and Wray, J.
      (2001) Biochem. J. 358, 165-173] and indicate that helical order requires the
      myosin heads to be in the closed conformation. Our results suggest that most of
      the heads in the closed conformation are ordered, and that order is not produced
      in a separate step. Hence, helical order can be used as a signature of the closed
      conformation in relaxed muscle. Analysis of the dependence on temperature of
      helical order and myosin conformation shows that in the presence of these
      analogues one ordered (closed) conformation and two disordered conformations with
      distinct thermodynamic properties coexist. Low temperatures favor one disordered
      conformation, while high temperatures favor the ordered (closed) conformation
      together with a second disordered conformation.

PMID- 12525167
TI  - Enhanced membrane permeabilization and antibacterial activity of a disulfide
      dimerized magainin analogue.
AB  - A cysteine substitution analogue of magainin-2 amide (magainin-F12W, N22C;
      denoted here as mag-N22C), and a disulfide-linked dimer prepared by air oxidation
      [(mag-N22C)(2)], were compared in their ability to release carboxyfluorescein
      (CF) from 100-nm large unilamellar vesicles (LUV) and to kill the Gram negative
      bacteria Stenotrophomonas maltophilia and Escherichia coli. The disulfide
      dimerized peptide showed enhanced permeabilization and antimicrobial activity,
      when compared with the monomeric peptide, that was particularly marked at very
      low peptide concentrations. The enhanced CF-releasing activity of the dimer at
      low concentrations in vesicles results from (i) enhanced binding to negatively
      charged membrane surfaces and (ii) a low concentration dependence for
      permeabilization in the dimer compared to the monomer. The unique properties of
      the dimeric peptide suggest a role for structural diversity of antimicrobial
      peptides in frog skin, including the recent identification of a heterodimer
      composed of disulfide-linked amphipathic helical peptides [Batista et al. (2001)
      FEBS Lett. 494, 85-89]. Disulfide-dimerization of pore-forming, positively
      charged, amphipathic helical peptides may be a useful general approach to the
      generation of peptide antimicrobials having activity at very low concentrations.

PMID- 12525168
TI  - Osmosensor ProP of Escherichia coli responds to the concentration, chemistry, and
      molecular size of osmolytes in the proteoliposome lumen.
AB  - Transporter ProP of Escherichia coli mediates the cellular accumulation of
      organic zwitterions in response to increased extracellular osmolality. We
      compared and characterized the osmoregulation of ProP activity in cells and
      proteoliposomes to define the osmotic shift-induced cellular change(s) to which
      ProP responds. ProP-(His)(6) activity in cells and proteoliposomes was correlated
      with medium osmolality, not osmotic shift, turgor pressure, or membrane strain.
      Both K(M) and V(max) for proline uptake via ProP-(His)(6) increased with
      increasing medium osmolality, as would be expected if osmolality controls the
      proportions of transporter with inactive and active conformations. The osmolality
      yielding half-maximal ProP-(His)(6) activity was higher in proteoliposomes than
      in cells. The osmolality response of ProP is also attenuated in bacteria lacking
      soluble protein ProQ. Indeed, the catalytic constant (k(cat)) for ProP-(His)(6)
      in proteoliposomes approximated that of ProP in intact bacteria lacking ProQ.
      Thus, the proteoliposome system may replicate a primary osmosensory response that
      can be further amplified by ProQ. ProP-(His)(6) is designated as an osmosensor
      because its activity is dependent on the osmolality, but not the composition, of
      the assay medium to which the cell surface is exposed. In contrast, ProP-(His)(6)
      activity was dependent on both the osmolality and the composition of the lumen in
      osmolyte-loaded proteoliposomes. For proteoliposomes containing inorganic salts,
      glucose, or poly(ethylene glycol) 503, transporter activity correlated with total
      lumenal cation concentration. In contrast, for proteoliposomes loaded with larger
      poly(ethylene glycol)s, the osmolality, the lumenal cation concentration, and the
      lumenal ionic strength at half-maximal transporter activity decreased
      systematically with poly(ethylene glycol) radius of gyration (range 0.8-1.8 nm).
      These data suggest that ProP-(His)(6) responds to osmotically induced changes in
      both cytoplasmic K(+) levels and the concentration of cytoplasmic macromolecules.

PMID- 12525169
TI  - Application of a novel analysis to measure the binding of the membrane
      translocating peptide penetratin to negatively charged liposomes.
AB  - The binding of penetratin, a peptide that has been found useful for cellular
      delivery of large hydrophilic molecules, to negatively charged vesicles was
      investigated. The surface charge density of the vesicles was varied by mixing
      zwitterionic dioleoylphosphatidylcholine (DOPC) and negatively charged
      dioleoylphosphatidylglycerol (DOPG) at various molar ratios. The extent of
      membrane association was quantified from tryptophan emission spectra recorded
      during titration of peptide solution with liposomes. A singular value
      decomposition of the spectral data demonstrated unambiguously that two species,
      assigned as peptide free in solution and membrane-bound peptide, respectively,
      account for the spectral data of the titration series. Binding isotherms were
      then constructed by least-squares projection of the titration spectra on
      reference spectra of free and membrane-bound peptide. A model based on the Gouy
      Chapman theory in combination with a two-state surface partition equilibrium,
      separating the electrostatic and the hydrophobic contributions to the binding
      free energy, was found to be in excellent agreement with the experimental data.
      Using this model, a surface partition constant of approximately 80 M(-)(1) was
      obtained for the nonelectrostatic contribution to the binding of penetratin
      irrespective of the fraction of negatively charged lipids in the membrane,
      indicating that the hydrophobic interactions are independent of the surface
      charge density. In accordance with this, circular dichroism measurements showed
      that the secondary structure of membrane-associated penetratin is independent of
      the DOPC/DOPG ratio. Experiments using vesicles with entrapped carboxyfluorescein
      showed that penetratin does not form membrane pores. Studies of the cationic
      peptide penetratin are complicated by extensive adsorption to surfaces of quartz
      and plastics. By modification of the quartz cell walls with the cationic polymer
      poly(ethylenimine), the peptide adsorption was reduced to a tolerable level. The
      data analysis method used for construction of the binding isotherms eliminated
      errors emanating from the remaining peptide adsorption, which otherwise would
      prevent a proper quantification of the binding.

PMID- 12525170
TI  - The limits of promiscuity: isoform-specific dimerization of filamins.
AB  - Filamins are a family of actin cross-linking proteins that are primarily
      localized in the cortical cytoplasm of all mammalian cells. Until now, three
      major isoforms (filamins a, b, and c) have been identified, that were shown to be
      differentially expressed and/or localized in different tissues. An amino-terminal
      double CH-domain actin binding domain, and a dimerization region in the carboxy
      terminal portion of the protein are the molecular basis for its actin cross
      linking activity. Chemical cross-linking of bacterially expressed recombinant
      proteins was used to demonstrate that in all three filamin isoforms the most
      carboxy-terminally situated immunoglobulinlike domain is required and sufficient
      for dimerization. The efficiency of the dimerization was increased upon inclusion
      of the preceding hinge 2 region, indicating a function for this region in the
      regulation of dimerization. By mixing recombinant proteins derived from different
      filamin isoforms, we found that heterodimer formation is possible between
      filamins b and c but not between filamin a and the other two filamins. This
      selectivity of dimerization might provide a further molecular explanation for the
      differential intracellular sorting of filamin isoforms and their distinct
      properties.

PMID- 12525171
TI  - Fourier transform infrared spectroscopic study of the interactions of a strongly
      antimicrobial but weakly hemolytic analogue of gramicidin S with lipid micelles
      and lipid bilayer membranes.
AB  - Cyclo[VKLdKVdYPLKVKLdYP] (GS14dK(4)), a synthetic tetradecameric ring-size
      analogue of the naturally occurring antimicrobial peptide gramicidin S (GS),
      retains the strong antimicrobial activity of GS but is 15-20 times less
      hemolytic. To characterize its interaction with lipid membranes and to understand
      the molecular basis of its capacity to lyse bacterial cells, in preference to
      erythrocytes, we have investigated the interactions of GS14dK(4) with detergent
      micelles and with lipid bilayer model membranes by Fourier transform infrared
      spectroscopy and compared our results with those of a similar study of GS [Lewis,
      R. N. A. H., et al. (1999) Biochemistry 38, 15193-15203]. In both aqueous and
      organic solvent solutions, GS14dK(4) adopts a beta-sheet conformation that is
      somewhat distorted and more sensitive to the polarity of its environment than GS.
      Like GS, GS14dK(4) is completely or partially excluded from gel-state lipid
      bilayers but interacts strongly with liquid-crystalline lipid bilayers and
      detergent micelle, and interacts more strongly with more fluid liquid-crystalline
      lipid systems. However, its interactions are more strongly influenced by membrane
      lipid order and fluidity, and unlike GS, it is essentially excluded from
      cholesterol-containing phospholipid bilayers. Also, GS14dK(4) is excluded from
      cationic lipid bilayers, but partitions more strongly and/or penetrates more
      deeply into anionic lipid bilayers than into those composed of either
      zwitterionic or nonionic lipids. Anionic lipids also facilitate GS14dK(4)
      interactions with multicomponent lipid bilayers which are predominantly
      zwitterionic or nonionic. Although GS14dK(4) generally penetrates and/or
      partitions into zwitterionic or uncharged lipid bilayers less strongly than does
      GS, its greater size and altered distribution of positive charges make it
      intrinsically more perturbing with regard to membrane organization once
      associated with lipid bilayers. This fact, combined with its relatively strong
      interactions with anionic phospholipids, may explain why GS14dK(4) retains
      relatively high antimicrobial activity. However, its low hemolytic activity is
      probably largely attributable to its low propensity to penetrate and/or partition
      into cholesterol-containing zwitterionic lipid membranes.

PMID- 12525173
TI  - Exploring peptide membrane interaction using surface plasmon resonance:
      differentiation between pore formation versus membrane disruption by lytic
      peptides.
AB  - Lytic peptides comprise a large group of membrane-active peptides used in the
      defensive and offensive systems of all organisms. Differentiating between their
      modes of interaction with membranes is crucial for understanding how these
      peptides select their target cells. Here we utilized SPR to study the interaction
      between lytic peptides and lipid bilayers (L1 sensor chip). Using studies also on
      hybrid monolayers (HPA sensor chip) revealed that SPR is a powerful tool for
      obtaining a real-time monitoring of the steps involved in the mode of action of
      membrane-active peptides, some of which previously could not be detected directly
      by other techniques and reported here for the first time. We investigated the
      mode of action of peptides that represent two major families: (i) the bee venom,
      melittin, as a model of a non-cell-selective peptide that forms transmembrane
      pores and (ii) magainin and a diastereomer of melittin (four amino acids were
      replaced by their D enantiomers), as models of bacteria-selective non-pore
      forming peptides. Fitting the SPR data to different interaction models allows
      differentiating between two major steps: membrane binding and membrane insertion.
      Melittin binds to PC/cholesterol approximately 450-fold better than its
      diastereomer and magainin, mainly because it is inserted into the inner leaflet
      (2/3 of the binding energy), whereas the other two are not. In contrast, there is
      only a slight difference in the binding of all the peptides to negatively charged
      PE/PG mono- and bilayer membranes (in the first and second steps), indicating
      that the inner leaflet contributes only slightly to their binding to PE/PG
      bilayers. Furthermore, the 100-fold stronger binding of the cell-selective
      peptides to PE/PG as compared with PC/cholesterol resulted only from
      electrostatic attraction to the negatively charged headgroups of the outer
      leaflet. These results clearly differentiate between the two general mechanisms:
      pore formation by melittin only in zwitterionic membranes and a detergent-like
      effect (carpet mechanism) for all the peptides in negatively charged membranes,
      in agreement with their biological function.

PMID- 12525172
TI  - Polycystin-2 interacts with troponin I, an angiogenesis inhibitor.
AB  - Polycystin-2 (PC2), encoded by the PKD2 gene, is mutated in 10-15% of autosomal
      dominant polycystic kidney disease (ADPKD) patients. PC2 is a Ca(2+)-permeable
      nonselective cation channel and is present in kidney and many other organs.
      Likewise, PKD2-mutated patients and mice exhibit extrarenal abnormalities. In
      comparison with cysts in the kidney, liver, and pancreas, abnormalities in the
      heart, brain, and vascular vessels are less understood. In particular, roles of
      PC2 in muscle and endothelia remain largely unknown. In the present study, using
      a yeast two-hybrid screening, we discovered that the PC2 carboxyl terminal domain
      (D682-V968) interacts with the cardiac troponin I, an important regulatory
      component of the actin microfilament in cardiac muscle cells. This interaction
      was demonstrated by GST pull-down and microtiter binding assays. Dose-dependent
      binding between PC2 and troponin I followed a Michaelis-Menten relationship,
      indicating a 1:1 binding stoichiometry. The interacting domains were located to
      the R872-H927 segment of PC2 and the M1-V107 and K106-L158 segments of troponin
      I. Co-immunoprecipitation experiments demonstrated that the cardiac and two
      skeletal isoforms of troponin I were all associated with PC2, when coexpressed in
      mouse fibroblast NIH 3T3 cells and Xenopus oocytes. Furthermore, reciprocal co
      immunoprecipitation verified the interaction between the native polycystin-2 and
      troponin I in human adult heart tissues. This study thus provides new evidence
      for a direct attachment of PC2 to the actin microfilament network, in addition to
      the recently identified association between PC2 and trypomyosin-1. Troponin I
      functions as an inhibitory subunit of the troponin complex for calcium-dependent
      regulation of muscle contraction and as an inhibitor of angiogenesis seen in
      ADPKD. It is possible that altered interaction due to pathogenic polycystin-1 or 
      2 mutations can account for angiogenesis in ADPKD and may be corrected to some
      extent by exogenous troponin I.

PMID- 12525174
TI  - Conserved residues R420 and Q428 in a cytoplasmic loop of the citrate/malate
      transporter CimH of Bacillus subtilis are accessible from the external face of
      the membrane.
AB  - CimH of Bacillus subtilis is a secondary transporter for citrate and malate that
      belongs to the 2-hydroxycarboxylate transporter (2HCT) family. Conserved residues
      R143, R420, and Q428, located in putative cytoplasmic loops and R432, located at
      the cytoplasmic end of the C-terminal transmembrane segment XI were mutated to
      Cys to identify residues involved in binding of the substrates. R143C, R420C, and
      Q428C revealed kinetics similar to those of the wild-type transporter, while the
      activity of R432C was reduced by at least 2 orders of magnitude. Conservative
      replacement of R432 with Lys reduced the activity by 1 order of magnitude, by
      lowering the affinity for the substrate 10-fold. It is concluded that the
      arginine residue at position 432 in CimH interacts with one of the carboxylate
      groups of the substrates. Labeling of the R420C and Q428C mutants with thiol
      reagents inhibited citrate transport activity. Surprisingly, the cysteine
      residues in the cytoplasmic loops in both R420C and Q428C were accessible to the
      small, membrane-impermeable, negatively charged MTSES reagent from the external
      site of the membrane in a substrate protectable manner. The membrane impermeable
      reagents MTSET,(1) which is positively charged, and AMdiS, which is negatively
      charged like MTSES but more bulky, did not inhibit R420C and Q428C. It is
      suggested that the access pathway is optimized for small, negatively charged
      substrates. Either the cytoplasmic loop containing residues R420 and Q428 is
      partly protruding to the outside, possibly in a reentrant loop like structure, or
      alternatively, a water-filled substrate translocation pathway extents to the
      cytoplasm-membrane interface.

PMID- 12525175
TI  - Probing the role of backbone hydrogen bonding in beta-amyloid fibrils with
      inhibitor peptides containing ester bonds at alternate positions.
AB  - Protein-protein interactions are frequently mediated by stable, intermolecular
      beta-sheets. A number of cytokines and the HIV Protease, for example, dimerize
      through beta-sheet motifs. Evidence also suggests that the macromolecular
      assemblies of peptides and proteins in amyloid fibrils are stabilized by
      intermolecular beta-sheets. In this paper, we report that interfering with the
      backbone hydrogen bonding of an amyloidgenic peptide (Abeta16-20) by replacing
      amide bonds with ester bonds prevents the aggregation of the peptide. The ester
      bonds were incorporated in an alternating fashion so that the peptide presents
      two unique hydrogen bonding faces when arrayed in an extended, beta-strand
      conformation; one face of the peptide has normal hydrogen bonding capabilities,
      but the other face is missing amide protons and its ability to hydrogen bond is
      severely limited. Analytical ultracentrifugation experiments demonstrate that
      this ester peptide, Abeta16-20e, is predominantly monomeric under solution
      conditions, unlike the fibril-forming Abeta16-20 peptide. Abeta16-20e also
      inhibits the aggregation of the Abeta1-40 peptide and disassembles preformed
      Abeta1-40 fibrils. These results suggest that backbone hydrogen bonding is
      critical for the assembly of amyloid fibrils.

PMID- 12525176
TI  - Mechanism of formin-induced nucleation of actin filaments.
AB  - A fragment of the yeast formin Bni1 containing the FH1FH2 domains increases the
      rate of filament nucleation from pure G-actin [Pruyne et al. (2002) Science 297,
      612-615]. To determine the mechanism of nucleation, we compared the G-actin
      dependence of Bni1FH1FH2-induced polymerization with theoretical models. The data
      best fit a model suggesting that Bni1FH1FH2 stabilizes an actin dimer. We also
      show that nucleation increases with the square root of the Bni1FH1FH2
      concentration. We demonstrate that this relationship is expected for any such
      nucleator, independent of nucleus size. The proline-rich FH1 domain binds
      profilin, and deletion of this domain decreases the contribution of profilin
      actin to the nucleation. A role for profilin binding to the FH1 domain in
      filament nucleation was supported by the inability of Bni1FH1FH2 to utilize a
      mutant profilin, H133S profilin, with defective binding to polyproline.
      Bni1FH1FH2 partially inhibits barbed-end elongation, and we find that the rate
      constants for both polymerization and depolymerization are decreased by
      approximately 50%. Bni1FH1FH2 has no effect on pointed-end kinetics or on the
      critical concentration. To investigate the domains of Bni1 required for these
      activities, the experiments were all duplicated with the FH2 domain alone. The
      FH2 domain is as effective as the FH1FH2 domains together in inhibiting barbed
      end kinetics; it is less effective as a nucleator but the mechanism is again best
      fit by dimer stabilization.

PMID- 12525177
TI  - Allosteric binding properties of a monoclonal antibody and its Fab fragment.
AB  - Detailed equilibrium binding studies were conducted on a monoclonal antibody
      directed against Pb(II) complexed with a protein conjugate of
      diethylenetriaminepentaacetic acid (DTPA). Binding curves obtained with DTPA and
      a cyclohexyl derivative of DTPA in the presence and absence of metal ions were
      consistent with the anticipated one-site homogeneous binding model. Binding
      curves obtained with aminobenzyl-DTPA or its complexes with Ca(II), Sr(II), and
      Ba(II) were highly sigmoidal, characterized by Hill coefficients of 2.3-6.5.
      Binding curves obtained with the Pb(II) and In(III) complexes of aminobenzyl-DTPA
      were hyperbolic, but in each case the apparent affinity of the antibody for the
      chelator-metal complex was higher in the presence of excess chelator than it was
      in the presence of excess metal ion. In the presence of excess chelator, the
      equilibrium dissociation constant for the binding of aminobenzyl-DTPA-Pb(II) to
      the antibody was 9.5 x 10(-)(10) M. Binding curves obtained with the Hg(II) and
      Cd(II) complexes of aminobenzyl-DTPA were biphasic, indicative of negative
      cooperativity. Further binding studies demonstrated that aminobenzyl-DTPA-Hg(II)
      opposed the binding of additional chelator-metal complexes to the antibody more
      strongly than did aminobenzyl-DTPA-Cd(II). The Fab fragment differed from the
      intact antibody only in that the apparent affinity of the Fab was generally lower
      for a given chelator-metal complex. These data are interpreted in terms of a
      model in which (i) aminobenzyl-DTPA and its complexes bind both to the antigen
      binding site and to multiple charged sites on the surface of the compact
      immunoglobulin; and (ii) the bound, highly charged ligands interact in a
      complicated fashion through the apolar core of the folded antibody.

PMID- 12525178
TI  - Subunit dissociation, unfolding, and inactivation of bothrojaracin, a C-type
      lectin-like protein from snake venom.
AB  - Snake venoms contain a large number of hemostatically active proteins that are
      structurally related to Ca(2+)-dependent animal lectins. These proteins, called C
      type lectin-like proteins (CLPs), are generally found as heterodimers composed of
      two homologous subunits linked by a disulfide bond. Here, bothrojaracin (BJC), a
      CLP from Bothrops jararaca venom that is also a thrombin inhibitor, has been used
      as a model to study the subunit dissociation and unfolding of CLPs from snake
      venom. Dithiothreitol (DTT) up to 10 mM produces minor effects on the tertiary
      structure and activity of BJC. On the other hand, chromatographic studies and
      fluorescence polarization measurements indicate that the interchain disulfide
      bond is disrupted by DTT, although the dimeric association is maintained.
      Treatment of BJC with urea produces a progressive red shift in the emission
      spectra of the tryptophan residues, and circular dichroism measurements show that
      BJC retains significant secondary structure in the presence of 8 M urea,
      suggesting only partial unfolding. The effects of urea are fully reversible, as
      there is complete recovery of BJC activity after removal of the denaturing agent.
      Addition of DTT to a protein sample previously treated with 8 M urea produces a
      slightly larger spectral shift than that observed with urea alone. Furthermore,
      in this condition BJC loses its secondary structure, and its subunits are
      dissociated. After removal of urea and DTT, BJC is inactive toward thrombin,
      suggesting the irreversibility of their combined action. Altogether, our data
      show that (i) BJC is highly resistant to urea or DTT effects, requiring the
      simultaneous action of both agents to fully denature the protein, and (ii) BJC
      monomers are tightly associated, and the presence of DTT combined with high urea
      concentrations is necessary to disrupt them. On the basis of these results we
      propose the first denaturation model for a CLP from snake venom.

PMID- 12525179
TI  - The unusual catalytic triad of poliovirus protease 3C.
AB  - Picornaviruses are small pathogen RNA viruses, like poliovirus, hepatitis A
      virus, rhinovirus, and others. They produce a large polyprotein, which is cleaved
      by virally encoded cysteine peptidases, picornains 2A and 3C. Picornain 3C
      represents an intermediate between the serine peptidase chymotrypsin and the
      cysteine peptidase papain. Its steric structure resembles chymotrypsin, but its
      nucleophile is a thiol instead of the hydroxyl group. The histidine is a general
      base catalyst in chymotrypsin but forms a thiolate-imidazolium ion pair in
      papain. The third member of the catalytic triad is an acid (Glu71) as in
      chymotrypsin rather than an amide found in papain. Transformation of poliovirus
      3C peptidase into a serine peptidase results in lower activity by a factor of
      430, but the activity extends toward higher pH with the more basic hydroxyl
      group. The decrease in activity is caused by the less ordered active site, as
      supported by the unfavorable entropy of activation. At 25 degrees C the
      specificity rate constant for the thiol enzyme approaches k(1), the rate constant
      for the formation of the enzyme-substrate complex, but k(2), the acylation
      constant, becomes predominant with the increase in temperature. In contrast, for
      the serine peptidase the specificity constant is less than k(1) over the entire
      temperature range, and the transition state is controlled by both k(1) and k(2).
      The acidic component of the catalytic triad is essential for activity, but its
      negative charge does not influence the ionization of the thiol group.

PMID- 12525180
TI  - Protochlorophyllide oxidoreductase: "dark" reactions of a light-driven enzyme.
AB  - The light-driven enzyme NADPH:protochlorophyllide oxidoreductase (POR) catalyzes
      the reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide), a key
      regulatory step in the chlorophyll biosynthesis pathway. As POR is light
      activated, it allows intermediates in the reaction pathway to be observed by
      initiating catalysis with illumination at low temperatures, a technique that has
      recently been used to study the initial photochemistry. Here, we use low
      temperature spectroscopy to show that the catalytic mechanism of POR involves two
      additional steps, which do not require light and have been termed the "dark"
      reactions. The first of these involves the conversion of the product of the
      initial light-driven reaction, a nonfluorescent radical species, into a new
      intermediate that has an absorbance maximum at 681 nm and a fluorescence peak at
      684 nm. During the second dark step this species gradually blue shifts to yield
      the product, Chlide. The temperature dependence for each of these two processes
      was measured; the data revealed that these steps could only occur close to or
      above the "glass transition" temperature of proteins, suggesting that domain
      movements and/or reorganization of the protein are required for these stages of
      the catalytic mechanism.

PMID- 12525181
TI  - Complex formation between Vibrio harveyi luciferase and monomeric NADPH:FMN
      oxidoreductase.
AB  - A direct transfer of the reduced flavin mononucleotide (FMNH(2)) cofactor of
      Vibrio harveyi NADPH:FMN oxidoreductase (FRP) to luciferase for the coupled
      bioluminescence reaction has been indicated by recent kinetic studies [Lei, B.,
      and Tu, S.-C. (1998) Biochemistry 37, 14623-14629; Jeffers, C., and Tu, S.-C.
      (2001) Biochemistry 40, 1749-1754]. For such a mechanism, a complex formation of
      luciferase with FRP is essential, but until now, no evidence for such a complex
      has been reported. In this work, FRP was labeled at 1:1 molar ratio with the
      fluorophore eosin. The labeled enzyme was about 30% active in either the
      reductase single-enzyme or the luciferase-coupled assay. The labeled FRP in
      either the holo- or apoenzyme form was similar to the native FRP in undergoing a
      monomer-dimer equilibrium. By measuring the steady-state fluorescence anisotropy
      of eosin-labeled FRP, it was shown that luciferase formed a complex at 1:1 molar
      ratio with the monomer of either the apoenzyme or the holoenzyme form of FRP with
      K(d) values of 7 and 11 microM, respectively. Neither the holo- nor the apoenzyme
      of the labeled FRP in the dimeric form was effective in complexing with
      luciferase. At maximal in vivo bioluminescence, the V. harveyi cellular contents
      of luciferase and FRP were estimated to be 172 and 3 microM, respectively. The
      vast majority of FRP would be trapped in the luciferase/FRP complex. Plausible
      physiological significance of such a finding is discussed.

PMID- 12525182
TI  - Glycolipid intermembrane transfer is accelerated by HET-C2, a filamentous fungus
      gene product involved in the cell-cell incompatibility response.
AB  - Among filamentous fungi capable of mycelial growth, het genes play crucial roles
      by regulating heterokaryon formation between different individuals. When fusion
      occurs between fungal mycelia that differ genetically at their het loci, the
      resulting heterokaryotic cells are quickly destroyed. It is unclear how het gene
      products of Podospora anserina trigger heterokaryon incompatibility. One
      unexplored possibility is that glycosphingolipids play a role because the het-c2
      gene encodes a protein that displays 32% sequence identity and an additional 30%
      similarity to the mammalian glycolipid transfer protein. Here, P. anserina
      protoplasts containing wild-type het-c2 genes were shown to have greater
      glycosphingolipid transfer activity than protoplasts with disrupted het-c2 genes,
      a condition previously linked to altered cell compatibility following hyphal
      fusion. The observed glycolipid transfer activity could not be accounted for by
      nonspecific lipid transfer protein activity. Direct assessment showed that
      purified, recombinant HET-C2 accelerates the intermembrane transfer of glycolipid
      in vitro, but that the HET-C2 activity is mitigated much less by negatively
      charged membranes than the mammalian glycolipid transfer protein. The findings
      are discussed within the context of HET-C2 being a member of an emerging family
      of ancestral sphingolipid transfer proteins that play important roles in cell
      proliferation and accelerated death.

PMID- 12525183
TI  - Scanning mutagenesis of the alpha repeats and of the transmembrane acidic
      residues of the human retinal cone Na/Ca-K exchanger.
AB  - The Na/Ca-K exchanger (NCKX) utilizes the inward sodium gradient and outward
      potassium gradient for Ca(2+) extrusion; two distinct NCKX isoforms are expressed
      in the outer segments of retinal rod (NCKX1) and cone (NCKX2) photoreceptors,
      respectively, where NCKX extrudes Ca(2+) that enters photoreceptors via the cGMP
      gated channels. We carried out the first systematic NCKX mutagenesis study in
      which 96 residues were mutated in the human cone NCKX2 cDNA, and functional
      consequences of these mutations were measured; the residues selected for
      mutagenesis are conserved between rod and cone NCKX, the large majority are also
      conserved in NCKX paralogs found in lower organisms, and finally, they include
      the few residues conserved between members of the NCKX and members of the NCX
      (potassium-independent Na/Ca exchange) gene families. Twenty-five residues were
      identified for which mutagenesis reduced NCKX function to <20% of wild-type cone
      NCKX2 activity, while protein expression and plasma membrane targeting were not
      affected. Three classes of residues were found to be most sensitive toward
      mutagenesis: acidic (glutamate/aspartate) residues, polar (serines/threonine)
      residues, and glycine residues. These results are discussed with respect to
      residues that may contribute to the NCKX cation binding site(s).

PMID- 12525184
TI  - High-pressure FTIR study of the stability of horseradish peroxidase. Effect of
      heme substitution, ligand binding, Ca++ removal, and reduction of the disulfide
      bonds.
AB  - The pressure stability of horseradish peroxidase isoenzyme C and the
      identification of possible stabilizing factors are presented. The effect of heme
      substitution, removal of Ca(2+), binding of a small substrate molecule
      (benzohydroxamic acid), and reduction of the disulfide bonds on the pressure
      stability were investigated by FTIR spectroscopy. HRP was found to be extremely
      stable under high pressure with an unfolding midpoint of 12.0 +/- 0.1 kbar. While
      substitution of the heme for metal-free mesoporphyrin did not change the
      unfolding pressure, Ca(2+) removal and substrate binding reduced the midpoint of
      the unfolding by 2.0 and 1.2 kbar, respectively. The apoprotein showed a
      transition as high as 10.4 kbar. However, the amount of folded structure present
      at the atmospheric pressure was considerably lower than that in all the other
      forms of HRP. Reduction of the disulfide bonds led to the least pressure stable
      form, with an unfolding midpoint at 9.5 kbar. This, however, is still well above
      the average pressure stability of proteins. The high-pressure stability and the
      analysis of the pressure-induced spectral changes indicate that the protein has a
      rigid core, which is responsible for the high stability, while there are regions
      with less stability and more conformational mobility.

PMID- 12525185
TI  - Dynamics and entropy of a calmodulin-peptide complex studied by NMR and molecular
      dynamics.
AB  - All-atom, explicit water molecular dynamics simulations of calcium-loaded
      calmodulin complexed with a peptide corresponding to the smooth muscle myosin
      light chain kinase target were carried out at 295 and 346 K. Amide and side chain
      methyl angular generalized order parameters were calculated and analyzed in the
      context of the protein's structure and dynamics. The agreement between amide
      order parameters measured by NMR and those from the simulations was found to be
      good, especially at the higher temperature, indicating both better convergence
      for the latter and excellent transferrability of the CHARMM parameters to the
      higher temperature. Subtle dynamical features such as helix fraying were
      reproduced. A large range of order parameters for the nine calmodulin methionines
      was observed in the NMR, and reproduced quite well in the simulations. The major
      determinant of the methionine order parameter was found to be the proximity to
      side chains of aromatic residues. An upper bound estimate of the difference in
      backbone entropy between loop and helical regions was extracted from the order
      parameters using a model of motion in an effective potential. Although loop
      regions are more flexible than helical regions, it was found that the entropy
      loss per residue upon folding was only approximately 20% less for loops than for
      helices. Pairwise correlated motions, which could significantly lower entropy
      estimates obtained from order parameter analysis alone, were found to be largely
      absent.

PMID- 12525186
TI  - Kinetics of the yeast cystathionine beta-synthase forward and reverse reactions:
      continuous assays and the equilibrium constant for the reaction.
AB  - Cystathionine beta-synthase (CBS) is a pyridoxal-phosphate-dependent enzyme that
      catalyzes a beta-replacement reaction in which the hydroxyl group of serine (L
      Ser) is displaced by the thiol of homocysteine (L-Hcys) to form cystathionine (L
      Cth) in the first step of the trans-sulfuration pathway. A new continuous assay
      for the forward reaction, employing cystathionine beta-lyase and L-lactate
      dehydrogenase as coupling enzymes, is described. It alleviates product inhibition
      by L-Cth and revealed that the values for (1.2 mM) and for substrate inhibition
      by L-Hcys ( = 2.0 mM) are lower than those previously reported. A continuous,
      5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based assay for the CBS-catalyzed
      hydrolysis of L-Cth to L-Ser and L-Hcys provides a tool for investigation of the
      reverse reaction (k(catR) = 0.56 s(-)(1), = 0.083 mM). The (catR)/ versus pH
      profile of ytCBS is bell-shaped with a pH optimum of 8.3, and the pK(a) values
      for the acidic and basic limbs are 8.05 and 8.63, respectively. The latter is
      assigned to the alpha-amino group of L-Cth (pK(a) = 8.54). The internal aldimine
      of ytCBS remains protonated at pH < 11; therefore, the acidic pK(a) is assigned
      to an enzyme functionality that is not associated with the internal aldimine.
      K(eq) was determined directly and from the kinetic parameters, and the values are
      0.61 and 1.2 microM, respectively.

PMID- 12525187
TI  - Potential transition state analogue inhibitors for the penicillin-binding
      proteins.
AB  - Penicillin-binding proteins (PBPs) are ubiquitous bacterial enzymes involved in
      cell wall biosynthesis. The development of new PBP inhibitors is a potentially
      viable strategy for developing new antibacterial agents. Several potential
      transition state analogue inhibitors for the PBPs were synthesized, including
      peptide chloromethyl ketones, trifluoromethyl ketones, aldehydes, and boronic
      acids. These agents were characterized chemically, stereochemically, and as
      inhibitors of a set of low molecular mass PBPs: Escherichia coli (EC) PBP 5,
      Neisseria gonorrhoeae (NG) PBP 3, and NG PBP 4. A peptide boronic acid was the
      most effective PBP inhibitor in the series, with a preference observed for a d
      boroAla-based over an l-boroAla-based inhibitor, as expected given that
      physiological PBP substrates are based on d-Ala at the cleavage site. The lowest
      K(I) of 370 nM was obtained for NG PBP 3 inhibition by Boc-l-Lys(Cbz)-d-boroAla
      (10b). Competitive inhibition was observed for this enzyme-inhibitor pair, as
      expected for an active site-directed inhibitor. For the three PBPs included in
      this study, an inverse correlation was observed between the values for log K(I)
      with 10b and the values for log(k(cat)/K(m)) for activity against the analogous
      substrate, and K(m)/K(I) ratios were 90, 1900, and 9600 for NG PBP 4, EC PBP 5,
      and NG PBP 3, respectively. These results demonstrate that peptide boronic acids
      can be effective transition state analogue inhibitors for the PBPs and provide a
      basis for the use of these agents as probes of PBP structure, function, and
      mechanism, as well as a possible basis for the development of new PBP-targeted
      antibacterial agents.

PMID- 12525188
TI  - Interaction of human telomerase with its primer substrate.
AB  - Telomerase is a ribonucleoprotein responsible for maintaining the ends of linear
      chromosomes in nearly all eukaryotic cells. In humans, expression of the enzyme
      is limited primarily to the germ line and progenitor cell populations. In the
      absence of telomerase activity, telomeres shorten with each cell division until a
      critical length is reached, which can result in the cessation of cell division.
      The enzyme is required for cell immortality, and its activity has been detected
      in the vast majority of human tumors. Because of this, telomerase is an
      attractive target for inhibition in anticancer therapy. To learn more about the
      biochemistry of the human enzyme and its substrate recognition, we have examined
      the binding properties of single-stranded oligonucleotide primers that serve as
      telomerase substrates in vitro. We have used highly purified human enzyme and
      employed a two-primer method for determining the dissociation rates of these
      primers. Primers having sequence permutations of (TTAGGG)(3) were found to have
      considerably different affinities. They had t(1/2) values that ranged from 14 min
      to greater than 1200 min at room temperature. A primer ending in the GGG register
      formed the most stable complex with the enzyme. This particular register imparted
      stability to a nontelomeric primer resulting in a nearly 100-fold decrease in the
      k(off). We have found that interactions of telomerase with primer substrates are
      stabilized mainly by contacts with the protein subunit of the enzyme (hTERT).
      Base-pairing between the primer and the template region of telomerase contributes
      minimally to its stabilization.

PMID- 12525189
TI  - The training of head and neck surgeons: the care of head and neck patients: 2002
      Presidential Address, American Head and Neck Society.

PMID- 12525190
TI  - Neck dissection: an operation in evolution: Hayes Martin lecture.

PMID- 12525191
TI  - Therapeutic decision making in stages III and IV head and neck squamous cell
      carcinoma.
AB  - BACKGROUND: The best treatment for advanced head and neck cancer remains unclear.
      Proponents of various therapeutic regimens continue to debate this issue with
      inconclusive and frequently biased data and with carefully selected patients in
      controlled trials to support their approach. To assess the outcome of patients in
      a real-world situation, we reviewed a prospectively maintained database of
      patients with head and neck cancer. METHODS: We reviewed data from 591
      consecutive patients with stage III or IV squamous cell carcinoma treated at a
      university medical center from January 1, 1992, through December 31, 2000, and
      analyzed survival using the Kaplan-Meier method. RESULTS: Overall survival was
      48%, 40%, and 33% at 2, 3, and 5 years, respectively. We found a significant
      death rate due to comorbid conditions. The primary tumor was treated surgically
      (with or without postoperative radiation) in 363 patients, with survival of 55%,
      46%, and 38% at 2, 3, and 5 years, respectively. The tumor was treated primarily
      with radiation therapy (with or without neck dissection) in 193 patients, with
      survival of 40%, 33%, and 27% at 2, 3, and 5 years, respectively. Overall
      survival in the surgical group was better than in the radiation group (P =.005,
      log-rank chi 2 test). The radiation group was subcategorized into those who
      underwent radiation because the tumor was so advanced as to be unresectable (n =
      86), because they were too unhealthy to undergo radical surgery (n = 23), and
      because they elected radiation therapy (n = 84). Survival in each of the
      radiation subgroups at 2, 3, and 5 years was 28%, 20%, and 14%, respectively, in
      the unresectable group; 34%, 22%, and 11%, respectively, in the unhealthy group;
      and 57%, 53%, and 46%, respectively, in the elective group. Thus, survival in the
      elective radiation subgroup exceeded that of the surgical group, although not
      statistically. We analyzed data regarding T and N stages, age, race, surgical
      margin status, postoperative radiation therapy, chemotherapy, radiation dose, and
      tumor site. Multivariate analysis of the surgical group and elective radiation
      subgroup showed that N stage and age were the strongest predictors of survival
      and that the method of therapy was not significant. For oropharyngeal cancer, the
      patients in the elective radiation subgroup did as well as the surgical group.
      Many patients were noncompliant with portions of therapy, with a resulting
      reduction in survival. CONCLUSIONS: The data demonstrate the value of analyzing a
      consecutive series of patients with advanced head and neck cancer. By including
      patients with comorbidities and those who are noncompliant, we determined a
      realistic expectation of patient outcomes. By including all patients, the data
      dramatically show the impact of age, comorbidity, and advanced stage on survival.
      The survival of patients who underwent elective radiation therapy in combination
      with neck dissection was similar to that of patients treated with primary tumor
      surgery. This was particularly true for oropharyngeal tumors. The site and stage
      specific data are useful in counseling patients with advanced head and neck
      cancer regarding treatment choices.

PMID- 12525192
TI  - Transoral laser microsurgery for squamous cell carcinoma of the base of the
      tongue.
AB  - OBJECTIVE: To determine the role of transoral laser microsurgery for base of
      tongue squamous cell carcinoma. DESIGN: Retrospective unicenter study of the
      oncologic and functional results of laser microsurgery of tongue base carcinoma
      performed between 1986 and 1997. SETTINGS: University hospital department.
      PATIENTS: We reviewed 48 previously untreated patients with base of tongue
      squamous cell carcinoma, who were treated with transoral laser microsurgery.
      Distribution of the T categories were T1, 2%; T2, 25%; T3, 15%; and T4, 58%; 94%
      belonged to the stages III and IVa. Selective neck dissection was performed in 43
      patients; 23 patients underwent postoperative radiotherapy with or without
      simultaneous chemotherapy. MAIN OUTCOME MEASURES: Local control rate, recurrence
      free and overall survival rates, mean performance status scale scores for
      normalcy of diet and understandability of speech. RESULTS: The Kaplan-Meier 5
      year local control rate was 85%. There was no local recurrence in T1 and T2
      lesions, but there was a 20% local recurrence rate in T3 and T4 tumors. Kaplan
      Meier 5-year recurrence-free and overall survival rates were 73% and 52%,
      respectively. Mean performance status scale scores were 92% for normalcy of diet
      and 88% for understandability of speech. Twenty-one patients survived at least 5
      years after treatment. They have a preserved larynx and live without tracheostoma
      or gastrostomy tube. CONCLUSIONS: Our concept of organ and function preserving
      laser microsurgery for selected patients with base of tongue cancer seems to be
      justified considering the achieved oncological and functional results. Final
      proof of the effectiveness of the new therapeutic concept presented herein
      requires well-designed prospective studies.

PMID- 12525193
TI  - Outcome of salvage total laryngectomy following organ preservation therapy: the
      Radiation Therapy Oncology Group trial 91-11.
AB  - OBJECTIVE: To evaluate the incidence of morbidity, mortality, and disease control
      for patients requiring salvage total laryngectomy (TL) following organ
      preservation therapy. DESIGN: Patients entered into a 3-arm randomized
      prospective multi-institutional trial for laryngeal preservation who required TL
      following initial treatment. SETTING: The Radiation Therapy Oncology Group 91-11
      trial for laryngeal preservation. PATIENTS: From 1992 to 2000, 517 evaluable
      patients were randomized to receive chemotherapy followed by radiation therapy
      (arm 1), concomitant chemotherapy and radiation therapy (arm 2), or radiation
      therapy alone (arm 3). RESULTS: Overall, TL was required in 129 patients. The
      incidence was 28%, 16%, and 31% in arms 1, 2, and 3, respectively (P =.002). Of
      these, 7 patients (5%) required TL for aspiration or necrosis. Following TL, the
      incidence of major and minor complications ranged from 52% to 59% and did not
      differ significantly among the 3 arms. Pharyngocutaneous fistula was lowest in
      arm 3 (15%) and highest in arm 2 (30%) (P>.05). There was 1 perioperative death.
      Local-regional control following salvage TL was 74% for arms 1 and 2 and 90% for
      arm 3. At 24 months, the overall survival was 69% (arm 1), 71% (arm 2), and 76%
      (arm 3) (P>.73). CONCLUSIONS: Laryngectomy following organ preservation treatment
      is associated with acceptable morbidity. Perioperative mortality is low but up to
      one third of patients will develop a pharyngocutaneous fistula. Local-regional
      control is excellent for this group of patients. Survival following salvage TL
      was not influenced by the initial organ preservation treatment.

PMID- 12525194
TI  - Medical malpractice and facial nerve paralysis.
AB  - BACKGROUND: Iatrogenic facial nerve paralysis is a devastating surgical
      complication that occasionally results in litigation. OBJECTIVE: To analyze
      litigation trends to better understand the causes and outcomes of suits involving
      facial nerve paralysis to prevent future litigation and improve physician
      education. DESIGN: Retrospective review. SETTING: All US civil trials.
      PARTICIPANTS: All state and federal civil trials alleging malpractice and facial
      nerve paralysis were reviewed. METHODS: Jury verdict reviews from January 1,
      1985, to December 31, 2000, were obtained from a computerized legal database and
      analyzed. Reviews compile data on defendants, plaintiffs, allegations of wrong
      doing, and expert witness specialties, and provide case summaries. Fifty-three
      cases from 19 of the 50 states were obtained. Data were entered into a
      spreadsheet for analysis. MAIN OUTCOME MEASURES: Verdicts and indemnity payments.
      RESULTS: Suits reviewed were as follows: cosmetic, 12 (23%); otologic, 13 (25%);
      nonneoplastic disease of the parotid or other benign conditions of the head and
      neck, 15 (28%); benign neoplasms of the parotid, 9 (17%); malignant neoplasms of
      the parotid, 1 (2%); and temporomandibular joint operations, 3 (6%) (percentages
      do not total 100 because of rounding). Allegations of negligence were frequently
      multiple and included lack of informed consent (16 [30%] of 53), failure to
      diagnose (10 [19%] of 53), and surgical misadventures (47 [89%] of 53). Excluding
      failure to obtain consent or to diagnose, 28 suits still alleged negligence based
      solely on a surgical misadventure. Of these suits, 12 (63%) resulted in plaintiff
      awards. CONCLUSIONS: Surgeons must emphasize and document the likelihood and
      consequences of this devastating complication to all patients undergoing surgery
      in this area. Risk management goals include a thorough and timely examination and
      careful and thoughtful surgical approaches. However, patient rapport and bedside
      manner may be the only protection the surgeon has from litigation arising from
      this complication.

PMID- 12525195
TI  - Regional tumor recurrence after supraomohyoid neck dissection.
AB  - OBJECTIVE: To evaluate the recurrence of lymphatic metastases in patients with
      squamous cell carcinoma of the oral cavity treated with supraomohyoid neck
      dissection with and without postoperative radiotherapy. DESIGN: A nonrandomized
      retrospective study. SETTING: Department of Otolaryngology and Head and Neck,
      State University of Campinas, Sao Paulo, Brazil, a tertiary referral center.
      PATIENTS: Thirty-two patients with squamous cell carcinoma of the oral cavity
      without previous treatment and a minimum follow-up period of 2 years were
      studied. There were 36 supraomohyoid neck dissections, of which 31 were elective
      (clinically negative nodes) and 5 therapeutic (clinically positive nodes).
      INTERVENTION: Resection of the primary tumor and supraomohyoid neck dissection,
      with or without postoperative radiotherapy. MAIN OUTCOME MEASURES: Evaluation of
      neck tumor recurrence according to clinical and histopathological findings in the
      neck and use of postoperative radiotherapy. RESULTS: The overall recurrence rate
      was 6% (2 patients). Recurrences were seen in 1 clinically negative neck (3%) and
      1 clinically positive neck (20%). The presence of clinically or
      histopathologically positive nodes, number of positive nodes, and use of adjuvant
      radiotherapy did not influence the rate of neck tumor recurrence with a
      statistically significant difference. CONCLUSIONS: Neck tumor recurrence in
      procedures with clinically positive nodes was 6.3 times greater than in those
      with clinically negative nodes. There was no difference in regional recurrence of
      histopathologically positive node necks with or without the addition of
      postoperative radiotherapy. Neck tumor recurrence was not statistically
      influenced by clinically and histopathologically positive nodes, multiple
      positive nodes, and use of postoperative radiotherapy.

PMID- 12525196
TI  - Reliability of sentinel lymph node mapping with biopsy for head and neck
      cutaneous melanoma.
AB  - OBJECTIVES: To determine (1) the reliability of sentinel lymph node mapping with
      biopsy (SLNB) in head and neck cutaneous melanoma to accurately stage nodal
      basins and (2) the safety of SLNB in both the neck and parotid regions. DESIGN:
      Retrospective cohort study with a median follow-up of 25 months. All patients had
      a minimum follow-up of 1 year. SETTING: Academic medical center. PATIENTS: Eighty
      evaluable patients diagnosed as having head and neck cutaneous melanoma and
      staged using SLNB. INTERVENTIONS: Sentinel lymph nodes were identified using
      preoperative lymphoscintigraphy and a combination of intraoperative gamma probe
      and isosulfan blue dye. Patients with a SLN positive for melanoma underwent
      therapeutic lymphadenectomy followed by an evaluation for adjuvant therapies.
      Patients with a negative SLNB result were followed up clinically. MAIN OUTCOME
      MEASURES: Percentage of positive SLNs, regional recurrence in the setting of a
      negative SLNB result (false-negative rate), and procedure complications. RESULTS:
      The mean Breslow depth was 2.35 mm. A SLN was identified in 77 (96.3%) of cases,
      with an average of 2.18 nodes per patient. Of the sentinel nodes identified, 74%
      were from the neck region. The remaining 26% were from the parotid basin. No
      facial nerve complications occurred. Of the patients, 14 (18%) were SLN positive
      for metastatic melanoma. The regional failure rate in the setting of a negative
      SLNB result was 4.5%. CONCLUSIONS: Sentinel lymph node mapping with biopsy is a
      reliable technique to diagnose regional spread from head and neck cutaneous
      melanoma. This procedure can be performed in both neck and parotid nodal basins
      with safety and accuracy similar to non-head and neck sites.

PMID- 12525197
TI  - Partial laryngectomy with imbrication laryngoplasty for glottic carcinoma.
AB  - BACKGROUND: Treatment options for unilateral glottic carcinoma include radiation
      therapy, partial laryngectomy, and endoscopic cordectomy. We used partial
      laryngectomy with imbrication laryngoplasty (PLIL) for definitive treatment with
      curative intent in a select group of patients. STUDY DESIGN: Retrospective
      multicenter review of 24 patients treated with PLIL. Data collection included
      demographics, tumor characteristics, time to decannulation, time to oral food
      intake, local control, survival, voice result as judged by the physician, voice
      result as judged by the patient, and patient satisfaction. SETTING: Five academic
      medical centers. METHODS: PLIL includes a composite resection of the entire vocal
      fold, with its ligament, muscle, adjacent paraglottic tissues, and the adjacent
      block of thyroid cartilage. A neocord is reconstructed by imbricating the
      remaining thyroid cartilage strips and covering them with a false vocal fold
      flap. RESULTS: A total of 24 patients (T1, n = 13; T2, n = 10; and T3, n = 1)
      underwent PLIL. Median time to decannulation was 4 days, and median time to oral
      food intake was 5 days. Clear margins were achieved in 23 patients (96%). Follow
      up ranged from 1 to 11 years (median duration of follow-up, 5.5 years). In the
      patients who had clear margins at the initial surgery, the rate of overall
      disease control was 100%. Voice quality was judged by the physician as good or
      excellent in 100% of the patients who underwent PLIL, and as better than typical
      hemilaryngectomy in 23 patients (96%). Twenty-three patients (96%) were satisfied
      with their voice quality. CONCLUSIONS: PLIL provides us with a single modality
      curative approach to unilateral glottic carcinoma. It also provides rapid
      recovery of oral and/or nasal airway and swallowing, excellent voice quality, and
      a disease-control rate similar to or better than other treatment modalities.

PMID- 12525198
TI  - Influence of prior hyperbaric oxygen therapy in complications following
      microvascular reconstruction for advanced osteoradionecrosis.
AB  - OBJECTIVE: To review surgical outcomes in the management of advanced mandibular
      osteoradionecrosis (ORN) with aggressive debridement and microvascular
      reconstruction. DESIGN: Retrospective cohort study. SETTING: Tertiary care
      referral center. PATIENTS: Thirty patients with Marx stage III ORN of the
      mandible who underwent debridement with microvascular reconstruction. Two types
      of patients with stage III disease were included: those who had not received
      prior hyperbaric oxygen (HBO) therapy but who presented with a pathologic
      fracture, orocutaneous fistula, or bony resorption of the inferior border of the
      mandible (group 1, n = 9), and those who were classified as having stage III
      disease as a result of failure of previous debridement and HBO therapy (group 2,
      n = 21). MAIN OUTCOME MEASURE: Clinical resolution of ORN as well as surgical
      perioperative complications. INTERVENTIONS: Debridement and primary free flap
      reconstruction in all patients; Perioperative HBO therapy in 3 patients. RESULTS:
      The overall complication rate was 43%, but 29 (97%) of 30 patients had clinical
      resolution of their ORN. There were no flap failures. After smoking status and
      use of perioperative HBO were adjusted for, patients with Marx stage III disease
      who had received prior HBO therapy (group 2) were significantly more likely to
      have postoperative wound infection (P =.01) and overall surgical complications (P
      =.04) than were patients with stage III disease who had never been treated with
      HBO (group 1). Perioperative HBO therapy was provided too infrequently to comment
      on its effectiveness. CONCLUSIONS: Microvascular reconstruction is effective in
      the treatment of patients with mandibular ORN. Management of mandibular ORN can
      be successfully achieved without the use of perioperative HBO therapy. Because
      only 3 patients received perioperative HBO therapy, we are unable to comment on
      its potential benefit. Patients in whom prior HBO therapy has failed are
      significantly more likely to have surgical complications than are other patients
      with Marx stage III disease, and further study is required to improve outcomes in
      this subgroup of patients.

PMID- 12525199
TI  - Surgical anatomy of the extralaryngeal aspect of the superior laryngeal nerve.
AB  - OBJECTIVES: To describe the topography of the superior laryngeal nerve (SLN) and
      to evaluate the influence of gender, ethnicity, side of the neck, and individual
      height on the topography of the SLN. DESIGN: Anatomical study of human cadavers.
      SUBJECTS: Fifty fresh human cadavers (19 female subjects and 31 male subjects;
      age range, 22-89 years; mean age, 61 years) were randomly selected for this
      study. The subjects were divided into nonwhite (n = 18) and white (n = 32) ethnic
      groups. The t test and linear regression were used for statistical analysis of
      data. RESULTS: All SLNs emerged medially to the vagus nerve. The SLNs mostly
      divided into internal (ibSLN) and external (ebSLN) branches distally from their
      origin (94%). The mean +/- SE length of the SLN trunk was 16.7 +/- 0.9 mm and was
      affected by gender (P =.01) but not ethnicity (P =.57), side of the neck (P
      =.96), or individual height (R2 = 0.01; P =.33). The length of the ibSLN reached
      44.9 +/- 1.0 mm and was unaffected by gender (P =.91), ethnicity (P =.24), side
      (P =.40), or height (R2<0.01; P =.71). The length of the ebSLN measured 62.6 +/-
      1.2 mm and was unaffected by gender (P =.69), ethnicity (P =.42), side (P =.26),
      or height (R2<0.01; P =.85). The mean +/- SE angle between the ibSLN and the
      tracheoesophageal sulcus was 49 degrees +/- 1 degrees and was unaffected by
      gender (P =.35), ethnicity (P =.11), side (P =.26), or height (R2<0.01; P =.96).
      Only 1 subject demonstrated a bilateral anatomical variation of the ibSLN close
      to its entrance into the thyrohyoid membrane. CONCLUSIONS: The topography of the
      SLN has a few anatomical variations and is unaffected by gender, ethnicity, side
      of the neck, and individual height, except that the SLN is longer in males than
      in females. These findings are important in that they can help in the prevention
      of SLN injuries during operations such as laryngectomy and neck dissection, as
      well as in the planning of laryngeal reinnervation and transplantation.

PMID- 12525200
TI  - Elective management of the clinically negative neck by otolaryngologists in
      patients with oral tongue cancer.
AB  - BACKGROUND: The treatment of patients with squamous cell carcinoma of the head
      and neck who have a clinically negative (cN0) neck remains controversial.
      Furthermore, the treatment delivered to patients with a cN0 neck by practicing
      otolaryngologists is not known. OBJECTIVE: To determine the variability in the
      management of the cN0 neck in the otolaryngology community. DESIGN, SETTING, AND
      PARTICIPANTS: A random survey of 763 board-certified otolaryngologists in the
      United States. MAIN OUTCOME MEASURES: Physician respondents' preferences for
      observation vs treatment of the cN0 neck and the treatment modalities chosen.
      RESULTS: Forty-one percent of the surveyed physicians responded. Nearly 10% of
      the respondents observed all patients with a cN0 neck. Otolaryngologists who
      treat 35 or more new patients with cancer each year were more likely to perform
      elective treatment of the neck for a T2 lesion of the oral tongue than those who
      treat 10 or fewer patients each year (P =.03). They were also more likely to
      treat patients with a cN0 neck when the risk of occult cervical metastases was
      greater than 15% to 20% (P =.04). A comprehensive neck dissection was the
      preferred lymphadenectomy procedure for 21% of the otolaryngologists surveyed.
      CONCLUSIONS: Variations in the treatment of the cN0 neck are associated with
      differences in the frequency of treatment of patients with head and neck cancer
      by otolaryngologists. Uniformity of care must be established within the
      otolaryngology community by developing widely accepted evidence-based guidelines
      and referring patients to surgeons who routinely treat head and neck cancer.

PMID- 12525201
TI  - A critical evaluation of critical pathways in head and neck cancer.
AB  - BACKGROUND: Critical pathways have been purported to decrease resource
      utilization in the management of head and neck cancer. Prior reports have
      documented shorter lengths of stay (LOS) for pathway patients than for historical
      cohorts. OBJECTIVE: To critically evaluate the impact of critical pathways on LOS
      after laryngectomy. DESIGN: Length-of-stay trends of 2 concurrent observational
      cohorts of laryngectomy patients (September 1992 to February 1999) were compared,
      1 at each of 2 medical centers. One center instituted a critical pathway for
      laryngectomy patients in February 1997; the other never used such pathways. In
      addition, we examined the independent impact of the critical pathway at the
      pathway institution after controlling for date of laryngectomy (which reflected
      temporal trends) and other confounding variables. RESULTS: Both centers
      experienced reductions in LOS after February 1997, but there was no statistically
      significant difference between the reductions (1.9 days at the pathway center vs
      1.5 days at the nonpathway center; P>.05). Multivariable linear and linear spline
      regression models demonstrated that the use of critical pathways at the pathway
      institution had no statistically significant impact on LOS after controlling for
      the date of laryngectomy. CONCLUSIONS: Pathway implementation has a limited
      direct impact on LOS in relatively low-volume procedures such as laryngectomy.
      Although pathways may influence utilization trends, their impact is likely
      mediated by the development and educational process that accompanies pathway
      adoption rather than implementation of the pathway itself. The inclusion of
      temporal trends and contemporary cohorts provides substantial insight into the
      effectiveness of critical pathways.

PMID- 12525202
TI  - Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of
      anaplastic transformation by means of the inter-simple sequence repeat polymerase
      chain reaction.
AB  - BACKGROUND: In thyroid tumors, the coexistence of well- and poorly differentiated
      tumor types has led to the hypothesis that poorly differentiated thyroid tumors
      develop from well-differentiated thyroid tumors. By evaluating the genomic
      instability of histologically distinct but coexisting tumor foci, this study
      aimed to develop an improved understanding of thyroid tumorigenesis and tumor
      evolution. DESIGN: Laser capture microdissection (LCM) was carried out on
      archival formalin-fixed, paraffin-embedded sections from a tumor containing foci
      of classic papillary thyroid cancer and anaplastic thyroid cancer. DNA was
      extracted from each microdissected tumor focus. In addition, cryopreserved bulk
      normal and neoplastic thyroid tissue underwent DNA extraction. All DNA samples
      were subsequently evaluated for genomic instability by means of inter-simple
      sequence repeat polymerase chain reaction. RESULTS: The LCM DNA from each
      archival paraffin-embedded tumor focus demonstrated unique patterns of banding as
      compared with the cryopreserved tumor and normal tissue DNA. Thus, intratumoral
      variability in genomic instability was observed. Comparison of inter-simple
      sequence repeat polymerase chain reaction patterns of LCM DNA from adjacent foci
      of papillary and anaplastic tumors showed conserved genome alterations.
      CONCLUSIONS: At the genome level, thyroid tumors may be highly heterogeneous. The
      intratumoral histologic heterogeneity observed in thyroid neoplasms reflects
      genetically heterogeneous underlying tumor cell populations that are demonstrated
      by the observed differences in their rates and extents of genomic instability.
      The conserved genomic alterations in the microdissected papillary and anaplastic
      foci suggest intratumoral evolution, with transformation of a preexisting
      papillary tumor to anaplastic carcinoma.

PMID- 12525203
TI  - Connective tissue disease coincident with nasopharyngeal carcinoma: two sporadic
      cases in a Western population.
AB  - OBJECTIVES: To increase awareness of the potential coexistence of connective
      tissue disease and nasopharyngeal carcinoma in a Western population, to consider
      possible causes for this phenomenon, and to provide recommendations for clinical
      management. DESIGN: Case report. SETTING: Academic tertiary referral practice.
      PATIENTS: Ninety-four patients with nasopharyngeal carcinoma were initially
      treated, and 20 were followed for 10 years. Of these, 2 were diagnosed as having
      coexistent connective tissue disease. MAIN OUTCOME MEASURE: The clinical course
      of coexisting diseases. RESULTS: Most previous reports of the coexistence of
      nasopharyngeal carcinoma and connective tissue disease involve southern Chinese
      populations. There are distinct similarities between those series and the cases
      presented herein. The association can take several forms with differing order of
      presentation and spectrum of symptoms. A variety of mechanisms have been proposed
      for the dual development of the 2 disease states. CONCLUSIONS: Connective tissue
      disease and nasopharyngeal carcinoma may coexist in white patients in a manner
      similar to that seen in Asian populations. Awareness of this possibility is an
      indication for special screening measures.

PMID- 12525205
TI  - DentaScan as an accurate method of predicting mandibular invasion in patients
      with squamous cell carcinoma of the oral cavity.
AB  - OBJECTIVE: To determine the diagnostic accuracy of a dental computed tomographic
      software program, DentaScan, in assessing mandibular bone invasion in patients
      with squamous cell carcinoma (SCC) of the oral cavity clinically fixed to the
      mandible. DESIGN: Retrospective chart review. SETTING: Academic tertiary care
      medical center. PATIENTS: Thirty-six consecutive patients underwent DentaScan
      imaging of the mandible prior to composite resection for tumor ablation. All
      patients included in this review had SCC of the oral cavity clinically fixed to
      the mandible. A final histopathology report specifically addressing the presence
      or absence of bone invasion was available for each patient. RESULTS: The
      diagnostic accuracy for DentaScan in this study was as follows: sensitivity, 95%;
      specificity, 79%; positive predictive value, 87%; and negative predictive value,
      92%. CONCLUSION: DentaScan is an accurate method of preoperative evaluation for
      mandibular invasion in patients with SCC of the oral cavity.

PMID- 12525204
TI  - High incidence of head and neck squamous cell carcinoma in patients with Fanconi
      anemia.
AB  - BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive disorder
      characterized by a high degree of genomic instability and predisposition to
      cancer development. Recent evidence suggests that the incidence of head and neck
      squamous cell carcinoma (HNSCC) may be increased in patients with FA. OBJECTIVE:
      To determine the cumulative incidence, tumor distribution, and outcome of HNSCC
      in patients with FA. DESIGN AND SETTING: We analyzed data from 754 subjects from
      the International Fanconi Anemia Registry, a prospectively collected database of
      patients with FA. MAIN OUTCOME MEASURES: Cumulative incidence of HNSCC and 2-year
      overall, relapse-free and disease-specific survival. RESULTS: Of the 754 patients
      in the International Fanconi Anemia Registry, 19 (3%) had HNSCC. This is a
      significantly higher incidence of HNSCC compared with that observed in the
      general population (standardized incidence ratio, 500; 95% confidence interval,
      300-781) (P<.001). The patients' age ranged from 15 to 49 years (median, 31
      years), and there was a 2:1 female predominance. Surgical treatment was well
      tolerated (n = 17); however, radiation therapy and chemotherapy were associated
      with significant morbidity and mortality. Of the 19 patients, 10 (53%) developed
      locoregional recurrences within a median of 16 months from diagnosis. The median
      follow-up was 29 months. The 2-year disease-specific, overall, and relapse-free
      survival rates were 49%, 49%, and 42%, respectively. The cumulative incidence of
      relapse by the age of 40 years was 50%. CONCLUSIONS: In patients with FA, there
      is a high incidence of aggressive HNSCC at a young age. Surgery remains the
      mainstay of treatment because patients with FA tolerate radiation therapy and
      chemotherapy poorly, with significant morbidity. An increased understanding of FA
      associated malignancies is not only important in the clinical management of
      patients with FA but can also elucidate the role of chromosomal instability in
      the development of HNSCC in general.

PMID- 12525206
TI  - Orthotopic tracheal allografts undergo reepithelialization with recipient-derived
      epithelium.
AB  - BACKGROUND: While the rejection of heterotopic tracheal allografts is
      characterized by complete airway obliteration, the rejection of orthotopic
      allografts leads to airway edema and cellular infiltrate of the lamina propria,
      but is not associated with obliteration. We hypothesized that orthotopic tracheal
      allografts undergo reepithelialization with recipient-derived mucosa and that
      this process prevents airway obliteration. METHODS: Thirty mice were randomly
      assigned to 6 experimental groups. BALB/c donor tracheal segments were
      transplanted orthotopically or heterotopically into syngeneic BALB/c or major
      histocompatability mismatched allogeneic C57BL/6 recipients. Recipients of
      allogeneic grafts were divided into a nonimmunosuppression group and an
      immunosuppression group (cyclosporine, 7 mg/kg per day). Twenty-one days after
      transplantation, histological assessment, immunohistochemistry for CD4 and CD8
      lymphocyte infiltration and major histocompatibility-specific
      immunohistochemistry were performed on the grafts to assess rejection and donor
      or recipient origin of tissue. RESULTS: Untreated heterotopic allografts
      underwent complete airway obliteration by day 21. This response was prevented
      with cyclosporine immunosuppression. Untreated orthotopic allografts, however,
      demonstrated edema and lymphocytic infiltrate of the lamina propria resulting in
      clinical stridor without airway obliteration. Immunosuppressed orthotopic
      allografts did not develop edema or infiltrate of the lamina propria and
      consequently stridor did not occur. Immunohistochemical analysis demonstrated
      migration of recipient-derived mucosa into the donor allograft segment in both
      the untreated and treated orthotopic groups. CONCLUSIONS: Airway obliteration
      characteristic of rejecting heterotopic tracheal allografts does not occur in the
      orthotopic allografts. Migration of recipient mucosa into the donor allograft
      appears to prevent airway obliteration in the orthotopic allografts. These
      findings suggest that the orthotopic tracheal transplantation model more
      accurately represents the biological behavior of clinical tracheal allografts
      than the traditional heterotopic model.

PMID- 12525207
TI  - Fungal infection of the epiglottis simulating a clinical malignancy.
AB  - Primary fungal infection of the larynx is rare. We present a case of primary
      laryngeal invasive fungal infection in a patient with Felty syndrome. The lesion
      in the epiglottis resembled a malignant process and the whole epiglottis was
      excised endoscopically. No neoplasia was found and the cultures of the epiglottis
      grew Candida glabrata. We propose that the diagnosis of laryngeal candidiasis be
      considered in adult patients with certain predisposing factors, eg,
      immunodeficiency syndromes, but the possibility of underlying malignancy must be
      ruled out.

PMID- 12525208
TI  - Pathology quiz case. Granular cell tumor of the tongue, with extensive overlying
      pseudoepitheliomatous hyperplasia.

PMID- 12525209
TI  - Radiology quiz case 1. Fibromyxoid tumor of the petrous apex.

PMID- 12525210
TI  - Radiology: radiology quiz case 2. Atypical lipomatous tumor, a variant of well
      differentiated liposarcoma.

PMID- 12525211
TI  - A piece of my mind. Convictions.

PMID- 12525212
TI  - PEP talk: treating nonoccupational HIV exposure.

PMID- 12525213
TI  - Imaging to diagnose cardiovascular disease.

PMID- 12525220
TI  - Challenges facing family practice and primary care.

PMID- 12525221
TI  - Challenges facing family practice and primary care.

PMID- 12525222
TI  - Challenges facing family practice and primary care.

PMID- 12525223
TI  - Challenges facing family practice and primary care.

PMID- 12525224
TI  - Challenges facing family practice and primary care.

PMID- 12525225
TI  - Challenges facing family practice and primary care.

PMID- 12525227
TI  - Safety of urinary catheters.

PMID- 12525230
TI  - Humming, nitric oxide, and paranasal sinus obstruction.

PMID- 12525231
TI  - Change in the quality of care delivered to Medicare beneficiaries, 1998-1999 to
      2000-2001.
AB  - CONTEXT: Despite widespread concern regarding the quality and safety of health
      care, and a Medicare Quality Improvement Organization (QIO) program intended to
      improve that care in the United States, there is only limited information on
      whether quality is improving. OBJECTIVE: To track national and state-level
      changes in performance on 22 quality indicators for care of Medicare
      beneficiaries. DESIGN, PATIENTS, AND SETTING: National observational cross
      sectional studies of national and state-level fee-for-service data for Medicare
      beneficiaries during 1998-1999 (baseline) and 2000-2001 (follow-up). MAIN OUTCOME
      MEASURES: Twenty-two QIO quality indicators abstracted from state-wide random
      samples of medical records for inpatient fee-for-service care and from Medicare
      beneficiary surveys or Medicare claims for outpatient care. Absolute improvement
      is defined as the change in performance from baseline to follow-up (measured in
      percentage points for all indicators except those measured in minutes); relative
      improvement is defined as the absolute improvement divided by the difference
      between the baseline performance and perfect performance (100%). RESULTS: The
      median state's performance improved from baseline to follow-up on 20 of the 22
      indicators. In the median state, the percentage of patients receiving appropriate
      care on the median indicator increased from 69.5% to 73.4%, a 12.8% relative
      improvement. The average relative improvement was 19.9% for outpatient indicators
      combined and 11.9% for inpatient indicators combined (P<.001). For all but one
      indicator, absolute improvement was greater in states in which performance was
      low at baseline than those in which it was high at baseline (median r = -0.43;
      range: 0.12 to -0.93). When states were ranked on each indicator, the state's
      average rank was highly stable over time (r = 0.93 for 1998-1999 vs 2000-2001).
      CONCLUSIONS: Care for Medicare fee-for-service plan beneficiaries improved
      substantially between 1998-1999 and 2000-2001, but a much larger opportunity
      remains for further improvement. Relative rankings among states changed little.
      The improved care is consistent with QIO activities over this period, but these
      cross-sectional data do not provide conclusive information about the degree to
      which the improvement can be attributed to the QIOs' quality improvement efforts.

PMID- 12525232
TI  - Lung cancer screening with helical computed tomography in older adult smokers: a
      decision and cost-effectiveness analysis.
AB  - CONTEXT: Encouraged by direct-to-consumer marketing, smokers and their physicians
      are contemplating lung cancer screening with a promising but unproven imaging
      procedure, helical computed tomography (CT). OBJECTIVE: To estimate the potential
      benefits, harms, and cost-effectiveness of lung cancer screening with helical CT
      in various efficacy scenarios. DESIGN, SETTING, AND POPULATION: Using a computer
      simulated model, we compared annual helical CT screening to no screening for
      hypothetical cohorts of 100 000 current, quitting, and former heavy smokers, aged
      60 years, of whom 55% were men. We simulated efficacy by changing the clinical
      stage distribution of lung cancers so that the screened group would have fewer
      advanced-stage cancers and more localized-stage cancers than the nonscreened
      group (ie, a stage shift). Our model incorporated known biases in screening
      programs such as lead time, length, and overdiagnosis bias. MAIN OUTCOME
      MEASURES: We measured the benefits of screening by comparing the absolute and
      relative difference in lung cancer-specific deaths. We measured harms by the
      number of false-positive invasive tests or surgeries per 100 000 and incremental
      cost-effectiveness in US dollars per quality-adjusted life-year (QALY) gained.
      RESULTS: Over a 20-year period, assuming a 50% stage shift, the current heavy
      smoker cohort had 553 fewer lung cancer deaths (13% lung cancer-specific
      mortality reduction) and 1186 false-positive invasive procedures per 100 000
      persons. The incremental cost-effectiveness for current smokers was $116 300 per
      QALY gained. For quitting and former smokers, the incremental cost-effectiveness
      was $558 600 and $2 322 700 per QALY gained, respectively. Other than the degree
      of stage shift, the most influential parameters were adherence to screening,
      degree of length or overdiagnosis bias in the first year of screening, quality of
      life of persons with screen-detected localized lung cancers, cost of helical CT,
      and anxiety about indeterminate nodule diagnoses. In 1-way sensitivity analyses,
      none of these parameters was sufficient to make screening highly cost-effective
      for any of the cohorts. In multiway sensitivity analyses, a program screening
      current smokers was $42 500 per QALY gained if extremely favorable estimates were
      used for all of the influential parameters simultaneously. CONCLUSION: Even if
      efficacy is eventually proven, screening must overcome multiple additional
      barriers to be highly cost-effective. Given the current uncertainty of benefits,
      the harms from invasive testing, and the high costs associated with screening,
      direct-to-consumer marketing of helical CT is not advisable.

PMID- 12525233
TI  - Effect of exercise on total and intra-abdominal body fat in postmenopausal women:
      a randomized controlled trial.
AB  - CONTEXT: The increasing prevalence of obesity is a major public health concern.
      Physical activity may promote weight and body fat loss. OBJECTIVE: To examine the
      effects of exercise on total and intra-abdominal body fat overall and by level of
      exercise. DESIGN: Randomized controlled trial conducted from 1997 to 2001.
      SETTING AND PARTICIPANTS: A total of 173 sedentary, overweight (body mass index >
      or =24.0 and >33% body fat), postmenopausal women aged 50 to 75 years who were
      living in the Seattle, Wash, area. INTERVENTION: Participants were randomly
      assigned to an intervention consisting of exercise facility and home-based
      moderate-intensity exercise (n = 87) or a stretching control group (n = 86). MAIN
      OUTCOME MEASURE: Changes in body weight and waist and hip circumferences at 3 and
      12 months; total body, intra-abdominal, and subcutaneous abdominal fat at 12
      months. RESULTS: Twelve-month data were available for 168 women. Women in the
      exercise group participated in moderate-intensity sports/recreational activity
      for a mean (SD) of 3.5 (1.2) d/wk for 176 (91) min/wk. Walking was the most
      frequently reported activity. Exercisers showed statistically significant
      differences from controls in baseline to 12-month changes in body weight (-1.4
      kg; 95% confidence interval [CI], -2.5 to -0.3 kg), total body fat (-1.0%; 95%
      CI, -1.6% to -0.4%), intra-abdominal fat (-8.6 g/cm2; 95% CI, -17.8 to 0.9
      g/cm2), and subcutaneous abdominal fat (-28.8 g/cm2); 95% CI, -47.5 to -10.0
      g/cm2). A significant dose response for greater body fat loss was observed with
      increasing duration of exercise. CONCLUSIONS: Regular exercise such as brisk
      walking results in reduced body weight and body fat among overweight and obese
      postmenopausal women.

PMID- 12525234
TI  - Use of low-molecular-weight heparins in the management of acute coronary artery
      syndromes and percutaneous coronary intervention.
AB  - CONTEXT: Low-molecular-weight heparins (LMWHs) possess several potential
      pharmacological advantages over unfractionated heparin as an antithrombotic
      agent. OBJECTIVE: To systematically summarize the clinical data on the efficacy
      and safety of LMWHs compared with unfractionated heparin across the spectrum of
      acute coronary syndromes (ACSs), and as an adjunct to percutaneous coronary
      intervention (PCI). DATA SOURCES: We searched MEDLINE for articles from 1990 to
      2002 using the index terms heparin, enoxaparin, dalteparin, nadroparin,
      tinzaparin, low molecular weight heparin, myocardial infarction, unstable angina,
      coronary angiography, coronary angioplasty, thrombolytic therapy, reperfusion,
      and drug therapy, combination. Additional data sources included bibliographies of
      articles identified on MEDLINE, inquiry of experts and pharmaceutical companies,
      and data presented at recent national and international cardiology conferences.
      STUDY SELECTION: We selected for review randomized trials comparing LMWHs against
      either unfractionated heparin or placebo for treatment of ACS, as well as trials
      and registries examining clinical outcomes, pharmacokinetics, and/or
      phamacodynamics of LMWHs in the setting of PCI. Of 39 studies identified, 31
      fulfilled criteria for analysis. DATA EXTRACTION: Data quality was determined by
      publication in the peer-reviewed literature or presentation at an official
      cardiology society-sponsored meeting. DATA SYNTHESIS: The LMWHs are recommended
      by the American Heart Association and the American College of Cardiology for
      treatment of unstable angina/non-ST-elevation myocardial infarction. Clinical
      trials have demonstrated similar safety with LMWHs compared with unfractionated
      heparin in the setting of PCI and in conjunction with glycoprotein IIb/IIIa
      inhibitors. Finally, LMWHs show promise as an antithrombotic agent for the
      treatment of ST-elevation myocardial infarction. CONCLUSIONS: The LMWHs could
      potentially replace unfractionated heparin as the antithrombotic agent of choice
      across the spectrum of ACSs. In addition, they show promise as a safe and
      efficacious antithrombotic agent for PCI. However, further study is warranted to
      define the benefit of LMWHs in certain high-risk subgroups before their use can
      be universally recommended.

PMID- 12525235
TI  - Trends in community knowledge of the warning signs and risk factors for stroke.
AB  - CONTEXT: Poor public knowledge of stroke warning signs and risk factors limits
      effective stroke intervention and prevention. OBJECTIVE: To examine temporal
      trends in public knowledge of stroke warning signs and risk factors. DESIGN AND
      SETTING: Population-based random-digit telephone survey conducted in July
      November 2000 among individuals in the greater Cincinnati, Ohio, region.
      PARTICIPANTS: A total of 2173 survey respondents (69% response rate) were
      randomly identified based on their demographic similarities to the ischemic
      stroke population with regard to age, race, and sex. MAIN OUTCOME MEASURES:
      Spontaneous recall of at least 1 important stroke warning sign and 1 established
      stroke risk factor in comparison with findings from the same survey in 1995.
      RESULTS: In 2000, 70% of respondents correctly named at least 1 established
      stroke warning sign vs 57% in 1995 (P<.001), and 72% correctly named at least 1
      established stroke risk factor vs 68% in 1995. Groups of individuals with the
      highest risk and incidence of stroke, such as persons at least 75 years old,
      blacks, and men, were the least knowledgeable about warning signs and risk
      factors. Television was the most frequently cited source of knowledge, 32% in
      2000 vs 24% in 1995 (P<.001). CONCLUSIONS: Public knowledge of stroke warning
      signs within the greater Cincinnati region has significantly improved from 1995
      to 2000, although knowledge of stroke risk factors did not improve significantly
      during the same time period. Public education efforts must continue and should
      focus on groups at the highest risk of stroke.

PMID- 12525236
TI  - Does this patient have Parkinson disease?
AB  - CONTEXT: Diagnosis of Parkinson disease (PD) remains challenging. An accurate
      diagnosis is important because effective symptomatic treatment for PD is
      available. OBJECTIVE: To systematically review the literature for information on
      the precision and accuracy of the clinical examination for diagnosing PD. DATA
      SOURCES: MEDLINE database was searched for all English-language articles related
      to the diagnosis of PD published from January 1966 through April 2001. The
      reference lists of all articles retrieved were searched for additional relevant
      sources. STUDY SELECTION: Studies in which patients presented with 1 or more
      typical features of PD were included if the final diagnosis was confirmed by a
      suitable criterion standard and data could be extracted to determine the accuracy
      of 1 or more symptoms or signs. Variability in descriptions of symptoms and signs
      made it impossible to combine data across existing studies for most findings.
      DATA SYNTHESIS: We identified 6 studies that met our criteria. The positive
      (presence) likelihood ratios (LRs) for tremor as a symptom of PD ranged from 1.3
      to 17 (range of negative [absence] LRs, 0.24 to 0.60). Tremor as a sign of PD
      produced a range of positive LRs from 1.3 to 1.5 (negative LRs, 0.47 to 0.61).
      Clinical features useful in the diagnosis of PD include a history of the
      combination of symptoms of rigidity and bradykinesia (positive LR, 4.5; negative
      LR, 0.12); a history of loss of balance (range of positive LRs, 1.6 to 6.6; range
      of negative LRs, 0.29 to 0.35), symptoms of micrographia (range of positive LRs,
      2.8 to 5.9; range of negative LRs, 0.30 to 0.44), and a history of shuffling gait
      (range of positive LRs, 3.3 to 15; range of negative LRs, 0.32 to 0.50). Trouble
      with certain tasks such as turning in bed (positive LR, 13; negative LR, 0.56),
      opening jars (positive LR, 6.1; negative LR, 0.26), and rising from a chair
      (range of positive LRs, 1.9 to 5.2; range of negative LRs, 0.39 to 0.58). Useful
      signs include the glabella tap test (positive LR, 4.5; negative LR, 0.13),
      difficulty walking heel-to-toe (positive LR, 2.9; negative LR, 0.32), and
      rigidity (range of positive LRs, 0.53 to 2.8; range of negative LRs, 0.38 to
      1.6). Significant selection bias was detected in all studies included for review.
      CONCLUSIONS: Symptoms of tremor, rigidity, bradykinesia, micrographia, shuffling
      gait, and difficulty with the tasks of turning in bed, opening jars, and rising
      from a chair should be carefully reviewed in all patients with suspected PD. The
      glabella tap and heel-to-toe tests also should be assessed.

PMID- 12525237
TI  - Medicare quality improvement: bad apples or bad systems?

PMID- 12525238
TI  - Lung cancer screening at any price?

PMID- 12525243
TI  - Mechanisms of calcium disposal from osteoclastic resorption hemivacuole.
AB  - One of the most remarkable but neglected aspects of osteoclast function is its
      unique adaptation that allows the cell to function despite its resorbing surface
      being exposed to extremely high levels of ambient Ca2+. Recently our studies have
      provided evidence of continuous transcellular Ca2+ disposal, suggesting that
      osteoclasts are able to prevent Ca2+ accumulation within the resorptive
      hemivacuole. It has also been shown that matrix protein degradation products that
      accumulate within the osteoclast resorptive vacuole are also undergoing
      transcellular transport by transcytosis. However, both experimental evidence and
      theoretical considerations suggest that transcellular transport of Ca2+ and
      matrix protein is likely to occur via distinct routes. In light of these
      considerations, we are able to provide convincing explanations for the apparent
      anomalies of osteoclast intracellular [Ca2+] responses to a variety of endocrine
      stimuli. The understanding of the mechanisms involved in Ca2+ handling by
      osteoclasts indicates the lack of a simple link between osteoclast function and
      changes in overall cytosolic [Ca2+].

PMID- 12525244
TI  - TSH stimulates leptin secretion by a direct effect on adipocytes.
AB  - Leptin is a circulating hormone secreted by adipose tIssue which acts as a signal
      to the central nervous system where it regulates energy homeostasis and
      neuroendocrine processes. Although leptin modulates the secretion of several
      pituitary hormones, no information is available regarding a direct action of
      pituitary products on leptin release. However, it has been pointed out that
      leptin and TSH have a coordinated pulsatility in plasma. In order to test a
      direct action of TSH on in vitro leptin secretion, a systematic study of organ
      cultures of human omental adipose tIssue was performed in samples obtained at
      surgery from 34 patients of both sexes during elective abdominal surgery. TSH
      powerfully stimulated leptin secretion by human adipose tIssue in vitro. In
      contrast, prolactin, ACTH, FSH and LH were devoid of action. These results
      suggest that leptin and the thyroid axis maintain a complex and dual relationship
      and open the possibility that plasmatic changes in TSH may contribute to the
      regulation of leptin pulses.

PMID- 12525245
TI  - Reductions in adipose tissue and skeletal growth in rat adult offspring after
      prenatal leptin exposure.
AB  - Leptin is involved in regulating food intake, energy balance and bone formation.
      Increasing evidence suggests that leptin is also involved in fetal growth and
      development. The aim of this study was to determine if increased maternal leptin
      is followed by changes in body composition, skeletal growth or hormonal
      regulation in the adult rat offspring. Pregnant rats were given injections of
      either human recombinant leptin (3.5 mg/kg, i.p.) or vehicle on days 8, 10 and 12
      of gestation. Both genders of leptin-exposed offspring showed significantly
      reduced adipose tIssue weight at adult age. Skeletal growth and cortical bone
      dimensions were significantly reduced. Circulating testosterone levels were
      significantly increased in female leptin-exposed offspring, and male leptin
      exposed offspring had significant testicular enlargement. No significant effects
      were seen on circulating leptin levels or hypothalamic protein levels of the
      leptin receptor. The results demonstrate that maternally administered leptin is
      involved in fetal growth and development, leading to lean offspring with reduced
      skeletal growth.

PMID- 12525246
TI  - Influence of cortisol on adipose tissue development in the fetal sheep during
      late gestation.
AB  - The present study examined the extent to which the late gestation rise in fetal
      plasma cortisol influenced adipose tIssue development in the fetus. The effect of
      cortisol on the abundance of adipose tIssue mitochondrial proteins on both the
      inner (i.e. uncoupling protein (UCP)1) and outer (i.e. voltage-dependent anion
      channel (VDAC)) mitochondrial membrane, together with the long and short forms of
      the prolactin receptor (PRLR) protein and leptin mRNA was determined. Perirenal
      adipose tIssue was sampled from ovine fetuses to which (i) cortisol (2-3 mg/day
      for 5 days) or saline was infused up to 127-130 days of gestation, and (ii)
      adrenalectomised and intact controls at between 142 and 145 days of gestation
      (term=148 days). UCP1 protein abundance was significantly lower in
      adrenalectomised fetuses compared with age-matched controls, and UCP1 was
      increased by cortisol infusion and with gestational age. Adrenalectomy reduced
      the concentration of the long form of PRLR, although this effect was only
      significant for the highest molecular weight isoform. In contrast, neither the
      short form of PRLR, VDAC protein abundance or leptin mRNA expression was
      significantly affected by gestational age or cortisol status. Fetal plasma
      triiodothyronine concentrations were increased by cortisol and with gestational
      age, an affect abolished by adrenalectomy. When all treatment groups were
      combined, both plasma cortisol and triiodothyronine concentrations were
      positively correlated with UCP1 protein abundance. In conclusion, an intact
      adrenal is necessary for the late gestation rise in UCP1 protein abundance but
      cortisol does not appear to have a major stimulatory role in promoting leptin
      expression in fetal adipose tIssue. It remains to be established whether effects
      on UCP1 protein are directly regulated by cortisol alone or mediated by other
      anabolic fetal hormones such as triiodothyronine.

PMID- 12525247
TI  - Thyroxine and tri-iodothyronine differently affect uncoupling protein-1 content
      and antioxidant enzyme activities in rat interscapular brown adipose tissue.
AB  - The activity of the antioxidant enzymes copper-zinc superoxide dismutase
      (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as
      mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) activity, uncoupling
      protein-1 (UCP1) content, catecholamine degrading enzyme monoamine oxidase (MAO)
      activity and malonyl dialdehyde (MDA) concentration were studied in rat
      interscapular brown adipose tIssue (IBAT). Rats were treated with either
      thyroxine (T4) or tri-iodothyronine (T3) for five days and then exposed to cold
      (4 degrees C, 24 h) or housed at room temperature (22 degrees C). Under basal
      conditions, T3 treatment significantly increased UCP1 content and MnSOD activity
      whereas CuZnSOD, CAT and MAO activities were significantly decreased. Thyroxine
      treatment significantly decreased IBAT CAT activity while MDA levels markedly
      increased. Cold exposure induced a significant augmentation of UCP1 content and
      MnSOD and mGPDH activities only in animals that were rendered hyperthyroid by T4
      treatment. In T3-treated animals acutely exposed to cold stress, MDA
      concentration, an indicator of lipid peroxidation, was significantly higher
      compared with that of T3-treated animals housed at room temperature. However, in
      T4-treated animals, MDA concentrations were markedly lower. These results show
      that T4 and T3 differently affect IBAT parameters studied not only under basal
      but also under cold-stimulated conditions.

PMID- 12525248
TI  - Hypothyroidism alters the expression of Bcl-2 family genes to induce enhanced
      apoptosis in the developing cerebellum.
AB  - Thyroid hormone (TH) deficiency results in delayed proliferation and migration of
      cerebellar granule cells. Although extensive cell loss during the development of
      the cerebellum under hypothyroid conditions is known, its nature and its
      mechanism are poorly understood. Bcl-2 family gene expression is known to
      determine the fate of cells to undergo apoptosis. We evaluated the effect of
      hypothyroidism on Bcl-2 family gene expression in the developing rat cerebellum.
      Electrophoresis and Western blotting were used to analyze DNA fragmentation and
      expression of DNA fragmentation factor (DFF-45), Bcl-2, Bcl-xL and Bax genes
      respectively. In the hypothyroid condition, extensive DNA fragmentation and
      enhanced cleavage of DFF-45 were seen throughout development (postnatal day 0 to
      day 24) and adulthood whereas they were absent in the euthyroid state. The anti
      apoptotic genes Bcl-2 and Bcl-xL were down-regulated and the pro-apoptotic gene
      Bax was expressed at higher levels compared with the euthyroid state. These
      results suggest that normal levels of TH prevent cerebellar apoptosis to a large
      extent, whereas hypothyroidism not only increases the extent but also the
      duration of apoptosis by down-regulating the anti-apoptotic genes and maintaining
      a high level of the pro-apoptotic gene Bax.

PMID- 12525249
TI  - Myostatin expression during development and chronic stress in zebrafish (Danio
      rerio).
AB  - Myostatin, a member of the transforming growth factor-beta superfamily, is a
      negative regulator of skeletal muscle mass in mammals. We have studied myostatin
      expression during embryonic and post-hatching development in zebrafish by
      semiquantitative RT-PCR. The transcript is present in just-fertilized eggs and
      declines at 8 h post-fertilization (hpf), suggesting a maternal origin. A
      secondary rise occurs at 16 hpf, indicating the onset of embryonic transcription
      at the time of muscle cell differentiation. The level of myostatin mRNA decreases
      slightly at 24 hpf, when somitogenesis is almost concluded, and rises again at
      and after hatching, during the period of limited muscle hyperplastic growth that
      is typical of slow-growing, small fish. In the adult muscle, we found the highest
      expression of myostatin mRNA and protein, which were detectable by Northern and
      Western blot analyses respectively. Although only the precursor protein form was
      revealed in the adult lateral muscle, we demonstrated that zebrafish myostatin is
      proteolytically processed and secreted in cultured cells, as is its mammalian
      counterpart. These results suggest that myostatin may play an important
      regulatory role during myogenesis and muscle growth in fish, as it does in
      mammals. In chronically stressed fish, grown from 16 days post-fertilization to
      adulthood in an overcrowded environment, we observed both depression of body
      growth and a diminished level of myostatin mRNA in the adult muscle, as compared
      with controls. We propose that chronic stunting in fish brings about a general
      depression of muscle protein synthesis which does not spare myostatin.

PMID- 12525250
TI  - Residues in the C-terminal region of activin A determine specificity for
      follistatin and type II receptor binding.
AB  - Activin is a secreted growth factor that signals by binding two related classes
      of single transmembrane receptors at the cell surface. The interaction of activin
      with its receptors is highly regulated by other cell surface receptors,
      antagonistic ligands, and high affinity extracellular binding proteins such as
      follistatin. Two activin A mutants, the deletion mutant des[85-109]-activin A and
      the point mutant K102E-activin A (K102E), were investigated with respect to their
      ability to bind cell surface receptors and the binding protein follistatin. The
      deletion mutant exhibits low affinity for both receptors and follistatin whereas
      the point mutant fails to bind cell surface receptors but binds follistatin-288
      with high affinity. K102E is able to compete with wild type activin to bind to
      follistatin and can thus increase the concentration of activin available for
      receptor binding and signaling. These findings underline the importance of the C
      terminal region of activin for binding interactions and show that different
      residues in this region are involved in cell surface receptor and follistatin
      interactions.

PMID- 12525251
TI  - Transforming growth factor beta1 inhibits aldosterone and cortisol production in
      the human adrenocortical cell line NCI-H295R through inhibition of CYP11B1 and
      CYP11B2 expression.
AB  - Transforming growth factor beta1 (TGFbeta1) has been shown to exert strong
      inhibitory effects on adrenocortical cell steroidogenesis. However, the molecular
      targets of TGFbeta1 in adrenocortical cells appear to differ between species.
      Here, we report the first characterization of the regulatory effects of TGFbeta1
      on the steroidogenic functions of the human adrenocortical tumor cell line NCI
      H295R. After treatment with 2 ng/ml TGFbeta1 for 24 h, basal production of
      corticosterone, cortisol and androstenedione was dramatically decreased. When
      TGFbeta1 was added simultaneously with forskolin, the production of cortisol and
      11-hydroxyandrostenedione was decreased by 85% whereas that of deoxycortisol was
      increased. When TGFbeta1 was added simultaneously with angiotensin II,
      aldosterone production was reduced by 80%. We observed that TGFbeta1 strongly
      inhibits forskolin-induced steroid 11beta-hydroxylase activity and CYP11B1 mRNA
      levels, as well as angiotensin II-induced aldosterone synthase activity and
      CYP11B2 mRNA levels. CYP11B1 and CYP11B2 gene products thus appear as the major
      steroidogenic enzymes down-regulated by TGFbeta1 in the human adrenocortical
      tumor cell line NCI-H295R.

PMID- 12525252
TI  - Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter
      transcription factor II (COUP-TFII) expression in human breast cancer cell lines.
AB  - Growth factors are essential for cellular growth and differentiation in both
      normal and malignant human breast epithelial cells. In the present study we
      investigated the effect of epidermal growth factor (EGF), transforming growth
      factor alpha (TGFalpha) and phorbol myristate acetate (PMA) on chicken ovalbumin
      upstream promoter-transcription factor (COUP-TF) expression in human breast
      cancer cells. The orphan receptors COUP-TFI and COUP-TFII are members of the
      nuclear receptor superfamily. The high degree of evolutionary conservation of
      these proteins strongly argues for an important biological function. COUP-TF
      expression was highest in SK-BR3 cells (approximately 130 amol/ micro g total
      RNA), while the lowest COUP-TF expression was observed in MCF-7 cells (3.5 amol/
      micro g total RNA). While treatment of EGF, TGFalpha and PMA induced expression
      of COUP-TFII, COUP-TFI did not respond to these agents. Oncostatin M (OSM) is
      known to exert an antiproliferative effect in breast cancer cells. Treatment of
      MCF-7 cells with OSM resulted in an approximately 90% reduction of COUP-TFII mRNA
      expression. In SK-BR3 cells, treatment with the MEK inhibitor UO126 resulted in a
      profound suppression of endogenous COUP-TFII expression. Furthermore, cotreatment
      with UO126 prevented induction of COUP-TFII expression by EGF in MCF-7 cells. In
      conclusion, our data provide evidence, for the first time, that mitogenic
      substances which activate the MAP kinase pathway, can induce COUP-TFII
      expression. Our results strongly suggest that an active MAP kinase pathway is
      essential for COUP-TFII expression in human breast cancer cells.

PMID- 12525253
TI  - Adrenomedullin expression and function in the rat carotid body.
AB  - Adrenomedullin (AM) immunoreactivity has been found in granules of the glomus
      (type I) cells of the carotid bodies in rats. The identity of these cells was
      ascertained by colocalization of immunoreactivities for AM and tyrosine
      hydroxylase in their cytoplasm. Exposure of freshly isolated carotid bodies to
      synthetic AM resulted in a concentration- and time-dependent degranulation of
      glomus cells as measured by dopamine (DA) release. DA release reached a zenith 30
      min after exposure to AM (94.2% over untreated controls). At this time-point, the
      response to AM was similar to the one elicited by 5 min of exposure to 100 mM K+.
      Nevertheless, injection of 1 micro l 60 nM AM/g body weight into the tail vein of
      the rats did not induce statistical differences in DA release from the carotid
      bodies. Exposure of the oxygen-sensitive cell line PC-12 to hypoxia elicited an
      increase in AM mRNA expression and peptide secretion into serum-free conditioned
      medium. Previous data have shown that elevation of AM expression under hypoxia is
      mediated through hypoxia-inducible factor-1, and that exposure of chromaffin
      cells to AM results in degranulation. All these data suggest that AM is an
      important autocrine regulator of carotid body function.

PMID- 12525254
TI  - Macrophage migration inhibitory factor expression is increased in pituitary
      adenoma cell nuclei.
AB  - Macrophage migration inhibitory factor (MIF) is an essential regulator of the
      macrophage responses to endotoxin. MIF also has the ability to override the anti
      inflammatory actions of glucocorticoids during an immune response, and is thus an
      important pro-inflammatory factor. The presence of MIF in cells of the anterior
      pituitary has been described, and high levels of MIF in other rapidly
      proliferating tIssues have also been demonstrated. It has been hypothesised that
      MIF release from these cells is influenced by the hypothalamo-pituitary-adrenal
      axis, and that ACTH and MIF are released simultaneously to exert counter
      regulatory effects on cortisol. However, another intracellular role for MIF has
      also been suggested as it has been shown that MIF exerts an effect on the
      inhibitory cell cycle control protein p27 through an interaction with Jab1, a
      protein implicated in p27 degradation. We studied MIF expression in different
      normal and adenomatous human pituitary samples using immunohistochemistry and RT
      PCR. There was evidence of co-immunoprecipitation of MIF with Jab1, suggesting an
      interaction of the two proteins. Our results showed that there is increased
      expression of MIF protein in the nuclei of all pituitary adenomas compared with
      normal tIssue (P=0.0067), but there was no statistically significant difference
      in nuclear MIF expression between the different adenoma types. Nuclear MIF
      expression correlated positively with p27 and its phosphorylated form in normal
      tIssue (P=0.0028 and P<0.0001); however, this relationship was not seen in the
      adenoma samples. Cytoplasmic expression of MIF was found to be variable both in
      normal and adenomatous samples, with no consistent pattern. MIF mRNA was
      demonstrated to be present in all tumour and normal samples studied. Somatotroph
      tumours showed higher MIF mRNA expression compared with normal pituitary or other
      types of adenomas. In conclusion, MIF is expressed in cell nuclei in pituitary
      adenomas to a greater extent than in normal pituitary tIssue. We speculate that
      it may play a role in the control of the cell cycle, but whether its higher level
      in adenomas is a cause or a consequence of the tumorigenic process remains to be
      clarified.

PMID- 12525255
TI  - Neurohypophysial hormone regulation of Cl- secretion: physiological evidence for
      V1-type receptors in sea bass gill respiratory cells in culture.
AB  - Neurohypophysial hormone receptors were studied in primary cultures of sea bass
      (Dicentrarchus labrax) gill respiratory-like cells grown on permeable supports.
      This preparation was previously shown to provide a functional model for
      investigating the hormonal regulation of Cl- secretion. Under control conditions,
      the cultured monolayered epithelium had a short-circuit current (ISC) of 3.5+/
      1.1 micro A x cm(-2). This current had previously been identified as an active Cl
      secretion. The addition of increasing concentrations of the fish
      neurohypophysial hormones, arginine vasotocin (AVT) or isotocin (IT), elicited a
      concentration-dependent stimulation of the ISC. Maximal increases of 60.9+/-12.1%
      and 117.7+/-28.0% above the basal ISC value were obtained for 10(-7) M AVT and IT
      respectively. Half-maximal effects were obtained for 3.1 x 10(-9) M AVT and for
      1.4 x 10(-9) M IT. Mucosal application of 1.0 mM diphenylalamine-2-carboxylic
      acid (a specific blocker of Cl- channels) after serosal addition of 5 x 10(-8) M
      AVT or IT inhibited not only the basal but also the stimulated current, revealing
      a correlation with a hormone-dependent Cl- transport. Specific V1 or V2 receptor
      analogues of vasopressin (mammalian hormone) were used to characterize the type
      of neurohypophysial hormone receptors pharmacologically. While the V1 agonist
      [Phe2,Orn8]-oxytocin stimulated the basal Cl- secretion with a similar profile to
      that of AVT or IT, the V2 agonist [Deamino1,Val4,d -Arg8]-vasopressin had no
      effect. The V1 antagonist [d(CH2)5 1,O-Me-Tyr2,Arg8]-vasopressin used at a
      concentration of 5 x 10(-7) M totally reversed the 10-8 M AVT-stimulated Cl-
      secretion, whereas the V2 antagonist [d(CH2)5 1,d -Ile2,Ile4,Arg8,Ala9]
      vasopressin used at the same concentration had no significant effect. In
      contrast, similar experiments carried out in the presence of 10(-8) M IT showed
      that both antagonists significantly reduced the IT-stimulated Cl- secretion, with
      the efficiency of the V1 receptor antagonist being significantly greater than
      that of the V2. This study provides evidence for neurohypophysial hormone control
      of Cl- secretion in fish cultured gill respiratory cells. It suggests that on a
      physiological basis the hormonal effect is shared by the two peptides present in
      fish neurohypophysis (AVT and IT), acting by means of two distinct, although
      pharmacologically similar, V1-type receptors (according to the mammalian
      classification). These specific receptors are expected to play an important role
      in controlling ion homeostasis in seawater fish.

PMID- 12525256
TI  - Insulin-like growth factor and insulin receptors in intestinal mucosa of neonatal
      calves.
AB  - Intestinal development is modified by age and nutrition, mediated in part by
      insulin-like growth factors (IGF-I, IGF-II) and insulin. We have investigated
      whether expression of IGF-I, IGF-II and insulin receptors (IGF-IR, IGF-IIR and
      IR; measured by real-time RT-PCR) and binding capacity (Bmax) of IGF-IR, IGF-IIR
      and IR in the mucosa of the small and large intestine of neonatal calves are
      modified by age and different feeding regimes. In experiment 1, pre-term (GrP)
      and full-term (GrN) calves (after 277 and 290 days of pregnancy respectively)
      were killed immediately after birth before being fed; a further group of full
      term calves were fed for 7 days and killed on day 8 of life (GrC(1-3)). In
      experiment 2, full-term calves were killed on day 8 after being fed first
      colostrum for 7 days (GrCmax), colostrum of the first six milkings for 3 days
      (GrC(1-3)) or milk-based formula for 3 days (GrF(1-3)). Intestinal sites differed
      with respect to expression levels of IGF-IR (duodenum>jejunum in GrC(1-3);
      ileum>colon, duodenum> or = jejunum in GrF(1-3)), IGF-IIR (colon>duodenum and
      ileum in GrN), and IR (lowest in ileum in GrP and CrN; highest in colon in GrC(1
      3) and GrCmax). They also differed with respect to Bmax of IGF-IR (ileum and
      colon>duodenum and jejunum in GrP; ileum and colon>jejunum in GrN; colon>jejunum
      in GrC(1-3); lowest in jejunum in GrF(1-3)), IGF-IIR (duodenum and colon>jejunum
      and ileum in GrP; duodenum>ilem and colon>jejunum in GrN; duodenum, jejunum and
      colon>ileum in GrCmax, GrC(1-3), and GrF(1-3)) and IR (ileum>duodenum, jejunum
      and colon in GrCmax, GrC(1-3), and GrF(1-3)). There were significant differences
      between groups in the expression of IGF-IR (GrF(1-3)> GrCmax and GrC(1-3) in
      ileum), IGF-IIR (GrN>GrP and GrC(1-3) in colon; GrN>GrC(1-3) in jejunum and total
      intestine), and IR (GrCmax>GrF(1-3) in colon) and in the Bmax of IGF-IR (GrP>GrN
      in colon; GrCmax>GrF(1-3) in jejunum), IGF-IIR (GrN>GrP in duodenum, ileum and
      total intestine; GrN>GrC(1-3) in duodenum, ileum, colon and total intestine) and
      IR (GrN>GrP in total intestine; GrC(1-3)>GrN in ileum and total intestine). In
      addition, Bmax values of IGF-IR, IGF-IIR and IR were correlated with villus
      circumference, villus height/crypt depth and proliferation rate of crypt cells at
      various intestinal sites. There were marked differences in Bmax of IGF-IR, IGF
      IIR and IR dependent on mRNA levels, indicating that differences in Bmax were the
      consequence of differences in posttranslational control and of receptor turnover
      rates. In conclusion IGF-IR, IGF-IIR and IR expressions and Bmax in intestinal
      mucosa were different at different intestinal sites and were variably affected by
      age, but not significantly affected by differences in nutrition. Receptor
      densities were selectively associated with intestinal mucosa growth.

PMID- 12525257
TI  - Improved biological activity of Gly2- and Ser2-substituted analogues of glucose
      dependent insulinotrophic polypeptide.
AB  - The therapeutic potential of glucagon-like peptide-1 (GLP-1) in improving
      glycaemic control in diabetes has been widely studied, but the potential
      beneficial effects of glucose-dependent insulinotropic polypeptide (GIP) have
      until recently been almost overlooked. One of the major problems, however, in
      exploiting either GIP or GLP-1 as potential therapeutic agents is their short
      duration of action, due to enzymatic degradation in vivo by dipeptidylpeptidase
      IV (DPP IV). Therefore, this study examined the plasma stability, biological
      activity and antidiabetic potential of two novel NH2-terminal Ala2-substituted
      analogues of GIP, containing glycine (Gly) or serine (Ser). Following incubation
      in plasma, (Ser2)GIP had a reduced hydrolysis rate compared with native GIP,
      while (Gly2)GIP was completely stable. In Chinese hamster lung fibroblasts stably
      transfected with the human GIP receptor, GIP, (Gly2)GIP and (Ser2)GIP stimulated
      cAMP production with EC(50) values of 18.2, 14.9 and 15.0 nM respectively. In the
      pancreatic BRIN-BD11 beta-cell line, (Gly2)GIP and (Ser2)GIP (10(-8) M) evoked
      significant increases (1.2- and 1.5-fold respectively; P<0.01 to P<0.001) in
      insulinotropic activity compared with GIP. In obese diabetic ob/ob mice, both
      analogues significantly lowered (P<0.001) the glycaemic excursion in response to
      i.p. glucose. This enhanced glucose-lowering ability was coupled to a
      significantly raised (P<0.01) and more protracted insulin response compared with
      GIP. These data indicate that substitution of the penultimate Ala2 in GIP by Gly
      or Ser confers resistance to plasma DPP IV degradation, resulting in enhanced
      biological activity, therefore raising the possibility of their use in the
      treatment of type 2 diabetes.

PMID- 12525258
TI  - Establishment of T cell lines to bovine beta-casein and beta-casein-derived
      epitopes in patients with type 1 diabetes.
AB  - Enhanced cellular immune response to bovine beta-casein has been reported in
      patients with type 1 diabetes. In this study we aimed to establish beta-casein
      specific T cell lines from newly diagnosed type 1 diabetic patients and to
      characterise these cell lines in terms of phenotype and epitope specificity.
      Furthermore, since sequence homologies exist between beta-casein and putative
      beta-cell autoantigens, reactivity to the latter was also investigated. T cell
      lines were generated from the peripheral blood of nine recent onset type 1
      diabetic patients with different HLA-DQ and -DR genotypes, after stimulation with
      antigen pulsed autologous irradiated antigen presenting cells (APCs) and
      recombinant human interleukin-2 (rhIL-2). T cell line reactivity was evaluated in
      response to bovine beta-casein, to 18 overlapping peptides encompassing the whole
      sequence of beta-casein and to beta-cell antigens, including the human insulinoma
      cell line, CM, and a peptide from the beta-cell glucose transporter, GLUT-2. T
      cell lines specific to beta-casein could not be isolated from HLA-matched and 
      unmatched control subjects. beta-Casein T cell lines reacted to different
      sequences of the protein, however a higher frequency of T cell reactivity was
      observed towards the C-terminal portion (peptides B05-14, and B05-17 in 5/9 and
      4/9 T cell lines respectively). Furthermore, we found that 1 out of 9 beta-casein
      specific T cell lines reacted also to the homologous peptide from GLUT-2, and
      that 3 out of 4 of tested cell lines reacted also to extracts of the human
      insulinoma cell line, CM. We conclude that T cell lines specific to bovine beta
      casein can be isolated from the peripheral blood of patients with type 1
      diabetes; these cell lines react with multiple and different sequences of the
      protein particularly towards the C-terminal portion. In addition, reactivity of
      beta-casein T cell lines to human insulinoma extracts and GLUT-2 peptide was
      detected, suggesting that the potential cross-reactivity with beta-cell antigens
      deserves further investigation.

PMID- 12525259
TI  - Evaluation of relative roles of LH and FSH in regulation of differentiation of
      Leydig cells using an ethane 1,2-dimethylsulfonate-treated adult rat model.
AB  - The relative role of LH and FSH in regulation of differentiation of Leydig cells
      was assessed using an ethane 1,2-dimethylsulfonate (EDS)-treated rat model in
      which endogenous LH or FSH was neutralized from day 3 to day 22 following EDS
      treatment. Serum testosterone and the in vitro response of the purified Leydig
      cells to human chorionic gonadotropin (hCG) was monitored. In addition RNA was
      isolated from the Leydig cells to monitor the steady-state mRNA levels by RT-PCR
      for 17alpha-hydroxylase, side chain cleavage enzyme, steroidogenic acute
      regulatory protein (StAR), LH receptor, estrogen receptor (ER-alpha) and
      cyclophilin (internal control). Serum testosterone was undetected and the
      isolated Leydig cells secreted negligible amount of testosterone on stimulation
      with hCG in the group of rats that were treated with LH antiserum following EDS
      treatment. RT-PCR analysis revealed the absence of message for cholesterol side
      chain cleavage enzyme and 17alpha-hydroxylase although ER-alpha and LH receptor
      mRNA could be detected, indicating the presence of undifferentiated precursor
      Leydig cells. In contrast, the effects following deprival of endogenous FSH were
      not as drastic as seen following LH neutralization. Deprival of endogenous FSH in
      EDS-treated rats led to a significant decrease in serum testosterone and in vitro
      response to hCG by the Leydig cells. Also, there was a significant decrease in
      the steady-state mRNA levels of 17alpha-hydroxylase, cholesterol side chain
      cleavage enzyme, LH receptor and StAR as assessed by a semiquantitative RT-PCR.
      These results establish that while LH is obligatory for the functional
      differentiation of Leydig cells, repopulation of precursor Leydig cells is
      independent of LH, and also unequivocally establish an important role for FSH in
      regulation of Leydig cell function.

PMID- 12525260
TI  - Effect of Lepidium meyenii (Maca), a root with aphrodisiac and fertility
      enhancing properties, on serum reproductive hormone levels in adult healthy men.
AB  - Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between
      4000 and 4500 m in the central Andes. Maca is traditionally employed in the
      Andean region for its supposed aphrodisiac and/or fertility-enhancing properties.
      This study was a 12-week double-blind, placebo-controlled, randomized, parallel
      trial in which active treatment with different doses of Maca Gelatinizada was
      compared with a placebo. The study aimed to test the hypothesis that Maca has no
      effect on serum reproductive hormone levels in apparently healthy men when
      administered in doses used for aphrodisiac and/or fertility-enhancing properties.
      Men aged between 21 and 56 Years received 1500 mg or 3000 mg Maca. Serum levels
      of luteinizing hormone, follicle-stimulating hormone, prolactin, 17-alpha
      hydroxyprogesterone, testosterone and 17-beta estradiol were measured before and
      at 2, 4, 8 and 12 weeks of treatment with placebo or Maca (1.5 g or 3.0 g per
      day). Data showed that compared with placebo Maca had no effect on any of the
      hormones studied nor did the hormones show any changes over time. Multiple
      regression analysis showed that serum testosterone levels were not affected by
      treatment with Maca at any of the times studied (P, not significant). In
      conclusion, treatment with Maca does not affect serum reproductive hormone
      levels.

PMID- 12525261
TI  - An automated method for finding molecular complexes in large protein interaction
      networks.
AB  - BACKGROUND: Recent advances in proteomics technologies such as two-hybrid, phage
      display and mass spectrometry have enabled us to create a detailed map of
      biomolecular interaction networks. Initial mapping efforts have already produced
      a wealth of data. As the size of the interaction set increases, databases and
      computational methods will be required to store, visualize and analyze the
      information in order to effectively aid in knowledge discovery. RESULTS: This
      paper describes a novel graph theoretic clustering algorithm, "Molecular Complex
      Detection" (MCODE), that detects densely connected regions in large protein
      protein interaction networks that may represent molecular complexes. The method
      is based on vertex weighting by local neighborhood density and outward traversal
      from a locally dense seed protein to isolate the dense regions according to given
      parameters. The algorithm has the advantage over other graph clustering methods
      of having a directed mode that allows fine-tuning of clusters of interest without
      considering the rest of the network and allows examination of cluster
      interconnectivity, which is relevant for protein networks. Protein interaction
      and complex information from the yeast Saccharomyces cerevisiae was used for
      evaluation. CONCLUSION: Dense regions of protein interaction networks can be
      found, based solely on connectivity data, many of which correspond to known
      protein complexes. The algorithm is not affected by a known high rate of false
      positives in data from high-throughput interaction techniques. The program is
      available from ftp://ftp.mshri.on.ca/pub/BIND/Tools/MCODE.

PMID- 12525262
TI  - Building the national health information infrastructure for personal health,
      health care services, public health, and research.
AB  - BACKGROUND: Improving health in our nation requires strengthening four major
      domains of the health care system: personal health management, health care
      delivery, public health, and health-related research. Many avoidable shortcomings
      in the health sector that result in poor quality are due to inaccessible data,
      information, and knowledge. A national health information infrastructure (NHII)
      offers the connectivity and knowledge management essential to correct these
      shortcomings. Better health and a better health system are within our reach.
      DISCUSSION: A national health information infrastructure for the United States
      should address the needs of personal health management, health care delivery,
      public health, and research. It should also address relevant global dimensions
      (e.g., standards for sharing data and knowledge across national boundaries). The
      public and private sectors will need to collaborate to build a robust national
      health information infrastructure, essentially a 'paperless' health care system,
      for the United States. The federal government should assume leadership for
      assuring a national health information infrastructure as recommended by the
      National Committee on Vital and Health Statistics and the President's Information
      Technology Advisory Committee. Progress is needed in the areas of funding,
      incentives, standards, and continued refinement of a privacy (i.e.,
      confidentiality and security) framework to facilitate personal identification for
      health purposes. Particular attention should be paid to NHII leadership and
      change management challenges. SUMMARY: A national health information
      infrastructure is a necessary step for improved health in the U.S. It will
      require a concerted, collaborative effort by both public and private sectors.

PMID- 12525263
TI  - Airborne rhinovirus detection and effect of ultraviolet irradiation on detection
      by a semi-nested RT-PCR assay.
AB  - BACKGROUND: Rhinovirus, the most common cause of upper respiratory tract
      infections, has been implicated in asthma exacerbations and possibly asthma
      deaths. Although the method of transmission of rhinoviruses is disputed, several
      studies have demonstrated that aerosol transmission is a likely method of
      transmission among adults. As a first step in studies of possible airborne
      rhinovirus transmission, we developed methods to detect aerosolized rhinovirus by
      extending existing technology for detecting infectious agents in nasal specimens.
      METHODS: We aerosolized rhinovirus in a small aerosol chamber. Experiments were
      conducted with decreasing concentrations of rhinovirus. To determine the effect
      of UV irradiation on detection of rhinoviral aerosols, we also conducted
      experiments in which we exposed aerosols to a UV dose of 684 mJ/m2. Aerosols were
      collected on Teflon filters and rhinovirus recovered in Qiagen AVL buffer using
      the Qiagen QIAamp Viral RNA Kit (Qiagen Corp., Valencia, California) followed by
      semi-nested RT-PCR and detection by gel electrophoresis. RESULTS: We obtained
      positive results from filter samples that had collected at least 1.3 TCID50 of
      aerosolized rhinovirus. Ultraviolet irradiation of airborne virus at doses much
      greater than those used in upper-room UV germicidal irradiation applications did
      not inhibit subsequent detection with the RT-PCR assay. CONCLUSION: The air
      sampling and extraction methodology developed in this study should be applicable
      to the detection of rhinovirus and other airborne viruses in the indoor air of
      offices and schools. This method, however, cannot distinguish UV inactivated
      virus from infectious viral particles.

PMID- 12525264
TI  - Relationship between craving and personality in treatment-seeking women with
      substance-related disorders.
AB  - BACKGROUND: Individual differences may impact susceptibility to addiction. The
      impact of personality features on drug craving, however, has not been studied,
      particularly in women. METHODS: Ninety-five treatment-seeking women with
      substance dependence, abstinent for at least 5 and no more than 21 days, were
      investigated regarding the correlation between personality factors and craving.
      Personality was assessed using the Temperament and Character Inventory (TCI), the
      NEO Personality Inventory Revised (NEO-PI-R), and the Barratt Impulsiveness Scale
      version 11 (BIS-11). Cravings were assessed through the Pennsylvania Craving
      Scale (PCS), and the Craving Questionnaire (CQ). Anxiety and depressive
      symptomatology were also recorded. RESULTS: Craving scores were positively
      correlated with depression and negatively correlated with number of days
      abstinent from substance use. Also, craving scores were positively associated
      with the novelty-seeking factor from the TCI and the total score on the BIS-11,
      and negatively associated with the conscientiousness and agreeableness facets of
      the NEO-PI-R. CONCLUSION: Findings suggest that personality features,
      particularly impulsiveness, can be important predictors of craving in women,
      which has important implications for treatment planning.

PMID- 12525265
TI  - Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are
      increased in combination with the polyamine putrescine in the SW480 colon tumour
      cell line.
AB  - BACKGROUND: Many tumours undergo disregulation of polyamine homeostasis and
      upregulation of ornithine decarboxylase (ODC) activity, which can promote
      carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC
      activity by difluoromethylornithine (DFMO) has been shown to reduce the number
      and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown
      promising chemopreventive activity against a range of human tumour cell types,
      but little is known about the effect of this agent on colon cell lines. Here, we
      investigated whether inhibition of ODC by I3C could contribute to a
      chemopreventive effect in colon cell lines. METHODS: Cell cycle progression and
      induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase
      activity was determined by liberation of CO2 from 14C-labelled substrate, and
      polyamine levels were measured by HPLC. RESULTS: I3C inhibited proliferation of
      the human colon tumour cell lines HT29 and SW480, and of the normal tissue
      derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells.
      The agent also caused a decrease in ODC activity in a dose-dependent manner.
      While administration of exogenous putrescine reversed the growth-inhibitory
      effect of DFMO, it did not reverse the growth-inhibition following an I3C
      treatment, and in the case of the SW480 cell line, the effect was actually
      enhanced. In this cell line, combination treatment caused a slight increase in
      the proportion of cells in the G2/M phase of the cell cycle, and increased the
      proportion of cells undergoing necrosis, but did not predispose cells to
      apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine
      levels, which was not modulated by putrescine co-administration. CONCLUSION:
      While indole-3-carbinol decreased ornithine decarboxylase activity in the colon
      cell lines, it appears unlikely that this constitutes a major mechanism by which
      the agent exerts its antiproliferative effect, although accumulation of spermine
      may cause cytotoxicity and contribute to cell death. The precise mechanism by
      which putrescine enhances the growth inhibitory effect of the agent remains to be
      elucidated, but does result in cells undergoing necrosis, possibly following
      accumulation in the G2/M phase of the cell cycle.

PMID- 12525266
TI  - Opioids: a review.
AB  - Recent discoveries in opioid pharmacology help explain the enormous variability
      in clinical responses to these powerful analgesics. Although there is only one m
      opioid receptor gene, splice variants of that gene's expression result in a
      panoply of different functioning receptors. Other sources of variable response
      include polymorphisms in the m opioid receptor regulatory region, and
      pharmacokinetic differences because of cytochrome P-450 mono-oxygenase
      heterogeneity. Analgesic tolerance is likely the key phenomenon limiting the
      benefit of opioids. A plethora of intracellular pathways affects this. Among them
      are the N-methyl-D-aspartate receptor, protein kinase C gamma activity, nitric
      oxide synthase, and GM1 ganglioside content of the neuronal membrane. Clinical
      studies undercut the routine use of meperidine in most settings. Other studies
      have shown better ways to diminish opioid side effects.

PMID- 12525267
TI  - Antidepressants for chronic neuropathic pain.
AB  - Tricyclic antidepressants have been used to manage pain for several decades, and
      are superior treatments for some patients suffering from neuropathic pain.
      Unfortunately, older antidepressants have dose-limiting side effects that can
      lead to drug intolerance. The most common are anticholinergic side effects,
      although some patients experience sexual dysfunction. Cognitive impairment,
      sedation, and orthostatic hypotension also are relatively common. Taking an
      overdose of tricyclic antidepressants can be lethal in overdose. Several weeks of
      therapy may be required before antinociception occurs, but tricyclic
      antidepressants in optimal doses appear to be the most effective treatment for
      neuropathic pain; this is supported by systematic reviews comparing them with
      other agents. Newer medications such as atypical antidepressants and
      anticonvulsants may be overtaking older antidepressants, but they should not be
      overlooked as important options for the management of pain.

PMID- 12525268
TI  - Targeted topical peripheral analgesics in the management of pain.
AB  - The term "targeted peripheral analgesics" has been developed to describe
      analgesics whose mechanism of action appears to be primarily through reducing
      pain transmission within the peripheral nervous system. Key differences between
      targeted peripheral and systemic analgesics and the difference between topical
      and transdermal analgesics are discussed. A review of the clinical conditions
      that have reportedly responded to targeted peripheral analgesics is described in
      detail in this article.

PMID- 12525269
TI  - Anticonvulsants for the treatment of neuropathic pain syndromes.
AB  - This article is an evidence-based summary of randomized clinical trials published
      in peer-reviewed journals regarding the efficacy of anticonvulsants for the
      treatment of neuropathic pain.

PMID- 12525270
TI  - N-methyl-D-aspartate- enhanced analgesia.
AB  - A greater understanding of the mechanisms that produce chronic pain states has
      led to a search for novel agents with the potential to produce analgesia by
      directly modulating specific processes involved in the transduction,
      transmission, modulation, perception, and encoding of pain. It is hoped that
      compounds directed at these specific targets will produce better analgesics with
      an improved side-effect profile. The N-methyl-D-aspartate receptor has been shown
      to play an important role in pain modulation and has become a target for
      potential analgesic compounds. Antagonists to the N-methyl-D-aspartate receptor
      were antinociceptive in a number of animal models, and analgesic in experimental
      pain models in healthy subjects and in chronic neuropathic pain syndromes. In
      addition, these compounds have demonstrated the ability to prevent the
      development of tolerance to opioid analgesic therapy. This has led to
      investigations of therapies that combine an opioid agonist with an N-methyl-D
      aspartate receptor antagonist.

PMID- 12525271
TI  - Antidepressants in the treatment of migraine headache.
AB  - Antidepressants, particularly tricyclic antidepressants, have been a mainstay in
      the prophylactic therapy of migraine. The tricyclic antidepressants
      amitriptyline, nortriptyline, and doxepin have been the major agents for
      prophylactic treatment of migraine. These cause significant side effects in some
      patients. The high-affinity selective serotonin reuptake inhibitors and other
      newer antidepressants have been disappointing and much less effective in the
      treatment of migraine. In patients who are depressed with severe migraine, a
      tricyclic antidepressant may treat both conditions; however, the addition of a
      newer atypical antidepressant may be needed.

PMID- 12525272
TI  - Ergotamine and dihydroergotamine: a review.
AB  - The ergot alkaloids were the first specific antimigraine therapy available.
      However, with the advent of the triptans, their use in the treatment of migraine
      has declined and their role has become less clear. This review discusses the
      pharmacology, efficacy, and safety of the ergots. In randomized clinical trials,
      oral ergotamine was found to be superior to placebo, but inferior to 100 mg of
      oral sumatriptan. In contrast, rectal ergotamine was found to have higher
      efficacy (73% headache relief) than rectal sumatriptan (63% headache relief).
      Intranasal dihydroergotamine was found to be superior to placebo, but less
      effective than subcutaneous and intranasal sumatriptan. Ergotamine is still
      widely used in some countries for the treatment of severe migraine attacks. It is
      generally regarded as a safe and useful drug if prescribed for infrequent use, in
      the correct dose, and in the absence of contraindications; however, safer and
      more effective options do exist in the triptans. In patients with status
      migrainous and patients with frequent headache recurrence, ergotamine is still
      probably useful.

PMID- 12525273
TI  - The role of anticonvulsants in preventive migraine therapy.
AB  - The mainstay of migraine treatment is pharmacotherapy. There have been numerous
      medications used to prevent migraine headaches, including b-blockers, calcium
      channel blockers, anticonvulsants, and nonsteroidal anti-inflammatory drugs.
      Sodium valproate is the only antiepileptic drug approved by the Food and Drug
      Administration for migraine prevention. Newer antiepileptics, including
      gabapentin and topiramate, are being evaluated for their role in preventive
      therapy. The mechanism of action of antiepileptics is not fully understood, but
      they all share a common role in enhancing gamma-aminobutyric acid-mediated
      inhibition. This article reviews the role of anticonvulsants in preventive
      migraine therapy.

PMID- 12525274
TI  - Opioid resistance in chronic daily headache: a synthesis of ideas from the bench
      and bedside.
AB  - Chronic daily headache is a complex pain disorder that encompasses many
      diagnostic and therapeutic challenges. Our understanding of the pathophysiologic
      processes of intermittent migraine has improved over the past decade, but the
      biologic basis of chronic daily headache remains obscure. Some of the more common
      issues confounding management of patients who experience chronic daily headache
      are medication overuse, psychiatric comorbidity, refractoriness to pharmacologic
      treatments, and disability. Long-acting opioid analgesics would appear to provide
      a viable treatment option for those patients who remain refractory to other
      treatment interventions; however, clinical experience often does not support this
      belief. Current concepts of the pathophysiologic basis of chronic pain and
      associated neural plasticity may elucidate a biologic basis for the general
      inefficacy of opioids in the management of chronic daily headache. This article
      explores the models of pathophysiology for migraine and chronic daily headache,
      the concept of chronic daily headache as a neuropathic pain syndrome, neural
      plasticity in the context of neuropathic pain states, the physiologic basis for
      opioid tolerance and opioid-induced hyperalgesia, and how each of these
      conditions interact to provoke the general lack of opioid efficacy often observed
      in the management of chronic daily headache.

PMID- 12525275
TI  - Oropharyngeal cancer: the role of chemotherapy.
AB  - Successful management of squamous cell cancer of the oropharynx must address two,
      sometimes conflicting, treatment goals. The first goal is disease eradication,
      and the second is preservation of oropharyngeal function. For early cancers,
      definitive surgical excision often represents the most effective and least morbid
      approach. When surgery is likely to result in functional deficits of speech or
      swallowing, definitive radiation therapy can also be used successfully. Often the
      choice of treatment modality is based on institutional expertise and bias.
      However, for the more frequent patients with advanced disease, treatment choices
      become more complex. Historically, surgery and radiation therapy have been used
      together, often with suboptimal control of locoregional disease and significant
      long-term functional deficits, reflecting surgical excision, radiation-induced
      long-term toxicities, and any initial functional impairment resulting from the
      tumor. The addition of systemic chemotherapy to definitive radiation has now been
      demonstrated to produce a significant survival benefit for patients with advanced
      squamous cell head and neck cancer originating in the oropharynx and elsewhere.
      Although there are still specific indications for primary surgical resection, the
      use of chemotherapy and radiation has become a standard of care for the
      management of patients with this disease, with surgery often reserved for salvage
      of those who fail definitive nonoperative treatment. Debate continues as to the
      best tolerated and most successful combination of chemotherapy drugs, radiation
      fractionation schema, and coordination of treatment modalities; however, a
      reproducible survival benefit has been demonstrated only for the concomitant,
      platinum-based treatment schedules. The focus of future investigation must be on
      optimizing these multimodality approaches, minimizing toxicities and functional
      deficits while maximizing treatment success. It is hoped that the addition of the
      newer therapeutic approaches, including epidermal growth factor receptor
      inhibition and gene therapy, may further improve the results of more traditional
      treatment combinations. Continued enrollment of patients in well-designed and
      conducted clinical trials is of paramount importance.

PMID- 12525276
TI  - Organ preservation strategies in the treatment of laryngeal cancer.
AB  - For most patients, a total laryngectomy should not be used as the initial
      treatment for any stage laryngeal tumor. The goal in treating a patient with
      laryngeal cancer must be not only to cure but also to provide the best functional
      outcome for the patient. In the United States, the treatment of laryngeal cancer
      has moved from radical surgery toward a more conservative approach involving
      definitive radiotherapy and chemotherapy, with extirpative surgery held in
      reserve for salvage. In Europe, there has been increasing reliance on limited
      endoscopic cordectomy procedures for early tumors and the use of function
      preserving surgical approaches for more advanced lesions. Careful monitoring of
      the conservatively treated patient is mandatory to allow for early salvage of
      failures to the original therapy. Because of the high costs of hospitalization,
      the direct medical costs attributable to conservative approaches are equal to or
      less than the costs for more radical surgical resections. Even if survivals are
      only equivalent, organ preservation approaches should be the treatment of choice
      for most patients.

PMID- 12525278
TI  - The management of the patient undergoing combined modality therapy for locally
      advanced non-small cell lung cancer.
AB  - Multimodality management of locally advanced non-small cell lung cancer is
      commonplace. Locally advanced disease is defined as patients with stage IIIA,
      IIIB (without pleural effusions), and Pancoast tumors. Improvements in the median
      and landmark survival rates of patients have been accomplished by integration of
      chemotherapy, radiotherapy, and surgery. Although the optimal sequencing and
      number of modalities remains to be established, the safe treatment of patients
      requires cooperation of the specialties (joint clinics and tumor boards). The
      toxicities of chemoradiotherapy are esophagitis, pneumonitis, and
      myelosuppression. These complications are a function of the dose and
      fractionation scheme of radiotherapy and the dose, schedule, and specific
      chemotherapy agents used. The use of modern techniques, including three
      dimensional conformal radiotherapy, limitation of field size, and aggressive
      treatment of symptoms reduces toxicity and the number of treatment breaks, and
      allows delivery of planned therapy in many patients. In appropriate patients,
      surgery may be successful after induction chemotherapy or chemoradiotherapy. In
      addition to exclusion of medically inappropriate patients, patients with
      persistent mediastinal adenopathy after induction therapy are not likely to
      benefit from resection. Therefore, mediastinal sampling must be repeated after
      chemoradiotherapy and before surgery.

PMID- 12525279
TI  - Management of patients with non-small cell lung cancer and poor performance
      status.
AB  - Lung cancer is the leading cause of cancer-related deaths. Non-small cell lung
      cancer (NSCLC) accounts for approximately 86% of patients with lung cancer. The
      two most powerful predictors of long-term outcome in patients with NSCLC are the
      stage and performance status (PS) at diagnosis. Although the cure rates of
      patients with resected stage I and II NSCLC are 50% and 40%, respectively, only
      20% of patients treated with chemotherapy and radiation for locally advanced
      NSCLC are cured of their illness. Patients with metastatic NSCLC do not have
      curative potential with available therapies. Outcome for patients with NSCLC and
      poor PS is dismal. Patients with localized disease and poor PS are treated with
      radiation therapy. Patients with locally advanced NSCLC are treated with
      sequential chemotherapy, followed by radiation therapy. The suggested treatment
      options for patients with metastatic disease and poor PS are single-agent
      chemotherapy or supportive care.

PMID- 12525277
TI  - Oral cancer treatment.
AB  - Oral cancer is the sixth most common cancer in the world, and it continues to
      represent a serious public health problem. Oral cancer is a preventable disease,
      related to behavioral and lifestyle factors, including tobacco and alcohol.
      Prevention and early detection of oral cancer remain the goals of national
      efforts to reduce the impact of this disease on the public. Surgical treatment is
      the mainstay of therapy for patients with oral cancer, particularly in advanced
      stages of cancer. External beam radiation therapy and brachytherapy have been
      used successfully as the primary modality for treating patients with early stage
      oral cancer, and they are the standard of care for use as adjuvant therapy in
      postoperative cases of patients with advanced stage oral cancer. There is an
      emerging trend for the use of chemotherapy in combination with radiation therapy
      and surgery for patients with advanced, recurrent, and metastatic head and neck
      cancer, although evidence is limited regarding survival benefit when used for
      treating patients with oral cavity carcinoma. Any report on the treatment of oral
      cancer is incomplete without consideration of functional and aesthetic outcomes,
      particularly addressing speech, swallowing, masticatory efficiency, and dental
      rehabilitation. Future generations will continue to fight these dreadful diseases
      until scientists and clinicians are provided the opportunities to expand efforts
      to prevent, detect (early), and eradicate oral and other head and neck cancers.

PMID- 12525280
TI  - Limited stage small cell lung cancer: treatment and therapy.
AB  - Chemotherapy remains the key treatment for small cell lung cancer; today, that
      chemotherapy remains cisplatin and etoposide in a variety of acceptable
      schedules. Attempts to use new drugs in extensive disease have not been as
      successful as hoped; however, a recent trial from Japan supports the use of
      irinotecan and cisplatin over the standard cisplatin and etoposide, but these
      facts need to be verified in western countries. For limited disease, the addition
      of thoracic radiotherapy for all patients and prophylactic cranial irradiation
      (PCI) in complete, or near complete, responders have resulted in improved
      survival. The best results occur with early, intensive thoracic radiotherapy
      concurrent with chemotherapy and PCI after completion of systemic and local
      therapy. The use of PCI and thoracic radiotherapy in extensive disease is more
      controversial and less evidence based. PCI and thoracic radiotherapy may be
      considered only in patients who have achieved a "systemic" complete response and
      excellent response in the chest. However, both prospects should be supported if
      there is complete response systemically and near complete response locally. The
      role of surgery is of limited value in the unusual cases of mediastinal negative
      disease, but it is a good treatment for patients with peripheral nodules and
      sufficient pulmonary function to withstand thoracotomy.

PMID- 12525281
TI  - Solitary sites of metastatic disease in non-small cell lung cancer.
AB  - Metastatic (stage IV) non-small cell lung cancer is a lethal disease, with few
      patients surviving longer than 5 years. Surgery is not an option, and adjuvant
      therapy regimens (platinum-based chemotherapy, radiation therapy, and supportive
      care) have been structured around palliation and maximizing the quality of life
      for patients. However, patients with solitary foci of metastatic disease
      represent a subgroup with a better prognosis. Studies have indicated that
      surgical resection may enhance the survival rate of patients in this setting.
      Patients who have resectable primary tumors and a solitary site of metastasis,
      based on a thorough metastatic work-up, benefit from surgical resection (primary
      tumor and solitary metastasis). The role of adjuvant chemotherapy and radiation
      depends on the individual and patient setting. There have been several case
      series indicating an improvement in the long-term (5-year) survival rates of
      patients after surgical resection of solitary metastases of the brain, adrenal
      gland, and other sites. Prospective trials will be required to determine the
      magnitude of benefit of surgical resection for patients and the role of
      multimodality therapy. The standard of care for patients with solitary metastases
      in non-small cell lung cancer should include consideration of surgical resection
      and ablation. Favorable criteria include control of the primary tumor, a negative
      metastatic survey, good performance status, and a significant metachronous
      interval.

PMID- 12525282
TI  - Early stage medically inoperable non-small cell lung cancer.
AB  - A nihilistic approach to the treatment of patients with medically inoperable,
      early stage non-small cell lung cancer (NSCLC) is not warranted. Despite the
      frequency of comorbid medical illness in patients with medically inoperable
      NSCLC, lung cancer progression is the major cause of morbidity and death.
      Although expectations for cure are reduced compared to good-risk patients (eg,
      adequate pulmonary reserve), modest long-term survival rates of patients have
      been reported, after definitive therapy. A comparison of radiotherapy and limited
      resection is difficult because of the lack of randomized data and the selection
      bias inherent in retrospective reports. For example, patients treated with
      surgery have peripheral lesions, undergoing rigorous staging compared to patients
      treated with radiotherapy. In a multidisciplinary thoracic program, patients are
      counseled on the options of sublobar resection and conformal radiotherapy. The
      efficacy of adjuvant radiotherapy, after limited resection, in reducing local
      recurrence in patients with medically inoperable NSCLC is unclear. However,
      adjuvant radiotherapy may be considered if a postoperative target volume can be
      defined, particularly if resection margins are narrow. Considering the benefit of
      chemoradiotherapy for patients with locally advanced disease, combination therapy
      is administered to patients with good performance status and large (eg, > 4 cm)
      primary lesions, although combined therapy may increase the potential for
      pulmonary toxicity in patients with baseline pulmonary dysfunction. Prospective
      data are becoming available to define the value of treatment alternatives for
      patients with medically inoperable NSCLC. The Cancer and Leukemia Group B
      completed a phase II study of thoracoscopic wedge resection and postoperative
      radiotherapy, whereas a phase I trial of dose-intensive accelerated conformal
      radiotherapy is ongoing. Trials involving systemic therapy for patients with
      medically inoperable NSCLC should be developed.

PMID- 12525283
TI  - Treatment options for brain metastases in patients with non-small cell lung
      cancer.
AB  - Brain metastases are a common complication for patients with non-small cell lung
      cancer and a significant cause of morbidity and mortality. In the past, treatment
      of brain metastases and lung cancer focused on symptom palliation with whole
      brain radiotherapy (WBRT) and steroids because of the grim outlook for patients.
      However, recent advances in technology and surgical techniques have created more
      options for the management of brain metastases, which include surgery,
      irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive
      approaches have resulted in an improvement of neurologic outcomes and survival
      rates of patients with non-small cell lung cancer. Central nervous system (CNS)
      metastases can be divided into three groups: solitary CNS metastases with
      controlled or controllable primary disease, oligometastatic disease (fewer than
      three metastases), and multiple metastases. For patients with solitary CNS
      metastases, long-term survival is possible. A radical treatment approach
      involving surgical resection or radiosurgery, followed by WBRT, is recommended.
      For patients with oligometastatic disease, surgical resection or radiosurgery is
      considered in selected cases and WBRT is indicated. For patients with multiple
      metastases, WBRT is recommended. For patients with oligometastatic disease and
      patients with multiple metastases, recent evidence indicates that systemically
      effective chemotherapy may produce responses and can be instituted safely before
      radiotherapy. The treatment timing of chemotherapy and radiotherapy should be
      individualized.

PMID- 12525284
TI  - Antibiotic Prophylaxis of Endocarditis: What Is Accomplished and at What Cost?

PMID- 12525285
TI  - The Role of Antibiotics in Acute Exacerbations of Chronic Obstructive Pulmonary
      Disease.
AB  - Our understanding of the pathogenesis and consequences of acute exacerbations of
      chronic obstructive pulmonary disease (COPD) has increased considerably in the
      past decade. Several new lines of evidence support bacterial causation of about
      half the exacerbations. Contrary to previous data, recent studies with improved
      methodology have demonstrated that exacerbations do contribute to the loss of
      lung function in COPD. Another interesting new observation is that colonization
      by bacterial pathogens may not be innocuous, and in fact may lead to airway
      inflammation and contribute to pathogenesis of COPD. Evidence that bacteria cause
      exacerbations, that exacerbations contribute to loss of lung function, and that
      chronic colonization by bacteria may be harmful, has emphasized the potential
      importance of appropriate antibiotics in the treatment of exacerbations. An
      unfortunate paucity of data does not allow evidence-based recommendations to be
      made for optimal choice of antibiotics for exacerbations of COPD. Emerging data
      that antibiotics differ in unconventional measures of efficacy such as time to
      next exacerbation, improvement in health-related quality of life, and
      bacteriologic eradication will help us make concrete recommendations in the
      future.

PMID- 12525286
TI  - What's New in Antifungals?
AB  - The incidence of fungal infections is steadily rising. Until recently, clinicians
      have been limited in the number of effective antifungal agents at their disposal.
      Our traditional antifungal agents have either been hampered by troublesome side
      effects or a limited spectrum of activity. Due to the rising demand for better
      antifungal agents there are more agents in development than ever. Voriconazole
      and caspofungin are the most recent agents approved for use, offer a broad
      spectrum of activity, and are generally well tolerated. Several other novel
      agents are moving into clinical trials. A better understanding of these novel
      agents is critical for clinicians to effectively treat emerging fungal pathogens.

PMID- 12525287
TI  - Therapeutic Options for Herpes Simplex Infections.
AB  - Herpes simplex viruses are responsible for a number of disease states in infected
      individuals. Capable of establishing latent infection, herpes simplex can
      reactivate, causing pain, discomfort, and psychosocial consequences. Because no
      cure is available, treatment modalities for herpes simplex infection are
      required, from both personal and public health standpoints. To date, therapy has
      centered around the use of antiviral drugs to control infection and suppress
      recurrences. To expand the scope of available treatments, efforts have focused on
      the development of vaccines against herpes simplex virus and new agents such as
      immune response modifiers. Recent data suggest that these new agents are
      promising in their therapeutic potential.

PMID- 12525289
TI  - Development status of miltefosine as first oral drug in visceral and cutaneous
      leishmaniasis.

PMID- 12525288
TI  - The Treatment of Severe Group A Streptococcal Infections.
AB  - Group A streptococci can cause a variety of diseases ranging from uncomplicated
      superficial infections to severe systemic infections associated with high
      morbidity and mortality. Since the late 1980s a drastic resurgence of highly
      aggressive invasive streptococcal infections, including streptococcal toxic shock
      syndrome and necrotizing fasciitis, have been noted worldwide. This has prompted
      intense research in the field and important new information has been gained
      regarding the pathogenesis and treatment of life-threatening invasive group A
      streptococcal infections. Exotoxins with superantigenic activities have been
      identified as central mediators of the systemic effects seen in streptococcal
      toxic shock syndrome. Novel therapeutic strategies include agents that can
      inhibit these superantigens, and one promising candidate is intravenous
      polyspecific immunoglobulin that contains neutralizing antibodies against a wide
      spectrum of streptococcal superantigens. Intravenous immunoglobulin adjunctive
      therapy was shown in a case-control study to reduce mortality in patients with
      streptococcal toxic shock syndrome.

PMID- 12525290
TI  - Special Challenges in the Prevention and Treatment of Malaria in Children.
AB  - Malaria is a devastating disease, inflicting epidemic morbidity and mortality
      with an estimated 500 million cases and 2.5 million deaths annually. Children
      suffer the most severe morbidity; one child dies of malaria every 30 seconds,
      accounting for over 1 million of the deaths annually. There continues to be a
      tremendous increase in human migration and travel between malaria endemic and
      nonendemic areas, with approximately 20% of imported malaria cases to Europe and
      the United States occurring in children. Although many recent advances in the
      prevention, diagnosis, and treatment of malaria have been made, the emergence of
      drug resistance and changes in the disease's epidemiology present new challenges.
      This article discusses the special considerations encountered in the prevention
      and treatment of malaria in children.

PMID- 12525291
TI  - Babesiosis: An Update on Epidemiology and Treatment.
AB  - Babesiosis is caused by a tick-borne hemoparasite that, like malaria, can cause
      fever, hemolysis, and anemia. Typically self-limited, in the asplenic,
      immunocompromised, or elderly, disease can be severe or deadly. US cases have
      been primarily due to Babesia microti; WA-1, which may be related to Babesia
      gibsoni; and MO-1, related to Babesia divergens. European infections are usually
      due to B. divergens. North American cases are treated either with quinine and
      clindamycin or with atovaquone and azithromycin. The latter regimen appears less
      toxic.

PMID- 12525292
TI  - Changing Epidemiology and Approaches to Therapy for Chagas Disease.
AB  - Impressive progress has been made in reducing the incidence of Chagas disease, or
      American trypanosomiasis, in many countries in which the illness is endemic. This
      has been achieved through expanded blood screening programs and low-technology
      vector control. Despite the progress made in reducing the number of new cases,
      the burden of disability and mortality in the endemic countries is enormous and
      will continue to be so for many years since a substantial portion of the 16 to 18
      million persons already infected will develop chronic symptomatic Chagas disease.
      Unfortunately, no progress has been made in developing new drugs for Trypanosoma
      cruzi infection, and nifurtimox and benznidazole, both of which lack efficacy and
      often cause severe side effects, remain the only options for treatment.

PMID- 12525293
TI  - Emerging Causes of Traveler's Diarrhea: Cryptosporidium, Cyclospora, Isospora,
      and Microsporidia.
AB  - Travel is a risk factor for acquiring infection with a spore-forming protozoa:
      Cryptosopridium, Cyclospora, Microsporidia, and Isospora. Certain travel
      destinations have a high disease burden and intense exposure. Patients present
      with persistent diarrhea and a history of recent travel to a developing country
      in the tropics. Very mild infections may be underdiagnosed and may cause typical
      traveler's diarrhea. In a patient with a history of travel and persistent
      diarrhea unresponsive to the usual antibiotic and antidiarrhea treatment, stool
      studies for all four of these protozoa infections should be performed. If immune
      status is normal and the disease is mild, symptomatic therapy may suffice.
      Effective treatment is available for Cyclospora, Microsporidia, and Isospora.

PMID- 12525294
TI  - HIV-1 Fitness and Replication Capacity: What Are They and Can They Help in
      Patient Management?
AB  - The natural history of HIV-1 infection is characterized by persistent viremia,
      progressive CD4 lymphopenia, and profound immune suppression resulting in
      opportunistic infections, neoplasms, and death. Introduction of combination
      antiretroviral therapy has been effective in suppressing HIV-1 replication,
      reversing immunodeficiency to a degree, reducing HIV-1-associated complications,
      and thereby prolonging life. One of the most vexing challenges of prolonged
      antiretroviral therapy is the development of drug resistance. Antiretroviral
      therapies fail in a substantial number of cases, often with emergence of HIV-1
      variants encoding mutations that confer potent drug resistance to individual
      agents or entire drug classes. Resistance testing methods have been introduced to
      evaluate drug resistance, and several studies have reported clinical benefits of
      genotyping and phenotyping assays in clinical decision-making. However, the
      genetic variability of HIV-1 to develop resistance exceeds the antiretroviral
      armamentarium, and the number of patients with drug experience and resistance to
      all classes of antiretrovirals continues to grow. From a clinical standpoint, it
      would be useful to have a more comprehensive grasp of pathogenic determinants of
      HIV-1 in all patients. One proposed in vitro correlate of HIV-1 pathogenic
      potential is the replication capacity of HIV-1. New techniques to assess HIV-1
      replication potential are in development, with a commercial assay now available
      to analyze clinical samples. In this review we explore the experimental basis for
      replication capacity measurements and potential clinical applications of this
      methodology.

PMID- 12525296
TI  - [Intravenous tissue-type plasminogen activator for the treatment of acute
      cerebral ischemia].
AB  - BACKGROUND AND OBJECTIVE: Whether the risk of symptomatic hemorrhagic
      transformation (SHT) of cerebral infarction associated with the use of tissue
      plasminogen activator (t-PA) is higher in clinical practice than in clinical
      trials is unknown. The aim of this study was to analyze the safety profile and
      clinical outcome of patients with acute cerebral ischemia who received open
      treatment with t-PA in Spanish hospitals. PATIENTS AND METHOD: This prospective
      and observational study included 155 consecutive patients with an ischemic stroke
      treated within 3 hours from the onset of symptoms, or within 6 hours in the
      absence of early signs of large cerebral infarction on CT. Intravenous t-PA was
      administered at 0.9 mg/kg (10% as bolus) during a 60 minutes infusion.
      Neurological worsening within 24-36 hours was evaluated by the NIH stroke scale
      (NIHSS). Primary safety and outcome variables were SHT on CT performed at 24-36
      hours, mortality and independence at 90 days. Patients were treated by
      neurologists with expertise in acute stroke, and stroke monitoring was performed
      in acute stroke units. RESULTS: Baseline median NIHSS was 16, and mean time from
      stroke onset to treatment was 163 minutes. SHT was found in 12 patients (7.7%;
      95% CI, 4.0-13.1), and it was fatal in 7 (4.5%, 95% CI, 1.8-9.1). Overall
      mortality at 90 days was 16.8% (95% CI, 11.2-23.6). At 24 hours, 48% (95% CI,
      39.7-55.9) of patients had improved >= 4 points in the NIHSS, and 29% (95 % CI,
      22.0-36.8) showed a >= 10 points improvement or total recovery. At 3 months, 56%
      (95% CI, 47.9-64.1) of patients were independent. CONCLUSIONS: In Spanish
      hospitals with stroke units or stroke teams, the use in the clinical practice of
      intravenous t-PA by experienced neurologists is safe, and it is associated with a
      favourable outcome similar to that observed in clinical trials.

PMID- 12525295
TI  - Update on Kaposi's Sarcoma: A Gammaherpesvirus- induced Malignancy.
AB  - Since the beginning of the AIDS epidemic, Kaposi's sarcoma (KS) has been one of
      the most visible manifestations of this disease and one of the most distressing
      for affected patients. The discovery in 1994 of a new gammaherpesvirus, called
      Kaposi's sarcoma-associated herpesvirus, has led to increased understanding of
      the pathogenesis of this disease and the potential for new specific therapy. In
      addition, the development of highly active antiretroviral therapy has had a
      substantial impact on the incidence of KS in countries where it is available and
      on the course of established disease. Finally, recent advances in our
      understanding of angiogenesis have the potential of leading to new KS therapies.
      In this article we review some of the recent advances in the epidemiology and
      pathogenesis of KS, review the current treatment of this disease, and discuss
      several therapeutic approaches that are now under development.

PMID- 12525298
TI  - [Transmission of hepatitis C virus in pregnant women].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to determine the prevalence of hepatitis C
      virus infection in pregnant women from Asturias as well as the vertical
      transmission rate. PATIENTS AND METHOD: This was a prospective study of
      consecutive pregnant women from the 5th Health Area of Principado de Asturias
      (Northern Spain). We determined the prevalence of hepatitis C virus infection in
      the first trimester of pregnancy and the rate of mother-to-child transmission.
      Time period was August 1997-December 1998. Children were followed from birth to
      18-24 months of age. Methods included anti-HVC, PCR-RNA-HVC, genotype and viral
      load at delivery of all positive women; and anti-HVC and PCR-RNA-HVC at birth, 3,
      6, 12 and 18 months of age of their children. RESULTS: Out of 2442 consecutive
      pregnant women, 30 were anti-HVC positive (prevalence: 1.23% of pregnancies and
      1.20% of women); 24 of them were PCR-RNA-HVC positive. There were 30 anti-HVC
      positive children. All but one lost their antibodies (vertical transmission rate
      3.3%). CONCLUSIONS: The prevalence of hepatitis C virus infection was 1.20% of
      women from our Health Area. Vertical transmission rate was 3.3% among HVC
      infected, non-selected mothers.

PMID- 12525297
TI  - [Biological differences on onset among type 1A diabetics in relation to HLA-DQ
      genetic markers].
AB  - BACKGROUND AND OBJECTIVE: The hypothesis that diabetes mellitus presentation
      partially depends on the genetic characteristics of the patient has been
      proposed. Up to date this kind of studies have been made by serology, so there
      are no data about the role played by DQ haplotypes in the presentation and
      clinical importance of DM1. This fact is analysed in the present study. PATIENTS
      AND METHOD: We studied DQ haplotypes (molecular biology) in 86 patients affected
      by DM1. Their relationship with several parameters found on illness debut, such
      as age, sex, C peptid and clinical importance are analysed. RESULTS: 89% of the
      patients showed a DQ that increases the risk of diabetes. Average age on onset
      was 16 years and the median age 9 years. No differences in relation to sex were
      observed. DQA1*0501, 0301/DQB1*0201, 0302 heterocygotes show an earlier onset (9
      years, opposite to 17 in the rest) and the youngest (smaller than 16 years) they
      have to the onset a smaller pancreatic reservation (peptid C of 0.37 ng/dl in
      front of 1.4 of those bigger than this age). CONCLUSIONS: DQA1*0501,
      0301/DQB1*0201 heterocygocity increases the probability of an earlier and more
      aggressive debut of the illness, being related this characteristic younger debut
      to a smaller pancreatic reservation.

PMID- 12525299
TI  - [Smoking in Spain, 1945-1995. A retrospective analysis based on the Spanish
      National Health Interview Surveys].
AB  - BACKGROUND AND OBJECTIVE: To analyse trends in cigarette consumption in Spain
      between 1945 and 1995. MATERIAL AND METHODS: Prevalence rates of daily cigarette
      smoking were derived from the individual information collected in the Spanish
      National Health Interview Surveys (1993, 1995 and 1997) for the period 1945-1995.
      RESULTS: In males, the prevalence rate in 1945 was 42.4% (95% confidence interval
      [CI], 40,1-44,7%), increased till 59.1% in 1975 (95% CI, 58,0-60,2%), levelled
      off during the decade 1975-1985, and decreased till 48.9% in 1995 (95% CI, 48,1
      49,7%). In females, the prevalence rate of cigarette smoking was less than 5%
      till the 1970s, and it begun to steadily increase till the end of the study
      period (22,5%; 95% CI, 21,9-23,1%). CONCLUSIONS: This analysis shows the
      different dynamics of the smoking epidemic among men and women in Spain.

PMID- 12525300
TI  - [Unblocking arteries to save brains: thrombolysis in patients with stroke].

PMID- 12525301
TI  - [Thoughts on biomedical research in Spain].

PMID- 12525302
TI  - [Advances in the medical and minimally invasive treatment of chronic ischemia of
      lower limbs].

PMID- 12525303
TI  - [Androgens in menopausal women].

PMID- 12525304
TI  - [Diagnosis of human taeniasis by multiplex-PCR].

PMID- 12525305
TI  - [Bronchiolitis obliterans with organizing pneumonia and primary biliary
      cirrhosis].

PMID- 12525306
TI  - [Prevalence of hormone replacement therapy].

PMID- 12525307
TI  - [Recurrence of sarcoidosis after liver transplantation].

PMID- 12525308
TI  - [Clinical and biological differences between infiltrating ductal carcinomas of
      the breast in women over 70 years-old and those aged 60-70].
AB  - BACKGROUND: There is discrepancy in the literature regarding the behavior of
      breast cancer in elderly women. For this reason we decided to study the possible
      clinical and biological differences of infiltrative ductal breast carcinoma
      between women over 70 years and those aged between 60 and 70 years. PATIENTS AND
      METHOD: The study group included 181 women with infiltrative ductal carcinomas
      (IDCs) who were referred from a breast clinic (BC) and a breast cancer screening
      campaign (BCS). 67 of them were older than 70 and 114 were between 60 and 70
      years old. Estrogen receptors (ER), progesterone receptors (PR), pS2 and
      cathepsin D cytosolic levels were determined, as well as levels of epidermal
      growth factor receptor (EGFR) in cell surfaces. Likewise, size, axillary lymph
      node involvement, distant metastasis, histological grade, ploidy and cellular S
      phase fraction were also considered as variables of the study. RESULTS: IDCs in
      women older than 70 had greater size (p<0.001), global S-phase (p = 0.009) and
      number of axillary lymph nodes involved (p = 0.002). Likewise, these tumors
      showed more frequently distant metastasis (p = 0.001) and S-phase values >14% (p
      = 0.093). However, when we considered only women referred from BCS, no
      differences in the parameters studied between women older than 70 and those aged
      between 60 and 70 years were observed. When only patients coming from BC were
      considered, women older than 70 had a greater number of axillary lymph nodes
      involved (p= 0.027). Patients older than 70 years from BC showed greater size (p=
      0.054) and more common distant metastasis (p= 0.075) than those from BCS. Also,
      patients between 60 and 70 referred from BC had tumors with greater size (p
      <0.001), nodal involvement (p= 0.022), number of lymph nodes involved (p= 0.022)
      and distant metastasis (p= 0.048) than those from BCS with the same age.
      CONCLUSIONS: Our results suggest that IDCs in women older than 70 years show
      clinical and biological features associated with a worse behaviour. However, this
      is only observed in women referred from BC but not in those coming from BCS. For
      this reason, the patient's referral site seems to be essential for the observed
      clinical and biological differences of breast carcinomas in the elderly.

PMID- 12525309
TI  - [Micronutrients in HIV-infection and the relationship with the inflammatory
      response].
AB  - BACKGROUND: Our aim was to measure the plasma concentrations of various vitamins
      and micronutrients involved in the immune response and antioxidant systems of an
      HIV+ population and to determine how they are related to the inflammatory
      response. PATIENTS AND METHOD: We studied 86 subjects with known HIV-infection
      who were divided into three groups (asymptomatic HIV+; AIDS without opportunistic
      infection; and AIDS with active opportunistic infection) which were compared with
      a control group. Serum concentrations of vitamin A, vitamin E, copper and zinc
      were measured, as well as several inflammatory parameters. Absorption tests for
      fat and sugar were performed in all patients. RESULTS: Serum vitamin A and E
      levels were below the reference range in 36.4% and 14.3% patients, respectively,
      but not in controls subjects. The prevalence of vitamin A deficiency increased
      with the severity of the disease. Fewer patients than controls had values below
      the reference range regarding serum copper. AIDS patients with active
      opportunistic infection showed significantly lower serum concentrations of
      vitamin A (p < 0.001) and significantly higher serum concentrations of copper (p
      < 0.0001). Both serum concentrations of vitamin A and copper were correlated with
      various inflammatory parameters. CONCLUSIONS: Micronutrient deficiencies are
      prevalent in HIV-infected patients including asymptomatic patients. Vitamin A and
      copper were significantly correlated with inflammatory parameters, suggesting
      that their serum concentrations have more to do with the inflammatory response
      than with the nutritional status.

PMID- 12525311
TI  - [Acquired hemophilia].

PMID- 12525310
TI  - [Fetal microchimerism in patients with primary biliary cirrhosis].
AB  - BACKGROUND: Fetal microchimerism (FM) has been implicated in the pathogenesis of
      primary biliary cirrhosis (PBC). The aim of the study was to investigate the
      presence of FM in PBC patients. PATIENTS AND METHOD: FM was studied in 28 women,
      14 with PBC and 14 healthy controls.DNA was extracted from peripheral blood
      cells, and a PCR analysis to detect a specific Y-chromosome sequence was
      performed. Specificity was confirmed by Southern-blot analysis. RESULTS: The Y
      chromosome sequence was amplified from peripheral-blood cell DNA in only one PBC
      patient and in none of the controls. CONCLUSIONS: FM does not seem to play a
      major role in patients with PBC.

PMID- 12525313
TI  - [Cardiac resynchronisation therapy in congestive heart failure. Current concept,
      results and prospects].

PMID- 12525312
TI  - [Mountain medicine in 2002 (United Nations' International Year of Mountains).
      Past, present and future].

PMID- 12525314
TI  - [Anticardiolipin antibodies anti-beta2-glycoprotein and other autoantibodies in
      chronic hepatitis C according to their genotype].

PMID- 12525315
TI  - [Reversible posterior encefalopathy syndrome during induction chemoterapy for
      acute lymphoblastic leukemia].

PMID- 12525316
TI  - [Role of the magnetic resonance in the diagnosis and follow up of eosinophilic
      fascitis].

PMID- 12525317
TI  - [Seizures as late manifestation of alprazolam withdrawal syndrome].

PMID- 12525318
TI  - [Uterine leiomyosarcoma as a cause of fever of unknown origin].

PMID- 12525319
TI  - [Hematomyelia as late side effect of radiation].

PMID- 12525320
TI  - [Expression and clinical significance of collagenase-3 (MMP-13) in gastric
      cancer].
AB  - BACKGROUND: MMP-13 (collagenase-3) is a metalloproteinase with potent degradative
      activity against a variety of elements of the extracellular matrix. Its
      expression has been described in some human carcinomas, where it seems to play a
      role in tumor progression and metastasis. The objective of this study was to
      investigate the expression and clinical significance of MMP-13 in gastric
      carcinomas. PATIENTS AND METHOD: MMP-13 expression was analyzed by
      immunohistochemistry in resected specimens from 44 patients with gastric
      adenocarcinoma. The mean ( standard error) follow-up period was 21.4 3.2 months.
      RESULTS: A total of 14 gastric carcinomas (31.8%) showed positive immunostaining
      for MMP-13. The percentage of MMP-13-positive tumors was significantly (p =
      0.009) higher in stage IV carcinomas (69.2%) than in lower stages (I: 22.2%; II:
      12.5%; and III: 14.3%), as well as in nonresectable tumors (R1 and R2) (61.5%)
      than in resectable carcinomas (R0) (19.4%) (p = 0.017). Likewise, MMP-13 tumor
      expression was significantly associated with shortened overall survival in both
      the entire group of patients (p = 0.0006) and in the subgroup of patients with
      resectable tumors (p = 0.018). CONCLUSIONS: Our results suggest that, in patients
      harboring gastric adenocarcinoma, MMP-13 tumor expression is associated with
      higher tumor aggressiveness and a poor prognosis.

PMID- 12525321
TI  - [Dynamic ultrasonography in the diagnosis of gallbladder dysfunction: reliability
      of a simple method with easy clinical application].
AB  - AIMS: Although the results of dynamic ultrasonography (DUS) are similar to those
      of dynamic cholescintigraphy (DCS) in the study of gallbladder function, the
      methodology required for this technique is laborious and sometimes complex. The
      aim of this study was to investigate the reliability of a simple method of DUS to
      evaluate gallbladder function using DCS as a reference. PATIENTS AND METHODS:
      Gallbladder function was studied using DUS and DCS in 80 consecutive patients
      with clinical findings compatible with gallbladder dysfunction. For DUS the
      ellipsoid method was used with measurement of three gallbladder diameters
      (transversal, longitudinal and anteroposterior) in basal conditions and after
      applying a cholecystokinetic stimulus (meal test); gallbladder emptying of less
      than 50% was considered abnormal. In DCS intravenous cholecystokinin (CCK) (0.40
      IDU/kg in 20 minutes) was used as stimulus and an ejection fraction < or = 40%
      was considered abnormal. RESULTS: In 15 patients (19%; 95% CI, 11-29%) abnormal
      gallbladder response was found using DUS. The ejection fraction in the entire
      group of patients studied was 48 26.2%. Ejection fraction was abnormal in 41
      patients (51%; 95% IC, 40-63%) with a value of 25 8.5% and was normal in 39
      patients (49%; 95% IC, 40-63%) with a value of 71.5 14.5%. The correlation
      coefficient between the values of gallbladder emptying calculated with DUS and
      the ejection fraction obtained with DCS was 0.199 (p = 0.079). When patients were
      divided according to gallbladder emptying measured by DUS and the ejection
      fraction obtained with DCS the concordance was very low (k = 0.065; EE = 0.085).
      CONCLUSIONS: DUS performed using a simple technique lacks diagnostic value in
      gallbladder dysfunction when DCS is taken as a reference test

PMID- 12525322
TI  - [Endoscopic treatment of pancreatitis and its complications].
AB  - OBJECTIVES: To study the long- and short-term safety and efficacy of endoscopic
      treatment of pancreatitis and its complications in our environment. PATIENTS AND
      METHODS: We performed a retrospective analysis of 43 patients with chronic
      pancreatitis, acute pancreatitis complicated with pseudocyst, and pancreatic
      fistula diagnosed by endoscopic retrograde cholangiopancreatography who were
      suitable for endoscopic treatment. RESULTS: Endoscopic treatment was attempted in
      35 patients. The indication for treatment was pain in 17 patients (48.5%),
      jaundice in 7 (20%), pseudocyst in 10 (28.5%) and suspected external fistula in 1
      (3%). The technique was successfully performed in 28 (80%). Of the patients with
      pain, pancreatic prosthesis was inserted in 13 and extracorporeal lithotripsy was
      applied in 6. Sixty-five percent of the patients improved. Of the 7 patients with
      jaundice, all had secondary stenosis of the biliary tract. Treatment was applied
      in 2, who showed partial improvement. Of the 15 patients with pseudocyst,
      endoscopic treatment was indicated in 10; the technique was successfully
      performed in 8 and complete resolution was achieved in 7 (87.5%). The patient
      with external fistula was treated with transpapillary prosthesis and complete
      resolution of disruption of Wirsung's duct was achieved. Overall improvement in
      successfully treated patients was: complete in 19 (68%), partial in 3 (18%), no
      improvement in 4 (14%) and 2 patients were lost to treatment. There were 4 short
      term complications. There were 4 deaths and one was related to the technique.
      CONCLUSIONS: Endoscopic treatment of chronic pain in chronic pancreatitis,
      pseudocysts and fistulas was effective in our environment with a low rate of
      complications.

PMID- 12525323
TI  - [Opportunistic infections in patients with inflammatory bowel disease undergoing
      immunosuppressive therapy].
AB  - Immunosuppressive agents (azathioprine, methotrexate) are increasingly being used
      in the treatment of inflammatory bowel disease. The use of immunosuppressive
      agents is associated with a greater risk of opportunistic infections, the most
      frequent of which are those caused by cytomegalovirus and varicella zoster virus.
      We present four cases of opportunistic infections due to Herpesviruses in
      patients undergoing immunosuppressive treatment with azathioprine for Crohn's
      disease. We also review the literature published on this topic. Two patients
      presented cutaneous varicella complicated by pneumonia and esophagitis
      respectively, one patient had cutaneous herpes zoster and the other had fatal
      pneumonia possibly caused by the Herpesvirus. In the first three the clinical
      course of the infection was favorable after withdrawing immunosuppressant
      treatment and initiating treatment with aziclovir. In patients Crohn's disease
      azathioprine treatment increases the risk of opportunistic infection by
      Herpesvirus. However, in the absence of other factors that increase
      immunosuppression, these infections usually have a benign course with specific
      antiviral therapy.

PMID- 12525324
TI  - [Rectosigmoid endometriosis with lymph node involvement].
AB  - Endometriosis mainly affects women of a fertile age and is usually located in the
      pelvis. Extrapelvic involvement is less frequent. We present the case of a female
      patient with endometriosis of the rectosigmoid and mesenteric lymph nodes, which
      is an extremely rare finding. Although the most widely accepted theory of the
      pathogenesis of this disease postulates retrograde menstruation through the
      Fallopian tubes with subsequent implantation in the peritoneum, these findings
      support lymphatic dissemination of endometrial cells as a theory of pathogenesis
      in cases of extrapelvic involvement.

PMID- 12525325
TI  - [Cytomegalovirus hepatitis and ductopenia in a heart transplant recipient].

PMID- 12525326
TI  - [Consensus guideline on tuberculosis and treatment of inflammatory bowel disease
      with infliximab. Spanish Working Group on Crohn Disease and Ulcerative Colitis].

PMID- 12525327
TI  - [Tuberculosis and the digestive tract].

PMID- 12525328
TI  - [Wilson's disease: physiopathological, clinical and therapeutic considerations].

PMID- 12525329
TI  - [Cholangitis and pulmonary metastases as the first manifestation of ampulloma].

PMID- 12525330
TI  - [Invasive cancer of the cervix in a patient undergoing chronic treatment with 6
      mercaptopurine for Crohns disease].

PMID- 12525331
TI  - [Rupture of the Achilles' tendon secondary to levofloxacin].

PMID- 12525332
TI  - [Treatment of steroid-refractory ulcerative colitis with infliximab].

PMID- 12525333
TI  - [The new programme for Family and Community Medicine].

PMID- 12525334
TI  - [Effectiveness of acupuncture in the treatment of pain from osteoarthritis of the
      knee].
AB  - AIM: To determine the effectiveness of acupuncture in controlling pain from
      arthritis of the knee. DESIGN: Systematic review. DATA SOURCES: MedLine, the
      Cochrane Library. STUDY SELECTION: Of the 9 studies located, only 4 met the
      inclusion criteria. All were controlled, randomized clinical trials that studied
      the effect of acupuncture only in the knee joint. DATA EXTRACTION: Primary
      outcome variables were intensity of pain, overall measure (general improvement,
      proportion of patients who recovered, subjective improvement in symptoms) and
      functional status. As secondary outcome measures we used objective physiological
      measures (range of knee movement, muscle strength, time needed to walk a certain
      distance, time needed to climb a certain number of stairs), general health
      status, and other information such as medication needed and side effects.
      RESULTS: There was moderately strong evidence that acupuncture was more effective
      in treating knee joint pain than no treatment. The difference can be explained by
      its marked placebo effect. CONCLUSIONS: There is currently insufficient evidence
      to recommend acupuncture as a treatment for pain from osteoarthritis of the knee.
      Additional, better designed studies are needed to determine the actual role of
      acupuncture in this disease.

PMID- 12525336
TI  - [Impact of primary care on hospitalization of type 2 diabetics with equal
      conditions of health insurance].
AB  - OBJECTIVE: To determine the impact of primary care on hospitalization of type 2
      diabetics with equal conditions of health insurance. DESIGN: A case-control
      study. Case = diabetic hospitalized by a disease related condition. Control =
      diabetic without hospitalization during the last 12 months. SETTING: Urban
      primary care centers. PARTICIPANTS: Cases were consecutively selected from four
      out of five urban hospitals (n=123). Controls were chosen at random from primary
      care units matched by primary care source (n=135). Women with gestational
      diabetes were excluded as well as individuals with missing medical charts
      (approximately 15%). MEASUREMENTS: A primary care index was constructed with
      process and outcome indicators recommended by the American Medical Association,
      the Joint Commission on Accreditation of Healthcare Organizations, the National
      Committee for Quality Assurance, the American Diabetes Association and the
      Official Mexican Standards. Compliance to less than 60% of recommendations was
      considered unsatisfactory primary care. RESULTS: The following were
      hospitalization risk factors: less than 2 visits to family physician during the
      last year (OR adjusted, 16,2; 95% CI, 1,5-174,2), glucose level (OR adjusted,
      1,006; 95% CI, 1,002-1,010) and cognitive level (OR adjusted, 0,98; 95% CI, 0,96
      0,99), in addition to exercising and year of diagnosis. Sixty-five percent of
      cases observed unsatisfactory primary care compared with 49,1% of controls
      (P=0,03). Unsatisfactory primary care increased 2,5 times the risk of
      hospitalization (95% CI, 1,2-5,0) (pseudo R2=0,279; P<0,001). CONCLUSIONS:
      Primary care is a potential factor for reducing hospitalization of type 2
      diabetics. Effective primary care programs would contribute to a better disease
      control and less unnecessary hospitalizations.

PMID- 12525337
TI  - [Survey on the needs expressed by primary care doctors for continuing education
      in drug therapy].
AB  - OBJECTIVE: To describe the aspects of continuing education in pharmacological
      therapeutics considered as most relevant by the primary health care physicians.
      DESIGN: Observational study.Setting. Physicians filled-up the questionnaires
      during 45 minutes at their primary health care centres. PARTICIPANTS: Primary
      health care physicians involved in the Fundation Institut Catala de Farmacologia
      continuing education activities since 1997 were selected. MAIN MEASUREMENTS: A
      specific questionnaire was designed to collect the physicians' opinion on
      different topics regarding continuing education in pharmacological therapeutics.
      RESULTS: 180 physicians from 21 primary health care centres answered the
      questionnaire. 68% of the responding physicians considered that continuing
      education has to be useful to improve routine clinical practice. Regular seminars
      and methods stimulating active participation administered by primary health care
      professionels are preferred. Continuing education in pharmacological therapeutics
      should be focused to health problems rather than being drug-oriented. They
      referred being more interested in drug selection issues and in the role of new
      drug in comparison with the existing alternatives rather than in regulation and
      drug consumption issues. 66,3% of the responding physicians considered that
      continuing education in pharmacological therapeutics should be compulsory. Public
      health authorities and primary health care physicians should share the
      responsibility in setting-up continuing education in pharmacological therapeutics
      programs, according to the opinion of almost 70% of the physicians. CONCLUSIONS:
      Primary health care physicians are interested in continuing education in
      pharmacological therapeutics as far as it is practical and useful to solve
      problems of their routine clinical practice.

PMID- 12525338
TI  - [Construct validity of FACES III questionnaire in Spanish (Mexico)].
AB  - OBJECTIVE: To determine the construct validity of FACES III in spanish (Mexico).
      DESIGN: Cross-sectional study, descriptive, confirmatory. SETTING: Mexico City,
      South of Federal District, Tlalpan area, divided into geo- statistical zones of a
      primary care unit. PATIENTS AND OTHER PARTICIPANTS: A random sample of 270
      families selected in their dwellings with proportional coverage based on 17 895
      dwellings of the influence area. Measurements and main results. Domicile survey
      applying FACES III (Family Adaptability and Cohesion Evaluation Scales) in
      spanish, Mexico. Twelve criteria for evaluate the construct validity of FACES III
      trough confirmatory factor analysis were established by the researchers. Eight
      criteria were surpassing appropriately and four do not surpass the minimum values
      established. CONCLUSIONS: FACES III in spanish (Mexico) is an instrument with
      reliability of 70% with Cronbach alfa and validity measured using confirmatory
      Factor Analysis. Nevertheless, we found four limitations that should be analyzed
      and evaluated in the planning of future studies.

PMID- 12525339
TI  - [Environmental stress and cardiovascular reactivity: the effect of stressful life
      events on hypertense patients].
AB  - OBJECTIVE: To assess the effect of stressful life events (SLE) on the monitoring
      of patients with essential hypertension. DESIGN: Observational and prospective.
      SETTING: Primary care. PARTICIPANTS: 236 hypertense patients selected by
      systematic randomised sampling. MEASUREMENTS: Age, sex, marital status, cultural
      level, kind of family, presence of SLE, social support, blood pressure, severity
      of hypertension, tobacco consumption, alcohol, presence of diabetes,
      hypercholesterolaemia, body mass index, compliance with hypertension treatment.
      RESULTS. Mean age was 63.51 (62.05; 64.96), with 66.1% being women and 33.9% men.
      48.7% of the patients referred to some SLE during the follow-up. These reached a
      mean of 47.65 (33.16; 62.15) life change units (LCU). Patients with high-impact
      SLE (>150 LCU) had a significant increase of 10.91 mm Hg (0.43; 21.40) in their
      systolic blood pressure and of 9.48 beats per minute (3.78; 15.19) in their heart
      rate, after monitoring for possible factors of confusion. We observed a similar
      trend for diastolic pressure, but this did not reach statistical significance.
      CONCLUSION: The presence of SLE has a negative effect on systolic blood pressure
      in hypertense patients.

PMID- 12525340
TI  - [System of accreditation in primary care (SaAP) (III): challenges in going
      training].

PMID- 12525341
TI  - [Immunization: leaps into the future. Vaccination for bacterial meningitis:
      reality or myth?].

PMID- 12525342
TI  - [Differences between asthma and chronic obstructive disease].

PMID- 12525343
TI  - [The BIFAP project: database for pharmaco-epidemiological research in primary
      care].
AB  - OBJECTIVES: To create a data base (BIFAP) with information provided by primary
      care doctors from the National Health System who use a computer at work, to
      evaluate its validity as a source of pharmaco-epidemiological information and to
      use it for the study of the efficacy and safety of medicines. JUSTIFICATION: Some
      data bases, such as the British GPRD, have shown great efficiency in pharmaco
      epidemiological research and in analysis of alarm signals in pharmacovigilance:
      primary care doctors are in a very good position to obtain clinical information
      from their patients. It is recommended that the impact of medicines on various
      populations is evaluated, including of course those medicines most used in Spain.
      PILOT PHASE: January 2000-end of 2003. 300-500 doctors took part: a) monitoring
      of certain recommendations on recording; b) dispatch every 2 or 3 months to the
      Spanish Medicines Agency (AEM) of anonymous information with its origin encrypted
      (basic demographic details, morbidity, prescriptions, other data of
      epidemiological relevance), which are analysed by computer to check whether they
      meet adequate recording standards; c) despatch to the AEM of copies of anonymous
      clinical reports from small samples of patients (for BIFAP validation studies).
      FEASIBILITY AND PERSPECTIVES: If BIFAP were viable, a standardised procedure for
      its use and protocols to support it as a research tool would be put in place.

PMID- 12525344
TI  - [Immigration, new pathologies: nutritional hypocalcaemic tetany].

PMID- 12525345
TI  - [Aquagenic pruritus due to use of bupropion].

PMID- 12525348
TI  - [Dyspepsia and neuronal networks].

PMID- 12525346
TI  - [Ongoing treatment with omeprazole and appearance of oropharyngeal candidiasis].

PMID- 12525350
TI  - [Hepatitis C, HIV infection and delay in diagnosis].

PMID- 12525352
TI  - [Prone position in adult respiratory distress syndrome: nursing care].
AB  - The use of prone position in patients with Adult Respiratory Distress Syndrome is
      becoming a more and more habitual therapeutic measure in the units of Intensive
      Care, for what to have appropriate Nursing protocols will improve our
      professional performances. This article seeks to modernize knowledge by means of
      the practical experience and the bibliographical revision about Adult Respiratory
      Distress Syndrome, of the prone position and its effects on the organism, as well
      as the prone technique and the Nursing cares of the patients in prone position.
      It is propounded a detailed technique in steps, to carry out the prone position
      in a sure way, an itemized revision on the posture of the patient's maintenance
      in prone position and a Nursing cares protocol for the patients located in this
      posture.

PMID- 12525353
TI  - [Development of a quality guarantee system for mechanical ventilation (register
      in a multi-purpose CCU)].
AB  - OBJECTIVE: 1. Obtaining information about the demographic distribution of
      patients undergoing long-term mechanical ventilation. 2. Defining our reference
      standards for mechanical ventilation, length of UCC and complications related to
      mechanical ventilation (MV), comparable with the international standards.
      Detailed follow-up of pneumonias associated to mechanical ventilation and
      incidence of accidental extubation (AE). DESIGN: Prospective, descriptive. Period
      between July 1998 and December 2000. AREA OF STUDY: Multi-purpose critical care
      unit (12 beds). INDIVIDUALS UNDER STUDY: Patients hospitalized in the critical
      care unit with any pathology in need of mechanical ventilation. RESULTS: During
      the period of study 1058 patients were hospitalized in the critical care unit
      (CCU), 287 (27%) of which needed mechanical ventilation (MV). 29% of the patients
      were women. The age and APACHE II were as median (percentile 25 and 75) 68 (57
      76) and 26 (20-31) respectively. The reasons that made MV necessary were: acute
      respiratory failure 70%, intensified acute exacerbation of chronic respiratory
      failure 11%, coma 18% and neuromuscular illness 1%. The density of average
      incidence of accidental extubation (AE) was 15.7/1000 days of MV, the AE was
      associated to a longer duration of MV, longer stay in CCU and in the hospital and
      a greater incidence of pneumonia associated to MV, but it was not associated to
      an increment in mortality. The density of incidence of pneumonia associated to MV
      was 12.6/1000 days of MV, being the germ more frequently responsible the
      pseudomona aeruginosa.

PMID- 12525354
TI  - [Nursing care in the contrapulsation balloon implantation, maintenance and
      withdrawal].
AB  - Intraaortic pump is used as a mechanical circulatory support device for patients
      with heart failure by means of a lot of causes. Because it requires constant
      attention is used mainly in intensive care units. By inflating and deflating
      intraaortic balloon increases flow to coronary circulation and relieves some of
      the hearts workload. A good synchronization between counterpulsation and the
      patients heartbeat is very important. Nursing cares during this process tries to
      prevent complications originated by the device: blood clots, haemorrhage,
      visceral or limb ischemia, risk of infection.

PMID- 12525357
TI  - [Conservative surgical in oncology].

PMID- 12525358
TI  - [p53 status and response to chemotherapy].
AB  - Numerous studies deal with "p53 status" in patients' tumors (mutated/wild gene
      status, protein level and functionality) to predict chemotherapy efficacy.
      Analyses of various cancers, especially breast cancers, lead to controversy that
      is apparent due to heterogeneity of their design. Recent data from literature
      lead now to consider i) the nature of chemotherapeutic agents and the regimen,
      ii) the cancer tissue type, and iii) the histological response of the primary.
      Molecular actors of senescence, cytostasis and apoptosis, which are responsible
      of cytotoxic response of cancer cells, are currently under elucidation.

PMID- 12525359
TI  - [Functional surgery for head and neck squamous cell carcinoma].
AB  - Surgery for head and neck squamous cell carcinoma can alter speech, swallowing,
      and cosmoses. Recent tendency is to avoid mutilating surgery unless the tumour is
      aggressive or resistant to chemotherapy and or radiotherapy. Functional surgery
      is being widely employed, and for example it may vary between conventional
      partial surgery and endoscopic laser surgery for small sized vocal cord cancers.
      Various new reconstructive procedures have been developed to help early
      functional restoration. Loco-regional flaps can be used to replace gums and avoid
      dental extractions. Free flaps with micro-vascular anastomosis can be employed
      for immediate reconstruction of extensive surgical defects involving pharyngeal
      wall, tongue, mandible and mid-face to restore better function and cosmoses. Few
      recently developed techniques can be also employed in selected cases of laryngo
      pharyngeal cancers to avoid permanent laryngeal mutilation. Another goal of
      functional surgery is to decrease the postoperative radiotherapy or chemo
      radiotherapy sequelae, and obtain successful postoperative functional
      rehabilitation.

PMID- 12525360
TI  - [Conservative management of malignant and borderline ovarian tumor].
AB  - Conservative management of at least a part of one ovary and the uterus, in order
      to preserve fertility-potential, could be propose in most of patients with
      nonepithelial and borderline ovarian tumor. This conservative management could be
      performed even in patients with borderline ovarian tumor associated with
      noninvasive peritoneal implants (if complete resection of peritoneal disease). A
      removal of the preserved ovary after completion of the pregnancy(ies) is not
      necessary if patients agree to a careful follow-up procedure. In patient with
      epithelial ovarian cancer, conservative management could be performed only in
      case of young patients who desire to preserve fertility function with: unilateral
      tumor (stage IA), grade 1 (and 2?), who underwent an adequate staging surgery
      (including peritoneal washings, omentectomy, multiple peritoneal biopsies,
      uterine curettage and complete pelvic and paraaortic lymphadenectomy) and with a
      careful follow-up. A conservative management should not be performed in patients
      with tumor stage > IA and/or grade 3. Removal of preserved ovary should be
      performed after completion of pregnancy(ies) in order to reduce the risk of
      ovarian recurrence.

PMID- 12525361
TI  - [Extended trachelectomy relapse: plea for patient involvement in the medical
      decision].
AB  - A series of 96 radical trachelectomies performed between April 1987 and May 2002
      at Hospital Edouard Herriot in Lyon is reported. One second cancer (bilateral
      suprarenal glands cancer) and four recurrences were observed. The retrospective
      unifactorial analysis demonstrated that the maximal tumoral diameter (2 cm or
      more) and the depth of infiltration (1 cm or more) were the two only significant
      factors of risk (p = 0.001 et p = 0.002 respectively). Age less than 30 years and
      presence of lymphovascular spaces involvement were likely to be factors of risk
      as well but the level of statistical significance was not reached (p = 0.006).
      Histotype other than squamous, infiltration of the parametrium and infiltration
      of the vaginal cuff had no prognosis impact. Adjuvant radiotherapy did not seem
      to lessen the risk. The chances for recurrence were 19% for the patients affected
      by a tumor 2 cm or more and 25% for the patients affected by a tumor 2 cm or more
      with a depth of infiltration 1 cm or more. Should these patients be excluded from
      the indications of radical trachelectomy? The chances for failure do not seem
      lower if the radical option is chosen rather than the conservative one. The
      authors play for a shared decision making.

PMID- 12525362
TI  - [Surgery for rectal cancer: function rather than organ preservation surgery].
AB  - Rectal surgery continues to progress during the last ten years. This technical
      and treatment evolution give the possibility to increase survival, with local
      recurrence decrease, all associated with more digestive, urinary and sexual
      function preservation. These progressive and continues modifications make that
      today the surgeon was a major prognosis factor of success. Whatever the technical
      solution used, the function preservation that we reported here, was more and more
      associated with better oncological result, for the patient benefit. These
      improvements required mixed teams, medical and surgical, implicated in this
      specific cancer giving the possibility to use all the technical solutions
      described here.

PMID- 12525363
TI  - [Soft tissue sarcoma : improved quality of life with new surgical approaches].
AB  - This is a review of diagnostic and therapeutic improvements which have allowed
      quality of life of patients with soft tissue sarcoma.

PMID- 12525364
TI  - [Conservative neurosurgery].
AB  - "Conservative neurosurgery" is an evident concept. Preservation of brain is by
      all means the goal of neurosurgical operations because there are no possibilities
      of compensation in case of lesion of brain parenchyma, either complete or
      partial. However, there is a great variability of functionnally eloquent areas in
      the brain; so a lesion may induce or not visible neurological deficits as
      function of the location of the lesion. The goal of this review article is to
      scan means used in neurosurgery to spare parenchymal brain, which is often called
      "minimal invasive neurosurgery" with a special interest of recent and current
      progress of morphological and functional imaging of the brain.

PMID- 12525365
TI  - [Conservative surgery and restoration after pelvic exenteration].
AB  - Pelvic exenteration can be proposed to non-metastatic patients with advanced or
      recurrent pelvic cancer and remains frequently the only potentially curative
      option in combination with others therapies. Colorectal function preservation and
      reconstructive procedures are useful to decrease functional and psychologic
      impact and postoperative morbidity. Technical procedures including urinary
      diversion, colorectal function preservation, vaginal reconstruction and pelvic
      filling are described and commented. Specific morbidity is analysed.

PMID- 12525366
TI  - [Standards, options and recommendations for the use of medical analgesics for the
      treatment of pain arising from excess nociception in adults with cancer (update
      2002)].
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 the use of medical analgesics for the treatment
      of pain arising from excess nociception in adults with cancer according to the
      definitions of the Standards, Options and Recommendations project. METHODS: In
      1996, a working group, set up by the FNCLCC published clinical practice
      guidelines for pain management in adult and paediatric patients with cancer. In
      the light of the evolution of our knowledge, and practice these guidelines need
      to be updated. The section on "medical analgesic treatments" in the document
      published in 1996 was examined by the working group to identify which questions
      should be updated. These questions and the relevant key words were used to
      develop a search strategy which was used to search Medline , and for particular
      questions, Embase , from January 1994 to March 1999, for relevant references,
      published in English or French. RESULTS: For this update, only a few randomised
      clinical trials were identified, and their conclusions were generally weak. Thus
      much of the information in this document is based on the World Health
      Organisation (WHO) guidelines and represents the "state of the art" on this
      subject in France and is supported by expert agreement. Some changes to the
      original SOR are presented, eg. methods of titration, prescription of new
      opioids, opioid rotation. We also present a synthesis of recent pharmacological
      and regulatory data. The integral version is available on the FNCLCC web site
      (http://www.fnclcc.fr/sor.htm).

PMID- 12525367
TI  - [A project of evidence-based patient information and patient education].

PMID- 12525368
TI  - [Mass breast cancer screening program: a public health priority in France].

PMID- 12525369
TI  - [Information sheet. Mammography].

PMID- 12525370
TI  - [Information sheet. Mammary echography].

PMID- 12525371
TI  - [Information sheet. Stereotaxic biopsies of the breast].

PMID- 12525372
TI  - [Information sheet. Echography-guided biopsy of the breast].

PMID- 12525373
TI  - [Information sheet. Preoperative mammary localization].

PMID- 12525374
TI  - [Prevalence of psychiatric disorders and factors associated with delirium in
      patients referred to a psycho-oncology service].
AB  - The charts of 628 cancer patients, referred to the psycho-oncology service at the
      Hotel-Dieu de Quebec from 1994 to 1997, were reviewed in 1997 to determine the
      nature, the prevalence, and the characteristics of psychiatric diagnoses,
      particularly delirium. Results showed that among patients diagnosed with a
      psychiatric disorder, 54.5% had adjustment disorders, 13.1% suffered from
      delirium and 10.9% from major depression. Statistically significant associations
      were observed between delirium and the use of opioids (odds-ratio (OR): 3.87, 95%
      confidence interval (CI) = 2.28-6.57), corticosteroids (OR = 4.33; CI = 2.34
      8.08), a history of alcoholism (OR = 2.41; CI = 1.27-4.56), being hospitalized
      (OR = 6.10; CI = 2.85-13.08), and being older (OR = 1.06; CI = 1.04-1.08). These
      results confirm the high frequency of psychiatric disorders in patients referred
      for a consultation in psycho-oncology and underline the importance to develop
      such services. Delirium is a major psychiatric complication of cancer and is
      associated with opioids, corticosteroids, alcoholism, being hospitalized, and
      being older.

PMID- 12525376
TI  - Predictors of end stage lung disease in systemic sclerosis.

PMID- 12525377
TI  - Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis
      and is induced by tumour necrosis factor alpha.
AB  - OBJECTIVES: To examine the potential role of the angiogenic growth factor
      angiopoietin-1 (Ang-1) in inflammatory arthritis. METHODS: Eighteen synovial
      tissue samples were obtained from 17 patients with a clinical diagnosis of
      rheumatoid arthritis (RA) and compared with six synovial tissue samples from six
      patients with osteoarthritis (OA). Ang-1 expression in synovial tissues was
      determined by immunohistochemistry and in situ hybridisation. Ang-1 mRNA and
      protein expression were also examined by northern blot analysis and enzyme linked
      immunosorbent assay (ELISA) in cultured synovial fibroblasts and human umbilical
      vein endothelial cells (HUVECs) before and after treatment with tumour necrosis
      factor (TNF)alpha. RESULTS: Ang-1 protein expression was detected by
      immunohistochemistry in 16/18 RA synovial tissue samples. Ang-1 protein was
      frequently observed in the synovial lining layer and in cells within the
      sublining synovial tissue, in both perivascular areas and in areas remote from
      vessels. In contrast, Ang-1 was only weakly detected in these sites in OA
      samples. Ang-1 mRNA and protein were also expressed in cultured synovial
      fibroblasts derived from patients with RA. In addition, induction of Ang-1 mRNA
      and protein was observed by northern blot analysis and ELISA after stimulation of
      RA synovial fibroblasts, but not HUVECs, with the proinflammatory cytokine TNF
      alpha. CONCLUSIONS: Ang-1 mRNA and protein are expressed in the synovium of
      patients with RA, and are up regulated in synovial fibroblasts by TNF alpha. Ang
      1 may therefore be an important regulator of angiogenesis in inflammatory
      arthritis.

PMID- 12525378
TI  - Cytokine production in the infrapatellar fat pad: another source of cytokines in
      knee synovial fluids.
AB  - BACKGROUND: Recent studies have shown that adipose tissue is an endocrine organ
      that releases various cytokines. OBJECTIVE: To investigate the production of
      growth factors and proinflammatory cytokines in infrapatellar fat pad specimens.
      METHODS: Infrapatellar fat pad tissues were obtained from patients during knee
      surgery. Protein levels of basic fibroblast growth factor (bFGF), vascular
      endothelial growth factor (VEGF), tumour necrosis factor (TNF)alpha, and
      interleukin (IL)6 in homogenised tissues were measured by an enzyme immunoassay.
      Gene expressions for those cytokines were examined by reverse transcription
      polymerase chain reaction (RT-PCR). Localisation of bFGF and VEGF was evaluated
      by immunohistochemistry and in situ hybridisation. RESULTS: Infrapatellar fat
      pads were found to contain various protein levels of bFGF, VEGF, TNF alpha, and
      IL6. Further, gene expressions for these cytokines were detected by RT-PCR.
      Immunohistochemistry and in situ hybridisation showed that the expressions of
      both bFGF and VEGF were localised in immature adipocytes, interstitial
      undifferentiated mesenchymal cells, and vascular endothelial cells. CONCLUSION:
      The production of bFGF, VEGF, TNF alpha, and IL6 in the infrapatellar fat pad was
      demonstrated. Although synovial cells and articular chondrocytes are thought to
      be primary sources of cytokines found in knee synovial fluids, the results
      suggest that they may also originate from this fat pad.

PMID- 12525379
TI  - Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production
      in joints of patients with rheumatoid arthritis.
AB  - BACKGROUND: A large number of activated T cells are found in the joints of
      patients with rheumatoid arthritis (RA). Interleukin 7 (IL7), a T cell growth
      factor and a regulator of Th1 and Th2 cytokine production, is produced by
      synoviocytes from patients with RA. OBJECTIVE: To investigate the effect on
      proinflammatory cytokine production of synovial fluid mononuclear cells (SFMC)
      and the mechanism by which IL7 influences CD4+ T cell activity in patients with
      RA. METHODS: In a cross sectional group of patients with RA, IL7 levels were
      compared with those of healthy controls and related to disease activity. The
      effect of IL7 on cytokine production was tested by RA SFMC and on SF CD4+ T cells
      in the presence of mononuclear cells (MC). Production of tumour necrosis factor
      alpha (TNF alpha), IL1 beta, interferon gamma (IFN gamma), and IL4 was measured
      by enzyme linked immunosorbent assay (ELISA) and by single cell FACS analysis.
      Expression of the IL7 receptor alpha chain on CD4+ T cells (essential for IL7
      signalling) was assessed. Direct effects of IL7 on isolated synovial fluid (SF)
      CD4+ T cells were studied by cytokine analysis. By neutralisation of IL12 in MC
      cultures, indirect effects of IL7 on T cells through accessory cells were
      studied. RESULTS: IL7 serum levels were higher in patients with RA than in
      healthy controls and correlated positively with C reactive protein levels. IL7
      stimulated TNFalpha production by SFMC and very potently stimulated IFN gamma and
      TNF alpha production by SF CD4+ T cells. These effects were probably mediated
      through the IL7 receptor alpha chain, which was abundantly expressed on SF CD4+ T
      cells. Besides the direct stimulation of T cell cytokine production by IL7, its
      action was partly dependent on IL12, indicating that IL7 also stimulates
      accessory cell function, leading to T cell activation. CONCLUSION: IL7 stimulates
      proinflammatory cytokine production of intra-articular CD4+ T cells and accessory
      cells from patients with RA. The correlation with measures of disease activity
      indicates that IL7 might substantially contribute to the perpetuation of Th1 and
      TNF alpha mediated proinflammatory responses in patients with RA.

PMID- 12525380
TI  - Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis
      for predicting five year radiographic damage.
AB  - OBJECTIVE: To study the value of antibodies to citrullinated proteins/peptides
      for predicting joint outcomes in patients with recent onset rheumatoid arthritis
      (RA). METHODS: 191 patients with RA onset within the past year were followed up
      prospectively for five years. Serum samples obtained from 145 patients at
      baseline before disease modifying antirheumatic drug treatment were examined
      using three anticitrullinated protein/peptide antibody assays: antiperinuclear
      factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA)
      by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked
      immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline
      and after three and five years were evaluated using Sharp scores modified by van
      der Heijde. RESULTS: Anti-CCP ELISA was positive in 58.9% of patients. APF/anti
      CCP agreement was 77%. The likelihood of a total Sharp score increase after five
      years was significantly greater among patients with anti-CCP antibodies (67%;
      odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR
      2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to
      1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at
      the three times were significantly higher in patients with anti-CCP or APF than
      in those without. AKA did not significantly predict radiographic damage. In
      separate analyses of patients with and without RF, anti-CCP or APF was better
      than RF for predicting total joint damage and joint damage progression after five
      years. CONCLUSION: Antibodies to citrullinated proteins/peptides determined early
      in the course of RA by APF IIF or anti-CCP ELISA are good predictors of
      radiographic joint damage. Further studies of clinical, laboratory, and genetic
      parameters are needed to improve RA outcome prediction in clinical practice.

PMID- 12525381
TI  - Assessment of enthesitis in ankylosing spondylitis.
AB  - OBJECTIVE: To assess, firstly, the validity of the enthesis index published by
      Mander (Mander enthesis index (MEI)) and, secondly, to investigate whether it is
      possible to define a new enthesis index that is less time consuming to perform
      with at least similar or better properties. METHODS: Data from the OASIS cohort,
      an international, longitudinal, observational study on outcome in ankylosing
      spondylitis, were used. In this study, measures of disease activity, including
      the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the MEI, were
      assessed regularly in 217 patients. With the MEI, for each measurement period
      independently, a process of data reduction was performed to identify the entheses
      most commonly reported as painful by the patients. A more concise enthesis index
      was constructed with aid of the entheses found in this way. Correlations with
      measures of disease activity were used to test the validity of several entheses
      indices. RESULTS: Reduction of the number of entheses from 66 to 13 and omitting
      grading of the intensity of pain resulted in an index which was named the
      "Maastricht Ankylosing Spondylitis Enthesitis Score" (MASES). The MASES (range 0
      13) has much greater feasibility than the MEI (range 0-90). However, up to 21% of
      patients with a score >0 on the MEI were not identified by a score on the MASES
      >0. Only 2.1% of the patients with an original enthesis score >0 had an original
      score on the MEI >3 (range 0-90) and it can be questioned whether a low score on
      the MEI index represents clinically important enthesitis. The Spearman
      correlation coefficient between the MASES score and the MEI was 0.90 and between
      the MASES and the BASDAI was 0.53 compared with a correlation of 0.59 between the
      MEI and the BASDAI. CONCLUSIONS: MASES seems to be a good alternative to the MEI
      with much better feasibility.

PMID- 12525382
TI  - Bioenergetics of immune cells to assess rheumatic disease activity and efficacy
      of glucocorticoid treatment.
AB  - OBJECTIVE: To investigate whether activity and glucocorticoid treatment of
      rheumatic diseases are reflected by selected parameters of cellular energy
      metabolism of peripheral blood mononuclear cells (PBMC). METHODS: PBMC were
      obtained from 30 healthy volunteers, 28 patients (16 inactive; 12 active) with
      rheumatoid arthritis, systemic lupus erythematosus, vasculitis, or other
      autoimmune diseases, and five patients with infectious diseases. Patients with
      active rheumatic diseases were examined before and 4-5 days after starting,
      restarting, or increasing the dose of glucocorticoids. Cellular oxygen
      consumption (as a measure of ATP production), bioenergetic ability to be
      stimulated, and major ATP consuming processes were measured amperometrically with
      a Clark electrode. RESULTS: A normal value for oxygen consumption of 3.84 (SEM
      0.1) (all data in nmol O(2)/min/10(7) cells) independent of sex was found. In
      patients with inactive disease the respiration rate was slightly higher, but was
      significantly increased in active patients to 4.82 (SEM 0.33) (p<0.001). PBMC
      from active patients showed a significantly lower bioenergetic response to a
      mitogenic stimulus than controls (p<0.05). In stimulated cells from active
      patients there was a significant reduction in cation transport and protein
      synthesis. All parameters above were almost normalised within 4-5 days upon
      optimised treatment with glucocorticoids. For comparison, PBMC from patients with
      active infectious diseases also showed an increased respiration rate; their
      response to mitogenic stimulation was even higher. CONCLUSIONS: This study shows
      for the first time that parameters describing the cellular function of PBMC in
      bioenergetic terms are suitable for (a) describing semiquantitatively the
      activity of a rheumatic disease and (b) assessing the therapeutic effect on the
      disease.

PMID- 12525383
TI  - Assessment of disability with the World Health Organisation Disability Assessment
      Schedule II in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To investigate in ankylosing spondylitis (AS) whether the newly
      developed World Health Organisation Disability Assessment Schedule II (WHODAS II)
      is a useful instrument for measuring disability, to assess its responsiveness in
      relation to other traditional disease specific instruments, and to identify
      factors that are associated with both short term and long term scores on the
      WHODAS II. METHODS: Patients with AS from a randomised controlled trial assessing
      the efficacy of spa treatment (n=117) and from a five year longitudinal
      observational study (n=97) participated. The patients completed several
      questionnaires, including the WHODAS II. After a three week course of spa
      treatment, 31 patients again completed all questionnaires to assess
      responsiveness. To determine to what degree the WHODAS II reflects some AS
      oriented measures on disease activity, functioning, and quality of life,
      correlation coefficients between the WHODAS II and these other questionnaires
      were calculated. Responsiveness was calculated by the effect size (ES) and
      standardised response mean (SRM). Linear regression analysis was performed to
      explore which factors might be associated with short term changes on the WHODAS
      II and to investigate (in the observational study) which factors of WHODAS II
      might predict disability five years later. RESULTS: Mean score on the WHODAS II
      was 23.9 (SD 15.5 (range 0.0-76.1)). Scores on the WHODAS II were significantly
      correlated with all disease specific questionnaires measured (all p<0.001). The
      WHODAS II showed a comparable short term responsiveness score (SRM 0.41; ES
      0.39). In regression analysis these short term changes on the WHODAS II were
      significantly associated with changes in functioning (beta coefficient 4.25, 95%
      confidence interval (95% CI) 1.24 to 7.26, p=0.007). In the observational study,
      disease activity (beta coefficient 0.35, 95% CI 0.17 to 0.53, p<0.000) as well as
      functioning (beta coefficient 0.23, 95% CI 0.09 to 0.38, p=0.002) seemed to
      significantly predict disability (WHODAS II) after five years. CONCLUSION: The
      WHODAS II is a useful instrument for measuring disability in AS in that it
      accurately reflects disease specific instruments and that it shows similar
      responsiveness scores. In AS, a short term change on the WHODAS II is associated
      with a change in physical function. At the group level, disease activity and
      physical functioning may predict disability after five years.

PMID- 12525384
TI  - Predictors of end stage lung disease in a cohort of patients with scleroderma.
AB  - OBJECTIVES: To estimate the incidence of severe lung disease in patients with
      scleroderma and identify the combination(s) of features present at first
      assessment which would be useful to predict future risk of severe lung disease.
      METHODS: Data were analysed on 561 patients with disease onset occurring on or
      after 1 January 1982 and disease duration of less than five years before the
      first assessment. Detailed clinical and laboratory assessments were undertaken at
      the initial visit. End stage lung disease was defined as pulmonary hypertension
      requiring continuous ambulatory iloprost, or pulmonary fibrosis requiring
      continuous oxygen, or death from a scleroderma related lung disease. Patient
      status was determined at 31 December 1997. The best subset of predictors was
      identified by Cox regression analysis. RESULTS: In all, 24 patients reached end
      stage lung disease. The cumulative incidences were 4%, 6%, and 12% at five,
      seven, and 14 years respectively. As expected, the lung function tests at
      baseline, including being in the lowest third of either diffusing lung capacity
      (hazard ratio (HR) = 18.2, 95% confidence interval (CI) 3.5 to 93.8) or of forced
      vital capacity (HR=4.1, 95% CI 1.1 to 15.2), were highly significant predictors
      of end stage lung disease. Interestingly, apart from the presence of proteinuria,
      none of the other baseline variables, including the extent of skin disease and
      serological markers, were predictive of severe lung disease. CONCLUSION: End
      stage lung disease was infrequent in this large cohort, but the cumulative
      incidence increased importantly with time. The risk can be predicted from
      baseline assessment of pulmonary function. In particular, those with normal
      pulmonary function at baseline are at very low risk.

PMID- 12525386
TI  - Joint consultation of general practitioner and rheumatologist: does it matter?
AB  - OBJECTIVE: To assess the effects of joint consultation on referral behaviour of
      general practitioners (GPs) in a prospective cohort study. METHODS: All patients
      with rheumatological complaints that 17 participating GPs, from the area of the
      University Hospital Maastricht, wanted to refer during a two year inclusion
      period (n=166) were eligible for inclusion. These patients were either referred
      to the outpatient clinic, or presented at a joint consultation held every six
      weeks at the practice of the GP, where groups of three GPs presented their
      patients to a visiting, consulting rheumatologist. The number of patients
      referred by each GP a year at the end of the trial, comparing participating and
      non-participating GPs, was the main outcome measure. RESULTS: During two years of
      inclusion, the 17 participating GPs presented 166 patients. The number of
      patients referred by each GP a year decreased for the participating GPs by 62% at
      the end of the whole study. By contrast, non-participating GPs maintained the
      same rate of referral. The range of diagnoses remained proportionally the same
      throughout the study, with the exception of fibromyalgia. The referral rate of
      this diagnosis decreased significantly (p=0.001). CONCLUSIONS: Joint consultation
      seems to be a good strategy in influencing the referral behaviour of GPs in the
      area of rheumatology. The decrease in referral is substantial and can
      subsequently lead to a reduction of waiting lists.

PMID- 12525385
TI  - Osteoarthritis of finger joints in Finns aged 30 or over: prevalence,
      determinants, and association with mortality.
AB  - BACKGROUND: Prevalence and risk factors of osteoarthritis (OA) in finger joints
      have been amply explored in previous studies. However, no study has focused on
      finger joint OA as a predictor of mortality. OBJECTIVE: To investigate finger
      joint OA for its associations with alleged risk factors and with life expectancy
      in an extensive health survey. METHODS: From 1978 to 1980 a representative
      population sample of 8000 Finns aged 30 years or over was invited to participate
      in a comprehensive health examination; 90% accepted. Hand radiographs were taken
      from 3595 subjects. By the end of 1994, 897 of these had died. RESULTS: The
      prevalence of OA of Kellgren's grade 2 to 4 in any finger joint and in at least
      two symmetrical pairs of distal interphalangeal joints (DIPs) was 44.8% and
      16.0%, respectively. Age and body mass index were significant determinants for OA
      both in any finger joint and in symmetrical DIP OA. The history of physical
      workload in women showed a positive association with OA in any finger joint.
      Smoking in men seemed to protect against symmetrical DIP OA. As adjusted for the
      determinants above, symmetrical DIP OA predicted mortality in women (relative
      risk (RR), 1.23; 95% confidence interval (95% CI) 1.01 to 1.51), but not in men
      (RR 0.89; 95% CI 0.68 to 1.16). In men, however, OA in any finger joint
      significantly predicted cardiovascular deaths (RR 1.42; 95% CI 1.05 to 1.92).
      CONCLUSION: OA in any finger joint and symmetrical DIP OA have different risk
      factor profiles and predict mortality in different patterns between men and
      women.

PMID- 12525387
TI  - Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis
      and polyarteritis nodosa.
AB  - BACKGROUND: Excess cardiovascular mortality complicates systemic rheumatic
      disease, suggesting an accelerated atheromatous process, which it has been
      proposed relates to the vascular inflammation common in such diseases. Impaired
      endothelium dependent vasodilatation is an early marker of atheromatous disease.
      It has previously been shown that such endothelial cell dysfunction (ECD)
      occurring in the brachial artery can complicate primary systemic necrotising
      vasculitis (SNV). OBJECTIVE: To determine if ECD occurs in a wider spectrum of
      primary SNV, if it is restricted to the major arteries, and whether vasculitis
      subgroup, ANCA status, or renal involvement influenced the endothelial responses.
      METHODS: Fifty four patients attending the Birmingham vasculitis clinic,
      including patients with a range of ANCA and non-ANCA associated primary
      vasculitides, and a group of age matched controls were recruited. The length of
      patient follow up and disease activity was variable. Disease activity, damage
      scores, and cardiovascular risk factors were recorded before assessment of flow
      mediated brachial artery vasodilatation by high resolution ultrasound. Dermal
      microvascular responses to acetylcholine were also measured in 32 patients and 21
      controls by laser Doppler flowmetry. RESULTS: ECD was demonstrated in all primary
      SNV subgroups of patients with ANCA associated vasculitis and in polyarteritis
      nodosa, compared with controls. Significant impairment occurred in both vascular
      beds, regardless of vessel size targeted in the inflammatory vasculitis, ANCA
      association and titre, or renal involvement. CONCLUSIONS: Diffuse endothelial
      dysfunction, a predictor of atherosclerotic disease, is found extensively in
      primary systemic vasculitis. Involvement of different vascular beds is
      independent of target vessel size or ANCA association, and is unrelated to local
      disease expression. It is suggested that this results from a systemic response
      that may be a consequence of primary vasculitis, but is distinct from the local
      inflammatory vasculitic process.

PMID- 12525388
TI  - The level of BLyS (BAFF) correlates with the titre of autoantibodies in human
      Sjogren's syndrome.
AB  - BACKGROUND: Increased levels of B lymphocyte stimulator (BLyS) have been detected
      in serum from patients with systemic lupus erythematosus and rheumatoid
      arthritis. OBJECTIVE: To determine the level of BLyS in serum from patients with
      primary's Sjogren's syndrome (SS), another autoimmune disease in which B cell
      activation is high. METHODS: Serum samples from 49 patients with primary SS
      according to the revised European criteria were assayed for BLyS, quantitative
      immunoglobulins, and autoantibody levels and compared with samples from 47
      healthy control subjects. RESULTS: The median level of BLyS was 5.99 ng/ml (25th
      75th centile range 3.20-8.93 ng/ml) in SS v 2.49 ng/ml (25th-75th centile range
      1.96-2.96 ng/ml) in healthy controls (p<0.001). More importantly, among patients
      with SS, the presence of anti-SSA antibodies was associated with significantly
      higher levels of BLyS (medians 7.90 ng/ml v 3.70 ng/ml; p=0.008) as was the
      presence of anti-SSB antibodies (medians 7.14 ng/ml v 3.70 ng/ml; p=0.02) and of
      rheumatoid factor (medians 7.70 ng/ml v 3.80 ng/ml; p=0.016). The level of BLyS
      in three patients with a monoclonal gammopathy was higher than in the other
      patients (medians 26.53 ng/ml v 5.92 ng/ml; p=0.13). Higher levels of BLyS were
      associated with higher levels of gammaglobulins and IgG. There was a strong
      correlation between BLyS and rheumatoid factor level (r=0.71, p<0.0001), anti-SSA
      IgG level (r=0.32, p=0.02) and anti-SSA IgM level (r=0.39, p=0.006). CONCLUSION:
      In human SS the level of BLyS correlates with the level of autoantibodies. Thus,
      BLyS may play a part in activating specific autoreactive B cells and modulating
      the level of production of autoantibodies which are the hallmark of the disease.
      These findings raise the possibility of a novel therapeutic approach in human SS.

PMID- 12525389
TI  - Transforming growth factor beta 1 and insulin-like growth factor 1 block collagen
      degradation induced by oncostatin M in combination with tumour necrosis factor
      alpha from bovine cartilage.
AB  - Oncostatin M (OSM) in combination with tumour necrosis factor alpha (TNF alpha)
      promotes marked collagen breakdown from bovine cartilage in explant culture. This
      release was dependent upon matrix metalloproteinases and could be prevented by
      transforming growth factor beta 1 (TGF beta 1) or insulin-like growth factor 1.
      Both growth factors reduced the expression and secretion of collagenase enzymes,
      and TGF beta 1 induced tissue inhibitor of metalloproteinase production. This
      study shows for the first time that these anabolic growth factors can protect
      cartilage against OSM+TNF alpha induced destruction.

PMID- 12525390
TI  - Fibrosis regression induced by intravenous gammaglobulin treatment.
AB  - OBJECTIVES: To review case histories of patients in whom fibrosis played a
      significant role in the pathogenesis of their disease, and to determine whether
      intravenous gammaglobulin (IVIg) contributed to the regression of their fibrotic
      condition. METHODS: Eight patients with excess fibrotic reaction in the course of
      diverse diseases were analysed; a tendency that reverted with different IVIg
      treatment options. Myelofibrosis was predominant in three patients (a patient
      with a myeloproliferative syndrome, one with systemic lupus erythematosus, and
      one with Sjogren's syndrome). Three patients had scleroderma as their main
      feature, one patient had hepatitis C cirrhosis, and one had idiopathic
      thrombocytopenic purpura. RESULTS: Fibrotic excess was reduced in all the
      patients by IVIg treatment. In five patients the disease as a whole benefited
      from the infusion of immunoglobulins. CONCLUSION: IVIg may enhance resorption of
      fibrosis and promote healing in patients with fibrotic associated disorders.

PMID- 12525391
TI  - Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis
      evaluated by Doppler ultrasonography.
AB  - OBJECTIVE: to estimate and visualise the efficacy of treatment with etanercept
      (Enbrel) in patients with rheumatoid arthritis (RA) using colour Doppler and
      spectral Doppler ultrasonography to determine the possible changes in synovial
      perfusion during a one year observation period. METHODS: Eleven patients from the
      European multicentre trial of the efficacy and safety of etanercept were included
      in this study when transferred into the open label, long term safety, and
      efficacy study. Before a scheduled dosage increase to 50 mg/week they were
      examined clinically, serologically, and by ultrasonography using the colour
      Doppler pixels and the spectral Doppler resistance index (RI) as indicators of
      inflammation. The patients were re-examined at two weeks and at one year follow
      up RESULTS: The clinical activity decreased significantly from baseline to week
      2, but no significant changes were seen from baseline to one year. The number of
      coloured pixels in each region of interest decreased from baseline to week 2 with
      a median reduction of 60% (p=0.005). This effect on the perfusion in the synovium
      could not be found after one year of treatment. During the initial treatment we
      detected an increase in synovial RI by spectral Doppler. The median increase in
      peripheral resistance from baseline to week 2 as estimated by the mean RI was
      22.6% (p=0.005). The increase in peripheral resistance was maintained to some
      extent after one year (mean RI increased by 18.8% p=0.074). CONCLUSION:
      Ultrasonography seems to be a promising tool for the detection of treatment
      response using spectral Doppler and pixel estimation.

PMID- 12525392
TI  - Protein kinase signals activate interleukin 16 encoding transcripts in rheumatoid
      arthritis versus osteoarthritis synovial fibroblasts.

PMID- 12525393
TI  - Obstructive sleep apnoea as a cause of fatigue in ankylosing spondylitis.

PMID- 12525394
TI  - Thoracic high resolution computed tomography in patients with ankylosing
      spondylitis and without respiratory symptoms.

PMID- 12525395
TI  - Effect of low dose weekly methotrexate on bone mineral density and bone turnover.

PMID- 12525396
TI  - Evaluation of a screening tool for inflammatory joint disease.

PMID- 12525397
TI  - Anti-annexin V antibodies in patients with cerebrovascular disease.

PMID- 12525398
TI  - Intra-alveolar haemorrhage in temporal arteritis.

PMID- 12525400
TI  - It's time to focus on the quality of GME.

PMID- 12525399
TI  - Circulating soluble CD40 ligand in patients with eosinophilic fasciitis.

PMID- 12525401
TI  - Limitations on residents' working hours at New York teaching hospitals: a status
      report.
AB  - Teaching hospitals in New York have been subject to regulations that limit the
      working hours of residency trainees since July 1989. Following a period of
      enhanced survey activity by the State Department of Health in the late 1990s, the
      state awarded a contract to a third-party organization to conduct annual audits
      of the state's teaching hospitals to assess compliance with the regulations. As
      of October 2002, preliminary results indicate that 75 of the 118 teaching
      hospitals in the state (63.6%) were found to be out of compliance with some
      component of the regulations. The most common citations for noncompliance were
      (1) working in excess of 24 consecutive hours (45%), and (2) working in excess of
      80 hours per week, averaged over four weeks (28%). For New York teaching
      hospitals, the key factors identified as posing significant challenges to
      achieving full compliance with the regulations included (1) assuming
      responsibility for the work schedules of residents; (2) scheduling and monitoring
      difficulties; (3) the education efforts associated with the regulations; (4) the
      documentation requirements; (5) variations in learning abilities among the
      residents; and (6) mistaking verbal compliance for actual compliance. As the
      state begins a new round of surveys, it will be expecting better compliance
      efforts, and New York teaching hospitals are committed to this difficult but
      worthy goal.

PMID- 12525402
TI  - Residents' duty hours in the province of Ontario, Canada.
AB  - The author explains the history of the Professional Association of Internes and
      Residents of Ontario (PAIRO), Canada, founded in 1968-69 to represent
      postgraduate medical trainees in negotiations with the Ontario Hospital
      Association over issues of trainees' stipends. Over the years, the negotiations
      evolved to cover a number of other issues, including duty hours, and established
      the principle that binding arbitration would be used to resolve any disputes
      between the two parties that could not be resolved through negotiation. At
      present, PAIRO negotiates a biannual collective agreement with the Ontario
      Council of Teaching Hospitals (OCOTH), whose features the author describes. The
      most important provisions of the 2000-2002 PAIRO-OCOTH agreement on the limits of
      duty hours are described. The author then comments that while such limits have
      benefited programs and residents, there is concern that the limits decrease the
      opportunities for trainees to be involved in the care of patients with a wide
      variety of medical conditions. Also, the duty-hours limits have required some
      services to use attending physicians or outside health professionals to perform
      duties previously carried out by trainees, creating problems that the author
      describes.

PMID- 12525403
TI  - Residents' duty hours in the province of Quebec, Canada.
AB  - The author describes the five decades of efforts by residents in the medical
      schools of the province of Quebec, Canada, to negotiate scientific, cultural,
      social, and economic issues that affect them as trainees. At present, the
      residents' association, the Federation des Medecine residents du Quebec
      negotiates collective agreements on working conditions and other issues with the
      Quebec Ministry of Health, not the hospital association. The federation has
      become recognized as an important body throughout Canada, and its representatives
      regularly participate in meetings concerning the country's health care system.
      The author describes the duty hours provisions of the current collective
      agreement (1996-2002), and remarks that in general, the agreement's regulations
      are helpful to residents, prevent the possibility of abusive work schedules, and,
      among other benefits, provide generous time off for conferences, examinations,
      and study time. However, some residents, particularly those in surgical
      disciplines, believe that the work-hours provisions are too restrictive, as they
      wish to maximize their acute-care surgical experiences in the operating room via
      frequent on-call hours. At present, residents in all disciplines are allowed to
      remain in the hospital to attend to patient care duties as much as they wish, but
      they may not be on official call more than is stipulated by the collective
      agreement. These agreements have also created some difficulties in providing
      coverage for patients; the author discusses various solutions to this problem.

PMID- 12525404
TI  - Addressing the new competencies for residents' surgical training.
AB  - In July 2001 the Accreditation Council for Graduate Medical Education (ACGME)
      charged U.S. residency training programs to implement a curriculum and evaluation
      plan covering six competencies. The authors describe the curriculum and
      evaluation strategy of the first surgical training program developed to meet the
      competencies, and list each competency and the teaching method and measurement
      instruments used. Implementation began July 1, 2001, and the program was fully
      operational on July 1, 2002. Meeting the curriculum challenges required
      modification of the existing curriculum and the addition of new instructional
      units. Nine additional evaluation instruments were needed. The largest investment
      was in planning and implementation, a one-time development cost. Staff workload
      increased by 252 hours; this is expected to be a continuing annual requirement.
      Faculty workload increased by two hours per resident and each resident's workload
      increased by 112 hours per year (2.3 hours per week). The transition was smoother
      than expected. Faculty and residents' buy-in was crucial. Faculty and residents
      were alerted to upcoming changes at the beginning of the year in a grand rounds
      presentation on the ACGME competencies and the approach to meeting requirements.
      Updates were presented periodically. The authors recommend that residency
      programs engaged in similar efforts make effective use of instruments developed
      elsewhere and collaborate with other programs rather than develop everything
      locally. The program's benefits include time savings and the availability of
      validity data and norms to inform decision making on residents' and program
      progress.

PMID- 12525405
TI  - Does the osteopathic internship have a future?
AB  - Since 1984, a new set of realities has generated pressures that are transforming
      osteopathic graduate medical education (OGME) and forcing it to adapt to changing
      circumstances. Policy decisions were made that addressed these circumstances, and
      the impact of these choices moved OGME in new directions. Many of the changes
      were perceived as positive, but inherent weaknesses were exposed as well. While
      the appearance and structure of OGME have been significantly altered, nowhere are
      the changes more apparent than in the traditional osteopathic internship.
      Compared with 1990, today's osteopathic internship is markedly different in terms
      of its curriculum, its identity, and its place within residencies approved by the
      Accreditation Council for Graduate Medical Education. As a direct consequence of
      decisions made to expand internship opportunities, the traditional osteopathic
      internship appears destined to vanish as a distinct educational experience.

PMID- 12525406
TI  - Teaching professionalism to residents.
AB  - The need to teach professionalism during residency has been affirmed by the
      Accreditation Council for Graduate Medical Education, which will require
      documentation of education and evaluation of professionalism by 2007. Recently
      the American Academy of Pediatrics has proposed the following components of
      professionalism be taught and measured: honesty/integrity,
      reliability/responsibility, respect for others, compassion/empathy, self
      improvement, self-awareness/knowledge of limits, communication/collaboration, and
      altruism/advocacy. The authors describe a curriculum for introducing the above
      principles of professionalism into a pediatrics residency that could serve as a
      model for other programs. The curriculum is taught at an annual five-day retreat
      for interns, with 11 mandatory sessions devoted to addressing key professionalism
      issues. The authors also explain how the retreat is evaluated and how the
      retreat's topics are revisited during the residency, and discuss general issues
      of teaching and evaluating professionalism.

PMID- 12525407
TI  - Using role playing to increase residents' awareness of medical student
      mistreatment.
AB  - The teacher-learner relationship is subject to both internal and external
      influences that may lead to mistreatment and harassment of the student. The
      student who is mistreated may mistreat students when he or she becomes a teacher.
      The author describes an experiential program for residents at Brown Medical
      School from 1999 to 2002 in which residents, through role playing, helped produce
      teaching videotapes on medical student mistreatment. Fourteen residents had
      participated in the program to date. They reported that they had benefited from
      an increased awareness of the effects of student mistreatment and had learned how
      to handle mistreatment more effectively. They also reported increased sensitivity
      to others and improved self-awareness, qualities that they planned to incorporate
      into their professional identities and that should help them avoid mistreatment
      of students and residents later in their careers. Because preventing mistreatment
      from being transmitted to the next generation is an important way to increase
      medical professionalism, the author recommends that role-playing exercises
      dealing with mistreatment be a part of all residency education.

PMID- 12525408
TI  - Preparing graduates for the first year of residency: are medical schools meeting
      the need?
AB  - PURPOSE: Changes in graduate medical education associated with full
      implementation of the Balanced Budget Act of 1997 have required medical schools
      to review and revise their curricula. As limited funding increases pressures to
      streamline training, residencies will potentially expect an entry level of skill
      and competence that is greater than that which schools are currently providing.
      To determine whether medical school curricular requirements correlate with
      residency needs, this multidisciplinary pilot study investigated expectations and
      prerequisites for postgraduate specialty training. METHOD: A questionnaire about
      100 skills and competencies expected of new first-year residents was sent to 50
      U.S. residency directors from surgery, internal medicine, family medicine,
      pediatrics, and obstetrics-gynecology programs. Each director was asked to state
      expectations of a first-year resident's competence in each skill at entry to
      residency and after three months of training. Skills deemed most appropriately
      acquired in residency were also identified. Competencies included diagnosis,
      management, triage, interpretation of data, informatics and technology, record
      keeping, interpersonal communications, and manual skills. RESULTS: A total of 39
      residency directors responded, including seven surgery, nine medicine, seven
      family medicine, eight pediatrics, and eight obstetrics-gynecology. In addition
      to physical examination skills, 13 competencies achieved more than 70% agreement
      as being entry-level skills. There was wide variability as to the relative
      importance of the remaining skills, with residency directors expecting to devote
      significant resources and time in early training to ensure competence.
      CONCLUSIONS: Medical schools should consider the expectations of their students'
      future residency directors when developing new curricula. Assuring students'
      competencies through focused curricular change should save both time and
      resources during residency.

PMID- 12525409
TI  - The effect of a teaching hospital's financial crisis and reorganization on a
      group of residents.
AB  - PURPOSE: Allegheny General Hospital (AGH) in Pittsburgh, Pennsylvania, was part
      of a statewide health care system that underwent a financial crisis and
      operational reorganization between 1998 and 2000. This study assessed internal
      medicine (IM) residents' perceptions of the effects of AGH's financial crisis on
      their residencies METHOD: A confidential, program-based questionnaire was
      distributed to 75 IM residents at AGH in spring 2000 and included questions on
      demographic information, inpatient and outpatient medical education, and the
      hospital's financial crisis. Residents were asked to assess the effects of the
      financial crisis on their residencies, personal experiences, and attitudes toward
      health care systems. Outcomes included consideration of transfer, recommendation
      of the program to a medical student, concerns about fellowship opportunities,
      opinions about large health care systems, and medicine as a career
      recommendation. RESULTS: A total of 71 residents (95%) responded to the
      questionnaire. Fifty-five (79%) had experienced effects on their residencies due
      to the financial crisis, but perceptions differed widely. Eighteen (25%)
      considered transferring from the program, but 44 of 59 (75%) would have
      recommended the program to a medical student. Because of the financial crisis,
      respondents reported significant changes in concerns about fellowship
      opportunities (p <.001), opinions about large health care systems (p <.001), and
      opinions about recommending medicine as a career (p <.001). CONCLUSION: This
      study highlights the fact that residents serve as program ambassadors and their
      experiences may influence recruitment and retention. Thus, programs should
      consider ways to assess and address residents' concerns during any system crisis
      or reorganization.

PMID- 12525410
TI  - Research support infrastructure and productivity in U.S. family practice
      residency programs.
AB  - PURPOSE: To examine the associations between 11 research support infrastructural
      characteristics and measures of research productivity. METHOD: A questionnaire
      was mailed to 462 directors of non-military family practice residency programs in
      the United States. A total of 11 research support infrastructural characteristics
      and six research productivity measures were coded. Initial analyses indicated a
      skewness in responses given by larger versus smaller programs. Respondents were
      divided into those from programs with eight or fewer full-time faculty and those
      from programs with nine or more. Separate analyses were run for each. Logistic
      regression was employed to determine which research support characteristics would
      best predict productivity in the top quartile. RESULTS: Of the 461 recipients of
      deliverable questionnaires, 351 (76.1%) responded. A large proportion of programs
      reported no research productivity for the preceding 12 months. Separate stepwise
      logistic regression analyses were run for small and large programs; the ability
      of the 11 characteristics to predict research-productive programs varied with
      size. Employment of full-time research professionals was the only characteristic
      positively associated with research productivity for both groups. For small
      programs, research productivity was positively associated with the requirement of
      faculty members to do research. For large programs, it was positively associated
      with both the presence of fellowship programs and the presence of a specific,
      written research strategic plan. CONCLUSION: This study demonstrated a positive
      association between several elements of research infrastructure and research
      productivity but that such infrastructure is inconsistent across programs and
      seemingly insufficient to develop the necessary research culture and
      socialization.

PMID- 12525411
TI  - A systematic review of resident research curricula.
AB  - PURPOSE: To review in a systematic manner the published curricula for training
      house officers in research. METHOD: Articles were identified by searching the
      Medline, Educational Resources Information Center, and Science Citation Index
      databases, educational Web sites, and bibliographies of captured articles, and by
      contacting experts who had developed resident research curricula. Demographic
      information, curriculum development steps, educational strategies, evaluation
      methods, and outcomes were abstracted. RESULTS: The search identified 41 articles
      describing curricula. The most common curricular objectives were to increase
      house officers' research productivity and improve their critical appraisal
      skills. Only one curriculum was designed with the goal of producing academic
      physicians. Among many instructional methods, conducting research projects,
      exposing learners to role models or mentors, and providing house officers with
      multiple opportunities to present their work were common. Only 27 articles (66%)
      articulated goals or objectives, and 11 included (27%) needs assessments.
      Evaluation methods were often rudimentary, frequently limited to learners' self
      assessments or authors' anecdotal reports. Five (12%) reported pre-post
      intervention testing of learners' knowledge. No curricula were evaluated as
      prospective pretest-posttest controlled trials. A minority of articles reported
      costs, obstacles encountered, or modifications made in the curriculum.
      CONCLUSION: Successful educational interventions should incorporate needs
      assessments, clearly defined learning objectives, and evaluation methods. While
      many curricula for resident research exist, the lack of detailed developmental
      information and meaningful evaluations hinders educators interested in adopting
      these curricula.

PMID- 12525412
TI  - Anxiety and anger among family practice residents: a South Carolina family
      practice research consortium study.
AB  - PURPOSE: To study the dimensions of anxiety and anger experienced by a statewide
      sample of South Carolina family practice residents. METHOD: A total of 350 family
      practice residents from seven programs participated. Each resident completed the
      Beck Depression Inventory, the State-Trait Anxiety Inventory, the Profile of Mood
      States, the Hassles Scale, the Maslach Burnout Inventory, and the State-Trait
      Anger Expression Inventory (STAXI) on at least one occasion. We analyzed reported
      anxiety and anger by gender, year of training, race, marital status, type of
      program (community hospital versus university), location of program, and season
      of the year. RESULTS: Residents reported lower levels of anxiety and anger across
      most dimensions compared with the adult populations on which the tests were
      standardized and with other resident and practicing physician populations. The
      residents did not demonstrate excessive levels of anger as a trait or in response
      to situations, nor did they significantly suppress anger. Although the residents
      reported a higher frequency of hassles than did normal populations, they did not
      consider these hassles severe. A higher than normal level of depersonalization
      was found among male, Caucasian, and third-year residents. CONCLUSIONS: These
      family medicine residents did not experience excessive levels of anxiety or anger
      during residency training either as a trait, state or somatic response. Extensive
      social and emotional "in-house" support, attention to stress-management skills,
      and the moderate personality characteristics of family practice residents help
      explain these findings. Initial assessment of psychological functioning and early
      remediation and program support during training may significantly reduce the
      potential for residents' impairment.

PMID- 12525413
TI  - Medical students' perceptions of their housestaffs' ability to teach physical
      examination skills.
AB  - PURPOSE: To evaluate the amount of time housestaff spent at the bedside on
      physical examination skills with third-year medical students and whether
      housestaff enhanced physical examination skills. METHOD: All Albert Einstein
      College of Medicine students who completed the third-year medicine inpatient
      clerkship at one of five participating sites evaluated housestaff (interns and
      residents) with whom they spent at least ten days. The students quantified the
      amount of time housestaff spent with them at the bedside and used a modified five
      point Likert scale to evaluate housestaff's enhancement of students' physical
      examination skills. Data were analyzed separately for interns, but pooled for
      residents (years two and three). Differences between groups were tested using
      Wilcoxon rank-sum and by Mantel-Haenszel chi-square tests. RESULTS: Totals of 191
      responses for interns and 166 responses for residents were collected from October
      1999 to October 2000. Fifteen (8%) of the intern group and 59 (36%) of the
      resident group spent no time at the bedside (p <.0001). Students were most
      satisfied with enhancement of pulmonary, cardiovascular, and gastrointestinal
      skills and least satisfied with enhancement of ENT, eye, and genitourinary skills
      (p <.0001). CONCLUSIONS: Interns spent more time with students than did
      residents. Almost one third of the residents spent no time on physical
      examination skills with students. Training programs should re-emphasize the
      importance of housestaff's teaching at the bedside and address areas of
      deficiency.

PMID- 12525414
TI  - Didactic teaching conferences for IM residents: who attends, and is attendance
      related to medical certifying examination scores?
AB  - PURPOSE: Didactic teaching conferences are a cornerstone of residents' training
      in internal medicine, yet these programs have received little formal evaluation.
      This study determines the factors associated with residents' attendance at
      didactic teaching conferences and the relationship of attendance to residents'
      scores on medical certification examinations. METHOD: The attendance of 81
      residents was recorded at 199 conferences at one university hospital's internal
      medicine residency program during the 1996-97 academic year. Characteristics of
      the conferences were recorded, including the date, whether lunch was provided,
      the daily census on the medicine general wards, daily ambient temperature, and
      conference type. Residents' scores on the United States Medical Licensing
      Examination (USMLE) Step 2 and American Board of Internal Medicine (ABIM)
      certification examination were collected. RESULTS: Residents' attendance at
      conferences was 34% overall or 54% excluding excused absences. Adjusting for the
      conferences' and residents' characteristics, attendance declined by one third as
      the year progressed. Providing lunch at noon conferences enhanced residents'
      attendance (odds ratio [OR] 1.26 overall and OR 1.64 for residents on inpatient
      rotations). Higher attendance was not associated with improvement in standardized
      medical knowledge test scores. CONCLUSIONS: Absenteeism and waning attendance
      through the year have important implications for structuring didactic internal
      medicine teaching. Providing lunch improves attendance, but this incentive should
      be weighed against the potential burdens of the pharmaceutical industry's funding
      of these lunches. The lack of relationship between attendance and residents'
      adjusted board scores calls for a better understanding of the value of this high
      intensity medical education intervention.

PMID- 12525416
TI  - Measuring outcomes of undergraduate medical education: residency directors'
      ratings of first-year residents.
AB  - PURPOSE: There is a growing recognition of the need to show the relationship
      between undergraduate medical education (UME) and achievements during residency.
      This study provides reliability and validity evidence for a residency rating
      scale as well as a method for gathering comparison information about first-year
      residents. METHOD: A 25-item rating scale measuring important areas of physician
      functioning was mailed to residency directors of 485 graduates of the 1998-2000
      classes of the University of Kansas School of Medicine. The same rating scale was
      sent to residency directors for a comparison sample of 251 graduates of other
      U.S. medical schools who were residents at the University of Kansas Medical
      Center. Each item on the rating scale was rated on a five-point Likert scale.
      Principal-components analysis, correlational analyses, internal consistency
      reliability analysis, and mean comparisons were used to provide evidence of
      reliability and validity. RESULTS: A total of 382 (82%) usable rating scales were
      returned. A principal-components analysis extracted five factors that accounted
      for 86% of the variance. The final factors were (1) interpersonal communication,
      (2) clinical skills, (3) population-based health care, (4) record-keeping skills,
      and (5) critical appraisal skills. The internal consistency of the entire scale
      was.98, with coefficients for the five factors ranging from.92 to.97. The
      correlations between the five factors and measures of undergraduate performance
      ranged from.21 to.49. Group analyses revealed that residents with high GPAs and
      USMLE Step 1 and Step 2 scores tended to be rated higher than those with lower
      scores. CONCLUSIONS: The rating scale demonstrated adequate reliability and
      validity and showed that residency directors' ratings are a useful outcome
      measure for UME performance.

PMID- 12525417
TI  - The privilege of practicing medicine.

PMID- 12525418
TI  - Assessing students' performances in a competency-based curriculum.
AB  - Brown Medical School embarked on planning a competency-based curriculum in 1989.
      The curriculum was fully implemented in 1996, effective for the MD class of 2000.
      To graduate, a student must (1) demonstrate mastery of the medical knowledge
      base, (2) achieve beginning and intermediate levels of proficiency in nine key
      abilities, and (3) attain an advanced level in the ability called "problem
      solving" and three other abilities that the student chooses based on his or her
      interests. The nine abilities are effective communication; basic clinical skills;
      using basic science in the practice of medicine; diagnosis, management, and
      prevention; lifelong learning; self-awareness, self-care, and personal growth;
      the social and community contexts of health care; moral reasoning and clinical
      ethics; and problem solving. As a major educational innovation, the new
      competency-based curriculum has been successfully woven into the fabric of the
      medical school learning environment. In this article, the authors describe how
      faculty go about assessing students' performances relative to the nine abilities.

PMID- 12525419
TI  - Thomas Eakins' "The Gross Clinic" (1875).

PMID- 12525421
TI  - AAMC policy guidance on graduate medical education: assuring quality patient care
      and quality education.
AB  - This document, approved by the executive council of the Association of American
      Medical Colleges at its September 2001 meeting, provides policy guidance on the
      four key issues requiring attention by teaching hospitals, medical schools, and
      leaders and faculty of graduate medical education (GME) programs: (1)
      institutional oversight and program support; (2) the educational program; (3)
      supervision of residents in patient care; and (4) residents' duty hours. These
      issues require urgent attention by the academic community. The quality of
      residents' education and the well-being of residents themselves are among
      academic medicine's most solemn professional obligations. Persistent calls for
      reforming GME to better meet these obligations must be heeded, not because
      government regulation is the likely alternative if they are not, but because it
      is the right thing to do. Implementing the guidelines will require many
      sponsoring institutions and individual training programs to allocate additional
      resources to their GME missions, which will pose a major challenge to many,
      partly because many payers of patient care services are reluctant to assume their
      fair share of GME costs and also because there are regulatory constraints that
      affect GME within current public programs. Sponsors of GME programs should find
      these policy guidelines helpful in setting priorities for the expenditure of
      existing resources.

PMID- 12525422
TI  - Human papillomavirus and cervical cancer.
AB  - Of the many types of human papillomavirus (HPV), more than 30 infect the genital
      tract. The association between certain oncogenic (high-risk) strains of HPV and
      cervical cancer is well established. Although HPV is essential to the
      transformation of cervical epithelial cells, it is not sufficient, and a variety
      of cofactors and molecular events influence whether cervical cancer will develop.
      Early detection and treatment of precancerous lesions can prevent progression to
      cervical cancer. Identification of precancerous lesions has been primarily by
      cytologic screening of cervical cells. Cellular abnormalities, however, may be
      missed or may not be sufficiently distinct, and a portion of patients with
      borderline or mildly dyskaryotic cytomorphology will have higher-grade disease
      identified by subsequent colposcopy and biopsy. Sensitive and specific molecular
      techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk
      HPV types have been introduced as an adjunct to cytology. Earlier detection of
      high-risk HPV types may improve triage, treatment, and follow-up in infected
      patients. Currently, the clearest role for HPV DNA testing is to improve
      diagnostic accuracy and limit unnecessary colposcopy in patients with borderline
      or mildly abnormal cytologic test results.

PMID- 12525423
TI  - Concepts in immunology and diagnosis of hydatid disease.
AB  - Echinococcosis is a cosmopolitan zoonosis caused by adult or larval stages of
      cestodes belonging to the genus Echinococcus (family Taeniidae). The two major
      species of medical and public health importance are Echinococcus granulosus and
      E. multilocularis, which cause cystic echinococcosis (CE) and alveolar
      echinococcosis (AE), respectively. Both CE and AE are both serious diseases, the
      latter especially so, with a high fatality rate and poor prognosis if managed
      inappropriately. This review discusses new concepts and approaches in the
      immunology and diagnosis of CE, but comparative reference has also been made to
      AE infection and to earlier pivotal studies of both diseases. The review
      considers immunity to infection in the intermediate and definitive hosts, innate
      resistance, evasion of the immune system, and vaccination of intermediate and
      definitive hosts, and it particularly emphasizes procedures for diagnosis of CE
      and AE, including the value of immunodiagnostic approaches. There is also
      discussion of the new advances in recombinant and related DNA technologies,
      especially application of PCR, that are providing powerful tools in the fields of
      vaccinology and molecular diagnosis of echinococcosis.

PMID- 12525424
TI  - Ehrlichia chaffeensis: a prototypical emerging pathogen.
AB  - Ehrlichia chaffeensis is an obligately intracellular, tick-transmitted bacterium
      that is maintained in nature in a cycle involving at least one and perhaps
      several vertebrate reservoir hosts. The moderate to severe disease caused by E.
      chaffeensis in humans, first identified in 1986 and reported for more than 1,000
      patients through 2000, represents a prototypical "emerging infection." Knowledge
      of the biology and natural history of E. chaffeensis, and of the epidemiology,
      clinical features, and laboratory diagnosis of the zoonotic disease it causes
      (commonly referred to as human monocytic ehrlichiosis [HME]) has expanded
      considerably in the period since its discovery. In this review, we summarize
      briefly the current understanding of the microbiology, pathogenesis, and clinical
      manifestations associated with this pathogen but focus primarily on discussing
      various ecological factors responsible for the recent recognition of this
      important and potentially life-threatening tick-borne disease. Perhaps the most
      pivotal element in the emergence of HME has been the staggering increases in
      white-tailed deer populations in the eastern United States during the 20th
      century. This animal serves as a keystone host for all life stages of the
      principal tick vector (Amblyomma americanum) and is perhaps the most important
      vertebrate reservoir host for E. chaffeensis. The contributions of other
      components, including expansion of susceptible human populations, growth and
      broadening geographical distributions of other potential reservoir species and A.
      americanum, and improvements in confirmatory diagnostic methods, are also
      explored.

PMID- 12525425
TI  - Molecular host-pathogen interaction in brucellosis: current understanding and
      future approaches to vaccine development for mice and humans.
AB  - Brucellosis caused by Brucella spp. is a major zoonotic disease. Control of
      brucellosis in agricultural animals is a prerequisite for the prevention of this
      disease in human beings. Recently, Brucella melitensis was declared by the
      Centers for Disease Control and Prevention to be one of three major bioterrorist
      agents due to the expense required for the treatment of human brucellosis
      patients. Also, the economic agricultural loss due to bovine brucellosis
      emphasizes the financial impact of brucellosis in society. Thus, vaccination
      might efficiently solve this disease. Currently, B. abortus RB51 and B.
      melitensis REV.1 are used to immunize cattle and to immunize goats and sheep,
      respectively, in many countries. However, these genetically undefined strains
      still induce abortion and persistent infection, raising questions of safety and
      efficiency. In fact, the REV.1 vaccine is quite virulent and apparently unstable,
      creating the need for improved vaccines for B. melitensis. In addition, Brucella
      spp. may or may not provide cross-protection against infection by heterologous
      Brucella species, hampering the acceleration of vaccine development. This review
      provides our current understanding of Brucella pathogenesis and host immunity for
      the development of genetically defined efficient vaccine strains. Additionally,
      conditions required for an effective Brucella vaccine strain as well as the
      future research direction needed to investigate Brucella pathogenesis and host
      immunity are postulated.

PMID- 12525428
TI  - Herpes simplex virus resistance to acyclovir and penciclovir after two decades of
      antiviral therapy.
AB  - Acyclovir, penciclovir, and their prodrugs have been widely used during the past
      two decades for the treatment of herpesvirus infections. In spite of the
      distribution of over 2.3 x 10(6) kg of these nucleoside analogues, the prevalence
      of acyclovir resistance in herpes simplex virus isolates from immunocompetent
      hosts has remained stable at approximately 0.3%. In immuncompromised patients, in
      whom the risk for developing resistance is much greater, the prevalence of
      resistant virus has also remained stable but at a higher level, typically 4 to
      7%. These observations are examined in the light of characteristics of the virus,
      the drugs, and host factors.

PMID- 12525427
TI  - Recent progress in herpes simplex virus immunobiology and vaccine research.
AB  - Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic
      infections that have serious outcomes in some individuals. Neonatal herpes may
      occur when the infant traverses the cervix during maternal genital herpes.
      Genital herpes is a major risk factor for human immunodeficiency virus type 1
      transmission. Considerable efforts have been made to design and test vaccines for
      HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines
      based on HSV-2 envelope glycoproteins have reached advanced-phase clinical
      trials. These antigens were chosen because they are the targets of neutralizing
      antibody responses and because they elicit cellular immunity. Encouraging results
      have been reported in studies of treatment of HSV-seronegative women with a
      vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant.
      Because most sexual HSV transmission occurs during asymptomatic shedding, it is
      important to evaluate the impact of vaccination on HSV-2 infection, clinically
      apparent genital herpes, and HSV shedding among vaccine recipients who acquire
      infection. There are several other attractive formats, including subunit vaccines
      that target cellular immune responses, live attenuated virus strains, and mutant
      strains that undergo incomplete lytic replication. HSV vaccines have also been
      evaluated for the immunotherapy of established HSV infection.

PMID- 12525426
TI  - Herpes simplex virus type 1 and bovine herpesvirus 1 latency.
AB  - Primary infection by herpes simplex virus type 1 (HSV-1) can cause clinical
      symptoms in the peripheral and central nervous system, upper respiratory tract,
      and gastrointestinal tract. Recurrent ocular shedding leads to corneal scarring
      that can progress to vision loss. Consequently, HSV-1 is the leading cause of
      corneal blindness due to an infectious agent. Bovine herpesvirus 1 (BHV-1) has
      similar biological properties to HSV-1 and is a significant health concern to the
      cattle industry. Latency of BHV-1 and HSV-1 is established in sensory neurons of
      trigeminal ganglia, but latency can be interrupted periodically, leading to
      reactivation from latency and spread of infectious virus. The ability of HSV-1
      and BHV-1 to reactivate from latency leads to virus transmission and can lead to
      recurrent disease in individuals latently infected with HSV-1. During latency,
      the only abundant HSV-1 RNA expressed is the latency-associated transcript (LAT).
      In latently infected cattle, the latency-related (LR) RNA is the only abundant
      transcript that is expressed. LAT and LR RNA are antisense to ICP0 or bICP0,
      viral genes that are crucial for productive infection, suggesting that LAT and LR
      RNA interfere with productive infection by inhibiting ICP0 or bICP0 expression.
      Numerous studies have concluded that LAT expression is important for the latency
      reactivation cycle in animal models. The LR gene has recently been demonstrated
      to be required for the latency-reactivation cycle in cattle. Several recent
      studies have demonstrated that LAT and the LR gene inhibit apoptosis (programmed
      cell death) in trigeminal ganglia of infected animals and transiently transfected
      cells. The antiapoptotic properties of LAT map to the same sequences that are
      necessary for promoting reactivation from latency. This review summarizes our
      current knowledge of factors regulating the latency-reactivation cycle of HSV-1
      and BHV-1.

PMID- 12525429
TI  - Pathogenic human viruses in coastal waters.
AB  - This review addresses both historical and recent investigations into viral
      contamination of marine waters. With the relatively recent emergence of molecular
      biology-based assays, a number of investigations have shown that pathogenic
      viruses are prevalent in marine waters being impacted by sewage. Research has
      shown that this group of fecal-oral viral pathogens (enteroviruses, hepatitis A
      viruses, Norwalk viruses, reoviruses, adenoviruses, rotaviruses, etc.) can cause
      a broad range of asymptomatic to severe gastrointestinal, respiratory, and eye,
      nose, ear, and skin infections in people exposed through recreational use of the
      water. The viruses and the nucleic acid signature survive for an extended period
      in the marine environment. One of the primary concerns of public health officials
      is the relationship between the presence of pathogens and the recreational risk
      to human health in polluted marine environments. While a number of studies have
      attempted to address this issue, the relationship is still poorly understood. A
      contributing factor to our lack of progress in the field has been the lack of
      sensitive methods to detect the broad range of both bacterial and viral
      pathogens. The application of new and advanced molecular methods will continue to
      contribute to our current state of knowledge in this emerging and important
      field.

PMID- 12525431
TI  - Time to reflect on the Women's Health Initiative (WHI) study.

PMID- 12525432
TI  - The ovarian endometrioma: why is it so poorly managed? Laparoscopic treatment of
      large ovarian endometrioma: why such a long learning curve?
AB  - The laparoscopic management of ovarian endometrioma was reported more than 15
      years ago. An anonymous survey conducted among gynaecologists in the UK showed
      that 50% of ovarian endometrioma are still managed by laparotomy. This surprising
      result is discussed emphasizing the difficulties of the learning curve, pitfalls
      in surgical training and mistakes of the pioneers. Endoscopic surgery will become
      the standard technique when all practising gynaecologic surgeons have been
      trained during their residency. The goal of the endoscopic surgeon should be to
      achieve adequate surgical treatment. Endoscopic surgery is not a technical
      gimmick used to avoid laparotomy and to attract patients.

PMID- 12525433
TI  - Investigation of the infertile couple: should diagnostic laparoscopy be performed
      in the infertility work up programme in patients undergoing intrauterine
      insemination?
AB  - Diagnostic laparoscopy is normally the standard procedure performed as the final
      test in the infertility work up before progressing to infertility treatment.
      Recently, there has been a growing tendency to bypass diagnostic laparoscopy
      after a normal hysterosalpingogram and instead to start direct infertility
      treatment [intrauterine insemination (IUI) or IVF] for indications such as
      unexplained infertility, male subfertility and cervical hostility. In our clinic,
      laparoscopy revealed abnormalities that resulted in changed treatment decisions
      in 25% of the patients who would normally have been scheduled for IUI if
      laparoscopy had not been performed. The changed treatments mainly concerned
      surgery for minimal/mild endometriosis and periadnexal adhesions, both performed
      during the diagnostic laparoscopy. Because the effect of such interventions on
      the success rate of IUI has never been described, it still remains unclear
      whether laparoscopy is usefully performed in these cases. Therefore, further
      prospective studies should be performed to assess whether delaying, or bypassing
      entirely, diagnostic laparoscopy is more cost effective and if laparoscopic
      interventions for intra-abdominal abnormalities are effective in terms of higher
      pregnancy rates after treatment with IUI.

PMID- 12525434
TI  - Number of germ cells and somatic cells in human fetal testes during the first
      weeks after sex differentiation.
AB  - BACKGROUND: This study presents the number of germ cells and somatic cells in
      human fetal testes during week 6 to week 9 post conception, i.e. the first weeks
      following sex differentiation of the testes. METHODS: One testis with attached
      mesonephros from each of 10 individual legal abortions was used. After recovery
      of the fetus, the testes were immediately isolated, fixed and processed for
      histology. The optical fractionator technique, a stereological method, was
      utilized to estimate the total number of germ cells in ten testes and somatic
      cells in six of them. RESULTS: The number of germ cells per testis increased from
      approximately 3000 in week 6 to approximately 30000 in week 9. The ratio of germ
      cells to Sertoli cells was approximately 1:11 and the ratio of germ cells to
      somatic cells was approximately 1:44 throughout this period. CONCLUSIONS: For the
      first time, germ cell and somatic cell number have been determined during early
      human fetal testis development. Knowledge of the number of germ cells in this
      period may be very important, because several environmental pollutants are
      suspected to result in decreased semen quality in men born of mothers exposed to
      these pollutants during pregnancy.

PMID- 12525435
TI  - Human peripheral blood mononuclear cells enhance cell-cell interaction between
      human endometrial epithelial cells and BeWo-cell spheroids.
AB  - BACKGROUND: Previously, it was reported that T-lymphocytes derived from non
      pregnant mice promote murine embryo implantation. In order to examine the
      immunological regulation of endometrial receptivity in humans, the effects of
      peripheral blood mononuclear cells (PBMCs) on endometrial epithelial cell (EEC)
      function were monitored by a newly developed attachment assay using primary human
      EEC culture and BeWo cell-derived spheroids. METHODS AND RESULTS: EECs isolated
      from 25 women in the mid- and late proliferative and early, mid- and late
      secretory phases were subjected to monolayer culturing. Spheroids were
      constructed from BeWo cells, a human choriocarcinoma cell line, by incubation
      with continuous rolling, after which their interaction with cultured EECs was
      studied. The mean (+/- SEM) number of attached spheroids was significantly higher
      (P < 0.01) in the EEC culture derived from women in the mid-secretory phase (90
      +/- 2.9%) than the other groups (ranging from 0 to 5.8 +/- 3.7%), which is in
      agreement with the existence of a so-called 'implantation window'. After 72 h co
      culture of EECs with PBMCs, the number of attached spheroids significantly
      increased in the EEC cultures derived from the late proliferative and early
      secretory phases [65.0 +/- 21.7 versus 5.0 +/- 2.0% (P < 0.05) and 83.1 +/- 4.1
      versus 4.4 +/- 1.9% (P < 0.01)]. CONCLUSIONS: This attachment assay appears to be
      a useful method with which to assess endometrial receptivity. Functional change
      of EECs induced by PBMCs suggests possible regulation of endometrial receptivity
      by immune cells.

PMID- 12525436
TI  - Preliminary report on nitric oxide-mediated oxidative damage in adolescent
      varicocele.
AB  - BACKGROUND: The current study was designed to characterize the process of nitric
      oxide (NO) and peroxynitrite generation through the determination of
      nitrotyrosine concentration in the dilated veins of varicoceles in adolescents.
      METHODS: Ten adolescents with a median age of 13 years (range 12-17) affected by
      a left idiopathic varicocele (grade II and III) were studied. Whole blood samples
      were withdrawn from a peripheral vein at time of induction of anaesthesia, and
      from a dilated spermatic vein before ligation. Peripheral blood samples from five
      adolescents undergoing minor surgical procedures were used as controls. The
      nitrotyrosine concentration was evaluated by a sandwich enzyme-linked
      immunosorbent assay (ELISA), using a monoclonal anti-nitrotyrosine antibody and
      Western blot analysis. RESULTS: Plasma nitrotyrosine concentrations were
      significantly greater in the spermatic vein when compared with the peripheral
      vein (P = 0.031). Nitrotyrosine in plasma of controls did not show any
      significant difference in comparison with peripheral samples from varicocele
      patients. Western blot analysis confirmed the above data. CONCLUSIONS: In
      adolescents with a varicocele, there is an increase in nitrotyrosine
      concentration within the spermatic vein that can cause protein nitration and
      cytotoxicity via its reaction with various molecular targets. This could have
      repercussions on both sperm and testis function. We conclude that an oxidative
      stress status is present and should be considered as an indication for varicocele
      treatment in the adolescent.

PMID- 12525430
TI  - Indoor mold, toxigenic fungi, and Stachybotrys chartarum: infectious disease
      perspective.
AB  - Damp buildings often have a moldy smell or obvious mold growth; some molds are
      human pathogens. This has caused concern regarding health effects of moldy indoor
      environments and has resulted in many studies of moisture- and mold-damaged
      buildings. Recently, there have been reports of severe illness as a result of
      indoor mold exposure, particularly due to Stachybotrys chartarum. While many
      authors describe a direct relationship between fungal contamination and illness,
      close examination of the literature reveals a confusing picture. Here, we review
      the evidence regarding indoor mold exposure and mycotoxicosis, with an emphasis
      on S. chartarum. We also examine possible end-organ effects, including pulmonary,
      immunologic, neurologic, and oncologic disorders. We discuss the Cleveland infant
      idiopathic pulmonary hemorrhage reports in detail, since they provided important
      impetus for concerns about Stachybotrys. Some valid concerns exist regarding the
      relationship between indoor mold exposure and human disease. Review of the
      literature reveals certain fungus-disease associations in humans, including
      ergotism (Claviceps species), alimentary toxic aleukia (Fusarium), and liver
      disease (Aspergillys). While many papers suggest a similar relationship between
      Stachybotrys and human disease, the studies nearly uniformly suffer from
      significant methodological flaws, making their findings inconclusive. As a
      result, we have not found well-substantiated supportive evidence of serious
      illness due to Stachybotrys exposure in the contemporary environment. To address
      issues of indoor mold-related illness, there is an urgent need for studies using
      objective markers of illness, relevant animal models, proper epidemiologic
      techniques, and examination of confounding factors.

PMID- 12525437
TI  - Tissue integrity is essential for ectopic implantation of human endometrium in
      the chicken chorioallantoic membrane.
AB  - BACKGROUND: Not all women with patent tubes develop clinically manifest
      endometriosis. Quality and quantity of endometrium in retrograde menstruation may
      be the determining factor in the development of the disease. We hypothesize that
      retrograde shedding of endometrial fragments with preserved integrity facilitates
      implantation of endometrium in ectopic locations, resulting in endometriotic
      lesion development. We evaluate the impact of tissue integrity on the success of
      endometriosis-like lesion development in the chicken embryo chorioallantoic
      membrane (CAM) model. METHODS: Menstrual and non-menstrual (cyclic) endometrium
      were collected by biopsy, and either minced or enzymatically dispersed.
      Spontaneously shed menstrual effluent was collected by a menstrual cup, and cells
      and tissue were isolated. We evaluated whether infiltration or lesion formation
      in the CAM occurred after transplantation of endometrium onto the CAM. RESULTS:
      Transplantation of biopsied menstrual and cyclic endometrium fragments, and of
      endometrium fragments >1 mm(3) isolated from menstrual effluent, resulted in
      lesion formation. Transplantation of endometrial cells isolated from menstrual
      effluent did not lead to lesion formation. After transplantation of digested
      biopsied cyclic endometrium, infiltration in the CAM but no lesions were
      observed. CONCLUSION: In the CAM assay, integrity of tissue architecture
      determines success of implantation of human endometrium in ectopic locations.

PMID- 12525438
TI  - Prospective analysis of the relationships between the ovarian follicle cohort and
      basal FSH concentration, the inhibin response to exogenous FSH and ovarian
      follicle number at different stages of the normal menstrual cycle and after
      pituitary down-regulation.
AB  - BACKGROUND: Analyses of the follicular reserve and activity of the ovary are
      central to our understanding of the regulation of follicular development. We have
      carried out a prospective analysis of endocrine and biophysical assessments under
      three differing basal conditions: the early follicular and mid-luteal phases, and
      following GnRH analogue down-regulation. METHODS: Hormonal analyses were carried
      out before and after a single dose of FSH on spontaneously ovulating women (n =
      58). Ovarian volume and antral follicle count (AFC) were also determined.
      RESULTS: Inhibin B and estradiol concentrations were increased by FSH under all
      three conditions, and inhibin A in the follicular phase and after down
      regulation. Basal hormone concentrations, except inhibin A and B after down
      regulation, did not generally correlate with AFC. A close relationship between
      inhibin B and AFC was evident at all stages after FSH administration (r = 0.70
      0.77). AFC and inhibin B after FSH stimulation were well correlated with the
      number of oocytes recovered after superovulation. Multivariate analysis
      demonstrated that inhibin B after FSH administration in the down-regulated state
      showed the closest correlation with oocyte number. In the more clinically useful
      early follicular and luteal phases, basal FSH was the most significant
      contributor to the number of oocytes, with a significant contribution from luteal
      phase AFC. CONCLUSIONS: These data extend our understanding of the relationships
      between follicular number, follicular functional activity, and the recruitable
      follicular population. Down-regulation and subsequent FSH stimulation was
      required to clearly demonstrate the close relationship between inhibin B and the
      ovarian reserve. Without such complex manipulation, early follicular phase FSH
      (supplemented by AFC in the relatively hypogonadotrophic luteal phase) remains of
      greater value in predicting the ovarian reserve than the currently known direct
      products of the ovary.

PMID- 12525439
TI  - Ovarian stimulation by clomiphene citrate and hMG in combination with cetrorelix
      acetate for ICSI cycles.
AB  - BACKGROUND: The introduction of GnRH antagonists such as cetrorelix acetate has
      made possible the simplification of ovarian stimulation. However, the most
      effective protocol for their administration has not yet been clearly defined.
      METHODS: Forty women with male-factor infertility undergoing 40 ICSI cycles were
      included in the study. Clomiphene citrate at 100 mg a day was given from cycle
      day 3 through day 7. hMG at 150 IU was given on cycle days 4, 6 and 8, and was
      adjusted from day 9 according to the follicular and hormone responses. Cetrorelix
      acetate at 2.5 mg was administered when the leading follicle reached 14 mm. The
      remaining 0.5 mg was divided into two 0.25 mg injections for possible later use.
      Serum FSH, LH, estradiol and progesterone levels were measured daily from the day
      of cetrorelix acetate injection until hCG was given. RESULTS: Serum LH level was
      suppressed effectively for 4 days. Four patients (10%) needed one or two
      additional injections of 0.25 mg cetrorelix acetate. No premature LH surge was
      detected in any of the women treated. Sixteen women became pregnant (40%), of
      which 14 pregnancies (35%) were ongoing at the time of writing. CONCLUSIONS: This
      study demonstrates that this new protocol is feasible for couples with male
      factor infertility undergoing ICSI.

PMID- 12525440
TI  - Development and characterization of a long-acting recombinant hFSH agonist.
AB  - BACKGROUND: Fusion of the carboxyterminal peptide (CTP) of hCG to FSH results in
      a follitropin agonist with an extended half-life, presumably due to the four O
      oligosaccharides on the CTP. Alternatively, an rhFSH analogue containing
      additional N-linked carbohydrate is described in this report. METHODS: A DNA
      sequence containing two N-oligosaccharide signal sequences was ligated into a
      vector containing hFSHbeta- and alpha-subunit encoding cDNA, and expressed in CHO
      K1 cells. In-vitro bioactivity of the single-chain hormone was assessed in CHO
      cells expressing the hFSH receptor. Pharmacokinetic values were derived from
      serial serum assays of the analogue in immature female rats following a single
      i.v. injection. In-vivo bioactivity was assessed by measuring ovarian weight gain
      3 days post-injection. RESULTS: rhFSH-N2 and native rhFSH induced comparable
      levels of cAMP in vitro. t(1/2) for native rhFSH, rhFSH-CTP and rhFSH-N2 were
      3.7, 7.1 and 7.3 h respectively. Rats receiving rhFSH-N2 had a mean +/- SD
      ovarian weight 3 days post-i.v. injection (22 +/- 3.6 mg) significantly greater
      than rats receiving rhFSH and saline (16.7 +/- 1.5 and 15.3 +/- 0.47 mg
      respectively, P < 0.05). CONCLUSIONS: rhFSH-N2 has prolonged half-life and
      increased bioactivity compared with native rhFSH. This rhFSH agonist, and other
      analogues containing additional N-oligosaccharides may have important clinical
      applications.

PMID- 12525441
TI  - Low-dose combination of flutamide, metformin and an oral contraceptive for non
      obese, young women with polycystic ovary syndrome.
AB  - BACKGROUND: The endocrine-metabolic status of non-obese, young women with
      polycystic ovary syndrome (PCOS) is normalized more effectively by combined
      treatment with flutamide and metformin than by either of these drugs in
      monotherapy. In this follow-up study, we assess whether the endocrine-metabolic
      benefits of combined flutamide-metformin treatment are maintained in the presence
      of a low-dose oral contraceptive (OC). METHODS: To a population of non-obese,
      young PCOS women already receiving flutamide-metformin (125 mg/day and 1275
      mg/day), a low-dose OC (ethinyl estradiol 20 microg + gestodene 75 microg) was
      administered to reduce the risk of pregnancy. A total of 12 women elected to
      receive the OC and this subgroup (OC+) was matched to a subgroup continuing on
      flutamide-metformin alone (OC-), for a total study population of 24 women (mean
      age +/- SEM 18.7 +/- 0.3 years; body mass index, 21.8 +/- 0.5 kg/m(2)). Endocrine
      metabolic indices were assessed before any treatment (0 months), on flutamide
      metformin (12 months), and again after a further 6 months with or without
      additional OC (18 months). RESULTS: In OC- and OC+ women, the beneficial effects
      of flutamide-metformin on hyperandrogenaemia, hyperinsulinaemia and dyslipidaemia
      were maintained. In OC+ women, there was an additional increase in sex hormone
      binding globulin (SHBG), and thus a further drop in the free androgen index.
      CONCLUSION: When a low-dose OC is administered with a low-dose flutamide
      metformin combination in women with PCOS, the beneficial effects are maintained
      on hyperinsulinaemia-dyslipidaemia, which are key determinants of long-term
      complications. Hence, in daily practice, such a low-dose quatuor may become a
      therapeutic option of first choice for young women with PCOS.

PMID- 12525442
TI  - Effect of long-term treatment with low-dose mifepristone on the endometrium.
AB  - BACKGROUND: Mifepristone in low daily doses has contraceptive potential by
      inhibiting ovulation and menstruation. Because follicular development is
      maintained, the endometrium is exposed to estrogen for prolonged periods
      unopposed by progesterone. METHODS: Endometrial biopsies were collected from 90
      women in Edinburgh and Shanghai before (late proliferative) and 60 and 120 days
      after taking 2 or 5 mg mifepristone per day for 120 days. RESULTS: Ovulation and
      menstruation were inhibited in >90% of cycles and estrogen production was similar
      to that observed during the follicular phase of the control cycle. By 120 days,
      endometrial thickness increased significantly in women in Edinburgh but decreased
      in Shanghai. Endometrial histology showed inactive proliferative or cystic
      changes with dense stroma. There was a significant decrease in markers of
      proliferation, i.e. mitotic index and Ki67 staining. There were no pregnancies in
      a total of 200 women-months in 50 sexually active women who used no other method
      of contraception. CONCLUSIONS: We confirm that ovulation and menstruation were
      suppressed in the majority of cycles and there was asynchrony between ovarian
      activity and endometrial histology, which showed no signs of hyperplasia or
      atypia. These preliminary data suggest that daily low-dose mifepristone is
      potentially a safe estrogen-free contraceptive pill which has the added health
      benefit of amenorrhoea.

PMID- 12525443
TI  - Low-dose antiprogestin treatment prevents pregnancy in rhesus monkeys and is
      reversible after 1 year of treatment.
AB  - BACKGROUND: Administration of low doses of an antiprogestin to rhesus monkeys
      permits ovarian/menstrual cyclicity, suppresses endometrial proliferation and
      prevents pregnancy without adverse or toxic side-effects after 5-6 months of
      daily treatment. The purpose of this study was to test the reversibility with
      respect to restoration of fertility after 1 year of low-dose antiprogestin
      treatment. METHODS: This experiment included a daily 1 year vehicle- or
      antiprogestin-treatment interval followed by a 9 month post-treatment interval
      for adult, female rhesus monkeys (n = 5/group) of proven fertility and exhibiting
      regular menstrual cycles. Co-habitation occurred with a male of proven fertility
      and vaginal swabs were taken to identify the presence of sperm during the
      treatment (antiprogestin females) and post-treatment intervals (vehicle and
      antiprogestin females). RESULTS: Mating and vaginal sperm were evident in all
      antiprogestin females during, and, in both groups, after treatment. Based on
      ultrasonography, none of the antiprogestin-treated females became pregnant during
      the treatment interval. However, upon cessation of treatment, pregnancy rates
      were similar between antiprogestin-treated (3/5) relative to vehicle-treated
      (4/5) females with live, healthy infants born in both groups. There were no
      differences between groups in fetal measurements, gestation lengths, live birth
      rates and infant weights. CONCLUSIONS: The reversal of the anti-fertility effects
      of chronic, low-dose antiprogestin treatment supports the clinical feasibility of
      potent and selective antiprogestins as potential contraceptives for women.

PMID- 12525444
TI  - Hormonally mediated disturbance of angiogenesis in the human endometrium after
      exposure to intrauterine levonorgestrel.
AB  - BACKGROUND: The levonorgestrel intrauterine system (LNG-IUS) is a contraceptive
      device that is used for treatment of menorrhagia. The system induces inter
      menstrual bleeding within the first few months after insertion. We hypothesized
      that this bleeding might be associated with a change in vascular development.
      METHODS: A randomized, controlled study was undertaken on 48 women. RESULTS:
      Hysterectomy specimens were obtained and immunocytochemistry was carried out with
      antibodies to CD31, alpha-smooth muscle actin and myosin. Stereological
      measurement of blood vessels was also undertaken. Most vessels appeared normal,
      including the arterioles. Large thin-walled vessels were present in the
      superficial endometrium of the treated group but were almost completely absent in
      the controls. The distribution of cytoskeletal markers revealed well-formed basal
      arterioles with more widespread expression in the superficial stroma than was
      found in untreated tissue. The volume fraction of blood vessels (P = 0.0001), the
      number of vessel cross-sections per unit area (P = 0.0003) and the cross
      sectional diameters of the largest vascular lumens (P = 0.0001) were
      significantly increased following treatment with LNG-IUS. However, there was no
      difference in the median values of vessel diameter or the vascular surface
      density. CONCLUSION: These findings suggest that the LNG has a localized effect
      on some vessels within the superficial endometrium.

PMID- 12525445
TI  - Auditory brainstem response in premenopausal women taking oral contraceptives.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the effects of the
      new monophasic oral contraceptives on the audiological system in premenopausal
      women. METHODS: The auditory brainstem response (ABR) was measured in 94 women
      during the follicular, periovular and luteal phases of one menstrual cycle in
      which ovulation was confirmed using sonography and serum progesterone
      concentration. The latencies for waves I, III and V were determined, and the
      inter-peak intervals were calculated for waves I-III, I-V and III-V. All 94 women
      began taking oral contraceptives: 23 women used 20 microg ethinyl estradiol (EE)
      plus 150 microg desogestrel, 24 women used 30 microg EE plus 75 microg gestodene,
      and 47 women used 15 microg EE plus 60 microg gestodene. During the third month
      of contraceptive intake, each subject was again tested for ABR, as above.
      RESULTS: The wave latencies and inter-peak intervals showed shorter values during
      the periovular phase with respect to the luteal phase (P < 0.05), the follicular
      phase for wave I and for inter-peak interval I-V (P < 0.05) of the menstrual
      cycle. All of the ABR results in pill users were statistically different from
      those of the periovular phase (P < 0.05), though similar to those of both the
      luteal and follicular phases (P = NS). CONCLUSIONS: ABR seems to depend on the
      variations of ovarian steroids during the menstrual cycle and during oral
      contraceptive intake.

PMID- 12525446
TI  - Fertility preservation in breast cancer patients: IVF and embryo cryopreservation
      after ovarian stimulation with tamoxifen.
AB  - BACKGROUND: Breast cancer chemotherapy commonly causes premature ovarian failure
      and infertility. Because increased estrogen levels are thought to be potentially
      risky in breast cancer patients, natural cycle IVF (NCIVF) has been used to
      preserve fertility and treat infertility in these women. METHODS: Twelve women
      with breast cancer received 40-60 mg tamoxifen for 6.9 +/- 0.6 days beginning on
      days 2-3 of their menstrual cycle (15 cycles), and had IVF (TamIVF) with either
      fresh embryo transfer (six cycles) or cryopreservation (nine cycles). They were
      compared to a retrospective control group (n = 5) who had natural cycle IVF
      (NCIVF, nine cycles). RESULTS: Cycle cancellation was significantly less frequent
      in TamIVF, compared with NCIVF (1/15 versus 4/9, P < 0.05). Compared with NCIVF,
      TamIVF patients had a greater number of mature oocytes (1.6 +/- 0.3 versus 0.7 +/
      0.2, P = 0.03) and embryos (1.6 +/- 0.3 versus 0.6 +/- 0.2, P = 0.02) per
      initiated cycle. TamIVF resulted in the generation of embryo(s) in every patient
      (12/12) while only three out of five patients had an embryo following NCIVF. Two
      out of six patients in TamIVF, and 2/5 in NCIVF conceived. One patient in the
      TamIVF group delivered a set of twins. After a mean follow up of 15 +/- 3.6
      months (range 3-54), none of the patients had a recurrence of cancer.
      CONCLUSIONS: Tamoxifen stimulation appears to result in a higher number of
      embryos and may provide a safe method of IVF and fertility preservation in breast
      cancer patients.

PMID- 12525447
TI  - Successful conception following Fallopian tube recanalization in infertile
      patients with a unilateral proximally occluded tube and a contralateral patent
      tube.
AB  - BACKGROUND: There are many published case reports of successful conception
      following transcervical Fallopian tube recanalization (T-FTR) in patients with
      bilateral proximally occluded Fallopian tubes. However, no serial trials have
      been published with respect to successful conception following unilateral tubal
      recanalization in infertile patients with a unilateral proximally occluded tube
      and a contralateral patent tube. This study was designated to analyse the success
      rate of T-FTR and the pregnancy rate due to natural fertilization in the lumen of
      the recanalized tube in these patients. METHODS: We have encountered only 11
      patients with this abnormality in our department in the past 10 years. T-FTR with
      fluoroscopic guidance was performed in these patients, confirmed by at least two
      hysterosalpingographies to exclude tubal spasm. The uterine catheter devised by
      us was used during the procedure. RESULTS: All 11 Fallopian tubes were
      successfully opened by T-FTR. In the six patients who conceived, a preovulatory
      follicle was demonstrated on the side of the cannulated tube during the
      conception. The success rate of recanalization, the pregnancy rate due to
      fertilization in the lumen of the recanalized tube and the successful delivery
      rate were 100, 55 and 36% respectively. CONCLUSIONS: Our findings suggest that a
      functional and/or organic disorder in the patent tube resulted in infertility in
      patients with unilateral proximal tubal obstruction. Our results further show
      that recanalization of occluded tubes is an effective treatment. Thus,
      recognition of successful conception following T-FTR in these patients will be
      beneficial to our clinical approach to this infertile condition.

PMID- 12525449
TI  - Induction of spermatogenesis in azoospermic men after varicocele repair.
AB  - BACKGROUND: The purpose of this study was to assess the treatment outcome after
      varicocele repair in azoospermic men and to correlate this outcome with the
      testicular histology patterns. METHODS: Medical records of 15 azoospermic men who
      underwent testis biopsy and microsurgical repair of clinical varicocele between
      July 1999 and November 2000 were reviewed. All patients had at least two semen
      analyses showing azoospermia taken before the surgery and two semen analyses post
      operatively. Hypospermatogenesis was identified in four, maturation arrest in
      six, and germ cell aplasia in five men. RESULTS: Induction of spermatogenesis was
      achieved in seven men (47%). Of these, four had germ cell aplasia and three had
      maturation arrest. The improvement in sperm concentration and motility in
      patients with germ cell aplasia ranged from 1.8 to 7.9 x 10(6)/ml, and from 32 to
      76% respectively. Of these seven patients with improvement in semen quality, five
      relapsed into azoospermia 6 months after the recovery of spermatogenesis (four
      germ cell aplasia and one maturation arrest). One patient with maturation arrest
      established a pregnancy. CONCLUSIONS: Azoospermic patients may have an
      improvement in semen quality following varicocelectomy. Semen samples should be
      cryopreserved after an initial improvement following varicocelectomy, as relapse
      to a state of azoospermia may occur.

PMID- 12525448
TI  - 17beta-Estradiol and environmental estrogens significantly affect mammalian sperm
      function.
AB  - BACKGROUND: Compounds with estrogenic activity can affect reproductive function
      in mammals. This study investigated possible effects of 17beta-estradiol (E(2))
      and three weakly estrogenic environmental estrogens on mammalian sperm
      capacitation and fertilizing ability in vitro. METHODS: Uncapacitated and
      capacitated mouse sperm suspensions were incubated for 30 min in the presence of
      E(2), genistein (Gen), 8-prenylnaringenin (8-PN) and nonylphenol (NP), and then
      assessed using chlortetracycline (CTC) fluorescence analysis. In addition,
      treated uncapacitated sperm suspensions were tested for changes in fertilizing
      ability. RESULTS: In uncapacitated cells, E(2) at >or=1 micromol/l and Gen, 8-PN
      and NP at >or=0.001 micromol/l, significantly stimulated capacitation and
      acrosome reactions. Hydroxytamoxifen (an estrogen antagonist) did not inhibit
      responses to any of these compounds. In capacitated cells, E(2) had no effect,
      but the other three compounds significantly stimulated acrosome reactions. Added
      to uncapacitated suspensions, 10 micromol/l E(2), 0.1 micromol/l Gen and 0.1
      micromol/l 8-PN all significantly stimulated sperm fertilizing ability (
      approximately 76% oocytes fertilized) compared with untreated control sperm (
      approximately 36%). CONCLUSIONS: This study provides the first evidence that E(2)
      and environmental estrogens can significantly stimulate mammalian sperm
      capacitation, acrosome reactions and fertilizing ability, with the environmental
      estrogens being much more potent than E(2). The inability of hydroxytamoxifen to
      block these responses suggests that classical estrogen receptors may not be
      involved. Whether these responses have effects on fertility in vivo remains to be
      determined, along with the mechanisms of action involved.

PMID- 12525450
TI  - Recombinant human albumin supports hamster in-vitro fertilization.
AB  - BACKGROUND: Serum albumin is normally required to support sperm capacitation and
      IVF, but its mechanism of action is not well understood. Commercial serum albumin
      preparations are contaminated with a variety of other proteins and compounds, and
      their biological activity is variable. Recombinant human albumin (rHA) might
      replace serum albumin for IVF. METHODS: rHA was examined for its ability to
      capacitate hamster spermatozoa and to support fertilization in vitro. A
      standardized hamster IVF system was used to compare the capacitation-supporting
      activities of rHA and two commercial preparations of bovine serum albumin (BSA)
      in a chemically defined culture medium. Epididymal spermatozoa were incubated for
      4 h at 37 degrees C under 5% CO(2) in air in either the basic medium containing
      rHA, one of the two BSA preparations or no protein, and then cultured in the same
      medium with ovulated oocytes for another 4 h. The experiment was replicated five
      times. RESULTS: Spermatozoa incubated in protein-free medium fertilized only one
      oocyte (2% of total), significantly less than any of the other three treatment
      conditions (P < 0.01); spermatozoa incubated in medium containing rHA or BSA
      fertilized 86-93% of oocytes. There were no differences between the three albumin
      containing treatment groups. CONCLUSION: rHA is equivalent to commercial serum
      albumin preparations in its ability to support sperm capacitation and
      fertilization in this test system. This finding has considerable practical
      implications for human IVF and may also help efforts to elucidate the mechanism
      of sperm capacitation.

PMID- 12525451
TI  - The radiosensitivity of the human oocyte.
AB  - BACKGROUND: We determined the best model available for natural follicle decline
      in healthy women and used this to calculate the radiosensitivity of the human
      oocyte. METHODS: Ovarian failure was diagnosed in six patients with a median age
      of 13.2 years (range 12.5-16.0) who were treated with total body irradiation
      (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of
      radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This
      estimate is an oversimplification, because decay represents an instantaneous rate
      of temporal change based upon the remaining population pool, expressed as a
      differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value
      y(0) = 701 200. RESULTS: Solving the differential equation, we have estimated the
      number of follicles left after irradiation given as sol(51 - s + r), where r
      equals age at treatment, s equals age at diagnosis of ovarian failure, and 51
      years is the average age of menopause. The surviving fraction of oocytes as a
      percentage is 100 times this value divided by sol(r). The mean surviving fraction
      for the six cases is 0.66%. We obtain a function, g(z), which decreases in value
      from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) =
      10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving
      g(z) = 50 gives an LD(50) of 1.99. CONCLUSIONS: Based on new data and a revised
      mathematical model of natural oocyte decline, we have determined the surviving
      fraction of oocytes following irradiation and estimate the LD(50) of the human
      oocyte to be <2 Gy.

PMID- 12525452
TI  - Physiology of meiosis-activating sterol: endogenous formation and mode of action.
AB  - BACKGROUND: In the context of mammalian oocyte maturation, it has been suggested
      that intermediates of cholesterol biosynthesis may represent the physiological
      signal that instructs the oocyte to reinitiate meiosis. METHODS: Endogenous
      levels of follicular fluid meiosis-activating sterol (FF-MAS) were monitored in
      rabbit ovarian tissue, and the influence of exogenous gonadotrophins on sterol
      formation was assessed. The involvement of cAMP in FF-MAS-induced versus
      spontaneous oocyte maturation in vitro in mice was also investigated, as was the
      direct microinjection of FF-MAS into mouse oocytes. RESULTS: Levels of FF-MAS in
      rabbit ovaries were significantly elevated 1 h after hCG/LH induction and
      remained so for 4 and 12 h after induction. In naked oocytes undergoing
      spontaneous maturation, a significant decrease in cAMP was detected after 30 min
      of culture. However, FF-MAS-mediated induction of oocyte maturation in
      hypoxanthine-arrested naked oocytes was not associated with any detectable
      decrease in intracellular cAMP levels. Microinjected FF-MAS failed to induce any
      noticeable meiosis. CONCLUSIONS: A rapid increase in FF-MAS level occurred in
      vivo in the rabbit ovary in response to LH, and clear differences were seen in
      the cAMP pattern during spontaneous and induced oocyte maturation in mice.

PMID- 12525453
TI  - Retinoic acid decreases the viability of mouse blastocysts in vitro.
AB  - BACKGROUND: This study was designed to examine the cytotoxic effect of retinoic
      acid on the blastocyst stage of mouse embryos and on subsequent early
      postimplantation embryo development in vitro. METHODS AND RESULTS: Mouse
      blastocysts were exposed for 24 h to doses of 0, 0.1 micromol/l and 10 micromol/l
      all-trans retinoic acid and observed for their capacity to implant and develop
      during the early postimplantation period in vitro. When retinoic acid-pretreated
      blastocysts were allowed to implant in vitro, significantly fewer embryos were
      able to reach a later stage of embryo development. Compared with the findings for
      the control blastocysts, exposure to retinoic acid resulted in a significant
      reduction in the average number of total cells in blastocysts and the
      trophectoderm/inner cell mass lineage. The effect was associated with a
      significant increase in the frequency of cells identified as being engaged in
      apoptosis by means of the terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labelling and Annexin V techniques. CONCLUSIONS: This is the first
      evidence that retinoic acid induces cell death (apoptosis) and inhibits cell
      proliferation in mouse blastocysts. This results in the retardation of early
      postimplantation blastocyst development and subsequent blastocyst death.

PMID- 12525454
TI  - Pregnancy outcome following transfer of human blastocysts vitrified on electron
      microscopy grids after induced collapse of the blastocoele.
AB  - BACKGROUND: The purpose of this study was to examine the effects on blastocyst
      survival and subsequent pregnancy rate of 'artificial shrinkage' (i.e. induced
      collapse of the blastocoele) before vitrification of human blastocysts. METHODS:
      After embryo transfer in IVF cycles, surplus embryos that developed to the
      expanded blastocyst stage were cryopreserved. Before vitrification on electron
      microscopy (EM) grids, artificial shrinkage was induced in expanded blastocysts
      using a 29-gauge needle. After thawing, transfers were performed on 25 couples.
      Post-thaw survival rates and clinical outcome after the transfer of vitrified
      blastocysts were examined. RESULTS: Of 90 expanded blastocysts vitrified from 25
      patients, 81 survived (90.0%) and 40 of them were hatched (49.4%) at the time of
      transfer. The implantation rate was 29.0% (20/69), and the pregnancy rate was
      48.0% (12/25). Nine patients delivered 15 infants, two pregnancies are ongoing
      and one ended in miscarriage. CONCLUSIONS: The results suggest that artificial
      shrinkage is a useful technique for vitrification of expanded blastocysts on EM
      grids.

PMID- 12525455
TI  - Safety of cryopreservation straws for human gametes or embryos: a study with
      human immunodeficiency virus-1 under cryopreservation conditions.
AB  - BACKGROUND: The possibility of assisted reproductive technology (ART) for couples
      carrying viruses, especially HIV-1, necessitates consideration of the safety of
      cryopreserving human gametes or embryos in liquid nitrogen tanks. Following our
      evaluation of the safety of three kinds of straws containing HIV-1 at 37 degrees
      C, we have now examined the HIV-1 imperviousness of the same straws under
      cryopreservation conditions. METHODS: Polyvinyl chloride (PVC), polyethylene
      terephthalate glycol (PETG) and high-security ionomeric resin (IR) straws (24
      each) were tested. Each straw was filled with 100 microl of HIV-1-containing
      supernatant [reverse transcriptase (RT) activity: 15 000 c.p.m./50 microl]. Then
      PVC and PETG straws were sealed ultrasonically only at their free-end, and IR
      straws were thermosoldered at both ends. Each straw was put in a 15 ml Falcon
      tube which was capped and submerged in a liquid-nitrogen tank for 7 days. After
      bleach decontamination or not, the outside of each end of the straw was rinsed
      with RPMI medium (1 ml) before cryopreservation and after thawing. Viral RNA was
      extracted from the medium and then amplified by RT-polymerase chain reaction
      (PCR) followed by nested-PCR using HIV-1 protease-specific primers. RESULTS: HIV
      1 RNA was detected in some PVC and PETG rinse media, probably resulting from
      splashing during ultrasonic sealing, but not in the rinse media of thermosoldered
      IR straws. CONCLUSION: Under cryopreservation conditions, IR straws would appear
      to be safe for HIV-1 storage in ART. For PVC and PETG straws, as highlighted in
      this study, the ultrasonic sealing could be the weak safety link.

PMID- 12525456
TI  - Laparoscopic microsurgical tubal anastomosis with and without robotic assistance.
AB  - BACKGROUND: We previously reported our results with laparoscopic microsurgical
      tubal anastomosis with robotic assistance. The purpose of this study was to
      compare the duration of the procedure and hospitalization, blood loss and
      clinical outcomes for laparoscopic microsurgical tubal anastomosis performed with
      and without robotic assistance. METHODS: This was a retrospective comparative
      case study in an academic tertiary referral centre. Laparoscopic microsurgical
      tubal anastomosis was performed on 10 women with robotic assistance and the
      subsequent 15 patients underwent the procedure without the robot. The length of
      the procedure, estimated blood loss (EBL), time until hospital discharge, tubal
      patency and clinical pregnancy rates were compared. RESULTS: The operative times
      were 2 h longer with robotic assistance (P < 0.001). The increased EBL with the
      use of the robot (70 +/- 68 ml versus 20 +/- 16 ml) was statistically but not
      clinically significant. The robot provided no benefit in patient recovery. Tubal
      patency and clinical pregnancy rates were not significantly different.
      CONCLUSIONS: Robotic assistance increases operative times of laparoscopic tubal
      anastomosis without an appreciable improvement in patient recovery or clinical
      outcomes.

PMID- 12525457
TI  - Effects of L-arginine and sodium nitroprusside on the spontaneous contractility
      of human non-pregnant uterus.
AB  - BACKGROUND: The aim of this study was to investigate, in isolated human non
      gravid myometrium, the involvement of the cyclic guanosine monophosphate (cGMP)
      pathway in nitric oxide (NO) induced relaxation. METHODS: Strips of human
      myometrium from hysterectomized women were suspended in organ baths for recording
      of isometric tension. Cumulative concentration-response curves for L-arginine and
      sodium nitroprusside were performed in the presence of methylene blue (10
      micromol/l) or vehicle (control). The effect of increasing concentrations of 8
      bromo-cGMP on uterine spontaneous contraction was also studied. RESULTS: L
      arginine and sodium nitroprusside induced a concentration-dependent decrease in
      the amplitude of the myometrial spontaneous contractions. Pre-treatment with
      methylene blue enhanced the inhibitory effect of L-arginine and sodium
      nitroprusside on myometrial spontaneous contractions. In addition, 8-bromo-cGMP
      had no effect on spontaneous contractions in human myometrium. CONCLUSIONS: These
      data provide evidence that L-arginine and sodium nitroprusside inhibit the
      spontaneous contractions of the non-pregnant human uterus through a cGMP
      independent pathway.

PMID- 12525458
TI  - Expression of erythropoietin and erythropoietin receptor in peritoneal
      endometriosis.
AB  - BACKGROUND: Recent studies have indicated new physiological roles for
      erythropoietin (Epo) unrelated to erythropoiesis. We previously demonstrated that
      the Epo concentrations in peritoneal fluid from patients with stage I
      endometriosis were significantly higher than those with stages II, III and IV of
      the disease. Therefore, we hypothesized that Epo may play a role in the
      pathogenesis of endometriosis, particularly during the early stages of the
      disease. METHOD: We investigated the localization of Epo and the Epo receptor
      (Epo-R) in peritoneal endometriosis and eutopic endometrium, using
      immunohistochemistry. RESULTS: We detected Epo and Epo-R localized within
      glandular epithelial cells in both peritoneal endometriosis and eutopic
      endometrium. There was no significant difference in Epo expression between red
      and black peritoneal lesions, whereas Epo-R expression was significantly lower in
      black peritoneal lesions when compared to red lesions. Epo and Epo-R expression
      levels within red peritoneal lesions were comparable to those of eutopic
      endometrium from patients with endometriosis. CONCLUSION: The present findings
      suggest that Epo may play a role in the pathophysiology of endometriosis.

PMID- 12525459
TI  - Anatomical distribution of deeply infiltrating endometriosis: surgical
      implications and proposition for a classification.
AB  - BACKGROUND: Deeply infiltrating endometriosis (DIE) is recognized as a specific
      entity responsible for pain. The distribution of locations and their contribution
      to surgical management has not been previously studied. METHODS: Medical,
      operative and pathological reports of 241 consecutive patients with
      histologically proven DIE were analysed. DIE lesions were classified as: (i).
      bladder, defined as infiltration of the muscularis propria; (ii). uterosacral
      ligaments (USL), as DIE of the USL alone; (iii). vagina, as DIE of the anterior
      rectovaginal pouch, the posterior vaginal fornix and the retroperitoneal area in
      between, and (iv). intestine, as DIE of the muscularis propria. RESULTS: A total
      of 241 patients presented 344 DIE lesions: USL (69.2%; 238); vaginal (14.5%; 50);
      bladder (6.4%; 22); intestinal (9.9%; 34). The proportion of isolated lesions
      differed significantly according to the DIE location: 83.2% (198) for USL DIE;
      56.0% (28) for vaginal DIE; 59.0% (13) for bladder DIE; 29.4% (10) for intestinal
      DIE (P < 0.0001). The total number of DIE lesions varied significantly according
      to the location (P < 0.0001). In 39.1% of cases (9/23) intestinal lesions were
      multifocal. Only 20.6% (seven cases) of intestinal DIE were isolated and
      unifocal. CONCLUSIONS: Multifocality must be considered during the pre-operative
      work-up and surgical treatment of DIE. We propose a surgical classification based
      on the locations of DIE. Operative laparoscopy is efficient for bladder, USL and
      vaginal DIE. However, indications for laparotomy still exist, notably for bowel
      lesions.

PMID- 12525460
TI  - A comparative study of the morphology of congenital uterine anomalies in women
      with and without a history of recurrent first trimester miscarriage.
AB  - BACKGROUND: The true impact of congenital uterine anomalies on reproductive
      outcomes is unknown. The aim of this study was to examine differences in the
      morphology of uterine anomalies found in women with and without a history of
      recurrent miscarriage. METHODS: A total of 509 women with a history of
      unexplained recurrent miscarriage and 1976 low risk women were examined for the
      presence of congenital uterine anomalies by three-dimensional ultrasound. The
      anomalies were classified according to the American Fertility Society
      classification. In addition, the size of fundal distortion (F) and the length of
      the remaining uterine cavity (C) were measured to calculate a distortion ratio
      (F/F+C). The findings were compared with the measurements obtained in low risk
      women with an incidental finding of uterine anomaly. RESULTS: In all, 121
      anomalies were detected in the recurrent miscarriage group and 105 in low risk
      women. There was no significant difference in relative frequency of various
      anomalies or depth of fundal distortion between the two groups. However, with
      both arcuate and subseptate uteri, the length of remaining uterine cavity was
      significantly shorter (P < 0.01) and the distortion ratio was significantly
      higher (P < 0.01) in the recurrent miscarriage group. CONCLUSION: The distortion
      of uterine anatomy is more severe in congenital anomalies, which are found in
      women with a history of recurrent first trimester miscarriage.

PMID- 12525461
TI  - Incomplete vaginal expulsion of pyoadenomyoma with sepsis and focal bladder
      necrosis after uterine artery embolization for symptomatic adenomyosis: case
      report.
AB  - The major complications secondary to uterine artery embolization (UAE) are rare.
      We report a case involving a patient who underwent UAE for symptomatic
      adenomyosis, and experienced complications including incomplete vaginal expulsion
      of a large focal pyoadenomyosis, sepsis and focal bladder necrosis. The serial
      changes of uterine echogenicity reflected the intracavity sloughing tissue, and
      cystourethroscopy revealed a focal bladder necrosis. Administration of
      appropriate antibiotics and timely expulsion of the focal pyoadenomyosis
      vaginally resulted in successful preservation of the uterus and spontaneous
      recovery of focal bladder necrosis without surgical intervention. A review of the
      relevant literature was conducted to explore the mechanisms of bladder necrosis
      after UAE, summarize post-embolization intervention and the outcome of vaginally
      expelled myoma, and to discuss the value of UAE for adenomyosis.

PMID- 12525462
TI  - Changes in the incidence of molar pregnancies. A population-based study in Chiba
      Prefecture and Japan between 1974 and 2000.
AB  - BACKGROUND: The aim of this population-based retrospective study was to evaluate
      the trend in the incidence of molar pregnancy. METHODS: Questionnaires about the
      occurrence of hydatidiform mole were mailed to all clinics and hospitals in Chiba
      Prefecture between 1974 and 2000. The diagnosis of hydatidiform mole was based on
      the post-operative morphological and/or pathological findings. Data of live
      births were collected from the annual reports of maternal and child health
      statistics. A total of 3778 women with hydatidiform mole and 1 661 579 women with
      live births were analysed. RESULTS: The incidence of hydatidiform mole per 1000
      live births was constant from 1974 to 1990, while it decreased significantly
      after 1991 (chi(2)-test for trend, P < 0.0001). The incidence of complete mole
      also decreased after 1991 (chi(2)-test for trend, P = 0.0001), though the
      incidence of partial mole remained unchanged. CONCLUSIONS: The incidence of
      hydatidiform mole in Chiba Prefecture has become as low as that in Europe or the
      USA, and it is attributed to the decreasing incidence of complete mole. A number
      of environmental factors that prevent the ovulation of 'empty' oocytes might have
      contributed to the decreasing incidence of complete mole.

PMID- 12525463
TI  - A prospective randomized study to compare the use of repeated doses of vaginal
      with sublingual misoprostol in the management of first trimester silent
      miscarriages.
AB  - BACKGROUND: A randomized controlled trial comparing sublingual with vaginal
      administration of misoprostol for medical management of silent miscarriages.
      METHODS: Eighty women who had silent miscarriages (<13 weeks) were randomized to
      receive 600 micro g of misoprostol every 3 h for a maximum of three doses either
      sublingually or vaginally. RESULTS: The success rates of medical management were
      the same in both groups (87.5%; 95% CI: 74-95%). There were no serious
      complications. The incidence of diarrhoea was higher in the sublingual (70%) than
      the vaginal route (27.5%) (P < 0.005). Other side effects were similar in each
      group, although fatigue was experienced by more women in the sublingual group
      than in the vaginal group (65 versus 40%: P = 0.043). The overall acceptability
      of medical management was good. Most women would choose the medical method if
      they were allowed to choose again and would recommend the method to others.
      CONCLUSION: The current regimen of misoprostol is useful for the management of
      silent miscarriage in terms of complete miscarriage rate and patient
      acceptability. Sublingual misoprostol may offer an alternative for women who do
      not like repeated vaginal administration of the drug.

PMID- 12525464
TI  - Chromosomal abnormalities and embryo development in recurrent miscarriage
      couples.
AB  - BACKGROUND: Chromosomal abnormalities are an important cause of spontaneous
      abortion and recurrent miscarriage (RM). Therefore, we have analysed the
      incidence of chromosomal abnormalities and embryo development in patients with
      RM. METHODS: Preimplantation genetic diagnosis (PGD) was performed on 71 couples
      with RM and 28 couples undergoing PGD for sex-linked diseases (control group).
      Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in-situ
      hybridization. RESULTS: The implantation rate in RM patients was 28% and three
      patients (13%) miscarried. The percentage of abnormal embryos was significantly
      increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%).
      All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles
      yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for
      chromosomes 16 and 22 were significantly higher (P < 0.01) in RM cases. In the RM
      population, euploid embryos reached the blastocyst stage more frequently than
      abnormal embryos (61.7 versus 24.9%; P < 0.0001). CONCLUSIONS: RM is associated
      with a higher incidence of chromosomally abnormal embryos, of which some are able
      to develop to the blastocyst stage. IVF plus PGD is an important step in the
      management of these couples, but the technique has to move towards a full
      chromosome analysis.

PMID- 12525465
TI  - Successful management of a heterotopic Caesarean scar pregnancy: potassium
      chloride injection with preservation of the intrauterine gestation: case report.
AB  - Caesarean scar pregnancy (CSP), in which the pregnancy is located in the scar of
      a previous Caesarean section, is a rare situation that carries a high risk of
      uterine rupture. Improved ultrasound imaging allows early diagnosis of this
      condition, but there is no standard management. We report the first case of CSP
      associated with a normal intrauterine pregnancy. Potassium chloride administered
      under transvaginal ultrasonographic guidance terminated cardiac activity in the
      CSP. The CSP resolved, and a healthy infant was delivered at 36 weeks. When the
      diagnosis is early and the patient asymptomatic, surgery can be avoided, the CSP
      can be terminated selectively and the intrauterine pregnancy thereby preserved.

PMID- 12525466
TI  - Raloxifene administration in post-menopausal women with osteoporosis: effect of
      different BsmI vitamin D receptor genotypes.
AB  - BACKGROUND: The vitamin D receptor (VDR) gene polymorphism has been considered a
      factor influencing the effectiveness of the anti-osteoporotic treatments. The aim
      of this study was to correlate the effectiveness of raloxifene treatment in post
      menopausal women with osteoporosis to BsmI VDR genotypes. METHODS: Between
      January and August 2000, 75 Italian osteoporotic women were enrolled and treated
      with raloxifene at a dose of 60 mg/day. At entry and after 1 year of treatment,
      lumbar bone mineral density (BMD), serum osteocalcin (OC) and urinary creatinine
      corrected free deoxypyridinoline (DPD) levels were evaluated. DNA was extracted
      from blood and analysed with restriction endonuclease BsmI for VDR gene. RESULTS:
      After treatment, a significant increase in lumbar BMD and a significant reduction
      in serum OC and urinary DPD levels were observed. The percentage of change (mean
      +/- SD) in lumbar BMD, and in serum OC and urinary DPD levels was significantly
      different in homozygous bb (1.58 +/- 0.80, -5.15 +/- 2.36 and -7.71 +/- 2.89 for
      BMD, OC and DPD respectively) in comparison with BB (4.13 +/- 2.26, -13.59 +/-
      4.68 and -15.16 +/- 4.65 for BMD, OC and DPD respectively) BsmI VDR genotypes.
      Heterozygous Bb VDR patients showed an intermediate percentage (mean +/- SD) of
      BMD, serum OC and urinary DPD change (2.49 +/- 1.54, -8.69 +/- 2.60 and -10.52 +/
      2.56 for BMD, OC and DPD respectively) not significantly different in comparison
      with homozygous BB and bb. CONCLUSIONS: In post-menopausal women with
      osteoporosis the effectiveness of raloxifene treatment on bone metabolism seems
      to be controlled by different BsmI VDR genotypes.

PMID- 12525467
TI  - Premature menopause in a multi-ethnic population study of the menopause
      transition.
AB  - BACKGROUND: Premature menopause, also termed premature ovarian failure (POF), is
      characterized by cessation of menstruation before the age of 40 years. Little
      information is available on the general prevalence of POF or on the prevalence by
      ethnic group. There is also a lack of information on the association of POF with
      health indicators. METHODS: A cross-sectional survey of women aged 40-55 years
      was conducted at seven sites in the USA to determine eligibility for a community
      based, multi-ethnic longitudinal study of the peri-menopause (The Study of Women
      Across the Nation, SWAN). Interview data were used to (i). determine the
      prevalence of self-reported POF overall and by ethnic group, and (ii). assess the
      association of POF with selected self-reported variables related to health. Cases
      of POF included only women with no discernible cause for POF. RESULTS: POF was
      reported by 1.1% (126/11 652) of women. By ethnicity, 1.0% (95% CI, 0.7-1.4) of
      Caucasian, 1.4% (95% CI, 1.0-2.1) of African American, 1.4% (95% CI, 0.8-2.5) of
      Hispanic, 0.5% (95% CI, 0.1-1.9) of Chinese and 0.1% (95% CI, 0.02-1.1) of
      Japanese women experienced POF. The differences in frequency across ethnic groups
      were statistically significant (P = 0.01). Only Caucasian, African American and
      Hispanic women were included in further analyses since too few Asian women had
      POF. In a multivariate model, POF was independently associated with osteoporosis,
      female hormone use (excluding oral contraceptives), higher body mass index (BMI)
      and current smoking after adjustment for education level, ability to pay for
      basics, site and age at interview. In Caucasian women, use of female hormones,
      osteoporosis, severe disability and smoking were significantly associated with
      POF. In contrast, POF in African American women was associated with higher BMI
      and female hormone use, but not osteoporosis. CONCLUSIONS: The prevalence of POF
      appears to vary by ethnicity. Health factors associated with POF also vary by
      ethnicity but because of the cross-sectional study design, it is not possible to
      determine cause and effect relationships. Health risks of POF would benefit from
      further study.

PMID- 12525468
TI  - Changes in twinning rate: Italy 1950-1996.
AB  - BACKGROUND: In the wide-ranging debate about the potential monitors of population
      fertility, twinning rate has been considered a candidate. In the developed
      countries, a decline in spontaneous twinning rate began around 1950 and continued
      until the late 1970s. The decrease in mean maternal age at delivery and the
      number of children per family have been considered as possible reasons for the
      decrease. The rise in twinning rates, which began in the 1980s, is probably due
      to the spread of assisted reproduction, at least for older mothers. METHODS: The
      temporal trend in twinning rate and the relationship with maternal age at
      delivery and birth order in the Italian population were analysed. RESULTS: The
      recent increase in twinning rate can be mainly attributed to the recourse to
      assisted reproduction techniques, as demonstrated by the twinning frequency among
      older primiparae. The twinning rate recently observed in young mothers
      approximates to the value of the 1950s, which is assumed to represent a 'natural'
      fertility condition. CONCLUSIONS: On the assumption that twinning is an indicator
      of fertility, and hence of population fitness, the present data seem to suggest
      that natural fertility has been slightly increasing in the Italian population.

PMID- 12525469
TI  - Recruitment and motivation of semen providers in Sweden.
AB  - BACKGROUND: Legislation in Sweden requires that semen providers are prepared to
      be identified to offspring (at maturity) should this be requested. This study
      presents views of semen providers in Sweden regarding factors associated with
      their recruitment and motivation. METHODS: All semen providers (n = 30) in two
      clinics in different parts of Sweden participated in a questionnaire survey and
      both quantitative and qualitative data are reported. RESULTS: While there were
      some important demographic differences between the two clinic populations, there
      was total agreement that the desire to assist infertile couples was the sole or
      main motivating factor in becoming a semen provider. Monetary reward was not
      reported by respondents to be an important motivator, although at least 50% of
      the providers in both clinics thought that payment should be made and
      reimbursement of expenses was reported as being important. Men responded to both
      advertising and personal experiences or contacts they had with infertile couples.
      The involvement and support of the semen provider's partner was regarded as
      important. CONCLUSIONS: Semen providers can be recruited within a system that
      requires them to be prepared to be identified to offspring in the future. The
      characteristics of such providers vary, but are typified by a strong desire to
      assist infertile couples.

PMID- 12525470
TI  - Caesarean Section and subfertility.

PMID- 12525472
TI  - Any effect of adjuvant low dose prednisolone on follicular development and embryo
      implantation may be masked by the concomitant use of aspirin.

PMID- 12525474
TI  - Oocytes from younger women with increased serum FSH are superior to those from
      older women with hypergonadotrophism.

PMID- 12525476
TI  - IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding protein, is
      released from the IP3 receptor upon IP3 binding to the receptor.
AB  - The inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are IP(3)-gated
      Ca(2+) channels on intracellular Ca(2+) stores. Herein, we report a novel
      protein, termed IRBIT (IP(3)R binding protein released with inositol 1,4,5
      trisphosphate), which interacts with type 1 IP(3)R (IP(3)R1) and was released
      upon IP(3) binding to IP(3)R1. IRBIT was purified from a high salt extract of
      crude rat brain microsomes with IP(3) elution using an affinity column with the
      huge immobilized N-terminal cytoplasmic region of IP(3)R1 (residues 1-2217).
      IRBIT, consisting of 530 amino acids, has a domain homologous to S
      adenosylhomocysteine hydrolase in the C-terminal and in the N-terminal, a 104
      amino acid appendage containing multiple potential phosphorylation sites. In
      vitro binding experiments showed the N-terminal region of IRBIT to be essential
      for interaction, and the IRBIT binding region of IP(3)R1 was mapped to the IP(3)
      binding core. IP(3) dissociated IRBIT from IP(3)R1 with an EC(50) of
      approximately 0.5 microm, i.e. it was 50 times more potent than other inositol
      polyphosphates. Moreover, alkaline phosphatase treatment abolished the
      interaction, suggesting that the interaction was dualistically regulated by IP(3)
      and phosphorylation. Immunohistochemical studies and co-immunoprecipitation
      assays showed the relevance of the interaction in a physiological context. These
      results suggest that IRBIT is released from activated IP(3)R, raising the
      possibility that IRBIT acts as a signaling molecule downstream from IP(3)R.

PMID- 12525477
TI  - Identification of two novel nuclear import sequences on the 5-lipoxygenase
      protein.
AB  - The nuclear import of 5-lipoxygenase modulates its capacity to produce
      leukotrienes from arachidonic acid. However, the molecular determinants of its
      nuclear import are unknown. Recently, we used structural and functional criteria
      to identify a novel import sequence at Arg(518) on human 5-lipoxygenase (Jones,
      S. M., Luo, M., Healy, A. M., Peters-Golden, M., and Brock, T. G. (2002) J. Biol.
      Chem. 277, 38550-38556). However, this analysis also indicated that other import
      sequences must exist. Here, we identify two additional sites, at Arg(112) and
      Lys(158), as nuclear import sequences. Both sites were found to be common to 5
      lipoxygenases from different species but not found on other lipoxygenases. Both
      sites also appeared to be a part of structures that were predominantly random
      loops. Peptide sequences at these sites were sufficient to direct nuclear import
      of green fluorescent protein. Mutation of basic residues in these sites impaired
      nuclear import and combinations of mutations at different sites were additive in
      effect. Mutations in all three sites were required to disable nuclear
      accumulation of 5-lipoxygenase in all cells. Significantly, mutation in these
      sites did not inhibit catalytic function. Taken together, these results indicate
      that nuclear import of 5-lipoxygenase may reflect the combined functional effects
      of three discrete import sequences. Mutation of individual sites can, by itself,
      impair nuclear import, which in turn could impact arachidonic acid metabolism.

PMID- 12525478
TI  - Refined solution structure of a liganded type 2 wheat nonspecific lipid transfer
      protein.
AB  - The refined structure of a wheat type 2 nonspecific lipid transfer protein (ns
      LTP2) liganded with l-alpha-palmitoylphosphatidylglycerol has been determined by
      NMR. The (15)N-labeled protein was produced in Pichia pastoris. Physicochemical
      conditions and ligandation were intensively screened to obtain the best NMR
      spectra quality. This ns-LTP2 is a 67-residue globular protein with a diameter of
      about 30 A. The structure is composed of five helices forming a right superhelix.
      The protein presents an inner cavity, which has been measured at 341 A(3). All of
      the helices display hydrophobic side chains oriented toward the cavity. The
      phospholipid is found in this cavity. Its fatty acid chain is completely inserted
      in the protein, the l-alpha-palmitoylphosphatidylglycerol glycerol moiety being
      located on a positively charged pocket on the surface of the protein. The
      superhelix structure of the protein is coiled around the fatty acid chain. The
      overall structure shows similarities with ns-LTP1. Nevertheless, large three
      dimensional structural discrepancies are observed for the H3 and H4 alpha
      helices, the C-terminal region, and the last turn of the H2 helix. The lipid is
      orthogonal to the orientation observed in ns-LTP1. The volume of the hydrophobic
      cavity appears to be in the same range as the one of ns-LTP1, despite the fact
      that ns-LTP2 is shorter by 24 residues.

PMID- 12525479
TI  - Role of the Ca2+/phosphatidylserine binding region of the C2 domain in the
      translocation of protein kinase Calpha to the plasma membrane.
AB  - Signal transduction via protein kinase C (PKC) is closely regulated by its
      subcellular localization. To map the molecular determinants mediating the C2
      domain-dependent translocation of PKCalpha to the plasma membrane, full-length
      native protein and several point mutants in the Ca(2+)/phosphatidylserine-binding
      site were tagged with green fluorescent protein and transiently expressed in rat
      basophilic leukemia cells (RBL-2H3). Substitution of several aspartate residues
      by asparagine completely abolished Ca(2+)-dependent membrane targeting of
      PKCalpha. Strikingly, these mutations enabled the mutant proteins to translocate
      in a diacylglycerol-dependent manner, suggesting that neutralization of charges
      in the Ca(2+) binding region enables the C1 domain to bind diacylglycerol. In
      addition, it was demonstrated that the protein residues involved in direct
      interactions with acidic phospholipids play differential and pivotal roles in the
      membrane targeting of the enzyme. These findings provide new information on how
      the C2 domain-dependent membrane targeting of PKCalpha occurs in the presence of
      physiological stimuli.

PMID- 12525480
TI  - Close proximity of a cytoplasmic loop of subunit a with c subunits of the ATP
      synthase from Escherichia coli.
AB  - Interactions between subunit a and the c subunits of the Escherichia coli ATP
      synthase are thought to control proton translocation through the F(o) sector. In
      this study cysteine substitution mutagenesis was used to define the cytoplasmic
      ends of the first three transmembrane spans of subunit a, as judged by
      accessibility to 3-N-maleimidyl-propionyl biocytin. The cytoplasmic end of the
      fourth transmembrane span could not be defined in this way because of the limited
      extent of labeling of all residues between 186 and 206. In contrast, most of the
      preceding residues in that region, closer to transmembrane span 3, were labeled
      readily. The proximity of this region to other subunits in F(o) was tested by
      reacting mono-cysteine mutants with a photoactivated cross-linker. Residues 165,
      169, 173, 174, 177, 178, and 182-184 could all be cross-linked to subunit c, but
      no sites were cross-linked to b subunits. Attempts using double mutants of
      subunit a to generate simultaneous cross-links to two different c subunits were
      unsuccessful. These results indicate that the cytoplasmic loop between
      transmembrane spans 3 and 4 of subunit a is in close proximity to at least one c
      subunit. It is likely that the more highly conserved, carboxyl-terminal region of
      this loop has limited surface accessibility due to protein-protein interactions.
      A model is presented for the interaction of subunit a with subunit c, and its
      implications for the mechanism of proton translocation are discussed.

PMID- 12525481
TI  - Sti1 is a non-competitive inhibitor of the Hsp90 ATPase. Binding prevents the N
      terminal dimerization reaction during the atpase cycle.
AB  - The molecular chaperone Hsp90 is known to be involved in the activation of key
      regulatory proteins such as kinases, steroid hormone receptors, and transcription
      factors in an ATP-dependent manner. During the chaperone cycle, Hsp90 has been
      found associated with the partner protein Hop/Sti1, which seems to be required
      for the progression of the cycle. However, little is known about its specific
      function. Here we have investigated the interaction of Sti1 from Saccharomyces
      cerevisiae with Hsp90 and its influence on the ATPase activity. We show that the
      inhibitory mechanism of Sti1 on the ATPase activity of Hsp90 is non-competitive.
      Sti1 binds to the N- and C-terminal part of Hsp90 and prevents the N-terminal
      dimerization reaction that is required for efficient ATP hydrolysis. The first 24
      amino acids of Hsp90, a region shown previously to be important for the
      association of the N-terminal domains and stimulation of ATP hydrolysis, seems to
      be important for this interaction.

PMID- 12525482
TI  - Anti-apoptotic signaling by the interleukin-2 receptor reveals a function for
      cytoplasmic tyrosine residues within the common gamma (gamma c) receptor subunit.
AB  - The interleukin-2 receptor (IL-2R) is composed of one affinity-modulating subunit
      (IL-2Ralpha) and two essential signaling subunits (IL-2Rbeta and gammac).
      Although most known signaling events are mediated through tyrosine residues
      located within IL-2Rbeta, no functions have yet been ascribed to gammac tyrosine
      residues. In this study, we describe a role for gammac tyrosines in anti
      apoptotic signal transduction. We have shown previously that a tyrosine-deficient
      IL-2Rbeta chain paired with wild type gammac stimulated enhancement of bcl-2 mRNA
      in IL-2-dependent T cells, but it was not determined which region of the IL-2R or
      which pathway was activated to direct this signaling response. Here we show that
      up-regulation of Bcl-2 by an IL-2R lacking IL-2Rbeta tyrosine residues leads to
      increased cell survival after cytokine deprivation; strikingly, this survival
      signal does not occur in the absence of gammac tyrosine residues. These gammac
      dependent signals are revealed only in the absence of IL-2Rbeta tyrosines,
      indicating that the IL-2R engages at least two distinct signaling pathways to
      regulate apoptosis and Bcl-2 expression. Mechanistically, the gammac-dependent
      signal requires activation of Janus kinases 1 and 3 and is sensitive to
      wortmannin, implicating phosphatidylinositol 3-kinase. Consistent with
      involvement of phosphatidylinositol 3-kinase, Akt can be activated via tyrosine
      residues on gammac. Thus, gammac mediates an anti-apoptotic signaling pathway
      through Akt which cooperates with signals from its partner chain, IL-2Rbeta.

PMID- 12525483
TI  - A novel functional epitope formed by domains 1 and 4 of the human common beta
      subunit is involved in receptor activation by granulocyte macrophage colony
      stimulating factor and interleukin 5.
AB  - The receptors for human interleukins 3 and 5 and granulocyte macrophage colony
      stimulating factor are composed of ligand-specific alpha-subunits and a common
      beta-subunit (betac), the major signaling entity. The way in which betac
      interacts with ligands in the respective activation complexes has remained poorly
      understood. The recently determined crystal structure of the extracellular domain
      of betac revealed a possible ligand-binding interface composed of domain 1 of one
      chain of the betac dimer and the adjacent domain 4 of the symmetry-related chain.
      We have used site-directed mutagenesis, in conjunction with ligand binding and
      proliferation studies, to demonstrate the critical requirement of the domain 1
      residues, Tyr(15) (A-B loop) and Phe(79) (E-F loop), in high affinity complex
      formation and receptor activation. The novel ligand-receptor interface formed
      between domains 1 and 4 represents the first example of a class I cytokine
      receptor interface to be composed of two noncontiguous fibronectin III domains.

PMID- 12525484
TI  - The role of N and C termini in the antifreeze activity of winter flounder
      (Pleuronectes americanus) antifreeze proteins.
AB  - Antifreeze proteins (AFPs) are found in many marine fish and have been classified
      into five biochemical classes: AFP types I-IV and the antifreeze glycoproteins.
      Type I AFPs are alpha-helical, partially amphipathic, Ala-rich polypeptides. The
      winter flounder (Pleuronectes americanus) produces two type I AFP subclasses, the
      liver-type AFPs (wflAFPs) and the skin-type AFPs (wfsAFPs), that are encoded by
      distinct gene families with different tissue-specific expression. wfsAFPs and
      wflAFPs share a high level of identity even though the wfsAFPs have approximately
      half the activity of the wflAFPs. Synthetic polypeptides based on two
      representative wflAFPs and wfsAFPs were generated to examine the role of the
      termini in antifreeze activity. Through systematic exchange of N and C termini
      between wflAFP-6 and wfsAFP-2, the termini were determined to be the major
      causative agents for the variation in activity levels between the two AFPs.
      Furthermore, the termini of wflAFP-6 possessed greater helix-stabilizing ability
      compared with their wfsAFP-2 counterparts. The observed 50% difference in
      activity between wflAFP-6 and wfsAFP-2 can be divided into approximately 20% for
      differences at each termini and approximately 10% for differences in the core.
      Furthermore, the N terminus was determined to be the most critical component for
      antifreeze activity.

PMID- 12525485
TI  - c-Myc is essential but not sufficient for c-Myb-mediated block of granulocytic
      differentiation.
AB  - The c-myb proto-oncogene plays a central role in hematopoiesis and encodes a
      major translational product of 75 kDa. c-Myb is highly expressed in immature
      hematopoietic cells, and its expression is down-regulated during terminal
      differentiation. Deregulated expression of c-Myb has been shown to block terminal
      differentiation of hematopoietic cells. Here we have studied the mechanism of
      action and the nature of target genes through which c-Myb mediates the block in
      differentiation of 32Dcl3 murine myeloid cells. We show that the ectopic
      overexpression of c-Myb in 32Dcl3 cells results in the overexpression of c-Myc.
      However, enforced expression of c-Myc in 32Dcl3 cells did not alter the normal
      pattern of differentiation. In addition, expression of dominant-negative mutants
      of c-Myc relieved c-Myb-mediated block in differentiation. These results led us
      to conclude that c-myc is a target gene of c-Myb and activation of the c-myc gene
      is a necessary event in Myb-mediated transformation. However, c-Myc expression
      alone is inadequate to elicit the phenotypic effects seen with Myb-mediated block
      in differentiation of myeloid cells, suggesting that activation of additional
      transcriptional targets by c-Myb plays a critical role in this process.

PMID- 12525486
TI  - Glucocorticoid down-regulation of RhoA is required for the steroid-induced
      organization of the junctional complex and tight junction formation in rat
      mammary epithelial tumor cells.
AB  - In Con8 mammary epithelial tumor cells, we have documented previously that the
      synthetic glucocorticoid dexamethasone induces the reorganization of the tight
      junction and adherens junction (apical junction) and stimulates the monolayer
      transepithelial electrical resistance (TER), which is a reliable in vitro
      measurement of tight junction sealing. Western blots demonstrated that
      dexamethasone treatment down-regulated the level of the RhoA small GTPase prior
      to the stimulation of the monolayer TER. To test the role of RhoA in the steroid
      regulation of apical junction dynamics functionally, RhoA levels were altered in
      Con8 cells by transfection of either constitutively active (RhoA.V14) or dominant
      negative (RhoA.DN19) forms of RhoA. Ectopic expression of constitutively active
      RhoA disrupted the dexamethasone-stimulated localization of zonula occludens-1
      and beta-catenin to sites of cell-cell contact, inhibited tight junction sealing,
      and prevented the complete formation of the F-actin ring structure at the apical
      side of the cell monolayer. In a complementary manner, dominant negative RhoA
      caused a precocious organization of the tight junction, adherens junction, and
      the F-actin rings in the absence of steroid, whereas the monolayer TER remained
      glucocorticoid-responsive. Taken together, our results demonstrate that the
      glucocorticoid down-regulation of RhoA is a required step in the steroid
      signaling pathway which controls the organization of the apical junctional
      complex and the actin cytoskeleton in mammary epithelial cells.

PMID- 12525487
TI  - Deamination of 5-methylcytosines within cyclobutane pyrimidine dimers is an
      important component of UVB mutagenesis.
AB  - UVB mutagenesis is characterized by an abundance of C --> T and 5-methylcytosine 
      -> T transitions at dipyrimidine sequences. It is not known how these mutations
      might arise. One hypothesis is that UV-induced mutations occur only after
      deamination of the cytosine or 5-methylcytosine within the pyrimidine dimer. It
      is not clear how methylation of cytosines at the 5-position influences
      deamination and how this affects mutagenesis. We have now conducted experiments
      with a CpG-methylated supF shuttle vector that was irradiated with UVB and then
      incubated at 37 degrees C to allow time for deamination before passage through a
      human cell line to establish mutations. This led to a significantly increased
      frequency of CC --> TT mutations and of transition mutations at 5'-PymCG-3'
      sequences. A spectrum of deaminated cis-syn cyclobutane pyrimidine dimers in the
      supF gene was determined using the mismatch glycosylase activities of MBD4
      protein in combination with ligation-mediated PCR. Methylation at the C-5
      position promoted the deamination of cytosines within cis-syn cyclobutane
      pyrimidine dimers, and these two events combined led to a significantly increased
      frequency of UVB-induced transition mutations at 5'-PymCG-3' sequences. Under
      these conditions, the majority of all supF mutations were transition mutations at
      5'-PymCG-3', and they clustered at several mutational hot spots. Exactly these
      types of mutations are frequently observed in the p53 gene of nonmelanoma skin
      tumors. This particular mutagenic pathway may become prevalent under conditions
      of inefficient DNA repair and slow proliferation of cells in the human epidermis.

PMID- 12525488
TI  - Mapping the Galpha13 binding interface of the rgRGS domain of p115RhoGEF.
AB  - Structural requirements for function of the Rho GEF (guanine nucleotide exchange
      factor) regulator of G protein signaling (rgRGS) domains of p115RhoGEF and
      homologous exchange factors differ from those of the classical RGS domains. An
      extensive mutagenesis analysis of the p115RhoGEF rgRGS domain was undertaken to
      determine its functional interface with the Galpha(13) subunit. Results indicate
      that there is global resemblance between the interaction surface of the rgRGS
      domain with Galpha(13) and the interactions of RGS4 and RGS9 with their Galpha
      substrates. However, there are distinct differences in the distribution of
      functionally critical residues between these structurally similar surfaces and an
      additional essential requirement for a cluster of negatively charged residues at
      the N terminus of rgRGS. Lack of sequence conservation within the N terminus may
      also explain the lack of GTPase-activating protein (GAP) activity in a subset of
      the rgRGS domains. For all mutations, loss of functional GAP activity is
      paralleled by decreases in binding to Galpha(13). The same mutations, when placed
      in the context of the p115RhoGEF molecule, produce deficiencies in GAP activity
      as observed with the rgRGS domain alone but show no attenuation of the regulation
      of Rho exchange activity by Galpha(13). This suggests that the rgRGS domain may
      serve a structural or allosteric role in the regulation of the nucleotide
      exchange activity of p115RhoGEF on Rho by Galpha(13).

PMID- 12525489
TI  - The comparative role of activator protein 1 and Smad factors in the regulation of
      Timp-1 and MMP-1 gene expression by transforming growth factor-beta 1.
AB  - The balance between matrix metalloproteinases (MMPs) and their inhibitors, the
      tissue inhibitors of metalloproteinases (TIMPs), is pivotal in the remodeling of
      extracellular matrix. TGF-beta has profound effects on extracellular matrix
      homeostasis, in part via its ability to alter this balance at the level of gene
      expression. The intracellular signaling pathways by which TGF-beta mediates its
      actions include the Smad pathway, specific to the TGF-beta superfamily, but also,
      for example, mitogen-activated protein kinase pathways; furthermore, cross-talk
      between the Smads and other signaling pathways modifies the TGF-beta response.
      The reciprocal effect of TGF-beta on the expression of Timp-1 and MMP-1 supports
      its role in matrix anabolism, yet the mechanisms by which TGF-beta induces Timp-1
      and represses induced MMP-1 have remained opaque. Here, we (i) investigate the
      mechanism(s) by which TGF-beta1 induces expression of the Timp-1 gene and (ii)
      compare this with TGF-beta1 repression of phorbol ester-induced MMP-1 expression.
      We report that the promoter-proximal activator protein 1 (AP1) site is essential
      for the response of both Timp-1 and MMP-1 to TGF-beta (induction and repression,
      respectively). c-Fos, JunD, and c-Jun are essential for the induction of Timp-1
      gene expression by TGF-beta1, but these AP1 factors transactivate equally well
      from both Timp-1 and MMP-1 AP1 sites. Smad-containing complexes do not interact
      with the Timp-1 AP1 site, and overexpression of Smads does not substitute or
      potentiate the induction of the gene by TGF-beta1; furthermore, Timp-1 is still
      induced by TGF-beta1 in Smad knockout cell lines, although to varying extents. In
      contrast, Smads do interact with the MMP-1 AP1 site and mediate repression of
      induced MMP-1 gene expression by TGF-beta1.

PMID- 12525490
TI  - A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal
      transduction by saturated fatty acids.
AB  - Multiple studies suggest that lipid oversupply to skeletal muscle contributes to
      the development of insulin resistance, perhaps by promoting the accumulation of
      lipid metabolites capable of inhibiting signal transduction. Herein we
      demonstrate that exposing muscle cells to particular saturated free fatty acids
      (FFAs), but not mono-unsaturated FFAs, inhibits insulin stimulation of
      Akt/protein kinase B, a serine/threonine kinase that is a central mediator of
      insulin-stimulated anabolic metabolism. These saturated FFAs concomitantly
      induced the accumulation of ceramide and diacylglycerol, two products of fatty
      acyl-CoA that have been shown to accumulate in insulin-resistant tissues and to
      inhibit early steps in insulin signaling. Preventing de novo ceramide synthesis
      negated the antagonistic effect of saturated FFAs toward Akt/protein kinase B.
      Moreover, inducing ceramide buildup recapitulated and augmented the inhibitory
      effect of saturated FFAs. By contrast, diacylglycerol proved dispensable for
      these FFA effects. Collectively these results identify ceramide as a necessary
      and sufficient intermediate linking saturated fats to the inhibition of insulin
      signaling.

PMID- 12525491
TI  - A new member of plant CS-lyases. A cystine lyase from Arabidopsis thaliana.
AB  - Cystine lyases catalyze the breakdown of l-cystine to thiocysteine, pyruvate, and
      ammonia. Until now there are no reports of the identification of a plant cystine
      lyase at a molecular level, and it is not clear what biological role this class
      of enzymes have in plants. A cystine lyase was isolated from Brassica oleracea
      (L.), and partial amino acid sequencing allowed the corresponding full-length
      cDNA (BOCL3) to be cloned. The deduced amino acid sequence of BOCL3 showed
      highest homology to the deduced amino acid sequences of several Arabidopsis
      thaliana genes annotated as tyrosine aminotransferase-like, including a
      coronatine, jasmonic acid, and salt stress-inducible gene, CORI3 (78.8%
      identity), and the unidentified rooty/superroot1 gene (44.8% identity). A full
      length expressed sequence tag clone of CORI3 was obtained and recombinant CORI3
      was synthesized in Escherichia coli. Isolated recombinant CORI3 catalyzed a
      cystine lyase reaction, but no aminotransferase reactions. The present study
      identifies, for the first time, a cystine lyase from plants at a molecular level
      and redefines the functional assignment of the only functionally identified
      member of a group of A. thaliana genes annotated as tyrosine aminotransferase
      like.

PMID- 12525492
TI  - Generation of highly selective VPAC2 receptor agonists by high throughput
      mutagenesis of vasoactive intestinal peptide and pituitary adenylate cyclase
      activating peptide.
AB  - Pituitary adenylate cyclase-activating peptide (PACAP) has a specific receptor
      PAC1 and shares two receptors VPAC1 and VPAC2 with vasoactive intestinal peptide
      (VIP). VPAC2 activation enhances glucose-induced insulin release while VPAC1
      activation elevates glucose output. To generate a large pool of VPAC2 selective
      agonists for the treatment of type 2 diabetes, structure-activity relationship
      studies were performed on PACAP, VIP, and a VPAC2 selective VIP analog. Chemical
      modifications on this analog that prevent recombinant expression were
      sequentially removed to show that a recombinant peptide would retain VPAC2
      selectivity. An efficient recombinant expression system was then developed to
      produce and screen hundreds of mutant peptides. The 11 mutations found on the VIP
      analog were systematically replaced with VIP or PACAP sequences. Three of these
      mutations, V19A, L27K, and N28K, were sufficient to provide most of the VPAC2
      selectivity. C-terminal extension with the KRY sequence from PACAP38 led to
      potent VPAC2 agonists with improved selectivity (100-1000-fold). Saturation
      mutagenesis at positions 19, 27, 29, and 30 of VIP and charge-scanning
      mutagenesis of PACAP27 generated additional VPAC2 selective agonists. We have
      generated the first set of recombinant VPAC2 selective agonists described, which
      exhibit activity profiles that suggest therapeutic utility in the treatment of
      diabetes.

PMID- 12525493
TI  - Loss of phosphatidylinositol 3-phosphate binding by the C-terminal Tiam-1
      pleckstrin homology domain prevents in vivo Rac1 activation without affecting
      membrane targeting.
AB  - Dbl family guanine nucleotide exchange factors (GEFs) for Rho family small
      GTPases invariably contain a pleckstrin homology (PH) domain that immediately
      follows their Dbl homology (DH) domain. Although the DH domain is responsible for
      GEF activity, the role of the PH domain is less clear. We previously reported
      that PH domains from several Dbl family members bind phosphoinositides with very
      low affinity (K(d) values in the 10 microM range). This suggests that, unlike
      several other PH domains, those from Dbl proteins will not function as
      independent membrane-targeting modules. To determine the functional relevance of
      low affinity phosphoinositide binding, we mutated the corresponding PH domain
      from Tiam-1 to abolish its weak, specific binding to phosphatidylinositol 3
      phosphate. We first confirmed in vitro that phosphoinositide binding by the
      isolated DH/PH domain was impaired by the mutations but that intrinsic GEF
      activity was unaffected. We then introduced the PH domain mutations into full
      length Tiam-1 and found that its ability to activate Rac1 or serum response
      factor in vivo was abolished. Immunofluorescence studies showed that membrane
      targeting of Tiam-1 was essentially unaffected by mutations in the C-terminal PH
      domain. Our studies therefore indicate that low affinity phosphatidylinositol 3
      phosphate binding by the C-terminal PH domain may be critical for in vivo
      regulation and activity of Tiam-1 but that the PH domain exerts its regulatory
      effects without altering membrane targeting. We suggest instead that ligand
      binding to the PH domain induces conformational and/or orientational changes at
      the membrane surface that are required for maximum exchange activity of its
      adjacent DH domain.

PMID- 12525494
TI  - Ser3p (Yer081wp) and Ser33p (Yil074cp) are phosphoglycerate dehydrogenases in
      Saccharomyces cerevisiae.
AB  - Two genes YER081W and YIL074C, renamed SER3 and SER33, respectively, which encode
      phosphoglycerate dehydrogenases in Saccharomyces cerevisiae were identified.
      These dehydrogenases catalyze the first reaction of serine and glycine
      biosynthesis from the glycolytic metabolite 3-phosphoglycerate. Unlike either
      single mutant, the ser3Delta ser33Delta double mutant lacks detectable
      phosphoglycerate dehydrogenase activity and is auxotrophic for serine or glycine
      for growth on glucose media. However, the requirement for the SER-dependent
      "phosphoglycerate pathway" is conditional since the "glyoxylate" route of
      serine/glycine biosynthesis is glucose-repressed. Thus, in cells grown on ethanol
      both expression and activity of all SER-encoded proteins are low, including the
      remaining enzymes of the phosphoglycerate pathway, Ser1p and Ser2p. Moreover the
      available nitrogen source regulates the expression of SER genes. However, for
      only SER33, and not SER3, expression was regulated in relation to the available
      nitrogen source in a coordinated fashion with SER1 and SER2. Based on these mRNA
      data together with data on enzyme activities, Ser33p is likely to be the main
      isoenzyme of the phosphoglycerate pathway during growth on glucose. Moreover,
      since phosphoglycerate dehydrogenase activity requires NAD(+) as cofactor,
      deletion of SER3 and SER33 markedly affected redox metabolism as shown by
      substrate and product analysis.

PMID- 12525495
TI  - Effect of famoxadone on photoinduced electron transfer between the iron-sulfur
      center and cytochrome c1 in the cytochrome bc1 complex.
AB  - Famoxadone is a new cytochrome bc(1) Q(o) site inhibitor that immobilizes the
      iron-sulfur protein (ISP) in the b conformation. The effects of famoxadone on
      electron transfer between the iron-sulfur center (2Fe-2S) and cyt c(1) were
      studied using a ruthenium dimer to photoinitiate the reaction. The rate constant
      for electron transfer in the forward direction from 2Fe-2S to cyt c(1) was found
      to be 16,000 s(-1) in bovine cyt bc(1). Binding famoxadone decreased this rate
      constant to 1,480 s(-1), consistent with a decrease in mobility of the ISP.
      Reverse electron transfer from cyt c(1) to 2Fe-2S was found to be biphasic in
      bovine cyt bc(1) with rate constants of 90,000 and 7,300 s(-1). In the presence
      of famoxadone, reverse electron transfer was monophasic with a rate constant of
      1,420 s(-1). It appears that the rate constants for the release of the oxidized
      and reduced ISP from the b conformation are the same in the presence of
      famoxadone. The effects of famoxadone binding on electron transfer were also
      studied in a series of Rhodobacter sphaeroides cyt bc(1) mutants involving
      residues at the interface between the Rieske protein and cyt c(1) and/or cyt b.

PMID- 12525496
TI  - P-glycoprotein (MDR1) expression in leukemic cells is regulated at two distinct
      steps, mRNA stabilization and translational initiation.
AB  - Multidrug resistance in acute myeloid leukemia is often conferred by
      overexpression of P-glycoprotein, encoded by the MDR1 gene. We have characterized
      the key regulatory steps in the development of multidrug resistance in K562
      myelogenous leukemic cells. Unexpectedly, up-regulation of MDR1 levels was not
      due to transcriptional activation but was achieved at two distinct post
      transcriptional steps, mRNA turnover and translational regulation. The short
      lived (half-life 1 h) MDR1 mRNA of naive cells (not exposed to drugs) was
      stabilized (half-life greater than 10 h) following short-term drug exposure.
      However, this stabilized mRNA was not associated with translating polyribosomes
      and did not direct P-glycoprotein synthesis. Selection for drug resistance, by
      long-term exposure to drug, led to resistant lines in which the translational
      block was overcome such that the stabilized mRNA was translated and P
      glycoprotein expressed. The absence of a correlation between steady-state MDR1
      mRNA and P-glycoprotein levels was not restricted to K562 cells but was found in
      other lymphoid cell lines. These findings have implications for the avoidance or
      reversal of multidrug resistance in the clinic.

PMID- 12525497
TI  - Nitric oxide donors inhibit luciferase expression in a promoter-independent
      fashion.
AB  - Nitric oxide (NO) is an important molecule with diverse bio-messenger functions
      including regulation of gene expression. Transcriptional studies using sensitive
      luciferase reporter systems have suggested that NO inhibits the promoter activity
      of a variety of genes. Here we report that NO donors (sodium nitroprusside, 2',2'
      (hydroxynitrosohydrazono)bis-ethanimine, and (+/-)-(E)-4-ethyl-2-[(Z)
      hydroxyimino]-5-nitro-3-hexen-1-yl-nicotinamide) decrease luciferase activity in
      a promoter-independent fashion in both viral and eukaryotic promoters, with a
      reduction to nearly 50% in the presence of 100 microm NO donor. Addition of an
      SV40 enhancer downstream of the luciferase coding region shifted NO donor
      inhibition to the right, with inhibition at approximately 300 microm. In
      contrast, when studied in a chloramphenicol acetyltransferase reporter, two
      promoters indicating inhibition by NO were unaffected. The decrease in luciferase
      activity was not caused by NO suppression of the luciferase enzyme. Real-time PCR
      data showed that luciferase mRNA half-life decreased by nearly half in the
      presence of NO donor (from 75 to 45 min). The SV40 enhancer prolonged luciferase
      mRNA half-life and somewhat blunted the NO effect. Our data suggest that
      exogenous NO inhibits luciferase activity in a dose-dependent manner through
      decreasing luciferase mRNA stability. Thus, the use of luciferase reporter
      systems to study transcriptional regulation by NO should be attempted with
      caution.

PMID- 12525498
TI  - The nature of the arrestin x receptor complex determines the ultimate fate of the
      internalized receptor.
AB  - The vast majority of G protein-coupled receptors are desensitized by a uniform
      two-step mechanism: phosphorylation of an active receptor followed by arrestin
      binding. The arrestin x receptor complex is then internalized. Internalized
      receptor can be recycled back to the plasma membrane (resensitization) or
      targeted to lysosomes for degradation (down-regulation). The intracellular
      compartment where this choice is made and the molecular mechanisms involved are
      largely unknown. Here we used two arrestin2 mutants that bind with high affinity
      to phosphorylated and unphosphorylated agonist-activated beta 2-adrenergic
      receptor to manipulate the receptor-arrestin interface. We found that mutants
      support rapid internalization of beta 2-adrenergic receptor similar to wild type
      arrestin2. At the same time, phosphorylation-independent arrestin2 mutants
      facilitate receptor recycling and sharply reduce the rate of receptor loss,
      effectively protecting beta 2-adrenergic receptor from down-regulation even after
      very long (up to 24 h) agonist exposure. Phosphorylation-independent arrestin2
      mutants dramatically reduce receptor phosphorylation in response to an agonist
      both in vitro and in cells. Interestingly, co-expression of high levels of beta
      adrenergic receptor kinase restores receptor down-regulation in the presence of
      mutants to the levels observed with wild type arrestin2. Our data suggest that
      unphosphorylated receptor internalized in complex with mutant arrestins recycles
      faster than phosphoreceptor and is less likely to get degraded. Thus, targeted
      manipulation of the characteristics of an arrestin protein that binds to a G
      protein-coupled receptors can dramatically change receptor trafficking and its
      ultimate fate in a cell.

PMID- 12525499
TI  - Insulin-induced up-regulated uncoupling protein-1 expression is mediated by
      insulin receptor substrate 1 through the phosphatidylinositol 3-kinase/Akt
      signaling pathway in fetal brown adipocytes.
AB  - To investigate the role of insulin receptor substrate-1 (IRS-1) and its
      downstream signaling in insulin-induced thermogenic differentiation of brown
      adipocytes, we have reconstituted IRS-1-deficient fetal brown adipocytes (IRS-1(
      /-)) with wild-type IRS-1 (IRS-1(wt)). The lack of IRS-1 resulted in the
      inability of insulin to induce IRS-1-associated phosphatidylinositol 3-kinase (PI
      3-kinase) activity and Akt phosphorylation in IRS-1(-/-) brown adipocytes. In
      addition, these cells showed an impairment in activating alpha-Akt, beta-Akt, and
      gamma-Akt isoforms upon insulin stimulation. Reconstitution of IRS-1(-/-) brown
      adipocytes with IRS-1(wt) restored the IRS-1/PI 3-kinase/Akt signaling pathway.
      Treatment of wild-type brown adipocytes with insulin for 24 h up-regulated
      uncoupling protein-1 (UCP-1) expression and transactivated the UCP-1 promoter;
      this effect was abolished in the absence of IRS-1 or in the presence of an Akt
      inhibitor and further recovered after IRS-1(wt) reconstitution. Neither UCP-2 nor
      UCP-3 was up-regulated by insulin in wild-type and IRS-1-deficient brown
      adipocytes. Insulin stimulated the expression of CCAAT/enhancer-binding protein
      alpha (C/EBPalpha) and its DNA binding activity in wild-type brown adipocytes but
      not in IRS-1(-/-) cells. However, insulin stimulation of both C/EBPalpha
      expression and binding activity was restored after IRS-1(wt) reconstitution of
      deficient cells. Retrovirus-mediated expression of C/EBPalpha and peroxisome
      proliferator-activated receptor gamma in IRS-1(-/-) brown adipocytes up-regulated
      UCP-1 protein content and transactivated UCP-1 promoter regardless of insulin
      stimulation. Both C/EBPalpha and peroxisome proliferator-activated receptor gamma
      reconstituted FAS mRNA expression, but only C/EBPalpha restored insulin
      sensitivity in the absence of IRS-1. Finally, reconstitution of IRS-1(-/-) brown
      adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor
      receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with
      IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1
      expression and transactivated the UCP-1 promoter. These data provide strong
      evidence for an essential role of IRS-1 through the PI 3-kinase/Akt signaling
      pathway inducing UCP-1 gene expression by insulin.

PMID- 12525500
TI  - Guggulsterone is a farnesoid X receptor antagonist in coactivator association
      assays but acts to enhance transcription of bile salt export pump.
AB  - Guggulipid is an extract of the guggul tree Commiphora mukul and has been widely
      used to treat hyperlipidemia in humans. The plant sterol guggulsterone (GS) is
      the active agent in this extract. Recent studies have shown that GS can act as an
      antagonist ligand for farnesoid X receptor (FXR) and decrease expression of bile
      acid-activated genes. Here we show that GS, although an FXR antagonist in
      coactivator association assays, enhances FXR agonist-induced transcription of
      bile salt export pump (BSEP), a major hepatic bile acid transporter. In HepG2
      cells, in the presence of an FXR agonist such as chenodeoxycholate or GW4064, GS
      enhanced endogenous BSEP expression with a maximum induction of 400-500% that
      induced by an FXR agonist alone. This enhancement was also readily observed in
      FXR-dependent BSEP promoter activation using a luciferase reporter construct. In
      addition, GS alone slightly increased BSEP promoter activation in the absence of
      an FXR agonist. Consistent with the results in HepG2, guggulipid treatment in
      Fisher rats increased BSEP mRNA. Interestingly, in these animals expression of
      the orphan nuclear receptor SHP (small heterodimer partner), a known FXR target,
      was also significantly increased, whereas expression of other FXR targets
      including cholesterol 7alpha-hydroxylase (Cyp 7a1), sterol 12alpha-hydroxylase
      (Cyp 8b1), and the intestinal bile acid-binding protein (I-BABP), remained
      unchanged. Thus, we propose that GS is a selective bile acid receptor modulator
      that regulates expression of a subset of FXR targets. Guggulipid treatment in
      rats lowered serum triglyceride and raised serum high density lipoprotein levels.
      Taken together, these data suggest that guggulsterone defines a novel class of
      FXR ligands characterized by antagonist activities in coactivator association
      assays but with the ability to enhance the action of agonists on BSEP expression
      in vivo.

PMID- 12525501
TI  - Rational optimization of a short human P-selectin-binding peptide leads to
      nanomolar affinity antagonists.
AB  - P-selectin plays an important role in the development of various diseases,
      including atherosclerosis and thrombosis. In our laboratory we recently
      identified a number of specific human P-selectin-binding peptides containing a
      Glu-Trp-Val-Asp-Val consensus motif, displaying a low micromolar affinity for P
      selectin (IC(50) = 2 microm). In search of more potent antagonists for P
      selectin, we have optimized the EWVDV pentapeptide core motif via a two-step
      combinatorial chemistry approach. A dedicated library of peptide derivatives was
      generated by introducing seven substituents at the N and C termini of the motif.
      In particular, pentapeptides with gallic acid or 1,3,5-benzenetricarboxylic acid
      substituents at the N terminus proved to be considerably more potent inhibitors
      of P-selectin binding than the parental peptide. After removal of the N-terminal
      glutamic acid from the core sequence, which appeared to be replaceable by a
      carboxamide function without loss of affinity, a second library was synthesized
      to map the chemical moieties within the gallic acid or 1,3,5-benzenetricarboxyl
      acid groups responsible for the enhanced P-selectin binding. Moreover, by varying
      the length and rigidity of the connective spacer, we have further optimized the
      spatial orientation of the N-terminal substituent. The combined use of phage
      display and subsequent combinatorial chemistry led to the design of a number of
      gallic acid- containing peptides with low nanomolar affinity for P-selectin both
      under static and dynamic conditions (IC(50) = 15.4 nm). These small synthetic
      antagonists, which are equally as potent as the natural ligand P-selectin
      glycoprotein ligand-1, are promising leads in anti-atherothrombotic therapy.

PMID- 12525502
TI  - Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis
      inducer Smac/DIABLO.
AB  - Inhibitors of apoptosis (IAPs) are crucial regulators of programmed cell death.
      The mechanism by which IAPs prevent apoptosis has previously been attributed to
      the direct inhibition of caspases. The function of mammalian IAPs is counteracted
      by cell death inducer second mitochondria-derived activator of caspases
      (Smac)/DIABLO during apoptosis. Here we show that cIAP1 and cIAP2 are E3
      ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac. cIAPs
      stimulate Smac ubiquitination both in vivo and in vitro, leading to Smac
      degradation. cIAP1 and cIAP2 associate with overlapping but distinct subsets of
      E2 (ubiquitin carrier protein) ubiquitin-conjugating enzymes. The substrate
      dependent E3 activity of cIAPs is mediated by their RING domains and is dependent
      on the specific interactions between cIAPs and Smac. Similarly, Drosophila IAP1
      also possesses ubiquitin ligase activity that mediates the degradation of the
      Drosophila apoptosis inducers Grim and HID. These results suggest a novel and
      conserved mechanism by which IAPs block apoptosis through the degradation of
      death inducers.

PMID- 12525503
TI  - MAGE-A4 interacts with the liver oncoprotein gankyrin and suppresses its
      tumorigenic activity.
AB  - Hepatocellular carcinoma ranks among the most common malignancies in Southeast
      Asia and South Africa. Although there are many modalities of treatment, the
      recurrence and metastasis rates are high, and the prognosis is unsatisfactory.
      Gankyrin, a recently found oncoprotein, is a promising target for drug therapy
      because it is overexpressed in all studied hepatocellular carcinomas. Gankyrin
      contains six ankyrin repeats and interacts with Rb, Cdk4, and the S6 ATPase of
      the 26 S proteasome. In this study, a yeast two-hybrid screen with gankyrin has
      identified MAGE-A4 as another interacting protein. The interaction, mediated by
      the C-terminal half of MAGE-A4, was reproduced in mammalian cells. The
      interaction was specific to MAGE-A4, because other MAGE family proteins
      structurally similar to MAGE-A4, i.e. MAGE-A1, MAGE-A2, and MAGE-A12, did not
      bind to gankyrin. MAGE-A4 partially suppressed both anchorage-independent growth
      in vitro and tumor formation in athymic mice of gankyrin-overexpressing cells.
      The ability of mutant MAGE-A4 to interact with gankyrin correlated with the
      ability to suppress the anchorage-independent growth. These results demonstrate
      that MAGE-A4 binds to gankyrin and suppresses its oncogenic activity. So far, the
      major focus of studies on the MAGE proteins has been on their potential for
      cancer immunotherapy. Our results may also shed light on novel functions for MAGE
      A proteins.

PMID- 12525504
TI  - Hierarchy of polymorphic variation and desensitization permutations relative to
      beta 1- and beta 2-adrenergic receptor signaling.
AB  - Agonist-promoted desensitization of G-protein-coupled receptors results in
      partial uncoupling of receptor from cognate G-protein, a process that provides
      for rapid adaptation to the signaling environment. This property plays important
      roles in physiologic and pathologic processes as well as therapeutic efficacy.
      However, coupling is also influenced by polymorphic variation, but the relative
      impact of these two mechanisms on signal transduction is not known. To determine
      this we utilized recombinant cells expressing the human beta(1)-adrenergic
      receptor (beta(1)AR) or a gain-of-function polymorphic variant (beta(1)AR
      Arg(389)), and the beta(2)-adrenergic receptor (beta(2)AR) or a loss-of-function
      polymorphic receptor (beta(2)AR-Ile(164)). Adenylyl cyclase activities were
      determined with multiple permutations of the possible states of the receptor:
      genotype, basal, or agonist stimulated and with or without agonist pre-exposure.
      For the beta(1)AR, the enhanced function of the Arg(389) receptor underwent less
      agonist-promoted desensitization compared with its allelic counterpart. Indeed,
      the effect of polymorphic variation on absolute adenylyl cyclase activities was
      such that desensitized beta(1)AR-Arg(389) signaling was equivalent to non
      desensitized wild-type beta(1)AR; that is, the genetic component had as much
      impact as desensitization on receptor coupling. In contrast, the enhanced
      signaling of wild-type beta(2)AR underwent less desensitization compared with
      beta(2)AR-Ile(164), thus the heterogeneity in absolute signaling was markedly
      broadened by this polymorphism. Inverse agonist function was not affected by
      polymorphisms of either subtype. A general model is proposed whereby up to 10
      levels of signaling by G-protein-coupled receptors can be present based on the
      influences of desensitization and genetic variation on coupling.

PMID- 12525505
TI  - Blue light perception in plants. Detection and characterization of a light
      induced neutral flavin radical in a C450A mutant of phototropin.
AB  - The LOV2 domain of Avena sativa phototropin and its C450A mutant were expressed
      as recombinant fusion proteins and were examined by optical spectroscopy,
      electron paramagnetic resonance, and electron-nuclear double resonance. Upon
      irradiation (420-480 nm), the LOV2 C450A mutant protein gave an optical
      absorption spectrum characteristic of a flavin radical even in the absence of
      exogenous electron donors, thus demonstrating that the flavin mononucleotide
      (FMN) cofactor in its photogenerated triplet state is a potent oxidant for redox
      active amino acid residues within the LOV2 domain. The FMN radical in the LOV2
      C450A mutant is N(5)-protonated, suggesting that the local pH close to the FMN is
      acidic enough so that the cysteine residue in the wild-type protein is likely to
      be also protonated. An electron paramagnetic resonance analysis of the
      photogenerated FMN radical gave information on the geometrical and electronic
      structure and the environment of the FMN cofactor. The experimentally determined
      hyperfine couplings of the FMN radical point to a highly restricted
      delocalization of the unpaired electron spin in the isoalloxazine moiety. In the
      light of these results a possible radical-pair mechanism for the formation of the
      FMN-C(4a)-cysteinyl adduct in LOV domains is discussed.

PMID- 12525506
TI  - Toward optimal central nervous system-directed treatment in childhood acute
      lymphoblastic leukemia.

PMID- 12525507
TI  - Horseshoes, hand grenades, and body-surface area-based dosing: aiming for a
      target.

PMID- 12525508
TI  - Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic
      leukemia: significance of low leukocyte counts with blasts or traumatic lumbar
      puncture.
AB  - PURPOSE: To determine the significance of leukemic blasts or traumatic lumbar
      puncture (TLP) in diagnostic CSF of children enrolled in the Berlin-Frankfurt
      Munster (BFM) Acute Lymphoblastic Leukemia-BFM-95 trial. PATIENTS AND METHODS: A
      total of 2,021 patients were retrospectively evaluated according to initial
      central nervous system (CNS) status. Patients were classified as follows: CNS1
      (CNS negative, n = 1,605), CNS2 (< or = 5 WBC/ micro L CSF with blasts, n = 103),
      CNS3 (CNS positive, n = 58), TLP+ (TLP with blasts, n = 135), or TLP- (TLP
      without blasts, n = 111). Patients with CNS2 and TLP+ status were eligible for
      two additional doses of intrathecal (IT) methotrexate (MTX). CNS3 patients
      received additional IT MTX and cranial irradiation (18 Gy). RESULTS: CNS2, CNS3,
      and TLP+ groups contained a higher percentage of patients with unfavorable
      characteristics. Cox regression analysis identified TLP+ and CNS3 status as
      prognostically significant (CNS3): risk ratio (RR) = 2.3; 95% confidence interval
      [CI], 1.4 to 3.6; P =.0005; TLP+: RR = 1.5; 95% CI, 1.02 to 2.2; P =.04. Overall
      5-year event-free survival (EFS) is 79%, for CNS1 it is 80%, and for TLP- it is
      83%. CNS2 patients have an EFS of 80%, but the cumulative incidence of relapses
      with CNS involvement is higher compared with CNS1 patients (0.10 v 0.04). TLP+
      patients have a significantly reduced EFS (73%, P =.003) because of an increased
      incidence of CNS relapses. CNS3 patients suffer from more systemic and CNS
      relapses (EFS 50%). CONCLUSION: CNS2 patients have the same prognosis as patients
      with CNS1 status, whereas the EFS of TLP+ patients is inferior to CNS1 but
      superior to CNS3 patients (P =.001). Both subgroups may have benefitted from
      additional IT MTX.

PMID- 12525509
TI  - Smoking among participants in the childhood cancer survivors cohort: the
      Partnership for Health Study.
AB  - PURPOSE: This article describes baseline data collection and the intervention
      design of Partnership for Health, a smoking cessation intervention for smokers in
      the Childhood Cancer Survivors Study. The purpose of this article is to evaluate
      demographic, psychosocial, and cancer-related factors that are associated with
      smoking behavior and mediators of smoking cessation. PATIENTS AND METHODS: This
      study includes 796 smokers from the Childhood Cancer Survivors Study database who
      were diagnosed with cancer before the age of 21, had survived at least 5 years,
      and were at least 18 years of age at the time of the baseline survey. Correlates
      of smoking behaviors included smoking rate, number of recent quit attempts, and
      nicotine dependence; two key mediators of smoking cessation, readiness to quit
      smoking and self-efficacy, were also assessed. RESULTS: Participants smoked, on
      average, 14 cigarettes/day; 53.2% were nicotine dependent, and 58% had made at
      least one quit attempt in the past year. Smoking behaviors were primarily
      associated with demographic variables; mediators of cessation were primarily
      associated with age at cancer diagnosis and perceived vulnerability to smoking
      related illnesses. Severity of psychologic symptoms was associated with increased
      smoking rate, high nicotine dependence, and low self-efficacy. Support for
      quitting was related to smoking rate, number of quit attempts, readiness to quit
      smoking, and self-efficacy. CONCLUSION: These findings indicate that many cancer
      survivors who smoke are receptive to smoking cessation interventions. Factors
      related to mediators of smoking cessation might be particularly good targets for
      intervention.

PMID- 12525510
TI  - Randomized cross-over evaluation of body-surface area-based dosing versus flat
      fixed dosing of paclitaxel.
AB  - PURPOSE: Despite dose calculation using body-surface area (BSA), pharmacokinetics
      of most anticancer drugs show wide interindividual variability. In this study, we
      evaluated the role of BSA in paclitaxel disposition. PATIENTS AND METHODS:
      Paclitaxel pharmacokinetics were prospectively studied in 12 patients that were
      treated in a randomized cross-over design with paclitaxel (3-hour infusion at a 3
      week interval) at 175 mg/m2 in cycle 1 (A) and a flat-fixed dose of 300 mg in
      cycle 2 (B), or vice versa. Blood samples were collected up to 24 hours after
      dosing and analyzed for total and unbound paclitaxel. RESULTS: The area under the
      curves (AUC) of unbound paclitaxel were similar in both dosing groups, with mean
      values +/- SD (A v B) of 1.34 +/- 0.158 versus 1.30 +/- 0.329 microM x h,
      indicating that BSA-based dosing reduced the coefficient of variation by 53.3%.
      Unbound and total paclitaxel clearance was also significantly related to various
      body-size measures, including BSA (R > or = 0.617; P < or =.033), weight (R >or =
      0.621; P < or =.031), and lean-body mass (r > or = 0.630; P < or = .028). We
      hypothesize that this is caused by the association of paclitaxel in the
      circulation with Cremophor EL, the distribution of which is linked to total blood
      volume, and thus to BSA. CONCLUSION: This study indicates that paclitaxel
      disposition is significantly related to BSA. This provides a pharmacokinetic
      rationale for BSA-based dosing of this drug.

PMID- 12525511
TI  - Use of positron emission tomography in pharmacokinetic studies to investigate
      therapeutic advantage in a phase I study of 120-hour intravenous infusion XR5000.
AB  - PURPOSE: XR5000 (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide) is a
      topoisomerase I and II inhibitor. Because the cytotoxicity of XR5000 increases
      markedly with prolonged exposure, we performed a phase I study of weekly XR5000
      by 120-hour continuous infusion over 3 weeks. PATIENTS AND METHODS: Twenty-four
      patients with advanced solid cancer were treated at seven dose levels (700 to
      4,060 mg/m2/120 hrs) for a total of 67 cycles. Three patients underwent positron
      emission tomography (PET) studies at the maximum-tolerated dose (MTD) to evaluate
      normal tissue and tumor carbon-11 radiolabeled XR5000 ([11C]XR5000)
      pharmacokinetics. RESULTS: The dose-limiting toxicity was National Cancer
      Institute Common Toxicity Criteria (version 1) grade 4 chest and abdominal pain
      affecting the single patient receiving 4,060 mg/m2/120 hours, and the MTD was
      3,010 mg/m2/120 hours. Other grade 3-4 toxicities, affecting single patients at
      the MTD, were myelosuppression (grade 4), raised bilirubin, vomiting, and
      somnolence (all grade 3). There was one partial response (adenocarcinoma of
      unknown primary); the remainder had progressive disease. [11C]XR5000 distributed
      well into the three tumors studied by PET. Tumor uptake (maximum concentration or
      area under the concentration versus time curve [AUC]) was less than in normal
      tissue in which the tumors were located. Tumor exposure (AUC; mean +/- SD in
      m2/mL/sec) increased when [(11)C]XR5000 was administered during an infusion of
      XR5000 (0.242 +/- 0.4), compared with [11C]XR5000 given alone (0.209 +/- 0.04; P
      <.05), indicating that tumor drug exposure was not saturated [corrected].
      CONCLUSION: The recommended dose for XR5000 in phase II studies is 3,010
      mg/m2/120 hours. PET studies with 11C-labeled drug were feasible and demonstrated
      in vivo distribution into tumors. Saturation of tumor exposure was not reached at
      the MTD.

PMID- 12525512
TI  - Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg
      antigen: a phase I, pharmacokinetic, and biologic correlative study.
AB  - PURPOSE: To determine the maximum tolerated dose and pharmacokinetics of
      cantuzumab mertansine, an immunoconjugate of the potent maytansine derivative
      (DM1) and the humanized monoclonal antibody (huC242) directed to CanAg,
      intravenously (i.v.) once every 3 weeks and to seek evidence of antitumor
      activity. PATIENTS AND METHODS: Patients with CanAg-expressing solid malignancies
      were treated with escalating doses of cantuzumab mertansine administered i.v.
      every 3 weeks. The pharmacokinetic parameters of cantuzumab mertansine, the
      presence of plasma-shed CanAg, and the development of both human antihuman and
      human anti-DM1 conjugate antibodies also were characterized. RESULTS: Thirty
      seven patients received 110 courses of cantuzumab mertansine at doses ranging
      from 22 to 295 mg/m2. Acute, transient, and reversible elevations of hepatic
      transaminases were the principal toxic effects. Nausea, vomiting, fatigue, and
      diarrhea were common but rarely severe at the highest dose levels. Dose, peak
      concentration, and area under the concentration-time curve correlated with the
      severity of transaminase elevation. The mean (+/- SD) clearance and terminal
      elimination half-life values for cantuzumab mertansine averaged 39.5 (+/-13.1)
      mL/h/m2 and 41.1 (+/-16.1) hours, respectively. Strong expression (3+) of CanAg
      was documented in 68% of patients. Two patients with chemotherapy-refractory
      colorectal carcinoma had minor regressions, and four patients had persistently
      stable disease for more than six courses. CONCLUSION: The recommended dose for
      cantuzumab mertansine is 235 mg/m2 i.v. every 3 weeks. The absence of severe
      hematologic toxic effects, preliminary evidence of cantuzumab mertansine tumor
      localization, and encouraging biologic activity in chemotherapy-refractory
      patients warrant further broad clinical development of this immunoconjugate in
      CanAg-expressing tumors.

PMID- 12525513
TI  - Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin
      in patients with advanced solid tumors.
AB  - PURPOSE: Endostatin is the first endogenous angiogenesis inhibitor to enter
      clinical trials. Laboratory investigations with endostatin have indicated broad
      antitumor activity coupled with remarkably low toxicity. A phase I trial of
      recombinant human endostatin was designed to evaluate toxicity and explore
      biologic effectiveness in patients with refractory solid tumors. PATIENTS AND
      METHODS: Endostatin was administered as a 1-hour intravenous infusion given daily
      for a 28-day cycle. A starting dose of 30 mg/m2 was explored with subsequent dose
      escalations of 60, 100, 150, 225, and 300 mg/m2. Assessment of serum
      pharmacokinetics was performed on all 21 patients. Western blot assay and mass
      spectroscopy were employed to evaluate endostatin metabolism. Circulating levels
      of endogenous proangiogenic growth factors were examined. Tumor and tumor blood
      supply were imaged by dynamic computed tomography (CT), magnetic resonance
      imaging, ultrasound, and positron emission tomography. RESULTS: Endostatin given
      on this schedule was essentially free of significant drug-related toxicity. Two
      transient episodes of grade 1 rash were observed. No clinical responses were
      observed. Endostatin pharmacokinetics were linear with dose, and serum
      concentrations were achieved that are associated with antitumor activity in
      preclinical models. No aggregate effect on circulating proangiogenic growth
      factors were seen, although several patients exhibited persistent declines in
      vascular endothelial growth factor levels while enrolled in the study. A few
      patients demonstrated changes in their dynamic CT scans suggestive of a decline
      in microvessel density, although overall, no consistent effect of endostatin on
      tumor vasculature was seen. CONCLUSION: Endostatin given daily as a 1-hour
      intravenous infusion was well tolerated without dose-limiting toxicity at doses
      up to 300 mg/m2.

PMID- 12525514
TI  - SarCNU, a nitrosourea analog on a day 1, 5, and 9 oral schedule: a phase I and
      pharmacokinetic study in patients with advanced solid tumors.
AB  - PURPOSE: 2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) is a novel
      chloroethylnitrosourea that demonstrates selective cytotoxicity in athymic mice
      bearing human glioma. SarCNU demonstrates selective cytotoxicity in vitro against
      human glioma at least in part because of the selective SarCNU uptake by the
      extraneuronal monoamine transporter. The purpose of this phase I study was to
      determine the maximum-tolerated dose (MTD), the toxicity profile, the
      pharmacokinetics profile, and recommended phase II dose. PATIENTS AND METHODS:
      Forty-three eligible patients with advanced solid tumors were enrolled. SarCNU
      was administered orally on days 1,5, and 9 every 28 days. The dose ranged from 30
      to 1,075 mg/m2. Pharmacokinetic evaluation was done on the first cycle (one dose
      was given intravenously on day 1 or 5 of the first cycle to determine
      bioavailability). RESULTS: Delayed myelosuppression (thrombocytopenia and
      neutropenia occurring 4 to 6 weeks after administration) was the dose-limiting
      toxicity (DLT). Anemia occurred but was mild. Nonhematologic toxicity was
      generally mild, but one patient died with pulmonary toxicity that was probably
      secondary to SarCNU. There were no partial or complete responses, but eight
      patients had stable disease for 19 to 46 weeks. The oral bioavailability of
      SarCNU was 80% +/- 37%. The terminal phase half-life was similar after
      intravenous (58.4 +/- 23.5 minutes) or oral (64.0 +/- 34.8 minutes)
      administration. The total plasma clearance was 20.4 +/- 8.8 L/h/m2, and the
      apparent volume of distribution was 29.9 +/- 17.6 L/m2. The area under the plasma
      concentration-time profile increased proportionally with the dose, and the
      pharmacokinetics seemed to be independent of the route of administration and the
      number of doses. CONCLUSION: SarCNU was well tolerated and the MTD was 1,075
      mg/m2. The recommended starting dose for phase II trials is 860 mg/m2 orally on
      days 1, 5, and 9 every 6 weeks.

PMID- 12525515
TI  - Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes'
      B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant
      Breast and Bowel Project collaborative study.
AB  - PURPOSE: To define the value of thymidylate synthase (TS), Ki-67, and p53 as
      prognostic markers in patients with stage II and III colon carcinoma. PATIENTS
      AND METHODS: We retrospectively analyzed the prognostic value of TS, Ki-67, and
      p53 in 706 patients with Dukes' B (291 patients) or Dukes' C (415 patients) colon
      carcinoma who were treated with either surgery alone (275 patients) or surgery
      plus fluorouracil (FU)-leucovorin chemotherapy (431 patients) in National
      Surgical Adjuvant Breast and Bowel Project (NSABP) protocols C01-C04. All three
      markers were assayed using immunohistochemical techniques. RESULTS: Using 5 years
      of follow-up data, our retrospective analysis demonstrated an association between
      TS intensity (relapse-free survival [RFS]: risk ratio [RR] = 1.46, P =.01;
      overall survival [OS]: RR = 1.54, P =.002), Ki-67 (RFS: RR = 0.76, P =.05; OS: RR
      = 0.62, P =.001), and p53 (RFS: RR = 1.49, P =.01; OS: RR = 1.21, P =.18) for RFS
      and OS. High TS intensity levels and positive p53 staining were associated with a
      worse outcome. Tumors containing a high percentage of Ki-67-positive cells
      enjoyed an improved outcome compared with those patients whose tumors contained
      relatively few positive cells. An interaction with treatment was not identified
      for any of the markers. CONCLUSION: This retrospective investigation demonstrated
      that TS, Ki-67, and p53 staining each had significant prognostic value for
      patients with Dukes' B and C colon carcinoma. However, none of the markers could
      be used to clearly discern groups of individuals who would be predicted to derive
      greater or lesser benefit from the use of adjuvant chemotherapy.

PMID- 12525516
TI  - Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for
      patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and
      associations with chromosomal abnormalities.
AB  - PURPOSE: The purpose of this article is to determine the response rate and
      toxicity of PCV administered before radiation therapy in patients with newly
      diagnosed LGO/LGOA and to explore correlations between response with 1p/19q
      deletions and aberrant p53 expression. BACKGROUND: Despite prolonged survival of
      patients with low-grade oligodendroglioma (LGO) and oligoastrocytoma (LGOA), the
      majority will succumb to progressive disease. Because procarbazine, lomustine
      (CCNU), and vincristine (PCV) is active in patients with recurrent LGO/LGOA, we
      hypothesized that it would be beneficial as primary therapy. METHODS: Adult
      patients with residual tumor on magnetic resonance imaging scan following biopsy
      or subtotal resection of LGO/LGOA received up to six cycles of PCV. Radiation
      therapy (59.4 or 54.0 Gy) began within 10 weeks of completing chemotherapy or
      immediately if there was evidence of tumor progression on PCV. Tumor tissue was
      analyzed by fluorescent in situ hybridization for 1p and 19q deletion and by
      immunohistochemistry for p53 expression. RESULTS: Eight of 28 (29%) and 13 of 25
      (52%) eligible patients demonstrated tumor regression as assessed by the treating
      physician and a blinded central neuroradiology reviewer, respectively.
      Myelosuppression was the predominant toxicity. Loss of 1p and 19q were associated
      with LGO but not LGOA (P =.009), were inversely associated with p53 detection,
      and were not associated with response to PCV (possibly because of the small
      sample size). CONCLUSION: PCV produces tumor regressions in a meaningful
      proportion of patients with LGO/LGOA. Toxicity, especially myelosuppression, is
      significant. Loss of 1p and 19q seems limited to patients with pure LGO and is
      inversely related to p53 alterations.

PMID- 12525517
TI  - Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to
      unfavorable cytogenetics but has no independent prognostic relevance under the
      conditions of intensive induction therapy: results of a multiparameter analysis
      from the German AML Cooperative Group studies.
AB  - PURPOSE: On the basis of cytomorphology according to the French-American-British
      (FAB) classification, we evaluated the prognostic impact of dysplastic features
      and other parameters in de novo acute myeloid leukemia (AML). We also assessed
      the clinical significance of the recently introduced World Health Organization
      (WHO) classification for AML, which proposed dysplasia as a new parameter for
      classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with
      de novo AML, all of whom were diagnosed by central morphologic analysis and
      treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute
      promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo
      demonstrated a better outcome compared with all other FAB subtypes (P <.001); no
      prognostic difference was observed among other FAB subtypes. The presence or
      absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic
      markers, such as age, cytogenetics, presence of Auer rods, and lactate
      dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall
      and event-free survival in univariate analyses (P <.001 for all parameters
      tested). However, in a multivariate analysis, only cytogenetics (unfavorable or
      favorable), age, and high LDH maintained their prognostic impact. Dysplasia was
      not found to be an independent prognostic parameter, but the detection of
      trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our
      results indicate that cytomorphology and classification according to FAB criteria
      are still necessary for the diagnosis of AML but have no relevance for prognosis
      in addition to cytogenetics. Our results suggest that the WHO classification
      should be further developed by using cytogenetics as the main determinant of
      biology. Dysplastic features, in particular, have no additional impact on
      predicting prognosis when cytogenetics are taken into account.

PMID- 12525518
TI  - Prognostic scoring system for primary CNS lymphomas: the International Extranodal
      Lymphoma Study Group experience.
AB  - PURPOSE: To identify survival predictors and to design a prognostic score useful
      for distinguishing risk groups in immunocompetent patients with primary CNS
      lymphomas (PCNSL). PATIENTS AND METHODS: The prognostic role of patient-,
      lymphoma-, and treatment-related variables was analyzed in a multicenter series
      of 378 PCNSL patients treated at 23 cancer centers from five different countries.
      RESULTS: Age more than 60 years, performance status (PS) more than 1, elevated
      lactate dehydrogenase (LDH) serum level, high CSF protein concentration, and
      involvement of deep regions of the brain (periventricular regions, basal ganglia,
      brainstem, and/or cerebellum) were significantly and independently associated
      with a worse survival. These five variables were used to design a prognostic
      score. Each variable was assigned a value of either 0, if favorable, or 1, if
      unfavorable. The values were then added together to arrive at a final score,
      which was tested in 105 assessable patients for which complete data of all five
      variables were available. The 2-year overall survival (OS) +/- SD was 80% +/- 8%,
      48% +/- 7%, and 15% +/- 7% (P =.00001) for patients with zero to one, two to
      three, and four to five unfavorable features, respectively. The prognostic role
      of this score was confirmed by limiting analysis to assessable patients treated
      with high-dose methotrexate-based chemotherapy (2-year OS +/- SD: 85% +/- 8%, 57%
      +/- 8%, and 24% +/- 11%; P =.0004). CONCLUSION: Age, PS, LDH serum level, CSF
      protein concentration, and involvement of deep structures of the brain were
      independent predictors of survival. A prognostic score including these five
      parameters seems advisable in distinguishing different risk groups in PCNSL
      patients. The proposed score and its relevance in therapeutic decision deserve to
      be validated in further studies.

PMID- 12525519
TI  - Additional prognostic value of bone marrow histology in patients subclassified
      according to the International Prognostic Scoring System for myelodysplastic
      syndromes.
AB  - PURPOSE: The most recent and powerful prognostic instrument established for
      myelodysplastic syndromes (MDS) is the International Prognostic Scoring System
      (IPSS), which is primarily based on medullary blast cell count, number of
      cytopenias, and cytogenetics. Although this prognostic system has substantial
      predictive power in MDS, further refinement is necessary, especially as far as
      lower-risk patients are concerned. Histologic parameters, which have long proved
      to be associated with outcome, are promising candidates to improve the prognostic
      accuracy of the IPSS. Therefore, we assessed the additional predictive power of
      the presence of abnormally localized immature precursors (ALIPs) and CD34
      immunoreactivity in bone marrow (BM) biopsies of MDS patients. PATIENTS AND
      METHODS: Cytogenetic, morphologic, and clinical data of 184 MDS patients, all
      from a single institution, were collected, with special emphasis on the
      determinants of the IPSS score. BM biopsies of 173 patients were analyzed for the
      presence of ALIP, and CD34 immunoreactivity was assessable in 119 patients. Forty
      nine patients received intensive therapy. RESULTS: The presence of ALIP and CD34
      immunoreactivity significantly improved the prognostic value of the IPSS, with
      respect to overall as well as leukemia-free survival, in particular within the
      lower-risk categories. In contrast to the IPSS, both histologic parameters also
      were predictive of outcome within the group of intensively treated MDS patients.
      CONCLUSION: Our data confirm the importance of histopathologic evaluation in MDS
      and indicate that determining the presence of ALIP and an increase in CD34
      immunostaining in addition to the IPSS score could lead to an improved prognostic
      subcategorization of MDS patients.

PMID- 12525520
TI  - Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients
      with recurrent or refractory ovarian or primary peritoneal carcinoma with
      overexpression of HER2: a phase II trial of the Gynecologic Oncology Group.
AB  - PURPOSE: To evaluate the feasibility, toxicity, and efficacy of single-agent
      monoclonal antibody therapy targeting the human epidermal growth factor receptor
      2 (HER2)/neu receptor in ovarian and primary peritoneal carcinoma. PATIENTS AND
      METHODS: Eligible patients had measurable persistent or recurrent epithelial
      ovarian or primary peritoneal carcinoma with 2+ or 3+ HER2 overexpression
      documented by immunohistochemistry. Intravenous trastuzumab was administered
      initially at a dose of 4 mg/kg, then weekly at 2 mg/kg. Patients without
      progressive disease or excessive toxicity could continue treatment indefinitely.
      Those with stable or responding disease at 8 weeks were offered treatment at a
      higher weekly dose (4 mg/kg) at time of progression. Patient sera were analyzed
      for the presence of the soluble extracellular domain of HER2, host antibodies
      against trastuzumab, and trastuzumab pharmacokinetics. RESULTS: A total of 837
      tumor samples were screened for HER2 expression, and 95 patients (11.4%)
      exhibited the requisite 2+/3+ expression level. Forty-five patients, all of whom
      received prior chemotherapy, were entered, and 41 were deemed eligible and
      assessable. There were only mild expected toxicities and no treatment-related
      deaths. Although an elevated level of the soluble extracellular domain of HER2
      was detected in eight of 24 patients, serum HER2 was not associated with clinical
      outcome. There was no evidence of host antitrastuzumab antibody formation. Serum
      concentrations of trastuzumab gradually increased with continued therapy. An
      overall response rate of 7.3% included one complete and two partial responses.
      Median treatment duration was 8 weeks (range, 2 to 104 weeks), and median
      progression-free interval was 2.0 months. CONCLUSION: The clinical value of
      single-agent trastuzumab in recurrent ovarian cancer is limited by the low
      frequency of HER2 overexpression and low rate of objective response among
      patients with HER2 overexpression.

PMID- 12525521
TI  - Phase II trial of irinotecan in patients with metastatic epithelial ovarian
      cancer or peritoneal cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of irinotecan in patients with
      metastatic platinum-resistant or platinum-refractory epithelial ovarian cancer or
      primary peritoneal cancer. PATIENTS AND METHODS: Thirty-one patients with
      measurable disease were enrolled in our study at The University of Texas M.D.
      Anderson Cancer Center. Twenty-five of these patients were treated with
      irinotecan at a dose of 300 mg/m2 intravenously for 90 minutes every 3 weeks; the
      remaining six patients were treated with 250 mg/m2 because their age was greater
      than 65 years. Median age was 57 years (range, 38 to 74 years). The majority
      (84%) had a Zubrod performance status of 0. All patients were evaluated for
      irinotecan toxicity, and 29 (94%) were evaluable for response. RESULTS: The
      overall response rate was 17.2%. One patient (3%) had a complete response, four
      (14%) had partial responses, 14 (48%) had stable disease, and 10 had (35%)
      disease progression. Median progression-free survival was 2.8 months (range, 1.1
      to 16 months), median duration of response was 1.4 months (range, 0.7 to 10.1
      months); median survival from primary diagnosis was 24.3 months (range, 6.5 to
      85.7 months); and median survival from initiation of irinotecan was 10.1 months
      (range, 2.3 to 34 months). Major toxicities included fatigue (16 patients),
      neutropenia (11 patients), diarrhea (nine patients), nausea (10 patients), and
      anorexia (seven patients). Eleven patients required dose reductions because of
      these toxicities. No treatment-related deaths occurred. CONCLUSION: Irinotecan
      has moderate efficacy and substantial toxicity in patients with metastatic
      platinum-resistant or platinum-refractory epithelial ovarian or primary
      peritoneal cancer.

PMID- 12525522
TI  - Randomized trial comparing six versus three cycles of epirubicin-based adjuvant
      chemotherapy in premenopausal, node-positive breast cancer patients: 10-year
      follow-up results of the French Adjuvant Study Group 01 trial.
AB  - PURPOSE: To evaluate the duration and dose intensity of epirubicin-based regimens
      in premenopausal patients with lymph node-positive breast cancer. PATIENTS AND
      METHODS: Between 1986 and 1990, 621 patients with operable breast cancer were
      randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500
      mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide
      (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six
      cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with
      epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All patients in the
      three arms received chest wall irradiation at the end of the third cycle.
      RESULTS: After a 131-month median follow-up, the 10-year disease-free survival
      (DFS) was 53.4%, 42.5%, and 43.6% (P =.05) in the three arms, respectively.
      Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P
      =.02) and to 3 FEC 75 (P =.05). The 10-year overall survival (OS) for the 6 FEC
      50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, it
      was 59.7% (P =.25), respectively. Pairwise comparisons demonstrate that 6 FEC 50
      was more effective than 3 FEC 50 (P =.10). Cox regression analysis demonstrates
      that OS was significantly better in the 6 FEC 50 than in the 3 FEC 50 arm (P
      =.046). No severe infections (grade 3 to 4), acute cardiac toxicity, or deaths
      from toxicity have been observed. Only five patients developed delayed cardiac
      dysfunctions, and three patients developed acute myeloblastic leukemia.
      CONCLUSION: After a long-term follow-up in an adjuvant setting, the benefit of
      six cycles of FEC 50 compared with three cycles, whatever the dose, is highly
      significant in terms of DFS. As regards OS, the group receiving six cycles of FEC
      50 has significantly better results than the group receiving three cycles of FEC
      50.

PMID- 12525523
TI  - Survivin, bcl-2, bax, and bcl-X gene expression in sentinel lymph nodes from
      melanoma patients.
AB  - PURPOSE: The expression of apoptosis-related genes, such as survivin, bcl-2, bcl
      X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction
      (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma
      patients and then correlated to the outcome of patients. PATIENTS AND METHODS:
      Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by
      Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and
      bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever
      possible, also by immunohistochemistry at the protein level. RESULTS: We found a
      significant correlation (P <.005) between survivin expression and outcome of
      patients; in fact, 61.5% of patients expressing survivin gene progressed or died
      because of the disease, whereas 38.5% are currently disease-free. Among patients
      negative for survivin expression, 100% are disease-free after a median follow-up
      time of 52.9 months. We did not find a significant correlation between bcl-2,
      bax, and bcl-X gene expression and outcome of patients. In fact, these genes were
      found equally expressed in patients with disease progression and in disease-free
      patients. CONCLUSION: Our findings show a variable expression of apoptosis
      related genes in SLNs of melanoma patients; more interestingly, we found that
      survivin expression correlates to outcome of patients in a statistically
      significant way, whereas the expression of other genes, such as bcl-2, bax, and
      bcl-X, did not seem to correlate to progression of disease. We suggest that the
      detection of survivin gene expression by RT-PCR in SLNs may be a useful
      prognostic indicator.

PMID- 12525524
TI  - Humoral immune response to a therapeutic polyvalent cancer vaccine after complete
      resection of thick primary melanoma and sentinel lymphadenectomy.
AB  - PURPOSE: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax
      Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen
      (TA90). However, endogenous immune responses to TA90 have also been reported.
      This study examined anti-TA90 antibody responses with respect to the survival of
      patients who received adjuvant vaccine immunotherapy after resection of thick (>
      or = 4 mm) primary cutaneous melanoma. PATIENTS AND METHODS: Serum specimens were
      obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after
      wide local excision of thick primary cutaneous melanoma and sentinel
      lymphadenectomy. All patients were offered adjuvant therapies with the vaccine,
      high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was
      used to determine serial serum titers of immunoglobulin G (IgG) and IgM
      antibodies against TA90. These titers were correlated with clinical course.
      RESULTS: Forty-three patients chose vaccine therapy, and 11 patients chose
      postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar
      for vaccine and observation groups (P =.184). At a median follow-up of 26 months,
      univariate analysis of Cox regression showed that disease-free survival and
      overall survival of vaccine patients were significantly correlated with maximal
      IgM response (P =.0006 and.006, respectively) but not with maximal IgG response
      (P =.73 and.95, respectively). Neither response predicted survival in the
      observation group. CONCLUSION: Postoperative vaccine therapy may enhance IgG and
      IgM immune responses to TA90 after surgical resection, but only the IgM response
      is correlated with improved survival. These findings may become useful to guide
      selection of patients for postoperative adjuvant therapy of high-risk melanoma.

PMID- 12525525
TI  - Weekly carboplatin and paclitaxel followed by concomitant paclitaxel,
      fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving
      therapy for advanced head and neck cancer.
AB  - PURPOSE: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel,
      infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX)
      administered every other week has resulted in 3-year survival rates of 60% of
      stage IV patients. Locoregional and distant failure rates were 13% and 23%,
      respectively. To reduce distant failure rates, we added a brief course of
      induction chemotherapy to TFHX. PATIENTS AND METHODS: Sixty-nine patients
      received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2)
      followed by five cycles of TFHX. RESULTS: Ninety-six percent had stage IV
      disease. Response to induction chemotherapy was partial response 52% and complete
      response (CR) 35%. Symptomatically, there was a significant reduction in mouth
      and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%).
      Best response following completion of TFHX was CR in 83%. Toxicities of TFHX
      consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At
      a median follow-up of 28 months, locoregional or systemic disease progression
      were each noted in five patients. The overall 3-year progression-free survival
      was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall
      survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%),
      respectively. At 12 months, five patients were completely feeding-tube dependent.
      CONCLUSION: Administration of carboplatin and paclitaxel before TFHX
      chemoradiotherapy results in high response activity and may decrease distant
      failure rates. Overall survival, progression, and organ preservation/functional
      outcome data support definitive evaluation of this approach.

PMID- 12525526
TI  - Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized
      controlled trial.
AB  - PURPOSE: Prognosis of patients with advanced oral cavity cancer is worth
      improving. Chemotherapy has been reported to be especially active in oral cavity
      tumors. Here we repeat the results of a randomized, multicenter trial enrolling
      patients with a resectable, stage T2-T4 (> 3 cm), N0-N2, M0 untreated, squamous
      cell carcinoma of the oral cavity. PATIENTS AND METHODS: Patients were randomly
      assigned to three cycles of cisplatin and fluorouracil followed by surgery
      (chemotherapy arm) or surgery alone (control arm). In both arms, postoperative
      radiotherapy was reserved to high-risk patients, and surgery was modulated
      depending on the tumor's closeness to the mandible. Patients' accrual was opened
      in 1989 and closed in 1999. It included 195 patients. RESULTS: In the
      chemotherapy arm, three toxic deaths were recorded. No significant difference in
      overall survival was found. Five-year overall survival was, for both arms, 55%.
      Postoperative radiotherapy was administered in 33% of patients in the
      chemotherapy arm, versus 46% in the control arm. A mandible resection was
      performed in 52% of patients in the control arm, versus 31% in the chemotherapy
      arm. CONCLUSION: The addition of primary chemotherapy to standard surgery was
      unable to improve survival. However, in this study, primary chemotherapy seemed
      to play a role in reducing the number of patients who needed to undergo
      mandibulectomy and/or radiation therapy. Variations in the criteria used to
      select patients for these treatment options may make it difficult to generalize
      these results, but there appears to be room for using preoperative chemotherapy
      to spare destructive surgery or radiation therapy in patients with advanced,
      resectable oral cavity cancer.

PMID- 12525527
TI  - Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study
      Group.
AB  - PURPOSE: To define patients and tumor characteristics as well as therapy results,
      patients with pelvic osteosarcoma who were registered in the Cooperative
      Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven
      patients with a high-grade pelvic osteosarcoma were eligible for this analysis.
      Fifteen patients had primary metastases. All patients received chemotherapy
      according to COSS protocols. Thirty-eight patients underwent limb-sparing
      surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo
      definitive surgery. Eleven patients received irradiation to the primary tumor
      site: four postoperatively and seven as the only form of local therapy. RESULTS:
      Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients
      (62%) who underwent definitive surgery. Five-year overall survival (OS) and
      progression-free survival rates were 27% and 19%, respectively. Large tumor size
      (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P
      <.0001) were poor prognostic factors. In 30 patients with no or intralesional
      surgery, 11 patients with radiotherapy had better OS than 19 patients without
      radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no
      or intralesional surgery, no radiotherapy, existence of primary metastasis
      (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no
      surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P
      =.0059) were independent poor prognostic factors. CONCLUSION: An operative
      approach with wide or marginal margins improves local control and OS. If the
      surgical margin is intralesional or excision is impossible, additional
      radiotherapy has a positive influence on prognosis.

PMID- 12525528
TI  - Metachronous skeletal osteosarcoma in patients treated with adjuvant and
      neoadjuvant chemotherapy for nonmetastatic osteosarcoma.
AB  - PURPOSE: The prognosis for patients who develop metachronous skeletal
      osteosarcoma (OS) has been considered grave compared with that for patients with
      relapse limited to the lungs. We investigated the incidence and outcome of
      metachronous skeletal OS after initial treatment of the primary tumor. PATIENTS
      AND METHODS: Twenty-three (median age 18.7 years) of 426 patients with
      nonmetastatic, high-grade primary OS treated at Memorial Sloan-Kettering Cancer
      Center (New York, NY) between February 1973 and May 2000 developed metachronous
      skeletal OS. Initial therapy included combination chemotherapy and surgery.
      Treatment of subsequent relapses consisted of chemotherapy or radiation alone or
      surgery with or without additional individualized chemotherapy. RESULTS: The
      median time from the diagnosis of primary OS to the development of metachronous
      OS was 1.4 years (range, 0.2 to 11.3 years). Median survival was 1.5 years (95%
      confidence interval [CI], 0.8 to 6.9 years). Two- and 5-year postmetachronous
      overall survival was 43.5% (95% CI, 23.2% to 63.7%) and 33% (95% CI, 13% to 53%),
      respectively. At last follow-up (range, 0.1 to 12.8 years), five (30.4%) patients
      were alive with no evidence of disease (range, 1.7 to 12.8 years; median, 4.4
      years). For 11 patients who developed metachronous OS 24 months or more from
      initial diagnosis, 5-year postmetachronous survival rate for patients receiving
      combined modality versus monotherapy was 83% (95% CI, 54% to 100%) and 40% (95%
      CI, 0% to 83%), respectively. CONCLUSION: In a small subset of patients who
      developed late metachronous OS, combined-modality therapy with surgery and
      aggressive chemotherapy may result in long-term postmetachronous survival. This
      implies that principles used in treatment of primary OS may be applied to
      patients with late metachronous skeletal OS.

PMID- 12525529
TI  - Combination of raltitrexed and oxaliplatin is an active regimen in malignant
      mesothelioma: results of a phase II study.
AB  - PURPOSE: The aim of this open-label phase II study was to evaluate the activity
      of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination
      therapy in patients with diffuse malignant pleural mesothelioma. PATIENT AND
      METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60
      years; World Health Organization performance status of < or = 2) were enrolled.
      Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2
      followed by oxaliplatin 130 mg/m2 every 3 weeks. RESULTS: Twenty-four patients
      (34%) were classified as having a poor prognosis. In the overall study
      population, 14 patients (20%) had a partial response, and 32 patients (46%) had
      stable disease. The symptomatic response rates were as follows: shortness of
      breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median
      time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22
      weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23
      to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks)
      from diagnosis of mesothelioma. In pretreated patients, median survival was 44
      weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI,
      63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was
      26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in
      chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated
      patients. Hematologic toxicity was mild, and there was no alopecia. The most
      common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no
      treatment-related deaths were reported. CONCLUSION: The raltitrexed and
      oxaliplatin combination is an active outpatient regimen in malignant mesothelioma
      and has an acceptable tolerability profile.

PMID- 12525530
TI  - Brief physician-initiated quit-smoking strategies for clinical oncology settings:
      a trial coordinated by the Eastern Cooperative Oncology Group.
AB  - PURPOSE: Although tobacco use by cancer patients increases the risk of relapse,
      diminishes treatment efficacy, and worsens quality of life, about one third of
      patients who smoked before their diagnosis continue to smoke. Because patients
      have regular contact with oncologists, the efficacy of a physician-based smoking
      cessation treatment was evaluated. METHODS: Cancer patients (n = 432) were
      randomly assigned to either usual care or a National Institutes of Health (NIH)
      physician-based smoking intervention. The primary outcome was 7-day point
      prevalence abstinence at 6 and 12 months after study entry. RESULTS: At the 6
      month follow-up, there was no significant difference in quit rates between the
      usual care (11.9%) and intervention (14.4%) groups, and there was no significant
      difference between the usual care (13.6%) and intervention (13.3%) groups at the
      12-month follow-up. Patients were more likely to have quit smoking at 6 months if
      they had head and neck or lung cancer, began smoking after the age of 16,
      reported at baseline using a cessation self-help guide or treatment in the last 6
      months, and showed greater baseline desire to quit. Patients were more likely to
      have quit smoking at 12 months if they smoked 15 or fewer cigarettes per day, had
      head and neck or lung cancer, tried a group cessation program, and showed greater
      baseline desire to quit. Finally, there was greater adherence among physicians to
      the NIH model for physician smoking treatment for patients in the intervention
      versus the usual care group. CONCLUSION: While training physicians to provide
      smoking cessation treatment to cancer patients can enhance physician adherence to
      clinical practice guidelines, physician smoking cessation interventions fail to
      yield significant gains in long-term quit rates among cancer patients.

PMID- 12525531
TI  - Epoetin alfa treatment results in clinically significant improvements in quality
      of life in anemic cancer patients when referenced to the general population.
AB  - PURPOSE: Anemia, highly common among cancer patients, is often an underlying
      cause of cancer-related fatigue and other quality-of-life (QOL) deficits.
      Although randomized clinical trials have shown that treatment with epoetin alfa
      increases hemoglobin levels, reduces fatigue, lessens transfusion requirements,
      and improves overall QOL, cancer-related anemia and fatigue remain undertreated.
      This is, in part, because scales and measures of QOL are still relatively
      unfamiliar to most clinicians and because population-based reference ranges are
      lacking, thus making clinical trial results difficult to interpret. METHODS: To
      aid in the interpretation of QOL results from clinical trials, we administered
      the Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL instrument to a
      nationally representative sample of 1,400 people using an Internet survey panel
      in the United States. We then compared the FACT-An data from the Internet survey
      with the QOL data of a 375-patient randomized, double-blind clinical trial
      evaluating epoetin alfa versus placebo in anemic cancer patients. RESULTS: FACT
      An, as administered to the survey population, displayed good psychometric
      properties and was able to discriminate between respondents with histories of
      specified illnesses, including anemia and cancer, and those without. Comparison
      of the population norm and clinical trial data showed that treatment with epoetin
      alfa resulted in clinically meaningful as well as statistically significant
      improvements in QOL (P <.01). CONCLUSION: Reliable population norm data are now
      available to aid in the interpretation of clinical trial results where the FACT
      An questionnaire is administered. In the clinical trial, treatment with epoetin
      alfa overcame much of the QOL deficit seen in anemic cancer patients compared
      with the norm population sample.

PMID- 12525532
TI  - Feasibility and compliance of automated measurement of quality of life in
      oncology practice.
AB  - PURPOSE: Systematic quality-of-life (QOL) assessment may have value in oncology
      practice by increasing awareness of a wide range of issues, possibly increasing
      detection of psychologic morbidity, social problems, and changes in physical
      status, and improving care and its outcomes. However, logistic problems are
      substantial. Automated systems solve many of these problems. We field-tested the
      feasibility and compliance that can be achieved using a computer touchscreen
      system in two consecutive studies. PATIENTS AND METHODS: In study 1, a
      prospective cohort of 272 patients was offered QOL assessment at each clinic
      appointment for 6 months. In study 2, all patients (N = 1,291) were offered QOL
      assessment as part of clinic routine during a 12-week period. RESULTS: In study
      1, 82% of patients agreed to take part, but over time, compliance was poor
      (median, 40%; mean, 43%) and deteriorated with longer follow-up. In study 2, the
      overall compliance was greatly increased (median, 100%; mean, 70%), and
      compliance was retained over multiple visits. In study 1, compliance was better
      in younger patients, males, and socially advantaged patients, but was not
      affected by the presence of depression or anxiety, or QOL. In the second study,
      building on experience in the first study, data collection and storage in the
      computer system was excellent, achieving 98% of collected data stored in one
      center. In general, patients were comfortable with the computers and the
      approach. Data collection on the wards was more difficult and less complete than
      in clinics, especially for patients undergoing acute admissions. CONCLUSION:
      Feasibility with higher compliance was demonstrated in study 2, in which the data
      collection was integrated into routine care, and can be improved with further
      technical initiatives and education of staff.

PMID- 12525533
TI  - Biology of prostate-specific antigen.
AB  - Prostate-specific antigen (PSA) is an androgen-regulated serine protease produced
      by both prostate epithelial cells and prostate cancer (PCa) and is the most
      commonly used serum marker for cancer. It is a member of the tissue kallikrein
      family, some of the members of which are also prostate specific. PSA is a major
      protein in semen, where its function is to cleave semenogelins in the seminal
      coagulum. PSA is secreted into prostatic ducts as an inactive 244-amino acid
      proenzyme (proPSA) that is activated by cleavage of seven N-terminal amino acids.
      PSA that enters the circulation intact is rapidly bound by protease inhibitors,
      primarily alpha1-antichymotrypsin, although a fraction is inactivated in the
      lumen by proteolysis and circulates as free PSA. This proteolytic inactivation,
      as well as the cleavage of proPSA to PSA, is less efficient in PCa. Serum total
      PSA levels are increased in PCa, and PSA screening has dramatically altered PCa
      presentation and management. Unfortunately, although high PSA levels are
      predictive of advanced PCa, a large fraction of organ-confined cancers present
      with much lower total PSA values that overlap those levels found in men without
      PCa. Measurement of free versus total PSA can increase specificity for PCa, and
      tests under development to measure forms of proPSA may further enhance the
      ability to detect early-stage PCa. PSA is also widely used to monitor responses
      to therapy and is under investigation as a therapeutic target. Finally, recent
      data indicate that there may be additional roles for PSA in the pathogenesis of
      PCa.

PMID- 12525534
TI  - Fanconi anaemia.
AB  - Fanconi anaemia (FA) is an autosomal recessive disease characterised by
      congenital abnormalities, defective haemopoiesis, and a high risk of developing
      acute myeloid leukaemia and certain solid tumours. Chromosomal instability,
      especially on exposure to alkylating agents, may be shown in affected subjects
      and is the basis for a diagnostic test. FA can be caused by mutations in at least
      seven different genes. Interaction pathways have been established, both between
      the FA proteins and other proteins involved in DNA damage repair, such as ATM,
      BRCA1 and BRCA2, thereby providing a link with other disorders in which defective
      DNA damage repair is a feature. This review summarises the clinical features of
      FA and the natural history of the disease, discusses diagnosis and management,
      and puts the recent molecular advances into the context of the cellular and
      clinical FA phenotype.

PMID- 12525535
TI  - A third MRX family (MRX68) is the result of mutation in the long chain fatty acid
      CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening
      mentally retarded patients.
AB  - BACKGROUND: The gene encoding fatty acid CoA ligase 4 (FACL4) is mutated in
      families with non-specific X linked mental retardation (MRX) and is responsible
      for cognitive impairment in the contiguous gene syndrome ATS-MR (Alport syndrome
      and mental retardation), mapped to Xq22.3. This finding makes this gene a good
      candidate for other mental retardation disorders mapping in this region. METHODS:
      We have screened the FACL4 gene in eight families, two MRX and six syndromic X
      linked mental retardation (MRXS), mapping in a large interval encompassing
      Xq22.3. RESULTS: We have found a missense mutation in MRX68. The mutation
      (c.1001C>T in the brain isoform) cosegregates with the disease and changes a
      highly conserved proline into a leucine (p.P375L) in the first luciferase domain,
      which markedly reduces the enzymatic activity. Furthermore, all heterozygous
      females showed completely skewed X inactivation in blood leucocytes, as happens
      in all reported females with other FACL4 point mutations or deletions.
      CONCLUSIONS: Since the FACL4 gene is highly expressed in brain, where it encodes
      a brain specific isoform, and is located in hippocampal and cerebellar neurones,
      a role for this gene in cognitive processes can be expected. Here we report the
      third MRX family with a FACL4 mutation and describe the development of a rapid
      enzymatic assay on peripheral blood that we propose as a sensitive, robust, and
      efficient diagnostic tool in mentally retarded males.

PMID- 12525536
TI  - The human Y chromosome's azoospermia factor b (AZFb) region: sequence, structure,
      and deletion analysis in infertile men.
AB  - Microdeletions of the Y chromosome long arm are the most common mutations in
      infertile males, where they involve one or more "azoospermia factors" (AZFa, b,
      and c). Understanding of the AZF structure and gene content and mapping of the
      deletion breakpoints in infertile men are still incomplete. We have assembled a
      complete 4.3 Mb map of AZFb and surrounding regions by means of 38 BAC clones.
      The proximal part of AZFb consists of large repeated sequences organised in
      palindromes, but most of it is single copy sequence. A number of known and novel
      genes and gene families map in this interval, and most of them are testis
      specific or have testis specific transcripts. STS mapping allowed us to identify
      four severely infertile subjects with a deletion in AZFb with similar
      breakpoints, therefore suggesting a common deletion mechanism. This deletion
      includes at least five single copy genes and two duplicated genes, but does not
      remove the historical AZFb candidate gene RBMY1. These data suggest that other
      genes in AZFb may have important roles in spermatogenesis. We had no evidence for
      homologous recombination between large repeats as a possible deletion mechanism,
      as shown for AZFa and AZFc. However, identical sequences in AZFb and AZFc exist,
      and this finding could explain deletions found in these regions.

PMID- 12525538
TI  - Differential targets of CpG island hypermethylation in primary and metastatic
      head and neck squamous cell carcinoma (HNSCC).
AB  - Head and neck squamous cell carcinomas (HNSCC) often metastasise to the cervical
      lymph nodes. It is known for HNSCC as well as other cancers that progression from
      normal tissue to primary tumour and finally to metastatic tumour is characterised
      by an accumulation of genetic mutations. DNA methylation, an epigenetic
      modification, can result in loss of gene function in cancer, similar to genetic
      mutations such as deletions and point mutations. We have investigated the DNA
      methylation phenotypes of both primary HNSCC and metastatic tumours from 13
      patients using restriction landmark genomic scanning (RLGS). With this technique,
      we were able to assess the methylation status of an average of nearly 1300 CpG
      islands for each tumour. We observed that the number of CpG islands
      hypermethylated in metastatic tumours is significantly greater than what is found
      in the primary tumours overall, but not in every patient. Interestingly, the data
      also clearly show that many loci methylated in a patient's primary tumour are no
      longer methylated in the metastatic tumour of the same patient. Thus, even though
      metastatic HNSCC methylate a greater proportion of CpG islands than do the
      primary tumours, they do so at different subsets of loci. These data show an
      unanticipated variability in the methylation state of loci in primary and
      metastatic HNSCCs within the same patient. We discuss two possible explanations
      for how different epigenetic events might arise between the primary tumour and
      the metastatic tumour of a person.

PMID- 12525539
TI  - In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani
      syndrome.
AB  - Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by
      short stature, brachydactyly, joint stiffness, and characteristic eye anomalies
      including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma.
      Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance
      have been described and a gene for AR WMS has recently been mapped to chromosome
      19p13.3-p13.2. Here, we report on the exclusion of chromosome 19p13.3-p13.2 in a
      large AD WMS family and show that, despite clinical homogeneity, AD and AR WMS
      are genetically heterogeneous entities. Because two AD WMS families were
      consistent with linkage to chromosome 15q21.1, the fibrillin-1 gene was sequenced
      and a 24 nt in frame deletion within a latent transforming growth factor-beta1
      binding protein (LTBP) motif of the fibrillin-1 gene was found in a AD WMS family
      (exon 41, 5074_5097del). This in frame deletion cosegregated with the disease and
      was not found in 186 controls. This study strongly suggests that AD WMS and
      Marfan syndrome are allelic conditions at the fibrillin-1 locus and adds to the
      remarkable clinical heterogeneity of type I fibrillinopathies.

PMID- 12525540
TI  - Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new
      nystagmus locus.
AB  - PURPOSE: To determine a gene locus for a family with a dominantly inherited
      vestibulocerebellar disorder characterised by early onset, but not congenital
      nystagmus. DESIGN: Observational and experimental study. METHODS: We carried out
      a phenotypic study of a unique four generation family with nystagmus. We
      performed genetic linkage studies including a genome wide search. RESULTS:
      Affected family members developed vestibulocerebellar type nystagmus in the first
      two years of life. A higher incidence of strabismus was noted in affected
      members. Haplotype construction and analysis of recombination events linked the
      disorder to a locus (NYS4) on chromosome 13q31-q33 with a lod score of 6.322 at
      theta=0 for D13S159 and narrowed the region to a 13.8 cM region between markers
      D13S1300 and D13S158. CONCLUSIONS: This study suggests that the early onset
      acquired nystagmus seen in this family is caused by a single gene defect.
      Identification of the gene may hold the key to understanding pathways for early
      eye stabilisation and strabismus.

PMID- 12525541
TI  - Identification of a mutation in the Indian Hedgehog (IHH) gene causing
      brachydactyly type A1 and evidence for a third locus.

PMID- 12525542
TI  - Non-syndromic recessive auditory neuropathy is the result of mutations in the
      otoferlin (OTOF) gene.

PMID- 12525543
TI  - Familial Sotos syndrome is caused by a novel 1 bp deletion of the NSD1 gene.

PMID- 12525544
TI  - P63 mutations are not a major cause of non-syndromic split hand/foot
      malformation.

PMID- 12525545
TI  - Beckwith-Wiedemann syndrome and assisted reproduction technology (ART).

PMID- 12525546
TI  - Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen
      homozygotes for DTDST mutation R279W.

PMID- 12525547
TI  - Chromosome 15 maternal uniparental disomy and psychosis in Prader-Willi syndrome.

PMID- 12525548
TI  - Beta 1-adrenergic antagonists and melatonin reset the clock and restore sleep in
      a circadian disorder, Smith-Magenis syndrome.

PMID- 12525549
TI  - Early onset asymmetrical intrauterine growth retardation with fetal hypokinesia
      and variable expression of acral and genitourinary malformations: a new lethal
      MCA syndrome.

PMID- 12525550
TI  - Hypogonadotrophic hypogonadism, short stature, cerebellar ataxia, rod-cone
      retinal dystrophy, and hypersegmented neutrophils: a novel disorder or a new
      variant of Boucher-Neuhauser syndrome?

PMID- 12525551
TI  - Quality of life in a family based genetic cascade screening programme for
      familial hypercholesterolaemia: a longitudinal study among participants.

PMID- 12525552
TI  - No association between the EN2 gene and autistic disorder.

PMID- 12525554
TI  - Deletion in the ABL gene resulting from a meiotic recombination of a maternal
      (3;22;9)(q22;q12;q34.1) translocation.

PMID- 12525553
TI  - No correlation between phenotype and genotype in boys with a truncating MECP2
      mutation.

PMID- 12525555
TI  - The severe form of type I hyperprolinaemia results from homozygous inactivation
      of the PRODH gene.

PMID- 12525557
TI  - CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European
      patients.

PMID- 12525556
TI  - Mutations in USH2A in Spanish patients with autosomal recessive retinitis
      pigmentosa: high prevalence and phenotypic variation.

PMID- 12525558
TI  - 2002 Dolph Adams Award.

PMID- 12525559
TI  - Rational approaches to human cancer immunotherapy.
AB  - Over most of the 20th century, immunotherapy for cancer was based on empiricism.
      Interesting phenomena were observed in the areas of cancer, infectious diseases,
      or transplantation. Inferences were made and extrapolated into new approaches for
      the treatment of cancer. If tumors regressed, the treatment approaches could be
      refined further. However, until the appropriate tools and reagents were
      available, investigators were unable to understand the biology underlying these
      observations. In the early 1990s, the first human tumor T cell antigens were
      defined and dendritic cells were discovered to play a pivotal role in antigen
      presentation. The current era of cancer immunotherapy is one of translational
      research based on known biology and rationally designed interventions and has led
      to a rapid expansion of the field. The beginning of the 21st century brings the
      possibility of a new era of effective cancer immunotherapy, combining rational,
      immunological treatments with conventional therapies to improve the outcome for
      patients with cancer.

PMID- 12525560
TI  - Actin cytoskeletal dynamics in T lymphocyte activation and migration.
AB  - Dynamic rearrangements of the actin cytoskeleton are crucial for the function of
      numerous cellular elements including T lymphocytes. They are required for
      migration of T lymphocytes through the body to scan for the presence of antigens,
      as well as for the formation and stabilization of the immunological synapse at
      the interface between antigen-presenting cells and T lymphocytes. Supramolecular
      activation clusters within the immunological synapse play an important role for
      the initiation of T cell responses and for the execution of T cell effector
      functions. In addition to the T cell receptor/CD3 induced actin nucleation via
      Wasp/Arp2/3-activation, signals through accessory receptors of the T cell (i.e.,
      costimulation) regulate actin cytoskeletal dynamics. In this regard, the actin
      binding proteins cofilin and L-plastin represent prominent candidates linking
      accessory receptor stimulation to the rearrangement of the actin cytoskeleton.
      Cofilin enhances actin polymerization via its actin-severing activity, and as a
      long-lasting effect, cofilin generates novel actin monomers through F-actin
      depolymerization. L-plastin stabilizes actin filament structures by means of its
      actin-bundling activity.

PMID- 12525561
TI  - A unique role for IL-23 in promoting cellular immunity.
AB  - Recent discoveries of interleukin (IL)-23, its receptor, and its signal
      transduction pathway add to our understanding of cellular immunity. IL-23 is a
      heterodimer, comprising IL-12 p40 and the recently cloned IL-23-specific p19
      subunit. IL-23 uses many of the same signal-transduction components as IL-12,
      including IL-12Rbeta1, Janus kinase 2, Tyk2, signal transducer and activator of
      transcription (Stat)1, Stat3, Stat4, and Stat5. This may explain the similar
      actions of IL-12 and IL-23 in promoting cellular immunity by inducing interferon
      gamma production and proliferative responses in target cells. Additionally, both
      cytokines promote the T helper cell type 1 costimulatory function of antigen
      presenting cells. IL-23 does differ from IL-12 in the T cell subsets that it
      targets. Whereas IL-12 acts on naive CD4+ T cells, IL-23 preferentially acts on
      memory CD4+ T cells. This review summarizes recent advances regarding IL-23,
      providing a functional and mechanistic basis for the unique niche that IL-23
      occupies in cellular immunity.

PMID- 12525562
TI  - Methimazole protects from experimental autoimmune uveitis (EAU) by inhibiting
      antigen presenting cell function and reducing antigen priming.
AB  - Methimazole (methyl-mercapto-imidazole, MMI), a compound used clinically in
      therapy of Graves' thyroiditis, was found to inhibit development of several
      autoimmune diseases in animal models. It was suggested on the basis of in vitro
      data that inhibition is through down-regulation of interferon-gamma (IFN-gamma)
      induced expression of major histocompatibility complex class I and class II
      molecules. Here, we investigate the effect of MMI on experimental autoimmune
      uveoretinitis (EAU) and study its mechanism(s). Treatment of EAU with MMI
      administered in drinking water inhibited induction of the disease and associated
      antigen (Ag)-specific proliferation and cytokine production by draining lymph
      node cells (LNCs). The treatment was protective only if administered during the
      first but not during the second week after immunization, suggesting an effect on
      the induction phase of EAU. It is interesting that MMI inhibited disease in IFN
      gamma knockout mice, indicating that the in vivo protective effect is IFN-gamma
      independent. Flow cytometric analysis of draining LNCs extracted 5 days after
      immunization showed that MMI partly to completely reversed the increase in Mac
      1(+)/class I(+)/class II(+) cells induced by immunization and reduced the
      proportion of B7-1 and CD40-positive cells, suggesting a deficit in the Ag
      presenting cell (APC) population. APC from untreated mice largely restored
      antigen-specific proliferation of MMI-treated LNCs. We suggest that MMI inhibits
      EAU at least in part by preventing the recruitment and/or maturation of APC,
      resulting in reduced generation of Ag-specific T cells.

PMID- 12525563
TI  - P-selectin mediates IL-13-induced eosinophil transmigration but not eotaxin
      generation in vivo: a comparative study with IL-4-elicited responses.
AB  - The study investigated the role of P-selectin in the responses of eosinophil
      transmigration and eotaxin generation in vivo elicited by interleukin (IL)-13, as
      compared with IL-4. Two murine models of leukocyte transmigration were used,
      migration into cytokine-stimulated peritoneal cavities and through stimulated
      cremasteric venules, as observed by intravital microscopy. In mice lacking P
      selectin, eosinophil infiltration elicited by the cytokines in the peritonitis
      model was totally inhibited. In the cremaster muscle, however, although
      spontaneous leukocyte-rolling flux and stimulated leukocyte firm adhesion were
      inhibited by approximately 97% and approximately 48%, respectively, stimulated
      transmigration was unaffected. However, IL-13-induced leukocyte transmigration
      was totally blocked in P-selectin-deficient mice treated with an anti-alpha(4)
      integrin monoclonal antibody (mAb; PS/2). In comparison, treatment of wild-type
      mice with the anti-alpha(4) integrin mAb resulted in only partial suppression of
      IL-13-induced leukocyte transmigration. Significant levels of eotaxin were
      detected in response to IL-13/IL-4 in both tissues in P-selectin-deficient
      animals. In conclusion, the regulatory role of P-selectin in leukocyte
      transmigration elicited by IL-13 appears to be tissue-specific, a phenomenon that
      is independent of the ability of the cytokine to stimulate eotaxin generation.

PMID- 12525564
TI  - Fructose-1,6-biphosphate and nucleoside pool modifications prevent neutrophil
      accumulation in the reperfused intestine.
AB  - Fructose-1,6-biphosphate (F16BP) attenuates ischemia/reperfusion (I/R) injury by
      inhibiting microvascular leukocyte adhesion or reducing neutrophil-derived oxygen
      free-radical production, but the causes of this action, the mechanisms in vivo,
      and the possible implication of nucleoside pool modifications are still
      controversial issues. We explored whether F16BP's inhibition of free-radical
      production and neutrophil recruitment is a result of its effect on adenosine
      (Ado) accumulation during intestinal I/R injury. The effects of F16BP
      administration were tested on the nucleotide/nucleoside metabolism at the end of
      the ischemic period and on microvascular neutrophil recruitment and free-radical
      production after reperfusion in vivo, in the presence or absence of Ado deaminase
      (ADA). Infusion of F16BP markedly increased endogenous Ado, decreased xanthine
      accumulation during the ischemic period, and inhibited neutrophil recruitment and
      subsequent neutrophil free-radical generation during reperfusion. Administration
      of ADA reversed these processes. The results provide strong evidence that F16BP
      prevents neutrophil accumulation and neutrophil free-radical generation during
      intestinal I/R by a key mechanism that modifies the nucleoside pool, leading to
      an endogenous accumulation of Ado and to a reduction of xanthine during ischemia.

PMID- 12525565
TI  - Malignant counterpart of myeloid dendritic cell (DC) belonging to acute
      myelogenous leukemia (AML) exhibits a dichotomous immunoregulatory potential.
AB  - Dendritic cells (DCs) play a central role in immune regulation. Some leukemic
      cells are argued to be malignant counterparts of DC because of their ability to
      differentiate into leukemic DC. We characterize DC-like leukemia homogenously
      expressing CD11c+CD86+ in acute myelogenous leukemia patients. They express the
      Wilms' tumor-1 antigen and common DC phenotypes (i.e., fascin+, CD83+, and DR+)
      directly. Purified leukemic cells produce interleukin-12 (IL-12) simultaneously
      with Fas ligand (FasL) and IL-6, which may suppress T cell-mediated immunity.
      These cells can elicit strong allogeneic T cell responses as well as induce tumor
      specific CD8+ cytotoxic T cells, suggesting that they effectively present tumor
      associated antigens. In contrast, they drive primary T cells toward apoptosis
      mediated in a tumor-specific way by a Fas-FasL interaction. Taken together, DC
      like leukemia uniquely influences immune surveillance in contradictory ways, some
      of which may be involved in the mechanism of immune escape.

PMID- 12525566
TI  - Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite
      sensitized allergic patients dysregulate the T cell response.
AB  - Although reports suggest that dendritic cells (DC) are involved in the allergic
      reaction characterized by a T helper cell type 2 (Th2) profile, the role of
      myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2,
      remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)
      sensitized allergic patients and in healthy donors, M-DC displayed a higher
      capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der
      p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin
      (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1
      pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80,
      and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic
      naive CD4(+) T cells from healthy donors, Der p 1-pulsed M-DC from allergic
      patients favored a Th1 profile [interferon (IFN)-gamma(high)/IL-4(low)] and Der p
      1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T
      cell polarization (IFN-gamma(low)/IL-4(low)) was induced by Der p 1-pulsed M-DC
      or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The
      neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led
      to an inhibition of IL-10 production by T cells and a polarization toward a type
      1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the
      balance between tolerance and allergic status. In addition, P-DC could contribute
      to the steady state in healthy donors or to the development of a Th2 response in
      allergic donors.

PMID- 12525567
TI  - Peripheral blood-derived bovine dendritic cells promote IgG1-restricted B cell
      responses in vitro.
AB  - Regulation of humoral responses involves multiple cell types including the
      requirements for cognate interactions between T and B cells to drive CD40
      dependent responses to T-dependent antigens. A third cell type has also been
      shown to play an essential role, the dendritic cell (DC). We demonstrate that
      bovine peripheral blood-derived (PB)-DC are similar in function to features
      described for human interstitial DC including the production of signature type 2
      cytokines [interleukin (IL)-13, IL-10]. PB-DC express moderate-to-high
      costimulatory molecule expression, and major histocompatibility complex class II
      is negative for CD14 expression and has low or no expression of CD11c. Consistent
      with the interstitial phenotype is the ability of PB-DC to influence B cell
      activation and differentiation via direct expression of CD40L and type 2
      cytokines. Collectively, these results suggest that direct B cell-DC interactions
      may promote an immunoglobulin-isotype expression pattern consistent with type 2
      responses, independent of direct T cell involvement.

PMID- 12525568
TI  - Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgE
      mediated histamine release in human basophils and downmodulate expression of the
      basophil-activation antigen CD203c/E-NPP3.
AB  - Recent data suggest that the statins, apart from their lipid-lowering activity,
      exhibit profound anti-inflammatory effects. Basophils are major proinflammatory
      effector cells in diverse pathologic reactions. We have examined the in vitro
      effects of five different statins on primary human basophils, their progenitors,
      and the basophil cell line KU-812. Preincubation of blood basophils with
      cerivastatin or atorvastatin (0.1-100 microM) for 24 h reduced their capacity to
      release histamine on immunoglobulin E (IgE)-dependent stimulation in a dose
      dependent manner. These statins also inhibited IgE-dependent up-regulation of the
      basophil-activation antigen CD203c. Moreover, both statins suppressed interleukin
      3-induced differentiation of basophils from their progenitors as well as (3)H
      thymidine uptake in KU-812 cells. All inhibitory effects of cerivastatin and
      atorvastatin were reversed by mevalonic acid (200 microM). The other statins
      tested (lovastatin, simvastatin, pravastatin) did not show significant inhibitory
      effects on basophils. Together, these data identify cerivastatin and atorvastatin
      as novel inhibitors of growth and activation of human basophils.

PMID- 12525569
TI  - Gap-junctional coupling between neutrophils and endothelial cells: a novel
      modulator of transendothelial migration.
AB  - Communication between leukocytes and endothelial cells is crucial for
      inflammatory reactions. Paracrine cross-talk and outside-in signaling (via
      adhesion molecules) have been characterized as communication pathways to date. As
      leukocytes and endothelial cells express connexins, we considered intercellular
      communication via gap junctions an intriguing additional concept. We found that
      gap-junctional coupling between neutrophils and endothelium occurred in a time
      dependent, bidirectional manner and was facilitated by adhesion. After blockade
      of connexins, transmigration of neutrophils through the endothelial layer was
      enhanced, and the barrier function of cell monolayers was reduced during
      transmigration. Tumor necrosis factor alpha decreased coupling. In the presence
      of connexins, transmigration of neutrophils did not alter permeability. Thus,
      neutrophils couple to endothelium via gap junctions, functionally modulating
      transmigration and leakiness. Gap-junctional coupling may be a novel way of
      leukocyte-endothelial communication.

PMID- 12525570
TI  - Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected
      mice and restrains their fratricide: role of Fas ligand down-regulation and MHC
      class II-transactivator up-regulation.
AB  - In the present work, we demonstrate that interleukin (IL)-4 is able to rescue B
      cells from Trypanosoma cruzi-infected mice, counteracting the strong apoptotic
      signals that these cells received in vivo. We have observed that IL-4 restrains
      the apoptosis of immunoglobulin (Ig)M(+) and IgG(+) B cells from infected and
      normal mice without inducing them to proliferate. In addition, IL-4 does not
      modify the quantity or quality of the antibodies secreted by B cells from
      infected mice, as it blocks their terminal differentiation to plasma cells and
      favors memory pathway. It is interesting that the protective effect of IL-4 over
      B cells from infected mice is mediated, at least partly, by the down-regulation
      of Fas ligand (FasL) expression, which leads to interference in the apoptosis
      executed by these B cells through the Fas/FasL death pathway. Accordingly, a
      marked up-regulation of the "FasL gene repressor" class II transactivator was
      observed, suggesting that this would be one mechanism underlying the IL-4
      mediated FasL down-regulation.

PMID- 12525571
TI  - Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic
      inflammation in a mouse model of retinal neovascularization.
AB  - Macrophages are important participants in neovascularization. This study was
      designed to examine the role of the monocyte/macrophage chemotactic proteins,
      monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein
      1alpha (MIP-1alpha) in a mouse model of oxygen-induced ischemic retinopathy and
      to determine whether the morphology and distribution of macrophages/microglia are
      concomitantly altered. The MCP-1, MIP-1alpha mRNA levels increased at 3 h after
      ischemia. MCP-1, MIP-1alpha, and vascular endothelial growth factor protein
      levels were also increased markedly and were maximal on days 1, 0.5, and 1,
      respectively, after ischemia. In situ hybridization showed that MCP-1 and MIP
      1alpha were localized in the hypoxic inner retina. Immunostaining demonstrated
      that the macrophages/microglia in the retina had morphological changes with
      enlarged processes, and some were closely associated with neovascular tufts at
      postnatal day 17. Coadministration of the neutralizing antibodies against MCP-1
      and MIP-1alpha inhibited retinal neovascularization by 30%. Our data suggest that
      MCP-1 and MIP-1alpha are involved in the induction of retinal neovascularization
      and play a role in the inflammation induced by the ischemic retinopathy, possibly
      by modulating or attracting macrophages/microglia.

PMID- 12525572
TI  - Adherence influences monocyte responsiveness to interleukin-10.
AB  - We studied the effects of adherence on the properties of interleukin (IL)-10 on
      monocyte-enriched peripheral blood mononuclear cells. We found that the decrease
      of CD11b expression induced by IL-10 was enhanced by adherence. Toll-like
      receptor (TLR)2 and TLR4 mRNA, as well as TLR4 surface expression, were
      significantly up-regulated by IL-10 in adherent cells. The absence of adherence
      prevented the inhibitory effects of IL-10 on lipopolysaccharide-induced tumor
      necrosis factor (TNF) and granulocyte-colony stimulating factor production and
      increased IL-1beta production and soluble TNF receptor II release in IL-10
      pretreated cells. Similarly, the absence of adherence amplified the enhancement
      of phagocytosis induced by IL-10. Tyk2 and signal transducer and activator of
      transcription 3 (STAT3) phosphorylation and suppressor of cytokine signaling 3
      (SOCS3) expression were induced by IL-10 in both conditions, but a longer
      activation and/or expression were observed in adherent monocytes. Finally, heme
      oxygenase-1, an anti-inflammatory molecule, was induced by IL-10 in adherent
      monocytes, whereas its expression remained low in nonadherent cells. Altogether,
      these data illustrate that adherence modulates the properties and the anti
      inflammatory effects of IL-10.

PMID- 12525573
TI  - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating
      polypeptide inhibit the production of inflammatory mediators by activated
      microglia.
AB  - Microglia play a central role in the regulation of immune and inflammatory
      activities, as well as tissue remodeling in the central nervous system. However,
      activation of microglia is a histopathological hallmark of several
      neurodegenerative diseases. Pathological microglial activation is believed to
      contribute to progressive damage in neurodegenerative diseases through the
      release of proinflammatory and/or cytotoxic factors, including tumor necrosis
      factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-12, and nitric oxide
      (NO). Hence, it is important to unravel mechanisms regulating microglia
      activation of inflamed brain parenchyma to provide insights into efficient
      therapeutic intervention. This study examines the role of two anti-inflammatory
      neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary
      adenylate cyclase-activating polypeptide (PACAP) on the production of various
      proinflammatory factors by endotoxin-stimulated microglia. VIP and PACAP inhibit
      TNF-alpha, IL-1beta, IL-6, and NO production by lipopolysaccharide (LPS)
      activated microglia. The specific type 1 VIP receptor mediates the inhibitory
      effect of VIP/PACAP, and cyclic adenosine monophosphate is the major, second
      messenger involved. VIP and PACAP regulate the production of these
      proinflammatory factors at a transcriptional level by inhibiting p65 nuclear
      translocation and nuclear factor-kappaB-DNA binding. This effect is mediated, as
      neuropeptides stabilize the inhibitor IkappaB by inhibiting LPS-induced IkappaB
      kinase activity. Therefore, the inhibitory effects on the production of
      proinflammatory mediators define VIP and PACAP as "microglia-deactivating
      factors" with significant, therapeutical potential for inflammatory/degenerative
      brain disorders.

PMID- 12525575
TI  - Tryptophan availability selectively limits NO-synthase induction in macrophages.
AB  - We studied the effects of tryptophan (TRP) availability on the synthesis and
      release of nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) in
      interferon-gamma (IFN-gamma)-activated murine macrophages of the BAC1.2F5 cell
      line. IFN-gamma (100 U/ml) not only increased the synthesis and release of NO and
      TNF-alpha from these cells but also induced indoleamine-2,3-dioxygenase, the rate
      limiting enzyme of TRP catabolism. This led to an increased metabolic flow
      through the kynurenine pathway and significantly decreased TRP levels in
      macrophage incubation media. Low TRP concentrations in the media, however,
      modified IFN-gamma effects. In TRP-"starved" cultures, in fact, the IFN-gamma
      mediated NO synthase induction was significantly reduced, and the increased TNF
      alpha synthesis and release were not affected. Our results suggest that a reduced
      local TRP availability may modify macrophage function and possibly the outcome of
      immune responses.

PMID- 12525574
TI  - Basophils express a type 2 cytokine profile on exposure to proteases from
      helminths and house dust mites.
AB  - The proteolytic activities frequently associated with sources of allergens and
      parasite secretions have been suggested as important immunomodulators. We have
      investigated whether the protease activity of the house dust mite allergen Der p1
      and the secreted proteases of the hookworm Necator americanus are able to
      directly induce type 2 cytokine production by basophils. Der p1 and the
      secretions of N. americanus induced interleukin (IL)-4, IL-5, and IL-13 but not
      interferon-gamma mRNA in KU812 basophils. Enzyme-linked immunosorbent assay
      confirmed that IL-4 and IL-13 were secreted. A nonproteolytic antigen failed to
      induce cytokine expression, and preincubation of Der p1 or N. americanus
      secretions with protease inhibitors inhibited cytokine expression. Data were
      confirmed using basophils purified from human peripheral blood. We speculate that
      this innate mechanism may contribute to the development of a cytokine milieu that
      could promote immunoglobulin E synthesis, eosinophil recruitment, and the
      development of type 2 T cells.

PMID- 12525576
TI  - Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a
      positive signaling receptor.
AB  - CD28 and cytotoxic T-lymphocyte antigen (CTLA)-4 are key coreceptors on the
      surface of T cells that have opposing effects on T cell activation. Although CD28
      enhances proliferation, CTLA-4 markedly inhibits the activation process. These
      opposing roles are particularly surprising given the structural similarity of the
      cytoplasmic residues of the two receptors. These include the related CD28(SDYMNM)
      and CTLA-4(GVYVKM) motifs. In this study, we have directly addressed whether
      these related motifs may play different roles in the activation process by
      swapping the CTLA-4(GVYVKM) motif with the CD28(SDYMNM) motif. Remarkably, stable
      transfectants of the T cell hybridoma DC27.10 showed that substitution of CTLA
      4(GVYVKM) was sufficient to convert CTLA-4 from a negative signaling coreceptor
      to a positive CD28-like coreceptor. CD28(SDYMNM) is therefore sufficient to
      convey positive signals within CTLA-4. These results demonstrate that
      CD28(SDYMNM) and CTLA-4(GVYVKM) motifs contain sufficient information to
      distinguish positive versus negative coreceptor signaling in T cells.

PMID- 12525577
TI  - OX52 is the rat homologue of CD6: evidence for an effector function in the
      regulation of CD5 phosphorylation.
AB  - The MRC OX52 monoclonal antibody is a marker of rat T lymphocytes. We have cloned
      by polymerase chain reaction the rat homologue of CD6, and fluorescein-activated
      cell sorter analysis and immunoprecipitations using OX52 in COS7 cells
      transfected with rat CD6 cDNA showed that CD6 is the cell-surface molecule
      recognized by OX52. Immunoprecipitation analysis showed that CD6 coprecipitated
      with CD5, which in turn, was coprecipitated equivalently with CD2, CD6, and the T
      cell receptor (TCR), but the fraction of CD5 associated with CD6 was highly
      phosphorylated in kinase assays, in marked contrast with the low level of
      phosphorylation of CD5 associated with TCR or CD2. Examination of protein kinases
      associating with these antigens showed that paradoxically, CD2 coprecipitated the
      highest amount of Lck and Fyn. CD6 also associated with Lck, Fyn, and ZAP-70,
      although at lower levels but additionally coprecipitated the Tec family kinase
      Itk, which is absent from CD2, CD5, and TCR complexes. Lck together with Itk was
      the best combination of kinases, effectively phosphorylating synthetic peptides
      corresponding to a cytoplasmic sequence of CD5. Overall, our results suggest that
      CD6 has an important role in the regulation of CD5 tyrosine phosphorylation,
      probably as a result of its unique feature of associating with kinases of
      different families.

PMID- 12525578
TI  - Cell type-dependent activation of 5-lipoxygenase by arachidonic acid.
AB  - 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory
      leukotrienes. We show that stimulation of polymorphonuclear leukocytes (PMNL),
      rat basophilic leukemia (RBL)-1, or transfected HeLa cells with arachidonic acid
      (AA) caused prominent 5-LO product formation that coincided with the activity of
      extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein
      kinase. 5-LO product formation in AA-stimulated PMNL and RBL-1 cells was
      independent of Ca2+. However, in HeLa cells expressing a 5-LO mutant lacking
      potential 5-LO phosphorylation sites, removal of Ca2+ caused a prominent loss of
      5-LO activity. For Mono Mac 6 (MM6) cells, AA failed to activate ERKs, and AA
      induced 5-LO product formation was only minute. Also, activation of ERKs by
      phorbol esters did not lead to prominent 5-LO product synthesis. Instead, 5-LO
      activation in MM6 cells required Ca2+ or alternative signaling pathways induced
      by hyperosmotic stress. In summary, mechanisms for activation of 5-LO differ
      considerably between cell types.

PMID- 12525579
TI  - The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis
      via an ERK-dependent pathway.
AB  - Several chemokines have been shown to regulate cellular apoptosis following
      discrete stimuli. It was previously demonstrated that the CC chemokine CCL1 (I
      309) rescues thymic lymphoma cells from apoptosis by unknown mechanisms. The aim
      of our study was to characterize the role of the CC chemokine receptor 8 (CCR8),
      the only described receptor for CCL1, in the rescue of murine thymic lymphoma
      cells and murine thymocytes from dexamethasone (dex)-induced apoptosis. We show
      here that the CCR8-restricted agonist Kaposi sarcoma-associated herpesvirus
      encoded chemokine viral macrophage-inflammatory protein-1 (vMIP-1) rescues thymic
      lymphoma cells from dex-induced apoptosis, similar to CCL1, and that such rescue
      is extracellular-regulated kinase-dependent. Although it has been hypothesized
      that the rescuing effect of CCL1 from apoptosis could be CCR8-mediated, here, we
      formally demonstrate the role of such receptor as its selective antagonist
      encoded by the MC148 gene of molluscum contagiosum virus MC148/vMCC-I inhibits v
      MIP-1- and CCL1-induced rescue activity. In addition, CCR8 ligands inhibit dex
      induced apoptosis of murine thymocytes with potential implications for thymic
      selection.

PMID- 12525580
TI  - Carotid artery stent placement--ready for prime time?

PMID- 12525581
TI  - Uterine artery embolization for fibroids: understanding the technical causes of
      failure.

PMID- 12525582
TI  - Limited uterine artery embolization with tris-acryl gelatin microspheres for
      uterine fibroids.
AB  - PURPOSE: To evaluate the midterm results of limited embolization of the uterine
      arteries in the management of symptomatic uterine fibroids and to evaluate the
      efficacy and safety of limited uterine artery embolization (UAE) with use of
      calibrated tris-acryl gelatin microspheres in the management of symptomatic
      uterine fibroids. MATERIALS AND METHODS: Twenty women (mean age, 43 years) with
      symptomatic uterine fibroids underwent bilateral embolization of the uterine
      arteries with use of calibrated microspheres. Devascularization of the fibroids
      was achieved and the main uterine artery was left patent in all women.
      Embolization was offered as an alternative to surgery in all women who had been
      treated unsuccessfully with medical therapy. RESULTS: All procedures were
      technically successful. Microspheres 700-900 micro m in diameter were used in 14
      women (70%). After a mean follow-up duration of 30.2 months (range, 24-48 mo),
      all women reported improvement in their symptoms, with 85% reporting complete
      resolution of menorrhagia at the most recent follow-up. One woman with multiple
      fibroids required a second embolization procedure because of persisting symptoms
      at 6 months. She is currently symptom-free after 48 months. In two women with
      submucosal fibroids, expulsion of necrotic fibroids occurred 2 and 7 months after
      the procedure, respectively. All women resumed normal menstruation after the
      procedure. One woman had a successful full-term pregnancy after embolization.
      CONCLUSION: Early experience with UAE with use of calibrated tris-acryl gelatin
      microspheres indicates that it is safe and efficacious in controlling
      menorrhagia.

PMID- 12525583
TI  - Intravascular ultrasound-guided direct intrahepatic portacaval shunt: description
      of technique and technical refinements.
AB  - PURPOSE: This is a prospective study designed to demonstrate the safety and
      feasibility of creating a direct inferior vena cava (IVC)-to-portal vein shunt
      with use of a new type of intravascular ultrasound (IVUS) to guide the puncture
      and completing the shunt with the use of a polytetrafluoroethylene (PTFE)-covered
      stent graft. MATERIALS AND METHODS: IVC-to-portal vein shunts were created in 31
      sequential patients for ascites (n = 31) or bleeding (n = 8). Transfemorally
      placed IVUS transducers were positioned in the IVC to guide the puncture from the
      IVC to the portal vein, which was performed from a transjugular approach with a
      modified Rosch-Uchida liver access set. A 9-MHz axial imaging IVUS system was
      used for the first 11 patients, and a variable 5-10-MHz sagittal IVUS imaging
      system was used for the next 20 patients. The shunts were completed with the use
      of single (n = 11) or overlapping (n = 20) PTFE-covered Palmaz stent-grafts,
      deployed primarily at a diameter of 8 mm. Patients were followed clinically and
      with US, venography, and inspection at liver transplantation to establish 30-day
      patency rates. RESULTS: All direct intrahepatic portacaval shunts (DIPSs) were
      created successfully. Both IVUS systems were able to adequately guide the portal
      vein puncture. Resolution and operator confidence were subjectively superior with
      the sagittal IVUS imaging system compared to the axial IVUS system. Two
      extrahepatic portal vein punctures occurred during the procedures. Both were
      controlled by the placement of sheaths and subsequent placement of stent-grafts.
      Both patients remained asymptomatic, although one required transfusion of blood
      products. The mean portosystemic gradient was reduced from 24 mm Hg before DIPS
      creation to 10 mm after DIPS creation. Embolization of varices was also performed
      in eight patients with history of recent gastrointestinal bleeding. Two patients
      died in the first week of acute liver failure. Two patients with hepatocellular
      carcinoma refused further follow-up. Of the 27 remaining patients, patency was
      demonstrated in all DIPS at 30 days by US, venography, or direct inspection at
      liver transplantation. CONCLUSIONS: IVUS-guided direct IVC-to-portal vein shunts
      may be created successfully with minimal complications. The use of a stent-graft
      is recommended for this procedure. Modifications of current technique and IVUS
      systems are described.

PMID- 12525584
TI  - Implications of problematic access in transluminal endografting of abdominal
      aortic aneurysm.
AB  - PURPOSE: Despite careful preoperative assessment, problematic access to the
      abdominal aorta for transluminal endografting (TE) of abdominal aortic aneurysm
      (AAA) is sometimes encountered. This study identifies preoperative risk factors
      predictive of problematic access and determines the impact of problematic access
      on outcomes. MATERIALS AND METHODS: Three hundred twenty-one consecutive TE
      procedures for AAA were divided into two groups: group A, which had access
      problems (n = 74), and group B, which had none (n = 247). RESULTS: Logistic
      regression analysis of risk factors showed that (i) a pulmonary risk score of 3
      (P <.001; odds ratio, 11.2), (ii) a hyperlipidemia score of 3 (P =.004; odds
      ratio, 2.6), and (iii) a small body (short height with low weight, P =.003; odds
      ratio, of 4.2) were independent risk factors for problematic access. Outcomes
      compared included rates of perioperative mortality, aborted procedure, surgical
      conversion, major complication, limb complication, and endoleak. The
      perioperative mortality rate was higher in group A (6.8% vs 1.2%; P =.018) and
      procedures were more likely to be aborted in patients in group A (12.2% vs 0%; P
      <.001). Rates of surgical conversion, major complication, and limb complication
      were not different between the two groups. The endoleak rate was higher in group
      B (10.8% vs 26.7%; P =.004). Logistic regression analysis showed that problematic
      access was an independent risk factor (P =.004; odds ratio, 12.0) for
      perioperative mortality. CONCLUSIONS: Moderate to severe chronic obstructive
      pulmonary disease and hyperlipidemia, both risk factors for atherosclerosis, were
      related to problematic access in this series. Small body size was another factor
      related to problematic access. Problematic access was an independent risk factor
      for perioperative mortality.

PMID- 12525585
TI  - Hemobahn stent-grafts for treatment of femoropopliteal arterial obstructions:
      midterm results of a prospective trial.
AB  - PURPOSE: To report a prospective study to evaluate safety, effectiveness, and
      midterm patency of self-expanding stent-grafts in patients with femoropopliteal
      occlusive disease. MATERIALS AND METHODS: Sixty-three Hemobahn stent-grafts were
      used in 52 patients for treatment of medium- or long-segment (>3 cm) occlusions
      (82.7%) and stenoses (17.3%) of the femoropopliteal artery. The mean length of
      vessel segments covered was 10.9 cm +/- 5.13. Follow-up with documentation of
      clinical symptoms, assessment of Rutherford clinical stage of peripheral vascular
      disease, and color-coded duplex sonography was performed at discharge, at 1, 3,
      6, 12, 18, and 24 months after implantation, and yearly thereafter. Mean follow
      up duration was 23.8 months +/- 6.9 (range, 8-36 mo). Follow-up data at 12 and 24
      months after treatment were available for 47 of 52 (90.4%) and 31 of 52 patients
      (59.6%), respectively. RESULTS: Device implantation was technically successful in
      all 52 patients, yielding an overall technical success rate of 100%. Procedure
      related complications were observed in 12 of 52 patients (23.1%) and consisted of
      distal embolization (n = 4, 7.7%), minor groin hematoma (n = 7, 13.5%), and
      arteriovenous fistula (n = 1, 1.9%), but prolonged hospitalization and further
      medical, interventional, or surgical measures were not required. Stent-graft
      placement induced an initial improvement of the mean resting ankle-brachial index
      from 0.54 +/- 0.12 to 0.89 +/- 0.14 (P <.01). Primary patency rates at 12 and 24
      months were 78.4% +/- 5.8 and 74.1% +/- 6.2, respectively. Primary assisted
      patency rates were 82.4% +/- 5.3 at 12 months and 80.3% +/- 5.6 at 24 months.
      Secondary patency rates at 12 and 24 months were 88.3% +/- 4.5 and 83.2% +/- 5.5,
      respectively. There was no significant difference (log-rank test, P >.3) between
      primary patency rates in patients grouped according to lengths of implanted
      grafts (ie, length of the treated lesions). CONCLUSION: Endovascular placement of
      Hemobahn stent-grafts for percutaneous treatment of medium- to long-segment high
      grade stenoses and occlusions of the femoropopliteal artery is a safe procedure
      with excellent initial success rates and promising midterm results.

PMID- 12525586
TI  - Pretreatment imaging workup for patients with intermittent claudication: a cost
      effectiveness analysis.
AB  - PURPOSE: To determine the optimal imaging strategy in pretreatment workup of
      patients with intermittent claudication with use of noninvasive imaging
      modalities and intraarterial digital subtraction angiography (DSA). MATERIALS AND
      METHODS: A decision-analytic model that considered test characteristics such as
      sensitivity, complications induced by the test, implications of missing lesions,
      and the consequences of overtreating patients, was developed to evaluate the
      societal cost-effectiveness (CE) of magnetic resonance (MR) angiography, duplex
      ultrasonography (US), and DSA. Our main outcome measures were quality-adjusted
      life years (QALYs), lifetime costs (in dollars), and incremental CE ratios. The
      base-case analysis considered a cohort of 60-year old male patients without a
      history of coronary artery disease who presented with severe claudication to
      undergo pretreatment imaging workup. RESULTS: The range in effectiveness and
      lifetime costs among different diagnostic workup strategies was small (largest
      difference in effectiveness: 0.025 QALYs; largest difference in lifetime costs:
      $1,800). If treatment was limited to angioplasty in patients with suitable
      lesions, MR angiography had an incremental CE ratio of $35,000 per QALY compared
      with no diagnostic workup, and DSA had an incremental CE ratio of $471,000 per
      QALY compared with MR angiography. If treatment options included both angioplasty
      and bypass surgery, DSA had an incremental CE ratio of $179,000 per QALY compared
      with no diagnostic workup, and MR angiography and duplex US were less effective
      and more costly. CONCLUSIONS: The differences in costs and effectiveness among
      diagnostic imaging strategies for patients with intermittent claudication are
      slight and MR angiography or duplex US can replace DSA without substantial loss
      in effectiveness and with a slight cost reduction.

PMID- 12525587
TI  - Radiologic placement of side-hole catheter with tip fixation for hepatic arterial
      infusion chemotherapy.
AB  - PURPOSE: To investigate the technical outcome of radiologic catheter placement
      with use of a side-hole catheter with distal fixation for hepatic arterial
      infusion chemotherapy. MATERIALS AND METHODS: Between January 1993 and September
      1999, 426 patients were referred to our department to undergo intraarterial
      infusion chemotherapy for unresectable malignant liver tumors. A subclavian
      artery was exposed under local anesthesia and a catheter was inserted. After
      inserting the tip of the side-hole catheter into the gastroduodenal artery,
      splenic artery, or peripheral branch of the hepatic artery, the catheter tip was
      fixed to the vessel with use of coils and a mixture of n-butyl cyanoacrylate
      (NBCA) and iodized oil. The proximal end of the catheter was connected to an
      implanted port, and the port system was embedded subcutaneously. RESULTS:
      Placement was successful in 425 of 426 patients (99.8%) in a mean time of 76
      minutes. Catheter dislodgement was noted in 12 patients (2.8%). Cumulative
      patency rates of the hepatic artery calculated according to the Kaplan-Meier
      method for the entire group were 91.0%, 81.4%, and 58.1% at 6 months and 1 and 2
      years, respectively. Complications related to catheter placement were observed in
      nine cases and included dysfunction of the implanted system (n = 3), significant
      bleeding around the implanted port (n = 2), improper infusion of NBCA and iodized
      oil (n = 2), and cerebral infarction (n = 2). CONCLUSION: Radiologic catheter
      placement via a subclavian artery with side-hole catheter placement with distal
      fixation for hepatic arterial infusion chemotherapy is a highly successful
      procedure with a reduced risk of catheter dislodgment and arterial occlusion.

PMID- 12525588
TI  - Pregnancy outcomes after fallopian tube recanalization: oil-based versus water
      soluble contrast agents.
AB  - PURPOSE: To determine the pregnancy outcomes in patients undergoing fallopian
      tube recanalization (FTR) with use of oil-based versus water-soluble contrast
      agents. MATERIALS AND METHODS: Ninety-three patients with unilateral or bilateral
      proximal tubal occlusion confirmed by hysterosalpingography or laparoscopy
      underwent FTR with use of water-soluble contrast material alone (n = 50) or also
      had an oil-based agent injected into each tube after recanalization (n = 43).
      Pregnancy rates and outcomes of the two groups were studied retrospectively.
      RESULTS: With respect to differences between groups, only the body mass index
      proved to be a significant predictor (oil, 28.4; water, 24.7; P =.008). Mean age,
      duration of infertility, type of infertility, and initial diagnosis were
      comparable. There was a weak trend toward a higher pregnancy rate in the oil
      based contrast material group, but it was not significant (P =.64). The average
      time to pregnancy was 4.4 months with use of oil-based contrast material,
      compared to 7.7 months with use of only water-soluble contrast material (P =.03).
      CONCLUSION: The use of an oil-based agent had little effect on the rate of
      conception, but time to conception was reduced by more than 3 months.

PMID- 12525589
TI  - Clinical services in interventional radiology: results from the national Medicare
      database and a Society of Interventional Radiology membership survey.
AB  - PURPOSE: To evaluate trends in evaluation and management (E & M) services
      performed by interventional radiologists. MATERIALS AND METHODS: Recent national
      Medicare physician utilization data (1997-2000) were analyzed for trends in E & M
      services provided by interventional radiologists. The results were evaluated in
      conjunction with a recent Society of Interventional Radiology (SIR) membership
      survey in which 165 interventional radiology (IR) practices answered questions
      about clinical service issues. RESULTS: Despite the perception of frequent
      clinical services by interventional radiologists, paid Medicare claims for E & M
      services have increased only minimally, from 9,472 to 9,662 (+2.0%), and have
      lagged behind non-E & M procedural services, which have increased from 2,283,111
      to 2,527,323 (+10.7%). The relative value unit (RVU) impact of E & M encounters
      has increased from 14,422 to 14,893 (+3.2%) while the RVU impact of procedural
      services has increased from 2,262,991 to 3,723,486 (+64.5%). E & M services
      account for only 0.39% of all Medicare claims, 0.49% of service RVUs, and 0.68%
      of all reimbursable time spent by interventionalists. However, when surveyed,
      interventional radiologists perceived that E & M services are much more frequent:
      92% provide clinical services and indicate that 6.6% +/- 5.4 of physician time is
      spent providing E & M services. CONCLUSION: Despite perceptions by interventional
      radiologists that E & M services are common, Medicare claims for such services
      are infrequent and growth lags behind that of IR services overall. These
      discrepancies may be explained in part by practice and billing infrastructures
      that do not effectively translate actual clinical services into successful
      claims.

PMID- 12525591
TI  - In vitro stability of tris-acryl gelatin microspheres in a multipharmaceutical
      chemoembolization solution.
AB  - PURPOSE: To evaluate the in vitro stability of tris-acryl gelatin microspheres
      (TAGMs) in a multipharmaceutical solution as a preliminary step before planned
      hepatic chemoembolization with TAGMs. MATERIALS AND METHODS: Half-cm(3) aliquots
      of 100-300- micro m and 300-500- micro m TAGMs were suspended in 1 mL of normal
      saline solution (NSS), 1 mL of ethiodized oil, or 1 mL of a standard
      chemoembolization solution (cisplatin 100 mg, doxorubicin 50 mg, mitomycin 10 mg,
      ethiodized oil 3 mL, and iodixanol 5 mL). Mixtures were incubated at 37 degrees C
      for 24 hours and were then examined visually and with use of light microscopy.
      Solutions containing ethiodized oil required centrifugation for separation.
      Determination of average sphere diameter after 24-hour chemoembolization
      incubation was performed after washing in ethanol, washing in acetone, and
      rinsing in 0.9% aqueous sodium chloride solution. RESULTS: TAGMs in NSS had no
      gross degradation, were intact on light microscopy, and had no visually
      perceptible change in average diameter. TAGMs in ethiodized oil alone appeared to
      dissolve into a cloudy solution; however, centrifugation separated spheres from
      ethiodized oil as a layer, which was intact on light microscopy. Spheres
      incubated in the chemoembolization solution were not grossly visible as a result
      of the deep red color of doxorubicin (which stained the spheres), but were easily
      seen after centrifugation. There were similar numbers of spheres per field on
      microscopy with a minimal (but significant) increase in analyzed diameter.
      CONCLUSION: TAGMs are stable in a standard chemoembolization solution and may be
      suitable as a substitute for PVA particles in hepatic chemoembolization.

PMID- 12525592
TI  - Pathologic evaluation of a spherical polyvinyl alcohol embolic agent in a porcine
      renal model.
AB  - PURPOSE: To evaluate the effects of a spherical embolic agent consisting of
      polyvinyl alcohol (PVA) and to compare this agent with commercially available
      embolization agents. MATERIALS AND METHODS: Eleven miniature pigs were included
      in the study population. The upper poles of both kidneys were selected as the
      target organs for embolization. PVA spheres (700-900 micro m) were used in nine
      kidneys, PVA particles (500-710 micro m) were used in six kidneys, gelatin
      spheres (700-900 micro m) were used in five kidneys, and gold-colored gelatin
      spheres (700-900 micro m) were used in three kidneys. Two animals were killed
      immediately after embolization. In the remaining animals, angiography was
      performed before sacrifice 7 days (in five pigs) or 28 days (in four pigs) after
      embolization. Pathologic and histologic evaluation of the kidneys was performed.
      RESULTS: All agents resulted in target vessel occlusion and end-organ infarction.
      All arteries embolized with spherical agents were recanalized at follow-up
      angiography. In vessels embolized with PVA particles, the occluding plug
      consisted of thrombus and PVA. In vessels embolized with spherical agents, the
      occluding plug consisted mostly of the embolic agent. PVA spheres were associated
      with the mildest inflammatory responses at 7 and 28 days when compared with PVA
      particles and gelatin-based microspheres. Arterial wall destruction was seen to a
      greater extent in kidneys embolized with gelatin-based microspheres than in those
      embolized with PVA-based agents. CONCLUSIONS: The spherical, PVA-based
      embolization agent resulted in target organ infarction and temporary arterial
      occlusion. The inflammatory response to PVA spheres was significantly less
      aggressive than the response to other agents tested. Further study with clinical
      and long-term pathologic follow-up is suggested to determine if these findings
      may have favorable clinical implications for patients undergoing embolization
      procedures.

PMID- 12525593
TI  - Alteplase: stability and bioactivity after dilution in normal saline solution.
AB  - PURPOSE: To characterize the biochemical stability and bioactivity of
      reconstituted alteplase when diluted to a concentration of 0.01 mg/mL in normal
      saline solution and stored at ambient temperature for as long as 24 hours in
      commercial saline solution bags. MATERIALS AND METHODS: Two commercially
      available formulations of lyophilized alteplase (2-mg and 50-mg vials,
      respectively) were reconstituted with sterile water to a final concentration of 1
      mg/mL. For each vial configuration, 5 mg of alteplase (5 mL) was added to a
      commercial 500-mL bag of normal saline solution to achieve a 0.01-mg/mL targeted
      concentration. Solutions were assayed for optical clarity, pH, protein
      concentration, and in-vitro clot lysis activity. Assays of the solutions were
      performed at time points of 0 (control), 4, 8, and 24 hours at ambient room
      temperature and compared to controls. RESULTS: On visual inspection, aliquots of
      the diluted protein solutions in clear glass vials remained clear/colorless after
      24 hours. Bioactivity (clot lysis assay) over the course of 24 hours at ambient
      temperature remained essentially unchanged relative to control (2-mg vial: mean
      of 98.3%, range of 93.7%-103.3%; 50-mg vial: mean of 103.1%, range of 100.6%
      108.3%). The mean protein recovery rates (relative to targeted concentration)
      over a 24-hour period were 43% (range, 39%-46%) and 42% (range, 40%-45%) for the
      2-mg and 50-mg vial configurations, respectively. CONCLUSIONS: Alteplase diluted
      in normal saline solution at a concentration of 0.01 mg/mL is biochemically
      stable and active at ambient temperature for as long as 24 hours as assessed by
      in vitro clot lysis assays. Alteplase appears to have a bimodal solubility
      profile in normal saline solution and further studies are required to determine
      the activity and solubility of alteplase concentrations lower than 0.01 mg/mL.

PMID- 12525594
TI  - Improvement of sonographic needle visibility in cirrhotic livers during
      transjugular intrahepatic portosystemic stent-shunt procedures with use of real
      time compound imaging.
AB  - The visibility of a transjugular intrahepatic portosystemic stent-shunt (TIPS)
      puncture needle was assessed with use of real-time compound imaging and single
      line ultrasonography (US). In vitro and in vivo, needle-tissue contrast was
      calculated. With an increasing angle of incidence, the decrease in needle
      visibility was more pronounced for single-line US than for compound imaging. At
      angles of incidence of more than 30 degrees, the needle was barely visible with
      either technique. Subjective evaluation during TIPS procedures in 10 patients
      proved that the needle tip was significantly better seen with compound imaging.
      Therefore, real-time compound imaging significantly improved contrast and
      subjective visibility of the needle.

PMID- 12525595
TI  - Percutaneous embolization of the pancreatic duct with cyanoacrylate tissue
      adhesive in disconnected duct syndrome.
AB  - Traditionally, patients with chronic end-pancreatic fistulas caused by pancreatic
      necrosis have been treated with long-term percutaneous catheter drainage and/or
      surgical procedures such as resection or open drainage. With surgical treatment,
      the endocrine and exocrine functions of the removed pancreatic segment are
      sacrificed. Surgery in this patient population presents additional risks because
      of the inflammatory changes of pancreatitis and associated venous thromboses. The
      authors devised a method of percutaneous embolization of the pancreatic duct in a
      patient with catheter-dependent pancreatic fistula who wished to avoid surgery.
      The procedure was performed under fluoroscopic guidance with use of a
      microcatheter and wire system to access the duct, which was embolized with
      opacified n-butyl cyanoacrylate tissue adhesive. After 1 year of surveillance,
      the patient remains symptom-free. There has been no need for replacement of the
      drainage catheter and no further intervention has been performed.

PMID- 12525597
TI  - Conventional versus modified technique for percutaneous nephrostomy in newborns
      and young infants.
AB  - Percutaneous nephrostomy (PN) in newborns and young infants presents unique
      challenges. Twenty-six consecutive PN procedures in 18 patients were
      retrospectively reviewed. Fifteen procedures were performed with the conventional
      micropuncture technique. The modified technique describe herein was used in 11
      procedures. Depending on whether there is obstruction and whether the obstruction
      is at the ureteropelvic junction level or distal to it, the technique selected
      will vary.

PMID- 12525598
TI  - Axillary artery traumatic pseudoaneurysm managed with a Wallgraft Endoprothesis.

PMID- 12525599
TI  - Latency in human immunodeficiency virus type 1 infection: no easy answers.

PMID- 12525600
TI  - Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein
      fusion intermediate at two sites.
AB  - Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires
      folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N
      HR and C-HR hairpins, which brings viral and target cell membranes together to
      facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41
      are potent inhibitors of HIV infection. Here we report new findings on the
      mechanism of inhibition of a N-HR peptide and compare these data with inhibition
      by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic
      conditions, we show that the N-HR peptide preferentially binds receptor-activated
      Env and that CD4 binding is sufficient for triggering conformational changes that
      allow the peptide to bind Env, results similar to those seen with the C-HR
      peptide. However, activation by both CD4 and chemokine receptors further enhances
      Env binding by both peptides. We also show that a nonconservative mutation in the
      N-HR of gp41 abolishes C-HR peptide but not N-HR peptide binding to gp41. These
      results indicate that there are two distinct sites in receptor-activated Env that
      are potential targets for drug or vaccine development.

PMID- 12525601
TI  - Mouse polyomavirus utilizes recycling endosomes for a traffic pathway independent
      of COPI vesicle transport.
AB  - Mouse polyomavirus enters host cells internalized, similar to simian virus 40
      (SV40), in smooth monopinocytic vesicles, the movement of which is associated
      with transient actin disorganization. The major capsid protein (VP1) of the
      incoming polyomavirus accumulates on membranes around the cell nucleus. Here we
      show that unlike SV40, mouse polyomavirus infection is not substantially
      inhibited by brefeldin A, and colocalization of VP1 with beta-COP during early
      stages of polyomavirus infection in mouse fibroblasts was observed only rarely.
      Thus, these viruses obviously use different traffic routes from the plasma
      membrane toward the cell nucleus. At approximately 3 h postinfection, a part of
      VP1 colocalized with the endoplasmic reticulum marker BiP, and a subpopulation of
      virus was found in perinuclear areas associated with Rab11 GTPase and colocalized
      with transferrin, a marker of recycling endosomes. Earlier postinfection, a minor
      subpopulation of virions was found to be associated with Rab5, known to be
      connected with early endosomes, but the cell entry of virus was slower than that
      of transferrin or cholera toxin B-fragment. Neither Rab7, a marker of late
      endosomes, nor LAMP-2 lysosomal glycoprotein was found to colocalize with
      polyomavirus. In situ hybridization with polyomavirus genome-specific fluorescent
      probes clearly demonstrated that, regardless of the multiplicity of infection,
      only a few virions delivered their genomic DNA into the cell nucleus, while the
      majority of viral genomes (and VP1) moved back from the proximity of the nucleus
      to the cytosol, apparently for their degradation.

PMID- 12525602
TI  - Membrane association facilitates the correct processing of pp220 during
      production of the major matrix proteins of African swine fever virus.
AB  - The African swine fever (ASF) virus polyprotein pp220 is processed at Gly-Gly-X
      sites by a virally encoded SUMO-like protease to produce matrix proteins p150,
      p37, p34, and p14. Four Gly-Gly-X sites are used to produce the matrix proteins,
      but the polyprotein contains an additional 15 sites potentially recognized by the
      protease. This study shows that cleavage occurs at many, if not all, Gly-Gly-X
      sites, and at steady state, p150 and p34 are minor products of processing.
      Significantly, only the final structural proteins, p150 and p34, were found in
      mature virions, suggesting that there is a mechanism for excluding incorrectly
      processed forms. ASF virus is assembled on the cytoplasmic face of the
      endoplasmic reticulum, and the distribution of pp220 products between membranes
      and cytosol was studied. Incorrectly processed forms of p34 were recovered from
      both the cytosol and membrane fractions. Interestingly, p34 was only detected in
      the membrane fraction, and of the many processed forms bound to membranes, only
      p34 was protected from trypsin, suggesting envelopment. The majority of the
      incorrectly processed forms of p150 were recovered from the cytosol. Again, the
      correct product of processing, p150, was selectively recruited to membranes.
      Sucrose density centrifugation showed that membrane-associated forms of p34 and
      p150 assembled into large structures suggestive of a viral matrix, while
      cytosolic and/or incorrectly processed forms of pp220 did not. Taken together,
      these results suggest that association with cellular membranes is important for
      regulating the correct processing of pp220 and the packaging of matrix proteins
      into virions.

PMID- 12525603
TI  - Properly folded nonstructural polyprotein directs the semliki forest virus
      replication complex to the endosomal compartment.
AB  - The late RNA synthesis in alphavirus-infected cells, generating plus-strand RNAs,
      takes place on cytoplasmic vacuoles (CPVs), which are modified endosomes and
      lysosomes. The cytosolic surface of CPVs consists of regular membrane
      invaginations or spherules, which are the sites of RNA synthesis (P. Kujala, A.
      Ikaheimonen, N. Ehsani, H. Vihinen, P. Auvinen, and L. Kaariainen J. Virol.
      75:3873-3884, 2001). To understand how CPVs arise, we have expressed the
      individual Semliki Forest virus (SFV) nonstructural proteins nsP1 to nsP4 in
      different combinations, as well as their precursor polyprotein P1234 and its
      cleavage intermediates. A complex of nsPs was obtained from P123 or P1234,
      indicating that the precursor stage is essential for the assembly of the
      polymerase complex. To prevent the processing of the polyprotein and its cleavage
      intermediates, constructs with the mutation C478A (designated with a superscript
      CA) in the active site of the protease domain of nsP2 were used. Uncleaved
      polyproteins containing nsP1 were membrane bound and palmitoylated, and those
      containing nsP3 were phosphorylated, reflecting properties of authentic nsP1 and
      nsP3, respectively. Similarly, polyproteins containing nsP1 or nsP2 had enzymatic
      activities specific for the individual proteins, indicating that they were
      correctly folded in the precursor state. Uncleaved P12(CA) was localized almost
      exclusively to the plasma membrane and filopodia, like nsP1 alone, whereas
      P12(CA)3 and P12(CA)34 were found on cytoplasmic vesicles, some of which
      contained late endosomal markers. In immunoelectron microscopy these vesicles
      resembled CPVs in SFV-infected cells. Our results indicate that the nsP1 domain
      alone is responsible for the membrane association of the nonstructural
      polyprotein, whereas the nsP1 domain together with the nsP3 domain targets it to
      the intracellular vesicles.

PMID- 12525604
TI  - Vigorous innate and virus-specific cytotoxic T-lymphocyte responses to murine
      cytomegalovirus in the submaxillary salivary gland.
AB  - To better understand the immunological mechanisms that permit prolonged shedding
      of murine cytomegalovirus (MCMV) from the salivary gland, the phenotypic and
      functional characteristics of leukocytes infiltrating the submaxillary gland
      (SMG) were analyzed in infected BALB/c mice. A robust innate immune response,
      comprised of CD11c+ major histocompatibility complex class II+ CD11b- CD8alpha+
      dendritic cells and gamma/delta T-cell receptor-bearing CD3+ T cells was
      prominent through at least 28 days postinfection. Concurrently, a dramatic
      increase in pan-NK (DX5+) CD3+ and CD8+ T cells was observed, while CD4+ T cells,
      known to be essential for viral clearance from this tissue, increased slightly.
      The expression particularly of gamma interferon but also of interleukin-10 and CC
      chemokines was extraordinarily high in the SMG in response to MCMV infection. The
      gamma interferon was produced primarily by CD4+ and CD8+ T lymphocytes and DX5+
      CD3+ T cells. The SMG CD8+ T cells were highly cytolytic ex vivo, and a
      significant proportion of these cells were specific to an immunodominant MCMV
      peptide. These peptide-specific clones were not exhausted by the presence of high
      virus titers, which persisted in the SMG despite the strength of the cell
      mediated responses. In contrast, MCMV replication was efficiently cleared from
      the draining cervical and periglandular lymph nodes, a tissue displaying a
      substantially weaker antiviral response. Our data indicated that vigorous innate
      and acquired immune responses are elicited, activated, and retained in response
      to mucosal inflammation from persistent MCMV infection of the submaxillary gland.

PMID- 12525605
TI  - The natural host range shift and subsequent evolution of canine parvovirus
      resulted from virus-specific binding to the canine transferrin receptor.
AB  - Canine parvovirus (CPV) is a host range variant of a feline virus that acquired
      the ability to infect dogs through changes in its capsid protein. Canine and
      feline viruses both use the feline transferrin receptor (TfR) to infect feline
      cells, and here we show that CPV infects canine cells through its ability to
      specifically bind the canine TfR. Receptor binding on host cells at 37 degrees C
      only partially correlated with the host ranges of the viruses, and an
      intermediate virus strain (CPV type 2) bound to higher levels on cells than did
      either the feline panleukopenia virus or a later strain of CPV. During the
      process of adaptation to dogs the later variant strain of CPV gained the ability
      to more efficiently use the canine TfR for infection and also showed reduced
      binding to feline and canine cells compared to CPV type 2. Differences on the top
      and the side of the threefold spike of the capsid surface controlled specific TfR
      binding and the efficiency of binding to feline and canine cells, and these
      differences also determined the cell infection properties of the viruses.

PMID- 12525606
TI  - Arenavirus-mediated liver pathology: acute lymphocytic choriomeningitis virus
      infection of rhesus macaques is characterized by high-level interleukin-6
      expression and hepatocyte proliferation.
AB  - Lymphocytic choriomeningitis virus (LCMV) and Lassa virus can cause hemorrhagic
      fever and liver disease in primates. The WE strain of LCMV (LCMV-WE) causes a
      fatal Lassa fever-like disease in rhesus macaques and provides a model for
      arenavirus pathogenesis in humans. LCMV-WE delivered intravenously or
      intragastrically to rhesus macaques targets hepatocytes and induces high levels
      of liver enzymes, interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), and
      soluble tumor necrosis factor receptors (sTNFRI and -II) in plasma during acute
      infection. Proinflammatory cytokines TNF-alpha and IL-1beta were not detected in
      plasma of infected animals, but increased plasma gamma interferon was noted in
      fatally infected animals. Immunohistochemistry of acute liver biopsies revealed
      that 25 to 40% of nuclei were positive for proliferation antigen Ki-67. The
      increases in IL-6, sIL-6R, sTNFR, and proliferation antigen that we observe are
      similar to the profile of incipient liver regeneration after surgical or toxic
      injury (N. Fausto, Am. J. Physiol. 277:G917-G921, 1999). Although IL-6 was not
      directly induced by virus infection in vitro, peripheral blood mononuclear cells
      from acutely infected monkeys produced higher levels of IL-6 upon
      lipopolysaccharide stimulation than did healthy controls. Our data confirm that
      acute infection is associated with weak inflammatory responses in tissues and
      initiates a program of liver regeneration in primates.

PMID- 12525607
TI  - A G protein-coupled receptor encoded by rhesus rhadinovirus is similar to ORF74
      of Kaposi's sarcoma-associated herpesvirus.
AB  - Rhesus rhadinovirus (RRV) is a gamma-2 herpesvirus and is the rhesus macaque
      homologue of human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma
      associated herpesvirus. DNA sequence analysis of RRV indicates that it shares
      numerous open reading frames (ORFs) with HHV-8, including one (ORF74) encoding a
      seven-transmembrane-spanning G protein-coupled receptor (GPCR) with similarity to
      cellular chemokine receptors. Examination of the predicted amino acid sequence of
      RRV ORF74 reveals that it encodes a seven-transmembrane-spanning GPCR sharing
      40.8% amino acid sequence identity with HHV-8 ORF74 and 24.1% amino acid sequence
      identity with rhesus macaque CXCR2. In addition, immunofluorescence studies
      indicate that an epitope-tagged version of RRV ORF74 is expressed on the surfaces
      of transfected cells, suggesting that this protein is in fact a membrane
      receptor. In in vitro cell culture assays, RRV ORF74 possesses transforming
      potential, as NIH 3T3 clones stably expressing the receptor demonstrate an
      increased ability to grow in soft agarose and to induce tumor formation in nude
      mice. Further analysis of RRV ORF74 indicates that expression of the receptor in
      NIH 3T3 cells causes an increased secretion of vascular endothelial growth factor
      and activation of the ERK1/2 (p44/42) mitogen-activated protein kinase signaling
      pathway. The results of these studies suggest that RRV ORF74 encodes a GPCR with
      properties similar to those of its homologue in HHV-8 and that this gene may play
      a role in RRV-associated pathogenesis.

PMID- 12525608
TI  - Role of plasma membrane lipid microdomains in respiratory syncytial virus
      filament formation.
AB  - The fusion protein (F) of respiratory syncytial virus (RSV) is the envelope
      glycoprotein responsible for the characteristic cytopathology of syncytium
      formation. RSV has been shown to bud from selective areas of the plasma membrane
      as pleomorphic virions, including both filamentous and round particles. With
      immunofluorescent microscopy, we demonstrated evidence of RSV filaments
      incorporating the fusion protein F and colocalizing with a lipid microdomain
      specific fluorescent dye, 1,1-dihexadecyl-3,3,3,3-tetramethylindocarbocyanine
      perchlorate. Western blot analysis of Triton X-100 cold-extracted membrane
      fractions confirmed the presence of RSV proteins within the lipid microdomains.
      RSV proteins also colocalized with cellular proteins associated with lipid
      microdomains, caveolin-1, and CD44, as well as with RhoA, a small GTPase. ADP
      ribosylation of RhoA by Clostridium botulinum exotoxin inactivated RhoA signaling
      and resulted in the absence of RSV-induced syncytia despite no significant change
      in viral titer. We demonstrated an overall decrease in both the number and length
      of the viral filaments and a shift in the localization of F to nonlipid
      microdomain regions of the membrane in the presence of C3 toxin. This suggests
      that the selective incorporation of RSV proteins into lipid microdomains during
      virus assembly may lead to critical interactions of F with cellular proteins,
      resulting in microvillus projections necessary for the formation of filamentous
      virus particles and syncytium formation. Thus, manipulation of membrane lipid
      microdomains may lead to alterations in the production of viral filaments and RSV
      pathogenesis and provide a new pharmacologic target for RSV therapy.

PMID- 12525609
TI  - Rotavirus nonstructural protein NSP5 interacts with major core protein VP2.
AB  - Rotavirus is a nonenveloped virus with a three-layered capsid. The inner layer,
      made of VP2, encloses the genomic RNA and two minor proteins, VP1 and VP3, with
      which it forms the viral core. Core assembly is coupled with RNA viral
      replication and takes place in definite cellular structures termed viroplasms.
      Replication and encapsidation mechanisms are still not fully understood, and
      little information is available about the intermolecular interactions that may
      exist among the viroplasmic proteins. NSP2 and NSP5 are two nonstructural
      viroplasmic proteins that have been shown to interact with each other. They have
      also been found to be associated with precore replication intermediates that are
      precursors of the viral core. In this study, we show that NSP5 interacts with VP2
      in infected cells. This interaction was demonstrated with recombinant proteins
      expressed from baculovirus recombinants or in bacterial systems. NSP5-VP2
      interaction also affects the stability of VP6 bound to VP2 assemblies. The data
      presented showed evidence, for the first time, of an interaction between VP2 and
      a nonstructural rotavirus protein. Published data and the interaction
      demonstrated here suggest a possible role for NSP5 as an adapter between NSP2 and
      the replication complex VP2-VP1-VP3 in core assembly and RNA encapsidation,
      modulating the role of NSP2 as a molecular motor involved in the packaging of
      viral mRNA.

PMID- 12525610
TI  - Phosphorylation of rubella virus capsid regulates its RNA binding activity and
      virus replication.
AB  - Rubella virus is an enveloped positive-strand RNA virus of the family
      TOGAVIRIDAE: Virions are composed of three structural proteins: a capsid and two
      membrane-spanning glycoproteins, E2 and E1. During virus assembly, the capsid
      interacts with genomic RNA to form nucleocapsids. In the present study, we have
      investigated the role of capsid phosphorylation in virus replication. We have
      identified a single serine residue within the RNA binding region that is required
      for normal phosphorylation of this protein. The importance of capsid
      phosphorylation in virus replication was demonstrated by the fact that
      recombinant viruses encoding hypophosphorylated capsids replicated at much lower
      titers and were less cytopathic than wild-type virus. Nonphosphorylated mutant
      capsid proteins exhibited higher affinities for viral RNA than wild-type
      phosphorylated capsids. Capsid protein isolated from wild-type strain virions
      bound viral RNA more efficiently than cell-associated capsid. However, the RNA
      binding activity of cell-associated capsids increased dramatically after
      treatment with phosphatase, suggesting that the capsid is dephosphorylated during
      virus assembly. In vitro assays indicate that the capsid may be a substrate for
      protein phosphatase 1A. As capsid is heavily phosphorylated under conditions
      where virus assembly does not occur, we propose that phosphorylation serves to
      negatively regulate binding of viral genomic RNA. This may delay the initiation
      of nucleocapsid assembly until sufficient amounts of virus glycoproteins
      accumulate at the budding site and/or prevent nonspecific binding to cellular RNA
      when levels of genomic RNA are low. It follows that at a late stage in
      replication, the capsid may undergo dephosphorylation before nucleocapsid
      assembly occurs.

PMID- 12525611
TI  - A structurally disordered region at the C terminus of capsid plays essential
      roles in multimerization and membrane binding of the gag protein of human
      immunodeficiency virus type 1.
AB  - Crystal structures of human immunodeficiency virus type 1 (HIV-1) capsid protein
      (CA) reveal that the last 11 C-terminal amino acids are disordered. This
      disordered region contains a glycine-rich sequence 353-GVGGP-357 (numbering
      refers to the initiation methionine of Gag) that is highly conserved within the
      Gag proteins of HIV-1, HIV-2, and simian immunodeficiency virus, which suggests
      the importance of this sequence in virus replication. In the present study, we
      demonstrate that changing any individual residue within this short region in the
      context of the full-length HIV-1 genome virtually abolishes production of
      extracellular virus particles, in either the presence or absence of viral
      protease activity. This severe defect in virus particle production results from
      impaired Gag multimerization, as well as from decreased Gag association with the
      cellular membranes, as demonstrated by the results of gradient sedimentation and
      membrane flotation centrifugation assays. These findings are further supported by
      the diffuse distribution pattern of the mutant Gag within the cytoplasm, as
      opposed to the punctate distribution of the wild-type Gag on the plasma membrane.
      On the basis of these results, we propose that the disordered feature of amino
      acid stretch 353-GVGGP-357 in the CA crystal forms may have allowed Gag to adopt
      multiple conformations and that such structural flexibility is needed by Gag in
      order to construct geometrically complex particles.

PMID- 12525612
TI  - The core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin encoded by bovine
      herpesvirus 4 was acquired from an ancestor of the African buffalo.
AB  - The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only viral gene known to
      date that encodes a homologue of the cellular core 2 beta-1,6-N
      acetylglucosaminyltransferase-mucin type (C2GnT-M). To investigate the origin and
      evolution of the Bo17 gene, we analyzed its distribution among BoHV-4 strains and
      determined the sequences of Bo17 from nine representative strains and of the
      C2GnT-M gene from six species of ruminants expected to encompass the group within
      which the gene acquisition occurred. Of 34 strains of BoHV-4, isolated from four
      different continents, all were found to contain the Bo17 gene. Phylogenetic
      analyses indicated that Bo17 was acquired from a recent ancestor of the African
      buffalo, implying that cattle subsequently acquired BoHV-4 by cross-species
      transmission. The rate of synonymous nucleotide substitution in Bo17 was
      estimated at 5 x 10(-8) to 6 x 10(-8) substitutions/site/year, consistent with
      previous estimates made under the assumption that herpesviruses have cospeciated
      with their hosts. The Bo17 gene acquisition was dated to around 1.5 million years
      ago. Bo17 sequences from BoHV-4 strains from African buffalo and from cattle
      formed two separate clades, estimated to have split about 700,000 years ago.
      Analysis of the ratio of nonsynonymous to synonymous nucleotide substitutions
      revealed a burst of amino acid replacements subsequent to the transfer of the
      cellular gene to the viral genome, followed by a return to a strong constraint on
      nonsynonymous changes during the divergence of contemporary BoHV-4 strains. The
      Bo17 gene represents the most recent of the known herpesvirus gene acquisitions
      and provides the best opportunity for learning more about this important process
      of viral evolution.

PMID- 12525613
TI  - Biochemical and functional characterization of the Ebola virus VP24 protein:
      implications for a role in virus assembly and budding.
AB  - The VP24 protein of Ebola virus is believed to be a secondary matrix protein and
      minor component of virions. In contrast, the VP40 protein of Ebola virus is the
      primary matrix protein and the most abundant virion component. The structure and
      function of VP40 have been well characterized; however, virtually nothing is
      known regarding the structure and function of VP24. Wild-type and mutant forms of
      VP24 were expressed in mammalian cells to gain a better understanding of the
      biochemical and functional nature of this viral protein. Results from these
      experiments demonstrated that (i) VP24 localizes to the plasma membrane and
      perinuclear region in both transfected and Ebola virus-infected cells, (ii) VP24
      associates strongly with lipid membranes, (iii) VP24 does not contain N-linked
      sugars when expressed alone in mammalian cells, (iv) VP24 can oligomerize when
      expressed alone in mammalian cells, (v) progressive deletions at the N terminus
      of VP24 resulted in a decrease in oligomer formation and a concomitant increase
      in the formation of high-molecular-weight aggregates, and (vi) VP24 was present
      in trypsin-resistant virus like particles released into the media covering VP24
      transfected cells. These data indicate that VP24 possesses structural features
      commonly associated with viral matrix proteins and that VP24 may have a role in
      virus assembly and budding.

PMID- 12525614
TI  - Alphavirus minus-strand synthesis and persistence in mouse embryo fibroblasts
      derived from mice lacking RNase L and protein kinase R.
AB  - We report our studies to probe the possible role of the host response to double
      stranded RNA in cessation of alphavirus minus-strand synthesis. Mouse embryo
      fibroblasts (MEF) from Mx1-deficient mice that also lack either the protein
      kinase R (PKR) or the latent RNase L or both PKR and RNase L were screened. In
      RNase L-deficient but not wild-type or PKR-deficient MEF, there was continuous
      synthesis of minus-strand templates and the formation of new replication
      complexes producing viral plus strands. Inhibiting translation caused minus
      strand synthesis to stop and a loss of transcription activity of the mature
      replication complexes. This turnover of replication complexes that were stable in
      cells containing RNase L suggested that RNase L plays some role, albeit possibly
      indirect, in the formation of stable replication complexes during alphavirus
      infection. In addition, confluent monolayers of RNase L-deficient murine cells
      readily established persistent infections and were not killed. This phenotype is
      contrary to what has been observed for infection in vertebrate cells with a
      presumably functional RNase L gene and more resembled alphavirus replication in
      Aedes mosquito cells, in which the activity of replication complexes making plus
      stands was also found to decay with inhibition of translation.

PMID- 12525615
TI  - Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function
      independently as late budding domains: involvement of host proteins TSG101 and
      VPS-4.
AB  - The VP40 protein of Ebola virus can bud from mammalian cells in the form of lipid
      bound, virus-like particles (VLPs), and late budding domains (L-domains) are
      conserved motifs (PTAP, PPxY, or YxxL; where "x" is any amino acid) that
      facilitate the budding of VP40-containing VLPs. VP40 is unique in that potential
      overlapping L-domains with the sequences PTAP and PPEY are present at amino acids
      7 to 13 of VP40 (PTAPPEY). L-domains are thought to function by interacting with
      specific cellular proteins, such as the ubiquitin ligase Nedd4, and a component
      of the vacuolar protein sorting (vps) pathway, tsg101. Mutational analysis of the
      PTAPPEY sequence of VP40 was performed to understand further the contribution of
      each individual motif in promoting VP40 budding. In addition, the contribution of
      tsg101 and a second member of the vps pathway, vps4, in facilitating budding was
      addressed. Our results indicate that (i) both the PTAP and PPEY motifs contribute
      to efficient budding of VP40-containing VLPs; (ii) PTAP and PPEY can function as
      L-domains when separated and moved from the N terminus (amino acid position 7) to
      the C terminus (amino acid position 316) of full-length VP40; (iii) A VP40
      PTAP/tsg101 interaction recruits tsg101 into budding VLPs; (iv) a VP40
      PTAP/tsg101 interaction recruits VP40 into lipid raft microdomains; and (v) a
      dominant-negative mutant of vps4 (E228Q), but not wild-type vps4, significantly
      inhibited the budding of Ebola virus (Zaire). These results provide important
      insights into the complex interplay between viral and host proteins during the
      late stages of Ebola virus budding.

PMID- 12525616
TI  - Phosphorylated serine residues and an arginine-rich domain of the moloney murine
      leukemia virus p12 protein are required for early events of viral infection.
AB  - Mutational analyses of the p12 Gag phosphoprotein of Moloney murine leukemia
      virus have demonstrated its participation in both virus assembly and the early
      stages of infection. The molecular mechanisms by which p12 functions in these
      events are still poorly understood. We performed studies to examine the
      significance of p12 phosphorylation in the viral life cycle. Alanine
      substitutions were introduced at the potential phosphorylation sites in p12, and
      the resulting mutants were tested for replication. Mutant viruses with changes at
      S61 and S78 were severely impaired, whereas the other mutant viruses were viable.
      S61 was shown to be required for normal levels of phosphorylation of p12 in vivo.
      These defective mutant viruses showed no apparent alteration to Gag protein
      processing or reduction in the yield of virions after transient transfection, but
      the mutants failed to form circular viral DNAs in acutely infected cells.
      Sequence analysis of revertant clones derived from S(61,65)A mutant virus
      revealed two classes: one group with a single mutation at a residue adjacent to
      S61 and another group with mutations introducing new positive charges surrounding
      S61. In vivo [32P]orthophosphate labeling indicated that the rescue of the
      S(61,65)A mutant virus did not result in a significant increase in the
      phosphorylation level of p12. Alanine substitutions of an arginine-rich stretch
      near S61 (at R-66, -68, -70, and -71) resulted in the same phenotype as the
      S(61,65)A mutant virus. The restored function of S(61,65)A mutant virus by second
      or third site mutations may result from a structural change or the addition of
      positively charged residues in the arginine-rich region.

PMID- 12525617
TI  - Enhancer-like activity of a brome mosaic virus RNA promoter.
AB  - As with transcription from DNA templates, RNA synthesis from viral RNA templates
      must initiate accurately. RNA sequences named specificity and initiation
      determinants allow recognition of and coordinated interaction with the viral
      replication enzyme. Using enriched replicase from brome mosaic virus (BMV)
      infected plants and variants of the promoter template for minus-strand and
      subgenomic RNA initiation, we found that a specificity determinant for minus
      strand initiation could function at variable distances and positions from the 3'
      initiation site in a manner similar to enhancers of transcription from DNA
      templates. This determinant's addition could convert a cellular tRNA into a
      template for RNA synthesis by the BMV replicase in vitro. Furthermore, the same
      specificity element could direct internal initiation, which occurred at a highly
      preferred site in a manner distinct from initiation at the 3' terminus of the
      template. These results document two distinct modes of initiation site
      recognition by a viral RNA replicase.

PMID- 12525618
TI  - Compartmentalization and transmission of multiple epstein-barr virus strains in
      asymptomatic carriers.
AB  - Infection with the Epstein-Barr virus (EBV) is often subclinical in the presence
      of a healthy immune response; thus, asymptomatic infection is largely
      uncharacterized. This study analyzed the nature of EBV infection in 20
      asymptomatic immunocompetent hosts over time through the identification of EBV
      strain variants in the peripheral blood and oral cavity. A heteroduplex tracking
      assay specific for the EBV gene LMP1 precisely identified the presence of
      multiple EBV strains in each subject. The strains present in the peripheral blood
      and oral cavity were often completely discordant, indicating the existence of
      distinct infections, and the strains present and their relative abundance changed
      considerably between time points. The possible transmission of strains between
      the oral cavity and peripheral blood compartments could be tracked within
      subjects, suggesting that reactivation in the oral cavity and subsequent
      reinfection of B lymphocytes that reenter the periphery contribute to the
      maintenance of persistence. In addition, distinct virus strains persisted in the
      oral cavity over many time points, suggesting an important role for epithelial
      cells in the maintenance of persistence. Asymptomatic individuals without
      tonsillar tissue, which is believed to be an important source of virus for the
      oral cavity, also exhibited multiple strains and a cyclic pattern of transmission
      between compartments. This study revealed that the majority of patients with
      infectious mononucleosis were infected with multiple strains of EBV that were
      also compartmentalized, suggesting that primary infection involves the
      transmission of multiple strains. Both the primary and carrier states of
      infection with EBV are more complex than previously thought.

PMID- 12525619
TI  - Peripheral blood cytotoxic gammadelta T lymphocytes from patients with human
      immunodeficiency virus type 1 infection and AIDS lyse uninfected CD4+ T cells,
      and their cytocidal potential correlates with viral load.
AB  - Progression of human immunodeficiency virus type 1 (HIV-1) infection in humans is
      marked by declining CD4+-T-cell counts and increasing virus load (VL). Cytotoxic
      T lymphocytes (CTL) play an important role in the lysis of HIV-infected cells,
      especially during the early phase of asymptomatic infection. CTL responses in the
      later phase of disease progression may not be as effective since progressors with
      lower CD4+-T-cell counts have consistently higher VL despite having elevated CTL
      counts. We hypothesized that, apart from antiviral effects, some CTL might also
      contribute to AIDS pathogenesis by depleting CD4+ T cells and that this CTL
      activity may correlate with the VL in AIDS patients. Therefore, a cross-sectional
      study of 31 HIV-1-infected patients at various clinical stages was carried out.
      Purified CTL from these donors as well as HIV-seronegative controls were used as
      effectors against different human cell targets by using standard 51Cr release
      cytolytic assays. A direct correlation between VL and CTL-mediated, major
      histocompatibility complex (MHC)-unrestricted lysis of primary CD4+-T-cell,
      CEM.NKR, and K562 targets was observed. CD4+-T-cell counts and duration of
      infection also correlated with MHC-unrestricted cytolytic activity. Our data
      clearly show that gammadelta CTL are abnormally expanded in the peripheral blood
      of HIV-infected patients and that the Vdelta1 subset of gammadelta T cells is the
      main effector population responsible for this type of cytolysis. The present data
      suggest that gammadelta CTL can contribute to the depletion of bystander CD4+ T
      cells in HIV-infected patients as a parallel mechanism to HIV-associated
      immunopathogenesis and hence expedite AIDS progression.

PMID- 12525620
TI  - Binding of the hepatitis C virus E2 glycoprotein to CD81 is strain specific and
      is modulated by a complex interplay between hypervariable regions 1 and 2.
AB  - The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of
      neutralizing antibodies and is presently being evaluated as an HCV vaccine
      candidate. HCV binds to human cells through the interaction of E2 with the
      tetraspanin CD81, a putative viral receptor component. We have analyzed four
      different E2 proteins from 1a and 1b viral isolates for their ability to bind to
      recombinant CD81 in vitro and to the native receptor displayed on the surface of
      Molt-4 cells. A substantial difference in binding efficiency between these E2
      variants was observed, with proteins derived from 1b subtypes showing
      significantly lower binding than the 1a protein. To elucidate the mechanism of E2
      CD81 interaction and to identify critical regions responsible for the different
      binding efficiencies of the E2 variants, several mutants were generated in E2
      protein regions predicted by computer modeling to be exposed on the protein
      surface. Functional analysis of these E2 derivatives revealed that at least two
      distinct domains are responsible for interaction with CD81. A first segment
      centered around amino acid residues 613 to 618 is essential for recognition,
      while a second element including the two hypervariable regions (HVRs) modulates
      E2 receptor binding. Binding inhibition experiments with anti-HVR monoclonal
      antibodies confirmed this mapping and supported the hypothesis that a complex
      interplay between the two HVRs of E2 is responsible for modulating receptor
      binding, possibly through intramolecular interactions. Finally, E2 proteins from
      different isolates displayed a profile of binding to human hepatic cells
      different from that observed on Molt-4 cells or isolated recombinant CD81,
      indicating that additional factors are involved in viral recognition by target
      liver cells.

PMID- 12525621
TI  - Amino acid changes within conserved region III of the herpes simplex virus and
      human cytomegalovirus DNA polymerases confer resistance to 4-oxo
      dihydroquinolines, a novel class of herpesvirus antiviral agents.
AB  - The 4-oxo-dihydroquinolines (PNU-182171 and PNU-183792) are nonnucleoside
      inhibitors of herpesvirus polymerases (R. J. Brideau et al., Antiviral Res. 54:19
      28, 2002; N. L. Oien et al., Antimicrob. Agents Chemother. 46:724-730, 2002). In
      cell culture these compounds inhibit herpes simplex virus type 1 (HSV-1), HSV-2,
      human cytomegalovirus (HCMV), varicella-zoster virus (VZV), and human herpesvirus
      8 (HHV-8) replication. HSV-1 and HSV-2 mutants resistant to these drugs were
      isolated and the resistance mutation was mapped to the DNA polymerase gene. Drug
      resistance correlated with a point mutation in conserved domain III that resulted
      in a V823A change in the HSV-1 or the equivalent amino acid in the HSV-2 DNA
      polymerase. Resistance of HCMV was also found to correlate with amino acid
      changes in conserved domain III (V823A+V824L). V823 is conserved in the DNA
      polymerases of six (HSV-1, HSV-2, HCMV, VZV, Epstein-Barr virus, and HHV-8) of
      the eight human herpesviruses; the HHV-6 and HHV-7 polymerases contain an alanine
      at this amino acid. In vitro polymerase assays demonstrated that HSV-1, HSV-2,
      HCMV, VZV, and HHV-8 polymerases were inhibited by PNU-183792, whereas the HHV-6
      polymerase was not. Changing this amino acid from valine to alanine in the HSV-1,
      HCMV, and HHV-8 polymerases alters the polymerase activity so that it is less
      sensitive to drug inhibition. In contrast, changing the equivalent amino acid in
      the HHV-6 polymerase from alanine to valine alters polymerase activity so that
      PNU-183792 inhibits this enzyme. The HSV-1, HSV-2, and HCMV drug-resistant
      mutants were not altered in their susceptibilities to nucleoside analogs; in
      fact, some of the mutants were hypersensitive to several of the drugs. These
      results support a mechanism where PNU-183792 inhibits herpesviruses by
      interacting with a binding determinant on the viral DNA polymerase that is less
      important for the binding of nucleoside analogs and deoxynucleoside
      triphosphates.

PMID- 12525622
TI  - Activation of natural killer (NK) T cells during murine cytomegalovirus infection
      enhances the antiviral response mediated by NK cells.
AB  - NK1.1+ T (NKT) cells are efficient regulators of early host responses which have
      been shown to play a role in tumor surveillance. The relevance of NKT cells in
      immune surveillance of viral infections, however, is not well understood. In this
      study, we investigated the functional relevance of NKT cells in controlling
      herpesvirus infections by using challenge with murine cytomegalovirus (MCMV) as
      the study model. This model has proven to be one of the best systems for
      evaluating the role of NK cells during virus infection. Using gene-targeted mice
      and alpha-galactosylceramide (alpha-GalCer) as an exogenous stimulator of NKT
      cells, we have analyzed the role of these cells in the immune surveillance of
      MCMV infection. Our studies in NKT-cell-deficient, T-cell receptor Jalpha281 gene
      targeted mice have established that classical NKT cells do not play a critical
      role in the early clearance of MCMV infection. Importantly, however, activation
      of NKT cells by alpha-GalCer resulted in reduced viral replication in visceral
      organs. Depletion studies, coupled with analysis of gene-targeted mice lacking
      perforin and gamma interferon (IFN-gamma), have revealed that the antiviral
      effects of alpha-GalCer involve NK cells and have clearly demonstrated that the
      antiviral activity of alpha-GalCer, unlike the antitumor one, is critically
      dependent on both perforin and IFN-gamma.

PMID- 12525623
TI  - Conditional replication of duck hepatitis B virus in hepatoma cells.
AB  - To facilitate investigations of replication and host cell interactions in the
      hepadnavirus system, we have developed cell lines permitting the conditional
      replication of duck hepatitis B virus (DHBV). With the help of this system, we
      devised conditions for core particle isolation that preserve replicase activity,
      which was not found in previous preparations. Investigations of the stability of
      viral DNA intermediates indicated that both encapsidated DNA and covalently
      closed circular DNA (cccDNA) were turned over independently of cell division.
      Moreover, we showed that alpha interferon reduced the accumulation of RNA
      containing viral particles. The availability of a synchronized replication system
      will permit the biochemical analysis of individual steps of the viral replication
      cycle, including the mechanism and regulation of cccDNA formation.

PMID- 12525624
TI  - A mutant form of the tax protein of bovine leukemia virus (BLV), with enhanced
      transactivation activity, increases expression and propagation of BLV in vitro
      but not in vivo.
AB  - In a previous study, we identified an interesting mutant form of the Tax protein
      of bovine leukemia virus (BLV), designated D247G. This mutant protein strongly
      transactivated the long terminal repeat of BLV and was also able to transactivate
      the cellular proto-oncogene c-fos. This finding suggested that BLV that encode
      the mutant protein might propagate and induce lymphoma more efficiently than wild
      type BLV. To characterize the effects of the strong transactivation activity of
      the mutant Tax protein, we constructed an infectious molecular clone of BLV that
      encoded D247G and examined the replication and propagation of the virus in vitro
      and in vivo. Cultured cells were transfected with the wild-type and mutant BLV,
      and then levels of viral proteins and particles and the propagation of viruses
      were compared. As expected, in vitro, mutant BLV produced more viral proteins and
      particles and was transmitted very effectively. We injected the wild-type and
      mutant BLV into sheep, which are easily infected with BLV, and monitored the
      proportion of BLV-positive cells in the blood and the expression of BLV RNA for
      28 weeks. By contrast to the results of our analyses in vitro, we found no
      significant difference in the viral load or the expression of viral RNA between
      sheep inoculated with wild-type or mutant BLV. Our observations indicate that the
      mutant D247G Tax protein does not enhance the expansion of BLV and that there
      might be a dominant mechanism for regulation of the expression of BLV in vivo.

PMID- 12525626
TI  - Independent segregation of human immunodeficiency virus type 1 Gag protein
      complexes and lipid rafts.
AB  - Formation of human immunodeficiency virus type 1 (HIV-1) particles takes place at
      the plasma membrane of cells and is directed by the Pr55Gag polyprotein. A
      functional assembly domain (the M domain) within the N-terminal portion of
      Pr55Gag mediates the interaction of Gag with cellular membranes. However, the
      determinants that provide specificity for assembly on the plasma membrane, as
      opposed to intracellular membranes, have not been identified. Recently, it was
      reported that Pr55Gag interacts with lipid raft microdomains of the plasma
      membrane. We sought to identify the domains within Pr55Gag that contribute to
      lipid raft association of Gag. Here we demonstrate that the I domain is required
      for interaction with detergent-resistant membrane fractions (DRMs). Mutation of
      key I-domain residues or loss of myristylation abrogated the association of Gag
      with DRMs. Thus, the I domain and the M domain combine to mediate Gag-lipid raft
      interactions as defined by these biochemical criteria. However, Gag protein
      complexes defined by flotation studies were much denser than classical lipid
      rafts, failed to incorporate classical lipid raft marker proteins, and were not
      disrupted by cholesterol extraction. Large sheets of Gag protein were identified
      in DRM fractions upon examination by electron microscopy. These results indicate
      that HIV-1 Pr55Gag forms detergent-resistant complexes at the cellular periphery
      that are distinct from lipid raft microdomains.

PMID- 12525625
TI  - Identification and characterization of an adeno-associated virus integration site
      in CV-1 cells from the African green monkey.
AB  - Adeno-associated virus (AAV) is a classification given to a group of
      nonpathogenic, single-stranded DNA viruses known to reside latently in primates.
      During latency in humans, AAV type 2 (AAV2) preferentially integrates at a site
      on chromosome 19q13.3ter by targeting a sequence composed of an AAV Rep binding
      element (RBE), a spacer, and a nicking site. Here, we report the DNA sequence of
      an African green monkey AAV integration site isolated from CV-1 cells. Overall,
      it has 98% homology to the analogous human site, including identical spacer and
      nicking sequences. However, the simian RBE is expanded, having five perfect
      directly repeated GAGC tetramers. We carried out a number of in vitro and in vivo
      assays to determine the effect of this expanded RBE sequence on the Rep-RBE
      interaction and AAV targeted integration. Using electromobility shift assays it
      was demonstrated that AAV4 Rep68 bound the expanded RBE with a sixfold-greater
      affinity than the human RBE. To determine the basis for the affinity increase,
      DNase I protection and methylation interference (MI) assays were performed.
      Comparison of footprints on both the human and simian RBEs revealed nearly
      identical protection; however, MI analysis suggested greater interaction with the
      guanine nucleotides of the expanded RBE, thus providing a biochemical basis for
      the increased binding activity. In vivo, integration targeted to the simian RBE
      was demonstrated by PCR analysis of latently infected Cos-7 cells. Interestingly,
      the frequency of site-specific integration was twofold greater in Cos-7 cells
      than in HeLa cells. Overall, these experiments establish that the simian RBE,
      identified in CV-1 cells, functions analogously to the human RBE and provide
      further evidence for a developing model that proposes individual roles for the
      RBE and the spacer and nicking site elements.

PMID- 12525627
TI  - HLA class II polymorphisms and susceptibility to recurrent respiratory
      papillomatosis.
AB  - Recurrent respiratory papillomatosis (RRP) is characterised by multiple laryngeal
      papillomas. Left untreated, the lesions enlarge, spread, and endanger the airway.
      Medical treatments are unsatisfactory, and repeated surgery remains the mainstay
      of therapy. RRP is caused by human papillomavirus (HPV) infection. However, since
      oral HPV infection is common and RRP is rare, other host and/or viral factors may
      contribute to pathogenesis. In an attempt to identify such factors, we have
      investigated 60 patients. The patients were HLA class I, II, and tumor necrosis
      factor TNF typed by sequence-specific primer PCR, and the results compared to
      those for 554 healthy controls by using Fisher's exact test. Peripheral blood
      mononuclear cell proliferative responses of 25 controls and 10 patients to HPV-11
      L1 virus-like particles (VLP) were compared. Short-term VLP-specific T-cell lines
      were established, and recognition of L1 was analyzed. Finally, the L1 open
      reading frames of HPV isolates from four patients were sequenced. Susceptibility
      to RRP was associated with HLA DRB1*0301 (33 of 60 patients versus 136 of 554
      controls, P < 0.0001). The three most severely affected patients were homozygous
      for this allele. A range of T-cell proliferative responses to HPV-11 VLP were
      observed in DRB1*0301-positive healthy donors which were comparable to those in
      DRB1*0301-negative controls. Individuals with juvenile-onset RRP also mounted a
      range of VLP responses, and their magnitude was negatively correlated with the
      clinical staging score (P = 0.012 by the Spearman rank correlation). DRB1*0301
      positive patients who responded to L1 recognized the same epitope as did matched
      controls and produced similar cytokines. Sequencing of clinical isolates excluded
      the possibility that nonresponsiveness was the result of mutation(s) in L1.

PMID- 12525628
TI  - Impact of highly active antiretroviral therapy and immunologic status on
      hepatitis C virus quasispecies diversity in human immunodeficiency
      virus/hepatitis C virus-coinfected patients.
AB  - This study analyzes the effect of highly active antiretroviral therapy (HAART),
      and thus immunologic status, on hepatitis C virus (HCV) load and quasispecies
      diversity in patients coinfected with the human immunodeficiency virus (HIV) and
      HCV. Three cohorts of coinfected patients were analyzed retrospectively over a
      period of 7 to 10 months: group A was antiretroviral drug naive at baseline and
      then on HAART for the remainder of the study, group B did not receive
      antiretroviral therapy at any point, and group C was on HAART for the entire
      study. HCV quasispecies diversity was analyzed by sequencing hypervariable region
      1. In a longitudinal analysis, there was no significant change from baseline in
      any immunologic, virologic, or quasispecies parameter in any of the three groups.
      However, in comparison to groups A and B, group C had significantly higher CD4+-
      and CD8+-cell counts, a trend toward a higher HCV load, and significantly
      increased number of HCV clones, entropy, genetic distance, and ratio of
      nonsynonymous substitutions per nonsynonymous site to synonymous substitutions
      per synonymous site (Ka/Ks). In addition, CD4+-cell count was positively
      correlated with HCV load, genetic distance, and Ka. Interestingly, patients
      infected with HCV genotype 2 or 3 had a significantly higher CD4+-cell count, HCV
      load, genetic distance, and Ka/Ks than those infected with genotype 1. These
      results suggest that there is no immediate effect of HAART on HCV but that, with
      prolonged HAART, immune restoration results in an increase in HCV load and
      quasispecies diversity.

PMID- 12525629
TI  - Evidence for mixed membrane topology of the newcastle disease virus fusion
      protein.
AB  - The synthesis of the Newcastle disease virus (NDV) fusion (F) protein in a cell
      free protein-synthesizing system containing membranes was characterized. The
      membrane-associated products were in at least two different topological forms
      with respect to the membranes. The properties of one form were consistent with
      the expected membrane insertion as a classical type 1 glycoprotein. This form of
      the protein was fully glycosylated, and sequences amino terminal to the
      transmembrane domain were protected from protease digestion by the membranes. The
      second form of membrane-associated F protein was partially glycosylated and
      partially protected from protease digestion by the membranes. Protease digestion
      resulted in a 23-kDa protease-protected polypeptide derived from F2 sequences and
      sequences from the amino-terminal end of the F1 domain. Furthermore, a 10-kDa
      polypeptide derived from the cytoplasmic domain (CT) was also protected from
      protease digestion by the membranes. Protease resistance of the 23- and 10-kDa
      polypeptides suggested that this second form of F protein inserted in membranes
      in a polytopic conformation with both the amino-terminal end and the carboxyl
      terminal end translocated across membranes. To determine if this second form of
      the fusion protein could be found in cells expressing the F protein, two
      different approaches were taken. A polypeptide with the size of the partially
      translocated F protein was detected by Western analysis of proteins in total-cell
      extracts of NDV strain B1 (avirulent)-infected Cos-7 cells. Using antibodies
      raised against a peptide with sequences from the cytoplasmic domain, CT sequences
      were detected on surfaces of F protein-expressing Cos-7 cells by
      immunofluorescence and by flow cytometry. This antibody also inhibited the fusion
      of red blood cells to cells expressing F and HN proteins. These results suggest
      that NDV F protein made both in a cell-free system and in Cos-7 cells may exist
      in two topological forms with respect to membranes and that the second form of
      the protein may be involved in cell-cell fusion.

PMID- 12525630
TI  - New hepatitis B virus of cranes that has an unexpected broad host range.
AB  - All hepadnaviruses known so far have a very limited host range, restricted to
      their natural hosts and a few closely related species. This is thought to be due
      mainly to sequence divergence in the large envelope protein and species-specific
      differences in host components essential for virus propagation. Here we report an
      infection of cranes with a novel hepadnavirus, designated CHBV, that has an
      unexpectedly broad host range and is only distantly evolutionarily related to
      avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA
      as well a sequencing of cloned viral genomes revealed that CHBV is most closely
      related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and
      slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically,
      cranes are very distant from geese and ducks and are most closely related to
      herons and storks. Naturally occurring hepadnaviruses in the last two species are
      highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so
      only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced
      from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV
      did. This is the first report of a rather broad host range of an avihepadnavirus.
      Our data imply either usage of similar or identical entry pathways and receptors
      by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent
      evolution of the host genomes and cellular components required for virus
      propagation.

PMID- 12525631
TI  - Two retroviral entry pathways distinguished by lipid raft association of the
      viral receptor and differences in viral infectivity.
AB  - The receptor "priming" model for entry of the retrovirus avian sarcoma and
      leukosis virus (ASLV) predicts that upon binding cell surface receptors, virions
      are endocytosed and trafficked to acidic endosomes where fusion occurs. To test
      this model directly, we have now followed subgroup A ASLV (ASLV-A) virions
      entering cells via either the transmembrane (TVA950) or glycophosphatidylinositol
      (GPI)-anchored (TVA800) forms of the cellular receptor. Our results suggest that
      viruses entering via these two forms of receptor are subjected to different
      intracellular fates, perhaps due to use of different endocytic trafficking
      pathways to access acidic fusion compartments. Kinetic analyses demonstrated that
      virus bound to TVA800 was taken up from the cell surface more slowly but then
      trafficked to the site of fusion more quickly than that entering via TVA950.
      Furthermore, transiently arresting virions within putative fusion compartments
      with NH4Cl led to a substantially greater decrease in the infectivity of virions
      using TVA950 than with those using TVA800. The increased infectivity of virions
      using TVA800 correlated with the localization of this receptor to lipid rafts,
      since this effect was abolished by pharmacological disruption of lipid rafts.
      Together these results suggest that, in the presence of NH4Cl, virus bound to the
      GPI-anchored receptor may utilize a lipid raft-dependent pathway to accumulate
      within a fusion compartment where it is more stable than if it enters via the
      transmembrane receptor. The TVA800/ASLV-A system should prove useful for the
      molecular analysis of lipid raft-dependent endocytosis and may provide a tool for
      the biochemical dissection of the poorly understood uncoating step of retroviral
      replication.

PMID- 12525632
TI  - Replication of human immunodeficiency viruses engineered with heterologous Tat
      transactivation response element interactions.
AB  - Human immunodeficiency viruses (HIVs) and the related bovine lentiviruses bovine
      immunodeficiency virus (BIV) and Jembrana disease virus (JDV) utilize the viral
      Tat protein to activate viral transcription. The arginine-rich RNA-binding
      domains of the Tat proteins bind to their cognate transactivation response
      element (TAR) RNA hairpins located at the 5' ends of the viral mRNAs, resulting
      in enhanced processivity of RNA polymerase II. It has previously been shown that
      HIV type 1 (HIV-1) Tat requires the cellular cyclin T1 protein for high-affinity
      RNA binding whereas BIV Tat and JDV Tat bind with high affinity on their own and
      adopt distinct beta-hairpin conformations when complexed to RNA. Here we have
      engineered the BIV and JDV Tat-TAR interactions into HIV-1 and show that the
      heterologous interactions support viral replication, correlating well with their
      RNA-binding affinities. Viruses engineered with a variant TAR able to bind all
      three Tat proteins replicate efficiently with any of the proteins. In one virus
      containing a noncognate Tat-TAR pair that neither interacts nor efficiently
      replicates (HIV-1 TAR and BIV Tat), viral revertants were isolated in which TAR
      had become mutated to generate a functional BIV Tat binding site. Our results
      support the view that incremental changes to TAR structure can provide routes for
      evolving new Tat-TAR complexes while maintaining active viral replication.

PMID- 12525633
TI  - Molecular and functional analysis of an interferon gene from the zebrafish, Danio
      rerio.
AB  - The interferon (IFN) family consisting of alpha IFN (IFN-alpha), IFN-beta, IFN
      omega, IFN-delta, IFN-kappa, and IFN-tau is a large group of cytokines involved
      in the innate immune response against various microorganisms. Genes for IFN have
      been cloned from a variety of mammalian and avian species; however, IFN genes
      from lower-order vertebrates have not been forthcoming. Here, we report the
      cloning and characterization of the IFN gene from the zebrafish, Danio rerio.
      Zebrafish IFN (zfIFN) is 185 amino acids in length, with the first 22 amino acids
      representing a putative signal peptide. Treatment with the known IFN inducer
      polyinosinic acid-polycytidylic acid (poly[I]-poly[C]) resulted in an increase in
      zfIFN mRNA transcripts. zfIFN was also able to activate the IFN-inducible Mx
      promoter when cotransfected with a plasmid containing the zebrafish Mx promoter
      upstream of a luciferase reporter gene. To demonstrate antiviral activity,
      zebrafish cells were transfected with zfIFN and challenged with a fish
      rhabdovirus. A 36% reduction in plaque number was seen in zfIFN-transfected
      cells, compared to cells transfected with a control vector. Phylogenetic analysis
      has shown zfIFN to be approximately equally divergent from avian and mammalian
      IFN, consistent with its origin from an IFN present in the most recent common
      ancestor of these divergent lineages. A putative IFN from puffer, Fugu rubripes,
      was also found when zfIFN was used to search the fugu genome database,
      demonstrating that zfIFN can be used to find additional fish IFN genes. These
      results demonstrate that zebrafish can be used as an effective model for studying
      innate immunity and immune response to infectious disease.

PMID- 12525634
TI  - Multiple amino acid residues within the rabbit prion protein inhibit formation of
      its abnormal isoform.
AB  - Transmissible spongiform encephalopathies (TSEs) are neurological diseases that
      are associated with the conversion of the normal host-encoded prion protein (PrP
      sen) to an abnormal protease-resistant form, PrP-res. Transmission of the TSE
      agent from one species to another is usually inefficient and accompanied by a
      prolonged incubation time. Species barriers to infection by the TSE agent are of
      particular importance given the apparent transmission of bovine spongiform
      encephalopathy to humans. Among the few animal species that appear to be
      resistant to infection by the TSE agent are rabbits. They survive challenge with
      the human kuru and Creutzfeldt-Jakob agents as well as with scrapie agent
      isolated from sheep or mice. Species barriers to the TSE agent are strongly
      influenced by the PrP amino acid sequence of both the donor and recipient
      animals. Here we show that rabbit PrP-sen does not form PrP-res in murine tissue
      culture cells persistently infected with the mouse-adapted scrapie agent. Unlike
      other TSE species barriers that have been studied, critical amino acid residues
      that inhibit PrP-res formation are located throughout the rabbit PrP sequence.
      Our results suggest that the resistance of rabbits to infection by the TSE agent
      is due to multiple rabbit PrP-specific amino acid residues that result in a PrP
      structure that is unable to refold to the abnormal isoform associated with
      disease.

PMID- 12525635
TI  - Importance of basic residues in binding of rous sarcoma virus nucleocapsid to the
      RNA packaging signal.
AB  - In the context of the Rous sarcoma virus Gag polyprotein, only the nucleocapsid
      (NC) domain is required to mediate the specificity of genomic RNA packaging. We
      have previously showed that the Saccharomyces cerevisiae three-hybrid system
      provides a rapid genetic assay to analyze the RNA and protein components of the
      avian retroviral RNA-Gag interactions necessary for specific encapsidation. In
      this study, using both site-directed mutagenesis and in vivo random screening in
      the yeast three-hybrid binding assay, we have examined the amino acids in NC
      required for genomic RNA binding. We found that we could delete either of the two
      Cys-His boxes without greatly abrogating either RNA binding or packaging,
      although the two Cys-His boxes are likely to be required for efficient viral
      assembly and release. In contrast, substitutions for the Zn-coordinating residues
      within the boxes did prevent RNA binding, suggesting changes in the overall
      conformation of the protein. In the basic region between the two Cys-His boxes,
      three positively charged residues, as well as basic residues flanking the two
      boxes, were necessary for both binding and packaging. Our results suggest that
      the stretches of positively charged residues within NC that need to be in a
      proper conformation appear to be responsible for selective recognition and
      binding to the packaging signal (Psi)-containing RNAs.

PMID- 12525636
TI  - Human papillomavirus type 16 E2 protein has no effect on transcription from
      episomal viral DNA.
AB  - The human papillomavirus (HPV) E2 protein plays an important role in viral DNA
      replication. Many studies with high-risk HPVs have demonstrated that the E2
      protein can also repress transcription of the E6 and E7 oncogenes. This
      conclusion, based on experiments carried out with cervical cancer cells bearing
      integrated HPV genomes, is currently assumed to be applicable to the normal HPV
      life cycle, in which the viral genomes are episomal. Here, we have tested
      experimentally whether this assumption is correct. We made use of a pair of
      isogenic cell lines, W12 and S12. W12 cells contain episomal HPV16 genomes,
      whereas S12 cells, which are derived from the W12 line, contain HPV DNA as
      integrated copies. When we expressed E2 in S12 cells, we observed strong
      repression of E6 and E7 transcription. In contrast, no effect of E2 on the
      transcription of these genes was detected in W12 cells. While integration of the
      viral genome into the host DNA contributes to the difference between W12 and S12
      cells, integration by itself is not sufficient to explain this difference.
      Instead, the chromatin structure in the region of the E6 and E7 promoter (p97),
      which we show to be very different in these two cell lines, is likely to be the
      cause of the different responsiveness of p97 to the E2 protein. Experiments with
      the histone deacetylase inhibitor trichostatin A (TSA) indicated that the
      episomal HPV16 DNA is in a relatively inaccessible state prior to TSA treatment.
      Our results, together with those of others, suggest that any effect of the E2
      protein on the expression of the E6 and E7 genes during the normal viral life
      cycle is of secondary importance compared to the function of E2 in replication.

PMID- 12525637
TI  - Hepatitis C virus RNA synthesis in a cell-free system isolated from replicon
      containing hepatoma cells.
AB  - A number of hepatitis C virus (HCV) proteins, including NS5B, the RNA-dependent
      RNA polymerase, were detected in membrane fractions from Huh7 cells containing
      autonomously replicating HCV RNA replicons. These membrane fractions were used in
      a cell-free system for the analysis of HCV RNA replication. Initial
      characterization revealed a reaction in which the production of replicon RNA
      increased over time at temperatures ranging from 25 to 40 degrees C. Heparin
      sensitivity and nucleotide starvation experiments suggested that de novo
      initiation was occurring in this system. Both Mn2+ and Mg2+ cations could be used
      in the reaction; however, concentrations of Mn2+ greater than 1 mM were
      inhibitory. Compounds shown to inhibit recombinant NS3 and NS5B activity in vitro
      were found to inhibit RNA synthesis in the cell-free system. This system should
      be useful for biochemical analysis of HCV RNA synthesis by a multisubunit
      membrane-associated replicase and for evaluating potential antiviral agents
      identified in biochemical or cell-based screens.

PMID- 12525638
TI  - A subpopulation of tegument protein vhs localizes to detergent-insoluble lipid
      rafts in herpes simplex virus-infected cells.
AB  - Virion host shutoff (vhs) is a 58-kDa protein encoded by the UL41 gene of herpes
      simplex virus (HSV). vhs resides within the tegument of HSV, enters the cell
      cytoplasm at infection, and destabilizes host cell and viral mRNA. Late in
      infection, vhs must be assembled into the tegument of progeny virions, a poorly
      understood process. Using an anti-vhs antiserum and Western blotting of total
      cell or cytoplasmic extracts, we found that vhs is largely insoluble in HSV
      infected cells, even in the presence of high levels of salt and the detergent
      Triton X-100. Furthermore, a subpopulation of vhs appears to be associated with
      detergent-insoluble lipid rafts and this raft population is enriched in a
      cytoplasmic fraction which contains assembling and mature HSV particles. Our data
      raise the possibility that HSV tegument polypeptides associate with membrane
      rafts, in common with the matrix proteins of a number of other viruses.

PMID- 12525639
TI  - Enhancement of antibodies to the human immunodeficiency virus type 1 envelope by
      using the molecular adjuvant C3d.
AB  - DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency
      virus have been relatively ineffective at generating high-titer, long-lasting,
      neutralizing antibodies in a variety of animal models. In this study, the murine
      and human homologues of the complement component, C3d, were used in a DNA vaccine
      to enhance the titers of antibody to Env. Initially, plasmids expressing a
      secreted form of Env (sgp120) fused to one, two, or three copies of the murine
      homologue of C3d (mC3d) were constructed. Mice were inoculated with four
      vaccinations of DNA or two DNA vaccinations, followed by two boosts of affinity
      purified gp120 protein. Analyses of titers demonstrated that multiple copies of
      mC3d coupled to sgp120 induced long-lasting, high-titer anti-Env antibody.
      Priming mice with sgp120-mC3d-DNA, followed by inoculation of purified gp120
      protein, elicited the strongest antibody titers; however, the avidity maturation
      of the antibody was accelerated in the mice inoculated with sgp120-mC3d(3)-DNA.
      In addition, DNAs expressing sgp120 fused to three copies of the human homologue
      of C3d (hC3d(3)) efficiently enhanced the anti-Env antibody in rabbits. Lastly,
      antisera from both mice and rabbits vaccinated with DNA expressing sgp120-C3d(3)
      elicited higher titers of neutralizing antibody than did nonfused forms of Env.
      These results indicate that C3d, conjugated to sgp120, enhances the antibody
      responses to Env compared to non-C3d fused forms of Env, and this approach may be
      one way to overcome the poor ability of DNA vaccines to generate antibodies to
      Env.

PMID- 12525640
TI  - Genome-based identification of cancer genes by proviral tagging in mouse
      retrovirus-induced T-cell lymphomas.
AB  - The identification of tumor-inducing genes is a driving force for elucidating the
      molecular mechanisms underlying cancer. Many retroviruses induce tumors by
      insertion of viral DNA adjacent to cellular oncogenes, resulting in altered
      expression and/or structure of the encoded proteins. The availability of the
      mouse genome sequence now allows analysis of retroviral common integration sites
      in murine tumors to be used as a genetic screen for identification of large
      numbers of candidate cancer genes. By positioning the sequences of inverse PCR
      amplified, virus-host junction fragments within the mouse genome, 19 target genes
      were identified in T-cell lymphomas induced by the retrovirus SL3-3. The
      candidate cancer genes included transcription factors (Fos, Gfi1, Lef1, Myb, Myc,
      Runx3, and Sox3), all three D cyclins, Ras signaling pathway components
      (Rras2/TC21 and Rasgrp1), and Cmkbr7/CCR7. The most frequent target was Rras2.
      Insertions as far as 57 kb away from the transcribed portion were associated with
      substantially increased transcription of Rras2, and no coding sequence mutations,
      including those typically involved in Ras activation, were detected. These
      studies demonstrate the power of genome-based analysis of retroviral insertion
      sites for cancer gene discovery, identify several new genes worth examining for a
      role in human cancer, and implicate the pathways in which those genes act in
      lymphomagenesis. They also provide strong genetic evidence that overexpression of
      unmutated Rras2 contributes to tumorigenesis, thus suggesting that it may also do
      so if it is inappropriately expressed in human tumors.

PMID- 12525641
TI  - Depletion of Wee-1 kinase is necessary for both human immunodeficiency virus type
      1 Vpr- and gamma irradiation-induced apoptosis.
AB  - Human immunodeficiency virus (HIV) protein R (Vpr) induces G2 arrest, and
      prolonged G2 arrest leads to apoptosis. We find that in HeLa cells the cell cycle
      regulatory kinase, Wee-1, is depleted following prolonged G2 arrest induced by
      Vpr. Of note, small interfering RNAs directed to Wee-1 triggered apoptosis,
      suggesting a direct role for Wee-1 in apoptosis. In support of this hypothesis,
      overexpression of Wee-1 suppressed Vpr-mediated apoptosis. Importantly, similar
      results were observed with cells induced to undergo apoptosis gamma irradiation.
      Thus, Wee-1 may serve as a key regulator of both HIV type 1 Vpr- and gamma
      irradiation-mediated apoptosis and possibly serve as a general regulator linking
      the cell cycle to some pathways of apoptosis.

PMID- 12525642
TI  - Influence of reverse transcriptase variants, drugs, and Vpr on human
      immunodeficiency virus type 1 mutant frequencies.
AB  - The evolution of drug resistance is a major complication of human
      immunodeficiency virus type 1 (HIV-1) chemotherapy. HIV-1 reverse transcriptase
      (RT) is a major target of antiretroviral therapy and ultimately the target of
      drug resistance mutations. Previous studies have indicated that drug-resistant
      HIV-1 RTs can alter HIV-1 mutant frequencies. In this study, we have tested a
      panel of HIV-1 RT variants for their ability to influence virus mutant
      frequencies. The RT variants tested included drug-resistant RT variants as well
      as other variants analyzed in enzyme fidelity studies with the lacZalpha gene as
      a mutation target and/or implicated as being important for enzyme fidelity by
      structural studies. Combinations of mutations that alone had a statistically
      significant influence on virus mutant frequencies resulted in different mutant
      frequency phenotypes. Furthermore, when virus replication occurred in the
      presence of drugs [e.g., 3'-azido-3'-deoxythymidine, (-)2/,3'-dideoxy-3'
      thiacytidine, hydroxyurea, thymidine, or thioguanine] with selected RT variants,
      virus mutant frequencies increased. Similarly, Vpr variants deficient for binding
      to the uracil DNA glycosylase repair enzyme were observed to influence HIV-1
      virus mutant frequencies when tested alone or in combination with RT variants. In
      summary, these observations indicate that HIV-1 mutant frequencies can
      significantly change by single amino acid substitutions in RT and that these
      effects can be altered by additional mutations in RT, by drugs, and/or by
      expression of Vpr variants. Such altered virus mutant frequencies could impact
      HIV-1 dynamics and evolution in small population sizes.

PMID- 12525643
TI  - Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)
      specific T-cell responses directed against the entire expressed HIV-1 genome
      demonstrate broadly directed responses, but no correlation to viral load.
AB  - Cellular immune responses play a critical role in the control of human
      immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at
      the single-epitope level has not been comprehensively assessed. We therefore
      screened peripheral blood mononuclear cells (PBMC) from 57 individuals at
      different stages of HIV-1 infection for virus-specific T-cell responses using a
      matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a
      gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell
      responses were detectable in all study subjects, with a median of 14 individual
      epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein
      subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope
      density and were also the most frequently recognized HIV-1 proteins. The total
      magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming
      cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the
      number of epitopic regions targeted, the protein subunits recognized, and the
      total magnitude of HIV-1-specific responses varied significantly among the tested
      individuals, with the strongest and broadest responses detectable in individuals
      with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of
      the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load.
      We conclude that a peptide matrix-based Elispot assay allows for rapid,
      sensitive, specific, and efficient assessment of cellular immune responses
      directed against the entire expressed HIV-1 genome. These data also suggest that
      the impact of T-cell responses on control of viral replication cannot be
      explained by the mere quantification of the magnitude and breadth of the CD8+-T
      cell response, even if a comprehensive pan-genome screening approach is applied.

PMID- 12525644
TI  - Antibody-mediated targeting of an adenovirus vector modified to contain a
      synthetic immunoglobulin g-binding domain in the capsid.
AB  - Adenovirus vectors have been targeted to different cell types by genetic
      modification of the capsid or by using recombinant or chemically engineered
      adaptor molecules. However, both genetic capsid modifications and bridging
      adaptors have to be specifically tailored for each particular targeting
      situation. Here, we present an efficient and versatile strategy allowing the
      direct use of monoclonal antibodies against cell surface antigens for targeting
      of adenovirus vectors. A synthetic 33-amino-acid immunoglobulin G (IgG)-binding
      domain (Z33) derived from staphylococcal protein A was inserted into the
      adenovirus fiber protein. The fiber retained the ability to assemble into
      trimers, bound IgG with high affinity (Kd = 2.4 nM), and was incorporated into
      vector particles. The transduction efficiency of the Z33-modified adenovirus
      vector in epidermal growth factor receptor (EGFR)-expressing cells was strongly
      and dose-dependently enhanced by combination with an EGFR-specific monoclonal
      antibody. The antibody-mediated increase in cellular transduction was abolished
      in the presence of competing protein A. In targeting experiments with
      differentiated primary human muscle cells, up to a 77-fold increase in reporter
      gene transfer was achieved by preincubation of the vector with monoclonal
      antibodies directed against neuronal cell adhesion molecule or integrin alpha(7),
      respectively. The IgG-binding adenovirus vector holds promise for directed gene
      transfer to a wide variety of cell types by simply changing the target-specific
      antibody.

PMID- 12525646
TI  - Replication of Carnation Italian ringspot virus defective interfering RNA in
      Saccharomyces cerevisiae.
AB  - Two plasmids from which the sequences coding for the 36- and 95-kDa proteins of
      Carnation Italian ringspot virus (CIRV) could be transcribed in vivo in the yeast
      Saccharomyces cerevisiae under the control of the ADH1 promoter and terminator
      were constructed. The two proteins, which constitute the viral replicase, were
      correctly translated and integrated into membranes of the yeast cells. An
      additional plasmid was introduced in yeasts expressing the CIRV replicase, from
      which a defective interfering (DI) RNA (DI-7 RNA) could be transcribed under the
      control of the GAL1 promoter and terminated by the Tobacco ringspot virus
      satellite ribozyme, which cleaved 19 nucleotides downstream of the 3' end of DI
      RNA. The DI-7 RNA transcripts were amplified by the viral replicase as
      demonstrated by the restoration of the authentic 3' end, the requirement of a
      specific cis-acting signal at this terminus, the preferential accumulation of
      molecules with the authentic 5' terminus (AGAAA), the synthesis of head-to-tail
      dimers, the presence of negative strands, and the incorporation of 5-bromo-UTP.
      Additionally, transformation with a dimeric construct of DI-7 RNA led to the
      synthesis of monomers, mimicking the activity of the viral replicase in plant
      cells.

PMID- 12525645
TI  - Exonic splicing enhancer-dependent selection of the bovine papillomavirus type 1
      nucleotide 3225 3' splice site can be rescued in a cell lacking splicing factor
      ASF/SF2 through activation of the phosphatidylinositol 3-kinase/Akt pathway.
AB  - Bovine papillomavirus type 1 (BPV-1) late pre-mRNAs are spliced in keratinocytes
      in a differentiation-specific manner: the late leader 5' splice site
      alternatively splices to a proximal 3' splice site (at nucleotide 3225) to
      express L2 or to a distal 3' splice site (at nucleotide 3605) to express L1. Two
      exonic splicing enhancers, each containing two ASF/SF2 (alternative splicing
      factor/splicing factor 2) binding sites, are located between the two 3' splice
      sites and have been identified as regulating alternative 3' splice site usage.
      The present report demonstrates for the first time that ASF/SF2 is required under
      physiological conditions for the expression of BPV-1 late RNAs and for selection
      of the proximal 3' splice site for BPV-1 RNA splicing in DT40-ASF cells, a
      genetically engineered chicken B-cell line that expresses only human ASF/SF2
      controlled by a tetracycline-repressible promoter. Depletion of ASF/SF2 from the
      cells by tetracycline greatly decreased viral RNA expression and RNA splicing at
      the proximal 3' splice site while increasing use of the distal 3' splice site in
      the remaining viral RNAs. Activation of cells lacking ASF/SF2 through anti
      immunoglobulin M-B-cell receptor cross-linking rescued viral RNA expression and
      splicing at the proximal 3' splice site and enhanced Akt phosphorylation and
      expression of the phosphorylated serine/arginine-rich (SR) proteins SRp30s
      (especially SC35) and SRp40. Treatment with wortmannin, a specific
      phosphatidylinositol 3-kinase/Akt kinase inhibitor, completely blocked the
      activation-induced activities. ASF/SF2 thus plays an important role in viral RNA
      expression and splicing at the proximal 3' splice site, but activation-rescued
      viral RNA expression and splicing in ASF/SF2-depleted cells is mediated through
      the phosphatidylinositol 3-kinase/Akt pathway and is associated with the enhanced
      expression of other SR proteins.

PMID- 12525647
TI  - Human immunodeficiency virus type 1 Nef-mediated downregulation of CD4 correlates
      with Nef enhancement of viral pathogenesis.
AB  - The nef gene products encoded by human immunodeficiency virus type 1 (HIV-1) and
      simian immunodeficiency virus type 1 (SIV-1) increase viral loads in infected
      hosts and accelerate clinical progression to AIDS. Nef exhibits a spectrum of
      biological activities, including the ability to downregulate surface expression
      of CD4 and major histocompatibility complex (MHC) class I antigens, to alter the
      state of T-cell activation, and to enhance the infectivity of viral particles. To
      determine which of these in vitro functions most closely correlates with the
      pathogenic effects of Nef in vivo, we constructed recombinant HIV-1 NL4-3 viruses
      carrying mutations within the nef gene that selectively impair these functions.
      These mutant viruses were evaluated for pathogenic potential in severe combined
      immunodeficiency (SCID) mice implanted with human fetal thymus and liver (SCID-hu
      Thy/Liv mice), in which virus-mediated depletion of thymocytes is known to be Nef
      dependent. Disruption of the polyproline type II helix (Pxx)4 within Nef
      (required for binding of Hck and p21-activated kinase-like kinases,
      downregulation of MHC class I, and enhancement of HIV-1 infectivity in vitro but
      dispensable for CD4 downregulation) did not impair thymocyte depletion in virus
      infected Thy/Liv human thymus implants. Conversely, three separate point
      mutations in Nef that compromised its ability to downregulate CD4 attenuated
      thymocyte depletion while not diminishing viral replication. These findings
      indicate that the functional ability of Nef to downregulate CD4 and not MHC class
      I downregulation, Hck or PAK binding, or (Pxx)4-associated enhancement of
      infectivity most closely correlates with Nef-mediated enhancement of HIV-1
      pathogenicity in vivo. Nef-mediated CD4 downregulation merits consideration as a
      new target for the development of small-molecule inhibitors.

PMID- 12525648
TI  - Establishment of B-cell lymphoma cell lines persistently infected with hepatitis
      C virus in vivo and in vitro: the apoptotic effects of virus infection.
AB  - Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis,
      and hepatocellular carcinoma. Studies of HCV replication and pathogenesis have so
      far been hampered by the lack of an efficient tissue culture system for
      propagating HCV in vitro. Although HCV is primarily a hepatotropic virus, an
      increasing body of evidence suggests that HCV also replicates in extrahepatic
      tissues in natural infection. In this study, we established a B-cell line (SB)
      from an HCV-infected non-Hodgkin's B-cell lymphoma. HCV RNA and proteins were
      detectable by RNase protection assay and immunoblotting. The cell line
      continuously produces infectious HCV virions in culture. The virus particles
      produced from the culture had a buoyant density of 1.13 to 1.15 g/ml in sucrose
      and could infect primary human hepatocytes, peripheral blood mononuclear cells
      (PBMCs), and an established B-cell line (Raji cells) in vitro. The virus from SB
      cells belongs to genotype 2b. Single-stranded conformational polymorphism and
      sequence analysis of the viral RNA quasispecies indicated that the virus present
      in SB cells most likely originated from the patient's spleen and had an HCV RNA
      quasispecies pattern distinct from that in the serum. The virus production from
      the infected primary hepatocytes showed cyclic variations. In addition, we have
      succeeded in establishing several Epstein-Barr virus-immortalized B-cell lines
      from PBMCs of HCV-positive patients. Two of these cell lines are positive for HCV
      RNA as detected by reverse transcriptase PCR and for the nonstructural protein
      NS3 by immunofluorescence staining. These observations unequivocally establish
      that HCV infects B cells in vivo and in vitro. HCV-infected cell lines show
      significantly enhanced apoptosis. These B-cell lines provide a reproducible cell
      culture system for studying the complete replication cycle and biology of HCV
      infections.

PMID- 12525649
TI  - Determinant for endoplasmic reticulum retention in the luminal domain of the
      human cytomegalovirus US3 glycoprotein.
AB  - US3 of human cytomegalovirus is an endoplasmic reticulum resident transmembrane
      glycoprotein that binds to major histocompatibility complex class I molecules and
      prevents their departure. The endoplasmic reticulum retention signal of the US3
      protein is contained in the luminal domain of the protein. To define the
      endoplasmic reticulum retention sequence in more detail, we have generated a
      series of deletion and point mutants of the US3 protein. By analyzing the rate of
      intracellular transport and immunolocalization of the mutants, we have identified
      Ser58, Glu63, and Lys64 as crucial for retention, suggesting that the retention
      signal of the US3 protein has a complex spatial arrangement and does not comprise
      a contiguous sequence of amino acids. We also show that a modified US3 protein
      with a mutation in any of these amino acids maintains its ability to bind class I
      molecules; however, such mutated proteins are no longer retained in the
      endoplasmic reticulum and are not able to block the cell surface expression of
      class I molecules. These findings indicate that the properties that allow the US3
      glycoprotein to be localized in the endoplasmic reticulum and bind major
      histocompatibility complex class I molecules are located in different parts of
      the molecule and that the ability of US3 to block antigen presentation is due
      solely to its ability to retain class I molecules in the endoplasmic reticulum.

PMID- 12525650
TI  - Nuclear localization of the duck hepatitis B virus capsid protein: detection and
      functional implications of distinct subnuclear bodies in a compartment associated
      with RNA synthesis and maturation.
AB  - We have reinvestigated the subcellular distribution of the duck hepatitis B virus
      (DHBV) core protein in infected duck hepatocytes and in transfected cells. By
      using indirect immunofluorescence, the protein was found to be localized not only
      in the cytoplasm, as described previously, but also within the cell nucleus,
      being concentrated in distinct, brightly staining nuclear core bodies (NCBs). In
      colocalization studies using confocal microscopy, the NCBs were found exclusively
      in the periphery of nuclear subdomains characterized as splicing factor
      compartments and distal to other subnuclear domains. Also relevant for their
      functional significance is that the NCBs formed during the establishment of virus
      infection, i.e., at very low overall concentrations of newly synthesized core
      protein, and persisted throughout all stages of infection. Moreover, a subset of
      NCBs colocalized with foci of pregenomic DHBV RNA present at concentrations
      detectable by fluorescence in situ hybridization. Taken together, these findings
      indicate that a minor fraction of the DHBV core protein molecules escapes the
      major cytoplasmic assembly pathway to accumulate in specific subnuclear domains,
      and they furthermore suggest that these NCBs serve a role in the synthesis and/or
      maturation of the DHBV RNA pregenome.

PMID- 12525651
TI  - Effect of humoral immune responses on controlling viremia during primary
      infection of rhesus monkeys with simian immunodeficiency virus.
AB  - Cellular immune responses mediated by CD8+ lymphocytes exert efficient control of
      virus replication during primary simian immunodeficiency virus (SIV) infection.
      However, the role that antibodies may play in the early control of virus
      replication remains unclear. To evaluate how antibody responses may affect virus
      replication during primary SIVmac infection, we depleted rhesus monkeys of B
      cells with anti-CD20 antibody. In normal rhesus monkeys immunized with tetanus
      toxoid, anti-CD20 treatment and resulting depletion of B cells inhibited the
      generation of antitetanus antibodies, while tetanus-specific T-cell responses
      were preserved. During the first 4 weeks after inoculation with SIVmac251,
      development of SIV-specific neutralizing antibody was delayed, and titers were
      significantly lower in B-cell-depleted monkeys than control-antibody-treated
      monkeys. Despite the lower neutralizing antibody titers, the levels of plasma SIV
      RNA and the linear slope of the decline seen in B-cell-depleted monkeys did not
      differ from that observed in monkeys treated with control antibody. However,
      beginning at day 28 after SIV infection, the B-cell-depleted monkeys showed a
      significant inverse correlation between neutralizing antibody titers and plasma
      virus level. These results suggest that the rapid decline of peak viremia that
      typically occurs during the first 3 weeks of infection was not significantly
      affected by SIV-specific antibodies. However, the inverse correlation between
      neutralizing antibodies and plasma virus level during the postacute phases of
      infection suggests that humoral immune responses may contribute to the control of
      SIV replication.

PMID- 12525652
TI  - Virus replication in engineered human cells that do not respond to interferons.
AB  - The V protein of the paramyxovirus simian virus 5 blocks interferon (IFN)
      signaling by targeting STAT1 for proteasome-mediated degradation. Here we report
      on the isolation of human cell lines that express the V protein and can no longer
      respond to IFN. A variety of viruses, particularly slow-growing wild-type viruses
      and vaccine candidate viruses (which are attenuated due to mutations that affect
      virus replication, virus spread, or ability to circumvent the IFN response), form
      bigger plaques and grow to titers that are increased as much as 10- to 4,000-fold
      in these IFN-nonresponsive cells. We discuss the practical applications of using
      such cells in vaccine development and manufacture, virus diagnostics and
      isolation of newly emerging viruses, and studies on host cell tropism and
      pathogenesis.

PMID- 12525653
TI  - Cytomegalovirus-mediated upregulation of chemokine expression correlates with the
      acceleration of chronic rejection in rat heart transplants.
AB  - Cytomegalovirus (CMV) infections have been shown to dramatically affect solid
      organ transplant graft survival in both human and animal models. Recently, it was
      demonstrated that rat CMV (RCMV) infection accelerates the development of
      transplant vascular sclerosis (TVS) in both rat heart and small bowel graft
      transplants. However, the mechanisms involved in this process are still unclear.
      In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat
      heart transplant model. Acute RCMV infection enhances the development of TVS in
      rat heart allografts, and this process is initiated between 21 and 24 days
      posttransplantation. The virus is consistently detected in the heart grafts from
      day 7 until day 35 posttransplantation but is rarely found at the time of graft
      rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had
      upregulation of chemokine expression compared to uninfected controls, and the
      timing of this increased expression paralleled that of RCMV-accelerated
      neointimal formation. In addition, graft vessels from RCMV-infected grafts
      demonstrate the increased infiltration of T cells and macrophages during periods
      of highest chemokine expression. These results suggest that CMV-induced
      acceleration of TVS involves the increased graft vascular infiltration of
      inflammatory cells through enhanced chemokine expression.

PMID- 12525654
TI  - The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display
      transforming properties.
AB  - Several studies have suggested the involvement of cutaneous human
      papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we
      have characterized the in vitro properties of E7 proteins of three cutaneous HPV
      types, 10, 20, and 38, which are frequently detected in skin specimens. We show
      that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of
      G(1)/S transition control, a key event in carcinogenesis. In contrast, HPV10 and
      HPV20 E7 proteins do not display these in vitro transforming activities. We also
      show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the
      cell cycle and senescence programs in primary cells, inducing active and long
      lasting proliferation of primary human keratinocytes, the natural host cells. Our
      study shows that E6 and E7 of this cutaneous HPV type have transforming activity
      in primary human cells, suggesting a role for HPV38 infection in skin
      carcinogenesis. In further support of such a role, we detected HPV38 DNA in
      approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin
      specimens (P < 0.001).

PMID- 12525655
TI  - The promyelocytic leukemia protein does not mediate foamy virus latency in vitro.
AB  - Spumaviruses, commonly called foamy viruses, are complex retroviruses that
      establish life-long persistent infections in the absence of accompanying
      pathology. Depending upon cell type, infection of cells in tissue culture cells
      can result in either lytic replication, persistence, or latency. The cellular
      factors that mediate foamy virus (FV) latency are poorly understood. In this
      study we show that the only known inhibitor of FV replication, the promyelocytic
      leukemia protein (PML), which binds the FV transactivator (Tas), does not play an
      important role in FV latency in vitro. We found no significant differences in PML
      levels in cells that supported lytic replication compared to those that were
      latently infected. Furthermore, endogenous PML levels did not change following
      exposure to phorbol myristate acetate (PMA), which induces FV replication. We
      demonstrated that FV replication proceeded in the presence of substantial levels
      of PML, both in fully permissive cells and during reactivation of latent FV.
      Endogenous PML did not efficiently colocalize with Tas, even after upregulation
      by alpha interferon (IFN-alpha) treatment. IFN-alpha did, however, partially
      suppress the reactivation of latent FV by PMA. Finally, depletion of endogenous
      PML by small interfering RNA did not promote activation of FV in cells that
      responded to PMA treatment. Taken together, these data indicate that endogenous
      PML does not play an important role in mediating FV latency.

PMID- 12525657
TI  - In vivo induction of apoptosis correlating with reduced infectivity during
      baculovirus infection.
AB  - Spodoptera frugiperda caterpillars were infected with a mutant of Autographa
      californica M nucleopolyhedrovirus lacking the antiapoptotic p35 gene. Viral
      infectivity, replication, and spread were substantially reduced compared to that
      of a control revertant virus. Terminal deoxynucleotidyltransferase-mediated dUTP
      biotin nick end labeling confirmed that apoptosis occurred in mutant-infected
      caterpillars, thus directly correlating reduced infectivity and in vivo induction
      of apoptosis.

PMID- 12525656
TI  - Noninvasive detection of new simian immunodeficiency virus lineages in captive
      sooty mangabeys: ability to amplify virion RNA from fecal samples correlates with
      viral load in plasma.
AB  - The sooty mangabey (SM) (Cercocebus atys) is the natural host of a simian
      immunodeficiency virus, termed SIVsm, which gave rise to human immunodeficiency
      virus type 2. Data on the geographic distribution, prevalence, and genetic
      diversity of SIVsm in the wild remains limited. To address this issue,
      noninvasive strategies based on screening SM fecal and urine specimens for SIVsm
      specific antibodies and virion RNA (vRNA) were developed, and the results were
      correlated with viral loads in plasma. Twenty-three SIVsm-infected and 27
      uninfected SMs were evaluated. Time-matched urine, fecal and plasma samples were
      collected over a 2-month period from 16 captive naturally infected SMs. The
      remaining 7 infected and 27 uninfected SMs were sampled once. Each specimen was
      subjected to enhanced chemiluminescence-Western blot analysis and nested reverse
      transcriptase (RT) PCR. The results showed that urine was highly sensitive (96%)
      and specific (100%) for detection of SIVsm antibodies, while fecal detection was
      much less sensitive (16%). Conversely, vRNA detection was more sensitive in feces
      (50%) than in urine (2%) samples. Fecal-vRNA detection correlated with viral
      loads in plasma (P < 0.002). SMs with detectable fecal vRNA had a mean viral load
      in plasma of 458,006 copies/ml, while those with undetectable fecal vRNA had a
      mean viral load in plasma of 29,428 copies/ml. Moreover, for every log increase
      in the viral load in plasma, the odds of detecting virus in fecal samples
      increased 87-fold. Genetic diversity of SIVsm in the SM colony was characterized
      by sequencing partial gag (846 bp) and gp43 (439 bp) fragments. Surprisingly,
      four new SIVsm lineages were identified, two of which were initially detected by
      fecal RT-PCR. This study documents the suitability of noninvasive methods for the
      detection and molecular characterization of new SIV variants. These assays will
      be useful for studying the phylogeny and epidemiology of SIVsm infections in the
      wild, and they hold promise as tools for investigating natural SIV infections in
      endangered nonhuman primates.

PMID- 12525658
TI  - Amplification of a complete simian immunodeficiency virus genome from fecal RNA
      of a wild chimpanzee.
AB  - Current knowledge of the genetic diversity of simian immunodeficiency virus
      (SIVcpz) infection of wild chimpanzees (Pan troglodytes) is incomplete since few
      isolates, mostly from captive apes from Cameroon and Gabon, have been
      characterized; yet this information is critical for understanding the origins of
      human immunodeficiency virus type 1 (HIV-1) and the circumstances leading to the
      HIV-1 pandemic. Here, we report the first full-length SIVcpz sequence (TAN1) from
      a wild chimpanzee (Pan troglodytes schweinfurthii) from Gombe National Park
      (Tanzania), which was obtained noninvasively by amplification of virion RNA from
      fecal samples collected under field conditions. Using reverse transcription-PCR
      and a combination of generic and strain-specific primers, we amplified 13
      subgenomic fragments which together spanned the entire TAN1 genome (9,326 bp).
      Distance and phylogenetic tree analyses identified TAN1 unambiguously as a member
      of the HIV-1/SIVcpz group of viruses but also revealed an extraordinary degree of
      divergence from all previously characterized SIVcpz and HIV-1 strains. In Gag,
      Pol, and Env proteins, TAN1 differed from west-central African SIVcpz and HIV-1
      strains on average by 36, 30, and 51% of amino acid sequences, respectively,
      approaching distance values typically found for SIVs from different primate
      species. The closest relative was SIVcpzANT, also from a P. t. schweinfurthii
      ape, which differed by 30, 25, and 44%, respectively, in these same protein
      sequences but clustered with TAN1 in all major coding regions in a statistically
      highly significant manner. These data indicate that east African chimpanzees,
      like those from west-central Africa, are naturally infected by SIVcpz but that
      their viruses comprise a second, divergent SIVcpz lineage which appears to have
      evolved in relative isolation for an extended period of time. Our data also
      demonstrate that noninvasive molecular epidemiological studies of SIVcpz in wild
      chimpanzees are feasible and that such an approach may prove essential for
      unraveling the evolutionary history of SIVcpz/HIV-1 as well as that of other
      pathogens naturally infecting wild primate populations.

PMID- 12525659
TI  - The foot-and-mouth disease virus cis-acting replication element (cre) can be
      complemented in trans within infected cells.
AB  - A temperature-sensitive (ts) mutation was identified within the 5'-untranslated
      region of foot-and-mouth disease virus (FMDV) RNA. The mutation destabilizes a
      stem-loop structure recently identified as a cis-acting replication element
      (cre). Genetic analyses indicated that the ts defect in virus replication could
      be complemented. Thus, the FMDV cre can function in trans. It is suggested that
      the cre be renamed a 3B-uridylylation site (bus).

PMID- 12525660
TI  - CD154 blockade results in transient reduction in Theiler's murine
      encephalomyelitis virus-induced demyelinating disease.
AB  - Transient CD154 blockade at the onset of Theiler's murine encephalomyelitis virus
      induced demyelinating disease ameliorated disease progression for 80 days,
      reduced immune cell infiltration, and transiently increased viral loads in the
      central nervous system. Peripheral antiviral and autoimmune T-cell responses were
      normal, and disease severity returned to control levels by day 120.

PMID- 12525661
TI  - Frequency and phenotype of circulating Valpha24/Vbeta11 double-positive natural
      killer T cells during hepatitis C virus infection.
AB  - Natural killer T (NKT) cells are thought to be involved in innate responses
      against infection. We investigated one specific type of NKT cell,
      Valpha24/Vbeta11 double positive, in hepatitis C virus (HCV) infection. Lower
      frequencies of this population were detected in the blood of HCV PCR-positive
      patients than in controls. Unlike Valpha24/Vbeta11 NKT cells found in blood,
      those in the liver appeared to be recently activated.

PMID- 12525662
TI  - Recognition of a novel stage of betaherpesvirus latency in human herpesvirus 6.
AB  - Latency-associated transcripts of human herpesvirus 6 (H6LTs) (K. Kondo et al. J.
      Virol. 76:4145-4151, 2002) were maximally expressed at a fairly stable
      intermediate stage between latency and reactivation both in vivo and in vitro.
      H6LTs functioned as sources of immediate-early protein 1 at this stage, which up
      regulated the viral reactivation.

PMID- 12525663
TI  - Fine mapping of a cis-acting sequence element in yellow fever virus RNA that is
      required for RNA replication and cyclization.
AB  - We present fine mapping of a cis-acting nucleotide sequence found in the 5'
      region of yellow fever virus genomic RNA that is required for RNA replication.
      There is evidence that this sequence interacts with a complementary sequence in
      the 3' region of the genome to cyclize the RNA. Replicons were constructed that
      had various deletions in the 5' region encoding the capsid protein and were
      tested for their ability to replicate. We found that a sequence of 18 nucleotides
      (residues 146 to 163 of the yellow fever virus genome, which encode amino acids 9
      to 14 of the capsid protein) is essential for replication of the yellow fever
      virus replicon and that a slightly longer sequence of 21 nucleotides (residues
      146 to 166, encoding amino acids 9 to 15) is required for full replication. This
      region is larger than the core sequence of 8 nucleotides conserved among all
      mosquito-borne flaviviruses and contains instead the entire sequence previously
      proposed to be involved in cyclization of yellow fever virus RNA.

PMID- 12525664
TI  - In a subset of subjects on highly active antiretroviral therapy, human
      immunodeficiency virus type 1 RNA in plasma decays from 50 to <5 copies per
      milliliter, with a half-life of 6 months.
AB  - Three of five virally suppressed human immunodeficiency virus type I (HIV-1)
      infected patients treated with highly active antiretroviral therapy and followed
      intensively with a supersensitive reverse transcriptase PCR assay with a lower
      limit of quantitation of 5 copies/ml showed statistically significant viral load
      decays below 50 copies/ml, with half-lives of 5 to 8 months and a mean of 6
      months. This range of half-lives is consistent with the estimated half-life of
      the latent HIV-1 reservoir in the peripheral blood. Those patients without decay
      of viral load in plasma may have significant cryptic HIV-1 residual replication.

PMID- 12525665
TI  - Protein phosphatase 2A enhances activation of human immunodeficiency virus type 1
      by phorbol myristate acetate.
AB  - The viral replication rate in patients infected with human immunodeficiency virus
      type 1 (HIV-1) is controlled in part by regulation of the transcription of viral
      genes. The rate of transcription is determined by a complex interplay between
      cellular and viral proteins and the promoter elements found in the long terminal
      repeats. Protein phosphatase 2A (PP2A) is a phosphoprotein that plays important
      roles in the regulation of signal transduction and cell growth. In this report,
      we demonstrate that overexpression of the catalytic subunit of protein
      phosphatase 2A (PP2Ac) increases the basal activity of the HIV-1 promoter and,
      especially, enhances the promoter's response to the protein kinase C (PKC)
      activator 12-O-tetradecanoyl phorbol-13-acetate (PMA). Additionally, ectopic
      PP2Ac enhances activation of HIV-1 provirus by PMA. Okadaic acid, a potent
      inhibitor of PP2A, markedly reduces both HIV-1 enhancer and proviral activation.
      Fostriecin, a PP2A inhibitor which has been used as an antineoplastic agent in
      clinical trials, is also able to inhibit PMA-stimulated HIV-1 proviral
      activation. These observations demonstrate a role for the important cellular
      phosphatase PP2A in HIV-1 transcription and replication and also suggest that PKC
      can potentiate the activity of PP2A. PP2A is a potential target for therapeutic
      intervention in patients infected with HIV-1.

PMID- 12525666
TI  - High-frequency phenotypic reversion and pathogenicity of an acyclovir-resistant
      herpes simplex virus mutant.
AB  - A double-guanine-insertion mutation within a run of guanines in the herpes
      simplex virus gene encoding thymidine kinase (TK) was previously found in an
      acyclovir-resistant clinical isolate. This mutation was engineered into strain
      KOS, and stocks were generated from single plaques. Plaque autoradiography
      revealed that most plaques in such stocks exhibited low levels of TK activity,
      while approximately 3% of plaques exhibited high levels of TK activity,
      indicating a remarkably high frequency of phenotypic reversion. This virus was
      able to reactivate from latency in mouse ganglia; a fraction of the reactivating
      virus expressed a high level of TK activity due to an additional G insertion,
      suggesting that the observed genetic instability contributed to pathogenicity.

PMID- 12525667
TI  - Duck hepatitis B virus virion secretion requires a double-stranded DNA genome.
AB  - Hepatitis B virus assembly begins with the packaging of an RNA pregenome into
      intracellular nucleocapsids, with subsequent reverse transcription within these
      nucleocapsids converting the RNA into a characteristic, partially double-stranded
      DNA, which, alone, is found in enveloped extracellular virions as the viral
      genome. Using a synchronized replication system for the duck hepatitis B virus,
      together with a stringent two-step assay for virion secretion, we demonstrate
      that this selective genome secretion results from an intrinsic secretion
      competence gained only by the nucleocapsids at the late stage of reverse
      transcription.

PMID- 12525668
TI  - In vitro RNA replication directed by replicase complexes isolated from the
      subgenomic replicon cells of hepatitis C virus.
AB  - Replication of hepatitis C virus (HCV) RNA in virus-infected cells is believed to
      be catalyzed by viral replicase complexes (RCs), which may consist of various
      virally encoded nonstructural proteins and host factors. In this study, we
      characterized the RC activity of a crude membrane fraction isolated from HCV
      subgenomic replicon cells. The RC preparation was able to use endogenous replicon
      RNA as a template to synthesize both single-stranded (ss) and double-stranded
      (ds) RNA products. Divalent cations (Mg2+ and Mn2+) showed different effects on
      RNA synthesis. Mg2+ ions stimulated the synthesis of ss RNA but had little effect
      on the synthesis of ds RNA. In contrast, Mn2+ ions enhanced primarily the
      synthesis of ds RNA. Interestingly, ss RNA could be synthesized under certain
      conditions in the absence of ds RNA, and vice versa, suggesting that the ss and
      ds RNA were derived either from different forms of replicative intermediates or
      from different RCs. Pulse-chase analysis showed that radioactivity incorporated
      into the ss RNA was chased into the ds RNA and other larger RNA species. This
      observation indicated that the newly synthesized ss RNA could serve as a template
      for a further round of RNA synthesis. Finally, 3' deoxyribonucleoside
      triphosphates were able to inhibit RNA synthesis in this cell-free system,
      presumably through chain termination, with 3' dGTP having the highest potency.
      Establishment of the replicase assay will facilitate the identification and
      evaluation of potential inhibitors that would act against the entire RC of HCV.

PMID- 12525669
TI  - Update in palliative medicine and end-of-life care.
AB  - Palliative medicine includes clinical palliative care, education, and research
      that focus on the quality of life of patients with advanced disease and their
      families. The domain of palliative medicine is the relief of suffering: physical,
      psychological, social, and spiritual. Palliative medicine and care for patients
      at the end of life and their families include the following key components:
      compassionate communication; exploration of patient and family values and goals
      of care; expert attention to relief of suffering; management of pain, depression,
      delirium, and other symptoms; awareness of the manifestations of grief; and
      sensitivity to the concerns of bereaved survivors.

PMID- 12525670
TI  - Calorie restriction, aging, and cancer prevention: mechanisms of action and
      applicability to humans.
AB  - Calorie restriction (CR) is the most effective and reproducible intervention for
      increasing lifespan in a variety of animal species, including mammals. CR is also
      the most potent, broadly acting cancer-prevention regimen in experimental
      carcinogenesis models. Translation of the knowledge gained from CR research to
      human chronic disease prevention and the promotion of healthy aging is critical,
      especially because obesity, which is an important risk factor for several chronic
      diseases, including many cancers, is alarmingly increasing in the Western world.
      This review synthesizes the key biological mechanisms underlying many of the
      beneficial effects of CR, with a particular focus on the insulin-like growth
      factor-1 pathway. We also describe some of the opportunities now available for
      investigations, including gene expression profiling studies, the development of
      pharmacological mimetics of CR, and the integration of CR regimens with targeted,
      mechanism-based interventions. These approaches will facilitate the translation
      of CR research into strategies for effective human chronic disease prevention.

PMID- 12525671
TI  - Erectile dysfunction.
AB  - Erectile dysfunction (ED) is a highly prevalent and often undertreated condition.
      It may be a symptom of underlying, chronic illness and can have a negative impact
      on quality of life, psychosocial health, and relationships. The aging of the
      population, as well as the introduction of new treatment options, such as
      sildenafil, has led to increased public awareness of this disorder. New oral
      therapeutic agents are on the horizon. This article provides an overview of the
      physiology of erection, the pathophysiology of ED, and modern patient evaluation.
      Management options, including traditional therapeutic approaches as well as the
      new generation of oral agents, are also presented.

PMID- 12525672
TI  - The hypereosinophilic syndrome revisited.
AB  - Clinical and biological features of patients with the idiopathic
      hypereosinophilic syndrome (HES) are heterogeneous. Recent evidence suggests at
      least two distinct underlying hematological disorders involving myeloid and
      lymphoid cells, respectively. We therefore suggest that the term idiopathic
      should be abandoned in the classification of HES. This review defines the
      "myeloproliferative" and "lymphocytic" variants of the HES and addresses the
      management of each variant, focusing on diagnosis and treatment of the newly
      identified lymphocytic variant.

PMID- 12525673
TI  - Studying cancer families to identify kidney cancer genes.
AB  - We studied families with multiple members affected with renal cancer to delineate
      clinically distinct forms of inherited renal cancer, and to identify and
      characterize the genes responsible for these disorders. Today, cancer geneticists
      recognize seven clinically distinct, inherited forms of epithelial renal cancer;
      genes responsible for five inherited predispositions have been found. Positional
      cloning efforts for one kidney cancer gene are nearing completion. These
      discoveries will provide diagnostic tests for these diseases, a foundation for
      studies of the relationship between genotype and phenotype, and a basis for
      studies of the pathophysiology of the diverse types of epithelial renal cancer.

PMID- 12525674
TI  - The automated external defibrillator: critical link in the chain of survival.
AB  - Sudden death due to ventricular fibrillation (VF) is the leading cause of death
      in the United States. Early defibrillation is the most important determinant of
      survival and is the key element in cardiopulmonary resuscitation. Obstacles to
      rapid defibrillation by trained emergency personnel persist, but the development
      of the automated external defibrillator (AED) promises to realize the goal of
      widespread early defibrillation and translate to an improved chance for survival
      for the cardiac arrest victim. Technological advancements have made the AED safe,
      easy to use, accurate, and effective in terminating VF. Use of the AED by trained
      nontraditional first responders (e.g., firefighters, police officers, flight
      crews) has improved survival rates in a variety of settings and forms the basis
      for public-access defibrillation.

PMID- 12525675
TI  - Genetics and arrhythmias.
AB  - The availability of chromosomal markers that span the human genome and improved
      high-throughput technology for genotyping and sequencing have led to major
      advances against genetic diseases. Genes have been identified for several
      disorders responsible for arrhythmias and sudden death. These genes all encode
      ion channels and are referred to as channelopathy genes. Congenital long QT
      syndrome is caused by mutations in genes encoding sodium or potassium channels.
      Brugada syndrome, only recently described, is due to mutations in a sodium
      channel and is an important cause of sudden death, particularly in Southeast
      Asia. Familial polymorphic ventricular tachycardia is due to a defect in the
      ryanodine receptor. A locus mapped to 10q32 is responsible for familial atrial
      fibrillation. Treatments based on knowledge of the molecular defect are being
      implemented for long QT syndrome and will probably provide paradigms for targeted
      treatment of acquired arrhythmias.

PMID- 12525676
TI  - AIDS-related malignancies.
AB  - Immunodeficiency alters the risk of cancer. Specific types of immune dysfunction
      are associated with different tumor risks, but most tumors are related to
      oncogenic viruses. In acquired immunodeficiency due to the human immunodeficiency
      virus (HIV), HIV itself rarely directly causes cancer; rather, it provides the
      immunologic background against which other viruses can escape immune control and
      induce tumors. The most common malignancies are Kaposi's sarcoma and non
      Hodgkin's lymphoma. This chapter discusses the pathophysiologic background of
      these tumors, how they have been affected by the use of anti-HIV medications, and
      their clinical management.

PMID- 12525677
TI  - Diagnosis and prevention of bovine spongiform encephalopathy and variant
      Creutzfeldt-Jakob disease.
AB  - An outbreak of bovine spongiform encephalopathy (BSE) arose in the United Kingdom
      as a result of prions entering and being recycled through the ruminant food
      chain. Humans have since developed a variant form of Creutzfeldt-Jakob disease
      (vCJD), also mostly in the United Kingdom, that occurs in younger individuals and
      causes prominent psychiatric and/or behavioral manifestations early in disease.
      Laboratory studies now provide strong evidence that the causative agent of BSE in
      cattle and vCJD in humans share a common origin. Because of a lack of information
      regarding the incubation period of vCJD and the number of people who may have
      been exposed, the future scope of this disease remains unknown. Control of the
      current and any future outbreaks in cattle requires strict measures to prevent
      contamination of the animal food chain with prions of any species. Prevention of
      human exposure mandates the avoidance of neural tissue in all human foods.

PMID- 12525678
TI  - Monoclonal antibody therapy for cancer.
AB  - Monoclonal antibody therapy has emerged as an important therapeutic modality for
      cancer. Unconjugated antibodies show significant efficacy in the treatment of
      breast cancer, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia.
      Promising new targets for unconjugated antibody therapy include cellular growth
      factor receptors, receptors or mediators of tumor-driven angiogenesis, and B cell
      surface antigens other than CD20. Immunoconjugates composed of antibodies
      conjugated to radionuclides or toxins show efficacy in non-Hodgkin's lymphoma.
      One immunoconjugate containing an antibody and a chemotherapy agent exhibits
      clinically meaningful antitumor activity in acute myeloid leukemia. Numerous
      efforts to exploit the ability of antibodies to focus the activities of toxic
      payloads at tumor sites are under way and show early promise. The ability to
      create essentially human antibody structures has reduced the likelihood of host
      protective immune responses that otherwise limit the duration of therapy.
      Antibody structures now can be readily manipulated to facilitate selective
      interaction with host immune effectors. Other structural manipulations that
      improve the selective targeting properties and rapid systemic clearance of
      immunoconjugates should lead to the design of effective new treatments,
      particularly for solid tumors.

PMID- 12525679
TI  - Functional genomic of the paraoxonase (PON1) polymorphisms: effects on pesticide
      sensitivity, cardiovascular disease, and drug metabolism.
AB  - This review focuses on the functional genomics of the human paraoxonase (PON1)
      polymorphisms. Levels and genetic variability of the PON1 position 192 isoforms
      (Gln/Arg) influence sensitivity to specific insecticides or nerve agents and risk
      for cardiovascular disease. A more recent area of investigation, the role of PON1
      in drug metabolism, is also discussed. We emphasize the importance of considering
      both PON1 isoforms and PON1 levels in disease/sensitivity association studies.

PMID- 12525680
TI  - Genetic privacy.
AB  - During the past 10 years, the number of genetic tests performed more than
      tripled, and public concern about genetic privacy emerged. The majority of states
      and the U.S. government have passed regulations protecting genetic information.
      However, research has shown that concerns about genetic privacy are
      disproportionate to known instances of information misuse. Beliefs in genetic
      determinacy explain some of the heightened concern about genetic privacy.
      Discussion of the debate over genetic testing within families illustrates the
      most recent response to genetic privacy concerns.

PMID- 12525681
TI  - Pharmacogenetics in cancer treatment.
AB  - Interindividual variability in the efficacy and toxicity of drug therapy is
      associated with polymorphisms in genes encoding drug-metabolizing enzymes,
      transporters, or drug targets. Pharmacogenetics aims to identify individuals
      predisposed to high risk of toxicity from conventional doses of cancer
      chemotherapeutic agents. We review the role of genetic polymorphisms in UGT1A1
      and TPMT, as well as mutations in DPD, in influencing drug disposition and
      toxicity. Recent studies show that pharmacogenetic determinants may also
      influence treatment outcomes. We discuss the clinical significance of
      polymorphisms in TS, MTHFR, and FCGR3A, as well as the polymorphic DNA repair
      genes XPD and XRCC1, in influencing response to chemotherapy and survival
      outcomes. Finally, the potential implications of transporter pharmacogenetics in
      influencing drug bioavailability are addressed.

PMID- 12525682
TI  - Molecular genetic risk screening.
AB  - Under the impetus of the Human Genome Project, new disease-associated genes are
      being discovered at a rapid pace. Mutations in many of these genes are present in
      a high enough proportion of the general population, or of particular ethnic
      groups, that global or targeted population screening can be contemplated. If
      performed early enough, identification of these mutations by molecular genetic
      testing can be used not merely to diagnose disease but to predict risk of future
      disease, either in the individual being tested or in his or her offspring. In
      some cases this knowledge can be the rationale for heightened surveillance and/or
      preventive or therapeutic interventions. Mass screening has already commenced for
      cystic fibrosis mutations and has been discussed for such diverse diseases as
      hereditary hemochromatosis, thrombophilias, familial cancer predispositions, and
      pharmacogenetic risk factors. However, implementation of such programs is often
      impeded by the complexity of the gene mutations, by incomplete penetrance, and by
      thorny ethical and social issues. This chapter reviews the basic criteria to be
      considered before embarking on population genetic risk screening, and examines
      multiple disease-screening examples representing a variety of modes of
      inheritance and technical challenges.

PMID- 12525683
TI  - The influence of HLA genotype on AIDS.
AB  - Genetic resistance to infectious diseases is likely to involve a complex array of
      immune-response and other genes with variants that impose subtle but significant
      consequences on gene expression or protein function. We have gained considerable
      insight into the genetic determinants of HIV-1 disease, and the HLA class I genes
      appear to be highly influential in this regard. Numerous reports have identified
      a role for HLA genotype in AIDS outcomes, implicating many HLA alleles in various
      aspects of HIV disease. Here we review the HLA associations with progression to
      AIDS that have been consistently affirmed and discuss the underlying mechanisms
      behind some of these associations based on functional studies of immune cell
      recognition.

PMID- 12525684
TI  - Rational design of low-molecular weight heparins with improved in vivo activity.
AB  - Heparin and low-molecular weight heparins (LMWHs), complex, sulfated
      polysaccharides isolated from endogenous sources, are potent modulators of
      hemostasis. Heparin and LMWHs interact with multiple components of the
      coagulation cascade to inhibit the clotting process. Pharmaceutical preparations
      of these complex polysaccharides, typically isolated from porcine intestinal
      mucosa, are heterogeneous in length and composition and, hence, highly
      polydisperse. Because of the structural heterogeneity of heparin and LMWHs,
      correlating their activity with a particular structure or structural motif has
      been a challenging task. Herein, we demonstrate a practical analytical method
      that enables the measurement of a structural correlate to in vivo anticoagulant
      function. With this understanding we have developed LMWHs with increased
      anticoagulant activity and decreased polydispersity. In addition to the
      pronounced anti-Xa and anti-IIa activity of these LMWHs, we also demonstrate that
      they possess desirable in vivo pharmacokinetic properties, the ability to cause
      the release of tissue factor pathway inhibitor (TFPI) from the endothelium,
      complete bioavailability through s.c. delivery, and the ability to inhibit both
      venous and arterial thromboses. Importantly, from a clinical safety point of
      view, unlike LMWHs presently used in the clinic, we show that these LMWHs are
      rapidly and completely neutralized by protamine. Together, the findings presented
      herein demonstrate a facile approach for the creation of designer LMWHs with
      optimal activity profiles.

PMID- 12525685
TI  - Mutations linked to dyskeratosis congenita cause changes in the structural
      equilibrium in telomerase RNA.
AB  - Autosomal dominant dyskeratosis congenita (DKC), as well as aplastic anemia, has
      been linked to mutations in the RNA component of telomerase, the
      ribonucleoprotein responsible for telomere maintenance. Here we examine the
      effect of the DKC mutations on the structure and stability of human telomerase
      RNA pseudoknot and CR7 domains by using NMR and thermal melting. The CR7 domain
      point mutation decreases stability and alters a conserved secondary structure
      thought to be involved in human telomerase RNA accumulation in vivo. We find that
      pseudoknot constructs containing the conserved elements of the pseudoknot domain
      are in equilibrium with a hairpin conformation. The solution structure of the
      wild-type hairpin reveals that it forms a continuous helix containing a novel run
      of three consecutive U.U and a U.C base pairs closed by a pentaloop. The six base
      pairs unique to the hairpin conformation are phylogenetically conserved in
      mammals, suggesting that this conformation is also functionally important. The
      DKC mutation in the pseudoknot domain results in a shift in the equilibrium
      toward the hairpin form, primarily due to destabilization of the pseudoknot. Our
      results provide insight into the effect of these mutations on telomerase
      structure and suggest that the catalytic cycle of telomerase involves a delicate
      interplay between RNA conformational states, alteration of which leads to the
      disease state.

PMID- 12525686
TI  - The solitary wave of asexual evolution.
AB  - Using a previously undescribed approach, we develop an analytic model that
      predicts whether an asexual population accumulates advantageous or deleterious
      mutations over time and the rate at which either process occurs. The model
      considers a large number of linked identical loci, or nucleotide sites; assumes
      that the selection coefficient per site is much less than the mutation rate per
      genome; and includes back and compensating mutations. Using analysis and Monte
      Carlo simulations, we demonstrate the accuracy of our results over almost the
      entire range of population sizes. Two limiting cases of our results, when either
      deleterious or advantageous mutations can be neglected, correspond to the Fisher
      Muller effect and Muller's ratchet, respectively. By comparing predictions of our
      model (no recombination) to those of simple single-locus models (strong
      recombination), we show that the accumulation of advantageous mutations is slowed
      by linkage over a broad, finite range of population size. This supports the view
      of Fisher and Muller, who argued in the 1930s that progressive evolution of
      organisms is slowed because loci at which beneficial mutations can occur are
      often linked together on the same chromosome. These results follow from our main
      finding, that distribution of sequences over the mutation number evolves as a
      traveling wave whose speed and width depend on population size and other
      parameters. The model explains a logarithmic dependence of steady-state fitness
      on the population size reported recently for an RNA virus.

PMID- 12525687
TI  - Quaternary structure of hemoglobin in solution.
AB  - Many important proteins perform their physiological functions under allosteric
      control, whereby the binding of a ligand at a specific site influences the
      binding affinity at a different site. Allosteric regulation usually involves a
      switch in protein conformation upon ligand binding. The energies of the
      corresponding structures are comparable, and, therefore, the possibility that a
      structure determined by x-ray diffraction in the crystalline state is influenced
      by its intermolecular contacts, and thus differs from the solution structure,
      cannot be excluded. Here, we demonstrate that the quaternary structure of
      tetrameric human normal adult carbonmonoxy-hemoglobin can readily be determined
      in solution at near-physiological conditions of pH, ionic strength, and
      temperature by NMR measurement of (15)N-(1)H residual dipolar couplings in weakly
      oriented samples. The structure is found to be a dynamic intermediate between two
      previously solved crystal structures, known as the R and R2 states. Exchange
      broadening at the subunit interface points to a rapid equilibrium between
      different structures that presumably include the crystallographically observed
      states.

PMID- 12525688
TI  - From a pump to a pore: how palytoxin opens the gates.

PMID- 12525689
TI  - Unraveling the secrets of Alzheimer's beta-amyloid fibrils.

PMID- 12525690
TI  - Contrasting roles of axonal (pyramidal cell) and dendritic (interneuron)
      electrical coupling in the generation of neuronal network oscillations.
AB  - Electrical coupling between pyramidal cell axons, and between interneuron
      dendrites, have both been described in the hippocampus. What are the functional
      roles of the two types of coupling? Interneuron gap junctions enhance synchrony
      of gamma oscillations (25-70 Hz) in isolated interneuron networks and also in
      networks containing both interneurons and principal cells, as shown in mice with
      a knockout of the neuronal (primarily interneuronal) connexin36. We have recently
      shown that pharmacological gap junction blockade abolishes kainate-induced gamma
      oscillations in connexin36 knockout mice; without such gap junction blockade,
      gamma oscillations do occur in the knockout mice, albeit at reduced power
      compared with wild-type mice. As interneuronal dendritic electrical coupling is
      almost absent in the knockout mice, these pharmacological data indicate a role of
      axonal electrical coupling in generating the gamma oscillations. We construct a
      network model of an experimental gamma oscillation, known to be regulated by both
      types of electrical coupling. In our model, axonal electrical coupling is
      required for the gamma oscillation to occur at all; interneuron dendritic gap
      junctions exert a modulatory effect.

PMID- 12525691
TI  - CCAAT/enhancer-binding protein beta is required for mitotic clonal expansion
      during adipogenesis.
AB  - Hormonal induction of growth-arrested 3T3-L1 preadipocytes triggers a signaling
      cascade that culminates in adipogenesis. CCAATenhancer-binding protein (CEBP)beta
      is expressed immediately but gains DNA-binding activity only after a long lag as
      the cells synchronously begin mitotic clonal expansion (MCE). After MCE, a
      process required for adipogenesis, CEBPbeta activates expression of CEBPalpha and
      peroxisome proliferator-activated receptor gamma, which then transcriptionally
      activate genes that produce the adipocyte phenotype. When mouse embryo
      fibroblasts (MEFs) are subjected to the same differentiation protocol, a subset
      of the MEFs undergoes a similar program of events. Similar to 3T3-L1
      preadipocytes, the MEFs reenter the cell cycle (as indicated by the synchronous
      expression of cyclin A) and undergo MCE as evidenced by the incorporation of
      BrdUrd into DNA and the formation of mitotic foci of cells that undergo
      adipogenesis. CEBPbeta is expressed immediately after induction but exhibits
      delayed acquisition of DNA-binding activity followed by expression of adipocyte
      markers and the accumulation of cytoplasmic triglyceride. MEFs from CEBPbeta(-/-)
      mice, however, neither undergo MCE nor differentiate into adipocytes. Forced
      expression of CEBPbeta (LAP) but not dominant-negative CEBPbeta (LIP) in
      CEBPbeta(-/-) MEFs restores MCE, expression of adipocyte markers, and the
      capacity to form mitotic foci of cells that undergo adipogenesis. These findings
      demonstrate that expression of CEBPbeta is a prerequisite for MCE in the
      adipocyte-differentiation program.

PMID- 12525692
TI  - Promoters of the murine embryonic beta-like globin genes Ey and betah1 do not
      compete for interaction with the beta-globin locus control region.
AB  - Mammalian beta-globin loci contain multiple beta-like genes that are expressed at
      different times during development. The murine beta-globin locus contains two
      genes expressed during the embryo stage, Ey and betah1, and two genes expressed
      at both the fetal and postnatal stages, beta-major and beta-minor. Studies of
      transgenic human beta-like globin loci in mice have suggested that expression of
      one gene at the locus will suppress expression of other genes at the locus. To
      test this hypothesis we produced mouse lines with deletions of either the Ey or
      betah1 promoter in the endogenous murine beta-globin locus. Promoter deletion
      eliminated expression of the mutant gene but did not affect expression of the
      remaining embryonic gene or the fetal-adult beta-globin genes on the mutant
      allele. These results demonstrate a lack of competitive effects between
      individual mouse embryonic beta-globin gene promoters and other genes in the
      locus. The implication of these findings for models of beta-globin gene
      expression are discussed.

PMID- 12525693
TI  - In vivo activation of a mutant mu-opioid receptor by antagonist: future direction
      for opiate pain treatment paradigm that lacks undesirable side effects.
AB  - Based on the in vitro ability of opioid antagonists to activate a mu-opioid
      receptor mutant, S196A, we reasoned that when expressed in the appropriate sites
      in vivo, this mutant receptor could be used to elicit the analgesic effects of
      the opioids without the accompanying side effects, such as tolerance and
      dependence. To test this hypothesis, we introduced the S196A mutation into the
      mouse mu-opioid receptor by a knock-in strategy to test the ability of the opioid
      antagonist to produce analgesic effects. In these homozygous mice, we observed
      increased intrinsic efficacy of opioid analgesics with two antinociceptive tests:
      hot water tail-withdrawal and acetic acid-induced writhing tests. Opioid
      antagonists, such as naloxone and naltrexone, elicited antinociceptive effects
      similar to that of partial agonists. Most importantly, chronic treatment of the
      homozygous mice with naltrexone did not produce the expected tolerance response,
      whereas less physical dependence was observed than with chronic morphine
      treatment. Such in vivo properties suggest the possibility of using the S196A
      mutant of the mu-opioid receptor and opioid antagonists to minimize the spectrum
      of unwarranted side effects in pain management when opiate analgesics are used.

PMID- 12525694
TI  - Competition for self ligands restrains homeostatic proliferation of naive CD4 T
      cells.
AB  - T cell antigen receptor (TCR) diversity is a critical feature of adaptive
      immunity. However, restriction of TCR diversity is a potential risk during immune
      reconstitution by homeostatic proliferation. What peripheral mechanisms are in
      place to maintain TCR diversity during recovery from lymphopenia? Here, we
      examine competition between several monoclonal CD4 T cell populations in RAG(-/-)
      and TCR Tg RAG(-/-) environments. The results suggest that specific self ligands
      constitute a critical limiting resource essential for homeostatic proliferation
      of naive CD4 T cells. In addition, T cells ignore large numbers of competitors as
      long as their TCR specificity is different and other non-MHC resources are not
      limiting. Therefore, the numbers of self ligands expressed in the periphery set
      the limits on TCR diversity.

PMID- 12525695
TI  - Expression of Pax4 in embryonic stem cells promotes differentiation of nestin
      positive progenitor and insulin-producing cells.
AB  - Mouse embryonic stem (ES) cells differentiate into cells of all three primary
      germ layers including endodermal cells that produce insulin in vitro. We show
      that constitutive expression of Pax4 (Pax4(+)), and to a lesser extent Pdx1
      (Pdx1(+)), affects the differentiation of ES cells and significantly promote the
      development of insulin-producing cells. In Pax4 overexpressing R1 ES cells, isl
      1, ngn3, insulin, islet amyloid polypeptide, and glucose transporter 2 (Glut-2)
      mRNA levels increase significantly. The number of nestin-expressing (nestin+)
      cells also increases. Constitutive Pax4 expression combined with selection of
      nestin+ cells and histotypic culture conditions give rise to spheroids containing
      insulin-positive granules typical of embryonal and adult beta cells. In response
      to glucose, Pax4(+) and wild-type ES-derived cells release insulin.
      Transplantation of these cells into streptozotocin-treated diabetic mice results
      in a normalization of blood glucose levels. We conclude that constitutive
      expression of Pax4 in combination with histotypic cultivation facilitates ES cell
      differentiation into the pancreatic lineage, which leads to the formation of
      islet-like spheroid structures that produce increased levels of insulin.

PMID- 12525697
TI  - Contribution of Fas to diabetes development.
AB  - Fas (Tnfrsf6, Apo-1, CD95) is a death receptor involved in apoptosis induced in
      many cell types. Fas have been shown to be expressed by insulin-producing beta
      cells in mice and humans. However, the importance of Fas in the development of
      autoimmune diabetes remains controversial. To further evaluate the importance of
      Fas in pathogenesis of diabetes, we generated NOD mice (nonobese diabetic mice
      developing spontaneous autoimmune diabetes) with beta cell-specific expression of
      a dominant-negative point mutation in a death domain of Fas, known as lpr(cg) or
      Fas(cg). Spontaneous diabetes was significantly delayed in NOD mice expressing
      Fas(cg), and the effect depended on the expression level of the transgene.
      However, Fas(cg)-bearing mice were still sensitive to diabetes transferred by
      splenocytes from overtly diabetic NOD mice. At the same time, Fas(cg) expression
      did neutralize the accelerating effect of transgenic Fas-ligand expressed by the
      same beta cells. Thus, both Fas-dependent and -independent mechanisms are
      involved in beta cell destruction, but interference with the Fas pathway early in
      disease development may retard or prevent diabetes progression.

PMID- 12525696
TI  - Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene
      expression and endothelial NO synthase activity at sites of disturbed shear
      stress.
AB  - Atherogenesis is enhanced in arterial segments exposed to disturbed blood flow,
      indicating the active participation of the hemodynamic environment in lesion
      formation. Turbulent shear stress selectively regulates responsive genes in the
      endothelium and increases the damage induced by free radicals. The purpose of the
      present study was to evaluate the effects of intervention with antioxidants and l
      arginine on endothelial NO synthase (eNOS) and oxidation-sensitive gene
      perturbation induced by disturbed flow in vitro and in vivo. Both human
      endothelial cells exposed to shear stress and high atherosclerosis-prone areas of
      hypercholesterolemic low-density lipoprotein receptor knockout (LDLR(-/-)) mice
      showed increased activities of redox-transcription factors (ELK-1, p-Jun, and p
      CREB) and decreased expression of eNOS. Intervention with antioxidants and l
      arginine reduced the activation of redox-transcription factors and increased eNOS
      expression in cells and in vivo. These results demonstrate that atherogenic
      effects induced by turbulent shear stress can be prevented by cotreatment with
      antioxidants and l-arginine. The therapeutic possibility to modulate shear stress
      response genes may have important implications for the prevention of
      atherosclerosis and its clinical manifestations.

PMID- 12525698
TI  - Modeling of the inhibitory interaction of phospholamban with the Ca2+ ATPase.
AB  - The inhibitory interaction of phospholamban (PLN) with the sarco(endo)plasmic
      reticulum Ca(2+) ATPase isoform 1 (SERCA1a) was modeled on the basis of several
      constraints which included (i) spontaneous formation of SS-bridges between
      mutants L321C in transmembrane helix 4 (M4) of SERCA1a and N27C in PLN and
      between V89C (M4) and V49C (PLN); (ii) definition of the face of the PLN
      transmembrane helix that interacts with SERCA; (iii) cross-linking between Lys-3
      of PLN and Lys-397 and Lys-400 of SERCA2a. The crystal structure of SERCA1a in
      the absence of Ca(2+), which binds PLN, was used as the structure into which an
      atomic model of PLN was built. PLN can fit into a transmembrane groove formed by
      the juxtaposition of M2, the upper part of M4, M6, and M9. In the SERCA1a
      structure with bound Ca(2+), this groove is closed, accounting for the ability of
      Ca(2+) to disrupt PLN-SERCA interactions. Near the cytoplasmic surface of the
      bilayer, the PLN helix is disrupted to prevent its collision with M4. The model
      can be extended into the cytoplasmic domain so that Lys-3 in PLN can be cross
      linked with Lys-397 and Lys-400 in SERCA1a with little unwinding of the N
      terminal helix of PLN.

PMID- 12525699
TI  - Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease.
AB  - Previous studies in Creutzfeldt-Jakob disease (CJD) have shown that myeloid cells
      in the periphery as well as derivative microglial cells in the brain are
      infectious. Microglia can show an activated phenotype before prion protein (PrP)
      pathology is detectable in brain, and isolated infectious microglia contain very
      little PrP. To find whether a set of inflammatory genes are significantly induced
      or suppressed with infection, we analyzed RNA from isolated microglia with
      relevant cDNA arrays, and identified approximately 30 transcripts not previously
      examined in any transmissible spongiform encephalopathy. This CJD expression
      profile contrasted with that of uninfected microglia exposed to prototypic
      inflammatory stimuli such as lipopolysaccharide and IFN-gamma, as well as PrP
      amyloid. These findings underscore inflammatory pathways evoked by the infectious
      agent in brain. Transcript profiles unique for CJD microglia and other myeloid
      cells provide opportunities for more sensitive preclinical diagnoses of
      infectious and noninfectious neurodegenerative diseases.

PMID- 12525700
TI  - Potent antitumor activity of a urokinase-activated engineered anthrax toxin.
AB  - The acquisition of cell-surface urokinase plasminogen activator activity is a
      hallmark of malignancy. We generated an engineered anthrax toxin that is
      activated by cell-surface urokinase in vivo and displays limited toxicity to
      normal tissue but broad and potent tumoricidal activity. Native anthrax toxin
      protective antigen, when administered with a chimeric anthrax toxin lethal
      factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing
      rapid and fatal organ damage. Replacing the furin activation sequence in anthrax
      toxin protective antigen with an artificial peptide sequence efficiently
      activated by urokinase greatly attenuated toxicity to mice. In addition, the
      mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as
      determined by using a panel of plasminogen, plasminogen activator, plasminogen
      activator receptor, and plasminogen activator inhibitor-deficient mice.
      Surprisingly, toxin activation critically depended on both urokinase plasminogen
      activator receptor and plasminogen in vivo, showing that both proteins are
      essential cofactors for the generation of cell-surface urokinase. The engineered
      toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted
      tumors of diverse origin and could eradicate established solid tumors. This
      tumoricidal activity depended strictly on tumor cell-surface plasminogen
      activation. The data show that a simple change of protease activation specificity
      converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

PMID- 12525701
TI  - Specificity of activation by phosphoinositides determines lipid regulation of Kir
      channels.
AB  - Phosphoinositides are critical regulators of ion channel and transporter
      activity. Defects in interactions of inwardly rectifying potassium (Kir) channels
      with phosphoinositides lead to disease. ATP-sensitive K(+) channels (K(ATP)) are
      unique among Kir channels in that they serve as metabolic sensors, inhibited by
      ATP while stimulated by long-chain (LC) acyl-CoA. Here we show that K(ATP) are
      the least specific Kir channels in their activation by phosphoinositides and we
      demonstrate that LC acyl-CoA activation of these channels depends on their low
      phosphoinositide specificity. We provide a systematic characterization of
      phosphoinositide specificity of the entire Kir channel family expressed in
      Xenopus oocytes and identify molecular determinants of such specificity. We show
      that mutations in the Kir2.1 channel decreasing phosphoinositide specificity
      allow activation by LC acyl-CoA. Our data demonstrate that differences in
      phosphoinositide specificity determine the modulation of Kir channel activity by
      distinct regulatory lipids.

PMID- 12525703
TI  - Global genome repair is required to activate KIN17, a UVC-responsive gene
      involved in DNA replication.
AB  - UV light provokes DNA lesions that interfere with replication and transcription.
      These lesions may compromise cell viability and usually are removed by nucleotide
      excision repair (NER). In humans, inactivation of NER is associated with three
      rare autosomal recessive inherited disorders: xeroderma pigmentosum (XP),
      Cockayne syndrome, and trichothiodystrophy. The NER earliest step is lesion
      recognition by a complex formed by XPC and HHR23B proteins. In a subsequent step,
      XPA protein becomes associated to the repair complex. Here we investigate whether
      XPA and XPC proteins, involved in global genome repair, may contribute to a
      signal transduction pathway regulating the response to UVC-induced lesions. We
      monitored the expression of several UVC-induced genes in cells deficient in
      either a transduction pathway or mutated on an NER gene. Expression of the KIN17
      gene is induced after UVC irradiation independently of p53 and of activating
      transcription factor 2. However, in human cells derived from XPA or XPC patients
      the UVC-induced accumulation of KIN17 RNA and protein is abolished. Our results
      indicate that the presence of functional XPA and XPC proteins is essential for
      the up-regulation of the KIN17 gene after UVC irradiation. They also show that
      the integrity of global genome repair is required to trigger KIN17 gene
      expression and probably other UVC-responsive genes.

PMID- 12525704
TI  - RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome degradation
      pathway.
AB  - Oocyte meiosis and early mitotic divisions in developing embryos rely on the
      timely production of cell cycle regulators and their clearance via proteasomal
      degradation. Ret Finger Protein-Like 4 (Rfpl4), encoding a RING finger-like
      protein with a B30.2 domain, was discovered during an in silico search for germ
      cell-specific genes. To study the expression and functions of RFPL4 protein, we
      performed immunolocalizations and used yeast two-hybrid and other protein-protein
      interaction assays. Immunohistochemistry and immunofluorescence showed that RFPL4
      accumulates in all growing oocytes and quickly disappears during early embryonic
      cleavage. We used a yeast two-hybrid model to demonstrate that RFPL4 interacts
      with the E2 ubiquitin-conjugating enzyme HR6A, proteasome subunit beta type 1,
      ubiquitin B, as well as a degradation target protein, cyclin B1.
      Coimmunoprecipitation analyses of in vitro translated proteins and extracts of
      transiently cotransfected Chinese hamster ovary (CHO)-K1 cells confirmed these
      findings. We conclude that, like many RING-finger containing proteins, RFPL4 is
      an E3 ubiquitin ligase. The specificity of its expression and these interactions
      suggest that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of
      oocyte cell cycle control during meiosis and the crucial oocyte-to-embryo
      transition to mitosis.

PMID- 12525705
TI  - The ecology of infectious disease: effects of host diversity and community
      composition on Lyme disease risk.
AB  - The extent to which the biodiversity and community composition of ecosystems
      affect their functions is an issue that grows ever more compelling as human
      impacts on ecosystems increase. We present evidence that supports a novel
      function of vertebrate biodiversity, the buffering of human risk of exposure to
      Lyme-disease-bearing ticks. We tested the Dilution Effect model, which predicts
      that high species diversity in the community of tick hosts reduces vector
      infection prevalence by diluting the effects of the most competent disease
      reservoir, the ubiquitous white-footed mouse (Peromyscus leucopus). As habitats
      are degraded by fragmentation or other anthropogenic forces, some members of the
      host community disappear. Thus, species-poor communities tend to have mice, but
      few other hosts, whereas species-rich communities have mice, plus many other
      potential hosts. We demonstrate that the most common nonmouse hosts are
      relatively poor reservoirs for the Lyme spirochete and should reduce the
      prevalence of the disease by feeding, but rarely infecting, ticks. By accounting
      for nearly every host species' contribution to the number of larval ticks fed and
      infected, we show that as new host species are added to a depauperate community,
      the nymphal infection prevalence, a key risk factor, declines. We identify
      important "dilution hosts" (e.g., squirrels), characterized by high tick burdens,
      low reservoir competence, and high population density, as well as "rescue hosts"
      (e.g., shrews), which are capable of maintaining high disease risk when mouse
      density is low. Our study suggests that the preservation of vertebrate
      biodiversity and community composition can reduce the incidence of Lyme disease.

PMID- 12525706
TI  - Hilbert series, Howe duality, and branching rules.
AB  - Let lambda be a partition, with l parts, and let F(lambda) be the irreducible
      finite dimensional representation of GL(m) associated to lambda when l < or = m.
      The Littlewood Restriction Rule describes how F(lambda) decomposes when
      restricted to the orthogonal group O(m) or to the symplectic group Sp(m2) under
      the condition that l < or = m2. In this paper, this result is extended to all
      partitions lambda. Our method combines resolutions of unitary highest weight
      modules by generalized Verma modules with reciprocity laws from the theory of
      dual pairs in classical invariant theory. Corollaries include determination of
      the Gelfand-Kirillov dimension of any unitary highest weight representation
      occurring in a dual pair setting, and the determination of their Hilbert series
      (as a graded module for p(-)). Let L be a unitary highest weight representation
      of sp(n, R), so*(2n), or u(p, q). When the highest weight of L plus rho satisfies
      a partial dominance condition called quasi-dominance, we associate to L a
      reductive Lie algebra g(L) and a graded finite dimensional representation B(L) of
      g(L). The representation B(L) will have a Hilbert series P(q) that is a
      polynomial in q with positive integer coefficients. Let delta(L) = delta be the
      Gelfand-Kirillov dimension of L and set c(L) equal to the ratio of the dimensions
      of the zeroth levels in the gradings of L and B(L). Then the Hilbert series of L
      may be expressed in the form H(L)(q)=c(L) P(q)(1-q)(delta). In the easiest
      example of the correspondence L --> B(L), the two components of the Weil
      representation of the symplectic group correspond to the two spin representations
      of an orthogonal group.

PMID- 12525707
TI  - The Red King effect: when the slowest runner wins the coevolutionary race.
AB  - Mutualisms provide benefits to those who participate in them. As a mutualism
      evolves, how will these benefits come to be allocated among the participants? We
      approach this question by using evolutionary game theory and explore the ways in
      which the coevolutionary process determines the allocation of benefits in
      mutualistic interactions. Motivated by the Red Queen theory, which states that
      coevolutionary processes favor rapid rates of evolution, we pay particular
      attention to the role of evolutionary rates in the establishment of mutualism and
      the partitioning of benefits among mutualist partners. We find that, contrary to
      the Red Queen, in mutualism evolution the slowly evolving species is likely to
      gain a disproportionate share of the benefits. Moreover, population structure
      serves to magnify the advantage to the slower species.

PMID- 12525709
TI  - Patients with clinically isolated syndromes suggestive of MS: does MRI allow
      earlier diagnosis?

PMID- 12525710
TI  - A new cause of hereditary small vessel disease: angiopathy of retina and brain.

PMID- 12525711
TI  - Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain
      injury: report of the Quality Standards Subcommittee of the American Academy of
      Neurology.
AB  - OBJECTIVE: To review the evidence regarding antiepileptic drug (AED) prophylaxis
      in patients with severe traumatic brain injury (TBI) in order to make practice
      recommendations. METHODS: The authors identified relevant studies by searching
      multiple databases and reviewing reference lists of other sources. They included
      studies that prospectively compared post-traumatic seizure rates in patients
      given AED prophylaxis vs controls. Each study was graded (class I to IV)
      according to a standard classification-of-evidence scheme and results were
      analyzed and pooled. RESULTS: Pooled class I studies demonstrated a significantly
      lower risk of early post-traumatic seizures (those occurring within 7 days after
      injury) in patients given phenytoin prophylaxis compared to controls (relative
      risk 0.37, 95% CI 0.18 to 0.74). Pooled class I and class II studies demonstrated
      no significant difference in the risk of late post-traumatic seizures (those
      occurring beyond 7 days after injury) in patients given AED prophylaxis compared
      to controls (relative risk 1.05, 95% CI 0.82 to 1.35). Serum AED levels were
      suboptimal in these studies and adverse effects were mild but frequent.
      CONCLUSIONS: For adult patients with severe TBI, prophylaxis with phenytoin is
      effective in decreasing the risk of early post-traumatic seizures. AED
      prophylaxis is probably not effective in decreasing the risk of late post
      traumatic seizures. Further studies addressing milder forms of TBI, the use of
      newer AEDs, the utility of EEG, and the applicability of these findings to
      children are recommended.

PMID- 12525712
TI  - Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie
      Tooth disease 1C.
AB  - BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathy is a heterogeneous group of
      inherited disorders of the peripheral nervous system. The authors recently mapped
      an autosomal dominant demyelinating form of CMT type 1 (CMT1C) to chromosome
      16p13.1-p12.3. OBJECTIVE: To find the gene mutations underlying CMT1C. METHODS:
      The authors used a combination of standard positional cloning and candidate gene
      approaches to identify the causal gene for CMT1C. Western blot analysis was used
      to determine relative protein levels in patient and control lymphocyte extracts.
      Northern blotting was used to characterize gene expression in 1) multiple
      tissues; 2) developing sciatic nerve; and 3) nerve-crush and nerve-transection
      experiments. RESULTS: The authors identified missense mutations (G112S, T115N,
      W116G) in the LITAFgene (lipopolysaccharide-induced tumor necrosis factor-alpha
      factor) in three CMT1C pedigrees. LITAF, which is also referred to as SIMPLE, is
      a widely expressed gene encoding a 161-amino acid protein that may play a role in
      protein degradation pathways. The mutations associated with CMT1C were found to
      cluster, defining a domain of the LITAF protein having a critical role in
      peripheral nerve function. Western blot analysis suggested that the T115N and
      W116G mutations do not alter the level of LITAF protein in peripheral blood
      lymphocytes. The LITAF transcript is expressed in sciatic nerve, but its level of
      expression is not altered during development or in response to nerve injury. This
      finding is in stark contrast to that seen for other known genes that cause CMT1.
      CONCLUSIONS: Mutations in LITAF may account for a significant proportion of CMT1
      patients with previously unknown molecular diagnosis and may define a new
      mechanism of peripheral nerve perturbation leading to demyelinating neuropathy.

PMID- 12525713
TI  - New diagnostic criteria for multiple sclerosis: application in first
      demyelinating episode.
AB  - BACKGROUND: Recently developed diagnostic criteria for MS (McDonald criteria)
      indicate that in patients with a single demyelinating episode (clinically
      isolated syndromes [CIS]), evidence for dissemination in space and time,
      essential for diagnosis, may be provided by MRI. OBJECTIVE: To assess the
      usefulness of these new criteria in patients with CIS suggestive of MS. METHODS:
      A total of 139 patients with CIS followed for a median of 3 years underwent brain
      MRI within 3 months of their first attack and again 12 months later. The number
      and location of lesions at baseline, the development of new lesions at follow-up,
      and the results of CSF examination (which, if positive, requires fewer MR
      abnormalities for diagnosis) were analyzed. The new McDonald criteria
      (incorporating MRI) were compared to the existing Poser diagnostic criteria and
      their accuracy was evaluated. RESULTS: At 12 months, 11% had clinically definite
      MS according to the Poser criteria compared to 37% with the McDonald criteria.
      Eighty percent of patients fulfilling these new criteria developed a second
      clinical episode within a mean follow-up of 49 months. The new criteria showed a
      sensitivity of 74%, specificity of 86%, and accuracy of 80% in predicting
      conversion to clinically definite MS. CONCLUSION: One year after symptom onset,
      more than three times as many patients with CIS were diagnosed with MS using new
      diagnostic criteria incorporating MRI results compared to older criteria.
      However, the proposed MRI criteria require further prospective studies to
      optimize sensitivity and specificity.

PMID- 12525714
TI  - Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS
      12).
AB  - OBJECTIVE: To develop a patient-based measure of walking ability in MS. METHODS:
      Twelve items describing the impact of MS on walking (12-Item MS Walking Scale
      [MSWS-12]) were generated from 30 patient interviews, expert opinion, and
      literature review. Preliminary psychometric evaluation (data quality, scaling
      assumptions, acceptability, reliability, validity) was undertaken in the data
      generated by 602 people from the MS Society membership database. Further
      psychometric evaluation (including comprehensive validity assessment,
      responsiveness, and relative efficiency) was conducted in two hospital-based
      samples: people with primary progressive MS (PPMS; n = 78) and people with
      relapses admitted for IV steroid treatment (n = 54). RESULTS: In all samples,
      missing data were low (< or =3.8%), item test-retest reproducibility was high (>
      or =0.78), scaling assumptions were satisfied, and reliability was high (> or
      =0.94). Correlations between the MSWS-12 and other scales were consistent with a
      priori hypotheses. The MSWS-12 (relative efficiency = 1.0) was more responsive
      than the Functional Assessment of Multiple Sclerosis mobility scale (0.72), the
      36-Item Short Form Health Survey physical functioning scale (0.33), the Expanded
      Disability Status Scale (0.03), the 25-ft Timed Walk Test (0.44), and Guy's
      Neurologic Disability Scale lower limb disability item (0.10). CONCLUSIONS: The
      MSWS-12 satisfies standard criteria as a reliable and valid patient-based measure
      of the impact of MS on walking. In these samples, the MSWS-12 was more responsive
      than other walking-based scales.

PMID- 12525715
TI  - Neutralizing antibodies during treatment of secondary progressive MS with
      interferon beta-1b.
AB  - OBJECTIVE: To investigate the relationship between neutralizing antibodies (NAB)
      and disease progression, relapses, and MR measures of MS. METHODS: Sequential
      serum samples from all 718 patients of the European Study Group in Interferon
      beta-1b in Secondary Progressive MS were analyzed to investigate relations
      between NAB and disease progression, relapses, and MR measures. RESULTS: This
      study showed no attenuating effect of NAB development on progression in
      disability. The effects of NAB on relapse rate showed substantial variation,
      depending on the statistical approach and definition of positivity, though
      analyses comparing low- and high-NAB+ periods with NAB- periods suggested a titer
      related effect. MR T2 lesion volume changes from baseline were significantly
      higher for NAB+ patients but remained lower than for placebo patients. A
      substantial proportion of NAB+ patients became NAB-. No untoward effect of NAB
      development on safety was observed. CONCLUSION: These results support the
      conclusion that even though high NAB titers appear to have impact on treatment
      efficacy with respect to relapses, treatment decisions should be based primarily
      on clinical grounds.

PMID- 12525716
TI  - Interferon beta-1a in primary progressive MS: an exploratory, randomized,
      controlled trial.
AB  - BACKGROUND: Patients with primary progressive MS have atypical clinical and MRI
      characteristics and have been excluded from most therapeutic trials. The authors
      report a randomized, controlled trial restricted to primary progressive MS.
      METHODS: Fifty subjects were randomized to weekly IM interferon beta-1a 30
      microg, 60 microg, or placebo for 2 years. The primary endpoint was time to
      sustained progression in disability. Secondary outcomes included the timed 10
      meter walk, nine-hole peg test, and on MRI, T2 and T1 brain lesion loads and
      brain and spinal cord atrophy. RESULTS: The 30- microg dose of interferon beta-1a
      was well tolerated, but the 60- microg dose caused severe flulike reactions and
      raised liver enzymes. No treatment effect was seen on the primary endpoint.
      Subjects on interferon beta-1a 30 microg had a lower rate of accumulation of T2
      lesion load than controls (p = 0.025); subjects on 60 microg had a greater rate
      of ventricular enlargement than controls (p = 0.025). CONCLUSIONS: This study has
      demonstrated that interferon beta-1a 30 microg was well tolerated, identified
      useful outcome measures, but showed no efficacy on the primary outcome measure or
      on most of the secondary outcome measures.

PMID- 12525717
TI  - IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in
      patients with SPMS.
AB  - OBJECTIVE: To 1)determine serum levels of matrix metalloproteinase-2 (MMP-2), MMP
      9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in patients with
      secondary progressive (SP) MS; 2)determine the relationship between these serum
      levels and MRI activity; and 3) evaluate the effect of interferon (IFN) therapy
      on these measures. BACKGROUND: High serum levels of MMP-9 and low levels of TIMP
      1 predict the appearance of new gadolinium-enhancing (Gd+) lesions in relapsing
      remitting (RR) MS. METHODS: Monthly Gd+ brain MRI and measures of serum MMP-2,
      MMP-9, TIMP-1, and TIMP-2 at 3-month intervals were performed for up to 3 years
      in 33 patients with SPMS participating in a phase III study of IFNbeta-1b.
      RESULTS: Patients who developed new Gd+ lesions had higher levels of MMP-9 than
      patients who did not develop Gd+ lesions (median 351 vs 226 ng/mL, p = 0.049).
      The ratio of MMP-9/TIMP-1 predicted new Gd+ lesion on the concurrent scan (OR =
      2.23, 95% CI 0.99 to 4.99, p = 0.052) and on the following scan (OR = 2.16, 95%
      CI 1.01 to 4.63, p = 0.048), whereas levels of MMP-2/TIMP-2 did not. Median
      levels of TIMP-1 were higher and MMP-9 trended lower for IFNbeta compared to
      placebo recipients (TIMP-1: 1,450 vs 1,185 ng/mL, p = 0.024; MMP-9: 225 vs 339
      ng/mL, p = 0.081). IFNbeta did not influence levels of MMP-2 and TIMP-2.
      CONCLUSION: The ratio of MMP-9/TIMP-1 may predict MRI activity in SPMS. The
      effect of IFNbeta-1b in MS, as measured by reduction in new Gd+ lesions, may be
      partly explained by altering MMP-9/TIMP-1 ratio.

PMID- 12525718
TI  - Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and
      leukoencephalopathy.
AB  - BACKGROUND: The main hereditary vascular conditions involving both retinal and
      cerebral vessels include cerebroretinal vasculopathy, HERNS (hereditary
      endotheliopathy with retinopathy, nephropathy, and stroke), and hereditary
      vascular retinopathy; all are linked to the same locus on chromosome 3p21.
      Hereditary retinal arteriolar tortuosity is a distinct, autosomal dominant
      condition characterized by retinal arteriolar tortuosity and recurrent retinal
      hemorrhages. This condition is known to affect only retinal vessels. METHODS:
      Clinical and brain MRI investigations of eight members of a three-generation
      family and extensive biological and systemic vascular investigations within one
      affected family member were conducted. RESULTS: Six of eight family members were
      clinically symptomatic; disorders included infantile hemiparesis (2), migraine
      with aura (3), and retinal hemorrhage (1). Five individuals had retinal
      arteriolar tortuosities. A diffuse leukoencephalopathy in association with
      dilated perivascular spaces was observed in six individuals. Two family members
      had silent, deep cerebral infarcts as demonstrated on MRI. Genetic linkage
      analysis strongly suggests that this disorder is not linked to the 3p21
      hereditary vascular retinopathy/cerebroretinal vasculopathy/HERNS locus.
      CONCLUSIONS: The authors describe a novel hereditary autosomal dominant condition
      affecting both retinal and cerebral vessels and characterized by infantile
      hemiparesis, migraine with aura, retinal hemorrhage, retinal arterial tortuosity,
      and leukoencephalopathy with dilatation of perivascular spaces and microbleeds on
      brain MRI. Investigation of additional families should help to map the gene and
      to better categorize the spectrum of hereditary cerebroretinal small vessel
      diseases.

PMID- 12525719
TI  - Awareness, treatment, and control of vascular risk factors in African Americans
      with stroke.
AB  - OBJECTIVE: To investigate control of risk factors in African American patients
      with previous stroke. METHODS: The baseline history, physical examination, and
      laboratory data for 1,086 subjects enrolled in the African American Antiplatelet
      Stroke Prevention Study from 1995 to 1999 were studied. The level of awareness,
      pharmacologic treatment, and control of diabetes mellitus (casual plasma glucose
      level > or =200 mg/dL), hypertension (blood pressure > or =140/90 mm Hg), and
      hypercholesterolemia (serum total cholesterol level > or =240 mg/dL) were
      determined. RESULTS: Forty percent of subjects reported a history of diabetes
      mellitus or use of diabetic medication, and 2% of the remaining subjects had a
      serum glucose level of > or =200 mg/dL. Of those subjects known to be diabetic,
      33% had a serum glucose level of > or =200 mg/dL. A history of hypertension or
      use of antihypertensive medication was reported in 87% of subjects, and 48% of
      the remaining subjects were found to have a blood pressure of > or =140/90 mm Hg
      on exam. Of those subjects known to be hypertensive by history, 73% were on
      antihypertensive medication, but only 30% of the treated subjects had a blood
      pressure under 140/90 mm Hg. A history of hypercholesterolemia or use of a lipid
      lowering agent was reported in 40% of subjects, and 24% of the remaining subjects
      had a cholesterol level of > or =240 mg/dL. Use of a lipid-lowering agent was
      reported in 43% of subjects known to be hypercholesterolemic, and 38% of the
      hypercholesterolemic subjects had a cholesterol level of > or =240 mg/dL.
      CONCLUSION: Inadequate rates of awareness and control of cardiovascular disease
      and stroke risk factors are seen in a clinical trial of African American stroke
      patients and are comparable with those of previously published reports.

PMID- 12525720
TI  - Randomized, double-blind trial of glial cell line-derived neurotrophic factor
      (GDNF) in PD.
AB  - OBJECTIVE: To assess the safety, tolerability, and biological activity of glial
      cell line-derived neurotrophic factor (GDNF) administered by an implanted
      intracerebroventricular (ICV) catheter and access port in advanced PD.
      BACKGROUND: GDNF is a peptide that promotes survival of dopamine neurons. It
      improved 6-OHDA- or MPTP-induced behavioral deficits in rodents and monkeys.
      METHODS: A multicenter, randomized, double-blind, placebo-controlled, sequential
      cohort study compared the effects of monthly ICV administration of placebo and
      25, 75, 150, 300, and 500 to 4,000 microg of GDNF in 50 subjects with PD for 8
      months. An open-label study extended exposure up to an additional 20 months and
      maximum single doses of up to 4,000 microg in 16 subjects. Laboratory testing,
      adverse events (AE), and Unified Parkinson's Disease Rating Scale (UPDRS) scoring
      were obtained at 1- to 4-week intervals throughout the studies. RESULTS: Twelve
      subjects received placebo and seven or eight subjects were assigned to each of
      the other GDNF dose groups. "On" and "off" total and motor UPDRS scores were not
      improved by GDNF at any dose. Nausea, anorexia, and vomiting were common hours to
      several days after injections of GDNF. Weight loss occurred in the majority of
      subjects receiving 75 microg or larger doses of GDNF. Paresthesias, often
      described as electric shocks (Lhermitte sign), were common in GDNF-treated
      subjects, were not dose related, and resolved on discontinuation of GDNF.
      Asymptomatic hyponatremia occurred in over half of subjects receiving 75 microg
      or larger doses of GDNF; it was symptomatic in several subjects. The open-label
      extension study had similar AE and lack of therapeutic efficacy. CONCLUSIONS:
      GDNF administered by ICV injection is biologically active as evidenced by the
      spectrum of AE encountered in this study. GDNF did not improve parkinsonism,
      possibly because GDNF did not reach the target tissues--putamen and substantia
      nigra.

PMID- 12525721
TI  - Brain parenchyma sonography discriminates Parkinson's disease and atypical
      parkinsonian syndromes.
AB  - OBJECTIVE: To study the use of brain parenchyma sonography (BPS) in
      discriminating between patients with idiopathic PD (IPD) and atypical
      parkinsonian syndromes (APS). METHODS: Twenty-five patients with APS, 9 with
      progressive supranuclear palsy (PSP) and 16 with multiple-system atrophy (MSA),
      and 25 age-matched patients with IPD were prospectively studied with BPS
      according to a standardized protocol. RESULTS: Twenty-four of the 25 (96%) IPD
      patients exhibited hyperechogenicity of the substantia nigra (SN) but only 2 of
      23 (9%) APS patients (Mann-Whitney U test, p < 0.001). In those two APS patients,
      SN hyperechogenicity was moderate only, whereas the remaining 21 APS patients had
      normal SN echogenicity. The specificity of SN hyperechogenicity in detection of
      clinically diagnosed IPD patients was 96%, and the sensitivity was 91%. If SN
      hyperechogenicity was marked, APS could be excluded because of a positive
      predictive value of 100% for IPD. Nucleus lentiformis hyperechogenicity was found
      in 17 of 22 (77%) APS patients but in only 5 of 22 (23%) IPD patients (Mann
      Whitney U test, p < 0.001). Nucleus caudatus and thalamus echogenicity and widths
      of the third ventricle and of the frontal horns of the lateral ventricles did not
      discriminate between IPD and APS. Two patients with PSP could not be assessed
      because of an insufficient bone window. CONCLUSIONS: BPS is a novel and
      noninvasive method to differentiate highly specifically between IPD and APS.
      Therefore, BPS might become a standard investigation in parkinsonian disorders.

PMID- 12525722
TI  - How do parkinsonian signs return after discontinuation of subthalamic DBS?
AB  - OBJECTIVE: To study the reappearance of the clinical signs of PD when subthalamic
      nucleus (STN) deep brain stimulation (DBS) was turned off. METHOD: The authors
      studied 35 patients treated with STN DBS 6.7 +/- 3.3 months (mean +/- SD) after
      implantation. All were clinically improved. Twenty-four had not required any
      antiparkinsonian medication for many months and 11 were in "practically defined
      off" conditions when studied. Unified Parkinson's Disease Rating Scale (UPDRS)
      motor scores were assessed at baseline and 5, 15, 30, 60, 90, 120, 150, 180, and
      240 minutes after switching off STN DBS. RESULTS: A sequential pattern of return
      of parkinsonian signs was observed, with a fast worsening of tremor within
      minutes, followed by a smoother, slower worsening of bradykinesia and rigidity
      over half an hour to an hour, and finally a slow and steady worsening of axial
      signs over 3 to 4 hours. Ninety percent of the UPDRS motor score worsening was
      reached after 2 hours. When switching STN DBS "on" again, all motor UPDRS
      subscores improved with a similar pattern, but faster than their rate of
      worsening, especially for axial signs. CONCLUSIONS: STN DBS may act by different
      mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is
      needed to estimate the clinical effect of stimulation.

PMID- 12525723
TI  - Longitudinal changes in verbal memory in older adults: distinguishing the effects
      of age from repeat testing.
AB  - OBJECTIVE: To characterize the relationship between age-related memory change and
      repeat testing using serial administrations of the California Verbal Learning
      Test (CVLT) in 385 nondemented Baltimore Longitudinal Study of Aging participants
      aged 55 and older with two or more memory assessments. METHODS: The authors
      investigated longitudinal change and the effects of age, sex, education, and
      repeat testing on new learning and recall by analyzing measures of learning and
      interference, short- and long-delay free and cued recall, and recognition hits in
      separate mixed-effects regressions. RESULTS: The authors found cross-sectional
      effects of age (p < or = 0.001) and sex (p < or = 0.05) on learning and
      interference, regardless of baseline performance. Younger adults outperformed
      older adults, and women outperformed men. Longitudinal age changes were
      documented across total learning and long-delay free and cued recall regardless
      of baseline scores (p < or = 0.05). In addition, controlling for baseline scores
      enhanced the sensitivity for detection of longitudinal age changes on Trial 5,
      short-delay cued recall and recognition hits (p < or = 0.05). The influence of
      repeated administrations changed with advancing baseline age for total learning
      and short- and long-delay recall such that younger baseline age was associated
      with improvement over time whereas older baseline age was associated with decline
      over time. CONCLUSION: Longitudinal declines in CVLT performance exist in normal
      aging and are influenced by baseline age. Furthermore, failure to account for the
      influence of repeat testing with aging may decrease sensitivity to detect
      pathologic decline.

PMID- 12525724
TI  - The impact of comorbid disease and injuries on resource use and expenditures in
      parkinsonism.
AB  - BACKGROUND: Persons with parkinsonism have high rates of both associated and
      unrelated prevalent comorbid conditions. A better understanding of patterns of
      care and expenditures may aid in designing programs to enhance functioning,
      lengthen independent living, and manage costs. METHODS: The authors linked
      national survey data of 24,831 elderly to nearly 1.9 million Medicare claims.
      Persons with parkinsonism (n = 791) were identified from survey or Medicare
      encounters for paralysis agitans. Comorbid disease risk was measured using age
      adjusted OR with 95% CI. Comorbidity cost ratios (ratio of average per person per
      year charges for parkinsonism alone vs with comorbid conditions) were developed
      to describe incremental costs of comorbidities. RESULTS: Patients with
      parkinsonism were older (78.5 +/- 7.6 vs 75.1 +/- 8.3 years, p < 0.0001) and had
      more injuries resulting in broken bones (35.6% vs 19.5%, p < 0.0001), including
      broken hips (15.9% vs 5.8%, p < 0.0001), during the 5-year study. Broken hips
      were more prevalent among men (OR 3.4, 95% CI 2.5 to 4.8) and women (OR 2.5, 95%
      CI 2.1 to 3.1) with than without parkinsonism. Among those with parkinsonism,
      comorbidity cost ratios demonstrated two- to threefold higher charges for
      dementia, broken bones, broken hip, and diabetes. CONCLUSIONS: Comorbidity
      associated with parkinsonism is an under-recognized contribution to higher
      resource use and expenditures. Further study of injuries, dementia, and diabetes
      is required to assess whether public health interventions could reduce excess
      morbidity and expenditures associated with parkinsonism.

PMID- 12525725
TI  - fMRI identifies regional specialization of neural networks for reading in young
      children.
AB  - BACKGROUND: fMRI allows mapping of neural networks underlying cognitive networks
      during development, but few studies have systematically examined children 7 and
      younger, in whom language networks may be more diffusely organized than in
      adults. OBJECTIVE: To identify neural networks during early reading consolidation
      in young children. METHODS: The authors studied 16 normal, right-handed, native
      English-speaking children with a mean age of 7.2 years (range 5.8 to 7.9) with
      fMRI reading paradigms adjusted for reading level. Data were acquired with the
      echoplanar imaging BOLD technique at 1.5 T. Group data were analyzed with
      statistical parametric mapping (SPM-99); individual data sets were analyzed with
      a region of interest approach from individual study t maps (t = 4). The number of
      activated pixels in brain regions was determined and an asymmetry index (AI) ([L
      R]/[L+R]) calculated for each region. RESULTS: In group analysis the authors
      found prominent activation in left inferior temporal occipital junction and left
      fusiform gyrus (Brodmann area [BA] 37), middle temporal gyrus (BA 21, 22), middle
      frontal gyrus (BA 44, 45), and the supplementary motor area. Activation was
      strongly lateralized in middle frontal gyrus and Wernicke areas (AI 0.54, 0.62).
      Fourteen subjects had left-sided language lateralization, one was bilateral, and
      one had poor activation. CONCLUSIONS: The neural networks that process reading
      are strongly lateralized and regionally specific by age 6 to 7 years. Neural
      networks in early readers are similar to those in adults.

PMID- 12525726
TI  - Regional brain chemical alterations in young children with autism spectrum
      disorder.
AB  - OBJECTIVE: The authors evaluated regional brain chemistry for evidence of
      increased neuronal packing density in autism. METHODS: Forty-five 3- to 4-year
      old children with autism spectrum disorder (ASD), 13 children with typical
      development (TD), and 15 children with delayed development (DD) were studied
      using dual-echo proton echoplanar spectroscopic imaging (32 x 32 matrix-1 cm(3)
      voxels) to measure brain chemical concentrations and relaxation times. Chemical
      quantification was corrected for tissue partial volume and relative measures of
      chemical relaxation (T(2r)) were calculated from the paired echoes. Measures from
      averaged and individual regions were compared using analysis of variance
      corrected for multiple comparisons. RESULTS: ASD subjects demonstrated reduced N
      acetylaspartate (NAA) (-10%), creatine (Cre) (-8%), and myo-inositol (-13%)
      concentrations compared to TD controls and prolonged NAA T(2r) relative to TD
      (7%) and DD (9%) groups. Compared to DD subjects, children with ASD also
      demonstrated prolonged T(2r) for choline (10%) and Cre (9%). Regional analyses
      demonstrated subtle patterns of chemical alterations in ASD compared to the TD
      and DD groups. CONCLUSIONS: Brain chemical abnormalities are present in ASD at 3
      to 4 years of age. However, the direction and widespread distribution of these
      abnormalities do not support hypothesis of diffuse increased neuronal packing
      density in ASD.

PMID- 12525727
TI  - The spectrum of neuropathy in diabetes and impaired glucose tolerance.
AB  - OBJECTIVE: To compare the neuropathy associated with impaired glucose tolerance
      (IGT) and diabetes mellitus (DM) determined by oral glucose tolerance testing
      (OGTT). METHODS: Patients with peripheral neuropathy of unknown cause were
      prescribed OGTT. Duration of neuropathic symptoms, neuropathic pain, neuropathy
      classification, nerve conduction test results, and intraepidermal nerve fiber
      densities (IENFD) were compared between IGT and DM groups. RESULTS: Seventy-three
      patients completed OGTT; 41 (56%) had abnormal results. Of these 41 patients, 26
      had IGT and 15 had DM. Patients with IGT had less severe neuropathy than patients
      with diabetes, as measured by sural nerve amplitudes (p = 0.056), sural nerve
      conduction velocities (p = 0.03), and distal leg IENFD (p = 0.01). Patients with
      IGT had predominantly small fiber neuropathy, compared to patients with DM (p =
      0.05), who had more involvement of large nerve fibers. CONCLUSIONS: The
      neuropathy associated with IGT is milder than the neuropathy associated with DM.
      Small nerve fibers are prominently affected and may be the earliest detectable
      sign of neuropathy in glucose dysmetabolism. OGTT is appropriate in patients with
      idiopathic neuropathy.

PMID- 12525728
TI  - Cerebral air embolism.

PMID- 12525729
TI  - Mirtazapine induces REM sleep behavior disorder (RBD) in parkinsonism.
AB  - Shortly after initiation of mirtazapine (a noradrenergic and serotonergic
      antidepressant) treatment in four patients with parkinsonism, the authors
      observed the appearance of REM sleep behavior disorder (RBD). In the two patients
      with severe motor symptoms, RBD was accompanied by hallucinations and confusion.
      These disturbances resolved with drug discontinuation, and remained resolved by
      12- to 24-month follow-up, suggesting that RBD can be triggered by a drug lacking
      anticholinergic activity.

PMID- 12525730
TI  - Preservation of branchimotor neurons of the nucleus ambiguus in multiple system
      atrophy.
AB  - Cholinergic neurons in the nucleus ambiguus (NA) were counted in autopsy tissue
      obtained from five patients with multiple system atrophy (MSA), four patients
      with PD, and five controls. The number of neurons in the dorsal NA was not
      significantly different among the three groups. Neurons in the ventrolateral
      portion of the NA were depleted in MSA. Laryngeal stridor cannot be explained
      solely by neuronal loss in the NA.

PMID- 12525731
TI  - Body mass index and incidence of dementia: the PAQUID study.
AB  - To study the relationship between body mass index (BMI) and risk of dementia, a
      cohort of 3,646 individuals aged > or =65 years living at home and without
      cognitive disorders at baseline were followed up for 8 years (the PAQUID
      [Personnes Agees Quid] Study). Subjects with a BMI < 21 had an increased risk of
      developing dementia as compared with subjects whose BMI was between 23 and 26
      (odds ratio = 1.48, 95% CI = 1.08 to 2.04). However, when individuals who
      developed dementia early during the follow-up were excluded from the analysis,
      this relationship was no longer significant. A low BMI does not in itself seem to
      be a risk factor for dementia.

PMID- 12525732
TI  - Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil.
AB  - Gene mutations within the P/Q type neuronal calcium channel in familial
      hemiplegic migraine (FHM) suggest a therapeutic role for calcium-channel
      blockade. The authors have previously reported abortive therapy of FHM with IV
      verapamil. Here the authors describe four cases of sporadic hemiplegic migraine
      (SHM) responsive to verapamil, administered either orally or IV. The findings
      indicate that verapamil is effective therapy for both SHM and FHM.

PMID- 12525733
TI  - Fatigue and depression are associated with poor quality of life in ALS.
AB  - Twenty-five ALS subjects filled out five questionnaires: the ALS Functional
      Rating Scale, Multidimensional Fatigue Inventory, multidimensional McGill Quality
      of Life, Center of Epidemiologic Study--Depression Scale, and the Epworth
      Sleepiness Scale. Fatigue, depression, and excessive somnolence are more
      pronounced in ALS subjects than in normal controls. Both fatigue and depression
      are associated with poorer quality of life in subjects with ALS, and should be
      treated aggressively.

PMID- 12525734
TI  - Myoglobinuria and COX deficiency in a patient taking cerivastatin and
      gemfibrozil.
AB  - The authors describe a patient who presented with myoglobinuria after starting
      cerivastatin-gemfibrozil therapy. Muscle histochemistry revealed ragged-red
      fibers and cytochrome c oxidase negative (COX) fibers, and biochemistry showed a
      defect of COX activity. Immunoblot analysis showed a 60% reduction of COX I and
      COX II polypeptides. Cerivastatin myotoxicity might be related to a depletion of
      essential metabolites needed to anchor COX subunit I to mitochondrial membrane.

PMID- 12525735
TI  - Longstanding ataxic demyelinating polyneuronopathy with a novel autoantibody.
AB  - The authors describe the clinical course, postmortem findings, and
      characterization of a novel autoantibody (anti-M-phase phosphoprotein-1 [anti-MPP
      1]) in a patient with a longstanding acquired demyelinating polyneuropathy and
      neuronopathy. Postmortem examination identified active sensory neuron
      degeneration, sensory axon loss, and widespread peripheral nerve demyelination. A
      possible pathophysiologic role of anti-MPP-1 is not yet identified.

PMID- 12525736
TI  - Phase I study of thalidomide for the treatment of plexiform neurofibroma in
      neurofibromatosis 1.
AB  - An open-label phase I trial of thalidomide (TL) in 20 patients with
      neurofibromatosis 1 (NF1) treated symptomatic plexiform neurofibroma (PNF). TL
      was well tolerated in doses up to 200 mg/d. Adverse reactions included transient
      somnolence in four, evanescent rash in two, and reversible mild peripheral
      neuropathy in two patients. Four patients showed less than 25% reduction in the
      tumor size. TL may have a role in the treatment of PNF and should be explored in
      a larger controlled study, possibly using higher doses of TL.

PMID- 12525737
TI  - Use of Ephedra-containing products and risk for hemorrhagic stroke.
AB  - This case-control study examined the association between Ephedra use and risk for
      hemorrhagic stroke. For use of Ephedra at any dose during the 3 days before the
      stroke, the adjusted OR was 1.00 (95% CI 0.32 to 3.11). For daily doses of < or
      =32 mg/day, the OR was 0.13 (95% CI 0.01 to 1.54), and for >32 mg/day, the OR was
      3.59 (95% CI 0.70 to 18.35). Ephedra is not associated with increased risk for
      hemorrhagic stroke, except possibly at higher doses.

PMID- 12525738
TI  - CT assessment of conjugate eye deviation in acute stroke.
AB  - Conjugate eye deviation seen on clinical examination helps to localize pathology
      in acute ischemic stroke. Eye deviation can also be assessed on a CT head scan.
      The authors found that CT eye deviation reliably lateralizes to the ischemic
      hemisphere (positive predictive value 93%) without reference to clinical
      examination. In an era of thrombolysis and rapid decision making in acute
      ischemic stroke, eye deviation on CT can help quickly direct attention to the
      affected hemisphere.

PMID- 12525739
TI  - Hyperventilation-induced limb shaking TIA in Moyamoya disease.
AB  - The authors present a case of hyperventilation-induced left upper limb shaking
      from an underlying Moyamoya disease. Video EEG monitoring and SPECT study were
      performed. Leptomeningeal collateral circulation was investigated by conventional
      angiography and by SPECT study with acetazolamide. Limb shaking in Moyamoya
      disease may result from a transient hypoperfusion of the contralateral
      frontoparietal cortex rather than basal ganglia.

PMID- 12525740
TI  - Persistence of ictal activity after functional hemispherectomy in Rasmussen
      syndrome.
AB  - A 15-year-old girl with a 3-year history of Rasmussen syndrome (RS) underwent
      left functional hemispherectomy by central disconnection. Clinical seizures then
      ceased. Five months postoperatively, ictal EEG discharges were associated with
      focal hyperperfusion on SPECT within the disconnected hypoperfused left
      hemisphere, suggesting that the basic mechanisms of RS may continue, only to
      remit later. EEG and SPECT may complement studies of these in seizure-free
      surgically treated patients in whom clinical follow-up may be unrevealing.

PMID- 12525741
TI  - Reduced myo-inositol and total choline measured with cerebral MRS in acute
      thyrotoxic Graves' disease.
AB  - Neuropsychiatric symptoms in the acute thyrotoxic phase of Graves' disease
      suggest involvement of brain processes. Short-echo-time proton MRS was used to
      measure the cerebral metabolite profile in newly diagnosed and untreated Graves'
      disease. Sixteen patients with Graves' disease and 18 age- and sex-matched
      healthy volunteers were studied. The patients had significantly reduced total
      choline and myo-inositol in the acute phase of Graves' thyrotoxicosis compared
      with the healthy volunteers.

PMID- 12525742
TI  - The empty delta sign.

PMID- 12525743
TI  - Zonisamide-induced restless legs syndrome.

PMID- 12525744
TI  - REM sleep behavior disorder and SCA-3 (Machado-Joseph disease).

PMID- 12525745
TI  - No additional benefit of HRT on response to rivastigmine in menopausal women with
      AD.

PMID- 12525746
TI  - Pure spastic paraparesis associated with a novel presenilin 1 R278K mutation.

PMID- 12525747
TI  - Dramatic response to chemotherapy in oligodendroglial gliomatosis cerebri.

PMID- 12525748
TI  - Poem: the test.

PMID- 12525749
TI  - Jules Cotard (1840-1889).

PMID- 12525750
TI  - Clinical outcome in 287 consecutive adults (15 to 45 years) with ischemic stroke.

PMID- 12525751
TI  - Subthalamic DBS replaces levodopa in Parkinson's disease: two-year follow-up.

PMID- 12525755
TI  - Radiofrequency ablation treatment for breast cancer to meet the next challenge:
      how to treat primary breast tumor without surgery.

PMID- 12525756
TI  - Feasibility of radiofrequency ablation for primary breast cancer.
AB  - As the management of breast cancer evolves towards less invasive treatment, the
      next step is the possibility of removing the primary tumor without surgery. The
      most promising of the noninvasive ablation techniques is radiofrequency ablation,
      which uses frictional heating caused when ions in the tissue attempt to follow
      changing directions of a high frequency alternating current. The radiofrequency
      probe is typically placed into the tumor under ultrasound guidance, and the
      ablation is performed with real time ultrasound monitoring. Preliminary studies
      in which RFA was followed by standard surgical resection have indicated that this
      technique is effective for the surgical ablation of small (<or=2 cm) primary
      breast tumors. A new study at The University of Texas M. D. Anderson Cancer
      Center will use RFA as the sole local treatment of breast tumors <or=1.5 cm in
      size to determine if this technique is oncologically and cosmetically appropriate
      for the local treatment of primary breast cancer. Twenty patients with small
      tumors that are clearly identifiable and measurable by ultrasound will be
      enrolled in the study. Successful ablation will be determined by core and fine
      needle biopsies, and long-term outcomes will be assessed using imaging studies
      and quality of life measurement scales for 5 years following treatment.

PMID- 12525757
TI  - Weekly schedule of docetaxel in breast cancer: evaluation of response and
      toxicity.
AB  - Several recent studies have investigated the administration of docetaxel on a
      weekly basis. Here, we review the weekly use of docetaxel in breast cancer. To
      identify articles published on this topic we performed a computer-assisted
      MEDLINE search; additional references were found in the bibliographies of these
      articles. Several phase Tstudies of weekly docetaxel have provided encouraging
      data indicating that there is generally less myelosuppression than with the three
      week schedule in patients with a variety of advanced malignancies. Dose-limiting
      toxicities are reached at 43 to 50 mg/m(2), and the recommended dose ranges from
      36 to 42 mg/m(2). Furthermore, five studies of weekly docetaxel in patients with
      metastatic breast cancer achieved 32 to 41% response rates using 25 to 40 mg/m(2)
      of docetaxel. Myelosuppression was mild, but fatigue was common and was the most
      common reason for dose reduction. In general, the planned dose intensity was
      equivalent to those used in standard three week schedules, and fatigue, asthenia,
      nail changes, excessive lacrimation (tearing), and fluid retention became more
      common with prolonged administration of docetaxel. Thus, weekly scheduling of
      docetaxel maintains efficacy and alters the toxicity profile, and the use of
      weekly docetaxel will become a promising alternative to three week dosing in the
      treatment of advanced breast cancer once randomized controlled studies confirm
      these results. However, there is still much to learn about the role of weekly
      docetaxel in adjuvant and neoadjuvant therapy.

PMID- 12525758
TI  - What is the Japanese consensus on adjuvant chemotherapy in breast cancer?
AB  - The international conference of adjuvant therapy for primary breast cancer in St.
      Gallen and the National Institute of Health Consensus Conference for Breast
      Cancer Treatment have recommended appropriate treatment for individual subgroups
      by recurrence risk. However, evidence provided by Japanese clinical trials did
      not contribute to the consensus recommendations. To compare the risk of
      recurrence in breast cancer patients between Japan and western countries, a
      database of Japanese breast cancer patients was analyzed. From 1991 to 2001,
      approximately 12100 articles listed on MEDLINE were reviewed by abstract, and
      articles were then selected and reviewed by the authors. According to the AHPC
      (Agency for Health Care Policy and Research), quality assessment and strength for
      recommendation of the evidence from clinical trials were classified. Even though
      there are likely some unknown ethnic differences, we should provide Japanese
      patients with state of the art treatment for breast cancer in accordance with
      global standard therapies, which have been evaluated by breast cancer specialists
      in western countries.

PMID- 12525759
TI  - Bone metabolic markers in bisphosphonate therapy for skeletal metastases in
      patients with breast cancer.
AB  - The use of bisphosphonates for skeletal metastasis of breast cancer is now well
      established. Although clinical judgement for treating skeletal metastasis is
      based on symptoms and imaging studies, accurate or quantitative means are few.
      Various bone metabolic markers have been developed and these were evaluated in
      patients with metastasis to bone. Bone metabolic markers, especially resorption
      markers, have been shown to be a good tool for the monitoring the response to
      therapy for skeletal metastasis. This is also true for bisphosphonate treatment
      for skeletal metastasis. Bone metabolic markers are produced by different
      mechanisms. There are some different classes of resorption markers; tartrate
      resistant acid phosphatase (TRAP) is secreted by osteoclast, N- and C-terminal
      cross-linking telopeptide of type I collagen (NTx and CTx) are the degradation
      the products of type I collagen, mainly produced by cathepsin K, and pyridinoline
      cross-linked carboxyl-terminal telopeptides of type I collagen (I CTP) is also a
      degradation product of type I collagen, by matrix metalloproteases. Even though
      bone resorption markers are a good tool to monitor response to bisphosphonate
      therapy, there remains the question of which class of bone resorption markers is
      best suited to the task.

PMID- 12525760
TI  - Clinical efficacy of bisphosphonate therapy for bone metastasis from breast
      cancer.
AB  - Bisphosphonates inhibit osteoclastic bone resorption and are being used as
      treatment for bone metastases from breast cancer. Intravenous bisphosphonate
      therapy can significantly reduce skeletal related events (SREs) when administered
      concurrently with chemotherapy or endocrine therapy. In addition, intravenous
      bisphosphonate monotherapy is also able to alleviate cancer induced bone pain,
      and to improve bone metastases in some patients. Oral bisphosphonates are not
      routinely used for the treatment of bone metastases due to their low
      bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than
      pamidronate, is now in phase II clinical studies in Japan, and may alter the role
      of oral bisphosphonates in the treatment of bone metastasis from breast cancer.
      The ASCO guidelines recommend that patients with osteolytic bone metastases be
      treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate
      and systemic therapy. In addition, it is also recommended that current standards
      of care for cancer pain, analgesics and radiotherapy, should not be replaced with
      bisphosphonate therapy.

PMID- 12525761
TI  - Prevention of bone metastases from breast cancer by adjuvant bisphosphonate
      therapy.
AB  - There is increasing evidence regarding the importance of osteoclast activation in
      the pathogenesis of bone metastases. Cancer cells produce osteoclast-activating
      factors which play an important role in the development of bone metastases.
      Bisphosphonates are drugs that inhibit bone turnover by decreasing bone
      resorption. In patients with bone metastases from breast cancer, the
      effectiveness of bisphosphonate is well established for reducing skeletal
      complications, such as bone pain, pathological fracture, bone surgery and
      hypercalcemia. Recent attention has focused on a possible preventive effect on
      bisphosphonates of bone metastases. Animal models have supported the prevention
      of bone metastasis by bishosphonate therapy, but three major adjuvant clinical
      trials of the oral bisphosphonate clodronate have yielded conflicting results.
      However, our preliminary trial of intravenous bisphosphonate with pamidronate
      showed effective inhibition of bone metastases. Use of bisphosphonates as
      adjuvant therapy is still investigational yet promising. Several more randomized
      trials are underway to further investigate adjuvant therapy with bisphosphonates.

PMID- 12525762
TI  - Significance of serum carcinoembryonic antigen and CA 15-3 in monitoring advanced
      breast cancer patients treated with systemic therapy: a large-scale retrospective
      study.
AB  - OBJECTIVE: The significance of serum carcinoembryonic antigen (CEA) and CA 15-3
      in monitoring advanced breast cancer is still controversial. To clarify this
      issue, the Tumor Marker Study Group of the Japanese Breast Cancer Society
      conducted a large-scaled retrospective study. METHODS: The findings from four
      clinical trials and seven institutes of 528 patients with advanced breast cancer
      were collected. Three-hundred forty-eight patients, in whom both serum CEA and CA
      15-3 were measured during therapy, were selected for analysis. RESULTS: The
      pretreatment positivity rate of CA 15-3 was significantly higher than that of CEA
      (p<0.0001). Time-to-progression (TTP) in CEA- and CA 15-3-positive patients was
      significantly shorter than TTP in negative patients. The changes in either marker
      level correlated well with response to therapy in marker-positive patients but
      not in negative patients. TTP in the marker-positive patients with a greater than
      20%-reduction in either marker level during therapy was significantly longer than
      that in positive patients without such a reduction (p<0.01 for CEA and CA 15-3).
      CONCLUSION: CA 15-3 is more useful for monitoring advanced breast cancer than CEA
      and a greater than 20%-reduction in marker levels suggests longer TTP in
      pretreatment marker-positive patients.

PMID- 12525763
TI  - Impact of established risk factors for breast cancer in nulligravid Japanese
      women.
AB  - BACKGROUND: The mechanism by which pregnancy impacts breast cancer risk remains
      poorly understood. There is a need for detailed quantification of risk in
      nulliparous women. We therefore have undertaken a case-referent study of breast
      cancer employing data from the Hospital-based Epidemiologic Research Program at
      Aichi Cancer Center (HERPACC), Japan, examining the impact of reproductive and
      anthropometric factors on breast cancer risk among nulligravid women compared
      with their parous counterparts. METHODS: In total, 2032 breast cancer cases were
      included, and 17848 women, confirmed as free of cancer, were recruited as a
      reference group. Odds ratios (OR) and 95% confidence intervals (95% CI) were
      determined by multiple logistic regression analysis. RESULTS: A protective effect
      of later age at menarche was observed among parous women, but it did not alter
      risk in nulligravid cases. The risk increment with a family history appeared to
      be most pronounced among premenopausal cases with no history of pregnancy
      (OR=2.68, 95% CI: 1.41-5.11). Among postmenopausal women, positive associations
      with height and current body mass index (BMI) in the nulligravid group were
      similar to those observed in the parous group. The present study indicated that
      age at menopause, family history in premenopausal women, and height and obesity
      in postmenopausal women seemed to exert more influence in nulligravid women.
      Formal tests for interaction between maternity status and these factors, however,
      did not prove statistically significant. CONCLUSION: Our findings suggest that
      established risk factors for breast cancer have an additive impact with
      nulligravid status. Thus, it is implied that obesity control for all women,
      including nulliparous individuals, is important from a practical viewpoint for
      primary breast cancer prevention.

PMID- 12525764
TI  - Estimation of individualized probabilities of developing breast cancer for
      Japanese women.
AB  - BACKGROUND: Projecting individualized probabilities of developing breast cancer
      is needed for counseling and chemoprevention for Japanese women, in whom breast
      cancer incidence has been rapidly increasing. METHODS: We calculated
      individualized probabilities of developing breast cancer within 10-20 years and
      until life expectancy for Japanese women by multiplying the relative risk for
      each risk factor combination by the cumulative risk for the reference group. The
      risk factors used were age at menarche, age at first delivery, family history of
      breast cancer, and body mass index (BMI) (in post-menopausal women). The relative
      risk by menopausal status for each risk factor combination was estimated from a
      case control study conducted at Osaka Medical Center for Cancer and
      Cardiovascular Diseases (OMCC), Japan. The cumulative risk of breast cancer for
      the reference group within 10-20 years and until life expectancy was estimated to
      divide the corresponding cumulative risk for Japanese women by the weighted
      average of the relative risk. The weight is an expected proportion of those who
      have each risk factor combination among the general population. The cumulative
      risk for Japanese women was estimated using a data file from the Osaka Cancer
      Registry (OCR). RESULTS: We obtained cumulative risks for any age women within a
      certain range according to various risk factor combinations by menopausal state.
      For example, the highest risk group had about a 5 times higher risk probability
      of developing breast cancer than the general population at initial age 40, within
      10-20 years, and until life expectancy. CONCLUSION: The cumulative risk of breast
      cancer varied according to individuals' risk factors among Japanese women. The
      availability of concrete individualized risk estimation figures will be of use to
      health care providers in encouraging Japanese women to seek counseling and to
      adopt self-control of body weight as a primary preventive measure, as well as to
      have breast cancer screening.

PMID- 12525765
TI  - Transforming growth factor B1 T29C polymorphism and breast cancer risk in
      Japanese women.
AB  - BACKGROUND: A cohort study for Caucasians aged 65 years or older demonstrated a
      marked breast cancer risk reduction for those with the CC genotype of
      transforming growth factor B1 (TGF B1) T29C polymorphism. This is a prevalent
      case-control study to examine the reported risk reduction for Japanese women.
      PATIENTS AND METHODS: A total of 232 histologically diagnosed breast cancer
      patients who visited Aichi Cancer Center Hospital between June 1999 and March
      2000 were enrolled. The controls were 172 female outpatients without cancer at
      the same hospital. DNA was extracted from peripheral blood, and TGF B1 genotype
      was determined by PCR-CTPP. RESULTS: The genotype frequency was 23.7% for TT,
      49.2% for TC, and 27.1% for CC among controls, and 28.9%, 46.1%, and 25.0%,
      respectively, among cases. Age-adjusted odds ratio (OR) relative to the TT
      genotype was 0.81 (95% confidence interval, 0.50-1.31) for the TC genotype and
      0.77 (0.45-1.34) for the CC genotype. For premenopausal women, the CC genotype
      was significantly associated with reduced risk of breast cancer in comparison
      with the TT genotype (OR=0.45, 0.20-0.98). The association was not observed for
      postmenopausal women (OR=1.40, 0.64-3.08). CONCLUSION: The present study showed
      risk reduction for Japanese premenopausal women with the CC genotype, but not for
      postmenopausal Japanese women.

PMID- 12525766
TI  - Estrogen receptor alpha mutation (A-to-G transition at nucleotide 908) is not
      found in different types of breast lesions from Japanese women.
AB  - BACKGROUND: An estrogen receptor (ER) alpha variant with an A-to-G transition at
      nucleotide 908 (A908G) has been identified in typical hyperplastic mammary
      epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at
      residue 303 within exon 4 at the border of the hinge and hormone-binding domains
      of the ER alpha, shows increased sensitivity to estrogen compared with wild-type
      ER alpha. METHODS: To investigate whether this mutation was present in breast
      lesions, we performed mutation analyses using the PCR-restriction fragment length
      polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast
      tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive
      ductal carcinoma (IDC). When we extracted DNA, the hyperplastic epithelium and
      cancer cells of DCIS were microdissected. We also performed direct sequencing
      analysis from 7 randomly-selected representative cases of hyperplasia, 9 cases of
      benign breast tumors, 11 cases of DCIS and 20 cases of IDC. RESULTS: No A908G
      mutation was found in the ER alpha gene in these breast lesions. CONCLUSION: This
      mutation might be absent or occur in so few cells as to be undetectable by PCR
      RFLP or direct sequencing.

PMID- 12525768
TI  - Phyllodes tumor arising in ectopic breast tissue of the axilla.
AB  - We examined a 31-year-old woman with a solid mass in her left axilla. Physical
      examination and ultrasonography confirmed a 2 cm well-defined mass. Fine needle
      aspiration biopsy suggested fibroadenoma of breast. Excisional biopsy revealed
      benign phyllodes tumor of the ectopic breast tissue. Phyllodes tumor in ectopic
      breast tissue is an extremely rare occurrence. Only nine cases have been
      reported, including tumors of the vulva, inguinal region and axilla. This is the
      second case in the axillary region.

PMID- 12525767
TI  - Detection of MUC1 and keratin 19 mRNAs in the bone marrow by quantitative RT-PCR
      predicts the risk of distant metastasis in breast cancer patients.
AB  - BACKGROUND: Early detection of micrometastasis in bone marrow is critical for the
      prognosis of breast cancer patients. Quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) has been used to detect cancer cells in bone
      marrow, but its utility as a prognostic factor still remains obscure. MATERIALS
      AND METHODS: Bone marrow samples were aspirated from the anterosuperior iliac
      spine of 34 patients, immediately after their surgical procedures had been
      completed. Control samples were also obtained from 10 healthy adult volunteers.
      The total RNA was extracted from the mononuclear cells, and the expression levels
      ofbeta-actin, MUC1 and keratin 19 mRNAs were studied by quantitative RT-PCR. Each
      mRNA level was scored according to the expression level. The sum of these
      expression scores was defined as the composite expression score, which was
      employed as the basis of the evaluation. RESULTS: The mean follow-up period was
      45 months. Nine patients developed distant metastases, and one developed local
      recurrence. The 4-year disease relapse rates were 75% (RR=19.38; 95% CI: 1.94
      193.20), 28% (RR=3.64; 95% CI: 0.43-31.18), and 8.3% for patients with composite
      expression scores of 5/6, 3/4 and 2, respectively. The difference among the three
      groups was statistically significant (log-rank test: p=0.0029), and multivariate
      analysis also found the composite expression score to be an independent
      prognostic factor. CONCLUSIONS: Breast cancer patients who show a high composite
      expression score in bone marrow have a significantly higher risk of recurrence.

PMID- 12525769
TI  - A case of male noninvasive intracystic papillary carcinoma forming a tumor in the
      nipple duct.
AB  - Epithelial tumors forming a mass in the male nipple are very rare. Paget's
      disease, adenoma of the nipple (AON), and breast cancer must be considered for
      differential diagnosis. This report presents a 72-year-old man with spontaneous
      serous nipple discharge and an enlarged nipple measuring 2 cm in diameter.
      Ultrasonography provided no useful information regarding the nipple lesion.
      Nipple discharge cytology was negative and without any inflammatory cells. Since
      it is extremely uncommon for Paget's disease and breast cancer to cause tumor in
      the nipple, AON was suggested. However, histopathological examination of the
      nipple resection revealed noninvasive intracystic papillary carcinoma of the
      nipple. Biopsy of the nipple is often necessary to diagnose this disease.
      Moreover, excisional biopsy of the tumor is recommended when possible, since it
      can accomplish both diagnosis and treatment in cases of AON or noninvasive
      intracystic papillary carcinoma.

PMID- 12525770
TI  - [Asymptomatic aneurysms of the infrarenal abdominal aorta: should we still be
      operating?].

PMID- 12525771
TI  - [Aspirin for primary prevention of asymptomatic atherosclerosis].

PMID- 12525772
TI  - [I. In case of arteriopathy, diabetes increases the risk of death ten-fold and of
      amputation five-fold].

PMID- 12525773
TI  - [II. Vascular lesions in diabetics].

PMID- 12525774
TI  - [III. Practical consequences of recent acquisitions in diabetes].

PMID- 12525775
TI  - [IV. Management of diabetic neuropathy].

PMID- 12525776
TI  - [V. Management of diabetic heart disease].

PMID- 12525777
TI  - [VI. Contribution of duplex Doppler].

PMID- 12525778
TI  - [VII. Microcirculatory explorations].

PMID- 12525779
TI  - [VIII. Arteriography or angio-MRI? Precautions].

PMID- 12525781
TI  - [X. Local care and medical treatment of ischemic trophic disorders in the
      diabetic patients].

PMID- 12525782
TI  - [XI. Transmetatarsal amputation: a useful procedure?].

PMID- 12525783
TI  - [XII. Role of dilatation for grade IV stenosis].

PMID- 12525784
TI  - [XIII. Distal bypasses: indications, results?].

PMID- 12525785
TI  - [XIV. Current approaches and perspectives for the treatment of type 2 diabetes].

PMID- 12525787
TI  - [XVI. Two observations of arteriopathies in diabetic patients].

PMID- 12525788
TI  - [An edema after a coronarography].

PMID- 12525790
TI  - Nutrition communication: exciting opportunities for dietitians.

PMID- 12525791
TI  - Increasing portion sizes in American diets: more calories, more obesity.

PMID- 12525792
TI  - Foods commonly eaten in the United States, 1989-1991 and 1994-1996: are portion
      sizes changing?
AB  - OBJECTIVE: To compare quantities consumed per eating occasion in 1989-1991 and
      1994-1996 was the objective of this study. DESIGN: This study was a comparison
      over time. Subjects/setting Subjects were respondents in the Continuing Survey of
      Food Intakes by Individuals (CSFII) in 1989-1991 or 1994-1996. Intake data were
      processed and analyzed to provide estimates of amounts of commonly eaten foods
      consumed per eating occasion. Statistical analyses performed Approximate t tests
      were used to compare quantities of foods consumed by 1989-1991 and 1994-1996
      survey respondents. Analyses were conducted for all persons aged 2 years and over
      and for 10 age and sex groups. Significance was set at.001. RESULTS: Significant
      differences in amounts consumed were reported for approximately one third of the
      107 foods examined. Larger amounts were reported in 1994-1996 by all persons aged
      2 years and over and selected age/sex subgroups for several foods including soft
      drinks, coffee, tea, and ready-to-eat cereal. Smaller amounts were reported for
      fewer foods: margarine, mayonnaise, chicken, macaroni and cheese, and pizza.
      APPLICATIONS/CONCLUSIONS: Amounts of foods consumed per eating occasion are
      widely used for the formation of public policy, counseling, and dietary
      assessment. Changes in amounts consumed should be monitored to evaluate the need
      for revisions in policy and diet assessment protocols.

PMID- 12525793
TI  - Modifiable behavioral factors in a biopsychosocial model predict inadequate and
      excessive gestational weight gain.
AB  - OBJECTIVE: The research addresses two questions: Are potentially modifiable
      psychosocial and behavioral factors related to gestational weight gain? Do the
      same factors relate to both excessive and insufficient weight gain? DESIGN:
      Prospective cohort study that followed women from early pregnancy until two years
      postpartum. Data were collected through mailed questionnaires and an audit of the
      medical record. Subjects/setting The sample included 622 healthy adult women who
      gave birth to live singleton infants. Subjects were recruited from all women who
      registered for prenatal care in a hospital and primary care clinic system serving
      a 10-county area of Upstate New York. Statistical analyses performed Multiple
      linear and logistic regression with adjustment for timing of measurements and
      length of gestation were performed. RESULTS: Only 38% of women gained an amount
      of weight in pregnancy that was within the range recommended by the Institute of
      Medicine. Valid and easily implemented measures of change in food intake and
      physical activity from prepregnancy and cigarette smoking during pregnancy were
      each significantly (P<.05) and independently related to gestational weight gain.
      Along with other variables in a biopsychosocial regression model, these variables
      accounted for 27% of the variance in gestational weight gain and were also
      significantly related to risk of inadequate and excessive gain.
      APPLICATIONS/CONCLUSIONS: The findings facilitate the design of more effective
      nutrition interventions to promote appropriate gestational weight gain and the
      long-term health of women and their infants.

PMID- 12525794
TI  - Implementation of HACCP and prerequisite programs in school foodservice.
AB  - OBJECTIVE: The objective of this study was to determine food safety procedures
      and practices related to the hazard analysis critical control point (HACCP)
      program and prerequisite program implementation in school foodservice. DESIGN:
      This descriptive study used a mailed questionnaire to determine procedures and
      practices related to HACCP and prerequisite programs implemented in schools.
      Demographic questions related to school foodservice directors and districts were
      included. Subjects/settings The questionnaire was mailed to a national random
      sample of 600 district school foodservice directors, all 536 district school
      foodservice directors in Iowa, and 33 directors of school districts known to have
      centralized foodservice systems. Statistical analyses Descriptive statistics were
      used to summarize data. Principal component factor analysis with varimax rotation
      identified underlying factors for HACCP procedures and practices items.
      Cronbach's alpha determined reliability for items within a factor. Multiple
      linear regression determined relationships among variables, and independent t
      tests were used to compare centralized and conventional foodservice systems.
      RESULTS: Of 1,169 questionnaires mailed, 414 school foodservice directors
      responded (35.4% response rate). HACCP programs were implemented in 22% of school
      districts. Two thirds of the directors had food safety certification. Centralized
      systems implemented more food safety procedures (21.4+/-5.6, 20.4+/-5.1, P=.04)
      and practices (26.1+/-3.5, 24.8+/-4.5, P=.002) than did conventional systems.
      Having one or more employees with primary responsibility for food safety resulted
      in a higher number of procedures and practices implemented (P=.031).
      APPLICATIONS/CONCLUSIONS: School districts need to implement prerequisite
      programs so that they are ready for HACCP implementation. There are opportunities
      for dietitians to provide consulting, training, and technical assistance to
      schools on HACCP implementation.

PMID- 12525795
TI  - Nutritional status of the older adult is associated with dentition status.
AB  - OBJECTIVE: This study was designed to examine associations between the number of
      posterior occlusal pairs of teeth and the nutritional status of older adults
      participating in the third National Health and Nutrition Examination Survey
      (NHANES III) survey. DESIGN: Impaired dentition was assessed by number of
      posterior occluding pairs of teeth (grinding teeth, n=8 pairs) and complete
      denture status. Nutritional status was measured by nutrient intake, Healthy
      Eating Index (HEI) score, serum values, and body mass index (BMI).
      Subjects/setting Data from 5,958 participants in NHANES III ages 50 years and
      over with dental examination were included in the analysis. Statistical analyses
      performed Analysis of covariance and multivariate linear regression analyses were
      performed to examine associations between number of tooth pairs and nutritional
      status indicators controlled for potential confounders. RESULTS: Compared with
      individuals with five to eight posterior occluding pairs (HEI=68.2), those with
      impaired dentition (no posterior pairs, one to four pairs remaining, or full
      dentures) had consistently lower HEI scores (HEI=64.3, 66.5, and 66.5,
      respectively), consumed fewer servings of fruits, and had lower serum values of
      beta carotene and ascorbic acid. Participants with one to four posterior pairs
      also had a higher mean BMI (28.0) than those with five or more pairs (27.2).
      Participants in one or more groups with impaired dentition had lower dietary
      intake levels of vitamin A, carotene, folic acid, and vitamin C, and scored less
      well on diet variety, cholesterol, and sodium components of the HEI.
      APPLICATIONS/CONCLUSIONS: Results show that dental health is closely associated
      with nutritional status and suggest that status of dentition should be considered
      in nutritional counseling and assessment of older adults.

PMID- 12525796
TI  - Pycnogenol does not impact the antioxidant or vitamin C status of healthy young
      adults.
AB  - OBJECTIVE: The objectives of this study were to determine if Pycnogenol (PYC), a
      water-processed extract made from the bark of Pinus maritima, interacts with
      vitamin C to increase its concentration and to increase total antioxidant
      capacity of serum and urine. DESIGN: The study design was a nonrandom
      intervention. SUBJECTS: Subjects (N=27; 15 women, 12 men) were aged 19 to 42
      years. INTERVENTION: Subjects consumed a placebo twice daily with meals for the
      first 2 weeks (baseline) and PYC (200 mg/day) for the second 2 weeks. Main
      outcome measures On days 15 and 29, subjects had a fasting blood sample collected
      and then consumed a daily dose of placebo or PYC with a 310-calorie beverage. One
      hour later a second blood sample was collected. Blood samples were analyzed for
      vitamin C and total antioxidant capacity using the ORAC (oxygen radical
      absorbance capacity) assay. Twenty-four-hour urine samples were collected on days
      14-15 and 28-29 and analyzed for total phenolics, FRAP (ferric reducing
      antioxidant potential), and ORAC. Statistical analyses Paired t tests were used
      to test the impact of PYC on the outcome variables. A univariate ANOVA was used
      to determine the influence of gender. Pearson's correlation analysis was used to
      explore the relationships between dietary factors and outcome measures. RESULTS:
      There was no apparent increase in fasting vitamin C concentration (P=.18) 2 weeks
      after supplementing the diet with PYC. Fasting ORAC values actually declined
      (P=.005). One hour after the ingestion of a daily dose of placebo or PYC, the
      total antioxidant capacity of serum increased by 15% to 19%, but the increase
      after ingesting PYC was not significantly (P=.80) more than after placebo.
      Antioxidant results from 24-hour urine samples were similar.
      APPLICATIONS/CONCLUSIONS: The present findings fail to support the vitamin C or
      antioxidant claims made for PYC. PYC does not impact the antioxidant or vitamin C
      status of healthy young adults.

PMID- 12525797
TI  - California's Professional Mentoring Program: how to develop a statewide mentoring
      program.
AB  - Trends in downsizing, restructuring, increased diversity, and individual
      responsibility for career development have sparked a renewed interest in
      mentoring. Technology is changing the way professionals practice, including
      dieticians. This is reflected in the strategic goals for the American Dietetic
      Association (ADA). In 1999, with the aid of an ADA Affiliate/Dietetic Practice
      Group (DPG) Collaborative Strategic Initiatives Grant, a Mid-Career Mentoring
      Program (MCMP) was developed in California. This program provided an opportunity
      for dietitians with advanced skills (mentors) to be matched with those desiring
      to develop new skills (mentees). A six-step process was used to develop the
      program. The six steps include: appoint a coordinator; identify prospective
      mentors; locate resources; define tasks and establish procedures; identify
      mentees; and begin the program. A final product of the grant was the development
      of the handbook The Helping Hand. This handbook can be used by other affiliates
      or practice groups that may wish to develop a mentoring program. Mentoring
      programs can assist registered dietitians and DTRs (dietetic technicians,
      registered) in developing their educational plans for the new Professional
      Development 2001 certification process.

PMID- 12525798
TI  - Use of an outcomes research collaborative training curriculum to enhance entry
      level dietitians' and established professionals' self-reported understanding of
      research.
AB  - This project pilot tests a unique outcomes research training curriculum that
      prepares entry-level dietitians (goal 1) and provides established dietetics
      professionals with the resources to successfully execute an outcomes research
      plan (goal 2). The learning objectives for each goal were met via lectures and
      assignments in two courses, one taught in the fall and one in the winter semester
      of the second (senior) year of the Coordinated Program at the University of
      Missouri. At their respective healthcare facilities, registered dietitian (RD)
      preceptors along with the students progressed through all stages of the research
      process, from proposal development to data presentation. At the completion of the
      process, a questionnaire was administered to students and preceptors to evaluate
      the curriculum. Fourteen of the 15 possible student respondents and four of the
      five possible RD preceptors returned their questionnaires. Salient findings as
      well as actions to be taken in subsequent course offerings include: (a) clarify
      expectations, (b) limit geographical distance, (c) increase in-class time, (d)
      limit project scope, (e) add more statistics training/practice, (f) introduce
      outcomes research earlier, (g) preceptors' participation was positive. This
      endeavor allowed us to acquire the information and experience required to make
      outcomes research training a more significant component of dietetics education.

PMID- 12525799
TI  - The effect of fiber-rich carbohydrates on features of Syndrome X.
AB  - There has been much debate among nutritionists and scientists regarding the
      optimal dietary approach for the treatment of the Insulin Resistance Syndrome,
      also called Syndrome X. This condition, which may affect as many as 47 million
      individuals in the United States, significantly increases risk of coronary heart
      disease and stroke. Major health organizations have historically recommended high
      carbohydrate, low-fat (HCLF) diets to reduce chronic disease risk. However, there
      is evidence that a high intake of carbohydrates may adversely affect one or more
      of the abnormalities associated with this syndrome. Studies in this area have
      often had limitations. For example, some studies showing adverse effects of an
      HCLF diet have not taken into account the dietary fiber content of the diet. This
      article describes abnormalities often associated with Syndrome X, reviews the
      beneficial effects of fiber-rich carbohydrates, discusses the effect of fiber
      rich carbohydrates on features of this syndrome, and concludes with applications
      of these findings for those involved in treating individuals with features of
      this disorder. This review indicates that an HCLF dietary pattern such as that
      used in the DASH trial, with a level of dietary fiber consistent with the
      recommendations of the American Dietetic Association (eg, 20-35g/day), containing
      from 3 to 10 g soluble fiber/day, may be beneficial for treating those with
      Syndrome X.

PMID- 12525800
TI  - National survey beverage consumption data for children and adolescents indicate
      the need to encourage a shift toward more nutritive beverages.
AB  - The American Academy of Pediatrics (AAP) recently issued recommendations for 100%
      fruit juice consumption for children and adolescents. National survey data (1994
      1996, 1998 Continuing Survey of Food Intakes by Individuals) were used to
      evaluate intake of 100% fruit juice for comparison with AAP recommendations. Mean
      daily intakes of 100% fruit juice were 0.9, 4.6, and 3.4 ounces in children aged
      <6 months, 6 months-6 years, and 7-18 years, respectively, which fall within AAP
      recommendations for these age groups. At age 5, mean intake of fruit drinks and
      ades exceeded that of 100% fruit juice (P=.009). Carbonated soft drink intake
      exceeded that of 100% fruit juice at age 5 and of milk at age 13 (P<.04). By age
      13, adolescents drank more carbonated soft drinks than 100% fruit juice, milk, or
      fruit drinks and ades. Increased consumption of nutrient-dense beverages (100%
      fruit juice, milk) and water as part of a varied diet should be encouraged.

PMID- 12525801
TI  - A curriculum based on social learning theory emphasizing fruit exposure and
      positive parent child-feeding strategies: a pilot study.
AB  - This study examined the effectiveness of a nutrition intervention program to
      enhance children's knowledge, preference, and intake of whole fruit and to
      decrease parents' use of controlling child-feeding behaviors. Subjects were fifth
      and sixth-grade students (children aged 10-12 years) from Cincinnati, Ohio. Nine
      parent-child pairs completed the study. Seventeen parent-child pairs who
      expressed interest but were unable to attend more than one session served as
      controls. Based on the Social Learning Theory, the curriculum combined child
      focused interactive lessons and skill-building activities with parent-focused
      lessons on child-feeding strategies to increase the fruit intake of children.
      Change in children's knowledge, preference, and intake of fruit and parents' use
      of controlling child-feeding strategies were measured in a pretest/posttest
      manner using validated questionnaires. There was a significant increase in
      knowledge scores and fruit intake by children in the experimental vs the control
      group. Fruit preference scores were similar between groups. Additionally, there
      was a significant decrease in use of controlling child-feeding strategies by
      parents in the intervention vs the control group.

PMID- 12525802
TI  - Elderly food stamp participants are different from eligible nonparticipants by
      level of nutrition risk but not nutrient intake.
AB  - Nutrition risk, nutrient intake, and selected socioeconomic characteristics of
      elderly food stamp recipients were compared with elderly people who were eligible
      for food stamps but did not participate in the program. Data were collected by
      survey using a convenience sample of 200 low-income elderly people living in
      subsidized housing. Although there were no significant differences in food group
      or nutrient intake between participants and nonparticipants, overall, these low
      income subjects did not meet minimum Dietary Reference Intake (DRI) standards for
      many nutrients and had caloric and food group serving intakes that were below
      recommendations. Food Stamp Program participants were at significantly higher
      nutrition risk than their nonparticipating peers as detected by the Nutrition
      Screening Initiative Checklist (P< or =.01) and other indicators of disability.
      It seems that those already at highest risk were in fact participating in the
      Food Stamp Program because those eligible but not participating had significantly
      higher incomes and were at significantly lower nutritional risk.

PMID- 12525803
TI  - Research and the dietetics profession: making a bigger impact.

PMID- 12525804
TI  - Incidence of diagnosed deep vein thrombosis in the general population: systematic
      review.
AB  - OBJECTIVE: to determine the incidence of deep vein thrombosis (DVT) in the
      general population by pooling results from all studies of adequate quality.
      DESIGN: systematic review including meta-analysis. MATERIAL AND METHODS: MEDLINE
      (1966-2001) and EMBASE (1950-2001) were searched for studies on the incidence of
      DVTand thromboembolism in the general population. Studies had to attain minimum
      inclusion and quality criteria to be accepted for the review, including adequate
      specification of the diagnosis of DVT and the age range of the population. The
      appraisal of studies for inclusion and abstraction of data were carried out
      independently by each author. Incidence rates were adjusted to standardise for
      differences between studies in categories of DVT and population age structures.
      Weighted and unweighted means of incidence per 10 000 person years were
      estimated. RESULTS: nine studies were identified which fulfilled the inclusion
      and quality criteria. Most were conducted in Sweden or U.S.A. between 1976 and
      2000. The weighted mean incidence of first DVT in the whole general population
      was 5.04 (95% CI 4.70, 5.38) per 10 000 person years. The incidence was similar
      in males and females and increased dramatically with age from about 2-3 per 10
      000 person years at age 30-49 to 20 per 10 000 person years at age 70-79. Around
      40% of cases of DVT were idiopathic. CONCLUSION: this study provides the most
      comprehensive estimate to date of the incidence of DVT in the whole general
      population-around 5 per 10 000 per annum-and is a useful background figure for
      comparison with incidence in high risk groups.

PMID- 12525805
TI  - The role of platelets in peripheral vascular disease.
AB  - Platelets play a major role in acute ischaemic syndromes and peripheral vascular
      disease. They are involved in the development and progression of atherosclerosis,
      native vessel and graft thrombosis. They have a central role in the development
      of restenosis and reocclusion after peripheral percutaneous transluminal
      angioplasty. Antiplatelet therapy has been shown to be beneficial in patients
      undergoing peripheral vascular surgery or radiological intervention. Yet current
      routine therapy, namely aspirin and dipyridamole are limited in their mode of
      action and efficacy. Recent developments in the understanding of platelet
      function has led to the development of new more potent drugs such as clopidogrel.
      Combination of drugs and more specific investigation of individual platelet
      function may well result in improved bypass and angioplasty patency rates. The
      results of proposed large randomised controlled trials on the role and safety of
      aspirin and clopidogrel are awaited with interest. Given the importance of
      platelets in peripheral vascular disease highlighted in this review, achieving an
      optimal safe anti-platelet effect for each patient with peripheral vascular
      disease should be the target of future research.

PMID- 12525806
TI  - Increased platelet aggregation and activation in peripheral arterial disease.
AB  - OBJECTIVES: patients with peripheral arterial disease (PAD) have a threefold
      increase in cardiovascular mortality. Standard antiplatelet treatment may not
      confer uniform benefit in different patient groups. This study aimed to compare
      platelet function in patients with lower limb PAD, carotid disease and abdominal
      aortic aneurysm (AAA) with age- and sex-matched healthy controls. METHODS:
      patients with lower limb PAD (n = 20), carotid disease (n = 40), AAA (n = 13) and
      age/sex matched healthy controls (n= 20) were studied. Whole blood methods to
      detect spontaneous platelet aggregation (SPA), and adenosine diphosphate (ADP)
      and collagen-induced aggregation were used. The detection of platelet P-selectin
      and the PAC-1 antigen by flow cytometry were also used as markers of platelet
      activation and aggregation. RESULTS: patients with lower limb PAD or AAA had
      higher baseline SPA compared to normal controls (p < 0.01). There was
      significantly higher collagen-induced aggregation in IC patients compared to
      normal controls (p < 0.01). However, there was no difference in ADP-induced
      aggregation between lower limb PAD and control patients. There was no difference
      in PAC-1 binding between control patients and the patients with lower limb PAD,
      carotid disease or AAA. Patients with carotid disease had a higher expression of
      P-selectin compared to normal controls (p < 0.05). CONCLUSIONS: this study
      provides further evidence that platelet hyperactivity is present in patients with
      PAD despite the use of antiplatelet therapy. Further antiplatelet strategies may
      be indicated to protect these patients.

PMID- 12525807
TI  - Ultrasound contrast-agent improves imaging of lower limb occlusive disease.
AB  - OBJECTIVES: to evaluate if ultrasound contrast-agent infusion could improve
      duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the
      agreement with digital subtraction arteriography (DSA). DESIGN: prospective and
      consecutive study. MATERIAL: of 60 consecutive PAD patients, 15 were found to
      have an inconclusive duplex-ultrasound scan of the trifurcation and were included
      in the study. All 15 patients (53% male) were scheduled for DSA, all being
      candidates for vascular surgery due to claudication (n = 3, 20%), rest pain (n =
      5, 33%) and tissue loss (n = 7, 47%). METHODS: on the day before DSA, a duplex
      ultrasound scan of the trifurcation was performed. If the duplex-ultrasound scan
      was found inconclusive, it was repeated during continuous ultrasound contrast
      agent infusion. DSA was performed unaware of the duplex-ultrasound results and
      served as the gold standard. RESULTS: after contrast-agent administration, the
      number of inconclusively diagnosed segments was significantly reduced by 26
      (70%), from 37 to 11(p < 0.001). In 19 segments (73%) contrast-agent infusion
      changed the diagnosis in accordance with the DSA (p < 0.05). Values of
      sensitivity and positive predictive value were improved from 0.20 (0.04-0.62) to
      0.47 (0.26-0.69) and 0.50 (0.10-0.91) to 0.80 (0.49-0.93), respectively.
      Specificity and negative predictive value were unchanged. Agreement between
      duplex-ultrasound and DSA were improved from poor (kappa = 0.18 (95% CI: 0-0.82))
      to moderate (kappa = 0.45 (0.17-0.74)) (p = 0.44). CONCLUSION: ultrasound
      contrast-agents improve the diagnostic ability of duplex-ultrasound when scanning
      difficult arterial segments in patients suffering from PAD.

PMID- 12525808
TI  - Infrainguinal arterial reconstruction for limb salvage in patients with end-stage
      renal disease.
AB  - OBJECTIVES: to evaluate the efficacy of infrainguinal bypass for limb-threatening
      ischaemia in patients with end-stage renal disease (ESRD). MATERIALS AND METHODS:
      from 1991 through 2000, 28 limbs in 22 patients with ESRD received 33
      infrainguinal bypasses, while 65 limbs in 57 patients with functioning kidneys
      underwent 77 bypasses for limb salvage. The prevalence of diabetes is higher in
      the ESRD group (p = 0.03). RESULTS: perioperative mortality and patient survival
      rate in the follow-up period were significantly poorer in patients with ESRD (18%
      vs 0%; p = 0.001, and 45% vs 85%, p < 0.001, respectively). Most causes of death
      were related to atherosclerosis or respiratory diseases. In spite of no
      significant difference in 2-year primary and secondary graft patency rates and
      limb salvage between the ESRD and non-ESRD groups (76% vs 83%; p = 0.12, 85% vs
      91%; p = 0.06, and 83% vs 93%; p = 0.06, respectively), two cases of early limb
      loss occurred as a result of uncontrolled infection in the ESRD group. In
      contrast to autogenous conduits, nonautogenous conduits revealed a poorer outcome
      in ESRD patients (p = 0.03). CONCLUSIONS: perioperative mortality and patient
      survival rate were significantly poorer in the ESRD group. Preoperative full
      evaluation of myocardial and brain ischaemia, revascularisation with autogenous
      conduits, appropriate treatment of wound infection, and strict follow-up for
      accompanying diseases may be needed in these patients.

PMID- 12525809
TI  - Microtibial embolectomy.
AB  - BACKGROUND: microtibial embolectomy is an important technique in cases of limb
      threatening acute arterial occlusion affecting native crural and pedal vessels.
      It is particularly useful when thrombolysis is contraindicated or ineffective as
      in "trash foot". METHODS: in order to evaluate the efficacy of this technique, a
      retrospective case note review was carried out for patients undergoing
      microtibial embolectomy from 1990 to 1999. Data collected included the causes and
      degree of ischaemia, additional procedures required, vessel patency, limb salvage
      and complications encountered. RESULTS: twenty-two limbs underwent exploration of
      the crural/pedal vessels with ankle level arteriotomies under local anaesthetic
      in 12 cases, general anaesthetic in nine and epidural in one. The causes of
      ischaemia were cardiac emboli (8), "trash foot" (7), emboli from aortic and
      popliteal aneurysms (3) and thrombotic occlusion of crural vessels (4). The
      vessel patency rate was 69% and limb salvage rate 62% (13/21) up to 5-years
      follow-up. Six of the seven cases with "trash foot" were salvaged while one
      required an amputation at 3-months post-operatively. The 30-day mortality was 22%
      (5/22). CONCLUSIONS: microtibial embolectomy is effective in acute occlusion of
      the crural/pedal arteries including cases of "trash foot", offering limb salvage
      to a worthwhile proportion of cases.

PMID- 12525811
TI  - Satisfaction with care in vascular surgery inpatient units.
AB  - OBJECTIVE: to identify and solve problems concerning satisfaction of inpatients
      in three different vascular surgery units. MATERIALS AND METHODS: a self
      administered non anonymous questionnaire was submitted. Four dimensions of
      patients' satisfaction and a measure of overall satisfaction were evaluated. For
      each of them a logistic regression model was elaborated. RESULTS: one hundred and
      fifty-six eligible patients agreed to participate. For the "overall satisfaction"
      56% rated the care received as excellent; patients completely satisfied for
      "treatment and related information" were 76%; for the "availability of staff"
      96%, for "helpfulness and communication by staff" 56% and for "management of
      patient's complaint by medical staff" 86%. Logistic regression analysis showed,
      after adjustment for relevant background factors, a statistically significant
      difference among units of care for the overall satisfaction. CONCLUSIONS: the
      study highlighted the importance of considering in vascular units the patients'
      satisfaction as an essential component of quality of care independently of the
      severity of cases. The hospital management recognised the low level of
      communication by the staff as one of the hospital bottle-necks and tried to solve
      a logistic problem identified as responsible for a low score in the overall
      satisfaction in one unit.

PMID- 12525810
TI  - Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.
AB  - OBJECTIVES: intimal hyperplasia (IH) is a major cause of re-stenosis post
      vascular intervention. Induction of heat shock proteins (HSPs), by thermal pre
      conditioning, reduces IH. Our aim was to investigate the effect of the
      pharmacological HSP inducer herbimycin A on IH in the rat carotid balloon injury
      model. MATERIALS AND METHODS: thirty male Sprague-Dawley rats were randomized
      into three groups. All groups underwent balloon injury to the left carotid
      artery. Stress proteins were induced 18 h pre-operatively by heat shock or
      herbimycin A. Two weeks post-operatively, animals were sacrificed and carotid
      intima/media area ratio (I/M ratio) calculated using computerized planimetry. Neo
      intimal proliferation was assessed immunohistochemically with PCNA (proliferating
      cell nuclear antigen). Western blot and immunohistochemistry for arterial HSP70
      and HSP27 were performed. RESULTS: heat stress and herbimycin significantly
      reduced the I/M ratio (p < 0.05 vs balloon injury alone). Neo-intimal
      proliferation was significantly reduced in the heat stress and herbimycin groups
      (p < 0.05 vs balloon injury alone). Heat stress induced arterial HSP70 and HSP27.
      Herbimycin A increased arterial HSP27. CONCLUSION: herbimycin A significantly
      attenuates IH after balloon injury. HSP27 may be the HSP involved in mediating
      this response. Pharmacological inducers of HSPs may have a therapeutic role to
      play in preventing re-stenosis post-vascular intervention.

PMID- 12525812
TI  - Primary varicose veins: the sapheno-femoral junction, distribution of
      varicosities and patterns of incompetence.
AB  - OBJECTIVE: to determine the patterns of long saphenous vein (LSV) disease in
      primary varicose veins (VVs). DESIGN: a retrospective analysis of venous duplex
      scans performed on patients referred for treatment of primary VVs. METHODS:
      analysis was made of sapheno-femoral junction (SFJ) incompetence, non-SFJ
      incompetence, segmental and perforating vein incompetence, distribution of
      varicosities, deep venous insufficiency, and short saphenous incompetence.
      RESULTS: four hundred and eighty-one patients were assessed (median age 50 (range
      12-98) years; male:female ratio 1:1.95), comprising 706 limbs. Forty-six per cent
      of limbs had a competent SFJ, 64% of which had no incompetent perforating vessels
      associated. Disease was more widespread when the SFJ was incompetent.
      Varicosities were most common in the calf, occurring at or below the level of
      incompetence within the LSV. Incompetent segments occurred most commonly above
      knee. There was no obvious correlation between incompetent perforators and
      distribution of varicosities, or incompetent segments. Short saphenous
      incompetence and non-SFJ groin recurrence were associated more with a competent
      SFJ, the converse being true for the Giacomini vein. CONCLUSION: primary VVs
      develop in isolated segments of the superficial venous system (without connection
      to the deep system) at, or distal to, the underlying main trunk incompetence,
      suggesting a process of "spreading incompetence" from one focal point, producing
      varicosities (mainly in tributaries).

PMID- 12525813
TI  - Carotid surgery in acute symptomatic patients.
AB  - OBJECTIVES: evaluation of urgent carotid artery surgery with new diagnostic
      techniques and changing surgical considerations at a university hospital. DESIGN,
      MATERIAL AND METHODS: prospective monitoring and assessment of outcome in 67
      patients who underwent urgent carotid surgery because of symptomatic extracranial
      carotid artery involvement. Patients were examined via the stroke unit: duplex
      sonography was mandatory for diagnosis of extracranial carotid artery disease, as
      was proof of an open middle cerebral artery (MCA). Assessment of intracerebral
      damage followed CT or MR imaging procedures. Perioperative and surgical
      management was standardized. Neurological impairment was assessed pre-,
      postoperatively and at follow-up using the Rankin scale. "Urgent" was defined as
      "immediate" after the final diagnostic step had been performed. RESULTS: within a
      period of 26 months 67 symptomatic patients (58% stroke, 42% TIA) underwent
      urgent carotid surgery. Median time from admission to surgery was 2 days. In all
      but five cases flow through the ICA could technically be restored (93%). Thirty
      day mortality was 3% and disease-related morbidity 13%. The one and two year
      survival rates were 92 and 90%, respectively. No ipsilateral recurrent stroke
      occurred during follow-up. CONCLUSIONS: clinical decision-making based on
      stratified diagnostic workup by means of extra- and intracranial as well as
      intracerebral hemodynamics using new imaging techniques may select patients who
      will benefit more from urgent surgery than from conservative management.

PMID- 12525814
TI  - Low atmospheric pressure is associated with rupture of abdominal aortic
      aneurysms.
AB  - INTRODUCTION: the rate of rupture of abdominal aortic aneurysms (AAAs) has been
      shown to have a seasonal variation with more ruptures occurring during the winter
      months. One of the main meterological changes between the seasons is a change in
      atmospheric pressure. The aim of this study was to investigate whether there was
      any relationship between atmospheric pressure and the incidence of AAA rupture.
      METHODS: all cases of ruptured AAA admitted to a single hospital over a ten year
      period were identified from hospital records. Daily atmospheric pressure readings
      from the nearest weather recording station to the hospital were obtained for the
      same period. Cases were only included if rupture could be confirmed by reviewing
      the patients case-notes. RESULTS: admission rates for ruptured AAA showed a
      monthly variation with the highest rate in December and the lowest in August.
      There was a statistically significant correlation between the number of cases
      admitted in any particular month and the mean atmospheric pressure for the
      previous month. Neither daily minimum, maximum or mean pressure, weekly mean
      pressure or daily pressure variability were significantly different between those
      days when a ruptured AAA was admitted and those when no ruptured AAA was
      admitted. CONCLUSIONS: low atmospheric pressure is associated with increased rate
      of AAA rupture. The method by which this change in pressure precipitates rupture
      cannot be determined from this study.

PMID- 12525815
TI  - A porcine model of systemic and renal haemodynamic responses to infrarenal aortic
      cross-clamping.
AB  - OBJECTIVES: cross-clamping of the infrarenal aorta is associated with complex
      haemodynamic disturbances. Several experimental models of aortic cross-clamping
      (AXC) have been described with heterogeneous results. The main purpose of this
      study was to establish an animal model in which infrarenal AXC could reproduce
      similar systemic and renal haemodynamic changes to those observed in humans.
      METHODS: eleven anaesthetised pigs underwent AXC just below the renal arteries.
      Renal blood flow was measured using clearance of (131)I hippuran. Systemic and
      renal parameters were collected at 3 consecutive 30-min periods. RESULTS: AXC did
      not alter the extraction fraction of (131)I hippuran but was accompanied by
      significant (13%) decrease in cardiac index (p = 0.005) and a 23% increase in
      mean arterial pressure (p = 0.005). AXC induced significant 135% increase in
      renal vascular resistance (p = 0.012) and a 35% decrease in renal blood flow (p =
      0.016). This worsened after removal of the aortic clamp, whereas systemic
      variables returned to baseline levels. CONCLUSIONS: this AXC animal model
      reproduces the changes observed in humans. It provides a reliable animal model
      which allows to investigate the underlying mechanisms of renal vasoconstriction
      and the effect of new drugs.

PMID- 12525816
TI  - Atherosclerotic popliteal aneurysms: management and outcome in forty-six
      patients.

PMID- 12525817
TI  - The anatomical distribution of iliac aneurysms: is there an embryological basis?

PMID- 12525818
TI  - Major bleeding and severe thrombocytopenia after combined heparin and abciximab
      c7E3 Fab therapy.

PMID- 12525819
TI  - Perforator reflux and clinical presentation in primary superficial venous
      insufficiency.

PMID- 12525820
TI  - Deep vein thrombosis in azygos continuation.

PMID- 12525821
TI  - The use of alternative sources of autologous vein for infrainguinal bypass.

PMID- 12525824
TI  - The role of platelets in decrypting monocyte tissue factor.
AB  - Although about 80% of tissue factor (TF) extracellular domain antigen present in
      lipopolysaccharide (LPS)-stimulated monocytes is available at the cell surface,
      only 10% to 20% of the total extractable TF activity is expressed on the surface
      of intact monocytes. Thus, most of the TF activity is latent or encrypted in the
      cell membrane. When coincubated, leukocytes and platelets generate more TF
      activity than either cell type alone. We have shown that such platelet-promoted
      enhancement of LPS-induced TF activity in monocytes in whole blood depends on
      neutrophil involvement in a P-selectin/CD15 (a leukocyte membrane-bound
      carbohydrate)-dependent reaction. The effect was even more pronounced when both
      the phorbol ester, phorbol 12-myristate 13-acetate (PMA), and LPS were present
      during monocyte stimulation. We currently envisage that decryption is mediated
      through the secretion of TF-rich particles by monocytes. These particles express
      CD15 and bind P-selectin exposed on either activated platelets or platelet
      derived microparticles. Interactions and fusion events, that typically occur
      between monocytes and platelets, would facilitate the generation of
      monocytes/monocyte microparticle and platelets/platelet microparticle hybrids,
      leading to particles rich in decrypted TF activity. In conclusion, platelets play
      a pivotal role in decrypting TF activity of monocytes, generating a hybrid TF
      terrain, which both triggers and favors thrombogenesis.

PMID- 12525825
TI  - The action of high-dose factor VIIa (FVIIa) in a cell-based model of hemostasis.
AB  - We have developed a cell-based model of hemostasis. This model suggests that the
      defect in hemophilia is specifically a failure of platelet-surface factor Xa
      (FXa) generation, leading to a failure of platelet surface thrombin generation.
      Activation of FX by FVIIa/tissue factor (TF) does not compensate for a lack of
      FXa activation on the platelet surface by the FVIIIa/FIXa complex. This is
      because plasma protease inhibitors prevent FXa from moving through the fluid
      phase from the TF-bearing cell to the platelet surface. We have previously
      proposed a platelet-dependent mechanism of action for high-dose factor VIIa
      (FVIIa; Novoseven, Novo Nordisk, Copenhagen, Denmark). Our data suggest that,
      when present at high levels, FVIIa binds to activated platelets and activates
      small amounts of FX independent of TF. This platelet-surface FXa can partially
      restore platelet-surface thrombin generation in hemophilia. Recently, van't Veer
      and colleagues reported results from an in vitro model in which coagulation
      reactions were initiated by relipidated TF. The authors concluded that high-dose
      FVIIa may exert a hemostatic effect in hemophilia by overcoming inhibition of
      FVIIa/TF activity by zymogen FVII. By contrast, we found that plasma levels of
      FVII did not slow thrombin generation in a model system initiated with cell
      associated TF. This discrepancy highlights the potential differences between the
      studies of the coagulation reactions assembled on living cells compared to
      phospholipid vesicles. Our data suggest that in a cellular system high-dose FVIIa
      acts primarily by enhancing the rate of thrombin generation on platelet surfaces
      and not by overcoming inhibition by zymogen FVII of TF-dependent activation of
      FX.

PMID- 12525826
TI  - Inhibitor treatment: state of the art.
AB  - The treatment of hemophilic patients with inhibitors presents many challenges.
      Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen,
      Denmark) is a new therapeutic option for this patient population. Optimization of
      dosing regimens may be achieved by considering (1) individual pharmacokinetics
      (especially in the pediatric population); (2) high-dose bolus regimens; (3)
      continuous infusion (CI) including high-dose CI; (4) early treatment with
      NovoSeven in the course of a bleeding event; and (5) use of NovoSeven as a
      prophylactic therapy. The literature involving these issues is reviewed here.
      Institution of early therapy has been shown to decrease total NovoSeven
      requirement while increasing efficacy. Pediatric patients may require a higher
      dose of NovoSeven due to the higher clearance rate and shorter half-life
      demonstrated by this population. Therefore, the patient's age and/or individual
      pharmacokinetics and clearance rate should be considered when calculating doses
      and CI rates. High-dose NovoSeven has been shown to be effective in some patient
      populations without increased reported adverse events. Despite its short half
      life, prophylactic use of NovoSeven has been reported in a small number of
      patients, with an apparent decrease in bleeding episodes experienced. There has
      been significant interest in administration of NovoSeven by CI, particularly in
      patients requiring prolonged treatment, and it has been shown to be successful,
      although the optimal target factor VII activity has yet to be established and
      some authors have recommended the use of concomitant antifibrinolytics.

PMID- 12525827
TI  - Recombinant factor VIIa (NovoSeven) as a hemostatic agent.
AB  - Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Denmark)
      induces hemostasis in life- and limb-threatening bleeds and in major surgery of
      hemophilia A and B patients, regardless of inhibitor titer. A total of more than
      6,500 patients have been treated, and NovoSeven has been administered in more
      than 180,000 standard doses. Experience gained from these clinical situations
      suggests that NovoSeven should be administered as a 90- to 110-microg/kg bolus
      dose every second hour. Hemophilia patients with mild to moderate bleeding
      episodes require two to three doses to achieve complete hemostasis, whereas
      patients with severe bleeding episodes may require more doses. For major surgery
      and in cases of life-threatening bleeding, dosing every second hour for the first
      24 hours may be required. Thereafter, the same dose, but with longer intervals
      between doses, is recommended. Recent in vitro experiments indicate that even
      higher doses of NovoSeven may be needed to achieve full thrombin generation in
      the absence of factor VIII (FVIII), factor IX (FIX), and factor XI (FXI).

PMID- 12525828
TI  - Immunotherapy. Oral route to Holy Grail?

PMID- 12525832
TI  - Increased receptor-mediated gene delivery to the liver by protamine-enhanced
      asialofetuin-lipoplexes.
AB  - A novel lipidic vector composed of DOTAP/Chol liposomes, asialofetuin (AF),
      protamine sulfate and DNA has been developed. The resulting protamine-AF
      lipoplexes improved significantly the levels of gene expression in cultured cells
      and in the liver upon i.v. administration. Lipoplexes containing the optimal
      amount of AF (1 microg/microg DNA) showed a 16-fold higher transfection activity
      in HepG2 cells than non-targeted (plain) complexes. The uptake by cells having
      asialoglycoprotein receptors (ASGPr) on their plasma membrane was decreased by
      the addition of free AF, indicating that AF-lipoplexes were taken up specifically
      by cells via ASGPr-mediated endocytosis. Results from transfections performed in
      cells defective in ASGPr, ie HeLa cells, confirmed this mechanism. By addition of
      the condensing peptide, protamine sulfate, smaller complexes were obtained, which
      enhanced even more the uptake of AF-complexes in HepG2 cells and in the liver.
      The optimal amount of protamine was 0.4 microg/mcirog DNA, and gene expression
      was about 5-fold over that obtained with AF-lipoplexes in the absence of the
      peptide, and 75-fold higher than that with plain conventional lipoplexes.
      Protamine-AF-lipoplexes increased by a factor of 12 luciferase gene expression in
      the liver of mice administered systemically via the tail vein, compared to plain
      complexes. In summary, our findings extend the scope of previous studies where AF
      lipoplexes were used to introduce DNA into hepatocytes. The combination of
      targeting and protamine condensation obviated the need for partial hepatectomy,
      commonly required to obtain efficient gene delivery in this organ. Since
      protamine sulfate has been proven to be non-toxic in humans, the novel liver
      specific vector described here may be useful for the delivery of clinically
      important genes to this organ.

PMID- 12525833
TI  - beta-cell neogenesis induced by adenovirus-mediated gene delivery of
      transcription factor pdx-1 into mouse pancreas.
AB  - beta-cell neogenesis is expected to provide a new therapy for diabetes. Numerous
      studies have demonstrated that transcriptional regulation involving pdx-1 is
      essential for endocrine neogenesis in vivo and in vitro. Therefore, it is
      possible that ectopic expression of pdx-1 in the pancreas could induce endocrine
      neogenesis. To test this possibility, we performed safe and efficient gene
      delivery of the pdx-1 gene into the mouse pancreas through the common bile duct
      using adenoviral vectors, and examined the effects of the ectopic expression of
      pdx-1. Here we show that adenovirus-mediated expression of pdx-1 can activate the
      endogenous pdx-1 gene, leading to beta-cell neogenesis and ductal proliferation.
      This technique is similar to the endoscopic retrograde cholangiopancreatography,
      which has been already established as a safe procedure for humans. Thus, beta
      cell neogenesis induced by adenovirus-mediated expression of pdx-1 provides a
      novel strategy for gene therapy for a cure for diabetes mellitus.

PMID- 12525834
TI  - Oligonucleotide-directed single-base DNA alterations in mouse embryonic stem
      cells.
AB  - We have investigated the use of single-stranded oligodeoxy-nucleotides (ssODN) to
      produce specific single-base alterations in episomal and chromosomal DNA in mouse
      embryonic stem (ES) cells. Two different reporter genes, EGFP and LacZ, each with
      a single point mutation that inactivates reporter activity, were used. ssODN
      homologous to the target sequence, except for a single mismatch at the mutant
      base, were used to correct the mutant reporter genes. When tested in CHO-K1
      cells, the ssODN showed correction rates of 0.5-1.0%, consistent with prior
      reports. ssODN in the antisense orientation provided higher rates of gene
      conversion than those in the sense orientation for both reporter genes. Nuclear
      extracts from mouse ES cells exhibited nearly the same correction activity as
      extracts from CHO-K1 cells. ssODN corrected the mutant bases of both episomal and
      chromosomal mutant reporter genes in mouse ES cells. Although the efficiency of
      gene correction observed in ES cells is low, approximately 10(-4), these results
      demonstrate that ssODN can produce single-base alterations in the genomic DNA of
      mouse ES cells. As conversion efficiency is improved by the continued development
      of oligonucleotide structure and DNA delivery methods, ssODN could be used to
      produce ES cells with specific mutations in any gene in a single step. The
      targeted ES cells could in turn be used to create accurate mouse models of
      inherited diseases.

PMID- 12525835
TI  - Viral-mediated delivery of the late-infantile neuronal ceroid lipofuscinosis
      gene, TPP-I to the mouse central nervous system.
AB  - Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is caused by
      mutations in tripeptidyl peptidase I (TPP-I), a pepstatin-insensitive lysosomal
      protease, resulting in neurodegeneration, acute seizures, visual and motor
      dysfunction. In vitro studies suggest that TPP-I is secreted from cells and
      subsequently taken up by neighboring cells, similar to other lysosomal enzymes.
      As such, TPP-I is an attractive candidate for enzyme replacement or gene therapy.
      In the present studies, we examined the feasibility of gene transfer into mouse
      brain using recombinant adenovirus (Ad), feline immunodeficiency virus (FIV) and
      adeno-associated virus (AAV) vectors expressing TPP-I, after single injections
      into the striatum or cerebellum. A dual TPP-I- and beta-galactosidase-expressing
      adenovirus vector (AdTTP-I/nlsbetagal) was used to distinguish transduced (beta
      galactosidase positive) cells from cells that endocytosed secreted TTP-I. Ten
      days after striatal injection of AdTTP-I/nlsbetagal, beta-galactosidase-positive
      cells were concentrated around the injection site, corpus callosum, ependyma and
      choroid plexus. In cerebellar injections, beta-galactosidase expression was
      confined to the region of injection and in isolated neurons of the brainstem.
      Immunohistochemistry for TPP-I expression showed that TPP-I extended beyond areas
      of beta-galactosidase activity. Immunohistochemistry for TTP-I after FIVTTP-I and
      AAV5TTP-I injections demonstrated TPP-I in neurons of the striatum, hippocampus
      and Purkinje cells. For all three vectors, TPP-I activity in brain homogenates
      was 3-7-fold higher than endogenous levels in the injected hemispheres. Our
      results indicate the feasibility of vector-mediated gene transfer of TPP-I to the
      CNS as a potential therapy for LINCL.

PMID- 12525836
TI  - Seminiferous tubule cannulation (STC): a new, sensitive technique for detecting
      gene transfer in developing sperm.
AB  - As gene therapy vectors, strategies, and disease targets continue to expand and
      diversify, the likelihood that developing germ cells will be exposed to gene
      transfer vectors increases. Insertion of exogenous genetic material into the germ
      line might have devastating effects on normal development which could be
      heritable. Accordingly, it is important that vectors be tested for their
      potential to insert genes into developing gametes. Such tests are most difficult
      in males, where differentiating sperm are sequestered behind the blood-testis
      barrier. In this communication we report the development of a new technique,
      which we call seminiferous tubule cannulation (STC). We demonstrate that STC
      allows delivery of high quantities of gene therapy vector directly to
      spermatogenic cells without significantly disturbing the cytoarchitecture of the
      seminiferous tubule. To demonstrate the effectiveness of this technique, three
      promoters driving lacZ gene expression in adenovirus vectors were tested for
      their ability to transduce cells within the seminiferous tubule. Results indicate
      that the cytomegalovirus promoter, but not the Rous sarcoma virus or elongation
      factor 1alpha promoters, is active within the seminiferous tubule. Further
      development of this technique promises to lead to a standardized test for male
      germ cell transduction by gene therapy vectors.

PMID- 12525837
TI  - Suicide gene therapy using AAV-HSVtk/ganciclovir in combination with irradiation
      results in regression of human head and neck cancer xenografts in nude mice.
AB  - The application of adeno-associated virus (AAV) vectors to cancers is limited by
      their low transduction efficiency. Previously, we reported that gamma-ray
      enhanced the second-strand synthesis, leading to the improvement of the transgene
      expression, and cytocidal effect of the herpes simplex virus type-1 thymidine
      kinase (HSVtk) and ganciclovir (GCV) system. In this study, we extended this in
      vitro findings to in vivo. First, the laryngeal cancer cell line (HEp-2) and HeLa
      were treated with AAVtk/GCV, the number of surviving cells was reduced as the
      concentration of GCV increased. Furthermore, the 4 Gy irradiation enhanced the
      killing effects of AAVtk/GCV by four-fold on HeLa cells and 15-fold on HEp-2
      cells. Following the in vitro experiments, we evaluated the transgene expression
      and the antitumor activity of the AAV vectors in combination with gamma-ray in
      nude mice inoculated with HEp-2 subcutaneously. The LacZ expression was observed
      in the xenografted tumors and significantly increased by gamma-ray. The AAVtk/GCV
      system suppressed the tumors growth, and gamma-ray augmented the antitumor
      activity by five-fold. These findings suggest that the combination of AAVtk/GCV
      system with radiotherapy is significantly effective in the treatment of cancers
      and may lead to reduction of the potential toxicity of both AAVtk/GCV and gamma
      ray.

PMID- 12525838
TI  - Novel antisense oligonucleotides targeting TGF-beta inhibit in vivo scarring and
      improve surgical outcome.
AB  - The scarring response is an important factor in many diseases throughout the
      body. In addition, it is a major problem in influencing results of surgery. In
      the eye, for example, post-operative scarring can determine the outcome of
      surgery. This is particularly the case in the blinding disease glaucoma, where
      several anti-scarring regimens are currently used to improve glaucoma surgery
      results, but are of limited use clinically because of severe complications. We
      have recently identified transforming growth factor-beta (TGF-beta) as a target
      for post-operative anti-scarring therapy in glaucoma, and now report the first
      study of novel second-generation antisense phosphorothioate oligonucleotides
      against TGF-beta in vivo. Single applications of a TGF-beta OGN at the time of
      surgery in two different animal models closely related to the surgical procedure
      performed in glaucoma patients, significantly reduced post-operative scarring
      (P<0.05) and improved surgical outcome. Our findings suggest that TGF-beta
      antisense oligonucleotides have potential as a new therapy for reducing post
      surgical scarring. Its long-lasting effects after only a single administration at
      the time of surgery make it particularly attractive clinically. Furthermore,
      although we have shown this agent to be useful in the eye, it could have
      widespread applications anywhere in the body where the wound-healing response
      requires modulation.

PMID- 12525839
TI  - Enhanced cytosolic delivery of plasmid DNA by a sulfhydryl-activatable
      listeriolysin O/protamine conjugate utilizing cellular reducing potential.
AB  - Listeriolysin O (LLO), a sulfhydryl-activated pore-forming protein from Listeria
      monocytogenes, was tested and utilized for promoting plasmid DNA (pDNA) delivery
      into the cytosol of cells in culture. To render pDNA-complexing capability to
      LLO, the unique cysteine 484 of LLO was conjugated to polycationic peptide
      protamine (PN) at a 1:1 molar ratio through a reversible, endosome-labile
      disulfide bond. The sulfhydryl-oxidized LLO construct, LLO-s-s-PN, completely
      lacked its pore-forming activity, yet regained its original activity upon
      reduction. The enhanced cytosolic delivery using this construct therefore relies
      on the requisite reduction of the disulfide bond in LLO-s-s-PN by endogenous
      cellular reducing capacity. Condensed PN/pDNA complexes incorporating LLO-s-s-PN
      were tested for their enhanced gene delivery capability monitoring reporter gene
      expression in HEK293, RAW264.7, P388D1 cell lines and bone-marrow-derived
      macrophages in the presence of serum. Dramatic enhancement was observed for all
      tested complexes with varying weight ratios. The effect was most prominent at
      0.64-0.80 (w/w) of PN/pDNA upon replacing 1-4% of PN with LLO-s-s-PN, resulting
      in approximately three orders of magnitude higher luciferase expression compared
      to PN/pDNA without apparent toxicity. These results demonstrate that
      incorporation of endosomolytic LLO into pDNA delivery systems in a controlled
      fashion is a promising approach of enhancing delivery into the cytosol of target
      cells in gene delivery strategies.

PMID- 12525841
TI  - [Acute appendicitis in the laparoscopic surgery era].

PMID- 12525840
TI  - Tetracycline-inducible transgene expression mediated by a single AAV vector.
AB  - Regulated gene delivery systems are usually made of two elements: an inducible
      promoter and a transactivator. In order to optimize gene delivery and regulation,
      a single viral vector ensuring adequate stoichiometry of the two elements is
      required. However, efficient regulation is hampered by interferences between the
      inducible promoter and (i) the promoter used to express the transactivator and/or
      (ii) promoter/enhancer elements present in the viral vector backbone. We describe
      a single AAV vector in which transcription of both the reverse tetracycline
      transactivator (rtTA) and the transgene is initiated from a bidirectional
      tetracycline-responsive promoter and terminated at bidirectional SV40
      polyadenylation sites flanking both ITRs. Up to 50-fold induction of gene
      expression in human tumor cell lines and 100-fold in primary cultures of rat
      Schwann cells was demonstrated. In addition an 80-fold induction in vivo in the
      rat brain has been obtained. In vitro, the autoregulatory vector exhibits an
      induced expression level superior to that obtained using the constitutive CMV
      promoter. Although extinction of the transgene after removal of tetracycline was
      rapid (less than 3 days), inducibility after addition of tetracycline was slow
      (about 14 days). This kinetics is suitable for therapeutic gene expression in
      slowly progressive diseases while allowing rapid switch-off in case of
      undesirable effects. As compared to previously described autoregulatory tet
      repressible (tetOFF) AAV vectors, the tet-inducible (tetON) vector prevents
      chronic antibiotic administration in the uninduced state.

PMID- 12525842
TI  - [Microscopic colitis in patients with chronic diarrhea].
AB  - It has recently been suggested that there is an association between infectious
      gastroenteritis and irritable bowel syndrome with chronic diarrhea; and a
      striking similarity between the microscopic lesion observed in this condition and
      the lesion described in microscopic colitis (MC). As in developed countries MC is
      found in only 12.6 to 15% of patients with chronic diarrhea, we thought it
      worthwhile to investigate in Peru, a developing country with high prevalence of
      infectious gastroenteritis, the prevalence of MC also in patients with chronic
      diarrhea. One hundred and ten patients with chronic diarrhea underwent biopsies
      from the right and left colon, and the biopsies were examined histologically to
      detect MC of lymphocytic or collagenous type.MC was present in 44 (40%) of the
      110 patients with chronic diarrhea, being of lymphocytic type in 42, and of
      collagenous type in. The prevalence of MC observed in Peruvian patients with
      chronic diarrhea is high when compared to reports from developed countries. This
      finding supports the idea that infectious gastroenteritis may, under certain
      conditions, precipitate the appearance of MC, probably by an autoimmune reaction.

PMID- 12525843
TI  - [The validity of the proteins concentrations in the ascitic liquid and serum for
      the differential diagnosis of the ascitis].
AB  - Prospective evaluation was performed in 60 in-patients, carriers of ascites of
      different etiologies, analyzing the validity of the parameters depending on
      protein and albumin dosage, both in the ascitic serum and fluid, for the
      discrimination of possible etiological causes of ascites, including in these
      parameters Protein Concentration in the Ascitic Fluid, the Serum-Ascites Albumin
      Gradient, the Protein Ascites/Serum Ratio, and the Albumin Concentration in the
      ascitic fluid. Average age was 46.9 +/- 19.6, all female; 21 cases were
      associated with Chronic Hepatic Disease, 14 to Tuberculosis, 11 to Malignant
      Neoplasia, 7 to Nephrotic syndrome, 4 to Congestive Heart Failure, 2 to Collagen
      Disease, and 1 to a severe Malnutrition case. The evaluation parameters correlate
      with the oncotic and hydrostatic pressures of the Starling Law, on the basis of
      what they could be compared with, demonstrating that their sensitivity levels and
      their specificity may be used as positive or negative predictive values in the
      discriminative evaluations of ascites in relation to its probable etiological
      causes. Even though the Serum-Ascites Albumin Gradient may be useful in the
      separation of ascites cases with portal hypertension, it is also useful for
      classifying exudates and transudates. However, the other parameters must not be
      excluded for the evaluation of those cases, aiming at establishing whether the
      peritoneum has been affected and hence the terms transudates and exudates should
      still be used on the basis of the high sensitivity value and specificity of
      theses tests, which do not differentiate them statistically from the Serum
      Ascites Albumin Gradient. Using the cut-off points for each parameter, the most
      adequate for our population would be 1.5 gr/dl for Albumin and 2.5 gr/dl for
      protein, with the additional lower cost benefit.

PMID- 12525844
TI  - [Comparative evaluation of the surgical treatment of acute appendicitis: open
      appendicetomy versus laparoscopic appendicectomy in the national hospital
      hospital Carlos a. Seguin e. Essalud].
AB  - STATE OF THE PROBLEM: To establish the advantages and disadvantages of open
      appendicectomy versus laparoscopic appendicectomy in the surgical treatment of
      acute appendicitis in the National Hospital Carlos Alberto Seguin Escobedo.
      OBJECTIVES/AIMS: Comparative evaluation of open appendicectomy versus
      laparoscopic appendicectomy in their grouped in: a) Characters/Features.- Age,
      sex, occupation, time of disease, symptoms and signs, laboratory investigations,
      pre and post operative diagnoses, pre and post operative antibiotic therapy and
      time of anesthesia, b) Impact of surgical techniques in: preoperative time,
      operative time, operative accidents, stay in hospital and postoperative
      complications, and c) Evaluation of the benefits through comparative costs of
      both techniques. Survey Material. It was made/done a comparative survey of 100
      cases/events of open Apendicectomy versus 100 cases/events of Laparoscopic
      Appendicectomy. RESULTS: In the comparative evaluation of both surgical
      techniques there is not significant difference in: age, time of disease, time of
      waiting before the operation, stay in hospital, postoperative complications.
      There are significant difference in: sex, more frequency in female in
      laparoscopic appendicectomy; general anesthesia more frequent in laparoscopic
      appendicectomy; longer operative time in laparoscopic appendicectomy (103.03
      min); higher total cost on average in laparoscopic appendicectomy (2047.97 new
      soles) conversion index laparoscopic appendicectomy 4% CONCLUSION: Laparoscopic
      appendicectomy does not offer significant benefits over open appendicectomy in
      patients with acute appendicitis with the exception of the esthetic aspect in
      women and disadvantages langer operative time and more expensive.

PMID- 12525845
TI  - [Surgical technique for the treatment of the serious acute necrotic pancreatitis
      in the National Hospital Edgardo Rebagliati Martins].
AB  - A surgical technique for the treatment of severe acute pancreatitis with necrosis
      is presented as an alternative in the surgical treatment of this pathology; 60
      patients underwent a surgery by the author et al. between October 1997 and
      January 2002, at the National Hospital Edgardo Rebagliati Martins, Lima, Peru.
      The mortality rate was 25%.

PMID- 12525846
TI  - [Distribution of entero-parasitic infections in the Peruvian Highland: study
      carried out in six rural communities of the department of Puno, Peru].
AB  - A prevalence study was carried out in six rural communities in the Peruvian
      Highlands with the purpose of achieving a better understanding of the
      distribution of entero-parasites. The communities were located along the banks of
      Lake Titicaca, in the provinces of Puno and El Collao, Department of Puno, Peru,
      at 3,800 m.a.s.l. To that effect, a total of 91 feces samples of adults and
      children from the following communities were analyzed: Conchaca, Punutani,
      Capalla, Culta, Maraesquena, and Jaillihuaya. Analysis techniques included Direct
      Examination, Kato Technique, Technique of Spontaneous Sedimentation in a Test
      Tube and the Lumbreras Rapid Sedimentation Technique. The general prelavence of
      intestinal parasitosis was found to be 91.2%. The pathogenic entero-parasites
      found were, in order of frequency, as follows: Hymenolepis nana 6.6%, Entamoeba
      histolytica 5.5%, Giardia lamblia 3.3%, Taenia sp. 2.2%, Ascaris lumbricoides
      2.2%, Trichuris trichiura 1.1%, and Enterobius vermicularis 1.1%. The frequency
      of the non-pathogenic entero-parasites was as follows: Entamoeba coli 78%,
      Endolimax nana 39.6%, Iodamoeba butschlii 14.3%, Blastocystis hominis 9.9%, and
      Chilomastix mesnili 2.2%. Most of the patients had poly parasitism (58.2%), and
      protozoan infections prevailed over helminthic infection. From the total number
      of patients infected, 41.8% had one parasite, 33.0% had two parasites, 11.0% had
      three parasites, 4.4% had four parasites, and 1.1% had five parasites. These
      results show the high rates of parasitism in the rural population on the banks of
      Lake Titicaca, which would be associated with socioeconomic factors and the poor
      environmental sanitation conditions in this area.

PMID- 12525847
TI  - [Mortality due to digestive and hepatobiliary diseases in Peru, 1995 - 2000].
AB  - Digestive diseases in Peru account for the second cause of mortality and
      malignant tumors of the digestive tract rank the third place. It was therefore
      proposed to study the mortality rates for each digestive and hepatobiliary
      disease and establish their frequency and geographical distribution in Peru.
      MATERIALS AND METHODS: Diagnostic information was obtained from death
      certificates in the Information Technology and Statistics Office of the Ministry
      of Health (MINSA) from 1995 to 2000. Mortality rates were determined for 100,000
      inhabitants. The rates obtained were classified in general figures for each year,
      dividing the data in three groups: non-tumoral digestive diseases (esophageal and
      gastrointestinal, gall bladder and pancreas diseases) tumoral diseases
      (esophageal and gastrointestinal, pancreas, gall bladder and biliary tract, liver
      and intrahepatic biliary tract diseases) and liver diseases (liver cirrhosis,
      primary liver malignant tumors and acute viral hepatitis). The first five
      mortality causes were determined for each year for the national population,
      classifying them according to the disease types and heir geographical
      distribution by Department. RESULTS: The first five causes for each year are
      liver cirrhosis (mortality rate: 6.53 - 10.64), malignant stomach tumors
      (mortality rate: 8.7 - 10.36), liver and biliary tract malignant tumors
      (mortality rate: 2.19 - 3.96), malignant colon tumor (2.03 - 2.06), gall bladder
      malignant tumors (1.66 - 1.7), pancreatic tumors (1.60 - 1.75), and gastric ulcer
      (1.27). Amongst tumoral diseases, gastric cancer has the highest mortality rate
      and pancreatic tumors are within the top five causes of death. Amongst liver
      diseases, liver cirrhosis has the highest mortality rate, which correlates with
      the high prevalence of viral hepatitis B in certain areas of Peru. CONCLUSION:
      Amongst digestive diseases, the main causes of death in Peru are liver cirrhosis,
      malignant stomach tumors, liver metastases, gall bladder and pancreas and colon
      malignant tumors. Thus, it is necessary to corroborate these findings with
      epidemiological studies.

PMID- 12525848
TI  - [Granulomatous tuberculous hepatitis as cause of fever of unknown origin].
AB  - The clinical case of one patient with fever of unknown origin, due to
      granulomatous hepatitis of tuberculous etiology was presented. The patient was a
      a 50-year-old woman, with 50 days illness characterized by chills, 39 degrees C
      fever and heavy diaphoresis. She had a record of seven malaria cases. She looked
      thin and pale at the initial physical examination. During the evolution, she
      developed pancytopenia, massive hepatosplenomegaly, jaundice, and anasarca. The
      patient underwent screening tests for infection, neoplasias, collagenosis, and
      granulomatous diseases. The laboratory tests showed transaminase-alkaline
      phosphatase dissociation, which led to the final diagnosis of tuberculosis,
      through the histological examination of the liver parenchyma. The specific
      treatment against tuberculosis caused remission of fever, ascites, and
      hepatomegaly and normalization of liver tests, with satisfactory clinical
      evolution.

PMID- 12525849
TI  - Substrate channelling in a creatine kinase system of rat skeletal muscle under
      various pH conditions.
AB  - The aim of this study was to evaluate myofibrillar creatine kinase (CK) activity
      and to quantify the substrate channelling of ATP between CK and myosin ATPase
      under different pH conditions within the integrity of myofibrils. A pure
      myofibrillar fraction was prepared using differential centrifugation. The
      homogeneity of the preparation and the purity of the fraction were confirmed
      microscopically and by enzymatic assays for contaminant enzyme activities. The
      specific activity of myofibrillar CK reached 584 +/- 33 nmol PCr min(-1) mg(-1)
      at pH 6.75. Two methods were used to detect CK activity: (1) measurement of
      direct ATP production, and (2) measurement of PCr consumption. This method of
      evaluation has been tested in experiments with isolated creatine kinase. No
      discrepancy in CK activity between the methods was observed in the pH range
      tested (6.0-7.5). However, the same procedures resulted in a significant
      discrepancy between the amounts of reacted PCr and produced ATP within the pure
      myofibrillar fraction. This discrepancy represents the portion of ATP produced by
      the CK reaction, which is preferentially channelled to the myosin ATPase before
      diffusing into the bulk solution. The maximum evaluated difference reached 42.3 %
      at pH 6.95. The substrate channelling between myofibrillar-bound CK and myosin
      ATPase was evaluated under various pH levels within the physiological range and
      it reached a maximum value in a slightly acidic environment. These results
      suggest that ATP/ADP flux control by the CK system is more important at lower pH,
      corresponding to the physiological state of muscle fatigue.

PMID- 12525850
TI  - Constitutive secretion of immunoglobulin A and other proteins into lumina of
      unstimulated submandibular glands in anaesthetised rats.
AB  - Salivary fluid secretion is dependent upon reflex stimuli mediated by autonomic
      nerves. In order to determine if immunoglobulin A (IgA) and salivary proteins are
      secreted in the absence of nerve stimulation, small volumes (< 2 microl) of
      saliva were consecutively collected from the submandibular duct of anaesthetised
      rats following rest pauses in order to sample the protein contents of the ductal
      system. Within the first 5 microl of such saliva collected by parasympathetic
      nerve stimulation, IgA and other salivary proteins reached peak concentrations
      that were over 20-fold greater than levels in parasympathetically stimulated
      saliva subsequently collected during a 5 min period of stimulation. Confocal
      microscopy of TRITC-labelled IgA added to live, acutely isolated submandibular
      acini indicated that it did not enter the lumina by paracellular leakage. IgG is
      thought to enter saliva by paracellular leakage but did not accumulate in luminal
      saliva in the present study. Electrophoresis suggested that the major proteins
      secreted in the absence of stimulation were the same as those present in
      subsequently stimulated saliva. It can be concluded that IgA and other major
      submandibular proteins are secreted into glandular lumina in the absence of nerve
      stimulation. The functional significance of such unstimulated protein secretion
      is at present unclear.

PMID- 12525851
TI  - Tetrodotoxin block of A-fibre conduction and its effect on reflex responses
      evoked by electrical stimulation of the sural nerve in the decerebrated rabbit.
AB  - In the present study, we have investigated the viability of using tetrodotoxin
      (TTX) to induce selective blockade of myelinated fibre conduction in rabbit sural
      nerve, and explored some aspects of reflexes evoked by non-myelinated sural nerve
      afferents before and after application of TTX. In rabbits decerebrated under
      halothane-nitrous oxide anaesthesia, application of 30 nM TTX to the desheathed
      sural nerve completely blocked Abeta and Adelta waves of the compound action
      potential evoked by electrical stimulation of the nerve at 95 times threshold.
      The amplitude of C-fibre volleys evoked by these stimuli was reduced to a mean of
      60 % of pre-treatment values. Reflexes evoked in medial gastrocnemius
      motoneurones by sural nerve stimulation showed corresponding changes after TTX
      treatment, with activation latency increasing from 5-7 ms in the control state to
      > 100 ms after TTX application. Temporal summation (wind up) in long latency
      reflexes (> 100 ms) was significantly enhanced after application of TTX. These
      data show that low concentrations of TTX can selectively block conduction in
      rabbit sural nerve A-fibres, providing a method for studying the central actions
      of non-myelinated C-fibres in isolation.

PMID- 12525852
TI  - Autonomous activity in the isolated guinea pig bladder.
AB  - Phasic changes in pressure have been reported to occur in the bladder which are
      not associated with micturition. Spontaneous intravesical pressure changes can be
      recorded from bladders in vitro or bladders in vivo isolated from the central
      nervous system suggesting that the bladder itself is capable of autonomous
      activity. Experiments using isolated cells and muscle strips indicate that the
      smooth muscle can generate spontaneous activity. Whether this is the origin of
      phasic changes in the intact organ remains unknown. The present study set out to
      establish the presence and characteristics of autonomous activity in the isolated
      guinea pig bladder. Multiple-point motion analysis and concurrent intravesical
      pressure recording were used to identify and quantify spontaneous and evoked
      activity. Highly complex autonomous activity was observed in unstimulated
      bladders. This activity comprised localised micro-contractions in single or
      multiple discrete regions, waves of activity and micro-stretches. Low-amplitude
      phasic 'micro-transients' were seen in the intravesical pressure trace in
      association with micro-contractions. Incremental increases in the intravesical
      volume recruited additional areas of activity. Atropine and tetrodotoxin had no
      effect on the micro-transients or micro-contractions. Exposure to the muscarinic
      agonist arecaidine (10-300 nM) initially increased the incidence of micro
      contractions which subsequently became co-ordinated into phasic pressure rises
      and contraction waves, interspersed with periods of total quiescence. The
      findings describe the generation and co-ordination of autonomous activity in the
      bladder wall and also demonstrate complex phasic activity. This approach has
      shown the importance of assessing the integrative properties of the entire organ
      in studies of the physiology and patho-physiology of the bladder.

PMID- 12525853
TI  - Regulation and co-ordination of nuclear gene expression during mitochondrial
      biogenesis.
AB  - Biogenesis of mitochondria is happening constantly due to the physiological and
      developmental situation of a cell. As mitochondrial biogenesis is a complex
      process producing about 20 % of cellular protein, the expression of the 1000
      genes involved is expected to be coordinated and regulated tightly. The variety
      of physiological stimuli and differentiation states lead to the idea of a complex
      network connecting many different regulatory pathways. By analysing nuclear
      encoded mitochondrial genes some of the factors involved in the regulation and
      coordination of mitochondrial gene expression were identified. These factors
      include general transcription factors such as Sp1 or YY1, as well as
      transcription factors specific for mitochondrial genes like the nuclear
      respiratory factors NRF1 and 2. An important control function linked to the
      physiological situation of a cell is triggered by hormones such as steroid and
      thyroid hormones. Even cell type-specific regulatory proteins like the myogenin
      transcription factor family have a strong influence on some mitochondrial genes
      in the specific cellular background. The regulatory function of most of these
      proteins can be modulated and enhanced by the coactivators PGC-1a and b and PRC.
      Although regulatory pathways have been characterized in more detail in recent
      years, no regulation mechanism has been shown to work on all analysed
      mitochondrial genes, and the general concept of mitochondrial regulation still
      remains unclear.

PMID- 12525854
TI  - Replication and transcription of mammalian mitochondrial DNA.
AB  - Mitochondria are subcellular organelles, devoted mainly to energy production in
      the form of ATP, that contain their own genetic system. Mitochondrial DNA
      codifies a small, but essential number of polypeptides of the oxidative
      phosphorylation system. The mammalian mitochondrial genome is an example of
      extreme economy showing a compact gene organization. The coding sequences for two
      ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and 13 polypeptides are
      contiguous and without introns. The tRNAs are regularly interspersed between the
      rRNA and protein-coding genes, playing a crucial role in RNA maturation from the
      polycistronic transcripts. A single major non-coding region, called the D-loop
      region, contains the main regulatory sequences for transcription and replication
      initiation. This genetic organization has its precise correspondence in the mode
      of expression and distinctive structural features of the RNAs. The basic
      mechanisms of mitochondrial DNA transcription and replication and the main cis
      acting elements playing a role in both processes have been determined. Many trans
      acting factors involved in mitochondrial gene expression, including the RNA and
      DNA polymerases, have been cloned or identified. However, the regulatory
      mechanisms participating in mitochondrial gene expression are still poorly
      understood. The interest to complete this knowledge is increased by the
      involvement of mitochondria in human diseases, in basic processes such as heat
      production, Ca(2+) homeostasis and apoptosis, and by their potential role in
      ageing and carcinogenesis.

PMID- 12525855
TI  - Import of nuclear-encoded proteins into mitochondria.
AB  - The majority of mitochondrial proteins are encoded by nuclear genes, synthesized
      in the cytosol and subsequently imported into mitochondria through protein
      translocation machineries of the outer and inner membranes. In this review, we
      discuss the arrangement of the various translocation complexes and the function
      of individual import components. We also outline the various targeting pathways
      that preproteins can take in order to reach their appropriate sub-mitochondrial
      compartment.

PMID- 12525856
TI  - The 'novel' 'uncoupling' proteins UCP2 and UCP3: what do they really do? Pros and
      cons for suggested functions.
AB  - The scientifically novel, but evolutionarily ancient, so-called uncoupling
      proteins 2 and 3 (UCP2, UCP3) are structurally similar to the archetypical
      uncoupling protein UCP1. A series of suggestions have been forwarded for their
      physiological function. We discuss systematically here the pros and cons for
      these suggestions. We conclude that the novel UCPs do not seem to be
      physiologically relevant uncoupling proteins; the uncoupling property was
      apparently a late introduction into the subfamily through the evolution of UCP1.
      Physiological functions ascribed to UCP2 and UCP3 based on their purported
      uncoupling property may have to be revised (i.e. any type of thermogenesis,
      including protection against obesity, protection against the formation of
      reactive oxygen species and thermogenic involvement in the fever response). The
      presence of a mixed genetic background in most published studies of UCP2 or UCP3
      gene-ablated mice also means that data concerning marked differences in diabetes
      propensity, infection sensitivity and production of reactive oxygen species may
      require confirmation in backcrossed mice. The increased expression of UCP2 and
      UCP3 under conditions of increased fatty acid metabolism implies an as yet
      undefined role in lipid metabolism. Thus, the novel UCPs should probably be
      considered as mitochondrial carriers, and the challenge now is to identify the
      transported molecule.

PMID- 12525857
TI  - Role of mitochondria in apoptosis.
AB  - Apoptosis is an evolutionary-conserved physiological mechanism to remove cells
      from an organism. Cellular apoptosis is mediated via an intracellular signalling
      programme that involves a variety of signalling molecules and cellular organelles
      including caspases, sphingomyelinases, Bcl-2-like proteins and proteins to cleave
      the DNA and mitochondria. Mitochondria contain several pro-apoptotic molecules
      that activate cytosolic proteins to execute apoptosis, block anti-apoptotic
      proteins in the cytosol and directly cleave nuclear DNA. Mitochondria trap these
      pro-apoptotic proteins and physically separate pro-apoptotic proteins from their
      cytoplasmic targets. Apoptosis is then initiated by the release of mitochondrial
      pro-apoptotic proteins into the cytosol. This process seems to be regulated by
      Bcl-2-like proteins and several ion channels, in particular the permeability
      transition pore (PTP) that is activated by almost all pro-apoptotic stimuli.

PMID- 12525858
TI  - The role of mitochondria in cytoplasmic Ca2+ cycling.
AB  - It has been known for a long time that isolated mitochondria are able to
      accumulate large amounts of calcium ions. Before the discovery that endoplasmic
      reticulum (ER) was the main Ca(2+)-storing cellular organelle, mitochondria were
      thought to play a major role in cytoplasmic Ca(2+) homeostasis (Carafoli, 2002).
      After IP(3) was discovered and it was shown that IP(3) receptors were localized
      in ER membrane and that Ca(2+)-binding proteins such as calsequestrin could store
      large amounts of Ca(2+) in the ER, the role of mitochondria in the regulation of
      cytoplasmic Ca(2+) was questioned. However, in recent years, mostly due to the
      development of new methods, there has been increasing evidence that mitochondria
      could be an important cytoplasmic Ca(2+) sink, especially under conditions of a
      high cellular Ca(2+) load.

PMID- 12525859
TI  - Plasticity of skeletal muscle mitochondria in response to contractile activity.
AB  - Regularly performed exercise in the form of endurance training produces a well
      established adaptation in skeletal muscle termed mitochondrial biogenesis. The
      physiological benefit of this is an enhanced performance of muscle when subject
      to endurance exercise. This is not only of great advantage for athletic
      endeavours, but it also clearly improves the quality of life of previously
      sedentary individuals and those involved in injury rehabilitation. Here we review
      the molecular basis for mitochondrial biogenesis in muscle, from the initial
      signals arising in contracting muscle, to the transcription factors involved in
      mitochondrial and nuclear DNA transcription, as well as the post-translational
      import mechanisms required for the synthesis of the organelle. We discuss
      specific protein components associated with reactive oxygen species production,
      and suggest some questions which remain unanswered with respect to the role of
      exercise-induced mitochondrial biogenesis in ageing, apoptosis and disease.

PMID- 12525860
TI  - Response of skeletal muscle mitochondria to hypoxia.
AB  - This review explores the current concepts relating the structural and functional
      modifications of skeletal muscle mitochondria to the molecular mechanisms
      activated when organisms are exposed to a hypoxic environment. In contrast to
      earlier assumptions it is now established that permanent or long-term exposure to
      severe environmental hypoxia decreases the mitochondrial content of muscle
      fibres. Oxidative muscle metabolism is shifted towards a higher reliance on
      carbohydrates as a fuel, and intramyocellular lipid substrate stores are reduced.
      Moreover, in muscle cells of mountaineers returning from the Himalayas, we find
      accumulations of lipofuscin, believed to be a mitochondrial degradation product.
      Low mitochondrial contents are also observed in high-altitude natives such as
      Sherpas. In these subjects high-altitude performance seems to be improved by
      better coupling between ATP demand and supply pathways as well as better
      metabolite homeostasis. The hypoxia-inducible factor 1 (HIF-1) has been
      identified as a master regulator for the expression of genes involved in the
      hypoxia response, such as genes coding for glucose transporters, glycolytic
      enzymes and vascular endothelial growth factor (VEGF). HIF-1 achieves this by
      binding to hypoxia response elements in the promoter regions of these genes,
      whereby the increase of HIF-1 in hypoxia is the consequence of a reduced
      degradation of its dominant subunit HIF-1a. A further mechanism that seems
      implicated in the hypoxia response of muscle mitochondria is related to the
      formation of reactive oxygen species (ROS) in mitochondria during oxidative
      phosphorylation. How exactly ROS interfere with HIF-1a as well as MAP kinase and
      other signalling pathways is debated. The current evidence suggests that
      mitochondria themselves could be important players in oxygen sensing.

PMID- 12525861
TI  - The effects of steroid hormones on the transcription of genes encoding enzymes of
      oxidative phosphorylation.
AB  - Regulation of energy metabolism is one of the major functions of steroid
      hormones. In this process, mitochondria, by way of oxidative phosphorylation,
      play a central role. Depending on the energy needs of the cell, on the tissue, on
      the developmental stage and on the intensity of the hormonal stimulus, the
      response can be an activation of pre-existing respiratory chain components, an
      increased transcription of nuclear-encoded and/or mitochondrial-encoded
      respiratory chain enzyme (OXPHOS) genes and of biosynthesis of the respective
      enzyme subunits or, in extreme cases of high energy needs, an increase in the
      number of mitochondria and mitochondrial DNA content per cell. Some of the
      hormonally regulated systems involving effects on nuclear and mitochondrial
      OXPHOS genes are reviewed in this paper. The possible molecular mechanisms of
      steroid hormone action on nuclear and mitochondrial gene transcription and
      possible ways of coordination of transcription in these two separate cell
      compartments involving direct interaction of steroid receptors with hormone
      response elements in nuclear OXPHOS genes and in mitochondria and
      induction/activation of nuclear-encoded regulatory factors affecting
      mitochondrial gene transcription are presented.

PMID- 12525862
TI  - Cold-induced recruitment of brown adipose tissue thermogenesis.
AB  - Non-shivering thermogenesis in brown adipose tissue is the main mechanism for
      thermoregulatory heat production in small mammals and newborns. During cold
      acclimation the sympathetic innervation triggers the recruitment of brown adipose
      tissue by hyperplasia, which involves the proliferation and differentiation of
      precursor cells, and by hypertrophy of mature brown adipocytes. Mitochondrial
      biogenesis and increased synthesis of the uncoupling protein 1 (UCP-1) are
      hallmarks of the thermogenic recruitment process. The severalfold increase of
      mitochondrial protein content during cold acclimation recruits a large capacity
      for oxidative phosphorylation. However, UCP-1 increases proton leakage across the
      inner membrane of brown adipocyte mitochondria and thereby dissipates proton
      motive force as heat instead of ATP synthesis. During recent years considerable
      progress has been achieved in the analysis of transcriptional mechanisms
      controlling Ucp1 gene expression. However, so far only little is known about the
      molecular basis of cold-induced mitochondrial biogenesis in brown adipose tissue.

PMID- 12525863
TI  - Different metabolic properties of mitochondrial oxidative phosphorylation in
      different cell types--important implications for mitochondrial cytopathies.
AB  - The metabolic and functional diversity of animal mitochondria caused by different
      mitochondrial compositions due to tissue-specific mitochondrial pathways and
      tissue-specific differences in expression of isoforms of subunits of enzymes
      participating in oxidative phosphorylation will be reviewed here. Applying the
      concept of metabolic control analysis, the relevance of this diversity for the
      explanation of tissue-specific effects observed in mitochondrial diseases with
      homoplasmic mitochondrial DNA mutations and nuclear-encoded respiratory chain
      defects is discussed.

PMID- 12525864
TI  - Mitochondrial diseases--an expanding spectrum of disorders and affected genes.
AB  - Mitochondrial diseases are a heterogeneous group of disorders caused by the
      impairment of the mitochondrial oxidative phosphorylation system which have been
      associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear
      gene mutations. The clinical phenotypes are very diverse and the spectrum is
      still expanding. This review gives an overview of the principal clinical
      phenotypes and the molecular genetic basis of mitochondrial disorders identified
      so far.

PMID- 12525865
TI  - Live now--pay by ageing: high performance mitochondrial activity in youth and its
      age-related side effects.
AB  - Radical oxygen species are a byproduct of normal energy metabolism in
      mitochondria. The short-lived radicals cause damage to their immediate
      surrounding, i.e. the mitochondria. While most of this damage will be removed by
      normal mitochondrial turnover, damage to mitochondrial DNA (mtDNA) can persist
      and may accumulate with age. Recent evidence indicates that mutant mtDNA
      molecules can accumulate within individual cells, potentially hampering
      mitochondrial function.

PMID- 12525866
TI  - Possible role of cytoskeleton in intracellular arrangement and regulation of
      mitochondria.
AB  - The origin of significant differences between the apparent affinities of heart
      mitochondrial respiration for exogenous ADP in isolated mitochondria in vitro and
      in permeabilized cardiomyocytes or skinned fibres in situ is critically analysed.
      All experimental data demonstrate the importance of structural factors of
      intracellular arrangement of mitochondria into functional complexes with
      myofibrils and sarcoplasmic reticulum in oxidative muscle cells and the control
      of outer mitochondrial membrane permeability. It has been shown that the high
      apparent K(m) for exogenous ADP (250-350 mM) in permeabilized cells and in ghost
      cells (without myosin) and fibres (diameter 15-20 mm) is independent of intrinsic
      MgATPase activity. However, the K(m) may be decreased significantly by a
      selective proteolytic treatment, which also destroys the regular arrangement of
      mitochondria between sarcomeres and increases the accessibility of endogenous ADP
      to the exogenous pyruvate kinase-phosphoenolpyruvate system. The confocal
      microscopy was used to study the changes in intracellular distribution of
      mitochondria and localization of cytoskeletal proteins, such as desmin, tubulin
      and plectin in permeabilized cardiac cells during short proteolytic treatment.
      The results show the rapid collapse of microtubular and plectin networks but not
      of desmin localization under these conditions. These results point to the
      participation of cytoskeletal proteins in the intracellular organization and
      control of mitochondrial function in the cells in vivo, where mitochondria are
      incorporated into functional complexes with sarcomeres and sarcoplasmic
      reticulum.

PMID- 12525867
TI  - Herpesvirus saimiri: a potential gene delivery vector (review).
AB  - The success of human gene therapy relies on efficient delivery and appropriate
      expression of therapeutic genes which will cure or slow the progression of a
      disease. However, current viral vectors do not possess the full complement of
      properties that are generally believed necessary in an ideal gene delivery
      system. Therefore, alongside attempts to improve current gene delivery vectors,
      the identification and evaluation of new viral vectors is crucial to the long
      term success of gene therapy. Herpesviruses are large DNA viruses which possess a
      number of advantages as gene delivery vectors. These relate to an ability to
      package large DNA insertions and establish lifelong latent infections in which
      the genomic material exists as a stable episome. This review aims to high-light
      an alternative herpesvirus vector system based on Herpesvirus saimiri (HVS), and
      illustrates the properties and development of this potential gene delivery
      vector. HVS is the prototype gamma-2 herpesvirus, or rhadinovirus, originally
      isolated from its natural host, the squirrel monkey. HVS is capable of infecting
      a range of human cell lines with high efficiencies, in particular human carcinoma
      cell lines. Moreover, the HVS viral genome does not integrate into the cellular
      genome and persist as a high copy number, circular, non-integrated episome which
      segregate to progeny upon cell division. This allows the virus to stably
      transduce a dividing cell population and provide sustained transgene expression
      for an extended period of time in both in vitro and in vivo studies. These
      properties merit its continual development as a possible gene delivery vector for
      the future.

PMID- 12525868
TI  - Radiation-induced reactive oxygen species formation prior to oxidative DNA damage
      in human peripheral T cells.
AB  - Previously, we demonstrated that human peripheral T lymphocytes revealed early
      apoptotic changes (annexin V-positive) and late apoptotic changes (propidium
      iodide-positive), at 13 and 24 h, respectively, after irradiation of 5 Gy.
      Changes in mitochondrial membrane potential were observed at 10 h after
      irradiation of 5 Gy. Subsequently, mitochondrial cytochrome c-release was
      confirmed. In order to elucidate the mechanism which acts prior to the
      mitochondrial membrane potential changes, we examined in the previous study the
      radiation dose and the timing of oxidative DNA damage induced in human peripheral
      T lymphocytes following 10 MV X-ray irradiation. As a result, the production of 8
      oxoguanine, i.e., the product of oxidative DNA damage, was clearly identified
      starting at 10, 6, and 3 h, after 2, 5, and 20 Gy of irradiation, respectively.
      Therefore, we examined in the present study reactive oxygen species (ROS)
      formation in T lymphocytes following 5 Gy of irradiation. Using a CCD camera
      system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl
      ester of dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent
      until oxidized by ROS. We found that ROS formation occurred immediately after
      irradiation, continued for several hours, and resulted in oxidative DNA damage.
      Therefore, the origin of hyper-radiosensitivity of T lymphocytes seemed to be the
      high production of ROS in the mitochondrial DNA following irradiation.

PMID- 12525869
TI  - Enhanced expression of endothelin-A receptor in human transplant renal
      arteriosclerosis.
AB  - Transplant renal arteriosclerosis (TRA), characterized by concentric neointimal
      thickening, is one of the major causes of chronic rejection in human kidney
      transplantation. Endothelin-1 is known to be a powerful vasoconstrictor and a
      vascular smooth muscle cell mitogen. Previous experimental studies have shown
      that endothelin-A receptor (ET(A) receptor) is expressed selectively in vascular
      smooth muscle cells, and is the major mediator of endothelin-1-induced effects.
      However, ET(A) receptor expression in human renal allografts has not been
      reported. In this study, we immunohistochemically investigated the expression of
      ET(A) receptor in relation to the development of TRA, using nine human renal
      allografts removed due to rejection and ten normal kidneys as controls. In
      intrarenal arteries of normal kidneys, medial smooth muscle cells showed weak
      expression of ET(A) receptor. In intrarenal arteries with TRA of human renal
      allografts, increased expression of ET(A) receptor was found in medial smooth
      muscle cells, and distinct expression of ET(A) receptor was also detected in
      smooth muscle cells within the neointima. These results suggest that enhanced
      expression of ET(A) receptor may induce an increase in the local proliferative
      and vasoconstrictive effects of endothelin-1 in human renal allografts.

PMID- 12525870
TI  - Adrenomedullin is expressed in cord blood hematopoietic cells and stimulates
      their clonal growth.
AB  - Adrenomedullin (AM) is a hypotensive peptide, which originates from the
      proteolytic cleavage of pro(p)AM and acts via AM22-52-sensitive receptors.
      Reverse transcription polymerase chain reaction allowed the detection of the
      specific mRNAs of pAM in the mononuclear hematopoietic cells of the cord blood
      and immunocytochemistry demonstrated their abundant AM-immunoreactivity. AM (10(
      8) M) markedly enhanced clonal growth of cord blood hematopoietic cells cultured
      on semisolid media added with stem cell-growth promoting cytokines, and this
      effect was abolished by AM22-52 (10(-6) M). Collectively, these findings indicate
      that AM is expressed in and stimulates the proliferation of cord blood
      hematopoietic stem cells. Cord blood has been proposed as a source of stem cells
      alternative to bone marrow for allogeneic transplantation, and our study suggests
      that AM may be used, in addition to the classic cytokines, to expand in vitro
      cord blood stem cells in advance of their clinical use.

PMID- 12525871
TI  - Transforming growth factor-beta released by PPD-presenting malignant mesothelioma
      cells inhibits interferon-gamma synthesis by an anti-PPD CD4+ T-cell clone.
AB  - Besides acting complexly on both normal and tumor cells, transforming growth
      factor-beta (TGF-beta) can determine the nature of the response to the antigen,
      strongly inhibiting the differentiation of naive CD4+ T-cells toward a T helper-1
      (Th-1) phenotype; in a number of experimental models, TGF-beta also appeared to
      be a potent immunosuppressant factor. TGF-beta was shown to be released by some
      human malignant mesothelioma (MMe) cells, which affects the immune response to
      this tumor. Thus, for a better understanding of the role of TGF-beta in the
      immune response to MMe cells, we evaluated the production of a Th-1 cytokine (IFN
      gamma) and of a Th-2 cytokine (IL-4), following Purified Protein Derivative (PPD)
      recall antigen presentation by human MMe cells to a class-II major
      histocompatibility complex (MHC-II)-matched PPD clone (PPD clone). Our data
      confirm that human MMe cells possess the unusual capability of presenting a
      common recall antigen to CD4+ lymphocytes but also show that these tumor cells
      can abrogate Th-1 immune response, as evidenced by a shift in favor of the
      production of IL-4 over that of IFN-gamma, through a TGF-beta-mediated pathway;
      only the simultaneous block of TGF-beta1 and beta2 effects can significantly
      restore a typical Th-1 pattern of cytokine production by PPD clone in response to
      PPD presentation by MMe. Even though the role of TGF-beta in the promotion of MMe
      growth should be further and better defined, this effect should be considered
      when designing new therapeutical approaches aimed at improving the immune
      response to MMe.

PMID- 12525872
TI  - Impaired function of antigen-presenting dendritic cells in patients with chronic
      hepatitis B: localization of HBV DNA and HBV RNA in blood DC by in situ
      hybridization.
AB  - Antigen-presenting dendritic cells (DCs), which play a major role in the
      triggering of primary anti viral immune reactions, may also contribute, in some
      viral models, to the pathogenesis of persistent viral infection. In fact,
      impaired immune response to hepatitis B virus (HBV)-encoded antigens is seen in
      patients with chronic hepatitis B (CH-B). The aim of this study was to check the
      function of DCs in these patients and to investigate the underlying mechanism.
      DCs were enriched from peripheral blood mononuclear cells by culturing with
      interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor for 7
      days. The stimulatory capacity of DCs were checked in allogenic mixed leukocyte
      (MLR) reaction. The levels of IL-12 in the culture supernatants were measured by
      an enzyme-linked immunosorbent assay. HBV DNA and HBV RNA were localized in DCs
      by polymerase chain reaction (PCR) in situ hybridization and reverse
      transcriptase (RT)-PCR in situ hybridization. The stimulatory capacity of DCs in
      allogenic MLR was significantly lower in patients with CH-B (36321+/-12523 cpm,
      n=18) compared to that of normal controls (65678+/-11174 cpm, n=18) (p<0.0001).
      Significantly lower levels of IL-12 were detected in cultures containing DCs from
      patients with CH-B than normal controls (46.7+/-25.6 versus 122.4+/- 37.1 pg/ml,
      p<0.0001). In situ hybridization revealed the localization of HBV DNA and HBV RNA
      in DCs from patients with CH-B. These results indicate that chronic infection by
      HBV is associated with functional defects of DCs. Localization of HBV DNA and HBV
      RNA indicates that DCs may constitute an extra hepatic reservoir and possibly of
      replication of HBV.

PMID- 12525873
TI  - Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time
      quantitative polymerase chain reaction in patients with inflammatory bowel
      disease.
AB  - Although the cytokine network plays a key role in the inflammatory responses in
      inflammatory bowel disease, no comprehensive analysis of the intestinal cytokine
      network has been reported. We analyzed messenger RNA levels for various cytokines
      in human intestine by real-time quantitative polymerase chain reaction to clarify
      the cytokine profiles involved in the pathogenesis of inflammatory bowel disease.
      Biopsy specimens were obtained from 23 patients with ulcerative colitis (15 men,
      8 women, mean age of 44.1 years), 17 patients with Crohn's disease (15 men, 2
      women, mean age of 21.6 years), and 8 normal controls (6 men, 2 women, mean age
      of 62.7 years) who underwent colonoscopy for suspected colonic disease. Messenger
      RNA was isolated from two biopsy samples and reverse-transcribed to obtain cDNA.
      Mucosal mRNA levels for IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL
      12p40, IL-15, IFN-gamma and TNF-alpha were simultaneously analyzed by real-time
      quantitative polymerase chain reaction. In patients with active ulcerative
      colitis, IL-1beta, IL-4, IL-5, IL-8, IL-12p40, IFN-gamma and TNF-alpha mRNA
      levels were significantly higher than those in controls. In patients with active
      Crohn's disease, IL-1beta, IL-8, and IL-12p40 mRNA levels were significantly
      higher than those in controls. Mucosal level of IL-12p40 mRNA was significantly
      higher in patients with inactive Crohn's disease than in controls. Both Th1 and
      Th2 cytokine mRNA levels were increased in colonic mucosa of patients with
      ulcerative colitis suggesting the possibility that cellular and humoral immunity
      play roles in the pathogenesis of this disease. In patients with Crohn's disease,
      Th1 cytokine mRNA levels were increased in colonic mucosa, suggesting
      predominance of cellular immunity in the pathogenesis of this disease.

PMID- 12525874
TI  - CaMKIV expression is associated with clinical stage and PCNA-labeling index in
      endometrial carcinoma.
AB  - Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a multifunctional protein
      kinase expressed abundantly in the central nervous system. Because changes in
      intracellular Ca2+ concentrations affect progression through the mitotic cell
      cycle, enhanced expression of CaMKIV has been reported in small cell lung
      carcinoma and hepatocellular carcinoma. To elucidate the involvement of CaMKIV in
      endometrial carcinogenesis, we analyzed serial frozen sections from 31 patients
      with endometrial carcinoma and 20 patients with normal endometria for CaMKIV
      protein expression, using fluorescent immunohistochemistry. We analyzed the
      relationship between the percentages of CaMKIV stained cells and the patient
      characteristics, including clinical stage, histological grade, myometrial
      invasion, and clinical outcome. In the normal endometria, CaMKIV was detected in
      none of the cases examined. Most of the CaMKIV proteins were found in the nucleus
      of endometrial carcinoma tissue. CaMKIV expression was significantly associated
      with clinical stage (stage I and II versus stage III and IV; p<0.01), myometrial
      invasion (no myometrial invasion versus the presence of invasion to greater than
      one-half the myometrium; p=0.02), and clinical outcome (no evidence of disease
      versus died of disease; p=0.04). Scoring on the basis of the percentage of
      positive cells indicated that CaMKIV expression was significantly associated with
      PCNA-labeling index (p=0.02). Our results demonstrate that CaMKIV expression in
      endometrial carcinoma correlates with the malignant potential of this tumor.

PMID- 12525875
TI  - A family of episodic ataxia type 2: no evidence of genetic linkage to the CACNA1A
      gene.
AB  - Episodic ataxia type 2 (EA2) has been reported to result from mutations in the
      CACNA1A gene, located on chromosome 19p13. We describe a family with episodic
      ataxia, clinically indistinguishable from EA2, that was not caused by CACNA1A
      gene mutation. The proband is an 11-year-old boy, who has had 6 cerebellar ataxic
      attacks since 8 years of age. His attacks occurred almost monthly, lasting for 2
      to 3 days. He was treated successfully with acetazolamide. His identical twin,
      mother and grandmother developed ataxic attacks at age 10, 34, and 50,
      respectively. The symptoms in his grandmother improved gradually without
      medication. His mother and identical twin took acetazolamide with a good
      response. We examined the CACNA1A gene for this family but did not detect any
      mutations. Furthermore, there was no evidence of genetic linkage between the
      CACNA1A gene and the symptomatic patients in this family. This suggests that the
      cause of EA2 can be heterogeneous, that is, defects of genes other than CACNA1A
      might be the cause of EA2.

PMID- 12525876
TI  - Synergistic anticancer action of reversibly and irreversibly acting ligands of
      poly (ADP-ribose) polymerase.
AB  - The synergistic interaction of two ligands (INH2BP and the prodrug INO2BA) of
      PARP I has been demonstrated for two human leukemia cell lines (855-2 and HL-60),
      for a human lung cancer cell (A549) and for Eras 20 cancer cells. Synergism was
      calculated using kinetic combination constants based on cell multiplication
      rates. Reducing cellular GSH content by BSO strongly augmented synergism, an
      effect partly explained by the removal of C-NO scavenging (by GSH). However,
      INH2BP action was augmented by BSO, an effect most probably explained by the
      sensitization of the cell to apoptosis by GSH removal.

PMID- 12525877
TI  - Investigation of endotoxin adsorption with polyether polymer alloy dialysis
      membranes.
AB  - Endotoxin (ET) in the dialysate is known to be adsorbed by dialysis membranes
      made of polyether polymer alloy (PEPA) and polymethylmethacrylate (PMMA). In the
      present study, the effect of polyvinylpyrrolidone (PVP) localization of the PEPA
      dialysis membrane on the adsorption of ET was investigated. The compounding of
      PVP in the PEPA membrane was changed, and hydrophobic membrane in both blood side
      and dialysate side, and hydrophilic membrane in only the blood side were used.
      Adsorption was evaluated by filling the contaminated dialysate inside and outside
      the membrane after priming with physiological saline, and determining the ET
      concentration in the blood side and dialysate side of dialysis membrane during
      the 240 min period from the start of filling the contaminated dialysate. With the
      PEPA membranes investigated, ET was significantly adsorbed to the hydrophobic
      side and was not adsorbed to the blood side of hydrophilic type membrane. These
      results suggest that in addition to electrostatic action attributable to the
      compounding of hydrophilic agent PVP to the dialysis membrane, the distribution
      of PVP that was compounded and the potential of the membrane itself may cause
      differences in adsorption of ET.

PMID- 12525878
TI  - Light and electron microscopic analyses of immediate and late tissue damage
      caused by radiofrequency ablation in porcine liver.
AB  - Radiofrequency ablation (RFA) is an effective procedure for localized
      hepatocellular carcinoma. Contrast-enhanced CT depicts the ablated area as a
      hypoattenuated area without hepatic blood flow; however, light microscopy does
      not show obvious necrosis in the ablated area. We evaluated liver tissue changes
      after RFA by light microscopy and electron microscopy. The normal livers of three
      anesthetized pigs were coagulated using RFA after laparotomy. The liver was
      examined immediately, and 1 week after operation by light and electron
      microscopy. After RFA, the liver parenchyma surrounding the needle electrode was
      brown in color and surrounded by a red marginal zone separate from the normal
      liver parenchyma. Hematoxylin-eosin staining of the central area did not show
      cell necrosis, and the structures of liver sinusoids, liver cell cord and the
      nuclei of hepatocytes were preserved. However, electron microscopic examination
      of tissue immediately after RFA showed destruction of mitochondria of hepatocytes
      and fixation of sinusoidal cells. One week later, there was a large quantity of
      debris in the enlarged sinusoids, in addition to irreversible destruction of
      hepatocyte organelles. RFA of the porcine liver causes hepatocyte damage. This
      damage was not evident by light microscopy but clearly identified by electron
      microscopy.

PMID- 12525879
TI  - Suppressive effect of endogenous regucalcin on protein tyrosine phosphatase
      activity in the nucleus of rat brain: attenuation with increasing age.
AB  - The effect of endogenous regucalcin, which is a regulatory protein of Ca2+
      signaling, on protein tyrosine phosphatase activity in the nucleus of brain
      tissues of young and aged rats was investigated. Phosphotyrosine was used as the
      substrate for assay of protein tyrosine phosphatase activity. Protein tyrosine
      phosphatase activity in the brain nucleus of young (5 weeks old) rats was
      significantly increased in the presence of calcium chloride (5-50 micro M) in the
      enzyme reaction mixture. The increase was completely blocked by the addition of
      trifluoperazine (10-50 micro M), an antagonist of calmodulin, indicating that the
      enzyme is activated by endogenous Ca2+/ calmodulin. The addition of regucalcin
      (10(-4)-10(-8) M) in the enzyme reaction mixture caused a significant decrease in
      protein tyrosine phosphatase activity in the absence or presence of calcium
      chloride (20 micro M). Brain nuclear protein tyrosine phosphatase activity was
      significantly raised in the presence of anti-regucalcin monoclonal antibody (10
      50 ng/ml) in the enzyme reaction mixture. The increase was completely prevented
      by the addition of regucalcin (10(-6) M). In the brain nucleus of aged (50 weeks
      old) rats, protein tyrosine phosphatase activity was elevated significantly as
      compared with that of 5 weeks old rats. The effect of anti-regucalcin monoclonal
      antibody in increasing the enzyme activity in the brain nucleus of aged rats was
      seen in the presence of 50 ng/ml of the antibody. Such an effect was not found by
      the antibody of 10 and 25 ng/ml. Regucalcin protein in brain nucleus was detected
      by Western blot analysis. This level was significantly decreased by increasing
      age. The present study demonstrates that endogenous regucalcin plays a
      suppressive role in the regulation of protein tyrosine phosphatase activity in
      the nucleus of rat brain, and that this regulation is attenuated with increasing
      age.

PMID- 12525880
TI  - Study on autologous blood transfusion in hemodialysis patients.
AB  - The storage period of autologous blood of hemodialysis (HD) patients was
      investigated with focus on the red blood cell life span. Healthy subjects, HD
      patients administered recombinant human erythropoietin (rHuEPO) preparation at
      4,500 units/week and at 9,000 units/week were classified into 3 groups,
      respectively. Blood cell system and biochemical parameters were investigated at
      the time of collection (week 0), and weeks 1, 2 and 3 (after 21 days) in the
      storage. There was no significant difference in serum potassium and total
      bilirubin between the groups. Compared with the status in week 0, erythrocyte
      creatine significantly increased in weeks 2 and 3 in the normal group and EPO
      4,500 group. And a significant increase in this parameter was noted in the weeks
      1 and 2 in the EPO 9,000 group. Furthermore, the value demonstrated by the EPO
      4,500 group was significantly higher than that in the normal group at each time
      point. Compared with the normal group, the value was significantly higher in week
      1 in the EPO 9,000 group. However, there was no significant difference between
      the EPO 4,500 and EPO 9,000 groups. Concerning the transfusion of autologous
      blood in HD patients, the degree of hemolysis was smaller than that in the normal
      group. However, in view of the life span of erythrocyte creatine obtained, the
      duration that is shorter than that in the normal group in the first place is
      expected to be further curtailed during the storage period. It is assumed that
      the generally accepted storage period of 21-35 days in the case of autologous
      blood is not applicable in the case of HD patients.

PMID- 12525881
TI  - Detection of cancer cells in the peripheral blood of gastric cancer patients.
AB  - The existence of occult metastasis in peripheral blood has been reported in
      various tumors. However, in gastric cancer (GC), this metastasis has not been
      well analyzed. In the present study, to identify circulating cancer cells in
      patients with GC, peripheral blood samples from GC patients were investigated.
      Total RNA was extracted from 1.5 ml peripheral blood from 55 patients with GC,
      from 34 non-cancer patients, and from 10 healthy volunteers. Carcinoembryonic
      antigen (CEA), cytokeratin 19 (CK19), and 20 (CK20) messenger RNA (mRNA) were
      used as probes to detect GC cells in the blood samples using real-time reverse
      transcriptase polymerase chain reaction (RT-PCR). CEA and CK19 mRNA expression
      were not detected in the 40 healthy volunteers and non-cancer patients, while 2
      of the 40 showed CK20 mRNA expression. In 55 patients with GC, CK19 mRNA was not
      detected and CEA mRNA was detected in only one case (1.8%) with stage IV. While
      CK20 mRNA expression was observed in 15 cases (27.3%) and even in stage I, 8 of
      24 (33.3%) showed CK20 mRNA expression. Thus, the specificity of CK20 marker may
      be low. Even though the sensitivity of CEA marker is low, CEA may be a more
      reliable marker than cytokeratins for detection of cancer cells in GC patient's
      peripheral blood.

PMID- 12525882
TI  - Great increase in bone 66 kDa protein and osteocalcin at later stages with
      healing rat fractures: effect of zinc treatment.
AB  - Fracture healing has been demonstrated to increase production of bone growth
      factors, and this elevation has been shown to be enhanced by zinc treatment.
      Moreover, the effect of zinc treatment on production of bone osteocalcin, which
      is a kind of Ca2+-binding protein localized in bone matrix, at the later stages
      with bone fracture was investigated. Rats were sacrificed 7 (earlier stage) or 21
      (later stage) days after fracture of femoral diaphysis. Femoral-diaphyseal
      tissues with fracture healing were cultured in a serum-free medium for 24 h. Many
      proteins in the bone tissues were released into the medium. Bone protein
      production was markedly elevated 21 days after bone fracture as compared with
      that of 7 days. A approximately 66 kDa protein molecule, a major protein
      component which was produced by the diaphyseal tissues during fracture healing,
      was predominantly increased at the later stages with fracture healing. Bone
      osteocalcin production was significantly increased during fracture healing. This
      increase was enhanced at the later stages with fracture healing. The presence of
      zinc acexamate (10(-4) M) in culture medium caused a significant increase in bone
      protein and osteocalcin production at 7 or 21 days after bone fracture. The
      effect of zinc acexamate in increasing bone total protein and osteocalcin
      production was remarkable at the later stages with fracture healing. Moreover,
      zinc treatment caused a significant increase in alkaline phosphatase activity,
      deoxyribonucleic acid (DNA) and calcium content in the femoral-diaphyseal tissues
      of the later stages with fracture healing in vitro. The present study
      demonstrates that bone protein production is markedly increased at the later
      stages with fracture healing, and that zinc treatment can enhance production of
      bone protein components including osteocalcin in vitro. Zinc treatment may
      stimulate the healing of femoral fracture at earlier and later stages.

PMID- 12525883
TI  - Synchronous activation of ERK 1/2, p38mapk and PKB/Akt signaling by H2O2 in
      vascular smooth muscle cells: potential involvement in vascular disease (review).
AB  - Oxidative stress has been implicated in the pathogenesis of a host of vascular
      abnormalities such as atherosclerosis, hypertension and in restenosis followed by
      balloon angioplasty. However, the molecular mechanism by which oxidative stress
      causes these abnormalities remains poorly characterized. Recent studies have
      shown that exposure of vascular smooth muscle cells (VSMC) with H2O2, to mimic
      oxidative stress, activates components of growth promoting and proliferative
      signal transduction pathways. These components include mitogen-activated protein
      kinases (MAPKs) and protein kinase B (PKB/Akt), and are believed to be key
      players mediating growth, proliferation, hypertrophy, migration, survival and
      death of VSMC. We provide a brief overview of the effect of H2O2 on MAPKs and
      PKB/Akt signaling in VSMC in relation to their potential role in the pathogenesis
      of vascular diseases.

PMID- 12525884
TI  - Association of an interleukin-1beta gene polymorphism at position -511 with
      Alzheimer's disease.
AB  - Inflammation is thought to promote neuronal cell death in Alzheimer's disease
      (AD). The proinflammatory interleukin-1 is a main component in inflammatory
      pathways and is overexpressed in the brain of AD patients. Investigation of
      different polymorphisms in the interleukin-1 genes (IL-1alpha -889, IL-1beta 
      511, IL-1beta +3953) revealed associations between specific alleles and AD in
      that they increased the risk or modified the age at onset of AD. However, there
      are controversial findings from other studies which revealed no significant
      associations between these polymorphisms and AD; thus further evaluation of the
      association of IL-1 gene polymorphisms with AD and their role in pathogenesis is
      needed. In this study we examined the distribution of the IL-1beta -511 alleles
      in AD patients and a control sample of healthy individuals. An additional control
      population of non-demented depressive inpatients was recruited to exclude a
      confounding bias. The cerebrospinal fluid (CSF) levels of Abeta42 in AD patients
      were investigated to assess the influence of IL-1beta -511 genotypes. We found no
      significant association of the IL-1beta -511 polymorphism with AD, suggesting
      that the IL-1beta -511 polymorphism is no risk factor for AD. However, we found
      the Abeta42 CSF levels to be lower in carriers of the IL-1beta CC-genotype
      compared to carriers of the T-allele. Even though IL-1beta -511 polymorphism did
      not influence the risk of AD it might have a pathophysiological influence on the
      disease process.

PMID- 12525885
TI  - Mutational analysis of IkappaBalpha in hematologic malignancies.
AB  - The activation of the NF-kappaB family of transcription factors plays a crucial
      role in oncogenesis. The IkappaB family has the ability to retain the NF-kappaB
      in an inactive complex in the cytoplasm. Recently, mutations of the IkappaBalpha
      gene were found in Hodgkin's lymphoma, which allows NF-kappaB proteins to
      translocate into the nucleus in an active form. In this report, we describe a
      mutational analysis of IkappaBalpha for primary tumor cells obtained from
      patients with a variety of hematologic malignancies (acute myelogenous leukemia,
      chronic myelogenous leukemia, myelodysplastic syndrome, hairy cell leukemia,
      adult T-cell leukemia, and mantle cell lymphoma) as well as 15 leukemia,
      lymphoma, and myeloma cell lines (HL60, U937, HEL, K562, NALM1, Jurkat, JM,
      MOLT4, Raji, KS1, OKM2T, OKM3T, F6T, Su9T01, and C2-2). RT-PCR, followed by
      direct sequencing, was performed and all samples expressed IkappaBalpha. One
      missense mutation was identified in a primary effusion lymphoma cell line, KS1.
      However, NF-kappaB (p65) protein was absent from the nucleus of KS1
      immunohistochemically, suggesting that the mutation did not alter the function of
      IkappaBalpha in this case. Taken together, although it is not clear whether
      normal IkappaBalpha protein was expressed in hematologic malignancies, mutations
      of IkappaBalpha could be rare events in these diseases, except for Hodgkin's
      lymphoma. Alterations of other members of NF-kappaB/ IkappaB family proteins
      might act on the development of hematologic malignancies.

PMID- 12525886
TI  - Cloning and characterization of a novel gene EC97 associated with human
      esophageal squamous cell carcinoma.
AB  - We report on the cloning and characterization of a novel gene EC97 which is
      associated with human esophageal squamous cell carcinoma (ESCC). A fragment of
      expressed sequence tag (EST) (aa700351) was overexpressed in ESCC tissues
      compared with the normal tissues in cDNA microarray data. Based on the sequence
      of aa700351, the full-length cDNA was acquired by polymerase chain reaction (PCR)
      amplification and named EC97. EC97 was 3353 bp long and its encoding protein
      contained 813 amino acid residues. Northern blot and reverse transcription
      polymerase chain reaction (RT-PCR) analysis revealed that EC97 had a transcript
      of 3.4 kb in most human normal tissues we checked and its expression level was
      increased in 60% (12/20) of tested ESCC tissues versus the normal counterparts.
      EC97 was mapped to human chromosome 16p12-16p13.1 using radiation hybridization
      (RH) and predicted to include 25 exons and disseminated over 100 kb of genomic
      DNA.

PMID- 12525887
TI  - Identification and characterization of human PRICKLE1 and PRICKLE2 genes as well
      as mouse Prickle1 and Prickle2 genes homologous to Drosophila tissue polarity
      gene prickle.
AB  - Drosophila prickle is implicated in tissue polarity or planar polarity. Here,
      human PRICKLE1 gene corresponding to FLJ31937 cDNA and human PRICKLE2 gene
      corresponding to DKFZp686D143 cDNA were identified to be homologous to Drosophila
      prickle gene by using bioinformatics. PRICKLE1 gene was mapped to human
      chromosome 12p11-q12, and PRICKLE2 gene was mapped to human chromosome 3p14.
      Mouse Prickle1 and Prickle2 genes were next identified in mouse genome draft
      sequences NW_000106.1 and NW_000262.1, respectively. Human PRICKLE1, PRICKLE2,
      Xenopus Prickle, and Drosophila prickle were homologous in the PET domain, three
      LIM domains, and the C-terminal Prickle homologous (PKH) domain. LMO6 and TESTIN,
      containing the PET domain and three LIM domains, were found to lack the PKH
      domain. Therefore, PRICKLE1 and PRICKLE2 rather than LMO6 and TESTIN were found
      to be human homologs of Drosophila prickle. PRICKLE1 and PRICKLE2 mRNAs were
      expressed together in brain, eye and testis. PRICKLE1 mRNA was expressed in fetal
      heart and hematological malignancies, while PRICKLE2 mRNA in fetal brain, adult
      cartilage, pancreatic islet, gastric cancer with signet-ring cell features, and
      uterus tumors. Because tissue polarity genes frizzled, dishevelled, flamingo, and
      Vang are evolutionary and functionary conserved from Drosophila to human,
      PRICKLE1 and PRICKLE2 might be implicated in the localization of Frizzled and
      Dishevelled proteins, just like Drosophila prickle. This is the first report on
      identification and characterization of human PRICKLE1, PRICKLE2, mouse Prickle1,
      and Prickle2 genes.

PMID- 12525888
TI  - Cloning and characterization of a novel splice variant of the brain-specific
      protein densin-180.
AB  - Densin-180 is a brain-specific synaptic protein of the o-sialoglycoprotein
      family. It functions in specific adhesion between presynaptic and postsynaptic
      membranes at glutamatergic synapses. We have cloned a novel splice variant of
      densin-180 from a fetal brain cDNA library and termed it LRRC7. It is located on
      1p31 and consists of 8 exons. It encodes a putative protein of 216 amino acids
      which contains a nuclear localization signal and four leucine-rich repeats
      (LRRs). LRRs are 20-29 residue sequence motifs present in a number of proteins
      with diverse functions. Expression analysis of LRRC7 shows it is expressed
      ubiquitously while its splice variant densin-180 is brain-specific.

PMID- 12525889
TI  - Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of
      hepatocarcinoma cells.
AB  - Ion movements are among the early signals that could play important roles in
      cancer cell proliferation and metastasis. In this work, we investigated the role
      of K+ channels in adhesion and proliferation of H35 hepatocarcinoma cells. A
      variety of K+ channel blockers were used in order to differentiate the critical
      subtype(s) of K+ channels involved. 4-Aminopyridine, an inhibitor of voltage
      gated K+ channels, significantly reduced the attachment of H35 cells to primary
      rat endothelial layer as determined by CFSE (5-(6-)-carboxyfluorescein diacetate
      succinimidyl ester) fluorescence assay. 4-Aminopyridine also inhibited the
      proliferation of H35 cells as measured by [3H]-thymidine incorporation. Non
      selective K+ channel blockers TPeA and verapamil had similar inhibitory effects
      on H35 cell adhesion and proliferation. In contrast, iberiotoxin, a selective
      inhibitor of KCa channels, had no effect on the adhesion and proliferation of H35
      cells. Glibenclamide, a potent inhibitor of KATP channels, could inhibit the cell
      adhesion and proliferation only at a very high concentration (100 micro M) that
      may block Kv channels. These experiments suggest that Kv channels play an
      important role in the metastasis and proliferation of hepatocarcinoma cells.
      Since inhibition of K+ channels would reduce Ca2+ influx in these cells, it is
      likely that the influence of Kv channels on H35 cell adhesion and proliferation
      is mediated by a Ca2+-dependent mechanism.

PMID- 12525890
TI  - The impact of risk factors of Alzheimer's disease in the Down syndrome.
AB  - Down syndrome (DS) patients, after the fourth decade of life, display some
      neurophatological features of the Alzheimer's disease (AD). Several hypotheses
      suggested that apoE4 protein, an AD risk factor, might promote amyloid formation
      by stabilizing an aggregated conformation of the beta amyloid protein (Abeta).
      This peptide is the major proteinaceous component of the senile plaques either in
      AD or DS, and it is a proteolytic product of the amyloid precursor protein (APP).
      Both brain and platelets express three APP transcripts of the apparent molecular
      weight of 106, 110 and 130 kDa. In DS the Abeta deposits may ensue, at least in
      part, from the overexpression of the Abeta precursor gene located on chromosome
      21. Aims of the present study were to evaluate the frequency of apoE4 isoform in
      DS population, and to ascertain whether the ratio between the 130 and the 106-110
      kDa platelet APP isoforms is lower in DS, as seems to occur in AD patients. ApoE4
      frequency was significantly lower in DS when compared to AD patients. E4 allele
      frequency of older DS patients was about half that of younger ones. The 130 to
      106-110 kDa APP isoform ratio was similar in young DS and control subjects, and
      markedly lower in AD patients. Our results indicate that: i) in DS patients the
      early, selective accumulation of Abeta peptides is independent of the ApoE
      genotype, but the allele epsilon4 predisposes to various causes of premature
      death; and ii) platelet APP isoform abnormalities, which can be observed in AD
      patients, do not occur in young DS patients, suggesting a different processing of
      APP platelets in DS with respect to AD.

PMID- 12525891
TI  - Cat scratch disease in Japan.

PMID- 12525892
TI  - Vaginal bacterial flora of pregnant women colonized with group B streptococcus.
AB  - To elucidate the characteristics of group B streptococcus (GBS)-positive vaginal
      flora in pregnant women, vaginal cultures were conducted in 4025 women at 22 to
      36 weeks of gestation. The results were analyzed by Fisher's exact test. Among
      4025 women, 408 were found to be GBS positive and 3617 were GBS negative (GBS
      negative group). A total of 1151 bacterial strains were recovered in the GBS
      positive group and 6746 strains in the GBS-negative group. The percentages of
      Gram-positive cocci other than GBS, anaerobes, fungi, and Lactobacillus were
      18.8%, 1.4%, 6.0%, and 34.4%, respectively, in the GBS-positive group, and 30.4%,
      4.1%, 8.8%, and 53.5% in the GBS-negative group. The percentages were
      significantly lower in the GBS-positive group ( P < 0.0001, P < 0.0001, P=
      0.0012, P < 0.0001, respectively). Judging from the reduction in Lactobacillus,
      the GBS-positive vaginal flora is not considered a normal flora. However, it is
      not regarded as a pathogenic flora either, because the isolation rates of
      anaerobes (strongly associated with bacterial vaginosis) and fungi (occasionally
      causing vulvovaginal candidiasis) were lower than in the GBS-negative flora.
      These results suggest that the GBS-positive flora is associated with a lower risk
      of abnormality during pregnancy and abnormal pregnancy outcome compared with the
      GBS-negative flora, although this group is one of the most important pathogens in
      neonatal infections.

PMID- 12525893
TI  - Experimental tinea unguium model to assess topical antifungal agents using the
      infected human nail with dermatophyte in vitro.
AB  - Therapy for onychomycosis is difficult because a complete cure requires long-term
      treatment. Although strong systemic antifungal drugs are potent enough to achieve
      a cure, they often have side effects. Therefore, one approach is to develop a new
      topical antifungal drug to act directly on the nail tissue. In this study, we
      developed a new in vitro model for assessing antifungal activity using the human
      nail. An O-ring was fixed with silicon bond to the dorsal surface of the nail. An
      antifungal agent applied to the surface will penetrate the nail tissue. The
      ventral side of the nail was placed on an agar plate inoculated with conidia of
      Trichophyton mentagrophytes. Nail specimens were infected with the fungi from the
      agar, and a clear fungal colony formed on the agar surrounding the nail on the
      fifth day of cultivation. After 14 days, the fungal colony in the control groups
      was shown to be expanding over the entire nail. The fungal colony in the group
      treated with sodium pyrithione had disappeared. Although the in vitro antifungal
      activity of sodium pyrithione has poor potency among the agents used, it showed
      remarkable antifungal activity, as assessed by image analysis. This model enables
      one to evaluate the activity of a topical antifungal agent that has penetrated
      human nail tissue, and it may facilitate research on a topical agent for
      onychomycosis.

PMID- 12525894
TI  - Staphylococcus aureus isolated from hospital staff: a comparative study of Laos
      and Japan.
AB  - Staphylococcus aureus isolated from hospital staff (nurses and doctors) in Laos
      were characterized for future reference and for comparison with organisms found
      in Okinawa, Japan. No methicillin-resistant S. aureus (MRSA), among 38 isolates
      examined, was found in Laos, but 16 of 36 Japanese isolates (44%) were identified
      as MRSA. The minimum inhibitory concentrations (MICs) of ampicillin and
      tetracycline against Lao isolates were definitely higher than those against
      Japanese isolates. The MIC(80) of tetracycline was 50 microg/ml and 0.4 microg/ml
      in Lao and Japanese isolates, respectively. There was no marked difference in the
      production of enterotoxin by S. aureus strains in the two countries. Toxic shock
      syndrome toxin-1 was produced by only 1 of 38 Lao isolates but by 5 of 36
      Japanese isolates. Coagulase types varied greatly, but about 50% of the isolates
      in both countries produced untypable coagulase. Since the interaction of Laotians
      with foreigners has increased rapidly in recent years, the careful monitoring of
      drug-resistant pathogens is required.

PMID- 12525895
TI  - Antimicrobial resistance and DNA-fingerprinting pattern of Burkholderia cepacia
      blood isolates.
AB  - The minimum inhibitory concentrations (MICs) of six antibiotics against 33
      strains of Burkholderia cepacia isolated from 33 patients suspected of having
      sepsis or bacteremia were determined. All the B. cepacia isolates were resistant
      to gentamicin (MIC(90), >128 microg/ml), and 21.2% were resistant to imipenem
      (MIC(90), 16 microg/ml). They were susceptible to ciprofloxacin, ceftazidime, and
      minocycline (MIC(90), 2-8 microg/ml). The 33 blood isolates were classified into
      12 types (A-L) by the pulsed-field gel electrophoresis pattern. All 11 of A type,
      2/4 of B type, 3/4 of C type, 4/5 of E type, and both G type B. cepacia were
      isolated from different patients in the same hospital. These results suggest that
      B. cepacia can spread among patients with sepsis or bacteremia.

PMID- 12525896
TI  - Enteroaggregative Escherichia coli: incidence in Japan and usefulness of the
      clump-formation test.
AB  - The usefulness of the clump-formation test described by Albert et al. for
      identifying enteroaggregative Escherichia coli (EAggEC) and the incidence of
      EAggEC in Japan were studied. One hundred and seventy strains of E. coli
      agglutinated with enteropathogenic E. coli diagnostic antisera were collected
      from a variety of districts in Japan. All isolates were from diarrheal stools.
      EAggEC was identified on the basis of the presence of the aggR gene accompanied
      by aggregative adhesion to HEp-2 cells. After 24 strains carrying eaeA, elt, est,
      stx-1, stx-2, or ipaH genes were eliminated, the remaining 145 strains were
      examined for adhesion to Hep-2 cells, the presence of the aggRgene, and clump
      formation on the surface of Muller-Hinton broth. aggR was detected in 10 strains,
      and 9 of them displayed aggregative adhesion to HEp-2 cells. Seven strains
      produced marked clumps and 22 showed moderate clump formation. The sensitivity
      and specificity of the clump-formation test for detecting EAggEC were each about
      90%, and they varied slightly depending on the stringency of evaluation for the
      degree of clump formation. From these results, we conclude that the incidence of
      EAggEC cannot be ignored as a possible cause of diarrheal disease in Japan, and
      we strongly recommend the clump-formation test for detecting EAggEC.

PMID- 12525898
TI  - Evaluation of antibacterial efficacy of drugs for urinary tract infections by
      genotyping based on pulsed-field gel electrophoresis (PFGE).
AB  - We attempted to determine whether the same bacterium isolated from patients with
      urinary tract infections (UTI) before and after treatment with antimicrobial
      agents was of the same strain ("persisted") or of a different strain ("changed").
      Furthermore, to verify the effectiveness of antimicrobial agents for UTI, we
      investigated whether bacterial strains could be classified as persisted or
      changed based on their electrophoretic patterns in pulsed-field gel
      electrophoresis (PFGE). We examined eight species of bacteria ( Enterococcus
      avium, Staphylococcus epidermidis, Pseudomonas fluorescens, Serratia marcescens,
      Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, and
      Escherichia coli), consisting of 41 strains (19 pairs isolated before and after
      treatment with antimicrobial agents) isolated from patients with complicated UTI.
      It was concluded that all bacteria were unchanged, based on the clinical effect
      on bacteriuria. The chromosomal DNA of these bacteria was digested with
      restriction enzymes and classified based on their electrophoretic pattern in
      PFGE. A comparison of the patterns of the fragments revealed that 14 pairs were
      indistinguishable before and after treatment, 3 pairs were closely related, 1
      pair was possibly related, and 1 pair was different. These results demonstrated
      that 18 pairs of isolates (indistinguishable, closely related, and possibly
      related) were highly likely to be continued infections by the same strain, and
      that 1 pair (different) had been replaced by another strain. Based on these
      results, we believe that bacterium genotyping by PFGE is a more effective method
      for evaluating the antibacterial efficacy of antimicrobial agents.

PMID- 12525897
TI  - Cat scratch disease: analysis of 130 seropositive cases.
AB  - To clarify the clinical manifestations of cat scratch disease (CSD), we evaluated
      a total of 130 seropositive patients with CSD. The patients' ages ranged from 1
      to 68 years; 103 (79.2%) were under 18 years of age. CSD occurred predominantly
      in the fall and winter months. Regional lymphadenopathy was noted in 110 (84.6%)
      of the cases, and the most common sites were the neck (33%), axillary (27%), and
      inguinal (18%) regions. One hundred of the patients (77%) had general symptoms,
      such as fever, headache, and malaise. The clinical manifestations of CSD showed a
      wide spectrum from typical or classical CSD, with regional lymphadenopathy, to
      atypical or systemic CSD. Of the 130 cases, 103 (79.2%) were typical CSD and 27
      (20.8%) were atypical CSD. Atypical cases of CSD were commonly reported as fever
      of unknown origin (37.0%), neuroretinitis (22.2%), encephalopathy (14.8%),
      hepatosplenic granuloma (11.1%), and Parinaud's oculoglandular syndrome (7.4%).
      Fever of unknown origin or prolonged fever lasting more than 14 days was evident
      in 27 (20.8%) of the 130 cases in this study. Eleven of the 27 cases lacked
      lymphadenopathy. Our findings suggest that CSD is not a rare disease in Japan.
      The indirect fluorescent antibody (IFA) test to detect Bartonella species may
      provide a prompt diagnosis of CSD and facilitate appropriate therapy.

PMID- 12525899
TI  - The first isolation of Nocardia nova from an HIV-1 infected individual in Japan.
AB  - Nocardia species are opportunistic pathogens of immunocompromised patients. We
      report a case of Nocardia nova infection complicating Pneumocystis carinii
      pneumonia (PCP) in an HIV-1 infected individual. A 27-year-old man with
      hemophilia A was admitted on October 17, 2000, with fever and dyspnea. CD4 cell
      counts were 5/microl on admission. Prophylaxis against PCP was administered by
      inhalation of pentamidine isethionate because he was allergic to sulfamethoxazole
      trimethoprim (SMZ-TMP). He was diagnosed with PCP from chest X-ray and
      bronchoalveolar lavage. The sputum obtained for culture on admission was positive
      for Gram-positive branching rods; the organism was later identified as Nocardia
      nova. He died from respiratory failure on November 7, 2000. Although PCP might be
      a principal factor in respiratory failure, this case shows the need to consider
      pulmonary nocardiosis as a cause of respiratory illness in patients with advanced
      HIV-1 infection.

PMID- 12525900
TI  - A patient with primary human immunodeficiency virus infection for whom highly
      active antiretroviral therapy was successful.
AB  - We report the case of a 25-year-old male Japanese homosexual with primary human
      immunodeficiency virus (HIV)-1 infection and early stage syphilis. Approximately
      60 days after HIV exposure by sex with another man, the patient abruptly had high
      fever, after which he experienced a variety of severe, prolonged symptoms such as
      painful oral mucosa ulcerations, rash, lymphadenopathy, splenomegaly, and a 5.5
      kg weight loss. Serum lactate dehydrogenase and liver biochemical test values
      were elevated. Antibodies to HIV by both enzyme-linked immunosorbent assay
      (ELISA) and Western blot (WB) test were negative at the time of symptom onset,
      but serum HIV-1 RNA level was 1 585 000 copies/ml. Antibody seroconversions were
      found on day 9 after the onset of symptoms by ELISA and on day 16 by WB test,
      suggesting primary HIV infection. Within 2 weeks of starting highly active
      antiretroviral therapy (HAART), all symptoms except lymphadenopathy were
      resolved, and the serum HIV-1 RNA level dramatically decreased to 5011 copies/ml,
      eventually becoming undetectable by the standard method. The patient has remained
      asymptomatic for the 18 months since symptom resolution after HAART, and HIV-1
      RNA remains undetectable.

PMID- 12525901
TI  - A clinical, serological, and immunological study in a Japanese traveler with
      dengue fever.
AB  - We describe the results of clinical, serological, and immunological studies in a
      Japanese traveler with dengue fever (DF). DF was confirmed by isolation of dengue
      virus from the serum, a positive direct reverse-transcription polymerase chain
      reaction (RT-PCR) test, and a high titer of anti-IgM antibody to dengue virus.
      Interestingly, in this patient infected by dengue virus serotype 3, we found a
      low CD4/CD8 ratio and a decrease in CD4 lymphocytes, a variation of cross
      reaction to dengue virus serotypes 1, 2, and 4, and high serum interferon-gamma
      levels just after a transient elevation of interleukin-12.

PMID- 12525902
TI  - Rapid pulsed-field gel electrophoresis technique for determination of genetic
      diversity of Serratia marcescens.
AB  - Seventeen Serratia marcescens strains were isolated from patients admitted to a
      hospital in the Tokyo metropolitan area. In order to study their genetic
      diversity, pulsed-field gel electrophoresis (PFGE) was performed. Clear bands
      were not observed by the standard PFGE technique following the instruction manual
      from the company. To obtain clear results, it was necessary to include some
      additional steps to the preparation of PFGE samples. We added an inactivation
      step for DNase using formaldehyde, and the bacterial strains were embedded in
      thinner plug molds than usual. These modifications were effective with all
      strains, and the complete PFGE pattern was obtained in the samples treated with
      formaldehyde and using thin plug molds. We established a rapid method to obtain a
      high-quality PFGE result for S. marcescens.

PMID- 12525903
TI  - Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of
      multidrug efflux systems, MexAB-OprM, MexCD-OprJ, and MexXY/OprM to carbapenems:
      substrate specificities of the efflux systems.
AB  - Overproduction of multidrug efflux systems MexAB-OprM, MexCD-OprJ, and MexXY/OprM
      of Pseudomonas aeruginosa caused reduction of susceptibility of the mutant, which
      lacked AmpC and all three systems to panipenem, meropenem, S4661 and DU6681a;
      meropenem, S4661 and DU6681a; and BO2727, panipenem, meropenem, S4661 and
      DU6681a, respectively, but not reduction of the susceptibility to imipenem and
      biapenem. Thus, we determined substrate specificities of these efflux systems to
      carbapenems.

PMID- 12525904
TI  - Usefulness of a colorimetric method for testing antifungal drug susceptibilities
      of Aspergillus species to voriconazole.
AB  - The usefulness of a colorimetric method using Alamar Blue (Alamar Blue method)
      for susceptibility testing of Aspergillus species to voriconazole and three
      existing antifungal agents, itraconazole (ITCZ), flucytosine (5-FC), and
      amphotericin B (AMPH-B), was studied using four ATCC strains of three species,
      including two strains of A. fumigatus and one each of A. flavus and A. niger. For
      comparison, the broth microdilution method for antifungal susceptibility testing
      of filamentous fungi proposed by the National Committee for Clinical Laboratory
      Standards (NCCLS method M38-P) was also used. Minimum inhibitory concentration
      (MIC) endpoints were read spectrophotometrically for the Alamar Blue method and
      visually for the NCCLS method after 46-50 h. Like the NCCLS method, Alamar Blue
      produced highly reproducible results for all the drugs and strains tested; most
      MIC values obtained by nine tests were within the range of 2 twofold dilutions
      for each strain. Voriconazole and ITCZ susceptibility testing with the Alamar
      Blue method and the NCCLS method yielded comparable results in 94% of the tests,
      meaning that the endpoints obtained were identical or differed by no more than 2
      twofold dilutions. On the other hand, susceptibility testing for 5-FC and AMPH-B
      yielded scores of 25% and 64%, respectively. Our study suggests the potential
      value of the Alamar Blue method as a convenient alternative to the NCCLS M38-P
      method for routine testing of Aspergillus species susceptibility to at least
      voriconazole and ITCZ.

PMID- 12525905
TI  - A clinical, serological, and immunological study in a Japanese traveler with
      dengue fever.

PMID- 12525906
TI  - Sutureless colonic anastomosis in the rat: a randomized controlled study.
AB  - The aim of the present study was to evaluate the effect of glue tissue on the
      healing of colonic anastomosis in rats. Two groups of 20 Wistar rats each were
      used. Following laparotomy, a segment of 1 cm of the colon was resected, 10 cm
      from the ileocecal valve. In the control group, the anastomosis was sutured in a
      single layer with 6-0 polypropylene interrupted extramucosal sutures. In the glue
      group, the anastomosis was performed by using 2-octyl cyanoacrylate (Dermabond,
      Ethicon). Rats were sacrificed on day 7 following operation. Integrity of the
      anastomoses, existence of perianastomotic abscess or peritonitis, and adhesion
      formation were recorded. Anastomoses were resected including a 2.5-cm of bowel on
      either side. Bursting pressures were measured and the specimens were sent for
      histological examination. Anastomotic dehiscence occured in 20% of the animals in
      each group. Adhesion formation was more extensive in the glue group compared to
      the control group, but this difference was not statistically significant
      (p=0.074). Bursting pressures of the anastomoses between the two groups were not
      statistically significant (p=0.897). The wound healing process, as assessed by
      inflammatory cell infiltration, blood vessel neodevelopment, collagen deposition
      and fibroblast activity, did not differ statistically between the two groups
      (p>0.05). In conclusion, 2-octyl cyanoacrylate provides, under experimental
      conditions, a sutureless anastomosis equal in healing to the conventionally
      sutured one. The outcome may differ under demanding clinical situations.

PMID- 12525907
TI  - Sacral nerve neuromodulation improves physical, psychological and social quality
      of life in patients with fecal incontinence.
AB  - There are several therapeutic options for fecal incontinence but often they do
      not achieve good results in the long run. This study dealt with sacral nerve
      modulation, a new therapeutic option. Twenty-one patients underwent pudendal
      nerve evaluation (PNE) at our institution. Nine patients were affected by both
      fecal and urinary incontinence, 3 had fecal incontinence and anal pain, 5 had
      fecal incontinence and pelvic floor dyssynergia, and 4 had isolated fecal
      incontinence. They underwent morphological, functional and psychological tests
      prior to PNE, showing no sphincter rupture, almost normal anal pressures,
      impaired rectal sensation and deficient psychological pattern. All patients
      underwent at least two nerve evaluations. Four of 21 patients (19%) were selected
      to receive a permanent sacral electrode, as PNE seemed to have improved their
      symptoms by >75%. A median follow-up of 15 months (range, 6-24 months) showed
      that this method decreases weekly episodes of incontinence and increases maximal
      squeeze pressure. We demonstrated an increase in basal pressure in 3 of 4
      patients (all with isolated fecal incontinence). Rectal sensation threshold
      decreased in three patients; urge threshold decreased in two patients and
      increased in two patients, but in each patient we got a stabilization. We
      evaluated the quality of life by applying the Short Form Health Survey test (SF
      36). All 4 patients showed a significant increase in the scores of physical,
      emotional and social role functioning after the permanent implant. In conclusion,
      sacral nerve modulation may improve physical, physiological and social quality of
      life in selected groups of incontinent patients without gross sphincter lesions
      and with impaired rectal sensation.

PMID- 12525908
TI  - Low anterior resection without defunctioning stoma.
AB  - The aim of our study was to determine the anastomotic leakage rate after the
      performance of low anterior resection without protective stoma. During the time
      period from 1989 to 2001, 82 consecutive patients underwent low anterior
      resection for rectal carcinoma without protective stoma. Thirteen anastomoses
      were hand sewn (15.8%) and the remaining 69 (84.2%) were constructed with the use
      of a circular stapling gun. The mean distance of the anastomoses from the anal
      margin was 6.2 cm (range, 3-9 cm). None of the 82 low anterior resections was
      covered by a defunctioning stoma. Clinical anastomotic leakage occurred in 4
      patients (4.9%) and 4 other patients presented radiologically detected leakage
      (4.9%). No death occurred in the 8 patients that presented anastomotic
      dehiscence. Non-specific complications were detected in 11 (13.4%) of 82
      patients. In conclusion, the low leakage rate of the anastomoses in our patients
      allows us to recommend low anterior resection without defunctioning stoma.

PMID- 12525909
TI  - Percutaneous postoperative intra-abdominal abscess drainage after elective
      colorectal surgery.
AB  - Intra-abdominal abscesses are a frequent source of morbidity and mortality
      following both elective and emergent surgery of the alimentary tract. CT-guided
      percutaneous drainage of intra-abdominal abscess is an alternative to immediate
      surgical intervention. We studied the clinical characteristics and outcomes of
      patients undergoing percutaneous drainage of intra-abdominal abscesses arising
      after elective colorectal procedures. We retrospectively identified 40 patients
      with postoperative intraabdominal abscess following elective colorectal surgery
      who underwent CT-guided percutaneous drainage with a Von Sonnenberg sump drain
      between 1990 and 1998. The most common presenting symptoms were pyrexia in 39
      (97%), abdominal tenderness in 32 (80%), guarding in 1 (2.5%) and abdominal mass
      in 3 (7.5%); no patient had generalized peritonitis. The most common index
      procedure was proctocolectomy with ileoanal anastomosis and ileal Jpouch in 12
      (30%) patients. Drainage was performed using an anterior approach in 32 (80%) and
      a transgluteal window in 8 (20%) patients. Thirty-five (87.5%) patients had a
      single collection, while 2 (5.0%) patients had 2 collections and 3 (7.5%)
      patients had 3 collections. Thirteen (32.5%) patients had perioperative steroids,
      30 (75%) had preoperative antibiotics, and 40 (100%) had postoperative
      antibiotics. Follow-up at a mean of 35.8 days revealed complete resolution of
      abscess in 26 (65%) patients; 14 (35%) patients had residual or recurrent abscess
      successfully treated by repeat drainage in 8 patients and requiring laparotomy in
      6. Percutaneous CT-guided abscess drainage is an effective method for treating
      intra-abdominal abscess following elective colorectal surgery. The primary
      success was 65% after the first and 85% after a second drainage. In conclusion,
      this technique should be considered as the treatment of choice in patients with
      localized intra-abdominal abscess without signs of generalized peritonitis.

PMID- 12525910
TI  - Excision and marsupialization versus sinus excision for the treatment of limited
      chronic pilonidal disease: a prospective, randomized trial.
AB  - The treatment techniques for pilonidal disease are either associated with high
      recurrence rates or complex procedures. This prospective randomized study
      compared the outcome of excision and marsupialization technique with sinus
      excision technique. A total of 40 consecutive patients with limited, chronic
      pilonidal sinus disease were operated with either excision and marsupialization
      technique (Group 1, n=20) or sinus excision technique (Group 2, n=20). The
      demographics, perioperative data, complications and recurrences were recorded.
      Patient satisfaction was evaluated with a specific questionnaire 16-18 weeks
      after surgery. Demographic data, preoperative symptoms and the acute disease
      history were similar between the groups. Operation time, hospital stay and work
      off periods were significantly shorter and the number of out-patient procedures
      was significantly more in Group 2. Although satisfaction scores were similar
      between the groups, the patients who had no complaint, were "completely
      satisfied" or would "absolutely recommend the operative technique to other
      patients" were significantly more in Group 2. In conclusion, the sinus excision
      technique requires a shorter operation time, hospital stay and work-off period
      than excision and marsupialization in the treatment of limited, chronic pilonidal
      disease. The sinus excision technique can be performed as an out-patient
      procedure in most cases, and seems to be associated with better patient
      satisfaction.

PMID- 12525911
TI  - Randomised trial comparing LigaSure haemorrhoidectomy with the diathermy
      dissection operation.
AB  - The study was designed to compare LigaSure haemorrhoidectomy with open
      haemorrhoidectomy performed by means of diathermy excision. Fifty-sixty
      consecutive patients with third- and fourth-degree haemorrhoids were randomly
      allocated to undergo either LigaSure haemorrhoidectomy (29 patients) or diathermy
      haemorrhoidectomy (27 patients). All patients were evaluated for operative time,
      pain, post-operative analgesic requirements, time to first bowel movement, length
      of hospital stay, wound healing period, time to return to work, and occurrence of
      early postoperative complications (such as urinary dysfunction, bleeding,
      soiling, seepage, continence disorders) and late complications (such as
      stenosis). A statistically significant advantage was observed in the patients who
      received the LigaSure technique as far as concerns length of operative time (9.2
      vs. 12.2 min, p<0.001), post-operative analgesic requirements (14.1 vs. 16.8
      administrations, p<0.001), wound healing period (16.3 vs. 37.5 days, p< 0.0001),
      and time to return to work (8.3 vs. 18.3 days, p<0.01). No significant difference
      was seen in the postoperative pain score, complications rate, first bowel motion
      or hospital stay. No recurrence was observed at the 6-month follow-up. In
      conclusion, our experience shows that the LigaSure haemorrhoidectomy offers
      definite advantages over the classic diathermy technique. This procedure is
      easier, safer, and more rapid to perform and is followed by a faster wound
      healing time, a significantly shorter hospital stay, less postoperative pain and
      faster wound healing.

PMID- 12525912
TI  - Large bowel perforation: morbidity and mortality.
AB  - Perforations of large bowel are rare but severe complications, mainly of
      colorectal cancer and colonic diverticulitis. The choice of the surgical
      procedure is still debated. We retrospectively studied peritonitis caused by
      large bowel perforation to assess predictors of mortality and safety of primary
      resection and anastomosis. We investigated 59 patients with large bowel
      perforation treated surgically as emergency cases: 18 patients underwent primary
      resection and anastomosis, 36 had primary resection of the diseased part of bowel
      without anastomosis, and 5 patients had non-resective procedures. The severity of
      peritonitis was assessed using Hinchey's classification and the Mannheim
      peritonitis index (MPI). Overall mortality was 16.9%. MPI score was significantly
      lower for survivors vs. non-survivors, and for patients with resection and
      anastomosis vs. those who underwent resection without anastomosis (p<0.001). The
      mortality rate was 11.1% for primary resection with anastomosis, and 22.2% for
      primary resection without anastomosis. No patient with MPI less than 25 died,
      while 10 (38.5%) of the patients with MPI of 26-36 died. In conclusion, a radical
      aggressive approach is recommended for most patients with large bowel
      perforation. Mortality and morbidity are closely related to the extent of
      intraperitoneal infection and the incidence of postoperative complications is
      higher in patients with perforation due to non-malignant causes.

PMID- 12525913
TI  - Secondary reconstruction of an ileal reservoir in patients with failed straight
      ileoanal pull-through: report of two cases.
AB  - The ileoanal reservoir is a widely accepted option for the treatment of mucosal
      ulcerative colitis and familial adenomatous polyposis. Function of an ileoanal
      anastomosis without the reservoir may be unacceptable. The aim of this study was
      to assess the technical feasibility of conversion of a straight ileoanal
      anastomosis to an ileoanal reservoir anastomosis. Two patients underwent straight
      ileoanal anastomosis and then underwent subsequent conversion to an ileoanal
      reservoir anastomosis. A 16-year-old girl with mucosal ulcerative colitis and a
      38-year-old woman with familial adenomatous polyposis presented with 20-25 bowel
      movements per day and severe diarrheal-related symptoms within 11 months of
      ileoanal anastomosis. In each case, the anastomosis was reversed and an ileal
      Jpouch was fashioned and anastomosed to the dentate line; there was no
      postoperative morbidity. The 38-year-old patient reported 4-5 bowel movements per
      day without the need for any medication at 1-8 months after ileostomy closure.
      The 16-year-old patient is waiting ileostomy closure. In conclusion, it is
      technically possible to convert a straight ileoanal anastomosis to an ileoanal
      reservoir anastomosis with expectations of improvement in function.

PMID- 12525914
TI  - Laparoscopic giant parastomal hernia repair with prosthetic mesh.
AB  - Laparoscopy is being increasingly used in colorectal surgery interventions.
      Herein, we present a patient with giant parastomal hernia who underwent
      laparoscopic repair. A70-year-old man who had undergone abdominoperineal
      resection and end colostomy for carcinoma of rectum was admitted to our clinic
      with a giant parastomal hernia. The parastomal hernia was repaired by
      laparoscopic approach using prosthetic material. The patient was discharged
      uneventfully on postoperative day 4. Laparoscopic approach is a rational
      alternative to conventional repair techniques of parastomal hernia and may be a
      reliable and easily applicable method with the classic benefits of laparoscopic
      surgery.

PMID- 12525915
TI  - Modified stapled haemorrhoidopexy for the treatment of massive circumferentially
      prolapsing piles.
AB  - Stapled haemorrhoidopexy is becoming the procedure of choice for the treatment of
      symptomatic prolapsing piles. However, it can be technically difficult if the
      piles are massively enlarged and prolapsing circumferentially through the anal
      canal. We describe a novel method that combines both diathermy and stapled
      excision, producing complete haemorrhoidal eradication with anorectal mucosal
      fixation above the dentate line.

PMID- 12525916
TI  - Outpatient treatment of hemorrhoids with a combined technique: results in 7850
      cases.
AB  - A combination of sclerotherapy, rubber band ligation and infrared coagulation was
      performed in 7850 patients seen an outpatient clinic over a period of 9 years.
      The most common symptom was bleeding followed by prolapse, pain and itching.
      Results were considered satisfactory in 7100 patients (90.5%); 750 (9.5%)
      required a formal hemorrhoidectomy. Complications were mild to moderate pain in
      1777 cases (22.6%), severe pain in 157 cases (2.2%), mild hemorrhage in 199
      (2.5%) and hemorrhage requiring transfusion in 10 cases (0.1%). In conclusion,
      non-surgical outpatient treatment has a great impact on patient's perception of
      the disease and results in considerable savings for the healthcare system.

PMID- 12525917
TI  - Laboratory diagnosis of human herpesvirus 8 infection in humans.
AB  - Human herpesvirus 8 (HHV-8) is causally associated with Kaposi's sarcoma, primary
      effusion lymphoma and multicentric Castleman's disease. Serological and molecular
      biology assays are used to investigate the biology of this virus in different
      populations and diseases. Serological assays are mainly used to study the
      prevalence of the viral infection and to predict the diagnosis of Kaposi's
      sarcoma and other HHV-8-associated cancers. The appearance of antibodies against
      lytic antigens precedes the appearance of antibodies against latent antigens,
      probably explaining the lower sensitivity of assays based on latent HHV-8
      antigens. The lack of international reference serum panels is presently the major
      bottleneck for further progress in the field of HHV-8 serology. Molecular
      biological assays are an absolute requirement for both the diagnosis and the
      follow-up of HHV-8 infection. Qualitative methods have been particularly useful
      to elucidate the mode of transmission and the causal association between HHV-8
      and HHV-8-associated diseases. Quantitative methods have become an essential tool
      to monitor the progression of the infection and the effects of antiviral
      therapies. This review analyzes the performance of the different serological and
      molecular biological assays available at present. The main conclusion is that
      more research is needed to define the most useful laboratory tests for the
      diagnosis of HHV-8 infection and to establish the clinical role of such tests.

PMID- 12525918
TI  - Factors related to persistence of Legionella urinary antigen excretion in
      patients with legionnaires' disease.
AB  - The aim of this prospective study was to compare patient characteristics,
      clinical data, and evolution of Legionella pneumophila pneumonia according to the
      duration of Legionella urinary antigen excretion. Urine samples from 61 patients
      with Legionella pneumonia diagnosed by detection of urinary antigen were obtained
      periodically until urinary antigen could no longer be detected. Cases were
      divided into two groups based on the duration of urinary antigen excretion: group
      I (46 patients, <60 days) and group II (15 patients, >or=60 days). Groups were
      compared for patient characteristics, clinical data, and evolution of pneumonia.
      Antigen excretion >or=60 days was observed significantly more frequently in
      immunosuppressed patients ( P=0.001) in whom the time to apyrexia was >72 h (
      P=0.002), although only the time to apyrexia remained significant on multivariate
      analysis ( P=0.006). In conclusion, the duration of Legionella urinary antigen
      excretion was <60 days in most patients but was longer in immunosuppressed
      patients with a longer time to defervescence of fever.

PMID- 12525919
TI  - Prevalence and drug susceptibility of pathogens causing bloodstream infections in
      northern Italy: a two-year study in 16 hospitals.
AB  - The epidemiology of bacterial pathogens causing bloodstream infection was studied
      in 16 hospitals in Lombardy (northern Italy) over a 2-year period (1999 and
      2000). Overall, 2924 microorganisms causing significant bacteremia were
      collected. The most frequent isolates were Escherichia coli ( n=663; 22.7%),
      Staphylococcus aureus ( n=534; 18.3%), Staphylococcus epidermidis ( n=242; 8.2%),
      and Pseudomonas aeruginosa ( n=176; 6.0%). Unlike Escherichia coli, which was
      usually acquired from the community, Staphylococcus aureus, Staphylococcus
      epidermidis, and Pseudomonas aeruginosa were usually acquired in hospitals. Rates
      of resistance to oxacillin and its associated traits were significantly higher
      among hospital-acquired staphylococci as compared to those of isolates from the
      community. Escherichia coli was highly susceptible to extended-spectrum
      cephalosporins, with a very low percentage of strains producing extended-spectrum
      ss-lactamases (ESBLs). On the contrary, production of ESBL appeared to be an
      important mechanism of resistance among nosocomial isolates of Klebsiella
      pneumoniae. Resistance to ciprofloxacin was widespread in several members of the
      family Enterobacteriaceae, with rates often exceeding 10%. Moreover, with regard
      to ciprofloxacin, there were no significant differences between rates of
      resistance among Enterobacteriaceae causing hospital-acquired infections versus
      those causing community-acquired infections. Multidrug resistance was commonly
      observed in Pseudomonas aeruginosa, indicating the need for new antimicrobial
      agents that are more active against nonfermentative gram-negative bacteria. In
      conclusion, epidemiological studies of the prevalence and antimicrobial
      susceptibility patterns of blood isolates in northern Italy appear to provide
      useful information for both empirical treatment of suspected infections and
      better management of patients.

PMID- 12525920
TI  - Do HIV-seropositive patients become colonised with drug-resistant microorganisms?
AB  - The aim of the present study was to investigate whether HIV-infected patients, a
      group that is supposedly at risk for infection with antibiotic-resistant
      microbes, really does so, and to assess possible risk factors for acquiring these
      organisms. During the period from January 1998 to July 1999, samples of normal
      flora were obtained from 107 HIV-infected patients attending an outpatient clinic
      in Oslo, Norway. The samples were cultured for Streptococcus pneumoniae,
      Haemophilus influenzae, Escherichia coli, coagulase-negative staphylococci and
      Candida spp., and the resulting isolates were tested for antimicrobial
      susceptibility. The patients studied represented all stages of HIV infection,
      from recently infected to severely immunocompromised. Samples were taken at one,
      two or three time-points to determine whether antimicrobial resistance in
      colonising microorganisms increases over time. Antimicrobial resistance was
      linked primarily to antimicrobial prophylaxis, but it did not increase during the
      observation period. The level of a patient's immunodeficiency and the
      consequently intensified medical care was also of some importance. Even though
      about 50% of the patients were receiving antimicrobial agents at the time of
      sampling, the level of resistance found in these patients was very similar to
      that found in other patient groups in Norway; except for Candida albicans
      isolates, which were less susceptible to fluconazole. Overall, antimicrobial
      resistance was uncommon in the HIV-seropositive patients studied, a finding that
      is probably related to the overall low prevalence of antimicrobial resistance in
      the general population in Norway.

PMID- 12525921
TI  - Clinical study of 44 cases of Staphylococcus aureus meningitis.
AB  - In order to describe the clinical features and outcome of Staphylococcus aureus
      meningitis, the charts of 44 cases seen at one teaching hospital during a 20-year
      period were retrospectively reviewed. Staphylococcus aureus was the fifth most
      common cause of bacterial meningitis (10.2% of cases). There were 28 (63%) cases
      of postoperative meningitis and 16 (37%) of spontaneous meningitis. Patients with
      postoperative meningitis were younger than patients with spontaneous meningitis
      (mean age, 40.3 vs. 59.3 years; P=0.04) and had a lower frequency of community
      acquired infection (32.1% vs. 93.8%; P<0.01), severe underlying diseases (28% vs.
      87%; P<0.01) and associated staphylococcal infection (35% vs. 75%; P=0.01). The
      clinical presentation was similar in both groups, but patients with postoperative
      meningitis had a lower frequency of altered mental status (39% vs. 75%; P=0.02),
      meningeal signs (28% vs. 62%; P=0.02), petechial rash (0% vs. 18%; P=0.04),
      bacteremia (7% vs. 75%; P<0.01), and septic shock (0% vs. 44%; P<0.01). Most
      patients were treated with cloxacillin or vancomycin, with or without rifampicin,
      for a mean period of 22.5 days (range, 1-100 days). Overall mortality was 27%,
      and the mortality rate was higher for cases of spontaneous than postoperative
      meningitis (50% vs. 14%; P=0.01). Mortality correlated significantly with
      advanced age, spontaneous meningitis, altered mental status, and the presence of
      severe underlying diseases, bacteremia, and septic shock.

PMID- 12525922
TI  - Evaluation of the Vitek 2 system for rapid identification of clinical isolates of
      gram-negative bacilli and members of the family Streptococcaceae.
AB  - Accuracy of the Vitek 2 automated system (bioMerieux Vitek, USA) for rapid
      identification of bacteria was evaluated using a collection of 858
      epidemiologically unrelated gram-negative and 99 gram-positive clinical isolates.
      Isolates were tested after subculturing to ensure purity. Conventional agar-based
      biochemical tests (Steers replicator) were used as a reference method of
      identification. Gram-negative bacteria were identified to the species level with
      95.3% accuracy by the system ( Enterobacteriaceae, 95.9%; and non-
      Enterobacteriaceae, 92.5%), and gram-positive isolates with 72% accuracy.
      Although Vitek 2 identified routine clinical isolates of gram-negative bacilli
      and Enterococcus faecalis and Enterococcus faecium reliably, rapidly, and
      reproducibly, improvement is required in the identification of less common
      species of enterococci and viridans group streptococci.

PMID- 12525923
TI  - Evaluation of the BactiCard Neisseria for identification of pathogenic Neisseria
      species and Moraxella catarrhalis.
AB  - The BactiCard Neisseria (Remel, USA) is a chromogenic enzyme substrate system for
      identifying Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria lactamica,
      and Moraxella catarrhalis. The identification system consists of a card with four
      test circles impregnated with chromogenic substrates for indoxyl butyrate
      esterase (IB), prolyl aminopeptidase (PRO), gamma-glutamyl aminopeptidase (GLUT),
      and ss-galactosidase (BGAL). These substrates permit the identification of
      Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, and
      Neisseria lactamica, respectively. After hydration of the circles with buffer,
      colonies from growth on selective media or a subculture are applied to the four
      circles. IB and BGAL reactions are read for a blue-green color after 2 and 15
      min, respectively. PRO and GLUT reactions are read at 15 min for a red color
      after addition of a developer reagent. Identifications obtained with the
      BactiCard Neisseria were compared with those obtained using conventional
      procedures for 558 isolates in a blinded fashion. The BactiCard Neisseria
      identified 100% of 254 Neisseria gonorrhoeae, 100% of 125 Neisseria meningitidis,
      53 (98.2%) of 54 Neisseria lactamica, and 123 (98.4%) of 125 Moraxella
      catarrhalis isolates. The BactiCard Neisseria is an accurate and rapid system for
      identification of these microorganisms in the clinical laboratory.

PMID- 12525924
TI  - Diversity of Staphylococcus aureus strains isolated from two European regions
      with different prevalences of methicillin resistance.
AB  - The genodiversity of Staphylococcus aureus isolates from the Nottingham region of
      the United Kingdom was compared with isolates from the Freiburg region of
      Germany. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA)
      isolates was higher in Nottingham than in Freiburg. In patients from Nottingham
      hospitals, 80% of MRSA isolates were classical epidemic MRSA-15, but genotypic
      variants of epidemic MRSA-15 comprised 72% of isolates from Nottingham community
      based patients. In contrast, MRSA isolates from Freiburg showed greater
      diversity, but 47% and 23% of isolates, respectively, belonged to two predominant
      MRSA genotypes found in isolates from both hospitalised and community-based
      patients. The results suggest that genodiversity becomes increasingly more
      confined in settings with a higher frequency and longer duration of MRSA
      prevalence.

PMID- 12525925
TI  - Liver abscesses due to Fusobacterium spp that mimick malignant metastatic liver
      disease.
AB  - A 71-year-old man presented with the clinical and radiological features of
      metastatic liver disease but subsequently was found to have multiple liver
      abscesses caused by Fusobacterium necrophorum. At liver biopsy, pus was aspirated
      and Fusobacterium necrophorum was isolated from the pus. Serial blood cultures
      and urine cultures were sterile and negative for Fusobacterium spp. The patient
      made a complete recovery in response to treatment with penicillin and
      amoxicillin. This case illustrates the importance of liver abscesses as an
      uncommon but completely treatable differential diagnosis for the radiological
      appearances of multiple hepatic lesions.

PMID- 12525926
TI  - Retrospective analysis of the first clonal outbreak of nalidixic acid-resistant
      Shigella sonnei shigellosis in Israel.
AB  - Reported here is a retrospective molecular analysis of the isolates recovered
      from the first outbreak of nalidixic acid (NA)-resistant Shigella sonnei
      shigellosis to occur in Israel. The outbreak affected 94 children. In the
      retrospective analysis, a total of 13 NA-resistant isolates and five NA
      susceptible isolates recovered during the outbreak period were examined.
      Restriction fragment length polymorphism profiles obtained by digestion with
      BamHI, PvuI, HinfI or SmaI yielded identical profiles for all 18 isolates. All NA
      resistant strains had an identical plasmid profile, but this profile differed
      from that displayed by the susceptible strains. In all of the NA-resistant
      strains a 304 bp fragment in the gyrA gene coding for a region associated with NA
      resistance was sequenced and showed a single point mutation, Ser83-->Phe. In this
      outbreak, the isolates of NA-resistant Shigella sonnei belonged to a single clone
      and NA resistance was associated with a point mutation in the gyrA gene.

PMID- 12525927
TI  - Eikenella corrodens infective endocarditis in a previously healthy non-drug user.
AB  - Reported here is a case of Eikenella corrodens aortic valve infective
      endocarditis presenting as a stroke in a previously healthy 31-year-old man. The
      patient had no evidence of structural heart disease and reported no history of
      intravenous drug use or recent dental treatment. There are no other cases
      reported in the available literature in which this microorganism has caused
      endocarditis in the absence of recognised risk factors.

PMID- 12525929
TI  - Late reactivation of calcified granuloma in a patient with chronic suppurative
      brucellosis.

PMID- 12525928
TI  - Use of voriconazole to successfully treat disseminated Trichosporon asahii
      infection in a patient with acute myeloid leukaemia.
AB  - Trichosporon spp. is an emerging fungal pathogen in immunocompromised hosts, and
      disseminated infection is often fatal in neutropenic patients. Reported here is a
      case of disseminated infection in a neutropenic patient with acute leukaemia.
      After failure of amphotericin B and fluconazole therapy, the course of infection
      dramatically improved with voriconazole treatment. A literature search revealed
      69 additional cases of disseminated Trichosporon spp. infections in neutropenic
      patients, and these are also reviewed. Clinical symptoms that suggest infection
      include fever, disseminated papulopustular cutaneous lesions and pulmonary
      involvement. Despite treatment with antifungal agents (amphotericin B,
      fluconazole), 78% of patients died. Voriconazole may represent a promising
      therapy for this life-threatening infection.

PMID- 12525930
TI  - Retrospective identification of three undiagnosed cases of measles encephalitis.

PMID- 12525932
TI  - Development of a biologically-based controlled growth and differentiation model
      for developmental toxicology.
AB  - Amathematical model is developed with a highly controlled birth and death process
      for precursor cells. This model is both biologically- and statistically-based.
      The controlled growth and differentiation (CGD) model limits the number of
      replications allowed in the development of a tissue or organ and thus, more
      closely reflects the presence of a true stem cell population. Leroux et al.
      (1996) presented a biologically-based dose-response model for developmental
      toxicology that was derived from a partial differential equation for the
      generating function. This formulation limits further expansion into more
      realistic models of mammalian development. The same formulae for the probability
      of a defect (a system of ordinary differential equations) can be derived through
      the Kolmogorov forward equations due to the nature of this Markov process. This
      modified approach is easily amenable to the expansion of more complicated models
      of the developmental process such as the one presented here. Comparisons between
      the Leroux et al. (1996) model and the controlled growth and differentiation
      (CGD) model as developed in this paper are also discussed.

PMID- 12525933
TI  - Deterministic extinction effect of parasites on host populations.
AB  - Experimental studies have shown that parasites can reduce host density and even
      drive host population to extinction. Conventional mathematical models for
      parasite-host interactions, while can address the host density reduction
      scenario, fail to explain such deterministic extinction phenomena. In order to
      understand the parasite induced host extinction, Ebert et al. (2000) formulated a
      plausible but ad hoc epidemiological microparasite model and its stochastic
      variation. The deterministic model, resembles a simple SI type model, predicts
      the existence of a globally attractive positive steady state. Their simulation of
      the stochastic model indicates that extinction of host is a likely outcome in
      some parameter regions. A careful examination of their ad hoc model suggests an
      alternative and plausible model assumption. With this modification, we show that
      the revised parasite-host model can exhibit the observed parasite induced host
      extinction. This finding strengthens and complements that of Ebert et al. (2000),
      since all continuous models are likely break down when all population densities
      are small. This extinction dynamics resembles that of ratio-dependent predator
      prey models. We report here a complete global study of the revised parasite-host
      model. Biological implications and limitations of our findings are also
      presented.

PMID- 12525935
TI  - Feedback control for chemostat models.
AB  - It is shown that a chemostat with two organisms can be made coexistent by means
      of feedback control of the dilution rate. Remaining freedom in the feedback law
      can be used to guarantee robustness or improve particular performance indices.
      Unfortunately a topological property prevents coexistence by feedback control for
      chemostats with more than two organisms. We apply our results to control
      bioreactors aimed at producing commercial products through genetically altered
      organisms. In all our results the coexistence takes its simplest form: a global
      asymptotically stable equilibrium point in the interior of the non-negative
      orthant.

PMID- 12525934
TI  - Coexistence of different serotypes of dengue virus.
AB  - We formulate a non-linear system of differential equations that models the
      dynamics of dengue fever. This disease is produced by any of the four serotypes
      of dengue arbovirus. Each serotype produces permanent immunity to it, but only a
      certain degree of cross-immunity to heterologous serotypes. In our model we
      consider the relation between two serotypes. Our interest is to analyze the
      factors that allow the invasion and persistence of different serotypes in the
      human population. Analysis of the model reveals the existence of four equilibrium
      points, which belong to the region of biological interest. One of the equilibrium
      points corresponds to the disease-free state, the other three equilibria
      correspond to the two states where just one serotype is present, and the state
      where both serotypes coexist, respectively. We discuss conditions for the
      asymptotic stability of equilibria, supported by analytical and numerical
      methods. We find that coexistence of both serotypes is possible for a large range
      of parameters.

PMID- 12525936
TI  - Change in frequency of a rare mutant allele: a general formula and applications
      to partial inbreeding models.
AB  - We deduce and prove a general formula to approximate the change in frequency of a
      mutant allele under weak selection, when this allele is introduced in small
      frequency into a population which was previously at a fixation state. We apply
      the formula to autosomal genes in partial selfing models and to autosomal as well
      as sex-linked genes in partial sib mating models. It is shown that the fate of a
      rare mutant allele depends not only on the selection parameters, the inbreeding
      coefficient and the reproductive values of the sexes in sex-differentiated
      populations, but also on coefficients of relatedness between mates. This is
      interpreted as a kin selection effect caused by inbreeding per se.

PMID- 12525937
TI  - Percutaneous management of occlusive arterial disease associated with vasculitis:
      a single center experience.
AB  - The purpose of this study was to evaluate the safety and effectiveness of
      percutaneous transluminal angioplasty for occlusive arterial disease associated
      with vasculitis. Eleven patients (10 women, 1 man; ages 35-82 years) with the
      diagnosis of vasculitis of the large vessels underwent interventional treatment
      during intraarterial angiography. The causes included giant cell arteritis (n =
      8) and Takayasu arteritis (n = 3). Thirty-three occlusive lesions (including
      brachiocephalic and renal arteries, and arteries of upper and lower extremities)
      were treated with balloon angioplasty and/or stent placement. Follow-up included
      clinical examination, angiography, and color duplex ultrasound. Technical success
      was 100% (25/25) for stenoses and 50% (4/8) for occlusive lesions, representing
      all lesions combined from different anatomic locations. Dissection (n = 3) and
      arterial rupture with retroperitoneal hematoma (n = 1) was found in three
      patients. During follow-up (mean 12 months), restenoses (n = 8) and re-restenoses
      (n = 1) occurred in 8 vascular areas. Three of these lesions were treated with
      repeated PTA (n = 4). The cumulative primary clinical success rate was 67.6%,
      cumulative secondary success rate 74.4%, and cumulative tertiary success rate
      75.9%. Interventional therapy in systemic vasculitis provides promising results
      in technical success rates and followup. Angioplasty may result in arterial
      injury, but the rate of complications is low.

PMID- 12525938
TI  - MR arthrography: pharmacology, efficacy and safety in clinical trials.
AB  - OBJECTIVE: A meta-analysis was carried out of clinical trials published between
      1987 and 2001 in respect of the clinical pharmacology and safety as well as the
      diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular
      injection before MRI examination. DESIGN: Scientific papers (clinical, postmortem
      and experimental studies) and information from the manufacturer regarding intra
      articular injection of Gd-DTPA that addressed questions of mode of action,
      optimal concentration and dose, elimination and safety were reviewed. Clinical
      studies were classified according to their study design. The sensitivity,
      specificity and accuracy of MR arthrography (MRA) were compared with a "gold
      standard" (arthroscopy, arthrotomy) and other radiological evidence for different
      joints. RESULTS: Fifty-two clinical studies of the overall 112 studies addressed
      aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The
      shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even
      excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in
      most indications, especially for the shoulder and knee joints and induced
      extension of rotator cuff lesions, labrum abnormalities and postoperative
      meniscal tears. Two millimoles per liter has proven to be the best concentration
      for intra-articular administration of Gd-DTPA. After passive complete diffusion
      from the joint within 6-24 h, complete and rapid renal elimination takes place
      after intra-articular injection. Local safety proved to be excellent after intra
      articular administration of Gd-DTPA. Regarding systemic tolerance almost no side
      effects have been reported, but the same safety considerations apply for intra
      articular administration of Gd-DTPA as for intravenous injection. CONCLUSIONS:
      The diagnostic efficacy of intra-articular MRA in most clinical conditions
      affecting major joints is greater than that of plain MRI. In some diagnostic
      problems MRA achieves almost the same sensitivity and specificity as the surgical
      gold standard. Given a sterile application, the intra-articular administration of
      Gd-DTPA in a concentration of 2 mmol/l prior to MRI is a safe procedure.

PMID- 12525940
TI  - Longitudinal stress fracture: patterns of edema and the importance of the
      nutrient foramen.
AB  - DESIGN AND PATIENTS: We reviewed the MR appearances of six cases of longitudinal
      stress fracture of the lower extremity. RESULTS: One fracture was in the femur
      and five were in the tibia. Four of the tibial fractures showed edema starting in
      the mid-tibia at the level of the nutrient foramen with the fracture on the
      anteromedial cortex. The other tibial fracture started at the nutrient foramen.
      Three fractures (two tibial and the femur fracture) showed eccentric marrow
      edema; all fractures showed either eccentric periosteal reaction or soft tissue
      edema. CONCLUSION: Primary diagnosis of longitudinal stress fracture is made by
      finding a vertical cleft on one or more axial images. Secondary signs of position
      of the nutrient foramen and patterns of edema may be useful.

PMID- 12525939
TI  - Plantar calcaneal enthesophytes: new observations regarding sites of origin based
      on radiographic, MR imaging, anatomic, and paleopathologic analysis.
AB  - OBJECTIVE: To determine the relationship between sites of calcaneal plantar
      enthesophytes and surrounding fascial and soft tissue structures using routine
      radiography, MR imaging, and data derived from cadaveric and paleopathologic
      specimens. DESIGN AND PATIENTS: Two observers analyzed the MR imaging studies of
      40 ankles in 38 patients (35 males, 3 females; mean age 48.3 years) with plantar
      calcaneal enthesophytes that were selected from all the ankle MR examinations
      performed during the past year. Data derived from these MR examinations were the
      following: the size of the enthesophyte; its location in relation to the plantar
      fascia (PF) and flexor muscles; and the thickness and signal of the PF. The
      corresponding radiographs of the ankles were evaluated at a different time by the
      same observers for the presence or absence of plantar enthesophytes and, when
      present, their measurements. A third observer reviewed all the discordant
      observations of MR imaging and radiographic examinations. Two observers analyzed
      22 calcaneal specimens with plantar enthesophytes at an anthropology museum to
      determine the orientation of each plantar enthesophyte. MR imaging of a cadaveric
      foot with a plantar enthesophyte with subsequent sagittal sectioning was
      performed to provide further anatomic understanding. RESULTS: With regard to MR
      imaging, the mean size of the plantar enthesophytes was 4.41 mm (SD 2.4). Twenty
      (50%) enthesophytes were located above the PF, 16 (40%) between the fascia and
      abductor digiti minimi, flexor digitorum brevis and abductor hallucis muscles,
      and only one (3%) was located within the PF. In three (8%) cases the location was
      not determined. The size of enthesophytes seen with MR imaging and radiographs
      was highly correlated (P<0.01). The interobserver agreement for all measurements
      was good (Pearson >0.8, kappa >0.9). Eleven of the 22 bone specimens had plantar
      enthesophytes oriented in the direction of the abductor digiti minimi and 11
      oriented in the direction of the flexor digitorum brevis and PF. The cadaveric
      sections revealed different types of enthesophytes. CONCLUSIONS: Plantar
      calcaneal enthesophytes arise in five different locations: at the insertion sites
      of abductor digiti minimi and flexor digitorum brevis muscles; between the PF and
      these muscles; and, less frequently, within the PF and at the insertion site of
      the short plantar ligament.

PMID- 12525941
TI  - Posterior-anterior weight-bearing radiograph in 15 degree knee flexion in medial
      osteoarthritis.
AB  - OBJECTIVE: To evaluate the degree of knee flexion at which: (1) degenerative
      joint space narrowing is best seen, (2) the tibial plateau is best visualized and
      (3) the tibiofemoral angle is most correct, in order to assess the degree of
      flexion in the anteroposterior radiographic view that is most useful for
      assessing medial compartment osteoarthritis (OA) of the knee. DESIGN AND
      PATIENTS: We compared the conventional extended view of the knee and views at 15
      degrees, 30 degrees, and 45 degrees of flexion with respect to joint space
      narrowing, alignment of the medial tibial plateau (MTP), and tibiofemoral angles
      in 113 knees of 95 patients with medial osteoarthritis of the knee (22 men, 73
      women; mean age 67 years). RESULTS: At the midpoint and the narrowest point of
      the medial compartment, joint space narrowing values at 15 degrees, 30 degrees,
      and 45 degrees of flexion of the knee were smaller than that of the conventional
      extended view. Superimposition of the margins of the tibial plateau was
      satisfactory in 12% of patients in the conventional extended view, in 36% at 15
      degrees of flexion, in 20% at 30 degrees of flexion, and in 19% at 45 degrees of
      flexion of the knee. When the knee was at 15 degrees of flexion there was a
      smaller difference in the tibiofemoral angle, in comparison with the knee
      extended, than was the case at 30 degrees and 45 degrees of flexion in patients
      with medial OA. CONCLUSION: A posteroanterior view with 15 degrees of flexion of
      the knee was able to detect joint space narrowing accurately, to achieve good
      alignment of the MTP in the medial compartment, and to reduce the difference in
      tibiofemoral angle compared with a view of the knee in conventional extension,
      and may be an alternative view in cases of medial OA of the knee.

PMID- 12525942
TI  - Calcific myonecrosis: keys to early recognition.
AB  - Calcific myonecrosis is a rare, late sequela of trauma occurring almost
      exclusively in the lower extremity which may be confused with an aggressive
      primary neoplasm. The platelike mineralization pattern seen on radiographs is
      characteristic but not widely recognized by clinicians. Three cases of calcific
      myonecrosis are reported, unique in that two presented for care following
      infection and that one had extended to involve the muscle compartments of the
      foot, a previously unreported site.

PMID- 12525943
TI  - Unicompartmental muscle edema: an early sign of deep venous thrombosis.
AB  - The finding of muscle edema restricted to a single muscle compartment on MRI
      usually indicates a diagnosis of traumatic injury, myositis, denervation or
      neoplasm. This case demonstrates that deep venous thrombosis can also be the
      cause of isolated deep posterior compartment muscle edema in the calf and should
      be considered in the differential diagnosis even in the absence of diffuse soft
      tissue or subcutaneous edema.

PMID- 12525944
TI  - Anaerobic osteomyelitis of femoral head with intraosseous, intra-articular,
      bursal and muscle pneumatosis.
AB  - A case is presented of anaerobic osteomyelitis with intraosseous pneumatosis
      resulting in extension of gas in soft tissue structures and femur in a patient
      with mitral valve vegetation and bacteremia. The finding of intraosseous
      pneumatosis and its extension into the hip joint, iliopsoas bursa and subgluteus
      medius bursa is depicted. Intraosseous pneumatosis is a rare but concerning
      finding for osteomyelitis in the absence of a penetrating wound, recent surgery,
      biopsy or fracture.

PMID- 12525945
TI  - Cat-scratch disease osteomyelitis.
AB  - We report on a patient who presented with osteomyelitis of a rib and adjacent
      abscess as a rare and atypical manifestation of cat-scratch disease. Radiographic
      findings showed an osteolytic lesion with adjacent mass. Biopsy, serology and
      polymerase chain reaction technique are essential for the final diagnosis.
      Prognosis is excellent with full recovery.

PMID- 12525946
TI  - Eosinophilic fasciitis in a military recruit: MRI evaluation with clinical
      correlation.
AB  - Eosinophilic fasciitis (EF) is an uncommon connective tissue disease. We report a
      patient with EF who presented with episodic swelling and stiffness of his legs
      and forearms in combination with peripheral eosinophilia. Imaging studies of the
      legs and forearms, including computed tomography (CT) and magnetic resonance
      imaging (MRI), clearly demonstrated the characteristic finding of fascial
      thickening. The complete clinical imaging and pathological findings are described
      in this report. Cross-sectional imaging is useful in diagnosing EF and in the
      appropriate clinical scenario may be helpful in differentiating EF from other
      connective tissue diseases.

PMID- 12525947
TI  - Multiparametric MR assessment of pediatric brain tumors.
AB  - MR assessment of pediatric brain tumors has expanded to include physiologic
      information related to cellular metabolites, hemodynamic and diffusion
      parameters. The purpose of this study was to investigate the relationship between
      MR and proton MR spectroscopic imaging in children with primary brain tumors.
      Twenty-one patients (mean age 9 years) with histologically verified brain tumors
      underwent conventional MR imaging, hemodynamic MR imaging (HMRI) and proton MR
      spectroscopic imaging (MRSI). Fourteen patients also had diffusion-weighted MR
      imaging (DWMRI). Metabolic indices including choline-containing compounds (Cho),
      total creatine (tCr) and lipids/lactate (L) were derived by proton MRSI, relative
      cerebral blood volume (rCBV) by HMRI, and apparent tissue water diffusion
      coefficients (ADC) by DWMRI. Variables were examined by linear regression and
      correlation as well as by ANOVA. Cho (suggestive of tumor cellularity and
      proliferative activity) correlated positively with rCBV, while the relationship
      between Cho and ADC (suggestive of cellular density) was inverse ( P<0.001). The
      relationship between rCBV and ADC was also inverse ( P=0.004). Cho and lipids
      (suggestive of necrosis and/or apoptosis) were not significantly correlated (
      P=0.51). A positive relationship was found between lipids and ADC ( P=0.002). The
      relationships between Cho, rCBV, ADC and lipids signify that tumor physiology is
      influenced by the tumor's physical and chemical environment. Normalized Cho and
      lipids distinguished high-grade from low-grade tumors ( P<0.05). Multiparametric
      MR imaging using MRSI, HMRI and DWMRI enhances assessment of brain tumors in
      children and improves our understanding of tumor physiology while promising to
      distinguish higher- from lower-malignancy tumors, a distinction that is
      particularly clinically important among inoperable tumors.

PMID- 12525948
TI  - Collateral circulation is an independent radiological predictor of outcome after
      thrombolysis in acute ischaemic stroke.
AB  - We tested the hypothesis that the type of vascular occlusion, recanalisation and
      collateralisation are predictive of outcome after thrombolytic therapy in acute
      ischaemic stroke. We carried out angiography and local intra-arterial (97) or
      systemic (14) thrombolysis within 6 h of the onset in patients with an ischaemic
      stroke in the territory of the internal carotid artery. Early ischaemic signs
      (EIS) on pretreatment CT and angiographic findings were classified and analysed
      in relation to clinical outcome at 3 months. A favourable outcome (Barthel index
      [BI]>/= 90) was found in 40% of patients with an occlusion of the middle cerebral
      artery trunk whereas intracranial occlusion of the internal carotid artery
      ("carotid T occlusion") was followed by death or severe disability (BI<50) in
      87%. Significant univariate predictors of favourable outcome were occlusion type
      ( P<0.01), recanalisation ( P<0.01) and collateralisation ( P<0.01). However,
      multivariate analysis revealed a significant relationship only between
      collateralisation and favourable outcome (odds ratio 5.9, 95% confidence interval
      1.3-26.7, P=0.02). EIS were not predictive in either case. Occlusion type and
      recanalisation, are related to outcome only if adequate collateralisation
      prevents infarction until recanalisation occurs.

PMID- 12525949
TI  - Coiling of saccular basilar trunk aneurysms.
AB  - We reviewed the selective endosaccular coiling of eight consecutive patients with
      saccular basilar trunk aneurysms, seven after subarachnoid haemorrhage (SAH). All
      aneurysms could be coiled in a mean procedure time of 61 min. There were no
      procedure-related complications, but one patient died of vasospasm following the
      SAH. The remaining seven had a good outcome, and five of seven aneurysms were
      completely occluded with a stable result on follow-up angiography. Compaction of
      the coils occurred in one very large aneurysm necessitating additional coiling.
      One patient with a giant, partially thrombosed aneurysm was coiled four times in
      a 3-year period to obtain a satisfactory anatomical result.

PMID- 12525950
TI  - Failure of stent-assisted endovascular treatment for ruptured dissecting
      aneurysms of the basilar artery.
AB  - We report two instructive cases of ruptured dissecting aneurysm of the basilar
      artery. Although stent-assisted endovascular treatment was successful, recurrent
      bleeding occurred 4 h after the procedure in one patient, and the other's basilar
      artery occluded 6 days after the procedure. These cases suggest that the high
      porosity of currently available stents may be insufficient to induce intraluminal
      thrombosis and merely stenting may fail to prevent bleeding, while postoperative
      anticoagulation alone may be inadequate to prevent occlusion of the stented
      vessel.

PMID- 12525951
TI  - Two-dimensional thick-slice MR digital subtraction angiography in the assessment
      of small to medium-size intracranial arteriovenous malformations.
AB  - Assessment of intracranial arteriovenous malformations (AVMs) by conventional
      catheter angiography carries risks; moreover, this invasive procedure is often
      repeated for follow-up. We investigated the clinical applicability of two
      dimensional thick-slice, contrast-enhanced magnetic resonance digital subtraction
      angiography (2D MRDSA) with high temporal resolution in the assessment of AVMs.
      We performed 78 2D MRDSA studies of treated or untreated small to medium-size
      AVMs on a 1.5 tesla imager. Two observers independently evaluated demonstration
      of nidus flow void on T2-weighted images and each component of the AVM on 2D
      MRDSA employing a three-point grading scale. In 55 patients with AVMs, the mean
      ratings of nidus flow voids, feeding vessels, nidi, draining vessels and early
      venous filling on MRI were 2.8, 2.4, 2.6, 2.8 and 2.8, respectively. sensitivity,
      specificity, positive and negative predictive values for an AVM using 2D MRDSA
      were 87, 100, 100 and 78%, respectively and for nidus flow voids on T2-weighted
      images 80, 91, 96 and 66%, respectively. 2D MRDSA can thus demonstrate
      haemodynamic features of AVMs. It can be employed as a less invasive, dynamic
      angiographic tool for follow-up of AVMs previously delineated by catheter
      angiography.

PMID- 12525952
TI  - Diffuse axonal injury: detection of changes in anisotropy of water diffusion by
      diffusion-weighted imaging.
AB  - Myelinated axons of white matter demonstrate prominent directional differences in
      water diffusion. We performed diffusion-weighted imaging on ten patients with
      head injury to explore the feasibility of using water diffusion anisotropy for
      quantitating diffuse axonal injury. We showed significant decrease in diffusion
      anisotropy indices in areas with or without signal abnormality on T2 and T2*
      weighted images. We conclude that the water diffusion anisotropy index a
      potentially useful, sensitive and quantitative way of diagnosing and assessing
      patients with diffuse axonal injury.

PMID- 12525953
TI  - Ischemic lesions related to cerebral angiography: Evaluation by diffusion
      weighted MR imaging.
AB  - We examined the incidence of ischemic lesions occurring after cerebral
      angiography by means of diffusion weighted MR imaging (DWI). Fifty patients were
      included in this study. Balloon occlusion tests of the internal carotid artery
      were performed in 9 of the 50 patients. DWI was performed on the same day as the
      cerebral angiography or on the following day. No new neurological deficits were
      found after cerebral angiography. However, 13 of the 50 cases revealed new
      ischemic lesions after cerebral angiography. The incidence of ischemic lesions
      was significantly different between patients who underwent balloon occlusion
      tests and patients who did not. The incidence of ischemic lesions was not
      influenced by the duration of the procedure, use of additional catheters, total
      amount of contrast material or the type of contrast material. The incidence of
      clinically silent ischemic lesions related to cerebral angiography is greater
      than the incidence of neurological complications. In patients who underwent
      occlusion tests of the internal carotid artery, the incidence of silent lesions
      was significantly higher than in patients who did not.

PMID- 12525954
TI  - Dynamic contrast-enhanced MRI: differentiating melanoma and renal carcinoma
      metastases from high-grade astrocytomas and other metastases.
AB  - We performed conventional and dynamic susceptibility-contrast MRI imaging in 38
      patients with brain tumours: 20 with metastases (breast carcinoma: two; renal
      carcinoma: five; colorectal carcinoma: one; lung carcinoma: seven; melanoma:
      five), and 18 with high-grade astrocytomas. We obtained cerebral blood volume
      (CBV) maps and calculated the relative CBV (rCBV) in different areas using the
      ratio between the CBV in the pathological area (CBVp) and in the contralateral
      white matter (CBVn). We calculated the maximum rCBV (rCBVmax) for each tumour and
      compared the mean rCBVmax in each group of tumours. The mean rCBV of melanoma
      metastases (5.35+/-2.32, range 3.14-9.23) and of renal carcinoma metastases
      (8.17+/-2.39, range 5.41-11.64) were significantly greater than those of high
      grade astrocytomas (2.61+/-1.17, range 1.3-5.0) ( P=0.002 and <0.001,
      respectively) and of lung carcinoma metastases (2.94+/-0.86, range 1.43-4.04) (
      P=0.003 and 0.002). There was no statistically significant difference between the
      mean rCBV of lung metastases and of high-grade astrocytomas ( P=0.59). Large,
      solitary, necrotic metastases can be indistinguishable from high-grade
      astrocytomas using conventional MRI. Demonstration of an elevated rCBV which may
      suggest a hypervascular lesion such as renal carcinoma or melanoma.

PMID- 12525955
TI  - Magnetic resonance diffusion-weighted images in Creutzfeldt-Jakob disease: case
      report.
AB  - We describe the diffusion-weighted MRI findings and follow-up in a case of
      autopsy-proven Creutzfeldt-Jakob disease that revealed abnormal hyperintensity in
      the cortex and basal ganglia.

PMID- 12525956
TI  - Rupture of the lateral ventricle secondary to a fourth ventricle tumour resulting
      in an indirect nontraumatic cerebrospinal fluid fistula.
AB  - We present a rare indirect nontraumatic cerebrospinal fluid (CSF) fistula
      secondary to a fourth ventricle ependymoma. The fistula resulted from rupture of
      the left temporal horn, distant from the tumour. The fistula was well
      demonstrated by MRI. High-resolution CT demonstrated a defect in the roof of the
      sphenoid sinus, but no leakage of CSF was seen on CT cisternography.

PMID- 12525957
TI  - The review of drug applications submitted to the European Medicines Evaluation
      Agency: frequently raised objections, and outcome.
AB  - OBJECTIVE: To study the issues raised during the review of drug applications
      submitted to the European Medicines Evaluation Agency for approval in the
      European Union and to identify important predictors of outcome. METHODS: All
      consecutive applications submitted since September 1997 and which had reached an
      outcome by May 2001 were included. The factors considered in this exploratory
      analysis were: year of submission, anatomical therapeutic chemical classification
      (ATC code), type of medicinal product (biopharmaceuticals vs. new chemical
      entities), and common "major objections" raised during the review. Predictors
      were identified using multivariate logistic regression on outcome (positive
      opinion vs. negative opinion or withdrawal). Examples have been provided to
      illustrate some of the weaknesses of the applications received, the types of
      objections raised by the reviewers, and the strategies used to address them.
      RESULTS: This series consisted of 111 successive applications for which the
      review had started between September 1997 and April 2000. It included 73 (66%)
      new chemical entities and 38 (34%) biopharmaceuticals, the most represented
      agents being anti-neoplastic and immunomodulating agents, and anti-infectives for
      systemic use, with 25 (22%), and 19 (17%) applications, respectively. Overall the
      proportion of drug applications that failed to reach a positive outcome was
      32/111 (29%). The most frequent major objections raised were those related to the
      safety database and to serious adverse events. These clinical safety objections
      were raised in 54 (48.6%) applications. Another frequent objection was the
      clinical efficacy objection on the lack of adequate randomised controlled trials,
      which was raised in 47 (42.3%) applications. This clinical efficacy objection was
      the only factor that was retained after multivariate selection (P<0.01). The odds
      of a positive outcome for an application lacking adequate randomised controlled
      trials were: 0.46 (95% confidence interval 0.29-0.71) times the odds of an
      application without this objection (P=0.0006). CONCLUSIONS: Despite the existence
      of various mechanisms that allow important deficiencies to be resolved, failure
      to establish clinical efficacy due to the lack of adequate randomised controlled
      trials remained problematic, leading to a high risk of rejection.

PMID- 12525958
TI  - Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in
      rats.
AB  - RATIONALE: Dopaminergic mechanisms are thought to be critically involved in
      reward-related processes and seeking behaviour. OBJECTIVE: To examine the
      involvement of dopamine in seeking behaviour supported by a natural reinforcer,
      food, and assess the role of D(2) and D(3) receptor subtypes in food-seeking,
      using an operant reinstatement procedure. METHODS: Wistar rats were subjected to
      a within-session extinction procedure. Experimental sessions consisted of a 15
      min rewarded period during which each right lever press delivered one food pellet
      and initiated a 10-s time out period (FR1:TO(10s)), followed by a 45-min
      extinction period during which responding was no longer rewarded. The reinstating
      effects of dopaminergic drugs, food priming, or the combination of both
      treatments, were investigated during spaced test sessions. In dose range studies,
      dopamine receptor ligands were administered 20 or 30 min into the test sessions.
      In interaction studies, antagonists were injected immediately before testing.
      Food priming consisted of two pellets non-contingently delivered 45 min into the
      test sessions. RESULTS: Well trained rats emitted many responses during the
      rewarded period but almost none during extinction. During the last 15 min of the
      test sessions, non-rewarded responding was reinstated by the D(2)/D(3) agonist,
      apomorphine (0.125-0.25 mg/kg, SC), and the D(3) preferring agonist, 7-OH-DPAT (2
      4 mg/kg, SC), but not by quinelorane (0.004-2 mg/kg, SC), another D(3) preferring
      agonist. In interaction studies, the D(2) preferring antagonist, raclopride (0.06
      0.125 mg/kg, IP), and the D(3) preferring antagonist, l-nafadotride (1 mg/kg,
      IP), counteracted the reinstating effect of apomorphine and 7-OH-DPAT. Pellets
      non-contingently delivered during extinction, reinstated modest, but significant,
      responding. Such food-primed food-seeking was altered by neither nafadotride
      (0.015-1 mg/kg, IP) nor the D(2)/D(3) antagonists, amisulpride (0.25-1 mg/kg, IP)
      or sulpiride (2-4 mg/kg, IP). Food- and apomorphine-induced response
      reinstatement were additive, and food-primed food-seeking behaviour was
      potentiated by 7-OH-DPAT (0.125-1 mg/kg, SC) and quinelorane (7.5-15 micro g/kg,
      SC). Such a potentiation was reversed by two D(2) antagonists, haloperidol (0.05
      mg/kg, IP) and raclopride (0.125 mg/kg, IP), but not by nafadotride (1 mg/kg, IP)
      and another D(3) preferring antagonist, S 33084 (0.25-2 mg/kg, SC). CONCLUSION:
      These results indicate that reinstatement of non-reinforced responding by non
      contingent food delivery and by dopamine agonists probably depend on different
      mechanisms. The properties of D(2)/D(3) receptor agonists, to reinstate food
      seeking at larger doses, and to potentiate food-primed response reinstatement at
      lower doses, are preferentially mediated by D(2) rather than by D(3) receptors.

PMID- 12525959
TI  - Attenuation of cocaine-seeking behaviour by the AMPA/kainate receptor antagonist
      CNQX in rats.
AB  - RATIONALE: It has been suggested previously that conditioned effects on drug
      seeking behaviour are in part mediated through glutamatergic neurotransmission.
      OBJECTIVES: To optimise a second-order schedule of IV cocaine reinforcement in
      Wistar rats and investigate the effects of the systemic AMPA/kainate receptor
      antagonist CNQX on cocaine-seeking behaviour under this schedule. METHODS: Free
      feeding Wistar rats were trained to respond for an IV cocaine infusion (0.25
      mg/infusion) under a FI15 min(FR7:S) schedule, whereby the completion of FR7
      responses led to the presentation of a conditioned stimulus (CS). After two 15
      min fixed intervals, rats were allowed to respond for cocaine under an FR4(FR7:S)
      second-order schedule for another 120 min. After acquisition of stable
      responding, the cocaine unit dose was increased to 0.50 mg/infusion. The effects
      of CNQX (0, 0.75, 1.5, and 3 mg/kg IP) on cocaine seeking were then examined
      using a within-subjects design. RESULTS: Increasing the cocaine unit dose
      increased responding during the first and second intervals, with a decrease in
      the latency to the first CS. CNQX decreased the number of cocaine responses in a
      dose-dependent manner during the first 15-min cocaine-free interval, but did not
      affect cocaine responding during either the second interval or the latter part of
      the session under the FR4(FR7:S) schedule. In the locomotor activity test,
      reductions in rearing were produced by higher CNQX doses than those that
      attenuated significantly responding during the first fixed interval. CONCLUSIONS:
      These results suggest that AMPA/kainate receptors are involved in mediation of
      cocaine-seeking behaviour controlled partly by cocaine-associated cues.

PMID- 12525960
TI  - Characterization of the pupil light reflex, electroretinogram and tonometric
      parameters in healthy rat eyes.
AB  - PURPOSE: To characterize the pupil light reflex (PLR), electroretinographic (ERG)
      and tonometric parameters in healthy rat eyes. METHODS: Brown Norway rats were
      used for experiments. The PLR was evaluated with a computerized pupillometer (n =
      27), ERGs were recorded simultaneously from both eyes (n = 27) and IOP was
      measured with a Tonopen (n = 15). RESULTS: The analysis of the PLR parameters
      confirmed that the consensual PLR had a significantly smaller amplitude (0.1-0.2
      mm; p = 0.03) and an increased latency time (p = 0.001) compared to the direct
      PLR. Electroretinography revealed an a-wave amplitude of 207.2 +/- 13 microV with
      a latency of 25.6 +/- 0.7 ms, and a b-wave 554.3 +/- 24.5 microV with a latency
      of 21.4 + 1.8 ms. The flicker ERG recording revealed amplitudes of 40.6 +/- 2.4
      microV. Tonometry measurements revealed that isoflurane, but not halothane,
      anesthesia suppressed the IOP (non-anesthetized: 25.3 +/- 1.0 mmHg; 1% halothane
      + 30% NO: 26.2 +/- 1.1 (p > 0.1); 1% isoflurane + 30% NO: 20.1 + 1.6 (p < 0.05)).
      CONCLUSIONS: Consensual PLR in rats has a relative deficit compared to the direct
      PLR. Isoflurane anesthesia has a suppressive effect on the IOP in healthy rat
      eyes.

PMID- 12525961
TI  - Extracellular matrix ligands promote RPE attachment to inner Bruch's membrane.
AB  - PURPOSE: To determine if resurfacing layers of human Bruch's membrane with
      extracellular matrix ligands increases adult human retinal pigment epithelium
      (RPE) attachment. METHODS: We removed successive layers of Bruch's membrane
      sequentially by mechanical or enzymatic means to expose the RPE basal lamina,
      inner collagen layer, and elastin layer. Each layer was coated with extracellular
      matrix proteins (4 microg/cm(2) laminin, 4 microg/cm(2) vitronectin, 20
      microg/cm(2) fibronectin, 20 microg/cm(2) collagen IV) for 2 hrs at 37 degrees C.
      First passage adult human RPE (15000 cells/6 mm explant) were plated onto coated
      or uncoated Bruch's membrane layers and RPE attachment was measured 18 hrs later.
      RESULTS: The reattachment rate to basal lamina derived from younger (age < 50)
      donors was higher than older (age >/= 70) donors (56.2 +/- 4.8% versus 46.7 +/-
      0.7% respectively; p < 0.05). Coating with laminin or collagen IV increased RPE
      attachment to older but not younger basal lamina. The reattachment rate to inner
      collagen derived from younger donors was higher than older donors (51.3 +/- 2.7%
      versus 37.4 +/- 1.7% respectively, p < 0.05). Coating with laminin, fibronectin
      or collagen IV increased RPE attachment to older but not younger inner collagen
      layer. Adding extracellular matrix ligands did not increase RPE attachment to
      elastin. CONCLUSIONS: RPE attachment is increased by adding ligands to the basal
      lamina or inner collagen layer but not to the elastin layer. This may be
      important if the elastin layer is exposed in AMD patients after submacular
      surgery.

PMID- 12525963
TI  - Time dependent effects of sympathetic denervation on aqueous humor dynamics and
      choroidal blood flow in rabbits.
AB  - PURPOSE: This study investigates the time-dependent effects of superior cervical
      ganglionectomy (SCGx) on aqueous humor dynamics and ocular blood flow in rabbits.
      METHODS: Measurements were made at various times between 24 hours and 12 months
      after SCGx. Intraocular pressure (IOP) was measured by pneumatonometry, aqueous
      flow by fluorophotometry and outflow facility by tonography. Uveoscleral outflow
      was determined by an intracameral tracer infusion technique and blood flow to the
      choroid was evaluated with fluorescent microspheres. Values in denervated eyes
      were compared with the contralateral, normally-innervated eyes using a paired
      Student's two-tailed t-test. RESULTS: At 24 hours after SCGx, IOP in denervated
      eyes was less than in normally-innervated eyes (14.6 +/- 0.8 vs 20.1 +/- 1.5
      mmHg, 27%, p < 0.002). At one month, IOPs were not different between eyes.
      Compared with normally-innervated eyes at 10-12 months, IOP in denervated eyes
      was greater (20.4 +/- 0.7 vs 17.2 +/- 0.9 mmHg, 19%, p < 0.001), outflow facility
      was less (0.15 +/- 0.02 vs 0.21 +/- 0.01 microl/min/mmHg, 29%, p < 0.01) and
      blood flow to the choroid was less (12.1 +/- 5.0 vs 16.2 +/- 6.0 ml/min/gm
      tissue, 25%, p < 0.05). Aqueous humor flow was not significantly altered by SCGx
      at any time. CONCLUSIONS: The reduction in IOP at 24 hours after SCGx was not due
      to any change in aqueous flow or uveoscleral outflow (current study) but rather
      to an increase in outflow facility (previous studies). At 10-12 months, IOP was
      elevated because outflow facility was significantly reduced. The reduction in
      choroidal blood flow at 10-12 months may have occurred because of the increased
      IOP.

PMID- 12525962
TI  - Non-preserved 1% lidocaine solution has less antibacterial properties than
      currently available anaesthetic eye-drops.
AB  - PURPOSE: Some anaesthetics inhibit bacterial growth, and thus may lead to low
      rates of positive cultures from bacterial keratitis. Antibacterial properties of
      lidocaine were compared with those of oxybuprocaine or tetracaine, either in
      current commercial eye lotions or in extemporaneous solutions. METHODS: Forty
      eight bacterial strains were used to determine the minimum inhibitory and
      bactericidal concentrations of four commercial eye lotions containing
      oxybuprocaine or tetracaine, of a non-ophthalmic 1% lidocaine commercial solution
      and of extemporaneously prepared solutions of oxybuprocaine, tetracaine,
      lidocaine and benzalkonium. RESULTS: Most strains had their growth inhibited by
      0.2% oxybuprocaine or 0.4% tetracaine, which corresponds to a 1/2 dilution of the
      commercial eye-drops. Bacterial growth was still observed with a 1% lidocaine
      solution. CONCLUSIONS: Currently available anaesthetic eye-drops that are used
      before corneal specimen collection may lead to false-negative bacterial cultures.
      Conversely, a non-preserved 1% lidocaine solution might be more appropriate in
      corneal specimen collection.

PMID- 12525964
TI  - The effect of corneal thickness and corneal curvature on pneumatonometer
      measurements.
AB  - PURPOSE: The purpose of this study was to investigate the influence of corneal
      topography and thickness on intraocular pressure (IOP) and pulse amplitude (PA)
      as measured using the Ocular Blood Flow Analyzer (OBFA) pneumatonometer (Paradigm
      Medical Industries, Utah, USA). METHODS: 47 university students volunteered for
      this cross-sectional study: mean age 20.4 yrs, range 18 to 28 yrs; 23 male, 24
      female. Only the measurements from the right eye of each participant were used.
      Central corneal thickness and mean corneal radius were measured using Scheimpflug
      biometry and corneal topographic imaging respectively. IOP and PA measurements
      were made with the OBFA pneumatonometer. Axial length was measured using A-scan
      ultrasound, due to its known correlation with these corneal parameters. Stepwise
      multiple regression analysis was used to identify those components that
      contributed significant variance to the independent variables of IOP and PA.
      RESULTS: The mean IOP and PA measurements were 13.1 (SD 3.3) mmHg and 3.0 (SD
      1.2) mmHg respectively. IOP measurements made with the OBFA pneumatonometer
      correlated significantly with central corneal thickness (r = +0.374, p = 0.010),
      such that a 10 microm change in CCT was equivalent to a 0.30 mmHg change in
      measured IOP. PA measurements correlated significantly with axial length (part
      correlate = -0.651, p < 0.001) and mean corneal radius (part correlate = +0.459,
      p < 0.001) but not corneal thickness. CONCLUSIONS: IOP measurements taken with
      the OBFA pneumatonometer are correlated with corneal thickness, but not axial
      length or corneal curvature. Conversely, PA measurements are unaffected by
      corneal thickness, but correlated with axial length and corneal radius. These
      parameters should be taken into consideration when interpreting IOP and PA
      measurements made with the OBFA pneumatonometer.

PMID- 12525965
TI  - Autoantibodies in glaucoma.

PMID- 12525966
TI  - Correlation between reading skills and different measurements of convergence
      amplitude.
AB  - PURPOSE: To find correlations between convergence amplitude and reading ability,
      as assessed in various methods. METHODS: Convergence of 66 children aged 8-10
      years was evaluated using 1) Non-accommodative target at near and distance; 2) A
      near computerized stereogram; and 3) Measurement of near point of convergence
      (NPC). Reading ability was examined by: 1) a reading comprehension test and 2)
      the Developmental Eye Movement Test (DEM), which evaluates saccadic speed and
      accuracy. RESULTS: Convergence amplitudes on a distant target and on a near
      stereogram were correlated with the DEM score (P = 0.005/0.02, r = -0.38/-0.32
      and P < 0.001/0.002, r = -0.53/-0.53 for break/recovery respectively), while NPC
      and convergence on a near non-accommodative target did not. Reading comprehension
      test score was not correlated with any of the convergence measurements.
      CONCLUSIONS: Convergence amplitude measured while accommodation is controlled was
      correlated with the DEM score, which evaluates saccadic speed and accuracy.
      Further study to evaluate whether improvement in vergence control improves DEM
      scores is needed.

PMID- 12525967
TI  - Experimental macular edema induced by macular venule occlusion in monkey.
AB  - PURPOSE: Visual prognosis after retinal vein occlusion varies, because it may be
      affected by macular edema or an avascular area. The mechanism describing how
      macular edema and avascular areas occur, however, has not been clearly
      understood. We induced macular edema in cynomolgus monkeys by occluding macular
      venules to evaluate the retinal microcirculation. METHODS: We produced venous
      occlusion by applying dye laser in three cynomolgus monkeys. Macular edema was
      examined by slit lamp biomicroscopy and optical coherence tomography. Acridine
      orange leukocyte fluorography (AOLF) and fluorescein angiography were performed
      to study blood flow and vascular leakage before and after laser application.
      RESULTS: We observed three types of retinal changes in the macular area: (1)
      macular edema did not develop; (2) macular edema developed, but improved with
      avascular area formation; (3) macular edema developed, but disappeared without
      avascular area formation. Under physiological conditions, observation revealed
      that leukocytes flowed from arterioles into either superior or inferior venules.
      When macular edema did not develop, most leukocytes from arterioles escaped into
      the adjacent non-occluded venules. In contrast, when macular edema occurred,
      leukocyte flow became stagnated. Macular edema developed when capillary leakage
      was observed from venules and subsequently arterioles, but disappeared when an
      avascular area was formed by arteriole occlusion. CONCLUSIONS: We demonstrated
      that experimental macular edema could be induced by macular venule occlusion in
      monkeys. According to our observation by AOLF, whether macular edema is induced
      or not depends on the function of collateral routes of the remaining non-occluded
      venules. We could consider that a gradual increase in intravascular pressure was
      associated with the avascular area formation.

PMID- 12525968
TI  - Wavelet analysis for corneal topographic surface characterization.
AB  - PURPOSE: To demonstrate a mathematical method for multiscalar decomposition of
      discrete corneal topography height data into a space-scale space using wavelet
      analysis techniques, and to demonstrate the clinical applicability of these
      computations in the postkeratoplasty cornea. METHODS: Fifty patients with either
      Fuchs' dystrophy (n = 20) or keratoconus (n = 30) were seen preoperatively, at 3
      months, at 1 year (before suture removal) and again at 19 +/- 3 months (after
      suture removal) following nonmechanical trephination with an excimer laser for
      penetrating keratoplasty. Patients were assessed using corneal topography
      analysis (TMS-1), subjective refraction, and best-corrected visual acuity (VA) at
      each interval. Two-dimensional biorthogonal wavelets with the order 6.8 at the
      scales j = 1-4 revealed the following parameters: root-mean square (RMSDEV) and
      mean absolute (MEANDEV) deviation and maximum absolute height of the peaks or
      pitches (MAXPEAK) relative to the reference surface specified with the
      approximation component of scale j = 4. RMSDEV was correlated with the VA at
      various follow-up intervals. The multiscalar basis components: roughness,
      waviness and form were separated and recovered from the wavelet soft thresholding
      techniques. Peaks and pits within the three-dimensional corneal surface
      topography were detected and localized using the wavelet hard thresholding
      techniques. RESULTS: In patients with keratoconus, the RMSDEV and the MEANDEV
      increased from 4.31 +/- 1.25/5.98 +/- 1.88 microm preoperatively to the 3 months
      follow-up (4.98 +/- 1.41/6.92 +/- 2.16 microm) and thereafter decreased
      continuously to the end of the follow-up (1.87 +/- 0.63/2.63 +/- 1.07 microm),
      whereas in Fuchs' dystrophy the respective values started at a higher
      preoperative level (6.36 +/- 1.24/7.20 +/- 2.64 microm) and decreased
      continuously over time (2.73 +/- 1.10/3.71 +/- 1.05 microm after suture removal).
      In the keratoconus group, the MAXPEAK was increased at the 3 month postoperative
      exam (8.78 +/- 2.29 microm) when compared to the preoperative value (6.55 +/-
      2.56 microm); however, it decreased again and returned to the preoperative level
      after one year (6.34 +/- 2.12 microm after suture removal). In Fuchs' dystrophy,
      the MAXPEAK was unchanged preoperatively (8.26 +/- 2.83 microm) to the 3 months
      follow-up, but decreased continuously to the end of the follow-up period (4.57 +/
      1.36 microm). The RMSDEV was significantly lower in keratoconus than in Fuchs'
      dystrophy preoperatively (P = 0.01) and after suture removal (P = 0.005) and
      correlated inversely with VA preoperatively (R = -0.53, P = 0.04/R = -0.69, P =
      0.02), at the 1 year exam (R = -0.61, P = 0.02/R = -0.52, P = 0.05) and after
      suture removal (R = -0.73, P = 0.01/R = -0.66, P = 0.025) in keratoconus/Fuchs'
      dystrophy. CONCLUSIONS: The use of wavelet analysis can provide significant
      clinical information by separating the raw data into the parameters: "roughness",
      "waviness", "form" and various multiscalar peaks and pits. The RMSDEV, a
      quantitative measure for corneal irregularity, can be used as a new approach for
      the prediction of potential visual acuity after penetrating keratoplasty. The
      decomposition of the surface elevation into fundamental components is crucial for
      a subsequent mathematically based extraction of clinical parameters or for
      topography-based flying-spot ablation of irregular corneal astigmatism.

PMID- 12525969
TI  - Three-axis ellipsoidal fitting of videokeratoscopic height data after penetrating
      keratoplasty.
AB  - PURPOSE: After penetrating keratoplasty corneal topography tends to be irregular
      and the fitting of spectacle glasses or contact lenses may be difficult. The
      purpose of this study was to demonstrate a mathematical method for approximation
      of discrete corneal topography height data with an ellipsoid for better
      appreciation of the clinical outcome after PK. PATIENTS AND METHODS: In 50 eyes
      (30 keratoconus, 20 Fuchs' dystrophy) penetrating keratoplasty was performed
      using nonmechanical trephination with the excimer laser 193 nm. Main outcome
      measures were objective corneal astigmatism (regular keratometry, corneal
      topography (TMS-1)), subjective refraction and best-corrected visual acuity (VA)
      in a fixed postoperative gate 3 and 12 month postoperatively and after suture
      removal. An approximation algorithm was applied for fitting a general ellipsoidal
      surface (not rotationally symmetric) to raw corneal topography height data. A set
      of parameters (meridional power, axis and asphericity) were calculated. The root
      mean square error (RMS) was determined between raw topography power data and the
      ellipsoidal model surface within an apical distance of 3 mm. The cylinder of
      subjective refraction was correlated with the keratometric readings, the
      Simulated Keratometry (SimK) of the topography system and the respective
      parameters of the model surface. RESULTS: The amount of the SimK cylinder yielded
      higher values than keratometry and the ellipsoidal fit; subjective refraction
      yielded the lowest value at each follow-up interval. The ellipsoidal fit showed
      the best correlation to the refractive cylinder at all follow-up stages (p = 0.04
      at 3, p = 0.01 at 12 months and p = 0.002 after suture removal). The axis of the
      best ellipsoidal fit showed a significant correlation with the axis of the
      refractive cylinder at all follow-up intervals (p = 0.02 at 3 months, p = 0.01
      before suture removal and p = 0.002 after suture removal). The axis of the
      keratometric cylinder showed a mild correlation at all follow-up examinations (p
      = 0.05 at 3 months, p = 0.02 before suture removal and p = 0.04 after suture).
      The cylinder of the topographic modeling system, however, showed a significant
      correlation with the refractive cylinder axis only after suture removal (p =
      0.04). The paracentral corneal power of SimK (45.9D at 3 months, 44.4D at 12
      months and 43.0D after suture removal) exceeded the respective values of
      conventional keratometry (43.1D at 3 months, 42.9D at 12 months and 41.7D after
      suture removal) and the ellipsoidal fit (43.3D at 3 months, 43.0D at 12 months
      and 41.8D after suture removal). The corneal asphericity from the ellipsoidal fit
      reached an approximately spherical shape in radial direction (A = 1.0) in the
      initial time period after penetrating keratoplasty, remained stable before suture
      removal and decreased significantly (p = 0.02) to a final value of A = 0.86
      indicating a (normal) prolate shape of the cornea. The approximation error
      between the raw corneal topography height data and the best ellipsoidal fit model
      surface was nearly unchanged before suture removal (1.8 +/- 0.7 microm at 3
      months and 1.9 +/- 1.1 microm at 12 months, p = 0.30) and decreased significantly
      to the examination after suture removal (0.9 +/- 0.5 microm, p = 0.01).
      CONCLUSIONS: The approximation of corneal topography height data with an
      ellipsoidal model surface renders reconstruction of clinically relevant corneal
      topography parameters including corneal asphericity. Even in markedly irregular
      corneal surfaces, such as after PK, the correlation of amount/axis of refractive
      cylinder with the model surface parameters is more accurate than with respective
      SimK values of corneal topography analysis.

PMID- 12525970
TI  - Changes in connexin43 in early ocular surface development.
AB  - PURPOSE: In the limbo-corneal epithelium the stem and early precursor epithelial
      cell pool is confined to the limbal rim. Among the features associated with this
      spatial segregation is the general paucity of connexin43 (Cx43) within the limbal
      basal cell population and its complete absence in resident stem cells. The limbo
      corneal epithelial lineage derives from a Cx43-positive (Cx43+) embryonic outer
      ectoderm. Accordingly, as a means of identifying the process through which limbal
      cell phenotypes emerge, we investigated the expression of Cx43 in the ocular
      surface of embryonic rats. METHODS: Ocular surface expression of Cx43 or K12 was
      determined in cryostat sections of rat embryos and eyes using immunohistological
      methods. RESULTS: Changes in Cx43 expression revealed the early phenotypic
      divergence of three main epithelial cell phenotypes of the ocular surface. An
      analysis of the level and distribution pattern of Cx43 puncta lead to the
      identification of two distinct domains by embryonic day 10 (E10), a stage that
      occurs soon after formation of the lens vesicle. Additionally, at E12, ectodermal
      cells directly adjacent to the edges of the developing retina no longer express
      connexin. A comparison of anatomical and expression changes throughout embryonic
      development demonstrated that the two early zones represent the rudiments for the
      epithelia of the central cornea and conjunctiva, respectively, and that the
      isolated Cx43-negative (Cx43-) cells represent the precursors of the basal and,
      putatively, stem cells of the limbal epithelium. CONCLUSIONS: Changes in Cx43
      expression revealed that the phenotypic divergence of ocular surface epithelial
      cells and the generation of limbo-corneal stem cell precursors takes place at a
      very early stage in ocular development, ahead of the establishment of any
      identifiable anatomical or differentiation features for these domains.

PMID- 12525971
TI  - Ultrastructural characterization of developmental and degenerative vitreo-retinal
      changes in the eyes of transgenic mice with a deletion mutation in type II
      collagen gene.
AB  - PURPOSE: Molecular genetic analyses have clearly associated vitreoretinal
      degeneration with mutations in the type II collagen gene, but lack of
      experimental models has prevented systematic analyses of the occurrence of
      phenotypic changes and of the pathogenetic mechanisms involved. The present study
      is a detailed morphological and ultrastructural analysis of the vitreoretinal
      consequences of a small deletion mutation in the type II collagen gene. METHODS:
      The eyes of Del1 mice carrying six copies of pro alpha1(II) collagen transgene
      with a small deletion mutation were analyzed during embryonic development,
      postnatal growth and aging using their nontransgenic littermates as controls.
      Tissue samples were processed for light and electron microscopy for morphological
      and ultrastructural analyses. Transcription of pro alpha1(II) collagen gene was
      localized by in situ hybridization, and type II collagen was detected by
      immunohistochemistry. RESULTS: In this mouse model most components of the eye are
      ultrastructurally unaltered. However, the transgenes caused a dose-dependent
      dominant negative effect seen as a reduced number of type II collagen fibrils in
      the vitreous. In concert with this, dose-dependent accumulation of amorphous
      material was observed in the dilated rough endoplasmic reticulum of cells
      responsible for the production of type II collagen molecules. In mice homozygous
      for the transgene locus, the vitreoretinal degenerative lesions appeared already
      during late embryonic development. In mice heterozygous for the locus, such
      changes were milder and appeared only during postnatal growth and progressed
      gradually upon aging. CONCLUSIONS: The observed ultrastructural changes suggest
      that defective structure and function of collagen fibrils in Del1 mice result
      from a partial block in the post-translational processing and secretion of the
      mutated procollagen chains, and partly from secretion of mutated procollagen
      molecules which interfere with normal fibrillogenesis.

PMID- 12525972
TI  - Chemokine gene expression in iris-ciliary body during experimental autoimmune
      uveoretinitis.
AB  - PURPOSE: To evaluate, through differential gene expression of chemokines in iris
      ciliary body (I/CB), the extent to which leukocyte recruitment to the ocular
      anterior segment participates in the pathogenesis of experimental autoimmune
      uveoretinitis (EAU) in mice. METHODS: B10.A mice were immunized with 50 microg of
      interphotoreceptor retinoid binding protein (IRBP) mixed with complete Freund's
      adjuvant. Aqueous humor (AqH) was collected at 0, 11, 17, and 28 days and assayed
      for leukocyte content and protein levels. Enucleated eyes were subjected to
      histologic analysis. Chemokine gene expression in I/CB was determined at these
      same time points by a multiprobe ribonuclease protection assay (RPA) system.
      RESULTS: Inflammation was detected in the anterior chamber (AC) at 11 days and
      leukocyte recruitment continued thereafter. Polymorphonuclear neutrophils (PMN)
      were the predominant cell type in the AC, whereas macrophages/monocytes and
      lymphocytes were predominant in the retina/subretinal space at 17 days. Peak gene
      expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2
      and interferon-gamma-inducible protein of 10 kd (IP-10) was detected in I/CB on
      day 11, whereas peak expression of RANTES and eotaxin was observed at 17 days.
      CONCLUSIONS: Early I/CB peak expression of mRNA for MIP-2 followed by PMN
      recruitment into the AC, suggests that PMN may play an important role in EAU
      pathogenesis.

PMID- 12525973
TI  - A new method and device to induce transient retinal ischemia in the rat.
AB  - PURPOSE: To describe and characterize a novel, non-invasive method to induce
      retinal ischemia in the rat. METHODS: Retinal ischemia was produced by applying a
      compression force with a suture thread anchored about 2mm behind the limbus of
      the eye in order to increase intraocular pressure and reduce ocular blood flow.
      Both ends of the suture thread were connected to weights via a pulley system. The
      effect of various weights (20, 25, or 35 g) on retinal damage was tested in
      animals of different body weights (350 and 574 g). Scotopic ERG measurements and
      histological sections of retinal tissue were used to evaluate possible functional
      and morphological changes to the retina as a consequence of ischemia followed by
      reperfusion. RESULTS: Retinal ischemia was achieved by this method with good
      reproducibility. The degree of retinal damage, as quantified by ERG measurement,
      correlated with the amount of weight connected to the suture thread. Seven days
      after 60 minutes of retinal ischemia, the amplitudes of A- and B-waves of eyes
      compressed with a 20 g weight were 84 +/- 11% and 86 +/- 16% (mean +/- SEM, n =
      4, amplitudes before ischemia defined 100%), respectively. The A- and B-wave
      amplitudes of eyes compressed with 25 g were 69 +/- 7% and 76 +/- 6% (n = 11),
      respectively. A 35 g treatment produced A- and B-wave amplitudes of 55 +/- 3.9%
      and 52 +/- 4% (n = 35), respectively. There was no significant difference in the
      level of ischemic damage in the two groups of animals with different body weights
      evaluated in this study. At two weeks after 60-minute retinal ischemia, there was
      a significant decrease (by 31.1%) in the cell density in the retinal ganglion
      cell layer. CONCLUSIONS: The pulley method is an easy, non-invasive, and highly
      reproducible technique for inducing retinal ischemia in rats. This procedure may
      provide a useful animal model of ischemic retinopathy.

PMID- 12525974
TI  - Effective transfection of a cis element "decoy" of the nuclear factor-kappaB
      binding site into the experimental choroidal neovascularization.
AB  - PURPOSE: To evaluate the efficacy of the gene transfer of a double-stranded
      phosphorothioate oligonucleotides (ODNs), called a "decoy", against the NF-kappaB
      binding site into cells of an experimentally-induced choroidal
      neovascularization. METHODS: FITC-labeled decoy was injected into the subretinal
      space of rat eyes by the HVJ-liposome delivery system, and 3 days later,
      choroidal neovascularization was induced by laser photocoagulation. The eyes were
      removed and the transfected cells were detected by fluorescence microscopy and
      also detected by immunohistochemistry. The degree of neovascularization was
      evaluated by fluorescein angiography. RESULTS: The decoy was transfected into the
      retinal pigment epithelial (RPE) cells, inner and outer segment of the
      photoreceptors at 3 days after the injection. When choroidal neovascularization
      was induced, highly effective transfection of the decoy was observed 3 to 14 days
      after photocoagulation, after which the level decreased. Decoys were transfected
      into the RPE cells and macrophages in the choroidal neovascularization. The eyes
      transfected with NF-kappaB decoy showed a weaker leakage in fluorescein
      angiograms than that of the control eyes transfected with scrambled decoy.
      CONCLUSIONS: A decoy can be transfected into retinal cells and cells within a
      choroidal neovascularization by the HVJ-liposome method. The transferred NF
      kappaB decoy reduced the degree of choroidal neovascularization. Decoy targeted
      against NF-kappaB may be considered as a potential therapy for
      neovascularization.

PMID- 12525975
TI  - [Management of dose and quality in digital radiography].

PMID- 12525976
TI  - [Radiofrequency ablation: basic principles, techniques and challenges].
AB  - Radiofrequency (RF) thermal ablation is a promising and rapidly evolving
      technique for the minimal invasive treatment of liver malignancies. Until a few
      years ago, conventional RF treatment performed with a single monopolar electrode
      produced thermal necrosis lesions not exceeding 1.6 cm in diameter. Substantial
      improvements in the RF technique included the development of high-power
      generators (up to 250 watts) combined with open-perfused electrodes, internally
      cooled-tip electrodes or expandable electrode needles, capable of ablating an
      area of over 5 cm in diameter. Moreover, angiographically and pharmacologically
      assisted strategies were introduced for expanding the volume of RF-induced
      coagulation necrosis. This article presents a synopsis of current RF techniques
      and reviews the basic principles of RF ablation with the goal of providing
      guidance for optimal results.

PMID- 12525977
TI  - Background suppression using magnetization preparation for contrast-enhanced 3D
      MR angiography of the pelvic and lower leg arteries.
AB  - PURPOSE: To develop and evaluate non-slab-selective magnetization preparation in
      contrast-enhanced 3D-MR angiography. METHODS: An ultrafast spoiled mr angiography
      sequence (FLASH) with non-selective inversion prepulses for background
      suppression was implemented on a 1.5 T MR system. In 11 patients gadobenate
      dimeglumine-enhanced mr-angiography of the pelvic and lower leg arteries was
      performed using the AngioSURF device. Source data was evaluated for contrast-to
      noise-ratio, image quality and the extent of background suppression. RESULTS:
      Background suppression and selective vessel contrast was excellent in all
      vascular levels. The mr protocol was comfortable and easy-to-handle. Abandonment
      of precontrast-series acquisition simplified the examination procedure markedly.
      CONCLUSIONS: Magnetization preparation provides efficient suppression of the
      background signal in contrast-enhanced 3D mr angiography of the pelvic and lower
      leg arteries. Since no subtraction technique is needed, moving-bed and whole body
      MRA-protocols can be simplified significantly.

PMID- 12525978
TI  - [Image quality and exposure dose in digital projection radiography].
AB  - PURPOSE: Comparison of the imaging capabilities of storage phosphor (computed)
      radiography and flat plate radiography with conventional film-screen radiography
      to find new strategies for quality and dose management, i. e., optimizing imaging
      quality and dose depending on the imaging method and clinical situation.
      MATERIALS AND METHODS: Images of a CDRAD-phantom, hand-phantom, abdomen-phantom
      and chest-phantom obtained with different exposure voltages (50 kV, 73 kV, 109
      kV) and different speeds (200, 400, 800, 1600) were processed with various
      digital systems (flat plate detector: Digital Diagnost [Philips]; storage
      phosphors: ADC-70 [Agfa], ADC-Solo [Agfa], FCR XG 1 [Fuji]) and a conventional
      film-screen system (HT100G/ Ortho Regular [Agfa]). RESULTS: The evaluation of
      CDRAD images found the flat plate detector system to have the highest contrast
      detectability for all dose levels, followed by the FCR XG 1, ADC-Solo and ADC-70
      systems. Comparison of the organ-phantom images found the flat plate detector
      system to be equal to film-screen radiography and especially to storage phosphor
      systems even for low exposure doses. CONCLUSIONS: Flat plate radiography systems
      demonstrate the highest potential for high image quality when reducing the
      exposure dose. Depending on the system generation, the storage phosphor systems
      also show an improved image quality, but the possibility of a dose reduction is
      limited in comparison with the flat plate detector system.

PMID- 12525979
TI  - [Chest radiography: ROC phantom study of four different digital systems and one
      conventional radiographic system].
AB  - PURPOSE: To compare the diagnostic quality of five different radiographic systems
      used in chest radiography for visualization of differently configured, clinically
      relevant pathologic pulmonary structures. MATERIALS AND METHODS: Four digital
      detector systems using as detection unit a CsI/aSi-based flat panel detector, a
      transparent imaging plate, a selenium detector and a conventional storage
      phosphor plate were analyzed for this study, as well as an asymmetrical film
      screen system. The analyzed imaging material consisted of radiographs of an
      anthropomorphic chest-phantom with superimposed simulated pulmonary structures.
      The images were evaluated for different pathologic structures by a newly
      developed multiple structure ROC (ms-ROC). RESULTS: The performance of each
      system was found to have a strong structure-related variability. The flat panel
      detector system had the best overall performance. The theoretical advantage of
      the 4k-matrix of the transparent imaging plate over the 3k-matrix of the flat
      panel detector was only confirmed for reticular structures. CONCLUSIONS: In
      addition to comparing the image quality of the different systems, this study
      shows that the performance of a radiographic system depends on the structure to
      be analyzed. The modified ROC (ms-ROC) provides valid results with less effort.

PMID- 12525980
TI  - [Quality control of outpatient imaging examinations in North Rhine-Westphalia,
      part I].
AB  - PURPOSE: In the state of North-Rhine Westphalia (NRW), Germany, a survey was
      conducted on radiologic examinations ordered by general practitioners (GPs). Part
      I of this study aims to collect characteristic epidemiological data and to assess
      structural quality. MATERIALS AND METHODS: All GPs in NRW were asked to
      cooperate. Participating GPs filled out a questionnaire for each patient. The
      patients recorded the symptoms prompting the imaging examinations. The
      radiologists or other physicians performing the examinations were asked to
      provide the images and written reports and to complete a questionnaire. Two
      university radiologists documented the pertinent test data from the submitted
      images and written records. Independently of each other, five university
      radiologists anonymously reviewed the image quality of each examination using
      structured questionnaires. RESULTS: A total of 920 patients gave their informed
      consent and participated. Questionnaires from 787 patients, 852 GPs and 611
      radiologists or other interpreting physicians as well as the complete survey data
      from 530 examinations were available. Of 1503 examinations, conventional
      radiography made up 52 %, sonography 17 %, computed tomography (CT) 13 % and
      magnetic resonance imaging (MRI) 5 %. Most indications involved the
      musculoskeletal (37 %) and respiratory systems (24 %). Physicians without board
      certification in radiology interpreted 1 % of the CT examinations, 26 % of the
      radiographic examinations and 71 % of the sonographic examinations. Of the 174
      self-referrals, 1 % involved CT, 33 % conventional radiography and 66 %
      sonography. Written reports were available for 95 % of all 469 examinations
      performed by radiologists and 74 % of all 127 examinations conducted by non
      radiologists. Only 44 % of the 23 sonographic studies were self-referrals by the
      patient's GP. On average, the radiographic techniques were acceptable in terms of
      diagnostic information and radiation hygiene. Conventional radiographs were
      better exposed when obtained by radiologists than by non-radiologists (p =
      0.038). The delineation of anatomical structures was rated as good to acceptable
      for MRI, CT and conventional radiography, while the image quality was rated as
      diagnostically insufficient for sonography (p < 0.0001). The image quality of
      radiographic and sonographic examinations performed by radiologists was superior
      in comparison to examinations performed by physicians without board certification
      in radiology (p < 0.0001). CONCLUSION: Examination technique and imaging quality
      of MRI, CT and conventional radiography performed on outpatients were in an
      acceptable diagnostic range, whereas the quality of sonography was inadequate.

PMID- 12525981
TI  - [MR-imaging: quality assessment in patient care, education and research].

PMID- 12525982
TI  - [Prognostic value of pretreatment CT regarding local control in oropharyngeal
      cancer after primary surgical resection].
AB  - PURPOSE: To evaluate the prognostic implication of tumor infiltration and volume
      in primarily operated oropharyngeal carcinomas. MATERIAL AND METHODS: In 80
      patients with oropharyngeal squamous cell carcinomas (pT 1 = 22, pT 2 = 30, pT 3
      = 19 and pT 4 = 9), the tumor volume was measured by pretreatment CT and the
      extent of tumor infiltration determined by postoperative histologic examination.
      All patients were followed clinically for local tumor recurrence for at least two
      years after therapy. The statistical analysis consisted of chi 2 and U tests.
      RESULTS: The local control rate was 79 % (63/80). Of all evaluated anatomic
      structures, only midline crossing correlated significantly with local recurrence
      (p = 0.06). No correlation of tumor volume (p = 0.19) or T stage (p = 0.60) with
      the local recurrence rate was found. CONCLUSION: After primary surgery,
      oropharyngeal carcinomas with midline crossing have an increased risk of local
      recurrence, whereas the tumor volume only has a minor impact on the recurrence
      rate. This is in contrast to laryngeal or hypopharyngeal carcinomas.

PMID- 12525983
TI  - [Topography of the inferior alveolar nerve in relation to cystic processes of the
      mandible in dental MRI].
AB  - PURPOSE: Cystic processes are changing the course of the inferior alveolar nerve
      in the mandible. This study evaluates the possibility of demonstrating the
      relationship between space-occupying processes and the course of the
      neurovascular bundle. MATERIALS AND METHODS: Thirteen patients with cystic
      processes in the mandible (9 keratocystic lesions, 1 eosinophilic granuloma, 1
      plasmocytoma, 2 adamantinomas) were examined by MRI (1.5-T magnet, 8-cm surface
      coil, PD-gradient-echo-sequences in sagittal and coronal orientation, without
      enhancement) and the results retrospectively evaluated. RESULTS: The entire
      course of the nerve could be delineated in all patients. In six patients with
      minor cystic processes, the nerve was identified in both sagittal and coronal
      orientation. In seven patients with major cystic lesions, only parts of the nerve
      were detected in either image orientation, but the nerve could be visualized in
      its entire length by evaluating coronal and sagittal images side by side.
      CONCLUSION: It is possible to delineate the inferior alveolar nerve in its
      entirety along pathologic mandibular lesions. For large cystic lesions, this
      requires the evaluation of both coronal and sagittal sections of multidirectional
      MRI.

PMID- 12525984
TI  - [Comparison of the reliability of subjective evaluation and quantitative
      measurements of MR signal intensity in inflammations of the intratemporal facial
      nerve].
AB  - PURPOSE: To compare in a single-blind study the reliability of quantitative
      measurements and subjective evaluations of contrast enhancement of the facial
      nerve in patients with idiopathic facial paralysis. MATERIALS AND METHODS:
      Magnetic resonance images with a 0.7 mm slice thickness (surface coil) were
      obtained in patients with idiopathic facial paralysis before and after
      administration of Gd-DTPA, 0.1 mmol/kg. The five intratemporal segments of the
      facial nerve were quantitatively measured and subjectively assessed by five
      radiologists as to the degree of enhancement. The results were compared as to the
      reliability of both methods. RESULTS: Using the quantitative measuring method,
      175 measurements were calculated from a total of 350 regions of interest. At all
      35 measured sites, the five quantitative measurements produced identical results.
      In contrast, the subjective assessment of the five radiologists arrived at a
      majority consensus in only 16 sites. A complete agreement was not reached for any
      measured site. CONCLUSION: The measured quantitative increase in signal intensity
      after administration of contrast medium is more reliable than subjective
      assessment. The quantitative method enables reproducible signal intensity
      measurements even for different window settings and can be easily and swiftly
      performed at the workstation.

PMID- 12525985
TI  - [31P-MR spectroscopy of the brain in patients with anorexia nervosa:
      characteristic differences in the spectra between patients and healthy control
      subjects].
AB  - PURPOSE: To investigate whether 31 P-MR spectroscopy can detect reduced
      concentrations of high-energy phosphates, like PCr and NTP, caused by decreased
      metabolic activity in the brain of patients with anorexia nervosa (AN) and,
      furthermore, whether any impairment of the cerebral membrane metabolism can be
      derived from the spectra. MATERIAL AND METHODS: 10 female patients, age range 12 
      20 years and mean BMI (body mass index) of 14.8 +/- 1.6 kg/m 2, with clinically
      diagnosed AN (ICD-10, F50.0) and 10 healthy control subjects, age range 12 - 21
      years and mean BMI 19.0 +/- 2.1 kg/m 2, without nutritional disturbances: were
      investigated. 31P-MR spectroscopy was performed with a 1.5 T MRI unit using
      single volume selection in the frontal/prefrontal region of brain. Relative
      metabolic concentrations were quantified by normalizing the peak areas of the
      metabolites with the total area of the complete phosphorous spectrum, P tot, as
      well as with the peak area of beta-NTP. RESULTS: Significant differences between
      the two groups were observed for the metabolic ratios PDE/P tot, PDE/beta-NTP and
      alpha-NTP/P tot which were lower in the patient group except for alpha-NTP/P tot.
      These ratios also revealed a statistically significant correlation with the BMI
      (r PDE/Ptot = 0.747, r PDE/beta-NTP = 0.57, r alpha-NTP/Ptot = -0.56; p </= 0.1).
      Reduced relative concentrations of PCr/P tot, beta-NTP/P tot or Pi/P tot were not
      encountered. CONCLUSION: The lowered PDE/P tot ratio for patients with AN and its
      correlation with BMI suggests that decreased BMI induces compositional changes of
      the phospholipids in the brain, which decrease the fraction of mobile
      phospholipids.

PMID- 12525986
TI  - [Quantification of cardiac function with multislice spiral CT using retrospective
      EKG-gating: comparison with MRI].
AB  - PURPOSE: To quantify left ventricular function derived from retrospectively ECG
      gated multislice spiral CT (MSCT) data sets in comparison to MRI. MATERIALS AND
      METHODS: In 16 patients (14 males, 2 females, mean age 56.8 +/- 11.5 years),
      retrospectively ECG-gated MSCT angiography of the coronary arteries and breath
      hold steady state free precession cine MRI were performed. From MSCT data-sets,
      20 axial image series were reconstructed every 5 % of the RR interval.
      Multiplanar images were reformatted in the short axis orientation from axial
      images. End-systolic and end-diastolic images were selected. From these images
      end-systolic volume (ESV), end-diastolic volume (EDV) and stroke volume (SV) as
      well as the ejection fraction (EF) and myocardial mass (MM) were determined using
      the Simpson's method and compared with MRI. Furthermore, image quality was
      assessed for both imaging modalities using a four point grading scale. RESULTS:
      All parameters were found to have an excellent correlation between MSCT and MRI
      data (Pearson's correlation coefficient 0.95 - 0.99), without clinically relevant
      differences between both modalities. On average, the difference between both
      methods was 0.5 ml for ESV, 0.8 ml for EDV, 1.3 ml for SV, 0.9 % for EF and 2.3 g
      for MM. Image quality was slightly better for MRI (1.5 +/- 0.65) than for MSCT
      (1.64 +/- 0.74). CONCLUSION: Retrospectively ECG-gated MSCT angiography can not
      only visualize the coronary arteries but also enables precise quantification of
      the left ventricular function from the same MSCT data set.

PMID- 12525987
TI  - [Visualization of pulmonary vein stenosis after radio frequency ablation for
      treatment of atrial fibrillation using multidetector computed tomography with
      retrospective gating].
AB  - PURPOSE: With the number of radio frequency ablations (RFA) for treatment of
      chronic atrial fibrillation increasing, the diagnostic evaluation for RFA
      associated pulmonary vein stenosis is getting more important. This study
      investigates the feasibility of the visualization of pulmonary vein stenosis
      using non-invasive multidetector computed tomography. MATERIALS AND METHODS:
      Twenty-eight patients were examined following RFA-treatment. A 4-slice (20
      patients) and a 16-slice (8 patients) multidetector CT scanner (SOMATOM Volume
      Zoom and Sensation 16, Siemens, Forchheim, Germany) with retrospective gating was
      used to assess the pulmonary veins. Lesion severity was determined on a semi
      quantitative scale (< 30 %, 30 - 50 %, > 50 %). RESULTS: CT was performed without
      any complications in all patients. Diagnostic image quality could be obtained in
      all examinations. The pulmonary veins showed lesions < 30 % in four patients,
      lesions of 30 -, 50 % in five patients and a stenosis > 50 % in one patient.
      Eighteen patients showed no lesions. CONCLUSION: Multidetector CT of the
      pulmonary veins seems to be able to visualize high-grade and low-grade lesions,
      but larger catheter-controlled studies are needed for further assessment of the
      diagnostic accuracy and clinical reliability of this noninvasive method.

PMID- 12525988
TI  - [Sonographical breast biopsy: how many core biopsy specimens are needed?].
AB  - PURPOSE: To determine the optimum number of specimens of a sonographically guided
      core biopsy of the breast. MATERIALS AND METHODS: From January 2001 to April
      2001, sonographically guided core biopsies (coaxial needle: 11 G; core needle: 12
      G) were performed on 106 patients with 115 BI-RADS trade mark 4-5 lesions that
      had corresponding sonographic findings. Five specimens were obtained in
      anteroposterior direction parallel to the chest wall and each specimen examined
      histologically. RESULTS: A total of 575 core biopsies produced 545 specimens
      (94.8 %), with no material obtained in 30 biopsies (5.2 %). The first and second
      specimen confirmed the diagnosis in 99 of 115 lesions (86 %), with subsequent
      specimens confirming the diagnosis in 87 % (3 rd specimen), 88 % (4 th specimen)
      and 82 % (5 th specimen). The additive accuracy of the five core breast specimens
      was 86 %, 96 %, 98 %, 99 % and 100 %. The possible volume of 78.9 mm 3 as
      determined by the sample notch of the core needle only furnished an average
      volume of 38.1 mm 3 (41.1 mm 3 for the 1 st, 40.1 mm 3 for the 2 nd, 37.5 mm 3
      for the 3 rd, 36.7 mm 3 for the 4 th and 35.0 mm 3 for 5 th core specimen).
      CONCLUSION: Sonographically guided core breast biopsy (coaxial needle: 11 G; core
      needle: 12 G) may require five passes to achieve a diagnostic accuracy of more
      than 99 %.

PMID- 12525989
TI  - [Stereotactic vacuum-assisted breast biopsy--success, histologic accuracy,
      patient acceptance and optimizing the BI-RADSTM-correlated indication].
AB  - PURPOSE: To evaluate success, histologic accuracy, patient acceptance and BI-RADS
      TM-correlated malignancy rate of stereotactic vacuum-assisted breast biopsies in
      order to optimize the indication. MATERIALS AND METHODS: In 132 patients with
      mammographically detected breast lesions 166 stereotactic vacuum- assisted 11
      gauge core biopsies were performed. All lesions were classified according to the
      BI-RADS TM categories of the ACR. Removal of the lesion was radiographically
      assessed as complete, representative or not representative. Patient acceptance
      was evaluated. RESULTS: Of the 166 lesions, 54 (32.5 %) lesions were judged
      completely removed, 110 (66.3 %) representatively removed and 2 (1.2 %) not
      representatively removed. Malignancy was found in 38 (22.9 %) lesions. The rate
      of malignancy increased from 6.3 % (2/32) for BI-RADS TM category 3 to 16.7 %
      (19/114) for BI-RADS TM category 4 and increased further to 85 % (17/20) for BI
      RADS TM category 5 (p < 0.001). The histology of a sufficient vacuum-assisted
      biopsy was underestimated in 6 (15 %) of the 40 lesions that were subsequently
      excised surgically. Most patients (98.5 %; 130/132) stated they would undergo a
      vacuum-assisted biopsy again. CONCLUSION: Vacuum-assisted breast biopsy is
      accurate, has a justifiable rate of histologic underestimation and is well
      accepted by patients. Patients with BI-RADS TM category 4 microcalcification
      benefit the most. Lesions of BI-RADS TM category 3 and BI-RADS TM category 5
      should be biopsied only under special circumstances (family risk of breast
      cancer; assessment of lesions extension).

PMID- 12525990
TI  - [Multislice CT (MSCT) in the detection and classification of pelvic and
      acetabular fractures].
AB  - PURPOSE: To assess the usefulness of MSCT in the detection and classification of
      pelvic and acetabular fractures. MATERIALS AND METHODS: Routine radiographs and
      MSCT of the pelvis with sagittal and coronal multiplanar reconstruction (MPR)
      were performed in 50 patients with clinically suspected pelvic or acetabular
      fractures. One trauma surgeon and a radiologist evaluated routine radiographs and
      CT images in terms of fracture detection, classification and visualization. The
      AO classification of fractures was used. RESULTS: MSCT excluded a suspected
      fracture in 15 patients. In the remaining 35 patients, 19 anterior pelvic ring
      fractures, 10 anterior and posterior pelvic ring fractures, 8 acetabular
      fractures and 4 sacral fractures were diagnosed. All MSCT diagnoses were made
      from the axial source images. In 7 (17 %) patients, MSCT detected additional
      fractures (2 acetabular and 5 posterior pelvic ring fractures) not seen on
      conventional radiographs. In 3 other patients, MSCT changed the fracture
      classification by delineating the full extent of the fracture. MPR visualized 7
      acetabular and 4 sacral fractures better than the axial source images.
      CONCLUSIONS: MSCT of the pelvis is needed for correct fracture detection and
      classification and has therapeutic consequences.

PMID- 12525991
TI  - [Dose reduction of radiographs of the pediatric pelvis for diagnosing hip
      dysplasia using a digital flat-panel detector system].
AB  - PURPOSE: To evaluate a possible dose reduction in pediatric pelvic radiographs in
      congenital hip dysplasia using a digital flat-panel system instead of a phosphor
      storage system. MATERIALS AND METHODS: During a six-month period, all pediatric
      patients referred for pelvic radiography for the evaluation of congenital hip
      dysplasia were randomly assigned to be examined by either a phosphor-storage
      system or a digital flat-panel system, whereby the latter system was operated
      with half the radiation dose. Thirty pairs of radiographs were assessed for the
      visibility of 16 anatomic details and for 5 orthopedic-radiographic measurements
      (5-point scale with 1 = excellent; three independent observers). The projection
      indices of Ball and Kommenda and of Tonnis and Brunken were calculated for all
      radiographs. The Student's t-test was used to compare the flat-panel and the
      phosphor-storage radiographs for observers' assessments, patients' age and
      projection indices. RESULTS: In a total of 7560 observations, the scores for the
      visibility of anatomic details and orthopedic-radiographic measurements were
      respectively 2.72 and 2.64 for the flat-panel system and 2.93 and 2.79 for the
      phosphor-storage system. No significant differences were found between both
      systems (p > 0.05) and between patient age and projection indices (p > 0.05).
      CONCLUSION: Pediatric pelvic radiographs can be obtained with a digital flat
      panel system using half the radiation dose instead of a phosphor-storage system
      without sacrificing relevant information in the diagnosis of congenital hip
      dysplasia.

PMID- 12525992
TI  - [Minimally invasive therapy of osteoid osteoma].

PMID- 12525993
TI  - [Gastrointestinal angioedema as differential diagnosis of acute abdomen].

PMID- 12525995
TI  - Molecular and cellular basis of pulmonary vascular remodeling in pulmonary
      hypertension.
AB  - Clinical pulmonary hypertension is characterized by a sustained elevation in
      pulmonary arterial pressure. Pulmonary vascular remodeling involves structural
      changes in the normal architecture of the walls of pulmonary arteries. The
      process of vascular remodeling can occur as a primary response to injury, or
      stimulus such as hypoxia, within the resistance vessels of the lung.
      Alternatively, the changes seen in more proximal vessels may arise secondary to a
      sustained increase in intravascular pressure. To withstand the chronic increase
      in intraluminal pressure, the vessel wall becomes thickened and stronger. This
      "armouring" of the vessel wall with extra-smooth muscle and extracellular matrix
      leads to a decrease in lumen diameter and reduced capacity for vasodilatation.
      This maladaptive response results in increased pulmonary vascular resistance and
      consequently, sustained pulmonary hypertension. The process of pulmonary vascular
      remodeling involves all layers of the vessel wall and is complicated by the
      finding that cellular heterogeneity exists within the traditional compartments of
      the vascular wall: intima, media, and adventitia. In addition, the developmental
      stage of the organism greatly modifies the response of the pulmonary circulation
      to injury. This review focuses on the latest advances in our knowledge of these
      processes as they relate to specific forms of pulmonary hypertension and
      particularly in the light of recent genetic studies that have identified specific
      pathways involved in the pathogenesis of severe pulmonary hypertension.

PMID- 12525996
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) should be differentiated
      from other etiologies of pulmonary hypertension since surgical intervention may
      be potentially curative. The presentation of this illness is nonspecific and may
      mimic other cardiopulmonary disease states. Without treatment, progressive
      pulmonary hypertension, right heart failure, and death will ensue.
      Echocardiography, lung ventilation-perfusion scan, right heart catheterization,
      and angiography are required for proper diagnosis and preoperative assessment.
      Definitive treatment requires surgical resection of thromboembolic material. The
      role of medical therapy remains to be defined.

PMID- 12525994
TI  - Hierarchical modeling of linkage disequilibrium: genetic structure and spatial
      relations.
AB  - Linkage disequilibrium (LD) mapping offers much promise for the positional
      cloning of disease-causing genes. However, conventional estimates of LD may
      fluctuate substantially across contiguous genomic regions, because of population
      specific phenomena such as mutation, genetic drift, population structure, and
      variations in allele frequencies. This fluctuation makes it difficult to
      interpret patterns of LD and distinguish where a causal gene is located. To
      address this issue, we propose hierarchical modeling of LD (HLD) for fine-scale
      mapping. This approach incorporates information on haplotype block structure and
      chromosomal spatial relations to refine the pattern of LD, increasing the ability
      to localize disease genes. Here, we present a framework for HLD, a simulation
      study assessing the performance of HLD under various scenarios, and an
      application of HLD to existing data. This work demonstrates that hierarchical
      modeling of linkage disequilibrium is a valuable and flexible approach for fine
      scale mapping.

PMID- 12525997
TI  - Emerging medical therapies for pulmonary arterial hypertension.
AB  - Until a few years ago, "conventional" treatment for pulmonary arterial
      hypertension (PAH) included oral anticoagulants, calcium channel blockers,
      diuretics, digoxin, and oxygen. In the 1990s, 3 randomized studies demonstrated
      that the continuous intravenous infusion of epoprostenol improved functional
      capacity, cardiopulmonary hemodynamics, and survival in patients with severe PAH.
      Recently, the thromboxane inhibitor terbogrel, the prostacyclin analogues
      treprostinil, beraprost, and iloprost, and the endothelin receptor antagonist
      bosentan have been tested in clinical trials in more than 1,100 patients. Except
      for terbogrel, all compounds have improved by different degrees the mean exercise
      capacity as assessed by 6 minutes walking distance. Conversely, these trials
      differ for the severity and etiology of included PAH patients as well as for the
      effects on combined clinical events, on quality of life, and on hemodynamics. No
      trials have shown effects on mortality, and each new compound presents different
      side effects that seem unpredictable in the individual patient. At present,
      additional new compounds such as sitaxentan, ambisentan, L-arginine, and
      sildenafil are studied in clinical trials. The new therapeutic options are
      currently in different phases of approval by regulatory agencies, and when they
      will become available we will have the opportunity to select the most appropriate
      treatment for the single patient, according to an individualized benefit-to-risk
      ratio.

PMID- 12525998
TI  - Pulmonary hypertension associated with connective tissue disease.
AB  - Pulmonary arterial hypertension is a life threatening complication of several
      connective tissue diseases including scleroderma (both diffuse and limited
      scleroderma, or the CREST syndrome--calcinosis cutis, Raynaud's phenomenon,
      esophageal dysfunction, sclerodactyly, and telangectasia), systemic lupus
      erythomatosis (SLE), mixed connective tissue disease (MCTD), and less commonly,
      rheumatoid arthritis (RA) and dermatomyositis/polymyositis. This report reviews
      the occurrence of this complication, potential etiologies, clinical presentation,
      and treatment options.

PMID- 12525999
TI  - Structure and function of the sinus node, AV node and His bundle of the human
      heart: part I-structure.

PMID- 12526001
TI  - Origin of the conformation dependence of protein charge-state distributions in
      electrospray ionization mass spectrometry.
AB  - The influence of tertiary structure on the electrospray ionization mass spectra
      of proteins is a well known and broadly exploited phenomenon. However, the
      underlying mechanism is not well understood. This paper discusses the bases and
      the implications of the two current hypotheses (solvent accessibility and
      Coulombic repulsions), pointing out the remaining open questions. Evidence
      reported here supports a third hypothesis, i.e. that intramolecular interactions
      in folded proteins play a key role in determining the observed charge-state
      distributions. It is proposed that native protein structures stabilize to a large
      extent pre-existing charges of the opposite polarity to the net charge of the
      ion, preventing their neutralization during the electrospray process. Thus, the
      higher charge states of unfolded conformations, relative to the folded structure,
      would not derive from a more extensive ionization of the former, but rather from
      a higher content of neutralizing charges in the latter. This interpretation
      allows several other problematic observations to be explained, including the
      different shapes of the spectra of folded and unfolded proteins, the
      discrepancies between observed and predicted gas-phase reactivity of protein ions
      and the apparent inconsistency of positive- and negative-ion mode results.

PMID- 12526002
TI  - Feasibility of a liquid-phase microextraction sample clean-up and liquid
      chromatographic/mass spectrometric screening method for selected anabolic steroid
      glucuronides in biological samples.
AB  - Anabolic androgenic steroids (AAS) are metabolized extensively in the human body,
      resulting mainly in the formation of glucuronide conjugates. Current detection
      methods for AAS are based on gas chromatographic/mass spectrometric (GC/MS)
      analysis of the hydrolyzed steroid aglycones. These analyses require laborious
      sample preparation steps and are therefore time consuming. Our interest was to
      develop a rapid and straightforward method for intact steroid glucuronides in
      biological samples, using liquid-phase microextraction (LPME) sample clean-up and
      concentration method combined with liquid chromatographic/tandem mass
      spectrometric (LC/MS/MS) analysis. The applicability of LPME was optimized for 13
      steroid glucuronides, and compared with conventional liquid-liquid extraction
      (LLE) and solid-phase extraction (SPE) procedures. An LC/MS/MS method was
      developed for the quantitative detection of AAS glucuronides, using a deuterium
      labeled steroid glucuronide as the internal standard. LPME, owing to its high
      specificity, was shown to be better suited than conventional LLE and SPE for the
      clean-up of urinary AAS glucuronides. The LPME/LC/MS/MS method was fast and
      reliable, offering acceptable reproducibility and linearity with detection limits
      in the range 2-20 ng ml(-1) for most of the selected AAS glucuronides. The method
      was successfully applied to in vitro metabolic studies, and also tested with an
      authentic forensic urine sample. For a urine matrix the method still has some
      unsolved problems with specificity, which should be overcome before the method
      can be reliably used for doping analysis, but still offering additional and
      complementary data for current GC/MS analyses.

PMID- 12526004
TI  - Liquid chromatographic/electrospray ionization tandem mass spectrometric study of
      the phenolic composition of cocoa (Theobroma cacao).
AB  - Liquid chromatography coupled with ionspray mass spectrometry in the tandem mode
      (LC/MS/MS) with negative ion detection was used for the identification of a
      variety of phenolic compounds in a cocoa sample. Gradient elution with water and
      acetonitrile, both containing 0.1% HCOOH, was used. Standard solutions of 31
      phenolic compounds, including benzoic and cinnamic acids and flavonoid compounds,
      were studied in the negative ion mode using MS/MS product ion scans. At low
      collisional activation, the deprotonated molecule [M - H](-) was observed for all
      the compounds studied. For cinnamic and benzoic acids, losses of CO(2) or
      formation of [M - CH(3)](-*) in the case of methoxylated compounds were observed.
      However, for flavonol and flavone glycosides, the spectra present both the
      deprotonated molecule [M - H](-) of the glycoside and the ion corresponding to
      the deprotonated aglycone [A - H](-). The latter ion is formed by loss of the
      rhamnose, glucose, galactose or arabinose residue from the glycosides. Different
      fragmentation patterns were observed in MS/MS experiments for flavone-C
      glycosides which showed fragmentation in the sugar part. Fragmentation of
      aglycones provided characteristic ions for each family of flavonoids. The optimum
      LC/MS/MS conditions were applied to the characterization of a cocoa sample that
      had been subjected to an extraction/clean-up procedure which involved
      chromatography on Sephadex LH20 and thin-layer chromatographic monitoring. In
      addition to compounds described in the literature, such as epicatechin and
      catechin, quercetin, isoquercitrin (quercetin-3-O-glucoside) and quercetin-3-O
      arabinose, other compounds were identified for the first time in cocoa samples,
      such as hyperoside (quercetin-3-O-galactoside), naringenin, luteolin, apigenin
      and some O-glucosides and C-glucosides of these compounds.

PMID- 12526003
TI  - Determination of pharmaceuticals in aqueous samples using positive and negative
      voltage switching microbore liquid chromatography/electrospray ionization tandem
      mass spectrometry.
AB  - Analytical methods were developed for atorvastatin, novobiocin and roxithromycin
      using microbore liquid chromatography/electrospray ionization tandem mass
      spectrometry (microbore LC/ESI-MS/MS) in positive and negative voltage switching
      mode. Atorvastatin and roxithromycin require the positive-ion mode, whereas the
      negative-ion mode is required for the determination of novobiocin. Using the
      positive and negative voltage switching function, the three analytes were
      determined with one injection, and the time required was half that required using
      separately run positive- and negative-ion modes, without any reduction in
      sensitivity. A microbore LC column (100 x 1.0 mm i.d.) was chosen for
      chromatographic separation with mobile phase solvents acetonitrile and 10 mM
      aqueous ammonium acetate. The flow-rate was 0.1 ml min(-1) and the injection
      volume was 1 micro l. The analytes were quantified in the multiple reaction
      monitoring mode with external standards. By switching the positive and negative
      voltage, the three analytes were determined with a 4 min chromatographic run and
      with instrumental detection limits of 1-3 pg. This analytical method, using a
      microbore LC column combined with solid-phase extraction, was applied
      successfully to the determination of trace levels of the above pharmaceuticals in
      aqueous samples. Atorvastatin was detected in a sewage treatment plant final
      effluent.

PMID- 12526005
TI  - Study of the collision-induced radical cleavage of flavonoid glycosides using
      negative electrospray ionization tandem quadrupole mass spectrometry.
AB  - Negative electrospray ionization tandem quadrupole mass spectrometry was used to
      study the collision-induced dissociation (CID) of the O-glycosidic bond from
      different commercially available flavonoid glycosides. Depending on the
      structure, flavonoid glycosides can undergo both a collision-induced homolytic
      and heterolytic cleavage of the O-glycosidic bond producing deprotonated radical
      aglycone ((Y(0) - H)(-*)) and aglycone (Y(0) (-)) product ions. The relative
      abundance of the radical aglycone to the aglycone fragment from flavonol-3-O
      glycosides increased with increasing number of hydroxyl substituents in the B
      ring and in the order kaempferol - <quercetin - <myricetin-3-O-glycoside. The
      nature and position of the sugar substitution of the flavonol glycosides also
      affected the fragmentation to the radical aglycone. Obtained under similar
      conditions, the product ion spectrum of kaempferol-7-O-neohesperidoside showed
      only a minor radical aglycone product ion as opposed to kaempferol-3-O
      rutinoside. The relative abundance of the radical aglycone to the aglycone
      fragment from flavone-7-O-glycosides was also dependent on the substitution in
      the B ring. CID of apigenin-7-O-glucoside produced relatively more of the radical
      aglycone fragment than luteolin-7-O-glucoside, while only the aglycone fragment
      was found from diosmetin-7-O-rutinoside. The position of the sugar substitution
      also affected the fragmentation of the flavone glycosides, such that the product
      ion spectrum of luteolin-4'-O-glucoside showed only the aglycone fragment as
      opposed to luteolin-7-O-glucoside. No radical aglycone fragments were found from
      the flavanone-7-O-glycosides and dihydrochalcone glycoside investigated in the
      study.

PMID- 12526006
TI  - Secondary ion and laser ablation mass spectrometry for the quantitative
      characterization of styrene-butadiene copolymers.
AB  - Styrene-butadiene copolymers were analyzed by static secondary ion mass
      spectrometry (S-SIMS) and laser ablation Fourier transform ion cyclotron
      resonance mass spectrometry (LA-FTICRMS) to obtain quantitative information based
      on specific ions. Silver deposition was performed on polystyrene, butadiene
      rubber and styrene-butadiene rubber. Under these experimental conditions, new
      secondary ions were detected, in particular silver-cationized butadiene
      [M(butadiene) - Ag](+) and styrene [M(styrene) - Ag](+) monomers. In contrast, LA
      FTICRMS experiments did not require pretreatment. At high laser power density, UV
      photons (193, 266 and 355 nm) allowed the detection of styrene and butadiene
      monomers at m/z 104 and 54, respectively. The use of the observed ions by SIMS or
      LA-FTICRMS ensures that quantitative information on the relative distribution of
      each monomer is obtained. However, the silver coating thickness in the SIMS
      experiment seems to have an important influence on the quantitative information
      obtained. For LA-FTICRMS experiments, the best results are obtained at a
      wavelength of 355 nm.

PMID- 12526007
TI  - Electron ionization-induced fragmentation of N-(alkoxymethyl)anilides.
AB  - Electron ionization-induced fragmentation patterns of the series of N
      (alkoxymethyl)acetanilides and related formanilides and benzanilides have been
      studied. The main fragmentation reaction observed for all compounds studied is
      the loss of an alkyl radical from the N-alkoxymethyl group leading to the
      appropriate protonated N-acylformanilide derivatives. This reaction is
      accompanied by unusually high kinetic energy release. Other important
      fragmentations common for majority of the compounds studied are (i) loss of an
      aldehyde molecule derived from an alkoxyl group yielding an appropriate N-acyl-N
      methylaniline, (ii) elimination of a C(n)H(2n)O(2) fragment derived from N
      alkoxymethyl group and carbonyl group oxygen atom and (iii) formation of N
      methyleneaniline radical cation.

PMID- 12526008
TI  - Structural characterization of carcinogen-modified oligodeoxynucleotide adducts
      using matrix-assisted laser desorption/ionization mass spectrometry.
AB  - The aim of this study was to determine the chemical structure of in vitro 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-modified oligodeoxynucleotides
      (ODNs) by exonuclease digestion and matrix-assisted laser desorption/ionization
      mass spectrometry. A single-stranded 11-mer ODN, 5'-d(CCATCGCTACC), was reacted
      with N-acetoxy-PhIP, resulting in the formation of one major and eight minor PhIP
      ODN adducts. A 10 min treatment of the major and one minor PhIP-ODN adduct with a
      3'-exonuclease, bovine intestinal mucosa phosphodiesterase (BIMP), and a 5'
      exonuclease, bovine spleen phosphodiesterase, results in inhibition of the
      primary exonuclease activity at deoxyguanosine (dG) producing 5'-d(CCATCG(PhIP))
      and 5'-d(G(PhIP)CTACC) product ions, respectively. Post-source decay (PSD) of
      these enzymatic end products identifies dG as the sole modification site in two
      11-mer ODN-PhIP adducts. PSD of the minor PhIP-ODN adduct digestion end product,
      5'-d(CCATCG(PhIP)), also reveals that the PhIP adducted guanine moiety is in an
      oxidized form. Prolonged treatment of the PhIP-ODN adducts at 37 degrees C with
      BIMP induces a non-specific, or endonuclease, enzymatic activity culminating in
      the formation of deoxyguanosine 5'-monophosphate-PhIP (5'-dGMP-PhIP). The PSD
      fragmentation pattern of the 5'-dGMP-PhIP [M + H](+) ion of the major adduct
      confirms PhIP binds to the C-8 position of dG. For the minor adduct, PSD results
      suggest that PhIP binds to the C-8 position of an oxidized guanine, supporting
      the hypothesis that this adduct arises from oxidative degradation, resulting in a
      spirobisguanidino structure.

PMID- 12526009
TI  - Identification of formylglycine in sulfatases by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - C(alpha)-Formylglycine, the catalytic amino acid residue in the active site of
      sulfatases, is generated by post-translational modification of a cysteine or
      serine residue. We describe a highly sensitive procedure for the detection of
      C(alpha)-formylglycine-containing peptides in tryptic digests of sulfatase
      proteins. The protocol is based on the formation of hydrazone derivatives of
      C(alpha)-formylglycine-containing peptides when using dinitrophenylhydrazine as a
      matrix for matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS). The hydrazone derivatives desorb and ionize with high
      efficiency and can be detected in the sub-femtomole range. The presence of
      C(alpha)-formylglycine is indicated by a mass increment of 180.13 u,
      corresponding to the hydrazone moiety, and also by a unique C-terminal fragment
      ion, characteristic of sulfatases, that becomes prominent in MALDI post-source
      decay mass spectra of the hydrazone derivatives.

PMID- 12526010
TI  - Clustering of nucleosides in the presence of alkali metals: Biologically relevant
      quartets of guanosine, deoxyguanosine and uridine observed by ESI-MS/MS.
AB  - Electrospray ionization (ESI) mass spectra of nucleosides, recorded in the
      presence of alkali metals, display alkali metal ion-bound quartets and other
      clusters that may have implications for understanding non-covalent interactions
      in DNA and RNA. The tetramers of guanosine and deoxyguanosine and also their
      metaclusters (clusters of clusters), cationized by alkali metals, were observed
      as unusually abundant magic number clusters. The observation of these species in
      the gas phase parallels previous condensed-phase studies, which show that guanine
      derivatives can form quartets and metaclusters of quartets in solution in the
      presence of metal cations. This parallel behavior and also internal evidence
      suggest that bonding in the guanosine tetramers involves the bases rather than
      the sugar units. The nucleobases thymine and uracil are known to form magic
      number pentameric adducts with K+, Cs+ and NH4+ in the gas phase. In sharp
      contrast, we now show that the nucleosides uridine and deoxythymidine do not form
      the pentameric clusters characteristic of the corresponding bases. More subtle
      effects of the sugars are evident in the fact that adenosine and cytidine form
      numerous higher order clusters with alkali metals, whereas deoxyadenosine and
      deoxycytidine show no clustering. It is suggested that hydrogen bonding between
      the bases in the tetramers of dG and rG are the dominant interactions in the
      clusters, hence changing the ribose group to deoxyribose (and vice versa)
      generally has little effect. However, the additional hydroxyl group of RNA
      nucleosides enhances the non-selective formation of higher-order aggregates for
      adenosine and cytidine and results in the lack of highly stable magic number
      clusters. Some clusters are the result of aggregation in the course of ionization
      (ESI) whereas others appear to be intrinsic to the solution being examined.

PMID- 12526011
TI  - Liquid chromatographic/tandem mass spectrometric method for the determination of
      the tobacco-specific nitrosamine metabolite NNAL in smokers' urine.
AB  - A specific and rapid liquid chromatographic/tandem mass spectrometric (LC/MS/MS)
      method was developed and validated for NNAL, a metabolite of the tobacco-specific
      nitrosamine metabolite NNK. The metabolite was detected in smokers' urine with a
      limit of quantitation (LOQ) of 20 pg ml(-1) and a linear range up to 1000 pg ml(
      1). The method features a single solid-phase extraction step and MS/MS monitoring
      following electrospray ionization. Fragmentation pathways for the protonated
      molecular ion are proposed. The sample preparation is simpler than that for gas
      chromatographic methods reported in the literature and maintains sensitivity
      adequate for determining NNAL in smokers' urine. By using enzyme hydrolysis to
      determine total NNAL in urine, the amount of NNAL-glucuronide was calculated. A
      standard pooled smokers' urine sample used for development gave values of 176 +/-
      8 pg ml(-1) free NNAL and 675 +/- 26 pg ml(-1) total NNAL following enzyme
      hydrolysis. The method was applied to a group of seven smokers; the free NNAL
      level for the group was 101-256 pg ml(-1) with NNAL-glucuronides at 247-566 pg
      ml(-1). The ratio of conjugated to free NNAL was in the range 0.98-2.95. The
      variability in total daily amount of NNAL excreted (ng per 24 h) had RSDs of 6
      21% for free NNAL, 7-22% for conjugated NNAL and 6-20% for total NNAL excreted.
      When normalized to the number of cigarettes smoked, the amounts of NNAL excreted
      per cigarette smoked were in the range of amounts of NNK yields reported for
      cigarettes in the literature.

PMID- 12526012
TI  - Effect of instrument tuning on the detectabilityof biopolymers in electrospray
      ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry of multiply charged biopolymer ions of
      different molecular size revealed a strong influence of tuning parameters on
      their detectability in quadrupole ion trap and triple quadrupole mass
      spectrometers. Hence, after optimizing the ion optical parameters with the signal
      of the 4- charge state of (dT)(24) (low charge state tuning), a tenfold increase
      in the signal-to-noise ratio for a mixture of oligodeoxythymidylic acids (n = 12
      18) was obtained compared with the results achieved with tune parameters
      optimized with a synthetic 80-mer oligodeoxynucleotide. By contrast, a detection
      limit in the upper femtomole region could only be reached for a 104-mer
      oligodeoxynucleotide utilizing the 24- charge state of the 80-mer (high charge
      state tuning). The same effect was observed for proteins investigated in the
      positive ion mode using low and high charge states of cytochrome c and carbonic
      anhydrase, respectively, for instrument tuning. By comparing the settings for low
      and high charge state tuning, it became obvious that the most significant
      difference was observed in the potential applied to the heated metal capillary
      used to transfer ions from the atmospheric pressure to the vacuum region of the
      ion source. Taking advantage of the optimized tuning procedure, the molecular
      mass of a 61 base pair product of polymerase chain reaction was accurately
      determined by electrospray ionization mass spectrometry on-line interfaced to ion
      pair reversed-phase high-performance liquid chromatography.

PMID- 12526013
TI  - In-gel digestion with endoproteinase LysC.

PMID- 12526015
TI  - Selective use of transthyretin and retinol-binding protein as markers in the
      postoperative assessment of protein nutritional status.
AB  - We evaluated several markers to judge the postoperative state of protein
      nutriture in eight patients following surgery for cancer. Seven patients had a
      good prognosis and had no evidence of infections or other complications.
      Following surgery, all of the patients showed a shift toward abnormal values for
      the serum concentrations of albumin, transthyretin (TT), retinol-binding protein
      (RBP), and the amino acid (AA) ratio of nonessential to essential amino acids. In
      patients without complications, the AA ratio returned to normal first. When blood
      specimens were collected at 7-day intervals, concentrations of RBP and TT were
      revealed to be decreased and recovered at the same time, or TT was recovered
      after RBP was normalized. RBP and TT were usually abnormal until the AA ratio
      became normal. Although albumin moved toward normal concentrations after RBP and
      TT, the albumin concentrations in some patients were slightly above the lower
      reference value, whereas RBP and TT were significantly below their lower
      reference limits. In these patients, assessments over the next 7-14 days showed
      persistently low values for albumin, TT, and RBP. We recommend the selective use
      of TT and RBP for the postoperative assessment of protein nutriture in surgical
      patients.

PMID- 12526016
TI  - Indices of obesity, dyslipidemia, and insulin resistance in apparently healthy
      Caribbean subjects.
AB  - Reports from developing countries indicate that a rise in the socioeconomic level
      is a risk factor for metabolic disorders. We aimed to assess the indices of
      obesity, dyslipidemia, and insulin resistance among fairly literate healthy
      adults in a multidisciplinary institution in Trinidad. The study included 156
      volunteers (46 males and 110 females, 17-40 years old). The subjects provided
      information on age, ethnicity, educational attainment, and occupation in self
      administered, closed-ended questionnaires. Waist and hip circumferences (cm),
      weight (kg), and height (m) were measured. Fasting blood samples were taken for
      glucose, insulin, and lipid determinations in 78 subjects who volunteered for
      laboratory measurements. Insulin resistance was determined with homeostasis model
      assessment (HOMA). Of the 156 subjects studied, 83% had received tertiary
      education, and had no previous record of body mass index (BMI); 8% were obese,
      17% were overweight, and 27% were underweight. Laboratory measurements in 78
      subjects revealed 28% hypercholesterolemia and 20% hyperinsulinemia. There were
      no significant gender-related differences in these prevalence rates (P>0.05). The
      identification of obesity, underweight, hyperinsulinemia, and
      hypercholesterolemia in this healthy population suggests that screening for the
      indices of metabolic disorders in a healthy population would be potentially
      useful for the early identification and treatment of metabolic-related disorders.

PMID- 12526017
TI  - Automatic analysis of normal bone marrow blood cells using the XE-2100 automated
      hematology analyzer.
AB  - The bone marrow aspiration test conventionally has been performed by visual
      methods, using a light microscope, because automatic blood cell analyzers cannot
      adequately capture erythroblasts and immature granulocytes (IGs) (Tatsumi et al.:
      Osaka City Med J 1988;34:135-146; Tatsumi et al.: Am J Clin Pathol 1986;86:50
      54). With the development of the XE-2100 automatic blood cell analyzer (Sysmex
      Corporation, Kobe, Japan) in 1999, the classification of erythroblasts and IGs by
      means of flow cytometry (Zini et al.: Infus Ther Transfus Med 2001;28:277-279;
      Briggs et al.: Sysmex J Int 1999;9:113-119) became possible. In the present study
      we classified cells in 65 bone marrow aspiration specimens by the microscopic
      method and with the XE2100, and compared the results. A good correlation was
      found in the nucleated red blood cell (NRBC), white blood cell (WBC), and total
      nucleated cell (TNC) counts; the myeloid/erythroid ratio (M/E ratio);
      neutrophils, lymphocytes, eosinophils, and IGs in the immature myeloid
      information (IMI) channel; and the total cell count. These items can all be
      analyzed in about 54 sec with the XE2100, which is faster than with the
      microscopic method. Therefore, analysis of bone marrow aspiration specimens with
      this apparatus appears to be very useful for clinical screening as well as
      laboratory testing.

PMID- 12526018
TI  - Detection of apolipoprotein E phenotype in unconcentrated cerebrospinal fluid.
AB  - We developed a simple method to detect apolipoprotein E (Apo E) polymorphism
      distribution in approximately 20 microL of unconcentrated cerebrospinal fluid
      (CSF). A combination of isoelectric focusing in 3 M urea gel and immunoblotting
      was employed. Apo E phenotypes were identified in CSF samples from 45 patients
      with probable Alzheimer disease (AD), 15 with multiple sclerosis (MS), and 25
      with other neurological diseases (OND). When the data were compared with a set of
      matched plasma samples, the results were identical. The method is useful for Apo
      E phenotyping from fresh or frozen unconcentrated CSF, when blood or plasma is
      not available.

PMID- 12526019
TI  - Effect of the traditional Chinese medicines Chan Su, Lu-Shen-Wan, Dan Shen, and
      Asian ginseng on serum digoxin measurement by Tina-quant (Roche) and Synchron LX
      system (Beckman) digoxin immunoassays.
AB  - Chan Su, Lu-Shen-Wan, Dan Shen, and Asian ginseng are traditionally used to treat
      a number of conditions, including cardiovascular disease. All of these
      traditional Chinese medicines exhibit cardioactive properties. Digoxin is a
      cardioactive drug with a narrow therapeutic range (0.8-1.9 ng/mL). A patient
      taking digoxin may also take these Chinese medicines for their cardiotonic
      effects. Moreover, the active components of these medicines that are responsible
      for cardiotonic effects bear structural similarities to digoxin. Therefore, we
      studied the potential interference of these Chinese medicines with two digoxin
      immunoassays--the Tina-quant (Roche Diagnostics) and the Beckman (Synchron LX
      system)--and compared the values with the fluorescence polarization immunoassay
      (FPIA; Abbott Laboratories). When very small amounts (2-5 microL) of aqueous
      extract of Chan Su or Lu-Shen-Wan were added to drug-free serum, we observed high
      digoxin-like immunoreactivity with the FPIA. In contrast, when ethyl acetate
      extract of Dan Shen or microliter amounts of ginseng extract were added to drug
      free serum, we observed modest digoxin-like immunoreactivity with the FPIA, but
      no apparent digoxin activity with the Roche and Beckman digoxin immunoassays.
      When aliquots of a digoxin pool prepared from patients receiving digoxin were
      supplemented with these Chinese medicines, we observed the most significant
      interference with the FPIA. The presence of endogenous digoxin-like
      immunoreactive substances can have additive effects with these Chinese medicines
      and falsely increase apparent digoxin levels by the FPIA. On the other hand, the
      Roche and Beckman assays were free from interference from DLIS but showed
      significant interference from Chan Su and Lu-Shen-Wan. We conclude that the FPIA
      showed the most significant interference from all four of the Chinese medicines
      we studied. However, the Roche and Beckman assays showed no interference from two
      (Dan Shen and Asian ginseng) of the four Chinese medicines we studied.

PMID- 12526020
TI  - Genetic analysis of chromosome 22q11.2 markers in congenital heart disease.
AB  - Congenital heart disease (CHD) is a common cardiac defect found in infants and
      children. Despite advances in diagnosis and treatment, our understanding of the
      causative mechanism and etiology of CHD is limited. To determine the genetic
      etiology of CHD, we selected 11 consecutive short tandem-repeat polymorphic
      (STRP) markers located in the interval of the 22q11.2 region to perform genotype
      analysis on a large number of CHD patients (>120) and their normal relatives
      (>220). The results show that as regards the distribution of allelic size and
      frequency of these STRP markers, there were no significant differences between
      the CHD patients and the normal volunteers. This indicates that there is no
      linkage disequilibrium with these markers in CHD. In the level of heterozygosity
      for each marker in nonsyndromic CHD and conotruncal heart defect (CTD), there
      were no significant differences between the two populations. In syndromic CHD,
      the level of heterozygosity for D22S1648 was significantly lower than that
      observed in the unaffected population (chi(2) = 11.25; P = 0.001). This suggests
      that there may be a deletion at the D22S1648 locus, and the low heterozygosity of
      D22S1648 indicates that this marker can be used as a genetic marker for detecting
      microdeletions in 22q11.2. With the use of fluorescence in situ hybridization
      (FISH) and real-time quantitative polymerase chain reaction (PCR) performed on
      syndromic patients, we confirmed the molecular results.

PMID- 12526021
TI  - Effects of peroxisome proliferator-activated receptor-gamma agonists on central
      nervous system inflammation.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a critical
      role in glucose and lipid metabolism. More recently, PPAR-gamma ligands have been
      reported to inhibit the expression of proinflammatory molecules by
      monocytes/macrophages. Of relevance to CNS disease is that PPAR-gamma agonists
      have been demonstrated to have similar effects on microglia. PPAR-gamma agonists
      also ameliorate experimental autoimmune encephalomyelitis, an animal model of
      multiple sclerosis. This Mini-Review summarizes the effects of PPAR-gamma
      agonists in mediating immune responses and the potential of these agonists in the
      treatment of inflammatory disorders of the CNS.

PMID- 12526022
TI  - Differential expression of L- and S-MAG upon cAMP stimulated differentiation in
      oligodendroglial cells.
AB  - Myelin-associated glycoprotein (MAG), an immunoglobulin-like cell signaling
      protein involved in axon-glial interactions, displays two intracellular C-termini
      as a result of alternative mRNA splicing. During brain development, the two MAG
      mRNAs that encode L-MAG and S-MAG differ in their relative abundance. We have
      investigated the differential expression of L- and S-MAG upon cAMP treatment in
      the oligodendroglial cell line Oli-neu, a cell line able to differentiate in
      vitro. We have engineered GFP and VSVG fusions by small insertions into the
      alternatively spliced exons of the cloned MAG gene and reintroduced them into Oli
      neu cells. The individually tagged MAG isoforms were expressed under the control
      of the MAG promoter and regulatory region. In this system, L-MAG was the
      predominant isoform before the stimulation of cells with cAMP, whereas upon cAMP
      treatment the S-MAG isoform was predominantly expressed in cells with a high
      degree of morphological differentiation. We suggest that the regulation of the
      MAG alternative splicing and the morphological differentiation in
      oligodendrocytes are controlled both by the same cAMP-responsive differentiation
      step.

PMID- 12526023
TI  - Gamma 1 laminin and its biologically active KDI-domain may guide axons in the
      floor plate of human embryonic spinal cord.
AB  - Immunocytochemistry, in situ hybridization and Matrigel-embedded cultures were
      used to investigate the distribution of laminins during development of the human
      embryonic spinal cord (7-11 weeks). Our results indicate that alpha 1, beta 1,
      beta 3 and gamma 1 laminins localize as punctate deposits in the floor plate
      region in association with commissural fibers crossing the ventral midline. In
      addition, the neurite outgrowth domain of gamma 1 laminin accumulates heavily in
      the floor plate region, in the notochord and in GFAP-immunoreactive glial fibers
      of the embryonic spinal cord. In culture experiments, the biologically active KDI
      domain of gamma 1 laminin selectively attracted directional outgrowth of neurites
      from explants of the dorsal spinal cord. The spatial and temporal colocalization
      of punctate deposits of laminins with nerve fibers crossing the ventral midline,
      and the guidance of neurites by the KDI-peptide domain, indicate that laminins,
      specifically the gamma 1 laminin, may be involved in guidance of axons during
      embryonic development of the human spinal cord.

PMID- 12526024
TI  - Distinct protein kinases regulate SNAP-25 expression in chromaffin cells.
AB  - The contribution of distinct Ca(2+)-sensitive protein kinases to the regulation
      of the expression of the synaptosomal-associated protein SNAP-25 was examined in
      bovine chromaffin cells. Prolonged incubation with high K(+) (38 mM) or 1,1
      dimethyl-4-phenyl-piperazinium (DMPP), a nicotinic receptor agonist,
      significantly increased SNAP-25 protein and mRNA expression, as assessed by
      immunoblotting and semi-quantitative RT-PCR analysis. Both stimuli preferentially
      enhanced mRNA coding for the SNAP-25a isoform. Increase of SNAP-25 expression
      induced by K(+) or DMPP was inhibited over 70% by KN-62 and KN-93, two
      Ca(2+)/calmodulin-dependent protein kinase (CaMK) inhibitors, whereas the
      inactive analogue KN-92 only reduced the expression by 34%. The three compounds
      also inhibited the high K(+)-elicited [Ca(2+)](i) signal by 40%, suggesting that
      the effect of KN-62 and KN-93 was a combination of CaMK/ Ca(2+) influx inhibitory
      actions. Incubation of the cells with mitogen-activated protein kinase (MAPK)
      inhibitors PD98059 and U0126 reduced protein expression elicited by high K(+) by
      50%, but did not modify the response to DMPP. Interestingly, although protein
      kinase A (PKA) inhibition by H-89 did not affect the high K(+) or DMPP-induced
      SNAP-25 expression, basal protein levels were significantly modified upon
      activation or inhibition of this pathway. Basal expression of SNAP-25 was also
      modified by the protein kinase C (PKC) activator, phorbol 12-myristate 13
      acetate, but not by Go6976, a PKC-alpha inhibitor, suggesting that the Ca(2+)
      insensitive PKC-epsilon isoform control basal expression of SNAP-25 in these
      cells. Taken together, these results provide the first evidence that diverse
      protein kinases might converge in the induction of SNAP-25 expression in
      chromaffin cells. The preferential contribution of one or another kinase would
      depend on the physiological or experimental conditions.

PMID- 12526025
TI  - Quantification of transcriptional activities of reporter gene constructs in
      primary cultures of sympathetic neurons.
AB  - Primary cultures of sympathetic neurons provide an attractive cellular model for
      investigating the mechanisms of neurotransmitter phenotypic plasticity. However,
      it has not been possible to transfect these neurons by conventional techniques,
      and this has been a major impediment to molecular investigations of neuronal gene
      expression in this system. Here, reporter plasmids were transferred into the
      nuclei of cultured sympathetic neurons by microinjection. We developed and
      improved this procedure and were able to measure the transcriptional activities
      of two coinjected promoters in small groups of neurons, and even from a single
      neuron. Promoter activities can thus be quantified and normalized relative to
      that of a constitutively expressed promoter, allowing correction for variability
      in the injection and assay procedures. High and low promoter activities can be
      reliably quantified. Importantly, this method can be used not only for reporter
      plasmids but also for DNA fragments containing only a promoter and reporter gene
      without any vector sequence that might interfere with promoter. Using this
      approach, we measured neuronal promoter activities and found that one promoter
      region of the gene encoding choline acetyltransferase was up-regulated by more
      than sevenfold by leukemia inhibitory factor. This method thus provides the means
      to investigate the function of neuronal genes and the mechanisms that regulate
      their transcription in cultured sympathetic neurons.

PMID- 12526026
TI  - Distribution of gamma-aminobutyric acid receptors in cultured adrenergic and
      noradrenergic bovine chromaffin cells.
AB  - Fluorescence imaging techniques for recording cytosolic [Ca(2+)](i) from single
      chromaffin cells were used to characterize and discriminate between cell
      subpopulations containing gamma-aminobutyric acid (GABA)(A) and GABA(B) receptor
      subtypes. By combining this methodology with the immunoidentification of
      individual chromaffin cells using specific antibodies against tyrosine
      hydroxylase (TH), phenyl-etanolamine-N-methyl transferase (PNMT), and glutamic
      acid decarboxylase (GAD) linked to different fluorescent probes, we have been
      able to ascribe single-cell calcium responses to identified adrenergic and
      noradrenergic chromaffin cells. GAD enzyme is present in 30% of the chromaffin
      cell population, located primarily in adrenergic cells; 86% of GAD(+) cells were
      also PNMT(+). GAD expression was not correlated with the presence of GABA
      receptors. GABA-responsive cells were found with equal frequency in the GAD(+)
      and GAD(-) groups. However, the expression of GABA receptors was correlated with
      the adrenergic phenotype. [Ca(2+)](i) responses to GABA were found more
      frequently in adrenergic than in noradrenergic cells. GABA(A) receptors are more
      evenly distributed; about 90% of GABA-responsive cells have them. GABA(B)
      receptors have a more restricted distribution (present in 45% of responding
      cells). The coexpression of both GABA(A) and GABA(B) subtypes is the rule; only a
      minor subpopulation (about 12%) displays exclusively GABA(B) receptors. GABA
      receptor subtypes are distributed in a similar way when chromaffin cells are
      separated according to GAD(+)/GAD(-) or PNMT(+)/PNMT(-) classifications, with
      only minor differences. These data indicate that the intrinsic GABAergic system
      in the adrenal medulla is not designed as a paracrine model in which a group of
      cells specializes in transmitter synthesis and a different group serves as a
      specific target.

PMID- 12526027
TI  - Caspase activation pathways induced by staurosporine and low potassium: role of
      caspase-2.
AB  - Apoptotic death is a physiological process with regulatory mechanisms that are
      under the control of different molecules such as caspases. These are classified
      as initiators, such as caspases-8 and -9, and effectors, such as caspases-3 and 
      7. The participation of caspase-2 in the effector phase of apoptosis has been
      commonly observed in many cell types; however, it is able to act as an initiator
      caspase, depending on the apoptotic stimulus. Cerebellar granule cells (CGCs)
      undergo apoptosis when they are transferred from high potassium (K25) to low
      potassium (K5); this process seems to be mediated by caspase-3 activation.
      Staurosporine (STS), a full strength inhibitor of kinase proteins, also induces
      apoptosis in these cells. To characterize the caspase cascade induced by two
      stimuli in the same cell type we studied the activation of different caspases in
      CGCs treated with STS or K5. We found that both K5 and STS induce the activation
      of caspase-3. This result was confirmed by the proteolytic cleavage of poly (ADP
      ribose) polymerase (PARP), an endogenous caspase-3 substrate. Caspase-2 was
      activated preferentially by STS, which showed a temporal course suggesting that
      this caspase was induced before caspase-3. The initiator caspase-9 was also
      activated by both K5 and STS, as well as cytochrome-c release. The results
      obtained in this study suggest that STS and K5 induced different activation
      caspase pathways for apoptotic cell death of CGCs.

PMID- 12526028
TI  - Loss of nicotinic receptors induced by beta-amyloid peptides in PC12 cells:
      possible mechanism involving lipid peroxidation.
AB  - The mechanisms involved in the loss of nicotinic acetylcholine receptors
      (nAChRs), seen in brains of patients with Alzheimer's disease (AD) and in
      cultured cells treated by beta-amyloid peptides (A betas), remain elusive. We
      give results to show that lipid peroxidation induced directly by A beta might be
      involved in the deficits of nAChRs. In the study, PC12 cells were treated by
      addition of 5 microM of A beta(25-35) and A beta(1-40), respectively, with or
      without a antioxidant, vitamin E. Besides significantly decreased MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide) reduction, an increased
      lipid peroxidation was detected in the cells, but no protein oxidation.
      Significant reductions in [(3)H]epibatidine and [(125)I]alpha-bungarotoxin
      binding sites and in the protein levels of the alpha 3 and alpha 7 nAChR subunits
      were observed in the cells treated with A betas. Furthermore, A beta(25-35)
      decreased the level of ubiquinone-9 in PC12 cells, but did not change the amount
      of cholesterol, providing further evidence for lipid peroxidation. Interestingly,
      when PC12 cells were pretreated by antioxidant before the addition of A betas,
      the lipid peroxidation and the decreased ubiquinone resulted from A betas were
      prohibited. The decreases of nAChR binding sites and subunit proteins resulted
      from A betas were mostly prevented by the pretreatment with antioxidant. These
      findings suggest that lipid peroxidation stimulated by A betas might be a
      mechanism for the loss of nAChRs associated with the pathogenesis of AD.

PMID- 12526029
TI  - Differential efficacy of a synthetic antagonist of VLA-4 during the course of
      chronic relapsing experimental autoimmune encephalomyelitis.
AB  - The integrin VLA-4 has been shown to play a key role in the entry of antigen
      specific T cells into the CNS during autoimmune demyelination. Treatment of
      animals with experimental autoimmune encephalomyelitis (EAE), a model of multiple
      sclerosis, with antibodies to VLA-4 is known to suppress acute disease. In the
      present study, a synthetic antagonist of VLA-4 (TBC 3486) was injected
      subcutaneously into mice adoptively sensitized for chronic relapsing EAE. TBC
      3486 was administered daily for 14 days at early (before acute signs) and late
      time points (during chronic disease). Early treatment led to marked delay in
      disease onset and reduction in clinical severity and demyelination. After
      termination of treatment, clinical severity remained lower than in controls for
      more than 1 week. TBC 3486-treated animals showing no clinical signs (at the
      height of disease in controls) displayed moderate levels of inflammation but
      little damage to myelin. Late administration of TBC 3486 to animals with chronic
      EAE had no effect clinically. Immunocytochemistry and Western blotting of CNS
      tissue from acutely treated animals supported a moderate shift toward a Th2-type
      cytokine profile after treatment. Thus, TBC 3486 effectively delayed and reduced
      the acute (but not chronic) phase of EAE, and this amelioration correlated with
      changes in the inflammatory molecule profile.

PMID- 12526030
TI  - Apolipoprotein E expression after spinal cord injury in the mouse.
AB  - Apolipoprotein E (apo-E), a protein involved in lipid metabolism and cholesterol
      transport, has been found to be up-regulated in CNS injury and is associated with
      Alzheimer's disease in humans. In this study, we show that apo-E is also up
      regulated after complete spinal cord transection in the C57BL/6 mouse. In the
      uninjured cord, the cellular localization of apo-E protein is in astrocytes, in
      individual neurons throughout the laminae except for the dorsal horn, and in
      endothelial cells of capillaries in the immediate vicinity of those neurons.
      After injury, RNA levels are elevated as early as 4 days and reach a maximal
      level between 1 and 2 weeks. Protein levels follow closely but remain up
      regulated beyond 3 weeks. Early on, the protein can be found in neutrophils and
      macrophages at the injury site and only at later times in astrocytes during the
      remodeling of white matter tracts, most prominently in degenerating parts of the
      fasciculus gracilis.

PMID- 12526031
TI  - Changes in distribution, cell associations, and protein expression levels of NG2,
      neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to
      chronic maturation of spinal cord scar tissue.
AB  - Previous studies have correlated the failure of axon regeneration after spinal
      cord injury with axons contacting scar tissue rich in chondroitin sulfate
      proteoglycans (CSPGs; Davies et al., 1999). In the present study, we have
      conducted immunohistochemical and quantitative Western blot analysis of five axon
      growth-inhibitory CSPGs and tenascin-C within stab injuries of adult rat spinal
      cord at time points ranging from 24 hr to 6 months post injury. Quantitative
      Western blot analysis showed robust increases in neurocan, tenascin-C, and NG2
      levels by 24 hr, suggesting that these molecules play a role in preventing axon
      regeneration across acutely forming scar tissue. Peak levels of 245/130 kD
      neurocan, NG2, and 250/200 kD tenascin-C were reached at 8 days, with maximum
      levels of phosphacan and 140/80 kD brevican attained later, at 1 month post
      injury. Versican V2 protein levels, however, displayed an opposite trend,
      dropping below unlesioned spinal cord values at all time points studied. Confocal
      microscopy at 8 days post injury revealed heightened immunoreactivity for
      phosphacan, NG2, and tenascin-C, particularly within fibronectin(+) scar tissue
      at lesion centers. In contrast, neurocan was displayed within lesion margins on
      the processes of stellate NG2(+) cells and, to a much lesser extent, by
      astrocytes. At 6 months post injury, 130 kD neurocan, brevican, and NG2 levels
      within chronic scar tissue remained significantly above control. Our results show
      novel expression patterns and cell associations of inhibitory CSPGs and tenascin
      C that have important implications for axon regeneration across acute and chronic
      spinal cord scar tissue.

PMID- 12526032
TI  - Glutamate and aspartate do not exhibit the same changes in their extracellular
      concentrations in the rat striatum after N-methyl-D-aspartate local
      administration.
AB  - To determine whether glutamate (Glu) and aspartate (Asp) undergo a similar
      regulation of their extracellular levels, Glu and Asp were simultaneously
      monitored in the striatum of anesthetized rats after local N-methyl-D-aspartate
      (NMDA) receptor stimulation, using 1-min in vivo microdialysis coupled to
      capillary electrophoresis with laser-induced fluorescence detection. Application
      of NMDA (10 min, 10(-3) M) through the dialysis probe induced 1) an increase
      (+50%) in Asp during the NMDA administration and 2) a surprising biphasic effect
      on Glu, with a rapid increase (+30%) and a return to baseline before the end of
      NMDA application, followed by a second increase (+40%) occurring after and linked
      to the end of NMDA administration. When studied in the presence of 10 microM
      tetrodotoxin (TTX) or 0.1 mM Ca(2+), the increase in Asp was partially TTX
      dependent, and the early increase in Glu appeared to be partially TTX and Ca(2+)
      dependent, whereas the second increase in Glu was not. The second increase in Glu
      level was still present when NMDA antagonists (AP5 or MK-801) were administered
      at the end of NMDA application. Finally, only extracellular Asp was increased
      through application of lower NMDA concentrations (10(-4) M, 10(-5) M), whereas
      extracellular Glu was not affected. In conclusion, these results suggest a
      differential control of Glu and Asp extracellular levels in rat striatum by
      distinct mechanisms linked to NMDA receptors and involving neuronal or
      nonneuronal release.

PMID- 12526033
TI  - Nitrergic dendrites in the superficial layers of the rat superior colliculus:
      retinal afferents and alternatively spliced isoforms in normal and deafferented
      animals.
AB  - The superficial layers of the rat superior colliculus (sSC) receive innervation
      from the retina and include nitrergic neurons. We have shown previously that in
      sSC, eye enucleation reduces NADPH diaphorase staining considerably in all but
      the most proximal dendrites of nitrergic neurons. We have used
      immunocytochemistry for neuronal nitric oxide synthase (nNOS) at light and
      electron microscopic levels and bilateral eye enucleation with varied survival
      times to determine the regulatory changes imposed by the direct and indirect loss
      of retinal input on apparent nNOS amount and subcellular distribution. In
      addition, we have used SDS-PAGE and immunoblotting to test alternatively spliced
      isoforms in normal and deafferented animals. Our results show that unambiguously
      identified retinal terminals contact nitrergic neurons. In normal dendrites, nNOS
      immunoreactivity was distributed almost completely within the cytoplasm of the
      dendrite and along the postsynaptic membrane at synaptic junctions, in
      association with endoplasmic reticulum, ribosomes and external mitochondrial
      membranes. In contrast, nNOS labeling was greatly reduced in sSC deprived of
      retinal projections, and could only be observed in association with mitochondrial
      membranes and postsynaptic densities. Immunoblots of the soluble fraction from
      sSC revealed a surprisingly high proportion of the beta isoform with respect to
      the alpha counterpart in normal colliculi, suggesting an increase in isoform
      proportion after enucleation, or at least maintenance of the same proportion. It
      is suggested that ultrastructural alterations observed in sSC cells of enucleated
      animals may be consequent to plastic reactions of the sSC cells in response to
      the removal of retinal afferents.

PMID- 12526035
TI  - Self-injurious behavior in rhesus monkeys: new insights into its etiology,
      physiology, and treatment.
AB  - Self-injurious behavior (SIB) is a significant human health problem frequently
      associated with profound intellectual disabilities, genetic diseases, and
      psychiatric conditions. However, it also occurs in subclinical populations and
      appears to be on the rise in adolescents and young adults. SIB is also seen in a
      small percentage of nonhuman primates that injure themselves through biting. We
      have begun to characterize SIB in rhesus monkeys to identify some of the risk
      factors associated with this disorder, and to determine the parallels with the
      human condition. In our study population, 14% of individually housed monkeys (the
      vast majority of which are males) have a veterinary record for self-inflicted
      wounding. Wounding is rare, but self-directed biting is common. SIB can be
      elicited during aggressive altercations and may be associated with husbandry
      events. Some monkeys appear to be more vulnerable to acquiring SIB. This
      increased vulnerability is associated with certain social experiences in the
      first 2 years of life and with exposure to a larger number of moderately
      stressful events as compared to controls. Monkeys with SIB also have a
      dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, indicated by a
      blunted cortisol response to mild stressors. Our findings suggest that SIB may be
      a coping strategy to reduce arousal. Biting appears to rapidly lower an
      escalating heart rate. The potentially reinforcing effects of SIB may account for
      the failure of some treatment regimens. These findings are compared to studies of
      SIB in humans, and concordances are identified.

PMID- 12526036
TI  - Degree of social contact affects the emission of food calls in the common
      marmoset (Callithrix jacchus).
AB  - The aim of this study was to investigate whether the emission of food calls in
      common marmosets (Callithrix jacchus) is influenced by different social contexts.
      Food calls are emitted by this species only in the presence of preferred food. If
      these calls have any communicative function, it may be that individuals produce
      food calls in order to call family mates toward the food source. If this is the
      case, the number of calls produced should vary in accordance with the number of
      family mates present at the moment of the discovery of the food, i.e., the fewer
      family mates nearby, the more food calls are emitted. This hypothesis was tested
      with five pairs of common marmosets, by recording the number of food calls
      emitted in four experimental conditions: 1). isolation: completely isolated from
      the family mates; 2). visual isolation: separated by a wooden panel from the
      family mates; 3). visual contact: separated by a wire-mesh from the family mates;
      and 4). physical interaction: together with the family mates. The results show
      that the proportion of intervals during which food calls were produced by the
      pairs was significantly different in the four experimental conditions. It
      decreased from the isolation and visual isolation condition, through the visual
      contact condition, reaching the lowest value in the physical interaction
      condition. The variation observed in the proportion of intervals during which
      food calls were emitted, in relation to different social contexts, is an
      indication in favor of the communicative function of this vocalization.

PMID- 12526037
TI  - Census and distribution of the golden lion tamarin (Leontopithecus rosalia).
AB  - During 1990-1992, a survey of the golden lion tamarin, Leontopithecus rosalia,
      was carried out throughout its known distribution area. Forest remnants were
      identified by visual interpretation of Landsat-TM satellite images. Localities
      occupied by L. rosalia were first identified by interviews with local people. All
      forests more than 20 ha in size, and for which two or more interviews suggested
      the presence of the species, were surveyed using "play-back" recordings of lion
      tamarin long calls. The total wild population of L. rosalia, including that of
      the Poco das Antas Biological Reserve, was estimated to be 562 individuals in 109
      groups. The lion tamarins were generally found in four major areas of forest (six
      or more groups per forest, not including Poco das Antas), with a further 12
      groups isolated in small forest patches. Currently the species' distribution is
      restricted to just four municipalities in the state of Rio de Janeiro: Silva
      Jardim, Cabo Frio, Saquarema, and Araruama. Although they are typically confined
      to lowland forest of <300 m altitude, L. rosalia was recorded at an altitude of
      550 m in one locality. Average group size varied from 3.6 to 5.7 individuals, and
      densities from 0.39 groups/km(2) to 2.35 groups/km(2) (2.17 individuals/ km(2) to
      8.53 individuals/km(2)). Six of the isolated groups found during the survey were
      successfully translocated to a forest of 2400 ha. There is now also a significant
      population of reintroduced lion tamarins. Overall, however, the possibilities for
      further expansion of the wild population are severely limited.

PMID- 12526038
TI  - Human and simian immunodeficiency virus-infected chimpanzees do not have
      increased intracellular levels of beta-chemokines in contrast to infected humans.
AB  - This study was undertaken to explain why chimpanzees infected with HIV-1 (human
      immunodeficiency virus type 1) or SIV(cpz) (simian immunodeficiency virus of
      chimpanzee) are relatively resistant to AIDS (acquired immunodeficiency
      syndrome). The numbers of beta-chemokine-positive cells were compared between
      uninfected and infected humans and chimpanzees using three-color cytofluorometry.
      In humans, the percentage of beta-chemokine-positive cells was significantly
      higher in CD8(+) T and natural killer (NK) cells than in CD4(+) T cells in both
      uninfected and HIV-1-infected individuals. In the presence of HIV-1 infection,
      however, both CD8(+) and CD4(+) T cell subsets contained significantly more beta
      chemokine-positive cells than in the absence of infection. Interestingly, in
      chimpanzees two important differences were noted. First, their percentage of beta
      chemokine-positive CD8(+) T and NK cells was significantly higher than in
      uninfected humans. Second, in contrast to humans, infection with either HIV-1 or
      with SIV(cpz) was not associated with increased numbers of beta-chemokine
      positive cells. These results indicate that: constitutive high levels of
      intracellular beta-chemokines in chimpanzees' CD8 lymphocytes and NK cells do not
      necessarily correspond to lower levels of virus replication during the chronic
      phase of infection; and increased percentages of beta-chemokine-positive cells in
      HIV-infection are not a correlate of disease resistance. The data suggest that
      neither pre-nor post-exposure levels of intracellular beta-chemokines are
      correlated with the subsequent control of disease progression.

PMID- 12526039
TI  - STAT1 and STAT3 alpha/beta splice form activation predicts host responses in
      mouse hepatitis virus type 3 infection.
AB  - Signal transducer and activator of transcription 1alpha (STAT1 alpha) is reported
      to be essential for IFN-gamma and IFN-alpha regulated gene expression, while
      STAT1 beta, an alternate splice-form, mediates only IFN-alpha-dependent gene
      expression. STAT3 alpha and STAT3 beta splice forms are also differentially
      activated in response to cytokines including IL-6 and IL-10. The aim of this
      study was to investigate whether the STAT activation will predict the host immune
      response to viral infection and possibly a therapeutic target for the treatment
      of viral infection. Mouse hepatitis virus type 3 (MHV-3) resistant strain (A/J)
      and sensitive mouse strains (BalB/cJ) were infected intraperitoneally (i.p.) with
      100 plaque form units (pfu) of MHV-3. The mice were sacrificed at the indicated
      times, and livers and spleens were immediately frozen in liquid nitrogen. Nuclear
      extracts proteins were detected by immunoblotting. STAT1 and STAT3 activation in
      spleen increased 24 to 72 hr following MHV-3 infections in both sensitive and
      resistant mouse strains. However, over this time period, the ratio of activated
      alpha to beta splice-form for STAT1 and STAT3 increased above 1.0 in resistant
      A/J mice, while the ratio fell to <0.3 in MHV-3 sensitive Balb/cJ and C3H/HeJ
      strains. Activated STAT1 alpha/beta and STAT3 alpha/beta ratio in liver were
      similar in resistant and sensitive mouse strains. Treatment of sensitive Balb/cJ
      mice with neutralizing anti-TGF-beta antibody could increase the STAT1 alpha/beta
      ratio to <1.0 in spleens, predicting enhanced rates of survival. These results
      suggested that ratio of activated STAT1 alpha/beta and STAT3 alpha/beta in mixed
      leukocytes from spleen predict the outcome to MHV-3 infection, and may be an
      important marker and therapeutic target for modification of host immune response
      to virus infection.

PMID- 12526040
TI  - Kinetics of HBV DNA and HBsAg in acute hepatitis B patients with and without
      coinfection by other hepatitis viruses.
AB  - The kinetics of hepatitis B virus (HBV) and its surface antigen (HBsAg) during
      acute hepatitis has not yet been studied accurately in a representative number of
      patients. The influence of coinfecting hepatitis viruses during the acute phase
      of infection is not known. Three to four serum samples from 21 patients with
      acute HBV monoinfection and 27 with coinfection were taken at intervals of 6-10
      days and analyzed for the number of HBV genome equivalents (ge) by real time
      polymerase chain reaction (PCR) and for HBsAg quantity using Laurell
      electrophoresis. Log HBV ge/ml decreased during the follow-up from 6.8 +/- 1.1 to
      5.1 +/- 1.0 to 4.2 +/- 0.8 to 3.3 +/- 1.1 (mean +/- SD). The half-life times of
      HBV ge increased from 1.6 days at the beginning to 4 days at the end. HBsAg
      decreased much slower: from 38 to 23 to 12 to 3.8 microg/ml. Half-life time was
      around 8 days at the beginning and 5.7 days at the end, but 11 patients showed a
      rapid elimination of HBsAg and HBV DNA. Hepatitis C virus (HCV) coinfection did
      not change the kinetics of HBV ge and HBsAg significantly. A moderate but
      significant suppression of HBV ge levels was observed in hepatitis D virus (HDV)
      coinfected patients. HBsAg levels were, however, enhanced in this cohort. In
      conclusion, the data suggest that expression and elimination of HBV is in most
      patients with acute hepatitis B not altered by coinfecting hepatitis viruses. The
      initial decrease of HBV ge and HBsAg in serum appears to be caused by decay or
      non-specific removal in the absence of replacement.

PMID- 12526041
TI  - Hepatitis B virus genotypes and serotypes in western India: lack of clinical
      significance.
AB  - To determine hepatitis B virus genotype and subtype distribution among HBV
      infected individuals with different clinical manifestations in western India,
      serum samples from 19 asymptomatic hepatitis B surface antigen carriers, 30
      chronic hepatitis B patients, 8 acute hepatitis B patients, 5 fulminant hepatitis
      B patients, and with circulating HBV DNA were genotyped and subtyped on the basis
      of the nucleotide sequence analysis of S region of the HBV genome. Genotype D was
      the predominant genotype circulating in western India (57/62; 91.93%). All 19
      asymptomatic hepatitis B surface antigen carriers, 8 acute hepatitis B patients,
      5 fulminant hepatic failure patients and 25/30 chronic hepatitis B patients were
      circulating genotype D and ayw3/ayw2 subtypes. HBV genotype A was prevalent in 8%
      (5/62) of the total number of patients and all belonged to chronic hepatitis B
      category. Subtyping analysis showed that all genotype A isolates were of subtype
      adw2. As most of the patients from different clinical categories were infected
      with HBV genotype D, it is concluded that this genotype did not influence the
      outcome of HBV infection.

PMID- 12526042
TI  - An outbreak of HBV and HCV infection in a paediatric oncology ward:
      epidemiological investigations and prevention of further spread.
AB  - Hospital-acquired hepatitis B (HBV) and C virus (HCV) infections continue to
      occur despite increased awareness of this problem among the medical community.
      One hundred six patients were infected in a haematology oncology ward for
      children, over the time period 1996 to 2000. Serum samples from 45 such patients
      and 3 from infected medical personnel were used for nucleic acid amplification.
      HBV core, as well as HCV core and hypervariable region 1 (HVR1) nucleotide
      sequences, were analysed by phylogenetic tree analysis, in order to characterise
      the epidemiological pattern of viral transmission on the ward. Samples from 32
      patients were positive for HBV-DNA or HCV-RNA by PCR. Ten patients were positive
      for both markers. Seventeen out of twenty-three HCV core gene sequences were
      found to be evolutionarily related and clustered separately from other local
      sequences in the phylogenetic tree, indicating nosocomial transmission. This was
      confirmed by analysis of HVR1 gene sequences. One nurse and one physician from
      the ward were HCV RNA positive, but their HCV sequences were not related
      evolutionarily to those of the patient cluster. Fifteen out of nineteen HBV core
      gene sequences were also clustered together and were positioned separately in the
      relevant tree. Epidemiological investigation excluded a common source infection
      and indicated that spread of infection was most likely due to inappropriate
      infection control measures on the ward. No obvious risk factors for transmission
      were identified during the retrospective survey in patients with related
      sequences, except use of multidose vials for saline and poor staff compliance
      with routine hand hygiene procedures. The preventive measures that were
      introduced reduced the incidence of infection significantly. No new cases of HBV
      infection and only three anti-HCV seroconversions occurred over a period of 19
      months. The introduction and maintenance of strict prevention measures over a 2
      year period, combined with HBV vaccination, reduced significantly the incidence
      of new HCV and HBV infections.

PMID- 12526043
TI  - Prevalence and clinical significance of circulating cryoglobulins in HIV-positive
      patients with and without co-infection with hepatitis C virus.
AB  - Although hepatitis C virus (HCV) is a recognized cause of circulating
      cryoglobulins, the role of human immunodeficiency virus (HIV) in the pathogenesis
      of cryoglobulinemia has not been investigated extensively. To evaluate the
      prevalence of circulating cryoglobulins and to assess the relationship with
      clinical and virological parameters, 162 HIV-positive subjects (84 anti-HCV(+))
      were tested for cryoglobulins, C3, C4, RF, autoantibodies, HIV-viral titer, and
      CD4(+) count. Anti-HCV-positive subjects were tested for HCV-RNA, HCV-viral
      titer, and HCV genotype. All patients were examined for the presence of signs or
      symptoms of vasculitis and tested for cryoglobulins using a standard biochemical
      assay. Cryoglobulins were found in 30 (18.5%) cases. Of the 30 positive cases, 29
      (96.7%) were anti-HCV-positive and 28 (93.3%) HCV-RNA-positive. The presence of
      cryoglobulins was significantly associated (P < 0.01) with HCV-RNA positivity (OR
      = 27), liver cirrhosis (OR = 16), decreased levels of C3 (OR = 8.6), C4 (OR =
      13.6), increased levels of IgG and IgM (OR = 6.1 and 7.9, respectively), and RF
      positivity (OR = 6.3), but was unrelated to CD4(+) cell count, HIV viral load,
      diagnosis of AIDS, HCV viral load and the presence of autoantibodies.
      Interestingly, the presence of cryoglobulins was not significantly associated
      with signs and symptoms commonly associated with cryoglobulinemia. In conclusion,
      HIV infection does not seem to play a significant role in the production of
      circulating cryoglobulins, which strongly correlates with HCV co-infection and
      liver cirrhosis. Typical signs and symptoms of cryoglobulinemia do not correlate
      with the detection of circulating cryoglobulins in HIV and HCV patients.

PMID- 12526044
TI  - Intermittent detection of hepatitis C virus (HCV) in semen from men with human
      immunodeficiency virus type 1 (HIV-1) and HCV.
AB  - HCV is usually transmitted via the blood, but HCV RNA has been detected recently
      in seminal fluid. This study was done to study HCV seminal shedding and factors
      that could influence the presence of HCV in the seminal fluid of men coinfected
      with HCV and HIV-1. HCV and HIV-1 genomes were assayed in multiple paired blood
      and semen samples obtained from 35 men enrolled in an assisted medical
      procreation protocol. HCV RNA was found intermittently in semen samples from 9
      patients (25.7%). Samples from 9 men with HCV RNA in their semen and 26 men
      without were compared to further analyze these parameters. No correlation was
      found between HCV RNA in the seminal fluid and age, HCV virus load, the duration
      of HIV-1 infection, HIV treatment, the CD4(+) cell count, HIV-1 virus load or HIV
      1 detection in the semen. The intermittent detection of HCV RNA in semen samples
      support the systematic search for HCV RNA in semen and the use of processed
      spermatozoa in assisted medical procreation of infertile HCV serodiscordant
      couples.

PMID- 12526045
TI  - Changes in hypervariable region 1 of the envelope 2 glycoprotein of hepatitis C
      virus in children and adults with humoral immune defects.
AB  - The N-terminal end of the hepatitis C virus (HCV) envelope glycoprotein E2
      contains a stretch of 27 amino acids that exhibit increased variability. This
      hypervariable region 1 (HVR-1), as it is normally referred to, is thought to
      contain epitopes that come under humoral immune attack. In the present study, 10
      patients (5 children and 5 adults) with humoral immune defects and chronic HCV
      infection were investigated, to see how HVR-1 sequences behave over time in these
      patients who are unable to produce antibodies. Amplicons of this region showed
      little or no variation at all over time, indicating that quasispecies variation
      in this region is driven by the host's humoral immune response.

PMID- 12526046
TI  - Processing of hepatitis C virus core protein is regulated by its C-terminal
      sequence.
AB  - Polyprotein processing of plus-strand RNA viruses is important in the regulation
      of gene production and replication. The core protein of hepatitis C virus (HCV),
      constructing the viral particle, is processed from its precursor polyprotein and
      observed as two forms, p23 and p21. Production of p21 by cleavage at the C
      terminus of p23 is considered crucial to viral assembly and replication. In this
      study, this processing step was compared between clones isolated from two
      patients with fulminant hepatitis and from five patients with chronic hepatitis
      by an in vitro translation assay and cell transfection assay. The p21 core
      protein was predominant from the clone isolated from one of the fulminant
      hepatitis patient (p21 core protein production was 65.98%), while p23 was
      abundant with clones from five chronic hepatitis patients (p21 core protein
      production was 7.11+/-1.62%) and clone from another fulminant hepatitis patient
      (p21 core protein production was 13.36%). Investigations with chimeric and
      mutation-introduced constructs revealed that four amino acid residues in the C
      terminus of the core region are responsible for this difference. The data suggest
      that core protein processing is regulated by C-terminus mutations.

PMID- 12526047
TI  - Hepatitis C virus molecular epidemiology in Uzbekistan.
AB  - The aim of this study was to identify hepatitis C virus (HCV) genotypes and to
      estimate their prevalence in various risk groups and the regional distribution in
      Uzbekistan. Preliminary serological screening of 1,269 subjects revealed 6.5%
      anti-HCV-positive in a general population, 27.1% in patient groups, and 51.7%
      among intravenous drug users. HCV genotypes of 104 anti-HCV-positive subjects
      were determined using a PCR-genotyping system in core region, and the results
      were supported by nucleotide sequencing of the NS5B region. Genotype 1b
      identified in total 64.2%, was the most prevalent. The genotype 3a identified in
      25.0% was the second one distributed. HCV genotypes 2a, 1a, 2b, and 3b were
      identified in 3.8%, 2.9%, 2.9%, and 1.0% of cases, respectively. The intravenous
      drug users were distinguished from other groups by having the highest prevalence
      of genotype 3a, i.e., 50.0%, higher than the 33.3% for genotype 1b in this group.
      Geographically, genotype 1b was common; genotype 3a was also found frequently in
      all three regions. Uncommon HCV genotypes (1a, 2a, 2b, and 3b) were found in
      comparatively greater variability in the western region. Molecular evolutionary
      analysis based on the NS5B region did not reveal specific clustering or
      indigenous strains among Uzbekistan HCV isolates. In summary, two main mechanisms
      of HCV infection distribution were observed in Uzbekistan: HCV 1b genotype
      infection is widespread through blood products, and HCV 3a genotype infection is
      spreading through the growing number of intravenous drug users.

PMID- 12526048
TI  - Association of amino acid substitution pattern in nonstructural protein 5A of
      hepatitis C virus genotype2a low viral load and response to interferon
      monotherapy.
AB  - Patients with low titer (<0.5 mEq/ml) of hepatitis C virus (HCV) genotype 2a
      achieve high and sustained response (SR) rates to interferon (IFN) monotherapy,
      but we also encounter patients who are resistant to therapy. We explored the
      relationship between response to IFN and virological differences in such
      patients. We evaluated 159 consecutive naive patients with low titer of HCV
      genotype 2a who received IFN monotherapy. A case-control study matched for age,
      sex, and viral load was conducted to examine the substitution patterns in amino
      acid positions (amino acids) 2163-2254 of nonstructural (NS) 5A between
      nonresponders to ideal IFN dose (>/=500 million units) (nonresponders; NR) and
      responder to less than ideal dose. Overall, 82.4% achieved SR. The substitution
      numbers in amino acids 2193-2254 were higher in SR than NR patients (P < 0.05).
      High proportions of patients with substitution at amino acid 2205 (mainly
      threonine [T] instead of alanine [A]), dual amino acids 2169 and 2205 (mainly A-T
      instead of T-A), and those without substitution at amino acids 2227 were NR (P <
      0.05). Four of 7 NR patients achieved SR after receiving a second course of IFN.
      Their amino acids patterns at positions probably associated with sensitivity to
      IFN did not change at the start of initial and second therapies except for one
      patient, and they had lower viral load and were treated with higher IFN dose in
      the second course compared with the initial course. Our results suggest that
      substitution patterns in NS5A in patients with low titer of HCV genotype 2a may
      affect their response to IFN, but the response to therapy may be affected by
      mechanisms other than substitutions in this region.

PMID- 12526049
TI  - Hepatitis C virus infection among pregnant women in Yaounde, Cameroon:
      prevalence, viremia, and genotypes.
AB  - Central Africa is considered to be an area of high endemic hepatitis C infection.
      To determine the prevalence of anti-HCV antibodies, HCV RNA, and the genotype
      distribution in Cameroon, 1,494 pregnant women attending antenatal care units in
      Yaounde, Cameroon were screened for HCV infection. Anti-HCV antibodies were
      detected with a 3rd generation ELISA (Monolisa anti-HCV plus version 2, BioRad,
      Richmond, CA). All anti-HCV antibody-positive sera were then tested with another
      3rd generation ELISA (AxSYM) HCV version 3, Abbott Laboratories, Abbott Park, IL)
      and subsequently for HCV RNA (Amplicor HCV, Roche Diagnostics, Basel,
      Switzerland). Genotype was determined by phylogenetic analysis of the NS5b gene.
      Seventy-three pregnant women were found to be anti-HCV antibody positive by the
      first ELISA, but only 28 were anti-HCV positive by both ELISA. The prevalence of
      anti-HCV antibodies was thus 1.9% (28/1,494) (95% CI: 1.3-2.7%). 21/28 (75%) of
      the positive samples by both ELISA were HCV RNA positive. The 45 samples that
      were HCV antibody negative by the second ELISA were also HCV RNA negative. The
      HCV subtypes identified were 1a (24%), 2f (38%) and 4f (38%). In contrast to
      previous studies, anti-HCV antibodies were rare among pregnant women in Cameroon.
      The percentage of HCV seropositive pregnant women who had circulating HCV RNA was
      similar to that observed in Europe. Several HCV genotypes were found in Cameroon.

PMID- 12526050
TI  - Swine HEV infection in south India and phylogenetic analysis (1985-1999).
AB  - Hepatitis E is endemic in India. It was recently noted that although all the
      Indian human hepatitis E virus (HEV) isolates (1976-2001) were placed in genotype
      I, the swine HEV recovered from western India (2000) belonged to genotype IV.
      This was in contrast to reports from the United States and Taiwan wherein both
      human and swine HEV belonged to the same genotype, i.e., genotypes III and IV,
      respectively. In order to validate these findings further, we retrospectively
      examined serum samples collected from pigs from southern India. Sequential serum
      samples from 45 (1985-1987) and 12 (1999) pigs from Karnataka state, south India,
      were screened for the presence of HEV RNA (nested PCR) and IgG-anti-HEV (ELISA).
      PCR products (Open Reading Frame-2 region) were sequenced and subjected to
      phylogenetic analysis. In this study, 42/45 (1985-1987) and 12/12 (1999) pigs
      showed seroconversion to IgG anti-HEV antibodies, with a mean age at
      seroconversion of 4.8 +/- 1.6 months. Four samples collected in 1999 and two
      samples collected during 1985 were HEV RNA positive. All swine HEV sequences
      clustered with genotype IV, demonstrating that swine HEV was prevalent among
      south Indian pigs for at least for 16 years and, similar to western India,
      belonged to genotype IV. Thus, genotype I and IV HEV continue to circulate in
      humans and pigs, respectively, from India. Whether swine HEV infects humans
      remains to be determined.

PMID- 12526051
TI  - Polymerase chain reaction as a rapid diagnostic tool for therapy of acute retinal
      necrosis syndrome.
AB  - Herpesviruses are involved in the pathogenesis of acute retinal necrosis syndrome
      (ARN). A rapid and accurate diagnosis of herpetic infections is crucial for
      prompt administration of a specific antiviral therapy. The purpose of this study
      was to evaluate a polymerase chain reaction (PCR)-based assay to detect
      herpesvirus DNA in the aqueous humor of clinical samples from ten patients with
      uveitis and clinical suspicion of ARN. Samples were assayed for herpes simplex
      virus type 1-2 (HSV 1-2), varicella zoster virus (VZV) and cytomegalovirus (CMV).
      Clinical suspicion of ARN was confirmed for four patients. Two patients (one with
      bilateral ARN) tested PCR-positive for VZV DNA and the other two were positive
      for HSV 1-2 DNA. CMV DNA was not detected in any of the samples, and no sample
      was positive for DNA from more than one virus. The remaining patients did not
      show any evidence of herpesvirus DNA in their aqueous samples. Our findings
      demonstrate that the use of PCR for detecting herpesvirus DNA in aqueous humor of
      uveitic subjects may be a valuable tool for early diagnosis of acute retinal
      necrosis syndrome and for timely administration of a suitable therapy.

PMID- 12526052
TI  - Quantitation of cytomegalovirus (CMV) DNA by real-time PCR for occurrence of CMV
      disease in HIV-infected patients receiving highly active antiretroviral therapy.
AB  - In HIV-infected patients treated with highly active antiretroviral therapy
      (HAART) included in the Predivir cohort, we have evaluated the usefulness of CMV
      DNA quantitation by a TaqMan PCR assay from peripheral blood leukocytes (PBLs) to
      predict CMV disease occurrence. In parallel with the immune restoration after
      treatment by HAART, the percentage of positive samples decreased progressively
      from 7.3% at Day 0 to 3.5% at Month 12. Among the CMV markers, the smallest
      concordance with PBL CMV TaqMan PCR, as evaluated by kappa, was observed with
      pp65 antigenemia, whereas concordance with all other CMV markers was high. Among
      the 16 patients with CMV DNA copies at least once >100/150,000 cells, CMV disease
      occurred in six during follow-up, whereas among the 159 patients with CMV DNA
      copies always <10/150,000 cells, CMV disease occurred in three and among the
      seven patients with CMV DNA copies >10 and <100 occurred in only one. In
      univariate Cox models, all the CMV markers including PBL CMV TaqMan PCR
      >10/150,000 cells (RR: 27.6, IC95: 7.1-107.2), the CD4 cell count <75 cells/mm(3)
      and the HIV viral load >100,000 copies/ml were predictive for CMV disease. In a
      stepwise multivariate analysis, which should be interpreted with caution due to
      the small number of events (n = 10), three covariates were associated
      independently with CMV disease: pp65 antigenemia >100 nuclei/200,000, PBL CMV
      TaqMan PCR >10 copies/150,000 cells and HIV viral load remaining or increasing
      >100,000 copies/ml.

PMID- 12526053
TI  - Genetic characterization of new Dobrava hantavirus isolate from Greece.
AB  - The first complete genome sequence of Dobrava hantavirus isolated from yellow
      necked mouse Apodemus flavicollis trapped in the northeastern Greece is
      described. The S, M, and L segments of the Greek isolate of Dobrava virus are
      1673, 3635, and 6532 nucleotides (nt) long, respectively, and encode the
      nucleocapsid (N) protein of 429 amino acids (aa), glycoprotein precursor of 1135
      aa, and the L protein of 2151 aa. N protein contains three cysteine residues
      conserved in all known hantaviruses, as well as structural domains responsible
      for the RNA binding and presumable interaction with the apoptosis enhancer Daxx.
      All cysteine residues and glycosylation sites that are conserved among G1G2
      sequences of all hantaviruses species were also found in the Greek isolate. The L
      protein contains all the polymerase motifs and structural domains found in other
      hantavirus polymerases. Comparison of the Greek isolate of Dobrava virus with
      other hantaviruses showed the highest level of sequence homology with Dobrava
      virus isolate from Slovenia. Other hantaviruses carried by Murinae rodents
      (Saaremaa, Hantaan, Seoul, and Thailand viruses) were more divergent and
      hantaviruses carried by Arvicolinae or Sigmodontinae rodents showed the highest
      genetic diversity with the Greek isolate of Dobrava. The results of phylogenetic
      analyses confirmed these observations and showed a monophily of all the Dobrava
      virus strains that, in turn, shared more ancient ancestors first with Saaremaa
      virus and then with other Murinae-borne hantaviruses.

PMID- 12526054
TI  - EBNA-1 sequence variations reflect active EBV replication and disease status or
      quiescent latency in lymphocytes.
AB  - EBV infects most of the global population, but only a small percentage of
      infected individuals develop EBV-associated malignancies. Host and viral factors
      may play a role in determining the clinical outcome. Because EBNA-1 functions as
      an oriP binding protein and links the episomal viral DNA to metaphase
      chromosomes, variation of EBNA-1 has been suggested to contribute to determining
      the tissue tropism of EBV and the development of various EBV-associated diseases.
      Five subtypes have been described, according to the amino acid at residue 487: P
      ala (B95-8 prototype), P-thr (aa 487 ala to thr), V-val, V-pro and V-leu. Other
      studies, however, concluded that EBNA-1 sequence variation simply reflects the
      geographical distribution of EBV. To clarify these possibilities, we collected
      DNA samples from healthy individuals and patients with various EBV-associated
      diseases in Taiwan for PCR amplification and DNA sequencing. The results indicate
      that: 1) V-val EBNA-1 was detected in patients with nasopharyngeal carcinoma
      (NPC) and other EBV-associated malignant diseases; 2) the prototype P-ala strain
      was detected only in peripheral blood lymphocytes; 3) mixed populations of
      different subtypes of N-terminal and C-terminal sequences were observed in
      samples from one patient with nasopharyngeal carcinoma, one with T lymphoma and
      one with infectious mononucleosis sample; 4) intermediate variations between P
      ala and V-val were observed in T-lymphoma, Hodgkin disease and infectious
      mononucleosis samples; and 5) in comparison with the major sequences identified
      in healthy carriers, the EBNA-1 sequences in peripheral lymphocytes from
      nasopharyngeal carcinoma were mixed types in 4 of 5 patients, implying increasing
      frequency of V-val might correlate with the progression of nasopharyngeal
      carcinoma.

PMID- 12526055
TI  - Enterovirus infection may induce humoral immune response reacting with islet cell
      autoantigens in humans.
AB  - Molecular mimicry is one of the mechanisms by which enterovirus infections have
      been postulated to have a role in the pathogenesis of type 1 diabetes.
      Immunogenic epitopes in enterovirus capsid protein VP1 and procapsid protein VP0
      have sequence similarities with diabetes-associated epitopes in tyrosine
      phosphatase IA-2/IAR and heat shock protein 60. In the present study, documented
      enterovirus infection was shown to induce humoral responses, that in 7% and 1% of
      patients cross-reacted with the known diabetes-associated epitopes in tyrosine
      phosphatase IAR and heat shock protein 60, respectively. In contrast, none of the
      children vaccinated against poliomyelitis had antibodies to the diabetes
      associated epitope of tyrosine phosphatases IA-2/IAR. The antibody response
      studied in serum samples from six patients with coxsackievirus A9 infection was
      mainly targeted to capsid protein VP1. Coxsackievirus A9 infection induced
      antibodies cross-reacted with one epitope in heat shock protein 60, but not with
      epitopes derived from other autoantigens. Most diabetic children had high levels
      of antibodies to both coxsackievirus and poliovirus derived VP1 peptides but the
      pattern of reactivity did not differ from that seen in healthy children. The
      reactivity of linear epitopes derived from autoantigens was low in general and
      associated with the presence of multiple autoantibodies in the patients. Some
      linear auto-epitopes derived from tyrosine phosphatase IA-2, glutamic acid
      decarboxylase 65, preproinsulin, and heat shock protein 60 were recognized by
      sera from diabetic patients, but not by sera from healthy children. In
      conclusion, enteroviruses may induce immune responses that react with islet cell
      autoantigens, which is a concern when a putative inactivated enterovirus vaccine
      is considered.

PMID- 12526056
TI  - IgG antibodies to human papillomavirus 16, 52, 58, and 6 L1 capsids: case-control
      study of cervical intraepithelial neoplasia in Japan.
AB  - In Japan, human papillomavirus (HPV) 16, 52, and 58 are most commonly associated
      with cervical intraepithelial neoplasia (CIN). By contrast, HPV6 is primarily
      associated with genital warts. This study was designed to evaluate the
      association between IgG antibody responses to common HPVs and the risk of CIN
      development within a Japanese population. CIN cases (n = 141) and controls (n =
      109) were tested for cervical HPV DNA and serum IgG antibodies to L1 capsids of
      HPV16, 52, 58, and 6. Seropositivity to HPV16, 52, and 58 L1 capsids was
      significantly higher in CIN cases than in controls: 27%, 21%, and 31% versus 16%,
      11%, and 11%, respectively (P < 0.05). HPV6 L1 seropositivity was not
      significantly associated with CIN lesions (P = 0.11). Presence of viral DNA for
      either HPV16, 52, or 58 correlated with a significant antibody response against
      the homologous L1 capsids but not heterologous L1 capsids. Furthermore,
      seropositivity to multiple types of HPV16, 52, and 58 was more strongly
      associated with an increased risk of CIN development than seropositivity to a
      single type (P for trend <0.001). These findings indicate that IgG antibodies to
      L1 capsids of HPV16, 52, and 58 represent an increased risk of CIN development,
      with antibodies to multiple types being indicative of a further increase in risk.
      The presence of CIN lesions in women with seropositivity to multiple types
      suggests that viral exposure to a given type may not be protective against
      infections by other types and subsequent CIN development.

PMID- 12526057
TI  - IgG subclasses in human immune response to wild and attenuated (vaccine) Junin
      virus infection.
AB  - Different proportions of IgG subclasses have previously been reported to
      distinguish the immune response elicited by primary and recurrent viral
      infections, as well as viral vaccines. The goal of this study was to study the
      IgG subclasses composition in the immune response of patients with Argentine
      hemorrhagic fever, and vaccinees with Candid #1 strain of Junin virus. Twenty
      four individuals inoculated with Candid #1 vaccine and 67 patients with Argentine
      hemorrhagic fever were studied. Blood samples were drawn at 30, 60, and/or 180
      days post-inoculation with Candid #1 and 30, 60, and 90 days after clinical onset
      of the disease. Specific anti-Junin virus IgG subclasses were titrated with
      specific human monoclonal antibody fluorescence isothiocyanate conjugate (FITC)
      by immunofluorescent assay (IFA). IgG(1) anti-Junin virus was found in every
      subject studied and IgG(3) was also detected in some patients with a severe form
      of Argentine hemorrhagic fever. IgG(2) and IgG(4) were not detected in any serum
      sample studied. The mean titer of specific IgG(1) in vaccinees was significantly
      lower than in patients with Argentine hemorrhagic fever (P < 0.05), but no
      difference was found between mild and severe cases of the disease (P > 0.05). The
      results of this study demonstrated a central role of IgG(1) in human recovery
      from infection with every strain of Junin virus, an observation stressed by the
      immune response to Candid #1 vaccine, which resulted in no difference in IgG
      subclasses composition from that found in mild cases of Argentine hemorrhagic
      fever.

PMID- 12526058
TI  - Induction of cellular immunity to varicella-zoster virus glycoproteins tested
      with pernasal coadministration of Escherichia coli enterotoxin in mice.
AB  - A mutant of Escherichia coli enterotoxin promotes the induction of cellular
      immunity to a live varicella vaccine (the Oka strain) as a mucosal adjuvant in
      mice. An investigation was carried out to determine which of the purified
      glycoproteins of the virus among three induced cellular immunity with a single
      nasal administration. Spleen cells from mice immunized nasally with the vaccine
      and toxin produced interleukin-2 (IL-2) at the same level on restimulation in
      vitro with glycoprotein H: glycoprotein L (gH:gL), gB, and gE:gI, but not IL-4.
      The spleen cells from mice immunized with gH:gL, gB, or gE:gI and toxin produced
      IL-2 on restimulation with gH:gL, gB, or gE:gI, respectively, and the vaccine,
      but not IL-4. Immunization with gH:gL and the toxin showed increased thymidine
      uptake and production of IL-2 and interferon-gamma (IFN-gamma) of the spleen
      cells, but not IL-4, depending on the dose of gH:gL used for immunization and
      restimulation in vitro. Purified gE:gI and gB have been reported to be the
      strongest stimulators of cellular immunity to varicella upon subcutaneous
      injection and are useful as a subunit vaccine. All the glycoproteins tested are
      excellent stimulators of cellular immunity to the virus and itself on nasal co
      immunization with the toxin.

PMID- 12526060
TI  - Election 2002 update: the fallout for NIH appropriations.

PMID- 12526062
TI  - Integration of advanced technologies to enhance problem-based learning over
      distance: Project TOUCH.
AB  - Distance education delivery has increased dramatically in recent years as a
      result of the rapid advancement of communication technology. The National
      Computational Science Alliance's Access Grid represents a significant advancement
      in communication technology with potential for distance medical education. The
      purpose of this study is to provide an overview of the TOUCH project (Telehealth
      Outreach for Unified Community Health; http://hsc.unm.edu/touch) with special
      emphasis on the process of problem-based learning case development for
      distribution over the Access Grid. The objective of the TOUCH project is to use
      emerging Internet-based technology to overcome geographic barriers for delivery
      of tutorial sessions to medical students pursuing rotations at remote sites. The
      TOUCH project also is aimed at developing a patient simulation engine and an
      immersive virtual reality environment to achieve a realistic health care scenario
      enhancing the learning experience. A traumatic head injury case is developed and
      distributed over the Access Grid as a demonstration of the TOUCH system. Project
      TOUCH serves as an example of a computer-based learning system for developing and
      implementing problem-based learning cases within the medical curriculum, but this
      system should be easily applied to other educational environments and disciplines
      involving functional and clinical anatomy. Future phases will explore PC versions
      of the TOUCH cases for increased distribution.

PMID- 12526063
TI  - Virtual patient simulator for distributed collaborative medical education.
AB  - Project TOUCH (Telehealth Outreach for Unified Community Health;
      http://hsc.unm.edu/touch) investigates the feasibility of using advanced
      technologies to enhance education in an innovative problem-based learning format
      currently being used in medical school curricula, applying specific clinical case
      models, and deploying to remote sites/workstations. The University of New
      Mexico's School of Medicine and the John A. Burns School of Medicine at the
      University of Hawai'i face similar health care challenges in providing and
      delivering services and training to remote and rural areas. Recognizing that
      health care needs are local and require local solutions, both states are
      committed to improving health care delivery to their unique populations by
      sharing information and experiences through emerging telehealth technologies by
      using high-performance computing and communications resources. The purpose of
      this study is to describe the deployment of a problem-based learning case
      distributed over the National Computational Science Alliance's Access Grid.
      Emphasis is placed on the underlying technical components of the TOUCH project,
      including the virtual reality development tool Flatland, the artificial
      intelligence-based simulation engine, the Access Grid, high-performance computing
      platforms, and the software that connects them all. In addition, educational and
      technical challenges for Project TOUCH are identified.

PMID- 12526064
TI  - Anatomy and the access grid: exploiting plastinated brain sections for use in
      distributed medical education.
AB  - Computerized animation is becoming an increasingly popular method to provide
      dynamic presentation of anatomical concepts. However, most animations use
      artistic renderings as the base illustrations that are subsequently altered to
      depict movement. In most cases, the artistic rendering is a schematic that lacks
      realism. Plastinated sections provide a useful alternative to artistic renderings
      to serve as a base image for animation. The purpose of this study is to describe
      a method for developing animations by using plastinated sections. This
      application is used in Project TOUCH as a supplemental learning tool for a
      problem-based learning case distributed over the National Computational Science
      Alliance's Access Grid. The case involves traumatic head injury that results in
      an epidural hematoma with transtentorial uncal herniation. In addition, a
      subdural hematoma is animated permitting the student to contrast the two
      processes for a better understanding of dural hematomas, in general. The method
      outlined uses P40 plastinated coronal brain sections that are digitized and to
      which contiguous anatomical structures are rendered. The base illustration is
      rendered, interpolated, and viewed while audio narration describes the event.
      This method demonstrates how realistic anatomical animations can be generated
      quickly and inexpensively for medical education purposes by using plastinated
      brain sections.

PMID- 12526066
TI  - Role of viruses and atypical bacteria in exacerbations of asthma in hospitalized
      children: a prospective study in the Nord-Pas de Calais region (France).
AB  - We studied the role of viruses and atypical bacteria in children hospitalized
      with exacerbated asthma by a prospective study of children with acute asthma
      admitted to the Department of Pediatrics in Lille, and to 15 hospitals in the
      Nord-Pas de Calais region, from October 1, 1998-June 30, 1999. We included
      children aged 2-16 years with active asthma, defined as three or more recurrent
      episodes of reversible wheezing. The severity of asthma and of asthmatic
      exacerbations was recorded. Immunofluorescence assays (IFA) on nasopharyngeal
      secretions (NPS), serological tests, or both, were used for detection of
      influenza virus, respiratory syncytial virus (RSV), adenovirus, parainfluenza
      virus, and coronavirus. Polymerase chain reaction (PCR) assays on NPS were used
      for rhinovirus and enterovirus. Serological tests for Chlamydia pneumoniae and
      Mycoplasma pneumoniae were performed. A control group of asymptomatic asthmatic
      outpatients was examined for respiratory viruses (using IFA and PCR). Eighty-two
      symptomatic children (mean age, 7.9 years) were examined. Viruses were detected
      in 38% (enterovirus, 15.8%; rhinovirus, 12%; RSV, 7.3%). Serological tests for
      atypical bacteria were positive in 10% of patients (C. pneumoniae, 5%; M.
      pneumoniae, 5%). Among the 27 control subjects (mean age, 7.9 years), one PCR was
      positive for enterovirus. There was no correlation between severity of chronic
      asthma or asthmatic exacerbations and the diagnosis of infection. Atypical
      bacterial pathogen infections were linked with prolonged asthmatic symptoms. In
      conclusion, we confirmed the high incidence of viral infection in acute
      exacerbations of asthma, especially enteroviruses or rhinoviruses. Persistent
      clinical features were more frequently associated with atypical bacterial
      infections, suggesting that these infections should be investigated and treated
      in cases of persistent asthmatic symptoms.

PMID- 12526067
TI  - Effects of bracing on lung function in idiopathic juvenile kyphosis.
AB  - Although considerable information is available on the effects of bracing on lung
      function in kyphoscoliosis, there is a paucity of data on idiopathic juvenile
      kyphosis (IJK). The present study was designed to investigate the immediate
      effect of bracing on lung function in children and adolescents with mild-to
      moderate IJK. Spirometry, measurement of lung volumes, and arterial oxyhemoglobin
      saturation (SaO(2)) were performed in 24 patients, 9-17 years of age, who were
      treated with a corrective brace for mild-to-moderate IJK (Cobb angle, 46-75
      degrees ). Children were studied when braced and unbraced. When children were
      unbraced, mean percent predicted values (+/-standard deviation) for total lung
      capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and
      forced expiratory volume in 1 sec (FEV(1)) were 100.0% (+/-13.0%), 92.7% (+/
      14.2%), 108.2% (+/-20.4%), and 95.0% (+/-16.3%), respectively. With the brace on,
      significant reductions occurred in all lung function measurements: TLC decreased
      by 9.5% (P < 0.001), VC by 9.3% (P = 0.001), FRC by 14.2% (P = 0.005), and FEV(1)
      by 8.9% (P = 0.009). SaO(2) decreased from 96.2% (+/-1.6%) to 95.2% (+/-1.4%) (P
      = 0.027). An inverse relationship was observed between pre- and postbracing
      change in TLC and Cobb angle children (P = 0.021). Our findings indicate that
      corrective bracing in mild-to-moderate IJK results in mild lung restriction and a
      clinically insignificant drop in SaO(2). The effect of bracing on TLC decreases
      as the severity of kyphosis increases in these patients.

PMID- 12526068
TI  - Surgical treatment of pulmonary hydatid cysts in pediatric patients.
AB  - Hydatid cyst is a zoonotic infection that is caused by Echinococcus granulosus
      and alveolaris, and that can result in endemics in rural regions. Infections
      caused by Echinococcus granulosus are more commonly seen in our country. In this
      retrospective study, we aimed at discussing the experience we have accumulated on
      pediatric pulmonary hydatid cyst cases over the last 6 years. Between 1995-2001,
      in the Department of Thoracic and Cardiovascular Surgery in Gaziantep University,
      38 cases underwent 39 operations due to pulmonary and hepatic hydatid cysts. Of
      these, 24 were males and 14 were females, with an age range of 2-16 years.
      Operations were frequently performed via thoracotomy. Nineteen cysts were intact,
      and 26 were perforated. One case had sternotomy, another had sequential
      thoracotomy, and the rest of the cases underwent thoracotomy, which resulted in
      cystotomy-capitonnage. In the postoperative period, 2 patients had sustained air
      leakage, and 2 other cases developed skin infections. Average hospital stay was 5
      days. After the operation, the patients received chemotherapy (albendazole 10
      mg/kg/day) for 1.5 months. Early or late deaths or recurrences were not observed.
      We conclude that cystotomy-capitonnage is a successful treatment for pediatric
      pulmonary hydatid cysts, as it preserves the parenchyma. Chemotherapy in the
      postoperative period is beneficial in preventing the recurrences.

PMID- 12526069
TI  - Comparative randomized trial of azithromycin versus erythromycin and amoxicillin
      for treatment of community-acquired pneumonia in children.
AB  - Our objective was to compare the clinical efficacy of azithromycin vs.
      erythromycin and amoxicillin in the treatment of presumed bacterial community
      acquired pneumonia in ambulatory children, and to evaluate the etiologies of
      these illnesses. One hundred and ten children, aged 1 month to 14 years, were
      enrolled between January 1996-January 1999. Children were distributed into two
      groups according to clinical and radiological patterns: classic or atypical
      pneumonia. Patients with classic pneumonia were randomly assigned to receive oral
      amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days;
      patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days,
      or erythromycin 50 mg/kg/day for 14 days. Chest X-ray, clinical, and laboratory
      parameters were obtained on enrollment. Clinic visits were performed on days 3,
      7, and 14, and chest X-ray follow-up on days 7 and 14. Microbiological diagnosis
      of classic pathogens was based on blood and bronchial secretion cultures. The
      diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae
      was based on PCR and serologic tests.Forty-seven children met the criteria for
      classic pneumonia (23 children received azithromycin, and 24 received
      amoxicillin), and 59 children had atypical pneumonia (33 children were treated
      with azithromycin, and 26 with erythromycin). Demographic characteristics at
      enrollment were similar between children with classic pneumonia treated with
      azithromycin and erythromycin and children treated with azithromycin and
      erythromycin for atypical pneumonia. However, on day 7, children with classic
      pneumonia who received azithromycin normalized their chest X-ray more often than
      those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The
      same was true for children with atypical pneumonia; their chest X-rays had
      normalized by day 14 (100% in those with azithromycin vs. 81% in those with
      erythromycin, P = 0.059). Also, children with atypical pneumonia treated with
      azithromycin had earlier cessation of cough than children treated with
      erythromycin (3.6 +/- 1.9 vs. 5.5 +/- 3.6 days respectively, P = 0.02). There
      were only three children with side effects (mild diarrhea, all in the
      erythromycin group). Etiological agents were identified in 41% of children. In
      conclusion, azithromycin is an effective therapeutic option for the treatment of
      community-acquired classic and atypical pneumonia in children.

PMID- 12526070
TI  - Antimicrobial susceptibility profile of molecular typed cystic fibrosis
      Stenotrophomonas maltophilia isolates and differences with noncystic fibrosis
      isolates.
AB  - Multiresistance in Stenotrophomonas maltophilia limits the effectiveness of
      antimicrobial therapy for infections due to this organism. It can be of special
      concern in cystic fibrosis (CF) patients due to frequent antimicrobial
      administration. The in vitro activity of 41 antimicrobial agents against 76
      epidemiologically defined CF S. maltophilia isolates by pulsed-field-gel
      electrophoresis (PFGE) technique under XbaI and SpeI restriction was compared
      with that obtained with 51 non-CF strains recovered from respiratory sources.
      Minimal inhibitory concentrations (MICs) were determined with the standard
      National Committee for Clinical Laboratory Standards agar dilution technique, but
      with 24-hr incubation. Forty-seven different PFGE profiles were observed within
      76 S. maltophilia CF isolates. Minocycline (resistance rate, 0%; MIC(90), 1
      microg/ml), doxycycline (6.4%; 8 microg/ml), trovafloxacin (4.2%; 2 microg/ml),
      moxifloxacin (6.3%; 2 microg/ml), clinafloxacin (6.3%; 2 g/ml), and moxalactam
      (17.0%; 64 g/ml) displayed low resistance rates. On the contrary, resistance
      rates were higher with ceftazidime (70.0%; 256 microg/ml), cefepime (83.0%; 128
      microg/ml), piperacillin (87.2%; >1,024 microg/ml), ticarcillin (87.2%; >512
      microg/ml), and aztreonam (95.7%; >1,024 microg/ml). Clavulanate reverted
      resistance to ticarcillin and aztreonam in 40.4% and 31.7% of strains,
      respectively. Aminoglycosides displayed reduced activities with susceptibility
      rates lower than 20% and MIC(90) higher than 128 microg/ml. With the exception of
      trimethoprim-sulfamethoxazole (25.4 vs. 31.3%), CF isolates were more resistant
      than non-CF isolates. Remarkably, resistance was enhanced in S. maltophilia
      isolates persistently recovered in chronically colonized patients. Susceptibility
      analysis demonstrated higher resistance rates among CF S. maltophilia isolates
      when compared with respiratory isolates from non-CF patients. Moreover,
      persistently recovered CF S. maltophilia isolates were more resistant than
      sporadic non-CF isolates.

PMID- 12526071
TI  - Three-minute step test to assess exercise capacity in children with cystic
      fibrosis with mild lung disease.
AB  - The information obtained from a simple submaximal test (the 3-min step test) was
      compared with that from a maximal cycle ergometry study, in a group of children
      with CF with relatively mild abnormalities of lung function (FEV(1) > 50%
      predicted). Nineteen subjects with CF undertook both exercise tests on the same
      day. Measurements included heart rate (HR), oxygen saturations (SaO(2)), visual
      analogue score of perceived breathlessness (VAS), 15-count breathlessness score
      (15c), and peak oxygen consumption (VO(2)). There were significant differences in
      the median changes in HR and VAS during the cycle test compared to the step test,
      78 vs. 46 beats per minute (P < 0.05) and 51 mm vs. 42 mm (P < 0.05),
      respectively. There were no differences between median changes in 15c and SaO(2),
      but 3 subjects had significant desaturations (>4%) during the cycle test only.
      Significant exercise desaturations may occur in mild CF lung disease and will not
      be detected by a 3-min step test. The 15c did not discriminate between a maximal
      and a submaximal test, and was less useful than VAS. Important information may be
      missed by the step test which is detected by more complex exercise tests.

PMID- 12526072
TI  - Asthma-specific quality of life questionnaires in children: are they useful and
      feasible in routine clinical practice?
AB  - This study used well-validated quality of life (QOL) instruments to compare the
      QOL scores achieved by children aged 7-17 years with the views of their parents
      of the effects of their child's asthma on family life. Also, a comparison was
      made between the child's QOL scores and the judgment of the clinician in charge
      in regard to asthma control. There was poor correlation between the overall
      scores of the children and the overall caregiver's score (r = 0.19, P = 0.18),
      and no correlation between the child's score and assessment of control given by
      the clinician in charge of the case (r = 0.02, P = 0.98). It is important to
      recognize that there may be little relationship between the concerns of the child
      regarding his or her asthma, the effects on the family as reported by a parent,
      and the clinician's view of asthma control. This recognition may significantly
      affect treatment planning with the family. The administration of the QOL
      instrument used in this study was straightforward and quite quick, with a mean
      time to completion of about 8 min.

PMID- 12526073
TI  - Long-term noninvasive mechanical ventilation for children at home: a national
      survey.
AB  - Experience with domiciliary noninvasive mechanical ventilation (NIMV) in children
      is limited. The aim of this study was to determine the number of patients and
      categorize the use of domiciliary NIMV in children in France. An anonymous cross
      sectional national study was performed, using a postal questionnaire sent to all
      specialist centers utilizing domiciliary NIMV for chronic respiratory failure.
      Patients aged <18 years and receiving home NIMV were included in the study.
      Detailed information was obtained from 102 patients from 15 centers: 4/15 centers
      cared for 84% of patients; 7% of patients were under 3 years old; 35% were
      between 4-11 years old; and 58% were older than 12 years. Underlying diagnoses
      included neuromuscular disease (34%), obstructive sleep apnea (OSA) and/or cranio
      facial abnormalities (30%), cystic fibrosis (17%), congenital hypoventilation
      (9%), scoliosis (8%), and other disorders (2%). NIMV was started because of
      nocturnal hypoventilation (67%), acute exacerbation (28%), and/or failure to
      thrive (21%). Volume-targeted ventilation was preferred in restrictive disorders
      (56%) and central hypoventilation (56%), while pressure support ventilation (PSV)
      was preferred in cystic fibrosis (71%). Patients with OSA and/or cranio-facial
      abnormalities were ventilated with continuous positive airway pressure (45%) or
      bilevel PSV (52%). In conclusion, NIMV is currently used in France for the
      domiciliary management of children with a variety of conditions causing chronic
      respiratory failure. However, NIMV in children is still performed on a small
      scale, and combined with the heterogeneity of the patient population, its
      application would best be served by centers specializing in the initiation and
      long-term follow-up of these patients.

PMID- 12526074
TI  - Maximal static respiratory pressures in children and adolescents.
AB  - This study was designed to establish reference values of maximal static
      respiratory pressures in children and adolescents in our community, and compare
      them with previous studies. Participants were recruited from three schools
      (randomly chosen from those located in the metropolitan area of the city of
      Valencia) after appropriate consent. None of the participants had a previous
      history of pulmonary, cardiac, and/or skeletal abnormalities, and all of them had
      normal spirometry. Forced spirometry (Spirotrac III, Vitalograph) and maximal
      inspiratory (P(ImaxRV)) and expiratory (P(EmaxTLC)) pressure values (Sibelmed
      163) were obtained by the same investigator, following national guidelines (SEPAR
      1990).We studied 392 subjects (185 males, 207 females) whose ages ranged from 8
      17 years. The reproducibility of measurements was investigated in a subgroup of
      88 participants (randomly selected from the total sample, and stratified for age
      and gender) by means of the intraclass correlation coefficient (P(EmaxTLC), 0.98;
      P(ImaxRV), 0.95). P(EmaxTLC) and P(ImaxRV) values were significantly different
      between males and females (P < 0.0001) and were normally distributed. A stepwise,
      linear multiple regression model was built in each gender group (male/female) for
      the prediction of P(ImaxRV) and P(EmaxTLC) values. Independent variables (weight,
      height, and age) and their potential interactions were forced to enter the model
      in order to maximize the square of the multiple correlation coefficient of the
      resultant equation. This model turned out to be applicable (homoscedasticity,
      independence, and normality requirements) for P(ImaxRV) (in males and females)
      and for P(EmaxTLC) (in males but not in females). Variables included in the model
      were age and the product of weight and height. Their predictive power ranged
      between 0.21-0.51. In conclusion, P(ImaxRV) and P(EmaxTLC) values increase with
      age from 8 until 17 years. In all age groups, values were higher in males than in
      females. Weight, height, and age are included in the predictive equations for
      P(ImaxRV) (in males and females) and P(EmaxTLC) (in males). Their predictive
      value is similar to that reported by other authors and ranges between 0.21-0.51.
      This model is not suitable for the prediction of P(EmaxTLC) in females; the
      observed mean and range should be used instead.

PMID- 12526075
TI  - Validation of shuttle tests in children with cystic fibrosis.
AB  - Shuttle tests are simple, inexpensive field tests that have been used to estimate
      the cardiorespiratory status of children. It has yet to be validated in children
      with CF. The aim of this study was to assess the reproducibility and criterion
      validity of shuttle tests in children with cystic fibrosis (CF). Ninety-three CF
      patients aged 6 to 16 years of age with a wide range of disease severity
      performed the study. The 10-m shuttle test was used for children 7 years of age
      and younger and those deemed too chronically ill by their physicians to perform
      the longer test (n = 35.) All other children performed the 20-m shuttle test (n =
      58). Reproducibility and criterion validity were assessed for each child over a
      two week period. Gas analysis was performed throughout testing using a
      polargraphic gas analyzer. The 10-m shuttle tests were reproducible (mean
      difference between tests VO(2) 2.41 mL/kg/min, CI 3.46,-0.18) and the difference
      from treadmill testing was not statistically significant (mean difference VO(2)
      5.30 mL/kg/min, CI-7.46, 1.18). The 20-m shuttle tests were reproducible (mean
      difference between tests VO(2) 2.07 mL/kg/min, CI-3.90,0.60) and the difference
      from treadmill testing was not statistically significant (mean difference VO(2)
      3.50 mL/kg/min, CI-4.90, 1.60). We conclude that when formal exercise testing
      with treadmill or cycle ergometer cannot be performed, the shuttle tests provide
      a reproducible and valid alternative.

PMID- 12526076
TI  - Treatment of cast bronchitis with low-dose oral azithromycin.
AB  - Cast or plastic bronchitis is an unusual disorder that is rarely encountered in
      the pediatric population. It is characterized by the expectoration of large,
      branching plugs of airway debris. These "casts" conform to the shape of portions
      of the tracheobronchial tree, and give the disorder its name. Cast bronchitis is
      typically seen in association with several primary pulmonary disorders and
      cyanotic congenital heart disease. It can be classified as inflammatory or
      acellular, based on the histologic characteristics of the casts. The presence of
      large, obstructive plugs filling the airways of lobes or entire lungs can result
      in a variety of clinical signs and symptoms, and may ultimately lead to
      respiratory failure and death. Conventional treatment of cast bronchitis has
      focused on the clearance of obstructing material from the airways combined with
      therapy for any underlying cardiopulmonary disease. Unfortunately, this approach
      has not proven very effective, and patient mortality remains high. We report on a
      case in which a patient with cast bronchitis was treated with long-term, low-dose
      oral azithromycin. This therapy resulted in clinical, spirometric, and
      radiographic improvement of the patient.

PMID- 12526077
TI  - Chronic Pneumocystis carinii pneumonia associated with extensive pneumatocele
      formation in a child with human immunodeficiency virus infection.
AB  - We describe a 12-year-old boy with Pneumocystis carinii pneumonia complicated by
      extensive pneumatocele formation as the presenting manifestation of human
      immunodeficiency virus infection. This report emphasizes the importance of
      considering Pneumocystis carinii infection in the differential diagnosis of
      pneumonia associated with pneumatocele formation in children.

PMID- 12526078
TI  - Acute neurological deficits in a young adult with cystic fibrosis.
AB  - An abrupt onset of a neurological deficit is a rare occurrence in patients with
      cystic fibrosis (CF). As many CF patients have indwelling intravenous catheters,
      one of the complications may be deep venous thrombosis. Cerebral thromboembolism
      through an intracardiac shunt should be considered in CF patients who develop
      unexplained acute neurological deficits. We report on the case of a 19-year-old
      CF patient with insulin-dependent diabetes mellitus who was on oral
      contraceptives and had a Port-A-Cath(R) in place. The patient developed an acute
      neurological deficit after pulmonary function testing. Radiologic investigations
      of her head and neck were unremarkable, except for bilateral maxillary and
      ethmoid sinusitis. An electroencephalogram showed epileptiform discharges
      primarily from the right hemisphere. A transthoracic echocardiogram (TTE)
      revealed a small thrombus in the right atrium. A transesophageal echocardiogram
      (TEE) demonstrated a left-to-right shunt through a patent foramen ovale (PFO)
      that was not found by TTE. Extensive investigation to rule out congenital and
      acquired thrombophilia was negative. Treatment consisted of aspirin and
      discontinuation of oral contraceptives and vitamin K supplementation. Spontaneous
      complete recovery of the neurological deficits occurred within 24 hr after onset
      of symptoms.We conclude that paradoxical embolism should be in the differential
      diagnoses of CF patients who have indwelling intravenous catheters and who
      develop an unexplained stroke. An extensive investigation to rule out
      intracardiac abnormalities and thrombophilia should be considered. The risks and
      benefits of PFO closure vs. prophylactic anticoagulant and antiplatelet
      aggregation treatment in this group of patients should be carefully weighed.

PMID- 12526079
TI  - The "wandering needle".
AB  - Suspected aspiration of a radiopaque foreign body can easily be confirmed by a
      chest film. We report a case of a boy with chest-film confirmed aspiration of a
      needle into his right main bronchus, in whom no needle was found during
      bronchoscopy. In retrospect, the boy had expectorated the needle without noticing
      it in the interval between making the diagnosis and the actual bronchoscopy. We
      propose to reconfirm aspiration of a radiopaque foreign body by fluoroscopy
      shortly before commencing bronchoscopy.

PMID- 12526080
TI  - Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and
      gelatinases in human atherosclerosis infected with Chlamydia pneumoniae: the
      potential role of Chlamydia pneumoniae infection in the progression of
      atherosclerosis.
AB  - Chlamydia pneumoniae infection implicated as an important etiologic factor of
      atherosclerosis, especially in coronary artery disease (CAD), was found in vitro
      to be associated with the induction of matrix metalloproteinases (MMPs). An
      extracellular matrix metalloproteinase inducer (EMMPRIN)/ membrane-type 1 matrix
      metalloproteinase (MT1-MMP) system which induces and activates MMPs, is suggested
      to be functional and were upregulated in the failing myocardium. However, the
      upstream regulation of MMPs by C. pneumoniae within atheroma itself remains
      unclear. We evaluated the seroepidemiologic study of C. pneumoniae infection in
      CAD patients (n= 391) and controls (n=97) and performed histopathological and in
      vitro analysis in atherosclerotic vascular tissues obtained from patients with
      seropositive to C. pneumoniae (n=20), by using immunochemistry for C. pneumoniae,
      EMMPRIN/MT1-MMP, MMP-2, and MMP-9. The seropositive rates of both anti-C.
      pneumoniae IgG and IgA were 56.7% in CAD group and 43.3% in control group
      (P=0.033). Seropositive rate was increased in subgroups of CAD patients without
      conventional coronary risk factors compared to those with conventional risk
      factors. Immunoreactivities of EMMPRIN, MT1-MMP, MMP-2, and MMP-9 were increased
      in the atheromatous plaque itself, predominantly in immunoreactive
      macrophages/mononuclear cells to C. pneumoniae. Furthermore, Western blot
      analysis showed that EMMPRIN and MMP-2 were detected more prominently in
      atherosclerotic tissues infected with C. pneumoniae compared to control tissues.
      Zymographic analysis revealed that activities of MMP-2 and MMP-9 were more
      increased in atherosclerotic tissues infected with C. pneumoniae compared to
      control tissues. The present study demonstrated upstream regulation of MMPs can
      be induced by C. pneumoniae within atheromatous plaque itself. These findings
      help to understand the potential role of C. pneumoniae in the progression of
      atherosclerosis.

PMID- 12526081
TI  - Neural cell adhesion molecule (NCAM) promotes the differentiation of hippocampal
      precursor cells to a neuronal lineage, especially to a glutamatergic neural cell
      type.
AB  - Rat hippocampal precursor cells isolated from hippocampi of embryonic day 16.5
      (E16.5) rat embryos were found to proliferate in the presence of basic fibroblast
      growth factor. Addition of soluble neural cell adhesion molecule (NCAM) to these
      precursor cells reduced cell proliferation in a dose dependent manner and
      enhanced the induction of precursor cells' differentiation to the neuronal
      lineage. Given these findings that NCAM induces the differentiation of
      hippocampal precursor cells, we investigated possible effects of NCAM on the
      expression of basic helix-loop-helix (bHLH) transcription factors during the
      differentiation. Soluble NCAM upregulated the transcription of bHLH transcription
      factors, neurogenin1 and NeuroD, but decreased HES5. Western blot analysis showed
      that NCAM increased the expression levels of CaMKII, p-MAPK, GluR1 and NR1 but
      decreased p-STAT3. These results support a role for NCAM in the inhibition of
      proliferation and the induction of neural differentiation of hippocampal neural
      precursor cells, and act as developmental regulators of the bHLH families,
      ultimately leading to the generation of glutamatergic neural cell types in the
      differentiation of hippocampal precursor cells.

PMID- 12526082
TI  - Characterization and epitope mapping of two monoclonal antibodies against human
      CD99.
AB  - CD99 plays a critical role in the diapedesis of monocytes, T cell
      differentiation, and the transport of MHC molecules. Engagement of CD99 by
      agonistic monoclonal antibodies has been reported to trigger multifactorial
      events including T cell activation as well as cell-cell adhesion during
      hematopoietic cell differentiation. In this study, to identify the functional
      domains participating in the cellular events, we mapped the epitopes of CD99,
      which are recognized by two agonistic CD99 monoclonal antibodies, DN16 and YG32.
      Using recombinant fusion proteins of GST with whole or parts of CD99, we found
      that both antibodies interact with CD99 molecules independently of sugar
      moieties. DN16 mAb detected a linear epitope located in the amino terminal region
      of CD99 while YG32 mAb bound another linear epitope in the center of the
      extracellular domain. To confirm that the identified epitopes of CD99 are
      actually recognized by the two mAbs, we showed the presence of physical
      interaction between the mAbs and the fusion proteins or synthetic peptides
      containing the corresponding epitopes using surface plasmon resonance analyses.
      The dissociation constants of DN16 and YG32 mAbs for the antigen were calculated
      as 1.27 x 10(-7) and 7.08 x 10(-9) M, respectively. These studies will help
      understand the functional domains and the subsequent signaling mechanism of CD99.

PMID- 12526083
TI  - Effects of glutamate on dehydroascorbate uptake and its enhanced vulnerability to
      the peroxidation in cerebral cortical slices.
AB  - Pro-oxidant properties of ascorbate have been studied with uses of brain tissues
      and neuronal cells. Here we address potential mechanism of ascorbate coupling
      with glutamate to generate oxidative stress, and the role which oxidized
      ascorbate (dehydroascorbate) transport plays in oxidative neuronal injury.
      Ascorbate in neurones can be depleted by adding glutamate in culture medium since
      endogenous ascorbate can be exchanged with glutamate, which enhances
      ascorbate/dehydroascorbate transport by depleting ascorbate in the neurons with
      the glutamate- heteroexchange. However, ascorbate is known readily being oxidized
      to dehydroascorbate in the medium. Glutamate enhanced the dehydroascorbate uptake
      by cells via a glucose transporter (GLUT) from extracellular region, and
      cytosolic dehydroascorbate enhanced lipid peroxide production and reduced
      glutathione (GSH) concentrations. Iso-ascorbate, the epimer of ascorbate was
      ineffective in generating the oxidative stress. These observations support the
      current concept that the high rates of dehydroascorbate transport via a GLUT
      after the release of ascorbate by glutamate leads to peroxidation, the role of
      glutamate on ascorbate/dehydroascorbate recycling being critical to induce
      neuronal death via an oxidative stress in the brain injury.

PMID- 12526084
TI  - Spatio-temporal expression patterns of Runx2 isoforms in early skeletogenesis.
AB  - Skeletogenesis occurs through either intramembranous or endochondral
      ossification. In addition, some parts of the skeletal components maintain their
      cartilaginous characteristics throughout life without mineralization. Runx2 is
      known to be a pivotal transcription factor for all skeletogenic processes. In
      this study, we examined the expression patterns of two major isoforms of Runx2 in
      early skeletogenesis. During intramembranous bone formation, Runx2-type I (Runx2
      I) was widely expressed in osteoprogenitor cells and active osteoblasts, while
      Runx2-type II (Runx2-II) expression was stringently restricted to cells lining
      mineralized bones. Cells in permanent cartilage expressed collagen type II (Col
      II) but never expressed Runx2 or Col-X. These permanent cartilages were well
      circumscribed by Runx2-I positive cells, in which Runx2-II was negative. In
      endochondral bone formation, Runx2 expression temporarily disappeared in Col-II
      positive proliferating chondrocytes, but a secondary surge of Runx2-I expression
      occurred in the prehypertrophic zone before the mineralization of cartilage.
      Collectively, both Runx2 isoforms showed very similar expression patterns in
      active bone forming areas; however, Runx2-I has an exclusive role in the early
      commitment stage of intramembranous or endochondral bone forming processes or in
      cells surrounding permanent cartilage.

PMID- 12526085
TI  - Phosphorylation of 46-kDa protein of synaptic vesicle membranes is stimulated by
      GTP and Ca2+/calmodulin.
AB  - The release of neurotransmitter is regulated in the processes of membrane docking
      and membrane fusion between synaptic vesicles and presynaptic plasma membranes.
      Synaptic vesicles contain a diverse set of proteins that participate in these
      processes. Small GTP-binding proteins exist in the synaptic vesicles and are
      suggested to play roles for the regulation of neurotransmitter release. We have
      examined a possible role of GTP-binding proteins in the regulation of protein
      phosphorylation in the synaptic vesicles. GTPgammaS stimulated the
      phosphorylation of 46 kDa protein (p46) with pI value of 5.0-5.2, but GDPbetaS
      did not. The p46 was identified as protein interacting with C-kinase 1 (PICK-1)
      by MALDI-TOF mass spectroscopy analysis, and anti-PICK-1 antibody recognized the
      p46 spot on 2-dimensional gel electrophoresis. Rab guanine nucleotide
      dissociation inhibitor (RabGDI), which dissociates Rab proteins from SVs, did not
      affect phosphorylation of p46. Ca(2+)/calmodulin (CaM), which causes the small
      GTP-binding proteins like Rab3A and RalA to dissociate from the membranes and
      stimulates CaM-dependent protein kinase(s) and phosphatase, strongly stimulate
      the phosphorylation of p46 in the presence of cyclosporin A and cyclophylin.
      However, RhoGDI, which dissociates Rho proteins from membranes, reduced the
      phosphorylation of p46 to the extent of about 50%. These results support that p46
      was PICK-1, and its phosphorylation was stimulated by GTP and Ca(2+)/CaM directly
      or indirectly through GTP-binding protein(s) and Ca(2+)/CaM effector protein(s).
      The phosphorylation of p46 (PICK-1) by GTP and Ca(2+)/CaM may be important for
      the regulation of transporters and neurosecretion.

PMID- 12526086
TI  - Phosphorylation of glycogen synthase kinase-3beta at serine-9 by phospholipase
      Cgamma1 through protein kinase C in rat 3Y1 fibroblasts.
AB  - Phospholipase Cgamma1 (PLCgamma1) plays an important role in controlling cellular
      proliferation and differentiation. PLCgamma1 is overexpressed in some tumors, and
      its overexpression induces solid tumors in nude mice. However, the regulatory
      mechanisms underlying PLCgamma1-induced cell proliferation are not fully
      understood. Here we show that overexpression of PLCgamma1 highly phosphorylated
      glycogen synthase kinase-3beta (GSK-3beta) at serine-9 in 3Y1 fibroblasts.
      Inhibition of protein kinase C (PKC)s with GF109203X abrogated GSK-3beta
      phosphorylation by PLCgamma1. We also found that steady-state level of cyclin D1
      protein, but not cyclin D1 mRNA, was highly elevated in response to serum
      stimulation in PLCgamma1-transfected cells as compared with vector-transfected
      cells. Since GSK-3beta is involved in cyclin D1 proteolysis in response to
      mitogenic stimulation, PLCgamma1-mediated GSK-3beta phosphorylation may function
      as a regulation of cyclin D1 accumulation in PLCgamma1-overexpressing cells.

PMID- 12526087
TI  - Statin inhibits interferon-gamma-induced expression of intercellular adhesion
      molecule-1 (ICAM-1) in vascular endothelial and smooth muscle cells.
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as
      statins, are widely used for primary and secondary prevention of coronary artery
      atherosclerosis. Pathogenesis of atherosclerosis is multistep processes where
      transendothelial migration of various leukocytes including monocytes is a crucial
      step. Interferon-gamma (IFN-gamma) contributes in this process by activating
      macrophages and T-lymphocytes, and by inducing adhesion molecules in vascular
      endothelial and smooth muscle cells. In this study we investigated the expression
      of intercellular cell adhesion molecule-1 (ICAM-1) in transformed endothelial
      cell line ECV304 cells as influenced by lovastatin, tumor necrosis factor-alpha
      (TNF-alpha) and IFN-gamma. Results show that lovastatin suppresses expression of
      ICAM-1 by inhibiting the IFN-gamma-induced extracellular signal-regulated kinase
      (ERK) p44/p42-STAT1 signaling pathway. In cells treated with lovastatin and IFN
      gamma, ICAM-1 was expressed at a lower level than in cells treated with IFN-gamma
      alone. However, lovastatin does not reduce TNF-alpha induced expression of ICAM
      1. A similar result was observed in cells treated with the MEKK inhibitor PD98059
      and IFN-gamma. Cis-acting DNA sequence elements were identified in the 5'
      flanking region of the ICAM-1 promoter that mediate inhibition by lovastatin;
      these sequences map to the IFN-gamma activated site which also binds the STAT1
      homodimer. However, lovastatin did not inhibit IFN-gamma-mediated induction of
      the Y701 phosphorylated form of STAT1. But lovastatin does inhibit the IFN-gamma
      mediated phosphorylation of ERK1/ERK2 (T202/Y204) and S727 phosphorylation of
      STAT1. TNF-alpha does not induce phosphorylation of ERK1/ERK2 and S727 in ECV304
      and smooth muscle cells. The results provide the evidences that statins may have
      beneficial effects by inhibiting IFN-gamma action in atherosclerotic process

PMID- 12526088
TI  - Triptolide sensitizes lung cancer cells to TNF-related apoptosis-inducing ligand
      (TRAIL)-induced apoptosis by inhibition of NF-kappaB activation.
AB  - TNF-related apoptosis-inducing ligand (TRAIL/Apo- 2L), a newly identified member
      of the TNF family promotes apoptosis by binding to the transmembrane receptors
      (TRAIL-R1/DR4 and TRAIL-R2/DR5). TRAIL known to activate NF-kappaB in number of
      tumor cells including A549 (wt p53) and NCI-H1299 (null p53) lung cancer cells
      exerts relatively selective cytotoxic affects to the human tumor cell lines
      without much effect on the normal cells. We set out to identify an agent that
      would sensitize lung cancer cells to TRAIL-induced apoptosis through inhibition
      of NF-kappaB activation. We found that triptolide, an oxygenated diterpene
      extracted and purified from the Chinese herb Tripterygium wilfordii sensitized
      A549 and NCI-H1299 cells to TRAIL-induced apoptosis through inhibition of NF
      kappaB activation. Pretreatment with MG132 which is a well-known NF-kappaB
      inhibitor by blocking degradation of IkappaBalpha also greatly sensitized lung
      cancer cells to TRAIL-induced apoptosis. Triptolide did not block DNA binding of
      NF-kappaB activated by TRAIL as in the case of TNF-alpha. It has been already
      proven that triptolide blocks transactivation of p65 which plays a key role in NF
      kappaB activation. These observations suggest that triptolide may be a
      potentially useful drug to enhance TRAIL-induced tumor killing in lung cancer.

PMID- 12526089
TI  - Overexpression of neurogenin1 induces neurite outgrowth in F11 neuroblastoma
      cells.
AB  - Neurogenin1 (Ngn1) is a basic helix-loop-helix (bHLH) transcription factor
      expressed in neuronal precursors in the developing nervous system. The function
      of Ngn1 in neurogenesis has been shown in various aspects. In this study, we
      investigated the neurogenic potential of Ngn1 using neuroblastoma cell line, F11,
      which could be induced to differentiate into neurons in the presence of cAMP. To
      investigate the expression of Ngn1, expression vectors for the full-length and
      the C- terminal deletion mutant of Ngn1 were constructed and their
      transactivation potential was verified using reporter gene containing the E-box
      sequence. Overexpression of the full-length Ngn1 induced neurite outgrowth in F11
      cells in the absence of cAMP. A C-terminal deletion mutant, Ngn1(1-197),
      inhibited neurite outgrowth induced by cAMP in F11 cells. These results indicate
      that the Ngn1 plays an important role in differentiation of neuroblastoma cells
      and the C terminus of Ngn1 is essential for the efficient differentiation.

PMID- 12526090
TI  - Interaction between chicken protein tyrosine phosphatase 1 (CPTP1)-like rat
      protein phosphatase 1 (PTP1) and p60(v-src) in v-src-transformed Rat-1
      fibroblasts.
AB  - CPTP1 is a nontransmembrane chicken protein tyrosine phosphatase having 92%
      sequence homology to the corresponding 321 amino acids of human protein tyrosine
      phosphatase 1B (HPTP1B). Using anti-CPTP1 antibody, we identified CPTP1-like rat
      PTP1 of 51 kDa in Rat-1 and v-src-transformed Rat-1 fibroblasts. Here we show
      that CPTP1-like rat PTP1 binds to p60(v-src) in vivo and CPTP1 also can associate
      with p60(v-src) in cell lysate of v-src- transformed Rat-1 fibroblasts.
      Interaction between HPTP1B-type PTPs, CPTP1-like rat PTP1 and CPTP1, and p60(v
      src) was reduced by vanadate treatment for 13 h due to down regulation of the
      protein level of p60(v-src) in vivo. Interestingly, CPTP1-like rat PTP1 was
      coimmunoprecipitated with a 70-kDa protein which has a possibility to be tyrosine
      phosphorylated by p60(v-src) in v-src-transformed Rat-1 fibroblasts. These
      results suggest that HPTP1B-type PTPs may play an important role in p60(src)
      dependent signal pathway in eucaryotic cells.

PMID- 12526091
TI  - Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism.
AB  - To determine whether the PPARalpha agonist fenofibrate regulates obesity and
      lipid metabolism with sexual dimorphism, we examined the effects of fenofibrate
      on body weight, white adipose tissue (WAT) mass, circulating lipids, and the
      expression of PPARalpha target genes in both sexes of high fat diet-fed C57BL/6J
      mice. Both sexes of mice fed a high-fat diet for 14 weeks exhibited increases in
      body weight, visceral WAT mass, as well as serum triglycerides and cholesterol,
      although these effects were more pronounced among males. Feeding a high fat diet
      supplemented with fenofibrate (0.05% w/w) reduced all of these effects
      significantly in males except serum cholesterol level. Females on a fenofibrate
      enriched high fat diet had reduced serum triglyceride levels, albeit to a smaller
      extent compared to males, but did not exhibit decreases in body weight, WAT mass,
      and serum cholesterol. Fenofibrate treatment resulted in hepatic induction of
      PPARalpha target genes encoding enzymes for fatty acid beta-oxidation, the
      magnitudes of which were much higher in males compared to females, as evidenced
      by results for acyl-CoA oxidase, a first enzyme of the beta-oxidation system.
      These results suggest that observed sexually dimorphic effects on body weight,
      WAT mass and serum lipids by fenofibrate may involve sexually related elements in
      the differential activation of PPARalpha.

PMID- 12526092
TI  - Deoxyhypusine synthase is phosphorylated by protein kinase C in vivo as well as
      in vitro.
AB  - Deoxyhypusine synthase catalyzes the first step in the posttranslational
      synthesis of an unusual amino acid, hypusine, in the eukaryotic translation
      initiation factor 5A (eIF-5A) precursor protein. We earlier observed that yeast
      recombinant deoxyhypusine synthase was phosphorylated by protein kinase C (PKC)
      in vitro (Kang and Chung, 1999) and the phosphorylation rate was synergistically
      increased to a 3.5-fold following treatment with phosphatidylserine
      (P.Ser)/diacylglycerol (DAG)/ Ca(2+), suggesting a possible involvement of PKC.
      We have extended study on the phosphorylation of deoxyhypusine synthase in vivo
      in different cell lines in order to define its role on the regulation of eIF5A in
      the cell. Deoxyhypusine synthase was found to be phosphorylated by endogenous
      kinases in CHO, NIH3T3, and chicken embryonic cells. The highest degree of
      phosphorylation was found in CHO cells. Moreover, phosphorylation of
      deoxyhypusine synthase in intact CHO cells was revealed and the expression of
      phosphorylated deoxyhypusine synthase was significantly diminished by diacyl
      ethylene glycol (DAEG), a PKC inhibitor, and enhanced by phorbol 12-myristate 13
      acetate (PMA) or Ca(2+)/DAG. Endogenous PKC in CHO cell and cell lysate was able
      to phosphorylate deoxyhypusine synthase and this modification is enhanced by PMA
      or Ca(2+) plus DAG. Close association of PKC with deoxyhypusine synthase in the
      CHO cells was evident in the immune coprecipitation and was PMA-, and
      Ca(2+)/phospholipid dependent. These results suggest that phosphorylation of
      deoxyhypusine synthase was PKC-dependent cellular event and open a path for
      possible regulation in the interaction with eIF5A precursor for hypusine
      synthesis.

PMID- 12526093
TI  - Improved immunodetection of human papillomavirus E7.
AB  - Human papillomavirus E7 (HPV E7) is a viral oncoprotein that plays an important
      role in cervical carcinogenesis through binding with retinoblastoma protein (Rb).
      Inactivation of Rb by E7 is necessary but not sufficient for cellular
      transformation, suggesting other protein-protein interactions are required for E7
      mediated cellular transformation aside from the interaction with Rb. However,
      studies on the oncogenic function of HPV E7 have been limited by its poor
      immunoreactivity. In this report, we show that the fixation of purified
      recombinant HPV E7 on blotted nitrocellulose membrane with glutaldehyde markedly
      enhanced the immunoreactivity of HPV E7 protein. Using HeLa and Caski cell lines
      which are infected with HPV 18 and HPV 16, respectively, we demonstrated that
      native HPV E7 proteins also could be detected by this method. These results
      therefore can provide the experimental conditions for detection of HPV E7
      proteins with greater sensitivity and may help to analyze E7 functions.

PMID- 12526094
TI  - Prevention of liver cancer: basic and clinical aspects.
AB  - Cancer prevention is a challenging project both in the basic and clinical
      medicine. In particular, prevention of liver cancer is the most urgent task in
      countries where the incidence of hepatitis virus- related liver cancer is rising.
      As reviewed in this article, liver cancer is going to be the first cancer that
      will be actually prevented by primary and secondary interventions. Even the
      improvement of absolute survival of the patients can be expected by successful
      prevention, as already demonstrated in a few clinical trials. Thus, prevention of
      liver cancer is promising to provide not only cost-effectiveness by morbidity
      reduction but also cost-benefit by mortality improvement.

PMID- 12526095
TI  - Comparative binding of antitumor drugs to DNA containing the telomere repeat
      sequence.
AB  - Telomeres are the ends of the linear chromosomes of eukaryotes and consist of
      tandem GT-rich repeats in telomere sequence i.e. 500-3000 repeats of 5'-TTAGGG-3'
      in human somatic cells, which are shortened gradually with age. The G-rich
      overhang of telomere sequence can adopt different intramolecular fold-backs and
      tetra-stranded DNA structures, in vitro, which inhibit telomerase activity. In
      this report, DNA binding agents to telomere sequence were studied novel
      therapeutic possibility to destabilize telomeric DNA sequences. Oligonucleotides
      containing the guanine repeats in human telomere sequence were synthesized and
      used for screening potential antitumor drugs. Telomeric DNA sequence was
      characterized using spectral measurements and CD spectroscopy. CD spectrum
      indicated that the double-stranded telomeric DNA is in a right-handed
      conformation. Polyacrylamide gel electrophoresis was performed for binding
      behaviors of antitumor compounds with telomeric DNA sequence. Drugs interacted
      with DNA sequence caused changes in the electrophoretic mobility and band
      intensity of the gels. Depending on the binding mode of the anticancer drugs,
      telomeric DNA sequence was differently recognized and the efficiency of cleavage
      of DNA varies in the bleomycin-treated samples under different conditions. DNA
      cleavage occurred at about 1% by the increments of 1 micromM bleomycin-Fe(III).
      These results imply that the stability of human telomere sequence is important in
      conjunction with the cancer treatment and aging process.

PMID- 12526096
TI  - Dual effect of oxidative stress on NF-kappakB activation in HeLa cells.
AB  - Reactive oxygen species (ROS) has been implicated as an inducer of NF-kappaB
      activity in numbers of cell types where exposure of cells to ROS such as H(2)O(2)
      leads to NF-kappaB activation. In contrast, exposure to oxidative stress in
      certain cell types induced reduction of tumor necrosis factor (TNF)- induced NF
      kappaB activation. And various thiol-modifying agents including gold compounds
      and cyclopentenone prostaglandins inhibit NF-kappaB activation by blocking
      IkappaB kinase (IKK). To understand such conflicting effect of oxidative stress
      on NF- kappakB activation, HeLa cells were incubated with H(2)O(2) or diamide and
      TNF-induced expression of NF-kappaB reporter gene was measured. NF-kappaB
      activation was significantly blocked by these oxidizing agents, and the
      inhibition was accompanied with reduced nuclear NF-kappaB and inappropriate
      cytosolic IkappaB degradation. H(2)O(2) and diamide also inhibited IKK activation
      in HeLa and RAW 264.7 cells stimulated with TNF and lipopolysaccharide,
      respectively, and directly blocked IKK activity in vitro. In cells treated with
      H(2)O(2) alone, nuclear NF-kappaB was induced after 2 h without detectable
      degradation of cytosolic IkappaBalphaa or activation of IKK. Our results suggest
      that ROS has a dual effect on NF-kappaB activation in the same HeLa cells: it
      inhibits acute IKK-mediated NF-kappakB activation induced by inflammatory
      signals, while longer-term exposure to ROS induces NF-kappaB activity through an
      IKK-independent pathway.

PMID- 12526097
TI  - Macrophage colony-stimulating factor promotes the survival of osteoclast
      precursors by up-regulating Bcl-X(L).
AB  - Macrophage colony-stimulating factor (M-CSF) is known as one of the factors
      essential for osteoclast development. In the present study, we examined effects
      of M-CSF on the apoptotic pathway of osteoclast precursors and their underlying
      molecular mechanisms. Osteoclast precursors underwent apoptosis in the absence of
      M-CSF, even in the presence of receptor activator of NF-kappakB ligand (RANKL).
      Active caspase-3 and -9 were detected in the osteoclast precursors and treatments
      of precursors with their specific inhibitors (Z-DEVD-FMK and Z-LEHD-FMK)
      decreased the apoptosis. M-CSF decreased apoptosis in a dose-dependent manner
      with decreasing in active caspases-3 and -9 levels and up-regulating Bcl-X(L).
      Those effects of M-CSF on inhibiting apoptosis of osteoclasts precursor by
      regulating anti-apoptotic signals was more effective when combined with RANKL.
      These results demonstrate that M-CSF acts as a survival factor for the osteoclast
      precursors. Furthermore, it is believed that the apoptosis of osteoclast
      precursors may be involved in the activation of caspase-9 and that M-CSF may
      promote their survival through Bcl-X(L)-induced inhibition of caspase-9
      activation.

PMID- 12526098
TI  - Osteoprotegerin is present on the membrane of osteoclasts isolated from mouse
      long bones.
AB  - Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor
      superfamily, is known to inhibit osteoclastogenesis by acting as a soluble decoy
      receptor for the receptor activator of NF-kappaB ligand (RANKL). We report the
      presence of OPG on the membrane of osteoclasts and the possibility of the direct
      action of OPG on them. Highly pure osteoclast precursors were isolated from mouse
      long bones and induced to differentiate into mature osteoclasts by M-CSF and
      soluble RANKL (sRANKL). The presence of OPG on the membrane of these cells was
      confirmed by western blotting and immunostaining. Furthermore, sRANKL was found
      to be bound to the OPG on the osteoclast precursors. These results suggest that
      OPG might have a new role during the differentiation of osteoclasts beyond its
      role as a soluble decoy receptor. The mechanism of the existence of OPG on
      osteoclast precursors remains to be found.

PMID- 12526099
TI  - Retinoic acid inhibits inducible nitric oxide synthase expression in 3T3-L1
      adipocytes.
AB  - The present study was undertaken to explore whether retinoids, which are known to
      have immunomodulatory actions, could attenuate tumor necrosis factor-alpha (TNF)
      stimulated inducible nitric oxide synthase (iNOS) expression in 3T3-L1
      adipocytes. Adipocytes incubated with TNF induced dose- and time-dependent
      accumulation of nitrite in the culture medium through the iNOS induction as
      confirmed by Western blotting. Treatment of cells with TNF in the presence of all
      trans-retinoic acid (RA) significantly decreased their ability to produce nitrite
      and iNOS induction. Both 13-cis- and all- trans-RA-induced suppression was dose
      dependent, and all-trans-RA was somewhat potent than 13-cis-RA. The inhibitory
      effect of RA on TNF-induced iNOS induction was reversible, completely recovered
      after 2 days, and was exerted through the inhibition of NF-kappaB activation. TNF
      also suppressed the lipoprotein lipase (LPL) activity of 3T3-L1 adipocytes. RA
      could not reverse the TNF- induced LPL suppression at RA levels causing near
      complete inhibition of the TNF-induced NO production. These results indicate that
      RAs attenuate iNOS expression reversibly in TNF-stimulated 3T3-L1 adipocytes, and
      that the TNF-induced LPL suppression is not the result of NO overproduction.

PMID- 12526100
TI  - Changes in expression of cell cycle regulators after G1 progression upon
      repetitive thioacetamide treatment in rat liver.
AB  - Repetitive low dose thioacetamide (TA) treatment of hepatocytes was found to
      induce cells in G2 arrest. In the present study, an attempt was made to
      investigate alterations in expression of cell cycle regulators after G1
      progression in the same repetitive low dose TA treated hepatocytes system and to
      define the determinators involved in G2 arrest. TA was daily administered
      intraperitoneally, with a dose of 50 mg/kg for 7 days. Expression levels of
      cyclin E and CDK2 were similar, increased at day 1 and reached a peak at day 2.
      And they recycled from day 3 reaching a second peak at day 5. Expression level of
      cyclin A was similar to p27(Kip1) and p57(Kip2) but not to CDK2 and increased to
      a peak level at day 2. Expression levels of cyclin B1 and cdc2 were similar
      although the cyclin B1 level was generally low, decreased from day 1 to basal
      levels at day 3 and persisted at a low level till day 7. The expression level of
      cyclin G1 was similar to p53 that peaked at day 3 and again at day 6 elevated
      over basal level. BrdU-labeled hepatocytic nuclei increased from 12 h, reached a
      peak at day 2, then decreased, and were not detectable from day 6. The number of
      PCNA-labeled nuclei increased immediately, peaked at day 2, and maintained till
      day 7. These results suggest that G2 arrest induced by repeated TA treatment
      might be p53-dependent, via activation of cyclin G1, rather than inhibition of
      cyclin B1- cdc2 complex, and inhibitors holding S phase progression might be
      p27(Kip1) and p57(Kip2).

PMID- 12526101
TI  - Inhibition of BETA2/NeuroD by Id2.
AB  - Id (Inhibitor of Differentiation) proteins belong to a family of transcriptional
      modulators that are characterized by a helix loop helix (HLH) region but lack the
      basic amino acid domain. Id proteins are known to interact with basic helix-loop
      helix (bHLH) transcription factors and function as their negative regulators. The
      negative role of Id proteins has been well demonstrated in muscle development and
      some in neuronal cells. In this study, we investigated the effect of Id on the
      function of BETA2/NeuroD, a bHLH transcription factor responsible for neuron and
      endocrine cell specific gene expression. cDNAs of several Id isoforms were
      isolated by yeast two-hybrid system using the bHLH domain of E47, a ubiquitous
      bHLH partner as a bait. Id proteins expressed in COS M6 cells, were found in both
      cytosolic and nuclear fractions. Electrophoretic mobility shift assay showed that
      coexpression of Id2 proteins inhibited BETA2/ NeuroD binding to its target
      sequence, E-box. Id2 inhibited E-box mediated gene expression in a dose dependent
      manner in BETA2/NeuroD expressing HIT cells. Id coexpressed with BETA2/NeuroD in
      HeLa cells, inhibited the stimulatory activity of BETA2/NeuroD. These results
      suggest that Id proteins may negatively regulate tissue specific gene expression
      induced by BETA2/NeuroD in neuroendocrine cells and the inhibitory role of Id
      proteins during differentiation may be conserved in various tissues.

PMID- 12526102
TI  - Proteomic analysis of the cellular proteins induced by adaptive concentrations of
      hydrogen peroxide in human U937 cells.
AB  - When cells are first exposed to low levels of oxidative stress, they develop a
      resistance to a subsequent challenge of the same stress, even at higher levels.
      Although some protein(s) induced by oxidative stress likely mediated this
      adaptive response, the nature of these proteins is unknown. In this study, the
      total proteins extracted from human U937 leukemia cells exposed to 50 micromM
      H(2)O(2) for 24 h to induce an optimal protective response were analyzed by two
      dimensional polyacrylamide gel electrophoresis. H(2)O(2) treatment induced
      elevation of level of 34 protein spots. An analysis of these spots by a matrix
      associated laser desorption/ionization time-of-flight mass spectrometry
      identified 28 of the H(2)O(2)-induced proteins. These include proteins involved
      in energy metabolism, translation and RNA processing, chaperoning or mediating
      protein folding, cellular signaling, and redox regulation, as well as a
      mitochondrial channel component, and an actin-bundling protein. Therefore, it
      appears that the cellular adaptation to oxidative stress is a complex process,
      and is accompanied by a modulation of diverse cellular functions.

PMID- 12526103
TI  - C/EBP binding activity to site F of the rat GLUT2 glucose transporter gene
      promoter is attenuated by c-Jun in vitro.
AB  - The expression of the GLUT2 glucose transporter gene in liver is suppressed in
      cultured hepatoma cell lines and primary cultured hepatocytes. Earlier report
      showed that CCAAT/enhancer binding protein (C/EBP) regulates the promoter
      activity of the rat GLUT2 glucose transporter gene in liver cells. C/EBPalpha and
      C/EBPbeta activated the promoter activity by binding to at least two regions of
      the promoter and one of the C/EBP binding sites, named as site F, also has the AP
      1 binding consensus. In this study, we investigated whether the AP-1 can
      influence on C/EBP binding to this site. The addition of recombinant c-Jun
      protein with liver extract caused the attenuation of C/EBP binding to site F with
      the appearance of a new shifted band. The shifted band was competed out with the
      addition of unlabeled AP-1 consensus oligonucleotide, indicating that c-Jun also
      can bind to site F. Another C/EBP site on GLUT2 promoter, site H, did not bind AP
      1. Analysis of the DNA-protein complex revealed that C/EBP and c-Jun bind to site
      F in mutually exclusive manner rather than form heterodimeric complex with each
      other. From these results, it is suggested that the transcriptional activation of
      C/EBP may be influenced by c-Jun protein in certain status of the liver cells,
      such as acute phase response, as well as hepatocarcinogenesis.

PMID- 12526104
TI  - Effects of Val34Leu and Val35Leu polymorphism on the enzyme activity of the
      coagulation factor XIII-A.
AB  - Change in fibrin stabilizing activity of factor XIII A subunit (FXIII-A) caused
      by a specific mutation, Val34Leu, is recently implicated to incidences of
      pathophysiology of thrombosis. In an effort to understand the effect of Val34Leu
      on enhanced catalytic role of FXIII-A, wild type human factor XIII A (HFXIII-A)
      and mutant HFXIII-A: HFXIII-A (V34L), HFXIII-A (V35L) and HFXIII-A (V34L/V35L)
      cDNA were expressed in E.coli system where the purified recombinant FXIII-A
      (gammaFXIII-A) showed a similar specific transglutaminase activity comparable to
      the human native FXIII-A from platelet. Using these gammaFXIII-A mutants, the
      activation kinetics by thrombin and the enzymatic properties of the activated
      gammaFXIII-A were characterized. gammaFXIII-A (V34L) and gammaFXIII-A (V34L/V35L)
      mutants were activated by thrombin much faster than those of wild type
      gammagFXIII-A and V35L variant. However, the activated gammaFXIII-A and mutants
      showed the identical catalytic efficiency as measured by in vitro assay. These
      results suggest that ready activation caused by a specific mutation of
      neighboring thrombin cleavage site(s) in the activation peptide of FXIII-A like
      V34L resulted in the real-time amount of the activated factor XIII-A that could
      influence the outcome of fibrin stabilization in vivo such as alpha2-plasmin
      inhibitor crosslinking to fibrin, a reaction known to be dependent on the initial
      concentration of active factor-XIII-A.

PMID- 12526105
TI  - Heart failure. A growing problem with age.

PMID- 12526106
TI  - Health tips. Safe snow shoveling.

PMID- 12526107
TI  - New treatment for clogged coronary arteries.

PMID- 12526108
TI  - Plantar fasciitis. Heel pain that heals...eventually.

PMID- 12526109
TI  - Sexuality after cancer. Precautions, possibilities.

PMID- 12526110
TI  - Aspirin. New uses for an old standby.

PMID- 12526111
TI  - Second opinion. I've had trouble sleeping lately because I tend to get cramps in
      my calf muscles and feet at night. What causes these cramps? What can I do about
      them?

PMID- 12526112
TI  - Second opinion. I have benign prostatic hyperplasia. The drug my doctor
      prescribed has helped somewhat, but I'm still making a lot of trips to the
      bathroom at night. Short of surgery, are there any new approaches to managing
      this condition that might be more helpful?

PMID- 12526113
TI  - Current awareness on yeast.

PMID- 12526114
TI  - Proceedings of the Summit Meeting on Breast Cancer Among African American Women.
      Washington, DC, USA. September 8-10, 2002.

PMID- 12526115
TI  - Retraction.

PMID- 12526116
TI  - Issue in memory of Ettore Biocca.

PMID- 12526117
TI  - Chlamydiae in cattle and pigs and the zoonotic potential. Abstracts from the 2nd
      workshop, 24-25 September 2002 in Jena, Germany.

PMID- 12526118
TI  - John Jacquez memorial volume.

PMID- 12526119
TI  - Serono Symposia International Conference. Robert G. Edwards at 75. Venezia Lido,
      Italy, 2-3 October 2000.

PMID- 12526120
TI  - Proceedings and abstracts of the 2nd Hungarian Conference of Mycology. 29-31 May
      2002, Szeged, Hungary.

PMID- 12526121
TI  - Abstracts from the Bone and Tooth Society annual meeting. 24-26 June 2002,
      Cardiff, United Kingdom.

PMID- 12526122
TI  - Recent Advances in Nutritional Sciences and Critical Reviews from the Journal of
      Nutrition volumes 130-132, 2000-2002.

PMID- 12526123
TI  - Abstracts of the 14th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
      Therapeutics. Frankfurt, Germany, 19-22 November 2002.

PMID- 12526124
TI  - Oral health policies. American Academy of Pediatric Dentistry.

PMID- 12526125
TI  - Guidelines. American Academy of Pediatric Dentistry.

PMID- 12526126
TI  - De disappearing D-dimer.

PMID- 12526127
TI  - Abstracts of the 6th Aachen Glaucoma Symposium 2002, Germany.

PMID- 12526128
TI  - Medical mistakes, errors in judgment, and personal awareness.

PMID- 12526129
TI  - Anhydrous ammonia eye injuries associated with illicit methamphetamine
      production.

PMID- 12526130
TI  - Abstracts for the Xth World Congress of Psychiatric Genetics. Brussels, Belgium,
      9-13 October 2002.

PMID- 12526131
TI  - Acute fatal toxic myocarditis after black widow spider envenomation.

PMID- 12526132
TI  - Physician's knowledge of and attitudes toward a domestic violence mandatory
      reporting law.

PMID- 12526133
TI  - Abstracts of the XXII Congress of the Polish Physiological Society. 4-7 September
      2002, Bydgoszcz, Poland.

PMID- 12526134
TI  - Reaffirmed cost-effectiveness of poison centers.

PMID- 12526135
TI  - Medicare and durable medical equipment.
AB  - Medicare coverage of wheelchairs, hospital beds and other durable medical
      equipment (DME) is a major source of confusion for people with Medicare, their
      families and the professionals who work with them. Yet, consumer publications
      rarely touch on it. In this brief we offer an overview of DME coverage issues and
      payment policies, including potential costs for consumers and their rights to
      appeal denials of payment.

PMID- 12526136
TI  - Abstracts of the 6th International Congress of the Immunology of Diabetes Society
      and American Diabetes Association Research Symposium. October 3-6, 2002, Copper
      Mountain, Colorado, USA.

PMID- 12526137
TI  - Society of Critical Care Medicine 32nd Critical Care Congress. San Antonio,
      Texas, USA. January 28-February 2, 2003. Abstracts.

PMID- 12526139
TI  - [96th French Congress of Urology. Paris, France, 20-23 November 2002. Abstracts].

PMID- 12526138
TI  - Cumulative 25 year index, volumes 1-25, 1978-2002.

PMID- 12526140
TI  - Stroke: diagnostic and therapeutic pathways. Abstracts of the 11th National
      Congress of the Italian Interdisciplinary Neurovascular Society (SINV). Florence,
      Italy, 6-7 December 2002.

PMID- 12526141
TI  - Abstracts of the 1st Asian Chapter Meeting--International Society for Peritoneal
      Dialysis. Hong Kong, December 13-15, 2002.

PMID- 12526142
TI  - Abstracts from the 13th International Symposium on Amyotrophic Lateral
      Sclerosis/Motor Neuron Diseases. Melbourne, Australia, 17-19 November 2002.

PMID- 12526143
TI  - [Abstracts of the 11th annual meeting of the Ophthalmologists Society of Saxony
      Thuringia. 2-3 November 2002, Ergurt].

PMID- 12526144
TI  - [Stimulant drugs in neurofibromatosis type 1 and attention deficit disorder].

PMID- 12526146
TI  - Cancer. Easing the treatment.

PMID- 12526145
TI  - Molecular mechanisms and stem cell therapy.

PMID- 12526147
TI  - Conflict of laws.

PMID- 12526148
TI  - Expansion of nurse anesthesia educational programs: where are the barriers?
AB  - CRNAs have been a major contributor to direct patient anesthesia care for more
      than 100 years. All indicators suggest a greater need for nurse anesthetist
      services in the future. Our ability to meet this increased demand will depend on
      wise decisions in accreditation and professional agendas and support of all CRNAs
      in this critical issue. As stated by AANA Past President Linda Williams, CRNA,
      JD, students represent only 10% of our membership but they represent 100% of our
      future. Let's unite all forces to secure a future in which CRNAs will be
      indispensable healthcare providers throughout the 21st century.

PMID- 12526149
TI  - The effects of spinal anesthesia vs epidural anesthesia on 3 potential
      postoperative complications: pain, urinary retention, and mobility following
      inguinal herniorrhaphy.
AB  - This study was conducted to determine the effects of spinal (n = 113) vs epidural
      (n = 31) anesthetic techniques on 3 common postoperative complications: pain,
      urinary retention, and mobility for patients undergoing inguinal herniorrhaphy.
      The study design was a retrospective chart review. Data were collected on 144
      subjects who underwent herniorrhaphy between January 1 and December 31, 1999, had
      an ASA classification of I to III, and were older than 18 years. The local
      anesthetics used to provide spinal anesthesia were 5% lidocaine, 0.75%
      bupivacaine, and 1% tetracaine solutions. The anesthetics used to provide
      epidural anesthesia were a solution of 2% lidocaine with epinephrine or 3%
      chloroprocaine with epinephrine. Results revealed that pain was not significantly
      different between the 2 anesthetic groups (P = .65); however, subjects in the
      epidural anesthesia group were able to ambulate (P = .008) and void (P = .02)
      sooner than subjects in the spinal anesthesia group. This study demonstrates that
      epidural anesthesia results in less urinary retention and earlier mobility than
      spinal anesthesia in men undergoing inguinal herniorrhaphy. Minimizing
      postoperative complications is essential in order for the nurse anesthetist to
      provide a satisfactory anesthetic experience. This study's findings suggest that
      epidural anesthesia optimizes recovery for the patient undergoing inguinal
      herniorrhaphy.

PMID- 12526150
TI  - The effect of spinal introducer needle use on postoperative back pain.
AB  - Postdural puncture back pain has a reported incidence ranging from 2% to 29%
      following the administration of a spinal anesthetic. The purpose of this
      investigation was to compare the back pain and patient satisfaction scores after
      the administration of a spinal anesthetic with or without the use of an 18-gauge
      introducer needle. Eighty-four men and women were randomly assigned to either
      control or experimental groups; 67 were included in data analysis. The control
      group (n = 33) received spinal anesthesia using only a spinal needle, while the
      experimental group (n = 34) received spinal anesthesia using an introducer needle
      to guide the placement of the spinal needle. Pain measurements were measured
      using a 100-mm Visual Analogue Scale upon arrival in the postanesthesia care
      unit, and at 24, 48, and 72 hours postoperatively. Patient satisfaction scores
      were evaluated using a 1 to 5 Lickert scale. No significant differences were
      found between groups concerning back pain or patient satisfaction scores upon
      discharge from the postanesthesia care unit, nor at 24, 48, and 72 hours
      postoperatively. However, a significant increase in the number of redirections
      between groups was observed in the nonintroducer group; despite this, back pain
      and patient satisfaction scores were not affected.

PMID- 12526151
TI  - Massive subcutaneous emphysema and hypercarbia: complications of carbon dioxide
      absorption during extraperitoneal and intraperitoneal laparoscopic surgery--case
      studies.
AB  - The laparoscopic approach to surgery is being used with greater frequency as our
      healthcare system continues to strive for shorter hospital stays and improved
      postoperative patient recovery times. However, laparoscopy is not without
      potential complications. This article presents 2 patient case studies. The cases
      differ in surgical technique. One patient's laparoscopic surgery involved an
      extraperitoneal approach. The second patient's surgery involved an
      intraperitoneal approach. Massive subcutaneous emphysema developed in both
      patients. The phenomenon of subcutaneous emphysema associated with laparoscopic
      surgery will be defined and discussed.

PMID- 12526152
TI  - Nurse anesthesia research: a follow-up study.
AB  - We describe a follow-up study comparing nurse anesthesia research in the 1990s
      with findings of a previous study. Research reported in the AANA journal in 1995
      and 1996 (n = 38 studies) was compared with the earlier description of research
      from 1985-1986 (n = 18) and 1975-1976 (n = 14) periods. The amount of research
      published in the Journal has increased steadily, with a stable focus on clinical
      practice. In addition, there has been an increase in educational and safety
      related research reported. In an attempt to locate research published in other
      nursing and medical journals, we found and reviewed additional articles (n = 28)
      authored or coauthored by CRNAs during the 1995-1996 period. By the 1990s, all
      studies demonstrated at least 1 indicator of theoretical orientation. Convenience
      samples of hospitalized patients were the most common type of sample. As in the
      earlier study, there was minimal reporting on reliability and validity of data
      and the psychometric evaluation of instruments. Recommendations include increased
      emphasis on methodological studies, multisite studies, programs of research, and
      collaboration among CRNAs, nurses in other specialties, and people in other
      disciplines.

PMID- 12526153
TI  - Assessing the authenticity of the human simulation experience in anesthesiology.
AB  - There is an absence of systematic study regarding the authenticity of the
      simulation experience in anesthesia except for bias prone "participant
      perception" assessments. Forty-two senior level graduate nurse anesthesia
      students were videotaped as they were exposed to short (20-30 minutes) but
      intense simulated crisis situations. Three observers with intimate knowledge of
      the operating room (OR) evaluated the films using a pilot-tested authenticity
      tool. Agreement among the observers was satisfactory. k statistics ranged from
      .75-.90 on the various measures (kappa > .70 is considered good). Concerns
      abounded regarding a failure to convincingly mirror the OR "culture." A high
      degree of "anticipation" that something was about to go wrong was evident. The
      sense of being in the "hot seat" was ubiquitous; hypervigilance of monitors
      exacerbated the unrealism. Rapid, mechanical, and anxious behavior in the
      anesthesia providers seemed to be excessive. Reviewers rated the case scenarios
      themselves as extremely realistic and of high educational value. There was
      concern that the brevity of the scenarios did not reflect the realities of
      patient care during procedures of average length. Simulation is likely of maximal
      benefit if the participant perceives it as legitimate and authentic. Our study
      indicates the authenticity of anesthesia simulation is in evolution with much
      potential for improvement.

PMID- 12526154
TI  - AANA journal course. Update for nurse anesthetists. Gender and pain.
AB  - A major responsibility of nurse anesthetists caring for patients is the provision
      of adequate pain relief. A growing body of evidence in the literature suggests
      that gender of the provider and gender of the patient may affect the clinical
      management of pain. The different socialization processes of children has been
      theorized to influence how, as adults, individuals perceive and express pain. The
      willingness of females to express their discomfort has led to the perception that
      females are more emotional and expressive than males; this perception has led
      investigators to note that females may be at a disadvantage in the treatment of
      pain. Recently recognized disparities between the sexes in their response to
      antidepressants, certain opioids, and inhalation agents, as well as the
      identification of gender distributions for certain diseases, has heightened
      awareness among the scientific community of gender influences and gender
      differences that were not evident in the past. Awareness among nurse anesthetists
      of these differences, as well as the possible influence of gender, is critical to
      individualize anesthetic management and to minimize the potential for gender bias
      in providing pain management.

PMID- 12526155
TI  - List of recognized educational programs by Council on Accreditation of Nurse
      Anesthesia Educational Programs.

PMID- 12526156
TI  - Use of the herpes simplex viral genome to construct gene therapy vectors.

PMID- 12526157
TI  - Construction of multiply disabled herpes simplex viral vectors for gene delivery
      to the nervous system.

PMID- 12526158
TI  - Improved HSV-1 amplicon packaging system using ICP27-deleted, oversized HSV-1 BAC
      DNA.

PMID- 12526159
TI  - Herpes simplex amplicon vectors.

PMID- 12526160
TI  - Strategies to adapt adenoviral vectors for targeted delivery.

PMID- 12526161
TI  - Use of recombinant adenovirus for gene transfer into the rat brain. Evaluation of
      gene transfer efficiency, toxicity, and inflammatory and immune reactions.

PMID- 12526162
TI  - Generation of adenovirus vectors devoid of all viral genes by recombination
      between inverted repeats.

PMID- 12526163
TI  - Packaging cell lines for generating replication-defective and gutted adenoviral
      vectors.

PMID- 12526164
TI  - Improving the transcriptional regulation of genes delivered by adenovirus
      vectors.

PMID- 12526166
TI  - Development and optimization of adeno-associated virus vector transfer into the
      central nervous system.

PMID- 12526165
TI  - Targeted integration by adeno-associated virus.

PMID- 12526167
TI  - A method for helper virus-free production of adeno-associated virus vectors.

PMID- 12526168
TI  - Novel tools for production and purification of recombinant adeno-associated viral
      vectors.

PMID- 12526169
TI  - Recombinant adeno-associated viral vector types 4 and 5. Preparation and
      application for CNS gene transfer.

PMID- 12526170
TI  - Trans-splicing vectors expand the packaging limits of adeno-associated virus for
      gene therapy applications.

PMID- 12526171
TI  - Generation of retroviral packaging and producer cell lines for large-scale vector
      production with improved safety and titer.

PMID- 12526172
TI  - An ecdysone-inducible expression system for use with retroviruses.

PMID- 12526173
TI  - In vivo infection of mice by replication-competent MLV-based retroviral vectors.

PMID- 12526174
TI  - Development of simian retroviral vectors for gene delivery.

PMID- 12526175
TI  - Self-inactivating lentiviral vectors and a sensitive Cre-loxP reporter system.

PMID- 12526176
TI  - Lentiviral vectors for gene transfer to the central nervous system. Applications
      in lysosomal storage disease animal models.

PMID- 12526177
TI  - A highly efficient gene delivery system derived from feline immunodeficiency
      virus (FIV).

PMID- 12526178
TI  - A multigene lentiviral vector system based on differential splicing.

PMID- 12526179
TI  - Production of trans-lentiviral vector with predictable safety.

PMID- 12526180
TI  - Human immunodeficiency virus type 1-based vectors for gene delivery to human
      hematopoietic stem cells.

PMID- 12526181
TI  - Semliki Forest virus vectors for gene transfer.

PMID- 12526182
TI  - Semliki Forest virus (SFV) vectors in neurobiology and gene therapy.

PMID- 12526183
TI  - Semliki Forest virus vectors for large-scale production of recombinant proteins.

PMID- 12526184
TI  - Development of foamy virus vectors.

PMID- 12526185
TI  - Poxviral/retroviral chimeric vectors allow cytoplasmic production of transducing
      defective retroviral particles.

PMID- 12526186
TI  - Diagnosis and treatment of worker-related musculoskeletal disorders of the upper
      extremity.

PMID- 12526187
TI  - Office managers--caretakers of the dental practice.

PMID- 12526188
TI  - Closing diastemas and creating artificial gingiva with polymer ceramics.
AB  - A 40-year-old male patient elected orthodontic correction of his crowded anterior
      teeth, leaving multiple root exposures and spacing in the papilla areas.
      Connective tissue surgery did not satisfy the patient's expectations and led him
      to seek alternative treatments. An innovative technique was developed to achieve
      root coverage and fill-in spaces in the papilla areas. This noninvasive technique
      used a polymer ceramic material that was bonded to the crown and root surface of
      the individual teeth. The veneer restorations were inserted on the teeth as a
      solid unit, then separated into individual units. Clinically, the hygiene, which
      has been monitored since the placement of the restorations 24 months ago, has
      been satisfactory. This case illustrates an attenuation of a previously described
      noninvasive laboratory technique to close spaces between teeth. This conservative
      method can be used to cover denuded root surfaces that may exhibit sensitivity.
      Although the treatment has been successful for the short-term, the results are
      promising and deserve further case-controlled clinical assessment.

PMID- 12526190
TI  - Periodontal plastic surgery procedures: subepithelial connective tissue graft for
      root coverage.

PMID- 12526189
TI  - Osteoporosis: a review and its dental implications.
AB  - Osteoporosis is a disease that affects primarily women, but can also occur in
      men. It is characterized by a loss of bone mineral density (BMD), and often
      culminates in a fracture of the hip, wrist, and/or vertebrae. The diagnosis of
      osteoporosis is often made by using bone density measurements. They are often
      expressed in relative terms (T-scores and Z-scores); the Z-score is the number of
      standard deviations from the age-matched average value of healthy women. A low Z
      score indicates the bone density is lower than it should be for a patient's age
      and sex. Osteoporosis is defined as a BMD loss of 2.5 standard deviations or more
      below the established mean. Osteoporosis can be treated by a variety of methods,
      the most common being the use of estrogen, with or without progestin or
      progesterone. The use of estrogen alone is referred to as estrogen replacement
      therapy (ERT), and the combination hormone replacement therapy (HRT). Other drugs
      used in the treatment of osteoporosis are the selective estrogen receptor
      modulators (SERMs) and the bisphosphonates. The SERMs appear to offer many of the
      positive benefits of estrogen with fewer adverse effects on the breast or uterus.
      Recently, a randomized, double blind study of nearly 3,000 women found no overall
      benefit in reducing heart disease for those taking estrogen. In fact, in the
      first year of estrogen use, heart disease was higher in this group than in those
      taking placebo. The relationship between systemic BMD and periodontal status has
      been investigated. In some patients, there is a correlation between a decrease of
      mandibular bone mass and tooth loss. In others, there is no such correlation.
      Those postmenopausal women taking HRT had greater tooth retention and a reduced
      likelihood of edentulism. A recent study has found no correlation between
      clinical attachment levels and the BMD of the lumbar spine. Many possible factors
      contribute to the development of osteoporosis and periodontal diseases. It is
      difficult to establish a direct correlation between tooth loss, bone loss, and
      loss of attachment resulting from periodontitis and decreased BMD associated with
      osteoporosis, but studies are ongoing.

PMID- 12526191
TI  - Bovine-derived bone protein extract in the treatment of mandibular Class II
      furcations.
AB  - This study was an initial evaluation of the use of a bovine-derived bone protein
      (BP) extract that contains various growth factors combined with decalcified
      freeze-dried bone allograft (DFDBA) as regenerative treatment for class II
      mandibular furcations. Twenty-five patients were divided into 5 groups according
      to the dosage of BP present per mg of DFDBA to be grafted: (1) 0.00 microgram/mg,
      (2) 3.13 micrograms/mg, (3) 6.25 micrograms/mg, (4) 12.5 micrograms/mg, and (5)
      25.0 micrograms/mg. Surgical exploration of the furcation defects was performed
      followed by grafting with BP/DFDBA. Results at 6 months showed that attachment
      gain in the treated furcation areas was greatest in Groups 4 and 5, suggesting
      that BP has the potential to increase the effects of DFDBA in gaining clinical
      attachment in mandibular class II furcations.

PMID- 12526192
TI  - MagicFil: a colorful kiddie compomer.

PMID- 12526193
TI  - [Proterozoic history and present state of cyanobacteria].
AB  - The paper delves into the main regularities of the distribution of fossil
      microorganisms in Precambrian rocks, beginning from the Archean Eon about 3.5
      billion years ago and ending in the Cambrian Period about 0.5 billion years ago.
      The paper analyzes facial peculiarities in the lateral differentiation of
      microfossils in Proterozoic basins and the main stages of temporal changes in
      fossil cyanobacterial communities, which are based on the irreversible succession
      of physicochemical conditions on the Earth and the evolution of eukaryotic
      microorganisms and their incorporation into prokaryotic ecosystems. To gain
      insight into Proterozoic fossil records, modern stratified cyanobacterial mats
      built up from layers of prokaryotes are considered. The analysis of
      phosphatization, carbonatization, and silification processes in modern algal
      bacterial communities suggests that analogous processes took place in Proterozoic
      microbiotas. A comparison of modern and Precambrian living forms confirms the
      inference that cyanobacterial communities are very conservative and have changed
      insignificantly both morphologically and physiologically during the past two
      billion years.

PMID- 12526194
TI  - [Methanotrophic bacteria of acid sphagnum bogs].
AB  - Acid sphagnum bogs cover a considerable part of the territory of Russia and are
      an important natural source of biogenic methane, which is formed in their
      anaerobic layers. A considerable portion of this methane is consumed in the
      aerobic part of the bog profile by acidophilic methanotrophic bacteria, which
      comprise the methane filter of sphagnum bogs and decrease CH4 emission to the
      atmosphere. For a long time, these bacteria escaped isolation, which became
      possible only after the elucidation of the optimal conditions of their
      functioning in situ: pH 4.5 to 5.5; temperature, from 15 to 20 degrees C; and low
      salt concentration in the solution. Reproduction of these conditions and
      rejection of earlier used media with a high content of biogenic elements allowed
      methanotrophic bacteria of two new genera and species--Methylocella palustris and
      Methylocapsa acidophila--to be isolated from the peat of sphagnum bogs of the
      northern part of European Russia and West Siberia. These bacteria are well
      adapted to the conditions in cold, acid, oligotrophic sphagnum bogs. They grow in
      a pH range of 4.2-7.5 with an optimum at 5.0-5.5, prefer moderate temperatures
      (15-25 degrees C) and media with a low content of mineral salts (200-500 mg/l),
      and are capable of active nitrogen fixation. Design of fluorescently labeled 16S
      rRNA-targeted oligonucleotide probes for the detection of Methylocella palustris
      and Methylocapsa acidophila and their application to the analysis of sphagnum
      peat samples showed that these bacteria represent dominant populations of
      methanotrophs with a density of 10(5)-10(6) cells/g peat. In addition to
      Methylocella and Methylocapsa populations, one more abundant population of
      methanotrophs was revealed (10(6) cells/g peat), which were phylogenetically
      close to the genus Methylocystis.

PMID- 12526195
TI  - [The enzyme of carbon metabolism in the thermotolerant sulfobacillus strain K1].
AB  - To determine enzymatic activities in the thermotolerant strain K1 (formerly
      "Sulfobacillus thermosulfidooxidans subsp. thermotolerans"), it was grown in a
      mineral medium with (1) thiosulfate and Fe2+ or pyrite (autotrophic conditions),
      (2) Fe2+, thiosulfate, and yeast extract or glucose (mixotrophic conditions), and
      (3) yeast extract (heterotrophic conditions). Cells grown mixo-, hetero-, and
      autotrophically were found to contain enzymes of the tricarboxylic acid (TCA)
      cycle, as well as malate synthase, an enzyme of the glyoxylate cycle. Cells grown
      organotrophically in a medium with yeast extract exhibited the activity of the
      key enzymes of the Embden-Meyerhof-Parnas and Entner-Doudoroff pathways. An
      increased content of carbon dioxide (up to 5 vol%) in the auto- and mixotrophic
      media enhanced the activity of the enzymes involved in the terminal reactions of
      the TCA cycle and the enzymes of the pentose phosphate pathway. Carbon dioxide
      was fixed in the Calvin cycle. The highest activity of ribulose bisphosphate
      carboxylase was detected in cells grown autotrophically at the atmospheric
      content of CO2 in the air used for aeration of the growth medium. The activities
      of pyruvate carboxylase, phosphoenolpyruvate carboxylase, phosphoenolpyruvate
      carboxykinase, and phosphoenolpyruvate carboxytransphosphorylase decreased with
      the increasing content of CO2 in the medium.

PMID- 12526196
TI  - [A comparative study of the isocitrate dehydrogenases of Chlorobium limicola
      forma Chlorobium thiosulfatophilum and Rhodopseudomonas palustris].
AB  - The carboxylation of 2-oxoglutarate in the reductive tricarboxylic acid cycle in
      the obligate photolithotroph Chlorobium limicola forma thiosulfatophilum and the
      oxidation of isocitrate in the tricarboxylic acid cycle in the photoheterotroph
      Rhodopseudomonas palustris are catalyzed by isocitrate dehydrogenases. A
      comparative study of these enzymes isolated from the two bacteria showed that
      they virtually do not differ in the enzymatic and kinetic properties.

PMID- 12526197
TI  - [The effect of sodium azide on the thermotolerance of the yeast Saccharomyces
      cerevisiae and Candida albicans].
AB  - The addition of sodium azide (a mitochondrial inhibitor) at a concentration of
      0.15 mM to glucosegrown Saccharomyces cerevisiae or Candida albicans cells before
      exposing them to heat shock increased cell survival. At higher concentrations of
      azide, its protective effect on glucose-grown cells decreased. Furthermore,
      azide, even at low concentrations, diminished the thermotolerance of galactose
      grown yeast cells. It is suggested that azide exerts a protective effect on the
      thermotolerance of yeast cells when their energy requirements are met by the
      fermentation of glucose. However, when cells obtain energy through respiratory
      metabolism, the azide inhibition of mitochondria enhances damage inflicted on the
      cells by heat shock.

PMID- 12526198
TI  - [The biosynthesis of low-molecular-weight nitrogen-containing secondary
      metabolite-alkaloids by the resident strains of Penicillium chrysogenum and
      Penicillium expansum isolated on the board of the Mir space station ].
AB  - The analysis of the absorption spectra of the low-molecular-weight nitrogen
      containing secondary metabolites--alkaloids--of 4 Penicillium chrysogenum strains
      and 6 Penicillium expansum strains isolated on board the Mir space station showed
      that all these strains synthesize metabolites of alkaloid origin (roquefortine,
      3,12-dihydroroquefortine, meleagrin, viridicatin, viridicatol, isorugulosuvin,
      rugulosuvin B, N-acetyl-tryptamine, and a "yellow metabolite" containing the
      benzoquinone chromophore).

PMID- 12526199
TI  - [The production of phenazine antibiotics by the Pseudomonas aureofaciens strain
      with plasmid-controlled resistance to cobalt and nickel].
AB  - Plasmid pBS501 responsible for the resistance of the wild-type Pseudomonas sp.
      BS501 (pBS501) to cobalt and nickel ions was conjugatively transferred to the
      rhizosphere Pseudomonas aureofaciens strain BS1393, which is able to synthesize
      phenazine antibiotics and to suppress a wide range of phytopathogenic
      microorganisms. The transconjugant P. aureofaciens BS1393 (pBS501) turned out to
      be resistant to cobalt and nickel with an MIC of 8 mM. When grown in a synthetic
      medium with 0.25 mM cobalt, the transconjugant accumulated 6 times more cobalt
      than the wild-type strain BS501 (pBS501) (1.2 and 0.2 microgram Co/mg protein).
      Electron microscopic studies showed that cobalt accumulates on the surface of
      transconjugant cells in the form of electron-opaque granules. In a culture medium
      with 2 mM cobalt or nickel, strain BS1393 produced phenazine-1-carboxylic acid in
      trace amounts. The transconjugant P. aureofaciens BS1393 (pBS501) produced this
      antibiotic in still smaller amounts. Unlike the parent strain BS1393, the
      transconjugant P. aureofaciens BS1393 (pBS501) was able to suppress in vitro the
      growth of the phytopathogenic fungus Gaeumannomyces graminis var. tritici 1818 in
      a medium containing 0.5 mM cobalt or nickel.

PMID- 12526200
TI  - [Magnesium orthophosphate, a new form of reserve phosphates in the halophilic
      archaeon Halobacterium salinarium].
AB  - The accumulation and utilization of reserve phosphates in the extremely
      halophilic archaeon Halobacterium salinarium were studied. The growth of H.
      salinarium was found to depend on the initial concentration of inorganic
      phosphate (Pi) in the culture medium and its content in the inoculum. Growing
      cells consumed 85-95% of Pi from the medium. Unlike the reserve phosphates of
      many other microorganisms, which are mainly polyphosphates, the reserve
      phosphates of H. salinarium cells contain no more than 15% polyphosphates, the
      rest being magnesium orthophosphate. The excessive consumption of Pi from the
      medium changed cell morphology and caused the death of part of the cell
      population. The cells that remained viable could grow in a Pi-deficient medium,
      utilizing about 70% of reserve magnesium phosphate as the phosphorus source.

PMID- 12526201
TI  - [Dormant cells in the developmental cycle of Blakeslea trispora: distinct
      patterns of the lipid and carbohydrate composition].
AB  - We revealed differences in the lipid and carbohydrate composition between cells
      of mucorous fungi during endogenous and exogenous dormancy. Endogenous dormancy
      (zygospores) is characterized by high contents of phosphatidylcholine (about 70%
      of total phospholipids) and triacylglycerol (over 90% of total neutral lipids).
      By contrast, exogenous dormancy (sporangiospores) is accompanied by elevated
      amounts of sterols, sterol esters, and free fatty acids, which account for over
      70% of total neutral lipids. We established for the first time significant
      differences in the phospholipid composition between sporangiospores obtained from
      stylosporangia and sporangioles. Based on the data obtained, we regard the
      retardation of life-sustaining activities as a biochemical adaptation based on
      the dormancy state. We also discuss the taxonomical position of B. trispora.

PMID- 12526202
TI  - [The biosynthesis of new secretory high-molecular-weight ribonucleases in
      Bacillus intermedius and Bacillus subtilis].
AB  - The investigation of new secretory ribonucleases, the Bacillus intermedius binase
      II expressed in the recombinant B. subtilis strain 3922 and the native RNase Bsn
      of B. subtilis, showed that they are synthesized in the growth retardation phase,
      when inorganic phosphate is exhausted in the medium. The biosynthesis of these
      ribonucleases was found to be suppressed by the presence of inorganic phosphate
      in the medium and activated by small amounts of the transcriptional inhibitor
      actinomycin D. The cultivation media of the producing strains were optimized for
      the maximum production of the enzymes.

PMID- 12526203
TI  - [Phenotypic features of Ferroplasma acidiphilum strains Yt and Y-2].
AB  - Earlier, we described a new family of mesophilic, strictly autotrophic Fe(2+)
      oxidizing archaebacteria, Ferroplasmaceae, which belongs to the order
      Thermoplasmales and includes the genus Ferroplasma and species F. acidiphilum
      (strain YT) [1]. The present work is concerned with a comparative study of
      phenotypic characteristics of the type strain YT and a new strain, F. acidiphilum
      Y-2, isolated from dense pulps produced during oxidation of arsenogold
      concentrates from the Bakyrchikskoe (Kazakhstan) and Olimpiadinskoe (Krasnoyarsk
      Krai) ore deposits, respectively. The G + C content of DNA from strains YT and Y
      2 comprised 35.1 and 35.2 mol%, respectively; the level of DNA-DNA homology
      between the strains was 84%. Restriction profiles of chromosomal DNA from both
      strains exhibited a similarity coefficient of 0.87. Genotypic characteristics of
      these strains indicate their affiliation to the same species. The cells of both
      strains are polymorphic and lack cell walls. Strains of F. acidiphilum oxidized
      ferrous oxide and pyrite as the sole source of energy and fixed carbon dioxide as
      the sole carbon source. Strains required yeast extract as a growth factor.
      Optimum pH for cell growth ranged from 1.7 to 1.8; the temperature optima for the
      growth of strains YT and Y-2 were 34-36 and 40-42 degrees C, respectively.
      Comparative analysis of total lipids revealed their close similarity in the
      strains; two glycophospholipids comprised 90% of total lipids: lipid I, beta-D
      glucopyranosylcaldarchaetidylglycerol (about 55%), and lipid II,
      trihexosylcaldarchaetidylglycerol (26%), whose isopranyl chains contained no
      cyclopentane rings. The carbohydrate fraction of lipid I hydrolysate contained
      only D-glucose, whereas hydrolysate of lipid II contained both D-glucose and D
      galactose in a molar ratio of 2:1. Thus, it was established that the
      intraspecific phylogenetic divergence within F. acidiphilum is manifested in two
      the strains by different temperature optima against the background of similarity
      in other phenotypic properties.

PMID- 12526204
TI  - [Comparison of genomes in Streptococcus thermophilus strains of different
      origins].
AB  - According to DNA hybridization data, thermophilic streptococci used in Russia as
      starters in the dairy industry are divided into 6 different genomovars, with a
      degree of DNA homology not exceeding 20-50%. The analysis of genomes from these
      genomovars using SmaI restriction endonuclease and pulsed-field gel
      electrophoresis revealed a wide variability of the genome size. In some strains,
      the genome size considerably exceeded 2000 kbp. Most of the strains studied
      contained plasmids about 120 kbp in size.

PMID- 12526205
TI  - [Characterization of thermophilic spore-forming bacteria from a geothermal spring
      in Lithuania based on 16S rDNA and 16S-23S rDNA intergenic spacers analyses].
AB  - Forty-two strains of gram-positive, aerobic, heterotrophic, obligately
      thermophilic, spore-forming bacteria were isolated from a geothermal site near
      the Baltic Sea in Lithuania. All of the strains were able to hydrolyze collagen
      and/or casein. Since characteristics of proteolytic activity are correlated with
      taxonomic positions of bacteria, the strains were grouped on the basis of
      molecular biological analyses. On the basis of RFLP patterns of 16S rDNA and 16S
      23S rDNA ITS-PCR analysis, the strains were subdivided into nine groups.

PMID- 12526206
TI  - [Cloning of the GSH1 and GSH2 genes complementing the defective biosynthesis of
      glutathione in the methylotrophic yeast Hansenula polymorpha].
AB  - The cloning of 7.2- and 9.6-kbp fragments of the methylotrophic yeast Hansenula
      polymorpha DNA restored the wild-type phenotype Gsh+ in the glutathione-dependent
      gsh1 and gsh2 mutants of this yeast defective in glutathione (GSH) synthesis
      because of a failure of the gamma-glutamylcysteine synthetase reaction. The 9.6
      kbp DNA fragment was found to contain a 4.3-kbp subfragment, which complemented
      the Gsh- phenotype of the gsh2 mutant. The Gsh+ transformants of the gsh1 and
      gsh2 mutants, which bear plasmids pG1 and pG24 with the 7.2- and 4.3-kbp DNA
      fragments, respectively, had a completely restored wild-type phenotype with the
      ability to synthesize GSH and to grow in GSH-deficient synthetic media on various
      carbon sources, including methanol, and with acquired tolerance to cadmium ions.
      In addition, the 4.3-kbp DNA fragment borne by plasmid pG24 eliminated
      pleiotropic changes in the gsh2 mutants associated with methylotrophic growth in
      a semisynthetic (GSH-supplemented) medium (poor growth and alterations in the
      activity of the GSH-catabolizing enzyme gamma-glutamyltransferase and the
      methanol-oxidizing enzyme alcohol oxidase).

PMID- 12526207
TI  - [Detection of microorganisms in the environment and the preliminary appraisal of
      their physiological state by X-ray microanalysis].
AB  - The paper deals with the X-ray microanalysis of the elemental composition of
      bacteriomorphic particles in 170,000-year old Antarctic permafrost sediments and
      in indoor dust. A comparative analysis of the phosphorus, sulfur, calcium, and
      potassium contents and the Ca/K and P/S ratios in these particles and in
      reference microbial cells occurring in different physiological states showed that
      the absence of P and/or S peaks in the X-ray spectrum of an object may indicate
      that it is abiotic. Resting microbial forms can be revealed on the basis of the
      following characteristic features: an increased content of Ca, a high Ca/K ratio,
      and a low P/S ratio. Model experiments with nonviable bacterial and yeast
      micromummies with alterations in the structural and barrier functions of the
      cytoplasmic membrane showed that micromummies can be recognized by a super-high
      content of a marker element (e.g., P, K, or Si), accumulated due to facilitated
      diffusion along the deliberately created concentration gradient. Such an analysis
      of the permafrost sediment and dust made it possible to suggest the presence of
      mummified cells in these objects. The possibility of using X-ray microanalysis
      for the detection of microbial cells in natural habitats in order to enhance the
      efficiency of ecological monitoring of the environment is discussed.

PMID- 12526208
TI  - [Dynamics of microbial processes in the stratal waters of the Romashkinskoe oil
      field].
AB  - Dynamics of the microbial processes developing in parallel with the exploitation
      of the Romashkinskoe oil field (Tatarstan) was studied in two areas differing in
      the degree of stratal water freshening. Flooding the strata in conjunction with
      purposeful measures on stratal microflora activation was shown to increase the
      microbial population density and activate both methanogenesis and sulfate
      reduction; the latter process was limited by the low sulfate concentration.
      Development of anaerobic processes correlated with changes in acetate
      concentration in the stratal water. High mineralization (over 200 g/l) inhibited
      the stratal water microflora even if other conditions were favorable. Isotopic
      analysis of the carbonate carbon showed that the bicarbonate concentration
      increased in the stratal water due to microbial degradation of oil hydrocarbons
      and further participation of the biogenic carbon dioxide in dissolution of the
      carbonate cement of the oil-bearing strata. In strongly desalinated stratal
      water, the proportion of the newly formed bicarbonate was as high as 80%.

PMID- 12526209
TI  - [Protective role of protons during hypoosmotic stress in the extremely halophilic
      archaeon Halobacterium salinarum].

PMID- 12526210
TI  - Analysis of bromodomain of BRD-7 gene and its prokaryotic expression.
AB  - BACKGROUND & OBJECTIVE: BRD-7 is a novel gene (AF: 152604), containing a
      bromodomain, was cloned in our lab. Previous studies showed that BRD-7 plays an
      obviously suppressive role on NPC cell growth. In order to clarify the function
      mechanism of this gene, we investigate an important motif of BRD-7, the
      bromodomain. METHODS: The bromodomain of BRD-7 was analyzed by homology-based
      amino sequence and secondary structure analysis. In addition, we constructed a
      prokaryotic expression vector of bromodomain. Western blot analysis was used to
      confirm the expression of the bromodomain protein in Escherichia coli. RESULTS:
      Homology-based sequence analysis revealed that the bromodomain of BRD-7 possibly
      contains four alpha helices (Z, A, B and C), and a hydrophobic pocket which is an
      important structure to recognize acetylated histone peptide. This bromodomain
      encoding a 12.8 kD protein, was introduced into Escherichia coli using the pGEX
      4T-2 expression vector. After isopropyl beta-D-thiogalactopyranoside(IPTG)
      induction, a new anticipated protein of 38.8 kD appeared on SDS-PAGE and the
      result was confirmed by Western blot analysis. CONCLUSION: BRD-7 of bromodomain
      protein is similar to three proteins containing known structural bromodomain
      motif by bio-informatics analysis, suggesting the bromodomain of BRD-7 should
      belong to co-activator subgroup and may have similar function that can
      selectively interact with acetylated histone peptide.

PMID- 12526211
TI  - [Effects of two haplotypes of HCAP1 gene on cellular gene expression levels in a
      human hepatocarcinoma cell line Hep3B].
AB  - BACKGROUND AND OBJECTIVE: HCAP1 gene is a novel gene cloned in our laboratory,
      which has two haplotypes(N and M). This study was designed to investigate the
      effects of two haplotypes of HCAP1 gene on cellular gene expression levels in a
      human hepatocarcinoma cell line Hep3B. METHODS: The Hep3B-Tet-on cells were
      transfected with HCAP1N or HCAP1M using liposome transfection reagent. In order
      to obtain the cells with high inducible expression of HCAP1N or HCAP1M, the
      transfected cells were screened by Western blot. Then, human atlas cDNA
      expression arrays were used to analyze the cellular gene expression profiles
      before and after HCAP1N or HCAP1M over-expression. The hybridization results were
      analyzed with FR-200 image system. RESULTS: The profiles of differential gene
      expression before and after HCAP1N or HCAP1M over-expression were established.
      These data indicated that over-expression of HCAP1M resulted in an up-regulation
      of genes involved in cellular proliferation (e.g., c-erbB2 receptor and
      transcription factor DP2) and a down-regulation of genes involved in cell
      apoptosis (caspase9) or DNA excision repair (ERCC5). While overexpression of
      HCAP1N resulted in an up-regulation of genes involved in cellular suppressors
      (e.g., snoN and WAF1) or DNA excision repair (ERCC5) and a down-regulation of
      genes involved in anti-apoptosis (HSPs). CONCLUSION: Over-expression of HCAP1M
      may promote cell proliferation. Over-expression of HCAP1N may suppress cell
      growth.

PMID- 12526212
TI  - [Effect of JIP on the proliferation and apoptosis of nasopharyngeal carcinoma
      cells].
AB  - BACKGROUND & OBJECTIVE: Previous studies showed that JNK signaling pathway
      activated by LMP1 plays an important role in carcinogenesis of nasopharyngeal
      carcinoma (NPC). JNK interacting protein (JIP) can inhibit JNK signaling pathway
      in NPC cell. This study was designed to elucidate the effect of JIP on the
      proliferation and apoptosis of NPC cells. METHODS: After treatment with JIP at
      different concentrations and time points, the number of proliferating cells were
      determined by MTT assay; the ability of proliferation of NPC cells was measured
      by the rate of cloning formation; cell cycle and the apoptotic rate of NPC cells
      was assayed by flow cytometry. RESULTS: 1. MTT assay showed that cell
      proliferation was significantly inhibited by JIP in a dose- and time-dependent
      manner. After treatment with JIP for 24, 48, and 72 hours, the rate of survival
      cells were 77.8%, 59.2%, and 61.8%, respectively. 2. The number and volume of
      colonies were decreased after transfection with JIP. 3. The number of cells in S
      phase was decreased from 25.87% to 19.96%, and the number of cells in G0/G1 phase
      was elevated from 66.24% to 71.89% after treatment with JIP. 4. In contrast to
      the control group, the 24 hours apoptotic rate was elevated from 1.25% to 8.25%
      (about 6.6 times); the 48 hours apoptotic rate was elevated from 1.04% to 31.45%
      (about 30 times). CONCLUSIONS: The results demonstrated that JIP inhibit the
      growth of nasopharyngeal carcinoma through arresting the cell cycle at G1/S
      checkpoint and triggering the apoptosis of cells. Data suggest that JIP is a
      potent molecular drug for the treatment of the patients with nasopharyngeal
      carcinoma.

PMID- 12526213
TI  - [Expression of PC-1 gene in tumor tissues, cloning and analysis of its putative
      promoter region].
AB  - BACKGROUND & OBJECTIVE: PC-1 is a novel gene which is overexpressed in bone
      metastasis and androgen independent prostate cancer cell line C4-2. The objective
      of this study was to evaluate the expression level of PC-1 gene in multiple human
      tumor and normal tissues, and clone a series of putative PC-1 gene promoter
      regions and analyze their promoter activities. METHODS: PC-1 gene specific DNA
      sequence was used as probe to hybridize with total RNA from 10 pairs of tumor and
      normal tissues; The C4-2 cell genomic DNA was used as a template in the
      polymerase chain reaction to amplify PC-1 upstream regions from the translation
      initiation codon. The PCR product was directly cloned into the luciferase
      reporter vector pGL3-basic. C4-2 cells were transiently transfected with above
      recombinant plasmids and the putative promoter activities were analyzed by
      luciferase assay. RESULTS: PC-1 gene expression level is remarkable higher in
      multiple tumor tissues than in their matched normal tissues; there is no promoter
      activity in the 340 bp fragment from the upstream of initiation codon, while 1099
      bp, 1337 bp, 1579 bp, 1831 bp, and 4939 bp fragments had the promoter activities.
      CONCLUSION: The PC-1 gene expression is specifically activated in multiple human
      tumor tissues, suggesting that PC-1 gene expression might be involved in cancer
      development. Our primary data shows that the highest promoter activity of PC-1
      gene is within the 4939 bp DNA fragment and maybe there exists an enhancer
      element between the 1831 bp and 4939 bp area.

PMID- 12526214
TI  - [Matrix metalloproteinases map of lymphogenous metastasis of hepatocarcinoma cell
      in mice].
AB  - BACKGROUND & OBJECTIVE: Metastasis is the leading cause of tumor-related death,
      in which lymphogenous metastasis is the most common pattern and also a bridgehead
      of further metastasis. However, the molecular mechanism of metastasis is
      uncertain. This study was designed to investigate the correlation between the
      metastasis of hepatocarcinoma cell(HCC) to lymphnode and matrix
      metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor
      cells in lymphnodes. METHODS: The maps of MMPs in supernatants of mouse HCCs with
      different metastatic potential Hca-F(high potential) and Hca-P cells(low
      potential) cultured with extract of lymph node, liver or spleen were examined by
      zymographic analysis. Growth fraction of lymphocytes in lymph nodes of tumor
      burden mice was detected by flow cytometry. The apoptosis signals of macrophages
      in lymph nodes were observed with TUNEL staining. The expressions of Fas ligand
      of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry.
      RESULTS: With the presence of the extraction of lymph note, the quantity of MMP-9
      significantly increased (P < 0.01): in RPMI1640 medium, the quantity of MMP-9
      produced by Hca-F and Hca-P were 1256 +/- 157 and 2642 +/- 385, respectively.
      After the addition of extraction of lymph node, the quantity of MMP-9 increased
      to 12,403 +/- 894 and 9086 +/- 686, respectively, together with the secretion of
      a large amount of MMP-2 (Hca-F: 7364 +/- 2001, Hca-P: 2997 +/- 1990) and active
      MMP-9 (Hca-F: 7297 +/- 1657, Hca-P: 3914 +/- 1253), and the amount of which was
      also more in Hca-F than in Hca-P cells(P < 0.05). There was no MMPs detected when
      the extraction of liver and spleen is present. The growth fraction of lymphocytes
      was as follow: in the Hca-F cells, the proliferating peak of lymphocytes appeared
      on the 14th day post-inoculation and then decreased rapidly, while in the Hca-P
      cells, the peak appeared on the 7th day post-inoculation and then kept at a high
      level. TUNEL staining showed that the positive signals of macrophages were
      detected around Hca-F cells. The expression of Fas ligand of Hca-F cells was
      stronger than that of Hca-P cells (P < 0.01). CONCLUSION: The MMPs secretion of
      Hca-F and Hca-P cell depend on the environment of lymph nodes. The increased
      expression of Fas ligand protein in Hca-F tumor cells with high lymphogenous
      metastatic potential in lymph nodes may help tumor cells escape from being killed
      by host lymphocytes.

PMID- 12526215
TI  - [Inhibitory effects of recombinant human endostatin on growth and metastasis of
      lung adenocarcinoma LA795 in mice].
AB  - BACKGROUND & OBJECTIVE: Generally, growth and metastasis of tumor are critically
      dependent on angiogenesis. Endostatin can specifically inhibits tumor
      angiogenesis. The current study was designed to evaluate the inhibitory effect of
      recombinant human endostatin (rhES) secreted by pichia, pastoris, GS115 on the
      growth and metastasis of mice lung adenocarcinoma LA795 in mice T739. METHODS: To
      select a strain that could highly express recombinant human endostatin, then
      induce the clone to express rhES by adding methanol. Purification of rhES was
      performed with heparin affinity chromatography. LA795 tumor cells were inoculated
      subcutaneously into the dorsa of T739 mice, and the mice were randomized into two
      groups. The first group was given rhES(20 mg/kg/d), and the second group was
      given equal volume of PBS, for 14 consecutive days. The volume of tumors were
      measured. And the tumor metastasis in the lungs of the mice was observed.
      RESULTS: The selected clone was induced to secrete enough soluble rhES. The
      purified protein could strongly inhibit growth and metastasis of mice lung
      adenocarcinoma LA795 in T739 mice (P < 0.001). CONCLUSION: The rhES secreted by
      pichia, pastoris, GS115 has good biological activities and greatly inhibit growth
      and metastasis of mice lung adenocarcinoma LA795 in mice T739.

PMID- 12526216
TI  - [Establishment and cytogenetic characterization of a human hepatocellular
      carcinoma cell strain from the embolus in portal vein].
AB  - BACKGROUND & OBJECTIVE: Poor prognosis of hepatocellular carcinoma (HCC) is due
      to its high recurrent rate after operation and early metastasis through portal
      vein. This study was designed to establish a metastatic HCC cell line and to
      investigate its molecular and cytogenetic characterization. METHODS: Cell culture
      was performed using the tissue obtained from a metastatic lesion in portal vein
      of a patient with HCC. After G-banding staining, karyotype, and comparative
      genomic hybridization (CGH) of the cultured H4M cells were characterized and
      cyclin D1 gene CCND1 was detected by differential PCR. RESULTS: The karyotype of
      metastatic HCC cell strain is a hypertriploid (71-78 chromosomes) with a huge
      marker chromosome containing a long homogeneously staining region (hsr). The main
      genetic alterations in H4M cells were a high copy number amplification of 11q13
      and loss of 8p. Cyclin D1 gene CCND1 was also amplified significantly in the
      cells. CONCLUSIONS: The loss of chromosome 8p and high copy number amplification
      of 11q13 are associated with the metastatic characteristics of H4M cells. The
      amplification of cyclin D1 gene CCND1 in H4M cells may be the cause of the
      amplification of chromosome 11q13.

PMID- 12526217
TI  - [Correlation and significance of E-cadherin and N-cadherin expression in prostate
      cancer].
AB  - BACKGROUND & OBJECTIVE: Decreased expression of E-Cadherin correlated with many
      kinds of cancer, but inappropriate expression of N-cadherin has been reported in
      breast cancer recently, which has a more distinct and direct role in promoting
      cancer cell motility than E-cadherin. The aim of this study was to investigate
      the correlation between E-Cadherin and N-Cadherin expression with the grade and
      stage of prostate cancer and their relationship with prostate specific antigen
      (PSA). METHODS: E-Cadherin and N-Cadherin expression in 56 prostate cancer
      samples were determined by immunohistochemical staining. RESULTS: Twenty-four
      patients (43%) were positive and 32 patients (57%) were negative in E-Cadherin
      expression. Eighteen patients (32%) were negative and 38 patients (68%) were
      positive in N-Cadherin expression. E-Cadherin and N-Cadherin were significantly
      related to the grade and stage of cancer and the change of F/T ratio (free
      prostate specific antigen/total prostate specific antigen ratio). There was no
      significant relationship between Cadherin expression and total prostate specific
      antigen (tPSA) or free prostate specific antigen (fPSA). CONCLUSION: E-Cadherin
      and N-Cadherin abnormal expressions may serve as the indicators to malignant
      degree and prognosis of the prostate cancer.

PMID- 12526218
TI  - [Expression of cyclooxygenase-2 in human transitional cell bladder carcinomas].
AB  - BACKGROUND & OBJECTIVES: Cyclooxygenase(COX) is a rate-limiting enzyme in
      prostaglandin synthesis. Recent study suggested that COX-2 was associated with
      carcinogenesis. This study was designed to investigate the role of COX in the
      development and progression of bladder cancer through examining the expression of
      COX-1 and COX-2 in human bladder cancer tissue, normal bladder mucosa, and
      cystitis tissue. METHODS: Reverse transcriptase-polymerase chain reaction(RT-PCR)
      and immunohistochemistry(Envision method) were applied to detect the mRNA and
      protein expression of COX-1 and COX-2 in bladder transitional cell
      carcinoma(BTCC), tissue adjacent to cancer, normal bladder mucosa, and chronic
      cystitis tissue. Furthermore, the relationship between COX expression level and
      cancer pathologic parameters was analyzed. RESULTS: Using RT-PCR, all 15 frozen
      specimens from bladder cancer were shown to express COX-2 mRNA, while only 1 of 5
      specimens from grossly normal mucosa adjacent to cancer expressed COX-2 mRNA,
      with significant difference. But COX-1 mRNA was expressed constitutionally in all
      of the fresh cancer tissue samples. The immunohistochemical result was analogous
      to RT-PCR result. COX-2 protein was mainly localized at cytoplasm of malignant
      cell (positive rate was 50%) but was not expressed in normal bladder mucosa (n =
      4) and chronic cystitis tissues (n = 5). In contrast, COX-1 protein was mainly
      localized at smooth muscle cell of normal tissue and cystitis tissue(positive
      rate was 100%) but was not expressed in cancer tissue. In 40 paraffin embedded
      specimens of BTCC, the intensity of COX-2 expression was associated with tumor
      grade and stage. The level of COX-2 expression was higher in grade III tumor,
      than in grade I, II tumors, and was higher in invasive tumor (T2-T4) than in
      superficial tumor(Ta-T1). CONCLUSIONS: The expression of COX-2 mRNA and protein
      was enhanced in human BTCC, and was associated with the malignant degree of the
      tumor, indicating that COX-2 may play a key role in the development and
      progression of BTCC.

PMID- 12526219
TI  - [Coexpression of vascular endothelial growth factor and its receptors in human
      tumor cell lines].
AB  - BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF) play an
      important role in tumor angiogenesis through a paracrine mechanism, but the
      importance of its autocrine has not been fully elucidated. This study was
      designed to explore the gene coexpression pattern of VEGF and its receptors (Flt
      1 and KDR) in variety of human malignant cell lines. METHODS: After isolation of
      RNA from thirty tumor cell lines and four endothelial cells, gene expressions of
      VEGF and its receptors were measured by semi-quantitative reverse transcriptase
      polymerase chain reaction using the transcriptional level of the house-keeping
      gene for internal calibration. RESULTS: VEGF transcript was detected in the
      majority of tumor cell lines (29/30) and in all endothelial cell lines at
      moderate or high level, while the expression of VEGF was low in human umbilical
      vein endothelial cell (HUVEC). Moreover, Flt-1 gene expression was found in 50%
      of hematopoietic malignancies (6/12), 28% of solid tumors (5/18), and endothelial
      cells (EA. hy926 and HUVEC). In contrast, the expression of KDR gene was found in
      2 (16.7%) hematopoietic cell lines and 6 (33.3%) solid tumor lines. In
      endothelial cells, KDR gene expression was detectable in HMEC-1 and HUVEC only.
      However, ECV304 cells express neither Flt-1 nor KDR gene. CONCLUSION:
      Overexpression of VEGF gene in all tumor cell lines provides a potential
      biological marker for malignancies and the coexpression of VEGF with its
      receptors suggesting an autocrine pathway exists in tumor cells.

PMID- 12526220
TI  - [Correlation of invasion, metastasis, and prognosis in low and middle rectal
      cancer].
AB  - BACKGROUND & OBJECTIVE: Several reports have showed that three histologic
      variables (venous invasion, regional lymph node status, and depth of primary
      tumor penetration) were associated with the prognosis of colorectal
      adenocarcinoma patients. Based on these variables, a new classification system
      has been recommended. This study was designed to evaluate prognostic significance
      and risk factors of neoplasm in low and middle rectal cancer. METHODS: Four
      hundreds and eighty-four consecutive patients with low and middle rectal cancer
      were treated by the abdominoperineal resection (APR) (356 patients) and the low
      anterior resection(LAR) (128 patients) between 1990 and 1996. To determine the
      independent prognostic variables, the variables were evaluated both univariately
      and multivariately from the perspectives of oncologic outcome. RESULTS: The 5
      year survival rate for all patients was 71.1% (344/484), 63.5% (226/356) for APR
      and 92.2% (118/128) for LAR/SSR, respectively (P < 0.01). The resulting
      multivariate analysis using Cox regression showed that the three tumor variables
      were significantly associated with the 5-year survival (P < 0.01), the
      independent prognostic variables included venous invasion, tumor size, and TNM
      stages. CONCLUSIONS: The three tumor variables identified in multivariate
      analysis as bearing the strongest independent effect on the 5-year survival in
      low and middle rectal cancer were (in order to decrease prognostic impact) venous
      invasion, tumor size, and TNM stages. These three tumor variables may be used as
      important bases for a new classification system.

PMID- 12526221
TI  - [Expression and clinical significance of IGF-II mRNA and bcl-2 protein in
      colorectal adenocarcinomas].
AB  - BACKGROUND & OBJECTIVE: Insulin-like growth factor II (IGF-II) can stimulate cell
      proliferation; B cell lymphoma 2 (bcl-2) protein can strongly inhabit cell
      apoptosis. Recently, the overexpression of IGF-II and bcl-2 in colorectal cancer
      has been found, but the combined detection of them has not been reported. The
      objective of this study was to investigate the relationship between the
      expression of IGF-II, bcl-2 and the invasion, metastases of colorectal
      adenocarcinomas and to analyze the clinical significance of combined detection of
      these factors. METHODS: Forty-eight paraffin embedded samples from colorectal
      adenocarcinomas were selected. IGF-II mRNA was detected by using in situ
      hybridization. The expression of bcl-2 and PCNA protein were determined
      immunohistochemically, and TUNEL technique was used to detect apoptosis. Ten
      normal colorectal tissues were used as controls. The positive cell ratio of
      cancers was calculated by computer. The specimens with positive cell ratio < or =
      30% were defined as negative. RESULTS: The expressions of IGF-II mRNA and bcl-2
      protein were significantly higher in colorectal adenocarcinomas (38.70% +/- 7.80%
      and 30.97% +/- 7.40%) than in normal colorectal tissues(23.12% +/- 4.07% and
      12.69% +/- 1.31%) (P < 0.01) and were related to Dukes' stage and lymph node
      metastases but were not associated with patient's age, gender, tumor site, tumor
      size and tumor differentiation. A negative correlation was observed between IGF
      II mRNA and bcl-2 protein (P < 0.05). A positive correlation between IGF-II mRNA
      and PCNA, apoptosis as well as a negative correlation between bcl-2 and apoptosis
      were observed (P < 0.01). There was no correlation between bcl-2 and PCNA (P >
      0.05). The patients with IGF-II mRNA (+) and bcl-2 (-) were regarded as the worst
      prognosis. CONCLUSION: The overexpression of IGF-II and bcl-2 in colorectal
      adenocarcinomas play an important role in the pathogenesis, progression,
      invasion, and metastases of the tumor. Determination of both IGF-II and bcl-2
      expression would be helpful for decision making of adjuvant therapy.

PMID- 12526222
TI  - [Expression of mucin MUC1 and MUC2 in colorectal carcinoma and their clinical
      significance].
AB  - BACKGROUND & OBJECTIVE: The up-regulation of mucin MUC1 expression or down
      regulation of mucin MUC2 expression may be involved in carcinogenesis of some
      neoplasms, but there was few report about the relationship between mucin MUC1 and
      MUC2 expression and Chinese colorectal carcinoma. The aim of this study was to
      explore relationship between expression of mucin MUC1 and MUC2 in colorectal
      carcinoma and clinicopathological parameters and their clinical significance.
      METHODS: The expression of mucin MUC1 and MUC2 in 126 cases of colorectal
      carcinoma were detected by S-P immunohistochemical technique. RESULTS: The
      positive expression rates of mucin MUC1 and MUC2 in normal colorectal mucosa were
      0 and 100%, respectively, but the positive expression rates of mucin MUC1 and
      MUC2 in 126 cases of colorectal carcinoma were 42.1% and 36.5%, respectively (P <
      0.01); the expression of mucin MUC1 was positive correlated to the depth of
      invasion, lymph node metastasis, and Dukes staging (P < 0.05), but negative
      correlated to the degree of differentiation (P < 0.05); mucin MUC2 expression was
      related to invasion, lymph node metastasis, and Dukes staging (P < 0.05), but
      unrelated to differentiation (P > 0.05). CONCLUSIONS: The up-regulation of mucin
      MUC1 expression or down-regulation of mucin MUC2 expression may be involved in
      carcinogenesis and progression in colorectal carcinoma, and the detecting of
      mucin MUC1 and MUC2 may be predicting its prognosis in colorectal carcinoma.

PMID- 12526223
TI  - [Significance of MOC-31 and CD56 detection in human lung carcinoma tissues].
AB  - BACKGROUND & OBJECTIVE: The majority of research found that the positive rate of
      MOC-31 is higher in lung carcinoma than that in pleural mesothelioma. So MOC-31
      is regarded as an important factor in differentiating diagnosis of lung carcinoma
      from pleural mesothelioma. But there are also few contrary reports. CD56 (neural
      cell adhesion molecule) is a sensitive factor in diagnosis of small cell lung
      carcinoma (SCLC), but the reports about its diagnostic sensitivity in non-small
      cell lung carcinoma (NSCLC) are different. This study was conducted to
      investigate the significance of MOC-31 and CD56 in diagnosis of human lung
      carcinoma. METHOD: Immunohistochemical method (S-P) was used to detect MOC-31 and
      CD56 expression in 92 cases of lung carcinoma. RESULT: The positive rate of MOC
      31 in lung carcinoma was 98.9% (91/92), among which, 98.6% (72/73) in NSCLC, 100%
      (19/19) in SCLC; the positive expression rate of CD56 in lung carcinoma was 30.4%
      (28/92), among which, 12.3% (9/73) in NSCLC, 100% (19/19) in SCLC. MOC-31 and
      CD56 expressions in adjacent lung tissue and normal lung tissue were negative.
      CONCLUSION: MOC-31 is an antibody which is highly sensitive and peculiar to lung
      carcinoma, whereas CD56 only showed sensitive to SCLC. Therefore, combined
      determination of MOC-31 and CD56 is more useful than that of single item in
      diagnosing SCLC.

PMID- 12526224
TI  - [Analysis of clinical efficiency of treatment for 179 geriatric women with stage
      I or II cervical carcinoma].
AB  - BACKGROUND & OBJECTIVE: Elderly women with cervical carcinoma have the features
      of poor prognosis and high incidence rate of complications. This study was
      designed to evaluate the prognostic impact of surgery versus radiotherapy in old
      women with stage I and stage II cervical carcinoma and seek suitable treatment
      for such patients. METHODS: Clinical data of 179 elderly women with stage Ia to
      stage IIb cervical cancer were analyzed retrospectively. One hundred and thirty
      four cases underwent radical hysterectomy also received appropriate adjuvant
      radiotherapy and/or chemotherapy. Forty-five cases underwent radiation therapy
      received appropriate adjuvant chemotherapy. RESULTS: The 5-year survival rates of
      patients underwent surgery and radiotherapy were 78.32% and 49.08% (P = 0.04),
      respectively. The incidence rate of complications of patients receiving surgery
      was 47.01% (63/134). Three patients died of complications after radical
      hysterectomy. The incidence rate of complications of patients underwent
      radiotherapy was 75.63% (34/45). CONCLUSION: Geriatric patients with stage I and
      stage II cervical carcinoma should receive operation if possible and should
      receive adjuvant treatments according to personal conditions.

PMID- 12526225
TI  - [Significance of telomerase expression in diagnosis and treatment of breast
      tumor].
AB  - BACKGROUND AND OBJECTIVE: It was reported that the activation of telomerase can
      turn normal cell into tumor cell. This study was designed to investigate the
      expression of telomerase in breast tumor and its value for early diagnosis and
      treatment. METHODS: Telomerase expression in 178 breast tumor specimens was
      detected by using PCR-ELISA immunohistochemical method. RESULTS: Positive
      expression rate of telomerase in primary breast carcinoma, precancerous lesion of
      breast, breast fiber tumor were 86.72% (111/128), 46.67% (7/15), and 26.66%
      (4/15), respectively. Negative expression of telomerase was shown in normal
      breast tissue and cystic hyperplasia tissue. Positive expression rate of
      telomerase in different clinical stage were 63.16% in stage I, 85.96% in stage
      II, 95.65% in stage III, 100% in stage IV, respectively. Positive expression rate
      of telomerase in the patients with and without positive axillary lymph node were
      95.83% (69/72) and 75(42/56), respectively. CONCLUSION: Expression of telomerase
      was closely associated with clinical stages of breast cancer (P < 0.005) and
      metastases of axillary lymph node (P < 0.01). Special importance is that its
      expression was found in breast precancerous lesion, indicating its is
      significance in early diagnosis of breast cancer.

PMID- 12526226
TI  - [Expression and significance of p53 and proliferating cell nuclear antigen in
      malignant tumor of maxillary sinus].
AB  - BACKGROUND & OBJECTIVE: p53 and proliferating cell nuclear antigen (PCNA) play an
      important role in the development of malignant tumor. This study was designed to
      evaluate the role of p53 and PCNA in the development of malignant tumor of
      maxillary sinus by detecting their expression in malignant, benign, and
      inflammatory lesions of maxillary sinus. METHODS: The expressions of p53 and PCNA
      were detected by immunohistochemistry in 108 malignant, 19 benign, and 8
      inflammatory tissues of maxillary sinus. Rank sum test was used and the levels of
      positive degree of p53 and PCNA were represented by mean rank. RESULTS: The mean
      ranks of p53 and PCNA were 42.8 and 47.9 in inflammatory group and 50.3 and 46.8
      in benign group, but 73.0 and 73.2 in malignant group, respectively. In malignant
      group, mean rank of p53 in squamous cell carcinoma (SCC) was 60.7, which was
      higher than that in adenocarcinoma (43.9). The differences were significant (P <
      0.05). While from stage I to stage IV, the mean ranks of p53 were 46.6, 50.1,
      56.1, and 55.0 and the mean ranks of PCNA were 60.5, 48.8, 56.1, and.

PMID- 12526227
TI  - [Serum levels of VEGF and nitric oxide in esophageal squamous carcinoma patients
      and the clinical significance].
AB  - BACKGROUND & OBJECTIVE: Angiogenesis is necessary for the growth and metastasis
      of malignant tumor and is closely related to vascular endothelial growth factor
      (VEGF) and nitric oxide (NO). This investigation was aimed to detect the serum
      levels of VEGF and NO in squamous carcinoma patients and analyze the clinical
      significance for prognosis evaluation. METHODS: Serum VEGF and NO levels were
      detected by enzyme-linked immunosorbant assay (ELISA) and spectrophotometry,
      respectively, and their clinical significance was analyzed. RESULTS: Serum levels
      of VEGF and NO in squamous carcinoma patients were significantly higher than that
      of in normal persons (P < 0.01). There was a positive correlation between serum
      VEGF, NO levels and tumor pathological phases, histological grades and lymph node
      metastasis (P < 0.01). There was also a positive correlation between serum VEGF
      level and serum NO level (P < 0.01). CONCLUSION: Serum levels of VEGF and NO in
      squamous carcinoma patients were significantly correlated to the growth,
      development and malignant behavior of tumor and thus may serve as the indexes for
      clinical prognosis evaluation.

PMID- 12526229
TI  - [Analysis of 8 years follow up information of malignant tumor in industrial
      system of Guangzhou].
AB  - BACKGROUND & OBJECTIVE: Guangzhou is one of the advanced industry cities in
      China. To investigate the mortality of malignant tumor in workers from different
      industries can identify the high risk people who suffer from malignant tumor and
      have important significance to identify the relation between occupational factors
      and malignant tumor. This study was designed to follow up the dead situation of
      malignant tumor in workers from different industries in Guangzhou, and provide
      the data for prevention and treatment of tumors. METHODS: A total of 79,573
      workers, who exceed 35 years old, from 399 factories of Guangzhou were included
      in the prospective study for 8 years. It based on individual health files of 399
      factories from 1989 to 1992. The total mortality, mortality of malignant tumor,
      and the disease classification of malignant tumor were investigated by
      epidemiology and statistics. RESULTS: A total of 633,869 people year (393,373
      men, 30,195 women) have been trailed. The trailed time was more than 8 years. Of
      1577 dead employees, 801 died of malignant tumor (50.7%). Of all the occupational
      types of work, the mortality of malignant tumor in metallurgical industry is
      apparently higher than that in other industries. In rubber industry, the relative
      risk of malignant tumor mortality in old age group is higher than that in middle
      age group. The top three malignant tumors of death were digestive system,
      respiratory system and rhinopharynx malignant tumors. While the top three
      mortalities for single organ malignant tumor were lung cancer, liver cancer, and
      rhinopharynx cancer. CONCLUSIONS: At present, malignant tumor is a disease which
      severely imperil the life of workers in different industries of Guangzhou. It is
      important to do health check periodically in old age group.

PMID- 12526228
TI  - [Detection of serum tumor supplied group of factors and its clinical
      significance].
AB  - BACKGROUND & OBJECTIVE: Tumor supplied group of factors (TSGF) is the first kind
      of tumor marker in vitro which was primarily obtained the approval by Chinese
      government to land the market, there was no any reports about it in abroad
      before. In order to know its specificity and sensitivity, we designed this study
      to detect the TSGF in serum of the patients with malignancies and evaluate its
      clinical significance for diagnosis. METHODS: Serum TSGF in 523 cases with
      malignancies and 400 cases of normal control were detected with chemical
      colorimetry. The diagnostic accuracy was evaluated. RESULTS: Mean levels of serum
      TSGF in the patients without malignancies (group A), the patients with
      malignancies (group B), the patients after curative treatment for malignancies
      (group C) and the normal control (group D) were 66.57, 71.24, 60.78, and 53.56
      u/ml, respectively. After the statistical analysis, differences between the group
      A and group B, group A and group D, group B and group C, group B and group D,
      group C and group D were found (P < 0.05). But there was no obvious difference
      between the group A and group C (P > 0.05). The sensitivity was 63.86%; the
      specificity was 90.89%; the truly negative rate was 87.01%; and the falsely
      negative rate was 13.00%. CONCLUSIONS: Serum TSGF increased in malignancies and
      may be helpful for screening and early detection of cancer.

PMID- 12526230
TI  - [The roles of DNA methylation in human neoplasms].
AB  - Recent data suggested that cancer appears to be a process that is fuelled both by
      genetic alterations and by epigenetic mechanisms. Epigenetics refer to the study
      of changes in gene expression that can be mitotically inherited, but is not
      associated with the changes in the coding sequence of the affected genes. DNA
      methylation, the best understood mechanism in epigenetics, is an enzyme-mediated
      chemical modification that adds methyl (CH3) groups at selected sites on DNA. In
      humans and most mammals, DNA methylation only affects the cytosine base (C), when
      it is followed by a guanosine (G). DNA methylation in the promoter regions is a
      powerful mechanism for the suppression of gene activity. It was thought formerly
      that two pathways by which tumor suppressor genes became disabled were intragenic
      mutations and loss of chromosomal material [(loss of heterozygosity (LOH) or
      homozygous deletion)]. More recent studies have firmly established methylation as
      one potential hit and represent a third mechanism by which tumor suppressor genes
      are inactivated, and that, in some cases, methylation is the sole mechanism
      responsible for the inactivation of a tumor suppressor gene. There is clearly a
      tumor-specific methylation pattern in many types of tumor. An individual tumor
      within a single patient may have characteristic set of gene with an increased
      propensity to become methylated as compared with a tumor of the same type in a
      different patient. Methylation changes appear to precede apparent malignancy in
      many cases. Therefore, methylation can distinguish tumor types and subtypes, and
      should be useful in improving early detection of potentially cancerous cells.
      Methylation markers may also be used to predict response to chemotherapy or
      duration of patient survival. The efficacy of hypomethylating agents (e.g. 5-aza
      2'-deoxycytidine) as antineoplastic agents has been attributed to two distinct
      mechanism: cytotoxicity and induction of hypomethylation. Some clinical trials
      with them have been performed in solid tumors and malignant hematologic disease.
      In general, the response rates were not satisfactory. A variety of methods are
      used to evaluate the methylation status of genes. MSP (methylation-specific PCR)
      is very sensitive and has been widely used. It takes advantage of the DNA
      sequence difference existing between methylated and unmethylated DNA after
      bisulfite treatment.

PMID- 12526231
TI  - Dying by irreconcilable numbers.

PMID- 12526232
TI  - Factors to consider when analyzing 12-lead electrocardiograms for evidence of
      acute myocardial ischemia.
AB  - An important factor to consider when using findings on electrocardiograms for
      clinical decision making is that the waveforms are influenced by normal
      physiological and technical factors as well as by pathophysiological factors.
      Traditionally, the focus of bedside monitoring is detection of arrhythmia.
      However, continuous ST-segment monitoring for the detection of myocardial
      ischemia is now readily available. Many factors affect electrocardiographic
      waveforms and may interfere with diagnosis of myocardial ischemia based on
      electrocardiographic findings. Accordingly, a principal leadership role for
      clinical nurse specialists and nurse practitioners is to become knowledgeable
      about interpretation of 12-lead electrocardiograms and to share this knowledge
      with staff nurses who care for patients with acute coronary syndromes. The
      factors that alter electrocardiographic findings are reviewed, and the
      alterations that interfere with electrocardiogram-based diagnosis of myocardial
      ischemia are discussed.

PMID- 12526233
TI  - Critical care nurses' beliefs about and reported management of anxiety.
AB  - BACKGROUND: Anxiety is associated with increased morbidity and mortality.
      Critical care nurses are uniquely positioned to reduce anxiety in their patients.
      Critical care nurses' beliefs about and frequency of use of strategies to reduce
      anxiety have not been studied. OBJECTIVES: To explore critical care nurses'
      beliefs about the importance of anxiety management and to describe nurses'
      reported use of strategies to manage anxiety in their patients. METHODS: A random
      sample (N = 2500) of members of the American Association of Critical-Care Nurses
      was asked to complete the Critical Care Nurse Anxiety Identification and
      Management Survey. RESULTS: Respondents (n = 783) were primarily female (92%),
      white (88.5%) staff nurses (74.1%) who thought that anxiety is potentially
      harmful (mean, 4.1; SD, 0.8; range, 1 = no harm to 5 = life-threatening harm),
      that anxiety management is important (mean, 4.8; SD, 0.6; range, 1 = not
      important to 5 = very important), and that effective anxiety management is
      beneficial (mean, 4.6; SD, 0.6; range, 1 = no benefit to 5 = profound benefit). A
      majority commonly used pharmacological management; most also used information and
      communication interventions. Fewer subjects used the presence of patients' family
      members to alleviate patients' anxiety; few reported using stress-reduction
      techniques. CONCLUSION: Most respondents thought that treating anxiety is
      important and beneficial. Commonly used strategies included pharmacological
      relief of anxiety and pain and information and communication interventions.
      Although these strategies are useful, they may not effectively reduce anxiety in
      all patients.

PMID- 12526234
TI  - Use of heliox to avoid intubation in a child with acute severe asthma and
      hypercapnia.

PMID- 12526236
TI  - Comparing basic knowledge in critical care nursing between nurses from the United
      States and nurses from other countries.
AB  - BACKGROUND: No previous research was found that compared basic knowledge in
      critical care nursing among nurses from different nations. Nurses from outside
      the United States were invited to participate during reliability testing of the
      Basic Knowledge Assessment Tool, Version 5. PURPOSE: To compare basic knowledge
      in critical care between nurses from the United States and nurses from other
      countries and to measure the reliability of the Basic Knowledge Assessment Tool,
      Version 5. SAMPLE: Data were collected for 16 months from 682 critical care
      nurses: 528 from the United States and 154 from other countries. RESULTS: The
      Basic Knowledge Assessment Tool, Version 5, was a reliable test for all nurses
      studied, regardless of country of origin. The level of knowledge of nurses from
      English-speaking countries other than the United States did not differ from that
      of nurses from the United States. Scores for nurses from non-English-speaking
      nations were lower than scores for nurses from the United States. The largest
      source of variance in scores among all subjects was the length of experience in
      critical care nursing. CONCLUSIONS: The Basic Knowledge Assessment Tool, Version
      5, is a valid and reliable tool for assessing critical care nurses from the
      United States and the other countries studied. Critical care nurses from English
      speaking countries scored higher than nurses from countries where the primary
      language is not English.

PMID- 12526235
TI  - Effect of tracheal gas insufflation during weaning from prolonged mechanical
      ventilation: a preliminary study.
AB  - BACKGROUND: Tracheal gas insufflation reduces inspired tidal volume and minute
      ventilation in spontaneously breathing patients and may facilitate weaning from
      mechanical ventilation. OBJECTIVE: To determine if tracheal gas insufflation can
      reduce ventilatory demand during weaning trials in patients who require prolonged
      mechanical ventilation. METHODS: A reduction in ventilatory demand was defined as
      a relative decrease in tidal volume, minute ventilation, and mean inspiratory
      flow during trials with tracheal gas insufflation compared with the values during
      trials without this therapy. A total of 14 subjects underwent T-piece trials with
      and without insufflation (flow rate 6 L/min) on 2 consecutive days; the order of
      insufflation was randomized. Tidal volume, minute ventilation, and mean
      inspiratory flow were measured at baseline (without insufflation) and 2 hours
      later. RESULTS: Differences in ventilatory demand were not significant when
      comparisons were made for condition (tracheal gas insufflation vs no flow) or
      time (baseline vs 2 hours) for the total group (P = .48). Subjects were
      classified post hoc as responders (n = 9) or nonresponders (n = 5). Comparisons
      between responders and nonresponders indicated a significant (P = .02) 3-way
      multivariate interaction for group (responder vs nonresponder), condition
      (tracheal gas insufflation vs no flow), and time (baseline vs 2 hours) for
      ventilatory demand variables. CONCLUSION: Tracheal gas insufflation can reduce
      ventilatory demand during weaning trials in some patients who require mechanical
      ventilation.

PMID- 12526237
TI  - Cardiorespiratory nurses' perceptions of palliative care in nonmalignant disease:
      data for the development of clinical practice.
AB  - Nurses lack a comprehensive body of scientific knowledge to guide the palliative
      care of patients with nonmalignant conditions. Current knowledge and practice
      reveal that nurses in many instances are not well prepared to deal with death and
      dying. Focus groups were used in an exploratory study to examine the perceptions
      of palliative care among cardiorespiratory nurses (n = 35). Content analysis was
      used to reveal themes in the data. Four major themes were found: (1) searching
      for structure and meaning in the dying experience of patients with chronic
      disease, (2) lack of a treatment plan and a lack of planning and negotiation, (3)
      discomfort in dealing with death and dying, and (4) lack of awareness of
      palliative care philosophies and resources. The information derived from this
      sample of cardiorespiratory nurses represents a complex interplay between
      personal, professional, and organizational perspectives on the role of palliative
      care in cardiorespiratory disease. The results of the study suggest a need for
      nurses to be equipped on both an intellectual and a practical level about the
      concept of palliative care in nonmalignant disease.

PMID- 12526238
TI  - Heart period variability of intubated very-low-birth-weight infants during
      incubator care and maternal holding.
AB  - BACKGROUND: Heart rate has been used to measure infants' physiological stability
      during skin-to-skin holding. Variability in heart period (interbeat interval), a
      more sensitive measure of autonomic nervous system tone, has not. OBJECTIVE: To
      describe heart period variability in intubated very-low-birth-weight infants
      during incubator care and during maternal skin-to-skin holding. DESIGN/METHODS:
      An experimental, interrupted time series, crossover design was used; infants
      served as their own controls. Infants were randomly assigned to treatment order:
      2 hours of intermittent skin-to-skin holding for 2 consecutive days followed by 2
      days of incubator care or vice versa. The analog signal representing heart period
      was sampled and quantized at 5 Hz via a dedicated computer system in multiple 300
      second epochs each day. RESULTS: Fourteen infants with similar characteristics
      completed the protocol. The mean interbeat interval was 332 ms during skin-to
      skin care and 368 ms during incubator care. Power within the low- and high
      frequency regions of heart period was not significantly different between skin-to
      skin holding and incubator care. Mean low-frequency power was 124.6 ms2 during
      skin-to-skin holding and ranged from 51.9 ms2 to 71.4 ms2 during all periods of
      incubator care. Mean high-frequency power was similar during skin-to-skin holding
      and incubator care (8.8 ms2 and 6.1 ms2). Infants of 32 to 34 weeks' corrected
      gestational age had increased power in the low- and high-frequency regions.
      CONCLUSIONS: Heart period variability did not improve during skin-to-skin
      holding. Gestationally older infants had increased power in the low- and high
      frequency regions, suggesting a maturing autonomic nervous system.

PMID- 12526239
TI  - Perceived self-efficacy in performing and willingness to learn cardiopulmonary
      resuscitation in an elderly population in a suburban community.
AB  - BACKGROUND: Older persons are the group most likely to respond to cardiac arrests
      in private residences. OBJECTIVE: To characterize the knowledge about, attitudes
      toward, and perceived self-efficacy of older persons in learning and providing
      cardiopulmonary resuscitation. METHODS: A total of 2743 surveys were mailed to
      adults 55 years and older who resided in a single Michigan suburb. Data were
      collected on demographics, medical history, training in and willingness to
      provide cardiopulmonary resuscitation, and concerns about providing this
      intervention. RESULTS: The 631 persons (24.6%) who responded were elderly (mean
      age, 73.5 years) and had a mean of 1.7 occupants per household. More than one
      third lived alone. Of all respondents, 275 (43.6%) had received training in
      cardiopulmonary resuscitation, 370 (58.6%) indicated a willingness to learn
      cardiopulmonary resuscitation, and 412 (65.3%) thought that they had the ability
      to perform this intervention. Respondents 80 years or younger were significantly
      more likely than respondents more than 80 years old to be willing to learn
      cardiopulmonary resuscitation (65.7% vs 19.0%, P < .001) and perceived themselves
      as able to perform it (73.0% vs 34.0%, P < .001). The absence of mouth-to-mouth
      ventilation as part of training had minimal impact on the willingness of either
      age group to receive training (61.2% vs 58.6%, P = .19). Perceived ability to
      learn and perform cardiopulmonary resuscitation did not vary with the medical
      history of the respondent or the respondent's spouse. CONCLUSION: Adults 56 to 80
      years old perceive themselves as able to perform cardiopulmonary resuscitation
      and are interested in receiving training.

PMID- 12526240
TI  - Avoiding ethical emergencies.

PMID- 12526241
TI  - Seminal changes in the management of the acute coronary event: current concepts.
AB  - In the past era, we held high-grade arterial stenosis responsible for the acute
      complications of atherosclerosis. These concepts are being reassessed.
      Qualitative rather than quantitative aspects of plaques (e.g., inflammation
      rather than plaque size) have been established as decisive determinants of their
      probabilities to cause acute complications. Numerous beneficial effects of
      statins have been demonstrated. These include lipid lowering, plaque stability,
      enhanced endothelial function, and antiplatelet, antiatherothrombotic, and
      antimacrophage activities. However, the successful medical management of CAD is
      also multifactorial and in addition to use of statins include beta-blockers, ACE
      inhibitors, and aspirin, as well as blood pressure control, diet, and exercise
      (see [figure: see text] Figure). The results have been not only the preventions
      of acute complications of atherosclerosis, but also the successes in stabilizing
      acute coronary events and preventing infarctions.

PMID- 12526242
TI  - Heart blocks.

PMID- 12526243
TI  - Clinical factors influencing the eosinophil infiltration of nasal polyps.
AB  - AIMS AND METHODS: Our study, based on a retrospective chart analysis, was aimed
      1) to describe the varying degree of eosinophil infiltration in a series of 263
      adult patients operated on diffuse and bilateral nasal polyposis (NPS) after
      failure of medical treatment, in 15 cystic fibrosis patients with bilateral nasal
      polyps, and in 31 patients with chronic sinusitis without polyps (18 bilateral,
      13 unilateral) 2) to search for clinical factors that might influence the degree
      of eosinophil infiltration. Eosinophil infiltration was expressed semi
      quantativity as a percentage of inflammatory cells. RESULTS: Our study confirms
      that eosinophil infiltration is a striking feature of nasal polyposis. All
      patients with chronic sinusitis showed less than 10% eosinophils (mean +/- SEM =
      2 +/- 2%) whereas 88% of patients with NPS showed more than 10% eosinophils (50
      +/- 2%). Cystic fibrosis lied in between with 40% of patients showing more than
      10% eosinophils. In idiopathic bilateral NPS the number of eosinophils was
      increased in patients with asthma (58 +/- 3%) and even more in Widal's triad (75
      +/- 4%). Atopic patients did not have more eosinophils (52 +/- 5%). Patients
      treated with systemic steroids within two months before surgery showed decreased
      eosinophil infiltration (22 +/- 3% vs 50 +/- 2 for treated versus untreated)
      whereas patients treated with topical steroids did not (47 +/- 2%). CONCLUSIONS:
      Thus, a link might exist between clinical presentation and eosinophil
      infiltration. Chronic sinusitis and nasal polyps are probably not the same
      disease. Eosinophils appear as a link between nasal polyps, asthma and aspirin
      intolerance. Atopic status does not modify eosinophil infiltration of nasal
      polyps. Systemic steroids appear significantly more effective to reduce the
      eosinophil infiltrate than topical steroids in our selected group of operated
      patients.

PMID- 12526244
TI  - Computer-aided image-guided endoscopic sinus surgery in unusual cases of sphenoid
      disease.
AB  - The vital neurovascular structures that border the sphenoid sinus make extensive
      sphenoid sinus surgery hazardous despite the advent of endoscopic sinus surgery
      (ESS). Computer-aided image-guided endoscopic sinus surgery (CAIGESS) has
      facilitated safer surgery by providing real-time analysis of complex, three
      dimensional anatomic landmarks. We present 6 cases of atypical sphenoid disease,
      which greatly benefited from the unique superiority of CAIGESS in avoding
      surgical complications. Two cases of cerebrospinal-fluid (CSF) leak with
      concomitant meningoencephalocele of the sphenoid sinus were successfully managed
      with this technique. An inverting papilloma originating from the sphenoid sinus
      was successfully exenterated using CAIGESS. One patient, who experienced a
      lateral-rectus muscle palsy from sphenoid sinusitis, underwent successful
      sinusotomy with CAIGESS. Another patient, who had refractory left-sided sphenoid
      sinusitis despite 2 ESS procedures, was found to have an obliquely oriented
      intersinus septum which misled the previous surgeons to enter mistakenly the
      contralateral sphenoid sinus. CAIGESS allowed accurate identification and removal
      of the intersinus septum and relief of the sinusitis. Finally, a sphenoid-sinus
      mucocele that developed after a prior pituitary surgery was safely decompressed
      with CAIGESS. This surgical approach offers a new and effective adjunct to ESS in
      selected revision or difficult sinus cases and has proven invaluable in
      complicated sphenoid cases where the surrounding neurovascular anatomy could
      otherwise be jeopardized.

PMID- 12526245
TI  - The use of fibrin glue as hemostatic in endonasal operations: a prospective,
      randomized study.
AB  - Operations like septoplasty, rhinoplasty, nasal septal reconstruction and
      conchotomy may produce bleeding and postoperative hematoma. Two hundred four
      patients undergoing septoplasty and conchotomy operations were entered into a
      prospective study. Patients were randomly assigned to one of three treatment
      groups: Group I, septoplasty + conchotomy + nasal packing; Group II, septoplasty
      + conchotomy + fibrin glue; Group III, septoplasty + conchotomy + fibrin glue +
      transseptal suturing. To stop bleeding, we used the second generation surgical
      fibrin sealant Quixil and compared it with nasal packing. To increase protection
      against possible intraseptal hematoma we tried transseptal suturing at the end of
      a standard septoplasty operation. Our results show that the usage of the Quixil
      fibrin glue by aerosol spraying in endonasal operations is more effective and
      convenient than the usage of nasal packing. This combination of fibrin glue and
      the transseptal suturing substitutes the role of nasal packing in preventing
      postoperative intranasal hematoma. However, the transseptal suturing combined
      with the glue is not justified for the patients as no statistical difference was
      observed between Groups II and III in terms of occurrence of postoperative
      complications.

PMID- 12526246
TI  - Healing results of prolonged acute frontal sinusitis treated with endoscopic
      sinus surgery.
AB  - In a marked part of patients suffering from acute frontal sinusitis, the symptoms
      do not resolve after initial therapy (antibiotics and/or trephination). The
      prolongation of the healing or recurrences may be caused by persistent
      inflammation or by structural abnormalities at the nasofrontal connection. During
      the last decade endoscopic surgery (FES) has become a very useful method to
      restore the frontonasal drainage although long term results of this kind of
      population are rare. We evaluated the results of endoscopic surgery in two
      patient groups (total number of 50) both operated after prolongation (persistent
      symptoms after 4 weeks) of the initial acute phase of the frontal sinusitis. The
      first group (A, 15 patients, first trephined) was followed-up 4 years, the number
      of recurrences after the first FES was 60% and in the other group (B, no initial
      trephination) with over 6 months follow-up, 91% of patients had recurrences. In
      group A pre- and postoperative CT-scanning was used to determine the possible
      anatomical variations that could be causing the failures. All but 3 patients
      showed some kind of abnormal anatomical variation. In group B only preoperative
      CT was done. In most cases the reasons for recurrences of frontal sinusitis were
      polyps and/or chronic inflammation at the ethmoidal region.

PMID- 12526247
TI  - Sino nasal assessment questionnaire, a patient focused, rhinosinusitis specific
      outcome measure.
AB  - It is becoming increasingly important for clinicians to be able to demonstrate
      the effectiveness of their interventions. We have developed a rhinosinusitis-
      specific outcome measure (SNAQ-11) that avoids the shortcomings of the existing
      tools. This paper compares its use with the widely used Sinonasal Outcome Test
      (SNOT-20). We carried out a prospective study that involved forty patients
      undergoing endoscopic sinus surgery. Their SNAQ-11 and SNOT-20 scores were
      compared pre and post operatively. We also recorded individual symptom scores pre
      and post operatively in order to study the impact of surgery. The study shows a
      larger change in the postoperative SNAQ score compared to that in SNOT-20 (21%
      c.f. 11%) Although the pre and post-op changes in SNOT-20 are significant at the
      p = 0.005 level, the changes in the SNAQ-11 are highly significant at the p =
      0.0001 level. Furthermore we have statistically confirmed that the change seen
      with SNAQ-11 is larger in relation to the variation in change as compared with
      SNOT-20 (-1.08 c.f. -0.59). Our results show that SNAQ-11 is a valid and highly
      relevant rhinosinusitis outcome tool. The results also confirm that Endoscopic
      Sinus Surgery seems especially effective at addressing nasal obstruction,
      congestion and facial pain/pressure, fair at anterior nasal discharge, sneezing,
      hyposmia and sleep disturbance and poor for post nasal drip, cough and earache.

PMID- 12526248
TI  - The treatment duration of acute maxillary sinusitis: how long should it be? A
      nasal smear controlled study.
AB  - The aim of this study was to determine the most appropriate duration of treatment
      in acute maxillary sinusitis. The study was performed prospectively on 40 adult
      patients with acute maxillary sinusitis diagnosed by sinus puncture. Patients
      were randomized as to several treatment periods and treated by various
      antibiotics according to culture-sensitivity results. Patients in group 1
      received treatment for 7 days; groups 2, 3, and 4 received 14, 21, and 28 days,
      respectively. The patients were followed up with nasal smear findings on certain
      intervals during the 56-day follow-up period. Statistically significant
      differences were found beginning from the 21st day between group 1 and the other
      groups. However, there were no statistical differences among groups 2, 3 and 4.
      These findings show that the most appropriate duration of treatment in acute
      maxillary sinusitis should be at least 14 days according to nasal smear results.

PMID- 12526249
TI  - Flextube reflectometry and pressure-recordings for level diagnosis in obstructive
      sleep apnoea.
AB  - The objective of this study was to compare sound reflections in a flexible tube
      (flextube reflectometry) with pressure-catheter recordings (ApneaGraph) for
      identifying the predominant obstructive level of the upper airway during sleep.
      Seventeen males with suspected obstructive sleep apnoea syndrome (OSAS) were
      included in the study. The mean (standard deviation = SD) number of flextube
      narrowings per hour recording was 50.2 (20.4) and the mean (SD) RDI (respiratory
      disturbance index = apnoeas and hypopnoeas per hour recording) determined by the
      ApneaGraph was 45.7 (20.2). The mean difference (SD) between the number of
      flextube narrowings per hour recording and the RDIs determined by the ApneaGraph
      was not statistically significantly different from 0. There was no statistically
      significant correlation between the percentage of retropalatal narrowing of the
      total narrowing (retropalatal and retrolingual narrowing) measured by flextube
      reflectometry and the percentage of retropalatal ("upper") obstructive apnoeas
      and hypopnoeas of the total number ("upper", "intermediate" and "lower") measured
      by ApneaGraph (Spearman's correlation coefficient r = 0.24, p = 0.36, N = 17). In
      conclusion diverging results were found in flextube reflectometry studies and
      pressure-recordings performed on different nights regarding the level
      distribution of obstructions during sleep. Possible explanations of this
      discrepancy are discussed.

PMID- 12526250
TI  - Treating allergic rhinitis in the athlete.
AB  - Allergic rhinitis may affect athletes like any other member of society. It is a
      major problem for the atopic athlete. Either perennial or seasonal, it may cause
      problems with nasal function depending upon the type and quantity of allergen
      exposure. Moreover, exposure to irritants, chemicals and air pollutants may
      exacerbate allergic rhinitis. In this patient group, special diagnostic and
      particularly therapeutic considerations are warranted for the disease. Treatment
      of the athlete should be based on two important principles: no medication given
      should be on any list of doping products and no medication used should affect the
      athlete's performance. Antihistamines, topical cromolyn, and topical steroids may
      be used to control allergic rhinitis without violating 'anti-doping' regulations.

PMID- 12526251
TI  - Sphenochoanal polyp: diagnose and treatment.
AB  - Choanal polyps (CP) are benign mucous tumours that usually originate in the
      mucosa of the maxillary sinus, and hence are termed antrochoanal polyps. CP
      rarely originates in the mucosa of other nasal structures and paranasal sinuses.
      The purpose of this brief clinical communication is to present six cases of CP
      originating in the sphenoidal sinus and termed sphenochoanal polyps (SCP).

PMID- 12526252
TI  - Endoscopic treatment of so-called intranasal glioma.
AB  - Immunohistochemistry is useful to establish the pathological diagnosis of nasal
      glioma for which surgical excision is the unique treatment. Here we report a case
      of intranasal glioma found in a 5-month-old male patient. The tumor was
      successfully removed by endoscopic surgery. In the absence of a connection
      between the tumor and endocranial contents, we suggest to remove intranasal
      glioma by endoscopic surgery.

PMID- 12526254
TI  - Blindness following medial maxillectomy.
AB  - Medial maxillectomy via lateral rhinotomy approach is used in the treatment for
      tumours affecting the lateral nasal wall. The most frequent complications are
      crusting, epicanthal scarring and epiphora. The authors report a rare case of
      blindness secondary to indirect optic neuropathy following medial maxillectomy
      undertaken to treat a malignant melanoma arising in the lateral nasal wall. It is
      important to keep in mind, the possibility of this rare complication, while
      patients are being counselled preoperatively for medial maxillectomy.

PMID- 12526253
TI  - A rare location of bilateral inverted papilloma of the nose and paranasal
      sinuses.
AB  - Inverted papilloma is a rare benign sinonasal tumour, characterized by a
      potentially invasive nature. The lateral nasal wall represents the most common
      site of origin, whereas paranasal sinuses are involved by extension quite
      frequently. In contrast, primary sinus inverted papillomas have rarely been
      reported. Although the midfacial degloving approach has historically been the
      procedure of choice, recent technological advances have rendered endoscopic sinus
      surgery a safe procedure with equivalent success rates and low probability of
      papilloma recurrence. We present a rare case of bilateral inverted papilloma
      arising from the sphenoid septum and extending towards both the sphenoid and
      posterior ethmoid sinuses and the posterior section of both nasal cavities, while
      it slenderizes the sella turcica by compression and elevates the pituitary gland.
      The bilateral inverted papilloma was successfully removed with a transnasal
      endoscopic procedure. There is no evidence of recurrence for a follow up period
      of 1.5 years postoperatively. We conclude that it is a rare entity, which can be
      treated successfully with endoscopic sinus surgery in the hands of an experienced
      otorhinolaryngologist.

PMID- 12526255
TI  - Recurrent facial pain due to Pseudomonas aeruginosa sinusitis.
AB  - Pseudomonas (P) aeruginosa has been rarely reported as a causative agent of
      chronic sinusitis in otherwise healthy individuals, mostly as part of
      polymicrobial infections, while it has been frequently described among
      immunocompromised patients. We report a case of chronic maxillary sinustitis due
      to P. aeruginosa presenting as recurrent facial pain in a previously healthy
      middle-aged woman. Bacteriological diagnosis was established by tissue cultures
      and definitive treatment was achieved by surgical intervention and postoperative
      antibiotic treatment along with topical care.

PMID- 12526256
TI  - Rhinology resources on the Internet.
AB  - During recent years medical information through Internet is increasingly
      available to both patients and professionals and ever more biomedical resources
      become available on line to assist in clinical medicine, education and research.
      The purpose of this article is to present a detailed list of all the worldwide
      web sites of rhinology that are accessible through the Internet.

PMID- 12526258
TI  - A language of the soul. Reaching into the depths of dementia.

PMID- 12526259
TI  - Mom's last lessons. Living with Alzheimer's.

PMID- 12526260
TI  - Entering Donald's world. Creative interventions in Alzheimer's.

PMID- 12526261
TI  - Rising above despair. Finding hope beyond MS.

PMID- 12526262
TI  - I'm glad I have AIDS. One nurse's story. Interview by Carolyn Curtis.

PMID- 12526264
TI  - Why do our patients die in silence?

PMID- 12526263
TI  - A spirit set free. Learning about death from David.

PMID- 12526265
TI  - Let her go! Unafraid to die.

PMID- 12526266
TI  - Ritual for the dead. A prayerful approach to postmortem care.

PMID- 12526267
TI  - CPR on board the Metro.

PMID- 12526268
TI  - In light of eternity.

PMID- 12526269
TI  - Fish kisses & a new life. Mercy ship surgeries transform lives.

PMID- 12526270
TI  - Changes in the facial profile following insertion of complete dentures.
AB  - The effect of the topography of prostheses on the facial profile is poorly
      understood. This study was undertaken to identify changes in the facial profile,
      following insertion of dentures. The maxillary denture produced a more dominant
      effect than the mandibular, the greatest change affecting the philtrum and lips.
      The evidence also supports the concept that the tip of the upper incisors
      supports the lower lip. The actual length of facial tissues between selected
      landmarks in the midline did not change measurably following insertion of
      dentures in the rest position. A relationship between soft tissue shift and the
      known thickness of denture base was found for three landmarks, however, it was
      not possible to predict the size of these changes for other thicknesses of
      denture base with confidence.

PMID- 12526271
TI  - Repair versus replacement of defective direct composite restorations in teaching
      programmes in United Kingdom and Irish Dental Schools.
AB  - The teaching of the repair of direct composite restorations has been surveyed in
      United Kingdom and Irish dental schools. Based on a 100% response rate, the
      findings indicate that the vast majority of undergraduate students in United
      Kingdom and Irish dental schools are taught and gain clinical experience in the
      repair of direct composite restorations. There is general conformity with respect
      to the teaching in relation to operative techniques and materials used.

PMID- 12526272
TI  - Direct cores for vital teeth--materials and methods used to retain cores in vital
      teeth.
AB  - A core, or foundation restoration, is used to restore extensively damaged teeth
      to a form suitable for crown preparation. This literature review considers the
      range of materials which can be used for cores and the evidence for their
      suitability. The methods for their retention in vital teeth will be presented and
      appraised.

PMID- 12526273
TI  - The suitability of head-of-implant and conventional abutment impression
      techniques for implant-retained three unit bridges: an in vitro study.
AB  - This study compares the accuracy of master casts produced from impressions of
      implants using an abutment or a head-of-implant technique. The method used a
      Tandem Scanning Confocal Microscope to measure the dimensions of the gap between
      master casts produced by the two impression techniques and a custom made bridge.
      The median gap of 14 microns (interquartile range 10-17.9 microns) on the non
      screwed side of the abutment impression was greater than the median gap of 7.5
      microns (5-17.6 microns) for the head-of-implant impression and this difference
      was statistically significant (P < 0.005). In addition, the median gap on the
      screwed down side of the abutment impression of 10 microns, (6.3-12.1 microns)
      was greater than that of the head-of-implant of 5.5 microns (0.0-8.0 microns) and
      this difference was also statistically significant (P < 0.001). The head-of
      implant impression produced a more accurate fit than the conventional abutment
      impression.

PMID- 12526275
TI  - Force transmission in bar-retained implant-stabilised mandibular over-dentures:
      an in-vitro study.
AB  - The effects of attachment clips on force transmission in two implant-stabilised
      over-dentures with cantilever extensions were investigated, using a previously
      developed in-vitro model, which simulated functional mandibular deformation. Two
      retentive configurations were used: an avoid gold bar cranked anteriorly with 13
      mm distal cantilevers and the same configuration without attachment clips on the
      distal cantilevers. The dentures were loaded at individual tooth positions with a
      strain gauge beam and the forces exerted on the implants were measured using
      strain gauges mounted on their trans-mucosal abutments. The difference between
      the two retentive configurations was significant (P < 0.05) as tested by ANOVA.
      It is concluded that the retentive configuration without clips on the distal
      cantilevers results in a significant decrease in compressive forces on the
      implants.

PMID- 12526274
TI  - An in vitro assessment of the erosive potential of conventional and white ciders.
AB  - The aim of this in vitro study was to investigate the erosive potential of a
      range of traditional and white ciders using standard laboratory tests. It
      measured the pH, 'neutralisable acidity' and the amount of surface enamel lost
      following immersion over a period of 4 hours. The pH was measured with a digital
      pH meter and the 'neutralisable acidity' was measured as the volume of 0.1 M
      sodium hydroxide required to increase the pH to neutrality. Surface enamel loss
      was measured at 1, 2, 3 and 4 hours using profilometry. The pH on opening ranged
      from 2.96 to 4.04 and the 'neutralisable acidity' ranged from 14.54 to 21.47 mls.
      The amount of surface enamel lost following four hours immersion ranged from 8.60
      23.95 microns, compared to 12.85 microns for an orange juice control. All the
      ciders tested were acidic and had considerable erosive potential in vitro which
      was broadly similar to that of orange juice. A wide variation was found between
      different commercial brands and this information should be useful when
      counselling patients with tooth surface loss.

PMID- 12526277
TI  - Continuing education day 2002. The nursing shortage: status and solutions.

PMID- 12526279
TI  - American Nurses Association applauds JCAHO's focus on nursing shortage.

PMID- 12526278
TI  - Collaborative interdisciplinary team practice: a dream or reality?

PMID- 12526280
TI  - ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in
      patients with mild-to-moderate essential hypertension.
AB  - In this multicentre, prospective, randomized, open-label, blinded-endpoint
      (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40
      80 mg and enalapril 10-20 mg was evaluated using ambulatory blood pressure
      monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension.
      Patients were titrated to the higher dose of study drug at week 6 if mean seated
      diastolic blood pressure (DBP) was > or = 90 mmHg. The primary endpoint was the
      change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing
      interval after 12 weeks' treatment. Telmisartan and enalapril produced similar
      reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM
      periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced
      a significantly greater reduction in mean seated trough DBP, measured unblinded
      with an automated ABPM device in the clinic, amounting to a difference of -2.02
      mmHg (P < 0.01). A significantly greater proportion of patients achieved a seated
      diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05),
      also measured with the same ABPM device. Both treatments were well tolerated.
      Compared with telmisartan, enalapril was associated with a higher incidence of
      cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore,
      telmisartan may provide better long-term compliance and, consequently, better
      blood pressure control than enalapril.

PMID- 12526281
TI  - Is neuropathic ulceration the key to understanding increased mortality due to
      ischaemic heart disease in diabetic foot ulcer patients? A population approach
      using a proportionate model.
AB  - Ischaemic heart disease (IHD) is the commonest cause of death in diabetic foot
      ulcer patients and non-ulcerated diabetic patients, yet the mortality rate of
      diabetic foot ulcer patients is over twice that of non-ulcerated patients. As the
      cause of this increased mortality is not understood, we plotted the ratio of
      deaths due to ischaemic heart disease (IHDn) to other causes of death (i.e.
      IHDn:OCDn) against age for 242 diabetic foot ulcer patients and 121 controls (non
      ulcerated diabetic patients). The IHDn:OCDn ratio rose above 1.0 from age 40
      years onwards for diabetic foot ulcer patients, but from age 70 years onwards for
      controls, demonstrating differentially increased mortalities due to IHD. A
      population model involving summation of IHDn:OCDn ratios for neuropathic and
      neuroischaemic diabetic foot ulcer patients calculated an overall increased
      mortality rate of 1.8 compared with that of non-ulcerated diabetics. The model
      predicted that a 25% reduction in neuropathic diabetic foot ulcer patients dying
      from IHD would eliminate the increased mortality, demonstrating that neuropathic
      rather than ischaemic ulceration defines the cause of increased mortality among
      diabetic foot ulcer patients.

PMID- 12526282
TI  - Retrospective study of febrile seizures: subsequent electroencephalogram
      findings, unprovoked seizures and epilepsy in adolescents.
AB  - A retrospective questionnaire to determine the prevalence of febrile seizures was
      given to adolescents (16- and 17-year-olds) in the final 2 years of secondary
      school at the five schools in Alexandroupolis, Greece. Parents were interviewed,
      and clinical and electroencephalographic examinations were performed in all
      adolescents with a history of febrile seizures. Of 1708 adolescents, 56 (3.3%)
      had experienced at least one febrile seizure. Of these, 44 (78.6%) were simple
      and 12 (21.4%) were complex febrile seizures. Recurrent seizures occurred in 22
      cases (39.3%), and the mean age at onset was 25.1 months. There was a positive
      first-degree family history in eight cases (14.3%) and this increased to 27.3% in
      cases with recurrent seizures. Two of the adolescents (3.6%) had had one
      unprovoked seizure before the age of 3 years, and another two children developed
      epilepsy. Epileptiform electroencephalogram discharges were observed in only one
      case (1.8%) with generalized tonic-clonic epilepsy.

PMID- 12526283
TI  - Pharmacodynamics of menatetrenone and effects on bone metabolism in continuous
      ambulatory peritoneal dialysis patients.
AB  - Prevention of osteoporosis and renal osteodystrophy are important for the long
      term quality of life in dialysis patients. We examined whether administration of
      menatetrenone (vitamin K2) improves bone metabolism in continuous ambulatory
      peritoneal dialysis (CAPD) patients. Administration of a single dose of
      menatetrenone (15 mg) revealed that the 24-h pharmacodynamics in CAPD patients
      were comparable to those in control individuals. In a 12-month period of oral
      menatetrenone administration (45 mg/day), eight stable CAPD patients were studied
      for blood-bone metabolism parameters and for bone mineral content. Blood
      concentration of menatetrenone was detectable during the experiment period. Only
      at 12 months did active vitamin D3 and bone-type alkaline phosphatase (ALP) fall
      significantly, while total ALP rose significantly. Bone mineral density measured
      by dual-energy X-ray absorptiometry remained at the same level throughout the
      study period, suggesting that menatetrenone may protect against bone mineral loss
      in CAPD patients. These results show that the same dose of oral menatetrenone can
      be given to CAPD patients as to control individuals, and that menatetrenone can
      be used safely for 1 year in CAPD patients.

PMID- 12526284
TI  - Tumour necrosis factor-alpha levels in non-diabetic offspring of patients with
      type 2 diabetes mellitus.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is considered to be involved in the
      insulin resistance of type 2 diabetes mellitus. The offspring of patients with
      type 2 diabetes mellitus are at increased risk of developing diabetes and several
      metabolic abnormalities, but the underlying defects responsible are not known. We
      studied serum TNF-alpha levels in 30 healthy non-diabetic offspring of type 2
      diabetic parents (group A), and the relationship between TNF-alpha levels and
      variables associated with insulin resistance and diabetes. For comparison, 30
      healthy offspring of non-diabetic parents (group B) were also studied. The median
      serum concentration of TNF-alpha was significantly higher in group A than in
      group B, 3.5 pg/ml compared with 2.0 pg/ml, respectively. The individuals of
      group A also had significantly elevated levels of glycosylated haemoglobin,
      fasting glucose, glucose 2 h after an oral glucose tolerance test and
      triglycerides. We conclude that serum TNF-alpha concentration is significantly
      elevated in non-diabetic offspring of type 2 diabetics and this may predict later
      impairment of insulin action in these individuals.

PMID- 12526285
TI  - Comparison of tamsulosin and finasteride for lower urinary tract symptoms
      associated with benign prostatic hyperplasia in Korean patients.
AB  - Tamsulosin (0.2 mg) and finasteride (5 mg) once daily for 24 weeks were compared
      in a single-blind, randomized study as initial treatments for lower urinary tract
      symptoms associated with benign prostatic hyperplasia (BPH) in 205 Korean
      patients. Symptom and quality of life (QOL) assessment by the International
      Prostatic Symptom Score (I-PSS), maximum urinary flow rate (Qmax) and adverse
      events were analysed at 4 weeks and 24 weeks. On intention-to-treat analysis,
      both drugs showed similar efficacy at endpoint (decreased I-PSS, increased Qmax
      and improved QOL score; 34.7%, 23.9% and 34.1% for tamsulosin, and 30.5%, 22.2%
      and 23.1% for finasteride, respectively). However, tamsulosin produced
      significant improvements in I-PSS and Qmax at 4 weeks compared with finasteride
      (17.6% versus 10.0% and 10.9% versus 3.1%, respectively), and a superior QOL
      score improvement during the study. Adverse events were observed significantly
      more frequently among finasteride than tamsulosin patients (23 versus four). Both
      were equally effective in long-term treatment of urinary outflow obstruction
      symptoms associated with BPH in Korean patients, but tamsulosin was more
      effective for short-term treatment, with a better safety profile.

PMID- 12526286
TI  - Plasma concentrations of C-reactive protein and fibrinogen in ischaemic stroke.
AB  - This study investigated how fibrinogen and C-reactive protein (CRP) levels change
      in response to neural damage occurring after ischaemia, and the relationship
      between the distribution of the arterial lesion, the disease prognosis and the
      levels of these substances. Fibrinogen and CRP levels were measured in blood
      samples obtained from 83 patients admitted to hospital within 72 h of a first
      ischaemic stroke. The patients were evaluated clinically with the Glasgow Outcome
      Scale (GOS), and results were compared with 43 age-matched controls. The
      fibrinogen and CRP levels in unconscious patients with hemiparesis or hemiplegia
      were higher than those in conscious hemiplegic patients. Also, the difference in
      GOS values between the unconscious patients with hemiparesis or hemiplegia and
      conscious patients with hemiparesis or hemiplegia was statistically significant.
      Patients with large infarcts in the median cerebral artery and anterior cerebral
      artery had higher fibrinogen and CRP concentrations than the control group. In
      conclusion, fibrinogen and CRP may be important measures for determining the
      prognosis and outcome in patients following ischaemic stroke.

PMID- 12526287
TI  - Significance of p53 and bcl-2 immunoexpression in the prognosis of laryngeal
      squamous cell carcinoma.
AB  - This study was undertaken to determine whether p53 or bcl-2 immunoexpression has
      any significance in the prognosis of laryngeal squamous cell carcinoma. Eighty
      four cases of laryngeal squamous cell carcinoma at different pathological stages
      and locations were studied. All patients were treated surgically first, and
      followed up for 6-96 months (mean, 35 months). p53 and bcl-2 immunoexpression in
      tumour cells, evaluated by image analysis and histoscore, were found in 71.4% and
      46.4% of tumours, respectively. Glottic location was correlated with
      significantly longer survival than tumours at other locations. Pathological stage
      and histological grade of tumour were also significant predictors of survival.
      Neither p53 nor bcl-2 immunoexpression was found to be predictive of post
      operative survival. Only transglottic tumours expressed significantly high levels
      of bcl-2. Both methods used to evaluate p53 and bcl-2 immunoexpression correlated
      well with each other. This study suggests that immunoexpression of p53 and bcl-2
      is not a significant prognostic predictor in laryngeal squamous cell carcinoma.

PMID- 12526289
TI  - Modelling student age-groups in the subnational population projections for
      England: an investigation into potential improvements.
AB  - This article describes research aimed at improving modeling of student age-groups
      in the ONS subnational population projections for England. A number of data
      sources were investigated, and the research focused on Higher Education
      Statistics Agency data. Although the coverage of HESA data is not sufficient to
      enable student populations to be projected separately, the data have been used to
      devise an adjustment method for the student-age population. Both the data and
      method will be monitored and, if appropriate, used in future projections.

PMID- 12526288
TI  - Major surgery with Guillain-Barre syndrome: a case report.
AB  - Guillain-Barre syndrome (GBS) is an acute demyelinating polyneuropathy
      characterized by progressive muscle weakness and areflexia. The pathogenesis of
      GBS is unknown, but it is generally believed to result from aberrant humoral and
      cellular immune responses against components of the peripheral nervous system.
      The overall prognosis of GBS is quite good with approximately 85% of survivors
      making a good functional recovery. When a diagnosis of GBS has been made,
      appropriate treatment should be started as early as possible. This may include
      supportive care in intensive care units, ventilatory assistance, monitoring of
      blood pressure, fluid status, cardiac rhythm, nutritional supports and medical
      therapy. Our patient reached maximum deficiency 3 weeks after the onset of GBS.
      Full recovery took 8 months. The occurrence of GBS after major surgery is rare.
      We believe that major surgical stress may be the potential triggering factor for
      the occurrence of GBS in this case report.

PMID- 12526290
TI  - Changing economic and social roles: the experience of four cohorts of mid-life
      individuals in Britain, 1985-2000.
AB  - Men and women in Great Britain are increasingly involved in a variety of economic
      and social roles, particularly during their mid-life period. This article
      examines the changes in role occupancy across four birth cohorts passing
      throughout mid-life over the period 1985-2000. Data from the General Household
      Survey is used to investigate the occupancy of four key roles: 'partner',
      'parent', 'carer' and 'paid worker', analyzing separate and multiple role
      occupancies and level of commitment to a particular role. The implications of the
      findings for health and employment policies is also discussed.

PMID- 12526291
TI  - The decline of intensive intergenerational care of older people in Great Britain,
      1985-1995.
AB  - There are increasing concerns about the future availability of informal care for
      older people, particularly care by their children. This article explores past
      trends in the provision of informal care by children/children-in-law to their
      older parents/parents-in-law between 1985 and 1995 in Great Britain, using
      successive General Household Survey data. The article suggests that, during this
      period, there was a decline in co-resident intergenerational care and that this
      was associated with a decline in highly intensive intergenerational care. The
      article explores possible factors underlying these trends, in particular,
      demographic changes and changes in patterns of formal care for older people.

PMID- 12526293
TI  - [Detection of TTV DNA in liver tissues of patients with non A-G hepatitis by in
      situ hybridization].
AB  - OBJECTIVE: To demonstrate the existence of TT virus(transfusion-transmitted
      virus, TTV) in liver tissues of patients with unknown etiology. METHODS: Paraffin
      embedded liver tissues from 51 cases who were non A-E hepatitis serologically and
      immunohistochemically negative for HBsAg, HCV NS3 antigen and HGV NS5 antigen
      were tested by in situ hybridization with Dig TTV DNA probe. RESULTS: The total
      positive rate of TTV DNA was 27.5% (14/51). Among the different pathological
      types, the positive rates were 30.8% (4/13) in acute mild hepatitis, 12.5% (1/8)
      in acute fulminante hepatitis, 42.9% (3/7) in subacute fulminante hepatitis,
      33.3% (2/6) in chronic hepatitis, 22.2% (2/9) in active liver cirrhosis, 25%
      (1/4) in chronic fulminante hepatitis and 25% (1/4) in primary liver carcinoma
      respectively. Hybridization signals were detected within the nuclei or cytoplasm
      of the hepatocyte and most of them in nuclei. The positive cells were diffusely
      scattered in the intralobular areas in acute hepatitis and aggregated in
      periportal areas in chronic hepatitis or in the form of clustering in
      pseudolobules in active liver cirrhosis. CONCLUSION: Our results suggest that the
      TTV detected from liver tissues or sera from patients with unknown etiology is a
      novel virus, which belongs to hepadnavirus.

PMID- 12526292
TI  - [Eukaryotic expression, purification and analysis of the fusion protein of Epo
      Tpo(C)].
AB  - OBJECTIVE: To further elucidate the function of Tpo(C) and create a new type of
      Epo. METHODS: Tpo(C) was linked to Epo to produce a fusion protein--Epo-Tpo(C).
      The fusion gene was expressed in CHO cell. After selection with G418, Epo-Tpo(C)
      expressing cell lines was obtained. The supernatant had 15 U/ml Epo activity. The
      results of PCR and Southern Blotting indicated the fusion gene was fused into the
      genome. RT-PCR and RNA Dot Blotting analysis found the Epo-Tpo(C) mRNA. The
      supernatant was purified with Blue-Sepharose CL-6B. RESULTS: The rate of recovery
      was 94%. The in vivo activity tested by reticulocytes was 20% higher than ELISA.
      The half-life was about 12 hours while the Epo standard sample had half-life of 8
      hours tested with ELISA in rat. CONCLUSION: The results proved that Tpo(C) could
      protect Epo and improve its function. The fusion protein had satisfactory effect
      in the model of rat renal failure.

PMID- 12526294
TI  - [Study on expression of Fas/FasL and HBV antigens in liver tissue of patients
      with hepatitis B].
AB  - OBJECTIVE: To evaluate the role of apoptosis mediated by Fas/FasL in the liver of
      hepatitis B and the expression status of Fas, FasL, and HBV antigens. METHODS: We
      studied the expression of Fas antigen, Fas-ligand (FasL) and hepatitis B
      virus(HBV) antigens(HBsAg and HBcAg) in the livers of 62 patients with hepatitis
      B using immunohistochemistry ABC method. Six normal liver samples were used as
      control. RESULTS: Hepatocytes in normal liver had no Fas/FasL expression, but in
      the cases of hepatitis B, Fas was expressed mainly in the cytoplasm in 58
      cases(93.5%); FasL was observed in infiltrating mononuclear cells and in the
      cytoplasm of hepatocytes in 37 cases (59.7%). The expressions of Fas/FasL were
      closely related to the liver histological inflammation degrees. CONCLUSION: The
      apoptosis mediated by Fas/FasL may play an important role in the hepatocellular
      injury in hepatitis B. No correlation was found between the degrees of Fas/FasL
      expression and the presence of HBsAg and HBcAg in the liver.

PMID- 12526295
TI  - [Serological and pathological follow-up studies of the patients with single GBV
      C/HGV RNA infection].
AB  - OBJECTIVE: To elucidate the pathogenicity of GBV-C/HGV in causing viral
      hepatitis. METHODS: The sera and bioptic liver tissues, which involved 8 cases of
      the second liver puncture with an interval of 2 years, from 24 cases of single
      GBV-C/HGV RNA positive patients were observed for more than 2 years. GBV-C/HGV
      RNA in the sera and liver tissues was detected by using RT-PCR and in situ
      hybridization, respectively. Under light and electron microscope, the pathology
      of the liver tissues was observed. RESULTS: At the beginning of the observation,
      the mean serum alanine transaminase(ALT) level was 60.17 IU/ml(range, 42.00-87.00
      IU/ml), and the positive rates of anti-E2 antibody and GBV-C/HGV RNA in the sera
      and NS3 and/or NS5 in the liver tissues were 4.17%, 75.00% and 54.17%,
      respectively. In all the examined specimens, 79.17% of them showed mild acute or
      chronic hepatitis, mainly presenting with degeneration of hepatocytes, mild
      portal inflammation. GBV-C/HGV RNA and its NS3 and/or NS5 antigens were mainly
      detected in hepatocytes and a few mononuclear cells. In contrast, after more than
      2 years, the natural change rate (negative rate of GBV-C/HGV) of 24 cases was
      66.67% (P < 0.001). 75.00% had normal ALT level (P < 0.001) and 41.67% of anti-E2
      antibody in the patients was positive (P < 0.001). Through histological
      observation, besides 2 cases of liver tissues showing very mild hydropic
      degeneration, there were no abnormal findings in 8 cases of the second liver
      biopsy. CONCLUSION: GBV-C/HGV could induce mild and self-limited hepatitis, which
      showed that GBV-C/HGV may be a light and self-limited pathogenic agent to human
      liver. E2 antibody appearance may indicate a recovery and provide a protection
      from GBV-C/HGV infection. Whether there is any other recovery marker in serum
      requires further study.

PMID- 12526296
TI  - [Prokaryotic expression of hepatitis C virus envelope 1 gene and application of
      the expressed product].
AB  - OBJECTIVE: To express the HCV E1 gene in E. coli cells and to demonstrate its
      clinical significance in detection of anti-HCV E1 antibodies. METHODS: The
      expression vector was constructed by ligation of HCV E1 sequence, which was
      amplified by RT-PCR methods from 50 microliters of HCV RNA positive serum using
      primers specific to the HCV E1 sequence, to the prokaryotic expression vector PMS
      31b transfected POP2136 at 16 degrees C for 16 hours. The recombinant plasmid was
      screened out and characterized by restriction enzyme analysis. The bacteria
      containing the recombinant plasmid was induced at 42 degrees C for 4 hours, and
      the recombinant protein was visualized by SDS-PAGE. The specificity of the
      recombinant protein was determined by Western blot assay. After purification of
      the expressed protein, this protein was coated on the plate with the
      concentration of 2 micrograms/ml in pH 9.6 buffer at 4 degrees C for overnight,
      and the serum specimen was tested at the dilution of 1:20 by ELISA. RESULTS:
      There were 2 fragments could be seen on the SDS-PAGE after digestion of the RT
      PCR product with Sma I. And there emerged one fragment of 356 bp after digesting
      the recombinant plasmid with Sma I and Xba I. A band of 30,000 could be seen on
      the SDS-PAGE after the induction of bacteria containing the recombinant plasmid
      pMS-E1 at 42 degrees C for 4 hours. The Western blot assay showed that the
      expressed band could react with the anti-HCV positive serum. The ELISA result
      indicated that there were 28.9% (26/90) anti-HCV positive serum were anti-HCV E1
      positive, but 3.9% (3/76) were positive in the anti-HCV negative serum.
      CONCLUSION: The HCV E1 sequence from HCV RNA positive serum has been expressed in
      E. coli. The expression rate is about 17% of the total protein of the bacteria.
      This protein possessed good specificity and may be used in the diagnosis of HCV
      infection.

PMID- 12526297
TI  - [Detection and partial nucleotide sequence analysis of hepatitis G virus in sera
      of patients with hepatitis in Guangzhou].
AB  - OBJECTIVE: To investigate hepatitis G virus (HGV) infection in hepatitis patients
      and the gene type of HGV in Guangzhou. METHODS: Reverse transcriptase-nested
      polymerase chain reaction(RT-nested PCR) method using primers locating in
      noncoding region of HGV genome was used for detecting HGV RNA in sera of
      hepatitis patients and the amplified products were directly sequenced. RESULTS:
      25 cases were HGV RNA positive in 251 sera of acute and chronic hepatitis(9.96%),
      of which 4 cases were positive in 56 sera with hepatitis non A-E(7.14%), 8 cases
      were positive in 77 sera with hepatitis B (10.39%), 13 cases were positive in 118
      sera with hepatitis C(11.17%). The identity of nucleotide sequence was 98.0%
      between 2 Guangzhou HGV isolates, both were 91.1% with American isolate, 81.7%
      and 84.2% respectively between 2 Guangzhou isolates and African isolate.
      CONCLUSION: HGV infection exists in hepatitis patients, 2 Guangzhou HGV isolates
      may belong to the same gene type and both of them have a high homology with
      American HGV isolate.

PMID- 12526299
TI  - [Detection of TT virus DNA and sequence analysis of TTV gene in sera from young
      children in Nanjing].
AB  - OBJECTIVE: To investigate the prevalence of TTV genomes in young children from
      Nanjing and establish the PCR method for detecting TTV DNA. METHODS: A hemi
      nested polymerase chain reaction (PCR) assay was established to detect TTV DNA in
      110 young children and two PCR-amplified products were sequenced and the data
      were analyzed with the computer programs. RESULTS: TTV DNA was detected in 14 out
      of 110 children, and 222 bp sequences of 2 isolates from the children were
      analyzed. Compared with representative of published isolates, they have the
      nucleotide identity of 93.7%-98.6% with TX011. CONCLUSIONS: The infection rate of
      TTV in children is 12.73%, and 2 isolates from children belong to subgroup G1b.
      Our results indicates that TTV could be transmitted via other pathway besides
      hematogenous one, and TTV could be carried by healthy population.

PMID- 12526298
TI  - [Detection of TTV DNA and TTV IgG in 328 serum samples].
AB  - OBJECTIVE: To investigate the prevalence of TT virus(TTV) in a variety of
      populations in China. METHODS: TTV DNA and anti TTV IgG were simultaneously
      tested by PCR and ELISA. RESULTS: The positive rate of TTV DNA in the samples of
      81 normal subjects, 92 blood donors, 123 hepatitis A-G patients and 32 hepatitis
      non A-G patients were 2.5%, 2.2%, 19.5% and 28.1%, respectively; and anti-TTV IgG
      was 1.2%, 3.7%, 26.8% and 34.4%, respectively. There were significant differences
      between the normal and the blood donor group and the hepatitis group; and among
      multi-infectious cases, the infection rate of TTV with HBV was as high as 75.0%.
      CONCLUSION: The investigation indicated that TTV infection was very popular in
      different groups. Some of the normal and blood donor groups infected with TTV
      could become healthy carries of virus. And the hepatitis patients were the high
      risk group. In addition, TTV may be transmitted via other pathways besides blood.

PMID- 12526300
TI  - [Detection of TTV DNA from high background nuclear acid samples using specific
      nuclear acid captured-polymerase chain reaction].
AB  - OBJECTIVE: To improve the amplification of non-specificity of TTV DNA detection
      using PCR from high background nuclear acids because of its low level in samples.
      METHODS: Specific nuclear acid captured PCR(SNAC-PCR) was established through
      capturing TTV DNA onto microplate with specific nuclear acid by means of avidin
      biotin system, then amplifying captured TTV DNA as usual. Its specificity was
      evaluated by comparing with the detection of routine extraction samples using
      nested-PCR with or without subsequent DNA sequencing in 10 samples of sera and
      liver tissues in pairs. RESULTS: Positive results were obtained using routine
      protocol in 4 and 9 out of 10 samples of the sera and the liver tissues
      respectively. The PCR products were proved to be specific using RFLP analysis
      with Kpn I. However, positive results were found in only 2/10 and 3/10 of samples
      of sera and liver tissue using DNA sequencing. The results of SNAC-PCR were the
      same as those of routine protocol with subsequent DNA sequencing. Furthermore,
      sharper electrophoresis bands were obtained. CONCLUSION: SNAC-PCR could
      dramatically increase the specificity of the detection of TTV DNA, especially in
      high background nuclear acid samples. It can be widely used in the detection of
      other pathogens with low seral level or in high background nuclear acid samples.
      The level of TTV infection might be over-evaluated by currently used TTV DNA
      detection when the PCR products were not confirmed by DNA sequencing.

PMID- 12526301
TI  - [Anti-virus effect of combination of attenuated measles virus with 3TC on duck
      hepatitis B model].
AB  - OBJECTIVE: To evaluate the anti-virus effect of combination of attenuated measles
      virus with 3TC on duck hepatitis B model. METHODS: Guanzhou brown spot ducklings
      infected with DHBV were divided into three groups. Drug treatments including
      measles vaccine, 3TC and both measles vaccine and 3TC were given in the 13th day
      after the infection, respectively. Serum samples were obtained from all ducklings
      before, during and after treatment at different times and stored at -70 degrees
      C. DHBV DNA was detected by Dot-blot hybridization. RESULTS: Compared with the
      levels of DHBV DNA before and after treatment, no statistic difference was found
      in group of 3TC alone. The levels of DHBV DNA were not changed in group of
      measles vaccine alone in early stage, but decrease of DHBV DNA occurred after
      stopping treatment (comparison of the levels T13 with before treatment and T13 of
      positive group, P < 0.01 and P < 0.05, respectively). DHBV DNA level in group of
      measles vaccine combined with 3TC was obviously lower at 5th day after the
      treatment than in both measles vaccine and 3TC alone groups at the same time(P <
      0.05 and P < 0.01, respectively), and it remained low when the treatment was
      discontinued. CONCLUSION: Attenuated measles virus combined with 3TC may have
      early and long-lasting inhibiting effect on the replication of DHBV.

PMID- 12526302
TI  - [Antigen sandwiched ELISA for detection of total HIV antibodies].
AB  - OBJECTIVE: To establish a sensitive antigen sandwiched ELISA(AS) for detection of
      the total antibodies to HIV-1/2. METHODS: Based on the gene sequence of HIV-1/2
      type and its coded amino acid structure, 5 polypeptides were synthesized as
      coated antigens using solid-phase method. These polypeptides were labelled with
      horseradish peroxidase. And the total antibodies of HIV-1/2 were detected with
      the same method. RESULTS: These reagents were detected by three batches of HIV
      panel from The National Institute for the Control of Pharmaceutical and
      Biological Products (NICPBP). The results indicated that the corresponding rate
      was 100%. The variant coefficient rate was less than 10%. A comparison of antigen
      sandwiched ELISA with indirect ELISA in detection of a panel(20 positive sera and
      20 negative sera) from the NICPBP showed that the general coincident rate of
      indirect ELISA was 92.5% and the sandwiched system was 100%. The HIV-AS
      diagnostic reagent kits have passed the quality examination of NICPBP. A
      comparison of antigen sandwiched ELISA with Yapei reagents in detection of 90
      normal sera and 88 positive sera for HIV-1/2 showed that the coincident rate was
      100%. The reagents were stable at 37 degrees C for 4 days. This indicated that
      our reagents were highly specific, sensitive and stable. CONCLUSION: Our antigen
      sandwiched ELISA reagent for total antibodies of HIV has a merit of sensitivity
      specificity and stability. It can be clinically used for detection of HIV-1/2
      infection and in blood bank for the screening of blood donors.

PMID- 12526303
TI  - [Study on HIV DNA of epidemic HIV-1 strains].
AB  - OBJECTIVE: To study the characteristics of variation of HIV DNA in prevalent HIV
      1 strains. METHODS: HIV DNA, extracted from peripheral blood mononuclear
      cell(PBMC) in 63 patients infected with HIV, was investigated by reverse
      transcript PCR (RT-PCR), Long-Distance PCR(LD-PCR), molecular cloning
      hybridization and sequencing, respectively. RESULTS: The subtypes were identified
      in 57 samples. Subtype B was identified in 43 cases, subtype C in 5 and subtype E
      in 9. It was found that both full-length and defective HIV DNA in 31 out of 57
      cases, defective HIV DNA in 19 cases and full-length HIV DNA in 7 cases. The
      deleted regions of genome were from 71 to 7,759 nucleotides. CONCLUSION: The
      variation of gene segments of HIV DNA plays an important role in the infection
      and epidemic of HIV.

PMID- 12526304
TI  - [Preliminary investigation of the relationship between liver lesion and relevant
      factors in young children with rotavirus diarrhea].
AB  - OBJECTIVE: To investigate the possibility of liver lesion and its relationship
      with the relative factors in young children with rotavirus(RV) diarrhea. METHODS:
      The values of ALT and AST in sera of young children with RV diarrhea were
      measured to be compared with those of common diarrhea and were analyzed with the
      multifactors about diarrhea. The genomes of RV from blood serum were tested with
      reverse-nest polymerase chain reaction. RESULTS: Of the 41 young children with RV
      diarrhea, 15(36.6%) and 32 cases (75.6%) were abnormally higher in the level of
      ALT and AST respectively and both the ratio and degree of increase were
      significant in comparison with that in control group. There was no significant
      relation between the changes of the values of ALT and AST and the clinical
      manifestation of diarrhea. 4 out of 41 cases were found to be positive of
      viremia. CONCLUSION: RV infection might spread from intestine to blood and to
      other organs resulting in viremia, and the liver may be one of the organs
      involved.

PMID- 12526305
TI  - [Etiological study on human rotavirus infections in children with acute
      gastroenteritis].
AB  - OBJECTIVE: To understand the etiology of human rotavirus infections in children
      with acute gastroenteritis in China. METHODS: The investigation covered 1968
      feces infants and children with acute gastroenteritis in 19 provinces and cities
      in China. Feces samples collected from 1968 infants and children with diarrhea,
      148 children, 135 newborns and 37 adults without diarrhea, 36 adults with
      diarrhea were examined by polyacrylamide gel electrophoresis (PAGE). 1493 feces
      samples were examined by ELISA; 388 feces samples from sick children and 57 feces
      samples from children and adults without diarrhea were examined by EM. Bacterial
      culture were analyzed in 645 feces samples. RESULTS: Human rotavirus RNA (HRV
      RNA) was detected in 804(40.9%) of 1968 feces samples examined. No virus was
      detected in the feces samples of children and adults without diarrhea. Rotavirus
      antigen was detected in 500 (33.5%) of the 1493 feces samples. According to the
      genome profile of PAGE, 801 (99.6%) of the 804 rotavirus RNA positive belonged to
      group A virus, and the other 3 (0.4%) belonged to group C virus. According to the
      different migration of 10 and 11 segments on PAGE, the RNA pattern of group A
      rotavirus could be subdivided into two patterns: long and short patterns. The 527
      (66.8%) positive HRV RNA was in the long pattern, while the 267 (33.3%) positive
      were in the short pattern. Among the rest 6 appeared to be mixed types, and the
      examined one was uncertain. Four different genotypes of HRV RNA in long and short
      patterns were identified respectively. They were types 4232, 4222, 3232 and 3222.
      The eight electropherotype genomes of HRV RNA varied not only in different years
      or seasons but also with the ages of patients and regions where the patients
      live. CONCLUSION: Rotavirus infections are the major cause of diarrhea of infants
      and young children throughout China.

PMID- 12526306
TI  - [Immune response of mice to replication-defective recombinant adenovirus
      containing glycoprotein gene of rabies virus 3aG strain].
AB  - OBJECTIVE: To evaluate the immune response, of mice immunized with E1, E3 deleted
      replicative deficient recombinant adenovirus which can express glycoprotein of
      Chinese 3aG rabies virus. METHODS: Rapid fluorescent focus inhibition test
      (RFFIT) was used to determine the titer of neutralizing antibodies; specific
      antigen induced spleen lymphocyte proliferation was determined by in vitro 3H-TdR
      in-corporation assay, and lethal intracerebral challenge with CVS rabies virus
      was used to evaluate the protective effectiveness of the recombinant virus as
      candidate vaccine. RESULTS: Mice immunized by 1 x 10(7) recombinant virus
      developed high levels of rabies virus neutralizing antibodies (VNA). The spleen
      lymphocyte of the immunized mice also demonstrated remarkable increased
      proliferation after stimulation with inactivated rabies virus; 70%-90% of the
      mice immunized by the recombinant virus were protected from lethal intracerebral
      challenge with CVS rabies virus. CONCLUSION: E1, E3 deleted replication defective
      recombinant adenovirus containing 3aG glycoprotein gene may be developed as
      effective rabies vaccine to control rabies in China.

PMID- 12526307
TI  - [Study on specificity of IgM antibody response in patients with coxsackie virus B
      infection].
AB  - OBJECTIVE: To study the specificity of IgM antibody response in patients with
      Coxsackie virus B infection. METHODS: A Coxsackie virus B specific immunoblot
      assay was established for detection of CVB IgM antibody response in patients with
      recent CVB infection. RESULTS: Of 28 patients' serum samples, positive by ELISA
      captured CVB IgM test, analysis results of specific IgM response defined by
      immunoblot assay revealed VP1 protein specific which was crossly reactive among
      CVB group. CONCLUSION: This finding suggested that VP1 protein in Coxsackie virus
      B group potentially functioned as a predominant antigen inducing detectable IgM
      antibody following CVB infection.

PMID- 12526308
TI  - [Amino acid sequence analysis of peptides that can react to the nuclear
      localization signals of human cytomegalovirus PPUL44].
AB  - OBJECTIVE: To find the peptides that have strong binding ability to the nuclear
      localization signals (NLS) of human Cytomegalovirus (HCMV) PPUL44 protein, and to
      analyze their amino acid sequences. METHODS: Peptide clones that have binding
      ability to the NLSs were selected from a random peptide display library by using
      synthesized HCMV PPUL44 NLSA and NLSB respectively. The DNA sequences of these
      clones were detected by using "ABI Prism BigDye Terminator Cycle Sequencing Ready
      Reaction Kit". The amino acid sequences of the clones were analyzed for their
      homology, and the homologous sequences were compared with known sequences in
      protein bank. RESULTS: The peptides that can bind to the HCMV PPUL44 NLSA(named
      as bNLSApep) have higher homologous amino acid sequence to importin alpha
      subunit, the bNLSApep48 sequence AVVTPVLTEILK is more similar to the sequence of
      the importin alpha subunit Arm 7 from amino acid 18 to 29, ANIFPVLTEILQ; The
      bNLSBpep 39 is similar to the sequence of all 8 Arm regions of importin alpha
      subunit from amino acid 10 to 21. CONCLUSION: It is possible that the HCMV PPUL44
      NLSA is a specific recognition site by importin alpha subunit, it can bind to the
      Arm 7 region of importin alpha subunit; HCMV PPUL44 NLSB is a non-specific
      recognition site for importin alpha subunit. This study provided an experimental
      data for the proposal that the Arm repeat region of importin alpha subunit is the
      binding region of NLS.

PMID- 12526309
TI  - [Formation of specific complex of SV40 large tumor antigen and p53 in human brain
      tumors].
AB  - OBJECTIVE: To study the interaction of SV40 early region gene coding product, the
      large tumor antigen(Tag) with tumor suppressor p53 in human brain tumorigenesis.
      METHODS: Tag was detected by immunoprecipitation and Western blot in 43 cases of
      human brain tumors and 5 cases of normal human brain tissues. Tag-p53 specific
      complex was screened in 18 Tag positive cases. RESULTS: Tag was found in all of 5
      ependymomas and 2 choroid plexus papillomas, as well as in pituitary adenomas
      (5/6), astrocytomas (7/10), meningiomas (4/6), glioblastomas multiforme (3/5) and
      medulloblastomas (2/5). None of the 5 normal brain tissues were positive for Tag,
      nor were 3 oligodendrogliomas and 1 pineocytoma. Tag-p53 complexes were found in
      all of 18 Tag positive cases. CONCLUSION: SV40 Tag can form a specific complex
      with p53 in human brain tumors, the inactivation of p53 due to the formation of
      Tag-p53 complex may be one of the important mechanisms of human brain
      tumorigenesis.

PMID- 12526310
TI  - [Investigation of group A rotavirus infection in several cities in China and
      prevalence of VP7 serotype].
AB  - OBJECTIVE: To study the prevalence of Group A rotavirus infection in China.
      METHODS: 374 samples from infants with diarrhea were collected from six cities
      (Beijing, Shenyang, Xinxiang, Shanghai, Shenzhen and Guangzhou) in autumn and
      winters of 1997 and/or 1998. The incidence of rotavirus infection and the
      prevalence of the four dominant serotypes G1, G2, G3, G4(VP7 serotype) were
      detected by PAGE and RT-PCR. RESULTS: Of the 374 samples detected, 181 were
      rotavirus positive. The positive rate was 48.4%, ranging from 32%-63% in
      different cities. The positive rates between 1997 and 1998 in Beijing and
      Shanghai were similar. Serotyped by RT-PCR method based on VP7 sequence, the
      positive rates of type G1, G2, G3 and G4 was 89.5%, 6.1%, 2.8% and 0,
      respectively. Two cases were found being coinfected with G1 and G2, and one case
      was confirmed to be infected with G9 by cDNA sequence analysis. There was a
      little difference in prevalence of G type rotavirus infection among samples from
      different cities and different years. CONCLUSION: The results indicated that
      rotavirus was the most important etiologic agent in this country, and the
      predominant serotypes were G1, G2 and G3.

PMID- 12526311
TI  - [Prospective study of combination of interferon-alpha with ribavirin for
      treatment of chronic hepatitis C in children].
AB  - OBJECTIVE: To explore more efficacious therapy for chronic hepatitis C in
      children. METHODS: With combination of recombinant interferon-alpha/ribavirin
      therapy, we treated 15 children, with viral sera and biopsy-proven chronic
      hepatitis C, who did not respond to the treatment of interferon-alpha alone and
      had frequently relapse, with the disease courses of 5-9 years (mean 4.5 years).
      Mean age of the children (12 males and 3 females) was 6.8 years (6 months-10
      years). 14 patients had blood transfusion history. RESULTS: HCV RNA in 12
      patients was negative after combined treatment of 3 months (1.5-5 months). None
      of the patients treated had skin rash and severe adverse reaction. Transient
      fever and influenza-like symptoms with combined therapy were similar to those
      with interferon-alpha therapy alone. Hemoglobin level decreased slightly in 9
      patients (mean decrease by 5 g/L; max, 20 g/L). Reticulocytes elevated slightly.
      White blood cells, platelets, Bun and Cr were normal in all the patients.
      CONCLUSION: Our results show that combination of interferon-alpha with ribavirin
      for treatment of hepatitis C in children is efficacious, safe and reliable. It
      deserves popularization.

PMID- 12526312
TI  - [Experimental study of the virus inhibitory effect of chuan-kang-ping granule].
AB  - OBJECTIVE: To explore the virus inhibitory effect of Chuan-Kang-Ping Granule.
      METHODS: Using tissue culture technique, the maximal non-toxic concentration of
      the drugs in Hep-2 cell culture were measured and the virus inhibitory index of
      the drugs on the respiratory syncytial virus (RSV), the coxackie B3 virus (Cox
      B3) and the influenza A1 virus (A1) was calculated. In addition, the degrees of
      inhibition of the drugs on the cytopathic effect of viruses in cell culture was
      observed by changing sequence of adding the viruses and the drugs. RESULTS: The
      maximal non-toxic concentration of Chuan-Kang-Ping Granule was 1:16. The virus
      inhibitory index on RSV, CoxB3, A1 was 8.8 and 2, respectively. The maximal non
      toxic concentration of Shuang-Huang-Lian oral administration Liquid was 1:32. The
      virus inhibitory index on RSV, CoxB3, A1 was 8, 16 and 2, respectively. The
      degrees of cytopathic effect were different when changing sequence of adding the
      viruses and the drugs. CONCLUSION: Chuan-Kang-Ping Granule inhibited the
      replication of RSV, CoxB3, A1 in cultured cells. The inhibitory effect of the
      drugs were the same or nearly the same with Shuang-Huang-Lian oral administration
      liquid. The mechanism of the inhibitory effects of the drugs on the viruses was
      probably the direct killing effect in vitro, or the drugs might inhibit some key
      link of the replication of the viruses in cultured cells.

PMID- 12526313
TI  - [Observation on the effect of GM-CSF and alpha-INF joint treatment on chronic
      hepatitis B].
AB  - OBJECTIVE: To observe the effect of GM-CSF and alpha-INF joint treatment on
      chronic hepatitis B. METHODS: GM-CSF treatment combined with alpha-INF was set up
      as experimental group and alpha-INF alone as the control. At the same time, we
      counted the blood leukocytes, monocytes and granulocytes of the patients.
      RESULTS: The short-term and long-term effective rates of the experimental group
      were 61% (11/18) and 67% (12/18) respectively, while those of the control group
      were 44% (8/18) and 33% (6/18) respectively. The leukocyte, monocyte and
      granulocyte counting in blood of patients treated with GM-CSF and alpha-INF
      increased significantly. CONCLUSION: GM-CSF and alpha-INF joint treatment is
      effective for chronic hepatitis B. The mechanism may be related with the
      increasing number of monocytes in blood, hence to improve the antigen delivering
      ability.

PMID- 12526314
TI  - [Membrane protein Fas/FasL system in viral infections].

PMID- 12526315
TI  - [The significance of interferon sensitivity determining region in interferon
      therapy of hepatitis C].

PMID- 12526316
TI  - [Cloning and sequencing of adenovirus type 7 vaccine strain 76.5-87 mu fragment].
AB  - Adenovirus 7(Ad7) vaccine strain has been used more than 30 years in US army
      recruits for prevention of Ad7 infection and has been proven to be safe and
      effective. Recent years more attention has been paid to exploring the
      possibilities of using it for gene therapy or making recombinant vaccine. In
      order to construct adenovirus 7 vector, Ad 7 vaccine strain 76.5-87 mu fragment
      was cloned and sequenced. The fragment contains 3,557 bp which encodes 6 proteins
      of E3 region, namely 12.1 kD, 19.2 kD, 20.1 kD, 20.5 kD, 10.3 kD and partial of
      15.2 kD. Nucleotide sequences of all these proteins show a high homology with the
      corresponding region of human adenovirus prototype strain Ad 7(Ad 7p) and Ad
      7h(the homology of nucleotide sequence of the 6 proteins is more than 97.2%). The
      equivalent of ORF 16.1 kD in Ad7p and Ad7h was mutation due to a base pair
      deletion. The region corresponding to ORF 7.7 kD in Ad7p was missing in Ad7v due
      to a deletion. The results should be helpful to the construction of Ad7v vectors.

PMID- 12526317
TI  - [Adeno-associated virus vector mediated gene transfer of HSVI-TK and its effect
      on killing cancer cell].
AB  - The plasmid pACTK-19 was constructed by inserting HSVI-TK gene into the multiple
      cloning sites of the general adeno-associated virus(AAV) vector pACR-Neo. When
      plasmid pACTK-19 was transfected to recombinant AAV's packaging cell line AE1201,
      which was exposed to Adenovirus 5 for two hours before transfection, we got
      rAAV/ACTK at the titer of 3.4 x 10(5) CFU/ml. After infecting human lung cancer
      cell A549 with rAAV/ACTK, we extracted host cell's chromosome cDNA and amplified
      part of the HSVI-TK sequence by a pair of HSVI-TK's primers and then hybridized
      to digoxin labelled HSVI-TK gene probe. We got corresponding positive band and it
      proved the integration of HSVI-TK into host cell's chromosome cDNA. By reverse
      transcripting rAAV/ACR-Neo infected A549 total cell RNA, we amplified part of
      HSVI-TK sequence and hybridized to Neo gene probe. The corresponding positive
      band demonstrated the expression of HSVI-TK. So through rAAV/ACTK, HSVI-TK was
      transferred into host cells and was expressed in them, the rAAV's genome was
      integrated into host cell's chromosome DNA. Connecting with Ganciclovir (GCV),
      the HSVI-TK gene transfer mediated by rAAV/ACTK, could inhibit the synthesis of
      chromosome DNA and lead to the killing of the lung cancer cell. This work proved
      that recombinant AAV could be used as vector for gene transduction to cancer
      cell, and also laid foundation for further research and application of AAV
      vector.

PMID- 12526318
TI  - [Functional phage display of human interferon alpha lc/86D].
AB  - We have successfully displayed human interferon-alpha lc/86D(IFN-alpha lc/86D) on
      the surface of the filamentous bacteriophage using a phagemid vector system
      (pCANTAB5E). The IFN-alpha lc/86D cDNA was fused to a DNA sequence encoding the
      amino-terminal domain of pIII, a minor coat protein exposed at one end of the
      phage. Fusion gene was packaged into phagemid particles upon superinfection with
      M13K07 helper phage. Expression of IFN-alpha lc/86D was verified by its
      reactivity with IFN-alpha l specific neutralizing antibodies and the phage
      displayed IFN-alpha lc86D was found to possess antiviral biological activity on
      VSV challenged WISH cells comparable to that of human recombinant IFN-alpha lb.
      These results demonstrate that IFN-alpha lc/86D can be displayed on phage in a
      correctly folded and functionally active form, and this system can be applicable
      to the sorting of a large repertoire of phage-displayed IFN-alpha lc/86D
      variants.

PMID- 12526319
TI  - [YY1 and its repressive effect on human papillomavirus 16 early promoter P97
      existed widely among human epithelial cell lines].
AB  - Cellular transcription factor YY1 represses the activity of early promoter P97 of
      HPV 16. Removal of the specific binding sites for YY1 in HPV 16 LCR can increase
      the P97 activity. To analyse the expression of YY1 and the existence of the
      activation effect on P97 due to removing YY1 binding sites in the LCR region, we
      extracted nuclear proteins from four cervical cancer cell lines and two human
      keratinocytes. EMSA assays were carried out in vitro. At the same time, we
      transiently transfected the luciferase reporter plasmids, which contain HPV 16
      reference and mutated LCR sequences, respectively, into the different cells and
      determined the luciferase expressions. The results showed that all the analysed
      cell lines contained biologically functional YY1 proteins. No remarkable
      difference in the concentration of native YY1 proteins could be detected among
      the tested cells. Removal of YY1 binding sites in HPV 16 LCR could elevate P97
      activity in several analysed cell lines, including normal human primary
      kerationcytes from foreskin. It suggests that YY1 regulatory system exists widely
      in human epithelial cell lines. We also found that the transcription activator
      NF1 was more highly expressed in C33a cell than in HT3 cell, indicating an
      unevenly distribution of functional proteins in various cell lines.

PMID- 12526320
TI  - [Seroepidemiologic survey for A/PR/8/34 (H1N1) virus from Chinese residents].
AB  - A total of 414 serum specimens were collected from the residents with ages of <
      or = 20 year old in eight different parts of China for detecting antibody to
      A/PR/8/34(H1N1) influenza virus with HI test. Of them, 24 had antibody with HI
      titers > or = 20 to A/PR/8/34(H1N1) virus. These 24 specimens were tested with
      the same method using A/swine/Iowa/15/30 (H1N1), A/Guangxi/10/94(H1N1) and
      A/Beijing/53/97(H1N1) viruses. The results showed that except 5 of them had
      antibody with HI titers 20-40 to A/Beijing/53/97(H1N1) virus, the rest had
      antibodies with titers < 20 to the viruses for checking test. Therefore, the
      antibody to A/PR/8/34(H1N1) virus in the tested sera was not caused by cross
      reaction of antibodies against another H1N1 viruses. The results in this paper
      also further demonstrated that the A/PR/8/34(H1N1) like virus was circulating in
      residents in China.

PMID- 12526321
TI  - [Detection of dengue virus genome RNA in some kinds of animals caught from dengue
      fever endemic areas in Hainan Island with reverse transcription-polymerase chain
      reaction].
AB  - Detection of dengue virus genome RNA in brain of bats caught from dengue fever
      endemic areas in Hainan Island were carried out with reverse transcription
      polymerase chain reaction(RT-PCR). Positive result was demonstrated in 20 of 35
      bats tested, with a positive rate of 57.14%; RT-PCR was applied for the detection
      of dengue virus genome RNA in sera of bats caught from the endemic areas in
      Hainan Island, 3(16.66%) of 18 sera were positive. Dengue virus genome RNA in
      female Aedes aegypti captured from dengue fever endemic areas in Hainan Island
      was detected by using RT-PCR, 1(33.33%) of 3 lots was positive. Similar
      examinations on bat brains and mosquitoes captured from non-endemic areas were
      all negative. In addition, monoclonal IgG antibodies against types 1-4 dengue
      viruses were added onto brain imprints of bats captured from endemic areas of
      dengue fever in Hainan Island, 16(80.00%) of 20 showed positive results for type
      2 dengue virus antigen by direct immunofluorescent assay. The antibodies to
      various types of dengue virus were coincided to that of dengue virus genome RNA.
      The above results proved that bat is the reservoir of dengue virus, and this
      provides an important clue for the effective control of dengue fever epidemics in
      endemic areas.

PMID- 12526322
TI  - [Gene cloning, expression and immunological identification of a single chain
      antibody fragment 3D3 against dengue type 3 virus].
AB  - Hybridoma 3D3 which secreted monoclonal antibody against Dengue type 3 virus was
      used to extract mRNA and then was reverse-transcripted into cDNA for amplifying
      heavy and light chain variable domain genes. The amplified light and heavy chain
      variable domain genes were connected by flexible linker to form a single chain
      antibody fragment (ScFv) gene of 750 bp, which was cloned into phage pCANTAB5
      vector using the recombinant phage antibody system. The ScFv gene was expressed
      as fusion protein with phage g3p coat protein and displayed on the phage surface.
      The phagemid was used to transform competent E. coli TG1 cells and then infected
      with M13K07 helper phage to rescue the phagemid and antibody ScFv gene. 12 of the
      20 randomized clones were shown to react with dengue type 3 virus by
      immunofluorescence.

PMID- 12526323
TI  - [Expression of human ScFv against human immunodeficiency virus type 1 gp120].
AB  - In order to generate human antibody against HIV-1, using synthetic peptide from
      HIV-1 gp120 v3 loop as antigen, we screened the recombinant phage antibodies by
      immunoaffinity and selected positive clones carrying anti-gp120 ScFv gene. The
      phage DNA was extracted and transformed to E. coli HB2151 that allowed to express
      soluble ScFv proteins by inducing of IPTG. The results of SDS-PAGE and Western
      blot showed that the molecular weight of the expressed product is about 28 KD and
      exhibited anti-c-myc activity. ELISA and Dot blot analysis displayed that the
      soluble ScFv specifically bound to gp120 and had a higher specificity and
      affinity. Competitive ELISA further demonstrated that the product was specific to
      gp120.

PMID- 12526324
TI  - [Detection of TT virus DNA and sequence analysis of partial gene of TTV in sera
      from blood donors].
AB  - In order to investigate TTV infection in blood donors, 262 sera samples from
      blood donors were detected by nested--PCR method using primers from ORF1 of TTV
      genome DNA. The results showed that 18 of 58(31.0%) serum samples from blood
      donors with elevated transaminase level were positive for TTV DNA. 30 of 204
      (14.7%) sera samples from blood donors with normal transaminase levels were
      positive for TTV DNA. There were significant difference between them (chi 2 =
      38.1, P < 0.05). Five products of PCR for TTV DNA were purified and cloned to T
      Vector. The sequence analysis showed that there were above 97% nucleotide
      identity among AB008394 (from Japan), TTVCHNI (from China) and our 5 isolates
      from blood donors. The results suggest that there exists TTV infection among
      blood donors in China. TTV may be transmitted by blood transfusion. Our isolates,
      AB008394 and TTVCHN1 share a same genotype.

PMID- 12526325
TI  - [Investigation on TT virus infection among various populations in Shenzhen].
AB  - A polymerase chain reaction assay with nested primers (nested PCR) deduced from
      the well conserved sequences of TTV ORF1 region was established to detect TTV
      DNA. PCR products from the 2 patients with non A-G hepatitis were cloned and
      sequenced to confirm its specificity. By using this assay, we tested the serum
      samples of 90 normal individuals, 88 paid blood donors, 79 intravenous drug users
      and 29 patients with non A-G hepatitis in Shenzhen, China. The positive rates of
      TTV DNA were 7.8%, 9.0%, 41.7% and 44.8%, respectively. TTV DNA was detected in
      14 of the 90 normal individuals and 88 paid blood donors without any symptoms of
      liver disease. The results of this study suggest that TTV infection is common in
      normal population and the paid blood donors. The intravenous drug users are at
      high risk for TTV infection. TTV would be responsible for a part of non A-G
      hepatitis.

PMID- 12526326
TI  - [Rapid construction of recombinant baculovirus carrying hepatitis B virus surface
      antigen gene by using a novel baculovirus shuttle vector(Bacmid)].
AB  - In order to express the HBV surface antigen (HBV) efficiently by using the Bac-to
      Bac system and to produce HBsAg for diagnosis and vaccine development of HBV, a
      recombinant donor plasmid pFB-BS carrying HBsAg gene was constructed. The gene
      was inserted into shuttle plasmid (Bacmid) in E. coli DH10Bac with the help of
      Tn7 transposition system. The recombinant Bacmid was examined by PCR and
      transfected to Sf9 cells. HBsAg was expressed under the control of polyhedrin
      promoter of baculovirus in insect cells and was identified by ELISA. The quantity
      of the expression reached to 2 micrograms/10(6) cells and most production was
      within cells. Our data suggested that the Bac-to-Bac system can be used
      successfully and rapidly in the expression of viral gene.

PMID- 12526327
TI  - [The relationship between expression of oncogene proteins and HBeAg in chronic
      hepatitis B virus infection].
AB  - To study the relationship between abnormal expression of oncogene protein and HBV
      replication, we detected the expression of protein products C-erbB-2 P185, ras
      P21 and tumorsuppressor gene product P53 and HBeAg in the serum of 64 patients
      with chronic HBV infection by using immunohistochemical technique and ELISA. The
      results were as follows. The positive detection rates of serum HBeAg in C-erbB-2
      P185 and ras P21 oncogenes positive groups were 89.4% and 84.6% respectively, but
      only 20% and 48% in C-erbB-2 P185 and ras P21 negative groups. It suggested that
      there is a close correlation between the over-expression of C-erbB-2 P185, ras
      P21 and replication of HBV.

PMID- 12526328
TI  - [Expression of Bcl-2 and Bax proteins in liver tissues of chronic viral
      hepatitis].
AB  - In order to study the significance of expression of Bcl-1 and Bax proteins in the
      liver tissues, 35 cases of chronic viral hepatitis (CH) were
      immunohistochemically studied. The results showed that Bcl-2 and Bax were mainly
      colocated in cytoplasm of the mononuclear cells(MN) in the areas of focal
      necrosis, bridging necrosis and piecemeal necrosis (PN). Some hepatocytes
      surrounding these areas expressed Bcl-2 and Bax or expressed Bax only.
      Pathological examination found that these hepatocytes Suffered from hydropic or
      acidophilic degeneration. In the severe viral hepatitis, survival hepatocytes
      also expressed Bcl-2 and Bax. It is suggested that the expression of Bcl-2 and
      Bax in the liver tissues correlated with the apoptosis of hepatocytes in CH and
      influenced the progress of severe viral hepatitis.

PMID- 12526329
TI  - [Study on quality of China made NS3 antigen].
AB  - Using anti-HCV antibody screening assay to control the quality for blood is the
      main measure for preventing transmission of HCV in China. This study is to
      evaluate the quality of NS3 antigen because of their positive rate to anti NS3
      antibody in HCV infected patients and to all kinds of anti-HCV antibody detecting
      kits, that need NS3 antigen. We collected four China genetically engineered NS3
      antigens and other two NS3 antigens came from abroad. The first step is to
      confirm that the antibody reactivity with coated NS3 antigen is true. The second
      step is to compare the quality of China made NS3 antigens with NS3 antigens
      abroad. The results showed that coated NS3 antigen kits have high sensitivity in
      identifying the positivity of sera from second generation panel, among them that
      were RIBA-2 indeterminate or negative. Some negative or false positive results by
      coated Chinese NS3 antigens indicate that manufacturer should make more efforts
      to ensure the best condition terms for using these antigens.

PMID- 12526330
TI  - [Study on the experimental infection of hepatitis G virus in rhesus monkey].
AB  - In order to study the experimental infection of HGV in rhesus monkey, the monkeys
      were infected using the plasma from a donor with HGV RNA positive. The second
      generation monkeys were infected with the sera of the first generation monkeys
      infected after 6 weeks, and also the third generation monkeys were infected with
      the sera of the second generation monkeys. HGV RNA were detected by RT-nPCR. The
      results showed that in sera of infected monkeys HGV RNA were positive after 1
      week of inoculation, and were consecutively positive for up to 28 weeks at
      longest. The level of ALT raised a little in monkey No. 1 and higher than 100 U/L
      in No. 5. The liver biopsy showed viral hepatitis--like histological changes.
      Comparing the sequence of HGV 5'LTR from sera of the infected monkeys and the
      blood donor, the homogeneity, to strain HGU44402 was 98.33% and 95.83% to strain
      HGU36380 was 92.50% and 89.17%, respectively. The results suggested that the
      rhesus monkey is sensitive to HGV and is suitable for establishment of an animal
      model.

PMID- 12526331
TI  - [Detection of hepatitis C virus and hepatitis G virus RNA by multiplex reverse
      transcription-polymerase chain reaction and microtiter plate reverse
      hybridization].
AB  - Multiplex reverse transcription-polymerase chain reaction for the simultaneous
      detection of HCV and HGV RNA has been established, in which primers were deduced
      from high conservative region of HCV and HGV and PCR amplicons were detected by
      microtiter plate reverse hybridization with HCV or HGV specific probe. Sequence
      analyses showed that amplicons of HCV were 93.1%-94.1% and 92.5%-93.7% of
      nucleotide homology compared with Takamizawa and Choo, and amplicons of HGV were
      90.7%-92.5%, 92.0%-92.1% and 94.3%-94.5% of nucleotide homology with Simons,
      Linnen and Chang. The detective sensitivity was 100 times over that of
      electrophoretic assay with single amplification. CVs of HCV and HGV were 8.9% and
      9.8%, respectively, and the optimal concentration of NaOH for hybridization was
      0.1-0.15 mol/L. The optimal time for hybridization was 30-50 minutes. The results
      of detection with multiplex PCR showed the presence of infection with HCV or HGV
      alone and coinfection with both % them.

PMID- 12526332
TI  - [Purification and identification of the bovine rotavirus receptor on MA104
      cells].
AB  - In this research the bovine rotavirus(BRV) receptor on MA104 cells was purified
      and identified. The monoclonal antibody(McAb) against BRV receptor was coupled
      with the CNBr-activited sepharose 4B. BRV receptor was purified from the MA104
      cell extracts by the method of the immunoaffinity chromatography. The results of
      the indirect ELISA ard the dot immunobinding assay showed that the BRV receptor
      antigenicity of the purified compound was positive. On SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE) the eluate from the column with the McAb coupled
      showed a single band, corresponding to the elution peak. The eluate from the
      column without antibody showed no such a band on SDS-PAGE. The result of Western
      blot showed the purified compound could be distinguished by the McAb against BRV
      receptor. Solid-phase assay showed the purified compound had the ability to bind
      BRV. The mouse immunoserum against the purified compound could block the BRV
      infection to its host cells. The experimental results above showed that the
      purified compound was the receptor for BRV.

PMID- 12526333
TI  - [Study on the anti-herpes simplex virus activity of a suppository or ointment
      form of Astragalus membranaceus combined with interferon alpha 2b in human
      diploid cell culture].
AB  - A study on the anti-herpes simplex virus activity of the suppository or ointment
      form of Astragalus membranaceus(AM) combined with recombinant human interferon
      alpha 2b(IFN) was carried out in human diploid cell culture. AM is a Chinese herb
      medicine and have been used in China as a tonic for thousands of years and the
      IFN was produced from E. coli with 95% purity. Obtained results indicated that
      the placebo suppository and ointment(without AM and IFN) seemed not to decrease
      markedly the anti-viral activity of IFN in WISH/VSV assay system. The anti-herpes
      simplex virus activities of suppository and ointment forms of AM and IFN were
      shown to be significantly higher than that of IFN alone. It is well known that
      chronic cervicitis is closely related to papillomavirus, cytomegalovirus as well
      as herpes virus infections. The AM-IFN suppository is suggested to be used in the
      treatment of cervicitis and the ointment in the treatment of skin herpes.

PMID- 12526334
TI  - [Establishment of a method for detecting anti-HCV IgM using recombinated
      structural region antigens].
AB  - Presence of IgM antibody to viral structural protein can be taken as the marker
      of its replication, so the detection method for anti-HCV IgM was established
      using as HCV recombinated structural region antigens, including C, E1, E2, as the
      coated antigen and rabbit anti-human gamma chain sera for neutralization and
      sheep anti-rabbit IgG coated for the sorbence of the complex of RAH-gamma with
      human IgG. 76 serum specimens of the hepatitis C patients were detected by
      indirect ELISA for anti-HCV IgM and by RT-PCR for RNA. The results suggested that
      IgM antibodies to C, E1, E2 were closely related with RNA (P < 0.005). The
      components of the IgM antibody, too were identified by indirect ELISA with
      recombined antigens coated respectively. When whole-fragment C or C + E2 were
      used as the coated antigens, anti-HCV IgM in 96.6% or 100% of serum specimens can
      be respectively detected. Using recombined structural region antigens, detection
      of anti-HCV IgM by ELISA was high sensitivity and specificity.

PMID- 12526335
TI  - [Purification of hepatitis B virus antigen and its application in detection of
      human serum antibody].
AB  - A recombinant plasmid DNA pBV220/eAg provided by professor Zhou Jian was
      transferred into DH5 alpha celes. The effectively expressed strain was harvested
      after cloning. It was then incubated in 30 degrees C for 3 hrs and 42 degrees C
      for 6 hrs, the HBeAg protein was induced. After purification of the protein by
      DEAE-Sepharose Fast Flow chromatography, the purified protein was analyzed by SDS
      PAGE electrophoresis and Coomassic brilliant blue R250 stain and only one single
      protein band was seen, Its specificity was demonstrated by Western-blot and
      Immunodot. 49 HBeAb positive sera of hepatitis B patients could be specifically
      detected with the purified HBeAg by ELISA and immunostrip assay, but the latter
      was more sensitive and specific.

PMID- 12526336
TI  - [Serologic testing of hepatitis C virus infection].
AB  - We tested anti-HCV, anti-HCV IgM and HCV-RNA in serum samples from general
      adults, blood donors, acute hepatitis patients and liver cirrhosis patients by
      the methods of ELISA and RT-PCR so as to study the relationship among serum
      markers. Results showed that the detected positive rates of anti-HCV are 3.57%,
      8.58%, 6.25% and 48.38% in normal adults, blood donors, acute hepatitis patients
      and liver cirrhosis patients respectively; agreement rates between anti-HCV and
      HCV RNA are 11.43%, 61.11%, 80.0%, and 73.33% in the four groups of people above;
      agreement rates between anti-HCV IgM and HCV RNA are 75.0%, 90.9% 81.81% and 100%
      in the same groups of people. Authors pointed out that anti-HCV IgM is superior
      to anti-HCV in the aspect of revealing HCV viremia. In comparison with RT-PCR,
      testing anti-HCV IgM is easier and does not need special instruments, so it is
      suitable to develop in the basic hygiene units. Testing anti-HCV IgM instead of
      anti-HCV, the morbidity of post-transfusion hepatitis C can be decreased further.

PMID- 12526337
TI  - [Detection of proviral gene of human immunodeficiency virus type 1 from dried
      blood spots].
AB  - A method for detection of proviral human immunodeficiency virus type 1 DNA
      fragment encoded pol gene in dried blood spots on filter paper by nested primers
      polymerase chain reaction (nPCR) has been developed. The filter paper was pre
      saturated and dried by EDTA proteineas K. About 50 microliters whole blood from
      HIV1 infected individuals was collected and onto the piece of filter paper, and
      the paper was air dried stored sealed in a plastic bag at 4 degrees C or room
      temperature for 1 to 64 weeks. The PCR with outer primers was performed in 0.5%
      ml tube with the piece of filter paper. Following the PCR with the inner primers
      was finished. The results showed that template DNA could detected in piece of
      filter papers which stored at 4 degrees C for 40 weeks as well as stored at room
      temperature for 24 weeks. The results could directly determined by ethidium
      bromide staining of the PCR products when it compared with the PCR products of
      standard positive control and DNA molecular weight marker in electrophoresis
      analysis on agarose gel. The method is rapid, specific, and sensitive and has the
      ability to detect as little as 10 proviral template DNA. The collected samples
      could mail from basic laboratory to center laboratory and the method could be
      applied in confirming and screening of HIV1 infection.

PMID- 12526338
TI  - [Construction of adenovirus type 7(vaccine strain) vector and expression of beta
      galactosidase gene].
AB  - Human adenovirus type 7 DNA was extracted from purified virus cultured in WI-38
      cells. The essential fragment (68-100 mu) of Ad7 DNA was used for constructing a
      non-defective Ad7 vector termed as pAd7 delta E3. The vector was characterized by
      a deletion at the E3 region that contains a multicloning site for the insertion
      of foreign genes. A helper-independent adenovirus type 7-beta-galactosidase
      recombinant was established. The recombinant contains the beta-galactosidase gene
      flanked by CMV early promoter and SV40 poly A signal. The constructed recombinant
      virus showed efficient capacity in expressing the foreign gene, beta
      galactosidase.

PMID- 12526339
TI  - [The target--gene expression of interleukin--12 in HepG2 cells].
AB  - EB virus vector pEBAF, which contains human alpha-fetoprotein gene promoter and
      enhancer was used as expression vector. Two recombinant expression vectors,
      pEBAF/P35 and pEBAF/P40, were constructed and co-transfected into 4 cell lines.
      RT-PCR suggested that both P35 and P40 mRNA are expressed in HepG2 cell secreting
      alpha-fetoprotein, in contrast, neither P35 mRNA nor P40m RNA was expressed in
      non-secreting alpha-fetoprotein cell lines. This proved that the pEBAF may lead
      to target--expression of IL-12 in hepatoma and has tissue specificity and
      exclusiveness for hepatoma. The cotransfected Hyg resistant clone of HepG2 cell
      was selected. Northern blot indicated that the HepG2 cell clone had transcription
      of P35 mRNA and P40 mRNA. Expression of IL-12 in the supernatant of HepG2 cell
      culture had been testified by ELISA and Western blot. IL-12 biological activity
      test indicated that the expressed IL-12 had activity of inducing IFN-gamma
      production. This research laid the foundation to develop an in vivo gene therapy
      strategy pointing to the treatment of hepatocellular carcinoma, with selective
      killing of the tumor cells and no effect on the normal hepatic cells.

PMID- 12526340
TI  - [Cloning and sequencing of fusion protein gene of recombinant GM-HBsAg].
AB  - GM-CSF is an effective adjuvant for immunology, it was used to improve the
      immunological function of antigen and to increase the anti-HBs responses. Through
      using polymerase chain reaction (PCR) technique, we amplified 384 bp and 846 bp
      gene fragments from GM-CSF and HBsAg. The products were extracted and purified; a
      1230 bp gene fragment was obtained by T4 DNA linkage. This amplified product was
      cloned into pUC19 vector. The positive clones were screened and the inserted
      fragment was determined by restriction enzymes. The gene fragment length
      determined is 1230 bp, the sequence analysis showed that the gene fragment is GM
      CSF-HBsAg gene. The successful construction of GM-HBsAg fusion protein gene
      provides basis for research of its biological activity and expression.

PMID- 12526341
TI  - [Effect on HLA-I expression in the presence of antisense oligonucleotides
      complementary to hepatitis B virus x gene].
AB  - In order to investigate inhibition of HLA-I expression by antisense
      oligonucleotides in vitro, three pieces of antisense phosphorothioate
      oligonucleotides (ASODN) complementary to hepatitis B virus (HBV) x gene key
      regions namely, 1510-1530, 1555-1581, 1768-1791 were synthesized. We also
      synthesized a SOND (sense strand) with same sequence of 1510-1530 as control. The
      specificity of inhibitory effect of the ASOND was determined using 2215 cell line
      by detection of HBxAg. In addition, we observed the inhibitory effect of ASODN on
      human HLA-I utilizing 2215 cells, the cells were stained with monoclonal antibody
      against human HLA-I heavy chain molecules, with fluorescenated sheep antimouse
      antibody as the second antibody and then analyzed on a EPICS profile II flow
      cytometer. HLA-I mRNA were assayed by in situ hybridization with a HLA-I heavy
      chain cDNA probe. The results indicated these ASODN could inhibit the expression
      of HBxAg, as well as HLA-I in cell surface. The result of 1 in situ hybridization
      showed that the decreased cell surface expression was correlated with steadily
      decreasing state of mRNA levels. The mechanism of action may be due to the
      inhibition of HBxAg by sequence specific ASODN, then resulting in decreasing of
      its transactivating effect on the HLA-I promoter.

PMID- 12526342
TI  - [The localization of FasL mRNA in liver tissues of chronic hepatitis B].
AB  - To study the expression of FasL mRNA in liver tissues of CHB, we investigated
      FasL mRNA by in situ hybridization in liver tissues from patients with chronic
      hepatitis B. FasL oligonucleotide probes were synthesized and labeled with DIG
      Oligonucleotide 3'-End Labeling Kit. FasL mRNA was found in cytoplasm of liver
      infiltrating mononuclear cells, hepatocytes and some sinus cells. FasL mRNA
      positive hepatocytes were present mainly at the edges of 'piecemeal necrosis(PN)'
      and 'bridging necrosis (BN)'. These results demonstrated that human hepatocytes
      themselves can express FasL in chronic hepatitis B. We deem that FasL-positive
      hepatocytes might express cytotoxic activity and eliminate Fas-positive
      hepatocytes by both 'fratricide' and 'suicide'. These results also emphasize that
      apoptosis caused by CTL through Fas-mediated pathway may play an important role
      in CHB.

PMID- 12526343
TI  - [Hepatitis B virus antigen-induced specific TCR V beta gene subfamily
      amplifications and their diversity].
AB  - The human immune system confronts various antigens, then the recognitive
      structures of T lymphocytes must be diverse. In this study, we analyzed the TCR V
      beta 1-20 gene repertoire by reverse transcription-polymerase chain reaction (RT
      PCR) in peripheral blood lymphocytes (PBLs) from individuals vaccinated with
      recombinant hepatitis B vaccine and PBLs from healthy donors stimulated by
      supernatants of the HepG2 2215 cell line transfected by HBV-DNA. The specific
      amplifications of V beta 6, 14, V beta 6, 15 were observed in PBLs after
      vaccination and stimulation by HepG2 2215 cell line respectively. The results
      suggest that the V beta segments may be the specific recognitive units for these
      antigens and involved in restriction and cytotoxicity.

PMID- 12526344
TI  - [Genetic characterization of an avian influenza A (H5N1) virus isolated from a
      sick goose in China].
AB  - Genetic analysis of viral HA gene showed that there were 22 nucleotide
      differences in HA gene between goose and human H5N1 viruses. The sequence
      analysis of amino acid on viral protein molecules indicated that there were 7 and
      9 position differences between goose and human, chicken H5N1 viruses,
      respectively. All the three viruses share multiple basic amino acids (R-E-R-R-R-K
      K-R) at the cleavage site between HA1 and HA2 domain, that is associated with
      highly pathogenic H5 avian viruses. Except one more glycosylation site located at
      156 position in the chicken strain, there were 7 glycosylation sites at same
      positions in three virus HA protein molecules. The analysis of NA protein
      molecule indicated that the stalk region which extends from the viral membrane up
      to amino acid 85, human and chicken viruses had a 19 amino-acid deletion as
      compared with that of goose virus, while the goose NA gene was closely related to
      A/Parrot/Ulster/73 (H7N1) virus. Therefore, goose H5N1 virus HA and NA genes were
      avian in origin and were different from those of human and chicken H5N1 viruses.
      In our knowledge, this is the first time that the avian H5N1 virus was found
      causing influenza outbreak in goose. Why was A/Goose/Guangdong/2/96(H5N1) virus
      virulent for geese? It might be related to the substitution of amino acid located
      at 138 position near by RBS on HA protein molecule and 19 amino acids insertion
      on NA protein molecule as compared with those of human and chicken H5N1 viruses.

PMID- 12526345
TI  - [Detection of hepatitis C virus-C, E, NS3 and NS4 regions' antigens in
      hepatocellular carcinoma and liver cirrhosis].
AB  - Using 4 McAbs to HCV-C, E, NS3 and NS4 regions' antigens and PcAb to HBsAg, 59
      cases of hepatocellular carcinoma(HCC) and 35 cases of liver cirrhosis(LC) were
      tested by immunohistochemistry technique. Positive reactions for hepatitis C
      virus were mainly present in the cytoplasm of hepatocytes and tumor cells with
      fine granules. The positive rates of HCV were 17.2% in HCC(29 cases) of Beijing,
      26.7% in HCC(30 cases) of Shenyang and 14.3% in LC(35 cases) of Shenyang. C
      region's McAb had the highest positive rate of detection, which suggested that C
      region's protein had a high level expression. The positive rates of hepatitis B
      virus surface antigen were 63.0% in HCC(29 cases) of Beijing, 73.3% in HCC(30
      cases) of Shenyang and 54.3% in LC(35 cases) of Shenyang, all of which were
      higher than their positive rate for HCV detected. In HCC and LC, HBV and HCV
      inclined to suppress the opposite side.

PMID- 12526346
TI  - [An analysis of hepatitis G virus infection status in various cases of hepatitis
      in Guangdong area].
AB  - To understand hepatitis G virus(HGV) infection status in different clinical types
      of hepatitis, 721 cases with hepatitis were analyzed in this article. PT-PCR
      technique was applied to amplify HGV gene, and heat denaturation method was used
      to extract HCV-RNA from sera. After turning to cDNA by reverse transcription(PT),
      a nested amplification was conducted and a 238 bp specific fragment was obtained.
      In this way, serum specimens of 721 cases with hepatitis, were tested including
      587 hospitalized cases. 80 cases were found to be HGV RNA positive, of which
      positive rate of patients with non A-E hepatitis was high, HCV and HBV + HCV came
      the second, chronic severe hepatitis and liver cirrhosis (LC) was the lower.
      Results of research showed that HGV infection is prevalent to a certain degree
      among patients with viral hepatitis in Guangdong area.

PMID- 12526347
TI  - [The clinical and enzymatic changes in patients with viral hepatitis G
      infection].
AB  - For the purpose of making sure the clinical significance of hepatitis G virus, RT
      nested PCR was applied to detect HGV RNA in 165 hepatitis patients, which
      included 24 acute hepatitis, 78 chronic hepatitis, 18 hepatitic cirrhosis, 4
      hepatocellularcarcinom and 41 HBV and HCV carriers. The results showed that the
      infection of HGV existed in all kinds of hepatitis patients. Among the acute
      hepatitis 12.5% (3/24) was HGV RNA positive. 19 (24.4%) cases were HGV RNA
      positive in chronic hepatitis, among which 4 cases were simply HGV RNA positive
      (5.13%). The serum ALT level in 3 cases of simple acute HGV patients was between
      488 +/- 65 U/L, the value of AST between 452 +/- 71 U/L, the TBiL at about 77.1
      +/- 14.3 mumol/L. All these showed that only HGV infection could lead to acute
      hepatitis. The rising enzyme dropped to normal about a month later in acute
      hepatitis while HGV RNA would remain. The problem whether HGV infection is caused
      by simple acute and chronic hepatitis infection is under investigation.

PMID- 12526348
TI  - [Investigation of HGV infection in various populations in Guangxi].
AB  - In order to understand the situation of HGV infection in various populations in
      Liuzhou prefecture of Guangxi, Zhuangzu Autonomous Region, and also to compare
      the HGV, HBV, HCV infections between intravenous drug abusers and healthy persons
      (those for physical examination, the same below), the anti-HGV, -HCV and HBVM
      (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) were detected by ELA and, besides, tested
      further the 20 anti-HGV seropositive cases for HGV-RNA by RT-nPCR. The results
      showed that in the populations tested, the HGV seropositive rate was 9.8%
      (106/1079), separately they were 23.8% (5/21), 21.1% (23/109), 12.5% (6/48),
      12.0% (6/50), 12.0% (20/166), 9.3% (3/32), 8.2% (34/413), 4.3% (6/140), and 3.0%
      (3/100) in liver cirrhosis, intravenous drug abusers, repeated blood and blood
      products transfused patients, hepatocellularcarcinoma patients, viral hepatitis,
      haemodialysis patients, healthy persons, paid blood donors and healthy pregnant
      women respectively. In intravenous drug abusers, the HGV, HBV, HCV infection rate
      were 21.2% (23/109), 75.3% (82/109) and 7.3% (8/109) respectively, while they
      were 8.2% (9/109), 20.1% (22/109), and 1.8% (2/109) in healthy persons
      respectively. These data showed that Liuzhou prefecture of Guangxi was HGV high
      epidemic area, HGV infection rate was higher in populations of intravenous drug
      abusers, viral hepatitis, liver cirrhosis and repeatedly blood and blood products
      transfused patients, even in pregnant women the HGV infection also occurred.
      There was a significant difference of HGV, HBV, HCV infection rates between
      intravenous drug abusers and healthy persons (P < 0.005).

PMID- 12526349
TI  - [Detection of GBV-C/HGV infection in patients with liver diseases].
AB  - The aim of this article is to study the prevalence of GBV-C/HGV in patients with
      liver diseases and the clinical features in patients with (GBV-C/HGV infection.
      The serum samples were obtained from 169 patients with liver diseases in You An
      Hospital). Serum GBV-C/HGV RNA was detected by reverse transcription nested
      polymerase chain reaction (RT-nPCR) using two primer pairs of 5' untranslated
      region (5' UTR) of HGV. Serum anti-HGV was detected by ELISA simultaneously. The
      partial GBV-C/HGV genome isolated from one patient was cloned into T vectors and
      sequenced by dideoxy-mediated chain termination methods. Among 169 patients with
      various liver diseases, the GBV-C/HGV RNA positive rate was 9.5% (16/169),
      including 11.1% (1/9) of AHA, 4.1% (3/73) of CHB, 16.2% (6/37) of CHC, 13.3%
      (2/15) of AH(nonA-E) 12.5% (1/8) of CH(nonA-E) 15.4% (2/13) of LC and 33.3% (1/3)
      of SH cases. Of 29 patients having a history of surgical operation and
      transfusion, 9(31.0%) was positive for GBV-C/HGV RNA, which was remarkably higher
      than those cases without surgical operation and transfusion. The sequence
      analysis showed that there was 89.14%-98.91% nucleotide identity between our
      isolate and published GBV-C/HGV isolates. The results also suggested that
      infection rate of GBV-C/HGV was around 9.5% in patients from Beijing region,
      patients with GBV-C/HGV infection might show various clinical features and GBV
      C/HGV might not be the major cause of hepatitis nonA-E.

PMID- 12526350
TI  - [Sequencing and analysis of the NS5 region of HGV/GBV-C gene].
AB  - To study the genomic organization of non structural region 5 of HGV in China, 186
      nucleotides of NS5 region of HGV were amplified, cloned and sequenced. The data
      were analyzed with computer programs. The results indicated that the gene
      sequence homology between 2 HGV isolates in this study was 95.2%. The comparison
      of these 2 isolates and 3 foreign isolates reported previously showed that the
      sequence homology was in the range of 84.4% to 92.4%, and was obvious by
      divergent from the foreign isolates. The results make us consider that HGV may
      have different genotypes, after a further inspection into the gene sequence of
      each region of HGV. The 2 isolates were from the sera collected in 1984,
      therefore the existence of HGV infection in Harbin was retrospectively traced to
      1980s.

PMID- 12526351
TI  - [Investigation of hepatitis G virus and human immunodeficiency virus infections
      in 831 healthy youths].
AB  - Antibodies to hepatitis G virus(HGV) and human immunodeficiency virus(HIV) by EIA
      were investigated in 831 healthy youths from 6 provinces. The results showed that
      the anti-HGV IgG positive rate was 2.53% (21/831). In 21 anti-HGV IgG positive
      sera, HGV RNA was detected in 8 sera by reverse transcription polymerase chain
      reaction(RT-PCR). The anti-HIV was negative in 827 sera. The data suggest that
      HGV infection actually exist in healthy youths.

PMID- 12526352
TI  - [Soluble expression and identification of expressed single chain antibody
      fragment 3D3 against dengue virus type 3].
AB  - Hybridoma secreting 3D3 monoclonal antibody against dengue virus type 3 was used.
      The isolated mRNA was reverse-transcribed into cDNA for amplifying the heavy and
      light chain variable domains genes. The amplified light and heavy chain variable
      domains' genes were connected by flexible linker to from a single chain fragment
      (ScFv) gene of 750 bp, which was cloned into phage pCANTAB5E vector using the
      recombination phage antibody system. pCANTAB5E vector transformed E coli HB2151.
      Soluble single chain antibody fragment was expressed both in the bacterial
      supernatant and cell periplasm under the induction of IPTG. The expressed single
      chain antibody fragment has a molecular weight of about 28 kD detected by SDS
      PAGE and can react with dengue virus type 3 by immunofluorescence test.

PMID- 12526353
TI  - [Expression of Epstein-Barr virus membrane antigen in CHO cell].
AB  - A recombinant plasmid, pCMV/MA, was generated by isolating the Epstein-Barr
      Virus(EBV) membrane antigen(MA) gene with anchor sequence removed from pSV40/MA
      and cloning it into pcDNA3, with MA gene and Neomycin gene under the control of
      CMV promoter and SV40 promoter respectively. CHO cells were transfected with
      pCMV/MA using liposome and then grown in DMEM medium in the presence of G418. Two
      clones highly expressing MA were obtained. EBV-MA was purified from the medium of
      CHO cells by ammonium sulfate precipitation. Western-blot showed that the
      molecular weight of proteins expressed were about 340 kD and 220 kD. It could
      specifically react with anti-MA monoclonal antibody in indirect immunofluorescent
      and immunodot assay. The yield of MA was estimated to be 1.9 micrograms/ml per
      day by SDS-PAGE scanning and Lowry methods. The optimal culture condition of the
      CHO cells was to use medium supplemented with 10% serum until 80% cell
      confluence, then with 2%-5% serum and collected medium continually. The genetic
      stability of the cells was confirmed by freeze--revival and culture without G418.
      The purified MA was used to immunize mice and the geometric mean titer of the
      specific antibody was 1:180, while the positive rate of antibody was 100%.

PMID- 12526354
TI  - [Establishment and primary study of an assay for the detection of EB virus
      specific cytotoxic T lymphocytes].
AB  - In our study, a non-radioactive cytotoxicity assay by using a Balb/C (H-2d) mice,
      P815(H-2d) cells and lactate dehydrogenase (LDH) system was established, in order
      to detect EB virus specific cytotoxic T lymphocytes(CTLs). In this study, we
      detected both the changes of primary CTLs and secondary stimulated CTLs. Spleen
      CTL activity assay showed that the levels of primary and secondary CTLs in
      recombinant EBV-LMP1 vaccinia virus group were more higher than that in control
      group, at the same time, obvious enhancement of EBV-LMP1 specific CTL activity
      was observed in experimental group immunized by Baculovirus system expressing EBV
      LMP1 protein when compared with the normal mice group. This work proved that the
      LDH assay can be used to detect cytotoxic T lymphocytes.

PMID- 12526355
TI  - [Antiviral activity of antisense oligonucleotides to human cytomegalovirus].
AB  - Human cytomegalovirus(HCMV) is one of the important pathogens to human being. At
      present there is no specific antiviral drugs. In order to find an effective
      antisense phosphorothioate deoxyoligonucleotide(ASON) against--HCMV, the
      antiviral activity was observed in this study. Three ASON complementary to UL36
      gene were synthesized according to immediate early gene sequence of HCMV, and the
      antiviral activity was evaluated in vitro using human embryonic lung cells as
      targeted cells of virus infections. The result showed that ASON targeting to
      splice donor had fairly strong antiviral activity. The specific ASON has sure
      antiviral activity. As a new means, it may be used to prevent and treat human CMV
      infections.

PMID- 12526356
TI  - [The relation of neonatal hyaline membrane disease and congenital human
      cytomegalovirus infection].
AB  - To study the relation of neonatal hyaline membrane disease (HMD) and congenital
      human cytomegalovirus (HCMV) infection, two pairs of primers were synthesized
      according to the sequence of HCMV conserved region of the immediate--early(IE)
      gene. The nested polymerase chain reaction (nested-PCR) was used for the
      detection of HCMV-DNA of the paraffin-embedded lung tissues from neonatal HMD and
      non-neonatal HMD. 11 of 30 neonatal HMD patients were positive, the positive rate
      was 36.7%. Specimens of non-neonatal HMD patients were all negative. The
      difference between the two groups was significant (chi 2 = 5.05, P < 0.025).
      There is close relationship between neonatal HMD and congenital HCMV infection.

PMID- 12526357
TI  - [Study on the contents of HBV DNA in sera of patients with hepatic diseases by
      QPCR technique].
AB  - In order to test the content of serum HBV DNA for evaluating the effectiveness of
      clinical antiviral treatment and the relation of serum HBV DNA level to state of
      illness and prognosis, a QPCR method of energy transfer in amplification by semi
      nested fluorescein labeled primer was established. Serum HBV DNA contents of 63
      cases of hepatic diseases with abnormal liver function were detected by QPCR, PCR
      and ELISA. The positive detectable rate of the three methods were compared. The
      results showed that the positive detectable rate of QPCR was 82.54%, PCR 71.43%
      and ELISA 63.50%. The detectable rate of QPCR was compared with PCR, and
      uniformity rate of the both methods was 88.89%, P < 0.05; the positive results of
      QPCR were compared with ELISA, and their uniformity rate was 80.95%, P < 0.05;
      when serum average content (mean +/- s) of HBV DNA by QPCR method was compared
      with serum average titer of HBV by ELISA method, serum HBV-DNA average content of
      the group in which both QPCR and ELISA were positive was much higher than that of
      the group of QPCR(+) and ELISA(-), P < 0.05; serum QPCR-HBV-DNA of 30 cases of
      healthy persons were all negative. The results indicated that QPCR method is of
      highest positive detectable rate and more specific in detecting serum HBV DNA and
      had no nonspecific amplifying reaction. It has the superiority of detecting low
      level serum HBV DNA.

PMID- 12526359
TI  - [A 5-year follow-up study of antiviral effect of interferon in patients with
      chronic hepatitis C].
AB  - In order to discuss the anti-viral effects of IFN alpha-2a and IFN alpha-2b on
      chronic hepatitis C in a short and long period of time after treatment, 70 cases
      of chronic hepatitis C treated with IFN alpha-2a, 46 cases with IFN alpha-2b and
      28 cases as controls had been investigated in this study. The follow-up time
      began from half to 5 years. The serum negative conversion rate of HCV RNA and the
      normalization of serum alanine transaminase(ALT) were detected at the end of
      treatment and up to 5 years after therapy. The negative seroconversion rate of
      HCV RNA and the serum ALT normalization were 67.14% and 70.00% respectively in
      IFN alpha-2a group and 69.56%, 71.71% respectively in IFN alpha-2b group at the
      end of the treatment. After 5-year follow-up, the above two Indexes were 35.71%,
      47.14% respectively in IFN alpha-2a group, and 39.13%, 52.17% respectively in IFN
      alpha-2b group. The effectiveness in treated patients was higher than that of
      controls (P < 0.01 and P < 0.05). Recombinant IFN alpha-2a and IFN alpha-2b are
      effective medicines for HCV infection. And interferon therapy had a high short
      term complete response but a low long-term complete response in the treatment of
      chronic hepatitis C. HCV genotype seems to be an important factor in determining
      the response rate of IFN treatment in patients with chronic hepatitis C.

PMID- 12526358
TI  - [Therapeutic effect of recombinant interferon alpha-2b on hemorrhagic fever with
      renal syndrome].
AB  - To study the therapeutic effect of recombinant interferon alpha-2b(rIFN alpha-2b)
      on cases of hemorrhagic fever with renal syndrome(HFRS) in early stage, 146 cases
      of HFRS in feverish stage and within five days of onset were randomly divided
      into two groups: the treatment and the control, each group included 73 cases. The
      control group was given the traditional combined therapy with a predominance of
      balanced solution, the treatment group was given rIFN alpha-2b 1 x 10(6)U per
      day, i.m., for three days. The treatment group showed much better effects in
      improving the viremia, the clinical conditions, skipping phases, restoring kidney
      function and platelet account, decreasing complications than the control group (P
      < 0.05). All the patients of the treatment group recovered, and four patients of
      the control group died, accounting for 5.47%. No side-effect resulting from rIFN
      alpha-2b was found. Administration of rIFN alpha-2b to patients with HFRS within
      five days of onset could lighten the organ lesions, shorten the course of disease
      and raise the curative rate.

PMID- 12526360
TI  - [The coinfection of hepatitis C virus with hepatitis G virus and its reaction to
      interferon treatment].
AB  - HGV RNA was detected in 60 cases of hepatitis C patients and its positive rate
      was 23.3%, also the HGV infection was more frequent in chronic hepatitis C
      patients than in acute hepatitis C, and was only detected in hepatitis C patients
      who experienced transfusion of blood or blood products. These results indicated
      that transfusion was the main transmission route for HGV infection. HGV infection
      could shorten the incubation period of post-transfusion hepatitis C, but it would
      not worsen the status of the disease. The coinfection of HCV and HGV did not
      interfere the effect of interferon treatment on hepatitis C patients either in
      normalization of ALT or the elimination of HCV.

PMID- 12526361
TI  - [Progress in the study of molecular biology of thrombopoietin].

PMID- 12526362
TI  - [Advances in the study of influence vaccines].

PMID- 12526363
TI  - One-dimensional antiferromagnetic chain in [Ni(dmit)2]- salts of [K+ or Rb+(4,13
      diaza-18-crown-6)] supramolecular cation.

PMID- 12526365
TI  - Structural, spectroscopic, and electrochemical studies of binuclear manganese(II)
      complexes of bis(pentadentate) ligands derived from bis(1,4,7-triazacyclononane)
      macrocycles.
AB  - Structural, electrochemical, ESR, and H2O2 reactivity studies are reported for
      [Mn(dmptacn)Cl]ClO4 (1, dmptacn = 1,4-bis(2-pyridylmethyl)-1,4,7
      triazacyclononane) and binuclear complexes of bis(pentadentate) ligands,
      generated by attaching 2-pyridylmethyl arms to each secondary nitrogen in
      bis(1,4,7-triazacyclononane) macrocycles and linked by ethyl (tmpdtne,
      [Mn2(tmpdtne)Cl2](ClO4)2.2DMF, 2), propyl (tmpdtnp,
      [Mn2(tmpdtnp)Cl2](ClO4)2.3H2O, 3), butyl (tmpdtnb,
      [Mn2(tmpdtnb)Cl2](ClO4)2.DMF.2H2O, 4), m-xylyl (tmpdtn-m-X, [Mn2(tmpdtn-m-X)
      Cl2](ClO4)2, 5) and 2-propanol (tmpdtnp-OH, [Mn2(tmpdtnp-OH)Cl2](ClO4)2, 6)
      groups. 1 crystallizes in the orthorhombic space group P2(1)2(1)2(1) (No. 19)
      with a = 7.959(7) A, b = 12.30(1) A, and c = 21.72(2) A; 2, in the monoclinic
      space group P2(1)/c (No. 14) with a = 11.455(4) A, b = 15.037(6) A, c = 15.887(4)
      A, and beta = 96.48(2) degrees; 3, in the monoclinic space group P2(1)/c (No. 14)
      with a = 13.334(2) A, b = 19.926(2) A, c = 18.799(1) A, and beta = 104.328(8)
      degrees; and [Mn2(tmpdtnb)Cl2](ClO4)2.4DMF.3H2O (4'), in the monoclinic space
      group P2(1)/n (No. 14) with a = 13.361(3) A, b = 16.807(5) A, c = 14.339(4) A,
      and beta = 111.14(2) degrees. Significant distortion of the Mn(II) geometry is
      evident from the angle subtended by the five-membered chelate (ca. 75 degrees)
      and the angles spanned by trans donor atoms (< 160 degrees). The Mn geometry is
      intermediate between octahedral and trigonal prismatic, and for complexes 2-4,
      there is a systematic increase in M...M distance with the length of the alkyl
      chain. Cyclic and square-wave voltammetric studies indicate that 1 undergoes a 1e
      oxidation from Mn(II) to Mn(III) followed by a further oxidation to MnIV at a
      significantly more positive potential. The binuclear Mn(II) complexes 2-5 are
      oxidized to the Mn(III) state in two unresolved 1e- processes [MnII2-->MnIIMnIII-
      >MnIII2] and then to the MnIV state [MnIII2-->MnIIIMnIV-->MnIV2]. For 2, the
      second oxidation process was partially resolved into two 1e- oxidation processes
      under the conditions of square-wave voltammetry. In the case of 6, initial
      oxidation to the MnIII2 state occurs in two overlapping 1e- processes as was
      found for 2-5, but this complex then undergoes two further clearly separated 1e-
      oxidation processes to the MnIIIMnIV state at +0.89 V and the MnIV2 state at
      +1.33 V (vs Fc/Fc+). This behavior is attributed to formation of an alkoxo
      bridged complex. Complexes 1-6 were found to catalyze the disproportionation of
      H2O2. Addition of H2O2 to 2 generated an oxo-bridged mixed-valent MnIIIMnIV
      intermediate with a characteristic 16-line ESR signal.

PMID- 12526364
TI  - Magnetic interactions in the high-spin iron(III) oxooctaethylchlorinato
      derivative [Fe(oxoOEC)(Cl)] and its pi-cation radical [Fe(oxoOEC.)(Cl)]SbCl6.
AB  - The preparation and characterization of the beta-oxochlorin derivative
      [3,3,7,8,12,13,17,18-octaethyl-(3H)-porphin-2-onato(2-)]iron(III) chloride,
      [Fe(oxoOEC)(Cl)], and its pi-cation radical derivative [Fe(oxoOEC.)(Cl)]SbCl6 is
      described. Both compounds have been characterized by single-crystal X-ray
      structure determinations, IR, UV/vis/near-IR, and Mossbauer spectroscopies, and
      temperature-dependent magnetic susceptibility measurements. The macrocycles of
      [Fe(oxoOEC)(Cl)] and [Fe(oxoOEC.)(Cl)]SbCl6 are both saddled, and
      [Fe(oxoOEC.)(Cl)]-SbCl6 is slightly ruffled as well. [Fe(oxoOEC)(Cl)] shows a
      laterally shifted dimeric unit in the solid state, with a mean plane separation
      of 3.39 A and a lateral shift of 7.39 A. Crystal data for [Fe(oxoOEC)(Cl)]:
      triclinic, space group P1, Z = 2, a = 9.174(2) A, b = 13.522(3) A, c = 14.838(3)
      A, alpha = 95.79(3) degrees, beta = 101.46(2) degrees, gamma = 104.84(3) degrees.
      Upon oxidation, the inter-ring geometric parameters increase; the mean plane
      separation and the lateral shift of the dimeric unit of [Fe(oxoOEC.)(Cl)]SbCl6
      are 4.82 and 8.79 A, respectively. Crystal data for [Fe(oxoOEC.)(Cl)]SbCl6:
      monoclinic, space group Cc, Z = 4, a = 19.8419(13) A, b = 10.027(2) A, c =
      22.417(4) A, beta = 96.13(2) degrees. A broad near-IR absorption band appears at
      1415 nm for the pi-cation radical, [Fe(oxoOEC.)(Cl)]SbCl6. Zero-field Mossbauer
      measurements at 4.2 K for both [Fe(oxoOEC)(Cl)] and [Fe(oxoOEC.)(Cl)]SbCl6
      confirmed that the oxidation state of the iron atom did not change upon chemical
      oxidation. Solid-state magnetic susceptibility measurements for
      [Fe(oxoOEC.)(Cl)]SbCl6 resulted in a large temperature dependence of the magnetic
      moment that can best be fit with a model that includes a zero-field splitting
      parameter of D = 6 cm-1, antiferromagnetic intermolecular iron-iron coupling
      (2JFe-Fe = -0.14 cm-1), antiferromagnetic intramolecular iron-radical coupling
      (2JFe-r = -76 cm-1), and antiferromagnetic radical-radical coupling (2Jr-r = -13
      cm-1).

PMID- 12526366
TI  - Step-scan FTIR time-resolved spectroscopy study of excited-state dipole
      orientation in soluble metallopolymers.
AB  - Step-scan FTIR time-resolved spectroscopy (S2FTIR TRS) in acetonitrile-d3 has
      been used to probe the acceptor ligand in metal-to-ligand charge transfer (MLCT)
      excited states of amide-substituted polypyridyl complexes of RuII and in
      analogues appended to polystyrene. On the basis of ground-to-excited state shifts
      in v(C = O) of -31 cm-1 for the amide group in [RuII(bpy)2(bpyCONHEt')]2+
      (bpyCONHEt' = 4'-methyl-2,2'-bipyridine-4-carboxamide-Et'; Et' = -CH2CH2BzCH2CH3)
      (1) and in the derivatized polystyrene abbreviated [PS-[CH2-CH2NHCObpy
      RuII(bpy)2]20]40+ (3), the excited-state dipole is directed toward the amide
      containing pyridyl group in the polymer side chain. Smaller shifts in v(C = O) of
      -17 cm-1 in [RuII(4,4'-(CONEt2)2bpy)2-(bpyCONHEt')]2+ (2) and in the derivatized
      polystyrene abbreviated [PS-[CH2CH2NHCObpy-RuII(4,4'-(CONEt2)2bpy)2]20]40+ (4)
      indicate that the excited-state dipole is directed toward one of the diamide bpy
      ligands. The nearly identical results for 1 and 3 and for 2 and 4 show that the
      molecular and electronic structures of the monomer excited states are largely
      retained in the polymer samples. These conclusions about dipole orientation in
      the polymers are potentially of importance in understanding intrastrand energy
      transfer dynamics. The excited-state dipole in 3 is oriented in the direction of
      the covalent link to the polymer backbone, and toward nearest neighbors. In 4, it
      is oriented away from the backbone.

PMID- 12526367
TI  - Catalysis of the silica sol-gel process by divalent transition metal
      bis(acetylacetonate) complexes.
AB  - Transition metal bis(acetylacetonate) complexes of Co(II), Ni(II), Cu(II), and
      Zn(II) have been found to be active catalysts for the sol-gel process. The
      catalytic activity of these complexes decreases in going from Co(II) to Zn(II)
      and is highest for the acetylacetonate ligand system. 29Si NMR studies show that
      the complexes act primarily as condensation catalysts and are, in that regard,
      similar to Bronsted bases such as hydroxide. Mechanistically, however, they
      appear to differ significantly from hydroxide in how they induce condensation.
      This is revealed in the catalyst concentration dependence, which is 1/2 order for
      the metal complexes and 1st order in hydroxide. Differences are also apparent in
      the thermochemical parameters that indicate that the metal complexes act to
      increase the entropy of the transition state leading to condensation. The
      catalytic activity is proportional to the degree of ligand dissociation of the
      metal complex, and experiments suggest that the active catalytic species is
      specifically the first dissociation product, MII(acac)+.

PMID- 12526368
TI  - Structural correlations and conformational preference in edge-sharing binuclear
      d8 complexes with XR2 bridges. A theoretical study.
AB  - The binuclear complexes of d8 transition metal ions of the type [M2(mu-XR2)2L4]
      (where M = RhI, IrI, NiII, PdII, PtII, or AuIII; X = S, N, P, or As) appear in a
      variety of molecular conformations in which the coordination planes around the
      two metal atoms are sometimes coplanar, sometimes bent. For the bent compounds
      with asymmetric bridges, XR1R2, the substituents adopt different orientations
      relative to the metal framework and to each other. Ab initio theoretical studies
      on the different conformers of 30 representative complexes, complemented with a
      structural database analysis, have allowed the establishment of structural
      correlations in this family of compounds. The conformational choice results from
      a delicate balance of different interactions which are qualitatively analyzed,
      such as the changes in bond angles around the bridging atoms, the existence of
      weak metal...metal bonding in the bent structures, and steric interactions
      involving the terminal ligands and the substituents at the bridging atoms.

PMID- 12526369
TI  - Evolution of the Jahn-Teller distortion of MnO6 octahedra in RMnO3 perovskites (R
      = Pr, Nd, Dy, Tb, Ho, Er, Y): a neutron diffraction study.
AB  - Stoichiometric RMnO3 perovskites have been prepared in the widest range of R3+
      ionic sizes, from PrMnO3 to ErMnO3. Soft-chemistry procedures have been employed;
      inert-atmosphere annealings were required to synthesize the materials with more
      basic R cations (R = Pr, Nd), in order to minimize the unwanted presence of Mn4+.
      On the contrary, annealings in O2 flow were necessary to stabilize the perovskite
      phases for the last terms of the series, HoMnO3, ErMnO3, and YMnO3, thus avoiding
      or minimizing the formation of competitive hexagonal phases with the same
      stoichiometry. The samples have been investigated at room temperature by high
      resolution neutron powder diffraction to follow the evolution of the crystal
      structures along the series. The results are compared with reported data for
      LaMnO3. The distortion of the orthorhombic perovskite (space group Pbnm),
      characterized by the tilting angle of the MnO6 octahedra, progressively increases
      from Pr to Er due to simple steric factors. Additionally, all of the perovskites
      show a distortion of the MnO6 octahedra due to the orbital ordering
      characteristic of the Jahn-Teller effect of Mn3+ cations. The degree of orbital
      ordering slightly increases from La to Tb and then remains almost unchanged for
      the last terms of the series. The stability of the crystal structure is also
      discussed in light of bond-valence arguments.

PMID- 12526370
TI  - Synthesis of MII[N(SiMe3)2][Me3SiNC(tBu)NSiMe3] (M = Sn, Ge) from amidinate
      precursors: active catalysts for phenyl isocyanate cyclization.
AB  - Mixed amidinato amido complexes [Me3SiNC(tBu)NSiMe3]M[N(SiMe3)2] (M = Sn 2, Ge 3)
      were prepared by the reaction of [Me3SiNC(tBu)NSiMe3]Li (1a) with SnCl2 and
      GeCl2(dioxane) in ether. The N(SiMe3)2 ligand in these compounds is derived from
      the rearrangement of the [Me3SiNC(tBu)NSiMe3]- anion with extrusion of tBuCN. The
      susceptibility of [Me3SiNC(tBu)NSiMe3]- to rearrangement appears to be dependent
      on reaction solvent and on the coordinated metal center. Single-crystal X-ray
      diffraction studies of 2 and 3 are presented. Replacement of Me for tBu in the
      ligand allowed [Me3SiNC(Me)NSiMe3]2SnII (4) to be isolated, and an X-ray
      structure of this compound is reported. The isolation of 4 indicates that steric
      factors also play a role in the stability of [Me3SiNC(tBu)NSiMe3]-. Compounds 2
      and 3 are outstanding catalysts for the cyclotrimerization of phenyl isocyanates
      to perhydro-1,3,5-triazine-2,4,6-triones (isocyanurates) at room temperature. In
      contrast, complex 4 catalytically reacts with phenyl isocyanate to produce
      isocyanate dimer and trimer in a 52:35 ratio.

PMID- 12526371
TI  - Molecular and electronic structure of nitridocyanometalates of chromium(V) and
      manganese(V): a combined experimental and DFT study.
AB  - The six-coordinate complexes [M(N)(CN)5]3- (M = Cr, Mn) have been isolated as
      salts of robust rhodium amine complexes. [Rh(en)3][Mn(N)(CN)5].H2O (1) and
      [Rh(tn)3] [Cr(N)(CN)5].2H2O (2) have been characterized by single-crystal X-ray
      crystallography: 1 crystallizes in the hexagonal space group P6(3) with a = b =
      15.810(2) A, c = 13.844(3) A, V = 2996.8(8) A3, and Z = 6; 2 crystallizes in the
      orthorhombic space group Pbcn with a = 9.723(1) A, b = 14.564(2) A, c = 31.498(4)
      A, V = 4460.3(8) A3, and Z = 8. In 1, all the anions are oriented with their Mn
      identical to N directions almost coparallel to the crystallographic 3-fold axis.
      Polarized single-crystal UV-vis spectroscopy of 1 confirms the validity of the
      Jorgensen-Ballhausen-Gray d-orbital splitting scheme with the lowest energy
      transition being dxy-->[dyz,dzx]. Single-crystal EPR spectroscopy of
      [Cr(N)(CN)5]3- diluted into 1 shows the hyperfine (53Cr) and super-hyperfine
      (14N) tensors to be quite anisotropic with different major axes. For the
      hyperfine interaction we observe A Parallel > A Perpendicular, whereas, for the
      super-hyperfine interaction to the terminal nitrido ligand, the reverse ordering
      is found: A Perpendicular > A Parallel. The complexes [M(N)(CN)5]3-, trans
      [M(N)(CN)4(py)]2-, and [M(N)(CN)4]2- (M = Cr, Mn) were investigated by DFT
      methods. Good reproduction of the molecular structures, vibrational, and UV-vis
      spectra was obtained. However, pronounced differences between local density and
      gradient corrected functionals were observed in the description of the weak
      bonding to the ligands trans to the nitrido ligand. For the five-coordinate
      [M(N)(CN)4]2- complexes the LUMO is predicted to be a strongly admixed dz2(M)
      pz(M) hybrid.

PMID- 12526372
TI  - Organotin derivatives of alpha-[XIIIW9O33]9- (X = As, Sb) heteropolytungstates.
      Solution- and solid-state characterization of [[C6H5Sn)2O]2H(alpha-AsW9O33)2]9-
      and [(C6H5Sn)3Na3(alpha-SbW9O33)2]6-.
AB  - The tris(phenyltin)-substituted tungstoantimonate(III) Cs6[(PhSn)3Na3(alpha
      SbW9O33)2].20H2O (1) and the tetrakis-(phenyltin)-substituted
      tungstoarsenate(III) Na9[[(PhSn)2O]2H(alpha-AsW9O33)2].20H2O (2) have been
      prepared by reaction of phenyltin trichloride with Na9[alpha-SbW9O33].19.5H2O and
      Na9[alpha-AsW9O33].19.5H2O, respectively, in aqueous solution. The products were
      characterized by elemental analysis, X-ray crystallography, multinuclear NMR, and
      infrared spectroscopy. Crystals of 1 are monoclinic, space group P2(1)/n, with a
      = 13.7952(1) A, b = 22.3133(2) A, c = 34.4493(2) A, beta = 90.933(1) degrees, and
      Z = 4. Anion 1 has nominal D3h symmetry and contains three PhSn3+ groups and
      three sodium ions sandwiched between [alpha-SbW9O33]9- units. Crystals of 2 are
      triclinic, space group P1, with a = 15.272(6) A, b = 15.303(6) A, c = 16.760(7)
      A, alpha = 93.59(3) degrees, beta = 106.187(19) degrees, gamma = 112.23(3)
      degrees, and Z = 1. Anion 2 has nominal C2h symmetry and contains four PhSn3+
      groups sandwiched between two [alpha-AsW9O33]9- units.

PMID- 12526373
TI  - Mechanism of the S-->N isomerization and aquation of the thiocyanato pentaammine
      cobalt(III) ion.
AB  - All of the stationary points on the potential energy surface of the S-->N
      isomerization and aquation of the Co(NH3)5SCN2+ ion have been investigated with
      ab initio quantum chemical methods. Also the corresponding anations of the
      Co(NH3)5OH2(3+) ion by the N and S ends of SCN- and the substitution of
      thiocyanate via the D mechanism have been studied. All calculations have been
      performed by taking into account hydration. The most favorable reaction of
      Co(NH3)5SCN2+ is the isomerization. It is concerted, follows the I or Id
      mechanism, depending on the applied criteria, and proceeds via a T-shaped
      transition state. The aquations of Co(NH3)5SCN2+ and Co-(NH3)5NCS2+ and the
      corresponding inverse reactions, the anations, all proceed via the Id mechanism.
      The activation energies, calculated for the isomerization and aquation, agree
      with experiment, and so does the difference of the activation energies for the
      anations by the two donors of SCN-. This energy difference reflects the disparate
      nucleophilicities of the N and S ends of SCN- and shows that bond making in the
      transition state is significant for the Id mechanism. Isomerization and aquation
      are two parallel reactions which proceed via two disparate transition states. The
      computed activation energy for the SCN- substitution via the D mechanism is the
      highest, and therefore, this pathway is unlikely to operate for the isomerization
      and aquation of Co(NH3)5SCN2+. The S-->N isomerization and the SCN- substitution
      via the D mechanism were furthermore computed for the free ions in the gas phase:
      the isomerization would require a higher activation energy and follow the Ia
      mechanism. The activation energy for the SCN- substitution via the D mechanism
      would be very high, because of the large electrostatic work which is required for
      the removal of an anion from a (formally) 3+ charged cation.

PMID- 12526374
TI  - Metal-metal interactions in weakly coupled mixed-valence E- and Z
      diferrocenylethylene complexes.
AB  - To study metal-to-metal interactions in mixed-valence states of two weakly
      coupling ferrocenyl groups assembled in E or Z conformation on an ethylenic
      double bond, E-1,2-dimethyldiferrocenylethylene (1), Z-1,2-dimethyldi
      ferrocenylethylene (2), and 1,2-diferrocenylcyclohexene (3) were synthesized and
      structurally characterized. Crystals of 1 are triclinic, P1, with a = 7.494(9) A,
      b = 10.801(3) A, c = 11.971(2) A, alpha = 102.17(2) degrees, beta = 106.12(9)
      degrees, gamma = 90.42(2) degrees, V = 907.8 A3, and Z = 2. Crystals of 2 are
      monoclinic, P2(1)/c, with a = 13.601(8) A, b = 11.104(4) A, c = 13.732(1) A, beta
      = 114.26(7) degrees, V = 1890.8(3) A3, and Z = 4. Crystals of 3 are orthorhombic,
      P2(1)2(1)2(1), with a = 5.766(2) A, b = 13.090(1) A, c = 26.695(2) A, V =
      2014.9(3) A3, and Z = 4. Intervalence transition spectra (IT) and electrochemical
      data have been determined and compared with those of diferrocenyl-benzene (para,
      ortho, and meta). The comproportionation constants in nitrobenzene at 25 degrees
      C were found to be 490 and 813 for 1 and 3, respectively. That of 2 was not
      measured because of the fact that 2+ isomerizes rapidly in all solvents tested,
      yielding nearly a racemic mixture of E and Z conformers. This finding helps to
      clear the paradoxical phenomenon between experimental results of mixed-valence
      complexes of E- and Z-1,2-bis(1'-ethyl-1-ferrocenyl)-1,2-dimethylethylene and
      theories. The stability of the mixed-valence species was discussed in terms of
      resonance delocalization, Coulomb repulsion energy, inductive effect, magnetic
      interaction, structural factors, and statistical factor. According to our
      analysis based on the Hush formalism, the contribution due to Coulomb repulsion
      energy dominates the overall stability of the mixed-valence state in 1+, 2+, and
      3+. Stabilization that arises from resonance delocalization is only minor and
      contributes less than 4% to the overall stability, even in 3+ where linked Cp
      rings and the ethylenic plane are coplanar. In calculating the resonance
      contribution, crystallographic Fe-Fe distances of 7.44 A (1) and 6.68 A (3) were
      used for 1+, and 3+, respectively.

PMID- 12526375
TI  - Xanthene-bridged cofacial bisporphyrins.
AB  - The synthesis and characterization of cofacial bisporphyrins juxtaposed by
      xanthene-bridged pillars are presented. The one-pot preparation of the xanthene
      dialdehyde avoids the lengthy bridge synthesis accompanying other cofacial
      porphyrin systems, thus allowing for the facile preparation of homobimetallic
      zinc (10), copper (11), and nickel (12) complexes. The cofacial orientation of
      the two porphyrin macrocycles was confirmed by X-ray crystallography. Structural
      data are provided for bisporphyrins 10-12: 10 (C79H82N8OZn2), triclinic, space
      group P1, a = 11.2671(2) A, b = 14.9809(2) A, c = 20.4852(2) A, alpha =
      101.6680(10) degrees, beta = 100.8890(10) degrees, gamma = 101.8060(10) degrees,
      Z = 2; 11 (C79H82N8OCu2), triclinic, space group P1, a = 11.21410(10) A, b =
      14.9539(5) A, c = 20.6915(7) A, alpha = 101.810(2) degrees, beta = 101.044(2)
      degrees, gamma = 101.722(2) degrees, Z = 2; 12 (C79H82N8ONi2), monoclinic, space
      group C2/c, a = 24.1671(4) A, b = 10.669 A, c = 50.5080(9) A, beta = 99.553(2)
      degrees, Z = 8. Exciton interactions between the porphyrin rings are apparent in
      electronic spectra, consistent with the cofacial superstructure. The combination
      of structural and spectroscopic data provides a basis for the design of
      additional metal derivatives for the activation of dioxygen and other small
      molecules.

PMID- 12526377
TI  - Dinuclear azolato-bridged complexes of the nickel group metals with haloaryl
      ligands: a reinvestigation of their behavior in solution.
AB  - A reinvestigation of the NMR spectra of the complexes (NBu4)2[M2(mu-LL)2R4] (M =
      Pd, Ni, Pt, LL = pyrazolate (pz), 3,5-dimethylpyrazolate (dmpz), 3
      methylpyrazolate (mpz), indazolate (indz), R = C6F5; M = Pd, LL = pz, dmpz, mpz,
      indz, R = 2,4,6-C6F3H2) shows that the boat-shaped dimeric structures of their
      anions are quite stable in solution, and the previously proposed fast equilibria
      or dissociations to give species such as [R2M(N-N)(acetone)]-, [R2M(acetone)2] +
      2dmpz-, or [R2M(N1-N2)(acetone)]- + [R2M(N2-N1)(acetone)]- in no case occur. A
      mixture of the two diastereoisomers (head-to-head, HH, and head-to-tail, HT) is
      present for the asymmetrically substituted azolates (mpz and indz), in a ratio
      ranging from 1:7 to 1:30 for the different complexes. Strong through-space
      coupling between the endo ortho fluorine nuclei of different MR2 fragments is
      observed in the 19F NMR spectra of these diastereoisomers whose boatlike
      structures place these atoms at short distances.

PMID- 12526376
TI  - Structural studies of the [tris(imidazolyl)phosphine]metal nitrate complexes
      [[PimPrl,But]M(NO3)]+ (M = Co, Cu, Zn, Cd, Hg): comparison of nitrate-binding
      modes in synthetic analogues of carbonic anhydrase.
AB  - X-ray diffraction studies on a series of cationic divalent metal nitrate
      complexes supported by the tris(1-isopropyl-4-tert-butylimidazolyl)phosphine
      ligand, [[PimPri,But]M(NO3)]+ (M = Co, Cu, Zn, Cd, Hg), demonstrate that the
      nitrate ligand coordination mode is strongly dependent upon the metal. With the
      exception of that for the HgII derivative, the nitrate ligand coordination modes
      correlate with the activities of metal-substituted carbonic anhydrases, such that
      the only MII-carbonic anhydrases which exhibit significant activity, i.e., the Zn
      and Co species, are those for which the [[PimPri,But]M(NO3)]+ complexes possess
      strongly asymmetric nitrate ligands. This trend supports the notion that access
      to a unidentate, rather than a bidentate, bicarbonate intermediate may be a
      critical requirement for significant carbonic anhydrase activity. Interestingly,
      the nitrate coordination modes in the series of group 12 complexes,
      [[PimPri,But]M(NO3)]+ (M = Zn, Cd, Hg), do not exhibit a monotonic periodic
      trend: the bidenticity is greater for the cadmium complex than for either the
      zinc or mercury complexes. Since HgII-carbonic anhydrase is inactive, the
      correlation between nitrate coordination mode and enzyme activity is anomalous
      for the mercury complex. Therefore, it is suggested that the inactivity of HgII
      carbonic anhydrase may be consequence of the reduced tendency of the mercury
      center in HgII-carbonic anhydrase to bind water.

PMID- 12526378
TI  - Reduced mono-, di-, and tetracubane-type clusters containing the [MoFe3S4]2+ core
      stabilized by tertiary phosphine ligation.
AB  - Treatment of oxidized clusters [(Cl4cat)(MeCN)MoFe3S4Cl3]2- (1) and
      [(Meida)MoFe3S4Cl3]2- (2) with tertiary phosphines in the presence of NaBPh4 in
      acetonitrile results in chloride substitution at the iron sites and the formation
      of clusters with the reduced [MoFe3S4]2+ core. Thus, 1 is a precursor to
      [(Cl4cat)(MeCN)MoFe3S4(PR3)3] (R = But (3), Pri (4)) and
      [(Cl4cat)2(Et3P)2Mo2Fe6S8(PEt3)4] (5). Cluster 2 affords
      [[(Meida)MoFe3S4(PCy3)3]4Fe2(mu-Cl)L2]3+ (L = THF (6), MeCN (7)). The structures
      of 3-7 were established by X-ray analysis. Clusters 3 and 4 are single cubanes,
      centrosymmetric 5 (previously reported in a different space group: Demadis, K.
      D.; Campana, C. F.; Coucouvanis, D. J. Am. Chem. Soc. 1995, 117, 7832) is a
      double cubane with a rhomboidal Fe2S2 bridge, and 6 and 7 are tetracubanes. In
      the latter, four Meida oxygen atoms from different cubanes bind each of two
      central high-spin Fe(II) atoms in trans-Fe(mu-Cl)LO4 coordination. The topology
      of these clusters is not precedented. Zero-field Mossbauer parameters for all
      clusters are reported. Isomer shift considerations suggest the formulation
      [Mo3+Fe2+2Fe3+S4] for reduced clusters. Voltammetry of 3 and 4 reveals four
      member electron transfer series encompassing the oxidation levels
      [MoFe3S4]4+,3+,2+,+ in the potential interval + 1.0 to -1.3 V vs SCE in
      dichloromethane. Compared to the clusters with monoanionic ligands at the iron
      sites, phosphine ligation shifts redox potentials to more positive values. This
      effect arises from reduction of cluster negative charge and the tendency of
      phosphines to stabilize lower oxidation states. The synthesis of reduced clusters
      4 from 1 and of [Fe4S4(PPri3)4]+ from [Fe4S4Cl4]2- is accompanied by the
      formation of Pri3PS, detected by 31P NMR, indicating that the phosphine is the
      reductant. This result implies a similar function of tertiary phosphines in the
      synthesis of 3 and 5-7. (Cl4cat = tetrachlorocatecholate(2-); Meida = N
      methyliminodiacetate(2-).)

PMID- 12526379
TI  - Characterization and X-ray absorption spectroscopic studies of bis[quinato(2
      )]oxochromate(V).
AB  - A new Cr(V) complex, K[CrVO(qaH3)2].H2O (Ia; qaH3 = quinato = (1R,3R,4R,5R)
      1,3,4,5-tetrahydroxycyclohexanecarboxylato(2-)), synthesized by the reaction of
      K2Cr2O7 with excess qaH5 in MeOH (Codd, R.; Lay, P. A. J. Am. Chem. Soc. 1999,
      121, 7864-7876), has been characterized by microanalyses, electrospray mass
      spectra, and UV-visible, CD, IR, EPR, and X-ray absorption spectroscopies. This
      complex is of interest because of its ability to act as both a structural and a
      biomimetic model for a range of Cr(V) species believed to be generated in vivo
      during the intracellular reduction of carcinogenic Cr(VI). The Na+ analogue of Ia
      (Ib) has also been isolated and characterized by microanalyses and IR and X-ray
      absorption spectroscopies. The reaction of Cr(VI) with MeOH in the presence of
      qaH5 that leads to I proceeds via a Cr(IV) intermediate (observed by UV-visible
      spectroscopy), and a mechanism for the formation of I has been proposed. DMF or
      DMSO solutions of I are stable for several days at 25 degrees C, while I in
      aqueous solution (pH = 4) disproportionates to Cr(VI) and Cr(III) in minutes. The
      likely structures in the solid state for Ia (14 K) and Ib (approximately 293 K)
      have been determined using both single-scattering (Ia,b) and multiple-scattering
      (Ia) analyses of XAFS data. These analyses have shown the following: (i) In
      agreement with the results from the other spectroscopic techniques, the quinato
      ligands are bound to Cr(V) by 2-hydroxycarboxylato moieties, with Cr-O bond
      lengths of 1.55, 1.82, and 1.94 A for the oxo, alcoholato, and carboxylato O
      atoms, respectively. (ii) The position of an oxo O atom is somewhat disordered.
      This is consistent with molecular mechanics modeling of the likely structures.
      The XAFS, EPR, and IR spectroscopic evidence points to the existence of hydrogen
      bonds between the oxo ligand and the 3,4,5-OH groups of the quinato ligands in
      the solid state of I.

PMID- 12526380
TI  - Synthesis and structure of the cluster ion pair [Ru3(CO)9[mu
      P(NPri2)2]3][Ru6(CO)15(mu 6-C)[mu-P(NPri2)2]]. A theoretical overview of M3(mu
      PR2)3 frameworks.
AB  - The compound [Ru3(CO)9[mu-P(NPri2)2]3][Ru6(CO)15(mu 6-C)[mu-P(NPri2)2]] (1),
      obtained via the addition of PCl(NPri2)2 to K2[Ru4(CO)13], crystallizes in the
      monoclinic space group P2l/c with a = 15.537(8) A, b = 36.151(16) A, c =
      19.407(5) A, beta = 91.14(2) degrees, Z = 4, and R = 0.069 for 8006 observed
      reflections. The unit cell is unusual in that it contains both a typical
      octahedral Ru6 cluster anion (1a), featuring an encapsulated carbide, and a
      symmetrical phosphido bridge, in addition to a 50-electron trinuclear cluster
      cation [Ru3(CO)9[mu-P(NPri2)2]3]+ (1c). The latter, with approximate D3h
      symmetry, exhibits long Ru-Ru distances (> or = 3.15 A). Among the family of
      clusters with M3(mu-PR2)3 cores and different numbers of both electrons (TEC) and
      terminal ligands (LxLyLz), 1c is unique in that it is a 333 stereotype with 50
      valence electrons. MO calculations permit us to predict the existence of redox
      congeners of 1c clusters and related 48e Re3 clusters. This work also presents a
      summary of the relationships between the electronic and the geometric structures
      for all known M3LxLyLz(mu-PR2)3 species. The basic stereochemical features are
      influenced by the total-electron count and, hence, by the degree of M-M bonding,
      as well as the remarkable flexibility of the phosphido bridging ligands. The mu
      PR2 ligands need not necessarily lie in the M3 plane, and a wide range of M-P-M
      angles (as small as 72 degrees or as large as 133 degrees) have been observed.

PMID- 12526381
TI  - The solid-state electrochemistry of metal octacyanomolybdates,
      octacyanotungstates, and hexacyanoferrates explained on the basis of dissolution
      and reprecipitation reactions, lattice structures, and crystallinities.
AB  - The electrochemical behavior of solid microparticles of metal (Ag+, Cd2+, Co2+,
      Cr2+, Cu2+, Fe2+, Mn2+, Ni2+, Pb2+, and Zn2+) octacyanomolybdates,
      octacyanotungstates, and hexacyanoferrates has been studied by voltammetry,
      electrochemical quartz crystal microbalance, and microscopic diffuse reflectance
      spectroelectrochemical measurements. The solid microparticles have been
      immobilized on the surface of graphite electrodes prior to the electrochemical
      measurements. A comparative study of the cyclic oxidation and reduction of these
      compounds in the presence of potassium ions revealed that any interpretation of
      the electrochemistry requires the solubility equilibria of the reduced compounds
      to be taken into account, such as in the case of the silver salts [Ag3K[X]] and
      [Ag4[X]] (with X = FeII(CN)6(4-), MIV(CN)8(4-) (M = Mo, W)). Because [Ag4[X]] has
      a lower solubility than [Ag3K[X]], the electrochemistry is accompanied by a
      conversion of solid [Ag3K[X]] into solid [Ag4[X]]. Two distinct voltammetric
      signal systems are generated by these two compounds according to [Ag3K[X]]
      reversible [Ag3[X]] + K(+) + e- and [Ag4[X]] reversible [Ag3[X]] + Ag(+) + e-.
      When silver ions are present in the solution adjacent to the microparticles, the
      silver octacyanometalates and silver hexacyanoferrate show a chemically
      reversible and very stable voltammetric behavior. Despite the fact that the
      electrochemistry is based upon a single-electron/single-ion transfer reaction
      ([Ag4[X]] reversible [Ag3[X]] + Ag(+) + e-), more than one electrochemical signal
      is observed because of the simultaneous presence of amorphous and crystalline
      particles. This study shows that the interplay of solubility equilibria and
      electrochemical equilibria is generally observed for the other metal
      octacyanomolybdates, octacyanotungstates, and hexacyanoferrates as well.

PMID- 12526382
TI  - Phosphate diester hydrolysis by mono- and dinuclear lanthanum complexes with an
      unusual third-order dependence.
AB  - A series of mono- and dinuclear lanthanum complexes of 15,31-dimethyl
      3,11,19,27,33,35-hexaazapentacyclo[27.3.1.1.(5,9)1,(13,17).
      1(21,25)]hexatriaconta-5,7,9(33),13,15,17(34),21,23,25(35),29,31, 1(36)-dodecaene
      34,36-diol (24RBPyBC, L) have been defined in solution. Their ability to
      hydrolyze bis(4-nitrophenyl) phosphate, a phosphate diester, was studied. The
      various metal-coordinated hydroxide nucleophiles that form in solution attack the
      substrate in the hydrolysis reaction. The dihydroxo dilanthanum complex, L-2La
      2(OH), is the most effective catalyst. Its rate constant is 75 times larger than
      the rate constant for the monohydroxo dilanthanum complex, L-2La-OH. The
      mononuclear complexes are not as successful as the dinuclear complexes because
      they have fewer metal ions per complex to act as Lewis acids. They also cannot
      generate hydroxide nucleophiles at low pH values like the dinuclear complexes
      can. The reaction has an unusual third-order dependence on the catalyst
      concentration which is valid for the dinuclear complexes as well as the
      mononuclear complexes. This implies a mechanism where a metal-coordinated
      hydroxide nucleophile attacks the phosphorus of the substrate on the side
      opposite the negatively charged oxygens.

PMID- 12526383
TI  - Conversion of core oxos to water molecules by 4e-/4H+ reductive dehydration of
      the Mn4O2(6+) core in the manganese-oxo cubane complex Mn4O4(Ph2PO2)6: a partial
      model for photosynthetic water binding and activation.
AB  - Reaction of the Mn4O4(6+) "cubane" core complex, Mn4O4L6 (1) (L =
      diphenylphosphinate, Ph2PO2-), with a hydrogen atom donor, phenothiazine (pzH),
      forms the dehydrated cluster Mn4O2L6 (2), which has lost two mu-oxo bridges by
      reduction to water (H2O). The formation of 2 was established by electrospray mass
      spectrometry, whereas FTIR spectroscopy confirmed the release of water molecules
      into solution during the reduction of 1. UV-vis and EPR spectroscopies
      established the stoichiometry and chemical form of the pzH product by showing the
      production of 4 equiv of the neutral pz radical. By contrast, the irreversible
      decomposition of 1 to individual Mn(II) ions occurs if the reduction is performed
      using electrons provided by various proton-lacking reductants, such as
      cobaltocene or electrochemical reduction. Thus, cubane 1 undergoes coupled four
      electron/four-proton reduction with the release of two water molecules, a
      reaction formally analogous to the reverse sequence of the steps that occur
      during photosynthetic water oxidation leading to O2 evolution. 1H NMR of
      solutions of 2 reveal that all six of the phosphinate ligands exhibit
      paramagnetic broadening, due to coordination to Mn ions, and are magnetically
      equivalent. A symmetrical core structure is thus indicated. We hypothesize that
      this structure is produced by the dynamic averaging of phosphinato ligand
      coordination or exchange of mu-oxos between vacant mu-oxo sites. The paramagnetic
      1H NMR of water molecules in solution shows that they are able to freely exchange
      with water molecules that are bound to the Mn ion(s) in 2, and this exchange can
      be inhibited by the addition of coordinating anions, such as chloride. Thus, 2
      possesses open or labile coordination sites for water and anions, in contrast to
      solutions of 1, which reveal no evidence for water coordination. Complex 2
      exhibits greater paramagnetism than that of 1, as seen by 1H NMR, and it
      possesses a broad (440 G wide) EPR absorption, centered at g = 2, that follows a
      Curie-Weiss temperature dependence (10-40 K) and is visible only at low
      temperatures, compared to EPR-silent 1. Its comparison to a spin-integration
      standard reveals that 2 contains 2 equiv of Mn(II), which is in agreement with
      the formal oxidation state of 2Mn(II)2Mn(III) that was derived from the
      titration. The EPR and NMR data for 2 are consistent with a loss of two of the
      intermanganese spin-exchange coupling pathways, versus 1, which results in two
      "wingtip" Mn(II) S = 5/2 spins that are essentially magnetically uncoupled from
      the diamagnetic Mn2O2 base. Bond-enthalpy data, which show that O2 evolution via
      the reaction 1-->2 + O2, is strongly favored thermodynamically but is not
      observed in the ground state due to an activation barrier, are included. This
      activation barrier is hypothesized to arise, in part, from the constraining
      effect of the facially bridging phosphinate ligands.

PMID- 12526384
TI  - Chemistry of thiocarboxylates: synthesis and structures of neutral copper(I)
      thiocarboxylates with triphenylphosphine.
AB  - The reactions of Na+ R[O]CS- (R = Me, Ph) with mixtures of CuCl and PPh3 in
      stoichiometric ratios yielded the compounds [Cu4(SC[O]Me)4(PPh3)4] (1),
      [Cu4(SC[O]Ph)4(PPh3)3] (2), [Cu2(SC[O]Me)2(PPh3)4] (3), [Cu(SC[O]Ph)(PPh3)2] (4),
      and [Cu2(SC[O]Ph)2(PPh3)3] (5) quantitatively. Compound 2 was also obtained from
      mixtures of CuCl, PPh3, and NaSC[O]Ph in the ratio 1:1:1. The analogous
      thioacetate compound similar to 2 and the thiobenzoate analogue of 1 could not be
      obtained. Attempts to prepare the unsymmetrical dimer of a thioacetate compound
      similar to 5 gave a mixture of 1 and 3. The structures of 1-4 have been
      determined by single-crystal X-ray diffraction methods. Crystal data for 1:
      triclinic space group Pl, a = 11.5844(3) A, b = 13.2459(3) A, c = 14.3433(3) A,
      alpha = 64.019(1) degrees, beta = 79.297(1) degrees, gamma = 69.426(1) degrees, V
      = 1850.98(7) A3, Z = 1, Dcalcd = 1.439 g.cm-3. Crystal data for 2.0.5CH2Cl2.H2O:
      triclinic space group P1, a = 12.4413(1) A, b = 15.5443(1) A, c = 20.4637(3) A,
      alpha = 94.974(1) degrees, beta = 95.976(1) degrees, gamma = 100.450(1) degrees,
      V = 3848.09(7) A3, Z = 2, Dcalcd = 1.416 g.cm-3. Single-crystal data for 3:
      monoclinic space group P2(1)/n, a = 15.2746(2) A, b = 23.2947(2) A, c =
      19.0518(3) A, beta = 96.713(1) degrees, V = 6732.5(2) A3, Z = 4, Dcalcd = 1.309
      g.cm-3. Crystal data for 4: triclinic space group P1, a = 10.2524(3) A, b =
      12.9826(4) A, c = 14.5340(4) A, alpha = 87.723(1) degrees, beta = 75.322(1)
      degrees, gamma = 75.978(1) degrees, V = 1815.14(9) A3, Z = 2, Dcalcd = 1.327 g.cm
      3. Compound 1, [mu 3-SC[O]Me-S)2(mu-SC[O]Me-S)2(CuPPh3)4], is a tetramer with a
      distorted stepladder structure in which two copper atoms are trigonally
      coordinated and the other two are tetrahedrally coordinated. Two bonding modes,
      namely, mu 3-S and mu 2-S, were observed for the Me[O]CS- anion. The structure of
      2 may be described as a highly distorted cubanoid structure and formulated as
      [(mu 3-SC[O]Ph-S3)(mu 3-SC[O]Ph-S2,O)3(Cu)(CuPPh3)3]. In 2, three copper atoms
      have tetrahedral coordination geometry and one copper atom is trigonally
      coordinated. Unprecedented bonding modes, namely, mu 3-S, have been observed for
      the R[O]CS- anions, in 1 and 2 and mu 3-S2,O in 2. Compound 3, [(mu-SC[O]MeS)(mu
      SC[O]Me-S,O)[Cu(PPh3)2]2] is a dimer with mu 2-S and mu 2-S,O bonding modes of
      Me[O]CS- ligands. Monomeric structure was found in 4 in which the copper atom has
      trigonal planar geometry with a very weak intramolecular interaction with O.
      Variable temperature 31P NMR studies in solution show the presence of various
      species in equilibria.

PMID- 12526385
TI  - Silver(I) coordination polymers using thioether macrocycle building blocks.

PMID- 12526386
TI  - A dinuclear cation with both four- and five-coordinate cobalt(II).

PMID- 12526387
TI  - Structural and solution calorimetric studies of sulfur binding to nucleophilic
      carbenes.

PMID- 12526388
TI  - Facile syntheses and structures of new metal-maleonitrilediselenolates [K([2.2.2]
      cryptand)]3[Ag(Se2C2(CN)2)(Se6)], [K([2.2.2]-cryptand)]2[Ni(Se2C2(CN)2)2], and
      Ni(dppp)(Se2C2(CN)2).

PMID- 12526389
TI  - Single crystal and solution complex structure of Nd(CO3)(4)5-. The first
      characterization of a mononuclear lanthanide(III) carbonato complex.

PMID- 12526390
TI  - Electrocatalysis in photochemically activated electropolymerized thin films.
AB  - In reductively electropolymerized thin films of poly-cis-[Ru(vbpy)2(py)2](PF6)2
      ("vbpy" is 4-methyl-4'-vinyl-2,2'-bipyridine and "py" is pyridine), on glassy
      carbon electrodes, photochemical ligand loss with aqueous HClO4 in the external
      solution occurs to give poly-cis-[Ru(vbpy)2(OH2)2](ClO4)2, but the efficiency of
      ligand loss is greatly decreased compared to the efficiency in solution. In
      cyclic voltammograms of films containing the aqua complex, there is evidence for
      both RuIII/II and higher oxidation state RuIV/III, RuV/IV, and RuVI/V couples.
      The redox chemistry of the resulting films is dictated by the film structure and
      can be controlled by varying the electropolymerization conditions and external
      solution composition. The oxidation of alcohols by these higher oxidation state
      couples has been investigated electrochemically.

PMID- 12526391
TI  - From simple trans-[a2Pt(2-hydroxypyrimidine)2]2+ (a = NH3, CH3NH2) complexes to
      structures of higher complexity. Molecular recognition of 2-aminopyrimidine by
      hydrogen bond formation and reactivity toward additional metal ions.
AB  - The new complexes trans-[a2Pt(Hpymo-N1)2]X2 (a = NH3, X = NO3 (1a); a = CH3NH2, X
      = NO3 (1b); a = CH3NH2, X = ClO4 (1c); Hpymo = 2-hydroxypyrimidine) have been
      prepared by reaction of trans-[a2Pt(H2O)2]-X2 with 2-hydroxypyrimidine at 80
      degrees C in water. Complex 1c cocrystallizes in water with 2-aminopyrimidine
      (ampym) through formation of complementary pairs of hydrogen bonds to give the
      supramolecular hexagon [trans-[(CH3NH2)2Pt(pymo-N1)(Hpymo-N1)].Hampym[2(ClO4)4
      (2). Molecular recognition of ampym by 1c is responsible for a conformational
      change of the two hydroxypyrimidine ligands in 1c from anti (1c) to syn and in
      addition for a proton transfer from a Hpymo residue to ampym against 1.5 units of
      pKa gradient. 1H NMR concentration-dependent studies as well as NOE experiments
      in dmso-d6 and dmf-d7 show that 2 dissociates in solution. Compound 1a reacts in
      NH3:H2O (1:3) with AgI to give the polymeric species [trans-[(NH3)2Pt(mu-pymo
      N1,N3)2Ag(H2O)]-NO3]n (3). In contrast to 2, in the polymeric structure the trans
      [NH3)2Pt(pymo)2] entities adopt an anti conformation. Nevertheless, the
      [(H2O)Ag(pymo)2] residues present a syn conformation that leads to a meander-like
      global structure. Compounds 1b, 1c, 2, and 3 have been studied by X-ray
      crystallography: (1b) triclinic space group, P1, a = 9.300(2) A, b = 10.483(2) A,
      c = 11.050(2) A, alpha = 68.21(3) degrees, beta = 75.47(3) degrees, gamma =
      73.83(3) degrees, Z = 2, R1 = 0.025, and wR2 = 0.062; (1c) triclinic space group,
      P1, a = 5.692(1) A, b = 7.758(2) A, c = 11.236(2) A, alpha = 93.12(3) degrees,
      beta = 92.86(3) degrees, gamma = 102.58(3) degrees, Z = 2, R1 = 0.048, and wR2 =
      0.119; (2) triclinic space group, P1, a = 8.355(2) A, b = 11.221(2) A, c =
      13.004(3) A, alpha = 86.76(3) degrees, beta = 78.62(3) degrees, gamma = 77.96(3)
      degrees, Z = 2, R1 = 0.033, and wR2 = 0.080; (3) monoclinic space group, C2/c, a
      = 5.345(1) A, b = 23.998(5) A, c = 12.474(2) A, beta = 102.27(3) degrees, Z = 8,
      R1 = 0.041, and wR2 = 0.093.

PMID- 12526392
TI  - The structure of arachno-[B6H11]-, at -25 degrees C in (CD3)2O, is resolved via
      the ab initio/IGLO-GIAO/NMR procedure.
AB  - The arachno-[B6H11]- solution structure at -25 degrees C was clarified as
      fluxional compound 2 by applying the ab initio/IGLO/NMR method. The anion 2 can
      be derived from arachno-B6H12, 1, by the removal of the B2/B3 bridging hydrogen
      (2). No minimum on the potential energy surface could be found for an asymmetric
      complex, a, between [B5H8]- and BH3, which had been proposed originally. A Cs
      symmetric [mu-(BH3)B5H8]- complex, A, only 3.2 kcal mol-1 higher in energy than
      2, is the intermediate in the fluxional rearrangement observed on the NMR time
      scale. The transition structure [D] connecting 2 (Erel = 0.0) and A (Erel = 3.2)
      has a relative energy of 9.7 kcal mol-1. The elimination of both a and A as "most
      stable structure" candidates of arachno-[B6H11]- reinforces the early geometrical
      bonding systematics for boranes and carboranes.

PMID- 12526393
TI  - Microcalorimetric determination of thermodynamic parameters for ionophore
      siderophore host-guest complex formation.
AB  - Thermodynamic parameters (delta H, delta S, and delta G) were determined by
      microcalorimetry in wet chloroform for host-guest assembly formation involving
      second-sphere complexation of the siderophore ferrioxamine B by crown ether (18
      crown-6, cis-dicyclohexano-18-crown-6, benzo-18-crown-6) and cryptand (2.2.2
      cryptand) hosts. Similar data were also collected for the same hosts with the
      pentylammonium ion guest, which corresponds to the pendant pentylamine side chain
      of ferroxamine B. Host-guest assembly formation constants (Ka) obtained from
      microcalorimetry agree with values obtained indirectly from chloroform/water
      extraction studies in those cases where comparable data are available. On the
      basis of a trend established by the pentylammonium guest, an enhanced stability
      relative to the crown ethers is observed for the assembly composed of
      ferrioxamine B and 2.2.2 cryptand that is due to entropic effects. Trends in
      delta H and delta S with changes in host and guest structure are discussed and
      attributed directly to host-guest complex formation, as solvation effects were
      determined to be insignificant (delta Cp = 0).

PMID- 12526394
TI  - Structural trends in first-row transition-metal bis(benzimidazole) complexes.
AB  - Dimethyl-substituted bis(benzimidazole) (Me2BBZ) is a novel macrocyclic ligand
      that possesses an intrinsic nonplanarity. To examine how metal-ion binding
      affects the magnitude of this nonplanarity, we have determined the structures of
      a periodic series of Me2BBZ complexes bound to Mn(II), Fe(II), Co(II), Ni(II),
      and Cu(II). These studies demonstrate that the extent of ligand ruffling and
      metal doming is indeed influenced by the nature of the metal. Concomitant with
      the periodic decrease of the ionic radii of the encapsulated divalent metal ion,
      a decrease in the magnitude of both the ligand nonplanarity and the metal out-of
      the-plane distance is observed. For the metal out-of-the-plane distance, this
      correlation persists until the metal finally moves into the mean ligand plane.
      For the nonplanar distortion, the extent of the nonplanarity decreases to a
      limiting value that is intrinsic to the Me2BBZ ligand due to steric factors.
      These observations indicate that the relative sizes of the metal ion and the
      Me2BBZ ligand cavity have profound effects on the structural features of the
      metal-ligand complex.

PMID- 12526395
TI  - Deprotonation of cationic tungsten(IV) aqua-oxo-alkyne complexes to form dioxo
      vinyl tungsten(VI) complexes.
AB  - Chiral tungsten(IV) aqua-oxo-alkyne complexes, [Tp'W(O)(H2O)(RC identical to
      CR)][OTf] (R = H (1); R = Me (2)); (Tp' = hydridotris(3,5
      dimethylpyrazolyl)borate; OTf = trifluoromethanesulfonate), have been prepared by
      halide abstraction from iodide precursors. These cationic complexes have been
      characterized with triflate as the counteranion. The tautomeric dihydroxo isomer
      has not been observed. The neutral triflate adduct Tp'W(O)(OTf)(HC identical to
      CH) (3) has also been isolated. Cationic complexes 1 and 2 undergo deprotonation
      and isomerization when exposed to Al2O3 to give the dioxo-vinyl compounds
      Tp'W(O)2(CH=CH2) (6) and Tp'W(O)2[C(Me)=C(H)(Me)] (7), reflecting the conversion
      of the WIV(OH)(RC identical to CR) fragment to WVI(=O)(RC=CHR). The presumed
      intermediates, neutral oxo-hydroxo compounds Tp'W(O)(OH)(RC identical to CR) (R =
      H (9); R = Me (10)), can be accessed by deprotonation of 1 or 2 with NaOH.
      Conversion of 9 to 6 was achieved thermally upon heating at 100 degrees C for 2
      days. X-ray structural data have provided solid-state structures of both the
      cationic aqua complex 2 and the dioxo-vinyl complex 6.

PMID- 12526396
TI  - Coordination chemistry of a novel tetramacrocyclic ligand derived from 1,4,7
      triazacyclononane: synthesis, structure, and properties of nickel(II) and
      copper(II) complexes.
AB  - A new polynucleating ligand, 1,2,4,5-tetrakis(1,4,7-triazacyclonon-1
      ylmethyl)benzene (Ldur), has been prepared and characterized as its
      dodecahydrobromide salt. Addition of base to an aqueous solution of this salt and
      4 molar equivalents (m.e.) of a Ni(II) salt produces a mixture of bi- and
      trinuclear complexes, which can be separated by cation-exchange chromatography
      (CEC) and crystallized as [Ni2Ldur](ClO4)(4).2H2O (1) and
      [Ni3Ldur(H2O)6](ClO4)(6).9H2O (2). The "full capacity" tetranuclear complex,
      [Ni4Ldur(H2O)12](ClO4)(8).8H2O (3), is obtained by slow addition of Ldur to a
      refluxing aqueous solution of excess Ni2+ ions, followed by CEC purification.
      Treatment of Ldur with 4 m.e. of a copper(II) salt produces exclusively the
      tetranuclear complex, [Cu4Ldur(H2O)8](ClO4)(8).9H2O (4), while reaction with only
      2 m.e. of Cu2+ ions yields the binuclear complex, [Cu2Ldur](ClO4)(4).4H2O (5).
      The X-ray structures of complexes 1,2,4, and [Cu2Ldur](ClO4)(4).3H2O (5') have
      been determined; all are monoclinic, P2(1)/c: for 1, a = 9.497(3) A, b =
      13.665(5) A, c = 19.355(6) A, beta = 100.57(2) degrees, V = 2469(1) A3, and Z =
      2; for 2, a = 22.883(7) A, b = 15.131(6) A, c = 20.298(8) A, beta = 97.20(3)
      degrees, V = 6973(4) A3, and Z = 4; for 4, a = 16.713(7) A, b = 16.714(6) A, c =
      14.775(11) A, beta = 108.24(5) degrees, V = 3920(4) A3, and Z = 2; and for 5', a
      = 9.5705(1) A, b = 13.0646(1) A, c = 20.1298(2) A, beta = 103.1618(8) degrees, V
      = 2450.81(4) A3, and Z = 2. The metal centers in 1 and 5' lie in distorted
      octahedral environments, each facially coordinated by two of the triamine rings
      of Ldur, the cation in each case being centrosymmetric. In 2, one of the
      nickel(II) centers is similarly sandwiched by two triamine rings, while the other
      two nickel(II) centers are each coordinated by a single triamine ring from the
      ligand, with their distorted octahedral coordination spheres each being completed
      by three water molecules. In 4, the four triamine rings of Ldur bind to separate
      copper(II) centers, with two water molecules occupying the remaining two sites of
      the distorted square pyramidal (SP) coordination spheres, the cation again being
      centrosymmetric.

PMID- 12526397
TI  - Structural studies on single crystals of Chevrel phase selenides REMo6Se8 (RE =
      La, Ce, Pr, Nd, or Sm) at 298 K.
AB  - We report on structural studies at room temperature of rare-earth based Chevrel
      phase selenides of the formula RExMo6Se8, where RE stands for a light rare-earth
      La (1), Ce (2), Pr (3), Nd (4), or Sm (5). The single crystals were grown at 1650
      degrees C < T < 1690 degrees C from off-stoichiometric starting compositions,
      with the exception of 3, which was grown at 1710 degrees C from a stoichiometric
      charge (congruently melting material). The crystal structures were solved in
      space group R3 (No. 148; Z = 1) and found to be isostructural with the well-known
      Chevrel phases having large cations (e.g., PbMo6S8, REMo6S8). The structures are
      based on Mo6Se8 metallic clusters that are slightly rotated inside a pseudocubic
      rare-earth sublattice. Structural refinements revealed that the origin site,
      occupied by the RE atoms, exhibits slight deficiencies, leading to a RExMo6Se8
      composition, with x ranging between approximately 0.82 and approximately 0.92: 1
      La0.88Mo6Se8, arh = 6.7577(9) A, alpha rh = 88.62(2) degrees; 2a Ce0.82Mo6Se8,
      arh = 6.7407(6) A, alpha rh = 88.83(2) degrees; 2b Ce0.92Mo6Se8, arh = 6.7473(9)
      A, alpha rh = 88.69(2) degrees; 3 Pr0.86Mo6Se8, arh = 6.7385(6) A, alpha rh =
      88.81(2) degrees; 4 Nd0.85Mo6Se8, arh = 6.7286(5) A, alpha rh = 88.85(1) degrees;
      and 5 Sm0.87Mo6Se8, arh = 6.7182(2) A, alpha rh = 88.956(3) degrees. All of the
      structural data presented in this work (lattice constants, positional parameters
      and interatomic distances) concern an average RE content of x approximately 0.87.
      In this way, any influence due to electronic effects (VEC number) can be
      discarded, and exact correlations between these parameters and the ionic radius
      of the rare-earth atoms can then be established.

PMID- 12526398
TI  - Metal complexes of N-tosylamidoporphyrin: cis-acetato-N-tosylimido-meso
      tetraphenylporphyrinatothallium(III) and trans-acetato-N-tosylimido-meso
      tetraphenylporphyrinatogallium(III).
AB  - The crystal structures of acetato-N-tosylimido-meso
      tetraphenylporphyrinatothallium(III), Tl(N-NTs-tpp)(OAc) (1), and acetato-N
      tosylimido-meso-tetraphenylporphyrinatogallium(III), Ga(N-NTs-tpp)(OAc) (2), were
      determined. The coordination sphere around the Tl3+ ion is a distorted square
      based pyramid in which the apical site is occupied by a chelating bidentate OAc-
      group, whereas for the Ga3+ ion, it is a distorted trigonal bipyramid with O(3),
      N(3), and N(5) lying in the equatorial plane. The porphyrin ring in the two
      complexes is distorted to a large extent. For the Tl3+ complex, the pyrrole ring
      bonded to the NTs ligand lies in a plane with a dihedral angle of 50.8 degrees
      with respect to the 3N plane, which contains the three pyrrole nitrogens bonded
      to Tl3+, but for the Ga3+ complex, this angle is found to be only 24.5 degrees.
      In the former complex, Tl3+ and N(5) are located on the same side at 1.18 and
      1.29 A from its 3N plane, but in the latter one, Ga3+ and N(5) are located on
      different sides at -0.15 and 1.31 A from its 3N plane. The free energy of
      activation at the coalescence temperature Tc for the intermolecular acetate
      exchange process in 1 in CD2Cl2 solvent is found to be delta G++171 = 36.0 kJ/mol
      through 1H NMR temperature-dependent measurements. In the slow-exchange region,
      the methyl and carbonyl (CO) carbons of the OAc- group in 1 are separately
      located at delta 18.5 [3J(Tl-13C) = 220 Hz] and 176.3 [2J(Tl-13C) = 205 Hz] at 
      110 degrees C.

PMID- 12526399
TI  - Theoretical study of the mechanisms of palladation of methylenecyclopropane and
      [3 + 2] cycloadditions.
AB  - Palladation of methylenecyclopropane and [3 + 2] cycloaddition with alkenes have
      been studied theoretically. In palladium complexes of methylenecyclopropane or
      trimethylenemethane, the eta 2 forms have been shown to be more stable than the
      palladacyclobutane forms. However, the barrier heights to yield
      palladacyclobutanes are not very high and the methylene-bridged carbon can be
      converted to the metal-attached carbon on palladium via a ring-opened transition
      state, allowing the scrambling of hydrogens in methylenecyclopropane. With
      respect to the palladium-catalyzed [3 + 2] cycloaddition reaction of
      methylenecyclopropane with alkenes, the path via palladacyclobutanes has been
      demonstrated to be more favorable than the path via an eta 2 complex. These
      results are discussed by using the paired interaction orbital scheme.

PMID- 12526400
TI  - Unusual coordination mode of thiosemicarbazone ligands. A search for the origin.
AB  - Twelve mixed-ligand thiosemicarbazone complexes of ruthenium and osmium, ten of
      general formula [M(bpy)2(bztsc-R)]ClO4, (M = Ru, Os; bpy = 2,2'-bipyridine,
      Hbztsc-R = benzaldehyde thiosemicacbazone) and two of type [M(bpy)2(actsc)]ClO4
      (Hactsc = acetonethiosemicarbazone), have been synthesized and characterized. All
      the complexes are diamagnetic (low-spin d6, S = 0) and in acetonitrile solution
      show several intense metal-to-ligand charge-transfer (MLCT) transitions in the
      visible region. Structures of Hbztsc-OMe, [Ru(bpy)2(bztsc-NO2)]ClO4 and
      [Ru(bpy)2(actsc)]ClO4 have been determined by X-ray crystallography. Benzaldehyde
      thiosemicarbazone exists in the thione form with the phenyl group trans to the
      hydrazinic nitrogen. The benzaldehyde thiosemicarbazone ligand coordinates to the
      metals through the hydrazinic nitrogen and sulfur with a bite angle of
      approximately 67 degrees, forming a four-membered chelate ring. However, the
      actsc ligand coordinates through the imine nitrogen and sulfur, forming a five
      membered chelate ring with a bite angle of approximately 81 degrees. The
      difference in coordination modes of two types of thiosemicarbazone ligands, viz.,
      bztsc-R and actsc, appears to result from the difference in steric bulk of the
      aryl and methyl group trans to the hydrazinic nitrogen. In acetronitrile solution
      they all show a reversible metal(II)-metal(III) oxidation in the range 0.18-0.58
      V vs SCE followed by an irreversible oxidation in the range 1.11-1.60 V vs SCE.
      Two successive one-electron reductions of the coordinated bipyridine are also
      observed in the range -1.53 to -1.96 V vs SCE.

PMID- 12526401
TI  - Redox characteristics of nickel and palladium complexes of the open-chain
      tetrapyrrole octaethylbilindione: a biliverdin model.
AB  - Octaethylbiliverdin, C35H46N4O2, is a linear tetrapyrrole that can exist in
      coordinated form as the fully reduced trianion (OEB)3-, as the two electron
      oxidized monoanion, (OEBOx)-, or as the one electron oxidized radical, (OEB.)2-.
      The three-membered electron-transfer series involving [M(OEB)]n with n = +1, 0,
      and -1, and M = Ni or Pd has been characterized electrochemically. The most
      highly oxidized members of these series have been isolated in the form of their
      diamagnetic triiodide salts, [NiII(OEBOx)]I3 and [PdII(OEBOx)]I3, and
      characterized spectroscopically and by X-ray diffraction. [NiII(OEBOx)]I3
      crystallizes in the orthorhombic space group Pbcn with a = 15.121(3) A, b =
      16.777(3) A, and c = 14.628(3) A at 130(2) K with Z = 4. Refinement of 3311
      reflections with 209 parameters and no restraints yielded wR2 = 0.136 and R =
      0.054 for 2643 reflections with I > 2 sigma(I). The structure involves helical
      coordination of the linear tetrapyrrole ligand about the nickel with all four
      nitrogen atoms coordinated to the metal and Ni-N distances of 1.867(5) and
      1.879(5) A. The triiodide ion is not coordinated to the nickel but sits over one
      of the meso carbon atoms of the tetrapyrrole. In the solid state, pairs of
      [NiII(OEBOx)]+ crystallize about a center of symmetry so that two identical
      tab/slot hydrogen-bonded arrangements involving the lactam oxygen of one complex
      and methine and two methylene protons of the adjacent cation. Similar hydrogen
      bonded motifs are found in other complexes derived from octaethylbilindione.
      [PdII(OEBOx)]I3 is isomorphic with the nickel analogue and crystallizes in the
      orthorhombic space group Pbcn with a = 15.2236(6) A, b = 16.7638(7) A, and c =
      14.6289(6) A at 90(2) K with Z = 4. Refinement of 6123 reflections with 209
      parameters and no restraints yielded wR2 = 0.094 and R = 0.036 for 4042
      reflections with I > 2 sigma(I). The odd electron compound PdII(OEB.) has also
      been isolated and characterized by single-crystal X-ray diffraction. Black
      PdII(OEB.) crystallizes in the monoclinic space group I2/a with a = 13.274(3) A,
      b = 18.655(4) A, c = 14.114(3) A, and beta = 116.00(3) degrees at 140(2) K with Z
      = 4. Refinement of 2030 reflections with 195 parameters and no restraints yielded
      wR2 = 0.090 and R = 0.042 for 1715 reflections with I > 2 sigma(I). The structure
      again involves helical coordination of the linear tetrapyrrole to the palladium
      through the four pyrrole nitrogen atoms. Reduction of the complex causes a slight
      elongation of the Pd-N bonds from 1.983(2) and 1.986(2) A in [PdII(OEBOx)]I3 to
      2.011(4) and 2.012(4) A in PdII(OEB.).

PMID- 12526402
TI  - Spin frustration in MII[C(CN)3]2 (M = V, Cr). A magnetism and neutron diffraction
      study.
AB  - Three-dimensional coordination network solids of MII[C(CN)3]2 (M = V, Cr)
      composition possess interpenetrating rutile-like network structures. Each
      [C(CN)3]- bonds to three different metal ions in a triangular array, affording a
      geometrical topology akin to a Kagome lattice leading to competing spin exchange
      interactions and spin frustration. The crystal and magnetic structure of
      CrII[C(CN)3] was determined by Rietveld refinement of the powder neutron
      diffraction data at 2 and 15 K and belongs to the orthorhombic space group Pmna
      [a = 7.313(1) A, b = 5.453(1) A, c = 10.640(1) A, Z = 2, T = 15 K]. Each CrII has
      a tetragonally elongated octahedral structure with four Cr-N(1) distances of
      2.077(2) A and two significantly longer axial Cr-N(2) distances of 2.452(2) A.
      Magnetic susceptibility measurements between 1.7 and 300 K reveal strong
      antiferromagnetic interactions for both V- and Cr[C(CN)3]2 with theta = -67 and 
      46 K, respectively, from a fit to the Curie-Weiss law. Long-range magnetic
      ordering does not occur for M = V above 1.7 K, in contrast to M = Cr, which
      antiferromagnetically orders at low temperature. This is attributed to Jahn
      Teller distorted CrII site relieving frustration in one dimension, leading to 2-D
      Ising antiferromagnetism, as observed by both magnetic susceptibility and
      specific heat studies. Neutron diffraction experiments at 2 K for Cr[C(CN)3]2
      yielded additional Bragg reflections as a result of antiferromagnetic ordering
      with the moments on the CrII atoms aligned parallel to c and 4.7(1) microB.
      Fitting of the magnetic order parameter to a power law yielded TN = 6.12(4) K and
      beta = 0.18(1) consistent with 2-D Ising behavior. A TN of 6.13 K is also
      observed from the specific heat data.

PMID- 12526403
TI  - A new bimetallic assembly magnet [[Ni(tn)2]5[FeIII(CN)6]3]n(ClO4)n.2.5nH2O (tn =
      trimethylenediamine) with a novel 3-D tunnel structure.
AB  - A novel molecular-based magnet of three-dimensional (3-D) cyanide-bridged
      bimetallic assembly, [[Ni(tn)2]5[FeII(CN)6]3]n(ClO4)n.2.5nH2O where tn =
      trimethylenediamine, was synthesized and structurally characterized. The compound
      with an asymmetric unit of C24H52.5Cl0.5Fe1.5N19Ni2.5O3.255 crystallized in the
      monoclinic system of the space group P2(1)/n with a = 10.173(3) A, b = 16.053(2)
      A, c = 26.309(3) A, beta = 91.30(2) degrees, and Z = 4. The assembly has a 3-D
      network structure extended by three different types of FeIII-CN-NiII-NC-FeIII
      linkages. The iron (FeIII) atoms are located in two different chemical
      environments, which were confirmed by Mossbauer experimental results. The nickel
      (NiII) atoms have three different coordination environments. Cryomagnetic
      properties revealed that 3-D magnetic ordering occurs over the lattice below the
      Curie temperature around 10 K.

PMID- 12526404
TI  - Oligomerization of early transition metal [M(OH)3]2(mu-C2) acetylides toward the
      formation of [(OH)3MC]n (n = 4, 6) metalla carbides: a theoretical study by
      density functional theory.
AB  - Density functional calculations were performed on a series of M(OH3)-substituted
      (M = Ti,V) cyclopolyenes as simple models is metal carbides. We studied the
      oligomerization of the metal acetylide complexes [MLn]2 (mu-C2) as a possible
      precursor of these [(OH)3MC]n (n = 4,6) hypothetical species. Special emphasis
      was placed on the comparison of the main properties of these metal substituted
      cyclopolyenes with those of the corresponding cyclopolyenes in an attempt to
      study the effects of the metal substituents on the organic C4 and C6 cyclic
      moieties. Whereas for the titanium species, the pi system of the polyene moiety
      is slightly perturbed, the electronic structures and molecular geometries found
      for the vanadium species suggest a metalla radialene nature for these compounds,
      with the endocyclic conjugation of carbon-carbon double bonds replaced by an
      exocyclic arrangement of carbon-metal double bonds.

PMID- 12526405
TI  - Pd(II) complexes with polydentate nitrogen ligands. Molecular recognition and
      dynamic behavior involving Pd-N bond rupture. X-ray molecular structures of
      [[Pd(C6HF4)2](bpzpm)] and [[Pd(eta 3-C4H7)]2(bpzpm)] (CF3SO3)2 [bpzpm = 4,6
      bis(pyrazol-1-yl)pyrimidine].
AB  - The ligands 4,6-bis(pyrazol-1-yl)pyrimidine (bpzpm) and 4,6-bis(4-methylpyrazol-1
      yl)pyrimidine (Me-bpzpm) were synthesized and their reactions with some palladium
      derivatives explored. Mononuclear or dinuclear neutral or cationic complexes were
      obtained by reaction of the ligands with 1 or 2 equiv of Pd(C6XF4)2(cod) (cod =
      1,5-cyclooctadiene; X = F, H) or the palladium fragment [Pd(eta 3-2-Me
      C3H4)(S)2]+ (S = acetone). The reaction of the dinuclear derivatives with 1 equiv
      of the respective free ligand immediately led to the regeneration of the
      mononuclear complexes. Except in the case of the synthesis of
      [[Pd(C6HF4)2][Pd(C6F5)2](bpzpm)], where two similar metallic groups are present,
      all attempts to obtain dinuclear asymmetric complexes with two different
      palladium fragments failed. Instead, the dinuclear symmetric complexes were
      formed. This result could be considered as an example of molecular recognition
      with the ligand acting as a ditopic receptor. This behavior is comparable to
      chemical symbiosis but in this case applied to the ligand rather than to the
      metal center as occurs normally. The polyfluorophenyl rings are situated on
      average in a perpendicular orientation with respect to the coordination plane.
      Their restricted rotation results in several atropoisomers for the complexes with
      m-C6HF4. Different cross-reaction experiments were carried out, and these showed
      the mobility of the metallic fragments, with the more difficult process being
      that involving the more strongly bonded polyfluorophenyl palladium groups. By
      means of 1H NMR variable temperature studies, the interconversion of the two
      isomers of [[Pd(eta 3-C4H7)]2-(bpzpm)]Tf2 (Tf = CF3SO3) was analyzed. In the case
      of [[Pd(eta 3-C4H7)](bpzpm)]Tf the existence of two processes, an intramolecular
      apparent allyl rotation and an intermolecular exchange of the allylpalladium
      fragments, has been demonstrated. Different delta Gc++ values at the coalescence
      temperatures have also been determined. An X-ray single-crystal analysis was
      carried out on [[Pd(eta 3-C4H7)]2(bpzpm)]Tf2, which crystallizes in the
      monoclinic system, space group I2/m, with a = 9.368(2), b = 16.191(3), c =
      20.228(6) A, beta = 101.26(3), and Z = 4. Compound [[Pd(C6HF4)2](bpzpm)]
      crystallized in the triclinic system, space group P1, with a = 8.845(6), b =
      12.6609(9), c = 12.826(3) A, alpha = 88.45(2), beta = 74.36(3), gamma = 89.32(2),
      and Z = 2.

PMID- 12526406
TI  - A study of the sequential acid-catalyzed hydroxylation of dodecahydro-closo
      dodecaborate(2-).
AB  - The closo-[B12H12-n(OH)n]2- (n = 1-4) ions have been synthesized by the reaction
      of cesium dodecahydro-closo-dodecaborate(2-), Cs21, with aqueous sulfuric acid.
      Variation of the reaction temperature, time, and acid concentration results in
      the stepwise introduction of from one to four hydroxyl groups. Each individual
      hydroxylation step proceeds regioselectively, affording only one isomer per step.
      Further substitution of the hydroxylated cluster preferentially takes place at a
      B-H vertex meta to a B-OH vertex. The closo-[B12H12-n(OH)n]2- (n = 1-4) species,
      designated 2-5, respectively, are characterized by one- and two-dimensional 11B
      NMR spectroscopy, IR spectroscopy, and high-resolution fast atom bombardment
      (FAB) mass spectrometry. A rationale that qualitatively explains the influence of
      the hydroxyl group on the chemical shifts of the individual boron vertices is
      developed. Furthermore, the solid state structures of closo-[B12H11(OH)]2-, 2,
      and closo-1,7-[B12H10(OH)2]2-,3, are determined by X-ray diffraction.
      Crystallographic data are as follows: For [MePPh3](2)2, monoclinic, space group
      P2(1)/n, a = 890.1(5) pm, b = 1814(1) pm, c = 1270.5(7) pm, beta = 101.66(2)
      degrees, Z = 2, R = 0.055; for [MePPh3](2)3, monoclinic, space group P2(1)/n, a =
      887.6(4) pm, b = 1847.2(8) pm, c = 1271.1(5) pm, beta = 101.17(1) degrees, Z = 2,
      R = 0.065. In addition, synthetic routes to O-derivatized species of the anions 2
      5 such as closo-[B12H11(OTiCpCl2)]2-, 7, closo-1,7-[B12H10(OTiCpCl2)2]2-, 8,
      closo-1,7,9-[B12H9(OTiCpCl2)3]2-, 9, closo-[B12H11(OCONHPh)]2-, 10, and closo-1,7
      [B12H10(OSO2Me)2]2-, 11, are described. The crystal structures of 7 and 11 are
      determined by single-crystal X-ray diffraction. Crystallographic data are as
      follows: For [MePPh3](2)7, monoclinic, space group Cc, a = 2530.5(2) pm, b =
      1653.3(1) pm, c = 1281.3(1) pm, beta = 118.79(2) degrees, Z = 4, R = 0.085; for
      [HPy](2)11, monoclinic, space group P2(1)/n, a = 1550.9(8) pm, b = 993.1(5) pm, c
      = 1726.5(9) pm, beta = 112.36(2) degrees, Z = 4, R = 0.061.

PMID- 12526407
TI  - Kinetics and mechanism of copper(II) complex formation with tripodal
      aminopolythiaether and aminopolypyridyl ligands in aqueous solution.
AB  - The complex formation kinetics of aquated copper(II) ion reacting with 12 related
      tripodal ligands have been studied in aqueous solution at 25 degrees C, mu = 0.10
      M (NaClO4). For most of the ligands studied, specific formation rate constants
      have been resolved for both the unprotonated and monoprotonated ligand species.
      All of the tripodal ligands included in this study contain a bridgehead amine
      nitrogen with the three legs consisting of 2-methylthioethyl or 2-ethylthioethyl
      and/or 2-pyridylethyl or 2-pyridylmethyl. Since the bridgehead nitrogen is too
      sterically hindered to participate in initial coordinate bond formation, the
      first bond must involve a thiaether sulfur or a pyridine nitrogen on one of the
      pendant legs followed by coordination to the bridgehead nitrogen to complete the
      first chelate ring. All kinetic data are interpreted in terms of this presumed
      sequence in the bond formation steps. For the two ligands in which all three
      pendant legs contain thiaether sulfur donor atoms, the rate-determining step
      appears to be at the point of second bond formation (chelate ring closure),
      although the distinction is not well defined. For all other unprotonated ligands,
      the kinetic behavior is consistent with the first-bond formation being rate
      determining. Upon protonation, the rate-determining step appears to shift to the
      point of proton loss associated with second-bond formation in several cases. A
      particularly interesting observation is that the tripodal ligand
      tris(ethylthioethyl)amine (TEMEA) exhibits specific Cu(II) complex formation rate
      constants that are virtually identical to those for a closely related macrocyclic
      ligand, 1,4,8-trithia-11-azacyclotetradecane ([14]aneNS3), but the calculated
      CuIIL dissociation rate constants differ by a factor of 1000. A further
      comparison of the calculated dissociation rate constants for Cu(II)-tripodal
      ligand complexes indicates that a Cu(II)-N(pyridine) bond is approximately 10(4)
      times stronger than a Cu(II)-SR2 bond. This leads to the conclusion that a 1:1
      Cu(II)-SR2 complex would have a predicted stability constant of about 0.04 M-1 in
      aqueous solution--the first estimate obtained for the strength of a single Cu(II)
      S(thiaether) bond.

PMID- 12526408
TI  - Coordination of two high-affinity hexamer peptides to copper(II) and
      palladium(II) models of the peptide-metal chelation site on IMAC resins.
AB  - The coordination of peptides Ser-Pro-His-His-Gly-Gly (SPHHGG) and (His)6 (HHHHHH)
      to [PdII(mida)(D2O)] (mida2- = N-methyliminodiacetate) was studied by 1H NMR as
      model reactions for CuII(iminodiacetate)-immobilized metal affinity
      chromatography (IMAC) sites. This is the first direct physical description of
      peptide coordination for IMAC. A three-site coordination is observed which
      involves the first, third, and fourth residues along the peptide chain. The
      presence of proline in position 2 of SPHHGG achieves the best molecular mechanics
      and bonding angles in the coordinated peptide and enhances the interaction of the
      serine amino nitrogen. Histidine coordination of H1, H3, and H4 of (His)6 and H3
      and H4 of SPHHGG was detected by 1H NMR contact shifts and H/D exchange of
      histidyl protons. The EPR spectra of SPHHGG and HHHHHH attached to the
      [CuII(mida)] unit were obtained for additional modeling of IMAC sites. EPR
      parameters of the parent [Cu(mida)(H2O)2] complex are representative: gzz = 2.31;
      gyy = 2.086; gxx = 2.053; A parallel = 161G; AN = 19G (three line, one N
      coupling). Increased rhombic distortion is detected relative to the starting aqua
      complex in the order of [Cu(mida)L] for distortion of HHHHHH > SPHHGG > (H2O)2.
      The lowering of symmetry is also seen in the decrease in the N-shf coupling,
      presumably to the imino nitrogen of mida2- in the order 19 G (H2O), 16 G (SPHHGG)
      and 11 G (HHHHHH). Visible spectra of the [Cu(mida)(SPHHGG)] and
      [Cu(mida)(HHHHHH)] as a function of pH indicate coordination of one histidyl
      donor at ca. 4.5, two in the range of pH 5-7, and two chelate ring attachments
      involving the terminal amino donor for SPHHGG or another histidyl donor of HHHHHH
      in the pH domain of 7-8 in agreement with the [PdII(mida)L] derivatives which
      form the two-chelate-ring attachment even at lower pH as shown by the 1H NMR
      methods.

PMID- 12526409
TI  - Structural studies on layered alkylpyridinium iodopalladate networks.
AB  - The reaction of alkylpyridinium (CnH2n + 1NC5H5, hereafter Cn-Py) iodide salts in
      aqueous acetonitrile with a preformed palladium iodide precursor afforded two
      different types of organic-inorganic phases depending on the molar ratio. A 2:1
      ratio yielded the phase [Cn-Py]2[PdI4] (3, n = 14, 16), which crystallized in the
      triclinic crystal system. The X-ray crystal structure of 3, (n = 14), refined in
      the space group P1 (a = 8.918(3) A, b = 9.894(3) A, c = 29.062(12) A, alpha =
      93.51(3) degrees, beta = 94.17(3) degrees, gamma = 115.60(3) degrees, and Z = 2),
      consists of interdigitated bilayers with a basal spacing of 29.0 A. The aliphatic
      chains of the cations, which run almost parallel to the stacking direction, are
      fully stretched between polar planes built on isolated [PdI4]2- anions and cation
      headgroups. Changing the organic cation to palladium ratio to 1:1 led to a new
      phase [Cn-Py]2[Pd2I6] (4, n = 14, 16), which crystallizes in the triclinic P1
      space group (a = 9.399(4) A, b = 14.264(6) A, c = 29.415(13) A, alpha = 92.11(4)
      degrees, beta = 90.07(4) degrees, gamma = 104.53(3) degrees, Z = 3 for 4(n = 14);
      a = 9.417(2) A, b = 14.215(3) A, c = 31.552(6) A, alpha = 87.96(3) degrees, beta
      = 87.63(3) degrees, gamma = 75.67(3) degrees, Z = 3 for 4(n = 16)). The layered
      structure is basically of a continuously interdigitated single-layer type, with a
      bilayer sublattice superimposed. Isolated [Pd2I6]2- anions contribute to the
      inorganic planes. A high degree of interdigitation and tilting of the aliphatic
      chains lead to basal spacings of 29.4 and 31.5 A for 4(n = 14) and 4(n = 16),
      respectively. The [Cn-Py]2[PdI4] and [Cn-Py]2[Pd2I6] phases were characterized by
      thermal analysis. Mesomorphic behavior was observed only for 3(n = 16), which was
      confirmed by variable-temperature powder XRD and optical microscopy.

PMID- 12526410
TI  - Reaction of CF3 radicals with CO and O2. Isolation of
      bis(trifluoromethyl)peroxydicarbonate, CF3OC(O)OOC(O)OCF3, and identification of
      bis(trifluoromethyl)trioxydicarbonate, CF3OC(O)OOOC(O)OCF3.
AB  - The synthesis of CF3OC(O)OOCF3, CF3OC(O)OOC(O)OCF3, and CF3OC(O)OOOC(O)OCF3 is
      accomplished by the photolysis of a mixture of (CF3CO)2O, CO, and O2. Pure
      CF3OC(O)OOCF3 and CF3OC(O)OOC(O)OCF3 are isolated after thermal decomposition of
      CF3OC(O)OOOC(O)OCF3 and repeated trap-to-trap condensation. Additional
      spectroscopic data of known CF3OC(O)OOCF3 are obtained by recording NMR, IR,
      Raman, and UV spectra: At room temperature CF3OC(O)OOC(O)OCF3 is stable for days
      in the liquid or gaseous state. The melting point is -38 degrees C, and the
      boiling point is extrapolated to 73 degrees C from the vapor pressure curve log p
      = 8.657-1958/T (p/mbar, T/K). The new compound is characterized by molecular mass
      determination and by NMR, vibrational, and UV spectroscopy. The new trioxide
      CF3OC(O)OOOC(O)OCF3 cannot be separated from CF3-OC(O)OOC(O)OCF3 by distillation
      due to their similar boiling points. CF3OC(O)OOOC(O)OCF3 decomposes at room
      temperature within hours into a mixture of CF3OC(O)OOC(O)OCF3, CF3OC(O)OOCF3,
      CO2, and O2. Its characterization is discussed along with a possible mechanism
      for formation and decomposition reactions.

PMID- 12526411
TI  - Electron transfer. 141. Reactions of indium(I) with transition metal center
      oxidants.
AB  - Aqueous solutions of the hypovalent state In(I) reduce a series of complexes of
      Fe(III) and selected derivatives of Ir(IV), Cr(V), Pt(IV), Ag(III), and Ni(IV).
      All reactions yield In(III). Ions derived from Fe(III) and Ir(IV) undergo net le-
      conversions, whereas the other oxidants change by two units. Reductions of
      Fe(III) are strongly promoted by increasing pH or by adding Cl-, Br-, NCS-, or N3
      . Reaction appears to proceed through monoligated complexes, FeIII(Lig-)2+, and
      the kinetic response to alteration of added ligand indicates initiation mainly
      via a bridged transition state FeIII-Lig-InI. Oxidations by Fe(CN)6(3-) are
      exceptionally rapid, those by FeIII(EDTA) are unusually slow, and redox is
      blocked by addition of excess F-. Reduction of IrCl6(2-) proceeds somewhat more
      slowly than predicted by the marcus model for outer-sphere reactions. Conversions
      of the 2e- oxidants are rapid. For these, multistep routes initiated by le-
      changes are reasonable, but direct 2e-paths involving oxygen transfer (from CrVO)
      or Cl+ transfer (from PtCl6(2-)) cannot be ruled out. Whether inner-sphere 2e-
      transactions without transfer of atomic species can be competitive remains an
      open question.

PMID- 12526412
TI  - Matrix infrared spectroscopic study of magnesium carbene and carbenoid radicals
      and analysis of their bonding with density functional calculations.
AB  - Magnesium atoms generated by laser ablation were reacted with methyl halides and
      methane diluted in argon. Among the reaction products were the metal carbene
      species, MgCH2, and carbenoid radicals, XMgCH2 (where X = H, F, Cl, and Br). This
      investigation reports matrix infrared spectra for Mg carbene and carbenoid
      species in a cold matrix, and electronic structure calculations for these and
      related beryllium species. An unusual bonding interaction for the MCH2 species is
      described in which the bonding in the alpha and beta manifolds is qualitatively
      different. Vibrational frequencies and analysis of the results of density
      functional calculations provide information about the nature of the bonding in
      these species and allow for a comparison to the well-known transition metal
      Fischer- and Schrock-type carbene complexes. The special difficulties of
      computational modeling of vibrations in highly polar molecules are discussed.

PMID- 12526413
TI  - Syntheses, structures, and properties of the bis(cyclopentadienyl) rare-earth
      imidodiphosphinochalocogenido compounds Cp2Ln[N(QPPh2)2] (Ln = La, Gd, Er, or Yb
      for Q = Se; Ln = Yb for Q = S).
AB  - The compounds Cp2Ln[N(QPPh2)2] (Ln = La (1), Gd (2), Er (3), or Yb (4) for Q =
      Se, Ln = Yb (5) for Q = S) have been synthesized from the corresponding rare
      earth tris(cyclopentadienyl) compound and H[N(QPPh2)2]. The structures of
      compounds 1, 2, 3, and 5, as determined by X-ray crystallography, consist of a
      Cp2Ln fragment, coordinated eta 3 through two chalcogen atoms and an N atom of
      the imidodiphosphinochalcogenido ligand [N(QPPh2)2]-. In compound 4, the Cp2Yb
      moiety is coordinated eta 2 through the two Se atoms of the [N(SePPh2)2]-ligand.
      31P and 77Se (for 1) NMR spectroscopies lend insight into the solution nature of
      these species. Crystal data: 1, C34H30LaNP2Se2, triclinic, P1, a = 9.7959(10) A,
      b = 12.4134(13) A, c = 13.9077(14) A, alpha = 88.106(2) degrees, beta = 88.327(2)
      degrees, gamma = 68.481(2) degrees, V = 1572.2(3) A3, T = 153 K, Z = 2, and R1(F)
      = 0.0257 for the 5947 reflections with I > .2 sigma(I); 2, C34H30GdNP2Se2,
      triclinic, P1, a = 9.7130(14) A, b = 12.2659(17) A, c = 13.953(2) A, alpha =
      88.062(2) degrees, beta = 87.613(2) degrees, gamma = 69.041(2) degrees, V =
      1550.7(4) A3, T = 153 K, Z = 2, and R1(F) = 0.0323 for the 5064 reflections with
      I > 2 sigma(I); 3, C34H30ErNP2Se2, triclinic, P1, a = 9.704(2) A, b = 12.222(3)
      A, c = 13.980(4) A, alpha = 88.230(4) degrees, beta = 87.487(4) degees, gamma =
      69.107(4) degrees, V = 1547.4(7) A3, T = 153 K, Z = 2, and R1(F) = 0.0278 for the
      6377 reflections with I > 2 sigma(I); 4, C34H30NP2Se2Yb.C4H8O, triclinic, P1, a =
      12.087(4) A, b = 12.429(4) A, c = 23.990(7) A, alpha = 89.406(5) degrees, beta =
      86.368(5) degrees, gamma = 81.664(5) degrees, V = 3558.8(18) A3, T = 153 K, Z =
      4, and R1(F) = 0.0321 for the 11,883 reflections with I > 2 sigma(I); and 5,
      C34H30NP2S2Yb, monoclinic, P21/n, a = 13.8799(18) A, b = 12.6747(16) A, c =
      17.180(2) A, beta = 91.102(3) degrees, V = 3021.8(7) A3, T = 153 K, Z = 4, and
      R1(F) = 0.0218 for the 6698 reflections with I > 2 sigma(I).

PMID- 12526414
TI  - Soluble yttrium chalcogenides: syntheses, structures, and NMR properties of Y[eta
      3-N(SPPh2)2]3 and Y[eta 2-N(SePPh2)2]2[eta 3-N(SePPh2)2].
AB  - The compounds Y[N(QPPh2)2]3 (Q = S (1), Se (2)) have been synthesized in good
      yield from the protonolysis reactions between Y[N(SiMe3)2]3 and HN(QPPh2)2 in
      methylene chloride (CH2Cl2). The compounds are not isostructural. In 1, the Y
      atom is surrounded by three similar [N(SPPh2)2]- ligands bound eta 3 through two
      S atoms and an N atom. The molecule possesses D3 symmetry, as determined in the
      solid state by X-ray crystallography and in solution by 89Y and 31P NMR
      spectroscopies. In 2, the Y atom is surrounded again by three [N(SePPh2)2]-
      ligands, but two are bound eta 2 through the two Se atoms and the other ligand is
      bound eta 3 through the two Se atoms and an N atom. Although a fluxional process
      is detected in the 31P and 77Se NMR spectra, a triplet is found in the 89Y NMR
      spectrum of 2 (delta = 436 ppm relative to YCl3 in D2O, 2JY-P = 5 Hz). This
      implies that on average the conformation of one eta 3- and two eta 2-bound
      ligands is retained in solution. Crystallographic data for 1: C72H60N3P6S6Y,
      rhombohedral, R3c, a = 14.927(5) A, c = 56.047(13) A, V = 10815(6) A3, T = 153 K,
      Z = 6, and R1(F) = 0.042 for the 1451 reflections with I > 2 sigma(I).
      Crystallographic data for 2: C72H60N3P6Se6Y.Ch2-Cl2, monoclinic, P2(1)n, a =
      13.3511(17) A, b = 38.539(7) A, c = 14.108(2) A, beta = 94.085(13) degrees, V =
      7241(2) A 3, T = 153 K, Z = 4, and R1(F) = 0.037 for the 8868 reflections with I
      > 2 sigma(I).

PMID- 12526415
TI  - Organoantimony(V) cyanoximates: synthesis, spectra and crystal structures.
AB  - A series of 25 new organoantimony(V) cyanoximates has been synthesized and
      studied using IR, visible, and NMR spectroscopy and X-ray analysis. Crystal
      structures were determined for compounds (C6H5)4Sb[ONC(CN)C(O)NH2] (1) and
      (C6H5)4Sb[ONC(CN)C(O)N(CH3)2] (2). Both complexes crystallized in the monoclinic
      space group P2(1)/c (Z = 4) with unit cell parameters (A, grad) of a = 14.921(3),
      b = 10.165(2), c = 17.571(7), beta = 113.26(6) for compound 1, and a = 16.415(4),
      b = 10.406(3), c = 17.152(3), beta = 17.152(3), beta = 117.79(2) for compound 2.
      For 5438 and 5056 independent reflections the refinement yielded R-factors 0.022
      and 0.037 for the structures of 1 and 2, respectively. Cyanoxime anions are bound
      to the antimony(V) atoms in a monodentate fashion via the oxygen atoms of the
      oxime groups. The ligands adopt trans-anti configuration in these compounds. The
      coordination polyhedron in both complexes is a distorted trigonal bipyramid with
      the axial location of the cyanoxime ligand. A similar binding mode of other
      anions in synthesized organoantimony(V) complexes has been offered on the basis
      of the similarity of their IR spectra to those of the compounds whose structures
      were determined crystallographically. The exact assignment of vibrations
      involving the oxime group was carried out using synthesized 15N(53%),
      isotopomers.

PMID- 12526416
TI  - Alkali salts of C3-symmetric, linked aryloxides: selective binding of substrates
      with metal aggregates.
AB  - The lithium, sodium, and potassium salts of tris(3,5-dialkyl-2
      hydroxyphenyl)methanes (tert-butyl, tert-pentyl, methyl) have been prepared by
      reaction of the triarylmethane with n-butyllithium, sodium hydride, and potassium
      hydride, respectively. These compounds are all hexanuclear aggregates composed of
      two triarylmethane units. Whereas the lithium salt is compact and cannot bind
      oxygen-donor solvent molecules, the sodium and potassium systems have vacant
      coordination sites that can interact with solvents. For the sodium compounds, the
      solvent can be subsequently removed, and the resulting coordinatively unsaturated
      compounds have been shown to selectively bind oxygen-donor substrates (ethers,
      aldehydes, and ketones) of suitable size and shape. The paper reports the
      synthesis and characterization of these novel compounds, including thirteen
      crystal structures of the salts and their adducts.

PMID- 12526417
TI  - Variable-energy photoelectron spectroscopy of substituted rhenium and manganese
      pentacarbonyls: molecular orbital assignments and the interatomic resonant
      effect.
AB  - High-resolution variable-energy photoelectron spectra of M(CO)5X [M = Re, X =
      Re(CO)5, Cl, Br, and I; and M = Mn, X = Mn(CO)5 and Br] are reported. Tunable
      synchrotron radiation is used to distinguish the Re 5d and Br 4p orbital based
      peaks for the controversial Re(CO)5Br. Our results provide firm molecular orbital
      assignments for all of these molecules. The valence orbital in the ordering of
      ionization energies for M(CO)5Cl (M = Mn and Re) and Mn(CO)5Br is a 1(M-X) > e(X)
      > b2(M) > e(M); but for M(CO)5I (M = Mn and Re) and Re(CO)5Br the ordering is
      a1(M-X) > e(M) > b2(M) > e(X). The crossover of the HOMO in the Re molecules due
      to the change in the halogen electronegativities occurs at Re(CO)5Br. The metal
      np-->nd resonance is observed for all of these molecules. For molecules like
      M2(CO)10 (M = Re and Mn) and Mn(CO)5Br, the observation of this np-->nd resonance
      is useful in assigning the metal nd based orbitals in their valence level
      spectra. However, for molecules like Re(CO)5X (X = Br and Cl), a np-->nd type
      resonance is observed on bands arising from both Re 5d and halogen mp based
      orbitals. This new resonant effect on the ligand-based orbitals is shown to be
      mainly due to the interatomic resonant effect. The core and valence level
      chemical shifts of these compounds are treated using Jolly's approach to confirm
      the assignments for the valence level spectra of some of these molecules. The
      high-resolution inner valence and core level spectra of these compounds are
      reported. Broadening of Re 4f, Br 3d, and I 4d core level spectra is discussed.
      The Auger peaks are observed in the high-resolution, high-intensity Br 3d of
      Re(CO)5Br and I 4d of Re(CO)5I spectra.

PMID- 12526418
TI  - Mixed uranium chloride fluorides UF6-nCln and methoxyuranium fluorides UF6
      n(OCH3)n: a theoretical study of equilibrium geometries, vibrational frequencies,
      and the role of the f orbitals.
AB  - The title compounds, the uranium (VI) fluoride chlorides (UF6-nCln, n = 0-6) and
      methoxyuranium (VI) fluorides [UF6-n(OCH3)n, n = 0-5], have been studied using
      relativistic density functional theory. Applying the B3LYP hybrid functional and
      an effective core potential on uranium, equilibrium geometries have been
      calculated for these molecules. In addition, harmonic vibrational frequencies
      have been computed for the chloride fluorides. Calculated frequencies have been
      compared to experiment where possible. All experimentally observed bands have
      been assigned, based on these calculations. The average deviation between
      theoretical and experimental frequencies is 15.6 cm-1 for 23 experimental modes.
      Theory always underestimates the experimental frequencies. This can be explained
      by the calculated bond lengths that are somewhat too long. The electronic
      structure of the uranium (VI) chloride fluorides has been investigated using
      scalar relativistic calculations and the PW91 functional. Periodic trends in the
      role and bonding contribution of the uranium 5f orbitals are discussed.

PMID- 12526419
TI  - Synthesis and structures of bis(dithiolene)-tungsten(IV) complexes related to the
      active sites of tungstoenzymes.
AB  - Recent protein crystallographic results on tungsten enzymes and primary sequence
      relationships between certain molybdenum and tungsten enzymes provoke interest in
      the generalized bis(dithiolene) complexes [WIV(QR)(S2C2R'2)2]1- and
      [WVIO(QR)(S2C2R'2)2]1- (Q = O, S, Se) as minimal representations of enzyme sites.
      The existence and stability of W(IV) complexes have been explored by synthesis.
      Reaction of [W(CO)2(S2C2Me2)2] (1) with PhO- results in complete CO substitution
      to give [W(OPh)(S2C2Me2)2]1- (2). Reaction of 1 with PhQ- affords the
      monocarbonyls [W(CO)(QPh)(S2C2Me2)2]1- (Q = S (3), Se (5)). The use of sterically
      demanding 2,4,6-Pri3C6H2Q- also yields monocarbonyls, [W(CO)(QC6H2-2,4,6
      Pri3)(S2C2Me2)2]1- (Q = S (4), Se (6)). The X-ray structures of square pyramidal
      2 and trigonal prismatic 3-6 (with unidentate ligands cis) are described. The
      tendency to substitute one or both carbonyl ligands in 1 in the formation of
      [MIV(QAr)(S2C2Me2)2]1- and [MIV(CO)(QAr)(SeC2Me2)2]1- with M = Mo and W is
      related to the M-Q bond length and ligand steric demands. The results demonstrate
      a stronger binding of CO by W(IV) than Mo(IV), a behavior previously demonstrated
      by thermodynamic and kinetic features of zerovalent carbonyl complexes. Complexes
      3-6 can be reversibly reduced to W(III) at approximately -1.5 V versus SCE. On
      the basis of the potential for 2(-2.07 V), monocarbonyl ligation stabilizes
      W(III) by approximately 500 mV. This work is part of a parallel investigation of
      the chemistry of bis(dithiolene)-molybdenum (Lim, B. S.; Donahue, J. P.; Holm, R.
      H. Inorg. Chem. 2000, 39, 263) and -tungsten complexes related to enzyme active
      sites.

PMID- 12526420
TI  - Synthesis of halogenated polyhedral phosphaboranes. Crystal structure of closo
      1,7-P2B10Cl10.
AB  - The 12-vertex closo-phosphaborane 1,7-P2B10Cl10 (1) has been prepared in low
      yield from the pyrolysis reaction of B2Cl4 with PCl3 at temperatures above 400
      degrees C. A single-crystal X-ray structure determination of 1 (monoclinic space
      group P2(1)/n with a = 9.239(2) A, b = 16.786(3) A, c = 15.739(3) a, beta =
      93.25(3) degrees, and Z = 4) confirmed that, consistent with its 26 skeletal
      electron count, the phosphaborane adopts a distorted icosahedral structure with
      the phosphorus atoms in the 1,7-positions. Crystals of 1 contain toluene in a 1:1
      molar ratio embedded between each P atom of neighboring cluster molecules.
      Alteration of the pyrolytic conditions resulted in the formation of the
      phosphaboranes P4B8Cl6 (2) and P2B8Cl8 (3), which were characterized
      spectroscopically. Copyrolysis of B2Cl4 with a mixture of PCl3 and AsCl3 at 450
      degrees C generated the six-vertex arsaphosphaborane AsPB4Cl4 (4) and traces of
      the icosahedral arsaphosphaborane AsPB10Cl10. These compounds are examples of
      heteroboranes which contain two different group-15 atoms within a single
      molecule.

PMID- 12526421
TI  - Metal-metal interactions as a function of bridging ligand topology: an
      electrochemical, spectroelectrochemical, and magnetic study on dinuclear Oxo
      Mo(V) complexes with various isomers of dihydroxynaphthalene as bridging ligand.
AB  - Reaction of [MoV(TpMe,Me)(O)Cl2] with 1,3-, 1,5-, 1,6-, 2,6-, and 2,7
      dihydroxynaphthalene affords the dinuclear complexes [[Mo(TpMe,Me)(O)Cl]2(mu
      C10H6O2)], abbreviated as 1,3-Mo2, 1,5-Mo2, 1,6-Mo2, 2,6-Mo2, and 2,7-Mo2,
      according to the substitution pattern of the bridging ligand. Electrochemical, UV
      vis/NIR spectroscopic, and variable-temperature magnetic susceptibility studies
      have been used to probe the effects of the bridging-ligand topology on the metal
      metal electronic and magnetic interactions. The complexes can be split into two
      classes according to the properties of the bridging ligands. Complexes 1,3-Mo2,
      1,6-Mo2, and 2,7-Mo2 all have bridging ligands that are topologically equivalent
      to meta-substituted bridging ligands such as 1,3-dihydroxybenzene, in that (i)
      there is an odd number of C atoms separating the two oxygen atoms, regardless of
      the pathway that is taken through the ligand skeleton, and (ii) the doubly
      oxidized from of the bridging ligand is a diradical. These complexes are
      classified as being "T-meta" (= topologically equivalent to meta). Complexes 1,5
      Mo2 and 2,6-Mo2 have bridging ligands that are topologically equivalent to para
      substituted groups such as 1,4-dihydroxybenzene, in that (i) there is an even
      number of C atoms separating the two oxygen atoms, whichever pathway is taken
      through the ligand skeleton, and (ii) the doubly oxidized form of the bridging
      ligand is a diamagnetic quinone. These complexes are classified as "T-para".
      Electrochemical studies show that the comproportionation constants for the
      Mo(V)/Mo(IV) mixed-valence states of the T-meta complexes are smaller than those
      for the T-para complexes. Spectroelectrochemical studies show that the
      Mo(V)/Mo(IV) mixed-valence states of the T-para complexes show pronounced Mo(IV)-
      >Mo(V) IVCT transitions, whereas those of the T-meta complexes do not show these
      transitions. Magnetic susceptibility studies show that the T-meta complexes all
      display ferromagnetic exchange between the metal centers, whereas the T-para
      complexes all display antiferromagnetic exchange. Thus, both the electronic and
      the magnetic properties of these complexes show a clear demarcation into two sets
      according to the bridging-ligand topology.

PMID- 12526422
TI  - Thermal and photochemical reduction of aqueous chlorine by ruthenium(II)
      polypyridyl complexes.
AB  - Studies are reported on the reactions of aqueous chlorine with a series of
      substitution-inert, one-electron metal-complex reductants, which includes
      [Ru(bpy)3]2+, [Ru(4,4'-Me2bpy)3]2+, [Ru(4,7-Me2phen)3]2+, [Ru(terpy)2]2+, and
      [Fe(3,4,7,8-Me4phen)3]2+. The reactions were studied by spectrophotometry at 25
      degrees C in acidic chloride media at mu = 0.3 M. In general the reactions have
      the stoichiometry 2[ML3]2+ + Cl2-->2[ML3]3+ + 2Cl-. In the case of [Ru(bpy)3]2+,
      the reaction is quite photosensitive; the thermal reaction is so slow as to be
      practically immeasurable. The reactions of [Ru(4,4'-Me2bpy)3]2+ and [Ru(4,7
      Me2phen)3]2+ are also highly photosensitive, giving pseudo-first-order rate
      constants that depend on the monochromator slit width in a stopped-flow
      instrument; however, the thermal rates are fast enough that they can be obtained
      by extrapolation of kobs to zero slit width. The reactions of [Ru(terpy)2]2+ and
      [Fe(3,4,7,8-Me4phen)3]2+ show no appreciable photosensitivity, allowing direct
      determination of their thermal rate laws. From the kinetic effects of pH,
      [Cl2]tot, and [Cl-] it is evident that all of the thermal rate laws have a first
      order dependence on [ML3]2+ and on [Cl2]. The second-order rate constants
      decrease as Eo for the complex increases, consistent with the predictions of
      Marcus theory for an outer-sphere electron-transfer mechanism. Quantum yields at
      460 nm for the reactions of [Ru(4,4'-Me2bpy)3]2+ and [Ru(4,7-Me2phen)3]2+ exceed
      0.1 and show a dependence on [Cl2] indicative of competition among spontaneous
      decay of *Ru, nonreactive quenching by Cl2, and reactive quenching by Cl2.

PMID- 12526423
TI  - Synthesis and reactivity of hydrazido(2-) and imido derivatives of titanium(IV)
      tetratolylporphyrin.
AB  - Titanium porphyrin hydrazido complexes (TTP)Ti = NNR2 (TTP = meso-tetra-p
      tolylporphyrinato dianion; R = Me (1), Ph (2)) were synthesized by treatment of
      (TTP)TiCl2 with 1,1-disubstituted hydrazines H2NNR2 (R = Me, Ph) in the presence
      of piperdine. The nucleophilic character of the hydrazido moiety was demonstrated
      in the reactions of complexes 1 and 2 with p-chlorobenzaldehyde, which yielded
      the titanium oxo complex (TTP)-Ti = O and the respective hydrazones. Protonation
      of complexes 1 and 2 with phenol or water produced the 1,1-disubstituted
      hydrazine along with (TTP)Ti(OPh)2 or (TTP)Ti = O, respectively. Similar
      reactivity of p-chlorobenzaldehyde and phenol with (TTP)Ti = NiPr, 3, was
      observed. The reaction of complex 3 with nitrosobenzene cleanly formed the azo
      compound iPrN = NPh and the terminal oxo product (TTP)Ti = O.

PMID- 12526425
TI  - Kinetics and mechanism of the monomerization of a Re(V) dithiolato dimer with
      monodentate ligands. Electronic and steric effects.
AB  - The sulfur-bridged dimeric dithiolato rhenium(V) chelate [CH3(O)Re(eta 2,mu-o
      SCH2C6H4S)]2 (D), derived from 2-mercaptothiophenol, was monomerized to give
      [CH3(O)Re(eta 2-o-SCH2C6H4S)]L (M-L) in benzene upon reaction with various
      neutral and anionic monodentate ligands (L) such as pyridine and its substituted
      derivatives, triarylphosphines, dimethyl sulfoxide, 4-picoline-N-oxide, and
      halide ions. The kinetic observations can readily be interpreted for all ligands
      by a unified mechanism in which the initial fast formation of a 1:1 (DL) and 1:2
      (DL2) adduct is followed by the slow monomerization of each species so formed.
      The use of different ligands gave insight into different steps of the same
      multistep mechanism. The kinetics of ligand exchange between free L and the
      monomeric complexes was also studied; an associative pathway has been proposed to
      interpret the results. The crystal structures of two new monomeric ML complexes
      (with L = 4-acetylpyridine and 1,3-diethylthiourea) are reported.

PMID- 12526424
TI  - Isomeric equilibria in aqueous solution involving aromatic ring stacking in the
      sexternary complexes formed by the quaternary cis-(NH3)2Pt(2'-deoxyguanosine
      N7)(dGMP-N7) complex and the binary Cu(2,2'-bipyridine)2+ or Cu(1,10
      phenanthroline)2+ complexes (dGMP2- = 2'-deoxyguanosine 5'-monophosphate).
AB  - To the best of our knowledge, for the first time the stabilities of sexternary
      complexes are determined by potentiometric pH titrations in aqueous solution at
      25 degrees C and I = 0.1 M (NaNO3). The sexternary complexes form by binding of
      the binary Cu(Arm)2+ complexes, where Arm = 2,2'-bipyridine (Bpy) or 1,10
      phenanthroline (Phen), to the -PO3(2-) group present in the quaternary cis
      (NH3)2Pt(dGuo)(dGMP) complex. It is shown by stability constant comparisons and
      spectrophotometric measurements (observation of charge-transfer bands for the
      Phen system) that the [cis-(NH3)2Pt(dGuo)(dGMP).Cu(Arm)]2+ complexes can fold in
      such a way that aromatic ring stacking between the aromatic rings of Bpy or Phen
      and a guanine residue (most probably the one of dGMP2-) becomes possible. The
      formation degree of the stacks reaches approximately 25 and 50% for the [cis
      (NH3)2Pt-(dGuo)(dGMP).Cu(Bpy)]2+ and [cis-(NH3)2Pt(dGuo)(dGMP).Cu(Phen)]2+
      species, respectively. By comparisons with Cu(Arm)(dGMP) complexes, it is shown
      that the cis-(NH3)2Pt2+ unit coordinated to N7 of the guanine residues in the
      sexternary complexes inhibits stacking but does not prevent it. This result is of
      general importance because it demonstrates that in aqueous solution purine
      residues of nucleotides or nucleic acids that carry a metal ion at N7 can still
      undergo stacking interactions with other suitable aromatic ring systems.

PMID- 12526426
TI  - Site-specific methylation of coordinated 1,2,4-triazoles: a novel route to
      sterically hindered Ru(bpy)2 complexes.

PMID- 12526427
TI  - A convenient route to synthesize the fully conjugated bimetallic complex
      (Bu4N)2[tto[Ni(dmit)2]] (tto = tetrathiooxalate, C2S4(2-), and dmit = 1,3
      dithiole-2-thione-4,5-dithiolate, C3S5(2-) and the crystal structure of a new
      crystal form.
AB  - A novel route for the conversion of (Bu4N)2[Ni(dmit)2] to (Bu4N)2[tto[Ni(dmit)2]]
      is reported here. This provides a much more efficient way of synthesizing
      (Bu4N)2[tto[Ni(dmit)2]] than the literature method. During the process, the
      conversion of dmit2- to tto2- was realized for the first time. This new synthesis
      should facilitate further research on the conducting bimetallic complexes
      [C]x[tto[Ni(dmit)2]]. In addition, a new crystal form of (Bu4N)2[tto[Ni(dmit)2]].
      In addition, a new crystal form of (Bu4N)2[tto[Ni(dmit)2]] was determined by X
      ray crystallographic analysis.

PMID- 12526428
TI  - Cuboidal W3S4 cluster complexes as new generation X-ray contrast agents.

PMID- 12526429
TI  - Solid state structures of [Ag5(dppm)4(S2CC(CN)P(O)(OEt)2)2][PF6] and
      Ag4(dppm)4(S2CC(CN)P(O)(OEt)2)2: variable coordination modes of 1,1-dithiolate to
      silver(I).

PMID- 12526430
TI  - Analogues of the Tp* ligand containing a 3-Me but non-methyl 5-R groups.

PMID- 12526431
TI  - Crystal structures of tris(8-dimethylaminonaphthyl)phosphane and its
      hydrochloride salt. The first seven-coordinate phosphorus compound.

PMID- 12526432
TI  - Synthesis and first X-ray structural analysis of monomeric imino-lambda 5
      stibanes.

PMID- 12526433
TI  - Molecular rectification by a bimetallic Ru-Os compound anchored to
      nanocrystalline TiO2.

PMID- 12526434
TI  - Self-assembly molecular squares with metal complexes as bridging ligands.

PMID- 12526435
TI  - Preparation and crystal structures of formato complexes of the [MIV3O4]4+ and
      [MIV3S4]4+ (M = Mo, W) clusters. Convenient precursors to the corresponding aqua
      complexes.
AB  - In the aqueous chemistry of molybdenum(IV) and tungsten(IV), trinuclear,
      incomplete cubane-like, oxo and sulfido clusters of the type [M3E4]4+ (M = Mo, W;
      E = O, S) play a central role. We here describe how formato complexes of all
      these cluster cores can be prepared in high yields by crystallization from
      methanol-water or ethanol-water mixtures. Since potassium and ammonium formate
      are very soluble in these alcohol-water mixtures, high formate concentrations
      could be accomplished in the solutions from which the corresponding salts of
      cluster formato complexes crystallized. The [Mo3O4]4+ compounds could be
      synthesized without requiring the use of noncomplexing acids in the process. Some
      [M3E4]4+ compounds were characterized by single-crystal structure determinations.
      [NH4]3.20[K]0.80[H3O][Mo3O4(HCO2)8][HCO2].H2O was triclinic, space group P1 (No.
      2) with a = 11.011(2) A, b = 13.310(2) A, c = 9.993(1) A, alpha = 106.817(7)
      degrees, beta = 91.651(9) degrees, gamma = 88.340(9) degrees, and two formula
      units per cell. [K]6[W3S4(HCO2)9][HCO2].2.27H2O.0.73CH3OH was monoclinic, space
      group C2/m (No. 12) with a = 19.605(6) A, b = 14.458(7) A, c = 13.627(5) A, beta
      = 118.94(2) degrees, and four formula units per cell. Generally, the nine
      coordination sites of [M3E4]4+ were occupied either by a mixture of monodentate
      and mu 2-bridging formato ligands or by monodentate formato ligands only. By
      dissolution in noncomplexing strong acid, all the formato complexes immediately
      hydrolyzed to form [M3E4(H2O)9]4+ aqua complexes. This allows, for example, high
      concentrations of [Mo3S4(H2O)9]4+ in CF3SO3H to be obtained and these solutions
      to be used for the synthesis of bimetallic clusters containing the cubane-like
      motif Mo3M'S4.

PMID- 12526436
TI  - Superexchange in magnetic insulators: an interpretation of the metal-metal charge
      transfer energy in the Anderson theory.
AB  - The superexchange interactions in four three-center model systems A-L-B, for A
      and B being paramagnetic centers and L a diamagnetic bridging ligand, are
      analyzed by valence bond configuration interaction models in combination with
      fourth-order perturbation theory. We analyze the four distinct cases where a
      bridging ligand orbital simultaneously interacts with half-filled orbitals
      localized on A and B (case i), a half-filled orbital localized on A and an empty
      orbital localized on B (case ii), a full orbital localized on A and a half-filled
      orbital localized on B (case iii), and finally a full orbital localized on A and
      an empty orbital localized on B (case iv). In all four cases we compare our new
      results using localized orbitals with the equivalent results obtained using the
      Anderson ansatz of delocalized (magnetic) orbitals. The effective metal-to-metal
      electron transfer energy Ueff in the old formalism with delocalized orbitals is
      expressed in terms of the metal-to-metal electron transfer energy U and the
      ligand-to-metal electron transfer energy delta using localized orbitals. We find
      that the old formalism containing only Ueff is in general not sufficient. For
      cases i and ii we show that Ueff can be regarded as an effective U strongly
      reduced with respect to the free ion as a result of hybridization effects,
      whereas the same reduction of U for the cases iii and iv is not possible. The
      relevance and applicability of our theoretical results is demonstrated on
      magnetochemical data from the literature.

PMID- 12526437
TI  - Ferromagnetism in malonato-bridged copper(II) complexes. Synthesis, crystal
      structures, and magnetic properties of [[Cu(H2O)3][Cu(mal)2(H2O)]]n and
      [[Cu(H2O)4]2[Cu(mal)2(H2O)]][Cu(mal)2(H2O)2][[Cu(H2O)4][Cu(mal)2(H2O)2][(H2mal =
      malonic acid).
AB  - Three malonato-bridged copper(II) complexes of the formulas
      [[Cu(H2O)3][Cu(C3H2O4)2(H2O)]]n (1), [[Cu(H2O)4]2[Cu(C3H2O4)2(H2O)]]
      [Cu(C3H2O4)2(H2O)2][[Cu(H2O)4][Cu(C3H2O4)2(H2O)2]] (2), and
      [Cu(H2O)4][Cu(C3H2O4)2(H2O)2] (3) (C3H2O4 = malonate dianion) have been prepared,
      and the structures of the two former have been solved by X-ray diffraction
      methods. The structure of compound 3 was already known. Complex 1 crystallizes in
      the orthorhombic space group Pcab, Z = 8, with unit cell parameters of a =
      10.339(1) A, b = 13.222(2) A, and c = 17.394(4) A. Complex 2 crystallizes in the
      monoclinic space group P2/c, Z = 4, with unit cell parameters of a = 21.100(4) A,
      b = 21.088(4) A, c = 14.007(2) A, and beta = 115.93(2) degrees. Complex 1 is a
      chain compound with a regular alternation of aquabis(malonato)copper(II) and
      triaquacopper(II) units developing along the z axis. The
      aquabis(malonato)copper(II) unit acts as a bridging ligand through two slightly
      different trans-carboxylato groups exhibiting an anti-syn coordination mode. The
      four carboxylate oxygens, in the basal plane, and the one water molecule, in the
      apical position, describe a distorted square pyramid around Cu1, whereas the same
      metal surroundings are observed around Cu2 but with three water molecules and one
      carboxylate oxygen building the equatorial plane and a carboxylate oxygen from
      another malonato filling the apical site. Complex 2 is made up of discrete mono-,
      di-, and trinuclear copper(II) complexes of the formulas [Cu(C3H2O4)2(H2O)2]2-,
      [[Cu(H2O)4] [Cu(C3H2O4)2(H2O)2]], and [[Cu(H2O)4]2[Cu(C3H2O4)2(H2O)]]2+,
      respectively, which coexist in a single crystal. The copper environment in the
      mononuclear unit is that of an elongated octahedron with four carboxylate oxygens
      building the equatorial plane and two water molecules assuming the axial
      positions. The neutral dinuclear unit contains two types of copper atoms, one
      that is six-coordinated, as in the mononuclear entity, and another that is
      distorted square pyramidal with four water molecules building the basal plane and
      a carboxylate oxygen in the apical position. The overall structure of this
      dinuclear entity is nearly identical to that of compound 3. Finally, the cationic
      trimer consists of an aquabis(malonato)copper(II) complex that acts as a
      bismonodentate ligand through two cis-carboxylato groups (anti-syn coordination
      mode) toward two tetraaqua-copper(II) terminal units. The environment of the
      copper atoms is distorted square pyramidal with four carboxylate oxygens (four
      water molecules) building the basal plane of the central (terminal) copper atom
      and a water molecule (a carboxylate oxygen) filling the axial position. The
      magnetic properties of 1-3 have been investigated in the temperature range 1.9
      290 K. Overall, ferromagnetic behavior is observed in the three cases: two weak,
      alternating intrachain ferromagnetic interactions (J = 3.0 cm-1 and alpha J = 1.9
      cm-1 with H = -J sigma i[S2i.S2i-1 + alpha S2i.S2i+1]) occur in 1, whereas the
      magnetic behavior of 2 is the sum of a magnetically isolated spin doublet and
      ferromagnetically coupled di- (J3 = 1.8 cm-1 from the magnetic study of the model
      complex 3) and trinuclear (J = 1.2 cm-1 with H = -J (S1.S2 + S1.S3) copper(II)
      units. The exchange pathway that accounts for the ferromagnetic coupling, through
      an anti-syn carboxylato bridge, is discussed in the light of the available
      magneto-structural data.

PMID- 12526438
TI  - Binding of phosphate with a simple hexaaza polyammonium macrocycle.
AB  - A mixture of dihydrogen phosphate and phosphoric acid has been crystallized with
      a hexaprotonated 26-membered polyammonium macrocycle, 1,4,7,14,17,20
      hexaazacyclohexacosane, as the counterion. The complex crystallizes in the
      monoclinic space group P2(1)/c with unit cell parameters of a = 10.006(2) A, b =
      12.525(1) A, c = 19.210(2) A, beta = 102.91(1) degrees, and V = 2346.6(5) A3. The
      hexaprotonated macrocycle is located on a crystallographic center of inversion
      and is surrounded by eight phosphate anions. Six of the phosphates are dihydrogen
      phosphates (H2PO4-), and the other two are neutral phosphoric acid molecules.
      Intricate hydrogen-bonding networks, involving the anionic and neutral phosphates
      and the protonated macrocycle, dominate the crystal lattice. Potentiometric
      studies using NaCl as the supporting electrolyte indicate high formation
      constants for the triprotonated macrocycle, H3L3+, with PO4(3-) at pH
      approximately 9.5 (log K = 4.55(4)), for the tetraprotonated macrocycle, H4L4+,
      with monohydrogen phosphate, HPO4(2-), at pH approximately 8.0 (log K = 6.01(3)),
      and for ditopic complexes with H5L5+ and H6L6+ and dihydrogen phosphate, H2PO4-,
      at pH approximately 4.0 (log K = 6.16(6)) and pH approximately 2.5 (log K =
      6.44(5)), respectively. The ditopic behavior in the simple polyazamacrocycle
      receptor is a somewhat unusual occurrence, as is the finding of phosphoric acid
      species in the crystal structure.

PMID- 12526439
TI  - Polynuclear chromium(III) carboxylates. 1. Synthesis, structure, and magnetic
      properties of an octanuclear complex with a ring structure.
AB  - A novel cyclic octanuclear chromium(III) complex with hydroxo and acetato
      bridging ligands was isolated and its structure determined by X-ray
      crystallography. The complex [Cr8(OH)12(OAc)12] (1) (OAc- = CH3CO2-), as found in
      crystals of 1.34H2O, is obtained by refluxing an aqueous solution of the
      trinuclear "basic" chromium acetate. 1.34H2O crystallizes in the tetragonal space
      group I42d with the following unit cell dimensions: a = 16.592(2) A, c =
      31.557(4) A, V = 8687(1) A3, and Z = 2. A total of 2000 unique data with I > 3
      sigma (I) were used to solve and refine the structure to R(Fo) = 0.066 and Rw(Fo)
      = 0.085. The structure consists of eight Cr(III) ions that form a ring structure
      and are bridged by hydroxo and acetato ligands. Each of the two neighboring metal
      atoms in 1 is bridged either by two OH- ligands and one OAc- ligand, with a
      Cr...Cr distance of 2.949(2) A, or by two OAc- ligands and one OH- ligand, with a
      Cr...Cr distance of 3.383(2) A in an alternating fashion. The complex resides on
      a crystallographic 4 center, and the overall symmetry of 1 is S4. The magnetic
      susceptibility of 1.34H2O was measured in the temperature range of 5-240 K. Our
      theoretical modeling of the susceptibility data indicates alternating
      antiferromagnetic exchange interactions between adjacent spin 3/2 Cr3+ ions
      around the ring, of magnitude J/kB = 13.7 and 8.9 K, respectively.

PMID- 12526440
TI  - Synthesis, spectral characterization, and structural studies of 2-aminobenzoate
      complexes of divalent alkaline earth metal ions: X-ray crystal structures of
      [Ca(2-aba)2(OH2)3]infinity, [[Sr(2-aba)2(OH2)2].H2O]infinity, and [Ba(2
      aba)2(OH2)]infinity (2-abaH = 2-NH2C6H4COOH).
AB  - Reactions of alkaline earth metal chlorides with 2-aminobenzoic acid (2-abaH)
      have been investigated. The treatment of MCl2.nH2O (M = Mg, Ca, Sr or Ba) with 2
      abaH in a 1:2 ratio in a MeOH/H2O/NH3 mixture leads to the formation of
      anthranilate complexes [Mg(2-aba)2] (1), [Ca(2-aba)2(OH2)3]infinity (2), [[Sr(2
      aba)2(OH2)2].H2O)]infinity (3), and [Ba(2-aba)2(OH2)]infinity (4) respectively.
      Alternatively, these products can also be obtained starting from the
      corresponding metal acetates. Anthranilate complexes 1-4 have been characterized
      with the aid of elemental analysis, pH measurements, thermal analysis, and
      infrared, ultraviolet, and NMR (1H and 13C) spectroscopic studies. All the
      products are found to be thermally very stable and do not melt on heating to 250
      degrees C. Thermal studies of complexes 2-4, however, indicate the loss of
      coordinated and lattice water molecules below 200 degrees C. In the case of the
      magnesium complex, the analytical and thermogravimetric studies indicate the
      absence of any coordinated or uncoordinated water molecules. Further, the solid
      state structures of metal anthranilates 2-4 have been established by single
      crystal X-ray diffraction studies. While the calcium ions in 2 are
      heptacoordinated, the strontium and barium ions in 3 and 4 reveal a coordination
      number of 9 apart from an additional weak metal-metal interaction along the
      polymeric chains. The carboxylate groups show different chelating and bridging
      modes of coordination behavior in the three complexes. Interestingly, apart from
      the carboxylate functionality, the amino group also binds to the metal centers in
      the case of strontium and barium complexes 3 and 4. However, the coordination
      sphere of 2 contains only O donors. All three compounds form polymeric networks
      in the solid state with the aid of different coordinating capabilities of the
      carboxylate anions and O-H...O and N-H...O hydrogen bonding interactions.

PMID- 12526441
TI  - 207Pb-1H two-dimensional NMR spectroscopy: a useful new tool for probing lead(II)
      coordination chemistry.
AB  - Despite the fact that lead poisoning is the most common disease of environmental
      origin in the United States, the spectroscopic properties of aqueous Pb(II)
      coordination compounds have not been extensively investigated. Spectroscopic
      techniques that can be used to probe the fundamental coordination chemistry of
      Pb(II) will aid in both the development of water-soluble ligands that bind lead
      both tightly and selectively and the characterization of potential biological
      targets. Here, we report the preparation and characterization of a series of
      Pb(II) complexes of amido- derivatives of EDTA. The 207Pb chemical shift observed
      in these complexes (2441, 2189, and 1764 ppm for [Pb(EDTA)]2-, Pb(EDTA-N2), and
      [Pb(EDTA-N4)]2+, respectively) provides an extremely sensitive measure of the
      local environment and the charge on each complex. These shifts help to map out
      the lead chemical shift range that can be expected for biologically relevant
      sites. In addition, we report the first two-dimensional 207Pb-1H heteronuclear
      multiple-quantum correlation (HMQC) nuclear magnetic resonance spectra and
      demonstrate that this experiment can provide useful information about the lead
      coordination environment in aqueous Pb(II) complexes. Because this technique
      allows 207Pb-1H couplings through three bonds to be identified readily, 207Pb-1H
      NMR spectroscopy should prove useful for the investigation of Pb(II) in more
      complex systems (e.g., biological and environmental samples).

PMID- 12526442
TI  - A unique distortion in K1/3Ba2/3AgTe2: X-ray diffraction determination and
      electronic band structure analysis of its incommensurately modulated structure.
AB  - The incommensurately modulated structure of a square Te-net, namely that of
      K1/3Ba2/3AgTe2, is determined from single-crystal X-ray diffraction data within a
      (3+1)D higher dimension formalism. The phase is shown to crystallize in the
      monoclinic symmetry, P2(1)(alpha 0 gamma) superspace group with the following
      lattice parameters: a = 4.6441(10) A, b = 4.6292(12) A, c = 23.765(9) A, and beta
      = 101.28(2) degrees with q = 0.3248(6)a* -0.071(8)c*, that is, in a symmetry
      different from that reported for the average structure (tetragonal) or that
      assumed from electron diffraction measurements (orthorhombic). After the
      introduction of a crenel function for the Te displacive description, the
      refinement converged to a residual factor R = 0.033 for 2583 observed reflections
      and 115 parameters (R = 0.024 and 0.101 for 1925 main reflections and 658 first
      order satellites, respectively). The [Ag2-Te2] and the Ba/K layers are found to
      be only weakly modulated. The modulation of the square Te-net is, however, both
      substantial and unique. Namely, it results in two different units: a "V"-shaped
      Te3 trimer and a "W"-shaped Te5 pentamer. To examine both unit types, which are
      segregated in domains that aperiodically alternate within the Te layers, first
      principles electronic band structure calculations were carried out for three
      model commensurate structures using the tight-binding linear-muffin-tin-orbital
      method (LMTO). The calculations show that the distorted structures of V-pattern
      (model 2) and W-pattern (model 3) are more stable than the average structure
      (model 1) and that the V-pattern distortion provides a slightly larger
      stabilization than does the W-pattern distortion. The Fermi surface calculated
      for the average structure shows nesting vectors that are consistent with the
      occurrence of the V- and W-pattern distortions in the Te layers. However, these
      vectors do not predict the observed modulation vector of the incommensurately
      distorted structure, because the stabilization energy associated with the
      distortion is not mainly dominated by the energy lowering of the occupied band
      levels near the Fermi level.

PMID- 12526443
TI  - alpha- and beta-cyclodextrin rotaxanes of mu-bis(4
      pyridyl)bis[pentacyanoferrate(II)] complexes.
AB  - The kinetics and mechanism of the self-assemblies of alpha- and beta-cyclodextrin
      (CD) [2]rotaxanes, [(NC)5Fe-[pyRpy.CD]Fe(CN)5]6-, containing
      pentacyanoferrate(II)-stoppered 4,4'-bis(pyridyl) threads pyRpy (R = -CH = CH-, 
      N=N-, -CH=N-N=CH-, and -C(CH3)=N-N=C(CH3)-) have been investigated in aqueous
      solution by using visible and 1H NMR spectroscopy. The rotaxanes may be formed
      rapidly by the addition of the [Fe(CN)5OH2]3- ion to the CD-included pyRpy thread
      or slowly by the addition of an excess of CD to the dimeric
      [(NC)5Fe(pyRpy)Fe(CN)5]6- complex. In the latter method, the mechanism involves a
      rate-determining dissociation of a [Fe(CN)5]3- center to form the monomeric
      complex, which subsequently includes the coordinated pyRpy in the CD cavity to
      yield the semirotaxane, which is rapidly recomplexed by the [Fe(CN)5OH2]3- ion,
      generating the [2]rotaxane. Rate and activation parameters and CD inclusion
      stability constants have been determined for the ligand substitution reactions
      involving the formations and dissociations of the semirotaxanes and rotaxanes.
      The extents of the decreases in the formation (kf) and dissociation (kd) rate
      constants upon CD inclusions of the free and coordinated ligands, respectively,
      are related to the natures of the CD hosts and the R linkage on the pyRpy guests.
      The semirotaxanes and rotaxanes exhibit significant bathochromic shifts in their
      visible MLCT transitions compared with the corresponding monomeric and dimeric
      iron complexes. A correlation between the extent of the decrease in kd and the
      change in the MLCT energy upon alpha-CD inclusions of [Fe(CN)5L]3-, where L is an
      aromatic N-heterocyclic 4-Rpy or pyRpy ligand, has been observed.

PMID- 12526444
TI  - Density functional description of the early stages of the dioxygenation of
      [(MeC(CH2PPh2)3)M(catecholate)]+ complexes [M = Co(III), Ir(III)]: toward a
      rationalization of the catalytic mechanism of ring-opening dioxygenases.
AB  - Density Functional Theory (DFT) has been applied to characterize the early stages
      of the reaction of dioxygenation of [(triphos)M(catecholate)]+ complexes [M =
      Co(III), Ir(III); triphos = MeC(CH2PPh2)3], which have been considered to be
      models of ring-opening dioxygenases. The structural features of the starting
      complexes and of the intermediate complexes formed by addition of O2 to the
      coordinated catecholato ion are well reproduced. The calculations showed that
      this preliminary stage can be obtained only when the oxygen molecule attacks the
      molecule on the catecholato site.

PMID- 12526445
TI  - Three-dimensional open-framework cobalt(II) phosphates by novel routes.
AB  - Two new three-dimensional open-framework cobalt phosphates,
      [C2N2H10]2[Co4(PO4)4]H2O, I, and [C4N3H16]3-[Co6(PO4)5(HPO4)3]H2O, II, have been
      prepared by the reaction of amine phosphates with Co2+ salts. I could also be
      prepared by the reaction of the cobalt tris amine complex with H3PO4. The crystal
      data for I and II are as follows: phosphate I, orthorhombic, space group
      P2(1)2(1)2(1) (no. 19), a = 10.277 (1) A, b = 10.302 (1) A, c = 18.836 (1) A, V =
      1994.2 (2) A3, Z = 4; phosphate II, monoclinic, space group P2(1)/c (No. 14), a =
      31.950 (1) A, b = 8.360 (1) A, c = 15.920 (1) A, beta = 96.6 (1) degrees V =
      4223.4 (2) A3, Z = 4. The structures of both I and II are constructed from
      alternating CoO4 and PO4 tetrahedra. The connectivity leads to the formation of
      eight-membered channels in all the crystallographic directions resembling the
      aluminosilicate zeolite, merlinoite in the case of I and to a rather large, one
      dimensional 16-membered channel in II. Strong hydrogen-bond interactions
      involving the amine and framework oxygen are present in both I and II.

PMID- 12526446
TI  - Stepwise assembly of unsymmetrical supramolecular arrays containing porphyrins
      and coordination compounds.
AB  - The stepwise coordination of meso-4'-pyridyl/phenyl porphyrins (4'-PyPs) to
      different metal centers proved to be an efficient synthetic approach leading to
      unsymmetrical arrays containing porphyrins and coordination compounds. The first
      step of this process, treatment of 4'-PyPs with a less than stoichiometric amount
      of cis,fac-RuCl2(Me2-SO)3(CO) (1), leads to the selective coordination of
      [cis,cis,cis-RuCl2(Me2SO)2(CO)] fragments ([Ru]) to some of the peripheral 4'-N
      sites of the 4'-PyPs. Column separation afforded four partially ruthenated 4'
      PyPs in pure form: 4'-cis-DPyP[Ru] (2), 4'-trans-DPyP[Ru] (3), (4'-TPyP)[Ru] (4),
      and (4'-TPyP)[Ru]3 (5). These compounds, which have residual unbound peripheral
      4'-N(py) sites (either one or three), were allowed to react with other metal
      centers that may belong either to a metalloporphyrin or to a coordination
      compound. When building blocks 2-5 were treated with [Ru(TPP)(CO)(EtOH)] (TPP =
      meso-tetraphenylporphyrin) in chloroform at room temperature, axial coordination
      of Ru(TPP)(CO) units ((Ru)) to the available 4'-N(py) sites readily occurred,
      generating the following arrays containing both perpendicular porphyrins and
      coordination compounds: (Ru)-(mu-4'-cis-DPyP)[Ru], (Ru)(mu-4'-trans-DPyP)[Ru],
      (Ru)3(mu-4'-TPyP)[Ru], and (Ru)(mu-4'-TPyP)[Ru]3. Furthermore, building blocks 2,
      3, and 5 were treated with a series of coordination compounds capable of binding
      two pyridylporphyrins either cis to each other (trans-RuCl2(Me2SO)4 and
      trans,cis,cis-RuCl2(Me2SO)2(CO)2) or trans to each other (trans-PdCl2(C6H5CN)2).
      Homo- (Ru) and heterobimetallic (Ru-Pd) arrays with as many as seven metal atoms
      (six Ru and one Pd) and two 4'-PyPs were obtained as follows: trans,cis,cis
      RuCl2(Me2SO)2(4'-cis-DPyP[Ru])2, trans,cis,cis-RuCl2(Me2SO)2(4'-trans-DPyP[Ru])2,
      trans,cis,cis-RuCl2(CO)2(4'-cis-DPyP[Ru])2, and trans-PdCl2(4'-TPyP[Ru]3)2. All
      the products were thoroughly characterized by 1H NMR spectroscopy. Since the [Ru]
      fragment is chiral, diastereomers are formed when two or more [Ru] units are
      bound to a porphyrin. We found that when two 4'-cis-DPyP[Ru] (2) units are
      coordinated cis to each other on the same metal center, the mutual anisotropic
      effect of the cis porphyrins differentiates the sulfoxide methyl resonances for
      the two forms. These and other results indicate that the pyridyl units react
      independently of the presence or absence of a substituent on the other py rings.
      Thus, the synthetic strategy should be a general method for linking diverse metal
      centers through pyridylporphyrins.

PMID- 12526447
TI  - Formation and dissociation kinetics and crystal structures of nickel(II)
      macrocyclic tetrathiaether complexes in acetonitrile. Comparison to nickel(II)
      macrocyclic tetramines.
AB  - Complex formation and dissociation rate constants have been independently
      determined for solvated nickel(II) ion reacting with eight macrocyclic
      tetrathiaether ligands and one acyclic analogue in acetonitrile at 25 degrees C,
      mu = 0.15 M. The macrocyclic ligands include 1,4,8,11-tetrathiacyclotetradecane
      ([14]aneS4) and seven derivatives in which one or both ethylene bridges have been
      substituted by cis- or trans-1,2-cyclohexane, while the acyclic ligand is
      2,5,9,12-tetrathiatridecane (Me2-2,3,2-S4). In contrast to similar complex
      formation kinetic studies on Ni(II) reacting with corresponding macrocyclic
      tetramines in acetonitrile and N,N-dimethylformamide (DMF), the kinetics of
      complex formation with the macrocyclic tetrathiaethers show no evidence of slow
      conformational changes following the initial coordination process. The differing
      behavior is ascribed to the fact that such conformational changes require donor
      atom inversion, which is readily accommodated by thiaether sulfurs but requires
      abstraction of a hydrogen from a nitrogen (to form a temporary amide). The latter
      process is not facilitated in solvents of low protophilicity. The rate
      determining step in the formation reactions appears to be at the point of first
      bond formation for the acyclic tetrathiaether but shifts to the point of chelate
      ring closure (i.e., second-bond formation) for the macrocyclic tetrathiaether
      complexes. The formation rate constants for Ni(II) with the macrocyclic
      tetrathiaethers parallel those previously obtained for Cu(II) reacting with the
      same ligands in 80% methanol-20% water (w/w). By contrast, the Ni(II)
      dissociation rate constants show significant variations from the trends in the
      Cu(II) behavior. Crystal structures are reported for the Ni(II) complexes formed
      with all five dicyclohexanediyl-substituted macrocyclic tetrathiaethers. All but
      one are low-spin species.

PMID- 12526448
TI  - Molybdenum(V) on an oxide string. Formation and solution stability of the linear
      complex (mu-trans-dioxo(tetraphenylporphyrinato)molybdenato(V))-
      bis(oxo(tetraphenylporphyrinato)molybdenum(V)) perchlorate.
AB  - The unusual linear trinuclear complex [Mo3O4(TPP)3]+ is formed in solution upon
      the reaction of [MoO(TPP)-(OClO3)] with [[MoO(TPP)]2O], and an equilibrium
      between [Mo3O4(TPP)3]+ and its constituent species is rapidly established.
      Spectrophotometric experiments suggest that [Mo3O4(TPP)3]+ is the predominant
      species found in solutions resulting from the mixture of [MoO(TPP)(OClO3)] and
      [[MoO(TPP)]2O], and its formation is strongly favored (log K = 5.5 +/- 0.5 M-1).
      No evidence of higher oligomers has been observed. A mechanism for the formation
      of [Mo3O4(TPP)3]+ by the controlled hydrolysis of [MoO(TPP)(OClO3)] is proposed.

PMID- 12526449
TI  - Catalysis and kinetics of hydrogen peroxide disproportionation by dinuclear
      manganese(III) complexes of 1,5-bis(salicylidenamino)pentan-3-ol and the 5
      bromophenyl-substituted derivative.
AB  - The dinuclear MnIII complex [Mn2(mu-OAc)(mu-OMe)(5-Br-salpentO)(MeOH)2]Br has
      been prepared and its structure and reactivity toward H2O2 studied in comparison
      with [Mn2(mu-OAc)(mu-OMe)(salpentO)(MeOH)2]Br (salpent-OH = 1,5
      bis(salicylidenamino)pentan-3-ol and 5-Br-salpentOH = 1,5-bis(5
      bromesalicylidenaminopentan-3-ol). The X-ray diffraction analysis of [Mn2(mu
      OAc)(mu-OMe)(5-Br-salpentO)(MeOH)2]Br (monoclinic, P21/n, a = 13.081(2) A, b =
      13.429(2) A, c = 17.375(2) A, beta = 102.31(1) degrees, V = 2982.0 A3, Z = 4)
      revealed a mu-alkoxo, mu-acetatodimanganese(III) core with a Mn...Mn separation
      of 2.932(1) A. The ligand lies in the meridional plane, and the sixth
      coordination position of each manganese atom is occupied by a methanol molecule
      providing two substitution-labile sites in the cis position. The two complexes
      showed catalytic activity toward disproportionation of H2O2 in methanol and
      dimethylformamide in the 0-25 degrees C temperature range. The initial rate of
      oxygen evolution in the presence of [Mn2(mu-OAc)(mu-OMe)(5-Br-salpentO)(MeOH)2]Br
      or [Mn2(mu-OAc)(mu-OMe)(salpentO)(MeOH)2]-Br is first order in catalyst
      concentration. The two complexes show saturation kinetics in methanol, with the
      higher kcat = 0.98 s-1 and kcat/KM = 70 M-1 s-1 observed for [Mn2(mu-OAc)(mu
      OMe)(salpentO)(MeOH)2]Br.

PMID- 12526450
TI  - Conformation of heterocycles controlled by the existence of unusual C-H...X
      hydrogen bonds: syntheses and structure determination of aluminum aryloxides.
AB  - The reactions of AlMe3 in diethyl ether with 1 molar equiv of 2,2'-methylenebis(4
      methyl-6-tert-butylphenol) (MMBP-H2), 2,2'-methylenebis(4,6-di-tert-butylphenol)
      (MDBP-H2), and 2,2'-ethylidenebis(4,6-di-tert-butylphenol) (EDBP-H2) afford
      series of four-coordinate monomeric aluminum aryloxides, MeAl(O-O)(OEt2), 1-3 (1,
      (O-O) = MMBP; 2, (O-O) = MDBP; 3, (O-O) = EDBP). In THF, 1 molar equiv of EDBP-H2
      reacts with AlMe3 to provide the THF-coordinated complex MeAl(EDBP)(THF) 4.
      However, in the absence of a coordinating solvent, the reaction of EDBP-H2 with
      AlMe3 yields the dimeric complex [MeAl(mu-EDBP)]2 (5). Complex 5 further reacts
      with Et4NCl, Et4NBr, and Ph3PO to afford the corresponding monomeric ionic
      complex [Et4N][MeAl(EDBP)(X)] (6, X = Cl; 7, X = Br) and the neutral complex
      [MeAl(EDBP)(O=PPh3)] (8), respectively. Complexes 1, 2, 4 and 6-8 are subjected
      to X-ray structure analyses, and the solid state structures reveal that the
      conformations of the eight-membered heterocycles are governed by the formation of
      the unusual C-H...X hydrogen bonds.

PMID- 12526451
TI  - Hydrothermal synthesis and magnetic behavior of a novel layered coordination
      polymer generated from manganese(II) adipate.
AB  - A novel, two-dimensional organic/inorganic coordinate polymers,
      Mn2(H2O)[O2C(CH2)4CO2]2, was synthesized as single crystals by the hydrothermal
      reaction of MnCl2 with adipic acid in the presence of base and characterized by
      single-crystal X-ray diffraction, infrared spectroscopy, thermal analysis, and
      SQUID magnetic measurement. It crystallized in the monoclinic space group
      C2/c(No. 15), with a = 21.671(2) A, b = 7.6023(7) A, c = 9.1452(9) A, beta =
      108.849(7) A, Z = 4. The title compound presents a structure constituted by the
      stacking along [100] of MnO6 layers interleaved with adipate ions. The novel
      feature of the anionic layer is that it contains close-packed trans alkyl chains
      residing in an extended framework. Magnetization measurement shows this compound
      is antiferromagnetic below 15 K.

PMID- 12526452
TI  - The first organo-templated cobalt phosphate with a zeolite topology.
AB  - An organic molecule containing cobalt phosphate (denoted CoPO-GIS) which is
      isostructural with the zeolite gismondine has been synthesized under solvothermal
      conditions by using [Co(en)3]Cl3 and phosphoric acid as the reactants and
      ethylene glycol as the solvent. CoPO-GIS ((H3NCH2CH2NH3)0.5.CoPO4) crystallizes
      in the monoclinic space group C2/c with a = 14.744(3) A, b = 8.850(3) A, c =
      10.062(3) A, beta = 131.609(19) degrees, and Z = 8. The structure consists of a 3
      D network of strictly alternating CoO4 and PO4 tetrahedra interconnected by
      oxygen bridges, and the charge-balancing diprotonated ethylenediamine cations are
      highly ordered in the cages of the CoPO4 framework. CoPO-GIS is the only amine
      containing cobalt phosphate with a known zeolite topology.

PMID- 12526453
TI  - Synthesis and characterization of racemic mixture and meso isomers of bis(trans-2
      aminocyclohexyl)aminepentaacetic acid and the stabilities of their Gd(III)
      complexes.
AB  - The synthesis and characterization of two multidentate ligands, the racemic
      mixture and meso isomers of bis-(trans-2-aminocyclohexyl)aminepentaacetic acid,
      are described. Equilibrium constants for their Gd(III) complexes were determined
      by direct potentiometry. The formation constants (KML = [ML]/[M][L]) of Gd(III)
      Cycyracemic in 0.10 M KCl at 25.0 degrees C is 10(20.71; that for the meso isomer
      is 10(20.42). The crystal structure of (1S,2S,1'S,2'S)-bis(trans-2
      aminocyclohexyl)amine-N,N,N',N",N"-pentaacetic acid, penta-tert-butyl ester
      (C42H75N3O10), is reported. This compound crystallizes in the triclinic system
      with space group P1 with cell parameters a = 10.805(2) A, b = 11.382(2) A, c =
      20.999(4) A, alpha = 91.41(3) degrees, beta = 98.23(3) degrees, gamma = 113.88(3)
      degrees, V = 2327.8(8) A3, Z = 2, Dx = 1.116 g mL-1. The results are compared to
      the crystal structures of the gadolinium complexes and the predictions derived
      from molecular mechanics.

PMID- 12526454
TI  - Crystallographic, X-ray absorption, and IR studies of solid- and solution-state
      structures of tris(nitrato) N,N,N',N'-tetraethylmalonamide complexes of
      lanthanides. Comparison with the Americium complex.
AB  - To fine-tune the design of optimized donor ligands for nuclear waste actinide
      selective extraction, both electronic and molecular structures of the actinide
      complexes that are formed must be investigated. In particular, to achieve the
      selective complexation of transplutonium 3+ ions versus lanthanide 3+ ions is one
      of the major challenges, given the chemical similarities between these two f
      element families. In this work, the structure of solvent-phase M(NO3)3(TEMA)2
      complexes (Ln = Nd, Eu, Ho, Yb, Lu, Am; TEMA = N,N,N',N'-tetraethylmalonamide)
      was investigated by liquid-phase spectroscopic methods among which extended X-ray
      absorption fine structure played a major role. In addition, the crystal
      structures of the species Nd(NO3)3(TEMA)2 and Yb(NO3)3(TEMA)2 have been
      determined by X-ray diffraction. Nd(NO3)3(C11N2O2H22)2 crystallizes in the
      monoclinic system (P2(1) space group; a = 11.2627(4) A, b = 20.5992(8) A, c =
      22.2126(8) A; alpha = gamma = 90 degrees, beta = 102.572(1) degrees; Z = 6), and
      Yb(NO3)3(C11N2O2H22)2 crystallizes in the orthorhombic system (P2(1)2(1)2(1)
      space group; a = 9.3542(1) A, b = 18.1148(2) A, c = 19.7675(2) A; alpha = beta =
      gamma = 90 degrees; Z = 4). In the solvent phase, the metal polyhedron was found
      to be similar to that of the solid-state complex Nd(NO3)3(TEMA)2 for M = Nd to
      Ho. For M = Yb and Lu, a significant elongation of one nitrate oxygen bond was
      observed. Comparison with measurements on the Am(NO3)3(TEMA)2 complex in ethanol
      has shown the similarities between the Nd3+ and Am3+ coordination spheres.

PMID- 12526455
TI  - Trigonal prismatic vs octahedral coordination geometry: syntheses and structural
      characterization of hexakis(arylthiolato) zirconate complexes.
AB  - Treating [Li(tmeda)]2[Zr(CH3)6] with aryl thiols, HSC6H4-4-R, in a 1:6
      stoichiometry in diethyl ether affords excellent yields of [Li(tmeda)]2[Zr(SC6H4
      4-R)6], where R = CH3 (1(2-)) or OCH3 (2(2-)) and tmeda denotes N,N,N',N'
      tetramethylethylenediamine. These complexes are air-sensitive canary-yellow
      solids, soluble in hexane, diethyl ether, THF, and acetonitrile, that form yellow
      single crystals of [Li(tmeda)](2)1 (diethyl ether solution) or [Li(THF)3](2)2
      (THF solution) from saturated solutions at -20 degrees C. Both complexes were
      characterized by X-ray crystallography and consist of a zirconium atom
      coordinated solely by the sulfur atoms of six aryl thiolate ligands in a
      nonoctahedral geometry. In each structure the lithium cation coordinates to the
      three sulfur atoms on the triangular faces of the S6 pseudotrigonal prism. These
      lithium-sulfur interactions appear to play a role in determining the coordination
      geometry about the metal center by orienting the sulfur lone pairs of electrons
      slightly out of the plane defined by the S3 triangular face and tilted away from
      the zirconium atoms. A likely consequence is the positioning of the sulfur lone
      pairs of electrons away from orthogonality with the zirconium-sulfur vector, and
      hence, they are poorly arranged to pi-interact with zirconium. Complex 1(2-) with
      a twist angle of ca. 9.18 degrees (trigonal prism, 0 degree; octahedron, 60
      degrees) agrees with the interpretations of computational studies on d degree
      complexes, which suggest that a nearly trigonal prismatic geometry is favored
      when the interaction between metal and ligand is primarily through sigma-bonds.
      The intrinsically weak pi-donor thiolate ligand is probably converted to a
      primarily sigma-bonding system by the lithium-sulfur interaction. On the other
      hand complex 2(2-) with a twist angle of ca. 30.38 degrees is trigonally twisted
      to the midpoint of the trigonal prismatic-to-octahedral reaction coordinate. In
      complex 2(2-) the 4-OCH3 group is an electron donor by resonance effects that
      possibly may lead to the movement away from the expected trigonal prismatic
      geometry due to either pi-interactions or electrostatics repulsion.

PMID- 12526457
TI  - Evidence of bilayer structure in V2O5 xerogel.
AB  - Polarized X-ray absorption spectroscopy has been used to study the short-range
      structure of deposited films of V2O5 xerogel. The material is characterized by a
      layer of VO5 units with the V-O apical bond perpendicular to the basal (xy)
      plane. We have focused our attention along the z axis. Experiments were carried
      out by extended X-ray absorption fine structure (EXAFS) spectroscopy in a grazing
      incidence geometry and showed evidence for close interactions between neighboring
      layers of V2O5. The structure is described by two sheets of V2O5 facing each
      other. Fitting of the EXAFS data has confirmed the existence of a vanadium
      vanadium interaction between two different V2O5 layers and an oxygen bridge
      between them.

PMID- 12526456
TI  - Tetranuclear manganese carboxylate complexes with a trigonal pyramidal metal
      topology via controlled potential electrolysis.
AB  - Controlled potential electrolysis (CPE) procedures are described that provide
      access to complexes with a [Mn4(mu 3-O)3(mu 3-O2CR)]6+ core (3MnIII,MnIV) and a
      trigonal pyramidal metal topology, starting from species containing the [Mn4(mu 3
      O)2]8+ core (4MnIII). [Mn4O2(O2CMe)6(py)2(dbm)2] (6): triclinic, P1, a =
      10.868(3) A, b = 13.864(3) A, c = 10.625(3) A, alpha = 108.62(1) degrees, beta =
      118.98(1) degrees, gamma = 89.34(2) degrees, V = 1307 A3, Z = 1, T = -131 degrees
      C, R (Rw) = 3.24 (3.70)%. [Mn4O2(O2CPh)6(py)(dbm)2] (8): monoclinic, P2(1)/c, a =
      14.743(6) A, b = 15.536(8) A, c = 30.006(13) A, beta = 102.79(1) degrees, V =
      6702 A3, Z = 4, T = -155 degrees C, R (Rw) = 4.32 (4.44)%. Both 6 and 8 contain a
      [Mn4O2]8+ core; 8 only has one py group, the fourth MnIII site being five
      coordinate. (NBun4)[Mn4O2(O2CPh)7(dbm)2] (10) is available from two related
      procedures. CPE of 10 at 0.65 V vs ferocene in MeCN leads to precipitation of
      [Mn4O3(O2CPh)4(dbm)3] (11); similarly, CPE of 6 at 0.84 V in MeCN/CH2Cl2 (3:1
      v/v) gives [Mn4O3(O2CMe)4(dbm)3] (12). Complex 11: monoclinic, P2(1)/n, a =
      15.161(3) A, b = 21.577(4) A, c = 22.683(5) A, beta = 108.04(3) degrees, V = 7056
      A3, Z = 4, T = -100 degrees C, R (wR2) = 8.63 (21.80)%. Complex 12: monoclinic,
      P2(1)/n, a = 13.549(2) A, b = 22.338(4) A, c = 16.618(2) A, beta = 103.74(1)
      degrees, V = 4885 A3, Z = 4, T = -171 degrees C, R (Rw) = 4.63 (4.45)%. Both 11
      and 12 contain a [Mn4(mu 3-O)3(mu-O2CR)] core with a Mn4 trigonal pyramid (MnIV
      at the apex) and the RCO2- bridging the MnIII3 base. However, in 11, the
      carboxylate is eta 2,mu 3 with one O atom terminal to one MnIII and the other O
      atom bridging the other two MnIII ions, whereas in 12 the carboxylate is eta 1,mu
      3, a single O atom bridging three MnIII ions. Variable-temperature, solid-state
      magnetic susceptibility studies on 11 and 12 show that, for both complexes, there
      are antiferromagnetic exchange interactions between MnIII/MnIV pairs, and
      ferromagnetic interactions between MnIII/MnIII pairs. In both cases, the
      resultant ground states of the complex is S = 9/2, confirmed by magnetization vs
      field studies in the 2.00-30.0 K and 0.50-50 kG temperature and field ranges,
      respectively.

PMID- 12526458
TI  - Cis-influence of hydroporphyrin macrocycles on axial ligation equilibria and
      alkyl exchange reactions of alkylcobalt(III) porphyrin complexes.
AB  - Stability constants are reported for the coordination of pyridine and substituted
      pyridines to the alkylcobalt(III) complexes of octaethylporphyrin (OEP), t
      octaethylchlorin (OEC), and ttt-octaethylisobacteriochlorin (OEiBC) in toluene
      solution. The stability constants correlate with the base strength of the
      nitrogenous ligand. A cis-influence of the macrocycle saturation level on the
      stability constants is observed. Stability constants for coordination of a given
      pyridine ligand to an alkylcobalt(III) complex are roughly 10 times smaller than
      the stability constants for the corresponding cobalt(II) complex. Analysis of a
      thermodynamic cycle demonstrates that this leads to decreased stability of the
      complex with respect to Co-C bond homolysis upon ligand coordination, a "base-on"
      effect. Alkyl exchange occurs between cobalt complexes of different
      tetrapyrroles. Equilibrium data establish that the exchange is nonstatistical and
      that the Co-C bond is stabilized by increasing the saturation of the tetrapyrrole
      macrocycle.

PMID- 12526459
TI  - LiEuPSe4 and KEuPSe4: novel selenophosphates with the tetrahedral [PSe4]3-
      building block.
AB  - LiEuPSe4, the first quaternary lithium-containing selenophosphate, was
      synthesized as red polyhedra by reacting Eu with a molten mixture of
      Li2Se/P2Se5/Se at 750 degrees C. Similarly, the reaction of Eu with a molten
      mixture of K2Se/P2Se5/Se at 495 degrees C produced red polyhedral crystals of
      KEuPSe4. Both compounds are unstable in moist air. In addition, both compounds
      were plagued with crystal twinning. Acceptable crystal structure refinements
      could only be obtained by identifying the type of twinning and taking it into
      account in the final refinement. LiEuPSe4 crystallizes in the noncentrosymmetric
      space group Ama2 (no. 40) with a = 10.5592 (9) A, b = 10.415 (1) A, c = 6.4924(7)
      A, and Z = 4. The structure is three-dimensional and composed of EuSe8 distorted
      square antiprisms and PSe4 tetrahedral building blocks that create tunnels,
      running down the a axis, in which the Li ions reside. The Li ions are in a highly
      distorted tetrahedral coordination. KEuPSe4 crystallizes in the space group
      P2(1)/m (no. 11) with a = 6.8469(6) A, b = 6.9521(6) A, c = 9.0436(8) A, beta =
      107.677(2) degrees, and Z = 2. The structure has two-dimensional character with
      layers composed of EuSe6 trigonal prisms and PSe4 tetrahedral units. Between the
      [EuPSe4]nn- layers the K ions reside in a bicapped trigonal prism of Se atoms.
      The structure of the [EuPSe4]nn- framework is similar to that found in CsPbPSe4.
      Both compounds are semiconductors with band gaps of 2.00 and 1.88 eV,
      respectively. Differential thermal analysis and infrared spectroscopic
      characterization are also reported.

PMID- 12526460
TI  - Molecular lattice fragment of LiI. Crystal structure and ab initio calculations
      of [LiI(NEt3)]4.
AB  - Numerous crystal structures of donor-stabilized LiX species are known, but only
      two of them show a heterocubane arrangement [LiX(Do)]4 (X = Cl, Br; Do = donor)
      in the solid state. Herein we report the X-ray crystal structure of [LiI(NEt3)]4
      (1), obtained by the reaction of LiN(SiMe3)2 with either GaI or All in the
      presence of NEt3. The structural backbone of 1 is a [LiI]4 heterocubane core,
      which is compared to [LiX]4 (X = Cl, Br) as well as to [Li(CH3)]4. The energetics
      of the formation of 1 and its stability with respect to solid LiI is rationalized
      and additionally supported by DFT (density functional theory) calculations.

PMID- 12526461
TI  - Electronic structures and properties of eight-coordinate metal-polyarsenic
      complexes MAs8n- (M = V, Nb, Ta, Cr, Mo, W, Mn, Tc, Re).
AB  - The eight-coordinate early transition metal polyarsenic complexes, MAs(8)3- (M =
      V, Nb, Ta), MAs(8)2- (M = Cr, Mo, W), and MAs8- (M = Mn, Tc, Re), have been
      studied using density functional theory (DFT). The geometry optimizations of
      these complexes indicate that in the most stable structures the transition metal
      atoms are trapped in a crownlike cavity consisting of a zigzag eight-membered
      ring of As8 cluster. The scalar-relativistic effects and spin-orbit coupling
      effects on the electronic structures and energy levels were taken into account.
      The stabilities of gas-phase MAs8n- ions and bonding between the As8 ring and
      early transition metals are discussed on the basis of population analysis,
      atomization energies, and decomposition reaction energies. All these complex ions
      are found to be diamagnetic with notable HOMO-LUMO energy gaps. The vibrational
      frequencies and infrared absorption intensities of the MAs8n- series are
      predicted theoretically. Brief theoretical calculations of the similar MoA(8)2-
      pnictide ions indicate that the analogous P, Sb, and even Bi complexes are likely
      to be stable, whereas the crownlike MoN(8)2- is not a stable complex.

PMID- 12526462
TI  - Structural features of Ag[AuF4] and Ag[AuF6] and the stuctural relationship of
      Ag[AgF4]2 and Au[AuF4]2 to Ag[AuF4]2.
AB  - Synchrotron radiation X-ray powder diffraction data (SPDD) have been obtained for
      Ag[AgF4]2, Au[AuF4]2, Ag[AuF4], and Ag[AuF6]. Ag[AgF4]2 and Au[AuF4]2 are
      isostructural with Ag[AuF4]2, space group (SG) P2(1)/n, Z = 2, with the
      following: for Ag[AgF4]2 a = 5.04664(8), b = 11.0542(2), c = 5.44914(9) A, beta =
      97.170(2) degrees; for Au[AuF4]2 a = 5.203(2), b = 11.186(3), c = 5.531(2) A,
      beta = 90.55(2) degrees. The structure of Ag[AgF4]2 was refined successfully
      (SPDD) applying the Rietveld method, yielding the following interatomic distances
      (A): AgII-F = 2.056(12), 2.200(13), 2.558(13); AgIII-F = two at 1.846(12), others
      = 1.887(12), 1.909(13), 2.786-(12), 2.796(12), 2.855(12). AgAuF4, like other
      AA'F4 salts (A = Na-Rb; A' = Ag, Au), crystallizes in the KBrF4 structure type,
      SG I4/mcm (140), Z = 4 with a = 5.79109(6), c = 10.81676(7) A. SPDD gave (in A)
      four AuIII-F = 1.89(1) and eight AgI-F = 2.577(7). SPDD for AgAuF6 confirmed that
      it has the LiSbF6 structure, SG R3, Z = 3, with a = 5.2840(2), c = 15.0451(6) A.

PMID- 12526463
TI  - Kinetics of manganese(III) acetate in acetic acid: generation of Mn(III) with
      Co(III), Ce(IV), and dibromide radicals; reactions of Mn(III) with Mn(II),
      Co(II), hydrogen bromide, and alkali bromides.
AB  - The reaction of cobalt(III) acetate with excess manganese(II) acetate in acetic
      acid occurs in two stages, since the two forms Co(IIIc) and Co(IIIs) are not
      rapidly equilibrated and thus react independently. The rate constants at 24.5
      degrees C are kc = 37.1 +/- 0.6 L mol-1 s-1 and ks = 6.8 +/- 0.2 L mol-1 s-1 at
      24.5 degrees C in glacial acetic acid. The Mn(III) produced forms a dinuclear
      complex with the excess of Mn(II). This was studied independently and is
      characterized by the rate constant (3.43 +/- 0.01) x 10(2) L mol-1 s-1 at 24.5
      degrees C. A similar interaction between Mn(III) and Co(II) is substantially
      slower, with k = (3.73 +/- 0.05) x 10(-1) L mol-1 s-1 at 24.5 degrees C. Mn(II)
      is also oxidized by Ce(IV), according to the rate law -d[Ce(IV)]/dt =
      k[Mn(II)]2[Ce(IV)], where k = (6.0 +/- 0.2) x 10(4) L2 mol-2 s-1. The reaction
      between Mn(II) and HBr2., believed to be involved in the mechanism by which
      Mn(III) oxidizes HBr, was studied by laser photolysis; the rate constant is (1.48
      +/- 0.04) x 10(8) L mol-1 s-1 at approximately 23 degrees C in HOAc. Oxidation of
      Co(II) by HBr2. has the rate constant (3.0 +/- 0.1) x 10(7) L mol-1 s-1. The
      oxidation of HBr by Mn(III) is second order with respect to [HBr]; k = (4.10 +/-
      0.08) x 10(5) L2 mol-2 s-1 at 4.5 degrees C in 10% aqueous HOAc. Similar
      reactions with alkali metal bromides were studied; their rate constants are 17-23
      times smaller. This noncomplementary reaction is believed to follow that rate law
      so that HBr2. and not Br. (higher in Gibbs energy by 0.3 V) can serve as the
      intermediate. The analysis of the reaction steps then requires that the oxidation
      of HBr2. to Br2 by Mn(III) be diffusion controlled, which is consistent with the
      driving force and seemingly minor reorganization.

PMID- 12526464
TI  - Controlled molecular motions in copper-complexed rotaxanes: an XAS study.
AB  - The environment of the central metal of a molecular machine-like copper rotaxane
      was observed by XAS experiments. The wheel of the rotaxane is a hetero
      bischelating macrocycle containing both bidentate (phenanthroline) and terdentate
      (terpyridine) moieties. The axle of the assembly contains only a bidentate
      moiety. Applying an external chemical stimulus-oxidation of the metal-increases
      the number of coordinating atoms required by the metal template from 4 to 5. This
      variation is consistent with the oscillation of the wheel around the axle,
      leading thus to the most stable environment for the metal in the Cu(II) rotaxane.

PMID- 12526465
TI  - Syntheses and structures of methyltris(pyrazolyl)silane complexes of the group 6
      metals.
AB  - The methyltris(3,5-dimethylpyrazolyl)silane ligand, TpsMe2, was readily prepared
      by the metathesis reaction of methyltrichlorosilane with 3 equiv of lithium 3,5
      dimethylpyrazolate. The octahedral tricarbonyl complexes (TpsMe2)M(CO)3 were
      synthesized either by ligand exchange with the labile nitrile adducts
      M(CO)3(NCR)3 (M = Cr, Mo, R = Me; M = W, R = Et) or thermally by direct
      substitution on the hexacarbonyls M(CO)6 (M = Cr, Mo). The three new complexes
      were characterized by a combination of analytical and spectroscopic techniques,
      including electrospray ionization mass spectrometry and single-crystal X-ray
      diffraction. They are all isostructural and display in the solid state the
      expected distorted octahedral geometries with facially coordinated
      tris(pyrazolyl)silane ligands. Crystallographic data were used to calculate the
      ligand cone angles (251-264 degrees) in (TpsMe2)M(CO)3 and also to estimate a
      value of 1.59 A for the covalent radius of octahedral W(0).

PMID- 12526466
TI  - Unusual ligand coordination for cesium.
AB  - When complexed by tetrabenzo-24-crown-8, the cesium ion can accommodate
      unprecedented ligation. The structures of the following complexes are presented.
      [Cs(tetrabenzo-24-crown-8)(eta 1-NCMe)2(eta 2-NCMe)][NO3] (1): triclinic P1, a =
      12.0119(14) A, b = 13.3680(15) A, c = 13.7859(12) A, alpha = 89.124(8) degrees,
      beta = 66.928(9) degrees, gamma = 71.536(10) degrees, V = 1916.7(4) A3, Z = 2.
      [Cs(tetrabenzo-24-crown-8)(eta 1-NCMe)2(eta 2-CH2Cl2)][NO3] (2): triclinic, P1, a
      = 12.295(3) A, b = 13.295(3) A, c = 13.782(3) A, alpha = 89.105(17) degrees, beta
      = 66.096(18) degrees, gamma = 71.980(19) degrees, V = 1929.5(8) A3, Z = 2. These
      structures are the first reported examples of linear eta 2-acetonitrile
      coordination to any metal ion and the first structures illustrating eta 2
      acetonitrile and dichloromethane ligation to an alkali metal ion. Possible steric
      and electronic origins of these unusual metal-ligand interactions are discussed.

PMID- 12526467
TI  - Electronic effects on the rates of coupled two-electron/halide self-exchange
      reactions of substituted ruthenocenes.
AB  - The complexes (MemCp)(MenCp)Ru (m,n = 1,1; 0.4; 0.5; 1.5) have been synthesized
      along with the corresponding halometalloceniums [(MemCp)(MenCp)RuX]+ (X = Cl, Br,
      I). The two-electron/halide transfer self-exchange kinetics have been determined
      and compared to those of the Cp2Ru/[Cp2RuX]+ parent system. Methylation decreases
      the rate of exchange monotonically, and plots of ln(kex) vs number of methyl
      groups are linear for constant X. It is concluded that steric effects do not
      contribute significantly to the observed kinetics. Thermodynamic studies of
      halide substitution equilibria support the conclusion that the electronic effects
      of methylation are essentially additive.

PMID- 12526468
TI  - Solution and solid-state structures of phosphine adducts of monomeric zinc
      bisphenoxide complexes. Importance of these derivatives in CO2/epoxide
      copolymerization processes.
AB  - Phosphine derivatives of the monomeric zinc phenoxide complexes,
      (phenoxide)2ZnLn, where phenoxide equals 2,6-di-tert-butylphenoxide, 2,4,6-tri
      tert-butylphenoxide, and 2,6-diphenylphenoxide and n = 1 or 2, have been
      synthesized from the reaction of Zn[N(SiMe3)2]2 and the corresponding phenol
      followed by the addition of phosphine. The complexes have been characterized in
      solution by 31P NMR spectroscopy and in selected instances in the solid-state by
      X-ray crystallography. The small, basic phosphine, PMe3, provided the only case
      of an isolated complex possessing two phosphine ligands (i.e., n = 2). For all
      other larger phosphines only the monophosphine adducts were obtained.
      Furthermore, only fairly basic phosphines were found to bind to zinc, e.g.,
      whereas PPh3 (pKa = 2.73) was ineffective, PPh2Me (pKa = 4.57) did form a strong
      bond to zinc. The solid-state structures of the monophosphine adducts consist of
      a near-trigonal planar geometry about the zinc center, where the average P-Zn-O
      angles are larger than the O-Zn-O angles. On the other hand, the bisphosphine
      adduct, Zn(O-2,4,6-tBu3C6H2)(2).2PMe3, is a distorted tetrahedral structure with
      O-Zn-O and P-Zn-P bond angles of 108.8(2) degrees and 107.1(9) degrees,
      respectively. Competitive phosphine binding studies monitored by 31P NMR
      spectroscopy provided a relative binding order of PPh3 approximately PtBu3 <<
      PPh2Me < PCy3 < PMe2Ph < PnBu3 < PEt3 < PMe3. Hence, the relative binding of
      basic phosphine ligands at these congested zinc sites is largely determined by
      their steric requirements. All phosphine adducts, with the exception of PMe2Ph
      and PMe3, were found to undergo slow self-exchange (< 600 s-1) with free
      phosphine by 31P NMR spectroscopy. However, the two small phosphines, PMe2Ph
      (cone angle = 122 degrees) and PMe3 (cone angle = 118 degrees), were shown to
      undergo rapid exchange presumably via an associative mechanism. Although there
      was no kinetic preferences for PCy3 binding to cadmium vs zinc, cadmium was
      thermodynamically favored by about a factor of 2.5. The addition of up to 3 equiv
      of PCy3 to the Zn(O-2,6-tBu2C6H3)2 or Zn(O-2,4,6-tBu3C6H2)2 derivatives did not
      significantly alter the reactivity of these catalysts for the copolymerization of
      cyclohexene oxide (CHO) and CO2 to high-molecular weight poly(cyclohexene
      carbonate). However, the presence of PCy3 greatly retarded their ability to
      homopolymerize CHO to polyether or to afford polyether linkages during the
      copolymerization of CHO/CO2.

PMID- 12526469
TI  - Interactions between divalent metal ions and an octacoordinate macrocyclic
      ligand.
AB  - A dinucleating hexaazadiphenol macrocyclic ligand, 15,31-dimethyl
      3,11,19,27,33,35-hexaazapentacyclo[27.3.1.1.(5,9)1.(13,17)1.
      (21,25)]hexatriaconta-5,7,9(33),13,15,17(34),21,23,25(35),29,31,1(36)- dodecaene
      34,36-diol (H2L), forms a number of protonated, neutral, and/or hydroxo
      mononuclear, homodinuclear, and heterodinuclear complexes with the divalent metal
      ions Cu2+, Cd2+, Mn2+, and Zn2+, controlled by the stoichiometry of the metal ion
      and ligand as well as the pH values of the solution. Their stability constants
      and species distribution as a function of p[H] are determined. The pH
      potentiometric studies show that the dinuclear complexes are formed via the
      mononuclear chelates in which two kinds of coordination patterns are observed.
      One is that the metal ions are complexed by exactly half of coordination sites of
      the dinucleating macrocycle (N3O-), and the other is that the metal ions occupy
      salen-like sites of the macrocycle (N3O(2)2-). In the 2:1 systems (2:1 molar
      ratio of metal ion to ligand), the mononuclear species predominate in acidic
      solutions while the dinuclear species predominate in basic solutions, except for
      the case of copper. The protonated mononuclear complex [H2LZn](NO3)(2).5H2O forms
      triclinic crystals, of space group P1, with a = 10.7797(12) A, b = 10.9047(12) A,
      c = 17.0176(15) A, alpha = 106.857(9) degrees, beta = 95.822(8) degrees, gamma =
      100.191(9) degrees, and Z = 2; the neutral heterodinuclear complex
      [LZnCdCl2].6H2O forms monoclinic crystals, of space group C2/c, with a =
      16.234(5) A, b = 15.976(9) A, c = 29.829(11) A, alpha = 90 degrees, beta =
      90.28(2) degrees, gamma = 90 degrees, and Z = 8.

PMID- 12526470
TI  - New approach to Ru(II) pincer ligand chemistry. Bis(tert
      butylaminomethyl)pyridine coordinated to ruthenium(II).
AB  - Reaction of 2,6-bis-(tBuNHCH2)2NC5H3 ("N2py") with RuCl2(PPh3)3 gives two isomers
      of Ru(N2py)Cl2(PPh3), 5, while reaction with RuCl2(DMSO)4 (DMSO = Me2SO) gives
      isomerically pure Ru(N2py)Cl2(DMSO), whose structure is reported. The PPh3 of 5
      can be replaced by CO, P(OPh)3, or pyridine. The chlorides in Ru(N2py)Cl2(CO) can
      both be replaced by F3CSO3-. Isomer structure preferences are discussed, and the
      reaction of Ru(N2py)Cl2(pyridine) with O2 gives apparent oxidation of N2py to
      give the diimine.

PMID- 12526471
TI  - Sugar binding to VO3+. Synthesis and structure of a new mannopyranoside vanadate.

PMID- 12526472
TI  - A linear, four-spin Mn(II)-nitronyl-nitroxide-substituted phosphine oxide system
      exhibiting both antiferro- and ferromagnetic interactions.

PMID- 12526473
TI  - Synthesis of nanocrystalline CuMS2 (M = In or Ga) through a solvothermal process.

PMID- 12526474
TI  - An unusual metal-mediated formation of an asymmetrical carboxylate-bridged
      dinuclear copper(II) complex.

PMID- 12526475
TI  - Synthesis crystal structure and magnetic properties of the trinuclear nickel(II)
      complex bis[(mu-thiocyanato-N)bis(mu-pyridazine- N1,N2)bis(thiocyanato
      N)(pyridazine-N1)nickel(II)N,N1,N1]nickel(II).

PMID- 12526476
TI  - Synthesis of Cl2InN3, Br2InN3, and related adducts.

PMID- 12526477
TI  - The Mn(OESPz) (OESPz2- = 2,3,7,8,12,13,17,18-octakis(ethylsulfanyl)- 5,10,15,20
      tetraazaporphyrinato dianion) complex as an in situ regenerative defluorinating
      agent.

PMID- 12526478
TI  - A bibenzimidazole-containing ruthenium(II) complex acting as a cation-driven
      molecular switch.

PMID- 12526479
TI  - Guanidinium and imidazolium borates containing the first examples of an isolated
      nonaborate oxoanion: [B9O12(OH)6]3-.

PMID- 12526480
TI  - Synthesis, characterization, crystal structures, and reactions of trigonal
      bipyramidal tin(IV) complexes containing, a tetradentate tripodal
      tristhiolatophosphine ligand. Use in the one-step synthesis of an iron(IV)
      complex.

PMID- 12526482
TI  - Symmetry-lowering of the phthalocyanine chromophore by a C2 type axial ligand.

PMID- 12526481
TI  - Model for the cofactor formation reaction of E. coli ribonucleotide reductase.
      From a diiron(II) precursor to an FeIIIFeIV species via a peroxo intermediate.

PMID- 12526483
TI  - Programming the assembly of two- and three-dimensional architectures with DNA and
      nanoscale inorganic building blocks.
AB  - The use of biochemical molecular recognition principles for the assembly of
      nanoscale inorganic building blocks into macroscopic functional materials
      constitutes a new frontier in science. This article details efforts pertaining to
      the use of sequence-specific DNA hybridization events and novel inorganic surface
      coordination chemistry to control the formation of both two- and three
      dimensional functional architectures.

PMID- 12526485
TI  - Confined space synthesis. A novel route to nanosized zeolites.
AB  - Confined space synthesis is a novel method in zeolite synthesis. It involves
      crystallization of the zeolite inside the pore system of an inert mesoporous
      matrix. In this way it is possible to prepare nanosized zeolites with a
      controlled size distribution by proper choice of the inert matrix. Here, confined
      space synthesis was adopted to prepare nanosized ZSM-5, zeolite Beta, zeolite X,
      and zeolite A with tailored crystal size distributions using mesoporous carbon
      blacks as inert matrices. All zeolites were characterized by X-ray powder
      diffraction, transmission electron microscopy, and nitrogen adsorption/desorption
      prior to and after removal of the carbon matrix. ZSM-5 with Si/Al ratios of 50,
      100, and infinity (silicalite-1) were synthesized with controlled average crystal
      sizes in the range 20-75 nm. Nanosized zeolite Beta (7-30 nm), zeolite X (22-60
      nm), and zeolite A (25-37 nm) were prepared similarly. Removal of the carbon
      matrix by controlled combustion allows a convenient method for isolation of the
      pure and highly crystalline zeolites. Therefore, confined space synthesis appears
      to be an attractive method for preparation of zeolites with a controlled size
      distribution.

PMID- 12526484
TI  - Control of oxo-molybdenum reduction and ionization potentials by dithiolate
      donors.
AB  - The compounds (L-N3)MoO(qdt) and (L-N3)MoO(tdt) [(L-N3) = hydrotris(3,5-dimethyl
      1-pyrazolyl)borate; tdt = toluene-3,4-dithiolate; qdt = quinoxaline-2,3
      dithiolate] have been studied by cyclic voltammetry and photoelectron, magnetic
      circular dichroism, and electronic absorption spectroscopies, and the
      experimental data have been interpreted in the context of ab initio molecular
      orbital calculations on a variety of dithiolate dianion ligands. The PES data
      reveal very substantial differences between (L-N3)MoO(qdt) and (L-N3)MoO(tdt) in
      that the first ionization (originating from the Mo dxy orbital) for (L
      N3)MoO(qdt) is about 0.8 eV to deeper binding energy than that of (L-N3)MoO(tdt).
      This stabilizing effect is also reflected in the solution reduction potentials,
      where (L-N3)MoO(qdt) is approximately 220 mV easier to reduce than (L
      N3)MoO(tdt). A direct correlation between the relative donating ability of a
      given dithiolate ligand and the reduction potential of the (L-N3)MoO(dithiolate)
      complex has been observed, and a linear relationship exists between the
      calculated Mulliken charge on the S atoms of the dithiolate dianion and the Mo
      reduction potential. The study confirms previously communicated work (Helton, M.
      E.; Kirk, M. L. Inorg. Chem. 1999, 38, 4384-4385) that suggests that anisotropic
      covalency contributions involving only the out-of-plane S orbitals of the
      coordinated dithiolate control the Mo reduction potential by modulating the
      effective nuclear charge of the metal, and this has direct relevance to
      understanding the mechanism of ferricyanide inhibition in sulfite oxidase.
      Furthermore, these results indicate that partially oxidized pyranopterins may
      play a role in facilitating electron and/or atom transfer in certain pyranopterin
      tungsten enzymes which catalyze formal oxygen atom transfer reactions at
      considerably lower potentials.

PMID- 12526486
TI  - Formation of a novel trinuclear spirostannoxane tin(IV) compound. Crystal and
      molecular structure of [Sn(nBu)(Cl)[(OCH2CH2S)2Sn(nBu)]2] and the stannolane
      [(nBu)Sn(SCH2CH2O)SCH2CH2OH].
AB  - The reaction of nBuSnCl3 and the sodium salt of 2-mercaptoethanol (1:1) in
      ethanol gave the compound Sn(nBu)(Cl)[(OCH2CH2S)2Sn(nBu)]2 (1).
      [(nBu)Sn(SCH2CH2O)SCH2CH2OH] (2) was initially isolated from the reaction of 1
      with nBuMgCl as a rearrangement product but was also synthesized from nBuSn(O)OH
      and two molar equivalents of 2-mercaptoethanol. Both compounds were characterized
      by means of IR, 119Sn, 13C, and 1H NMR, FAB mass spectroscopy, and elemental
      analyses. The structures were determined by single-crystal X-ray diffraction. 1
      crystallizes in the monoclinic Cc space group (a = 18.492(3) A, b = 17.329(2) A,
      c = 10.787(1) A, beta = 111.88(1) degrees, Z = 4), while 2 crystallizes in the
      orthorhombic Pbca space group (a = 14.458(2) A, b = 10.393(1) A, c = 16.479(2) A,
      Z = 8). 1 is a trimetallic Tin(IV) compound in which the central atom is in 6
      fold coordination, while the two remaining tin atoms show 5-fold coordination.
      Both pentacoordinated tin atoms are bonded to a butyl group and to the oxygen and
      the sulfur atoms from two [OCH2CH2S]2- ligands forming two stannolanes, which are
      fused with the hexacoordinated tin atom forming a distannoxane system. This
      arrangement is quite different from previous ladder or staircase structures. NMR
      data point to maintenance of this structure in solution. 2 consists of
      [(nBu)Sn(SCH2CH2O)(SCH2CH2OH)] units, which are associated via intermolecular Sn
      O interactions building up a dimer. The tin atom forms two "stannolane" units by
      interaction with [OCH2CH2S]2- and [HOCH2CH2S]- ligands.

PMID- 12526487
TI  - Crystal structure and optical spectroscopy of Er2[Pt(CN)4]3.21H2O and
      Er2[Pt(CN)4]2.SO4.11.5H2O.
AB  - We have synthesized two forms of erbium tetracyanoplatinates, Er2[Pt(CN)4]3.21H2O
      (red form) and Er2[Pt(CN)4]2.SO4.11.5H2O (yellow form), and determined their
      crystal structures by X-ray diffraction. While the red form crystallizes in the
      orthorhombic space group Pbcn, with a = 15.4848(3) A, b = 13.8186(2) A, c =
      19.07820(10) A, alpha = beta = gamma = 90 degrees, and Z = 4, the yellow form
      precipitates in the tetragonal space group I4cm, with a = b = 14.321(2) A, c =
      13.338(3) A, alpha = beta = gamma = 90 degrees, and Z = 4. Both forms show
      [Pt(CN)4]2- chains but differ markedly in color and morphology. This is due to
      the incorporation of sulfate ions in the latter modification, leading to an
      increased Pt-Pt distance. The observed optical absorption and emission behavior
      of the title compounds is correlated with the Pt-Pt distances.

PMID- 12526489
TI  - Self-assembly of palladium(II) and platinum(II) complexes of 2-hydroxypyrimidine
      to novel metallacalix[4]arenes. Receptor properties through multiple H-bonding
      interactions.
AB  - Reaction of [enM(H2O)2](NO3)2 (en = ethylenediamine, M = PdII, PtII) with 2
      hydroxypyrimidine (Hpymo) in water results in self-assembly to cyclic complexes
      of type [enM(pymo-N1,N3)]4(NO3)4 (1, M = PdII; 2, M = PtII) which are
      structurally analogous to calix[4]arenes. The tetranuclear cations in compounds 1
      and 2 adopt, in the solid state, a 1,3-alternate orientation of the pymo
      residues. Attempts to coordinate either soft (PdII, PtII), borderline (CuII,
      ZnII), or hard (LaIII, BeII, NaI) metal ions to the oxo surface of the
      metallacalix[4]arene lower rim were fruitless. In fact, X-ray studies performed
      on [[enPt(pymo-N1,N3)]4(ClO4)4]2.[Cu(H2O)6](ClO4)2.9H2O (4) showed that multiple
      H-bonding interactions between the water coordination sphere of the copper center
      and the oxo surface of two tetranuclear cations take place instead of a direct
      interaction between the heterometal and the oxo surface of the
      metallacalix[4]arene. Encapsulation of [Cu(H2O)6]2+ is also responsible for the
      stabilization of the pinched-cone conformation of the tetranuclear cations in 4.
      pH* dependent 1H NMR spectra of compounds 1 and 2 indicate a very low basicity of
      the O-donor group of the pymo residues, revealing no protonation of this position
      down to pH* 0. Moreover, recrystallization of 2 from strongly acidic aqueous
      solution (approximately 1 M HClO4) affords the adduct [[enPt(pymo
      N1,N3)]4(ClO4)4]2.[H20O8](ClO4)4 (6). Analogously to 4, the cationic [H20O8]4+
      species is sandwiched between two tetranuclear cations as a result of multiple H
      bonding interactions with the oxo surface of two metallacalix[4]arenes. Again a
      pinched-cone orientation of the pymo residues is realized.

PMID- 12526488
TI  - A controlled NO-releasing compound: synthesis, molecular structure, spectroscopy,
      electrochemistry, and chemical reactivity of R,R,S,S-trans
      [RuCl(NO)(cyclam)]2+(1,4,8,11-tetraazacyclotetradecane).
AB  - The synthesis of trans-[RuCl(NO)(cyclam)]2+ (cyclam = 1,4,8,11
      tetraazacyclotetradecane) can be accomplished by either the addition of cyclam to
      K2[RuCl5NO] or by the addition of NO to trans-[RuCl(CF3SO3)(cyclam)](CF3-SO3).
      Crystals of trans-[RuCl(NO)(cyclam)](ClO4)2 form in the monoclinic space group
      P2(1)/c, with unit cell parameters of a = 7.66500(2) A, b = 24.7244(1) A, c =
      16.2871(2) A, beta = 95.2550(10) degrees, and Z = 4. One of the two independent
      molecules in the unit cell lies disordered on a center of symmetry. For the ion
      in the general position, the Ru-N and N-O bond distances and the [Ru-N-O]3+ bond
      angle are 1.747(4) A, 1.128(5) A, 178.0(4) degrees, respectively. In both ions,
      cyclam adopts the (R,R,S,S) configuration, which is also consistent with 2D COSY
      1H NMR studies in aqueous solution. Reduction (E degree = -0.1 V) results in the
      rapid loss of Cl- by first-order kinetics with k = 1.5 s-1 and the slower loss of
      NO (k = 6.10 x 10(-4) s-1, delta H++ = 15.3 kcal mol-1, delta S++ = -21.8 cal mol
      1 K-1). The slow release of NO following reduction causes trans
      [RuCl(NO)(cyclam)]2+ to be a promising controlled-release NO prodrug for
      vasodilation and other purposes. Unlike the related complex trans
      [Ru(NO)(NH3)4(P(OEt)3)](PF6)2, trans-[RuCl(NO)(cyclam)]Cl2 is inactive in
      modulating evoked potentials recorded from mice hippocampal slices probably
      because of the slower dissociation of NO following reduction.

PMID- 12526490
TI  - Metallocyclopeptide complexes with MII(S.Cys)4 chromophores.
AB  - The tetracysteinyl peptide cyclo[Lys1,12](Gln-Cys-Gly-Val-Cys-Gly-Lys-Cys-Ile-Ala
      Cys-Lys) ([symbol: see text] L(Cys.SH)4) was synthesized by solid-phase methods
      using an Fmoc/t-Bu/allyl strategy on a PAL-PEG-PS support. The formation of the
      1:1 complexes with M = Fe2+, Co2+, and Ni2+ was observed by spectrophotometric
      monitoring of reactions in aqueous solution at pH 7.5. Size exclusion
      chromatography indicated that the peptide is a monomer and the complexes are
      dimers [M2([symbol: see text]L(Cys.S)4)2] in aqueous buffer at pH 7.5. Cobalt and
      nickel K-edge X-ray absorption data and EXAFS analysis of [Co2([symbol: see text]
      L(Cys.S)4)2] and [Ni2([symbol: see text] L(Cys.S)4)2] as lyophilized solids are
      reported. Derived bond distances are Co-S = 2.30 A and Ni-S = 2.21 A. From the
      collective results provided by absorption spectra, K-edges, EXAFS, and bond
      length comparisons with known structures, it is shown that [Fe2([symbol: see
      text] L(Cys.S)4)2] and [Co2([symbol: see text] L(Cys.S)4)2] possess distorted
      tetrahedral structures and [Ni2([symbol: see text] L(Cys.S)4)2] has distorted
      square planar stereochemistry. The Co(II) chromophore is particularly distinctive
      of the assigned structure, displaying three components of the parent tetrahedral
      ligand field transition 4A2-->4T1(P) (610, 685, 740 nm). The observed structures
      conform to the intrinsic stereochemical preferences of the metal ions. Structures
      for the binuclear complexes are suggested. These are the first characterized
      metal complexes of a cysteinyl cyclopeptide and among the few well-documented
      complexes of synthetic cyclopeptides. This study is a desirable first step in the
      design of cyclic peptides for the binding of mononuclear and polynuclear metal
      centers.

PMID- 12526491
TI  - Theoretical studies of molybdenum peroxo complexes [MoOn(O2)3-n(OPH3)] as
      catalysts for olefin epoxidation.
AB  - The equilibrium geometries of the molybdenum oxo/peroxo compounds MoOn(O2)3-n and
      the related complexes [MoOn(O2)3-n(OPH3)] and [MoOn(O2)3-n(OPH3)(H2O)] (n = 0-3)
      have been calculated using gradient-corrected density-functional theory at the
      B3LYP level. The structures of the peroxo complexes with ethylene ligands
      [MoOn(O2)3-n(C2H4)] and [MoOn(O2)3-n(OPH3)(C2H4)] (n = 1, 2) where ethylene is
      directly bonded to the metal have also been optimized. Calculations of the metal
      ligand bond-dissociation energies show that the OPH3 ligand in [MoOn(O2)3
      n(OPH3)] is much more strongly bound than the ethylene ligand in [MoOn(O2)3
      n(C2H4)]. This makes the substitution of phosphane oxide by olefins in the
      epoxidation reaction unlikely. An energy-minimum structure is found for
      [MoO(O2)2(OPH3)(C2H4)], for which the dissociation of C2H4 is exothermic with D0
      = -5.2 kcal/mol. The reaction energies for the perhydrolysis of the oxo complexes
      with H2O2 and the epoxidation of ethylene by the peroxo complexes have also been
      calculated. The peculiar stability of the diperoxo complex [MoO(O2)2(OPH3)(H2O)]
      can be explained with the reaction energies for the perhydrolysis of [MoOn(O2)3
      n(OPH3)(H2O)]. The first perhydrolysis step yielding the monoperoxo complex is
      less exothermic than the second perhydrolysis reaction, but the further reaction
      with H2O2 yielding the unknown triperoxo complex is clearly endothermic. CDA
      analysis of the metal-ethylene bond shows that the binding interactions are
      mainly caused by charge donation from the ligand to the metal.

PMID- 12526492
TI  - Ruthenium bisbipyridine complexes of horse heart cytochrome c: characterization
      and comparative intramolecular electron-transfer rates determined by pulse
      radiolysis and flash photolysis.
AB  - The reaction of [Ru(bpy)2L(H2O)]2+ (bpy = 2,2'-bipyridine, L = imidazole, water)
      with reduced horse heart cytochrome c results in coordination of [RuII(bpy)2L] at
      the His 33 and His 26 sites. Coordination at the His 33 site gave a
      diastereomeric [RuII(bpy)2L]-His-cyt c(II) mixture favoring the lambda-Ru form
      regardless of the substituent on the bipyridine ligands, while substitution at
      the more buried His 26 site gave an isomeric distribution that varies according
      to the substituent on the bipyridine ligands. The diastereomeric aquoproteins (L
      = H2O) are distinguished by their redox potentials and their conversion to the
      corresponding fluorescent imidazole proteins. Intramolecular electron transfer
      between the reduced ruthenium bipyridine and cyt c(III) in [RuII(bpy.)(bpy)L]
      His33-cyt c(III) was determined by reductive pulse radiolysis using the aqueous
      electron as a reducing agent, kret = (2.0 +/- 0.3) x 10(5) s-1, and kret is
      independent of the sixth ligand L = H2O, imidazole. In addition, the rate
      constant for intramolecular electron transfer from cyt c(II) to the
      ruthenium(III) center in [RuIII(bpy)2L]-His33-cyt c(II) was determined by
      oxidative pulse radiolysis using azide and carbonate radicals. This rate is very
      sensitive to the nature of the sixth ligand. When L = H2O, the intramolecular
      electron-transfer rate for the major diastereomer lambda-cis-[RuIII (bpy)2(H2O)]
      His33-cyt c(II) is k = 1.1 x 10(4) s-1 and is independent of pH between 5.6 and
      8.3. The minor delta-cis-[RuIII(bpy)2(H2O)]-His33-cyt c(II) isomer has pH
      dependent electrochemistry and a lower rate of intramolecular electron transfer.
      Complete conversion from L = H2O to L = imidazole is slow, requiring more than 7
      days in 1 M imidazole. A lower limit (k > 2 x 10(6) s-1) for the intramolecular
      electron-transfer rate constant in [RuIII(bpy)2(L)]-His33-cyt c(II), L =
      imidazole, could be obtained by pulse radiolysis in the absence of the slower
      reacting aquo species. This observation is in agreement with the value of 3 x
      10(6) s-1 measured by flash photolysis. Earlier pulse radiolysis experiments
      primarily measured the aquoligated ruthenium protein, while the flash photolysis
      experiments measured the imidazole-ligated fraction because it is the only
      species oxidatively quenched in the photoinduced reactions. Intramolecular
      electron-transfer reactions for a new series of ruthenium bipyridine complexes,
      [Ru(dabpy)2L]-His33-cyt c proteins (dabpy = 4,4'-diamino-2,2'-bipyridine) (L =
      imidazole, pyridine, isonicotinamide and pyrazine), proceed with lower driving
      force, resulting in slower rate constants amenable to measurement by oxidative
      pulse radiolysis. The electron-transfer rate constants for this series spanned a
      wide range of the Marcus log k vs delta G plot.

PMID- 12526493
TI  - A novel alpha-helix-liked metallohelicate series and their structural adjustments
      for the isomorphous substitution.
AB  - A novel metallohelical motif is well designed and synthesized by mimicking the
      alpha-helical fold structure of protein. The 1D helical structures of
      [Cd(CH2(COO)2)(SC(NH2)2)2]n (I) and [Zn(CH2(COO)2) (SC(NH2)2)2]n (II) are
      primarily induced and stabilized by the multiple long-range intrahelix hydrogen
      bonds. Malonate dianion acts as a bidentate ligand coordinated with metal ions to
      form the backbone of the helix, and thiourea molecules that bend into the helical
      turn are involved in the intrahelix hydrogen-bond system. The metal ion
      occupations in the helix of I and II can be freely substituted by simply
      controlling the initial ratio of those two metal ions. Single crystals of three
      mixed metal ion complexes of [Cd0.77Zn0.23(CH2(COO)2)(SC(NH2)2)2]n (III),
      [Cd0.50Zn0.50(CH2(COO)2)(SC(NH2)2)2]n (IV), and
      [Cd0.21Zn0.79(CH2(COO)2)(SC(NH2)2)2]n (V) were synthesized from systems with an
      initial Cd/Zn mole ratio of 1:1 for III, 1:2 for IV, and 1:8 for V. They are
      isomorphous as confirmed by X-ray characterization. When the metal ion is
      substituted, the multiple intrahelix hydrogen interaction motifs of the
      coordination polymer structure are self-adjusted to sustain their 1D helical
      motifs.

PMID- 12526494
TI  - Cs3AgAs4Se8 and CsAgAs2Se4: selenoarsenates with infinite 1 infinity[AsSe2]-
      chains in different Ag+ coordination environments.
AB  - Two quaternary silver selenoarsenates Cs3AgAs4Se8 (I) and CsAgAs2Se4 (II) have
      been discovered by methanothermal reaction of Li3AsSe3 with AgBF4 in the presence
      of the respective alkali metal sources Cs2CO3 and CsCl. Orange crystals of
      Cs3AgAs4Se8 (I) were formed after reaction at 120 degrees C for 72 h, whereas red
      CsAgAs2Se4 (II) was obtained under slightly different conditions at 140 degrees C
      for 70 h. Both compounds possess novel two-dimensional (2D) polyanions consisting
      of infinite 1 infinity[AsSe2]- chains that are interconnected by Ag+ ions in
      different coordination patterns. In I, a double layer of 1 infinity[AsSe2]-
      chains is bridged by distorted trigonal planar coordinated Ag+ atoms to form a 2
      infinity[AgAs4Se8]3- layer with a thickness of about 11.3 A. The nonbonding
      Ag...Ag distances are about 4.220 A, and large cavities within the layers
      accommodate for three of the four crystallographic Cs+ cations. The double amount
      of Ag+ atoms per AsSe2 chain unit in II leads to simple layers 2
      infinity[AgAs2Se4]- [=[Ag2As4Se8]2-] in which the Ag+ atoms are arranged in rows
      between the 1 infinity[AsSe2]- chains, with alternating Ag...Ag distances of
      3.053(3) and 3.488(3) A. Hereby the 1 infinity[AsSe2]- polyanions show a disorder
      within the central (-As-Seb)- chain (b = bridging), while the positions of the
      terminal Se atoms (Set) remain unaffected. The thermal, optical, and
      spectroscopic properties of the compounds are reported. Both I and II melt with
      decomposition and are wide band gap semiconductors with values of 2.07 and 1.79
      eV, respectively. Raman spectroscopic data show typical band patterns expected
      for infinite [AsSe2]- chains. Crystal Data: Cs3AgAs4Se8 (I), monoclinic, C2/c, a
      = 25.212(2) A, b = 8.0748(7) A, c = 22.803(2) A, beta = 116.272(2) degrees, Z =
      8; CsAgAs2Se4 (II), monoclinic, P2(1)/n, a = 10.9211(1) A, b = 6.5188(2) A, c =
      13.7553(3) A, beta = 108.956(1) degrees, Z = 4.

PMID- 12526495
TI  - Addition and metathesis reactions of zirconium and hafnium imido complexes.
AB  - The zirconium and hafnium imido metalloporphyrin complexes (TTP)M = NArtPr (TTP =
      meso-5,10,15,20-tetra-p-tolylporphyrinato dianion; M = Zr (1), Hf; AriPr = 2,6
      diisopropylphenyl) were used to mediate addition reactions of carbonyl species
      and metathesis of nitroso compounds. The imido complexes react in a stepwise
      manner in the presence of 2 equiv of pinacolone to form the enediolate products
      (TTP)M[OC(tBu)CHC(tBu)(Me)O] (M = Zr (2), Hf (3)), with elimination of H2NAriPr.
      The bis(mu-oxo) complex [(TTP)ZrO]2 (4) is formed upon reaction of (TTP)Zr =
      NAriPr with PhNO. Treatment of compound 4 with water or treatment of compound 2
      with acetone produced the (mu-oxo)bis(mu-hydroxo)-bridged dimer [(TTP)Zr]2(mu
      O)(mu-OH)2 (5). Compounds 2, 4, and 5 were structurally characterized by single
      crystal X-ray diffraction.

PMID- 12526496
TI  - Nitric oxide binding to ferric cytochrome P450: a computational study.
AB  - The interaction between nitric oxide (NO) and the active site of ferric
      cytochrome P450 was studied by means of density functional theory (DFT), at the
      generalized gradient approximation level, and of the SAM1 semiempirical method.
      The electrostatic effects of the protein environment were included in our DFT
      scheme by using a hybrid quantum classical approach. The active-site model
      consisted of an iron(III) porphyrin, the adjacent cysteine residue, and one
      coordinated water molecule. For this system, spin populations and relative
      energies for selected spin states were computed. Interestingly, the unpaired
      electron density, the HOMO, and the LUMO were found to be highly localized on the
      iron and in an appreciable extent on the sulfur coordinated to the metal. This
      provides central information about the reactivity of nitric oxide with the active
      site. Since the substitution of a molecule of H2O by NO has been proposed as
      being responsible for the inhibition of the cytochrome in the presence of nitric
      oxide, we have analyzed the thermodynamic feasibility of the ligand exchange
      process. The structure of the nitrosylated active site was partially optimized
      using SAM1. A low-spin ground state was obtained for the nitrosyl complex, with a
      linear Fe-N-O angle. The trends found in Fe-N-O angles and Fe-N lengths of the
      higher energy spin states provided a notable insight into the electronic
      configuration of the complex within the framework of the Enemark and Feltham
      formalism. In relation to the protein environment, it was assessed that the
      electrostatic field has significant effects on several computed properties.
      However, in both vacuum and protein environments, the ligand exchange reaction
      turned out to be exergonic and the relative orders of spin states of the relevant
      species were the same.

PMID- 12526497
TI  - Experimental electron density analysis of Mn2(CO)10: metal-metal and metal-ligand
      bond characterization.
AB  - The experimental electron density rho(r) of Mn2(CO)10 was determined by a
      multipole analysis of accurate X-ray diffraction data at 120 K. The quantum
      theory of atoms in molecules (QTAM) was applied to rho(r) and its Laplacian
      [symbol: see text] 2 rho(r). The QTAM analysis of rho(r) showed the presence of a
      bond critical point (rc); its associated bond path connects the two Mn atoms, but
      no cross interaction line was found between one manganese and the equatorial
      carbonyls of the other. The distribution of [symbol: see text] 2 rho(r) indicated
      "closed-shell" interactions for the metallic Mn-Mn bond and the dative Mn-CO
      bonds. The values of the topological parameters of the density at rc, rho(rc),
      [symbol: see text] 2 rho(rc), G(rc) (kinetic energy density), and V(rc)
      (potential energy density), characterize the bonds and are intermediate to those
      corresponding to typical ionic and covalent bonds.

PMID- 12526499
TI  - Synthesis and characterization of calcium complexes containing eta 2-pyrazolato
      ligands.
AB  - Treatment of calcium bromide with 3,5-di-tert-butylpyrazolatopotassium (2 equiv)
      in tetrahydrofuran afforded Ca(tBu2pz)2(THF)2 (69%). The reaction of this
      compound with pyridine (3 equiv), tetramethylethylenediamine (TMEDA, 1 equiv),
      N,N,N',N',N"-pentamethyldiethylenetriamine (PMDETA, 1 equiv), triglyme (1 equiv),
      and tetraglyme (1 equiv) yielded Ca(tBu2pz)2(py)3 (51%), Ca(tBu2pz)2(TMEDA)
      (74%), Ca(tBu2pz)2(PMDETA) (50%), Ca(tBu2pz)2(triglyme) (73%), and
      Ca(tBu2pz)2(tetraglyme) (57%), respectively. Treatment of the tetrahydrofuran
      adduct of Ca(Me2pz)2, generated in situ, with PMDETA (1 equiv), triglyme (1
      equiv), and tetraglyme (1 equiv) afforded Ca(Me2pz)2(PMDETA) (65%),
      Ca(Me2pz)2(triglyme) (54%), and Ca(Me2pz)2(tetraglyme) (40%), respectively. The X
      ray crystal structures of Ca(tBu2pz)2(py)3, Ca(tBu2pz)2(TMEDA),
      Ca(tBu2pz)2(PMDETA), Ca(tBu2pz)2(triglyme), and Ca(Me2pz)2(PMDETA) revealed six-,
      seven-, or eight-coordinate calcium centers with eta 2-pyrazolato ligands.
      Ca(tBu2pz)2(triglyme) sublimes at 160 degrees C (0.1 mmHg). The potential utility
      of these complexes as source compounds for chemical vapor deposition processes is
      discussed.

PMID- 12526498
TI  - Synthesis and characterization of the dimethyl-substituted bisbenzimidazole
      ligand and its manganese complex.
AB  - Macrocycles with unique properties provide new avenues for the design of novel
      catalysts and materials. Here, we report, for the first time, the synthesis and
      characterization of the dimethyl-substituted bisbenzimidazole ligand (Me2BBZ) and
      its manganese complex (Mn-Me2BBZ). The Me2BBZ ligand is similar to porphyrin and
      phthalocyanine macrocycles in terms of its cavity size and metal-binding mode,
      but owing to electronic and charge differences, it exhibits properties that make
      it distinct from its structural counterparts. For instance, the optical spectra
      of bisbenzimidazoles lack transitions in the 500-900 nm region. Perhaps the most
      significant feature of the Me2BBZ ligand, however, is its inherent nonplanarity.
      Geometric restraints within this nonplanar ligand give rise to two atropisomers,
      which, when separated, could have potential in chiral catalysis and recognition.
      In addition, here we show that this nonplanarity can help to promote unusual
      crystal-packing interactions. Within the structure of the Mn-Me2BBZ complex,
      intermolecular pi-stacking interactions of the phenyl and benzimidazole groups
      lead to the formation of a distinct two-dimensional "staircase" lattice comprised
      of alternating Mn-Me2BBZ atropisomers. The potential significance of this
      structural arrangement is revealed by temperature-dependent magnetic studies that
      indicate weak antiferromagnetic coupling between the metal ions in the crystal.
      Fine-tuning of these long-range electronic and magnetic interactions could be
      useful for the design of novel molecular materials.

PMID- 12526500
TI  - Controlling substitution chemistry in ruthenium(II) systems. Synthesis of
      heteroleptic complexes incorporating the [Ru([9]aneS3)]2+ metal center.
AB  - The complex [Ru(py)3([9]aneS3)][PF6]2, 1 (py = pyridine), has proved to be a
      suitable starting material for the synthesis of heteroleptic Ru(II) complexes. By
      exploiting unfavorable steric interactions between 2-H and 6-H hydrogens of
      coordinated pyridyl ligands, we have synthesized half-sandwich complexes
      incorporating the thiocrown [9]aneS3 and a variety of facially coordinated N
      donor ligands. Such complexes are easily prepared: Stirring 1 at room temperature
      in the presence of a suitable nitrile ligand leads to the exclusive substitution
      of one py ligand to produce complexes such as [([9]aneS3)Ru(py)2(NCMe)][PF6]2, 2.
      However, if the same reaction is carried out at higher temperatures, two py
      ligands are substituted, leading to complexes such as
      [([9]aneS3)Ru(py)(NCMe)2][PF6]2, 3. An alternative approach to such heteroleptic
      species has also been developed which exploits the restricted ability of
      thioethers to neutralize positive charges through sigma-donation. This phenomenon
      allows the synthesis of heteroleptic complexes in a two-step procedure via
      monocationic species. By variation of the donor/acceptor properties of ligands
      incorporated into the [Ru([9]aneS3)]2+ metal center, it is possible to tune the
      Ru(III)/Ru(II) redox couple over a range of > 700 mV. The solid-state structures
      of 1-3 were confirmed by X-ray crystallography studies. Crystal data:
      C22H30F12N4O2P2RuS3 (1.CH3NO2), monoclinic, Cc, a = 23.267(5) A, b = 11.5457(18)
      A, c = 26.192(5) A, alpha = 90 degrees, beta = 114.836(10) degrees, gamma = 90
      degrees, Z = 8; C18H25F12N3P2RuS3 (2), triclinic, P1, a = 11.3958(19) A, b =
      11.4280(19) A, c = 11.930(2) A, alpha = 100.518(3) degrees, beta = 100.542(3)
      degrees, gamma = 112,493(3) degrees, Z = 2; C15H23F12N3P2RuS3 (3), orthorhombic,
      Pna2(1)), a = 14.748(5) A, b = 18.037(18) A, c = 10.341(5) A, alpha = 90 degrees,
      beta = 90 degrees, gamma = 90 degrees, Z = 4.

PMID- 12526501
TI  - Solid-state synthesis and characterization of novel aluminophosphates, A3Al2P3O12
      (A = Na, K, Rb, Tl): influence of A+ ions on the coordination of aluminum.
AB  - Four aluminophosphates, A3Al2P3O12 (A = Na, K (1), Rb (2), Tl (3)), have been
      synthesized by solid-state reactions and characterized by X-ray diffraction and
      NMR and IR spectroscopic techniques. Aluminum has trigonal bipyramidal
      coordination in the thallium compound and tetrahedral coordination in the others.
      Potassium, rubidium and thallium analogues have been structurally characterized
      by single-crystal X-ray diffraction and found to possess three-dimensional
      (Al2P3O12)3- anionic frameworks with channels occupied by A+ countercations.
      These frameworks are built from corner connections of PO4 tetrahedra with AlO4
      tetrahedra in 1 and 2 and with AlO5 trigonal bipyramids in 3. Pertinent crystal
      data are as follows: for 1, orthorhombic space group Pna2(1), a = 8.685(2) A, b =
      16.947(2) A, c = 8.458(3) A, Z = 4; for 2, orthorhombic space group Cmc2(1), a =
      17.164(2) A, b = 8.6270(6) A, c = 8.8140(14) A, Z = 4; for 3, orthorhombic space
      group Pna2(1), a = 6.1478(15) A, b = 10.396(3) A, c = 17.787(5) A, Z = 4.
      Compound 3 is a rare example of an oxide possessing aluminum exclusively in
      trigonal bipyramidal coordination.

PMID- 12526502
TI  - Syntheses, structures, and fluxionality of blue luminescent zinc(II) complexes:
      Zn(2,2',2"-tpa)Cl2, Zn(2,2',2"-tpa)2(O2CCF3)2, and Zn(2,2',3"-tpa)4(O2CCF3)2 (tpa
      = tripyridylamine).
AB  - Three novel Zn(II) complexes containing either 2,2',2"-tripyridylamine (2,2',2"
      tpa) or 2,2',3"-tripyridylamine (2,2',3"-tpa) have been synthesized and
      structurally characterized. Compound 1, Zn(2,2',2"-tpa)Cl2, has a tetrahedral
      geometry while compounds 2, Zn(2,2',2"-tpa)2(O2CCF3)2, and 3, Zn(2,2',3"
      tpa)4(O2CCF3)2, have an octahedral geometry. The 2,2',2"-tpa ligand in 1 and 2
      functions as a bidentate ligand, chelating to the zinc center, while the 2,2",3"
      tpa ligand in 3 functions as a terminal ligand, binding to the zinc center
      through the 3-pyridyl nitrogen atom. All three compounds emit a blue color in
      solution and in the solid state. The emission maxima for the three compounds in
      solution are at lambda = 422, 426, and 432 nm, respectively. The blue
      luminescence of the complexes is due to a pi *-->pi transition of the tpa ligand
      as established by an ab initio calculation on the free ligand 2,2',2"-tpa and
      complex 1. Compounds 1 and 2 are fluxional in solution owing to an exchange
      process between the coordinate and noncoordinate 2-pyridyl rings of the 2,2',2"
      tpa ligand. Compound 2 is also fluxional owing to a cis-trans isomerization
      process, as determined by variable-temperature 1H NMR spectroscopic analysis.

PMID- 12526503
TI  - Synthesis and characterization of four ethylenediamine-templated iron arsenates.
AB  - Four new ethylenediamine-templated iron arsenates and fluoroarsenates have been
      hydrothermally synthesized from iron metal, hydrofluoric and arsenic acids, and
      ethylenediamine. Fe(H2AsO4)(HAsO4)2.enH2.H2O (1) is one-dimensional and contains
      chains, FeIIIFeIIF2(HAsO4)(AsO4).enH2.2H2O (2) is a layered fluoroarsenate, and
      Fe3(HAsO4)6.enH2.NH3.NH4 (3) and Fe2F2(AsO4)2(H2O).enH2 (4) are an arsenate and a
      fluoroarsenate, respectively, with three-dimensional open-framework type
      structures. Compounds 1, 3, and 4 contain Fe(III) only, while 2 is a mixed
      valence compound of Fe(III) and Fe(II). The structures were determined from
      single-crystal X-ray diffraction. Crystal data: (1) P2(1), a = 4.762(1) A, b =
      16.086(3) A, c = 8.698(2) A, beta = 90.65(3) degrees, Z = 2; (2) P-1, a =
      5.289(1) A, b = 7.573 (1) A, c = 8.888(2) A, alpha = 67.32(3) degrees, beta =
      82.77(3) degrees, gamma = 69.76(3) degrees, Z = 1; (3) C2/c, a = 18.384(3) A, b =
      8.785(1) A, c = 16.052(2) A, beta = 111.11(1) degrees, Z = 4; (4) Pbca, a =
      10.490(2) A, b = 10.090(2) A, c = 20.540(4) A, Z = 8. Strong hydrogen bonding
      exists between the chains and the layers in 1 and 2, and between the diprotonated
      ethylenediamine and the inorganic part of the structures of 1, 2, and 4. The
      ethylenediamine in 3 is not hydrogen bonded, and as a result it is disordered.
      The compounds are characterized also by thermogravimetric analysis, infrared
      spectroscopy, elemental analysis, and magnetic measurements.

PMID- 12526504
TI  - Magnetic ordering and spin-glass behavior in first-row transition metal
      hexacyanomanganate(IV) Prussian blue analogues.
AB  - Magnetically ordered Prussian blue analogues with the general formulation of
      M[Mn(CN)6] (M = V, Cr, Mn, Co, Ni) were made in aprotic media utilizing
      [MnIV(CN)6]2-. These analogs are valence-ambiguous, as they can be formulated as
      MII[MnIV(CN)6] or MIII[MnIII(CN)6]. The X-ray powder diffraction of each member
      of this family can be indexed to the face-centered cubic (fcc) Prussian blue
      structure type, with atypically reduced unit cell parameters (a approximately
      9.25 +/- 0.25 A) with respect to hydrated Prussian blue structured materials (a >
      or = 10.1 A). The reduced a-values are attributed to a contraction of the lattice
      in the absence of water or coordinating solvent molecule (i.e., MeCN) that is
      necessary to help stabilize the structure during lattice formation. Based on vCN
      IR absorptions, X-ray photoelectron spectra, and magnetic data, the following
      oxidation state assignments are made: MII[MnIV(CN)6] (M = Co, Ni) and
      MIII[MnIII(CN)6] (M = V, Cr, Mn). Formation of MnIII[MnIII(CN)6] is in contrast
      to MnII[MnIV(CN)6] prepared from aqueous media. Above 250 K, the magnetic
      susceptibilities of M[Mn(CN)6] (M = V, Cr, Mn, Co, Ni) can be fit to the Curie
      Weiss equation with theta = -370, -140, -105, -55, and -120 K, respectively,
      suggesting strong antiferromagnetic coupling. The room temperature effective
      moments, respectively, are 3.71, 4.62, 5.66, 4.54, and 4.91 microB, consistent
      with the above oxidation state assignments. All compounds do not exhibit magnetic
      saturation at 50 kOe, and exhibit frequency-dependent chi'(T) and chi"(T)
      responses characteristic of spin-glass-like behavior. M[Mn(CN)6] order as
      ferrimagnets, with Tc's taken from the peak in the 10 Hz chi'(T) data, of 19, 16,
      27.1, < 1.75, and 4.8 K for M = V, Cr, Mn, Co, and Ni, respectively. The
      structural and magnetic disorder prevents NiII[MnIV(CN)6] from ordering as a
      ferromagnet as anticipated, and structural inhomogeneities allow CoII[MnIV(CN)6]
      and VIII[MnIII(CN)6] to unexpectedly order as ferrimagnets. Also,
      MnIII[MnIII(CN)6] behaves as a reentrant spin glass showing two transitions at 20
      and 27.1 K, and similar behavior is evident for CrIII[MnIII(CN)6]. Hysteresis
      with coercive fields of 340, 130, 8, 9, and 220 Oe and remanent magnetizations of
      40, 80, 1500, 4, and 250 emuOe/mol are observed for M = V, Cr, Mn, Co, and Ni,
      respectively.

PMID- 12526505
TI  - First light-emitting neutral molecular rectangles.

PMID- 12526507
TI  - Structurally reinforced tetraazamacrocyclic complexes.
AB  - The reaction between alkyl or aryl aldehydes and macrocyclic ligands with pendant
      amine groups produced imidazolidine-containing bi- or tricyclic ligands. The
      copper complexes of three of these ligands were structurally characterized:
      [CuL3Cl].3H2O (triclinic, P1, a = 10.041(2) A, b = 10.172(1) A, c = 11.202(1) A,
      alpha = 92.07(1) degrees, beta = 96.76(2) degrees, gamma = 92.99(1) degrees, Z =
      2), [Cu(H2L4)Cl]Cl.2H2O (monoclinic, P2(1)/n, a = 15.159(5) A, b = 10.645(1) A, c
      = 19.094(6) A, beta = 93.78(1) degrees, Z = 4), [CuL5].2H2O.NaNO3 (monoclinic,
      P2(1)/n, a = 10.649(8) A, b = 7.261(2) A, c = 15.25(1) A, beta = 94.77(4)
      degrees, Z = 2). The conformational rigidity and stereochemical activity of these
      macrocycles and their complexes are discussed in comparison with close analogues.

PMID- 12526506
TI  - Aquacobalamin (vitamin B12a) does not bind NO in aqueous solution. Nitrite
      impurities account for observed reaction.

PMID- 12526508
TI  - New rubidium zinc hydrogen phosphate, Rb2Zn2(HPO4)3: synthesis, crystal
      structure, and 31P single-crystal NMR.
AB  - A new rubidium zinc hydrogen phosphate, Rb2Zn2(HPO4)3, is prepared by an unusual
      method utilizing long nucleation times. This material is crystallized from a gel
      with an initial composition of 1.0 ZnO/0.94 P2O5/0.96 Rb2O/0.04 Li2O/41 H2O,
      while the phosphate concentration equals 1.6 M and pH = 3.5. The gel is placed in
      a sealed Pyrex flask at 52 degrees C, and after 4.5 months crystallization of
      Rb2Zn2(HPO4)3 is noticed. This new crystalline compound has a three-dimensional
      framework structure built from spiral chains of alternating PO4 and ZnO4
      tetrahedra connected pairwise and assembled by other PO4 tetrahedra, rubidium
      ions, and hydrogen bonds. The two rubidium ions, Rb(1) and Rb(2), have an
      exceptionally low number of oxygen contacts in the first coordination sphere,
      five and seven, respectively. Crystal data: monoclinic, P2(1)/c (no. 14), a =
      12.5880(4), b = 12.7170(8), c = 7.5827(8) A, beta = 96.100(1) degrees, Z = 4. A
      single-crystal 31P NMR investigation of Rb2Zn2(HPO4)3 was performed employing a
      two-axis goniometer probe and reveals the presence of three chemically and six
      magnetically nonequivalent phosphorus sites, in accordance with the crystal
      structure. 31P chemical shielding anisotropies and isotropic chemical shifts (
      3.3(3), -2.6(3), and 2.0(3) ppm) have been determined for the three phosphorus
      sites.

PMID- 12526509
TI  - Calix[4]arenes as selective extracting agents. An NMR dynamic and conformational
      investigation of the lanthanide(III) and thorium(IV) complexes.
AB  - The lanthanide and Th4+ complexes with calix[4]arene ligands substituted either
      on the narrow or at the wide rim by four coordinating groups behave totally
      differently as shown by an NMR investigation of the dia- and paramagnetic
      complexes. Solutions of complexes were prepared by reacting anhydrous metal
      perchlorate salts with the ligands in dry acetonitrile (CAUTION). Relaxation time
      T1 titrations of acetonitrile solutions of Gd3+ by calixarenes indicate that
      ligands subsituted on the narrow rim form stable 1:1 complexes whether they
      feature four amide groups (1) or four phosphine oxide functions. In contrast, a
      ligand substituted by four (carbamoylmethyl)-diphenylphosphine oxide moieties on
      the wide rim (3) and its derivatives from polymeric species even at a 1:1
      ligand/metal concentration ratio. Nuclear magnetic relaxation dispersion (NMRD)
      curves (relaxation rates 1/T1 vs magnetic field strength) of Gd3+, Gd3+.1 and
      Gd3+.3 perchlorates in acetonitrile are analyzed by an extended version of the
      Solomon-Bloembergen-Morgan equations. A comparison of the calculated rotational
      correlation times tau r shows that ligand 3 forms oligomeric Gd3+ species. The
      chelates of ligand 1 are axially symmetric (C4 symmetry), and the paramagnetic
      shifts induced by the Yb3+ ion are accounted for quantitatively. The addition of
      water or of nitrate ions does not modify the geometry of the complex. The metal
      chelates of 3 and its derivatives adopt a C2 symmetry, and the paramagnetic
      shifts are interpreted on a semiquantitative basis only. Water and NO3- ions
      completely labilize the complexes of the heavy lanthanides. The very high
      selectivity of ligand 3 through the lanthanide series stems from a complex
      interplay of factors.

PMID- 12526510
TI  - Preparation, X-ray crystal structure determination, lattice potential energy, and
      energetics of formation of the salt S4(AsF6)2.AsF3 containing the lattice
      stabilized tetrasulfur [2+] cation. Implications for the understanding of the
      stability of M(4)2+ and M2+ (M = S, Se, and Te) crystalline salts.
AB  - S4(AsF6)2.AsF3 was prepared by the reaction of sulfur with arsenic pentafluroide
      in liquid AsF3 (quantitatively) and in anhydrous HF in the presence of trace
      amounts of bromine. A single-crystal X-ray structure of the compound has been
      determined: monoclinic, space group P2(1)/c, Z = 4, a = 7.886(1) A, b = 9.261(2)
      A, c = 19.191(3) A, beta = 92.82(1) degrees, V = 1399.9(4) A3, T = 293 K, R1 =
      0.052 for 1563 reflections (I > 2 sigma (I) 1580 total and 235 parameters). We
      report a term-by-term calculation of the lattice potential energy of this salt
      and also use our generalized equation, which estimates lattice energies to assist
      in probing the homopolyatomic cation thermochemistry in the solid and the gaseous
      states. We find S4(AsF6)2.AsF3 to be more stable (delta fH degree
      [S4(AsF6)2.AsF3,c] approximately -4050 +/- 105 kJ/mol) than either the unsolvated
      S4(AsF6)2 (delta fH degree [S4(AsF6)2,c] approximately -3104 +/- 117 kJ/mol) by
      144 kJ/mol or two moles of S2AsF6 (c) and AsF3 (1) by 362 kJ/mol. The greater
      stability of the S(4)2+ salt arises because of the greater lattice potential
      energy of the 1:2 solvated salt (1734 kJ/mol) relative to twice that of the 1:1
      salt (2 x 541 = 1082 kJ/mol). The relative lattice stabilization enthalpies of
      M(4)2+ ions relative to two M2+ ions (i.e., in M4(AsF6)2 (c) with respect to two
      M2AsF6 (c) (M = S, Se, and Te)) are found to be 218, 289, and 365 kJ/mol,
      respectively. Evaluation of the thermodynamic data implies that appropriate
      presently available anions are unlikely to stabilize M2+ in the solid phase. A
      revised value for delta fH degree [Se4(AsF6)2,c] = -3182 +/- 106 kJ/mol is
      proposed based on estimates of the lattice energy of Se4(AsF6)2 (c) and a
      previously calculated gasphase dimerization energy of 2Se2+ to Se(4)2+.

PMID- 12526511
TI  - Synthesis, X-ray structure, single-crystal EPR and 1H NMR studies of a distorted
      square planar Cu(salEen)2(ClO4)2 complex in a novel bilayered architecture:
      salEen = N,N-diethylethylenesalicylidenamine.
AB  - Single-crystal X-ray structure and spectroscopic characterizations of
      Cu(salEen)2(ClO4)2, are reported; salEen is a Schiff base condensation product of
      equimolar amounts of salicylaldehyde and N,N-diethylethylenediamine. The complex
      crystallizes in a triclinic space group P1 with a = 12.055(4) A, b = 10.652(3) A,
      c = 12.701(3) A, alpha = 90.54(2) degrees, beta = 94.39(2) degrees, gamma =
      91.35(3) degrees, and Z = 2. The coordination geometry around Cu(II) ion is
      tetrahedrally distorted square planar with salEen coordinating as a neutral
      bidentate ligand through N and O donor atoms (average Cu-N and Cu-O distances are
      2.004 and 1.880 A, respectively). The counterion ClO4- makes H-bonding contacts
      with the neighboring cation moieties and forms a one-dimensional layered
      arrangement of the molecules. The pendent, N,N-diethylethylenediamine groups of
      salEen (from the centrosymmetrically related molecules) in adjacent layers
      interpenetrate, forming novel bilayered architectures, which are further held
      together by pi-pi stacking interactions. EPR studies on single crystals, in three
      mutually orthogonal planes, yield a rhombic g tensor (gx = 2.041(1), gy =
      2.073(1), and gz = 2.220(1)) consistent with the distorted square planar geometry
      of the CuN2O2 moiety. The peak-to-peak line width of the EPR signal exhibits a |3
      cos2 theta - 1|4/3 variation, attributable to one-dimensional magnetic exchange
      behavior of the complex. The analysis suggests that both the dipole-dipole and
      exchange interactions contribute to the line width. Interestingly, the complex is
      amenable for both EPR and NMR studies at ambient temperatures. The proton NMR
      signals are narrow in CD3CN solutions and the HOMO correlation spectroscopy
      (COSY) studies reveal the 1H connectivities. Nuclear spin lattice relaxation time
      (T1) measurements, using inversion recovery method, indicate that T1 values for
      all the protons are remarkably long compared to those of other mononuclear Cu(II)
      complexes.

PMID- 12526512
TI  - Solvothermal route to tin monoselenide bulk single crystal with different
      morphologies.
AB  - Orthorhombic SnSe bulk single crystals with different morphologies were
      conveniently grown through solvothermal process at low temperature (180 degrees
      C). X-ray diffraction (XRD) patterns, scanning electronic microscope (SEM)
      images, electronic diffraction (ED), and X-ray photoelectron spectra (XPS) were
      used to characterize the products. In the solvothermal process, the solvent plays
      an important role in the growth of the single crystal. The morphology of the
      crystal is influenced not only by the kind of solvent but also by the
      concentration of the reactants in solvent. Single crystals with rodlike or
      platelike morphology can be conveniently obtained under controlled concentration
      of reactants in solvent.

PMID- 12526513
TI  - Bond valence sums in coordination chemistry. Calculation of the oxidation state
      of chromium in complexes containing only Cr-O bonds and a redetermination of the
      crystal structure of potassium tetra(peroxo)chromate(V).
AB  - A simple method for calculating the oxidation state of Cr in complexes containing
      only Cr-O bonds is presented. A total of 242 CrOn fragments with n = 3-6 were
      retrieved from the Cambridge Structural Database (CSD) and, together with the
      data for K3CrO8, were analyzed using the bond valence sum method. New R0 values
      for Cr(II) of 1.739(21) A, Cr(III) of 1.708(7) A, Cr(V) of 1.762(14) A, and
      Cr(VI) of 1.793(7) A were derived. An average R0 value of 1.724 A for Cr-O
      reproduces the oxidation state of 96 of the 110 Cr(II), Cr(III), and Cr(IV) CrOn
      complexes (n = 3-6) and that of K3CrO8 within 0.30 valence units. The crystal
      structure of K3CrO8 was redetermined at 173 K to provide accurate data for a Cr
      complex with both high oxidation state and coordination number. Potassium
      tetraperoxochromate(V), K3CrO8, is tetragonal, Space group I42m, a = b =
      6.6940(3) A, c = 7.7536(5) A, Z = 2. The difficulties with fitting the observed
      valence for Cr(V) and Cr(VI) complexes with coordination numbers 4 and 5 are
      discussed. The use of bond valence sums in gaining chemical insight into Cr
      complexes with noninnocent ligands and in establishing oxidation states in Cr
      clusters is presented. An analysis of the Cr-O bond distances used in the
      calculations shows a large range of values that can be understood in terms of the
      bond valence sum calculation.

PMID- 12526514
TI  - Coordination solids derived from Cp*M(CN)3- (M = Rh, Ir).
AB  - Solutions of Rh2(OAc)4 and Et4N[Cp*Ir(CN)3] react to afford crystals of the one
      dimensional coordination solid [Et4N[Cp*Ir(CN)3][Rh2(OAc)4]]. This reaction is
      reversed by coordinating solvents such as MeCN. The structure of the polymer
      consists of helical anionic chains containing Rh2(OAc)4 units linked via two of
      the three CN ligands of Cp*Ir(CN)3-. Use of the more Lewis acidic Rh2(O2CCF3)4 in
      place of Rh2(OAc)4 gave purple [(Et4N)2[Cp*Ir(CN)3]2[Rh2(O2CCF3)4]3], whose
      insolubility is attributed to stronger Rh-NC bonds as well as the presence of
      cross-linking. The species [[Cp*Rh(CN)3][Ni(en)n](PF6)] (n = 2, 3) crystallized
      from an aqueous solution of Et4N[Cp*Rh(CN)3] and [Ni(en)3](PF6)2;
      [[Cp*Rh(CN)3][Ni(en)2](PF6)] consists of helical chains based on cis-Ni(en)(2)2+
      units. Aqueous solutions of Et4N[Cp*Ir(CN)3] and AgNO3 afforded the colorless
      solid Ag-[Cp*Ir(CN)3]. Recrystallization of this polymer from pyridine gave the
      hemipyridine adduct [Ag[Ag(py)][Cp*Ir(CN)3]2]. The 13C cross-polarization magic
      angle spinning NMR spectrum of the pyridine derivative reveals two distinct Cp*
      groups, while in the pyridine-free precursor, the Cp*'s appear equivalent. The
      solid-state structure of [Ag[Ag(py)][Cp*Ir(CN)3]2] reveals a three-dimensional
      coordination polymer consisting of chains of Cp*Ir(CN)3- units linked to
      alternating Ag+ and Ag(py)+ units. The network structure arises by the linking of
      these helices through the third cyanide group on each Ir center.

PMID- 12526515
TI  - Observation of a very large internal hyperfine field (62.4 T) in the
      ferromagnetically ordered state of the S = 1 alpha-iron(II)
      octaethyltetraazaporphyrin.
AB  - The origins of the extraordinarily large internal hyperfine field (62.4 T) for
      the three-dimensional (weak) ferromagnetically ordered ground state of alpha
      Fe(OETAP) are discussed semiquantitatively in terms of existing physical theory.
      In particular, the classical Fermi-contact contribution to the internal field is
      found to be highly enhanced by a very large orbital contribution and a
      significant dipolar term of the same sign. A rationale for the unexpected
      ordering of this S = 1 non-Kramers system is also presented.

PMID- 12526516
TI  - Synthesis and structure of isomeric palladium(II)-pyrazole chelate complexes with
      and without an N-H group as hydrogen bond donor.
AB  - Four new ligands containing a pyrazole ring and either a phosphine or thioether
      were prepared and converted to their cis-dichloropalladium(II) complexes. Two of
      the ligands are especially notable for the attachment of a side chain at pyrazole
      carbon, rather than at nitrogen. The new metal complexes include dichloro[3
      (diphenylphosphinomethyl)pyrazole]palladium(II) (1-PdCl2) and dichloro[3
      (methylthiomethyl)pyrazole]palladium(II) (2-PdCl2), which both feature an N-H
      group as a potential proton or hydrogen bond donor. For comparison, isomeric
      complexes lacking an NH group were prepared: dichloro[1
      (diphenylphosphinomethyl)pyrazole]palladium(II) (3-PdCl2) and dichloro[1
      (methylthiomethyl)pyrazole]palladium(II) (4-PdCl2). As determined by X-ray
      crystallography, all four complexes were found to have slightly distorted square
      planar geometry. Complexes 1-PdCl2 and 2-PdCl2, which contain an NH group,
      exhibit both intermolecular and intramolecular hydrogen bonding, whereas isomers
      3-PdCl2 and 4-PdCl2 do not. Single-crystal X-ray structure determinations on the
      following compounds are reported: 1-PdCl2, space group P1, a = 8.4488(9) A, b =
      8.9175(13) A, c = 12.731(2) A, Z = 2, V = 871.8(2) A3; 2-PdCl2, space group Pbca,
      a = 10.8827(10) A, b = 11.7721(7) A, c = 14.874(2) A, Z = 8, V = 1905.6 A3; 3
      PdCl2, space group P2(1)/c, a = 20.520(2) A, b = 12.549(2) A, c = 13.9784(13) A,
      Z = 8, V = 3401.1(6) A3; 4-PdCl2, space group Pbca, a = 10.6545(10) A, b =
      12.0205(11) A, c = 14.6474(14) A, Z = 8, V = 1875.9(3) A3.

PMID- 12526517
TI  - Crystal structures and magnetic properties of metal complexes bearing four
      nitronyl nitroxide moieties in the same coordination sphere.
AB  - Mononuclear transition metal complexes of the type [M(2,6-NITpy)2](ClO4)2 x
      solvent (2,6-NITpy = 2,6-bis-(3'-oxide-1'-oxyl-4',4',5',5'-tetramethylimidazolin
      2'-yl)pyridine; M = Ni (1), Co (2), Zn (3), Mn (4), Cu (5)) have been synthesized
      and characterized by single-crystal X-ray diffraction studies. Crystal data: 1,
      monoclinic, P2(1)/c, Z = 4, a = 20.946(2) A, b = 12.0633(2) A, c = 21.173(2) A,
      beta = 113.55(1) degrees; 2, monoclinic, P2(1)/c, Z = 4, a = 20.902(2) A, b =
      12.0981(8) A, c = 21.215(2) A, beta = 113.130(9) degrees; 3, triclinic, P1, Z =
      2, a = 11.410(1) A, b = 12.932(1) A, c = 21.609(2) A, alpha = 96.040(2) degrees,
      beta = 102.24(1) degrees, gamma = 114.98(1); 4, monoclinic, P2(1)/n, Z = 4, a =
      11.5473(8) A, b = 19.212(1) A, c = 25.236(2) A, beta = 98.772(9) degrees; 5,
      triclinic, P1, Z = 2, a = 12.1604(9) A, b = 12.6961(9) A, c = 18.103(2) A, alpha
      = 84.191(8) degrees, beta = 73.392(8) degrees, gamma = 66.072(8). The two 2,6
      NITpy biradicals behave as terdentate ligands and bind almost perpendicular to
      each other in meridional positions. In compounds 1-4, the pyridine rings are
      axially ligated and four different nitronyl nitroxide radicals bind to the metal
      center through their O(nitroxyl) atoms, forming the equatorial plane of a
      distorted octahedron. On the contrary, in the copper(II) complex (5), the two
      N(pyridyl) atoms are found in equatorial positions. Only two nitroxide groups are
      then bound to the copper(II) ion in the equatorial plane, the other two being
      axially ligated. The two axially bound nitronyl nitroxide radicals couple
      ferromagnetically to the copper center (JCu-rad(ax) = + 10 K), whereas a strong
      antiferromagnetic coupling between this metal ion and the equatorial nitroxide
      groups (JCu-rad(eq) = -460 K) is observed. The other complexes exhibit strong
      antiferromagnetic metal-radical interactions: JNi-rad = -240 K, for 1; JMn-rad = 
      120 K, for 4. Interestingly, the study of the diamagnetic zinc(II) compound (3)
      reveals a moderate intramolecular antiferromagnetic interaction between radicals
      coordinated to the same metal center (Jrad-rad = -27.7 K). This interaction is
      transmitted through space and is also present in the other complexes: Jrad-rad = 
      14 K, for 1; Jrad-rad = -10 K, for 4; Jrad-rad = -20.5 K, for 5.
      Antiferromagnetic intermolecular interactions are also present in all the
      complexes herein studied.

PMID- 12526518
TI  - Synthesis and dehydrative condensation of square-planar mono- and dinuclear
      hydroxopalladium complexes with the hydrotris(3,5-diisopropylpyrazolyl)borato
      ligand (TpiPr2), TpiPr2(Py)Pd-OH, and (mu-OH)2[PdTpiPr2(H2O)]2.
AB  - Mono- and dinuclear hydroxopalladium complexes (kappa 2-TpiPr2,X)(py)Pd-OH (1; X
      = H, Br) and (mu-OH)2[Pd(kappa 2-TpiPr2)(H2O)]2 (2) are prepared by base
      hydrolysis of the corresponding chloride complexes (kappa 2-TpiPr2,X)(py)Pd-Cl
      (3) and (mu-Cl)2[Pd(kappa 3-TpiPr2)]2 (4), respectively. Functionalization of the
      OH part in 1 is effected via dehydrative condensation with protic substrates (H
      A) to give a series of substituted products, (kappa 2-TpiPr)(py)Pd-A (5), and
      treatment of the dinuclear complex 2 with excess acetic acid affords the
      mononuclear diacetato complex 6, (kappa 2-TpiPr2-H)Pd(OAc)2(HOAc). Complexes 1-4
      and 6 have been characterized crystallographically, and it is revealed that
      complexes 2 and 6 involve cyclic hydrogen-bonding interaction among the nitrogen
      atom of the pendent noncoordinated pyrazolyl group, the hydrogen atom in the
      protic part of the ligand (OH, AcOH), and, in the case of 2, an external water
      molecule.

PMID- 12526519
TI  - Paraoxon and parathion hydrolysis by aqueous molybdenocene dichloride (Cp2MoCl2):
      first reported pesticide hydrolysis by an organometallic complex.
AB  - We report the first case of an organometallic complex that effectively hydrolyzes
      the organophosphate pesticides parathion and paraoxon. The complex is the water
      soluble compound bis(eta 5-cyclopentadienyl)molybdenum(IV) dichloride (1), which
      hydrolyzes parathion to produce ethanol and deethyl parathion in a biphasic
      reaction in D2O. Rate accelerations were 130 and 10(5) at pH 7 and 3,
      respectively. Paraoxon is readily hydrolyzed by 1 to yield p-nitrophenol and
      diethyl phosphate with rate accelerations of 2300 and 27 at pH 7 and 3,
      respectively. Kinetic data for paraoxon hydrolysis by 1 are consistent with a
      process that involves intermolecular (delta S++ = -49 +/- 10 eu) hydroxide attack
      on the phosphate triester in which the aquated 1 serves as a coordinated Lewis
      acid that activates the organophosphate. Interestingly parathion hydrolysis by 1
      occurs via nucleophilic attack at the alpha-carbon of the phosphorothioate
      pesticide that involves C-O bond cleavage. These parathion results represent one
      of the few cases of this type of unusual hydrolytic chemistry and the first case
      of an organometallic complex that accelerates organophosphate pesticide
      hydrolysis.

PMID- 12526520
TI  - Three new polynuclear copper(II) complexes with the symmetric [Cu(mu1,1-N3)2Cu]2+
      core and pyridine derivatives: syntheses, structure, and magnetic behavior.
AB  - Three new polynuclear copper(II) complexes, derived from the end-on azido
      bridging ligand and pyridine derivatives, have been synthesized, and their
      crystal structures have been determined by X-ray diffraction methods; they are
      the dinuclear compounds [Cu2(mu 1,1-N3)2(4-Etpy)4(mu-NO3)2] (1), and [Cu2(mu 1,1
      N3)2(3-ampy)4(mu-NO3)2]. C2H5OH (2), and the trinuclear [Cu3(mu 1,1
      N3)4(N3)2(Meinic)2(DMF)2] (3). 4-Etpy is 4-ethylpyridine, 3-ampy is 3
      aminopyridine, and Meinic is methylisonicotinate. Compound 1, C28H36Cu2N12O6,
      crystallized in the monoclinic system, space group P2(1)/n, with a = 12.355(9) A,
      b = 12.474(4) A, c = 12.854(6) A, beta = 117.68(4) degrees, and Z = 2. Compound
      2, C22H30Cu2N16O7, crystallized in the triclinic system, space group P1, with a =
      9.695(2) A, b = 10.895(2) A, c = 7.909(2) A, alpha = 96.81(3) degrees, beta =
      96.40(3) degrees, gamma = 96.56(3) degrees and Z = 1. Compound 3, C20H28
      Cu3N22O6, crystallized in the monoclinic system, space group P2(1)/n, with a =
      7.755(2) A, b = 14.680(5) A, c = 15.810(5) A, beta = 102.81(2) degrees, and Z =
      2. 1-3 have the symmetric [Cu(mu 1,1-N3)2Cu]2+ core and structural parameters
      outside the previously reported range. Magnetic susceptibility data, measured
      from 2 to 300 K, show strong ferromagnetic coupling for the dinuclear end-on
      compounds 1 and 2 and bulk moderate ferromagnetic coupling for the trinuclear
      compound 3. These data were fitted to the appropriate equations derived from the
      Hamiltonian H = -JS1S2 for 1 and 2 and from the Hamiltonian H = -J1(SA1SB +
      SA2SB) - J2SA1.SA2 for 3, giving the parameters J = 230.1(1) cm-1, g = 2.17(0.01)
      for 1, J = 223.2(2) cm-1, g = 2.16(0.01) for 2, and J1 = 47.3(2) cm-1, J2 = 
      22.5(1) cm-1, gA = 2.26(0.02), gB = 2.07(0.03) for 3. The magnetic susceptibility
      data can be correlated with the structural parameters.

PMID- 12526521
TI  - A trigonal planar mu 3-fluorido coinage metal complex from a dicationic
      (diphosphinomethane)copper(I) dimer: syntheses, structures, and bonding.
AB  - The triflate and hexafluorophosphate salts of [Cu2(mu-dtbpm)2]2+ (1(2+)) [dtbpm =
      bis(di-tert-butylphosphino)methane, tBu2PCH2PtBu2] and of [Cu3(mu 3-F)(mu
      dtbpm)3]2+ (2(2+)) were synthesized and characterized. Coordination of solvent or
      counterions to 1(2+) is observed neither in solution nor in the solid state. The
      two copper(I) centers in 1(2+) indicate weak d10-d10 closed-shell interactions.
      1(2+) reacts slowly with PF6- anions in acetone or KF in CH2Cl2 to yield the mu 3
      fluorido complex 2(2+) with idealized D3 symmetry, containing a trigonal planar
      Cu3F core, as shown by single-crystal X-ray diffraction. Distinct structural
      differences are observed compared to monocationic bicapped, trinuclear copper(I)
      dppm halide complexes [dppm = bis(diphenylphosphino)methane, Ph2PCH2PPh2]. The
      average Cu-Cu, Cu-F, and Cu-P distances and the P-Cu-P' angle in 2(2+) are 3.85,
      2.22, and 2.28 A and 144.3 degrees, respectively. The P2Cu units are twisted out
      of the Cu3F plane by an average angle of 18.4 degrees. DFT calculations
      (BPW91/LANL2DZ) for the model [Cu3(mu 3-F)(mu-dhpm)3]2+ (dhpm =
      diphosphinomethane, H2PCH2PH2) are used to explain the formation, structure, and
      bonding pattern of 2(2+).

PMID- 12526522
TI  - Crystal and molecular structure of an eight-coodinate N
      methyltetraphenylporphyrin complex: diacetato(N-methyl-meso
      tetraphenylporphyrinato)thallium(III).
AB  - The crystal structure of diacetato(N-methyl-meso
      tetraphenylporphyrinato)thallium(III), Tl(N-Me-tpp)(OAc)2 (1), was established,
      and the coordination sphere around the Tl3+ ion is described as an eight
      coordinate square-based antiprism in which two cis chelating bidentate OAc-
      groups occupy two apical sites. The plane of the three pyrrole nitrogen atoms
      (i.e., N(1), N(3), N(4)) strongly bonded to Tl3+ is adopted as a reference plane
      3N. The pyrrole N(2) ring bearing the methyl group (i.e., C(45)H3) is the most
      deviated one from the 3N plane, making a dihedral angle of 21.4 degrees, whereas
      smaller angles of 9.1 degrees, 7.1 degrees, and 0.9 degree occur with pyrroles
      N(1), N(3), and N(4), respectively. Because of its larger size, the thallium(III)
      ion Tl3+ is considerably out of the 3N plane; its displacement of 1.17 A is in
      the same direction as that of the two apical OAc- ligands. The intermolecular
      acetate exchange process for 1 in THF-d8 solvent is examined through 1H NMR
      temperature-dependent measurements. In the slow-exchange region, the methyl and
      carbonyl carbons of the OAc- groups in 1 are separately located at delta 18.6
      [3J(Tl-13C) = 405 Hz] and 170.8 [2J(Tl-13C) = 334 Hz] at -80 degrees C,
      respectively.

PMID- 12526523
TI  - Synthesis of arene-soluble mixed-metal Zr/Ce, Zr/Y, and related
      [[Zr2(OiPr)9]LnX2]n complexes using the dizirconium nonaisopropoxide ligand.
AB  - The utility of polydentate monoanionic [Zr2(OiPr)9]- in generating arene-soluble,
      unsolvated, mixed-metal Zr/Ce and Zr/Y complexes is described. The synthesis of
      other mixed-metal zirconium lanthanide complexes was also studied to explore the
      relationship of metal size to structure. Lanthanide trihalides react in THF with
      KZr2(OiPr)9 to form unsolvated dimers, [[Zr2(OiPr)9]LnCl2]2, with the larger
      metals, Ln = Ce (1), Ho (2), Y (3), and unsolvated monomers, [Zr2(OiPr)9]LnCl2,
      with the smaller elements, Ln = Er (4), Yb (5). The synthesis of a monomeric
      iodide analogue, [Zr2(OiPr)9]TmI2, 6, by reduction of Zr2(OiPr)8(iPrOH)2 with
      TmI2(DME)3 is also reported. In all of these complexes, the [Zr2(OiPr)9]- subunit
      is tetradentate. 1-6 are compared with related cyclopentadienyl halide complexes
      to evaluate the special features of the dizirconium nonaisopropoxide ligand
      versus cyclopentadienide.

PMID- 12526524
TI  - Eu(III) macrocyclic complexes promote cleavage of and bind to models for the 5'
      cap of mRNA. Effect of pendent group and a second metal ion.
AB  - The interaction of three Eu(III) macrocyclic complexes Eu(THED)3+, Eu(ATHC)3+,
      and Eu(ATHC)3+, and Eu(S-THP)3+ with two 5'-cap model compounds, GpppG and
      m7GpppG is studied (THED = 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,-10
      tetraazacyclododecane, ATHC = 1-(carbamoylmethyl)-4,7,10-tris(2-hydroxyethyl)
      1,4,7,10- tetraazacyclododecane, S-THP = 1S,4S,7S,10S-tetrakis(2-hydroxypropyl)
      1,4,7,10-tetraazacyclododecane). Laser-induced excitation luminescence
      spectroscopy is used to study the binding of Eu(S-THP)3+ to GpppG (K = 5.9 x
      10(4) M-1) and to characterize the Eu(S-THP)-GpppG complex. Both Eu(THED)3+ and
      Eu(S-THP)3+ bind to m7GpppG as monitored by use of fluorescence spectroscopy with
      binding constants of 5.9 x 10(3) and 4.4 x 10(4) M-1, respectively. The kinetics
      of cleavage of GpppG by two macrocyclic complexes is studied. Cleavage of GpppG
      by Eu(THED)3+ is accelerated by 15-fold in the presence of an equivalent of
      Zn(NO3)2 at pH 7.3, 37 degrees C, suggesting that two metal ions accelerate the
      cap cleavage reaction. Eu(ATHC)3+ promotes cleavage of GpppG with a pseudo-first
      order rate constant of 2.6 x 10(-5) s-1 at pH 7.3, 37 degrees C, and 0.30 mM
      complex.

PMID- 12526525
TI  - Characterization of divalent metal metavanadates by 51V magic-angle spinning NMR
      spectroscopy of the central and satellite transitions.
AB  - 51V quadrupole coupling and chemical shielding tensors have been determined from
      51V magic-angle spinning (MAS) NMR spectra at a magnetic field of 14.1 T for nine
      divalent metal metavanadates: Mg(VO3)2, Ca(VO3)2, Ca(VO3)(2).4H2O, alpha
      Sr(VO3)2, Zn(VO3)2, alpha- and beta-Cd(VO3)2. The manifold of spinning sidebands
      (ssbs) from the central and satellite transitions, observed in the 15V MAS NMR
      spectra, have been analyzed using least-squares fitting and numerical error
      analysis. This has led to a precise determination of the eight NMR parameters
      characterizing the magnitudes and relative orientations of the quadrupole
      coupling and chemical shielding tensors. The optimized data show strong
      similarities between the NMR parameters for the isostructural groups of divalent
      metal metavanadates. This demonstrates that different types of metavanadates can
      easily be distinguished by their anisotropic NMR parameters. The brannerite type
      of divalent metal metavanadates exhibits very strong 51V quadrupole couplings
      (i.e., CQ = 6.46-7.50 MHz), which reflect the highly distorted octahedral
      environments for the V5+ ion in these phases. Linear correlations between the
      principal tensor elements for the 51V quadrupole coupling tensors and electric
      field gradient tensor elements, estimated from point-monopole calculations, are
      reported for the divalent metal metavanadates. These correlations are used in the
      assignment of the NMR parameters for the different crystallographic 51V sites of
      Ca(VO3)(2).4H2O, Pb(VO3)2, and Ba(VO3)2. For alpha-Sr(VO3)2, with an unknown
      crystal structure, the 51V NMR data strongly suggest that this metavanadate is
      isostructural with Ba(VO3)2, for which the crystal structure has been reported.
      Finally, the chemical shielding parameters for orthovanadates and mono- and
      divalent metal metavanadates are compared.

PMID- 12526526
TI  - Structural studies of silver(I) coordination polymers with aryl iodide derived
      ligands.
AB  - This paper reports novel silver polymers, built with iodine--silver interactions,
      with interesting structural motifs. Four silver(I) coordination polymers of the
      aryl iodide derived ligands, triiodobenzoic acid (HL1), tris(4-iodophenyl)amine
      (L2), and 5,7-diiodo-8-hydroxyquinoline (HL3), have been synthesized and
      characterized by X-ray crystallography. Treatment of Ag(CH3COO) with HL1 yielded
      [Ag(L1)] (1), whose structural analysis revealed 2D layers of ladders connected
      through weak Ag...I interaction. Reactions of AgClO4 and L2 in benzene and
      nitrobenzene afforded, respectively, two different products,
      [Ag(L2)(H2O)]ClO4.C6H6(2) and [Ag(L2)(ClO4)](3). While the structure of 2 could
      be described as a 2D layer of square and octagons perpendicular to [100], complex
      3 is formed by 2D layers of the same topology of 2 (8(2).4), alternating as ABAB.
      In contrast, complex 4, [Ag2(H2L3)(CF3SO3)3], obtained by reaction of Ag(CF3SO3)
      and HL3, was found to consist of a 2D layer based on columnar arrays AgH2L3
      Ag(triflate). The solid-state FT-IR and 109Ag NMR spectra of theses complexes are
      discussed on the basis of their crystal structures.

PMID- 12526527
TI  - The lowest-energy ligand to metal charge-transfer absorption band of trans
      [OsO2(malonate)2]2-.
AB  - The resolved structure of the lowest-energy oxo to osmium charge-transfer
      absorption band of trans-[OsO2(malonate)2]2- is analyzed on the basis of the
      exact molecular Ci symmetry determined from the structure of a crystal used for
      spectroscopy. The multiple progressions observed in the polarized spectra are
      rationalized in terms of the deviations from idealized D4h point group symmetry
      and compared to the spectra observed for complexes with D2h symmetry such as
      trans-[OsO2(oxalate)2]2- that show only a single dominant progression for this
      transition.

PMID- 12526528
TI  - Polyamine macrocycles incorporating a phenolic function: their synthesis,
      basicity, and coordination behavior toward metal cations. Crystal structure of a
      binuclear nickel complex.
AB  - The synthesis and characterization of two new polyazamacrocycles, 1,4,7,10
      tetraaza[12](2,6)phenolphane (L1) and 1,4,7,10,13-pentaaza[15](2,6)phenolphane
      (L2), are reported. Both ligands incorporate the 2,6-phenolic unit within the
      cyclic framework. The basicity behavior and the ligational properties of L1 and
      L2 toward Ni(II), Zn(II), and Cu(II) were determined by means of potentiometric
      measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm-3). UV spectra
      were used to understand the role of the phenolic function in the stabilization of
      the cations. L1 and L2 behave as pentaprotic bases under the experimental
      conditions used. The UV spectra showed that the deprotonation of the phenolic
      function occurs at low pH values for both ligands, giving rise to the
      simultaneous presence of positive and (one) negative charges on the macrocycle.
      While L1 forms only mononuclear complexes, L2 can also form binuclear species
      with all the metal ions investigated. In the mononuclear species of both ligands,
      one nitrogen atom close to the phenol remains unbound. The UV spectra revealed
      that the phenol, bridging the two metal ions in phenolate form, plays an
      important role in the stabilization of the binuclear complexes of L2. The
      coordination sphere of the two metals is completed by adding a secondary ligand
      such as water molecules or OH-, in any case preferring substrates able to bridge
      the two close metal ions. These results are confirmed by the crystal structure of
      [Ni2(C16H28ON5)(H2O)2Cl2]Cl.H2O.CH3OH (space group P21/a, a = 14.821(5) A, b =
      10.270(4) A, c = 17.663(6) A, beta = 108.87(3) degrees, V = 2544(2) A3, Z = 4, R1
      = 0.0973, wR2 = 0.2136). This structure displays a Ni(II) binuclear complex of L2
      in which the phenolic oxygen and a chlorine ion bridge the two close Ni(II) ions.

PMID- 12526529
TI  - Oxidation of sulfoxides by hydrogen peroxide, catalyzed by
      methyltrioxorhenium(VII).
AB  - Dialkyl and diaryl sulfoxides are oxidized to sulfones by hydrogen peroxide using
      methyltrioxorhenium as the catalyst. The reaction rate is negligible without a
      catalyst. The kinetics study was performed in CH3CN-H2O (4:1 v/v) at 298 K with
      [H+] at 0.1 M, conditions which make the equilibration between MTO and its peroxo
      complexes more rapid than the oxygen-transfer step. The values for the rate
      constant for the oxygen-transfer step lie in the range 0.1-3 L mol-1 s-1. The
      rate constants were significantly smaller than for the oxidation of sulfides to
      sulfoxides. A study of ring-substituted diaryl sulfoxides yielded kinetics
      results that are consistent with nucleophilic attack of the sulfur atom on the
      peroxide oxygen group since rho = -0.65. The results cited refer to the reactions
      of the diperoxo from the catalyst, MeRe(O)(eta 2-O2)2H2O. The monoperoxo complex
      showed no measurable reactivity toward sulfoxides, in contrast with the situation
      for nearly every other substrate. That unusual finding suggests a hydrogen-bonded
      interaction between the substrate and the diperoxorhenium compound which cannot
      exist with the monoperoxo compound.

PMID- 12526530
TI  - Divalent samarium compounds with heavier chalcogenolate (EPh; E = Se, Te)
      ligands.
AB  - Crystalline coordination complexes of Sm(EPh)2 (E = Se, Te) are described. The
      selenolate compound Sm(SePh)2 is unstable in solution, but a divalent selenolate
      can be prepared and isolated when precisely 1 equiv of Zn(SePh)2 is present to
      form heterometallic [(THF)3Sm(mu 2-SePh)3Zn(mu 2-SePh)]n (1). This compound is a
      1D coordination polymer with alternating Sm(II) and Zn(II) ions connected by an
      alternating (1,3) number of bridging selenolate ligands and three THF ligands
      bound to each Sm(II) ion. The tellurolate Sm(TePh)2 forms a stable pyridine
      coordination compound (py)5Sm(TePh)2 (2) that is isostructural with known Eu and
      Yb benzenetellurolates. Both compounds were characterized by conventional
      spectroscopic methods. Polymer 1 was characterized by low-temperature single
      crystal X-ray diffraction, and the unit cell of the tellurolate was determined.
      Crystal data (Mo K alpha, 153(5) (K) are as follows. 1: monoclinic space group
      P21, a = 10.666(2) A, b = 16.270(3) A, c = 12.002(3) A, beta = 114.81(2) degrees,
      Z = 2.2: orthorhombic space group Pbca, with a = 13.865(3) A, b = 16.453(5) A, c
      = 31.952(7) A, Z = 8.

PMID- 12526531
TI  - The synthesis and the molecular structure of
      hexakis(carbonyl)hexafluoroantimonato(V)tungsten(II) undecafluorodiantimonate(V),
      [W(CO)6(FSbF5)][Sb2F11].
AB  - The reaction of tungsten hexacarbonyl, W(CO)6, with antimony(V) fluoride, SbF5,
      in the conjugate Bronsted-Lewis superacid HF-SbF5 at 40 degrees C produces
      quantitatively the salt [W(CO)6(FSbF5)][Sb2F11] as the main product. The observed
      2e- oxidation without any loss of CO is unprecedented. The cation
      [W(CO)6(FSbF5)]+ is seven coordinated with a distorted C2v capped trigonal
      prismatic structure. [W(CO)6(FSbF5)][Sb2F11] crystallizes in the monoclinic space
      group P21 (No. 4). a = 8.2051(12) A, b = 16.511(3) A, c = 8.1432(2) A, beta =
      111.5967(6) degrees, V = 1025.8(2) A3, Z = 2. Number of reflections measured =
      9112, unique 4410. Residuals on F, I > 3 sigma (I): R (Rw) = 0.023 (0.023). In
      the [W(CO)6(FSbF5)]+ cation the FSbF5 group is very tightly coordinated to
      tungsten with the bridging fluorine nearly equidistant from W and Sb. The details
      of the molecular structure are compared to those to polymeric [[Mo(CO)4]2(cis-mu
      F2SbF4)3]x[Sb2F11]x reported by us very recently.

PMID- 12526532
TI  - Synthesis and characterization of six-coordinate "3 + 2" mixed-ligand oxorhenium
      complexes with the o-diphenylphosphinophenolato ligand and tridentate coligands
      of different N and S donor atom combinations.
AB  - A series of octahedral six-coordinate oxorhenium(V) mixed ligand complexes
      containing the common [ReO(L)]2+ fragment (L = o-OC6H4P(C6H5)2] have been
      synthesized and characterized. Hence, it was shown that the [ReO(L)]2+ moiety can
      accommodate a variety of tridentate ligands containing a central amine group
      amenable to deprotonation and different combinations of lateral groups, such as
      ethylamine, substituted ethylamine, ethylthiol, and ethylthioether arms. In
      particular, by reaction of equimolar amounts of the pertinent HLn ligands with
      the [(n-C4H9)4N][ReOCl3(L)] precursor in refluxing acetonitrile/methanol or
      dichloromethane/methanol mixtures, the following series of [ReO(Ln)(L)]+/0
      oxorhenium(V) complexes has been generated: ReO[[N(CH2CH2NH2)2][o
      OC6H4P(C6H5)2]]Cl (1); ReO[[C2H5)2NCH2CH2NCH2CH2S][o-OC6H4P5)2]] (2);
      ReO[[(CH2)4NCH2CH2NCH2CH2S][o-OC6H4P(C6H4P(C6H5)2]] (3); and
      ReO[[C2H5SCH2CH2NCH2CH2S][o-OC6H4P(C6H5)2]] (4). The complexes are closed-shell
      18-electron oxorhenium species, which adopt octahedral geometries both in
      solution and in the solid state, as established by conventional physicochemical
      techniques including multinuclear NMR and single-crystal X-ray diffraction
      analyses.

PMID- 12526533
TI  - Structural studies of indium and thallium insertion into the framework of the
      cluster compound Ti2Nb6Cl14O4.
AB  - We have investigated the possibility of altering the electronic configuration of
      the niobium oxochloride cluster compound Ti2Nb6Cl14O4 (I) by doping this material
      with monovalent cations that can fit into cavities present in its cluster
      framework. The doping of I with In+ and Tl+ ions resulted in the formation of
      MxTi2Nb6Cl14-xO4+x (M = In, x = 0.10, 0.20, 0.27; M = Tl, x = 0.10, 0.20) in
      which the M+ ions partially occupy these cavities. The crystal structure analysis
      indicated that the additional charge provided by M+ ions is compensated by
      substitution of chlorine by oxygen, which leads to the cluster electronic
      configuration being intact. Crystal data: In0.272Ti2Nb6Cl13.728O4.272, space
      group C2/c (No. 15), a = 12.679(2) A, b = 14.567(2) A, c = 12.632(3) A, beta =
      95.26(2) degrees, Z = 4; Tl0.196Ti2Nb6Cl13.804O4.196, space group C2/c (no. 15),
      a = 12.732(1) A, b = 14.607(2) A, c = 12.662(2) A, beta = 95.28(1) degrees, Z =
      4.

PMID- 12526534
TI  - Pillared, 3D metal-organic frameworks with rectangular channels. Synthesis and
      characterization of coordination polymers based on tricadmium carboxylates.
AB  - Hydro(solvo)thermal reactions between cadmium(II) perchlorate and 4
      pyridinecarboxaldehyde in the presence of various guest molecules have resulted
      in a series of 3-D coordination polymers based on tricadmium carboxylates
      [Cd6(isonicotinate)10(H2O)2](ClO4)2(EtOH)4(H2O)4, 1, [Cd3(isonicotinate)5
      (EtOH)](ClO4)(EtOH)(4-nitroaniline)0.5, 2, and
      [Cd6(isonicotinate)11](ClO4)(EtOH)2(H2O)2(4-cyanopyridine)0.5, 3. X-ray single
      crystal structure determinations show that they exhibit similar pillared, 3D
      framework structures based on tricadmium carboxylate building blocks. Rectangular
      channels are clearly present in these polymeric networks and are occupied by
      perchlorate anions and disordered guest molecules. Quantitative NMR and X-ray
      powder diffraction studies and thermogravimetric analyses (TGA) reveal that these
      coordination networks are capable of accommodating different guest molecules.
      More significantly, the guest molecules can be readily removed via evacuation to
      result in nanoporous polymeric coordination networks retaining the framework
      structures of the pristine solids. Crystal data for 1: monoclinic space group
      P2(1)/n, a = 19.041(1) A, b = 23.654(1) A, c = 21.568(1) A, beta = 95.440(1)
      degrees, and Z = 4. Crystal data for 2: triclinic space group P1, a = 12.050(1)
      A, b = 12.277(1) A, c = 19.103(1) A, alpha = 91.669(1) degrees, beta = 96.850(1)
      degrees, gamma = 117.945(1) degrees, and Z = 2. Crystal data for 3: monoclinic
      space group P2(1)/n, a = 19.038(1) A, b = 23.834(1) A, c = 21.756(1) A, beta =
      97.580(1) degrees, and Z = 4.

PMID- 12526535
TI  - Cyclotriphosphorus complexes: solid-state structures and dynamic behavior of
      monoadducts with carbonyl fragments.
AB  - Treatment of the cyclo-P3 complexes [(triphos)MP3] [triphos = 1,1,1
      tris(diphenylphosphinomethyl)ethane; M = Co (1), Rh (2)] with stoichiometric
      amounts of [M'(CO)5(thf)]n+ (n = 0, M' = Cr, Mo, W; n = 1, M' = Re) and
      [W(CO)4(PPh3)(thf)] yields the compounds [[(triphos)M](mu,eta 3:1-P3) [M'(CO)5]]
      [M = Co; M' = Cr (3a), Mo (3b), W (3c). M = Rh; M' = W (4)],
      [[(triphos)Co](mu,eta 3:1-P3)[Re(CO5)]]BF4.C7H8 (5) and [[(triphos)Rh](mu,eta 3:1
      P3)[W(CO)4PPh3]].2CH2Cl2 (6). The X-ray structures of 5 and 6 have been
      determined. Crystal data: 5, monoclinic space group P2(1)/n, a = 14.754(2) A, b =
      24.886(4) A, c = 15.182(2) A, beta = 103.38(1) degrees, Z = 4; 6, monoclinic
      space group P2(1)/n, a = 14.872(3) A, b = 27.317(6) A, c = 16.992(4) A, beta =
      111.75(5) degrees, Z = 4. The effects of eta 1 coordination on the MP3 core are
      discussed by comparing the MP3 skeletons in the above structures with those of
      the previously characterized bis and tris end-on adducts of organometallic
      fragments of 1. Variable temperature NMR data for the compounds provide evidence
      for fluxional processes in solution that may be interpreted as [(triphos)M]
      rotation about its C3 axis and [M'(CO)5] or [M'(CO)4PPh3] scrambling over the P3
      cycle. The activation parameters of the fragment scrambling process are
      determined.

PMID- 12526536
TI  - On the nature of the trigonal fields in hexaaquachromium(III) in guanidinium
      aluminum sulfate hexahydrate.
AB  - Zeeman and site selective luminescence and excitation spectra in the region of
      the 2E<--4A2 transition are reported for the hexaaquachromium(III) complex in the
      trigonal ferroelectric guanidinium aluminum sulfate hexahydrate. The two
      prominent transitions are due to the R1 lines of the two sites of C3 and C3v
      point symmetry. The two R1 lines display g parallel = -3.1 and g parallel = -3.2,
      respectively, and show no measurable Zeeman shift or splitting with B
      perpendicular c. This behavior is consistent with the presence of a very large
      trigonal field. A peculiar feature of the present system is the conspicuous
      absence of any prominent R2 line. From the Zeeman data with B perpendicular c and
      a comparison of vibrational sidelines in excitation and luminescence it is
      concluded that the R2 level strongly interacts with vibrational levels.

PMID- 12526537
TI  - Oxidation of ammonia in osmium polypyridyl complexes.
AB  - The oxidations of cis- and trans-[OsIII(tpy)(Cl)2(NH3)](PF6), cis
      [OsII(bpy)2(Cl)(NH3)](PF6), and [OsII(typ)(bpy)(NH3)](PF6)2 have been studied by
      cyclic voltammetry and by controlled-potential electrolysis. In acetonitrile or
      in acidic, aqueous solution, oxidation is metal-based and reversible, but as the
      pH is increased, oxidation and proton loss from coordinated ammonia occurs. cis-
      and trans-[OsIII(tpy)(Cl)2(NH3)](PF6) are oxidized by four electrons to give the
      corresponding OsVI nitrido complexes, [OSVI(typ)(Cl)2(N)]+. Oxidation of
      [Os(typ)(bpy)(NH3)](PF6)2 occurs by six electrons to give
      [Os(tpy)(bpy)(NO)](PF6)3. Oxidation of cis-[OsII(bpy)2(Cl)(NH3)](PF6) at pH 9.0
      gives cis-[OsII(bpy)2(Cl)(NO)](PF6)2 and the mixed-valence form of the mu-N2
      dimer [cis-[Os(bpy)2(Cl)2[mu-N2)](PF6)3. With NH4+ added to the electrolyte, cis
      [OsII(bpy)2(Cl)(N2)](PF6) is a coproduct. The results of pH-dependent cyclic
      voltammetry measurements suggest OsIV as a common intermediate in the oxidation
      of coordinated ammonia. For cis- and trans-[OsIII(tpy)(Cl)2(NH3)]+, OsIV is a
      discernible intermediate. It undergoes further pH-dependent oxidation to
      [OsVI(tpy)(Cl)2(N)]+. For [OsII(tpy)(bpy)(NH3)]2+, oxidation to OsIV is followed
      by hydration at the nitrogen atom and further oxidation to nitrosyl. For cis
      [OsII(bpy)2(Cl)-(NH3)]+, oxidation to OsIV is followed by N-N coupling and
      further oxidation to [cis-[Os(bpy)2(Cl)2(mu-N2)]3+. At pH 9, N-N coupling is
      competitive with capture of OsIV by OH- and further oxidation, yielding cis
      [OsII(bpy)2(Cl)(NO)]2+.

PMID- 12526538
TI  - Synthesis, structural characterization, and theoretical calculations of a new
      copper(I)-octahydrotriborate complex.

PMID- 12526539
TI  - Supramolecular assemblies based on cucurbituril adducts of hydrogen-bonded
      molybdenum and tungsten incomplete cuboidal aqua complexes.

PMID- 12526540
TI  - Ligand control on molecular oxygen activation by rhodium quinone complexes.

PMID- 12526541
TI  - Molecular ladders with multiple interpenetration of the lateral arms into the
      squares of adjacent ladders observed for [M2(4,4'-bpy)3(H2O)2(phba)2]
      (NO3)(2).4H2O (M = Cu2+ or Co2+; 4,4'-bpy = 4,4'-bipyridine; phba = 4
      hydroxybenzoate).

PMID- 12526542
TI  - Three-dimensional oxalate-bridged heterometal supramolecular complex with a large
      helical tunnel of 21.191 x 9.294 A 2.

PMID- 12526543
TI  - 10-vertex closo-boranes as potential pi linkers for electronic materials.

PMID- 12526544
TI  - Direct synthesis of a bis(pyrazolyl)boratocopper(I) complex: synthesis and
      characterization of [H2B(3,5-(CF3)2Pz)2]Cu(PPh3)2 displaying an unusual
      coordination mode for a poly(pyrazolyl)borate ligand.

PMID- 12526545
TI  - Structure and magnetic characteristics of an oxalate-bridged U(IV)-Mn(II) three
      dimensional network.

PMID- 12526546
TI  - Synthesis, characterization, and polymerization activity of [bis(4,4'
      bis(neophyldimethylsilylmethyl)-2,2'-bipyridyl)copper(I)]+CuBr2- and Implications
      for copper(I) catalyst structures in atom transfer radical polymerization.
AB  - A series of 4,4'-disilyl-substituted-2,2'-bipyridine ligands were prepared using
      a metathesis reaction of the dianion of 4,4'-dimethyl-2,2'-bipyridine with
      several trialkylsilyl chlorides: 4,4'bis(tert-butyldimethylsilylmethyl)-2,2'
      bipyridine (dTBDMSbipy), 4,4'-bis(dimethylthexylsilylmethyl)-2,2'-bipyridine
      (dTHEXbipy), and 4,4'-bis(neophyldimethylsilylmethyl)-2-2'-bipyridine (dNEObipy).
      It was observed that the side chain length correlated with the ability of the
      ligand to form hydrocarbon soluble complexes of copper(I) bromide, with dNEObipy
      forming the most soluble and easily crystallized complexes. The atom transfer
      radical polymerization (ATRP) of styrene using dNEObipy as the ligand displayed
      molecular weight control equivalent to other ATRP systems in which solubilizing
      ligands, such as 4,4'-di-5-nonyl-2,2'-bipyridine or 4,4'-di-n-heptyl-2,2'
      bipyridine, were used. The one-to-one complex of dNEObipy with CuBr was prepared
      and its crystal structure was determined. The resulting complex had the ionic
      formulation [(dNEObipy)2Cu]+[CuBr2]- and displayed similar activities in styrene
      ATRP as the standard 2 dNEObipy/CuBr catalyst system. These and other
      polymerization results in addition to NMR experiments suggest that the
      predominant copper(I) species formed in ATRP solutions is the 2-to-1 ligand-to
      copper(I) cation, [(dNEObipy)2Cu]+, with either a dihalocuprate or halide
      counteranion, depending upon the conditions.

PMID- 12526547
TI  - Titanium alkoxide complexes: condensed phase and gas phase comparisons.
AB  - The complex [Ti(2,4-dimethyl-2,4-pentanediolate)2]2 (1) has been synthesized from
      [Ti(OiPr)4] by transesterification with a stoichiometric amount of 2,4-dimethyl
      2,4-pentanediol. We have characterized complex 1 in the solid state by single
      crystal X-ray diffraction and in the gas phase by desorption chemical ionization
      mass spectrometry (DCI-MS). The structural and mass spectrometric data show
      complex 1 to be stable as a dimer in both the solid and gas phases. The retention
      of dimeric nuclearity in the gas phase sets complex 1 apart from other simple
      titanium alkoxide complexes [Ti(OiPr)4] and [Ti(OMe)4]4 that give rise to
      respective families of molecular ions in the DCI-MS experiment. The highest mass
      molecular ions for Ti alkoxide complexes in the gas phase may reveal the highest
      nuclearity that these complexes achieve in condensed phases. According to this
      interpretation the complex [Ti(OiPr)4] is principally dimeric in the gas phase
      and probably also in the pure liquid phase and should be represented by the
      formula [Ti(OiPr)4]2.

PMID- 12526548
TI  - Adduct formation between alkali metal ions and divalent metal salicylaldimine
      complexes having methoxy substituents. A structural investigation.
AB  - Sodium, potassium, and cesium salts (iodides, nitrates, acetates, and
      tetraphenylborates) form 1/1, 1/2 and 2/3 adducts with MLn [M = Co, Ni, Cu, and
      Zn; n = 1-4; H2L1 = N,N'-(3-methoxysalicyliden)ethane-1,2-diamine; H2L2, H2L3,
      and H2L4 are the -propane-1,2-diamine, -o-phenylenediamine, and -propane-1,3
      diamine analogues of H2L1). Metal salicyladimine, alkali metal, and anion all
      exert influence on stoichiometry and reactivity. Sodium ions tend to reside
      within the planes of the salicylaldimine oxygens, as in Na(NO3)(MeOH).NiL4 (1),
      Na(NO3)(MeOH).CuL1 (2; both with unusual seven-coordinated sodium), and
      Na.(NiL4)2I.EtOH.H2O (3; with dodecahedral sodium coordination geometry).
      Potassium and cesium tend to locate between salicylaldimine ligands as in KI.NiL4
      (4) and [Cs(NO3).NiL4]3.MeOH (5; structures with infinite sandwich assemblies),
      CsI.(NiL2)2.H2O (6), CsI3.(NiL4)2 (7; simple sandwich structures), and
      [K(MeCN)]2.(NiL4)3 (8; a triple-decker sandwich structure). Crystal data for 1
      are the following: triclinic, P1, a = 7.3554(6) A, b = 11.2778(10) A, c =
      13.562(2) A, alpha = 96.364(10) degrees, beta = 101.924(9) degrees, gamma =
      96.809(10) degrees, Z = 2. For 2, triclinic, P1, a = 7.2247(7) A, b = 11.0427(6)
      A, c = 13.5610(12) A, alpha = 94.804(5) degrees, beta = 98.669(7) degrees, gamma
      = 99.26(6) Z = 2. For 3, orthorhombic, Pbca, a = 14.4648(19) A, b = 20.968(3) A,
      c = 28.404(3) A, Z = 8. For 4, triclinic, P1, a = 12.4904(17) A, b = 13.9363(13)
      A, c = 14.1060(12) A, alpha = 61.033(7) degrees, beta = 89.567(9) degrees, gamma
      = 71.579(10) degrees, Z = 2. For 5, monoclinic. P2(1)/n, a = 12.5910(2) A, b =
      23.4880(2) A, c = 22.6660(2) A, beta = 99.3500(1) degree, Z = 4. For 6,
      orthorhombic, Pbca, a = 15.752(3) A, b = 23.276(8) A, c = 25.206(6) A, Z = 8. For
      7, triclinic, P1, a = 9.6809(11) A, b = 10.0015(13) A, c = 11.2686(13) A, alpha =
      101.03 degrees, beta = 90.97 degrees, gamma = 100.55 degrees, Z = 2. For 8,
      monoclinic, C2/c, a = 29.573(5) A, b = 18.047(3) A, c = 23.184(3) A, beta =
      122.860(10) degrees, Z = 8.

PMID- 12526549
TI  - Synthesis, spectroscopic characterization, and crystal structure of the
      bimetallic complex [Ni2(mu-CO)(CO)2(mu-NH(PPh2)2)2].
AB  - The dinuclear Ni(0) complex [Ni2(mu-CO)(CO)2(mu-dppa)2] (1; dppa =
      bis(diphenylphosphino)amine) was synthesized by two routes in good yield. Complex
      1 has a triclinic crystal system and P1 space group, with a = 13.009(1) A, b =
      13.063(2) A, c = 14.664(2) A, alpha = 79.91(1) degrees, beta = 79.96(1) degrees,
      gamma = 71.32(1) degrees, and Z = 2. The structure of this compound exhibits two
      mu-coordinated dppa ligands in a cis, cis arrangement. Nickel atoms are at a
      2.5824(7) A distance. Theoretical calculations predict a 0.39 bond order between
      metal atoms. The cyclic voltammograms show two quasi-reversible redox pairs,
      which correspond to the successive oxidation of the metal centers. The dinuclear
      complex described absorbs carbon monoxide, yielding a mixture of nickel carbonyl
      compounds.

PMID- 12526550
TI  - 1H- and 2H-T1 relaxation behavior of the rhodium dihydrogen complex
      [(triphos)Rh(eta 2-H2)H2]+.
AB  - Protonation of the classical trihydride [(triphos)RhH3] (2) at 210 K in either
      THF or CH2Cl2 by either HBF4.OMe2 or CF3SO2OH gives the nonclassical eta 2-H2
      complex [(triphos)Rh(eta 2-H2)H2]+ (1) [triphos = MeC(CH2PPh2)3]. Complex 1 is
      thermally unstable and highly fluxional in solution. In THF above 230 K, 1
      transforms into the solvento dihydride complex [(triphos)Rh(eta 1-THF-d8)H2]+ (5)
      that, at room temperature, quickly converts to the stable dimer trans
      [[(triphos)RhH]2(mu-H)2]2+ (trans-6). In CH2Cl2, 1 is stable up to 240 K. Above
      this temperature, the eta 2-H2 complex begins to convert into a mixture of trans-
      and cis-6, which, in turn, transform into the bridging-chloride dimers trans- and
      cis-[[(triphos)RhH]2(mu-Cl)2]2+ at room temperature. Complex 1 contains a fast
      spinning H2 ligand with a T1min of 38.9 ms in CD2Cl2 (220 K, 400 MHz). An NMR
      analysis of the bis-deuterated isotopomer [(triphos)RhH2D2]+ (1-d2) did not
      provide a J(HD) value. At 190 K, the perdeuterated isotopomers [(triphos)RhD3] (2
      d3) and 1-d4 show T1min values of 16.5 and 32.6 ms (76.753 MHz), respectively,
      for the rapidly exchanging deuterides. An analogous 2-fold elongation of T1min is
      also observed on going from [(triphos)IrD3] to [(triphos)Ir(eta 2-D2)D2]+. A
      rationale for the elongation of T1min in nonclassical polyhydrides is proposed on
      the basis of both the results obtained and recent literature reports.

PMID- 12526551
TI  - Formation of charge-transfer complexes from neutral bis(porphyrin) sandwiches.
AB  - Lanthanide(III) bis(porphyrin) sandwich complexes of octaethyltetraazaporphyrin
      (OETAP) were synthesized and characterized by UV-vis, IR, and NMR spectroscopies.
      Cyclic voltammetry results indicate that these neutral sandwich complexes are
      very easily reduced. Charge-transfer reactions were performed in solution with Ln
      (OETAP)2 sandwiches and zirconium(IV) bis(porphyrin) sandwiches. The lanthanide
      sandwiches partially oxidize the zirconium sandwiches in solution, and a solvent
      dependence of the charge-transfer reaction was observed. The solid-state
      properties of these charge-transfer materials were also studied. Magnetic
      susceptibility results suggest weak intermolecular interactions between the
      sandwiches. The conductivities of the charge-transfer species are greatly
      improved relative to those of the insulating undoped sandwiches, but the
      conductivities are in the lower semiconducting region. The low conductivity
      values are thought to be due to poor intermolecular overlap.

PMID- 12526552
TI  - Two new one-dimensional compounds with end-to-end dicyanamide as a bridging
      ligand: syntheses and structural characterization of trans-[Mn(4
      bzpy)2(N(CN)2)2]n and cis-[Mn(Bpy)(N(CN)2)2]n, (4-bzpy = 4-benzoylpyridine; bpy =
      2,2'-bipyridyl).
AB  - Two new one-dimensional compounds, trans-[Mn(4-bzpy)2(N(CN)2)2]n (1) and cis
      [Mn(bpy)(N(CN)2)2]n (2), have been synthesized and studied from a magnetic point
      of view (4-bzpy = 4-benzoylpyridine; bpy = 2,2'-bipyridyl). The crystal
      structures of 1 and 2 have been solved. Compound 1 crystallizes in the monoclinic
      system, P2(1)/n group, a = 6.374(2) A, b = 7.584(2) A, c = 26.766(5) A, beta =
      91.87 degrees, and Z = 2, whereas compound 2 crystallizes in the monoclinic
      system, C2/c group, a = 6.707(2) A, b = 17.188(5) A, c = 13.096(5) A, beta =
      90.54 degrees, and Z = 4. The two compounds consist of chains with double mu 1,5
      dicyanamide bridges between neighboring manganese(II) atoms. The weak
      antiferromagnetic coupling found for the two compounds (J = -0.3 cm-1 for 1 and 
      0.4 cm-1 for 2) has been studied by MO analysis, and the superexchange pathway
      through the mu 1,5-(NCNCN-) bridge has been compared with the shorter mu 1,3-(NNN
      ).

PMID- 12526553
TI  - Synthesis and characterization of square planar nickel(II)-arylthiolate complexes
      with the biphenyl-2,2'-dithiolate ligand.
AB  - Two new NiIIS4 complexes with the biphenyl-2,2'-dithiolate ligand (L) are
      reported. The dinuclear complex 1, [Ni2L3]2-, was formed in the reaction of 2-3
      equiv of Na2L and [NiCl4]2- and the mononuclear complex [NiL2]2- (2) by using 4
      10 equiv of Na2L. Complexes 1 and 2 have been crystallographically characterized.
      (Et4N)2[1].0.5S2Ph2, CH3CN: C60H71N3Ni2S7, triclinic, P1, a = 13.806(2) A, b =
      14.267(2) A, c = 16.873(2) A, alpha = 69.263(10) degrees, beta = 69.267(8)
      degrees, gamma = 83.117(10) degrees, Z = 2, R1 = 0.0752 (wR2 = 0.2011).
      (Et4N)(Na.CH3CN)[2]: C34H39N2NaNiS4, triclinic, P1, a = 9.9570(10) A, b =
      13.2670(10) A, c = 13.9560(10) A, alpha = 108.489(7) degrees, beta = 90.396(6)
      degrees, gamma = 103.570(4) degrees, Z = 2, R1 = 0.0390 (wR2 = 0.0995). Both
      complexes are square planar about the nickel ion in the solid state as well as in
      solution. Most Ni(II)-thiolate complexes are square planar except the tetrahedral
      mononuclear complexes with monodentate arylthiolate ligands that cannot force a
      square planar geometry. The ligand (L) has some flexibility to change its bite
      angle via the phenyl-phenyl bond and should not force a planar geometry on its
      complexes either. Therefore, it is interesting that 2 has adopted a square planar
      structure. Complex 2 readily converts to 1 in solution when not in the presence
      of excess L in a process that is presumably similar to that known for other
      mononuclear, bidentate ligated Ni(II) complexes. Both complexes, at least in the
      solid state, appear to have an inclination to bind another metal ion on one face
      of the complex (Ni2+ in 1, Na+ in 2). We hope to take advantage of this in future
      work to synthesize relevant model complexes for the active sites of the nickel
      iron hydrogenases after suitable modifications are made to L.

PMID- 12526554
TI  - Synthesis and structure of organic-soluble binuclear molecular phosphonates of
      tantalum, molybdenum, and tungsten.
AB  - The reaction of (eta 5-C5Me5)TaMe4 with tert-butylphosphonic acid leads to the
      formation of a mixture of compounds: [[(eta 5-C5Me5)TaMe][t-BuP(O)(OH)][t
      BuP(O)(OH)2]]2(t-BuPO3)2 (1) and [[(eta 5-C5Me5)Ta][t-BuP(O)(OH)2]]2(t-BuPO3)2(mu
      O)2 (2). Compound 2 was also obtained by recrystallization of 1 from a THF/hexane
      mixture. Reaction of (eta 5-C5Me5)MCl4 (M = Mo, W) with PhP(O)(OH)2 yields the
      binuclear phosphonates [[(eta 5-C5Me5)M][PhP(O)(OH)2]]2(PhPO3)2(mu-O)2 (M = Mo
      (3); M = W (4)). Compounds 2.THF and 3(.)2.5THF were characterized by single
      crystal X-ray studies. The tantalum and molybdenum phosphonates 2.THF and
      3(.)2.5THF have different structures as compared to those of the previously
      reported titanophosphonate cages.

PMID- 12526555
TI  - Icosahedron oligomerization and condensation in intermetallic compounds. Bonding
      and electronic requirements.
AB  - Icosahedron-based clustering has been found to be very common in intermetallics,
      particularly for group 13 and early p-block icosogen elements. Linking of the
      icosahedral building blocks depends on the valence electron concentrations.
      Vertex-, edge-, or face-sharing icosahedra occur as the structure compensates for
      electron deficiency. Some examples of icosahedron-based clusters have been
      selected for an analysis of the relationships between the structural features
      (icosahedron oligomerization, atomic defects, etc.) and the bonding and
      electronic requirements. The extended Huckel method has been used with either a
      molecular approach or an electronic band structure calculation to rationalize
      bonding in the intermetallic framework.

PMID- 12526556
TI  - Eight- and 16-membered cyanuric-sulfanuric ring systems: C2N4S2-->C2N3S ring
      contraction.
AB  - Eight- and 16-membered cyanuric-sulfanuric ring systems of the type
      Ar2C2N4S2(O)2Ar'2 (3a, Ar = 4-BrC6H4, Ar' = Ph; 3b, Ar = 4-CF3C6H4, Ar' = Ph; 3c,
      Ar = 4-CF3C6H4, Ar' = 4-CH3C6H4) and Ar4C4N8S4(O)4Ar'4 (4b, Ar = 4-CF3C6H4, Ar' =
      Ph; 4c, Ar = 4-CH3C6H4, Ar' = Ph; 4d, Ar = 4-CF3C6H4, Ar' = 4-CH3C6H4),
      respectively, were prepared in good yields by the reaction of the corresponding
      sulfur(IV) systems with m-chloroperbenzoic acid. The X-ray structures of 3b,
      3c.C7H14, 4b.CH2Cl2, 4c, and the S(IV) system Ar4C4N8S4Ar'4 (2c, Ar = 4-CH3C6H4,
      Ar' = Ph) were determined. Upon oxidation the two oxygen atoms in 3b and 3c.C7H14
      adopt endo positions leading to a twist boat conformation for the C2N4S2 ring.
      The 16-membered C4N8S4 rings in 4b and 4c retain a cradle conformation upon
      oxidation. The S-N bond distances are ca. 0.06 A shorter in all the S(VI) systems
      compared to those in the corresponding S(IV) rings. The thermolysis of 3b at ca.
      220 degrees C occurs primarily via loss of a sulfanuric group, NS(O)Ph, to give
      the six-membered ring (4-CF3C6H4)2C2N3S(O)Ph (6). The structure of 6 was
      confirmed by X-ray crystallography. Crystal data: 2c, triclinic, space group P1
      with a = 13.917(2) A, b = 15.610(4) A, c = 13.491(3) A, alpha = 95.77(2) degrees,
      beta = 114.82(1) degrees, gamma = 76.21(2) degrees, V = 2583(1) A3, and Z = 2;
      3b, monoclinic, space group P2(1)/a with a = 7.316(2) A, b = 29.508(5) A, c =
      12.910(2) A, beta = 101.30(2) degrees, V = 2733(1) A3, and Z = 4; 3c.C7H14,
      triclinic, space group P1 with a = 12.849(4) A, b = 12.863(4) A, c = 12.610(7) A,
      alpha = 110.61(3) degrees, beta = 105.77(3) degrees, gamma = 62.77(2) degrees, V
      = 1719(1) A3, and Z = 2; 4b.CH2Cl2, triclinic, space group P1 with a = 12.647(3)
      A, b = 19.137(3) A, c = 12.550(2) A, alpha = 105.765(11) degrees, beta =
      93.610(15) degrees, gamma = 88.877(16) degrees, V = 2917.2(9) A3, and Z = 2; 4c,
      orthorhombic, space group Pba2 with a = 22.657(2) A, b = 10.570(2) A, c =
      10.664(3) A, alpha = beta = gamma = 90 degrees, V = 2554(1) A3, and Z = 2; 6,
      triclinic, space group P1 with a = 7.4667(8) A, b = 11.3406(12) A, c =
      13.5470(14) A, alpha = 108.000(2) degrees, beta = 105.796(2) degrees, gamma =
      94.300(2) degrees, V = 1033.8(2) A3, and Z = 2.

PMID- 12526557
TI  - Syntheses and structures of quinuclidine-stabilized amido- and azidogallanes.
AB  - Quinuclidine-stabilized amido- and azidogallanes, HGa[N(TMS)2]2(quin) (1),
      H2Ga[N(TMS)2](quin) (2), HGa-[N(H)(2,6-iPr2C6H3)]2(quin) (3), and H2GaN3(quin)
      (4), were synthesized from the quinuclidine adducts of mono- and dichlorogallane.
      Structural determinations revealed that all compounds were monomeric with four
      coordinate gallium centers. Reactions of the five-coordinate compound,
      HGaCl2(quin)2, with 2 equiv of Li[N(TMS)2] or Li[N(H)(2,6-iPr2C6H3)] resulted in
      the isolation of compound 1 or 3. A ligand redistribution during the reaction of
      H2GaCl(quin) with Li[N(H)(2,6-iPr2C6H3)] produced compound 3 and H3Ga(quin) in a
      1:1 molar ratio.

PMID- 12526558
TI  - Equilibrium and kinetic studies of the aquation of the dinuclear platinum complex
      [[trans-PtCl(NH3)2]2(mu-NH2(CH2)6NH2)]2+: pKa determinations of aqua ligands via
      [1H,15N] NMR spectroscopy.
AB  - By the use of [1H,15N] heteronuclear single quantum coherence (HSQC) 2D NMR
      spectroscopy and electrochemical methods we have determined the hydrolysis
      profile of the bifunctional dinuclear platinum complex [[trans-PtCl(15NH3)2]2(mu
      15NH2(CH2)(6)15NH2)]2+ (1,1/t,t (n = 6), 15N-1), the prototype of a novel class
      of potential antitumor complexes. Reported are estimates for the rate and
      equilibrium constants for the first and second aquation steps, together with the
      acid dissociation constant (pKa1 approximately pKa2 approximately pKa3). The
      equilibrium constants determined by NMR at 25 and 37 degrees C (I = 0.1 M) were
      similar, pK1 approximately pK2 = 3.9 +/- 0.2, and from a chloride release
      experiment at 37 degrees C the values were found to be pK1 = 4.11 +/- 0.05 and
      pK2 = 4.2 +/- 0.5. The forward and reverse rate constants for aquation determined
      from this chloride release experiment were k1 = (8.5 +/- 0.3) x 10(-5) s-1 and k
      1 = 0.91 +/- 0.06 M-1 s-1, where the model assumed that all the liberated
      chloride came from 1. When the second aquation step was also taken into account,
      the rate constants were k1 = (7.9 +/- 0.2) x 10(-5) s-1, k-1 = 1.18 +/- 0.06 M-1
      s-1, k2 = (10.6 +/- 3.0) x 10(-4) s-1, k-2 = 1.5 +/- 0.6 M-1 s-1. The rate
      constants compare favorably with other complexes with the [PtCl(am(m)ine)3]+
      moiety and indicate that the equilibrium of all these species favors the chloro
      form. A pKa value of 5.62 was determined for the diaquated species [[trans
      Pt(15NH3)2(H2O)]2(mu-15NH2(CH2)(6)15NH2)]4+ (3) using [1H,15N] HSQC NMR
      spectroscopy. The speciation profile of 1 and its hydrolysis products under
      physiological conditions is explored.

PMID- 12526559
TI  - Synthesis and crystal structure of a novel germanate:
      (NH4)4[(GeO2)3(GeO1.5F3)2].0.67H2O.
AB  - The novel microporous germanate (NH4)4[(GeO2)3(GeO1.5F3)2].0.67H2O was prepared
      from an aqueous solution containing germanium dioxide, pyridine, hydrofluoric
      acid, and 2,6-diaminopyridine as a template. The solution was kept at 165 degrees
      C in a Teflon-lined autoclave for 4 days. Large crystals were produced and
      studied by X-ray powder diffraction, FTIR, thermal analysis, and elemental
      analysis. The structure was determined by single-crystal X-ray diffraction. The
      crystal is orthorhombic, space group Pbcn, with a = 7.0065(4) A, b = 11.7976(6)
      A, c = 19.5200(14) A, and Z = 4. The structure is a layered framework built up
      from GeO4 tetrahedral and GeO3F3 octahedral units. The polyhedral units are
      connected in such a way that they form a zeolite-like porous structure with three
      and nine-membered rings. Half of the ammonium ions are located inside the nine
      membered rings. The other half are above and below the three-membered rings. The
      connectivity of the germanium polyhedral units is interrupted along the c axis by
      ammonium ions and water molecules inserted between the layers.

PMID- 12526560
TI  - Kinetics and mechanism of complex formation of nickel(II) with tetra-N-alkylated
      cyclam in N,N-dimethylformamide (DMF): comparative study on the reactivity and
      solvent exchange of the species Ni(DMF)6(2+) and Ni(DMF)5Cl+.
AB  - 13C NMR was used to study the rate of DMF exchange in the nickel(II) cation
      Ni(DMF)6(2+) and in the monochloro species Ni(DMF)5Cl+ with 13C-labeled DMF in
      the temperature range of 193-395 K in DMF (DMF = N,N-dimethylformamide). The
      kinetic parameters for solvent exchange are kex = (3.7 +/- 0.4) x 10(3) s-1,
      delta H++ = 59.3 +/- 5 kJ mol-1, and delta S++ = +22.3 +/- 14 J mol-1 K-1 for
      Ni(DMF)6(2+) and kex = (5.3 +/- 1) x 10(5) s-1, delta H++ = 42.4 +/- 4 kJ mol-1,
      and delta S++ = +6.7 +/- 15 J mol-1 K-1 for Ni(DMF)5Cl+. Multiwavelength stopped
      flow spectrophotometry was used to study the kinetics of complex formation of the
      cation Ni(DMF)6(2+) and of the 100-fold more labile cation Ni(DMF)5Cl+ with TMC
      (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and TEC (1,4,8,11
      tetraethyl-1,4,8,11-tetraazacyclotetradecane) in DMF at 298 K and I = 0.6 M
      (tetra-n-butylammoniumperchlorate). Equilibrium constants K for the addition of
      the nucleophiles DMF, Cl-, and Br- to the complexes Ni(TMC)2+ and Ni(TEC)2+ were
      determined by spectrophotometric titration. Formation of the complexes Ni(TMC)2+
      and Ni(TEC)2+ was found to occur in two stages. In the initial stage, fast,
      second-order nickel incorporation with rate constants k1(TMC) = 99 +/- 5 M-1 s-1
      and k1 (TEC) = 235 +/- 12 M-1 s-1 leads to the intermediates Ni(TMC)int2+ and
      Ni(TEC)int2+, which have N4-coordinated nickel. In the second stage, these
      intermediates rearrange slowly to form the stereochemically most stable
      configuration. First-order rate constants for the one-step rearrangement of
      Ni(TMC)int2+ and the two-step rearrangment of Ni(TEC)int2+ are presented. Because
      of the rapid formation of Ni(DMF)5Cl+, the reactions of Ni(DMF)6(2+) with TMC and
      TEC are accelerated upon the addition of tetra-n-butylammoniumchloride (TBACl)
      and lead to the complexes Ni(TMC)Cl+ and Ni(TEC)Cl+, respectively. For initial
      concentrations such that [TBACl]o/[nickel]o > or = 20, intermediate formation is
      230 times (TMC) and 47 times (TEC) faster than in the absence of chloride. The
      mechanism of complex formation is discussed.

PMID- 12526561
TI  - Kinetics and mechanism for reduction of the anticancer prodrug trans,trans,trans
      [PtCl2(OH)2(c-C6H11NH2)(NH3)] (JM335) by thiols.
AB  - The reduction of the platinum(IV) prodrug trans,trans,trans-[PtCl2(OH)2(c
      C6H11NH2)(NH3)] (JM335) by L-cysteine, DL-penicillamine, DL-homocysteine, N
      acetyl-L-cysteine, 2-mercaptopropanoic acid, 2-mercaptosuccinic acid, and
      glutathione has been investigated at 25 degrees C in a 1.0 M aqueous perchlorate
      medium with 6.8 < or = pH < or = 11.2 using stopped-flow spectrophotometry. The
      stoichiometry of Pt(IV):thiol is 1:2, and the redox reactions follow the second
      order rate law -d[Pt(IV)]/dt = k[Pt(IV)][RSH]tot, where k denotes the pH
      dependent second-order rate constant and [RSH]tot the total concentration of
      thiol. The pH dependence of k is ascribed to parallel reductions of JM335 by the
      various protolytic species of the thiols, the relative contributions of which
      change with pH. Electron transfer from thiol (RSH) or thiolate (RS-) to JM335 is
      suggested to take place as a reductive elimination process through an attack by
      sulfur at one of the mutually trans chloride ligands, yielding trans-[Pt(OH)2(c
      C6H11NH2)(NH3)] and RSSR as the reaction products, as confirmed by 1H NMR. Second
      order rate constants for the reduction of JM335 by the various protolytic species
      of the thiols span more than 3 orders of magnitude. Reduction with RS- is
      approximately 30-2000 times faster than with RSH. The linear correlation log(kRS)
      = (0.52 +/- 0.06)-pKRSH--(2.8 +/- 0.5) is observed, where kRS denotes the second
      order rate constant for reduction of JM335 by a particular thiolate RS- and KRSH
      is the acid dissociation constant for the corresponding thiol RSH. The slope of
      the linear correlation indicates that the reactivity of the various thiolate
      species is governed by their proton basicity, and no significant steric effects
      are observed. The half-life for reduction of JM335 by 6 mM glutathione (40-fold
      excess) at physiologically relevant conditions of 37 degrees C and pH 7.30 is 23
      s. This implies that JM335, in clinical use, is likely to undergo in vivo
      reduction by intracellular reducing agents such as glutathione prior to binding
      to DNA. Reduction results in the immediate formation of a highly reactive
      platinum(II) species, i.e., the bishydroxo complex in rapid protolytic
      equilibrium with its aqua form.

PMID- 12526563
TI  - Heteronuclear chains of four metal atoms including one quadruply bonded dimetal
      unit. Dichromium and dimolybdenum compounds with appended copper(I) atoms.
AB  - It is shown that the M2(DPhIP)4 molecules (M = Cr, Mo; HDPhIP = 2,6
      di(phenylimino)piperidine) can each capture two CuI atoms to form molecules with
      linear Cu...M[symbol: see text] M...Cu chains. In these chains the CuI atoms have
      only weak interactions with the M atoms (Cr...Cu = 2.628 A; Mo...Cu = 2.615 A)
      even though their introduction causes marked decreases in the M[symbol: see
      text]M distances (from 2.265 to 1.906 A for Cr and from 2.114 to 2.078 A for Mo).
      These seemingly contradictory facts are explained by noting that in the
      M2(DPhIP)4 molecules there are strong destabilizing (to the M[symbol: see text]M
      bonds) donor interactions of the dangling nitrogen atoms with the pi* orbitals.
      When these are eliminated by the introduction of the CuI atoms, the M[symbol: see
      text]M bonds become stronger and shorter.

PMID- 12526562
TI  - Weakly coordinating anions HA2-generated from oxoanions A- and their conjugate
      acids. Coordination equilibria, ionic conductivities, and the structures of
      [Cu2(H(CH3SO3)2)4]n and [Cu(CO)(H(CF3CO2)2)]2.
AB  - The coordination or ion pairing of the hydrogen-bonded anions H(CF3CO2)2- and
      H(CH3SO3)2- to NEt4+, Li+, Cu+, and/or Cu2+ was investigated. The structure of
      [Cu2(H(CH3SO3)2)4]n consists of centrosymmetric dimeric moieties that contain two
      homoconjugated (CH3SO2O-H...OSO2CH3)- anions per Cu2+ ion, forming typical Jahn
      Teller tetragonally elongated CuO6 coordination spheres. The oxygen atoms
      involved in the nearly linear O-H...O hydrogen bonds (O...O approximately 2.62 A)
      are not coordinated to the Cu2+ ions. The structure of Cu2(CO)2(H(CF3-CO2)2)2
      consists of pseudo-C2-symmetric dimers that contain one homoconjugated (CF3COO
      H...OCOCF3)- anion per Cu+ ion, forming highly distorted tetrahedral Cu(CO)O3
      coordination spheres. Three of the four oxygen atoms in each hydrogen-bonded
      H(CF3CO2)2- anion are coordinated to the Cu+ ions, including one of the oxygen
      atoms in each O-H...O hydrogen bond (O...O approximately 2.62 A). Infrared
      spectra (v(CO) values) of Cu(CO)(CF3CO2) or Cu(CO)(CH3SO3) dissolved in
      acetonitrile or benzene, with and without added CF3COOH or CH3SO3H, respectively,
      demonstrate that HA2- anions involving carboxylates or sulfonates are more weakly
      coordinating than the parent anions RCO2- and RSO3-. Direct current
      conductivities of THF solutions of Li(CF3CO2) containing varying concentrations
      of added CF3COOH further demonstrate that Li+ and NEt4+ ion pair much more weakly
      with H(CF3CO2)2- than with CF3CO2-.

PMID- 12526564
TI  - Studies of dirhodium(II) tetra(trifluoroacetate). 5. Remarkable examples of the
      ambidentate character of dimethyl sulfoxide.
AB  - The ambidentate character of dimethyl sulfoxide, already known for dirhodium
      carboxylates, has been remarkably manifested in new ways. Three novel complexes
      of dirhodium(II) tetra(trifluoroacetate) with the DMSO ligand, namely,
      [Rh2(O2CCF3)4]m(DMSO)n with m:n = 7:8 (1), 1:1 (2), and 3:2 (3), have been
      obtained by deposition from the vapor phase, and their crystal structures have
      been determined by X-ray crystallography. The crystallographic parameters are as
      follows: for 1, monoclinic space group P2(1)/c with a = 28.261(2) A, b =
      16.059(4) A, c = 17.636(2) A, beta = 92.40(4) degrees, and Z = 2; for 2,
      triclinic space group P1 with a = 8.915(2) A, b = 10.592(2) A, c = 11.916(2) A,
      alpha = 84.85(1) degrees, beta = 88.86(1) degrees, and gamma = 65.187(8) degrees,
      and Z = 2; and for 3, triclinic space group P1 with a = 8.876(2) A, b = 9.017(2)
      A, c = 19.841(3) A, alpha = 101.91(2) degrees, beta = 97.144(8) degrees, gamma =
      100.206(9) degrees, and Z = 1. In the oligomeric molecule of 1, six DMSO ligands
      bridge seven dirhodium tetra(trifluoroacetate) units in a bidentate fashion via S
      and O atoms, and two additional DMSO molecules terminate the chain. In the
      structure of the monoadduct Rh2(O2CCF3)4(DMSO) (2), the dirhodium blocks are
      bridged through the O atoms of DMSO ligands, forming a one-dimensional polymeric
      chain. Compound 3 also has an infinite chain structure with the molecules of
      dimethyl sulfoxide acting in a bidentate mu-DMSO-S,O mode. Every second DMSO
      molecule is missing in 3, so that two of every three Rh2(O2CCF3)4 units are
      associated through the O atoms of carboxylate groups to give the overall
      composition [Rh2(O2CCF3)4]3(DMSO)2.

PMID- 12526565
TI  - The CrIIL reduction of [2Fe-2S] ferredoxins and site of attachment of CrIII using
      1H NMR and site-directed mutagenesis.
AB  - The recently reported NMR solution structure of FeIIIFeIII parsley FdI has made
      possible 2D NOESY NMR studies to determine the point of attachment of CrIIIL in
      FeIIIFeIII...CrIIIL. The latter Cr-modified product was obtained by reduction of
      FeIIIFeIII parsley and spinach FdI forms with [Cr(15-aneN4) (H2O)2]2+ (15-aneN4 =
      1,4,8,12-tetraazacyclopentadecane), referred to here as CrIIL, followed by air
      oxidation and chromatographic purification. From a comparison of NMR cross-peak
      intensities of native and Cr-modified proteins, two surface sites designated A
      and B, giving large paramagnetic CrIIIL broadening of a number of amino acid
      peaks, have been identified. The effects at site A (residues 19-22, 27, and 30)
      are greater than those at site B (residues 92-94 and 96), which is on the
      opposite side of the protein. From metal (ICP-AES) and electrospray ionization
      mass spectrometry (EIMS) analyses on the Cr-modified protein, attachment of a
      single CrIIIL only is confirmed for both parsley and spinach FdI and FdII
      proteins. Electrostatic interaction of the 3+ CrIIIL center covalently attached
      to one protein molecule (charge approximately -18) with a second (like) molecule
      provides an explanation for the involvement of two regions. Thus for 3-4 mM
      FeIIIFeIII...CrIIIL solutions used in NMR studies (CrIIIL attached at A),
      broadening effects due to electrostatic interactions at B on a second molecule
      are observed. Experiments with the Cys18Ala spinach FdI variant have confirmed
      that the previously suggested Cys-18 at site A is not the site of CrIIIL
      attachment. Line broadening at Val-22 of A gives the largest effect, and CrIIIL
      attachment at one or more adjacent (conserved) acidic residues in this region is
      indicated. The ability of CrIIL to bind in some (parsley and spinach) but not all
      cases (Anabaena variabilis) suggests that intramolecular H-bonding of acidic
      residues at A is relevant. The parsley and spinach FeIIFeIII...CrIIIL products
      undergo a second stage of reduction with the formation of FeIIFeII...CrIIIL.
      However, the spinach Glu92Ala (site B) variant undergoes only the first stage of
      reduction, and it appears that Glu-92 is required for the second stage of
      reduction to occur. A sample of CrIIIL-modified parsley FeIIIFeIII Fd is fully
      active as an electron carrier in the NADPH-cytochrome c reductase reaction
      catalyzed by ferredoxin-NADP+ reductase.

PMID- 12526566
TI  - Emission and metal- and ligand-centered-redox characteristics of the
      hexarhenium(III) clusters trans- and cis-[Re6(mu 3-S)8Cl4(L)2]2-, where L is a
      pyridine derivative or pyrazine.
AB  - Preparations of a series of face-capped octahedral hexarhenium(III) clusters
      having two N-heterocyclic ligands, [Bu4N]2[trans-[Re6(mu 3-S)8Cl4(L)2]] (Bu4N+ =
      tetra-n-butylammonium cation; L = pyrazine (1a), 4,4'-bipyridine (3a), 4
      methylpyridine (5a), 4-(dimethylamino)pyridine (6a)) and their cis analogues (1b,
      3b, 5b, and 6b, respectively), and their electrochemical and photophysical
      properties have been reported. An X-ray crystal structure determination has been
      carried out for 1a to confirm the trans configuration (C40H80N6S8Cl4Re6,
      orthorhombic, space group Cmca (No. 64), a = 19.560(5) A, b = 19.494(4) A, c =
      18.592(4) A, beta = 115.76(2) degrees, Z = 4). The redox potential of the
      reversible ReIII6/ReIII5ReIV process of these complexes and previously reported
      [Bu4N]2[trans- and cis-[Re6(mu 3-S)8Cl4(4-cyanopyridine)2]] (2a and 2b,
      respectively) and [Bu4N]2[trans- and cis-[Re6(mu 3-S)8Cl4(pyridine)2]] (4a and
      4b, respectively) in acetonitrile depends linearly on the pKa of the N
      heterocyclic ligands, with the potentials being more negative with basic ligands.
      The ligand-centered-redox waves for 1a, 1b, 2a, and 2b were observed as split
      waves (delta E1/2 = 90-140 mV), the extent of the splitting being larger for the
      cis isomer and largest for the pyrazine complexes. Electronic interaction between
      the two ligands through the [Re6(mu 3-S)8]2+ core has been suggested. The second
      ligand-reduction wave was also observed for 3a and 3b, the potential being
      shifted positively to coalesce with the first reduction wave on addition of the
      weak proton donor imidazole. This is accounted for by the proton-coupled redox
      reaction at the free pyridyl site of the 4,4'-bipyridine ligands. All of the
      complexes show luminescence in acetonitrile at room temperature. While the
      complexes of pyridine and 4-methylpyridine show photophysical characteristics
      (lambda em 740-750 nm, phi em 0.031-0.057, tau em 4.2-6.2 microseconds) similar
      to those (770 nm, 0.039, and 6.3 microseconds, respectively) of [Re6(mu 3
      S)8Cl6]4-, emissions of other complexes are significantly weak with lambda em,
      phi em, and tau em values in the ranges 763-785 nm, 0.0010-0.0017, and 0.013
      0.029 microsecond, respectively. Suggestions are given for the excited states
      localized on the cluster core and the ligand pi* orbitals.

PMID- 12526567
TI  - Novel gallium phosphate framework encapsulating trinuclear Mn3(H2O)6O8 cluster:
      hydrothermal synthesis and characterization of Mn3(H2O)6Ga4(PO4)6.
AB  - A new manganese gallium phosphate, Mn3(H2O)6Ga4(PO4)6, has been synthesized under
      hydrothermal conditions at 150 degrees C and characterized by single-crystal X
      ray diffraction, thermogravimetric analysis, magnetic susceptibility, and
      electron paramagnetic resonance (EPR) spectroscopy. It crystallized in the
      monoclinic space group, P2(1)/n, with a = 8.9468(4) A, b = 10.148(5) A, c =
      13.5540(7) A, beta = 108.249(1) degrees, and Z = 2. The compound is unusual in
      that it is not only the first nonoranically templated MnGaPO phase but also the
      first instance where edge-shared trinuclear manganese-oxygen clusters are
      encapsulated in a metal phosphate lattice. The trimer involves a central
      Mn(H2O)4O2 octahedron, which links to two Mn (H2O)2O4 octahedra at trans edges.
      The Mn3(H2O)6O8 clusters reside in tunnels built from GaO5 trigonal bipyramids
      and PO4 tetrahedra. Our magnetic study revealed that superexchange interactions
      occurred between the neighboring MnII centers. A good fit of the magnetic
      susceptibility data for the isolated trimers was obtained by using a derived
      expression based on Van Vleck's equation. Unlike all existing linear trinuclear
      MnII complexes, the chi MT product in the range 8-4 K remains at a constant value
      corresponding to one spin S = 5/2 per three MnII centers. The Curie behavior at
      such low temperatures has been confirmed by EPR data. According to the
      thermogravimetric analysis/differential thermal analysis (TGA/DTA) results, the
      title compound is thermally stable up to ca. 200 degrees C.

PMID- 12526569
TI  - C6, C7, and C8 perfluoroalkyl-substituted phosphinic acids.
AB  - Reaction of red phosphorus with RfI in a 1:2 molar ratio at 230 degrees C led to
      the formation of a mixture of (Rf)2PI and (Rf)PI2 (Rf = C6F13, C7F15, C8F17) in
      about a 70:30 ratio, respectively. These mixtures were separated by vacuum
      distillation. (Rf)2PI (Rf = C6F13, C7F15) are yellow liquids whereas (C8F17)2PI
      is a yellow solid. Oxidation of (Rf)2PI with excess NO2 led to (Rf)2P(O)OH (Rf =
      C6F13, C7F15, C8F17) in > 90% isolated yields after aqueous hydrolysis of the
      anhydride intermediates. These highly fluorinated phosphinic acids are white
      solids with sharp melting points and are highly soluble in methyl sulfoxide
      (DMSO) and 1,1,2-trichlorotrifluoroethane. However, solubility in chloroform and
      methylene dichloride is low. These perfluoroalkylphosphinic acids were
      characterized by IR, NMR (1H, 19F, and 31P), and mass spectra and elemental
      analysis.

PMID- 12526568
TI  - Orientation of iron bleomycin and porphyrin complexes on DNA fibers.
AB  - Bleomycin (Blm) is an antitumor agent that requires iron and oxygen for strand
      cleavage of DNA. In this study, ferric bleomycin, Fe(III)Blm, or the nitric oxide
      adduct of ferrous bleomycin, ON-Fe(II)Blm, were bound to one-dimensionally
      oriented DNA fibers. Reductive nitrosylation of Fe(III) complexes took place in
      situ on B-form DNA fibers. Electron paramagnetic resonance (EPR) spectra were
      obtained as a function of the angle phi between the magnetic field B and the
      fiber axis Zf. For comparison, EPR spectra were acquired for ON-Fe(II)TMpyP and
      ON-Fe(II)TMpyP-Im on oriented DNA fibers, where TMpyP is 5,10,15,20-tetrakis(1
      methyl-4-pyridino)porphyrin and Im is imidazole. EPR spectra showed both low-spin
      Fe(III)Blm and ON-Fe(II)Blm bound to B-form DNA in two slightly different binding
      orientations in the ratio of 1:0.2. With A-form DNA, a fraction of bound
      Fe(III)Blm was high spin. Specifically, the angle beta between the fiber axis Zf
      and the g axis, gz, perpendicular to or nearly perpendicular to the equatorial
      plane of the iron complex was estimated as 20 degrees and 25 degrees for ON
      Fe(II)Blm and 30 degrees and 25 degrees for Fe(III)Blm, respectively. The angle
      gamma that determines the orientation of gx and gy axes was estimated as 90
      degrees for the two ON-Fe(II)Blm species and 10 degrees for the two Fe(III)Blm
      species, respectively. The NO was held rigidly in place as the temperature
      increased from 123 K to room temperature for ON-Fe(II)Blm but not for ON
      Fe(II)TMpyP or ON-Fe(II)TMpyP-Im. It is hypothesized that the NO is structurally
      oriented by hydrogen bonding like the peroxide is held in HO2(-)-Co(III)Blm (Wu
      et al. J. Am. Chem. Soc. 1996, 118, 1281-1294). The EPR parameters are consistent
      with a six-coordinate complex for ON-Fe(II)Blm, although the superhyperfine
      structure from the trans nitrogen was not detected. The increase in g value
      anisotropy upon binding ON-Fe(II)Blm to DNA fiber may be caused by an increase in
      the overlap of d pi and 2p pi* orbitals induced by an interaction of NO with DNA
      and/or by a perturbation of d orbitals due to the pyrimidine-guanine interaction.
      It is concluded that the EPR parameters of ON-Fe(II)Blm and Fe(III)Blm bound to
      oriented DNA support the hypothesis that FeBlm species bind to DNA with adduct
      structures similar to those formed by related CoBlm species and DNA.

PMID- 12526570
TI  - Ternary rare-earth selenides with the U3ScS6 structure type: synthesis,
      characterization, and some magnetic properties of Ln3TSe6 (Ln = Sm, Gd; T = In,
      Cr) and Tb3CrSe6.
AB  - The new compounds Ln3TSe6 (Ln = Sm, Gd; T = In, Cr) and Tb3CrSe6 have been
      synthesized by the solid-state reactions of the elements at 850 degrees C. A KBr
      flux was used to promote crystal growth. These isostructural compounds
      crystallize with the U3ScS6 structure type. The crystal structure is built from
      LnSe7 pseudo-octahedra or LnSe8 bicapped trigonal prisms and TSe6 octahedra.
      Magnetic measurements show that Sm3TSe6 (T = In, Cr) and Tb3CrSe6 are
      paramagnetic down to 5 K whereas Gd3CrSe6 undergoes an antiferromagnetic
      transition at 10 K. Crystal data: orthorhombic, Pnnm, Z = 4, T = -120 degrees C,
      (compound, a (A), b (A), c (A))-Sm3InSe6, 14.177(3), 17.352(4), 4.0625(8);
      Gd3InSe6, 14.071(3), 17.286(4), 4.0202(8); Sm3CrSe6, 14.032(3), 16.782(3),
      3.9841(8); Gd3CrSe6, 13.938(3), 16.780(3), 3.9559(8); Tb3CrSe6, 13.885(3),
      16.672(3), 3.9215(8).

PMID- 12526571
TI  - Improved procedures for the generation of diborane from sodium borohydride and
      boron trifluoride.
AB  - Improved procedures for the generation of diborane by the reaction of NaBH4 in
      triglyme or tetraglyme with the BF3 adducts of di-n-butyl ether, tert-butyl
      methyl ether, monoglyme, dioxane, and tetrahydropyran were developed. In these
      systems, generation of diborane requires 2-4 h at 25 degrees C (faster reactions
      take place at 50 degrees C). The byproduct NaBF4 precipitates from the reaction
      mixture at 25 degrees C as the reaction proceeds. The high-boiling glyme can be
      conveniently separated from the lower boiling carrier ethers by simple
      distillation of the latter. On the other hand, diborane was generated very slowly
      or not generated using the addition of each of six boron trifluoride-etherates
      (di-n-butyl ether, tert-butyl methyl ether, tetrahydrofuran, tetrahydropyran,
      dioxane, and monoglyme) to suspensions of sodium borohydride in the corresponding
      ether. However, diborane was generated rapidly and quantitatively by the addition
      of NaBH4 in triglyme (or tetraglyme) to the BF3 adduct of triglyme (or
      tetraglyme) at room temperature. No solid precipitation occurs during the
      reaction, making it convenient for large-scale applications. The pure solvent
      triglyme (or tetraglyme) can be easily recovered and recycled by either
      crystallizing or precipitating NaBF4 from the generation flask. New procedures
      for the generation of diborane were also developed by the reaction of NaBF4 with
      NaBH4 in triglyme (or tetraglyme) in the presence of Lewis acids such as AlCl3
      and BCl3.

PMID- 12526572
TI  - Synthesis, X-ray powder structure, and magnetic properties of the new, weak
      ferromagnet iron(II) phenylphosphonate.
AB  - A new molecule-based weak ferromagnet of formula Fe[C6H5PO3].H2O was synthesized.
      It was characterized by thermogravimetric analysis and UV-visible and infrared
      spectroscopy, and the magnetic properties were studied using a superconducting
      quantum interference device magnetometer. The crystal structure of the compound
      was determined "ab initio" from X-ray powder diffraction data and refined by the
      Rietveld method. The crystals of Fe[C6H5PO3].H2O are orthorhombic, space group
      Pmn2(1), with a = 5.668(8) A, b = 14.453(2) A, c = 4.893(7) A, and Z = 2. The
      title compound is isostructural with the previously reported lamellar
      M[C6H5PO3].H2O, M = Mn(II), Zn(II), and Cd(II). The inorganic layers are made of
      Fe(II) ions octahedrally coordinated by five phosphonate oxygen atoms and one
      from oxygen of the water molecule. These layers are then separated by bilayers of
      the phenyl groups, and van der Waals contacts are established between them. The
      refinement has shown that the phenyl rings are disordered in the lattice. The
      oxidation state of the metal ion is +2, and the electronic configuration is d6 (S
      = 2) high-spin, as determined from dc magnetic susceptibility measurements from
      150 K to room temperature. Below 100 K, the magnetic moment of Fe[C6H5PO3].H2O
      rises rapidly to a maximum at TN = 21.5 K, and then it decreases again. The peak
      at TN is associated with the 3D antiferromagnetic long-range ordering. Below the
      critical temperature, the title compound behaves as a "weak" ferromagnet, which
      represents the third type of magnetic materials characterized by having a finite
      zero-field magnetization, ferromagnets and ferrimagnets being the other two
      types. The large coercive field (i.e., 6400 G) observed in the hysteresis loop at
      T = 10 K is rare in molecule-based materials; it can be ascribed to a pronounced
      spin-orbit coupling for the 5T2g ground state of the Fe(II) ion in the octahedral
      environment.

PMID- 12526573
TI  - Layered K4[Re6S10(CN)2] and chainlike K4[Re6Se10(CN)4]: new types of
      chalcocyanide cluster compounds with bridging chalcogenide ligands.

PMID- 12526574
TI  - Hydrogen-deuterium exchange in decaborane(14): mechanistic studies.

PMID- 12526575
TI  - An inorganic application of transient direct current photoconductivity:
      corroboration of a charge-transfer assignment for the luminescing states of
      Pt(dpphen)(ecda)1.

PMID- 12526576
TI  - Transient DC photocurrent investigation of charge redistribution within
      Re(CO)3Cl(2,2'-bipyridine): an unexpected decrease in molecular dipole moment
      upon emissive excited-state formation.

PMID- 12526577
TI  - Synthesis and structural characterization of a new open-framework tin(II)
      phosphate: [Sn4(PO4)3]-.0.5[C4N2H12]2+.

PMID- 12526578
TI  - Complexation of Co(DBF2)2 by N-methylimidazole in acetonitrile: formation
      constants and 1H NMR shifts and relaxation times.

PMID- 12526579
TI  - Nanophase cobalt oxyhydroxide mineral synthesized within the protein cage of
      ferritin.

PMID- 12526580
TI  - Polynuclear carboxylato-bridged iron(II) clusters: synthesis, structure, and host
      guest chemistry.

PMID- 12526581
TI  - Embracing diversity and unity.

PMID- 12526582
TI  - Marion's message. A distant dream of unity.

PMID- 12526583
TI  - Is unity possible in this diverse midwifery community?

PMID- 12526584
TI  - Unity. An elusive but necessary goal for U.S. midwives and their advocates.

PMID- 12526585
TI  - Unity from the inside out.

PMID- 12526586
TI  - Midwifery unity. Let's grow with our clients.

PMID- 12526587
TI  - United we stand.

PMID- 12526588
TI  - Childbirth and the responsibility of choice.

PMID- 12526589
TI  - Priorities in birth.

PMID- 12526590
TI  - My dream.

PMID- 12526591
TI  - Ultrasound revisited.

PMID- 12526592
TI  - Ultrasound scans: cause for concern.

PMID- 12526593
TI  - More about unassisted birth.

PMID- 12526594
TI  - The midwife who can't get pregnant.

PMID- 12526595
TI  - Uncertainties about SIDS.

PMID- 12526596
TI  - The new, improved worries of pregnancy.

PMID- 12526597
TI  - Reaching out to the next generation. Interview by Mary Kroeger.

PMID- 12526598
TI  - Journeys through old and new in south India.

PMID- 12526599
TI  - Humanization of childbirth in Bolivia.

PMID- 12526600
TI  - Intersections. The evolution of health care in a rural minority village of
      Vietnam.

PMID- 12526601
TI  - Can dental education be saved?

PMID- 12526602
TI  - Freedom movement. The state of the licensing by credentials debate.

PMID- 12526603
TI  - Simple steps to prevent bad breath.

PMID- 12526604
TI  - Dysfunctional uterine bleeding. Principles of diagnosis and management.

PMID- 12526605
TI  - Taking the lead. NPs emerge as experts in 2002.

PMID- 12526607
TI  - Seize the moment. Examination of the asymptomatic diabetic foot.

PMID- 12526606
TI  - After the NICU. Comprehensive primary care for preterm infants.

PMID- 12526608
TI  - Outcome-based outpatient education. Proving our cost-effectiveness and more.

PMID- 12526610
TI  - Patient information. Feeling SAD?

PMID- 12526609
TI  - Back in the game. Preventing and treating athletic injuries in adolescents.

PMID- 12526611
TI  - Bathing aid options.

PMID- 12526612
TI  - Frankenstein's foot.

PMID- 12526613
TI  - Developing new nurses: a nurse extern's experience.

PMID- 12526614
TI  - Use of ratios in financial statement analysis.

PMID- 12526615
TI  - Optimizing human capital through succession planning.

PMID- 12526616
TI  - Developing a succession plan: the North Bronx Healthcare Network.
AB  - After 3 years of reorganizing a nursing department, surviving 2 very successful
      Joint Commission on Accreditation of Healthcare Organizations (JCAHO) visits,
      developing an outcomes-based leadership program for head nurses, and assisting a
      large health care network navigate change, a nurse executive stops to think about
      succession planning. The challenge to develop a plan includes her own history,
      others' definitions, and finally developing her own definition and plan. Included
      are the complications of planning within a network that includes long-term and
      loyal employees. Finally, the steps to achieving that plan are outlined with the
      goal of having the nursing department continue to flourish and survive in a
      diverse network system.

PMID- 12526617
TI  - Leadership development: the heart of succession planning.

PMID- 12526618
TI  - Preparing tomorrow's leaders through succession planning from the provider
      perspective.
AB  - "We never know.... Fate has a way of showing up at the most inopportune times. We
      had been planning for Ann's retirement for months. It was going to be a loss. Not
      only was she a long-term employee and strong manager, she could step in and lead
      anything. She would be sorely missed. We knew who was going to cover each of her
      areas of accountability. Sue would take one unit. John would manage the Dialysis
      Program. We had completed a job analysis, and everything was covered. We had
      already begun the shifting of accountabilities. September 2 was the big day. We
      had 3 months to go. Then the big opportunity came. We had been working on the
      merger for months before it finally happened. There was only one glitch. The
      culture shift was going to be huge. We needed someone to lead the process. Of
      course, who could do it better than Ann? She had been leading change for years.
      She was a master. She had the one skill for which we had no succession plan. We
      had one person that we could call, and within 3 months she would be gone. We had
      missed the mark. We had not completed our succession plan." These real-life
      stories show how critical succession planning can be to an organization. To do it
      well requires a clear vision of the strategic objectives of the organization,
      focused development programs, and continuous enrollment of both executives and
      employees within the organization. Leadership training, learning projects, and
      creating a coaching environment also are crucial elements of a successful
      succession plan.

PMID- 12526619
TI  - Managing succession planning: the Inova Health System.

PMID- 12526620
TI  - Defining generations in succession planning: there are four!
AB  - Never before have nursing leaders been faced with 4 generations of nurses working
      together, a turbulent health care system, and supply and demand issues.
      Succession planning with different generations requires a knowledge of their
      values and strengths. It means retaining and attracting new employees who can
      stabilize an organization.

PMID- 12526621
TI  - Relationship management: a key strategy for effective succession planning.

PMID- 12526622
TI  - Measuring leadership: measuring what counts for succession planning.
AB  - Organizations tend to favor measures of near-term, tangible achievement at the
      expense of long-term, intangible capacities such as leadership. Succession
      planning, which is intimately tied to measures of leadership competencies and
      leadership development, suffers as a result of this tendency. Effective planning
      requires senior managers to be willing to invest in the measurement needed to
      gauge where the organization stands with respect to future leadership
      requirements.

PMID- 12526623
TI  - Succession planning: lessons from the legal field.

PMID- 12526624
TI  - The case against mandatory overtime.

PMID- 12526625
TI  - A century of practice. Occupational health nursing. 1988.
AB  - Occupational health nursing has grown and developed throughout the last century,
      from the influence of a few nurses in the late 19th century to 1988. Today's
      occupational health nurses have a significant impact on millions of workers
      across the United States and worldwide in multinational corporations. Nurses
      currently enjoy expanded roles, including involvement in the political arena and
      policy-making decisions, development of health promotion programs, research, and
      education, as well as providing more traditional but equally important employee
      health services, counseling, and teaching. The American workforce, as well as
      management teams, have seen the outcomes of quality occupational health nursing
      care and contributions throughout the years. The practice of American
      occupational health nursing which began in very humble surroundings and
      conditions in the 19th century continues to thrive in the space age of the 1980s
      and 1990s and to plan for the challenges of the 21st century.

PMID- 12526626
TI  - Latent TB management--a clinical protocol update.

PMID- 12526627
TI  - Managing employee health problems--optimal use of independent medical
      evaluations.
AB  - The purpose of an IME is to obtain an impartial, objective evaluation of an
      employees health condition. Based on the evaluation, the examiner is asked to
      render an opinion to answer questions set forth in written communication to the
      examiner. The opinion, which is grounded in the examiners professional education,
      experience, and judgment, becomes a legal instrument. Occupational health nurses
      must be cognizant of the ramifications of an IME and the communications
      surrounding this examination. In addition, many factors can affect the quality of
      an IME. Occupational health nurses should be aware of these factors when
      facilitating an IME to ensure the precise focus and overall quality of the
      evaluation.

PMID- 12526628
TI  - Post offer screening.
AB  - A well designed post offer screening program including PDA, clear acceptable
      criteria, physical screening, standardized objective tests, and occupational and
      job specific tests can substantially decrease the number of injuries and
      resulting costs. The results of a study suggest post offer screening makes a
      difference on post hire injury and resulting costs. These findings are consistent
      with the literature reviewed. Occupational health professionals are key to the
      development, implementation, and evaluation of such a program and can directly
      affect the company's bottom line when employees are accurately matched to their
      job requirements.

PMID- 12526630
TI  - African American specialty educators.

PMID- 12526631
TI  - Native American/Indian specialty educators.

PMID- 12526632
TI  - Diabetes education for people with disabilities.
AB  - The AADE recognizes the special diabetes education and care needs of people with
      disabilities. The Americans with Disabilities Act requires that diabetes
      educators provide reasonable accommodations to people with disabilities in
      response to their particular individual needs. This position statement has been
      developed to provide guidance to diabetes educators regarding their ethical and
      legal responsibilities to people with disabilities, and to promote diabetes
      education for people with disabilities that is equal in quality to that received
      by people with no current disability.

PMID- 12526633
TI  - Cultural sensitivity: definition, application, and recommendations for diabetes
      educators.

PMID- 12526634
TI  - Evaluating a diabetes foot care program in a preceptorship for medical students.

PMID- 12526635
TI  - Counseling patients with type 2 diabetes and insulin resistance in the outpatient
      setting.
AB  - Insulin resistance is a major health concern. Besides being a leading risk factor
      for type 2 diabetes, it is also associated with hypertension, dyslipidemia,
      obesity, and cardiovascular disease. Making lifestyle changes can reduce insulin
      resistance and help prevent the onset of diabetes. For those with type 2
      diabetes, treatment with insulin-sensitizing drugs, such as the TZDs and
      biguanides, can improve glycemic control and prevent some of the adverse
      consequences of the disease. Adherence to both lifestyle and medication regimens
      is very important and should be actively supported by all members of the
      healthcare team. Diabetes educators, including pharmacists, can increase
      awareness of the underlying pathophysiology and clinical implications of insulin
      resistance. Diabetes educators also play a vital role in counseling patients with
      type 2 diabetes on strategies that reduce their risk of hyperglycemic
      complications and in providing support, education, and guidance. By understanding
      the disease and its management, diabetes educators can contribute to improved
      outcomes and help to reduce the impact of this worldwide epidemic.

PMID- 12526636
TI  - Developing and refining the research question: step 1 in the research process.

PMID- 12526637
TI  - White paper on the prevention of type 2 diabetes and the role of the diabetes
      educator.

PMID- 12526639
TI  - Perceived adherence to prescribed or recommended standards of care among adults
      with diabetes.
AB  - PURPOSE: Adults with diabetes were surveyed to determine the extent to which
      respondents perceived specific preventive regimens (diet, exercise, weight
      control, and education) had been prescribed or recommended, adhered to their
      prescribed regimens, and identified barriers to nonadherence. METHODS: Surveys
      were mailed to 2 samples of adults diagnosed with diabetes. The clinic sample was
      from health department clinics (n = 264); the agency sample was from a nonprofit
      agency serving people with diabetes (n = 111). RESULTS: Of the 4 preventive
      measures under investigation, diet plans and weight reduction were perceived as
      most commonly recommended by health professionals; exercise schedules were the
      least commonly recommended. Diabetes self-management education was reportedly
      recommended more often among the agency sample. In terms of adherence,
      approximately half of both samples were able to lose weight. A smaller portion of
      the clinic sample was able to get needed foods and exercise, and maintain weight
      loss. The most frequently cited reasons for nonadherence were cost,
      transportation, and other health conditions. CONCLUSIONS: Improvement in the
      implementation of preventive behaviors is needed, particularly exercise
      schedules. Barriers to care, such as costs and transportation, may need special
      consideration.

PMID- 12526638
TI  - Reliability and validity of a measure of perceived diabetes and dietary
      competence in African American women with type 2 diabetes.
AB  - PURPOSE: A general measure of perceived diabetes and dietary competence (PDDC)
      was developed to assess a person's sense of confidence and perceived behavioral
      control in diabetes and dietary self-management. Internal structure, reliability,
      and construct validity were evaluated. METHODS: There were 2 samples of African
      American women with type 2 diabetes; 226 patients in the development sample and
      225 patients in the validation sample. Factor analysis, Cronbach's coefficient
      alpha, and correlation analysis were used to assess reliability and validity of
      the PDDC measure. RESULTS: Three subscales were empirically determined by factor
      analysis: positive competence, negative dietary competence, and negative control.
      Cronbach's alphas for all subscales were good. Predicted relationships with
      measures of perceived health competence, self-efficacy, social support, and
      perceived dietary barriers were largely supported in construct validation.
      CONCLUSIONS: This study provides initial support for the internal reliability and
      validity of a perceived diabetes and dietary competence measure. Further research
      is needed to determine its validity in other samples of African Americans with
      type 2 diabetes and its clinical utility in evaluating diabetes self-management
      training.

PMID- 12526640
TI  - A focus group study of accessibility and related psychosocial issues in diabetes
      education for people with visual impairment.
AB  - PURPOSE: This study was conducted to identify accessibility and related
      psychosocial issues in diabetes care and education for visually impaired adults
      who have diabetes. METHODS: Two focus groups of adults with visual impairment and
      diabetes were conducted; data were recorded and analyzed. RESULTS: The 3 main
      issues identified were lack of access to up-to-date diabetes information in an
      accessible format, lack of understanding by healthcare providers of the needs and
      competencies of people with both visual impairment and diabetes, and lack of
      access to nonvisual diabetes self-management equipment. CONCLUSIONS: This study
      provides qualitative support for the view that visually impaired people in the
      United States may, as a group, be systematically excluded from receiving high
      quality diabetes care and education. Equal access to diabetes care and education
      for visually impaired people requires increased accessibility of diabetes care
      and education programs, and increased professional and public awareness that the
      diabetes programs are accessible. Some specific recommendations are to make all
      patient education materials available in low-vision/nonvisual formats and to
      teach all diabetes education professionals how to work effectively with visually
      impaired people.

PMID- 12526641
TI  - Quality improvement initiative to integrate teaching diabetes standards into home
      care visits.
AB  - PURPOSE: This quality improvement project was initiated to determine the quality
      of diabetes care for clients of a home health agency and to integrate the
      teaching of diabetes standards of care into home care nursing visits. METHODS: A
      descriptive study design was used to evaluate the effectiveness of teaching
      materials and the Standards of Care Teaching Program. Performance indicators and
      outcome measures from the American Diabetes Association Provider Recognition
      Program (ADA PRP) were used to determine the baseline status of diabetes care and
      for comparing performance measures from 50 home care clients. RESULTS: The
      educational materials and care plan interventions helped nurses learn the
      standards and facilitated tracking interventions and performance measures. These
      results showed statistical significance in performance measures for eye, foot,
      lipid tests, and diabetes self-management education, but not for hemoglobin A1C,
      urine protein, and medical nutrition therapy. CONCLUSIONS: The Standards of Care
      Teaching Program was a useful way to integrate the standards into a diabetes
      program and home care visits. Comparing clients' diabetes performance measures
      with national standards helped identify specific areas for quality improvement.

PMID- 12526642
TI  - The role of diabetes healthcare professionals in diabetes discrimination issues
      at work and school.

PMID- 12526643
TI  - Small-molecule switches for zinc finger transcription factors.
AB  - We have developed a general approach to generate selective small-molecule
      switches for zinc finger transcription factors based on the notion of structural
      complementation. A small molecule, 2-(4'-quinoline)benzimidazole (7), was
      identified by screening of a heterocycle library, which functionally rescues a
      structurally compromised transcription factor C7-F116A/H125G-VP16. Compound 7
      induces the activity of the mutant zinc finger in a luciferase-based
      transactivation assay by about 18-fold at 100 muM concentration. Surface plasmon
      resonance measurements revealed that compound 7 enhances the affinity between the
      mutant C7 and its cognate DNA sequence by 16-fold while a structurally analogous
      compound, 2-(2'-naphthyl)benzimidazole (8), showed no affinity enhancement,
      indicating there is a specific interaction between compound 7 and the mutant zinc
      finger. Taken together, these results suggest that the partial affinity recovery
      of the mutant transcription factor may be the mechanism for the functional rescue
      of the zinc finger transcription factor by compound 7.

PMID- 12526644
TI  - Correlated layer structures: a novel type of liquid crystalline phase with 2D
      lattice.
AB  - A novel liquid crystalline quaternary five-block molecule is reported which is
      composed of four incompatible molecular parts, a rigid biphenyl core, two polar
      2,3-dihydroxypropoxy groups in the terminal 4- and 4'-positions, and a branched
      semiperfluorinated chain in the lateral 3-position, consisting of a
      perfluorinated and a lipophilic hydrocarbon wing. The self-organization of this
      compound was studied by polarized light optical microscopy, differential scanning
      calorimetry, and X-ray diffraction of aligned samples. These investigations
      confirm a novel liquid crystalline phase with two-dimensional (2D) lattice
      (columnar mesophase), which results from the positional correlation of smectic
      layers. The layer structure results from the segregation of the bolaamphiphilic
      parts from the side chains. Within the aromatic sublayers the biphenyl cores are
      arranged parallel to the layer planes, and the hydrogen-bonding networks of the
      terminal diol groups are segregated from the biphenyl cores, forming separate
      columns. The correlation between adjacent layers is due to the (partial)
      segregation of the fluorinated and hydrogenated parts of the lateral chains in
      the nonpolar sublayers.

PMID- 12526645
TI  - An HIV reverse transcriptase-selective nucleoside chain terminator.
AB  - The synthesis of a 2',3'-dideoxynucleoside cytidine analogue, but one that lacks
      the O2-carbonyl, is described from 2-aminopyridine in an overall yield of 60%.
      The synthesis of the 2-pyridone C-nucleoside relies upon the use of a Heck-type
      coupling between an appropriately protected sugar glycal and the 5-iodo
      derivative of 2-aminopyridone. Upon conversion of the dideoxynucleoside to the
      corresponding 5'-triphosphate, the analogue ddNTP is observed to be a reasonable
      substrate with HIV reverse transcriptase (for a template dG residue), but is not
      a substrate for calf thymus DNA polymerase alpha or for human DNA polymerase
      beta. With the human mitochondrial DNA polymerase the analogue functions as a
      poor substrate. The observed polymerase selectivities appear to arise from the
      absence of the O2-carbonyl, which either results in a destabilized Watson-Crick
      base pair or represents a critical contact for some polymerases.

PMID- 12526646
TI  - Zeolite-coated mesostructured cellular silica foams.
AB  - ZSM-5- and NaY-coated MCF materials as new acid catalysts for conversion of bulky
      molecules were prepared by the coating procedure using diluted clear zeolite gel
      solutions. The resulting materials have high acidity and improved steam stability
      as compared to that of the corresponding MCF aluminosilica. This could be due to
      the zeolitic nature and relative hydrophobicity of the mesopore surface.

PMID- 12526647
TI  - Mapping photogenerated radicals in thin polymer films: fluorescence imaging using
      a prefluorescent radical probe.
AB  - Prefluorescent radical probes, in which fluorescence is activated by radical
      trapping, and photoinitiators were used to detect radical generation in polymer
      films using fluorescence spectroscopy and microscopy. Prefluorescent radical
      probes are the foundation of a fluorescence imaging system for polymer films,
      that may serve both as a mechanistic tool in the study of photoinitiated radical
      processes in polymer films and in the preparation of functional fluorescent
      images.

PMID- 12526648
TI  - Acetylcholine esterase-labeled CdS nanoparticles on electrodes:
      photoelectrochemical sensing of the enzyme inhibitors.
AB  - The photocurrents generated by a monolayer consisting of a CdS
      nanoparticles/acetylcholine esterase hybrid system associated with an electrode
      are controlled by the enzyme inhibitors.

PMID- 12526649
TI  - Model aluminum-poly(p-phenylenevinylene) interfaces studied by surface raman
      spectroscopy.
AB  - Polymeric organic light-emitting diodes (OLEDs) have emerged as inexpensive and
      versatile alternatives to traditional inorganic-based display technologies.
      Further advances in this field depend on extending device lifetimes and improving
      electroluminescence efficiencies, both of which are strongly coupled to the
      integrity of the electrode/organic contacts. Therefore, the deposition of low
      work function metals on organic materials has been extensively studied by X-ray
      photoelectron spectroscopy (XPS), ultraviolet photoemission spectroscopy (UPS),
      and near-edge X-ray adsorption fine structure (NEXAFS) to ascertain information
      about the chemical and electronic states within the interfacial region. However,
      to date, the only molecular structural information about metal-organic species
      formed in these regions has come from fits of theoretical models to existing XPS
      and UPS data. Very little direct structural information exists about the
      potential multitude of metal-organic species formed during cathode deposition. We
      report the use of surface Raman spectroscopy to study the interactions between
      aluminum and trans-stilbene, a model for poly(p-phenylenevinylene) (PPV). The
      Raman spectral data suggest preferential formation of covalent Al-C bonds at the
      vinylene carbons as opposed to the phenyl carbons of PPV.

PMID- 12526651
TI  - Carbonyl-ene reactions catalyzed by bis(oxazoline) copper (II) complexes proceed
      by a facile stepwise mechanism: DFT and ONIOM (DFT:PM3) studies.
AB  - The mechanism of a carbonyl-ene addition reaction catalyzed by a bis(oxazoline)
      copper (II) complex has been studied using DFT methods. We find that the reaction
      proceeds by a stepwise mechanism with very low barriers and have identified the
      role of the metal catalyst. We find that the more computationally economic ONIOM
      method gives accurate geometries for the stationary structures on the potential
      energy surface but that accurate energetics must be calculated at the full DFT
      level.

PMID- 12526650
TI  - Highly enantioenriched tetrahydropyridines from chiral organosilanes: application
      to the synthesis of quinolizidine alkaloid (-)-217A.
AB  - The tetrahydropyridine and piperidine subunits are widely found in biologically
      active molecules and natural products. Alhough considerable synthetic efforts
      have been made to reach these systems, there are few direct methods available for
      the preparation of enantionenriched tetrahydropyridines. A Lewis acid-promoted
      intramolecular imine crotylation is described and results in direct access to
      enantioenriched 2,6-cis- and 2,6-trans-3-trans-trisubstituted tetrahydropyridines
      with high diastereoselectivity. An example of the application of this methodology
      was demonstrated in an expedient total synthesis of (-)-quinolizidine 217A. The
      absolute stereochemistry of this natural product was established by the total
      synthesis.

PMID- 12526652
TI  - Patterned langmuir-blodgett films of monodisperse nanoparticles of iron oxide
      using soft lithography.
AB  - Langmuir-Blodgett (LB) films of monodisperse iron oxide nanoparticles have been
      successfully deposited onto patterned poly(dimethylsiloxane) surfaces. These
      patterned LB films of iron oxide nanoparticles were transferred onto solid
      substrates using micro contact printing.

PMID- 12526653
TI  - On the stability of a single-turn alpha-helix: the single versus
      multiconformation problem.
AB  - The pentapeptide Ac-HAAAH-NH2, cyclized through its imidazoles by PdII to give
      [Pd(en)(peptide)]2+, has recently been evaluated by 2-D NMR and simulated
      annealing as a single alpha-helix conformation in solution. In the present work,
      we have questioned this assumption by developing Pd2+ parameters for AMBER*,
      performing an extensive conformational search for the [Pd(en)(peptide)]2+, and
      deconvoluting the averaged NMR data into eight rapidly equilibrating
      conformations with populations ranging from 2 to 55%. None of the latter
      correspond to the alpha-helix, although a 3% form possesses a related structure.
      As a critical component of interpreting an averaged NMR spectrum in terms of a
      single conformation, we advise testing this assumption with a method that permits
      conformational deconvolution.

PMID- 12526654
TI  - Tuning copper-dioxygen reactivity and exogenous substrate oxidations via
      alterations in ligand electronics.
AB  - Copper(I)-dioxygen adducts are important in biological and industrial processes.
      For the first time we explore the relationship between ligand electronics, CuI-O2
      adduct formation and exogenous substrate reactivity. The copper(I) complexes
      [CuI(R-MePY2)]+ (1R, where R = Cl, H, MeO, Me2N) were prepared; where R-MePY2 are
      4-pyridyl substituted bis[2-(2-pyridyl)ethyl]methylamine chelates. Both the redox
      potential of 1R (ranging from E1/2 = -270 mV for 1Cl to -440 mV for 1MeN vs
      FeCp2/FeCp2+) and nuCO of the CO adducts of 1R (ranging from 2093 cm-1 for 1Cl-CO
      to 2075 cm-1 for 1Me2N-CO) display modest but expected systematic shifts.
      Dioxygen readily reacts with 1H, 1MeO, and 1Me2N, forming the side-on peroxo
      CuII2 complexes [{CuII(R-MePY2)}2(O2)]2+ (2R, also containing some bis-mu-oxo
      CuIII2 isomer), but there is no reaction with 1Cl. Stopped-flow studies in
      dichloromethane show that the formation of 2Me2N from dioxygen and 1Me2N proceeds
      with a k = 8.2(6) x 104 M-2 s-1 (183 K, DeltaH = -20.3(6) kJ mol-1, DeltaS = 
      219(3) J mol-1 K-1). Solutions of 2R readily oxidize exogenous substrates (9,10
      dihydroanthracene --> anthracene, tetrahydrofuran (THF) --> 2
      hydroxytetrahydrofuran (THF-OH), N,N-dimethylaniline --> N-methylaniline and
      formaldehyde, benzyl alcohol --> benzaldehyde, benzhydrol --> benzophenone, and
      methanol --> formaldehyde), forming the bis-mu-hydroxo-CuII2 complexes [{CuII(R
      MePY2)(OH)}2]2+ (3R). Product yields increase as the R-group is made more
      electron-donating, and in some cases are quantitative with 2Me2N. Pseudo-first
      order rate constants for THF and methanol oxidation reactions demonstrate a
      remarkable R-group dependence, again favoring the strongest ligand donor (i.e., R
      = Me2N). For THF oxidation to THF-OH a nearly 1500-fold increase in reaction rate
      is observed (kobs = 2(1) x 10-5 s-1 for 2H to 3(1) x 10-2 s-1 for 2Me2N), while
      methanol oxidation to formaldehyde exhibits an approximately 2000-fold increase
      (kobs = 5(1) x 10-5 s-1 for 2H to 1(1) x 10-1 s-1 for 2Me2N).

PMID- 12526655
TI  - High-efficiency red-light emission from polyfluorenes grafted with cyclometalated
      iridium complexes and charge transport moiety.
AB  - We report a new route for the design of electroluminescent polymers by grafting
      high-efficiency phosphorescent organometallic complexes as dopants and charge
      transport moieties onto alky side chains of fully conjugated polymers for polymer
      light-emitting diodes (PLED) with single layer/single polymers. The polymer
      system studied involves polyfluorene (PF) as the base conjugated polymer,
      carbazole (Cz) as the charge transport moiety and a source for green emission by
      forming an electroplex with the PF main chain, and cyclometalated iridium (Ir)
      complexes as the phosphorescent dopant. Energy transfer from the green Ir complex
      or an electroplex formed between the fluorene main chain and side-chain carbazole
      moieties, in addition to that from the PF main chain, to the red Ir complex can
      significantly enhance the device performance, and a red light-emitting device
      with the high efficiency 2.8 cd/A at 7 V and 65 cd/m2, comparable to that of the
      same Ir complex-based OLED, and a broad-band light-emitting device containing
      blue, green, and red peaks (2.16 cd/A at 9 V) are obtained.

PMID- 12526656
TI  - Double cyclization via intramolecular coupling between cyclohexadiene-Fe(CO)3
      complexes and pendant conjugated dienes.
AB  - Intramolecular double cyclization between a cyclohexadiene-Fe(CO)3 complex and a
      pendant diene yielded a tricyclic molecule containing a spirocenter, with defined
      relative stereochemistry of four contiguous carbon centers. The nature of the
      substituent on the pendant diene moiety has a significant effect on the yield: an
      ester group leads to lower yield. The product has a conjugated cyclohexadiene or
      methoxycyclohexadiene system; the latter was converted to an enone.

PMID- 12526657
TI  - Conformationally homogeneous cyclic tetrapeptides: useful new three-dimensional
      scaffolds.
AB  - The most commonly recognized motifs in protein-protein interactions are gamma and
      beta turns, which are defined by three to four contiguous amino acids in a
      peptide sequence. Cyclic tetrapeptides thus represent minimalist turn mimetics,
      but their usefulness is compromised by strain in their 12-membered rings, making
      them difficult to cyclize, unstable to hydrolysis/metabolism, and
      conformationally heterogeneous in polar solvents. Appropriate placement of a beta
      amino acid in a tetrapeptide creates a 13-membered ring that is shown to be
      easier to cyclize, hydrolytically more stable, and conformationally homogeneous
      in polar solvents such as DMSO and water. Three-dimensional structures reveal
      that these cyclic tetrapeptides are novel rigid scaffolds, their unique side
      chain projections matching a structurally diverse range of useful nonpeptidic
      templates, including sugars and spirocyclic compounds, found as components of
      natural products. The results provide a potentially useful link between protein
      architecture and organic natural products. On the basis of protein turn sequences
      (not protein structures) alone simple cyclic tetrapeptide libraries with a beta
      amino acid can be rationally designed as conformationally restricted, easily
      synthesized, and stereochemically controlled screening tools for rapidly
      identifying pharmacophore space that can then be computer-matched to more complex
      known natural product templates for drug development.

PMID- 12526658
TI  - Are J(Si-H) NMR coupling constants really a probe for the existence of
      nonclassical H-Si interactions?
AB  - A series of hydridosilyl complexes of tantalum, Cp(ArN)Ta(PMe3)(H)(SiClnR3-n) (n
      = 0-3), was prepared and studied by 29Si NMR, X-ray diffraction, and DFT
      calculations. An unprecedented increase of the J(Si-H) coupling constant between
      the hydride and silyl ligands from 14 Hz for n = 0 to 50 Hz n = 3 was observed,
      which however, according to DFT calculations, does not correspond to stronger
      bonding interaction between silicon and hydride ligands, with the strongest
      interaction being for n = 1.

PMID- 12526659
TI  - Dynamic effects on j-couplings across hydrogen bonds in proteins.
AB  - We combine molecular dynamics simulation (MD) with density functional theory
      (DFT)/finite perturbation theory (FPT) to obtain the Fermi contact contributions
      to the 3hJNC' couplings in the SMN Tudor domain. Our results show that the effect
      of conformational motion needs to be considered for the accurate prediction of
      these scalar couplings. For hydrogen bonds in the beta-sheet regions, the
      calculated cumulative J-coupling averages remain constant after the first 200 ps.
      In the more flexible regions at the edges of the beta-sheets, the cumulative J
      coupling averages vary over the 500-ps trajectory, providing a qualitative
      insight into the degree of conformational motion in different regions of the
      protein.

PMID- 12526660
TI  - A novel modified baylis-hillman reaction of propiolate.
AB  - A new reaction of propiolates and aldehydes mediated by DABCO analogous to the
      Baylis-Hillman reaction is described. This reaction provided novel beta
      functionalized Baylis-Hillman products and a new methodology for the generation
      of alkylidene carbene species.

PMID- 12526661
TI  - Palladium-catalyzed intramolecular oxidative alkylation of unactivated olefins.
AB  - Reaction of 5,5-dimethyl-8-nonene-2,4-dione catalyzed by PdCl2(CH3CN)2 (5 mol %)
      in the presence of CuCl2 (2.5 equiv) at room temperature for 3 h formed 2-acetyl
      3,6,6-trimethyl-2-cyclohexenone in 96% isolated yield. Palladium-catalyzed
      intramolecular oxidative alkylation tolerated a range of substitution and was
      applicable to the synthesis of spirobicyclic compounds and to the cyclization of
      zeta-alkenyl beta-keto esters.

PMID- 12526662
TI  - Resorcinarenes as templates: a general strategy for the synthesis of large
      macrocycles.
AB  - The concept that resorcinarenes can be used as templates for the synthesis of
      large macrocycles is introduced. By way of example, previously inaccessible,
      aromatic crown ethers compounds are synthesized.

PMID- 12526663
TI  - Evidence for vesicle formation during the synthesis of catanionic templated
      mesoscopically ordered silica as studied by Cryo-TEM.
AB  - The formation of vesicles during the synthesis of mesostructured surfactant
      silicate materials has been evidenced for the first time by applying in situ Cryo
      TEM. A mixture of anionic and cationic surfactants was used to fine-tune the
      packing parameter of the supramolecular surfactant assembly. It is shown that the
      vesicles are formed during the course of the reaction and suggested to be a
      consequence of silicate condensation reactions. Furthermore, the study confirms
      earlier suggestions that the silicate-surfactant micelles are capable of
      solubilizing hydrophobic additives during the early stages of the reaction.

PMID- 12526665
TI  - Induction of a remarkable conformational change in a human telomeric sequence by
      the binding of naphthyridine dimer: inhibition of the elongation of a telomeric
      repeat by telomerase.
AB  - The binding of a dimeric form of the 2-amino-1,8-naphthyridine derivative
      (naphthyridine dimer) to a human telomeric sequence, TTAGGG, was investigated by
      UV melting, CD spectra, and CSI-MS measurements. Both the 9-mer d(TTAGGGTTA) and
      the 15-mer d(TTAGGGTTAGGGTTA) showed apparent melting temperatures (T(m)) of 45.6
      and 63.6 degrees C, respectively, in the presence of naphthyridine dimer (30
      microM) in sodium cacodylate buffer (50 mM, pH 7.0) containing 100 mM NaCl. The
      CD spectra at 235 and 255 nm of the 9-mer increased in intensity accompanied with
      strong induced CDs at 285 and 340 nm upon complex formation with naphthyridine
      dimer. UV titration of the binding of naphthyridine dimer to the 9-mer at 320 nm
      showed a hypochromism of the spectra. A Scatchard plot of the data showed the
      presence of multiple binding sites with different association constants. Cold
      spray ionization mass spectrometry of the complex between naphthyridine dimer and
      the 9-mer clearly showed that one to three molecules of the ligand bound to the
      dimer duplex of the 9-mer. Telomeric repeat elongation assay showed that the
      binding of naphthyridine dimer to the telomeric sequence inhibits the elongation
      of the sequence by telomerase.

PMID- 12526664
TI  - Efficient RNase H-directed cleavage of RNA promoted by antisense DNA or 2'F-ANA
      constructs containing acyclic nucleotide inserts.
AB  - The ability of modified antisense oligonucleotides (AONs) containing acyclic
      interresidue units to support RNase H-promoted cleavage of complementary RNA is
      described. Manipulation of the backbone and sugar geometries in these
      conformationally labile monomers shows great benefits in the enzymatic
      recognition of the nucleic acid hybrids, while highlighting the importance of
      local strand conformation on the hydrolytic efficiency of the enzyme more
      conclusively. Our results demonstrate that the duplexes support remarkably high
      levels of enzymatic degradation when treated with human RNase HII, making them
      efficient mimics of the native substrates. Furthermore, interesting linker
      dependent modulation of enzymatic activity is observed during in vitro assays,
      suggesting a potential role for this AON class in an RNase H-dependent pathway of
      controlling RNA expression. Additionally, the butyl-modified 2'F-ANA AONs
      described in this work constitute the first examples of a nucleic acid species
      capable of eliciting high RNase H activity while possessing a highly flexible
      molecular architecture at predetermined sites along the AON.

PMID- 12526666
TI  - Specific control of peptide assembly with combined hydrophilic and hydrophobic
      interfaces.
AB  - Designed coiled-coil heterotrimers are described whose assembly is governed by
      both hydrophobic and hydrophilic forces. Sterically matched hydrophobic core side
      chain packing of alanine and cyclohexylalanine has been shown to promote
      formation of a 1:1:1 heterotrimer. Manipulation of hydrophilic glutamic acid
      (Glu)/lysine (Lys) pairs at each of three helical contact interfaces provides a
      secondary recognition mechanism. Peptides with matched cores and hydrophilic
      contacts form stable heterotrimers (DeltaG(unf) at 25 degrees C = 17.93 kcal/mol;
      MW(app) = 11362 vs 11563 calcd for trimer), as do those with a single Lys/Lys
      (but not Glu/Glu) interface. The additional specificity engendered by
      simultaneous operation of two interfaces was used to design a system in which six
      different peptides are mixed to form three specific and independent heterotrimers
      in the same solution.

PMID- 12526667
TI  - Insights into the acylation mechanism of class A beta-lactamases from molecular
      dynamics simulations of the TEM-1 enzyme complexed with benzylpenicillin.
AB  - Herein, we present results from molecular dynamics MD simulations ( approximately
      1 ns) of the TEM-1 beta-lactamase in aqueous solution. Both the free form of the
      enzyme and its complex with benzylpenicillin were studied. During the simulation
      of the free enzyme, the conformation of the Omega loop and the interresidue
      contacts defining the complex H-bond network in the active site were quite
      stable. Most interestingly, the water molecule connecting Glu166 and Ser70 does
      not exchange with bulk solvent, emphasizing its structural and catalytic
      relevance. In the presence of the substrate, Ser130, Ser235, and Arg244 directly
      interact with the beta-lactam carboxylate via H-bonds, whereas the Lys234
      ammonium group has only an electrostatic influence. These interactions together
      with other specific contacts result in a very short distance ( approximately 3 A)
      between the attacking hydroxyl group of Ser70 and the beta-lactam ring carbonyl
      group, which is a favorable orientation for nucleophilic attack. Our simulations
      also gave insight into the possible pathways for proton abstraction from the
      Ser70 hydroxyl group. We propose that either the Glu166 carboxylate-Wat1 or the
      substrate carboxylate-Ser130 moieties could abstract a proton from the
      nucleophilic Ser70.

PMID- 12526668
TI  - Nanomolar inhibitors of AmpC beta-lactamase.
AB  - beta-lactamases are the most widespread resistance mechanism to beta-lactam
      antibiotics, such as the penicillins and the cephalosporins. In an effort to
      combat these enzymes, a combination of stereoselective organic synthesis,
      enzymology, microbiology, and X-ray crystallography was used to design and
      evaluate new carboxyphenyl-glycylboronic acid transition-state analogue
      inhibitors of the class C beta-lactamase AmpC. The new compounds improve
      inhibition by over 2 orders of magnitude compared to analogous glycylboronic
      acids, with K(i) values as low as 1 nM. On the basis of the differential binding
      of different analogues, the introduced carboxylate alone contributes about 2.1
      kcal/mol in affinity. This carboxylate corresponds to the ubiquitous C3(4)'
      carboxylate of beta-lactams, and this energy represents the first thermodynamic
      measurement of the importance of this group in molecular recognition by class C
      beta-lactamases. The structures of AmpC in complex with two of these inhibitors
      were determined by X-ray crystallography at 1.72 and 1.83 A resolution. These
      structures suggest a structural basis for the high affinity of the new compounds
      and provide templates for further design. The highest affinity inhibitor was 5
      orders of magnitude more selective for AmpC than for characteristic serine
      proteases, such as chymotrypsin. This inhibitor reversed the resistance of
      clinical pathogens to the third generation cephalosporin ceftazidime; it may
      serve as a lead compound for drug discovery to combat bacterial resistance to
      beta-lactam antibiotics.

PMID- 12526669
TI  - Antibody recognition of chiral surfaces. Enantiomorphous crystals of leucine
      leucine-tyrosine.
AB  - Monoclonal antibodies were selected after immunization with crystals of the
      tripeptide l-leucine-l-leucine-l-tyrosine. They interact with the tripeptide
      crystals, but do not interact with the tripeptide molecule, with other
      crystalline surfaces, or with adsorbed protein. The interactions of two
      antibodies with crystals of l-Leu-l-Leu-l-Tyr and of its enantiomer d-Leu-d-Leu-d
      Tyr were characterized in depth. Antibody 48E is stereoselective and
      enantioselective: it recognizes only the [011] faces of the l-Leu-l-Leu-l-Tyr
      crystals, and not the enantiomorphous [011] faces of d-Leu-d-Leu-d-Tyr crystals,
      or any other faces of either crystal. In contrast, antibody 602E is poorly
      stereoselective and is not enantioselective: it recognizes the crystals of both
      enantiomers, interacting with a number of different faces of each. The different
      recognition patterns are explained on the basis of the nature of the interactions
      and the structure of the interacting surfaces. Understanding this antibody
      specificity advances our general understanding of surface recognition and
      transfer of chiral information across biological interfaces.

PMID- 12526670
TI  - Molecular recognition in (+)-alpha-pinene oxidation by cytochrome P450cam.
AB  - Oxygenated derivatives of the monoterpene (+)-alpha-pinene are found in plant
      essential oils and used as fragrances and flavorings. (+)-alpha-Pinene is
      structurally related to (+)-camphor, the natural substrate of the heme
      monooxygenase cytochrome P450(cam) from Pseudomonas putida. The aim of the
      present work was to apply the current understanding of P450 substrate binding and
      catalysis to engineer P450(cam) for the selective oxidation of (+)-alpha-pinene.
      Consideration of the structures of (+)-camphor and (+)-alpha-pinene lead to
      active-site mutants containing combinations of the Y96F, F87A, F87L, F87W, and
      V247L mutations. All mutants showed greatly enhanced binding and rate of
      oxidation of (+)-alpha-pinene. Some mutants had tighter (+)-alpha-pinene binding
      than camphor binding by the wild-type. The most active was the Y96F/V247L mutant,
      with a (+)-alpha-pinene oxidation rate of 270 nmol (nmol of P450(cam))(-)(1) min(
      )(1), which was 70% of the rate of camphor oxidation by wild-type P450(cam).
      Camphor is oxidized by wild-type P450(cam) exclusively to 5-exo-hydroxycamphor.
      If the gem dimethyl groups of (+)-alpha-pinene occupied similar positions to
      those found for camphor in the wild-type structure, (+)-cis-verbenol would be the
      dominant product. All P450(cam) enzymes studied gave (+)-cis-verbenol as the
      major product but with much reduced selectivity compared to camphor oxidation by
      the wild-type. (+)-Verbenone, (+)-myrtenol, and the (+)-alpha-pinene epoxides
      were among the minor products. The crystal structure of the Y96F/F87W/V247L
      mutant, the most selective of the P450(cam) mutants initially examined, was
      determined to provide further insight into P450(cam) substrate binding and
      catalysis. (+)-alpha-Pinene was bound in two orientations which were related by
      rotation of the molecule. One orientation was similar to that of camphor in the
      wild-type enzyme while the other was significantly different. Analysis of the
      enzyme/substrate contacts suggested rationalizations of the product distribution.
      In particular competition rather than cooperativity between the F87W and V247L
      mutations and substrate movement during catalysis were proposed to be major
      factors. The crystal structure lead to the introduction of the L244A mutation to
      increase the selectivity of pinene oxidation by further biasing the binding
      orientation toward that of camphor in the wild-type structure. The
      F87W/Y96F/L244A mutant gave 86% (+)-cis-verbenol and 5% (+)-verbenone. The
      Y96F/L244A/V247L mutant gave 55% (+)-cis-verbenol but interestingly also 32% (+)
      verbenone, suggesting that it may be possible to engineer a P450(cam) mutant that
      could oxidize (+)-alpha-pinene directly to (+)-verbenone. Verbenol, verbenone,
      and myrtenol are naturally occurring plant fragrance and flavorings. The
      preparation of these compounds by selective enzymatic oxidation of (+)-alpha
      pinene, which is readily available in large quantities, could have applications
      in synthesis. The results also show that the protein engineering of P450(cam) for
      high selectivity of substrate oxidation is more difficult than achieving high
      substrate turnover rates because of the subtle and dynamic nature of enzyme
      substrate interactions.

PMID- 12526671
TI  - A modular approach toward functionalized three-dimensional macromolecules: from
      synthetic concepts to practical applications.
AB  - A new strategy for the preparation of functional, multiarm star polymers via
      nitroxide-mediated "living" radical polymerization has been explored. The
      generality of this approach to the synthesis of three-dimensional macromolecular
      architectures allows for the construction of nanoscopically defined materials
      from a wide range of different homo, block, and random copolymers combining both
      apolar and polar vinylic repeat units. Functional groups can also be included
      along the backbone or as peripheral/chain end groups, thereby modulating the
      reactivity and polarity of defined portions of the stars. This modular approach
      to the synthesis of three-dimensional macromolecules permits the application of
      these tailored materials as multifunctional hosts for hydrogen bonding,
      nanoparticle formation, and as scaffolds for catalytic groups. Examples of
      applications of the functional stars in catalysis include their use in a Heck
      type coupling as well as an enantioselective addition reaction.

PMID- 12526672
TI  - A new model for simulating 3-d crystal growth and its application to the study of
      antifreeze proteins.
AB  - A novel computational technique for modeling crystal formation has been developed
      that combines three-dimensional (3-D) molecular representation and detailed
      energetics calculations of molecular mechanics techniques with the less
      sophisticated probabilistic approach used by statistical techniques to study
      systems containing millions of molecules undergoing billions of interactions.
      Because our model incorporates both the structure of and the interaction energies
      between participating molecules, it enables the 3-D shape and surface properties
      of these molecules to directly affect crystal formation. This increase in model
      complexity has been achieved while simultaneously increasing the number of
      molecules in simulations by several orders of magnitude over previous statistical
      models. We have applied this technique to study the inhibitory effects of
      antifreeze proteins (AFPs) on ice-crystal formation. Modeling involving both fish
      and insect AFPs has produced results consistent with experimental observations,
      including the replication of ice-etching patterns, ice-growth inhibition, and
      specific AFP-induced ice morphologies. Our work suggests that the degree of AFP
      activity results more from AFP ice-binding orientation than from AFP ice-binding
      strength. This technique could readily be adapted to study other crystal and
      crystal inhibitor systems, or to study other noncrystal systems that exhibit
      regularity in the structuring of their component molecules, such as those
      associated with the new nanotechnologies.

PMID- 12526673
TI  - Paramagnetic defect centers at the MgO surface. An alternative model to oxygen
      vacancies.
AB  - On the basis of embedded cluster calculations, we propose a new model for the
      structure of paramagnetic color centers at the MgO surface usually denoted as
      F(S)(H)(+) (an electron trapped near an adsorbed proton). These centers are
      produced by exposing the surface of polycrystalline MgO to H(2) followed by UV
      irradiation. We demonstrate that properties of H atom absorbed at surface sites
      such as step edges (MgO(step)) and reverse corner sites (MgO(RC)), formed at the
      intersection of two step edges, are compatible with a number of features observed
      for F(S)(H)(+). Our calculations suggest that (i) H(2) dissociates at the reverse
      corner site heterolytically and that there is no barrier for this exothermic
      reaction; (ii) the calculated vibrations of the resulting MgO(RC)(H(+))(H(-))
      complex are fully consistent with the measured ones; (iii) desorption of a
      neutral H atom from the diamagnetic precursor requires UV light and leads to the
      formation of stable neutral paramagnetic centers at the surface,
      MgO(step)(H(+))(e(-))(trapped) and MgO(RC)(H(+))(e(-))(trapped). The computed
      isotropic hyperfine coupling constants and optical transitions of these centers
      are in broad agreement with the existing experimental data. We argue that these
      centers, which do not belong to the class of "oxygen vacancies", are two of the
      many possible forms of the F(S)(H)(+) defect center.

PMID- 12526674
TI  - Activation of 3-amino-1,2,4-benzotriazine 1,4-dioxide antitumor agents to
      oxidizing species following their one-electron reduction.
AB  - The mechanism by which a benzotriazine 1,4-dioxide class of anticancer drugs
      produce oxidizing radicals following their one-electron reduction has been
      investigated using tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide, 1) and
      its 6-methoxy (6), 7-dimethylamino (7), and 8-methyl (8) analogues. By measuring
      the changes in absorption with pH, we found that the radical anions undergo
      protonation with radical pK(r) values of 6.19 +/- 0.05, 6.10 +/- 0.03, 6.45 +/-
      0.04, and 6.60 +/- 0.04, respectively. The one-electron reduced species underwent
      a first-order reaction, with increased rate constants from 112 +/- 23 s(-)(1) for
      1 to 777 +/- 12 s(-)(1)(6), 1120 +/- 29 s(-)(1) (7), and 825 +/- 89 s(-)(1) (8)
      at pH 7. No overall change in conductance was observed following the one-electron
      reduction of 6, and 8 at pH 4.5, consistent with the protonation of the radical
      anions, but a loss in conductance was seen for one-electron reduced 7 because of
      further protonation of the initially formed radical. This is assigned to the
      protonation of the dimethylamino group of the radical species, which has a pK(a)
      of 8.8 +/- 0.3. All conductance changes take place on a time-scale shorter than
      those of the above first-order reactions, which are not associated with the
      formation or loss of charged species. The absorption spectra present at the end
      of the unimolecular reactions were found to be similar to those formed
      immediately upon the one-electron oxidation of the respective substituted 3-amino
      1,2,4-benzotriazine 1-oxides, and it is suggested that common benzotriazinyl
      radicals are formed by both routes. All these intermediate radicals underwent
      dismutation to produce final spectra matched by equal contributions of the parent
      compound and their respective substituted 3-amino-1,2,4-benzotriazine 1-oxides.
      By establishing redox equilibria between the intermediate radicals formed on the
      one-electron oxidation of the respective 3-amino-1,2,4-benzotriazine 1-oxides of
      the compounds and reference compounds, we found the one-electron reduction
      potential of the oxidizing radicals to range from 0.94 to 1.31 V. The
      benzotriazinyl radical of tirapazamine was found to oxidize dGMP and 2
      deoxyribose with rate constants of (1.4 +/- 0.2) x 10(8) M(-)(1) s(-)(1) and (3.7
      +/- 0.5) x 10(6) M(-)(1) s(-)(1), respectively.

PMID- 12526675
TI  - Sugar-based gemini surfactant with a vesicle-to-micelle transition at acidic pH
      and a reversible vesicle flocculation near neutral pH.
AB  - A sugar-based (reduced glucose) gemini surfactant forms vesicles in dilute
      aqueous solution near neutral pH. At lower pH, there is a vesicle-to-micelle
      transition within a narrow pH region (pH 6.0-5.6). The vesicles are transformed
      into large cylindrical micelles that in turn are transformed into small globular
      micelles at even lower pH. In the vesicular pH region, the vesicles are
      positively charged at pH < 7 and exhibit a good colloidal stability. However,
      close to pH 7, the vesicles become unstable and rapidly flocculate and eventually
      sediment out from the solution. We find that the flocculation correlates with low
      vesicle zeta-potentials and the behavior is thus well predicted by the classical
      DLVO theory of colloidal stability. Surprisingly, we find that the vesicles are
      easily redispersed by increasing the pH to above pH 7.5. We show that this is due
      to a vesicle surface charge reversal resulting in negatively charged vesicles at
      pH > 7.1. Adsorption, or binding, of hydroxide ions to the vesicular surface is
      likely the cause for the charge reversal, and a hydroxide ion binding constant is
      calculated using a Poisson-Boltzmann model.

PMID- 12526676
TI  - Dimethylzinc-mediated additions of alkenylzirconocenes to aldimines. New
      methodologies for allylic amine and C-cyclopropylalkylamine syntheses.
AB  - Hydrozirconation of alkynes with zirconocene hydrochloride followed by in situ
      transmetalation to dimethylzinc provides access to reactive alkenyl
      organometallic reagents from readily available precursors. Upon addition of
      imines, 1,2-attack leads to synthetically useful allylic amine building blocks.
      In the presence of CH(2)I(2) or CH(2)Cl(2), the N-metalated allylic amide
      intermediate is cyclopropanated and C-cyclopropylalkylamines are formed in high
      yield and excellent diastereoselectivities favoring the anti products. The use of
      enynes as starting materials for this domino reaction provides conjugated
      biscyclopropanes and thus allows the stereoselective formation of five new carbon
      carbon bonds. A transition state that explains the need for both zirconocene
      complex and alkyl zinc in the cyclopropanation reaction is proposed.

PMID- 12526677
TI  - Secondary hypervalent I(III)...O interactions: synthesis and structure of
      hypervalent complexes of diphenyl-lambda3-iodanes with 18-crown-6.
AB  - Reported here for the first time are the synthesis and characterization of
      supramolecular complexes between diaryl-lambda(3)-iodanes and 18-crown-6 (18C6).
      Slow evaporation of solvents afforded 1:1 and 2:1 complexes between Ph(2)IBF(4)
      and 18C6 as stable crystals, depending on the conditions. X-ray crystal
      structures of these complexes indicated that each iodine atom contacts with the
      three adjacent oxygen atoms of 18C6 through two hypervalent secondary bonding and
      a weak interaction. (1)H NMR analyses and CSI-MS spectra showed that, in
      dichloromethane solution, Ph(2)IBF(4) exclusively forms the 1:1 complex with 18C6
      (binding constant K(a), 1.02 x 10(3) M(-)(1)). The binding constants decrease
      with the increased solvent donor ability (Gutmann's DN). Changing the heteroatom
      ligand from BF(4) to the less nucleophilic PF(6) and AsF(6) increased the binding
      constant by about six times. Substitution of an electron-withdrawing group onto
      the para position of Ph(2)IBF(4) tends to increase in the complex stability. A
      linear Hammett relationship (rho = 0.59) between log K(a) and sigma(p)(+) values
      of substituents indicates that the diaryl-lambda(3)-iodanes with electropositive
      iodine(III) interact more efficiently with 18C6. Decreased binding magnitude was
      measured with 15C5, dibenzo-18C6, dibenzo-21C7, and dibenzo-30C10.

PMID- 12526678
TI  - Characterization of chromodulin by X-ray absorption and electron paramagnetic
      resonance spectroscopies and magnetic susceptibility measurements.
AB  - The biologically active form of the essential trace element chromium is believed
      to be the oligopeptide chromodulin. Chromodulin binds four chromic ions before
      binding at or near the active site of activating insulin receptor and
      subsequently potentiating the tyrosine kinase activity of the receptor. Charge
      balance arguments and preliminary spectroscopic studies suggested that the
      chromic centers might be part of a multinuclear assembly. Using a combination of
      X-ray absorption and electron paramagnetic resonance spectroscopies and variable
      temperature magnetic susceptibility measurements, we found that holochromodulin
      is shown to possess an antiferromagnetically coupled trinuclear assembly which
      probably weakly interacts with a fourth chromium center. The chromium centers
      possess octahedron coordination comprised of oxygen-based ligation, presumably
      derived primarily from oligopeptide-supplied carboxylate groups. X-ray absorption
      data cannot be reproduced with the presence of sulfur atom(s), indicating that
      the cysteine thiolate group does not coordinate to the chromium centers. Thus,
      chromodulin possesses a unique type of multinuclear assembly, distinct from those
      known in other bioinorganic systems.

PMID- 12526679
TI  - Palladium(II) complex as a sequence-specific peptidase: hydrolytic cleavage under
      mild conditions of X-Pro peptide bonds in X-Pro-Met and X-Pro-His segments.
AB  - The X-Pro peptide bond (in which X represents any amino acid residue) in peptides
      and proteins is resistant to cleavage by most proteolytic enzymes. We show that
      [Pd(H(2)O)(4)](2+) ion can selectively hydrolyze this tertiary peptide bond
      within the X-Pro-Met and X-Pro-His sequence segments. The hydrolysis requires an
      equimolar amount of the Pd(II) reagent and occurs under mild conditions-at
      temperature as low as 20 degrees C (with half-life of 1.0 h at pH 2.0) and at pH
      as high as 7.0 (with half-life of 4.2 h at pH 7.0 and 40 degrees C). The
      secondary peptide bond, exemplified by X-Gly in the X-Gly-Met and X-Gly-His
      sequence segments, however, is cleaved only in weakly acidic solution (pH < 4.0)
      and more slowly (half-life is 4.2 h at pH 2.0 and 60 degrees C). We explain the
      sequence-specificity of X-Pro cleavage by NMR spectroscopic analysis of the
      coordination of the X-Pro-Met segment to the Pd(II) ion. We give indirect
      evidence for the mechanism of cleavage by analyzing the conformation of the
      scissile X-Pro peptide bond, and by comparing the rate constants for the cleavage
      of the tertiary X-Pro peptide bond, the tertiary X-Sar peptide bond (Sar is N
      methyl glycine), and the typical secondary X-Gly peptide bond in a set of
      analogous oligopeptides. Methionine and histidine side chains provide the
      recognition by selectively binding (anchoring) the Pd(II) ion. The proline
      residue provides the enhanced activity because its tertiary X-Pro peptide bond
      favors the cleavage-enhancing binding of the Pd(II) ion to the peptide oxygen
      atom and prevents the cleavage-inhibiting binding of the Pd(II) ion upstream of
      the anchoring (histidine or methionine) residue. Cleavage can be switched from
      the residue-selective to the sequence-specific mode by simply adjusting the pH of
      the aqueous solution. In acidic solutions, any X-Y bond in X-Y-Met and X-Y-His
      segments is cleaved because the cleavage is directed by anchoring methionine and
      histidine residues. In mildly acidic and neutral solutions, only the X-Pro bond
      in X-Pro-Met and X-Pro-His sequences is cleaved because of an interplay between
      the anchoring residue and the proline residue preceding it. Because Pro-Met and
      Pro-His sequences are rare in proteins, this sequence-specific cleavage is
      potentially useful for the removal of the fusion tags from the bioengineered
      fusion proteins.

PMID- 12526680
TI  - The role of oxoammonium cation in the SOD-mimic activity of cyclic nitroxides.
AB  - Cyclic nitroxides (RNO(*)) mimic the activity of superoxide dismutase (SOD) and
      demonstrate antioxidant properties in numerous in vitro and in vivo models. Their
      broad antioxidant activity may involve the participation of their reduced and
      oxidized forms, that is, hydroxylamine (RNO-H) and oxoammonium cation (RNO(+)).
      To examine this possibility we studied the reactions of RNO(*) and RNO(+) with
      HO(2)(*)/O(2)(*)(-) and with several reductants by pulse radiolysis and rapid
      mixing stopped-flow techniques. The oxoammonium cations were generated by
      electrochemical and radiolytic oxidation of 2,2,6,6-tetramethylpiperidinoxyl
      (TPO) and 3-carbamoyl-2,2,5,5-tetramethylpyrrolidinoxyl (3-CP). The rate constant
      for the reaction of RNO(*) with HO(2)(*) to form RNO(+) was determined to be (1.2
      +/- 0.1) x 10(8) for TPO and (1.3 +/- 0.1) x 10(6) M(-)(1) s(-)(1) for 3-CP. The
      kinetics results demonstrate that the reaction of RNO(*) with HO(2)(*) proceeds
      via an inner-sphere electron-transfer mechanism. The rate constant for the
      reaction of RNO(*) with O(2)(*)(-) is lower than 1 x 10(3) M(-)(1) s(-)(1). The
      rate constant for the reaction of RNO(+) with O(2)(*)(-) was determined to be
      (3.4 +/- 0.2) x 10(9) for TPO(+) and (5.0 +/- 0.2) x 10(9) M(-)(1) s(-)(1) for 3
      CP(+). Hence, both nitroxides catalyze the dismutation of superoxide through the
      RNO(*)/RNO(+) redox couple, and the dependence of the catalytic rate constant,
      k(cat), on pH displayed a bell-shaped curve having a maximum around pH 4. The
      oxoammonium cation oxidized ferrocyanide and HO(2)(-) by a one-electron transfer,
      whereas the oxidation of methanol, formate, and NADH proceeded through a two
      electron-transfer reaction. The redox potential of RNO(*)/RNO(+) couple was
      calculated to be 0.75 and 0.89 V for 3-CP and TPO, respectively. The elucidated
      mechanism provides a clearer insight into the biological antioxidant properties
      of cyclic nitroxides that should permit design of even more effective
      antioxidants.

PMID- 12526681
TI  - Reaction of vinyl chloride with group 4 metal olefin polymerization catalysts.
AB  - The reactions of three types of group 4 metal olefin polymerization catalysts,
      (C(5)R(5))(2)ZrX(2)/activator, (C(5)Me(5))TiX(3)/MAO (MAO = methylalumoxane), and
      (C(5)Me(4)SiMe(2)N(t)Bu)MX(2)/activator (M = Ti, Zr), with vinyl chloride (VC)
      and VC/propylene mixtures have been investigated. Two general pathways are
      observed: (i) radical polymerization of VC initiated by radicals derived from the
      catalyst and (ii) net 1,2 VC insertion into L(n)MR(+) species followed by beta-Cl
      elimination. rac-(EBI)ZrMe(mu-Me)B(C(6)F(5))(3) (EBI = 1,2-ethylenebis(indenyl))
      reacts with 2 equiv of VC to yield oligopropylene, rac-(EBI)ZrCl(2), and
      B(C(6)F(5))(3). This reaction proceeds by net 1,2 VC insertion into rac
      (EBI)ZrMe(+) followed by fast beta-Cl elimination to yield [rac
      (EBI)ZrCl][MeB(C(6)F(5))(3)] and propylene. Methylation of rac-(EBI)ZrCl(+) by
      MeB(C(6)F(5))(3)(-) enables a second VC insertion/beta-Cl elimination to occur.
      The evolved propylene is oligomerized by rac-(EBI)ZrR(+) as it is formed. At high
      Al/Zr ratios, rac-(EBI)ZrMe(2)/MAO catalytically converts VC to oligopropylene by
      1,2 VC insertion into rac-(EBI)ZrMe(+), beta-Cl elimination, and realkylation of
      rac-(EBI)ZrCl(+) by MAO; this process is stoichiometric in Al-Me groups. The
      evolved propylene is oligomerized by rac-(EBI)ZrR(+). Oligopropylene end group
      analysis shows that the predominant chain transfer mechanism is VC insertion/beta
      Cl elimination/realkylation. In the presence of trace levels of O(2), rac
      (EBI)ZrMe(2)/MAO polymerizes VC to poly(vinyl chloride) (PVC) by a radical
      mechanism initiated by radicals generated by autoxidation of Zr-R and/or Al-R
      species. CpTiX(3)/MAO (Cp = C(5)Me(5); X = OMe, Cl) initiates radical
      polymerization of VC in CH(2)Cl(2) solvent at low Al/Ti ratios under anaerobic
      conditions; in this case, the source of initiating radicals is unknown. Radical
      VC polymerization can be identified by the presence of terminal and internal
      allylic chloride units and other "radical defects" in the PVC which arise from
      the characteristic chemistry of PCH(2)CHCl(*) macroradicals. However, this test
      must be used with caution, since the defect units can be consumed by
      postpolymerization reactions with MAO.
      (C(5)Me(4)SiMe(2)N(t)Bu)MMe(2)/[Ph(3)C]][B(C(6)F(5))(4)] catalysts (M = Ti, Zr)
      react with VC by net 1,2 insertion/beta-Cl elimination, yielding
      [(C(5)Me(4)SiMe(2)N(t)Bu)MCl][B(C(6)F(5))(4)] species which can be trapped as
      (C(5)Me(4)SiMe(2)N(t)Bu)MCl(2) by addition of a chloride source. The reaction of
      rac-(EBI)ZrMe(2)/MAO or [(C(5)Me(4)SiMe(2)N(t)Bu)ZrMe][B(C(6)F(5))(4)] with
      propylene/VC mixtures yields polypropylene containing both allylic and vinylidene
      unsaturated chain ends rather than strictly vinylidene chain ends, as observed in
      propylene homopolymerization. These results show that the VC insertion of
      L(n)M(CH(2)CHMe)(n)R(+) species is also followed by beta-Cl elimination, which
      terminates chain growth and precludes propylene/VC copolymerization. Termination
      of chain growth by beta-Cl elimination is the most significant obstacle to metal
      catalyzed insertion polymerization/copolymerization of VC.

PMID- 12526682
TI  - Counterion-dependent excitonic spectra of tetra(p-carboxyphenyl)porphyrin
      aggregates in acidic aqueous solution.
AB  - Aggregates of the diacid form of tetra(p-carboxyphenyl)porphyrin (TCPP) are found
      to be stabilized in aqueous solution at low pH in the presence of poly(vinyl
      alcohol). At pH values in the range from about 1 to 4, a split Soret band is
      observed which is independent of counterion and tentatively assigned to a dimer
      species. As the pH is made lower than 1, the spectra evolve to reveal the
      presence of porphyrin aggregates. As in the case of the well-known aggregates of
      the related tetra(p-sulfonatophenyl)porphyrin (TSPP) diacid, the concentration of
      spectroscopically distinguishable aggregates increases with increasing ionic
      strength or decreasing pH. Unlike aggregates of TSPP, however, TCPP aggregates
      below pH 1 have visible absorption spectra which depend on the counterion, which
      is Cl(-) or NO(3)(-) in this study. In this work, we present visible absorption,
      light-scattering, and resonance Raman spectra of TCPP diacid in its monomer,
      dimer, and aggregated forms and attempt to understand the structural basis for
      counterion-dependent structure and excitonic coupling in the aggregates. Evidence
      is presented for intercalation of inorganic counterions between porphyrin
      molecules in the aggregate, an effect which to our knowledge has not been
      previously reported.

PMID- 12526683
TI  - Ordered mesoporous silica with large cage-like pores: structural identification
      and pore connectivity design by controlling the synthesis temperature and time.
AB  - FDU-1 silicas with large cage-like pores (diameter about 10 nm) were synthesized
      under acidic conditions from tetraethyl orthosilicate in the presence of a
      poly(ethylene oxide)-poly(butylene oxide)-poly(ethylene oxide) triblock copolymer
      template B50-6600 (EO(39)BO(47)EO(39)). High-resolution transmission electron
      microscopy and small-angle X-ray scattering provided strong evidence that FDU-1
      silica synthesized under typical conditions is a face-centered cubic Fm3m
      structure with 3-dimensional hexagonal intergrowth and is not a body-centered
      cubic Im3m structure, as originally reported. Samples synthesized in a wide range
      of conditions (initial temperatures from 298 to 353 K; hydrothermal treatment at
      333-393 K) exhibited similar XRD patterns and their nitrogen adsorption isotherms
      indicated a good-quality cage-like pore structure. The examination of low
      pressure nitrogen adsorption isotherms for FDU-1 samples, whose pore entrance
      diameters were evaluated using an independent method, allowed us to conclude that
      low-pressure adsorption was appreciably stronger for samples with smaller pore
      entrance sizes. This prompted us to examine low-pressure adsorption isotherms for
      a wide range of samples and led us to a conclusion that the FDU-1 pore entrance
      size can be systematically enlarged from about 1.3 nm (perhaps even lower) to at
      least 2.4 nm without an appreciable loss of uniformity by increasing the
      temperature of the hydrothermal treatment or the initial synthesis. Further
      enlargement of pore entrance size was achieved for sufficiently long hydrothermal
      treatment times at temperatures of 373 K or higher, as seen from the shape of
      nitrogen desorption isotherms. This allowed us to obtain samples with uniform
      pore sizes, high adsorption capacity, and with pore entrances enlarged so much
      that their size was similar to the size of the pore itself, resulting in a highly
      open porous structure. However, in the latter case, there was evidence that the
      pore entrance size distribution was quite broad.

PMID- 12526684
TI  - Silicalite crystal growth investigated by atomic force microscopy.
AB  - Atomic force microscopy has been used to image the various facets of two
      morphologically distinct samples of silicalite. The smaller (20 microm) sample A
      crystals show 1 nm high radial growth terraces. The larger (240 microm) sample B
      crystals show growth terraces 1 to 2 orders of magnitude higher than the terraces
      on sample A with growth edges parallel to the crystallographic axes. Moreover,
      the terraces on the (010) face are significantly higher than the terraces on the
      (100) face - inconsistent with the previously proposed 90 degrees intergrowth
      structure. Sample A highlights that under certain synthetic conditions,
      silicalite grows in a manner akin to zeolites Y and A, via the deposition of
      layers comprising, in the case of silicalite, pentasil chains. It is probable
      that the rate of terrace advance is identical on the (010) and (100) faces, and
      it is the rate of terrace nucleation that dictates the overall growth rate of
      each facet and hence the relative size expressed in the final crystal morphology.
      Analysis of the growth terraces of sample B and detailed consideration of the
      structures of both MFI, and a closely related material MEL, lead to the proposal
      of a generalized growth mechanism for silicalite including the incorporation of
      defects within the structure. These defects are thought to be responsible for
      both the relative and the absolute terrace heights observed and may also explain
      the hourglass phenomenon observed by optical microscopy. The implications of this
      growth mechanism, supported by results of infrared microscopy, generate a new
      dimension to the continuing debate on the existence of intergrowths within one of
      the most important structures relevant to zeolite catalysis.

PMID- 12526685
TI  - Multiple Li positions inside oxygen octahedra in lithiated TiO2 anatase.
AB  - Intercalation of Li in TiO2 anatase results in a phase separation in a Li-poor
      and a Li-rich phase. The local lithium configuration in the coexisting
      crystallographic phases is resolved by detailed analysis of neutron diffraction
      data. In each of the phases, two distinct positions within the octahedral
      interstices are found, with a temperature-dependent occupancy. A combination of
      quasi-elastic neutron scattering and force field molecular dynamics simulations
      shows that Li is hopping on a picosecond time scale between the two sites in the
      octahedral interstices. The results also suggest a specific Li arrangement along
      the crystallographic a direction, albeit without long range order. It is likely
      that multiple discrete Li sites within a distorted oxygen octahedron occur not
      only in intercalated TiO2 anatase but also in other (transition metal) oxides.

PMID- 12526687
TI  - Synthesis of target-specific radiolabeled peptides for diagnostic imaging.

PMID- 12526688
TI  - Synthesis of antisense oligonucleotides conjugated to a multivalent carbohydrate
      cluster for cellular targeting.
AB  - Carrier-mediated delivery holds great promise for significantly improving the
      cellular uptake and therefore the therapeutic efficacy of antisense
      oligonucleotides in vivo. A multivalent carbohydrate recognition motif for the
      asialoglycoprotein receptor has been designed for tissue- and cell-specific
      delivery of antisense drugs to parenchymal liver cells. To combine low molecular
      weight with high receptor affinity, the synthetic ligand contains three
      galactosyl residues attached to a cholane scaffold via epsilon-aminocapramide
      linkers. Three-dimensional structural calculations indicate that this unique
      design provides proper spacing and orientation of the three galactosyl residues
      to accomplish high affinity binding to the receptor. Covalent conjugation of the
      bulky carbohydrate cluster to oligonucleotides has been achieved by solid-phase
      synthesis using low-loaded macroporous resins and optimized synthesis protocols.

PMID- 12526689
TI  - Chemical defense in ascidians of the didemnidae family.
AB  - Fluorescent analogues (DB1 and TA1) of the secondary metabolites didemnin B (DB)
      and tamandarin A (TA) were synthesized to investigate the potential chemical
      defense mechanisms of tunicates in the family Didemnidae. These compounds were
      found to alter predator-prey relations. Five species of freshwater fish and one
      marine fish, the damselfish Amphiprion ocellaris, were acclimated to a diet of
      mosquito larvae. Fish showed an immediate, negative reaction to mosquito larvae
      treated with >/=5 ng of DB1 or TA1, with consumption of larvae resulting in
      regurgitation. Both freshwater and marine fish learned to avoid tainted prey by
      associating species of larvae with "distaste". Distaste for a given organism also
      arose when depsipeptides DB1 or TA1 were transferred to the fish from the
      surrounding medium. Fluorescence microscopy in fish indicated that a similar
      processing and localization followed ingestion and absorption of DB1 or TA1.
      Fluorescent labeling of DB or TA provided an ideal tool to conduct short-term
      studies of predator-prey relationships between fish and marine invertebrate
      larvae.

PMID- 12526690
TI  - Blue fluorescent antibodies as reporters of steric accessibility in virus
      conjugates.
AB  - Nonenveloped viruses provide the chemist with large, preassembled polyvalent
      protein scaffolds for modification. These structures are typically porous to
      small molecules but not to large ones. The solution-phase structures and
      reactivities of such assemblies may be substantially different than indicated by
      X-ray crystal structures. Here, the attachment of organic compounds to either the
      inside or outside surface of the cowpea mosaic virus (CPMV) coat protein was
      verified with an indicating antibody-antigen interaction. Antibody binding was
      subsequently blocked by the installation of poly(ethylene glycol) chains. These
      results typify the type of site-specific control that is available with CPMV and
      related virus building blocks.

PMID- 12526691
TI  - Tat-conjugated synthetic macromolecules facilitate cytoplasmic drug delivery to
      human ovarian carcinoma cells.
AB  - We have synthesized N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cell
      penetrating peptide Tat conjugates and evaluated their subcellular distribution
      in A2780 human ovarian carcinoma cells by confocal fluorescence microscopy and
      subcellular fractionation. Our data indicate the transport of these conjugates by
      a single Tat molecule to both the cytoplasm and nucleus via a nonendocytotic and
      concentration independent process. The uptake was observed to occur within 3 min,
      as confirmed by live cell microscopy. In contrast, HPMA copolymers lacking the
      Tat peptide were internalized solely by endocytosis. For the first time, Tat
      mediated cytoplasmic delivery of a polymer bound anticancer drug, doxorubicin,
      was also demonstrated. These findings establish the feasibility of overcoming
      major cellular and subcellular obstacles to intracellular macromolecular delivery
      and hold great promise for the development of polymer-based systems for the
      cytoplasmic delivery of therapeutic molecules.

PMID- 12526692
TI  - Endosomolysis by masking of a membrane-active agent (EMMA) for cytoplasmic
      release of macromolecules.
AB  - Endosomolysis, a critical barrier to efficient delivery of macromolecules such as
      nucleic acids, has been breached using a novel approach: endosomolysis by masking
      of a membrane-active agent (EMMA). To demonstrate the concept of EMMA, a cationic
      membrane-active peptide, melittin, was reversibly inhibited using a maleic
      anhydride derivative. At neutral pH, the lysines of melittin are covalently
      acylated with the anhydride, thereby inhibiting melittin's membrane disruption
      activity. Under acidic conditions such as those present within endosomes, the
      amide bond of the maleamate is cleaved, thus unmasking melittin. The active
      melittin can then disrupt the endosomal membrane resulting in release of
      biologically active molecules into the cytoplasm. This approach avoids cellular
      toxicity by restricting melittin's activity until it reaches the endosomal
      compartment. The utility of this approach was demonstrated by delivery
      phosphorodiamidate morpholino oligonucleotides (PMOs).

PMID- 12526693
TI  - Light-harvesting ionic dendrimer porphyrins as new photosensitizers for
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a promising therapeutic modality for treatment of
      solid tumors. In this study, third-generation aryl ether dendrimer porphyrins
      (DPs) with either 32 quaternary ammonium groups (32(+)DPZn) or 32 carboxylic
      groups (32(-)DPZn) were evaluated as a novel, supramolecular class of
      photosensitizers for PDT. DPs showed a different cell-association profile
      depending on the positive or negative charge on the periphery, and both DPs
      eventually localized in membrane-limited organelles. In contrast, protoporphyrin
      IX (PIX), which is a hydrophobic and relatively low molecular weight
      photosensitizer used as a control in this study, diffused through the cytoplasm
      except the nucleus. Confocal fluorescent imaging using organelle-specific dyes
      indicated that PIX induced severe photodamage to disrupt membranes and
      intracellular organelles, including the plasma membrane, mitochondrion, and
      lysosome. On the other hand, cells treated with DPs kept the characteristic
      fluorescent pattern of such organelles even after photoirradiation. However,
      notably 32(+)DPZn achieved remarkably higher (1)O(2)-induced cytotoxicity against
      LLC cells than PIX. Furthermore, both dendrimer porphyrins had far lower dark
      toxicity as compared with PIX, demonstrating their highly selective
      photosensitizing effect in combination with a reduced systemic toxicity.

PMID- 12526694
TI  - Non-natural cell surface receptors: synthetic peptides capped with N
      cholesterylglycine efficiently deliver proteins into Mammalian cells.
AB  - Protein toxins such as shiga toxin and cholera toxin penetrate into cells by
      binding small molecule-based cell surface receptors localized to cholesterol and
      sphingolipid-rich lipid raft subdomains of cellular plasma membranes. Molecular
      recognition between these toxins and their receptors triggers endocytic protein
      uptake through endogenous membrane trafficking pathways. We report herein the
      synthesis of functionally related non-natural cell surface receptors comprising
      peptides capped with N-cholesterylglycine as the plasma membrane anchor. The
      peptide moieties of these receptors were based on high-affinity epitopes of anti
      hemaglutinin antibodies (anti-HA), anti-Flag antibodies, and a moderate-affinity
      Strep Tag II peptide ligand of the streptavidin protein from Streptomyces
      avidini. These non-natural receptors were directly loaded into plasma membranes
      of Jurkat lymphocytes to display peptides from lipid rafts on the cell surface.
      Molecular recognition between these receptors and added cognate anti-HA, anti
      Flag, or streptavidin proteins resulted in rapid clathrin-mediated endocytosis;
      fluorescent target proteins were completely internalized within 4-12 h of protein
      addition. Analysis of protein uptake by epifluorescence microscopy and flow
      cytometry revealed intracellular fluorescence enhancements of 100-fold to 200
      fold (10 microM non-natural receptor) with typically >99% efficiency. This method
      enabled intracellular delivery of a functional Escherichia coli beta
      galactosidase enzyme conjugated to Protein A from Staphylococcus aureus. We
      termed this novel delivery strategy "synthetic receptor targeting", which is an
      efficient method to enhance macromolecular uptake by decorating mammalian cells
      with chemically defined synthetic receptors that access the molecular machinery
      controlling the organization of cellular plasma membranes.

PMID- 12526695
TI  - Preparation of bioconjugates by solid-phase conjugation to ion exchange matrix
      adsorbed carrier proteins.
AB  - A solid-phase conjugation method utilizing carrier protein bound to an ion
      exchange matrix was developed. Ovalbumin was adsorbed to an anion exchange matrix
      using a batch procedure, and the immobilized protein was then derivatized with
      iodoacetic acid N-hydroxysuccinimid ester. The activated protein was conjugated
      with glutathione, the conjugation ratio determined by acid hydrolysis, and amino
      acid analysis performed with quantification of carboxymethyl cysteine. Elution of
      conjugates from the resin by a salt gradient revealed considerable heterogeneity
      in the degree of derivatization, and immunization experiments with the eluted
      conjugates showed that the more substituted conjugates gave rise to the highest
      titers of glutathione antibodies. Direct immunization with the conjugates
      adsorbed to the ion exchange matrix was possible and gave rise to high titers of
      glutathione antibodies. Conjugates of ovalbumin and various peptides were
      prepared in a similar manner and used for production of peptide antisera by
      direct immunization with the conjugates bound to the ion exchanger. Advantages of
      the method are its solid-phase nature, allowing fast and efficient reactions and
      intermediate washings, and the ability to release conjugates from the solid phase
      under mild conditions.

PMID- 12526696
TI  - Reversible biotinylation phosphoramidite for 5'-end-labeling, phosphorylation,
      and affinity purification of synthetic oligonucleotides.
AB  - A fluoride/amine-cleavable phosphoramidite designed for biotinylation,
      phosphorylation, and affinity purification of synthetic oligonucleotides was
      synthesized and coupled efficiently to the 5'-end of DNA on a solid-phase
      automatic synthesizer. The two hydroxyl groups of diethyl
      bis(hydroxymethyl)malonate were used to link biotin and the 5'-end of DNA
      together through a diisopropylsilyl acetal functionality and a phosphate ester
      group, respectively. The DNA was cleaved from solid support and fully deprotected
      by treating with a mixture of MeNH(2) ( approximately 40%) and NH(4)OH (
      approximately 29%) (1:1, v/v, 65 degrees C, 30 min), and the linkage between
      biotin and DNA was found completely stable under these conditions. The
      biotinylated full-length DNA was efficiently attached to NeutrAvidin coated
      microspheres and failure sequences and other impurities were simply removed by
      washing with buffer and water. The microspheres were then treated with
      HF/pyridine/THF (rt, 1 h) and MeNH(2) ( approximately 40%, rt, 15 min)
      sequentially to yield high quality full-length 5'-end phosphorylated unmodified
      DNA as revealed by HPLC analysis. It is anticipated that this method will find
      applications in areas that require efficient isolation of 5'-end phosphorylated
      DNA from a complex mixture.

PMID- 12526697
TI  - Multiple-peptide conjugates for binding beta-amyloid plaques of Alzheimer's
      disease.
AB  - Formation of beta-amyloid plaques in Alzheimer's disease is initiated by
      intermolecular contact of the 5-amino acid sequence, KLVFF, in beta-amyloid
      peptides ranging in size from 40 to 43 residues. Through optimization of binding
      avidity using structure/function studies, we have found that the retro-inverso
      peptide, ffvlk, binds artificial fibrils made from Abeta(1)(-)(40) with moderate
      affinity (K(d) = 5 x 10(-)(7) M). Conjugates having two copies of this peptide,
      whether connected by a long poly(ethylene glycol) (PEG) spacer or just two amino
      acids, display about 100-fold greater affinity for fibrils. Placing six copies of
      ffvlk on a branched PEG resulted in a 10 000-fold greater affinity (K(d) = 1 x
      10(-)(10) M) than the monomer peptide. This increased affinity was accompanied by
      more effective inhibition of the thioflavin T fluorescence signal, which
      correlates with neurotoxicity of plaques and fibrils. We propose that conjugates
      bearing several copies of ffvlk may be useful as diagnostic and therapeutic
      agents for Alzheimer's disease.

PMID- 12526699
TI  - A high-capacity streptavidin-coated microtitration plate.
AB  - A majority of current immunoassays rely on capturing a specific analyte on a
      solid phase to allow the separation of the bound analyte from nonbound
      components. Streptavidin-coated microtitration plates are widely used for
      immobilization of capturing antibodies, since they provide a generic surface for
      immobilization of any biotinylated molecule and preserve biomolecule activity
      much better than direct passive adsorption. Our trials to further improve the
      properties of the plates resulted in a development of a modified plate, which has
      higher binding capacity than currently used control plate. The modified coat was
      prepared by cross-linking streptavidin chemically prior to adsorption onto the
      microtitration well surfaces. The binding capacities of the plates were measured
      with biotinylated, europium-labeled molecules and labeled antigen. The
      immunoassay performance of the plates was studied with noncompetitive, sandwich
      type assays of prostate specific antigen (PSA) and human chorionic gonadotropin
      (hCG). The maximum immobilization capacity of the modified plate was up to 2.5
      times higher than that of the control plate. The higher binding capacity was
      especially emphasized with small-size molecules. The modified high capacity plate
      increased the linear ranges of the immunoassays and thus delayed the high-dose
      hook effect. At high antigen concentrations the signal increased up to 59%, and
      at the conventional linear ranges of the assays, the increase was up to 29%. We
      conclude that the modified coating method will be valuable for the future
      miniaturized systems, where high immobilization capacity is needed at limited
      areas.

PMID- 12526698
TI  - Radiochemical investigations of (99m)Tc-N(3)S-X-BBN[7-14]NH(2): an in vitro/in
      vivo structure-activity relationship study where X = 0-, 3-, 5-, 8-, and 11
      carbon tethering moieties.
AB  - Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin
      releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and
      specificity. The GRPr is overexpressed on a variety of human cancer cells,
      including prostate, breast, lung, and pancreatic cancers. The specific aim of
      this study was to develop (99m)Tc-radiolabeled BBN analogues that maintain high
      specificity for the GRPr in vivo. A preselected synthetic sequence via solid
      phase peptide synthesis (SPPS) was designed to produce N(3)S-BBN (N(3)S =
      dimethylglycyl-l-seryl-l-cysteinylglycinamide) conjugates with the following
      general structure: DMG-S-C-G-X-Q-W-A-V-G-H-L-M-(NH(2)), where the spacer group, X
      = 0 (no spacer), omega-NH(2)(CH(2))(2)COOH, omega-NH(2)(CH(2))(4)COOH, omega
      NH(2)(CH(2))(7)COOH, or omega-NH(2)-(CH(2))(10)COOH. The new BBN constructs were
      purified by reversed phase-HPLC (RP-HPLC). Electrospray mass spectrometry (ES-MS)
      was used to characterize the nonmetalated BBN conjugates. Re(V)-BBN conjugates
      were prepared by the reaction of Re(V)gluconate with N(3)S-X-BBN[7-14]NH(2) (X =
      0 carbons, beta-Ala (beta-alanine), 5-Ava (5-aminovaleric acid), 8-Aoc (8
      aminooctanoic acid), and 11-Aun (11-aminoundecanoic acid)) with gentle heating.
      Re-N(3)S-5-Ava-BBN[7-14]NH(2) was also prepared by the reaction of
      [Re(V)dimethylglycyl-l-seryl-l-cysteinylglycinamide] with 5-Ava-BBN[7-14]NH(2).
      ES-MS was used to determine the molecular constitution of the new Re(V)
      conjugates. The (99m)Tc conjugates were prepared at the tracer level by each the
      prelabeling, post-conjugation and pre-conjugation, postlabeling approaches from
      the reaction of Na[(99m)TcO(4)] with excess SnCl(2), sodium gluconate, and
      corresponding ligand. The (99m)Tc and Re(V) conjugates behaved similarly under
      identical RP-HPLC conditions. In vitro and in vivo models demonstrated biological
      integrity of the new conjugates.

PMID- 12526700
TI  - Design, synthesis, and evaluation of gadolinium cationic lipids as tools for
      biodistribution studies of gene delivery complexes.
AB  - Gadolinium-chelating cationic lipids have been synthesized to obtain lipoplexes
      with MRI contrast properties. These compounds were designed to follow the
      biodistribution of synthetic DNA for gene delivery by nuclear magnetic resonance
      imaging. The lipid MCO-I-68 was synthesized, and chelate complexes with
      gadolinium were formed and characterized in terms of physicochemical and DNA
      binding properties. The transfection activity of MCO-I-68-Gd/DNA complexes was
      assayed in vitro on NIH 3T3. Different formulations of the product were tested.
      When up to 5% of the gadolinium lipid complexes were co-formulated with the
      cationic lipid RPR120535 used as a reference, the transfection levels were
      maintained as compared to RPR120535 alone. To date, only a liposomal formulation
      of a gadolinium-cationic lipid chelate without DNA had been observed using
      magnetic resonance imaging. In vivo intratumoral administration of MCO-I-68
      Gd/DNA lipoplexes to tumor model led to an important increase of the NMR signal.
      It was demonstrated that the new complexes also acted as transfection carriers
      when they were formulated from liposomes.

PMID- 12526701
TI  - Synthesis and binding properties of oligo-2'-deoxyribonucleotides conjugated with
      triple-helix-specific intercalators: benzo[e] and benzo[g] pyridoindoles.
AB  - DNA binding compounds, such as benzo[e] (BePI) and benzo[g] pyridoindole (BgPI)
      derivatives, exhibit preferential stabilization of triple helices. We report here
      the synthesis of a series of pyrimidine triple-helix-forming oligo-2'
      deoxyribonucleotides conjugated with these molecules. BePI was coupled to the 5
      position of 2'-deoxyuridine via two linkers of different sizes attached to its 11
      position and placed at either the 5'-end, inside the sequence, or at both the 5'
      end and the internal positions using periodate oxidation of a diol-containing
      oligonucleotide followed by reductive coupling with amino-linked BePI. The same
      BePI derivatives were also linked to the oligonucleotide chain via
      internucleotidic phosphorothiolate or phosphoramidate linkages. A mixture of
      diastereoisomers was prepared as well as separate pure Rp and Sp isomers. A BePI
      derivative, with two different linkers attached to its 3-position, and BgPI
      derivatives were also linked to the 5-position of a 2'-deoxyuridine located at
      either the 5'-end or inside the sequence, as well as to the beta- anomeric
      position of an additional 2'- deoxyribose placed inside the sequence. The binding
      properties of these oligonucleotide-benzopyridoindoles conjugates with their
      double-stranded DNA target was studied by absorption spectroscopy.

PMID- 12526702
TI  - Synthesis, characterization, and biological evaluation of technetium(III)
      complexes with tridentate/bidentate S,E,S/P,S coordination (E = O, N(CH(3)), S):
      a novel approach to robust technetium chelates suitable for linking the metal to
      biomolecules.
AB  - A novel type of mixed-ligand Tc(III) complexes, [Tc(SCH(2)CH(2)-E
      CH(2)CH(2)S)(PR(2)S)] (E = S, N(CH(3)); PR(2)S = phosphinothiolate with R = aryl,
      alkyl) is described. These "3+2"-coordinated complexes can be prepared in a two
      step reduction/substitution procedure via the appropriate chloro-containing
      oxotechnetium(V) complex [TcO(SES)Cl] [E=S, N(CH(3)]. Tc(III) compounds have been
      fully characterized both in solid and solution states and found to adopt the
      trigonal-bipyramidal coordination geometry. The equatorial trigonal plane is
      formed by three thiolate sulfur atoms, whereas the phosphorus of the bidentate
      P,S ligand and the neutral donor of the tridentate chelator occupy the apical
      positions. The (99)Tc(III) complexes have been proven to be identical with the
      (99m)Tc agents prepared at the no-carrier-added level by comparison of the
      corresponding UV/vis and radiometric HPLC profiles. Challenge experiments with
      glutathione clearly indicate that this tripeptide has no effect on the stability
      of the (99m)Tc complexes in solutions. Biodistribution studies have been carried
      out in rats at 5 and 120 min postinjection. The substituents at the bidentate P,S
      ligand significantly influence the biodistribution pattern. Remarkable
      differences are observed especially in brain, blood, lungs, and liver. All the
      complexes are able to penetrate the blood-brain barrier of rats and showed a
      relatively fast washout from the brain.

PMID- 12526703
TI  - Synthetic approaches to multivalent lipopeptide dendrimers containing cyclic
      disulfide epitopes of foot-and-mouth disease virus.
AB  - The synthesis of a multiantigenic peptide dendrimer incorporating four copies of
      a cyclic disulfide epitope has been undertaken. Since standard chemoselective
      ligation procedures involving thioether formation are inadvisable in the presence
      of a preformed disulfide, conjugation through a peptide bond between the
      lipidated branched lysine scaffold and a suitably protected version of the cyclic
      disulfide has been used instead. Several synthetic approaches to the partially
      protected cyclic disulfide peptide have been explored. The most effective
      involves building a minimally protected version of the peptide by Boc solid phase
      synthesis, using fluorenyl-based anchorings and cysteine protecting groups.
      Peptide-resin cleavage and cysteine deprotection/oxidation are performed
      simultaneously by base-promoted elimination. The cyclic disulfide epitope is
      readily obtained in sufficient amounts by this procedure and subsequently
      incorporated to the lipidated lysine core by peptide bond formation in solution.
      A final acid deprotection step in anhydrous HF yields a peptide construction
      containing a maximum of three copies of the cyclic disulfide epitope, the lower
      substitution being attributable to steric constraints. This immunogen has been
      successfully used in an experimental vaccination trial against foot-and-mouth
      disease virus.

PMID- 12526704
TI  - Signal peptide mimics conjugated to peptide nucleic acid: a promising solution
      for improving cell membrane permeability.
AB  - The specific binding ability and biostability of PNA (peptide nucleic acid) with
      DNA or RNA make PNA not only a good tool for the studies of molecular biology but
      also the candidate for gene-targeting drugs. However, the main obstacle for its
      potential usage as a therapeutic is the low cell uptake caused by the poor cell
      membrane permeability. In this paper the hydrophobic pentadecapeptide and two
      signal peptide mimics, hexa- and decapeptides ending with a positively charged
      amino acid, were proposed as the linked carrier for the transportation of PNA T10
      through the cell membrane; stable spin label was coupled to the peptide-PNA
      conjugate so that the ESR measurements can be used for the assessment of their
      transmembrane movements. The syntheses of spin-labeled peptide-PNA conjugates
      were carried out on MBHA resin with Boc strategy. The cell membrane permeability
      of the spin-labeled conjugates of peptides and PNA can be determined with ESR,
      during the incubation of erythrocyte with the samples. According to ESR
      measurements, the three conjugates exhibit enhanced uptake into erythrocytes. The
      hexa- and decapeptide-modified PNA showed suitable water solubility. The peptide
      PNA conjugates retained their binding ability to complementary DNA. The results
      suggest that peptide modification of PNA might be a promising solution for
      improving cell membrane permeability toward PNA.

PMID- 12526705
TI  - Synthesis and biological evaluation of folate receptor-targeted boronated PAMAM
      dendrimers as potential agents for neutron capture therapy.
AB  - Successful treatment of cancer by boron neutron capture therapy (BNCT) requires
      the selective delivery of (10)B to constituent cells within a tumor. The
      expression of the folate receptor is amplified in a variety of human tumors and
      potentially might serve as a molecular target for BNCT. In the present study we
      have investigated the possibility of targeting the folate receptor on cancer
      cells using folic acid conjugates of boronated poly(ethylene glycol) (PEG)
      containing 3rd generation polyamidoamine dendrimers to obtain (10)B
      concentrations necessary for BNCT by reducing the uptake of these conjugates by
      the reticuloendothelial system. First we covalently attached 12-15 decaborate
      clusters to 3rd generation polyamidoamine dendrimers. Varying quantities of PEG
      units with varying chain lengths were then linked to these boronated dendrimers
      to reduce hepatic uptake. Among all prepared combinations, boronated dendrimers
      with 1-1.5 PEG(2000) units exhibited the lowest hepatic uptake in C57BL/6 mice
      (7.2-7.7% injected dose (ID)/g liver). Thus, two folate receptor-targeted
      boronated 3rd generation polyamidoamine dendrimers were prepared, one containing
      approximately 15 decaborate clusters and approximately 1 PEG(2000) unit with
      folic acid attached to the distal end, the other containing approximately 13
      decaborate clusters, approximately 1 PEG(2000) unit, and approximately 1 PEG(800)
      unit with folic acid attached to the distal end. In vitro studies using folate
      receptor (+) KB cells demonstrated receptor-dependent uptake of the latter
      conjugate. Biodistribution studies with this conjugate in C57BL/6 mice bearing
      folate receptor (+) murine 24JK-FBP sarcomas resulted in selective tumor uptake
      (6.0% ID/g tumor), but also high hepatic (38.8% ID/g) and renal (62.8% ID/g)
      uptake, indicating that attachment of a second PEG unit and/or folic acid may
      adversely affect the pharmacodynamics of this conjugate.

PMID- 12526706
TI  - Modulation of the T cell response to beta-lactoglobulin by conjugation with
      carboxymethyl dextran.
AB  - We have previously prepared beta-lactoglobulin (beta-LG)-carboxymethyl dextran
      (CMD) conjugates with water-soluble carbodiimide and achieved reduced
      immunogenicity of beta-LG. In the present study, to elucidate the mechanism for
      the reduced immunogenicity of beta-LG, we investigated changes in the T cell
      response to beta-LG after conjugation with CMDs differing in molecular weight
      (about 40 and 162 kDa). Lymph node cells from BALB/c, C3H/He, and C57BL/6 mice
      that had been immunized with beta-LG or the conjugates were stimulated with beta
      LG, and the in vivo T cell response was then evaluated by BrdU (5-bromo-2'
      deoxyuridine) ELISA as the ex vivo proliferative response. T cells from the
      conjugate-immunized mice showed a lower proliferative response than those from
      the beta-LG-immunized mice. T cell epitope scanning, using synthesized peptides,
      showed that the T cell epitope profiles of the conjugates were similar to those
      of beta-LG, whereas the proliferative response to each epitope was reduced. These
      results indicate that the lower in vivo T cell response with the conjugates was
      not due to induction of conjugate-specific T cells, but due to a decrease in the
      number of beta-LG-specific T cells. After the lymph node cells from beta-LG
      immunized mice had been stimulated with beta-LG or the conjugates, the efficiency
      of the antigen presentation of the conjugate to beta-LG-specific T cells was
      evaluated by BrdU ELISA as the in vitro proliferative response. The antigen
      presentation of beta-LG to the T cells was reduced by conjugation with CMD. In
      addition, conjugation with CMD enhanced the resistance of beta-LG to cathepsin B
      and cathepsin D, which suggest that conjugation with CMD inhibited the
      degradation of beta-LG by proteases in APC and led to suppression of the
      generation of antigenic peptides including T cell epitopes from beta-LG. It is
      therefore considered that the suppressive effect on the generation of T cell
      epitopes reduced the antigen presentation of the conjugates and that this
      reduction led to a decrease in the number of beta-LG-specific T cells in vivo. As
      a result, the decreased help to B cells by T cells would have reduced the
      antibody response to beta-LG. We conclude that suppression of the generation of T
      cell epitopes by conjugation with CMD is important to the mechanism for the
      reduced immunogenicity of beta-LG.

PMID- 12526707
TI  - Lactose-installed poly(ethylene glycol)-poly(d,l-lactide) block copolymer
      micelles exhibit fast-rate binding and high affinity toward a protein bed
      simulating a cell surface. A surface plasmon resonance study.
AB  - Lactose molecules were installed on the surface of poly(ethylene glycol)-poly(d,l
      lactide) (PEG-PLA) block copolymer micelles in the scope of seeking specific
      recognition by cell surface receptors at hepatic sites. This, in turn, is
      expected to result in the formation of a complex displaying prolonged retention
      times and thus enhanced cellular internalization by receptor-mediated
      endocytosis. The so-obtained particles based on a block copolymer of molecular
      weight 9400 g/mol (4900/4500 g/mol for the PEG and PLA blocks, respectively) were
      found to have an average hydrodynamic diameter of 31.8 nm, as measured by dynamic
      light scattering. Further, the particle size distribution (micro(2)/Gamma(2)) was
      found to be lower than 0.08. Lactose-PEG-PLA micelles (Lac-micelles) were then
      injected over a gold surface containing Ricinus communis agglutinin lectins
      simulating the aforementioned glycoreceptors, and their interaction was studied
      by surface plasmon resonance. Then, a kinetic evaluation was carried out, by
      fitting the observed data mathematically. It appears that Lac-micelles bind in a
      multivalent manner to the lectin protein bed, which logically results in low
      dissociation constants. Micelles bearing a ligand density of 80% (Lac-micelles
      80%: 80 lactose molecules per 100 copolymer chains) exhibit fast association
      phases (k(a1) = 3.2 x 10(4) M(-)(1) s(-)(1)), but also extremely slow
      dissociation phases (k(d1) = 1.3 x 10(-)(4) s(-)(1)). Recorded sensorgrams were
      fitted with a trivalent model, conveying a calculated equilibrium dissociation
      constant (K(D1) = k(d1)/k(a1)) of about 4 nM. The importance of cooperative
      binding was also assessed, by preparing Lac-micelles bearing different ligand
      densities, and by discussing the influence of the latter on kinetic constants.
      Interestingly enough, whereas Lac-micelles 80% bind in a trivalent manner to the
      protein bed, Lac-micelles 20% are still capable of forming bivalent complexes
      with the same protein bed (K(D1) = 1360 nM). Therefore, despite enhanced kinetic
      values brought about by a supplementary bond, lower ligand densities appear to be
      more effective on a molecular basis.

PMID- 12526708
TI  - A stable bis-allyloxycarbonyl biotin aldehyde derivative for biotinylation via
      reductive alkylation: application to the synthesis of a biotinylated doxorubicin
      derivative.
AB  - A novel, stable, biotin aldehyde derivative is reported in which the biotin
      moiety is N1,N3-protected by the allyloxycarbonyl group. The derivative is stable
      to sodium cyanoborohydride mediated reductive alkylation and is cleaved under
      mild Pd [0] catalysis. This novel biotin aldehyde should have wide application in
      avidin- and streptavidin-based detection systems and bioassays. The derivative is
      utilized in the synthesis of a biotinylated doxorubicin analogue that retains
      topoisomerase activity.

PMID- 12526709
TI  - Spectroscopic study and evaluation of red-absorbing fluorescent dyes.
AB  - The spectroscopic characteristics (absorption, emission, and fluorescence
      lifetime) of 13 commercially available red-absorbing fluorescent dyes were
      studied under a variety of conditions. The dyes included in this study are
      Alexa647, ATTO655, ATTO680, Bodipy630/650, Cy5, Cy5.5, DiD, DY-630, DY-635, DY
      640, DY-650, DY-655, and EVOblue30. The thorough characterization of this class
      of dyes will facilitate selection of the appropriate red-absorbing fluorescent
      labels for applications in fluorescence assays. The influences of polarity,
      viscosity, and the addition of detergent (Tween20) on the spectroscopic
      properties were investigated, and fluorescence correlation spectroscopy (FCS) was
      utilized to assess the photophysical properties of the dyes under high excitation
      conditions. The dyes can be classified into groups based on the results
      presented. For example, while the fluorescence quantum yield of ATTO655, ATTO680,
      and EVOblue30 is primarily controlled by the polarity of the surrounding medium,
      more hydrophobic and structurally flexible dyes of the DY-family are strongly
      influenced by the viscosity of the medium and the addition of detergents.
      Covalent binding of the dyes to biotin and subsequent addition of streptavidin
      results in reversible fluorescence quenching or changes in the relaxation time of
      other photophysical processes of some dyes, most likely due to interactions with
      tryptophan residues in the streptavin binding site.

PMID- 12526710
TI  - Capture of peptides with N-terminal serine and threonine: a sequence-specific
      chemical method for Peptide mixture simplification.
AB  - The objective of this study was to evaluate a sequence-specific chemistry for the
      ability to specifically capture peptides that contain N-terminal serine or
      threonine residues from mixtures. The first step is the oxidation of the 1,2
      amino alcohol structure -CH(NH(2))CH(OH)- of peptides containing N-terminal
      serine or threonine with periodate. The newly formed aldehyde reacts with a
      labeling reagent containing a hydrazide, RCONHNH(2), to form a hydrazone-peptide
      conjugate, RCONHN=CH-peptide. Biotin-labeled conjugates can then be isolated by
      affinity purification with streptavidin. The method described in this report can
      be useful in simplifying the complex mixtures of peptides that are generated in
      typical proteomic analysis, where proteins are digested with trypsin and analyzed
      using liquid chromatography mass spectrometry data. The sequence-specific peptide
      selection not only reduces the complexity of digest mixtures, but also provides
      additional information for peptide identification. The targeted peptides are
      those that have either serine or threonine adjacent to a protease cleavage site.
      The sequence information should greatly aid in both database matching for protein
      identification and for de novo sequence determination.

PMID- 12526711
TI  - Vanadyl-thiazolidinedione combination agents for diabetes therapy.
AB  - A series of vanadium compounds, chelated by ligands containing a
      thiazolidinedione moiety as an additional insulin-enhancing component, were
      produced in this study to create potentially synergistic compounds. A set of four
      bifunctional ligand precursors were synthesized: (+/-)-5-[4-[(5-hydroxy-4-oxo-4H
      pyran-2-ylmethyl)amino]benzyl]thiazolidine-2,4-dione (HL(1)), (+/-)-5-[4-[(5
      hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)amino]benzyl]thiazolidine
      2,4-dione (HL(2)), 5-[4-(5-hydroxy-4-oxo-4H-pyran-2
      ylmethoxy)benzylidene]thiazolidine-2,4-dione (HL(3)), and (+/-)-5-[4-(5-hydroxy-4
      oxo-4H-pyran-2-ylmethoxy)benzyl]thiazolidine-2,4-dione (HL(4)), each containing a
      metal chelating portion as well as a thiazolidinedione moiety. From this set of
      ligand precursors, air-stable VO(L(1))(2), VO(L(3))(2), and VO(L(4))(2) were
      prepared. The four ligand precursors and three complexes were tested for insulin
      enhancing potential in STZ-diabetic rats and compared to rosiglitazone and BMOV,
      respectively. Both the ligand precursors HL(1) and HL(3) showed enhanced activity
      compared with that of rosiglitazone. The complex VO(L(3))(2) showed the most
      efficacious hypoglycemic effects in this study; however, neither additive nor
      synergistic effects were observed using this acute animal model.

PMID- 12526712
TI  - Novel shielded transferrin-polyethylene glycol-polyethylenimine/DNA complexes for
      systemic tumor-targeted gene transfer.
AB  - Tumor-targeting DNA complexes which can readily be generated by the mixing of
      stable components and freeze-thawed would be very advantageous for their
      subsequent application as medical products. Complexes were generated by the
      mixing of plasmid DNA, linear polyethylenimine (PEI22, 22 kDa) as the main DNA
      condensing agent, PEG-PEI (poly(ethylene glycol)-conjugated PEI) for surface
      shielding, and Tf-PEG-PEI (transferrin-PEG-PEI) to provide a ligand for receptor
      mediated cell uptake. Within the shielding conjugates, PEG chains of varying size
      (5, 20, or 40 kDa) were conjugated with either linear PEI22 (22 kDa) or branched
      PEI25 (25 kDa). The three polymer components were mixed together at various
      ratios with DNA; particle size, surface charge, in vitro transfection activity,
      and systemic gene delivery to tumors was investigated. In general, increasing the
      proportion of shielding conjugate in the complex reduced surface charge, particle
      size, and in vitro transfection efficiency in transferrin receptor-rich K562
      cells. The particle size or surface charge of the complexes containing the PEG
      PEI conjugate did not significantly change after freeze-thawing, while complexes
      without the shielding conjugate aggregated. Complexes containing PEG-PEI
      conjugate efficiently transfected K562 cells after freeze-thawing. Furthermore
      the systemic application of freeze-thawed complexes exhibited in vivo tumor
      targeted expression. For complexes containing the luciferase reporter gene the
      highest expression was found in tumor tissue of mice. An optimum formulation for
      in vivo application, PEI22/Tf-PEG-PEI/PEI22-PEG5, containing plasmid DNA encoding
      for the tumor necrosis factor (TNF-alpha), inhibited tumor growth in three
      different murine tumor models. These new DNA complexes offer simplicity and
      convenience, with tumor targeting activity in vivo after freeze-thawing.

PMID- 12526713
TI  - Synthesis of maleimide-activated carbohydrates as chemoselective tags for site
      specific glycosylation of peptides and proteins.
AB  - An array of maleimide-activated mono- and oligosaccharides were synthesized to
      permit site-specific glycosylation of cysteine-containing peptides and proteins.
      Maleimide-activated monosaccharides, in which the native alpha- or beta-O
      glycosidic linkages found for nonreducing terminal sugars of native glycoproteins
      are preserved, were prepared using 2'-aminoethyl glycosides as the key
      intermediates. In addition, a native high-mannose type oligosaccharide,
      Man(9)GlcNAc(2)Asn, was converted into its maleimide-activated form by taking
      advantage of the existing amino group in the Asn portion. The application of
      these maleimide-activated carbohydrates was exemplified by the site-specific
      glycosylation of a 36-mer HIV-1 gp41 peptide, T20, which is a potent inhibitor
      against HIV infection. The chemoselective ligation was found to be rapid, highly
      efficient, and essentially quantitative. Tagging the biologically active peptide
      with a mannose and/or oligomannose moiety will be useful for targeting the drug
      to macrophage and dendritic cells, which are primary targets for HIV-1 infection
      and are expressing mannose- and oligomanose-specific receptors on their surface.
      In combination with site-specific mutagenesis, the maleimide-activated
      carbohydrates can serve as generally applicable tags for site-specific
      glycosylation of proteins via the highly efficient maleimide-thiol ligation
      reaction.

PMID- 12526714
TI  - Solid-phase synthesis of multivalent glycoconjugates on a DNA synthesizer.
AB  - Carbohydrate-oligonucleotide conjugates and glycodendrimers were synthesized
      utilizing a DNA synthesizer. The synthesis of multivalent glycoconjugates on
      solid-phase allows custom tailoring of their structure to the requirements of
      biological assays within hours, as opposed to traditional approaches that require
      weeks or months of work in the laboratory. Therefore it will become much easier
      to investigate carbohydrate-protein interactions and optimize for objectives such
      as the receptor-mediated targeting of antisense oligonucleotides.

PMID- 12526715
TI  - Structural effects of carbohydrate-containing polycations on gene delivery. 1.
      Carbohydrate size and its distance from charge centers.
AB  - Cationic polymers have the ability to bind plasmid DNA (pDNA) through
      electrostatic interactions and condense it into particles that can be readily
      endocytosed by cultured cells. The effects that polycation structure has on
      toxicity and gene delivery efficiency are investigated here by synthesizing a
      series of amidine-based polycations that contain the carbohydrates d-trehalose
      and beta-cyclodextrin (CD) within the polycation backbone. The carbohydrate size
      (trehalose vs CD) and its distance from the charge centers affect the gene
      delivery behavior in BHK-21 cells. It is found that as the charge center is
      further removed from the carbohydrate unit, the toxicity is increased. Also, as
      the size of the carbohydrate moiety is enlarged from trehalose to beta
      cyclodextrin, the toxicity is reduced. The absence of a carbohydrate in the
      polycation produces high toxicity. All carbohydrate polycations transfect BHK-21
      cells to approximately the same level of gene expression.

PMID- 12526716
TI  - Structural effects of carbohydrate-containing polycations on gene delivery. 2.
      Charge center type.
AB  - Recent polycation structure-gene delivery studies reveal that subtle changes in
      the molecular structure of polycations have substantial influences on DNA-binding
      and condensation and on in vitro toxicity and gene delivery efficiency. In Part 1
      of this structure-property study using carbohydrate-containing polycations (1),
      it is demonstrated that as the amidine charge center is removed further from the
      carbohydrate unit within the polycation structure, the toxicity increases.
      Inclusion of larger carbohydrate species within the polycation backbone also
      reduces the toxicity. Here, the effect that polycation charge center type has on
      toxicity and gene delivery efficiency is investigated. A series of quaternary
      ammonium polycations containing N,N,N',N'-tetramethyl-1,6-hexanediamine, d
      trehalose, and beta-cyclodextrin are synthesized in order to elucidate the
      effects of charge center type (by comparison to the data given in Part 1) on gene
      delivery. In all cases, it is found that the quaternary ammonium analogues
      exhibit lower gene expression values and similar toxicities to their amidine
      analogues. Additionally, transfection experiments conducted in the presence of
      chloroquine reveal increased gene expression from quaternary ammonium containing
      polycations and not from their amidine analogues.

PMID- 12526717
TI  - A concise synthesis of the 3-O-beta-D- and 4'-O-beta-D-glucuronide conjugates of
      trans-resveratrol.
AB  - trans-Resveratrol ((E)-3,4',5-trihydroxystilbene, 1) is a phytoalexin produced
      naturally in plants and grape skins as a stress metabolite protecting against
      fungal attack. Widespread interest in this apparently structurally simple
      molecule and synthetic stilbene analogues has arisen in recent years due to the
      discovery of its antioxidant, antiinflammatory, and anti-carcinogenic activities,
      among others. Although O-conjugation with glucuronic acid in vivo is known to
      represent a significant metabolic pathway for polyphenolic compounds in general
      and 1 in particular, preclinical studies have been hampered by the lack of
      chemically pure, completely characterized reference standards of both
      regioisomeric 3-O-beta-d- and 4'-O-beta-d-glucuronide conjugates of 1 for
      adequate identification and quantification of these significant metabolites. The
      present work describes a concise, convergent synthesis of both 3-O-beta-d- and 4'
      O-beta-d-glucuronide conjugates of 1 using a strategy based on a novel Heck
      coupling of iodoaryl-O-beta-d-glucuronate esters with appropriately substituted
      styrenes, such that highly pure multimilligram to gram quantities of both the 3-O
      beta-d- and 4'-O-beta-d-glucuronide conjugates of 1 can now be conveniently
      synthesized.

PMID- 12526718
TI  - Biohydrogen production from sucrose using the visible light sensitization of
      artificial Zn chlorophyll-a.
AB  - A photoinduced hydrogen production system that couples sucrose degradation with
      invertase and glucose dehydrogenase (GDH) and hydrogen production with colloidal
      platinum as a catalyst using visible light-induced photosensitization of
      artificial Zn chlorophyll-a (Zn Chl-a) has been developed. Continuous hydrogen
      gas production over more than 240 min was observed when the reaction mixture
      containing sucrose, invertase, GDH, nicotinamide adenine dinucreotide (NAD(+)),
      Zn Chl-a, methyl viologen (MV(2+), an electron relay reagent), and colloidal
      platinum was irradiated by visible light. Zn Chl-a was superior to that of Mg Chl
      a in photostability and photosensitization activity.

PMID- 12526719
TI  - Religion, spirituality and health: an American physician's response.

PMID- 12526720
TI  - Researchers as guinea pigs.

PMID- 12526721
TI  - The hospitalist: a US model ripe for importing?

PMID- 12526722
TI  - Growth and morbidity in children in the Aboriginal Birth Cohort Study: the urban
      remote differential.
AB  - OBJECTIVES: To describe the prevalence of markers of growth, chronic and
      infectious disease in peripubertal Aboriginal children living in the Darwin
      Health Region in the "Top End" of the Northern Territory, and to compare
      prevalence between children living in urban and remote areas. DESIGN: Cross
      sectional survey nested in a prospective birth cohort. SUBJECTS: 482 children
      living in the region who were recruited at birth (Jan 1987 to Mar 1990) and were
      followed up between 1998 and 2001, when aged 8-14 years. MAIN OUTCOME MEASURES:
      Selected parameters of growth and nutrition, infectious disease and potential
      markers of chronic adult disease were compared between children living at follow
      up in suburban situations in Darwin-Palmerston (urban) and those living in rural
      communities with an Aboriginal council (remote). RESULTS: Remote children were
      shorter than urban children (mean height, 141.7 v 146.3 cm; P < 0.001), lighter
      (median weight, 30.3 v 37.1 kg; P < 0.001) and had lower body mass index (median,
      15.3 v 17.9 kg/m(2); P < 0.001) and haemoglobin level (mean, 125.1 v 130.9 g/L; P
      < 0.001). Some potential markers of adult chronic disease were higher in urban
      than remote children: systolic blood pressure (mean, 109.6 v 106.2 mmHg; P =
      0.004), and levels of total cholesterol (4.3 v 4.0 mmol/L; P < 0.001), high
      density lipoprotein cholesterol (mean, 1.4 v 1.2 mmol/L; P < 0.001) and insulin
      (median, 7 v 4 mU/L; P = 0.007). Diastolic blood pressure, levels of red cell
      folate, serum glucose and low-density lipoprotein cholesterol, and urinary
      albumin-creatinine ratio did not differ by location. The prevalence of visible
      infections was also higher in remote than urban children (P < 0.05). CONCLUSION:
      As some markers of health differ between peripubertal Aboriginal children living
      in urban areas and those in remote areas, results of surveys in remote areas
      cannot be generalised to urban Aboriginal populations.

PMID- 12526723
TI  - Bupropion poisoning: a case series.
AB  - OBJECTIVE: To investigate the toxicity of bupropion hydrochloride in deliberate
      self-poisoning in adults and accidental ingestion by children. DESIGN AND
      SETTING: Prospective study of cases identified from calls to the New South Wales
      Poisons Information Centre (NSW PIC), with follow-up through hospital medical
      records. PARTICIPANTS: Patients with bupropion poisoning managed in hospital,
      about whom the NSW PIC was contacted for advice, from 1 November 2000 to 31 July
      2001 (59 adults and 10 children). MAIN OUTCOME MEASURES: Clinical effects,
      adverse outcomes (including seizures and death) and treatment. RESULTS: 45 of the
      59 adults were followed up (76%), 19 of whom had taken bupropion alone. Major
      clinical effects of bupropion included sinus tachycardia (83%), hypertension
      (56%), seizures (37%), gastrointestinal symptoms (37%) and agitation (32%).
      Seizures were dose-dependent, with those having seizures ingesting a
      significantly higher median dose (P = 0.02). All seizures were brief and self
      limiting. 29 patients received decontamination therapy. 10 patients required
      pharmacological sedation, 10 were admitted to intensive care and six were
      intubated. None died. Eight of 10 accidental ingestions by children were followed
      up (80%); one child had symptoms (vomiting and hallucinations). CONCLUSIONS:
      Bupropion overdose caused significant clinical effects in adults, but few in
      children.

PMID- 12526724
TI  - An evaluation of a SAFE-style trachoma control program in Central Australia.
AB  - OBJECTIVES: To evaluate the effectiveness of a trachoma control program in a
      remote community before and after major environmental health improvements.
      DESIGN: Before-and-after cross-sectional design. The control program was in three
      rounds - each consisting of community census, screening of children < 13 years,
      health promotion activities and antibiotic treatment. There were two housing and
      infrastructure surveys. INTERVENTIONS: Treatment of affected children and their
      households with azithromycin at baseline, 7 and 21 months, and health promotions.
      Housing and sewerage infrastructure improvements were completed at 12 months.
      SETTING: Large, remote Central Australian Aboriginal community, 1998-2000.
      PARTICIPANTS: All community residents. MAIN OUTCOME MEASURES: Prevalence of
      active trachoma among children under 13 years; community population changes; and
      adequacy of housing facilities for healthy living practices. RESULTS: The
      prevalence of trachoma among children was 40% (95% CI, 32%-46%) at baseline, 33%
      (95% CI, 26%-40%) at 7 months' follow-up and 37% (95% CI, 29%-46%) at 21 months.
      These proportions were neither clinically nor statistically significantly
      different. There was a high degree of population mobility over the study period,
      with only 32% of residents appearing in all three censuses. The proportion of
      houses with completely adequate facilities increased from 0 to 16%. CONCLUSIONS:
      Population mobility (both within and between communities), inadequate housing and
      continued crowding (despite improvements), as well as uncertainty about
      compliance with antibiotic treatment, are the likely factors contributing to the
      lack of effect of this trachoma control program. Because of high population
      mobility, a region-wide approach is needed for effective trachoma control.

PMID- 12526725
TI  - Experimental human infection with the dog hookworm, Ancylostoma caninum.
AB  - OBJECTIVE: To investigate possible routes for human infection by the dog hookworm
      (Ancylostoma caninum). DESIGN, SETTING AND PARTICIPANT: Relatively small numbers
      of infective larvae were administered orally and percutaneously to an informed
      healthy volunteer (J K L) under medical supervision, at intervals between May
      1998 and May 1999. MAIN OUTCOME MEASURES: Symptoms; weekly blood eosinophil
      counts; faecal microscopy. RESULTS: A marked blood eosinophilia followed a single
      oral exposure to 100 infective larvae, while faecal examination remained
      negative. Eosinophil counts then declined gradually, although a rapid,
      spontaneous rise several months later, at the beginning of spring, possibly
      indicated reactivation of dormant larvae. Blood eosinophil numbers did not rise
      significantly after percutaneous infection with 200 larvae. A subsequent,
      smaller, oral inoculum of 20 larvae provoked an eosinophil response similar to
      that of the first experiment. CONCLUSIONS: Our findings suggest that, following
      ingestion, some infective larvae of A. caninum develop directly into adult worms
      in the human gut (as they do in dogs). While the percutaneous route might be the
      most common means of human exposure to canine hookworm larvae, leading generally
      to subclinical infection, oral infection may be more likely to provoke
      symptomatic eosinophilic enteritis.

PMID- 12526726
TI  - The effect of recalling paracetamol on hospital admissions for poisoning in
      Western Australia.
AB  - OBJECTIVES: To assess the effect of two recalls of paracetamol products on rates
      of intentional and unintentional overdoses of paracetamol in all age groups, as
      well as any effect on poisoning by other agents. DESIGN: A before-and-after
      epidemiological study using data from the Western Australian Health Services
      Research Linked Database, which records all admissions to public and private
      hospitals throughout the State. MAIN OUTCOME MEASURES: Hospital admissions in
      Western Australia for poisonings with all agents, including paracetamol and other
      over-the-counter analgesics. RESULTS: There were 11 752 admissions for poisoning
      from 1996 to 2001. Paracetamol was the primary poisoning agent in 2266 (19.3%)
      admissions, aspirin in 120 (1%) and ibuprofen in 277 (2%). There was a
      significant decrease in the admission rate for paracetamol poisoning when sales
      were restricted in 2000 (rate ratio, 0.82; 95% CI, 0.68-0.99) compared with the
      same period in other years. There was no increase in poisoning with other agents
      at this time. However, admissions for paracetamol overdose also showed a large
      random variation that tended to obscure any effect. CONCLUSIONS: Our study
      highlights the need to control for random as well as seasonal fluctuations in
      admission rates, and for restrictions on paracetamol sales to last for several
      months across all retail outlets. Limiting access to paracetamol may reduce
      paracetamol poisonings without a coincident increase in the use of other agents

PMID- 12526727
TI  - Palmar erythema and hoarseness: an unusual clinical presentation of sarcoidosis.
AB  - Palmar erythema is a very unusual manifestation of sarcoidosis. We report on a
      patient whose presenting features of sarcoidosis were palmar erythema and a
      hoarse voice. The diagnosis was confirmed by palmar skin biopsy and the patient
      responded well to treatment with prednisolone.

PMID- 12526728
TI  - Psychological outcomes and risk perception after genetic testing and counselling
      in breast cancer: a systematic review.
AB  - OBJECTIVES: To conduct a systematic review of the effects of genetic counselling
      and testing for familial breast cancer on women's perception of risk and
      psychological morbidity. DATA SOURCES: MEDLINE, PsychLIT and EMBASE were searched
      for the period 1980-2001. STUDY SELECTION: Studies were eligible if published in
      a peer-reviewed journal in English, included women with a family history of
      breast cancer who underwent genetic counselling or testing and had either a
      randomised controlled trial or prospective design, with a pre- and at least one
      post-counselling assessment. DATA SYNTHESIS: As there was considerable
      heterogeneity in populations and measures, results were summarised rather than
      subjected to meta-analysis. RESULTS: Overall, genetic counselling and testing
      appear to produce psychological benefits and to improve accuracy of risk
      perception. Carriers of mutations in cancer predisposition genes did not
      experience significant increases in depression and anxiety after disclosure of
      their mutation status, while non-carriers experienced significant relief. Women
      who were tested but declined to learn their results seemed to be at greater risk
      of a worse psychological outcome. CONCLUSIONS: To date, the data on psychological
      outcomes after genetic counselling and testing are reassuring. However, few
      studies used a randomised trial design, limiting the strength of the conclusions.
      Follow-up to date has been short, and we know little about the long-term impact
      of testing on patient behaviours, perceptions and psychological state.

PMID- 12526729
TI  - Management of chronic hepatitis B virus infection in remote-dwelling Aboriginals
      and Torres Strait Islanders: an update for primary healthcare providers.
AB  - Chronic HBV infection is common in remote Aboriginal and Torres Strait Islander
      communities, where resources are scarce and patients may have several concurrent
      illnesses. The management of chronic HBV infection has changed over recent years,
      with greater application of serological and radiological investigations and new,
      more acceptable treatments for chronic liver disease, cirrhosis and
      hepatocellular carcinoma. Optimal follow-up procedures for patients with chronic
      HBV infection are still being debated, but may not be applicable to Aboriginal
      and Torres Strait Islander communities where factors such as endemicity,
      remoteness, frequent comorbidities, shorter life expectancy and cultural
      differences in health priorities must be taken into consideration. We have
      defined an algorithm to assist primary care providers caring for patients with
      chronic HBV infection in Aboriginal and Torres Strait Islander communities.
      Patients are divided into one of three categories for follow-up and referral
      based on clinical features, and results of liver enzyme and serological tests.

PMID- 12526730
TI  - Religion, spirituality and health: how should Australia's medical professionals
      respond?
AB  - Greater participation in religious activities is associated with better health
      outcomes. In the US, most inpatients have religious needs, but physicians address
      them only occasionally and infrequently refer patients to clergy. US medical
      students are learning to do spiritual assessments and integrate the findings into
      patient management, which may reverse this. Religion does not play a central role
      in the lives of Australians as it does for US citizens. Research is required to
      better understand the spirituality of Australians, its relationship to health and
      the benefit, cost and acceptability of doctors enquiring into spirituality
      compared with spiritual advisers and counsellors.

PMID- 12526731
TI  - Injury caused by baby walkers.

PMID- 12526732
TI  - Opportunistic GP-based bowel cancer screening.

PMID- 12526733
TI  - GP meets the psychiatrist.

PMID- 12526734
TI  - Medical Professionalism Project.

PMID- 12526735
TI  - Developing a core clinical data set for cancer.

PMID- 12526737
TI  - Generalists and gerontology.

PMID- 12526736
TI  - Does intramuscular botulinum toxin A injection improve upper-limb function in
      children with hemiplegic cerebral palsy?

PMID- 12526738
TI  - Demography, recombination hotspot intensity, and the block structure of linkage
      disequilibrium.
AB  - BACKGROUND: Effective gene mapping based on genetic association data will require
      detailed knowledge of patterns of linkage disequilibrium (LD) in human
      populations. It has been recently suggested that linkage disequilibrium in humans
      may be organized in a block-like structure, with islands of high LD separated by
      regions of rapid breakdown of LD due to recombination hotspots. The experimental
      data to date, however, are limited, and fundamental questions remain about the
      implications of recombination rate heterogeneity. Here, we use computer
      simulations to evaluate how such heterogeneity influences patterns of LD, and we
      develop formal criteria to assess whether the patterns are functionally block
      like in the context of association mapping. RESULTS: Our analyses suggest that,
      even in models of extreme recombination rate heterogeneity, some human
      populations will have a functionally block-like structure to the pattern of LD,
      but others will not, depending on their precise demographic histories. In fact,
      for many models, we find that, following an LD-generating event, populations may
      move through discrete phases that can be functionally described as pre-block,
      block, and post-block. An analysis of observed and expected patterns of LD
      surrounding hotspots within the MHC Class II region confirms these theoretical
      expectations. CONCLUSIONS: Even if highly punctuated patterns of recombination
      are the rule, patterns of LD are still likely to show differences among
      populations and among genomic regions that are of practical importance in the
      design of genetic association studies. The notion that the average extent of LD
      is a useful concept for the design of association studies must be abandoned in
      light of the experimental and theoretical evidence.

PMID- 12526739
TI  - Fyn tyrosine kinase is a critical regulator of disabled-1 during brain
      development.
AB  - BACKGROUND: Disabled-1 (Dab1) is an intracellular adaptor protein that regulates
      migrations of various classes of neurons during mammalian brain development. Dab1
      function depends on its tyrosine phosphorylation, which is stimulated by Reelin,
      an extracellular signaling molecule. Reelin increases the stoichiometry of Dab1
      phosphorylation and downregulates Dab1 protein levels. Reelin binds to various
      cell surface receptors, including two members of the low-density lipoprotein
      receptor family that also bind to Dab1. Mutations in Dab1, its phosphorylation
      sites, Reelin, or the Reelin receptors cause a common phenotype. However, the
      molecular mechanism whereby Reelin regulates Dab1 tyrosine phosphorylation is
      poorly understood. RESULTS: We found that Reelin-induced Dab1 tyrosine
      phosphorylation in neuron cultures is inhibited by acute treatment with
      pharmacological inhibitors of Src family, but not Abl family, kinases. In
      addition, Reelin stimulates Src family kinases by a mechanism involving Dab1. We
      analyzed the Dab1 protein level and tyrosine phosphorylation stoichiometry by
      using brain samples and cultured neurons that were obtained from mouse embryos
      carrying mutations in Src family tyrosine kinases. We found that fyn is required
      for proper Dab1 levels and phosphorylation in vivo and in vitro. When fyn copy
      number is reduced, src, but not yes, becomes important, reflecting a partial
      redundancy between fyn and src. CONCLUSIONS: Reelin activates Fyn to
      phosphorylate and downregulate Dab1 during brain development. The results were
      unexpected because Fyn deficiency does not cause the same developmental phenotype
      as Dab1 or Reelin deficiency. This suggests additional complexity in the Reelin
      signaling pathway.

PMID- 12526741
TI  - Naip5 affects host susceptibility to the intracellular pathogen Legionella
      pneumophila.
AB  - BACKGROUND: Legionella pneumophila is a gram-negative bacterial pathogen that is
      the cause of Legionnaires' Disease. Legionella produces disease because it can
      replicate inside a specialized compartment of host macrophages. Macrophages
      isolated from various inbred mice exhibit large differences in permissiveness for
      intracellular replication of Legionella. A locus affecting this host-resistance
      phenotype, Lgn1, has been mapped to chromosome 13, but the responsible gene has
      not been identified. RESULTS: Here, we report that Naip5 (also known as Birc1e)
      influences susceptibility to Legionella. Naip5 encodes a protein that is
      homologous to plant innate immunity (so-called "resistance") proteins and has
      been implicated in signaling pathways related to apoptosis regulation. Detailed
      recombination mapping and analysis of expression implicates Naip5 in the
      Legionella permissiveness differences among mouse strains. A bacterial artificial
      chromosome (BAC) transgenic line expressing a nonpermissive allele of Naip5
      exhibits a reduction in macrophage Legionella permissiveness. In addition,
      morpholino-based antisense inhibition of Naip5 causes an increase in the
      Legionella permissiveness of macrophages. CONCLUSIONS: We conclude that
      polymorphisms in Naip5 are involved in the permissiveness differences of mouse
      macrophages for intracellular Legionella replication. We speculate that Naip5 is
      a functional mammalian homolog of plant "resistance" proteins that monitor for,
      and initiate host response to, the presence of secreted bacterial virulence
      proteins.

PMID- 12526740
TI  - Reelin activates SRC family tyrosine kinases in neurons.
AB  - BACKGROUND: Reelin is a large signaling molecule that regulates the positioning
      of neurons in the mammalian brain. Transmission of the Reelin signal to migrating
      embryonic neurons requires binding to the very-low-density lipoprotein receptor
      (VLDLR) and the apolipoprotein E receptor-2 (apoER2). This induces tyrosine
      phosphorylation of the adaptor protein Disabled-1 (Dab1), which interacts with a
      shared sequence motif in the cytoplasmic tails of both receptors. However, the
      kinases that mediate Dab1 tyrosine phosphorylation and the intracellular pathways
      that are triggered by this event remain unknown. RESULTS: We show that Reelin
      activates members of the Src family of non-receptor tyrosine kinases (SFKs) and
      that this activation is dependent on the Reelin receptors apoER2 and VLDLR and
      the adaptor protein Dab1. Dab1 is tyrosine phosphorylated by SFKs, and the
      kinases themselves can be further activated by phosphorylated Dab1. Increased
      Dab1 protein expression in fyn-deficient mice implies a response to impaired
      Reelin signaling that is also observed in mice lacking Reelin or its receptors.
      However, fyn deficiency alone does not compound the neuronal positioning defect
      of vldlr- or apoer2-deficient mice, and this finding suggests functional
      compensation by other SFKs. CONCLUSIONS: Our results show that Dab1 is a
      physiological substrate as well as an activator of SFKs in neurons. Based on
      genetic evidence gained from multiple strains of mutant mice with defects in
      Reelin signaling, we conclude that activation of SFKs is a normal part of the
      cellular Reelin response.

PMID- 12526742
TI  - Hox Gene Loss during Dynamic Evolution of the Nematode Cluster.
AB  - HOX GENES ARE IMPORTANT: their central role in anterior-posterior patterning
      provides a framework for molecular comparison of animal body plan evolution. The
      nematode Caenorhabditis elegans stands out as having a greatly reduced Hox gene
      complement. To address this, orthologs of C. elegans Hox genes were identified in
      six species from across the Nematoda, and they show that rapid homeodomain
      sequence evolution is a general feature of nematode Hox genes. Some nematodes
      express additional Hox genes belonging to orthology groups that are absent from
      C. elegans but present in other bilaterian animals. Analysis of the genomic
      environment of a newly identified Brugia malayi Hox6-8 ortholog (Bm-ant-1)
      revealed that it lay downstream of the Bm-egl-5 Hox gene and that their
      homeodomain exons are alternately cis spliced to the same 5' exon. This
      organization may represent an intermediate state in Hox gene loss via redundancy.
      The Hox clusters of nematodes are the product of a dynamic mix of gene loss and
      rapid sequence evolution, with the most derived state observed in the model C.
      elegans.

PMID- 12526743
TI  - Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer
      and eIF2C translation initiation factors.
AB  - RNA interference (RNAi) is the process of long, double-stranded (ds), RNA
      dependent posttranscriptional gene silencing (PTGS). In lower eukaryotes, dsRNA
      introduced into the cytoplasm is cleaved by the RNaseIII-like enzyme, Dicer, to
      21-23 nt RNA (short interfering [si] RNA), which may serve as guide for target
      mRNA degradation. In mammals, long-dsRNA-dependent PTGS is applicable only to a
      limited number of cell types, whereas siRNA synthesized in vitro is capable of
      effectively inducing gene silencing in a wide variety of cells. Although
      biochemical and genetic analyses in lower eukaryotes showed that Dicer and some
      PIWI family member proteins are essential for long-dsRNA-dependent PTGS, little
      is known about the molecular mechanisms underlying siRNA-based PTGS. Here, we
      show that Dicer and eIF2C translation initiation factors belonging to the PIWI
      family (eIF2C1-4) play an essential role in mammalian siRNA-mediated PTGS, most
      probably through synergistic interactions. Immunoprecipitation experiments
      suggest that, in human and mouse cells, complex formation occurs between Dicer
      and eIF2C1 or 2 and that the PIWI domain of eIF2C is essential for the formation
      of this complex.

PMID- 12526744
TI  - Caenorhabditis elegans innate immune response triggered by Salmonella enterica
      requires intact LPS and is mediated by a MAPK signaling pathway.
AB  - Compared to mammals, insects, and plants, relatively little is known about innate
      immune responses in the nematode Caenorhabditis elegans. Previous work showed
      that Salmonella enterica serovars cause a persistent infection in the C. elegans
      intestine that triggers gonadal programmed cell death (PCD) and that C. elegans
      cell death (ced) mutants are more susceptible to Salmonella-mediated killing. To
      further dissect the role of PCD in C. elegans innate immunity, we identified both
      C. elegans and S. enterica factors that affect the elicitation of Salmonella
      induced PCD. Salmonella-elicited PCD was shown to require the C. elegans homolog
      of the mammalian p38 mitogen-activated protein kinase (MAPK) encoded by the pmk-1
      gene. Inactivation of pmk-1 by RNAi blocked Salmonella-elicited PCD, and
      epistasis analysis showed that CED-9 lies downstream of PMK-1. Wild-type
      Salmonella lipopolysaccharide (LPS) was also shown to be required for the
      elicitation of PCD, as well as for persistence of Salmonella in the C. elegans
      intestine. However, a presumptive C. elegans TOLL signaling pathway did not
      appear to be required for the PCD response to Salmonella. These results establish
      a PMK-1-dependant PCD pathway as a C. elegans innate immune response to
      Salmonella.

PMID- 12526745
TI  - The contribution of E2F-regulated transcription to Drosophila PCNA gene function.
AB  - E2F proteins control cell cycle progression by predominantly acting as either
      activators or repressors of transcription. How the antagonizing activities of
      different E2Fs are integrated by cis-acting control regions into a final
      transcriptional output in an intact animal is not well understood. E2F function
      is required for normal development in many species, but it is not completely
      clear for which genes E2F-regulated transcription provides an essential
      biological function. To address these questions, we have characterized the
      control region of the Drosophila PCNA gene. A single E2F binding site within a
      100-bp enhancer is necessary and sufficient to direct the correct spatiotemporal
      program of G1-S-regulated PCNA expression during development. This dynamic
      program requires both E2F-mediated transcriptional activation and repression,
      which, in Drosophila, are thought to be carried out by two distinct E2F proteins.
      Our data suggest that functional antagonism between these different E2F proteins
      can occur in vivo by competition for the same binding site. An engineered PCNA
      gene with mutated E2F binding sites supports a low level of expression that can
      partially rescue the lethality of PCNA null mutants. Thus, E2F regulation of PCNA
      is dispensable for viability, but is nonetheless important for normal Drosophila
      development.

PMID- 12526746
TI  - The "Flash-Lag" effect occurs in audition and cross-modally.
AB  - In 1958 MacKay showed that a rigidly moving object becomes visually fragmented
      when part of it is continuously visible but the rest is illuminated
      intermittently. For example, the glowing tip of a lit cigarette moving under
      stroboscopic illumination appeared to move ahead of the intermittently lit body.
      Latterly rediscovered as "the flash-lag effect" (FLE), this illusion now is
      typically demonstrated on a computer monitor showing two spots of light, one
      translating across the screen and another briefly flashed in vertical alignment
      with it. Despite being physically aligned, the brief flash is seen to lag behind
      the moving spot. This effect has recently motivated much fruitful research,
      prompting a variety of potential explanations, including those based on motion
      extrapolation, differential latency, attention, postdiction, and temporal
      integration (for review, see ). With no consensus on which theory is most
      plausible, we have broadened the scope of enquiry to include audition and have
      found that the FLE is not confined to vision. Whether the auditory motion
      stimulus is a frequency sweep or a translating sound source, briefly presented
      auditory stimuli lag behind auditory movement. In addition, when we used spatial
      motion, we found that the FLE can occur cross-modally. Together, these findings
      challenge several FLE theories and point to a discrepancy between internal brain
      timing and external stimulus timing.

PMID- 12526747
TI  - Cleaner fish drives local fish diversity on coral reefs.
AB  - Coral reefs are one of the most diverse habitats in the world, yet our
      understanding of the processes affecting their biodiversity is limited. At the
      local scale, cleaner fish are thought to have a disproportionate effect, in
      relation to their abundance and size, on the activity of many other fish species,
      but confirmation of this species' effect on local fish diversity has proved
      elusive. The cleaner fish Labroides dimidiatus has major effects on fish activity
      patterns and may indirectly affect fish demography through the removal of large
      numbers of parasites. Here we show that small reefs where L. dimidiatus had been
      experimentally excluded for 18 months had half the species diversity of fish and
      one-fourth the abundance of individuals. Only fish that move among reefs,
      however, were affected. These fish include large species that themselves can
      affect other reef organisms. In contrast, the distribution of resident fish was
      not affected by cleaner fish. Thus, many fish appear to choose reefs based on the
      presence of cleaner fish. Our findings indicate that a single small and not very
      abundant fish has a strong influence on the movement patterns, habitat choice,
      activity, and local diversity and abundance of a wide variety of reef fish
      species.

PMID- 12526748
TI  - A new role for the transcriptional corepressor SIN3; regulation of centromeres.
AB  - Centromeres play a vital role in maintaining the genomic stability of eukaryotes
      by coordinating the equal distribution of chromosomes to daughter cells during
      mitosis and meiosis. Fission yeast (S. pombe) centromeres consist of a 4-9 kb
      central core region and 30-100 kb of flanking inner (imr/B) and outer (otr/K)
      repeats. These sequences direct a laminar kinetochore structure similar to that
      of human centromeres. Centromeric heterochromatin is generally underacetylated.
      We have previously shown that inhibition of histone deacetylases (HDACs) caused
      hyperacetylation of centromeres and defective chromosome segregation. SIN3 is a
      HDAC corepressor that has the ability to mediate HDAC targeting in the repression
      of promoters. In this study, we have characterized S. pombe sin three
      corepressors (Pst1p and Pst2p) to investigate whether SIN3-HDAC is required in
      the regulation of centromeres. We show that only pst1-1 and not pst2Delta cells
      displayed anaphase defects and thiabendazole sensitivity. pst1-1 cells showed
      reduced centromeric silencing, increased histone acetylation in centromeric
      chromatin, and defective centromeric sister chromatid cohesion. The HDAC Clr6p
      and Pst1p coimmunoprecipitated, and Pst1p colocalized with centromeres,
      particularly in binucleate cells. These data are consistent with a model in which
      Pst1p-Clr6p temporally associate with centromeres to carry out the initial
      deacetylation necessary for subsequent steps in heterochromatin formation.

PMID- 12526749
TI  - Ccd1, a novel protein with a DIX domain, is a positive regulator in the Wnt
      signaling during zebrafish neural patterning.
AB  - Wnt signaling plays a crucial role in directing cell differentiation, polarity,
      and growth. In the canonical pathway, Wnt receptors activate Dishevelled (Dvl),
      which then blocks the degradation of a key signal transducer, beta-catenin,
      leading to the nuclear accumulation of beta-catenin and induction of Wnt target
      genes through TCF/LEF family transcription factors. Here we identified a novel
      zebrafish gene encoding Ccd1, which possesses a DIX (Dishevelled-Axin) domain.
      DIX domains are essential for the signal transduction of two major Wnt downstream
      mediators, Dvl and Axin. Ccd1 formed homomeric and heteromeric complexes with Dvl
      and Axin and activated TCF-dependent transcription in vitro. In addition,
      overexpression of ccd1 in zebrafish embryos led to a reduction in the size of the
      eyes and forebrain (posteriorization), as seen with wnt8 overexpression, whereas
      a dominant-negative ccd1 (DN-ccd1) caused the opposite phenotype. Furthermore,
      the Wnt activation phenotype induced by ccd1 was inhibited by the expression of
      axin1 or DN-ccd1, and the wnt8 overexpression phenotype was rescued by DN-ccd1,
      suggesting that Ccd1 functions downstream of the Wnt receptor and upstream of
      Axin. These results indicate that Ccd1 is a novel positive regulator in this Wnt
      signaling pathway during zebrafish neural patterning.

PMID- 12526751
TI  - Chipping away at the old block.
AB  - With growing concern that women are still failing to progress in scientific
      careers, many countries are trying to address the problem. The British government
      has just received a hard-hitting report with recommendations for swift action to
      tackle the problems. Nigel Williams reports.

PMID- 12526750
TI  - EGF regulation of PITP dynamics is blocked by inhibitors of phospholipase C and
      of the Ras-MAP kinase pathway.
AB  - Phosphatidylinositol transfer proteins (PITP) function in signal transduction and
      in membrane traffic. Studies aimed at elucidating the mechanism of action of PITP
      have yielded a singular theme; the activity of PITP stems from its ability to
      transfer phosphatidylinositol (PI) from its site of synthesis to sites of
      cellular activity and to stimulate the local synthesis of phosphorylated forms of
      PI. The participation of various phosphoinositides in EGF signal transduction and
      in the trafficking of the EGF receptors is well documented. Using fluorescence
      lifetime imaging microscopy (FLIM) to measure fluorescence resonance energy
      transfer (FRET) between EGFP-PITP proteins and fluorescently labeled
      phospholipids, we report that PITPalpha and PITPbeta can dynamically interact
      with PI or PC at the plasma membrane when stimulated with EGF. Additionally,
      PITPbeta is localized at the Golgi, and EGF stimulation resulted in enhanced
      FRET. Inhibitors of the PLC and the Ras/MAP kinase pathway were both able to
      inhibit the EGF-stimulated interaction of PITPalpha with PI at the plasma
      membrane. The mobility of PITP proteins was determined by using fluorescence
      recovery after photobleaching (FRAP), and EGF stimulation reduced the mobility at
      the plasma membrane. We conclude that the dynamic behavior of PITPalpha and
      PITPbeta in vivo is a regulated process involving multiple mechanisms.

PMID- 12526752
TI  - Evolution and disease.
AB  - A recent meeting highlighted how much Darwinian thinking on natural selection
      illuminates the background to some major current human diseases and may offer
      insight into many more. Nigel Williams reports on a field seeking a place in
      mainstream medical education.

PMID- 12526754
TI  - Transgenerational epigenetic inheritance.

PMID- 12526755
TI  - Vertebrate development: taming the nodal waves.
AB  - Recent results have provided evidence that regulatory loops operating in
      vertebrate embryos between the developmental signalling factors Nodal and Lefty
      may provide a real example of the kind of reaction-diffusion process long
      predicted to be a mechanism of pattern formation.

PMID- 12526756
TI  - Visual perception: shaping what we see.
AB  - A new psychophysical study has examined the free flow of perception as observers
      viewed stimuli with several possible visual interpretations. The results suggest
      that our subjective impression of such ambiguous patterns may be more closely
      linked to the brain's encoding of complex shape than previously appreciated.

PMID- 12526757
TI  - Chromatin silencing: RNA in the driving seat.
AB  - Recent studies have provided major new insights into the mechanism by which
      eukaryotic organisms initiate heterochromatin formation. Surprisingly, RNA
      appears to be a central component of the chromatin silencing machinery.

PMID- 12526758
TI  - Bacterial division: the fellowship of the ring.
AB  - The Z ring, composed of the tubulin homolog FtsZ, is essential for bacterial cell
      division. Recently a new protein, ZapA, has been discovered that localizes to the
      Z ring and stabilizes it, probably by promoting the bundling of FtsZ
      protofilaments.

PMID- 12526759
TI  - Neurodegeneration: A non-apoptotic role for AIF in the brain.
AB  - A recent report provides new insights into the mechanisms of neurodegeneration.
      In a mouse mutant with progressive cerebellar and retinal degeneration, the
      expression of the apoptotic protein AIF was found to be downregulated leading
      paradoxically to apoptosis of neurons that is associated with an imbalance in
      free radical metabolism and cell cycle re-entry.

PMID- 12526760
TI  - Histone modifications: an assembly line for active chromatin?
AB  - Histone modifications play a major role in the control of genes in their natural
      chromatin context. A detailed, time-resolved analysis of histone modifications
      during gene activation has now revealed the order of appearance of particular
      histone modifications on a promoter during regulatory processes.

PMID- 12526761
TI  - Synapse formation: let's stick together.
AB  - Synapse formation requires the precise alignment and attachment of presynaptic
      and postsynaptic cells. Homophilic cell adhesion molecules have now been found to
      have a role in these processes on both sides of the synaptic cleft.

PMID- 12526762
TI  - DNA repair: bacteria join in.
AB  - In higher organisms, a major pathway for repairing double stranded breaks in DNA
      is non-homologous end-joining. Now a similar pathway has been shown to operate in
      bacterial cells, indicating that this important repair mechanism has been
      conserved through evolution.

PMID- 12526763
TI  - Periodic transcription: a cycle within a cycle.
AB  - Studies in model organisms indicate that one in every five genes may be subject
      to cell cycle regulated transcription. Moreover, a high proportion of
      periodically expressed genes have discrete roles in the cell division process,
      and their peaks of expression coincide with the interval during which they
      function. This periodic transcription is commonly regulated by transcription
      factors that are also periodically transcribed, and there is a growing number of
      examples where the transcription factors and their targets are conserved in yeast
      and mammalian cells. As such, it is worth considering why these regulatory
      circuits persist in such great number, how they are achieved and what role they
      may play in the cell cycle.

PMID- 12526764
TI  - The flip side of synapse elimination.
AB  - The fine tuning of synaptic circuits often requires an activity-dependent phase
      in which appropriate connections are strengthened and inappropriate connections
      are eliminated. In this issue of Neuron, Walsh and Lichtman propose a novel
      "synaptic takeover" mechanism for synapse elimination at the vertebrate NMJ,
      where withdrawal of one axon is accompanied by expansion of a competing axon into
      the newly vacated territory.

PMID- 12526765
TI  - Current compensation in neuronal homeostasis.
AB  - How do neurons maintain stable intrinsic properties over long periods of time as
      the channels that govern excitability turn over in the membrane? In this issue of
      Neuron, MacLean et al. argue that homeostatic regulation of intrinsic activity
      can occur by an activity-independent mechanism.

PMID- 12526766
TI  - From humble neural beginnings comes knowledge of numbers.
AB  - Following a recent report that monkey prefrontal cortex contains cells that
      represent number concepts, Nieder and Miller investigated the scale used to code
      numbers. In this issue of Neuron, they report that prefrontal cells use the same
      scale (Weber's Law) used by sensory neurons to code stimulus intensity,
      suggesting how abstract cognitive operations may arise from simpler building
      blocks that humans share with other animals.

PMID- 12526767
TI  - Pathways to Parkinsonism.
AB  - A novel gene for Parkinson's disease (PD), DJ-1, has been identified that encodes
      a multifunctional product with several known protein-protein interactions and
      effects on gene expression. Here, I outline how it is possible to construct
      hypotheses that place DJ-1 in different relationships to the other known PD
      genes, alpha-synuclein and parkin. The identification of multiple genetic causes
      will provide further impetus to describe the pathway leading to PD.

PMID- 12526768
TI  - Diversifying neural cells through order of birth and asymmetry of division.
AB  - A key question in developmental neurobiology is how the diversity of cell types
      that make up the mature nervous system are generated from a common set of
      progenitor cells. Drosophila genes governing temporal cell fate determination and
      asymmetric cell divisions involving numb may represent evolutionarily conserved
      mechanisms for regulating cell fate diversification in the developing nervous
      system.

PMID- 12526769
TI  - Fireworks in the primate retina: in vitro photodynamics reveals diverse LGN
      projecting ganglion cell types.
AB  - Diverse cell types and parallel pathways are characteristic of the vertebrate
      nervous system, yet it remains a challenge to define the basic components of most
      neural structures. We describe a process termed retrograde photodynamics that
      allowed us to rapidly make the link between morphology, physiology, and
      connectivity for ganglion cells in the macaque retina that project to the lateral
      geniculate nucleus (LGN). Rhodamine dextran injected into the LGN was transported
      retrogradely and sequestered within the cytoplasm of ganglion cell bodies.
      Exposure of the retina to light in vitro liberated the tracer and allowed it to
      diffuse throughout the dendrites, revealing the cell's complete morphology. Eight
      previously unknown LGN-projecting cell types were identified. Cells could also be
      targeted in vitro for intracellular recording and physiological analysis. The
      photodynamic process was also observed in pyramidal cells in a rat neocortical
      slice.

PMID- 12526770
TI  - Colonic epithelial expression of ErbB2 is required for postnatal maintenance of
      the enteric nervous system.
AB  - We utilized the Cre-LoxP system to establish erbB2 conditional mutant mice in
      order to investigate the role of erbB2 in postnatal development of the enteric
      nervous system. The erbB2/nestin-Cre conditional mutants exhibit retarded growth,
      distended colons, and premature death, resembling human Hirschsprung's disease.
      Enteric neurons and glia are present at birth in the colon of erbB2/nestin-Cre
      mutants; however, a marked loss of multiple classes of enteric neurons and glia
      occurs by 3 weeks of age. Furthermore, we demonstrate that the requirement for
      erbB2 in maintaining the enteric nervous system is not cell autonomous, but
      rather erbB2 signaling in the colonic epithelia is required for the postnatal
      survival of enteric neurons and glia.

PMID- 12526771
TI  - Genetic specification of axonal arbors: atonal regulates robo3 to position
      terminal branches in the Drosophila nervous system.
AB  - Drosophila sensory neurons form distinctive terminal branch patterns in the
      developing neuropile of the embryonic central nervous system. In this paper we
      make a genetic analysis of factors regulating arbor position. We show that
      mediolateral position is determined in a binary fashion by expression
      (chordotonal neurons) or nonexpression (multidendritic neurons) of the Robo3
      receptor for the midline repellent Slit. Robo3 expression is one of a suite of
      chordotonal neuron properties that depend on expression of the proneural gene
      atonal. Different features of terminal branches are separately regulated: an
      arbor can be shifted mediolaterally without affecting its dorsoventral location,
      and the distinctive remodeling of one arbor continues as normal despite this
      arbor shifting to an abnormal position in the neuropile.

PMID- 12526772
TI  - The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through
      enabled and, in parallel, Rac and UNC-115/AbLIM.
AB  - Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To
      characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule,
      MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and
      excessive axon and cell body outgrowth. These defects are suppressed by loss-of
      function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc
      115 (a putative actin binding protein). ced-10, unc-34, and unc-115 also function
      in endogenous unc-40 signaling. Our results indicate that Enabled functions in
      axonal attraction as well as axon repulsion. UNC-40 has two conserved cytoplasmic
      motifs that mediate distinct downstream pathways: CED-10, UNC-115, and the UNC-40
      P2 motif act in one pathway, and UNC-34 and the UNC-40 P1 motif act in the other.
      Thus, UNC-40 might act as a scaffold to deliver several independent signals to
      the actin cytoskeleton.

PMID- 12526773
TI  - In vivo time-lapse imaging of synaptic takeover associated with naturally
      occurring synapse elimination.
AB  - During development, competition between axons causes permanent removal of
      synaptic connections, but the dynamics have not been directly observed. Using
      transgenic mice that express two spectral variants of fluorescent proteins in
      motor axons, we imaged competing axons at developing neuromuscular junctions in
      vivo. Typically, one axon withdrew progressively from postsynaptic sites and the
      competing axon extended axonal processes to occupy those sites. In rare instances
      when the remaining axon did not reoccupy a site, the postsynaptic receptors
      rapidly disappeared. Interestingly, the progress and outcome of competition was
      unpredictable. Moreover, the relative areas occupied by the competitors shifted
      in favor of one axon and then the other. These results show synaptic competition
      is not always monotonic and that one axon's contraction in synaptic area is
      associated with another axon's expansion.

PMID- 12526774
TI  - Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade.
AB  - Acid-sensing ion channels (ASICs) open when extracellular pH drops and they are
      enhanced by lactate, making them specialized for detecting lactic acidosis.
      Highly expressed on cardiac nociceptors and some other sensory neurons, ASICs may
      help trigger pain caused by tissue ischemia. We report that H(+) opens ASIC3 by
      speeding release of Ca(2+) from a high-affinity binding site (K(Ca) = 150 nM) on
      the extracellular side of the pore. The bound Ca(2+) blocks permeation and the
      channel conducts when multiple H(+) ions relieve this block. Activation through
      Ca(2+) explains sensitivity to lactate, which decreases extracellular [Ca(2+)],
      and it may prove relevant in CNS pathologies (stroke, seizure) that
      simultaneously drop pH and Ca(2+).

PMID- 12526775
TI  - A fluorometric approach to local electric field measurements in a voltage-gated
      ion channel.
AB  - Site-specific electrostatic measurements have been limited to soluble proteins
      purified for in vitro spectroscopic characterization or proteins of known
      structure; however, comparable measurements have not been made for functional
      membrane bound proteins. Here, using an electrochromic fluorophore, we describe a
      method to monitor localized electric field changes in a voltage-gated potassium
      channel. By coupling the novel probe Di-1-ANEPIA to cysteines in Shaker and
      tracking field-induced optical changes, in vivo electrostatic measurements were
      recorded with submillisecond resolution. This technique reports dynamic changes
      in the electric field during the gating process and elucidates the electric field
      profile within Shaker. The extension of this method to other membrane bound
      proteins, including transporters, will yield insight into the role of electrical
      forces on protein function.

PMID- 12526776
TI  - Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers
      fast exocytosis without stimulating SNARE interactions.
AB  - Sr(2+) triggers neurotransmitter release similar to Ca(2+), but less efficiently.
      We now show that in synaptotagmin 1 knockout mice, the fast component of both
      Ca(2+)- and Sr(2+)-induced release is selectively impaired, suggesting that both
      cations partly act by binding to synaptotagmin 1. Both the C(2)A and the C(2)B
      domain of synaptotagmin 1 bind Ca(2+) in phospholipid complexes, but only the
      C(2)B domain forms Sr(2+)/phospholipid complexes; therefore, Sr(2+) binding to
      the C(2)B domain is sufficient to trigger fast release, although with decreased
      efficacy. Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE
      proteins, whereas Sr(2+) even at high concentrations does not. Thus, triggering
      of the fast component of release by Sr(2+) as a Ca(2+) agonist involves the
      formation of synaptotagmin/phospholipid complexes, but does not require
      stimulated SNARE binding.

PMID- 12526777
TI  - Activity-independent homeostasis in rhythmically active neurons.
AB  - The shal gene encodes the transient potassium current (I(A)) in neurons of the
      lobster stomatogastric ganglion. Overexpression of Shal by RNA injection into
      neurons produces a large increase in I(A), but surprisingly little change in the
      neuron's firing properties. Accompanying the increase in I(A) is a dramatic and
      linearly correlated increase in the hyperpolarization-activated inward current
      (I(h)). The enhanced I(h) electrophysiologically compensates for the enhanced
      I(A), since pharmacological blockade of I(h) uncovers the physiological effects
      of the increased I(A). Expression of a nonfunctional mutant Shal also induces a
      large increase in I(h), demonstrating a novel activity-independent coupling
      between the Shal protein and I(h) enhancement. Since I(A) and I(h) influence
      neuronal activity in opposite directions, our results suggest a selective
      coregulation of these channels as a mechanism for constraining cell activity
      within appropriate physiological parameters.

PMID- 12526778
TI  - Activation of delta opioid receptors induces receptor insertion and neuropeptide
      secretion.
AB  - Here we describe a novel mechanism for plasma membrane insertion of the delta
      opioid receptor (DOR). In small dorsal root ganglion neurons, only low levels of
      DORs are present on the cell surface, in contrast to high levels of intracellular
      DORs mainly associated with vesicles containing calcitonin gene-related peptide
      (CGRP). Activation of surface DORs caused Ca(2+) release from IP(3)-sensitive
      stores and Ca(2+) entry, resulting in a slow and long-lasting exocytosis, DOR
      insertion, and CGRP release. In contrast, membrane depolarization or activation
      of vanilloid and P2Y(1) receptors induced a rapid DOR insertion. Thus, DOR
      activation induces a Ca(2+)-dependent insertion of DORs that is coupled to a
      release of excitatory neuropeptides, suggesting that treatment of inflammatory
      pain should include blockade of DORs.

PMID- 12526780
TI  - Coding of cognitive magnitude: compressed scaling of numerical information in the
      primate prefrontal cortex.
AB  - Whether cognitive representations are better conceived as language-based,
      symbolic representations or perceptually related, analog representations is a
      subject of debate. If cognitive processes parallel perceptual processes, then
      fundamental psychophysical laws should hold for each. To test this, we analyzed
      both behavioral and neuronal representations of numerosity in the prefrontal
      cortex of rhesus monkeys. The data were best described by a nonlinearly
      compressed scaling of numerical information, as postulated by the Weber-Fechner
      law or Stevens' law for psychophysical/sensory magnitudes. This nonlinear
      compression was observed on the neural level during the acquisition phase of the
      task and maintained through the memory phase with no further compression. These
      results suggest that certain cognitive and perceptual/sensory representations
      share the same fundamental mechanisms and neural coding schemes.

PMID- 12526779
TI  - Activity-dependent presynaptic facilitation and hebbian LTP are both required and
      interact during classical conditioning in Aplysia.
AB  - Using a simplified preparation of the Aplysia siphon-withdrawal reflex, we
      previously found that associative plasticity at synapses between sensory neurons
      and motor neurons contributes importantly to classical conditioning of the
      reflex. We have now tested the roles in that plasticity of two associative
      cellular mechanisms: activity-dependent enhancement of presynaptic facilitation
      and postsynaptically induced long-term potentiation. By perturbing molecular
      signaling pathways in individual neurons, we have provided the most direct
      evidence to date that each of these mechanisms contributes to behavioral
      learning. In addition, our results suggest that the two mechanisms are not
      independent but rather interact through retrograde signaling.

PMID- 12526781
TI  - Early setting of grammatical processing in the bilingual brain.
AB  - The existence of a "critical period" for language acquisition is controversial.
      Bilingual subjects with variable age of acquisition (AOA) and proficiency level
      (PL) constitute a suitable model to study this issue. We used functional magnetic
      resonance imaging to investigate the effects of AOA and PL on neural correlates
      of grammatical and semantic judgments in Italian-German bilinguals who learned
      the second language at different ages and had different proficiency levels. While
      the pattern of brain activity for semantic judgment was largely dependent on PL,
      AOA mainly affected the cortical representation of grammatical processes. These
      findings support the view that both AOA and PL affect the neural substrates of
      second language processing, with a differential effect on grammar and semantics.

PMID- 12526782
TI  - Recognition memory and the human hippocampus.
AB  - The capacity for declarative memory depends on the hippocampal region and
      adjacent cortex within the medial temporal lobe. One of the most widely studied
      examples of declarative memory is the capacity to recognize recently encountered
      material as familiar, but uncertainty remains about whether intact recognition
      memory depends on the hippocampal region itself and, if so, what the nature of
      the hippocampal contribution might be. Seven patients with bilateral damage
      thought to be limited primarily to the hippocampal region were impaired on three
      standard tests of recognition memory. In addition, the patients were impaired to
      a similar extent at Remembering and Knowing, measures of the two processes
      thought to support recognition performance: the ability to remember the learning
      episode (episodic recollection) and the capacity for judging items as familiar
      (familiarity).

PMID- 12526785
TI  - Parc-ing p53 in the cytoplasm.
AB  - Nikolaev et al. (this issue of Cell) report the identification of a parkin-like
      protein, Parc, and its role in anchoring the tumor suppressor protein p53 in the
      cytoplasm reveals yet another level of control of p53 function. Regulation of the
      subcellular localization of p53 by Parc may serve as a novel target in treatment
      of certain types of tumors.

PMID- 12526786
TI  - Toxin-antitoxin pairs in bacteria: killers or stress regulators?
AB  - Plasmid toxin-antitoxin systems, which kill daughter cells that fail to inherit
      the plasmid genome, have chromosomal homologs in eubacteria and archaea. In this
      issue of Cell, Pederson et al. show that the E. coli RelE toxin cleaves mRNA in
      the ribosomal A site, potentially allowing it to function as a stress regulator
      during amino acid starvation.

PMID- 12526787
TI  - Pars, PI 3-kinase, and the establishment of neuronal polarity.
AB  - As reported in this issue of Cell, the protein complex consisting of mPar3,
      mPar6, and atypical protein kinase C is selectively localized to the axonal
      growth cone of cultured hippocampal neurons and is required for specification of
      the axon.

PMID- 12526788
TI  - DNA single-strand break repair and spinocerebellar ataxia.
AB  - DNA single-strand break repair (SSBR) is critical for the survival and genetic
      stability of mammalian cells. Three papers have recently associated mutations in
      putative human SSBR genes with hereditary spinocerebellar ataxia. The emerging
      links between SSBR and neurodegenerative disorders are discussed.

PMID- 12526789
TI  - Regulating the regulators: lysine modifications make their mark.
AB  - Decades of research have uncovered much of the molecular machinery responsible
      for establishing and maintaining proper gene transcription patterns in
      eukaryotes. Although the composition of this machinery is largely known,
      mechanisms regulating its activity by covalent modification are just coming into
      focus. Here, we review several cases of ubiquitination, sumoylation, and
      acetylation that link specific covalent modification of the transcriptional
      apparatus to their regulatory function. We propose that potential cascades of
      modifications serve as molecular rheostats that fine-tune the control of
      transcription in diverse organisms.

PMID- 12526790
TI  - Tube morphogenesis: making and shaping biological tubes.
AB  - Many organs are composed of epithelial tubes that transport vital fluids. Such
      tubular organs develop in many different ways and generate tubes of widely
      varying sizes and structures, but always with the apical epithelial surface
      lining the lumen. We describe recent progress in several diverse cell culture and
      genetic models of tube morphogenesis, which suggest apical membrane biogenesis,
      vesicle fusion, and secretion play central roles in tube formation and growth. We
      propose a unifying mechanism of tube morphogenesis that has been modified to
      create tube diversity and describe how defects in the tube size-sensing step can
      lead to polycystic kidney disease.

PMID- 12526791
TI  - Parc: a cytoplasmic anchor for p53.
AB  - Nuclear localization of p53 is essential for its tumor suppressor function. Here,
      we have identified Parc, a Parkin-like ubiquitin ligase, as a cytoplasmic anchor
      protein in p53-associated protein complexes. Parc directly interacts and forms a
      approximately 1 MDa complex with p53 in the cytoplasm of unstressed cells. In the
      absence of stress, inactivation of Parc induces nuclear localization of
      endogenous p53 and activates p53-dependent apoptosis. Overexpression of Parc
      promotes cytoplasmic sequestration of ectopic p53. Furthermore, abnormal
      cytoplasmic localization of p53 was observed in a number of neuroblastoma cell
      lines; RNAi-mediated reduction of endogenous Parc significantly sensitizes these
      neuroblastoma cells in the DNA damage response. These results reveal that Parc is
      a critical regulator in controlling p53 subcellular localization and subsequent
      function.

PMID- 12526792
TI  - Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial
      import receptor Tom70.
AB  - The role of cytosolic factors in protein targeting to mitochondria is poorly
      understood. Here, we show that in mammals, the cytosolic chaperones Hsp90 and
      Hsp70 dock onto a specialized TPR domain in the import receptor Tom70 at the
      outer mitochondrial membrane. This interaction serves to deliver a set of
      preproteins to the receptor for subsequent membrane translocation dependent on
      the Hsp90 ATPase. Disruption of the chaperone/Tom70 recognition inhibits the
      import of these preproteins into mitochondria. In yeast, Hsp70 rather than Hsp90
      is used in import, and Hsp70 docking is required for the formation of a
      productive preprotein/Tom70 complex. We outline a novel mechanism in which
      chaperones are recruited for a specific targeting event by a membrane-bound
      receptor.

PMID- 12526793
TI  - Apical complex genes control mitotic spindle geometry and relative size of
      daughter cells in Drosophila neuroblast and pI asymmetric divisions.
AB  - Drosophila neuroblast asymmetric divisions generate two daughters of unequal size
      and fate. A complex of apically localized molecules mediates basal localization
      of cell fate determinants and apicobasal orientation of the mitotic spindle, but
      how daughter cell size is controlled remains unclear. Here we show that mitotic
      spindle geometry and unequal daughter cell size are controlled by two parallel
      pathways (Bazooka/DaPKC and Pins/G alpha i) within the apical complex. While the
      localized activity of either pathway alone is sufficient to mediate the
      generation of an asymmetric mitotic spindle and unequal size neuroblast
      daughters, loss of both pathways results in symmetric divisions. In sensory organ
      precursors, Bazooka/DaPKC and Pins/G alpha i localize to opposite sides of the
      cortex and function in opposition to generate a symmetric spindle.

PMID- 12526794
TI  - Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI
      3-kinase activity.
AB  - How a neuron becomes polarized remains an outstanding question. Here, we report
      that selection of the future axon among neurites of a cultured hippocampal neuron
      requires the activity of growth factor receptor tyrosine kinase,
      phosphatidylinositol 3-kinase (PI 3-kinase), as well as atypical protein kinase C
      (aPKC). The PI 3-kinase activity, highly localized to the tip of the newly
      specified axon of stage 3 neurons, is essential for the proper subcellular
      localization of mPar3, the mammalian homolog of C. elegans polarity protein Par3.
      Polarized distribution of not only mPar3 but also mPar6 is important for axon
      formation; ectopic expression of mPar6 or mPar3, or just the N terminus of mPar3,
      leaves neurons with no axon specified. Thus, neuronal polarity is likely to be
      controlled by the mPar3/mPar6/aPKC complex and the PI 3-kinase signaling pathway,
      both serving evolutionarily conserved roles in specifying cell polarity.

PMID- 12526795
TI  - A stimulatory role for cGMP-dependent protein kinase in platelet activation.
AB  - It is currently accepted that cGMP-dependent protein kinase (PKG) inhibits
      platelet activation. Here, we show that PKG plays an important stimulatory role
      in platelet activation. Expression of recombinant PKG in a reconstituted cell
      model enhanced von Willebrand factor (vWF)-induced activation of the platelet
      integrin alpha(IIb)beta(3). PKG knockout mice showed impaired platelet responses
      to vWF or low doses of thrombin and prolonged bleeding time. Human platelet
      aggregation induced by vWF or low-dose thrombin was inhibited by PKG inhibitors
      but enhanced by cGMP. Furthermore, a cGMP-enhancing agent, sildenafil, promoted
      vWF- or thrombin-induced platelet aggregation. The cGMP-stimulated platelet
      responses are biphasic, consisting of an initial transient stimulatory response
      that promotes platelet aggregation and a subsequent inhibitory response that
      limits the size of thrombi.

PMID- 12526796
TI  - The clearance mechanism of chilled blood platelets.
AB  - Platelet transfusion is a very common lifesaving medical procedure. Not widely
      known is the fact that platelets, unlike other blood cells, rapidly leave the
      circulation if refrigerated prior to transfusion. This peculiarity requires blood
      services to store platelets at room temperature, limiting platelet supplies for
      clinical needs. Here, we describe the mechanism of this clearance system, a
      longstanding mystery. Chilling platelets clusters their von Willebrand (vWf)
      receptors, eliciting recognition of mouse and human platelets by hepatic
      macrophage complement type 3 (CR3) receptors. CR3-expressing but not CR3
      deficient mice exposed to cold rapidly decrease platelet counts. Cooling primes
      platelets for activation. We propose that platelets are thermosensors, primed at
      peripheral sites where most injuries occurred throughout evolution. Clearance
      prevents pathologic thrombosis by primed platelets. Chilled platelets bind vWf
      and function normally in vitro and ex vivo after transfusion into CR3-deficient
      mice. Therefore, GPIb modification might permit cold platelet storage.

PMID- 12526798
TI  - Crystal structure of carnitine acetyltransferase and implications for the
      catalytic mechanism and fatty acid transport.
AB  - Carnitine acyltransferases have crucial roles in the transport of fatty acids for
      beta-oxidation. Dysregulation of these enzymes can lead to serious diseases in
      humans, and they are targets for therapeutic development against diabetes. We
      report the crystal structures of murine carnitine acetyltransferase (CRAT), alone
      and in complex with its substrate carnitine or CoA. The structure contains two
      domains. Surprisingly, these two domains share the same backbone fold, which is
      also similar to that of chloramphenicol acetyltransferase and dihydrolipoyl
      transacetylase. The active site is located at the interface between the two
      domains. Carnitine and CoA are bound in deep channels in the enzyme, on opposite
      sides of the catalytic His343 residue. The structural information provides a
      molecular basis for understanding the catalysis by carnitine acyltransferases and
      for designing their inhibitors. Specifically, our structural information suggests
      that the substrate carnitine may assist the catalysis by stabilizing the oxyanion
      in the reaction intermediate.

PMID- 12526797
TI  - Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape
      shifting pathway for integrin regulation.
AB  - The structure of the I domain of integrin alpha L beta 2 bound to the Ig
      superfamily ligand ICAM-1 reveals the open ligand binding conformation and the
      first example of an integrin-IgSF interface. The I domain Mg2+ directly
      coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241
      enables a critical salt bridge. Liganded and unliganded structures for both high-
      and intermediate-affinity mutant I domains reveal that ligand binding can induce
      conformational change in the alpha L I domain and that allosteric signals can
      convert the closed conformation to intermediate or open conformations without
      ligand binding. Pulling down on the C-terminal alpha 7 helix with introduced
      disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions
      in the closed, intermediate, and open conformations, with a progressive increase
      in affinity.

PMID- 12526799
TI  - Entrapping ribosomes for viral translation: tRNA mimicry as a molecular Trojan
      horse.
AB  - Turnip yellow mosaic virus (TYMV) has a genomic plus-strand RNA with a 5' cap
      followed by overlapping and different reading frames for the movement protein and
      polyprotein, while the distal coat protein cistron is translated from a
      subgenomic RNA. The 3'-untranslated region harbors a tRNA-like structure (TLS) to
      which a valine moiety can be added and it is indispensable for virus viability.
      Here, we report about a surprising interaction between TYMV-RNA-programmed
      ribosomes and 3'-valylated TLS that yields polyprotein with the valine N
      terminally incorporated by a translation mechanism resistant to regular
      initiation inhibitors. Disruption of the TLS exclusively abolishes polyprotein
      synthesis, which can be restored by adding excess TLS in trans. Our observations
      imply a novel eukaryotic mechanism for internal initiation of mRNA translation.

PMID- 12526801
TI  - Accolade for elegans.

PMID- 12526800
TI  - The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the
      ribosomal A site.
AB  - The Escherichia coli relBE operon encodes a toxin-antitoxin pair, RelE-RelB. RelB
      can reverse inhibition of protein synthesis by RelE in vivo. We have found that
      although RelE does not degrade free RNA, it cleaves mRNA in the ribosomal A site
      with high codon specificity. Among stop codons UAG is cleaved with fast, UAA
      intermediate and UGA slow rate, while UCG and CAG are cleaved most rapidly among
      sense codons. We suggest that inhibition of protein synthesis by RelE is reversed
      with the help of tmRNA, and that RelE plays a regulatory role in bacteria during
      adaptation to poor growth conditions.

PMID- 12526802
TI  - Shifty ciliates: frequent programmed translational frameshifting in euplotids.
AB  - Recent work suggests that there is a high frequency of programmed +1
      translational frameshifting in ciliates of the Euplotes genus. Frequent
      frameshifting may have been potentiated by stop codon reassignment, which is also
      a feature of this group.

PMID- 12526803
TI  - Controlling calcium entry.
AB  - Ca(2+) enters cells through an assortment of Ca(2+)-permeable channels that
      respond to different stimuli and couple to different cellular responses. Several
      different Ca(2+) entry pathways can be activated by receptors that stimulate
      phospholipase C (PLC). Both limbs of this signaling pathway (IP(3) and
      diacylglycerol), PLC itself, and its substrate (PIP(2)) contribute to the
      coordinate regulation of these Ca(2+) entry pathways.

PMID- 12526804
TI  - Signaling network model of chromatin.
AB  - We suggest that common principles underlie both cellular signaling networks and
      chromatin. To exemplify similarities, we focus on signaling complexes that form
      at membrane receptors and on nucleosomes. Multiple signal-transducing
      modifications on side chain residues of receptor tyrosine kinases (RTKs) and
      histone proteins are used to create docking sites that facilitate proximal
      relations of enzymes and their substrates. We argue that multiple histone
      modifications, like RTK modifications, promote switch-like behavior and ensure
      robustness of the signal, and we compare this interpretation with the histone
      code hypothesis. This view provides insight into chromatin function and
      epigenetic inheritance.

PMID- 12526805
TI  - ATR regulates fragile site stability.
AB  - Conditions that partially inhibit DNA replication induce expression of common
      fragile sites. These sites form gaps and breaks on metaphase chromosomes and are
      deleted and rearranged in many tumors. Yet, the mechanism of fragile site
      expression has been elusive. We demonstrate that the replication checkpoint
      kinase ATR, but not ATM, is critical for maintenance of fragile site stability.
      ATR deficiency results in fragile site expression with and without addition of
      replication inhibitors. Thus, we propose that fragile sites are unreplicated
      chromosomal regions resulting from stalled forks that escape the ATR replication
      checkpoint. These findings have important implications for understanding both the
      mechanism of fragile site instability and the consequences of stalled replication
      in mammalian cells.

PMID- 12526806
TI  - Physical and functional interactions among basic chromosome organizational
      features govern early steps of meiotic chiasma formation.
AB  - Analysis of meiotic recombination by functional genomic approaches reveals
      prominent spatial and functional interactions among diverse organizational
      determinants. Recombination occurs between chromatin loop sequences; however,
      these sequences are spatially tethered to underlying chromosome axes via their
      recombinosomes. Meiotic chromosomal protein, Red1, localizes to chromosome axes;
      however, Red1 loading is modulated by R/G-bands isochores and thus by bulk
      chromatin state. Recombination is also modulated by isochore determinants: R
      bands differentially favor double-strand break (DSB) formation but disfavor
      subsequent loading of meiotic RecA homolog, Dmc1. Red1 promotes DSB formation in
      both R- and G-bands and then promotes Dmc1 loading, specifically counteracting
      disfavoring R-band effects. These complexities are discussed in the context of
      chiasma formation as a series of coordinated local changes at the DNA and
      chromosome-axis levels.

PMID- 12526807
TI  - ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA
      glycosylase/lyase.
AB  - Mutations in the Arabidopsis ROS1 locus cause transcriptional silencing of a
      transgene and a homologous endogenous gene. In the ros1 mutants, the promoter of
      the silenced loci is hypermethylated, which may be triggered by small RNAs
      produced from the transgene repeats. The transcriptional silencing in ros1
      mutants can be released by the ddm1 mutation or the application of the DNA
      methylation inhibitor 5-aza-2'-deoxycytidine. ROS1 encodes an endonuclease III
      domain nuclear protein with bifunctional DNA glycosylase/lyase activity against
      methylated but not unmethylated DNA. The ros1 mutant shows enhanced sensitivity
      to genotoxic agents methyl methanesulfonate and hydrogen peroxide. We suggest
      that ROS1 is a DNA repair protein that represses homology-dependent
      transcriptional gene silencing by demethylating the target promoter DNA.

PMID- 12526808
TI  - Crystal structures of the Bacillus stearothermophilus CCA-adding enzyme and its
      complexes with ATP or CTP.
AB  - CCA-adding enzymes polymerize CCA onto the 3' terminus of immature tRNAs without
      using a nucleic acid template. The 3.0 A resolution crystal structures of the CCA
      adding enzyme from Bacillus stearothermophilus and its complexes with ATP or CTP
      reveal a seahorse-shaped subunit consisting of four domains: head, neck, body,
      and tail. The head is structurally homologous to the palm domain of DNA
      polymerase beta but has additional structural features and functions. The neck,
      body, and tail represent new protein folding motifs. The neck provides a specific
      template for the incoming ATP or CTP, whereas the body and tail may bind tRNA.
      Each subunit has one active site capable of switching its base specificity
      between ATP and CTP, an important component of the CCA-adding mechanism.

PMID- 12526809
TI  - Structure of internalin, a major invasion protein of Listeria monocytogenes, in
      complex with its human receptor E-cadherin.
AB  - Listeria monocytogenes, a food-borne bacterial pathogen, enters mammalian cells
      by inducing its own phagocytosis. The listerial protein internalin (InlA)
      mediates bacterial adhesion and invasion of epithelial cells in the human
      intestine through specific interaction with its host cell receptor E-cadherin. We
      present the crystal structures of the functional domain of InlA alone and in a
      complex with the extracellular, N-terminal domain of human E-cadherin (hEC1). The
      leucine rich repeat (LRR) domain of InlA surrounds and specifically recognizes
      hEC1. Individual interactions were probed by mutagenesis and analytical
      ultracentrifugation. These include Pro16 of hEC1, a major determinant for human
      susceptibility to L. monocytogenes infection that is essential for intermolecular
      recognition. Our studies reveal the structural basis for host tro-pism of this
      bacterium and the molecular deception L. monocytogenes employs to exploit the E
      cadherin system.

PMID- 12526810
TI  - Molecular and functional profiling of memory CD8 T cell differentiation.
AB  - How and when memory T cells form during an immune response are long-standing
      questions. To better understand memory CD8 T cell development, a time course of
      gene expression and functional changes in antigen-specific T cells during viral
      infection was evaluated. The expression of many genes continued to change after
      viral clearance in accordance with changes in CD8 T cell functional properties.
      Even though memory cell precursors were present at the peak of the immune
      response, these cells did not display hallmark functional traits of memory T
      cells. However, these cells gradually acquired the memory cell qualities of self
      renewal and rapid recall to antigen suggesting the model that antigen-specific
      CD8 T cells progressively differentiate into memory cells following viral
      infection.

PMID- 12526811
TI  - HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic
      pathway.
AB  - The HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the
      trans-Golgi network (TGN) enables HIV-1 to escape immune surveillance. However,
      the cellular pathway used by Nef to downregulate MHC-I is unknown. Here, we show
      that Nef and PACS-1 combine to usurp the ARF6 endocytic pathway by a PI3K
      dependent process and downregulate cell surface MHC-I to the TGN. This mechanism
      requires the hierarchical actions of three Nef motifs-the acidic cluster
      62EEEE(65), the SH3 domain binding site 72PXXP(75), and M(20)-in controlling PACS
      1-dependent sorting to the TGN, ARF6 activation, and sequestering internalized
      MHC-I to the TGN, respectively. These data provide new insights into the cellular
      basis of HIV-1 immunoevasion.

PMID- 12526812
TI  - Conversion of proepithelin to epithelins: roles of SLPI and elastase in host
      defense and wound repair.
AB  - Increased leukocyte elastase activity in mice lacking secretory leukocyte
      protease inhibitor (SLPI) leads to impaired wound healing due to enhanced
      activity of TGFbeta and perhaps additional mechanisms. Proepithelin (PEPI), an
      epithelial growth factor, can be converted to epithelins (EPIs) in vivo by
      unknown mechanisms with unknown consequences. We found that PEPI and EPIs exert
      opposing activities. EPIs inhibit the growth of epithelial cells but induce them
      to secrete the neutrophil attractant IL-8, while PEPI blocks neutrophil
      activation by tumor necrosis factor, preventing release of oxidants and
      proteases. SLPI and PEPI form complexes, preventing elastase from converting PEPI
      to EPIs. Supplying PEPI corrects the wound-healing defect in SLPI null mice.
      Thus, SLPI/elastase act via PEPI/EPIs to operate a switch at the interface
      between innate immunity and wound healing.

PMID- 12526813
TI  - Epithelial tube morphology is determined by the polarized growth and delivery of
      apical membrane.
AB  - Formation of tubes of the correct size and shape is essential for viability of
      most organisms, yet little is understood of the mechanisms controlling tube
      morphology. We identified a new allele of hairy in a mutagenesis screen and
      showed that hairy mutations cause branching and bulging of the normally
      unbranched salivary tube, in part through prolonged expression of huckebein
      (hkb). HKB controls polarized cell shape change and apical membrane growth during
      salivary cell invagination via two downstream target genes, crumbs (crb), a
      determinant of the apical membrane, and klarsicht (klar), which mediates
      microtubule-dependent organelle transport. In invaginating salivary cells, crb
      and klar mediate growth and delivery of apical membrane, respectively, thus
      regulating the size and shape of the salivary tube.

PMID- 12526814
TI  - Regulation of notch signaling by o-linked fucose.
AB  - Notch and its ligands are modified by a protein O-fucosyltransferase (OFUT1) that
      attaches fucose to a Serine or Threonine within EGF domains. By using RNAi to
      decrease Ofut1 expression in Drosophila, we demonstrate that O-linked fucose is
      positively required for Notch signaling, including both Fringe-dependent and
      Fringe-independent processes. The requirement for Ofut1 is cell autonomous, in
      the signal-receiving cell, and upstream of Notch activation. The transcription of
      Ofut1 is developmentally regulated, and surprisingly, overexpression of Ofut1
      inhibits Notch signaling. Together, these results indicate that OFUT1 is a core
      component of the Notch pathway, which is required for the activation of Notch by
      its ligands, and whose regulation may contribute to the pattern of Notch
      activation during development.

PMID- 12526815
TI  - Identification of a signaling network in lateral nucleus of amygdala important
      for inhibiting memory specifically related to learned fear.
AB  - We identified the Grp gene, encoding gastrin-releasing peptide, as being highly
      expressed both in the lateral nucleus of the amygdala, the nucleus where
      associations for Pavlovian learned fear are formed, and in the regions that
      convey fearful auditory information to the lateral nucleus. Moreover, we found
      that GRP receptor (GRPR) is expressed in GABAergic interneurons of the lateral
      nucleus. GRP excites these interneurons and increases their inhibition of
      principal neurons. GRPR-deficient mice showed decreased inhibition of principal
      neurons by the interneurons, enhanced long-term potentiation (LTP), and greater
      and more persistent long-term fear memory. By contrast, these mice performed
      normally in hippocampus-dependent Morris maze. These experiments provide genetic
      evidence that GRP and its neural circuitry operate as a negative feedback
      regulating fear and establish a causal relationship between Grpr gene expression,
      LTP, and amygdala-dependent memory for fear.

PMID- 12526816
TI  - Poly-D,L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine
      delivery systems.
AB  - Adjuvants aimed at increasing the immunogenicity of recombinant antigens remain a
      focus in vaccine development. Worldwide, there is currently considerable care for
      the development of biodegradable microspheres as controlled release of vaccines,
      since the major disadvantage of several currently available vaccines is the need
      for repeated administration. Microspheres prepared from the biodegradable and
      biocompatible polymers, the polylactide (PLA) or polylactide-co-glycolide (PLGA),
      have been shown to be effective adjuvants for a number of antigens. This review
      mainly focuses on polylactide-co-poly(ethylene glycol) (PELA) microspheres
      adjuvant as vaccine delivery systems by summarizing our and other research
      groups' investigation on properties of the microspheres formulation encapsulating
      several kinds of antigens. The results indicate that compared with the commonly
      used PLA and PLGA, PELA showed several potentials in vaccine delivery systems,
      which may be due to the block copolymer have its capability to provide a
      biomaterial having a broad range of amphiphilic structure. PELA microspheres can
      control the rate of release of entrapped antigens and therefore, offer potential
      for the development of single-dose vaccines. The PELA microspheres have shown
      great potential as a next generation adjuvant to replace or complement existing
      aluminum salts for vaccine potential. The review mainly aims to promote the
      investigation of PELA microspheres adjuvant for antigens for worldwide
      researcher.

PMID- 12526817
TI  - Release characteristics of an azo dye from poly(ureaurethane) microcapsules.
AB  - The time course for the transfer of azo dyes from the microcapsule core of
      dioctylphthalate to the dispersing medium of methanol through a
      poly(ureaurethane) (PUU) membrane was measured for various average size
      microcapsules with a size distribution. The dye release curves are represented by
      a stretched exponential function C(t)=C(eq)[1-exp [-(t/tau(eff))(alpha)]], where
      C(t) is the concentration of the dye in methanol, C(eq) that at the equilibrium
      state, and t the time. The exponent alpha decreased by increasing the variance of
      the size distribution of microcapsules. The effective time constant tau(eff) was
      expressed by tau(eff)=c(0)<R(2)>/kappa(alpha), where <R(2)> and kappa(alpha) are
      the mean square of microcapsule radius and a correction for the size
      distribution, respectively. The characteristic proportional constant, c(0), was
      determined as 2.6+/-0.2 min/microm(2). From the value of the constant, the
      diffusion coefficient of the azo dye in the PUU membrane was evaluated as 2.6 x
      10(-12) cm(2)/s.

PMID- 12526818
TI  - Pancreatin enhanced erosion of and macromolecule release from 2,2-bis(2
      oxazoline)-linked poly(epsilon-caprolactone).
AB  - The degradation and erosion of solvent cast films and injection molded bars
      prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked
      poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid
      (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5,
      pancreatin present). After incubation of the polymer films (10 mg) and bars (70
      mg) in the medium, the resulting decrease in molecular weight (degradation) was
      determined by size exclusion chromatography and the weight loss of the
      preparations was measured. In addition, the effect of pancreatin on FITC-dextran
      (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double
      emulsion technique, was studied. No degradation or weight loss was observed for
      either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared
      to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars.
      In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars.
      Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF.
      Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O
      microparticles. In conclusion, the present results demonstrate the enzyme
      sensitivity of the novel PCL-O polymer. In addition, the results show that
      pancreatin present in intestinal fluid may substantially affect drug release from
      PCL based preparations.

PMID- 12526819
TI  - Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH
      sensitive biodegradable system for paclitaxel delivery.
AB  - The main objective of this study was to develop and characterize a pH-sensitive
      biodegradable polymeric nanoparticulate system for tumor-selective paclitaxel
      delivery. A representative hydrophobic poly(beta-amino ester) (poly-1) was
      synthesized by conjugate addition of 4,4'-trimethyldipiperidine with 1,4
      butanediol diacrylate. Poly-1 (M(n) 10,000 daltons) nanoparticles were prepared
      by the controlled solvent displacement method in an ethanol-water system in the
      presence of Pluronic) F-108, a poly(ethylene oxide) (PEO)-containing non-ionic
      surfactant. Control and PEO-modified nanoparticles were characterized by Coulter
      counter, scanning electron microscopy (SEM), zeta potential measurements, and
      electron spectroscopy for chemical analysis (ESCA). Polymer degradation studies
      were performed in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C.
      Paclitaxel loading capacities and efficiencies were determined and release
      studies were performed in Tween)-80 (0.1%, w/v)-containing PBS at 37 degrees C.
      Control and PEO-modified nanoparticles, labeled with rhodamine-123, were
      incubated with BT-20 cells to examine the uptake and cellular distribution as a
      function of time. PEO-modified nanoparticles with an average size of 100-150 nm
      and a positive surface charge of 37.0 mV were prepared. SEM analysis showed
      distinct smooth, spherical particles. The ether (-C-O-) peak of the C(1s)
      envelope in ESCA confirmed the surface presence of PEO chains. Polymer
      biodegradation studies showed that almost 85% of the starting material degraded
      after 6 days. The maximum paclitaxel loading efficiency attained was 97% at 1.0%
      (w/w) of the drug. Paclitaxel release studies showed that approximately 10% was
      released in the first 24 h, 80% after 3 days, and the entire content was released
      in approximately 5 days. After 1 h of incubation, a large fraction of the
      administered control and PEO-modified poly-1 nanoparticles was internalized in BT
      20 cells. Results of this study demonstrate that PEO-modified poly-1
      nanoparticles could provide increased therapeutic benefit by delivering the
      encapsulated drug to solid tumors.

PMID- 12526820
TI  - Mucoadhesive properties of carbopol or chitosan-coated liposomes and their
      effectiveness in the oral administration of calcitonin to rats.
AB  - Mucoadhesive liposomes were prepared by coating multilamellar liposomes with
      Carbopol (CP) in a similar manner to that used in the preparation of chitosan
      coated liposomes (CS-Lip) previously reported [Takeuchi et al., Chem. Pharm.
      Bull. 42 (1994) 1954-1956; Pharm. Res. 13 (1996) 896-901]. The positively charged
      liposomes containing dipalmitoylphosphatidylcholine (DPPC) and stearylamine at an
      optimum formulation ratio (40:1) could be coated with CP without aggregation of
      the liposomal particles during the coating process. The mucoadhesive properties
      of both the resultant polymer-coated liposomes (CP-Lip and CS-Lip) and the
      positively or negatively charged noncoated liposomes (Non-Lip) were evaluated
      using the rat intestine. The order was CS-Lip> or = CP-Lip>positively charged Non
      Lip>negatively charged Non-Lip. The adhesive property of CP-Lip decreased on
      increasing pH of the dispersing medium from pH 5.0 to 7.4, probably owing to the
      electric repulsion between CP-Lip and the mucus layer. The effectiveness of the
      liposomal formulations in oral administration of calcitonin was evaluated by
      measuring the change in the blood calcium concentration of rats. Administration
      of CP-Lip and CS-Lip containing calcitonin showed an enhanced and prolonged
      reduction in blood calcium concentration. The overall pharmacological effect of
      CP- and CS-Lips evaluated by means of the area under the plasma calcium
      concentration curve was 2.4 and 2.8 times higher than that of negatively and
      positively charged Non-Lips, respectively.

PMID- 12526821
TI  - Solid lipid microparticle formulations of the pyrethroid gamma-cyhalothrin
      incompatibility of the lipid and the pyrethroid and biological properties of the
      formulations.
AB  - Pyrethroids such as gamma-cyhalothrin (GCH) are valuable insecticides that
      possess a high and unwanted toxicity towards aquatic organisms. The aim of the
      present study was to test the ability of the solid lipid nanoparticle technology
      to reduce the aquatic toxicity and concurrently retain the insecticidal activity
      of GCH. Applying the lipid Compritol) 888 ATO and homogenising the crude o/w
      emulsions of melted GCH and compritol at different pressures, 150-1500 bar, solid
      lipid microparticle formulations were produced having average particle diameters
      between 0.3 and 100 microm. GCH had limited solubility in the solid lipid phase
      and probably the lipid showed transition from the alpha to the beta' crystal form
      upon storage. This resulted in expulsion of GCH from the lipid and appearance of
      GCH crystals in the water phase of the formulations. By using as surfactant
      polyvinyl alcohol instead of a mixture of Synperonic PE/F68 and sodium lauryl
      sulphate the appearance of GCH crystals was delayed. This delay was probably due
      to the fact that the GCH solubility was significantly lower in aqueous polyvinyl
      alcohol solutions than in solutions of the above-mentioned surfactant mixture.
      Compared with a traditional emulsifiable concentrate formulation of GCH the solid
      lipid microparticle formulations reduced the toxicity towards fish (Brachydanio
      rerio) and daphnia (Daphnia magna) by a factor 10 and 63, respectively. The solid
      lipid microparticle formulations and the emulsifiable concentrate formulation had
      about the same insecticidal activity on both Dysdercus cingulatus nymphs and
      Spodoptera littoralis larvae. Surprisingly the particle size of the solid lipid
      microparticle formulations only affected the biological activity slightly.

PMID- 12526822
TI  - Cationic cellulose hydrogels: kinetics of the cross-linking process and
      characterization as pH-/ion-sensitive drug delivery systems.
AB  - The cross-linking process of two cationic hydroxyethylcelluloses of different
      hydroxyethyl and ammonium group contents, polyquaternium-4 (PQ-4) and
      polyquaternium-10 (PQ-10), with ethylenglycol diglycidylether (EGDE) was
      characterized and optimized through rheometric analysis of the forming network.
      The influence of NaOH concentration, temperature, and EGDE concentration on the
      cross-linking rate were studied. The evolution of the elastic (G') and viscous
      (G") moduli, recorded in time-sweep experiments carried out at a fixed angular
      frequency, showed that the cross-linker requires a minimum of 0.05 M NaOH and 30
      degrees C to be active. The increase in G' and G" followed first order kinetics,
      the slopes of G' being higher than those corresponding to G". The gel time, i.e.
      the time at which the crossover of G' and G" occurs, decreases exponentially when
      temperature increases from 30 to 60 degrees C. Apparent activation energies,
      estimated from the gel times, ranged between 70 and 90 kJ/mol. The cross-linking
      rate was greater in PQ-4 than in PQ-10 owing to the initial lower viscosity and
      higher content in hydroxyethyl groups of the former. However, IR spectra of the
      final hydrogels suggest the formation of a similar number of cross-linking
      junctions in both polymer systems. The optimum conditions for hydrogel
      preparation were 60 degrees C in 0.10 M NaOH medium, and no depolymerization was
      observed. Such hydrogels were transparent, presented a smooth, continuous
      surface, and were superabsorbent in water. After drying in an oven, the degree of
      swelling was lower than that of freshly prepared hydrogels; the behavior of water
      uptake being Fickian. The hydrogels presented a significant loading capacity of
      diclofenac sodium, with which they interact through ionic and hydrophobic
      bonding. The affinity is kept at an acidic pH, preventing drug release. In
      contrast, at pH 8 the interactions are broken and the release process is
      sustained for more than 4 h. The results also indicate that the ionic strength as
      well as the initial pH of the medium, when the release was evaluated switching
      the pH from acidic to basic, are two critical factors which have to be considered
      to extract conclusions about the behavior of the hydrogels as site-specific
      delivery systems under in vivo conditions.

PMID- 12526823
TI  - Feeding liquid, non-ionic surfactant and cyclodextrin affect the properties of
      insulin-loaded poly(lactide-co-glycolide) microspheres prepared by spray-drying.
AB  - The potential of spray-drying technique for the encapsulation in poly(lactide-co
      glycolide) (PLGA) microspheres of bovine insulin, a poorly stable peptide, has
      been investigated. Insulin-loaded microspheres were prepared by spray-drying
      different feeding liquids containing insulin and PLGA, that is a S/O dispersion,
      a W/O emulsion or an acetic acid solution. In the case of the emulsion, insulin
      was also co-encapsulated with either non-ionic surfactants such as polysorbate 20
      and poloxamer 188, or complexing agents such as HPbetaCD. In the microspheres
      prepared from the acetic acid solution of insulin and PLGA, HPbetaCD was tested.
      Microspheres containing surfactants were aggregated, whereas good quality
      particles displaying a mean diameter in the range 12.1-27.9 microm were produced
      in the other cases. Insulin was efficiently loaded inside microspheres except for
      S/O formulation (only 22% of total insulin content was entrapped). The impact of
      the microencapsulation process on insulin chemical and conformational stability
      was assessed by HPLC, circular dichroism and turbidimetry studies. Under the
      adopted manufacture conditions, insulin was encapsulated in the native state and
      its chemical and conformational stability was preserved along the fabrication
      process. The formulations containing only insulin displayed low burst effects (6
      11%), whereas the addition of surfactants resulted in much higher burst effects
      (49-54%) and faster release rate. The co-encapsulation of HPbetaCD slowed down
      the overall release rate and, in the case of microspheres prepared from the
      emulsion, allowed a constant insulin release up to 45 days. The study of insulin
      stability along the release phase showed that insulin was released in the intact
      form and un-released insulin was stable inside all the microsphere formulations.
      We conclude that insulin can be effectively encapsulated in PLGA microspheres by
      the spray-drying technique. Additives with complexing properties such as HPbetaCD
      have demonstrated a potential in optimizing the release rate of insulin when used
      in microspheres prepared from W/O emulsions.

PMID- 12526824
TI  - Prodrugs of purine and pyrimidine analogues for the intestinal di/tri-peptide
      transporter PepT1: affinity for hPepT1 in Caco-2 cells, drug release in aqueous
      media and in vitro metabolism.
AB  - A general drug delivery approach for increasing oral bioavailability of purine
      and pyrimidine analogues such as acyclovir may be to link these compounds
      reversibly to stabilized dipeptide pro-moieties with affinity for the human
      intestinal di/tri-peptide transporter, hPepT1. In the present study, novel L-Glu
      Sar and D-Glu-Ala ester prodrugs of acyclovir and 1-(2-hydroxyethyl)-linked
      thymine were synthesized and their affinities for hPepT1 in Caco-2 cells were
      determined. Furthermore, the degradation of the prodrugs was investigated in
      various aqueous and biological media and compared to the corresponding hydrolysis
      of the prodrug valaciclovir. Affinity studies showed that the L-Glu-Sar prodrugs
      had high affinity for hPepT1 (K(i) approximately 0.2-0.3 mM), whereas the D-Glu
      Ala prodrugs had poor affinity (K(i) approximately 50 mM). The pH-rate profiles
      of the prodrugs D-Glu[1-(2-hydroxyethyl)thymine]-Ala and L-Glu[acyclovir]-Sar
      showed specific base catalyzed degradation at pH above 4.5 and 5.5, respectively.
      This implicates that the degradation rates at pH approximately 7.4 (t(1/2)
      approximately 3.5 and 5.5 h) are approximately 25 times faster than at upper
      small intestinal pH approximately 6.0. In 10% porcine intestinal homogenate and
      80% human plasma the half-lives of the L-Glu-Sar prodrugs were approximately
      between 45 and 90 min indicating a limited enzyme catalyzed degradation. In
      contrast, valaciclovir underwent extensive enzyme catalyzed hydrolysis in 10%
      porcine intestinal homogenate (t(1/2) approximately 1 min). In conclusion, L-Glu
      Sar may potentially function as pro-moiety for purine and pyrimidine analogues,
      where release of parent compound primarily is controlled by a specific base
      catalyzed hydrolysis. Acyclovir is quantitatively released at the relevant pH
      7.4, whereas the 1-(2-hydroxyethyl)-linked thymine is released instead of the
      parent compound thymine.

PMID- 12526825
TI  - A computational model for particle size influence on drug absorption during
      controlled-release colonic delivery.
AB  - The effect of particle size on the percent drug absorbed is computationally
      modeled for controlled-release dosage forms that deliver drug particles to the
      colon. The relative benefit of reducing particle size is mapped on a diagram of
      the drug's absorption rate constant (estimated from rat intestinal perfusion,
      CACO-2 or human intubation permeation rates) versus the drug's solubility. Some
      drugs fall into a limit of high percentage absorption even with large particles
      such that particle size reduction has little impact. Another group of drugs is
      solubility limited such that even with small particles, absorption is negligible.
      Between the two regions, only drugs with sufficiently high absorption rates are
      influenced by the drug dissolution rate and thereby the particle size. The size
      of this region is a function of dosing rate. Comparisons between calculated
      particle size effects on colon absorption as a function of colon volume suggest
      caution when using animal models to predict bioavailability from colonic drug
      delivery. This volume dependence also suggests that the particle size influence
      will vary as a function of the digestive cycle.

PMID- 12526826
TI  - Analysis and prediction of absorption behavior of colon-targeted prodrug in rats
      by GI-transit-absorption model.
AB  - The gastrointestinal-transit-absorption (GITA) model is useful for the analysis
      and the prediction of the absorption behavior of drugs orally administered as
      solutions. In the present study, we tried to predict the plasma concentration
      time profile of a colon-targeted prodrug, salicylazosulfanilic acid (SASA), and
      its parent drug, 5-aminosalicylic acid (5-ASA) which is regenerated after dosing.
      Prediction of plasma concentration-time profiles for SASA and 5-ASA was performed
      based on the GITA model using parameters describing GI-transit kinetics, the
      absorption in each GI segment, and the regeneration of 5-ASA in cecum. Plasma
      concentration-time profiles of both SASA and 5-ASA after oral administration of
      SASA were predicted very well by introducing a factor for the first-pass
      elimination of 5-ASA into the GITA model. The simulation study using the
      parameters obtained in the present study showed that about 94.7% of SASA reaches
      the cecum, where 5-ASA is regenerated very rapidly and 76.0% of 5-ASA is
      absorbed. Furthermore, the bioavailability of 5-ASA was estimated to be 0.330
      because of the first-pass elimination through both cecum and liver. In
      conclusion, the absorption behaviors of a prodrug and its regenerated parent drug
      can be predicted very well and be clarified successfully using the GITA model.

PMID- 12526827
TI  - Influence of ion pairing on topical delivery of retinoic acid from
      microemulsions.
AB  - The purpose of the present study was to determinate the significance of ion
      pairing on the topical permeation of retinoic acid (R.A) using microemulsions as
      delivery vehicles. Phenylalanine methyl ester, phenylalanine ethylester,
      histidine methyl ester, tryptophan methyl ester and valine methyl ester were used
      as counter ions. Results of diffusion studies through polydimethylsiloxane
      membrane (PDMS) indicate that retinoic acid permeation from ethanol-pH 6.4 buffer
      mixture significantly increased in the presence of counter ions. A linear
      relationship was found between apparent partition coefficients and permeation
      coefficients. The highest values were with valine methyl ester and phenylalanine
      ethyl ester. In order to develop alternative formulations for topical
      administration of R.A, microemulsions were evaluated as delivery vehicles. Oil-in
      water (O/W) and water-in-oil (W/O) microemulsion formulations were prepared using
      water, isopropyl myristate, lecithin, caprylyl-capryl glucoside and ethanol or
      1,2 hexanediol. Experiments with PDMS membranes showed decreasing permeabilities
      of R.A from microemulsions in the presence of counter ions. This was related to
      the increased lipophilicity and different vehicle membrane affinity of the ion
      pairs The ability of the systems to deliver R.A through the skin was evaluated in
      vitro using pig-skin. R.A permeabilities were much lower with microemulsions than
      with solution, while a large increase in R.A skin deposition was observed only
      from O/W microemulsions in the presence of counter ions. The depth of skin
      accumulation was below 100 microm after 24 h application. The results suggest
      that O/W microemulsions containing a counter ion can be used to optimise drug
      targeting without a concomitant increase in systemic absorption.

PMID- 12526828
TI  - Lipid-derivatized poly(ethylene glycol) micellar formulations of benzoporphyrin
      derivatives.
AB  - In this paper, we describe the development of micellar formulations for
      increasing the solubility of lipophilic benzoporphyrins. Using a simple procedure
      that is readily adaptable for large-scale manufacturing, both A-ring (1) and B
      ring isomers (2) of benzoporphyrins could be readily formulated, at
      concentrations up to 1-2 mg/ml, into small micelles (<20 nm in diameter) of
      methoxypoly(ethylene glycol) (M(r) 2000) covalently attached to the lipid anchor
      distearoylphosphatidylethanolamine (mPEG-DSPE). The formulations spontaneously
      formed upon hydration of a thin film containing mPEG-lipid and photosensitizer
      and were stable upon storage at 4 degrees C for at least 1 month. Self
      association of the B-ring benzoporphyrin isomer in micelles could be efficiently
      inhibited by either increasing the molar ratio of mPEG(2000)-DSPE to
      benzoporphyrin or by increasing the pH of the preparation to pH 8.5. The
      formulation could be freeze-dried and stored indefinitely in the lyophilized
      form, with restoration of the original properties upon reconstitution. In vivo,
      the A-ring benzoporphyrin, verteporfin, had higher levels of delivery and greater
      tumor control in mice than the B-ring derivative when formulated in mPEG(2000)
      DSPE micelles and administered intravenously. mPEG(2000)-DSPE micellar
      formulations also showed tumor control when administered by a single intratumoral
      injection followed by light irradiation to the tumor within 45-60 min after drug
      administration. PEG-containing micellar formulations may be a promising delivery
      system for benzoporphyrin monoesters for clinical applications.

PMID- 12526829
TI  - Gene expression and mucosal immune responses after vaginal DNA immunization in
      mice using a controlled delivery matrix.
AB  - IgA antibodies in the vaginal tract are essential as a first defense line against
      microorganisms that enter the body via mucosal surfaces. Several studies have
      shown that direct application of DNA to the vaginal mucosal surface can induce
      secretion of IgA molecules specific to the expressed protein. The major challenge
      of formulating effective vaccines is to overcome the barriers to DNA
      administration caused by the estrus cycle and physical environment of the vaginal
      tract. In this study, we investigated whether controlled delivery of DNA to the
      vaginal surface would induce long-term IgA antibody production by applying
      controlled delivery matrices to the vaginal tract. The controlled DNA delivery
      matrices were composed of poly(ethylene-co-vinyl acetate) (EVAc) and loaded with
      a model plasmid encoding sperm-specific lactate dehydrogenase C(4) (LDH-C(4)).
      These EVAc matrices provided a controlled and sustained DNA release to the
      vaginal mucosal surface. The DNA released from the EVAc disks was functionally
      active and capable of transfecting vaginal tissues. When inserted into the
      vaginal tract of mice, the DNA-loaded EVAc matrices triggered the immune system
      and induced specific IgA to LDH-C(4) in the vaginal secretions. These results
      demonstrate that the EVAc disks are efficient and convenient vehicles for
      delivering DNA to the vaginal tract and providing long-term local immunity.

PMID- 12526830
TI  - Galactosylated chitosan (GC)-graft-poly(vinyl pyrrolidone) (PVP) as hepatocyte
      targeting DNA carrier. Preparation and physicochemical characterization of GC
      graft-PVP/DNA complex (1).
AB  - Galactosylated chitosan was conjugated with poly(vinyl pyrrolidone) (PVP) as a
      hydrophilic group. The complex formation of GC-graft-PVP (GCPVP)/DNA complexes
      was confirmed by agarose gel electrophoresis. The morphology of the complex
      observed by atomic force microscopy had a compact and spherical shape, around 40
      nm particle sizes at a charge ratio of 3. The binding strength of GCPVP 10K/DNA
      complex measured by ethidium bromide binding assay was superior to that of the
      GCPVP 50K/DNA one, probably attributable to its higher flexibility due to the
      smaller size, whereas the DNase I protection of GCPVP 10K/DNA complex was
      inferior to that of the GCPVP 50K/DNA one. This indicated that effective complex
      formation required both higher binding strength and minimal molecular weight of
      polycation enough to induce the condensation of DNA. The DNA-binding property of
      GCPVP mainly depended on the molecular weight of chitosan and composition of PVP.

PMID- 12526831
TI  - Gene packaging with lipids, peptides and viruses inhibits transfection by
      electroporation in vitro.
AB  - To develop improved methods of gene delivery, packaging DNA in chemical or viral
      vectors could increase electroporation-mediated transfection. To test this
      hypothesis, electroporation was applied to DU145 prostate cancer cells incubated
      with green fluorescent protein-encoded DNA plasmid either naked or packaged with
      cationic lipid (Lipofectin), polycationic peptide (salmon protamine) or
      retroviral vectors (Moloney murine leukemia viruses) and then assayed for gene
      expression and cell viability. Cationic lipid or electroporation alone each
      significantly increased transfection, but their combination was less effective.
      Addition of protamine peptide during electroporation was also less effective than
      electroporation alone. The combination of retroviral vectors and electroporation
      transfected fewer cells than retrovirus alone. We conclude that the combination
      of electroporation with chemical or viral vectors does not improve gene
      transfection in vitro.

PMID- 12526835
TI  - Synthesis of monomethylated dioscin derivatives and their antitumor activities.
AB  - All possible eight monomethylated dioscin derivatives (1-8) were synthesized.
      Their inhibitory activities against P388 and A-549 cells were determined, and the
      results indicate that six of the eight hydroxyls of dioscin are the 'key polar
      groupings' for tumor inhibitory activities.

PMID- 12526836
TI  - Conformational evaluation of some 4-deoxyhex-4-enopyranose derivatives and their
      use in the preparation of a previously undescribed class of 3-thio-L
      sorbopyranosides and their 6-C-methoxy analogues.
AB  - A new series of thio-substituted sugars were synthesised relying on the totally
      regio- and stereoselective cycloaddition of 4-deoxyhex-4-enopyranose derivatives
      to 'in situ' generated oxothiones. Conformational studies of the above
      unsaturated sugars showed a marked prevalence of the all-axial conformer.

PMID- 12526837
TI  - Synthesis and induction of apoptosis in B cell chronic leukemia by diosgenyl 2
      amino-2-deoxy-beta-D-glucopyranoside hydrochloride and its derivatives.
AB  - 2-Acetamido-2-deoxy-D-glucose hydrochloride (D-glucosamine hydrochloride) has
      been used for the preparation of 1,3,4,6-tetra-O-acetyl-2-deoxy-2
      trifluoroacetamido-beta- (4) and 2-tetrachlorophthalimido-alpha,beta-D
      glucopyranose (6), which have been transformed into the appropriate bromides and
      the chloride. Both bromo and chloro sugars were used as a glycosyl donors for the
      glycosylation of diosgenin [(25R)-spirost-5-en-3beta-ol]. These condensations
      were conducted under mild conditions, using silver triflate as a promoter, and
      gave diosgenyl glycosides 9 and 12. Each of them was converted into diosgenyl 2
      amino-2-deoxy-beta-D-glucopyranoside hydrochloride (11) and N-acylamido
      derivatives. The structures of all new glycosides were established by 1H and 13C
      NMR spectroscopy. These diosgenyl glycosides are the first saponins containing
      the D-glucosamine residue that have been synthesized. These compounds show
      promising antitumor activities. The synthetic saponins increase the number of
      apoptotic B cells, in combination with cladribine (2-CdA), that are isolated from
      chronic lymphotic leukemia (B-CLL) patients.

PMID- 12526838
TI  - Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose, and
      their analogs.
AB  - Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex
      3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L
      sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of
      diastereomeric ketoses underwent acetylation and pyranose ring opening under the
      action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine
      (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1
      (indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1
      (indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically.
      Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in
      admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose
      (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a).
      Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3
      yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed
      for N-methyl- and N-methoxyindole derivatives.

PMID- 12526839
TI  - Fucoidans from the brown seaweed Adenocystis utricularis: extraction methods,
      antiviral activity and structural studies.
AB  - The brown seaweed Adenocystis utricularis (family Adenocystaceae, order
      Ectocarpales sensu lato) was extracted in parallel with three solvents usually
      utilized for obtaining fucoidans: distilled water, 2% calcium chloride solution
      and diluted hydrochloric acid (pH 2) solution. In each case, the extraction was
      effected at room temperature and then at 70 degrees C. The extraction yields and
      characteristics of the products were similar in the three cases, with only minor
      differences. The analytical features of the products indicate that two different
      types of fucoidans are present in this seaweed. One of them, mostly extracted at
      room temperature, is composed mainly of L-fucose, D-galactose and ester sulfate
      (the 'galactofucan'). The other product (the 'uronofucoidan') is the major
      component of the extracts obtained at 70 degrees C. It is composed mainly of
      fucose, accompanied by other monosaccharides (mostly Man, but also Glc, Xyl, Rha
      and Gal), significant amounts of uronic acids and low proportions of sulfate
      ester. Fractionation with the cationic detergent cetrimide has allowed achieving
      a better separation of the galactofucan and uronofucoidan components. The
      galactofucans show a high inhibitory activity against herpes simplex virus 1 and
      2, with no cytotoxicity, whereas the uronofucoidans carry no antiviral activity.
      Structural studies on the galactofucan fractions were carried out by methylation
      analysis, desulfation and NMR spectroscopy. The fucan constituent is mainly
      composed of 3-linked alpha-L-fucopyranosyl backbone, mostly sulfated at C-4, and
      branched at C-2 with non-sulfated fucofuranosyl and fucopyranosyl units, and 2
      sulfated fucopyranosyl units. The galactan moiety is more heterogeneous, with
      predominant D-galactopyranose units linked on C-3 and C-6, and sulfation mostly
      on C-4, even in terminal non-reducing units. It may be inferred that at least
      some of these galactose units carry the alpha-configuration.

PMID- 12526840
TI  - Conjugation of meningococcal lipooligosaccharides through their lipid A terminus
      conserves their inner epitopes and results in conjugate vaccines having improved
      immunological properties.
AB  - The importance of conserved inner saccharide epitopes to the immune performance
      of meningococcal lipooligosaccharide-protein conjugate vaccines was demonstrated
      in the following experiments. Two different oligosaccharides were obtained by
      chemical degradations of the same L7 lipooligosaccharide, and both were linked
      terminally to tetanus toxoid. One was a truncated oligosaccharide in which the
      inner epitopes were incomplete and was obtained by mild acid hydrolysis of the L7
      lipooligosaccharide. This oligosaccharide was conjugated by direct reductive
      amination through its newly exposed terminal Kdo residue. The second, a full
      length oligosaccharide, was obtained by O-deacylation of the L7
      lipooligosaccharide, with subsequent removal of phosphate substituents from its
      lipid A moiety using alkaline phosphatase. This permitted the full-length
      oligosaccharide to be conjugated directly to tetanus toxoid by reductive
      amination through its newly exposed terminal 2-N-acyl-2-deoxy-D-glucopyranose
      residue. Comparison of the immune performance of the two conjugates in mice
      revealed, that while both were able to induce significant levels of L7
      lipooligosaccharide-specific IgG antibody, the conjugate made with the full
      length saccharide was able to induce antibodies with increased bactericidal
      activity against homologous meningococci.

PMID- 12526841
TI  - Peracetylated 1,6-dibromo-D-glucitol as efficient precursor of 1,6-diiodo and
      some mono-, disubstituted and heterocyclic D-glucitol derivatives.
AB  - 2,3,4,5-Tetra-O-acetyl-1,6-dibromo-1,6-dideoxy-D-glucitol (1a) obtained from D
      glucitol was easily transformed into the 1,6-diiodo derivative in excellent yield
      (97%) by reaction with an excess of sodium iodide in refluxing butanone in 2 h.
      When the reaction time was prolonged to 24 h and the crude product was
      acetylated, 1,2,3,4,5-penta-O-acetyl-6-deoxy-6-iodo-D-glucitol and D-glucitol
      hexaacetate were isolated in 50 and 26% yields, respectively. The
      monodehalogenation then took place regioselectively at C-1. This regioselectivity
      allowed the synthesis of some mono- and disubstituted derivatives of D-glucitol.
      Thus, the peracetylated derivatives of D-glucitol, 6-bromo, 6-bromo-1-S-butyl, 6
      bromo-1-S-octyl, 6-S-butyl, 6-S-butyl-1-S-octyl, 1-S-butyl, 1,6-di-S-octyl and 6
      S-phenyl were synthesised in good to excellent yields. With S= as binucleophilic
      reagent, 1a gave mainly the thiepane derivative (75%) plus the 1-S-acetyl-2,6
      anhydro-D-glucitol derivative as a by-product (10%).

PMID- 12526842
TI  - Synthesis and solid state 13C and 1H NMR analysis of new oxamide derivatives of
      methyl 2-amino-2-deoxy-alpha-D-glucopyranoside and ester of amino acids or
      dipeptides.
AB  - The syntheses of new oxamide derivatives of methyl 2-amino-2-deoxy-alpha-D
      glucopyranoside and amino acid or peptide esters are presented. The reaction of
      methyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside and oxalyl
      chloride gave N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-alpha-D-glucopyranosid-2-yl)
      oxamic acid chloride which on reaction with the ester of Gly, L-Ala, L-Phe,
      GlyGly, Gly-L-Phe and Gly-L-Ala afforded N-(methyl 3,4,6-tri-O-acetyl-2-deoxy
      alpha-D-glucopyranosid-2-yl), N'-oxalyl-amino acid or dipeptide esters. The
      structure of the oxamides was studied using 1H, 13C NMR in solution and solid
      state.

PMID- 12526843
TI  - Chemical synthesis of methyl 6'-alpha-maltosyl-alpha-maltotrioside and its use
      for investigation of the action of starch synthase II.
AB  - The branched pentasaccharide methyl 6'-alpha-maltosyl-alpha-maltotrioside was
      chemically synthesised and investigated as a primer for particulate starch
      synthase II (SSII) using starch granules prepared from the low-amylose pea mutant
      lam as the enzyme source. For chemical synthesis, the trichloroacetimidate
      activation method was used to synthesise methyl O-(2,3,4,6-tetra-O-benzyl-alpha-D
      glucopyranosyl)-(1-->4)-O-(2,3,6-tri-O-benzyl-alpha-D-glucopyranosyl)-(1-->6)-O
      [(2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl-(1-->4)]-O-(2,3-di-O-benzyl-alpha
      D-glucopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-alpha-D-glucopyranoside, which was
      then debenzylated to provide the desired branched pentasaccharide methyl 6'-alpha
      maltosyl-alpha-maltotrioside as documented by 1H and 13C NMR spectroscopy. Using
      a large excess of the maltoside, the pentasaccharide was tested as a substrate
      for starch synthase II (SSII). Both of the non-reducing ends of methyl 6'-alpha
      maltosyl-alpha-maltotrioside were extended equally resulting in two
      hexasaccharide products in nearly equal amounts. Thus, SSII catalyses an
      equimolar and non-processive elongation reaction of this substrate. Accordingly,
      the presence of the alpha-1,6 linkages does not dictate a specific structure of
      the pentasaccharide in which only one of the two non-reducing ends are available
      for extension.

PMID- 12526844
TI  - A facile protocol for direct conversion of unprotected sugars into phenyl 4,6-O
      benzylidene-per-O-acetylated-1,2-trans-thioglycosides.
AB  - A short and practical methodology for conversion of unprotected D-glucose,
      maltose, cellobiose and lactose into the corresponding phenyl 4,6-O-benzylidine
      per-O-acetylated-1,2-trans-thioglycosides is described. The protocol is based on
      the execution of five reaction steps (bromoacetylation, thiophenolysis under
      phase transfer catalysis conditions, deacetylation, benzylidenation and
      acetylation) in one continuous procedure and provides a fast access to the title
      compounds as pure crystalline products without chromatographic purification.

PMID- 12526846
TI  - Genomic variability among enteric pathogens: the case of the mutS-rpoS intergenic
      region.
AB  - The mutS-rpoS intergenic region of enteric bacteria ranges in size from 88 bp in
      Yersinia to > 12000 bp in Salmonella. We interpret this expansion as the result
      of the horizontal transfer of segments of DNA from diverse origins. Both
      comparative genomic analysis and selective sequencing of a variety of Escherichia
      coli pathogens have provided additional evidence for reassortment of segments
      within this region.

PMID- 12526847
TI  - In search of the minimal Escherichia coli genome.
AB  - Recent plans announced for the systematic cataloging of the minimal Escherichia
      coli gene set, the phenotypes of all mutations, the expression levels of every
      transcript and gene product, and the interactions of all genetic loci or their
      gene products point the way towards a new frontier in the biology of model
      organisms. Powerful tools for this endeavor are emerging, and efforts to organize
      the E. coli community are under way. The anticipated benefit is a functional
      model of the bacterial cell.

PMID- 12526848
TI  - NADPH oxidase: an enzyme for multicellularity?
AB  - Multicellularity has evolved several times during the evolution of eukaryotes.
      One evolutionary pressure that permits multicellularity relates to the division
      of work, where one group of cells functions as nutrient providers and the other
      in specialized roles such as defence or reproduction. This requires signalling
      systems to ensure harmonious development of multicellular structures. Here, we
      show that NADPH oxidases are specifically present in organisms that differentiate
      multicellular structures during their life cycle and are absent from unicellular
      life forms. The biochemical properties of these enzymes make them ideal
      candidates for a role in intercellular signalling.

PMID- 12526849
TI  - The magnificent seven.

PMID- 12526850
TI  - Challenging the trade-off model for the evolution of virulence: is virulence
      management feasible?
AB  - Progress in understanding the evolution of infectious diseases has inspired
      proposals to manage the evolution of pathogen (including parasite) virulence. A
      common view is that social interventions that lower pathogen transmission will
      indirectly select lower virulence because of a trade-off between transmission and
      virulence. Here, we argue that there is little theoretical justification and no
      empirical evidence for this plan. Although a trade-off model might apply to some
      pathogens, the mechanism appears too weak for rapid selection of substantial
      changes in virulence. Direct selection against virulence itself might be a more
      rewarding approach to managing the evolution of virulence.

PMID- 12526851
TI  - The structure and function of drug pumps: an update.
AB  - Our understanding of the exact mechanisms used by the transmembrane protein pumps
      that confer cellular resistance to cytotoxic drugs has improved enormously with
      the recent determination of the structures of three Escherichia coli
      transporters, two belonging to the ATP-binding cassette (ABC) superfamily and one
      to the resistance-nodulation-cell division (RND) family. Although these studies
      do not provide an insight into how drug pumps can recognize several structurally
      unrelated drugs, important advances have been also made in this area. Information
      on the molecular basis of multidrug recognition has been provided by determining
      the structure of transcriptional regulators that can bind, often structurally
      unrelated, cytotoxic drugs and control the expression of drug pumps.

PMID- 12526852
TI  - Candida biofilms and their role in infection.
AB  - Pathogenic fungi in the genus Candida can cause both superficial and serious
      systemic disease, and are now recognized as major agents of hospital-acquired
      infection. Many Candida infections involve the formation of biofilms on implanted
      devices such as indwelling catheters or prosthetic heart valves. Biofilms of
      Candida albicans formed in vitro on catheter material consist of matrix-enclosed
      microcolonies of yeasts and hyphae, arranged in a bilayer structure. The biofilms
      are resistant to a range of antifungal agents currently in clinical use,
      including amphotericin B and fluconazole, and there appear to be multiple
      resistance mechanisms. Recent studies with mixed biofilms containing Candida and
      bacterial species suggest that extensive and striking interactions occur between
      the prokaryotic and eukaryotic cells in these adherent populations.

PMID- 12526853
TI  - Silence of the strands: RNA interference in eukaryotic pathogens.
AB  - Double-stranded (ds) RNA interference (RNAi) is a recent technological advance
      that enables researchers to reduce gene expression at the post-transcriptional
      level. This form of RNA silencing is initiated by dsRNA, expressed in or
      introduced into a cell of interest, which triggers homology-dependent degradation
      of the corresponding mRNA. This versatile technique has remarkable promise as a
      tool for the study of eukaryotic pathogens. Protozoan parasites and pathogenic
      fungi often resist manipulation using standard molecular genetic approaches.
      Researchers studying these organisms need flexible molecular tools, particularly
      to exploit newly sequenced genomes; this review offers a practical guide to
      establishing RNAi in pathogenic eukaryotes.

PMID- 12526854
TI  - The cellular paradigm of chlamydial pathogenesis.
AB  - Diseases caused by Chlamydia are based on intense and chronic inflammation
      elicited and maintained by reinfection or persistent infection. The traditional
      view in the field is that disease is mediated by antigen-dependent delayed-type
      hypersensitivity or autoimmunity. This immunological paradigm has served as the
      basis for years of chlamydial research but the mechanism or the antigen that
      causes pathology has yet to be unequivocally revealed. Recent research on
      responses elicited in Chlamydia-infected cells defines a new direction for our
      understanding of this microorganism-host interaction and provides the basis for a
      reassessment of disease mechanisms. Chlamydia-infected non-immune mammalian cells
      produce proinflammatory chemokines, cytokines, growth factors and other cellular
      modulators. This cellular response to infection supports an alternative
      hypothesis for chlamydial pathogenesis: the inflammatory processes of chlamydial
      pathogenesis are elicited by infected host cells and are necessary and sufficient
      to account for chronic and intense inflammation and the promotion of cellular
      proliferation, tissue remodeling and scarring, the ultimate cause of disease
      sequelae.

PMID- 12526855
TI  - Azathioprine and anti-TNF alpha therapies in Crohn's disease: a review of
      pharmacology, clinical efficacy and safety.
AB  - Crohn's disease (CD), a chronic relapsing inflammatory condition of the
      intestines, is a common cause of gastrointestinal morbidity in young people.
      Although the aetiology of CD is unknown, host, genetic and environmental
      influences are clearly important. Glucocorticoids remain the mainstay of
      treatment for active CD, however only two-third of patients will respond and side
      effects are considerable. Surgery is often undesirable or impracticable and
      therefore alternative medical strategies have been sought. In recent years, there
      has been much interest in two areas of IBD therapy-the use of established
      immunomodulators, and the development of novel biological therapies. In this
      review, we have selected two areas of particular controversy-the use of purine
      analogues (azathioprine (AZA) and 6-mercaptopurine (6-MP)) and the introduction
      of anti-tumour necrosis factor alpha (TNFalpha) therapy and have examined the
      data for efficacy, safety and tolerability of these medications.

PMID- 12526856
TI  - Effects of methyl methacrylate on Ca2+ uptake of cardiac sarcoplasmic reticulum.
AB  - In isolated cardiac sarcoplasmic reticulum (SR) vesicles, methyl methacrylate
      (2.5-100mM) directly inhibited initial rates of Ca2+ uptake as well as the
      maximal uptake. Inhibition of SR Ca2+ uptake by methyl methacrylate was
      concentration-dependent, and the highest concentration of methyl methacrylate
      (100mM) almost completely inhibited the SR Ca2+ uptake. EC(50) of methyl
      methacrylate in percent inhibition of SR Ca2+ uptake was 16.1, 31.9, and 53.4mM
      at pCa 7.0, 6.6, and 6.0, respectively. At low Ca2+ concentrations (0.1-1
      microM), SR vesicles treated with 20mM methyl methacrylate showed the decreased
      Ca2+ uptake rates. However, further increase of Ca2+ concentration to pCa 5.5
      abolished the inhibitory effect of methyl methacrylate on SR Ca2+ uptake, showing
      no difference between the control and the methyl methacrylate-treated SR
      vesicles. From these results we could conclude that methyl methacrylate exerts a
      direct inhibition of cardiac SR Ca2+ uptake. This mechanism, at least in part,
      might contribute to the profound hypotension induced by methyl methacrylate.
      Supplementation of calcium ion appears to reduce the methyl methacrylate-induced
      cardiovascular disturbances efficiently.

PMID- 12526857
TI  - Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed
      cholesterol-rich diets.
AB  - To study the influence of polymerised polyphenolics (PP), a fraction of silymarin
      (SM), on lipids and oxidant status, rats were fed high-cholesterol (1%), high-fat
      (10%) diets containing either lard fat (LFD) rich in saturated/monounsaturated
      fatty acids, or currant oil (COD) rich in polyunsaturated fatty acids. PP and SM
      were administered as dietary supplements (0.1-0.5-1.0%) for 3 weeks. PP (1%)
      decreased cholesterol (C) in VLDL (from 0.72+/-0.08 mmol l(-1) in LFD control to
      0.35+/-0.07 mmol l(-1), P<0.01, and from 0.33+/-0.05 mmol l(-1) in COD control to
      0.09+/-0.02 mmol l(-1), P<0.001), and increased HDL-C/VLDL-C ratio, however,
      without effect on the total plasma C and LDL-C. Liver C content (LFD 19.32+/-1.50
      micromol g(-1), COD 18.64+/-2.13 micromol g(-1), N.S.) decreased after PP (1%) to
      12.24+/-0.76 micromol g(-1), P<0.01, and 8.78+/-0.95 micromol g(-1), P<0.001,
      respectively. Triacylglycerols (TAG) in plasma and VLDL decreased after PP in the
      LFD group only, which displayed higher TAG levels than the COD group. Likewise,
      LFD caused a higher liver TAG content than did COD (31.16+/-3.00 micromol g(-1)
      versus 17.31+/-1.48 micromol g(-1), P<0.01), and PP (1%) decreased liver TAG only
      in rats fed LFD (19.55+/-2.43 micromol g(-1), P<0.02). Blood glutathione (GSH)
      increased after PP (1%) in the LFD group from 0.97+/-0.11 to 1.54+/-0.19 mmol l(
      1) (P<0.05) and in the COD group from 0.58+/-0.15 to 1.23+/-0.10 mmol l(-1)
      (P<0.01), while liver GSH and plasma TBARS did not change. On principle, effects
      of PP were dose-dependent and parallel to SM. These results suggest that the
      polyphenolic fraction of SM positively modifies lipoprotein profile, counteracts
      the development of fatty liver and ameliorates an antioxidant status in
      circulation.

PMID- 12526858
TI  - Cyclosporin effect on noradrenaline release from the sympathetic nervous endings
      of rat aorta.
AB  - Arterial hypertension is one of the main side effects of cyclosporin treatment
      and seems to be due to activation of the sympathetic nervous system. Some authors
      hypothesized that cyclosporin may act on the sympathetic nervous endings
      increasing catecholamine release, in agreement with our previous works which
      demonstrated an increase in rat plasma catecholamine levels after 30 mg/kg per
      day cyclosporin treatment for 7 weeks. Therefore, the aim of this work was to
      study the cyclosporin mechanism responsible for that increase in plasma
      catecholamines. Male Wistar rats were used. Noradrenaline release was performed
      in vitro experiments after loading rat aorta abdominal segments with 3H
      noradrenaline (3H-NA). The release of 3H-NA was measured after electrical
      stimulation in the presence of 10(-6)M cyclosporin. In another set of experiments
      electrical stimulation was replaced by a pulse addition of cyclosporin (10(-6)M).
      Another group of rats was treated with 30 mg/kg per day cyclosporin for 7 weeks
      and catecholamine contents in aorta abdominal segments and adrenals were measured
      by high performance liquid chromatography system with electrochemical detection
      (HPLC-ECD). An increase in the 3H-NA release was observed in both types of in
      vitro experiments. Since cocaine abolished these cyclosporin effects, the
      obtained results suggest that cyclosporin may act on the catecholamine
      transporter across the membrane. In addition, after the 7 weeks of cyclosporin
      treatment, a significant decrease in catecholamine aorta contents was verified
      but in adrenals there was no difference regarding to controls. However, the
      dopamine synthesis/degradation ratio measured by the DA/DOPAC ratio suggests an
      increase in dopamine synthesis. These facts are in agreement with the enhanced
      plasma catecholamine levels and with the hypothesis of tissue catecholamine
      depletion. However, they do not explain the increase in plasma adrenaline levels,
      since adrenaline is a reflex of adrenal activity. The synthesized dopamine in
      adrenals seems to be unable to reach vesicles and to be metabolized in
      adrenaline. The observed decrease in HVA adrenal levels may be a consequence of
      extraneuronal uptake inhibition or inhibition by cyclosporin of the direct o
      methylation of DOPAC. In conclusion, our results suggest that cyclosporin
      increases catecholamine release from the sympathetic nervous endings by a
      tyramine-like effect, i.e. by acting directly on the catecholamine transporter of
      the membrane.

PMID- 12526859
TI  - An assessment of fructose-1,6-bisphosphate as an antimicrobial and anti
      inflammatory agent in sepsis.
AB  - Tissue lesion mechanisms provoked by sepsis include the infectious process,
      inflammation, and cellular energy deficit. We chose to test fructose-1,6
      bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial
      actions. Wistar rats were used and divided into three experimental groups: a
      control group (n=10), in which a capsule was introduced into the peritoneum of
      the animals; a septic group (n=10), in which a capsule containing non-sterile
      fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and
      a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed
      that levels of leukocytes increased significantly in the septic group when
      compared to both the septic group treated with FBP and the control group. The
      blood cultures were 100% positive in both the septic group and the septic group
      treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory
      halo in the case of the antibiotic ampicillin, there was no such indication for
      FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that
      received the carrageenan injection. What is more, the sugar reduced the levels of
      ionic calcium in relation to the control group. This data proves the validity of
      using FBP in the treatment of sepsis, possibly due to its anti-inflammatory
      rather than antimicrobial action.

PMID- 12526860
TI  - Synthesis of cetyl myristoleate and evaluation of its therapeutic efficacy in a
      murine model of collagen-induced arthritis.
AB  - Cetyl myristoleate (CM) was reported by Diehl and May [J Pharm Sci 83 (1994) 296]
      to block inflammation and prevent adjuvant-induced arthritis in rats. To verify
      this earlier work, we have synthesized pure CM and tested its anti-arthritic
      properties in a collagen-induced arthritis model in DBA/1LacJ mice. Multiple
      intraperitoneal injections of CM in 450 and 900 mg kg(-1) doses resulted in a
      significantly lower incidence of disease and caused a modest but significant
      diminution in clinical signs in those mice that developed arthritis. CM
      administered in daily oral doses of 20 mg kg(-1) also reduced the incidence of
      arthritis and caused a small reduction in the clinical signs in mice that
      developed arthritis. Although the protective effect of CM in collagen-induced
      arthritis observed in the present study was less dramatic than that reported
      earlier, our results confirm the anti-arthritic properties of pure CM.

PMID- 12526861
TI  - Study of anti-inflammatory activity of Tibetan mushroom, a symbiotic culture of
      bacteria and fungi encapsulated into a polysaccharide matrix.
AB  - Tibetan mushroom (TM) is a fermented beverage composed by a dozen of bacteria and
      yeasts living together into polysaccharide grains secreted by them. TM is similar
      to kefir, a probiotic beverage originated in the Caucasian mountains exhibiting
      some anti-bacterial, anti-mycotic, anti-neoplastic and immunomodulatory effects.
      Aiming to evaluate a plausible anti-inflammatory property of TM we conducted
      cotton-induced granuloma and paw edema assays in rats, the latter using
      carrageenin, dextran and histamine as stimuli. TM samples were thawed and
      continuously cultured during 15 days into molasses solutions (50 g/l). The
      experiments used TM suspensions after 24h fermentation and TM grains mechanically
      disintegrated. The results showed a significant inhibition on the formation of
      granuloma tissue for the test group as compared to the negative control group. TM
      suspensions presented an inhibition of 43% for the inflammatory process. Rat paw
      edema also showed significant decreases with the mediators. The edema induced by
      carrageenin was inhibited 62% at the 3rd hour. The edema dextran-induced was
      completely inhibited at 1h and antagonized the histamine edema 52% at 1h.

PMID- 12526862
TI  - Intravenous administration of the food-derived opioid peptide gluten exorphin B5
      stimulates prolactin secretion in rats.
AB  - Gluten Exorphin B5 (GE-B5) is a food-derived opioid peptide, identified in vitro
      in enzymatic digests of wheat gluten. It has been suggested that this peptide may
      play a regulatory role on pituitary secretion, since it stimulates prolactin
      (PRL) secretion when administered in the cerebral ventricles in rats. It is not
      known, however, if GE-B5 can exert this stimulatory action after peripheral
      administration. In order to clarify this aspect, we gave the following treatments
      to four groups of male rats: intravenous (i.v.) vehicle, GE-B5 3 mg/kg body
      weight i.v., naloxone intraperitoneally (i.p.) followed by vehicle i.v., naloxone
      i.p. followed by GE-B5 i.v. Blood samples for PRL were taken at intervals for 60
      min after vehicle or GE-B5 administration. At the dose of 3 mg/kg body weight, GE
      B5 induced a significant increase in PRL levels; naloxone completely abolished
      any effect of GE-B5 on PRL secretion. The present study indicates that GE-B5
      stimulates PRL secretion after peripheral administration and that its action is
      mediated via classical opioid receptors; moreover, it identifies the minimum
      peptide dose which must reach the blood in order to exert its action on PRL
      secretion.

PMID- 12526863
TI  - Role of nitric oxide in the ventrolateral medulla on cardiovascular responses and
      glutamate neurotransmission during mechanical and thermal stimuli.
AB  - We have previously reported that alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA)-receptor blockade within the rostral ventrolateral medulla
      (RVLM) attenuates cardiovascular responses and extracellular concentrations of
      glutamate during mechanical, but not during thermal stimulation [Pharmacol. Res.
      43 (2001) 47]. In this study, we examined the role of nitric oxide (NO) within
      the RVLM on cardiovascular responses and glutamate release during both mechanical
      and thermal nociception using anesthetized Sprague-Dawley rats. Two types of
      stimuli were studied, both activating peripheral Adelta and C fiber polymodal
      nociceptors. Noxious mechanical stimuli were given by applying a bilateral
      hindpaw pinch for 5s. The noxious thermal stimuli were generated by immersing the
      metatarsus of both hindpaws in a water bath at a temperature of 52 degrees C for
      5s. Mechanical stimulation of both hindlimb extremities increased mean arterial
      pressure (MAP), heart rate (HR), and extracellular fluid glutamate by 14+/-2
      mmHg, 35+/-5 bpm, and 1.4+/-0.3 ng/5 microl, respectively (n=8). Similar
      responses were observed following thermal stimulation: 40+/-4 mmHg, 44+/-6 bpm,
      and 0.97+/-0.2 ng/5 microl (n=8). Bilateral microdialysis of L-arginine (1.0
      microM), a nitric oxide precursor, into the RVLM had no effects on MAP, HR, and
      glutamate increases during mechanical stimulation. However, L-arginine attenuated
      these responses during thermal nociception. Subsequent administration of L-NMMA
      (1.0 microM), a NOS inhibitor, reversed the attenuations. These results show that
      nitric oxide most likely plays a role in modulating cardiovascular responses by
      altering glutamate concentrations within the RVLM during thermal but not
      mechanical nociception. Overall, the present study delineates the differential
      central integrative mechanisms that regulate processing of sensory impulses
      arising from peripheral stimulation.

PMID- 12526864
TI  - Swainsonine stimulates bone marrow cell proliferation and differentiation in
      different strains of inbred mice.
AB  - The immunomodulatory alkaloid swainsonine (8alphabeta-indolizidine
      1alpha,2alpha,8beta-triol) has potential for overcoming the bone marrow
      suppressive effects of cancer chemotherapeutic drugs and radiation. The effect of
      swainsonine on bone marrow cellularity was evaluated in four different strains
      (C57BL/6; C3H-HEN; Balb/C and DBA-2 mice) of inbred mice subjected to multiple
      doses of the alkaloid. Swainsonine treatment stimulated bone marrow cell
      proliferation in all strains of mice. Examination of the peripheral blood did not
      reveal any increase in total leukocyte count. In vitro assessment of total colony
      forming unit (CFU) capacity of bone marrow cells showed a two- to eight-fold
      increase in swainsonine treated mice of different strains compared to their
      corresponding controls given sham injections of physiological saline. Swainsonine
      induced increase in CFU capacity of bone marrow cells should find clinical
      application in cancer treatment with chemotherapeutic agents and radiation.

PMID- 12526865
TI  - Effects of ammonium metavanadate on fertility and reproductive performance of
      adult male and female rats.
AB  - Vanadium is a ubiquitous trace metal present in most plant and animal tissues.
      Environmental exposure to trivalent and pentavalent inorganic vanadium compounds
      has been related to impaired different phases of reproduction. Therefore, the
      effects of a pentavalent inorganic vanadium compound on general reproductive
      performance and fertility were investigated in male and female rats. Sexually
      mature male and female rats were exposed to 200 ppm ammonium metavanadate in
      drinking water. Male rats were exposed for 70 days, while the female rats exposed
      for 14 days premating, during mating, and throughout the whole length of
      gestation and lactation periods till weaning. The effects on male sex organ
      weights and fertility were evaluated at the end of exposure period. However, the
      effects on female fertility as well as developmental and postnatal effects were
      evaluated throughout the exposure period. The fertility was significantly reduced
      in both treated groups, with more pronounced suppressive effects in the male
      treated group. The number of implantation sites and the number of viable fetuses
      were significantly reduced in pregnant females of both treated groups. However,
      the number of resorptions, dead fetuses, and pre- and postimplantation losses
      were significantly increased. The incidence of resorptions was significantly
      increased in treated female group compared with untreated female group. The
      behavioral responses as well as fetal survival and viability indices were
      decreased in both treated groups during the lactation period. The incidence of
      these effects was more pronounced in the treated female group. The morphological,
      visceral, and skeletal anomalies were recorded significantly increased in fetuses
      of both treated groups, with more pronounced effects on fetuses of treated
      females. In conclusion, the exposure of adult male and female rats to ammonium
      metavanadate would cause adverse effects on fertility and reproduction.

PMID- 12526866
TI  - Effects of liquid and freeze-dried grapefruit juice on the pharmacokinetics of
      praziquantel and its metabolite 4'-hydroxy praziquantel in beagle dogs.
AB  - Grapefruit juice changes the pharmacokinetic parameters of a variety of drugs
      metabolized primarily by cytochrome P450 3A. In a three-phase crossover study,
      six male beagle dogs were administered 100 ml of water (control), 100 ml of
      commercial liquid grapefruit juice, or 10 g of freeze-dried grapefruit juice
      (equivalent to 100 ml of liquid grapefruit juice) with 100 ml of water, followed
      after 2 h by single oral dose of praziquantel (30 mg kg(-1)). After treatment,
      the dogs were sampled at different times. Determination of praziquantel and its
      metabolite 4'-hydroxy praziquantel (identified by GC/MS) was performed by HPLC.
      Liquid and freeze-dried grapefruit juice preadministration increased the C(max)
      of praziquantel about three-fold and the AUC 2.5- and 2.3-fold, respectively. The
      T(max) (0.75 h) was unaffected by liquid or freeze-dried grapefruit juice, while
      T(1/2) was 2.3- and 1.7-fold higher compared with controls. The amount of 4'
      hydroxy praziquantel was also affected by both liquid and freeze-dried grapefruit
      juice administration: the AUC and C(max) increased four- and three-fold,
      respectively and the T(max) was significantly enhanced. These findings
      demonstrate that both freeze-dried grapefruit juice and commercial liquid
      grapefruit juice significantly increase plasma concentrations and T(1/2) of
      praziquantel in dogs.

PMID- 12526867
TI  - Gastroprotective effects of a crude extract of Baccharis illinita DC in rats.
AB  - Baccharis illinita DC (Compositae) is used in folk medicine to treat gastric
      disorders. The crude hydroalcoholic extract of leaves and stems tested on mice at
      doses from 1.0 to 6.0 g/kg, PO, did not produce signs of toxicity. Only the
      aqueous extract of leaves (0.1 g/kg, PO) increased intestinal motility in mice.
      The crude hydroalcoholic extract of stems and leaves (HESL) protected rats
      against lesions induced by ethanol or restraint-in-cold. The crude aqueous
      extract of roots protected against ulcers induced by ethanol, indomethacin or
      restraint-in-cold, and the crude aqueous extract of flowers only protected
      against lesions induced by ethanol. When injected into the duodenal lumen, the
      aqueous root extract inhibited basal acid secretion in pylorus-ligated rats. The
      results obtained in the present pharmacological assays indicate that this plant
      has a protective action against gastric lesions of the mucosa involving the
      maintenance of protective factors such as mucus, bicarbonate and blood flow,
      besides the reduction of gastric acid secretion.

PMID- 12526868
TI  - Providing care for critically ill children and young people--what are the
      challenges?

PMID- 12526869
TI  - Non-invasive BiPAP--implementation of a new service.
AB  - Non-invasive ventilation has been shown to be an effective treatment for acute
      hypercapnic respiratory failure. It is now increasingly used in the treatment of
      acute hypoxemic respiratory failure. National guidelines published by the British
      Thoracic Society state that facilities for NIV should be available 24 hours per
      day in all hospitals likely to admit such patients. If an acute NIV service is
      not provided, the shortage of Intensive Care beds means that some patients will
      die because facilities to invasively ventilate are not available. Conversely,
      results of a survey performed by the indicate that at the time of data
      collection, only 48% of United Kingdom hospitals provided an acute NIV service.
      The BiPAP Vision (Respironics Inc.) offers Continuous Positive Airway Pressure
      (CPAP), Bi-level Spontaneous/Timed and Proportional Assist Ventilation/Timed
      modes and is ideal for use in a critical care environment. This article presents
      some of the issues surrounding NIV, the impact of a new service, and the process
      of implementing NIV within a critical care setting.

PMID- 12526870
TI  - Leaving the intensive care unit: a phenomenological study of the patients'
      experience.
AB  - Discharge from intensive care (ICU), is said to pose difficulties for patients; a
      phenomenon referred to as "relocation stress". However, this phenomenon has not
      been fully examined, particularly from the critical care patients' perspective.
      This study, therefore, explored the lived experience of transfer from ICU to the
      ward. Phenomenology, based on the interpretative Heideggerian approach was used
      to guide the study. A purposive sample of six participants was selected. Open
      interviews were used to collect data. Participants were interviewed twice; once
      in ICU, prior to transfer, and once in the ward following transfer. The findings
      revealed that pre-transfer, participants were mainly accepting of their impending
      transfer. Participants discussed a desire for normality and identified that
      leaving the ICU staff was the most negative component of transfer. In the post
      transfer period, findings revealed mixed feelings regarding the actual transfer.
      Participants were still suffering from physical complaints, which led to feelings
      of despondency. Differences between ICU and the ward were also highlighted.
      Finally, the enormity of the ICU experience appeared to have an impact post
      transfer. The results of this study indicate that transfer from ICU can be
      problematic for some individuals. However, caution is required regarding the use
      of the nursing diagnosis of relocation stress without obtaining an individual
      perspective on experiences. Recommendations include the need for greater
      continuity of care for those recovering from critical illness.

PMID- 12526871
TI  - Developing a pain assessment tool for use by nurses in an adult intensive care
      unit.
AB  - Critically ill patients are particularly vulnerable to pain, patient's citing it
      as their second greatest ICU stressor. Pain has also been identified as a
      complicating factor in critical illness. Despite this, pain management is often
      not considered a priority by the ICU team. Effective management can only be
      achieved with accurate pain assessment. However, this is difficult in the
      critically ill as patients are often unable to communicate verbally due to the
      presence of endotracheal/tracheostomy tubes, sedation and paralysing agents.
      Nurses therefore rely on behavioural and physiological indicators in establishing
      the presence of pain. However, as these also occur in situations and conditions
      not associated with pain there is a need for a systematic, objective assessment
      tool. Such a tool, consisting of a numerical and verbal rating scale to
      facilitate documentation and audit, was developed as a result of ongoing
      adjustment and evaluation. The tool scores the patient's pain by incorporating
      behavioural and physiological indicators and is used in conjunction with the
      Glasgow Coma Score and the modified Sheffield Sedation Scale to achieve a
      comprehensive neurological assessment. As movement and intervention may
      exacerbate pain, assessment is carried out at rest and during procedures such as
      suctioning and manual handling. As an aid to pain assessment and management a
      flow chart and a clinical guideline have also been introduced. Although
      preliminary evaluation established the effectiveness of the tool as a means of
      estimating and recording pain levels in individual patients, it was evident that
      there has been no change to the way in which pain is managed. To address this
      issue, the level of nurses understanding regarding pain management has been
      ascertained and teaching sessions delivered to increase the profile of pain
      management in the unit.

PMID- 12526872
TI  - Patients' interpretation of the symptoms of myocardial infarction: implications
      for cardiac rehabilitation.
AB  - Research has shown that patients' models of illness are likely to be different
      from those of health professionals and that these beliefs may be more important
      than medical factors in directing the recovery process. Beliefs about myocardial
      infarction may influence coping with the illness, expectations for recovery,
      patients' reactions to subsequent cardiac events, morbidity and compliance rates
      and attendance at rehabilitation courses. This qualitative study explores
      patients' interpretation of the symptoms of myocardial infarction and their
      personal theories about the illness. Data collection was undertaken in a coronary
      care unit, using semi-structured interviews with 50 patients. Ethnographic
      content analysis was used to develop an insightful description of commonalties in
      the data. Major categories from the data included: providing a historical
      context, the metaphor of a heart attack, labelling of symptoms and making sense
      of the illness experience. Interventions to increase participation in
      rehabilitation programmes need to take into consideration patients' theories
      about their illness.

PMID- 12526873
TI  - Remifentanil.
AB  - Remifentanil is a synthetic opioid receptor agonist that was introduced in 1997
      for analgesia during general anaesthesia. However, it recently received a license
      for analgesia and sedation in ventilated intensive care patients and so is now of
      interest to those working in intensive care.

PMID- 12526874
TI  - Factors influencing bactericidal activity of blue mussel (Mytilus edulis)
      haemocytes against Salmonella typhimurium.
AB  - This study showed that in vitro survival of Salmonella typhimurium, after
      exposure to haemocytes of Mytilus edulis, was significantly affected by the
      lipopolysaccharides (LPS) structures expressed on the cell surface of the
      bacteria. Survival seemed to be affected by the surrounding temperature as well.
      Mussel haemocytes were in vitro exposed to mutants of S. typhimurium, expressing
      differences in O -antigen polysaccharide chains and core sugars of LPS on their
      cell surface. Surviving cells of the mutants were determined after incubation
      with the haemocytes at different temperatures, using a colorimetric assay. In
      addition, a complementary study on clearance of these mutants, inoculated into
      the adductor muscle of mussels, was performed at 6 and 20 degrees C. It was
      concluded that the survival index (SI%) measured in vitro for the mutant with
      complete LPS was significantly lower at 6 degrees C (c.15%) compared to that at
      14 and 20 degrees C (c.70%). SI% for the other mutants was c.35-45% and was not
      affected by temperature. The in vivo study at 20 degrees C showed that during the
      first 24h, the clearance rate for the mutants with complete LPS was significantly
      higher than for the others. Thereafter all mutants, with exception for the most
      deficient, started to increase in numbers and caused death to the mussels. At 6
      degrees C the mutants were slowly reduced and after 17 days, viable cells of the
      mutant with complete LPS were still detectable in the haemolymph. The study
      indicated that the mussel haemocytes responded in relation to the LPS of the
      mutants. However, more intact LPS also seemed to protect the bacteria from being
      killed. The higher temperatures favoured the growth of the mutants that managed
      to resist the haemocyte defence. Cell surface properties and temperature seem to
      affect the survival of bacteria in mussels, which consequently can affect risk
      assessments in regard to public health.

PMID- 12526875
TI  - In the spiny lobster (Panulirus interruptus) the prophenoloxidase is located in
      plasma not in haemocytes.
AB  - In the spiny lobster (Panulirus interruptus), unlike other crustaceans most of
      the prophenoloxidase (proPO) was detected in cell-free plasma (86.3%). In spite
      of its location, lobster proPO activating system has a similar activation
      mechanism to other crustacean proPO systems. Haemocyte lysate was able to
      activate the plasma proPO indicating location of the prophenoloxidase activating
      enzyme (PPAE) in haemocytes. Lobster haemocyte PPAE was isolated by affinity
      chromatography and its participation as activating enzyme was demonstrated. This
      enzyme is a serine-proteinase that transforms the inactive form (proPO) to an
      active one (phenoloxidase). The PPAE was also present in the cell-free
      supernatant of haemocytes previously incubated with Vibrio alginolyticus.

PMID- 12526876
TI  - Production of rabbit antisera against recombinant MHC class II beta chain and
      identification of immunoreactive cells in Atlantic salmon (Salmo salar).
AB  - In the present work, rabbit antisera recognising the Atlantic salmon (Salmo
      salar) MHC class II beta chain polypeptide were produced and used in
      immunoblotting, immunohistochemistry and immunogold electron microscopy. A
      construct encoding the beta1 and beta2 domains fused to the E. coli protein
      thioredoxin was used to express the recombinant MHC class II beta chain.
      Immunoblotting revealed a band of approximately 30kDa in total protein samples
      from head kidney, spleen, gills, thymus and blood leukocytes, while being absent
      in muscle. The distribution of MHC class II positive cells was
      immunohistochemically demonstrated in Atlantic salmon epithelial and haemopoietic
      tissues. Ultrastructural demonstration of immunoreactive organelles in mid-kidney
      cells was performed by immunogold electron microscopy. The results indicate
      expression in lymphocytes, macrophages, epithelial cells and endritic-like cells.
      This is the first study to address morphological MHC class II expression in a
      fish species.

PMID- 12526877
TI  - Tumouricidal activity of gilthead seabream (Sparus aurata L.) natural cytotoxic
      cells: the role played in vitro and in vivo by retinol acetate.
AB  - The natural cytotoxic activity of gilthead seabream head-kidney leucocytes was
      evaluated after in vitro incubation with retinol acetate as vitamin A source, and
      in samples taken from specimens receiving an intraperitoneal injection or a diet
      supplemented with this vitamin. Isolated leucocytes were incubated with 0 to 10(
      10)m all-trans-retinol acetate-supplemented culture medium for 0, 6 or 24h and
      assayed for their tumouricidal activity which was found to increase for all the
      assayed concentrations and incubation times. Seabream specimens were
      intraperitoneally injected with 0 (control), 1.75 or 5.25 micro g retinol acetate
      100 g(-1) biomass and sampled 1, 3 or 5 days post-injection. Leucocyte natural
      cytotoxic activity increased in a dose-dependent manner 1 and 3 days post
      injection. When fish were fed a commercial diet supplemented with 0 (control),
      50, 150 or 300 mg retinol acetate kg(-1) diet for 1, 2, 4 or 6 weeks, only fish
      which had been fed the highest supplement for 2 weeks showed any increase in head
      kidney leucocyte cytotoxic activity. Serum was isolated and analysed for all
      trans-retinol concentration by reverse-phase high-pressure-liquid-chromatography.
      The normal level was about 0.4 micro g ml(-1) serum, while treatment for 1 to 4
      weeks with vitamin A increased this level. In conclusion, retinol acetate
      increases gilthead seabream head-kidney leucocyte cytotoxic activity both in
      vitro and in vivo.

PMID- 12526878
TI  - The effect of dietary intake of vitamins C and E on the stress response of
      gilthead seabream (Sparus aurata L.).
AB  - High dietary doses of the antioxidant vitamins C and E were administered to
      gilthead seabream (Sparus aurata L.) in an attempt to reduce the stress response
      in specimens exposed to a multiple stress situation. Fish were fed four different
      diets for 6 weeks: a commercial feed containing 0.1g vitamin C and 0.1g vitamin E
      kg(-1) acted as control diet, while experimental diets consisted of the same feed
      supplemented with 3g vitamin C kg(-1), 1.2g vitamin E kg(-1) or both 3g vitamin C
      and 1.2g vitamin E kg(-1). After 2, 4 and 6 weeks fish were exposed to stressors
      typical of aquacultural practices, and serum cortisol levels, complement activity
      (measured by the alternative pathway), blood glucose level and respiratory burst
      activity of head-kidney leucocytes were evaluated. The results showed that all
      stress-induced increases in blood glucose concentration were lower in fish fed
      the vitamin C and/or E-supplemented diet than in fish fed the control diet after
      2 weeks of treatment, although no other differences were found at the rest of the
      times. Cortisol levels increased in stressed fish and did not suffer depletion as
      a consequence of administering vitamins C and/or E as a supplement. The natural
      haemolytic complement activity was not affected by the stressors but enhanced in
      specimens fed vitamin-supplemented diets at week 6. The respiratory burst
      activity was depressed by the stressors in fish fed the control diet, although
      only after 6 weeks of treatment were the differences statistically significant.
      These results suggest that vitamins C and E are involved in the hypothalamic
      sympathetic-chromaffin cell axis and also interfere in tertiary stress responses
      such as immunodepression, where they protect the leucocyte functions.

PMID- 12526879
TI  - Immunomodulatory effects of nisin in turbot (Scophthalmus maximus L.).
AB  - In the present work, the effect of nisin on the non-specific immune response of
      turbot (Scophthalmus maximus L.) leukocytes has been studied both in vitro and in
      vivo. The head kidney macrophage chemiluminescent (CL) response was significantly
      increased with intermediate doses of nisin (2.5 and 0.025 micro g ml(-1)) whilst
      the higher dose (25 micro g ml(-1)) significantly decreased the response after
      24h incubation. When the incubation time was extended to 72 h, significant
      differences between doses were observed and the lower nisin concentration (0.025
      micro g ml(-1)) appeared to be the optimum dose for increasing the CL response.
      The phagocytic activity of HK macrophages was also affected by in vitro nisin
      treatments. Nisin at 0.25 micro g ml(-1) and 0.025 micro g ml(-1) significantly
      stimulated the response after 24 and 72 h incubation respectively. Nitric oxide
      (NO) production by HK macrophages was not influenced by any nisin concentration
      employed for 24 or 72 h incubationsIn vivo, one week post injection, a slightly
      but non-significant stimulation of the CL response was observed with the lowest
      nisin concentration (0.0025 micro g fish(-1)). NO in serum and serum
      antibacterial index were not significantly affected by nisin treatments. On the
      other hand, lysozyme concentration in serum was significantly augmented with the
      lowest nisin dose (0.0025 micro g fish(-1)). The antibacterial effect of nisin
      against the fish pathogenic bacteria Carnobacterium piscicola (CECT 4020) was
      also demonstrated in vitro.

PMID- 12526880
TI  - Chromosome mapping of MHC class I in rainbow trout (Oncorhynchus mykiss).
AB  - The major histocompatibility complex (MHC) is well-studied in mammals. Much
      research has addressed the genomic organisation of MHC genes and it is well
      established that human MHC class I genes are located on chromosome 6. However,
      information on the organisation of the MHC complex in rainbow trout is only
      beginning to become available. In the present study it was determined that
      rainbow trout MHC class I sequences are located on chromosome 18. This is the
      first reported use of fluorescence in situ hybridisation (FISH) to identify the
      chromosomal location of genes involved in the immune system of fish.

PMID- 12526881
TI  - The promoter of the classical MHC class I locus in rainbow trout (Oncorhynchus
      mykiss).
AB  - In rainbow trout only a single classical major histocompatibility complex (MHC)
      class I locus has been identified. In previous studies it was shown that this
      locus, Onmy-UBA, is characterised by extensive polymorphism and ubiquitous
      expression. In the present study the sequence of the promoter region of Onmy-UBA
      was analysed. Within this region several fragments for transcription regulation
      could be detected, including interferon-sensitive enhancer elements. The promoter
      region is very similar to that of classical MHC class I in higher vertebrates. In
      agreement with the interferon sensitive elements identified in its promoter, Onmy
      UBA expression in rainbow trout gonad cells (RTG-2 cell line) was up-regulated
      after infection with infectious haematopoietic necrosis virus (IHNV).

PMID- 12526882
TI  - Expression of members of the S100 Ca2+-binding protein family in guinea-pig
      smooth muscle.
AB  - The calcium-binding proteins of the S100 family show tissue-specific expression.
      In this study, the mRNA and protein expression of five S100 calcium-binding
      proteins was investigated in different guinea-pig smooth muscle preparations.
      Transcripts of cDNA of S100A1, S100A4, S100A6 and S100A10 were amplified from
      smooth muscle RNA of neonatal and adult urinary bladder, ileum, aorta and from
      freshly isolated and cultured urinary bladder smooth muscle cells. S100B was not
      detectable in smooth muscle RNA, but was seen in control RNA isolated from brain.
      The pattern of S100 mRNA expression did not change during postnatal development
      and cell culture of smooth muscle. The structural homology of guinea-pig S100
      proteins reverse transcription-polymerase chain reaction (RT-PCR) sequences
      compared to other species was 85-93% (human), 83-88% (rat) and 81-87% (mouse).
      Protein expression of S100A4, S100A6 and S100A10 was investigated in aorta,
      ileum, bladder and cultured bladder smooth muscle cells by Western blot analysis
      using polyclonal antibodies against guinea-pig-specific S100 immunogenic peptide
      sequences raised in rabbits. The results show that the proteins S100A4, S100A6
      and S100A10 are expressed in the smooth muscle of ileum, bladder and aorta.
      S100A4 and S100A6 proteins are also expressed in cultured smooth muscle cells.
      The results of this study suggest that the calcium-binding proteins S100A1,
      S100A4, S100A6 and S100A10, but not S100B, are expressed in guinea-pig smooth
      muscle, and could be potentially involved in the regulation of cytoplasmic Ca(2+)
      concentration and/or in signal transduction in smooth muscle.

PMID- 12526883
TI  - Calcium ionophore and phorbol ester increase membrane binding of annexin a7 in
      alveolar type II cells.
AB  - The fusion of lamellar body with plasma membrane, a distal obligatory step in
      exocytosis of lung surfactant, may be mediated by annexin a7 (anx a7; synexin).
      To understand the mechanism of anx a7 action, we tested the hypothesis that anx
      a7 binding to membranes would increase in order to facilitate membrane fusion
      during stimulation of lung surfactant secretion. Isolated rat alveolar type II
      cells were treated with established secretagogues of lung surfactant and the
      membrane and cytosol fractions were analyzed for in vitro binding of anx a7. In
      cells treated with calcium ionophore (A23187) or phorbol 12-myristate 13-acetate
      (PMA), anx a7 binding to the membrane fraction was increased by 120%, while that
      to the cytosol fraction was decreased by 40%, when compared with binding to
      corresponding fractions from control cells. Protein kinase inhibitors prevented
      the PMA effects on anx a7 binding. The lamellar body and plasma membrane
      fractions of A23187-treated cells also showed increased binding of anx a7. The
      lamellar bodies of A23187-treated cells showed lower K(m) for Ca(2+) and higher
      maximal binding of anx a7, when compared with those from control cells.
      Collectively, our findings suggest that these two agents modify membrane proteins
      to regulate anx a7 binding, which may facilitate increased membrane fusion
      activity during stimulation of surfactant secretion.

PMID- 12526884
TI  - Homogeneous Ca2+ stores in rat adrenal chromaffin cells.
AB  - The localization and function of Ca(2+) stores in isolated chromaffin cells of
      rat adrenal medulla were investigated using confocal laser microscopy and
      amperometry. Binding sites for BODIPY-inositol 1,4,5-trisphosphate (IP(3)), 
      ryanodine (Ry), and -thapsigargin (Thap) were both perinuclear and at the cell
      periphery. The endoplasmic reticulum (ER), which was identified by ER Tracker
      dye, took up fluorescent Ry and IP(3), and the majority of BODIPY-Ry-binding area
      was bound by fluorescent IP(3). Under Ca(2+)-free conditions, the amount of
      caffeine-induced catecholamine secretion was 33% of that of muscarine-induced
      secretion, but muscarine induced little or no secretion after exposure to
      caffeine. Muscarine-induced Ca(2+) increases, as observed with fluo-3, lasted for
      a few tens of seconds under Ca(2+)-free conditions, whereas a caffeine-induced
      Ca(2+) transient diminished rapidly with a half decay time of 3s and this spike
      like Ca(2+) transient was then followed by a sustained increase with a low level.
      These results indicate that IP(3) receptors and Ry receptors (RyRs) are present
      in common ER Ca(2+) storage and the lower potency of caffeine for secretion may
      be due to a rapid decrease in RyR channel activity to a low level.

PMID- 12526885
TI  - Fura-2 antagonises calcium-induced calcium release.
AB  - Calcium-induced calcium release (CICR) from the endoplasmic reticulum (ER) takes
      place through ryanodine receptors (RyRs) and it is often revealed by an increase
      of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) induced by caffeine. Using
      fura-2-loaded cells, we find such an effect in bovine adrenal chromaffin cells,
      but not in cerebellar granule neurones or in HEK-293 cells. In contrast, a
      caffeine-induced [Ca(2+)](c) increase was clearly visible with either fluo-3 or
      cytosolic aequorin. Simultaneous loading with fura-2 prevented the [Ca(2+)](c)
      increase reported by the other Ca(2+) probes. Caffeine-induced Ca(2+) release was
      also measured by following changes of [Ca(2+)] inside the ER ([Ca(2+)](ER)) with
      ER-targeted aequorin in HEK-293 cells. Fura-2 loading did not modify Ca(2+)
      release from the ER. Thus, fura-2, but not fluo-3, antagonises the generation of
      the cytosolic Ca(2+) signal induced by activation of RyRs. Cytosolic Ca(2+)
      buffering and/or acceleration of Ca(2+) diffusion through the cytosol may
      contribute to these actions. Both effects may interfere with the generation of
      microdomains of high [Ca(2+)](c) near the ER release channels, which are
      essential for the propagation of the Ca(2+) wave through the cytosol. In any
      case, our results caution the use of fura-2 to study CICR.

PMID- 12526886
TI  - Photoliberating inositol-1,4,5-trisphosphate triggers ATP release that is blocked
      by the connexin mimetic peptide gap 26.
AB  - Calcium signals can be communicated between cells by the diffusion of a second
      messenger through gap junction channels or by the release of an extracellular
      purinergic messenger. We investigated the contribution of these two pathways in
      endothelial cell lines by photoliberating InsP(3) or calcium from intracellular
      caged precursors, and recording either the resulting intercellular calcium wave
      or else the released ATP with a luciferin/luciferase assay. Photoliberating
      InsP(3) in a single cell within a confluent culture triggered an intercellular
      calcium wave, which was inhibited by the gap junction blocker alpha
      glycyrrhetinic acid (alpha-GA), the connexin mimetic peptide gap 26, the
      purinergic inhibitors suramin, PPADS and apyrase and by purinergic receptor
      desensitisation. InsP(3)-triggered calcium waves were able to cross 20 microm
      wide cell-free zones. Photoliberating InsP(3) triggered ATP release that was
      blocked by buffering intracellular calcium with BAPTA and by applying gap 26. Gap
      26, however, did not inhibit the gap junctional coupling between the cells as
      measured by fluorescence recovery after photobleaching. Photoliberating calcium
      did not trigger intercellular calcium waves or ATP release. We conclude that
      InsP(3)-triggered ATP release through connexin hemichannels contributes to the
      intercellular propagation of calcium signals.

PMID- 12526887
TI  - Evidence for a modulatory effect of external potassium ions on ionic current
      mediated by the cardiac Na+-Ca2+ exchanger.
AB  - The aim of this study was to investigate whether or not the activity of the
      cardiac Na(+)-Ca(2+) exchanger might be directly sensitive to external K(+)
      concentration ([K(+)](e)). Measurements of whole-cell exchanger current (I(NaCa))
      were made at 37 degrees C from guinea-pig isolated ventricular myocytes, using
      whole-cell patch clamp recording with major interfering conductances blocked.
      Changing [K(+)](e) from 0 to 5mM significantly reduced both outward and inward
      exchange currents in a time-dependent manner. Various [K(+)](e) between 1 and 15
      mM were tested and the inhibitory effect was observed to be concentration
      dependent. At steady-state, 5mM [K(+)](e) decreased the density of Ni(2+)
      sensitive current by 52.8+/-4.3% (mean+/-S.E.M., n=6) and of 0Na0Ca-sensitive
      current by 39.0+/-4.4% (n=5). The possibility that the inhibitory effect of
      external K(+) on I(NaCa) might wholly or in part be secondary to activation of
      the sarcolemmal Na(+)-K(+) pump was investigated by testing the effect of K(+)
      addition in the presence of a high concentration of strophanthidin (500 microM).
      Ni(2+)-sensitive I(NaCa) was still observed to be sensitive to external K(+)
      (I(NaCa) decreased by 39.4+/-9.4%, n=4), suggesting that the inhibitory effect
      could occur independently of activation of the Na(+)-K(+) pump. The effect of
      external K(+) on I(NaCa) was verified using a baby hamster kidney (BHK) cell line
      stably expressing the cardiac Na(+)-Ca(2+) exchanger isoform, NCX1. Similar to
      native I(NaCa), NCX1 current was also suppressed by [K(+)](e). However, [K(+)](e)
      did not alter current amplitude in untransfected BHK cells. The effect of
      [K(+)](e) on I(NaCa) could not be attributed to simply adding any monovalent
      cation back to the external solution, since it was not reproduced by application
      of equimolar Li(+), Cs(+) and TEA(+). Rb(+), however, could mimic the effect of
      K(+). Collectively, these data suggest that external K(+) at physiologically and
      pathologically relevant concentrations might be able to modulate directly the
      activity of the cardiac Na(+)-Ca(2+) exchanger.

PMID- 12526888
TI  - Disturbances in purinergic [Ca2+]i signaling pathways in a transformed rat
      thyroid cell line.
AB  - It was previously shown that in rat thyroid PC-Cl3 cell line, a purinergic P2Y
      receptor increases the concentration of free cytosolic Ca(2+) ([Ca(2+)](i)) via
      phospholipase C activation. We here studied whether in a transformed cell line
      (PC-E1Araf) derived from parental PC-Cl3 cells, ATP is still able to transduce
      the [Ca(2+)](i)-based intracellular signal.We demonstrate the expression of mRNA
      for P2Y2 in both PC-Cl3 and PC-E1Araf cells; mRNAs for P2Y1, P2Y4, P2Y6 and P2Y11
      were absent. In both cell lines activation of P2Y2 receptor provokes a transient
      increase in [Ca(2+)](i) followed by a lower sustained phase persisting for over
      5min in PC-Cl3 and only 1.5 min in PC-E1Araf cells. In both cell lines the
      [Ca(2+)](i) reached a plateau level significantly higher than the basal
      [Ca(2+)](i) level persisting for over 10 min. Removal of extracellular Ca(2+)
      reduced the initial transient response to ATP in PC-Cl3, but not in PC-E1Araf
      cells, and completely abolished the plateau phase in both cell lines. In the
      presence of extracellular Ca(2+) thapsigargin (TG) caused a rise in [Ca(2+)](i)
      significantly higher in PC-Cl3 than transformed PC-E1Araf cells, while in Ca(2+)
      free medium the effect of TG was similar in both cell lines. The capacitative
      Ca(2+)-entry in PC-Cl3 resulted significantly higher than in PC-E1Araf cells.
      Further studies were performed in order to investigate whether the different
      effects of ATP on [Ca(2+)](i) was due to variation in divalent cation plasma
      membrane permeability. PC-E1Araf cells showed a much lower permeability to
      Ca(2+), Ba(2+), Sr(2+), Mn(2+), and Co(2+) that may be responsible for the
      differences in purinergic Ca(2+) signaling pathway with respect to parental PC
      Cl3 cells.

PMID- 12526889
TI  - Axonal localization of delta Ca2+/calmodulin-dependent protein kinase II in
      developing P19 neurons.
AB  - Ca(2+)/calmodulin-dependent protein kinase, type II (CaMK-II) is an enzyme
      encoded by four genes (alpha, beta, gamma and delta) and traditionally associated
      with synaptic function in the adult central nervous system, but also believed to
      play a role during neuronal development. P19 mouse embryonic cells are a model
      system for neurogenesis and primarily express isozymes of delta CaMK-II. It is
      not yet known whether or where delta CaMK-II is expressed in P19 neurons. Using
      an antibody specific for the delta CaMK-II C-terminal tail, we detected a 20-fold
      increase in levels of delta CaMK-II along axons after 8 days of development. This
      coincides with increased mRNA and protein levels of delta(C) CaMK-II, which
      contains the alternative tail. This follows the initial stages of neurite
      outgrowth and beta(3) tubulin expression, which occur after 4 days. delta CaMK-II
      co-localizes with the axonal protein GAP-43, but not the dendritic microtubule
      associated protein MAP-2, a known substrate of alpha CaMK-II. Like delta CaMK-II,
      GAP-43 shows increased expression after 8 days. These findings demonstrate
      developmental regulation of the alternative C-terminal delta CaMK-II exon and
      implicate endogenous delta CaMK-II in axonal development in embryonic cells.

PMID- 12526890
TI  - D1 dopamine receptor regulation of cell cycle in FGF- and EGF-supported primary
      cultures of embryonic cerebral cortical precursor cells.
AB  - In the mammalian fetus, proliferation of the majority of cells destined for the
      cerebral cortex takes place within the transient proliferative zones of the
      cerebral wall. Recent investigations have demonstrated that cell of these zones
      express high levels of D1 dopamine receptors (D1Rs). However, the specific roles
      of these receptors have not been investigated. The present study tests the
      hypothesis that D1Rs are capable of regulating the cell cycle of cerebral
      cortical precursor cells. For this purpose, primary cultures of cells of the
      proliferative zones from the cerebral wall of 14-day-old mouse fetuses were
      generated and maintained in the presence of either fibroblast growth factor-2
      (FGF2) or epidermal growth factor (EGF). These growth factors were chosen as
      supporting two distinct populations of precursor cells in the fetal cortical
      proliferative matrix. The involvement of D1Rs in the regulation of proliferative
      activity was examined by the addition of a range of concentrations of the D1R
      specific agonist, SKF82958, to the culture media. Bromodeoxyuridine incorporation
      assays demonstrated that exposure to this agonist led to a dose-dependent
      reduction of DNA synthesis in both FGF2- and EGF-supported cultures. Flow
      cytometric cell cycle assays further revealed that this was due to prevention of
      the transition of cells from the G1 phase to the S phase of the cell cycle. The
      D1R specificity of the effects of SKF82958 was supported in that they were
      blocked by the addition of the D1R antagonists, SCH23390 or NNC010756. We also
      found that D1R stimulation induced stronger suppression of proliferative activity
      in EGF-supported than in FGF2-supported cultures. Our observations suggest that
      D1Rs are capable of regulating the cell cycle during corticogenesis. Furthermore,
      they raise a possibility that these receptors may display different efficacies in
      affecting proliferative activity in FGF2-supported versus EGF-supported cerebral
      cortical precursor cells.

PMID- 12526891
TI  - Medium requirements for neuritic outgrowth from goldfish retinal explants and the
      trophic effect of taurine.
AB  - The use of culture media of known composition are necessary for studying the role
      of trophic molecules. Since most of the in vitro research on regeneration of the
      optic nerve has been performed in the presence of fetal calf serum, the aim of
      this study was to obtain a medium in which the neuritic outgrowth from post-crush
      goldfish retinal explants could take place without adding fetal calf serum. After
      the lesion of the optic nerve (10 days), the retina of goldfish was dissected and
      explants were cultured for 5 and 10 days in the absence or in the presence of
      fetal calf serum, at which time the neuritic outgrowth was determined. Various
      concentrations and combinations of glucose, albumin, calcium, HEPES and taurine
      were used. The highest neuritic outgrowth was observed in the presence of fetal
      calf serum, in which condition the amino acid taurine increased length and
      density of neurites. Media supplemented with albumin, calcium or HEPES did not
      modify the outgrowth of neurites from the explants. However, glucose favored the
      neuritic outgrowth in a bell-shaped manner, although fibers were thinner than
      those observed in the presence of fetal calf serum. Taurine did not stimulate
      outgrowth of neurites from explants growing in a medium with optimal
      concentrations of glucose, indicating that elements of the fetal calf serum are
      determinant for the trophic effect of taurine. The present results contribute to
      further studies, such as those related to the effect of taurine and of trophic
      factors derived from the optic tectum, which would be performed in the presence
      of a medium free of fetal calf serum.

PMID- 12526892
TI  - A second source of precursor cells for the developing enteric nervous system and
      interstitial cells of Cajal.
AB  - The enteric nervous system is believed to be derived solely from the neural crest
      cells. This is partly based on the belief that the neural crest cells are the
      sole neural tube-derived cells colonizing the gastrointestinal tract. However,
      recent studies have shown that after the emigration of neural crest cells an
      additional population of cells emigrate from the cranial neural tube. These cells
      originate in the ventral part of the hindbrain, emigrate through the site of
      attachment of the cranial nerves, and colonize a variety of developing structures
      including the gastrointestinal tract. This cell population has been named the
      ventrally emigrating neural tube (VENT) cells. We followed the fate of these
      cells in the gastrointestinal tract. Ventral hindbrain neural tube cells of chick
      embryos were tagged with replication-deficient retroviral vectors containing the
      LacZ gene, after the emigration of neural crest from this region. In control
      embryos, the viral concentrate was dropped on the dorsal part of the neural tube.
      Embryos were sacrificed from embryonic days 3-12 and processed for the detection
      of LacZ positive ventrally emigrating neural tube cells. These cells colonized
      only the foregut, specifically the duodenum and stomach. Immunostaining with the
      neural crest cell marker HNK-1 showed that they were HNK-1 negative, indicating
      that they were not derived from neural crest. Cells were detected in three
      locations: (1). the myenteric and submucosal plexus of the enteric nervous
      system; (2). circular smooth muscle cell layer; and (3). mucosal lining of the
      lumen. A variety of specific markers were used to identify their fate. Some
      ventrally emigrating neural tube cells differentiated into neurons and glial
      cells, indicating that the enteric nervous system in the foregut develops from an
      additional source of precursor cells. It was also found that some of these cells
      differentiated into interstitial cells of Cajal, which mediate impulses between
      the enteric nervous system and smooth muscle cells, whereas others differentiated
      into epithelium. Altogether, these results indicate that the ventrally emigrating
      neural tube cells are multipotential. More importantly, they reveal a novel
      source of precursor cells for the neurons and glial cells of the enteric nervous
      system. The developmental and functional significance of the heterogeneous origin
      of the cell types remains to be established.

PMID- 12526893
TI  - Sexual dimorphism in rat cerebrum and cerebellum: different patterns of
      catalytically active creatine kinase isoenzymes during postnatal development and
      aging.
AB  - During postnatal development, maturation and aging the Wistar rat cerebrum and
      cerebellum synthesize, in a different sex-dependent manner, catalytically active
      dimeric cytosolic (c) muscle-type (MM) and heart-type (MB) creatine kinase (CK),
      besides the supposedly sole type brain-specific (BB) CK. In both sexes, typical
      and atypical neuromuscular cCK isoenzymes were present during the study for 26
      months. As in rat heart, females showed more cerebral cCK variants (41%) in
      comparison to males. Female rats exhibited about 93% more cerebellar variants of
      cCK isoenzymes as compared to males. The male cerebellum showed predominantly BB-
      and MB-CK during the whole study in comparison to the female one that contained
      all neuromuscular cCK variants. Only female rats showed decreases and increases
      of cerebral CK specific activity. In contrast to males, coinciding with the
      weaning period, cerebral female CK activity decreased 45% from 14 to 21 days and
      increased about 3-fold in female rats and only 1.3-fold in males from 21 to 45
      days of age. Contrary to the remarkable 4-fold increase of chicken brain CK
      specific activity exhibited at old age, the rat did not show another cerebral CK
      activity increase during senescence in either sex. However, sex differences of CK
      specific activity appeared in the cerebellum at all ages. From the sex-specific
      plateau phase at 45-60 days until 2.2 years of age, about a 41% independent
      increase of cerebellar CK specific activity was observed in both sexes. After
      puberty, the differential cerebellum-cerebrum values of CK specific activity were
      higher for female rats than males during youth, adulthood and senescence. The
      present work shows that in rat cerebrum and cerebellum, production of ATP through
      anaerobic transphosphorylation by the CK/PC system is sex-and age-specific,
      especially in the cerebellum, when glycolysis and the Krebs cycle lose capacity.
      As in rat heart, under physiological conditions at all ages the several cCK
      isoenzymes do participate in a gender-specific manner, in favor of females, in
      diverse functions of the different cell compartments of glial and neuronal cells
      with regard to their high and fluctuating energy demands not completely covered
      by anaerobic and aerobic glycolysis.

PMID- 12526894
TI  - Trace element reference values in tissues from inhabitants of the EU. XII.
      Development of BioReVa program for statistical treatment.
AB  - Statistical data treatment is a key point in the assessment of trace element
      reference values being the conclusive stage of a comprehensive and organized
      evaluation process of metal concentration in human body fluids. The EURO TERVIHT
      project (Trace Elements Reference Values in Human Tissues) was started for
      evaluating, checking and suggesting harmonized procedures for the establishment
      of trace element reference intervals in body fluids and tissues. Unfortunately,
      different statistical approaches are being used in this research field making
      data comparison difficult and in some cases impossible. Although international
      organizations such as International Federation of Clinical Chemistry (IFCC) or
      International Union of Pure and Applied Chemistry (IUPAC) have issued recommended
      guidelines for reference values assessment, including the statistical data
      treatment, a unique format and a standardized data layout is still missing. The
      aim of the present study is to present a software (BioReVa) running under
      Microsoft Windows platform suitable for calculating the reference intervals of
      trace elements in body matrices. The main scope for creating an ease-of-use
      application was to control the data distribution, to establish the reference
      intervals according to the accepted recommendation, on the base of the simple
      statistic, to get a standard presentation of experimental data and to have an
      application to which further need could be integrated in future. BioReVa
      calculates the IFCC reference intervals as well as the coverage intervals
      recommended by IUPAC as a supplement to the IFCC intervals. Examples of reference
      values and reference intervals calculated with BioReVa software concern Pb and Se
      in blood; Cd, In and Cr in urine, Hg and Mo in hair of different general European
      populations.

PMID- 12526895
TI  - Application of high Cu compost to Swiss chard and basil.
AB  - A greenhouse container experiment was conducted to evaluate the effect of high Cu
      compost on basil and Swiss chard productivity, and the accumulation of As, Ca,
      Fe, Hg, K, Mg, Na, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, S and Se in growth medium and
      plant tissue. The Cu content of the compost was over 1200 mg/kg, much higher than
      Canadian standards for type B compost quality. The treatments consisted of
      control soil (0% compost), and 20, 40 and 60% (by volume) of high Cu compost
      added to soil. All compost application treatments (20, 40 and 60%) resulted in
      increased dry matter yields in Swiss chard and basil. Addition of high Cu compost
      influenced basil plant development. Plants from the 20 and 40% treatments had
      higher numbers of buds and flowers. There were no differences between the control
      and 60% compost treatments with respect to flower initiation. Addition of 20, 40
      and 60% compost to the soil resulted in increased EXCH fractions of Cu, but not
      of Mn and Zn. Compost additions resulted in increase in the HNO(3) extractable,
      CARB, FeMnOX, and in OM fractions of Cu, Mn and Zn in soils. Compost application
      increased soil pH and EC, soil HNO(3) extractable Ca, K, Mg, P, Na, B and Pb, but
      did not alter soil HNO(3) extractable Cd, Co, Cr, Mo, Ni, Se. Increased rates of
      compost application decreased tissue Ca in basil, tissue Na in both plants,
      increased tissue K, Mg in both plants, but, did not alter tissue P, Co, Cr, Mo,
      Ni of either plants, and B in basil. Tissue As, Hg, Pb, and Se from all
      treatments were under the detection limits of VGA-AAS (for As, Hg, Se) and ICP
      (for Pb). Compost additions altered basil oil chemical composition. Copper in the
      essential oil of basil was below 0.25 mg/l. In conclusion, the addition of high
      rates of relatively immature high Cu compost may not always increase Cu
      concentration in plants and in plant oils.

PMID- 12526896
TI  - Organochlorine levels in maternal and umbilical cord blood plasma in Arctic
      Canada.
AB  - A baseline for exposure to organochlorine and metal contaminants has been
      established for mothers and newborns in the Northwest Territories and Nunavut
      areas of Arctic Canada. Maternal and umbilical cord blood plasma organochlorine
      levels are described for Inuit, Dene, Metis, Caucasian and Other non-Aboriginal
      participants. Overall, 523 women volunteered to participate by giving their
      written informed consent between May 1994 and June 1999, resulting in the
      collection of 386 maternal blood samples, 407 cord blood samples and 351
      maternal/cord pairs. Nearly half of all the participants regularly smoked
      cigarettes, including 77% of the Inuit participants. Maternal and cord results
      are presented for PCBs (as Aroclor 1260 and 14 congeners) and organochlorine
      pesticides, including p,p'-DDT, p,p'-DDE, beta-hexachlorocyclohexane (beta-HCH),
      hexachlorobenzene (HCB), cis and trans nonachlor, heptachlor epoxide,
      oxychlordane, mirex, dieldrin and toxaphene. Maternal PCB levels (as Aroclor
      1260) averaged 4.42 (+/-9.03) microg/l in Inuit, which was 3.3 times higher than
      those found in Dene/Metis, and 3.4 times higher than levels in Caucasians. Mean
      DDE levels were 2.8 times higher in the Other non-Aboriginal group (Chinese,
      Filipino, East Indian and multiple ethnicity) than in the Inuit group, at 3.99
      microg/l and 1.42 microg/l, respectively. Cord blood PCB levels (as Aroclor 1260)
      averaged 1.16 (+/-2.42) microg/l for Inuit participants, which was 3.3-4 fold
      higher than the other ethnic groups. PCBs, p,p'-DDE and hexachlorobenzene were
      detected in all maternal samples, and p,p'-DDE was detected in all cord samples.
      Regression coefficients for maternal/cord pairs are presented for selected
      organochlorines. Other results from this study, including maternal and cord
      metals data, will be presented elsewhere.

PMID- 12526897
TI  - Ultraviolet B exposure and type of lens opacity in ophthalmic patients in Japan.
AB  - Over the course of an individual's lifetime, lens fiber cells proliferate and
      differentiate to form various parts of the lens. The specific pathogenic effects
      of ultraviolet B radiation (UVB), one of the major causes of cataracts, may
      differ depending upon the particular part of the lens. In this study, the
      association of UVB exposure with specific types of lens opacity was investigated
      in relation to lifetime cumulative exposure, and was confirmed by subjects' ages
      at exposure. The severity of lens opacities was assessed by slit lamp examination
      after pupil dilatation. Information on UVB exposure based on place of residence
      and average hours spent outdoors per day was obtained by interview for several
      age ranges of exposure. The effects of UVB exposure on cortical and nuclear
      opacities for both sexes were evaluated using logistic regression analysis. The
      severity of opacities was found to increase with UVB exposure. In particular,
      lifetime cumulative UVB exposure and exposure after the teenage years correlated
      with the presence of nuclear opacities in females. The results indicate that the
      effect of UVB exposure is greater for nuclear than for cortical opacities. This
      is in agreement with the proposed type-specific mechanism for lens opacities
      caused by UVB exposure.

PMID- 12526898
TI  - Iodine-129 in thyroid and urine in Ukraine and Denmark.
AB  - Human thyroids collected from Gomel in Belarus, sheep thyroid from Jutland and
      human urine from Zealand in Denmark were analysed for 129I and 127I
      concentrations. The ratios of 129I/127I in human thyroid in Gomel are 2.65-11.0 x
      10(-9) with an average of 7.21 x 10(-9), which is one order of magnitude higher
      than those from Asia and South America (10(-10)), but significantly lower than
      those observed in west Europe (10(-8)). A weak negative correlation (P < 0.05)
      between 129I/127I ratio in human thyroid and the age of the subjects was observed
      in Gomel. The average ratio of 129I/127I in sheep thyroids from Jutland of
      Denmark is 1.81 x 10(-7), which is two orders of magnitude higher than those in
      south hemisphere, and Asia. It is also significantly higher than those observed
      in other west European countries before 1984 and that in human thyroid in Gomel.
      The high thyroid 129I level in Jutland is attributed to the release of
      reprocessing plants in France and UK. The 129I/127I ratios in human urine in
      Zealand of Denmark are 0.86-2.86 x 10(-8). The possibility of using urine 129I to
      evaluate the thyroid exposure to 129I is investigated.

PMID- 12526899
TI  - The effect of wet film thickness on VOC emissions from a finishing varnish.
AB  - Finishing varnishes, a typical type of oil-based varnishes, are widely used to
      shine metal, wood trim and cabinet surfaces in Hong Kong. The influence of wet
      film thickness on volatile organic compound (VOC) emissions from a finishing
      varnish was studied in an environmental test chamber. The varnish was applied on
      an aluminium foil with three different wet film thickness (35.2, 69.9 and 107.3
      microm). The experimental conditions were 25.0 degrees C, 50.0% relative humidity
      (RH) with an air exchange rate of 0.5 h(-1). The concentrations of the major VOCs
      were monitored for the first 10 h. The air samples were collected by canisters
      and analysed by gas chromatography/mass selective detector (GC/MSD). Six major
      VOCs including toluene, chlorobenzene, ethylbenzene, m,p-xylene, o-xylene and
      1,3,5-trimethylbenzene were identified and quantified. Marked differences were
      observed for three different film thicknesses. VOC concentrations increased
      rapidly during the first few hours and then decreased as the emission rates
      declined. The thicker the wet film, the higher the VOC emissions. A model
      expression included an exponentially decreasing emission rate of varnish film.
      The concentration and time data measured in the chamber were used to determine
      the parameters of empirical emission rate model. The present work confirmed that
      the film thickness of varnish influenced markedly the concentrations and
      emissions of VOCs.

PMID- 12526900
TI  - Nitrate intake from drinking water on Tenerife island (Spain).
AB  - Although meat and vegetable products contain higher concentrations of nitrate,
      drinking water is the fastest and most direct form of nitrate consumption by the
      population. It becomes contaminated with nitrates when sea water infiltrates
      fresh water aquifers and when rain and irrigation water wash through soils that
      have been excessively treated with nitrated fertilizers. Nitrates are of great
      toxicological interest as they are involved in the origin of nitrites and
      nitrosamines and the development of metahaemoglobinaemia in infants. The
      objective of this study was to determine the quantities of NO(3)(-) in the water
      supply of each of the Island's municipalities and in the leading brands of
      bottled waters consumed by the population of Tenerife. This parameter is
      necessary for the determination of Acceptable Daily Intake (A.D.I.) of nitrates
      from drinking water. With one unremarkable exception, the nitrate levels found in
      the water analyzed were optimum for human consumption and amply complied with
      current European Legislation.

PMID- 12526901
TI  - Mercury concentrations in cattle from NW Spain.
AB  - Mercury is a toxic metal that is released into the environment as a result of
      various industrial and agricultural processes. It can be accumulated by domestic
      animals and so contaminate human foodstuffs. To date, there is no information on
      mercury residues in livestock in Spain and the aim of the present study was to
      quantify the concentrations of mercury in cattle in two of the major regions in
      north-west Spain, Galicia (a largely rural region) and Asturias, which is
      characterised by heavy industry and mining. Total mercury concentrations were
      determined in tissue (liver, kidney and muscle) and blood from 284 calves (6-10
      months old) and 56 cows (2-16 years old) from across the whole of the two
      regions. Mercury was usually detected in the kidney (62.4-87.5% of samples) but
      most (79.5-96%) liver, muscle and blood samples did not contain detectable
      residues. Renal mercury concentrations did not differ between male and female
      calves but were significantly greater in female calves than in cows.
      Unexpectedly, kidney mercury concentrations were significantly higher in calves
      from the predominantly rural region of Galicia (geometric mean: 12.2 microg/kg
      w.wt.) than in animals from the industrialised-mining region of Asturias (3.40
      microg/kg w.wt.). Overall, mercury residues in cattle from NW Spain were similar
      to those reported in cattle from non-polluted areas in other countries and do not
      constitute a risk to animal or human health.

PMID- 12526902
TI  - Evaluation of the migration of mutagens/carcinogens from PET bottles into mineral
      water by Tradescantia/micronuclei test, Comet assay on leukocytes and GC/MS.
AB  - This study monitored the release of mutagenic/carcinogenic compounds into mineral
      water (natural and carbonated) from polyethylene terephthalate (PET) bottles,
      using a plant mutagenicity test which reveals micronuclei formation in
      Tradescantia pollen cells (Trad/MCN test), a DNA damage assay (Comet assay) on
      human leukocytes and gas chromatography/mass spectrometry (GC/MS) for the
      characterisation of migrants. The water samples were collected at a bottling
      plant and stored in PET bottles for a period ranging from 1 to 12 months. Every
      month some samples were randomly collected and lyophilised, the residual powders
      were extracted with organic solvents and then analysed by GC/MS and tested for
      DNA damage in human leukocytes, or reconstituted with distilled water to obtain
      concentrates for the exposure of Tradescantia inflorescences. Micronuclei
      increase in pollen was found only in natural mineral water stored for 2 months.
      DNA-damaging activity was found in many of the natural and carbonated water
      samples. Spring water was negative in the plant micronuclei test and the Comet
      assay, whereas distributed spring water showed DNA-damaging effects, suggesting a
      possible introduction of genotoxins through the distribution pipelines. GC/MS
      analysis showed the presence in mineral water of di(2-ethylhexyl)phthalate, a
      nongenotoxic hepatocarcinogenic plasticizer, after 9 months of storage in PET
      bottles.

PMID- 12526903
TI  - Fish tissue quality in the lower Mississippi River and health risks from fish
      consumption.
AB  - Between 1990 and 1994, samples of three shellfish species (i.e. blue crab,
      Callinectes sapidus;crayfish, Procambarus acutis; and river shrimp, Macrobrachium
      ohionii) and 16 fish species and were collected at six sites along the lower
      Mississippi River by the Louisiana Department of Environmental Quality, Office of
      Water Resources in coordination with the US Environmental Protection Agency. The
      fish species included: bigmouth buffalo (Ictiobus cyanellus); blue catfish
      (Ictalurus furcatus); carp (Cyprinus carpio); channel catfish (Ictalurus
      punctatus); cobia (Rachycentron canadum); flathead catfish (Pylodictis olivaris);
      freshwater drum (Aplodinotus grunniens); largemouth bass (Micropterus salmoides);
      long nose gar (Lepisosteus osseus); red drum (Sciaenops ocellatus); red snapper
      (Lutjanus campechanus); smallmouth buffalo (Ictiobus bubalus); spotted gar
      (Lepisosteus oculatus); striped bass (Morone saxatilis); white bass (Morone
      chrysops); and white crappie (Pomoxis annularis). Organic compound and heavy
      metal concentrations were measured in 161 composite fish tissue samples where
      each composite included three to 10 individual fish. Nineteen chemicals, found at
      measurable levels in sample tissues, were used in calculations of lifetime excess
      cancer and non-cancer risks due to fish consumption. We calculated: 574 chemical
      specific cancer risks; 41 total cancer risks; and 697 margins of exposure based
      on a consumption rate of one 8-ounce meal per week (0.032 kg/day), a body weight
      of 70 kg and reported cancer potency factors and reference doses. We identified
      nine species of concern (blue catfish, carp, channel catfish, cobia, crayfish,
      flathead catfish, red drum, spotted gar and striped bass) based on total cancer
      risk greater than 10(-4) or margin of exposure greater than 1, and whether or not
      samples collected in subsequent years resulted in lower risks. The compounds
      primarily responsible for the elevated risks were aldrin, dieldrin, alpha-benzene
      hexachloride, gamma-benzene hexachloride, heptachlor epoxide, arsenic and
      mercury.

PMID- 12526904
TI  - Epidemiological investigation on chronic copper toxicity to children exposed via
      the public drinking water supply.
AB  - Copper in drinking water has been associated with Non-Indian Childhood Cirrhosis
      (NICC), a form of early childhood liver cirrhosis. This epidemiological study
      examines the exposition of infants to increased copper concentrations through
      drinking water from public water supplies in Berlin, Germany, and if this dietary
      copper intake can cause liver damage in early childhood. In total, water samples
      from 2944 households with infants were tested for copper. Mean copper
      concentrations in the two different types of collected composite samples were
      0.44 and 0.56 mg/l, respectively. Families having a copper concentration at or
      above 0.8 mg/l in one or both of the composite samples (29.9% of all sampled
      households) and a defined minimum ingestion of tap water of their infant were
      recommended to undergo a paediatric examination. Nearly every of the 541
      recommended infants were examined by a local paediatrician and of these 183
      received a blood serum analysis, too. None of the infants had clear signs of a
      liver disease although a few serum parameters lay outside the accompanying
      reference range and abdominal ultrasound imaging gave slightly unusual results in
      five cases. Additionally, no signs of a negative health effect could be found in
      the statistical analysis of the serum parameters GOT, GPT, GGT, total bilirubin,
      serum copper, or ceruloplasmin in relation to estimated daily and total copper
      intakes of the infants from tap water. No dose relation of serum parameters and
      estimated copper intakes could be established. From the results of the study, no
      confirmed indication of a liver malfunction in infants whose food had been
      prepared using tap water with an elevated copper concentration could be found
      and, therefore, no indication of a hazard due to copper pipes connected to public
      water supplies could be detected.

PMID- 12526905
TI  - Partitioning of persistent organic pollutants in grey seal (Halichoerus grypus)
      mother-pup pairs.
AB  - Phocid seals have lipid rich milk, which is known to serve as a transfer medium
      through which persistent organic pollutants (POPs) move from mother to offspring
      during lactation. However, knowledge on this generational transfer of different
      POPs and the partitioning of these compounds in maternal and offspring tissues
      over the course of the lactation are limited. In this study we examined the
      qualitative and quantitative partitioning of a range of chlorinated POPs in
      maternal blubber, blood and milk as well as in pup blubber, collected early in
      the lactation period and late in the lactation period. In the lactating female,
      the high-chlorinated and hydrophobic compounds were passed less efficiently into
      the milk than the low-chlorinated compounds and more water-soluble compounds.
      Significantly, lower maternal blood concentrations than in maternal blubber
      biopsies suggest a stratification of POP concentrations in the blubber column of
      lactating female and lower concentrations in the metabolic active inner layers.
      Over the course of lactation, there was a significant increase in maternal blood
      and milk concentrations of POPs as opposed to no change in maternal blubber
      biopsy concentrations. This was most apparent for the hydrophobic and high
      chlorinated compounds. The most likely explanation for this is that the metabolic
      active inner blubber layer, from which the milk lipids are derived from, is in
      steady state with the circulatory system, while the outer layers are more static
      and only slowly respond to changes in concentrations elsewhere in the body. The
      concentrations of the high-chlorinated and hydrophobic compounds were
      substantially lower in pup blubber than in maternal blubber. This probably
      relates the combined effect of these compounds stratification in maternal blubber
      and their slow transfer into the milk. The present study shows that the more
      hydrophobic and high-chlorinated compounds come to steady state less quickly in
      the different tissues than the more water-soluble and low-chlorinated compounds
      in the lactating female and her offspring. This has implications for which
      matrices to choose when sampling for assessing the toxicological risk of POPs in
      seals.

PMID- 12526906
TI  - Low trihalomethane formation in Korean drinking water.
AB  - Organics in water have the potential to generate harmful disinfection by-products
      (DBPs) such as trihalomethanes (THMs) during the chlorination process. To clarify
      the regulatory implications of Korean THMs levels which appear to be
      significantly lower than those in the US where the Stage 1 and 2 D/DBPs rule has
      been promulgated, the characteristics of THMs formation were investigated on five
      major river waters in Korea. Water samples were taken from 12 water treatment
      plants on five major rivers that serve as drinking water sources for more than
      90% of the Korean population. Trihalomethane formation potential (THMFP), total
      organic halide formation potential (TOXFP) and ultraviolet absorbance at 254 nm
      (UV(254)) were determined and compared with those from US data. A survey of
      existing data [J Korean Soc Water Qual; 16(4) 2000b 431-443] provided evidence
      that THMs levels in treated drinking water in Korea were one-third of those
      reported in the US. The lower THMs levels were mainly attributable to the
      differences in the level and THMFP of dissolved organic carbon (DOC). The DOC
      levels and the THMFP normalized to DOC were approximately 60% of those in the US.
      Results which combined could quantitatively account for the lower THMs levels
      (i.e. 0.6 x 0.6 approximately 1/3) in Korea. The observed Korean THMs levels were
      over-predicted by the THMs model () developed in the US. The level of THMFP was
      found to be similar if normalized for aromaticity as measured by UV(254). These
      findings suggest that: (i) the case for more stringent THMs control is not likely
      to be a high priority among issues of drinking water quality in Korea; and (ii)
      significant variation of THMFP level may exist over different geographic regions;
      hence (iii) independent THMs models should be developed to make accurate
      predictions for different regions.

PMID- 12526907
TI  - Impact on global metal flows arising from the use of portable rechargeable
      batteries.
AB  - The use of portable rechargeable battery cells and their effects on global metal
      flows were assessed or the following three cases: (1) the base case, which
      reflects the situation in 1999 of the global production of batteries; (2) the
      global production of portable nickel-cadmium batteries in 1999, assumed to be
      replaced by other battery types; and (3) assessment of the projected battery
      market in 2009. The study included the following battery technologies: nickel
      cadmium (NiCd); nickel-metal hydride (NiMH) (AB(5), AB(2)); and lithium-based
      batteries (Li-ion: Co, Ni, Mn; Li-polymer: V). Based on the lithospheric
      extraction indicator (LEI), which is the ratio of anthropogenic to natural metal
      flows, and the significance of battery production related to global metal mining,
      the potential environmental impact of metals used in different battery types was
      evaluated. The LEIs and average metal demand for the battery market in 1999,
      expressed as a percentage of global mining output in 1999, were estimated to be
      as follows: Ni 5.6 (2.0%); Cd 4.4 (37%); Li 0.65 (3.8%); V 0.33 (6.5%); Co 0.18
      (15%); Nd 0.18 (8.4%); La 0.10 (9.5%); Ce 0.083 (4.4%); and Pr 0.073 (9.4%). The
      use of Ni and Cd is of the greatest environmental interest, due to their high
      LEIs. In the case of complete replacement of portable NiCd batteries by NiMH or
      Li-based batteries, the LEI for Ni (5.6) would change by -0.1-0.5% and the LEI
      for Cd would decrease from 4.4 to 3.0 (-31%). Meanwhile, the mobilization of
      metals considered less hazardous than Cd (LEI 0 < 5) would increase less than 7%.
      Based on this assessment, the replacement of NiCd batteries would result in
      decreased environmental impact. To decrease the impact on global metal flows
      arising from the use of portable batteries the following points should be
      considered: (1) development of battery technologies should aim at high energy
      density and long service life; (2) metals with high natural occurrence should be
      used; and (3) metals from disused batteries should be recovered and regulations
      implemented to decrease the need for mining of virgin metals. The method used
      enables an assessment early in the cause-effect chain, when few data about toxic
      effects are available. It can also be used to assess whether environmental
      problems are shifted from one to another.

PMID- 12526908
TI  - Effect of chlorine content in feeding wastes of incineration on the emission of
      polychlorinated dibenzo-p-dioxins/dibenzofurans.
AB  - This study attempts to clarify the effects of chlorine content in waste on the
      formation mechanisms of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) in full scale incinerators by proposing and using the principal
      component analysis (PCA) to compare the congener profiles of PCDD/Fs in the stack
      flue gases of 17 emission sources, including incinerators and vehicles. Four
      incinerators, among these 17 emission sources, were sampled and analyzed in this
      study, and the data for the other 13 emission sources were selected from previous
      studies. These 17 emission sources can be classified into four categories,
      including medical waste incinerators (MWIs, H1-H5), municipal solid waste
      incinerators (MSWIs, M1-M8), vehicle fuel combustion (unleaded gas-fueled
      vehicles, UGFV; diesel-fueled vehicles, DFV, n = 2) and polyvinylchloride (PVC)
      facility vent combustors (PVC1 and PVC2, n = 2). PCA was conducted for these
      emission sources with the fractions of 17 2,3,7,8-congeners in the stack flue
      gases as variables to clarify the effect of chlorine content in feeding wastes on
      the emission of PCDD/Fs. From the results of PCA, we extrapolated that the
      threshold value of the chlorine content was at 0.8-1.1%, and the formation
      mechanisms of PCDD/Fs are influenced first by whether the chlorine content in the
      feeding waste is over or below the threshold value then by other factors, which
      furnaces or APCDs represent. When the chlorine level in the waste is below the
      threshold value at 0.8-1.1%, the formation of PCDDs dominates, probably because
      the chlorine is used to chlorinate the non-substituted phenol to produce
      chlorophenols, which are important precursors for PCDDs. rather than chlorinate
      the dibenzofuran. While the chlorine level in the waste exceeds this threshold
      (0.8-1.1%), the rates of formation of PCDFs increase faster than those of PCDDs,
      probably because the chlorine content in the waste contributes to the
      deterioration of combustion conditions, and many products of incomplete
      combustion (PICs) like PAHs, will grow to a substantial level. When PCDD/Fs are
      formed from PAHs, the formation rates of PCDFs are higher than those of PCDDs.

PMID- 12526909
TI  - Fate of natural estrogen conjugates in municipal sewage transport and treatment
      facilities.
AB  - The aim of this study was to investigate the fate of the conjugated forms of the
      three most common natural estrogens in the municipal aqueous environment. Levels
      of conjugated and free estrogens in (1) female urine; (2) a septic tank
      collecting domestic wastewater; (3) influents and effluents of six activated
      sludge sewage treatment plants (STPs) were measured. The analytical method was
      based on solid-phase extraction by using a Carbograph 4 cartridge and Liquid
      Chromatography-tandem Mass Spectrometry. On average, a group of 73 women selected
      to represent a typical cross section of the female inhabitants of a Roman
      condominium, excreted 106, 14 and 32 microg/day of conjugated estriol (E(3)),
      estradiol (E(2)) and estrone (E(1)), respectively. Apart from some E(3) in
      pregnancy urine, free estrogens were never detected in urine samples. Estrogen
      sulfates represented 21% of the total conjugated estrogens. This situation
      changed markedly in the condominium collecting tank. Here, significant amounts of
      free estrogens were observed and the estrogen sulfate to estrogen glucuronated
      ratio rose to 55/45. A laboratory biodegradation test confirmed that glucuronated
      estrogens are readily deconjugated in unmodified domestic wastewater, presumably
      due to the large amounts of the beta-glucuronidase enzyme produced by fecal
      bacteria (Escherichia coli). Deconjugation continued in sewer transit. At the STP
      entrance, free estrogens and sulfated estrogens were the dominant species. The
      sewage treatment completely removed residues of estrogen glucuronates and with
      good efficiency (84-97%) the other analytes, but not E(1) (61%) and estrone-3
      sulfate (E(1)-3S) (64%). Considering that (1) E(1) has half the estrogenic
      potency of E(2), (2) the amount of the former species discharged from STPs into
      the receiving water was more than ten times larger than the latter one and (3) a
      certain fraction of E(1)-3S could be converted to E(1) in the aquatic
      environment, E(1) appears to be the most important natural endocrine disrupter.

PMID- 12526910
TI  - Carbonyl levels in indoor and outdoor air in Mexico City and Xalapa, Mexico.
AB  - Carbonyl compounds in air were measured at two houses, three museums, and two
      offices. All sites lacked air-conditioning systems. Although indoor and outdoor
      air was measured simultaneously at each site, the sites themselves were sampled
      in different dates. Mean concentrations were higher in indoor air. Outdoor means
      concentrations of acetone were the highest in all sites, ranging from 12 to 60
      microg m(-3). In general, formaldehyde and acetaldehyde had similar mean
      concentrations, ranging from 4 to 32 and 6 to 28 microg m(-3), respectively.
      Formaldehyde and acetone mean indoor concentrations were the highest, ranging
      from 11 to 97 and 17 to 89 microg m(-3), respectively, followed by acetaldehyde
      with 5 to 47 microg m(-3). Formaldehyde and acetaldehyde had the highest mean
      concentration in the offices where there were smokers. Propionaldehyde and
      butyraldehyde concentrations did not show definite differences between indoor and
      outdoor air. In general, the highest outdoor and indoor hourly concentrations
      were observed from 10:00 to 15:00 h. Mean indoor/outdoor ratios of carbonyls
      exceeded 1. Formaldehyde and acetaldehyde risks were higher in smoking
      environments.

PMID- 12526911
TI  - Emissions and environmental implications of mercury from artisanal gold mining in
      North Sulawesi, Indonesia.
AB  - In artisanal gold mining practiced in North Sulawesi Island, Indonesia, gold is
      separated from ore by the use of mercury, which forms an amalgam with gold. All
      related processes are undertaken with a low level of technical knowledge and
      skills, no regulation, and with disregard for the safety of human and environment
      health. The situation is generating serious potential health and environmental
      risks in the area. As part of an ongoing monitoring program, total mercury
      concentrations were examined in water, bottom sediment and fish samples from
      three main rivers in Talawaan Watershed, which receives drainage from gold mining
      practices. Monitoring began in May-June 2000, almost 2 years after artisanal gold
      mining had begun. At that time, the mercury concentration in the sediment was
      generally low, except in places close to the gold processing plants. In the
      present study, a more systematic sampling and analysis was conducted in May-June
      2001. Bottom surface sediments, water, and fish samples were collected at 12
      sites along the three main rivers in the watershed. In addition, one site outside
      the watershed was sampled to serve as a control. Sample collections were
      conducted in three phases in duplicate, with two-week intervals between each
      phase. The mercury concentration observed in this study indicated that an
      increase took place along the three main rivers in the watershed. Solutions to
      this problem must be formulated as soon as possible in order to avoid a major
      health, economic, and ecological disaster arising from the continuing discharge
      of Hg. The present study proposes that mercury dispersion occur downstream of the
      mining.

PMID- 12526912
TI  - Photodegradation of roxarsone in poultry litter leachates.
AB  - Arsenic compounds have been used extensively in agriculture in the US for
      applications ranging from cotton herbicides to animal feed supplements. Roxarsone
      (3-nitro-4-hydroxyphenylarsonic acid), in particular, is used widely in poultry
      production to control coccidial intestinal parasites. It is excreted unchanged in
      the manure and introduced into the environment when litter is applied to farmland
      as fertilizer. Although the toxicity of roxarsone is less than that of inorganic
      arsenic, roxarsone can degrade, biotically and abiotically, to produce more toxic
      inorganic forms of arsenic, such as arsenite and arsenate. Experiments were
      conducted on aqueous litter leachates to test the stability of roxarsone under
      different conditions. Laboratory experiments have shown that arsenite can be
      cleaved photolytically from the roxarsone moiety at pH 4-8 and that the
      degradation rate increases with increasing pH. Furthermore, the rate of
      photodegradation increases with nitrate and natural organic matter concentration,
      reactants that are commonly found in poultry-litter-water leachates. Additional
      photochemical reactions rapidly oxidize the cleaved arsenite to arsenate. The
      formation of arsenate is not entirely undesirable, because it is less mobile in
      soil systems and less toxic than arsenite. A possible mechanism for the
      degradation of roxarsone in poultry litter leachates is proposed. The results
      suggest that poultry litter storage and field application practices could affect
      the degradation of roxarsone and subsequent mobilization of inorganic arsenic
      species.

PMID- 12526913
TI  - Mineralogical study of salt crusts formed on historic building stones.
AB  - A historic building stone, Baumberger sandstone, was exposed to gaseous SO(2)
      under dry and wet surface conditions in an atmospheric test chamber. The extent
      of salt formation resulting from the exposure to pollutant gases as well as the
      variations in mineralogical composition were studied based on petrological thin
      sections. Results reveal that the salts are formed only over the surface of the
      sample. The thickness of the formed salt crusts is determined. Calcite
      dissolution as well as porosity decreases are due to gypsum formation.

PMID- 12526914
TI  - In vitro formation of pyromorphite via reaction of Pb sources with soft-drink
      phosphoric acid.
AB  - Pyromorphite (Pb(5)(PO(4))(3)Cl) is a Pb mineral whose rapid kinetic formation
      and thermodynamic stability (Geochim. Cosmochim. Acta 37 (1973) 367, Geochim.
      Cosmochim. Acta 38 (1974) 887) has gained much attention in recent years as a
      mechanism to diminish Pb toxicity. Our research examined the in vitro formation
      of pyromorphite (K(sp) = 10(-25)) to significantly reduce Pb bioavailability via
      the reaction of PbCl(2) and Pb paint with cola soft drinks (regular, caffeine
      free, and diet) that contain phosphoric acid. X-ray diffraction spectroscopy was
      employed to identify and quantify the crystal phases. The experiments consisted
      of a two-phase experimental design to simulate stomach and gastrointestinal (GI)
      conditions comprised of an initial reaction system (stomach) at pH 2.0 for 1 h at
      37 degrees C and second-phase conditions (GI tract) at pH 7.0 for 5 h at 37
      degrees C. The results showed that available Pb in solution was quickly
      transformed to pyromorphite by a precipitation mechanism. The PbCl(2) experiments
      observed over 90% Pb removal from solution within 30 s and nearly all (> 93-100%)
      of the Pb was converted to pyromorphite within 6 h. Similar results were observed
      in the Pb-paint system in which all of the available Pb initially available in
      solution was stabilized as pyromorphite within a short reaction period. While
      approximately 69% of the total Pb in the paint was converted to pyromorphite,
      there were minimal amounts of Pb in solution. It appeared that the dissolution
      mechanism allowing Pb in the paint to be released into the cola solution was
      repressed and was attributed to precipitation of pyromorphite on the surfaces of
      Pb-paint particles that inhibited further Pb release. The results of this
      research suggest that the in vivo formation of pyromorphite in children that
      ingest Pb-contaminated material (soil, dust, paint) with a phosphate source, such
      as a cola soft drink, may significantly reduce Pb bioavailability and allow
      passage of the pyromorphite material through the GI tract with minimal Pb
      absorption into the body.

PMID- 12526915
TI  - Manganese micro-nodules on ancient brick walls.
AB  - Romans, Jews, Arabs and Christians built the ancient city of Toledo (Spain) with
      bricks as the main construction material. Manganese micro-nodules (circa 2 microm
      in diameter) have grown under the external bio-film surface of the bricks. Recent
      anthropogenic activities such as industrial emissions, foundries, or traffic and
      housing pollution have further altered these old bricks. The energy-dispersive X
      ray microanalyses (XPS) of micro-nodules show Al, Si, Ca, K, Fe and Mn, with some
      carbon species. Manganese atoms are present only as Mn(4+) and iron as Fe(3+)
      (FeOOH-Fe(2)O(3) mixtures). The large concentration of alga biomass of the River
      Tagus and the Torcon and Guajaraz reservoirs suggest manganese micro-nodules are
      formed either from water solutions rich in anthropogenic MnO(4)K in a reduction
      environment (from Mn(7+) to Mn(4+)) or by oxidation mechanisms from dissolved
      Mn(2+) (from Mn(2+) to Mn(4+)) linked to algae biofilm onto the ancient brick
      surfaces. Ancient wall surfaces were also studied by scanning electron microscopy
      (SEM-EDS) and X-ray diffraction (XRD). Chemical and biological analyses of the
      waters around Toledo are also analysed for possible sources of manganese.
      Manganese micro-nodules on ancient brick walls are good indicators of manganese
      pollution.

PMID- 12526916
TI  - The myelodysplastic syndrome(s): a perspective and review highlighting current
      controversies.
AB  - The myelodysplastic syndrome (MDS) includes a diverse group of clonal and
      potentially malignant bone marrow disorders characterized by ineffective and
      inadequate hematopoiesis. The presumed source of MDS is a genetically injured
      early marrow progenitor cell or pluripotential hematopoietic stem cell. The blood
      dyscrasias that fall under the broad diagnostic rubric of MDS appear to be quite
      heterogeneous, which has made it very difficult to construct a coherent,
      universally applicable MDS classification scheme. A recent re-classification
      proposal sponsored by the World Health Organization (WHO) has engendered
      considerable controversy. Although the precise incidence of MDS is uncertain, it
      has become clear that MDS is at least as common as acute myelogenous leukemia
      (AML). There is considerable overlap between these two conditions, and the former
      often segues into the latter; indeed, the distinction between AML and MDS can be
      murky, and some have argued that the current definitions are arbitrary. Despite
      the discovery of several tantalizing pathophysiological clues, the basic biology
      of MDS is incompletely understood. Treatment at present is generally frustrating
      and ineffective, and except for the small subset of patients who exhibit mild
      marrow dysfunction and low-risk cytogenetic lesions, the overall prognosis
      remains rather grim. In this narrative review, we highlight recent developments
      and controversies within the context of current knowledge about this mysterious
      and fascinating cluster of bone marrow failure states.

PMID- 12526917
TI  - Thrombopoietin expression and plasma concentrations in chronic myeloproliferative
      disorders.

PMID- 12526918
TI  - Expression of sorcin predicts poor outcome in acute myeloid leukemia.
AB  - Using a cDNA microarray 12 differentially expressed genes were identified in a
      multidrug resistant (MDR) cell line K562/A02. The differential expression of
      sorcin, which was one of the 12 genes, has been confirmed by Northern blot. To
      determine the clinical role of sorcin, we have measured its expression in
      leukemic blast cells of 65 acute myeloid leukemia (AML) patients by reverse
      transcriptase polymerase chain reaction (RT-PCR). Sorcin overexpression in AML
      patients was associated with poor clinical outcomes, the complete remission (CR)
      rate in sorcin- cases was significantly higher than that of sorcin+ cases
      (P<0.001). Furthermore, sorcin expression in AML patients was positively
      correlated with mdr1 expression (r=0.841, P<0.001). Combination of sorcin and
      mdr1 was related to clinical outcome too, cases with sorcin-/mdr1- had best
      response to induction chemotherapy. Our results indicated that sorcin might be
      one of the factors that contributes to drug resistance of AML patients.

PMID- 12526919
TI  - Mevastatin can increase toxicity in primary AMLs exposed to standard therapeutic
      agents, but statin efficacy is not simply associated with ras hotspot mutations
      or overexpression.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a rate-limiting
      enzyme in the mevalonate biochemical pathway and HMG-CoA reductase inhibitors
      (statins) show toxicity for certain tumors, including acute myeloid leukemia
      (AML). This toxicity has been attributed to statin inhibition of Ras
      isoprenylation in tumors like AML where oncogenic ras mutations and/or
      overexpression are common. We show that mevastatin kills certain AML cell lines
      and is more toxic to a majority of primary AML cell samples than to myeloid cells
      in bone marrow (BM) samples from normal donors, and that mevastatin can produce
      more than additive kill with standard chemotherapeutics. Mevastatin reduces Ras
      membrane localization, but statin sensitivity in primary AML cells is not
      consistently associated with ras mutations nor with Ras overexpression,
      suggesting that another mevalonate pathway by-product(s) is the statin target in
      at least some AMLs.

PMID- 12526920
TI  - Metabolism of chylomicron-like emulsions in patients with Hodgkin's and with non
      Hodgkin's lymphoma.
AB  - BACKGROUND: Chylomicrons carry in the bloodstream dietary fats absorbed the
      intestine for storage in the body tissues such as adipose and muscle. The two
      step chylomicron metabolism consists in lipolysis by lipoprotein lipase on vessel
      walls and hepatic uptake of triglyceride-depleted remnants. Chylomicron
      metabolism is understudied in cancer, despite its direct involvement in the
      patient nutritional status. We investigated this metabolism in Hodgkin and non
      Hodgkin lymphoma patients, using the method of triglyceride-rich emulsions that
      mimic chylomicrons. PATIENTS AND METHODS: The chylomicron-like emulsion, labeled
      with [9,10-3H]glycerol-trioleate and [1-14C] cholesteryl-oleate was intravenously
      injected into 11 Hodgkin's, 19 non-Hodgkin's patients and 12 healthy subjects.
      Triglyceride kinetics evaluate lipolysis whereas cholesteryl ester kinetics
      evaluate remnant removal. RESULTS: Plasma total, LDL, HDL cholesterol, apo B, apo
      A1 and Lp(a) values were similar between the three groups, but VLDL cholesterol
      and triglycerides were higher in the lymphoma groups. The fractional catabolic
      rate (FCR, in min(-1)) of the emulsion triglycerides was roughly three-fold
      smaller in non-Hodgkin's (0.043+/-0.007, mean+/-S.E.M., P<0.001) and Hodgkin's
      (0.045+/-0.009, P<0.0001) lymphoma patients compared with the control values
      (0.151+/-0.032). FCR of the emulsion cholesteryl esters, was four-fold smaller in
      non-Hodgkin's (0.016+/-0.002, P<0.0001), and three-fold in Hodgkin's lymphoma
      patients (0.024+/-0.006, P<0.001) compared with the control group (0.069+/
      0.013). The lipolysis index, calculated from the decay curves of both isotopes
      was also markedly smaller in both groups of lymphoma patients compared with the
      controls. CONCLUSIONS: In both lymphoma groups, marked alterations in chylomicron
      lipolysis and remnant removal occurs.

PMID- 12526921
TI  - TEL-AML1 fusion precedes differentiation to pre-B cells in childhood acute
      lymphoblastic leukemia.
AB  - The TEL-AML1 gene fusion results from a karyotypically cryptic t(12;21)
      translocation, the most common genetic abnormality in pediatric acute
      lymphoblastic leukemia (ALL). The presence of the TEL-AML1 fusion in utero, its
      protracted latency to overt leukemia, and secondary loss of the untranslocated
      TEL suggest it is an initiating event. Sequences of the TEL-AML1 genomic
      breakpoint and the immunoglobulin heavy chain (IgH) and/or T-cell receptor (TCR)
      gene rearrangements were characterized in four pediatric pre-B ALL patients.
      Analysis of these markers in relapsed patients revealed that immunophenotypically
      and cytogenetically distinct, and clonally unrelated antigen receptor leukemic
      cell populations harbored the same initiating TEL-AML1 molecular abnormality.
      Furthermore, TEL-AML1-positive cells persisted during remission even in the
      absence of detectable clone-specific IgH and TCR markers. We demonstrate that the
      TEL-AML1 translocation can occur in vivo during B-cell development before
      rearrangement of the IgH and TCR genes. We propose, in some cases, that the TEL
      AML1 translocation occurs in a stem or B progenitor cell, and that recurrent TEL
      AML1-positive pre-B ALL represents a de novo-transformed population that retains
      the same diagnostic initiating event.

PMID- 12526922
TI  - Megakaryoblastic leukemia cell line MOLM-16 derived from minimally differentiated
      acute leukemia with myeloid/NK precursor phenotype.
AB  - The megakaryoblastic leukemia cell line MOLM-16 was established at relapse from
      the peripheral blood of a 77-year-old Japanese woman with minimally
      differentiated acute myeloid leukemia (AML-M0). Immunophenotyping of the fresh
      leukemic cells revealed a myeloid/NK precursor phenotype being positive for CD7,
      CD13, CD33, CD34, and CD56. In addition, megakaryocyte-associated antigens CD41
      and CD61 were found to be positive. The established cell line designated MOLM-16
      was proliferatively responsive to the treatment with various cytokines including
      EPO, GM-CSF, IL-3, PIXY-321, and TPO. MOLM-16 revealed characteristics of the
      megakaryocytic lineage in terms of immunophenotyping being positive for CD9,
      CD31, CD36, CD41, CD61, CD62P, CD63, CD110, CD151, thrombospondin, von Willebrand
      factor (vWf), and fibrinogen. Electron microscopic analysis showed positivity for
      ultrastructural platelet peroxidase in the nuclear envelope. The karyotype
      analysis of MOLM-16 revealed various numerical and structural abnormalities
      including t(6;8)(q21;q24.3), t(9;18)(q13;q21) and marker chromosomes. The
      extensive immunological, cytogenetic and functional characterization of MOLM-16
      suggests that this cell line may represent a scientifically significant in vitro
      model which could facilitate the evaluation of megakaryocytic differentiation.

PMID- 12526923
TI  - Fc epsilon RI and CD22 mRNA are expressed in early B-lineage and myeloid leukemia
      cell lines.
AB  - CD22, one of the important markers for diagnosing B-lineage acute leukemia, was
      expressed in mature basophil granulocytes. We then investigated the expression of
      CD22 and other B cell- and basophil-related molecules in 25 human acute leukemia
      cell lines to find the phenotype of the virtual common progenitor of B and
      myeloid lineage. Surface and cytoplasmic expressions of antigens were analyzed
      using a flow cytometer and an essential antibody panel used for diagnosing acute
      leukemia as well as cytokine receptors and basophil-related enzymes. Messenger
      RNA expression of Fc epsilon R1 and CD22 was also analyzed. Peroxidase-positive
      and -negative myeloid leukemias showed eosinophil- and basophil-type expression
      of enzymes, respectively. Early myeloid and B-lineage cells expressed basically
      similar combinations of cytokine receptors and various combinations of mRNA
      listed above, while T-lineage cells did not. The virtual common progenitor of B
      and myeloid lineage cells may be defined as immature cells simultaneously
      expressing B and basophil phenotypes.

PMID- 12526925
TI  - CMV-induced immune thrombocytopenia and excessive hematogones mimicking an acute
      B-precursor lymphoblastic leukemia.
AB  - Hematogones (B-lymphocyte progenitor-precursor cells) are normal bone marrow
      constituents which are morphologically distinct lymphoid cells with homogeneous,
      condensed uniform nuclear chromatin and scant cytoplasm. Hematogones can be
      observed in large numbers in the bone marrow of children with a variety of
      hematologic and nonhematologic disorders.We present here a 3.5-month-old boy with
      cytomegalovirus (CMV)-induced immune thrombocytopenia and excessive hematogones
      in the bone marrow mimicking an acute B-precursor lymphoblastic leukemia. To our
      knowledge this is the first case of acute CMV infection-induced immune
      thrombocytopenia with hematogones.

PMID- 12526924
TI  - Different effects of metabolic inhibitors and cyclosporin A on daunorubicin
      transport in leukemia cells from patients with AML.
AB  - The objective of this study was to determine the role of transport proteins in
      daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients
      with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated
      with 1 microM Dnr with/without addition of 3 microM cyclosporin A (CyA) or
      metabolic inhibitors (MI). Cellular Dnr concentration in leukemia blast cells was
      measured with flow cytometry. After washing and reincubation of the cells in drug
      free medium, Dnr efflux was followed with/without addition of CyA or MI. Levels
      of mRNA expression for mdr1, multidrug resistance associated protein (mrp) and
      lung resistance protein (lrp) were determined with reverse transcriptase
      polymerase chain reaction (RT-PCR). MI enhanced cellular Dnr accumulation to a
      higher extent than CyA whereas CyA reduced Dnr efflux more efficiently than MI
      (P<0.001). There was a significant difference in Dnr accumulation between samples
      with low and high mdr1 mRNA levels but only in the presence of MI or CyA. Our
      results imply that other factors than P-glycoprotein (Pgp) are of major
      importance for in vitro Dnr accumulation in AML blasts and that the role of Pgp
      as a drug efflux pump is not conclusive.

PMID- 12526926
TI  - Repeat sphincterotomy: does its safety depend on the interval from the initial
      procedure?

PMID- 12526927
TI  - Surveillance cultures to monitor quality of gastrointestinal endoscope
      reprocessing.

PMID- 12526928
TI  - Infliximab treatment of Crohn's disease in children: it's time to not go
      retro(spective).

PMID- 12526929
TI  - Cytokine gene polymorphisms in chronic hepatitis B: a step up the immunology
      ladder.

PMID- 12526930
TI  - A systematic review of neuroimaging data during visceral stimulation.
AB  - OBJECTIVE: The application of functional imaging to study visceral sensation has
      generated considerable interest regarding insight into the function of the brain
      gut axis, but also some contradictory and confusing results that require
      appraisal. METHODS: Published studies of visceral sensation were grouped
      according to stimulus region and study population. The results of each study were
      tabulated and the center of reported activations plotted onto the lateral and
      medial surface of a representative brain. RESULTS: Esophageal distension
      predominantly activated primary sensory and motor cortices and the midsection of
      the medial surface. Lower GI distension predominantly activated bilateral
      prefrontal and orbitofrontal cortices and more anterior and ventral regions of
      the medial surface. CONCLUSIONS: Activation sites are reasonably well clustered
      within stimulus modality, implying consistent brain response to visceral
      sensation. The differences in reported activation during esophageal and lower GI
      sensation imply altered motor, autonomic, and affect response during distension
      at opposite ends of the GI tract that may be explored in future studies.

PMID- 12526931
TI  - Gastroenterologist specialist care and care provided by generalists--an
      evaluation of effectiveness and efficiency.
AB  - OBJECTIVE: In this era of cost containment, gastroenterologists must demonstrate
      that they provide effective and efficient care. The aim of this study was to
      evaluate the process and outcomes of care provided by gastroenterologists and
      generalist physicians (internists, family physicians, general surgeons) for GI
      conditions. METHODS: We conducted a systematic literature review using a MEDLINE
      search of English language articles (January 1980 to September 1998). A total of
      2157 articles were identified; 10 met inclusion criteria for systematic review.
      In addition, there were nine articles that described the results of physician
      surveys, and examined the process of care among gastroenterologists and
      generalist physicians. RESULTS: Care provided by gastroenterologists for GI
      bleeding and diverticulitis resulted in significantly shorter length of hospital
      stay. Gastroenterologists diagnosed celiac disease more accurately than
      generalists, and more adequately diagnosed colorectal cancer and prescribed
      antimicrobials for peptic ulcer disease. There was no difference between
      gastroenterologists and generalists in terms of colonoscopy procedure time, and
      family physicians detected a greater number of cancers. Furthermore, there was no
      difference in the outcomes of gastroesophageal reflux disease therapy in patients
      seen by gastroenterologists, versus those educated by nurses. The survey articles
      suggested that gastroenterologists were more likely to test and treat for
      Helicobacter pylori in patients with peptic ulcer disease, and were more likely
      recommended for medical versus surgical therapy. Gastroenterologists had a lower
      threshold for ordering ERCP before cholecystectomy than surgeons, but had similar
      responses regarding indications for surgery in inflammatory bowel disease.
      Finally, primary care physicians were less likely to associate symptoms of
      profuse watery diarrhea with cryptosporidium infection compared with
      gastroenterologists and infectious disease specialists. CONCLUSIONS: We reached
      the following conclusions: 1) The results suggest that gastroenterologists
      deliver effective and efficient care for GI bleeding and diverticulitis and
      provide more effective diagnosis in certain disorders. 2) Studies are limited by
      retrospective design, small sample size, and lack of control groups. 3) To fully
      evaluate care by gastroenterologists, prospective comparisons with greater
      attention to methodology are needed.

PMID- 12526932
TI  - Effect of laparoscopic partial fundoplication on reflux mechanisms.
AB  - OBJECTIVES: Transient lower esophageal sphincter relaxations (TLESRs) are the
      main mechanism causing gastroesophageal reflux. Since 1994 we have performed
      laparoscopic partial instead of complete fundoplication as standard surgical
      treatment for therapy resistant reflux disease to minimize postoperative
      dysphagia. To better understand the management of gastroesophageal reflux, we
      conducted a prospective study of the effects of laparoscopic partial
      fundoplication on TLESRs and other reflux mechanisms. METHODS: From 1994 to 1999,
      65 patients underwent laparoscopic partial fundoplication (180-200 degrees) and
      28 of these patients (16 female, 12 male, mean age 43 +/- 2 yr [range, 26-66 yr])
      agreed to participate in this prospective study on reflux mechanisms. Before and
      6 months after surgery, all patients were evaluated by simultaneous recording of
      pH and lower esophageal sphincter characteristics, using sleeve manometry.
      RESULTS: After partial fundoplication basal LES pressure increased significantly
      (p < 0.05), from 14.3 +/- 1.2 mm Hg to 17.8 +/- 1 mm Hg. Partial fundoplication
      significantly (p < 0.05) decreased the number of TLESRs, from 3.4 +/- 0.8 to 1.6
      +/- 0.3 per hour in the fasting period, and from 4.7 +/- 0.5 to 1.9 +/- 0.3 per
      hour postprandially. The percentage of TLESRs associated with reflux also
      decreased significantly (p < 0.05), from 45 +/- 7% to 27 +/- 6% after operation.
      The number of reflux episodes decreased significantly (p < 0.05), from 4.1 +/-
      0.7 to 1.3 +/- 0.3 per hour postoperatively. The majority of these episodes were
      associated with TLESRs: 57% and 46%, pre- and postoperatively, respectively.
      CONCLUSIONS: Laparoscopic partial fundoplication significantly increased fasting
      and postprandial LES pressure and significantly decreased TLESR frequency. This
      resulted in a significant reduction in esophageal acid exposure, with
      preservation of postprandial LES characteristics.

PMID- 12526933
TI  - Failure of esophageal peristalsis in older patients: association with esophageal
      acid exposure.
AB  - OBJECTIVES: Gastroesophageal reflux disease (GERD) is common in all ages, but its
      prevalence appears to increase with age. Older patients often need aggressive
      medical therapy and are frequently being considered for antireflux surgery. We
      sought to evaluate the physiological defect (lower esophageal sphincter [LES]
      pressures, esophageal motility, and acid exposure) in a group of GERD patients
      >or= 65 yr old in comparison with a younger population (<or=40 yr). We
      hypothesized that age has an adverse impact on esophageal motility and reflux
      parameters. METHODS: Consecutive patients who completed esophageal manometry and
      ambulatory pH testing in our laboratory were evaluated for the study. The study
      group consisted of those >or=65 yr old and the control group of those <or=40 yr
      old. Each group was then divided according to their percent esophageal acid (pH <
      4.0) exposure (<5%, 5-10%, >10%). Motility parameters (LES and esophageal body)
      were compared between the two groups. RESULTS: Of 349 patients who underwent
      manometry and pH testing during the study period, 133 were >or=65 yr old, and 48
      were <or=40 yr old. The degree of acid exposure was similar in both groups. The
      resting LES pressure was similar regardless of age but was lowest for both age
      groups in the patients with acid exposure > 10% (12.6 mm Hg in the <or=40-yr-old
      patients and 15.4 mm Hg in the >or=65-yr-old patients, p < 0.05). The percentage
      of swallows that induced normal peristalsis was lowest in the >or=65-yr-old
      patients compared with the <or=40-yr-old patients in the group with >10% acid
      exposure (62.5% vs 95%, p < 0.05). CONCLUSION: Reflux in older patients is
      complicated by disordered esophageal motility. This impaired motility may
      decrease acid clearance, result in more difficult to control disease, and may
      render these patients susceptible to GERD complications.

PMID- 12526934
TI  - Effect of different swallow time intervals on the nutcracker esophagus.
AB  - OBJECTIVE: Nutcracker esophagus (NE) is defined as the presence of peristaltic
      contractions in which the average distal esophageal amplitude is greater than 180
      mm Hg. The underlying mechanism responsible for these abnormalities is not known.
      The aim of this study was to test the hypothesis that NE might be caused by a
      defect in the inhibitory pathway controlling esophageal peristalsis. METHODS:
      Eight patients with NE (seven women, 1 man, mean age 50 yr) and eight age- and
      sex-matched normal volunteers (seven women, 1 man, mean age 48 yr) underwent a
      special protocol using three-channel (3, 8, and 16 cm above the lower esophageal
      sphincter) solid state esophageal manometry to evaluate deglutitive inhibition.
      Ten pairs of 5 ml of wet swallows were given at each of five different time
      intervals (30, 20, 15, 10, and 5 s). Pairs of swallows were spaced by 30 s, and
      different time intervals were spaced by 1 min. Tracings were recorded using a
      computer program and blindly automatically analyzed for both amplitude and
      duration of the contraction separately for the first and second swallow of each
      pair. Presence of deglutitive inhibition or muscle refractoriness was assessed
      according to interactions between the first and second swallow of the pair.
      Results were found abnormal when larger than the mean percent variation of the
      second and first swallow calculated for the 30-s interval, considered as baseline
      for each participant. Statistics included paired and nonpaired nonparametrical
      comparisons as appropriate. RESULTS: The median amplitude for the NE was 202 mm
      Hg (range 186-376) and for the controls was 118 mm Hg (range 64-167) (p =
      0.0002). The median duration in the NE group was 5.1 s (range 4-9.3) versus 4.1
      (range 3.3-5.0) for the controls (p = 0.02). The percent variation in duration (p
      = 0.31), amplitude (p = 0.42), and propagation velocity of the peristaltic waves
      (p = 0.69) did not differ between the control and NE groups. Peristalsis
      frequency dropped at the 5-s interval for both studied groups (p = 0.84).
      CONCLUSION: Central and local inhibitory mechanisms induced by closely timed
      swallows are preserved in the NE and do not explain the mechanism of the high
      amplitude and long duration contractions.

PMID- 12526935
TI  - Effect of proton pump inhibitors on the continuous real time (13)C-urea breath
      test.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of a new,
      continuous real time (13)C-urea breath test, BreathID, for the diagnosis of
      Helicobacter pylori in patients taking proton pump inhibitors (PPIs). METHODS:
      Fifty-two consecutive patients, positive for H. pylori by BreathID, were
      prospectively evaluated. Patients were randomized to receive either omeprazole 20
      mg/day or pantoprazole 40 mg/day for 14 days. A repeat breath test was performed
      on day 14 while patients received their last PPI pill. Patients were given a test
      drink containing 75 mg (13)C-urea and 4.0 g citric acid. Real time, continuously
      sampled expired (13)CO(2), obtained within 6-20 min, was compared with
      measurement of expired (13)CO(2) by isotope ratio mass spectrometry (IRMS).
      RESULTS: A full set of test data was available for 43 patients. After 14 days of
      treatment with PPIs, false negative detection of H. pylori occurred in only 1/43
      (2.3%) patients examined by continuous real time (13)C-urea breath test compared
      with 2/43 (4.6%) patients examined by IRMS. With the exception of one case,
      complete agreement was observed between BreathID and the IRMS breath tests at
      both baseline and after PPI treatment. PPI treatment was associated with three
      different types of responses on UBT: 1) one third of the patients developed a
      significant decrease in the (13)CO(2)/(12)CO(2) excretion, 2) roughly one third
      developed a significant increase in the post-PPI breath test results, and 3)
      results did not change significantly in the remaining patients. Linear regression
      analysis of 43 H. pylori-positive subjects indicated a significant positive
      association between baseline and post-PPI Delta (13)CO(2)/(12)CO(2) excretion.
      CONCLUSIONS: The use of a single test drink containing 4.0 g citric acid in
      BreathID, resulted in a low number of false negative results associated with
      sustained PPI treatment. Although there were some differences between BreathID
      versus IRMS, the type of PPI and the sampling method used do not appear to play a
      critical role in the detection of H. pylori by BreathID. According to these
      results, BreathID is a reliable tool for testing H. pylori in patients taking
      PPIs.

PMID- 12526936
TI  - Who is using chronic acid suppression therapy and why?
AB  - OBJECTIVES: Acid suppression medications have become one of the most commonly
      prescribed classes of therapeutic agents. Because little data exists describing
      the chronic use of these agents among a general population, we sought to
      determine the patterns of use of proton pump inhibitors (PPIs) and histamine type
      2 receptor antagonists (H2RAs) in clinical practice, as well as the distribution
      and severity of symptoms in patients prescribed these therapies. METHODS:
      Pharmacy billing data from two insurers were used to identify all patients on
      chronic (>90 days) PPIs and H2RAs within a large, eastern Massachusetts provider
      network. Patient demographics, diagnoses, frequency of office visits, and
      information about diagnostic testing were obtained from billing databases. A
      questionnaire addressing recent upper GI symptoms, over-the-counter medication
      use, and gastroenterologist consultations was mailed to a 1,139 patient subset
      (35%) of eligible patients. We compared the diagnoses of patients on chronic
      therapy with those of the general population of the network. We also compared the
      frequency of symptoms and diagnostic testing between those prescribed H2RAs and
      PPIs. RESULTS: From a total population of 168,727 adult patients, we identified
      4,684 (2.8%) prescribed chronic acid suppression therapy, with 47% taking H2RAs
      and 57% taking PPIs (4% filled prescriptions for both simultaneously). A relevant
      GI diagnosis was found using billing data for only 61% of patients, mainly for
      gastroesophageal reflux disease (38%) and dyspepsia (42%), with many patients
      carrying both diagnoses. Our survey (response rate 59%) revealed that more than
      30% of responders experienced heartburn or reflux more than twice a week, and
      more than half experienced symptoms of dyspepsia at least once a week. Diagnostic
      testing was uncommon, with only 19% having undergone esophagogastroduodenoscopy
      within the prior 2 yr. CONCLUSIONS: Acid suppression medications were used
      chronically by a large number of patients within this population. A significant
      proportion of patients on chronic PPI or H2RA lacked definitive upper GI
      diagnoses in their billing data. The high symptom burden and low use of
      diagnostic testing indicates opportunities for improvement in the care of
      patients on chronic acid suppression therapy.

PMID- 12526937
TI  - Diagnosis and management of gastrointestinal bleeding in patients with hereditary
      hemorrhagic telangiectasia.
AB  - OBJECTIVE: Our aim was to report our experience with treating GI bleeding in
      patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: Consecutive
      patients with GI bleeding referred to the Yale University Vascular Malformation
      Center underwent clinical evaluation and endoscopy. Hb and blood transfusion
      requirements for 1 yr before and after evaluation were documented. Patients with
      a mean Hb <or= 8 mg/dl or blood transfusion requirements >or= 12 units packed red
      blood cells (PRBC)/yr were defined as patients with significant bleeding. Drug
      therapies, including ethinyl estradiol/norethindrone, danazol, and aminocaproic
      acid, were prescribed on an individual patient basis. RESULTS: The study included
      43 HHT patients with a mean age of 57 yr. Endoscopy revealed telangiectases in
      the esophagus (1/41), stomach (33/41), duodenum (33/41), jejunum (5/9), and colon
      (10/32). Patients with > 20 telangiectases visualized on
      esophagogastroduodenoscopy had a significantly lower mean Hb of 7.9, compared
      with 9.4 (p = 0.007), and a trend toward higher blood transfusion requirements.
      Non-HHT-related causes of GI bleeding were diagnosed in four patients. During a
      mean follow up of 18.9 months, the group of 40 patients with HHT-related bleeding
      had improvements in their mean Hb and blood transfusion requirements.
      CONCLUSIONS: Some HHT patients with GI bleeding improve on drug therapies, but
      others fail. Transfusion-dependent GI bleeding is difficult to manage, and
      optimal management may include both medical and endoscopic treatments.

PMID- 12526938
TI  - Micturition is associated with phase III of the interdigestive migrating motor
      complex in man.
AB  - OBJECTIVES: In previous manometric studies, we observed that micturition was
      associated with phase III of the migrating motor complex. The present study aimed
      to objectify this possible relationship and to examine whether modulation of
      micturition frequency influences migrating motor complex phase III incidence.
      METHODS: In a retrospective study, ambulatory antroduodenal manometry and
      micturition data of 27 subjects were analyzed. In a prospective study,
      antroduodenal motility and micturition patterns were studied in five subjects who
      were subjected to an oral water load. Volunteers were either allowed to micturate
      ad libitum or instructed to postpone micturition. RESULTS: In the retrospective
      part of the study, a statistically significant association was found between
      phase III and micturition. Of all micturitions, 50% took place during or within
      10 min from phase III. Also, in the prospective part of the study, phase III and
      micturition, as well as micturition urge, showed a significant association (p <
      0.05). CONCLUSION: Micturition and phase III of the migrating motor complex are
      associated in time.

PMID- 12526939
TI  - Safety of extension of a previous endoscopic sphincterotomy: a prospective study.
AB  - OBJECTIVES: Data in the literature regarding complication risks after the
      extension of a previous endoscopic biliary sphincterotomy (repeat endoscopic
      biliary sphincterotomy) are limited and controversial. To explore this issue, we
      prospectively studied complications after repeat sphincterotomy and compared them
      with those of biliary endoscopic sphincterotomy in consecutive patients with
      choledocholithiasis. METHODS: A total of 250 patients underwent endoscopic
      biliary sphincterotomy and 81 underwent extension of a previous one. All patients
      had choledocholithiasis and were enrolled using specific criteria, excluding
      parameters predisposing to increased postsphincterotomy complications. RESULTS:
      The overall complication rate was 2.46% in the repeat sphincterotomy and 8.4% in
      the sphincterotomy group (p > 0.05). Complications for the repeat sphincterotomy
      and initial sphincterotomy groups, respectively, were as follows: bleeding, 2.46%
      and 2.8%; pancreatitis, 0% and 4.8% (p < 0.05); cholangitis, 0% and 0.4%;
      perforation, 0% and 0.4%; and hyperamylasemia, 3.7% and 12.8% (p < 0.05). There
      were no deaths. Bleeding episodes in the former group occurred when repeat
      sphincterotomy was performed early after the primary one. CONCLUSIONS: Repeat
      sphincterotomy is a safe technique for the treatment of patients with
      choledocholithiasis and seems to be as safe as initial sphincterotomy. It is not
      associated with increased hemorrhage risk. There is a trend toward a higher risk
      of hemorrhage when repeat sphincterotomy is performed early. Repeat
      sphincterotomy is safer than the initial sphincterotomy with respect to
      pancreatic complications.

PMID- 12526940
TI  - Surveillance cultures to monitor quality of gastrointestinal endoscope
      reprocessing.
AB  - OBJECTIVES: High-level disinfection of GI endoscopes can be reliably obtained
      under controlled conditions with approved reprocessing methods. However, there
      are scant data regarding the effectiveness of these methods in clinical practice
      and no published methods of verification. The purpose of this study is to review
      retrospectively the results of environmental cultures of flexible endoscopes and
      to analyze the pattern of results. METHODS: Cultures of selected GI endoscopes
      listed as ready to use were obtained by adding 5-15 ml of trypticase soy broth or
      saline or 30-50 ml of sterile water to the biopsy channel of an endoscope. This
      wash was collected in a sterile container, plated onto blood and MacConkey agar,
      incubated at 37 degrees C, and examined for growth at 24 and 48 h. Personnel
      trained in accordance with approved procedures performed endoscope reprocessing.
      RESULTS: A total of 312 surveillance cultures were performed between 1990 and
      1999. Initially, three of 17 water bottles were found to be contaminated with
      Pseudomonas species. The bottles were sterilized daily; only sterile water was
      used and subsequent cultures were negative. Between 1992 and 1994, 15/129 (11.6%)
      cultures were positive; 14 (93%) were from duodenoscopes. From 1995 to 1997,
      18/124 (14.5%) cultures were positive, but only six (33%) were from
      duodenoscopes. However, 10 (55.6%) positive cultures were obtained from
      therapeutic upper endoscopes, attributed to faulty mechanical cleaning by
      nonnursing personnel after emergent procedures. The reprocessing procedure was
      altered, with improvement. One duodenoscope was persistently culture positive and
      was found to have a damaged biopsy channel. There were no recognized iatrogenic
      infections associated with endoscopic procedures. Organisms cultured were
      commonly gram-negative rods. CONCLUSIONS: The use of environmental endoscope
      culturing is a rapid, simple, inexpensive method to monitor effectiveness of
      standard reprocessing procedures. Disinfection is less effective with poor
      mechanical cleansing, and high-titer positivity is a marker for poor cleaning
      technique. Standard upper and lower scopes are commonly culture negative.
      Duodenoscopes, because of their inherent complexity, and other scopes used in
      emergent conditions require particular attention. Surveillance culture results
      can be used to identify patterns of poor technique, to reinforce proper
      procedure, and to modify clinical practice. No associated clinical illness was
      apparent during this study.

PMID- 12526941
TI  - Yield of dual endoscopy for positive fecal occult blood test.
AB  - OBJECTIVES: Dual endoscopy is frequently performed on the same day in patients
      whose stools are found to be positive on fecal occult blood testing (FOBT). This
      is often done to localize the potential sources of GI bleed. The diagnostic yield
      of same day dual upper endoscopy (EGD) and lower endoscopy (colonoscopy) for the
      detection of positive FOBT is uncertain. In the era of cost-efficient medical
      practice, we investigated whether a more evidence-based and structured approach
      could be used to guide physicians to the workup of patients who present with
      positive FOBT. METHODS: We performed a retrospective analysis of 309 patients,
      and 260 patients from this population met our inclusion criteria. Inclusion
      criteria included FOBT without acute GI hemorrhage, hematochezia, or melena.
      Patients were required to have had EGD and colonoscopy within the same day (<24
      h). RESULTS: Of 260 patients, a total of 135 (52%) patients had positive findings
      on colonoscopy and a total of 42 (16.1%) patients had positive findings on EGD.
      Sixteen (6.1%) had positive EGD and negative colonoscopy; 109 (42%) had positive
      colonoscopy and negative EGD; and 26 (10%) had positive findings on both EGD and
      colonoscopy. CONCLUSIONS: Colonoscopy should be chosen as the initial procedure
      of choice in the evaluation of patients who present with positive FOBT. Same day
      dual endoscopy does not seem to be cost-effective.

PMID- 12526942
TI  - Minimizing recurrent peptic ulcer hemorrhage after endoscopic hemostasis: the
      cost-effectiveness of competing strategies.
AB  - OBJECTIVES: Controversy exists regarding the optimal strategy to minimize
      recurrent ulcer hemorrhage after successful endoscopic hemostasis. Our objective
      was to evaluate the cost-effectiveness of competing strategies for the
      posthemostasis management of patients with high risk ulcer stigmata. METHODS:
      Through decision analysis, we calculated the cost-effectiveness of four
      strategies: 1) follow patients clinically after hemostasis and repeat endoscopy
      only in patients with evidence of rebleeding (usual care); 2) administer
      intravenous proton pump inhibitors (i.v. PPIs) after hemostasis and repeat
      endoscopy only in patients with clinical signs of rebleeding; 3) perform second
      look endoscopy at 24 h in all patients with successful endoscopic hemostasis; and
      4) perform selective second look endoscopy at 24 h only in patients at high risk
      for rebleeding as identified by the prospectively validated Baylor Bleeding
      Score. Probability estimates were derived from a systematic review of the medical
      literature. Cost estimates were based on Medicare reimbursement. Effectiveness
      was defined as the proportion of patients with rebleeding, surgery, or death
      prevented. RESULTS: The selective second look endoscopy strategy was the most
      effective and least expensive of the four competing strategies, and therefore
      dominated the analysis. The i.v. PPI strategy required 50% fewer endoscopies than
      the competing strategies, and became the dominant strategy when the rebleed rate
      with i.v. PPIs fell below 9% and when the cost of i.v. PPIs fell below 10
      dollars/day. CONCLUSIONS: Compared with the usual practice of "watchful waiting,"
      performing selective second look endoscopy in high risk patients may prevent more
      cases of rebleeding, surgery, or death at a lower overall cost. However, i.v.
      PPIs are likely to reduce the need for second look endoscopy and may be preferred
      overall if the rebleed rate and cost of i.v. PPIs remains low.

PMID- 12526943
TI  - Conservative management of infected necrosis complicating severe acute
      pancreatitis.
AB  - OBJECTIVES: Patients with severe necrotizing pancreatitis are at risk for
      infection, a major cause of morbidity and mortality. Most patients with infected
      pancreatic tissue require surgical intervention (necrosectomy), which is
      associated with high morbidity and mortality. A subset of these patients can be
      managed successfully with conservative management combined with prolonged courses
      of antibiotics. METHODS: Three cases of severe acute pancreatitis seen at our
      institution are described, in which the patients developed aspirate-proven
      pancreatic infections. The patients were nonetheless stable from a clinical
      standpoint and were treated with long courses of antibiotics known to penetrate
      the pancreas; emergent surgery was deferred. RESULTS: In two patients, surgery
      was completely avoided, with good clinical outcome. In the third patient,
      elective surgery was undertaken 12 wk after the episode of acute pancreatitis, to
      perform necrosectomy on organized pancreatic necrosis and to evaluate the
      patient's biliary tree. There were no postoperative complications. CONCLUSIONS: A
      subset of patients with severe acute pancreatitis complicated by infection can be
      successfully managed with long term antibiotics and other supportive measures.
      High risk necrosectomy can, in some instances, be delayed or avoided entirely.

PMID- 12526944
TI  - Safety and steroid-sparing experience using infliximab for Crohn's disease at a
      pediatric inflammatory bowel disease center.
AB  - OBJECTIVES: The published experience using infliximab (Remicade, Centocor,
      Malvern, PA) for the treatment of pediatric Crohn's disease is limited but
      suggests utility in the treatment of refractory disease. Experience using
      infliximab at a large pediatric center is reviewed. METHODS: A retrospective
      review of all infliximab infusions administered to patients with Crohn's disease
      (CD) was undertaken. Data were obtained from database and pharmacy records. Chart
      review and interviews with physicians, patients, and families were used to obtain
      missing data. RESULTS: A total of 432 infusions were administered to 82 patients
      (34 female and 48 male) with CD. The number of infusions each patient received
      ranged from one to 18, with a mean of 5.3 (SD 4.6) and median of 3. Of 33
      patients, 19 (57.6%) became independent and remained free of corticosteroids.
      There was a statistically significant difference in the steroid dose between 0
      and 4 wk and 0 and 8 wk. In all, 23 infusion reactions occurred (5.3%). Three
      patients developed herpes zoster, and one developed Listeria monocytogenes
      meningitis. No patients were documented to have delayed hypersensitivity
      reactions or malignancies. CONCLUSIONS: Infliximab is safe and effective for
      treating pediatric patients with CD. A steroid-sparing effect was demonstrated.
      The most common adverse reaction to infliximab was infusion reaction. These
      reactions did not preclude further use of the agent. Serious infections were seen
      in a small number of patients.

PMID- 12526945
TI  - Low vitamin B(6) plasma levels, a risk factor for thrombosis, in inflammatory
      bowel disease: role of inflammation and correlation with acute phase reactants.
AB  - OBJECTIVES: Individuals with inflammatory bowel disease (IBD) are at increased
      risk for thrombosis and vitamin deficiencies. Low plasma levels of vitamin B(6)
      are an independent risk factor for thrombosis and may cause hyperhomocysteinemia,
      another recognized risk factor for thrombosis. The aim of this study was to
      evaluate vitamin B(6) plasma levels in IBD patients. METHODS: We studied 61 IBD
      patients: 32 with Crohn's disease and 29 with ulcerative colitis. For each
      patient, three sex- and age-matched healthy control subjects were studied.
      RESULTS: Median vitamin B(6) levels were significantly lower in IBD patients
      (22.0 pmol/L, range 3.6-231.0) than in controls (31.1 pmol/L, 3.7-363.4; p <
      0.01). In all, 13.1% IBD patients and 5.5% controls had plasma vitamin B(6)
      levels lower than the 5th percentile of distribution in normal controls (p <
      0.05). Low vitamin B(6) levels were significantly more frequent in patients with
      active disease than in patients with quiescent disease (seven of 26, 26.9%, vs
      one of 35, 2.9%; p < 0.001). Moreover, patients with active disease had
      significantly lower median vitamin B(6) levels (13.4 pmol/L, range 3.6-124.0)
      than patients in a quiescent phase (27.0 pmol/L, 7.8-231.0; p < 0.001). Low
      vitamin B(6) levels were significantly correlated with serum concentrations of C
      reactive protein (r = -0.36, 95% CI = -0.59 to -0.09, p < 0.01) and alpha(1)-acid
      glycoprotein (r = -0.37, 95% CI = -0.59 to -0.10, p < 0.01). Hyperhomocysteinemia
      was more frequent in patients with low vitamin B(6) levels (three of eight,
      37.5%) than in patients with normal levels (nine of 53, 17.0%; p = 0.18). There
      was no statistically significant correlation between vitamin B(6) and
      homocysteine plasma levels (r = -0.13, 95% CI = -0.37 to +0.14, p = 0.33).
      CONCLUSIONS: Low vitamin B(6) plasma levels, an independent risk factor for
      thrombosis, are frequent in patients with IBD, especially those with active
      disease.

PMID- 12526946
TI  - Duodenal pathology and clinical-immunological implications in common variable
      immunodeficiency patients.
AB  - OBJECTIVES: Common variable immunodeficiency (CVID) is an immunological disorder
      characterized by defective antibody production. An increased prevalence of celiac
      disease has been suggested in patients with this disorder. This study aimed to
      assess duodenal pathology and its clinical implications in these patients.
      METHODS: A total of 32 consecutive CVID patients with anemia or GI symptoms were
      enrolled. Patients underwent upper endoscopy, and biopsy specimens were taken in
      the descending duodenum for histological assessment. A blood sample was obtained
      to determine immunoglobulin and Hb levels and to evaluate the CD4+ T-lymphocyte
      count. Body mass index was calculated for all patients. RESULTS: Histological
      assessment of duodenal specimens revealed the presence of villous atrophy in 10
      (31.2%) patients, a feature of nodular lymphoid hyperplasia in five (15.6%), and
      mild duodenitis in two (6.3%), whereas normal histology was observed in the
      remaining 15 (46.9%) patients. Patients with villous atrophy had anemia more
      frequently than those without, whereas the frequency of persistent diarrhea did
      not differ between these two groups. Moreover, both CD4 levels and body mass
      index were significantly lower in patients with atrophy than in controls.
      CONCLUSIONS: Duodenal villous atrophy is very frequent in symptomatic CVID
      patients, with relevant clinical and immunological implications. Specifically,
      this histological alteration is significantly associated with anemia,
      malnutrition, and low blood CD4+ lymphocyte levels.

PMID- 12526947
TI  - Outcome measures in irritable bowel syndrome: comparison of psychometric and
      methodological characteristics.
AB  - OBJECTIVES: Although there is growing interest in irritable bowel syndrome (IBS)
      research, there is as yet no consensus regarding the preferred outcome measure.
      We aimed to evaluate and to compare the validity and appropriateness of available
      IBS outcome measures. METHODS: IBS symptom and IBS health-related quality of life
      (HRQOL) scales were identified through a literature search. In a panel
      evaluation, six reviewers independently rated the scales according to
      predetermined psychometric and methodological validation criteria. RESULTS: Five
      IBS symptom scales and five IBS HRQOL instruments were identified. Two of the
      symptom scales were rated as good. The Adequate Relief question scored best. This
      scale demonstrates responsiveness as well as face and construct validity, and its
      score was considered easy to interpret and appropriate for use. According to the
      reviewers, the IBS Severity Scoring System performed well with regard to
      psychometric capacities, but its practical utility was considered debatable. The
      properties of the other three symptom scales were suboptimal. The practical
      utility of the five IBS-specific HRQOL scales was considered poor. However, the
      reviewers agreed that, at present, the IBS Quality of Life measurement (Patrick
      et al.) is the best choice, because it has been the most extensively validated
      and shows appropriate psychometric quality. CONCLUSIONS: The Adequate Relief
      question is the measure of first choice when assessing global symptomatology as
      an outcome in IBS studies. For a more detailed IBS symptom assessment, the IBS
      Severity Scoring System is preferable. Finally, the IBS Quality of Life
      measurement scale can be used to establish changes in health-related quality of
      life.

PMID- 12526948
TI  - Decreased colonic motility in persons with chronic spinal cord injury.
AB  - OBJECTIVES: In persons with spinal cord injury (SCI), several studies have shown
      that large bowel transit is decreased at the level of the left colon and rectum,
      and that postprandial colonic response to food is absent. To define these
      parameters further, the effects of food on colonic motility in persons with SCI
      were studied and compared to those of spinally intact (SI) individuals. METHODS:
      The study was conducted in eight subjects with SCI (four paraplegic and four
      quadriplegic) and six age-matched SI subjects. After routine bowel preparation,
      colonoscopy was performed with the proximal end of a solid state pressure
      transducer catheter (four sensors each separated by 10 cm) tethered to the
      splenic flexure using endoclips (Olympus). The subjects were then allowed to
      carry out their usual daily activities. Two phases were compared: 1 h before
      breakfast, designated as the "resting phase," and 1 h during breakfast,
      designated as the "food-ingestion phase." RESULTS: Baseline colonic activity of
      the SCI group was significantly less than in SI subjects. During meals, the
      motility index, mean amplitude of the waves, percent activity, and number of
      waves was significantly less in the SCI group. In both the SI and SCI groups, a
      postprandial colonic response was observed. However, in the SCI group, the
      response was seen only in the descending colon and not in the rectosigmoid
      region. CONCLUSIONS: SCI decreases colonic motility, and this alteration may
      relate to difficulty with evacuation. The postprandial colonic response in SCI is
      present but is suboptimal and confined to the descending colon.

PMID- 12526949
TI  - Irritable bowel syndrome patients show enhanced modulation of visceral perception
      by auditory stress.
AB  - OBJECTIVES: Symptoms in irritable bowel syndrome (IBS) patients are sensitive to
      psychological stressors. These effects may operate through an enhanced
      responsiveness of the emotional motor system, a network of brain circuits that
      modulate arousal, viscerosomatic perception, and autonomic responses associated
      with emotional responses, including anxiety and anger. The aim of this study was
      to test the primary hypothesis that IBS patients show altered perceptual
      responses to rectal balloon distention during experimentally induced
      psychological stress compared with healthy control subjects. METHODS: A total of
      15 IBS patients (nine women and six men) and 14 healthy controls (seven women and
      seven men) were studied during two laboratory sessions: 1) a mild stress
      condition (dichotomous listening to two conflicting types of music), and 2) a
      control condition (relaxing nature sounds). The stress and relaxation auditory
      stimuli were delivered over a 10-min listening period preceding rectal
      distentions and during the rectal distentions but not during the distention
      rating process. Ratings of intensity and unpleasantness of the visceral
      sensations, subjective emotional responses, heart rate, and neuroendocrine
      measures (norepinephrine, cortisol, adrenocorticotropic hormone [ACTH], and
      prolactin) were obtained during the study. RESULTS: IBS patients, but not healthy
      controls, rated the 45-mm Hg visceral stimulus significantly higher in terms of
      intensity and unpleasantness during the stress condition compared with the
      relaxation condition. IBS patients also reported higher ratings of stress, anger,
      and anxiety during the stress compared with the relaxing condition, whereas
      controls had smaller and nonsignificant subjective responses. Heart rate
      measurements, but not other neuroendocrine stress measures, were increased under
      the stress condition in both groups. CONCLUSION: These findings confirm the
      hypothesis of altered stress-induced modulation of visceral perception in IBS
      patients.

PMID- 12526950
TI  - Cytokine gene polymorphisms in patients infected with hepatitis B virus.
AB  - OBJECTIVE: Cytokines play a key role in the regulation of the immune response.
      The maximal capacity of cytokine production varies among individuals and
      correlates with the polymorphism in the cytokine gene promoters. The aim of this
      study was to characterize gene polymorphism in patients with chronic hepatitis B
      virus (HBV) infection and to determine the different patterns in patient
      subgroups. METHODS: The study population consisted of 77 patients with chronic
      HBV infection (23 low-level HBV replicative carriers, 23 compensated high-level
      HBV replicative carriers, 21 decompensated liver transplant candidates, and 10
      patients with documented hepatocellular carcinoma). The genetic profile of five
      cytokines was analyzed by polymerase chain reaction-sequence-specific primer
      (SSP), and subjects were genotyped as high or low producers of tumor necrosis
      factor-alpha and interleukin (IL)-6, and as high, intermediate, or low producers
      of transforming growth factor-beta(1), interferon (IFN)-gamma, and IL-10 based on
      single nucleotide substitutions. The control group included 10 healthy
      individuals who recovered from HBV infection and 48 healthy controls. RESULTS: A
      highly statistically significant difference in the distribution of the IFN-gamma
      gene polymorphism (at position +879) was observed between patients with chronic
      HBV infection and controls. The majority of the patients (65.2%) exhibited the
      potential to produce low levels of IFN-gamma (A/A genotype) compared with 37.5%
      of the control group (p = 0.003). Healthy individuals who recovered from HBV
      infection had a similar distribution of IFN-gamma gene polymorphism as the
      healthy controls. No statistically significant difference in IFN-gamma production
      was found between patients with low- and high-level HBV replication and between
      compensated and decompensated patients. There was also no statistically
      significant difference in the genetic ability to produce tumor necrosis factor
      alpha (at position -308), IL-6 (at position -174), IL-10 (at position -1082, 
      819, and -592), and transforming growth factor-beta(1) (at position +10 and +25).
      CONCLUSION: These findings suggest an association between the genetic ability to
      produce low levels of IFN-gamma and the susceptibility to develop chronic HBV
      infection.

PMID- 12526951
TI  - Genotypic and phenotypic resistance: longitudinal and sequential analysis of
      hepatitis B virus polymerase mutations in patients with lamivudine resistance
      after liver transplantation.
AB  - OBJECTIVE: Lamivudine-resistant strains appear in 27-62.5% of liver transplant
      recipients treated with lamivudine for hepatitis B virus (HBV) recurrence, and
      may lead to failure of antiviral therapy. In an extension of our previous study,
      we investigated the molecular events associated with the emergence of lamivudine
      resistant mutants in this population. METHODS: Sequential serum samples from 10
      consecutive patients with lamivudine resistance after liver transplantation were
      analyzed for viral genotype, precore mutants, and viral polymerase gene mutants
      (L528M, M552V, M552I) using restriction fragment length polymorphism.
      Quantitative analysis of HBV DNA was performed using hybridization assay and
      polymerase chain reaction. RESULTS: Eight patients (80%) were infected with
      genotype D and two (20%) with genotype C. Polymerase mutants (genotypic
      resistance) were identified in all the patients. Phenotypic resistance (rise in
      serum HBV DNA titers above the detection limit of the hybridization assay)
      developed in five patients (50%); of the remainder, three (30%) did not have
      phenotypic resistance, and two were primary nonresponders. Genotypic resistance
      was detected earlier than phenotypic resistance (median 285 days [range 42-510]
      vs median 387 days [range 320-420], p = 0.055). In five patients (50%), the
      emergence of the YMDD mutants took over the wild type; in three (30%), the YMDD
      mutant took over the wild type, but the wild type re-emerged during lamivudine
      therapy; and in two (20%), the YMDD mutants were detected in a mixture with the
      wild type (in different percentages). The mean pretreatment serum ALT level was
      significantly lower in the patients who did not develop phenotypic resistance (p
      = 0.0002). The M552I pure viral population was found mainly in these patients,
      and all retained stable graft function (median follow-up 33 months). A high
      pretreatment HBV DNA level (>50 x 10(6) copies/ml) was highly statistically
      significantly correlated with the rapid occurrence of phenotypic resistance (r = 
      0.90, p = 0.04). CONCLUSIONS: We reached the following conclusions: 1) In our
      area, liver transplant recipients who develop resistance to lamivudine given for
      recurrent HBV infection seem to be mainly infected with genotype D. 2) Re
      emergence of the wild type can occur during lamivudine therapy. 3) Genotypic
      resistance precedes phenotypic resistance, although phenotypic resistance does
      not always follow genotypic resistance. 4) Quantitative determination of viremia
      and analysis of polymerase gene mutants are recommended for monitoring antiviral
      therapy of liver transplant patients with HBV reinfection in the graft.

PMID- 12526952
TI  - Influence of TNF gene polymorphism and HLA-DRB1 haplotype in Japanese patients
      with chronic liver disease caused by HCV.
AB  - OBJECTIVE: To clarify the host genomic role in chronic liver disease associated
      with hepatitis C virus (HCV), we investigated the relationship between the
      severity of hepatitis and the polymorphisms of the tumor necrosis factor (TNF)
      gene or the human leukocyte antigen (HLA)-DRB1 haplotypes. METHODS: We analyzed
      40 healthy subjects, 50 patients with chronic inactive hepatitis caused by HCV
      with mean serum ALT concentrations under 40 IU/ml (group A), and 50 patients with
      chronic active liver disease caused by HCV and mean ALT concentrations over 50
      IU/ml (group B). RESULTS: There were no significant differences in the
      frequencies of TNF promoter gene variants at positions -238 and -308 between the
      groups. Regarding polymorphisms at the TNF-beta NcoI site, the frequency of B1B1
      homozygotes in group A was significantly increased, compared with the healthy
      subjects and those in group B (controls 7.5%, group A 34%, group B 10%).
      Regarding the analysis of HLA-DRB1, DRB1*0901 was significantly more frequent in
      group A than in group B (group A 19%, group B 5%). TNF B1B1 homozygotes were
      associated with HLA-DRB1*0901 and *1302, and negatively associated with
      DRB1*0405. Combination analysis revealed that HCV was inactive in the majority of
      patients who were both DRB1*0901 and B1B1 homozygotes. CONCLUSION: Our data
      suggest that TNF gene polymorphisms and HLA-DRB1 haplotype may influence the
      activity of HCV in chronic liver disease.

PMID- 12526953
TI  - Association between hepatitis C infection and other infectious diseases: a case
      for targeted screening?
AB  - OBJECTIVE: Hepatitis C virus (HCV) shares risk factors and routes of transmission
      with several other infectious agents. However, the prevalence of comorbid
      infectious disorders among HCV-infected patients remains unknown. To analyze the
      association between HCV and several categories of infectious disorders, we
      carried out a case-control study using information from 172 hospitals contained
      in the computerized databases of the Department of Veterans Affairs. METHODS: We
      identified all HCV-infected patients who were hospitalized during 1992-1999. For
      each case, four control subjects without HCV were randomly chosen from
      hospitalized patients and were matched with cases on the year of admission. The
      frequencies of several predefined infectious disease diagnoses were compared
      between cases and control subjects, and the strength of these associations were
      assessed in multivariable logistic regression analyses. RESULTS: We identified
      34,204 HCV-infected patients (cases) and 136,816 control subjects without HCV.
      Patients in the case group were younger (48.4 yr vs 59.8 yr), were more
      frequently nonwhite (38.5% vs 26.5%), and were more likely to have served in
      Vietnam (68.1% vs 33.0%); all p < 0.0001. Compared with control subjects,
      patients with HCV had a significantly higher prevalence of other blood-borne
      virus infections, including HIV (14.1% vs 3.0%) and hepatitis B (22.4% vs 0.7%);
      immunodeficiency-related infections, including cytomegalovirus (0.6% vs 0.2%),
      toxoplasmosis (0.3% vs 0.1%), cryptococcosis (0.4% vs 0.1%), and tuberculosis
      (3.3% vs 1.3%); sexually transmitted diseases, including gonococcus (0.5% vs
      0.1%), chlamydia (1.6% vs 0.7%), syphilis (2.0% vs 0.6%), and genital herpes
      (1.0% vs 0.3%); and bacterial infection, including peritonitis, sepsis,
      endocarditis, cellulitis, and carbuncles (all p < 0.0001). After excluding
      potentially immunocompromised patients, including those with HIV, organ
      transplant, and cirrhosis, HCV remained significantly associated with CMV,
      cryptococcus, tuberculosis, and sexually transmitted diseases. Similar results
      were obtained when the analyses were restricted to Vietnam-era veterans.
      CONCLUSIONS: Several infectious diseases are more common among HCV-infected
      patients compared with those without HCV infection. These findings support an
      approach of targeted screening for HCV among patients with these infectious
      diseases.

PMID- 12526954
TI  - Incidence of idiopathic acute liver failure and hospitalized liver injury in
      patients treated with troglitazone.
AB  - OBJECTIVE: Troglitazone, a thiazolidinedione antidiabetic agent, was withdrawn
      from the U.S. market in March, 2000, after 94 cases of acute liver failure (ALF)
      were reported with its use. Based on a literature review, the estimated
      background rate of hospitalization for idiopathic acute liver injury is 22 per
      million person-years and for idiopathic ALF, less than 1 per million person
      years. This study was conducted to estimate the incidence rates of hospitalized
      idiopathic acute liver injury and ALF among troglitazone-treated patients.
      METHODS: An observational retrospective inception cohort of patients treated with
      troglitazone was assembled using claims data from a large multistate health care
      organization. Patients with at least 90 days of health plan enrollment before
      their first troglitazone prescription between April, 1997 and December, 1998 were
      enrolled. Hospitalized cases of potential troglitazone-induced acute liver injury
      or ALF were identified from claims data based on International Classification of
      Diseases, 9th Revision, coding. Primary medical records were reviewed for case
      validation, and incidence rates of acute liver injury were calculated using
      person-years of troglitazone exposure as the denominator. RESULTS: A total of
      7568 patients contributed 4020 person-years of troglitazone exposure. Of these,
      five were hospitalized with acute liver injury attributed to the drug and not
      explained by other causes. Incidence rates (95% CI) per million person-years of
      acute idiopathic liver injury were as follows: hospitalization (n = 5), 1244
      (404, 2900); hospitalized jaundice (n = 4), 995 (271, 2546); and ALF (n = 1), 240
      (6.3, 1385). CONCLUSIONS: Troglitazone use was associated with a marked increase
      in risk of hospitalized acute idiopathic liver injury and ALF.

PMID- 12526955
TI  - Nitric oxide synthase inhibition does not improve renal function in cirrhotic
      patients with ascites.
AB  - OBJECTIVES: Based mainly on animal experiments, nitric oxide (NO) has been
      proposed to account for the peripheral arterial vasodilation and hyperdynamic
      circulation in liver cirrhosis. The aim of this study was to clarify whether a
      reduction of NO synthesis would ameliorate the circulatory and renal dysfunction
      in decompensated cirrhotic patients. METHODS: The effects of N(G)-monomethyl-L
      arginine-acetate (L-NMMA), an NO synthesis inhibitor, were studied. After a 60
      min basal period, a total of 10 patients received increasing doses of L-NMMA,
      five patients (Low) received 12.5, 25, and 50 microg/kg/min, and five patients
      (High) received 25, 50, and 100 microg/kg/min as a constant infusion during 3 h,
      followed by a postinfusion period. Five patients (Placebo) received saline
      infusions only. Glomerular filtration rate and renal plasma flow were measured by
      clearance techniques with (99m)Tc-diethylenetriamine-pentaacetate and (131)I
      Hippuran. RESULTS: L-NMMA infusion resulted in an increased blood pressure,
      decreased heart rate, and dose-dependent suppression of renin of up to 42.1 +/-
      7.1% (p < 0.01) and angiotensin II of up to 39.9 +/- 9.6%, (p < 0.01) levels.
      Sodium and water excretion were not improved, most likely because of a reduction
      in renal blood flow of up to 29.1 +/- 8.1% (p < 0.01). CONCLUSION: Despite a
      partial correction of the hyperdynamic circulation, inhibition of NO synthesis
      does not improve sodium and water excretion in decompensated cirrhosis, probably
      because of an accompanying decrease in renal plasma flow. Intrarenal NO synthesis
      may be important for maintaining intrarenal hemodynamics in decompensated
      cirrhotic patients.

PMID- 12526956
TI  - Methotrexate therapy for primary biliary cirrhosis.
AB  - OBJECTIVE: Preliminary data suggested possible benefits of methotrexate in
      primary biliary cirrhosis. We assessed the effectiveness of methotrexate use in
      primary biliary cirrhosis and its tolerance in patients with this disease.
      METHODS: A total of 110 primary biliary cirrhosis patients began methotrexate 15
      mg/wk; for most, ursodeoxycholic acid was added during the study. We analyzed
      data from patients completing 5 yr of treatment with methotrexate to assess its
      effect on biochemical and histologic parameters after 5 yr of therapy. Based on
      an intent to treat analysis, we also compared survival of our patients (n = 110)
      with that of patients in a previously published, placebo-controlled trial of
      ursodeoxycholic acid (n = 180). RESULTS: Only half of the study group completed 5
      yr of methotrexate therapy. Therapy did not prevent progression of disease, as
      indicated by a rising Mayo risk score. Portal fibrosis tended to remain the same.
      Methotrexate did not diminish the risk of death or liver transplantation when
      compared with ursodeoxycholic acid or placebo; however, ursodeoxycholic acid use
      decreased the risk of death or transplant (p = 0.006). CONCLUSIONS: Methotrexate
      is not well tolerated in primary biliary cirrhosis. The toxicity of methotrexate
      and its inability to prevent complications of progressive liver disease or
      improve survival and the need for liver transplantation limits its utility. The
      benefits of ursodeoxycholic acid were again confirmed.

PMID- 12526957
TI  - Volume and yield of screening colonoscopy at a tertiary medical center after
      change in medicare reimbursement.
AB  - OBJECTIVE: Starting July 1, 2001, Medicare began to reimburse for screening
      colonoscopy in asymptomatic adults older than 50 yr with no risk factors for
      colorectal cancer. We sought to determine the short-term impact of the change in
      Medicare reimbursement on the demand for and yield of screening colonoscopy at
      our tertiary institution. METHODS: Asymptomatic patients older than 50 referred
      for first screening colonoscopy after the change in Medicare reimbursement from
      July 1, 2001 to December 31, 2001 were compared with a similar cohort screened
      before Medicare coverage for a family history of cancer or polyps during the same
      months the previous year (July 1, 2000 to December 31, 2000). Patient
      demographics, number, size, location, and histology of polyps/cancers for these
      screening colonoscopies were collected. RESULTS: A total of 1282 colonoscopies
      were performed in our institution from July 1, 2001 to December 31, 2001, 257
      (20%) for screening. During the same months in the previous year, 121 of 938
      colonoscopies (12.9%) were for screening (p < 0.01). This was a 55% increase in
      the percentage of colonoscopies performed for screening, and a 112% increase in
      the number of screening colonoscopies. Patients screened after the change in
      Medicare reimbursement were on average 5 yr older compared with patients of the
      previous year (62 +/- 10 [mean +/- SD] vs 56 +/- 9 yr; p < 0.01). A total of 61
      screening colonoscopies (24%) performed after the change in Medicare
      reimbursement had adenomatous lesions, compared with 25 (21%) screened for family
      history (p = ns). The number of adenomas 10 mm or larger or cancers did not
      differ significantly between the two groups (17 in 2001 vs 12 in 2000; p = ns).
      Age of 65 or older was associated with detection of adenomatous lesions (OR =
      1.7; 95% CI = 1.01-2.9013). CONCLUSIONS: Since the change in Medicare
      reimbursement, there has been a significant increase in the number and proportion
      of colonoscopies performed for screening at our institution. Patients screened
      since this change are older, and the detection rate of neoplastic lesions is
      similar to those previously screened for a family history of colorectal cancer or
      polyps.

PMID- 12526958
TI  - Hemoglobinometer.

PMID- 12526959
TI  - Budd-Chiari syndrome and hepatocellular carcinoma: a case report and review of
      the literature.
AB  - Acid suppression medications have become A 62-yr-old woman with a long-standing
      history of presumed cryptogenic cirrhosis was referred for evaluation of an
      elevated bilirubin level. Workup showed an elevated alpha-fetoprotein level, and
      a mass in the liver was detected by imaging studies; this was confirmed as
      hepatocellular carcinoma by biopsy. Her past medical history was significant for
      a portocaval shunt procedure 30 yr prior; a wedge biopsy obtained at that time
      had been interpreted as postnecrotic cirrhosis, but upon current review, lesions
      of acute and chronic venous outflow obstruction consistent with Budd-Chiari
      syndrome were noted. This case is unusual in two aspects: the patient survived 30
      yr after shunt surgery with undiagnosed Budd-Chiari syndrome; and the association
      of Budd-Chiari syndrome with subsequent hepatocellular carcinoma is uncommon.

PMID- 12526960
TI  - Efficacy of colchicine in patients with primary biliary cirrhosis poorly
      responsive to ursodiol and methotrexate.
AB  - OBJECTIVE: Approximately 20-30% of patients with primary biliary cirrhosis (PBC)
      respond fully to treatment with ursodeoxycholic acid (UDCA). The rest have
      progressive disease and eventually develop cirrhosis and liver failure. More
      effective treatment is needed. Methotrexate improved biochemical tests of liver
      function and liver histology in patients with PBC who had failed to respond to
      UDCA in one report and induced sustained biochemical and histological remission
      in another. The role of colchicine in PBC is unclear. We describe three patients
      with symptomatic PBC who responded very well to the addition of colchicine after
      they had failed to respond to UDCA alone and in combination with methotrexate. We
      suggest that colchicine should be tried in PBC patients who clearly fail to
      respond to UDCA. METHODS: Three patients with symptomatic biopsy-proven,
      antimitochondrial antibody-positive PBC failed to respond to UDCA and then to the
      addition of methotrexate. Colchicine was eventually added to the regimen.
      Symptoms, biochemical tests of liver function, and percutaneous liver biopsies
      were done at baseline, after treatment with UDCA, UDCA plus methotrexate, and
      UDCA plus methotrexate plus colchicine. RESULTS: All three patients responded
      after colchicine was added to UDCA and methotrexate. Symptoms, biochemical tests
      of liver function, and liver histology improved in all, and blood tests
      normalized in two. CONCLUSIONS: Colchicine may be effective treatment in some
      symptomatic patients with PBC who respond incompletely to UDCA alone or in
      combination with methotrexate. Colchicine may be tried in such patients.

PMID- 12526961
TI  - Filling is believing...?

PMID- 12526962
TI  - CT colonography to detect colorectal polyps: a virtual success?

PMID- 12526963
TI  - MR imaging of Crohn's disease: what is the attraction?

PMID- 12526964
TI  - Re: Gupta et al.--Juvenile polyps in the colon.

PMID- 12526966
TI  - Does acid suppression alter progression in Barrett's esophagus?

PMID- 12526968
TI  - Caution in the interpretation of safety and efficacy differences in clinical
      trials comparing aminosalicylates for ulcerative colitis.

PMID- 12526969
TI  - Treatment of ulcerative colitis with balsalazide: response to editorial by Drs.
      Farrell and Peppercorn and letter to the editor by Dr. Hanauer.

PMID- 12526970
TI  - Chylous ascites.

PMID- 12526971
TI  - Isolated cecal varices as the source of massive lower GI bleeding in a patient
      with cirrhosis.

PMID- 12526972
TI  - Thalidomide for the treatment of bleeding angiodysplasias.

PMID- 12526973
TI  - Diagnostic accuracy of 13C-urea breath test for Turkish children with
      Helicobacter pylori infection.

PMID- 12526974
TI  - Successful treatment of giant cell hepatitis with Rebetron
      (interferon/ribavirin).

PMID- 12526975
TI  - Two cases of primary biliary cirrhosis complicated with syringomyelia.

PMID- 12526976
TI  - Labeling may be an important cause of reduced quality of life in chronic
      hepatitis C.

PMID- 12526977
TI  - A rare but endocrine cause of chronic diarrhea.

PMID- 12526978
TI  - A new treatment for HCV-ulcerative colitis comorbidity intolerant to INF-alpha.

PMID- 12526979
TI  - Gastric intramural pseudocyst--a complication of percutaneous drainage of an
      acute pancreatic pseudocyst.

PMID- 12526980
TI  - Ischemic colitis associated with paclitaxel and carboplatin chemotherapy.

PMID- 12526981
TI  - Melatonin for ulcerative colitis?

PMID- 12526984
TI  - Immunophilins and their ligands: insights into survival and growth of human
      neurons.
AB  - The immunophilin receptors implicated in generating the neurotrophic effects of
      FK506 and rapamycin (RM) are unknown. Our studies are directed at (1)
      characterizing the effects of FK506 and RM on human fetal neurons and glia (2)
      revealing the role played by the immunophilin FKBP receptors and downstream
      effectors in mediating the effects of FK506 and RM on human brain cells and (3)
      clarifying the role of immunophilins (IP) in the normal and degenerating human
      brain. These studies provide the basis for the implementation of the FDA-approved
      immunophilin ligands (IPL) in the pharmacologic treatment of Parkinson's disease
      (PD). Additionally, they establish a potential link to pathogenetic and repair
      mechanisms associated with neurodegeneration and propose FKBP12 and FKBP52 as
      substrates that can be targeted by future drug design endeavors. Our studies also
      show for the first time that the immunophilin FKBP is present in the human brain
      and that its levels are altered in the brain of patients with neurodegenerative
      diseases. The increased levels of FKBP12 in neurons situated in areas of
      degeneration suggest that it may become a novel marker of pathology. Although the
      precise role of this immunophilin in the normal and degenerating brain awaits
      further clarification, this study suggests that FKBP might play a role in
      neuroprotection against abnormal protein aggregation, as well as participate in
      axonal transport and synaptic vesicle assembly. The rotamase activity of FKBP is
      likely to underlie these functions. If this hypothesis is confirmed, therapeutic
      attempts using rotamase activity-inhibiting immunophilin ligand administration in
      neurodegenerative disease patients need to be carefully designed.

PMID- 12526985
TI  - Neural substrates linking balance control and anxiety.
AB  - This communication provides an update of our understanding of the neurological
      bases for the close association between balance control and anxiety. New data
      suggest that a vestibulo-recipient region of the parabrachial nucleus (PBN)
      contains cells that respond to body rotation and position relative to gravity.
      The PBN, with its reciprocal relationships with the extended central amygdaloid
      nucleus, infralimbic cortex, and hypothalamus, appears to be an important node in
      a primary network that processes convergent vestibular, somatic, and visceral
      information processing to mediate avoidance conditioning, anxiety, and
      conditioned fear responses. Noradrenergic and serotonergic projections to the
      vestibular nuclei also have parallel connections with anxiety pathways. The
      coeruleo-vestibular pathway originates in caudal locus coeruleus (LC) and
      provides regionally specialized noradrenergic input to the vestibular nuclei,
      which likely mediate effects of alerting and vigilance on the sensitivity of
      vestibulo-motor circuits. Both serotonergic and nonserotonergic pathways from the
      dorsal raphe nucleus and the nucleus raphe obscurus also project differentially
      to the vestibular nuclei, and 5-HT(2A) receptors are expressed in amygdaloid and
      cortical targets of the PBN. It is proposed that the dorsal raphe nucleus pathway
      contributes to both (a) a tradeoff between motor and sensory (information
      gathering) aspects of responses to self-motion and (b) a calibration of the
      sensitivity of affective responses to aversive aspects of motion. This updated
      neurologic model continues to be a synthetic schema for investigating the
      neurological and neurochemical bases for comorbidity of balance disorders and
      anxiety disorders.

PMID- 12526986
TI  - The anterior cingulate as a conflict monitor: fMRI and ERP studies.
AB  - We propose that the anterior cingulate cortex (ACC) contributes to cognition by
      detecting the presence of conflict during information processing, and to alert
      systems involved in top-down control to resolve this conflict. Here, we review
      several functional magnetic resonance imaging (fMRI) and event-related potential
      (ERP) studies that have used simple response interference tasks, and propose that
      ACC activity is activated prior to the response during correct conflict trials
      and reflected in the frontocentral N2, and immediately following error trials and
      reflected in the error-related negativity (ERN). Furthermore, we suggest that
      certain disturbances in cognition and behavior in common mental disorders such as
      schizophrenia and obsessive-compulsive disorder (OCD) can be understood as
      resulting from alteration in performance monitoring functions associated with
      this region of the brain.

PMID- 12526987
TI  - Targeted gene delivery to the nervous system using herpes simplex virus vectors.
AB  - Neurotrophic factors are highly potent macromolecules with protean effects.
      Although they are highly effective in vitro and in animal models in vivo, they
      have not been successfully applied to the treatment of human disease. Our
      laboratories have developed recombinant herpes simplex virus (HSV)-based vectors,
      that we have demonstrated may be used to deliver and express neurotrophic factor
      genes in dorsal root ganglion neurons to protect against the development of
      neuropathy in animal models, without causing systemic side effects. In a similar
      fashion, we have demonstrated that a vector expressing proenkephalin to mediate
      the release of opioid peptides from afferent nerve terminals in the spinal cord
      can be used to produce a localized antinociceptive effect in animal models of
      pain. Targeted gene delivery using HSV-based vectors offers a means to utilize
      short-lived peptides to produce specific effects in the nervous system.

PMID- 12526988
TI  - Regulation of conditioned responses of basolateral amygdala neurons.
AB  - The basolateral amygdala (BLA) is a component of a system that drives and
      modulates affective behavior. Some forms of affective behavior are regulated by
      the prefrontal cortex (PFC) and enhanced by dopamine (DA). By using intracellular
      and extracellular electrophysiological techniques in anesthetized rats, our
      studies attempt to uncover cellular mechanisms that allow for regulation of
      affect by PFC-induced inhibition of BLA output and plasticity, as well as
      mechanisms by which DA enhances affective behavior via modulation of BLA neuronal
      excitability, afferent input and plasticity. We have found that stimulation of
      medial PFC (mPFC) results in a profound inhibition of BLA output, manifest as a
      suppression of spontaneous, intracellular current-driven or sensory cortical
      afferent-driven spike firing of BLA projection neurons. This inhibition is
      mediated by excitation of GABAergic interneurons of the BLA. Activation of DA
      receptors attenuates this inhibitory action of the mPFC, while enhancing other
      (i.e., sensory-related) inputs by increases in postsynaptic excitability of BLA
      projection neurons. Furthermore, Pavlovian conditioning procedures that pair an
      odor with a footshock result in enhanced odor-evoked postsynaptic potentials.
      This plasticity of odor-evoked responses is blocked by antagonism of DA receptors
      and by stimulation of mPFC. Our data indicate that the mPFC exerts regulatory
      control over BLA via suppression of spontaneous and sensory-driven activity, as
      well as BLA plasticity. Activation of DA receptors suppresses the inhibitory
      influence of the mPFC, allowing sensory-driven BLA activity and plasticity.
      Functionally, in the presence of high DA levels, which suppresses mPFC-evoked
      inhibition, one source of affective control will be dampened. Furthermore,
      sensory-related inputs will be further enhanced by the increased excitability of
      BLA neurons. This situation is expected to maximize affective responses to
      sensory stimuli, as well as plasticity.

PMID- 12526989
TI  - Integrated approaches to the action of general anesthetics and alcohol.
AB  - The use of inhalational anesthetics was first publicly demonstrated in 1846.
      Alcohol has been consumed for centuries and is now our most costly drug abuse
      problem. Despite widespread use, the molecular mechanism of action of these drugs
      has remained an enigma. The prevailing theory suggests that alcohol and
      anesthetics interact directly with neuronal membrane proteins to cause their
      effects. Our laboratories are using a variety of cutting edge approaches to gain
      insight into the mechanism of action of these drugs. Biophysical approaches such
      as high-resolution nuclear magnetic resonance (NMR) spectroscopy and genetic
      engineering approaches such as creation of designer mice are currently being used
      by our laboratories. These approaches are providing exciting insight into how
      these drugs exert their effects. This research could ultimately result in safer
      and better anesthetics, may lead to treatments for alcoholism, and may provide
      insight into basic biologic processes such as consciousness.

PMID- 12526990
TI  - Impaired prefrontal inhibition in schizophrenia: relevance for cognitive
      dysfunction.
AB  - In schizophrenia, critical deficits in cognitive functions appear to reflect
      altered neural processing in the prefrontal cortex (PFC). Given the essential
      role of inhibitory neurotransmission in mediating these cognitive functions, we
      sought to determine whether abnormalities in the inhibitory circuitry of the PFC
      may contribute to the cognitive deficits of schizophrenia. In situ hybridization
      analyses in postmortem brain tissue from subjects with schizophrenia revealed
      that a subset of GABA neurons in PFC layers 1-5 do not express detectable levels
      of the mRNAs encoding glutamate decarboxylase (GAD(67)), a synthesizing enzyme
      for GABA, or the GABA membrane transporter (GAT-1), which is responsible for the
      reuptake of GABA into the nerve terminal. Furthermore, the affected GABA neurons
      appear to include chandelier cells, since decreased expression of GAT-1 mRNA is
      associated with decreased GAT-1 protein immunoreactivity in chandelier neuron
      axon terminals. Finally, immunocytochemical studies revealed that decreased GAT-1
      immunoreactivity in chandelier neuron axon terminals is associated with an
      increase in a marker of GABA(A) receptors at the postsynaptic targets of
      chandelier neuron axons, the axon initial segment (AIS) of pyramidal neurons.
      These findings suggest that schizophrenia is associated with an up-regulation of
      GABA(A) receptors at pyramidal neuron AIS in response to deficient GABAergic
      input from chandelier neurons. Selective disruptions in inhibitory
      neurotransmission are likely to distort aspects of pyramidal neuron function
      important for working memory tasks, and thus may contribute to cognitive
      dysfunction in schizophrenia.

PMID- 12526991
TI  - Presynaptic calcium influx, neurotransmitter release, and neuromuscular disease.
AB  - The synapse between a spinal motor neuron and a muscle cell is normally very
      effective at eliciting muscle contraction. A reliable connection between these
      two cells occurs because a single action potential reaching the motor nerve
      terminal normally releases hundreds of packets of transmitter containing
      thousands of chemical transmitter molecules, which cross the synapse and
      encounter a specialized region of postsynaptic muscle. Within the muscle membrane
      are thousands of receptor proteins specific for this transmitter. Activation of
      these postsynaptic receptors allows positively charged ions to cross the muscle
      membrane, generating a muscle cell action potential that leads to muscle
      contraction. Because of its size, contraction of a muscle cell requires the
      activation of an exceptionally large number of neurotransmitter receptors. To
      understand the regulation of this reliable communication and to elucidate details
      of pathological conditions that lead to muscle weakness, we have studied the
      subcellular mechanisms that govern synaptic transmission at the neuromuscular
      junction (NMJ). This article will review recent electron microscopic,
      electrophysiological, and imaging data in a discussion of the function of the
      motor nerve terminal in both normal and diseased states. Taken together, the
      existing data lead us to hypothesize that a small fraction of available calcium
      channels open within the transmitter releasing regions of the NMJ and that each
      vesicle fusion event is triggered by calcium flux through a single channel
      opening.

PMID- 12526992
TI  - Selective prefrontal cortex inputs to dopamine cells: implications for
      schizophrenia.
AB  - Dopamine (DA) neurons in the substantia nigra (SN) and ventral tegmental area
      (VTA) form several projection systems with diverse functions, such as motor
      planning through the striatum, reward seeking via the nucleus accumbens (NAc),
      and cognitive control through the prefrontal cortex (PFC). Disruptions in DA cell
      activity profoundly impair these functions and contribute to serious clinical
      conditions such as Parkinson's disease and schizophrenia. DA neurons have been
      extensively investigated in studies detailing their anatomy, physiology, and
      neurochemical regulation. Moreoever, recordings from behaving animals suggest
      that phasic changes in DA cell firing signal expectancy or attentional shifts
      associated with approach/avoidance behavior. These ideas raise interesting
      questions regarding how DA neurons are regulated to produce such phasic signals.
      For example, it is not yet known how different classes of DA projection neurons
      are regulated by specific inputs. In the first study of its kind within the VTA,
      our laboratory recently demonstrated that excitatory inputs from the PFC synapse
      selectively onto DA neurons that project back to the PFC but not onto DA cells
      that project to the NAc. These findings may explain some of the unique functional
      properties of mesoprefrontal DA neurons. Moreover, the results are important for
      understanding the pathophysiology of mental disorders such as schizophrenia.

PMID- 12526993
TI  - Intrastriatal grafting of glomus cells ameliorates behavioral defects of
      Parkinsonian rats.
AB  - Parkinson's disease is associated with severe motor dysfunctions due to a
      progressive loss of dopaminergic neurons in substantia nigra. Transplantation of
      midbrain neurons from human fetuses to the striatum of patients provides
      effective treatment for the disease. This type of approach, however, could not be
      adopted widely due to insufficient supply of fetal materials and the
      controversial ethical and legal issues. The carotid body is a chemoreceptive
      organ containing chromaffin-like glomus cells that secrete dopamine (DA) as the
      neurotransmitter. Here, we report the generation of a clonal dopaminergic cell
      line of the carotid body using the H-2K(b)-tsA58 transgenic mouse. Cells from the
      carotid body were immortalized at the permissive temperatures and in the presence
      of gamma-interferon. The glomus cells were isolated by flow cytometry, and
      purified to homogeneity by a limited dilution procedure. Upon switching the
      culture to a nonpermissive condition, the immortal cells ceased to divide, became
      terminally differentiated and secreted high levels of DA. In rats rendered hemi
      Parkinsonian by injection of 6-hydroxydopamine (6-OHDA) into the substantial
      nigra, intrastriatal grafting of the glomus cells resulted in significant
      recovery of motor asymmetries and sensorimotor dysfunction. The effects were
      apparent approximately 10 days after transplantation and remained throughout the
      4 months of the study. The recovery of behavioral defects was correlated with the
      ability of cell grafts to release DA in the brain. As none of the existing
      treatments for Parkinson's disease is completely satisfactory, establishment of a
      clonal cell line that secretes DA opens a new avenue for the effective control of
      this neurological disorder.

PMID- 12526994
TI  - Stress-induced Parkinson's disease: a working hypothesis.
AB  - Some cases of Parkinson's disease (PD) can be attributed to genetic mutations,
      others to specific environmental factors; yet the cause of a great majority of
      cases is unknown. Physical and emotional traumas were once briefly considered as
      factors in the pathophysiology of this disorder. With increasing evidence that
      stress can indeed increase neuronal loss in some brain regions, this hypothesis
      deserves to be reexamined. Stress increases the extracellular availability of
      glucocorticoids (GCs), dopamine (DA), and glutamate in the striatum as well as
      other brain regions. These factors undoubtedly can serve to enhance the functions
      of the striatum. However, each also has the capacity to be neurotoxic. Moreover,
      they can act synergistically to promote neuronal loss. Thus, we propose that
      stress might, indeed, be a key factor in the loss of DA neurons that underlies
      PD.

PMID- 12526995
TI  - Protein kinases and light: unlikely partners in a receptor localization puzzle.
AB  - Brief flashes of light directed at neuronal cell bodies and proximal dendrites of
      neurons in culture can enhance whole-cell electrophysiological responses mediated
      by NMDA and GABA(A) receptors. In experiments aimed at identifying the molecular
      moieties responsible for mediating this phenomenon, we observed that broad
      spectrum protein kinase inhibitors substantially amplified the actions of light.
      Kinase inhibitors, however, were surprisingly ineffective in altering light
      induced potentiation of recombinant NMDA receptors expressed in Chinese hamster
      ovary (CHO) cells. Furthermore, receptors assembled from truncated NMDA receptor
      subunits, previously shown to be relatively insensitive to modulation via
      phosphorylation, remained light sensitive. Phosphatase inhibitors had no effects
      of light-induced NMDA receptor potentiation in neurons, and nucleated patches
      excised from neuronal somata behaved similarly to CHO cells. Taken together,
      these data suggests that the effects of kinase inhibitors were unrelated to the
      molecular mechanism of light-induced potentiation. We propose a model whereby
      kinase inhibition promotes an enrichment of NMDA receptors in the neuronal cell
      body vs. the distal dendrites. Under these conditions, NMDA receptor
      redistribution elicited by kinase inhibitors would increase the number of
      receptors exposed to light and, as a consequence, the whole cell response. These
      observations support a critical role for protein kinases in the rapid
      redistribution of neurotransmitter receptors, with profound physiological
      significance.

PMID- 12526996
TI  - Dopamine modulation of neuronal function in the monkey prefrontal cortex.
AB  - We developed a brain slice preparation that allowed us to apply whole-cell
      recordings to examine the electrophysiological properties of identified synapses,
      neurons, and local circuits in the dorsolateral prefrontal cortex (DLPFC) of
      macaque monkeys. In this article, we summarize the results from some of our
      recent and current in vitro studies in the DLPFC with special emphasis on the
      modulatory effects of dopamine (DA) receptor activation on pyramidal and
      nonpyramidal cell function in superficial layers in DLPFC areas 46 and 9.

PMID- 12526997
TI  - Differential plasticity in neocortical networks.
AB  - Understanding the synaptic and molecular basis for learning and memory in the
      neocortex depends upon a clear understanding of the anatomical and connectional
      diversity within this structure. To the extent that different types of synapses
      within the neocortex have distinct electrophysiological and, thus, molecular
      properties, the types of plasticity that these synapses manifest may also be
      distinct. If thresholds for plasticity are different for excitatory synapses onto
      inhibitory neurons than for excitatory synapses onto excitatory neurons, the same
      pattern of excitatory presynaptic activity will have difference consequences on
      excitatory and inhibitory networks. Differential plasticity will thus affect the
      way in which experience can modify sensory maps in the neocortex. Experimental
      support for this hypothesis is presented, as well as some predictions about the
      function of different types of neocortical pathways and plasticity.

PMID- 12526998
TI  - Temporal asymmetry in spike timing-dependent synaptic plasticity.
AB  - Activity-dependent synaptic modification is critical for the development and
      function of the nervous system. Recent experimental discoveries suggest that both
      the extent and the direction of modification may depend on the precise timing of
      pre- and postsynaptic action potentials (spikes). This phenomenon, termed spike
      timing-dependent plasticity (STDP), provides a new, quantitative interpretation
      of Hebb's rule and raises intriguing questions regarding the fundamental
      processes of cellular signaling. In this article, we summarize previous results
      obtained in a hippocampal culture system, where an asymmetric window of spike
      timing was found for paired pre- and postsynaptic spiking to induce STDP. We also
      discuss our recent studies using a "triplet-spiking" paradigm that reveals
      nonlinear, temporally asymmetric integration of STDP.

PMID- 12526999
TI  - Pseudorabies virus-induced expression of nitric oxide synthase isoforms.
AB  - In addition to its role as a neurotransmitter, studies have postulated both
      neuroprotective and neurotoxic roles for nitric oxide (NO) generated in response
      to infections with neurotropic viruses. This study examined the expression of
      neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS)
      isoforms of NOS induced by neuronal infection with virulent and attenuated
      strains of pseudorabies virus (PRV). Caudal brainstem neurons infected by
      peripheral inoculation of the viscera served as the model system. Neuronal
      infection induced the expression of nNOS and iNOS, but the timing and the
      apparent magnitude of NOS expression varied according to the virulence of the
      infecting strain of virus. Expression of nNOS was observed in infected neurons
      that did not express this enzyme in control animals, and the onset of expression
      was earlier in animals infected with virulent PRV. Expression of iNOS was largely
      restricted to monocytes and macrophages that invaded the brain in response to PRV
      infection. These iNOS-expressing cells were observed earlier in animals infected
      with the virulent virus, and were differentially concentrated in areas exhibiting
      virus-induced neuropathology. Collectively, these data suggest functionally
      diverse roles for NO in the brain response to PRV neuronal infection.

PMID- 12527000
TI  - In vitro interaction of the glycine receptor with the leptin receptor.
AB  - The coordination and regulation of electrical signals across excitable cells is a
      complex, dynamic phenomenon requiring, in part, the interaction of ion channels
      with cellular constituents. The intracellular loops or domains of many ion
      channel subunits have been shown to specifically bind other cellular components
      that act in receptor targeting, localization, regulation, or modulation of
      function. In this report we describe experiments in which the large intracellular
      loop of the alpha1 subunit of the glycine receptor (GlyR) was used as "bait" to
      search a human brain library for proteins that may interact with this receptor.
      The GlyR is the major inhibitory ligand-gated ion channel in the spinal cord and
      lower brainstem, and is a member of the nicotinicoid superfamily of receptors.
      These in vitro studies identified the leptin receptor as a potential binding
      partner for GlyR, and this interaction was confirmed in binding studies that used
      the cytoplasmic loop of the GlyR as an affinity ligand for homogenized tissue
      from rat spinal cords and lower brainstem. Mass spectrometric analyses of eluants
      showed that the leptin receptor was specifically extracted from the homogenized
      and solubilized tissue. The long form of the leptin receptor is expressed in the
      hypothalamus (as is the GlyR) and among its other functions, it quickly evokes a
      satiation response upon binding leptin. Our in vitro results suggest that this
      rapid initial response may be mediated through direct interaction of the leptin
      receptor with GlyR or a related nicotinicoid family member homolog.

PMID- 12527001
TI  - The role of the ETS gene PEA3 in the development of motor and sensory neurons.
AB  - The ETS family of transcription factors includes two members, ER81 and PEA3,
      which are expressed in groups of sensory and motor neurons supplying individual
      muscles. To investigate a possible role of these genes in determining sensory
      and/or motor neuron phenotype, we studied mice in which each of these genes was
      deleted. In contrast to the deletion of ER81, which blocks the formation of
      projections from muscle sensory neurons to motor neurons in the spinal cord,
      deletion of PEA3 causes no obvious effects on sensory neurons or on their
      synaptic connections with motor neurons. PEA3 does play a major role in the
      formation of some brachial motoneurons however. Motoneurons innervating the
      cutaneous maximus muscle, which are normally PEA3(+), fail to develop normally so
      that postnatally the muscle is innervated by few motoneurons and is severely
      atrophic. Other studies suggest that these motoneurons initially appear during
      development but fail to contact their normal muscle targets.

PMID- 12527002
TI  - Channel gating of NMDA receptors.
AB  - Glutamate receptors specifically activated by N-methyl-D-aspartate (NMDA
      receptors) are ion channels that play multiple fundamental roles in the
      physiology of vertebrate nervous systems. The mechanisms that control the opening
      and closing, or gating, of the channel of NMDA receptors are among the most basic
      determinants of receptor function, and yet are not well understood. Here we
      consider current understanding of the link between agonist binding and NMDA
      receptor channel gating, of the conformational changes that occur during gating,
      and of the location of the channel gate. Information is drawn from studies of
      NMDA receptors themselves, of other types of glutamate receptors, and of more
      distantly related potassium channels.

PMID- 12527003
TI  - Excitatory action of an immature glycinergic/GABAergic sound localization
      pathway.
AB  - Most mammals determine the azimuthal direction of incoming sound using auditory
      cues arising from differences in interaural sound intensity. The first station in
      the ascending auditory pathway, which processes interaural intensity differences,
      is the lateral superior olive (LSO), a binaural nucleus in the auditory
      brainstem. LSO neurons encode interaural intensity differences by integrating
      excitatory input from the ipsilateral cochlea and inhibitory input from the
      contralateral cochlea. Both inputs converge on single neurons in a highly
      organized, frequency-specific manner. The correct development of the precise
      arrangement of these inputs and their physiological properties depends on
      neuronal activity. Previous studies have shown that inhibitory,
      glycinergic/GABAergic inputs to the LSO are transiently depolarizing, and it has
      been hypothesized that this depolarizing action enables developing inhibitory
      inputs to act as excitatory inputs. In support of this hypothesis, we recently
      demonstrated that depolarizing glycinergic/GABAergic inputs can increase the
      intracellular calcium concentration in immature LSO neurons and elicit action
      potentials. These results provide support for the notion that the influence of
      glycinergic/GABAergic synaptic activity on development of the LSO involves
      calcium-dependent signaling mechanisms.

PMID- 12527004
TI  - Comprehensive phenotyping of sensory neurons using an ex vivo somatosensory
      system.
AB  - In adults, primary sensory neurons exhibit pronounced diversity in many
      phenotypic traits including peripheral response properties, somal spike shape,
      neurochemical content, and laminar distribution of projections in the spinal
      dorsal horn. While these traits are correlated with sensory submodality type,
      single traits are not sufficient to accurately characterize individual neurons.
      We have recently developed a novel mouse ex vivo somatosensory preparation that
      allows the examination of multiple traits for individual cutaneous sensory
      neurons. Here we describe the results from our initial studies of adult and
      neonatal mice employing this preparation. Adult mice were anesthetized and
      perfused with chilled oxygenated artificial cerebrospinal fluid (aCSF). The
      spinal cord, dorsal root ganglia (DRGs), several attached dorsal cutaneous nerves
      (DCNs), and skin were isolated and placed in a chamber with a circulating bath of
      oxygenated aCSF. Sensory neuron somata were impaled, their cutaneous mechanical
      response properties were determined, and then one soma/ganglion was injected with
      Neurobiotin (NB). Spinal cord sections containing the cell's central projections
      were reacted with horseradish peroxidase-conjugated avidin and visualized using
      diaminobenzidene. DRG sections were reacted with primary antisera for calcitonin
      gene-related peptide (CGRP), and the NB-stained somata were visualized using
      avidin-FITC. In these initial studies, neonatal cutaneous sensory neurons are
      found to be virtually miniature replicas of the their adult counterparts. These
      findings challenge long-held beliefs that the laminar distribution of the central
      projections and somal spike properties of cutaneous low-threshold
      mechanoreceptors (LTMRs) undergo delayed maturation during the first 2-3 weeks of
      postnatal development.

PMID- 12527005
TI  - Loss of the tailless gene affects forebrain development and emotional behavior.
AB  - We are studying the role of the evolutionarily conserved tlx gene in forebrain
      development in mice. Tlx is expressed in the ventricular zone that gives rise to
      neurons and glia of the forebrain. We have shown by mutating the tlx gene in
      mice, that in the absence of this transcription factor, mutant animals survive,
      but suffer specific anatomical defects in the limbic system. Because of these
      developmentally induced structural changes, mice with a mutation in the tlx gene
      can function, but exhibit extreme behavioral pathology. Mice show heightened
      aggressiveness, excitability, and poor cognition. In this article, we present a
      summary of our findings on the cellular and behavioral changes in the forebrain
      of mutant animals. We show that absence of the tlx gene leads to abnormal
      proliferation and differentiation of progenitor cells (PCs) in the forebrain from
      embryonic day 9 (E9). These abnormalities lead to hypoplasia of superficial
      cortical layers and subsets of GABAergic interneurons in the neocortex. We
      examined the behavior of mutant animals in three tests for anxiety/fear: the open
      field, the elevated plus maze, and fear conditioning. Mutant animals are less
      anxious and less fearful when assessed in the elevated plus and open-field
      paradigm. In addition, mutant animals do not condition to either the tone or the
      context in the fear-conditioning paradigm. These animals, therefore, provide a
      genetic tool to delineate structure/function relationships in defined regions of
      the brain and decipher how their disruption leads to behavioral abnormalities.

PMID- 12527006
TI  - Hippocampal memory and plasticity in superoxide dismutase mutant mice.
AB  - The reactive oxygen species (ROS) superoxide is well known for its role in
      disease mechanisms. Mounting evidence indicates, however, that superoxide also is
      generated for useful purposes and contributes to normal physiologic function.
      Studies with transgenic mice that overexpress superoxide scavengers show that
      certain types of memory function and underlying neuronal processes are impaired
      under conditions of severely reduced superoxide signaling. These findings have
      implications for the use of antioxidant treatments as well as for our
      understanding of the signaling events involved in cognition.

PMID- 12527007
TI  - Lateral inhibition in the olfactory bulb and in olfaction.
AB  - Lateral inhibition in the olfactory bulb is mediated by circuits that involve
      reciprocal dendrodendritic connections between mitral and granule cells. Because
      of the properties of these connections and also because odor stimuli are not
      represented in an obviously topographic fashion, questions have been raised about
      whether the function of local inhibition in the olfactory bulb can be compared to
      the function of inhibition in other brain areas. Here, I propose an analysis of
      local inhibition in the olfactory bulb based on the simplification that olfactory
      bulb circuitry can be thought of as implementing a simple linear two-dimensional
      filter. This analysis highlights some important characteristics of the circuitry
      of the olfactory bulb and suggests that the function of lateral inhibition in the
      olfactory bulb may be to compensate for generalized, spatially distributed
      activation that otherwise may obscure the specific, discrete patterns of
      glomerular activation seen across the olfactory bulb.

PMID- 12527008
TI  - Oculographic analysis of word reading in hemispatial neglect.
AB  - Neglect dyslexia is a disorder in which individuals misread text appearing on the
      contralateral side of space following an acquired lesion, usually to the right
      parietal lobe. This disorder is generally attributed to an impairment in
      representing spatial information. To determine whether the spatial
      representations underlying reading differ from those mediating other forms of
      visual behavior, we investigated the co-occurrence of neglect dyslexia with that
      of neglect, which manifests on tasks such as line bisection or line cancellation.
      We also examined the correlation between neglect dyslexia, when present, and eye
      movements in order to characterize the neglect dyslexia disorder further. Whereas
      there is no clear relationship between the reading disorder and other symptoms of
      visuospatial neglect, suggesting segregated spatial representations, there is a
      direct correspondence between the oculomotor performance of patients with neglect
      dyslexia and their reading behavior. This latter result suggests that the reading
      deficit may well arise from the failure to register and perceive the
      contralesional information.

PMID- 12527009
TI  - Spatial working memory in human extrastriate cortex.
AB  - The performance of spatial working memory tasks is known to evoke activity in a
      set of higher-order association areas, including the prefrontal cortex, posterior
      parietal cortex and the frontal and supplementary eye fields. Recent
      physiological studies in monkey have shown that memory-related activity also is
      found in extrastriate cortex [J. Neurophysiol. 84 (2000) 677]. We conducted
      functional magnetic resonance imaging studies to determine whether human
      extrastriate cortex contributes to the on-line maintenance of spatial information
      in an eye movement task. We found that performance of memory-guided saccades, as
      compared to visually guided saccades, elicited significant activation in two
      areas of extrastriate cortex: the posterior superior temporal sulcus (PST) and
      lateral occipitotemporal cortex (LOT). Both areas also were activated during the
      basic sensorimotor task of visually guided saccades as compared to fixation. We
      further determined that area LOT is close to but distinct from motion-sensitive
      area MT+. These findings demonstrate that areas PST and LOT, along with higher
      level association cortex, help to encode and maintain spatial representations.

PMID- 12527010
TI  - Modeling neural oscillations.
AB  - A brief review of oscillatory activity in neurons and networks is given.
      Conditions required for neural oscillations are provided. Three mathematical
      methods for studying the coupling between neural oscillators are described: (i)
      weak coupling, (ii) firing time maps, and (iii) leaky integrate-and-fire methods.
      Several applications from macroscopic motor behavior to slice phenomena are
      provided.

PMID- 12527011
TI  - Functional heterogeneity within Broca's area during verbal working memory.
AB  - In previous fMRI research, we found that two subregions of the left inferior
      frontal cortex showed distinct patterns of activity during a verbal working
      memory task. Specifically, a more dorsal region tracked with performance, while a
      more ventral region was sensitive to lexical status. To test the veracity of this
      finding, we developed a new method for meta-analysis of neuroimaging results. In
      this method, Gaussian probability distributions are formed around stereotaxic
      coordinates obtained from published neuroimaging studies. These probability
      distributions are then combined to identify regions of convergence across
      studies. When this method was applied to prior studies of working memory, the
      results largely paralleled those from earlier reviews of the literature on
      working memory, but also confirmed our empirical findings showing distinct foci
      within Broca's area. Further application of this meta-analytic technique
      substantiated the dissociation in these regions for performance and sublexical
      processing. These results help to validate a novel approach for meta-analysis of
      neuroimaging findings that avoids many of the subjective assumptions involved in
      alternative approaches.

PMID- 12527012
TI  - Mapping cortical columnar structures using fMRI.
AB  - Mapping cortical columnar structures is important to understand cortical
      information processing. To map submillimeter columnar structures noninvasively,
      we have evaluated various functional magnetic resonance imaging (fMRI) techniques
      using a well-established feline orientation column model. The conventional
      positive blood oxygenation level-dependent (BOLD) signal is widespread and
      diffuse due to large venous vessel contributions, resulting in its poor
      specificity to columns. However, the early-negative BOLD signal is induced by the
      early oxygen consumption increase without significant change in blood flow. This
      negative signal has been successfully applied for columnar mapping. Tissue
      specific cerebral blood flow (CBF) response is also specific to individual
      cortical columns, suggesting that parenchyma-specific fMRI techniques are capable
      to map individual single-condition functional cortical columns in animals as well
      as humans.

PMID- 12527013
TI  - Top-down influence in early visual processing: a Bayesian perspective.
AB  - Traditional views of visual processing suggest that early visual neurons are
      static spatiotemporal filters that extract local features by feedforward
      computation. The extracted information is then fed forward through a chain of
      modules to successively higher visual areas for further analysis. Recording from
      early visual neurons in awake behaving monkeys, we revealed there are many levels
      of complexity in the information processing of the early visual cortex. We found
      that the early visual neurons not only are sensitive to features within their
      receptive fields (RFs) but also to the global context of a visual scene, the
      behavioral relevance of the stimuli and the experience of the animals. These
      findings suggest that the early visual cortex (V1 and V2) is tightly coupled to
      and highly interactive with the rest of the visual system. The top-down
      interaction, mediated by recurrent feedback connections, introduces contextual
      information to influence the perceptual inference in the early visual cortex.

PMID- 12527014
TI  - The tolerance for visual feedback distortions in a virtual environment.
AB  - We are interested in using a virtual environment with a robotic device to extend
      the strength and mobility of people recovering from strokes by steering them
      beyond what they had thought they were capable of doing. Previously, we
      identified just noticeable differences (JND) of a finger's force production and
      position displacement in a virtual environment. In this paper, we extend this
      investigation by identifying peoples' tolerance for distortions of visual
      representations of force production and positional displacement in a virtual
      environment. We determined that subjects are not capable of reliably detecting
      inaccuracies in visual representation until there is 36% distortion. This
      discrepancy between actual and perceived movements is significantly larger than
      the JNDs reported in the past, indicating that a virtual robotic environment
      could be a valuable tool for steering actual movements further away from
      perceived movements. We believe this distorted condition may allow people
      recovering from strokes, even those who have perceptual or cognitive deficits, to
      rehabilitate with greater ease.

PMID- 12527015
TI  - Teaching the /r/-/l/ discrimination to Japanese adults: behavioral and neural
      aspects.
AB  - Several studies have been conducted to address the learning of a nonnative speech
      contrast in adulthood, using native speakers of Japanese and the English /r/-/l/
      contrast. Japanese adults were asked to identify contrasting /r/-/l/ stimuli
      (e.g., "rock-lock"). An adaptive training regime starting with initially easy
      stimuli was contrasted with a fixed training regime using difficult stimuli, with
      some subjects receiving feedback on the correctness of their responses and others
      receiving no feedback in both conditions. After three and six sessions of
      training, subjects received tests assessing identification and discrimination of
      /r/-/l/ stimuli as well as generalization. In all cases except fixed training
      without feedback, subjects showed clear evidence of learning, and several
      indicators suggested that training affects speech perception, rather than simply
      auditory processes. Neuroimaging studies currently underway are examining the
      neural basis of these findings.

PMID- 12527016
TI  - Neuronal activity related to rule and conflict in macaque supplementary eye
      field.
AB  - Neuronal activity in macaque supplementary eye field (SEF) is enhanced during
      performance of the antisaccade task. This could be related to the selection of
      targets by a difficult rule (move to a location diametrically opposite the cue)
      or to conflict between the automatic tendency to look at the cue and the
      voluntary intention to look away. To distinguish between rule- and conflict-based
      mechanisms of enhancement, we monitored neuronal activity in the SEF during
      performance of a delayed response task in which monkeys selected saccade targets
      in response to peripheral visual cues. In spatial trials, the monkey had to
      select as target the location marked by the cue. In color trials, the monkey had
      to select as target the location associated with the color of the cue. 'Color
      congruent' trials resembled spatial trials in that saccades were directed to the
      location occupied by the cue. Nevertheless, many SEF neurons were sensitive to
      the rule being used, with the majority firing more strongly under the color-rule
      condition. 'Color-incongruent' trials resembled 'color-congruent' trials in that
      a color rule guided target selection. Nevertheless, many SEF neurons were
      sensitive to the spatial relation between cue and saccade, with the majority
      firing more strongly on trials in which they were incongruent. We conclude that
      neuronal activity in the SEF is enhanced in connection both with the use of a
      more difficult rule and with conflict.

PMID- 12527017
TI  - Texture discrimination and unit recordings in the rat whisker/barrel system.
AB  - We have developed a semi-automated technique for acquiring neurophysiological
      data during whisker-based tactile discriminative behavior. Water-deprived,
      blindfolded rats are tethered by means of a harness vest that permits them to
      contact a rough (250 micrometer grooves) or smooth discriminandum with only their
      vibrissae. Discriminanda are mounted on a motor-driven carousel, and the rat
      indicates its choice (rough, smooth) by licking either a right or left water port
      located near the carousel. A narrow light beam detects general proximity of the
      animal's nose to the discriminandum, although actual whisker contact is monitored
      by a SuperVHS camera and measured offline using field-by-field videographic
      analysis. Rats can be trained within 3-6 weeks at which time they perform 100-150
      trials/day at a level of 80% correct. Unit recording from the somatosensory
      cortex reveals that neurons increase their firing upon whisker contact of a
      discriminandum and that firing remains elevated during several hundred
      milliseconds of ongoing contact, even with the smooth surface. Nevertheless,
      despite the animal's ability to distinguish the rough and smooth surfaces,
      overall neuronal firing rates were indistinguishable for the two surfaces. In
      some cases, temporal firing patterns differed, although not in a consistent way
      across recording sites.

PMID- 12527018
TI  - Motor areas in the frontal lobe of the primate.
AB  - There has been a substantial change in our concepts about the cortical motor
      areas. It is now clear that the frontal lobe of primates contains at least six
      premotor areas that project directly to the primary motor cortex (M1). Two
      premotor areas, the ventral premotor area (PMv) and the dorsal premotor area
      (PMd), are located on the lateral surface of the hemisphere. Four premotor areas
      are located on the medial wall of the hemisphere and include the supplementary
      motor area (SMA) and three cingulate motor areas. Each of these premotor areas
      has substantial direct projections to the spinal cord. Corticospinal axons from
      the premotor areas terminate in the intermediate zone of the spinal cord, and
      some also terminate in the ventral horn around motoneurons. In this respect, the
      premotor areas are like M1 and appear to have direct connections with spinal
      motoneurons, particularly those innervating hand muscles. Furthermore, it is
      possible to evoke movements of the distal and proximal forelimb using
      intracortical stimulation at relatively low currents in the premotor areas. Thus,
      the premotor areas appear to have the potential to influence the control of
      movement not only at the level of M1, but also more directly at the level of the
      spinal cord. For these reasons, we have suggested that the premotor areas may
      operate at a hierarchical level comparable to M1. We propose that each premotor
      area is a functionally distinct efferent system that differentially generates
      and/or controls specific aspects of motor behavior.

PMID- 12527019
TI  - Importance of nonpharmacological factors in nicotine self-administration.
AB  - There is mounting evidence that nonpharmacological factors critically modulate
      the effects of several drugs of abuse both in humans and experimental animals.
      This paper reviews research from this laboratory on one factor that influences
      the degree to which nicotine is self-administered: environmental stimuli that
      form the context within which nicotine is taken. The results suggest that the
      direct, pharmacological actions of nicotine are necessary but not sufficient to
      explain either the high rates of self-administration exhibited by laboratory
      animals or cigarette smoking by humans, and that future investigations on the
      neurophysiological effects of nicotine that underlie smoking behavior must take
      into account the environmental context within which the behavior occurs.

PMID- 12527020
TI  - Plasticity of bladder reflex pathways during postnatal development.
AB  - Neuroanatomical and electrophysiological techniques have provided insights into
      the organization of the spinal cord circuitry and the neurotransmitter mechanisms
      involved in primitive voiding reflexes in neonatal animals. Patch clamp studies
      of unitary synaptic transmission in spinal cord slice preparations indicate that
      developmental plasticity in sacral parasympathetic reflex pathways is due in part
      to alterations in the glutamatergic excitatory transmission between interneurons
      and parasympathetic preganglionic neurons. It is proposed that these synaptic
      changes are due to competition between segmental and supraspinal inputs. Thus,
      synaptic remodeling in the sacral parasympathetic nucleus is likely to be an
      important factor in the postnatal maturation of voiding reflexes.

PMID- 12527021
TI  - Vagal function in health and disease: studies in Pittsburgh.
AB  - The integration of behavioral processes with changes in vagally-controlled heart
      rate has been the focus of our investigations. A series of studies is reviewed
      showing that central and peripheral response inhibition is a primary source of
      transient, vagally-induced cardiac slowing during information processing.
      Individual differences in such responses are then shown to relate to the
      amplitude of cardiovascular responses to stressors. Overall, the specificity and
      sensitivity of vagal responses to higher level cortical function is supported by
      our research.

PMID- 12527022
TI  - Psychosocial demands and ambulatory blood pressure: a field assessment approach.
AB  - Ambulatory blood pressure (ABP) has been shown to have independent prognostic
      value, over and beyond the effects of clinic blood pressure (CBP) measures. We
      have examined the role of psychosocial demands in understanding ABP, using an
      electronic diary to measure ongoing experience in the field at the time of each
      blood pressure reading (ecological momentary assessment). In our previous work,
      several psychosocial factors were shown to be associated, within-person, with
      acute fluctuations in ABP in a healthy adult sample. Here, we replicate these
      findings in a new sample, and we also examine associations of the same variables
      with mean ABP (between-person) over a 6-day period. Five measures assumed to be
      markers of psychosocial demands (negative affect, arousal, task demand,
      decisional control, and social conflict) were shown here to be independently
      associated with ABP fluctuations during daily life, after adjustment for posture,
      activity, and substance use. Two of these, measures of task demand and decisional
      control, were also associated with mean ambulatory systolic blood pressure (SBP),
      and these latter associations persisted after controlling for CBP. These results
      support the possibility that psychosocial factors may account for some of the
      unique predictive value associated with ABP, and they support the value of these
      field assessment methods.

PMID- 12527023
TI  - Central nervous system serotonergic responsivity and aggressive disposition in
      men.
AB  - To determine whether normative variability in aggressive behavior correlates
      negatively with central nervous system (CNS) serotonergic function among men,
      plasma prolactin (PRL) responses to a standard fenfluramine challenge
      (administered to assess central serotonergic responsivity) were examined in
      relation to interview-assessed aggression histories among 118 adult males derived
      from a nonpatient, community sample. Fenfluramine-induced, peak PRL rises were
      smaller in subjects whose 'aggression' scores fell above the sample median,
      compared to their less aggressive counterparts (P<.002). Across subjects,
      participants' peak PRL responses likewise covaried inversely with aggression
      history (r(s)=-.32, P<.0005). Additional analyses were conducted on data of 58
      subjects who had also been genotyped for a functional polymorphism in the
      promoter region of the X chromosomal, monoamine oxidase-A (MAO-A) gene. The four
      variants of this repeat polymorphism were grouped for analysis (alleles '1+4' vs.
      '2+3') based on prior report of enhanced transcriptional efficiency in MAO-A
      promoter constructs containing alleles 2 and 3 (repeats of intermediate length).
      Men in the 2/3 allele group had significantly higher aggression scores (P<.05)
      and smaller peak PRL responses to fenfluramine (P<.009) than men in the 1/4
      allele group. When adjusted by analysis of covariance for concomitant variability
      in subjects' PRL responses, aggressive disposition no longer varied significantly
      by genotype. This finding suggests that association of the MAO-A promoter
      polymorphism with this behavioral phenotype may be mediated, in part, by allele
      specific variation in central serotonergic responsivity.

PMID- 12527024
TI  - Stress, immune reactivity and susceptibility to infectious disease.
AB  - Psychological stress is known to affect immune function and to predict infectious
      disease susceptibility. However, not all individuals who are stressed develop
      disease. In the present article, we report on a series of studies from our
      laboratory describing interindividual variability of immune responses to
      psychological stress. In our initial series of experimental investigations, we
      demonstrated that acute laboratory stress alters both quantitative and functional
      components of cellular immunity. An examination of response variability revealed
      that individuals differ substantially in the magnitude of these immune responses.
      These differences were found to parallel (and be predicted by) interindividual
      variability in stress-induced sympathetic nervous system activation. Further
      investigation revealed that individuals vary consistently in the magnitude of
      their immune responses to stress, making it conceivable that individual
      differences in immune reactivity provide a vulnerability factor mediating
      relationships between stress and disease. In support of this possibility, we have
      recently reported initial evidence that individual differences in the magnitude
      of stress-induced reduction of immune function may be of clinical significance,
      being related to an immune response relevant for protection against infection,
      antibody response to hepatitis B vaccination.

PMID- 12527025
TI  - Neuroendocrine mechanisms that delay and initiate puberty in higher primates.
AB  - This paper highlights a series of studies using the male rhesus monkey that has
      led to a model for the control of the onset of puberty in higher primates. The
      model proposes that the timing of puberty in these species is governed by the
      duration of a central brake that, during juvenile development, holds in check the
      hypothalamic network of gonadotropin-releasing hormone (GnRH) neurons, which, in
      the adult, drive the pituitary-gonadal axis. The neurobiology of this
      hypothalamic brake, and the physiological mechanisms that time its application
      and removal, are incompletely understood. Nevertheless, the pubertal resurgence
      of pulsatile GnRH release, which terminates the juvenile phase of primate
      development and triggers the initiation of puberty in man and monkeys, is
      associated with structural and molecular remodeling of the hypothalamus. A major
      component of this developmental plasticity appears to involve neuropeptide Y
      (NPY). NPY inhibits GnRH release, and NPY gene expression in the hypothalamus is
      elevated during juvenile development when GnRH release is restrained. Since the
      changes in hypothalamic function and morphology that trigger primate puberty
      unfold in the absence of gonadal steroid feedback, the possibility is raised
      that, in addition to activating the pituitary-gonadal axis at this stage of
      development, they may also contribute directly to the causation of behaviors and
      affective states that emerge at adolescence.

PMID- 12527026
TI  - Viscerosensory activation of noradrenergic inputs to the amygdala in rats.
AB  - Norepinephrine (NE) acts in the amygdala to regulate processes underlying
      acquisition and expression of emotional learning. The present study investigated
      whether stimulation of gastric vagal sensory afferents activates neurons
      immunoreactive for the NE synthetic enzyme, dopamine beta hydroxylase (DbetaH),
      in medullary and pontine cell groups that innervate the central nucleus of the
      amygdala (CeA) in rats. To identify such neurons, retrograde neural tracers were
      microinjected bilaterally into the CeA. Seven to 10 days later, rats were
      injected intraperitoneally with saline vehicle (controls) or cholecystokinin
      octapeptide (CCK, 10 microgram/kg) to stimulate gastric vagal afferents, then
      perfused with fixative 60-90 min later. Brain sections were processed for
      localization of neural tracer and cFos protein (to identify activated cells).
      Approximately 30% of retrogradely labeled neurons in the nucleus of the solitary
      tract (NST, A2/C2 region) and 19% of retrogradely labeled neurons in the
      ventrolateral medulla (VLM, A1/C1 region) were activated in rats after CCK
      treatment. Triple immunolabeling of cFos, neural tracer, and DbetaH confirmed
      that the large majority of activated, CeA-projecting neurons were noradrenergic
      (or adrenergic). Conversely, CCK activated less than 4% of CeA-projecting neurons
      in the locus coeruleus (LC, A6 cell group), similar to control cases. These
      findings suggest that vagal afferent stimulation may modify amygdalar processes
      of emotional learning via direct noradrenergic/adrenergic projections from the
      caudal medulla to the CeA.

PMID- 12527027
TI  - Controls of vasopressin secretion and thirst: similarities and dissimilarities in
      signals.
AB  - RATS HAVE TWO PROMINENT RESPONSES TO DEHYDRATION: secretion of the antidiuretic
      hormone, vasopressin (VP), and thirst. Many signals directly affect both
      responses. These include two excitatory signals associated with increased plasma
      osmolality (pOsm) and two inhibitory signals associated with decreased pOsm (one
      each from cerebral and visceral osmoreceptors). In addition, both VP secretion
      and thirst during hypovolemia are stimulated by at least two signals, one neural
      (from cardiac baroreceptors) and one humoral (i.e., angiotensin II). In contrast
      to these evident similarities, there are definite dissimilarities in the signals
      for VP secretion and thirst. For example, acute hypervolemia inhibits VP
      secretion but not thirst, whereas acute hypertension inhibits thirst but not VP
      secretion. Thirst and VP secretion in rats each are stimulated by acute arterial
      hypotension, albeit not by the same signals; water intake is mediated by
      activation of the renin-angiotensin system but not by a neural signal from
      arterial baroreceptors, whereas the reverse may be true for the stimulation of VP
      secretion. These dissimilarities indicate that VP secretion and thirst in rats
      are neither invariably linked nor controlled by the same mechanisms.

PMID- 12527028
TI  - The locus coeruleus, Barrington's nucleus, and neural circuits of stress.
AB  - Much attention has focused on the role of the locus coeruleus (LC) as a component
      of the central neural circuitry involved in stress. Many, though not all,
      stressful stimuli produce activation of LC neurons, as reflected by increased Fos
      expression in these neurons. Stimulation of the LC elicits many stress-like
      responses, including increased ACTH secretion, though not all responses to LC
      stimulation are readily interpretable in the context of stress. In particular,
      stimulation of the LC, at least in anesthetized rats, elicits a decrease in blood
      pressure and heart rate. Inhibition of the LC has been reported to inhibit
      certain responses to stress, including inhibition of ACTH release in response to
      certain stressors. Furthermore, local inhibition of the LC prevents foot shock
      evoked Fos expression in certain brain areas. In the studies of the role of the
      LC in stress, one complicating factor has been the inadequate attention given to
      Barrington's nucleus (BN), which is located adjacent to the LC. Although BN is
      best recognized for its role in the control of micturition, the fact that it is
      activated by a great variety of stressful stimuli, and that it is anatomically
      connected to multiple output systems involved in stress responses, suggest that
      it may play a role in the neural circuitry subserving responses to stress.

PMID- 12527029
TI  - Does the vestibular system contribute to head direction cell activity in the rat?
AB  - Head direction cells (HDC) located in several regions of the brain, including the
      anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral
      mammillary nuclei (LMN), provide the neural substrate for the determination of
      head direction. Although activity of HDC is influenced by various sensory signals
      and internally generated cues, lesion studies and some anatomical and
      physiological evidence suggest that vestibular inputs are critical for the
      maintenance of directional sensitivity of these cells. However, vestibular inputs
      must be transformed considerably in order to signal head direction, and the
      neuronal circuitry that accomplishes this signal processing has not been fully
      established. Furthermore, it is unclear why the removal of vestibular inputs
      abolishes the directional sensitivity of HDC, as visual and other sensory inputs
      and motor feedback signals strongly affect the firing of these neurons and would
      be expected to maintain their directional-related activity. Further physiological
      studies will be required to establish the role of vestibular system in producing
      HDC responses, and anatomical studies are needed to determine the neural
      circuitry that mediates vestibular influences on determination of head direction.

PMID- 12527030
TI  - Contractile responses of the human umbilical artery to KCl and serotonin in Ca
      free medium and the effects of levcromakalim.
AB  - It is known that K(ATP) channel openers inhibit the release and refilling of
      Ca(2+) from intracellular stores. The present study was designed to test the
      effects of levcromakalim in human umbilical artery (HUA) rings stimulated by
      serotonin (5-HT) and KCl in Ca-free medium. Umbilical cords were obtained at
      vaginal or cesarean deliveries from healthy, term pregnancies. After the
      isolation, HUA rings were placed in organ baths in solution with indomethacin
      (10(-5) M) and N(G)-nitro-L-arginine methyl ester (L-NAME) (10(-3) M) at 37
      degrees C and aerated with 95% O(2) and 5% CO(2) for the measurement of isometric
      force. In Ca-free solution with Ethylene glycol-bis (ss-aminoethyl ether)
      N,N,N',N'-tetraacetic acid (EGTA) (2 mM) the contractions produced by 5-HT (10(
      6) M) and KCl (40 mM) decreased significantly. Afterwards, HUA rings were treated
      with 5-HT and KCl in repeated manner in Ca-free medium. In contrast to KCl, 5-HT
      induced contractions reduced in each application, progressively. Levcromakalim
      (10(-4) M) abolished the contractions elicited by 5-HT. On the other hand,
      levcromakalim had a little but significant inhibitory effect on KCl induced
      contraction in Ca-free medium. These results suggest that Ca(2+) is not the only
      transduction pathway in KCl produced contractions of HUA smooth muscle cells.

PMID- 12527031
TI  - IFN-gamma production in rabbits: behavioral and endocrine correlates.
AB  - Freely interacting male rabbits were studied to establish the effect of exogenous
      testosterone on interferon-gamma (IFN-gamma) production in peripheral blood
      mononuclear cells (PBMCs) and to evaluate if this effect is related to season,
      social rank, plasma corticosterone and glucocorticoid receptors (GcR) in PBMCs.
      Dominance behavior increases after testosterone propionate (TP) administration
      only in rank 1 animals, while submission behavior increases after TP only in rank
      4 animals, indicating a reinforcing effect of TP on the behavior. Corticosterone
      and IFN-gamma production are higher and GcR binding capacity is lower in spring
      than in autumn, suggesting that seasonal fluctuations in the immune system may be
      related to the pattern of secretion of immunomodulatory hormones. In autumn,
      corticosterone decreases after TP treatment and increases after social
      interaction, while GcR binding capacity decreases after TP treatment and social
      interaction. IFN-gamma production decreases in spring and increases in autumn
      after TP treatment plus social interaction, indicating that the modulating action
      of testosterone is related to the current immune status. The relationship between
      dominance, testosterone and the immune system in spring is suggested by the
      finding that GcR binding capacity after TP treatment is directly related to
      social rank, as confirmed by the positive correlation with dominance behavior
      frequency. The dominance index is positively correlated with GcR binding capacity
      and negatively with IFN-gamma production before TP treatment, indicating that
      high receptor activity in immunocompetent cells and low immunoreactivity could be
      prerequisites for dominance behavior. The immunosuppressive effect of
      corticosterone and the mechanism of down-regulation on GcR are confirmed by the
      negative correlations with IFN-gamma production and GcR binding capacity.

PMID- 12527032
TI  - Anticlastogenic effect of Spirulina maxima extract on the micronuclei induced by
      maleic hydrazide in Tradescantia.
AB  - The aim of this investigation was to determine if extracts of Spirulina maxima
      reduce the genotoxic damage induced by maleic hydrazide (MH) using the
      Tradescantia biosssay. Two types of extracts from the alga were prepared: an
      aqueous extract with two different concentrations, 100 and 500 mg/ml, and a
      second one, the extract of a 1% solution of dimethyl sulfoxide (DMSO) which
      corresponded to 100 mg/ml of the alga. The capacity of MH to induce micronuclei
      (MN) was initially established by administering 0.005, 0.01, and 0.015 mg/ml of
      the chemical to the Tradescantia inflorescences, and observing its effect after
      24 h.The results of this experiment showed a significant MN increase with the two
      high concentrations tested, although no dose-response effect was observed. For
      the anticlastogenic assay, the extracts of Spirulina were applied to the
      inflorescences alone or immediately before the application of MH (0.01 mg/ml) and
      the induced MN were observed 24 h later. We found that none of the extracts
      increased the MN level with respect to the untreated plants; also, that MH more
      or less doubled the basal micronuclei frequency, and finally, that all tested
      extracts reduced the genotoxic damage caused by MH. The inhibitory indices
      obtained for the aqueous extracts (100 and 500 mg/ml) and for the DMSO extract
      were respectively 59, 85, and 56.3%. These data indicate that Spirulina is an
      anticlastogenic agent and suggest that it is advisable to extend studies on this
      matter using other biological models.

PMID- 12527033
TI  - Repeated citalopram treatment but not stress exposure attenuates hypothalamic
      pituitary-adrenocortical axis response to acute citalopram injection.
AB  - Many experimental, clinical and epidemiological studies have shown a direct
      connection between exposure to stress or adverse life events and disease, but
      little is known about the effect of stress on the action of drugs. The aim of
      this study was to test the hypothesis that previous exposure to stress changes
      the action of the antidepressant drug citalopram (10 mg/kg, i.p.) on hypothalamic
      pituitary-adrenocortical (HPA) axis function, gene expression of selected
      neuropeptides and serotonin reuptake. Three different stress models were used,
      which included immobilization, restraint and unpredictable stress stimuli.
      Samples of plasma for hormone measurement were taken from conscious cannulated
      animals. Changes in corticotropin-releasing hormone (CRH) and proopiomelanocortin
      (POMC) gene expression in the paraventricular nucleus of the hypothalamus and the
      anterior pituitary, respectively, and the ability of citalopram to inhibit
      serotonin reuptake were investigated. The exposure to three different stress
      models did not influence citalopram action on individual parameters of HPA axis
      and on serotonin reuptake. On the other hand, repeated administration of the drug
      led to significant attenuation of ACTH and CRH mRNA responses. The present
      results allow to suggest that the stressors used did not influence serotonergic
      neurotransmission to the extent that would modify HPA axis response to citalopram
      challenge. Activation of HPA axis by acute citalopram treatment was found to be
      accompanied by increased CRH gene expression in the hypothalamus. Repeated
      administration of the drug led to the development of tolerance to activation of
      central and peripheral components of HPA axis, but not to serotonin reuptake
      inhibition.

PMID- 12527034
TI  - 6-Hydroxymelatonin converts Fe (III) to Fe (II) and reduces iron-induced lipid
      peroxidation.
AB  - Disorders of iron accumulation are known to produce hepatotoxicity. Agents, which
      can reduce Fe(3+) to a more usable form Fe(2+) could potentially limit such
      damage. Since it has been previously demonstrated that the pineal secretory
      product, melatonin, is able to bind iron, we decided to investigate the potential
      protective properties of the principal melatonin metabolite and degradant, 6
      hydroxymelatonin (6-OHM). Using adsorptive cathode stripping voltammetry (AdCSV)
      we showed that Fe(3+) in the presence of 6-OHM is converted to Fe(2+). We further
      demonstrated that 6-OHM reduces the Fe(2+)-induced rise in lipid peroxidation in
      rat liver homogenates. The results imply that 6-OHM facilitates the conversion of
      Fe(3+) to Fe(2+) which is a more biologically usable form of iron. While such a
      conversion could also potentially make more Fe(2+) available for driving the
      Fenton reaction and the consequent generation of the dangerous hydroxyl radical,
      6-OHM is able to quench these radicals, thereby providing tissue protection.

PMID- 12527035
TI  - Effect of PKC412, a selective inhibitor of protein kinase C, on lung metastasis
      in mice injected with B16 melanoma cells.
AB  - PKC412, a selective inhibitor of protein kinase C (PKC), is currently in clinical
      trials as an anti-tumor drug. In the present study, we investigated the anti
      metastatic effect of PKC412 using an experimental metastatic mouse model
      intravenously injected with melanoma cells. One-hour exposure to various
      concentrations of PKC412 (0.5, 5 and 50 microM) dose-dependently reduced the lung
      metastatic potential of highly metastatic B16-F10 and -BL6 mouse melanoma cells
      in syngeneic mice. Following the exposure, PKC activities in B16-F10 and -BL6
      cells were significantly decreased, but growth curves were not influenced. To
      elucidate the mechanism of the anti-metastatic effect of PKC412, we examined the
      activity to invade the extracellular matrix and the platelet-aggregating activity
      of the melanoma cells incubated with PKC412 (0.5, 5 and 50 microM) for 1 hour.
      PKC412 significantly reduced both the invasive and platelet-aggregating
      activities. These results suggest that PKC412 shows an anti-metastatic function
      through the inhibition of the invasive and/or platelet-aggregating activities of
      melanoma cells. PKC412 is potentially a promising candidate for an anti
      metastatic agent.

PMID- 12527036
TI  - Oxysterols induce apoptosis and accumulation of cell cycle at G(2)/M phase in the
      human monocytic THP-1 cell line.
AB  - The cytotoxic activity of oxysterols, 7 beta-hydroxycholesterol (7 beta-OHC) and
      25-hydroxycholesterol (25-OHC), has been evaluated using various leukemia cell
      lines. Among the tested cell lines, both oxysterols showed the highest
      cytotoxicity to THP-1, human monocytic leukemia cell line. These oxysterols
      induced apoptosis through down-regulation of Bcl-2 expression and activation of
      caspases. Also, the oxysterols showed the accumulation at G(2)/M phase of cell
      cycle through down-regulation of cyclin B1 expression. Taken together, these
      results indicated that both 7 beta-OHC and 25-OHC inhibited the proliferation of
      THP-1 cells through apoptosis and cell cycle accumulation at G(2)/M phase.

PMID- 12527037
TI  - Effects of bile acids on biliary epithelial cells: proliferation, cytotoxicity,
      and cytokine secretion.
AB  - Hydrophobic bile acids, which are known to be cytotoxic for hepatocytes, are
      retained in high amount in the liver during cholestasis. Thus, we have
      investigated the effects of bile acids with various hydrophobicities on biliary
      epithelial cells. Biliary epithelial cells were cultured in the presence of
      tauroursodeoxycholate (TUDC), taurocholate (TC), taurodeoxycholate (TDC),
      taurochenodeoxycholate (TCDC), or taurolithocholate (TLC). Cell proliferation,
      viability, apoptosis and secretion of monocyte chemotactic protein-1 (MCP-1) and
      of interleukin-6 (IL-6) were studied. Cell proliferation was increased by TDC,
      and markedly decreased by TLC in a dose dependent manner (50-500 microM). Cell
      viability was significantly decreased by TLC and TCDC at 500 microM. TLC, TDC and
      TCDC induced apoptosis at high concentrations. The secretion of MCP-1 and IL-6
      was markedly stimulated by TC. TUDC had no significant effect on any parameter.
      These findings demonstrate that hydrophobic bile acids were cytotoxic and induced
      apoptosis of biliary epithelial cells. Furthermore, TC, a major biliary acid in
      human bile, stimulated secretion of cytokines involved in the inflammatory and
      fibrotic processes occurring during cholestatic liver diseases.

PMID- 12527038
TI  - The L-DOPA-sparing effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane
      hydrochloride [(-)-BPAP] in reserpine-pretreated rats.
AB  - R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP], a highly
      potent enhancer of impulse propagation-mediated release of catecholamines and
      serotonin in the brain, and significantly increased the locomotor activity of
      normal rats at the doses of 0.3 and 1 mg/kg s.c. (P < 0.05), while L-DOPA (200
      and 400 mg/kg i.p.) had no significant effect. The locomotor activity of rats
      simultaneously administered L-DOPA and (-)-BPAP was significantly higher than
      with (-)-BPAP alone (P < 0.05). In rats pretreated with reserpine (1 mg/kg i.v.),
      the hypolocomotion was significantly reversed by 400 mg/kg i.p. L-DOPA, or 1 or 3
      mg/kg s.c. (-)-BPAP (P < 0.05). Furthermore, the combined administration of
      subthreshold doses of 200 mg/kg i.p. L-DOPA and 0.3 mg/kg s.c. (-)-BPAP highly
      potentiated the locomotor activity in the reserpine-pretreated rats. However, (-)
      BPAP failed to reverse the hypolocomotion in rats pretreated with reserpine +
      alpha-methyl-DL-p-tyrosine. Thus, (-)-BPAP was demonstrated to possess the L-DOPA
      sparing effect in normal and reserpine-pretreated rats.

PMID- 12527039
TI  - Dependence of rat hippocampal c-Fos expression on intensity and duration of
      exercise.
AB  - The expression of c-Fos, an immediately early gene, is a marker of neural
      activity. In the present study, the effect of treadmill exercise on c-Fos
      expression was investigated in various regions of the rat hippocampus via
      immunohistochemistry. The first part of the experiment was aimed at determining
      the dependence of c-Fos expression on the intensity of treadmill exercise. In
      most of the hippocampal regions studied, increasing c-Fos expression was observed
      with increasing exercise intensity. In the second part of the experiment, the
      dependence of c-Fos expression on the duration of treadmill exercise was
      investigated. The c-Fos expression induced by mild-intensity exercise increased
      until the 7th day of exercise and subsequently decreased. Results of the present
      study suggest that the effect of treadmill exercise on neuronal activity in the
      hippocampus is intensity-and duration-dependent.

PMID- 12527040
TI  - Initial clinical experience with the MammoSite breast brachytherapy applicator in
      women with early-stage breast cancer treated with breast-conserving therapy.
AB  - PURPOSE: We present the results of the initial clinical testing of the MammoSite
      balloon breast brachytherapy applicator in women with early-stage breast cancer
      treated with breast-conserving therapy. METHODS AND MATERIALS: Seventy patients
      were enrolled in a multicenter prospective trial testing the applicator for
      safety and performance. Fifty-four patients were implanted, and 43 patients were
      ultimately eligible for and received brachytherapy as the sole radiation modality
      after lumpectomy. Patients were staged T1N0M0 with negative pathologic margins
      and age >45 years. A dose of 34 Gy was delivered in 10 fractions over 5 days
      prescribed to 1 cm from the applicator surface using 192Ir high-dose-rate
      brachytherapy. A minimum skin-to-balloon surface distance of 5 mm was required
      for treatment. Device performance, complications, and cosmesis were assessed.
      RESULTS: Computed tomography imaging post-balloon inflation showed 8, 14, and 21
      patients with 5-6 mm, 7-9 mm, and >10 mm of skin spacing, respectively. Two
      patients were explanted because of inadequate skin spacing and 7 because of
      suboptimal conformance of the surgical cavity to the applicator balloon. One
      patient was explanted because of positive nodal status and another because of
      age. The most common side effects related to device placement included mild
      erythema, drainage, pain, and echymosis. No severe side effects related to
      implantation, brachytherapy, or explantation occurred. Side effects related to
      radiation therapy were generally mild with erythema, pain, and dry desquamation
      being the most common. At 1 month, 88% of patients were evaluated as having good
      to-excellent cosmetic results. CONCLUSIONS: The MammoSite balloon breast
      brachytherapy applicator performed well clinically. All eligible patients
      completed treatment. Side effects were mild to moderate and self-limiting. Skin
      balloon surface distance and balloon-cavity conformance were the main factors
      limiting the initial use of the device.

PMID- 12527041
TI  - Molecular (functional) imaging for radiotherapy applications: an RTOG symposium.

PMID- 12527042
TI  - Accelerated partial breast irradiation using 3D conformal radiation therapy (3D
      CRT).
AB  - PURPOSE: We present a novel three-dimensional conformal radiation therapy (3D
      CRT) technique to treat the lumpectomy cavity, plus a 1.5-cm margin, in patients
      with early-stage breast cancer and study its clinical feasibility. METHODS AND
      MATERIALS: A 3D-CRT technique for partial-breast irradiation was developed using
      archived CT scans from 7 patients who underwent an active breathing control
      study. The clinical feasibility of this technique was then assessed in 9 patients
      who were prospectively enrolled on an Investigational Review Board-approved
      protocol of partial-breast irradiation. The prescribed dose was 34 Gy in 5
      patients and 38.5 Gy in 4 patients, delivered in 10 fractions twice daily over 5
      consecutive days. The impact of both breathing motion and patient setup
      uncertainty on clinical target volume (CTV) coverage was studied, and an
      appropriate CTV-to-PTV (planning target volume) margin was calculated. RESULTS:
      By adding a CTV-to-PTV "breathing-only" margin of 5 mm, 98%-100% of the CTV
      remained covered by the 95% isodose surface at the extremes of normal inhalation
      and normal exhalation. The "total" CTV-to-PTV margin employed to accommodate
      organ motion and setup error (10 mm) was found to be sufficient to accommodate
      the observed uncertainty in the delivery precision. Patient tolerance was
      excellent, and acute toxicity was minimal. No skin changes were noted during
      treatment, and at the initial 4-8-week follow-up visit, only mild localized
      hyperpigmentation and/or erythema was observed. No instances of symptomatic
      radiation pneumonitis have occurred. CONCLUSIONS: Accelerated partial-breast
      irradiation using 3D-CRT is technically feasible, and acute toxicity to date has
      been minimal. A CTV-to-PTV margin of 10 mm seems to provide coverage for most
      patients. However, more patients and additional studies will be needed to
      validate the accuracy of this margin, and longer follow-up will be needed to
      assess acute and chronic toxicity, tumor control, and cosmetic results.

PMID- 12527043
TI  - Patterns of failure in patients receiving definitive and postoperative IMRT for
      head-and-neck cancer.
AB  - PURPOSE: To analyze the patterns of locoregional failure in patients with head
      and-neck cancer treated with inverse planning intensity-modulated radiotherapy
      (IMRT). METHODS AND MATERIALS: Between February 1997 and December 2000, 165
      patients with histologically confirmed head-and-neck cancer were treated using a
      parotid-sparing inverse planning IMRT protocol. Thirty-nine patients who received
      either palliative repeat irradiation or IMRT as a boost were excluded from this
      analysis, leaving 126 patients for this analysis. Of the 126 patients, 30 were
      women and 96 were men (median age 56 years, range 13-84). Fifty-two patients
      (41%) received definitive IMRT. Of the 52 patients, 17 were treated with RT alone
      and 35 with concurrent cisplatin-based chemotherapy regimens. Seventy-four
      patients (59%) received postoperative IMRT. The median follow-up was 26 months
      (range 12-55). IMRT was used only in the upper neck for salivary sparing. The
      lower neck was treated with a conventional AP low-neck port abutted to the
      inferior IMRT dose distribution border. The radiation dose was prescribed to the
      two clinical target volumes (CTVs) according to the assumed risk of containing
      disease. The mean dose for definitive IMRT patients was 72.64 +/- 4.83 Gy to CTV1
      and 64.34 +/- 5.15 Gy to CTV2. The mean dose to CTV1 and CTV2 in postoperative
      cases was 68.53 +/- 4.71 Gy and 60.95 +/- 5.33 Gy, respectively. The locations of
      failure were analyzed. RESULTS: Seventeen locoregional failures (persistent or
      recurrent disease) were found. Of these 17 failures, 9 (53%) were inside CTV1.
      One failure (6%) was marginal to CTV1 but inside CTV2. One failure (6%) occurred
      outside CTV1 but inside CTV2. Another failure was marginal to CTV2. Of the 17
      failures, 5 (28%) were found outside of the IMRT field and in the lower neck.
      Dose-volume histogram analysis revealed that for all but 1 patient, the
      recurrent/persistent disease within the CTVs received comparable or superior dose
      coverage relative to the CTV. The 2-year actuarial locoregional control rate was
      85%, and the ultimate locoregional control rate after surgical salvage was 89%.
      We observed no dermal failure and only one marginal failure in the region
      adjacent to the spared parotid glands. CONCLUSION: We have shown that the target
      definition and coverage for patients treated with IMRT for parotid sparing is
      adequate. The predominant tumor failure within CTV1 may imply the need to
      identify patients with radioresistant tumor subvolumes (such as hypoxic regions)
      within the CTV. This information would assist in discriminating a subgroup of
      tumors for a more aggressive and target-specific therapeutic approach.

PMID- 12527044
TI  - Results of radiotherapy for T2N0 glottic carcinoma: does the "2" stand for twice
      daily treatment?
AB  - PURPOSE: Radiotherapy (RT) is often the therapy of choice for patients with Stage
      T2 glottic carcinoma. This retrospective study updated the results of RT for
      patients treated at our center. The primary focus of this study was whether a
      policy of using hyperfractionated RT for these patients resulted in a therapeutic
      gain. METHODS AND MATERIALS: A search of the database of patients treated in the
      Department of Radiation Oncology at The University of Texas M. D. Anderson Cancer
      Center was performed to identify patients with Stage T2 glottic carcinoma treated
      with RT alone between 1970 and 1998. A total of 230 patients formed the study
      cohort. RESULTS: The median follow-up for all patients was 82 months. Of the 230
      patients, 180 were treated with parallel-opposed fields, and the median field
      size was 30 cm(2). Eighty-one patients (36%) were treated with twice-daily
      fractionation to 74-80 Gy. Eighty-nine patients (38%) were treated with 32-75 Gy
      at 2-Gy per fraction once daily, and 57 patients (25%) were treated with 2.06
      2.26 Gy, once daily, to 66-70 Gy. The 2- and 5-year actuarial local control rate
      was 75% and 72%, respectively. After salvage therapy, the ultimate 5-year local
      control and disease-specific survival rate was 91% and 92%, respectively. The
      presence of subglottic extension and treatment with a daily dose of < or =2 Gy
      were associated with poorer local control (p <0.01) on both univariate and
      multivariate analyses. The 5-year local control rate for patients treated with
      twice-daily and once-daily RT was 79% and 67%, respectively (p = 0.06).
      CONCLUSION: The 5-year local control rates with hyperfractionated RT for Stage T2
      glottic carcinoma approach 80%. Patients treated with twice-daily fractionation
      to a median dose of 77 Gy had an improvement in local control compared with
      patients treated with 70 Gy in 35 fractions. The Radiation Therapy Oncology Group
      is testing these two fractionation schedules in a randomized study. High control
      rates were also seen in selected patients treated with hypofractionated
      schedules, leaving the question of the optimal schedule for patients with Stage
      T2 disease unanswered.

PMID- 12527045
TI  - Clinical results and prognostic factors in radiotherapy for unresectable
      hepatocellular carcinoma: a retrospective study of 158 patients.
AB  - PURPOSE: To analyze the treatment results and prognostic factors affecting
      survival in patients with unresectable hepatocellular carcinoma treated with
      local radiotherapy (RT). METHODS AND MATERIALS: Between 1992 and 2000, 158
      patients with unresectable hepatocellular carcinoma received local RT. Sixty
      seven patients had an advanced UICC Stage III lesion and 91 patients had Stage
      IVA. The mean tumor size was 9.0 +/- 3.0 cm, and liver cirrhosis was present in
      142 patients. Local RT was combined with transarterial chemoembolization as
      primary treatment (107 patients) or as salvage after failure of repeated
      transarterial chemoembolization (51 patients). The mean radiation dose was 48.2
      +/- 7.9 Gy in daily 1.8-Gy fractions. RESULTS: The mean follow-up was 21.6 months
      after diagnosis and 14.6 months after RT. The response rate was 67.1%. The
      overall survival rate at 2 and 5 years was 30.5% and 9%, respectively, from the
      time of diagnosis (median survival time 16 months) and 19.9% and 4.7%,
      respectively, after RT (median survival time 10 months). On univariate analysis,
      tumor size (p = 0.047), the presence of portal vein thrombosis (p = 0.007), and
      RT dose (p = 0.001) were significant factors for survival. However, on
      multivariate analysis, RT dose was the only significant factor (p = 0.01).
      CONCLUSION: Local RT achieved substantial tumor regression and survival. The
      radiation dose was found to be a significant prognostic factor in the RT of
      hepatocellular carcinoma. Additional efforts for dose escalation are warranted to
      improve the treatment results in parallel with better protecting the nontumorous
      liver.

PMID- 12527046
TI  - Predictors of radiation-induced esophageal toxicity in patients with non-small
      cell lung cancer treated with three-dimensional conformal radiotherapy.
AB  - PURPOSE: To evaluate the incidence and clinical/dosimetric predictors of acute
      and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in
      patients with non-small-cell lung cancer (NSCLC) treated with definitive three
      dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: We
      retrospectively reviewed the charts of 207 consecutive patients with NSCLC who
      were treated with high-dose, definitive 3D-CRT between March 1991 and December
      1998. This population consisted of 107 men and 100 women. The median age was 67
      years (range 31-90). The following patient and treatment parameters were studied:
      age, gender, race, performance status, sequential chemotherapy, concurrent
      chemotherapy, presence of subcarinal nodes, pretreatment weight loss, mean dose
      to the entire esophagus, maximal point dose to the esophagus, and percentage of
      volume of esophagus receiving >55 Gy. All doses are reported without
      heterogeneity corrections. The median prescription dose to the isocenter in this
      population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All
      patients were treated once daily. Acute and late esophageal toxicities were
      graded by Radiation Therapy Oncology Group criteria. Patient and
      clinical/dosimetric factors were coded and correlated with acute and late Grade 3
      5 esophageal toxicity using univariate and multivariate regression analyses.
      RESULTS: Of 207 patients, 16 (8%) developed acute (10 patients) or late (13
      patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late
      Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of
      late esophageal perforation. Concurrent chemotherapy, maximal point dose to the
      esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were
      significantly associated with a risk of Grade 3-5 esophageal toxicity on
      univariate analysis. Concurrent chemotherapy and maximal point dose to the
      esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients,
      53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who
      developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p =
      0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity
      occurred in patients who received a maximal point dose to the esophagus of <58 Gy
      (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5
      esophageal toxicity in the absence of concurrent chemotherapy; both received a
      maximal esophageal point dose >69 Gy. All assessable patients who developed Grade
      3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p =
      0.0351, Pearson's chi-square test). However, the mean dose was not predictive on
      multivariate analysis. CONCLUSION: Concurrent chemotherapy and the maximal
      esophageal point dose were significantly associated with a risk of Grade 3-5
      esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In
      patients who received concurrent chemotherapy, the threshold maximal esophageal
      point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of
      patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy
      to allow a valid statistical analysis of the relationship between the maximal
      esophageal point dose and esophagitis.

PMID- 12527047
TI  - Probability of late rectal morbidity in 125I prostate brachytherapy.
AB  - PURPOSE: Rectal toxicity is a concern in prostate brachytherapy because it is
      difficult to avoid delivering a dose equal to, or greater than, the prescription
      dose to the anterior surface of the rectum. The purpose of this study was to
      define the probability that a patient will experience Grade 2
      (bleeding/ulceration) late rectal morbidity after 125I prostate brachytherapy
      according to the rectal dosimetry. METHODS AND MATERIALS: Ninety-eight
      consecutive patients who received monotherapy 125I prostate implants for
      treatment of Stage T1-T2, favorable-risk adenocarcinoma of the prostate were
      evaluated for Radiation Therapy Oncology Group Grade 2 late rectal morbidity. All
      reported incidences of late morbidity were retrospectively confirmed by
      colonoscopy. All patients had at least 15 months follow-up after implantation.
      The median follow-up was 32 months (range 15-54). The rectal dosimetry was based
      on a CT scan obtained at 3-9 weeks after implantation. The rectum was contoured
      on each CT image between the base and apex of the prostate. A dose-surface
      histogram was compiled for each implant, and the relative surface area that
      received a dose > or =100, > or =150, > or =200, > or =300, > or =400, and > or
      =500 Gy was recorded. The probability of developing late rectal toxicity was
      calculated by logistic regression analysis as a function of dose and the
      percentage of the rectal surface that received that dose. RESULTS: Of the 98
      patients, 10 developed Grade 2 late rectal morbidity. The percentage of the
      rectal surface that received 100, 150, 200, and 300 Gy was significantly greater
      (p < or =0.02) for patients who experienced late rectal morbidity. The
      probability of late rectal morbidity increased with both the dose and the
      percentage of the rectal surface that received that dose. The probability was <
      or =1% when 20%, 7%, and 0% of the rectal surface received 100, 150, and 200 Gy,
      respectively. The probability increased to < or =5% when 31%, 19%, and 9% of the
      rectal surface received these doses. The probability of late rectal morbidity can
      also be expressed in terms of the maximal rectal dose. The probability of late
      morbidity was 0.4%, 1.2%, and 4.7% when the maximal rectal dose was 150, 200, and
      300 Gy, respectively. CONCLUSION: The percentage of the rectal surface that
      receives a dose > or =100 Gy is predictive of Grade 2 (bleeding/ulceration) late
      rectal morbidity after 125I prostate brachytherapy. The probability of late
      morbidity depends on both the dose and the percentage of the rectal surface that
      received that dose. Our results indicate that the rectum can tolerate doses of
      100, 150, and 200 Gy to approximately 30%, 20%, and 10% of the rectal surface
      with a < or =5% risk of late morbidity. Our results also indicate that the
      practical guideline for limiting the incidence of late morbidity to 1%, 3%, or 5%
      is to keep the maximal rectal dose to <200, 250, and 300 Gy, respectively.

PMID- 12527048
TI  - Nonoperative assessment of nodal status for locally advanced cervical squamous
      cell carcinoma treated by radiotherapy with regard to patterns of treatment
      failure.
AB  - PURPOSE: Lymph node metastasis is a major prognostic factor in the treatment of
      cervical cancer, but its nonsurgical assessment is not necessarily accurate,
      particularly in small nodes. We evaluated whether node-negative status could be
      accurately assessed using a low cutoff measure. METHODS AND MATERIALS: The
      subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma
      treated by definitive radiotherapy. Nodal status was assessed by CT as negative
      (<5 mm), possibly positive (5-10 mm), or probably positive (>10 mm). Cause
      specific survival and the disease-free rate, including the pelvic recurrence-free
      and distant metastasis-free rates, were estimated. RESULTS: The cause-specific
      survival, disease-free rate, and pelvic recurrence-free rate at 5 years were
      significantly higher for the 32 patients with node-negative disease (83.5%,
      86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%,
      93.8%, and 93.8%) than for the 35 patients with probably node-positive disease
      (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found
      between negative and possibly node-positive status. In contrast, the distant
      metastasis-free rate differed significantly among node-negative (96.4%), possibly
      node-positive (59.3%), and probably node-positive (35.1%) status. CONCLUSION:
      Node-negative status assessed using a strict cutoff measure may be useful as a
      strong predictor of cervical cancer being confined to the pelvis.

PMID- 12527049
TI  - Intensity modulated radiotherapy (IMRT) for recurrent, residual, or untreated
      skull-base meningiomas: preliminary clinical experience.
AB  - OBJECTIVE: To investigate the feasibility of using intensity modulated
      radiotherapy (IMRT) for complex-shaped benign meningiomas of the skull base and
      report clinical experience. METHODS: Twenty patients with benign skull-base
      meningiomas WHO degrees I (histopathologically proven in 16/20) were treated with
      IMRT between June 1998 and August 1999. Each tumor was complex in shape and
      adherent to, or encompassed, organs at risk (cranial nerves, optic apparatus, and
      brainstem). All patients, immobilized in a customized head mask integrated into a
      stereotactic system, were planned on an inverse treatment planning system using 5
      or 7 coplanar, equidistant beams and 5 intensity steps. Each treatment plan was
      verified extensively before treatment. Follow-up with MRI and clinical
      examination was performed at 6 and 18 weeks and every 6 months thereafter.
      RESULTS: Target volumes ranged from 27 to 278 cc (median: 108 cc). Mean dose in
      32 fractions ranged between 55.8 and 58.2 Gy. At median follow-up of 36 months
      (range: 31-43 months), pre-existing neurologic symptoms improved in 12/20 (60%),
      remained stable in 7/20 (35%), and worsened in 1 (5%) patient. Radiographic
      follow-up revealed significant tumor shrinkage 6 weeks post-IMRT in 2 patients
      and partial remission in 3 more patients at 9-17 months; other tumor volumes
      remained stable. There was no radiation-induced peritumoral edema, increase in
      tumor size, or new onset of neurologic deficits. Transient acute treatment side
      effects included nausea and vomiting and single occurrences of
      conjunctivitis/increased tearing and serous tympanitis. CONCLUSION: IMRT in the
      treatment of central nervous system meningiomas is feasible and safe, offering
      highly conformal irradiation for complex-shaped skull-base tumors while sparing
      adjacent critical structures. If the tumor remissions seen here are found in the
      ongoing treatments, IMRT may be considered the treatment of choice for inoperable
      or subtotally resected meningiomas and for otherwise difficult-to-treat, complex
      shaped tumors of the central nervous system adjacent to critical structures, with
      the potential of dose escalation for malignant tumors.

PMID- 12527050
TI  - Defining the optimal dose of radiation after incomplete resection of central
      neurocytomas.
AB  - PURPOSE: Central neurocytomas are uncommon benign central nervous system tumors.
      There is uncertainty regarding the most appropriate radiation dose after
      incomplete resection. This analysis was performed to determine the optimal dose.
      METHODS AND MATERIALS: All cases reported since 1982 were reviewed for age,
      gender, resection status, total dose, dose per fraction, local control, and
      overall survival. Additional data were obtained from the authors. The inclusion
      criteria were incomplete resection, postoperative irradiation, complete data, and
      12 months' minimal follow-up. Two groups were formed according to the equivalent
      dose in 2-Gy fractions (EQD2): group A (40.0-53.6 Gy) and group B (54.0-62.2 Gy).
      Local control and survival were compared using Kaplan-Meier analysis and the log
      rank test. RESULTS: Eighty-nine patients (group A 42, group B 47) met the
      inclusion criteria. At 5 years, the local control rate was 98% for group B vs.
      69% for group A. At 10 years, it was 89% vs. 65% (p = 0.0066). The 5- and 10-year
      survival rate was 98% for group B vs. 88% for group A (p = 0.1). CONCLUSIONS: Our
      data suggest that a EQD2 > or =54 Gy significantly improves local control in
      patients with subtotally resected neurocytomas. Although the difference in
      survival was not significant, a trend toward better survival was noted after a
      EQD2 of > or =54 Gy.

PMID- 12527051
TI  - The determination of radiobiologically optimized half-lives for radionuclides
      used in permanent brachytherapy implants.
AB  - PURPOSE: To use tumor growth kinetics and other biologic parameters in an
      extended version of the linear-quadratic (LQ) formulation to determine
      radiobiologically optimized half-lives of radionuclides which might be used in
      permanent brachytherapy implants. METHODS AND MATERIALS: A version of the LQ
      model suitable for the analysis of permanent brachytherapy implants has been
      modified to investigate the radionuclide half-lives that will maximize the
      biologically effective dose (BED) delivered to tumors with repopulation rates (K
      values) in the range 0.01-1.1 Gyday(-1). The method assumes that part of the
      physical dose delivered to the tumor may be radiobiologically wasted because of
      the repopulation phenomenon, whereas adjacent normal tissues will exhibit little
      or no wastage. To perform the analysis, it is necessary to stipulate alpha/beta
      ratios and sublethal damage recovery rates together with the normal tissue
      tolerance BED. The analysis also takes into account a range of likely relative
      biological effectiveness (RBE) values. RESULTS: Rapidly growing tumors require
      the shortest radionuclide half-lives, but even slow-growing tumors such as
      prostate adenocarcinomas can be satisfactorily treated with radionuclides
      possessing half-lives substantially less than that associated with I(125). The
      likelihood that prostate tumors possess an alpha/beta value which is comparable
      with, or lower than, that associated with late-responding normal tissues would
      also mitigate against the use of long-lived radionuclides. Although a number of
      parameter assumptions are involved, the results suggest that, for a wide range of
      tumor types, shorter-lived radionuclides are more versatile for achieving
      reasonable clinical results. The theoretically derived optimum half-lives
      typically range from around 0-5 days for fast-repopulating tumors (K 1.1 Gyday(
      1)) to approximately 14-50 days for slow-growing tumors (K approximately 0.1
      Gyday(-1) or less). For prostate implantation, 103Pd is overall a better choice
      than 125I. CONCLUSION: With so many variables and parameter uncertainties, it is
      not appropriate to attempt to define optimum radionuclide half-lives too closely.
      However, this study suggests that half-lives in the approximate range 4-17 days
      are likely to be significantly better for a wide range of tumor types for which
      the radiobiologic characteristics may not be precisely known in advance.

PMID- 12527052
TI  - Radiation dose to conceptus resulting from tangential breast irradiation.
AB  - PURPOSE: To estimate the radiation dose to the conceptus resulting from
      tangential breast irradiation. METHODS AND MATERIALS: Conceptus radiation doses
      were measured in anthropomorphic phantoms simulating the geometry of a pregnant
      woman at the first, second, and third trimesters of gestation. Medial and lateral
      field irradiations were generated using a 6-MV X-ray beam. Dose measurements were
      performed with thermoluminescent dosimeters. RESULTS: For a treatment course
      delivering 50 Gy to the tumor, conceptus dose at the first trimester of gestation
      was found to be 2.1-7.6 cGy, depending on the field size used and the distance
      between conceptus and primary irradiation field. The corresponding dose ranges to
      the conceptus during the second and third trimesters of gestation were 2.2-24.6
      cGy and 2.2-58.6 cGy, respectively. Dose data and formulas are presented to
      estimate conceptus dose for individual patients undergoing breast radiotherapy
      during the entire pregnancy. CONCLUSIONS: This study may be of value in the
      management of pregnant women needing tangential breast irradiation, because it
      provides the required information to estimate conceptus dose.

PMID- 12527053
TI  - Significant reductions in heart and lung doses using deep inspiration breath hold
      with active breathing control and intensity-modulated radiation therapy for
      patients treated with locoregional breast irradiation.
AB  - PURPOSE: To evaluate the heart and lung sparing effects of moderate deep
      inspiration breath hold (mDIBH) achieved using an active breathing control (ABC)
      device, compared with free breathing (FB) during treatment with deep tangents
      fields (DT) for locoregional (LR) irradiation of breast cancer patients,
      including the internal mammary (IM) nodes (IMNs). To compare the DT-mDIBH
      technique to other standard techniques and to evaluate the dosimetric effect of
      intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Fifteen
      patients (9 left-sided and 6 right-sided lesions) with Stages 0-III breast cancer
      underwent standard FB and ABC computed tomographic (CT) scans in the treatment
      position. A dosimetric planning study was performed. In FB, the 9 left-sided
      patients were planned with a 5-field technique where electron fields covering the
      IM region were matched to shallow tangents using wedges (South West Oncology
      Group [SWOG] protocol S9927 technique A). This method was compared with a 3-field
      DT technique covering the breast and the IMNs (SWOG S9927 technique B).
      Compensation with IMRT was then compared with wedges for each technique. For the
      15 total patients, dosimetric planning using DT with IMRT was then reoptimized on
      the mDIBH CT data set for comparison. Dose-volume histograms for the clinical
      target volume (CTV) (including the IMNs), planning target volume (PTV),
      ipsilateral and contralateral breast, and organs at risk (OAR) were analyzed. In
      addition, normal tissue complication probabilities (NTCP) for lung and heart,
      mean lung doses, and the number of monitor units (MUs) for a 1.8 Gy fraction were
      compared. RESULTS: For the 9 left-sided patients, the mean percentage of heart
      receiving more than 30 Gy (heart V30) was lower with the 5-field wedged technique
      than with the DT wedged technique (6.8% and 19.1%, respectively, p < 0.004). For
      the DT technique, the replacement of wedges with IMRT slightly diminished the
      mean heart V30 to 16.3% (p < 0.51). The introduction of mDIBH to the DT-IMRT
      technique reduced the heart V30 by 81% to a mean of 3.1% (p < 0.0004). Compared
      with 5-field IMRT, DT-IMRT with mDIBH reduced the heart V30 for 6 of the 9
      patients, entirely avoiding heart irradiation in 2 of these 6 patients. For DT
      IMRT, mDIBH reduced the mean lung dose and NTCP to levels obtained with the 5
      field IMRT technique. For the 15 patients planned with DT-IMRT in FB, the use of
      mDIBH reduced the mean percentage of both lungs receiving more than 20 Gy from
      20.4% to 15.2% (p < 0.00007). With DT-IMRT, more than 5% of the contralateral
      breast received more than 10 Gy for 6 of the 9 left-sided patients in FB, 3 of
      those 9 patients in mDIBH, and only 1 of those 9 patients planned with 5 fields.
      The mean % of the PTV receiving more than 55 Gy (110% of the prescribed dose) was
      36.4% for 5-field wedges, 33.4% for 5-field IMRT, 28.7% for DT-wedges, 12.5% for
      DT-IMRT, and 18.4% for DT-IMRT mDIBH. The CTV remained covered by the 95% isodose
      in all the DT plans but one (99.1% of the volume covered). DT-wedges required
      more MUs than DT-IMRT (mean of 645 and 416, respectively, p < 0.00004).
      CONCLUSION: mDIBH significantly reduces heart and lung doses when DT are used for
      LR breast irradiation including the IMNs. Compared with shallow tangents matched
      with electrons, DT with mDIBH reduces the heart dose (in most patients) and
      results in comparable lung toxicity parameters, but may increase the dose to the
      contralateral breast. IMRT improves dose homogeneity, slightly reduces the dose
      to the heart, and diminishes the number of MUs required.

PMID- 12527054
TI  - Clinical use of the hyperthermia treatment planning system HyperPlan to predict
      effectiveness and toxicity.
AB  - PURPOSE: The main aim is to prove the clinical practicability of the hyperthermia
      treatment planning system HyperPlan on a beta-test level. Data and observations
      obtained from clinical hyperthermia are compared with the numeric methods FE
      (finite element) and FDTD (finite difference time domain), respectively. METHODS
      AND MATERIALS: The planning system HyperPlan is built on top of the modular,
      object-oriented platform for visualization and model generation AMIRA. This
      system already contains powerful algorithms for image processing, geometric
      modeling, and three-dimensional graphics display. A number of hyperthermia
      specific modules are provided, enabling the creation of three-dimensional
      tetrahedral patient models suitable for treatment planning. Two numeric methods,
      FE and FDTD, are implemented in HyperPlan for solving Maxwell's equations. Both
      methods base their calculations on segmented (contour based) CT or MR image data.
      A tetrahedral grid is generated from the segmented tissue boundaries, consisting
      of approximately 80,000 tetrahedrons per patient. The FE method necessitates,
      primarily, this tetrahedral grid for the calculation of the E-field. The FDTD
      method, on the other hand, calculates the E-field on a cubical grid, but also
      requires a tetrahedral grid for correction at electrical interfaces. In both
      methods, temperature distributions are calculated on the tetrahedral grid by
      solving the bioheat transfer equation with the FE method. Segmentation, grid
      generation, E-field, and temperature calculation can be carried out in clinical
      practice at an acceptable time expenditure of about 1-2 days. RESULTS: All 30
      patients we analyzed with cervical, rectal, and prostate carcinoma exhibit a good
      correlation between the model calculations and the attained clinical data
      regarding acute toxicity (hot spots), prediction of easy-to-heat or difficult-to
      heat patients, and the dependency on various other individual parameters. We
      could show sufficient agreement between the calculations and measurements for
      power density (specific absorption rate) within the range of assessed precision.
      Tumor temperatures can only be estimated, because of the rather variable
      perfusion conditions. The results of the FE and FDTD methods are comparable,
      although slight differences exist resulting from the differences in the
      underlying models. There are also statistically provable differences among the
      tumor entities regarding the attained specific absorption rate, temperatures, and
      volume loads in normal tissue. However, gross fluctuations exist from patient to
      patient. CONCLUSION: The hyperthermia planning system HyperPlan could be
      validated for a number of the 30 patients. Further improvements in the
      implemented models, FE and FDTD, are required. Even at its present state of
      development, hyperthermia planning for regional hyperthermia delivers valuable
      information, not only for clinical practice, but also for further technologic
      improvements.

PMID- 12527055
TI  - Plug pattern optimization for gamma knife radiosurgery treatment planning.
AB  - PURPOSE: To develop a novel dose optimization algorithm for improving the sparing
      of critical structures during gamma knife radiosurgery by shaping the plug
      pattern of each individual shot. METHOD AND MATERIALS: We first use a geometric
      information (medial axis) aided guided evolutionary simulated annealing (GESA)
      optimization algorithm to determine the number of shots and isocenter location,
      size, and weight of each shot. Then we create a plug quality score system that
      checks the dose contribution to the volume of interest by each plug in the
      treatment plan. A positive score implies that the corresponding source could be
      open to improve tumor coverage, whereas a negative score means the source could
      be blocked for the purpose of sparing normal and critical structures. The plug
      pattern is then optimized via the GESA algorithm that is integrated with this
      score system. Weight and position of each shot are also tuned in this procedure.
      RESULTS: An acoustic tumor case is used to evaluate our algorithm. Compared to
      the treatment plan generated without plug patterns, adding an optimized plug
      pattern into the treatment planning process boosts tumor coverage index from
      95.1% to 97.2%, reduces RTOG conformity index from 1.279 to 1.167, lowers
      Paddick's index from 1.34 to 1.20, and trims the critical structure receiving
      more than 30% maximum dose from 16 mm(3) to 6 mm(3). CONCLUSIONS: Automated GESA
      based plug pattern optimization of gamma knife radiosurgery frees the treatment
      planning team from the manual forward planning procedure and provides an optimal
      treatment plan.

PMID- 12527056
TI  - A new irradiation unit constructed of self-moving gantry-CT and linac.
AB  - PURPOSE: To improve reproducibility in stereotactic irradiation (STI) without
      using noninvasive immobilization devices or body frames, we have developed an
      integrated computed tomography (CT)-linac irradiation system connecting CT
      scanner and linac via a common treatment couch. METHODS AND MATERIALS: This
      system consists of a linac, a CT scanner, and a common treatment couch. The linac
      and the CT gantry are positioned on opposite ends of the couch so that, by
      rotating the treatment couch, linac radiotherapy or CT scanning can be performed.
      The rotational axis of the linac gantry is coaxial with that of the CT gantry,
      and the position of the linac isocenter on the couch matches the origin of the
      coordinate system for CT scanning when the couch is rotated 180 degrees toward
      the CT side. Instead of the couch moving into the gantry, as in conventional CT,
      in this case the table is fixed and scanning is accomplished by moving the
      gantry. We evaluated the rotational accuracy of the common couch and the scan
      position accuracy of the self-moving gantry CT. RESULTS: The positional accuracy
      of the common couch was 0.20, 0.18, and 0.39 mm in the lateral, longitudinal, and
      vertical directions, respectively. The scan-position accuracy of the CT gantry
      was less than 0.4 mm in the lateral, longitudinal, and vertical directions.
      CONCLUSION: This irradiation system has a high accuracy and is useful for
      noninvasive STI and for verification of the position of a target in three
      dimensional conformal radiotherapy.

PMID- 12527057
TI  - Abstracts of the 2nd International Conference on Translational Research and
      Preclinical Strategies in Radiation Oncology. ICTR 2003. March 16-19, 2003.
      Lugano, Switzerland.

PMID- 12527058
TI  - Repeatability and accuracy of reproductive tract scoring to determine pubertal
      status in beef heifers.
AB  - The objective of this study was to compare the repeatability and accuracy of
      palpation per rectum to transrectal ultrasonography and serum progesterone
      concentrations for determining pubertal status in beef heifers. One hundred and
      seventy-four rectal examinations were performed on 29 predominantly Angus heifers
      by two veterinarians (A and B) and assigned individual reproductive tract scores
      (RTS) during monthly examinations over a 3-month period. Heifers were examined in
      the morning by both veterinarians, randomized, and re-examined in the afternoon.
      The size and location of ovarian structures of each heifer were determined by
      ultrasonography. Heifers with follicles >10mm in diameter or corpora lutea were
      classified as pubertal. Serum progesterone concentrations at the time of the
      examination and 10 days later were determined by radioimmunoassay and used to
      classify heifers as prepubertal (<1 ng/ml in both samples) or pubertal (at least
      one sample >or=1 ng/ml). Kappa, which describes degree of agreement beyond
      chance, was used to determine repeatability of the RTS system. Multicategory
      Kappa for agreement was 0.64 within veterinarian, 0.46 between veterinarian, and
      0.35 between palpation per rectum and transrectal ultrasonography. Sensitivity
      and specificity of palpation per rectum for diagnosis of pubertal status compared
      to serum progesterone levels were higher (82 and 69%, respectively) than
      sensitivity and specificity of ultrasonography (79 and 59%, respectively). This
      study validates the RTS system as a repeatable and accurate screening test to
      evaluate pubertal status in groups of heifers prior to the onset of the breeding
      season.

PMID- 12527059
TI  - In vitro survival of bovine spermatozoa stored at room temperature under
      epididymal conditions.
AB  - In this study, environmental conditions mimicking those prevailing in the
      epididymis were used for storing ejaculated bull spermatozoa in vitro during 4
      days at ambient temperature. These conditions were low pH, high osmolarity, high
      sperm concentration and low oxygen tension. Hepes-TALP was used as basic storage
      medium. Fresh spermatozoa were stored at a concentration of 10 x
      10(6)spermatozoa/ml in Hepes-TALP of different pH (pH 4, 5, 6, 7 or 8), and
      osmolarity (100, 300, 400, 500, 600 or 800 mOsm/kg), and under different
      atmospheric conditions (nitrogen gassed or aerobic). Spermatozoa were also stored
      undiluted or at different concentrations: 10x 10(6), 100 x 10(6), 500 x 10(6) or
      1 x 10(9)spermatozoa/ml. Sperm parameters such as membrane integrity, motility,
      mitochondrial membrane potential or DNA fragmentation were used to assess semen
      quality after storage. Adjustment of the pH of Hepes-TALP to pH 6 yielded
      significantly better results than storage at all other pH values. Isotonic Hepes
      TALP (300 mOsm/kg) had a less detrimental effect on spermatozoa than hypo- and
      hyperosmotic versions. No differences in sperm parameters were observed when
      spermatozoa were incubated under aerobic or under nitrogen gassed storage
      conditions. Optimal sperm concentration in vitro is 10 x 10(6)spermatozoa/ml.
      This is in contrast with the in vivo situation, where spermatozoa are stored at
      high concentration. However, better results at high sperm concentrations were
      obtained when spermatozoa were diluted for less than 5 min in Triladyl-egg yolk
      glycerol diluent immediately after ejaculation.

PMID- 12527060
TI  - Effect of sperm coating on the survival and penetrating ability of in vitro
      stored bovine spermatozoa.
AB  - The aim of this study was to examine the effect of sperm coating on the survival
      and penetrating ability of in vitro stored diluted spermatozoa. Bovine semen was
      collected by means of an artificial vagina connected with a tube containing 5 ml
      of the commercial Triladyl diluent supplemented with 20% egg yolk and 6.7%
      glycerol (EYTG). Both EYTG and seminal plasma were removed by centrifugation and
      the spermatozoa were stored under different in vitro storage conditions. In the
      first and second experiment, "control" and "coated" spermatozoa were stored in
      Hepes-TALP (pH 6 and 7) at room temperature. After 4 days of storage, the
      progressive motility, membrane integrity, mitochondrial membrane potential or DNA
      integrity of the spermatozoa were evaluated before and after Percoll
      centrifugation. The in vitro penetration rate of the spermatozoa was examined
      only after Percoll centrifugation. A significantly (P<0.05) positive influence of
      sperm coating was observed on the tested sperm characteristics and penetration
      rate of spermatozoa when they were stored in Hepes-TALP at pH 7, but not at pH 6.
      In the last experiment, the influence of the storage medium Hepes-TALP (pH 7) or
      EYTG was investigated on motility, membrane integrity, mitochondrial membrane
      potential and in vitro penetration potential of "coated" spermatozoa stored at
      room temperature or at 4 degrees C during 4, 5 and 6 days. After 6 days of
      storage, a significantly (P<0.05) higher percentage of motile and membrane intact
      spermatozoa with high mitochondrial membrane potential was obtained in EYTG at
      both temperatures leading to a significantly higher in vitro penetration rate.
      These results indicate that sperm coating could preserve sperm characteristics
      and penetrating capacity of fresh bovine spermatozoa stored in egg yolk
      containing diluent for up to 6 days.

PMID- 12527061
TI  - Bovine and buffalo in vitro embryo production using oocytes derived from abattoir
      ovaries or collected by transvaginal follicle aspiration.
AB  - This study was undertaken in order to evaluate the effect of oocyte source (live
      animals and abattoir ovaries) on subsequent embryo development in buffalo
      (Bubalus bubalis). Cow ovaries were also collected as oocyte donors for in vitro
      embryo production (IVEP). Three hundred thirty-eight oocytes were recovered by
      ovum pick up (OPU, Group A) from 8 pluriparous buffalo cows, while 1127 and 1457
      oocytes were aspirated, respectively, from buffalo (Group B) and bovine (Group C)
      slaughterhouse ovaries. Cumulus enclosed oocytes (COCs) suitable for IVEP were in
      vitro matured (IVM), fertilized (IVF) and cultured (IVC) to the tight morula (Tm)
      and blastocyst (Bl) stage. Within buffalo species Group A had a higher Bl yield
      (29.7 % versus 19.9%; P<0.05) and a lower proportion of embryos arrested at Tm
      stage (11.1% versus 22.3%; P<0.05) than Group B. Within slaughterhouse groups
      cattle oocytes had a higher cleavage rate (83.9% versus 64.8%; P<0.05) and
      yielded 49.2% more blastocysts than buffalo. However, when data are related to
      the total number of cleaved oocytes, only 13.7% more blastocysts were produced in
      cattle than in buffalo.In conclusion, in buffalo species the source of oocytes
      significantly affected post-fertilization embryo development, as demonstrated by
      the higher Bl yields derived from OPU-derived oocytes.A higher overall IVEP
      efficiency, mainly related to the higher cleavage rate, was recorded in cattle
      compared with buffalo when ovaries from an abattoir were used as oocyte donors.

PMID- 12527062
TI  - Pregnancy-associated glycoprotein concentrations during pregnancy and the
      postpartum period in Azawak Zebu cattle.
AB  - Specific RIA systems were developed and used to measure pregnancy-associated
      glycoprotein (PAG) concentrations during gestation and the postpartum period in
      Azawak Zebu cows. Twelve females were palpated per rectum and diagnosed as
      pregnant. Blood samples were taken at 5-10-day intervals from approximately Week
      8 of gestation until Week 10 postpartum (pp). One Zebu cow (Z15) initially
      diagnosed as pregnant showed PAG concentrations lower than the assay sensitivity
      (<0.20 ng/ml) and did not calve. Another cow (ZSand) showed abnormally high PAG
      concentrations during gestation and was excluded from the general PAG profile.
      The 10 other Zebu cows exhibited a very similar PAG profile. In these animals,
      concentrations increased progressively from Week 8 to 35 of gestation (from 6.0+/
      4.2 to 196.0+/-34.8 ng/ml), remaining relatively constant until Week 39 (210.8+/
      74.8 ng/ml), when they increased sharply to reach their highest level (1095.6+/
      607.2 ng/ml) at around parturition. After delivery, PAG concentrations declined
      significantly (P<0.05) until Week 2 postpartum (348.4+/-85.6 ng/ml) and slowly
      until Week 10 postpartum. Our results revealed that the PAG pattern in Zebu
      cattle was similar to those of taurine breeds during the first two trimesters of
      pregnancy, but differed in the peripartum period.

PMID- 12527063
TI  - Intracytoplasmic sperm injection of bovine oocytes with stallion spermatozoa.
AB  - Five experiments were designed to study the fertilizability and development of
      bovine oocytes fertilized by intracytoplasmic sperm injection (ICSI) with
      stallion spermatozoa. Experiment 1 determined the time required for pronuclear
      formation after ICSI. Equine sperm head decondensation began 3 h after ICSI; 42%
      were decondensed 6 h after ICSI. Male pronuclei (MPN) began to form 12 h after
      ICSI. Female pronuclei (FPN), however, formed as early as 6 h after ICSI. In
      Experiment 2, ionomycin, ionomycin plus 6-dimethylaminopurine (DMAP), and
      thimerosal were used to activate ICSI ova. None of the ICSI ova cleaved after
      treatment with thimerosal. Ionomycin activation after 24 and 30 h of oocyte
      maturation resulted in 29 and 48% cleavage rates, respectively. Ionomycin
      combined with DMAP resulted in 49, 6 and 3% cleavage, morula and blastocyst
      rates, respectively, when oocytes were activated after 24 h maturation. In
      Experiment 3, rates of cleavage (45-60%) and development to morulae (4-13%) and
      blastocysts (1-5%) stages following ICSI were not different (P>0.05) among three
      stallions. Treatment of stallion spermatozoa with ionomycin did not affect
      cleavage or development of ova fertilized by ICSI. The chromosomal constitution
      of blastocysts derived from ICSI was bovine, not bovine and equine hybrids. In
      Experiment 4, to make male and FPN form synchronously, colchicine and DMAP were
      used for 4 h to inhibit oocytes at metaphase during activation; 63% of oocytes
      were still at metaphase 8h after ICSI when treated with colchicine, and 50% of
      sperm nuclei were decondensed. About 18 h after ICSI, 21 and 50% male and FPN had
      formed, respectively, but cleavage rates were low, and only 1% developed to
      morulae. In Experiment 5, to test if capacitated equine sperm could fuse with the
      bovine oolemma, capacitated spermatozoa were injected subzonally (SUZI). Of the
      182 SUZI oocytes, 49 (27%) contained extruded second polar bodies. After
      activation of oocytes with second polar bodies, 44, 22 and 15% developed to 2-, 4
      and 8-cell stages, respectively, but development stopped at the 8-cell stage.
      None of the unactivated oocytes cleaved. In conclusion, equine spermatozoa can
      decondense and form MPN in bovine oocytes after ICSI, but subsequent embryonic
      development is parthenogenetic with only bovine chromosomes being found.

PMID- 12527064
TI  - Fertility of ram semen frozen in Bioexcell and used for cervical artificial
      insemination.
AB  - The current use of ingredients of animal origin, such as egg yolk, in semen
      extenders presents a risk of microbial contamination, and has led to the search
      for alternatives. Such an extender is commercially available for bull semen
      (Bioexcell), IMV, L'Aigle, France), and it has previously been tested in vitro
      for freezing ram semen, with satisfactory results. The aim of the present study
      was to compare the fertility results of ewes in Uruguay, after cervical
      insemination with ram semen that was frozen in Bioexcell versus semen frozen in a
      conventional milk-egg yolk extender (control). Semen from five Corriedale rams
      was frozen, using a split sample design, in either milk-egg yolk or Bioexcell
      extender, using a two-step extension method. The sperm parameters assessed after
      thawing were subjective motility, membrane integrity (SYBR-14/PI), and
      capacitation status (CTC). Thawed semen was inseminated intracervically once
      during spontaneous estrus in 970 Corriedale ewes that grazed in natural pastures,
      under extensive management conditions. Fertility was recorded as nonreturn rates
      at 21 days (NRR-21) and 36 days (NRR-36) after artificial insemination (AI), as
      well as pregnancy rate (PR-US, diagnosed ultrasonographically 50 days after AI of
      the last ewe). Subjective motility was slightly higher in Bioexcell than in the
      milk extender (47 vs. 46.5%; NS), as was membrane integrity (38 vs. 37.7%; NS)
      and the percentage of uncapacitated spermatozoa (28.5 vs. 26.3%; NS). There were
      no statistically significant differences in fertility rates found between
      Bioexcell and the control extender: NRR-21 (35.9 vs. 33.2%), NRR-36 (34.8 vs.
      32.6%), and PR-US (28.4 vs. 27.2%). In conclusion, Bioexcell appears to be an
      alternative to the conventional milk-egg yolk extender for freezing ram semen,
      and provides similar fertility results after cervical AI under extensive
      management conditions. Thus, Bioexcell, containing no additives of animal origin,
      can offer a safer alternative when frozen semen is used for introducing new
      genetic material into a flock or a country.

PMID- 12527065
TI  - Changes in the distribution of lectin receptors during capacitation and acrosome
      reaction in boar spermatozoa.
AB  - Sperm glycocalyx modifications are known to occur during capacitation and the
      acrosome reaction (AR). These changes are very important for gamete recognition
      and fertilization in mammals but are not fully understood. The purpose of this
      study was to determine the distribution of surface carbohydrates in boar
      spermatozoa during capacitation and the AR. These processes may be associated
      with specific changes in the content and distribution of surface carbohydrates.
      Thirty-nine ejaculates from fertile boars of various breeds were analyzed. N
      Acetylglucosamine and sialic acid, mannose and fucose residues were detected by
      fluorescence microscopy and flow cytometry using FITC-conjugated lectins.
      Triticum vulgaris agglutinin (WGA) bound on the head and tail of fresh sperm, and
      fluorescence intensity (FI) decreased in capacitated sperm (6751 to 5621
      fluorescence units (FU), P<0.05), and decreased further in acrosome-reacted sperm
      (5240 FU, P<0.05). Concanavalia ensiformis agglutinin (Con-A) bound homogeneously
      on the head and the midpiece of fresh sperm with a FI of 5335 FU, and increased
      in capacitated sperm (5957 FU, P<0.05) mainly on the acrosomal region. In
      acrosome-reacted sperm, fluorescence was concentrated on the border of the
      acrosomal region (5608 FU, P<0.05). It was not possible to detect Ulex europaeus
      agglutinin (UEA) by fluorescence microscopy. However, flow cytometry revealed UEA
      receptors (187 FU), with a nonsignificant decreased number in capacitated (142
      FU) and AR sperm (142 FU). Labeling patterns were similar in all breeds. Sperm
      glycocalyx modifications observed in this study provide insights to the molecular
      modifications accompanying capacitation and the AR. This kind of study could
      improve the diagnosis of reproductive problems of subfertile boars and males of
      other species.

PMID- 12527066
TI  - Association of uterine edema with follicle waves around the onset of the breeding
      season in pony mares.
AB  - During spring transition, when estrus may be exhibited for prolonged periods, it
      is important for veterinarians and stud farm personnel to be able to predict
      whether a large follicle will ovulate or regress. It is thought that the presence
      of ultrasonically detectable uterine edema indicates that a follicle will
      ovulate, however, there is little evidence to support this. In the present study,
      16 mares were regularly examined by transrectal ultrasonography to follow growth
      and regression of follicles from seasonal anestrus in February until second
      ovulation. Blood samples were collected daily for measurement of estradiol
      concentrations when a large ovarian follicle was present. Estrous-like uterine
      edema was detected during 7 of 11 (64%) anovulatory follicle waves, in 12 of 14
      (86%) mares before their first ovulation, and in 100% of mares before their
      second ovulation. Uterine edema was first detected 43+/-6.7 days before first
      ovulation. Large anovulatory follicles tended to be present for longer periods of
      time than ovulatory follicles. Uterine edema was present for a significantly
      greater proportion of time in the presence of a large follicle at second
      ovulation than at first ovulation (P<0.05) or for anovulatory follicles (P<0.01).
      Peak plasma estradiol concentrations and mean plasma estradiol concentrations
      were significantly higher (P<0.001) when a dominant preovulatory follicle was
      present compared with a dominant anovulatory follicle, but there was no
      difference in estradiol concentrations between first and second ovulations. It
      was apparent, therefore, that uterine edema was not a reliable indicator of
      follicular steroidogenic competence, or of whether the follicle would ovulate.

PMID- 12527067
TI  - Sephadex and sephadex ion-exchange filtration improves the quality and
      freezability of low-grade buffalo semen ejaculates.
AB  - The effect of sephadex and sephadex ion-exchange filtration on the improvement in
      quality and freezability of low-grade buffalo semen ejaculates was assessed. Two
      types of filtration columns were used: one containing only sephadex G-10 (FS) and
      the other sephadex G-10 along with ion-exchangers (diethyl amino ethane-52 (DEAE
      52) cellulose and carboxy methyl-52 (CM-52) cellulose; FS+IE). Unfiltered samples
      served as controls. Semen ejaculates extended in Tris-citric acid (1:4) (n=16;
      initial motility 40-50%) were filtered at the rate of 1.5 ml/min under negative
      pressure at room temperature (28-30 degrees C). The mean recovery rate (%) of
      motile spermatozoa in the FS (85.9+/-1.51) and FS+IE (77.10+/-2.28) filtrates did
      not differ significantly. Percentages of sperm motility, normal acrosomes, and
      intact plasma membranes were highest (P<0.05) in FS+IE, intermediate (P<0.05) in
      FS and lowest (P<0.05) in controls at the three stages of cryopreservation
      (postfiltration final dilution, after equilibration, and after freezing). Mean
      sperm abnormalities were lowest (P<0.05) in the filtrates of FS+IE, moderate
      (P<0.05) in FS and highest in controls at all stages of freezing. Compared to
      dilution and equilibration, freezing greatly reduced (P<0.05) the overall percent
      motility, normal acrosomes and intact plasma membranes. The spermatozoa eluted
      through FS+IE columns proved more resistant (P<0.05) in bearing dilution,
      equilibration, freezing and thawing stresses than the spermatozoa from FS and
      control samples. It is concluded that filtration systems containing an FS+IE
      column can effectively enhance the quality and freezability of extended, low
      quality buffalo semen.

PMID- 12527068
TI  - Estrus induction following PGF2alpha treatment in the superovulated buffalo
      (Bubalus bubalis).
AB  - Early return-to-estrus after embryo collection would shorten the interval between
      consecutive superovulations and improve efficiency of embryo production.
      Following superovulation and embryo collection, 80 buffaloes were treated with
      15.0mg Luprostiol (PGF2alpha analogue) for the induction of luteolysis and early
      return-to-estrus. A total of 67.5% donor animals returned to estrus, on average
      11.8+/-0.84 days after the PGF2alpha treatment. The number of ovulations (<or=5
      or >5 CL) had no significant effect on the percentage of donors returning to
      estrus within 30 days, as 70% of the buffaloes with <or=5 CL and 65% with >5 CL
      returned to estrus during this time. However, an increase in the number of
      ovulations significantly delayed the return to estrus as this duration was 9.7+/
      0.93 days in the buffaloes with <or=5 CL compared to 14.1+/-1.29 days in those
      having >5 CL.

PMID- 12527069
TI  - New technology for vitrification and field (microscope-free) warming and transfer
      of small ruminant embryos.
AB  - This study was designed to test the efficiency of recently developed
      vitrification technology followed by microscope-free thawing and transfer of
      sheep embryos. In a first set of experiments, in vivo derived embryos at the
      morula to blastocyst stage were frozen in an automated freezer in ethylene
      glycol, and after thawing and removal of cryoprotectants, were transferred to
      recipient ewes according to a standard protocol (control group). A second group
      of embryos were loaded into open-pulled straws (OPS) and plunged into liquid
      nitrogen after exposure at room temperature to the media: 10% glycerol (G) for 5
      min, 10% G+20% ethylene glycol (EG) for 5 min, 25% G+25% EG for 30s; or 10%
      EG+10% DMSO for 3 min, 20% EG+20% DMSO+0.3M trehalose for 30s. The OPS were
      thawed by plunging into tubes containing 0.5M trehalose. After this rapid
      thawing, the embryos were directly transferred using OPS as the catheter for the
      transplantation process. In a second set of experiments, in vivo derived and in
      vitro produced expanded blastocysts were vitrified in OPS and then transferred as
      described above. The lambing rates recorded (59% for the conventionally
      cryopreserved in vivo derived embryos, 56% for the vitrified in vivo derived
      embryos, and 20% for the vitrified in vitro produced embryos), suggest the
      suitability of the vitrification technique for the transfer of embryos obtained
      both in vivo and in vitro. This simple technology gives rise to a high embryo
      survival rate and will no doubt have applications in rearing sheep or other small
      ruminants.

PMID- 12527070
TI  - Effects of gas conditions, time of medium change, and ratio of medium to embryo
      on in vitro development of horse oocytes fertilized by intracytoplasmic sperm
      injection.
AB  - This study was conducted to evaluate the effects of two different gas conditions
      (5% CO(2) in air or 5% CO(2), 5% O(2), 90% N(2), mixed gas), time of medium
      change (Day 3 or 4) and ratio of medium to embryo (2, 5 or 10 microl per
      presumptive zygote) on the development of horse oocytes fertilized by
      intracytoplasmic sperm injection and cultured in G1.2/2.2 medium. Oocytes from
      slaughterhouse-derived ovaries were matured in vitro for 24 h and fertilized by
      injection of frozen-thawed sperm using micromanipulation with a Piezo drill.
      Presumptive zygotes were randomly assigned to 5% CO(2) in air or mixed gas and
      fixed after 96 h of culture. Cleavage rates between two gas conditions were
      similar (67 and 63%), but the mean nucleus number of embryos in the mixed gas
      treatment was significantly (P<0.05) higher than that of embryos cultured in 5%
      CO(2) in air (15.2 versus 7.0, respectively). Further experiments were done with
      mixed gas incubation. Development of embryos was compared after change from G1.2
      to G2.2 medium at Day 3 or 4. There was no significant difference in cleavage
      rate (56 and 65%, respectively) or development to the blastocyst stage after 7
      days of culture (5% and 46%, respectively) between embryos changed on different
      days. To evaluate the effect of the ratio of medium to embryo, zygotes were
      cultured at a ratio of 2, 5 or 10 microl medium per zygote. There were no
      significant differences among ratio treatments in rates of cleavage or
      development to blastocyst.

PMID- 12527071
TI  - Development of bovine oocytes reconstructed with a nucleus from growing stage
      oocytes after fertilization in vitro.
AB  - The developmental capacity of reconstructed bovine oocytes that contained nuclei
      from growing stage oocytes, 70-119 microm in diameter, was assessed after
      fertilization in vitro. Nuclei from growing stage oocytes of adult ovaries were
      transferred to enucleated, fully grown germinal vesicle (GV) stage oocytes. After
      culture in vitro, the reconstructed oocytes matured, forming the first polar body
      and MII plate. To supply the ability to form pronuclei, the resultant MII plate
      was transferred to enucleated MII oocytes, which were obtained by in vitro
      culture of cumulus-oocyte complexes. After fertilization in vitro, 11-15% of the
      reconstructed oocytes developed to morulae and blastocysts. To assess the ability
      to develop to term, a total of 27 late morulae and blastocysts were transferred
      to 19 recipient cows. Of the three cows that subsequently became pregnant, one
      recipient, who received two embryos derived from reconstructed oocytes with a
      nucleus from oocytes 100 to 109 microm in diameter, continued the pregnancy to
      Day 278 of gestation. This pregnancy, however, was unexpectedly a triplet
      pregnancy that included a set of identical twins and resulted in the premature
      birth of the calves, followed by death from lack of post-parturient treatment.
      These results show that bovine oocyte genomes are capable of supporting term
      development before the oocytes grow to their full size, which suggests that
      growing stage oocytes can be directly used as a source of maternal genomes.

PMID- 12527073
TI  - Serum-free culture of murine primordial germ cells and embryonic germ cells.
AB  - Fetal calf serum (FCS) has usually been used for culture of embryonic stem (ES)
      cell as a component of the culture medium. However, FCS contains undefined
      factors, which promote cell proliferation and occasionally stimulate
      differentiation of ES cells. Recently, a chemically-defined serum replacement,
      Knockout Serum Replacement (KSR), was developed to maintain ES cells in an
      undifferentiated state. In this experiment, we examined the effects of KSR on the
      growth and differentiation of primordial germ cells (PGCs) and embryonic germ
      (EG) cells. PGCs were collected 8.5 days postcoitum (dpc) from B6D2F1
      (C57BL/6JxDBA/2J) female mice mated with B6D2F1 males. Most of the PGCs that were
      cultured in FCS-supplemented medium (FCS medium) had alkaline phosphatase (AP)
      activity and acquired a fibroblast cell shape. In contrast, PGCs in KSR
      supplemented medium (KSR medium) proliferated, maintaining round and stem cell
      like morphology. In addition, EG cells were established more easily from PGCs
      cultured in KSR medium than from PGCs cultured in FCS medium. The percentage of
      undifferentiated colonies of EG cells was significantly higher in KSR medium than
      in FCS medium. The germ line chimera was also produced from EG cells established
      in KSR medium. These results suggest that KSR can be used for sustaining an
      undifferentiated state of PGCs and EG cells in vitro.

PMID- 12527072
TI  - Influence of extender, temperature, and addition of glycerol on post-thaw sperm
      parameters in ram semen.
AB  - Using a two-step extension methodology, two experiments were conducted using a
      split-sample design to compare the effect on post-thaw ram sperm parameters of a
      milk-based extender (Experiment 1) containing four different egg yolk
      concentrations (5% [M5], 10% [M10], 15% [M15], and 20% [M20]), and a commercially
      available extender (Bioexcell); IMV, L'Aigle, France) free from additives of
      animal origin, containing two different final glycerol concentrations (3.2% [B]
      and 6.4% [BB]) (Experiment 2). In both experiments, glycerol was added either at
      5 degrees C or at 15 degrees C together with the second fraction of each
      extender. The sperm characteristics assessed were motility (measured subjectively
      [SM] and by means of cell motion analysis (CASA), membrane integrity (SYBR
      14/PI), and capacitation status (chlortetracycline (CTC)/EthD-1). Results of
      Experiment 1 showed no significant positive effect of increasing the
      concentration of egg yolk above 10% on post-thaw motility, membrane integrity, or
      induction of sperm capacitation-like changes. In Experiment 2, Bioexcell (BB)
      yielded similar post-thaw results as did the milk extender (control). In both
      experiments, post-thaw sperm parameters were better preserved when glycerol was
      added at 5 degrees C, although the results were not always statistically
      significant for all variables studied. In conclusion, when using milk-based
      extenders for freezing ram semen, low (5-10%) concentrations of egg yolk and the
      addition of glycerol at 5 degrees C are recommended. Furthermore, the results
      indicate that when freezing ram semen, Bioexcell containing 6.4% glycerol may be
      used as an alternative extender to the conventional milk extender containing 5%
      egg yolk.

PMID- 12527074
TI  - Factors affecting the survival of sheep embryos after transfer within a MOET
      program.
AB  - Multiple ovulation and embryo transfer (MOET) has the potential to increase the
      rate of genetic improvement in sheep. However, better realization of this
      potential requires maximum survival rates of transferred embryos of high genetic
      merit after transfer into recipient ewes. These studies were therefore conducted
      to investigate the effect of both embryonic and recipient ewe factors on the
      survival rate of transferred embryos. Survival rate was similar after transfer of
      morula or blastocyst stage embryos, and these were higher (P<0.05) than for very
      early morulae and early morulae. Advanced embryos (Day 5 blastocyst) had an
      advantage (P<0.05) in survival rate over retarded embryos (Day 6 morula). Grades
      1 and 2 embryos survived significantly (P<0.05) better than Grades 3 or 4
      embryos. There was no difference in embryo survival rate following transfer to
      recipients with different numbers of corpora lutea. In general, age or parity of
      recipient ewes did not affect embryo survival rate, although a higher (P<0.05)
      embryo survival rate was observed for yearling recipients. Buserelin (GnRH
      agonist) treatment of recipient ewes 5 or 6 days after transfer of embryos (Day
      12 of the cycle) did not improve embryo survival rate. These results confirm that
      both embryonic and recipient factors can play an important role in the success of
      a MOET program in sheep.

PMID- 12527075
TI  - Studies of the cell cycle of in vitro cultured skin fibroblasts in goats: work in
      progress.
AB  - The effect of serum starvation and olomoucine treatment on the cell cycle and
      apoptosis of goat skin fibroblasts cultured in vitro is reported in this paper.
      The cells were obtained from the ear of a female goat 1.5 years of age. Analysis
      of cell cycle distribution by fluorescence-activated cell sorting (FACS) showed
      that 3.4, 60.8 and 15.1% of normally cycling cells were at G1, G0 and S phase,
      respectively. Serum starvation for 1, 3 and 5 days arrested 70.1, 70.2 and 83.4%
      cells, respectively, at G0/G1 phase. Seventy-eight percent of confluent cells
      were at G0/G1 stage, but in contrast to the serum starved group, this high
      percentage of G0/G1 cells was mainly associated with G1 cells. Of cells not
      deprived of serum, 73.6% were arrested at G1/G0 when treated with 100 microM
      olomoucine for 9 h compared to 85.5% of cells that had been starved of serum for
      2 days (co-inhibition) (P<0.01). After co-inhibition, 45% of cells entered S
      phase when re-cultured in normal medium for 5 h, indicating that the inhibition
      was reversible. Under normal culture conditions, 1.2% of cells underwent
      apoptosis. Serum starvation for 1, 2, 3, 5 and 10 days caused apoptosis in 1.7,
      3.9, 4.5, 11.7 and 90.3% of cells, respectively. Treatment with 100 microM
      olomoucine for 9h did not increase the number of apoptotic cells significantly
      (1.9%, P>0.05). When cells were co-inhibited, 4.1% of cells underwent apoptosis.
      In conclusion, although serum withdrawal for 5 days or more effectively arrested
      cells at G0/G1 stages, it increased apoptosis of cells significantly. However, co
      inhibition by serum withdrawal and olomoucine treatment was found to be an
      appropriate treatment to obtain more healthy G0/G1 cells based on the low
      percentage of apoptotic cells after treatment.

PMID- 12527076
TI  - Double radial immunodiffusion as a tool to identify pregnancy-associated
      glycoproteins in ruminant and nonruminant placentae.
AB  - Pregnancy-associated glycoproteins (PAGs) are antigens synthesized in the
      superficial layers of the ruminant trophoblast. Initially, they were identified
      either as proteins released into the maternal bloodstream (where they have
      applications in pregnancy diagnosis) (PAG1) or as molecules binding to the LH
      receptor (PAG2). In this study, double radial immunodiffusion was used to test
      the ability of antisera raised against different PAG molecules (bovine, ovine and
      caprine) to react with placental extracts from nonruminants (rabbit, cat, mouse,
      pig, and wild pig) and ruminants (cow, ewe, and goat). Placental extracts from
      all nonruminants tested except rabbit reacted with anti bovine PAG2 (anti
      boPAG2). Extracts of ruminant placentas reacted with different antisera,
      confirming the expression of various PAG molecules. According to the time at
      which the placentas were collected (early or middle pregnancy), the reaction
      differed as regards the thickness, position, and number of precipitation lines,
      suggesting that PAG expression varies as pregnancy progresses. Bos indicus and
      Bos taurus placental extracts exhibited different reactions with anti-boPAG2: a
      single precipitation line in the former case and two lines in the latter. This
      suggests differential expression of boPAG2 related glycoproteins in these two
      subspecies.

PMID- 12527077
TI  - Reproduction in female yaks (Bos grunniens) and opportunities for improvement.
AB  - This paper reviews seasonal breeding, puberty, postpartum anestrus, embryonic
      loss and calf survival and their constraints in female yaks. Methods for
      improving fertility in postpartum yak cows are also considered. Yaks are seasonal
      breeders with mating and conception restricted in the warm season. Puberty
      generally occurs in the 2nd to the 4th warm season following birth, i.e. between
      13 and 36 months of age. The cows usually have a long postpartum anestrus period;
      only a small proportion of the cows return to estrus in the 1st breeding season
      after calving, most come into estrus in the 2nd and 3rd years. Nutritional status
      is the most important determinant of reproduction in female yaks. Reproductive
      success is a direct result of the availability of pasture determined by climate,
      season, and management practices. Milking delays puberty by reducing milk intake
      (restricted suckling) and growth rate for the calf. Milking interferes with
      grazing and prolongs the duration of postpartum acyclicity in cows. Calves born
      early in the season have a longer suckling season than those born later in the
      season before the onset of winter. Thus, they can have their first cycle in the
      breeding season of the following year, while those born late in the season may
      not have their first estrus until 25 or 26 months of age. Cows calving early in
      the season are more likely to return to estrus in the year of calving because
      they have a longer period to recover from the demand on body reserves before the
      onset of winter. Inbreeding in smallholder yak farms is also discussed and
      minimizing inbreeding by exchanging bulls among different herds is suggested.
      Reproductive efficiency can be improved by nutritional supplementation during the
      winter, however, the most cost-effective and practical strategy for this needs to
      be determined. Early weaning or restricted suckling may shorten the duration of
      postpartum acyclicity, however, it is impractical due to reduced growth rates and
      increased winter mortality of early weaned calves. A single treatment with either
      GnRH, or PGF(2alpha)+GnRH can successfully induce estrus in yak cows that calved
      in previous years (with or without calf) but did not calve in the current year,
      however, it has little effect in cows nursing a calf born in the current year.
      The effects of administration of exogenous progestogens plus GnRH on the
      fertility of yak cows are worthy of further study.

PMID- 12527078
TI  - Impact of consuming tall fescue seeds infected with the endophytic fungus,
      Neotyphodium coenophialum, on reproduction of chickens.
AB  - Most of the 14 million hectares of pastures of tall fescue (Festuca arundinacea)
      planted in the United States are infected with the endophytic fungus,
      Neotyphodium coenophialum. I examined whether the consumption of fescue seed
      infected with this fungus had an adverse impact on reproduction in birds.
      Chickens were used as the model; they were maintained on a diet of chick starter
      mixed in equal amounts with either infected fescue seed (fungus-fed chickens) or
      uninfected fescue seed (control chickens). Consumption of infected fescue seed
      slowed the growth rates of female chicks but not males. Fungus-fed hens gained
      weight more slowly than control hens and also produced fewer eggs. Egg weight and
      fertility were similar in both groups of hens. Fungus-fed hens were more likely
      than control hens to produce eggs which lacked a shell. Naive hens exhibited an
      aversion for infected fescue seed when the seed was first presented to them, but
      the aversion disappeared after the hens were placed on a diet which included
      fescue seed for 3 or 6 months. Hens did not discriminate between feed containing
      infected seed and feed containing uninfected seed.

PMID- 12527079
TI  - Effect of probe location on changes in vaginal electrical impedance during the
      porcine estrous cycle.
AB  - The impedance technique is one of many methods that can be used for noninvasive
      monitoring of reproductive events occurring in cyclic animals. The influence of
      the depth of probe insertion on changes in vaginal impedance in sows during the
      estrous cycle was examined. Sows were checked twice a day for estrus via exposure
      to a sexually mature boar. The criterion for confirmation of ovulation was an
      increase in plasma progesterone levels above 4.0 ng/ml 8 and 12 days after the
      beginning of estrus. The impedance measurements were carried out using a four
      terminal method at a distance of 8, 10, 12, 14, 16 and 18 cm from the vulva. In
      all six locations of the vagina the mean impedance values decreased gradually
      after weaning (P<0.01), achieved a nadir 1-2 days before estrus and increased
      during estrus (P<0.01). It was found that the probe location within the vagina
      and the parity of sows significantly affected the impedance measured by means of
      a four-terminal method. The study suggests that the causes of impedance
      fluctuation are not only technical but also include a number of poorly understood
      biological causes.

PMID- 12527080
TI  - Effect of local interaction of reactive oxygen species with prostaglandin
      F(2alpha) on the release of progesterone in ovine corpora lutea in vivo.
AB  - Prostaglandin (PG) F(2alpha) is implicated in the process of luteal regression in
      many species, and has been shown to increase the generation of reactive oxygen
      species. In this study, the role of reactive oxygen species in the local
      regulatory mechanisms of functional luteolysis in the ewe was examined. In
      Experiment 1, we studied local effects of hydrogen peroxide (H(2)O(2)) and its
      interaction with PGF(2alpha) on P secretion in ovine corpus luteum (CL) in vivo.
      For this purpose, a microdialysis system (MDS) was used, where only the cells
      surrounding the capillary membrane in the microenvironment of the CL are exposed
      to these factors, and the P secretory ability of the CL is maintained as if
      intact. The study used a multiple CL model to implant the MDS, enabling us to
      examine in parallel several experimental infusions into the MDS implanted in
      different CLs (one MDS line per CL) developed after superovulation in one ewe. On
      Day 8 after GnRH treatment, the MDS were implanted into multiple CL in both
      ovaries of six ewes. A 4-h infusion with PGF(2alpha) (10(-6)M) at 8-12 h slightly
      increased P release during infusion, while a 4-h infusion with H(2)O(2) (10(-3)M)
      at 20-24 h decreased P release at 27-38 h. A pre-infusion with PGF(2alpha) for 4h
      at 8-12h, followed by infusion of H(2)O(2) at 20-24 h rapidly decreased the P
      release at 20-40 h (P<0.05); this decrease occurred 7h earlier than in the CL
      treated with H(2)O(2) alone. In Experiment 2, by utilizing the MDS we also
      applied free radical scavengers to examine their possible weakening effect on the
      inhibition of P secretion in the microenvironment within the regressing CL
      induced by PGF(2alpha) treatment. On Day 8 after estrus, the MDS were implanted
      into the CL (single CL model, two MDS lines per CL). Infusion of free radical
      scavengers, superoxide dismutase (SOD;50mg/ml)+catalase (CAT; 10mg/ml), at 0-28 h
      first increased P release until 12 h (P<0.05), and consequently delayed the
      decrease in P release until 30 h after administration of PGF(2alpha) i.m.
      (P<0.05). The present results support the concept that the leading pathway from
      PGF(2alpha) induces an increase of reactive oxygen species in luteolysis in the
      ewe.

PMID- 12527081
TI  - Screening of some variables influencing the results of embryo transfer in the
      ewe. Part II: two-day-old embryos.
AB  - Each of sixty Rasa aragonesa ewes received two embryos on Days 2-3 of the estrous
      cycle (Day 0=estrus) from 27 donors of the same breed that were superovulated
      with pFSH. The influence of several variables on fertility and prolificacy after
      transfer was studied by discriminant analysis. Our results showed that the main
      variables contributing to higher fertility were: in the donor-recipient couple,
      degree of estrus synchrony between them (better if donors were in estrus before
      recipients); in recipients, interval from FGA withdrawal to estrus onset,
      prolificacy in the previous lambing, age (all, better if inferior to the mean)
      and interval from the previous lambing (better if superior to the mean); in
      donors, ovulation rate (better if lower than the mean); and in embryos,
      developmental stage (better if superior to the mean). Likewise, the main
      variables contributing to higher prolificacy were: in donors, body condition
      score (better if higher than the mean) and weight (better if inferior to the
      mean); and in recipients, plasma progesterone concentration at transfer (better
      if inferior to the mean). The percentage of ewes correctly classified as lambing
      or not was 71.7% (P<0.01), and 72.5% of the ewes were correctly classified as
      having one or two lambs (P<0.05). Whether the criteria we have found for optimum
      results after transfer are applicable or not to conditions other than ours will
      need to be confirmed.

PMID- 12527082
TI  - The effect of intrauterine administration of estradiol on postpartum uterine
      involution in cattle.
AB  - In cattle, the first postpartum dominant follicle has a predilection for the
      ovary contralateral to the previously gravid uterine horn. However, the presence
      of an estradiol-secreting dominant follicle in the ipsilateral ovary is a marker
      of subsequent fertility, possibly due to a localized effect of ovarian estradiol
      on uterine involution. The present study tested the hypothesis that estradiol
      increases the rate of uterine involution when administered into the previously
      gravid uterine horn around the expected time of selection of the first postpartum
      dominant follicle. Dairy cows were treated with 10 mg estradiol benzoate (n=15)
      or saline (n=14) administered through the cervix into the previously gravid
      uterine horn lumen on Days 7 and 10 postpartum. Uterine involution was monitored
      by daily transrectal ultrasonography and estimation of peripheral plasma
      concentrations of PGFM and acute phase proteins, while ovarian function was
      monitored by ultrasonography and measurement of plasma hormone concentrations.
      There was no effect of estradiol treatment on the diameter of the previously
      gravid or nongravid uterine horns, nor on the plasma concentrations of PGFM or
      acute phase proteins. However, cows in which the first postpartum dominant
      follicle ovulated during the study period had a smaller diameter of the
      previously gravid (P<0.01) or nongravid uterine horns (P<0.001) compared with
      cows in which the follicle regressed. Thus, our hypothesis was not proven, and
      the opposite pathway of utero-ovarian signaling may be more important during the
      postpartum period.

PMID- 12527083
TI  - The effect of vitamins during maturation of caprine oocytes on subsequent
      developmental potential in vitro.
AB  - Only a small proportion of goat oocytes selected for in vitro oocyte maturation
      (IVM) can successfully complete cytoplasmic maturation and support embryonic
      development. To produce goat blastocysts more efficiently in vitro, it is
      necessary to identify factors required during oocyte maturation. The objective of
      this study was to determine the role of vitamins during maturation of caprine
      oocytes in semi-defined medium on subsequent developmental capacity in vitro.
      Cumulus oocyte complexes (COCs) collected from a local abattoir were matured in
      synthetic oviductal fluid (SOF) medium supplemented with BSA, LH, FSH, and EGF in
      the presence or absence of MEM vitamins for 24 h. The COCs were co-incubated with
      frozen-thawed sperm in Bracket and Oliphant fertilization medium for 18-22 h.
      Embryos were cultured in G1.2 medium for 72 h followed by culture in G2.2 medium
      for an additional 72 h. Addition of vitamins significantly increased (P<0.05)
      overall blastocyst development (16.4+/-1.2% versus 12.3+/-1.1%), and tended to
      increase (P<0.06) the percentage of cleaved embryos (61.4+/-3.0% versus 52.7+/
      2.6%). Addition of MEM vitamins to SOF maturation medium significantly increased
      (P<0.05) mean blastocyst cell number compared with control medium (107.7+/-6.0
      versus 85.1+/-6.3). Hatched blastocysts tended to have increased (P<0.06) cell
      numbers in the vitamin-treated group (150.5+/-8.4 versus 123.4+/-8.8). These
      results suggest that addition of vitamins during oocyte maturation is beneficial
      for subsequent blastocyst development and viability.

PMID- 12527084
TI  - Secretion patterns of oxytocin and PGF2alpha-metabolite in response to cervical
      dilatation in cyclic mares.
AB  - We conducted the present study to establish a standardized method for cervical
      stimulation without affecting the endometrium, and to investigate the effect on
      estrous cycle pattern and concentrations of progesterone, oxytocin and PGF2alpha
      metabolite of cervical dilatation in the mare. Six healthy Haflinger mares
      underwent three different treatments (control, insertion, dilatation) on Days 5
      and 7 of the cycles in different orders according to a Latin square design.
      During dilatation, the balloon of the catheter was inflated stepwise every 30s
      with warm physiological saline to a maximum of 50 ml. At this stage the size of
      the balloon was 4.5 cm in diameter and 6 cm length. Estrous cycle length was
      significantly shortened by dilatation when compared to controls (control: 22.8+/
      1.7, insertion: 21.8+/-2.5, dilatation: 20.0+/-1.3 days; P<0.05). Concentrations
      of progesterone at Days 10, 12 and 14 after ovulation were significantly lower in
      dilatation cycles. Calculation of the area under the curve (AUC) for progesterone
      secretion from Day 7 to Day 12 also revealed a significant decrease in
      progesterone secretion in the dilatation group (dilatation: 34.1+/-7.3,
      insertion: 35.6+/-7.8, control: 39.1+/-5.9 ng/ml; P<0.05). Cervical insertion and
      dilatation caused a rapid and pronounced increase in plasma concentrations of
      oxytocin from basal levels (1.0-6.1 pg/ml) to maximum peaks (insertion: 125.5
      pg/ml and dilatation: 305.2 pg/ml). The AUC for oxytocin was significantly higher
      after insertion (Day 5: 858.4+/-469.9; Day 7: 411.9+/-213 pg/ml/h) and dilatation
      (Day 5: 1697+/-1725; Day 7: 1078.5+/-764 pg/ml/h) when compared to controls (Day
      5: 186+/-98; Day 7: 156+/-23.5 pg/ml/h; P<0.05). Manipulations did not cause
      considerable changes in plasma PGF2alpha-metabolite concentrations. Because
      cervical dilatation up to a diameter of 4.5 cm did not cause any immediate
      PGF2alpha release, the luteolytic pathway is unlikely to be responsible for
      shortening the length of diestrus and the estrous cycle. The present data suggest
      an involvement of oxytocin in the shortening of the luteal phase in response to
      cervical manipulation.

PMID- 12527085
TI  - Growth factors and growth hormone enhance in vitro embryo production and post
      thaw survival of vitrified bovine blastocysts.
AB  - The objective of this study was to assess the influence of specific growth
      factors and growth hormone (GH) in the culture medium on in vitro embryo
      production and post-thaw survival of vitrified blastocysts. In total, 1673 bovine
      oocytes were used for evaluating the nuclear status of the oocytes after in vitro
      maturation (n=560) or for in vitro fertilization (IVF, n=1113) and distributed in
      five treatment groups: (1). medium only control; (2). activin (10 ng/ml); (3).
      epidermal growth factor (EGF) (10 ng/ml); (4). insulin 5 microg/ml and (5). GH
      (100 ng/ml). There was an increase (P<0.05 and P<0.01, respectively) in the
      percentage of oocytes that reached meta phase II, developed to blastocysts and
      hatched, as well as in the blastocyst cell number in the groups treated with
      activin, EGF and GH compared to controls. There was no significant difference
      between insulin and control groups. A total of 465 blastocysts were vitrified in
      a three-step protocol using ethylene glycol and polyvinylpyrrolidone. After
      thawing, embryos were cultured in five treatments groups as described above.
      Groups EGF and GH had higher (P<0.05) survival rates with a mean blastocyst
      survival of 95.0+/-1.5 and 93.1+/-3.5%, respectively, while mean hatching rate
      was higher for EGF and activin groups (75.3+/-3.4 and 62.0+/-3.2%, respectively).
      Thawed control blastocysts had a mean cell count of 52.7+/-3.3%. With the
      exception of insulin, all growth factors and GH tested showed higher (P<0.01)
      total cell numbers when compared to controls. In conclusion, addition of growth
      factors and GH in the culture media has favorable effects on in vitro maturation,
      in vitro embryo production, and post-thaw survival of vitrified blastocysts.

PMID- 12527086
TI  - Serum thyroid hormones and reproductive characteristics of Rambouillet ewe lambs
      treated with propylthiouracil before puberty.
AB  - Twenty-four Rambouillet ewe lambs (average weight=43.7+/-1.2 kg, approximately 6
      months of age) were used to examine the effect of thyroid suppression before the
      onset of puberty on serum thyroid hormones, body weights (BW), and reproductive
      performance. Beginning in early September, ewe lambs were randomly assigned to
      three treatments (n=8 lambs/treatment). All animals remained in a single pen (4 x
      12 m) with access to salt, water, shade and alfalfa hay (2.5 kg per animal per
      day) throughout the experiment. Beginning on Day 0 (first day of treatment), all
      ewe lambs received daily treatments (gavage) for 15 days consisting of 0, 20, or
      40 mg 6-N-propyl-2-thiouracil(PTU)/kg BW per day. Beginning on Day 15, the 20 and
      40 mg treatments were lowered to 10 and 20 mg PTU/kg BW, respectively. All
      animals were treated for 28 days. Ovarian cyclicity was determined by twice
      weekly progesterone (P(4)) analysis. Thyroxine (T(4)) concentrations were similar
      on Day 0 (61.6, 54.8 and 56.9+/-2.5 ng/ml, P=0.17) in ewe lambs receiving 0, 20
      and 40 mg PTU/kg BW, respectively. By Day 7, both PTU-treated groups had T(4)
      values less than 20 ng/ml (9.0 and 15.4+/-2.5 ng/ml) compared with 78.5 ng/ml in
      controls (P<0.01). By 7 days after termination of PTU treatment, serum T(4) had
      risen to 29.1 and 26.9 (+/-2.9)ng/ml in the 20/10 and 40/20 PTU groups,
      respectively. On Day 66, control ewes had 55.0 ng T(4)/ml compared with 43.1 and
      39.0 (+/-2.6 ng/ml) for ewes in the 20/10 and 40/20 groups, respectively (linear,
      P<0.01). Serum triiodothyronine (T(3)) followed a similar pattern to that
      observed for T(4). Ewe lamb BW were similar (P>0.50) among groups throughout the
      treatment period. However, following the treatment, PTU-treated ewes tended
      (P<0.10) to weigh less than controls. Average Julian day of puberty was also
      similar (P>0.50) among treatments (286, 288 and 288+/-5 days; control, 20/10 and
      40/20, respectively). Control ewes had a pregnancy rate of 75%, while both PTU
      treated groups had pregnancy rates of 88% (P>0.20). The administration of PTU
      resulted in a rapid decline in serum T(4) and T(3) but neither time of puberty
      nor pregnancy rates were affected by lowered thyroid hormones.

PMID- 12527087
TI  - Use of primers derived from a new sequence of the bovine Y chromosome for sexing
      Bos taurus and Bos indicus embryos.
AB  - A bovine male-specific marker was identified in our laboratory through random
      amplified polymorphic DNA (RAPD) analysis. This fragment of 3216 bp was cloned,
      sequenced and mapped by fluorescent in situ hybridization (FISH) on the taurine
      Yq. Primers derived from this sequence were initially screened by polymerase
      chain reaction (PCR) for their ability to detect Y-specific segments in zebu and
      taurine genomic DNA. Two of these primers amplified a 655 bp Y-specific sequence
      present in taurine and zebu male genomic DNA. These primers were then used for
      detecting the 655 bp male sequence in DNA from 173 zebu and 30 taurine embryos,
      which had been previously sexed using primers for the sequence BC 1.2. The
      results revealed an accuracy of 100%.

PMID- 12527088
TI  - Apoptosis within bovine follicular cells and its effect on oocyte development
      during in vitro maturation.
AB  - Developmental competence of oocytes is compromised if they originate from atretic
      follicles. Apoptosis is the underlying process of atresia. Apoptotic changes in
      follicular cells are thought to influence the outcome of IVF. The aim of this
      study was to investigate apoptosis in different compartments of single bovine
      follicles (follicular wall, granulosa and cumulus cells (CC)) in relation to COC
      morphology, and to determine whether the addition, in vitro, of exogenous
      follicular cells from atretic follicles to maturing cumulus oocyte complexes
      (COCs) influenced the development of oocytes. Antral follicles were dissected
      from bovine ovaries and opened to obtain COCs and free floating granulosa cells
      (GC). The COCs were classified according to morphology. Apoptosis was determined
      in cumulus and granulosa cells and in homogenates of the remaining follicular
      wall. For every morphological class of COCs, a large variability of apoptotic
      expression was found in all follicle compartments. Follicular wall apoptosis was
      not correlated to COC morphology or to the percentage of apoptotic granulosa or
      cumulus cells. In grade 1 (best morphology) COCs, the degree of apoptosis in
      granulosa cells was comparable to cumulus cell apoptosis (P<0.01). The overall
      expression of apoptosis in granulosa cells of follicles containing grade 3 COCs
      (median+/-median absolute deviation: 37.8+/-13.8%) was significantly higher
      (P<0.05) than in follicles with grade 1 (22.7+/-10.4%) or grade 2 COCs (20.0+/
      17.0%). About 48.3% of grade 3 COCs possessed strongly apoptotic cumulus cells
      compared to 27.8 and 28.2% of grade 1 or grade 2 COCs, respectively. Nonapoptotic
      cumulus complexes were observed in grades 1 and 2 COCs only. Adding exogenous
      follicular cells from atretic follicles to bovine COCs (grades 1 and 2) during in
      vitro maturation (IVM) had no impact on fertilization, blastocyst formation or
      hatching after IVF. This is of particular practical relevance to embryo
      production after ovum pick up (OPU), as during this process, good quality COCs
      are cultured together with simultaneously collected slightly atretic COCs.

PMID- 12527089
TI  - Efficacy of linear and convex transducers for ultrasound-guided transvaginal
      follicle aspiration.
AB  - A new device was developed to hold linear transducers for transvaginal follicle
      aspiration. Efficacy of follicle aspiration was compared using a linear 6 MHz and
      a convex 5 MHz transducer. Fifty-five cows were submitted to follicle aspiration
      at random days of the estrous cycle. Aspirations were conducted with linear
      (n=28) and convex (n=38) transducers with 18 G needles at a negative pressure
      corresponding to 13 ml H(2)O/min. A greater number of follicles were aspirated
      using convex than to linear probe (12.4 versus 7.8, respectively, P<0.05). Mean
      number of oocytes and recovery rates were similar for convex (5.4 and 48.6%) and
      linear (4.6 and 59.3%) transducers. Limited space between the linear transducer
      and needle guide restricted access to some portions of the ovary, reducing the
      number of follicles aspirated using a linear transducer. The newly developed
      adaptor allowed greater stability, holding the ovaries firmly against the linear
      transducer. This diminished mobility permitted a similar number of oocytes to be
      recovered with both transducers. In conclusion, this new adaptor provided a low
      cost alternative for routine follicle aspiration and oocyte recovery in cattle.

PMID- 12527090
TI  - Selective control of the estrous cycle of the dog through suppression of estrus
      and reduction of the length of anestrus.
AB  - The objective of this study was to determine the effectiveness of testosterone in
      suppressing estrus in the bitch, and of cabergoline in shortening the length of
      the subsequent anestrous period. In Experiment 1, 12 diestrual Beagle bitches
      were randomly divided into two groups when plasma progesterone (P(4))
      concentration was <1 ng/ml (Day 0). Starting on Day 0, bitches in Group 1 (n=6)
      were treated with testosterone cypionate every 14 days for a total of 239 days,
      and bitches in Group 2 served as untreated controls. On Day 274, bitches in both
      groups were treated with cabergoline for 40 days and blood samples were obtained
      on Days 274, 276 and 279 for determination of plasma prolactin (PRL)
      concentrations using RIA. All bitches were observed for proestrual bleeding
      during treatment with cabergoline. In Experiment 2, 12 Greyhound bitches
      previously treated with testosterone within the last 6 months were randomly
      divided into two groups. At the initiation of this experiment, P(4) concentration
      was determined to verify that all bitches had a concentration of <1 ng/ml (Day
      0). Starting on Day 0, bitches in Group 1 (n=6) were treated with cabergoline for
      36 days, and bitches in Group 2 (n=6) served as untreated controls. Blood samples
      were obtained on Days 0, 2 and 5 to determine PRL concentrations. All bitches
      were observed for proestrual bleeding during treatment with cabergoline. In
      Experiment 1, one bitch (Group 1) exhibited estrus after treatment with
      testosterone (1mg/kg body weight) for 43 days, and one bitch (Group 1) exhibited
      estrus after treatment with testosterone (2mg/kg body weight) for 113 days. None
      of the other four bitches in Group 1 exhibited estrus during the period of
      testosterone treatment (239 days). All bitches in Group 2 (control) exhibited
      estrus during the 239 days of the study. In addition, five of the six
      testosterone-treated bitches showed signs of proestrual bleeding within an
      average of 12.6 days (range of 5-25 days) after treatment with cabergoline; and,
      four of the six nontestosterone bitches showed signs of proestrual bleeding
      within an average of 28 days (range of 6-46 days). Prolactin concentrations in
      bitches in both Groups 1 and 2 significantly decreased after treatment with
      cabergoline. In Experiment 2, one of the six bitches showed signs of proestrual
      bleeding within 15 days after treatment with cabergoline. From the results of
      this study, it was concluded that exogenous testosterone was moderately effective
      (66%) in suppressing estrus in Beagle bitches, and cabergoline was effective in
      shortening the length of the anestrous period of Beagle bitches whose estrous
      cycle was previously suppressed with exogenous testosterone, but less effective
      in shortening the length of the anestrous period in Greyhound bitches previously
      treated with testosterone to suppress estrus.

PMID- 12527091
TI  - Effects of epidermal growth factor on early embryonic development after in vitro
      fertilization of oocytes collected from ewes treated with follicle stimulating
      hormone.
AB  - Epidermal growth factor (EGF) has been shown to enhance the in vitro rate of
      blastocyst formation in several species. Follicular development was induced in
      ewes (n=15) by twice daily administration of FSH-P on Days 13 and 14 of the
      estrous cycle. Cumulus oocyte complexes (COCs) were collected from all visible
      follicles (n=25+/-2.4/ewe) on Day 15. COCs from each ewe were cultured separately
      for 24h in maturation medium (containing 10% serum, LH, FSH and estradiol) with
      (8.2+/-0.9 per ewe) or without (7.8+/-0.8 per ewe) EGF (10 ng/ml). Oocytes were
      then denuded by hyaluronidase treatment, and healthy oocytes were cultured in the
      presence of frozen-thawed semen in synthetic oviductal fluid (SOF) medium
      containing 2% sheep serum. After 18-20 h, zygotes were transferred to SOF medium
      without glucose and cultured for about 36 h until they reached the 4-8 cell
      stage. Embryos were transferred to SOF medium with glucose for further
      development. Medium was changed every other day until blastocyst formation on Day
      8 of culture (Day 1=day of fertilization). The rate of embryonic development was
      evaluated throughout the culture period. After maturation, cumulus cells were
      more expanded in the presence than in the absence of EGF. The rates of
      fertilization (overall 75.7+/-3.9%) and morula formation (overall 40.6+/-7.1%)
      were similar (P>0.05) for COCs cultured with or without EGF. However, EGF
      increased (P<0.01) the number of blastocysts (1.4+/-0.1 versus 0.6+/-0.2 per ewe)
      and tended to increase (P<0.1) the rate of blastocyst formation (21.0+/-6.6%
      versus 13.4+/-4.3% per ewe). These data demonstrate that EGF increases blastocyst
      formation in FSH-treated ewes. Therefore, EGF is recommended as a supplement to
      maturation medium to enhance embryonic development in vitro in FSH-treated sheep.

PMID- 12527092
TI  - Ovarian response, embryo production and hormonal profile in superovulated goats
      treated with insulin.
AB  - The influence of insulin on ovarian response and embryo production was
      investigated in 30 mixed breed goats, divided randomly into three equal (n=10)
      groups. Goats in Group 1 (control) were superovulated using 20 IU FSH i.m. in six
      divided descending doses, i.e. 4/4, 3/3 and 3/3 IU at 12 h interval for three
      consecutive days and were not given insulin treatment. Goats in Group 2 (insulin
      pretreatment) were pretreated with long acting purified bovine insulin 0.2 IU/kg
      body weight per day s.c. on Days 7, 8 and 9 of the estrous cycle prior to
      initiation of superovulatory treatment as in Group 1. Animals in Group 3 (insulin
      cotreatment) were treated as in Group I, but in addition received long acting
      purified bovine insulin 0.2 IU/kg body weight per day s.c. as a cotreatment along
      with the first, third and fifth FSH treatments on three consecutive days. Total
      ovarian response (corpus luteum and unovulated large follicle (UOLF)) was
      significantly (P<0.05) higher in insulin pretreatment (17.90+/-3.08) than in the
      cotreatment (11.50+/-2.34) and control (11.90+/-1.87) groups. The number of UOLF
      was significantly higher (P<0.05) in the insulin pretreatment (10.2+/-1.67) than
      the cotreatment (4.9+/-1.14) and control (3.6+/-1.09) groups. The mean
      transferable quality of embryos did not differ significantly among treatments.
      Progesterone concentration on the day of PGF(2)alpha treatment was not different
      (P>0.05) between the insulin treatment groups (5.28+/-0.79; 5.30+/-0.66 ng/ml).
      Estradiol-17beta concentration was significantly (P<0.05) higher on the day of
      PGF(2)alpha treatment in both the insulin treatment groups (36.67+/-6.40; 34.33+/
      4.33 pg/ml) as compared to the control group (20.00+/-2.73 pg/ml). There is ample
      evidence to indicate beneficial effect of insulin on folliculogenesis and
      steroidogenesis in superovulated goats.

PMID- 12527093
TI  - Rabbit and pig ear skin sample cryobanking: effects of storage time and
      temperature of the whole ear extirpated immediately after death.
AB  - The post-mortem temporal and thermal limits within which there will be ample
      guarantees of rescuing living skin cells from dead specimens of two species,
      rabbit and pig, were studied. Post-mortem extirpated whole ears were stored (in
      non-aseptic conditions) either at 4 degrees C or at room temperature (from 22 to
      25 degrees C) or at 35 degrees C for different time lapses after animal death. In
      both species, the post-mortem maximum time lapses where cell viability was not
      significantly reduced were 240, 72, and 24 h post-mortem (hpm) for 4, 22-25 and
      35 degrees C, respectively. Once the post-mortem temporal limits for each tested
      thermal level at which cells from skin samples are able to grow in culture were
      defined, the survival ability of skin samples submitted to these temporal limits
      and cryopreserved were tested. In the pig, skin samples stored at the three
      tested thermal levels survived after vitrification-warming, reaching confluence
      in culture. In rabbit, only tissue samples from ears stored at 35 degrees C for
      24 hpm did not survive after vitrification-warming. In conclusion, we should
      remark that cell survival rates obtained according to the assayed post-mortem
      time lapses and thermal levels are sufficient to collect and to cryopreserve skin
      samples from the majority of dead specimens.

PMID- 12527094
TI  - Exogenous prostaglandin F(2)alpha at time of ovulation improves reproductive
      efficiency in repeat breeder sows.
AB  - In order to determine if PGF(2)alpha could improve fertility in repeat breeder
      females when added to semen used for artificial insemination (AI) the following
      trial was performed. In a large indoor Hungarian production unit of 2000 sows,
      667 repeat breeding females were assigned to two groups and were treated as
      follows: Group 1 (n=322), received PGF(2)alpha, added to the semen immediately
      before AI; Group 2 (n=345), received AI with untreated semen. Conception rate,
      farrowing rate, subsequent total and live born litter size and subsequent weaning
      to estrus intervals were evaluated. Conception and farrowing rates revealed
      highly significant differences between the PGF(2)alpha-treated and nontreated
      animals (P<0.001). Subsequent total born (P<0.07), and live born litter size
      (P<0.13), and subsequent weaning to estrus intervals (P<0.23) showed no
      significant differences. It is reasonable to suggest that exogenous PGF(2)alpha
      added to AI semen improves conception and farrowing rates.

PMID- 12527095
TI  - Cortical representation of vowels reflects acoustic dissimilarity determined by
      formant frequencies.
AB  - We studied neuromagnetic correlates of the processing of German vowels [a], [e]
      and [i]. The aim was (i) to show an influence of acoustic/phonetic features on
      timing and mapping of the N100 m component and (ii) to demonstrate the retest
      reliability of these parameters. To assess the spatial configuration of the N100
      m generators, Euclidean distances between vowel sources were computed. Latency,
      amplitude, and source locations of the N100 m component differed between vowels.
      The acoustically most dissimilar vowels [a] and [i] showed more distant source
      locations than the more similar vowels [e] and [i]. This pattern of results was
      reliably found in a second experimental session after at least 5 days. The
      results suggest the preservation of spectral dissimilarities as mapped in a F(1)
      F(2) vowel space in a cortical representation.

PMID- 12527096
TI  - An ERP study of continuous speech processing. II. Segmentation, semantics, and
      syntax in non-native speakers.
AB  - Behavioral and electrophysiological studies indicate that altered language
      experience has different effects on distinct subsystems within language. In this
      study, we recorded event-related potentials (ERPs) in native Japanese late
      learners of English listening to English sentences. ERP indices of semantic
      processing, syntactic processing, and speech segmentation were compared and
      contrasted for native Japanese and previously tested native English speakers.
      Native and non-native speakers showed similar semantic processing effects
      including an N400 for words as opposed to nonwords. In contrast, native Japanese
      speakers showed none of the effects associated with syntactic processing in
      native English speakers including an anterior negativity to nonwords presented in
      a syntactic context. Furthermore, the ERP word-onset effect evident in native
      English speakers was not found for the native Japanese speakers in this study.
      These data contribute additional and specific evidence to the proposal that
      subsystems within language display varying degrees of plasticity.

PMID- 12527097
TI  - An ERP study of continuous speech processing. I. Segmentation, semantics, and
      syntax in native speakers.
AB  - Speech segmentation, breaking continuous streams of sound into units that can be
      recognized, is a necessary step in auditory language processing. To date, most
      studies of speech segmentation have been limited to behavioral measures that may
      not index online segmentation as it occurs when listening to natural speech. In
      the present study, we measured event-related potentials (ERPs) evoked by word
      initial and word-medial syllables equated for loudness, length, and phonemic
      content. This comparison provided an online measure of natural speech
      segmentation. Word-initial sounds elicited a larger early sensory component
      (N100). In addition, we measured the effects of semantic and syntactic
      information on speech segmentation by comparing ERPs to word-initial and word
      medial syllables in sentences with varying amounts of semantic and syntactic
      content. The results indicated that neither semantic nor syntactic information is
      necessary for the word-onset segmentation effect to be observed. We also
      identified additional ERP components that index more general semantic and
      syntactic aspects of natural speech processing.

PMID- 12527098
TI  - Modulation of a brain-behavior relationship in verbal working memory by rTMS.
AB  - We investigated whether the brain-behavior relationship (BBR) between regional
      cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and
      individual accuracy in verbal working memory (WM) can be modulated by repetitive
      transcranial magnetic stimulation (rTMS) of the left or right middle frontal
      gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4
      Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using
      letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole
      brain functional images were acquired. A hypothesis-driven region-of-interest
      analysis of the left and right MFG BBR as well as an explorative whole-brain
      analysis correlating the individual accuracy with rCBF was carried out. Without
      rTMS we found a negative BBR in the left but no significant BBR in the right MFG.
      This negative BBR is best explained by an increased effort of volunteers with an
      inferior task performance. Left-sided rTMS led to a shift of the BBR towards the
      superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left
      SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left
      inferior frontal gyrus. Beyond the cognitive subtraction approach this
      correlation analysis provides information on how the prefrontal cortex is
      involved based on individual performance in working memory. The results are
      discussed along the idea of a short-term plasticity in an active neuronal network
      that reacts to an rTMS-induced temporary disruption of two different network
      modules.

PMID- 12527100
TI  - Information flow in the mental lexicon during speech planning: evidence from
      event-related brain potentials.
AB  - A major issue in speech production research is the question of how speakers
      retrieve words from the so-called mental lexicon. Current models of lexical
      retrieval converge on the assumption that category associates of a target word
      are semantically activated during speech planning. However, the question of
      whether these competitors are also phonologically activated is less agreed on.
      Past research has addressed this issue by testing whether lexical retrieval of a
      picture name (e.g. sheep) affects, or is affected by, the processing of a word
      that is phonologically related to a semantic category associate to the picture
      name (e.g. goal, phonologically related to goat). Behavioral studies have failed
      to obtain such so-called mediated priming effects, but have been questioned on
      the grounds of possibly insufficient task sensitivity. As such priming effects
      have reliably been obtained with event-related brain potentials in word
      recognition, we used this approach for testing these effects in lexical retrieval
      during speech planning. Our results consistently demonstrate the absence of
      mediated priming effects, putting strong constraints on the activation flow in
      the mental lexicon during speech planning.

PMID- 12527099
TI  - Cortical and cerebellar activity of the human brain during imagined and executed
      unimanual and bimanual action sequences: a functional MRI study.
AB  - The neural (blood oxygenation level dependent) correlates of executed and
      imagined finger sequences, both unimanual and bimanual, were studied in adult
      right-handed volunteers using functional magnetic resonance imaging (fMRI) of the
      entire brain. The finger to thumb opposition tasks each consisted of three
      conditions, two unimanual and one bimanual. Each experimental condition consisted
      of overt movement of the fingers in a prescribed sequence and imagery of the same
      task. An intricate network consisting of sensorimotor cortex, supplementary motor
      area (SMA), superior parietal lobule and cerebellum was identified when the tasks
      involved both planning and execution. During imagery alone, however, cerebellar
      activity was largely absent. This apparent decoupling of sensorimotor cortical
      and cerebellar areas during imagined movement sequences, suggests that cortico
      cerebellar loops are engaged only when action sequences are both intended and
      realized. In line with recent models of motor control, the cerebellum may monitor
      cortical output and feed back corrective information to the motor cortex
      primarily during actual, not imagined, movements. Although parietal cortex
      activation occurred during both execution and imagery tasks, it was most
      consistently present during bimanual action sequences. The engagement of the
      superior parietal lobule appears to be related to the increased attention and
      memory resources associated, in the present instance, with coordinating difficult
      bimanual sequences.

PMID- 12527101
TI  - Visual dream content, graphical representation and EEG alpha activity in
      congenitally blind subjects.
AB  - It is currently claimed that congenitally blind do not have visual imagery and
      are therefore unable to present visual contents in their dreams. The aim of our
      study was to quantitatively evaluate the existence of visual imagery in born
      blind dreams and to correlate it with objective measures, such as sleep EEG
      frequency components, namely with alpha attenuation (regarded as an indicator of
      visual activity), and graphical analysis of dream pictorial representations. The
      investigation was carried out via simultaneous recordings of dream reports and
      polysomnography, during nocturnal sleep at volunteers' homes; scheduled regular
      awakenings during the night provided the data for dream and EEG analysis. In the
      morning, subjects were asked to make a drawing of their dream images.
      Congenitally blind (n=10) were comparable to normal sighted subjects (n=9): the
      two groups presented equivalent visual activity indices, and no differences in
      the analysis of graphical representation of dreaming imagery. However, blind
      subjects presented a lower rate of dream recall than sighted (27% versus 42%).
      Both groups had significant negative correlation between Visual Activity Index
      (VAI) and alpha power in the central and occipital O2 derivations (blind: C4: r=
      0.615, P<0.005; O2: r=-0.608, P<0.006; sighted: C4: r=-0.633, P<0.01; O2: r=
      0.506, P<0.05). This correlation was weaker for the blind in O1 (r=-0.573,
      P<0.05) and non-existent for the sighted. Blind individuals have significantly
      lower alpha activity in the central derivation. In conclusion, the congenitally
      blind have visual content in their dreams and are able to draw it and, as
      expected, their VAI is negatively correlated with EEG alpha power.

PMID- 12527102
TI  - Information flow related to visual search assessed using magnetoencephalography.
AB  - The sequence of neural activation during a visual search task was investigated
      using magnetoencephalography and the source locations for the activations were
      analyzed using a single-dipole algorithm. Five components (M1-5) were detected at
      mean latencies of 110, 146, 196, 250 and 333 ms in both of two different stimulus
      conditions; a target popped out in one stimulus condition (pop-out), while it did
      not in the other condition (non-pop-out). Statistical analysis showed that the M3
      amplitude was larger and the M5 latency was shorter in the pop-out condition than
      in the non-pop-out condition, while there was no difference in the other
      components between the conditions. Neural sources were localized in the calcarine
      sulcus (M1) and the posterior fusiform gyrus (M2) of the hemisphere contralateral
      to the stimuli, the intraparietal sulcus and the posterior superior temporal
      sulcus (M3) in either of the hemispheres, and the calcarine sulcus (M4) of the
      same hemisphere in which the early processing (M1 and M2) occurred. The criteria
      for source localization were not satisfied for M5. The results suggest that the
      processing for pop-out and non-pop-out stimuli share a common mechanism; after
      early feature processing in the occipital cortex (M1 and M2), visual information
      is processed in the parietal and temporal regions (M3) and then some of this
      information is fed back to the occipital cortex (M4).

PMID- 12527103
TI  - Premotor cortex in observing erroneous action: an fMRI study.
AB  - The lateral premotor cortex (PMC) is involved during action observation in
      monkeys and humans, reflecting a matching process between observed actions and
      their corresponding motor schemata. In the present study, functional magnetic
      resonance imaging (fMRI) was used to investigate if paying attention to the two
      observable action components, objects and movements, modulates premotor
      activation during the observation of actions. Participants were asked to classify
      presented movies as showing correct actions, erroneous actions, or senseless
      movements. Erroneous actions were incorrect either with regard to employed
      objects, or to performed movements. The experiment yielded two major results: (1)
      The ventrolateral premotor cortex (vPMC) and the anterior part of the
      intraparietal sulcus (aIPS) are strongly activated during the observation of
      actions in humans. Premotor activation was dominantly located within Brodmann
      Area (BA) 6, and sometimes extended into BA 44. (2) The presentation of object
      errors and movements errors allowed to disentangle brain activations
      corresponding to the analysis of movements and objects in observed actions. Left
      premotor areas were more involved in the analysis of objects, whereas right
      premotor areas were dominant in the analysis of movements. It is suggested that
      the analysis of categorical information, like objects, and that of coordinate
      information, like movements, are pronounced in different hemispheres.

PMID- 12527104
TI  - Shifts of attention in light and in darkness: an ERP study of supramodal
      attentional control and crossmodal links in spatial attention.
AB  - Crossmodal links in spatial attention, uncovered by recent behavioural and
      electrophysiological studies, have been interpreted as evidence for supramodal
      processes controlling shifts of attention. However, previous experiments have
      usually been conducted in illuminated environments. Continuously available visuo
      spatial information might result in shifts of attention being primarily guided by
      visible information, even when another modality is task-relevant. The present ERP
      study evaluated this. A symbolic auditory cue directed attention to the left or
      right hand. Participants had to detect infrequent tactile targets delivered to
      the cued hand, while ignoring any visual stimuli. Stimuli were presented either
      in a lit environment or in darkness. Although continuous ambient visuo-spatial
      information was eliminated in the latter condition, processing of task-irrelevant
      visual events was still modulated by spatial attention for the tactile task.
      Moreover, ERP correlates of attentional shifts in the cue-target interval were
      similar for both illumination conditions. This was further confirmed in a follow
      up experiment where the darkness condition was repeated without any peripheral
      visual stimulation ever occurring. These findings demonstrate that the ERP
      correlates of crossmodal attention (both preparatory effects in the cue-target
      interval, and also modulations of stimulus-evoked components) do not depend on
      selection being guided by ambient visible information in a lit environment. They
      suggest instead that spatial shifts of attention are controlled supramodally.

PMID- 12527105
TI  - Integration process of contours defined by different attributes.
AB  - We examined how contours defined by different attributes are integrated into a
      shape using the visual search paradigm and found that the search for the bar
      orientation is particularly difficult when each bar is composed of motion-defined
      and luminance- or color-defined contours. This does not support the view that the
      shape integration process is based on the unified contour representation entirely
      common to all attributes, but suggests that motion-defined contours are
      integrated through a different process.

PMID- 12527106
TI  - Genetic regulation of cell function in response to iron overload or chelation.
AB  - Iron influences many aspects of cell function on different biochemical levels.
      This review considers effects mediated through iron-dependent changes in gene
      expression in mammalian cells. Several classes of related genes are responsive to
      cellular iron levels, but no clear patterns readily account for the toxicity of
      iron overload or the consequences of removal of iron with chelating agents. Here
      we group some of the genes influenced by iron status into those related to iron
      metabolism, oxygen and oxidative stress, energy metabolism, cell cycle
      regulation, and tissue fibrosis. Iron excess and chelation do not generally
      result in a continuous or graded transcriptional response, but indicate operation
      of distinct mechanisms. An emerging concept is that iron signals through
      generation of reactive oxygen species to activate transcription factors such as
      NF-kappaB, whereas iron removal mimics hypoxia, perhaps by disrupting iron-based
      O(2) sensors and influencing gene expression through, e.g., the hypoxia-inducible
      factor, HIF-1. Heme and other metalloporphyrins have other distinct mechanisms
      for regulating transcription. Regulation of gene expression through iron
      responsive elements in mRNAs coded by several genes is one of the best understood
      mechanisms of translational control.

PMID- 12527107
TI  - Galectin 1 inhibits incorporation of vitronectin and chondroitin sulfate B into
      the extracellular matrix of human vascular smooth muscle cells.
AB  - Galectin-1, a beta-galactoside-binding dimeric lectin, interacts with the
      extracellular matrix (ECM) of smooth muscle cells (SMCs) and with particular ECM
      proteins. Enrichment of the ECM with galectin-1 affects adhesion and
      proliferation of cultured SMCs. Here we investigated whether galectin-1 (1)
      interacts with glycosaminoglycan (GAG) chains, (2) cross-links between ligands
      and facilitates the incorporation of GAGs, vitronectin and plasma fibronectin in
      the ECM of vascular SMCs. A recombinant galectin-1 fusion protein GalH, used in
      this study, formed dimers and interacted with ECM proteins. GAG chains inhibited
      these interactions. Among the studied GAG chains, only chondroitin sulfate B
      interacted with GalH in beta-galactoside-dependent manner. GalH did not bridge
      between ECM proteins on solid phase and [125I]-labelled ECM proteins or GAGs in
      solution. The ECM incorporated less vitronectin in the presence of soluble GalH.
      GalH-enriched ECM incorporated less vitronectin and chondroitin sulfate B. The
      ECM partially depleted of endogenous galectins incorporated more chondroitin
      sulfate B compared to untreated ECM. These results suggest that galectin-1 is
      likely to be involved in the ECM assembly affecting incorporation of some ECM
      components important for SMC behaviour.

PMID- 12527108
TI  - N-glycosylation of recombinant human fucosyltransferase III is required for its
      in vivo folding in mammalian and insect cells.
AB  - Human alpha3/4fucosyltransferase (FT3) catalyses the synthesis of fucosylated
      glycoconjugates involved in cell-cell interactions. FT3 has two potential N
      glycosylation sites at Asn(154) and Asn(185). Soluble secretory forms of the
      enzyme (SFT3) and mutant forms with the first, second and both glycosylation
      sites (SFT3DN1, SFT3DN2, SFT3DN) mutated have been expressed in baby hamster
      kidney (BHK) and Spodoptera frugiperda (Sf9) cells. Deletion of the first or both
      sites caused total enzyme inactivation. Deletion of the second site caused 99%
      and 75% decrease of secretory enzyme expression in BHK and Sf9 cells,
      respectively. Sf9 cells produced 1 mg/l SFT3 and 0.3 mg/l SFT3DN2; these values
      were 175- and 3750-fold higher, respectively, than those observed for BHK cells.
      A significant amount of protein was accumulated intracellularly in Sf9 cells
      which for SFT3 was active and for SFT3DN2 was inactive, indicating the importance
      of the glycans from the second glycosylation site for protein folding. The
      corresponding full-length forms FT3, FT3DN1 and FT3DN2 associated with calnexin
      as observed by immunoprecipitation studies, which indicated the possible role of
      this chaperon in the folding of glycosylated glycosyltransferases.

PMID- 12527109
TI  - A His-tag based immobilization method for the preparation and reconstitution of
      apoflavoproteins.
AB  - The NifL PAS domain from Azotobacter vinelandii is a flavoprotein with FAD as the
      prosthetic group. Here we describe a novel immobilization procedure for the large
      scale preparation of apo NifL PAS domain and its efficient reconstitution with
      either 2,4a-13C-FAD or 2,4a-13C-FMN. In this procedure, the His-tagged
      holoprotein is bound to an immobilized metal affinity column and the flavin is
      released by washing the column with buffer containing 2 M KBr and 2 M urea. The
      apoprotein is reconstituted on-column with the (artificial) flavin cofactor, and
      then eluted with buffer containing 250 mM imidazole. Alternatively, the
      immobilized apoprotein can be released from the column matrix before
      reconstitution. The His-tag based immobilization method of preparing
      reconstituted (or apo) NifL PAS domain protein has the advantage that it combines
      a protein affinity chromatography technique with limited protein loss, resulting
      in a high protein yield with extremely efficient flavin reconstitution. This on
      column reconstitution method can also be used in cases where the apoprotein is
      unstable. Therefore, it may develop as a universal method for replacement of
      flavin or other cofactors.

PMID- 12527110
TI  - Cytoagglutination and cytotoxicity of Wheat Germ Agglutinin isolectins against
      normal lymphocytes and cultured leukemic cell lines--relationship between
      structure and biological activity.
AB  - The relationships between degree of lectin-cell binding, cytotoxicity and
      cytoagglutinating activity of three Wheat Germ Agglutinin isolectins (WGA-1, WGA
      2, WGA-3) against normal lymphocytes and cultured leukemic cell lines (Jurkat,
      MOLT-4, Raji, Daudi, K-562) were studied. All WGA-isolectins interacted in a
      similar degree with normal lymphocytes, while in the case of leukemic cells, the
      degree of isolectin-cell binding increased in the order: WGA-1< or =WGA-3<WGA-2
      at isolectin concentrations 0.5 microM and higher, and WGA-3<WGA-2< or =WGA-1 at
      0.25 microM isolectin concentration. The WGA interacted in higher degree with
      Jurkat, Raji, Daudi and K-562, followed by MOLT-4 and normal lymphocytes. The
      velocity of cytoagglutination in the presence of 0.25 microM WGA-isolectins
      increased in the order: WGA-3<WGA-2< or =WGA-1, and was better expressed in
      Jurkat, Raji, Daudi and K-562, followed by MOLT-4 and normal lymphocytes. The
      cytotoxicity of isolectins was very well expressed against Jurkat, MOLT-4, Raji
      and Daudi, and less expressed against K-562 and normal lymphocytes. In the case
      of leukemic cells, the cytotoxic effect of WGA-isolectins increased in the order:
      WGA-3<WGA-2=WGA-1. A very good positive correlation was determined between
      velocity of cytoagglutination and degree of lectin-cell binding (r=0.77,
      P<0.001). A good inverse correlation was found between cytotoxicity and degree of
      lectin-cell binding (r=-0.34, P<0.001), and poor correlation was observed between
      cytotoxicity and cytoagglutinating activity of WGA-isolectins (r=0.16, P<0.01).
      The results suggest that the WGA-isolectins, structurally distinguishable in only
      several amino acid sequences, interacted in different degrees with leukemic cells
      and manifested different cytoagglutinating and cytotoxic activity.

PMID- 12527111
TI  - Cellular environment of metabolites and a metabonomic study of tamoxifen in
      endometrial cells using gradient high resolution magic angle spinning 1H NMR
      spectroscopy.
AB  - High resolution magic angle spinning (HRMAS) 1H NMR spectroscopy was used to
      metabolically characterise Ishikawa cells, a human cell line derived from
      endometrial adenocarcinoma. The spectra obtained had well-resolved resonances
      from the nucleotide derivatives of uridine and adenosine. Using a combination of
      diffusion- and relaxation-weighted spectroscopy, the cellular environment of key
      metabolites previously identified as related to cell growth was also
      investigated. As Ishikawa cells are hormone-responsive, the metabolic action of
      tamoxifen, a selective estrogen receptor modulator (SERM), was also investigated.
      Cells were exposed to 5, 1 and 0.1 microM tamoxifen. Using the statistical
      regression technique of prediction to latent structures by partial least squares,
      a predictive model was built modelling the metabolic profile of the cells against
      exposure to tamoxifen. These spectral changes were characterised by increased
      resonance intensities from ethanolamine (3.26 ppm), glucose (3.34-3.94 ppm),
      glutamate (2.14, 2.32 ppm), tyrosine (7.24 ppm), uridine (7.85 ppm) and adenosine
      (8.20 ppm), and a relative decrease in contributions from myo-inositol resonances
      (3.30, 3.62, 3.55 ppm). The nucleotide changes suggest that tamoxifen affects RNA
      transcription, while the changes in ethanolamine and myo-inositol concentrations
      are indicative of cell membrane turnover.

PMID- 12527112
TI  - Agmatine modulates the in vivo biosynthesis and interconversion of polyamines and
      cell proliferation.
AB  - Agmatine has recently gained wide interest as a bioactive arginine metabolite
      with a multitude of physiological functions. This study evaluates the in vivo
      role of agmatine in the modulation of metabolism and intracellular level of
      polyamines. Here, we report that agmatine, administered to mice, differentially
      affects the renal and liver activity of the two key enzymes regulating polyamine
      biosynthesis and interconversion/degradation. Thus, agmatine exerts a negative
      regulation of ODC activity and protein content, and positive regulation of SSAT
      activity, having no effect on ODC and SSAT transcript level. Agmatine modulation
      of ODC and SSAT activities is noticeably augmented by the inhibitor of its
      catabolism, aminoguanidine. Antizyme and eIF4E protein content appears to be
      affected by agmatine only insignificantly and apparently do not contribute to
      agmatine-induced down-regulation of ODC content. The homeostasis of spermidine
      and spermine is preserved after agmatine injection, while the putrescine level
      decreases. Furthermore, when tested in a mouse kidney injury model, agmatine,
      partially but significantly, reduces [3H] thymidine incorporation into DNA. This
      is consistent with suppressed renal tubule epithelial cell proliferation. The
      findings provide in vivo evidence of a substantial role of agmatine as a
      modulator of polyamine biosynthesis and degradation and suggest its suppressive
      effect on cell proliferation.

PMID- 12527113
TI  - Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau
      proteins--a role in nuclear localization.
AB  - Both phosphorylation and O-GlcNAc glycosylation posttranslationally modify
      microtubule-associated Tau proteins. Whereas the hyperphosphorylation of these
      proteins that occurs in Alzheimer's disease is well characterized, little is
      known about the O-GlcNAc glycosylation. The present study demonstrates that a
      balance exists between phosphorylation and O-GlcNAc glycosylation of Tau
      proteins, and furthermore that a dysfunction of this balance correlates with
      reduced nuclear localization. The affinity of Tau proteins for WGA lectin,
      together with evidence from [3H]-galactose transfer and analysis of beta
      eliminated products, demonstrated the presence of O-GlcNAc residues on both
      cytosolic and nuclear Tau proteins. In addition, our data indicated the existence
      of a balance between phosphorylation and O-GlcNAc glycosylation events. Indeed,
      as demonstrated by 2D-electrophoresis and Western blotting, O-GlcNAc residues
      were mainly located on the less phosphorylated Tau 441 variants, whereas the more
      phosphorylated forms were devoid of O-GlcNAc residues. Furthermore, the Tau
      protein hyperphosphorylation induced by cellular okadaic acid treatment was
      correlated with reduced incorporation of O-GlcNAc residues into Tau proteins and
      with diminished Tau transfer into the nucleus. Hence, this paper establishes a
      direct relationship between O-GlcNAc glycosylation, phosphorylation and cellular
      localization of Tau proteins.

PMID- 12527114
TI  - Hydrolysis of pyridoxal isonicotinoyl hydrazone and its analogs.
AB  - An orally available iron chelator is desirable for the treatment of secondary
      iron overload. Pyridoxal isonicotinoyl hydrazone (PIH) and its analogs
      effectively mobilize iron in vivo and in vitro, and are therefore promising
      candidates for this purpose. PIH analogs undergo significant amino acid-catalyzed
      hydrolysis in cell culture medium and in serum, achieving equilibrium with their
      corresponding aldehydes and hydrazides with half-times of 1-8 h. The extent of
      hydrolysis in RPMI is significant, even in experiments of a few hours' duration,
      although the half-life of PIH in phosphate-buffered saline (PBS) is approximately
      24 h. Therefore, the biological effects (e.g., 59Fe mobilization, toxicity) of
      these iron chelators have been underestimated in previous studies. Measurement of
      the affinity of PIH analogs for Fe(3+) under conditions in which hydrolysis is
      minimal resulted in conditional affinity constants of 10(26) to 10(27) M, which
      are much lower than predicted by the overall formation constants determined under
      conditions that likely allowed extensive hydrolysis. These data indicate the
      importance of hydrolysis of PIH analogs in the interpretation of previous
      studies, and the importance of designing clinically useful analogs whose
      efficacies are not limited by hydrolysis.

PMID- 12527115
TI  - Contribution of spermidine to stimulation by hepatocyte growth factor in repair
      after damage of rabbit gastric mucosal cells in primary culture.
AB  - Wound-healing of the gastric mucosa is suggested to be stimulated by hepatocyte
      growth factor (HGF). Polyamines are shown to contribute to repair after damage in
      the gastric mucosa. The present study was designed to elucidate whether HGF can
      stimulate wound-healing of the gastric mucosa via polyamine production, using
      rabbit gastric mucosal cells in primary culture. A wound was made as a round cell
      free area in the cell sheet of confluent cultured cells. When HGF was added to
      the culture medium, such denuded area was significantly reduced in size compared
      with the control, but the reduction was inhibited by addition of D,L-alpha
      difluoromethylornithine (DFMO), an inhibitor of a rate-limiting enzyme (ornithine
      decarboxylase) of polyamine biosynthesis, to the culture medium. However, the
      inhibitory effect by DFMO was reversed by pretreatment with spermidine, but not
      with putrescine. Intracellular levels of polyamines in the whole confluent cells
      including the cells around the denuded area were not changed by addition of HGF,
      but putrescine and spermidine levels were decreased by further addition of DFMO.
      We conclude that spermidine may be involved in stimulation by HGF in the repair
      after damage of gastric mucosal cells.

PMID- 12527117
TI  - Excitation energy transport and trapping in concentrated solid solutions of
      flavomononucleotide.
AB  - Excitation energy transport and trapping is studied for monomer-fluorescent dimer
      system of flavomononucleotide (FMN) in polyvinyl alcohol films (PVA). It is shown
      that the theory neglecting reverse energy transfer (RET) from dimers to monomers
      does not allow for the explanation of concentration quenching and concentration
      depolarization results presented herein. Much better agreement has been obtained
      using generalized energy transport theory in which fluorescent dimers are treated
      as imperfect traps for excitation energy. Such parameters like the dimer quantum
      yield and its emission anisotropy are estimated.

PMID- 12527116
TI  - In vitro splicing of erythropoietin by the Mycobacterium tuberculosis RecA intein
      without substituting amino acids at the splice junctions.
AB  - Protein splicing is a self-catalyzed process involving the excision of an
      intervening polypeptide sequence, the intein, and joining of the flanking
      polypeptide sequences, the extein, by a peptide bond. We have studied the in
      vitro splicing of erythropoietin (EPO) using a truncated form of the
      Mycobacterium tuberculosis RecA mini-intein in which the homing endonuclease
      domain was replaced with a hexahistidine sequence (His-tag). The intein was
      inserted adjacent to cysteine residues to assure that the spliced product had the
      natural amino acid sequence. When expressed in Escherichia coli, intein
      containing EPO was found entirely as inclusion bodies but could be refolded in
      soluble form in the presence of 0.5 M arginine. Protein splicing of the refolded
      protein could be induced with a reducing agent such as DTT or tris(2
      carboxyethyl)phosphine and led to the formation of EPO and mini-intein along with
      some cleavage products. Protein splicing mediated by the RecA intein requires the
      presence of a cysteine residue adjacent to the intein insertion site. We compared
      the efficiencies of protein splicing adjacent to three of the four cysteine
      residues of EPO (Cys29, Cys33 and Cys161) and found that insertion of intein
      adjacent to Cys29 allowed far more efficient protein splicing than insertion
      adjacent to Cys33 or Cys161. For ease of purification, our experiments involved a
      His-tagged EPO fusion protein and a His-tagged intein and the spliced products
      (25 kDa EPO and 24 kDa mini-intein) were identified by Western blotting using
      anti-EPO and anti-His-tag antibodies and by mass spectroscopy. The optimal
      splicing yield at Cys29 (40%) occurred at pH 7.0 after refolding at 4 degrees C
      and splicing for 18 h at 25 degrees C in the presence of 1 mM DTT.

PMID- 12527118
TI  - Human milk contains S100B protein.
AB  - The present study constitutes the first finding of the calcium-binding protein
      S100B and of its mRNA in human milk, as revealed by a quantitative
      immunoluminometric assay, by Western blot analysis and by reverse transcription
      polymerase chain reaction (RT-PCR) assay followed by restriction enzyme
      digestion. The concentration of S100B in milk is markedly higher than that
      observed in other biological fluids such as cord blood, peripheral blood, urine,
      cerebrospinal fluid and amniotic fluid. This finding could be related to a
      possible trophic role, which has been hypothesized for the protein.

PMID- 12527119
TI  - Binding of hydrophobic ligands by Pseudomonas aeruginosa PA-I lectin.
AB  - The ability of Pseudomonas aeruginosa PA-I lectin to bind the fluorescent
      hydrophobic probe, 2-(p-toluidinyl) naphthalene sulfonic acid (TNS), and adenine
      was examined by spectrofluorametry and equilibrium dialysis. Interaction of TNS
      with PA-I caused significant enhancement of TNS fluorescence. The Hill
      coefficient (3.8+/-0.3) and the dissociation constant (8.7+/-0.16 microM) showed
      that TNS probably bound to four high affinity hydrophobic sites per PA-I
      tetramer. Interactions between PA-I and adenine were examined by equilibrium
      dialysis using [3H] adenine. The results indicated the presence of at least two
      classes of binding sites--one high and four lower affinity sites per tetramer
      with dissociation constants of 3.7+/-1.5 and 42.6+/-1.2 microM, respectively.
      These were distinct from the TNS sites as titration of TNS-equilibrated PA-I with
      adenine caused TNS fluorescence enhancement. The titration curve confirmed the
      existence of two classes of adenine-binding sites. Conversely, when PA-I was
      first equilibrated with adenine and then titrated with TNS, no TNS-binding was
      registered. This may indicate that conformational rearrangements of the lectin
      molecule caused by adenine prevent allosterically TNS binding.

PMID- 12527122
TI  - Afferent response parameters derived from postmasker probe-detection thresholds:
      'the decay of sensation' revisited.
AB  - The classical model of forward masking postulates that the detection threshold
      for a tone probe that follows a stimulus of similar frequency content is elevated
      relative to the quiet threshold because the probe must evoke a just-detectable
      increment in a decaying postmasker sensation. That postmasker decay is charted by
      probe-detection thresholds if the sensation increment is small and constant. This
      model was examined for a 2-kHz Gaussian-shaped probe and a 2-kHz forward masker,
      based on the model's assumption that a just-detectable increment in sensation
      results from a just-detectable increment in level. Psychometric functions for
      detection were obtained at 2.5-30 ms postmasker. Their means and standard
      deviations generally decreased with delay. It was assumed that standard deviation
      is related to the putative just-detectable level increment by a simple monotonic
      transformation. Thus, if the standard deviation of the psychometric function for
      probe detection is neither small nor constant, then the corresponding just
      detectable increment in level is neither small nor constant, and the just
      detectable increment in sensation is neither small nor constant. The classical
      model also fails to allow for the variability of internal events. The concept of
      detection threshold as a sensation increment was preserved in a Signal Detection
      model, that does allow for internal variability. In this model the postmasker
      residual is the input to a probe detector. The new model produces an equation for
      the just-detectable level increment as a function of probe delay. Comparison data
      were generated by again assuming some relation between the standard deviation of
      the psychometric function for detection, and the just-detectable increment in
      level. The fit of equation to data yields robust values for the probe detector's
      maximum firing rate, dynamic range, and spike-counting time. All that is required
      to account for the decay of sensation, for a pure tone, is a single neuron
      operating at some higher center.

PMID- 12527121
TI  - Identification of gene expression profiles in rat ears with cDNA microarrays.
AB  - The physiological processes of hearing implicate thousands of molecules acting in
      harmony; however, their identities are only partially understood. We used cDNA
      microarrays containing 1,176 genes to identify >150 genes expressed in rat middle
      and inner ear tissue. Expressed genes covered several gene families and
      biological pathways, many of which have previously not been described.
      Transcription factor genes that were expressed included inhibitors of DNA binding
      protein (Id). These were localized to the spiral ganglion, organ of Corti and
      stria vascularis, and they are possibly involved in neurogenesis and
      angiogenesis. Transcriptional factors that were highly expressed included Gax
      (homeobox) and I-kappaB, which inhibit cellular proliferation. Their presence
      suggests that inhibitory programs for cell proliferation are enforced in the ear.
      Ion channel genes that were expressed included voltage-dependent L-type calcium
      channels (LTCC) and proton-gated cation channels (PGCC). Genes involved in
      neurotransmitter production and release included glutamic acid decarboxylase
      (GAD1). Genes involved in postsynaptic inhibition included neuropeptide Y5
      receptors (NPY5) and GAD1. Due to the existence of receptors and/or enzymes
      involved in their biochemical synthesis, neurotransmitters associated with these
      might include serotonin, glutamide, acetylcholine, gamma-aminobutyric acid
      (GABA), neurotensin, and dopamine.

PMID- 12527123
TI  - Frog saccular hair cells dissociated with protease VIII exhibit inactivating BK
      currents, K(V) currents, and low-frequency electrical resonance.
AB  - Outward K currents and electrical resonance of frog (Rana esculenta) saccular
      hair cells isolated enzymatically with bacterial protease VIII were investigated
      using the perforated patch-clamp method. Under voltage-clamp conditions we
      identified two K currents, a voltage-dependent K (K(V)) current, and a partially
      inactivating iberiotoxin-sensitive K (BK) current. The K(V) current activated at
      a membrane potential of approximately -50 mV (from a holding potential of -70
      mV). Its activation rate was rather slow, having a time constant in the range 5-8
      ms at 0 mV. The K(V) current was resistant to tetraethylammonium (10 mM), but was
      inhibited by 4-aminopyridine (1 mM). A striking feature of the BK current was its
      inactivation; this was monoexponential and had fast kinetics (tau(inact)=2.7 ms
      +/-1.2, at -10 mV; n=8). Inactivation of the current was incomplete, a residual
      sustained component remaining. This varied considerably among hair cells (mean
      ratio between peak transient and sustained component was 1.22+/-0.18, range 0.53
      1.8; n=8). In current-clamp mode steady depolarizing current pulses evoked
      membrane potential oscillatory responses, with mean frequencies varying between
      30 and 100 Hz for membrane potentials from -60 to -40 mV (n=18). Most hair cells
      (14/18) exhibited damped oscillations, and in the remainder a few initial damped
      oscillations were succeeded by smaller, undamped voltage oscillations. The peak
      quality factor and the characteristic frequency assessed on 14 cells displaying
      only damped oscillatory responses were 2.4+/-1.3 and 59+/-39 Hz, respectively. In
      contrast, papain-dissociated frog saccular hair cells possess solely a sustained
      BK current, and exhibited significantly higher resonant frequencies and quality
      factors. In conclusion, the K currents and the electrical resonance of hair cells
      dissociated in protease VIII differ markedly from those dissociated with papain,
      but are similar to those reported for in situ preparations, suggesting that our
      dissociation procedure preserves the electrophysiological profile of in situ frog
      saccular hair cells.

PMID- 12527124
TI  - Effects of salicylate on serotoninergic activities in rat inferior colliculus and
      auditory cortex.
AB  - In vivo microdialysis offers a unique approach to monitor biochemical events
      related to brain function and metabolism, and has been used extensively in many
      systems to measure the release of endogenous transmitters and other neuroactive
      substances during normal and pathological conditions. The characterization of
      neurotransmitters' changes induced by salicylate in the inferior colliculus (IC)
      and the auditory cortex (AC) may provide insight into the action of salicylate on
      the auditory system and, through this, provide a better understanding of
      neurological mechanism of salicylate-induced tinnitus. In the present study, the
      effect of salicylate on 5-HT system in IC and AC has been monitored by
      microdialysis in salicylate-induced tinnitus animal models. Glucose and lactate
      levels in IC and AC were significantly increased after application of salicylate
      (350 mg/kg, i.p.), indicating a salicylate-related increase in regional neuronal
      activity. The 5-HT level increased to a maximum of 268+/-27% basal level in IC 2
      h after application and of 277+/-24% basal level in AC around 3 h after
      application. These data suggest that the increases of 5-HT levels in IC and AC
      may be involved in the tinnitus generation.

PMID- 12527125
TI  - Mechanical leverage in the middle ear of the American bullfrog, Rana catesbeiana.
AB  - Textbooks lump the middle ears of 'submammalian Tetrapoda' as being 'one-ossicle
      ears'. Conventionally the anuran middle ear is depicted with a shaft-like
      skeletal unit connecting the tympanic membrane to the inner ear. This shaft
      comprises mediad a long bony columella and laterad a short cartilaginous
      extracolumella. But dissection of Rana catesbeiana ears showed: the
      extracolumella, as long as the columella, is proximally expanded in the vertical
      plane, forming dorsal and ventral heads. The medio-dorsal head is movably jointed
      to the columella, between these two there is an obtuse angle ventrad; the
      extracolumellar medio-ventral head is anchored by a ligament to the middle-ear
      cavity ceiling. When the tympanic membrane moves outwards, pulling the
      extracolumella, the medio-dorsal head of the extracolumella must be forced
      inwards, rotating on the ventral anchorage, pushing the columella towards the
      inner ear. The ossicular chain thus includes a mechanical lever, possessing the
      magnitude of the ratio length:width of the extracolumella; this is additional to
      the lever known from the columellar footplate, which rotates on its firm ventral
      attachment. These levers are confirmed physiologically, by the difference between
      the inner-ear sensitivity (shown by isopotential audiograms of microphonic
      potentials) when stimulated by a vibrator first at the tympanic membrane, then at
      the proximal stump of the amputated columella. Perusal of the primary literature
      showed that this morphology is widespread among anuran ears.

PMID- 12527126
TI  - Behavioural measurement of level-dependent shifts in the vibration pattern on the
      basilar membrane at 1 and 2 kHz.
AB  - Physiological data suggest that the peak of the travelling wave on the basilar
      membrane evoked by a high-frequency sinusoid moves towards the base with
      increasing level. Previously, we used a forward-masking technique to provide
      evidence for a similar effect in humans at 4 and 6.5 kHz. In the present study,
      we used a similar technique to determine whether level-dependent shifts occur for
      mid-range frequencies. The signal was a brief 1-kHz or 2-kHz tone presented at 10
      dB SL (approximately 30 dB SPL). For three fixed masker levels (75, 85 and 95 dB
      SPL), we measured the duration of the gap between the masker and signal required
      to give 79.4% correct detection of the signal (called the 'gap threshold') as a
      function of masker frequency; the longer the gap threshold, the more effective is
      the masker. The gap-threshold patterns nearly always showed a single peak close
      to the signal frequency. The gap-threshold patterns spread markedly towards lower
      frequencies with increasing masker level, but the frequency at the peak did not
      change systematically with level. We conclude that, for mid-range frequencies,
      the peak of the travelling wave does not shift significantly with increasing
      level over the range 30-95 dB SPL, but the envelope of the travelling wave
      becomes more shallow on its basal side.

PMID- 12527127
TI  - Effect of temporal separation on tone-sequence discrimination in monkeys.
AB  - Perception of auditory spectral-temporal patterns was examined in two Japanese
      monkeys. The stimuli used were pairs of pure tones of different frequencies that
      were presented sequentially. The monkeys were required to discriminate whether
      the frequency of the second tone was higher or lower than the first tone. The
      performances of the monkeys deteriorated when a temporal gap (i.e., silence) was
      inserted between the component tones. A comparison experiment did not show such
      effects in human participants. The results suggested that monkeys use frequency
      transitions for tone-sequence discrimination, and that local characters are more
      dominant discrimination cues in monkeys than in humans.

PMID- 12527128
TI  - An in vivo tracer study of noise-induced damage to the reticular lamina.
AB  - An in vivo tracer was used to determine if the reticular lamina and/or the cell
      membranes abutting the endolymphatic space are temporarily disrupted after
      intense noise exposure (4-kHz OBN, 108-dB SPL, 1.75 h). Using a double-barreled
      micropipette, the endolymphatic potential (EP) was recorded and artificial
      endolymph containing 10% carbon particles was injected into the endolymphatic
      space either 0 days or 28 days post-exposure. The cochleae were fixed 30-45 min
      post-injection, then dehydrated, embedded in plastic and dissected as flat
      preparations. Damage in the organ of Corti (OC) was quantified, the location of
      carbon was determined, and some OC segments were then sectioned radially. EP
      averaged 72+/-5 mV in five controls. These cochleae had carbon tracer in the
      endolymphatic space only. Four of five noise-exposed chinchillas examined 3-4 h
      post-exposure had a low EP (30+/-6 mV). The cochleae from these 0-day animals had
      several focal lesions in which nearly all outer hair cells had just degenerated.
      At these lesions, carbon was attached to cell membranes and debris between the
      reticular lamina and basilar membrane. By transmission electron microscopy,
      discontinuities were found in the apical membranes of sensory and supporting
      cells. Carbon particles were found in the cytoplasm of these cells. Four of five
      animals examined at 28 days had an average EP of 70+/-11 mV. The cochleae from
      these animals had multiple lesions in the basal turn, all of which were healed by
      phalangeal scars or squamous epithelial cells. In these cochleae, no carbon was
      found within the OC. Acute disruption of the reticular lamina and the apical
      membranes of sensory and supporting cells from noise appears to be a major
      mechanism to account for degeneration in the cochlea that spreads or continues
      for days to weeks post-exposure.

PMID- 12527129
TI  - Effects of age and cochlear damage on the metabolic activity of the avian
      cochlear nucleus.
AB  - Most aging commercially raised broiler chickens display a progressive loss of
      cochlear hair cells in a pattern similar to the cochlear degeneration found in
      aging humans: basal (high frequency) hair cells are affected first, followed by
      apical (low frequency) hair cells [Durham et al., Hear. Res. 166 (2002) 82-95].
      Here, cochlear anatomy was assessed from scanning electron micrographs. Then, the
      metabolic activity of cochlear nucleus (nucleus magnocellularis, NM) neurons in
      15-19, 30, 39, 40, and 65-66 week old broiler chickens was examined using
      cytochrome oxidase histochemistry and compared to the degree of cochlear
      abnormality. Cochleae of 15-19 week old birds are largely normal; therefore the
      level of NM metabolic activity is considered the baseline. Cochleae of the 30
      week old group display mild damage and hair cell regeneration in the base.
      Metabolic activity in rostral (high frequency) NM is increased relative to the
      baseline, while activity remains unchanged in caudal (low frequency) NM. The 39
      and 65-66 week old groups display severe and total damage extending into the apex
      of the cochlea. Metabolic activity is decreased in rostral and caudal NM at these
      ages. These results suggest that auditory central nervous system metabolism
      (cytochrome oxidase activity) is affected by changes in the aging chicken
      cochlea.

PMID- 12527130
TI  - Expanding the biological basis of tinnitus: crossmodal origins and the role of
      neuroplasticity.
AB  - Tinnitus is most often initiated by modality specific otopathologic disturbances
      affecting peripheral and central auditory pathways. However, there is growing
      evidence indicating that the anatomical location generating tinnitus occurs at
      sites different from the initial pathology. Support for this notion is found in
      individuals where tinnitus can be triggered or modulated by inputs from other
      sensory modalities or sensorimotor systems (somatosensory, somatomotor, visual
      motor). The use of functional imaging methods combined with psychophysics,
      detailed physical examinations and questionnaire-based assessments has reinforced
      and validated these observations. Available data suggest that tinnitus-related
      crossmodal interactions are more common than previously anticipated. This
      communication reviews these advancements and suggests that a relatively broad
      multimodal network of neurons is involved in generating and sustaining the
      tinnitus perception in some forms of the disorder. Also implicated as part of the
      tinnitus experience are interactions within large-scale neural networks
      subserving attention, cognition, and emotion. Incorporating this knowledge into
      contemporary psychophysiological models will help facilitate the
      conceptualization of this phantom perception in a more comprehensive manner.

PMID- 12527131
TI  - Mechanisms responsible for postnatal middle ear amniotic fluid clearance.
AB  - Neonatal guinea pigs show signs of a temporary conductive hearing loss during the
      first few days after birth. It has been suggested that this is due mainly to the
      presence of amniotic fluid in the middle ear (ME) cavity at birth and its
      subsequent clearance. This study was designed to try to identify the mechanisms
      responsible for the amniotic fluid clearance from the ME after birth by means of
      several experiments in guinea pigs. The osmolarity of the blood, amniotic fluid
      and the fluid in the ME cavity of guinea pig fetuses was measured. Serum and
      normal saline were introduced into the ME of older animals and fluid clearance
      was monitored short- and long-term by microscopic observation, tympanometry and
      estimation of residual fluid. Following instillation of 1/5 normal saline and
      normal saline into the ME cavity, the osmolarity of the remaining fluid was
      determined, short- and long-term. Clear osmotic pressure gradients were found
      between amniotic fluid (low pressure), fetal blood (higher pressure) and the
      fluid in the fetal ME (intermediate between them). The MEs into which normal
      saline had been introduced developed negative pressure and, over several days,
      were cleared of fluid. When serum was applied, ME pressure remained close to
      atmospheric and the fluid was not cleared. Hypotonic saline application led to an
      increase in the osmotic pressure in the fluid remaining in the ME. It is
      concluded that most of the amniotic fluid is cleared from the neonatal ME cavity
      by water outflow into the blood due to osmotic pressure gradients.

PMID- 12527132
TI  - Otoacoustic emissions and brainstem evoked potentials in compound carriers of
      connexin 26 mutations.
AB  - This study compares the effects of mutations in the gap junction protein connexin
      26 (Cx26), on outer hair cells (OHCs), inner hair cells (IHCs) and auditory
      nerve/brainstem among carriers of these mutations. One hundred and twenty eight
      individuals, from a village with widespread consanguinity and congenital
      deafness, due to three Cx26 mutations, were selected among relatives of deaf
      persons, and divided into non-carriers, carriers of one mutation, homozygous to
      one mutation, or compound heterozygous carriers of two different mutations.
      Distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses
      (ABRs) and audiometric evaluation were compared in these genetic groups. Hearing
      loss among homozygotes and compound heterozygotes was comparable and ranged from
      mild to profound. Most ABRs from these groups showed no responses or partial
      responses (peaks III, V) with prolonged latencies, but some individuals had all
      peaks at normal latencies. DPOAEs were absent, except sporadic responses.
      Carriers of one mutation had significantly smaller DPOAEs compared to non
      carriers, although normal pure tone audiograms and ABRs were found in these
      groups. In conclusion, based on DPOAEs, Cx26 mutations may impact OHC function
      among carriers of one or two Cx26 mutations. IHC/nerve impairment among
      homozygotes and compound heterozygotes is variable. OHCs may be more susceptible
      to Cx26 mutations compared to IHCs and the auditory nerve and brainstem pathway
      activated by them.

PMID- 12527133
TI  - Functional development of the auditory brainstem in the tammar wallaby (Macropus
      eugenii): the superior olivary complex and its relationship with the auditory
      brainstem response (ABR).
AB  - Twenty pouch-young tammar wallabies (Macropus eugenii) were used to determine the
      generator of the auditory brainstem response (ABR) during development through ABR
      and focal superior olivary complex (SO) recordings. A click response from the SO
      in the wallaby was recorded from postnatal day (PND) 112 when the ABR was only a
      positive-negative deflection. Before PND 120, the SO response did not contribute
      to the ABR as it occurred outside the ABR time-span. After PND 140, the SO
      response was correlated with multiple waves of the ABR with its dominant
      component corresponding to the ABR P3 wave. The latency, threshold, and amplitude
      of the SO response developed to the adult-like level at PND 140, while the rate
      following ability in the SO response reached the adult level at PND 160.
      Presumably this was due to more complicated mechanisms underlying the auditory
      adaptation. The adaptation of the SO response was directly proportional to the
      stimulus rate and intensity as well as developmental status. Developmental
      comparison between the ABR and the focal responses from four auditory brainstem
      nuclei indicated that each ABR component may have a dominant contributor from the
      auditory brainstem, but there was no simple and exclusive association between the
      ABR component and the auditory brainstem nuclei.

PMID- 12527134
TI  - Type 1 vanilloid receptor expression by mammalian inner ear ganglion cells.
AB  - The type 1 vanilloid receptor (VR1) is a non-specific cation channel activated by
      capsaicin, lipoxygenase (LOX) products, heat and acid. This study demonstrates
      VR1 and 5-LOX expression by inner ear ganglion cells. A PCR product (210 bp) was
      amplified from both oligo(dT)- and random primer-generated cDNAs of rat spiral
      ganglion cells using VR1 gene-specific primers constructed from the 3' non
      homologous region. This PCR product shared 100% sequence homology to a rat VR1
      cDNA (GenBank accession no. AF029310) and a rat vanilloid receptor splice variant
      mRNA (GenBank accession no. AF158248). Frozen sections of PLP-fixed, decalcified
      Long-Evans rat temporal bones were stained immunohistochemically for VR1. Neurons
      and satellite cells in both the vestibular and spiral ganglia were VR1
      immunopositive. Neurons and supporting cells in adjacent sections of these
      ganglia were immunopositive for 5-LOX. These findings raise the hypothesis that
      activation of VR1 by endogenous ligands may contribute to hypersensitivity of the
      eighth nerve to hair cell inputs in a variety of pathologic conditions, such as
      tinnitus, Meniere's disease and migraine. In particular, these data suggest that
      LOX activation during inflammatory processes or during cyclo-oxygenase inhibition
      (e.g. by aspirin) is a potential intrinsic source of VR1 activation in inner ear
      ganglia.

PMID- 12527135
TI  - Ultrasonic masker clarifies ultrasonic perception in man.
AB  - Bone conduction enables ultrasound to be heard. Although several hypotheses about
      ultrasonic perception have been presented, the perception mechanism of bone
      conducted ultrasound has not yet been established. In this study, to investigate
      ultrasonic perception, the amount of masking produced by 27-, 30- and 33-kHz bone
      conducted ultrasonic maskers for air-conducted high-frequency sounds was measured
      in the frequency range of 8-18 kHz at 1-kHz intervals. The results showed that
      the air-conducted signals in the frequency range of 10-14 kHz were strongly
      masked by the ultrasonic maskers. When the masker intensity increased from 5 to
      10 dB SL, the growth of masking was more than 10 dB in the frequency range of 9
      15 kHz, and the masking spread strongly to lower frequencies. Furthermore, the
      dynamic range for bone-conducted ultrasound was clearly narrower than that for
      air-conducted high-frequency sounds. These results suggest that perception of
      bone-conducted ultrasound depends on inner hair cell activity induced by
      ultrasound, even without modulation being present, and does not depend on
      enhancement by the outer hair cells in the basal turn of the cochlea.

PMID- 12527136
TI  - Auditory function associated with Col11a1 haploinsufficiency in chondrodysplasia
      (cho) mice.
AB  - Heterozygosity for mutations in the fibrillar collagen gene COL11A1 causes
      sensorineural hearing loss in patients with Stickler syndrome or Marshall
      syndrome. Chondrodysplasia (cho) is a functional null allele of Col11a1 that
      causes lethal chondrodysplasia in cho/cho newborn mice, and osteoarthritis in
      cho/+ heterozygotes. To determine if Col11a1 haploinsufficiency causes hearing
      loss in cho/+ mice, auditory brainstem response (ABR) thresholds were measured at
      2, 4, 6, 8 and 10 months of age. There was no difference in ABR thresholds for
      click and tone burst stimuli between cho/+ and +/+ mice at all ages. In contrast
      to the conclusion of a previous report, our results indicate that Col11a1
      haploinsufficiency does not cause significant hearing loss on the C57BL/6 strain
      background. We conclude that Stickler syndrome and Marshall syndrome mutations in
      COL11A1 cause hearing loss via dominant negative effects upon wild-type fibrillar
      collagen polypeptides in the extracellular matrices of the cochlea.

PMID- 12527137
TI  - Thyroid hormone is not necessary for the development of outer hair cell
      electromotility.
AB  - The outer hair cell (OHC), one of two receptor cell types in the organ of Corti,
      plays a critical role in mammalian hearing. OHCs enhance basilar membrane motion
      through a local mechanical feedback process within the cochlea, termed the
      'cochlear amplifier'. It is generally believed that the basis of cochlear
      amplification is a voltage-dependent electromotile response of OHCs. Measurements
      of electromotility in developing animals indicate that the onset of motility
      normally occurs around 7 days after birth in altricial rodents such as gerbils
      and rats. Thyroid hormone (TH) plays a crucial role in the development of the
      auditory system. Deficiency of the hormone between the late embryonic stage and
      the second postnatal week can cause severe hearing loss. Several studies suggest
      that TH deficiency might also affect the development of the cochlear amplifier.
      The goal of this study was therefore to examine whether TH was necessary for the
      development of OHC motility. The organ of Corti of gerbils was dissected out at
      birth and grown in culture with defined concentration of triiodothyronine (T3),
      the active ligand for the TH receptor. Motility was measured from OHCs isolated
      from 7-, 11- and 14-day-old cultures. Motility did indeed develop in OHCs
      deprived of normal concentration of T3. This suggests that the defective auditory
      function seen in TH-deficient animals is most likely due to morphological and
      physiological changes in the cochlea, rather than the motor function of the OHCs.

PMID- 12527138
TI  - Cochlear aqueduct flow resistance is not constant during evoked inner ear
      pressure change in the guinea pig.
AB  - Inner ear fluid pressure was measured during 6.25 mHz square wave middle ear
      pressure manipulation, with a perforated tympanic membrane. After a negative
      going middle ear pressure change the calculated flow resistance of the inner ear
      pressure release routes (mainly the cochlear aqueduct) was approximately
      constant, with a value of 12 Pa s/nl (averaged over two ears), when values for
      the inner ear window compliance are taken from the literature. After a positive
      going middle ear pressure change the calculated flow resistance changed with
      round window position and with the pressure difference across the cochlear
      aqueduct. It reached an average maximum value of 114 Pa s/nl. The change of flow
      resistance during inner ear pressure variation can be explained by a permeability
      change of the cochlear aqueduct, caused by a change of structures filling the
      aqueduct and its entrance in scala tympani.

PMID- 12527139
TI  - Electrode configuration influences action potential initiation site and ensemble
      stochastic response properties.
AB  - The configuration of intracochlear electrodes used to electrically stimulate the
      auditory nerve influences the ensemble fiber response. For example, monopolar
      stimulation produces lower thresholds and greater spread of excitation than does
      bipolar stimulation. We used two approaches to investigate how the ensemble of
      auditory-nerve fibers responds to stimulation delivered by different electrode
      configurations. As the electrically evoked compound action potential (ECAP)
      reflects the ensemble response of the nerve, we used its morphology and changes
      with stimulus level to assess issues related to site-of-excitation and fiber
      recruitment. In our first approach, feline ECAPs were obtained using a nucleus
      style banded electrode array. ECAP latency functions indicated that bipolar
      stimulation can initiate action potentials at more peripheral sites than does
      monopolar stimulation. We observed double-peaked ECAPs with bipolar and tripolar
      stimulation, suggesting excitation of both peripheral and central neural
      processes. Finally, we observed in some cases a tendency for monopolar
      stimulation to produce wider ECAP potentials, consistent with the notion that
      monopolar stimulation excites a broader spatial extent of the fiber population.
      In our second approach, we applied a simple model to published surveys of single
      fiber responses to provide insight into the stochastic properties of the ensemble
      response. Our results suggest that broader recruitment of fiber activity produced
      by monopolar stimulation results in a population response with more probabilistic
      response characteristics and ensemble spike jitter. These observations and our
      ECAP results are consistent with reports of perceptual advantages attributed to
      monopolar or other less-focused modes of stimulation.

PMID- 12527140
TI  - Effect of click intensity on click-evoked otoacoustic emission waveforms:
      implications for the origin of emissions.
AB  - The rather shallow growth of click-evoked otoacoustic emissions (CEOAE) with
      click intensity, namely <1 dB/dB, distinguishes genuine CEOAEs from stimulus
      artifacts, thereby providing the rationale for the popular 'derived nonlinear
      recording' method. However, other CEOAE nonlinearities regarding phase or
      envelope dependence on stimulus intensity have been barely acknowledged so far.
      The present work used CEOAEs from 20 normal ears recorded in response to 50-86 dB
      peak equivalent SPL clicks. The phases of CEOAE spectral components varied
      considerably with click intensity (sometimes more than 120 degrees ), mostly in a
      monotonic manner and in such a way that in the majority of ears, phase lagged
      with increasing intensity. When present, synchronized spontaneous otoacoustic
      emissions exhibited the same behavior. In a few instances, conspicuous frequency
      shifts of CEOAE spectral peaks were seen. In contrast to CEOAE phases, envelopes
      were almost intensity-invariant. This behavior contrasts with that of basilar
      membrane motion at the place tuned to the stimulus frequency, as consistently
      disclosed by several recent publications, i.e., no phase shift and large envelope
      shift with stimulus intensity. It is thought that the phase invariance of basilar
      membrane motion implies that whatever they do, outer hair cells cannot alter the
      resonance frequency of the cochlear partition. If one elaborates along this line
      of reasoning, the large phase shift of CEOAEs with click intensity implies that
      CEOAEs at frequency f cannot come from the place tuned to f and that instead,
      they may be intermodulation distortion products produced by nonlinear
      interactions between spectral components of the click stimulus over a significant
      length of the basilar membrane.

PMID- 12527141
TI  - Specific N-terminal CGRP fragments mitigate chronic hypoxic pulmonary
      hypertension in rats.
AB  - Chronic hypoxic pulmonary hypertension (HPH) is characterized by elevated
      pulmonary arterial pressure (P(PA)), right ventricular hypertrophy (RVH),
      pulmonary vascular remodeling, pulmonary edema and polycythemia. Currently, there
      is no safe and effective treatment for HPH. Calcitonin gene-related peptide
      (CGRP) is the most potent peptide vasodilator discovered thus far. We previously
      demonstrated that exogenous CGRP reversed HPH in rats. However, the CGRP1
      receptor antagonist CGRP(8-37) and smaller inhibitory C-terminal CGRP fragments
      that can be formed by enzymatic cleavage in vivo may compromise the beneficial
      effects of endogenous or exogenous CGRP. We here examine the agonistic efficacy
      of N-terminal rat alpha-CGRP peptides containing the disulfide bridge (Cys(2)
      Cys(7)) with amidated C-terminal in prevention of HPH. Chronic infusion of CGRP(1
      8), CGRP(1-13), or CGRP(1-14) at 7 nmol/h/rat via the right jugular vein during
      14 days of hypobaric hypoxia (10% inspired O(2)) significantly decreased the
      P(PA), RVH and pulmonary arterial medial thickness in comparison with controls,
      suggesting that these CGRP sequences can mitigate chronic HPH in rats. Systemic
      pressure was unchanged by infused peptides indicating no carry-over effect. In
      conclusion, N-terminal CGRP fragments (CGRP(1-8), CGRP(1-13) and CGRP(1-14)) may
      have a protective role in hypoxic pulmonary hypertension.

PMID- 12527142
TI  - Reciprocal paracrine pathways link atrial natriuretic peptide and somatostatin
      secretion in the antrum of the stomach.
AB  - Atrial natriuretic peptide (ANP) as well as its receptor, NPR-A, have been
      identified in gastric antral mucosa, suggesting that ANP may act in a paracrine
      fashion to regulate gastric secretion. In the present study, we have superfused
      antral mucosal segments obtained from rat stomach to examine the paracrine
      pathways linking ANP and somatostatin secretion in this region.ANP (0.1 pM to 0.1
      microM) caused a concentration-dependent increase in somatostatin secretion
      (EC(50), 0.3 nM). The somatostatin response to ANP was unaffected by the axonal
      blocker tetrodotoxin but abolished by addition of the selective NPR-A antagonist,
      anantin. Anantin alone inhibited somatostatin secretion by 18+/-3% (P<0.005),
      implying that endogenous ANP, acting via the NPR-A receptor, stimulates
      somatostatin secretion. Somatostatin (1 pM to 1 microM) caused a concentration
      dependent decrease in ANP secretion (EC(50), 0.7 nM) that was abolished by
      addition of the somatostatin subtype 2 receptor (sst2) antagonist, PRL2903.
      Neutralization of ambient somatostatin with somatostatin antibody (final dilution
      1:200) increased basal ANP secretion by 70+/-8% (P<001), implying that endogenous
      somatostatin inhibits ANP secretion. We conclude that antral ANP and somatostatin
      secretion are linked by paracrine feedback pathways: endogenous ANP, acting via
      the NPR-A receptor, stimulates somatostatin secretion, and endogenous
      somatostatin, acting via the sst2 receptor, inhibits ANP secretion.

PMID- 12527143
TI  - Somatostatin-induced gastric protection against ethanol: involvement of nitric
      oxide and effects on gastric mucosal blood flow.
AB  - BACKGROUND/AIMS: The mechanisms of somatostatin-mediated gastroprotection are not
      fully understood. Aims of this study were to determine in the rat the role of
      nitric oxide (NO) in somatostatin-induced effects on gastric mucosal protection
      and blood flow (GMBF) in the absence and in the presence of intraluminal ethanol.
      METHODS: Ethanol (70% v/v)-induced gastric mucosal injury after orogastric dosing
      was quantitated at 30 min and GMBF determined in an ex vivo gastric chamber
      preparation. RESULTS: Somatostatin (4 microg/kg; i.p.) protection against ethanol
      induced ulceration was prevented by the NO inhibitor L-NNA and restored by L
      arginine, but not D-arginine. Somatostatin (1-8 microg/kg; i.p.) did not effect
      basal GMBF. The gastroprotective dose of somatostatin (4 microg/kg; i.p.)
      prevented the decrease in GMBF caused by ethanol. L-NNA reversed this vascular
      effect of somatostatin. CONCLUSION: Somatostatin-induced gastroprotection and
      restoration of GMBF during ethanol exposure involve mechanisms which are
      dependent on NO generation.

PMID- 12527145
TI  - Muscle insulin binding and plasma levels in relation to liver glucokinase
      activity, glucose metabolism and dietary carbohydrates in rainbow trout.
AB  - Rainbow trout were fed for 10 weeks with either a carbohydrate-free diet (C-free)
      or with four experimental diets containing various levels (20 or 40%) and sources
      of starch (extruded wheat or peas) in order to examine metabolic utilisation of
      dietary vegetable carbohydrates and its endocrine control. The study was focused
      on the parameters described as limiting in glucose metabolism in fish. Feeding
      trials were conducted at 8 and 18 degrees C to establish whether carbohydrate
      rich diets can be used in trout farming irrespective of water temperature. At
      both temperatures, pea diets (especially the highest level) resulted in a feed
      efficiency as high as the C-free diet. Fish had similar growth rates except when
      fed the low wheat content diet. Glycaemia values 6 h after feeding were
      significantly higher in trout fed carbohydrate diets than those given the C-free
      diet, whereas plasma insulin levels were similar independently of the levels of
      dietary starch. This study provides the first evidence that glucokinase (GK)
      activity and mRNA level in trout liver increase in proportion to the content of
      dietary starch. Nevertheless, these changes were not correlated with plasma
      insulin levels. Insulin-like growth factor-I (IGF-I) binding and number of
      receptors in skeletal muscle were consistently higher than those for insulin but
      no diet-induced differences were found for any of these parameters. Temperature
      clearly affected the postprandial profile of glucose and insulin, which both
      showed lower levels 6 h after feeding at 8 degrees C than at 18 degrees C, which
      was consistent with a lower feed intake. Glucose and insulin levels decreased
      markedly 24 h after feeding at 18 degrees C, while they were still high at 8
      degrees C, an observation concordant with delayed transit rate. These findings
      indicate satisfactory adaptation of rainbow trout to diets with a relatively high
      vegetable starch content, especially when provided as extruded peas, and indicate
      that diets with increased levels of carbohydrates can be used in this species
      even when it is reared at low temperature.

PMID- 12527144
TI  - eNOS-dependent vascular interaction between nitric oxide and calcitonin gene
      related peptide in mice: gender selectivity and effects on blood aggregation.
AB  - The present study was performed to explore a possible vascular interplay between
      nitric oxide (NO) and calcitonin gene-related peptide (CGRP). We examined factors
      affecting CGRP release by the NO donor, nitroglycerin (NTG) and the potential
      involvement of endothelial NO synthase (eNOS) using eNOS knockout (-/-) vs. wild
      type (+/+) mice. In the female eNOS (+/+) mice, but not in males, in vitro NTG
      (0.73 mM) induced significant increases in the release of CGRP-like
      immunoreactivity (CGRP-LI) from the aorta and the heart but not from the small
      intestine. In eNOS (-/-) mice, NTG incubation did not induce any CGRP-LI changes
      in either gender. These results suggest that NTG-induced CGRP release is eNOS
      dependent and tissue- and gender-selective. The functional implication of this NO
      CGRP interaction was further examined by testing the anti-aggregatory action of
      acetylcholine (Ach). Ach-induced platelet inhibition was significantly enhanced
      by the addition of aorta segments of either gender. However, the female aorta
      segments exhibited a greater platelet inhibitory effect, which could be reversed
      by the blockade of either CGRP or eNOS. Our study revealed a novel eNOS-dependent
      interaction between NO and CGRP, and the possible participation of regulatory
      peptides in affecting platelet function and possibly cardiovascular protection in
      females.

PMID- 12527147
TI  - Stages of change and fluid intake in dialysis patients.
AB  - Nutrition professionals constantly strive to improve adherence to dietary
      recommendations in hemodialysis patients. The purpose of this study was to
      evaluate the effects of a 12-week intervention based on stages of change to
      decrease fluid gain in dialysis patients. Readiness to change, knowledge of
      appropriate weight gain, and mean weight gains were obtained from patients in
      five intervention (n=216) and five control (n=100) dialysis units. Intervention
      had more participants in the maintenance and precontemplation stages at the end
      of the intervention (P=0.001) compared to the control group. Knowledge scores
      significantly increased in the intervention group (P<0.001) during the course of
      the intervention. However, fluid gains did not decrease in either group. Although
      this intervention did not produce behavior change, the results can aid other
      educators in planning intervention programs for renal failure and other chronic
      diseases.

PMID- 12527148
TI  - Evaluation of the impact of a pharmaceutical care program in children with
      asthma.
AB  - The objective of this study was to evaluate the impact of a pharmaceutical care
      program on children with asthma. A comprehensive asthma education and monitoring
      program that includes basic asthma knowledge, symptoms and exacerbation
      evaluation, pharmacotherapy assessment including inhaler technique, and quality
      of life measurements was developed and applied in an outpatient paediatric clinic
      of the Catholic University of Chile. All patients with moderate asthma scheduled
      for outpatient visits with their internist over a 1-year period were referred for
      pharmacist intervention. Patients (aged 7-17) with moderate asthma attending the
      clinic were allocated to the intervention (group A) or control group (group B).
      Intervention patients were educated on their disease, pharmacotherapy, self
      management, and inhalation techniques. The group B were children with their
      regular treatment for asthma but without pharmaceutical intervention. A
      paediatric asthma quality of life questionnaire (PAQLQ) was applied to both
      groups at 0, 2, and 9 weeks to assess the quality of life. Spirometry was done at
      the beginning and at the completion of the 9-week study. Beta-agonists used by
      each patient were also recorded. Eleven children (10.0+/-0.7 years) were included
      in the pharmaceutical care program, and ten children (9.9+/-0.6 years) in group
      B. For the individual domains of activities (A), emotions (E), and symptoms (S)
      there was a significant improvement in the children who received pharmaceutical
      care in comparison with those who did not receive it. The scores of group B did
      not change during the 9 weeks of follow-up. There were no significant changes in
      spirometric values in either group.

PMID- 12527149
TI  - Educational diagnosis of self-management behaviors of parents with asthmatic
      children by triangulation based on PRECEDE-PROCEED model in Taiwan.
AB  - This assessment study is an educational and behavioral diagnosis based on the
      PRECEDE-PROCEED model which identifies factors (predisposing, enabling, and
      reinforcing) that must be changed to initiate and sustain the self-management
      behaviors of parents with asthmatic children (aged 3-14 years) in the largest
      children's hospital in northern Taiwan. In the first step, 21 self-management
      behaviors were induced from the content analysis of qualitative interviews of 16
      successful parents. The construct validity of 21 self-management behaviors was
      established by principal component factor analysis, followed by the rotation
      method with Varimax and Kaiser normalization. Three extracted components were
      named: preventing behaviors, managing behaviors, and assessing behaviors. The
      cumulative percentage of variance of the three factors was 48.2%. In order to
      identify the determinate factors of self-management behaviors, 133 parents with
      asthmatic children were recruited and investigated at the outpatient department
      of the hospital, in the second step. All the instruments were developed based on
      the results of content analysis from an in-depth interview. The results indicated
      that the self-management behaviors of this group were middle level. Stepwise
      multiple regression was used to analyze the predicted rate of self-management
      behaviors by 12 educational factors. The results indicate that self-efficacy,
      perceived effectiveness, and children's cooperation can explain 50.2% of the
      variance in the self-management behaviors. The determinate factors of preventive
      behaviors were self-efficacy, perceived effectiveness, and children's cooperation
      with R(2)=0.448. The determinate factor of managing behaviors was perceived
      effectiveness with R(2)=0.262. The determinate factors of assessing behaviors
      were perceived severity, knowledge, self-efficacy, and perceived effectiveness
      with R(2)=0.311. These results suggest the direction of a self-management
      education program for different parents of asthmatic children with poor
      management skills. Future research should be conducted to evaluate the
      effectiveness of treatment by a more specific self-management education program,
      which focuses on increasing self-efficacy and perceived effectiveness.

PMID- 12527150
TI  - The effect of an intervention programme to improve health education leaflet
      uptake and distribution in community pharmacies.
AB  - The effect of an intervention programme to improve health education leaflet
      uptake in community pharmacies was conducted with a small convenience sample of
      12 community pharmacies in North Staffordshire, UK. The intervention consisted of
      four different modes of leaflet provision. Modes 1 and 2 (without and with overt
      offer of advice from pharmacist respectively) relied upon the pharmacy client to
      actively obtain a leaflet, whereas Modes 3 and 4 (without and with offer of
      advice from pharmacist respectively) relied upon pharmacy staff to actively
      provide a leaflet. All 12 community pharmacies received 50 copies of a
      purposefully designed leaflet. The intervention extended over one calendar month.
      Data was collected during the intervention via monitoring forms completed by the
      pharmacist on a day to day basis, and interviews were conducted with the
      pharmacists at the end of the study. The overall uptake or distribution rate of
      leaflets was 64%. In both modes which offered advice (Modes 2 and 4),
      approximately one of every five leaflet recipients sought advice. The community
      pharmacists considered the intervention to be feasible, effective and enabled the
      utilisation of their skills.

PMID- 12527151
TI  - Feasibility of implementation of a Dutch smoking cessation and relapse prevention
      protocol for pregnant women.
AB  - A cross-sectional design was used to asses whether Dutch midwives trained to use
      a smoking cessation counseling protocol appreciated it and could implement it in
      routine care. Midwives received a questionnaire after the implementation period
      of the effectiveness study was finished. In total, 118 midwives from 42 practices
      participated in the study, 69 midwives (58.5%) returned the questionnaire. To
      validate the results collected among midwives, clients who participated in the
      study were also questioned about the information they received about smoking
      cessation from their midwife. Experimental midwives more often reported giving
      the advice to quit (B=0.50, S.E.=0.24, P<0.05), setting a quit date with clients
      who indicated to be motivated to quit (B=1.69, S.E.=0.28, P<0.001) and discussing
      aftercare (B=1.10, S.E.=0.25, P<0.001). These results were confirmed by data
      collected among clients. This easy-to-implement program is recommended for broad
      dissemination. Further investigation is needed to improve the partner and
      postpartum component.

PMID- 12527152
TI  - The construction of the gendered patient: hospital staff's attitudes to female
      and male patients.
AB  - This article presents an analysis of some of the gendered attitudes to male and
      female patients as expressed by a variety of hospital staff, such as physicians,
      nurses and nursing aides of both sexes. Through unstructured interviews, we
      attempted to capture the staff's descriptions of female and male patients.
      Analysis and interpretation was based on an analytic framework of symbolic
      interaction where perception of patient as gendered was seen as negotiated
      through interactions between the health care worker and the patient. All staff,
      independent of their own gender, describe differences between female and male
      patients. Despite some differences between professional positions, all describe
      female patients as more demanding than male. Physicians describe elderly female
      patients in particular, as being demanding, while nursing staff say younger women
      are most demanding.

PMID- 12527153
TI  - The self-regulation of fatigue and associated complaints: an exploratory
      simulation.
AB  - A computer simulation has been developed that reflects the microdynamics of
      dealing with fatigue and associated complaints. The theoretical base was derived
      from Leventhal, Nerenz and Steele's self-regulation model; the empirical base
      from a large-scale diary study carried out over a period of 3 weeks. The
      simulation results demonstrate that the process of self-regulation is non-linear.
      Consequently, some patient education assumptions are challenged: that individuals
      suffering from fatigue and associated complaints are likely to follow a similar
      trajectory, that interventions should not be started until after a 6 weeks delay,
      and that an intervention always produces the same results. These insights may be
      generalised to other health complaints that have no medical explanation.

PMID- 12527154
TI  - Multimodal patient education program with stress management for childhood and
      adolescent asthma.
AB  - The present study aimed to evaluate a multimodal patient education program
      carried out during inpatient rehabilitation. The program included cognitive
      behavioral stress management training as a main component. The efficacy was
      examined in comparison to an education program without stress management. In
      total N=68 patients aged between 8 and 16 years were included in the post
      treatment and N=46 patients in the 6 months follow-up assessment. Short- and long
      term intervention effects of the multimodal education program were observed in
      relation to patients' age. The experimental treatment elicited significant
      improvements in adaptive coping in adolescents aged from 14 to 16 years. In
      contrast, substantial effects were not yielded for the control treatment. The
      results suggest that the multimodal patient education training has beneficial
      effects on stress management in adolescents with asthma. Results are discussed
      with regard to predictive factors for rehabilitation outcome.

PMID- 12527155
TI  - Non-consensual sex experienced by men who have sex with men: prevalence and
      association with mental health.
AB  - Little is known about the psychosocial factors associated with sexual assault
      experienced by males. Men (N=358), 19-35 years of age, recruited by community
      outreach, completed questionnaires. Eligibility criteria included: being HIV
      negative and self-identifying as gay or bisexual. Lifetime prevalence rates of
      childhood sexual abuse, juvenile prostitution, and adult sexual assault were
      determined. The mental health of this population was explored including
      associations between sexual victimization and mental health disorders (alcohol
      abuse, suicidal ideation and attempts, mood disorders, and poor self-esteem).
      Almost 1 in 10 of the men had engaged in juvenile prostitution, 14% were forced
      into sexual activity before 14 years of age, and 14% were sexually victimized
      after the age of 14. Those exposed to non-consensual sex were 2.9 (95% CI: 1.8
      4.7) times more likely to abuse alcohol than those free of victimization. Those
      who reported childhood sexual abuse were 3.3 (95% CI: 1.7-6.4) times more likely
      to have attempted suicide. Juvenile prostitution was associated with current
      depression (OR=6.4; 95% CI: 2.8-14.9). Health professionals have the
      responsibility to respond competently and sensitively to victims of sexual
      violence. To do this, many need to recognize the prevalence of male sexual
      trauma, to deconstruct their personal beliefs about same-sex sexual violence, and
      to learn to ask sensitive questions in their assessment interviews.

PMID- 12527156
TI  - Practical clinical behavioral treatment of obesity.
AB  - The objective was to create a method/model that works in practical clinical
      treatment for health care personnel as well as for the patients, to educate and
      supervise health care staff according to this model and to initiate long-term
      treatment of obese patients in a health care setting. The hypothesis was that it
      is possible to successfully initiate behavior-modified treatment in the form of a
      structured treatment program as a method and a tool adapted to use in health
      care. The aim of this article is to describe an extensive structural cognitive
      behavioral treatment program for patients. The treatment program is documented in
      a handbook for supervisors and a self-monitoring book for patients. This handbook
      is used in the education of the health care personnel and supports the supervisor
      in the clinical work with the patients. The main purpose of all individual or
      group treatment is to bring about reduction of body weight or weight control. To
      obtain weight control through lifestyle changes a balance has to be found between
      eating behavior, physical activity and body weight control. To reach this kind of
      balance it is important to have treatment programs where the aim and goals are
      clearly declared. The structure and the content of the program shall motivate and
      create interest for changes in the overweight person's behavior. This treatment
      program includes a schematic survey and an example of a structured treatment
      program. Over the last few years, 850 nurses, dietitians and other health care
      personnel have been educated, representing 400 primary health care centers and
      hospitals within Sweden. Overall these participants find their education and
      supervision meaningful and valuable.

PMID- 12527157
TI  - Knowledge and attitudes of Israeli high school pupils towards alternative
      medicine.
AB  - One hundred ninety-seven high school students were examined concerning their
      knowledge and attitudes towards complementary and alternative medicine (CAM). The
      students attended the 9-12th grades. The score level of the pupils' knowledge was
      quite satisfactory (67%). The knowledge didn't change during the 4 years of high
      school attendance and was not correlated with the pupils' grades or the socio
      economic status (SES) data. The majority of the pupils showed positive attitudes
      towards the topics and treatment methods of CAM. The pre-existence of chronic
      diseases in the family and experience of family members with CAM had a positive
      influence upon pupils' attitudes. The principal sources of knowledge concerning
      CAM were the media (TV, radio and newspapers) and other acquaintances' experience
      with CAM. Sixty-nine percent of the pupils expressed their willingness to attend
      formal lessons and instruction about CAM in school. Our suggestion is to teach
      these topics formally in school with professional instructors (physicians and/or
      academic healers) during biology lessons.

PMID- 12527158
TI  - Does smoking affect the outcome of patient education and self-management in
      asthmatics?
AB  - Information on the potential effect of smoking on the outcome of patient
      education in asthma is lacking. We randomly allocated 78 asthmatics to either a
      control or intervention group. Intervention consisted of two 2-h group sessions
      followed by 1-2 individual sessions each by a nurse and a physiotherapist. Self
      management was emphasised following a stepwise treatment plan at exacerbations.
      Smokers experienced more general practitioner (GP) visits (P=0.001) and
      absenteeism from work (P=0.02), a greater need for rescue medication (P=0.03), a
      larger drop in FEV1 (P=0.02) and worse St. George's respiratory questionnaire
      (SGRQ) scores (P<0.001) compared to non-smokers during the 1-year follow-up. In
      multiple linear and logistic regression models smoking was still associated with
      worse SGRQ scores, a drop in FEV1, higher need for GP visits and rescue
      medication and higher total costs. We, thus, conclude that smoking was associated
      with reduced health related quality of life, a drop in FEV1, increased need for
      rescue medication and GP visits and higher costs after patient education during
      the 1-year follow-up, compared to no smoking.

PMID- 12527159
TI  - Effect of enhancers and retarders on percutaneous absorption of flurbiprofen from
      hydrogels.
AB  - The effect of enhancers/retarders on the transdermal absorption of flurbiprofen
      from cellulose hydrogels was studied in vitro. The release rate of flurbiprofen
      and the viscosity of hydrogel matrices were also examined. The flux of
      flurbiprofen from cellulose hydrogels approximated that from aqueous buffers,
      whereas the skin reservoir of flurbiprofen was lower with hydrogels.
      Incorporation of the cosolvents, propylene glycol (PG) and ethanol, did not
      significantly increase skin absorption of flurbiprofen. Ethanol even reduced the
      skin reservoir of the drug. Oleic acid, an unsaturated fatty acid, produced the
      largest skin reservoir of the drug when incorporated into the hydrogels. D
      Limonene, a cyclic monoterpene, showed the greatest ability to enhance the flux
      of flurbiprofen. However, phospholipids as retarders markedly reduced the skin
      absorption of flurbiprofen. The mechanisms by which enhancers/retarders govern
      flurbiprofen permeation were elucidated by in vitro permeation studies using
      various skin types (enhancers/retarders-pretreated skin, stratum corneum (SC)
      stripped skin, and delipidized skin) and histological examination. The results
      suggest different mechanisms and skin structural modifications caused by
      different enhancers/retarders.

PMID- 12527160
TI  - Surface modification of poly(lactic acid) nanoparticles by covalent attachment of
      thiol groups by means of three methods.
AB  - The aim of the present work was to find a suitable method for the introduction of
      thiol functions on the surface of poly(DL-lactic acid) (PLA) nanoparticles. Three
      different approaches were investigated. The modification of the surface involves
      the activation of PLA carboxylic acid groups followed by the attack of a
      nucleophile such as cysteine (method #1) or cystamine (method #2 and #3) that
      provide thiol functions via an amide bond. For the conjugation with cystamine, a
      second reaction step is required to expose the sulfhydryl function of cystamine
      that is otherwise protected in a disulfide bond. 1,4-Dithio-DL-threitol (DTT)
      (method #2) or Tris(2-carboxyethyl)-phosphine hydrochloride (method #3) were
      evaluated for their ability to reduce this linkage. Method #1 allowed a maximum
      of 8.5+/-2.8 mmol of thiol functions per mol of PLA to be attached on the surface
      of the nanoparticles. Method #2 allowed the introduction of a greater number of
      thiol functions (up to 190+/-15 mmol per mol of PLA). However, this latter method
      has a major drawback: DTT interacts strongly with the nanoparticle matrix during
      the reduction step. Method #3 has the advantage over method #2 in that it allowed
      a significant number of thiol functions to be covalently bound to the particles
      (up to 107.6+/-0.6 mmol per mol of PLA) without the problem of undesired
      interaction between DTT and the nanoparticle matrix. The introduction of thiol
      groups onto the surface of PLA nanoparticles is possible with all three suggested
      methods. The method #3 provides a straight forward approach for the substitution
      of carboxylic acid groups with a high number of activated sulfhydryl at the
      surface of PLA nanoparticles.

PMID- 12527161
TI  - Dissolution and assaying of multicomponent tablets by chemometric methods using
      computer-aided spectrophotometer.
AB  - Dissolution of three component tablets containing paracetamol (APAP),
      propyphenazone (PP), and caffeine (CAF) was carried out by USP paddle method.
      Three chemometric methods; inverse least square (ILS), principal component
      regression (PCR) and partial least squares (PLS) were applied to simultaneous
      assay of APAP, PP and CAF in tablets. The PCR, PLS and ILS methods were applied
      to simultaneous dissolution APAP, PP and CAF in tablets using a double beam UV
      Vis spectrophotometer without any chemical separation and any graphical treatment
      of the overlapping spectra of three drugs. Twenty two mixture solutions in
      different concentrations were prepared in simulated gastric juice (SGJ, USP) for
      the chemometric calibrations as training set. The absorbance data matrix was
      obtained by measuring the absorbance at 14 wavelength points (from 222.5 to 292.5
      nm) with the intervals of 5 nm (Deltalambda=5 nm) in the spectral region between
      200 and 310 nm. Training set and absorbance data were used for the calibrations
      of chemometric methods. The developed calibrations were tested for the previously
      prepared solutions of mixture of three drugs for the validation of the assay
      method. The chemometric calculations were performed by using the 'MAPLE VRSQUO;
      software. The results of three chemometric methods were statistically compared
      with each other. These chemometric calibrations were successfully applied to the
      content uniformity and dissolution of the multicomponent tablets without any
      separation procedure. The synthetic mixtures of three drugs were used for the
      validity of the calibrations. Means recoveries (percent) and relative standard
      deviation of PLS, PCR and ILS methods were found to be 100.1+/-0.6, 101.4+/-1.6
      and 100.1+/-0.6 for APAP; 100.9+/-3.2, 102.0+/-3.3 and 100.9+/-3.2 for PP; 99.9+/
      3.5, 101.6+/-3.3 and 99.9+/-3.2 for CAF, respectively. Dissolution profiles of
      three component tablets were performed. More than 95% of drugs were dissolved
      within 15 min. All of the three-chemometric methods in this study can be
      satisfactorily used for the quantitative analysis and for dissolutions test of
      multicomponent dosage form.

PMID- 12527162
TI  - Bioavailability and efficacy characteristics of two different oral liquid
      formulations of albendazole.
AB  - The oral bioavailability and anthelmintic efficacy in mice of a new formulation
      of albendazole (ABZ) dissolved in a solution of hydroxypropyl-beta-cyclodextrin
      (HPCD) are compared with a conventional ABZ suspension of carboxymethylcellulose.
      Plasma concentrations of ABZ and albendazole sulphoxide (ABZ-SO), its active and
      main metabolite, were assayed by HPLC. The AUC(0- infinity ) and C(max) values
      obtained for both ABZ and ABZ-SO, after administration of the ABZ-HPCD solution
      were significantly higher (P<0.01) than those obtained from the ABZ suspension.
      Although, the differences between the ABZ and ABZ-SO-T(max) values were found not
      to be significant, regardless of the formulation. The anthelmintic activities
      against enteral (pre-adult) and parenteral (migrating and encysted larvae) stages
      of Trichinella spiralis were studied in mice. The ABZ solution was more efficient
      against pre-adult and encysted larvae than the ABZ suspension. The efficacy
      differences between both formulations against the migrating larvae, were found to
      be not significant (P<0.05). For the migrating parasite stage, there was a linear
      correlation between the anthelmintic activity and pharmacokinetical parameters
      with respect to the ABZ-AUC(0- infinity ) value. Meanwhile, for the muscular
      encysted parasite stage, better relationships were obtained for AUC(0- infinity )
      and C(max) values from ABZ-SO, which had correlation coefficients of 0.996 and
      0.987, respectively.

PMID- 12527163
TI  - The enhancement effect of surfactants on the penetration of lorazepam through rat
      skin.
AB  - Lorazepam is an anxiolytic, antidepressant agent, having suitable feature for
      transdermal delivery. The percutaneous permeation of lorazepam was investigated
      in rat skin after application of a water:propylene glycol (50:50%v/v). The
      enhancing effects of various surfactants (sodium lauryl sulfate (SLS),
      cetyltrimethylammonium bromide (CTAB), benzalkonium chloride or Tween 80) with
      different concentrations on the permeation of lorazepam were evaluated using
      Franz diffusion cells fitted with rat skins. Flux, K(p), lag time and enhancement
      ratios (ERs) of lorazepam were measured over 24 h and compared with control
      sample. Furthermore, lorazepam solubility in presence of surfactants was
      determined. The in vitro permeation experiments with rat skin revealed that the
      surfactant enhancers varied in their ability to enhance the flux of lorazepam.
      The permeation profile of lorazepam in presence of the cationic surfactant, CTAB,
      reveals that an increase in the concentration of CTAB results in an increase in
      the flux of lorazepam in comparison with the control. But an increase in
      concentration of CTAB or benzalkounium chloride from 0.5 to 1% w/w or from 1 to
      2.5% w/w resulted in a reduction in ER, respectively. Benzalkonium chloride which
      possessed the highest lipophilicity (logP=1.9) among cationic surfactants
      provided the greatest enhancement for lorazepam flux (7.66-fold over control) at
      1% w/w of the surfactant. CTAB (logP<1) and sodium lauryl sulphate at a
      concentration of 5% w/w (the highest concentration) exhibited the greatest
      increase in flux of lorazepam compared with control (9.82 and 11.30-fold,
      respectively, over control). This is attributed to the damaging effect of the
      cationic and anionic surfactants on the skin at higher concentration. The results
      also showed that the highest ER was obtained in presence of 1% w/w surfactant
      with the exception of SLS and CTAB. The increase in flux at low enhancer
      concentrations is normally attributed to the ability of the surfactant molecules
      to penetrate the skin and increase its permeability. Reduction in the rate of
      transport of the drug present in enhancer systems beyond 1% w/w is attributed to
      the ability of the surfactant molecules to form micelles and is normally observed
      only if interaction between micelle and the drug occurs.

PMID- 12527164
TI  - Release of albumin from chitosan-coated pectin beads in vitro.
AB  - The release behavior of albumin from chitosan-coated pectin beads in vitro was
      investigated. The factors, such as concentration of CaCl(2), molecular weight of
      chitosan, pH of chitosan solution, and pH of release medium, which can have a
      significant effect on the release behavior from the beads, were discussed in this
      study. The loading efficiency (LE) of albumin showed maximum value when the
      concentration of CaCl(2) and the weight ratio of pectin to albumin were 2 wt.%
      and 2, respectively. The release of albumin from pectin beads could be retarded
      by coating with chitosan at various pH medium. The increase of the concentration
      of CaCl(2) induced the decrease of albumin release for uncoated-pectin beads, but
      not much difference of release for coated-pectin ones. The higher molecular
      weight of chitosan showed less albumin release than the lower one. The release of
      albumin from the chitosan-coated pectin beads was dependent on pH of coating
      solution and release medium, which might affect the degree of swelling of pectin
      beads.

PMID- 12527165
TI  - Evaluation of solid dispersion particles prepared with SEDS.
AB  - Formation of solid solution particles in the Solution Enhanced Dispersion by
      Supercritical fluids (SEDS) process from a model drug and two different types of
      carriers, mannitol and Eudragit E100 was evaluated. The crystal properties of
      samples and molecular interactions were investigated with DSC and FTIR,
      respectively. The effect of co-crystallisation of drug and mannitol on
      dissolution rate was studied. Even if a true one-phase solid dispersion was not
      obtained, the crystal structure of both drug and mannitol was mutually affected
      by the presence of the other. The drug was not in highly crystalline form in the
      co-precipitates. The interactions between the drug and mannitol could also be
      identified as hydrogen bonding between the amine or hydroxyl groups of the drug
      and the hydroxyl groups of mannitol. These interactions and changes in the
      crystal structure are probably directly related to the increase in the
      dissolution rate observed. A true solid solution was obtained when the drug was
      co-processed with Eudragit E100. A clear interaction between the acid hydroxyl
      group of the drug and the basic carbonyl group on the Eudragit E100 was observed.
      SEDS was shown to be an effective process for forming intimate blends and solid
      solutions for the drug and two different types of carriers.

PMID- 12527166
TI  - Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin
      against Mycobacterium avium complex infection in human macrophages.
AB  - Cyclodextrins and liposomes have been used in recent years as drug delivery
      vehicles, improving the bioavailability and therapeutic efficacy of many poorly
      water-soluble drugs. In this study, we used two approaches to enhance the
      availability of the poorly water-soluble antibiotic, clarithromycin, by inclusion
      complex formation and by liposome-encapsulation. We examined the efficacies of
      these formulations against Mycobacterium avium complex (MAC) in human peripheral
      blood monocyte-derived macrophages. The water solubility of clarithromycin was
      enhanced by about 700-fold by complexation with cyclodextrin. The use of a rapid
      radiometric (BACTEC) method for the detection of MAC growth and susceptibility
      showed identical MICs against MAC for both the free and complexed drug. The anti
      MAC efficacy of the cyclodextrin complex of clarithromycin in macrophages was
      slightly lower than the free drug, probably due to the high stability of the
      inclusion complex. At higher drug concentrations, Liposome-encapsulated
      clarithromycin was slightly more effective against intracellular MAC growth than
      the free drug.

PMID- 12527167
TI  - Influence of multiple nasal administrations of bioadhesive powders on the insulin
      bioavailability.
AB  - Peptides and more especially insulin are mainly used in therapies that need
      multiple drug administration. As peptides are highly potent, it is required that
      their bioavailability remains constant even during a long term administration. In
      this study, the bioavailability and blood glucose levels are reported after
      multiple nasal administration of insulin via two bioadhesive platforms consisting
      of a cospray dried mixture of Amioca starch and Carbopol 974P (1/3) and a
      physical mixture of drum dried waxy maize starch and Carbopol 974P (9/1),
      respectively. The experiments were performed in rabbits and the formulations were
      administered during 8 consecutive days. The bioavailability and the maximal
      decrease of the blood glucose level were determined on the first and last day of
      the insulin administration. These two parameters were decreased on the eighth day
      compared with the first day of administration. When the formulations were not
      administered from day 2 until day 7, the bioavailability on the eighth day
      compared with the first day of administration was not modified. It was concluded
      that daily administrations of the bioadhesive formulations affected the nasal
      bioavailability of insulin in rabbits.

PMID- 12527168
TI  - Effect of iontophoresis on transcorneal permeation 'in vitro' of two beta
      blocking agents, and on corneal hydration.
AB  - Purpose of the present investigation was to examine the effect of iontophoresis
      on permeation of two beta-blocking agents, timolol maleate (TM) and betaxolol
      hydrochloride (BX) across rabbit corneas in vitro. Continuous or pulsed current
      of variable intensity and duration was applied, and possible corneal damage due
      to the electric treatment was assessed by measuring the corneal hydration level.
      The effect of iontophoresis on corneal permeation of the relatively more
      hydrophilic TM was much greater than the effect on the more lipophilic BX. It was
      found that for both drugs the iontophoretically driven transcorneal penetration
      is governed only by current density and overall time of treatment, irrespective
      of the type of treatment (single or repeated) and of current (constant or
      pulsed). For both drugs all significant permeation increases due to iontophoresis
      were invariably accompanied by a significant increased corneal hydration,
      indicative of damage to the corneal epithelium. Even if the present in vitro data
      cannot be extrapolated to an in vivo treatment, they confirm the potential risk
      associated with ocular iontophoresis.

PMID- 12527169
TI  - Biphasic drug release from film-coated tablets.
AB  - A study was carried out into the biphasic drug release properties of film-coated
      paracetamol tablets. The tablet cores were formulated without a disintegrant and
      film-coated with a coating formulation consisting of pectin, chitosan and
      hydroxypropylmethylcellulose in a ratio of 6:1:0.37. The tablet cores and the
      film-coated tablets with coat weight gains (CWGs) of 6, 9 and 13% were evaluated
      for their water absorption (swelling) and drug release properties. All the
      tablets absorbed water from pH 6.0 Sorensen's phosphate buffer and the amount of
      water absorbed increased with an increase in tablet CWG. The addition of 100
      microl/50 ml pectinolytic enzymes to the medium resulted in at least a 40%
      reduction in the amount of water absorption by the tablets, as compared to the
      medium without enzymes. When the enzyme concentration was increased to 200
      microl/50 ml, there was a further reduction ( approximately 8% w/w) in the amount
      of water absorbed by the tablets. Drug release was controlled in upper
      gastrointestinal fluids and decreased with an increase in tablet CWG. Drug
      release was, however, accelerated in the presence of pectinolytic enzymes,
      consistent with the entry of the tablets in the colon. An evaluation of the drug
      release data by the Korsmeyer-Peppas equation showed the involvement of molecular
      diffusion and other factors such as film/tablet erosion and drug dissolution in
      drug release.

PMID- 12527170
TI  - BCNU-loaded poly(D, L-lactide-co-glycolide) wafer and antitumor activity against
      XF-498 human CNS tumor cells in vitro.
AB  - Implantable polymeric device that can release chemotherapeutic agent directly
      into central nervous system (CNS) has had an impact on malignant glioma therapy.
      The purpose of our study was to develop an implantable polymeric device, which
      can release intact 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for long-term
      period over 1 month, and to evaluate its cytotoxicity against XF 498 human CNS
      tumor cells in vitro. BCNU was incorporated into biodegradable poly(D,L-lactide
      co-glycolide) (PLGA), by using spray-drying method. BCNU-loaded PLGA
      microparticles were characterized by scanning electron microscopy (SEM), powder X
      ray diffraction, and differential scanning calorimetry. SEM observation of the
      microparticles showed that the microparticles were spherical, i.e. microspheres.
      Homogeneous distribution of BCNU in PLGA microsphere was confirmed by significant
      reduction of crystallinity of BCNU. Microspheres were fabricated into wafers with
      flat and smooth surface by direct compression method. In vitro release of BCNU in
      pH 7.4 phosphate buffered saline was prolonged up to 8 weeks after short initial
      burst period. Antitumor activity of BCNU-loaded PLGA wafer against XF 498 human
      CNS tumor cells continued over 1 month and, PLGA only did not affect the growth
      of the cells. Meanwhile, the cytotoxic activity of BCNU powder disappeared within
      12 h. These results strongly suggest that the BCNU/PLGA formulations increase
      release period of carmustine in vivo and also be useful in the development of
      implantable polymeric device for malignant glioma.

PMID- 12527171
TI  - Pharmacokinetics and antitumor effects of vincristine carried by microemulsions
      composed of PEG-lipid, oleic acid, vitamin E and cholesterol.
AB  - In this study, injectable microemulsions of vincristine (M-VCR) were prepared and
      its pharmacokinetics, acute toxicity and antitumor effects were evaluated. In M
      VCR, the surfactants were PEG-lipid and cholesterol, the oil phase was a vitamin
      E solution of oleic acid and VCR. The particle size distribution and zeta
      potential of M-VCR were measured by the laser light dynamic scattering method.
      The VCR-loading efficiency was measured by Sephadex G50 column chromatography.
      The stability of M-VCR was monitored by particle size, VCR-loading efficiency and
      VCR content changes of M-VCR stored at 7 degrees C. The pharmacokinetics, acute
      toxicity and antitumor effects of M-VCR were studied in C57BL/6 mice bearing
      mouse murine histocytoma M5076 tumors. When stored at 7 degrees C in the dark for
      1 year, the average diameter and VCR-loading efficiency of M-VCR changed from
      138.1+/-1.2 nm and 94.6+/-4.7% to 127.1+/-2.4 nm and 91.3+/-4.8% (n=3),
      respectively, while 7.4+/-0.3% VCR decomposition was observed (n=3). The plasma
      AUC of M-VCR was significantly greater than that of free VCR (F-VCR). The heart,
      spleen and liver AUC(0.08-12 h) of M-VCR were significantly smaller than those of
      F-VCR while the kidney AUC(0.08-12 h) of M-VCR was significantly greater than
      that of F-VCR. The tumor AUC(0.08-12 h) of M-VCR was significantly greater than
      that of F-VCR. M-VCR had lower acute toxicity and greater potential antitumor
      effects than F-VCR in M5076 tumor-bearing C57BL/6 mice. M-VCR is a useful tumor
      targeting microemulsion drug delivery system.

PMID- 12527172
TI  - Polymeric nanoparticle composed of fatty acids and poly(ethylene glycol) as a
      drug carrier.
AB  - Diamine-terminated poly(ethylene glycol) (ATPEG) was hydrophobically modified
      with long-chain fatty acids (FAs) through a coupling reaction using N,N'
      dicyclohexyl carbodiimide (DCC). FA-PEG-FA conjugates have different physico
      chemical properties according to the chain length of the fatty acid (FA).
      Synthesized FA-PEG-FA conjugate was confirmed by Fourier transform-infrared (FT
      IR). Since FA-PEG-FA conjugates have the amphiphilic characteristics in aqueous
      solution, polymeric nanoparticles of FA-PEG-FA conjugates were prepared using a
      simple dialysis method in water. The results of 1H nuclear magnetic resonance
      (NMR) spectroscopy and fluorescent spectroscopy suggest that the FA-PEG-FA
      conjugate has a typical core-shell type nanoparticle structure made by a self
      assembling process. From the analysis of fluorescence excitation spectra,
      especially, the critical micelles concentration (CMC) of this conjugate was
      changed unpredictably, i.e. the critical association concentration (CAC) value
      was decreased below a FA carbon number of 16 but, above increased a FA carbon
      number of 16. Transmission electron micrograph readings showed the spherical
      morphologies of the polymeric nanoparticles. The particle size was continuously
      decreased until below a FA carbon number of 20, but it was increased above a FA
      carbon number of 20. Clonazepam (CNZ), as a model drug, was easy to entrap into
      polymeric nanoparticles of the FA-PEG-FA conjugates. The drug release behavior
      was changed according to the FA chain length and was mainly diffusion controlled
      from the core portion.

PMID- 12527173
TI  - Planar gamma scintigraphy--points to consider when quantifying pulmonary dry
      powder aerosol deposition.
AB  - Methodological aspects of planar gamma scintigraphy used to quantify pulmonary
      aerosol deposition were investigated using an experimental dry powder
      formulation. Particles of micronized salbutamol sulphate were labelled with
      technetium-99m and admixed to an ordered mixture of unlabelled micronized
      salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was
      administered to 24 healthy subjects, 12 in each of two consecutive, similarly
      designed studies. Pulmonary deposition was determined using two methods: repeated
      planar imaging, and pharmacokinetic assessments following charcoal co
      administration to prevent gastrointestinal salbutamol absorption. After due
      consideration had been taken to ensure appropriate radiolabelling, image
      acquisition and processing procedures, a scintigraphic estimate of 26.2% (24.2
      28.4%) was obtained, which did not significantly differ from the pharmacokinetic
      estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the
      radiolabelling technique, quality control of radioaerosols produced during the
      study, correction for re-distribution of radiolabel from the lungs, selection of
      regions of interest, assessment of lung contours, correction for tissue
      attenuation of gamma rays and establishment of the actual recovery of
      radioactivity in the scintigraphic measurements could potentially affect the
      accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should
      be carefully considered in the design or evaluation of any such study.

PMID- 12527174
TI  - Preparation and evaluation of a liposomal formulation of sodium cromoglicate.
AB  - Sodium cromoglicate (SCG) is given by inhalation in prophylactic control of
      asthma. It was encapsulated in liposomes with a view to improve utilization of
      the drug when given via pulmonary route. The liposomes were characterized for
      encapsulation efficiency, shape, size and release rate. Liposomal dispersions
      were freeze-dried using a cryoprotectant. Freeze-dried liposomal dispersion
      retained 60% of drug upon reconstitution but increase in size of liposomes was
      noted. Liposomes exhibited good keeping properties when stored at 4 degrees C. In
      vivo performance of liposomal SCG was evaluated in sensitized guinea pigs. In one
      of the studies, differential leukocyte count and total leukocyte count in
      bronchoalveolar lavage fluid was measured. Liposomal dispersion showed
      significant inhibition of influx of neutrophils as compared with drug solution at
      24 h. However, in the second study, when recovery period required by animal to
      revert back to normal respiratory pattern from the onset or preconvulsion time
      was measured, no significant difference was found between drug solution and
      liposomal dispersion when administered 2 h before allergen challenge.

PMID- 12527176
TI  - Matrix formation in sustained release tablets: possible mechanism of dose
      dumping.
AB  - Conditions under which poly(ethyl acrylate, methyl methacrylate) 2:1 (poly(EA
      MMA), Eudragit NE) forms a stable matrix were investigated in tablets with
      diclofenac sodium (DS) as an active substance. DS was granulated with the aqueous
      polymer dispersion. Granules and/or tablets were cured under various temperature
      and humidity conditions. A six position rotating disk (200 rpm) apparatus was
      used for the release studies conducted in 37 degrees C acid then phosphate buffer
      (0.4 M) pH 6.8 or buffer only as the dissolution media. Morphological
      characteristics of the tablet surface were observed under SEM. Changes in tablet
      structure upon curing were evaluated through changes in tablet mechanical
      characteristics. Modulus of rupture, Young's modulus, AUC, AUC(<max), AUC(>max),
      where AUC=AUC(<max)+AUC(>max), were determined by the three-point bending test.
      Some poorly cured tablets dose-dumped when placed directly into buffer but not if
      first placed in acid and then buffer. A higher content of polymer in the matrix,
      led to formation of a stronger polymer network upon higher curing temperature
      and/or longer curing duration, whereas relative humidity had a minor effect.

PMID- 12527175
TI  - Release of recombinant human bone morphogenetic protein 2 from a newly developed
      carrier.
AB  - After implantation of a polymer-coated gelatin sponge (PGS) containing either 0.4
      or 1.0 mg of 125I-rhBMP-2 for each 1 cm(3) of PGS into the right ulnar of
      rabbits, changes in the level of radioactivity at the implant site and in the
      blood were measured for 21 days after implantation, and the cumulative excretion
      ratio of radioactivity in the urine and feces was calculated. For both doses,
      radioactivity at the implant site was eliminated biphasically. The concentration
      of trichloroacetic acid (TCA)-precipitable radioactivity in the blood reached a
      maximum 6 h after implantation, at which time it was equivalent to 1.41% of the
      administered dose (0.4 mg/cm(3)). The remaining radioactivity was eliminated
      rapidly thereafter, falling below the detection limit within 48 h. The
      t(1/2alpha) was about 0.1 days, the t(1/2beta) was about 3 days, and the mean
      resident time (MRT) value was about 4 days. By 17 days after implantation, 88.1%
      of the administered radioactivity had been excreted in the urine, and 1.7% had
      been excreted in the feces. TCA precipitation test results indicated that most of
      the radioactivity excreted in urine was a low-molecular weight decomposition
      product. At 21 days after implantation, the radioactivity of the PGS implant site
      had declined to 0.5% of the administered amount. Autoradiographs of the implant
      site taken 28 days after implantation revealed that, at both doses, the residual
      radioactivity was confined to the area of the implanted PGS. These results
      indicate that PGS retains an appropriate amount of recombinant human bone
      morphogenetic protein 2 (rhBMP-2) at the orthotopically implanted site for at
      least 21 days enough to induce bone regeneration. Thus, PGS shows great clinical
      potential as a carrier for rhBMP-2.

PMID- 12527177
TI  - Physicochemical characterization of solid dispersion of furosemide with TPGS.
AB  - The D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used to
      increase the aqueous solubility and dissolution rate of furosemide. The solid
      dispersion of furosemide with TPGS was prepared by solvent method using methanol.
      The aqueous solubility and the dissolution rate of furosemide were rapid and
      markedly enhanced from the 1:2 furosemide-TPGS solid dispersion. The X-ray
      diffractometry showed that pure furosemide and furosemide contained within the
      physical mixture were crystalline in nature, whereas furosemide in the solid
      dispersion was not in crystalline form. The infrared spectroscopic analysis
      showed that an interaction, in the solid dispersion, such as an association
      between the functional groups of furosemide and TPGS might occur in the molecular
      level. The infrared spectroscopy and differential thermal analysis showed the
      physicochemical modifications of the furosemide from the solid dispersion. The
      solid dispersion technique with TPGS provides a promising way to increase the
      solubility and dissolution rate of poorly soluble drugs.

PMID- 12527178
TI  - Influence of formulation parameters on gadolinium entrapment and tumor cell
      uptake using folate-coated nanoparticles.
AB  - Emulsifying wax and polyoxyl 2 stearyl ether (Brij 72) nanoparticles (2 mg/ml)
      containing high concentrations of gadolinium hexanedione (GdH) (0-3 mg) have been
      engineered from oil-in-water microemulsion templates. Solid nanoparticles were
      cured by cooling warm microemulsion templates (prepared at 55 degrees C) to room
      temperature in one vessel. Nanoparticles were characterized by transmission
      electron microscopy (TEM), photon correlation spectroscopy (PCS) and gel
      permeation chromatography (GPC). To obtain folate-coated nanoparticles, a folate
      ligand was added to either the microemulsion templates or nanoparticle
      suspensions at 25 degrees C. Since the concentration of Gd in the tumor is
      critical to the success of Gd-neutron capture therapy (NCT), the effects of
      various formulation factors on GdH entrapment in nanoparticles as well as tumor
      targeting were studied. GdH entrapment in nanoparticles was affected mostly by
      the method of GdH incorporation and surfactant concentration used in preparing
      the microemulsion templates. Cell uptake studies were carried out in KB cells
      (human nasopharyngeal epidermal carcinoma cell line). The method of adding folate
      ligand to the formulations did not significantly affect nanoparticle cell uptake
      (P>0.11; t-test). However, the concentration of folate ligand added to
      nanoparticles had the greatest influence on nanoparticle uptake (P<0.01; t-test).
      The results showed that GdH entrapment and cell uptake were optimized and
      suggested that engineered folate-coated nanoparticles may serve as effective
      carrier systems for Gd-NCT of tumors.

PMID- 12527179
TI  - A new stressed test to predict the foreign matter formation of minodronic acid in
      solution.
AB  - A formulation containing 0.5 mg/ml minodronic acid, 40 mM citrate, pH 4.5, and
      sodium chloride, stored in regular flint glass ampoules, was stable without
      particulate increase under high temperature conditions, such as 40 degrees C for
      6 months, or 50 or 60 degrees C for 3 months. However, when stored at 25 degrees
      C, there was an increase in >or=2 microm particles at the 5-month timepoint. This
      demonstrated that long-term stability cannot simply be predicted by the
      evaluation of samples just stored at higher temperatures. Therefore, a new
      stressed test was designed which is useful in the rapid selection of formulations
      that are stable and without particulate increase. Since the particulate matter is
      apparently a complex of minodronic acid and aluminum ions leaching from ampoules,
      samples were placed at 80 degrees C for up to 4 weeks to accelerate aluminum
      leaching. Although no particulate increase was observed directly after storage at
      80 degrees C, 4 freeze-thaw cycles following the storage caused a drastic
      particulate increase. The evaluation of samples subjected to the freeze-thaw
      cycles indicated that the following formulation modifications have inhibitory
      effects on particulate generation: (1). addition of meglumine, diethanolamine,
      mannitol, or glycerol to the formulation; (2). increase of citric acid
      concentration; (3). decrease of minodronic acid concentration. These
      modifications also worked well for samples stored at 25 degrees C for 6 months,
      and particulate increase did not occur. This method is a powerful tool for
      predicting the stability of minodronic acid in solution.

PMID- 12527180
TI  - Effects of citicholine and dimethylsulfoxide on transepithelial transport of
      passively diffused drugs in the Caco-2 cell culture model.
AB  - The objective of this study was to determine, using a Caco-2 cell monolayer
      model, the extent to which the paracellular and transcellular routes are altered
      by citicholine (CDP-Ch) and DMSO in the presence of human serum albumin (HSA).
      The apparent permeability (Papp) of mannitol in the presence of 4% (w/v) HSA was
      investigated using 0, 0.5, 1.0, 2.5, 5.0, and 10.0% (v/v)) of DMSO. The Papp for
      mannitol ranged from 0.56 x 10(-6) to 0.89 x 10(-6) cm/s (mean 0.77 x 10(-6)).
      Increasing the concentration of DMSO does not appear to have an effect on the
      paracellular transport of mannitol and on the transepithelial resistance (TEER)
      of the monolayer, (P>0.05). The effect of citicholine (CDP-Ch) was investigated
      in confluent Caco-2 cell monolayers incubated in the presence of 2, 4, 10, 40,
      60, 100 and 200 mM CDP-Ch at 37 degrees C in an atmosphere of 7% CO(2) and 95%
      relative humidity. Papp of mannitol and diltiazem in the presence of CDP-Ch
      ranged from 0.53 x 10(-6) to 8.52 x 10(-6) cm/s and from 1.30 x 10(-5) to 2.71 x
      10(-5) cm/s, respectively. CDP-Ch may have an effect on the stability of the
      tight junction complex resulting in an increase in the apparent permeability of
      mannitol.

PMID- 12527181
TI  - Effect of the biologically active fragment of zonula occludens toxin, delta G, on
      the intestinal paracellular transport and oral absorption of mannitol.
AB  - OBJECTIVE: Many therapeutically active agents experience low bioavailability upon
      oral administration due to low permeability, low solubility, interaction with
      efflux transporters or first pass metabolism. In general, absorption enhancers
      are agents that can modulate the paracellular permeability of drugs, thus,
      potentially increasing oral bioavailability. The objective of this study was to
      examine the effect of the active fragment of Zonula occludens toxin (Zot),
      deltaG, on the transport of a paracellular marker, mannitol, using in vitro (Caco
      2 cell monolayers) and in vivo (intraduodenal administration in rats)
      experimental methods. METHODS: The transport of [14C]mannitol with deltaG (0, 50,
      80, or 100 microg/ml) was determined across Caco-2 cells. Male Sprague-Dawley
      rats were assigned to receive one of the following treatments: [14C] mannitol (40
      microCi/kg), [14C]mannitol/deltaG (417 microg/kg), or [14C]
      mannitol/deltaG/Protease inhibitors (PI). RESULTS: The mean (+/-S.E.M.) apparent
      mannitol permeability coefficients (P(app)) observed after incubation with 0, 50,
      80, and 100 microg/ml deltaG were 3.5 (+/-0.4), 4.17 (+/-0.27), 4.33 (+/-0.61),
      and 9.94 (+/-0.24)x10(-6) cm/s. After oral administration, C(max) (3.8 x 10(-4)
      vs. 4.4 x 10(-4) mM) and AUC(0-6 h) (0.096 vs. 0.088 mM min), obtained for
      [14C]mannitol and [14C]mannitol/deltaG, respectively, were not statistically
      different. However, both C(max) (7.6 x 10(-4) mM) and AUC(0-6 h) (0.25 mM min)
      were significantly higher for the [14C]mannitol/deltaG/PI treatment. CONCLUSIONS:
      The 12 kDa fragment of Zot, deltaG, enhanced the in vitro transport and oral
      absorption of the paracellular marker, mannitol, in the presence of protease
      inhibitors (PI).

PMID- 12527182
TI  - Development of oral acetaminophen chewable tablets with inhibited bitter taste.
AB  - Various formulations with some matrix bases and corrigents were examined for
      development of oral chewable tablets which suppressed the bitter taste of
      acetaminophen, often used as an antipyretic for infants. Corn starch/lactose,
      cacao butter and hard fat (Witepsol H-15) were used for matrix bases, and
      sucrose, cocoa powder and commercial bitter-masking powder mixture made from
      lecithin (Benecoat BMI-40) were used for corrigents against bitter taste. The
      bitter taste intensity was evaluated using volunteers by comparison of test
      samples with standard solutions containing quinine at various concentrations. For
      the tablets made of matrix base and drug, Witepsol H-15 best inhibited the bitter
      taste of the drug, and the bitter strength tended to be suppressed with increase
      in the Witepsol H-15 amount. When the inhibitory effect on the bitter taste of
      acetaminophen solution was compared among the corrigents, each tended to suppress
      the bitter taste; especially, Benecoat BMI-40 exhibited a more inhibitory effect.
      Further, chewable tablets were made of one matrix base and one corrigent, and of
      one matrix base and two kinds of corrigents, their bitter taste intensities after
      chewing were compared. As a result, the tablets made of Witepsol H-15/Benecoat
      BMI-40/sucrose, of Witepsol H-15/cocoa powder/sucrose and of Witepsol H
      15/sucrose best masked the bitter taste so that they were tolerable enough to
      chew and swallow. The dosage forms best masking bitter taste showed good release
      of the drug, indicating little change in bioavailability by masking.

PMID- 12527183
TI  - Preparation of a copoly (dl-lactic/glycolic acid)-zinc oxide complex and its
      utilization to microcapsules containing recombinant human growth hormone.
AB  - A procedure to prepare a complex of copoly (dl-lactic/glycolic acid) and zinc
      oxide (PLGA-zinc oxide complex) was developed. Out of sparingly water-soluble
      zinc compounds, zinc oxide was most remarkably soluble in a PLGA/dichloromethane
      solution and the dissolution rates became faster as the water contents in the
      PLGA/dichloromethane solutions increased. Since the solubility of zinc oxide was
      saturated at approximately 0.5-fold molar ratio to PLGA and water was generated
      with dissolution of zinc oxide in the PLGA/dichloromethane solutions, it is
      suggested that zinc oxide interacts with the terminal carboxyl group of PLGA. In
      addition, the glass-transition temperature of a solid material obtained by vacuum
      drying the PLGA/dichloromethane solution dissolving zinc oxide became higher as
      the zinc content increased, suggesting that the formation of a PLGA-zinc oxide
      complex. Microcapsules were prepared with the PLGA-zinc oxide complex using
      recombinant human growth hormone (rhGH) in order to evaluate an effect of the
      complex on protein release and stability of protein in the microcapsules.
      Released rhGH amount from the microcapsules prepared with the PLGA-zinc oxide
      complex after subcutaneous administration in rats was significantly larger than
      that from microcapsules prepared with PLGA alone, indicating that rhGH molecules
      in the microcapsules was stabilized by the PLGA-zinc oxide complex.

PMID- 12527184
TI  - Non-surfactant nanospheres of progesterone inclusion complexes with amphiphilic
      beta-cyclodextrins.
AB  - Amphiphilic beta-cyclodextrins were formulated as nanospheres and characterised
      by particle size, zeta potential and TEM following freeze-fracture. The
      nanospheres were loaded with progesterone with different loading techniques
      involving the spontaneous formation of nanospheres from pre-formed inclusion
      complexes of amphiphilic beta-cyclodextrins modified on the primary or secondary
      face with progesterone. Inclusion complexes were characterised with various
      techniques including Differential Scanning Calorimetry (DSC), Fast Atom
      Bombardment Mass Spectrometry (FAB MS) and 1H NMR spectroscopy; and progesterone
      was believed to be partially included in the CD cavity. Loading properties of
      conventionally-loaded nanospheres were compared with those prepared directly from
      pre-formed inclusion complexes and loading technique was found to enhance
      associated drug percentage significantly (P<0.05). Although both amphiphilic beta
      cyclodextrins (6-N-CAPRO-beta-CD and beta-CDC6) were capable of high progesterone
      loading, beta-CDC6 displayed slightly higher entrapment efficiency due to the
      possible higher affinity of progesterone to the 14 alkyl chains surrounding this
      molecule resulting in higher drug adsorption to particle surface. Progesterone
      was released within a period of 1 h from all formulations. Progesterone-loaded
      amphiphilic beta-CD nanospheres were proved to be a promising non-surfactant
      injectable delivery system providing high-quantity of water-insoluble
      progesterone rapidly within 1 h.

PMID- 12527185
TI  - Adsorbed pluronics on the skin of human volunteers: effects on bacterial
      adhesion.
AB  - An amphiphilic copolymer, Pluronic F127, has been deposited, by adsorption, to
      the skin of human volunteers and the ability of the coated skin to resist
      bacterial colonisation has been evaluated. In parallel, the ability of the same
      copolymer to act as a bacterial release agent has been evaluated. In both cases,
      F127 proved to be of little added value in formulations designed to suppress the
      bacterial colonisation of human skin.

PMID- 12527186
TI  - Characterization of solid dispersions of itraconazole and
      hydroxypropylmethylcellulose prepared by melt extrusion--Part I.
AB  - Solid dispersions containing different ratios of itraconazole and
      hydroxypropylmethylcellulose (HPMC) were prepared by solvent casting. Based on
      dose, differential scanning calorimetry and dissolution results, a drug/polymer
      ratio of 40/60 w/w was selected in order to prepare dispersions by melt
      extrusion. The melt extrusion process was characterized using a design of
      experiments (DOE) approach. All parameter settings resulted in the formation of
      an amorphous solid dispersion whereby HPMC 2910 5 mPas prevents re
      crystallization of the drug during cooling. Dissolution measurements demonstrated
      that a significantly increased dissolution rate was obtained with the amorphous
      solid dispersion compared to the physical mixture. The outcome of DOE further
      indicated that melt extrusion is very robust with regard to the itraconazole/HPMC
      melt extrudate characteristics. Stability studies demonstrated that the
      itraconazole/HPMC 40/60 w/w milled melt extrudate formulation is chemically and
      physically stable for periods in excess of 6 months as indicated by the absence
      of degradation products or re-crystallization of the drug.

PMID- 12527187
TI  - The preparation and characterisation of drug-loaded alginate and chitosan
      sponges.
AB  - Sponges composed of sodium alginate and chitosan were prepared via a freeze
      drying process in order to assess the utility of mixed sponges as potential wound
      dressings or matrices for tissue engineering. Sponge preparation involved
      dissolving both polymers (either individually or mixed) in 1% acetic acid and
      freeze-drying the corresponding solutions. The mechanical properties of the
      sponges were assessed using texture analysis and the microstructure examined
      using scanning electron microscopy. The dissolution of a model drug (paracetamol)
      from the sponges was assessed as a function of polysaccharide composition. It was
      noted that the sponges had a flexible yet strong texture, as assessed
      macroscopically. Measurement of the resistance to compression ('hardness')
      indicated that the chitosan sponges were the 'hardest' while the alginate sponges
      showed the least resistance to compression, with all sponges showing a high
      degree of recovery. In contrast, the breaking force (tensile force) of the
      sponges were greatest for the single component systems, while the elongation
      prior to breaking was similar for each material. SEM studies indicated that the
      mixed systems had a less well-defined microstructure than the single component
      sponges. This was ascribed to the two polysaccharides interacting in aqueous
      solution via coulombic forces, leading to a more randomly ordered network being
      formed on freezing. Dissolution studies indicated that systems containing
      chitosan alone showed the slowest release profile, with the mixed systems showing
      a relatively rapid dissolution profile. The use of chitosan and alginates
      together, therefore, appears to allow the formulator to manipulate both the
      mechanical properties and the drug release properties of the sponges.

PMID- 12527188
TI  - Influence of enteric citric acid on the release profile of 4-aminopyridine from
      HPMC matrix tablets.
AB  - A weakly basic experimental drug, 4-aminopyridine (4-AP), was taken as a model to
      study the influence of enteric citric acid (ECA) on the release profile from
      hydroxypropyl methylcellulose (HPMC) matrices, to set up a system bringing about
      gradual release of the drug. For this purpose, powder mixtures were wet
      granulated with water and compressed with a hydraulic press at 55 MPa.
      Dissolution studies were made using first 900 ml HCl 0.1 N, and then phosphate
      buffer pH 7.4. Dissolution curves were described by M(t)/M(inf)=kt(n). As
      physically expected, increasing proportions (2-9%) of the in acid insoluble ECA
      decreased the release rate. In an acid medium, ECA acts as a physical barrier
      obstructing the diffusion path, dissolving after the pH change to 7.4. Both
      circumstances flattening the release profile. Apparent zero order release was
      observed at ECA concentrations of about 10%. The presence of ECA compensates the
      effect of decreased solubility of 4-AP at pH 7.4. Unexpectedly, higher ECA
      proportions (10-50%) act increasing the dissolution rate. This is attributed to a
      void space formation around the insoluble ECA, after HPMC hydration, which
      percolates after a critical ECA proportion of approximately 10%. Moreover,
      decreasing release constant values (k) show a logarithmic relationship with
      increasing values of the exponent (n). This indicates that an apparent zero-order
      release can be obtained at a given release constant.

PMID- 12527189
TI  - Sucrose cocoate, a component of cosmetic preparations, enhances nasal and ocular
      peptide absorption.
AB  - Sucrose cocoate (SL-40), an emulsifier employed in emollient, skin-moisturizing
      cosmetic formulations, contains a mixture of sucrose esters of coconut fatty
      acids in aqueous ethanol solution. In order to determine its potential utility in
      enhancing nasal and ocular drug delivery, absorption studies were performed in
      anesthetized Sprague-Dawley male rats with calcitonin and insulin, two distinct
      therapeutic peptides. Administration of a nasal insulin formulation containing
      0.5% sucrose cocoate caused a rapid and significant increase in plasma insulin
      levels, with a concomitant decrease in blood glucose levels. When insulin was
      administered ocularly in the presence of 0.5% sucrose cocoate, a smaller increase
      in plasma insulin levels, and a decrease in blood glucose levels, were observed.
      Administration of a nasal calcitonin formulation containing 0.5% sucrose cocoate
      caused a rapid increase in plasma calcitonin levels and a concomitant decrease in
      plasma calcium levels. Mass spectrometric analyses were used to characterize the
      nature of the sucrose fatty acid esters in the mixture. The most abundant sucrose
      ester in sucrose cocoate was sucrose monododecanoate, with smaller amounts of
      sucrose monodecanoate and sucrose monotetradecanoate. In vivo experiments
      confirmed that this ester was an effective enhancer of nasal peptide drug
      absorption.

PMID- 12527190
TI  - Enhanced stability of rubbery amylose-rich maize starch films plasticized with a
      combination of sorbitol and glycerol.
AB  - Well known aging problems with rubbery starch films are the migration of
      plasticizer and increased crystallinity leading to embrittlement. The effects of
      a combination of sorbitol and glycerol used as plasticizers on mechanical,
      moisture permeability and solid-state properties of rubbery amylose maize starch
      (Hylon VII) films were studied. The films were prepared by casting and were
      exposed to conditions of 25 degrees C/60% relative humidity (RH) and 40 degrees
      C/75% RH for 9 months. The starch films plasticized with a combination of
      sorbitol and glycerol (1:1) at equal amount to the polymer weight, were shown to
      be the most stable alternative of the studied films during the 9 months storage
      period. The water vapor transmission (WVTR) of the films did not change during
      the period of storage and neither did the elongation at break, but the tensile
      strength increased. X-ray diffraction (XRD) results showed that during storage no
      crystallization had occurred. The combination of sorbitol and glycerol prevented
      the migration of the plasticizer molecules out of the film.

PMID- 12527191
TI  - Structural organization of the sea urchin DNA (cytosine-5)-methyltransferase gene
      and characterization of five alternative spliced transcripts.
AB  - Sea urchin DNA (cytosine-5)-methyltransferase (Dnmt1) that is responsible for
      maintenance of DNA methylation patterns clearly shares similarity with various
      Dnmt1s identified in vertebrates. In this study, we determined the structure of
      the sea urchin Dnmt1 gene by screening a genomic library of the sea urchin
      Paracentrotus lividus with the complementary DNA (cDNA) as probe. Analysis of the
      positive clones demonstrated that the Dnmt1 gene consists of 34 exons and 33
      introns spanning a distance of 35 kb. All exon-intron junction sequences agree
      with the GT/AG consensus with the exception of the 3' acceptor site of intron 8
      where CT replaces AG consensus. The differences in the total number of exons
      between sea urchin and mouse genes reside mainly in the N-terminal region of the
      protein (exons 5-7 of the sea urchin, exons 5-12 of the mouse) where there is
      very low similarity in the amino acid sequence. By reverse transcription
      polymerase chain reaction using oligonucleotides spanning different regions of
      the cDNA we carried out a comprehensive analysis of alternative splicing of the
      Dnmt1 messenger RNA (mRNA) in sea urchin embryos at different stages of
      development. We demonstrated the presence of at least five alternative spliced
      mRNAs that are regulated during development and are translated in truncated or
      deleted proteins.

PMID- 12527192
TI  - Expression, alternative splicing and haplotype analysis of transcribed testis
      specific protein (TSPY) genes.
AB  - Testis specific protein (TSPY) is a human Y-chromosome derived gene with numerous
      functional and non-functional copies. Specific expression patterns in testis and
      testicular tumors, as in prostate cancer samples and cell lines led to the
      postulation of a potential role in cell proliferation, supported by the presence
      of a suppressor of variegation, enhancer of zeste and Trithorax/nucleosome
      assembling protein (nucleosome assembly protein) domain in the mature protein.
      Expression studies have now identified two transcripts of variable length, termed
      TSPY-S and -L, which differ in their 3'-translated region due to alternative
      splicing, and in the quantitative level of transcripts, with TSPY-S being at
      least 3-4-fold more abundant. In immunoblot experiments on human testis and LNCaP
      protein extracts using an anti-peptide-antiserum against the TSPY-L specific C
      terminus TSPY-L was characterized as a functional variant on the protein level.
      As there are at least three intragenic positions differing between various TSPY
      genes and thus defining certain haplotypes, the alternatively spliced TSPY
      transcripts were analysed for their haplotypes in order to link them to well
      defined TSPY loci. Surprisingly, no evidence of a G-G-18 haplotype was found for
      the TSPY-L transcript, while this haplotype makes up almost 50% of all TSPY-S
      transcripts. This excludes the corresponding TSPY-1 locus from alternative
      splicing. The only significant differences between the TSPY-1 locus and eight
      other loci were identified in the promotor region as revealed by detailed
      sequence comparisons. Thus one might speculate that the alternative splicing
      could be influenced by elements binding to the promotor region.

PMID- 12527193
TI  - Mammalian Crumbs3 is a small transmembrane protein linked to protein associated
      with Lin-7 (Pals1).
AB  - Drosophila Crumbs is a transmembrane protein that plays an important role in
      epithelial cell polarity and photoreceptor development. Overexpression of Crumbs
      in Drosophila epithelia expands the apical surface and leads to disruption of
      cell polarity. Drosophila Crumbs also interacts with two other polarity genes,
      Stardust and Discs Lost. Recent work has identified a human orthologue of
      Drosophila Crumbs, known as CRB1, that is mutated in the eye disorders, retinitis
      pigmentosa and Leber congenital amaurosis. Our work has demonstrated that human
      CRB1 can form a complex with mammalian orthologues of Stardust and Discs Lost,
      known as protein associated with Lin-7 (Pals1) and Pals1 associated tight
      junction (PATJ), respectively. In the current report we have cloned a full length
      cDNA for a human paralogue of CRB1 called Crumbs3 (CRB3). In contrast to
      Drosophila Crumbs and CRB1, CRB3 has a very short extracellular domain but like
      these proteins it has a conserved intracellular domain that allows it to complex
      with Pals1 and PATJ. Mouse and human CRB3 have identical intracellular domains
      but divergent extracellular domains except for a conserved N-glycosylation site.
      CRB3 is localized to the apical surface and tight junctions but the conserved N
      linked glycosylation site does not appear to be necessary for CRB3 apical
      targeting. CRB3 is a specialized isoform of the Crumbs protein family that is
      expressed in epithelia and can tie the apical membrane to the tight junction.

PMID- 12527194
TI  - Cloning and analysis of a FoxO transcription factor from Xiphophorus.
AB  - Melanoma development in the fish Xiphophorus is determined, at least in part, by
      overexpression and activation of the Xmrk-2 oncogene, which triggers a variety of
      signal transduction pathways resulting in altered cell cycle control. We have
      begun analysing transcription factors which may link Xmrk-2 with regulation of
      cell proliferation or apoptosis. Towards this end, we have cloned an FKHR (FoxO
      sub-family) homolog from Xiphophorus maculatus. The isolated clone is a 2.7 kb
      cDNA encoding a predicted protein of 664 amino acids. The gene, which we have
      named FoxO5, maps to Xiphophorus Linkage Group XV. The protein product can be
      categorized within a branch of the FOXO sub-class, which includes: Danio rerio
      zFKHR (foxo5), Homo sapiens FKHR-L1 (FoxO3a) and Mus musculus FKHR2 (Foxo3).
      Notably, the Forkhead DNA binding domain, three Akt consensus phosphorylation
      sites and a carboxy-terminal minimal activation domain are each highly conserved.
      A mutated FoxO5 protein with disrupted Akt phosphorylation sites inhibits
      proliferation, but the wild-type protein fails to do so, when exogenously
      expressed in Xiphophorus cells derived from a melanoma. The same mutated protein
      predominantly localizes to the nucleus, yet the wild-type protein seldom does.
      Further characterization of Xiphophorus FoxO5 will contribute to understanding
      the molecular basis of carcinogenesis in these species.

PMID- 12527195
TI  - Two new avian mitochondrial genomes (penguin and goose) and a summary of bird and
      reptile mitogenomic features.
AB  - We report complete mitochondrial (mt) genomes for a penguin (little blue,
      Eudyptula minor) and a goose (greater white-fronted, Anser albifrons). A revised
      annotation of avian and reptile mt genomes has been carried out, which improves
      consistency of labeling gene start and stop positions. In conjunction with this,
      a summary of mt gene features is presented and a number of conserved patterns and
      interesting differences identified. The protein-coding genes from the two new
      genomes were analysed together with those from 17 other birds plus outgroup
      (reptile) taxa. The unrooted amino acid tree from 19 avian genomes was locally
      stable with many high bootstrap values using several maximum likelihood methods.
      In particular, Anseriformes (goose and duck) grouped strongly with Galliformes
      (chicken) to form Gallianseres, while the penguin paired firmly with the stork.
      The position where the outgroup joined the avian tree varied with the combination
      of outgroup taxa used. The three best supported positions of the root were
      passerine, but the traditional rooting position between paleognaths and neognaths
      could not be excluded.

PMID- 12527196
TI  - Evidence implicating Ku antigen as a structural factor in RNA polymerase II
      mediated transcription.
AB  - Ku antigen is an abundant nuclear protein with multiple functions that depend
      mainly on Ku's prolific and highly verstatile interactions with DNA. We have
      shown previously that the direct binding of Ku in vitro to negative regulatory
      element 1 (NRE1), a transcriptional regulatory element in the long terminal
      repeat of mouse mammary tumour virus, correlates with the regulation of viral
      transcription by Ku. In this study, we have sought to explore the interaction of
      Ku with NRE1 in vivo in yeast one-hybrid experiments. Unexpectedly, we observed
      that human Ku70 carrying a transcriptional activation domain from the yeast Gal4
      protein induced transcription of yeast reporter genes pleiotrophically,
      independent of NRE1, promoter, reporter gene and chromosomal location. Ku80 with
      the same activation domain had no effect on transcription when expressed alone,
      but reconstituted activation when co-expressed with native human Ku70. The
      requirements for transcriptional activation by Ku-Gal4 activation domain proteins
      correlated with previous descriptions of the requirements for DNA sequence
      independent DNA binding by Ku, but were distinct from determinants for DNA-end
      binding by a truncated Ku heterodimer determined recently by crystallography.
      These results suggest a preferential targeting of Ku to transcriptionally active
      chromatin that indicate a possible function for Ku within the RNA polymerase II
      holoenzyme.

PMID- 12527197
TI  - Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse
      development.
AB  - Expression and function of homeobox genes (Hox genes) in development have been
      subject to extensive study in a variety of organisms including mammals, however
      practically nothing is known regarding the methylation patterns of these genes.
      Here we describe the methylation patterns of HoxA5 and HoxB5 in various tissues
      of fetal and adult mice and their relevance to expression. Both genes exhibit
      tissue specific methylation patterns that are established postnatally. This
      methylation appears to play a role in stabilizing the newly acquired silent state
      of the genes. In contrast to the postimplantation wave of de novo methylation
      that takes place across the mammalian genome, the methylation of the Hox genes
      represents a different time window for de novo methylation which might be
      characteristic of developmental genes. In the case of HoxA5 this postnatal de
      novo methylation can cover a domain of at least 25 kb that includes several genes
      of the HoxA cluster and the CpG islands within. Our observations suggest that the
      establishment of tissue specific methylation patterns of HoxA5 and HoxB5 and the
      relationship between these methylation patterns and activity are different from
      what had been known for non-developmental genes. This may reflect the specialized
      functions played by Hox genes in development.

PMID- 12527198
TI  - Gene structure and alternative splicing of glycogen synthase kinase 3 beta (GSK
      3beta) in neural and non-neural tissues.
AB  - Glycogen synthase kinase 3 beta (GSK-3beta) is a multifaceted serine-threonine
      kinase that is of interest both because of its role in the canonical Wnt
      signaling pathway, which is involved in mammalian brain regionalization, and its
      role in phosphorylating the microtubule-associated protein Tau. Because of the
      potential association of GSK-3beta with human developmental and neurodegenerative
      conditions, we determined its exon/intron boundaries by a combination of
      sequencing, polymerase chain reaction (PCR) and database mining. Study of GSK
      3beta expression using reverse transcription-PCR, Western blotting and Northern
      blotting showed alternative splicing in nervous and non-nervous system tissues.
      Both at the protein and mRNA level we were able to identify two isoforms, one
      full length form containing exon 10 and one without exon 10. At the mRNA level we
      identified an additional exon that is sometimes seen between exons 8 and 9.
      Furthermore, rather than the reported 2-3 kb mRNA predominant in non-neural
      tissues, we identified the major brain isoforms of GSK-3beta as two high
      molecular weight RNAs (8.4 and 7.7 kb).

PMID- 12527199
TI  - Genomic structure and analysis of transcriptional regulation of the mouse zinc
      fingers and homeoboxes 1 (ZHX1) gene.
AB  - The mouse zinc-fingers and homeoboxes 1 (ZHX1) gene was cloned and its
      transcriptional regulatory mechanism analysed. The mouse ZHX1 gene spans
      approximately 29 kb and consists of five exons. Exons 1-3 contain the nucleotide
      sequence of the 5'-noncoding region of mouse ZHX1 cDNA, exon 4 contains a part of
      the 5'-noncoding region, an entire coding sequence, and a part of the 3'
      noncoding sequence, and exon 5 contains the resulting 3'-noncoding sequence. The
      ZHX1 gene exists as one copy in the haploid mouse genome. Two species of ZHX1
      mRNA with or without the nucleotide sequence of the third exon are produced by an
      alternative splicing. To investigate the regulatory elements involved in the
      transcription of the ZHX1 gene, transient DNA transfection experiments with
      ZHX1/firefly luciferase reporter genes were performed using a lipofection method.
      Functional analyses of a series of 5'- and 3'-deletion constructs of the reporter
      genes revealed that the nucleotide sequence between -59 and +50 is required for
      full promoter activity in mouse embryonal carcinoma F9 cells. Two positive
      regulatory cis-acting elements in the region were identified. These elements,
      designated as Box A and Box B, are located between nucleotides -47 and -42 and
      +22 and +27, respectively, and synergistically stimulate transcription of the
      mouse ZHX1 gene. Electrophoretic mobility shift assays with specific competitors
      and antibodies show that PEA3 and Yin and Yang 1 (YY1) bind to Box A and Box B,
      respectively. Thus, we conclude that PEA3 and YY1 synergistically stimulate the
      transcription of the ZHX1 gene.

PMID- 12527200
TI  - The invertebrate ancestry of endocannabinoid signalling: an orthologue of
      vertebrate cannabinoid receptors in the urochordate Ciona intestinalis.
AB  - The G-protein coupled cannabinoid receptors CB(1) and CB(2) are activated by
      Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of cannabis, and
      mediate physiological effects of endogenous cannabinoids ('endocannabinoids').
      CB(1) genes have been identified in mammals, birds, amphibians and fish, whilst
      CB(2) genes have been identified in mammals and in the puffer fish Fugu rubripes.
      Therefore, both CB(1) and CB(2) receptors probably occur throughout the
      vertebrates. However, cannabinoid receptor genes have yet to be identified in any
      invertebrate species and the evolutionary origin of cannabinoid receptors is
      unknown. Here we report the identification of CiCBR, a G-protein coupled receptor
      in a deuterostomian invertebrate - the urochordate Ciona intestinalis - that is
      orthologous to vertebrate cannabinoid receptors. The CiCBR cDNA encodes a protein
      with a predicted length (423 amino-acids) that is the intermediate of human CB(1)
      (472 amino-acids) and human CB(2) (360-amino-acid) receptors. Interestingly, the
      protein-coding region of the CiCBR gene is interrupted by seven introns, unlike
      in vertebrate cannabinoid receptor genes where the protein-coding region is
      typically intronless. Phylogenetic analysis revealed that CiCBR forms a clade
      with vertebrate cannabinoid receptors but is positioned outside the CB(1) and
      CB(2) clades of a phylogenetic tree, indicating that the common ancestor of CiCBR
      and vertebrate cannabinoid receptors predates a gene (genome) duplication event
      that gave rise to CB(1)- and CB(2)-type receptors in vertebrates. Importantly,
      the discovery of CiCBR and the absence of orthologues of CiCBR in protostomian
      invertebrates such as Drosophila melanogaster and Caenorhabditis elegans indicate
      that the ancestor of vertebrate CB(1) and CB(2) cannabinoid receptors originated
      in a deuterostomian invertebrate.

PMID- 12527201
TI  - Human CRYL1, a novel enzyme-crystallin overexpressed in liver and kidney and
      downregulated in 58% of liver cancer tissues from 60 Chinese patients, and four
      new homologs from other mammalians.
AB  - Lambda-crystallin is a composition of lens in rabbit and hare. It contains the
      putative NAD- or FAD-binding domain, which is named as HCDH domain in 3
      hydroxyacyl-CoA dehydrogenase. In our attempt to search for genes differentially
      expressed between liver cancer tissues and normal tissues, human CRYL1
      (crystallin, lambda 1) was identified. It was downregulated in 58% of 60 Chinese
      HCC tissue samples. The putative protein encoded by CRYL1 shares 83% identity
      with rabbit lambda-crystallin and contains two HCDH domains. Interestingly, CRYL1
      mRNA level is remarkably high in liver and kidney, while it is extremely low in
      peripheral blood leukocyte and thymus. The CRYL1mRNA levels in liver and kidney
      are about 1.6 and 1.2 times the total amount of that in other 14 tissues,
      respectively. Both the special expression pattern and the putative HCDH structure
      of CRYL1 suggested that the protein may be of the similar function of 3
      hydroxyacyl-CoA dehydrogenase. To further understand the lambda-crystallin
      protein family, we cloned four novel mammalian homologs from mouse, rat, bovine
      and pig. The unrooted phylogenetic tree of this protein family including human
      and other 26 species was drawn to analyse their evolutionary relationship. In
      addition, human CRYL1 was mapped to chromosome 13q12.11 and mouse Cryl1 to
      chromosome 14 between marker D14Mit83 and D14Mit260.

PMID- 12527203
TI  - Molecular phylogenetics of the RrmJ/fibrillarin superfamily of ribose 2'-O
      methyltransferases.
AB  - Recent analyses identified a putative catalytic tetrad K-D-K-E common to several
      families of site-specific methyltransferases (MTases) that modify 2'-hydroxyl
      groups of ribose in mRNA, rRNA and tRNA (designated the RrmJ class after one of
      the structurally characterized members; 1eiz in Protein Data Bank) [Genome Biol.
      2(9) (2001) 38]. Subsequently, three residues of the tetrad (K-D-K) were shown to
      be essential for catalysis in RrmJ [J. Biol. Chem. 277 (2002) 41978]. Here, we
      report identification of a similar conserved tetrad (K-D-K-H) in the family of
      snoRNA-guided ribose 2'-O-MTases related to fibrillarin (represented by the
      Mj0697 protein structure; 1fbn in PDB). The corresponding functional groups of
      putative catalytic tetrads of RrmJ and Mj0697 may be superimposed in space.
      However, one of the invariant residues (K(164) in RrmJ and K(179) in Mj0697) is
      observed in two distinct locations in the primary sequence, suggesting an
      interesting case of 'migration' of the conserved side chain within the framework
      of the active site. RrmJ and Mj0697 sequences were used as starting points to
      carry out comprehensive sequence database searches, resulting in identification
      of a similar conserved tetrad (and hence, prediction of a ribose 2'-O
      specificity) in several families of putative MTases, including TlyA hemolysins,
      novel proteins from Trypanosoma, and large multidomain proteins from
      Flaviviriruses, Nidoviruses, and Alphaviruses. The results of our analysis of
      phylogenetic relationships in the RrmJ/fibrillarin superfamily provide insight
      into the evolution of site-specific and snoRNA-guided ribose 2'-O-MTases from a
      common ancestor.

PMID- 12527202
TI  - Expression of the human Hand1 gene in trophoblastic cells is transcriptionally
      regulated by activating and repressing specificity protein (Sp)-elements.
AB  - The tissue-specific basic helix-loop-helix protein Hand1 is essential for the
      formation of trophoblast giant cells of the murine placenta. In humans, Hand1 is
      detectable in trophoblastic tumour cells suggesting an equivalent role in
      trophoblast differentiation. To understand its mode of expression we have cloned
      and characterized the human Hand1 gene promoter. Primer extension analyses
      suggest that transcription initiates 19 nucleotides downstream of the TATA
      element of the proximal 5' flanking region. Expression of luciferase reporter
      constructs harboring deletions of the 9.5 kb Hand1 5' flanking sequence defines a
      promoter region within 274 bp upstream of the transcriptional start site.
      Compared to a reporter bearing only the TATA box, the proximal promoter activates
      transcription up to 30-fold. However, transcriptional activity of the region was
      observed in both Hand1-expressing and non-expressing cell lines. Sequencing,
      DNAseI footprint analyses and electrophoretic mobility shift assays reveal the
      presence of four GC-rich sequences, which show different affinities to the
      endogenous specificity proteins (Sp), and a CCAAT box. In vitro, the Sp-elements
      mainly interact with Sp1 and Sp3 while the CCAAT element is recognized by the
      alpha CAAT binding factor protein. Mutant luciferase reporters bearing single
      active or inactive recognition sites demonstrate that two of the four Sp-binding
      sites (I and IV) contribute little to the overall transcription rate. The two
      other Sp-cognate sequences, II and III, downregulate and activate reporter
      expression 2.3- and 2.6-fold, respectively. Co-transfections of Sp1/Sp3
      expression vectors and mutated reporter constructs in Sp-deficient SL2 cells
      indicate that the Sp-binding site II and III indeed function as repressing and
      activating enhancer sequences. In summary, the data suggest that constitutive
      expression of the Hand1 gene in cultured cells is regulated by a complex
      interplay of Sp-proteins interacting with activator and repressor elements.

PMID- 12527204
TI  - Genomic structure of the human BCCIP gene and its expression in cancer.
AB  - Human BCCIPalpha (Tok-1alpha) is a BRCA2 and CDKN1A (Cip1, p21) interacting
      protein. Our previous studies have showed that overexpression of BCCIPalpha
      inhibits the growth of certain tumor cells [Oncogene 20 (2001) 336]. In this
      study, we report the genomic structure of the human BCCIP gene, which contains
      nine exons. Alternative splicing of the 3'-terminal exons produces two isoforms
      of BCCIP transcripts, BCCIPalpha and BCCIPbeta. The BCCIP gene is flanked by two
      genes that are transcribed in the opposite orientation of the BCCIP gene. It lies
      head-to-head and shares a bi-directional promoter with the uroporphyrinogen III
      synthase (UROS) gene. The last three exons of BCCIP gene overlap the 3'-terminal
      seven exons of a DEAD/H helicase-like gene (DDX32). Using a matched normal/tumor
      cDNA array, we identified a reduced expression of BCCIP in kidney tumor,
      suggesting a role of BCCIP in cancer etiology.

PMID- 12527205
TI  - Diversity of mouse proton-translocating ATPase: presence of multiple isoforms of
      the C, d and G subunits.
AB  - Vacuolar-type proton-translocating ATPases (V-ATPases), multimeric proton pumps,
      are involved in a wide variety of physiological processes. For their diverse
      functions, V-ATPases utilize a specific subunit isoform(s). Here, we reported the
      molecular cloning and characterization of three novel subunit isoforms, C2, d2
      and G3, of mouse V-ATPase. These isoforms were expressed in a tissue-specific
      manner, in contrast to the ubiquitously expressed C1, d1 and G1 isoforms. C2 was
      expressed predominantly in lung and kidney, and d2 and G3 specifically in kidney.
      We introduced these isoforms into yeasts lacking the corresponding genes.
      Although the G3 and d2 did not rescue the vmaDelta phenotype, d1 and the two C
      isoforms functionally complemented the Deltavma6 and Deltavma5, respectively,
      indicating that they are bona fide subunits of V-ATPase.

PMID- 12527206
TI  - Identification of regulatory regions within the KAI1 promoter: a role for binding
      of AP1, AP2 and p53.
AB  - The mechanism underlying loss of KAI1 gene expression in invasive and metastatic
      tumour cells is unknown. A possible scenario could involve altered expression or
      function of protein factors normally involved in regulating KAI1 transcription.
      To explore this possibility, we have initiated a study to characterise regulatory
      elements of the KAI1 promoter, using as a model, two bladder cancer cell lines
      (BL13 and HT1376) expressing high levels of endogenous KAI1 messenger RNA (mRNA).
      Transfection experiments using reporter plasmids with progressive KAI1 promoter
      deletions, identified a 76 bp region upstream of the transcription initiation
      site which contained putative binding motifs for AP2, p53 and AP1, as essential
      for reporter activity. DNA-binding studies using nuclear extracts from both cell
      lines, showed that AP1 and AP2 formed specific complexes with oligonucleotides
      containing KAI1 promoter motifs. Mutation of either motif abrogated reporter
      activity and abolished specific complex formation. In BL13 cells (endogenous
      wildtype p53), but not in HT1376 cells (endogenous mutant p53), mutation of the
      p53-binding motif also abrogated reporter activity and abolished specific complex
      formation in gel shift assays. These data suggested that a combination of AP2,
      p53 and AP1 binding to specific motifs within the KAI1 promoter might be required
      for high level promoter activity and that loss of expression or function of these
      factors might contribute to loss of KAI1 expression in invasive tumours and
      tumour cell lines. To explore this possibility, we examined levels of these
      proteins in nuclear extracts of BL13 and HT1376, as well as three bladder cancer
      cell lines which expressed little or no KAI1 mRNA. Our data suggested that a loss
      of KAI1 mRNA was not simply due to absence of AP2, AP1 or p53 expression.

PMID- 12527207
TI  - Yeast is selectively hypersensitised to heat shock protein 90 (Hsp90)-targetting
      drugs with heterologous expression of the human Hsp90beta, a property that can be
      exploited in screens for new Hsp90 chaperone inhibitors.
AB  - Heat shock protein 90 (Hsp90) is essential for activation of many of the most
      important regulatory proteins of eukaryotic cells. It is an extremely conserved
      protein, such that heterologous expressions of either human Hsp90beta or
      Caenorhabditis elegans Hsp90 will provide the essential Hsp90 function in yeast.
      The ability of these metazoan Hsp90s to provide this Hsp90 function to yeast
      cells requires Sti, a Hsp90 system cochaperone. Yeast that is expressing human
      Hsp90beta in place of the normal native yeast Hsp90 is selectively
      hypersensitised to Hsp90 inhibitor drugs. Hsp90 drugs are promising anticancer
      agents, their administration simultaneously destabilizing a number of the
      proteins critical to multistep carcinogenesis. Though one of these drugs (17
      allylaminogeldanamycin, 17-AAG) is now progressing to Phase 2 clinical trials,
      there is a pressing need to identify selective Hsp90 inhibitors that are more
      soluble than 17-AAG. High-throughput screening for chemical agents that exert
      greater inhibitory effects against yeast expressing the human Hsp90beta relative
      to yeast expressing its native Hsp90 should therefore facilitate the search for
      new Hsp90 inhibitors.

PMID- 12527208
TI  - Chalcone isomerase gene from rice (Oryza sativa) and barley (Hordeum vulgare):
      physical, genetic and mutation mapping.
AB  - The barley and rice chalcone flavonone isomerase (Cfi) genes were isolated and
      identified by homology to the maize Cfi gene. Structure analysis indicated high
      similarity except that the barley gene lacked intron 3. The maize Cfi gene has
      been mapped to three loci, but only a single locus was detected in barley and
      rice. This explains the lack of observed mutants in maize while a single locus
      anthocyanin-less 30 (ant30), with four alleles ant30-245, ant30-310, ant30-272
      and ant30-287 has been described in barley. Based on biochemical analysis it has
      been suggested that these mutants are in the Cfi gene resulting in absence of
      anthocyanin. In order to provide molecular evidence for or against this
      hypothesis we sequenced the four ant30 alleles and compared them to their
      respective wild-type alleles. The three sodium azide induced mutants ant30-245,
      ant30-272 and ant30-287 showed single base changes resulting in two non-sense and
      one mis-sense mutations affecting the protein function. The 1-nitroso-5,6
      dihydrouracil induced mutant ant30-310 had one base substitution and a 25 bp
      deletion. These observations are in accordance with the conclusion that the ant30
      phenotype is caused by mutations in the Cfi gene. The nature of the mutants
      induced is in line with the proposed mechanism of action for the mutagens used.

PMID- 12527209
TI  - Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling.
AB  - Dickkopf1 (Dkk1) is a secreted antagonist of the Wnt/beta-catenin signaling
      pathway that acts by direct binding to and inhibiting the Wnt co-receptor LRP6.
      The related Dkk2, however, can function either as LRP6 agonist or antagonist,
      depending on the cellular context, suggesting that its activity is modulated by
      unknown co-factors. We have recently identified the transmembrane proteins
      Kremen1 and -2 as additional Dkk receptors, which bind to both Dkk1 and Dkk2 with
      high affinity. Here we show that Kremen2 (Krm2) regulates Dkk2 activity during
      Wnt signaling. In human 293 fibroblasts transfected dkk2 activates LRP6
      signaling. However, co-transfection of krm2 blocks the ability of Dkk2 to
      activate LRP6 and enhances inhibition of Wnt/Frizzled signaling. Krm2 also co
      operates with Dkk4 to inhibit Wnt signaling, but not with Dkk3, which has no
      effect on Wnt signaling. Likewise, in Xenopus embryos, Dkk2 and Krm2 co-operate
      in Wnt inhibition leading to anteriorized embryos. Finally, we show that
      interaction with Krm2 is mediated by the second cysteine-rich domain of Dkks.
      These results suggest that Krm2 can function as a switch that turns Dkk2 from an
      activator into an inhibitor of Wnt/lRP6 signaling.

PMID- 12527210
TI  - The Serratia marcescens bioH gene encodes an esterase.
AB  - The 3.9 kb chromosomal DNA was cloned from Serratia marcescens Sr41, which
      confers on Escherichia coli cells a phenotype of clear halo formation on
      tributyrin agar plates. Three complete open reading frames (ORFs) were identified
      in the inserted DNA, and one ORF was demonstrated to encode a 28 kDa protein of
      255 amino acids related to esterase activity. Interestingly, the ORF was 70%
      identical to a product of the E. coli bioH gene, which lies at a locus separated
      from the bioABFCD operon and acts in the early steps of the biotin synthetic
      pathway before pimeloyl-CoA synthesis. This gene complemented a bioH-deficient
      mutation of E. coli. From the sequence analysis, BioH is presumed to be a serine
      hydrolase, which belongs to the alpha/beta hydrolase-fold family comprising a
      wide variety of hydrolases including esterases. A catalytic triad composed of a
      nucleophilic residue (Ser80), an acidic residue (Asp206), and histidine (His234)
      was conserved in BioH, and the nucleophilic residue Ser, a catalytic center, was
      situated in the consensus sequence of G-X-S-X-G-G, a nucleophile elbow. Although
      the enzymatic function of BioH is not yet elucidated, the bioH gene products from
      S. marcescens and E. coli show esterase activity, which may imply the hydrolysis
      of a precursor leading to pimeloyl-CoA ester. The esterase activity of BioH and
      its CoA binding activity recently reported agree with a current hypothesis of
      pimeloyl-CoA ester synthesis from CoA and acylester derivatives including an acyl
      carrier protein.

PMID- 12527211
TI  - Comparative study of HP-27 gene promoter activities between the chipmunk and tree
      squirrel.
AB  - The chipmunk hibernation-specific protein HP-27 is a component of the 140-kDa
      complex that decreases in the blood during hibernation. Although the HP-27 gene
      is detected in both the chipmunk, a hibernating species of the squirrel family,
      and the tree squirrel, a nonhibernating species, it is expressed only in the
      chipmunk, in a liver-specific manner. To understand the difference in HP-27 gene
      expression between the chipmunk and tree squirrel, we isolated chipmunk and tree
      squirrel HP-27 genomic clones, and compared their promoter activities. Transient
      transfection studies in HepG2 cells revealed that the 170 bp 5'-flanking sequence
      of the chipmunk HP-27 gene was sufficient for liver-specific promoter activity
      and that deletion of the sequence from -170 to -140 reduced the promoter activity
      by 90%. Although the corresponding 170 bp 5'-flanking sequence of the tree
      squirrel HP-27 gene had 89% nucleotide sequence homology to that of the chipmunk,
      it showed almost no promoter activity in HepG2 cells. In a gel retardation assay
      using HepG2 or chipmunk liver nuclear extracts, the 5'-flanking sequence of the
      chipmunk HP-27 gene from -170 to -140 showed a shifted band, but the
      corresponding tree squirrel sequence did not. Taken together, these data indicate
      that a transcription factor that binds to this 5'-flanking sequence of the
      chipmunk HP-27 gene plays an important role in HP-27 gene expression, and the
      failure of this factor to bind in the case of the tree squirrel HP-27 gene could
      be responsible for this animal's lack of HP-27 gene expression.

PMID- 12527213
TI  - Recognition of pathogen-associated molecular patterns by TLR family.
AB  - Toll-like receptors (TLRs) are type I transmembrane proteins involved in innate
      immunity by recognizing microbial conserved structures. Recent studies have shown
      that TLR3 recognizes dsRNA, a viral product, whereas TLR9 recognizes unmethylated
      CpG motifs frequently found in the genome of bacteria and viruses, but not
      vertebrates. TLR7 recognizes small synthetic immune modifiers including
      imiquimod, R-848, loxoribine, and bropirimine, all of which are already applied
      or promising for clinical use against viral infections and cancers. Plasmacytoid
      dendritic cells express TLR7 and TLR9, and respond to TLR7 and TLR9 ligands by
      producing a large amount of interferon (IFN-alpha). These results indicate that
      TLR3, TLR7 and TLR9 may play an important role in detecting and combating viral
      infections.

PMID- 12527214
TI  - The role of dendritic cells in the immune response to Salmonella.
AB  - Dendritic cells (DC) are an important link between the innate and adaptive immune
      response and are key antigen presenting cells in triggering specific immunity.
      This review summarizes the role of DC and the DC subsets during infection with
      the facultative intracellular bacterium Salmonella. The capacity of DC to
      stimulate Salmonella-specific T cells by direct and indirect presentation of
      Salmonella antigens as well as the cytokine production capacity of DC upon
      Salmonella encounter are discussed. In addition, changes in the number,
      localization and cytokine production by splenic DC subsets during infection are
      reviewed. Studying the function of DC during Salmonella infection provides
      insight into the capacity of this phagocytic antigen presenting cell to initiate
      and modulate an immune response during bacterial infection.

PMID- 12527215
TI  - Lymphocyte traffic control by chemokines: follicular B helper T cells.
AB  - Follicular B helper T (T(FH)) cells make up a CD4(+) memory T cell subset with
      unique migration properties, defined by the expression of the chemokine receptor
      CXCR5 and responsiveness to the CXCR5-selective chemokine BCA-1, which is
      produced in B cell follicles. The generation of T(FH) cells is closely associated
      with initiation of adaptive immunity. Here, we discuss the relationship of T(FH)
      cells with those T cells characterized by an inherent secondary lymphoid tissue
      homing program. Special emphasis is placed on the potential involvement of T(FH)
      cells in the humoral immune response within B cell follicles, as well as the
      differentiation potential of these non-polarized cells.

PMID- 12527216
TI  - HIV-1 entry inhibitors: new targets, novel therapies.

PMID- 12527217
TI  - Regulation of T cell migration during viral infection: role of adhesion molecules
      and chemokines.
AB  - T cell mediated immunity and in particular CD8+ T cells are pivotal for the
      control of most viral infections. T cells exclusively exert their antiviral
      effect through close cellular interaction with relevant virus-infected target
      cells in vivo. It is therefore imperative that efficient mechanisms exist, which
      will rapidly direct newly generated effector T cells to sites of viral
      replication. In the present report we have reviewed our present knowledge
      concerning the molecular interactions, which are important in targeting of
      effector CD8+ T cells to sites of viral infection.

PMID- 12527218
TI  - The role of innate cytokines in inflammatory response.
AB  - Mediators produced by innate immune response cells such as macrophages can
      profoundly influence adaptive immunity. Recent studies have shown that IL-15 and
      IL-18 play an influential role in inflammatory response. Here I present recent
      data mainly from our own laboratories illustrating the importance of IL-15 and IL
      18 in the induction and perpetuation of chronic inflammation during experimental
      and clinical rheumatoid synovitis. These findings suggest that antagonists to
      these cytokines may have a potential therapeutic role against organ-specific
      autoimmune diseases.

PMID- 12527219
TI  - In vitro generation of IL-10-producing regulatory CD4+ T cells is induced by
      immunosuppressive drugs and inhibited by Th1- and Th2-inducing cytokines.

PMID- 12527220
TI  - CD25+ regulatory T cells and tumor immunity.
AB  - Tumor cells express a range of antigens including self-antigens (those whose
      expression is shared by normal host tissue) and non-self antigens (such as those
      that arise as a result of mutations in normal cellular genes or in the case of
      some tumors, viral antigens). Immune responses to both types of antigen have been
      identified in human patients with cancer and in murine tumor models. In both
      cases, these responses are typically weak and generally fail to result in tumor
      rejection. Accumulating evidence indicates that a population of T cells, namely
      CD25(+) regulatory cells, is at least partly responsible for the poor
      immunogenicity of tumor cells. This evidence is discussed in the context of a
      murine model of melanoma.

PMID- 12527221
TI  - Cytokines and T cell homeostasis.
AB  - In recent years it has become apparent that the long-term survival of T cells
      requires continuous contact with external stimuli. At least two types of stimuli,
      namely self antigens and cytokines, are involved in maintaining T cell viability.
      As discussed here, the factors controlling T cell survival and turnover in vivo
      differ considerably from one T cell subset to another.

PMID- 12527222
TI  - Dendritic cells as a tool to combat infectious diseases.
AB  - Dendritic cells (DCs) form a network of potent antigen-presenting cells that
      initiate and amplify immune responses. The detection and capture of
      microorganisms by DCs trigger stimulus-specific maturation programs that enable
      DCs to convey pathogen-associated signals to the adaptive branch of the immune
      system. The appropriate activation of DCs is critical for their ability to direct
      the development of either a Th1 or a Th2 response, thereby determining the
      outcome of microbial infections. Advances in the understanding of DC interactions
      with microbes provide new concepts for immune interventions. In different models
      of infectious disease, it has been demonstrated that DCs can serve as vaccine
      carriers, mediating protection against various types of pathogens. The studies of
      the requirements of ex vivo manipulations of DCs may lead to the design of
      vaccines that induce protective immunity to infections by appropriate targeting
      of DCs in vivo.

PMID- 12527223
TI  - NKT cell subsets in infection and inflammation.
AB  - We recently identified two stably expressed cell surface markers, IL-18R and
      ST2L, which are selectively expressed on T1/NK1 and T2/NK2 cells, respectively.
      Here we use these molecules in direct ex vivo analysis of PBMCs from patients
      with AIDS, psoriasis (PS) atherosclerosis and to show the importance of these
      markers as determinants of the functional dichotomy of lymphocyte subsets, in
      particular NKT. In a cohort of 22 HIV patients made up of a mixture of long term
      non-progressors, seroconvertors, progressors and asymptomatics, we found a clear
      NKT1 to NKT2 shift (P=0.001) in the HIV-infected individuals. We also show a
      predominance of NKT2 cells over NKT1 cells in the PBMCs of patients with mild to
      moderate PS (N=13, P=0.005) but not in atopic dermatitis or healthy controls.
      However, in patients (N=6) requiring surgery for aneurysm, a predominance of Type
      1 (IL-18R(+)) NKT lymphocytes over NKT2 was detected among infiltrating
      lymphocytes isolated from atherosclerotic plaques. Our data therefore demonstrate
      that ST2L and IL-18R could serve as important determinants of the immune status
      of human diseases.

PMID- 12527224
TI  - Viral escape and T cell exhaustion in hepatitis C virus infection analysed using
      Class I peptide tetramers.
AB  - Hepatitis C virus (HCV) has infected over 170 million people world wide, and in
      the majority sets up a chronic infection associated with hepatic inflammation.
      How it evades host immunity, particularly CD8+ T cells (CTL) is unclear, but two
      major factors are likely to operate, viral escape mutation and T cell exhaustion.
      We have investigated the role of CTL in control of infection during acute disease
      using Class I peptide tetramers. Although the immune response is quite diverse
      and numerous epitopes can be targeted, we observe that, especially during acute
      disease, one epitope (NS3 1073-81) is commonly recognised in HLA-A2 positive
      individuals. However, the levels of response to this epitope (and others) are
      very much lower if persistence is established. We examined in detail whether the
      cause of this low level of reactivity is due to mutation within the epitope. We
      find that, in fact this epitope is highly conserved during chronic infection, at
      a clonal level, between individuals, and over time. Thus, although variation
      within the epitope does occur, lack of reactivity in peripheral blood against
      this epitope in chronic disease, and loss of control of virus cannot be explained
      entirely by viral escape. Escape through mutation probably does play an important
      role in persistence of HCV, but we also discuss other mechanisms which lead to
      attenuation of T cell responses which may be important in determining the
      outcome.

PMID- 12527225
TI  - Macrophages in chronic type 2 inflammation have a novel phenotype characterized
      by the abundant expression of Ym1 and Fizz1 that can be partly replicated in
      vitro.
AB  - Using a murine model of nematode infection, we have discovered macrophages that
      display a novel phenotype that may be characteristic of macrophages in chronic
      type 2 inflammation. These nematode-elicited macrophages (NeMphi) are
      characterized by two unique features: the ability to actively suppress
      proliferation of a broad range of cell types and the high level expression of two
      novel macrophage genes, Ym1 and Fizz1. NeMphi also show some similarities with in
      vitro-derived 'alternatively activated macrophages' such as the downregulation of
      inflammatory cytokines. We therefore investigated how much of the phenotype
      discovered in vivo could be replicated by activation with Th2 cytokines in vitro.
      Fizz1 and Ym1 were upregulated by IL-4 and IL-13 in vitro but at a considerably
      lower level than in NeMphi. In vitro treatment with IL-4 could also partly
      replicate the ability of NeMphi to block cellular proliferation. As well as the
      quantitative differences in gene expression and suppressive phenotype, we also
      observed phenotypic differences in the cell morphology between macrophages
      activated in vivo and in vitro. Although this study illustrated that macrophages
      activated in chronic inflammation have distinct features that cannot be readily
      reproduced in vitro it also demonstrated that some features of the complex NeMphi
      phenotype can be replicated by treatment of cultured macrophages with Th2
      cytokines. In future, we hope to use in vitro analysis to help define the
      pathways that lead to this distinctive in vivo macrophage phenotype.

PMID- 12527226
TI  - The interplay between Salmonella typhimurium and its macrophage host--what can it
      teach us about innate immunity?
AB  - Salmonella enterica sv. Typhimurium (S. typhimurium) is a genetically tractable,
      facultative intracellular pathogen, whose capacity to cause systemic disease in
      mice depends upon its ability to survive and replicate within macrophages. The
      identification of Salmonella mutants that lack this activity, has provided a tool
      with which to dissect the mechanisms used by Salmonella to establish a permissive
      niche, and identify host activities which it must overcome in order to achieve
      this. Salmonella actively maintains itself within an intracellular vacuole,
      thereby shielding itself from an antibacterial activity of host macrophage
      cytosol. Salmonella controls the maturation of its vacuole, segregating itself
      from the macrophage degradative pathway. Like several other pathogens, Salmonella
      reduces the effectiveness of bacteriocidal and bacteriostatic free radicals
      generated by macrophages, by synthesising enzymes and products that counteract
      them. Recent evidence indicates that Salmonella also avoids free radical
      dependent macrophage antimicrobial mechanisms by more novel means. Here, we
      review recent studies of the interplay between pathogen and host, with particular
      emphasis on those areas that suggest new facets to the cell biology of
      macrophages, and their innate immune functions.

PMID- 12527227
TI  - The role of iron in infections with intracellular bacteria.
AB  - The requirement for iron as a critical component for cellular processes has long
      been appreciated. During infection with intracellular bacteria, iron is required
      by both the host cell and the pathogen that inhabits the host cell. Macrophages
      require iron as a cofactor for the execution of important antimicrobial effector
      mechanisms, including the NADPH dependent oxidative burst and the production of
      nitrogen radicals catalysed by the inducible nitric oxide synthase. On the other
      side of the equation, intracellular bacteria such as Salmonella typhimurium and
      Mycobacterium tuberculosis have an obligate requirement for iron to support their
      growth and survival inside cells. This brief report summarises the background to
      our work on iron modulation in infections with these two organisms and highlights
      key observations on how modulation of host iron status disturbs the equilibrium
      between host and pathogen and can determine the outcome of infection.

PMID- 12527228
TI  - Divalent cation transport and susceptibility to infectious and autoimmune
      disease: continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story.
AB  - Solute carrier family 11 member a1 (Slc11a1), formerly known as
      Nramp1/Ity/Lsh/Bcg, is a proton/divalent cation antiporter that regulates
      susceptibility to infectious and autoimmune disease. Here we review recent
      studies on (1) the role of Slc11a1 in iron metabolism and iron recycling in
      macrophages; (2) the use of mouse breeding and introgression of knockouts onto
      Slc11a1 congenic backgrounds for genes encoding the multiple pleiotropic
      functions associated with Slc11a1; and (3) associations/linkages of SLC11A1 with
      human disease and how these relate to functional promoter region polymorphisms.

PMID- 12527229
TI  - A novel TB vaccine; strategies to combat a complex pathogen.
AB  - Years of intense research aimed at developing a new and improved vaccine against
      tuberculosis (TB) are now moving from the laboratories and into the field. Many
      groups have provided strong evidence for the potential of novel vaccines using a
      variety of different strategies and the most promising are just beginning to
      enter human safety trials. As research has developed over the years, the
      complexity of the TB situation at the global level and its influence on vaccine
      development strategies has become more and more clear. From being mainly focused
      on the development of a vaccine that could be given at birth and provide lifelong
      protection, it is now clear that the current goal may need to be a vaccine to be
      given to a population where the majority is already sensitized either by previous
      infection, exposure to other mycobacteria or by Bacille Calmette-Guerin
      vaccination. With the increasing awareness of the different immune mechanisms
      operating under those circumstances, such a vaccine still represents a
      significant challenge for immunologists and microbiologists working in this
      field.

PMID- 12527230
TI  - Quantitative assessment of antigen-specific CD8+ T cells in the mouse:
      application to vaccine research.
AB  - An effective HIV vaccine will likely need to induce potent and broad-based
      immunity, including CD8+ T cell responses. Hence, a quantitative assay to measure
      such responses in animal models will be important in the evaluation of candidate
      HIV vaccines. We show here that a single immunization with HIV DNA vaccines,
      followed by challenge with recombinant vaccinia virus expressing the relevant HIV
      antigen, allows quantitative assessment of CD8+ T cell responses. These responses
      can be profound (>30% of total CD8+ T cells) and directly reflect the level of
      memory CD8+ T cells at the time of challenge. Therefore, this assay will
      facilitate the selection of promising HIV vaccine candidates for further
      evaluation.

PMID- 12527231
TI  - Activity concentration of caesium-137 in agricultural soils.
AB  - In this study, we measured 137Cs activity concentrations in the soil samples
      taken from agricultural lands in the Buyuk Menderes Basin in Turkey in 1997 and
      1998. The soil samples were collected from 42 sites in this Basin. The activity
      concentration of 137Cs was found to range between 2.81+/-0.17 Bq.kg(-1) and
      20.75+/-0.29 Bq.kg(-1). The effect of organic matter, clay, silt and sand
      contents and pH of the soil on the relative adsorption of the 137Cs on the soil
      surface were also studied.

PMID- 12527232
TI  - Long period study of outdoor radon concentration in Milan and correlation between
      its temporal variations and dispersion properties of atmosphere.
AB  - The results of a survey of outdoor radon concentrations in Milan are reported.
      Measurements were performed hourly over a continuous four year period from
      January 1997 to December 2000. Radon concentration was obtained by two means:
      both direct measurement of radon; and measurement of its decay products. The
      average daily pattern of radon concentration featured a minimum in the late
      afternoon and a maximum in the early hours of the morning. A seasonal pattern
      with higher concentrations in winter than in summer (from around 15 Bq m(-3) in
      winter to around 5 Bq m(-3) in summer) was also observed. Similar average annual
      values of around 10 Bq m(-3) were obtained. The annual effective outdoor radon
      dose was found to be 0.12 mSv. The variation from minimum in the afternoon to
      maximum the following morning was found to be a good indicator of the height of
      the nocturnal mixing layer. The variation between maximum and minimum levels on
      the same day is an index of the maximum height of the mixing layer. Furthermore,
      our long term measurements of radon have permitted us to examine the dispersion
      characteristics of the atmosphere over Milan, and to establish the frequency of
      conditions unfavourable to the dispersion of atmospheric pollutants.

PMID- 12527233
TI  - Soil-to-plant transfer factors for natural radionuclides and stable elements in a
      Mediterranean area.
AB  - The transfer factors (TF) for natural uranium isotopes (238U and 234U), thorium
      isotopes (232Th, 230Th and 228Th), and 226Ra were obtained in plant samples
      (grass-pasture) growing in granitic and alluvial soils around a disused uranium
      mine located in the Extremadura region in the south-west of Spain. Affected and
      non-affected areas of the mine presented large differences in the activity
      concentrations of radionuclides of the uranium series. We also determined
      transfer factors for several stable elements (essential and non-essential). A set
      of statistical tests were applied to validate the data. The results showed that
      the transfer factors for both the natural radionuclides and the stable elements
      are independent of the two substrate types involved and also of the two areas
      considered in the study.

PMID- 12527234
TI  - Bioaccumulation of 137Cs in pelagic food webs in the Norwegian and Barents Seas.
AB  - Knowledge and documentation of the levels of radioactive contamination in fish
      stocks important to Norwegian fisheries is of major importance to Norwegian
      consumers and fish export industry. In the present study, the bioaccumulation of
      caesium-137 ((137)Cs) has been investigated in marine food webs in the Barents
      and Norwegian Seas. The contents of (137)Cs in the different organisms were
      generally low (<1 Bq kg(-1) wet weight), but a marked bioaccumulation was
      apparent: The concentration of (137)Cs was about 10-fold higher in the harbour
      porpoise Phocoena phocoena, representing the upper level of the food web, than in
      the amphipod Themisto sp., representing the lower level of the food web. The
      Concentration Factors (CF=Bq kg(-1) wet weight/Bq l(-1) seawater) increased from
      10+/-3 for a mixed sample of krill and amphipods to 165+/-5 for harbour
      porpoises.

PMID- 12527235
TI  - Groundwater radon measurements in the Mt. Etna area.
AB  - Radon levels were measured in 119 groundwater samples collected throughout the
      active volcanic area of Mt. Etna by means of a portable Lucas-type scintillation
      chamber. The measured activity values range from 1.8 to 52.7 Bq l(-1). About 40%
      of the samples exceed the maximum contaminant level of 11 Bq l(-1) proposed by
      the USEPA in 1991. The highest radon levels are measured in the eastern sector of
      the volcano, which is the seismically most active zone of the volcano. On the
      contrary the south-western sector, which is both seismically active and a site of
      intense magmatic degassing, display lower radon levels. This is probably due to
      the formation of a free gas phase (oversaturation of CO(2)) that strips the radon
      from the water. Comparison of the data gathered at Mt. Etna with those of other
      areas indicates that (222)Rn activity in groundwater is positively correlated
      with both the content of parent elements in the aquifer rocks and the temperature
      of the geothermal systems that interacts with the sampled aquifers.

PMID- 12527236
TI  - A nationwide survey of outdoor radon concentration in Japan.
AB  - Nationwide outdoor radon (222Rn) concentrations in Japan were measured to survey
      the environmental outdoor 222Rn level and to estimate the effective dose to the
      general public from 222Rn and its progeny. The 222Rn concentration was measured
      with a passive-type radon monitor. The 222Rn monitors were installed at about 700
      points throughout Japan from 1997 to 1999. The annual mean 222Rn concentration in
      Japan was estimated from four quarters measurements of 47 prefectures in Japan.
      Nationwide outdoor mean 222Rn concentration was 6.1 Bq m(-3). This was about 40%
      of the indoor 222Rn concentration in Japan. The 222Rn concentration in Japan
      ranged from 3.3 Bq m(-3) in the Okinawa region to 9.8 Bq m(-3) in the Chugoku
      region, reflecting geological characteristics. Seasonal variation of outdoor
      222Rn concentration was also found to be lowest in July to September, and highest
      in October to December. From the results of this 222Rn survey and previous indoor
      222Rn survey program, the effective dose to the general public from 222Rn and its
      progeny was estimated to be 0.45 mSv y(-1).

PMID- 12527237
TI  - Soil availability, plant uptake and soil to plant transfer of 99Tc--a review.
AB  - The fission yield of 99Tc from 239Pu and 235U is similar to that of 137Cs or 90Sr
      and it is therefore an important component of nuclear weapons fall-out, nuclear
      waste and releases from nuclear facilities. There is particular current interest
      in 99Tc transfer from soil to plants for: (a) environmental impact assessments
      for terrestrial nuclear waste repositories, and (b) assessments of the potential
      for phytoextraction of radionuclides from contaminated effluent and soil.
      Vascular plants have a high 99Tc uptake capacity, a strong tendency to transport
      it to shoot material and accumulate it in vegetative rather than reproductive
      structures. The mechanisms that control 99Tc entry to plants have not been
      identified and there has been little discussion of the potential for
      phytoextraction of 99Tc contaminated effluents or soil. Here we review soil
      availability, plant uptake mechanisms and soil to plant transfer of 99Tc in the
      light of recent advances in soil science, plant molecular biology and
      phytoextraction technologies. We conclude that 99Tc might not be highly available
      in the long term from up to 50% of soils worldwide, and that no single mechanism
      that might be easily targeted by recombinant DNA technologies controls 99Tc
      uptake by plants. Overall, we suggest that Tc might be less available in
      terrestrial ecosystems than is often assumed but that nevertheless the potential
      of phytoextraction as a decontamination strategy is probably greater for 99Tc
      than for any other nuclide of radioecological interest.

PMID- 12527238
TI  - Natural radionuclides in bottled water in Austria.
AB  - Concentration levels of 226Ra, 222Rn and 210Pb were analyzed in domestic bottled
      waters commercially available in Austria. Concentrations up to 0.23 Bq/l, with a
      geometric mean of 0.041 Bq/l were found for 226Ra. Concentrations for 222Rn
      ranged from <0.12-18 Bq/l, the geometric mean being 0.54 Bq/l. Lead-210 was
      analyzed in selected samples, the concentrations ranging from <2 to 34 mBq/l,
      with a geometric mean of 4.7 mBq/l. Ingestion doses resulting from consumption of
      these waters were calculated for the geometric mean and the maximum
      concentrations of the three radionuclides. The effective dose equivalents for
      different age groups of the population due to the intake of 226Ra range from
      0.001 to 0.22 mSv/y and of 210Pb from 0.0003 to 0.05 mSv/y. Ingestion doses from
      222Rn are low compared to those from 226Ra and 210Pb, ranging from 0.0001 to
      0.011 mSv/y for adults and children, respectively. The doses are compared to the
      total ingestion dose from dietary intake of natural radionuclides on an annual
      basis.

PMID- 12527239
TI  - Experimental and Monte Carlo simulation studies of open cylindrical radon
      monitoring device using CR-39 detector.
AB  - There are several methods of measuring radon concentrations but nuclear track
      detector cylindrical dosimeters are widely employed. In this investigation, the
      consequence of effective volumes of the dosimeters on the registration of alpha
      tracks in a CR-39 detector was studied. In a series of experiments an optimum
      radius for a CR-39-based open cylindrical radon dosimeter was found to be about 3
      cm. Monte Carlo simulation techniques have been employed to verify the
      experimental results. In this context, a computer code Monte Carlo simulation
      dosimetry (MOCSID) was developed. Monte Carlo simulation experiments gave the
      optimum radius of the dosimeters as 3.0 cm. The experimental results are in good
      agreement with those obtained by Monte Carlo design calculations. In addition to
      this, plate-out effects of radon progeny were also studied. It was observed that
      the contribution of radon progeny (218Po and 214Po) plated-out on the wall of the
      dosimeters increases with an increase of dosimeter radii and then decrease to 0
      at a radius of about 3 cm if a point detector has been installed at the center of
      the dosimeter base. In the code MOCSID different types of random number
      generators were employed. The results of this research are very useful for
      designing an optimum size of radon dosimeters.

PMID- 12527240
TI  - Rasterstereographic back shape analysis in idiopathic scoliosis after anterior
      correction and fusion.
AB  - OBJECTIVE: To determine the accuracy of rasterstereographic three-dimensional
      back surface analysis and reconstruction of the spine in cases of severe
      idiopathic scoliosis treated by anterior correction and fusion. DESIGN:
      Comparison of digitized radiographic curves and rasterstereographic curves by
      best fit superimposition and calculation of root mean square differences as
      parameters of similarity. BACKGROUND: Rasterstereography has been proven to be
      accurate in scoliosis up to 50 degrees Cobb angle. Since 1989 the device is in
      clinical routine use for non-operatively treated patients and reduces the need
      for otherwise indispensable radiographs significantly. METHODS: Fifty two
      patients with severe idiopathic scoliosis with Cobb angles up to 88 degrees were
      examined rasterstereographically and radiographically. Forty eight pre-operative
      anterior-posterior radiographs and 101 post-operative anterior-posterior
      radiographs were digitized. Radiographic and rasterstereographic curves were
      compared and the root mean square differences were calculated as parameters of
      precision of rasterstereographic reconstruction. RESULTS: Accuracy of
      rasterstereography in idiopathic scoliosis with Cobb angles between 50 degrees
      and 88 degrees is satisfactory. The root mean square difference of the
      radiographic and rasterstereographic curves was 6.4 mm for lateral deviation and
      4.5 degrees for vertebral rotation. After anterior scoliosis surgery the
      precision of the device is good. The root mean square difference for lateral
      deviation was 3.4 mm and 3.2 degrees for rotation. Considering both groups an
      average root mean square of 4.7 mm and 3.7 degrees was calculated. CONCLUSIONS:
      Accuracy in severe scoliosis up to 88 degrees Cobb angle was satisfactory. The
      results of this first evaluation of surgically treated severe scoliosis showed a
      good accuracy after anterior surgery. The system can be used for post-operative
      follow up examinations and may reduce the number of X-rays considerably. In
      contrast to radiography, CT or MRI rasterstereography provides an objective
      quantification and documentation of the post-operative cosmetic improvement of
      the back shape in standing posture. RELEVANCE STATEMENT: Based on the findings of
      this study rasterstereography in future enables both objective quantification of
      cosmetic improvement and significant reduction of X-rays in idiopathic scoliosis
      with Cobb angles higher than 50 degrees before and after anterior surgical
      correction and fusion.

PMID- 12527241
TI  - Surface EMG electrodes do not accurately record from lumbar multifidus muscles.
AB  - OBJECTIVE: This study investigated whether electromyographic signals recorded
      from the skin surface overlying the multifidus muscles could be used to quantify
      their activity. DESIGN: Comparison of electromyography signals recorded from
      electrodes on the back surface and from wire electrodes within four different
      slips of multifidus muscles of three human subjects performing isometric tasks
      that loaded the trunk from three different directions. BACKGROUND: It has been
      suggested that suitably placed surface electrodes can be used to record activity
      in the deep multifidus muscles. METHODS: We tested whether there was a stronger
      correlation and more consistent regression relationship between signals from
      electrodes overlying multifidus and longissimus muscles respectively than between
      signals from within multifidus and from the skin surface electrodes over
      multifidus. RESULTS: The findings provided consistent evidence that the surface
      electrodes placed over multifidus muscles were more sensitive to the adjacent
      longissimus muscles than to the underlying multifidus muscles. The R(2) for
      surface versus intra-muscular comparisons was 0.64, while the average R(2) for
      surface-multifidus versus surface-longissimus comparisons was 0.80. Also, the
      magnitude of the regression coefficients was less variable between different
      tasks for the longissimus versus surface multifidus comparisons. CONCLUSIONS:
      Accurate measurement of multifidus muscle activity requires intra-muscular
      electrodes. RELEVANCE: Electromyography is the accepted technique to document the
      level of muscular activation, but its specificity to particular muscles depends
      on correct electrode placement. For multifidus, intra-muscular electrodes are
      required.

PMID- 12527242
TI  - Neck mobility measurement by means of the 'Flock of Birds' electromagnetic
      tracking system.
AB  - OBJECTIVE: To establish the accuracy and reliability of a six-degrees-of-freedom
      electromagnetic tracking device, the "Flock of Birds", for measuring neck
      rotations and to identify the main sources of error. DESIGN: Ten human subjects
      made the same types of maximal neck rotation, both actively and passively: axial
      rotation in neutral position, from a flexed position and from an extended
      position, flexion/extension and lateral flexion. The same movements were mimicked
      in a 'dummy head' set-up. METHODS: One Flock of Birds receiver was mounted on the
      thorax, one on the head. By means of a third receiver, mounted on a stylus, bony
      landmarks on head and thorax were palpated. These served to define two
      anatomically based local coordinate systems, to which the rotations were
      referred. RESULTS: Measurements were accurate with a maximal measurement error of
      2.5 degrees. No significant difference between active and passive rotation was
      seen. The intra-subject variation was low within the same session, SD between 2
      degrees and 4 degrees. Between sessions the variability was considerable, SD
      between 5 degrees and 16 degrees. CONCLUSION: The Flock of Birds method is
      reliable and sufficiently precise. The variability in measured range of motion
      between sessions is a point of concern in interpreting follow-up studies in
      patients. RELEVANCE: A reduced range of neck motion is a major complaint in
      pathologies of the cervical spine or the shoulder. A method is described in which
      neck rotations are related to well-defined bony landmarks. In combined rotations,
      e.g. flexion combined with axial rotation, the measured range of motion can
      sometimes fluctuate strongly (up to 30 degrees ) between measurements, without
      apparent pathology.

PMID- 12527243
TI  - Semi-rigid vs rigid glass fibre casting: a biomechanical assessment.
AB  - OBJECTIVES: To determine if semi-rigid synthetic casts provide any measurable
      advantages compared to rigid synthetic casts. BACKGROUND: Glass fibre bandages
      are now commonly applied immediately post-injury to provide rigid immobilisation
      of the limb, for both weight bearing and non-weight bearing casts. However,
      composite casts that have inherent flexibility are also available and it is
      claimed they provide some functionality. METHODS: Five members of the orthopaedic
      department each applied a rigid and a semi-rigid below elbow (Colles) and a below
      knee walking cast to a single volunteer subject. Joint immobilisation and
      functional movement was assessed using electrogoniometry and limb support using
      pressure transducers. RESULTS: Semi-rigid Colles casts provided slightly greater
      immobilisation at the wrist while allowing full finger function and greater
      support to the forearm during hand movements. Similarly, semi-rigid below knee
      walking casts produced greater immobilisation at the ankle while allowing more
      forefoot movement and were less of an impediment to walking. CONCLUSIONS: Semi
      rigid casting techniques have measurable advantages compared to rigid synthetic
      casts and represent a further development in the conservative management of
      fractures and soft tissue injuries. RELEVANCE: Semi-rigid casting is a relatively
      new technique that can reduce some of the problems of rigid cast immobilisation
      and could potentially shorten the rehabilitation phase following injury.
      Information about the performance of these casts to assess their value in
      specific applications is very limited.

PMID- 12527244
TI  - Electromyographic and biomechanic analysis of anterior cruciate ligament
      deficiency and functional knee bracing.
AB  - OBJECTIVE: Examine the neuromuscular response to functional knee bracing relative
      to anterior tibial translations in vivo. DESIGN: During randomised brace
      conditions, electromyographic data with simultaneous skeletal tibiofemoral
      kinematics were recorded from four anterior cruciate ligament deficient subjects
      to investigate the effect of the DonJoy Legend functional brace during activity.
      BACKGROUND: Knee braces do not increase knee stability but may influence afferent
      inputs from proprioception and therefore one might expect changes in muscle
      firing patterns, amplitude and timing. METHODS: Hoffman bone pins affixed with
      markers were implanted into the tibia and femur for kinematic measurement. The
      EMG data from the rectus femoris, semitendinosus, biceps femoris, and lateral
      head of the gastrocnemius were integrated for each subject in three separate time
      periods: 250 ms preceding footstrike and two consecutive 125 ms time intervals
      following footstrike. RESULTS: With brace, semitendinosus activity significantly
      decreased 17% prior to footstrike whereas bicep femoris significantly decreased
      44% during A2, (P<0.05). Rectus femoris activity significantly increased 21% in
      A2 (P<0.05). No consistent reductions in anterior translations were evident.
      CONCLUSION: Our preliminary findings, based on a limited number of subjects,
      indicate joint stability may result from proprioceptive feedback rather than the
      mechanical stabilising effect of the brace. Despite a significant increase in
      rectus femoris activity upon landing, only one subject demonstrated an increase
      in anterior tibial drawer. RELEVANCE: Studies have shown functional braces do not
      mechanically stabilise the anterior cruciate ligament deficient knee. Perhaps
      bracing alters proprioceptive feedback. It has been shown that bracing the
      anterior cruciate ligament deficient knee may affect hamstring and quadriceps
      activity. Our findings stresses the importance of functional knee bracing
      combined with proprioceptive and muscular coordination training in order to
      increase joint stability.

PMID- 12527245
TI  - The effect of graft stiffness on knee joint biomechanics after ACL reconstruction
      -a 3D computational simulation.
AB  - OBJECTIVE: The objective was to determine the effect of varying graft stiffness
      and initial graft tension on knee kinematics and graft tension after anterior
      cruciate ligament reconstruction. DESIGN: A 3D computational knee model was used.
      BACKGROUND: Many factors influencing the biomechanical outcome of anterior
      cruciate ligament reconstruction have been investigated. However, there are no
      reports on the effect of variations in graft stiffness on knee behavior. METHODS:
      A 3D computational knee model was used to simulate anterior cruciate ligament
      reconstruction using three different grafts with stiffnesses similar to the
      anterior cruciate ligament (graft 1), a 10mm bone-patellar tendon-bone graft
      (graft 2), and a 14 mm bone-patellar tendon-bone graft (graft 3). The initial
      graft tension was set to 0 or 40 N with the knee at 30 degrees of flexion. A 134
      N anterior tibial drawer load and a 400 N quadriceps load were applied to the
      knee, and kinematics and graft tension were calculated. RESULTS: When fixed with
      no initial tension, graft 1 was found to under-constrain the knee, while graft 2
      slightly over-constrained the knee, and graft 3 over-constrained the knee when
      compared to the intact knee. When an initial graft tension of 40 N was used, all
      of the reconstructed knees were more constrained than when an initial tension of
      0 N was used. CONCLUSIONS: This study suggests that graft stiffness has a direct
      impact on knee biomechanics after anterior cruciate ligament reconstruction. An
      optimal anterior cruciate ligament reconstruction can be achieved if the anterior
      cruciate ligament is replaced by a graft with similar structural stiffness.
      RELEVANCE: This study showed that if the graft material and fixation sites are
      selected such that the anterior cruciate ligament structural stiffness is
      retained, normal knee kinematics can be restored.

PMID- 12527246
TI  - Cyclic joint loading can affect the initial stability of meniscal fixation
      implants.
AB  - OBJECTIVE: To identify the effect of cyclic joint loads on the initial fixation
      strength of different meniscal repair techniques. DESIGN: Three different
      meniscal refixation implants and one suturing technique were tested for initial
      stability in porcine knee joints after cyclic joint loading. BACKGROUND: Existing
      studies tested the initial pull out strength of meniscal fixation implants. It
      remains unknown how such implants perform under cyclic joint loading. METHODS:
      The Meniscal Fastener, the Meniscal Arrow, the ClearFix Screw, and a horizontal
      suture (PDS 1) were implanted in 64 porcine knee joints after setting a tear in
      the posterior horn of the medial meniscus. In one group of each device the
      menisci were excised directly after implantation and subsequently subjected to a
      pull out test. The knee joints of the other groups were exposed to 5000 axial
      load cycles between 10 and 200 N prior to the pull out test. RESULTS: The
      horizontal suture showed the highest pull out force (103 N, SD 19 N). Arrow (52
      N, SD 18 N), Meniscal Fastener (29 N, SD 3 N), and Meniscal Screw (22 N, SD 8 N)
      failed at significantly lower loads. Cyclic loading led to a decreased initial
      pull out force only for the horizontal suture (82 N, SD 26 N) and the Meniscal
      Fastener (23 N, SD 5N). CONCLUSIONS: Cyclic joint loading can lead to reduced
      fixation strength especially of meniscal refixation implants and sutures with
      relatively low stiffness. However, it remains unclear which fixation strength is
      necessary to provide conditions for meniscal healing. RELEVANCE: The current
      study adds information to the understanding of how meniscal fixation systems
      perform mechanically especially after cyclic joint loads.

PMID- 12527247
TI  - Determination of the effectiveness of materials in attenuating high frequency
      shock during gait using filterbank analysis.
AB  - OBJECTIVE: To develop an accurate method for quantifying the frequency content of
      the ground reaction force transient. DESIGN: Repeated measures design comparing
      the impact severity during walking with different insole materials. BACKGROUND:
      The body experiences a brief but sizeable impact upon heel strike during walking.
      This impact transient is believed to result in musculoskeletal injuries. It is
      important to accurately quantify this impact as a step towards decreasing the
      risk of injury. METHODS: Seven subjects walked barefoot at their normal cadence
      across a force platform, while insole materials (Spenco, Microcel-puff, and
      Plastazote) were placed on the surface of the force platform. A filterbank
      program was developed to determine the percent root mean square in 10 Hz
      frequency bands from zero to 400 Hz. Analysis focused on the impact transient
      contained in a 20 ms window after heel contact. RESULTS: The high frequency (>60
      Hz) power was significantly larger in the barefoot condition compared to the
      insole conditions. The barefoot condition also resulted in significantly higher
      initial peak forces and force loading rates. CONCLUSIONS: The frequency content
      of the ground reaction force can be effectively quantified using a filterbank
      approach. Shoe insole materials can reduce the initial peak force, force loading
      rate, and frequency content of the impact transient in walking. The frequency
      content of the initial ground reaction force extends up to 400 Hz in some
      footwear conditions. RELEVANCE: The new filterbank procedure illustrates that the
      vertical ground reaction force in walking has a higher frequency content than
      previously thought. This signal requires high sampling rates to avoid aliasing,
      and appropriate signal processing algorithms, such as filter banks, for analysis.

PMID- 12527248
TI  - Effects of stress deprivation on mechanical properties of the in situ frozen
      thawed semitendinosus tendon in rabbits.
AB  - OBJECTIVE: To clarify the effect of complete stress deprivation on the mechanical
      properties of the in situ frozen-thawed semitendinosus tendon, an idealized
      autograft model. DESIGN: Ninety-six rabbits were divided into three groups. In
      the frozen group (n=36), we applied the freeze-thaw treatment to the
      semitendinosus tendon to necrotize fibroblasts in the tendon. In the frozen and
      stress-shielded group (n=30), after we applied the same freeze-thaw treatment to
      the tendon, we completely released the tendon from stress. In the sham group
      (n=30), a sham operation was applied. In each group, 6 rabbits were sacrificed at
      0 (only in the frozen group), 1, 2, 3, 6 and 12 weeks after surgery. BACKGROUND:
      Previous studies have not clarified remodeling of the semitendinosus autograft in
      ligament reconstruction or its idealized model. METHODS: The tendon was frozen
      with liquid nitrogen. The tendon was released from stress with the originally
      developed technique using a polyester tape. In each period, 5 out of the 6
      rabbits were evaluated with tensile testing, and the remaining rabbit was
      histologically observed. RESULTS: Complete stress shielding significantly
      increased the cross-sectional area of the frozen-thawed tendon at 1 and 2 weeks,
      while it significantly inhibited the increase of the area due to the freeze-thaw
      treatment at 3 and 6 weeks. Complete stress shielding significantly reduced
      material properties of the frozen-thawed tendon after 2 weeks. CONCLUSIONS: The
      frozen-thawed semitendinosus tendon has unique remodeling characteristics under a
      stress-shielded condition, which were not the same as those of the frozen-thawed
      patellar tendon. RELEVANCE: Remodeling of the semitendinosus tendon autograft
      under stress-shielded conditions may be different from that of the patellar
      tendon autograft.

PMID- 12527249
TI  - Human temporomandibular joint disc cartilage as a poroelastic material.
AB  - OBJECTIVE: The hypothesis was tested that a poroelastic material model is
      potentially able to describe the mechanical behavior of cartilaginous tissues in
      dynamic indentation experiments.Design. This hypothesis was tested by comparing
      the results from model predictions with results obtained from cyclic indentation
      experiments. BACKGROUND: The characteristics of cartilaginous tissues in general
      and of the temporomandibular joint disc in particular are generally identified by
      static confined or unconfined indentation experiments, while under physiologic
      circumstances these tissues are mostly loaded dynamically. METHODS: Dynamic
      indentation experiments were simulated using an axisymmetric finite element
      model. The results from the simulations were qualitatively compared with the
      experiments. RESULTS: The simulations showed several similarities with the
      experiments when the solid matrix was assumed to be hyperelastic. Both the
      maximum stress and the amount of energy dissipated decreased in each subsequent
      cycle. Furthermore, a similar dependency on the indentation frequency and
      amplitude was found. CONCLUSIONS: This qualitative study showed that a
      poroelastic material model can describe the dynamic behavior of the
      temporomandibular joint disc, provided that the solid matrix is modeled as
      hyperelastic. RELEVANCE: Temporomandibular disorders are presumably related to
      joint load distributions. Besides large static, dynamic loads are considered as a
      risk factor for cartilaginous wear. Dynamical loads, however, are also considered
      to stimulate the biosynthetic activity of cartilaginous tissues. Biomechanical
      analysis can be applied to estimate nonmeasurable joint loads. This enables to
      understand the underlying mechanisms of temporomandibular disorders, necessary to
      develop methods to prevent, diagnose and cure joint disorders. The present study
      shows that a poroelastic material model can be applied successfully to model the
      dynamical behavior of the temporomandibular joint disc in such analyses.

PMID- 12527250
TI  - Influence of knee positions and gender on the Ober test for length of the
      iliotibial band.
AB  - OBJECTIVE: Examine the influence of knee positions and gender on the Ober test
      for the length of the iliotibial band. DESIGN: A cross-sectional comparative
      repeated measures design. BACKGROUND: The Ober test is in widespread use, yet the
      influence of knee positions and gender on the test has not been reported. Such
      information is needed to help clarify test results. METHODS: The Ober test was
      administered with the knee flexed to 90 degrees and extended to 0 degrees to the
      right lower limb of 26 women and 23 men. The limb was lowered from abduction and
      the end point of hip abduction (positive angle) or hip adduction (negative angle)
      was measured in relation to neutral. RESULTS: The hip adduction movement was
      restricted more with the knee flexed than with the knee extended for both genders
      (P<0.009). With the knee flexed the mean hip abduction angle was less for men (+4
      degrees) than for women (+6 degrees) (P<0.001), and with the knee extended the
      mean hip adduction angle was greater for men (-9 degrees) than for women (-4
      degrees) (P<0.001). CONCLUSIONS: The Ober test with the knee flexed limited hip
      adduction more than with the knee extended for both men and women, and women had
      greater limitations than men. RELEVANCE: The Ober test with the knee flexed and
      with the knee extended yielded different results and may be considered different
      tests. Normal Ober test values for the two knee positions should be defined
      separately for men and women in order to understand how deviations from normal
      are related to pathologies.

PMID- 12527251
TI  - Segmental mobility of the lumbar spine during a posterior to anterior
      mobilization: assessment using dynamic MRI.
AB  - OBJECTIVES: To quantify segmental mobility of the lumbar spine during a posterior
      to anterior spinal mobilization procedure. DESIGN: Descriptive study using
      dynamic magnetic resonance imaging. BACKGROUND: The posterior to anterior spinal
      mobilization procedure is frequently used in the assessment and management of
      spinal dysfunction. How this procedure influences segmental spinal motion
      however, is not known. METHODS: Eleven asymptomatic subjects were positioned
      prone within a vertically open double donut design magnetic resonance imaging
      system. An anteriorly directed force was applied manually at each lumbar spinous
      process while magnetic resonance images were obtained continuously in the
      sagittal plane. The intervertebral angle was used to quantify segmental motion.
      RESULTS: The direction of motion at the tested segment was always extension, with
      values ranging from 1.2 (SD 2.2) at L2 to 3.0 (SD 2.3) degrees at L5. When the
      force was applied at L3, L4 and L5, the non-tested (adjacent) segments also were
      observed to move into extension. However, when the posterior to anterior force
      was applied at L1 and L2 the three caudal segments moved into flexion.
      CONCLUSIONS: Posterior to anterior spinal mobilization consistently caused
      extension at the tested segment, while the motion of the collective lumbar spine
      was either an increase or decrease in lordosis depending on the segment at which
      the force was applied. RELEVANCE: Passive movement techniques are commonly used
      to identify the symptomatic lumbar segment(s) and can be used as a treatment
      aimed at increasing mobility and/or decreasing pain. Knowledge of how this
      procedure influences segmental motion of healthy spines is important in
      understanding how altered mobility is related to symptoms.

PMID- 12527253
TI  - In vitro cytotoxicity testing of polycations: influence of polymer structure on
      cell viability and hemolysis.
AB  - A comparative in vitro cytotoxicity study with different water-soluble, cationic
      macromolecules which have been described as gene delivery systems was performed.
      Cytotoxicity in L929 mouse fibroblasts was monitored using the MTT assay and the
      release of the cytosolic enzyme lactate dehydrogenase (LDH). Microscopic
      observations were carried out as indicators for cell viability. Furthermore,
      hemolysis of erythrocytes was quantified spectrophotometrically. To determine the
      nature of cell death induced by the polycations, the nuclear morphology after
      DAPI staining and the inhibition of the toxic effects by the caspase inhibitor
      zVAD.fmk were investigated. All assays yielded comparable results and allowed the
      following ranking of the polymers with regard to cytotoxicity:
      Poly(ethylenimine)=poly(L-lysine)>poly(diallyl-dimethyl-ammonium
      chloride)>diethylaminoethyl-dextran>poly(vinyl pyridinium bromide)>Starburst
      dendrimer>cationized albumin>native albumin. The magnitude of the cytotoxic
      effects of all polymers were found to be time- and concentration dependent. The
      molecular weight as well as the cationic charge density of the polycations were
      confirmed as key parameters for the interaction with the cell membranes and
      consequently, the cell damage. Evaluating the nature of cell death induced by
      poly(ethylenimine), we did not detect any indication for apoptosis suggesting
      that the polymer induced a necrotic cell reaction. Cell nuclei retained their
      size, chromatin was homogenously distributed and cell membranes lost their
      integrity very rapidly at an early stage. Furthermore, the broad spectrum caspase
      inhibitor zVAD.fmk did not inhibit poly(ethylenimine)-induced cell damage.
      Insights into the structure-toxicity relationship are necessary to optimize the
      cytotoxicity and biocompatibility of non-viral gene delivery systems.

PMID- 12527252
TI  - Coordination and stability of one-legged hopping patterns in patients with
      anterior cruciate ligament reconstruction: preliminary results.
AB  - OBJECTIVES: To investigate whether the intralimb coordination of the lower
      extremity during one-legged hopping in patients with anterior cruciate ligament
      reconstruction is different and less stable compared to control subjects. DESIGN:
      Measures of coordination dynamics are applied to study the coordination and
      stability of movement patterns of the knee and ankle in patients and control
      subjects. BACKGROUND: Due to several factors, such as loss of proprioceptive
      function and muscle weakness, the intralimb coordination of the lower extremity
      might be altered. METHODS: Seven patients and 13 healthy control subjects were
      instructed to hop in place on one leg for 10 seconds at a comfortable frequency
      for each leg separately. RESULTS AND CONCLUSIONS: The one-legged hopping movement
      pattern of patients with anterior cruciate ligament reconstruction one-year post
      operative is different and less stable compared to healthy subjects, and thus is
      still impaired. RELEVANCE: This paper shows that patients, one year after
      reconstruction of the anterior cruciate ligament, have a different coordination
      pattern of the lower limb compared to a matched control group. Intersegmental
      coordination and stability, features that are often observed by eye during a
      rehabilitation process, are objectified in this study.

PMID- 12527254
TI  - Chemically patterned, metal oxide based surfaces produced by photolithographic
      techniques for studying protein- and cell-surface interactions I:
      Microfabrication and surface characterization.
AB  - Chemical patterns on smooth wafer substrates comprising areas with two different
      metals have been produced by vacuum metal deposition and photolithographic
      techniques. The combination of metals has been chosen from the series titanium
      (Ti), aluminium (Al), vanadium (V) and niobium (Nb), producing patterns (dots and
      stripes with dimensions of 50, 100 and 150 micrometer) with one of the metals as
      the background and with the second metal (foreground pattern) deposited on the
      background metal. The structure and chemical composition of the patterned
      surfaces were evaluated by scanning electron microscopy, X-ray photoelectron
      spectroscopy and imaging time-of-flight secondary-ion mass spectrometry. The
      surfaces proved to be geometrically well defined with the expected surface
      chemical composition, i.e. a surface oxide (passive) film essentially composed of
      TiO(2),Al(2)O(3),V(2)O(5), or Nb(2)O(5). Ti/Ti patterned surfaces were produced
      as controls and found to show no chemical composition contrast. The surface
      roughness of the pattern was greater than that of the background by a factor of 2
      3, but was still extremely smooth with Ra<2nm. The patterns serve as model
      surfaces for studying in vitro the behaviour of cells as well as the adsorption
      of serum proteins on different metal oxides, which will be reported in a
      companion paper. These surfaces can be used to compare and contrast the response
      of osteoblasts to Ti and other alloy components, such as Al, V, or Nb, which are
      used in load-bearing medical implants.

PMID- 12527256
TI  - Interfacial fracture toughness between bovine cortical bone and cements.
AB  - To evaluate the bonding strength of the interfaces within the cemented
      arthroplasty system, various mechanical tests have been used. Conventional push
      out and pull-out tests cannot reveal the actual bonding property of the interface
      because of the significant influence of surface roughness on the measured
      adhesion and the failure to account for the mismatch of elastic modulus across
      the interface. An alternative fracture mechanics approach, which considers the
      mix of opening and shear modes of the crack tip loading associated with the
      testing system and the elastic mismatch of materials across the interface, was
      used to evaluate the bonding ability of various cements. The four-point bend
      interfacial delamination test by Charalambides et al. (J. Appl. Mech. 56 (1989)
      77; Mech. Mater. 8 (1990) 269) was used to quantify the bonding ability of
      cements. This method is arguably more suitable since the applied loading mode is
      comparable to the nature of loading within the prosthetic system, which is
      primarily bending. The bovine bone specimens were polished to mirror finish to
      eliminate bonding by mechanical interlocking. The results revealed minimal
      bonding for the conventional bone cement (PMMA) whereas substantial bonding was
      evident for the glass-ionomer cements tested. However, only the conventional
      glass-ionomer cements showed evidence of bonding on testing, while the resin
      modified glass-ionomer cement (poly-HEMA) did not. The latter appeared to debond
      before testing because of excessive expansion stresses associated with swelling
      in water.

PMID- 12527255
TI  - Chemically patterned, metal-oxide-based surfaces produced by photolithographic
      techniques for studying protein- and cell-interactions. II: Protein adsorption
      and early cell interactions.
AB  - Protein adsorption and adhesion of primary human osteoblasts on chemically
      patterned, metal-oxide-based surfaces comprising combinations of titanium,
      aluminium, vanadium and niobium were investigated. Single metal samples with a
      homogeneous surface and bimetal samples with a surface pattern produced by
      photolithographic techniques were used. The physical and chemical properties of
      the samples have been extensively characterised and are presented in a companion
      paper. Here, we describe their properties in terms of cell responses during the
      initial 24h of cell culture. Regarding the cell number and activity there was no
      significant difference between any of the single metal surfaces. However the
      morphology of cells on vanadium surfaces became spindle-like. In contrast to the
      behaviour on single metal samples, cells exhibited a pronounced reaction on
      bimetallic surfaces that contained aluminium. Cells tended to stay away from
      aluminium, which was the least favoured metal in all two-metal combinations. An
      initial cell alignment relative to the pattern geometry was detectable after 2h
      and was fully developed after 18h of incubation. The organisation of f-actin and
      microtubules as well as the localisation of vinculin were all more pronounced on
      non-aluminium regions. We hypothesised that the differences in cell response
      could be associated with differences in the adsorption of serum proteins onto the
      various metal oxides. Protein adsorption experiments were performed using
      microscopy in conjunction with immunofluorescent stains. They indicated that both
      fibronectin and albumin adsorption were significantly greater on the non
      aluminium regions, suggesting that differences in cellular response correlate
      with a modulation of the concentration of serum proteins on the surface.

PMID- 12527257
TI  - Preparation and characterization of biodegradable PLA polymeric blends.
AB  - The purpose of this study was to fine-tune the mechanical properties of high
      molecular-weight poly-L-lactic acid (PLLA), especially to increase its toughness
      without sacrificing too much of its original strength. Besides of its long
      degradation time, PLLA is usually hard and brittle, which hinders its usage in
      medical applications, i.e., orthopedic and dental surgery. Some modifications,
      such as the addition of plasticizers or surfactants/compatibilizers, are usually
      required to improve its original properties. PDLLA can degrade quickly due to its
      amorphous structure, thus shortening the degradation time of PLLA/PDLLA blends.
      Blends of biodegradable poly-L-lactic acid (PLLA) and poly-DL-lactic acid (PDLLA)
      or polycaprolactone (PCL), in addition to a third component, the surfactant-a
      copolymer of ethylene oxide and propylene oxide, were prepared by blending these
      three polymers at various ratios using dichloromethane as a solvent. The weight
      percentages of PLLA/PDLLA (or PCL) blends were 100%/0%, 80%/20%, 60%/40%,
      50%/50%, 40%/60%, 20%/80% and 0%/100%, respectively. Physical properties such as
      the crystalline melting point, glass transition point (T(g)), phase behavior,
      degradation behavior, and other mechanical properties were characterized by
      thermogravimetric analysis, differential scanning calorimetry (DSC), infrared
      spectroscopy, gel permeation chromatography, and dynamic mechanical analysis
      (DMA). DSC data indicate that PLLA/PDLLA blends without the surfactant had two
      T(g)'s. With the addition of the surfactant, there was a linear shift of the
      single T(g) as a function of composition, with lower percentages of PLLA
      producing lower glass transition temperatures indicating that better miscibility
      had been achieved. DMA data show that the 40/60 PLLA/PDLLA blends without the
      surfactant had high elastic modulus and elongation, and similar results were
      observed after adding 2% surfactant into the blends. The 50/50 PLLA/PDLLA/2%
      surfactant blend had the highest elastic modulus, yield strength, and break
      strength compared with other ratios of PLLA/PDLLA/2% surfactant blends. The
      elongation at break of 50/50 PLLA/PDLLA was similar to that of PLLA. Again, the
      elongation at break of 50/50 PLLA/PDLLA/2% surfactant was almost 1.2-1.9 times
      higher than that of 50/50 PLLA/PDLLA and PLLA. Elongation of PLLA increased with
      the addition of PCL, but the strength decreased at the same time. In conclusions,
      adding PDLLA and surfactant to PLLA via solution-blending may be an effective way
      to make PLLA tougher and more suitable to use in orthopedic or dental
      applications.

PMID- 12527258
TI  - Biodegradable micelles/polymersomes from fumaric/sebacic acids and poly(ethylene
      glycol).
AB  - Linear unsaturated oligo-anhydrides containing terminal acylchloride groups have
      been synthesized by polycondensation of fumaric or sebacic acid with either
      fumaryl chloride or sebacoyl chloride. Reaction of these oligo-anhydrides with
      poly(ethylene glycol) produce di- and tri-block copolymers. The oligo-anhydrides
      and block copolymers have been characterized by gel permeation chromatography
      (GPC), NMR and FT-IR spectroscopies. The tri-block copolymers composed of two PEG
      end blocks and an oligo-anhydride center block have been used in encapsulation of
      calcein (encapsulation efficiency up to 40%). Encapsulation and release profile
      of calcein (as a model hydrophilic drug) from the di-block copolymers (micelles)
      and tri-block copolymer vesicles (polymersomes) as well as their in-vitro
      hydrolytic degradation (pH=7.4 degrees C, 37 degrees C) are reported.

PMID- 12527259
TI  - Intracellular protein tyrosine phosphorylation of adherent human macrophages on
      adsorbed fibronectin.
AB  - Fibronectin (FN) was pre-adsorbed onto physicochemically distinct substrates:
      polyethyleneglycol-based networks or tissue culture polystyrene (TCPS). The role
      of these substrates in modulating FN-mediated intracellular protein tyrosine
      phosphorylation and cell adhesion was analyzed with human primary blood derived
      macrophages. Although macrophage adhesion on both FN-pre-adsorbed TCPS and
      networks was similarly dependent on protein tyrosine kinase (PTK) and protein
      serine/threonine kinase (PSK), the compensation between PTK and PSK, and the
      involvement of signaling molecules (such as protein kinase C (PKC) isoforms) were
      distinct between the substrates. The pattern and the extent of tyrosine
      phosphorylation of several proteins (i.e. approximately 70, approximately 44,
      approximately 30kDa) were differentially regulated by PKCs. FN-derived peptides
      were employed to probe this material-dependency in macrophage adhesion and
      tyrosine phosphorylation. The PHSRN domain in the peptide sequence was
      predominant in mediating this substrate-dependent FN signaling event. We conclude
      that the tyrosine phosphorylation and the cross talk between PTK and PSK are
      modulated by FN and the substrate onto which the protein is adsorbed.

PMID- 12527260
TI  - Effects of clinically relevant alumina ceramic wear particles on TNF-alpha
      production by human peripheral blood mononuclear phagocytes.
AB  - The recent introduction of microseparation of the components of ceramic-on
      ceramic hip prostheses during hip simulations has produced clinically relevant
      wear rates, wear patterns and wear particles. This provided an opportunity to
      determine the response of primary human peripheral blood mononuclear cells to
      clinically relevant alumina ceramic wear particles in vitro. Alumina ceramic wear
      particles were generated in a hip joint simulator under microseparation
      conditions. The particles showed a bi-modal size distribution with nanometer
      sized (5-20nm) and larger particles (0.2->10 micrometer). The particles were
      cultured with human peripheral blood mononuclear cells obtained from six
      different donors at particle volume to cell number ratios of 1, 10, 100 and 500
      micrometer(3). After 24h incubation the viability of the cells and the levels of
      TNF-alpha were determined. The response to the microseparation wear particles was
      compared to that of commercially available alumina powder with a uniform
      morphology and mean size of 0.5 micrometer. All six Donors PBMNC produced
      significantly elevated levels of TNF-alpha when stimulated with 100 micrometer(3)
      of the alumina powder per cell. Volumetric concentrations of 10 and 1.0
      micrometer(3) per cell failed to stimulate a significant response by the cells
      from any of the six donors. Three of the six Donors PBMNC secreted significantly
      elevated levels of TNF-alpha when stimulated with 100 micrometer(3) of the
      microseparation wear particles, whereas the other three failed to respond to the
      wear debris at this concentration. All of the Donors PBMNC produced significantly
      elevated levels of TNF-alpha when stimulated with 500 micrometer(3) of the
      microseparation wear particles per cell. Thus, a greater volume of the
      microseparation wear particles was required to activate the PBMNC than the
      alumina powder. This was probably due to the microseparation wear particles
      having fewer particles in the critical size range (0.1-1 micrometer) for
      macrophage activation compared to the alumina powder. It can be concluded that
      alumina ceramic wear particles generated under microseparation conditions are
      capable of inducing osteolytic cytokine production by human mononuclear
      phagocytes. However, the volumetric concentration of the particles needed to
      generate this response is extremely high and given the low wear rates (<4mm(3)
      per million cycles) of ceramic-on-ceramic bearings, even under severe
      microseparation conditions, it is unlikely that this concentration threshold will
      be achieved in vivo.

PMID- 12527261
TI  - In vitro reconstruction of human dermal equivalent enriched with endothelial
      cells.
AB  - Experiences coming from many cell-culture studies has brought about the concept
      that tissue and organ reconstruction should be performed in a three-dimensional
      environment as it normally occurs in vivo. As far as endothelial cell culture is
      concerned, it has been shown that angiogenesis can be successfully achieved only
      when cells are cultured in the presence of collagen-based matrices or basal
      membrane substrates. The aim of the present investigation is to demonstrate that
      human umbilical vein endothelial cells (HUVEC) can be grown and differentiated on
      an artificial dermis obtained by fibroblasts cultured on hyaluronic acid-based
      scaffolds. For this purpose, we have cultured HUVEC, retrieved by collagenase
      digestion of perfused human umbilical vein either alone and with fibroblast at
      1/1 ratio into HYAFF-11 non-woven mesh. Cultures were maintained for up to 3
      weeks. Samples were taken at different time points within this period for the MTT
      proliferation test and for immunohistochemical analysis. Our results demonstrate
      that hyaluronan-based biomaterials (HYAFF-11 NW mesh) represent a suitable
      substrate for HUVEC adhesion, proliferation and reorganization in microcapillary
      network.

PMID- 12527262
TI  - Extracellular matrix production by human osteoblasts cultured on biodegradable
      polymers applicable for tissue engineering.
AB  - The nature of the extracellular matrix (ECM) is crucial in regulating cell
      functions via cell-matrix interactions, cytoskeletal organization, and integrin
      mediated signaling. In bone, the ECM is composed of proteins such as collagen
      (CO), fibronectin (FN), laminin (LM), vitronectin (VN), osteopontin (OP) and
      osteonectin (ON). For bone tissue engineering, the ECM should also be considered
      in terms of its function in mediating cell adhesion to biomaterials. This study
      examined ECM production, cytoskeletal organization, and adhesion of primary human
      osteoblastic cells on biodegradable matrices applicable for tissue engineering,
      namely polylactic-co-glycolic acid 50:50 (PLAGA) and polylactic acid (PLA). We
      hypothesized that the osteocompatible, biodegradable polymer surfaces promote the
      production of bone-specific ECM proteins in a manner dependent on polymer
      composition. We first examined whether the PLAGA and PLA matrices could support
      human osteoblastic cell growth by measuring cell adhesion at 3, 6 and 12h post
      plating. Adhesion on PLAGA was consistently higher than on PLA throughout the
      duration of the experiment, and comparable to tissue culture polystyrene (TCPS).
      ECM components, including CO, FN, LM, ON, OP and VN, produced on the surface of
      the polymers were quantified by ELISA and localized by immunofluorescence
      staining. All of these proteins were present at significantly higher levels on
      PLAGA compared to PLA or TCPS surfaces. On PLAGA, OP and ON were the most
      abundant ECM components, followed by CO, FN, VN and LN. Immunofluorescence
      revealed an extracellular distribution for CO and FN, whereas OP and ON were
      found both intracellularly as well as extracellularly on the polymer. In
      addition, the actin cytoskeletal network was more extensive in osteoblasts
      cultured on PLAGA than on PLA or TCPS. In summary, we found that osteoblasts
      plated on PLAGA adhered better to the substrate, produced higher levels of ECM
      molecules, and showed greater cytoskeletal organization than on PLA and TCPS. We
      propose that this difference in ECM composition is functionally related to the
      enhanced cell adhesion observed on PLAGA. There is initial evidence that specific
      composition of the PLAGA polymer favors the ECM. Future studies will seek to
      optimize ECM production on these matrices for bone tissue engineering
      applications.

PMID- 12527263
TI  - Accelerated cell sheet recovery by co-grafting of PEG with PIPAAm onto porous
      cell culture membranes.
AB  - Fabrication of functional tissue constructs from designed three-dimensional
      structures of cells using the layered method of cultured cell sheets could prove
      to be an attractive approach to tissue engineering. Rapid recovery of cell sheets
      is considered to be important as a basic technology for practical assembly of
      tissue-mimicking structures. To accelerate required culture substrate
      hydrophilic/hydrophobic functional changes according to the hydrated/dehydrated
      structural changes in response to culture temperature alteration, poly(N
      isopropylacrylamide) (PIPAAm) was grafted with poly(ethylene glycol) (PEG) onto
      porous culture membranes by electron beam irradiation. Analyses by attenuated
      total reflection-Fourier transform infrared and electron spectroscopy for
      chemical analysis revealed that PIPAAm and PEG were successfully grafted to
      surfaces of porous membranes. PIPAAm-grafted porous membranes (PIPAAm-PM) were
      compared with porous membranes co-grafted with various amounts of PEG and PIPAAm
      (PIPAAm(PEG)-PM) for cell sheet detachment experiments. Approximately 35min
      incubation at 20 degrees C was required to completely detach cell sheets from
      PIPAAm-PM in a static condition, while only 19min to detach cell sheets from
      PIPAAm(PEG0.5%)-PM, which is co-grafted with PIPAAm and 0.5wt% of PEG. With
      porous membranes, water molecules were accessed by the PIPAAm molecules grafted
      on the surfaces from both underneath and peripheral to the attached cell sheet,
      resulting in more rapid hydration of grafted PIPAAm molecules and detachment of
      cell sheet than that for nonporous tissue culture polystyrene (TCPS) dish. With
      PIPAAm(PEG)-PMs, grafted PEG chains should accelerate the diffusion of water
      molecules to PIPAAm grafts, showing more rapid detachment of cell sheet compare
      to PIPAAm-PMs.

PMID- 12527264
TI  - Influence of scaffold thickness and scaffold composition on bioartificial graft
      survival.
AB  - Biological scaffolds exhibit advantageous properties for tissue engineering of
      small diameter vessels. The influence of their extracellular matrix (ECM)
      components during in vivo repopulation is unknown. We implanted different
      xenogenic vascular matrices in a rat model to determine the influence of scaffold
      thickness and ECM composition on in vivo repopulation. Decellularized ovine
      jugular vein (JV, n=42), carotid artery (CA, n=42) and aorta (AO, n=42) were
      implanted subcutaneously in the neck of adult male rats. Animals were sacrificed
      2, 4 and 8 weeks after implantation. Cell and matrix morphology of explanted
      scaffolds were characterized by hematoxylin-eosin and pentachrome staining.
      Monoclonal anti-rat-CD31 was used to identify revascularization. Quantification
      of cell density was done by DNA-isolation. THICKNESS OF IMPLANTED XENOGENIC
      SCAFFOLDS VARIED ACCORDING TO THE MATERIAL USED (AO: 3.0-3.8mm; CA: 0.7-0.88mm;
      JV: 0.35-0.61mm). Immunohistology revealed complete repopulation of AO, CA, and
      JV scaffolds with endothelial cells and myofibroblasts within 2 weeks. After 8
      weeks of implantation, AO scaffolds were completely covered by an endothelial
      monolayer and showed signs of a central matrix degeneration. JV scaffolds were
      completely degenerated at this stage. In contrast, CA scaffolds showed preserved
      ECM with a normal myofibroblast population and endothelial cell coverage.

PMID- 12527265
TI  - A biological hybrid model for collagen-based tissue engineered vascular
      constructs.
AB  - Various approaches to tissue engineering a small diameter blood vessel have
      historically relied upon extended culturing periods and/or synthetic materials to
      create mechanical properties suitable to withstand the hemodynamic stresses of
      the vasculature. In this work, we present the concept of a construct-sleeve
      hybrid (CSH) graft, which uses a biological support to provide temporary
      reinforcement while cell-mediated remodeling of the construct occurs. Support
      sleeves were fabricated from Type I collagen gels and crosslinked with
      glutaraldehyde, ultraviolet, or dehydrothermal treatments. Uniaxial tensile
      testing of acellular sleeves revealed increased stiffness moduli and tensile
      stresses with crosslinking treatments. A second collagen layer containing cells
      was molded about the sleeve to create a CSH. After in vitro culture, CHSs with
      uncrosslinked (UnXL) and glutaraldehyde treated (Glut) sleeves exhibited
      significant increases in mechanical strength (20.4-fold and 121-fold increases in
      ultimate stress, respectively) compared to unreinforced control constructs. Burst
      testing produced similar findings with peak pressures of 100 and 650mmHg in the
      UnXL and Glut CSHs, respectively. Construct compaction, cell viability, and
      histological examination demonstrated that the function of most cells remained
      unimpaired with the incorporation of the biological support sleeve.

PMID- 12527266
TI  - Mesenchymal stem cells, MG63 and HEK293 transfection using chitosan-DNA
      nanoparticles.
AB  - Chitosan-DNA nanoparticles were synthesized from the complexation of the cationic
      polymer with a ss-gal DNA plasmid, in order to study the efficacy of chitosan to
      develop a non-viral gene delivery system that can be optimized for efficient gene
      therapy. The optimal binding conditions were determined with the fluorescamine
      and PicoGreen assays. DNA distribution within the nanoparticle was visualized by
      electron transmission microscopy, while the size and morphology were assessed by
      atomic force microscopy. The transfection potential was evaluated for the first
      time on human mesenchymal stem cells (MSCs), on human osteosarcoma cells (MG63)
      and on human embryonic kidney cells (HEK293). The LipofectAMINE(TM) 2000 (LF)
      reagent was used in comparison. The effect of chitosan-DNA nanoparticles on cell
      viability was illustrated with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromide (MTT) assay. The nanoparticles formed are of a diameter
      inferior to 100nm with a homogenous distribution of DNA. The transfection of
      HEK293 cells is superior to that seen with MG63 cells and MSCs, however not
      surpassing that seen with LF. Minimal cytotoxicity is seen with the polyplexes
      compared to greater than 50% toxicity with LF. These results suggest that
      chitosan-DNA nanoparticles have favorable characteristics for non-viral gene
      delivery, are cell type dependent and not cytotoxic.

PMID- 12527267
TI  - Calcium-deficient apatite: influence of granule size and consolidation mode on
      release and in vitro activity of vancomycin.
AB  - The use of dynamic compaction and isostatic compression to consolidate calcium
      phosphate powder loaded with a therapeutic agent avoids a sintering step that
      could destroy the drug. The present study applied these consolidation methods to
      vancomycin-loaded calcium-deficient apatite powder, using three granulometric
      fractions (40-80, 80-200 and 200-500 micrometer). In vitro release profiles were
      determined via an original system derived from low-pressure liquid
      chromatography. The biological activity of vancomycin was measured by an in vitro
      standardized bacteriologic assay, which showed that the drug is completely active
      after association with calcium phosphate. Regardless of the consolidation method
      and granulometric fraction used, release profiles were not significantly
      different and therefore adaptable to injectable suspensions.

PMID- 12527268
TI  - Design of physostigmine-loaded polymeric microparticles for pretreatment against
      exposure to organophosphate agents.
AB  - Physostigmine is an anti-cholinesterase used for the pretreatment of a poisoning
      caused by highly toxic organophosphorus neurotoxins. The aim of this study is to
      design a polymeric microparticle system for sustained release of physostigmine.
      In this paper, we have attempted to encapsulate physostigmine in microparticles
      made from poly(D,L-lactide-co-glycolide) (PLGA) with various contents of
      glycolide and poly(D,L-lactide) (PLA) using spray-drying and single emulsion
      techniques. It was found that during the single emulsion process, most of the
      physostigmine molecules were lost in the external aqueous phase. However, more
      than 90% encapsulation efficiency of physostigmine was obtained using the spray
      drying technique. SEM micrographs revealed that spherical microparticles
      containing physostigmine with a smooth surface were yielded with PLA, PLGA 50:50,
      RG 502 (PLGA 50:50 with a lower molecular weight) and PLGA 65:35 but PLGA 85:15,
      PLGA 75:25 and PLGA 50:50 with a high concentration produced microparticles with
      irregular shapes. An increased inlet temperature yielded a higher physostigmine
      release rate from the PLA microparticles. Physostigmine release from the
      microparticles showed a biphasic pattern, characterized by an initial burst
      release followed by a sustained release for PLGA 65:35, PLGA 50:50 and RG 502 or
      a non-detectable release for PLGA 85:15, PLGA 75:25 and PLA. A sustained-release
      of physostigmine with a low initial burst over 1 week was achieved from RG 502
      microparticles, which would be used as an injectable dosage form in our further
      animal studies.

PMID- 12527269
TI  - Mechanical behaviour and biocompatibility of poly(1-vinyl-2-pyrrolidinone)
      gelatin IPN hydrogels.
AB  - IPN hydrogels based on poly(1-vinyl-2-pyrrolidinone) and gelatin were obtained by
      casting of aqueous solution using potassium persulphate and glutaraldehyde as
      respective crosslinking agents. Studies of swelling and mechanical behaviour
      showed that the samples of different composition can incorporate high content of
      water and still exhibit high compression strength. The composition has influence
      at the global crosslinking density what affects the mechanical performance. In
      vitro biocompatibility and hemocompatibility were also investigated. The
      materials do not interfere on the cellular functions and neither induce platelet
      adhesion. From this preliminary evaluation, it is possible to conclude that these
      hydrogels have potential for applications in the biomedical field.

PMID- 12527270
TI  - Mechanical and thermal properties of novel polymerized NDGA-gelatin hydrogels.
AB  - Nordihydroguaiaretic acid (NDGA), an antioxidant with two functional ortho
      catechols from the creosote bush, has been shown to increase the mechanical
      properties of synthetic collagen fibers, producing biologically based,
      biocompatible fibers with material properties in uniaxial tensile tests to
      failure that are comparable to those of native tendon (Koob and Hernandez,
      Biomaterials 23 (2002) 203; Koob et al., J Biomed Mater Res, 56 (2001) 31; 56
      (2001) 40). The NDGA polymerization scheme was applied to gelatin hydrogels to
      determine whether it could provide a viable approach for producing gelatin based
      biological materials with advantageous mechanical and thermal properties. NDGA
      treatment eliminated gelatin solubilization from hydrogels in chaotropic agents
      and increased the thermal stability of gelatin hydrogels from less than 37
      degrees C to over 80 degrees C. NDGA caused a dose dependent increase in the
      compressive stiffness and fracture load of gels ranging in concentration from
      2.5% to 40% gelatin in uniaxial, unconfined compression tests to failure. Maximum
      fracture load averaged 0.5+/-0.1MPa and the compressive modulus averaged 4.4+/
      1.4MPa for all gelatin concentrations, however, the concentration of NDGA that
      produced maximum strength and stiffness varied inversely with gelatin
      concentration. The compressive strength and stiffness of 5% gelatin hydrogels
      treated with NDGA were independent of temperature up to 52 degrees C. These
      results indicate that NDGA polymerization renders gelatin hydrogels thermally and
      mechanically stable and thereby potentially useful for surgical procedures that
      would benefit from biocompatible, stable and mechanically competent gelatin-based
      biomaterials.

PMID- 12527271
TI  - Fluoride controlled release tablets for intrabuccal use.
AB  - We have developed a fluoride controlled release delivering system for intrabuccal
      use, permitting to reach high enough local concentrations for desirable
      therapeutic effect with minimal side effects. We have formulated tablets of 160
      200mg intended to be fixed on a tooth. The tablets have a granular matrix
      composed of pure hydroxyapatite, Eudragit((R)) and/or ethylcellulose. NaF is
      added either by a mechanical mixing or an impregnation method. Profiles of
      continuous in vitro drug release in saline phosphate buffered solution were
      recorded by means of a fluoride selective electrode. Linear profiles are observed
      when ethylcellulose is used. The most reproducible results are obtained when the
      impregnation method is used. Eudragit((R)) increases the dissolution efficiencies
      while ethylcellulose decreases it.

PMID- 12527272
TI  - The effects of adding fluoride compounds to a fluoride-free glass ionomer cement
      on subsequent fluoride and sodium release.
AB  - Studies have shown that ions in a glass ionomer matrix are 1-10% of the amounts
      present in the original glass. To measure more precisely the release from a
      cement matrix, known amounts of ions were added to LG30 glass which was fluoride
      and sodium-free. Cement without additions acted as the control. 1.4-1.6% of each
      of sodium, calcium and aluminum fluorides were added to three portions of control
      blend. The sodium and fluoride release into deionised water from five discs of
      each cements blend was measured for 8 months. This represented complete release
      for sodium but not for fluoride. Traces of fluoride and sodium in the glass
      produced low but measurable amounts indicating about a third of the fluoride and
      substantially all sodium present in LG30 was released. The addition of calcium
      fluoride had no significant effect on sodium or fluoride release and aluminium
      fluoride minimal effects. Adding sodium fluoride significantly enhanced release
      of both ions although fluoride release was less than from a glass containing 5%
      fluoride. Only small proportions of the additions, 2-5% of the fluoride and 13%
      of sodium, were released. Sodium and fluoride appeared to be released
      independently. For LG30 cements additives were poor at supplying extra ions.

PMID- 12527274
TI  - The fluorapatite-anorthite system in biomedicine.
AB  - Glasses and glass ceramics of fluorapatite-anorthite (eutectic composition) were
      produced and characterized in order to evaluate their potential application in
      biomedicine. Bio-reactivity was determined by in vitro tests by immersion of
      powders in simulated plasma liquids as well as by in vivo experiments by
      implantation in rabbits. According to the results, the investigated materials are
      bio-acceptable since no toxic or other harmful evidence was detected. Glass
      ceramics showed remarkable inertness, whereas glasses spontaneously dissolved in
      SBF and after 1 week moderate formation of apatite was observed, that however
      ceased within a month.

PMID- 12527273
TI  - Detachment of titanium and fluorohydroxyapatite particles in unloaded endosseous
      implants.
AB  - The shape, surface composition and morphology of orthopaedic and endosseous
      dental titanium implants are key factors to achieve post-surgical and long-term
      mechanical stability and enhance implant osteointegration. In this study a
      comparison was made between 12 titanium screws, plasma-spray-coated with titanium
      powders (TPS), and 12 screws with an additional coating of fluorohydroxyapatite
      (FHA-Ti). Screws were implanted in the femoral and tibial diaphyses of two
      mongrel sheep and removed with peri-implant tissues 12 weeks after surgery. The
      vibrational spectroscopic, ultrastructural and morphological analyses showed good
      osteointegration for both types of implants in host cortical bone. The portion of
      the FHA-Ti implants in contact with the medullary canal showed a wider area of
      newly formed peri-implant bone than that of the TPS implants. Morphological and
      EDAX analyses demonstrated the presence of small titanium debris in the bone
      medullary spaces near the TPS surface, presumably due to the friction between the
      host bone and the implant during insertion. Few traces of titanium were detected
      around FHA-Ti implants, even if smaller FHA debris were present. The present
      findings suggest that the FHA coating may act as a barrier against the detachment
      of titanium debris stored in the medullary spaces near the implant surface.

PMID- 12527275
TI  - A natural compound (reuterin) produced by Lactobacillus reuteri for biological
      tissue fixation.
AB  - The study was undertaken to examine the degree of tissue fixation by reuterin, a
      natural compound produced by Lactobacillus reuteri, at distinct fixation
      conditions (pH, temperature, and fixative concentration). Additionally, the rate
      of tissue fixation by reuterin was investigated using glutaraldehyde as a
      control. It was found by the Fourier transformed infrared spectroscopy and
      nuclear magnetic resonance spectroscopy that both mono- and di-aldehyde reuterin
      oligomers may be present in the acidic and basic aqueous reuterin solutions.
      Therefore, reuterin may crosslink biological tissues as glutaraldehyde (a di
      aldehyde agent). The degree of tissue fixation by reuterin is significantly
      affected by its fixation conditions. Generally, with increasing the pH,
      temperature, or fixative concentration, the reduction in free-amino-group
      content, denaturation temperature, tensile strength, and resistance against
      enzymatic degradation of the reuterin-fixed tissue increased significantly. Also,
      the rate of tissue fixation by reuterin is significantly slower than that by
      glutaraldehyde. However, after fixation, it was noted that the reuterin-fixed
      tissue has comparable free-amino-group content, denaturation temperature, tensile
      strength, and resistance against enzymatic degradation as the glutaraldehyde
      fixed tissue.

PMID- 12527276
TI  - A comparative study between in vivo bone ingrowth and in vitro apatite formation
      on Na2O-CaO-SiO2 glasses.
AB  - This study compared in vivo bioactivity with the in vitro apatite-forming ability
      of biomaterials. Granules of five kinds of P(2)O(5)-free Na(2)O-CaO-SiO(2)
      glasses, showing different apatite-forming ability in simulated body fluid (SBF),
      were implanted into a defect on the femoral condyle of rabbits. Bone ingrowth was
      evaluated using scanning electron microscopy among five kinds of glasses at 1, 2,
      3, 6, and 12 weeks. Quantitative analysis was performed measuring the depth of
      new bone ingrowth from the periphery. In addition, the total areas of newly
      formed bone among glass particles were examined at 3 and 6 weeks using confocal
      laser scanning microscopy (CLSM) after weekly administration of fluorescent
      calcein. The depth of bone ingrowth among glass particles increased in proportion
      to their apatite-forming ability in vitro. The CLSM study showed a correlation
      between the quantities of labeled newly formed bone and in vitro apatite-forming
      ability. In the P(2)O(5)-free Na(2)O-CaO-SiO(2) glasses, the periods within 3-6
      days for inducing apatite in SBF considered a necessary condition to convey
      bioactivity in vivo, and in vivo evaluations at 2-3 weeks is important to
      determine this. The in vivo bioactivity was precisely reproduced by apatite
      forming ability in SBF. Therefore, evaluating apatite formation in SBF is a good
      screening test for the in vivo bioactivity of materials, resulting in reduction
      of the need for animal sacrifices and savings in experimental time.

PMID- 12527277
TI  - Apatite-forming ability and mechanical properties of CaO-free poly(tetramethylene
      oxide) (PTMO)-TiO2 hybrids treated with hot water.
AB  - Poly(tetramethylene oxide) (PTMO)-TiO(2) hybrids were prepared by a sol-gel
      method from triethoxysilane-functionalized PTMO (Si-PTMO) and
      tetraisopropyltitanate with weight ratios of 30/70, 40/60 and 50/50 (hybrids
      PT30, PT40 and PT50, respectively), and subsequently subjected to a hot-water
      treatment at 95 degrees C for 2 d. All the obtained hybrids were amorphous before
      the hot-water treatment, and precipitated nanosized anatase after the hot-water
      treatment. The amount of precipitated anatase increased with decreasing PTMO
      content. Apatite was not formed on the surfaces of the hybrids in a simulated
      body fluid before the hot-water treatment, but was formed after the hot-water
      treatment, and its amount increased with decreasing PTMO content. Hybrid PT40
      showed strength and Young's modulus analogous to those of human cancellous bones,
      and high ductility after the hot-water treatment. This kind of hybrid is expected
      to be useful as a new type of bone-repairing material.

PMID- 12527278
TI  - Prediction of multiaxial mechanical behavior for conventional and highly
      crosslinked UHMWPE using a hybrid constitutive model.
AB  - The development of theoretical failure, fatigue, and wear models for ultra-high
      molecular weight polyethylene (UHMWPE) used in joint replacements has been
      hindered by the lack of a validated constitutive model that can accurately
      predict large deformation mechanical behavior under clinically relevant,
      multiaxial loading conditions. Recently, a new Hybrid constitutive model for
      unirradiated UHMWPE was developed Bergstrom et al., (Biomaterials 23 (2002) 2329)
      based on a physics-motivated framework which incorporates the governing micro
      mechanisms of polymers into an effective and accurate continuum representation.
      The goal of the present study was to compare the predictive capability of the new
      Hybrid model with the J(2)-plasticity model for four conventional and highly
      crosslinked UHMWPE materials during multiaxial loading. After calibration under
      uniaxial loading, the predictive capabilities of the J(2)-plasticity and Hybrid
      model were tested by comparing the load-displacement curves from experimental
      multiaxial (small punch) tests with simulated load-displacement curves calculated
      using a finite element model of the experimental apparatus. The quality of the
      model predictions was quantified using the coefficient of determination (r(2)).
      The results of the study demonstrate that the Hybrid model outperforms the J(2)
      plasticity model both for combined uniaxial tension and compression predictions
      and for simulating multiaxial large deformation mechanical behavior produced by
      the small punch test. The results further suggest that the parameters of the HM
      may be generalizable for a wide range of conventional, highly crosslinked, and
      thermally treated UHMWPE materials, based on the characterization of four
      material properties related to the elastic modulus, yield stress, rate of strain
      hardening, and locking stretch of the polymer chains. Most importantly, from a
      practical perspective, these four key material properties for the Hybrid
      constitutive model can be measured by relatively simple uniaxial tension or
      compression tests.

PMID- 12527279
TI  - Water absorption of poly(methyl methacrylate) containing 4-methacryloxyethyl
      trimellitic anhydride.
AB  - The amount of water absorption of poly(methyl methacrylate) (PMMA) containing 0,
      1, 3 and 5 wt% of an adhesive monomer, 4-methacryloxyethyl trimellitic anhydride
      (4-META), was measured at 7 degrees C, 37 degrees C and 60 degrees C. After the
      water uptake reached equilibrium in specimens, they were desorbed to obtain a
      constant value and the absorption process was repeated. Mass changes in the
      second desorption were recorded for the storage temperatures of 37 degrees C and
      60 degrees C. Multiple regression analyses were conducted on three independent
      variables, 4-META concentration, storage temperature and absorption-desorption
      cycle. A statistically significant relationship was found between the maximum
      water uptake and 4-META concentration, while there was no relationship between
      the maximum water uptake and diffusion coefficient obtained using the Fick's law.
      The negative relationship in the latter did not support the free space theory.
      The significant and positive relationship between the maximum water uptake and 4
      META concentration demonstrates that water molecules diffuse through the
      formation of a hydrogen bond at polar sites. The maximum water uptake was not
      influenced by temperature, while the diffusion coefficient increased with the
      rise in temperature. The activation energy was 41-47 and 50-53 kJ/mol in the
      first and second absorption tests, respectively.

PMID- 12527280
TI  - Synthesis of Si, Mg substituted hydroxyapatites and their sintering behaviors.
AB  - Si, Mg-substituted hydroxyapatites, alone and co-substituted, have been prepared
      to obtain biomaterials having an improved biocompatibility. From FT-IR, XRD and
      ICP analyses, it was confirmed that single phases of hydroxyapatite substituted
      by Si alone or co-substituted by Si, Mg. The XRD data indicated the absence of
      extra phases related to silicon and magnesium oxide or other calcium phosphate
      species. Si-substituted hydroxyapatite of up to 2 wt% for Si and Si, Mg co
      substituted hydroxyapatite of 1 wt% for the each ion keep their original
      structures intact for the sintering temperatures of up to 1200 degrees C.
      However, it is observed that ion substitutions by an amount higher than the above
      ratios for each hydroxyapatite lead to destabilization of original structures of
      the hydroxyapatite and to the production of tricalcium phosphate and calcium
      phosphate silicate phases when the samples were sintered at 1100 degrees C or
      higher.

PMID- 12527281
TI  - Image analysis measurements of roughness by texture and fractal analysis
      correlate with contact profilometry.
AB  - Surface properties of a biomaterial are important factors that govern in part its
      biocompatibility. Among them, surface roughness is now recognized as a very
      important factor for cell interactions. Surface roughness (Ra) is routinely
      measured by contact profilometry but other methods are presently usable. We
      compared two methods (contact profilometry and image analysis of scanning
      electron microscopic images SEM) on a series of 12 titanium test pieces. The
      texture analysis of SEM pictures was done by the heterogeneity and run-length
      methods. Fractal geometry was also used with the "skyscraper" and "blanket"
      methods providing respectively the D(SKY) and D(BLANK) fractal dimensions. The
      fractal dimension of the profilometric curve was also computed (D(MINK)).
      Computer-simulated textures were used to evaluate the pertinence of the
      algorithms. A significant correlation was found between Ra and all the texture
      descriptors except heterogeneity. The correlation coefficient was dependent on
      the microscopic magnification. The fractal dimension of the curve was correlated
      with D(SKY) and D(BLANK). Run-length, D(SKY) and D(BLANK) were highly correlated,
      independent of the magnification used, a finding related to the self-similarity
      of the images. Image texture analysis can be a useful alternative to profilometry
      with brittle or soft materials or with objects having a complex shape.

PMID- 12527282
TI  - Competitive adsorption of serum proteins at microparticles affects phagocytosis
      by dendritic cells.
AB  - Serum protein adsorption to the surface of particulate synthetic drug carrier
      systems has a major influence on their uptake by phagocytes. The influence of
      alpha2-human serum glycoprotein (alpha2GP) on the phagocytosis of various surface
      modified microparticles was studied in dendritic cells (DC) and was compared with
      a potent opsonin, IgG, and a dysopsonin, human serum albumin (HSA). The
      microparticles were administered to DC before and after the incubation with
      alpha2GP, IgG and HSA in single, binary or ternary protein systems and in whole
      blood serum. Phagocytosis of microparticles was vastly affected by the surface
      character of the microparticles themselves and by the adsorption of the proteins.
      Poly-L-lysine (PLL)-modified microparticles were under all conditions
      internalized with highest efficiency which is suggested to be mediated by their
      positive surface charge. The adsorption of commonly phagocytosis promoting
      proteins reduced the uptake of PLL-modified particles and is explained by
      compensation of the positive surface charge by the adsorbed negatively charged
      proteins. In all other particle types tested, freshly adsorbed alpha2GP was found
      to exhibit a strong phagocytosis promoting activity which was comparable to that
      of adsorbed IgG. Interestingly, this opsonic activity was lost already 2 h after
      adsorption to the particle surface. Protein adsorption from binary and ternary
      protein systems and from whole blood serum occurred in a competitive manner.
      Significant inhibition of phagocytosis was observed, even when HSA was combined
      with strong opsonins such as alpha2GP or IgG or in mixtures of all three
      proteins, indicating the importance of studying the influence of protein
      adsorption in protein mixtures.

PMID- 12527283
TI  - In vitro evaluation of the inflammatory activity of ultra-high molecular weight
      polyethylene.
AB  - To understand the inflammatory potential of oxidised ultra high molecular weight
      polyethylene (ox-UHMWPE) compared with the virgin one (UHMWPE), we analysed in
      vitro the predisposition of their interaction with plasma proteins and cells
      involved in the inflammatory response. The adsorption on the surface of the two
      materials of adhesion proteins (Fibronectin and Albumin), and pro-inflammatory
      proteins (IgG and IgA) have been studied. Moreover, we have evaluated the
      materials effect on complement activation and on macrophages and monocytes
      neutrophils behaviour. The two UHMWPE chemical forms adsorbed all the proteins
      studied; the only difference was in complement activation. Enzyme immunoassay
      results evidenced higher levels of factor Bb and iC3b in plasma after the contact
      with the oxidised form. Physico-chemical properties of the oxidised UHMWPE
      affected the attachment of the cells as demonstrated by macrophages adhesion
      experiments. UHMWPE favoured only a limited peritoneal macrophages (PMs)
      spreading (round-shaped cells); the cell spreading and presence of microvilli on
      the cell membranes was evident in the case of the oxidised form, suggesting the
      activation of these cells on this chemical form. Ox-UHMWPE evidenced a
      statistically significative increase in chemiluminescence values respect to human
      unstimulated peripheral blood mononuclear cells, an index of increased cell
      release of reactive oxygen metabolites. In conclusion, UHMWPE oxidative
      degradation with its chemical modification induces monocytes-neutrophils
      chemiluminescence activation and PMs morphology changes correlated with
      macrophage activation, data consistent with the complement activation results
      obtained in this study; such modifications, along with changes in mechanical
      properties, are related to implant failure.

PMID- 12527284
TI  - A three-dimensional finite element model of the polymerization process in dental
      restorations.
AB  - Restoration of dental restorations with resin composite is hampered by shrinkage
      of the material during the polymerization process. In this study, we simulated
      the polymerization process in a detailed three-dimensional finite element model
      of a human upper premolar with a cusp-replacing restoration. It was analyzed how
      the stress patterns changed during polymerization and it was assessed whether
      immediate failure of the restoration is likely to occur and if so, which
      locations within the restoration are at highest risk and what the clinical
      implications of these findings are for clinical practice. It was found that the
      stresses increased rapidly during polymerization and decreased again in the post
      polymerization phase. At the interface, tensile stresses relaxed to a higher
      degree than the shear stresses. Stress values in the composite material and at
      the interface with the tooth tissue were lower than the reported strength values
      suggesting that immediate failure is unlikely. The safety factor against
      mechanical failure of the interface, however, was relatively low indicating that
      the interface between the composite material and the tooth tissue is at a higher
      risk for failure than the bulk of the restoration. Stress relaxation was less
      effective in areas where the interface surface was irregular. In common practice,
      irregular interface surfaces are used to increase the retention of the
      restoration. This study indicates that the increased retention may be compromised
      to some extent by higher shrinkage stresses. The fact that stresses considerably
      decreased during the post-polymerization period suggests that mechanical loading
      should be limited during the first few hours after restoration.

PMID- 12527285
TI  - Mechanism of bone-like formation on a bioactive implant in vivo.
AB  - The physical and chemical nature of the remodelled interface between the porous
      A3 glass-ceramic, composed of (wt%): SiO(2) = 54.5; CaO = 15.0; Na(2)O = 12.0;
      MgO = 8.5; P(2)O(5) = 6.0 K(2)O = 4.0, and the surrounding bone was studied after
      implantation into rat tibias. The interfaces which developed new bone layer in
      direct contact with the implants were examined by analytical scanning and
      transmission electron microscopy after implantation for 6, 8 and 12 weeks.
      Degradation processes of the implants also encouraged osseous tissue ingrowths
      into the pores of the material, changing drastically the macro- and
      microstructure of the implants. The ionic exchange initiated at the implant
      interface with the physiological environment was essential in the integration
      process of the implant, through a dissolution-precipitation-transformation
      mechanism. The interfaces developed non-toxic biological and chemical activities
      and remained reactive over the 12-week implantation period. These findings were
      significant as indicative of morphological and chemical integration of the A3
      glass-ceramic into the structure of living bone tissue. A3 glass-ceramic could be
      suitable for the repair or replacement of living bone.

PMID- 12527286
TI  - Metal ions induce bone-resorbing cytokine production through the redox pathway in
      synoviocytes and bone marrow macrophages.
AB  - To evaluate the biological reactions to metal ions potentially released from
      prosthetic implants, we examined the ability of metal ions to produce bone
      resorbing cytokines and the underlying mechanism using synoviocytes and bone
      marrow (BM) macrophages. The cells were incubated with NiCl(2), CoCl(2), CrCl(3)
      or Fe(2)(SO(4))(3) at optimal concentrations, which are detectable in joint fluid
      following total joint arthroplasty. The production of interleukin-1beta,
      interleukin-6 and tumor necrosis factor-alpha were enhanced by all metal ions
      tested as determined by enzyme-linked immunosorbent assay. From the results of
      electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding
      activity of nuclear factor kappaB (NF-kappaB), and p50-p65 heterodimers and p50
      homodimers were the major subunits. These effects of the metal ions were
      considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical
      scavenger. An electron spin resonance study clearly demonstrated the ability of
      metal ions to generate activated oxygen species (AOS), especially hydroxyl
      radicals (*OH), which accounts for PDTC-blockade of metal ion-induced NF-kappaB
      activation and subsequent cytokine production. Taken together, our data raised
      the possibility that small amounts of metal ions released from prosthetic
      implants activate synoviocytes and BM macrophages through the AOS-mediated
      process (i.e. the redox pathway), and contribute to the initiation of osteolysis
      at the bone-implant interface.

PMID- 12527287
TI  - Interpolymer complexes of poly(acrylic acid) and chitosan: influence of the ionic
      hydrogel-forming medium.
AB  - Non-covalent polyionic complexes were developed for localized antibiotic delivery
      in the stomach. Freeze-dried interpolymer complexes based on polyacrylic acid
      (PAA) and chitosan (CS) were prepared in a wide range of copolymer compositions
      by dissolving both polymers in acidic conditions. The influence of hydrogel
      forming medium on the swelling and drug release was evaluated. The properties of
      these complexes were investigated by using scanning electron microscopy, dynamic
      swelling/eroding and release experiments in enzyme-free simulated gastric fluid
      (SGF). The electrostatic polymer/polymer interactions generate polyionic
      complexes with different porous structures. In a low pH environment, the
      separation of both polymer chains augmented as the amount of cationic and
      carboxilic groups increased within the network. However, the presence of higher
      amount of ions in the hydrogel-forming medium produced a network collapse,
      decreasing the maximum swelling ratio in SGF. PAA:CS:A (1:2.5:2)-1.75 M complexes
      released around 54% and 71% of the amoxicillin in 1 and 2 h, respectively, in
      acidic conditions. A faster drug release from this interpolymer complex was
      observed when the ionic strength of the hydrogel-forming medium increased.
      Complexes with a high amount of both polymer chains within the network,
      PAA:CS:A(2.5:5:2), showed a suitable amoxicillin release without being affected
      by an increased amount of ions in the hydrogel-forming medium. These freeze-dried
      interpolymer complexes could serve as potential candidates for amoxicillin
      delivery in an acidic enviroment.

PMID- 12527288
TI  - Evaluating the in vitro adhesive strength of biomaterials. Biosimulator for
      selective leak closure.
AB  - AIMS: Surgical measures always involve problems of hemostasis and tissue
      management. Tissue sealing can be carried out in this case, with knowledge of the
      adhesive strength of liquid and fleece-bound sealing being of great clinical
      relevance. By employing a leak closure model, it has been possible to perform in
      vitro standardized technological-biomechanical experiments on a biomembrane
      mounted in a pressure chamber (biosimulator). FINDINGS: Liquid sealing (fibrin
      gluing: 4.1 hPa, photopolymerisate: 82.9 hPa) offers minimal and maximal adhesive
      strengths. Fleece-bound sealing does not depend on the carrier material and is
      always more stabile than pure liquid sealing, whereby systems that must be coated
      "on the spot" (prepare-to-use: 22.3-25.3 hPa) exhibit significantly lower
      adhesive strength (p < 0.0001) than a biodegradable collagen system, which is
      ready-to-use thanks to its fibrinogen-based coating (TachoComb H).
      Practicability, effectiveness and efficiency are further advantages of ready-to
      use systems. CONCLUSIONS: The biosimulator, presented here, is flexible in terms
      of its application for tissue management and it enables reproducible, economic
      and ecological evaluation of repair systems, e.g. tissue sealings.

PMID- 12527289
TI  - Covalent bonding of lysine to EVAL membrane surface to improve survival of
      cultured cerebellar granule neurons.
AB  - Polylysine is a commonly used coating material in the preparation of neuronal
      cultures. In the present study, poly (ethylene-co-vinyl alcohol) (EVAL) membranes
      were modified by the covalent bonding of lysine via isocyanation of surface
      hydroxyl groups to improve cell behavior in cultured cerebellar granule neurons
      from 7-day-old Wistar rats. Cell survival and death ratio were assayed by MTT
      reduction activity and lactate dehydrogenase release, respectively. Cell
      morphology and neurite growth were observed by a scanning electron microscope. It
      was found that immobilizing lysine onto the EVAL membranes could improve neuronal
      MTT reduction activity and delay the death rate of neurons. In addition, neurons
      seeded on the lysine-immobilized EVAL membrane were able to regenerate with the
      formation of an extensive neuritic network, indicating that the surface
      modification on the EVAL membrane should be useful for culturing of neurons.
      Furthermore, the influence exerted by the modification of different amino acids
      (glycine, arginine and ornithine) onto the EVAL membranes on the neuronal
      behavior were investigated. We found that the effect of the terminal primary
      amine of the side chain of the basic amino acids on the neuronal behavior should
      be taken into account because the immobilized glycine molecules did not improve
      neuronal cultures. In order to interpret the phenomenon further, in the surface
      modification process, both the two amino groups of lysine were designed to react
      with the EVAL membrane surface to form a cyclic structure. On such a surface,
      neuronal MTT reduction activity was decreased and neuronal death was not delayed.
      The result shows that the lysine molecules immobilized on the EVAL membrane
      surface can mediate cellular response to promote neuronal cell survival and
      guidance of neuritic processes, indicating a delicate interaction of neuron with
      lysine molecules on the EVAL membrane surface.

PMID- 12527290
TI  - Novel collagen scaffolds with predefined internal morphology made by solid
      freeform fabrication.
AB  - Novel collagen scaffolds possessing predefined and reproducible internal channels
      with widths of 135 microm and greater have been produced. The process employed to
      make the collagen scaffold utilises a sacrificial mould, manufactured using solid
      freeform fabrication technology, and critical point drying technique. A computer
      aided design (CAD) file of the mould to be produced is created. This mould is
      manufactured using a phase change ink-jet printer. A dispersion of collagen is
      then cast into the mould and frozen. The mould is dissolved away with ethanol and
      the collagen scaffold is then critical point dried with liquid carbon dioxide.
      The effect of processing on the tertiary structure of collagen is assessed by
      monitoring the wavenumber of the N-H stretching vibration peak using Fourier
      transform infra-red spectroscopy and it is found that processing does not
      denature the collagen. Ultraviolet-visual spectroscopy was used to detect the
      presence of any contamination from the sacrificial mould on the collagen. The
      ability to use computer aided design and manufacture (CAD/CAM) provides a route
      to optimise scaffold designs using collagen in tissue engineering applications.

PMID- 12527291
TI  - Release of amoxicillin from polyionic complexes of chitosan and poly(acrylic
      acid). Study of polymer/polymer and polymer/drug interactions within the network
      structure.
AB  - Polyionic complexes of chitosan (CS) and poly(acrylic acid) (PAA) were prepared
      in a wide range of copolymer composition and with two kind of drugs. Release of
      amoxicillin trihydrate and amoxicillin sodium from these different complexes were
      studied. The swelling behavior of and solute transport in swellable hydrogels
      were investigated to check the effect of polymer/polymer and polymer/drugs
      interactions. The electrostatic polymer/polymer interactions take place between
      the cationic groups from CS and the anionic ones from PAA. The diffusion of
      amoxicillin trihydrate was controlled only by the swelling/eroding ratio of the
      polyionic complexes. The swelling degree of amoxicillin sodium hydrogels was more
      extensive when compared to the swelling degree of amoxicillin trihydrate
      formulations. It was concluded that the water uptake was mainly governed by the
      degree of ionization. Restriction of amoxicillin sodium diffusion could be
      achieved by polymer/ionized-drug interaction that retards the drug release.
      Freeze-dried polyionic complexes could serve as suitable candidates for
      amoxicillin site-specific delivery in the stomach.

PMID- 12527292
TI  - Adhesion of Pseudomonas aeruginosa strains to untreated and oxygen-plasma treated
      poly(vinyl chloride) (PVC) from endotracheal intubation devices.
AB  - Pseudomonas aeruginosa pneumonia is a life threatening complication in
      mechanically ventilated patients that requires the ability of the bacteria to
      adhere to, and colonize the endotracheal intubation device. New strategies to
      prevent or reduce these nosocomial infections are greatly needed. We report here
      the study of a set of P. aeruginosa clinical isolates, together with specific
      mutants, regarding their adhesion on native and chemically modified poly(vinyl
      chloride) (PVC) surfaces from endotracheal intubation devices. The adhesion of
      the different strains to untreated PVC varied widely, correlating with several
      physico-chemical characteristics known to influence the attachment of bacteria to
      inert surfaces. The adhesion patterns were compared to the calculations obtained
      with the DLVO theory of colloidal stability. These results illustrate the
      importance of testing different clinical isolates when investigating bacterial
      adhesion. Oxygen plasma treatment of the PVC pieces yielded a hydrophilic surface
      and reduced the number of adhering bacteria by as much as 70%. This reduction is
      however unlikely to be sufficient to prevent P. aeruginosa colonization of
      endotracheal intubation devices.

PMID- 12527293
TI  - Wear properties of Ti and Ti-6Al-7Nb castings for dental prostheses.
AB  - Titanium has been increasingly applied to dental prostheses because of its
      biocompatibility. However, application remains limited, due to the low strength
      and poor wear resistance of unalloyed titanium. The purpose of this study is to
      evaluate the wear resistance of high-strength Ti-6Al-7Nb alloy castings for
      dental application. Test specimens were cast from commercially pure titanium (CP
      Ti grades 2 and 3) and Ti-6Al-7Nb alloy ingots, and subjected to a wear test
      simulating the occlusal loading pattern. Wear resistance was evaluated by the
      weight loss during the test. Ti-6Al-7Nb alloy was found to exhibit lower weight
      loss than CP-Ti. Moreover, scanning electron microscopic (SEM) observation after
      the test revealed that the worn surface of Ti-6Al-7Nb alloy is much smoother than
      that of CP-Ti. These results indicate that Ti-6Al-7Nb alloy castings can be used
      to produce dental prostheses of improved wear resistance and mechanical strength.

PMID- 12527294
TI  - Analysis of regions within the bacteriophage T4 AsiA protein involved in its
      binding to the sigma70 subunit of E. coli RNA polymerase and its role as a
      transcriptional inhibitor and co-activator.
AB  - Bacteriophage T4 AsiA, a protein of 90 amino acid residues, binds to the
      sigma(70) subunit of Escherichia coli RNA polymerase and inhibits host or T4
      early transcription or, together with the T4 MotA protein, activates T4 middle
      transcription. To investigate which regions within AsiA are involved in forming a
      complex with sigma(70) and in providing transcriptional functions we generated
      random mutations throughout AsiA and targeted mutations within the C-terminal
      region. We tested mutant proteins for their ability to complement the growth of
      T4 asiA am phage under non-suppressing conditions, to inhibit E. coli growth, to
      interact with sigma(70) region 4 in a two-hybrid assay, to bind to sigma(70) in a
      native protein gel, and to inhibit or activate transcription in vitro using a T4
      middle promoter that is active with RNA polymerase alone, is inhibited by AsiA,
      and is activated by MotA/AsiA. We find that substitutions within the N-terminal
      half of AsiA, at amino acid residues V14, L18, and I40, rendered the protein
      defective for binding to sigma(70). These residues reside at the monomer-monomer
      interface in recent NMR structures of the AsiA dimer. In contrast, AsiA missing
      the C-terminal 44 amino acid residues interacted well with sigma(70) region 4 in
      the two-hybrid assay, and AsiA missing the C-terminal 17 amino acid residues
      (Delta74-90) bound to sigma(70) and was fully competent in standard in vitro
      transcription assays. However, the presence of the C-terminal region delayed
      formation of transcriptionally competent species when the AsiA/polymerase complex
      was pre-incubated with the promoter in the absence of MotA. Our results suggest
      that amino acid residues within the N-terminal half of AsiA are involved in
      forming or maintaining the AsiA/sigma(70) complex. The C-terminal region of AsiA,
      while not absolutely required for inhibition or co-activation, aids inhibition by
      slowing the formation of transcription complexes between a promoter and the
      AsiA/polymerase complex.

PMID- 12527295
TI  - The solution structure of the loop E region of the 5S rRNA from spinach
      chloroplasts.
AB  - A structure has been obtained for the loop E region of the 5S rRNA from Spinacia
      oleracia chloroplast ribosomes using residual dipolar coupling data as well as
      NOE, J coupling and chemical shift information. Even though the loop E sequence
      of this chloroplast 5S rRNA differs from that of Escherichia coli loop E at
      approximately 40% of its positions, its conformation is remarkably similar to
      that of E.coli loop E. Consistent with this conclusion, ribosomal protein L25
      from E.coli, which binds to the loop E region of both intact E.coli 5S rRNA and
      to oligonucleotides containing that sequence, also binds to the chloroplast
      derived oligonucleotide discussed here.

PMID- 12527296
TI  - Purification, characterization, and gene expression of all sigma factors of RNA
      polymerase in a cyanobacterium.
AB  - The expression of RNA polymerase (RNAP) sigma factor genes and proteins was
      characterized as a first step toward understanding their functions in a
      unicellular cyanobacterium Synechocystis sp. PCC 6803, which can perform
      photosynthesis. All nine sigma factors (group 1, SigA; group 2, SigB to SigE; and
      group 3, SigF to SigI) and each RNAP core subunit (RpoA, RpoB, RpoC1 and RpoC2)
      were overproduced and purified from Escherichia coli cells, then polyclonal
      antibodies were prepared. Western blot and primer extension analyses revealed
      that the intracellular levels of group 1 and 2 sigma factors ranged from 0.9 fmol
      to 9.3 fmol per microgram of the total protein under conditions of steady-state
      growth, and that growth phase-dependent or constitutive transcripts were
      observed. Interestingly, no group 3 sigma factor proteins were detected under
      normal physiological conditions whereas their transcripts were robust, implying a
      possible regulation of translational attenuation and/or protein instability.
      Phylogenetic analysis also revealed that group 3 sigma factor homologues of
      cyanobacteria are conserved with evolutionary or functionary divergence among
      them. In vitro and in vivo results indicated significant evidence of high-light
      responsive SigD expression and its promoter recognition of the photosynthesis
      gene, psbA. On the other hand, autoregulated sigB transcription, a dramatically
      increased SigB expression upon the exposure of cells to heat-shock, and specific
      promoter recognition by SigB with redundancy of other sigma factors on the heat
      shock hspA promoter were observed. These findings clearly indicated that SigB is
      a heat-shock responsive sigma factor. The unique promoter architecture and
      expression of the relevant sigma factor gene are also discussed herein.

PMID- 12527297
TI  - Nucleosome positioning signals in the DNA sequence of the human and mouse H19
      imprinting control regions.
AB  - We have investigated the sequences of the mouse and human H19 imprinting control
      regions (ICRs) to see whether they contain nucleosome positioning information
      pertinent to their function as a methylation-regulated chromatin boundary.
      Positioning signals were identified by an in vitro approach that employs
      reconstituted chromatin to comprehensively describe the contribution of the DNA
      to the most basic, underlying level of chromatin structure. Signals in the DNA
      sequence of both ICRs directed nucleosomes to flank and encompass the short
      conserved sequences that constitute the binding sites for the zinc finger protein
      CTCF, an essential mediator of insulator activity. The repeat structure of the
      human ICR presented a conserved array of strong positioning signals that would
      preferentially flank these CTCF binding sites with positioned nucleosomes, a
      chromatin structure that would tend to maintain their accessibility. Conversely,
      all four CTCF binding sites in the mouse sequence were located close to the
      centre of positioning signals that were stronger than those in their flanks;
      these binding sites might therefore be expected to be more readily incorporated
      into positioned nucleosomes. We found that CpG methylation did not effect
      widespread repositioning of nucleosomes on either ICR, indicating that allelic
      methylation patterns were unlikely to establish allele-specific chromatin
      structures for H19 by operating directly upon the underlying DNA-histone
      interactions; instead, epigenetic modulation of ICR chromatin structure is likely
      to be mediated principally at higher levels of control. DNA methylation did,
      however, both promote and inhibit nucleosome positioning at several sites in both
      ICRs and substantially negated one of the strongest nucleosome positioning
      signals in the human sequence, observations that underline the fact that this
      epigenetic modification can, nevertheless, directly and decisively modulate core
      histone-DNA interactions within the nucleosome.

PMID- 12527298
TI  - Self-association equilibria of Escherichia coli UvrD helicase studied by
      analytical ultracentrifugation.
AB  - The Escherichia coli UvrD protein (helicase II) is an SF1 superfamily helicase
      required for methyl-directed mismatch repair and nucleotide excision repair of
      DNA. We have characterized quantitatively the self-assembly equilibria of the
      UvrD protein as a function of [NaCl], [glycerol], and temperature (5-35 degrees
      C; pH 8.3) using analytical sedimentation velocity and equilibrium techniques,
      and find that UvrD self-associates into dimeric and tetrameric species over a
      range of solution conditions (t</=25 degrees C). Increasing [NaCl] from 20mM to
      200 mM decreases the dimerization equilibrium constant (L(20)) from 2.33(+/-0.30)
      microM(-1) to 0.297(+/-0.006) microM(-1) (pH 8.3, 20% (v/v) glycerol, 25 degrees
      C). The overall tetramerization equilibrium constant (L(40)) is 5.11(+/-0.80)
      microM(-3) at 20mM NaCl, but decreases so that it is not measurable at 200 mM
      NaCl. At 500 mM NaCl, only UvrD monomers are detectable. Increasing [glycerol]
      over the range from 20% to 40% (v/v) decreases both L(20) and L(40). We find no
      evidence for hexamer formation, although a species consistent in size with an
      octamer is detected at 35 degrees C. Inclusion of either ADP or ATPgammaS does
      not affect either L(20) or L(40) significantly, and does not induce the formation
      of additional assembly states. We also investigated the stoichiometry of UvrD
      binding to a 3'-(dT)(20)-18 bp DNA substrate by sedimentation equilibrium. At
      saturating concentrations of UvrD, three UvrD monomers can bind to the DNA
      substrate, although only two UvrD monomers are required to form a processive
      helicase complex. When the total DNA substrate concentration is about twofold
      greater than the total UvrD concentration, the vast majority of the DNA is bound
      by a single UvrD monomer.

PMID- 12527300
TI  - Coupling of protein assembly and DNA binding: biotin repressor dimerization
      precedes biotin operator binding.
AB  - The kinetics of coupling of protein dimerization and DNA binding have been
      investigated in the biotin repressor system. Two repressor monomers bind to the
      40 base-pair biotin operator sequence. In previous analyses of equilibrium
      binding data the weak dimerization of the repressor has justified using a model
      in which two protein monomers bind cooperatively to the operator site. Here,
      rapid kinetic methods have been used to directly determine the binding mechanism.
      Results of rapid-mixing DNaseI footprinting measurements of association of the
      repressor with operator indicate that the binding process involves at least two
      steps. Results of measurements of the unimolecular dissociation of the complex
      reveal a half-life of approximately 400 seconds. Analysis of the data using a
      combination of simulation and global non-linear least-squares analysis provides
      support for a binding model in which a preformed repressor dimer associates with
      the biotin operator. This kinetic model is consistent with the previously
      proposed model for regulation of the functional switch in the repressor from
      enzyme to site-specific DNA-binding protein.

PMID- 12527299
TI  - A Dimer of Escherichia coli UvrD is the active form of the helicase in vitro.
AB  - The Escherichia coli UvrD protein is a 3' to 5' SF1 DNA helicase involved in
      methyl-directed mismatch repair and nucleotide excision repair of DNA. We have
      characterized in vitro UvrD-catalyzed unwinding of a series of 18 bp duplex DNA
      substrates with 3' single-stranded DNA (ssDNA) tails ranging in length from two
      to 40 nt. Single turnover DNA-unwinding experiments were performed using chemical
      quenched flow methods, as a function of both [UvrD] and [DNA] under conditions
      such that UvrD-DNA binding is stoichiometric. Although a single UvrD monomer
      binds tightly to the single-stranded/double-stranded DNA (dsDNA) junction if the
      3' ssDNA tail is at least four nt, no unwinding was observed for DNA substrates
      with tail-lengths </=8 nt, even at high [UvrD]/[DNA] ratios. Unwinding is
      observed for DNA substrates with 3' ssDNA tail lengths >/=12 nt, and the
      unwinding amplitude displays a sigmoidal dependence on [UvrD(tot)]/[DNA(tot)].
      Quantitative analysis of these data indicates that a single UvrD monomer bound at
      the ssDNA/dsDNA junction of any DNA substrate, independent of 3' ssDNA tail
      length, is not competent to fully unwind even a short 18 bp duplex DNA, and that
      two UvrD monomers must bind the DNA substrate in order to form a complex that is
      able to unwind short DNA substrates in vitro. Other proteins, including a mutant
      UvrD with no ATPase activity as well as a monomer of the structurally homologous
      E.coli Rep helicase, cannot substitute for the second UvrD monomer, suggesting a
      specific interaction between two UvrD monomers and that both must be able to
      hydrolyze ATP. Initiation of DNA unwinding in vitro appears to require a dimeric
      UvrD complex in which one subunit is bound to the ssDNA/dsDNA junction, while the
      second subunit is bound to the 3' ssDNA tail.

PMID- 12527301
TI  - Polycystin-2 associates with tropomyosin-1, an actin microfilament component.
AB  - Polycystin-2 (PC2) is the product of the second cloned gene (PKD2) responsible
      for autosomal dominant polycystic kidney disease and has recently been shown to
      be a calcium-permeable cation channel. PC2 has been shown to connect indirectly
      with the actin microfilament. Here, we report a direct association between PC2
      and the actin microfilament. Using a yeast two-hybrid screen, we identified a
      specific interaction between the PC2 cytoplasmic C-terminal domain and
      tropomyosin-1 (TM-1), a component of the actin microfilament complex.
      Tropomyosins constitute a protein family of more than 20 isoforms arising mainly
      from alternative splicing and are present in muscle as well as non-muscle cells.
      We identified a new TM-1 splicing isoform in kidney and heart (TM-1a) that
      differs from TM-1 in the C terminus and interacted with PC2. In vitro biochemical
      methods, including GST pull-down, blot overlay and microtiter binding assays,
      confirmed the interaction between PC2 and the two TM-1 isoforms. Further
      experiments targeted the interacting domains to G821-R878 of PC2 and A152-E196, a
      common segment of TM-1 and TM-1a. Indirect double immunofluorescence experiments
      showed partial co-localization of PC2 and TM-1 in transfected mouse fibroblast
      NIH 3T3 cells. Co-immunoprecipitation (co-IP) studies using 3T3 cells and Xenopus
      oocytes co-expressing PC2 and TM-1 (or TM-1a) revealed in vivo association
      between the protein pairs. Furthermore, the in vivo interaction between the
      endogenous PC2 and TM-1 was demonstrated also by reciprocal co-IP using native
      human embryonic kidney cells and human adult kidney. Considering previous reports
      that TM-1 acts as a suppressor of neoplastic growth of transformed cells, it is
      possible that TM-1 contributes to cyst formation/growth when the anchorage of PC2
      to the actin microfilament via TM-1 is altered.

PMID- 12527302
TI  - Reconstructing the binding site of factor Xa in trypsin reveals ligand-induced
      structural plasticity.
AB  - In order to investigate issues of selectivity and specificity in protein-ligand
      interactions, we have undertaken the reconstruction of the binding pocket of
      human factor Xa in the structurally related rat trypsin by site-directed
      mutagenesis. Three sequential regions (the "99"-, the "175"- and the "190"-
      loops) were selected as representing the major structural differences between the
      ligand binding sites of the two enzymes. Wild-type rat trypsin and variants X99rT
      and X(99/175/190)rT were expressed in yeast, and analysed for their interaction
      with factor Xa and trypsin inhibitors. For most of the inhibitors studied,
      progressive loop replacement at the trypsin surface resulted in inhibitory
      profiles akin to factor Xa. Crystals of the variants were obtained in the
      presence of benzamidine (3), and could be soaked with the highly specific factor
      Xa inhibitor (1). Binding of the latter to X99rT results in a series of
      structural adaptations to the ligand, including the establishment of an "aromatic
      box" characteristic of factor Xa. In X(99/175/190)rT, introduction of the 175
      loop results in a surprising re-orientation of the "intermediate helix",
      otherwise common to trypsin and factor Xa. The re-orientation is accompanied by
      an isomerisation of the Cys168-Cys182 disulphide bond, and burial of the critical
      Phe174 side-chain. In the presence of (1), a major re-organisation of the binding
      site takes place to yield a geometry identical to that of factor Xa. In all,
      binding of (1) to trypsin and its variants results in significant structural
      rearrangements, inducing a binding surface strongly reminiscent of factor Xa,
      against which the inhibitor was optimised. The structural data reveal a
      plasticity of the intermediate helix, which has been implicated in the functional
      cofactor dependency of many trypsin-like serine proteinases. This approach of
      grafting loops onto scaffolds of known related structures may serve to bridge the
      gap between structural genomics and drug design.

PMID- 12527303
TI  - Structural analysis of human IgG-Fc glycoforms reveals a correlation between
      glycosylation and structural integrity.
AB  - Antibodies may be viewed as adaptor molecules that provide a link between humoral
      and cellular defence mechanisms. Thus, when antigen-specific IgG antibodies form
      antigen/antibody immune complexes the effectively aggregated IgG can activate a
      wide range of effector systems. Multiple effector mechanisms result from cellular
      activation mediated through a family of IgG-Fc receptors differentially expressed
      on leucocytes. It is established that glycosylation of IgG-Fc is essential for
      recognition and activation of these ligands. IgG antibodies predominate in human
      serum and most therapeutic antibodies are of the IgG class. The IgG-Fc is a
      homodimer of N-linked glycopeptide chains comprised of two immunoglobulin domains
      (Cgamma2, Cgamma3) that dimerise via inter-heavy chain disulphide bridges at the
      N-terminal region and non-covalent interactions between the C-terminal Cgamma3
      domains. The overall shape of the IgG-Fc is similar to that of a "horseshoe" with
      a majority of the internal space filled by the oligosaccharide chains, only
      attached through asparagine residues 297.To investigate the influence of
      individual sugar (monosaccharide) residues of the oligosaccharide on the
      structure and function of IgG-Fc we have compared the structure of "wild-type"
      glycosylated IgG1-Fc with that of four glycoforms bearing consecutively truncated
      oligosaccharides. Removal of terminal N-acetylglucosamine as well as mannose
      sugar residues resulted in the largest conformational changes in both the
      oligosaccharide and in the polypeptide loop containing the N-glycosylation site.
      The observed conformational changes in the Cgamma2 domain affect the interface
      between IgG-Fc fragments and FcgammaRs. Furthermore, we observed that the removal
      of sugar residues permits the mutual approach of Cgamma2 domains resulting in the
      generation of a "closed" conformation; in contrast to the "open" conformation
      which was observed for the fully galactosylated IgG-Fc, which may be optimal for
      FcgammaR binding. These data provide a structural rationale for the previously
      observed modulation of effector activities reported for this series of proteins.

PMID- 12527304
TI  - Structural characterisation and functional significance of transient protein
      protein interactions.
AB  - Protein-protein complexes that dissociate and associate readily, often depending
      on the physiological condition or environment, play an important role in many
      biological processes. In order to characterise these "transient" protein-protein
      interactions, two sets of complexes were collected and analysed. The first set
      consists of 16 experimentally validated "weak" transient homodimers, which are
      known to exist as monomers and dimers at physiological concentration, with
      dissociation constants in the micromolar range. A set of 23 functionally
      validated transient (i.e. intracellular signalling) heterodimers comprise the
      second set. This set includes complexes that are more stable, with nanomolar
      binding affinities, and require a molecular trigger to form and break the
      interaction. In comparison to more stable homodimeric complexes, the weak
      homodimers demonstrate smaller contact areas between protomers and the interfaces
      are more planar and polar on average. The physicochemical and geometrical
      properties of these weak homodimers more closely resemble those of non-obligate
      hetero-oligomeric complexes, whose components can exist either as monomers or as
      complexes in vivo. In contrast to the weak transient dimers, "strong" transient
      dimers often undergo large conformational changes upon association/dissociation
      and are characterised with larger, less planar and sometimes more hydrophobic
      interfaces. From sequence alignments we find that the interface residues of the
      weak transient homodimers are generally more conserved than surface residues,
      consistent with being constrained to maintain the protein-protein interaction
      during evolution. Protein families that include members with different oligomeric
      states or structures are identified, and found to exhibit a lower sequence
      conservation at the interface. The results are discussed in terms of the
      physiological function and evolution of protein-protein interactions.

PMID- 12527305
TI  - Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A
      reveals the mechanism for beta-lactam acetylation.
AB  - Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing
      pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here,
      we report the crystal structure of TTR complexed with its natural cofactor,
      acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a
      characteristic "V" shape for substrate binding and contains the four motifs
      conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also
      includes the histone acetyltransferases (HATs). A single-step mechanism is
      proposed to explain the function of three conserved residues, Glu92, Asp130 and
      Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report
      that TTR possesses HAT activity and suggest an evolutionary relationship between
      TTR and other GNAT members.

PMID- 12527306
TI  - Structure based hyperthermostability of archaeal histone HPhA from Pyrococcus
      horikoshii.
AB  - The histone protein HPhA from the hyperthermophilic archaeon Pyrococcus
      horikoshii, shows hyperthermostability, as required for optimal growth of the
      organism at 95 degrees C. The structure of recombinant P.horikoshii HPhA has been
      determined to 2.3A resolution by molecular replacement, and refined to R(work)
      and R(free) values of 20.7% and 27.3%, respectively. The HPhA monomer structure
      is characterized by the histone fold and assembles into a homodimer like other
      archaeal histones. There are four anions found in the dimer structure, giving
      rise to clues as to where DNA might bind. A detailed comparison of four known
      structures of archaeal histones, which evolve and exist under different
      temperatures, shows that the thermophilic archaeal histone HPhA has a larger
      hydrophobic contact area, an increased number of hydrogen bonds and a reduced
      solvent-accessible area. We also observe a unique network of tyrosine residues
      located at the crossover point of the two HPhA monomers, which locks them
      together and stabilizes the dimer. These factors together account for the
      increased thermal stability.

PMID- 12527307
TI  - Modelling zinc-binding proteins with GADGET: genetic algorithm and distance
      geometry for exploring topology.
AB  - A novel combination of optimization methods (Genetic Algorithm with Distance
      Geometry) has been developed and shown to find near-optimal solutions to a set of
      imposed structural constraints. With this modelling tool (GADGET), the fold-space
      of a variety of small zinc-binding proteins was investigated under the
      constraints required to form a zinc-binding site (or pair of sites). Analysis of
      the results concentrated on the ring-finger domain as the "classic" zinc-finger
      domains were too constrained to provide much topological variety, whilst the
      TFIIH domain (which has large unstructured loops) did not behave well. The
      intermediate ring-finger domain, however, was found to adopt a variety of
      different folds, many of which had near-optimal scores under the fitness function
      employed in GADGET (forming good secondary structures and zinc-coordination).
      Although the native fold was dominant amongst the solutions, the discovery of
      good alternate folds shows that even the eight residues constrained to form two
      zinc-binding sites was not sufficient to uniquely determine the native fold.
      Despite this, the fold-space of 48 theoretically possible folds was greatly
      reduced with just six topologies found in significant numbers.

PMID- 12527308
TI  - Probing the role of a mobile loop in substrate binding and enzyme activity of
      human salivary amylase.
AB  - Mammalian amylases harbor a flexible, glycine-rich loop 304GHGAGGA(310), which
      becomes ordered upon oligosaccharide binding and moves in toward the substrate.
      In order to probe the role of this loop in catalysis, a deletion mutant lacking
      residues 306-310 (Delta306) was generated. Kinetic studies showed that Delta306
      exhibited: (1) a reduction (>200-fold) in the specific activity using starch as a
      substrate; (2) a reduction in k(cat) for maltopentaose and maltoheptaose as
      substrates; and (3) a twofold increase in K(m) (maltopentaose as substrate)
      compared to the wild-type (rHSAmy). More cleavage sites were observed for the
      mutant than for rHSAmy, suggesting that the mutant exhibits additional productive
      binding modes. Further insight into its role is obtained from the crystal
      structures of the two enzymes soaked with acarbose, a transition-state analog.
      Both enzymes modify acarbose upon binding through hydrolysis, condensation or
      transglycosylation reactions. Electron density corresponding to six and seven
      fully occupied subsites in the active site of rHSAmy and Delta306, respectively,
      were observed. Comparison of the crystal structures showed that: (1) the
      hydrophobic cover provided by the mobile loop for the subsites at the reducing
      end of the rHSAmy complex is notably absent in the mutant; (2) minimal changes in
      the protein-ligand interactions around subsites S1 and S1', where the cleavage
      would occur; (3) a well-positioned water molecule in the mutant provides a
      hydrogen bond interaction similar to that provided by the His305 in rHSAmy
      complex; (4) the active site-bound oligosaccharides exhibit minimal
      conformational differences between the two enzymes. Collectively, while the
      kinetic data suggest that the mobile loop may be involved in assisting the
      catalysis during the transition state, crystallographic data suggest that the
      loop may play a role in the release of the product(s) from the active site.

PMID- 12527309
TI  - Charge-charge interactions are key determinants of the pK values of ionizable
      groups in ribonuclease Sa (pI=3.5) and a basic variant (pI=10.2).
AB  - The pK values of the titratable groups in ribonuclease Sa (RNase Sa) (pI=3.5),
      and a charge-reversed variant with five carboxyl to lysine substitutions, 5K
      RNase Sa (pI=10.2), have been determined by NMR at 20 degrees C in 0.1M NaCl. In
      RNase Sa, 18 pK values and in 5K, 11 pK values were measured. The carboxyl group
      of Asp33, which is buried and forms three intramolecular hydrogen bonds in RNase
      Sa, has the lowest pK (2.4), whereas Asp79, which is also buried but does not
      form hydrogen bonds, has the most elevated pK (7.4). These results highlight the
      importance of desolvation and charge-dipole interactions in perturbing pK values
      of buried groups. Alkaline titration revealed that the terminal amine of RNase Sa
      and all eight tyrosine residues have significantly increased pK values relative
      to model compounds.A primary objective in this study was to investigate the
      influence of charge-charge interactions on the pK values by comparing results
      from RNase Sa with those from the 5K variant. The solution structures of the two
      proteins are very similar as revealed by NMR and other spectroscopic data, with
      only small changes at the N terminus and in the alpha-helix. Consequently, the
      ionizable groups will have similar environments in the two variants and
      desolvation and charge-dipole interactions will have comparable effects on the pK
      values of both. Their pK differences, therefore, are expected to be chiefly due
      to the different charge-charge interactions. As anticipated from its higher net
      charge, all measured pK values in 5K RNase are lowered relative to wild-type
      RNase Sa, with the largest decrease being 2.2 pH units for Glu14. The pK
      differences (pK(Sa)-pK(5K)) calculated using a simple model based on Coulomb's
      Law and a dielectric constant of 45 agree well with the experimental values. This
      demonstrates that the pK differences between wild-type and 5K RNase Sa are mainly
      due to changes in the electrostatic interactions between the ionizable groups. pK
      values calculated using Coulomb's Law also showed a good correlation (R=0.83)
      with experimental values. The more complex model based on a finite-difference
      solution to the Poisson-Boltzmann equation, which considers desolvation and
      charge-dipole interactions in addition to charge-charge interactions, was also
      used to calculate pK values. Surprisingly, these values are more poorly
      correlated (R=0.65) with the values from experiment. Taken together, the results
      are evidence that charge-charge interactions are the chief perturbant of the pK
      values of ionizable groups on the protein surface, which is where the majority of
      the ionizable groups are positioned in proteins.

PMID- 12527310
TI  - pK values of histidine residues in ribonuclease Sa: effect of salt and net
      charge.
AB  - The primary goal of this study was to gain a better understanding of the effect
      of environment and ionic strength on the pK values of histidine residues in
      proteins. The salt-dependence of pK values for two histidine residues in
      ribonuclease Sa (RNase Sa) (pI=3.5) and a variant in which five acidic amino
      acids have been changed to lysine (5K) (pI=10.2) was measured and compared to pK
      values of model histidine-containing peptides. The pK of His53 is elevated by two
      pH units (pK=8.61) in RNase Sa and by nearly one pH unit (pK=7.39) in 5K at low
      salt relative to the pK of histidine in the model peptides (pK=6.6). The pK for
      His53 remains elevated in 1.5M NaCl (pK=7.89). The elevated pK for His53 is a
      result of screenable electrostatic interactions, particularly with Glu74, and a
      non-screenable hydrogen bond interaction with water. The pK of His85 in RNase Sa
      and 5K is slightly below the model pK at low salt and merges with this value at
      1.5M NaCl. The pK of His85 reflects mainly effects of long-range Coulombic
      interactions that are screenable by salt. The tautomeric states of the neutral
      histidine residues are changed by charge reversal. The histidine pK values in
      RNase Sa are always higher than the pK values in the 5K variant. These results
      emphasize that the net charge of the protein influences the pK values of the
      histidine residues. Structure-based pK calculations capture the salt-dependence
      relatively well but are unable to predict absolute histidine pK values.

PMID- 12527312
TI  - Factors influencing the features of postherpetic neuralgia and outcome when
      treated with tricyclics.
AB  - This paper retrospectively reviews features of postherpetic neuralgia (PHN) in up
      to 279 personal patients in relation to treatment outcome when treated with
      tricyclic antidepressants (TCAs). Factors affecting characteristics of PHN: (i)
      Patients with allodynia (89%) and/or burning pain (56%) have a much higher visual
      analogue pain intensity score than those without; (ii) Acyclovir (ACV) given for
      acute shingles (HZ) does not reduce the incidence of subsequent PHN, but reduces
      the pain intensity in PHN patients with allodynia; (iii) ACV given for acute HZ
      reduces the incidence of burning pain in subsequent PHN, but not of allodynia;
      (iv) ACV given for acute HZ reduces the incidence of clinically detectable
      sensory deficit in subsequent PHN. Factors affecting outcome of TCA-treated PHN:
      (i) The point in time at which TCA treatment is commenced is by far the most
      critical factor: started between 3 and 12 months after acute HZ onset, more than
      two-thirds obtain pain relief (NNT=1.8); between 13 and 24 months, two-fifths
      (41%) (NNT=3.6); and more than two years, one-third (NNT=8.3). Background and
      paroxysmal pain disappear earlier and are more susceptible of relief than
      allodynia. (ii) Twice as many (86%) of PHN patients without allodynia obtain pain
      relief with TCA treatment than those with (42%); (iii) the use of ACV for acute
      HZ more than halves the time-to-relief of PHN patients by TCAs; (iv) PHN patients
      with burning pain are significantly less likely to obtain pain relief with TCAs
      than those without (p<0.0001).

PMID- 12527313
TI  - Disuse and deconditioning in chronic low back pain: concepts and hypotheses on
      contributing mechanisms.
AB  - For years enhancement of a patient's level of physical fitness has been an
      important goal in rehabilitation treatment in chronic low back pain (CLBP), based
      on the hypothesis that physical deconditioning contributes to the chronicity of
      low back pain. However, whether this hypothesis in CLBP holds is not clear. In
      this paper, possible mechanisms that contribute to the development of physical
      deconditioning in CLBP, such as avoidance behaviour and suppressive behaviour,
      are discussed. The presence of both deconditioning-related physiological changes,
      such as muscle atrophy, changes in metabolism, osteoporosis and obesity as well
      as deconditioning related functional changes, such as a decrease in
      cardiovascular capacity, a decrease in muscle strength and impaired motor control
      in patients with CLBP are discussed. Results of studies on the level of physical
      activities in daily life (PAL) and the level of physical fitness in patients with
      CLBP compared to healthy controls were reviewed. In studies on PAL results that
      were either lower or comparable to healthy subjects were found. The presence of
      disuse (i.e., a decrease in the level of physical activities in daily life) in
      patients with CLBP was not confirmed. The inconclusive findings in the papers
      reviewed may partly be explained by different measurement methods used in
      research on PAL in chronic pain. The level of physical fitness of CLBP patients
      also appeared to be lower or comparable to the fitness level of healthy persons.
      A discriminating factor between fit and unfit patients with back pain may be the
      fact that fit persons more frequently are still employed, and as such may be
      involved more in physical activity. Lastly some suggestions are made for further
      research in the field of disuse and deconditioning in CLBP.

PMID- 12527314
TI  - Painful and non-painful neuropathy in HIV-infected patients: an analysis of
      somatosensory nerve function.
AB  - Fifteen to 50% of AIDS-patients suffer from distal predominantly sensory
      neuropathy (DSP), which is commonly associated with painful symptoms. In the
      present study, we have focused on the function of fine calibre nerve channels, in
      36 consecutive HIV-1-infected patients with painful (PPN) (n=20; 54%) and non
      painful (PN) (n=16) sensory neuropathy, assessed by clinical, quantitative
      thermal testing (QTT) (31/36), and peripheral nerve conduction examination
      (32/36). Control QTT data were obtained from 49 healthy subjects with a
      corresponding age- and sex distribution. Demographics, antiviral treatment,
      immunological status, and nerve conduction examination did not differ between
      patients with and without painful symptoms. Hypoaesthesia to warmth, cold, and
      heat pain was observed in both neuropathy groups when compared to healthy
      controls. However, the perception threshold to warmth was more often impaired
      (p<0.01) and the level of impairment was more pronounced (p<0.001) in patients
      with painful neuropathy. Furthermore, increased pain sensitivity to cold was
      found only in patients with painful symptoms (p<0.05). An abnormal outcome of any
      QTT parameter was found in all patients with pain, but only among 62% of patients
      without pain, p<0.01, and the cumulative frequency of abnormalities in any of the
      four thermal percepts (warmth, cold, heat pain, and cold pain) was higher in
      patients with painful symptoms, p<0.0001. This study demonstrates a more
      pronounced impairment of C-fibre-mediated innocuous warm perception in patients
      with painful neuropathy, which in the setting of impaired or absent heat pain
      perception suggests a more generalised loss of function in somatosensory C-fibre
      channels.

PMID- 12527315
TI  - Implicit attitude towards pictures of back-stressing activities in pain-free
      subjects and patients with low back pain: an affective priming study.
AB  - In this paper, it is investigated whether an implicit evaluative-negative
      attitude towards back-stressing activities exists in pain-free subjects and in
      chronic low back pain patients. Using an affective priming task, it was
      investigated whether pictures of threatening back-stressing movements (primes)
      facilitate (respectively, slow down) the categorisation of subsequent evaluative
      negative (evaluative-positive) words (targets). In study 1 using 20 pain-free
      subjects, the affective priming effect indicated evidence for an implicit
      negative attitude towards pictures of back-stressing activities. In study 2 using
      30 low back pain patients, a reverse priming effect was found. In line with
      previous research, it is argued that this reverse priming effect is owing to the
      evaluative extremity of the primes: patients recognize the possibility that
      extreme primes will interfere with the categorisation of the targets and
      overcompensate for this possible effect. The implications for the prevention of
      negative attitudes towards back-stressing activities in non-clinical and clinical
      samples are discussed.

PMID- 12527316
TI  - The treatment of complex regional pain syndrome (CRPS) involving upper extremity
      with continuous sensory analgesia.
AB  - Continuous sensory analgesia of brachial plexus (CSA BP) was only occasionally
      reported to have been used in the treatment of CRPS. In the past four years, we
      have treated 21 patients with a working diagnosis of CRPS. The treatment was
      instituted one to six months after inciting injury. All patients were admitted to
      hospital. In the first two days, the therapy consisted of elevation, cryotherapy,
      and active exercises. Five patients responded well to this initial physiotherapy
      (5/21). In 16 cases, no evident improvement was observed and CSA BP was
      introduced. At follow-up (3-36 months), the results were: 13/16 (81%) had at
      least good results (excellent 2, good without any sequelae 5, good with sequelae
      of initial injury 6, and poor 3). The results were judged as follows: excellent
      (completely normal hand); good (only temporary pain up to 2 on a 0-10 numeric
      rating scale; no signs of dysfunction of sympathetic nervous system; ROM of wrist
      over 50% of normal hand; ROM of fingers excellent or good; and the strength of
      hand grasp and key pinch over 50% of normal hand measured with dynamometer) and
      if any of the former criteria was missing, the result was defined as poor.

PMID- 12527317
TI  - Comparison of the effect of video glasses and nitrous oxide analgesia on the
      perceived intensity of pain and unpleasantness evoked by dental scaling.
AB  - The aim of this study was to evaluate whether distraction induced by video
      glasses had an effect on the perceived intensity of pain and unpleasantness
      during dental scaling compared with the effect of nitrous oxide (N(2)O)
      analgesia. The pain stimulus was dental scaling (removal of dental calculus) with
      an ultrasonic scaler. As a standardised, non-dental painful stimulus, Von Frey
      filaments were used. A total of 26 patients with superficial chronic
      periodontitis were enrolled in this randomised, controlled clinical study. The
      effect of video glasses was compared with N(2)O in one session and the effect of
      video glasses versus a control situation in another. The patients rated the
      intensity of pain and unpleasantness evoked by dental scaling and Von Frey
      filament stimulation on 100-mm visual analogue scales (VAS). For dental scaling,
      there was no effect of video glasses on the perceived pain (p=0.85) or
      unpleasantness (p=0.73) nor of N(2)O (p=0.69 and p=0.51, respectively) compared
      with the control situation. Similarly, no significant difference was found
      between VAS scores in the video glasses and N(2)O session (p=0.48, p=0.58). A
      significant effect of video glasses and N(2)O(p<0.008) was found on the perceived
      pain intensity produced by Von Frey filament stimulation compared with the
      control situation, but no significant difference was seen between these methods
      (p=0.07). Post-treatment interviews of the patients revealed that 81% of the
      patients in the video and 65% in the N(2)O session stated that the method had
      some beneficial effect on their overall experience of the treatment situation. In
      conclusion, administration of video glasses or N(2)O did not affect the perceived
      intensity of pain and unpleasantness evoked by dental scaling.

PMID- 12527318
TI  - Suppression of motor evoked potentials in a hand muscle following prolonged
      painful stimulation.
AB  - Earlier investigations have shown that stimulation of peripheral afferent nerves
      induces prolonged changes in the excitability of the human motor cortex. The
      present study compared the effect of experimental pain and non-painful
      conditioning stimulation on motor evoked potentials (MEPs) elicited by
      transcranial magnetic stimulation (TMS) in the relaxed first dorsal interosseous
      (FDI) and flexor carpi ulnaris (FCU) muscles. The MEPs were measured in 10
      healthy subjects, and stimulus-response curves were generated before and after
      each of four stimulation paradigms conducted in random order on separate
      occasions: (a) control; (b) "dual stimulation" consisting of electrical
      stimulation of the FDI motor point paired with TMS; (c) painful infusion of
      hypertonic saline in the FDI muscle; and (d) pain combined with dual stimulation.
      There were no significant changes in FDI MEPs following the control paradigm, and
      dual stimulation induced an increase in the FDI MEPs only inconsistently. In
      contrast, the painful stimulation and the combined pain and dual stimulation
      paradigms were followed by significant suppression of the FDI MEPs at higher
      stimulus intensities. No changes were observed in the FCU MEPs following the four
      paradigms. In two additional subjects, the responses evoked in FDI by direct
      stimulation of the descending corticospinal tracts were significantly depressed
      following painful stimulation of the FDI, although the ulnar-evoked M-waves
      remained constant. It is concluded that muscle pain is followed by a period with
      profound depression of MEPs amplitudes in the resting muscle, but that these
      changes are at least in part due to a lasting depression of the excitability of
      the motoneurones in the spinal cord. Hence, painful stimulation differs from non
      painful, repetitive stimulation, which facilitates the corticomotor pathway.

PMID- 12527319
TI  - The significance of A-delta and C fibres for the perception of synthetic heat.
AB  - Synthetic heat is a perception of strong, but not painful, heat arising when skin
      is stimulated by an alternating pattern of adjacent cold and warmth. This study
      examines the contribution of different classes of nerve fibres to this
      perception. In 40 subjects changes in synthetic heat and thermal perceptions were
      studied during a 30-min ischaemic nerve block in one reaction time, and one
      threshold determination task. Synthetic heat stimuli were described as hot or
      warm, but not as painful, and were preceded by a transient cold. Reaction times
      for synthetic heat stimuli did not differ from those for cold stimuli. Thresholds
      for synthetic heat and thermal stimuli were similar. During A fibre nerve block
      the perception of synthetic heat lost the cold component whereas the frequency of
      hot and warm descriptors did not change. The perception of cold stimuli changed,
      such that pure cold was replaced by dysaesthetic descriptors. Reaction times and
      thresholds for thermal and synthetic heat stimuli increased equally during the
      nerve block. It is concluded that the perception of synthetic heat most likely
      arises from the fusion of signals dependent on unmyelinated low threshold cold
      and warm receptors. It is not dependent on A-delta cold fibres, and a
      contribution of nociceptors is quite unlikely. The possibility of a psychological
      contribution at the perceptual level is discussed.

PMID- 12527320
TI  - Experimental muscle pain provokes long-lasting alterations of thermal sensitivity
      in the referred pain area.
AB  - This study explores thermal sensitivity and thermal nociception for signs of
      central sensitization in the area of referred muscle pain. Two groups of 24
      healthy subjects (ss) each, and with mean ages of, respectively, 27 and 55 years,
      were first trained in quantitative sensory testing and pain rating. Then, in a
      second session, referred pain was evoked by injection of 6% hypertonic saline
      into the infraspinatus muscle. Cold and warm thresholds, synthetic heat threshold
      (SHT--evoked by an alternating pattern of adjacent cold and warmth), and thermal
      pain thresholds were measured within the referred pain area at a rate of 1/20 min
      for 60-120 min. All ss of both groups experienced referred pain mostly in the
      upper arm and of medium intensity. Pain lasted for approximately 12min with a
      shorter duration in the older group (p<0.02). The cold threshold increased
      significantly (p<0.001), and the warm threshold slightly, after the injection and
      remained high for the whole observation period (i.e. lower and higher
      temperatures were necessary to elicit cold and warmth, respectively). Threshold
      recovery was more delayed in the older age group. Of those 28 ss in whom cold
      pain threshold could be followed during the whole observation period, 18 ss
      showed an immediate threshold decrease of average 6 degrees C which outlasted the
      observation period. Four ss responded with a threshold increase. Heat pain
      thresholds were not affected in the referred pain area. Average synthetic heat
      threshold did not change; there were, however, distinct and lasting individual
      threshold shifts in either direction. Ss with lowered cold pain thresholds or
      evident threshold shifts for synthetic heat had also higher pain ratings. The
      results demonstrate that experimental muscle pain can induce long-lasting changes
      in thermal sensitivity and nociception. The unexpected cold threshold increase
      may tentatively be explained as an expression of long-term depression. The
      decrease of cold pain threshold or SHT in subgroups of ss may indicate central
      sensitization. However, the observed changes in this experiment do not provide an
      unambiguous indicator for central sensitization which seems to be rather
      individual and might depend on pain intensity and proneness to express central
      mechanisms of sensitization. Therefore in clinical pain states the individual
      pattern of sensory abnormalities has to be analysed and interpreted in addition
      to the pain parameters to assess central involvement.

PMID- 12527321
TI  - Induction of non-painful and painful intestinal sensations by hypertonic saline:
      a new human experimental model.
AB  - BACKGROUND AND AIMS: To develop a pain model for chemical stimulation of the
      human gut. METHODS: In a double-blind experimental study 10 subjects with a
      previously performed sigmoidostomy were randomised to receive injections with
      either isotonic or hypertonic saline in the colonic mucosa. In the hypertonic
      experimental arm, 0.1 ml of 0.9%, 2%, 4%, and 6% and 0.2 ml of 2% and 4% saline
      were given. In the placebo arm, six 0.9% saline injections of the same quantities
      were given. In a separate experiment 0.8 ml 4% saline was infused into the mucosa
      by a pump over a period of 2min. The pain intensity was rated on a 0-10 visual
      analogue scale with 5 as the pain threshold. RESULTS: The hypertonic saline
      injections resulted in local as well as referred non-painful and painful
      sensations in 9 out of the 10 subjects. The evoked sensations were mostly
      described as a smarting sensation with an intensity of median 1 (range 0-5.6) for
      0.1 ml 2% saline to median 2.9 (range 0-6.2) for 0.2 ml 4% saline. Seven subjects
      reported referred sensations to the abdominal skin. Continuous infusion of 4%
      saline resulted in a consistent sensory response in all subjects, with a median
      intensity of 4.1 (range 2.1-8.1). This sensory intensity was reproducible in 70%
      in a retest experiment after median 7 weeks. In the placebo arm a total of 70
      isotonic saline injections only resulted in inconsistent, short-lasting non
      painful sensations in three subjects. CONCLUSION: The model represents a safe
      method for direct chemical activation of the sensory endings in the human gut.
      The model may be used for pharmacological screening of analgesics and for basic
      investigations in patients suffering from gastrointestinal diseases.

PMID- 12527322
TI  - Experimental pain by ischaemic contractions compared with pain by intramuscular
      infusions of adenosine and hypertonic saline.
AB  - Deep tissue pain can be related to reduced muscle blood flow, which comprises the
      metabolic demand under muscle work. The tissues and receptors involved in
      nociception after ischaemic muscle contractions are not known. The concentration
      of adenosine is increased after ischaemic contractions and might act as an
      algesic substance. In 15 subjects, adenosine, hypertonic saline (algesic), and
      isotonic mannitol (placebo) were infused into the tibialis anterior muscle and
      compared with the pain caused by ischaemic contractions. The muscle pain
      intensity (visual analogue scale; VAS), distribution, and quality were assessed.
      Pressure pain thresholds were recorded to assess the deep tissue sensitivity.
      Adenosine did not induce more pain than the placebo. The maximal VAS score after
      hypertonic saline and ischaemic contractions was higher compared with
      adenosine/placebo infusions. The duration and area of pain were significantly
      increased after hypertonic saline infusions compared with ischaemic contractions.
      Higher scores on the McGill pain questionnaire were given to the "stabbing",
      "burning", "heavy", and "exhausting" word categories after ischaemic
      contractions, and "cramping" was rated higher during hypertonic saline-induced
      muscle pain compared with ischaemic contractions. During hypertonic saline
      infusions, the pressure pain threshold was decreased compared with before and
      immediately after the pain had vanished. The present study shows that
      pharmacological levels of adenosine in skeletal muscle did not induce pain.
      Excitation of muscle nociceptors by hypertonic saline evoked hyperalgesia, larger
      areas of pain, and a different quality of pain compared with ischaemic
      contractions, suggesting that the pain after ischaemic contractions is mediated
      by other populations of nociceptors in muscle and/or other tissues than excited
      by hypertonic saline.

PMID- 12527323
TI  - Anthrax toxin receptor proteins.
AB  - Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative
      agent of anthrax. Here we discuss what is known about the anthrax toxin receptor
      (ATR), the cellular receptor for anthrax toxin, and how this information is being
      used to develop treatments for anthrax as well as to understand aspects of
      cancer. ATR was identified recently as a type I transmembrane protein with
      unknown function that contains an extracellular integrin-like inserted (I)
      domain. The ATR I domain contains the toxin binding site, and a soluble form of
      this domain was shown to serve as an effective antitoxin to protect cultured
      cells from toxin action. ATR is encoded by the tumor endothelial marker 8 (TEM8)
      gene, which is selectively up-regulated during blood vessel formation and in
      tumor vasculature, raising the possibility that this protein normally functions
      in angiogenesis. Therefore, identification of the cellular receptor for anthrax
      toxin has made possible new avenues of research in the areas of anthrax
      pathogenesis, antitoxin development, and cancer biology.

PMID- 12527324
TI  - Potent inhibition of human folylpolyglutamate synthetase by a phosphinic acid
      mimic of the tetrahedral reaction intermediate.
AB  - A phosphorous-containing pseudopeptide folate analog (Valiaeva et al., J Org Chem
      2001;66:5146-54) was designed to mimic the tetrahedral intermediate formed in the
      ATP-dependent reaction catalyzed by folylpolyglutamate synthetase (FPGS). This
      analog, methotrexate-phosphinate (MTX-phosphinate; 4-amino-4-deoxy-10
      methylpteroyl-L-Glu-gamma-[psi(P(O)(OH)-CH(2))]glutarate), is a highly potent
      (K(is), 3.1+/-0.5 nM), competitive inhibitor of recombinant human cytosolic FPGS.
      Within experimental limits, FPGS inhibition was not time-dependent, and
      preincubation of FPGS, inhibitor, and ATP did not potentiate the inhibition.
      These results suggest that slow phosphorylation to produce a more potent
      inhibitor form is not involved. MTX-phosphinate was not growth inhibitory to
      human CCRF-CEM leukemia cells at 1 microM (70-fold above the concentration of MTX
      giving 50% growth inhibition), probably because of poor transport. Because of its
      exceedingly high potency as an FPGS inhibitor, MTX-phosphinate represents a lead
      structure from which cell-permeable analogs may be developed to test the
      hypothesis that FPGS inhibition is therapeutically efficacious.

PMID- 12527325
TI  - Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through
      a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells.
AB  - Bullatacin, a potential antitumor Annonaceous acetogenin (AA), is isolated from
      the seed of the Formosa Annona atemoya. We reported previously that bullatacin
      inhibits the secretion of hepatitis B surface antigen from 2.2.15 cells (human
      hepatoma HepG2 cells transfected with hepatitis B virus DNA plasmid). In the
      present study, we determined cell apoptosis by using double-dye staining with
      fluorescein-isothiocyanate-labeled annexin V and propidium iodide. We found that
      bullatacin induced apoptosis in 2.2.15 cells in a time-dependent manner; the most
      significant apoptotic change appeared at 16 hr. Moreover, different
      concentrations (10(-3) to 1.0 microM) of bullatacin induced apoptosis in a
      concentration-dependent manner at 16 hr. The determination of intracellular
      cyclic AMP (cAMP) and cyclic GMP (cGMP) levels in 2.2.15 cells after exposure to
      bullatacin demonstrated that bullatacin caused both to decrease in a time- and
      concentration-dependent manner. A time course (0.33, 1, 6, 16, 24hr) study
      indicated that while both cAMP and cGMP levels decreased early (at 0.33 hr), the
      most dramatic decline appeared at 6 hr. Meanwhile, the inhibitory effect on cAMP
      and cGMP levels reached a maximum at 16 hr (90.5+/-3.2 and 47.3+/-12.8%,
      respectively). The concentration-dependent decrease of both cAMP and cGMP induced
      by bullatacin was parallel with the magnitude of apoptosis induced by various
      concentrations (10(-3) to 1.0 microM) of bullatacin. Additionally, the bullatacin
      induced apoptosis was inhibited by the addition of cAMP and cGMP elevating agents
      (forskolin and S-nitrosoglutathione). Our results suggest that a decrease of both
      cAMP and cGMP levels may play a crucial role in bullatacin-induced apoptosis in
      2.2.15 cells.

PMID- 12527326
TI  - Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60
      cells.
AB  - A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of
      capacitative calcium influx through store-operated calcium (SOC) channels. Such
      channels activate after ATP-elicited release of inositol trisphosphate (IP(3))
      sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those
      containing a 4-phenyl group with an electron-withdrawing substituent, such as m-
      or p-nitro- or m-trifluoromethyl (IC(50) values: 3-6 microM). Benzyl esters,
      corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type
      calcium channel blockers, retained potency at SOC channels, as did N-substituted
      DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels
      resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N
      ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L
      type channels. Replacement of the usual 6-methyl group of DHPs with larger
      groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels;
      such DHPs instead elicited formation of inositol phosphates and release of IP(3)
      sensitive calcium stores. Other DHPs also caused a release of calcium stores, but
      usually at significantly higher concentrations than those required for the
      inhibition of capacitative calcium influx. Certain DHPs appeared to cause an
      incomplete blockade of SOC channel-dependent elevations of calcium, suggesting
      the presence of more than one class of such channels in HL-60 cells. N
      Methylnitrendipine (IC(50) 2.6 microM, MRS 1844) and N-propargylnifrendipine
      (IC(50) 1.7 microM, MRS 1845) represent possible lead compounds for the
      development of selective SOC channel inhibitors.

PMID- 12527327
TI  - Cholesteryl-hemisuccinate-induced apoptosis of promyelocytic leukemia HL-60 cells
      through a cyclosporin A-insensitive mechanism.
AB  - We reported previously that alpha-tocopheryl-succinate (VES) induced apoptosis of
      cultured human promyelocytic leukemia cells (HL-60) (Free Radic Res 2000;33:407
      18). We have now studied the effect of cholesteryl-hemisuccinate (CS) on the fate
      of HL-60 cells to clarify whether CS has an effect similar to that of VES. CS
      inhibited the growth of HL-60 cells without differentiation to granulocytes and
      induced DNA fragmentation and ladder formation. CS inhibited the phosphorylation
      of pleckstrin homology domain-containing protein kinase B (Akt) and initiated the
      activation of a caspase cascade. CS triggered the reaction leading to the
      cleavage of Bid and also released cytochrome c (Cyt. c) from mitochondria. In
      addition, CS induced mitochondrial membrane depolarization and translocation of
      Bax to mitochondria in HL-60 cells. However, CS did not induce an increase in the
      concentration of intracellular calcium ions in HL-60 cells. The membrane
      depolarization, Cyt. c release, and DNA fragmentation were inhibited by z-VAD
      fluoromethylketone (z-VAD-fmk), a pan-caspase inhibitor, but not by cyclosporin
      A, an inhibitor of membrane permeability transition. These results suggested that
      CS-induced apoptosis of HL-60 cells might be caused by inhibiting Akt
      phosphorylation following cleavage of Bid through caspase-8 activation and
      subsequently via an Apaf complex-caspase cascade pathway.

PMID- 12527328
TI  - Lipophilicity of analogs of pyridoxal isonicotinoyl hydrazone (PIH) determines
      the efflux of iron complexes and toxicity in K562 cells.
AB  - Iron overload secondary to beta-thalassemia and other iron-loading anemias is the
      most serious obstacle to be overcome in the treatment of these diseases, since
      there is no physiological mechanism for excretion of the excess iron acquired by
      chronic blood transfusion. Due to the inconvenience and cost of the current iron
      chelation therapy, the search for an orally available iron chelator is ongoing.
      Pyridoxal isonicotinoyl hydrazone (PIH) and many of its analogs are effective at
      mobilizing iron in vivo and in vitro at doses that are not toxic. PIH analogs
      were approximately equally effective at binding 59Fe within K562 cells; their
      efficacy depended upon the kinetics of release of the iron-chelator complex from
      the cell, which was correlated inversely with the lipophilicity of the chelators.
      Addition of BSA, which has a well-characterized affinity for lipophilic species,
      to the extracellular medium enhanced iron-chelator efflux, such that all analogs
      caused 59Fe release from the cells as quickly as it was chelated; this suggests
      that BSA acts as an extracellular sink for the iron-chelator complexes, many of
      which are highly lipophilic. The toxicity of the free chelators varied over two
      orders of magnitude, and was correlated with the amount of intracellular 59Fe
      chelator complexes, implicating the complexes in the mechanism of toxicity of the
      chelators. Understanding the structural features that determine the efficacy and
      toxicity of iron chelators in biological systems is of value in the selection of
      PIH analogs for in vivo examination.

PMID- 12527329
TI  - Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3
      kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin
      in breast cells.
AB  - Following observations that curcumin inhibited proliferation (IC(50)=1-5 microM),
      invasiveness and progression through S/G2/M phases of the cell cycle in the non
      tumourigenic HBL100 and tumourigenic MDA-MB-468 human breast cell lines, it was
      noted that apoptosis was much more pronounced in the tumour line. Therefore, the
      ability of curcumin to modulate signalling pathways which might contribute to
      cell survival was investigated. After pre-treatment of cells for 20 min, curcumin
      (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468
      cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and
      2, as well as ERK activity and levels of nuclear c-fos in both cell lines. At a
      lower dose (10 microM), it also inhibited the ability of anisomycin to activate
      JNK, resulting in decreased c-jun phosphorylation, although it did not inhibit
      JNK activity directly. In contrast, the activation of p38 mitogen activated
      protein kinase (MAPK) by anisomycin was not inhibited. Curcumin inhibited basal
      phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more
      consistently and to a greater extent in the MDA-MB-468 cells. The MAPK kinase
      (MKK) inhibitor U0126 (10 microM), while preventing ERK phosphorylation in MDA-MB
      468 cells, did not induce apoptosis. The PI3K inhibitor LY294002 (50 microM)
      inhibited PKB phosphorylation in both cells lines, but only induced apoptosis in
      the MDA-MB-468 line. These results suggest that while curcumin has several
      different molecular targets within the MAPK and PI3K/PKB signalling pathways that
      could contribute to inhibition of proliferation and induction of apoptosis,
      inhibition of basal activity of Akt/PKB, but not ERK, may facilitate apoptosis in
      the tumour cell line.

PMID- 12527331
TI  - The Cl-HCO3- exchanger slows the recovery of acute pHi changes in rat mast cells.
AB  - The CO(2)/HCO(3)(-) buffering system is one of the main mechanisms implicated in
      cytosolic pH (pH(i)) regulation. We studied this pH(i)-regulatory system in rat
      mast cells using a fluorescent dye. Mast cells had a more alkaline pH(i) in the
      presence of HCO(3)(-) than in its absence. The recovery from an acid load was
      faster in HCO(3)(-)-free conditions than in HCO(3)(-)-containing media. In
      HCO(3)(-)-buffered conditions the increase of the recovery rate of an
      acidification in 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-incubated cells
      suggested the implication of a Na(+)-independent Cl(-)/HCO(3)(-) exchanger. This
      HCO(3)(-) transport acidified the cytosol and was also partially responsible for
      the recovery of intracellular alkalinizations. Moreover, regulation of the
      recovery rate of an acidification by protein kinase C and calcium signaling
      pathways depended on the presence or absence of HCO(3)(-). The presence of
      HCO(3)(-) limits the recovery of acute intracellular acidifications probably
      through the Na(+)-independent Cl(-)/HCO(3)(-) exchanger and modulates the
      regulation of pH(i) by protein kinase C and calcium.

PMID- 12527330
TI  - Effects of rhein on human articular chondrocytes in alginate beads.
AB  - This study was designed to investigate the effects of rhein, the active
      metabolite of diacerhein, on the metabolic functions of human chondrocytes
      cultured in alginate beads. Enzymatically isolated osteoarthritic (OA)
      chondrocytes were cultured in alginate beads in a well-defined culture medium for
      12 days. Rhein was tested in a range of concentrations comprised between 10(-7)
      and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin
      (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP
      3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1),
      prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed.
      Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state
      levels were also quantified. In the basal condition, 10(-5)M rhein increased by
      46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3,
      NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased
      IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and
      TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and
      NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up
      regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA
      levels and IL-8 production were not modified by rhein.Overall, these results
      contribute to explain the clinical efficiency of rhein and give new information
      on its mechanisms of action.

PMID- 12527332
TI  - Endothelium-dependent and -independent relaxation and VASP serines 157/239
      phosphorylation by cyclic nucleotide-elevating vasodilators in rat aorta.
AB  - Endothelium-dependent vasodilation is thought to be mediated primarily by the
      NO/cGMP signaling pathway whereas cAMP-elevating vasodilators are considered to
      act independent of the endothelial cell layer. However, recent functional data
      suggest that cAMP-elevating vasodilators such as beta-receptor agonists,
      adenosine or forskolin may also be endothelium-dependent. Here we used functional
      and biochemical assays to analyze endothelium-dependent, cGMP- and cAMP-mediated
      signaling in rat aorta. Acetylcholine and sodium nitroprusside (SNP) induced a
      concentration-dependent relaxation of phenylephrine-precontracted aorta. This
      response was reflected by the phosphorylation of the vasodilator-stimulated
      phosphoprotein (VASP), a validated substrate of cGMP- and cAMP-dependent protein
      kinases (cGK, cAK), on Ser(157) and Ser(239). As expected, the effects of
      acetylcholine were endothelium-dependent. However, relaxation induced by the beta
      receptor agonist isoproterenol was also almost completely impaired after
      endothelial denudation. At the biochemical level, acetylcholine- and
      isoproterenol-evoked cGK and cAK activation, respectively, as measured by VASP
      Ser(239) and Ser(157) phosphorylation, was strongly diminished. Furthermore, the
      effects of isoproterenol were repressed by eNOS inhibition when endothelium was
      present. We also observed that the relaxing and biochemical effects of forskolin
      were at least partially endothelium-dependent. We conclude that cAMP-elevating
      vasodilators, i.e. isoproterenol and to a lesser extent also forskolin, induce
      vasodilation and concomitant cyclic nucleotide protein kinase activation in the
      vessel wall in an endothelium-dependent way.

PMID- 12527333
TI  - beta-Amyloid aggregation induced by human acetylcholinesterase: inhibition
      studies.
AB  - The aggregation of beta-amyloid (1-40) (Abeta) induced by human recombinant
      acetylcholinesterase (HuAChE) was studied by means of circular dichroism (CD) and
      by thioflavin T fluorescence spectroscopy. Abeta was incubated alone and with
      HuAChE. The kinetic of fibrils formation was followed for 48 hr. The increasing
      beta-conformation content induced by HuAChE, preliminary to the formation of
      Abeta fibrils, was determined by circular dichroism. This phenomenon was found to
      be related to the thioflavin T emission of fluorescence at 490 nm. Incubation
      experiments were performed in the presence of known AChE inhibitors
      (physostigmine, edrophonium, decamethonium, propidium) and drugs used for
      Alzheimer's disease (AD) (tacrine, donepezil), to test their capability of
      preventing the HuAChE-induced Abeta aggregation. The non-competitive or mixed
      mode of AChE inhibition was confirmed to be an essential feature. At 100 microM
      propidium, decamethonium, donepezil and physostigmine were found to inhibit the
      HuAChE-induced Abeta aggregation by 82, 25, 22 and 30%, respectively.

PMID- 12527334
TI  - Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7.
AB  - Previous studies have shown that several endogenous compounds, such as bilirubin
      and certain bile acids, are glucosidated in human liver. In this work, we have
      identified human UDP-glucuronosyltransferase 2B7 (UGT2B7) as the isoform that
      catalyzes the glucosidation of hyodeoxycholic acid (HDCA). The glucosidation by
      UGT2B7 was specific for HDCA and was not observed with the other bile acids
      examined, lithocholic acid, chenodeoxycholic acid, and ursodeoxycholic acid. The
      kinetics of HDCA glucuronidation and glucosidation by UGT2B7 were characterized.
      The K(m) values for glucuronidation and glucosidation of HDCA were 11.6 and 17.9
      microM, respectively, with V(max) values of 4.15 nmol/min/mg protein for
      glucuronidation and 3.28 nmol/min/mg for glucosidation. At a fixed concentration
      of HDCA, the apparent K(m) for UDP-glucuronic acid was 89 microM with a V(max) of
      3.53 nmol/min/mg. The corresponding parameters for UDP-glucose were 442 microM
      and 1.98 nmol/min/mg, respectively. UGT2B7 catalyzed the addition of the glucose
      and glucuronic acid moieties to an hydroxyl group on HDCA and also possessed some
      capacity to use UDP-xylose as sugar donor. The two polymorphic variants of
      UGT2B7, UGT2B7(*)1 and UGT2B7(*)2 could both glucosidate HDCA. This is the first
      report that identifies UGT2B7 as the enzyme responsible for the glucosidation of
      the bile acid, HDCA.

PMID- 12527335
TI  - Apoptosis and TRAF-1 cleavage in Epstein-Barr virus-positive nasopharyngeal
      carcinoma cells treated with doxorubicin combined with a farnesyl-transferase
      inhibitor.
AB  - Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas (NPC) are much more
      sensitive to chemotherapy than other head and neck carcinomas. Spectacular
      regressions are frequently observed after induction chemotherapy. However, these
      favorable responses are difficult to predict and often of short duration. So far
      there have been only few experiments to investigate the mechanisms which
      underline the cytotoxic effects of anti-neoplastic drugs against NPC cells. In
      addition, these studies were performed almost entirely on EBV-negative cell lines
      therefore not truly representative of NPC cells. For the first time, we have used
      two EBV-positive NPC tumor lines derived from a North African (C15) and a Chinese
      (C666-1) patient as in vitro targets for a panel of anti-neoplastic agents.
      Doxorubicin, taxol and in a lesser extent cis-platinum efficiently inhibited NPC
      cell proliferation at clinically relevant concentrations, but all three agents
      failed to induce apoptosis. However, massive apoptosis of C15 cells was achieved
      when doxorubicin (1 microM) was combined with a farnesyl-transferase inhibitor,
      BIM 2001 (5 microM). Moreover, this apoptotic process was associated with a
      caspase-dependent early cleavage of the TNF-receptor associated factor 1 (TRAF-1)
      molecule, a signaling adaptor which is specifically expressed in latently EBV
      infected cells. TRAF-1 cleavage might become a useful indicator of chemo-induced
      apoptosis in EBV-associated NPCs.

PMID- 12527336
TI  - Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant
      dopamine vs. serotonin receptor subtypes.
AB  - Animal studies indicate that the anxiolytic properties of the antipsychotic agent
      cyamemazine may result from blockade of serotonin 5-HT(2C) receptors and to a
      lesser extent from blockade of serotonin 5-HT(3) receptors. Here, we used human
      recombinant receptors to determine the relative affinity of cyamemazine for
      serotonin and dopamine receptor subtypes. In addition, cyamemazine was tested in
      other brain receptor types and subtypes which are considered to mediate central
      nervous systems effects of drugs. Hence, cyamemazine affinity was determined in
      human recombinant receptors expressed in CHO cells (hD(2), hD(3), and hD(4.4)
      receptors, h5-HT(1A), h5-HT(2A), h5-HT(2C), and h5-HT(7), and hM(1), hM(2),
      hM(3), hM(4), and hM(5) receptors), L-cells (hD(1) receptor), and HEK-293 cells
      (h5-HT(3) receptors) or natively present in N1E-115 cells (5-HT(3) receptors) or
      in rat cerebral cortex (non-specific alpha(1)- and alpha(2)-adrenoceptors,
      GABA(A) and GABA(B) receptors, H(3) histamine receptors), and guinea-pig
      cerebellum (H(1) central and H(2) histamine receptors) membranes. Similarly to
      atypical antipsychotics, cyamemazine exhibited high affinity for: (i) h5-HT(2A)
      receptors (K(i)=1.5+/-0.7 nM, mean+/-SEM, N=3) and this was four times higher
      than for hD(2) receptors (K(i)=5.8+/-0.8 nM), (ii) h5-HT(2C) receptors
      (K(i)=11.8+/-2.2nM), and (iii) 5-HT(7) receptors (K(i)=22 nM). Conversely,
      cyamemazine exhibited very low affinity for h5-HT(3) receptors (K(i)=2.9+/-0.4
      microM). In conclusion, similarly to atypical antipsychotic agents, cyamemazine,
      possesses high affinity for h5-HT(2A), h5-HT(2C), and h5-HT(7) receptors, a
      feature which can explain its low propensity to cause extrapyramidal adverse
      reactions in clinical practice. The high affinity for h5-HT(2C) receptors, but
      not for h5-HT(3) receptors, can account for the anxiolytic activity of
      cyamemazine in human subjects.

PMID- 12527337
TI  - Effect of genotype on steady-state CYP1A1 gene expression in human peripheral
      lymphocytes.
AB  - We have analyzed the steady-state levels of cytochrome P-450 1A1 (CYP1A1) mRNA in
      peripheral blood lymphocytes of 177 individuals with various CYP1A1 genotypes
      using a quantitative reverse transcriptase-polymerase chain reaction technique
      that makes use of a homologous internal standard for accurate quantitation. We
      found no effects of ethnicity, age, or smoking status on CYP1A1 gene expression
      in this population. We did see a significant 2-fold increase in the mean level of
      CYP1A1 mRNA in women compared with men for both Caucasians and African Americans.
      We observed no effect of the African American-specific polymorphism (CYP1A1(*)3)
      on expression of the gene. However, we found a significant 3-fold decrease in
      expression associated with the homozygous MspI restriction fragment length
      polymorphism (CYP1A1(*)2A/(*)2A).

PMID- 12527338
TI  - Probing the binding of the flavonoid, quercetin to human serum albumin by
      circular dichroism, electronic absorption spectroscopy and molecular modelling
      methods.
AB  - The plant derived flavonoid compound quercetin, possesses wide range of
      biological activities in the human body by interacting with nucleic acids,
      enzymes and other proteins. As has recently been shown this molecule of
      polyphenolic type extensively binds to human serum albumin (HSA), the most
      abundant carrier protein in the blood. Electronic absorption, circular dichroism
      (CD) spectroscopy and molecular modelling methods were used to characterize
      optical properties of the quercetin-HSA complex, and to gain information on the
      binding mechanism at molecular level. The red shift and hypochromism of the
      longest-wavelength absorption band of quercetin relative to the spectral
      properties in ethanol suggests that one or more phenolic OH groups of the bound
      ligand is ionized and that the exocyclic phenyl ring is not coplanar with the
      benzopyrone moiety. It was found that quercetin shows extrinsic optical activity
      on interaction with HSA. The induced CD spectra were utilized to calculate the
      association constant at 37 degrees (1.46+/-0.21 x 10(4)M(-1)) and to probe the
      ligand binding site. Results of the CD displacement experiments performed with
      palmitic acid and salicylate were interpreted together with the findings of
      molecular modelling calculation performed on the quercetin-HSA complex.
      Computational mapping of possible binding sites of quercetin revealed the
      molecule to be bound in the large hydrophobic cavity of subdomain IIA. The
      protein microenvironment of this site was found to be rich in polar (basic) amino
      acid residues which are able to help to stabilize the negatively charged ligand
      bound in non-planar conformation. Additionally, the position of quercetin within
      the binding pocket allows simultaneous binding of other ligands such as warfarin,
      or sodium salycilate.

PMID- 12527339
TI  - Suppression of tumor necrosis factor-alpha and inducible nitric oxide synthase
      gene expression by THI 52, a new synthetic naphthyl-benzylisoquinoline alkaloid.
AB  - The effects of THI 52 (1-naphthylethyl-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline) on (a) inducible nitric oxide synthase (iNOS) and tumor
      necrosis factor-alpha (TNF-alpha) expression in RAW 264.7 cells stimulated by
      lipopolysaccharide (LPS)/interferon gamma (IFN-gamma), (b) plasma nitrate
      concentration as well as iNOS protein expression (lung) in vivo in LPS-treated
      rats, and (c) the restoration of vascular contractility to vasoconstrictor agents
      in LPS-treated vessels in vitro were investigated. THI 52 concentration
      dependently reduced not only nitric oxide (NO) production (IC(50) value, 12.5
      microM) but also the expression of TNF-alpha and iNOS mRNA in RAW 264.7 cells.
      Incubation of rat endothelium-denuded thoracic aorta with LPS (300 ng/mL) in
      vitro for 8 hr resulted in the suppression of vasoconstrictor effects to
      phenylephrine (PE), effects that were restored by co-incubation with THI 52.
      Administration of THI 52 (10 and 20mg/kg, i.p.) 30 min before injection of LPS
      (10mg/kg, i.p.) resulted in a significant reduction of the expression of iNOS
      protein in rat lung tissue and in the plasma nitrite/nitrate (NOx) level.
      Addition of THI 52-treated macrophage-conditioned medium to a TNF-sensitive L929
      fibroblast cell line (CCL1) increased cell viability, depending on the
      concentration of THI 52. Finally, THI 52 inhibited the activation of nuclear
      factor kappaB (NF-kappaB) by inhibition of IkappaB degradation through the
      prevention of IkappaB phosphorylation. Collectively, these results strongly
      suggest that THI 52 suppresses both TNF-alpha and iNOS gene expression by
      inhibiting NF-kappaB. Thus, THI 52, a new synthetic isoquinoline alkaloid, may be
      beneficial in inflammatory disorders where the overproduction of NO and TNF-alpha
      is a matter of concern.

PMID- 12527340
TI  - Dimethylsphingosine increases cytosolic calcium and intracellular pH in human T
      lymphocytes.
AB  - N,N-Dimethyl-D-erythro-sphingosine (DMS) is the N-methyl derivative of
      sphingosine; both are activators of sphingosine-dependent protein kinases. The
      aim of this work was to study the effect of DMS on cytosolic calcium and
      intracellular pH (pHi) in human T lymphocytes. The variations of calcium and pH
      were determined by fluorescence digital imaging using Fura-2-AM and BCECF-AM,
      respectively. DMS increased both pHi and Ca(2+)-cytoslic in human T lymphocytes.
      These effects were dose-dependent. This drug induced a fast increase in pHi and a
      release of calcium from different intracellular calcium pools than thapsigargin.
      DMS also induced a Ca(2+)-influx different from the store-operated calcium
      channels, since drug effect was not modified by 30 microM SKF 96365. The influx
      of calcium induced by DMS was completely blocked by preincubation in the presence
      of nickel, or lanthanum, while the increase in pHi was no affected. However, the
      presence of cadmium reduced but does not block Ca(2+)-influx. The inhibition of G
      protein by 100 ng/mL pertussis toxin, and the inhibition of tyrosine kinases by
      genistein significantly reduced the cytosolic calcium increase induced by DMS by
      an inhibition of both, release of calcium from intracellular pools and influx
      from extracellular medium. The inhibition of pools emptiness by these drugs was
      related with the inhibition that they induce in the DMS cytosolic alcalinization.
      In summary, DMS increases pHi and as consequence releases calcium from
      intracellular pools, and it increases calcium-influx through a channel different
      from store-operated channel (SOC). Both cytosolic calcium and pHi increase are
      modulated by G-proteins and tyrosine kinases.

PMID- 12527341
TI  - Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic
      model: the role of human beta-glucuronidase, sulfotransferase, catechol-O
      methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism.
AB  - Quercetin-3- and quercetin-7-glucuronides are major products of small intestine
      epithelial cell metabolism (J. Nutr. 130 (2000) 2765) but it is not known if
      quercetin glucuronides can be further processed in the liver or if they are
      excreted directly. Using the HepG2 hepatic cell model, we show that highly
      purified quercetin-7- and quercetin-3-glucuronides can follow two pathways of
      metabolism: (i) methylation of the catechol functional group of both quercetin
      glucuronides (44% of quercetin-7-glucuronide at a rate of 2.6 nmol/hr/10(6)
      cells, and 32% of quercetin-3-glucuronide at a rate of 1.9 nmol/hr/10(6) cells,
      over 48 hr) or (ii) hydrolysis of the glucuronide by endogenous beta
      glucuronidase followed by sulfation to quercetin-3'-sulfate (7% of quercetin-7
      glucuronide at a rate of 0.42 nmol/hr/10(6) cells and 10% of quercetin-3
      glucuronide at a rate of 0.61 nmol/hr/10(6) cells, over 48 hr). In contrast,
      quercetin-4'-glucuronide was not metabolised, and interestingly this is not a
      major product of the small intestine absorption process. The conversion of the
      quercetin-7- and quercetin-3-glucuronide to the mono-sulfate conjugate shows
      intracellular deglucuronidation by beta-glucuronidase activity, allowing
      transient contact of the free aglycone with the cellular environment. Inhibition
      of methylation using a catechol-O-methyltransferase inhibitor shifted metabolism
      towards sulfation, as indicated by an increase in quercetin-3'-sulfate formation
      (increase in rate to 1.13 and 1.43 nmol/hr/10(6) cells for quercetin-7
      glucuronide and quercetin-3-glucuronide, respectively). Efflux of quercetin
      metabolites from HepG2 cells (methylated glucuronide and sulfate conjugates) was
      not altered by verapamil, a p-glycoprotein inhibitor, but efflux was
      competitively inhibited by MK-571, a multidrug resistant protein inhibitor,
      indicating a role for multidrug resistant protein in the efflux of quercetin
      conjugates from HepG2 cells. These results show that HepG2 cells can absorb and
      turnover quercetin glucuronides and that human endogenous beta-glucuronidase
      activity could modulate the intracellular biological activities of dietary
      antioxidant flavonoids.

PMID- 12527342
TI  - Laparoscopic adjustable gastric banding in bariatric surgery: an overview of the
      LAP-BAND. Introduction.

PMID- 12527343
TI  - The extent of the problem of obesity.
AB  - The prevalence of obesity is increasing worldwide. In the United States, in 1999,
      27% of adults had a body mass index >30 kg/m(2), almost double the prevalence of
      20 years earlier. The estimated mortality from obesity-related diseases in the
      United States is approximately 300,000 annually and growing. In the future,
      mortality related to obesity is expected to exceed that of smoking. Numerous
      diseases are caused or made worse by obesity. These include type 2 diabetes;
      hypertension; dyslipidemia; ischemic heart disease; stroke; obstructive sleep
      apnea; asthma; nonalcoholic steatohepatitis; gastroesophageal reflux disease;
      degenerative joint disease of the back, hips, knees, and feet; infertility and
      polycystic ovary syndrome; various malignancies; and depression. Type 2 diabetes
      is perhaps the most visible obesity-related problem. Present in at least 14
      million Americans, it leads to serious complications and premature death. It is
      largely caused by obesity, and is generally cured by weight loss. The quality of
      life of the obese is markedly reduced, and the costs to health care systems are
      great. Preventive programs have yet to affect the rising prevalence. An effective
      solution is needed.

PMID- 12527344
TI  - Medical and surgical options in the treatment of severe obesity.
AB  - Weight loss programs, diets, and drug therapy have not shown long-term
      effectiveness in treating morbid obesity. A 1992 statement from the National
      Institutes of Health Consensus Development Conference affirmed the superiority of
      surgical over nonsurgical approaches to this condition. Bariatric surgical
      procedures work in 1 of 2 ways: by restricting a patient's ability to eat
      (restrictive procedures) or by interfering with ingested nutrient absorption
      (malabsorptive procedures). Many of these procedures can be performed by a
      laparoscopic approach, which has been shown to reduce operative morbidity. In the
      United States, the primary operative choice for morbidly obese patients has
      recently shifted from vertical banded gastroplasty (VBG) to the Roux-en-Y gastric
      bypass (RYGBP). VBG, a purely restrictive procedure, has fallen into disfavor
      because of inadequate long-term weight loss. RYGBP combines restriction and
      malabsorption principles, and has been shown to induce greater weight loss than
      VBG. Other procedures currently being offered include laparoscopic adjustable
      gastric banding; biliopancreatic diversion (BPD), including the duodenal switch
      (BPD-DS) variation; and distal gastric bypass (DGBP). Laparoscopic adjustable
      gastric banding with the LAP-BAND system (INAMED Health, Santa Barbara, CA), a
      restrictive procedure involving placement of a silicone band around the upper
      stomach, was introduced in the early 1990s and approved by the US Food and Drug
      Administration for use in the United States in June 2001. Outside the United
      States, LAP-BAND surgery is the most commonly performed operation for severe
      obesity. The BPD, BPD-DS, and DGBP are all malabsorptive procedures offered
      primarily by laparotomy. They have been shown to induce good long-term weight
      loss but have a higher rate of adverse nutritional complications. Many safe and
      effective surgical options for severe obesity are available. More scientific
      appraisals comparing different procedures and open and laparoscopic approaches
      are needed.

PMID- 12527345
TI  - Selecting the optimal patient for LAP-BAND placement.
AB  - Optimal patient selection for laparoscopic adjustable gastric banding with the
      LAP-BAND (INAMED Health, Santa Barbara, CA) enables maximization of results for
      patients most suited to the procedure and avoidance of unsatisfactory outcomes
      for inappropriate candidates. We have investigated potential predictors of
      outcomes in our patients to look for associations with weight loss. We have also
      reviewed published data for additional predictors. This analysis has revealed a
      number of conditions associated with a significantly lower percent excess weight
      loss (%EWL) than experienced in the overall group. These include increasing age,
      increasing body mass index (BMI), hyperinsulinemia, insulin resistance, type 2
      diabetes, and polycystic ovary syndrome. There was also less weight loss if the
      SF-36 quality-of-life measure showed a poor physical activity score, high pain
      score, or poor general health score. However, in all these conditions, the effect
      was small in comparison with the benefits achieved by these patients, and was
      judged insufficient to preclude this approach to treatment of their obesity. A
      number of conditions were found to have no relation to weight loss after LAP-BAND
      placement. These included sex, presence of mental illness, most comorbidities
      except those linked to insulin resistance, previous bariatric surgery, and sweet
      eating behavior. The value of psychologic assessment to predict outcomes could
      not be established. The superobese (BMI >50) achieved a lower %EWL at 1 year
      after LAP-BAND placement compared with those with BMI <50, but there were no
      differences at the 2-, 3-, and 4-year follow-ups.

PMID- 12527346
TI  - Evolution of a paradigm for laparoscopic adjustable gastric banding.
AB  - The first human laparoscopic adjustable gastric banding procedure, using the LAP
      BAND device (INAMED Health, Santa Barbara, CA), was performed on September 1,
      1993. Because of its minimal invasiveness, reversibility, and adjustability, it
      is considered a breakthrough in bariatric surgery. Placement of the LAP-BAND is
      the least invasive operative procedure that can be offered to patients with
      morbid obesity. The technique has evolved since it was first performed on humans.
      This evolution mainly concerns the band's position in relation to the gastric
      wall, which necessitated modifying the posterior dissection for band passage and
      placement. These technical changes have been aimed at reducing morbidity,
      especially the major complication, prolapse/slippage or pouch dilatation above
      the band. Based on personal experience and a review of the literature, the
      authors describe how the surgical technique has developed since the introduction
      of the LAP-BAND. The advantages of the LAP-BAND have contributed to its
      increasing use throughout the world. The authors believe that the approach
      represents a paradigm shift in bariatric surgery.

PMID- 12527347
TI  - A step-by-step guide to placement of the LAP-BAND adjustable gastric banding
      system.
AB  - The early promise of laparoscopic adjustable gastric banding was tempered by
      reports of high rates of gastric herniation or prolapse. These complications are
      a function of the operative technique used early on. At the time, in the early
      1990s, the LAP-BAND device (INAMED Health, Santa Barbara, CA) was placed lower on
      the stomach, near the first short gastric vessel. The required perigastric
      dissection was difficult and variable in its extent, depending on the width of
      the stomach and where the surgeon began the dissection. To combat these problems,
      a new surgical method for placement of the band has evolved. Called the pars
      flaccida technique, it emphasizes minimal dissection and placement of the LAP
      BAND out of the lesser sac. This leads to a higher position of the band, away
      from the body of the stomach. The technique serves to make band placement simple,
      safe, reproducible, and easily teachable, as well as to decrease the rate of
      gastric herniation or prolapse. Keeping the band out of the lesser sac, away from
      the peristalsing stomach, minimizing dissection of the attachments to the
      stomach, paying strict attention to gastric-to-gastric suturing, and leaving all
      fluid out of the band until at least 6 weeks after surgery appear to be the most
      important factors in reducing the incidence of this complication.

PMID- 12527348
TI  - Avoiding postoperative complications with the LAP-BAND system.
AB  - The most frequently occurring complications associated with the LAP-BAND (INAMED
      Health, Santa Barbara, CA) include gastric prolapse, stoma obstruction,
      esophageal and gastric pouch dilatation, erosion, and access port problems. This
      article describes the causes of these complications and details some points for
      their prevention and treatment. As techniques for placement of the LAP-BAND have
      evolved, complication rates have declined. For example, occurrence of gastric
      prolapse was reduced from the initially reported rates of 22% to less than 5%.
      The emergence of many problems, such as gastric pouch dilatation or prolapse, can
      be minimized with proper operative technique and close postoperative management
      and follow-up. As with other major surgical procedures, particularly those
      performed in the bariatric population, complications associated with the LAP-BAND
      system are unavoidable but are rarely life-threatening if managed appropriately.
      Surgeons and patients should adopt strategies that will help avoid complications
      and be sensitive to any indication of their emergence.

PMID- 12527349
TI  - Patient management after LAP-BAND placement.
AB  - Severe obesity is a chronic disease requiring continuing care. Optimal outcomes
      of laparoscopic adjustable gastric banding using the LAP-BAND (INAMED Health,
      Santa Barbara, CA) depend on accurate placement of the band and excellent
      postplacement care, which requires a long-term commitment from both the patient
      and the bariatric surgical team. Adjustability is a key feature of the LAP-BAND
      system, and knowing when and how much to adjust requires careful judgment. Two
      methods of approaching the art of adjustment are described: the office adjustment
      and the radiologic adjustment. A properly placed and adjusted band produces
      prolonged satiety after a small meal, facilitating a major reduction in dietary
      intake leading to weight loss. Healthy food choices, increased activity and
      exercise, and the behavioral changes necessary to achieve these are essential
      elements of all weight loss programs. The LAP-BAND program is no exception.
      Follow-up requires monitoring of the comorbidities of obesity and metabolic and
      nutritional status. Communication and collaboration with the patient's primary
      care provider are important. All of the elements above are necessary to provide
      the comprehensive care that contributes to optimal patient outcomes.

PMID- 12527350
TI  - Weight loss and early and late complications--the international experience.
AB  - Following its introduction in 1993, the LAP-BAND (INAMED Health, Santa Barbara,
      CA) has been used extensively across the world for the treatment of obesity, and
      data on safety and effectiveness are now available. This review draws on the
      literature and our own clinical patient base to provide an overview of the early
      and late problems associated with LAP-BAND placement and its effects on weight
      loss. It has proved to be a remarkably safe procedure. A report analyzing
      international data on laparoscopic adjustable gastric bands identified 3 deaths
      in 5,827 patients (approximately 1 in 2,000). In our series of 1,120 patients,
      there have been no deaths and no life-threatening perioperative complications.
      Significant early complications occurred in 17 (1.5%) of our patients; late
      problems have been more common, particularly during our early experience.
      Prolapse of the stomach through the band occurred in 125 (25%) of our first 500
      patients but has occurred in only 28 (4.7%) of our last 600 patients. Erosion of
      the band into the stomach occurred in 34 patients (3%); all occurred in the first
      500 patients. No erosions have occurred in the last 600 patients. Both problems
      are treated laparoscopically by removal and replacement. Combined international
      data show that weight loss after LAP-BAND placement is characterized by steady
      progressive weight loss over a 2- to 3-year period, followed by stable weight out
      to 6 years. This pattern reflects the benefit of adjustability. For the
      international series, the percent excess weight loss (%EWL) at 2 years has been
      between 52% and 65%. In our series, %EWL at 5 years and 6 years was 54% and 57%,
      respectively. The LAP-BAND is proving to be extremely safe, able to facilitate
      good weight loss, and able to maintain weight loss over time.

PMID- 12527353
TI  - How (not) to give a seminar.

PMID- 12527351
TI  - US experience with the LAP-BAND system.
AB  - Laparoscopic adjustable gastric banding is the most commonly performed operation
      for morbid obesity in Europe and Australia and has been shown to result in
      significant long-term weight loss. The US Food and Drug Administration (FDA)
      monitored clinical trial results with the LAP-BAND system (INAMED Health, Santa
      Barbara, CA) did not reproduce the results of studies performed elsewhere in the
      world. This article reviews data from the first and second FDA clinical trials as
      well as data from continuing US clinical experience. Four American surgeons at 4
      centers have performed more than 500 LAP-BAND procedures not included in the
      first 2 FDA clinical trials. Of these patients, 115 have been followed for at
      least 9 months, and 43 have been followed for at least 12 months. A retrospective
      analysis of prospective data gathered from these patients is presented. The
      percent excess weight loss was 35.6% at 9 months and 41.6% at 12 months. The
      average body mass index decreased from 47.5 to 38.8 in 9 months and from 47.5 to
      37.3 in 12 months. There were no deaths related to the insertion of the device.
      Of 15 complications requiring operative management (13%) in 12 patients, there
      were 8 port displacements or tubing breaks (7%), 2 elective explantations (2%), 2
      cases of gastric prolapse (2%), 1 gastric pouch dilatation (<1%), 1 port abscess
      (<1%), and 1 hemorrhage (<1%). Clinical experience with the LAP-BAND system in
      the United States shows the device to be a safe and effective treatment for
      morbid obesity, with results comparable to the international data. The
      combination of proper surgical technique and close patient follow-up with
      frequent band adjustments, performed in a comprehensive bariatric program
      setting, may make the LAP-BAND system a powerful surgical tool in the treatment
      of morbid obesity.

PMID- 12527352
TI  - Changes in comorbidities and improvements in quality of life after LAP-BAND
      placement.
AB  - Possibly the most important outcomes of bariatric surgery involve changes in
      obesity-related illness, quality of life (QOL), and psychologic well-being.
      Dramatic improvement or resolution of serious medical comorbidity accompanies the
      weight loss following laparoscopic adjustable gastric banding with the LAP-BAND
      (INAMED Health, Santa Barbara, CA). There are major improvements in the
      conditions of the metabolic syndrome, which is characterized by impaired glucose
      tolerance, dyslipidemia, and hypertension. Improvement in insulin sensitivity and
      pancreatic beta-cell function associated with weight loss induces remission in
      the majority of type 2 diabetics and reduces the risk of others developing type 2
      diabetes. Improvement in dyslipidemia is characterized by raised high-density
      lipoprotein cholesterol and lower triglyceride concentrations. Together with
      lower blood pressure, these changes provide a substantial reduction in
      cardiovascular risk. Other medical conditions caused or aggravated by obesity are
      also significantly improved, including sleep apnea, daytime sleepiness, asthma,
      and gastroesophageal reflux. Weight loss is associated with improved fertility
      and more favorable pregnancy outcomes. All aspects of QOL improve substantially,
      especially physical disability, and post-weight-loss QOL measures approximate
      those of the general population. There are also major improvements in body image
      and reduction in depressive illness. These changes provide perhaps the most
      compelling data regarding the value of LAP-BAND surgery and underlie the great
      satisfaction experienced by patients.

PMID- 12527354
TI  - Is tensegrity a unifying concept of protein folds?
AB  - We suggest that the three-dimensional architecture of globular proteins can be
      described in terms of tensegrets, i.e. structural elements that are held together
      through attractive and repulsive forces. Hard elements of tensegrets are
      represented by secondary structure elements, i.e. alpha-helices and beta-strands,
      while the role of elastic elements is played by attractive and repulsive atomic
      forces. Characteristics of tensegrets is that they can auto-assemble and that
      they respond to changes of tension in some part of the entire object through a
      deformation in another part, thus partially preserving their structure, despite
      their deformation. This latter property well explains both the folding process
      and the behavior of globular proteins under mild denaturing conditions, as
      revealed by the molten globule state.

PMID- 12527355
TI  - Cell adhesion molecule regulation of nucleocytoplasmic trafficking.
AB  - Cells undergo processes such as proliferation, differentiation, and survival
      based upon cues that they receive from their microenvironment. Extracellular
      matrix adhesion molecules, such as integrins and syndecans, and cell-cell
      adhesion molecules, including cadherins and Ig superfamily members, convey
      information about the environment to the cell. It is evident that cell adhesion
      molecules (CAMs) regulate a variety of signaling events. An emerging theme is
      that one level of CAM signaling control is through regulated nucleocytoplasmic
      distribution of molecules that either phosphorylate or co-activate transcription
      factors. In this manner, CAMs control transcription events that ultimately have a
      strong impact on cellular processes.

PMID- 12527356
TI  - Sequence anatomy of mitochondrial anion carriers.
AB  - Two hundred and eighty-four genes of eight eukaryotic genomes for mitochondrial
      anion carriers were sorted into 43 (+18 single protein) subfamilies. Subfamilies
      differ by the number, nature, and locations of charges and polar residues in the
      transmembrane alpha-helices. Consequently, these residues and the rarely unique
      residues of the matrix and cytosolic segments most likely determine the different
      molecular phenotypes (functions). 'Common ancestral hydrophilic segments' were
      found in matrix and cytosolic segments, with interchangeable polar residues. Thus
      the hydrophobic microstructures of hydrophilic carrier parts are supposed to
      predetermine structure/conformation, whereas polar and charged microstructures
      should predetermine function, namely in the transmembrane spanning alpha-helices.